PMID- 28488478
TI  - Student life - How to fix the leaky bucket: investing in nurse education.
AB  - Education is key to fixing 'the leaky bucket', where more nurses are leaving the
      profession than joining it, says a specialist RCN group.

PMID- 28488477
TI  - The fine art of diversion.
AB  - What about the NHS?' says Jeremy. 'Things are getting to breaking point, and I
      mean breaking point.'

PMID- 28488479
TI  - Readers' panel - Will the Nurse First programme improve recruitment?
AB  - Our experts consider a hot topic of the day.

PMID- 28488480
TI  - Prime minister fails to comment on nurses having to turn to food banks.
AB  - Nursing leaders have criticised the prime minister for failing to explicitly say
      whether it is wrong that nurses in the UK have to use food banks.

PMID- 28488482
TI  - Staff handovers at bedside allow more time for patient care.
AB  - Staff in an emergency assessment unit at an NHS hospital have introduced bedside
      nurse handovers to promote interaction with patients.

PMID- 28488484
TI  - 'Wonderful and courageous nurse' is Patient's Choice.
AB  - Joanna O'Toole has won the 2017 Patient's Choice category of the RCNi Nurse
      Awards 2017 - the only category to be decided by a vote open to the general
      public.

PMID- 28488485
TI  - Staff praised for help after stabbing.
AB  - Two hospice nurses have been commended for coming to the aid of a woman who was
      stabbed in a knife attack.

PMID- 28488486
TI  - Letter.
AB  - I don't like bedside handovers. You can't say everything in front of the patient
      or in front of the other patients, or their relatives, and it would take longer.
      At the end of your shift all you want to do is go home on time.

PMID- 28488487
TI  - Too much direction.
AB  - So NHS England is to employ two more directors of nursing (news, 26 April).
      Presumably this will require the employment of at least two more admin staff and
      minions. Total cost? About L200,000 a year? Or about six or seven nurses, just
      the amount most wards seem to be short of.

PMID- 28488488
TI  - The widening gap.
AB  - Differences between the employment situation of NHS nurses working in Scotland
      and England are becoming ever more pronounced. This was reinforced recently in
      the report from the NHS Pay Review Body (RB) on staff pay in Scotland.

PMID- 28488489
TI  - Increase in number of senior BME nurses and midwives is great news.
AB  - In March, NHS England published the second Workforce Race Equality Standard
      (WRES) data analysis report. This analyses the differences in experience of black
      and minority ethnic (BME) and white staff in the NHS, across nine WRES
      indicators.

PMID- 28488491
TI  - The bored room.
AB  - Liverpool Heart and Chest Hospital does not charge for TV or wifi (news online, 3
      May). It's all free. And patients can use the phone at the nurses' station.

PMID- 28488490
TI  - How to attract a male.
AB  - In Malcolm Harrison's response (letters, 26 April) to Andrew Haydon's article
      'Where are all the male nursing students?' (students, 12 April), he asks why men
      aren't being provided with the same support as other minority groups.

PMID- 28488492
TI  - It's time for action.
AB  - We all need to strike together: Unison and all nursing union members (readers'
      panel, 3 May). But, being nurses, the strike would last less than an hour.

PMID- 28488494
TI  - Why RCN Nurse of the Year is such an inspiring winner.
AB  - Remember the name: Melanie Davies, RCN Nurse of the Year 2017 and a truly
      extraordinary woman. She has transformed care for people with learning
      disabilities on her ward, driven through changes across her hospital and health
      board in south Wales, and inspired others to follow suit across the country.

PMID- 28488495
TI  - Profession's finest honoured at awards.
AB  - The innovation, talent and skill of the UK's nursing profession was celebrated at
      the RCNi Nurse Awards 2017 last week. The winners were announced at a glittering
      evening ceremony at the Westminster Park Plaza Hotel in London on 5 May.

PMID- 28488496
TI  - Action Research for Nurses McDonnell Peter and McNiff Jean Action Research for
      Nurses 192pp L24.99 Sage 9781473919402 1473919401 [Formula: see text].
AB  - The two authors of this long-overdue book offer a cogent critique of the current
      body of nursing and research knowledge guided by three basic questions: what
      constitutes nursing knowledge, how is knowledge acquired and how is this
      knowledge put to use?

PMID- 28488497
TI  - The Essentials of Nursing Leadership Taylor Ruth and Webster-Henderson Brian The
      Essentials of Nursing Leadership 216pp L22.99 Sage Publishing 9781412962025
      1412962021 [Formula: see text].
AB  - All aspects of leadership are covered in this excellent book. The first part
      focuses on theory of leadership, and the second on necessary skills, approaches
      and styles.

PMID- 28488498
TI  - 'Always be true to your values'.
AB  - Helene Donnelly qualified as a nurse in 2002 and became a nurse practitioner in
      the emergency department at Stafford Hospital in 2005. After becoming concerned
      about poor patient care, she raised more than 100 complaints and was a key
      witness at the inquiry into care failings at Mid Staffordshire NHS Foundation
      Trust. She took up her current role as ambassador for cultural change at
      Staffordshire and Stoke on Trent Partnership NHS Trust in 2013, and was awarded
      an OBE for services to the health service the same year.

PMID- 28488499
TI  - Nursing shortages: how bad will it get?
AB  - The NHS in England has 24,000 vacancies for nurses, leaving many trusts with more
      than 200 posts vacant. But the cumulative impact of a number of factors - from an
      ageing workforce and pay restraint to Brexit - could make staff shortages a great
      deal worse in the near future.

PMID- 28488500
TI  - IV cannula site management.
AB  - What was the nature of the CPD activity, practice-related feedback and/or event
      and/or experience in your practice? The article discussed management of
      intravenous (IV) cannula sites, including cannula insertion, care of the device
      and potential complications related to cannula use.

PMID- 28488501
TI  - Scotland's new mental health strategy.
AB  - Essential facts The Scottish Government has unveiled a ten-year mental health
      strategy.

PMID- 28488502
TI  - Parents may not want children vaccinated against influenza.
AB  - Parents who generally support vaccination may doubt the necessity of an influenza
      vaccination for their child, research suggests.

PMID- 28488504
TI  - Meet the RCN Nurse of the Year 2017.
AB  - 'Never again on my ward, in my hospital, on my health board; that's what I
      resolved and I felt it in my heart,' says RCN Nurse of the Year 2017 Melanie
      Davies. 'I have driven it and made it real. I made a promise to Paul's family
      that no other patient or family would experience the care that he sadly
      received.'

PMID- 28488503
TI  - Pre-surgery fitness programme reduces patients' stay in hospital.
AB  - Patients who 'train' their body before undergoing surgery spend less time in
      hospital and have reduced medical costs, a US study has found.

PMID- 28488507
TI  - How to assist patients with sit-stand transfers.
AB  - Rationale and key points This article discusses optimal methods for assisting
      patients with sit-stand transfers where moving-and-handling equipment is not
      required. The article explains the importance of effective mobility care in
      optimising patients' rehabilitation and enhancing their independence. " The term
      'assistance' is used in this article to refer to the support nurses can provide
      to patients during sit-stand transfers, but excludes manual assistance. Nurses
      should attempt various 'hands-off' mobility-enhancing strategies to assist the
      patient, such as the use of verbal, visual or light manual cues. " There are
      three main considerations when assisting patients with sit-stand transfers:
      maintaining the safety of the patient and healthcare staff; optimising the
      patient's mobility; and the use of a person-centred approach to care. " It is
      important to ensure the correct biomechanics of sit-stand transfers are followed
      during these procedures. Reflective activity 'How to' articles can help you
      update your practice and ensure it remains evidence-based. Apply this article to
      your practice. Reflect on and write a short account of: 1. How you think this
      article will change your practice when assisting patients with sit-stand
      transfers. 2. How you could use this resource to educate your colleagues about
      sit-stand transfers.

PMID- 28488509
TI  - Children's nursing film.
AB  - A new short film celebrates the unique role of children's nurses, in response to
      concern about moves to sideline the specialty.

PMID- 28488508
TI  - Use and relevance of bibliometrics for nursing.
AB  - A vast and increasing scientific literature is published each year, including
      books, journals, research articles and reviews. One approach to determining the
      value of an academic publication involves measuring how often other academic
      writers or researchers refer to or cite it. This is the essence of bibliometrics.
      This article examines how bibliometrics has developed. It describes how analysing
      citations provides a measure of the influence of specific articles (individual
      article citations), to compare different journals (journal impact factor) and to
      examine the output and impact of individual academics (the h-index). Particular
      reference is made to nursing. Using citations should not be the only way that the
      value of scholarly work is judged, because there are limitations in using this
      method. However, bibliometrics provides an important, feasible and systematic
      means of reaching judgments about the importance of published works. As a result,
      it can be useful for examining the productivity and influence of individuals and
      institutions and for comparing different disciplines and journals.

PMID- 28488510
TI  - Keep staff safe and well.
AB  - When Denise McLaughlin read about a nurse who crashed her car following a 12-hour
      night shift with no break, she was inspired to act.

PMID- 28488512
TI  - Taking magnesium could prevent bone fractures in middle age.
AB  - Magnesium could prevent bone fractures as a leading cause of disability and ill
      health among middle-aged to older people, research suggests.

PMID- 28488511
TI  - Emergency care and NHS pay on RCN's congress agenda.
AB  - The NHS pay cap, the nursing associate role and the crisis in emergency medicine
      are among topics for debate at RCN congress.

PMID- 28488513
TI  - High or low birth weight may increase risk of liver disease.
AB  - Children with a high or low birth weight may be at an increased risk of
      developing non-alcoholic fatty liver disease (NAFLD), according to researchers.

PMID- 28488514
TI  - What is said by the bed?
AB  - We have been doing bedside nurse handovers for years (news online, 2 May) and
      it's absolutely what everyone should be doing. How anyone can hand a patient over
      to the next shift without actually being in front of them is beyond me.

PMID- 28488515
TI  - Sharing their stories helps young people to feel more understood.
AB  - My passion for improving mental health services started after a young woman I
      knew took her own life. She was part of a theatre group I volunteered for, and
      the distress experienced by fellow members prompted me to take action.

PMID- 28488516
TI  - Nursing shortages put future of NHS at risk.
AB  - When it comes to the future of the health service, pressure on the workforce is
      as great a threat, if not greater, than pressure on finances. This was my
      argument in evidence to the House of Lords' recent inquiry into the long-term
      sustainability of the NHS.

PMID- 28488517
TI  - Last chance for nursing course with bursary.
AB  - Would-be nurses have a last chance to train on a fully funded course before
      bursaries are scrapped in England - if they are ready to start at the end of
      June.

PMID- 28488518
TI  - Developing, implementing and evaluating a model for an outpatient self-harm
      service.
AB  - Aim To reduce the incidence of self-harming behaviour and improve well-being and
      experience of care for individuals who present regularly to the emergency
      department in one hospital following self-harm, by providing outpatient care.
      Method This was a 12-month nurse-led practice development project to develop,
      implement and evaluate a brief-intervention outpatient service for individuals
      who presented to the emergency department following self-harm and who were
      identified as being at risk of further self-harm. The service improvement was
      informed by an action research process and the principles of appreciative
      inquiry. Findings The project provided a short-term outpatient follow-up service,
      known as Brief Interventions in Repeat Self Harm (BIRSH), to patients who
      presented to the emergency department following self-harm, and who were
      considered at risk of further self-harm. The intervention enabled the clinician
      to validate the patient's distress and offer them short-term outpatient follow-up
      care. The BIRSH sessions were offered to 38 patients. A total of 26 patients
      attended one or more BIRSH session, and all of these individuals showed a
      reduction in the number of presentations to the emergency department following
      self-harm in the six months following the intervention, compared to the six
      months before the intervention. Conclusion The BIRSH outpatient service appears
      to have been a contributory factor in reducing self-harm for patients who engaged
      with the service. The service improvement was informed by an action research
      process and the principles of appreciative inquiry, which provided a positive,
      focused approach to the practice development project.

PMID- 28488519
TI  - Lessons from Denmark.
AB  - As part of a recent trip to Denmark, I visited Kolding Sygehus Hospital, where my
      friend is the head of midwifery.

PMID- 28488521
TI  - Cycling to work lowers risk of premature death by 41.
AB  - New study results suggest cycling to work is associated with a 45% lower risk of
      developing cancer and a 46% lower risk of heart disease, compared with a non
      active commute.

PMID- 28488520
TI  - Report predicts 12% drop in nurse numbers by 2020.
AB  - England could see a shortfall of 42,000 nurses by 2020, equivalent to 12% of the
      workforce, according to a new report.

PMID- 28488522
TI  - Helpline for people at end of life should be available across the UK, says nurse.
AB  - A nurse whose husband died at home is calling for the end of life helpline she
      staffs to be rolled out nationally.

PMID- 28488525
TI  - 'Nurse of the year is a champion for patients with learning disabilities'.
AB  - In 2009, neglect at a hospital in Wales contributed to the death of our brother
      Paul Ridd, who had severe learning disabilities. The ombudsman said the care he
      received had been 'dire'.

PMID- 28488524
TI  - Should I stay... or should I go?
AB  - If you want to move into a new role, you need to be able to sell yourself to
      prospective employers, and the first step is knowing what you are capable of.

PMID- 28488526
TI  - Preliminary evaluation for Bit1 as a potential biomarker for squamous cell
      carcinoma and adenocarcinoma of esophagus.
AB  - Mounting evidence has demonstrated that Bit1 has been investigated as an
      etiological factor for certain cancers, including esophageal squamous cell
      carcinoma reported in our previous study, but data regarding possible roles of
      Bit1 in esophageal squamous cell carcinoma and esophageal adenocarcinoma remain
      to be elucidated. The purpose of this study was to examine whether Bit1 can be a
      novel diagnostic marker for the patients with esophageal squamous cell carcinoma
      and esophageal adenocarcinoma. The results revealed that Bit1 level in esophageal
      squamous cell carcinoma was significantly higher than that in esophageal
      adenocarcinoma tissues ( p < 0.05); notably, Bit1 level in esophageal
      adenocarcinoma tissues was lower than that in paired normal tissues but no
      difference was found ( p > 0.05). Bit1 expression patterns were completely in
      accordance with matrix metalloproteinase 2 and Bcl-2 in esophageal squamous cell
      carcinoma and esophageal adenocarcinoma. In addition, Bit1, Bcl-2, and matrix
      metalloproteinase 2 expression patterns in different differentiated esophageal
      squamous cell carcinoma were higher than those in corresponding normal esophageal
      tissues. Bit1 expression in poorly differentiated esophageal squamous cell
      carcinoma was significantly higher than that in normal esophageal tissues ( p <
      0.05) but not in moderately and well-differentiated esophageal squamous cell
      carcinoma. Matrix metalloproteinase 2 expression patterns in poorly and
      moderately differentiated esophageal squamous cell carcinoma were significantly
      higher than those in corresponding normal esophageal tissues ( p < 0.01) but not
      in well-differentiated esophageal squamous cell carcinoma tissue ( p > 0.05). Bcl
      2 expression patterns in various differentiated esophageal squamous cell
      carcinoma were higher than those in corresponding normal esophageal tissues with
      no statistical differences ( p > 0.05). Importantly, Bit1 expression was
      positively correlated with both matrix metalloproteinase 2 and Bcl-2 expression
      in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues ( p <
      0.05). Collectively, these preliminary data support further investigation of Bit1
      as an important diagnostic factor for esophageal squamous cell carcinoma and
      esophageal adenocarcinoma.

PMID- 28488527
TI  - Clinical value of miR-452-5p expression in lung adenocarcinoma: A retrospective
      quantitative real-time polymerase chain reaction study and verification based on
      The Cancer Genome Atlas and Gene Expression Omnibus databases.
AB  - The role and mechanism of miR-452-5p in lung adenocarcinoma remain unclear. In
      this study, we performed a systematic study to investigate the clinical value of
      miR-452-5p expression in lung adenocarcinoma. The expression of miR-452-5p in 101
      lung adenocarcinoma patients was detected by quantitative real-time polymerase
      chain reaction. The Cancer Genome Atlas and Gene Expression Omnibus databases
      were joined to verify the expression level of miR-452-5p in lung adenocarcinoma.
      Via several online prediction databases and bioinformatics software, pathway and
      network analyses of miR-452-5p target genes were performed to explore its
      prospective molecular mechanism. The expression of miR-452-5p in lung
      adenocarcinoma in house was significantly lower than that in adjacent tissues (p
      < 0.001). Additionally, the expression level of miR-452-5p was negatively
      correlated with several clinicopathological parameters including the tumor size
      (p = 0.014), lymph node metastasis (p = 0.032), and tumor-node-metastasis stage
      (p = 0.036). Data from The Cancer Genome Atlas also confirmed the low expression
      of miR-452 in lung adenocarcinoma (p < 0.001). Furthermore, reduced expression of
      miR-452-5p in lung adenocarcinoma (standard mean deviations = -0.393, 95%
      confidence interval: -0.774 to -0.011, p = 0.044) was validated by a meta
      analysis. Five hub genes targeted by miR-452-5p, including SMAD family member 4,
      SMAD family member 2, cyclin-dependent kinase inhibitor 1B, tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, and tyrosine
      3-monooxygenase/tryptophan 5-monooxygenase activation protein beta, were
      significantly enriched in the cell-cycle pathway. In conclusion, low expression
      of miR-452-5p tends to play an essential role in lung adenocarcinoma.
      Bioinformatics analysis might be beneficial to reveal the potential mechanism of
      miR-452-5p in lung adenocarcinoma.

PMID- 28488528
TI  - Future perspectives of circulating tumor DNA in colorectal cancer.
AB  - Tumor biopsy is currently the gold standard for diagnosis and in determining cell
      signaling pathways involved in the development of treatment resistance. However,
      there are major challenges with this technique, including the need for serial
      sampling to monitor treatment resistance, which is invasive and also has the
      potential for selection bias due to intra-tumoral and inter-tumoral
      heterogeneity. These challenges highlight the need for more effective methods for
      obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells
      shed into the blood from the primary tumor and metastatic sites and consequently
      provides a comprehensive, real-time picture of the tumor burden in an individual
      patient. Indeed, liquid biopsy has the potential to revolutionize cancer
      management. Here, we review recent studies on the potential clinical applications
      of liquid biopsy using circulating tumor DNA in colorectal cancer, including
      screening, diagnosis, detection of minimal residual disease after surgery,
      detection of recurrence, prognosis, predicting treatment response, monitoring
      tumor burden or response during treatment, and tracking resistance. We also
      discuss recent data demonstrating the utility of detecting KRAS-mutated
      circulating tumor DNA, both at diagnosis to determine an appropriate treatment
      strategy and during anti-epidermal growth factor receptor therapy to predict
      treatment resistance. The future integration of liquid biopsy into clinical
      practice is discussed, together with alternative approaches and key questions
      that need to be answered in future clinical studies before this technology can be
      implemented and used routinely.

PMID- 28488529
TI  - ?

PMID- 28488530
TI  - ?

PMID- 28488531
TI  - ?

PMID- 28488532
TI  - ?

PMID- 28488533
TI  - ?

PMID- 28488534
TI  - ?

PMID- 28488535
TI  - ?

PMID- 28488536
TI  - ?

PMID- 28488537
TI  - ?

PMID- 28488538
TI  - ?

PMID- 28488539
TI  - ?

PMID- 28488540
TI  - ?

PMID- 28488541
TI  - MicroRNA-124 suppresses proliferation and glycolysis in non-small cell lung
      cancer cells by targeting AKT-GLUT1/HKII.
AB  - Non-small cell lung cancer accounts for 85% of all types of lung cancer and is
      the leading cause of worldwide cancer-associated mortalities. MiR-124 is
      epigenetically silenced in various types of cancer and plays important roles in
      tumor development and progression. MiR-124 was also significantly downregulated
      in non-small cell lung cancer patients. Glycolysis has been considered as a
      feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key
      enzymes in the regulation of glycolysis and energy metabolism in cancer cells.
      However, the role of miR-124 in non-small cell lung cancer cell proliferation,
      glycolysis, and energy metabolism remains unknown. In this research, cell
      proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid
      production were assessed; adenosine triphosphate content and NAD+/NADH were also
      detected. These tests were conducted using the normal non-small cell lung cancer
      cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics,
      miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we
      show that miR-124 overexpression directly decreased cell growth, glucose
      consumption, lactate production, and energy metabolism. MiR-124 also negatively
      regulates glycolysis rate-limiting enzymes, glucose transporter 1 and hexokinase
      II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but
      no regulatory effect on hypoxia-inducible factor 1-alpha/beta. Overexpression of
      AKT reverses the inhibitory effect of miR-124 on cell proliferation and
      glycolytic metabolism in non-small cell lung cancer. AKT inhibition blocks miR
      124 silencing-induced AKT1/2, glucose transporter 1, hexokinase II activation,
      cell proliferation, and glycolytic or energy metabolism changes. In summary, this
      study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and
      energy metabolism, potentially by targeting AKT1/2-glucose transporter
      1/hexokinase II in non-small cell lung cancer cells.

PMID- 28488542
TI  - CXCL11 mediates TWIST1-induced angiogenesis in epithelial ovarian cancer.
AB  - To investigate the role of TWIST1 in tumor angiogenesis in epithelial ovarian
      cancer and to identify key molecules involved in angiogenesis. TWIST1 small
      interfering RNA was transfected into A2780 cells, while a complementary DNA
      vector was transfected into non-malignant human ovarian surface epithelial cells
      to generate a TWIST1-overexpressing cell line. To evaluate how this affects
      angiogenesis, human umbilical vein endothelial cell tube formation assays were
      performed using the control and transfected cell lines. An antibody-based
      cytokine array was used to identify the molecules involved in TWIST1-mediated
      angiogenesis. After knockdown of TWIST1 via transfection of TWIST1 small
      interfering RNA into A2780 cells, the number of tubes formed by human umbilical
      vein endothelial cells significantly decreased in a tube formation assay. In a
      cytokine array, TWIST1 downregulation did not significantly decrease the
      secretion of the common pro-angiogenic factor, vascular endothelial growth
      factor, but instead inhibited the expression of the CXC chemokine ligand 11,
      which was confirmed by both an enzyme-linked immunosorbent assay and western
      blotting. In contrast, TWIST1 overexpression resulted in increased secretion of
      CXC chemokine ligand 11. Conversely, CXC chemokine ligand 11 downregulation did
      not inhibit the expression of TWIST1. Furthermore, the ability of TWIST1
      expressing A2780 cells to induce angiogenesis was found to be inhibited after CXC
      chemokine ligand 11 knockdown in a tube formation assay. TWIST1 plays an
      important role in angiogenesis in epithelial ovarian cancer and is mediated by a
      novel pro-angiogenic factor, CXC chemokine ligand 11. Downregulation of CXC
      chemokine ligand 11 can inhibit tumor angiogenesis, suggesting that anti-CXC
      chemokine ligand 11 therapy may offer an alternative treatment strategy for
      TWIST1-positive ovarian cancer.

PMID- 28488543
TI  - The transcription factor FOXA1 induces epithelial ovarian cancer tumorigenesis
      and progression.
AB  - FOXA1 (forkhead box A1), a member of the FOXA transcription factor superfamily,
      plays an important role in tumor occurrence and development. However, the
      relationship between FOXA1 and ovarian cancer has not been reported. We examined
      normal ovarian tissue and ovarian cancer tissue and found increased FOXA1
      expression in the cancer tissue. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and flow cytometry assays demonstrated that
      transfection with small interfering RNA to silence FOXA1 (si-FOXA1) in ovarian
      cancer cell lines decreased cell proliferation and induced apoptosis and S-phase
      arrest. In addition, si-FOXA1 transfection inhibited cell migration and invasion.
      Western blotting showed that si-FOXA1 transfection decreased the levels of YY1
      associated protein 1, cyclin-dependent kinase 1, cyclin D1, phosphatidylinositol
      3 kinase, E2F transcription factor 1, B-cell lymphoma 2, and vascular endothelial
      growth factor A protein. Based on these results, we suggest that FOXA1 plays a
      catalytic role in ovarian cancer pathogenesis and development by affecting the
      expression of the above-mentioned proteins.

PMID- 28488544
TI  - A long non-coding RNA lncRNA-PE promotes invasion and epithelial-mesenchymal
      transition in hepatocellular carcinoma through the miR-200a/b-ZEB1 pathway.
AB  - Long non-coding RNAs have been revealed to play important roles in the
      progression of hepatocellular carcinoma. However, the detailed mechanisms
      underlying their activities are not fully understood. Using microarray
      technology, a number of long non-coding RNAs were previously identified to be
      aberrantly expressed in hepatocellular carcinoma. In this study, one of these
      long non-coding RNAs, designated lncRNA-PE (lncRNA promotes epithelial
      mesenchymal transition), was further explored to study its expression profile and
      function. A cohort of human hepatocellular carcinoma tissue samples combined with
      benign controls and established human hepatocellular carcinoma cell lines were
      examined for the expression of lncRNA-PE. The biological functions of lncRNA-PE
      were examined by wound-healing and Transwell assays, which revealed that lncRNA
      PE promotes cell invasion and migration. By detecting the level of epithelial
      mesenchymal transition markers, lncRNA-PE was revealed to promote epithelial
      mesenchymal transition in hepatocellular carcinoma cells. Further study suggested
      that lncRNA-PE downregulated miR-200a/b by repressing the primary transcript
      expression, enhanced ZEB1 expression, and promoted epithelial-mesenchymal
      transition of hepatocellular carcinoma cells. All these data imply that lncRNA-PE
      might play an important role in hepatocellular carcinoma development via the miR
      200a/b-ZEB1 pathway.

PMID- 28488545
TI  - Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation
      status in codon 600 in borderline and low-grade ovarian cancers.
AB  - Epithelial ovarian tumors are a group of morphologically and genetically
      heterogeneous neoplasms. Based on differences in clinical phenotype and genetic
      background, ovarian neoplasms are classified as low-grade and high-grade tumor.
      Borderline ovarian tumors represent approximately 10%-20% of all epithelial
      ovarian masses. Various histological subtypes of ovarian malignancies differ in
      terms of their risk factor profiles, precursor lesions, clinical course, patterns
      of spread, molecular genetics, response to conventional chemotherapy, and
      prognosis. The most frequent genetic aberrations found in low-grade serous
      ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers,
      are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is
      substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The
      primary aim of this study was to determine whether fully integrated, real-time
      polymerase chain reaction-based IdyllaTM system may be useful in determination of
      BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors
      and low-grade ovarian carcinomas. The study included tissue specimens from 42
      patients with histopathologically verified ovarian masses, who were operated on
      at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University
      Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination
      of surgical specimens, 35 lesions were classified as low-grade ovarian
      carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF
      V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene,
      using an automated molecular diagnostics platform IdyllaTM. Cytoplasmic
      immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous
      superficial papilloma, serous papillary cystadenoma of borderline malignancy, and
      partially proliferative serous cystadenoma. All specimens with the expression of
      BRAF V600E (VE1) protein were tested positively for BRAF V600E/E2/D mutation. No
      statistically significant relationship (p > 0.05) was found between the presence
      of BRAF V600E mutation and the probability of 5-year survival. BRAF mutation
      testing with a rapid, fully integrated molecular diagnostics system IdyllaTM may
      be also a powerful prognostic tool in subjects with newly diagnosed serous
      borderline tumors, identifying a subset of patients who are unlikely to progress.

PMID- 28488546
TI  - Long non-coding RNA UCA1 can predict tumor lymph node metastasis.
AB  - Numerous studies suggested that long non-coding RNA UCA1 was highly expressed and
      played critical roles in the development and progression of various cancerous
      tissues and cells. However, little is known about the association between UCA1
      and tumor lymph node metastasis. In our study, a systematic review was conducted
      to evaluate the association between UCA1 expression and tumor lymph node
      metastasis and explore whether UCA1 can be a potential molecular marker for
      predicting the multiple tumor lymph node metastasis. The meta-analysis result
      showed that the number of lymph node metastasis in different tumorous types of
      UCA1 high-expression group was significantly higher compared with UCA1 low
      expression group (pooled odds ratio = 2.13, 95% confidence interval: 1.60-2.84, p
      < 0.05). To verify whether the above result was still valid in specific tumor
      type, we conducted a meta-analysis including four articles on colorectal cancer
      (pooled odds ratio = 2.07, 95% confidence interval: 1.28-3.34, p < 0.05). Based
      on the existing results, it can be explained that the long non-coding RNA UCA1
      was significantly associated with lymph node metastasis and both the results
      revealed that compared with UCA1 low-expression group, the lymph node metastasis
      rate of UCA1 high-expression group was statistically significantly elevated.
      Therefore, long non-coding RNA UCA1 has the potential of being a biological
      marker for predicting lymph node metastasis.

PMID- 28488547
TI  - Stimulatory role of interleukin 10 in CD8+ T cells through STATs in gastric
      cancer.
AB  - CD8+ T cells are considered to be critical in tumor surveillance and elimination.
      Increased CD8+ T cell frequency and function is associated with better prognosis
      in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8+
      T cell-mediated anti-tumor immunity. We therefore examined the interleukin 10
      expression and consumption in CD8+ T cells harvested from the peripheral blood
      and resected tumors of gastric cancer patients of stages II-IV. We found that the
      gastric cancer patients presented significantly elevated frequencies of
      interleukin 10-expressing cells in both CD4+ and CD8+ T cells compared to healthy
      controls. But distinctive from the interleukin 10-expressing CD4+ T cells, which
      increased in frequency in advanced cancer, the interleukin 10-expressing CD8+ T
      cells did not increase with cancer stage in the peripheral blood and actually
      decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10
      receptor expression was also enriched in interferon gamma-expressing activated
      CD8+ T cells. Compared to interleukin 10-nonexpressing CD8+ T cells, interleukin
      10 receptor-expressing CD8+ T cells secreted significantly elevated interferon
      gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8+ T cells with
      interleukin 10 alone could significantly enhance CD8+ T cell survival, an effect
      dependent on interleukin 10 receptor expression. Interleukin 10 also increased
      CD8+ T cell proliferation synergistically with interferon gamma but not alone.
      Analysis of downstream signal transducer and activator of transcription molecules
      showed that interleukin 10 treatment significantly increased the phosphorylation
      of signal transducer and activator of transcription 3 and signal transducer and
      activator of transcription 1 to lesser extent. Together, these results
      demonstrate that interleukin 10 possessed stimulatory roles in activated CD8+ T
      cells from gastric cancer patients.

PMID- 28488548
TI  - Angiotensinogen (AGT) gene missense polymorphisms (rs699 and rs4762) and diabetic
      nephropathy in Caucasians with type 2 diabetes mellitus.
AB  - Gene polymorphisms associated with the renin-angiotensin-aldosterone system
      (RAAS) have been extensively studied in diabetic nephropathy (DN) patients, due
      to therapeutic potential of targeting the RAAS and slowing down the disease
      progression. The aim of our study was to examine the association between
      angiotensinogen (AGT) gene polymorphisms (rs699 and rs4762) and DN in Caucasians
      with type 2 diabetes mellitus (T2DM). A total of 651 unrelated Slovenian
      (Caucasian) T2DM patients were tested for AGT rs699 and rs4762 polymorphisms
      using a novel fluorescence-based kompetitive allele-specific polymerase chain
      reaction (KASPar) assay. A study group consisted of 276 T2DM patients with DN,
      while control group included 375 patients without DN but who have had T2DM for
      >10 years. For rs699 polymorphism, the frequencies of GG, GA and AA genotypes
      were 20.6%, 52.2% and 27.2%, respectively in T2DM patients and 23.4%, 48.1% and
      28.5%, respectively in controls. The distributions of GG, GA and AA genotypes for
      rs4762 polymorphism were 73.9%, 23.2% and 2.9%, respectively in T2DM patients and
      70.4%, 27.5% and 2.1%, respectively in controls. No significant differences in
      the allele frequencies were found between T2DM patients and controls for both
      polymorphisms. AGT rs699 and rs4762 missense polymorphisms are not associated
      with DN in our subset of Slovenian T2DM patients.

PMID- 28488549
TI  - Prevalence of F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms in Bosnian
      women with pregnancy loss.
AB  - The relationship between genetic risk factors of thrombophilia and pregnancy loss
      (PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR
      677C>T polymorphisms that may predispose women to microthrombosis during the
      stages of embryo implantation and placentation. Although, the frequencies of
      these polymorphisms were reported in different populations, such studies have not
      yet been performed in Bosnian population. In this study, we determined the
      prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133)
      polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (+/
      5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age
      31.4 (+/-6.7) years] with at least one live-born child were included. We used
      real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A
      and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for
      analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was
      significantly higher in women with venous thrombosis (VT) compared to women
      without VT (p = 0.047 and p = 0.001, respectively). There was no significant
      difference in the distribution of MTHFR genotypes and alleles between these two
      groups. In addition, we observed no significant differences in the genotype and
      allele frequencies between the group with PL and control group, for all
      investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2),
      and 677T (MTHFR) reported in this study are consistent with the data obtained for
      other European countries, however, we were not able to confirm the association
      between the three polymorphisms and PL in Bosnian women.

PMID- 28488550
TI  - Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia.
AB  - Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced
      expression of microRNA-192 (miR-192) has been detected in many cancers. In this
      study, we investigated the role of miR-192 in cell proliferation and cell cycle
      control in NALM-6 cell line, a model of acute lymphoblastic leukemia (ALL). Cell
      cycle analysis by DNA content using propidium iodide staining and cell apoptosis
      analysis using Annexin V assay were carried out. Cell proliferation changes were
      monitored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. In addition, the relative changes in P53, BAX, CASP3, and BCL-2 gene
      expression were determined by quantitative reverse transcription PCR.
      Overexpression of miR-192 resulted in cell proliferation arrest in ALL cells.
      After 72 and 96 hours of transduction, apoptosis was significantly increased in
      the cells transduced with miR-192-overexpressing virus compared with control
      cells. The expression of P53, BAX, and CASP3 increased after 48 hours of
      transduction in miR-192-overexpressing cells, but no change was observed in BCL-2
      expression. The G0/S and G1/S ratio changed to 7.5 and 4.5, respectively, in the
      cells overexpressing miR-192 compared with controls. The results of our study
      suggest, for the first time, tumor suppressive effects of miR-192 in ALL cells.

PMID- 28488551
TI  - [Emergency laparotomy in a trauma patient].
AB  - - Emergency laparotomy in trauma patients can be part of the resuscitation
      process, is based on damage control principles and is therefore fundamentally
      different from elective laparotomy, for example in case of malignancies. -
      Indications for emergency laparotomy after trauma are based on haemodynamic
      instability of the patient and the procedure is focused on restoring the
      patient's physiological condition.- Haemodynamic and biochemical parameters are
      used to determine the rest of the strategy. In order to optimize the procedure,
      the entire treatment team should be practiced in this.- Fewer and fewer surgeons
      are carrying out general laparotomies and even fewer are carrying out emergency
      laparotomies after trauma.- Knowledge and skills about emergency laparotomy after
      trauma are at risk of disappearing because of this, not only for surgeons but
      also for other team members.- Increased centralisation, team training, more
      cooperation and consultation for specific indications may all contribute to
      expertise preservation.

PMID- 28488552
TI  - [Should every doctor be allowed to use ultrasound? Dilemmas surrounding broad
      application of ultrasound in clinical practice].
AB  - Ultrasound is rapidly gaining ground in clinical medicine. This offers distinct
      advantages for diagnosis and treatment. This is notably the case when moving
      images are created by the treating physician, who can integrate them immediately
      with all other clinical information. The downside of a broad application of
      ultrasound is an increase in the number of incidental findings and missed
      diagnoses. This is amplified by the frequent lack of formal requirements for
      training and skills. Storage of ultrasound images may furthermore lead to
      verifiable misinterpretations. We are of the opinion that responsible integration
      of ultrasound in clinical practice requires clear peer agreements without
      sectarian thinking. To illustrate this, we discuss the dilemmas surrounding
      increased use of ultrasound from a medicolegal perspective.

PMID- 28488553
TI  - [Is dementia preventable through intensive vascular care? The preDIVA trial].
AB  - OBJECTIVE: To assess whether intensive vascular care in GP practices can prevent
      dementia in a population of community-dwelling older people. METHOD: This
      pragmatic cluster-randomised open-label study (ISRCTN29711771) was conducted in
      persons aged 70-78 years who were registered with Dutch GP practices. The only
      exclusion criteria were a diagnosis of dementia and limited life expectancy.
      Practices were randomly assigned to an intervention arm or a control arm.
      Participants in the interventional arm underwent a cardiovascular check-up every
      4 months for six years by a practice nurse. Primary outcomes were cumulative
      incidence of dementia and functional limitations. Main secondary outcomes were
      the incidence of cardiovascular disease and mortality. RESULTS: Between June 2006
      and March 2009, 116 GP practices (3526 participants) were recruited and randomly
      assigned: 63 (1890 participants) to the intervention group and 53 (1636
      participants) to the control group. Primary outcome data were obtained for 3454
      (98%) participants; median follow-up was 6.7 years. In this period, dementia was
      diagnosed in 121/1853 (6.5%) participants in the intervention group and in
      112/1601 (7.0%) participants in the control group. This difference was not
      significant (hazard ratio 0.92, 95% CI 0.71-1.19). No differences were found with
      regard to functional decline, incident cardiovascular disease and mortality.
      CONCLUSION: Long-term intensive vascular care for community-dwelling elderly
      patients, provided in a primary care setting, does not result in a reduced
      incidence of dementia, functional limitations or mortality. There is, however,
      possibly an effect in elderly patients with untreated or sub-optimally treated
      hypertension; this warrants further research.

PMID- 28488554
TI  - [How can life-threatening external blood loss be stopped? Treatment options in
      the prehospital phase].
AB  - - 3,500 people die of injuries in the Netherlands every year; 40% of the deaths
      are attributable to bleeding.- Treatment of patients with life-threatening blood
      loss is part of the trauma care continuum: all the way from incident to hospital
      treatment.- This article presents an overview of all treatment options for
      stopping life-threatening external blood loss, divided in medical assistance
      phases. It also makes a distinction between different types of care providers,
      based on the presence or absence of their medical skills.

PMID- 28488555
TI  - [Syncope; suspect pulmonary embolism, especially in the elderly].
AB  - Syncope can be caused by a pulmonary embolism. This applies in particular to
      elderly patients admitted with syncope; in the general population, however,
      syncope is far more frequently caused by a vasovagal response or orthostatic
      hypotension. Syncope can be the symptom of a pulmonary embolism, even in the
      absence of any clinical manifestations of this diagnosis; it is, therefore,
      important to exclude pulmonary embolism in any syncope patient in the accident
      and emergency department by applying the Wells clinical decision rule. GPs should
      also be alert to syncope as a possible symptom of pulmonary embolism, and be
      alert to breathing rate and signs of venous thrombosis.

PMID- 28488556
TI  - [Treating physicians can perform simple ultrasounds; triage ultrasonography
      should be reserved for radiologists].
AB  - We feel that, in trained hands, point-of-care ultrasonography by non-radiologists
      is of value to patient care. However, more extensive ultrasonography, i.e.,
      triage ultrasonography, requires a skill set and a clinical environment that can
      currently only be provided by radiologists.

PMID- 28488557
TI  - [Added value of observational studies in surgery: the hierarchical structure of
      study designs requires a more refined approach].
AB  - The randomised placebo-controlled trial (RCT) is the gold standard for the
      evaluation of medical interventions. Observational studies, on the other hand,
      usually do not get much credit. For studies investigating surgical interventions
      this does not always seem entirely justified. A more refined approach might be
      needed for the often-used hierarchical structure of research designs. Instead of
      a strict separation of results from RCTs and other designs, results of the
      different designs should rather be regarded as complementary to each other when
      evaluating surgical interventions in traumatology.

PMID- 28488558
TI  - [Identifying mild traumatic brain injury: clinical signs and consequences].
AB  - Identification of patients with mild traumatic brain injury (TBI) is important
      since 85,000 patients visit the emergency department with a head trauma annually.
      Although most patients recover well, 15-20% of the patients with head trauma
      develop persistent symptoms that interfere with resumption of daily activities.
      It is particularly important to identify the clinical signs that define mild TBI.
      Presence of anterograde amnesia after the injury, for example, is an important
      clinical diagnostic sign to establish the diagnosis of TBI. Posttraumatic
      emotional distress may increase posttraumatic symptoms. General practitioners
      should be aware of the problems in this patient group and identify patients with
      mild TBI who are at risk of developing persistent symptoms that limit
      participation in society.

PMID- 28488559
TI  - [Hip fracture in elderly patients; additional value of a multidisciplinary
      approach and concentration of care].
AB  - Management of elderly patients with a proximal femoral fracture is an increasing
      challenge for the Dutch healthcare system. Proximal femoral fractures in the
      elderly have high morbidity and mortality rates. Furthermore, healthcare costs
      for this group of patients are rising. Referral, operation and postoperative care
      demand efficient collaboration between healthcare professionals. Every step in
      this chain of events is crucial for optimal treatment results. Multidisciplinary
      orthogeriatric trauma care shows promising results. In addition, high volume care
      results in better outcome of geriatric trauma patients.

PMID- 28488560
TI  - [The effects of severe and very severe injuries].
AB  - - The effects of severe injuries can be charted using the International
      Classification of Functioning, Disability and Health (ICF) model and the burden
      of disease model, in which the burden of disease is expressed in 'disability
      adjusted life years' (DALYs). - Severe accidents cause 10 DALYs per 1000 people,
      which is comparable with the burden of disease of mood disorders and lung cancer.
      In the Netherlands, severe injury victims are often males aged < 40 years, who
      are often injured in road traffic accidents. - The average hospital stay after a
      severe injury is one month, after which almost 75% of the patients are discharged
      home, while one quarter subsequently stay in rehabilitation facilities for 3-6
      months. More than half return to their original employment. - Patients with
      thoracic and abdominal injuries recover relatively well, whereas injuries of the
      lower extremities, brain and spinal cord give a relatively poor prognosis.
      Comorbidity increases the chance of a less good recovery. Older people who
      survive an accident recover relatively well.

PMID- 28488561
TI  - An Integrative Cognitive Model of Internalized Stigma in Psychosis.
AB  - BACKGROUND: Internalized stigma is a significant difficulty for those who
      experience psychosis, but it has never been conceptualized using cognitive
      theory. AIMS: The aim of this paper is to outline a cognitive model
      conceptualizing internalized stigma experienced by people who also experience
      psychosis. METHOD: Previous literature is reviewed, critiqued and synthesized to
      develop the model. It draws upon previous social cognitive models of internalized
      stigma and integrates cognitive behavioural theory and social mentality theory.
      RESULTS: This paper identifies key cognitive, behavioural and emotional processes
      that contribute to the development and maintenance of internalized stigma, whilst
      also recognizing the central importance of cultural context in creating negative
      stereotypes of psychosis. Moreover, therapeutic strategies to alleviate
      internalized stigma are identified. A case example is explored and a formulation
      and brief intervention plan was developed in order to illustrate the model in
      practice. CONCLUSION: An integrative cognitive model is presented, which can be
      used to develop individualized case formulations, which can guide cognitive
      behavioural interventions targeting internalized stigma in those who experience
      psychosis. More research is required to examine the efficacy of such
      interventions. In addition, it is imperative to continue to research
      interventions that create change in stigma at a societal level.

PMID- 28488562
TI  - Exploring the health status of older persons in Sub-Saharan Africa.
AB  - Sub-Saharan Africa (SSA) has traditionally had a low life expectancy due to the
      onslaught of the HIV epidemic, high levels of chronic diseases, injuries,
      conflict and undernutrition. Therefore, research into public health concerns of
      older persons has largely been overlooked. With a growing population, the roll
      out of antiretroviral treatment, and the effects of globalisation, SSA is
      experiencing an increase in the number of people over 50 years of age as well as
      an increase in the prevalence of non-communicable diseases (NCD). The aim of this
      review is to highlight available research on the health status of older persons
      in SSA, and to identify the current gaps that warrant further investigation. A
      literature search was conducted across multiple databases to identify studies in
      SSA on older persons (aged 50 years and older) related to health indicators
      including nutritional status, NCD and HIV burden. While it was concluded that
      older persons are at an increased risk of poor health, it was also determined
      that significant gaps exist in this particular area of research; namely nutrient
      deficiency prevalence. Resources should be directed towards identifying the
      health concerns of older persons and developing appropriate interventions.

PMID- 28488563
TI  - 3-D printing open-source click-MUAC bands for identification of malnutrition.

PMID- 28488566
TI  - Expanding the substrates for a bacterial hydrogenlyase reaction.
AB  - Escherichia coli produces enzymes dedicated to hydrogen metabolism under
      anaerobic conditions. In particular, a formate hydrogenlyase (FHL) enzyme is
      responsible for the majority of hydrogen gas produced under fermentative
      conditions. FHL comprises a formate dehydrogenase (encoded by fdhF) linked
      directly to [NiFe]-hydrogenase-3 (Hyd-3), and formate is the only natural
      substrate known for proton reduction by this hydrogenase. In this work, the
      possibility of engineering an alternative electron donor for hydrogen production
      has been explored. Rational design and genetic engineering led to the
      construction of a fusion between Thermotoga maritima ferredoxin (Fd) and Hyd-3.
      The Fd-Hyd-3 fusion was found to evolve hydrogen when co-produced with T.
      maritima pyruvate :: ferredoxin oxidoreductase (PFOR), which links pyruvate
      oxidation to the reduction of ferredoxin. Analysis of the key organic acids
      produced during fermentation suggested that the PFOR/Fd-Hyd-3 fusion system
      successfully diverted pyruvate onto a new pathway towards hydrogen production.

PMID- 28488568
TI  - Life Cycle Energy Analysis of Reclaimed Water Reuse Projects in Beijing.
AB  - To illustrate the benefits of water reuse project, the process-based life cycle
      analysis (LCA) could be combined with input-output LCA to evaluate the water
      reuse project. Energy is the only evaluation parameter used in this study. Life
      cycle assessment of all energy inputs (LCEA) is completed mainly by the life
      cycle inventory (LCI), taking into account the full life cycle including the
      construction, the operation, and the demolition phase of the project. Assessment
      of benefit from water reuse during the life cycle should focus on wastewater
      discharge reduction and water-saving benefits. The results of LCEA of Beijing
      water reuse project built in 2014 in a comprehensive way shows that the benefits
      obtained from the reclaimed water reuse far exceed the life cycle energy
      consumption. In this paper, the authors apply the LCEA model to estimate the
      benefits of reclaimed water reuse projects quantitatively.

PMID- 28488569
TI  - Gene Expression in the Liver Remnant Is Significantly Affected by the Size of
      Partial Hepatectomy: An Experimental Rat Study.
AB  - Extended hepatectomies may result in posthepatectomy liver failure, a condition
      with a high mortality. The main purpose of the present study was to investigate
      and compare the gene expression profiles in rats subjected to increasing size of
      partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90%
      PH, sham operation, or no operation. Twenty-four hours following resection, liver
      tissue was harvested and genome-wide expression analysis was performed. Cluster
      analysis revealed two main groupings, one containing the PH(90%) and one
      containing the remaining groups [baseline, sham, PH(30%), and PH(70%)].
      Categorization of specific affected molecular pathways in the PH(90%) group
      revealed a downregulation of cellular homeostatic function degradation and
      biosynthesis, whereas proliferation, cell growth, and cellular stress and injury
      were upregulated in the PH(90%) group. After PH(90%), the main upregulated
      pathways were mTOR and ILK. The main activated upstream regulators were
      hepatocyte growth factor and transforming growth factor. With decreasing size of
      the future liver remnant, the liver tended to prioritize expression of genes
      involved in cell proliferation and differentiation at the expense of genes
      involved in metabolism and body homeostasis. This prioritizing may be an
      essential molecular explanation for posthepatectomy liver failure.

PMID- 28488570
TI  - Synergy Effects of Hydrodynamic Conditions and Surfactant on Sorption Behavior of
      Bisphenol A.
AB  - The synergy effects of hydrodynamic conditions and cetyl trimethylammonium
      bromide (CTAB) on the distribution behavior of bisphenol A (BPA) in sediment have
      been investigated using particle entrainment simulator (PES) and water bath
      shaker. The results showed that when the concentration of CTAB is below its
      critical micelle concentration (CMC), the shear stress has almost no effect on
      the equilibrium sorption amount of BPA on sediment, which is mainly related to
      the surfactant concentration. The sorption rates in the rapid sorption phase
      increased with increasing CTAB content and shear stress. When the concentration
      of CTAB exceeded CMC, equilibrium sorption amount and corresponding time of BPA
      on sediment both decreased with increasing shear stress, mainly because the
      hydrodynamic conditions enhanced the solubilization ability of the surfactant on
      BPA. It was also found that the sorption rate constant showed a linear increase
      trend with increasing shear stress.

PMID- 28488571
TI  - Performance study of a low-cost adsorbent - raw date pits - for removal of azo
      dye in aqueous solution.
AB  - The feasibility of using natural waste (raw date pits) as a low-cost adsorbent
      for the adsorption of an anionic dye (Congo red) from aqueous solution has been
      investigated. Adsorption optimized conditions were obtained at low dose 1 g/L,
      initial dye concentration 100 mg/L, pH 2, equilibrium contact time 120 min, and
      temperature 20  degrees C. The corresponding adsorption capacity was around 70
      mg/g and could reach 150 mg/g by increasing the ionic strength of the dye
      solution (0.05 M CaCl2). These results are well modeled by Freundlich isotherm
      and kinetics study followed by pseudo second-order model. Thermodynamic
      parameters indicate that the adsorption process is endothermic and not
      spontaneous. The tests of desorption-regeneration showed that the studied
      adsorbent has the disadvantage of the loss of efficiency at its reuse but this is
      offset by its abundance. Based on these results, it can be used as competitive
      material for the removal of dyes.

PMID- 28488572
TI  - Acute hypocalcemia following kidney transplantation may depend on the type of
      remote parathyroidectomy: a retrospective cohort study?.
AB  - BACKGROUND: Secondary hyperparathyroidism is a common complication of chronic
      kidney disease. When medical management fails, parathyroidectomy (PTX) is a
      treatment option. The two most common types are subtotal PTX and total PTX with
      autotransplantation (AT). To date, there is no consensus as to which procedure is
      preferable, especially in patients who are candidates for future kidney
      transplantation. The aim of this study was to identify if the type of PTX is a
      risk factor for acute postrenal transplant (postRTX) hypocalcemia and a concern
      for problems with long-term calcium homeostasis. METHODS: Renal transplant
      recipients at Rhode Island Hospital from 2005 to 2014 were screened for prior
      PTX. Out of 297 participants, 11 patients met the criteria. They were further
      divided into subtotal PTX (n = 5) vs. total PTX+AT (n = 6). Immediate
      postoperative (14 days) and long-term (1 year) calcium levels were followed and
      analyzed. Linear growth models were used to determine the effects of type of
      parathyroidectomy (subtotal PTX, total PTX+AT) alone on hypocalcemia over time.
      In these models, pretransplant levels of calcium and PTH were included as
      covariates. RESULTS: Baseline characteristics showed that prerenal transplant
      (preRTX) parathyroid hormone (PTH) levels were lower in total PTX+AT vs. subtotal
      PTX (3.5 vs. 247.2 mg/dL, p < 0.005). PreRTX calcium levels were slightly lower
      in subtotal PTX (9.5 vs. 8.25 mg/dL, p < 0.01), but were within normal limits for
      both groups. No significant differences were noted between total vitamin D levels
      and time between PTX and RTX. Within 14 days postRTX, the total PTX+AT group had
      lower average calcium levels (5.8 vs 8.8 mg/dL, p < 0.001); however, both groups
      had normal and stable calcium levels from 1 month to 1 year after transplant.
      This was further supported after adjusting for preRTX levels of calcium and PTH,
      showing a significant interaction between treatment and time such that patients
      had lower calcium levels if they underwent total PTX+AT vs. subtotal PTX within
      14 days postRTX (beta = -0.204, SE = 0.039, p < 0.001) (<figtable-ref>Figure
      1</figtable-ref>) but not at 1 year postRTX (beta = 0.035, SE = 0.075, p =
      0.640). CONCLUSION: This study suggests that total PTX+AT increases the risk for
      acute postRTX hypocalcemia but has no effect on long-term calcium homeostasis. We
      speculate that the acuity of the hypocalcemia may be compounded by high-dose
      glucocorticoids required for induction, in addition to the preoperative
      undetectable PTH. Thus, prior to RTX, physicians should take into account the
      type of remote PTX. If a patient had a total PTX+AT, then postRTX hypocalcemia is
      likely to occur.?.

PMID- 28488584
TI  - Clinicopathologic significance and prognostic value of Ki-67 expression in
      patients with gastric cancer: a meta-analysis.
AB  - BACKGROUND: The prognostic value and clinicopathologic significance of Ki-67
      expression in gastric cancer patients was controversial. This meta-analysis was
      performed to clarify the prognostic value and clinicopathologic significance of
      Ki-67 expression in gastric cancer patients. MATERIALS AND METHODS: Several
      electronic databases were searched for eligible studies. The pooled odds ratio
      (OR), hazard ratios (HR) and 95% confidence interval(CI) were calculated to
      explore the prognostic value and clinicopathologic significance of Ki-67
      expression for disease free survival and overall survival. RESULTS: Totally 5600
      gastric cancer patients from 29 studies were included in this study. High Ki-67
      expression was significantly related with Lauren's classification (OR = 1.70; P =
      0.001; 95%CI: 1.40-2.06) and tumor size(OR = 1.54; P = 0.006; 95%CI: 1.14-2.09).
      However, high Ki-67 expression was not significantly associated with lymph node
      metastasis (OR = 1.37; P = 0.138; 95% CI: 0.90-2.08) , tumor stage (OR = 1.31; P
      = 0.296; 95% CI: 0.79-2.16) and tumor differentiation (OR = 1.03; P = 0.839; 95%
      CI: 0.78-1.35). The pooled HRs were 1.87(P = 0.001; 95% CI 1.30-2.69) for disease
      free survival and 1.23(P = 0.005; 95% CI 1.06-1.42) for overall survival.
      CONCLUSIONS: High Ki-67 expression may serve as a predictive biomarker for poor
      prognosis in gastric cancer patients. Stratification by Ki-67 expression may be a
      consideration for selection of therapeutic regimen and integrated managements.

PMID- 28488588
TI  - Leaf-inspired microcontact printing vascular patterns.
AB  - The vascularization of tissue grafts is critical for maintaining viability of the
      cells within a transplanted graft. A number of strategies are currently being
      investigated including very promising microfluidics systems. Here, we explored
      the potential for generating a vasculature-patterned endothelial cells that could
      be integrated into distinct layers between sheets of primary cells. Bioinspired
      from the leaf veins, we generated a reverse mold with a fractal vascular
      branching pattern that models the unique spatial arrangement over multiple length
      scales that precisely mimic branching vasculature. By coating the reverse mold
      with 50 MUg ml-1 of fibronectin and stamping enabled selective adhesion of the
      human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix,
      we show that a vascular-branching pattern can be transferred by microcontact
      printing. Moreover, this pattern can be maintained and transferred to a 3D
      hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be
      observed migrating and sprouting into Matrigel. These printed vascular branching
      patterns, especially after transfer to 3D hydrogels, provide a viable alternative
      strategy to the prevascularization of complex tissues.

PMID- 28488589
TI  - Quasicrystalline and crystalline types of local protein order in capsids of small
      viruses.
AB  - Like metal alloys and micellar systems in soft matter, the viral capsid
      structures can be of crystalline and quasicrystalline types. We reveal the local
      quasicrystalline order of proteins in small spherical viral capsids using their
      nets of dodecahedral type. We show that the structure of some of the viral shells
      is well described in terms of a chiral pentagonal tiling, whose nodes coincide
      with centers of mass of protein molecules. The chiral protein packing found in
      these capsids originates from the pentagonal Penrose tiling (PPT), due to a
      specific phason reconstruction needed to fit the protein order at the adjacent
      dodecahedron faces. Via examples of small spherical viral shells and geminate
      capsid of a Maize Streak virus, we discuss the benefits and shortcomings of the
      usage of a dodecahedral net in comparison to icosahedral one, which is commonly
      applied for the modeling of viral shells with a crystalline local order.

PMID- 28488590
TI  - Synaptic transistor with a reversible and analog conductance modulation using a
      Pt/HfOx/n-IGZO memcapacitor.
AB  - A synaptic transistor emulating the biological synaptic motion is demonstrated
      using the memcapacitance characteristics in a Pt/HfOx/n-indium-gallium-zinc-oxide
      (IGZO) memcapacitor. First, the metal-oxide-semiconductor (MOS) capacitor with
      Pt/HfOx/n-IGZO structure exhibits analog, polarity-dependent, and reversible
      memcapacitance in capacitance-voltage (C-V), capacitance-time (C-t), and voltage
      pulse measurements. When a positive voltage is applied repeatedly to the Pt
      electrode, the accumulation capacitance increases gradually and sequentially. The
      depletion capacitance also increases consequently. The capacitances are restored
      by repeatedly applying a negative voltage, confirming the reversible
      memcapacitance. The analog and reversible memcapacitance emulates the
      potentiation and depression synaptic motions. The synaptic thin-film transistor
      (TFT) with this memcapacitor also shows the synaptic motion with gradually
      increasing drain current by repeatedly applying the positive gate and drain
      voltages and reversibly decreasing one by applying the negative voltages,
      representing synaptic weight modulation. The reversible and analog conductance
      change in the transistor at both the voltage sweep and pulse operations is
      obtained through the memcapacitance and threshold voltage shift at the same time.
      These results demonstrate the synaptic transistor operations with a MOS
      memcapacitor gate stack consisting of Pt/HfOx/n-IGZO.

PMID- 28488591
TI  - Red-emission phosphor's brightness deterioration by x-ray and brightness recovery
      phenomenon by heating.
AB  - There are no feasible real-time and direct skin dosimeters for interventional
      radiology. One would be available if there were x-ray phosphors that had no
      brightness change caused by x-ray irradiation, but the emission of the Y2O3:Eu,
      (Y, Gd, Eu)BO3, and YVO4:Eu phosphors investigated in our previous study was
      reduced by x-ray irradiation. We found that the brightness of those phosphors
      recovered, and the purpose of this study is to investigate their recovery
      phenomena. It is expected that more kinds of phosphors could be used in x-ray
      dosimeters if the brightness changes caused by x-rays are elucidated and
      prevented. Three kinds of phosphors-Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu-were
      irradiated by x-rays (2 Gy) to reduce their brightness. After the irradiation,
      brightness changes occurring at room temperature and at 80  degrees C were
      investigated. The irradiation reduced the brightness of all the phosphors by 5%
      10%, but the brightness of each recovered immediately both at room temperature
      and at 80  degrees C. The recovery at 80  degrees C was faster than that at room
      temperature, and at both temperatures the recovered brightness remained at 95%
      98% of the brightness before the x-ray irradiation. The brightness recovery
      phenomena of Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu phosphors occurring after
      brightness deterioration due to x-ray irradiation were found to be more
      significant at 80  degrees C than at room temperature. More kinds of phosphors
      could be used in x-ray scintillation dosimeters if the reasons for the brightness
      changes caused by x-rays were elucidated.

PMID- 28488592
TI  - Reduction of interface traps between poly-Si and SiO2 layers through the
      dielectric recovery effect during delayed pulse bias stress.
AB  - We investigate the interface trap behavior between tunneling oxide and poly-Si
      channel layer post erase/write cycling with a delayed pulse by using deep level
      transient spectroscopy. For comparison of the defect states depending on the
      stress pulses, a Schottky and a metal-oxide semiconductor device were fabricated.
      A defect state at about E c -0.51 eV in the Schottky device was measured before
      the annealing process. Three-hole trap states with activation energies of E v
      +0.28 eV, E v +0.53 eV, and E v +0.76 eV appeared after the post-annealing
      process. The electron trap was about E c -0.15 eV after erase/write 3000 cycling
      was applied at +/-10 V for 100 ms at 25  degrees C and 85  degrees C. These
      defect states may have an effect on the charge loss behavior of the electrons
      localized in the charge trap layer at the retention mode of three-dimensional non
      volatile memory devices. Dramatically, after the endurance stress was applied
      with a delayed pulse of 300 cycling at 85  degrees C for 50.4 h, no interface
      traps of the deep level transient spectroscopy spectra appeared. Dielectric
      recovery can decrease the density of the interface trap and improve the retention
      properties. This may have been caused by the passivation effect on the dangling
      bond of the interface traps.

PMID- 28488593
TI  - Towards a new dose and dose-rate effectiveness factor (DDREF)? Some comments.
AB  - The aim of this article is to offer a broader, mechanism-based, analytical tool
      than that used by (Ruhm et al 2016 Ann. ICRP 45 262-79) for the interpretation of
      cancer induction relationships. The article explains the limitations of this
      broader analytical tool and the implications of its use in view of the
      publications by Leuraud et al 2015 (Lancet Haematol. 2 e276-81) and Richardson et
      al 2015 (Br. Med. J. 351 h5359). The publication by Ruhm et al 2016 (Ann. ICRP 45
      262-79), which is clearly work in progress, reviews the current status of the
      dose and dose-rate effectiveness factor (DDREF) as recommended by the ICRP. It
      also considers the issues which might influence a reassessment of both the value
      of the DDREF as well as its application in radiological protection. In this
      article, the problem is approached from a different perspective and starts by
      commenting on the limited scientific data used by Ruhm et al 2016 (Ann. ICRP 45
      262-79) to develop their analysis which ultimately leads them to use a linear
      quadratic dose effect relationship to fit solid cancer mortality data from the
      Japanese life span study of atomic bomb survivors. The approach taken here
      includes more data on the induction of DNA double strand breaks and, using
      experimental data taken from the literature, directly relates the breaks to cell
      killing, chromosomal aberrations and somatic mutations. The relationships are
      expanded to describe the induction of cancer as arising from radiation induced
      cytological damage coupled to cell killing since the cancer mutated cell has to
      survive to express its malignant nature. Equations are derived for the induction
      of cancer after both acute and chronic exposure to sparsely ionising radiation.
      The equations are fitted to the induction of cancer in mice to illustrate a dose
      effect relationship over the total dose range. The 'DDREF' derived from the two
      equations varies with dose and the DDREF concept is called into question.
      Although the equation for acute exposure can be used to analyse atomic bomb
      survivor data, the fitting is dominated by the quadratic dose component. Thus,
      little useful information can be derived about the linear dose component which is
      important for the derivation of low dose rate risk. The ICRP are advised to
      derive the risk at low dose rates from epidemiological studies of, for example,
      worker populations, together with information from cellular radiation biological
      research.

PMID- 28488594
TI  - Large scale production and controlled deposition of single HUVEC spheroids for
      bioprinting applications.
AB  - We present (1) a fast and automated method for large scale production of HUVEC
      spheroids based on the hanging drop method and (2) a novel method for well
      controlled lateral deposition of single spheroids by drop-on-demand printing.
      Large scale spheroid production is achieved via printing 1536 droplets of HUVEC
      cell suspension having a volume of 1 MUl each within 3 min at a pitch of 2.3 mm
      within an array of 48 * 32 droplets onto a flat substrate. Printing efficiencies
      between 97.9% and 100% and plating efficiencies between 87.3% and 100% were
      achieved. Harvested spheroids (consisting of approx. 250 HUVECs each) appear
      uniform in size and shape. After incubation and harvesting, the spheroids are
      deposited individually in user-defined patterns onto hydrogels using an automated
      drop-on-demand dispenser setup. Controlled by an image detection algorithm
      focusing the dispenser nozzle, droplets containing exactly one spheroid are
      printed onto a substrate, while all other droplets are discarded. Using this
      approach an array of 6 * 3 HUVEC spheroids with intermediate distances of 500 MUm
      embedded in fibrin was generated. Successful progress of spheroid sprouting and
      merging of neighboring sprouts was observed during the first 72 h of incubation
      indicating a good viability of the deposited spheroids.

PMID- 28488595
TI  - Ab initio prediction of the electronic, magnetic and topological properties of
      Ln2O3 clusters.
AB  - The structural, electronic and magnetic properties of the lanthanide oxide Ln2O3
      clusters, where Ln signifies lanthanides from La to Lu, have been calculated
      using spin-polarized density functional theory with the B3LYP hybrid functional.
      The intensities of ferromagnetic RKKY interaction are found comparable with that
      of antiferromagnetic superexchange interaction in Ce2O3 / Pr2O3 / Nd2O3 / Gd2O3 /
      Tb2O3 / Tm2O3 clusters, while the other Ln2O3 clusters prefer ferromagnetic
      states to antiferromagnetic states in energy, except nonmagnetic La2O3 and Lu2O3
      clusters. The theoretical spin magnetic moments, calculated three-dimensional
      spin density maps and dipole moments of Ln2O3 clusters suggest that the induced
      polarizations of oxygen atoms in Sm2O3, Eu2O3 and Yb2O3 clusters remarkably lead
      to the elongated Ln-O bond lengths in these clusters. The partial density of
      states of Ln2O3 clusters reveals that Sm3+ /Eu3+ /Yb3+ ions are distinctive from
      other Ln3+ ions in that their Ln-4f electrons are strongly hybrid with O-2 p
      electrons. The topological analysis of the electron density was also performed
      with quantum theory of atoms in molecules, which indicates the ionic Ln-O bonds
      have partial covalent characteristics.

PMID- 28488596
TI  - The impact of microfluidic mixing of triblock micelleplexes on in vitro / in vivo
      gene silencing and intracellular trafficking.
AB  - The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol (PEI
      PCL-PEG) has been shown to spontaneously assemble into nano-sized particulate
      carriers capable of complexing with nucleic acids for gene delivery. The
      objective of this study was to investigate micelleplex characteristics, their in
      vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles
      compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL
      PEG nanoparticles were prepared with batch reactor or microfluidic mixing
      techniques and characterized by various biochemical assays and in cell culture.
      Microfluidic nanoparticles showed a reduction of overall particle size as well as
      a more uniform size distribution when compared to batch reactor pipette mixing.
      Confocal microscopy, flow cytometry and qRT-PCR displayed the subcellular
      delivery of the microfluidic formulation and confirmed the ability to achieve
      mRNA knockdown. Intratracheal instillation of microfluidic formulation resulted
      in a significantly more efficient (p < 0.05) knockdown of GAPDH compared to
      treatment with the batch reactor formulation. The use of microfluidic mixing
      techniques yields an overall smaller and more uniform PEG-PCL-PEI nanoparticle
      that is able to more efficiently deliver siRNA in vivo. This preparation method
      may prove to be useful when a scaled up production of well-defined polyplexes is
      required.

PMID- 28488597
TI  - Electrohydrodynamics of a compound vesicle under an AC electric field.
AB  - Compound vesicles are relevant as simplified models for biological cells as well
      as in technological applications such as drug delivery. Characterization of these
      compound vesicles, especially the inner vesicle, remains a challenge. Similarly
      their response to electric field assumes importance in light of biomedical
      applications such as electroporation. Fields lower than that required for
      electroporation cause electrodeformation in vesicles and can be used to
      characterize their mechanical and electrical properties. A theoretical analysis
      of the electrohydrodynamics of a compound vesicle with outer vesicle of radius R
      o and an inner vesicle of radius [Formula: see text], is presented. A phase
      diagram for the compound vesicle is presented and elucidated using detailed plots
      of electric fields, free charges and electric stresses. The electrohydrodynamics
      of the outer vesicle in a compound vesicle shows a prolate-sphere and prolate
      oblate-sphere shape transitions when the conductivity of the annular fluid is
      greater than the outer fluid, and vice-versa respectively, akin to single vesicle
      electrohydrodynamics reported in the literature. The inner vesicle in contrast
      shows sphere-prolate-sphere and sphere-prolate-oblate-sphere transitions when the
      inner fluid conductivity is greater and smaller than the annular fluid,
      respectively. Equations and methodology are provided to determine the bending
      modulus and capacitance of the outer as well as the inner membrane, thereby
      providing an easy way to characterize compound vesicles and possibly biological
      cells.

PMID- 28488598
TI  - The cover page.

PMID- 28488599
TI  - Random reflections.

PMID- 28488600
TI  - Two founders of Bombay neurosciences: Dr. Ramchandra G. Ginde and Dr. Menino De
      Souza.

PMID- 28488601
TI  - 1892 and the tribulations of Joseph Babinski.
AB  - In the early 1880s, Joseph Babinski was appointed as Chef de Clinique under Jean
      Martin Charcot at Salpetriere, Paris, in France. He appeared for the post of
      Professeur Agrege, the pinnacle of academic distinction in France in 1892.
      Charles Bouchard, the earliest pupil of Charcot, who described the Charcot
      Bouchard aneurysm along with his master, was the Chief of the Board of Jury.
      Charcot and Bouchard did not see eye to eye in the later period, and when German
      See, an external examiner did not join the board of examiners following illness,
      Bouchard, instead of seeking the assistance of an alternate examiner, employed
      the special right of Vote of Absence. Babinski and all other pupils of Charcot
      were unsuccessful, while those of Bouchard, came out with flying colors. An
      embittered Babinski, along with some of the other unsuccessful candidates,
      appeared before the Ministry of Public Assistance after a protracted legal battle
      for nearly 2 years but lost the case. They were even ordered by the court to pay
      on behalf of the the successful candidates for the legal battle. Babinski never
      sat for the examination again and this is the story of one of the most
      ignominious episodes in an examination anywhere.

PMID- 28488602
TI  - Endoscopic management of intracranial cysts: Need of the hour.

PMID- 28488603
TI  - Role of neuro-endoscopy and fenestration in the management of brain cysts.

PMID- 28488604
TI  - Clinical and health policy-related challenges of pediatric spinal cord injuries.

PMID- 28488605
TI  - Surgical considerations in the management of pediatric thoracolumbar fractures.

PMID- 28488606
TI  - Pediatric thoracolumbar fractures: Salient points in management.

PMID- 28488607
TI  - Pediatric thoracolumbar spinal injuries: A rare and unique clinical scenario.

PMID- 28488608
TI  - Epilepsy surgery in children.
AB  - Approximately 60% of all patients with epilepsy suffer from focal epilepsy
      syndromes. In approximately 15% of these patients, the seizures are not
      adequately controlled with anticonvulsive drugs, and such patients are potential
      candidates for surgical treatment and majority are children. Epilepsy surgery in
      children, who have been carefully chosen, can result in either seizure freedom or
      a marked (>90%) reduction in seizures in approximately two-third of children with
      intractable seizures. In the multimodality presurgical evaluation approach,
      sufficient concordance should be established among various independent
      investigations, thus identifying the location and extent of the epileptogenic
      zone with a high degree of confidence. Early surgery improves the quality of life
      and cognitive and developmental outcome of the child. Surgically remediable
      epilepsies in children should be identified early and include temporal lobe
      epilepsy with focal lesions, lesional extratemporal epilepsies, hemispherical
      epilepsies, and gelastic epilepsy with hypothalamic hamartoma, and can be treated
      by resective or disconnection surgery. Palliative procedures include corpus
      callosotomy and vagal nerve stimulation for children with diffuse and multifocal
      epilepsies, who are not candidates for resective surgery. Deep brain stimulation
      in patients with epilepsy is still under evaluation. For children with
      "surgically remedial epilepsy," surgery should be offered as a procedure of
      choice rather than as a treatment of last resort.

PMID- 28488609
TI  - Microvascular decompression for hemifacial spasm: A systematic review of vascular
      pathology, long term treatment efficacy and safety.
AB  - INTRODUCTION: Hemifacial spasm (HS) is a rare disorder caused by the compression
      of facial nerve root exit zone (REZ) at the brainstem by a vascular loop.
      Microvascular decompression (MVD) is a popular treatment modality for HS.
      OBJECTIVE: The purpose of this study was to determine the long-term efficacy and
      safety of MVD for HS by assessing the effect of the procedure from the literature
      published over the last 25 years. MATERIALS AND METHODS: A systematic data review
      from 1992 to 2015 using specific eligibility criteria yielded 27 studies on MVD
      for HS, the data of which were pooled and subjected to a meta-analysis. RESULTS:
      The pooled odds ratio (OR) revealed by the meta-analysis showed that anterior
      inferior cerebellar artery was the most common offending vessel in 37.8% (95%
      confidence interval [CI]: 27.8-47.7%) of the patients. Complete resolution of HS
      was seen in 88.5% (95% CI: 86.7-90.4%) of the patients after a long-term follow
      up. The complication rate was low following MVD, the most common being temporary
      facial paresis in 5.9% (95% CI: 4.3-7.5%) of patients. CONCLUSIONS: MVD is a safe
      and effective treatment for HS with long-term benefits and a low complication
      rate.

PMID- 28488610
TI  - Pregabalin and lamotrigine in central poststroke pain: A pilot study.
AB  - BACKGROUND: Comparative study of Class I drugs in central poststroke pain (CPSP)
      is lacking. OBJECTIVE: To evaluate the safety and efficacy of pregabalin and
      lamotrigine in patients with CPSP. SETTING: Tertiary care teaching referral
      hospital. METHODS: We included consecutive patients with CPSP having >=50 mm
      score on Visual Analog Scale (VAS) and randomized them to receive either oral
      pregabalin or oral lamotrigine. Their clinical findings, serum chemistry, and
      cranial magnetic resonance imaging findings were noted. The severity of CPSP was
      assessed by VAS while the allodynia was assessed on a 0-10 scale. The hospital
      anxiety and depression (HAD) score was also recorded. The primary outcome was>
      50% reduction in the VAS score while the secondary outcome was> 50% reduction in
      the severity of allodynia and improvement in HAD score at 3 months. Adverse
      reactions were noted in both the groups. RESULTS: There were 30 patients with
      CPSP with a median age of 54.5 years (Male:Female = 36:4). While both pregabalin
      (P < 0.0001) and lamotrigine (P < 0.0001) resulted in significant improvement in
      the VAS score (63.3% vs. 53.3%), allodynia (66.7% vs. 75%), and HAD score (80%
      vs. 81.8%) compared to the baseline, the was no significant intergroup
      difference. Lamotrigine had to be withdrawn in three patients due to skin rash.
      CONCLUSIONS: Both pregabalin and lamotrigine are equally effective in CPSP, but
      significant side effects leading to drug withdrawal occured with lamotrigine
      administration.

PMID- 28488611
TI  - Deregulation of microRNAs in blood and skeletal muscles of myotonic dystrophy
      type 1 patients.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are short RNA molecules of approximately 22
      nucleotides that function as post-transcriptional regulators of gene expression.
      They are expressed in a tissue-specific manner and show different expression
      patterns in development and disease; hence, they can potentially act as disease
      specific biomarkers. Several miRNAs have been shown to be deregulated in plasma
      and skeletal muscles of myotonic dystrophy type 1 (DM1) patients. METHODS: We
      evaluated the expression patterns of 11 candidate miRNAs using quantitative real
      time PCR in whole blood (n = 10) and muscle biopsy samples (n = 9) of DM1
      patients, and compared them to those of normal control samples (whole blood, n =
      10; muscle, n = 9). RESULTS: In DM1 whole blood, miRNA-133a, -29b, and -33a were
      significantly upregulated, whereas miRNA-1, -133a, and -29c were significantly
      downregulated in the skeletal muscles compared to controls. CONCLUSIONS: Our
      findings align to those reported in other studies and point towards pathways that
      potentially contribute toward pathogenesis in DM1. However, the currently
      available data is not sufficient for these miRNAs to be made DM1-specific
      biomarkers because they seem to be common to many muscle pathologies. Hence, they
      lack specificity, but reinforce the need for further exploration of DM1
      biomarkers.

PMID- 28488612
TI  - Analysis of mortality and related factors in 2195 adult myasthenia gravis
      patients in a 10-year follow-up study.
AB  - OBJECTIVE: To analyze the mortality and potential risk factors for death in
      myasthenia gravis (MG) patients. MATERIALS AND METHODS: A total of 2195 adult
      patients with MG (aged older than 18 years) diagnosed during the period between
      2003 and 2013 were followed-up and retrospectively reviewed. RESULTS: During the
      10-year follow-up, 129 patients died and the total mortality rate was 5.88%. The
      risk factors associated with MG-related deaths were duration of the disease,
      occurrence of myasthenic crisis, severity of disease that included the Myasthenia
      Gravis Foundation of America (MGFA) grade III and IV at onset, elevation of
      acetylcholine receptor antibody (AchR-abs) titers, presence of thymic pathology,
      and failure of administrating immunosuppressants (P < 0.05). In addition, the non
      MG related factors, including the history of preceding strokes, and the presence
      of chronic obstructive pulmonary disease (COPD), diabetes mellitus, atrial
      fibrillation, hyperlipidemia, myocardial infarction, and malignant tumors, were
      closely linked with death in the MG population (the hazard ratios [HRs] were
      3.251, 4.173, 3.738, 3.886, 1.945, 2.177, and 14.7, respectively; P< 0.05).
      CONCLUSIONS: The severity of disease at entry, presence of AchRabs, thymic
      pathology, and duration of the disease predict a higher risk for death. Systemic
      illnesses including stroke, COPD, diabetes mellitus, atrial fibrillation,
      hyperlipidemia, myocardial infarction, and malignant tumor, which may also
      increase the risk of death, should be carefully monitored and managed.

PMID- 28488613
TI  - What kills a myasthenic? Myasthenia or otherwise.

PMID- 28488614
TI  - Safety and efficacy of therapeutic membrane plasmapheresis in the treatment of
      Guillain-Barre syndrome: A study from a tertiary care hospital from India.
AB  - BACKGROUND: Reports on therapeutic plasma exchange (TPE) with the standard
      hemodialysis equipment are scarce, particularly from developing countries.
      MATERIALS AND METHODS: A retrospective analysis of safety and efficacy of
      membrane-based TPE with a standard hemodialysis equipment for the treatment of
      severe Guillain-Barre syndrome (GBS) was conducted. RESULTS: A total of 120 TPE
      sessions were performed in 31 GBS patients over a period of 51/2 years. Each
      patient underwent a mean of 3.8 +/- 1.5 TPE sessions. One (3.2%) patient died.
      Thirty (96.8%) patients survived and recovered. At 2 weeks, there was a
      significant improvement in the grade of power in both the upper and lower
      extremities (P = 0.001) and a significant decrease in the GBS disability grade (P
      = 0.001). Twenty four (77.4%) patients were able to walk unaided. Complications
      observed were: hypotension in 12 (10%), accelerated hypertension in 3 (2.5%),
      chills and rigors in 5 (4.2%), bleeding in 5 (4.2%), and filter clotting in 6
      (5%) sessions. One patient experienced an anaphylactoid reaction and 1 patient
      survived a cardiorespiratory arrest. Two patients developed aspiration pneumonia
      and 1 patient developed catheter site infection. CONCLUSIONS: Membrane-based TPE
      can be conveniently delivered with the standard hemodialysis equipment. It is a
      safe, effective, and comparatively less expensive treatment option for GBS.

PMID- 28488615
TI  - Sensory tricks in primary blepharospasm and idiopathic cervical dystonia.
AB  - OBJECTIVE: To study the frequency, types, phenomenology, and effectiveness of
      sensory tricks in patients with primary blepharospasm and idiopathic cervical
      dystonia. BACKGROUND: Sensory tricks are maneuvers seen in patients with
      dystonia, which are used to temporarily reduce the severity of dystonic postures.
      In different types of dystonia, the frequency of sensory tricks have been
      described to range from 17-89%. MATERIALS AND METHODS: In this cross-sectional
      observational study, we analyzed the frequency, types, phenomenology, and
      effectiveness of sensory tricks in 20 patients with primary blepharospasm and 20
      patients with idiopathic cervical dystonia, respectively. Patients underwent a
      clinical examination, and the severity of dystonia was measured using the Burke
      Fahn Marsden dystonia rating scale (eyes and neck components).A questionnaire
      regarding the sensory tricks was administered to all the patients. RESULTS:
      Eighteen patients with blepharospasm and 7 patients with cervical dystonia used
      sensory tricks to alleviate their dystonic movements (P < 0.05). The age group of
      the patients with cervical dystonia presenting with sensory tricks was
      significantly lower than that of those having blepharospasm (P < 0.05). Sensory
      tricks, when used, were effective every time in 72.2% of patients with
      blepharospasm and in 85.8% of patients with cervical dystonia. However, majority
      of the patients with blepharospasm (61.1%) and cervical dystonia (42.9%) had only
      partial benefit (<50%) with these maneuvers. CONCLUSIONS: In this study, sensory
      tricks were more common in patients with primary blepharospasm than in patients
      with idiopathic cervical dystonia.Age of the patients with cervical dystonia was
      significantly lesser than those suffering from blepharospasm.We did not find any
      correlation between the presence of sensory tricks, the severity of dystonia and
      the duration of the disease.Majority of the patients derived benefit with sensory
      tricks every time; however, the benefit was only partial.

PMID- 28488616
TI  - Sensory tricks in dystonia: Phenomenology and mechanisms.

PMID- 28488617
TI  - Do the clinicoradiological outcomes of endoscopic fenestration for intracranial
      cysts count on age? An institutional experience.
AB  - BACKGROUND: The clinicoradiological outcome of endoscopic fenestration of
      intracranial cysts and predictors of an unfavorable outcome, including age, are
      under reported in the neurosurgical literature. In this cohort, our experience in
      the endoscopic fenestration of intracranial cysts is reviewed. MATERIALS AND
      METHODS: Thirty consecutive patients treated with endoscopic fenestration for
      intracranial cysts were identified and analyzed. The study population in our
      series was followed clinically and radiographically. RESULTS: In this series, the
      overall resolution of clinical symptoms such as headache, seizures, and
      neurological deficits was 83%, P= 0.0001. The percentage of clinical resolution
      after endoscopic intervention was significantly higher (85% vs. 76%, P= 0.001) in
      arachnoid cysts compared to other cyst types. The reduction of arachnoid cyst
      size was significantly higher in adults with obstructive hydrocephalus compared
      to the children group (P = 0.037). In addition, requirement of a cystoperitoneal
      shunt placement (P = 0.0001) and its subsequent revision (P = 0.0001) was
      significantly lower in adults compared to children. Adults (P = 0.041), presence
      of an arachnoid cyst (P = 0.026), female gender (P = 0.016), and presence of
      communicative hydrocephalus (P = 0.015) were significant predictors for
      improvement in the symptoms of intracranial pressure. Lastly, adults (P = 0.028),
      presence of arachnoid cyst (P = 0.046), and presence of communicative
      hydrocephalus (P = 0.012) were significant positive predictors for shunt
      revision. CONCLUSIONS: This study revealed that endoscopic fenestration is an
      effective neurosurgical procedure for the management of intracranial cysts both
      in adults and children. Moreover, endoscopic fenestration is more beneficial in
      adults and patients with an arachnoid cyst compared to that in children and other
      cyst types, respectively.

PMID- 28488618
TI  - Pediatric thoracolumbar spinal injuries: The etiology and clinical spectrum of an
      uncommon entity in childhood.
AB  - BACKGROUND: Pediatric thoracolumbar (TL) spinal injuries are uncommon entities
      with an incidence of 5-34% of all pediatric spinal injuries. There is a scarcity
      of studies done on the pediatric population in the developing countries like
      India. This study aims to review our experience with TL spine injuries in
      children over a 12-year period. MATERIALS AND METHODS: We retrospectively
      reviewed the epidemiology, risk factors, mechanisms, patterns of injury and
      management of pediatric TL injuries in our population. RESULTS: There were 90
      children with TL spine injuries comprising 2% of all the spine injuries treated
      in our institute. The mean age was 15.9 +/- 3.2 years (range: 2-18 years) with a
      male predominance (3:1). The most common mode of injury was fall from height.
      64/90 (71.1%) children sustained injury due to fall from height, 18/90 (20%)
      children sustained injury following motor vehicle accident and rest of the
      children sustained injury due to the fall of a heavy object over the neck. Most
      of the patients (27.8%) sustained Grade A injury. Lumbar spine was the most
      common spinal level injured (53.3%), and fractures were the most common type of
      injury (93.3%). Surgical fixation was performed in 18/90 (20%) children. Follow
      up was available for 21 children of which 13 (62%) were ambulant at follow-up.
      CONCLUSION: TL injuries are rare and are most common in children older than 10
      years and mainly involve the lumbar region. When indicated, surgical fusion of
      the involved vertebrae is safe and effective.

PMID- 28488620
TI  - Peripheral nerve injuries - A call for better evaluation and preventive measures.

PMID- 28488619
TI  - Peripheral nerve injuries: A retrospective survey of 1124 cases.
AB  - BACKGROUND: Peripheral nerve injuries (PNIs) remain an important health problem
      often leading to severe motor disabilities predominantly in the younger
      population. OBJECTIVE: To analyze our experience of clinical and
      electrodiagnostic evaluation (EDX) of PNIs over a 26-year period. MATERIALS AND
      METHODS: Between 1989 and 2014, 1124 consecutive patients with 1418 PNIs were
      referred for clinical as well as EDX evaluation. These PNIs involved upper and
      lower limbs as well as the facial nerves. Patients with iatrogenic lesions and
      spinal cord/spinal root lesions were excluded from this analysis. Brachial plexus
      (BP) injuries with associated or not with root avulsions were considered as one
      particular nerve and was include in the study as BP. The etiological categories
      of the sustained trauma included vehicular accidents, penetrating injuries,
      falls, gunshot wounds, car accidents involving pedestrians, sports injuries, and
      miscellaneous injuries. RESULTS: The mean age of our patients was 34.2 years and
      most were males (76.7%). Majority (80.9%) of the PNIs were isolated injuries.
      Combined lesions most commonly involved the ulnar and median nerves. Upper-limb
      PNIs accounted for 72.6% of our patients. The ulnar nerve was injured most often,
      either singly or in combination. Vehicular accidents were the most common causes
      of injury (46.4%), affecting the brachial BP or the radial, fibular, or sciatic
      nerves. Penetrating trauma (23.9%) commonly affected the ulnar and the median
      nerves. Falls and gunshot wounds frequently affected the ulnar, radial, and
      median nerves. Sports injuries, mostly soccer related, affected predominantly the
      fibular nerves. BP injuries were considerably more common in accidents involving
      motorcycles than those involving cars (46.1% vs. 17.1%), and root avulsions was
      more frequently associated in these cases. CONCLUSIONS: Most PNIs were caused by
      vehicular accidents and penetrating trauma, and affected young men. Overall,
      ulnar nerve, primary BP, and median nerve PNIs were the most prevalent lesions.

PMID- 28488621
TI  - Tumefactive acute disseminated encephalomyelitis.
AB  - Tumefactive demyelinating lesions are tumour-like presentations of acute
      demyelinating lesions. They have been described with multiple sclerosis only and
      not with other varieties of acquired demyelination like acute disseminated
      encephalomyelitis (ADEM). The uncertainty about the diagnosis at the onset of the
      disease in tumefactive ADEM makes it important that the physicians should be
      aware of this entity. Various radiological similarities with more sinister
      lesions like central nervous system gliomas or lymphomas may lead to this
      confusion. Appropriate supportive treatment with steroids and follow up is
      required in these cases to avoid unnecessary interventions.

PMID- 28488622
TI  - Family with Ehlers-Danlos syndrome (combined classic and vascular type) with rare
      presentation of progressive myopathy and unusual association of severe facial and
      trigeminal motor weakness.
AB  - We report the clinical, radiological, biochemical, muscle histology, and electron
      microscopic features of two members of a family with combined Ehlers-Danlos
      syndrome (EDS) [classic and vascular type] and progressive myopathy as the
      primary manifestation. A 35-year old lady presented with severe gluteal and thigh
      muscle pain and easy fatigability for 5 years. She developed weakness and wasting
      of pelvic and pectoral girdles and thighs for 3 years and severe neck flexor and
      truncal weakness for 6 months. She had a history of recurrent jaw dislocation,
      easy bruising with hyperpigmentation, hyperextensibility of joints, translucent
      skin, and papyraceous scars. She had high myopia with astigmatism. She had
      wasting of temporalis, masseters, sternocleidomastoids and trapezius. There was
      moderate weakness of temporalis, masseters, and facial muscles. Muscle power was
      Medical Research Council (MRC) grade 4 at shoulders and arms, and grade 3+ at
      pelvis and thighs. Serum homocysteine level was normal, and creatine kinase (CK)
      was 275 IU. Two dimensional echocardiogram (2D Echo) showed myxomatous
      degeneration of mitral valves. Electromyography (EMG) was suggestive of a
      myopathic pattern. Muscle magnetic resonance imaging (MR) revealed severe fatty
      infiltration of paraspinal muscles, gluteus maximus and medius, quadriceps,
      hamstrings, and gastrocnemius. Electron microscopy showed an occasional distorted
      fibril with mild increase in oxytalan fibers and variation in thickness of blood
      vessel basement membrane. Her 15-year old daughter had exertion-induced myalgias,
      right hemifacial hypoplasia, myopia, hyperextensible joints, hyperelastic skin,
      and neck muscle weakness. However, her CK and 2D Echo were normal. This report
      presents the rare combination of classic and vascular type of EDS primarily
      presenting as muscle weakness and associated with facial and trigeminal motor
      weakness.

PMID- 28488623
TI  - Endovascular pulmonary artery inflatable balloon-induced hypotension: A novel
      technique for clipping giant intracranial aneurysms.
AB  - Management of giant intracranial aneurysms presents unique challenges to the
      neurosurgical team. Various techniques such as adenosine-induced hypotension,
      rapid ventricular pacing, and inducing deep hypothermia are described in the
      literature to effect circulatory arrest for the successful obliteration of giant
      aneurysms. We describe a novel technique of induced hypotension for clipping a
      giant aneurysm by using an inflatable balloon across the main pulmonary artery
      with a successful outcome. This technique has not been described earlier in the
      literature.

PMID- 28488624
TI  - Papillary craniopharyngioma: A clinicopathologic study of a rare entity from a
      major tertiary care center in Pakistan.
AB  - BACKGROUND: Papillary craniopharyngioma (PCP) are uncommon variants of
      craniopharyngiomas (CP), which are benign epithelial neoplasms of the sellar and
      suprasellar region. Histologically, PCPs are typically composed of well
      differentiated stratified squamous epithelium; however, focal variations are not
      uncommon. A distinction from other lesions of the region, despite being difficult
      to achieve due to the overlapping radiological and clinical features, is
      important for adequate treatment to be administered. OBJECTIVE: Our aim was to
      study the clinical and histological features of PCP with emphasis on features
      that are helpful in its distinction from other lesions that are similar in
      appearance. MATERIALS AND METHODS: We reviewed 13 cases of PCP diagnosed in our
      institution between January 2010 and December 2015. RESULTS: The mean age at
      presentation was 30.76 years. Two of the patients belonged to the pediatric age
      group. Male-to-female ratio was 2.25:1. Suprasellar location (either alone or in
      combination with sellar region) was the most common tumor site. Microscopically,
      all of the cases showed stratified squamous epithelium with frequent
      pseudopapillae formation. Focal adamantinomatous epithelium and columnar
      epithelium with variable cilia and goblet cells were seen in 4 (30.7%) cases.
      Brain invasion was observed in 3 (23%) cases. Four patients died of their
      disease; 2 of the 7 patients with an available follow up, developed recurrences;
      and, 5 experienced severe postoperative morbidity. CONCLUSION: Majority of the
      PCPs exhibited typical features with minor variations. Knowledge of the
      variations in histologic features helps in reaching the correct diagnosis. These
      tumors can behave aggressively with a high recurrence rate and decreased overall
      survival.

PMID- 28488625
TI  - Genetics of pituitary adenomas.
AB  - Clinically relevant pituitary tumors presenting with altered hormonal secretion
      or mass effect represent a significant proportion of patients in endocrinology
      clinics. However, in recent years, these patients are also referred to clinical
      genetic services due to possible germline mutations causing syndromic or isolated
      pituitary adenomas. While somatic mutations have been identified in GNAS, USB8,
      PIK3CA, GPR101 and rarely in RAS, germline mutations have been identified in
      MEN1, cyclin dependent kinase inhibitor genes, AIP, DICER1, PRKAR1A, PRKACA, SDH
      genes and GPR101. In this review, we present a short overview of pituitary
      adenoma classifications, pituitary development and somatic and germline genetic
      changes identified in these adenomas.

PMID- 28488626
TI  - Surgery for superior hypophyseal artery aneurysms: A new classification and
      surgical considerations.
AB  - BACKGROUND: Superior hypophyseal artery (SHA) aneurysms form a unique subgroup of
      paraclinoid aneurysms having a propensity to grow to a large size in the
      suprasellar region resulting in compression of the optic nerve, chiasma, and/or
      tract. AIM: A new classification of SHA aneurysms is proposed that helps in
      identifying the surgical issues encountered during surgical clipping of these
      medially directed aneurysms located at different segments of the medial surface
      of the internal carotid artery (ICA). SETTINGS AND DESIGN: This descriptive study
      was conducted at a tertiary care university hospital. MATERIAL AND METHODS: In 14
      patients operated for a SHA (mean age: 49.43 +/- 11.28 years; presenting either
      with subarachnoid hemorrhage (n = 11; 78.57%) or mass effect (n = 3; 21.42%), 4
      parameters having a bearing on surgery [a. size: (small <1 cm n = 5, large 1-2.5
      cm n = 7, giant >2.5 cm n = 2); b. origin of SHA aneurysmal neck and direction of
      its fundus; c. relationship of the aneurysm to important neurovascular
      structures; and, d. whether the aneurysms were saccular or fusiform] were used to
      divide SHA aneurysms into 7 categories a. Antero-supero-medial (n = 2); b. Antero
      infero-medial (n = 1); c. Supero-medial (n = 3); d. Infero-medial (n = 3); e.
      Postero-medial (n = 2); f. Fusiform (n = 1); and, g. Giant (n = 2). Modified
      Rankin Scale (MRS) score was utilized to assess outcome [favorable: mRS 0-2;
      unfavorable: mRS 3-6] at discharge and follow up. RESULTS: Modified Hunt and Hess
      grade at admission was 0 = 3; I = 3; II = 3; III = 2; IV = 3 (favorable mRS: 10;
      71.42%; unfavorable mRS: 4; 28.57%); and, Fisher grade was I = 3; II = 6; III =
      2; IV = 3. Twelve patients required anterior clinoid process drilling/carotid
      collar opening to facilitate optic nerve mobilization, for proximal ICA control,
      and to assess the proximal part of the neck of aneurysm for aneurysmal clipping
      (n = 13) or wrapping (n = 1). Fenestrated clip was applied in 5 patients. In the
      supero-medial group (antero-supero-medial, supero-medial, and postero-supero
      medial), the aneurysmal fundus was found directly below the ipsilateral optic
      apparatus, elevating it; in the postero-supero-medial group, the fundus often lay
      in close proximity to A1 artery, Heubner's recurrent artery, ICA bifurcation, or
      dorsum sellae. Optic pathway, hypothalamic, and medial lenticulostriate
      perforators also required careful separation. Antero-infero-medial SHA aneurysm
      was hidden from view, embedded in the anterior wall of sella below tuberculum
      sellae. At a median follow-up of 17.5 +/- 26.78 months (range: 8-84 months), 9
      (64.28%) patients had a favorable mRS and 5 (35.71%) an unfavorable one.
      CONCLUSION: Systematically classifying SHA aneurysms and anticipating the
      surgical risk based upon their anatomical variations helps in achieving a good
      surgical outcome.

PMID- 28488627
TI  - Neurosurgery at the Bombay Hospital.
AB  - Neurosurgery at Bombay Hospital started in 1953 when Dr. Ram Ginde joined as the
      Honorary Neurosurgeon. Over the years, the Department of Neurosurgery has earned
      the reputation of providing contemporary medical services as well as of imparting
      excellent training to the neurosurgical residents. Professor S. N. Bhagwati
      started the prestigious annual 'Ginde oration' in 1991, that has been given by
      several illustrious orators from across the world and has become a precursor of
      various medical activities held thereafter. This article retraces the history and
      achievements of the Department of Neurosurgery, Bombay Hospital Institute of
      Medical Sciences, Mumbai, and also highlights the immense contributions made by
      its members in the field of Neurosurgery in India.

PMID- 28488628
TI  - A summary of some of the recently published, seminal papers in neuroscience.

PMID- 28488629
TI  - Severe hypoglycemia mimicking raised intracranial pressure - A word of caution.

PMID- 28488630
TI  - Brainstem infarct as a rare complication of coagulase-negative staphylococcus
      meningitis.

PMID- 28488631
TI  - Ruptured dissecting aneurysm of the recurrent artery of Heubner: Consideration of
      pathological findings.

PMID- 28488632
TI  - Ruptured intracranial tuberculous aneurysm, a rare complication of central
      nervous system tuberculosis- A report and review of literature.

PMID- 28488633
TI  - A report of whole-genome sequencing in neurologic Wilson's disease.

PMID- 28488634
TI  - Paroxysmal tonic spasms as an initial manifestation of neuromyelitis optica.

PMID- 28488635
TI  - Movement disorders in anti-NMDA receptor encephalitis.

PMID- 28488636
TI  - Catathrenia: A rare disorder presenting as daytime sleepiness and headache.

PMID- 28488637
TI  - Dengue fever triggering hemiconvulsion hemiplegia epilepsy in a child.

PMID- 28488638
TI  - A rare presentation of trigeminal neuralgia in lateral medullary syndrome.

PMID- 28488639
TI  - Alpha coma: A report.

PMID- 28488640
TI  - A rare case of Marchiafava-Bignami disease: Extracallosal lesions involving
      bilateral medipeduncle.

PMID- 28488641
TI  - Cerebral venous thrombosis due to pheochromocytoma in a patient with Von Hippel
      Lindau mutation.

PMID- 28488642
TI  - Post digital subtraction angiography parenchymal contrast staining mimicking the
      presence of a hemorrhage.

PMID- 28488643
TI  - Primary progressive freezing gait: Report of five cases.

PMID- 28488645
TI  - Post-discectomy annular pseudocyst: A rare cause of failed back syndrome.

PMID- 28488644
TI  - Medullomyoblastoma: A report of two cases.

PMID- 28488646
TI  - Primary intradural cervical spine melanocytoma: A rare tumor and review of
      literature.

PMID- 28488647
TI  - "Smart click" to the rescue of the patient's eye: Preventing compression on the
      globe during surgery in prone position using the selfie mode.

PMID- 28488648
TI  - A rare case of an internal acoustic meatal tuberculoma involving the VII-VIII
      nerve complex.

PMID- 28488649
TI  - Cost effective, technically simpler, and aesthetically promising cranioplasty in
      developing countries.

PMID- 28488650
TI  - Dorsolumbar spine Epstein Barr virus associated leiomyosarcoma in a human
      immunodeficiency virus patient.

PMID- 28488651
TI  - Successful management of a penetrating iron-rod injury through the oral cavity
      involving the posterior cranial fossa.

PMID- 28488652
TI  - Microcephaly with generalized dystonia: Exception to the rule.

PMID- 28488653
TI  - Dengue encephalitis: "Double doughnut" sign.

PMID- 28488654
TI  - Transcranial Doppler flow patterns in brain death: "Storm before the calm".

PMID- 28488655
TI  - Carbon monoxide toxicity: A reversible damage to brain.

PMID- 28488656
TI  - Humming bird sign, a significant sign.

PMID- 28488657
TI  - Central pontine myelinolysis associated with hypokalemia in a diabetic patient
      with sepsis.

PMID- 28488658
TI  - Walker-Warburg syndrome with gonadal dysgenesis: A rare association.

PMID- 28488659
TI  - Bilateral mirror image sphenoid wing meningiomas.

PMID- 28488660
TI  - Duplicated origin of vertebral artery.

PMID- 28488661
TI  - Dolichoectatic internal carotid artery presenting as a sellar-suprasellar mass
      with symptomatic hydrocephalus.

PMID- 28488662
TI  - Cerebral revascularization: The standard method of anastomosis or the newly
      recommended technique?

PMID- 28488663
TI  - Over-diagnosis of paroxysmal sympathetic hyperactivity.

PMID- 28488664
TI  - Author's Reply: Cerebral revascularization: Fundamental difference between the
      new and conventional technique.

PMID- 28488665
TI  - Clinicopathological conferences: The fading art of playing Sherlock Holmes.

PMID- 28488666
TI  - Stroke in children due to oral injury by a thread tied to a kite.

PMID- 28488667
TI  - Authors' Reply: Clinicopathological conferences: The fading art of playing
      Sherlock Holmes.

PMID- 28488668
TI  - Authors' Reply: Stroke in children due to an oral injury.

PMID- 28488669
TI  - Full-field perimetry in pituitary tumors.

PMID- 28488670
TI  - Authors' Reply: Comprehensive neuro-ophthalmological assessment in pituitary
      tumors.

PMID- 28488671
TI  - Actively addressed single pixel full-colour plasmonic display.
AB  - Dynamic, colour-changing surfaces have many applications including displays,
      wearables and active camouflage. Plasmonic nanostructures can fill this role by
      having the advantages of ultra-small pixels, high reflectivity and post
      fabrication tuning through control of the surrounding media. However, previous
      reports of post-fabrication tuning have yet to cover a full red-green-blue (RGB)
      colour basis set with a single nanostructure of singular dimensions. Here, we
      report a method which greatly advances this tuning and demonstrates a liquid
      crystal-plasmonic system that covers the full RGB colour basis set, only as a
      function of voltage. This is accomplished through a surface morphology-induced,
      polarization-dependent plasmonic resonance and a combination of bulk and surface
      liquid crystal effects that manifest at different voltages. We further
      demonstrate the system's compatibility with existing LCD technology by
      integrating it with a commercially available thin-film-transistor array. The
      imprinted surface interfaces readily with computers to display images as well as
      video.

PMID- 28488672
TI  - Large polarization gradients and temperature-stable responses in compositionally
      graded ferroelectrics.
AB  - A range of modern applications require large and tunable dielectric,
      piezoelectric or pyroelectric response of ferroelectrics. Such effects are
      intimately connected to the nature of polarization and how it responds to
      externally applied stimuli. Ferroelectric susceptibilities are, in general,
      strongly temperature dependent, diminishing rapidly as one transitions away from
      the ferroelectric phase transition (TC). In turn, researchers seek new routes to
      manipulate polarization to simultaneously enhance susceptibilities and broaden
      operational temperature ranges. Here, we demonstrate such a capability by
      creating composition and strain gradients in Ba1-xSrxTiO3 films which result in
      spatial polarization gradients as large as 35 MUC cm-2 across a 150 nm thick
      film. These polarization gradients allow for large dielectric permittivity with
      low loss (Er~775, tan delta<0.05), negligible temperature-dependence (13%
      deviation over 500  degrees C) and high-dielectric tunability (greater than 70%
      across a 300  degrees C range). The role of space charges in stabilizing
      polarization gradients is also discussed.

PMID- 28488673
TI  - Climate warming reduces the temporal stability of plant community biomass
      production.
AB  - Anthropogenic climate change has emerged as a critical environmental problem,
      prompting frequent investigations into its consequences for various ecological
      systems. Few studies, however, have explored the effect of climate change on
      ecological stability and the underlying mechanisms. We conduct a field experiment
      to assess the influence of warming and altered precipitation on the temporal
      stability of plant community biomass in an alpine grassland located on the
      Tibetan Plateau. We find that whereas precipitation alteration does not influence
      biomass temporal stability, warming lowers stability through reducing the degree
      of species asynchrony. Importantly, biomass temporal stability is not influenced
      by plant species diversity, but is largely determined by the temporal stability
      of dominant species and asynchronous population dynamics among the coexisting
      species. Our findings suggest that ongoing and future climate change may alter
      stability properties of ecological communities, potentially hindering their
      ability to provide ecosystem services for humanity.

PMID- 28488674
TI  - Corrigendum: Identification of RAN1 orthologue associated with sex determination
      through whole genome sequencing analysis in fig (Ficus carica L.).

PMID- 28488676
TI  - Introduction to the first ESHG/EJHG Anniversary issue.

PMID- 28488675
TI  - Comparison of the efficiency of colorectal cancer screening programs based on age
      and genetic risk for reduction of colorectal cancer mortality.
AB  - Given that colorectal cancer risk depends partly on inherited factors, screening
      program efficiency may be increased by incorporating genetic factors. We compared
      the efficiency of screening based on age and genetic risk in a simulated
      population. We simulated a population matching the size, age distribution and
      colorectal cancer incidence and mortality of Australia. We also simulated the
      distribution of genetic risk for colorectal cancer based on the expected number
      of inherited risk alleles of 45 single-nucleotide polymorphisms (SNPs) previously
      reported as associated with colorectal cancer. We compared the expected
      colorectal cancer deaths under three screening programs; age-based, genetic-based
      and combined age-based and genetic-based. The age-based program would prevent
      25.4 deaths per 100 000 invited to screen, none of which would be under age 50;
      the genetic program would prevent 26.2 deaths per 100 000 invited to screen, 16
      of which would be under age 50; and the combined program would prevent 24.4
      deaths per 100 000 invited to screen, 16 of which would be under age 50. Genetic
      testing of 1.5 million 45-49 year olds would identify 91% of the people aged
      under 50 at sufficient risk to warrant screening, potentially saving 16
      colorectal cancer deaths each year. Screening eligibility based on genetic risk
      profile for age is as efficient as eligibility based on age alone for preventing
      colorectal cancer mortality, but identifies an additional 7% of the population at
      sufficient risk to benefit from screening who would not normally be screened
      given they are aged under 50 years.

PMID- 28488677
TI  - Uninformed consent in nutrigenomic research.
AB  - Genetic testing for personalizing diet and wellness programs is performed without
      extensive counseling that informs about the potential implications of knowing
      one's genotype status. Genetic counseling seems redundant for genes that impact
      the effect of diet on biomarkers such as cholesterol and blood pressure, but the
      same genes may have pleiotropic effects that cannot be ignored. A well-known
      example is the APOE gene, which is implicated in cholesterol regulation and is a
      major risk factor for Alzheimer's disease. Not fully informing participants about
      the major pleiotropic effects of genes has ethical implications and invalidates
      informed consent.

PMID- 28488678
TI  - A missense variant in ITPR1 provides evidence for autosomal recessive SCA29 with
      asymptomatic cerebellar hypoplasia in carriers.
AB  - Spinocerebellar ataxias (SCA) comprise a heterogeneous group of inherited
      neurological disorders characterized by a range of symptoms from both cerebellar
      and extra cerebellar structures. We investigated the cause of autosomal
      recessive, congenital SCA in six affected family members from a large
      consanguineous family. Using whole-exome sequencing, we identified a homozygous
      ITPR1 missense variant [c.5360T>C; p.(L1787P)] segregating in all affected
      individuals. Heterozygous carriers were asymptomatic despite cerebellar
      hypoplasia. Variants in the ITPTR1 gene have previously been associated
      exclusively with autosomal dominant SCA15 and SCA29 with slow or no progression.
      The L1787 residue is highly conserved and the leucine to proline substitution has
      a predicted destabilizing effect on the protein structure. Additionally, the
      L1787P variant is located in a domain separated from previously described and
      dominant-acting missense variants consistent with a distinct effect on IP3R1
      tetramer structure and function. Taken together, we show for the first time that
      a biallelic ITPR1 missense variant may cause an autosomal recessive and infantile
      onset SCA29, albeit with subclinical cerebellar hypoplasia in carriers. Our
      findings add to the genetic complexity of SCA29 and broaden the correlations
      between ITPR1 variants and their clinical expression.

PMID- 28488679
TI  - The European Society of Human Genetics: beginnings, early history and development
      over its first 25 years.
AB  - The European Society of Human Genetics (ESHG) was founded on 15 March 1967, after
      preliminary discussions at the International Human Genetics Congress in Chicago
      the previous year and in Copenhagen in early 1967. Its initial meeting was held
      on 18-19 November 1967, also in Copenhagen, and annual meetings have been held
      from that time until the present, apart from years in which the International
      Congress of Human Genetics was also being held. The character of the Society
      during its early years was strongly influenced by its founding and permanent
      Secretary, Jan Mohr, head of the Copenhagen Institute of Medical Genetics, whose
      records are archived in the Tage Kemp/Jan Mohr Archive, now part of the Danish
      National Archives. These records show Jan Mohr's determination to keep the
      activities of the Society limited to the holding of an annual meeting to enhance
      contacts between European human geneticists, and to resist expansion to other
      activities. Pressures for a wider role of ESHG became irresistible in the late
      1980s and a revised constitution, adopted in 1991, reshaped the Society into a
      more conventional and less restrictive structure. This has allowed it to play a
      wider and increasingly influential role in the development of human and medical
      genetics across Europe, with its own Journal, a range of committees covering
      different aspects of the field and a series of valuable reports on specific
      important topics, to be described in a forthcoming article on the Society's more
      recent history.European Journal of Human Genetics advance online publication, 10
      May 2017; doi:10.1038/ejhg.2017.34.

PMID- 28488680
TI  - Some pioneers of European human genetics.
AB  - Some of the pioneers of human genetics across Europe are described, based on a
      series of 100 recorded interviews made by the author. These interviews, and the
      memories of earlier workers in the field recalled by interviewees, provide a
      vivid picture, albeit incomplete, of the early years of human and medical
      genetics. From small beginnings in the immediate post-World War 2 years, human
      genetics grew rapidly across many European countries, a powerful factor being the
      development of human cytogenetics, stimulated by concerns over the risks of
      radiation exposure. Medical applications soon followed, with the recognition of
      human chromosome abnormalities, the need for genetic counselling, the possibility
      of prenatal diagnosis and later, the applications of human molecular genetics.
      The evolution of the field has been strongly influenced by the characters and
      interests of the relatively small number of founding workers in different
      European countries, as well as by wider social, medical and scientific factors in
      the individual countries.European Journal of Human Genetics advance online
      publication, 10 May 2017; doi:10.1038/ejhg.2017.47.

PMID- 28488681
TI  - Practices and views of neurologists regarding the use of whole-genome sequencing
      in clinical settings: a web-based survey.
AB  - The use of Whole-Genome Sequencing (WGS) in clinical settings has brought up a
      number of controversial scientific and ethical issues. The application of WGS is
      of particular relevance in neurology, as many conditions are difficult to
      diagnose. We conducted a worldwide, web-based survey to explore neurologists'
      views on the benefits of, and concerns regarding, the clinical use of WGS, as
      well as the resources necessary to implement it. Almost half of the 204
      neurologists in the study treated mostly adult patients (48%), while the rest
      mainly children (37.3%), or both (14.7%). Epilepsy (73%) and headaches (57.8%)
      were the predominant conditions treated. Factor analysis brought out two
      profiles: neurologists who would offer WGS to their patients, and those who would
      not, or were not sure in which circumstances it should be offered. Neurologists
      considering the use of WGS as bringing more benefits than drawbacks currently
      used targeted genetic testing (P<0.05) or treated mainly children (P<0.05). WGS'
      benefits were directed towards the patients, while its risks were of a financial
      and legal nature. Furthermore, there was a correlation between respondents'
      current use of genetic tests and an anticipation of increased use in the future
      (P<0.001). However, over half of respondents did not feel sufficiently informed
      to use WGS in their practice (53.5%). Our results highlight gaps in education,
      organization, and funding to support the use of WGS in neurology, and draw
      attention to the need for resources that could strongly contribute to more
      straightforward diagnoses and possibly better treatment of neurological
      conditions.

PMID- 28488682
TI  - Exome sequencing revealed a splice site variant in the IQCE gene underlying post
      axial polydactyly type A restricted to lower limb.
AB  - Polydactyly is characterized by an extra supernumerary digit/toe with or without
      bony element. To date variants in four genes GLI3, ZNF141, MIPOL1 and PITX1 have
      been implicated in developing non-syndromic form of polydactyly. The present
      study involved characterization of large consanguineous family of Pakistani
      origin segregating post-axial polydactyly type A, restricted to lower limb, in
      autosomal recessive pattern. DNA of two affected members in the family was
      subjected to exome sequencing. Sanger sequencing was then followed to validate
      segregation of the variants in the family members. A homozygous splice acceptor
      site variant (c.395-1G>A) was identified in the IQCE gene, which completely co
      segregated with post-axial polydactyly phenotype within the family. The
      homozygous variant was absent in different public variant databases, 7000 in
      house exomes, 130 exomes from unrelated Pakistani individuals and 215 ethnically
      matched controls. Mini-gene splicing assay was used to test effect of the variant
      on function of the gene. The assay revealed loss of first nucleotide of exon 6,
      producing a -1 frameshift and a premature stop codon 22 bases downstream of the
      variant (p.Gly132Valfs*22). The study provided the first evidence of involvement
      of the IQCE gene in limbs development in humans.

PMID- 28488683
TI  - Progressive hereditary spastic paraplegia caused by a homozygous KY mutation.
AB  - Twelve individuals of consanguineous Bedouin kindred presented with autosomal
      recessive progressive spastic paraplegia evident as of age 0-24 months, with
      spasticity of lower limbs, hyperreflexia, toe walking and equinus deformity.
      Kyphoscolisois was evident in older patients. Most had atrophy of the lateral
      aspects of the tongue and few had intellectual disability. Nerve conduction
      velocity, electromyography and head and spinal cord magnetic resonance imaging
      were normal in tested subjects. Muscle biopsy showed occasional central nuclei
      and fiber size variability with small angular fibers. Genome-wide linkage
      analysis identified a 6.7Mbp disease-associated locus on chromosome 3q21.3-3q22.2
      (LOD score 9.02; D3S1290). Whole-exome sequencing identified a single homozygous
      variant within this locus, c.51_52ins(28); p.(V18fs56*) in KY, segregating in the
      family as expected and not found in 190 Bedouin controls. High KY transcript
      levels were demonstrated in muscular organs with lower expression in the CNS. The
      phenotype is reminiscent of kyphoscoliosis seen in Ky null mice. Two recent
      studies done independently and parallel to ours describe somewhat similar
      phenotypes in one and two patients with KY mutations. KY encodes a
      tranglutaminase-like peptidase, which interacts with muscle cytoskeletal proteins
      and is part of a Z-band protein complex, suggesting the disease mechanism may
      resemble myofibrillar myopathy. However, the mixed myopathic-neurologic features
      caused by human and mouse Ky mutations are difficult to explain by loss of KY
      sarcomere stabilizing function alone. KY transcription in CNS tissues may imply
      that it also has a role in neuromotor function, in line with the irregularity of
      neuromuscular junction in Ky null mutant mice.

PMID- 28488684
TI  - The impact of cholecalciferol supplementation on the systemic inflammatory
      profile: a systematic review and meta-analysis of high-quality randomized
      controlled trials.
AB  - Causal links between vitamin D status [25(OH)D] and systemic inflammation were
      examined through a systematic review of randomized controlled trials (RCTs).
      Selected RCTs were ?12 weeks, conducted in adults free of acute inflammatory
      disease, and of high-quality (Jadad score ?3). Of 14 studies that met our
      criteria, 9 studies (15 study arms) permitted extraction of data. There was no
      effect on the weighted mean difference (WMD) of IL-6 (WMD (95% confidence
      interval)=0.1, (-0.166, 0.366) pg/ml, P=0.462) or C-reactive protein (CRP) (WMD=
      0.324, (-1.007, 0.359) mg/l, P=0.352). Subgroup analyses of trials achieving ?80
      nmol/l indicated a trend for lower CRP (WMD=-0.834, (-1.726, 0.058) mg/l,
      P=0.067), however heterogeneity was significant (I2=66.7%, P=0.017). Studies
      employing a low dose (<1000 IU/d) showed increased CRP (WMD=0.615, (0.132,
      1.098), P=0.013). In contrast, ?1000 IU/d had a favourable effect on CRP (WMD=
      0.939, (-1.805, -0.073), P=0.034) but heterogeneity was significant (I2=61.3%,
      P=0.017). Meta-regression indicated that older age predicted a significant
      decrease in IL-6 (beta=-0.02, (-0.034, -0.006) pg/ml, P=0.013) and CRP (beta=
      0.06, (-0.103, -0.017), P=0.01), whereas a greater percentage of females
      (beta=0.027, (0.011, 0.044), P=0.004) and longer study duration independently
      predicted a higher WMD for CRP (beta=0.049, (0.018, 0.079), P=0.005). Available
      high-quality RCTs did not support a beneficial effect of cholecalciferol on
      systemic IL-6 and CRP. Future studies should consider the confounding effects of
      age, gender and study duration, while possibly targeting an achieved 25(OH)D ?80
      nmol/l.

PMID- 28488685
TI  - Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids
      and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma
      lipoprotein profiles.
AB  - BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution
      and concentration) play an important role in the pathobiology of atherosclerosis
      and coronary artery disease. Dietary fat, among other factors, has been
      demonstrated to modulate lipoprotein profiles. We aimed to investigate if
      background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty
      acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on
      lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical
      intervention trial in a parallel design was conducted. Healthy subjects (n=26)
      were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic
      acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a
      period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of
      intervention, were assessed for plasma lipoprotein profiles (lipoprotein size,
      concentration and distribution in subclasses) determined using nuclear magnetic
      resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n
      6PUFA enriched diets consumed similar percentage energy from fat (41 and 42%
      respectively, P=0.681). However, subjects on the SFA diet consumed 50% more
      energy as saturated fat and 77% less as linoleic acid than those consuming the n
      6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration
      of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their
      subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL
      (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride
      concentration was significantly reduced by LCn-3PUFA supplementation irrespective
      of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a
      similar fashion when supplemented in diets rich in either SFA or n-6PUFA.

PMID- 28488686
TI  - An overview of folate status in a population-based study from Sao Paulo, Brazil
      and the potential impact of 10 years of national folic acid fortification policy.
AB  - BACKGROUND/OBJECTIVES: Food fortification is an important strategy in public
      health policy for controlling micronutrient malnutrition and a major contributing
      factor in the eradication of micronutrients' deficiencies. Approximately 50
      countries worldwide have adopted food fortification with folic acid (FA). FA
      fortification of wheat and maize flours has been mandatory in Brazil since 2004.
      To assess the effect of 10 years of FA food fortification policy on folate status
      of residents of Sao Palo, Brazil using a population-based survey.
      SUBJECTS/METHODS: Data were from 750 individuals aged ?12 years who participated
      in a cross-sectional population-based survey in Sao Paulo city, Brazil. Fasting
      blood samples were collected, and folate was assayed by affinity-high performance
      liquid chromatografy method with electrochemical detection. The participants
      provided information about food intake based on two 24 h dietary recall. RESULTS:
      Only 1.76% of population had folate deficiency (<6.8 nmol/l). The mean folate
      concentration was 29.5 (95% confidence interval: 27.3-31.7) nmol/l for all sex
      age groups. The mean folate intake for the population was 375.8 (s.e.m.=6.4)
      MUg/day of dietary folate equivalents (DFEs). When comparing folate intake in DFE
      from food folate and FA from fortified foods, FA contributed 50% or more of the
      DFE in almost all sex-age groups. The major contributors of folate intake are
      processed foods made from wheat flour fortified with FA, especially among
      subjects younger than 20 years old. CONCLUSIONS: The deficiency of folate is very
      low, and food fortification contributed to folate intake and had a notable
      influence on rankings of food contributors of folate.

PMID- 28488687
TI  - Does diet intervention in line with nutrition recommendations affect dietary
      carbon footprint? Results from a weight loss trial among lactating women.
AB  - BACKGROUND/OBJECTIVES: Results from studies evaluating the sustainability of
      diets combining environmental and nutritional aspects have been diverse; thus,
      greenhouse gas emissions (that is, carbon footprint (CF)) of diets in line with
      dietary recommendations in free-living individuals warrants further examination.
      Here, changes in dietary CF related to changes in food choice during a weight
      loss trial among lactating women who received a 12-week diet intervention based
      on the Nordic Nutrition Recommendations (NNR) 2004 were analyzed. The objective
      of this study was to examine if a diet intervention based on NNR 2004 results in
      reduced dietary CF. SUBJECTS/METHODS: Changes in dietary CF were analyzed among
      61 lactating women participating in a weight loss trial. Food intake data from 4
      day weighed diet records and results from life cycle analyses were used to
      examine changes in dietary CF across eight food groups during the intervention,
      specified in the unit carbon dioxide equivalent (CO2eq/day). Differences in
      changes in dietary CF between women receiving diet treatment (D-group) and women
      not receiving it (ND-group) were compared. RESULTS: There was no difference in
      change in dietary CF of the overall diet between D- and ND-group (P>0.05). As for
      the eight food groups, D-group increased their dietary CF from fruit and
      vegetables (+0.06+/-0.13 kg CO2eq/day) compared with a decrease in ND-group (
      0.01+/-0.01 kg CO2eq/day) during the intervention, P=0.01. CONCLUSIONS: A diet
      intervention in line with NNR 2004 produced clinically relevant weight loss, but
      did not reduce dietary CF among lactating women with overweight and obesity.
      Dietary interventions especially designed to decrease dietary CF and their
      coherence with dietary recommendations need further exploration.

PMID- 28488688
TI  - Association between coffee or tea drinking and Barrett's esophagus or
      esophagitis: an Italian study.
AB  - BACKGROUND/OBJECTIVES: Only a few papers have treated of the relationship between
      Barrett's esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We
      evaluated the role of these beverages in BE and E occurrence. SUBJECTS/METHODS:
      Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee
      and tea and other individual characteristics were collected using a structured
      questionnaire. RESULTS: BE risk was higher in former coffee drinkers,
      irrespective of levels of exposure (cup per day; ?1: OR=3.76, 95% CI 1.33-10.6;
      >1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was
      higher with duration (>30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for
      late quitters, respectively (?3 years from cessation: OR=5.95, 95% CI 2.19-16.2;
      TLT P<0.001). The risk of BE was also higher in subjects who started drinking
      coffee later (age >18 years: OR=6.10, 95% CI 2.15-17.3). No association was found
      in current drinkers, but for an increased risk of E in light drinkers (<1 cup per
      day OR =1.85, 95% CI 1.00-3.43).A discernible risk reduction of E (about 20%, not
      significant) and BE (about 30%, P<0.05) was observed in tea drinkers.
      CONCLUSIONS: Our data were suggestive of a reduced risk of BE and E with tea
      intake. An adverse effect of coffee was found among BE patients who had stopped
      drinking coffee. Coffee or tea intakes could be indicative of other lifestyle
      habits with protective or adverse impact on esophageal mucosa.

PMID- 28488689
TI  - Effects of vitamin D or its analogues on the mortality of patients with chronic
      kidney disease: an updated systematic review and meta-analysis.
AB  - The objective of this study was to assess whether vitamin D (VD) treatment alters
      the overall all-cause and cardiovascular mortalities in a chronic kidney disease
      (CKD) population. We systematically searched PubMed, EMBASE, Web of Science, and
      Cochrane Central Register of Controlled Trials without language restriction,
      until the publication date of 22 February 2016. All related literatures that
      compared VD treatment with non-VD treatment and reported the mortality of
      patients with CKD (including those undergoing dialysis) were identified. Pooled
      risk ratios (RR) and 95% confidence intervals (CI) were calculated by using the
      random- and fixed-effects models. Randomised controlled trials (RCTs) that used
      the intention-to-treat principle and observational studies (OSs) were analysed
      separately. For this study, 38 studies involving 223 429 patients (17 RCTs,
      n=1819 and 21 OSs, n=221610) were included. In the OSs, VD treatment was
      significantly associated with reductions in both all-cause and cardiovascular
      mortalities; however, such significant association was not found in the RCTs. The
      existing RCTs do not provide sufficient or precise evidence that VD
      supplementation affects the mortality of patients with CKD, although subsets of
      patients that could potentially benefit from VD treatment can be identified by
      using the existing data from the RCTs. Nevertheless, large-size RCTs are needed
      in the future to assess any potential differences in survival prospectively.

PMID- 28488690
TI  - Soyfood and isoflavone intake and risk of type 2 diabetes in Vietnamese adults.
AB  - BACKGROUND/OBJECTIVES: Animal studies have demonstrated that soy isoflavones
      exert antidiabetic effects. However, evidence regarding the association between
      soyfood intake, a unique source of isoflavones, and type 2 diabetes remains
      inconclusive. This study assessed the relationship between habitual intakes of
      soyfoods and major isoflavones and risk of type 2 diabetes in Vietnamese adults.
      SUBJECTS/METHODS: A hospital-based case-control study was conducted in Vietnam
      during 2013-2015. A total of 599 newly diagnosed diabetic cases (age 40-65 years)
      and 599 hospital-based controls, frequency matched by age and sex, were recruited
      in Hanoi, capital city of Vietnam. Information on frequency and quantity of
      soyfood and isoflavone intake, together with demographics, habitual diet and
      lifestyle characteristics, was obtained from direct interviews using a validated
      and reliable questionnaire. Unconditional logistic regression analyses were
      performed to examine the association between soy variables and type 2 diabetes
      risk. RESULTS: Higher intake of total soyfoods was significantly associated with
      a lower risk of type 2 diabetes; the adjusted odds ratio (OR) for the highest
      versus the lowest intake was 0.31 (95% confidence interval (CI): 0.21-0.46;
      P<0.001). An inverse dose-response relationship of similar magnitude was also
      observed for total isoflavone intake (OR: 0.35; 95% CI: 0.24 to 0.49; P<0.001).
      In addition, inverse associations of specific soyfoods (soy milk, tofu and mung
      bean sprout) and major isoflavones (daidzein, genistein and glycitein) with the
      type 2 diabetes risk were evident. CONCLUSIONS: Soyfood and isoflavone intake was
      associated with a lower type 2 diabetes risk in Vietnamese adults.

PMID- 28488691
TI  - Interaction effect of PGC-1alpha rs10517030 variants and energy intake in the
      risk of type 2 diabetes in middle-aged adults.
AB  - BACKGROUND/OBJECTIVES: PGC-1alpha is an important regulatory factor for energy
      and glucose metabolism. Therefore, we investigated whether the PGC-1alpha
      genotype (rs10517030 and rs10212638) affects the incidence of type 2 diabetes
      mellitus (T2DM) and sought to explain the interactions between their variants and
      nutrient intake on the development of T2DM. SUBJECTS/METHODS: Subjects aged 40-65
      years of both genders were from the Ansung/Ansan cohorts (8842 adults) in Korea.
      Associations of PGC-1alpha variants rs10517030 and rs10212638 with T2DM were
      analyzed in a dominant genetic model, and were tested for interactions of
      genotypes and nutrients with T2DM risk. It was adjusted for covariates related to
      glucose metabolism. RESULTS: Three variants, rs10517030, rs10517032 and
      rs10212638, were positively associated with T2DM prevalence. Single-nucleotide
      polymorphisms, rs10517030 and rs10517032, had strong association (r2=0.963). In
      the glucose tolerance tests, odds ratios (ORs) for serum glucose levels at 120
      min were higher for subjects who were in the minor-allele group (minor allele
      homozygotes and heterozygotes) than for the major-allele group (major allele
      homozygotes) for rs10517030 variants. Serum insulin levels at 60 min had a lower
      ORs in the minor-allele group of rs10517030 variants. The interaction between
      energy intake and PGC-1alpha rs10517030 variants also affected T2DM risk. PGC
      1alpha minor alleles were linked to T2DM prevalence and homeostasis model
      assessment estimate of insulin resistance (HOMA-IR) only in the low-energy
      groups, and HOMA-B was significantly negatively associated with the minor-allele
      group of PGC-1alpha rs10517030 variants, only in the low-energy-intake groups.
      CONCLUSIONS: These data suggest that Koreans with the minor alleles of PGC-1alpha
      rs10517030, rs10517032 and rs10212638 are at greater risk of T2DM, and that a low
      energy diet is more protective against the development of T2DM in subjects with
      the major alleles of rs10517030 and rs10517032.

PMID- 28488692
TI  - Mediterranean diet and multiple health outcomes: an umbrella review of meta
      analyses of observational studies and randomised trials.
AB  - Research has shown that a greater adherence to the Mediterranean diet is
      associated with a reduced risk of major chronic disease. However, the existing
      literature leads to debate for different issues, such as the measurement of the
      adherence to the Mediterranean diet, the use of a wide variety of dietary indices
      with various food components and the large heterogeneity across the studies. In
      order to summarise the evidence and evaluate the validity of the association
      between the adherence to the Mediterranean diet and multiple health outcomes, an
      umbrella review of the evidence across meta-analyses of observational studies and
      randomised clinical trials (RCTs) was performed. Thirteen meta-analyses of
      observational studies and 16 meta-analyses of RCTs investigating the association
      between the adherence to the Mediterranean diet and 37 different health outcomes,
      for a total population of over than 12 800 000 subjects, were identified. A
      robust evidence, supported by a P-value<0.001, a large simple size, and not a
      considerable heterogeneity between studies, for a greater adherence to the
      Mediterranean diet and a reduced the risk of overall mortality, cardiovascular
      diseases, coronary heart disease, myocardial infarction, overall cancer
      incidence, neurodegenerative diseases and diabetes was found. For most of the
      site-specific cancers, as well as for inflammatory and metabolic parameters, the
      evidence was only suggestive or weak and further studies are needed to draw
      firmer conclusions. No evidence, on the other hand, was reported for bladder,
      endometrial and ovarian cancers, as well as for LDL (low density lipoprotein)
      cholesterol levels.

PMID- 28488693
TI  - ICOS protects against mortality from acute lung injury through activation of IL
      5+ ILC2s.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing
      irreversible lung scarring and loss of pulmonary function. IPF Patients suffer
      from a high rate of pulmonary infections and acute exacerbations of disease that
      further contribute to pulmonary decline. Low expression of the inducible T-cell
      costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts
      decreased survival of IPF patients, but the mechanisms by which ICOS protects are
      unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now
      demonstrate that ICOS expression enhances survival from lung injury rather than
      regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes
      (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion
      is ICOS dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in
      lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s,
      was significantly reduced after lung injury in ICOS-/- mice, and strikingly,
      treatment with IL-5 protected both ICOS-/- and wild-type mice from mortality.
      These results imply that low ICOS expression and decreased lung ILC2s in IPF
      patients may contribute to poor recovery from infections and acute exacerbation
      and that IL-5 treatment may be a novel therapeutic strategy to overcome these
      defects and protect against lung injury.

PMID- 28488694
TI  - Light-induced unfolding and refolding of supramolecular polymer nanofibres.
AB  - Unlike classical covalent polymers, one-dimensionally (1D) elongated
      supramolecular polymers (SPs) can be encoded with high degrees of internal order
      by the cooperative aggregation of molecular subunits, which endows these SPs with
      extraordinary properties and functions. However, this internal order has not yet
      been exploited to generate and dynamically control well-defined higher-order
      (secondary) conformations of the SP backbone, which may induce functionality that
      is comparable to protein folding/unfolding. Herein, we report light-induced
      conformational changes of SPs based on the 1D exotic stacking of hydrogen-bonded
      azobenzene hexamers. The stacking causes a unique internal order that leads to
      spontaneous curvature, which allows accessing conformations that range from
      randomly folded to helically folded coils. The reversible photoisomerization of
      the azobenzene moiety destroys or recovers the curvature of the main chain, which
      demonstrates external control over the SP conformation that may ultimately lead
      to biological functions.

PMID- 28488695
TI  - Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced
      immunologic dormancy of tumor-repopulating cells.
AB  - Interactions with the immune system may lead tumorigenic cells into dormancy.
      However, the underlying molecular mechanism is poorly understood. Using a 3D
      fibrin gel model, we show that IFN-gamma induces tumour-repopulating cells (TRCs)
      to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)
      aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-gamma
      signalling triggers differentiated tumour cell apoptosis via STAT1; however, when
      IDO1 and AhR are highly expressed as in TRCs, IFN-gamma results in IDO1/AhR
      dependent p27 induction that prevents STAT1 signalling, thus suppressing the
      process of cell death and activating the dormancy program. Blocking the IDO/AhR
      metabolic circuitry not only abrogates IFN-gamma-induced dormancy but also
      results in enhanced repression of tumour growth by IFN-gamma-induced apoptosis of
      TRCs both in vitro and in vivo. These data present a previously unrecognized
      mechanism of inducing TRC dormancy by IFN-gamma, suggesting a potential effective
      cancer immunotherapeutic modality through the combination of IFN-gamma and
      IDO/AhR inhibitors.

PMID- 28488696
TI  - Functional roles of cadherin, aminopeptidase-N and alkaline phosphatase from
      Helicoverpa armigera (Hubner) in the action mechanism of Bacillus thuringiensis
      Cry2Aa.
AB  - A pyramid strategy combining the Cry1A and Cry2A toxins in Bt crops has been
      widely used throughout the world to delay pest adaption to transgenic crops and
      broaden the insecticidal spectrum. Midgut membrane-bound cadherin (CAD),
      aminopeptidase-N (APN) and alkaline phosphatase (ALP) are important for Cry1A
      toxicity in some lepidopteran larvae, but the proteins that bind Cry2A in the
      midgut of target insects and their role in the Cry2A mechanism of action are
      still unclear. In this study, we found that heterologously expressed CAD, APN4
      and ALP2 peptides from the midgut of Helicoverpa armigera could bind to the
      Cry2Aa toxin with a high affinity. Additionally, the efficiency of Cry2Aa
      insecticidal activity against H. armigera larvae was obviously reduced after the
      genes encoding these proteins were silenced with specific siRNAs: CAD- and ALP2
      silenced larvae showed significantly similar reductions in mortality due to the
      Cry2Aa toxin (41.67% and 43.06%, respectively), whereas a larger reduction in
      mortality was observed in APN4-silenced larvae (61.11%) than in controls. These
      results suggest that CAD, APN4 and ALP2 are involved in the mechanism of action
      of Cry2Aa in H. armigera and may play important functional roles in the toxicity
      of the Cry2Aa toxin.

PMID- 28488697
TI  - Selective C70 encapsulation by a robust octameric nanospheroid held together by
      48 cooperative hydrogen bonds.
AB  - Self-assembly of multiple building blocks via hydrogen bonds into well-defined
      nanoconstructs with selective binding function remains one of the foremost
      challenges in supramolecular chemistry. Here, we report the discovery of a
      enantiopure nanocapsule that is formed through the self-assembly of eight amino
      acid functionalised molecules in nonpolar solvents through 48 hydrogen bonds. The
      nanocapsule is remarkably robust, being stable at low and high temperatures, and
      in the presence of base, presumably due to the co-operative geometry of the
      hydrogen bonding motif. Thanks to small pore sizes, large internal cavity and
      sufficient dynamicity, the nanocapsule is able to recognize and encapsulate large
      aromatic guests such as fullerenes C60 and C70. The structural and electronic
      complementary between the host and C70 leads to its preferential and selective
      binding from a mixture of C60 and C70.

PMID- 28488698
TI  - The Rhizobium tropici CIAT 899 NodD2 protein regulates the production of Nod
      factors under salt stress in a flavonoid-independent manner.
AB  - In the symbiotic associations between rhizobia and legumes, NodD promotes the
      expression of the nodulation genes in the presence of appropriate flavonoids.
      This set of genes is implied in the synthesis of Nodulation factors, which are
      responsible for launching the nodulation process. Rhizobium tropici CIAT 899 is
      the most successful symbiont of Phaseolus vulgaris and can nodulate a variety of
      legumes. This strain produces Nodulation factors under abiotic stress such as
      acidity or high concentration of salt. Genome sequencing of CIAT 899 allowed the
      identification of five nodD genes. Whereas NodD1 is essential to nodulate
      Leucaena leucocephala, Lotus japonicus and Macroptilium atropurpureum, symbiosis
      with P. vulgaris and Lotus burtii decreased the nodule number but did not abolish
      the symbiotic process when NodD1 is absent. Nodulation factor synthesis under
      salt stress is not regulated by NodD1. Here we confirmed that NodD2 is
      responsible for the activation of the CIAT 899 symbiotic genes under salt stress.
      We have demonstrated that NodD1 and NodD2 control the synthesis of the Nod factor
      necessary for a successful symbiosis with P. vulgaris and L. burtii. This is the
      first time that NodD is directly implied in the activation of the symbiotic genes
      under an abiotic stress.

PMID- 28488699
TI  - Charting the unknown epitranscriptome.
AB  - RNA modifications can alter RNA structure-function relationships and various
      cellular processes. However, the genomic distribution and biological roles of
      most RNA modifications remain uncharacterized. Here, we propose using phage
      display antibody technology and direct sequencing through nanopores to facilitate
      systematic interrogation of the distribution, location and dynamics of RNA
      modifications.

PMID- 28488701
TI  - RNA decay: The anti-apoptotic function of ADAR1.

PMID- 28488700
TI  - Alternative splicing as a regulator of development and tissue identity.
AB  - Alternative splicing of eukaryotic transcripts is a mechanism that enables cells
      to generate vast protein diversity from a limited number of genes. The mechanisms
      and outcomes of alternative splicing of individual transcripts are relatively
      well understood, and recent efforts have been directed towards studying splicing
      networks. It has become apparent that coordinated splicing networks regulate
      tissue and organ development, and that alternative splicing has important
      physiological functions in different developmental processes in humans.

PMID- 28488702
TI  - Mechanisms of diseases: Excessive polyQ tracts curb autophagy.

PMID- 28488704
TI  - Targeting curcumin to specific tumour cell environments: the influence of
      ancillary ligands.
AB  - Tumour-activation of prodrugs has the potential to improve the efficacy of
      anticancer agents while minimising systemic toxicity. Cobalt complexes are of
      interest in this respect as chaperones to deliver and release anticancer agents
      in the low oxygen, reducing environment of solid tumours. In addition to being
      able to release a cytotoxic ligand under the conditions of the tumour
      microenvironment, it is fundamental that the chaperone complex must also be able
      to penetrate through multiple cell layers to deliver the cytotoxin to all regions
      of the tumour. Herein, we report an investigation of the distribution and
      metabolism of two chaperone complexes of the anticancer agent curcumin within
      monolayer tumour cells and multicellular tumour spheroids. Using a combination of
      X-ray fluorescence microscopy, confocal fluorescence microscopy, and X-ray
      absorption spectroscopy, we demonstrate how the nature of the chaperone complex
      can profoundly influence the cellular uptake, distribution, and release mechanism
      of curcumin, providing key insights into the design of this class of prodrug.

PMID- 28488705
TI  - Ni/Co/Ti layered double hydroxide for highly efficient photocatalytic degradation
      of Rhodamine B and Acid Red G: a comparative study.
AB  - Optically responsive, luminescent Ni/Co/Ti layered double hydroxide (LDH),
      synthesized by a single step hydrothermal route, exhibits highly efficient
      photodegradation of cationic and anionic dyes, Rhodamine B (~99.8%) and Acid Red
      G (~99.6%) respectively, better than that of commercial catalysts like NiO, CoO
      and TiO2. The LDH has been characterized by using XRD, XPS, PL, TRES, EIS, TEM,
      SEM-EDX, AFM, UV-visible DRS, N2-sorption desorption, xi-potential, FT-IR and TG
      techniques. The characterized results indicate that the LDH possesses hexagonal
      morphology, a high surface area, a narrow band gap, defect states and oxygen
      vacancies within its layered framework. The degradations follow the e--h+ hopping
      pattern and dye-photosensitized mechanistic pathways. The active species
      generated during photocatalysis have been evaluated using ESR, terephthalic acid
      fluorescence probe and indirect radical-hole trapping experiments. The colourless
      end products were investigated by GC-MS and reaction mechanisms have been
      established for the degradation of the dyes to less toxic and more eco-friendly
      molecules than their parent analogues. Dye mineralization studies (performed
      using a TOC analyser) and closure of carbon mass balance experiments quantified
      the amount of carbon entering and leaving the reaction systems. Reaction
      mechanisms have been proposed on the basis of the asymmetric cleavage of the
      dyes. The LDH demonstrated its remarkable efficiency in the field of waste water
      treatment.

PMID- 28488703
TI  - Protein O-GlcNAcylation: emerging mechanisms and functions.
AB  - O-GlcNAcylation - the attachment of O-linked N-acetylglucosamine (O-GlcNAc)
      moieties to cytoplasmic, nuclear and mitochondrial proteins - is a post
      translational modification that regulates fundamental cellular processes in
      metazoans. A single pair of enzymes - O-GlcNAc transferase (OGT) and O-GlcNAcase
      (OGA) - controls the dynamic cycling of this protein modification in a nutrient-
      and stress-responsive manner. Recent years have seen remarkable advances in our
      understanding of O-GlcNAcylation at levels that range from structural and
      molecular biology to cell signalling and gene regulation to physiology and
      disease. New mechanisms and functions of O-GlcNAcylation that are emerging from
      these recent developments enable us to begin constructing a unified conceptual
      framework through which the significance of this modification in cellular and
      organismal physiology can be understood.

PMID- 28488706
TI  - Impact of aryloxy initiators on the living and immortal polymerization of
      lactide.
AB  - This report describes two different methodologies for the synthesis of aryl end
      functionalized poly(lactide)s (PLAs) catalyzed by indium complexes. In the first
      method, a series of para-functionalized phenoxy-bridged dinuclear indium
      complexes [(NNO)InCl]2(MU-Cl)(MU-OPhR) (R = OMe (1), Me (2), H (3), Br (4), NO2
      (5)) were synthesized and fully characterized. The solution and solid state
      structures of these complexes reflect the electronic differences between these
      initiators. The polymerization rates correlate with the electron donating ability
      of the phenoxy initiators: the para-nitro substituted complex 5 is essentially
      inactive. However, the para-methoxy variant, while less active than the ethoxy
      bridged complex [(NNO)InCl]2(MU-Cl)(MU-OEt) (A), shows sufficient activity.
      Alternatively, aryl-capped PLAs were synthesized via immortal polymerization of
      PLA with A in the presence of a range of arylated chain transfer agents. Certain
      aromatic diols shut down polymerization by chelating one indium centre to form a
      stable metal complex. Immortal ROP was successful when using phenol, and 1,5
      naphthalenediol. These polymers were analysed and chain end fidelity was
      confirmed using 1H NMR spectroscopy, MALDI-TOF mass spectrometry, and UV-Vis
      spectroscopy. This study shed light on possible speciation when attempting to
      generate PLA-lignin copolymers.

PMID- 28488707
TI  - Emergent properties of extracellular vesicles: a holistic approach to decode the
      complexity of intercellular communication networks.
AB  - Shedding of nano-sized bilayered extracellular vesicles and extracellular vesicle
      mediated intercellular communication are evolutionarily conserved biological
      processes. Communication between cells and the environment is an essential
      process in living organisms and dysregulation of intercellular communication
      leads to various diseases. Thus, systematic studies on extracellular vesicles,
      also known as exosomes, microvesicles, and outer membrane vesicles, are critical
      for a deeper understanding of intercellular communication networks that are
      crucial for decoding the exact causes of various difficult-to-cure diseases.
      Recent progress in this emerging field reveals that extracellular vesicles are
      endogenous carriers of specific subsets of proteins, mRNAs, miRNAs, and other
      bioactive materials, as well as play diverse pathophysiological roles. However,
      certain issues regarding diverse subtypes and the complex pathophysiological
      roles of extracellular vesicles are not yet clearly elucidated. In this review,
      we first briefly introduce the complexity of extracellular vesicles in terms of
      their vesicular cargos and protein-protein interaction networks, their diverse
      subtypes, and multifaceted pathophysiological functions. Then, we introduce the
      limitation of reductionist approaches in understanding the complexity of
      extracellular vesicles. We finally suggest that molecular systems biology
      approaches based on the concept of emergent properties are essential for a
      comprehensive understanding of the complex pathophysiological functions of
      heterogeneous extracellular vesicles, either at the single vesicle level or at a
      systems level as a whole.

PMID- 28488709
TI  - Shear viscosity in hard-sphere and adhesive colloidal suspensions with reverse
      non-equilibrium molecular dynamics.
AB  - We employ the reverse non-equilibrium molecular dynamics method (RNEMD) of Muller
      Plathe [Phys. Rev. E, 1999, 59, 4894] to calculate the shear viscosity of
      colloidal suspensions within the stochastic rotation dynamics-molecular dynamics
      (SRD-MD) simulation method. We examine the influence of different coupling
      schemes in SRD-MD on the colloidal volume fraction phic dependent viscosity from
      the dilute limit up to phic = 0.3. Our results demonstrate that the RNEMD method
      is a robust and reliable method for calculating rheological properties of
      colloidal suspensions. To obtain quantitatively accurate results beyond the
      dilute regime, the hydrodynamic interactions between the effective fluid
      particles in the SRD and the MD colloidal particles must be carefully considered
      in the coupling scheme. We benchmark the method by comparing with the hard sphere
      suspension case, and then calculate relative viscosities for colloids with
      mutually attractive interactions. We show that the viscosity displays a sharp
      increase at the onset of aggregation of the colloidal particles with increasing
      volume fraction and attraction.

PMID- 28488710
TI  - Electric field directed formation of aligned conjugated polymer fibers.
AB  - Alternating current (AC) electric fields effectively align poly(3-alkylthiophene)
      (P3AT) fibers during a one-dimensional crystallization process. Structural,
      mechanical and electrical properties have been probed using microscopy, small
      angle neutron scattering (SANS), atomic force microscopy (AFM), X-ray diffraction
      (XRD), rheology, UV-Vis spectroscopy, and dielectric spectroscopy. Optimum
      frequency and amplitudes were identified for specific P3AT concentrations and for
      variable solvent quality. Optical microscopy along with SANS and XRD demonstrate
      alignment persists over both micrometer and nanometer length scales. Small
      amplitude oscillatory shear rheology also showed that the shear modulus increased
      for aligned fibers. The structural changes were correlated to improvements in
      electric conductivity as probed by dielectric spectroscopy. XRD experiments
      performed with variable sample orientations also showed that the P3HT pi-pi
      stacking direction was aligned parallel to the direction of the fiber axis.
      Electric field alignment was also possible for other alkyl-thiophene polymers and
      for polymers with simple backbone repeat units.

PMID- 28488712
TI  - Probing the interactions of organic molecules, nanomaterials, and microbes with
      solid surfaces using quartz crystal microbalances: methodology, advantages, and
      limitations.
AB  - Quartz crystal microbalances (QCMs) provide a new analytical opportunity and
      prospect to characterize many environmental processes at solid/liquid interfaces,
      thanks to their almost real-time measurement of physicochemical changes on their
      quartz sensor. This work reviews the applications of QCMs in probing the
      interactions of organic molecules, nanomaterials (NMs) and microbes with solid
      surfaces. These interfacial interactions are relevant to critical environmental
      processes such as biofilm formation, fate and transport of NMs, fouling in
      engineering systems and antifouling practices. The high sensitivity, real-time
      monitoring, and simultaneous frequency and dissipation measurements make QCM-D a
      unique technique that helps reveal the interaction mechanisms for the
      abovementioned processes (e.g., driving forces, affinity, kinetics, and the
      interplay between surface chemistry and solution chemistry). On the other hand,
      QCM measurement is nonselective and spatially-dependent. Thus, caution should be
      taken during data analysis and interpretation, and it is necessary to cross
      validate the results using complementary information from other techniques for
      more quantitative and accurate interpretation. This review summarizes the general
      methodologies for collecting and analyzing raw QCM data, as well as for
      evaluating the associated uncertainties. It serves to help researchers gain
      deeper insights into the fundamentals and applications of QCMs, and provides new
      perspectives on future research directions.

PMID- 28488714
TI  - A hierarchical NiO/NiMn-layered double hydroxide nanosheet array on Ni foam for
      high performance supercapacitors.
AB  - A hierarchical NiO/NiMn-LDH nanosheet array on Ni foam was prepared via a facile
      two-step approach and exhibited a high specific capacitance (937 F g-1 at 0.5 A g
      1) and good cycling stability (91% retention after 1000 cycles at 5 A g-1). The
      improved electrochemical performance is benefited from the synergistic properties
      of hierarchical NiO/LDH nanosheet composites on a conductive substrate.

PMID- 28488715
TI  - van der Waals interaction between a moving nano-cylinder and a liquid thin film.
AB  - We study the static and dynamic interaction between a horizontal cylindrical nano
      probe and a thin liquid film. The effects of the physical and geometrical
      parameters, with a special focus on the film thickness, the probe speed, and the
      distance between the probe and the free surface are analyzed. Deformation
      profiles have been computed numerically from a Reynolds lubrication equation,
      coupled to a modified Young-Laplace equation, which takes into account the
      probe/liquid and the liquid/substrate non-retarded van der Waals interactions. We
      have found that the film thickness and the probe speed have a significant effect
      on the threshold separation distance below which the jump-to-contact instability
      is triggered. These results encourage the use of horizontal cylindrical nano
      probes to scan thin liquid films, in order to determine either the physical or
      geometrical properties of the latter, through the measurement of interaction
      forces.

PMID- 28488717
TI  - Endothelial monolayer permeability under controlled oxygen tension.
AB  - Endothelial permeability has been extensively investigated in the context of
      pathologies such as cancer and also in studies of drug delivery from the
      circulation. Hypoxia is a critical regulator of endothelial cell (EC) behavior
      and affects the barrier function of endothelial linings, yet its role has been
      little studied. This paper reveals the effect of hypoxia on the permeability of
      an EC monolayer by cellular experiments using a microfluidic device and a
      conventional cell culture dish. Human umbilical vein endothelial cells (HUVECs)
      were seeded into one microfluidic channel, creating an EC monolayer on each
      vertical surface of a collagen gel confined to a central chamber. Oxygen tension
      was regulated to produce normoxic (21% O2) or hypoxic (3% O2) conditions by the
      supply of gas mixtures of oxygen, carbon dioxide, and nitrogen at predefined
      ratios into channels fabricated into the device. Permeability of the EC monolayer
      quantified by analyzing diffusion of fluorescence-labelled dextrans into the
      collagen gel increases with barrier function loss by 6 hour hypoxic exposure,
      showing 11-fold and 4-fold increases for 70 kDa and 10 kDa dextrans,
      respectively, on average. Consistent with this, subsequent immunofluorescent
      staining and separate western blot analysis of HUVECs on a culture dish
      demonstrate loose cell-cell adhesion resulting from internalization of VE
      cadherin under hypoxia. Thus, hypoxic stress increases endothelial permeability
      by altering cell-cell junction integrity.

PMID- 28488718
TI  - Nonspherical armoured bubble vibration.
AB  - In this paper, we study the dynamics of cylindrical armoured bubbles excited by
      mechanical vibrations. A step by step transition from cylindrical to spherical
      shape is reported as the intensity of the vibration is increased, leading to a
      reduction of the bubble surface and a dissemination of the excess particles. We
      demonstrate through energy balance that nonspherical armoured bubbles constitute
      a metastable state. The vibration instills the activation energy necessary for
      the bubble to return to its least energetic stable state: a spherical armoured
      bubble. At this point, particle desorption can only be achieved through higher
      amplitude of excitation required to overcome capillary retention forces.
      Nonspherical armoured bubbles open perspectives for tailored localized particle
      dissemination with limited excitation power.

PMID- 28488719
TI  - Non-edible parts of Solanum stramoniifolium Jacq. - a new potent source of
      bioactive extracts rich in phenolic compounds for functional foods.
AB  - Extracts prepared from leaves, roots, and stems of Solanum stramoniifolium Jacq.
      (Solanaceae) in 80% ethanol have been tested for their in vitro antioxidant, anti
      inflammatory, antimicrobial, and cytotoxic activities with an aim to find new
      sources of substances for functional foods and food additives. The root extract
      revealed the highest antioxidant activity in all assays exceeding the trolox
      capacity, and was the only extract that inhibited nitric oxide production in
      mouse macrophage cells, showing also the capacity to suppress the growth of all
      tested human tumor cell lines (MCF-7, NCI-H460, HeLa and HepG2). The leaf extract
      showed the strongest antimicrobial activity inhibiting all tested clinical
      isolates. To the author's best knowledge it was the first time that all
      individual parts of this plant were tested for biological activity together with
      the phenolic compound characterization.

PMID- 28488720
TI  - A dynamic strategy for wavelength sensing using the diffracted orders of a
      grating.
AB  - We propose a strategy for real time multicolour detection of light emitting
      particles under flow conditions, using the diffracted orders of a grating. The
      method relies on the fact that the spatial (angular/linear) separation between
      the orders of a diffraction grating is a wavelength dependent quantity. Thus, the
      difference in arrival times at a fixed detector for neighbouring orders produced
      by a moving, light-emitting particle can be used as a wavelength sensing
      mechanism. We demonstrate this functionality using a prototype PDMS microfluidic
      device that incorporates a focusing transmission grating. A key attribute of this
      approach is that it requires only a single sensitive detector, such as a
      photomultiplier tube, in contrast to many conventional approaches which require
      multiple sensitive detectors or a detector array.

PMID- 28488721
TI  - Fluorinated cyclometalated iridium(iii) complexes as mitochondria-targeted
      theranostic anticancer agents.
AB  - Six cyclometalated iridium(iii) complexes bearing different numbers of fluorine
      atoms were synthesized. These complexes demonstrated much better anti
      proliferation activities towards five tumour cell lines than the widely used
      clinical chemotherapeutic agent cisplatin. Moreover, the anti-proliferation
      activities were correlated to the number of substituted fluorine atoms.
      Colocalization and inductively coupled plasma-mass spectrometry (ICP-MS)
      indicated that this series of complexes could penetrate cell membranes rapidly
      and preferentially target mitochondria. Manifesting high selectivity between
      tumour cells and normal cells and remarkable sensitivity to a cisplatin-resistant
      cell line (A549R), complex Ir6 was successfully developed as a novel anticancer
      agent (with IC50 values of 0.5 +/- 0.1 MUM for HeLa, 1.1 +/- 0.2 MUM for HepG2,
      1.5 +/- 0.3 MUM for BEL-7402, 0.8 +/- 0.1 MUM for A549, and 0.7 +/- 0.2 MUM for
      A549R cell lines). Further mechanism studies including mitochondrial membrane
      potential depolarization and caspase 3/7 activation revealed that Ir6 induced
      apoptosis via mitochondrial pathways. These results demonstrated that complex Ir6
      might be a promising candidate as a mitochondria-targeted theranostic anticancer
      agent.

PMID- 28488723
TI  - Experimental observation of Shapiro-steps in colloidal monolayers driven across
      time-dependent substrate potentials.
AB  - We experimentally study the motion of a colloidal monolayer which is driven
      across a commensurate substrate potential whose amplitude is periodically
      modulated in time. In addition to a significant reduction of the static friction
      force compared to an unmodulated substrate, we observe a Shapiro step structure
      in the force dependence of the mean particle velocity which is explained by the
      dynamical mode locking between the particle motion and the substrate modulation.
      In this regime, the entire crystal moves in a stick-slip fashion similar to what
      is observed when a single point contact is driven across a periodic surface.
      Contrary to numerical simulations, where typically a large number of Shapiro
      steps is found, only a single step is observed in our experiments. This is
      explained by the formation of kinks which weaken the synchronization between
      adjacent particles.

PMID- 28488724
TI  - Complex effect of zinc oxide nanoparticles on cadmium chloride-induced
      hepatotoxicity in mice: protective role of metallothionein.
AB  - The wide range of applications of ZnO nanoparticles (nano ZnO) in commercial
      products and the ubiquitous cadmium (Cd) contamination in the natural environment
      increase the chance of co-existence of nano ZnO with Cd in the surroundings. To
      investigate the effects of nano ZnO on CdCl2-induced hepatotoxicity in mice, the
      histopathologic changes, metallothionein expression, oxidative stress responses
      and serum biochemical parameters were determined after oral administration of
      bulk or nano ZnO and/or CdCl2 for seven consecutive days. Bulk or nano ZnO had
      low toxicity in mice. In contrast, CdCl2 led to significant hepatic oxidative
      damage, as indicated by hepatic histopathological abnormalities and dysfunction.
      Bulk and nano ZnO had nearly identical influences on the hepatotoxicity of CdCl2
      in mice. Although co-administration of bulk or nano ZnO with CdCl2 had a positive
      cooperative effect on the hepatic uptake of Cd and Zn, both bulk and nano ZnO
      significantly attenuated CdCl2-caused hepatic damage via the reduction of
      oxidative stress. The increase in metallothionein synthesis and the reduction of
      Cd-induced perturbation of Zn2+ homeostasis after co-administration of bulk or
      nano ZnO with CdCl2 play two important roles in the protective effect of bulk or
      nano ZnO on CdCl2-caused hepatic oxidative damage.

PMID- 28488725
TI  - A rare case of Marine-Lenhart syndrome with unilateral endocrine orbitopathy and
      Hurthle cell carcinoma.

PMID- 28488726
TI  - Prediction of renal cortical defect and scar using neutrophil-to-lymphocyte ratio
      in children with febrile urinary tract infection.
AB  - AIM: This study is aimed to evaluate the predictive value of the neutrophil-to
      lymphocyte ratio (NLR) for cortical defect on initial and follow-up Tc-99m
      dimercaptosuccinic acid (DMSA) scan in children with the first febrile urinary
      tract infection (UTI). METHODS: We retrospectively enrolled 179 children with the
      first febrile UTI who underwent DMSA scan and laboratory tests. In patients with
      abnormal DMSA scan findings, follow-up DMSA scan was performed at least 6 months
      after the initial scan. All DMSA scans were classified as negative and positive
      cortical defects. Multiple logistic regression analyses were performed to
      identify the risk factors for cortical defect on initial and follow-up DMSA scan.
      RESULTS: Cortical defects on initial DMSA scan were noted in 133 patients.
      Vesicoureteral reflux (VUR), white blood cell count, absolute neutrophil count,
      NLR, and serum C-reactive protein level were independent predictive factors for
      positive cortical defect on initial DMSA scan (p < 0.050). On follow-up DMSA
      scan, 24 of the 133 patients showed persistent cortical defects, and only VUR was
      significantly associated with persistent cortical defect (p = 0.002). In 84
      patients who showed cortical defect on initial scan and absence of VUR, only NLR
      was significantly associated with persistent cortical defect on follow-up scan (p
      = 0.025). CONCLUSION: NLR was significantly associated with persistent cortical
      defect on follow-up DMSA scan in patients without VUR, as well as positive
      cortical defect on initial scan.

PMID- 28488727
TI  - Differences in sodium fluoride-18 uptake in the normal skeleton depending on the
      location and characteristics of the bone.
AB  - AIM: The aim of this study was to evaluate the normal distribution of sodium
      fluoride-18 (NaF-18) and to clarify the differences in uptake according to
      location and the type of the bone using positron emission tomography (PET) /
      computed tomography (CT). METHODS: We retrospectively reviewed NaF-18 PET/CT
      images from 30 patients with hip joint disorders. PET/CT scans were performed 40
      min after injection of approximately 185 MBq of NaF-18. To evaluate the
      relationship between the distribution of NaF-18 uptake and bone density, we
      compared the maximum standardised uptake values (SUVmax) on PET and the
      Hounsfield Units (HUs) on CT of the lumbar vertebra, ilium, and proximal and
      distal femurs. Regions of interests were defined both outside and inside the
      cortical bone to measure whole bone and cancellous bone only, respectively.
      RESULTS: The distribution of NaF-18 differed according to the skeletal site. The
      lumbar vertebra showed the highest SUVmax for both whole bone and cancellous
      bone, followed by the ilium, proximal femur, and distal femur. The bones differed
      significantly in SUVmax. The distal femur showed the highest HU, followed by the
      proximal femur, ilium, and vertebra. Profile curve analyses demonstrated that the
      cancellous bones showed higher SUVmax and lower HU than the cortical bones.
      CONCLUSIONS: Our results demonstrate the difference in NaF-18 uptake between
      cancellous and cortical bones, which may explain differences in uptake by
      location. NaF-18 uptake does not appear to be strongly correlated with bone
      density, but rather with bone turnover and blood flow.

PMID- 28488728
TI  - Fatty acid amide hydrolase (FAAH) regulates hypercapnia/ischemia-induced
      increases in n-acylethanolamines in mouse brain.
AB  - N-acylethanolamines (NAEs) are endogenous lipid ligands for several receptors
      including cannabinoid receptors and peroxisome proliferator-activated receptor
      alpha (PPAR-alpha), which regulate numerous physiological functions. Fatty acid
      amide hydrolase (FAAH) is largely responsible for the degradation of NAEs.
      However, at high concentrations of ethanolamines and unesterified fatty acids,
      FAAH can also catalyze the reverse reaction, producing NAEs. Several brain
      insults such as ischemia and hypoxia increase brain unesterified fatty acids.
      Because FAAH can catalyze the synthesis of NAE, we aimed to test whether FAAH was
      necessary for CO2 -induced hypercapnia/ischemia increases in NAE. To test this,
      we examined levels of NAEs, 1- and 2-arachidonoylglycerols as well as their
      corresponding fatty acid precursors in wild-type and mice lacking FAAH (FAAH-KO)
      with three Kill methods: (i) head-focused, high-energy microwave irradiation
      (microwave), (ii) 5 min CO2 followed by microwave irradiation (CO2 + microwave),
      and (iii) 5 min CO2 only (CO2 ). Both CO2 -induced groups increased, to a similar
      extent, brain levels of unesterified oleic, arachidonic, and docosahexaenoic acid
      and 1- and 2-arachidonoylglycerols compared to the microwave group in both wild
      type and FAAH-KO mice. Oleoylethanolamide (OEA), arachidonoylethanolamide (AEA),
      and docosahexaenoylethanolamide (DHEA) levels were about 8-, 7-, and 2.5-fold
      higher, respectively, in the FAAH-KO mice compared with the wild-type mice.
      Interestingly, the concentrations of OEA, AEA, and DHEA increased 2.5- to 4-fold
      in response to both CO2 -induced groups in wild-type mice, but DHEA increased
      only in the CO2 group in FAAH-KO mice. Our study demonstrates that FAAH is
      necessary for CO2 - induced increases in OEA and AEA but not DHEA. Targeting
      brain FAAH could impair the production of NAEs in response to brain injuries.

PMID- 28488729
TI  - Randomized clinical trial of biodegradeable intraluminal sheath to prevent
      anastomotic leak after stapled colorectal anastomosis.
AB  - BACKGROUND: Anastomotic leakage is a potential major complication after
      colorectal surgery. The C-seal was developed to help reduce the clinical leakage
      rate. It is an intraluminal sheath that is stapled proximal to a colorectal
      anastomosis, covering it intraluminally and thus preventing intestinal leakage in
      case of anastomotic dehiscence. The C-seal trial was initiated to evaluate the
      efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal
      anastomoses. METHODS: This RCT was performed in 41 hospitals in the Netherlands,
      Germany, France, Hungary and Spain. Patients undergoing elective surgery with a
      stapled colorectal anastomosis less than 15 cm from the anal verge were eligible.
      Included patients were randomized to the C-seal and control groups, stratified
      for centre, anastomotic height and intention to create a defunctioning stoma.
      Primary outcome was anastomotic leakage requiring invasive treatment. RESULTS:
      Between December 2011 and December 2013, 402 patients were included in the trial,
      202 in the C-seal group and 200 in the control group. Anastomotic leakage was
      diagnosed in 31 patients (7.7 per cent), with a 10.4 per cent leak rate in the C
      seal group and 5.0 per cent in the control group (P = 0.060). Male sex showed a
      trend towards a higher leak rate (P = 0.055). Construction of a defunctioning
      stoma led to a lower leakage rate, although this was not significant (P = 0.095).
      CONCLUSION: C-seal application in stapled colorectal anastomoses does not reduce
      anastomotic leakage. Registration number: NTR3080
      (http://www.trialregister.nl/trialreg/index.asp).

PMID- 28488730
TI  - Octreotide-Associated Neutropenia.
AB  - Drug-induced neutropenia and agranulocytosis are rare adverse events but can be
      fatal. Neutropenia can be induced by a myriad of drugs from almost every
      pharmacologic class. Octreotide is a somatostatin analog that has been used to
      treat variceal bleeding, acromegaly, and severe diarrhea associated with
      metastatic tumors, and to reduce symptoms in the setting of malignant bowel
      obstruction and pseudoobstruction. The most common adverse effects associated
      with octreotide include pain at the injection site and gastrointestinal effects
      such as loose stools, cramping, and nausea; neutropenia is not currently listed
      as an adverse effect of the drug. We describe the case of an 87-year-old man who
      developed neutropenia immediately after administration of three doses of
      subcutaneous octreotide. He presented to the hospital with a history of
      constipation and straining for 3 days. He was admitted, and laxatives,
      suppositories, and enemas were administered over the next 3 days to induce a
      bowel movement; however, they were ineffective. Bowel obstruction secondary to a
      mass was confirmed by computed tomography; the mass was eventually diagnosed as
      colon cancer. Octreotide 100 ug subcutaneously every 8 hours was started for the
      obstruction on the evening of hospital day 4. After the patient had received 3
      doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 *
      103 /mm3 (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 * 103 /mm3 ) on
      admission to 1.6 * 103 /mm3 (neutrophils 62%, ANC 0.99 * 103 /mm3 ) on day 5.
      Given the temporal relationship of octreotide and neutropenia as well as the lack
      of a reasonable alternative cause, it was suspected that octreotide was the most
      likely culprit of the patient's neutropenia. Octreotide was subsequently
      discontinued, and his WBC increased to 4.9 * 103 /mm3 (neutrophils 66.3%, ANC 3.2
      * 103 /mm3 ) the next day. The remainder of the patient's hospitalization was not
      significant for any further hematologic abnormalities. His WBC and ANC (WBC 6.7 *
      103 /mm3 , neutrophils 83.2%, ANC 5.6 * 103 /mm3 ) remained stable 30 days after
      the incident. Use of the Naranjo Adverse Drug Reaction Probability Scale
      indicated a probable relationship (score of 5) between the patient's development
      of neutropenia and octreotide therapy. To our knowledge, this report highlights
      the first case of octreotide-associated neutropenia. Although the frequency of
      drug-induced neutropenia remains rare outside of cytotoxic chemotherapy, the
      importance of recognizing this adverse effect cannot be understated given the
      mortality risks for neutropenic patients.

PMID- 28488731
TI  - Development of a rectal sexually transmitted infection (STI) Model in Rhesus
      macaques using Chlamydia trachomatis serovars E and L2.
AB  - BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV
      transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were
      exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C.
      trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or
      CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly
      blood and rectal secretion/lavage samples were collected for cytokine analyzes
      and/or epithelial sloughing, occult, and overt blood determinations. RESULTS:
      Chlamydial infections were successfully established in each animal, with varying
      degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively
      infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also
      significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This
      study demonstrates successful rectal infection of rhesus macaques with CT-E and
      CT-L2 and describes measures of assessing rectal inflammation and pathology.
      Different infection strategies yield varying inflammatory and pathologic
      outcomes, providing well-described models for future SIV/SHIV susceptibility
      studies.

PMID- 28488732
TI  - Involvement of the Warburg effect in non-tumor diseases processes.
AB  - Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation
      to aerobic glycolysis, is extensively found in various cancers. Interestingly,
      increasing researchers show that Warburg effect plays a crucial role in non-tumor
      diseases. For instance, inhibition of Warburg effect can alleviate pulmonary
      vascular remodeling in the process of pulmonary hypertension (PH). Interference
      of Warburg effect improves mitochondrial function and cardiac function in the
      process of cardiac hypertrophy and heart failure. Additionally, the Warburg
      effect induces vascular smooth muscle cell proliferation and contributes to
      atherosclerosis. Warburg effect may also involve in axonal damage and neuronal
      death, which are related with multiple sclerosis. Furthermore, Warburg effect
      significantly promotes cell proliferation and cyst expansion in polycystic kidney
      disease (PKD). Besides, Warburg effect relieves amyloid beta-mediated cell death
      in Alzheimer's disease. And Warburg effect also improves the mycobacterium
      tuberculosis infection. Finally, we also introduce some glycolytic agonists. This
      review focuses on the newest researches about the role of Warburg effect in non
      tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF),
      failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases,
      multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential
      therapeutic target for those non-tumor diseases.

PMID- 28488733
TI  - Surgical resection for Bismuth type IV perihilar cholangiocarcinoma.
AB  - BACKGROUND: Bismuth type IV perihilar cholangiocarcinoma has traditionally been
      categorized as unresectable disease. The aim of this study was to review
      experience with a resection-based strategy in patients who have type IV perihilar
      cholangiocarcinoma. METHODS: Medical records of consecutive patients with a
      diagnosis of type IV perihilar cholangiocarcinoma between 2006 and 2015 were
      reviewed retrospectively. Primary outcomes assessed were surgical results and
      long-term survival. RESULTS: Of the 332 patients with type IV tumour, 216 (65.1
      per cent) underwent resection. Left hepatic trisectionectomy was the most common
      procedure (112 patients). Combined vascular resection was performed in 131
      patients. Median duration of operation was 607 (range 356-1045) min, and blood
      loss was 1357 (209-10 349) ml. Complications of Clavien-Dindo grade III or more
      developed in 90 patients (41.7 per cent) and four (1.9 per cent) died from
      complications within 90 days. Survival rates were better for the 216 patients
      whose tumours were resected than for the 116 patients with unresected tumours
      (32.8 versus 1.5 per cent at 5 years; P < 0.001). Patients with pN0 M0 disease
      after resection had a favourable 5-year survival rate of 53 per cent.
      Percutaneous transhepatic biliary drainage, blood transfusion, lymph node
      metastasis and distant metastasis were identified as independent negative
      prognostic factors for survival. CONCLUSION: Although resection for type IV
      tumour is technically demanding with high morbidity, it can be performed with low
      mortality and offers better survival probability in selected patients.

PMID- 28488734
TI  - Body Size and the Risk of Primary Hyperparathyroidism in Women: A Cohort Study.
AB  - Greater body weight and fat mass have been associated with higher serum
      parathyroid hormone levels and a higher prevalence of primary hyperparathyroidism
      (P-HPTH) in women. However, prospective studies to evaluate whether greater body
      size associates with a higher incidence of developing P-HPTH have not been
      reported. We investigated whether greater body size was independently associated
      with a higher risk for developing P-HPTH in women. We conducted a prospective
      cohort study of 85,013 female participants in the Nurses' Health Study I followed
      for up to 26 years. Body size was measured via multiple metrics: weight, body
      mass index (BMI), and waist circumference (WC). Weight and BMI were assessed
      every 2 years from 1986 to 2012, and WC was assessed in 1986, 1996, and 2000.
      Detailed dietary and demographic exposures were quantified via validated biennial
      questionnaires. Incident cases of P-HPTH were confirmed by individual medical
      record review. Cox proportional hazards models were used to evaluate whether WC,
      weight, and BMI were independent risk factors for developing P-HPTH. Models were
      adjusted for demographic variables, comorbidities, medications, intakes of
      calcium and vitamin D, and exposure to ultraviolet light. We confirmed 491
      incident cases of P-HPTH during 2,128,068 person-years of follow-up. The
      multivariable-adjusted relative risks for incident P-HPTH increased across
      quartiles of WC: Q1, ref; Q2, 1.34 (0.97, 1.86); Q3, 1.70 (1.24, 2.31); Q4, 2.27
      (1.63, 3.18); p trend < 0.001. Similarly, the multivariable-adjusted risks for
      incident P-HPTH increased across quartiles of weight: Q1, ref; Q2, 1.23 (0.92,
      1.65); Q3, 1.63 (1.24, 2.14); Q4, 1.65 (1.24, 2.19); p trend < 0.001. A similar
      but statistically non-significant trend was observed across quartiles of BMI (p
      trend = 0.07). In summary, body size may be an independent and modifiable risk
      factor for developing P-HPTH in women. (c) 2017 American Society for Bone and
      Mineral Research.

PMID- 28488735
TI  - TERMITE: An R script for fast reduction of laser ablation inductively coupled
      plasma mass spectrometry data and its application to trace element measurements.
AB  - RATIONALE: High spatial resolution Laser Ablation Inductively Coupled Plasma Mass
      Spectrometry (LA-ICPMS) determination of trace element concentrations is of great
      interest for geological and environmental studies. Data reduction is a very
      important aspect of LA-ICP-MS, and several commercial programs for handling LA
      ICPMS trace element data are available. Each of these software packages has its
      specific advantages and disadvantages. METHODS: Here we present TERMITE, an R
      script for the reduction of LA-ICPMS data, which can reduce both spot and line
      scan measurements. Several parameters can be adjusted by the user, who does not
      necessarily need prior knowledge in R. Currently, ten reference materials with
      different matrices for calibration of LA-ICPMS data are implemented, and
      additional reference materials can be added by the user. TERMITE also provides an
      optional outlier test, and the results are provided graphically (as a pdf file)
      as well as numerically (as a csv file). RESULTS: As an example, we apply TERMITE
      to a speleothem sample and compare the results with those obtained using the
      commercial software GLITTER. The two programs give similar results. TERMITE is
      particularly useful for samples that are homogeneous with respect to their major
      element composition (in particular for the element used as an internal standard)
      and when many measurements are performed using the same analytical parameters. In
      this case, data evaluation using TERMITE is much faster than with all other
      available software, and the concentrations of more than 100 single spot
      measurements can be calculated in less than a minute. CONCLUSIONS: TERMITE is an
      open-source software for the reduction of LA-ICPMS data, which is particularly
      useful for the fast, reproducible evaluation of large datasets of samples that
      are homogeneous with respect to their major element composition. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28488736
TI  - Inhibition of mTOR pathway decreases the expression of pre-meiotic and meiotic
      markers throughout postnatal development and in adult testes in mice.
AB  - Rapamycin (mTOR inhibitor) has been reported to have negative effect on human
      male gonadal function. Previously, we showed that mTOR signalling molecules are
      expressed during early spermatogenesis in mice. The objective of this study was
      to investigate the role of mTOR signalling in meiosis both during the first wave
      of spermatogenesis and also during adult spermatogenesis. Day 5 post-partum mice
      were administered rapamycin and retinoic acid (RA; a Stra8 activator), and
      expression of p-p70S6K and Stra8 proteins was evaluated. p-p70S6K and Stra8
      protein expressions decreased in post-natal testes after rapamycin treatment.
      Stra8 protein expression increased after RA and rapamycin+RA administrations in
      post-natal testes. In adult mice, rapamycin was administrated for 1 or 4 weeks.
      Morphological analysis for testicular damage and TUNEL assay was performed. After
      rapamycin administration, germ cell loss increased in adult testes.
      Ultrastructural analysis revealed disorganised testicular morphology and
      vacuolisation. The number of apoptotic germ cells increased after 4 weeks
      rapamycin administration. Stra8 and Dmc1 expressions decreased in 4 weeks
      rapamycin group, whereas Sycp3 and VASA expression did not change. Our findings
      suggest that mTOR pathway has an important role in meiotic progress of male germ
      cells both during first wave of spermatogenesis and in adult mice.

PMID- 28488737
TI  - Angiotensin II signalling kicks out p27Kip1 : casein kinase 2 augmentation of Cav
      1.2 L-type Ca2+ channel activity in immature ventricular cardiomyocytes.

PMID- 28488738
TI  - Comparison of three different extenders on Murrah buffaloes (Bubalus bubalis)
      semen freezability.
AB  - The use of frozen semen for artificial insemination is the main approach utilised
      for the genetic improvement of most domesticated species. The advantages include
      lower transportation costs, continuous availability of semen, fewer occurrences
      of sexually transmitted diseases and the incorporation of desirable genes in a
      relatively short amount of time. Nevertheless, the use of frozen semen in buffalo
      herds remains limited due to the loss of sperm quality when buffalo semen is
      frozen. So, the goal of this study was to evaluate the pre- and post
      cryopreservation quality of buffalo semen diluted in three distinct freezing
      media: Tris-egg yolk, Botu-bov(r) (BB) and ACP-111(r). Thirty-two ejaculates from
      four bulls were analysed in terms of kinetics, morphology and sperm viability by
      epifluorescence microscope. Thawed samples were also evaluated for capacitation
      like damage, DNA fragmentation and plasma and acrosomal membrane integrity using
      flow cytometry. The Tris-egg yolk and BB(r) extenders yielded better results than
      the ACP-111(r) extender for kinetics parameter (total motility, progressive
      motility and percentage of rapid cells). However, semen samples were similar for
      parameters evaluated by flow cytometry. Taken together, the data indicate that in
      comparison with Tris-egg yolk and BB extender, ACP-111(r) can also be used as an
      extender for buffalo semen cryopreservation.

PMID- 28488739
TI  - Reducing contamination parameters for clumped isotope analysis: The effect of
      lowering PorapakTM Q trap temperature to below -50 degrees C.
AB  - RATIONALE: Carbonate clumped isotope thermometry examines the thermodynamic
      preference of 13 C-18 O bonds to form within the carbonate crystal lattice. The
      13 C18 O16 O isotopologue in analyte CO2 has a natural abundance of 44.4 ppm
      necessitating stringent purification procedures to remove contaminant molecules
      that may produce significant isobaric effects within range of the mass 47
      isotopologue. Strict purifications of analyte CO2 are thus required as well as
      reliable contamination indicators. METHODS: CO2 purification was carried out by
      vacuum cryogenic purification through a static trap packed with PorapakTM Q
      (PPQ). The correlation between mass excesses on m/z 47, 48 and 49 in CO2 produced
      by acid digestion of 12 natural samples was measured by isotope ratio mass
      spectrometry (IRMS). CO2 from two contaminated carbonate samples was then
      purified at PPQ trap temperatures between -25 and -65 degrees C and measured by
      IRMS to determine changes in mass excesses on m/z 47, 48 and 49. Finally
      carbonate standards, Carrara marble (CM) and ETH3, were purified at PPQ trap
      temperatures of -35 and -60 degrees C to identify isotopic fractionation
      associated with lowering trap temperature. RESULTS: The correlation between mass
      excesses on m/z 47, 48 and 49 is determined to be sample dependent. Lowering the
      PPQ trap temperature to -60 degrees C has a 78% success rate in decreasing
      Delta48offset , a measure of sample contamination, to within an acceptable range
      (<1.5 0/00). Lowering the PPQ temperature in purification of CM and ETH3 is
      associated with decreases in the delta13 C and delta18 O values as a result of
      isotopic fractionation. We demonstrate that we can correct for fractionation at a
      trap temperature of -60 degrees C. CONCLUSIONS: Lowering the temperature of the
      Porapak Q trap to -60 degrees C results in improved sample cleaning. It is
      possible to correct for fractionation in delta13 C and delta18 O values at lower
      PPQ trap temperatures using identically prepared standards. This result has
      important connotations for laboratories using similar sample preparation methods.

PMID- 28488740
TI  - Ethanol-induced mitophagy in rat Sertoli cells: Implications for male fertility.
AB  - Autophagy is a pro-survival mechanism involving lysosomal degradation of damaged
      cellular components following multiple forms of cellular stress. There is
      currently a lack of literature on the mechanism, and specifically on mitophagy
      (selective autophagy of damaged pro-apoptotic mitochondria) in Sertoli cells
      (SCs). Against such a background, the authors induced mitophagy in SCs of adult
      male rats using a single injection of ethanol (5 g/kg) and observed mitophagy in
      the SCs via transmission electron microscopy 24 hr later. In addition, we briefly
      discussed the possible clinical implications of enhanced autophagy and mitophagy
      in stressed SCs in our model and in other models of acute stress (e.g., heat and
      transplantation stress). Further studies on SC autophagy are required, as a full
      understanding of the molecular mechanisms controlling autophagy in stressed SCs
      may have therapeutic implications for infertility treatment.

PMID- 28488741
TI  - Cancer screening is not only about numbers.
AB  - In the cancer screening debate, arguments for and against screening are often
      based on statistics, whereas for individuals personal, non-statistical factors
      are at least as important when deciding whether to participate in screening.
      Health care professionals have a responsibility in helping individuals navigate
      in this complex field by identifying and clarifying the individuals' beliefs,
      fears and preferences while being aware of their own. Moreover, researchers
      should explore beliefs and motives that matter for individuals and not only
      report numbers that can be interpreted in different ways.

PMID- 28488742
TI  - Feminization of the fat distribution pattern of children and adolescents in a
      recent German population.
AB  - OBJECTIVES: During the early 1990s, the economic and political situation in
      eastern Germany changed overnight. Here, we use the rare chance of an experiment
      like setting in humans and aim to test whether the rapid change of environmental
      conditions in eastern Germany in the 1990s led to a change in the sex-specific
      fat distribution pattern, an endocrine-influenced phenotypic marker. METHODS:
      Based on a cross-sectional data set of 6- to 18-year-old girls and boys measured
      between 1982-1991 and 1997-2012, we calculated a skinfold ratio of triceps to
      subscapular and percentage of body fat. Using linear regressions, we tested for
      differences in percentage of body fat and skinfold ratio between these two time
      periods. RESULTS: We found that the percentage of body fat increased in boys and
      girls, and they accumulated relatively more fat on extremities than on the trunk
      in all BMI groups measured after 1997 as compared to those measured between 1982
      and 1991. CONCLUSIONS: Concurrent with drastic and rapid changes of environmental
      conditions, the body fat distribution of children and adolescents changed to a
      more feminized pattern during the early 1990s in an East German population. The
      changes in this endocrinologically mediated pattern might be associated with the
      increased exposure of individuals to endocrine-disrupting chemicals which are
      known to influence the endocrine, reproductive, and immune systems in animals and
      humans.

PMID- 28488743
TI  - Photoisomerization of Bis(tridentate) 2,6-Bis(1H-pyrazol-1-yl)pyridine Ligands
      Exhibiting a Multi-anthracene Skeleton.
AB  - A novel molecular design is described where two peripheral moieties made of 2,6
      bis(1H-pyrazol-1-yl)pyridine are linked through multi-1,8-diethynylanthracene
      moieties. The optimized synthesis of the three isostructural analogues 1 a, 1 b,
      and 1 c, containing the anthraquinone, anthracene, and 10-methoxyanthracene
      units, respectively, is reported. The resulting spatial face-to-face arrangement
      of the peripheral anthracene rings enables to trigger the intramolecular [4+4]
      photocycloaddition affording the isomers P1 b and P1 c, which can be thermally
      cleaved back to the original anthracene derivatives 1 b and 1 c, respectively.
      Single-crystal X-ray diffraction studies confirm the expected molecular
      structures of compounds 1 a-1 c as well as of their corresponding isomers P1 b
      and P1 c. The spectral, optical, and electrochemical properties of all
      synthesized compounds are investigated and discussed.

PMID- 28488744
TI  - Membrane vesicle secretion and prophage induction in multidrug-resistant
      Stenotrophomonas maltophilia in response to ciprofloxacin stress.
AB  - Several bacterial species produce membrane vesicles (MVs) in response to
      antibiotic stress. However, the biogenesis and role of MVs in bacterial
      antibiotic resistance mechanisms have remained unclear. Here, we studied the
      effect of the fluoroquinolone ciprofloxacin on MV secretion by Stenotrophomonas
      maltophilia using a combination of electron microscopy and proteomic approaches.
      We found that in addition to the classical outer membrane vesicles (OMV),
      ciprofloxacin-stimulated cultures produced larger vesicles containing both outer
      and inner membranes termed outer-inner membrane vesicles (OIMV), and that such
      MVs are enriched with cytosolic proteins. Remarkably, OIMV were found to be
      decorated with filamentous structures identified as fimbriae. In addition,
      ciprofloxacin stress leads to the release of bacteriophages and phage tail-like
      particles. Prophage induction by ciprofloxacin has been linked to pathogenesis
      and horizontal gene transfer in several bacterial species. Together, our findings
      show that ciprofloxacin treatment of S. maltophilia leads to the secretion of a
      heterogeneous pool of MVs and the induction of prophages that are potentially
      involved in adverse side-effects during antibiotic treatment.

PMID- 28488745
TI  - The 2-week wait and other initiatives to improve cancer diagnosis: Has it altered
      survival? The answer is unclear-the evidence is too weak.
AB  - The UK is one of the lowest ranked high-income countries for cancer survival.
      Later stage at diagnosis is a significant contributor to reduced survival.
      Several strategies have been introduced to reduce delays in an effort to diagnose
      cancer earlier. This commentary summarises the evidence and impact of these
      initiatives.

PMID- 28488747
TI  - Ultra-performance liquid chromatography/multiple reaction monitoring mass
      spectrometry quantification of trastuzumab in human serum by selective monitoring
      of a specific peptide marker from the antibody complementarity-determining
      regions.
AB  - RATIONALE: Because of the large molecular weight, the structural complexity and
      the similarity with endogenous immunoglobulins present in high concentrations, in
      vivo quantitative studies with therapeutic monoclonal antibodies are particularly
      challenging. In this work, an UPLC/MRM MS-based methodology is described for the
      quantification of trastuzumab in human serum by monitoring a novel specific
      peptide marker located within its heavy chain Complementarity-Determining Region
      (CDR). METHODS: For maximum sensitivity and selectivity, specific transitions of
      this diagnostic proteotypic peptide were optimized and monitored at m/z 364.1 ->
      437.3 (quantitation ion) and m/z 364.1 -> 358.0 (confirmation ion). As a proof-of
      concept, the methodology was applied to the determination of trastuzumab in human
      serum over a clinically relevant range from 0.02 to 200 MUg/mL. The methodology
      has been evaluated in terms of specificity, linearity, accuracy, precision,
      detection and quantitation limits. RESULTS: An excellent linear response has been
      obtained in the range from 0.036 to 3.6 fmol/MUL for the standard peptide and
      from 0.03 to 285 fmol/MUL for the trastuzumab in human serum with typical R2
      values of 0.99. The limit of detection (LOD) and limit of quantification (LOQ)
      are 0.005 fmol/MUL and 0.05 fmol/MUL, respectively, with mean bias and RSD values
      of 18% and 1%, respectively, for quality control samples. CONCLUSIONS: The
      strategy used to set up the UPLC/MRM MS methodology based on monitoring specific
      peptide markers within CDRs can be potentially applied to the detection and
      quantification of other humanized or human mAbs in biological fluids. Copyright
      (c) 2017 John Wiley & Sons, Ltd.

PMID- 28488748
TI  - Formation of Double-Shelled Zinc-Cobalt Sulfide Dodecahedral Cages from
      Bimetallic Zeolitic Imidazolate Frameworks for Hybrid Supercapacitors.
AB  - Complex metal-organic frameworks used as precursors allow design and construction
      of various nanostructured functional materials which might not be accessible by
      other methods. Here, we develop a sequential chemical etching and sulfurization
      strategy to prepare well-defined double-shelled zinc-cobalt sulfide (Zn-Co-S)
      rhombic dodecahedral cages (RDCs). Yolk-shelled zinc/cobalt-based zeolitic
      imidazolate framework (Zn/Co-ZIF) RDCs are first synthesized by a controlled
      chemical etching process, followed by a hydrothermal sulfurization reaction to
      prepare double-shelled Zn-Co-S RDCs. Moreover, the strategy reported in this work
      enables easy control of the Zn/Co molar ratio in the obtained double-shelled Zn
      Co-S RDCs. Owing to the structural and compositional benefits, the obtained
      double-shelled Zn-Co-S RDCs exhibit enhanced performance with high specific
      capacitance (1266 F g-1 at 1 A g-1 ), good rate capability and long-term cycling
      stability (91 % retention over 10,000 cycles) as a battery-type electrode
      material for hybrid supercapacitors.

PMID- 28488749
TI  - How are we assessing the safety and quality use of medicines used by young people
      in Australia?

PMID- 28488750
TI  - Computing the Extended Synthesis: Mapping the Dynamics and Conceptual Structure
      of the Evolvability Research Front.
AB  - Since the late 1970s, the field of evolutionary biology has undergone empirical
      and theoretical developments that have threaten the pillars of evolutionary
      theory. Some evolutionary biologists have recently argued that evolutionary
      biology is not experiencing a paradigm shift, but an expansion of the modern
      synthesis. Philosophers of biology focusing on scientific practices seem to agree
      with this pluralistic interpretation and have argued that evolutionary theory
      should rather be seen as an organized network of multiple problem agendas with
      diverse disciplinary contributors. In this paper, I apply a computational
      analysis to study the dynamics and conceptual structure of one of the main
      emerging problem agendas in evolutionary biology: evolvability. I have used
      CiteSpace, an application for visualizing and analyzing trends and patterns in
      scientific literature that applies cocitation analysis to identify scientific
      specialities. I analyze the main clusters of the evolvability cocitation network
      with the aim to identify the main research lines and the interdisciplinary
      relationships that structure this research front. I then compare these results
      with the existing classifications of evolvability concepts, and identify four
      main conceptual tensions within the definitions of evolvability. Finally, I argue
      that there is a lot of usefulness in the inconsistency in which the term
      evolvability is used in biological research. I claim that evolvability research
      has set up "trading zones" in biology that make possible interdisciplinary
      exchanges.

PMID- 28488751
TI  - Consistent Infection Prevention: Vital During Routine and Emerging Infectious
      Diseases Care

PMID- 28488752
TI  - Functional structure of the bromeliad tank microbiome is strongly shaped by local
      geochemical conditions.
AB  - Phytotelmata in tank-forming Bromeliaceae plants are regarded as potential
      miniature models for aquatic ecology, but detailed investigations of their
      microbial communities are rare. Hence, the biogeochemistry in bromeliad tanks
      remains poorly understood. Here we investigate the structure of bacterial and
      archaeal communities inhabiting the detritus within the tanks of two bromeliad
      species, Aechmea nudicaulis and Neoregelia cruenta, from a Brazilian sand dune
      forest. We used metagenomic sequencing for functional community profiling and 16S
      sequencing for taxonomic profiling. We estimated the correlation between
      functional groups and various environmental variables, and compared communities
      between bromeliad species. In all bromeliads, microbial communities spanned a
      metabolic network adapted to oxygen-limited conditions, including all
      denitrification steps, ammonification, sulfate respiration, methanogenesis,
      reductive acetogenesis and anoxygenic phototrophy. Overall, CO2 reducers
      dominated in abundance over sulfate reducers, and anoxygenic phototrophs largely
      outnumbered oxygenic photoautotrophs. Functional community structure correlated
      strongly with environmental variables, between and within a single bromeliad
      species. Methanogens and reductive acetogens correlated with detrital volume and
      canopy coverage, and exhibited higher relative abundances in N. cruenta. A
      comparison of bromeliads to freshwater lake sediments and soil from around the
      world, revealed stark differences in terms of taxonomic as well as functional
      microbial community structure.

PMID- 28488753
TI  - Cascades of Interrupted Pummerer Reaction-Sigmatropic Rearrangement.
AB  - A new class of Pummerer chemistry has emerged as a powerful tool in organic
      synthesis. The new technology consists of a beautiful cascade of an interrupted
      Pummerer reaction and the subsequent [3,3] sigmatropic rearrangement. The
      interrupted Pummerer reactions of alkenyl or aryl sulfoxides with unsaturated
      nucleophiles such as allylic silanes, ketones, and phenols provide sulfonium
      intermediates, which are ready to undergo smooth charge-accelerated [3,3]
      sigmatropic rearrangement with excellent to exclusive regioselectivity. Some of
      the transformations proceed with transient loss of aromaticity. The reactions
      afforded five-membered heterocycles, benzofurans, and biaryls of importance,
      depending on the sulfoxides and nucleophiles used. The reactions are unique and
      game-changing because they are efficient, robust, redox-neutral, regioselective,
      and metal-free, which perfectly fits the need of modern organic synthesis. This
      chemistry also underscores the synthetic potential of organosulfur chemistry.

PMID- 28488754
TI  - Virtual endovascular treatment of intracranial aneurysms: models and uncertainty.
AB  - Virtual endovascular treatment models (VETMs) have been developed with the view
      to aid interventional neuroradiologists and neurosurgeons to pre-operatively
      analyze the comparative efficacy and safety of endovascular treatments for
      intracranial aneurysms. Based on the current state of VETMs in aneurysm rupture
      risk stratification and in patient-specific prediction of treatment outcomes, we
      argue there is a need to go beyond personalized biomechanical flow modeling
      assuming deterministic parameters and error-free measurements. The
      mechanobiological effects associated with blood clot formation are important
      factors in therapeutic decision making and models of post-treatment intra
      aneurysmal biology and biochemistry should be linked to the purely hemodynamic
      models to improve the predictive power of current VETMs. The influence of model
      and parameter uncertainties associated to each component of a VETM is, where
      feasible, quantified via a random-effects meta-analysis of the literature. This
      allows estimating the pooled effect size of these uncertainties on aneurysmal
      wall shear stress. From such meta-analyses, two main sources of uncertainty
      emerge where research efforts have so far been limited: (1) vascular wall
      distensibility, and (2) intra/intersubject systemic flow variations. In the
      future, we suggest that current deterministic computational simulations need to
      be extended with strategies for uncertainty mitigation, uncertainty exploration,
      and sensitivity reduction techniques. WIREs Syst Biol Med 2017, 9:e1385. doi:
      10.1002/wsbm.1385 For further resources related to this article, please visit the
      WIREs website.

PMID- 28488755
TI  - Frequency-Dependent Habituation Deficit of the Nociceptive Blink Reflex in Aura
      With Migraine Headache. Can Migraine Aura Modulate Trigeminal Excitability?
AB  - OBJECTIVE: To study the influence of the migraine aura on the trigeminal
      nociception, we investigated the habituation of the nociceptive blink reflex
      (nBR) R2 responses in aura with migraine headache (AwMH) and comparatively in
      migraine without aura (MWoA) and healthy subjects (HS). BACKGROUND: A clear
      deficit of habituation in trigeminal nociceptive responses has been documented in
      MWoA; however, similar data in MWA are lacking. METHODS: Seventeen AwMH, 29 MWoA,
      and 30 HS were enrolled and a nonrandomized clinical neurophysiological study
      examining nBR habituation by clinical diagnosis was devised. We delivered a
      series of 26 electrical stimuli, at different stimulation frequencies (SF) (0.05,
      0.1, 0.2, 0.3, 0.5, and 1 Hz), subsequently subdivided in five blocks of five
      responses for each SF. The mean area values of the second to the fifth block
      expressed as the percentage of the mean area value of the first block were taken
      as an index of habituation for each SF. RESULTS: A significant lower mean
      percentage decrease of the R2 area across all blocks was found at 1, 0.5, 0.3,
      and 0.2 Hz SF in MWoA and at 0.3 and 0.2 Hz SF in AwMH, when compared to HS. In
      the most representative fifth block of responses, we found in MWoA vs HS at 1 Hz,
      57.0 +/- 27.8 vs 30.6 +/- 12.0; at 0.5 Hz, 54.8 +/- 26.1 vs 32.51 +/- 17.7; at
      0.3 Hz, 44.7 +/- 21.6 vs 27.6 +/- 13.2; at 0.2 Hz, 61.3 +/- 29.5 vs 32.6 +/-
      18.0, and in AwMH vs HS at 0.3 Hz, 52.7 +/- 24.7 vs 27.6 +/- 13.2; at 0.2 Hz,
      69.3 +/- 38.6 vs 32.6 +/- 18.0 as mean +/- SD of the R2 area percentage of the
      first block, respectively. Interestingly, AwMH subjects did not show differences
      in mean percentage decrease of the R2 area at 1 and 0.5 Hz SF when compared to
      HS. No differences between groups were found at 0.1 and 0.05 Hz SF. CONCLUSIONS:
      We demonstrated in AwMH a deficit of habituation of the nBR R2 responses after
      repeated stimulations, although less pronounced than that observed in MWoA of
      comparable clinical severity. We hypothesize that AwMH and MWoA share some
      pathogenetic aspects, and also that migraine aura physiopathology may play a
      modulating role on the excitability of the nociceptive trigeminal pathways.

PMID- 28488756
TI  - Cyclic Vomiting Syndrome in Adults and Children: A Hypothesis.
AB  - OBJECTIVE: To see how patients' clinical descriptions compare to the third
      classification of International Classification of Headache Disorders (ICHD-III
      beta). BACKGROUND: CVS is an episodic syndrome associated with migraine. It is a
      rare disorder of childhood and adulthood. New criteria are proposed in the third
      classification of International Classification of Headache Disorders. METHODS:
      This study describes children and adults' CVS characteristics at a French
      tertiary-care center, according to the ICHD-II and ICHD-III beta criteria.
      Clinical features, and results of paraclinical tests were characterized. RESULTS:
      Fifteen patients were included: 8 adults, 2 children, and 5 adolescents. Familial
      history of migraine or CVS was respectively noticed in 12 and 4 patients. The
      duration of premonitory, emetic, and postdromal phases was evaluated from hours
      to days. Some symptoms described in theses phases are also described in
      migrainous population, with a comparable frequency. Cranial or systemic autonomic
      symptoms were respectively reported in 47% and 93%. Nine patients described a
      circadian periodicity, and six patients described a circannual periodicity. The
      predictable periodicity was from 1 week to 12 months. A brain perfusion SPECT
      showed an increased hypothalamic perfusion during emetic phase in one patient.
      CONCLUSIONS: CVS is a rare episodic syndrome associated with migraine. Some
      clinical features and paraclincal tests suggest a chronobiological disease.

PMID- 28488757
TI  - Stimulation of Pol III-dependent 5S rRNA and U6 snRNA gene expression by AP-1
      transcription factors.
AB  - RNA polymerase III transcribes structurally diverse group of essential noncoding
      RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are
      involved in RNA processing and ribosome biogenesis, thus, coupling Pol III
      activity to the rate of protein synthesis, cell growth, and proliferation. Even
      though a few Pol II-associated transcription factors have been reported to
      participate in Pol III-dependent transcription, its activation by activator
      protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show
      that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA
      (type I) and U6 snRNA (type III) gene promoters and stimulate their
      transcription. Our chromatin immunoprecipitation studies suggested that
      endogenous AP-1 factors bind to their cognate promoter elements during the G1/S
      transition of cell cycle apparently synchronous with Pol III transcriptional
      activity. Furthermore, the interaction of c-Jun with histone acetyltransferase
      p300 promoted the recruitment of p300/CBP complex on the promoters and
      facilitated the occupancy of Pol III transcriptional machinery via histone
      acetylation and chromatin remodeling. The findings of our study, together,
      suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6
      snRNA expression with a potential role in cell proliferation.

PMID- 28488758
TI  - Engineered Humicola insolens cutinase for efficient cellulose acetate
      deacetylation.
AB  - Cutinases comprise a family of esterases with broad hydrolytic activity for chain
      and pendant ester groups. This work aimed to identify and improve an efficient
      cutinase for cellulose acetate (CA) deacetylation. The development of a mild
      method for CA fiber surface deacetylation will result in improved surface
      hydrophilicity and reactivity while, when combined with cellulases, a route to
      the full recycling of CA to acetate and glucose. In this study, the comparative
      CA deacetylation activity of four homologous wild-type (wt) fungal cutinases from
      Aspergillus oryzae (AoC), Thiellavia terrestris (TtC), Fusarium solani (FsC), and
      Humicola insolens (HiC) was determined by analysis of CA deacetylation kinetics.
      wt-HiC had the highest catalytic efficiency (~32 [cm2 L-1 ]-1 h-1 ). Comparison
      of wt-cutinase catalytic constants revealed that differences in catalytic
      efficiency are primarily due to corresponding variations in corresponding
      substrate binding constants. Docking studies with model tetrameric substrates
      also revealed structural origins for differential substrate binding amongst these
      cutinases. Comparative docking studies of HiC point mutations led to the
      identification of two important rationales for engineering cutinases for CA
      deacetylation: (i) create a tight but not too closed binding groove, (ii) allow
      for hydrogen bonding in the extended region around the active site. Rationally
      designed HiC with amino acid substitutions I36S, predicted to hydrogen bond to
      CA, combined with F70A, predicted to remove steric constraints, showed a two-fold
      improvement in catalytic efficiency. Continued cutinase optimization guided by a
      detailed understanding of structure-activity relationships, as demonstrated here,
      will be an important tool to developing practical cutinases for commercial green
      chemistry technologies.

PMID- 28488759
TI  - Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality
      risk among Brazilian Amazon riparian elderly population.
AB  - OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several
      functions on brain and peripheral tissues via different receptors. The gene for
      the 5-HT2A receptor shows some variations, including a T102C polymorphism, that
      have been associated with increased risk of neuropsychiatric and vascular
      disorders. However, the potential impact of 5-HT2A imbalance caused by genetic
      variations on the human lifespan has not yet been established. METHODS: We
      performed a prospective study involving an Amazon riparian elderly free-living
      population in Maues City, Brazil, with a 5-year follow-up. Out of a cohort of 637
      subjects selected in July, 2009, we genotyped 471 individuals, including 209
      males (44.4%) and 262 females (55.6%), all averaging 72.3 +/- 7.8 years of age
      (ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were
      14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the
      period investigated, we observed significantly (P = .005) higher numbers of TT
      carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers
      (12.5%). Cox-regression analysis showed that association between the T102C-SNP
      and elderly survival was independent of age, sex, and other health variables.
      CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause
      significant disturbances that lead to an increased susceptibility to death for
      individuals who are over 60 years of age.

PMID- 28488760
TI  - Dysregulated Metabolism of the Amyloid-beta Protein and Therapeutic Approaches in
      Alzheimer Disease.
AB  - Amyloid-beta protein (Abeta) is the main component of senile plaques in the
      brains of Alzheimer disease (AD) patients. Abeta is proteolytically derived from
      amyloid-beta precursor protein by beta- and gamma-secretases. Secreted Abeta is
      then eliminated from the central nervous system by multiple clearance mechanisms,
      including phagocytosis, immune responses, and proteolytic degradation. These
      dynamic metabolic processes, which are referred to as Abeta economy, regulate
      steady-state brain Abeta levels. Familial AD-linked genetic mutations augment the
      production and aggregation of Abeta. In contrast, rare genetic variants that
      reduce Abeta production were protective against AD. Moreover, decreased Abeta
      clearance has been demonstrated in sporadic AD patients, suggesting that
      dysregulation of Abeta economy contributes to the development of AD. Thus,
      several approaches to inhibit the production as well as to enhance the clearance
      of Abeta have been investigated as potential therapeutics against AD. In this
      manuscript, we introduce the molecules and cellular mechanisms involved in the
      regulation of Abeta economy and discuss the current understanding of these
      processes in the development of therapeutics against AD. J. Cell. Biochem. 118:
      4183-4190, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28488761
TI  - Apoptotic sperm biomarkers and the correlation between conventional sperm
      parameters and clinical characteristics.
AB  - The principal aim of this retrospective study was to examine the relationship
      between sperm apoptotic biomarkers and the patient's biclinical characteristics,
      the conventional sperm parameters and the results of assisted reproductive
      technology. Sperm analysis, activated caspases, annexin V staining for
      phosphatidylserine (PS) externalisation and labelling assay for DNA fragmentation
      were assessed in 122 males of infertile couples. Fifty-seven couples were
      allocated to the natural conception group, and 65 couples underwent IVF or ICSI.
      Semen of IVF/ICSI patients showed a higher proportion of apoptotic spermatozoa in
      their spermatozoa when compared with a natural conception group (p < .05). Sperm
      apoptotic biomarkers correlated with age, FSH, and conventional sperm parameters.
      DNA fragmentation correlated positively with the percentage of semen having
      externalised PS (r = .78, p = 0) and activated caspases (r = .71, p = 0).
      Patients without clinical pregnancy had higher frequency of DNA fragmentation,
      externalised PS and activated caspases compared to patients with clinical
      pregnancy (p < .001). The best specificity and greater sensitivity were obtained
      with the test of the DNA fragmentation compared to the other biomarkers. Among
      the apoptotic biomarkers, only DNA fragmentation was found to predict natural or
      assisted pregnancy better than conventional sperm parameters.

PMID- 28488762
TI  - Visual Auras in Epilepsy and Migraine - An Analysis of Clinical Characteristics.
AB  - OBJECTIVE: To evaluate the characteristics of visual auras (VA) in epilepsy and
      migraine. BACKGROUND: Both disorders are usually diagnosed on clinical grounds,
      but differentiation might be challenging in isolated auras or because of the
      similar presentation in migraine and epilepsy. METHODS: A retrospective study of
      two cohorts was performed to compare the VA characteristics of 27 epilepsy
      patients and 27 age-matched migraine patients. RESULTS: The duration of VA was
      significantly shorter in epilepsy (median: 56s; 1st quartile Q1: 26s; 3rd
      quartile Q3: 130s) than in migraine (20 min; Q1: 10 min; Q3: 30 min) (P < .0001).
      A cutoff duration of >=5 minutes identified all migraine patients (100%
      sensitivity, 92% specificity). VAs of epileptic etiology were characterized by
      restriction to a visual hemifield (74.1% vs 29.6% in migraine, P = .0024) with
      stereotypic affection of one hemifield (55.5% vs 7.4% in migraine, P = 0.0003).
      Centrifugal or centripetal spread of visual phenomena only occurred in migraine
      (37.0%), but not in epilepsy (P = 0.0007). If present, accompanying symptoms such
      as nausea/vomiting (19/27) or photo-/phonophobia (17/27) identify migrainous
      auras (vs 0/27 in the epilepsy patients; P < .0001). Headache presented in all
      migraine patients, but was also observed in six of the epilepsy patients during
      cephalic auras or the postictal phase (P < .0001). None of the visual migrainous
      auras evolved into an epileptic seizure, a concept called migralepsy.
      CONCLUSIONS: Several clinical characteristics differentiate VA of epileptic and
      migrainous origin - if presenting in classical manner. Additional EEG evaluations
      should be performed in patients with VA of unclear etiology and epileptic VA
      features added to current classifications to increase their discriminatory power.

PMID- 28488763
TI  - Recent Progress in the Design of Advanced Cathode Materials and Battery Models
      for High-Performance Lithium-X (X = O2 , S, Se, Te, I2 , Br2 ) Batteries.
AB  - Recent advances and achievements in emerging Li-X (X = O2 , S, Se, Te, I2 , Br2 )
      batteries with promising cathode materials open up new opportunities for the
      development of high-performance lithium-ion battery alternatives. In this review,
      we focus on an overview of recent important progress in the design of advanced
      cathode materials and battery models for developing high-performance Li-X (X = O2
      , S, Se, Te, I2 , Br2 ) batteries. We start with a brief introduction to explain
      why Li-X batteries are important for future renewable energy devices. Then, we
      summarize the existing drawbacks, major progress and emerging challenges in the
      development of cathode materials for Li-O2 (S) batteries. In terms of the
      emerging Li-X (Se, Te, I2 , Br2 ) batteries, we systematically summarize their
      advantages/disadvantages and recent progress. Specifically, we review the
      electrochemical performance of Li-Se (Te) batteries using carbonate-/ether-based
      electrolytes, made with different electrode fabrication techniques, and of Li-I2
      (Br2 ) batteries with various cell designs (e.g., dual electrolyte, all-organic
      electrolyte, with/without cathode-flow mode, and fuel cell/solar cell
      integration). Finally, the perspective on and challenges for the development of
      cathode materials for the promising Li-X (X = O2 , S, Se, Te, I2 , Br2 )
      batteries is presented.

PMID- 28488764
TI  - Astrocytes contribute to Abeta-induced blood-brain barrier damage through
      activation of endothelial MMP9.
AB  - The blood-brain barrier (BBB) plays an important role in the maintenance of the
      brain homeostasis, and its proper functions are warranted by the interplay
      between different cellular components (endothelial cells, astrocytes and
      pericytes). BBB dysfunctions in pathological conditions, and particularly in
      Alzheimer's disease, have been documented. Here, using an in vitroBBB model, the
      interaction between endothelial cells and astrocytes exposed to Abeta1-42 was
      investigated. Human endothelial cells, cultured in monolayer or co-cultured with
      astrocytes, were exposed to Abeta1-42 (2 MUM for 18 h). Abeta induced dysfunction
      of endothelial barrier, as assessed by enhanced permeability to FITC-conjugated
      dextran and reduced expression of claudin-5; these modifications were observed in
      the co-culture model, but not in endothelial cells cultured in monolayer.
      Similarly, Abeta-induced damage at the barrier was observed when endothelial
      cells were challenged in the presence of conditioned medium generated by
      astrocytes previously exposed to Abeta (ACM Abeta). Endothelial barrier damages
      were associated with enhanced matrix metalloprotease 9 (MMP9) activity, known to
      mediate claudin-5 disruption. These events were not related to the direct effects
      played by Abeta on endothelial cells, but they were rather the consequence of
      Abeta-induced vascular endothelial growth factor (VEGF) expression in astrocytes.
      Indeed, when vascular endothelial growth factor expression was down-regulated in
      astrocytes, neither barrier properties or MMP9 expression in endothelial cells
      were affected after Abeta exposure both in the co-culture model or in the
      presence of ACM Abeta. These data point out the importance of astrocytes'
      mediation in inducing endothelial sensitivity to Abeta1-42.

PMID- 28488765
TI  - Antitumoral potential, antioxidant activity and carotenoid content of two
      Southern Italy tomato cultivars extracts: San Marzano and Corbarino.
AB  - Gastric cancer represents a diffuse and aggressive neoplasm, whose mortality
      index is among the highest in the world. Predisposing factors are E-cadherin
      mutations, Helicobacter pylori infection, and a diet rich in salted and smoked
      food, with a low intake of fresh fruits and vegetables. Here, we analyzed the
      effect of total lipophilic extracts of two Southern Italy tomato varieties, San
      Marzano and Corbarino, on an in vitro model of gastric cancer, YCC-1, YCC-2 and
      YCC-3 cell lines, characterized by different aggressiveness. Our results showed a
      possible role of these two varieties of tomatoes against typical neoplastic
      features. The treatment with tomato extracts affected cancer cell ability to grow
      both in adherence and in semisolid medium, reducing also cell migration ability.
      No toxic effects were observed on non-tumoral cells. We found, on gastric cancer
      cell lines, effects on both cell cycle progression and apoptosis modulation. The
      extent of antineoplastic effects, however, did not seem to correlate with the
      carotenoid content and antioxidant activity of the two tomato varieties. Our data
      indicate that San Marzano and Corbarino intake might be further considered as
      nutritional support not only in cancer prevention, but also for cancer patient
      diet.

PMID- 28488766
TI  - Brief isoflurane anesthesia regulates striatal AKT-GSK3beta signaling and
      ameliorates motor deficits in a rat model of early-stage Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative movement disorder
      primarily affecting the nigrostriatal dopaminergic system. The link between
      heightened activity of glycogen synthase kinase 3beta (GSK3beta) and neurodegene
      rative processes has encouraged investigation into the potential disease
      modifying effects of novel GSK3beta inhibitors in experimental models of PD.
      Therefore, the intriguing ability of several anesthetics to readily inhibit
      GSK3beta within the cortex and hippocampus led us to investigate the effects of
      brief isoflurane anesthesia on striatal GSK3beta signaling in naive rats and in a
      rat model of early-stage PD. Deep but brief (20-min) isoflurane anesthesia
      exposure increased the phosphorylation of GSK3beta at the inhibitory Ser9
      residue, and induced phosphorylation of AKTThr308 (protein kinase B; negative
      regulator of GSK3beta) in the striatum of naive rats and rats with unilateral
      striatal 6-hydroxydopamine (6-OHDA) lesion. The 6-OHDA protocol produced gradual
      functional deficiency within the nigrostriatal pathway, reflected as a preference
      for using the limb ipsilateral to the lesioned striatum at 2 weeks post 6-OHDA.
      Interestingly, such motor impairment was not observed in animals exposed to four
      consecutive isoflurane treatments (20-min anesthesia every 48 h; treatments
      started 7 days after 6-OHDA delivery). However, isoflurane had no effect on
      striatal or nigral tyrosine hydroxylase (a marker of dopaminergic neurons)
      protein levels. This brief report provides promising results regarding the
      therapeutic potential and neurobiological mechanisms of anesthetics in
      experimental models of PD and guides development of novel disease-modifying
      therapies.

PMID- 28488767
TI  - An assessment of postcranial indices, ratios, and body mass versus eco
      geographical variables of prehistoric Jomon, Yayoi agriculturalists, and Kumejima
      Islanders of Japan.
AB  - OBJECTIVES: We explore variations in body and limb proportions of the Jomon
      hunter-gatherers (14,000-2500 BP), the Yayoi agriculturalists (2500-1700 BP) of
      Japan, and the Kumejima Islanders of the Ryukyus (1600-1800 AD) with 11
      geographically diverse skeletal postcranial samples from Africa, Europe, Asia,
      Australia, and North America using brachial-crural indices, femur head-breadth-to
      femur length ratio, femur head-breadth-to-lower-limb-length ratio, and body mass
      as indicators of phenotypic climatic adaptation. Specifically, we test the
      hypothesis that variation in limb proportions seen in Jomon, Yayoi, and Kumejima
      is a complex interaction of genetic adaptation; development and allometric
      constraints; selection, gene flow and genetic drift with changing cultural
      factors (i.e., nutrition) and climate. METHODS: The skeletal data (1127
      individuals) were subjected to principle components analysis, Manly's permutation
      multiple regression tests, and Relethford-Blangero analysis. RESULTS: The results
      of Manly's tests indicate that body proportions and body mass are significantly
      correlated with latitude, and minimum and maximum temperatures while limb
      proportions were not significantly correlated with these climatic variables.
      Principal components plots separated "climatic zones:" tropical, temperate, and
      arctic populations. The indigenous Jomon showed cold-adapted body proportions and
      warm-adapted limb proportions. Kumejima showed cold-adapted body proportions and
      limbs. The Yayoi adhered to the Allen-Bergmann expectation of cold-adapted body
      and limb proportions. Relethford-Blangero analysis showed that Kumejima
      experienced gene flow indicated by high observed variances while Jomon
      experienced genetic drift indicated by low observed variances. CONCLUSIONS: The
      complex interaction of evolutionary forces and development/nutritional
      constraints are implicated in the mismatch of limb and body proportions.

PMID- 28488768
TI  - Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a
      form of autophagy in 3T3-L1 adipocytes.
AB  - Obesity is characterized by an excessive triacylglycerol accumulation in white
      adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol
      storage and mobilization by lipid droplet-associated proteins as well as
      lipolytic enzymes have been identified. Increasing energy expenditure by inducing
      a mild uncoupling of mitochondria in adipocytes might represent a putative
      interesting anti-obesity strategy as it reduces the adipose tissue
      triacylglycerol content (limiting alterations caused by cell hypertrophy) by
      stimulating lipolysis through yet unknown mechanisms, limiting the adverse
      effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in
      lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes
      were characterized. Mitochondrial uncoupling-induced lipolysis was found to be
      independent from canonical pathways that involve lipolytic enzymes such as HSL
      and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling
      relies on a form of autophagy as lipid droplets are captured by endolysosomal
      vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed
      to mild uncoupling provides new insights on the biology of adipocytes dealing
      with mitochondria forced to dissipate energy.

PMID- 28488769
TI  - Selective expression of long non-coding RNAs in a breast cancer cell progression
      model.
AB  - Long non-coding RNAs (lncRNAs) are acknowledged as regulators of cancer biology
      and pathology. Our goal was to perform a stringent profiling of breast cancer
      cell lines that represent disease progression. We used the MCF-10 series, which
      includes the normal-like MCF-10A, HRAS-transformed MCF-10AT1 (pre-malignant), and
      MCF-10CA1a (malignant) cells, to perform transcriptome wide sequencing. From
      these data, we have identified 346 lncRNAs with dysregulated expression across
      the progression series. By comparing lncRNAs from these datasets to those from an
      additional set of cell lines that represent different disease stages and
      subtypes, MCF-7 (early stage, luminal), and MDA-MB-231 (late stage, basal), 61
      lncRNAs that are associated with breast cancer progression were identified.
      Querying breast cancer patient data from The Cancer Genome Atlas, we selected a
      lncRNA, IGF-like family member 2 antisense RNA 1 (IGFL2-AS1), of potential
      clinical relevance for functional characterization. Among the 61 lncRNAs, IGFL2
      AS1 was the most significantly decreased. Our results indicate that this lncRNA
      plays a role in downregulating its nearest neighbor, IGFL1, and affects migration
      of breast cancer cells. Furthermore, the lncRNAs we identified provide a valuable
      resource to mechanistically and clinically understand the contribution of lncRNAs
      in breast cancer progression.

PMID- 28488770
TI  - Allopurinol for the Treatment of Refractory Aggression: A Case Series.
AB  - OBJECTIVE: Allopurinol is a drug indicated for the treatment and prevention of
      gout. Through various theorized mechanisms, there has been an observed benefit in
      reducing aggression in patients with dementia who are refractory to traditional
      interventions. This case series of eight patients reports the use of allopurinol
      to treat aggression at the Battle Creek Veterans Affairs Medical Center. METHODS:
      Charts of research participants were accessed retrospectively to obtain data.
      Adverse event notes were evaluated to identify the number of aggressive events
      before the initiation of allopurinol compared with the total number and rates of
      aggressive events after the initiation of allopurinol. RESULTS: A total of eight
      patients were included in the case series. Of those started on allopurinol for
      treating aggression, two showed no effect while all other participants responded
      with a decrease in the number and rate of reported aggressive episodes.
      CONCLUSIONS: Allopurinol was observed to decrease the number and rate of
      aggressive events in patients refractory to other treatments.

PMID- 28488771
TI  - Fluorinated surfaces: smart substrates for matrix-free laser desorption
      ionization.

PMID- 28488772
TI  - Active application of primer acid on acid-treated enamel: Influence on the bond
      effectiveness of self-etch adhesives systems.
AB  - AIM: Evaluate the composite-to-enamel bond after passive or active application of
      self-etching primer systems on polished or pre-etched enamel with phosphoric
      acid. MATERIALS AND METHODS: Two self-etch adhesives systems (SEAS) were used:
      Clearfil SE Bond and Easy Bond. Third human molars were divided into 8 groups (N
      = 10). The crown of each tooth was sectioned into halves and the mesial/distal
      surfaces were used. The adhesives were actively or passively applied on enamel
      with or without prior phosphoric-acid etching. Resin composite cylinders were
      built after adhesive application. After stored in relative humidity for 24 hr/37
      degrees C the specimens were subjected to microshear test in universal testing a
      machine at a crosshead speed of 0.5 mm/minute. The results were analyzed with
      three-way ANOVA and the Tukey test. The enamel-etching pattern was evaluated
      under SEM. RESULTS: The 2-step SEAS system presented significantly higher
      adhesive bond strength means (47.37 MPa) than the 1-step (36.87 MPa). A poor
      enamel- etching pattern was observed in active mode showing irregular and short
      resin tags, however there was not compromised the bond strength. CONCLUSION:
      Active or passive application produced similar values of bond strength to enamel
      regardless of enamel pretreatment and type of SEAS.

PMID- 28488773
TI  - Large Modulation of Charge Carrier Mobility in Doped Nanoporous Organic
      Transistors.
AB  - Molecular doping of organic electronics has shown promise to sensitively modulate
      important device metrics. One critical challenge is the disruption of structure
      order upon doping of highly crystalline organic semiconductors, which
      significantly reduces the charge carrier mobility. This paper demonstrates a new
      method to achieve large modulation of charge carrier mobility via channel doping
      without disrupting the molecular ordering. Central to the method is the
      introduction of nanopores into the organic semiconductor thin films via a simple
      and robust templated meniscus-guided coating method. Using this method, the
      charge carrier mobility of C8 -benzothieno[3,2-b]benzothiophene transistors is
      boosted by almost sevenfold. This paper further demonstrates enhanced electron
      transport by close to an order of magnitude in a diketopyrrolopyrrole-based donor
      acceptor polymer. Combining spectroscopic measurements, density functional theory
      calculations, and electrical characterizations, the doping mechanism is
      identified as partial-charge-transfer induced trap filling. The nanopores serve
      to enhance the dopant/organic semiconductor charge transfer reaction by exposing
      the pi-electrons to the pore wall.

PMID- 28488774
TI  - FSCN1 is upregulated by SNAI2 and promotes epithelial to mesenchymal transition
      in head and neck squamous cell carcinoma.
AB  - In this study, we investigated whether there is any association between the
      expression of FSCN1 and SNAI2 and the possible underlying mechanisms in head and
      neck squamous cell carcinoma (HNSC). In addition, we also investigated whether
      FSCN1 modulates epithelial-to-mesenchymal transition (EMT) in HNSC cells.
      Microarray data of dysregulated genes in HNSC were searched in GEO datasets. The
      association between FSCN1 expression and the 5-year/10-year overall survival
      (OS), as well as the correlation between the expression of FSCN1 and SOX2, MYBL2,
      SNAI2, STAT1, and SOX4, was analyzed based on data in TCGA HNSC cohort (TCGA
      HNSC). The binding site of SNAI2 in FSCN1 promoter was verified using luciferase
      reporter assay. SCC9 and SCC15 cells were transfected with pCMV-SNAI2 or pCMV
      FSCN1 expression vector or the empty control. Alteration of E-cadherin, Claudin
      1, Vimentin, and N-cadherin was then quantified. Our results showed that FSCN1 is
      significantly upregulated in HNSC tissues compared with the normal control
      tissues. High FSCN1 expression is associated with worse 5-year and 10-year OS
      among the HNSC patients. Bioinformatic prediction showed a highly possible SNAI2
      binding site in FSCN1 promoter and following luciferase reporter assay verified
      this site. SNAI2 overexpression significantly increased FSCN1 expression at both
      mRNA and protein level. FSCN1 overexpression reduced the expression of E-cadherin
      and Claudin 1, but increased the expression of Vimentin and N-cadherin in SCC9
      and SCC-15 cells. Therefore, we infer that FSCN1 is a downstream effector of
      SNAI2 in promoting EMT in HNSC cells.

PMID- 28488775
TI  - Effects of Sorbic Acid-Chitosan Microcapsules as Antimicrobial Agent on the
      Properties of Ethylene Vinyl Alcohol Copolymer Film for Food Packaging.
AB  - This paper discusses the possibility of using sorbic acid-chitosan microcapsules
      (S-MPs) as an antibacterial component of active ethylene vinyl alcohol copolymer
      (EVOH) film. S-MPs with a diameter of approximately 1 to 4 MUm showed a sorbic
      acid loading capacity of 46.5%. Addition of S-MPs (3%, w/w) increased the tensile
      strength, haze, oxygen, and water vapor barrier properties, as well as reduced
      the elongations at break and transmittance of S-MPs-EVOH (S-MP-EVOH) film.
      Antibacterial tests showed that the inhibitory capacity of S-MP-EVOH film against
      Salmonella Enteritidis and Escherichia coli was higher than that against Listeria
      monocytogenes. Moreover, the antibacterial effect of sorbic acid-EVOH (S-EVOH)
      film was stronger than that of S-MP-EVOH film. However, S-MP-EVOH film
      demonstrated a longer effective time than S-EVOH film. Using the total viable
      counts and total volatile base nitrogen as the judgment standard, S-MP
      EVOH/polyethylene terephthalate (PET) composite film could extend the shelf life
      of fish fillets by 4 d at 4  degrees C, compared with EVOH/PET film. For this
      reason, S-MP could be a potential antibacterial component of active films.

PMID- 28488776
TI  - Optochemically Responsive 2D Nanosheets of a 3D Metal-Organic Framework Material.
AB  - Outstanding functional tunability underpinning metal-organic framework (MOF)
      confers a versatile platform to contrive next-generation chemical sensors,
      optoelectronics, energy harvesters, and converters. A rare exemplar of a porous
      2D nanosheet material constructed from an extended 3D MOF structure is reported.
      A rapid supramolecular self-assembly methodology at ambient conditions to
      synthesize readily exfoliatable MOF nanosheets, functionalized in situ by
      adopting the guest@MOF (host) strategy, is developed. Nanoscale confinement of
      light-emitting molecules (as functional guest) inside the MOF pores generates
      unusual combination of optical, electronic, and chemical properties, arising from
      the strong host-guest coupling effects. Highly promising photonics-based chemical
      sensing opened up by the new guest@MOF composite systems is shown. By harnessing
      host-guest optochemical interactions of functionalized MOF nanosheets, detection
      of an extensive range of volatile organic compounds and small molecules important
      for many practical applications has been accomplished.

PMID- 28488777
TI  - MicroRNA-224-5p regulates adipocyte apoptosis induced by TNFalpha via controlling
      NF-kappaB activation.
AB  - Tumor necrosis factor (TNF) alpha can induce cell apoptosis and activate nuclear
      transcription (NF)-kappaB in different cell types. Activated NF-kappaB further
      promotes or suppresses cellular apoptosis in different cases. The present study
      explored the effect of activated NF-kappaB on adipocyte apoptosis induced by
      TNFalpha and which microRNAs (miRNAs) were involved in the process. Our findings
      demonstrated that treatment of differentiated 3T3-L1 adipocytes with TNFalpha (20
      ng/mL) rapidly activated NF-kappaB and induced moderate apoptosis.
      Pyrrolidinedithiocarbamic acid (PDTC, 60 uM), a specific NF-kappaB inhibitor,
      abated NF-kappaB activation that rendered the adipocytes vulnerable to TNFalpha
      induced apoptosis. Dozens of miRNAs exhibited significant expression changes
      following TNFalpha treatment and the addition of PDTC. In which, miRNA-224-5p
      (miR-224) was up-regulated by TNFalpha exposure but down-regulated by PDTC
      addition. Furthermore, over-expression of miR-224 promoted NF-kappaB activation
      and prevented the adipocyte apoptosis induced by TNFalpha, while miR-224
      deficiency showed the opposite effects. The TRAF-associated NF-kappaB activator
      (TANK) gene was identified as a direct target of miR-224 by computational and
      luciferase reporter assays. Additionally, silencing the TANK gene by the small
      interfering RNA similarly promoted NF-kappaB activation and attenuated the
      cellular apoptosis. In conclusion, these findings demonstrate that miR-224 plays
      an essential role in adipocyte apoptosis caused by TNFalpha through control of NF
      kappaB activation via targeting the TANK gene.

PMID- 28488778
TI  - Total Syntheses of Lepadiformine Marine Alkaloids with Enantiodivergency,
      Utilizing Hg(OTf)2 -Catalyzed Cycloisomerization Reaction and their Cytotoxic
      Activities.
AB  - The enantioselective total syntheses of lepadiformine marine alkaloids,
      azatricyclic natural products isolated from marine tunicates, were completed.
      These alkaloids have a unique chemical structure characterized by the trans-1
      azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system).
      Here we found that a cycloisomerization reaction from functionalized linear
      substrates to a 1-azaspiro[4.5]decane framework corresponding to the AC ring in
      lepadiformines is promoted by a catalytic amount of mercury(II) triflate
      (Hg(OTf)2 ). The total syntheses of (-)-lepadiformines A and B were achieved in
      28 % and 21 % overall yields, respectively, through the novel cycloisomerization
      reaction. The syntheses of (+)- and (-)-lepadiformine C hydrochloride salts also
      enabled us to determine the absolute configuration of natural lepadiformine C. It
      has been found that a phenomenon of enantiodivergence occurs in lepadiformine
      alkaloids from a single species of marine tunicate, Clavelina moluccensis. The
      cytotoxic activities of synthesized lepadiformine hydrochloride salts and their
      synthetic intermediates were evaluated.

PMID- 28488779
TI  - Nociceptor plasticity: A closer look.
AB  - Nociceptors are receptors specifically involved in detecting a tissue damage and
      transducing it in an electrical signal. Nociceptor activation provoked by any
      kind of acute lesion is related to the release of several mediators of
      inflammation, within the framework of a process defined as "peripheral
      sensitization." This results in an exaggerated response to the painful stimulus,
      clinically defined as "primary hyperalgesia." The concept of "neuroplasticity"
      may explain the adaptive mechanisms carried out by the Nervous System in relation
      to a "harmful" damage; also, neuroplasticity mechanisms are also fundamental for
      rehabilitative intervention protocols. Here we review several studies that
      addressed the role of different receptors and ionic channels discovered on
      nociceptor surface and their role in pain perception. The changes in expression,
      distribution, and functioning of receptors and ionic channels are thought to be a
      part of the neuroplasticity property, through which the Nervous System constantly
      adapts to external stimuli. Moreover, some of the reviewed mediators are also
      been associated to "central sensitization," a process that results in pain
      chronicization when the painful stimulation is particularly prolonged or intense,
      and lastly leads to the memorization of the uncomfortable painful perception.

PMID- 28488780
TI  - Electrostatic Design of 3D Covalent Organic Networks.
AB  - An innovative strategy for electrostatically designing the electronic structure
      of 3D bulk materials is proposed to control charge carriers at the nanoscale.
      This is achieved by shifting the electronic levels of chemically identical
      semiconducting elements through the periodic arrangement of polar functional
      groups. For the example of covalent organic networks, by first-principles
      calculations, the resulting collective electrostatic effects are shown to allow a
      targeted manipulation of the electronic landscape such that spatially confined
      pathways for electrons and holes can be realized. Mimicking donor-acceptor bulk
      heterojunctions, the new materials hold high promise for photovoltaic
      applications. The distinct advantage over the conventional approach of splitting
      excitons through chemically distinct donor and acceptor units is that here the
      magnitude of the band offset can be continuously tuned by varying the dipole
      density. A particularly promising feature of the suggested strategy is its
      structural versatility, which also enables the realization of more complex
      quantum structures such as quantum-cascades and quantum-checkerboards.

PMID- 28488781
TI  - Deciphering the effects of disperser assemblages and seed mass on patterns of
      seed dispersal in a rodent community.
AB  - The sizes of both seed dispersers and seeds are traits that are likely to
      interact to influence seed fate in many synzoochoric plant species. Here, we
      examined whether members of a granivorous rodent community consisting of species
      of different body size vary in their effectiveness as seed dispersers, and how
      this relationship may be altered by seed size. We marked northern red oak
      (Quercus rubra) acorns with plastic tags and placed them in size-selective rodent
      exclosures. The exclosures allowed differential access of rodent groups based on
      different body size: (i) small (e.g. Peromyscus spp.); (ii) small and medium
      (e.g. Tamias striatus); and (iii) small, medium and large (e.g. Sciurus
      carolinensis) species of rodents. Acorn removal did not differ among exclosure
      types, but more seeds were missing when removed by small rodents, probably
      because of larderhoarding. The treatments did not influence the relative
      frequency of acorn consumption. However, small rodents cached considerably fewer
      and partially ate more acorns than the other 2 groups. The mean dispersal
      distance was the longest for cages with medium openings, intermediate for cages
      with large openings and the shortest for cages with small openings. Acorn mass
      positively affected the probability of caching and this relationship was
      unaffected by exclosure type. In conclusion, granivorous rodents of different
      body sizes strongly differed in their interactions with acorns, with small
      rodents acting primarily as acorn predators and medium and large species
      contributing significantly more to dispersal of red oaks.

PMID- 28488782
TI  - Survivorship care plans in Spain: A need that cannot be postponed.
AB  - In Spain, as around the world, the number of cancer survivors is increasing.
      There were an estimated 500,000 cancer survivors in 2010. In spite of recognition
      that Survivorship Care Plans (SCPs) are needed, their implementation in Spain has
      been slower than in other countries and only in very recent years some small
      initiatives have been carried out. This editorial addresses the difficulties to
      implement SCPs in the Spanish Health Services and which are the opportunities
      that favour a scenario in which PCPs and oncologists can offer a real patient
      centred care to cancer survivors.

PMID- 28488783
TI  - Light adaptation and the evolution of vertebrate photoreceptors.
AB  - KEY POINTS: Lamprey are cyclostomes, a group of vertebrates that diverged from
      lines leading to jawed vertebrates (including mammals) in the late Cambrian, 500
      million years ago. It may therefore be possible to infer properties of
      photoreceptors in early vertebrate progenitors by comparing lamprey to other
      vertebrates. We show that lamprey rods and cones respond to light much like rods
      and cones in amphibians and mammals. They operate over a similar range of light
      intensities and adapt to backgrounds and bleaches nearly identically. These
      correspondences are pervasive and detailed; they argue for the presence of rods
      and cones very early in the evolution of vertebrates with properties much like
      those of rods and cones in existing vertebrate species. ABSTRACT: The earliest
      vertebrates were agnathans - fish-like organisms without jaws, which first
      appeared near the end of the Cambrian radiation. One group of agnathans became
      cyclostomes, which include lamprey and hagfish. Other agnathans gave rise to
      jawed vertebrates or gnathostomes, the group including all other existing
      vertebrate species. Because cyclostomes diverged from other vertebrates 500
      million years ago, it may be possible to infer some of the properties of the
      retina of early vertebrate progenitors by comparing lamprey to other vertebrates.
      We have previously shown that rods and cones in lamprey respond to light much
      like photoreceptors in other vertebrates and have a similar sensitivity. We now
      show that these affinities are even closer. Both rods and cones adapt to
      background light and to bleaches in a manner almost identical to other vertebrate
      photoreceptors. The operating range in darkness is nearly the same in lamprey and
      in amphibian or mammalian rods and cones; moreover background light shifts
      response-intensity curves downward and to the right over a similar range of
      ambient intensities. Rods show increment saturation at about the same intensity
      as mammalian rods, and cones never saturate. Bleaches decrease sensitivity in
      part by loss of quantum catch and in part by opsin activation of transduction.
      These correspondences are so numerous and pervasive that they are unlikely to
      result from convergent evolution but argue instead that early vertebrate
      progenitors of both cyclostomes and mammals had photoreceptors much like our own.

PMID- 28488784
TI  - CT-determined pulmonary artery to aorta ratio as a predictor of elevated
      pulmonary artery pressure and survival in idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Elevated mean pulmonary artery pressure (mPAP) is a
      significant prognostic indicator in idiopathic pulmonary fibrosis (IPF). It has
      been reported that the computed tomography-determined ratio of the diameter of
      the pulmonary artery to the aorta (PA:A) is correlated with mPAP in various
      respiratory diseases. However, in patients with IPF, whether the PA:A can be used
      to predict elevated mPAP and the prognostic value of the PA:A has not been fully
      evaluated. METHODS: We conducted a single-centre, observational study of 177
      consecutive IPF patients who underwent right heart catheterization. We examined
      the association between the PA:A and mPAP in these patients, and performed a
      receiver operating characteristic (ROC) analysis to test the diagnostic accuracy
      of the PA:A in predicting mPAP > 20 mm Hg (pulmonary hypertension (PH) or
      borderline PH) in relation to survival. RESULTS: In a multivariate linear
      regression analysis, the PA:A, 6-min walk distance and diffusion capacity for
      carbon monoxide (DLCO ) % predicted were independent explanatory variables of
      elevated mPAP (P < 0.0001, P = 0.009 and P = 0.002, respectively). ROC analysis
      revealed a PA:A > 0.9 to be optimal for predicting mPAP > 20 mmHg (area under the
      curve (AUC) = 0.75; 95% CI: 0.65-0.84). Patients with a PA:A > 0.9 also had a
      worse prognosis (P = 0.009). CONCLUSION: Measurement of the PA:A is a useful and
      convenient method to predict elevated mPAP in IPF at initial evaluation.
      Moreover, a PA:A >0.9 was found to be an indicator of worse prognosis.

PMID- 28488785
TI  - Is it acceptable to use coagulation plasma samples stored at room temperature and
      4 degrees C for 24 hours for additional prothrombin time, activated partial
      thromboplastin time, fibrinogen, antithrombin, and D-dimer testing?
AB  - INTRODUCTION: Coagulation laboratories are faced on daily basis with requests for
      additional testing in already analyzed fresh plasma samples. This prompted us to
      examine whether plasma samples stored at room temperature (RT), and 4 degrees C
      for 24 hours can be accepted for additional prothrombin time (PT), activated
      partial thromboplastin time (aPTT), fibrinogen (Fbg), antithrombin (AT), and D
      dimer testing. METHODS: We measured PT, aPTT, Fbg in 50 and AT in 30 plasma
      samples with normal and pathological values, within 4 hours of blood collection
      (baseline results) and after 24-hours storage at RT (primary tubes), and 4
      degrees C (aliquots). D-dimer stability was investigated in 20 samples stored in
      primary tubes at 4 degrees C. RESULTS: No statistically significant difference
      between baseline results and results in samples stored at RT and 4 degrees C was
      observed for PT (P=.938), aPTT (P=.186), Fbg (P=.962), AT (P=.713), and D-dimers
      (P=.169). The highest median percentage changes were found for aPTT, being more
      pronounced for samples stored at 4 degrees C (13.0%) than at RT (8.7%).
      CONCLUSION: Plasma samples stored both at RT and 4 degrees C for 24 hours are
      acceptable for additional PT, Fbg, and AT testing. Plasma samples stored 24 hours
      in primary tubes at 4 degrees C are suitable for D-dimer testing.

PMID- 28488786
TI  - Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of beta
      catenin and hepatocyte nuclear factor 4alpha in hepatocellular carcinoma.
AB  - AIM: The aim of this study is to clarify the correlation of the co-activation of
      beta-catenin and hepatocyte nuclear factor (HNF)4alpha with the findings of
      gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion
      transporting polypeptide (OATP)1B3 expression, and histological findings in
      hepatocellular carcinoma (HCC). METHODS: One hundred and ninety-six HCCs
      surgically resected from 174 patients were enrolled in this study. The HCCs were
      classified into four groups by immunohistochemical expression of beta-catenin,
      glutamine synthetase (GS), and HNF4alpha: (i) beta-catenin/GS (positive [+])
      HNF4alpha (+); (ii) beta-catenin/GS (+) HNF4alpha (negative [-]); (iii) beta
      catenin/GS (-) HNF4alpha (+); and (iv) beta-catenin/GS (-) HNF4alpha (-). We
      compared the four groups in terms of the enhancement ratio on the hepatobiliary
      phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion
      transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid)
      expression and histological features, overall survival, and no recurrence
      survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test,
      Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical
      analyses. RESULTS: Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with
      beta-catenin/GS (+) HNF4alpha (+) was significantly higher than those of the
      other three groups (P < 0.001). The OATP1B3 grade was also significantly higher
      in HCC with beta-catenin/GS (+) HNF4alpha (+) (P < 0.001). Hepatocellular
      carcinoma with beta-catenin/GS (+) HNF4alpha (+) showed the highest
      differentiation grade as compared to the other groups (P < 0.004). There were no
      significant differences in portal vein invasion, macroscopic growth pattern, or
      prognosis analyses between the four groups. CONCLUSION: Co-activation of beta
      catenin and HNF4alpha would promote OATP1B3 expression, and consequently higher
      enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade
      in HCC.

PMID- 28488787
TI  - Nitrotoga is selected over Nitrospira in newly assembled biofilm communities from
      a tap water source community at increased nitrite loading.
AB  - Community assembly is a central topic in microbial ecology: how do assembly
      processes interact and what is the relative contribution of stochasticity and
      determinism? Here, we exposed replicate flow-through biofilm systems, fed with
      nitrite-supplemented tap water, to continuous immigration from a source
      community, present in the tap water, to determine the extent of selection and
      neutral processes in newly assembled biofilm communities at both the community
      and the functional guild (of nitrite-oxidizing bacteria, NOB) levels. The
      community composition of biofilms assembled under low and high nitrite loading
      was described after 40 days of complete nitrite removal. The total community
      assembly, as well as the NOB guild assembly were largely governed by a
      combination of deterministic and stochastic processes. Furthermore, we observed
      deterministic enrichment of certain types of NOB in the biofilms. Specifically,
      elevated nitrite loading selected for a single Nitrotoga representative, while
      lower nitrite conditions selected for a number of Nitrospira. Therefore, even
      when focusing on ecologically coherent ensembles, assembly is the result of
      complex stochastic and deterministic processes that can only be interrogated by
      observing multiple assemblies under controlled conditions.

PMID- 28488788
TI  - Solvent-Free Self-Assembly to the Synthesis of Nitrogen-Doped Ordered Mesoporous
      Polymers for Highly Selective Capture and Conversion of CO2.
AB  - A solvent-free induced self-assembly technology for the synthesis of nitrogen
      doped ordered mesoporous polymers (N-OMPs) is developed, which is realized by
      mixing polymer precursors with block copolymer templates, curing at 140-180 
      degrees C, and calcination to remove the templates. This synthetic strategy
      represents a significant advancement in the preparation of functional porous
      polymers through a fast and scalable yet environmentally friendly route, since no
      solvents or catalysts are used. The synthesized N-OMPs and their derived
      catalysts are found to exhibit competitive CO2 capacities (0.67-0.91 mmol g-1 at
      25  degrees C and 0.15 bar), extraordinary CO2 /N2 selectivities (98-205 at 25 
      degrees C), and excellent activities for catalyzing conversion of CO2 into cyclic
      carbonate (conversion >95% at 100  degrees C and 1.2 MPa for 1.5 h). The solvent
      free technology developed in this work can also be extended to the synthesis of N
      OMP/SiO2 nanocomposites, mesoporous SiO2 , crystalline mesoporous TiO2 , and
      TiPO, demonstrating its wide applicability in porous material synthesis.

PMID- 28488789
TI  - Iron-Catalyzed Intermolecular 1,2-Difunctionalization of Styrenes and Conjugated
      Alkenes with Silanes and Nucleophiles.
AB  - The first iron-catalyzed 1,2-difunctionalization of styrenes and conjugated
      alkenes with silanes and either N or C, using an oxidative radical strategy, is
      described. Employing FeCl2 and di-tert-butyl peroxide allows divergent alkene 1,2
      difunctionalizations, including 1,2-aminosilylation, 1,2-arylsilylation, and 1,2
      alkylsilylation, which rely on a wide range of nucleophiles, namely, amines,
      amides, indoles, pyrroles, and 1,3-dicarbonyls, thus providing a powerful
      platform for producing diverse silicon-containing alkanes.

PMID- 28488790
TI  - Pseudohalide-Exchanged Quantum Dot Solids Achieve Record Quantum Efficiency in
      Infrared Photovoltaics.
AB  - Application of pseudohalogens in colloidal quantum dot (CQD) solar-cell active
      layers increases the solar-cell performance by reducing the trap densities and
      implementing thick CQD films. Pseudohalogens are polyatomic analogs of halogens,
      whose chemistry allows them to substitute halogen atoms by strong chemical
      interactions with the CQD surfaces. The pseudohalide thiocyanate anion is used to
      achieve a hybrid surface passivation. A fourfold reduced trap state density than
      in a control is observed by using a suite of field-effect transistor studies.
      This translates directly into the thickest CQD active layer ever reported,
      enabled by enhanced transport lengths in this new class of materials, and leads
      to the highest external quantum efficiency, 80% at the excitonic peak, compared
      with previous reports of CQD solar cells.

PMID- 28488791
TI  - Assessment of semi-quantitative grading of red blood cell abnormalities utilizing
      images from the CellaVision DM96 compared to manual light microscopy.

PMID- 28488792
TI  - Comprehensive database of Manufactured Gas Plant tars. Part A. Database.
AB  - RATIONALE: Coal tars are a mixture of organic and inorganic compounds that were
      by-products from the manufactured gas and coke making industries. Different
      manufacturing processes have resulted in the production of distinctly different
      tar compositions. This study presents a comprehensive database of compounds
      produced using two-dimensional gas chromatography combined with time-of-flight
      mass spectrometry (GCxGC/TOFMS), analysing 16 tar samples produced by five
      distinct production processes. METHODS: Samples of coal tar were extracted using
      accelerated solvent extraction (ASE) and derivatised post-extraction using N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane
      (TMCS). The derivatised samples were analysed using two-dimensional gas
      chromatography combined with time-of-flight mass spectrometry (GCxGC/TOFMS).
      RESULTS: A total of 16 tar samples originating from five different production
      processes: Low Temperature Horizontal Retorts, Horizontal Retorts, Vertical
      Retorts, Carbureted Water Gas and Coke Ovens, were analysed. A total of 2369
      unique compounds were detected with 948 aromatic compounds, 196 aliphatic
      compounds, 380 sulfur-containing compounds, 209 oxygen-containing compounds, 262
      nitrogen-containing compounds and 15 mixed heterocycles. Derivatisation allowed
      the detection of 359 unique compounds, the majority in the form of hydroxylated
      polycyclic aromatic hydrocarbons, many of which would not have been detected
      without derivatisation. Of the 2369 unique compounds detected, 173 were found to
      be present within all samples. CONCLUSIONS: A unique comprehensive database of
      compounds detected within 16 tar samples from five different production processes
      was produced. The 173 compounds identified within every sample may be of
      particular importance from a regulatory standpoint. This initial study indicates
      that different production processes produce tars with different chemical
      signatures and it can be further expanded upon by in-depth analysis of the
      different compound types. The number of compounds presented within this database
      clearly demonstrates the analytical power of GCxGC/TOFMS.

PMID- 28488793
TI  - Atomic force microscopy studies of bioprocess engineering surfaces - imaging,
      interactions and mechanical properties mediating bacterial adhesion.
AB  - The detrimental effect of bacterial biofilms on process engineering surfaces is
      well documented. Thus, interest in the early stages of bacterial biofilm
      formation; in particular bacterial adhesion and the production of anti-fouling
      coatings has grown exponentially as a field. During this time, Atomic force
      microscopy (AFM) has emerged as a critical tool for the evaluation of bacterial
      adhesion. Due to its versatility AFM offers not only insight into the
      topographical landscape and mechanical properties of the engineering surfaces,
      but elucidates, through direct quantification the topographical and biomechnical
      properties of the foulants The aim of this review is to collate the current
      research on bacterial adhesion, both theoretical and practical, and outline how
      AFM as a technique is uniquely equipped to provide further insight into the
      nanoscale world at the bioprocess engineering surface.

PMID- 28488794
TI  - Apoptotic Activity of Lactobacillus plantarum DGK-17-Fermented Soybean Seed
      Extract in Human Colon Cancer Cells via ROS-JNK Signaling Pathway.
AB  - Fermented food has been always possesses upper hand compared to normal food due
      to its antibacterial, antioxidant, and anticancer properties. Soybeans, which
      have high nutritional value, are widely consumed in Korea. In this study, soybean
      seed powder fermented with Lactobacillus plantarum DGK-17, which was previously
      isolated from kimchi, showed anticancer potential. Fermented soybean extract
      (FSE) resulted in morphological changes, reduction of cancer cell colony
      formation and apoptotic cell death of HCT-116 colon cancer cells in a dose
      dependent manner, and IC50 value of 111 MUg. FSE treatment caused reduction of
      cell growth in a dose-dependent manner via release of lactate dehydrogenase. FSE
      treatment induced HCT-116 apoptotic cell death as confirmed by the presence of
      fragmented nuclei, oxidative burst, and reduced mitochondrial membrane potential
      (DeltaPsim ). Further, FSE treatment sensitized cells to ER stress via IRE1-alpha
      induction. FSE treatment also resulted in JNK activation, subsequently causing
      activation of Bax and downregulation of BCl2. Weakened mitochondrial membrane
      potential (DeltaPsim ) also caused release of Cyto C, further activating caspase
      mediated cell death. Therefore, this study reveals the apoptotic role of DGK-17
      fermented soybean seed extract in human colon cancer HCT-116 cells.

PMID- 28488795
TI  - The novel bacterial phylum Calditrichaeota is diverse, widespread and abundant in
      marine sediments and has the capacity to degrade detrital proteins.
AB  - Calditrichaeota is a recently recognized bacterial phylum with three cultured
      representatives, isolated from hydrothermal vents. Here we expand the phylogeny
      and ecology of this novel phylum with metagenome-derived and single-cell genomes
      from six uncultivated bacteria previously not recognized as members of
      Calditrichaeota. Using 16S rRNA gene sequences from these genomes, we then
      identified 322 16S rRNA gene sequences from cultivation-independent studies that
      can now be classified as Calditrichaeota for the first time. This dataset was
      used to re-analyse a collection of 16S rRNA gene amplicon datasets from marine
      sediments showing that the Calditrichaeota are globally distributed in the seabed
      at high abundance, making up to 6.7% of the total bacterial community. This wide
      distribution and high abundance of Calditrichaeota in cold marine sediment has
      gone unrecognized until now. All Calditrichaeota genomes show indications of a
      chemoorganoheterotrophic metabolism with the potential to degrade detrital
      proteins through the use of extracellular peptidases. Most of the genomes contain
      genes encoding proteins that confer O2 tolerance, consistent with the relatively
      high abundance of Calditrichaeota in surficial bioturbated part of the seabed
      and, together with the genes encoding extracellular peptidases, suggestive of a
      general ecophysiological niche for this newly recognized phylum in marine
      sediment.

PMID- 28488796
TI  - Will the safe-breakers of sleep apnoea find the right combination?

PMID- 28488797
TI  - Conformational flexibility in the RNA stem-loop structures formed by CAG repeats.
AB  - The expansion of CAG repeats has been found to be associated with at least nine
      human genetic disorders. In these disorders, the full-length expanded CAG RNA
      transcripts are cleaved into small CAG-repeated RNAs which are cytotoxic and
      known to be capable of forming hairpins. To better understand the RNA pathogenic
      mechanism, in this study we have performed high-resolution nuclear magnetic
      resonance structural investigations on the RNA hairpins formed by CAG repeats.
      Our results show the formation of a type III AGCA tetraloop and reveal the effect
      of stem rigidity on the loop conformational flexibility.

PMID- 28488798
TI  - A comparison of sedimentary DNA and pollen from lake sediments in recording
      vegetation composition at the Siberian treeline.
AB  - Reliable information on past and present vegetation is important to project
      future changes, especially for rapidly transitioning areas such as the boreal
      treeline. To study past vegetation, pollen analysis is common, while current
      vegetation is usually assessed by field surveys. Application of detailed
      sedimentary DNA (sedDNA) records has the potential to enhance our understanding
      of vegetation changes, but studies systematically investigating the power of this
      proxy are rare to date. This study compares sedDNA metabarcoding and pollen
      records from surface sediments of 31 lakes along a north-south gradient of
      increasing forest cover in northern Siberia (Taymyr peninsula) with data from
      field surveys in the surroundings of the lakes. sedDNA metabarcoding recorded 114
      plant taxa, about half of them to species level, while pollen analyses identified
      43 taxa, both exceeding the 31 taxa found by vegetation field surveys. Increasing
      Larix percentages from north to south were consistently recorded by all three
      methods and principal component analyses based on percentage data of vegetation
      surveys and DNA sequences separated tundra from forested sites. Comparisons of
      the ordinations using procrustes and protest analyses show a significant fit
      among all compared pairs of records. Despite similarities of sedDNA and pollen
      records, certain idiosyncrasies, such as high percentages of Alnus and Betula in
      all pollen and high percentages of Salix in all sedDNA spectra, are observable.
      Our results from the tundra to single-tree tundra transition zone show that
      sedDNA analyses perform better than pollen in recording site-specific richness
      (i.e., presence/absence of taxa in the vicinity of the lake) and perform as well
      as pollen in tracing vegetation composition.

PMID- 28488799
TI  - Systematic review of exercise training in colorectal cancer patients during
      treatment.
AB  - Colorectal cancer surgery results in considerable postoperative morbidity,
      mortality and reduced quality of life. As many patients will undergo additional
      (neo)adjuvant therapy, it is imperative that each individual optimize their
      physical function. To elucidate the potential of exercise in patient
      optimization, we investigated the evidence for an exercise program before and
      after surgical treatment in colorectal cancer patients. A systematic review was
      conducted according to the Cochrane Handbook for Systematic Reviews of
      Interventions, the guidelines of the Physical Therapy Journal and the PRISMA
      guidelines. No literature pertaining to exercise training during preoperative
      neoadjuvant treatment was found. Seven studies, investigating the effects of
      regular exercise during adjuvant chemotherapy for patients with colorectal cancer
      or a mixed population, were identified. A small effect (effect size (ES) 0.4) of
      endurance/interval training and strength training (ES 0.4) was found in two
      studies conducted in patients with colorectal and gastrointestinal cancer. In
      five studies that included a mixed population of cancer patients, interval
      training resulted in a large improvement (ES 1.5; P<=.05). Endurance training
      alone was found to increase both lower extremity strength and endurance capacity.
      The effects of strength training in the lower extremity are moderate, whereas, in
      the upper extremity, the increase is small. There is limited evidence available
      on exercise training during treatment in colorectal cancer patients. One study
      concluded exercise therapy may be beneficial for colorectal cancer patients
      during adjuvant treatment. The possible advantages of training during neoadjuvant
      treatment may be explored by prehabilitation trials.

PMID- 28488800
TI  - Relevance of ethnic differences in factor XIII activity on laboratory reference
      ranges.

PMID- 28488801
TI  - Measuring and achieving the best possible outcomes in surgery.

PMID- 28488802
TI  - Profound spherocytosis in adulthood: Acquired, hereditary or both?

PMID- 28488803
TI  - Promises and Challenges in Continuous Tracking Utilizing Amino Acids in Skin
      Secretions for Active Multi-Factor Biometric Authentication for Cybersecurity.
AB  - We consider a new concept of biometric-based cybersecurity systems for active
      authentication by continuous tracking, which utilizes biochemical processing of
      metabolites present in skin secretions. Skin secretions contain a large number of
      metabolites and small molecules that can be targeted for analysis. Here we argue
      that amino acids found in sweat can be exploited for the establishment of an
      amino acid profile capable of identifying an individual user of a mobile or
      wearable device. Individual and combinations of amino acids processed by
      biocatalytic cascades yield physical (optical or electronic) signals, providing a
      time-series of several outputs that, in their entirety, should suffice to
      authenticate a specific user based on standard statistical criteria. Initial
      results, motivated by biometrics, indicate that single amino acid levels can
      provide analog signals that vary according to the individual donor, albeit with
      limited resolution versus noise. However, some such assays offer digital
      separation (into well-defined ranges of values) according to groups such as age,
      biological sex, race, and physiological state of the individual. Multi-input
      biocatalytic cascades that handle several amino acid signals to yield a single
      digital-type output, as well as continuous-tracking time-series data rather than
      a single-instance sample, should enable active authentication at the level of an
      individual.

PMID- 28488805
TI  - Breastfeeding Considerations for Mothers of Infants with Neonatal Abstinence
      Syndrome.
AB  - Breastfeeding offers many benefits to both mother and baby. Breastfeeding is
      generally recommended for mothers of infants with neonatal abstinence syndrome
      (NAS) unless some associated risk outweighs the benefits. Evidence indicates that
      infants with NAS who receive human milk require less pharmacologic treatment and
      have shorter hospital lengths of stay. Perhaps the greatest barrier to
      breastfeeding for women with opioid dependence is the inaccurate and inconsistent
      information they receive from different sources, including health care
      professionals. The American Congress of Obstetricians and Gynecologists, American
      Academy of Pediatrics, and Academy of Breastfeeding Medicine (ABM) have published
      statements that support breastfeeding infants with NAS. The ABM has a dedicated
      protocol to guide clinicians in deciding which mothers should and which mothers
      should not breastfeed their infants. In this review, studies evaluating the
      effects of breastfeeding, professional organizations' protocols and
      recommendations regarding breastfeeding, and barriers to breastfeeding infants
      with NAS are discussed, as well as the dangers of illicit drug exposure and
      avoiding rebound NAS in a breastfed infant. Clinicians can play an important role
      in in identifying, supporting, counseling, and advocating for mothers who wish to
      breastfeed their infant with NAS.

PMID- 28488804
TI  - Three-Dimensional Shape and Surface Features Distinguish Multiple Sclerosis
      Lesions from Nonspecific White Matter Disease.
AB  - BACKGROUND AND PURPOSE: There remains a need to further refine the ability of
      clinicians to differentiate multiple sclerosis (MS) from other disease
      etiologies. Here, we illustrate the value of 3-dimensional (3D) geometric shape
      and surface lesion characteristics between disease states. METHODS: Standardized
      3-Tesla 3D brain magnetic resonance imaging studies were performed on enrolled MS
      and nonspecific white matter (NSWM) patients. Focal supratentorial lesions were
      identified, reconstructed using maximum intensity projection, manually segmented,
      and 3D printed. Printed 3D models were randomly evaluated by three blinded raters
      for selected shape and surface characteristics. Regression models adjusting for
      age, disease duration, and individual patient effects were applied to assess
      lesion characteristics between patient groups. Patient-level and latent class
      analyses between groups were performed. RESULTS: A total of 1,001 supratentorial
      lesions were analyzed (710 MS; 291 NSWM) from 30 patients (19 with confirmed MS
      [11 female; median age = 33.6 years, range: 26.9-54.5], median disease duration =
      2.2 years [.4-19.4]), 11 with verified nonspecific white matter (NSWM) disease
      without MS (11 female; median age = 55.0 years, range: 27.9-66.2). Lesions
      originating from MS in comparison to NSWM patients demonstrated a higher
      percentage of asymmetry (75.9% vs. 43%; OR: 4.39 [2.37-8.12]; P < .001), complex
      surface morphologies (65.9% vs. 27.8%; OR: 2.3 [1.74-3.05]; P < .001), and were
      multilobular (11.0% vs. .3%, P < .001), and elongated (12.8% vs. 2.4%, P < .001)
      in shape. Spatially, these traits were of higher frequency within the
      juxtacortical, deep white matter, and periventricular regions. CONCLUSION: Three
      dimensional lesion data may provide new biologic insights related to injury along
      with offering another approach for determining the origin of lesion types.

PMID- 28488806
TI  - Knowledge Management in healthcare libraries: the current picture.
AB  - Knowledge management has seen something of a resurgence in attention amongst
      health librarians recently. Of course it has never ceased to exist, but now many
      library staff are becoming more involved in organisational knowledge management,
      and positioning themselves as key players in the sphere. No single model of
      knowledge management is proliferating, but approaches that best fit the
      organisation's size, structure and culture, and a blending of evidence based
      practice and knowledge sharing. Whatever it is called and whatever models are
      used, it's clear that for librarians and information professionals, the
      importance of putting knowledge and evidence into practice, sharing knowledge
      well and capturing it effectively, are still what we will continue to do.

PMID- 28488807
TI  - The information needs of occupational therapy students: a case study.
AB  - This article summarises a case study on the information needs of Masters level
      Occupational Therapy 5 (OT) students at one English university. A mixed methods
      questionnaire was used to explore motivators for information-seeking, preferred
      information resources and barriers inhibiting the satisfaction of information
      needs. Thirteen recommendations for practice were formulated, focusing on how
      information professionals can best facilitate OT students' learning and evidence
      based research skills in preparation for clinical practice. The study was
      completed by Jane Morgan-Daniel, who received a Distinction for her work from
      Aberystwyth University, where she graduated with an MSC in Information and
      Library Studies in December 2016. She has written this article together with her
      dissertation supervisor, Hugh Preston. A. M.

PMID- 28488808
TI  - Cracking induction in health libraries: is there a right way?
AB  - In most instances, inductions are the first time that users will be introduced to
      health library services. The time available in which to deliver library
      orientation sessions within a broader, Trust induction programme is often
      limited, and this can present challenges for health librarians. Inductions are a
      great marketing tool, and it is important that induction sessions make the right
      impact. Within a brief window of opportunity, the health librarian must impart
      key information to the inductees whilst ensuring the session is relevant and
      memorable. In this article, guest writer Nicola Healey, Library Manager of North
      Somerset Healthcare Library, discusses the range of approaches she and her
      colleagues have explored in delivering library inductions, explaining what
      worked, what did not and what areas still remain for development. H. S.

PMID- 28488809
TI  - Optimized isolation and expansion of human airway epithelial basal cells from
      endobronchial biopsy samples.
AB  - Autologous airway epithelial cells have been used in clinical tissue-engineered
      airway transplantation procedures with a view to assisting mucosal regeneration
      and restoring mucociliary escalator function. However, limited time is available
      for epithelial cell expansion due to the urgent nature of these interventions and
      slow epithelial regeneration has been observed in patients. Human airway
      epithelial cells can be expanded from small biopsies or brushings taken during
      bronchoscopy procedures, but the optimal mode of tissue acquisition from patients
      has not been investigated. Here, we compared endobronchial brushing and
      endobronchial biopsy samples in terms of their cell number and their ability to
      initiate basal epithelial stem cell cultures. We found that direct co-culture of
      samples with 3T3-J2 feeder cells in culture medium containing a Rho-associated
      protein kinase inhibitor, Y-27632, led to the selective expansion of greater
      numbers of basal epithelial stem cells during the critical early stages of
      culture than traditional techniques. Additionally, we established the benefit of
      initiating cell cultures from cell suspensions, either using brushing samples or
      through enzymatic digestion of biopsies, over explant culture. Primary epithelial
      cell cultures were initiated from endobronchial biopsy samples that had been
      cryopreserved before the initiation of cell cultures, suggesting that
      cryopreservation could eliminate the requirement for close proximity between the
      clinical facility in which biopsy samples are taken and the specialist laboratory
      in which epithelial cells are cultured. Overall, our results suggest ways to
      expedite epithelial cell preparation in future airway cell therapy or
      bioengineered airway transplantation procedures.

PMID- 28488810
TI  - One gene, multiple alleles: insights into the microevolution of pigmentation
      polymorphisms.
AB  - Understanding how phenotypic variation is generated and maintained, and the
      evolutionary forces that shape these processes is the main goal of evolutionary
      biology. Great progress has been made in uncovering the genetic basis of
      morphological diversity, yet little is known about both the genetics and
      developmental basis of discrete polymorphisms segregating in wild populations.
      Exploring variation in developmental mechanisms at the population level can
      address the long-standing question of whether the mechanisms of change are the
      same at the micro- and macroevolutionary scale. This integration has been
      difficult mainly because the study of the evolution of developmental mechanisms
      and population genetics remain separate (Genetics, 195, 625 and 2013). In this
      issue of Molecular Ecology, Roberts et al. (Molecular Ecology and 2017) make a
      significant contribution towards bridging this gap by studying the genetic and
      developmental basis of an extremely variable pigmentation pattern. A polymorphic
      blotched coloration is common among females of four genera of Lake Malawi
      cichlids. The presence of this phenotype associates with a noncoding SNP upstream
      of the transcription factor pax7a (Science, 326, 998 and 2009). The authors
      describe in detail the morphs' pigmentation development, showing that phenotypic
      differences result from alterations in pigment cell development and survival.
      Next, using controlled crosses and population genetics studies, they identified
      three putative pax7a dominant blotch alleles that are associated with specific
      morphs. These different alleles lead to higher levels of pax7a transcript that
      correlate with different pigment cell composition. Finally, sequence comparison
      of the locus within populations and between species revealed a common origin of
      the allele controlling the blotched morph followed by a pattern of sequential
      appearance of derived alleles that gave rise to morph diversity. The coupling of
      the evolutionary history of this allelic series with the developmental analysis
      of the phenotype paves the way for a mechanistic understanding of morphological
      innovation and diversification.

PMID- 28488811
TI  - Resolution of Occlusive Carotid Artery Thrombus Treated with Anticoagulation as
      Demonstrated on Duplex Ultrasonography.
AB  - BACKGROUND AND PURPOSE: While the majority of cerebral ischemic events due to
      carotid occlusive disease result from atherosclerotic plaque rupture,
      intraluminal carotid artery thrombus occasionally occurs in patients without
      preexisting carotid atherosclerosis. Identification of nonatherosclerotic
      thrombus as the cause of the carotid occlusive disease can obviate the need for
      an interventional procedure, and resolution of thrombus can be monitored with B
      mode duplex ultrasonography. METHODS: We reviewed 3 patients treated on The Mount
      Sinai Hospital Stroke Unit with anticoagulation for nonatherosclerotic carotid
      thrombi and followed with serial Doppler ultrasonogrpahy for resolution of
      thrombus. RESULTS: Occlusive carotid thrombus was successfully treated in all 3
      patients with systemic anticoagulation. B-mode duplex ultrasonography allowed for
      demonstration of resolving thrombus. CONCLUSION: Differentiation between a
      stenotic plaque and occlusive thrombus can be achieved by ultrasonographic
      analysis of thrombus morphology, attachment site potential, and characteristics
      of a resolving thrombus. Systemic anticoagulation can safely and effectively
      eliminate the risk for future embolization and complete occlusion of the carotid
      artery in patients who present with transient ischemic events or completed
      infarcts of small size.

PMID- 28488812
TI  - Decreased body mass index is associated with impaired survival in lung cancer
      patients with brain metastases: A retrospective analysis of 624 patients.
AB  - Body mass index (BMI) is a prognostic factor in several cancer types. We
      investigated the prognostic role of BMI in a large patient cohort with newly
      diagnosed lung cancer brain metastases (BM) between 1990 and 2013. BMI at
      diagnosis of BM and graded prognostic assessment (GPA) were calculated.
      Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50
      24.99) and overweight (BMI >= 25.00). A total of 624 patients (men 401/624
      [64.3%]; women 223/624 [35.7%]; median age of 61 [range 33-88]) were analysed.
      Histology was non-small cell lung cancer in 417/622 (66.8%), small cell lung
      cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%)
      patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight
      and 39/624 (6.3%) were underweight. Underweight patients had shorter median
      overall survival (3 months) compared to patients with normal BMI (7 months) and
      overweight (8 months; p < .001; log rank test). At multivariate analysis, higher
      GPA class (HR 1.430; 95% cumulative incidence, CI 1.279-1.598; p < .001; Cox
      regression model), SCLC histology (HR 1.310; 95% CI 1.101-1.558) and presence of
      underweight (HR 1.845; 95% CI 1.317-2.585; p = .014; Cox regression model) were
      independent prognostic factors. Underweight at diagnosis of BM in lung cancer is
      associated with an unfavourable prognosis.

PMID- 28488813
TI  - Imaging mass spectrometry for metabolites: technical progress, multimodal
      imaging, and biological interactions.
AB  - Imaging mass spectrometry (IMS) allows the study of the spatial distribution of
      small molecules in biological samples. IMS is able to identify and quantify
      chemicals in situ from whole tissue sections to single cells. Both vacuum mass
      spectrometry (MS) and ambient MS systems have advanced considerably over the last
      decade; however, some limitations are still hard to surmount. Sample
      pretreatment, matrix or solvent choices, and instrument improvement are the key
      factors that determine the successful application of IMS to different samples and
      analytes. IMS with innovative MS analyzers, powerful MS spectrum databases, and
      analysis tools can efficiently dereplicate, identify, and quantify natural
      products. Moreover, multimodal imaging systems and multiple MS-based systems
      provide additional structural, chemical, and morphological information and are
      applied as complementary tools to explore new fields. IMS has been applied to
      reveal interactions between living organisms at molecular level. Recently, IMS
      has helped solve many previously unidentifiable relations between bacteria,
      fungi, plants, animals, and insects. Other significant interactions on the
      chemical level can also be resolved using expanding IMS techniques. WIREs Syst
      Biol Med 2017, 9:e1387. doi: 10.1002/wsbm.1387 For further resources related to
      this article, please visit the WIREs website.

PMID- 28488814
TI  - iPhos-PseEvo: Identifying Human Phosphorylated Proteins by Incorporating
      Evolutionary Information into General PseAAC via Grey System Theory.
AB  - Protein phosphorylation plays a critical role in human body by altering the
      structural conformation of a protein, causing it to become activated/deactivated,
      or functional modification. Given an uncharacterized protein sequence, can we
      predict whether it may be phosphorylated or may not? This is no doubt a very
      meaningful problem for both basic research and drug development. Unfortunately,
      to our best knowledge, so far no high throughput bioinformatics tool whatsoever
      has been developed to address such a very basic but important problem due to its
      extremely complexity and lacking sufficient training data. Here we proposed a
      predictor called iPhos-PseEvo by (1) incorporating the protein sequence
      evolutionary information into the general pseudo amino acid composition (PseAAC)
      via the grey system theory, (2) balancing out the skewed training datasets by the
      asymmetric bootstrap approach, and (3) constructing an ensemble predictor by
      fusing an array of individual random forest classifiers thru a voting system.
      Rigorous jackknife tests have indicated that very promising success rates have
      been achieved by iPhos-PseEvo even for such a difficult problem. A user-friendly
      web-server for iPhos-PseEvo has been established at http://www.jci
      bioinfo.cn/iPhos-PseEvo, by which users can easily obtain their desired results
      without the need to go through the complicated mathematical equations involved.
      It has not escaped our notice that the formulation and approach presented here
      can be used to analyze many other problems in protein science as well.

PMID- 28488816
TI  - Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The
      First TylF Family O-Methyltransferase Works on a 4'-Deoxysugar.
AB  - Sugar O-methylation is a ubiquitous modification in natural products and plays
      diverse roles. This realization has inspired many attempts to search for novel
      methyltransferases. Chalcomycins are a group of 16-membered macrolides containing
      two methylated sugars that require three methyltransferases for their
      biosynthesis. Here, we identified that AlmCII, a sugar O-methyltransferase
      belonging to the TylF family that was previously only known to methylate sugars
      with a 4'-hydroxy group, can methylate a 4',6'-dideoxysugar during the
      biosynthesis of chalcomycins. An in vitro enzymatic assay revealed that AlmCII is
      divalent metal-dependent with an optimal pH of 8.0 and optimal temperature of 42 
      degrees C. Moreover, the 3'-O-demethylated chalcomycins exhibit less than 6 % of
      the antibacterial activity of their parent compounds. This is the first report
      demonstrating that a TylF family O-methyltransferase can use a 4'-deoxy sugar as
      a substrate and highlighting the importance of this methylation for the
      antibacterial activity of chalcomycins.

PMID- 28488815
TI  - Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte
      dendrite elongation.
AB  - The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the
      initial stages of osteocyte differentiation. However, its precise function and
      regulatory mechanisms are still unknown. Due to the known embryonic lethality
      induced by global Pdpn deletion, we have herein explored the effect of bone
      specific Pdpn knockdown on osteocyte form and function in the post-natal mouse.
      Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpnflox/flox
      (cKO) mice and their Pdpnflox/flox controls (fl/fl) has revealed that Pdpn
      deletion significantly compromises tibial cortical bone microarchitecture in both
      sexes, albeit to different extents (p < 0.05). Consistent with this, we observed
      an increase in stiffness in female cKO mice in comparison to fl/fl mice (p <
      0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining
      revealed a significant decrease in the dendrite volume (p < 0.001) and length (p
      < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic
      loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together,
      these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and
      as such, in the control of osteocyte function. As the osteocyte dendritic network
      is known to play vital roles in regulating bone modeling/remodeling, this
      highlights an essential role for Pdpn in bone homeostasis.

PMID- 28488817
TI  - Neladenoson Bialanate Hydrochloride: A Prodrug of a Partial Adenosine A1 Receptor
      Agonist for the Chronic Treatment of Heart Diseases.
AB  - Adenosine is known to be released under a variety of physiological and
      pathophysiological conditions to facilitate the protection and regeneration of
      injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1
      Rs) has been shown to inhibit myocardial pathologies associated with ischemia and
      reperfusion injury, suggesting several options for new cardiovascular therapies.
      When full A1 R agonists are used, the desired protective and regenerative
      cardiovascular effects are usually overshadowed by unintended pharmacological
      effects such as induction of bradycardia, atrioventricular (AV) blocks, and
      sedation. These unwanted effects can be overcome by using partial A1 R agonists.
      Starting from previously reported capadenoson we evaluated options to tailor A1 R
      agonists to a specific partiality range, thereby optimizing the therapeutic
      window. This led to the identification of the potent and selective agonist
      neladenoson, which shows the desired partial response on the A1 R, resulting in
      cardioprotection without sedative effects or cardiac AV blocks. To circumvent
      solubility and formulation issues for neladenoson, a prodrug approach was
      pursued. The dipeptide ester neladenoson bialanate hydrochloride showed
      significantly improved solubility and exposure after oral administration.
      Neladenoson bialanate hydrochloride is currently being evaluated in clinical
      trials for the treatment of heart failure.

PMID- 28488818
TI  - Emerging Global Health Issues: A Nurse's Role

PMID- 28488819
TI  - Simulating Complex Community Disaster Preparedness: Collaboration for Point of
      Distribution

PMID- 28488820
TI  - The Zika Virus Epidemic: Public Health Roles for Nurses

PMID- 28488821
TI  - Prevention and Control of Worldwide Mosquito-Borne Illnesses: Nurses as Teachers

PMID- 28488822
TI  - United States Public Health Service Nurses: Deployment in Global Crisis

PMID- 28488823
TI  - Intra-system reliability of SICS: video-tracking system (Digital.Stadium(r)) for
      performance analysis in soccer.
AB  - BACKGROUND: The correct evaluation of external load parameters is a key factor in
      professional soccer. The instrumentations usually utilised to quantify the
      external load parameters during official matches are video-tracking systems
      (VTS). VTS is a technology that records two-dimensional position data (x and y)
      at high sampling rates (over 25 Hz). The aim of this study was to evaluate the
      intra-system reliability of Digital.Stadium(r) VTS. METHODS: Twenty-eight
      professional male soccer players taking part in the Italian Serie A (age 24+/-6
      years, body mass 79.5+/-7.8 kg, stature 1.83+/-0.05 m) during the 2015/16 season
      were enrolled in this study (team A and team B). Video-analysis was done during
      an official match and data analysis was performed immediately after the game
      ended and then replicated a week later. RESULTS: This study reported a near
      perfect relationship between the initial analysis (analysis 1) and the replicated
      analysis undertaken a week later (analysis 2). R2 coefficients were highly
      significant for each of the performance parameters, P<0.001. This study reported
      a mean TD=8095+/-3271 and 8073+/-3263 m in analysis 1 and analysis 2,
      respectively. Players reported a mean distance covered over 25 w kg-1 equivalent
      to 1304+/-673 m and 1294+/-672 m, and they reported a mean metabolic power of
      9.65+/-1.64 w kg-1 and 9.58+/-1.61 w kg-1, in analysis 1 and analysis 2,
      respectively. CONCLUSIONS: The findings reported in this study underlined that
      all data reported by Digital.Stadium(r) VTS showed high levels of absolute and
      relative reliability.

PMID- 28488824
TI  - Effects of verbal encouragement on force and electromyographic activations during
      exercise.
AB  - BACKGROUND: The aim of the present study was to examine the effects of verbal
      encouragement on isometric force and associated electromyographic (EMG)
      parameters during a handgrip task. METHODS: Twenty-three participants (12 women
      and 11 men) performed maximal voluntary isometric handgrip contractions following
      three conditions: 1) verbal encouragement (VE) condition: participants executed
      isometric contractions while being verbally encouraged; 2) non-verbal
      encouragement (nVE) condition: the same starting and stopping signal but without
      encouragement; 3) non-concentration and non-motivation (nCM) condition: self
      initiated contractions without concentration and motivation. Start and stop of
      the contraction were self-initiated. The maximal voluntary force (MVF) and the
      maximal rate of force development (MRFD) were measured. Integrated EMG
      corresponding to MVF (iEMGMVF) and to MRFD (iEMGMRFD) were collected from flexor
      digitorum superficialis (FDS) and extensor digitorum communis (EDC) muscles.
      RESULTS: MVF was higher during VE compared with nVE (+11.7%; P<0.05) and nCM
      (+23.2%; P<0.05) conditions. Likewise, MRFD was significantly higher during VE,
      compared with nVE (+21.7%; P<0.05) and nCM (+55.4%; P<0.05) conditions. iEMGMVF
      increased for FDS and EDC during VE, compared to nVE (+26.19%, +20.5%) and nCM
      conditions (+68.85%, +48.91%), respectively. iEMGMRFD increased for FDS and EDC
      during VE, compared to nVE (+21.2%, +46.07%) and nCM conditions (+23.79%,
      +42.32%). Furthermore, the reproducibility of all these indices was higher with
      VE condition. CONCLUSIONS: Taken together, force production (MVF and MRFD) and
      EMG data supported the view that muscles activity is considerably influenced by
      the verbal encouragements during isometric force exercise.

PMID- 28488825
TI  - A randomized trial of the effects of an aquatic exercise program on depression,
      anxiety levels, and functional capacity of people who suffered an ischemic
      stroke.
AB  - BACKGROUND: Aquatic exercise programs are used in rehabilitation and might help
      to reduce disability after stroke. This was a randomized intervention trial to
      assess the influence of an aquatic exercise program on people suffering from
      depression and anxiety after ischemic stroke. METHODS: Participants were
      randomized to an experimental group (EG) composed of 19 individuals (51.8+/-8.5
      years; ten males and nine females), and a control group (CG) composed of 17
      people (52.7+/-6.7 years; nine males and eight females). The aquatic exercise
      program consisted of two sessions per week, each lasting between 45 and 60
      minutes and divided into 5 to 10 minutes exercise sections during 12 weeks. The
      State-Trait Anxiety Inventory was used to determine anxiety levels while the Beck
      Depression Inventory was used as a self-assessment of depression. RESULTS: EG
      improved measures of depression, anxiety trait and anxiety state between pre- and
      post-treatment, with no changes in CG. EG improved in all tests related to
      functional capacity compared to CG. CONCLUSIONS: The practice of aquatic
      exercises promotes improvements in the levels of depression and anxiety in people
      who suffered an ischemic stroke.

PMID- 28488826
TI  - Soccer training: high-intensity interval training is mood disturbing while small
      sided games ensure mood balance.
AB  - BACKGROUND: The aim of the study was to compare the effects of high-intensity
      intermittent training (HIIT) versus small-sided games (SSG) in soccer on both the
      physiological responses and the mood state of players. METHODS: Sixteen
      professional soccer players took part in the study (age: 24.1+/-0.9 years).
      Testing of players was conducted on separate days in a randomized and counter
      balanced order (each training session: 28 minutes: 4x4 minutes work with 3
      minutes of passive recovery in-between). Effort: HIIT: intermittent 15-s runs at
      110% maximal aerobic speed with 15 seconds of passive recovery in-between. SSG: 4
      versus 4 players on a 25x35 meter pitch size with full-involvement play.
      Psychological responses before and after each training-session were assessed
      using the profile of mood-state (POMS: Tension, Depression, Anger, Vigor,
      Fatigue, and Confusion). The players' heart rate (HR) was continuously measured,
      whereas ratings of perceived exertion (RPE) and blood lactate concentration
      ([La]) were collected ~3-min after each training-session. RESULTS: HIIT and SSG
      showed no significant difference in HR, RPE and [La] responses. The HIIT compared
      with SSG resulted in: an increased total mood disturbance (P<0.001), tension
      (P<0.05), fatigue (P<0.01) and a decreased vigor (P<0.001). CONCLUSIONS: Both
      HIIT and SSG sessions induced similar physiological responses, in contrast, HIIT
      produced a mood disturbance while SSG ensured mood balance. Practitioners could
      choose between these two exercises according to the objective of their training,
      keeping in mind the mood-related advantages of the SSG shown in the present
      study.

PMID- 28488827
TI  - Water versus land-based exercises as physical training programs in elderly.
AB  - BACKGROUND: The study aims to analyze and quantify the improvements of some
      physical skills in a group of subjects over 65 years old who practice regular
      activities in the gym and in a microgravity environment. METHODS: The study
      included 132 subjects (68.9+/-5.5 years, 72.7+/-14.4 kg, 155.3+/-9.2, 30.6+/-5
      kg/m2) who perform regular physical activity adapted and controlled for the
      elderly twice a week (50' per session) for a period of 8 months. The tests
      evaluate flexibility, abdominal and leg strength and balance. The groups, in
      baseline, are homogeneous between them to anthropometric parameters and the
      initial performance of motor skills analyzed. A mixed between-within subject
      ANOVA was conducted to assess the impact of the training regimens. Data from this
      study showed an increase in muscular strength (leg and abdominal muscles), body
      balance and muscular flexibility after 8 months of both training methods.
      RESULTS: Both experimental groups had significant improvements in motor skills
      considered and interesting results were observed in water activity, overall, in
      balance (+66%, P<0.001) and abdominal muscular strength (+16%, P<0.001) where the
      water group showed a significant within and between improvement. CONCLUSIONS:
      Current results indicate that the water and land programs improved motor skills
      in the elderly. Furthermore, when the effectiveness of the training programs was
      compared, it was verified that the water group has recorded major changes,
      overall on abdominal strength and balance test statistically significant versus
      the land group.

PMID- 28488828
TI  - Effects of active recovery during interval training on plasma catecholamines and
      insulin.
AB  - BACKGROUND? Active recovery has been used as a method to accelerate the recovery
      during intense exercise. It also has been shown to improve performance in
      subsequent exercises, but little is known about its acute effects on the hormonal
      and metabolic profile. The aim of this research was to study the effects of
      active recovery on plasma catecholamines and plasma insulin during a high
      intensity interval exercise. METHODS? Seven subjects performed two high-intensity
      interval training protocols which consisted of three 30-second high-intensity
      bouts (constant intensity), separated by a recovery of 4 minutes. The recovery
      was either active recovery or passive recovery. During the main test blood
      samples were collected and plasma insulin, plasma catecholamines and blood
      lactate were determined. Furthermore, respiratory gasses were also measured.
      RESULTS? Plasma insulin and blood lactate were significantly higher in the
      passive recovery trial, while plasma adrenaline was higher in the active
      recovery. Additionally, VO2 and VCO2 were significantly more increased during the
      active recovery trials. CONCLUSIONS? These results suggest that active recovery
      affects the hormonal and metabolic responses to high-intensity interval exercise.
      Active recovery produces a hormonal environment which may favor lipolysis and
      oxidative metabolism, while passive recovery may be favoring glycolysis.

PMID- 28488829
TI  - Analyzing the relationship between anthropometric and motor indices with
      basketball specific pre-planned and non-planned agility performances.
AB  - BACKGROUND: Although agility is an important quality in basketball, factors
      associated with basketball specific pre-planned-agility (change-of-direction
      speed, CODS) and non-planned-agility (reactive agility, RA) are rarely
      investigated. The aim of this study was to evaluate relationship between
      anthropometric and motor indices with basketball-specific CODS and RA in male
      basketball players of high performance level. METHODS: We tested 88 high-level
      male basketball players (height: 194.62+/-8.09 cm; body mass: 89.13+/-10.81 kg;
      age: 21.12+/-3.47 years). The sample was randomly divided into validation (N.=44)
      and cross-validation (N.=44) subsamples. The study variables included: broad
      jump, countermovement-jump, reactive-strength-index, visual-reaction-time, body
      height, body mass, and body fat percentage (predictors); as well as basketball
      specific CODS and RA (criteria). Univariate associations were assessed by
      Pearson's correlation coefficients. Multivariate relationships between the
      predictors and the criteria were assessed with multiple regression analysis for
      the validation subsample, which was then cross-validated. RESULTS: The
      established multiple regression models were successfully cross-validated for CODS
      (R2=0.40 and 0.36; P=0.01) and RA (R2=0.38 and 0.41; P=0.01, for validation and
      cross-validation subsample, respectively). The broad-jump (i.e., horizontal
      displacement) is important predictor of CODS (Beta=-0.41; P=0.01);
      anthropometrics and body build are specifically associated with RA (Beta=0.51, 
      0.61 and 0.41 for body height, body mass and body fat percentage, respectively;
      all P<0.05), while reactive-strength-index is directly related both to CODS
      (Beta=-0.41, P=0.02), and RA (Beta=-0.40, P=0.03). CONCLUSIONS: While basketball
      players are differentially oriented toward specific game duties, specific
      capacities should be developed in order to meet specific sport requirements.

PMID- 28488830
TI  - Match outcome and sprinting activities in match play by elite German soccer
      players.
AB  - BACKGROUND: The aim of the study was to examine the ways playing positions and
      match outcome (i.e. win, draw, loss) affect the sprint distance covered and the
      number of sprints performed by German Bundesliga soccer players. METHODS: Match
      performance data were collected from 350 soccer players competing in the German
      Bundesliga during the 2014/2015 domestic season. A total of 4393 individual match
      observations were undertaken on outfield players. The analysis was carried using
      the Impire AG motion analysis system with records of all movements of players in
      all the 306 matches. The recorded variables included total sprint distance
      covered and the total number of sprints in offensive and defensive play. The
      conformity assessment was carried out with the Shapiro-Wilk test (P<=0.01). To
      compare mean values of the examined variables a two-way ANOVA was used. The
      differences between pairs of means were verified with Fisher's LSD. RESULTS: The
      analysis of the covered sprint distance and the number of performed sprints
      showed that central defenders and full-backs covered shorter distances in won
      matches than in lost matches (P<=0.05). Furthermore, forwards and wide
      midfielders covered significantly longer sprint distances in won matches than in
      lost matches (P<=0.05). CONCLUSIONS: The match outcome may be viewed as a measure
      of performance accomplishment and, hence, it may influence the sprinting efforts
      made by players.

PMID- 28488831
TI  - Reduced leptin level is independent of fat mass changes and hunger scores from
      high-intensity intermittent plus strength training.
AB  - BACKGROUND: This study aimed to analyze the effects of high-intensity
      intermittent training (HIIT) plus strength training on body composition, hormone
      related to energy balance (leptin), and hunger scores in physically active non
      obese men. METHODS: Sixteen men were allocated in two different groups, training
      group (N.=10) performed a combined HIIT (5 km, 1 minute of effort interspersed by
      1 minute of rest in passive recovery) followed by strength exercise session
      (three sets, with load of 8-12 repetition maximum) twice a week, during 8 weeks,
      while control group (N.=6) did not suffer any intervention. Hunger scores, leptin
      concentrations and body composition were assessed. Body composition, fasting
      leptin and hunger score were compared through two-way analysis (group and period)
      with repeated measures in the second factor while leptin and hunger scores in
      exercise session pre- and post-8 weeks through two-way analysis (period and time
      of measurement) with repeated measures in the second factor. RESULTS: The fasting
      leptin decreased pre- to post-8week in training group (7.7+/-4.9 to 2.9+/-2.1
      ng/mL; P=0.012). For leptin response to exercise session there was main effect of
      training period, with higher values pre- (6.5+/-3.9 ng/mL) than post-training
      (2.6+/-2.1 ng/mL; P<0.001). For hunger scores there was effect of time of
      measurement (P<0.001), decreasing after breakfast and increasing over the
      experiment. CONCLUSIONS: Combined HIIT plus strength training were able to
      promote alterations in a hormone related to energy balance independent of body
      composition and hunger index alterations in physically active non-obese men.

PMID- 28488832
TI  - Road to the Olympics: physical fitness of medalists of the Canoe Sprint Junior
      European and World Championship events over the past 20 years.
AB  - BACKGROUND: In this article we aimed to find out whether there is a difference in
      physiological, anthropometric and power variables between medalists in junior
      international Championship events (MJCH) and the remaining members of the
      national team (NT) in flat water canoe sprint. METHODS: Sixty male junior
      kayakers from Slovak NT were tested annually between years 1995 and 2016. Sixteen
      of them won at least one medal (gold, silver or bronze) at junior international
      Championship. Exercise capacity assessment on treadmill running (TR) and kayak
      ergometer (KE), anthropometric and muscle power measurements were performed
      between years 1995 and 2016. RESULTS: MJCH were on average by 10% better in TR
      speed and KE power output at VO2max than the rest of NT (19.72+/-0.8 vs. 18+/-1.0
      km.h-1, P<0.01, ES=1.84; 206.6+/-21.5 vs. 182.3+/-25.5 W, P<0.01, ES=0.99,
      respectively). Similarly mean maximal power in bench press and bench pull was
      higher in MJCH (522.9+/-72.0 vs. 464.3+/-69.0 W, P<0.01; ES=0.84; 629.15+/-63.3
      vs. 571.6+/-58.7 W, P<0.01; ES=0.96, respectively). CONCLUSIONS: These data show
      that an athlete has to be on average by 10% better in physical fitness than the
      rest of NT to take podium position at canoe sprint junior international
      Championship. Prosperous juniors are further successful at senior Championship
      events and Olympics. We assume that high level of physical fitness in junior age
      is not a guarantee but a prerequisite for a successful future career.

PMID- 28488833
TI  - The feasibility of an exercise program 12 months post-stroke in a small urban
      community.
AB  - BACKGROUND: There are few community-based exercise programs catering to
      individuals post-stroke, despite an increasing need. The primary objective of
      this study was to assess the feasibility of running a community-based exercise
      program for individuals post-stroke, and to provide a framework for local
      communities to run similar programs. METHODS: Individuals who had a stroke within
      12 months of the start of the program were eligible to participate in a 9-week
      community-based exercise program. Sit to stand, grip strength, arm curl, timed up
      and-go, 6-minute walk, Berg Balance Scale, Stroke-Specific Quality of Life
      Questionnaire, and Exercise Self-Efficacy Scale were assessed pre- and post
      program to determine the effectiveness of the program. Caregivers of participants
      were invited to participate in a focus group after the program (N.=5) to better
      understand program feasibility and areas for improvement. RESULTS: Individuals (9
      males, 1 female) with stroke were recruited from a local rehabilitation program
      within 1 week (aged 72.7+/-9.3 years). The ratio of volunteers to participants
      was 1:2. All participants completed the exercise program and pre-post-testing.
      Significant improvements were observed for sit to stand (7.6+/-3.4 to 9.8+/-4.3
      repetitions, P<0.01), grip strength of the non-affected side (29.7+/-8.9 to
      32.6+/-8.3 lbs, P=0.04), arm curl (15.2+/-6.1 to 19.9+/-4.7 repetitions, P=0.04),
      and Exercise Self-Efficacy score (Z=2.50, P=0.01, r=0.79) from pre to post
      program. Caregivers suggested increasing the frequency of the program.
      CONCLUSIONS: An effective community-based exercise program for individuals post
      stroke can be run at community centers utilizing qualified volunteers.

PMID- 28488834
TI  - The efficacy of wearable activity tracking technology as part of a weight loss
      program: a systematic review.
AB  - INTRODUCTION: The world obesity rate has increased over the past two decades.
      This problem has been linked to inactivity and lack of exercise among individuals
      which prompted the development of wearable activity tracking technology. This
      technology is commonly offered as a bracelet, watch, or pendent that provides
      feedback of daily activity such as total step count, heart rate, and energy
      expenditure. Despite the popularity of these devices, their efficacy to assist in
      behavior change and weight loss is still being studied. The purpose of this
      systematic review was to appraise the current evidence on the efficacy of
      wearable activity devices when used in a comprehensive weigh loss program.
      EVIDENCE ACQUISITION: A systematic review was conducted according the PRISMA
      guidelines. A search of electronic databases was conducted through December 2016
      using the following keywords: activity monitor, consumer, wearable, technology,
      Fitbit(r), Garmin(r), Jawbone(r), physical, activity, tracker, weight loss,
      walking, pedometer, accelerometer, step count, calories, obesity, digital, self
      monitoring, and mobile health (mHealth). The grading of studies was conducted
      using the PEDro scale. EVIDENCE SYNTHESIS: We identified 7184 citations, 25 met
      the inclusion criteria. Twenty-one studies scored a 6 or higher and four studies
      scored a 5 on the PEDro scale. All subjects had a Body Mass Index (BMI) of >=25
      kg/m2 and were mostly women. CONCLUSIONS: The results suggests that short-term
      (<6 months) weight loss interventions using activity trackers may be a better
      option than a standard weight loss program in middle age or older adults. Younger
      adults may not benefit from such technology.

PMID- 28488835
TI  - Incidence of injury and illness in South African professional male soccer
      players: a prospective cohort study.
AB  - BACKGROUND: Medical illnesses and sports-related injuries both have an effect on
      athlete health and performance. Epidemiology of injury and illness has been
      extensively researched during international soccer tournaments and the European
      soccer season. Reports on injury location and severity differ across geographical
      regions, and there is limited information on injury epidemiology in African
      soccer leagues. No studies have investigated the illness burden in soccer in
      Africa. METHODS: This was a prospective cohort study involving two soccer teams
      over the 10-month duration of the 2015/16 Premier Soccer League in South Africa.
      Team medical staff recorded daily soccer exposure, illness and injuries. Team
      based match and training exposure was calculated and used to determine injury and
      illness incidence and burden over the soccer season. RESULTS: Overall injury
      incidence was 2.2/1000 hours, with match injury incidence of 24.8/1000 hours and
      training injury incidence of 0.9/1000 hours. Time loss injuries accounted for 33
      of the 44 injuries recorded. The most common time loss injury location was the
      knee (14 injuries, 42%). There were 7 minimal, 4 mild, 12 moderate and 10 severe
      injuries. Sprain/ligament injury (8 injuries) was the most common type, followed
      by meniscus/cartilage injury (7 injuries). Eleven illnesses were reported during
      the season, with an incidence of 0.7/1000 player days, and most were minimal in
      severity (8/11). The illness burden was 1.7/1000 player days. The respiratory
      (46%) and gastrointestinal (36%) systems were most commonly affected.
      CONCLUSIONS: The incidence of injury was comparable with data reported
      internationally and mirrors the increased risk of injury during matches versus
      training. The nature of injury differed in that the knee was more frequently
      affected than the ankle or thigh, joint injuries were more common than muscle
      injuries, and there was a larger proportion of severe injuries. The illness
      burden was very low.

PMID- 28488836
TI  - Effects of low-load resistance exercise with blood flow restriction on
      intramuscular hemodynamics, oxygenation level and water content.
AB  - BACKGROUND: Muscle metabolism during and after low-load blood flow restriction
      (BFR) exercise should be further investigated to clarify the mechanism by which
      the exercise leads to muscle hypertrophy, and increases strength and endurance.
      We aimed to investigate the effects of low-load resistance exercise with BFR on
      intramuscular hemodynamics, oxygenation level, and water content. METHODS: Seven
      men performed ankle plantar flexion exercise (120 repetitions, 30% one repetition
      maximum) using a custom-made device with and without BFR inside a magnetic
      resonance scanner. Changes in the total hemoglobin/myoglobin concentration and
      Tissue Oxygenation Index (TOI) within the medial gastrocnemius were evaluated
      before, during, and after exercise using near-infrared spectroscopy.
      Intramuscular water content was evaluated before and after exercise by
      calculating an apparent diffusion coefficient (ADC) using magnetic resonance
      diffusion-weighted imaging. RESULTS: The TOI significantly decreased during BFR
      and non-restricted exercises, and significantly increased after BFR exercise;
      compared to the non-restricted condition, the BFR condition showed significantly
      greater changes in the TOI during and after exercise. The total
      hemoglobin/myoglobin concentration significantly increased during and after
      exercise in both exercise conditions; the BFR condition temporarily showed
      significantly greater values during and after exercise. Although the ADC values
      significantly elevated after BFR and non-restricted exercises, the elevation was
      significantly greater in the BFR condition. CONCLUSIONS: Compared to non
      restricted exercise, low-load BFR exercise exposes an exercising muscle to
      greater hypoxic and hyperemic environments. Moreover, BFR exercise not only
      elevates muscle oxygenation level, but also results in greater muscle swelling
      and reactive hyperemia than those observed after non-restricted exercise.

PMID- 28488837
TI  - Allometric associations between body size, shape, and 100-m butterfly speed
      performance.
AB  - BACKGROUND: This study aimed to estimate the optimal body size, limb-segment
      length, and girth or breadth ratios associated with 100-m butterfly speed
      performance in swimmers. METHODS: One-hundred-sixty-seven swimmers as subjects
      (male: N.=103; female: N.=64). Anthropometric measurements comprised height, body
      mass, skinfolds, arm-span, upper-limb-length, upper-arm, forearm, hand-lengths,
      lower-limb-length, thigh-length, leg-length, foot-length, arm-relaxed-girth,
      forearm-girth, wrist-girth, thigh-girth, calf-girth, ankle-girth, biacromial and
      biiliocristal-breadths. To estimate the optimal body size and body composition
      components associated with 100-m butterfly speed performance, we adopted a
      multiplicative allometric log-linear regression model, which was refined using
      backward elimination. RESULTS: Fat-mass was the singularly most important whole
      body characteristic. Height and body-mass did not contribute to the model. The
      allometric model identified that having greater limb segment length-ratio (arm
      ratio = [arm-span]/[forearm]) and limb girth-ratio (girth-ratio = [calf
      girth]/[ankle-girth]) were key to butterfly speed performance. A greater arm-span
      to forearm-length ratio and a greater calf to ankle-girth-ratio suggest that a
      combination of larger arm-span and shorter forearm-length and the combination of
      larger calves and smaller ankles-girth may benefit butterfly swim speed
      performance. In addition having greater biacromial and biliocristal breadths is
      also a major advantage in butterfly swimming speed performance. Finally, the
      estimation of these ratios was made possible by adopting a multiplicative
      allometric model that was able to confirm, theoretically, that swim speeds are
      nearly independent of total body size. CONCLUSIONS: The 100-m butterfly speed
      performance was strongly negatively associated with fat mass and positively
      associated with the segment length ratio (arm-span/forearm-length) and girth
      ratio (calf-girth)/(ankle-girth), having controlled for the developmental changes
      in age.

PMID- 28488838
TI  - Caring for Patients with Service Dogs: Information for Healthcare Providers
AB  - People with disabilities use various assistance devices to improve their capacity
      to lead independent and fulfilling lives. Service dogs can be crucial lifesaving
      companions for their owners. As the use of service dogs increases, nurses are
      more likely to encounter them in healthcare settings. Service dogs are often
      confused with therapy or emotional support dogs. While some of their roles
      overlap, service dogs have distinct protection under the American Disabilities
      Act (ADA). Knowing the laws and proper procedures regarding service dogs
      strengthens the abilities of healthcare providers to deliver holistic, patient
      centered care. This article provides background information about use of dogs,
      and discusses benefits to patients and access challenges for providers. The
      author reviews ADA laws applicable to service dog use and potential challenges
      and risks in acute care settings. The role of the healthcare professional is
      illustrated with an exemplar, along with recommendations for future research and
      nursing implications related to care of patients with service dogs.

PMID- 28488839
TI  - Nurses Need Not Be Guilty Bystanders: Caring for Vulnerable Immigrant Populations
AB  - Nurses face many dilemmas when providing healthcare to immigrants, a vulnerable
      population. Racist, rancorous dialogue can create a hostile care environment that
      may place patients at risk for substandard care. This article presents a two part
      case study about a Hispanic patient to illustrate both examples of inappropriate
      dialogue (Part I) and potential nursing actions (Part 2). The authors review
      myths versus facts about Hispanic immigrants and introduce activist Thomas
      Merton's concept of the guilty bystander, the nursing professional code of
      ethics, and Professor Joseph Badaracco's concepts of quiet leadership as
      practical tools and approaches that nurses can use to advocate for safe, quality,
      ethical care of immigrant populations.

PMID- 28488840
TI  - Bladder cancer and Th1 chemokines
AB  - Bladder cancer arises from the epithelial lining of the urinary bladder, and it
      is known as transitional cell carcinoma (TCC). Tobacco smoking is the main known
      contributor to urinary bladder cancer. However thirty percent of bladder tumors
      probably result from occupational exposure in the workplace to carcinogens.
      Immunotherapy by intravesicular delivery of Bacillus Calmette-Guerin (BCG) is
      used to treat and prevent the recurrence of superficial bladder cancer.
      Successful BCG immunotherapy for bladder cancer is associated with proper
      induction of T helper (Th)1 immunity. In bladder cancer patients after
      intravesicular BCG, urine was found to contain high levels of IP-10, and
      Interferon (IFN)-gamma. TCC and endothelial cell lines were able to secrete IP-10
      in response to BCG or IFN stimulation in vitro. Furthermore intravesicular BCG
      induces a cytokine-rich urinary microenvironment that is inhibitory to human
      endothelial cells and it is anti-angiogenetic by the induction of Th1 chemokines.
      Other studies suggest that therapeutic strategies involving Th1 induction and Th2
      dampening may improve responses to immunotherapy. Further studies are needed to
      evaluate the IP-10 in circulation, and urine, as prognostic marker of bladder
      cancer patients, also in relation to BCG immunotherapy

PMID- 28488841
TI  - Catastrophic antiphospholipid syndrome: an update.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is a rare variant that accounts for
      1% of patients with APS. Despite its low frequency, the mortality-related is very
      high ranging from 50% of patients in the first series to 37% in the most recent
      data. The current knowledge of this potential devastating entity comes from the
      International Registry of patients with CAPS, named CAPS Registry. Small vessel
      thrombosis, laboratory features of microangiopathic haemolytic anemia, and
      development of multisystem involvement in a very short period of time are the
      main characteristics of this syndrome. Clinical manifestations are due to
      thrombosis but also, although the evidences are indirect, to excess of
      proinflammatory cytokines. Therefore, treatment strategy is based on the
      combination of anticoagulation, glucocorticoids, plasma exchange and/or
      intravenous immunoglobulins, the so-called triple therapy. In refractory cases or
      in those with initial life-threatening situation, rituximab may be an effective
      option. Recently, some cases of CAPS have been effectively treated with the
      addition of eculizumab to the triple therapy.

PMID- 28488842
TI  - Sleep-disordered breathing in heart failure patients after ventricular assist
      device implantation and heart transplantation.
AB  - Chronic heart failure (CHF) represents a major health and economic burden and is
      associated with high rates of hospital admission, morbidity, mortality and
      decreased quality-adjusted life years. New advances in the treatment of CHF such
      as ventricular assist devices (VADs) and heart transplantation have helped
      improve outcomes. Sleep-disordered breathing (SDB) is highly prevalent in CHF
      patients and the associated morbidity makes it essential for physicians to be
      more cognizant about its existence, interaction and need for treatment. This is a
      review of what is known to date about SDB in CHF patients who have undergone
      advanced treatments with VADs and/or heart transplantation.

PMID- 28488843
TI  - HOTAIR and gastric cancer: a lesson from two meta-analyses.

PMID- 28488844
TI  - Magnetic resonance imaging in prostate cancer detection and management: a
      systematic review.
AB  - INTRODUCTION: The aim of our work was to evaluate the role of multi-parametric
      magnetic resonance imaging (mpMRI) in detection and management of prostate cancer
      (PC); specifically investigating the efficacy of mpMRI-based biopsy techniques in
      terms of diagnostic yield of significant prostate neoplasm and the improved
      management of patients who choose conservative treatments or active surveillance.
      EVIDENCE ACQUISITION: A systematic and critical analysis through Medline, Embase,
      Scopus and Web of Science databases was carried out in March 2016, following the
      PRISMA ("Preferred Reporting Items for Systematic Reviews and Meta-Analyses")
      statement. The search was conducted using the following key words: "MRI/TRUS
      fusion biopsy," "PIRADS," "prostate cancer," "magnetic resonance imaging (MRI),"
      "multiparametric MRI (mpMRI)," "systematic prostate biopsy (SB)," "targeted
      prostate biopsy (TPB)." English language articles were reviewed for inclusion
      ability. EVIDENCE SYNTHESIS: Sixty-six studies were selected in order to evaluate
      the characteristics and limitations of traditional sample biopsy, the role of
      mpMRI in detection of PC, specifically the increased degree of diagnostic
      accuracy of targeted prostate biopsy compared to systematic biopsy (12 cores),
      and to transperineal saturation biopsies with trans-rectal ultrasound (TRUS)
      only. MpMRI can detect index lesions in approximately 90% of cases when compared
      to prostatectomy specimen. The diagnostic performance of biparametric MRI (T2w +
      DWI) is not inferior to mpMRI, offering valid options to diminish cost- and time
      consumption. Since approximately 10% of significant lesions are still MRI
      invisible, systematic cores biopsy seem to still be necessary. The analysis of
      the different techniques shows that in-bore MRI-guided biopsy and MRI/TRUS-fusion
      guided biopsy are superior in detection of significant PC compared to visual
      estimation alone. MpMRI proved to be very effective in active surveillance, as it
      prevents underdetection of significant PC and it assesses low-risk disease
      accurately. In higher-risk disease, presurgical MRI may change the clinically
      based surgical plan in up to a third of cases. CONCLUSIONS: Targeted prostate
      biopsy, guided by mpMRI, is able to improve diagnostic accuracy and to reduce the
      detection of insignificant PC. Since the negative predictive value (NPV) of mpMRI
      is still imperfect, systematic cores biopsy should not be omitted for optimal
      staging of disease. A process of a progressive and periodic evolution in the
      detection and radiological classification of prostate lesions (such as PIRADS),
      is still needed in patients in active surveillance and in radical prostatectomy
      planning.

PMID- 28488845
TI  - The Babylonian confusion in describing chronic changes in renal allografts.

PMID- 28488846
TI  - Impact of Film Thickness of Ultrathin Dip-Coated Compact TiO2 Layers on the
      Performance of Mesoscopic Perovskite Solar Cells.
AB  - Uniform and pinhole-free electron-selective TiO2 layers are of utmost importance
      for efficient perovskite solar cells. Here we used a scalable and low-cost dip
      coating method to prepare uniform and ultrathin (5-50 nm) compact TiO2 films on
      fluorine-doped tin oxide (FTO) glass substrates. The thickness of the film was
      tuned by changing the TiCl4 precursor concentration. The formed TiO2 follows the
      texture of the underlying FTO substrates, but at higher TiCl4 concentrations, the
      surface roughness is substantially decreased. This change occurs at a film
      thickness close to 20-30 nm. A similar TiCl4 concentration is needed to produce
      crystalline TiO2 films. Furthermore, below this film thickness, the underlying
      FTO might be exposed resulting in pinholes in the compact TiO2 layer. When
      integrated into mesoscopic perovskite solar cells there appears to be a similar
      critical compact TiO2 layer thickness above which the devices perform more
      optimally. The power conversion efficiency was improved by more than 50% (from
      5.5% to ~8.6%) when inserting a compact TiO2 layer. Devices without or with very
      thin compact TiO2 layers display J-V curves with an "s-shaped" feature in the
      negative voltage range, which could be attributed to immobilized negative ions at
      the electron-extracting interface. A strong correlation between the magnitude of
      the s-shaped feature and the exposed FTO seen in the X-ray photoelectron
      spectroscopy measurements indicates that the s-shape is related to pinholes in
      the compact TiO2 layer when it is too thin.

PMID- 28488847
TI  - A Superior Polymer Electrolyte with Rigid Cyclic Carbonate Backbone for
      Rechargeable Lithium Ion Batteries.
AB  - The fabricating process of well-known Bellcore poly(vinylidene fluoride
      hexafluoropropylene) (PVdF-HFP)-based polymer electrolytes is very complicated,
      tedious, and expensive owing to containing a large amount of fluorine
      substituents. Herein, a novel kind of poly(vinylene carbonate) (PVCA)-based
      polymer electrolyte is developed via a facile in situ polymerization method,
      which possesses the merits of good interfacial compatibility with electrodes. In
      addition, this polymer electrolyte presents a high ionic conductivity of 5.59 *
      10-4 S cm-1 and a wide electrochemical stability window exceeding 4.8 V vs Li+/Li
      at ambient temperature. In addition, the rigid cyclic carbonate backbone of
      poly(vinylene carbonate) endows polymer electrolyte a superior mechanical
      property. The LiFe0.2Mn0.8PO4/graphite lithium ion batteries using this polymer
      electrolyte deliver good rate capability and excellent cyclability at room
      temperature. The superior performance demonstrates that the PVCA-based
      electrolyte via in situ polymerization is a potential alternative polymer
      electrolyte for high-performance rechargeable lithium ion batteries.

PMID- 28488848
TI  - Directionally Interacting Spheres and Rods Form Ordered Phases.
AB  - The structures formed by mixtures of dissimilarly shaped nanoscale objects can
      significantly enhance our ability to produce nanoscale architectures. However,
      understanding their formation is a complex problem due to the interplay of
      geometric effects (entropy) and energetic interactions at the nanoscale. Spheres
      and rods are perhaps the most basic geometrical shapes and serve as convenient
      models of such dissimilar objects. The ordered phases formed by each of these
      individual shapes have already been explored, however, when mixed, spheres and
      rods have demonstrated only limited structural organization to date. Here, we
      show using experiments and theory that the introduction of directional
      attractions between rod ends and isotropically interacting spherical
      nanoparticles (NPs) through DNA base pairing leads to the formation of ordered
      three-dimensional lattices. The spheres and rods arrange themselves in a complex
      alternating manner, where the spheres can form either a face-centered cubic (FCC)
      or hexagonal close-packed (HCP) lattice, or a disordered phase, as observed by in
      situ X-ray scattering. Increasing NP diameter at fixed rod length yields an
      initial transition from a disordered phase to the HCP crystal, energetically
      stabilized by rod-rod attraction across alternating crystal layers, as revealed
      by theory. In the limit of large NPs, the FCC structure is instead stabilized
      over the HCP by rod entropy. We, therefore, propose that directionally specific
      attractions in mixtures of anisotropic and isotropic objects offer insight into
      unexplored self-assembly behavior of noncomplementary shaped particles.

PMID- 28488850
TI  - Fabrication of Polyimide Membrane Incorporated with Functional Graphene Oxide for
      CO2 Separation: The Effects of GO Surface Modification on Membrane Performance.
AB  - Two kinds of isocyanate were used to modify graphene oxide (GO) samples. Then,
      polyimide (PI) hybrid membranes containing GO and modified GO were prepared by in
      situ polymerization. The permeation of CO2 and N2 was studied using these novel
      membranes. The morphology experiments showed that the isocyanate groups were
      successfully grafted on the surface of GO by replacement of the oxygen-containing
      functional groups. After modification, the surface polarity of the GO increased,
      and more defect structures were introduced into the GO surface. This resulted in
      a good distribution of more modified GO samples in the PI polymer matrix. Thus,
      the PI hybrid membranes incorporated by modified GO samples showed a high gas
      permeability and ideal selectivity of membranes. In addition, enhancement of the
      selectivity due to the solubility of CO2 played a major role in the increase in
      the separation performance of the hybrid membranes for CO2, although the
      diffusion coefficients for CO2 also increased. Both the higher condensability and
      the strong affinity between CO2 molecules and GO in the polymer matrix caused an
      enhancement of the solubility selectivity higher than the diffusion selectivity
      after GO surface modification.

PMID- 28488851
TI  - Simultaneous Surface-Enhanced Raman Spectroscopy Detection of Multiplexed
      MicroRNA Biomarkers.
AB  - Simultaneous detection of cancer biomarkers holds great promise for the early
      diagnosis of cancer. In the present work, an ultrasensitive and reliable surface
      enhanced Raman scattering (SERS) sensor has been developed for simultaneous
      detection of multiple liver cancer related microRNA (miRNA) biomarkers. We first
      proposed a novel strategy for the synthesis of nanogap-based SERS nanotags by
      modifying gold nanoparticles (AuNPs) with thiolated DNA and nonfluorescent small
      encoding molecules. We also explored a simple approach to a green synthesis of
      hollow silver microspheres (Ag-HMSs) with bacteria as templates. On the basis of
      the sandwich hybridization assay, probe DNA-conjugated SERS nanotags used as SERS
      nanoprobes and capture DNA-conjugated Ag-HMSs used as capture substrates were
      developed for the detection of target miRNA with a detection limit of 10 fM.
      Multiplexing capability for simultaneous detection of the three liver cancer
      related miRNAs with the high sensitivity and specificity was demonstrated using
      the proposed SERS sensor. Furthermore, the practicability of the SERS sensor was
      supported by the successful determination of target miRNA in cancer cells. The
      experimental results indicated that the proposed strategy holds significant
      potential for multiplex detection of cancer biomarkers and offers the opportunity
      for future applications in clinical diagnosis.

PMID- 28488849
TI  - Solution Conformations and Dynamics of Substrate-Bound Cytochrome P450 MycG.
AB  - MycG is a P450 monooxygenase that catalyzes the sequential hydroxylation and
      epoxidation of mycinamicin IV (M-IV), the last two steps in the biosynthesis of
      mycinamicin II, a macrolide antibiotic isolated from Micromonospora griseorubida.
      The crystal structure of MycG with M-IV bound was previously determined but
      showed the bound substrate in an orientation that did not rationalize the
      observed regiochemistry of M-IV hydroxylation. Nuclear magnetic resonance
      paramagnetic relaxation enhancements provided evidence of an orientation of M-IV
      in the MycG active site more compatible with the observed chemistry, but
      substrate-induced changes in the enzyme structure were not characterized. We now
      describe the use of amide 1H-15N residual dipolar couplings as experimental
      restraints in solvated "soft annealing" molecular dynamics simulations to
      generate solution structural ensembles of M-IV-bound MycG. Chemical shift
      perturbations, hydrogen-deuterium exchange, and 15N relaxation behavior provide
      insight into the dynamic and electronic perturbations in the MycG structure in
      response to M-IV binding. The solution and crystallographic structures are
      compared, and the possibility that the crystallographic orientation of bound M-IV
      represents an inhibitory mode is discussed.

PMID- 28488852
TI  - Structure and Dynamics of the Tetra-A Loop and (A-A)-U Sequence Motif within the
      Coliphage GA Replicase RNA Operator.
AB  - The three-dimensional structure of a RNA hairpin containing the RNA operator
      binding site for bacteriophage GA coat protein is presented. The phage GA
      operator contains the asymmetric (A-A)-U sequence motif and is capped by a four
      adenine (tetra-A) loop. The uridine of the (A-A)-U motif preferentially pairs
      with the 5'-proximal cross-strand adenine, and the 3'-proximal adenine stacks
      into the helix. The tetra-A loop is well-ordered with adenine residues 2-4
      forming a 3' stack. This loop conformation stands in contrast to the structure of
      the 5'-AUUA loop of the related phage MS2 operator in which residues 1 and 2 form
      a 5' stack. The context dependence of the (A-A)-U sequence motif conformation was
      examined using structures of 76 unique occurrences from the Protein Data Bank.
      The motif almost always has one adenine bulged and the other adenine adopting an
      A-U base pair. In the case in which the (A-A)-U motif is flanked by only one
      Watson-Crick base pair, the adenine adjacent to the flanking base pair tends to
      bulge; 80% of motifs with a 3' flanking pair have a 3' bulged adenine, and 84% of
      motifs with a 5' flanking pair have a 5' bulged adenine. The frequencies of 3'-
      and 5'-proximal adenines bulging are 33 and 67%, respectively, when the (A-A)-U
      motif is flanked by base pairs on both sides. Although a 3' flanking cytidine
      correlates (88%) with bulging of the 5'-proximal adenine, no strict dependence on
      flanking nucleotide identity was identified for the 5' side.

PMID- 28488853
TI  - Metal-Organic Framework Template Synthesis of NiCo2S4@C Encapsulated in Hollow
      Nitrogen-Doped Carbon Cubes with Enhanced Electrochemical Performance for Lithium
      Storage.
AB  - Owing to its richer redox reaction and remarkable electrical conductivity,
      bimetallic nickel cobalt sulfide (NiCo2S4) is considered as an advanced electrode
      material for energy-storage applications. Herein, nanosized NiCo2S4@C
      encapsulated in a hollow nitrogen-doped carbon cube (NiCo2S4@D-NC) has been
      fabricated using a core@shell Ni3[Co(CN)6]2@polydopamine (PDA) nanocube as the
      precursor. In this composite, the NiCo2S4 nanoparticles coated with conformal
      carbon layers are homogeneously embedded in a 3D high-conduction carbon shell
      from PDA. Both the inner and the outer carbon coatings are helpful in increasing
      the electrical conductivity of the electrode materials and prohibit the
      polysulfide intermediates from dissolving in the electrolyte. When researched as
      electrode materials for lithium storage, owing to the unique structure with
      double layers of nitrogen-doped carbon coating, the as-obtained NiCo2S4@D-NC
      electrode maintains an excellent specific capacity of 480 mAh g-1 at 100 mA g-1
      after 100 cycles. Even after 500 cycles at 500 mA g-1, a reversible capacity of
      427 mAh g-1 can be achieved, suggesting an excellent rate capability and an
      ultralong cycling life. This remarkable lithium storage property indicates its
      potential application for future lithium-ion batteries.

PMID- 28488854
TI  - Long-Life Lithium-Sulfur Battery Derived from Nori-Based Nitrogen and Oxygen Dual
      Doped 3D Hierarchical Biochar.
AB  - Due to restrictions on the low conductivity of sulfur and soluble polysulfides
      during discharge, lithium sulfur batteries are unsuitable for further large scale
      applications. The current carbon based cathodes suffer from poor cycle stability
      and high cost. Recently, heteroatom doped carbons have been considered as a
      settlement to enhance the performance of lithium sulfur batteries. With this
      strategy, we report the low cost activated nori based N,O-doped 3D hierarchical
      carbon material (ANC) as a sulfur host. The N,O dual-doped ANC reveals an
      elevated electrochemical performance, which exhibits not only a good rate
      performance over 5 C, but also a high sulfur content of 81.2%. Further
      importantly, the ANC represents an excellent cycling stability, the cathode
      reserves a capacity of 618 mAh/g at 2 C after 1000 cycles, which shows a 0.022%
      capacity decay per cycle.

PMID- 28488855
TI  - Filtration and Electrochemical Disinfection Performance of PAN/PANI/AgNWs-CC
      Composite Nanofiber Membrane.
AB  - The removal and inactivation of waterborne pathogens from drinking water are
      important for human health. Here, a polyacrylonitrile/polyaniline/silver
      nanowires-carbon fiber cloth (PAN/PANI/AgNWs-CC) composite nanofiber membrane was
      fabricated using a simple and rapid coelectrospinning process, and an electrical
      device was applied with the PAN/PANI/AgNWs-CC filter for water electrochemical
      disinfection. The effects of voltage, flow rate, and microbial concentration on
      the filtration and electrochemical disinfection performance of the nanocomposite
      membrane were investigated. The characterization results show that PAN/PANI/AgNWs
      with uniform diameters and without beads were successfully fabricated on CC.
      AgNWs were uniformly distributed in the PAN/PANI/AgNWs. The PAN/PANI/AgNWs-CC
      filter was an effective sieve for completely removing both Escherichia coli and
      Staphylococcus aureus in the absence of applied voltage, and the sieved bacteria
      were completely inactivated by the released silver within 8 h. Over 99.999%
      inactivation of the sieved bacteria was achieved within a few seconds by
      concurrent filtration and electrochemical disinfection under a voltage of 3 V.
      This high performance is enabled by means of an electrical mechanism, and an
      extremely high electric field induces sharp AgNWs tips to generate electroporated
      pores in the bacteria. The electrochemical PAN/PANI/AgNWs-CC membrane is an
      excellent material with potential application value in point-of-use drinking
      water treatment.

PMID- 28488856
TI  - Light-Driven Hydrogen Generation from Microemulsions Using Metallosurfactant
      Catalysts and Oxalic Acid.
AB  - A unique microemulsion-based photocatalytic water reduction system is
      demonstrated. Iridium- and rhodium-based metallosurfactants, namely,
      [Ir(ppy)2(dhpdbpy)]Cl and [Rh(dhpdbpy)2Cl2]Cl (where ppy = 2-phenylpyridine and
      dhpdbpy = 4,4'-diheptadecyl-2,2'-bipyridine), were employed as photosensitizer
      and proton reducing catalyst, respectively, along with oxalic acid as a
      sacrificial reductant in a toluene/water biphasic mixture. The addition of 1
      octylamine is proposed to initiate the reaction, by coupling with oxalic acid to
      form an ion pair, which acts as an additional surfactant. Concentration
      optimizations yielded high activity for both the photosensitizer (240 turnovers,
      turnover frequency (TOF) = 200 h-1) and catalyst (400 turnovers, TOF = 230 h-1),
      with the system generating hydrogen even after 95 h. Mechanistic insights were
      provided by gas-phase Raman, electrochemical, and luminescence quenching
      analysis, suggesting oxidative quenching to be the principle reaction pathway.

PMID- 28488857
TI  - A Regioselective Synthesis of 6-Alkyl- and 6-Aryluracils by Cs2CO3- or K3PO4
      Promoted Dimerization of 3-Alkyl- and 3-Aryl-2-Propynamides.
AB  - A regioselective synthesis of 6-alkyl- and 6-aryluracils was developed by the
      dimerization of 3-alkyl- and 3-aryl-2-propynamides promoted by either Cs2CO3 or
      K3PO4. A range of 3-aryl-2-propynamides, with both electron-deficient and
      electron-rich 3-aryl substituents, were successfully reacted in high yields. Cs+
      acts as a soft Lewis acid to polarize the carbon-carbon triple bond, and solid
      K3PO4 interacts with carbonyl oxygen, promoting intermolecular nucleophilic
      attack by the only weakly nucleophilic amide nitrogen. Experiments were conducted
      to support the proposed mechanism.

PMID- 28488858
TI  - Development of a High-Throughput Ion-Exchange Resin Characterization Workflow.
AB  - A novel high-throughout (HTR) ion-exchange (IEX) resin workflow has been
      developed for characterizing ion exchange equilibrium of commercial and
      experimental IEX resins against a range of different applications where water
      environment differs from site to site. Because of its much higher throughput,
      design of experiment (DOE) methodology can be easily applied for studying the
      effects of multiple factors on resin performance. Two case studies will be
      presented to illustrate the efficacy of the combined HTR workflow and DOE method.
      In case study one, a series of anion exchange resins have been screened for
      selective removal of NO3- and NO2- in water environments consisting of multiple
      other anions, varied pH, and ionic strength. The response surface model (RSM) is
      developed to statistically correlate the resin performance with the water
      composition and predict the best resin candidate. In case study two, the same HTR
      workflow and DOE method have been applied for screening different cation exchange
      resins in terms of the selective removal of Mg2+, Ca2+, and Ba2+ from high total
      dissolved salt (TDS) water. A master DOE model including all of the cation
      exchange resins is created to predict divalent cation removal by different IEX
      resins under specific conditions, from which the best resin candidates can be
      identified. The successful adoption of HTR workflow and DOE method for studying
      the ion exchange of IEX resins can significantly reduce the resources and time to
      address industry and application needs.

PMID- 28488859
TI  - Enhanced Cytotoxicity and Reactivity of a Novel Platinum(IV) Family with DNA
      Targeting Naphthalimide Ligands.
AB  - Pt(IV) complexes are known as prodrugs that can potentially overcome cisplatin
      limitations by slowing down its reactivity and, once reduced, act as the
      corresponding Pt(II) drugs. We report a new approach toward trans Pt(IV)
      complexes, conceived to afford nonconventional active trans Pt(II) complexes with
      dual-targeting properties. The reduction of the complexes has been studied in the
      presence of ascorbic acid and glutathione, showing that different species are
      formed in the process. The interaction with DNA after reduction has been also
      studied and correlated to the formation of Pt(II) species. The cytotoxicity
      profile of the Pt(IV) complexes corroborated the rationale behind this approach.

PMID- 28488860
TI  - Flexible and Highly Photosensitive Electrolyte-Gated Organic Transistors with
      Ionogel/Silver Nanowire Membranes.
AB  - Flexible and low-voltage photosensors with high near-infrared (NIR) sensitivity
      are critical for realization of interacting humans with robots and environments
      by thermal imaging or night vision techniques. In this work, we for the first
      time develop an easy and cost-effective process to fabricate flexible and
      ultrathin electrolyte-gated organic phototransistors (EGOPTs) with high
      transparent nanocomposite membranes of high-conductivity silver nanowire (AgNW)
      networks and large-capacitance iontronic films. A high responsivity of 1.5 * 103
      A.W1-, high sensitivity of 7.5 * 105, and 3 dB bandwidth of ~100 Hz can be
      achieved at very low operational voltages. Experimental studies in temporal
      photoresponse characteristics reveal the device has a shorter photoresponse time
      at lower light intensity since strong interactions between photoexcited hole
      carriers and anions induce extra long-lived trap states. The devices, benefiting
      from fast and air-stable operations, provide the possibility of the organic
      photosensors for constructing cost-effective and smart optoelectronic systems in
      the future.

PMID- 28488861
TI  - Engineering Pt/Pd Interfacial Electronic Structures for Highly Efficient Hydrogen
      Evolution and Alcohol Oxidation.
AB  - Tailoring the interfacial structure of Pt-based catalysts has emerged as an
      effective strategy to improve catalytic activity. However, little attention has
      been focused on investigating the relationship between the interfacial facets and
      their catalytic activity. Here, we design and implement Pd-Pt interfaces with
      controlled heterostructure features by epitaxially growing Pt nanoparticles on Pd
      nanosheets. On the basis of both density functional theory calculation and
      experimental results, we demonstrate that charge transfer from Pd to Pt is highly
      dependent on the interfacial facets of Pd substrates. Therefore, the Pd-Pt
      heterostructure with Pd(100)-Pt interface exhibits excellent activity and long
      term stability for hydrogen evolution and methanol/ethanol oxidation reactions in
      alkaline medium, much better than that with Pd (111)-Pt interface or commercial
      Pt/C. Interfacial crystal facet-dependent electronic structural modulation sheds
      a light on the design and investigation of new heterostructures for high-activity
      catalysts.

PMID- 28488862
TI  - Gardenifolins A-H, Scalemic Neolignans from Gardenia ternifolia: Chiral
      Resolution, Configurational Assignment, and Cytotoxic Activities against the HeLa
      Cancer Cell Line.
AB  - From the tropical plant Gardenia ternifolia Schumach. and Thonn. (Rubiaceae),
      eight stereoisomeric 2,3-dihydrobenzo[b]furan neolignans, named gardenifolins A-H
      (1a-d and 2a-d), were isolated and fully structurally characterized. Reversed
      phase chromatography of a stem bark extract afforded two peaks, viz. mixtures I
      and II, each one consisting of two diastereomers and their respective
      enantiomers. They were resolved and stereochemically analyzed by HPLC on a chiral
      phase coupled to electronic circular dichroism (ECD) spectroscopy, giving single
      ECD spectra of all eight stereoisomers. The double-bond geometries (E or Z) of
      the gardenifolins A-H and their relative configurations (cis or trans) at the
      stereogenic centers C-7 and C-8 in the dihydrofuran ring system were assigned by
      1D and 2D NMR methods, in particular, using NOE difference experiments, whereas
      the absolute configurations of the isolated enantiomers were established by ECD
      spectroscopy by applying the reversed helicity rule. The individual pure
      gardenifolin isomers A-H showed the most different cytotoxic effects against the
      human cancer HeLa cell line, with 1d and 2a displaying the highest activities,
      with IC50 values of 21.0 and 32.5 MUM, respectively. Morphological experiments
      indicated that gardenifolin D (1d) induces apoptosis of HeLa cells at 25 MUM.

PMID- 28488863
TI  - V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein.
AB  - Inteins mediate protein splicing, which has found extensive applications in
      protein science and biotechnology. In the Mycobacterium tuberculosis RecA mini
      mini intein (DeltaDeltaIhh), a single valine to leucine substitution at position
      67 (V67L) dramatically increases intein stability and activity. However, crystal
      structures show that the V67L mutation causes minimal structural rearrangements,
      with a root-mean-square deviation of 0.2 A between DeltaDeltaIhh-V67 and
      DeltaDeltaIhh-L67. Thus, the structural mechanisms for V67L stabilization and
      activation remain poorly understood. In this study, we used intrinsic tryptophan
      fluorescence, high-pressure nuclear magnetic resonance (NMR), and molecular
      dynamics (MD) simulations to probe the structural basis of V67L stabilization of
      the intein fold. Guanidine hydrochloride denaturation monitored by fluorescence
      yielded free energy changes (DeltaGf degrees ) of -4.4 and -6.9 kcal mol-1 for
      DeltaDeltaIhh-V67 and DeltaDeltaIhh-L67, respectively. High-pressure NMR showed
      that DeltaDeltaIhh-L67 is more resistant to pressure-induced unfolding than
      DeltaDeltaIhh-V67 is. The change in the volume of folding (DeltaVf) was
      significantly larger for V67 (71 +/- 2 mL mol-1) than for L67 (58 +/- 3 mL mol-1)
      inteins. The measured difference in DeltaVf (13 +/- 3 mL mol-1) roughly
      corresponds to the volume of the additional methylene group for Leu, supporting
      the notion that the V67L mutation fills a nearby cavity to enhance intein
      stability. In addition, we performed MD simulations to show that V67L decreases
      side chain dynamics and conformational entropy at the active site. It is
      plausible that changes in cavities in V67L can also mediate allosteric effects to
      change active site dynamics and enhance intein activity.

PMID- 28488864
TI  - Temperature and Pressure Dependences of the Reactions of Fe+ with Methyl Halides
      CH3X (X = Cl, Br, I): Experiments and Kinetic Modeling Results.
AB  - The pressure and temperature dependences of the reactions of Fe+ with methyl
      halides CH3X (X = Cl, Br, I) in He were measured in a selected ion flow tube over
      the ranges 0.4 to 1.2 Torr and 300-600 K. FeX+ was observed for all three halides
      and FeCH3+ was observed for the CH3I reaction. FeCH3X+ adducts (for all X) were
      detected in all reactions. The results were interpreted assuming two-state
      reactivity with spin-inversions between sextet and quartet potentials. Kinetic
      modeling allowed for a quantitative representation of the experiments and for
      extrapolation to conditions outside the experimentally accessible range. The
      modeling required quantum-chemical calculations of molecular parameters and
      detailed accounting of angular momentum effects. The results show that the FeX+
      products come via an insertion mechanism, while the FeCH3+ can be produced from
      either insertion or SN2 mechanisms, but the latter we conclude is unlikely at
      thermal energies. A statistical modeling cannot reproduce the competition between
      the bimolecular pathways in the CH3I reaction, indicating that some more direct
      process must be important.

PMID- 28488865
TI  - Correlations in the Solute-Solvent Dynamics Reach Beyond the First Hydration
      Shell of Ions.
AB  - While the real-space structure of solvation shells has been explored for decades,
      a dynamical perspective that directly relies on changes in the H-bond network
      became accessible more recently mainly via far-infrared (THz) spectroscopies. A
      remaining key question is how many hydration shells are affected by ion-induced
      network perturbations. We disclose that theoretical THz difference spectra of
      aqueous salt solutions can be deciphered in terms of only a handful of dipolar
      auto- and cross-correlations, including the second solvation shell. This
      emphasizes the importance of cross-correlations being often neglected in
      multicomponent models. Analogously, experimental THz responses of simple ions can
      be deciphered in a similar way. Dramatic intensity cancellations due to large
      positive and negative contributions are found to effectively shift intensity
      maxima. Thus, THz spectroscopy provides an unprecedented view on the details of
      hydration dynamics, which can be understood by a combination of experiment and
      theory.

PMID- 28488866
TI  - Mechanism, Regio-, and Diastereoselectivity of Rh(III)-Catalyzed Cyclization
      Reactions of N-Arylnitrones with Alkynes: A Density Functional Theory Study.
AB  - Nitrones have been used for rhodium-catalyzed cyclization C-H bond activation and
      O atom transfer of arylnitrones with alkynes by Chang et al. ( J. Am. Chem. Soc.
      2015 , 137 , 4908 - 4911 ). Density functional theory method has been used to
      study the mechanism, regio-, and diastereoselectivity of type reactions. The
      results elucidated that the reaction pathway for Rh(III)-catalyzed cyclization of
      N-arylnitrones with alkyne contains a C-H bond activation, an alkyne insertion
      into Rh-C bond, a reductive elimination to form a Rh(I) complex, an oxidative
      addition leading to N-O cleavage, an imine insertion into the Rh-C bond, and the
      final protonolysis to regenerate the products and the active catalyst. The
      regioselectivity of this reaction with asymmetric alkyne is controlled by the
      electronic effect in alkyne insertion type instead of steric effects. The
      distortion-interaction analysis is also used to explain the regioselectivity. The
      diastereoselectivity is controlled by the imine insertion step. In this step, the
      sterically less hindered transition state is favored, leading to stereoselective
      product formation.

PMID- 28488867
TI  - Experimental and Theoretical Investigation of the Structural Role of Titanium
      Oxide in CaO-P2O5-TiO2 Invert Glass.
AB  - Understanding the structural role of TiO2 in calcium phosphate invert glasses is
      key for developing a new glass design for biomedical applications. Experimental
      and computational analysis methods were used to investigate the impact of TiO2
      substitution in these glasses. Spectroscopic analyses indicated that titanium
      oxide exists as both TiO4 and TiO6 units, leading to the formation of Ti-O-P
      bonds, in spite of depolymerization of the phosphate chains. Classical molecular
      dynamics showed that the presence of TiO2 influences the phosphate units and CaO
      polyhedral structures. The formation of the Ti-O-P bonds caused an increase in
      the network connectivity of the invert glasses, leading to the improvement of the
      glass forming ability and wettability. The addition of TiO2 to calcium phosphate
      invert glasses led to the introduction of bioactivity.

PMID- 28488868
TI  - Long-Range Lattice Engineering of MoTe2 by a 2D Electride.
AB  - Doping two-dimensional (2D) semiconductors beyond their degenerate levels
      provides the opportunity to investigate extreme carrier density-driven
      superconductivity and phase transition in 2D systems. Chemical functionalization
      and the ionic gating have achieved the high doping density, but their effective
      ranges have been limited to ~1 nm, which restricts the use of highly doped 2D
      semiconductors. Here, we report on electron diffusion from the 2D electride
      [Ca2N]+.e- to MoTe2 over a distance of 100 nm from the contact interface,
      generating an electron doping density higher than 1.6 * 1014 cm-2 and a lattice
      symmetry change of MoTe2 as a consequence of the extreme doping. The long-range
      lattice symmetry change, suggesting a length scale surpassing the depletion width
      of conventional metal-semiconductor junctions, was a consequence of the low work
      function (2.6 eV) with highly mobile anionic electron layers of [Ca2N]+.e-. The
      combination of 2D electrides and layered materials yields a novel material design
      in terms of doping and lattice engineering.

PMID- 28488869
TI  - Insights into the Correlation of Aluminum Distribution and Bronsted Acidity in H
      Beta Zeolites from Solid-State NMR Spectroscopy and DFT Calculations.
AB  - Here we utilized 27Al MAS/MQMAS and 31P MAS NMR of quantitative adsorption of
      trimethylphosphine oxide (TMPO) and DFT calculations to elucidate the
      relationship between Al distribution and Bronsted acidity of series H-Beta
      zeolites derived from dealumination of Al-rich H-Beta zeolite. Three types of
      Bronsted acid strengths corresponding to different specific Al T-sites were
      demonstrated. The removal of one framework Al in 5MR2--2Al and 6MR-2Al sites led
      to increasing the Bronsted acid strength of dealuminated H-Beta. Our findings on
      such exact correlation between specific Al distributions and corresponding
      Bronsted acid sites may guide the controlling Al distribution to get desired acid
      properties through zeolite synthesis or finely tuned dealumination, which has a
      great impact on the catalytic activity and selectivity of zeolite catalysts.

PMID- 28488870
TI  - Strong van der Waals Adhesion of a Polymer Film on Rough Substrates.
AB  - We propose that chemically inert polymeric films can enhance van der Waals (vdW)
      forces in the same way as nanofabrication of biomimetic adhesive materials. For
      the vdW adhesion of an ethylene-chlorotrifluoroethylene (ECTFE) film on rough
      metal and dielectric substrates, we present a model that combines microscopic
      quantum-chemistry simulations of the polymer response functions and the
      equilibrium monomer-substrate distance with a macroscopic quantum-electrodynamics
      calculation of the Casimir force between the polymer film and the substrate. We
      predict adhesive forces up to 2.22 kN/mm2, where the effect is reduced by
      substrate roughness and for dielectric surfaces.

PMID- 28488871
TI  - Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH
      Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy.
AB  - Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating
      agents, represents an appealing approach for improving cancer therapy. To
      optimize its therapeutic efficacy, differentially delivering multiple therapeutic
      drugs to target cells is desirable. Here we developed an immunostimulatory
      nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor
      associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ
      945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions
      of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug
      conjugated small particles and BLZ-945, a small molecule inhibitor of colony
      stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be
      preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while
      the small particles carrying Pt-prodrug enable deep tumor penetration as well as
      intracellularly specific drug release to kill more cancer cells. Our studies
      demonstrate that BLZ-945SCNs/Pt outperform their monotherapy counterparts in
      multiple tumor models. The underlying mechanism studies suggest that the designer
      pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but
      also modulates the tumor immune environment to eventually augment the antitumor
      effect of CD8+ cytotoxic T cells through TAMs depletion.

PMID- 28488872
TI  - Luminescent Organic Semiconducting Langmuir Monolayers.
AB  - In recent years, monolayer organic field-effect devices such as transistors and
      sensors have demonstrated their high potential. In contrast, monolayer
      electroluminescent organic field-effect devices are still in their infancy. One
      of the key challenges here is to create an organic material that self-organizes
      in a monolayer and combines efficient charge transport with luminescence. Herein,
      we report a novel organosilicon derivative of oligothiophene-phenylene dimer D2
      Und-PTTP-TMS (D2, tetramethyldisiloxane; Und, undecylenic spacer; P, 1,4
      phenylene; T, 2,5-thiophene; TMS, trimethylsilyl) that meets these requirements.
      The self-assembled Langmuir monolayers of the dimer were investigated by steady
      state and time-resolved photoluminescence spectroscopy, atomic force microscopy,
      X-ray reflectometry, and grazing-incidence X-ray diffraction, and their
      semiconducting properties were evaluated in organic field-effect transistors. We
      found that the best uniform, fully covered, highly ordered monolayers were
      semiconducting. Thus, the ordered two-dimensional (2D) packing of conjugated
      organic molecules in the semiconducting Langmuir monolayer is compatible with its
      high-yield luminescence, so that 2D molecular aggregation per se does not
      preclude highly luminescent properties. Our findings pave the way to the rational
      design of functional materials for monolayer organic light-emitting transistors
      and other optoelectronic devices.

PMID- 28488875
TI  - Absolute and relative morbidity burdens attributable to various illnesses and
      injuries, active component, U.S. Armed Forces, 2016.

PMID- 28488873
TI  - Removal of Differential Capacitive Interferences in Fast-Scan Cyclic Voltammetry.
AB  - Due to its high spatiotemporal resolution, fast-scan cyclic voltammetry (FSCV) at
      carbon-fiber microelectrodes enables the localized in vivo monitoring of
      subsecond fluctuations in electroactive neurotransmitter concentrations. In
      practice, resolution of the analytical signal relies on digital background
      subtraction for removal of the large current due to charging of the electrical
      double layer as well as surface faradaic reactions. However, fluctuations in this
      background current often occur with changes in the electrode state or ionic
      environment, leading to nonspecific contributions to the FSCV data that confound
      data analysis. Here, we both explore the origin of such shifts seen with local
      changes in cations and develop a model to account for their shape. Further, we
      describe a convolution-based method for removal of the differential capacitive
      contributions to the FSCV current. The method relies on the use of a small
      amplitude pulse made prior to the FSCV sweep that probes the impedance of the
      system. To predict the nonfaradaic current response to the voltammetric sweep,
      the step current response is differentiated to provide an estimate of the
      system's impulse response function and is used to convolute the applied waveform.
      The generated prediction is then subtracted from the observed current to the
      voltammetric sweep, removing artifacts associated with electrode impedance
      changes. The technique is demonstrated to remove select contributions from
      capacitive characteristics changes of the electrode both in vitro (i.e., in flow
      injection analysis) and in vivo (i.e., during a spreading depression event in an
      anesthetized rat).

PMID- 28488874
TI  - An Optically Modulated Self-Assembled Resonance Energy Transfer Pass Gate.
AB  - We demonstrate an optically controlled molecular-scale pass gate that uses the
      photoinduced dark states of fluorescent molecules to modulate the flow of
      excitons. The device consists of four fluorophores spatially arranged on a self
      assembled DNA nanostructure. Together, they form a resonance energy transfer
      (RET) network resembling a standard transistor with a source, channel, drain, and
      gate. When the gate fluorophore is directly excited, the device is toggled on.
      Excitons flow freely from the source to the drain, producing strong output
      fluorescence. Without this excitation, exciton flow through the device is
      hindered by absorbing paths along the way, resulting in weak output fluorescence.
      In this Letter, we describe the design and fabrication of the pass gate. We
      perform a steady-state analysis revealing that the on/off fluorescence ratio for
      this particular implementation is ~8.7. To demonstrate dynamic modulation of the
      pass gate, we toggle the gate excitation on and off and measure the corresponding
      change in output fluorescence. We characterize the rise and fall times of these
      transitions, showing that they are faster and/or more easily achieved than other
      methods of RET network modulation. The pass gate is the first dynamic RET-based
      logic gate exclusively modulated by dark states and serves as a proof-of-concept
      device for building more complex RET systems in the future.

PMID- 28488877
TI  - Ambulatory visits, active component, U.S. Armed Forces, 2016.

PMID- 28488876
TI  - Hospitalizations, active component, U.S. Armed Forces, 2016.

PMID- 28488878
TI  - Surveillance snapshot: Illness and injury burdens, reserve component, U.S. Armed
      Forces, 2016.

PMID- 28488879
TI  - Surveillance snapshot: Illness and injury burdens, recruit trainees, active
      component, U.S. Armed Forces, 2016.

PMID- 28488880
TI  - Absolute and relative morbidity burdens attributable to various illnesses and
      injuries, non-service member beneficiaries of the Military Health System, 2016.

PMID- 28488881
TI  - Mindfulness-Based Relapse Prevention for Methadone Maintenance: A Feasibility
      Trial.
AB  - OBJECTIVES: As rates of opiate misuse rise in the United States, so do
      significant associated health and financial consequences to afflicted
      individuals, their families, and society at large. Methadone maintenance therapy
      (MMT) is one evidence-based approach to treating opiate addiction, yet
      supplemental psychosocial treatment to support this approach is lacking.
      Mindfulness-based relapse prevention (MBRP) has shown to be efficacious in
      various substance use populations, but has yet to be assessed with MMT clients.
      DESIGN: The current mixed methods study was designed to inform protocol
      adaptation for MMT clients and to evaluate the feasibility, acceptability, and
      preliminary efficacy of MBRP for this population. SUBJECTS: The sample consisted
      of adults (N = 15) recruited from a methadone clinic to participate in a 6-week
      MBRP course. OUTCOME MEASURES: Data from focus groups and course satisfaction
      surveys supported feasibility and acceptability of the intervention. Self-report
      outcome measures included depression, anxiety, craving, symptoms of post
      traumatic stress, and experiential avoidance, and were assessed at baseline and
      postcourse. RESULTS: Mean scores on all primary outcomes changed in the expected
      direction at postcourse, and baseline to postcourse changes in depression,
      craving, and trauma symptoms reached statistical significance. CONCLUSIONS:
      Results from this initial pilot trial support feasibility and acceptability, and
      provide preliminary data on outcomes for future trials of mindfulness-based
      approaches within the MMT community.

PMID- 28488882
TI  - Development of bioanalytical assays for variegin, a peptide-based bivalent direct
      thrombin inhibitor.
AB  - AIM: Variegin is an anticoagulant peptide that will be tested in porcine models
      of percutaneous coronary intervention. We developed three bioanalytical assays
      for variegin quantitation and utilized these methods to evaluate pharmacokinetics
      of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and
      modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8
      5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half
      lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic
      assays were 52.3 +/- 4.4, 50.4 +/- 5.9 and 67.7 +/- 6.3 min, respectively.
      CONCLUSION: We developed three bioanalytical assays for a novel direct thrombin
      inhibitor, variegin. The thrombin time assay is optimized for variegin
      quantitation during future porcine studies and clinical trials.

PMID- 28488883
TI  - Ultrasensitive bioanalysis: current status and future trends.
AB  - Ligand-binding techniques such as immunoassays, the reference for clinical
      diagnosis, offer a wide range of innovative approaches based on signal DNA
      amplification, nanotechnologies or digital assays, which result in technologies
      with sensitivities more than 1000-times that of formats used 20 years ago.
      Providing that these technologies gain acceptance and translate into robust
      commercial platforms, we expect that several fields will be impacted in the near
      future, including the clinical diagnosis of cancer markers, the early detection
      of infectious diseases and the safety of biotherapeutics. Furthermore, the
      combination of these techniques with microfluidic systems will allow probing of
      biological diversity at the single cell level and will lead to the discovery of
      novel and rare biomarkers.

PMID- 28488884
TI  - Evaluation of a novel risk assessment method for self-harm associated with
      Borderline Personality Disorder.
AB  - OBJECTIVES: Borderline personality disorder (BPD) is associated with frequent
      self-harm and suicidal behaviours. This study compared physician-assessed self
      harm risk and intervention choice according to a (i) standard risk assessment and
      (ii) BPD-specific risk assessment methods. METHODS: Forty-five junior and senior
      mental health physicians were assigned to standard or BPD-specific risk training
      groups. The assessment utilized a BPD case vignette containing four scenarios
      describing high/low lethality self-harm and chronic/new patterns of self-harm
      behaviour. Participants chose from among four interventions, each corresponding
      to a risk category. RESULTS: Standard and BPD-specific groups were alike in their
      assessment of self-harm risk. Divergence occurred on intervention choice for
      assessments of low lethality, chronic risk ( p<.01) and high lethality, chronic
      risk ( p<.005). Overall, psychiatrists were more likely than their junior
      colleagues to correctly assess risk and management options. CONCLUSIONS: Although
      standard and BPD-specific methods are well aligned for assessing self harm
      associated risk, BPD-specific training raised awareness of BPD-appropriate
      interventions, particularly in the context of chronic patterns of self-harm
      behaviour. Wider dissemination of BPD-specific risk training may enhance the
      confidence of mental health clinicians in identifying the nature of self-harm
      risk as well as the most clinically appropriate interventions for clients with
      BPD.

PMID- 28488885
TI  - Respiratory muscle strength and pulmonary function in children with rhinitis and
      asthma after a six-minute walk test.
AB  - OBJECTIVE: Rhinitis and asthma decrease quality of life. Few studies have
      assessed the performance of children with asthma or rhinitis under submaximal
      exercise. We evaluated maximal respiratory pressures, spirometric parameters, and
      ability to sustain submaximal exercise in these children before and after the 6
      minute walk test (6MWT), compared to healthy children. METHODS: This cross
      sectional, analytical study included 89 children aged 6-12 years in outpatient
      follow-up: 27 healthy (H), 31 with rhinitis (R), and 31 with mild asthma under
      control (A). Pulmonary function parameters and maximal respiratory pressures were
      measured before and 5, 10, and 30 minutes after the 6MWT. Wilcoxon test was used
      to compare numerical numerical variables between two groups and analysis of
      variance or Kruskal-Wallis test for comparison among three groups. RESULTS: Total
      distance traveled in the 6MWT was similar among the three groups. Compared to pre
      test values, VEF1 (Forced Expiratory Volume in 1 second), VEF0.75 (Forced
      Expiratory Volume in 0.75 second), and FEF25-75 (Forced Expiratory Flow 25-75% of
      the Forced Vital Capacity - CVF - curve) decreased significantly after the 6MWT
      in group A, and VEF0.75, FEF25-75, and VEF1/CVF decreased significantly in group
      R. Groups A and R had lower Maximum Inspiratory Pressure values than group H
      before and after the 6MWT at all time points assessed. CONCLUSIONS: The findings
      suggest that children with rhinitis and mild asthma present with alterations in
      respiratory muscle strength and pulmonary function not associated with clinical
      complaints, reinforcing the concept of the united airways.

PMID- 28488886
TI  - Network support, technology use, depression, and ART adherence among HIV-positive
      MSM of color.
AB  - Depression is associated with poor antiretroviral therapy (ART) adherence among
      people living with HIV/AIDS. This relationship may be moderated by an
      individual's social network characteristics. Our study sought to examine social
      network correlates of treatment adherence among HIV-positive men recruited from
      social service agencies throughout Los Angeles County (N = 150) to inform
      technology-driven social support interventions for this population. We
      administered egocentric social network and computer-assisted survey interviews
      focused on demographic characteristics, health history, depressive symptoms, and
      ART adherence, where adherence was assessed by the number of reasons participants
      missed taking their medication, if ever. Significant univariate correlates of
      adherence were included in a multivariable regression analysis, where the
      moderating effect of having a network member who reminds participants to take
      their HIV medication on the relationship between depression and adherence was
      tested. Over 60% of participants reported clinically significant depressive
      symptoms; this was significantly associated with lower adherence among those
      without someone in their social network to remind them about taking their HIV
      medication, even after adjusting for covariates in an ordinary least squares
      regression (adjusted mean difference b = -1.61, SE = 0.42, p = 0.0003). Having a
      network member who reminds participants to take their ART medication
      significantly ameliorated the negative association between depression and
      treatment adherence, especially for those reporting greater depressive symptoms
      (p = 0.0394). Additionally, participants demonstrated high rates of technology
      use to communicate with social network members. In order to achieve the aims of
      the National HIV/AIDS Strategy, innovative interventions addressing mental health
      to improve ART adherence are needed. Network strategies that leverage technology
      may be helpful for improving ART adherence among HIV-positive men with comorbid
      depressive symptoms.

PMID- 28488887
TI  - Rapid and affordable genome-wide bisulfite DNA sequencing by XmaI-reduced
      representation bisulfite sequencing.
AB  - AIM: To develop a reduced representation bisulfite sequencing (RRBS) approach for
      rapid and affordable genome-wide DNA methylation analysis. METHODS: We have
      selected restriction endonuclease XmaI to produce RRBS library fragments. After
      digestion and partial fill-in DNA fragments were ligated to barcoded adapters,
      bisulfite converted, size-selected, and sequenced on the Ion Torrent Personal
      Genome Machine. XmaI-RRBS results were compared with the previously published
      RRBS data. RESULTS: We have developed an XmaI-RRBS method for rapid and
      affordable genome-wide DNA methylation analysis, with library preparation taking
      only 4 days and sequencing possible within 4 h. We have also addressed several
      challenges in order to further improve the RRBS technology. XmaI-RRBS may be
      performed on degraded DNA samples and is compatible with the bench-top next
      generation sequencing machines.

PMID- 28488888
TI  - Reply to: Uric Acid and Contrast-Induced Nephropathy: Diagnostic Marker,
      Therapeutic Target, or Innocent Bystander?

PMID- 28488889
TI  - Experiencing place: Younger people with dementia facing aged care.
AB  - OBJECTIVES: There are currently few facilities for people with younger onset
      dementia and they are placed by default into dementia care facilities designed
      for the elderly. There is limited understanding of how people with younger onset
      dementia and their care givers anticipate or experience aged residential care.
      This qualitative study has used semi-structured interviews to give voice to the
      opinions and perspectives of nine people with younger onset dementia and 11 care
      givers. METHOD: Interpretative Phenomenological Analysis was used for idiographic
      analysis, allowing examination of the lived experience of younger people with
      dementia and an iterative exploration of what their experiences mean. RESULTS:
      Themes of memory, autonomy and therapy emerged from the data. There is a need for
      a familiar memory of place in an intergenerational community and home-like
      setting. The loss of autonomy and ensuing stagnation or even institutional
      internment was much feared. Appropriate exercise and purposeful occupational
      activities as well as emotional support were valued therapies but often lacking
      for this group Conclusions: Emotional distress with the loss of a meaningful life
      can result from the placement of younger people with dementia into old age
      services. Development of age-appropriate services are required.

PMID- 28488890
TI  - Exploring experiences of and attitudes towards mental illness and disclosure
      amongst health care professionals: a qualitative study.
AB  - BACKGROUND: The literature suggests that many health professionals hold
      stigmatising attitudes towards those with mental illness and that this impacts on
      patient care. Little attention has been given to how these attitudes affect
      colleagues with a mental illness. Current research demonstrates that stigma and
      discrimination are common in the UK workplace and impact on one's decision to
      disclose mental illness. AIMS: This study aims to explore health professionals'
      experiences of and attitudes towards mental illness and disclosure in the
      workplace. METHODS: This qualitative study involved semi-structured interviews
      with 24 health professionals employed by an NHS (National Health Service) trust.
      13 of these worked in mental health, and 11 in other health fields. Interviews
      were transcribed and thematic analysis was used to identify themes. RESULTS: Five
      key themes were identified from the data: personal experiences and their effect
      in changing attitudes; perceived stigmatising views of mental illness in other
      staff members; hypothetical disclosure: factors affecting one's decision;
      attitudes towards disclosure; support in the workplace after disclosure; and,
      applying only to those working outside of the mental health field, mental illness
      is not talked about. The results indicated that participants had a great deal of
      experience with colleagues with a mental illness and that support in the
      workplace for such illnesses is variable. Attitudes of participating health
      professionals towards colleagues with a mental illness appeared to be positive,
      however, they did report that other colleagues held negative attitudes. Deciding
      to disclose a mental illness was a carefully thought out decision with a number
      of advantages and disadvantages noted. In particular, it was found that health
      professionals' fear stigma and discrimination from colleagues and that this would
      dissuade participants from disclosing a mental illness. CONCLUSION: In many
      respects, this research supports the findings in other workplaces. Such findings
      need to be investigated further to identify the degree to which these experiences
      and attitudes can be applied to other health professionals in other healthcare
      settings to determine what intervention is necessary. Importantly, this study has
      also indicated that the level of support available to NHS health professionals
      with a mental illness is variable, suggesting the need to identify and replicate
      positive practice.

PMID- 28488891
TI  - Missed Initial Medical Visits: Predictors, Timing, and Implications for Retention
      in HIV Care.
AB  - HIV disproportionately affects racial/ethnic minorities and individuals living in
      the southern United States, and missed clinic visits account for much of this
      disparity. We sought to evaluate: (1) predictors of missed initial HIV medical
      visits, (2) time to initial visit, and (3) the association between initial visit
      attendance and retention in HIV care. Chart reviews were conducted for 200
      consecutive HIV-infected patients (100 in Dallas, 100 in San Antonio) completing
      case management (CM) intake. Of these, 52 (26%) missed their initial visit, with
      22 (11%) never presenting for care. Mean age was 40 years, 85% were men, >70%
      were of minority race/ethnicity, and 28% had a new HIV diagnosis. Unemployment
      (OR [95% CI] = 2.33 [1.04-5.24], p = 0.04) and lower attendance of CM visits (OR
      = 3.08 [1.43-6.66], p = 0.004) were associated with missing the initial medical
      visit. A shorter time to visit completion was associated with CD4 <= 200 (HR 1.90
      [1.25-2.88], p = 0.003), Dallas study site (HR = 1.48 [1.03-2.14], p = 0.04), and
      recent hospitalization (HR = 2.18 [1.38-3.43], p < 0.001). Patients who did not
      complete their initial medical visit within 90 days of intake were unlikely to
      engage in care. Initial medical visit attendance was associated with higher
      proportion of visits attended (p = 0.04) and fewer gaps in care (p = 0.01).
      Missed medical visits were common among HIV patients initiating or reinitiating
      care in Texas. Employment and CM involvement predicted initial medical visit
      attendance, which was associated with retention in care. New, early engagement
      strategies are needed to decrease missed visits and reduce HIV health
      disparities.

PMID- 28488892
TI  - Dcp1a and GW182 Induce Distinct Cellular Aggregates and Have Different Effects on
      microRNA Pathway.
AB  - P-bodies are cytoplasmic foci composed of mRNAs and enzymes involved in mRNA
      degradation. P-bodies have been found to link to RNA interference and RNA decay
      mediated by microRNAs (miRNAs) and translational repression. Here, we aim to
      investigate different effects of overexpressed Dcp1a or GW182 on cytoplasmic
      aggregates formation and influence on miRNA pathway. Small RNAs were recruited
      into endogenous foci of P-bodies and aggregates formed by Dcpa1 and GW182
      overexpression. However, only overexpressed Dcp1a but not GW182 was colocalized
      with DDX6, another component of P-bodies and suppressed protein translation. In
      addition, we investigated the relationship between stress granules and miRNA
      pathway and found that granules induced by G3BP1 overexpression could recruit
      small RNAs into the granules and repressed protein translation. As Ago2 is a key
      component of RNA-induced silencing complex, we also investigated the localization
      of endogenous Ago2 (edo-Ago2) after Dcp1a and GW182 overexpression, and found
      that endo-Ago2 did not colocalize with the aggregates induced by overexpression
      of Dcpla, GW182, and G3BP1. Notably, the ability of miRNA to regulate its target
      was enhanced by the granules induced by Dcp1a and G3BP1 expression. Our results
      suggest that overexpressed Dcp1a and GW182 can form different cytoplasmic
      aggregates and play distinct biological roles in the miRNA pathway.

PMID- 28488893
TI  - VDR, RANKL and OPG polymorphisms as possible predisposing cofactors of
      postmenopausal osteoporosis: explorative study in Italian population.
AB  - Postmenopausal osteoporosis (PO) has a strong genetic component. Presently, the
      published evidence on the association between the main single-nucleotide
      polymorphisms (SNPs) of the receptor activator of nuclear factor-kb ligand
      (RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR) and bone mass density
      (BMD) are scarce, mostly considering Italian population. This study sought to
      determine whether OPG (rs2073618), RANKL (rs9525641) and the VDR (rs2228570) SNPs
      were associated with BMD in a sample of 139 North-Italian postmenopausal women.
      The allelic distribution of rs9525641 in women with PO or osteopenia (OP + OPE
      group) differed from controls (p < 0.05), suggesting that this allele might
      confer a greater susceptibility to bone resorption. Concerning rs2228570, CC
      genotype was associated with OP + OPE women, with a worst total hip BMD. Notably,
      the combined genotype RANK (CT)-VDR (TT) was significantly associated to spine
      BMD (p < 0.05). In conclusion, this pilot study showed that rs9525641 and
      rs2228570 polymorphisms might contribute, separately or in combination, in
      determining BMD phenotype in selected postmenopausal populations.

PMID- 28488894
TI  - Development of a UHPLC-MS/MS (SRM) method for the quantitation of endogenous
      glucagon and dosed GLP-1 from human plasma.
AB  - AIM: The performance of glucagon and GLP-1 immunoassays is often poor, but few
      sensitive LC-MS/MS methods exist as alternatives. EXPERIMENTAL: A multiplexed LC
      MS/MS method using a 2D extraction technique was developed. RESULTS: The method
      was established for the quantitation of endogenous glucagon (LLOQ: 15 pg/ml) and
      dosed GLP-1 (LLOQ: 25 pg/ml) in human plasma, and is the first such method
      avoiding immunoenrichment. Specificity of endogenous glucagon quantitation was
      assured using a novel approach with a supercharging mobile phase additive to
      access a sensitive qualifier SRM. Endogenous glucagon concentrations were within
      the expected range, and showed good reproducibility after extended sample
      storage. A cross-validation against established immunoassays using physiological
      study samples demonstrated some similarities between methods. CONCLUSION: The LC
      MS/MS method offers a viable alternative to immunoassays for quantitation of
      endogenous glucagon, dosed glucagon and/or dosed GLP-1.

PMID- 28488895
TI  - Sleep quality, chronotype, temperament and bipolar features as predictors of
      depressive symptoms among medical students.
AB  - The assessment of risk factors is a crucial step in the prevention and treatment
      of affective disorders and should encompass personal dispositions. The aim of
      this study was to assess the value of chronotype and temperament as independent
      predictors of depressive symptoms among medical students. The study surveyed 140
      students of the Faculty of Medicine with a battery of questionnaires: the Beck
      Depression Index (BDI), Hypomania Checklist 32 (HCL-32), Pittsburgh Sleep Quality
      Index (PSQI), Chronotype Questionnaire and Eysenck Personality Questionnaire
      Revised. The results were tested using Pearson's correlation quotient and general
      linear model. Ten percent of the participants demonstrated a BDI score suggestive
      of clinically significant depressive symptoms. BDI score correlated positively
      with HCL-32 score. A rise in BDI was independently predicted by elevated
      Neuroticism and PSQI scores and morningness. Those effects were independent from
      each other and from other parameters of the model. The presence of depressive
      symptoms might be associated with bipolar features among medical students. Poor
      sleep quality predicted depressive symptoms, similarly to Neuroticism and
      independently of temperament and chronotype. Future studies on the associations
      between personal dispositions and mood disorders among medical students are
      required to help identify those at greater risk of developing affective illness.
      Effective prophylaxis and early intervention are warranted to ensure better
      treatment results.

PMID- 28488896
TI  - A sensitive assay for ZYAN1 in human whole blood and urine utilizing positive LC
      MS/MS electrospray ionization.
AB  - AIM: A sensitive LC-MS/MS method was developed and validated for estimation of
      ZYAN1 in human blood/urine. METHODS: An analog internal standard IOX2 along with
      ZYAN1 was quantified using selective reaction monitoring in positive mode. The
      chromatographic separation was performed by gradient elution with C18 analytical
      column (3 um, 50 mm * 2.0 mm) with 4-min run time using an acidified mobile phase
      consisting of ammonium formate and acetonitrile. Protein precipitation enabled
      extraction of analytes from diluted blood/urine. RESULTS: Calibration curve of
      ZYAN1 was linear (2-5000 ng/ml). The recovery of ZYAN1 and IOX2 was between 87
      and 104%. Interday and intraday accuracy and precision was found well within the
      acceptance criteria. CONCLUSION: The validated assay was applied for clinical
      pharmacokinetics of ZYAN1 in healthy volunteers.

PMID- 28488897
TI  - Mediation, moderation, and context: Understanding complex relations among
      cognition, affect, and health behaviour.
AB  - OBJECTIVE: Researchers have historically treated cognition and affect as separate
      constructs in motivating health behaviour. We present a framework and empirical
      evidence for complex relations between cognition and affect in predicting health
      behaviour. Main Outcome, Design and Results: First, affect and cognition can
      mediate each other's relation to health behaviour. Second, affect and cognition
      can moderate the other's impact. Third, context can change the interplay of
      affect and cognition. Fourth, affect and cognition may be indelibly fused in some
      psychological constructs (e.g. worry, anticipated regret and reactance). These
      four propositions in our framework are not mutually exclusive. CONCLUSION:
      Examination of the types of complex relations described here can benefit theory
      development, empirical testing of theories and intervention design. Doing so will
      advance the understanding of mechanisms involved in regulation of health
      behaviours and the effectiveness of interventions to change health behaviours.

PMID- 28488898
TI  - Bridging immunogenicity assays for IgG4 therapeutics: mitigating interference
      from Fc-Fc interactions.
AB  - AIM: A bridging immunogenicity assay for a human IgG4 mAb therapeutic was
      transferred to an automation system to increase throughput. However, background
      signal increased five- to six-fold during the 6- to 8-h run. RESULTS: Noncovalent
      Fc contacts formed between labeled IgG4 drugs in reagent solutions stored during
      the automation run. This generated substantial background signal, reducing assay
      sensitivity by approximately sixfold. Fc interactions also significantly impacted
      the confirmation assay. Fc contacts formed between labeled and unlabeled drug,
      significantly increasing signal inhibition (~7-70%) in the 6-h run. CONCLUSION:
      Storing labeled antibody solutions separately and combining them immediately
      before adding to samples reduced interference from Fc interactions. Preincubation
      time for reagent solutions should be strictly controlled for anti-drug antibody
      assays with IgG4 drugs to avoid false-positive results.

PMID- 28488899
TI  - Lifetime prevalence of psychiatric morbidities, suicidality, and quality of life
      in a community population with the bimodal chronotype: A nationwide epidemiologic
      study.
AB  - Chronotypes are classified as morning, evening, or intermediate, but there are
      reports of a bimodal type. This study was undertaken to describe the
      characteristics of the bimodal chronotype and to explore relationships between
      the bimodal type and psychiatric disorders, fatigue, and quality of life. A total
      of 2389 subjects from a Korean national epidemiological survey of psychiatric
      disorders responded during face-to-face interviews. The Korean Composite
      International Diagnostic Interview was used to diagnose psychiatric disorders,
      and the Composite Scale of Morningness was used to assess chronotypes. Among
      intermediate-type subjects, those with a positive bimodal index were classified
      as bimodal type. In the present study, the proportions of bimodal, morning,
      intermediate, and evening types were 4.8%, 10.8%, 73.3%, and 11.1%, respectively.
      Distributions of sociodemographic variables were similar for the bimodal and
      intermediate types. After controlling for sociodemographic variables, any mood
      disorder and major depressive disorder were found to be significantly more
      associated with the bimodal type than the morning type, and dysthymic disorder
      was significantly more associated with the bimodal type than the intermediate
      type. For quality-of-life domains, moderate or extreme pain/discomfort was
      complained about more by subjects with the bimodal type than other types. In
      summary, the study shows chronotypes differ with respect to their relationships
      with mood disorder and quality of life. Before the bimodal type is classified as
      a clinically valid type, further investigations are needed to examine its
      psychological, physiological, and genetic characteristics.

PMID- 28488900
TI  - Isolated polyhydramnios in the third trimester: is a gestational diabetes
      evaluation of value?
AB  - We evaluated implications of testing for gestational diabetes mellitus (GDM) in
      pregnancies complicated by third trimester isolated polyhydramnios with previous
      negative diabetes screening test. In this retrospective cohort study of 104
      pregnant women with polyhydramnios between 2005 and 2013, all had normal first
      trimester fasting glucose and normal glucose challenge test (GCT < 140 mg/dL).
      Late onset GDM was diagnosed in five women (4.8%) with isolated polyhydramnios,
      one abnormal value in the oral glucose tolerance test (OGTT) was identified in
      four additional women (3.8%). No significant differences were found in risk
      factors for GDM, mean second trimester GCT (117.5 vs. 107.2 mg/dL, p = 0.38) or
      fasting glucose values (82 vs. 86 mg/dL, p = 0.29) between women in the
      polyhydramnios group with and without late GDM diagnosis. Moreover, no
      significant difference was found in relation to the mode of delivery or birth
      weight between the studied groups (3437 +/- 611 vs. 3331 +/- 515 g, p = 0.63).
      Diagnosis of third trimester polyhydramnios was not associated with increased
      risk for GDM or neonatal complications.

PMID- 28488901
TI  - Association of shiftwork and immune cells among police officers from the Buffalo
      Cardio-Metabolic Occupational Police Stress study.
AB  - Shift workers suffer from a constellation of symptoms associated with disruption
      of circadian rhythms including sleep abnormalities, and abnormal hormone
      secretion (e.g. melatonin, cortisol). Recent, but limited, evidence suggests that
      shift workers have elevated levels of circulating white blood cells (WBCs)
      compared to their day working counterparts. Interestingly, recent reviews
      highlight the strong linkage between the immune system and circadian rhythms
      which includes, but is not limited to, circulating cell populations and
      functions. The elevated levels of these WBCs may be associated with the increased
      chronic disease risk observed among this group. The purpose of this analysis was
      to examine the cross-sectional association between long- and short-term (3, 5, 7,
      and 14 days) shiftwork (SW) and counts of WBCs among officers in the Buffalo
      Cardio-Metabolic Occupational Police Stress (BCOPS) cohort. Data collection for
      this analysis took place among 464 police officers working in Buffalo, New York,
      USA between 2004 and 2009. Precise SW histories were obtained using electronic
      payroll records. Officers were assigned a shift type based on the shift (i.e.
      day, evening, night) that they spent a majority (i.e. >=50%) of their time from
      1994 to the data collection date for long-term SW. The same process was applied
      to SW over 3, 5, 7, and 14 days prior to data collection. A fasted blood sample
      collected in the morning of a non-work day was used for characterization of WBCs
      (total), neutrophils, monocytes, lymphocytes, eosinophils, and basophils.
      Potential confounding factors included demographic characteristics (e.g. age,
      sex, race), occupational characteristics (e.g. rank), health behaviors (e.g.
      smoking, alcohol consumption, diet), anthropometrics, and other biomarkers (e.g.
      lipids, hemoglobin A1C, leptin). Generalized linear models were used to estimate
      least square means of the immune cells according to SW categorization for long-
      and short-term SW histories. Compared to the day shift group, those working long
      term night shifts had greater absolute numbers of total WBCs, neutrophils,
      lymphocytes, and monocytes (all p < 0.05). Those working mainly on the night
      shift over 7-days had elevated counts of WBCs, lymphocytes, and monocytes (p <
      0.05) compared to those mainly working day shifts. Results based on 3-, 5-, and
      14-day SW were similar to the 7-day results. This study corroborates other
      studies with similar findings. However, this analysis provided insights into the
      effect of both long- and short-term SW on the number of circulating WBCs. SW may
      lead to disruption of circadian-influenced components of the immune system, which
      in term, may result in various chronic diseases. These findings, plus previous
      findings, may provide evidence that SW may lead to immune system dysregulation.
      Future research is needed to understand whether increases in immune cells among
      shift workers may be associated with the increased disease risk among this group.

PMID- 28488902
TI  - Designing augmentative and alternative communication applications: the results of
      focus groups with speech-language pathologists and parents of children with
      autism spectrum disorder.
AB  - PURPOSE: The purpose of this study was to gain insight from speech-language
      pathologists (SLPs) and parents of children with autism spectrum disorder (ASD)
      regarding appealing features of augmentative and alternative communication (AAC)
      applications. METHOD: Two separate 1-hour focus groups were conducted with 8 SLPs
      and 5 parents of children with ASD to identify appealing design features of AAC
      Apps, their benefits and potential concerns. Participants were shown novel
      interface designs for communication mode, play mode and incentive systems.
      Participants responded to poll questions and provided benefits and drawbacks of
      the features as part of structured discussion. RESULTS: SLPs and parents
      identified a range of appealing features in communication mode (customization,
      animation and colour-coding) as well as in play mode (games and videos). SLPs
      preferred interfaces that supported motor planning and instruction while parents
      preferred those features such as character assistants that would appeal to their
      child. Overall SLPs and parents agreed on features for future AAC Apps.
      CONCLUSION: SLPs and parents have valuable input in regards to future AAC app
      design informed by their experiences with children with ASD. Both groups are key
      stakeholders in the design process and should be included in future design and
      research endeavors. Implications for Rehabilitation AAC applications for the iPad
      are often designed based on previous devices without consideration of new
      features. Ensuring the design of new interfaces are appealing and beneficial for
      children with ASD can potentially further support their communication. This study
      demonstrates how key stakeholders in AAC including speech language pathologists
      and parents can provide information to support the development of future AAC
      interface designs. Key stakeholders may be an untapped resource in the
      development of future AAC interfaces for children with ASD.

PMID- 28488903
TI  - Versican A-subdomain is required for its adequate function in dermal development.
AB  - Versican, a large chondroitin sulfate (CS) proteoglycan, serves as a structural
      macromolecule of the extracellular matrix (ECM) and regulates cell behavior. We
      determined the function of versican in dermal development using VcanDelta3/Delta3
      mutant mice expressing versican with deleted A-subdomain of the N-terminal G1
      domain. The mutant versican showed a decreased hyaluronan (HA)-binding ability
      and failed to accumulate in the ECM. In the early developmental stage,
      VcanDelta3/Delta3 dermis showed a decrease in versican expression as compared
      with WT. As development proceeded, versican expression further decreased to a
      barely detectable level, and VcanDelta3/Delta3 mice died at the neonatal period
      (P0). At P0, VcanDelta3/Delta3 dermis exhibited an impaired ECM structure and
      decreased cell density. While the level of collagen deposition was similar in
      both genotypes, collagen biosynthesis significantly decreased in
      VcanDelta3/Delta3 fibroblasts as compared with that in wild type (WT).
      Transforming growth factor beta (TGFbeta) signaling mediated through the Smad2/3
      dependent pathway was down-regulated in VcanDelta3/Delta3 fibroblasts and a
      reduced TGFbeta storage in the ECM was observed. Microarray analysis revealed a
      decrease in the expression levels of transcription factors, early growth response
      (Egr) 2 and 4, which act downstream of TGFbeta signaling. Thus, our results
      suggest that A-subdomain is necessary for adequate versican expression in dermis
      and that versican is involved in the formation of the ECM and regulation of
      TGFbeta signaling.

PMID- 28488904
TI  - Use of an Outreach Coordinator to Reengage and Retain Patients with HIV in Care.
AB  - It is well established that retention in high-quality care and regular visits
      with an HIV/AIDS provider improve outcomes for people living with HIV/AIDS
      (PLWHA). However, nationally and regionally in South Carolina, retention rates
      remain low. We piloted an outreach program focused on characterizing out of care
      (OOC) patients to identify PLWHA who were lost to care and attempt reengagement
      through phone call, letter, and home visit interventions. Primary outcomes were
      reengagement, defined as attendance to a clinic appointment, and retention in
      care, defined by the Health Resources and Services Administration (HRSA)
      definition (two visits at least 90 days apart in 2015). There were 1242 adult
      clinic patients in 2014. A total of 233 patients were included in the OOC cohort,
      according to the inclusion criteria. Of these 233, the outreach coordinator found
      that a majority of patients, 119 (51%), were lost to care. Reengagement was seen
      in 52 (44%) patients lost to care, and among those who reengaged, 26 (50%) were
      retained in care in 2015. This report represents one of few interventions that
      target reengagement for patients who are lost to care. The use of an outreach
      coordinator was successful in reengaging and retaining patients in care. It
      represents an uncomplicated intervention, functional within the current clinic
      design and available funding structure of the Ryan White grant. Poor engagement
      and retention in care continue to be significant problems among PLWHA with
      resultant poor clinical outcomes. Continued focus on new interventions to improve
      retention in care is necessary to improve clinical outcomes.

PMID- 28488905
TI  - Tactical Behaviors in Men's 800-m Olympic and World-Championship Medalists: A
      Changing of the Guard.
AB  - PURPOSE: To assess the longitudinal evolution of tactical behaviors used to medal
      in men's 800-m Olympic Games (OG) or world-championship (WC) events in the recent
      competition era (2000-2016). METHODS: Thirteen OG and WC events were
      characterized for 1st- and 2nd-lap splits using available footage from YouTube.
      Positive pacing strategies were defined as a faster 1st lap. Season's best 800-m
      time and world ranking, reflective of an athlete's "peak condition," were
      obtained to determine relationships between adopted tactics and physical
      condition prior to the championships. Seven championship events provided coverage
      of all medalists to enable determination of average 100-m speed and sector pacing
      of medalists. RESULTS: From 2011 onward, 800-m OG and WC medalists showed a
      faster 1st lap by 2.2 +/- 1.1 s (mean, +/-90% confidence limits; large
      difference, very likely), contrasting a possibly faster 2nd lap from 2000 to 2009
      (0.5, +/-0.4 s; moderate difference). A positive pacing strategy was related to a
      higher world ranking prior to the championships (r = .94, .84-.98; extremely
      large, most likely). After 2011, the fastest 100-m sector from 800-m OG and WC
      medalists was faster than before 2009 by 0.5, +/-0.2 m/s (large difference, most
      likely). CONCLUSIONS: A secular change in tactical racing behavior appears
      evident in 800-m championships; since 2011, medalists have largely run faster 1st
      laps and have faster 100-m sector-speed requirements. This finding may be
      pertinent for training, tactical preparation, and talent identification of
      athletes preparing for 800-m running at OGs and WCs.

PMID- 28488906
TI  - Factors Affecting Match Outcome in Elite Australian Football: A 14-Year Analysis.
AB  - Effects of fixture and team characteristics on match outcome in elite Australian
      football were quantified using data accessed at AFLtables.com for 5109 matches
      for seasons 2000 to 2013. Aspects of each match included number of days' break
      between matches (<=7 d vs >=8 d), location (home vs away), travel status (travel
      vs no travel), and differences between opposing teams' mean age, body mass, and
      height (expressed as quintiles). A logistic-regression version of the generalized
      mixed linear model estimated each effect, which was assessed with magnitude-based
      inference using 1 extra win or loss in every 10 matches as the smallest important
      change. For every 10 matches played, the effects were days' break, 0.1 +/- 0.3
      (90% CL) wins; playing away, 1.5 +/- 0.6 losses; traveling, 0.7 +/- 0.6 losses;
      and being in the oldest, heaviest, or shortest, quintile, 1.9 +/- 0.4, 1.3 +/-
      0.4, and 0.4 +/- 0.4 wins, respectively. The effects of age and body-mass
      difference were not reduced substantially when adjusted for each other. All
      effects were clear, mostly at the 99% level. The effects of playing away, travel,
      and age difference were not unexpected, but the trivial effect of days' break and
      the advantage of a heavier team will challenge current notions about balancing
      training with recovery and about team selection.

PMID- 28488907
TI  - Prediction: The Modern-Day Sport-Science and Sports-Medicine "Quest for the Holy
      Grail".
AB  - In high-performance sport, science and medicine practitioners employ a variety of
      physical and psychological tests, training and match monitoring, and injury
      screening tools for a variety of reasons, mainly to predict performance, identify
      talented individuals, and flag when an injury will occur. The ability to
      "predict" outcomes such as performance, talent, or injury is arguably sport
      science and medicine's modern-day equivalent of the "Quest for the Holy Grail."
      The purpose of this invited commentary is to highlight the common
      misinterpretation of studies investigating association to those actually
      analyzing prediction and to provide practitioners with simple recommendations to
      quickly distinguish between methods pertaining to association and those of
      prediction.

PMID- 28488908
TI  - Choosing, Doing, and Controlling: Implicit Sense of Agency Over Somatosensory
      Events.
AB  - Sense of agency-a feeling of control over one's actions and their outcomes-might
      include at least two components: free choice over which outcome to pursue and
      motoric control over the action causing the outcome. We orthogonally manipulated
      locus of outcome choice (free or instructed choice) and motoric control (active
      or passive movement), while measuring the perceived temporal attraction between
      actions and outcomes ( temporal binding) as an implicit marker of agency.
      Participants also rated stimulus intensity so that we could measure sensory
      attenuation, another possible implicit marker of agency. Actions caused higher or
      lower levels of either painful heat or mild electrotactile stimulation. We found
      that both motoric control and outcome choice contributed to outcome binding.
      Moreover, free choice, relative to instructed choice, attenuated the perceived
      magnitude of high-intensity outcomes, but only when participants made an active
      movement. Thus, choosing, not just doing, influences temporal binding and sensory
      attenuation, though in different ways. Our results show that these implicit
      measures of agency are sensitive to both voluntary motor commands and
      instrumental control over action outcomes.

PMID- 28488909
TI  - First episode indices associated with lifetime chronicity of depression among
      formerly depressed participants: an exploratory study.
AB  - BACKGROUND: Researchers have found that an earlier age of disorder onset and the
      severity of the first depressive episode are associated with recurrence in
      depression. Additionally, neuroticism has been shown to be an important factor in
      the recurrence of the disorder. AIMS: This exploratory study aimed to replicate
      and extend previous research by examining the relationships between features of
      the first experienced depressive episode (age of onset, severity), the five
      factors of personality, and lifetime chronicity of depression. METHOD: Forty
      three previously depressed participants completed measures of personality,
      current depression, hopelessness, and perfectionism. Previous depressive episodes
      were assessed using a semi-structured interview, and features of these episodes
      experienced by participants were recorded. RESULTS: Pearson correlations showed
      that depression chronicity, measured in the number of weeks depressed in a
      lifetime, was significantly correlated with age of onset and number of symptoms
      experienced in the first episode. Personality measures were not significantly
      associated with depression chronicity. CONCLUSION: Earlier and more severe first
      episodes of depression may play an important role in the recurrence of the
      disorder. Future research should focus on replication and determining the causal
      role of these features.

PMID- 28488910
TI  - Methadone-Induced Neurotoxicity in Advanced Cancer: A Case Report.
AB  - Methadone use as a second-line agent for severe cancer-related pain is increasing
      in the field of hospice and palliative care. It has a number of qualities that
      make its use favorable, including lack of known active metabolites and presumed
      relative safety from adverse effects such as opioid-induced neurotoxicity (OIN).
      This article describes a case of a patient undergoing treatment of severe cancer
      related pain who developed OIN in the setting of oral methadone use. As the use
      of methadone increases, more research into its pharmacologic and pharmacokinetic
      properties will be necessary.

PMID- 28488911
TI  - Comparison Between Video-Assisted and Open Lateral Neck Dissection for Papillary
      Thyroid Carcinoma with Lateral Neck Lymph Node Metastasis: A Prospective
      Randomized Study.
AB  - BACKGROUND: The safety and oncologic completeness of video-assisted lateral neck
      dissection (VALND) for papillary thyroid carcinoma (PTC) with lateral neck lymph
      node metastasis (LNM) have been reported. However, their generalization has
      remained limited because the advantages and drawbacks are not well demonstrated.
      MATERIALS AND METHODS: A total of 64 patients with PTC and unilateral lateral
      neck LNM who underwent total thyroidectomy with central compartment neck
      dissection and lateral neck dissection (LND) were prospectively enrolled. They
      were randomly assigned to the video-assisted (VA) group (n = 32) or open group (n
      = 32) and were treated either by VALND or conventional open LND, respectively. We
      compared operating time, complications, oncologic completeness, postoperative
      pain, and cosmetic results between the two groups. RESULTS: The complication rate
      and oncologic completeness, including the results of radioactive iodine scans,
      mean number of lymph nodes retrieved, and mean postoperative serum thyroglobulin
      levels, were similar between the groups. Postoperative pain was observed less
      frequently after surgery in the VA group (P < .0001). Cosmetic results evaluated
      by a verbal response scale and a numeric rating scale were in favor of the VA
      group (P < .0001 and P = .0004, respectively). Total operating time was 176 +/-
      16 minutes in the VA group and 161 +/- 16 minutes in the open group (P = .0003).
      CONCLUSIONS: VALND yielded complication and oncologic completeness rates that
      were similar to those of open LND. However, VALND resulted in less postoperative
      pain and better cosmetic results.

PMID- 28488913
TI  - Relationship Between Pretraining Subjective Wellness Measures, Player Load, and
      Rating-of-Perceived-Exertion Training Load in American College Football.
AB  - CONTEXT: The relationship between pretraining subjective wellness and external
      and internal training load in American college football is unclear. PURPOSE: To
      examine the relationship of pretraining subjective wellness (sleep quality,
      muscle soreness, energy, wellness Z score) with player load and session rating of
      perceived exertion (s-RPE-TL) in American college football players. METHODS:
      Subjective wellness (measured using 5-point, Likert-scale questionnaires),
      external load (derived from GPS and accelerometry), and s-RPE-TL were collected
      during 3 typical training sessions per week for the second half of an American
      college football season (8 wk). The relationship of pretraining subjective
      wellness with player load and s-RPE training load was analyzed using linear mixed
      models with a random intercept for athlete and a random slope for training
      session. Standardized mean differences (SMDs) denote the effect magnitude.
      RESULTS: A 1-unit increase in wellness Z score and energy was associated with
      trivial 2.3% (90% confidence interval [CI] 0.5, 4.2; SMD 0.12) and 2.6% (90% CI
      0.1, 5.2; SMD 0.13) increases in player load, respectively. A 1-unit increase in
      muscle soreness (players felt less sore) corresponded to a trivial 4.4% (90% CI 
      8.4, -0.3; SMD -0.05) decrease in s-RPE training load. CONCLUSION: Measuring
      pretraining subjective wellness may provide information about players' capacity
      to perform in a training session and could be a key determinant of their response
      to the imposed training demands American college football. Hence, monitoring
      subjective wellness may aid in the individualization of training prescription in
      American college football players.

PMID- 28488912
TI  - A high level of estrogen-stimulated proteins selects breast cancer patients
      treated with adjuvant endocrine therapy with good prognosis.
AB  - BACKGROUND: Adjuvant endocrine therapy has significantly improved survival of
      estrogen receptor alpha (ER)-positive breast cancer patients, but around 20%
      relapse within 10 years. High expression of ER-stimulated proteins like
      progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I (IGF
      IR) is a marker for estrogen-driven cell growth. Therefore, patients with high
      tumor levels of these proteins may have particularly good prognosis following
      adjuvant endocrine therapy. PATIENTS AND METHODS: Archival tumor tissue was
      available from 1323 of 1396 Danish breast cancer patients enrolled in BIG 1-98, a
      randomized phase-III clinical trial comparing adjuvant letrozole, tamoxifen or a
      sequence of the two drugs. Immunohistochemical staining for ER, HER-2, PR, Bcl-2
      and IGF-IR was performed and determined by Allred scoring (ER, PR and Bcl-2) or
      HercepTest (HER-2 and IGF-IR). RESULTS: Data on all five markers were available
      from 969 patients with ER-positive, HER-2-negative tumors. These patients were
      classified in ER activity groups based on the level of PR, Bcl-2 and IGF-IR. High
      ER activity profile was found in 102 patients (10.5%) and compared with the
      remaining patients, univariate and multivariate analysis revealed HR (95% CI) and
      p values for disease-free survival (DFS) of 2.00 (1.20-3.22), 0.008 and 1.70
      (1.01-2.84), 0.04 and for the overall survival (OS) of 2.33 (1.19-4.57), 0.01 and
      1.90 (0.97-3.79), 0.06, respectively. The high ER activity profile did not
      disclose difference in DFS or OS according to treatment with tamoxifen or
      letrozole (p = .06 and .09, respectively). CONCLUSIONS: Stratifying endocrine
      treated patients in ER activity profile groups disclosed that patient with high
      ER activity profile (10.5%) had significantly longer DFS and OS, and the profile
      was an independent marker for DFS. High ER activity is a marker for estrogen
      driven tumor growth. We suggest further analyses to disclose whether the ER
      activity profile or other markers associated with estrogen-driven growth may be
      used to identify ER-positive high-risk breast cancer patients who can be spared
      adjuvant chemotherapy.

PMID- 28488914
TI  - Decitabine treatment of multiple extramedullary acute myeloid leukemia
      involvements after essential thrombocytemia transformation.

PMID- 28488915
TI  - Unilateral Recession-Resection Surgery for Infantile Esotropia: Survival of Motor
      Outcomes and Postoperative Drifts.
AB  - PURPOSE: To outline the short- and long-term motor outcomes of unilateral medial
      rectus muscle recession and lateral rectus muscle resection for the correction of
      moderate angle infantile esotropia. METHODS: A retrospective study of 109
      consecutive patients with moderate angle infantile esotropia treated with graded
      unilateral recession-resection surgery. Criteria for successful motor outcome
      included alignment +/-10Delta from orthophoria. Outcome evaluation was a
      comparison of successful alignment versus an overcorrection or undercorrection at
      eight weeks postoperatively as well as on the final follow-up examination.
      RESULTS: The mean preoperative deviation was 35.5 prism diopters (Delta) and mean
      follow-up time was 4.9 years. At the eight-week postoperative examination, 99
      patients (89.9%) were successfully aligned, as opposed to 75 of 95 patients
      (78.9%) at the final postoperative visit (P=0.041). There was no statistically
      significant difference between the rate of early versus late undercorrections
      (7.3% versus 12.5%, P=0.267) or overcorrections (2.7% versus 8.3%, P=0.125). Ten
      patients had an esotropic drift over time and 10 patients had an exotropic drift.
      Recurrent esotropia was associated with high hyperopia and presumed infantile
      esotropia diagnostic entity. The Kaplan-Meier estimate of survivorship of a
      successful motor outcome was 75.5% at five years and 71% at 15 years
      postoperatively. The mean response to surgery was 2.9Delta per mm of muscle
      recessed and resected and was positively related to the preoperative angle of
      deviation (R=0.615). CONCLUSIONS: The unilateral recession-resection procedure
      for the correction of infantile esotropia is shown to be associated with a
      favorable survival of motor outcomes and a relatively balanced rate of
      undercorrections versus overcorrections tending to be maintained through the
      follow-up period.

PMID- 28488916
TI  - Observing the fate of tRNA and its modifications by nucleic acid isotope labeling
      mass spectrometry: NAIL-MS.
AB  - RNA in yeast, especially rRNA and tRNA are heavily modified to fulfill their
      function in protein translation. Using biosynthetic stable isotope labeled
      internal standards we quantified 12 modified nucleosides in tRNA from S.
      cerevisiae over 24 hours. We observed different quantities of modified
      nucleosides in dependence of the growth phase. To elucidate the underlying
      mechanism of the observed tRNA modification profile adaptation, it is necessary
      to distinguish the pre-existing tRNA pool and its modifications from newly
      synthesized tRNAs. By combination of 2 differentially isotope labeled media we
      developed NAIL-MS, nucleic acid isotope labeling coupled mass spectrometry.
      During the yeast growth cycle we observe dilution of pre-existing tRNAs by newly
      synthesized tRNAs by the growing number of cells. tRNA was found to be highly
      stable with only little degradation over the observed period. The method was
      further used to quantify the levels of modified nucleosides in the original and
      new tRNA pools. By addition of deuterium-labeled methionine, we could observe the
      incorporation of new methyl marks on pre-existing tRNAs. For 2'-O-methylcytidine
      (Cm) we observed a global increase in log phase. We identified extensive 2'-OH
      cytidine methylation of the pre-existing tRNAs and the new tRNAs which masks an
      actual decrease of pre-existing Cm. In contrast, global 5-methylcytidine (m5C)
      levels decreased during growth due to a drop in m5C quantities in the original
      tRNA pool. The NAIL-MS data suggests different mechanisms for tRNA modification
      adaptation depending on the individual modification observed. With this new tool
      it is possible to follow the fate of methylated RNAs during growth and
      potentially compare the impact of different stress conditions on the
      epitranscriptome.

PMID- 28488917
TI  - Contrasting Gender and Combat Versus Military Sexual Traumas: Psychiatric Symptom
      Severity and Morbidities in Treatment-Seeking Veterans.
AB  - BACKGROUND: Military sexual trauma (MST) and military combat trauma (MCT) are
      significant risk factors for posttraumatic stress disorder (PTSD). However, no
      studies have directly contrasted the clinical profiles of Veterans between
      military-related traumas. Moreover, a notable gender difference in the likelihood
      of trauma exposure limits our ability to disentangle gender and trauma type.
      MATERIALS AND METHODS: To address these gaps, we aimed at (1) contrasting
      psychiatric complaints in Veterans with MST versus MCT exposure and (2)
      investigating gender differences in Veterans with MST histories. Treatment
      seeking Veterans (N = 563) completed semi-structured diagnostic interviews and
      self-report assessments of PTSD, depressive, and dissociative symptoms. RESULTS:
      Psychiatric complaints and morbidity were notable after all military-associated
      traumas, although those seeking care for MST-related events demonstrated more
      severe PTSD, depressive, and dissociative symptoms and were more likely to meet
      criteria for non-PTSD anxiety and psychotic disorders. In contrast, few gender
      related differences were noted between male and female Veterans with histories of
      MST. CONCLUSIONS: The experience of MST may reduce typically observed gender
      related buffering effects for certain conditions.

PMID- 28488918
TI  - The Relationship Between Variables in Wearable Microtechnology Devices and
      Cricket Fast-Bowling Intensity.
AB  - To date, the monitoring of fast-bowling workloads across training and competition
      environments has been limited to counting total balls bowled. However, bowling at
      faster velocities is likely to require greater effort while also placing greater
      load on the bowler. This study investigated the relationship between prescribed
      effort and microtechnology outputs in fast bowlers to ascertain whether the
      technology could provide a more refined measure of workload. Twelve high
      performing fast bowlers (mean +/- SD age 20.3 +/- 2.2 y) participated in the
      study. Each bowler bowled 6 balls at prescribed bowling intensities of 60%, 70%,
      85%, and 100%. The relationships between microtechnology outputs, prescribed
      intensity, and ball velocity were determined using polynomial regression. Very
      large relationships were observed between prescribed effort and ball velocity for
      peak PlayerLoadTM (R = .83 +/- .19 and .82 +/- .20). The PlayerLoad across lower
      ranges of prescribed effort exhibited a higher coefficient of variation (CV) (60%
      = 19.0% [17.0-23.0%]), while the CV at higher ranges of prescribed effort was
      lower (100% = 7.3% [6.4-8.5%]). Routinely used wearable microtechnology devices
      offer opportunities to examine workload and intensity in cricket fast bowlers
      outside the normal metrics reported. They offer a useful tool for prescribing and
      monitoring bowling intensity and workload in elite fast bowlers.

PMID- 28488919
TI  - Nuanced aesthetic emotions: emotion differentiation is related to knowledge of
      the arts and curiosity.
AB  - The ability to distinguish between emotions is considered indicative of well
      being, but does emotion differentiation (ED) in an aesthetic context also reflect
      deeper and more knowledgeable aesthetic experiences? Here we examine whether
      positive and negative ED in response to artistic stimuli reflects higher fluency
      in an aesthetic domain. Particularly, we test whether knowledge of the arts and
      curiosity are associated with more fine-grained positive and negative aesthetic
      experiences. A sample of 214 people rated their positive and negative feelings in
      response to various artworks including positive and negative themes. Positive ED
      was associated with the embracing sub-trait of curiosity that reflects engagement
      and enjoyment of novelty and complexity, but was unrelated to artistic knowledge
      and perceived comprehension. Negative ED was associated with higher curiosity and
      particularly more knowledge of the arts. This relationship was mediated by
      appraised comprehension suggesting that deeper engagement with art, by those with
      more art knowledge, is associated with more fine-grained emotional experiences.
      This finding extends ED beyond well-being research and suggests that more nuanced
      emotional experiences are more likely for those with expertise in the arts and
      motivation for exploration.

PMID- 28488920
TI  - Two-Stage Explantation of a Magnetic Lower Esophageal Sphincter Augmentation
      Device Due to Esophageal Erosion.
AB  - INTRODUCTION: Implanting a magnetic lower esophageal sphincter augmentation
      device (LINX, Torax Medical) has become an increasingly common option in the
      surgical management of gastroesophageal reflux disease. As the enthusiasm for
      placing this device increases, experience in the management of device-related
      complications-including erosion-is necessary. METHODS: We report a staged
      approach to LINX removal in a 64-year-old female with symptoms of odynophagia
      secondary to partial erosion of a LINX device into the esophagus. RESULTS: The
      patient had a 12-bead LINX device placed in 2011 at an outside, international
      facility. In late 2013, she began experiencing symptoms of odynophagia. An
      esophagogastroduodenoscopy at our institution in October 2015 demonstrated two
      metallic beads eroding through the distal esophageal lumen. An elective
      endoscopic removal of the two visible beads was performed. A postoperative
      esophagram confirmed that there was no resulting esophageal perforation. The
      patient noted mild improvement in her symptoms. After a 12-week period to allow
      for complete healing, the remaining 10 beads of the LINX device were explanted
      laparoscopically without complication. No further procedures were undertaken. At
      2 months' follow-up, the patient noted complete resolution of her symptoms.
      CONCLUSION: Transmural erosion of the LINX device into the esophageal lumen is a
      rare occurrence, with only five such complications reported in the published
      literature. We present the first account of LINX explantation for esophageal
      erosion in the United States. We demonstrated that a staged laparoendoscopic
      approach to LINX removal in these cases is feasible with minimal morbidity.

PMID- 28488921
TI  - Sex Differences in World-Record Performance: The Influence of Sport Discipline
      and Competition Duration.
AB  - The current review summarizes scientific knowledge concerning sex differences in
      world-record performance and the influence of sport discipline and competition
      duration. In addition, the way that physiological factors relate to sex
      dimorphism is discussed. While cultural factors played a major role in the rapid
      improvement of performance of women relative to men up until the 1990s, sex
      differences between the world's best athletes in most events have remained
      relatively stable at approximately 8-12%. The exceptions are events in which
      upper-body power is a major contributor, where this difference is more than 12%,
      and ultraendurance swimming, where the gap is now less than 5%. The physiological
      advantages in men include a larger body size with more skeletal-muscle mass, a
      lower percentage of body fat, and greater maximal delivery of anaerobic and
      aerobic energy. The greater strength and anaerobic capacity in men normally
      disappear when normalized for fat-free body mass, whereas the higher hemoglobin
      concentrations lead to 5-10% greater maximal oxygen uptake in men with such
      normalization. The higher percentage of muscle mass in the upper body of men
      results in a particularly large sex difference in power production during upper
      body exercise. While the exercise efficiency of men and women is usually similar,
      women have a better capacity to metabolize fat and demonstrate better
      hydrodynamics and more even pacing, which may be advantageous, in particular
      during long-lasting swimming competitions.

PMID- 28488922
TI  - Predicting prognosis in patients with advanced cancer: A prospective study.
AB  - BACKGROUND: Prognosis is one of the most challenging questions with which
      physicians are confronted. Accuracy in the prediction of survival is necessary
      for clinical, ethical, and organizational reasons. AIM: Evaluate young doctors'
      clinical prediction of survival and the aids they could get: expert opinion,
      Palliative Prognostic score, and Palliative Prognostic Index. DESIGN:
      Prospective, observational study. SETTING/PARTICIPANTS: Advanced cancer patients
      under observation of an inhospital palliative care team, from April to July 2014.
      A total of 38 patients were included, mostly male (65.8%), average age 68.5
      years. Average survival time was 24 days. Follow-up concluded with death or after
      90 days. RESULTS: Young doctors' clinical prediction of survival was adequate at
      10.5%, with 55.3% severe errors in an optimistic direction. Palliative care
      experts were more adequate (23.7%) and made less severe errors (42.1%).
      Palliative Prognostic score and Palliative Prognostic Index were even more
      adequate (47% and 55%, respectively) and made even less severe errors (0% and
      11%, respectively). The best correlation with observed survival was achieved when
      palliative care experts used palliative prognostic score ( rs = -0.629; p <
      0.01). CONCLUSION: Young doctors' clinical prediction of survival is often
      inadequate. Palliative Prognostic score, which includes clinical prediction of
      survival, calculated by palliative care experts had the best performance. Our
      results support the recommendation of using clinical prediction of survival
      together with prognostic scores.

PMID- 28488923
TI  - The effects of life review interventions on spiritual well-being, psychological
      distress, and quality of life in patients with terminal or advanced cancer: A
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Life review interventions have been used to alleviate psycho
      spiritual distress in people near the end of life. However, their effectiveness
      remains inconclusive. AIM: To evaluate the effects of therapeutic life review on
      spiritual well-being, psychological distress, and quality of life in patients
      with terminal or advanced cancer. DESIGN: A systematic review according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology.
      DATA SOURCES: Five databases were searched from their respective inception
      through February 2017 for relevant randomized controlled trials. The effects of
      therapeutic life review were pooled across the trials. Standardized mean
      differences were calculated for the pooled effects. Heterogeneity was assessed
      using the I2 test. Study quality was assessed using the Cochrane criteria.
      RESULTS: Eight randomized controlled trials met the inclusion criteria. The
      pooled results suggested a desirable effect of therapeutic life review on the
      meaning of life domain of spiritual well-being (standardized mean difference =
      0.33; 95% confidence interval, 0.12 to 0.53), general distress (standardized mean
      difference = -0.32; 95% confidence interval, -0.55 to -0.09), and overall quality
      of life (standardized mean difference = 0.35; 95% confidence interval, 0.15 to
      0.56) when compared to usual care only. Of the three outcomes examined, only the
      pooled effect on overall quality of life remained statistically significant at
      follow-ups up to 3 months after the intervention (standardized mean difference =
      0.82; 95% confidence interval, 0.47 to 1.18). CONCLUSIONS: Therapeutic life
      review is potentially beneficial for people near the end of life. However, the
      results should be interpreted with caution due to the limited number of
      randomized controlled trials and associated methodological weaknesses. Further
      rigorously designed randomized controlled trials are warranted.

PMID- 28488924
TI  - Effects of Caffeine on Countermovement-Jump Performance Variables in Elite Male
      Volleyball Players.
AB  - PURPOSE: To examine the effects of a moderate dose of caffeine in elite male
      volleyball players on countermovement-jump (CMJ) performance, as well as temporal
      concentric- and eccentric-phase effects. METHODS: Ten elite male volleyball
      players took part in 2 experimental days via a randomized crossover trial 1 wk
      apart in which they ingested either 5 mg/kg of caffeine or a placebo in double
      blind fashion. Heart rate and blood pressure were measured at rest and 60 min
      postingestion. Afterward, subjects also performed 3 CMJ trials 60 min
      postingestion, of which the average was used for further analysis. They filled
      out a questionnaire on possible side effects 24 h posttrial. RESULTS: Caffeine
      intake, compared with placebo, increased CMJ peak concentric force (6.5% +/-
      6.4%; P = .01), peak power (16.2% +/- 8.3%; P < .01), flight time (5.3% +/- 3.4%;
      P < .01), velocity at peak power (10.6% +/- 8.0%; P < .01), peak displacement
      (10.8% +/- 6.5%; P < .01), peak velocity (12.6% +/- 7.4%; P < .01), peak
      acceleration (13.5% +/- 8.5%; P < .01), and the force developed at peak power
      (6.0% +/- 4.0%; P < .01) and reduced the time between peak power and peak force
      (16.7% +/- 21.6%, P = .04). Caffeine increased diastolic blood pressure by 13.0%
      +/- 8.9% (P < .05), whereas no adverse side effects were found. CONCLUSIONS: The
      ingestion of 5 mg/kg of anhydrous caffeine improves overall CMJ performance
      without inducing side effects.

PMID- 28488925
TI  - Strategies to address the shortcomings of commonly used advanced chronic heart
      failure descriptors to improve recruitment in palliative care research: A
      parallel mixed-methods feasibility study.
AB  - BACKGROUND: Recruitment challenges contribute to the paucity of palliative care
      research with advanced chronic heart failure patients. AIM: To describe the
      challenges and outline strategies of recruiting advanced chronic heart failure
      patients. DESIGN: A feasibility study using a pre-post uncontrolled design.
      SETTING: Advanced chronic heart failure patients were recruited at two nurse-led
      chronic heart failure disease management clinics in Ireland Results: Of 372
      patients screened, 81 were approached, 38 were recruited (46.9% conversion to
      consent) and 25 completed the intervention. To identify the desired population, a
      modified version of the European Society of Cardiology definition was used
      together with modified New York Heart Association inclusion criteria to address
      inter-study site New York Heart Association classification subjectivity. These
      modifications substantially increased median monthly numbers of eligible patients
      approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9).
      Analysis using a mortality risk calculator demonstrated that recruited patients
      had a median 1-year mortality risk of 22.7 and confirmed that the modified
      eligibility criteria successfully identified the population of interest. A
      statistically significant difference in New York Heart Association classification
      was found in recruited patients between study sites, but no statistically
      significant difference was found in selected clinical parameters between these
      patients. CONCLUSION: Clinically relevant modifications to the European Society
      of Cardiology definition and strategies to address New York Heart Association
      subjectivity may help to improve advanced chronic heart failure patient
      recruitment in clinical settings, thereby helping to address the paucity of
      palliative care research this population.

PMID- 28488926
TI  - Removal of glyphosate and aminomethylphosphonic acid from synthetic water by
      nanofiltration.
AB  - The removal of glyphosate and aminomethylphosphonic acid (AMPA) with synthetic
      water was carried out on a lab-scale nanofiltration unit using two membranes, NFX
      and NFW. The presence of humic acid and some inorganic matters (CaCl2 and NaCl)
      was tested in the experiment. The results demonstrate that NFX exhibits better
      separation performance than NFW. The herbicide filtration is found to have little
      effect on the permeate flux as compared to transmembrane pressure. Intermediate
      concentrations of NaCl act positively on foulant separation, and an increment of
      3.3-5.4 percentage points in foulant rejection is obtained with the addition of
      100 mg/L of NaCl. In Contrast, CaCl2 has negative effect on foulant separation
      during nanofiltration. Humic acid alone shows little influence on the rejection
      performance, whereas it is slightly improved in the coexistence of humic acid and
      CaCl2. The nanofiltration technology proves to be a good approach to treat the
      problem of pesticide micropollution in a one-step process. This work clearly
      shows that the composition of the water matrices may influence the efficiency of
      the nanofiltration process in terms of the separation of the micropollutants.

PMID- 28488927
TI  - Distinct Motivational Effects of Contingent and Noncontingent Rewards.
AB  - When rewards are available, people expend more energy, increasing their
      motivational vigor. In theory, incentives might drive behavior for two distinct
      reasons: First, they increase expected reward; second, they increase the
      difference in subjective value between successful and unsuccessful performance,
      which increases contingency-the degree to which action determines outcome.
      Previous studies of motivational vigor have never compared these directly. Here,
      we indexed motivational vigor by measuring the speed of eye movements toward a
      target after participants heard a cue indicating how outcomes would be
      determined. Eye movements were faster when the cue indicated that monetary
      rewards would be contingent on performance than when the cue indicated that
      rewards would be random. But even when the cue indicated that a reward was
      guaranteed regardless of speed, movement was still faster than when no reward was
      available. Motivation by contingent and certain rewards was uncorrelated across
      individuals, which suggests that there are two separable, independent components
      of motivation. Contingent motivation generated autonomic arousal, and unlike
      noncontingent motivation, was effective with penalties as well as rewards.

PMID- 28488928
TI  - Do subjective assessments of running patterns reflect objective parameters?
AB  - Running patterns are often categorized into subgroups according to common
      features before data analysis and interpretation. The Volodalen(r) method is a
      simple field-based tool used to classify runners into aerial or terrestrial using
      a 5-item subjective rating scale. We aimed to validate the Volodalen(r) method by
      quantifying the relationship between its subjective scores and 3D biomechanical
      measures. Fifty-four runners ran 30 s on a treadmill at 10, 12, 14, 16, and 18 km
      h-1 while their kinematics were assessed subjectively using the Volodalen(r)
      method and objectively using 3D motion capture. For each runner and speed, two
      researchers scored the five Volodalen(r) items on a 1-to-5 scale, which addressed
      vertical oscillation, upper-body motion, pelvis and foot position at ground
      contact, and footstrike pattern. Seven 3D biomechanical parameters reflecting the
      subjective items were also collected and correlated to the subjective scores.
      Twenty-eight runners were classified as aerial and 26 as terrestrial. Runner
      classification did not change with speed, but the relative contribution of the
      biomechanical parameters to the subjective classification was speed dependent.
      The magnitude of correlations between subjective and objective measures ranged
      from trivial to very large. Five of the seven objective parameters significantly
      differed between aerial and terrestrial runners, and these parameters
      demonstrated the strongest correlations to the subjective scores. Our results
      support the validity of the Volodalen(r) method, whereby the visual appreciation
      of running gait reflected quantifiable objective parameters. Two minor
      modifications to the method are proposed to simplify its use and improve
      agreement between subjective and objective measures.

PMID- 28488929
TI  - Mobile Diagnostic Units for Rural Patients in Colombia.
AB  - BACKGROUND: The literature on the use of mobile diagnostic units for the adult
      population is limited. This is a report for the first time in Colombia (Latin
      America) on the use of mobile diagnostic units for patients in rural areas and
      resolution of complex cases through telemedicine. INTRODUCTION: Telemedicine is
      an alternative because it takes advantage of advances in telecommunications and
      technology for the provision of health services to patients in rural areas of a
      country. MATERIALS AND METHODS: A pilot program for mobile patient diagnosis was
      developed in three rural areas of central Colombia. The mobile unit was named
      Mobile dIagnostiC Unit (MICU). The unit includes a medical stretcher, dresser,
      washbasin, computer, videoconference equipment, satellite connectivity, and
      digital medical equipment: electrocardiogram, stethoscope, oximeter, and
      thermometer. RESULTS: The number of patients attended during the 3 days of
      activity was 108, ~36 each day. None of the patients (100%) was familiar with
      digital diagnostic tools and telemedicine. The entire population who attended
      (100%) was satisfied with the care, health education, and diagnosis received.
      DISCUSSION: Our case report shows that the use of MICUs with the support of
      telemedicine offers benefit to the rural population in the geographic zone chosen
      in Colombia. CONCLUSIONS: With greater coverage and access for patients to health
      services via mobile telemedicine units, it is possible to increase the quality of
      care.

PMID- 28488930
TI  - Preparation of liposome bearing disulfide proteinoid and its reduction-responsive
      release property.
AB  - Egg phosphatidylcholine (Egg PC) liposome bearing a disulfide proteinoid
      exhibited a reduction-responsive release property. Proteinoid composed of Asp,
      Leu, and cystamine (Prot(ALC)) and Asp and Leu (Prot(AL)) were synthesized by
      thermal condensation, confirmed by Raman, FT-IR, 1H NMR and 13C NMR spectroscopy.
      Egg PC liposome bearing the proteinoid was prepared by a film hydration and
      sonication method. The fluorescence quenching of dye (i.e. calcein) loaded in
      liposome bearing the proteinoid was 68.1-78.1%. The mean hydrodynamic diameter of
      liposome bearing the proteinoid was less than 200 nm and it decreased with
      increasing amount of the proteinoid. On the TEM photo, multi-lamellar vesicles
      were observed and the vesicle diameter was 100-300 nm. At all the phospholipid to
      proteinod ratios tested (i.e. 1:0.01, 1:0.02, and 1:0.05 (w/w)), the release
      degree in 12 h of dye loaded in liposome bearing Prot(AL) was less than 2%, and
      it was almost the same regardless of dithiothreitol (DTT, a reducing agent)
      concentration (i.e. 0, 10, and 20 mM). Whereas the release degree of dye loaded
      in liposome bearing Prot(ALC) was 1.5-8.4% and it was significantly dependent on
      DTT concentration.

PMID- 28488931
TI  - Lightweight bricks manufactured from ground soil, textile sludge, and coal ash.
AB  - Reuse of textile sludge as construction materials has been proved to an economic
      and environmental friendly strategy to mitigate its disposal problems. Previous
      studies have illustrated the successful fabrication of common fired bricks using
      textile sludge as a partial replacement of clay, but no such a specific work was
      focused on the feasibility of manufacturing lightweight bricks from textile
      sludge. In this study, a strategy involving the mixing of ground soil, textile
      sludge, and coal ash as the raw materials for the successful production of
      lightweight bricks is presented. Coal ash and ground soil have different
      combustible contents but similar main chemical composition, which facilitates the
      separable adjustment of these two factors of the raw material mixture to achieve
      their suitable values at the same time, and thus results in the successful
      manufacture of lightweight bricks. To meet the requirement for compressive
      strength and consume textile sludge as more as possible, an optimal ratio of the
      raw materials was obtained as textile sludge:coal ash:ground soil = 20:20:60. The
      brick products manufactured from this ratio show a compressive strength of 13.7
      MPa, bulk density of 1.47 g cm-3, water absorption of 14.6%, and volumetric
      shrinkage of 13.61% after sintering. The results of toxicity characteristic
      leaching procedure test show that the heavy metal concentrations in the leachates
      of the brick products are very low, which also satisfy the regulations. This
      study provides a feasible and economical technology for the treatment of textile
      sludge.

PMID- 28488932
TI  - Powassan/Deer Tick Virus and Borrelia Burgdorferi Infection in Wisconsin Tick
      Populations.
AB  - Powassan/Deer Tick Virus (POWV/DTV) is an emerging cause of arboviral
      neuroinvasive disease in the upper Midwest. These studies describe the prevalence
      and geographic distribution of Wisconsin ticks carrying POWV/DTV as well as the
      high frequency of Ixodes scapularis ticks coinfected with both POWV/DTV and
      Borrelia burgdorferi, the causative agent of Lyme disease. These findings suggest
      that concurrent transmission of POWV/DTV and B. Burgdorferi from coinfected ticks
      is likely to occur in humans.

PMID- 28488933
TI  - Zebrafish as a Screening Model for Testing the Permeability of Blood-Brain
      Barrier to Small Molecules.
AB  - The objective of this study was to evaluate the permeability of small molecules
      into the brain via the blood-brain barrier in zebrafish and to investigate the
      possibility of using this animal model as a screening tool during the early
      stages of drug discovery. Fifteen compounds were used to understand the
      permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma
      concentration was compared between the two animal models. The partition
      coefficient (Kp,brain), estimated using the concentration ratio at designated
      times (0.167, 0.25, 0.5, or 2 h) after oral administrations (per os, p.o), ranged
      from 0.099 to 5.68 in zebrafish and from 0.080 to 11.8 in mice. A correlation was
      observed between the Kp,brain values obtained from the zebrafish and mice,
      suggesting that zebrafish can be used to estimate Kp,brain to predict drug
      penetration in humans. Furthermore, in vivo transport experiments to understand
      the permeability glycoprotein (P-gp) transporter-mediated behavior of loperamide
      (LPM) in zebrafish were performed. The zebrafish, Kp,brain,30min of LPM was
      determined to be 0.099 +/- 0.069 after dosing with LPM alone, which increased to
      0.180 +/- 0.115 after dosing with LPM and tariquidar (TRQ, an inhibitor of P-gp).
      In mouse, the Kp,brain,30min of LPM was determined to be 0.080 +/- 0.004 after
      dosing with LPM alone and 0.237 +/- 0.013 after dosing with LPM and TRQ. These
      findings indicate that the zebrafish could be used as an effective screening tool
      during the discovery stages of new drugs to estimate their distribution in the
      brain.

PMID- 28488935
TI  - Seroprevalence and Factors Associated with Toxoplasma gondii Infections in Sheep
      in Latvia: Latvian Dark Headed Sheep Breed Associated with Higher Seroprevalence.
AB  - Toxoplasma gondii is a protozoan parasite with both public health and veterinary
      importance. The aims of our study were to estimate the T. gondii seroprevalence
      in sheep in Latvia and to evaluate potential risk factors for seropositivity. The
      blood samples investigated were collected from 1039 sheep from 84 farms between
      January 2012 and April 2013. The sera were tested for immunoglobulin G antibodies
      against T. gondii using an in-house enzyme-linked immunosorbent assay. Antibodies
      against T. gondii were detected in 179 (17.2%) of the sheep, and at least one
      seropositive sheep was found on 37 (44.0%) of the farms. The seroprevalence was
      significantly higher in adult (over 1 year old) sheep than in juveniles-the adult
      sheep had 1.8 times higher odds to test seropositive than did the juveniles. The
      seroprevalence was significantly higher in Latvian Dark Headed sheep than in
      crossbreed and German Merino sheep. Sheep from large herds (with more than 100
      sheep), as well as those from farms with cattle, had higher odds to test
      seropositive, whereas the presence of poultry on the farm appeared as a
      protecting factor. The results show that sheep in Latvia are commonly exposed to
      T. gondii.

PMID- 28488934
TI  - The Zebrafish curly fry Is Required for Proper Centrosome and Mitotic Spindle
      Assembly.
AB  - The zebrafish curly fry (cfy) mutation leads to a dramatic increase in mitotic
      index and cell death starting during neural tube formation. The mutant phenotype
      is cell autonomous and does not result from defects in apical/basal polarity
      within the neuroepithelium. The increase in mitotic index could be due to
      increased proliferation or cell cycle arrest in mitosis. cfy embryos were
      analyzed to examine these two possibilities. By labeling embryos with a pulse of
      BrdU and anti-phospho-histone 3 and examining the DNA content by fluorescence
      activated cell sorting, we show that cfy mutants exhibit no increase in
      proliferation, but a significant increase in the number of cells arrested in
      mitosis. Furthermore, time-lapse microscopy in vivo confirmed that a great
      majority of dividing cells arrest during mitosis and that these mitotically
      arrested cells die in cfy embryos. Finally, immunostaining and confocal
      microscopy in cfy mutant embryos revealed that mitotic cells in mutants contain
      aberrant centrosomes and often exhibit monopolar spindles, thereby leading to
      mitotic cell cycle arrest. Our results suggest that the cfy gene is required for
      proper centrosome assembly and mitotic spindle formation, therefore critical for
      normal cell division.

PMID- 28488936
TI  - Long-Term Social Recognition Memory in Zebrafish.
AB  - In species in which individuals live in stable social groups, individual
      recognition is expected to evolve to allow individuals to remember past
      interactions with different individuals and adjust future behavior toward them
      accordingly. Thus, social memory is expected to be a ubiquitous component of
      social cognition of social species. However, few studies have investigated the
      occurrence of social memory in non-mammals. Here we evaluated the ability of
      zebrafish (Danio rerio) to recognize different conspecifics and to retain this
      information in long lasting (i.e. 24 h) memories. We used a social discrimination
      paradigm, adapted from mouse studies, in which the focal individual meets two
      pairs of conspecifics in two consecutive days: one conspecific is the same in
      both days and the other is different between days 1 and 2. If animals have the
      ability to discriminate between different conspecifics, it is predicted that they
      will spend more time exploring the novel than the familiar (i.e. already seen in
      day 1) conspecific. In this study, zebrafish with access to both olfactory and
      visual conspecific cues exhibited consistent recognition of a previously
      encountered (familiar) conspecific after a 24 h delay. This result supports the
      hypothesis that long-term social memory, previously described in mammals, is also
      present in zebrafish, hence extending the evidence for the presence of this type
      of memory to teleost fish.

PMID- 28488937
TI  - Traditional balance and slackline training are associated with task-specific
      adaptations as assessed with sensorimotor tests.
AB  - The purpose of this study was to measure alterations in sensorimotor skills and
      balance resulting from slackline training and conventional balance training.
      Forty-three physically fit subjects were randomized into three groups. Two groups
      practiced three times a week for 15 minutes, including at least once supervised
      session, on the slackline or perform conventional balance training for 6 weeks.
      The control group was not allowed to perform any balance training. Before and
      after the intervention, the subjects underwent sensorimotor and strength tests.
      The results of our intra-class correlation analysis showed that the stability
      parameters from the multifunctional training device (MFT, 0.7), the height during
      the countermovement jump (CMJ, 0.95) and the maximum force (0.88) during leg
      press showed excellent reliability. A post hoc comparison indicated a larger
      effect of conventional training (almost 11% reduction in MFT stability) compared
      with slackline training in group-wide comparisons of the pre- to the post
      training measurements. The factor analysis showed that stability and sensorimotor
      assessment using MFT were correlated, as were height during CMJ and maximal force
      during leg press, which represented dynamic strength. Because CMJ had the highest
      intra-class correlation value, it was chosen over maximum force from leg press.
      For these reasons, only two out of nine measured parameters, namely MFT stability
      and CMJ, were analysed across groups. The only observed difference between the
      two groups was MFT stability (slackline - 1.5%, conventional - 13%), whereas the
      improvement of CMJ was the same (slackline + 3%, conventional + 3%). It can be
      concluded that slacklining is partly complementary to conventional sensorimotor
      training.

PMID- 28488938
TI  - Aerobic sludge granulation for simultaneous anaerobic decolorization and aerobic
      aromatic amines mineralization for azo dye wastewater treatment.
AB  - In this study, the capability of using aerobic granules to undergo simultaneous
      anaerobic decolorization and aerobic aromatic amines degradation was demonstrated
      for azo dye wastewater treatment. An integrated acclimation-granulation process
      was devised, with Mordant Orange 1 as the model pollutant. Performance tests were
      carried out in a batch column reactor to evaluate the effect of various operating
      parameters. The optimal condition was to use 1.0-1.7 mm (1.51 +/- 0.33 mm)
      granules, 5 g/L biomass, and 4000 mg/L organics as nutrient; and supplement the
      wastewater with 1  mg/L dissolved oxygen. This led to a dye mineralization of 61
      +/- 2%, an anaerobic dye removal of 88 +/- 1%, and an aerobic aromatic amines
      removal of 70 +/- 3% within 48 h. This study showed that simultaneous
      anaerobic/aerobic process by aerobic granules could be a possible alternative to
      the conventional activated sludge process.

PMID- 28488940
TI  - Marathon Specialization in Elites: A Head Start for Africans.
AB  - PURPOSE: To assess differences in event-specific specialization between elite
      African and non-African male marathon runners based on age, performance, and
      career length. METHODS: The top 90 African marathoners from 2001 to 2015 were
      compared with the top 90 non-African marathoners from the same time period across
      various markers related to specialization age, performance, and career length.
      Independent t tests were used to identify significant differences (P < .05)
      between the African and non-African groups. Linear regression was used to explore
      the relationship between first half-marathon and best full-marathon performance.
      A 1-way ANOVA and Bonferroni correction was used to assess differences in
      specialization age and rates of performance improvement and decline. RESULTS:
      African marathoners were found to specialize, reach peak levels of performance,
      and retire at younger ages than non-African marathoners (P < .001). In addition,
      African marathoners were found to be faster at these same career time points and
      in half-marathon performance (P < .001). There was no significant difference in
      the number of career marathons run between groups, but African marathoners were
      found to race more frequently than non-African marathoners (P < .001). Half
      marathon performance was positively correlated with marathon performance (r2 =
      .67). Marathon athletes who specialized at early ages experienced significantly
      higher rates of improvement than those who specialized at older ages. (P < .05).
      CONCLUSIONS: The findings suggest that elite African marathoners achieve a
      greater level of performance at younger ages than their non-African counterparts.
      Furthermore, current marathon talent-identification practice may benefit from
      using half-marathon performance.

PMID- 28488939
TI  - Differences in morning-evening type and sleep duration between Black and White
      adults: Results from a propensity-matched UK Biobank sample.
AB  - Biological evidence suggests that ethno-racial differences in morning-evening
      type are possible, whereby Blacks may be more likely to be morning type compared
      to Whites. However, population-level evidence of ethno-racial difference in
      morning-evening type is limited. In an earlier study, we reported that morning
      type was more prevalent in Blacks compared to Whites in the United Kingdom (UK)
      Biobank cohort (N = 439 933). This study aimed to determine if these ethno-racial
      differences persisted after accounting for an even broader range of social,
      environmental and individual characteristics and employing an analytic approach
      that simulates randomization in observational data, propensity score modeling.
      Data from UK Biobank participants whose self-identified race/ethnicity was
      Black/Black British or White; who did not report daytime napping, shift work or
      night shift work; who provided full mental health information; and who were
      identified using propensity score matching were used (N = 2044). Each sample was
      strongly matched across all social, environmental and individual characteristics
      as indicated by absolute standardized mean differences <0.09 for all variables.
      The prevalence of reporting nocturnal short, adequate and long sleep as well as
      morning, intermediate and evening type among Blacks (n = 1022) was compared with
      a matched sample of Whites (n = 1022) using multinomial logistic regression
      models. Blacks had a 62% greater odds of being morning type [odds ratio (OR) =
      1.620, 95% confidence interval (CI): 1.336-1.964, p < .0001] and a more than
      threefold greater odds of reporting nocturnal short sleep (OR = 3.453, 95% CI:
      2.846-4.190, p < .0001) than Whites. These data indicate that the greater
      prevalence of morning type and short nocturnal sleep in Blacks compared to Whites
      is not fully explained by a wide range of social and environmental factors. If
      sleep is an upstream determinant of health, these data suggest that ethno
      racially targeted public health sleep intervention strategies are needed.

PMID- 28488941
TI  - A-V block as presentation of cardiac amyloid: prominent infiltration of
      conduction tissue revealed by endomyocardial biopsy.

PMID- 28488942
TI  - Goat Model for Direct Visualizing the Effectiveness of Detaching Sinus Mucosa in
      Real Time During Crestal Maxillary Sinus Floor Elevation.
AB  - The procedure of crestal maxillary sinus floor elevation presents a great
      challenge to the field of implant dentistry. Due to the limited visualization in
      this procedure, the effectiveness of detaching sinus mucosa could not be assessed
      in real time. We recently developed an ex vivo goat sinus model by cutting the
      goat residual skulls along four lines determined from computerized tomography
      (CT) scans, extracting the maxillary premolar or molar teeth, and preparing
      implant socket in the maxilla. The generated ex vivo goat sinus models exposed
      the maxilla and the whole maxillary sinus mucosa, thus enabling real-time
      observation of detaching maxillary sinus mucosa via directly visualizing the
      working situation of sinus lift tool in the models and directly measuring the
      length of detached mucosa and space volume generated under the elevated sinus
      mucosa. One commercially available umbrella-shaped sinus lift curette was used to
      detach the maxillary sinus mucosa to evaluate the effectiveness of the ex vivo
      goat sinus models. The results showed that this curette could detach the sinus
      mucosa 3.75 mm in length in the mesiodistal direction and 2.81 mm in the buccal
      palatal direction. Moreover, a space volume of 52.7 MUl could be created under
      the elevated sinus mucosa in the goat ex vivo models. All the experimental
      results suggested that this ex vivo goat sinus model might be useful in the
      evaluation of improved or newly designed sinus lift tools for elevating the
      maxillary sinus mucosa via the crestal approach.

PMID- 28488943
TI  - Effect of blue-blocking glasses in major depressive disorder with sleep onset
      insomnia: A randomized, double-blind, placebo-controlled study.
AB  - Blue wavelengths form the portion of the visible electromagnetic spectrum that
      most potently regulates circadian rhythm. We hypothesized that wearing blue
      blocking (BB) glasses in the evening may influence circadian rhythm disturbances
      in patients with major depressive disorder (MDD), resulting in improved sleep and
      mood. We used a randomized placebo-controlled double-blinded design. Patients
      with MDD with sleep onset insomnia were randomly assigned to wearing either BB
      glasses or clear glasses (placebo). Patients were instructed to wear the glasses
      from 20:00 hours until bedtime for 2 weeks. We assessed sleep state (sleep
      quality on a visual analog scale, the Morningness-Eveningness Questionnaire
      [MEQ], and a sleep diary) and depressive symptoms at baseline and after 2 weeks.
      Data were analyzed with a full analysis set. In total, 20 patients were randomly
      assigned to the BB and placebo groups (BB group, n = 10; placebo group, n = 10).
      There were three dropouts (BB group, n = 1; placebo group, n = 2). At baseline,
      sleep quality, sleep latency (assessed via a sleep diary), and antipsychotics use
      differed between the groups. To take account of these differences, the baseline
      sleep state or depressive symptoms and antipsychotics use were used as covariates
      in the later analysis. The change scores for sleep quality did not show a
      significant improvement in the BB group compared with the placebo group (mean
      [standard deviation, SD] scores for BB versus placebo: 36.1 [31.7] versus 16.2
      [15.1], p = 0.43), although half of the BB group showed a clear improvement in
      sleep quality. The change in MEQ scores did not significantly differ between the
      groups (p = 0.14), although there was a trend of a shift to morning type in the
      BB group (3.10 [4.95] points) and to evening type in the placebo group (0.50
      [3.89] points). There were no statistically significant changes in depressive
      symptoms in either group. Across both groups, 40% of the participants reported
      pain or discomfort from wearing the glasses, which were available in only one
      size. Thus, the failure to find significant differences may have resulted from
      the glasses used in this study. Glasses fitted to individual patients may improve
      efficacy and safety. Replication of the study with a larger sample size and size
      adjustable glasses is needed.

PMID- 28488944
TI  - A Scalable and Accurate Method for Quantifying Vector Genomes of Recombinant
      Adeno-Associated Viruses in Crude Lysate.
AB  - Increasing interest and application of recombinant adeno-associated viruses
      (rAAVs) in basic and clinical research have urged efforts to improve rAAV
      production quality and yield. Standard vector production workflows call for
      genome titration of purified vectors at the endpoint of production to assess
      yield. Unfortunately, quality control measures for preparations during mid
      production steps and economical means to assess the fidelity of multiple batches
      of rAAV preparations are lacking. Here we describe a scalable and accurate method
      for the direct quantitative polymerase chain reaction (qPCR) titration of rAAV
      genomes in crude lysate. Lysate samples are pretreated with DNase I to remove
      vector and packaging plasmid DNAs, followed by proteinase K to release
      endonuclease-resistant packaged viral genomes and to proteolyze factors inherent
      to crude lysates that can impinge upon quantitative PCR efficiencies. We show
      that this method is precise, scalable, and applicable for vector genome
      titrations of both single-stranded and self-complementary AAV genomes
      irrespective of serotype differences-a major limitation for standard lysate
      transduction methods that indirectly screen for vector packaging efficiency. Our
      described method therefore represents a significant improvement to rAAV vector
      production in terms of alleviating time and cost burdens, in-process quality
      control assessment, batch/lot monitoring in large-scale preparations, and good
      manufacturing practices.

PMID- 28488945
TI  - Tropical pulmonary eosinophilia masquerading as asthma in a 5-year-old girl.
AB  - Tropical pulmonary eosinophilia (TPE) is an exaggerated immunological response to
      filarial antigens mainly seen in adults in endemic areas and is uncommonly
      reported in children. The diagnosis is frequently delayed as it mimics asthma
      clinically, while the chest radiograph might show miliary mottling which is often
      confused with that in pulmonary tuberculosis. A 5-year-old girl presented with
      episodes of nocturnal cough, wheeze, low grade fever and breathlessness for the
      previous 4 months and was being treated for asthma. The absolute eosinophil count
      was markedly raised (53 * 109/L) with prominent bilateral infiltrates on the
      chest radiograph. Serology for microfilaria and a test for microfilaria antigens
      were positive and the patient showed a dramatic response to diethylcarbamazine,
      which confirmed the diagnosis of TPE. TPE is an important differential diagnosis
      of asthma especially in endemic areas.

PMID- 28488946
TI  - Laparoscopic Reconstruction in Post-Tubercular Urinary Tract Strictures:
      Technical Challenges.
AB  - BACKGROUND: Genitourinary tuberculosis still continues to plague developing
      countries and is a significant cause of morbidity as well as mortality in the
      developing world. At present, nearly 55% of the patients of genitourinary
      tuberculosis (GUTB) need surgical management. Owing to the presence of dense
      adhesions and loss of normal anatomical planes, GUTB was considered to be a
      contraindication to laparoscopic surgery. However, recent literature shows
      laparoscopy to be feasible in GUTB. Our study aimed at identifying the challenges
      in laparoscopic urinary tract reconstructive surgery in genitourinary
      tuberculosis-related urinary tract obstruction. MATERIALS AND METHODS: The
      details of 6 patients who underwent different types of laparoscopic
      reconstructive surgery for genitourinary tuberculosis-related urinary tract
      obstruction from January 2014 to December 2015 were reviewed. Baseline
      characteristics, indications of surgery, type of surgery, operative duration,
      blood loss, and follow-up details were noted. All patients received
      antitubercular treatment before surgery as per the direct observed treatment
      short-course regimen followed in our country. RESULTS: We performed one bilateral
      laparoscopic pyeloplasty, one unilateral laparoscopic pyeloplasty, two
      laparoscopic ureteroneocystostomies, and two ureteroureterostomies. Difficulty
      was encountered during dissection owing to the presence of adhesions, but
      conversion to open surgery was not done in five cases. Dense adhesions adjacent
      to the common iliac vessels necessitated conversion to open surgery in one of the
      ureteroureterostomies. Stenting was done in all the patients. All patients had
      uneventful postoperative recovery. Functional imaging following stent removal
      showed unobstructed tracer flow, showing successful operative outcome.
      CONCLUSIONS: Our study showed that laparoscopic reconstructive surgery is
      feasible in genitourinary tuberculosis despite the presence of adhesions that may
      pose a challenge to dissection. This is in contrast to the previous studies which
      conclude that genitourinary tuberculosis is a relative contraindication to
      laparoscopic surgery.

PMID- 28488947
TI  - Translation control: Learning from viruses, again.
AB  - Viruses are powerful tools to uncover cellular processes. Through viral studies
      we have recently identified a novel translational control mechanism that involves
      the DEAD-box helicase Dhh1/DDX6 and RNA folding within coding sequences (CDSs).
      All Dhh1-dependent mRNAs, viral and cellular ones, (i) contain long and highly
      structured CDSs, (ii) are directly bound by Dhh1 with a specific pattern, (iii)
      are activated at the translation initiation step and (iv) express proteins
      associated with the endoplasmic reticulum. The obtained results uncover a novel
      layer of translation regulation associated with translation at the endoplasmic
      reticulum conserved from yeast to humans and hijacked by viruses.

PMID- 28488948
TI  - The effectiveness of augmented versus standard individual placement and support
      programs in terms of employment: a systematic literature review.
AB  - BACKGROUND: The Individual Placement and Support (IPS) program is a well-studied
      vocational rehabilitation program. Although it is more effective than usual care,
      it is not effective for everyone. This offers an opportunity for program
      improvement. AIMS: This systematic literature review examines the state of
      knowledge regarding the effectiveness of augmented versus standard IPS for people
      with severe mental illness (SMI). We address the questions, "What IPS
      augmentations have been tested?" and "What is the evidence for the effectiveness
      of augmented IPS versus standard IPS in terms of employment?" METHODS: This
      systematic literature review used publically available peer-reviewed studies
      published between January 2002 and January 2016 in either: (1) Medline Current,
      (2) Medline In-process, (3) PsycINFO, (4) Econlit or (5) Web of Science. RESULTS:
      5718 unique citations were identified; seven articles from five studies were
      included. Of these studies, four were rated as having moderate risk of bias and
      one as having high risk. CONCLUSIONS: The results suggest that augmentations of
      IPS focusing on cognitive and psychosocial skills training, may have additional
      effects to standard IPS. Areas in need of further research related to the process
      and targeting of those interventions are discussed.

PMID- 28488949
TI  - Decrease Hospital Spending: There's an App for That! A Retrospective Analysis of
      Implementation of a Mobile Resident Handbook on Hospital Costs and Disposition.
AB  - BACKGROUND: Patient care involves time sensitive decisions. Matching a patient's
      presenting condition with possible diagnoses requires proper assessment and
      diagnostic tests. Timely access to necessary information leads to improved
      patient care, better outcomes, and decreased costs. INTRODUCTION: This study
      evaluated objective outcomes of the implementation of a novel Resident Handbook
      Application (RHAP) for smart phones. METHODS: The RHAP included tools necessary
      to make proper assessments and to order appropriate tests. The RHAPs
      effectiveness was accessed using the Military Health System Military Mart
      database. This database includes patient specific aggregate data, including
      diagnosis, patient demographics, itemized cost, hospital days, and disposition
      status. Multivariable analysis was used to compare before and after RHAP
      implementation, controlling for patient demographics and diagnosis. Internal
      medicine admission data were used as a control group. RESULTS: There was a
      statistically significant decrease in laboratory costs and a strong trend toward
      statistically significant decreases in the cost of radiology performed after
      implementation of RHAP (p value of <0.02 and <0.07, respectively). There was also
      a decrease in hospital days (3.66-3.30 days), in total cost per admission
      ($18,866-$16,305), and in cost per hospital day per patient ($5,140-$4,936).
      During the same time period a Control group had no change or increases in these
      areas. CONCLUSIONS: The use of the RHAP resulted in decreases in costs in a
      variety of areas and a decrease in hospital bed days without any apparent
      negative effect upon patient outcomes or disposition status.

PMID- 28488950
TI  - Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients.
AB  - BACKGROUND: Ross syndrome is diagnosed by the presence of segmental anhidrosis,
      areflexia, and tonic pupils. Fewer than 60 cases have been described in
      literature so far. There have been reports of presence of antibodies in such
      patients, suggesting an autoimmune pathogenesis. METHODS: We describe the
      clinical profile in this case series of 11 patients with Ross syndrome and
      discuss the current status of autoimmunity in its pathogenesis and the
      management. RESULTS: Of the 11 patients with Ross syndrome there was an almost
      equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset
      of symptoms was 26 years. Patients took an average of 6 years to present to a
      tertiary center. Sixty-three percent of the patients presented with complaints of
      excessive sweating, whereas only 27% had complaints of decreased sweating over a
      particular area of the body. Only 45% of the patients had the complete triad of
      Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent
      reflexes. Eighty-nine percent of the patients had documented absent sympathetic
      skin response on electromyography. The various markers of autoimmunity were
      negative in all patients who were investigated for the same in this series.
      Ninety percent of the patients were managed conservatively. CONCLUSIONS: These
      findings suggest that, in Ross syndrome, generalized injury to ganglion cells or
      their projections are not purely autoimmune-mediated.

PMID- 28488951
TI  - Treatment Outcomes in 1p19q Co-deleted/Partially Deleted Gliomas.
AB  - BACKGROUND: Radiotherapy with procarbazine, lomustine, and vincristine improves
      overall survival (OS) in patients with 1p19q co-deleted anaplastic
      oligodendroglioma/anaplastic oligoastrocytoma. METHODS: This retrospective
      analysis investigated outcomes in patients with 1p19q co-deleted/partially
      deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or
      anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed
      using the Kaplan-Meier method and prognostic factors using the Cox proportional
      hazard model. RESULTS: A total of 106 patients (between December 1997 and
      December 2013) were included. Median age was 40 years (19-66), 58 were male
      (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients
      (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27
      (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients,
      respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85
      patients with sufficient material. Upfront treatment was given in 72 (68%)
      patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47
      patients (44%) was 34.7 months and 41.2 months in 9 patients with co
      deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic
      oligoastrocytoma who received upfront temozolomide alone. Median OS was not
      reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On
      multivariable analysis for all patients, receipt of therapy upfront versus none
      (p=0.04), PS 1 versus 0 (p<0.001) and 1p19q co-deletion/incomplete deletion
      versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate
      dehydrogenase-1 status was not prognostic for PFS. CONCLUSIONS: With similar
      survival patterns in low-grade/anaplastic gliomas, molecular characteristics may
      be more important than histological grade. Longer follow-up and results of
      prospective trials are needed for definitive guidance on treatment of these
      patients.

PMID- 28488952
TI  - Aneurysm Tears Caused by an Aneurysm Clip Springing from the Clip Applier.
AB  - We experienced two cases in which aneurysm clips sprang from the applier. In case
      1, a subdural haematoma from a ruptured anterior cerebral artery aneurysm was
      detected. When the clip was opened for final positioning, it suddenly sprang from
      the applier and ruptured the aneurysm. In case 2, the clip suddenly sprang from
      the applier as the surgeon opened the applier to clip an unruptured anterior
      cerebral aneurysm. These accidental phenomena are rare but dangerous. We present
      these cases to help prevent similar occurrences in the future. Video recordings
      of actual procedures can point to potential mechanisms and help reduce the
      incidence of this complication.

PMID- 28488953
TI  - Atypical Meningioma: Referral Patterns, Treatment and Adherence to Guidelines.
AB  - OBJECTIVE: To determine the referral rate to radiation oncologist (RO), use of
      postoperative radiotherapy (PORT) and the impact of a clinical practice guideline
      (CPG) on patients with atypical meningioma (AM). METHODS: A retrospective review
      of meningioma patients (n=526) treated between 2003 and 2013 was undertaken.
      Patients' characteristics, extent of surgical resection (EOR), RO referral, PORT,
      date and treatment of first recurrence were collected for all patients >18 years
      with a new diagnosis of AM after surgical resection (n=83). Progression free
      survival (PFS) and overall survival (OS) according to EOR were assessed by the
      Log-Rank test of Kaplan-Meier survival. RESULTS: Median age was 57 years. EOR was
      gross total (GTR) in 44 patients, subtotal (STR) in 36 patients and 3 patients
      had unknown EOR. RO referral rate was 26.5% (n=22); 5 patients initially had GTR
      and 17 had STR. Only 7 patients received PORT. At a median follow up time of 29
      months, recurrences occurred in 28 patients, 4 had GTR, 21 had STR and 3 had an
      unknown EOR. With PORT, 2 patients developed recurrence. 5-year PFS was 62% after
      GTR and 33% after STR (P=0.002). 5-year OS was 92% after GTR and 83% after STR
      (P=0.45). CONCLUSION: In this cohort with AM, RO referral rate was low and was
      not influenced by the CPG. Use of PORT was also low. Given the lack of conclusive
      evidence supporting PORT in such patients, a multidisciplinary approach,
      including RO consultation, is needed to provide patients with optimal and
      individualised care.

PMID- 28488954
TI  - Isolation of a novel orthobunyavirus from bat flies (Eucampsipoda africana).
AB  - The Bunyaviridae family comprises viruses causing diseases of public and
      veterinary health importance, including viral haemorrhagic and arboviral fevers.
      We report the isolation, identification and genome characterization of a novel
      orthobunyavirus, named Wolkberg virus (WBV), from wingless bat fly ectoparasites
      (Eucampsipoda africana) of Egyptian fruit bats (Rousettus aegyptiacus) in South
      Africa. Complete genome sequence data of WBV suggests it is most closely related
      to two bat viruses (Mojui dos Campos and Kaeng Khoi viruses) and an arbovirus
      (Nyando virus) previously shown to infect humans. WBV replicates to high titres
      in VeroE6 and C6-36 cells, characteristic of mosquito-borne arboviruses. These
      findings expand our knowledge of the diversity of orthobunyaviruses and their
      insect vector host range.

PMID- 28488955
TI  - Reporting transfusion-related acute lung injury by clinical and preclinical
      disciplines.
AB  - BACKGROUND: Disciplines involved in diagnosing transfusion-related acute lung
      injury (TRALI) report according to a "one-hit" theory. However, studies showed
      that patients with an underlying condition are at increased risk of the
      development of TRALI. We investigated whether accumulating evidence on the "two
      hit" theory has changed the practice of reporting TRALI. MATERIALS AND METHODS:
      Departments of haematology, haemovigilance, transfusion medicine, intensive care
      and anaesthesiology from all Dutch hospitals with at least five beds equipped for
      mechanical ventilation were invited to participate in an online survey. Using
      clinical vignettes with conjoint analysis we investigated the effect of patients'
      age, admission diagnosis, type and number of transfusions and presence of risk
      factors for acute lung injury on TRALI reporting. A positive beta-coefficient
      indicated a higher likelihood of reporting TRALI. RESULTS: We received 129
      questionnaires (response rate 74%). Respondents were more likely to report TRALI
      in younger patients, if symptoms developed within 2 hours of transfusion and if
      patients had received multiple transfusions. Sepsis and the presence of a risk
      factor for acute lung injury reduced the inclination to report. Transfusion
      medicine physicians and haemovigilance staff no longer took the age of
      transfusion products into account in their diagnostic considerations on TRALI.
      DISCUSSION: We conclude that the multidisciplinary team involved in TRALI
      reporting, still considers TRALI a "one-hit" event, despite accumulating evidence
      that supports the "two-hit" theory. These results suggest that the patients most
      at risk of developing TRALI are not reported to the blood bank.

PMID- 28488956
TI  - Introduction of thromboelastometry-guided administration of fresh-frozen plasma
      is associated with decreased allogeneic blood transfusions and post-operative
      blood loss in cardiopulmonary-bypass surgery.
AB  - BACKGROUND: Cardiac surgery is frequently associated with excessive blood loss
      requiring multiple blood transfusions which are, in turn, associated with
      increased morbidity and mortality. We evaluated the effectiveness of rotational
      thromboelastometry (ROTEM(r))-guided administration of fresh-frozen plasma (FFP)
      with regards to blood loss, transfusion requirements, and major post-operative
      complications. MATERIALS AND METHODS: Coagulation management in 68 prospective
      patients undergoing cardiac surgery with cardiopulmonary bypass was based on a
      treatment algorithm guided by ROTEM(r) measurements. The primary end-point was
      blood loss at 24 hours after surgery. Secondary end-points were: (i) need for
      allogeneic blood products after cardiopulmonary bypass and 24 hours post
      operatively, and (ii) post-operative complications until discharge. The results
      were compared with those of a retrospective, control group of 69 patients who
      received empirical coagulation management before implementation of the ROTEM(r)
      guided algorithm. RESULTS: Although patients with significantly lower haemoglobin
      levels received less packed red blood cells (PRBC) (840 vs 1,120 mL; p=0.031) and
      FFP (480 vs 720 mL; p=0.007) after introduction of the ROTEM(r) algorithm, the
      intra-operative blood loss and post-operative haemoglobin levels were similar in
      the ROTEM(r) and the retrospective control groups. In addition to significantly
      reduced blood loss and decreased requirements for PRBC (30.8 vs 62.3%; p<0.001)
      and FFP (25.0 vs 56.5%; p<0.001), the amounts of PRBC (315 vs 840 mL; p<0.001)
      and FFP (480 vs 840 mL; p=0.001) received during the first 24 hours after surgery
      were significantly reduced in the ROTEM(r) group, as was the duration of post
      operative hospitalisation. DISCUSSION: Compared with empirical treatment, timely
      ROTEM(r)-guided FFP administration during cardiac surgery can reduce not only
      overall blood product use and blood loss but also the duration of
      hospitalisation.

PMID- 28488957
TI  - Cumulative erythrocyte damage in blood storage and relevance to massive
      transfusions: selective insights into serial morphological and biochemical
      findings.
AB  - Elucidating the precise mechanisms of cumulative red cell damages during storage
      and the potential harmful consequences after transfusion are achievable by
      exacting laboratory science and well-defined clinical studies in progress.
      Accordingly, for larger magnitude blood transfusions (i.e. 8-12 U in 24 hours),
      the quality of the stored blood and its characterisation are of special academic
      and clinical importance. Our main objectives in this review are to illuminate
      facets of the red cell storage lesion for prolonged storage (0-42 days) by
      concentrating on various hallmarks of the disorder: 1) identifying and
      characterising serial markers of the progressive lesion with respect to red cell
      dysmorphology, deformability, haemolytic fragility and dysfunction both in
      storage and the microcirculation; and 2) relevant biochemical findings of redox
      status correlated to oxidative stress of erythrocyte proteins. This is
      accomplished in part by reliance on advanced metabolomic and proteomic
      technologies using various sophisticated tools such as high pressure liquid
      chromatography in combination with mass spectrometry of proteins and small
      molecule metabolites. It is anticipated that these sophisticated methodologies
      and the experimental results therein shall lead to further advances in the
      quality improvement of red cell storage.

PMID- 28488958
TI  - Strategies to identify candidates for D variant genotyping.
AB  - BACKGROUND: RhD variants have altered D epitopes and/or decreased antigen copies
      per red cell. Individuals carrying these variants may test antigen negative,
      weakly positive, or positive by serology, and may or may not be at risk of
      alloimmunisation after exposure. There have been recommendations to perform RHD
      genotyping of patients, pregnant women and females of childbearing potential with
      serological weak D phenotype, to guide prophylactic use of Rh immune globulin
      (RhIG), and better conserve D-negative blood products. The purpose of this study
      was to evaluate the performance of a set of empirical criteria to identify such
      patients. MATERIALS AND METHODS: A two-method strategy of gel testing (GT) and
      tube testing (TT) was used for Rh typing of patients with no historical blood
      type in the present institution. A monoclonal-polyclonal blend anti-D was used
      for Rh typing by TT at immediate spin. Three empirical criteria were used to
      identify candidates for genotyping: C1: discrepancy between the two test methods
      and a GT reaction strength >2+ stronger than TT; C2: weak serological reaction,
      defined as reaction strength <=2+ regardless of testing method if both GT and TT
      were performed or reaction strength <=2+ if only GT was performed, or reaction
      strength <=1+ if only TT was performed; C3: presence of anti-D in D-positive
      patients with no history of RhIG use in the preceding 3 months and in whom
      alloanti-D is suspected. RESULTS: Overall, 50 patients, ranging from newly born
      to 93 years old, were identified. Genomic testing confirmed D variants in 49/50
      cases with a positive predictive value of 98%. DISCUSSION: This two-method
      strategy is a powerful screening tool for identifying candidates for RHD
      genotyping. This strategy meets the current requirements of two blood type
      determinations/two specimens in pre-transfusion testing while simultaneously
      identifying candidates for RHD genotyping with a minimal increase in work load
      and cost.

PMID- 28488959
TI  - Temperature-dependent haemolytic propensity of CPDA-1 stored red blood cells vs
      whole blood - Red cell fragility as donor signature on blood units.
AB  - BACKGROUND: To preserve cellular integrity and avoid bacterial growth, storage
      and transfer of blood and blood products follow strict guidelines in terms of
      temperature control. We evaluated the impact of ineligible warming of whole blood
      donations on the quality of blood components. MATERIALS AND METHODS: One-hundred
      and twenty units of whole blood (WB) from eligible blood donors were collected in
      CPDA-1 and stored at 4+/-2  degrees C. During shipment to the blood processing
      centre, a gradual warming up to 17  degrees C was recorded within a period of
      less than eight hours. The warmed units were processed to packed red blood cells
      (PRBCs) or stored as WB units at 4+/-2  degrees C. In-bag haemolysis, osmotic
      fragility (mean corpuscular fragility, MCF) and bacterial growth were assessed in
      blood and blood components throughout the storage period. RESULTS: Normal basal
      and early storage levels of haemolysis were recorded in both PRBC and WB units.
      Thereafter, PRBCs exhibited higher average in-bag haemolysis and MCF index
      compared to the WB units throughout the storage. Moreover, 14.3 and 52.4% of the
      PRBC units exceeded the upper permissible limit of 0.8% haemolysis at the middle
      (1.220+/-0.269%) or late (1.754+/-0.866%) storage period, respectively. MCF index
      was similar in all PRBCs at the middle of storage but significantly lower in the
      non-haemolysed compared to the haemolysed units of PRBCs on the last days. The
      fragility of stored RBCs was proportional to the donor-related values of day 2
      samples (r=0.861, p<10-32). In the qualified PRBCs, MCF was correlated with
      haemolysis at every time point of the storage period (r=0.332, p<0.050).
      Bacterial growth was detected by blood culture in two units of PRBCs. DISCUSSION:
      Transient, gradient warming of whole blood from 4 to 17  degrees C led to
      increased incidence of in-bag haemolysis in PRBC but not in WB units. Haemolysis
      is a multi-parametric phenotype of stored blood, and MCF is a donor-related and
      highly dynamic measure that can, in part, predict the storage lesion.

PMID- 28488960
TI  - Towards pathogen inactivation of red blood cells and whole blood targeting viral
      DNA/RNA: design, technologies, and future prospects for developing countries.
AB  - Over 110 million units of blood are collected yearly. The need for blood products
      is greater in developing countries, but so is the risk of contracting a
      transfusion-transmitted infection. Without efficient donor screening/viral
      testing and validated pathogen inactivation technology, the risk of transfusion
      transmitted infections correlates with the infection rate of the donor
      population. The World Health Organization has published guidelines on good
      manufacturing practices in an effort to ensure a strong global standard of
      transfusion and blood product safety. Sub-Saharan Africa is a high-risk region
      for malaria, human immunodeficiency virus (HIV), hepatitis B virus and syphilis.
      Southeast Asia experiences high rates of hepatitis C virus. Areas with a tropical
      climate have an increased risk of Zika virus, Dengue virus, West Nile virus and
      Chikungunya, and impoverished countries face economical limitations which hinder
      efforts to acquire the most modern pathogen inactivation technology. These
      systems include Mirasol(r) Pathogen Reduction Technology, INTERCEPT(r), and
      THERAFLEX(r). Their procedures use a chemical and ultraviolet or visible light
      for pathogen inactivation and significantly decrease the threat of pathogen
      transmission in plasma and platelets. They are licensed for use in Europe and are
      used in several other countries. The current interest in the blood industry is
      the development of pathogen inactivation technologies that can treat whole blood
      (WB) and red blood cell (RBC). The Mirasol system has recently undergone phase
      III clinical trials for treating WB in Ghana and has demonstrated some efficacy
      toward malaria inactivation and low risk of adverse effects. A 2nd-generation of
      the INTERCEPT(r) S-303 system for WB is currently undergoing a phase III clinical
      trial. Both methodologies are applicable for WB and components derived from
      virally reduced WB or RBC.

PMID- 28488961
TI  - Effect of storage period of red blood cell suspensions on helper T-cell
      subpopulations.
AB  - BACKGROUND: The aim of this study was to investigate the immunological
      alterations that occur during the storage of erythrocyte suspensions which may
      lead to transfusion-related immunomodulation following allogeneic blood
      transfusion. MATERIALS AND METHODS: One part of the erythrocyte suspensions
      obtained from donors was leucoreduced while the other part was not. The
      leucoreduced (LR) and non-leucoreduced (NL) erythrocyte suspensions were then
      further divided into three equal amounts which were stored for 0, 21 or 42 days
      prior to measurements, by enzyme-linked immunosorbent assays, of cytokine levels
      in their supernatants. T-helper (Th) lymphocyte subgroups and gene expression
      were analysed in the NL erythrocyte suspensions by flow cytometry and real-time
      polymerase chain reaction, respectively. Results were compared to those of
      storage day 0. RESULTS: By day 21, the number of Th2 cells had increased
      significantly and the numbers of Th1, Th22 and Treg cells had decreased
      significantly in the NL erythrocyte suspensions. On day 42 the numbers of Th2 and
      Treg cells in the NL suspensions were significantly increased while the number of
      Th1 cells was significantly decreased. The levels of transcription factors
      (TBX21, GATA3, and SPI.1) were significantly decreased on days 21 and 42, and
      AHR, FOXP3 and RORC2 levels were significantly increased on day 42 in NL
      erythrocyte suspensions. The decrease in interleukin-22 and increase in
      transforming growth factor-beta levels found in NL erythrocyte suspensions on day
      21 were statistically significant. Elevated levels of interleukin-17A were found
      in both LR and NL erythrocyte suspensions on day 42. DISCUSSION: Our results
      suggest that allogeneic leucocytes and cytokines may play significant roles in
      the development of transfusion-related immunomodulation.

PMID- 28488962
TI  - Strategies for reducing the risk of transfusion-transmitted leishmaniasis in an
      area endemic for Leishmania infantum: a patient- and donor-targeted approach.
AB  - BACKGROUND: In the Balearic Islands, as in other areas of the Mediterranean
      basin, there is a significant proportion of asymptomatic Leishmania (L.) infantum
      infected blood donors, who may represent an important threat to transfusion
      safety. The Balearic Islands blood bank, located in an area endemic for L.
      infantum, carried out a study of donors and patients to investigate the impact of
      this infectious disease on blood safety in the region. MATERIALS AND METHODS:
      Twenty asymptomatic Leishmania-infected blood donors were followed-up between
      2008 and 2011 to investigate the evolution of Leishmania infection in
      asymptomatic carriers. Their blood was periodically tested for anti-Leishmania
      antibodies by western blot and for Leishmania DNA by quantitative polymerase
      chain reaction (qPCR). Additionally, the prevalence of L. infantum infection was
      investigated in a group of 68 multiply transfused patients to ascertain the risk
      of transfusion-transmitted leishmaniasis (TTL) in the region, taking into account
      regular blood component production practices such as pre-storage leucodepletion
      and pathogen reduction technology. RESULTS: All 20 donors remained asymptomatic
      over the study period (2008-2011). Most donors had repeatedly positive qPCR
      results, either persistently or intermittently, but showed no symptoms of
      Leishmaniasis. Levels of parasitaemia were remarkably low in asymptomatic donors,
      with values <=1 parasite/mL. Despite multiple transfusions received over 15
      years, no transfused patient studied was infected with L. infantum. DISCUSSION:
      L. infantum-infected donors can remain asymptomatic for at least 3 years. In our
      region, no cases of TTL were detected, despite an active search in multiply
      transfused patients. This seems to be related to two independent variables: (i) a
      low concentration of the parasite in the peripheral blood of asymptomatic
      carriers and (ii) the application of methods with proven efficacy against TTL,
      such as leucodepletion and pathogen reduction technology.

PMID- 28488963
TI  - Towards the implementation of patient blood management across Europe.

PMID- 28488964
TI  - Passive haemovigilance of blood components treated with a riboflavin-based
      pathogen reduction technology.

PMID- 28488965
TI  - Mild-to-moderate foeto-maternal haemorrhage in the third trimester and at term of
      pregnancy: quantitative determination and clinical-diagnostic evaluation.
AB  - BACKGROUND: Foeto-maternal haemorrhage (FMH), a gestational event that occurs
      before or during delivery, consists of a loss of foetal blood into the maternal
      circulation. FMH occurs more frequently during the third trimester or labour both
      in normal and complicated pregnancies. In the case of alloimmunisation, the
      maternal immunological response and the severity of the resulting foetal or
      neonatal disease depend on the amount of foetal blood that passes into the
      maternal circulation. The aim of this study was to determine FMH in the third
      trimester and at term of pregnancy and to evaluate the role of clinical and
      ultrasound markers in the prediction of FMH. MATERIALS AND METHODS: FMH was
      quantified by cytofluorimetric testing at 28 to 35 weeks of gestation in 223
      women and at term in 465 women, all with risk factors. Foetal evaluation included
      foetal movement profile, middle cerebral artery peak velocity of systolic blood
      flow (MCA-PSV) and cardiotocographic monitoring. RESULTS: All women tested
      negative for FMH in the third trimester. Four patients (0.9%) tested positive at
      term, with estimated volumes of bleeding of 2.2, 8.1, 12.3 and 39.8 mL. Three FMH
      cases (75%) had a non-reassuring cardiotocography compared to 8.9% (42/461) of
      women without FMH (p=0.003) and two FMH cases reported a reduction in foetal
      movements reduction compared to four of those without FMH (p=0.001). Mean MCA-PSV
      was normal in both the groups with and without FMH (p=0.22). DISCUSSION: FMH is
      rare in pregnancy and at term. Cytofluorimetric testing is a specific method to
      detect mild-to-moderate FMH even when the MCA-PSV is not informative. Mild-to
      moderate FMH is significantly associated with reduced foetal movements and non
      reassuring cardiotocographic monitoring.

PMID- 28488966
TI  - Haemolysis, pure red cell aplasia and red cell antibody formation associated with
      major and bidirectional ABO incompatible haematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Acute and delayed haemolysis, alloimmunisation and pure red cell
      aplasia (PRCA) are potential complications after ABO incompatible haematopoietic
      stem cell transplantation (HSCT). The aims of this study were to investigate
      acute and delayed red blood cell (RBC) antibody-associated complications,
      including haemolysis, PRCA and alloimmunisation in major and bidirectional ABO
      incompatible HSCT. MATERIALS AND METHODS: We retrospectively examined the
      transplant courses of 36 recipients of bone marrow or peripheral blood stem cells
      from ABO incompatible donors and evaluated the current practice of performing
      plasmapheresis in patients with higher isoagglutinin titres. We investigated the
      role of ABO incompatibility in haematopoietic recovery, transfusion requirements,
      alloimmunisation and PRCA. RESULTS: Laboratory signs of acute haemolysis were
      noted in five (14%) patients, one (3%) of whom had clinically overt haemolysis.
      Patients with haemolysis had IgM titres >=1:8 and received >16 mL of RBC in the
      HSCT. In patients with higher titres, plasmapheresis performed prior to the
      transplant prevented acute haemolysis. Delayed haemolysis was not recorded in the
      follow up. Haematopoietic recovery and transfusion requirements did not differ
      notably between patients with and without haemolysis. De novo RBC antibodies were
      detected in two (5.5%) patients after HSCT, and PRCA was noted in one (3%)
      patient. DISCUSSION: Carried out with adequate graft processing, plasmapheresis
      and blood component support, haemolysis is not a common complication after HSCT.
      Our results confirm that the occurrence of haemolysis depends on larger RBC
      volumes and higher isoagglutinin titres. Despite the reduction of patients'
      isoagglutinin titres by plasmapheresis, we still noted a critical combination for
      the development of laboratory signs of haemolysis (IgM titre >=1:8 and RBC volume
      >16 mL). De novo immunisation to RBC antigens and PRCA are rare events following
      ABO incompatible HSCT.

PMID- 28488967
TI  - Purinergic control of red blood cell metabolism: novel strategies to improve red
      cell storage quality.
AB  - Transfusion of stored blood is regarded as one of the great advances in modern
      medicine. However, during storage in the blood bank, red blood cells (RBCs)
      undergo a series of biochemical and biomechanical changes that affect cell
      morphology and physiology and potentially impair transfusion safety and efficacy.
      Despite reassuring evidence from clinical trials, it is universally accepted that
      the storage lesion(s) results in the altered physiology of long-stored RBCs and
      helps explain the rapid clearance of up to one-fourth of long-stored RBCs from
      the recipient's bloodstream at 24 hours after administration. These
      considerations explain the importance of understanding and mitigating the storage
      lesion. With the emergence of new technologies that have enabled large-scale and
      in-depth screening of the RBC metabolome and proteome, recent studies have
      provided novel insights into the molecule-level metabolic changes underpinning
      the accumulation of storage lesions to RBCs in the blood bank and alternative
      storage strategies to mitigate such lesion(s). These approaches borrow from
      recent insights on the biochemistry of RBC adaptation to high altitude hypoxia.
      We recently conducted investigations in genetically modified mice and revealed
      novel insights into the role of adenosine signalling in response to hypoxia as a
      previously unrecognised cascade regulating RBC glucose metabolism and increasing
      O2 release, while decreasing inflammation and tissue injuries in animal models.
      Here, we will discuss the molecular mechanisms underlying the role of purinergic
      molecules, including adenosine and adenosine triphosphate in manipulating RBCs
      and blood vessels in response to hypoxia. We will also speculate about new
      therapeutic possibilities to improve the quality of stored RBCs and the prognosis
      after transfusion.

PMID- 28488968
TI  - Prevention of red cell storage lesion: a comparison of five different additive
      solutions.
AB  - BACKGROUND: In Europe, red cell concentrates (RCC) are usually stored in SAGM
      (saline-adenine-glucose-mannitol). During storage, in vitro red cell quality
      declines, including lowered energy status and increased cell lysis. Recently,
      several additive solutions (ASs), designed to diminish the decline in in vitro
      quality during storage, have been developed. These new solutions have mainly been
      developed to better maintain red blood cell (RBC) 2,3-biphosphoglycerate (2,3
      BPG) levels and energy status during storage. High levels of 2,3 BPG allow for
      better oxygen release while high energy status is necessary for function and
      survival of RBC in vivo. In a paired study design, RBC ASs were compared for
      their ability to provide improved in vitro quality during hypothermic storage.
      MATERIALS AND METHODS: For each experiment, 5 whole blood units held overnight
      were pooled and split. The whole blood units were processed according to the
      buffy coat method. RBCs were resuspended in either SAGM, PAGGSM, PAG3M, E-Sol 5
      or AS-7 and leucoreduced by filtration. RCCs were stored for eight weeks at 2-6 
      degrees C and sampled weekly for analysis of in vitro quality parameters.
      RESULTS: Red cell concentrates stored in PAG3M, E-Sol 5 and AS-7 showed
      significantly higher lactate production and higher levels of intracellular
      adenosine triphosphate (ATP) and total adenylate. 2,3 BPG levels rapidly declined
      during storage in SAGM and PAGGSM. The decline in 2,3 BPG was inhibited during
      storage in E-Sol 5 and AS-7, while in PAG3M, 2,3 BPG level increased above the
      initial level till day 35 and remained detectable till day 56. Haemolysis was
      comparable for all ASs until day 35, upon prolonged storage, haemolysis in SAGM
      was higher than with the other ASs. As compared to SAGM, storage in PAGGSM,
      PAG3M, E-Sol 5 and AS-7 better maintained morphological properties. DISCUSSION:
      Storage of RBCs in the new generation ASs yield RBCs with more stable metabolite
      levels and improved overall quality during storage as compared with RBCs stored
      in SAGM.

PMID- 28488969
TI  - A cost analysis of public cord blood banks belonging to the Italian Cord Blood
      Network.
AB  - BACKGROUND: Public cord blood banking is currently managed in Italy by a network
      of 19 regional cord blood banks coordinated by the National Blood Centre and the
      National Transplant Centre. A cost analysis was carried out within the Italian
      network to determine the relationship between cost of cord blood collection and
      banking and size of the bank inventory, which ranged from 106 to 9,341 units on
      December 31st, 2012. MATERIALS AND METHODS: The 19 banks were invited to report
      costs incurred in 2012 related to cord blood unit collection, transportation,
      biological validation, characterisation, manipulation, cryopreservation, storage,
      data management, and general costs. Missing information on selected items was
      replaced with standardised costs represented by average data obtained from the
      reporting banks. Eight banks (52%) participated in the study. Average costs were
      determined in the three banks with inventories of >3,000 units vs the three banks
      with inventories of <1,000 units. RESULTS: Both cord blood collection and cord
      blood banking costs per unit were lower in the larger banks than in the smaller
      banks (average collection costs: ? 119.25 and ? 151.31, respectively; average
      banking costs: ? 3,614.15 and ? 8,158.37, respectively). DISCUSSION: The study
      outlined an inverse relationship between the costs of cord blood collection and
      banking and the size of the bank inventory, suggesting that scale economies could
      be obtained through centralisation of banking activities.

PMID- 28488970
TI  - Is it time to re-think a sustainable banking model for the Italian Cord Blood
      Network?

PMID- 28488971
TI  - Quality assessment and transfusion efficacy of buffy coat-derived platelet
      concentrates washed with platelet additive solution.
AB  - BACKGROUND: Transfusion of washed platelet concentrates (W-PC) is recommended for
      some patients, such as those who have had previous severe allergic transfusion
      reactions. However, we still lack a standardised method for preparing these
      products. Here, we assessed the effect of a manual washing procedure on in vitro
      platelet quality and on the transfusion efficacy of W-PCs. MATERIALS AND METHODS:
      Buffy coat-derived W-PC in Composol solution were prepared by one-step
      centrifugation. Platelet activation and function were evaluated before and after
      washing by means of: (i) CD62 expression by flow cytometry; (ii) platelet
      aggregation (LTA); and (iii) the VerifyNow(r) P2Y12 test. A pilot prospective
      transfusion study was carried out in 11 onco-hematology patients receiving, in a
      short time, two consecutive transfusions: one with standard PC (S-PC) and one
      with W-PC. The post-transfusion platelet increment, the 1 h and 24 h corrected
      count increment (CCI) and occurrence of bleeding events were used as indices of
      transfusion efficacy. RESULTS: Platelet recovery in W-PC was 84.8+/-5.4%. Washing
      slightly increased platelet activation in W-PC vs pre-washed samples (% CD62+
      platelets 23.6+/-7 vs 14.8+/-1; p=0.03). As compared to prewash samples, platelet
      reactivity of W-PC as measured by VerifyNow(r) P2Y12 was significantly lower with
      ADP (PRU 32.2+/-37.7 vs 4.2+/-2.4, p=0.027), but similar using TRAP. Platelet
      aggregation responses to TRAP, collagen, ristocetin and arachidonic acid were
      maintained in W-PC. The pilot transfusion trial showed similar 1 h (13.5+/-5.6 vs
      11.5+/-7.3, p=0.49) and 24 h (11+/-7.2 vs 9+/-6.5, p=0.48) CCI for S-PC and W-PC.
      Transfusion of W-PC was not associated with an increased number of bleeding
      events. DISCUSSION: We have set up a simple method to obtain buffy-coat-derived W
      PC, which has minor effects on in vitro platelet quality and transfusion
      effectiveness. This procedure can be easily implemented in transfusion centres
      for on-demand preparation of washed platelets.

PMID- 28488972
TI  - Clinically relevant non-major bleeding with oral anticoagulants: non-major may
      not be trivial.

PMID- 28488973
TI  - A pathogen reduction clinical trial in retrospect.

PMID- 28488974
TI  - Blood donor deferral policies across Europe and characteristics of men whohave
      sex with men screened for human immunodeficiency virus in bloodestablishments:
      data from the European Men-who-have-sex-with-men Internet Survey (EMIS).
AB  - BACKGROUND: The predominant mode of transmission of human immunodeficiency virus
      (HIV) in Europe is male-to-male transmission. Men who have sex with men (MSM) are
      deferred from donating blood in many countries, but nevertheless do donate blood.
      Based on data from 34 countries, we estimated the proportion of MSM screened for
      HIV in the context of a blood donation and identified individual factors
      associated with this HIV screening in order to propose possible public health
      interventions. MATERIALS AND METHODS: In 2010, the first European MSM Internet
      Survey (EMIS) collected self-reported data on HIV testing from >180,000 MSM in 38
      European countries. Using logistic regression, demographic and behavioural
      factors associated with screening for HIV in blood establishments were
      identified. Stratified by European sub-region, we analysed the proportion of MSM
      screening in blood establishments by time elapsed since last negative HIV test.
      RESULTS: Donor eligibility criteria for MSM vary across Europe with most
      countries using permanent deferral. The Western region had the lowest (2%)
      proportion of MSM screened in blood establishments and the Northeastern region
      had the highest (14%). Being <25 years old, not disclosing sexual attraction to
      men, never having had anal intercourse with a man, having a female partner,
      living in a rural area, and certain European sub-regions or countries of
      residence increased the likelihood of being screened in blood establishments.
      DISCUSSION: In spite of deferral policies, MSM are screened for HIV in the
      context of blood donations. Gay-friendly testing services are rare in rural
      areas, and young men might be reluctant to disclose their sexual orientation.
      Recent developments, such as home sampling, might offer new testing possibilities
      for those not reached by established services yet wishing to know their HIV
      status. Donor selection procedures should be improved. Both interventions might
      help to further reduce the risk of transfusion-transmitted infections.

PMID- 28488975
TI  - The Italian Regulatory Guidelines for the implementation of Patient Blood
      Management.

PMID- 28488976
TI  - Haemophilia A: the consequences of de novo mutations. Two case reports.

PMID- 28488977
TI  - Non-invasive foetal RhD genotyping to guide anti-D prophylaxis: an external
      quality assurance workshop.

PMID- 28488978
TI  - Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis and Treatment With a
      Biologic: A Case Report.
AB  - INTRODUCTION: One of the most dangerous dermatologic emergencies is Stevens
      Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN). Although a rare disease,
      it can often lead to significant mortality. CASE PRESENTATION: In this case
      report, we present a 77-year-old man who developed a sloughing rash that was
      secondary to a nonsteroidal anti-inflammatory drug. In addition to the
      recommended supportive care, the patient was treated with etanercept, a new, less
      commonly used intervention. DISCUSSION: We provide a brief review of SJS/TEN.
      Nonsteroidal anti-inflammatory drugs are a rare cause of SJS/TEN, and
      additionally, the use of biologics is a novel treatment modality for SJS/TEN.

PMID- 28488979
TI  - An Unlikely Rapid Transformation of Myelodysplastic Syndrome to Acute Leukemia: A
      Case Report.
AB  - INTRODUCTION: Myelodysplastic syndrome is characterized by stem-cell-derived
      clonal myelopoiesis with an alteration in proliferation and differentiation. This
      condition carries a potential for transformation to acute leukemia, primarily in
      cases that are accompanied by high-risk features at diagnosis. CASE PRESENTATION:
      A 68-year-old man with recently diagnosed myelodysplastic syndrome and Sweet
      syndrome (acute febrile neutrophilic dermatosis) presented to our Emergency
      Department with shortness of breath. During his hospital course, he developed
      signs and symptoms, predominantly consisting of respiratory difficulties, that
      were not typically characteristic of transformation to acute leukemia. Several
      days into his hospitalization, it was determined that the patient's underlying
      hematologic process seemed to have rapidly evolved into an acute myeloid
      leukemia, which accounted for the progression of symptoms. This patient
      ultimately opted for comfort measures only and died shortly thereafter.
      DISCUSSION: Two important factors stood out as representing an atypical
      presentation. First, this patient lacked any of the high-risk features of
      myelodysplastic syndrome that typically portend transformation. In addition, his
      progression to acute leukemia in 28 days from the time of diagnosis was far more
      rapid than the 274-day median previously described in the literature. We theorize
      that the presence of Sweet syndrome may have served as a predisposing factor to
      transformation. This finding may offer benefit to physicians to potentially
      better predict this outcome and pursue more aggressive treatment measures earlier
      in the course of the disease in such a setting.

PMID- 28488980
TI  - Response to Functional Medicine Case Study and Editorial.

PMID- 28488981
TI  - A Survey of Parents with Children on the Autism Spectrum: Experience with
      Services and Treatments.
AB  - INTRODUCTION: Autism spectrum disorders (ASD) are lifelong neurodevelopmental
      disorders, and little is known about how parents address the health and
      psychosocial consequences of ASD. Few studies have examined use of various
      treatments and services in a large, diverse sample of children with ASD and their
      families. OBJECTIVE: This paper presents methods to create an autism research
      resource across multiple large health delivery systems and describes services and
      treatments used by children with ASD and their families. METHODS: Four study
      sites conducted a Web survey of parents of children and adolescents with ASD who
      were members of Kaiser Permanente. We tabulated data distributions of survey
      responses and calculated chi2 statistics for differences between responders and
      nonresponders. RESULTS: The children of the 1155 respondents were racially and
      ethnically diverse (55% white, 6% black, 5% Asian, 9% multiracial, 24% Hispanic)
      and representative of the total population invited to participate with respect to
      child sex (83% male), child age (57% < 10 years), and ASD diagnosis (64% autistic
      disorder). The most frequently used services and treatments were Individualized
      Education Programs (85%), family physician visits (78%), and occupational and
      speech therapy (55% and 60%, respectively). Home-based programs frequently
      included implementation of social skills training (44%) and behavior management
      (42%). Prescription medication use was high (48%). Caregivers reported disruption
      of personal and family routines because of problem behaviors. CONCLUSION: These
      survey data help to elucidate parents' experiences with health services for their
      children with ASD and serve as a potential resource for future research.

PMID- 28488982
TI  - Philanthropy and Beyond: Creating Shared Value to Promote Well-Being for
      Individuals in Their Communities.
AB  - Health care organizations can magnify the impact of their community service and
      other philanthropic activities by implementing programs that create shared value.
      By definition, shared value is created when an initiative generates benefit for
      the sponsoring organization while also generating societal and community benefit.
      Because the programs generate benefit for the sponsoring organizations, the
      magnitude of any particular initiative is limited only by the market for the
      benefit and not the resources that are available for philanthropy.In this article
      we use three initiatives in sectors other than health care to illustrate the
      concept of shared value. We also present examples of five types of shared value
      programs that are sponsored by health care organizations: telehealth, worksite
      health promotion, school-based health centers, green and healthy housing, and
      clean and green health services. On the basis of the innovativeness of health
      care organizations that have already implemented programs that create shared
      value, we conclude that the opportunities for all health care organizations to
      create positive impact for individuals and communities through similar programs
      is large, and the limits have yet to be defined.

PMID- 28488983
TI  - Effectiveness of Electrostimulation on Whole Salivary Flow Among Patients with
      Type 2 Diabetes Mellitus.
AB  - CONTEXT: Xerostomia and hyposalivation are associated with diabetes. Research is
      sparse regarding electrostimulation as a mainstream therapy for salivary gland
      hypofunction. OBJECTIVE: To clinically evaluate the effectiveness of
      transcutaneous electric nerve stimulation (TENS) therapy in stimulating whole
      salivary flow among patients with xerostomia and hyposalivation caused by
      diabetes mellitus. DESIGN: Forty patients between age 30 to 75 years with
      diabetes mellitus categorized as controlled or uncontrolled who had subjective
      symptoms of xerostomia and an objective sign of hyposalivation were included in a
      prospective study. MAIN OUTCOME MEASURES: Unstimulated saliva through the "low
      forced spitting" method and stimulated saliva collection using TENS were assessed
      and compared. Longer-term effects of TENS application were evaluated by recalling
      the patient 24 hours later. RESULTS: A statistically significant increase in
      stimulated whole saliva after TENS application in continuous mode (p < 0.001) was
      demonstrated compared with unstimulated saliva, especially in xerostomic patients
      with diabetes. Burst mode inferred a statistically significant decrease in
      salivary flow (p < 0.001). CONCLUSION: In patients with diabetes with xerostomia
      and hyposalivation, TENS was highly effective in stimulating whole salivary flow.

PMID- 28488984
TI  - Research Letter: Anticholinergic Drugs and the Gallbladder -A Neglected Effect?

PMID- 28488985
TI  - An Alternative Paradigm for Evidence-Based Medicine: Revisiting Lawrence Weed,
      MD's Systems Approach.
AB  - Lawrence Weed, MD, is renowned for being the father of the Problem-Oriented
      Medical Record (POMR), the medical care standard for collecting, managing, and
      contextualizing patient data in medical records. What have been consistently
      overlooked are his teachings on knowledge coupling, which refers to matching
      patient data with associated medical knowledge. Together, the POMR standard and
      knowledge coupling are meant to form the basis of a systems approach that enables
      individualized evidence-based decision making within the context of
      multimorbidity and patient complexity.The POMR and knowledge coupling tools
      operationalize a problem-oriented model that reflects a sophisticated general
      systems theoretical approach to knowledge. This paradigm transcends reductionist
      approaches to knowledge by depicting how the meaning of specific entities (eg,
      disease constructs) and their associated probabilities can only be understood
      within their respective spatiotemporal and biopsychosocial relational contexts.
      Rigorous POMRs therefore require knowledge inputs from a network of
      interconnections among specific entities, which Dr Weed enabled through
      development of the Knowledge Net standard. The Knowledge Net's relational
      structure determines the applicability of knowledge within specific patient
      contexts. To enable the linkage of unique combinations of data in individual
      patient POMRs with existing medical knowledge structured in Knowledge Nets, Dr
      Weed developed the Knowledge Coupling standard.Dr Weed's standards for record
      keeping and knowledge coupling form the basis of a combinatorial approach to
      evidence-based medicine that fulfills Stange's call for a science of
      connectedness. Ensuing individualized processes of care become the dynamo
      powering a learning health care system that enables a co-construction of health
      premised on empowerment and intelligent human decision making, rather than
      promoting the artificial intelligence of tools. If the value of Engel's
      biopsychosocial model indeed relates to "guiding the parsimonious application of
      medical knowledge to the needs of each patient," Dr Weed's approach warrants
      serious consideration.

PMID- 28488986
TI  - Effect of a Smoking Cessation Program on Sexual Function Recovery Following
      Robotic Prostatectomy at Kaiser Permanente Southern California.
AB  - INTRODUCTION: The association between cigarette smoking and erectile dysfunction
      has been well established. Studies demonstrate improvements in erectile rigidity
      and tumescence as a result of smoking cessation. Radical prostatectomy is also
      associated with worsening of erectile function secondary to damage to the
      neurovascular bundles. To our knowledge, no previous studies have examined the
      relationship between smoking cessation after prostate cancer diagnosis and its
      effect on sexual function following robotic prostatectomy. We sought to
      demonstrate the utility of a smoking cessation program among patients with
      prostate cancer who planned to undergo robotic prostatectomy at Kaiser Permanente
      Southern California. METHODS: All patients who underwent robotic prostatectomy
      between March 2011 and April 2013 with known smoking status were included, and
      were followed-up through November 2014. All smokers were offered the smoking
      cessation program, which included wellness coaching, tobacco cessation classes,
      and pharmacotherapy. Patients completed the Expanded Prostate Cancer Index
      Composite-26 (EPIC-26) health-related quality-of-life (HR-QOL) survey at baseline
      and postoperatively at 1, 3, 6, 12, 18, and 24 months. There were 2 groups based
      on smoking status: Continued smoking vs quitting group. Patient's age, Charlson
      Comorbidity Score, body mass index, educational level, median household income,
      family history of prostate cancer, race/ethnicity, language, nerve-sparing
      status, and preoperative/postoperative clinicopathology and EPIC-26 HR-QOL scores
      were examined. A linear regression model was used to predict sexual function
      recovery. RESULTS: A total of 139 patients identified as smokers underwent the
      smoking cessation program and completed the EPIC-26 surveys. Fifty-six patients
      quit smoking, whereas 83 remained smokers at last follow-up. All demographics and
      clinicopathology were matched between the 2 cohorts. Smoking cessation, along
      with bilateral nerve-sparing status, were the only 2 modifiable factors
      associated with improved sexual function after prostatectomy (6.57 points, p =
      0.0226 and 8.97 points, p = 0.0485, respectively). CONCLUSION: In the setting of
      robotic prostatectomy, perioperative smoking cessation is associated with a
      significant improvement in long-term sexual functional outcome when other factors
      are adjusted.

PMID- 28488987
TI  - From the Bedside: A Family Physician Experiences Health Care from the Patient
      Side.

PMID- 28488988
TI  - Are They Too Old for Surgery? Safety of Cholecystectomy in Superelderly Patients
      (>= Age 90).
AB  - CONTEXT: Cholecystectomy is the most common general surgery procedure in patients
      older than age 65 years. By 2050, it is estimated that 2.0% of the population
      will be older than age 90 years. OBJECTIVE: To assess the mortality of
      cholecystectomy in superelderly patients (>= age 90 years). DESIGN: Using the
      American College of Surgeons National Surgical Quality Improvement Program
      database, a retrospective analysis was performed of superelderly patients who
      underwent laparoscopic and open cholecystectomy between 2005 and 2012. MAIN
      OUTCOME MEASURES: Thirty-day mortality. RESULTS: A total of 1007
      cholecystectomies were performed in superelderly patients between 2005 and 2012.
      Of these surgical procedures, 807 (80%) were nonemergent and 200 (20%) were
      performed emergently. Two hundred sixteen procedures (21.4%) were open and 791
      (78.6%) were laparoscopic. Mortality did not decrease significantly during the
      study period. The overall mortality was 5.5%, significantly less for the
      laparoscopic group (3.7% vs 12%, p < 0.001) and for the nonemergent group (4.5%
      vs 9.5%, p < 0.005). The median length of stay for open cholecystectomy was 9
      days compared with 5 days for laparoscopic (p < 0.001); for nonemergent
      cholecystectomy it was 5 days compared with 7 days for emergent cholecystectomy
      (p < 0.001). CONCLUSION: The mortality after cholecystectomy in superelderly
      patients did not change significantly during the study period. The mortality and
      morbidity for laparoscopic and elective procedures were significantly lower than
      for open procedures and for emergent procedures, respectively.

PMID- 28488989
TI  - Spice-y Kidney Failure: A Case Report and Systematic Review of Acute Kidney
      Injury Attributable to the Use of Synthetic Cannabis.
AB  - INTRODUCTION: Spice is a synthetic cannabinoid that is readily available for
      purchase in smoke shops at relatively low cost. Spice is not detectable upon
      routine drug screening, making it an increasingly popular new street drug. CASE
      REPORT: A 21-year-old man presented with new-onset seizures. During the next 2
      days, he developed uncontrollable hypertension, agitation, respiratory failure
      requiring intubation, pulmonary hypertension, and acute kidney injury (AKI) with
      a maximum blood urea nitrogen/creatinine level of 54/7.90 mg/dL. A complete renal
      workup was negative, but his urine sediment revealed granular casts. A discussion
      with family and friends revealed that this patient had smoked Spice during the
      last month. His renal function started to improve with supportive therapy, and
      his AKI resolved by the time of discharge without renal replacement therapy.
      DISCUSSION: Spice differs from marijuana because it is a cannabinoid receptor
      type 1 and 2 agonist. The pathologic mechanism of AKI remains unclear, but the
      condition likely is attributable to acute tubular necrosis or acute interstitial
      nephritis, as proven by biopsies performed in previous case series. It is
      important to raise awareness that a new Spice strain that may be circulating in
      the Southern California Inland Empire can endanger young users who may develop
      seizures, respiratory failure, and AKI.

PMID- 28488990
TI  - Patient and Practitioner Perspectives on Culturally Centered Integrated Care to
      Address Health Disparities in Primary Care.
AB  - INTRODUCTION: Addressing the multifaceted health and mental health needs of
      ethnically and culturally diverse individuals is a challenge within the current
      health care system. Integrated care provides a promising approach to improve
      mental health treatment-seeking disparities; however, adaptation of care models
      to impact African Americans is lacking. Although resources to support engagement
      of diverse populations in depression care exist, little has been developed to
      tailor patient preferences in accessing and engaging mental health services that
      are integrated into primary care. OBJECTIVE: Our research seeks to add a cultural
      focus to the existing literature concerning integrated health care models to help
      address depression and selected co-occurring chronic health conditions in primary
      care settings. METHODS: Thirty-two adult patients of an integrated primary care
      clinic participated in focus groups discussing their individual health
      experiences. Nine health care practitioners/administrators from five different
      integrated practice settings in the Atlanta, GA, area participated in key
      informant interviews. MAIN OUTCOME MEASURES: Transcripts were analyzed for key
      themes related to depression care, perceived unmet cultural needs, and desired
      adaptations. RESULTS: Common themes emerged such as the importance of peer
      support and community engagement as areas of patient interest. Participants had
      good knowledge in recognizing depressive symptoms but were less knowledgeable
      about treatment options and expectations of treatment. The administrative and
      practitioner perspective suggests that patient preferences are valued and
      perceived as valid. CONCLUSION: It is critical that strategies and models are
      developed to improve health care among underserved minorities because current
      models offer variable efficacy among this population.

PMID- 28488991
TI  - Geriatric Hip Fracture Care: Fixing a Fragmented System.
AB  - CONTEXT: Fragmentation in geriatric hip fracture care is a growing concern
      because of the aging population. Patients with hip fractures at our institution
      historically were admitted to multiple different services and units, leading to
      unnecessary variation in inpatient care. Such inconsistency contributed to delays
      in surgery, discharge, and functional recovery; hospital-acquired complications;
      failure to adhere to best practices in osteoporosis management; and poor
      coordination with outpatient practitioners. OBJECTIVE: To describe a stepwise
      approach to systems redesign for this patient population. DESIGN: We designed and
      implemented a comprehensive geriatric hip fracture program for patients aged 65
      years and older at our academic Medical Center in October 2014. Key interventions
      included admission of all ward-status patients to the Orthopedics Service with
      hospitalist comanagement; geographic placement on the Orthopedics Unit; and
      standardized, evidence-based electronic order sets bundling geriatric best
      practices and a streamlined workflow for discharge planning. MAIN OUTCOME
      MEASURES: Hospital length of stay. RESULTS: We identified 271 admissions among
      267 patients between January 1, 2012, and March 31, 2016; of those, 154 were
      before and 117 were after program implementation. Mean hospital length of stay
      significantly improved from 6.4 to 5.5 days (p = 0.004). The 30-day all-cause
      readmission rate and discharge disposition remained stable. The percentage of
      patients receiving osteoporosis evaluation and treatment increased significantly.
      The rate of completed 30-day outpatient follow-up also improved. CONCLUSION: Our
      comprehensive geriatric hip fracture program achieved and sustained gains in the
      quality and efficiency of care by improving fragmentation in the health care
      system.

PMID- 28488992
TI  - Image Diagnosis: Splenic Infarction Associated with Oral Contraceptive Pills in a
      Healthy Young Woman.

PMID- 28488993
TI  - Physician Guide to Appropriate Opioid Prescribing for Noncancer Pain.
AB  - Prescription opioid use for relief of noncancer pain has risen dramatically in
      the last 15 years, contributing to a quadrupling of opioid overdoses and
      prescription opioid-related deaths. This crisis is resulting in heightened
      attention by health care professionals and organizations, law enforcement, and
      the government. In this article, I highlight key topics in the management of
      patients using opioids (or potentially needing opioids) in outpatient clinical
      practice; federal and state law enforcement actions regarding physicians' illegal
      prescribing of opioids; multimodal approaches to pain control; nonmedication
      management of pain; response strategies when suspecting a patient of diverting or
      misusing opioids; and warning signs for abuse or diversion. For those patients
      for whom opioids are appropriate, I describe key elements for prescribing,
      including documentation of a detailed history and examination, appropriate
      evaluation to arrive at a specific diagnosis, individualizing management, and
      ongoing monitoring (including the use of urine drug screening and a prescription
      drug monitoring program). In addition to individual action, when possible, the
      initiation of systemwide and clinicwide safe prescribing practices supports the
      physician and patient such that the patient's well-being is at the heart of all
      pain management decisions. Physicians are encouraged to further educate
      themselves to treat pain safely and effectively; to screen patients for opioid
      use disorder and, when diagnosed, to connect them with evidence-based treatment;
      and to follow Centers for Disease Control and Prevention guidelines whenever
      possible.

PMID- 28488994
TI  - Establishing and maintaining the National Vaccination Register in Finland.
AB  - Computerised, population-based vaccination registers are valuable tools for
      assessing the vaccine uptake and impact in populations. However, reliable impact
      assessment is only possible if the data quality can be reviewed and monitored
      continuously. This report describes the establishment and maintenance of the
      National Vaccination Register (NVR) in Finland. Currently, the NVR covers
      nationwide records of vaccinations given within the frame of the National
      Vaccination Programme since 2009. All vaccinations registered in the NVR contain
      a record of the personal identity code, the administered vaccine, and the date of
      vaccination. The vaccine lot number is the key component for recording and
      identifying vaccinations, because of its broad availability across patient
      information systems and its importance in vaccine safety monitoring. Vaccination
      records are accumulated and updated daily into the NVR, and their completeness is
      monitored monthly to assess deficiencies in data entry and data collection.
      Additionally, an alert system reports unexpected changes in data accumulation
      prompting the validation of observed changes in vaccination coverage. The
      presented process documentation may serve as basis to improve the design and
      quality of other vaccination or healthcare registers and aims to inspire the set
      up of vaccination registers in those countries which still do not have one.

PMID- 28488995
TI  - Written reminders increase vaccine coverage in Danish children - evaluation of a
      nationwide intervention using The Danish Vaccination Register, 2014 to 2015.
AB  - We evaluated a national intervention of sending written reminders to parents of
      children lacking childhood vaccinations, using the Danish Vaccination Register
      (DDV). The intervention cohort included the full birth cohort of 124,189 children
      born in Denmark who reached the age of 2 and 6.5 years from 15 May 2014 to 14 May
      2015. The reference cohort comprised 124,427 children who reached the age of 2
      and 6.5 years from 15 May 2013 to 14 May 2014. Vaccination coverage was higher in
      the intervention cohort at 2.5 and 7 years of age. The differences were most
      pronounced for the second dose of the measles-mumps-rubella vaccine (MMR2) and
      the diphtheria-tetanus-pertussis-polio vaccine DTaP-IPV4 among the 7-year-olds,
      with 5.0 percentage points (95% confidence interval (CI): 4.5-5.4) and 6.4
      percentage points (95% CI: 6.0-6.9), respectively. Among the 2.5 and 7-year-olds,
      the proportion of vaccinations in the preceding 6 months was 46% and three times
      higher, respectively, in the intervention cohort than the reference cohort. This
      study indicates a marked effect of personalised written reminders, highest for
      the vaccines given later in the schedule in the older cohort. In addition, the
      reminders increased awareness about correct registration of vaccinations in DDV.

PMID- 28488996
TI  - Assessing varicella vaccine effectiveness and its influencing factors using
      health insurance claims data, Germany, 2006 to 2015.
AB  - In Germany, routine childhood varicella vaccination was implemented in 2004 with
      two doses recommended since 2009. We used an immunisation information system
      based on countrywide health insurance claims data to analyse vaccine
      effectiveness (VE) and factors influencing VE. We applied proportional hazard
      models to estimate VE under various conditions and compared the risk of acquiring
      varicella among unvaccinated children in regions with high vs low vaccination
      coverage (VC). Among 1.4 million children we identified 29,404 varicella cases
      over a maximum follow-up of 8 years post-vaccination. One-dose VE was 81.9% (95%
      confidence interval (CI): 81.4-82.5), two-dose VE 94.4% (95% CI: 94.2-94.6). With
      dose one given 1-27 days after measles-containing vaccine (MCV), one-dose VE was
      32.2% (95% CI: 10.4-48.6), two-dose VE 92.8% (95% CI: 84.8-96.6). VE was not
      associated with age at vaccination (11-14 vs >= 15 months), time since
      vaccination, or vaccine type. Unvaccinated children had a twofold higher risk of
      acquiring varicella in low VC regions. Our system generated valuable data,
      showing that two-dose varicella vaccination provides good protection for at least
      8 years. Unvaccinated children benefit from herd effects. When the first
      varicella vaccine dose is given shortly after MCV, a second dose is essential.

PMID- 28488997
TI  - Registries: An essential tool for maximising the health benefits of immunisation
      in the 21st century.

PMID- 28488998
TI  - Ongoing measles outbreak in Wallonia, Belgium, December 2016 to March 2017:
      characteristics and challenges.
AB  - We describe characteristics of an ongoing measles outbreak in Wallonia, Belgium,
      and difficulties in control measures implementation. As at 12 March 2017, 177
      measles cases were notified, of which 50% were 15 years and older, 49% female.
      Atypical clinical presentation and severe complications, mainly among adults, in
      combination with late notification, low or unknown vaccination coverage of
      contacts, infected healthcare workers and increased workload due to contact
      tracing, are the main concerns for outbreak management.

PMID- 28488999
TI  - Immunisation Information Systems - useful tools for monitoring vaccination
      programmes in EU/EEA countries, 2016.
AB  - Immunisation Information Systems (IIS) are computerised confidential population
      based-systems containing individual-level information on vaccines received in a
      given area. They benefit individuals directly by ensuring vaccination according
      to the schedule and they provide information to vaccine providers and public
      health authorities responsible for the delivery and monitoring of an immunisation
      programme. In 2016, the European Centre for Disease Prevention and Control (ECDC)
      conducted a survey on the level of implementation and functionalities of IIS in
      30 European Union/European Economic Area (EU/EEA) countries. It explored the
      governance and financial support for the systems, IIS software, system
      characteristics in terms of population, identification of immunisation
      recipients, vaccinations received, and integration with other health record
      systems, the use of the systems for surveillance and programme management as well
      as the challenges involved with implementation. The survey was answered by 27 of
      the 30 EU/EEA countries having either a system in production at national or
      subnational levels (n = 16), or being piloted (n = 5) or with plans for setting
      up a system in the future (n = 6). The results demonstrate the added-value of IIS
      in a number of areas of vaccination programme monitoring such as monitoring
      vaccine coverage at local geographical levels, linking individual immunisation
      history with health outcome data for safety investigations, monitoring vaccine
      effectiveness and failures and as an educational tool for both vaccine providers
      and vaccine recipients. IIS represent a significant way forward for life-long
      vaccination programme monitoring.

PMID- 28489000
TI  - Suboptimal MMR2 vaccine coverage in six counties in Norway detected through the
      national immunisation registry, April 2014 to April 2017.
AB  - In 2014, Norway became aware of potential low vaccination coverage for the second
      dose of measles-mumps-rubella vaccine (MMR2) in six of 19 counties. This was
      detected by comparing the national coverage (NC) for 16-year-olds extracted from
      the national immunisation registry SYSVAK with the annual status update for
      elimination of measles and rubella (ASU) reported to the World Health
      Organization (WHO). The existing method for calculating NC in 2014 did not show
      MMR2 coverage. ASU reporting on MMR2 was significantly lower then the NC and
      below the WHO-recommended 95% coverage. SYSVAK is based on the Norwegian personal
      identification numbers, which allows monitoring of vaccinations at aggregateded
      as well as individual level. It is an important tool for active surveillance of
      the performance of the Norwegian Childhood Immunisation Programme (NCIP). The
      method for calculating NC was improved in 2015 to reflect MMR2 coverage for 16
      year-olds. As a result, Norway has improved its real-time surveillance and
      monitoring of the actual MMR2 coverage also through SYSVAK (the annual
      publication of NC). Vaccinators receive feedback for follow-up if 15-year-olds
      are missing MMR2. In 2017, only three counties had an MMR2 coverage below 90%.

PMID- 28489001
TI  - Noradrenaline blockade specifically enhances metacognitive performance.
AB  - Impairments in metacognition, the ability to accurately report one's performance,
      are common in patients with psychiatric disorders, where a putative
      neuromodulatory dysregulation provides the rationale for pharmacological
      interventions. Previously, we have shown how unexpected arousal modulates
      metacognition (Allen et al., 2016). Here, we report a double-blind, placebo
      controlled, study that examined specific effects of noradrenaline and dopamine on
      both metacognition and perceptual decision making. Signal theoretic analysis of a
      global motion discrimination task with adaptive performance staircasing revealed
      that noradrenergic blockade (40 mg propranolol) significantly increased
      metacognitive performance (type-II area under the curve, AUROC2), but had no
      impact on perceptual decision making performance. Blockade of dopamine D2/3
      receptors (400 mg amisulpride) had no effect on either metacognition or
      perceptual decision making. Our study is the first to show a pharmacological
      enhancement of metacognitive performance, in the absence of any effect on
      perceptual decision making. This enhancement points to a regulatory role for
      noradrenergic neurotransmission in perceptual metacognition.

PMID- 28489002
TI  - USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin
      homeostasis through Ubiquilin.
AB  - Synapse formation and growth are tightly controlled processes. How synaptic
      growth is terminated after reaching proper size remains unclear. Here, we show
      that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In
      leon mutants, postsynaptic specializations of neuromuscular junctions are
      dramatically expanded, including the subsynaptic reticulum, the postsynaptic
      density, and the glutamate receptor cluster. Expansion of these postsynaptic
      features is caused by a disruption of ubiquitin homeostasis with accumulation of
      free ubiquitin chains and ubiquitinated substrates in the leon mutant.
      Accumulation of Ubiquilin (Ubqn), the ubiquitin receptor whose human homolog
      ubiquilin 2 is associated with familial amyotrophic lateral sclerosis, also
      contributes to defects in postsynaptic growth and ubiquitin homeostasis.
      Importantly, accumulations of postsynaptic proteins cause different aspects of
      postsynaptic overgrowth in leon mutants. Thus, the deubiquitinase Leon maintains
      ubiquitin homeostasis and proper Ubqn levels, preventing postsynaptic proteins
      from accumulation to confine postsynaptic growth.

PMID- 28489003
TI  - Odor identity coding by distributed ensembles of neurons in the mouse olfactory
      cortex.
AB  - Olfactory perception and behaviors critically depend on the ability to identify
      an odor across a wide range of concentrations. Here, we use calcium imaging to
      determine how odor identity is encoded in olfactory cortex. We find that, despite
      considerable trial-to-trial variability, odor identity can accurately be decoded
      from ensembles of co-active neurons that are distributed across piriform cortex
      without any apparent spatial organization. However, piriform response patterns
      change substantially over a 100-fold change in odor concentration, apparently
      degrading the population representation of odor identity. We show that this
      problem can be resolved by decoding odor identity from a subpopulation of
      concentration-invariant piriform neurons. These concentration-invariant neurons
      are overrepresented in piriform cortex but not in olfactory bulb mitral and
      tufted cells. We therefore propose that distinct perceptual features of odors are
      encoded in independent subnetworks of neurons in the olfactory cortex.

PMID- 28489005
TI  - [Long-term efficacy in clinical gene therapy[Editorial]].

PMID- 28489006
TI  - [TAVI: Advancements in treatment in Iceland and worldwide[Editorial]].

PMID- 28489007
TI  - [Frequency of symptoms and drug treatment among dying patients in the last 24
      hours of life at Landspitali - The National University Hospital of Iceland and in
      nursing homes].
AB  - INTRODUCTION: The purpose of this study was to evaluate the frequency of 5 common
      symptoms and drug treatments prescribed and given in the last 24 hours of life in
      11 medical units at Landspitali National University Hospital of Iceland (LUH) and
      in 7 nursing homes (NH). MATERIAL AND METHODS: Data was collected retrospectively
      from 232 charts of patients who died in 2012, using documentation in the
      Liverpool Care Pathway (LCP) and the medication management system. RESULTS: About
      half of the patients died at LUH with similar gender ratio but 70% of patients in
      NH were women. The LCP was used for 50% of all deaths at LUH and 58% in NH. In
      45% of all deaths LCP was used for 24 hours or less. The most common symptoms
      were pain (51%), agitation (36%) and respiratory tract secretions (36%).
      Frequency of symptoms was similar between institutions and age groups. Cancer
      patients had significantly higher incidence of agitation and were prescribed and
      given higher doses of morphine compared to other groups. Regular medication for
      agitation was haloperidol (45%), diazepam (40%) and midazolam (5%). Close to 70%
      of the patients were treated with a scopolamin patch for death rattle.
      CONCLUSION: A large number of patients have symptoms in the last 24 hours of life
      both in hospital and in nursing homes. Symptom control can be improved by
      adjusting morphine doses to patients need, using regular doses of benzodiazepine
      for agitation and better use of anticholinergic medication for death rattle. Key
      words: symptoms, medication, dying patients, last 24 hours of life, hospital,
      nursing homes. Correspondence: Svandis Iris Halfdanardottir,
      svaniris@landspitali.is.

PMID- 28489004
TI  - Analogous mechanism regulating formation of neocortical basal radial glia and
      cerebellar Bergmann glia.
AB  - Neocortical basal radial glia (bRG) and cerebellar Bergmann glia (BG) are basal
      progenitors derived from ventricular apical radial glia (aRG) that selectively
      lose their apical processes. bRG and BG have been implicated in the expansion and
      folding of the cerebrum and cerebellum, respectively. Here, we analyzed the
      molecular characteristics and development of bRG and BG. Transcriptomic
      comparison revealed striking similarity of the molecular features of bRG and BG.
      We found that heightened ERK signaling activity in aRG is tightly linked to the
      temporal formation and the relative abundance of bRG in human and mouse cortices.
      Forced activation of an FGF-ERK-ETV axis that is crucial to BG induction
      specifically induced bRG with canonical human bRG features in mice. Therefore,
      our data point to a common mechanism of bRG and BG generation, bearing
      implications to the role for these basal progenitors in the evolution of cortical
      folding of the cerebrum and cerebellum.

PMID- 28489008
TI  - [Do opioids, sedatives and proton-pump inhibitors increase the risk of
      fractures?]
AB  - INTRODUCTION: A pharmacoepidemiological study was conducted to analyse the
      relationship between bone fracture and the use of certain drugs.
      MATERIAL/METHODS: The study includes patients 40 years and older, diagnosed with
      bone fractures in the Emergency Department of Landspitali University Hospital in
      Reykjavik, Iceland, during a 10-year period (2002-2011). Also were included those
      who picked up from a pharmacy 90 DDD or more per year of the drugs included in
      the study in the capital region of Iceland during same period. Opiates,
      benzodiazepines/hypnotics (sedatives) were compared with HMG-CoA reductase
      inhibitors (statins), non-steroid anti-inflammatory drugs (NSAID) and beta
      blockers. Proton-pump inhibitors (PPI) and histamine H2-antagonists were also
      examined. To examine the association between above drugs and fractures the data
      from electronic hospital database were matched to the prescription database run
      by the Directorate of Health. RESULTS: A total of 29,056 fractures in 22,891
      individuals were identified. The females with fractures were significantly older
      and twice as many, compared to males. The odds ratio (OR) for fractures was not
      significantly different between the NSAID, statins and beta blockers. OR for
      opiates showed almost double increased risk of fractures, 40% increased risk for
      sedatives and 30% increased risk for PPIs compared to beta blockers. No increased
      fracture-risk was noted in patients taking H2 antagonists. CONCLUSION: This study
      shows a relationship between the use of opiates, sedatives and bone fractures.
      The incidence of fractures was also increased in patients taking PPIs which is
      interesting in the light of the wide-spread use of PPIs in the community. Key
      words: Opiates, sedatives, proton- pump inhibitors, fractures. Correspondence:
      Magnus Johannsson, magjoh@hi.is.

PMID- 28489009
TI  - [Vanishing lungs - a case report].
AB  - A 55 year old female with rheumatoid arthritis who was repeatedly admitted to
      internal medicine for fever, shortness of breath and pleuritic chest pain.
      Laboratory work up showed normal WBC but elevated CRP and sedimentatation rate.
      Cultures were negative. Imaging studies revealed elevated diaphragms, bilateral
      atelectasis and pleural fluid but normal lung parenchyma. Lung function testing
      showed restriction. Anti-dsDNA and anti-Ro/SSA were elevated. A clinical
      diagnosis of anti-TNF-induced lupus secondary to infliximab and shrinking lung
      syndrome was made. The patient showed improvement on steroids but subsequent
      worsening when tapered. Rituximab was then initiated with good results. Key
      words: rheumatoid arthritis, infliximab, restrictive lung disease, shrinking lung
      syndrome, anti-TNF induced lupus. Correspondence: Thorunn Halldora Thordardottir,
      thorhtho@landspitali.is.

PMID- 28489010
TI  - [New government, new health policy?[Editorial]].

PMID- 28489011
TI  - [The Icelandic organ donation law: has the time arrived for presumed
      consent?[Editorial]].

PMID- 28489012
TI  - [Icelanders' beliefs about medicines. Use of BMQ].
AB  - OBJECTIVE: To study beliefs held by the general public in Iceland about
      medicines. METHODS: The Beliefs about Medicines Questionnaire was used to explore
      Icelanders' beliefs about medicines. A sample of 1500 Icelandic citizens, aged 18
      75, obtained from the Social Science Research Insti-tute was given The Beliefs
      about Medicines Questionnaire. RESULTS: The response rate was 61.6%. Most
      Icelanders have positive beliefs about their medication as well as general trust.
      Those who suffer from chronic diseases are more positive towards medicines than
      others and less inclined to view them as excessively used and harmful. Higher
      level of education predicts more positive beliefs towards medication - and vice
      versa. Gender and age do not seem to affect such beliefs. CONCLUSION: Gaining a
      better understanding of people's beliefs about medicines and what determines
      these beliefs can be of considerable value in the search for ways to improve
      therapy and adherence, espe-cially for those suffering from chronic diseases.
      Promoting education for the general public about medicines might result in less
      mis-understanding among patients and subsequently better grounded -beliefs and
      more adequate therapeutic adherence. Key words: beliefs, medicines, Icelanders,
      BMQ, survey. Correspondence: Hlif Vilhelmsdottir, hlif84@gmail.com.

PMID- 28489014
TI  - [Surgical treatment for endocarditis in Iceland 1997-2003].
AB  - INTRODUCTION: The aim of this study was to evaluate the outcomes of operations
      for endocarditis in Iceland, but such results have not been reported before.
      MATERIALS AND METHODS: Retrospective nation-wide study of pa--tients that
      underwent open-heart surgery for infective endocarditis at Landspitali University
      Hospital in 1997-2013. Variables were collected from hospital charts. Long-term
      survival was analysed using Kaplan- Meier methods. Mean follow-up time was 7.2
      years. RESULTS: Out of 179 patients diagnosed with endocarditis, 38 (21%) 
      underwent open heart surgery. Two patients were excluded due to missing
      information leaving 36 patients for analysis. The number of operations steadily
      increased, or from 8 to 21 during the first and last 5-years of the study period
      (OR: 1.12, 95% CI: 1.05-1.21, p=0.002). The most common pathogen was S. aureus
      and 81% (29/36) of the patients had positive blood cultures. Three patients had
      history of previous cardiac surgery and five had history of intravenous drug
      abuse. The aortic valve was most often infected (72%), followed by the mitral
      valve (28%). The infected valve was replaced in 35 cases 14 with a mechanical
      prosthesis and 20 with a bioprosthesis. In addition two mitral valves were
      repaired. Postoperative complications included perioperative myocardial
      infarction (35%), respiratory failure (44%) and reoperation for bleeding (25%).
      Thirty-day mortality was 11% (4 patients) with 5- and 10-year survival of 59% and
      49%, respectively. CONCLUSION: One out of five patients with endocarditis
      underwent surgery, most commonly aortic or mitral valve replacement. Outcomes
      were comparable to other studies. In comparison to elective valve replace-ment
      surgery the rate of post-operative complications and 30-day mortality were higher
      and long-term survival was less favorable. Key words: Endocarditis, surgical
      treatment, valve replacement, complications, outcome. Correspondence: Arnar
      Geirsson, arnargeirsson@yahoo.com.

PMID- 28489013
TI  - [Incidence, cause and treatment of colonic perforations in Iceland 1998-2007: A
      nationwide study].
AB  - INTRODUCTION: Colon perforation is a serious illness with mortality reported from
      0-39%. Surgery used to be the gold standard but treatment has changed as studies
      have indicated comparable results with less invasive treatment. The aim of this
      study was to evaluate the incidence of acute colon perforations in Iceland,
      causes and treatment. MATERIAL AND METHODS: A retrospective, nationwide,
      multicenter analysis was performed based on ICD-10 codes from databases of the
      main hospitals in Iceland. Age, gender, year of perforation, cause, means of
      diagnosis, treatment and outcome were registered. Patients under 18 years and
      post mortem diagnosis were excluded. RESULTS: 225 patients met criteria, 131
      women (58%) and 94 men (42%), median age 70 years (range 30-95). The most common
      causes were diverticulitis (67%), colonoscopy (12%) and complications during
      operations (5%). During the first five study years, 27% received conservative
      treatment while 71% underwent surgery. By the end of the study era this ratio was
      45% and 54% respectively. The rate of permanent stoma was 10%. CONCLUSIONS:
      Diverticulitis was the most common cause of colon perforation in Iceland during
      the study period. Many patients still undergo surgery but there has been a
      dramatic change toward more conservative treatment. The rate of stoma closure is
      comparable to studies elsewhere. 1University Hospital of Iceland, Dept. General
      Surgery, 2University of Iceland, Faculty of Medicine, 3Akureyri Teaching
      Hospital, 4Akranes Hospital and Health Care Center, Iceland. Key words: Colon
      perforation, diverticulitis, Hartmann's reversal. Correspondence: Elsa B.
      Valsdottir, elsava@landspitali.is.

PMID- 28489015
TI  - Tracking the evolution of causal cognition in humans.
AB  - We suggest a seven-grade model for the evolution of causal cognition as a
      framework that can be used to gauge variation in the complexity of causal
      reasoning from the panin-hominin split until the appearance of cognitively modern
      hunter-gatherer communities. The intention is to put forward a cohesive model for
      the evolution of causal cognition in humans, which can be assessed against
      increasingly fine-grained empirical data from the palaeoanthropological and
      archaeological records. We propose that the tracking behaviour (i.e., the ability
      to interpret and follow external, inanimate, visual clues of hominins) provides a
      rich case study for tracing the evolution of causal cognition in our lineage. The
      grades of causal cognition are tentatively linked to aspects of the Stone
      Age/Palaeolithic archaeological record. Our model can also be applied to current
      work in evolutionary psychology and research on causal cognition, so that an
      inter-disciplinary understanding and correlation of processes becomes
      increasingly possible.

PMID- 28489016
TI  - Carbon nanotube entangled Mn3O4 octahedron as anode materials for lithium-ion
      batteries.
AB  - A nanocomposite of Mn3O4 octahedrons entangled by carbon nanotubes (CNTs) was
      synthesized by a hydrothermal method assisted with a non-ionic surfactant. The
      integration of octahedral structure and CNTs could offer many critical features,
      which are needed for high activity anodes, such as fast ion diffusion, good
      electronic conductivity, and skeleton supporting function, thus enabling the
      nanocomposite-based anodes with excellent electrochemical performance. In
      addition, CNTs can not only serve as the conductive network and structure
      skeleton to improve the anode performance, but also play an indispensable role in
      the formation of more uniform Mn3O4 octahedrons. The lithium-ion batteries based
      on the CNTs-entangled Mn3O4 octahedrons delivered a high capacity of over 800 mAh
      g-1 at a current density of 0.2 C for 200 cycles, and even as high as 678.4 mAh g
      1 when cycled at 0.5 C after 400 cycles, exhibiting a high capability and
      ultralong cycle life.

PMID- 28489017
TI  - Corrigendum:(2013 Nanotechnology {?bf 24} 395702)]{Corrigendum: Frequency tuning,
      nonlinearities and mode coupling in circular mechanical graphene resonators (2013
      Nanotechnology {?bf 24} 395702).
AB  - N/A.

PMID- 28489018
TI  - Estimating sleep parameters using nasal pressure signals applicable to continuous
      positive airway pressure devices.
AB  - OBJECTIVE: This paper proposes a method for classifying sleep-wakefulness and
      estimating sleep parameters using nasal pressure signals applicable to a
      continuous positive airway pressure (CPAP) device. APPROACH: In order to classify
      the sleep-wakefulness states of patients with sleep-disordered breathing (SDB),
      apnea-hypopnea and snoring events are first detected. Epochs detected as SDB are
      classified as sleep, and time-domain- and frequency-domain-based features are
      extracted from the epochs that are detected as normal breathing. Subsequently,
      sleep-wakefulness is classified using a support vector machine (SVM) classifier
      in the normal breathing epoch. Finally, four sleep parameters-sleep onset, wake
      after sleep onset, total sleep time and sleep efficiency-are estimated based on
      the classified sleep-wakefulness. In order to develop and test the algorithm, 110
      patients diagnosed with SDB participated in this study. Ninety of the subjects
      underwent full-night polysomnography (PSG) and twenty underwent split-night PSG.
      The subjects were divided into 50 patients of a training set (full/split: 42/8),
      30 of a validation set (full/split: 24/6) and 30 of a test set (full/split:
      24/6). MAIN RESULTS: In the experiments conducted, sleep-wakefulness
      classification accuracy was found to be 83.2% in the test set, compared with the
      PSG scoring results of clinical experts. Furthermore, all four sleep parameters
      showed higher correlations than the results obtained via PSG (r  ?  0.84, p  < 
      0.05). In order to determine whether the proposed method is applicable to CPAP,
      sleep-wakefulness classification performances were evaluated for each CPAP in the
      split-night PSG data. The results indicate that the accuracy and sensitivity of
      sleep-wakefulness classification by CPAP variation shows no statistically
      significant difference (p  <  0.05). SIGNIFICANCE: The contributions made in this
      study are applicable to the automatic classification of sleep-wakefulness states
      in CPAP devices and evaluation of the quality of sleep.

PMID- 28489019
TI  - Heart sound classification from unsegmented phonocardiograms.
AB  - OBJECTIVE: Most algorithms for automated analysis of phonocardiograms (PCG)
      require segmentation of the signal into the characteristic heart sounds. The aim
      was to assess the feasibility for accurate classification of heart sounds on
      short, unsegmented recordings. APPROACH: PCG segments of 5 s duration from the
      PhysioNet/Computing in Cardiology Challenge database were analysed. Initially the
      5 s segment at the start of each recording (seg 1) was analysed. Segments were
      zero-mean but otherwise had no pre-processing or segmentation. Normalised
      spectral amplitude was determined by fast Fourier transform and wavelet entropy
      by wavelet analysis. For each of these a simple single feature threshold-based
      classifier was implemented and the frequency/scale and thresholds for optimum
      classification accuracy determined. The analysis was then repeated using
      relatively noise free 5 s segments (seg 2) of each recording. Spectral amplitude
      and wavelet entropy features were then combined in a classification tree. MAIN
      RESULTS: There were significant differences between normal and abnormal
      recordings for both wavelet entropy and spectral amplitude across scales and
      frequency. In the wavelet domain the differences between groups were greatest at
      highest frequencies (wavelet scale 1, pseudo frequency 1 kHz) whereas in the
      frequency domain the differences were greatest at low frequencies (12 Hz).
      Abnormal recordings had significantly reduced high frequency wavelet entropy:
      (Median (interquartile range)) 6.63 (2.42) versus 8.36 (1.91), p  <  0.0001,
      suggesting the presence of discrete high frequency components in these
      recordings. Abnormal recordings exhibited significantly greater low frequency (12
      Hz) spectral amplitude: 0.24 (0.22) versus 0.09 (0.15), p  <  0.0001.
      Classification accuracy (mean of specificity and sensitivity) was greatest for
      wavelet entropy: 76% (specificity 54%, sensitivity 98%) versus 70% (specificity
      65%, sensitivity 75%) and was further improved by selecting the lowest noise
      segment (seg 2): 80% (specificity 65%, sensitivity 94%) versus 71% (specificity
      63%, sensitivity 79%). Classification tree with combined features gave accuracy
      79% (specificity 80%, sensitivity 77%). SIGNIFICANCE: The feasibility of accurate
      classification without segmentation of the characteristic heart sounds has been
      demonstrated. Classification accuracy is comparable to other algorithms but
      achieved without the complexity of segmentation.

PMID- 28489020
TI  - Correspondence between visual and electrical input filters of ON and OFF mouse
      retinal ganglion cells.
AB  - OBJECTIVE: Over the past two decades retinal prostheses have made major strides
      in restoring functional vision to patients blinded by diseases such as retinitis
      pigmentosa. Presently, implants use single pulses to activate the retina. Though
      this stimulation paradigm has proved beneficial to patients, an unresolved
      problem is the inability to selectively stimulate the on and off visual pathways.
      To this end our goal was to test, using white noise, voltage-controlled,
      cathodic, monophasic pulse stimulation, whether different retinal ganglion cell
      (RGC) types in the wild type retina have different electrical input filters. This
      is an important precursor to addressing pathway-selective stimulation. APPROACH:
      Using full-field visual flash and electrical and visual Gaussian noise
      stimulation, combined with the technique of spike-triggered averaging (STA), we
      calculate the electrical and visual input filters for different types of RGCs
      (classified as on, off or on-off based on their response to the flash stimuli).
      MAIN RESULTS: Examining the STAs, we found that the spiking activity of on cells
      during electrical stimulation correlates with a decrease in the voltage magnitude
      preceding a spike, while the spiking activity of off cells correlates with an
      increase in the voltage preceding a spike. No electrical preference was found for
      on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower
      electrical STA deflections with shorter latencies in rd10. SIGNIFICANCE: This
      study is the first comparison of visual cell types and their corresponding
      temporal electrical input filters in the retina. The altered input filters in
      degenerated rd10 retinas are consistent with photoreceptor stimulation underlying
      visual type-specific electrical STA shapes in wild type retina. It is therefore
      conceivable that existing implants could target partially degenerated
      photoreceptors that have only lost their outer segments, but not somas, to
      selectively activate the on and off visual pathways.

PMID- 28489022
TI  - Lactic Fermentation as an Efficient Tool to Enhance the Antioxidant Activity of
      Tropical Fruit Juices and Teas.
AB  - Tropical fruits like pineapple, papaya, mango, and beverages such as green or
      black teas, represent an underestimated source of antioxidants that could exert
      health-promoting properties. Most food processing technologies applied to fruit
      beverages or teas result in an impairment of inherent nutritional properties.
      Conversely, we hypothesise that lactic acid fermentation may constitute a
      promising route to maintain and even improve the nutritional qualities of
      processed fruits. Using specific growth media, lactic acid bacteria were selected
      from the fruit phyllosphere diversity and fruit juice, with the latter undergoing
      acidification kinetics analyses and characterised for exopolysaccharide
      production. Strains able to ferment tropical fruit juices or teas into pleasant
      beverages, within a short time, were of particular interest. Strains Weissella
      cibaria 64 and Leuconostoc mesenteroides 12b, able to increase antioxidant
      activity, were specifically studied as potential starters for lactic fermented
      pineapple juice.

PMID- 28489021
TI  - Calcium Dynamics Mediated by the Endoplasmic/Sarcoplasmic Reticulum and Related
      Diseases.
AB  - The flow of intracellular calcium (Ca2+) is critical for the activation and
      regulation of important biological events that are required in living organisms.
      As the major Ca2+ repositories inside the cell, the endoplasmic reticulum (ER)
      and the sarcoplasmic reticulum (SR) of muscle cells are central in maintaining
      and amplifying the intracellular Ca2+ signal. The morphology of these organelles,
      along with the distribution of key calcium-binding proteins (CaBPs), regulatory
      proteins, pumps, and receptors fundamentally impact the local and global
      differences in Ca2+ release kinetics. In this review, we will discuss the
      structural and morphological differences between the ER and SR and how they
      influence localized Ca2+ release, related diseases, and the need for targeted
      genetically encoded calcium indicators (GECIs) to study these events.

PMID- 28489023
TI  - High Sensitivity Determination of TNF-alpha for Early Diagnosis of Neonatal
      Infections with a Novel and Reusable Electrochemical Sensor.
AB  - Early diagnosis is vital for the reduction of mortality caused by neonatal
      infections. Since TNF-alpha can be used as a marker for the early diagnosis, the
      detection of TNF-alpha with high sensitivity and specificity has great clinical
      significance. Herein, a highly sensitive and reusable electrochemical sensor was
      fabricated. Due to the high specificity of aptamers, TNF-alpha could be
      accurately detected from five similar cytokines, even from serum samples. In
      addition, Au nanoparticles (AuNPs) with a high surface area were able to combine
      a large number of doxorubicin hydrochloride (DOXh), which made the sensor have a
      high sensitivity. The sensor had a good linear relationship with TNF-alpha
      concentration in the range from 1 to 1 * 104 pg/mL and the lowest detection limit
      is 0.7 pg/mL. More important was that the sensor could be reused 6 times by a
      crafty use of chain replacement reaction. Meanwhile, the detection time and cost
      were greatly reduced. Thus, we believe that these advantages of higher
      specificity and sensitivity, lower cost, and shorter detection time will provide
      a stronger potential for early diagnosis of neonatal infections in clinical
      applications.

PMID- 28489025
TI  - Plasticizing Effects of Polyamines in Protein-Based Films.
AB  - Zeta potential and nanoparticle size were determined on film forming solutions of
      native and heat-denatured proteins of bitter vetch as a function of pH and of
      different concentrations of the polyamines spermidine and spermine, both in the
      absence and presence of the plasticizer glycerol. Our results showed that both
      polyamines decreased the negative zeta potential of all samples under pH 8.0 as a
      consequence of their ionic interaction with proteins. At the same time, they
      enhanced the dimension of nanoparticles under pH 8.0 as a result of
      macromolecular aggregations. By using native protein solutions, handleable films
      were obtained only from samples containing either a minimum of 33 mM glycerol or
      4 mM spermidine, or both compounds together at lower glycerol concentrations.
      However, 2 mM spermidine was sufficient to obtain handleable film by using heat
      treated samples without glycerol. Conversely, brittle materials were obtained by
      spermine alone, thus indicating that only spermidine was able to act as an ionic
      plasticizer. Lastly, both polyamines, mainly spermine, were found able to act as
      "glycerol-like" plasticizers at concentrations higher than 5 mM under
      experimental conditions at which their amino groups are undissociated. Our
      findings open new perspectives in obtaining protein-based films by using
      aliphatic polycations as components.

PMID- 28489024
TI  - The Role of the N-Terminal Domains of Bacterial Initiator DnaA in the Assembly
      and Regulation of the Bacterial Replication Initiation Complex.
AB  - The primary role of the bacterial protein DnaA is to initiate chromosomal
      replication. The DnaA protein binds to DNA at the origin of chromosomal
      replication (oriC) and assembles into a filament that unwinds double-stranded
      DNA. Through interaction with various other proteins, DnaA also controls the
      frequency and/or timing of chromosomal replication at the initiation step.
      Escherichia coli DnaA also recruits DnaB helicase, which is present in unwound
      single-stranded DNA and in turn recruits other protein machinery for replication.
      Additionally, DnaA regulates the expression of certain genes in E. coli and a few
      other species. Acting as a multifunctional factor, DnaA is composed of four
      domains that have distinct, mutually dependent roles. For example, C-terminal
      domain IV interacts with double-stranded DnaA boxes. Domain III drives ATP
      dependent oligomerization, allowing the protein to form a filament that unwinds
      DNA and subsequently binds to and stabilizes single-stranded DNA in the initial
      replication bubble; this domain also interacts with multiple proteins that
      control oligomerization. Domain II constitutes a flexible linker between C
      terminal domains III-IV and N-terminal domain I, which mediates intermolecular
      interactions between DnaA and binds to other proteins that affect DnaA activity
      and/or formation of the initiation complex. Of these four domains, the role of
      the N-terminus (domains I-II) in the assembly of the initiation complex is the
      least understood and appears to be the most species-dependent region of the
      protein. Thus, in this review, we focus on the function of the N-terminus of DnaA
      in orisome formation and the regulation of its activity in the initiation complex
      in different bacteria.

PMID- 28489026
TI  - Redox Regulation of the Tumor Suppressor PTEN by Hydrogen Peroxide and Tert-Butyl
      Hydroperoxide.
AB  - Organic peroxides and hydroperoxides are skin tumor promoters. Free radical
      derivatives from these compounds are presumed to be the prominent mediators of
      tumor promotion. However, the molecular targets of these species are unknown.
      Phosphatase and tensin homologs deleted on chromosome 10 (PTEN) are tumor
      suppressors that play important roles in cell growth, proliferation, and cell
      survival by negative regulation of phosphoinositol-3-kinase/protein kinase B
      signaling. PTEN is reversibly oxidized in various cells by exogenous and
      endogenous hydrogen peroxide. Oxidized PTEN is converted back to the reduced form
      by cellular reducing agents, predominantly by the thioredoxin (Trx) system. Here,
      the role of tert-butyl hydroperoxide (t-BHP) in redox regulation of PTEN was
      analyzed by using cell-based and in vitro assays. Exposure to t-BHP led to
      oxidation of recombinant PTEN. In contrast to H2O2, PTEN oxidation by t-BHP was
      irreversible in HeLa cells. However, oxidized PTEN was reduced by exogenous Trx
      system. Taken together, these results indicate that t-BHP induces PTEN oxidation
      and inhibits Trx system, which results in irreversible PTEN oxidation in HeLa
      cells. Collectively, these results suggest a novel mechanism of t-BHP in the
      promotion of tumorigenesis.

PMID- 28489027
TI  - Direct Analyses of Secondary Metabolites by Mass Spectrometry Imaging (MSI) from
      Sunflower (Helianthus annuus L.) Trichomes.
AB  - Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate
      glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal
      different chemical compositions and locations in different plant tissues. With
      matrix-assisted laser desorption/ionization (MALDI) and laser
      desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient
      methods were developed to analyze the tissue distribution of secondary
      metabolites (flavonoids and sesquiterpenes) and proteins inside of trichomes.
      Herein, we analyzed sesquiterpene lactones, present in CGT, from leaf transversal
      sections using the matrix 2,5-dihydroxybenzoic acid (DHB) and alpha-cyano-4
      hydroxycinnamic acid (CHCA) (mixture 1:1) with sodium ions added to increase the
      ionization in positive ion mode. The results observed for sesquiterpenes and
      polymethoxylated flavones from LGT were similar. However, upon desiccation, LGT
      changed their shape in the ionization source, complicating analyses by MSI mainly
      after matrix application. An alternative method could be applied to LGT regions
      by employing LDI (without matrix) in negative ion mode. The polymethoxylated
      flavones were easily ionized by LDI, producing images with higher resolution, but
      the sesquiterpenes were not observed in spectra. Thus, the application and
      viability of MALDI imaging for the analyses of protein and secondary metabolites
      inside trichomes were confirmed, highlighting the importance of optimization
      parameters.

PMID- 28489028
TI  - Synthesis and Characterization of Nano-Conducting Copolymer Composites: Efficient
      Sorbents for Organic Pollutants.
AB  - Nano-conducting copolymers of aniline (ANI) and pyrrole (Py) with silica of
      different starting monomer ratios are prepared by oxidative chemical
      polymerization. X-ray diffraction (XRD) data showed that polyaniline (PANI) is
      the predominant phase in copolymer composites with a higher starting ANI monomer
      ratio while polypyrrole (PPy) is the major phase for other prepared samples.
      Transmission and scanning electron microscope images ascertained XRD results
      where hexagonal-shaped particles are assigned to PANI/SiO2 and poly(9ANI-co
      1Py)/SiO2 samples; the cauliflower morphology can be observed for PPy/SiO2,
      poly(1ANI-co-9Py)/SiO2, poly(1ANI-co-2Py)/SiO2, and poly(1ANI-co-1Py)/SiO2
      samples. One-dimensional nano-fibers can be obtained by using a starting monomer
      ratio of 2ANI:1Py during synthesis. Thermal analysis showed that copolymerization
      increases the thermal stability as compared with PANI/SiO2 and PPy/SiO2
      composites. All prepared samples were applied as sorbents for Congo red dye from
      aqueous solutions. It was found that the sorption capacity value was affected by
      the starting monomer ratio; poly(2ANI-co-1Py)/SiO2 has the highest sorption
      capacity; the qm value is 142.9 mg g-1 due to its highly-stabilized nano
      structure.

PMID- 28489029
TI  - Comparative Analysis of the Major Chemical Constituents in Salvia miltiorrhiza
      Roots, Stems, Leaves and Flowers during Different Growth Periods by UPLC-TQ-MS/MS
      and HPLC-ELSD Methods.
AB  - Salvia miltiorrhiza is a traditional Chinese herbal medicine containing multiple
      components that contribute to its notable bioactivities. This article
      investigated the distribution and dynamic changes of chemical constituents in
      various parts of S. miltiorrhiza from different growth periods. An ultra-high
      performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-TQ
      MS/MS) and high-performance liquid chromatography coupled with evaporative light
      scattering detector (HPLC-ELSD) methods were developed for accurate determination
      of 24 compounds (including phenolic acids, flavonoids, triterpenes, and
      saccharides) in S. miltiorrhiza. The established methods were validated with good
      linearity, precision, repeatability, stability, and recovery. Results indicated
      that there were category and quantity discrepancies in different parts of the
      plant, for the roots mainly contained salvianolic acids and tanshinones, and most
      of the saccharides are stachyose. In the aerial parts, salvianolic acids,
      flavonoids, and triterpenes, except the tanshinones, were detected, and the
      saccharides were mainly monosaccharides. Dynamic accumulation analysis suggested
      the proper harvest time for S. miltiorrhiza Bunge was the seedling stage in
      spring, and for the aerial parts was July to August. This study provided valuable
      information for the development and utilization value of the aerial parts of S.
      miltiorrhiza and was useful for determining the optimal harvest time of the
      plant.

PMID- 28489031
TI  - Effect of Cold Storage and Reheating of Parboiled Rice on Postprandial Glycaemic
      Response, Satiety, Palatability and Chewed Particle Size Distribution.
AB  - Background: Globally, hot cooked refined rice is consumed in large quantities and
      is a major contributor to dietary glycaemic load. This study aimed to compare the
      glycaemic potency of hot- and cold-stored parboiled rice to widely available
      medium-grain white rice. Method: Twenty-eight healthy volunteers participated in
      a three-treatment experiment where postprandial blood glucose was measured over
      120 min after consumption of 140 g of rice. The three rice samples were freshly
      cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice
      stored overnight at 4  degrees C. All rice was served warm at 65  degrees C.
      Chewing time was recorded. Results: incremental area under the curve (iAUC) of
      the control rice, freshly cooked medium-grain white rice, was the highest: 1.7
      fold higher (1.2, 2.6) than reheated parboiled rice (p < 0.001) and 1.5-fold
      higher (1.0, 2.2) than freshly cooked parboiled rice (p = 0.001). No significant
      difference in postprandial glycaemic response was observed between freshly cooked
      and reheated parboiled rice samples (p = 0.445). Chewing time for 10 g cold
      stored parboiled rice was 6 s (25%) longer and was considered more palatable,
      visually appealing and better tasting than freshly cooked medium-grain (all p <
      0.05). Conclusions: For regular consumers of rice, reheating cooked rice after
      cold storage would lower the dietary glycaemic load and, in the long term, may
      reduce the risk for type 2 and gestational diabetes. More trials are needed to
      identify the significance.

PMID- 28489030
TI  - A Review of Recruitment, Adherence and Drop-Out Rates in Omega-3 Polyunsaturated
      Fatty Acid Supplementation Trials in Children and Adolescents.
AB  - INTRODUCTION: The influence of n-3 long-chain polyunsaturated fatty acids (n-3
      LCPUFA) supplementation on health outcomes has been studied extensively with
      randomized controlled trials (RCT). In many research fields, difficulties with
      recruitment, adherence and high drop-out rates have been reported. However, what
      is unknown is how common these problems are in n-3 LCPUFA supplementation studies
      in children and adolescents. Therefore, this paper will review n-3 LCPUFA
      supplementation studies in children and adolescents with regard to recruitment,
      adherence and drop-out rates. METHODS: The Web of Science, PubMed and Ovid
      databases were searched for papers reporting on RCT supplementing children and
      adolescents (2-18 years) with a form of n-3 LCPUFA (or placebo) for at least four
      weeks. As a proxy for abiding to CONSORT guidelines, we noted whether manuscripts
      provided a flow-chart and provided dates defining the period of recruitment and
      follow-up. RESULTS: Ninety manuscripts (reporting on 75 studies) met the
      inclusion criteria. The majority of the studies did not abide by the CONSORT
      guidelines: 55% did not provide a flow-chart, while 70% did not provide dates.
      The majority of studies provided minimal details about the recruitment process.
      Only 25 of the 75 studies reported an adherence rate which was on average 85%.
      Sixty-five of the 75 studies included drop-out rates which were on average 17%.
      CONCLUSION: Less than half of the included studies abided by the CONSORT
      guidelines (45% included a flow chart, while 30% reported dates). Problems with
      recruitment and drop-out seem to be common in n-3 LCPUFA supplementation trials
      in children and adolescents. However, reporting about recruitment, adherence and
      dropout rates was very heterogeneous and minimal in the included studies. Some
      techniques to improve recruitment, adherence and dropout rates were identified
      from the literature, however these techniques may need to be tailored to n-3
      LCPUFA supplementation studies in children and adolescents.

PMID- 28489032
TI  - Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D
      Concentrations in Critical and Severe Hand, Foot and Mouth Disease.
AB  - OBJECTIVE: To examine the association of serum 25-hydroxyvitamin D [25(OH)D]
      concentrations with critical and severe hand, foot and mouth disease (HFMD) and
      assess the clinical significance and prognostic effect of 25(OH)D concentrations
      in children with HFMD. METHODS: This is a prospective observational study. The
      138 children with HFMD were divided into common (49 cases), severe (52 cases),
      and critical (37 cases) HFMD groups. Another 59 healthy children undergoing
      outpatient medical examinations during the same period were chosen as the control
      group. Serum 25(OH)D concentrations were measured in all the subjects, and each
      group was subdivided by serum 25(OH)D concentration into 25(OH)D normal (>=30
      ng/mL); insufficiency (20-29.9 ng/mL), and deficiency (<20 ng/mL) groups. The
      pediatric critical illness score (PCIS) was recorded for the critical and severe
      HFMD group upon admission to the pediatric intensive care unit (PICU). Children
      with critical and severe HFMD were also monitored for blood lactate (LAC), serum
      calcium ions (Ca++), D-dimer (DD), lactate dehydrogenase (LDH), and creatine
      kinase-MB (CK-MB) levels; the incidences of brainstem encephalitis, neurogenic
      pulmonary edema, and circulatory failure; and the 14-day mortality rate. RESULTS:
      Serum 25(OH)D concentrations were generally low in all groups. The critical HFMD
      group showed a significantly lower serum 25(OH)D mean concentration (20.0 +/- 8.4
      ng/mL) and a higher proportion of deficiency (18%) compared with the control
      group (28.1 +/- 6.6 ng/mL, 8%), common (29.5 +/- 8.1 ng/mL, 10%) and severe (31.9
      +/- 9.7 ng/mL, 8%) HFMD groups (p < 0.05). In the critical and severe HFMD
      groups, the 25(OH)D deficiency group had lower PCISs than the 25(OH)D normal and
      insufficiency groups (p < 0.05); and had higher values than the latter two groups
      for LAC, LDH, CK-MB and DD; and the incidences of brainstem encephalitis,
      neurogenic pulmonary edema, circulatory failure, and mortality (p < 0.05). The
      death group showed significantly lower serum 25(OH)D concentrations and PCISs
      than the survival group (p < 0.05) and had higher LAC, LDH, CK-MB and DD levels
      and higher incidences of brainstem encephalitis, neurogenic pulmonary edema, and
      circulatory failure (p < 0.05). Logistic regression analysis revealed that the
      serum 25(OH)D concentration was an independent factor that influenced mortality
      in children with critical and severe HFMD. CONCLUSIONS: In this study, we find
      the serum 25(OH)D concentrations are substantially reduced in children with
      critical and severe HFMD and are associated with the severity of HFMD. The serum
      25(OH)D concentrations may have clinical value for determining the progression of
      critical HFMD and predicting the risk of death. Further evidence is needed before
      it can be stated that 25(OH)D concentrations have clinical value in HMFD
      diagnosis.

PMID- 28489033
TI  - Efficient Fluorescence Resonance Energy Transfer between Quantum Dots and Gold
      Nanoparticles Based on Porous Silicon Photonic Crystal for DNA Detection.
AB  - A novel assembled biosensor was prepared for detecting 16S rRNA, a small-size
      persistent specific for Actinobacteria. The mechanism of the porous silicon (PS)
      photonic crystal biosensor is based on the fluorescence resonance energy transfer
      (FRET) between quantum dots (QDs) and gold nanoparticles (AuNPs) through DNA
      hybridization, where QDs act as an emission donor and AuNPs serve as a
      fluorescence quencher. Results showed that the photoluminescence (PL) intensity
      of PS photonic crystal was drastically increased when the QDs-conjugated probe
      DNA was adhered to the PS layer by surface modification using a standard cross
      link chemistry method. The PL intensity of QDs was decreased when the addition of
      AuNPs-conjugated complementary 16S rRNA was dropped onto QDs-conjugated PS. Based
      on the analysis of different target DNA concentration, it was found that the
      decrease of the PL intensity showed a good linear relationship with complementary
      DNA concentration in a range from 0.25 to 10 MUM, and the detection limit was
      328.7 nM. Such an optical FRET biosensor functions on PS-based photonic crystal
      for DNA detection that differs from the traditional FRET, which is used only in
      liquid. This method will benefit the development of a new optical FRET label-free
      biosensor on Si substrate and has great potential in biochips based on integrated
      optical devices.

PMID- 28489034
TI  - The Prevalence of Vitamin D Insufficiency and Deficiency and Their Relationship
      with Bone Mineral Density and Fracture Risk in Adults Receiving Long-Term Home
      Parenteral Nutrition.
AB  - It has been demonstrated that low bone mass and vitamin D deficiency occur in
      adult patients receiving home parenteral nutrition (HPN). The aim of this study
      is to determine the prevalence of vitamin D insufficiency and deficiency and its
      relationship with bone mineral density (BMD) and fracture risk in long-term HPN
      patients. Methods: A retrospective chart review of all 186 patients in the HPN
      registry followed by the Northern Alberta Home Parenteral Nutrition Program
      receiving HPN therapy >6 months with a 25 (OH) D level and BMD reported were
      studied. Results: The mean age at the initiation of HPN was 53.8 (20-79) years
      and 23 (37%) were male. The mean HPN duration was 56 (6-323) months and the most
      common diagnosis was short bowel syndrome. Based on a total of 186 patients, 62
      patients were categorized based on serum vitamin D status as follows: 1 (24.2%)
      sufficient, 31 (50%) insufficient and 16 (25.8%) deficient. Despite an average of
      1891 IU/day orally and 181 IU/day intravenously vitamin D, the mean vitamin D
      level was 25.6 ng/mL (insufficiency) and 26.2 +/- 11.9 ng/mL in patients with the
      highest 10-year fracture risk. Conclusion: Suboptimal vitamin D levels are common
      among patients on long-term HPN despite nutrient intake that should meet
      requirements.

PMID- 28489035
TI  - Development of Conductivity Sensors for Multi-Phase Flow Local Measurements at
      the Polytechnic University of Valencia (UPV) and University Jaume I of Castellon
      (UJI).
AB  - This paper describes all the procedures and methods currently used at UPV
      (Universitat Politecnica de Valencia) and UJI (University Jaume I) for the
      development and use of sensors for multi-phase flow analysis in vertical pipes.
      This paper also describes the methods that we use to obtain the values of the two
      phase flow magnitudes from the sensor signals and the validation and cross
      verification methods developed to check the consistency of the results obtained
      for these magnitudes with the sensors. First, we provide information about the
      procedures used to build the multi-sensor conductivity probes and some of the
      tests performed with different materials to avoid sensor degradation issues. In
      addition, we provide information about the characteristics of the electric
      circuits that feed the sensors. Then the data acquisition of the conductivity
      probe, the signal conditioning and the data processing including the device that
      have been designed to automatize all the measurement process of moving the
      sensors inside the channels by means of stepper electric motors controlled by
      computer are shown in operation. Then, we explain the methods used for bubble
      identification and categorization. Finally, we describe the methodology used to
      obtain the two-phase flow information from the sensor signals. This includes the
      following items: void fraction, gas velocity, Sauter mean diameter and
      interfacial area concentration. The last part of this paper is devoted to the
      conductance probes developed for the annular flow analysis, which includes the
      analysis of the interfacial waves produced in annular flow and that requires a
      different type of sensor.

PMID- 28489036
TI  - GryphSens: A Smartphone-Based Portable Diagnostic Reader for the Rapid Detection
      of Progesterone in Milk.
AB  - Enzyme-linked immunosorbent assay (ELISA) is a popular assay technique for the
      detection and quantification of various biological substances due its high
      sensitivity and specificity. More often, it requires large and expensive
      laboratory instruments, which makes it difficult to conduct when the tests must
      be performed quickly at the point-of-care (POC). To increase portability and ease
      of use, we propose a portable diagnostic system based on a Raspberry Pi imaging
      sensor for the rapid detection of progesterone in milk samples. We designed,
      assembled, and tested a standalone portable diagnostic reader and validated it
      for progesterone detection against a standard ELISA assay using a commercial
      plate reader. The portable POC device yielded consistent results, regardless of
      differences in the cameras and flashlights between various smartphone devices. An
      Android application was built to provide front-end access to users, control the
      diagnostic reader, and display and store the progesterone measurement on the
      smartphone. The diagnostic reader takes images of the samples, reads the pixel
      values, processes the results, and presents the results on the handheld device.
      The proposed POC reader can perform to superior levels of performance as a plate
      reader, while adding the desirable qualities of portability and ease of use.

PMID- 28489037
TI  - Color-Coded Front-of-Pack Nutrition Labels-An Option for US Packaged Foods?
AB  - The implementation of a standardized front-of-pack-labelling (FoPL) scheme would
      likely be a useful tool for many consumers trying to improve the healthfulness of
      their diets. Our objective was to examine what the traffic light labelling scheme
      would look like if implemented in the US. Data were extracted from Label
      Insight's Open Access branded food database in 2017. Nutrient levels and the
      proportion of products classified as "Red" (High), "Amber" (Medium) or "Green"
      (Low) in total fat, saturated fat, total sugar and sodium for food and beverage
      items were examined. The proportion of products in each category that had each
      possible combination of traffic light colors, and met the aggregate score for
      "healthy" was examined. Out of 175,198 products, >50% of all US packaged foods
      received a "Red" rating for total sugar and sodium. "Confectionery" had the
      highest mean total sugar (51.9 g/100 g) and "Meat and meat alternatives" the
      highest mean sodium (781 mg/100 g). The most common traffic light label
      combination was "Red" for total fat, saturated fat and sodium and "Green" for
      sugar. Only 30.1% of products were considered "healthy". A wide variety (n = 80)
      of traffic light color combinations were observed. A color coded traffic light
      scheme appears to be an option for implementation across the US packaged food
      supply to support consumers in making healthier food choices.

PMID- 28489038
TI  - Transparent Nanotubular TiO2 Photoanodes Grown Directly on FTO Substrates.
AB  - This work describes the preparation of transparent TiO2 nanotube (TNT) arrays on
      fluorine-doped tin oxide (FTO) substrates. An optimized electrolyte composition
      (0.2 mol dm-3 NH4F and 4 mol dm-3 H2O in ethylene glycol) was used for the
      anodization of Ti films with different thicknesses (from 100 to 1300 nm)
      sputtered on the FTO glass substrates. For Ti thicknesses 600 nm and higher,
      anodization resulted in the formation of TNT arrays with an outer nanotube
      diameter around 180 nm and a wall thickness around 45 nm, while for anodized Ti
      thicknesses of 100 nm, the produced nanotubes were not well defined. The
      transmittance in the visible region (lambda = 500 nm) varied from 90% for the
      thinnest TNT array to 65% for the thickest TNT array. For the fabrication of
      transparent TNT arrays by anodization, the optimal Ti thickness on FTO was around
      1000 nm. Such fabricated TNT arrays with a length of 2500 nm exhibit stable
      photocurrent densities in aqueous electrolytes (~300 uA cm-2 at potential 0.5 V
      vs. Ag/AgCl). The stability of the photocurrent response and a sufficient
      transparency (>=65%) enables the use of transparent TNT arrays in
      photoelectrochemical applications when the illumination from the
      support/semiconductor interface is a necessary condition and the transmitted
      light can be used for another purpose (photocathode or photochemical reaction in
      the electrolyte).

PMID- 28489039
TI  - Third Generation Antivenomics: Pushing the Limits of the In Vitro Preclinical
      Assessment of Antivenoms.
AB  - Second generation antivenomics is a translational venomics approach designed to
      complement in vivo preclinical neutralization assays. It provides qualitative and
      quantitative information on the set of homologous and heterologous venom proteins
      presenting antivenom-recognized epitopes and those exhibiting impaired
      immunoreactivity. In a situation of worrying antivenom shortage in many tropical
      and sub-tropical regions with high snakebite mortality and morbidity rates, such
      knowledge has the potential to facilitate the optimal deployment of currently
      existing antivenoms and to aid in the rational design of novel broad specificity
      antidotes. The aim of the present work was to expand the analytical capability of
      the immunoaffinity second-generation antivenomics platform, endowing it with the
      ability to determine the maximal binding capacity of an antivenom toward the
      different toxins present in a venom, and to quantify the fraction of venom
      specific antibodies present in a given antivenom. The application of this new
      platform, termed third generation (3G) antivenomics, in the preclinical
      evaluation of antivenoms is illustrated in this paper for the case of antivenom
      EchiTAb-Plus-ICP(r) reactivity towards the toxins of homologous (B. arietans) and
      heterologous (N. melanoleuca) venoms.

PMID- 28489040
TI  - Nitride-Based Materials for Flexible MEMS Tactile and Flow Sensors in Robotics.
AB  - The response to different force load ranges and actuation at low energies is of
      considerable interest for applications of compliant and flexible devices
      undergoing large deformations. We present a review of technological platforms
      based on nitride materials (aluminum nitride and silicon nitride) for the
      microfabrication of a class of flexible micro-electro-mechanical systems. The
      approach exploits the material stress differences among the constituent layers of
      nitride-based (AlN/Mo, Si x N y /Si and AlN/polyimide) mechanical elements in
      order to create microstructures, such as upwardly-bent cantilever beams and bowed
      circular membranes. Piezoresistive properties of nichrome strain gauges and
      direct piezoelectric properties of aluminum nitride can be exploited for
      mechanical strain/stress detection. Applications in flow and tactile sensing for
      robotics are described.

PMID- 28489041
TI  - Effect of Gamma Irradiation on 2-Acetyl-1-pyrroline Content, GABA Content and
      Volatile Compounds of Germinated Rice (Thai Upland Rice).
AB  - Aroma intensity in rice is related to the level of 2-acetyl-1-pyrroline (2AP).
      The accumulation of 2AP in rice has been synthesized via l-proline metabolism by
      inactive betaine aldehyde dehydrogenase enzyme (BADH2), which activates 2AP
      accumulation. Meanwhile, active BADH2 inhibits 2AP accumulation but activates
      gamma-aminobutyric acid (GABA) accumulation. The improvement of 2AP content in
      rice has been reported under certain conditions, such as high salinity, water
      treatment, and reduction of high intensity solar exposure. In this study, we
      conducted the effects of gamma irradiation on 2AP content, GABA content and
      volatile compounds of germinated rice (Thai upland rice). Our results showed that
      the GABA content was highest when rice seeds germinated within a 24-h. The 2AP
      content of irradiated rice (germinated within a 24-h duration) was higher than
      non-irradiated rice for all gamma doses, particularly at 20 Gy, which showed a 23
      fold higher level of 2AP than non-irradiated rice. On the other hand, the
      reduction of the GABA content of irradiated rice was caused by an increase in the
      gamma dose. At 300 Gy, irradiated rice had a GABA content approximately 2.6-fold
      lower than non-irradiated rice. Moreover, we observed that a reduction of
      volatile compounds occurred when increasing gamma dose. However, some volatile
      compounds appeared in the irradiated rice at gamma doses of 60 Gy, 80 Gy, 100 Gy
      and 300 Gy. Furthermore, we observed that the level of Octanal, which is the
      compound most related to aroma intensity, of irradiated rice was stronger than
      that of non-irradiated rice. Our results demonstrate for the first time that 2AP
      and GABA contents are sensitive to gamma irradiation conditions. Moreover, the
      results indicate that the gamma irradiation technique can be used to improve the
      aroma intensity of rice.

PMID- 28489042
TI  - Spatial Analysis of Ambient PM2.5 Exposure and Bladder Cancer Mortality in
      Taiwan.
AB  - Fine particulate matter (PM2.5) is an air pollutant that is receiving intense
      regulatory attention in Taiwan. In previous studies, the effect of air pollution
      on bladder cancer has been explored. This study was conducted to elucidate the
      effect of atmospheric PM2.5 and other local risk factors on bladder cancer
      mortality based on available 13-year mortality data. Geographically weighted
      regression (GWR) was applied to estimate and interpret the spatial variability of
      the relationships between bladder cancer mortality and ambient PM2.5
      concentrations, and other variables were covariates used to adjust for the effect
      of PM2.5. After applying a GWR model, the concentration of ambient PM2.5 showed a
      positive correlation with bladder cancer mortality in males in northern Taiwan
      and females in most of the townships in Taiwan. This is the first time PM2.5 has
      been identified as a risk factor for bladder cancer based on the statistical
      evidence provided by GWR analysis.

PMID- 28489043
TI  - Underweight, Stunting and Wasting among Children in Kilimanjaro Region, Tanzania;
      a Population-Based Cross-Sectional Study.
AB  - This study assessed the prevalence and risk factors associated with underweight,
      stunting and wasting among children aged 0-24 months in six districts of
      Kilimanjaro region, northern Tanzania. A cross-sectional population-based study
      using a multistage, proportionate to size sampling was conducted from June 2010
      to March 2011. A structured questionnaire was used to collect sociodemographic,
      economic, feeding and child information. Anthropometric data were collected by
      trained field workers, and the data were used to assess child nutritional status.
      A total of 1870 children were enrolled in this study. The prevalence of children
      classified as underweight was 46.0%, stunting was 41.9%, and wasting was 24.7%.
      About 33% were both underweight and stunted, and 12% had all three conditions. In
      a multivariate logistic regression, child age, child being ill and birth weight
      were associated with all anthropometric indices. Child being breastfed was
      associated with being underweight and wasting. Mother's education was associated
      with being underweight and stunting. Fathers aged 35+ years, and living in the
      Hai district was associated with stunting, and being female was associated with
      wasting. The prevalence of child undernutrition is high in this region.
      Strategies that target each risk factor for child undernutrition may help to
      reduce the problem in the region.

PMID- 28489045
TI  - Discontinuity Detection in the Shield Metal Arc Welding Process.
AB  - This work proposes a new methodology for the detection of discontinuities in the
      weld bead applied in Shielded Metal Arc Welding (SMAW) processes. The detection
      system is based on two sensors-a microphone and piezoelectric-that acquire
      acoustic emissions generated during the welding. The feature vectors extracted
      from the sensor dataset are used to construct classifier models. The approaches
      based on Artificial Neural Network (ANN) and Support Vector Machine (SVM)
      classifiers are able to identify with a high accuracy the three proposed weld
      bead classes: desirable weld bead, shrinkage cavity and burn through
      discontinuities. Experimental results illustrate the system's high accuracy,
      greater than 90% for each class. A novel Hierarchical Support Vector Machine
      (HSVM) structure is proposed to make feasible the use of this system in
      industrial environments. This approach presented 96.6% overall accuracy. Given
      the simplicity of the equipment involved, this system can be applied in the metal
      transformation industries.

PMID- 28489044
TI  - What Type of Transitional Care Effectively Reduced Mortality and Improved ADL of
      Stroke Patients? A Meta-Analysis.
AB  - Stroke is a major cause of disability and mortality worldwide; yet; prior to this
      study; there had been no sufficient evidence to support the effectiveness of
      various transitional care interventions (TCI) on the disability and mortality of
      stroke survivors. This meta-analysis aimed to assess the effectiveness of TCI in
      reducing mortality and improving the activities of daily life (ADL) of stroke
      patients. PubMed; Web of Science; OVID; EMBASE; CINAHL; and Sino-Med were
      searched for articles published before November 2016. Thirty-one randomized
      controlled trials (RCTs) were identified in the study. This analysis showed that
      the total effect of TCI on reducing mortality was limited (Risk Ratio (RR) =
      0.86; 95% Confidence Interval (CI): 0.75-0.98); that only home-visiting programs
      could reduce mortality rates (RR = 0.34; 95% CI: 0.17-0.67) compared with usual
      care; and that the best intervention was led by a multidisciplinary team (MT) <=3
      months (RR = 0.19; 95% CI: 0.05-0.71). In addition; home-visiting programs also
      produced ADL benefit (RR = 0.56; 95% CI: 0.31-0.81). Overall; there was a
      statistically significant difference in improving patients' independence between
      TCI and usual care (RR = 1.12; 95% CI: 1.02-1.23). However; none of the
      interventions was effective when they were differentiated in the analysis. It is
      the conclusion of this study that home-visiting programs; especially those led by
      MTs; should receive the greatest consideration by healthcare systems or providers
      for implementing TCI to stroke survivors.

PMID- 28489046
TI  - Validity of Research-Grade Actigraphy Unit for Measuring Exercise Intensity.
AB  - This study was conducted in a free-living setting to investigate the measurement
      validity of a research-based actigraph for strolling and jogging, and to provide
      a reference for actual practice and research. Because inadequate physical
      activity (PA) or sedentary lifestyle has become the fourth leading risk factor
      for mortality worldwide, many countries have been vigorously promoting the
      concept of "active living", and the public has been investing greater effort into
      intensifying their PA. Although research-grade actigraphs have been widely
      applied to evaluate PA in routine environments, the measurement results may not
      accurately reflect the wearers' PA. Unlike most relevant research, which is
      conducted in well-controlled laboratory environments, the present study was
      implemented in the field to examine the sensitivity and convergent validity of
      the MicroMini Motionlogger(r) Actigraph during strolling and jogging. The
      following results were revealed: (1) Although the exercise movement speed while
      jogging was significantly faster than that while strolling, the actigraph
      readings showed no significant difference between strolling and jogging; (2) The
      actigraph readings were (significantly or nonsignificantly) negatively correlated
      with metabolic heat and nonsignificantly correlated with movement speeds. Hence,
      the actigraph validity for measuring PA intensity while strolling and jogging
      remains debatable.

PMID- 28489047
TI  - The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses.
AB  - Astroviruses are a diverse family of viruses that infect a wide range of
      mammalian and avian hosts. Here we describe the phylogenetic diversity and
      current classification methodology of astroviruses based on the ORF1b and ORF2
      genes, highlighting the propensity of astroviruses to undergo interspecies
      transmission and genetic recombination which greatly increase diversity and
      complicate attempts at a unified and comprehensive classification strategy.

PMID- 28489048
TI  - Multibehavioural Interventions with a Focus on Specific Energy Balance-Related
      Behaviours Can Affect Diet Quality in Preschoolers from Six European Countries:
      The ToyBox-Study.
AB  - The present study aimed to examine whether a multibehavioural intervention with a
      focus on specific energy balance-related behaviours can affect total diet quality
      and its four subcomponents in European preschoolers and to investigate if these
      intervention effects differed by socioeconomic status (SES). Parents/caregivers
      of 3.5 to 5.5 year-olds (n = 4968) recruited through kindergartens in six
      European countries within the ToyBox-study completed questionnaires on socio
      demographics and a food frequency questionnaire on their preschoolers' diet. To
      assess intervention effects and differences by SES, multilevel repeated measures
      analyses were conducted. In contrast to no significant difference in total diet
      quality, in both the intervention and control group, the dietary quality and
      dietary equilibrium increased, with a larger increase in the intervention group
      (mean difference quality: +3.4%; mean difference equilibrium: +0.9%) compared to
      the control group (quality: +1.5%; equilibrium: +0.2%). SES was not a significant
      moderator for intervention effects on total diet quality, nor for the four
      subcomponents. This study indicates that multibehavioural interventions with a
      focus on specific energy balance-related behaviours in preschoolers not only
      affect those targeted behaviours, but can also have more generalized effects. The
      ToyBox-intervention effects were similar for both lower and high SES
      preschoolers.

PMID- 28489049
TI  - Superparamagnetic Iron Oxide Nanoparticles-Complexed Cationic Amylose for In Vivo
      Magnetic Resonance Imaging Tracking of Transplanted Stem Cells in Stroke.
AB  - Cell-based therapy with mesenchymal stem cells (MSCs) is a promising strategy for
      acute ischemic stroke. In vivo tracking of therapeutic stem cells with magnetic
      resonance imaging (MRI) is imperative for better understanding cellular survival
      and migrational dynamics over time. In this study, we develop a novel
      biocompatible nanocomplex (ASP-SPIONs) based on cationic amylose, by introducing
      spermine and the image label, ultrasmall superparamagnetic iron oxide
      nanoparticles (SPIONs), to label MSCs. The capacity, efficiency, and cytotoxicity
      of the nanocomplex in transferring SPIONs into green fluorescence protein
      modified MSCs were tested; and the performance of in vivo MRI tracking of the
      transplanted cells in acute ischemic stroke was determined. The results
      demonstrated that the new class of SPIONs-complexed nanoparticles based on
      biodegradable amylose can serve as a highly effective and safe carrier to
      transfer magnetic label into stem cells. A reliable tracking of transplanted stem
      cells in stroke was achieved by MRI up to 6 weeks, with the desirable therapeutic
      benefit of stem cells on stroke retained. With the advantages of a relatively low
      SPIONs concentration and a short labeling period, the biocompatible complex of
      cationic amylose with SPIONs is highly translatable for clinical application. It
      holds great promise in efficient, rapid, and safe labeling of stem cells for
      subsequent cellular MRI tracking in regenerative medicine.

PMID- 28489051
TI  - Vehicle Counting and Moving Direction Identification Based on Small-Aperture
      Microphone Array.
AB  - The varying trend of a moving vehicle's angles provides much important
      intelligence for an unattended ground sensor (UGS) monitoring system. The present
      study investigates the capabilities of a small-aperture microphone array (SAMA)
      based system to identify the number and moving direction of vehicles travelling
      on a previously established route. In this paper, a SAMA-based acoustic
      monitoring system, including the system hardware architecture and algorithm
      mechanism, is designed as a single node sensor for the application of UGS. The
      algorithm is built on the varying trend of a vehicle's bearing angles around the
      closest point of approach (CPA). We demonstrate the effectiveness of our proposed
      method with our designed SAMA-based monitoring system in various experimental
      sites. The experimental results in harsh conditions validate the usefulness of
      our proposed UGS monitoring system.

PMID- 28489050
TI  - An In Vivo Magnetic Resonance Spectroscopy Study of the Effects of Caloric and
      Non-Caloric Sweeteners on Liver Lipid Metabolism in Rats.
AB  - We aimed to elucidate the effects of caloric and non-caloric sweeteners on liver
      lipid metabolism in rats using in vivo magnetic resonance spectroscopy (MRS) and
      to determine their roles in the development of liver steatosis. Wistar rats
      received normal chow and either normal drinking water, or solutions containing
      13% (w/v) glucose, 13% fructose, or 0.4% aspartame. After 7 weeks, in vivo
      hepatic dietary lipid uptake and de novo lipogenesis were assessed with proton
      observed, carbon-13-edited MRS combined with 13C-labeled lipids and 13C-labeled
      glucose, respectively. The molecular basis of alterations in hepatic liver
      metabolism was analyzed in detail ex vivo using immunoblotting and targeted
      quantitative proteomics. Both glucose and fructose feeding increased adiposity,
      but only fructose induced hepatic lipid accumulation. In vivo MRS showed that
      this was not caused by increased hepatic uptake of dietary lipids, but could be
      attributed to an increase in de novo lipogenesis. Stimulation of lipogenesis by
      fructose was confirmed by a strong upregulation of lipogenic enzymes, which was
      more potent than with glucose. The non-caloric sweetener aspartame did not
      significantly affect liver lipid content or metabolism. In conclusion, liquid
      fructose more severely affected liver lipid metabolism in rats than glucose,
      while aspartame had no effect.

PMID- 28489052
TI  - Crude Ecklonia cava Flake Extracts Attenuate Inflammation through the Regulation
      of TLR4 Signaling Pathway in LPS-Induced RAW264.7 Cells.
AB  - We investigated the beneficial effects of the crude Ecklonia cava flake (CEF),
      which is a residual product after polyphenol extraction from Ecklonia cava, on
      inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF
      extracts was obtained by a preparation process using water, hydrochloric acid or
      temperature. We observed that large-size (>19 kDa) CEF extract, which was
      extracted with water at 95  degrees C (CEF-W, 95  degrees C), suppressed the
      production of inflammatory cytokines by inhibiting its mRNA expression in LPS
      induced RAW264.7 cells. TLR4 signaling involvements were negatively regulated by
      CEF-W, 95  degrees C. CEF-W, 95  degrees C repressed the translocation of NF
      kappaB from cytoplasm into nucleus in LPS-induced RAW264.7 cells. CEF-W, 95 
      degrees C attenuated the phosphorylation of TBK1 and IRF3 by inhibiting the
      phosphorylation of ERK. Taken together, we demonstrated that large-size CEF-W, 95
      degrees C may act as a negative regulator of inflammation through the
      suppression of TLR4 signaling constituents in LPS-induced RAW264.7 cells.

PMID- 28489054
TI  - A Survey on an Energy-Efficient and Energy-Balanced Routing Protocol for Wireless
      Sensor Networks.
AB  - Wireless sensor networks (WSNs) form an important part of industrial application.
      There has been growing interest in the potential use of WSNs in applications such
      as environment monitoring, disaster management, health care monitoring,
      intelligence surveillance and defence reconnaissance. In these applications, the
      sensor nodes (SNs) are envisaged to be deployed in sizeable numbers in an
      outlying area, and it is quite difficult to replace these SNs after complete
      deployment in many scenarios. Therefore, as SNs are predominantly battery powered
      devices, the energy consumption of the nodes must be properly managed in order to
      prolong the network lifetime and functionality to a rational time. Different
      energy-efficient and energy-balanced routing protocols have been proposed in
      literature over the years. The energy-efficient routing protocols strive to
      increase the network lifetime by minimizing the energy consumption in each SN. On
      the other hand, the energy-balanced routing protocols protract the network
      lifetime by uniformly balancing the energy consumption among the nodes in the
      network. There have been various survey papers put forward by researchers to
      review the performance and classify the different energy-efficient routing
      protocols for WSNs. However, there seems to be no clear survey emphasizing the
      importance, concepts, and principles of load-balanced energy routing protocols
      for WSNs. In this paper, we provide a clear picture of both the energy-efficient
      and energy-balanced routing protocols for WSNs. More importantly, this paper
      presents an extensive survey of the different state-of-the-art energy-efficient
      and energy-balanced routing protocols. A taxonomy is introduced in this paper to
      classify the surveyed energy-efficient and energy-balanced routing protocols
      based on their proposed mode of communication towards the base station (BS). In
      addition, we classified these routing protocols based on the solution types or
      algorithms, and the input decision variables defined in the routing algorithm.
      The strengths and weaknesses of the choice of the decision variables used in the
      design of these energy-efficient and energy-balanced routing protocols are
      emphasised. Finally, we suggest possible research directions in order to optimize
      the energy consumption in sensor networks.

PMID- 28489053
TI  - Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract
      Pathogenesis in Ferrets (Mustela putorius furo).
AB  - Data from EV-D68-infected patients demonstrate that pathological changes in the
      lower respiratory tract are principally characterized by severe respiratory
      illness in children and acute flaccid myelitis. However, lack of a suitable
      animal model for EV-D68 infection has limited the study on the pathogenesis of
      this critical pathogen, and the development of a vaccine. Ferrets have been
      widely used to evaluate respiratory virus infections. In the current study, we
      used EV-D68-infected ferrets as a potential animal to identify impersonal
      indices, involving clinical features and histopathological changes in the upper
      and lower respiratory tract (URT and LRT). The research results demonstrate that
      the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the
      viral load detection in the feces, nasal, and respiratory tracts, the infection
      and shedding of EV-D68 in the ferret model was confirmed, and these results were
      supported by the EV-D68 VP1 immunofluorescence confocal imaging with alpha2,6
      linked sialic acid (SA) in lung tissues. Furthermore, we detected the
      inflammatory cytokine/chemokine expression level, which implied high expression
      levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs.
      These data indicate that systemic observation of responses following infection
      with EV-D68 in ferrets could be used as a model for EV-D68 infection and
      pathogenesis.

PMID- 28489055
TI  - Substrate Dependent Ad-Atom Migration on Graphene and the Impact on Electron-Beam
      Sculpting Functional Nanopores.
AB  - The use of atomically thin graphene for molecular sensing has attracted
      tremendous attention over the years and, in some instances, could displace the
      use of classical thin films. For nanopore sensing, graphene must be suspended
      over an aperture so that a single pore can be formed in the free-standing region.
      Nanopores are typically drilled using an electron beam (e-beam) which is tightly
      focused until a desired pore size is obtained. E-beam sculpting of graphene
      however is not just dependent on the ability to displace atoms but also the
      ability to hinder the migration of ad-atoms on the surface of graphene. Using
      relatively lower e-beam fluxes from a thermionic electron source, the C-atom
      knockout rate seems to be comparable to the rate of carbon ad-atom attraction and
      accumulation at the e-beam/graphene interface (i.e., Rknockout ~ Raccumulation).
      Working at this unique regime has allowed the study of carbon ad-atom migration
      as well as the influence of various substrate materials on e-beam sculpting of
      graphene. We also show that this information was pivotal to fabricating
      functional graphene nanopores for studying DNA with increased spatial resolution
      which is attributed to atomically thin membranes.

PMID- 28489056
TI  - MERITXELL: The Multifrequency Experimental Radiometer with Interference Tracking
      for Experiments over Land and Littoral-Instrument Description, Calibration and
      Performance.
AB  - MERITXELL is a ground-based multisensor instrument that includes a multiband dual
      polarization radiometer, a GNSS reflectometer, and several optical sensors. Its
      main goals are twofold: to test data fusion techniques, and to develop Radio
      Frequency Interference (RFI) detection, localization and mitigation techniques.
      The former is necessary to retrieve complementary data useful to develop
      geophysical models with improved accuracy, whereas the latter aims at solving one
      of the most important problems of microwave radiometry. This paper describes the
      hardware design, the instrument control architecture, the calibration of the
      radiometer, and several captures of RFI signals taken with MERITXELL in urban
      environment. The multiband radiometer has a dual linear polarization total-power
      radiometer topology, and it covers the L-, S-, C-, X-, K-, Ka-, and W-band. Its
      back-end stage is based on a spectrum analyzer structure which allows to perform
      real-time signal processing, while the rest of the sensors are controlled by a
      host computer where the off-line processing takes place. The calibration of the
      radiometer is performed using the hot-cold load procedure, together with the
      tipping curves technique in the case of the five upper frequency bands. Finally,
      some captures of RFI signals are shown for most of the radiometric bands under
      analysis, which evidence the problem of RFI in microwave radiometry, and the
      limitations they impose in external calibration.

PMID- 28489057
TI  - An Optimized Facile Procedure to Synthesize and Purify Allicin.
AB  - Allicin is a reactive sulfur species (RSS) and defence substance from garlic
      (Allium sativum L.). The compound is a broad-spectrum antibiotic that is also
      effective against multiple drug resistant (MDR) strains. A detailed protocol for
      allicin synthesis based on diallyl-disulfide (DADS) oxidation by H2O2 using
      acetic acid as a catalyst was published in 2001 by Lawson and Wang. Here we
      report on improvements to this basic method, clarify the mechanism of the
      reaction and show that it is zero-order with respect to DADS and first-order with
      respect to the concentration of H2O2. The progress of allicin synthesis and the
      reaction mechanism were analyzsd by high-performance liquid chromatography (HPLC)
      and the identity and purity of the products was verified with LC-MS and 1H-NMR.
      We were able to obtain allicin of high purity (>98%) and >91% yield, with
      standard equipment available in any reasonable biological laboratory. This
      protocol will enable researchers to prepare and work with easily and cheaply
      prepared allicin of high quality.

PMID- 28489058
TI  - The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action.
AB  - The neuroprotective role of phenolic acids from food has previously been reported
      by many authors. In this review, the role of phenolic acids in ameliorating
      depression, ischemia/reperfusion injury, neuroinflammation, apoptosis, glutamate
      induced toxicity, epilepsy, imbalance after traumatic brain injury,
      hyperinsulinemia-induced memory impairment, hearing and vision disturbances,
      Parkinson's disease, Huntington's disease, anti-amyotrophic lateral sclerosis,
      Chagas disease and other less distributed diseases is discussed. This review
      covers the in vitro, ex vivo and in vivo studies concerning the prevention and
      treatment of neurological disorders (on the biochemical and gene expression
      levels) by phenolic acids.

PMID- 28489059
TI  - The Impact of Diet Wheat Source on the Onset of Type 1 Diabetes Mellitus-Lessons
      Learned from the Non-Obese Diabetic (NOD) Mouse Model.
AB  - Nutrition, especially wheat consumption, is a major factor involved in the onset
      of type 1 diabetes (T1D) and other autoimmune diseases such as celiac. While
      modern wheat cultivars possess similar gliadin proteins associated with the onset
      of celiac disease and T1D, alternative dietary wheat sources from Israeli
      landraces and native ancestral species may be lacking the epitopes linked with
      T1D, potentially reducing the incidence of T1D. The Non-Obese Diabetic (NOD)
      mouse model was used to monitor the effects of dietary wheat sources on the onset
      and development of T1D. The effects of modern wheat flour were compared with
      those from either T. aestivum, T. turgidum spp. dicoccoides, or T. turgidum spp.
      dicoccum landraces or a non-wheat diet. Animals which received wheat from local
      landraces or ancestral species such as emmer displayed a lower incidence of T1D
      and related complications compared to animals fed a modern wheat variety. This
      study is the first report of the diabetogenic properties of various dietary wheat
      sources and suggests that alternative dietary wheat sources may lack T1D linked
      epitopes, thus reducing the incidence of T1D.

PMID- 28489060
TI  - The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and
      Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.
AB  - This study explored whether valproic acid (VPA, a histone deacetylase inhibitor)
      could radiosensitize osteosarcoma and primary-culture tumor cells, and determined
      the mechanism of VPA-induced radiosensitization. The working system included
      osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen
      (DMBA)-induced breast cancer in rats; and clonogenic survival,
      immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome
      aberrations, and comet assays were used in this study. It was found that VPA at
      the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the
      accumulation of more ionizing radiation (IR)-induced DNA double strand breaks,
      and increase the cell radiosensitivity. VPA-induced radiosensitivity was
      associated with the inhibition of DNA repair activity in the working systems. In
      addition, the chromosome aberrations including chromosome breaks, chromatid
      breaks, and radial structures significantly increased after the combination
      treatment of VPA and IR. Importantly, the results obtained by primary-culture
      cells from the tissue of chemical carcinogen-induced breast cancer in rats
      further confirmed our findings. The data in this study demonstrated that VPA at a
      safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells
      through suppressing DNA-double strand breaks repair function.

PMID- 28489062
TI  - Ultrasound Transmission Tomography for Detecting and Measuring Cylindrical
      Objects Embedded in Concrete.
AB  - This study explores the feasibility of using transmission tomographic images
      based on attenuation measures in transmission to detect and estimate the most
      common materials that are embedded in concrete, reinforcements and natural and
      artificial voids. A limited set of concrete specimens have been made in which
      cylindrical objects such as bars/tubes of steel, PVC and aluminium have been
      embedded to analyse the effect of size and material. The methodology and scope of
      this study is presented and numerical simulations are carried out to optimize the
      emitter-receiver configuration and to understand the complex physical propagation
      phenomena of ultrasonic signals that travel through concrete with embedded
      inclusions. Experimental tomographic images are obtained by using an ultrasonic
      tomographic system, which has the advantage of needing only two ultrasonic
      transducers. Both the software simulation tool and the tomographic inspection
      system are developed by the authors. The obtained results show that PVC tubes and
      steel bars of diameters higher than 19 mm and embedded in cylindrical specimens,
      can be detected and their sizes estimated using segmented tomographic images.

PMID- 28489061
TI  - Microbial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration
      by Blocking Nuclear Import of the Pre-Integration Complex.
AB  - While Highly Active Antiretroviral Therapy (HAART) has significantly decreased
      the mortality of human immunodeficiency virus (HIV)-infected patients, emerging
      drug resistance to approved HIV-1 integrase inhibitors highlights the need to
      develop new antivirals with novel mechanisms of action. In this study, we
      screened a library of microbial natural compounds from endophytic fungus
      Colletotrichum sp. and identified alternariol 5-O-methyl ether (AME) as a
      compound that inhibits HIV-1 pre-integration steps. Time-of addition analysis,
      quantitative real-time PCR, confocal microscopy, and WT viral replication assay
      were used to elucidate the mechanism. As opposed to the approved integrase
      inhibitor Raltegravir, AME reduced both the integrated viral DNA and the 2-long
      terminal repeat (2-LTR) circular DNA, which suggests that AME impairs the nuclear
      import of viral DNA. Further confocal microscopy studies showed that AME
      specifically blocks the nuclear import of HIV-1 integrase and pre-integration
      complex without any adverse effects on the importin alpha/beta and importin beta
      mediated nuclear import pathway in general. Importantly, AME inhibited
      Raltegravir-resistant HIV-1 strains and exhibited a broad anti-HIV-1 activity in
      diverse cell lines. These data collectively demonstrate the potential of AME for
      further development into a new HIV inhibitor, and suggest the utility of viral
      DNA nuclear import as a target for anti-HIV drug discovery.

PMID- 28489064
TI  - An Interference Mitigation Scheme of Device-to-Device Communications for Sensor
      Networks Underlying LTE-A.
AB  - Device-to-Device (D2D) communication technology has become a key factor in
      wireless sensor networks to form autonomous communication links among sensor
      nodes. Many research results for D2D have been presented to resolve different
      technical issues of D2D. Nevertheless, the previous works have not resolved the
      shortage of data rate and limited coverage of wireless sensor networks. Due to
      bandwidth shortages and limited communication coverage, 3rd Generation
      Partnership Project (3GPP) has introduced a new Device-to-Device (D2D)
      communication technique underlying cellular networks, which can improve spectral
      efficiencies by enabling the direct communication of devices in proximity without
      passing through enhanced-NodeB (eNB). However, to enable D2D communication in a
      cellular network presents a challenge with regard to radio resource management
      since D2D links reuse the uplink radio resources of cellular users and it can
      cause interference to the receiving channels of D2D user equipment (DUE). In this
      paper, a hybrid mechanism is proposed that uses Fractional Frequency Reuse (FFR)
      and Almost Blank Sub-frame (ABS) schemes to handle inter-cell interference caused
      by cellular user equipments (CUEs) to D2D receivers (DUE-Rxs), reusing the same
      resources at the cell edge area. In our case, DUE-Rxs are considered as victim
      nodes and CUEs as aggressor nodes, since our primary target is to minimize inter
      cell interference in order to increase the signal to interference and noise ratio
      (SINR) of the target DUE-Rx at the cell edge area. The numerical results show
      that the interference level of the target D2D receiver (DUE-Rx) decreases
      significantly compared to the conventional FFR at the cell edge. In addition, the
      system throughput of the proposed scheme can be increased up to 60% compared to
      the conventional FFR.

PMID- 28489063
TI  - African Swine Fever Virus: A Review.
AB  - African swine fever (ASF) is a highly contagious viral disease of swine which
      causes high mortality, approaching 100%, in domestic pigs. ASF is caused by a
      large, double stranded DNA virus, ASF virus (ASFV), which replicates
      predominantly in the cytoplasm of macrophages and is the only member of the
      Asfarviridae family, genus Asfivirus. The natural hosts of this virus include
      wild suids and arthropod vectors of the Ornithodoros genus. The infection of ASFV
      in its reservoir hosts is usually asymptomatic and develops a persistent
      infection. In contrast, infection of domestic pigs leads to a lethal hemorrhagic
      fever for which there is no effective vaccine. Identification of ASFV genes
      involved in virulence and the characterization of mechanisms used by the virus to
      evade the immune response of the host are recognized as critical steps in the
      development of a vaccine. Moreover, the interplay of the viral products with host
      pathways, which are relevant for virus replication, provides the basic
      information needed for the identification of potential targets for the
      development of intervention strategies against this disease.

PMID- 28489065
TI  - Sound Source Localization Using Non-Conformal Surface Sound Field Transformation
      Based on Spherical Harmonic Wave Decomposition.
AB  - Spherical microphone arrays have been paid increasing attention for their ability
      to locate a sound source with arbitrary incident angle in three-dimensional
      space. Low-frequency sound sources are usually located by using spherical near
      field acoustic holography. The reconstruction surface and holography surface are
      conformal surfaces in the conventional sound field transformation based on
      generalized Fourier transform. When the sound source is on the cylindrical
      surface, it is difficult to locate by using spherical surface conformal
      transform. The non-conformal sound field transformation by making a transfer
      matrix based on spherical harmonic wave decomposition is proposed in this paper,
      which can achieve the transformation of a spherical surface into a cylindrical
      surface by using spherical array data. The theoretical expressions of the
      proposed method are deduced, and the performance of the method is simulated.
      Moreover, the experiment of sound source localization by using a spherical array
      with randomly and uniformly distributed elements is carried out. Results show
      that the non-conformal surface sound field transformation from a spherical
      surface to a cylindrical surface is realized by using the proposed method. The
      localization deviation is around 0.01 m, and the resolution is around 0.3 m. The
      application of the spherical array is extended, and the localization ability of
      the spherical array is improved.

PMID- 28489066
TI  - Two Single Nucleotide Polymorphisms (rs2431697 and rs2910164) of miR-146a Are
      Associated with Risk of Coronary Artery Disease.
AB  - The coronary artery disease (CAD) is one of the most severe cardiovascular
      diseases. MicroRNA-146a (miR-146a) influences the pathology of cardiovascular
      diseases. Two single nucleotide polymorphisms (SNPs) of miR-146a (rs2431697 and
      rs2910164) have been reported to alter the function or expression of microRNA.
      The purpose of this study is to evaluate the association between miR-146a gene
      polymorphism and the risk of CAD in the Chinese population. A total of 353 CAD
      patients and 368 controls were recruited, and SNPs were analyzed by the matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and
      Sequenom MassARRAY system. The gene frequencies of rs2431697 and rs2910164 were
      significantly different between the two groups. The mutant type (T allele) of
      rs2431697 and wild type (C allele) of rs2910164 were more frequent in CAD
      patients. T allele carriers in rs2431697 had an increased CAD risk, while G
      allele of rs2910164 decreased the risk of CAD significantly. In conclusion, we
      found that the T allele of rs2431697 was a risk factor of CAD in the Chinese
      population. Meanwhile, we demonstrated that the G allele of rs2910164 decreased
      the susceptibility of CAD.

PMID- 28489067
TI  - A Study Protocol for Applying User Participation and Co-Learning-Lessons Learned
      from the eBalance Project.
AB  - The eBalance project is based on the idea that serious exergames-i.e., computer
      gaming systems with an interface that requires physical exertion to play-that are
      well adapted to users, can become a substantial part of a solution to recognized
      problems of insufficient engagement in fall-prevention exercise and the high
      levels of fall-related injuries among older people. This project is carried out
      as a collaboration between eight older people who have an interest in balance
      training and met the inclusion criteria of independence in personal activities of
      daily living, access to and basic knowledge of a computer, four staff working
      with the rehabilitation of older adults, and an interdisciplinary group of six
      research coordinators covering the areas of geriatric care and rehabilitation, as
      well as information technology and computer science. This paper describes the
      study protocol of the project's initial phase which aims to develop a working
      partnership with potential users of fall-prevention exergames, including its
      conceptual underpinnings. The qualitative methodology was inspired by an
      ethnographical approach implying combining methods that allowed the design to
      evolve through the study based on the participants' reflections. A participatory
      and appreciative action and reflection (PAAR) approach, accompanied by inquiries
      inspired by the Normalization Process Theory (NPT) was used in interactive
      workshops, including exergame testing, and between workshop activities. Data were
      collected through audio recordings, photos, and different types of written
      documentation. The findings provide a description of the methodology thus
      developed and applied. They display a methodology that can be useful for the
      design and development of care service and innovations for older persons where
      user participation is in focus.

PMID- 28489068
TI  - TNFalpha drives mitochondrial stress in POMC neurons in obesity.
AB  - Consuming a calorically dense diet stimulates microglial reactivity in the
      mediobasal hypothalamus (MBH) in association with decreased number of appetite
      curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC
      neuronal function is secondary to the microglial activation is unclear. Here we
      show that in hypercaloric diet-induced obese mice, persistently activated
      microglia in the MBH hypersecrete TNFalpha that in turn stimulate mitochondrial
      ATP production in POMC neurons, promoting mitochondrial fusion in their neurites,
      and increasing POMC neuronal firing rates and excitability. Specific disruption
      of the gene expressions of TNFalpha downstream signals TNFSF11A or NDUFAB1 in the
      MBH of diet-induced obese mice reverses mitochondrial elongation and reduces
      obesity. These data imply that in a hypercaloric environment, persistent
      elevation of microglial reactivity and consequent TNFalpha secretion induces
      mitochondrial stress in POMC neurons that contributes to the development of
      obesity.

PMID- 28489069
TI  - Histone variant H2A.J accumulates in senescent cells and promotes inflammatory
      gene expression.
AB  - The senescence of mammalian cells is characterized by a proliferative arrest in
      response to stress and the expression of an inflammatory phenotype. Here we show
      that histone H2A.J, a poorly studied H2A variant found only in mammals,
      accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J
      also accumulates in mice with aging in a tissue-specific manner and in human
      skin. Knock-down of H2A.J inhibits the expression of inflammatory genes that
      contribute to the senescent-associated secretory phenotype (SASP), and over
      expression of H2A.J increases the expression of some of these genes in
      proliferating cells. H2A.J accumulation may thus promote the signalling of
      senescent cells to the immune system, and it may contribute to chronic
      inflammation and the development of aging-associated diseases.

PMID- 28489070
TI  - Senescent tumor cells lead the collective invasion in thyroid cancer.
AB  - Cellular senescence has been perceived as a barrier against carcinogenesis.
      However, the senescence-associated secretory phenotype (SASP) of senescent cells
      can promote tumorigenesis. Here, we show senescent tumour cells are frequently
      present in the front region of collective invasion of papillary thyroid carcinoma
      (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in
      vitro invasion analysis, senescent tumour cells exhibit high invasion ability as
      compared with non-senescent tumour cells through SASP expression. Collective
      invasion in PTC is led by senescent tumour cells characterized by generation of a
      C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore,
      senescent cells increase the survival of cancer cells via CXCL12/CXCR4
      signalling. An orthotopic xenograft in vivo model also shows higher lymphatic
      vessels involvement in the group co-transplanted with senescent cells and cancer
      cells. These findings suggest that senescent cells are actively involved in the
      collective invasion and metastasis of PTC.

PMID- 28489071
TI  - Exchange pathways of plastoquinone and plastoquinol in the photosystem II
      complex.
AB  - Plastoquinone (PLQ) acts as an electron carrier between photosystem II (PSII) and
      the cytochrome b6f complex. To understand how PLQ enters and leaves PSII, here we
      show results of coarse grained molecular dynamics simulations of PSII embedded in
      the thylakoid membrane, covering a total simulation time of more than 0.5 ms. The
      long time scale allows the observation of many spontaneous entries of PLQ into
      PSII, and the unbinding of plastoquinol (PLQol) from the complex. In addition to
      the two known channels, we observe a third channel for PLQ/PLQol diffusion
      between the thylakoid membrane and the PLQ binding sites. Our simulations point
      to a promiscuous diffusion mechanism in which all three channels function as
      entry and exit channels. The exchange cavity serves as a PLQ reservoir. Our
      simulations provide a direct view on the exchange of electron carriers, a key
      step of the photosynthesis machinery.

PMID- 28489072
TI  - Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects
      after systemic administration.
AB  - Oncogenic Ras mutants, frequently detected in human cancers, are high-priority
      anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with
      small molecules has been extremely challenging. Here we report the development of
      a human IgG1 format antibody, RT11, which internalizes into the cytosol of living
      cells and selectively binds to the activated GTP-bound form of various oncogenic
      Ras mutants to block the interactions with effector proteins, thereby suppressing
      downstream signalling and exerting anti-proliferative effects in a variety of
      tumour cells harbouring oncogenic Ras mutants. When systemically administered, an
      RT11 variant with an additional tumour-associated integrin binding moiety for
      tumour tissue targeting significantly inhibits the in vivo growth of oncogenic
      Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours.
      Our results demonstrate the feasibility of developing therapeutic antibodies for
      direct targeting of cytosolic proteins that are inaccessible using current
      antibody technology.

PMID- 28489073
TI  - Genetic diversity and gene flow decline with elevation in montane mayflies.
AB  - Montane environments around the globe are biodiversity 'hotspots' and important
      reservoirs of genetic diversity. Montane species are also typically more
      vulnerable to environmental change than their low-elevation counterparts due to
      restricted ranges and dispersal limitations. Here we focus on two abundant
      congeneric mayflies (Baetis bicaudatus and B. tricaudatus) from montane streams
      over an elevation gradient spanning 1400 m. Using single-nucleotide polymorphism
      genotypes, we measured population diversity and vulnerability in these two
      species by: (i) describing genetic diversity and population structure across
      elevation gradients to identify mechanisms underlying diversification; (ii)
      performing spatially explicit landscape analyses to identify environmental
      drivers of differentiation; and (iii) identifying outlier loci hypothesized to
      underlie adaptive divergence. Differences in the extent of population structure
      in these species were evident depending upon their position along the elevation
      gradient. Heterozygosity, effective population sizes and gene flow all declined
      with increasing elevation, resulting in substantial population structure in the
      higher elevation species (B. bicaudatus). At lower elevations, populations of
      both species are more genetically similar, indicating ongoing gene flow.
      Isolation by distance was detected at lower elevations only, whereas landscape
      barriers better predicted genetic distance at higher elevations. At higher
      elevations, dispersal was restricted due to landscape effects, resulting in
      greater population isolation. Our results demonstrate differentiation over small
      spatial scales along an elevation gradient, and highlight the importance of
      preserving genetic diversity in more isolated high-elevation populations.

PMID- 28489074
TI  - Analysis of renal cancer cell lines from two major resources enables genomics
      guided cell line selection.
AB  - The utility of cancer cell lines is affected by the similarity to endogenous
      tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from
      the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three
      renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell
      carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary
      (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as
      kidney chromophobe) renal cell carcinoma. Clustering copy number alterations
      shows that most cell lines resemble ccRCC, a few (including some often used as
      models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours
      clustering with cell lines display clinical and genomic features of more
      aggressive disease, suggesting that cell lines best represent aggressive tumours.
      We stratify mutations and copy number alterations for important kidney cancer
      genes by the consistency between databases, and classify cell lines into
      established gene expression-based indolent and aggressive subtypes. Our results
      could aid investigators in analysing appropriate renal cancer cell lines.

PMID- 28489075
TI  - Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of
      siRNA to Ras-activated glioblastoma cells via macropinocytosis.
AB  - Hyperactivated Ras regulates many oncogenic pathways in several malignant human
      cancers including glioblastoma and it is an attractive target for cancer
      therapies. Ras activation in cancer cells drives protein internalization via
      macropinocytosis as a key nutrient-gaining process. By utilizing this unique
      endocytosis pathway, here we create a biologically inspired nanostructure that
      can induce cancer cells to 'drink drugs' for targeting activating transcription
      factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in
      glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to
      encapsulate the siRNA-loaded calcium phosphate core and facilitate it to
      penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a
      macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts
      remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and
      inhibits tumour cell growth both in vitro and in xenograft tumour models. This
      strategy of targeting the macropinocytosis caused by Ras activation provides a
      nanoparticle-based approach for precision therapy in glioblastoma and other Ras
      activated cancers.

PMID- 28489076
TI  - HLA-DP84Gly constitutively presents endogenous peptides generated by the class I
      antigen processing pathway.
AB  - Classical antigen processing leads to the presentation of antigenic peptides
      derived from endogenous and exogenous sources for MHC class I and class II
      molecules, respectively. Here we show that, unlike other class II molecules,
      prevalent HLA-DP molecules with beta-chains encoding Gly84 (DP84Gly)
      constitutively present endogenous peptides. DP84Gly does not bind invariant chain
      (Ii) via the class II-associated invariant chain peptide (CLIP) region, nor does
      it present CLIP. However, Ii does facilitate the transport of DP84Gly from the
      endoplasmic reticulum (ER) to the endosomal/lysosomal pathway by transiently
      binding DP84Gly via a non-CLIP region(s) in a pH-sensitive manner. Accordingly,
      like class I, DP84Gly constitutively presents endogenous peptides processed by
      the proteasome and transported to the ER by the transporter associated with
      antigen processing (TAP). Therefore, DP84Gly, found only in common chimpanzees
      and humans, uniquely uses both class I and II antigen-processing pathways to
      present peptides derived from intracellular and extracellular sources.

PMID- 28489077
TI  - Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle
      docking and priming.
AB  - The presynaptic active zone protein Munc13 is essential for neurotransmitter
      release, playing key roles in vesicle docking and priming. Mechanistically, it is
      thought that the C2A domain of Munc13 inhibits the priming function by
      homodimerization, and that RIM disrupts the autoinhibitory homodimerization
      forming monomeric priming-competent Munc13. However, it is unclear whether the
      C2A domain mediates other Munc13 functions in addition to this inactivation
      activation switch. Here, we utilize mutations that modulate the homodimerization
      and heterodimerization states to define additional roles of the Munc13 C2A
      domain. Using electron microscopy and electrophysiology in hippocampal cultures,
      we show that the C2A domain is critical for additional steps of vesicular
      release, including vesicle docking. Optimal vesicle docking and priming is only
      possible when Munc13 heterodimerizes with RIM via its C2A domain. Beyond being a
      switching module, our data suggest that the Munc13-RIM heterodimer is an active
      component of the vesicle docking, priming and release complex.

PMID- 28489078
TI  - Hybrid supercapacitors for reversible control of magnetism.
AB  - Electric field tuning of magnetism is one of the most intensely pursued research
      topics of recent times aiming at the development of new-generation low-power
      spintronics and microelectronics. However, a reversible magnetoelectric effect
      with an on/off ratio suitable for easy and precise device operation is yet to be
      achieved. Here we propose a novel route to robustly tune magnetism via the
      charging/discharging processes of hybrid supercapacitors, which involve
      electrostatic (electric-double-layer capacitance) and electrochemical
      (pseudocapacitance) doping. We use both charging mechanisms-occurring at the
      La0.74Sr0.26MnO3/ionic liquid interface to control the balance between
      ferromagnetic and non-ferromagnetic phases of La1-xSrxMnO3 to an unprecedented
      extent. A magnetic modulation of up to ~33% is reached above room temperature
      when applying an external potential of only about 2.0 V. Our case study intends
      to draw attention to new, reversible physico-chemical phenomena in the rather
      unexplored area of magnetoelectric supercapacitors.

PMID- 28489080
TI  - ERRATUM: Medical morbidities and DNA methylation of NR3C1 in preterm infants.

PMID- 28489079
TI  - TRPV1 channels are critical brain inflammation detectors and neuropathic pain
      biomarkers in mice.
AB  - The capsaicin receptor TRPV1 has been widely characterized in the sensory system
      as a key component of pain and inflammation. A large amount of evidence shows
      that TRPV1 is also functional in the brain although its role is still debated.
      Here we report that TRPV1 is highly expressed in microglial cells rather than
      neurons of the anterior cingulate cortex and other brain areas. We found that
      stimulation of microglial TRPV1 controls cortical microglia activation per se and
      indirectly enhances glutamatergic transmission in neurons by promoting
      extracellular microglial microvesicles shedding. Conversely, in the cortex of
      mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting
      their intrinsic electrical properties and synaptic strength. Altogether, these
      findings identify brain TRPV1 as potential detector of harmful stimuli and a key
      player of microglia to neuron communication.

PMID- 28489082
TI  - Experimental test of photonic entanglement in accelerated reference frames.
AB  - The unification of the theory of relativity and quantum mechanics is a long
      standing challenge in contemporary physics. Experimental techniques in quantum
      optics have only recently reached the maturity required for the investigation of
      quantum systems under the influence of non-inertial motion, such as being held at
      rest in gravitational fields, or subjected to uniform accelerations. Here, we
      report on experiments in which a genuine quantum state of an entangled photon
      pair is exposed to a series of different accelerations. We measure an
      entanglement witness for g-values ranging from 30 mg to up to 30 g-under free
      fall as well on a spinning centrifuge-and have thus derived an upper bound on the
      effects of uniform acceleration on photonic entanglement.

PMID- 28489083
TI  - Exploring biomolecular energy landscapes.
AB  - The potential energy landscape perspective provides both a conceptual and a
      computational framework for predicting, understanding and designing molecular
      properties. In this Feature Article, we highlight some recent advances that
      greatly facilitate structure prediction and analysis of global thermodynamics and
      kinetics in proteins and nucleic acids. The geometry optimisation procedures, on
      which these calculations are based, can be accelerated significantly using local
      rigidification of selected degrees of freedom, and through implementations on
      graphics processing units. Results of progressive local rigidification are first
      summarised for trpzip1, including a systematic analysis of the heat capacity and
      rearrangement rates. Benchmarks for all the essential optimisation procedures are
      then provided for a variety of proteins. Applications are then illustrated from a
      study of how mutation affects the energy landscape for a coiled-coil protein, and
      for transitions in helix morphology for a DNA duplex. Both systems exhibit an
      intrinsically multifunnel landscape, with the potential to act as biomolecular
      switches.

PMID- 28489084
TI  - Observation of crystalline changes of titanium dioxide during lithium insertion
      by visible spectrum analysis.
AB  - Real-time analysis of changes in the atomic environment of materials is a cutting
      edge technology that is being used to explain reaction dynamics in many fields of
      science. Previously, this kind of analysis was only possible using heavy
      nucleonic equipment such as XANES and EXAFS, or Raman spectroscopy on a moderate
      scale. Here, a new methodology is described that can be used to track changes in
      crystalline developments during complex Li insertion reactions via the
      observation of structural color. To be specific, the changes in atomic
      crystalline and nanostructure are shown during Li insertion in a complex TiO2
      polymorph. Structural color corresponds to the refractive indices of materials
      originating from their atomic bonding nature and precise wave interferences in
      accordance with their nanostructure. Therefore, this new analysis simultaneously
      reveals changes in the nanostructure as well as changes in the atomic bonding
      nature of materials.

PMID- 28489085
TI  - Intrinsic and light-induced nonadiabatic phenomena in the NaI molecule.
AB  - Nonadiabatic effects play a very important role in controlling chemical dynamical
      processes. They are strongly related to avoided crossings (AC) or conical
      intersections (CIs) which can either be present naturally or induced by classical
      laser light in a molecular system. The latter are named as "light-induced avoided
      crossings" (LIACs) and "light-induced conical intersections" (LICIs). By
      performing one or two dimensional quantum dynamical calculations LIAC and LICI
      situations can easily be created even in diatomic molecules. Applying such
      calculations for the NaI molecule, which is a strongly coupled diatomic in field
      free case, significant differences between the impact of the LIAC and LICI on the
      ground state population dynamics were observed. Moreover, obtained results
      undoubtedly demonstrate that the effect of the LIAC and LICI on the dynamics
      strongly depends on the intensity and the frequency of the applied laser field as
      well as the permanent dipole moments of the molecule.

PMID- 28489086
TI  - Molecular dynamics approach to understand the denaturing effect of a millimolar
      concentration of dodine on a lambda-repressor and counteraction by trehalose.
AB  - Commonly used denaturants for protein denaturation are conventionally required in
      high concentrations in order to produce their effects. In this study, a molecular
      dynamics simulation of a mutated version of the N-terminal domain of a lambda
      repressor is carried out in the presence of a 10 millimolar (mM) concentration of
      dodine. Such a small concentration is found to be effective for denaturation of
      the protein. Both electrostatic and van der Waals interactions (between protein
      and dodine) play a role in the denaturation process and we observe more
      denaturation at the terminal helices. Three different molar concentrations of
      trehalose are used in order to check the counteraction against the action of
      dodine. This study shows that 0.5 and 1.0 M trehalose are sufficient to
      counteract the action of dodine. The study also sheds light on the fact that some
      protein sites are more responsive to unfolding, which is evident from the helical
      fractions of the terminal helices for different systems. The counteraction of
      trehalose on dodine-induced protein denaturation is found to be due to the
      replacement of some of the dodine molecules by trehalose molecules in the
      solvation shell of the protein. Preferential solvation of dodine molecules by
      trehalose molecules through hydrogen bonding interactions also plays a vital role
      in stabilizing the native conformation of the protein in a high trehalose
      concentration. Replacement of protein-dodine and protein-water hydrogen bonds by
      protein-trehalose hydrogen bonds is also observed.

PMID- 28489087
TI  - Hydrolysis of cephalexin and meropenem by New Delhi metallo-beta-lactamase: the
      substrate protonation mechanism is drug dependent.
AB  - Emergence of antibiotic resistance due to New Delhi metallo-beta-lactamase (NDM
      1) bacterial enzymes is of great concern due to their ability to hydrolyze a wide
      range of antibiotics. There are ongoing efforts to obtain the atomistic details
      of the hydrolysis mechanism in order to develop inhibitors for NDM-1. In
      particular, it remains elusive how drug molecules of different families of
      antibiotics are hydrolyzed by NDM-1 in an efficient manner. Here we report the
      detailed molecular mechanism of NDM-1 catalyzed hydrolysis of cephalexin, a
      cephalosporin family drug, and meropenem, a carbapenem family drug. This study
      employs molecular dynamics (MD) simulations using hybrid quantum
      mechanical/molecular mechanical (QM/MM) methods at the density functional theory
      (DFT) level, based on which reaction pathways and the associated free energies
      are obtained. We find that the mechanism and the free energy barrier for the ring
      opening step are the same for both the drug molecules, while the subsequent
      protonation step differs. In particular, we observe that the mechanism of the
      protonation step depends on the R2 group of the drug molecule. Our simulations
      show that allylic carbon protonation occurs in the case of the cephalexin drug
      molecule where Lys211 is the proton donor, and the proton transfer occurs via a
      water chain formed (only) at the ring-opened intermediate structure. Based on the
      free energy profiles, the overall kinetics of drug hydrolysis is discussed.
      Finally, we show that the proposed mechanisms and free energy profiles could
      explain various experimental observations.

PMID- 28489088
TI  - CFA-4 - a fluorinated metal-organic framework with exchangeable interchannel
      cations.
AB  - The syntheses and crystal structures of the fluorinated linker 1,4-bis(3,5
      bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene (H2-tfpb; 1) and the novel metal
      organic framework family M[CFA-4] (Coordination Framework Augsburg University-4),
      M[Cu5(tfpb)3] (M = Cu(i), K, Cs, Ca(0.5)), are described. The ligand 1 is fully
      characterized by single crystal X-ray diffraction, photoluminescence-, NMR-, IR
      spectroscopy, and mass spectrometry. The copper(i)-containing MOF crystallizes in
      the hexagonal crystal system within the chiral space group P6322 (no. 182) and
      the unit cell parameters are as follows: a = 23.630(5) A, c = 41.390(5) A, V = 20
      015(6) A3. M[CFA-4] features a porous 3-D structure constructed from pentanuclear
      copper(i) secondary building units {Cu(pz)6}- (pz = pyrazolate). Cu(I)[CFA-4] is
      fully characterized by synchrotron single crystal X-ray diffraction,
      thermogravimetric analysis, variable temperature powder X-ray diffraction, IR
      spectroscopy, photoluminescence and gas sorption measurements. Moreover, thermal
      stability and gas sorption properties of K[CFA-4] and Cu(I)[CFA-4] are compared.

PMID- 28489089
TI  - Microscale solid-state thermal diodes enabling ambient temperature thermal
      circuits for energy applications.
AB  - Thermal diodes, or devices that transport thermal energy asymmetrically,
      analogous to electrical diodes, hold promise for thermal energy harvesting and
      conservation, as well as for phononics or information processing. The junction of
      a phase change material and phase invariant material can form a thermal diode;
      however, there are limited constituent materials available for a given target
      temperature, particularly near ambient. In this work, we demonstrate that a micro
      and nanoporous polystyrene foam can house a paraffin-based phase change material,
      fused to PMMA, to produce mechanically robust, solid-state thermal diodes capable
      of ambient operation with Young's moduli larger than 11.5 MPa and 55.2 MPa above
      and below the melting transition point, respectively. Moreover, the composites
      show significant changes in thermal conductivity above and below the melting
      point of the constituent paraffin and rectification that is well-described by our
      previous theory and the Maxwell-Eucken model. Maximum thermal rectifications
      range from 1.18 to 1.34. We show that such devices perform reliably enough to
      operate in thermal diode bridges, dynamic thermal circuits capable of
      transforming oscillating temperature inputs into single polarity temperature
      differences - analogous to an electrical diode bridge with widespread
      implications for transient thermal energy harvesting and conservation. Overall,
      our approach yields mechanically robust, solid-state thermal diodes capable of
      engineering design from a mathematical model of phase change and thermal
      transport, with implications for energy harvesting.

PMID- 28489090
TI  - Understanding doping strategies in the design of organic electrode materials for
      Li and Na ion batteries: an electronic structure perspective.
AB  - In this paper, we present a systematic study of the effects of p- and n-doping in
      small molecules on the voltage and capacity of organic electrode materials for
      electrochemical batteries. In particular, coronene, phenalene derivatives as well
      as disodium terephthalate and related fused ring derivatives, representing often
      used building blocks in organic electrode materials, are chosen as model systems.
      We show that p-doping can drastically increase the binding strength to Li or Na
      and is therefore an effective strategy to design organic electrode materials for
      both lithium and sodium ion batteries. It could also be used to increase the
      theoretical capacity. On the other hand, n-doping generally has a much smaller
      effect on the voltage. The effects of n- and p-doping are rationalized based on
      the analysis of changes they induce in the band structure as well as in the
      molecular structure.

PMID- 28489091
TI  - Role of missing carotenoid in reducing the fluorescence of single monomeric
      photosystem II core complexes.
AB  - The fluorescence of monomeric photosystem II core complexes (mPSIIcc) of the
      cyanobacterium Thermosynechococcus elongatus, originating from redissolved
      crystals, is investigated by using single-molecule spectroscopy (SMS) at 1.6 K.
      The emission spectra of individual mPSIIcc are dominated by sharp zero-phonon
      lines, showing the existence of different emitters compatible with the F685,
      F689, and F695 bands reported formerly. The intensity of F695 is reduced in
      single mPSIIcc as compared to single PSIIcc-dimers (dPSIIcc). Crystal structures
      show that one of the beta-carotene (beta-Car) cofactors located at the monomer
      monomer interface in dPSIIcc is missing in mPSIIcc. This beta-Car in dPSIIcc is
      in van der Waals distance to chlorophyll (Chl) 17 in the CP47 subunit. We suggest
      that this Chl contributes to the F695 emitter. A loss of beta-Car cofactors in
      mPSIIcc preparations will lead to an increased lifetime of the triplet state of
      Chl 17, which can explain the reduced singlet emission of F695 as observed in
      SMS.

PMID- 28489092
TI  - Reactivity studies of silylene [PhC(NtBu)2](C5Me5)Si - reactions with [M(COD)Cl]2
      (M = Rh(i), Ir(i)), S, Se, Te, and BH3.
AB  - The reactivity of recently introduced N-heterocyclic silylene
      [PhC(NtBu)2](C5Me5)Si was evaluated. Three different reaction pathways were
      studied: (1) coordination to a Lewis acid, (2) oxidation by chalcogenides, and
      (3) coordination to transition metal complexes. The reaction of the silylene with
      BH3 led to the adduct [PhC(NtBu)2](C5Me5)Si(BH)3. Oxidation with the elemental
      chalcogens sulphur, selenium, and tellurium resulted in the corresponding
      silicon(iv)-chalcogenide compounds [PhC(NtBu)2](C5Me5)SiS,
      [PhC(NtBu)2](C5Me5)SiSe and [PhC(NtBu)2](C5Me5)SiTe. Treatment of the silylene
      with dimeric group 9 transition metal complexes [Ir(COD)Cl]2 and [Rh(COD)Cl]2
      gave square planar coordinated transition metal silylene complexes
      [{PhC(NtBu)2}(C5Me5)Si-Rh(COD)(Cl)] and [{PhC(NtBu)2}(C5Me5)Si-Ir(COD)(Cl)].

PMID- 28489093
TI  - MgAl layered double hydroxide/chitosan porous scaffolds loaded with PFTalpha to
      promote bone regeneration.
AB  - Poor bone formation remains a key risk factor associated with acellular scaffolds
      that occurs in some bone defects, particularly in patients with metabolic bone
      disorders and local osteoporosis. We herein fabricated for the first time layered
      double hydroxide-chitosan porous scaffolds loaded with PFTalpha (LDH-CS-PFTalpha
      scaffolds) as therapeutic bone scaffolds for the controlled release of PFTalpha
      to enhance stem cell osteogenic differentiation and bone regeneration. The LDH-CS
      scaffolds had three-dimensional interconnected macropores, and plate-like LDH
      nanoparticles were uniformly dispersed within or on the CS films. The LDH-CS
      scaffolds exhibited appropriate PFTalpha drug delivery due to hydrogen bonding
      among LDH, CS and PFTalpha. In vitro functional studies demonstrated that the
      PFTalpha molecules exhibited potent ability to induce osteogenesis of hBMSCs via
      the GSK3beta/beta-catenin pathway, and the LDH-CS-PFTalpha scaffolds
      significantly enhanced the osteogenic differentiation of hBMSCs. In vivo studies
      revealed significantly increased repair and regeneration of bone tissue in
      cranial defect model rats compared to control rats at 12 weeks post-implantation.
      In conclusion, the LDH-CS-PFTalpha scaffolds exhibited excellent osteogenic
      differentiation and bone regeneration capability and hold great potential for
      applications in defined local bone regeneration.

PMID- 28489094
TI  - Theoretical insights into the mechanism of ferroptosis suppression via
      inactivation of a lipid peroxide radical by liproxstatin-1.
AB  - Ferroptosis is a recently discovered iron-dependent form of non-apoptotic cell
      death caused by the accumulation of membrane lipid peroxidation products, which
      is involved in various pathological conditions of the brain, kidney, liver and
      heart. A potent spiroquinoxalinamine derivative named liproxstatin-1 is
      discovered by high-throughput screening, which is able to suppress ferroptosis
      via lipid peroxide scavenging in vivo. Thus, molecular simulations, density
      functional theory (DFT) and variational transition-state theory with a small
      curvature tunneling (SCT) coefficient are utilized to elucidate the detailed
      mechanisms of inactivation of a lipid peroxide radical by liproxstatin-1. H-atom
      abstracted from liproxstatin-1 by a CH3OO radical occurs preferentially at the
      aromatic amine site (1'-NH) under thermodynamic and frontier molecular orbital
      analysis. The value of a calculated rate constant at 300 K is up to 6.38 * 103 M
      1 S-1, indicating that the quantum tunneling effect is responsible for making a
      free radical trapping reaction more efficient by liproxstatin-1. The production
      of a liproxstatin-1 radical is easily regenerated to the active reduced form by
      ubiquinol in the body to avoid secondary damage by free radicals. A benzene ring
      and the higher HOMO energy are beneficial to enhance the lipid radical scavenging
      activity based on the structure-activity relationship study. Overall, the present
      results provide theoretical insights into the exploration of novel ferroptosis
      inhibitors.

PMID- 28489095
TI  - Metrology of DNA arrays by super-resolution microscopy.
AB  - Recent results in the assembly of DNA into structures and arrays with nanoscale
      features and patterns have opened the possibility of using DNA for sub-10 nm
      lithographic patterning of semiconductor devices. Super-resolution microscopy is
      being actively developed for DNA-based imaging and is compatible with inline
      optical metrology techniques for high volume manufacturing. Here, we combine DNA
      tile assembly with state-dependent super-resolution microscopy to introduce
      crystal-PAINT as a novel approach for metrology of DNA arrays. Using this
      approach, we demonstrate optical imaging and characterization of DNA arrays
      revealing grain boundaries and the temperature dependence of array quality. For
      finite arrays, analysis of crystal-PAINT images provides further quantitative
      information of array properties. This metrology approach enables defect detection
      and classification and facilitates statistical analysis of self-assembled DNA
      nanostructures.

PMID- 28489096
TI  - Physical principles for DNA tile self-assembly.
AB  - DNA tiles provide a promising technique for assembling structures with nanoscale
      resolution through self-assembly by basic interactions rather than top-down
      assembly of individual structures. Tile systems can be programmed to grow based
      on logical rules, allowing for a small number of tile types to assemble large,
      complex assemblies that can retain nanoscale resolution. Such algorithmic systems
      can even assemble different structures using the same tiles, based on inputs that
      seed the growth. While programming and theoretical analysis of tile self-assembly
      often makes use of abstract logical models of growth, experimentally implemented
      systems are governed by nanoscale physical processes that can lead to very
      different behavior, more accurately modeled by taking into account the
      thermodynamics and kinetics of tile attachment and detachment in solution. This
      review discusses the relationships between more abstract and more physically
      realistic tile assembly models. A central concern is how consideration of model
      differences enables the design of tile systems that robustly exhibit the desired
      abstract behavior in realistic physical models and in experimental
      implementations. Conversely, we identify situations where self-assembly in
      abstract models can not be well-approximated by physically realistic models,
      putting constraints on physical relevance of the abstract models. To facilitate
      the discussion, we introduce a unified model of tile self-assembly that clarifies
      the relationships between several well-studied models in the literature.
      Throughout, we highlight open questions regarding the physical principles for DNA
      tile self-assembly.

PMID- 28489097
TI  - Self-assembly of inverse patchy colloids with tunable patch coverage.
AB  - We report a simple and scalable technique for the preparation of patchy particles
      with tunable patch coverage. These particles are categorized as inverse patchy
      colloidal particles (IPCs) as the patches repel each other while patch and non
      patch surfaces attract. We demonstrate the effect of patch coverage,
      concentration of electrolyte and concentration of particles on the self-assembly
      of IPC particles. The study identifies various clustering zones such as (1)
      finite-sized clusters, (2) chain-like assemblies and (3) irregular amorphous
      aggregates. The linear assemblies are observed over a wide range of particle
      concentrations and salt concentrations. The anisotropic electrostatic interaction
      controls the formation of chain-like assemblies. In an extended study, we use
      negatively charged isotropic colloidal (NCIC) particles to tune the self-assembly
      of IPC particles. Interestingly, we observe significant improvement in the
      clustering efficiency of IPC particles leading to the formation of co-polymeric,
      flexible branched chains. Depending on the number ratio of NCIC particles with
      respect to IPC particles, the clustering process is classified into three
      different phases such as (1) finite-sized, (2) linear and (3) dispersed state.
      Using a quantitative analysis we show that such evolution of structures is
      attributed to seeding and crowding effects caused by the addition of NCIC
      particles. The use of NCIC particles thus control the self-assembly of inverse
      patchy colloids and tune the number and shape of the self-assembled structures.

PMID- 28489098
TI  - Correction: Distinctive hippocampal zinc distribution patterns following stress
      exposure in an animal model of PTSD.
AB  - Correction for 'Distinctive hippocampal zinc distribution patterns following
      stress exposure in an animal model of PTSD' by Hagit Sela et al., Metallomics,
      2017, 9, 323-333.

PMID- 28489099
TI  - Dual-core star-shaped single white polymers: the effect of host structure on
      luminescence properties.
AB  - The non-emissive benzene ring and green-emissive arylmaleimide are employed as
      two independent cores to construct dual-core white star-shaped polymers (DC
      PFMs). Due to the totally star-shaped structure, DC-PFMs display a higher quantum
      yield and electroluminescence efficiency for a more efficient energy transfer
      from the host to the guest than traditional single-core polymers (SC-PFMs).

PMID- 28489100
TI  - A copper-phosphonate network as a high-performance heterogeneous catalyst for the
      CO2 cycloaddition reactions and alcoholysis of epoxides.
AB  - A novel 3D copper-phosphonate network, with the general formula
      Cu7(H1L)2(TPT)3(H2O)6, namely compound 1, has been synthesized using a rigid
      tetrahedral linker tetraphenylsilane tetrakis-4-phosphonic acid (H8L) and a
      nitrogen-containing ancillary ligand (TPT: [5-(4-(1H-1,2,4-triazol-1-yl)phenyl)
      1H-tetrazole]) under hydrothermal conditions. The compound was fully
      characterized using PXRD, ICP, IR, TGA and elemental analysis. Compound 1 can be
      used as an efficient catalyst for the CO2 coupling reaction that is greatly
      superior to many conventional MOF-based catalysts, where porosity is always
      mentioned and used. In addition, it shows excellent catalytic performance for
      ring-opening reactions with epoxides under ambient conditions. Additionally,
      compound 1 can be recycled at least three times without a significant compromise
      in the activity in the two catalytic reactions.

PMID- 28489101
TI  - Direct experimental observation of mesoscopic fluorous domains in fluorinated
      room temperature ionic liquids.
AB  - Fluorinated room temperature ionic liquids (FRTILs) represent a class of solvent
      media that are attracting great attention due to their IL-specific properties as
      well as features stemming from their fluorous nature. Medium-to-long fluorous
      tails constitute a well-defined apolar moiety in the otherwise polar environment.
      Similarly to the case of alkyl tails, such chains are expected to result in the
      formation of self-assembled fluorous domains. So far, however, no direct
      experimental observation has been made of the existence of such structural
      heterogeneities on the nm scale. We report here the first experimental evidence
      of the existence of mesoscopic spatial segregation of fluorinated domains, on the
      basis of highly complementary X-ray and neutron scattering data sets
      (highlighting the importance of the latter probe) and NMR spectroscopy. Data are
      interpreted using atomistic molecular dynamics simulations, emphasizing the
      existence of a self-assembly mechanism that delivers segregated fluorous domains,
      where preferential solubilisation of fluorinated compounds can occur, thus paving
      the way for several smart applications.

PMID- 28489102
TI  - Temperature-modulated crystal growth and performance for highly reproducible and
      efficient perovskite solar cells.
AB  - The annealing temperature (Ta) effect on CH3NH3PbI3 perovskite solar cells (PSCs)
      was studied. By utilizing a two-step technique, the Ta dependences of the optical
      absorption, grain size, and crystallinity of a CH3NH3PbI3 thin film have been
      revealed. It is found that the grain size of the CH3NH3PbI3 film increases
      monotonically with Ta. Meanwhile, the decomposed PbI2 emerges when Ta exceeds 120
      degrees C and its content increases rapidly as Ta increases further.
      Consequently, the optical absorption of the CH3NH3PbI3 film and the efficiency of
      PSCs reach their maximum at Ta = 120  degrees C simultaneously. The highest and
      average device performances of PSCs achieved via this method are 17.61% and
      16.40%, respectively. These results confirm the key role played by temperature
      and provide a route to the performance-optimization of PSCs.

PMID- 28489103
TI  - Triethanolamine doped multilayer MoS2 field effect transistors.
AB  - Chemical doping has been investigated as an alternative method of conventional
      ion implantation for two-dimensional materials. We herein report chemically doped
      multilayer molybdenum disulfide (MoS2) field effect transistors (FETs) through n
      type channel doping, wherein triethanolamine (TEOA) is used as an n-type dopant.
      As a result of the TEOA doping process, the electrical performances of multilayer
      MoS2 FETs were enhanced at room temperature. Extracted field effect mobility was
      estimated to be ~30 cm2 V-1 s-1 after the surface doping process, which is 10
      times higher than that of the pristine device. Subthreshold swing and contact
      resistance were also improved after the TEOA doping process. The enhancement of
      the subthreshold swing was demonstrated by using an independent FET model.
      Furthermore, we found that the doping level can be effectively controlled by the
      heat treatment method. These results demonstrate a promising material system that
      is easily controlled with high performance, while elucidating the underlying
      mechanism of improved electrical properties by the doping effect in a
      multilayered scheme.

PMID- 28489104
TI  - Spatially-resolved profiling of carbon nanotube uptake across cell lines.
AB  - The internalisation and intra-cellular distribution of carbon nanotubes (CNT) has
      been quantitatively assessed using imaging flow cytometry. Spatial analysis of
      the bright field images indicates the presence of a small sub-population (5% of
      cells) in which the internalised CNTs are packed into pronounced clusters,
      visible as dark spots due to strong optical scattering by the nanotubes. The area
      of these spots can be used as a label-free metric of CNT dose and we assess the
      relative uptake of charge-neutral CNTs, over a 24 hours exposure period across
      four cell types: J774 mouse macrophage cells, A549 and Calu-6 human lung cancer
      cells, and MCF-7 human breast cells. The relative dose as indicated by the spot
      area metric closely correlates to results using the same CNT preparation,
      conjugated to a FITC-label and shows pronounced uptake by the J774 cells leading
      to a mean dose that is >60% higher than for the other cell types. Spatial
      evaluation of dosing clusters is also used to quantify differences in uptake by
      J774 cells of CNTs with different surface functionalisation. While the percentage
      of CNT-cluster positive cells increases from 5% to 19% when switching from charge
      neutral CNTs to poly-cationic, dendron functionalised CNTs, the single cell level
      analysis of internalised clusters indicates a lower dose per cell of poly
      cationic CNTs relative to the charge-neutral CNTs. We concluded that there is
      dose homeostasis i.e., the population-averaged cellular dose of CNTs remained
      unchanged.

PMID- 28489105
TI  - Chirality as a tool for function in porous organic cages.
AB  - The control of solid state assembly for porous organic cages is more challenging
      than for extended frameworks, such as metal-organic frameworks. Chiral
      recognition is one approach to achieving this control. Here we investigate chiral
      analogues of cages that were previously studied as racemates. We show that chiral
      cages can be produced directly from chiral precursors or by separating racemic
      cages by co-crystallisation with a second chiral cage, opening up a route to
      producing chiral cages from achiral precursors. These chiral cages can be
      cocrystallized in a modular, 'isoreticular' fashion, thus modifying porosity,
      although some chiral pairings require a specific solvent to direct the crystal
      into the desired packing mode. Certain cages are shown to interconvert chirality
      in solution, and the steric factors governing this behavior are explored both by
      experiment and by computational modelling.

PMID- 28489106
TI  - Quantitative relationship between fluid inhomogeneities and flow enhancement in
      nanotubes.
AB  - Flow enhancement in nanotubes is of great potential to achieve ultra-fast fluidic
      transport. However, the mechanism of such a fast transport and the reduction as
      the tube enlarges to bulk scale is still unclear. In this study, we establish a
      model to quantitatively correlate the flow enhancement and the fluid
      inhomogeneity to describe the enhanced transport and its evolution with the tube
      dimension. We found the fluid inhomogeneity at the solid-liquid interface in
      nanotubes and its independence with tube size by dissipative particle dynamics
      (DPD) simulation. Based on that, we establish novel theoretical models for the
      penetration rate in nanotubes for the first time with parameters related to the
      fluid inhomogeneity which can achieve quantitative prediction of nanoflow
      enhancement and are valid through all scales.

PMID- 28489107
TI  - A novel metal-free method for the selenocyanation of aromatic ketones to afford
      alpha-carbonyl selenocyanates.
AB  - A new method has been developed for the selenocyanation of aromatic ketones. This
      reaction avoids the need to use pre-prepared alpha-halo ketones, providing rapid
      access to alpha-carbonyl selenocyanates. We also investigated the mechanism for
      this reaction and found that it proceeds via sequential radical iodination and
      nucleophilic substitution reactions.

PMID- 28489109
TI  - Statistical theory of polarizable target compound impregnation into a polymer
      coil under the influence of an electric field.
AB  - The paper presents a theoretical approach for describing the influence of an
      electric field on the conformation of an electrically neutral dielectric polymer
      chain dissolved in a dielectric solvent with an admixture of a target compound.
      Each monomer and each molecule of the target compound carries positive excess
      polarizability and the solvent is described as a continuous dielectric medium.
      The model is based on the Flory-type mean-field theory. We demonstrate non
      monotonic dependences of the expansion factor and the concentration of the target
      compound on the strength of the electric field and molecular polarizability.
      Namely, the target compound concentration in the internal polymer volume as a
      function of electric field strength has pronounced maxima if the molecules are
      polarizable. In addition, the expansion factor of the non-polarizable polymer
      chain can be controlled by the electric field. The dependences of the expansion
      factor and target compound concentration on the monomer polarizability exhibit
      minima and intersection points. The intersection points correspond to the
      equality of dielectric permittivities in the bulk solution and in the internal
      polymer volume.

PMID- 28489111
TI  - Layer-dependent electronic properties of phosphorene-like materials and
      phosphorene-based van der Waals heterostructures.
AB  - Black phosphorus is a layered semiconducting allotrope of phosphorus with high
      carrier mobility. Its monolayer form, phosphorene, is an extremely fashionable
      two-dimensional material which has promising potential in transistors,
      optoelectronics and electronics. However, phosphorene-like analogues, especially
      phosphorene-based heterostructures and their layer-controlled electronic
      properties, are rarely systematically investigated. In this paper, the layer
      dependent structural and electronic properties of phosphorene-like materials,
      i.e., mono- and few-layer MXs (M = Sn, Ge; X = S, Se), are first studied via
      first-principles calculations, and then the band edge position of these MXs as
      well as mono- and few-layer phosphorene are aligned. It is revealed that van der
      Waals heterostructures with a Moire superstructure formed by mutual coupling
      among MXs and among MXs and few-layer phosphorene are able to show type-I or type
      II characteristics and a I-II or II-I transition can be induced by adjusting the
      number of layers. Our work is expected to yield a new family of phosphorene-based
      semiconductor heterostructures with tunable electronic properties through
      altering the number of layers of the composite.

PMID- 28489112
TI  - An efficient charge separation and photocurrent generation in the carbon dot-zinc
      oxide nanoparticle composite.
AB  - The development of light harvesting systems based on heterostructures for
      efficient conversion of solar energy to renewable energy is an emerging area of
      research. Here, we have designed heterostructures by using carbon dots (C-dots)
      and zinc oxide nanoparticles (ZnO NP) to develop an efficient light harvesting
      system. Interestingly, the conduction band and the valence band positions of ZnO
      NP are lower than the LUMO and HOMO positions of C-dots in this type II
      heterostructure of C dot-ZnO NP, which causes efficient charge separation and
      photocurrent generation. Steady state and time resolved spectroscopic studies
      reveal that an efficient photoinduced electron transfer occurs from C dots to ZnO
      NP and a simultaneous hole transfer occurs from the valence band of ZnO NP to the
      HOMO of C dots. The calculated rate of electron transfer is found to be 3.7 * 109
      s-1 and the rate of hole transfer is found to be 3.6 * 107 s-1. The enhancement
      of photocurrent (11 fold) under solar light irradiation of the C dot-ZnO NP
      heterostructure opens up new possibilities to design efficient light harvesting
      systems.

PMID- 28489114
TI  - Physical chemistry in a single live cell: confocal microscopy.
AB  - A live cell is a complex, yet extremely important container. Understanding the
      dynamics in a selected intracellular component is a challenging task. We have
      recently made significant progress in this direction using a confocal microscope
      as a tool. The smallest size of the focused spot in a confocal microscope is ~0.2
      MUm (200 nm). This is nearly one hundred times smaller than the size of a live
      cell. Thus, one can selectively study different intracellular
      components/organelles in a live cell. In this paper, we discuss how one can image
      different intracellular components/organelles, record fluorescence spectra and
      decay at different locations, ascertain local polarity and viscosity, and monitor
      the dynamics of solvation, proton transfer, red-ox and other phenomena at
      specified locations/organelles inside a cell. We will highlight how this
      knowledge enriched us in differentiating between cancer and non-cancer cells, 3D
      tumor spheroids and towards drug delivery.

PMID- 28489116
TI  - Investigation of the push-pull effects on beta-functionalized benzoporphyrins
      bearing an ethynylphenyl bridge.
AB  - A series of beta-pyrrole functionalized push-pull porphyrins with amine push
      groups linked via an ethynylphenyl spacer, and cyclic imide or carboxylic esters
      as pull groups have been newly synthesized and characterized. The beta-pyrrole
      functionalized ethynylphenyl spacer extends the conjugation of the porphyrin pi
      system, as reflected by their red-shifted absorbance and fluorescence spectra.
      The computed structures revealed no steric hindrance between the porphyrin pi
      system and the beta-substituents. The calculated HOMO and LUMO of compounds WJ2
      and WJ3 display significant segregation, where the electron density in the HOMO
      and LUMO is mainly located at the donor component and the acceptor component,
      respectively. The orbital segregation is likely attributed to the introduction of
      the electron-donating amine group at the porphyrin periphery. Electrochemical
      studies revealed the expected lower HOMO-LUMO gap as a result of the facile
      oxidation and reduction of the push-pull porphyrins. As a consequence of the push
      pull effects, a reduction in fluorescence intensity and lifetime was observed,
      especially for compound WJ3 having two electron-donating amino groups and a
      strongly electron-withdrawing cyclic imide group. Femtosecond transient
      absorption spectral studies revealed the successful formation of the singlet
      excited state in all of these push-pull porphyrins. Due to the occurrence of
      intramolecular charge transfer-type interactions, relaxation of the singlet
      excited state was found to be faster in compound WJ3 compared to other two
      derivatives in polar solvent but not in nonpolar solvent. Such charge transfer
      type interactions from the triplet excited state were also observed in the case
      of compound WJ3 in benzonitrile. The present findings bring out the importance of
      push-pull effects in governing the ground and excited (singlet and triplet) state
      properties of free-base porphyrins.

PMID- 28489117
TI  - Survival of sealants in molars affected by molar-incisor hypomineralization: 18
      month follow-up.
AB  - The objective of this study was to evaluate the clinical survival of sealants
      applied in first permanent molars (FPMs) affected by molar-incisor
      hypomineralization (MIH), at 18 months of follow-up. Forty-one first permanent
      molars were selected from 21 children, 6-8 years of age. MIH was classified by
      one calibrated examiner (kappa = 0.80) according to EAPD criteria. The inclusion
      criteria were fully erupted FPMs with MIH or sound FPMs (without MIH) for which
      sealant treatment was indicated. The FPMs were assigned to two groups: CG
      (control group) and HG (MIH group). Both groups were treated with sealant
      (FluroShield). Clinical follow-up was performed from baseline to 18 months to
      assess anatomical form, marginal adaptation, retention and presence of caries,
      according to criteria set by the United States Public Health Service-Modified,
      and was conducted by a blinded examiner (kappa = 0.80). The actuarial method was
      used to evaluate the survival of the sealants. The survival rates for the groups
      were compared using Fisher's exact test (alpha = 5%). The cumulative survival
      rates were 81% at 1 month, 68.8% at 6 months, 68.8% at 12 months, and 62.6% at 18
      months for CG, and 88% at 1 month, 84% at 6 months, 76% at 12 months, and 72% at
      18 months for HG. No significant difference was found between the groups. The
      sealants in molars affected by MIH presented a survival rate similar to the
      sealants in the control, suggesting that sealants may be an adequate approach for
      preventing carious lesions in MIH-affected molars.

PMID- 28489118
TI  - Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic
      keratocystic odontogenic tumors.
AB  - The aim of this study was to evaluate the immunoexpression of glucose
      transporters 1 (GLUT-1) and 3 (GLUT-3) in keratocystic odontogenic tumors
      associated with Gorlin syndrome (SKOTs) and non-syndromic keratocystic
      odontogenic tumors (NSKOTs), and to establish correlations with the angiogenic
      index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were
      selected for the study. The percentage of immunopositive cells for GLUT-1 and
      GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic
      index was determined by microvessel count. The results were analyzed
      statistically using the nonparametric Kruskal-Wallis test and Spearman's
      correlation test. High epithelial immunoexpression of GLUT-1 was observed in most
      tumors (p = 0.360). There was a higher frequency of negative cases for GLUT-3 in
      all groups. The few GLUT-3-positive tumors exhibited low expression of this
      protein in epithelial cells. No significant difference in the angiogenic index
      was observed between groups (p = 0.778). GLUT-1 expression did not correlate
      significantly with the angiogenic index (p > 0.05). The results suggest that the
      more aggressive biological behavior of SKOTs when compared to NSKOTs may not be
      related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in
      glucose uptake by epithelial cells of KOTs and this process is unlikely related
      to the angiogenic index. GLUT-1 could be a potential target for future
      development of therapeutic strategies for KOTs.

PMID- 28489119
TI  - Cardiovascular disease in women: are we aware?

PMID- 28489120
TI  - Overactive bladder: pharmacological treatment.

PMID- 28489121
TI  - Diethylpropion and mazindol: An end to the discussion?
AB  - Antiobesity pharmacotherapy remains the main point of disagreement among both
      scientists and regulators. This is probably due to small sample sizes, high
      levels of heterogeneity, and low methodological quality. For many years, Brazil
      was one of the largest consumers of appetite suppressants worldwide, with
      evidence of irrational use of this drug class. Therefore, the country was the
      scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa -
      Agencia Nacional de Vigilancia Sanitaria) and medical societies over the
      maintenance record of diethylpropion, mazindol and fenproporex. In this context,
      this commentary presents new arguments to contribute to the discussion, as well
      as recommendations for future studies.

PMID- 28489122
TI  - Minimally invasive endoscopic treatment of necrotizing pancreatitis: A case
      report with images and review of the literature.
AB  - Necrotizing pancreatitis with fluid collections can occur as a complication of
      acute pancreatitis. The management of these patients depends on the severity and
      involves multiple medical treatment modalities, as clinical intensive care and
      surgical intervention. In this article, we show a severe case of walled-off
      pancreatic necrosis that was conducted by endoscopic drainage with great clinical
      outcome.

PMID- 28489123
TI  - Acute amiodarone toxicity causing respiratory failure.
AB  - A 66-year-old male patient was referred to our clinic with severe pneumonia.
      Bronchoscopy was performed due to clinical worsening despite antibiotics and
      diuretic therapy, respiratory failure and radiographic progression. Because
      bacterial cultures of the bronchoalveolar lavage fluid were negative and after
      using amiodarone for almost one month, we eliminated amiodarone from his
      medication regimen due to suspicion of amiodarone toxicity. Accordingly, we also
      initiated systemic steroid therapy. Chest X-ray done after 72 hours showed a
      significant resolution of lung consolidations and the patient exhibited
      significant clinical improvement, with decline of his oxygen requirements.

PMID- 28489124
TI  - Retroauricular pain caused by Eagle syndrome: A rare presentation due to
      compression by styloid process elongation.
AB  - Eagle syndrome is a rare condition presenting with retroauricular pain (usually
      as main symptom) associated with dysphagia, headache, neck pain on rotation and,
      much rarelier, stroke. This occurs due to styloid process elongation. Sometimes,
      there is also styloid ligament calcification, which can cause compression of
      nerves and arteries and the symptoms above. Treatment can be conservative with
      pain modulators (e.g. pregabalin) or infiltrations (steroids or anesthetics
      drugs). In refractory cases, surgical approach aiming to reduce the size of the
      styloid process can be performed. We present a rare case of Eagle syndrome
      (documented by computed tomography) with good response to clinical treatment.

PMID- 28489125
TI  - Severe hypoproteinemia as a harbinger of Menetrier's disease in autoimmune
      pancreatitis.
AB  - Menetrier's disease is an extremely rare disease of unknown etiology causing
      gastric mucosal hypertrophy and protein-losing gastropathy. Rare cases of this
      condition have been reported in patients with autoimmune diseases. However, to
      the best of our knowledge, Menetrier's disease associated with autoimmune
      pancreatitis (AIP) has never been reported. We described a case of severe
      hypoproteinemia as a harbinger of Menetrier's disease associated with AIP. The
      patient was successfully treated with octreotide and high-protein diet, which led
      to symptomatic remission and significant improvement in serum levels of albumin
      and recovery of the nutritional status. Thus, in AIP patients presenting with
      severe and persistent hypoproteinemia without apparent cause, clinicians need to
      consider Menetrier's disease in the differential diagnosis. In this setting,
      endoscopic evaluation with histological examination of gastric biopsy material,
      including a full-thickness mucosal biopsy of involved mucosa, may be helpful in
      promptly establishing the diagnosis and allowing appropriate and timely therapy.

PMID- 28489126
TI  - Solid pseudopapillary tumor of the pancreas: Clinical features, diagnosis and
      treatment.
AB  - Introduction:: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare
      neoplasm of low malignant potential with uncertain behavior, diagnosed mainly in
      young women. Method:: Our report comprises a series of cases of SPTP reviewed
      retrospectively, highlighting clinical, tomographic and immunohistochemical
      features, treatment performed and outcomes. Results:: Thirteen patients were
      found to have pancreatic [solid] masses on computed tomography scan measuring a
      mean diameter of 8.8 cm. All patients underwent complete surgical excision.
      Immunohistochemistry confirmed diagnosis in all cases. Conclusion:: SPTP occurs
      more frequently in young women. Diagnostic suspicion lies on the finding of a
      bulky, solid and cystic pancreatic mass. Imaging findings might provide
      diagnostic information before resection. Conservative approaches can be used in
      selected cases and survival rates are usually excellent following complete
      resection.

PMID- 28489127
TI  - Genotype 1 of human parvovirus B19 in clinical cases.
AB  - Introduction:: Virus surveillance strategies and genetic characterization of
      human parvovirus B19 (B19V) are important tools for regional and global control
      of viral outbreak. In Sao Paulo, Brazil, we performed a study of B19V by
      monitoring the spread of this virus, which is an infectious agent and could be
      mistakenly reported as a rash and other types of infection. Method:: Serum
      samples were subjected to enzyme immunoassay, real time polymerase chain
      reaction, and sequencing. Results:: From the 462 patients with suspected cases of
      exanthematic infections, the results of the 164 serum samples were positive for
      B19V immunoglobulin M. Among these cases, there were 38 patients with erythema
      infections and B19-associated with other infections such as encephalitis, hydrops
      fetalis, chronic anemia, hematological malignancies. These samples were sequenced
      and identified as genotype 1. Conclusion:: This study showed patients with
      infections caused by B19V and sequencing genotype 1. Continuous monitoring is
      necessary to detect all known genotypes, and the emergence of new genotypes of
      these viruses for case management in public health control activities.

PMID- 28489128
TI  - Obesity, bariatric surgery and oxidative stress.
AB  - Introduction:: Obesity refers to the accumulation of fatty tissues and it favors
      the occurrence of oxidative stress. Alternatives that can contribute to body
      weight reduction have been investigated in order to reduce the production of
      reactive oxygen species responsible for tissue damage. The aim of the current
      study was to assess whether the oxidant and antioxidant markers of obese women
      before and after bariatric surgery were able to reduce oxidative damage. Method::
      We have assessed 16 morbidly obese women five days before and 180 days after the
      surgery. The control group comprised 16 non-obese women. Levels of thiobarbituric
      acid-reactive substances, carbonylated proteins, reduced glutathione and ascorbic
      acid were assessed in the patients' plasma. Results:: Levels of lipid
      peroxidation and protein carbonylation in the pre-surgical obese women were
      higher than those of the controls and post-surgical obese women. Levels of
      reduced glutathione in the pre-surgical obese women were high compared to the
      controls, and declined after surgery. Levels of ascorbic acid fell in the pre-
      surgical obese women compared to the control and post-surgical obese women.
      Conclusion:: Body weight influences the production of reactive oxygen species.
      Bariatric surgery, combined with weight loss and vitamin supplementation, reduces
      cellular oxidation, thus reducing tissue damage.

PMID- 28489129
TI  - Growth velocity and weight gain in prepubertal asthmatic children.
AB  - Objective: : To evaluate the stature growth rate (GR) and the weight gain of
      prepubertal asthmatic children. Method:: A retrospective cohort study evaluating
      medical records of 85 children diagnosed with asthma, aged less than 9 years, of
      both sexes, with at least one year of follow-up in the allergy outpatient clinic.
      The data on the disease, weights and heights were collected through a
      standardized questionnaire on two occasions, with an interval of one year. The
      curves proposed by Tanner were applied for the analysis of the GR, and the Z
      score of the GR (ZGR) was calculated. Results:: Excess weight (risk for
      overweight, overweight and obesity) was observed in 31.8% (27/85) of the
      patients, but there was no association with the severity of asthma. Low GR (ZGR <
      -2) was found in 13.9% (11/79) of patients, most frequently among children with
      moderate/severe persistent asthma compared to persistent mild and intermittent
      forms (7/11 - 63.6% vs. 21/68 - 30.2%, respectively, p=0.047). Use of steroids
      (dose, type and time of use) was not associated with GR. Conclusion:: GR was most
      affected in children with moderate/severe asthma.

PMID- 28489130
TI  - Impact of coronary intensive care unit in treatment of myocardial infarction.
AB  - Introduction: : The mortality rate attributed to ST-segment elevation myocardial
      infarction (STEMI) has decreased in the world. However, this disease is still
      responsible for high costs for health systems. Several factors could decrease
      mortality in these patients, including implementation of cardiac intensive care
      units (CICU). The aim of this study was to evaluate the effect of CICU
      implementation on prescribed recommended treatments and mortality 30 days after
      STEMI. Method:: We performed a retrospective study with patients admitted to CICU
      between 2005 and 2006 (after group) and between 2000 and 2002, before CICU
      implementation (before group). Results:: The after group had 101 patients, while
      the before group had 143 patients. There were no differences in general
      characteristics between groups. We observed an increase in angiotensin-converting
      enzyme inhibitors, clopidogrel and statin prescriptions after CICU
      implementation. We did not find differences regarding number of patients
      submitted to reperfusion therapy; however, there was an increase in primary
      percutaneous angioplasty compared with thrombolytic therapy in the after group.
      There was no difference in 30-day mortality (before: 10.5%; after: 8.9%;
      p=0.850), but prescription of recommended treatments was high in both groups.
      Prescription of angiotensin-converting enzyme inhibitors and beta-blocker
      decreased mortality risk by 4.4 and 4.9 times, respectively. Conclusion:: CICU
      implementation did not reduce mortality after 30 days in patients with STEMI;
      however, it increased the prescription of standard treatment for these patients.

PMID- 28489131
TI  - Incidence of delirium in postoperative patients treated with total knee and hip
      arthroplasty.
AB  - Introduction:: Delirium is a common disorder that can potentiate mortality and
      comorbidity rates of patients hospitalized in intensive care units. Patients
      undergoing major orthopedic surgeries, such as knee and hip arthroplasty, are
      particularly vulnerable as they often have multiple risk factors for this
      disorder. Method: : Descriptive study of the incidence of delirium in patients
      treated with total knee and hip arthroplasty, given the advanced age and
      comorbidities in this population. We evaluated the medical records of patients
      who had previously undergone the designated surgeries for identification of
      postoperative delirium. Results:: We observed in this study an incidence of 8.92%
      of delirium, mostly affecting females with a mean age of 73 years and
      hypertension. Conclusion:: The incidence of delirium in our study is similar to
      that observed in the general population, according to the literature. We found no
      correlation with sleep disorders, smoking or diabetes mellitus in this study,
      even though the importance of these factors for the onset of delirium is well
      established in the literature.

PMID- 28489132
TI  - Patient adherence to ischemic heart disease treatment.
AB  - Introduction:: The effectiveness of the treatment of chronic diseases depends on
      the participation of the patient, influenced by different sociocultural factors,
      which are not fully recognized by the treatment routine. Objective:: To search
      for some of these factors that hinder or facilitate adherence to treatment and
      use of healthcare resources, approaching patients with ischemic heart disease.
      Method:: A cross-sectional study was conducted using face-to-face interviews. We
      applied semi-structured questionnaires to 347 individuals and recorded 141
      interviews for qualitative analysis. Descriptors were selected to identify eight
      categories of analyses. The quantitative data were submitted to descriptive
      analysis of frequency. Results:: Only 2% had good medication adherence according
      to score on Morisky questionnaire. About 23% bought statins; the others obtained
      statin in the public health institution. Thirty-six speeches were selected and
      classified according to the following categories: knowledge about disease and
      medication, difficulty of acquisition, self management of treatment, difficulties
      of access to health services, side effect of statins, caregiver support,
      transportation to health services and concerns about the disease progression.
      However, it was noticed that about 1/3 of the care outside the research
      institution can be characterized as an attempt to bring rationalization to the
      health system. Conclusion:: The improved adherence to chronic treatment of
      ischemic heart disease depends on the establishment of effective flows for
      referral and counter-referral from one care unit to another, relevant information
      and clarification of the questions for the patients and the attention of health
      professionals to the many social and cultural factors involved in treatment
      adherence. New research should be focused on educational groups by integrated
      multidisciplinary teams in order to share treatment decisions, thereby increasing
      the patient's commitment to his own health.

PMID- 28489133
TI  - Association between antipsychotics and cardiovascular adverse events: A
      systematic review.
AB  - Objective: : Determine whether there is an association between the risk of
      cardiovascular adverse events and the use of antipsychotic agents. Method::
      Analysis of original articles retrieved from the following databases: LILACS,
      PubMed, Cochrane Controlled Trials Clinical Data Bank (CENTRAL) and PsycINFO,
      without language restriction, dated until November 2015. After screening of 2,812
      studies, three cohort original articles were selected for quality analysis.
      Results:: 403,083 patients with schizophrenia and 119,015 participants in the
      control group data were analyzed. The occurrence of cardiovascular events
      observed in the articles was: 63.5% (article 1), 13.1% (article 2) and 24.95%
      (article 3) in the group of treated schizophrenic patients, and 46.2%, 86.9% and
      24.9%, respectively, in the control groups. Conclusion:: Clinical heterogeneity
      among the studies led to a provisional response and made it impossible to perform
      the meta-analysis, although the articles demonstrate an association between
      cardiovascular adverse events and the use of antipsychotics. More quality
      clinical trials are needed to support this evidence.

PMID- 28489134
TI  - Dialectics of a medical provision policy in priority areas in Brazil.
AB  - Introduction:: The people living in vulnerable areas that are difficult to access
      in Brazil represent a portion of the population that has proven very sensitive to
      lack of medical and health services. The government, seeking to solve the
      situation urgently, implemented the More Doctors Program [Programa Mais Medicos,
      in the Portuguese original] in 2013. Objective: : To discuss the More Doctors
      Program, with the purpose of contributing to the debate on the provision of
      medical policies in Brazil. Method:: Study based on the review of official
      documents: Programa Mais Medicos - dois anos: mais saude para os brasileiros,
      2015 [More Doctors Program - two years: more health for Brazilians, 2015];
      Operational Audit Report, TC No 005391/2014-8, the Court of Auditors of Brazil;
      and Medical Demography in Brazil 2015. Results:: The import of exchange
      physicians without diploma revalidation has cast a shadow on the technical
      quality of services offered to the population. In terms of infrastructure, the
      reduction of resources paralyzed works and made the care network maintenance
      projects impossible. The creation of new medical schools has created uncertainty
      about the possibility of quality education being offered, with minimum and
      sufficient structure including laboratories, clinics and teaching hospitals
      indispensable to medical training. Conclusion:: The regional inequalities of
      concentration and dispersion of physicians, showed by studies on medical
      demography in Brazil, stem from several factors, including the lack of a career
      path and working conditions. There is no point in having physicians if they do
      not have safe and ethical conditions to establish the diagnosis and a treatment
      plan, as well as to monitor the rehabilitation of the patient.

PMID- 28489135
TI  - Accuracy of ultrasound to detect thrombosis in pregnancy: A systematic review.
AB  - Objective: : To determine the diagnostic accuracy of ultrasound to detect deep-
      vein thrombosis in pregnant patients. Method:: We searched Pubmed, LILACS,
      Scopus, Google Scholar and System for Information on Grey Literature from
      inception to April 2016. The reference lists of the included studies were
      analyzed. Original articles from accuracy studies that analyzed ultrasonography
      to diagnose deep-vein thrombosis in pregnant women were included. Reference
      standard was the follow-up time. The QUADAS-2 score was used for quality
      assessment. Results:: Titles and summaries from 2,129 articles were identified.
      Four studies that evaluated deep-vein thrombosis in pregnant women were included.
      In all, 486 participants were enrolled. High risk of bias was seen in three out
      of four studies included regarding flow and timing domain of QUADAS-2. Negative
      predictive value was 99.39%. Conclusion:: Accuracy of ultrasonography to diagnose
      deep-vein thrombosis in pregnant women was not determined due to the absence of
      data yielding positive results. Further studies of low risk of bias are needed to
      determine the diagnostic accuracy of ultrasonography in this clinical scenario.

PMID- 28489136
TI  - Hyperferritinemia in patients with nonalcoholic fatty liver disease.
AB  - Objective: : In liver diseases, hyperferritinemia (HYF) is related to injured
      cells in acquired and genetic conditions with or without iron overload. It is
      frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it
      is necessary to define the mean of HYF to establish the better approach for them.
      The present study evaluated the significance of elevated ferritin in patients
      with NAFLD and steatohepatitis (NASH). Method:: The review was performed using
      search instruments of indexed scientific material, including MEDLINE (by PubMed),
      Web of Science, IBECS and LILACS, to identify articles published in Portuguese,
      English and Spanish, from 2005 to May, 2016. Studies eligible included place and
      year of publication, diagnose criteria to NAFLD, specifications of serum ferritin
      measurements and/or liver histopathologic study. Exclusion criteria included
      studies with patients with alcohol consumption >= 20 g/day and other liver
      diseases. Results:: A total of 11 from 30 articles were selected. It included
      3,564 patients and they were cross-sectional, retrospective, case series and case
      control. The result's analyses showed in 10 of these studies a relationship
      between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis
      and insulin resistance. Conclusion:: Hyperferritinemia in patients with
      NAFLD/NASH is associated more frequently with hepatocellular injury than
      hemochromatosis. These data suggest the relevance to evaluate carefully HYF in
      patients with NAFLD/NASH to establish appropriate clinical approach.

PMID- 28489137
TI  - New light on executive function and attention deficit hyperactivity disorder.

PMID- 28489138
TI  - Attention-deficit/hyperactivity disorder: the impact of methylphenidate on
      working memory, inhibition capacity and mental flexibility.
AB  - Objective: To compare children with attention-deficit/hyperactivity disorder
      (ADHD), before and after the use of methylphenidate, and a control group, using
      tests of working memory, inhibition capacity and mental flexibility. Methods:
      Neuropsychological tests were administrated to 53 boys, 9-12 years old: the WISC
      III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests.
      The case group included 23 boys with ADHD, who were combined type, treatment
      naive, and with normal intelligence without comorbidities. The control group (n =
      30) were age and gender matched. After three months on methylphenidate, the ADHD
      children were retested. The control group was also retested after three months.
      Results: Before treatment, ADHD children had lower scores than the control group
      on the tests (p <= 0.001) and after methylphenidate had fewer test errors than
      before (p <= 0.001). Conclusion: Methylphenidate treatment improves the working
      memory, inhibitory control and mental flexibility of ADHD boys.

PMID- 28489139
TI  - High expression of anti-apoptotic genes in grade I and II meningiomas.
AB  - Objective: To evaluate the expression of c-FLIP, XIAP, Bcl-2, caspase 3, 8 and 9,
      cytochrome c, APAF 1 and Smac/DIABLO genes related to apoptosis pathways.
      Methods: The gene expression was evaluated in 30 meningiomas (WHO grades I and
      II) and in 10 normal samples (from arachnoid tissue) through PCR-RT. Results: The
      results showed higher expression of anti-apoptotic genes in meningiomas when
      compared to the control group, which had a low expression of pro-apoptotic genes.
      Conclusion: There is a possible block in the activation of caspases through the
      intrinsic apoptosis pathway in meningiomas. c-FLIP modulates caspase 8 and, by
      inhibiting its activation due to the lack of connection with the receiver, there
      is a block to the FAS activation of apoptosis by its extrinsic pathway.

PMID- 28489140
TI  - Different outcomes of phonemic verbal fluency in Parkinson's disease patients
      with subthalamic nucleus deep brain stimulation.
AB  - Subthalamic nucleus deep brain stimulation (STN-DBS) is a surgical technique to
      treat motor symptoms in patients with Parkinson's disease (PD). Studies have
      shown that STN-DBS may cause a decline in verbal fluency performance. We aimed to
      verify the effects of STN-DBS on the performance of phonemic verbal fluency in
      Brazilian PD patients. Sixteen participants were evaluated on the Unified
      Parkinson's Disease Rating Scale - Part III and for phonemic fluency ("FAS"
      version) in the conditions of on- and off-stimulation. We identified two
      different patterns of phonemic verbal fluency outcomes. The results indicate that
      there may be no expected pattern of effect of bilateral STN-DBS in the phonemic
      fluency, and patients may present with different outcomes for some reason not
      well understood.

PMID- 28489141
TI  - Home-based exercise program in TSP/HAM individuals: a feasibility and
      effectiveness study.
AB  - Objective: To investigate the feasibility and effectiveness of a home-based
      exercise program in TSP/HAM individuals. Methods: Twenty-three TSP/HAM
      individuals divided in two groups according to Timed Up and Go (TUG) score (<20s
      vs >=20s) performed a 20-week home-based exercise program. The primary outcomes
      were exercise adherence, maximum voluntary isometric contraction of lower limbs
      (MVIC), Barthel Index and SF-36. Secondary outcomes were adverse effects and
      barriers to exercise practice. Results: MVIC and the social functioning domain in
      SF-36 improved significantly in TUG <20s group. The individuals in the TUG >=20s
      group improved significantly their physical functioning domain in SF-36. The
      total adherence to the 20-week home-based exercise program was 90%. There were
      mild to moderate adverse events related to exercise program. There were no
      adverse events related to MVIC test. Conclusions: The home-based exercise program
      was feasible and effective in improving disability and quality of life in
      individuals with TSP/HAM.

PMID- 28489142
TI  - Cognitive cooperation groups mediated by computers and internet present
      significant improvement of cognitive status in older adults with memory
      complaints: a controlled prospective study.
AB  - Objective: To estimate the effect of participating in cognitive cooperation
      groups, mediated by computers and the internet, on the Mini-Mental State
      Examination (MMSE) percent variation of outpatients with memory complaints
      attending two memory clinics. Methods: A prospective controlled intervention
      study carried out from 2006 to 2013 with 293 elders. The intervention group (n =
      160) attended a cognitive cooperation group (20 sessions of 1.5 hours each). The
      control group (n = 133) received routine medical care. Outcome was the percent
      variation in the MMSE. Control variables included gender, age, marital status,
      schooling, hypertension, diabetes, dyslipidaemia, hypothyroidism, depression,
      vascular diseases, polymedication, use of benzodiazepines, exposure to tobacco,
      sedentary lifestyle, obesity and functional capacity. The final model was
      obtained by multivariate linear regression. Results: The intervention group
      obtained an independent positive variation of 24.39% (CI 95% = 14.86/33.91) in
      the MMSE compared to the control group. Conclusion: The results suggested that
      cognitive cooperation groups, mediated by computers and the internet, are
      associated with cognitive status improvement of older adults in memory clinics.

PMID- 28489143
TI  - The use of a formula-based ketogenic diet in children with refractory epilepsy.
AB  - The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for
      refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and
      restricted protein diet, which is calculated and weighed for each individual
      patient. Introducing and maintaining the diet for a long time remains a
      challenge. In this study, we evaluated the acceptability, tolerance, and efficacy
      of a formula-based KD in 10 children with refractory epilepsy. The ketogenic
      formula tested herein caused only mild KD-related adverse events and adequate
      adherence. Moreover, 60% of patients had more than 50% seizure frequency
      reduction and 10% were seizure-free.

PMID- 28489144
TI  - Modified simple decompression in the treatment of cubital tunnel syndrome:
      avoiding ulnar nerve subluxation.
AB  - Objective: In this study, we propose a modification to the simple decompression
      technique that contains the ulnar nerve in the cubital fossa, thus preventing
      subluxation during forearm flexion movements. Methods: Five consecutive patients
      with leprosy-associated cubital tunnel syndrome underwent surgery with the
      modified technique between July 2011 and October 2012. Results: The most common
      symptoms were neuropathic pain and sensory changes (both 60%). On the McGowan
      scale, three patients maintained their preoperative score and two patients
      improved by two points, while on the Louisiana State University Health Sciences
      Center scale, two patients maintained the same scores, two improved by two
      points, and one improved by one point. Four patients were able to discontinue
      corticosteroid use. The mean follow-up time was 25.6 months (range 2-48 months).
      There were no recurrences or subluxations in the long-term. Conclusion: This
      alternative technique resulted in excellent functional results, as well as
      successful withdrawal from corticosteroids. Furthermore, it resulted in no ulnar
      nerve subluxations.

PMID- 28489145
TI  - Mismatch between diagnostic reports and special educational needs classification
      in a public educational system.
AB  - Objective: To assess the diagnostic status, the sociodemographic and health
      profiles for students with special educational needs (SEN) in a public
      educational system, and to map their use of educational/social services. Methods:
      The sample comprised 1,202 SEN students from a total of 59,344 students. Results:
      Only 792 students of the 1,202 had an established diagnosis. The most prevalent
      SEN condition was intellectual disability. There was a low percentage (29.4%) of
      use of specialized educational services or support. It was found that, for some
      neurodevelopmental disorders, prevalence data suggest an under-reporting in the
      school system. Conclusion: Results suggest that there is a mismatch between the
      diagnostic reports and the SEN condition legally recognized according to
      Brazilian law, in addition to the under-reporting and under specialized service
      use of students with disabilities.

PMID- 28489146
TI  - Acute muscular weakness in children.
AB  - Acute muscle weakness in children is a pediatric emergency. During the diagnostic
      approach, it is crucial to obtain a detailed case history, including: onset of
      weakness, history of associated febrile states, ingestion of toxic
      substances/toxins, immunizations, and family history. Neurological examination
      must be meticulous as well. In this review, we describe the most common diseases
      related to acute muscle weakness, grouped into the site of origin (from the upper
      motor neuron to the motor unit). Early detection of hyperCKemia may lead to a
      myositis diagnosis, and hypokalemia points to the diagnosis of periodic
      paralysis. Ophthalmoparesis, ptosis and bulbar signs are suggestive of myasthenia
      gravis or botulism. Distal weakness and hyporeflexia are clinical features of
      Guillain-Barre syndrome, the most frequent cause of acute muscle weakness. If all
      studies are normal, a psychogenic cause should be considered. Finding the
      etiology of acute muscle weakness is essential to execute treatment in a timely
      manner, improving the prognosis of affected children.

PMID- 28489147
TI  - Professor Wadia's contributions to neurology and spinocerebellar ataxia type 2.
AB  - The authors present a historical review of the seminal contributions of Professor
      N. H. Wadia (1925-2016) to neurology, in particular, the first description of
      spinocerebellar ataxia type 2.

PMID- 28489148
TI  - Incidental detection of probable meningioma in brain scintigraphy using 99mTc
      TRODAT-1.

PMID- 28489149
TI  - Frontal lobes white matter abnormalities mimicking cystic leukodystrophy in
      Wilson's disease.

PMID- 28489150
TI  - Bing-Neel syndrome.

PMID- 28489151
TI  - Erratum.
AB  - [This corrects the article doi: 10.1590/0004-282X20160157] [This corrects the
      article doi: 10.1590/0004-282x20160147] [This corrects the article doi:
      10.1590/0004-282X20160052].

PMID- 28489152
TI  - Evaluation of computer-generated guidelines for companions of paediatric patients
      undergoing chemotherapy.
AB  - Objective: To compare computer-generated guidelines with and without the use of a
      Clinical Decision Support System - Oncology Care and Healthcare for Chemotherapy
      Patients, for the caregivers of children undergoing chemotherapy. Methods: This
      is a descriptive, evaluative, and quantitative study conducted at a paediatrics
      hospital in Curitiba, Parana, Brazil, from December 2015 to January 2016. The
      sample consisted of 58 participants divided into two groups: Group 1, without the
      aid of software, and Group 2, with the aid of the software. The data were
      analysed using the Mann-Whitney U test. Results: The guidelines revealed a
      statistical significance (p<0.05), with a prevalence of a higher concordance
      average in Group 2 in comparison with Group 1. Conclusion: Computer-generated
      guidelines are a valuable qualitative support tool for nurses.

PMID- 28489153
TI  - Changes in nursing practice to improve patient safety.
AB  - Objective: To identify changes in nursing practice to improve the quality of care
      and patient safety. Method: A case study conducted at an inpatient unit with
      professionals from the patient safety centre and a nursing team, totalling 31
      participants. Data were collected from May to December 2015 through interviews,
      observations recorded in a field journal, and documentary analysis, followed by
      content analysis. Results: The changes observed in the nursing practice included
      the identification of care and physical risks, especially the risk of falls and
      pressure injury, with the use of personal forms and the Braden scale;
      notification of adverse events; adoption of protocols; effective communication
      with permanent education and multiprofessional meetings. Conclusions: Changes
      were observed in the nursing practice, chiefly focused on risk management.

PMID- 28489154
TI  - Serum positive thyroglobulin antibodies: an old problem with new questions.

PMID- 28489155
TI  - Subclinical carotid vascular disease and risk factors for atherosclerosis in type
      1 and type 2 diabetes.

PMID- 28489157
TI  - RESPECT TO HISTORY: VON PRESSER SYNDROME.

PMID- 28489156
TI  - Impact of free thyroxine levels and other clinical factors on bare metal stent
      restenosis.
AB  - Objective: Thyroid hormones have both direct and indirect effects on
      thermogenesis such as modulating vascular smooth muscle cell proliferation.
      However, the influence of more subtle changes in thyroid hormones on coronary
      atherosclerosis remains a matter of speculation. Smooth muscle cells play a
      crucial role in the pathogenesis of in-stent restenosis (ISR). However, the
      relationship between free thyroxine (fT4) and ISR has not been studied. In the
      present study, we aimed to assess the role of preprocedural serum fT4 level on
      the development of ISR in patients undergoing coronary bare metal stent (BMS)
      implantation. Materials and methods: We enrolled and analyzed clinical,
      biochemical, and angiographic data from 705 consecutive patients without a
      history of primary thyroid disease [mean age 60.3 +/- 9.3 years, 505 (72%) male];
      all patients had undergone BMS implantation and further control coronary
      angiography owing to stable or unstable angina pectoris. Patients were divided
      into 3 tertiles based on preprocedural serum fT4 levels. Results: ISR was
      observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the
      second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001).
      Using multiple logistic regression analysis, five characteristics emerged as
      independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent
      length, and preprocedural serum fT4 level. In receiver operating characteristics
      curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity
      (AUC: 0.75, p < 0.001) in predicting ISR. Conclusion: Higher preprocedural serum
      fT4 is a powerful and independent predictor of BMS restenosis in patients with
      stable and unstable angina pectoris.

PMID- 28489158
TI  - PREVALENCE AND PREDICTORS OF CHANGES IN BOWEL HABITS AFTER LAPAROSCOPIC
      CHOLECYSTECTOMY.
AB  - Background:: The incidence of cholecystolithiasis is approximately 15% of the
      population. It is believed that between 30-40% of cholecystectomy patients have
      symptoms after surgery, being changes in bowel habits the most common among them.
      Aim:: 1) Defining the prevalence, and 2) identifying predictors of changes in
      bowel habits after laparoscopic cholecystectomy. Methods:: This is a
      retrospective cross-sectional study with an initial sample of 150 patients
      diagnosed with cholecystolithiasis operated between July and September 2014.
      Patients were submitted to a questionnaire about the presence of gastrointestinal
      symptoms and changes in stools consistency before and after the surgical
      procedure. They were divided into two groups (with or without changes in bowel
      habits) being combined with the following variables: high blood pressure, body
      mass index, hypothyroidism, adherence to postoperative dietary orientations,
      previous abdominal and bariatric surgery. Results:: The prevalence of changes in
      bowel habits in the study population was 35.1%. The association between it and
      gastrointestinal symptoms was demonstrated to be statistically significant
      (0/002=7.981; p=0.005), and people who did not have gastrointestinal symptoms had
      2.34 times the odds of not presenting changes in bowel habits. None of the other
      investigated factors had shown to be a predictor of risk for post-cholecystectomy
      changes in bowel habits. Conclusion:: 1) There was a high prevalence of changes
      in bowel habits, and 2) there was association between changes in bowel habits and
      the presence of gastrointestinal symptoms. Racional:: A incidencia da
      colecistopatia calculosa e de aproximadamente 15% da populacao brasileira.
      Acredita-se que entre 30-40% dos pacientes colecistectomizados apresentem
      sintomas pos-operatorio, sendo a alteracao do habito intestinal o mais comum.
      Objetivo:: 1) Determinar a prevalencia, e 2) identificar preditores de mudancas
      do habito intestinal pos-colecistectomia videolaparoscopica. Metodos:: Estudo
      transversal retrospectivo com amostra inicial de 150 pacientes diagnosticados com
      colecistopatia calculosa, operados entre julho e setembro de 2014. Os pacientes
      foram submetidos a um questionario sobre a presenca de sintomas gastrointestinais
      apos a operacao, e a alteracoes do aspecto das fezes antes e depois do
      procedimento. A amostra foi dividida em dois grupos (com ou sem mudancas do
      habito intestinal) sendo realizadas associacoes com as seguintes variaveis:
      hipertensao arterial, IMC, hipotireoidismo, seguimento de dieta no pos
      operatorio, operacao abdominal previa e operacao bariatrica. Resultados:: A
      prevalencia de mudancas do habito intestinal na populacao estudada foi de 35,1%.
      A associacao entre elas e sintomas gastrointestinais demonstrou-se
      estatisticamente significativa (0/002=7,981; p=0,005), sendo que as pessoas que
      nao apresentavam os sintomas tinham 2,34 vezes mais chances de nao apresentarem
      mudancas do habito intestinal. Nenhum dos demais fatores investigados demonstrou
      ser preditor de risco para mudancas do habito intestinal pos-colecistectomia.
      Conclusoes:: 1) Observou-se alta prevalencia de mudancas do habito intestinal, e
      2) houve associacao entre mudanca do habito intestinal e a presenca de sintomas
      gastrointestinais.

PMID- 28489160
TI  - NUTRITIONAL ASPECTS AND THE USE OF NUTRITIONAL SUPPLEMENTS BY WOMEN WHO UNDERWENT
      GASTRIC BYPASS.
AB  - Background: Bariatric surgery is deemed one of the most effective procedures for
      the treatment of obesity and it aims at the reduction and maintenance of weight
      loss in long term, as the control of the related comorbidities. Aim: Quantify the
      occurrence of alterations of the gastrointestinal tract, suggestive signs of
      nutritional deficiencies and the use of supplements in a group of women
      undergoing bariatric surgery. Methods: The sample consisted of women aged 20-65
      years submitted to Roux-en-Y gastric bypass with monitoring equal to or higher
      than 24 months. For the qualitative analysis, the Feeding Frequency Questionnaire
      was used. Results: In the postoperative period, alopecia was the most reported
      (79.3%), followed by changes in the texture of the nails, both considered
      predictive of nutritional deficiencies. Changes in the gastrointestinal tract
      were described in 86.2%, and episodes of dumping were reported in 65.5%.
      Qualitative analysis has shown reduced daily consumption of sources of animal and
      plant proteins. Conclusion: After bariatric surgery can occur flatulence,
      vomiting and dumping syndrome as the most frequent representative symptoms of
      digestive functional disorders. Alopecia and nail changes are the most important
      signs of nutritional deficiency. The use of dietary supplements in the
      postoperative period is scarce and sporadic.

PMID- 28489159
TI  - CHANGING PARADIGMS IN PREOPERATIVE FASTING: RESULTS OF A JOINT EFFORT IN
      PEDIATRIC SURGERY.
AB  - Background:: Current researches associate long fasting periods to several adverse
      consequences. The fasting abbreviation to 2 h to clear liquids associated with
      the use of drinks containing carbohydrates attenuates endocrinometabolic response
      to surgical trauma, but often is observed children advised to not intake food
      from 00:00 h till the scheduled surgical time, regardless of what it is. Aim:: To
      evaluate the safety of a protocol of preoperative fasting abbreviation with a
      beverage containing carbohydrates, and early postoperative feeding in children
      underwent elective small/mid-size surgical procedures during a national task
      force on pediatric surgery. Methods:: Thirty-six patients were prospectively
      included, and for several reasons five were excluded. All 31 who remained in the
      study received a nutritional supplement containing 150 ml of water plus 12.5%
      maltodextrin 2 h before the procedure. Data of the pre-operative fasting time,
      anesthetic complications and time of postoperative refeeding, were collected.
      Results:: Twenty-three (74.2%) were males, the median age was 5 y, and the median
      weight was 20 kg. The median time of pre-operative fasting was 145 min and the
      time of post-operative refeeding was 135 min. There were no adverse effects on
      the anesthetic procedures or during surgery. Post-operatively, two children
      (6.5%) vomited. Conclusion:: The abbreviation of pre-operative fasting to 2 h
      with beverage containing carbohydrate in pediatric surgery is safe. Early
      refeeding in elective small/mid-size procedures can be prescribed. Racional::
      Trabalhos atuais associam longos periodos de jejum com diversas consequencias
      adversas. A abreviacao do jejum de 2 h para liquidos claros associado ao uso de
      bebidas contendo carboidratos atenua resposta endocrinometabolica ao trauma,
      porem frequentemente as criancas sao orientadas a nao ingerir alimentos a partir
      das 00:00 h do dia anterior a operacao, independente do horario do procedimento
      cirurgico. Objetivo:: Avaliar a seguranca de um protocolo de abreviacao do jejum
      pre-operatorio, com o uso de bebida contendo carboidratos, e realimentacao
      precoce. Metodos:: Foram avaliados prospectivamente 36 criancas submetidas a
      procedimentos cirurgicos eletivos de pequeno e medio porte. Cinco foram
      posteriormente excluidos do estudo. Todos os 31 remanescentes receberam
      suplemento nutricional com maltodextrina 12,5% em 150 ml de agua aproximadamente
      2 h antes do procedimento. Foram coletados dados do tempo de jejum pre
      operatorio, complicacoes anestesicas e tempo de realimentacao. Resultados:: Vinte
      e tres (74,2%) eram do genero masculino, com idade mediana de cinco anos e peso
      mediano de 20 kg. O tempo mediano de jejum pre-operatorio foi de 145 min e o
      tempo mediano para realimentacao foi de 135 min. Nao houve eventos adversos
      durante a anestesia ou operacao. No periodo pos-operatorio, duas (6,5%) criancas
      vomitaram. Conclusao:: A abreviacao de jejum pre-operatorio para 2 h com uso de
      bebida contendo carboidratos, em operacoes eletivas de criancas, e seguro e nao
      esta associado ao maior risco de broncoaspiracao pulmonar. Realimentacao precoce
      pode ser prescrita nos procedimentos cirurgicos analisados.

PMID- 28489161
TI  - QUALITY OF LIFE AFTER VERTICAL GASTRECTOMY EVALUATED BY THE BAROS QUESTIONNAIRE.
AB  - Background: The satisfactory outcome in the surgical treatment of obesity must
      include, in addition to weight loss, a significant change in the pre-existing
      comorbidities and in the quality of life. Aim: To evaluate the quality of life in
      the late postoperative period in patients that underwent videolaparoscopic sleeve
      gastrectomy. Methods: It was applied the questionnaire "Bariatric Analysis and
      Reporting Outcome System" (BAROS) in patients that underwent videolaparoscopic
      sleeve gastrectomy. Results: A total of 47 patients between 21-60 years old were
      evaluated. The total mean of BMI before surgery was 43.06+/-5.87 kg/m2. The
      average percentage of the reduction of excess weight after surgery was 85.46+/
      23.6%. The score obtained by patients in the questionnaire about the improvement
      in the quality of life showed excellent (36.17%), very good (40.43%), good
      (21.28%) and reasonable (2.13%) results. There was clinical improvement after
      surgery in all comorbidities investigated. Conclusion: The weight loss was
      critical to improve the quality of life and offered the resolution or clinical
      improvement in all of the investigated comorbidities in patients submitted to
      sleeve gastrectomy.

PMID- 28489162
TI  - ENDOSCOPIC SLEEVE GASTROPLASTY FOR OBESITY TREATMENT: TWO YEARS OF EXPERIENCE.
AB  - Background: Bariatric endoscopic techniques are minimally invasive and induce
      gastric volume reduction to treat obesity. Aim : To evaluate endoscopic sleeve
      gastroplasty (Apollo method) using a suturing method directed at the greater
      curvature, as well as the perioperative care, two year safety and weight loss.
      Method: Prospective single-center study over 154 patients (108 females) using the
      endoscopic sleeve gastroplasty procedure under general anesthesia with overnight
      inpatient observation. Of the154 initial patients, 143 were available for 1-month
      of follow-up, 133 for 6-month, 64 for 12-month and 28 completed the 24 month
      assessment. Follow-up was carried out by a multidisciplinary team (nutritionist
      and psychologist). Outcomes evaluated were: change in BMI; change in body weight
      (TBWL); % of loss of initial body weight (%TBWL); % of excess body weight loss
      (%EWL) (segregated in > or <25% and adverse effects. Voluntary oral contrasted
      radiological examinations were scheduled to assess the gastroplasty at different
      times post-procedure. Results: Mean age was 44.9 (23-69) years. At 24 months
      after the procedure baseline mean BMI change from 38.3 to 30.8 kg/m2. TBWL, %TBWL
      and %EWL were of 21.3 kg, 19.5% and 60.4% respectively. 85.7% of patients achieve
      the goal of >25% %EWL. There were no mayor adverse events intraprocedure or
      during the 24 months of follow-up . Conclusion: Endoscopic sleeve gastroplasty
      with regular monitoring by a multidisciplinary team can be considered an
      effective, safe and well tolerated procedure for obesity treatment, at least for
      two years of follow-up.

PMID- 28489163
TI  - HYPERVASCULAR LIVER LESIONS IN RADIOLOGICALLY NORMAL LIVER.
AB  - Background: The hypervascular liver lesions represent a diagnostic challenge.
      Aim: To identify risk factors for cancer in patients with non-hemangiomatous
      hypervascular hepatic lesions in radiologically normal liver. Method: This
      prospective study included patients with hypervascular liver lesions in
      radiologically normal liver. The diagnosis was made by biopsy or was presumed on
      the basis of radiologic stability in follow-up period of one year. Cirrhosis or
      patients with typical imaging characteristics of haemangioma were excluded.
      Results: Eighty-eight patients were included. The average age was 42.4. The
      lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy
      was performed in approximately 1/3 of cases. The lesions were benign or most
      likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate
      analysis showed that age >45 years (p< 0.001), personal history of cancer
      (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase
      (p=0.013) were significant risk factors for cancer. Conclusion: It is safe to
      observe hypervascular liver lesions in normal liver in patients up to 45 years,
      normal alanine aminotransaminase, up to three nodules and no personal history of
      cancer. Lesion biopsies are safe in patients with atypical lesions and define the
      treatment to be established for most of these patients.

PMID- 28489164
TI  - DIFFERENT PROTOCOLS OF POSTCONDITIONING DOES NOT ATTENUATE MESENTERIC ISCHEMIA
      REPERFUSION INJURY AFTER SHORT-TERM REPERFUSION.
AB  - Background: Mesenteric ischemia is a challenging diagnosis. Delay in diagnosis
      can lead to extent bowel necrosis and poor outcomes. Ischemia and reperfusion
      syndrome plays an important role in this scenario. Aim: To access effects of
      different post-conditioning cycles on mesenteric ischemia-reperfusion syndrome.
      Method: Twenty-five rats were assigned into five groups: Sham, used to establish
      normal parameters; control group, submitted to mesenteric ischemia for 30 min; in
      groups GP3, GP1 and GP30, ischemia was followed by post-conditioning protocol,
      which consisted of 1 cycle of 3 min (GP3), 3 cycles of 1 min (GP1) or 6 cycles of
      30 s (GP30), respectively. Ileum samples were harvested after one hour of
      reperfusion. Intestinal mucosal injury was evaluated through histopathological
      analysis. Results: The average of mesenteric injury degree was 0 in the sham
      group, 3.6 in the control group, 3.4 in GP3, 3.2 in GP1, and 3.0 in GP30; villous
      length average was 161.59 in sham group, 136.27 in control group, 135.89 in GP3,
      129.46 in GP1, and 135.18 in GP30. Was found significant difference between sham
      and other groups (p<0.05); however, there was no difference among post
      conditioning groups. Conclusion: Post-conditioning adopted protocols were not
      able to protect intestinal mucosa integrity after mesenteric ischemia and short
      term reperfusion.

PMID- 28489165
TI  - DETECTION OF OCCULT LYMPH NODE TUMOR CELLS IN NODE-NEGATIVE GASTRIC CANCER
      PATIENTS.
AB  - Background: The presence of lymph nodes metastasis is one of the most important
      prognostic indicators in gastric cancer. The micrometastases have been studied as
      prognostic factor in gastric cancer, which are related to decrease overall
      survival and increased risk of recurrence. However, their identification is
      limited by conventional methodology, since they can be overlooked after routine
      staining. Aim: To investigate the presence of occult tumor cells using
      cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically
      lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to
      a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The
      results for metastases, micrometastases and isolated tumor cells were also
      associated to clinicopathological characteristics and their impact on stage
      grouping. Tumor deposits within lymph nodes were defined according to the tumor
      node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were
      obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in
      24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single
      or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006)
      and perineural invasions (p=0.04), as well as peritumoral lymphocytic response
      (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally
      negative lymph nodes by H&E. The histologic stage of two patients was upstaged
      from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three
      among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion:
      The CK-immunostaining is an effective method for detecting occult tumor cells in
      lymph nodes and may be recommended to precisely determine tumor stage. It may be
      useful as supplement to H&E routine to provide better pathological staging.

PMID- 28489166
TI  - ANATOMIC VARIATIONS OF HEPATIC ARTERY: A STUDY IN 479 LIVER TRANSPLANTATIONS.
AB  - Background:: The incidence of anatomic variations of hepatic artery ranges from
      20-50% in different series. Variations are especially important in the context of
      liver orthotopic transplantation, since, besides being an ideal opportunity for
      surgical anatomical study, their precise identification is crucial to the success
      of the procedure. Aim:: To identify the anatomical variations in the hepatic
      arterial system in hepatic transplantation. Methods:: 479 medical records of
      transplanted adult patients in the 13-year period were retrospectively analyzed,
      and collected data on hepatic arterial anatomy of the deceased donor. Results::
      It was identified normal hepatic arterial anatomy in 416 donors (86.84%). The
      other 63 patients (13.15%) showed some variation. According to the Michels
      classification, the most frequently observed abnormalities were: right hepatic
      artery branch of superior mesenteric artery (Type III, n=27, 5.63%); left hepatic
      artery branch of the left gastric artery (Type II, n=13, 2.71%); right hepatic
      artery arising from the superior mesenteric artery associated with the left
      hepatic artery arising from the left gastric artery (Type IV, n=4, 0.83%).
      Similarly, in relation to Hiatt classification, the most prevalent changes were:
      right hepatic accessory artery or substitute of the superior mesenteric artery
      (Type III, n=28, 6.05%)), followed by liver ancillary left artery or replacement
      of gastric artery left (Type II, n=16, 3.34. Fourteen donors (2.92%) showed no
      anatomical abnormalities defined in classifications, the highest frequency being
      hepatomesenteric trunk identified in five (01.04%). Conclusion:: Detailed
      knowledge of the variations of hepatic arterial anatomy is of utmost importance
      to surgeons who perform approaches in this area, particularly in liver
      transplantation, since their identification and proper management are critical to
      the success of the procedure. Racional:: A incidencia das variacoes anatomicas da
      arteria hepatica varia de 20-50% em diferentes casuisticas. Elas sao
      especialmente importantes no contexto do transplante ortotopico hepatico, visto
      que, alem de representar oportunidade ideal para seu estudo anatomico cirurgico,
      a sua precisa identificacao e determinante para o sucesso do procedimento.
      Objetivo:: Identificar as variacoes anatomicas no sistema arterial hepatico em
      transplantes hepaticos. Metodo:: Foram analisados retrospectivamente, no periodo
      de 13 anos, 479 prontuarios de pacientes adultos transplantados, sendo coletados
      dados referentes a anatomia arterial hepatica do doador falecido. Resultados::
      Identificou-se anatomia arterial hepatica normal em 416 doadores (86,84%). Os
      outros 63 individuos (13,15%) apresentaram alguma variacao. De acordo com a
      classificacao de Michels, as anomalias mais frequentes foram: arteria hepatica
      direita ramo da arteria mesenterica superior (Tipo III, n=27, 5,63%); arteria
      hepatica esquerda ramo da arteria gastrica esquerda (Tipo II, n=13, 2,71%);
      arteria hepatica direita ramo da arteria mesenterica superior associada a arteria
      hepatica esquerda ramo da arteria gastrica esquerda (Tipo IV, n=4, 0,83%). Do
      mesmo modo, em relacao a Classificacao de Hiatt, as variacoes mais prevalentes
      foram: arteria hepatica direita acessoria ou substituta da arteria mesenterica
      superior (Tipo III, n=28, 6,05%), seguida da arteria hepatica esquerda acessoria
      ou substituta da arteria gastrica esquerda (Tipo II, n=16, 3,34%). Quatorze
      pessoas (2,92%) apresentaram alteracoes anatomicas sem classificacao definida,
      sendo a de maior frequencia o tronco hepatomesenterico, identificado em cinco
      (1,04%). Conclusao:: O conhecimento detalhado das variacoes da anatomia arterial
      hepatica e de grande importancia aos cirurgioes que realizam abordagens nessa
      regiao, em especial no transplante hepatico, visto que sua identificacao e
      correto manejo sao fundamentais para o exito do procedimento.

PMID- 28489167
TI  - PREOPERATIVE COMPUTED TOMOGRAPHY VOLUMETRY AND GRAFT WEIGHT ESTIMATION IN ADULT
      LIVING DONOR LIVER TRANSPLANTATION.
AB  - Background: Computed tomography volumetry (CTV) is a useful tool for predicting
      graft weights (GW) for living donor liver transplantation (LDLT). Few studies
      have examined the correlation between CTV and GW in normal liver parenchyma. Aim:
      To analyze the correlation between CTV and GW in an adult LDLT population and
      provide a systematic review of the existing mathematical models to calculate
      partial liver graft weight. Methods: Between January 2009 and January 2013, 28
      consecutive donors undergoing right hepatectomy for LDLT were retrospectively
      reviewed. All grafts were perfused with HTK solution. Estimated graft volume was
      estimated by CTV and these values were compared to the actual graft weight, which
      was measured after liver harvesting and perfusion. Results: Median actual GW was
      782.5 g, averaged 791.43+/-136 g and ranged from 520-1185 g. Median estimated
      graft volume was 927.5 ml, averaged 944.86+/-200.74 ml and ranged from 600-1477
      ml. Linear regression of estimated graft volume and actual GW was significantly
      linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation
      of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 
      0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients
      with normal liver parenchyma. A better estimation of graft weight could be
      reached by multiplying estimated graft volume by 0.82.

PMID- 28489169
TI  - MORTALITY OF URGENCY VERSUS ELECTIVE VIDEOLAPAROSCOPIC CHOLECYSTECTOMY FOR ACUTE
      CHOLECYSTITIS.
AB  - Background: Surgical approach is still controversial in patients with acute
      cholecystitis: to treat clinically the inflammatory process and operate
      electively later or to operate immediately on an emergency basis? Aim: To test
      the hypothesis that urgent laparoscopic cholecystectomy in acute cholecystitis
      has a higher mortality than elective laparoscopic cholecystectomy. Methods: From
      the data available in Datasus, mortality was compared between patients undergoing
      elective laparoscopic cholecystectomy for cholelithiasis and in urgency.
      Calculations were made of the relative reduction in risk of death, absolute
      reduction of risk of death and number needed to treat. Results: From 2009 to 2014
      in Brazil, there were 250.439 laparoscopic cholecystectomy and 74.6% were
      electives. Mortality in the emergency group was 4.8 times higher compared to the
      elective group (0.0023% vs. 0.00048%). Despite the relative reduction in risk of
      death (RRR) was 83%, in the calculation of absolute risk was found 0.0018 and
      number needed to treat of 55,555. Conclusions: Despite the relative risk
      reduction for mortality was high comparing elective vs. urgent basis, the
      absolute risk reduction was minimal, since this outcome is very low in both
      groups, suggesting that mortality should not have much influence on surgical
      decision.

PMID- 28489168
TI  - Angiolymphatic invasion as a prognostic fator in resected N0 pancreatic
      adenocarcinoma.
AB  - Background: Pancreatic adenocarcinoma remains one of the worst digestive cancers.
      Surgical resection is the main target when treating a patient with curative
      intent. Aim: To assess angiolymphatic invasion as a prognostic factor in resected
      pN0 pancreatic cancer. Methods: Thirty-eight patients were submitted to
      pancreatoduodenectomy due to head pancreatic cancer. Tumor size, margins, lymph
      nodes, pTNM staging, angiolymphatic and perineural invasion were described in the
      pathologists' reports. Results: Most patients were female. Overall median
      survival was 13 months. Gemcitabine was the regimen of choice for chemotherapy in
      selected patients; however, it did not improve overall survival. pR0 resection
      had better survival compared with pR1. Within the pN0 group, survival was
      significantly better in patients without angiolymphatic invasion. Conclusion:
      Angiolymphatic invasion in N0 pancreatoduodenectomy can be demonstrated by the
      Hematoxylin-Eosin stain and may predict a poor prognosis factor for those
      patients.

PMID- 28489170
TI  - MODIFIED ALVARADO SCORE IN CHILDREN WITH DIAGNOSIS OF APPENDICITIS.
AB  - Background: Appendicitis is one of the most common abdominal emergency. Some
      predictive scoring systems are recommended to decrease the rate of negative
      appendectomy. Aim: To evaluate sensitivity, specificity, positive predictive
      value, and negative predictive value of modified Alvarado score in children who
      underwent appendectomy. Methods: Four hundred children with initial diagnosis of
      appendicitis were randomly selected from patients who underwent appendectomy.
      Modified Alvarado score was used for evaluation of the appendicitis, that was
      confirmed using histology. Results: Of modified Alvarado score components,
      anorexia; nausea and vomiting and rebound tenderness were significantly more
      common in children with positive appendectomy in contrast to patients with
      negative appendectomy. Sensitivity, specificity, positive predictive value, and
      negative predictive value for modified Alvarado score were: 91.3%; 38.4%; 87.7%;
      and 51.2% respectively. Conclusion: Alvarado score has high sensitivity but low
      specificity for diagnosis of acute appendicitis in children.

PMID- 28489171
TI  - ALTERNATIVE TECHNIQUE FOR CHOLECYSTECTOMY COMPARABLE TO SINGLE PORT.
AB  - Background: With the advancement of laparoscopic surgery, new techniques have
      been proposed and disseminated in order to reduce the surgical aggression and get
      better cosmetic results. Aim: To present alternative technique for
      videocholecystectomy comparable to single port technique using conventional
      material for laparoscopic surgery. Method: Introduction of laparoscopic devices
      using two incisions; gallbladder traction with thread, exposition of Calot
      triangle, and ligature of cystic pedicle with polymer clips. Results: Nine
      operations were carried out with this method, without complications and no
      increase in operative time, being compared to conventional videocholecistectomy,
      however vastly superior in aesthetic results. Conclusion: The technique is
      feasible, reproducible, showing benefits to patient's safety.

PMID- 28489172
TI  - LAPAROSCOPIC REPAIR OF LUMBAR HERNIA (GRYNFELT): TECHNICAL DESCRIPTION.
AB  - Background:: Lumbar hernias are rare. Usually manifest with reducible volume
      increase in the post-lateral region of the abdomen and may occur in two specific
      anatomic defects: the triangles of Grynfelt (upper) and Petit (lower). Despite
      controversies with better repair, laparoscopic approach, following the same
      principle of the treatment of inguinal hernias, seems to present significant
      advantages compared to conventional/open surgeries. However, some technical and
      anatomical details of the region, non usual to general surgeons, are fundamental
      for proper repair. Aim:: To present systematization of laparoscopic
      transabdominal technique for repair of lumbar hernias with emphasis on anatomical
      details. Method: : Patient is placed in the lateral decubitus. Laparoscopic
      access to abdominal cavity is performed by open technique on the left flank, 1.5
      cm incision, followed by introduction of 11 mm trocar for a 30o scope. Two other
      5 mm trocars, in the left anterior axillary line, are inserted into the abdominal
      cavity. The peritoneum of the left paracolic gutter is incised from the 10th rib
      to the iliac crest. Peritoneum and retroperitoneal is dissected. Reduction of all
      hernia contents is performed to demonstrate the hernia and its size. A 10x10 cm
      polypropylene mesh is introduced into the retroperitoneal space and fixed with
      absorbable staples covering the defect with at least 3-4 cm overlap.
      Subsequently, is carried out the closure of the peritoneum of paracolic gutter.
      Results:: This technique was used in one patient with painful increased volume in
      the left lower back and bulging on the left lumbar region. CT scan was performed
      and revealed left superior lumbar hernia. Operative time was 45 min and there
      were no complications and hospitalization time of 24 h. Conclusion:: As in
      inguinal hernia repair, laparoscopic approach is safe and effective for the
      repair of lumbar hernias, especially if the anatomical details are adequately
      respected. Racional:: As hernias lombares sao raras. Geralmente se manifestam com
      aumento de volume redutivel na regiao postero-lateral do abdome e podem ocorrer
      em dois defeitos anatomicos especificos: os triangulos de Grynfelt (superior) e
      Petit (inferior). Apesar de controversias com relacao a melhor forma de reparo, a
      abordagem laparoscopica, seguindo o mesmo principio do tratamento das hernias
      inguinais, parece apresentar vantagens significativas em relacao as operacoes
      convencionais/abertas. Entretanto, alguns detalhes tecnicos e anatomicos desta
      regiao, nao usual aos cirurgioes gerais, sao fundamentais para o adequado reparo.
      Objetivo:: Apresentar sistematizacao da tecnica laparoscopica transabdominal para
      a correcao das hernias lombares com enfase nos detalhes anatomicos. Metodo::
      Paciente e colocado em decubito lateral. O acesso laparoscopico a cavidade
      abdominal e realizado pela tecnica aberta no flanco esquerdo, incisao de 1,5 cm,
      seguida pela introducao de trocarteres de 11 mm para otica de 30o. Dois outros
      trocarteres de 5 mm, na linha axilar anterior esquerda, sao inseridos na cavidade
      abdominal. O peritonio da goteira paracolica esquerda e incisado desde a 10a
      costela ate a crista iliaca. O peritonio e o retroperitoneal sao dissecados. A
      reducao de todo o conteudo de hernia e realizada para demonstrar a hernia e seu
      tamanho. Tela de polipropileno de 10x10 cm e introduzida no espaco
      retroperitoneal e fixada com grampos absorviveis cobrindo o defeito com pelo
      menos 3-4 cm de sobreposicao. Posteriormente, realiza-se o fechamento do
      peritonio da goteira paracolica. Resultados:: Esta tecnica foi utilizada em um
      paciente com aumento doloroso de volume na regiao lombar esquerda e abaulamento
      na regiao lombar esquerda. Tomografia computadorizada foi realizada e revelou
      hernia lombar superior esquerda. O tempo operatorio foi de 45 min e nao houve
      complicacoes; o tempo de hospitalizacao de 24 h. Conclusoes:: Assim como no
      reparo das hernias inguinais, a abordagem laparoscopica e segura e efetiva para
      as hernias lombares, especialmente se os detalhes anatomicos forem adequadamente
      respeitados.

PMID- 28489173
TI  - NEW TECHNIQUE FOR OBESITY SURGERY: INTERNAL GASTRIC PLICATION TECHNIQUE USING
      INTRAGASTRIC SINGLE-PORT (IGS-IGP) IN EXPERIMENTAL MODEL.
AB  - Background: : Bariatric surgery is currently the most effective method to
      ameliorate co-morbidities as consequence of morbidly obese patients with BMI over
      35 kg/m2. Endoscopic techniques have been developed to treat patients with mild
      obesity and ameliorate comorbidities, but endoscopic skills are needed, beside
      the costs of the devices. Aim:: To report a new technique for internal gastric
      plication using an intragastric single port device in an experimental swine
      model. Methods:: Twenty experiments using fresh pig cadaver stomachs in a
      laparoscopic trainer were performed. The procedure was performed as follow in ten
      pigs: 1) volume measure; 2) insufflation of the stomach with CO2; 3) extroversion
      of the stomach through the simulator and installation of the single port device
      (Gelpoint Applied Mini) through a gastrotomy close to the pylorus; 4) performance
      of four intragastric handsewn 4-point sutures with Prolene 2-0, from the gastric
      fundus to the antrum; 5) after the performance, the residual volume was measured.
      Sleeve gastrectomy was also performed in further ten pigs and pre- and post
      procedure gastric volume were measured. Results:: The internal gastric plication
      technique was performed successfully in the ten swine experiments. The mean
      procedure time was 27+/-4 min. It produced a reduction of gastric volume of a
      mean of 51%, and sleeve gastrectomy, a mean of 90% in this swine model.
      Conclusion:: The internal gastric plication technique using an intragastric
      single port device required few skills to perform, had low operative time and
      achieved good reduction (51%) of gastric volume in an in vitro experimental
      model. Racional:: A cirurgia bariatrica e atualmente o metodo mais efetivo para
      melhorar as co-morbidades decorrentes da obesidade morbida com IMC acima de 35
      kg/m2. Tecnicas endoscopicas foram desenvolvidas para tratar pacientes com
      obesidade leve e melhorar as comorbidades, mas habilidades endoscopicas sao
      necessarias, alem dos custos. Objetivo:: Relatar uma nova tecnica para a
      plicatura gastrica interna utilizando um dispositivo intragastrico de portal
      unico em modelo experimental de suinos. Metodos:: Foram realizados 20
      experimentos utilizando estomagos de cadaver de porco fresco em um instrutor
      laparoscopico. O procedimento foi realizado da seguinte forma em dez porcos: 1)
      medida de volume; 2) insuflacao do estomago com CO2; 3) extroversao do estomago
      atraves do simulador e instalacao do dispositivo de uma unica via (Gelpoint
      Applied Mini) atraves de uma gastrotomia proxima ao piloro; 4) realizacao de
      quatro suturas de quatro pontos intra-gastricas com Prolene 2-0, desde o fundo
      gastrico ate o antro; 5) medicao do volume residual. A gastrectomia vertical foi
      tambem realizada em mais dez suinos e o volume gastrico pre e pos-procedimento
      foi medido. Resultados:: A tecnica de plicatura gastrica interna foi realizada
      com sucesso nos dez experimentos com suinos. O tempo medio do procedimento foi de
      27+/-4 min. Produziu reducao do volume gastrico em media de 51%, e a gastrectomia
      vertical em media de 90% neste modelo suino. Conclusao:: A tecnica de plicatura
      gastrica interna, utilizando um dispositivo intragastrico de uma unica via,
      exigiu poucas habilidades para ser realizada, teve baixo tempo operatorio e
      obteve boa reducao (51%) do volume gastrico em um modelo experimental in vitro.

PMID- 28489174
TI  - THE IMPACT OF THE MELD SCORE ON LIVER TRANSPLANT ALLOCATION AND RESULTS: AN
      INTEGRATIVE REVIEW.
AB  - Introduction: Liver transplantation is intended to increase the survival of
      patients with chronic liver disease in terminal phase, as well as improved
      quality of life. Since the first transplant until today many changes have
      occurred in the organ allocation system. Objective: To review the literature on
      the Model for End-stage Liver Disease (MELD) and analyze its correlation with
      survival after liver transplantation. Method: An integrative literature review in
      Lilacs, SciELO, and Pubmed in October 2015, was realized. Were included eight
      studies related to the MELD score and its impact on liver transplant. Results:
      There was predominance of transplants in male between 45-55 y. The main
      indications were hepatitis C, hepatocellular carcinoma and alcoholic cirrhosis.
      The most important factors post-surgery were related to the MELD score, the
      recipient age, expanded donor criteria and hemotransfusion. Conclusion: The MELD
      system reduced the death rate in patients waiting for a liver transplant.
      However, this score by itself is not a good predictor of survival after liver
      transplantation.

PMID- 28489175
TI  - A PICTORIAL PRESENTATION OF ESOPHAGEAL HIGH RESOLUTION MANOMETRY CURRENT
      PARAMETERS.
AB  - Introduction:: High resolution manometry is the current technology used to the
      study of esophageal motility and is replacing conventional manometry in important
      centers for esophageal motility with parameters used on esophageal motility,
      following the Chicago Classification. This classification unifies high resolution
      manometry interpretation and classifies esophageal disorders. Objective:: This
      review shows, in a pictorial presentation, the new parameters established by the
      Chicago Classification, version 3.0, aimed to allow an easy comprehension and
      interpretation of high resolution manometry. Methods:: Esophageal manometries
      performed by the authors were reviewed to select illustrative tracings
      representing Chicago Classification parameters. Results:: The parameters are:
      Esophagogastric Morphology, that classifies this junction according to its
      physiology and anatomy; Integrated Relaxation Pressure, that measures the lower
      esophageal sphincter relaxation; Distal Contractile Integral, that evaluates the
      contraction vigor of each wave; and, Distal Latency, that measures the
      peristalsis velocity from the beginning of the swallow to the epiphrenic ampulla.
      Conclusion:: Clinical applications of these new concepts is still under
      evaluation. Objetivo:: Mostrar, de forma pictorica, os novos parametros
      compilados na versao 3.0 da Classificacao de Chicago, buscando facilitar a
      compreensao e interpretacao da manometria de alta resolucao. Metodos:: Foram
      revistas as manometrias da casuistica dos autores e selecionados os tracados
      representativos dos parametros da Classificacao de Chicago. Resultados:: Entre os
      parametros apresentados foram considerados a Morfologia da Transicao
      Gastroesofagica, que classifica o segmento de acordo com sua fisiologia e
      anatomia; a Integral da Pressao de Relaxamento, que mede o relaxamento do
      esfincter esofagiano inferior; a Integral Contratil Distal, que avalia o vigor
      contratil da onda peristaltica; e, a Latencia Distal, que mede o tempo da
      peristalse, desde o inicio da degluticao ate a ampola epifrenica. Conclusao:: A
      aplicabilidade clinica desses novos conceitos ainda esta sendo estudada.

PMID- 28489176
TI  - BRUNNER GLAND ADENOMA MASQUERADING AS DUODENAL GASTROINTESTINAL STROMAL TUMOR
      WITH INTUSSUSCEPTION: CASE REPORT.

PMID- 28489177
TI  - MANAGEMENT OF FLAP DEHISCENCE AFTER LiMBERG PROCEDURE FOR RECURRENT PiLONiDAL
      DiSEASE BY NEGATiVE PRESSURE WOUND THERAPY (NPWT).

PMID- 28489178
TI  - Blood pressure variability in the elderly. Association between postprandial and
      sleeping periods.
AB  - INTRODUCTION: The variability of arterial blood pressure (BP) is considered an
      important cardiovascular risk factor. OBJECTIVE: To verify the possible
      associations between the postprandial and the sleeping blood pressure
      variability. METHODS: This study evaluated systolic, diastolic, mean, pulse
      pressures and heart variability in 69 elderly patients in preprandial,
      postprandial and sleeping periods. One 24 hours ambulatory blood pressure
      monitoring was used for measurements and the results were showed in the time-rate
      index. RESULTS: We observed a decrease in the systolic blood pressure values from
      preprandial to postprandial and to the sleeping periods (124.7 +/- 14.6, 113.2 +/
      15.3 and 108.5 +/- 13.9mmHg, respectively; p = 0.003). Associations between BP
      variability of the postprandial and sleeping periods were obtained for systolic,
      diastolic and mean arterial pressure. CONCLUSION: The correlation between
      postprandial and sleeping BP variability has rarely been demonstrated in the
      literature. These correlations between BP changes after eating and during sleep
      might suggest that both events could coexist in other clinical situations.

PMID- 28489179
TI  - Analysis of economic impact between the modality of renal replacement therapy.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is a major health problem, determining
      the reduction in life expectancy and an increased risk of cardiovascular disease.
      METHOD: An observational, cohort, retrospective, based on patient's medical
      records data with CKD under hemodialysis, peritoneal dialysis and kidney
      transplantation in the city of Curitiba, in the period from January to June 2014,
      evacuativo the financial impact on the Unified Health System (SUS) and the
      supplementary health. RESULTS: The lowest cost of a kidney transplant in the
      first year was R$ 40,743.03 when cyclosporine was used and the highest was R$
      48,388.17 with the use of tacrolimus. In the second year post-transplant,
      hemodialysis and peritoneal dialysis have a higher cost compared to kidney
      transplant. Transplantation with deceased donor, treated with tacrolimus: R$
      67,023.39; Hemodialysis R$ 71,717.51 and automated peritoneal dialysis automatic
      R$ 69,527.03. CONCLUSIONS: After the first two years of renal replacement
      therapy, transplantation demonstrates lower costs to the system when compared to
      other modalities evaluated. Based on that, this therapy justifies improvements in
      government policies in this sector.

PMID- 28489180
TI  - Does infection by the hepatitis C virus decrease the response of immunization
      against the hepatitis B virus in individuals undergoing dialysis?
AB  - INTRODUCTION: Vaccination is the most effective tool in preventing transmission
      of Hepatitis B Virus (HBV). The patient with chronic kidney disease (CKD) on
      dialysis appear to be at greater risk of becoming infected with this virus and
      does not show the same vaccine response when compared to patients without uremia.
      OBJECTIVES: To evaluate the results related to the HBV vaccine and identify
      factors associated with the response in patients with CKD on hemodialysis.
      METHODS: Individuals with HBsAG and negative anti-HBC, under hemodialysis were
      assessed in two units of Sao Luis, Maranhao and were undergone full vaccination
      schedule for HBV. They were divided in groups: anti-HBs10 mUI/mL and compared as
      to age, gender, presence of diabetes mellitus (DM), time on dialysis and anti-HCV
      status. Logistic regression analysis was performed to identify factors
      independently associated with the vaccine response. p10mUI/Ml (or = 5.239 IC:
      1.279-21.459, p = 0.021). CONCLUSION: The rate of vaccine response to HBV in
      patients with CKD on dialysis was 70% and the lack of anti-HCV infection was
      associated with seroconversion of anti-HBs suggesting that infection by the
      hepatitis C virus may be a factor that decreases the response of the HBV vaccine
      in dialysis CKD patients.

PMID- 28489181
TI  - Early postoperative parathormone sampling and prognosis after total
      parathyroidectomy in secondary hyperparathyroidism.
AB  - INTRODUCTION: There is possibility of a supernumerary hyperplastic parathyroid
      gland in dialysis patients after total parathyroidectomy and autograft in
      dialysis patients. OBJECTIVE: To test if the early postoperative measure of
      parathyroid hormone (PTH) can identify persistent hyperparathyroidism. METHODS: A
      prospective cohort of dialysis patients submitted to parathyroidectomy had PTH
      measured up to one week after operation. The absolute value and the relative
      decrease were analyzed according to clinical outcome of satisfactory control of
      secondary hyperparathyroidism or persistence. RESULTS: Of 51 cases, preoperative
      PTH varied from 425 to 6,964 pg/mL (median 2,103 pg/mL). Postoperatively, PTH was
      undetectable in 28 cases (54.9%). In eight individuals (15.7%) the PTH was lower
      than 16 pg/mL, in 10 (19.6%) the PTH values were between 16 and 87pg/mL, and in
      five (9.8%), PTH was higher than 87 pg/mL. Undetectable PTH was more common in
      patients with preoperative PTH below the median (p = 0.0002). There was a
      significant correlation between preoperative PTH and early postoperative PTH
      (Spearman R = 0.42, p = 0.002). A relative decrease superior to 95% was
      associated to satisfactory clinical outcome. A relative decrease less than 80%
      was associated to persistent disease, despite initial postoperative hypocalcemia.
      CONCLUSION: Measurement of PTH in the first days after parathyroidectomy in
      dialysis patients may suggest good clinical outcome if a decrease of at least 95%
      of the preoperative value is observed. Less than 80% PTH decrease is highly
      suggestive of residual hyperfunctioning parathyroid tissue with persistent
      hyperparathyroidism, and an early reintervention may be considered.

PMID- 28489182
TI  - Acute effects of intradialytic aerobic exercise on solute removal, blood gases
      and oxidative stress in patients with chronic kidney disease.
AB  - INTRODUCTION: Hemodialysis contributes to increased oxidative stress and induces
      transitory hypoxemia. Compartmentalization decreases the supply of solutes to the
      dialyzer during treatment. The aim of this study was to investigate the acute
      effects of intradialytic aerobic exercise on solute removal, blood gases and
      oxidative stress in patients with chronic kidney disease during a single
      hemodialysis session. METHODS: Thirty patients were randomized to perform aerobic
      exercise with cycle ergometer for lower limbs during 30 minutes with intensity
      between 60-70% of maximal heart rate, or control group (CG). Blood samples were
      collected prior to and immediately after exercise or the equivalent time in CG.
      Analysis of blood and dialysate biochemistry as well as blood gases were
      performed. Mass removal and solute clearance were calculated. Oxidative stress
      was determined by lipid peroxidation and by the total antioxidant capacity.
      RESULTS: Serum concentrations of solutes increased with exercise, but only
      phosphorus showed a significant elevation (p = 0.035). There were no significant
      changes in solute removal and in the acid-base balance. Both oxygen partial
      pressure and saturation increased with exercise (p = 0.035 and p = 0.024,
      respectivelly), which did not occur in the CG. The total antioxidant capacity
      decreased significantly (p = 0.027). CONCLUSION: The acute intradialytic aerobic
      exercise increased phosphorus serum concentration and decreased total antioxidant
      capacity, reversing hypoxemia resulting from hemodialysis. The intradialytic
      exercise did not change the blood acid-base balance and the removal of solutes.

PMID- 28489183
TI  - Frequency and factors associated with falls in adults aged 55 years or more.
AB  - OBJECTIVE: The objective of this study is to analyze the frequency and factors
      associated with falls in adults aged 55 years or more. METHODS: This is a study
      inserted into another population-based study with representative sample of
      persons aged 40 years or more of the urban area in a medium-sized municipality of
      the State of Parana, Brazil, in 2011. That study obtained demographic and
      socioeconomic data and characteristics related to life habits, health conditions,
      and functional capacity (n = 1,180). In 2012, we selected all persons aged 55
      years or more (n = 501). We have estimated grip strength and the occurrence of a
      fall since the last interview in 80.6% of the adults. The crude and adjusted odds
      ratios (OR) have been calculated by logistic regression according to a
      hierarchical model. RESULTS: The rate of fall was 24.3%. After adjustments, we
      could observe higher chances of falls among women (OR = 3.10; 95%CI 1.79-5.38),
      among persons aged 65 years or more (OR = 2.39; 95%CI 1.45-3.95), with poor sleep
      quality (OR = 1.78; 95%CI 1.08-2.93), and with low grip strength (OR = 2.31;
      95%CI 1.34-3.97). CONCLUSIONS: Poor sleep quality and low muscle strength can be
      indicators of increased risk of falls and need assessments and interventions
      aimed at preventing them. OBJETIVO: Analisar a frequencia e fatores associados a
      ocorrencia de quedas em adultos de 55 anos ou mais. METODOS: Estudo inserido em
      outro de base populacional com amostra representativa de pessoas com 40 anos ou
      mais da area urbana de municipio de medio porte do Parana em 2011. Foram obtidos
      dados demograficos e socioeconomicos, caracteristicas referentes aos habitos de
      vida, as condicoes de saude e a capacidade funcional (n = 1.180). Em 2012,
      selecionaram-se todas as pessoas com idade igual ou superior a 55 anos (n = 501).
      Foram estimadas a forca de preensao palmar e a ocorrencia de queda desde a ultima
      entrevista em 80,6% delas. Foram calculadas odds ratios (OR) brutas e ajustadas
      por regressao logistica segundo modelo hierarquizado. RESULTADOS: A frequencia de
      queda foi de 24,3%. Apos ajustes, observaram-se chances maiores de queda entre
      mulheres (OR = 3,10; IC95% 1,79-5,38), entre pessoas com idade igual ou superior
      a 65 anos (OR = 2,39; IC95% 1,45-3,95), com qualidade do sono ruim (OR = 1,78;
      IC95% 1,08-2,93) e com baixa forca de preensao palmar (OR = 2,31; IC95% 1,34
      3,97). CONCLUSOES: Qualidade ruim do sono e a baixa forca muscular podem ser
      indicadores de maior risco de quedas e merecem avaliacoes e intervencoes visando
      a prevencao desse agravo.

PMID- 28489184
TI  - Hepatitis C among blood donors: cascade of care and predictors of loss to follow
      up.
AB  - OBJECTIVE: To investigate the HCV cascade of care and to identify the factors
      associated with loss or absence to follow-up of patients identified as infected
      with hepatitis C through blood donation. METHODS: Blood donors from 1994 to 2012,
      identified with positive anti- HCV by enzyme immunoassay and immunoblot tests
      were invited to participate in the study, through letters or phone calls.
      Patients who agreed to participate were interviewed and their blood samples were
      collected for further testing. The following variables were investigated:
      demographic data, data on comorbidities and history concerning monitoring of
      hepatitis C. Multiple regression analysis by Poisson regression model was used to
      investigate the factors associated with non-referral for consultation or loss of
      follow-up. RESULTS: Of the 2,952 HCV-infected blood donors, 22.8% agreed to
      participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian.
      Of the 676 participants, 39.7% did not receive proper follow-up or treatment
      after diagnosis: 45 patients referred not to be aware they were infected, 61 did
      not seek medical attention and 163 started a follow-up program, but were non
      adherent. The main reasons for inadequate follow-up were not understanding the
      need for medical care (71%) and health care access difficulties (14%). The
      variables showing a significant association with inadequate follow-up after
      multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15-1.71), age
      under or equal to 50 years (PR = 1.36; 95%CI 1.12-1.65) and non-Caucasians (PR =
      1.53; 95%CI 1.27-1.84). CONCLUSIONS: About 40.0% of patients did not receive
      appropriate follow-up. These data reinforce the need to establish strong links
      between primary care and reference centers and the need to improve access to
      specialists and treatments.

PMID- 28489185
TI  - Risk factors associated with multidrug-resistant tuberculosis in Espirito Santo,
      Brazil.
AB  - OBJECTIVE: To analyze the prevalence and factors associated with multidrug
      resistant tuberculosis in Espirito Santo, Brazil. METHODS: This is a cross
      sectional study of cases of tuberculosis tested for first-line drugs (isoniazid,
      rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espirito Santo between
      2002 and 2012. We have used laboratory data and registration of cases of
      tuberculosis - from the Sistema Nacional de Agravos de Notificacao and Sistema
      para Tratamentos Especiais de Tuberculose. Individuals have been classified as
      resistant and non-resistant and compared in relation to the sociodemographic,
      clinical, and epidemiological variables. Some variables have been included in a
      logistic regression model to establish the factors associated with resistance.
      RESULTS: In the study period, 1,669 individuals underwent anti-tuberculosis drug
      susceptibility testing. Of these individuals, 10.6% showed resistance to any anti
      tuberculosis drug. The rate of multidrug resistance observed, that is, to
      rifampicin and isoniazid, has been 5%. After multiple analysis, we have
      identified as independent factors associated with resistant tuberculosis: history
      of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24-14.05)
      and re-entry after abandonment (OR = 3.91; 95%CI 1.81-8.43)], smoking (OR = 3.93;
      95%CI 1.98-7.79), and positive culture for Mycobacterium tuberculosis at the time
      of notification of the case (OR = 3.22; 95%CI 1.15-8.99). CONCLUSIONS: The
      partnership between tuberculosis control programs and health teams working in the
      network of Primary Health Care needs to be strengthened. This would allow the
      identification and monitoring of individuals with a history of previous treatment
      of tuberculosis and smoking. Moreover, the expansion of the offer of the culture
      of tuberculosis and anti-tuberculosis drug susceptibility testing would provide
      greater diagnostic capacity for the resistant types in Espirito Santo. OBJETIVO:
      Analisar a prevalencia e fatores associados a tuberculose resistente no Espirito
      Santo. METODOS: Estudo transversal dos casos de tuberculose testados para
      farmacos de primeira linha (isoniazida, rifampicina, pirazinamida, etambutol e
      estreptomicina) no Espirito Santo entre 2002 e 2012. Foram utilizados dados
      laboratoriais e de registro de casos de tuberculose - Sistema Nacional de Agravos
      de Notificacao e Sistema para Tratamentos Especiais de Tuberculose. Os individuos
      foram classificados em resistentes e nao resistentes, e comparados para variaveis
      sociodemograficas, clinicas e epidemiologicas. Algumas variaveis foram inclusas
      em um modelo de regressao logistica para estabelecimento de fatores associados a
      resistencia. RESULTADOS: No periodo do estudo, 1.669 individuos tiveram o teste
      de sensibilidade aos farmacos antituberculose realizado. Destes, 10,6%
      apresentaram resistencia a qualquer droga antituberculose. A taxa de
      multirresistencia observada, isto e, a rifampicina e isoniazida, foi de 5%. Apos
      a analise multipla, foram identificados como fatores associados independentes
      para tuberculose resistente: historia de tratamento previo para tuberculose
      [Recidiva (OR = 7,72; IC95% 4,24-14,05) e reingresso apos abandono (OR = 3,91;
      IC95% 1,81-8,43)], tabagismo (OR = 3,93; IC95% 1,98-7,79) e cultura positiva para
      Mycobacterium tuberculosis no momento da notificacao do caso (OR = 3,22; IC95%
      1,15-8,99). CONCLUSOES: E necessario o fortalecimento da parceria entre os
      programas de controle de tuberculose e as equipes de saude que atuam na rede de
      Atencao Primaria a Saude. Isso possibilitaria identificar e acompanhar individuos
      com historia de tratamento previo para tuberculose e tabagismo. Alem disso, a
      ampliacao da oferta de cultura e Teste de Sensibilidade a farmacos
      antituberculose proporcionaria maior capacidade diagnostica para as formas
      resistentes no Espirito Santo.

PMID- 28489186
TI  - Overweight, obesity, steps, and moderate to vigorous physical activity in
      children.
AB  - OBJECTIVE: The objective of this study is to establish cutoff points for the
      number of steps/day and minutes/day of moderate to vigorous physical activity in
      relation to the risk of childhood overweight and obesity and their respective
      associations. In addition, we aim to identify the amount of steps/day needed to
      achieve the recommendation of moderate to vigorous physical activity in children
      from Sao Caetano do Sul. METHODS: In total, 494 children have used an
      accelerometer to monitor steps/day and the intensity of physical activity
      (min/day). The moderate to vigorous physical activity has been categorized
      according to the public health recommendation (<= 60 versus > 60 min/day).
      Overweight or obesity is defined as body mass index > +1 SD, based on reference
      data from the World Health Organization. The data on family income, education of
      parents, screen time, diet pattern, and sedentary time have been collected by
      questionnaires. Logistic regression and Receiver Operating Characteristic curves
      have been constructed. RESULTS: On average, boys walked more steps/day (1,850)
      and performed more min/day of moderate to vigorous physical activity (23.1) than
      girls. Overall, 51.4% of the children have been classified as eutrophic and 48.6%
      as overweight or obese. Eutrophic boys walked 1,525 steps/day and performed 18.6
      minutes/day more of moderate to vigorous physical activity than those with
      overweight/obesity (p < 0.05). The same has not been found in girls (p > 0.05).
      The cutoff points to prevent overweight and obesity in boys and girls were 10,500
      and 8,500 steps/day and 66 and 46 min/day of moderate to vigorous physical
      activity, respectively. The walking of 9,700 steps/day for boys and 9,400
      steps/day for girls ensures the scope of the recommendation of moderate to
      vigorous physical activity. CONCLUSIONS: In boys, steps/day and moderate to
      vigorous physical activity have been negatively associated with body mass index,
      regardless of race, family income, education of parents, screen time, diet
      pattern, and sedentary time. We suggest, for steps/day and moderate to vigorous
      physical activity, studies with different ages and populations, with different
      designs, so as to inform the cause and effect relationship with various health
      parameters. OBJETIVO: Estabelecer pontos de corte para o numero de passos/dia e
      min/dia de atividade fisica com intensidade moderada a vigorosa em relacao ao
      risco do excesso de peso e obesidade infantil e suas respectivas associacoes.
      Alem de identificar a quantidade de passos/dia necessarios para atingir a
      recomendacao de atividade fisica de moderada a vigorosa em criancas de Sao
      Caetano do Sul. METODOS: No total, 494 criancas usaram acelerometro para
      monitorar os passos/dia e a intensidade da atividade fisica (min/dia). A
      atividade fisica de moderada a vigorosa foi categorizada de acordo com a
      recomendacao de saude publica (<= 60 versus > 60 min/dia). Excesso de peso ou
      obesidade foi definido como indice de massa corporal > +1 DP, com base nos dados
      de referencia da Organizacao Mundial de Saude. Renda familiar, escolaridade dos
      pais, tempo de tela, padrao de dieta, e tempo sedentario foram coletados por
      questionarios. Foram construidas curvas Receiver Operating Characteristic e
      regressao logistica. RESULTADOS: Em media, os meninos realizaram mais passos/dia
      (1.850) e min/dia de atividade fisica de moderada a vigorosa (23,1) do que as
      meninas. No geral, 51,4% das criancas foram classificadas como eutroficas e 48,6%
      com excesso de peso ou obesidade. Meninos eutroficos realizavam 1.525 passos/dia
      e 18,6 min/dia de atividade fisica de moderada a vigorosa a mais do que aqueles
      com excesso de peso/obesidade (p < 0,05). O mesmo nao foi encontrado nas meninas
      (p > 0,05). Os pontos de corte para evitar excesso de peso e obesidade nos
      meninos e meninas foram 10.500 e 8.500 passos/dia e 66 e 46 min/dia de atividade
      fisica de moderada a vigorosa, respectivamente. A realizacao de 9.700 passos/dia
      (meninos) e 9.400 passos/dia (meninas) garante o alcance da recomendacao de
      atividade fisica de moderada a vigorosa. CONCLUSOES: Nos meninos, passos/dia e
      atividade fisica de moderada a vigorosa foram negativamente associados com o
      indice de massa corporal, independentemente da raca, renda familiar, escolaridade
      dos pais, tempo de tela, padrao de dieta e tempo sedentario. Sugere-se para
      passos/dia e atividade fisica de moderada a vigorosa, estudos em diversas idades
      e populacoes, com diferentes delineamentos, para assim informar a relacao causa e
      efeito com diversos parametros de saude.

PMID- 28489187
TI  - Teamwork: relevance and interdependence of interprofessional education.
AB  - OBJECTIVE: Determine the perception of university students regarding
      interprofessional and interdependent work between team members in their inclusion
      in primary care. METHODS: Analytical cross-sectional study. The sampling had a
      probabilistic, stratified random type with 95% confidence and 5% margin of error.
      Seven-hundred and four students of Public Universities in Santiago (Chile)
      answered self-administered questionnaire. RESULTS: Ninety-seven point eight of
      students say that interprofessional work is important; 27.1% of them declare that
      their university did not seem to show that their study plans were important. The
      professionals listed as most important in teams are physicians and nurses.
      CONCLUSIONS: Spaces for development and institutional support are key elements to
      promote interprofessional work. If this competence can involve each academic unit
      in their different formative spaces there will be a significant contribution to
      said promotion. Teamwork is a pending task. OBJETIVO: Determinar la percepcion de
      estudiantes universitarios respecto al trabajo interprofesional e
      interdependencia entre los miembros del equipo en su insercion en la atencion
      primaria. METODOS: Estudio de tipo analitico y transversal. El muestreo fue de
      tipo aleatorio, probabilistico estratificado con un 95% de confianza y un 5% de
      margen de error. Se utilizo un cuestionario auto-administrado en 704 estudiantes
      de Universidades del Estado en Santiago de Chile. RESULTADOS: Un 97,8% de los
      estudiantes opinan que el trabajo interprofesional es importante; un 27,1% de
      ellos declara que su universidad no le ha entregado importancia en sus planes de
      estudios. Los profesionales mencionados como mas importantes en el equipo son los
      medicos y enfermeras. CONCLUSIONES: Espacios de desarrollo y respaldo
      institucional son elementos claves para promover el trabajo interprofesional. Que
      esta competencia logre involucrar a cada unidad academica en sus diferentes
      espacios formativos sera un aporte significativo en aquello. Trabajo en equipo es
      una tarea pendiente.

PMID- 28489188
TI  - Cytogenotoxicity of rice crop water after application of the tricyclazole
      fungicide.
AB  - Tricyclazole is currently one of the fungicides recommended for the treatment of
      diseases in irrigated rice. However, there is relatively little information on
      its cytotoxic and genotoxic potential. The objective of this study was to
      evaluate the cytotoxicity and genotoxicity of rice crop water after apllication
      of the tricyclazole fungicide through the Allium cepa L. test. The rice crop
      water samplings were collected before and 1, 15 and 30 days after application of
      the fungicide in rice plant shoots. The Allium cepa roots were placed in contact
      with the rice crop water to check for possible chromosomal abnormalities and
      mitotic index of the bioindicators meristematic cells. The data obtained by the
      Allium cepa test indicates that the application of the tricyclazole fungicide
      leads to an increase in the genotoxic activity in the rice crop water, through
      the appearance of chromosomal abnormalities, without, however, causing
      significant effects on the mitotic index. The major chromosomal alterations
      observed were anaphasic and telophasic bridges and laggard chromosomes.

PMID- 28489189
TI  - Vitamin E and organic selenium for broilers from 22 to 42 days old: performance
      and carcass traits.
AB  - This study was conducted to evaluate the effect of vitamin E and selenium on
      performance, viability, productive efficiency, and yields of carcass, major cuts,
      and organs of broilers from 22 to 42 days submitted to cyclic-heat stress. The
      experimental design was randomized blocks, in a 2 * 3 factorial arrangement with
      two levels of selenium (0.1 and 0.3 mg/kg) and three levels of vitamin E (300,
      400, and 500 mg/kg), plus a control treatment. Animals were submitted to a
      natural condition of high cyclic temperature. Organic selenium levels of 0.1 and
      0.3 mg/kg associated with 300, 400, and 500 mg/kg of vitamin E were tested. The
      level of vitamin E did not affect the performance or production efficiency of
      broilers in the period from 22 to 33 days and 22 to 42 days. However, the
      selenium inclusion level of 0.3 mg/kg improved the viability in both phases. The
      yields of carcass, major cuts, intestine, and heart were not influenced by the
      levels of selenium and vitamin E, whereas abdominal fat for the selenium level
      0.1 mg/kg decreased linearly with the inclusion in vitamin E.

PMID- 28489190
TI  - Growth, photosynthetic pigments and production of essential oil of long-pepper
      under different light conditions.
AB  - Piper hispidinervum C. DC. is popularly known as long-pepper and it owns a
      commercial value due to the essential oil it produces. Long-pepper oil is rich in
      safrole and eugenoln components that have insecticidal, fungicidal and
      bactericidal activity. It has been establish that to medicinal plants light
      influences not only growth but also essential oil production. The growth, the
      content of photosynthetic pigments and the essential oil production of Piper
      hispidinervum at greenhouses with different light conditions was evaluated. The
      treatments were characterized by cultivation of plants for 180 days under
      different light conditions, produced by shading greenhouses with 50% and 30% of
      natural incident irradiance, two colored shading nets red (RN) and blue (BN) both
      blocking 50% of the incident radiation and one treatment at full-sun (0% of
      shade). The results showed that the treatments of 50% shade and RN and BN were
      the ones which stimulated the greater growth. Blue and red light also had the
      best production of photosynthetic pigments. Essential oil yielded more under full
      sun therefore this is the most indicated condition to produce seedlings for the
      chemical and pharmaceutical industry.

PMID- 28489191
TI  - Pathogenic Vibrio species isolated from estuarine environments (Ceara, Brazil) -
      antimicrobial resistance and virulence potential profiles.
AB  - Detection of virulent strains associated with aquatic environment is a current
      concern for the management and control of human and animal health. Thus, Vibrio
      diversity was investigated in four estuaries from state of Ceara (Pacoti, Choro,
      Pirangi and Jaguaribe) followed by antimicrobial susceptibility to different
      antimicrobials used in aquaculture and detection of main virulence factors to
      human health. Isolation and identification were performed on TCBS agar (selective
      medium) and dichotomous key based on biochemical characteristics, respectively.
      Nineteen strains of genus Vibrio were catalogued. Vibrio parahaemolyticus (Choro
      River) and V. alginolyticus (Pacoti River) were the most abundant species in the
      four estuaries. All strains were submitted to disk diffusion technique (15
      antimicrobials were tested). Resistance was found to: penicillin (82%),
      ampicillin (54%), cephalotin (7%), aztreonan (1%), gentamicin, cefotaxime and
      ceftriaxone (0.5%). Five pathogenic strains were chosen to verification of
      virulence factors. Four estuaries showed a high abundance of species. High number
      of tested positive strains for virulence is concerning, since some of those
      strains are associated to human diseases, while others are known pathogens of
      aquatic organisms.

PMID- 28489192
TI  - A new approach to feed frequency studies and protein intake regulation in
      juvenile pirarucu.
AB  - This study aimed to investigate pirarucu's (Arapaima gigas) ability to trigger a
      self-feeding system to regulate protein intake between two standard diets that
      contained 39% and 49% of crude protein. The same system allowed the evaluation of
      daily feeding and locomotor activity rhythms. Eighteen fish (654.44+/-26.85g)
      were distributed into six 250 L tanks (3 fish/tank). Fish had free access to both
      diets (39% vs. 49% protein) by feeders (2 per tank), adapted to be activated by
      fish themselves. This system was connected to a computer system. After an
      adaptation period, fish learned to activate feeders and the mean food intake
      recorded was 2.14% of their body weight on a daily basis. Fish showed feeding
      (72.48%) and locomotor (72.49%) activity predominantly during the daytime, and
      daily variations of choice between diets, but fixed a protein intake feeding
      target at 44.53%. These results should be considered when discussing feeding
      behavior, feeding schedules and diet intake regulations.

PMID- 28489193
TI  - Soluble amino acid profile, mineral nutrient and carbohydrate content of maize
      kernels harvested from plants submitted to ascorbic acid seed priming.
AB  - Both the scientific community and society have shown interest in improving the
      content of amino acids, carbohydrates and mineral nutrients in maize because it
      represents an important staple food in many developing countries. Earlier studies
      demonstrated that the treatment of seeds using ascorbic acid (AsA-seed priming)
      enhanced soluble carbohydrates, proteins and soluble amino acids for other
      species. AsA seed priming in maize showed the potential for reducing abiotic
      stresses. The effects on grain quality have not been previously demonstrated.
      This study investigated the impacts of AsA seed priming on maize kernel quality
      of seeds produced by the plants generated from the primed seeds, based on the
      amino acid profile and carbohydrate and mineral nutrient contents. AsA seed
      priming improved the maize kernel quality with respect to the ascorbate content,
      boron allocation, total carbohydrate content and increased soluble amino acid
      levels, including serine, tyrosine, alanine, valine, glutamate, arginine,
      proline, aspartate, lysine and isoleucine, whereas soluble methionine was
      decreased. Therefore, AsA seed priming can represent a potential technique for
      improving maize grain quality.

PMID- 28489194
TI  - Antiproliferative activity in tumor cell lines, antioxidant capacity and total
      phenolic, flavonoid and tannin contents of Myrciaria floribunda.
AB  - Myrciaria floribunda (H. West ex Willd.) O. Berg, Myrtaceae, is a native plant
      species of the Atlantic Rain Forest, from north to south of Brazil. The
      lyophilized ethyl acetate extract from the leaves of M. floribunda was
      investigated for its antiproliferative activity in tumor cell lines, antioxidant
      capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative
      activity was tested in vitro against seven human cancer cells and against
      immortalized human skin keratinocytes line (HaCat, no cancer cell). Antioxidant
      activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging and oxygen radical absorbing capacity (ORAC) assays and total
      phenolic, flavonoid and tannin contents were determined by spectrophotometric
      techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative
      activity against cancer cell lines with total growth inhibition (TGI) between
      69.70 and 172.10 ug/mL. For HaCat cell, TGI value was 213.60 ug/mL. M. floribunda
      showed a strong antioxidant potential: EC50 of 45.89+/-0.42 ug/mL and 0.55+/-0.05
      mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23+/
      0.013g gallic acid equivalents (GAE)/g extract and exhibited 13.10+/-1.60% of
      tannins content. The content of flavonoid was 24.08+/-0.44% expressed as rutin
      equivalents. These results provide a direction for further researches about the
      antitumoral potential of M. floribunda.

PMID- 28489195
TI  - BEEF TALLOW AND EMULSIFIER IN GROWING-FINISHING PIG DIETS.
AB  - Two trials were aimed to evaluate beef tallow in diets with and without
      emulsifier on performance of pigs at growing-finishing phases. In the first
      trial, 15 barrows (22.03+/-0.62 kg) were distributed among three treatments:
      reference diet; test diet 1 (5% beef tallow) and test diet 2 (10% beef tallow).
      Beef tallow presented average value of 7130.97 kcal ME/kg. For the performance
      trail, 30 barrows (24.85+/-1.18 kg) were distributed among five treatments: T1 -
      diet with soybean oil and 3230 kcal ME /kg; T2 - diet with beef tallow and 3230
      kcal ME/kg; T3 - diet with beef tallow and 3080 kcal ME/kg; T4 - diet with beef
      tallow, 3080 kcal/kg and 0.1% emulsifier; T5 - diet with beef tallow, 2930 kcal
      ME/kg and 0.1% emulsifier. Feed conversion was worse in animals fed diet with
      3080 kcal ME/kg containing beef tallow and with 2930 kcal ME/kg with beef tallow
      and emulsifier. For economic availability, animals fed diet with beef tallow and
      3230 kcal ME/kg and those fed diet with 3080 kcal ME/kg containing beef tallow
      and emulsifier, did not differ from animals fed diet with soybean oil, which
      enables the reduction up to 150 kcal ME/kg be compensated by emulsifier addition.

PMID- 28489196
TI  - Parasite infracommunities of Leporinus friderici : A comparison of three
      tributaries of the Jurumirim Reservoir in southeastern Brazil.
AB  - The degradation and homogenization of natural habitats is considered a major
      cause of biotic homogenization. Many studies have been undertaken on the effects
      of dams on aquatic wildlife, in particular fish assemblages. But how do dams
      affect the parasitic fauna of such fish? The aim of the present study was to
      examine parasitic similarity, comparing the diversity and structure of parasite
      communities of Leporinus friderici (Characiformes, Anostomidae) in three upstream
      tributaries under the influence of the Jurumirim Dam on the Upper Paranapanema
      River in southeastern Brazil. The present study did not find any significant
      differences in parasite communities among populations of L. friderici in the
      three upstream tributaries. This result highlights that dams promote and
      facilitate the dispersal of organisms between localities, and therefore the
      spatial homogenization of parasite communities. Overall, the results suggest that
      fish parasite assemblages can provide suitable data for evaluating biotic
      homogenization caused by dams.

PMID- 28489197
TI  - Population dynamics of Rimapenaeus constrictus (Stimpson, 1874) (Penaeoidea) on
      the southeastern Brazilian coast: implications for shrimp fishing management from
      a 5-year study on a bycatch species.
AB  - This is the first study to evaluate in broad spatiotemporal scales the growth
      parameters and population structure of Rimapenaeus constrictus, a barely damaged
      species composing the bycatch from shrimp fishing in the Western Atlantic. The
      abundance and size-class frequency distribution, growth, longevity and sex ratio
      were evaluated from monthly samples obtained in the northern littoral of Sao
      Paulo state from Jan/1998 to Jun/2003. We measured 5,812 individuals in which the
      sex ratio was skewed toward females; this was more evident in size classes
      greater than 10 mm in CL (carapace length) (binomial test, p<0.05). We selected
      16 growth cohorts of females, and 8 of males, the majority consisting of younger
      individual cohorts excluded from the fisheries closure period. Growth estimates
      resulted in a CLinfinity of 17.42 mm, a growth coefficient of 0.008 and a
      longevity of 579 days (1.60 year) for females, as well as a CLinfinity of 16.3
      mm, a growth coefficient of 0.01 and a longevity of 425 days (1.17 year) for
      males. Our results provide information of incontestable relevance to our
      knowledge of fishing management. We therefore strongly recommend that the
      fisheries closure period be changed to protect this species' recruitment period
      and consequently its adult individuals.

PMID- 28489198
TI  - Are the dinosauromorph femora from the Upper Triassic of Hayden Quarry (New
      Mexico) three stages in a growth series of a single taxon?
AB  - The lagerpetid Dromomeron romeri and the theropod Tawa hallae are two
      dinosauromorphs from the Norian (Upper Triassic) of the Chinle Formation,
      situated in New Mexico, USA. However, a recent study suggests the inclusion of
      the holotype of D. romeri (GR 218) and paratype (GR 155) and referred (GR 235)
      specimens of T. hallae in an ontogenetic series of a single species. The
      specimens GR 218 and GR 155 include just an isolated femur, while GR235 includes
      femora, pelvis and tail. The inclusion of the specimens in an unique ontogenetic
      series relies on the putative immature condition and plastic deformation of the
      specimen GR 218. However, as observed here, the disparity between the femora of
      D. romeri and T. hallae is considerably higher than those expected from the
      ontogenetic variance in dinosauromorphs. In addition, D. romeri shares an unique
      suite of traits with Dromomeron gigas, a species known from a mature specimen.
      Therefore, the high disparity between D. romeri and T. hallae, lack of traits
      shared solely between the three femora, and a suite of traits shared between D.
      romeri and D. gigas, precludes the inclusion of the three femora from Hayden
      Quarry in a growth series of a single taxon.

PMID- 28489199
TI  - Compatibility of Azospirillum brasilense and Pseudomonas fluorescens in growth
      promotion of groundnut ( Arachis hypogea L.).
AB  - We attempted to study the compatibility among plant beneficial bacteria in the
      culture level by growing them near in the nutrient agar plates. Among all the
      bacteria tested, Rhizobium was found to inhibit the growth of other bacteria.
      From the compatible group of PGPR, we have selected one biofertilizer
      (Azospirillum brasilense strain TNAU) and one biocontrol agent (Pseudomonas
      fluorescens strain PF1) for further studies in the pot culture. We have also
      developed a bioformulation which is talc powder based, for individual bacteria
      and mixed culture. This formulation was used as seed treatment, soil application,
      seedling root dip and foliar spray in groundnut crop in vitro germination
      conditions. A. brasilense was found to enhance the tap root growth and P.
      fluorescens, the lateral root growth. The other growth parameters like shoot
      growth, number of leaves were enhanced by the combination of both of the bacteria
      than their individual formulations. Among the method of application tested in our
      study, soil application was found to be the best in yielding better results of
      plant growth promotion.

PMID- 28489200
TI  - A new species of Tereancistrum (Monogenea, Dactylogyridae) from the gills of
      three Leporinus species (Characiformes, Anostomidae) and a revised description of
      Tereancistrum parvus.
AB  - The present study describes Tereancistrum flabellum n. sp. (Dactylogyridae,
      Ancyrocephalinae) from the gills of the anostomid fishes Leporinus friderici,
      Leporinus amblyrhynchus and Leporinus elongatus from two freshwater ecosystems in
      the south east of Brazil. This new species is mainly characterized by the
      morphology of the copulatory complex (such as the MCO base formed by two fan
      shaped structures, and accessory piece flattened, curved, rigid and channeled), a
      dorsal anchor with a well-developed superficial and inconspicuous deep root, and
      the shape of the accessory anchor sclerite with small spathulate termination.
      Tereancistrum flabellum n. sp. is the first record of a dactylogyrid from L.
      amblyrhynchus. The description of Tereancistrum parvus is also emended to correct
      and complement previous descriptions and the species is reported for the first
      time in Schizodon nasutus.

PMID- 28489201
TI  - Water temperature, body mass and fasting heat production of pacu (Piaractus
      mesopotamicus).
AB  - Knowledge on fasting heat production (HEf) of fish is key to develop
      bioenergetics models thus improving feeding management of farmed species. The
      core of knowledge on HEf of farmed, neotropical fish is scarce. This study
      assessed the effect of body mass and water temperature on standard metabolism and
      fasting heat production of pacu, Piaractus mesopotamicus, an omnivore,
      Neotropical fresh water characin important for farming and fisheries industries
      all through South American continent. An automated, intermittent flow
      respirometry system was used to measure standard metabolic rate (SMR) of pacu (17
      - 1,050 g) at five water temperatures: 19, 23, 26, 29 and 33  degrees C. Mass
      specific SMR increased with increasing water temperature but decreased as
      function of body mass. The allometric exponent for scaling HEf was 0.788, and
      lied in the range recorded for all studied warm-water fish. The recorded van't
      Hoff factor (Q10) for pacu (2.06) shows the species low response to temperature
      increases. The model HEf = 0.04643*W0.7882*T1.837 allows to predict HEf (kJ d-1)
      from body mass (W, kg) and water temperature (T,  degrees C), and can be used in
      bioenergetical models for the species.

PMID- 28489202
TI  - Diversity and distribution of epiphytic bromeliads in a Brazilian subtropical
      mangrove.
AB  - It is not unusual to find epiphytic bromeliads in mangroves, but most studies on
      mangrove vegetation do not record their presence. This study aimed to evaluate
      the diversity and distribution of epiphytic bromeliads in a subtropical mangrove.
      The richness, abundance and life form (atmospheric and tank) of bromeliads were
      recorded and compared among host tree species and waterline proximity. The
      effects of diameter and height of host trees on the abundance of bromeliads were
      also assessed. The mangrove was composed of Avicennia schaueriana, Laguncularia
      racemosa and Rhizophora mangle. We recorded seven bromeliad species of the genera
      Tillandsia and Vriesea. The waterline proximity did not affect the abundance or
      diversity of bromeliads, but atmospheric forms were predominant near the
      waterline, whereas tank bromeliads were more frequent in the interior of the
      mangrove. The three mangrove species hosted bromeliads, but L. racemosa was the
      preferred host. The species composition showed that the distribution of
      bromeliads is more related to the host species than to the distance from the
      waterline. Bromeliad abundance increased with tree size. Bromeliads can be
      biological indicators of ecosystem health; therefore, inventories and host tree
      preferences are necessary knowledge for an adequate management of sensitive
      ecosystems as mangroves.

PMID- 28489203
TI  - Evaluation of methods for the quantification of ether extract contents in forage
      and cattle feces.
AB  - The objective of this study was to compare the estimates of ether extract (EE)
      contents obtained by the Randall method and by the high-temperature method of the
      American Oil Chemist's Society (AOCS; Am 5-04) in forages (n = 20) and cattle
      feces (n = 15). The EE contents were quantified by using the Randall extraction
      or AOCS method and XT4 filter bags or cartridges made of qualitative filter paper
      (80 g/m2) as containers for the samples. It was also evaluated the loss of
      particles, and concentration of residual chlorophyll after extraction and the
      recovery of protein and minerals in the material subjected to extraction.
      Significant interaction was observed between extraction method and material for
      EE contents. The EE estimates using the AOCS method were higher, mainly in
      forages. No loss of particles was observed with different containers. The
      chlorophyll contents in the residues of cattle feces were not affected by the
      extraction method; however, residual chlorophyll was lower using the AOCS method
      in forages. There was complete recovery of the protein and ash after extraction.
      The results suggest that AOCS method produces higher estimates of EE contents in
      forages and cattle feces, possibly by providing greater extraction of non-fatty
      EE.

PMID- 28489204
TI  - Have the current and promising therapeutic options changed the surgeon's role in
      the treatment of pancreatic cancer?

PMID- 28489205
TI  - Profile of the appendectomies performed in the Brazilian Public Health System.
AB  - Objective: to analyze the profile of appendectomies performed in the Brazilian
      Public Health System (SUS) and to compare the laparoscopic and laparotomic
      techniques of appendectomy. Methods: This work used information from DataSus from
      2008 to 2014 (http://datasus.saude.gov.br). We compared the data of patients
      submitted to laparotomic appendectomy with those submitted to laparoscopic one.
      Results: when comparing the total growth of appendectomies, the laparoscopic
      route increased 279.7%, while the increase in laparotomic surgery was 25% (p
      <0.001) in the study period. With regard to medical and hospital costs,
      laparoscopic appendectomy accounted for only 2.6% of the total expenditure on
      appendectomies performed by the Unified Health System (SUS) hospitals, with an
      average cost 7.6% lower than that of laparotomy procedures, but without
      statistical significance. The mortality rate was 57.1% lower in the laparoscopic
      approach when compared with laparotomy. Conclusion: there has been a significant
      increase in the laparoscopic route in the treatment of appendicitis, but the
      method is still rarely used in SUS patients. The costs of laparoscopic
      appendectomy were similar to those observed in laparotomic access.

PMID- 28489206
TI  - Lower extremity reconstruction: epidemiology, management and outcomes of patients
      of the Federal District North Wing Regional Hospital.
AB  - Objective: to evaluate the management of lower limbs complex traumatic injuries
      by analyzing their characteristics, types, conduct and evolution, with emphasis
      on surgical treatment. Methods: we conducted a prospective study of patients
      treated by Plastic Surgery at a regional hospital of the Federal District during
      a one-year period. We collected data through serial evaluations and telephone
      contact records. Results: we studied 40 patients, with a mean age of 25.6 years,
      predominantly male (62.5%). The most frequent wounds were of the distal third of
      the lower limb (37.5%). Bone or tendon exposures occurred in 55% had and there
      was a 35% rate of exposed lower limb fractures. The treatments employed were skin
      grafting (57.5%), local fasciocutaneous flap (15%), muscle flap (12.5%), cross
      leg fasciocutaneous flap, reverse sural flap (12.5%) and microsurgical flap
      (2.5%). Short-term evaluation showed that 35 patients had excellent or good
      results (87.5%), four had a regular result (10%), and one had an unsatisfactory
      result (2.5%). In the long term, of the 18 patients who answered the
      questionnaire, ten resumed walking, even with support, in the first three months
      after surgery (55.6%). Conclusion: young men involved in motorcycle accidents
      during leisure time represented the profile of patients with lower limb trauma
      requiring surgical reconstruction; the distal third of the leg was the most
      affected region. Grafting was the most used technique for reconstruction and
      postoperative functional evaluation showed that, despite complex lesions, most
      patients evolved with a favorable healing process and successful functional
      evolution.

PMID- 28489207
TI  - Conversion of Plastic Surgery meeting abstract presentations to full manuscripts:
      a brazilian perspective.
AB  - Objective: to assess the conversion rate of Plastic Surgery meeting abstract
      presentations to full manuscript publications and examine factors associated with
      this conversion. Methods: we assessed the abstracts presented at the 47th and
      48th Brazilian Congresses of Plastic Surgery by cross-referencing with multiple
      databases. We analyzed the Abstracts' characteristics associated with full
      manuscript publications. Results: of the 200 abstracts presented, 50 abstracts
      were subsequently published in full, giving the conference a conversion rate of
      25%. The mean time to publish was 15.00+/-13.75 months. In total, there were
      4.93+/-1.63 authors per abstract and 67.8+/-163 subjects per abstract; 43.5% of
      the abstracts were of retrospective studies; 69% comprised the plastic surgery
      topics head and neck, and chest and trunk, and 88.5% had no statistical analysis.
      Overall, 80% of the manuscripts were published in plastic surgery journals, 76%
      had no impact factor and 52% had no citations. Bivariate and multivariate
      analyses revealed the presence of statistical analysis to be the most significant
      (p<0.05) predictive factor of conversion of abstracts into full manuscripts.
      Conclusion: the conversion rate found from this bibliometric research appeared a
      bit lower than the conversion trend of international plastic surgery meetings,
      and statistical analysis was a determinant of conversion success.

PMID- 28489208
TI  - Profile of thoracic trauma victims submitted to chest drainage.
AB  - Objective: to describe and compare the variables involved in trauma victims
      undergoing thoracic drainage. Methods: we conducted a retrospective, analytical,
      descriptive, cross-sectional study, with medical records of patients attended at
      the Trauma Service of the Curitiba Evangelical University Hospital between
      February 2011 and January 2014. Results: there were 488 patients undergoing chest
      drainage, 84.7% men and 15.3% women, with an average age of 38.2 years.
      Attendances usually occurred at night, without predominance between open or
      closed mechanism, gender or age group. The majority of patients with thoracic
      trauma requiring drainage were diagnosed by anamnesis and physical examination
      (41.1%) and drained in the emergency room (80.8%). Most of the patients (66.2%)
      had another associated lesion, mostly some abdominal viscera. Complications were
      present in 16.6% (81 patients), most of them due to drainage positioning error
      (9.2%). The mean hospital stay was 15 days and drainage lasted for an average of
      8.1 days, with no statistical difference between open and closed trauma. The
      clinical outcome was discharge in most cases. Conclusion: the profile of patients
      with thoracic trauma is that of young men, attended at night, with some other
      associated lesion. Although diagnosis and treatment were rapid and most often
      without the need for complex examinations, the time of drainage, hospitalization
      and complications were higher than in the literature, which can be explained by
      the drainage being made at the Emergency Room and the presence of associated
      injuries.

PMID- 28489209
TI  - Bone grafting for alveolar ridge reconstruction. Review of 166 cases.
AB  - Objective: : to investigate the predictive factors of failure in bone grafts for
      alveolar ridge augmentation and implant surgery. Methods: : we reviewed the
      charts of 166 patients operated between 1995 and 2014. A total of 248 grafting
      procedures were performed. We submitted the data to the binomial test at 5%
      significance. Results: : grafts to gain width of the alveolar ridge (65.32%) were
      more frequent than sinus lifting (p<0.0001) and the number of grafts to the
      posterior maxilla (48.8%) was greater than in other regions (p<0.01); 6.04% of
      the grafts were lost. The losses in anterior (p<0.0309) and posterior (p<0.0132)
      maxilla were higher than in the mandible. There were 269 implants installed in
      the grafted areas, of which only 4.83% were lost. The number of implants lost
      (4.51%) in areas of onlay grafts was not statistically higher than those placed
      after sinus lifting (2.63%, p<0.2424). Losses were greater in the anterior
      (53.85%) and posterior (38.46%) maxilla than in the mandible (p<0.031). Regarding
      patients' age, 76.92% of the lost grafts (p<0.006) and 80% of the lost implants
      (p<0.001) were installed in patients over 40 years. Conclusion: : failure rate
      was higher both for grafts and dental implants in the maxilla and in patients
      over 40 years of age. Objetivo: : investigar os fatores preditivos de falhas em
      enxertos osseos para aumento do rebordo alveolar e cirurgia de implantes.
      Metodos: : os prontuarios de 166 pacientes, operados entre 1995 e 2014, foram
      revistos. Um total de 248 enxertos foi realizado. Os dados foram submetidos ao
      teste binomial a 5% de significancia. Resultados: : os enxertos para ganho em
      espessura do rebordo alveolar (65,32%) foram mais frequentes do que levantamentos
      de seio maxilar (p<0,0001) e o numero de enxertos para a regiao posterior da
      maxila (48,8%) foi maior do que em outras regioes (p<0,01). Foram perdidos 6,04%
      dos enxertos. As perdas em maxila anterior (p<0,0132) e posterior (p<0,0309)
      foram maiores do que na mandibula. Foram instalados 269 implantes nas areas
      enxertadas e apenas 4,83% perdidos. O numero de implantes perdidos (4,51%) em
      areas de enxertos em bloco nao foi estatisticamente maior do que na area de seios
      maxilares enxertados (2,63%) (p<0,2424). As perdas foram maiores na regiao
      anterior (53,85%) e posterior (38,46%) da maxila em relacao a mandibula (p<0,031)
      e, 76,92% dos enxertos (p<0,006) e 80% dos implantes perdidos (p<0,001), foram
      instalados em pacientes com mais de 40 anos de idade. Conclusao: : maior taxa de
      falhas foi observada para enxertos e implantes dentarios realizados em maxila e
      em pacientes com mais de 40 anos de idade.

PMID- 28489210
TI  - Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese
      patients.
AB  - Objective: to determine the ED90 (minimum effective dose in 90% of patients) of
      sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade
      (NMB) in patients with grade III obesity undergoing bariatric surgery. Methods:
      we conducted a prospective study with the biased coin up-and-down sequential
      design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg,
      2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1
      ratio >=0.9 as measured by TOF. After induction of general anesthesia and
      calibration of the peripheral nerve stimulator and accelerometer, we injected
      rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous
      infusion, and intermittent boluses of rocuronium throughout the procedure.
      Results: we evaluated 31 patients, of whom 26 had displayed successful reversal
      of the NMB with sugammadex, and failure in five. The mean time to complete
      moderate NMB reversal was 213 seconds (172-300, median 25-75%). The ED90 of
      sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval
      of 2.27-2.46 mg/kg. Conclusion: the ED90 of sugammadex in patients with grade III
      obesity or higher was 2.39mg/kg.

PMID- 28489211
TI  - Endovascular treatment of carotid-cavernous vascular lesions.
AB  - Objective: : to evaluate the endovascular treatment of vascular lesions of the
      cavernous segment of the internal carotidartery (ICA) performed at our
      institution. Methods: : we conducted a descriptive, retrospective and prospective
      study of patients with aneurysms of the cavernous portion of the ICA or with
      direct carotid-cavernous fistulas (dCCF) undergoing endovascular treatment.
      Results: : we included 26 patients with intracavernous aneurysms and ten with
      dCCF. All aneurysms were treated with ICA occlusion. Those with dCCF were treated
      with occlusion in seven cases and with selective fistula occlusion in the
      remaining three. There was improvement of pain and ocular proptosis in all
      patients with dCCF. In patients with intracavernous aneurysms, the incidence of
      retro-orbital pain fell from 84.6% to 30.8% after treatment. The endovascular
      treatment decreased the dysfunction of affected cranial nerves in both groups,
      especially the oculomotor one. Conclusion: : the endovascular treatment
      significantly improved the symptoms in the patients studied, especially those
      related to pain and oculomotor nerve dysfunction. Objetivo: : avaliar o
      tratamento endovascular de lesoes vasculares da arteria carotida interna (ACI),
      segmento cavernoso, realizado na Santa Casa de Sao Paulo. Metodos: : estudo
      descritivo, retrospectivo e prospectivo, de pacientes com aneurisma da porcao
      cavernosa da ACI ou com fistulas carotido-cavernosas diretas (FCCd) submetidos a
      tratamento endovascular. Resultados: : foram incluidos 26 pacientes com
      aneurismas intracavernosos e dez com FCCd. Todos os aneurismas foram tratados com
      oclusao da ACI. Os com FCCd foram tratados com oclusao, em sete casos, e com
      oclusao seletiva da fistula nos outros tres. Houve melhora da dor e proptose
      ocular em todos os pacientes com FCCd. Nos pacientes com aneurisma
      intracavernoso, a incidencia de dor retro-orbitaria caiu de 84,6% para 30,8% apos
      o tratamento. Apos o tratamento endovascular houve uma melhora importante da
      disfuncao de nervos cranianos afetados em ambos os grupos, sobretudo no nervo
      oculomotor. Conclusao: : o tratamento endovascular trouxe melhora para os
      pacientes deste estudo, especialmente nos criterios dor e acometimento do nervo
      oculomotor.

PMID- 28489212
TI  - Impact of using a local protocol in preoperative testing: blind randomized
      clinical trial.
AB  - Objective: to evaluate the impact of the use of a local protocol of preoperative
      test requests in reducing the number of exams requested and in the occurrence of
      changes in surgical anesthetic management and perioperative complications.
      Methods: we conducted a randomized, blinded clinical trial at the Gaffree and
      Guinle University Hospital with 405 patients candidates for elective surgery
      randomly divided into two groups, according to the practice of requesting
      preoperative exams: a group with non-selectively requested exams and a protocol
      group with exams requested according to the study protocol. Studied exams:
      complete blood count, coagulogram, glycemia, electrolytes, urea and creatinine,
      ECG and chest X-ray. Primary outcomes: changes in surgical anesthetic management
      caused by abnormal exams, reduction of the number of exams requested after the
      use of the protocol and perioperative complications. Results: there was a
      significant difference (p<0.001) in the number of exams with altered results
      between the two groups (14.9% vs. 29.1%) and a reduction of 57.3% in the number
      of exams requested between the two groups (p<0.001), which was more pronounced in
      patients of lower age groups, ASA I, without associated diseases and submitted to
      smaller procedures. There was no significant difference in the frequency of
      conduct changes motivated by the results of exams or complications between the
      two groups. In the multivariate analysis, complete blood count and coagulogram
      were the only exams capable of modifying the anesthetic-surgical management.
      Conclusion: the proposed protocol was effective in eliminating a significant
      number of complementary exams without clinical indication, without an increase in
      perioperative morbidity and mortality.

PMID- 28489213
TI  - Effects of heparin and hyperbaric oxygenation on necrosis reduction in an animal
      model for degloving injuries.
AB  - Objective: : to evaluate the efficacy of the treatment with hyperbaric oxygen
      therapy or with topical and intralesional heparin in an animal model of degloving
      lesions. Methods: : we conducted an experimental study with adult, male Wistar
      rats submitted to degloving of the left hind limb and divided into four groups
      according to the treatment: Group 1 (control) - without treatment; Group 2
      (Heparin) - intralesional application at the time of surgery and topically, in
      the postoperative period, with heparin spray 10,000IU/mL; Group 3 (hyperbaric
      oxygenation) - daily sessions of 30 minutes in a hyperbaric chamber with 100%
      oxygen and 2 ATA pressure; Group 4 (positive control) - administration of a
      single dose of 45 mg/kg of intraperitoneal allopurinol. On the seventh day, we
      killed the animals, removed the cutaneous flaps and measured the total and
      necrotic areas, as well as computed the percentage of necrotic area. Results: :
      the mean percentage of necrosis in the control group was 56.03%; in the positive
      control group it was 51.36% (p<0.45); in the heparin group, 42.10% (p<0.07); and
      in the hyperbaric oxygen therapy group, 31.58% (p<0.01) . Conclusion: : both
      hyperbaric oxygen and heparin therapies were effective in reducing the percentage
      of necrosis in the model studied, although only the hyperbaric oxygenation showed
      statistical significance. Objetivos: : avaliar a eficacia do tratamento com
      oxigenoterapia hiperbarica ou com heparina topica e intralesional em modelo
      animal de desluvamentos. Metodos: : estudo experimental, com ratos adultos machos
      Wistar, submetidos a desluvamento do membro posterior esquerdo e divididos em
      quatro grupos, de acordo com o tratamento: Grupo 1 (controle) - sem tratamento;
      Grupo 2 (Heparina) - aplicacao intralesional no momento da cirurgia e topica, no
      pos operatorio, com spray de heparina 10.000UI/mL; Grupo 3 (oxigenacao
      hiperbarica) - sessoes diarias de 30 minutos em camara hiperbarica com 100% de
      oxigenio e 2 ATA de pressao; Grupo 4 (controle positivo) - administracao de dose
      unica de 45mg/kg de alopurionol intraperitoneal. No setimo dia os animais foram
      mortos e os retalhos cutaneos foram retirados e realizadas medidas das areas
      total e necrotica, bem como calculo da porcentagem da area de necrose.
      Resultados: : a media da porcentagem de necrose do grupo controle foi 56,03%; no
      grupo controle positivo, 51,36% (p<=0,45); no grupo da heparina, 42,10% (p<=0,07)
      e no grupo da oxigenoterapia hiperbarica, 31,58% (p<=0,01). Conclusao: : tanto a
      oxigenoterapia hiperbarica quanto a terapia com heparina mostraram-se eficazes na
      reducao do percentual de necrose no modelo estudado, embora neste trabalho apenas
      a oxigenacao hiperbarica tenha demonstrado significancia estatistica.

PMID- 28489215
TI  - Negative pressure therapy for the treatment of complex wounds.
AB  - The objective of this study is to evaluate the effectiveness of negative pressure
      therapy (NPT) in the treatment of complex wounds, with emphasis on its mechanisms
      of action and main therapeutic indications. We searched the Pubmed / Medline
      database for articles published from 1997 to 2016, and selected the most relevant
      ones. The mechanisms of action of NPT involveboth physical effects, such as
      increased perfusion, control of edema and exudate, reduction of wound dimensions
      and bacterial clearance, and biological ones, such as the stimulation of
      granulation tissue formation, microdeformations and reduction of Inflammatory
      response. The main indications of NPT are complex wounds, such as pressure
      ulcers, traumatic wounds, operative wound dehiscences, burns, necrotizing wounds,
      venous ulcers, diabetic wounds, skin grafts, open abdomen, prevention of
      complications in closed incisions and in the association with instillation of
      solutions in infected wounds.

PMID- 28489214
TI  - Efficacy of bacterial cellulose membrane for the treatment of lower limbs chronic
      varicose ulcers: a randomized and controlled trial.
AB  - Objective: to evaluate the efficacy of Bacterial Cellulose (BC) membrane
      dressings in the treatment of lower limb venous ulcers. Methods: we carried out a
      prospective, randomized, controlled study of 25 patients with chronic venous
      ulcer disease in the lower limbs from the Angiology and Vascular Surgery Service
      of the Federal University of Pernambuco Hospital and from the Salgado Polyclinic
      of the County Health Department, Caruaru, Pernambuco. We randomly assigned
      patients to two groups: control group, receiving dressings with triglyceride oil
      (11 patients) and experimental group, treated with BC membrane (14 patients). We
      followed the patients for a period of 120 days. Results: There was a reduction in
      the wound area in both groups. There were no infections or reactions to the
      product in any of the groups. Patients in the BC group showed decreased pain and
      earlier discontinuation of analgesic use. Conclusion: BC membrane can be used as
      a dressing for the treatment of varicose ulcers of the lower limbs.

PMID- 28489216
TI  - The role of surgery in the management of women with gestational trophoblastic
      disease.
AB  - The Gestational Trophoblastic Disease includes an interrelated group of diseases
      originating from placental tissue, with distinct behaviors concerning local
      invasion and metastasis. The high sensitivity of the serial dosages of human
      chorionic gonadotrophin, combined with advances in chemotherapy treatment, have
      made gestational trophoblastic neoplasia curable, most often through
      chemotherapy. However, surgery remains of major importance in the management of
      patients with gestational trophoblastic disease, improving their prognosis.
      Surgery is necessary in the control of the disease's complications, such as
      hemorrhage, and in cases of resistant/relapsed neoplasia. This review discusses
      the indications and the role of surgical interventions in the management of women
      with molar pregnancy and gestational trophoblastic neoplasia. RESUMO Doenca
      trofoblastica gestacional inclui um grupo interrelacionado de doencas originadas
      do tecido placentario, com tendencias distintas de invasao local e metastase. A
      alta sensibilidade das dosagens seriadas de gonadotrofina corionica humana aliada
      aos avancos do tratamento quimioterapico tornou a neoplasia trofoblastica
      gestacional, curavel, na maioria das vezes, atraves da quimioterapia. No entanto,
      a cirurgia permanece ainda, da maior importancia na conducao de pacientes com
      doenca trofoblastica gestacional, melhorando seu prognostico. A cirurgia e
      necessaria no controle de complicacoes da doenca, tais como hemorragia, e em
      casos de neoplasia resistente/recidivada. Esta revisao discute as indicacoes e o
      papel das intervencoes cirurgicas durante o manejo de mulheres com gravidez molar
      e neoplasia trofoblastica gestacional.

PMID- 28489217
TI  - Intra-aortic balloon pump in cardiogenic shock: state of the art.
AB  - The clinical definition of cardiogenic shock is that of a low cardiac output and
      evidence of tissue hypoxia in the presence of adequate blood volume. Cardiogenic
      shock is the main cause of death related to acute myocardial infarction (AMI),
      with a mortality rate of 45-70% in the absence of aggressive and highly
      specialized technical care. The intra-aortic balloon pump (IABP) is one of the
      most widely used mechanical assisting devices. During the last two decades, about
      42% of patients with AMI who evolved with cardiogenic shock received mechanical
      circulatory assistance with IABP. Its clinical indication has been based on non
      randomized studies and registry data. Recent studies have shown that the use of
      IABP did not reduce 30-day mortality in patients with AMI and cardiogenic shock
      treated with the strategy of early myocardial revascularization as the planned
      primary objective. The guidelines of the American Heart Association and of the
      European Society of Cardiology have reassessed their recommendations based on the
      results of meta-analyzes, including the IABP-SCHOCK II Trial study, which did not
      evidence an increase in survival of patients who received mechanical support with
      IABP. This review article addresses the clinical impact of IABP use in the
      cardiogenic shock caused by AMI. RESUMO A definicao clinica de choque
      cardiogenico e a de um quadro de baixo debito cardiaco e evidencia de hipoxia
      tecidual, na presenca de volemia adequada. O choque cardiogenico representa a
      principal causa de obito relacionada ao infarto agudo do miocardio (IAM), com
      indice de mortalidade em torno de 45% a 70%, na ausencia de cuidados tecnicos
      agressivos e altamente especializados. O balao intra-aortico (BIA) e um dos
      dispositivos de assistencia mecanica mais utilizados no mundo. Nas duas ultimas
      decadas, cerca de 42% dos pacientes com IAM, que evoluiram com choque
      cardiogenico, receberam assistencia circulatoria mecanica com BIA. Sua indicacao
      clinica tem sido baseada em estudos nao randomizados e dados de registro. Estudos
      recentes tem demonstrado que o uso do BIA nao reduziu a mortalidade hospitalar
      (30 dias) em pacientes com IAM e choque cardiogenico, tratados com a estrategia
      de revascularizacao precoce do miocardio como objetivo primario planejado. As
      diretrizes da Associacao Americana de Cardiologia e da Sociedade Europeia de
      Cardiologia reavaliaram suas recomendacoes, baseadas nos resultados de
      metanalises, incluindo o estudo IABP-SCHOCK II Trial, que nao evidenciou aumento
      na sobrevida de pacientes que receberam suporte mecanico com BIA. Este artigo de
      revisao aborda o impacto clinico do uso do BIA no choque cardiogenico ocasionado
      pelo IAM.

PMID- 28489218
TI  - Percutaneous transbiliary biopsy.
AB  - Percutaneous drainage of the bile ducts is an established procedure for malignant
      obstructions, in which a histological diagnosis is often not obtained. We
      describe the biopsy technique of obstructive lesions through biliary drainage
      access, using a 7F endoscopic biopsy forceps, widely available; some are even
      reusable. This technique applies to lesions of the hepatic ducts, of the common
      hepatic duct and of all extension of the common bile duct. RESUMO A drenagem
      percutanea das vias biliares e um procedimento estabelecido para obstrucoes
      malignas, nos quais, muitas vezes, nao se consegue um diagnostico histologico.
      Descrevemos a tecnica de biopsia da lesao obstrutiva atraves do acesso de
      drenagem biliar, utilizando um forcipe de biopsia endoscopica 7F, amplamente
      disponivel e alguns reutilizaveis. Esta tecnica aplica-se a lesoes dos ductos
      hepaticos, do hepatico comum e de toda extensao do coledoco.

PMID- 28489219
TI  - Appraisal of levels and patterns of occupational exposure to 1,3-butadiene.
AB  - Objectives 1,3-butadiene is classified as carcinogenic to human by inhalation and
      the association with leukemia has been observed in several epidemiological
      studies. The aim of this study was to evaluate data about occupational exposure
      levels to 1,3-butadiene in the Italian working force. Methods Airborne
      concentrations of 1,3-butadiene were extracted from the Italian database on
      occupational exposure to carcinogens in the period 1996-2015. Descriptive
      statistics were calculated for exposure-related variables. An analysis through
      linear mixed model was performed to determine factors influencing the exposure
      level. The probability of exceeding the exposure limit was predicted using a
      mixed-effects logistic model. Concurrent exposures with other occupational
      carcinogens were investigated using the two-step cluster analysis. Results The
      total number of exposure measurements selected was 23 885, with an overall
      arithmetic mean of 0.12 mg/m3. The economic sector with the highest number of
      measurements was manufacturing of chemicals (18 744). The most predictive
      variables of the exposure level resulted to be the occupational group and its
      interaction with the measurement year. The highest likelihood of exceeding the
      exposure limit was found in the manufacture of coke and refined petroleum
      products. Concurrent exposures were frequently detected, mainly with benzene,
      acrylonitrile and ethylene dichloride, and three main clusters were identified.
      Conclusions Exposure to 1,3-butadiene occurs in a wide variety of activity
      sectors and occupational groups. The use of several statistical analysis methods
      applied to occupational exposure databases can help to identify exposure
      situations at high risk for workers' health and better target preventive
      interventions and research projects.

PMID- 28489220
TI  - Transition from Pediatric to Adult Care Is So Important and Challenging.

PMID- 28489221
TI  - Addressing Eating Disorders and Weight Control in Children and Adolescents.
AB  - How often do we look at a patient's body mass index (BMI) and only make a comment
      if the BMI is above normal in the overweight or obese category? As pediatricians,
      we often do not give it a second thought when the BMI is normal, and we generally
      do not counsel on healthy eating practices in these cases. However, when people
      are overweight, obese, and sometimes even normal weight they are told by family,
      friends, as well as physicians that they need to either not gain any more weight,
      or that they need to lose weight. As clinicians, we should be aware that comments
      like that may trigger a disordered pattern of eating for some people, which can
      lead to an eating disorder. [Pediatr Ann. 2017;46(5):176-e179.].

PMID- 28489222
TI  - Transition Medicine-From Pediatric to Adult Care: Part 1.

PMID- 28489223
TI  - A Review of Interventions Aimed at Facilitating Successful Transition Planning
      and Transfer to Adult Care Among Youth with Chronic Illness.
AB  - This article reviews studies that developed interventions aimed at facilitating
      the transition process and/or the transfer of youth with chronic illness to adult
      programs during the past decade. Three key intervention approaches have been
      studied. Data assessing the impact of transition coordinators suggest that the
      most successful outcomes occur when coordinators meet with patients prior to the
      transfer of care, support them as they negotiate the adult programs, and
      facilitate appointment keeping. Data assessing the impact of transition clinics
      suggest that the key to positive outcomes is helping patients develop a trusting
      relationship with the adult providers before fully transferring their care to the
      adult clinic. Similar conclusions can be drawn for transition programs, where it
      appears that the opportunity to discuss and plan transition with a pediatric
      provider over time and to meet with both the pediatric and adult providers
      simultaneously are beneficial for facilitating successful transfer to adult care.
      Although aspects of these care processes appear promising for improving
      transition success, this review identifies areas that need further study. We
      argue that studies are needed that examine individual patient and family-focused
      interventions as well as looking at other potential interventions in the health
      care system. [Pediatr Ann. 2017;46(5):e182-e187.].

PMID- 28489225
TI  - Models of Care for Adolescents and Young Adults with Type 1 Diabetes in
      Transition: Shared Medical Appointments and Telemedicine.
AB  - Transitioning through adolescence and young adulthood is challenging, and even
      more so for patients living with a chronic disease such as type 1 diabetes.
      Patients in this age group encounter multiple obstacles to effectively managing
      their diabetes, experience suboptimal glycemic control, face higher rates of
      acute complications, and are often lost to medical follow-up. Comprehensive
      strategies and innovative clinical models are needed to engage this population in
      diabetes medical care, address barriers to ideal management, and improve
      outcomes. Telemedicine, shared medical appointments (SMA), or a combination of
      telemedicine and SMA are potential models to more successfully, efficiently, and
      satisfactorily address the urgent need for improved care in this high-risk
      population. This article reviews various clinical care models within these
      categories of telemedicine and SMA. [Pediatr Ann. 2017;46(5):e193-e197.].

PMID- 28489224
TI  - Current Concepts of Transition of Care in Cystic Fibrosis.
AB  - Over the past 6 decades, advances in cystic fibrosis (CF) diagnosis and
      management have extended the life expectancy of patients far beyond childhood;
      therefore, all pediatric CF patients must prepare for transition to adult care.
      Readiness assessment, knowledge and skill education, and support structures are
      all elements of ideal transition. Transition should begin early in life with
      teaching skills and knowledge for disease care, and in adolescence the readiness
      to transition should be addressed. Transition is a gradual process of increasing
      responsibilities in self-care and disease management, an improvement in the
      understanding of CF, and an iterative process of self-assessment with knowledge
      acquisition. Communication and collaboration between pediatric and adult
      providers is necessary to ensure a smooth and successful transition with minimum
      effect on outcomes. Although there is increased knowledge of successful
      transition practices, this area presents many opportunities for advancement of
      care for the patient with CF. [Pediatr Ann. 2017;46(5):e188-e192.].

PMID- 28489226
TI  - Transition of Care for Youth with HIV.
AB  - Remarkable advances have been made in the treatment of HIV. Despite progress in
      reducing perinatal HIV transmission, there is a growing number of adolescents and
      emerging adults with HIV who will require transfer of care from pediatric to
      adult providers. Adolescents with HIV have poorer retention in care and viral
      suppression compared to other age groups with HIV. Barriers to successful care of
      youth with HIV include mental health disorders, poor medication adherence,
      socioeconomic instability, and HIV-related stigma. Transfer of care to adult
      providers is often met with reluctance on the part of the adolescent.
      Recommendations for effective transfer of care include clear communication
      between adult and pediatric providers, early initiation of a transition planning
      discussion, a multidisciplinary team approach, and meeting the adult provider
      prior to the transfer of care. Adult HIV care may be more fragmented than
      adolescents are familiar with, but thoughtful transition approaches can foster
      development of health and life skills among youth with HIV. [Pediatr Ann.
      2017;46(5):e198-e202.].

PMID- 28489227
TI  - Using Quality Improvement in Resident Education to Improve Transition Care.
AB  - The importance of a specific transition process is recognized by many health
      organizations. Got Transition, a cooperative endeavor aimed at improving the
      transition from pediatric to adult health care, developed Six Core Elements
      defining the basic components of health care transition support. In this article,
      we review the Six Core Elements by presenting a model that combines resident
      quality improvement and transition care training. In this Internal Medicine
      Pediatrics residency program, ambulatory training for residents takes place in a
      combined adult and pediatric clinic. Aligned with the Six Core Elements, the
      program has crafted and disseminated a transition policy for the practice,
      designed a portable health summary template for the electronic medical record
      (EMR), created EMR tools for assessing transition readiness and setting
      transition goals, formed a registry of patients, and audited charts. [Pediatr
      Ann. 2017;46(5):e203-e206.].

PMID- 28489228
TI  - An Update on Pediatric Pancreatitis.
AB  - There has been a rise in the incidence and number of admissions of children with
      pancreatitis over the past 20 years. Current management practices for
      pancreatitis in children are adapted from standards of care for adults, and there
      are a lack of multicenter, prospective research studies on pancreatitis in
      children. There are inherent differences in the clinical presentation and natural
      course of pancreatitis between adults and children. This review focuses on the
      current understanding of the epidemiology, etiologies, evaluation, and management
      of children with pancreatitis. [Pediatr Ann. 2017;46(5):e207-e211.].

PMID- 28489229
TI  - Regent: An invaluable new offering from the American Academy of Otolaryngology
      Head and Neck Surgery.

PMID- 28489230
TI  - Facial nerve mimicking the fibrocartilaginous annulus of the tympanic membrane.

PMID- 28489231
TI  - A huge parapharyngeal space tumor in a child.

PMID- 28489232
TI  - Elastofibroma.

PMID- 28489233
TI  - Linear IgA dermatosis limited to the mucosal membranes as a rare cause of
      dysphagia.

PMID- 28489234
TI  - The treatment of otorrhea in children with cleft palate: An institutional review.
AB  - We conducted a retrospective observational chart review to characterize otorrhea
      in patients with cleft palate (CP) after tympanostomy tube placement in terms of
      the bacteria profile, treatment effectiveness, and overall disease burden. A
      total of 157 patients over 6 years were reviewed. Fifty of the 157 patients
      (31.8%) experienced postoperative otorrhea. Of the 50 patients with otorrhea, all
      received topical antibiotics, 30 received oral antibiotics, and 12 received
      povidone-iodine irrigations. The average duration of otorrhea was 5.2 months for
      patients with povidone-iodine irrigations and 8.5 months for those without
      povidone-iodine irrigations. Methicillin-resistant Staphylococcus aureus was the
      most commonly cultured microorganism. The average number of total healthcare
      visits over a 12-month period was 13.6 per patient. We conclude that
      postoperative otorrhea is a common problem after tympanostomy tube placement in
      children with CP and places a significant burden on these patients and the
      healthcare system. The bacteriologic profile may be different in this population
      compared with the non-CP population with otorrhea after tympanostomy, and a
      search for more effective treatment options is warranted, including further
      investigation into povidone-iodine irrigations.

PMID- 28489235
TI  - Long-term follow-up of KTP laser turbinate reduction for the treatment of
      obstructive rhinopathy.
AB  - We investigated the subjective, long-term, patient-reported symptom control after
      endoscopic potassium titanyl phosphate (KTP) laser reduction of the inferior
      turbinates. Symptoms were listed preoperatively and patients were asked, via
      telephone interview, the status of their symptoms. Chi-square analysis was used
      to assess statistical significance of the surgical intervention. Thirty-six
      patients (male:female ratio: 5:4) aged 13 to 80 years (mean: 37.2) were available
      for follow-up. The mean follow-up time was 68.47 months (range: 44 to 92). The
      principal symptom patients experienced was nasal obstruction (94.4%);
      postoperative improvement in this symptom at 44 months and beyond was reported by
      85.3% of patients (chi-square 16.94, p < 0.001). Other symptoms, such as
      rhinorrhea and sneezing, showed no significant improvement at long-term follow
      up. This study adds evidence to the long-term improvements in obstructive nasal
      symptoms using KTP laser reduction of the turbinates.

PMID- 28489236
TI  - Histologic correlation of VEGF and COX-2 expression with tumor size in squamous
      cell carcinoma of the larynx and hypopharynx.
AB  - The prognosis and survival of patients with laryngeal and hypopharyngeal squamous
      cell carcinoma (SCC) are related to the clinical staging. Tumor growth and
      metastasis are closely related to angiogenesis. Vascular endothelial growth
      factor (VEGF) and cyclooxygenase 2 (COX-2) are intimately related to the
      angiogenic process in which the blood supply required for neoplastic evolution is
      ensured. Considering the contributions of VEGF and COX-2 to the formation,
      growth, and progression of primary tumors, as well as their metastasis, it has
      been thought that the expression of these two factors might be related to the
      size and/or aggressiveness of laryngeal and hypopharyngeal cancer. To test that
      theory, we conducted a retrospective study to evaluate the expression of VEGF and
      COX-2 markers in archived specimens of SCC of the larynx and hypopharynx to
      correlate their expression with tumor size. These specimens had been obtained
      from 35 patients-31 men and 4 women, aged 37 to 75 years (mean: 57)-who had been
      treated for laryngeal or hypopharyngeal SCC at our tertiary care university
      hospital over a period of 15 years. Immunohistochemical analyses were performed
      with avidin-biotin-peroxidase staining for VEGF and COX-2 antibodies. The degree
      of VEGF and COX-2 expression was based on the German scale of immunoreactivity.
      Specimens were separated into groups based on the intensity of expression
      (none/low and moderate/strong) and tumor size (TNM categories T1/T2 and T3/T4). A
      total of 7 patients exhibited moderate or strong VEGF expression (3 from the
      T1/T2 group and 4 from the T3/T4 group), and 17 patients demonstrated moderate or
      strong COX-2 expression (8 from the T1/T2 group and 9 from the T3/T4 group). We
      found no statistically significant relationship between tumor size and either
      VEGF or COX-2 expression. Our study demonstrated that despite the intrinsic
      connection between and VEGF and COX-2, neither appears to be related to the size
      of the SCCs of the larynx or hypopharynx. Other factors must be involved in the
      pathogenesis and progression of this disease, and further studies are needed to
      identify them.

PMID- 28489237
TI  - Medially displaced common and internal carotid arteries presenting as a pulsatile
      mass: Clinicoradiologic analysis of 62 cases.
AB  - We conducted a prospective study to analyze the medially displaced courses of the
      common carotid artery (CCA) and the cervical segment of the internal carotid
      artery (ICA) in patients who were diagnosed with a pulsatile mass on
      nasopharyngolaryngoscopy and by clinicoradiologic findings. Our study group was
      made up of 62 patients-40 women and 22 men, aged 30 to 88 years (mean: 63.7)-who
      presented with a submucosal pseudomass or a bulging mass on the pharyngeal wall
      with obvious pulsation. For comparison purposes, we recruited a control group of
      62 consecutively presenting patients who had been admitted to our Neurology
      Department with acute severe headache and who had undergone CT angiography based
      on a suspicion of an aneurysm or a vertebral or carotid artery dissection. A
      medially displaced carotid artery was identified in all patients in the study
      group. Two main course abnormalities were observed: (1) a pharyngeal superficial
      placement (PSP), consisting of a bulging or placement immediately adjacent to the
      naso-orohypopharyngeal lumen, and (2) a retropharyngeal midline placement (RMP),
      which entailed medialization of the carotid arteries to the midline. A PSP was
      observed in 11 patients, an RMP was found in 17 patients, and both were seen in
      34 patients. The distance from the aberrant carotid artery to the pharyngeal wall
      and to the retropharyngeal midline of the retropharynx was measured at four
      levels: nasopharyngeal, retropalatal, retroglossal, and retroepiglottic in both
      groups. The mean distance was significantly shorter in the study group than in
      the control group at all four levels (p < 0.002). We conclude that the most
      likely diagnosis of a pulsatile mass detected on nasopharyngolaryngoscopy is an
      aberrant CCA or cervical ICA.

PMID- 28489238
TI  - Quality-of-life outcomes in Graves disease patients after total thyroidectomy.
AB  - Historically, research into surgical treatment of Graves disease has assessed
      subtotal rather than total thyroidectomy. Most clinicians now recommend total
      thyroidectomy, but little information is available regarding quality-of-life
      (QOL) outcomes for this procedure. Our aim was to assess QOL after total
      thyroidectomy. This is a retrospective, pilot study of patients with Graves
      disease who underwent total thyroidectomy from 1991 to 2007 at a high-volume
      tertiary referral center in Toronto, Canada. Questionnaires addressing disease
      specific symptoms and global QOL concerns were sent to 54 patients. Analyses
      included parametric and nonparametric tests to assess the differences between
      perception of symptoms and global QOL before and after surgery. Forty patients
      responded (response rate: 74%) at a median of 4.8 years postoperatively. On a 10
      point scale, overall wellness improved from 4.1 preoperatively to 8.7
      postoperatively (p < 0.001). Patients recalled missing less work or school after
      surgery (7.8 vs. 1.1 days/year; p = 0.001). Overall satisfaction with the
      procedure was high. On average, symptoms improved within 32 days of surgery, and
      all symptoms showed substantial improvement. This is the first North American
      study to assess QOL outcomes of patients with Graves disease after total
      thyroidectomy. Patients experienced marked and rapid improvement in QOL
      postoperatively. These findings suggest that total thyroidectomy is a safe and
      effective treatment.

PMID- 28489239
TI  - Therapeutic effect of hyaluronic acid in reducing nasal mucosa recovery time
      after septoplasty.
AB  - Mucociliary clearance represents a host defense mechanism of airways that can be
      compromised by various pathologic conditions, such as nasal septal deviation.
      Although septoplasty can resolve obstruction, it impairs mucociliary clearance in
      the immediate postoperative period. Clinical studies have demonstrated how
      hyaluronic acid can interfere with this function. Our study aims to provide
      evidence of a therapeutic effect of hyaluronic acid on nasal mucosa recovery
      after septoplasy. Sixty-five patients underwent septoplasty. On postoperative day
      1, patients were randomized to a control arm that was treated with mupirocin
      ointment or an experimental arm that received additional treatment with sodium
      hyaluronate solution. Pre- and postoperatively, anterior rhinoscopy was performed
      to analyze mucosal status, and mucociliary clearance was measured by using the
      saccharin transit time (STT) method. The t test was used for independent groups.
      During the preoperative evaluation, we observed a significant difference in STT
      between the convex and concave side in both groups. Fifteen days after surgery,
      we observed a significant difference preoperatively to postoperatively for both
      the convex and the concave side (p < 0.02 and p < 0.008, respectively). One month
      after surgery, we observed a reduction of STT when comparing preoperative control
      group values and, after 1 month, postoperative values in both sides (p < 0.015
      and p < 0.005, convex and concave side, respectively). Our results show a
      significant reduction of the STT for both nasal sides as soon as 15 days after
      septoplasty in patients randomized to additional treatment. Our experience
      provides further evidence for the therapeutic effect of hyaluronic acid in
      accelerating nasal mucosa recovery after septoplasty.

PMID- 28489240
TI  - The role of hypertonic saline in monopolar tonsillectomy in adult patients.
AB  - This study's objective was to look for a simple and inexpensive method to reduce
      patients' pain during tonsillectomy. Bilateral tonsillectomy patients were
      enrolled and placed into different groups based on their admission numbers.
      Patients with odd numbers had electrical tonsillectomy on the right side with
      hypertonic saline injection into the tonsillar capsule (group A) or electrical
      tonsillectomy on the left side with normal saline injection (group B). Those with
      even numbers had electrical tonsillectomy on the left side with hypertonic saline
      injection into the tonsillar capsule (group A) or electrical tonsillectomy on the
      right side with normal saline injection (group B). Pain, operative bleeding,
      postoperative bleeding, and operation time were evaluated. Injecting hypertonic
      saline into the tonsillar capsule reduced pain caused by electrical tonsillectomy
      but did not impact the operative or postoperative bleeding and operation time.
      While simple and economic, monopolar electrical tonsillectomy with the help of
      hypertonic saline injected into the tonsillar capsule can effectively relieve
      patients' pain when compared to surgeries with normal saline injection.

PMID- 28489241
TI  - In-office vs. operating room procedures for recurrent respiratory papillomatosis.
AB  - We conducted a study to analyze hospital and patient costs, outcomes, and patient
      satisfaction among adults undergoing in-office and operating room procedures for
      the treatment of recurrent respiratory papillomatosis. Our final study population
      was made up of 17 patients-1 man and 16 women, aged 30 to 86 years (mean: 62).
      The mean number of in-office laser procedures per patient was 4.2, and the mean
      interval between procedures was 5.4 months (although 10 patients underwent only 1
      office procedure); the mean number of operating room procedures was 13.5, and the
      mean interval between procedures was 14.3 months. An equal number of patients
      reported complications or adverse events with the two types of procedures-5 each.
      The difference in cost between the office procedure (mean: $3,413.00) and the
      operating room procedure (mean: $12,382.59) was almost $9,000, but these savings
      were offset by the fact that the office procedures needed to be performed three
      times as often. Patients reported slightly more anxiety and discomfort during the
      office procedures and, overall, they appeared to prefer the operating room
      procedure. We conclude that office procedures are significantly more cost
      effective than operating room procedures, but their use may be limited by patient
      tolerance and the increased frequency of the procedure.

PMID- 28489242
TI  - Large pediatric maxillary dentigerous cysts presenting with sinonasal and orbital
      symptoms: A case series.
AB  - Dentigerous cysts are benign odontogenic cysts associated with the crowns of
      unerupted, embedded, or impacted teeth. Most of them are associated with
      mandibular third molars, followed by maxillary third molars and canines. They are
      usually asymptomatic, and rarely do they grow extensively and compress the
      adjacent anatomic structures. We report 5 cases of extensive maxillary
      dentigerous cysts presenting with sinonasal and orbital symptoms. A literature
      review for similar presentations of dentigerous cysts has demonstrated 21 cases.
      Recognition of the extensive growth potential of the dentigerous cyst, diagnosing
      it with its unusual presentation, and appropriate management are discussed in
      this article.

PMID- 28489243
TI  - Nasal, pharyngeal, and laryngeal pemphigus vulgaris successfully treated with
      rituximab.
AB  - Pemphigus vulgaris is a potentially fatal autoimmune blistering disease that can
      involve the nasopharyngeal and laryngeal tissues. The disease can be recalcitrant
      to conventional oral treatments, and treatment alternatives are limited. This
      retrospective study evaluated the efficacy of rituximab as a rescue agent in 5
      patients with recalcitrant pemphigus vulgaris involving nasopharyngeal and
      laryngeal mucosa. All 5 patients were unresponsive to systemic steroids and at
      least one conventional oral immunosuppressive agent. The patients received
      rituximab infusions as a rescue agent because of recalcitrant disease. All 5
      patients had a complete clinical response to rituximab and could discontinue
      systemic steroids and reduce the dosage of their initial immunosuppressive agent.
      No major adverse reactions were observed or reported with rituximab. Rituximab
      can be used as an effective rescue agent in the treatment of severe pemphigus
      vulgaris with nasopharyngeal and laryngeal involvement.

PMID- 28489244
TI  - Role of intraoperative ropivacaine in adult post-tonsillectomy pain control: A
      randomized controlled trial.
AB  - We sought to evaluate the efficacy of ropivacaine in post-tonsillectomy pain
      management in adults and evaluate the timing of intraoperative ropivacaine
      administration for this purpose. A prospective, double-blinded, randomized,
      controlled trial with a paired design was performed in 25 consecutive adults
      undergoing tonsillectomy. To date, no studies examining the efficacy of local
      anesthetics in post-tonsillectomy pain control have used a paired design to
      account for the variability in pain difference between individuals. Patients were
      prerandomized into those receiving tonsillar fossa injections before or after the
      tonsillectomy. All surgeries were performed by the senior author. The tonsil on 1
      side was injected with saline and the tonsil on the other side with ropivacaine.
      Patient responses were obtained via written questionnaire. Three of 25 patients
      were excluded from the study. Sixteen of 22 patients had lateralization of pain
      to 1 side during recovery. No statistically significant difference in pain
      control was observed between ropivacaine and normal saline. Local anesthetic
      decreased pain in 7 of 22 patients, and increased pain was experienced on the
      side with local anesthetic in 9 of 22 patients. Six of 22 patients had no
      difference in pain from one side to the other. The time to equalization of pain
      based on laterality was 8.8 and 6.8 days, respectively, in the patients injected
      before or immediately after the tonsillectomy. Administration of the local
      anesthetic ropivacaine does not affect post-tonsillectomy pain. Moreover, timing
      of injection does not affect postoperative pain. We recommend against the use of
      intraoperative ropivacaine for pain control in patients undergoing tonsillectomy.

PMID- 28489245
TI  - Stapes-pyramidal fixation by a bony bar [Letter].

PMID- 28489246
TI  - Atypical presentation of vocal fold granulomas.

PMID- 28489247
TI  - Endoscopic view of long-term patency of the sphenoid ostium following balloon
      dilation.

PMID- 28489248
TI  - Intact FGF23 and alpha-klotho during acute inflammation/sepsis in CKD patients.

PMID- 28489249
TI  - Validation of two prognostic models for recurrence and survival after radical
      gastrectomy for gastric cancer.
AB  - BACKGROUND: Prognostic models from Korea and Italy have been developed that
      predict overall survival and cancer recurrence respectively after radical
      gastrectomy for gastric cancer. The aim of this study was to validate the two
      models in independent patient cohorts, and to evaluate which factors may explain
      differences in prognosis between Korean and Italian patients with gastric cancer.
      METHODS: Patients who underwent radical gastrectomy for gastric cancer between
      January 2000 and December 2004 at Seoul National University Hospital and at eight
      centres in Italy were included. Discrimination of the models was tested with
      receiver operating characteristic (ROC) curves and calculation of area under the
      curve (AUC). Calibration was evaluated by plotting actual survival probability
      against predicted survival probability for the Korean nomogram, and actual
      against predicted risk of recurrence for the Italian score. RESULTS: Some 2867
      and 940 patients from Korea and Italy respectively were included. The Korean
      nomogram achieved good discrimination in the Italian cohort (AUC 0.80, 95 per
      cent c.i. 0.77 to 0.83), and the Italian model performed well in the Korean
      cohort (AUC 0.87, 0.85 to 0.89). The Korean nomogram also achieved good
      calibration, but this was not seen for the Italian model. Multivariable analyses
      confirmed that Italian ethnicity was an independent risk factor for cancer
      recurrence (odds ratio (OR) 1.72, 1.31 to 2.25; P < 0.001), but not for overall
      survival (OR 1.20, 0.95 to 1.53; P = 0.130). CONCLUSION: Both prognostic models
      performed fairly well in independent patient cohorts. Differences in recurrence
      rates of gastric cancer may be partially explained by ethnicity.

PMID- 28489251
TI  - Geographically structured genetic variation in the Medicago lupulina-Ensifer
      mutualism.
AB  - Gene flow between genetically differentiated populations can maintain variation
      in species interactions, especially when population structure is congruent
      between interacting species. However, large-scale empirical comparisons of the
      population structure of interacting species are rare, particularly in positive
      interspecific interactions (mutualisms). One agriculturally and ecologically
      important mutualism is the partnership between legume plants and rhizobia.
      Through characterizing and comparing the population genomic structure of the
      legume Medicago lupulina and two rhizobial species (Ensifer medicae and E.
      meliloti), we explored the spatial scale of population differentiation between
      interacting partners in their introduced range in North America. We found high
      proportions of E. meliloti in southeastern populations and high proportions of E.
      medicae in northwestern populations. Medicago lupulina and the Ensifer genus
      showed similar patterns of spatial genetic structure (isolation by distance).
      However, we detected no evidence of isolation by distance or population structure
      within either species of bacteria. Genome-wide nucleotide diversity within each
      of the two Ensifer species was low, suggesting limited introduction of strains,
      founder events, or severe bottlenecks. Our results suggest that there is
      potential for geographically structured coevolution between M. lupulina and the
      Ensifer genus, but not between M. lupulina and either Ensifer species.

PMID- 28489250
TI  - Causal mechanisms of soil organic matter decomposition: deconstructing salinity
      and flooding impacts in coastal wetlands.
AB  - Coastal wetlands significantly contribute to global carbon storage potential. Sea
      level rise and other climate-change-induced disturbances threaten coastal wetland
      sustainability and carbon storage capacity. It is critical that we understand the
      mechanisms controlling wetland carbon loss so that we can predict and manage
      these resources in anticipation of climate change. However, our current
      understanding of the mechanisms that control soil organic matter decomposition,
      in particular the impacts of elevated salinity, are limited, and literature
      reports are contradictory. In an attempt to improve our understanding of these
      complex processes, we measured root and rhizome decomposition and developed a
      causal model to identify and quantify the mechanisms that influence soil organic
      matter decomposition in coastal wetlands that are impacted by sea-level rise. We
      identified three causal pathways: (1) a direct pathway representing the effects
      of flooding on soil moisture, (2) a direct pathway representing the effects of
      salinity on decomposer microbial communities and soil biogeochemistry, and (3) an
      indirect pathway representing the effects of salinity on litter quality through
      changes in plant community composition over time. We used this model to test the
      effects of alternate scenarios on the response of tidal freshwater forested
      wetlands and oligohaline marshes to short- and long-term climate-induced
      disturbances of flooding and salinity. In tidal freshwater forested wetlands, the
      model predicted less decomposition in response to drought, hurricane salinity
      pulsing, and long-term sea-level rise. In contrast, in the oligohaline marsh, the
      model predicted no change in response to drought and sea-level rise, and
      increased decomposition following a hurricane salinity pulse. Our results show
      that it is critical to consider the temporal scale of disturbance and the
      magnitude of exposure when assessing the effects of salinity intrusion on carbon
      mineralization in coastal wetlands. Here, we identify three causal mechanisms
      that can reconcile disparities between long-term and short-term salinity impacts
      on organic matter decomposition.

PMID- 28489252
TI  - Social effects for locomotion vary between environments in Drosophila
      melanogaster females.
AB  - Despite strong purifying or directional selection, variation is ubiquitous in
      populations. One mechanism for the maintenance of variation is indirect genetic
      effects (IGEs), as the fitness of a given genotype will depend somewhat on the
      genes of its social partners. IGEs describe the effect of genes in social
      partners on the expression of the phenotype of a focal individual. Here, we ask
      what effect IGEs, and variation in IGEs between abiotic environments, has on
      locomotion in Drosophila. This trait is known to be subject to intralocus
      sexually antagonistic selection. We estimate the coefficient of interaction, Psi,
      using six inbred lines of Drosophila. We found that Psi varied between abiotic
      environments, and that it may vary across among male genotypes in an abiotic
      environment specific manner. We also found evidence that social effects of males
      alter the value of a sexually dimorphic trait in females, highlighting an
      interesting avenue for future research into sexual antagonism. We conclude that
      IGEs are an important component of social and sexual interactions and that they
      vary between individuals and abiotic environments in complex ways, with the
      potential to promote the maintenance of phenotypic variation.

PMID- 28489253
TI  - Randomized clinical trial comparing collagen plug and advancement flap for trans
      sphincteric anal fistula.
AB  - BACKGROUND: The role of a collagen plug for treating anal fistula is not well
      established. A randomized prospective multicentre non-inferiority study of
      surgical treatment of trans-sphincteric cryptogenic fistulas was undertaken,
      comparing the anal fistula plug with the mucosal advancement flap with regard to
      fistula recurrence rate and functional outcome. METHODS: Patients with an anal
      fistula were evaluated for eligibility in three centres, and randomized to either
      mucosal advancement flap surgery or collagen plug, with clinical follow-up at 3
      and 12 months. The primary outcome was the fistula recurrence rate. Anal pain
      (visual analogue scale), anal incontinence (St Mark's score) and quality of life
      (Short Form 36 questionnaire) were also reported. RESULTS: Ninety-four patients
      were included; 48 were allocated to the plug procedure and 46 to advancement flap
      surgery. The median follow-up was 12 (range 9-24) months. The recurrence rate at
      12 months was 66 per cent (27 of 41 patients) in the plug group and 38 per cent
      (15 of 40) in the flap group (P = 0.006). Anal pain was reduced after operation
      in both groups. Anal incontinence did not change in the follow-up period.
      Patients reported an increased quality of life after 3 months. There were no
      differences between the groups with regard to pain, incontinence or quality of
      life. CONCLUSION: There was a considerably higher recurrence rate after the anal
      fistula plug procedure than following advancement flap repair. Registration
      number: NCT01021774 (http://www.clinicaltrials.gov).

PMID- 28489254
TI  - Use of intra-aortic counterpulsation in cardiogenic shock post-liver
      transplantation.
AB  - Left ventricular dysfunction resulting in cardiogenic shock occurs infrequently
      following organ reperfusion in liver transplantation. The etiology of the
      cardiogenic shock is often multifactorial and difficult to manage due to the
      complex nature of the procedure and the patient's baseline physiology.
      Traditionally, this hemodynamic instability is managed medically using inotropic
      agents and vasopressor support. If medical treatment is insufficient, the use of
      an intra-aortic balloon pump for counterpulsation may be employed to improve the
      hemodynamics and stabilize the patient. Here, we analyze three cases and review
      the literature.

PMID- 28489255
TI  - Increased risk of portal vein thrombosis in patients with autoimmune hepatitis on
      the liver transplantation waiting list.
AB  - Liver transplantation (LT) is indicated in autoimmune hepatitis (AIH) for both
      acute presentation with liver failure and end-stage chronic liver disease. Few
      studies have suggested an association between AIH and coagulation disorders and a
      higher incidence of portal vein thrombosis (PVT) in patients with AIH listed for
      LT. The aim of this study was to determine the incidence of thrombotic
      complications, particularly PVT, in a cohort of 37 patients undergoing LT because
      of AIH. PVT was present before transplantation in 30% (n=11) of these patients
      compared to 11% in the whole population transplanted in our center (P=.002). On
      comparing only patients with cirrhosis, PVT was present in 55% of the AIH group,
      being 12% in the whole cohort (P<.001). Among patients with PVT before LT, no
      patient receiving anticoagulation therapy early after LT developed recurrence of
      PVT, whereas two patients (33%) without anticoagulation therapy did. The
      increased incidence of PVT in the pretransplant period and the possibility of
      thrombosis recurrence after LT suggest that patients with AIH and PVT could
      benefit from anticoagulation therapy after transplantation. However, further
      studies are needed to recommend anticoagulation in these patients in clinical
      practice.

PMID- 28489256
TI  - Clinical and virologic outcomes in high-risk adult Epstein-Barr virus mismatched
      organ transplant recipients.
AB  - Epstein-Barr virus (EBV) D+/R- organ transplant recipients are a high-risk group
      for developing post-transplant lymphoproliferative disease (PTLD). Little data
      are available for prevention in the adult EBV mismatched population. We conducted
      a retrospective study of EBV D+/R- organ transplants performed during 2002-2014.
      Of the 153 patients identified, 82.4% patients received antiviral prophylaxis
      with valganciclovir for a median of 4.5 months (range: 0.8-22 months) and 36.6%
      underwent viral load monitoring in the first post-transplant year. EBV viremia
      developed in 67.2% monitored patients. In viremic patients, immunosuppression was
      reduced in 20/37(54.1%) in response to viremia and 17/37 (45.9%) received
      therapeutic dose valganciclovir. In patients with EBV viremia who received
      valganciclovir and/or had a reduction in immunosuppression and had sufficient
      viral load time points (n=31), 28 (90.3%) had a significant decline in viral load
      at day 14 (median log decline 0.49 (0.24-0.64), P<.001) and at day 30 (0.87 (0.52
      1.21), P<.001). PTLD developed in 27 (15%) patients (biopsy proven=25,
      possible=2) at median 8 months (range: 2.4-130) post-transplant with the majority
      (81.5%) within the first year. In multivariate analysis, viral load monitoring
      and use of mycophenolate were associated with a lower incidence of PTLD.
      Antiviral prophylaxis was not associated with a lower risk of PTLD, but viral
      load monitoring and use of mycophenolate mofetil were protective.

PMID- 28489258
TI  - Triggered and Tunable Hydrogen Sulfide Release from Photogenerated
      Thiobenzaldehydes.
AB  - Hydrogen sulfide (H2 S) has been identified as an important cell-signaling
      mediator and has a number of biological functions, such as vascular smooth muscle
      relaxation, neurotransmission, and regulation of inflammation. A facile and
      versatile approach for H2 S production initiated by light irradiation and
      controlled by reaction with an amine or an amino acid was developed. The donor
      was synthesized in a one-pot reaction, and simple crystallization led to a yield
      of approximately 90 %. The synthetic strategy is scalable and versatile, and the
      H2 S donors can be expressed ina number of different molecular and macromolecular
      forms, including crystalline small-molecule compounds, water-soluble polymers,
      polystyrene films, and hydrogels. The H2 S donors based on polystyrene film and
      hydrogel were used as cell-culture scaffolds. The H2 S donor based on water
      soluble polymer was applied in photocontrolled inhibition of P-selectin
      expression on human platelets and subsequent regulation of platelet aggregation.
      This study provides the simplest controllable H2 S source to study its biological
      functions. The developed materials are also new therapeutic platforms to deliver
      H2 S, as there is no accumulation of toxic byproducts, and the donor materials
      from polystyrene films and hydrogels can be readily removed after releasing H2 S.

PMID- 28489257
TI  - Unsaturated Long-Chain Fatty Acids Are Preferred Ferritin Ligands That Enhance
      Iron Biomineralization.
AB  - Ferritin is a ubiquitous nanocage protein, which can accommodate up to thousands
      of iron atoms inside its cavity. Aside from its iron storage function, a new role
      as a fatty acid binder has been proposed for this protein. The interaction of apo
      horse spleen ferritin (HoSF) with a variety of lipids has been here investigated
      through NMR spectroscopic ligand-based experiments, to provide new insights into
      the mechanism of ferritin-lipid interactions, and the link with iron
      mineralization. 1D 1 H, diffusion (DOSY) and saturation-transfer difference (STD)
      NMR experiments provided evidence for a stronger interaction of ferritin with
      unsaturated fatty acids compared to saturated fatty acids, detergents, and bile
      acids. Mineralization assays showed that oleate c aused the most efficient
      increase in the initial rate of iron oxidation, and the highest formation of
      ferric species in HoSF. The comprehension of the factors inducing a faster
      biomineralization is an issue of the utmost importance, given the association of
      ferritin levels with metabolic syndromes, such as insulin resistance and
      diabetes, characterized by fatty acid concentration dysregulation. The human
      ferritin H-chain homopolymer (HuHF), featuring ferroxidase activity, was also
      tested for its fatty acid binding capabilities. Assays show that oleate can bind
      with high affinity to HuHF, without altering the reaction rates at the
      ferroxidase site.

PMID- 28489259
TI  - Molecular alterations in odontogenic keratocysts as potential therapeutic
      targets.
AB  - The odontogenic keratocyst (OKC) is a cystic lesion, lined by uniformly thickened
      parakeratinized epithelium. Some lesions are large and tend to recur after
      surgical treatment. The neoplastic nature of OKCs remains a matter of dispute. It
      is known that some sporadic OKCs harbor PTCH1 mutations, and via the dissection
      of cyst epithelium, these mutations were demonstrated to occur much more
      frequently than previously thought. In addition to the classical PTCH1 mutations,
      Hedgehog pathway disturbance and Bcl-2 protein overexpression, as detected via
      genome-wide expression analysis of OKCs, have been published. Changes in DNA
      methylation patterns and alterations in microRNA expression levels have recently
      been reported in these lesions. We reviewed the molecular mechanisms that
      underlie the pathogenesis of OKCs as described over the past few years and
      explored the molecular alterations that can be therapeutically targeted.

PMID- 28489261
TI  - C-N Bond Activation and Ring Opening of a Saturated N-Heterocyclic Carbene by
      Lateral Alkali-Metal-Mediated Metalation.
AB  - Combining alkali-metal-mediated metalation (AMMM) and N-heterocyclic carbene
      (NHC) chemistry, a novel C-N bond activation and ring-opening process is
      described for these increasingly important NHC molecules, which are generally
      considered robust ancillary ligands. Here, mechanistic investigations on
      reactions of saturated NHC SIMes (SIMes=[:C{N(2,4,6-Me3 C6 H2 )CH2 }2 ]) with
      Group 1 alkyl bases suggest this destructive process is triggered by lateral
      metalation of the carbene. Exploiting co-complexation and trans-metal-trapping
      strategies with lower polarity organometallic reagents (Mg(CH2 SiMe3 )2 and
      Al(TMP)iBu2 ), key intermediates in this process have been isolated and
      structurally defined.

PMID- 28489260
TI  - Histologic changes associated with talaporfin sodium-mediated photodynamic
      therapy in rat skin.
AB  - BACKGROUND AND OBJECTIVE: Alternative treatments are needed to achieve consistent
      and more complete port wine stain (PWS) removal, especially in darker skin types;
      photodynamic therapy (PDT) is a promising alternative treatment. To this end, we
      previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to
      understand treatment tissue effects to design a protocol that will achieve
      selective vascular injury without ulceration and scarring. The objective of this
      work is to assess skin changes associated with TS-mediated PDT with clinically
      relevant treatment parameters. STUDY DESIGN/MATERIALS AND METHODS: We performed
      TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures
      were varied between 15 and 100 J/cm2 . We took skin biopsies from subjects at 9
      hours following PDT. We assessed the degree and depth of vascular and surrounding
      tissue injury using histology and immunohistochemical staining. RESULTS: TS
      mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm2 light doses resulted in
      vascular injury with minimal epidermal damage. At light dose of 50 J/cm2 ,
      epidermal damage was noted with vascular injury. At light doses >50 J/cm2 , both
      vascular and surrounding tissue injury were observed in the forms of vasculitis,
      extravasated red blood cells, and coagulative necrosis. Extensive coagulative
      necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm2
      light doses. Observed depth of injury increased with increasing radiant exposure,
      although this relationship was not linear. CONCLUSION: TS-mediated PDT can cause
      selective vascular injury; however, at higher light doses, significant extra
      vascular injury was observed. This information can be used to contribute to
      design of safe protocols to be used for treatment of cutaneous vascular lesions.
      Lasers Surg. Med. 49:767-772, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28489262
TI  - Mechanochemical Friedel-Crafts Alkylation-A Sustainable Pathway Towards Porous
      Organic Polymers.
AB  - This study elucidates an innovative mechanochemical approach applying Friedel
      Crafts alkylation to synthesize porous covalent triazine frameworks (CTFs).
      Herein, we pursue a counterintuitive approach by utilizing a rather destructive
      method to synthesize well-defined materials with intrinsic porosity.
      Investigating a model system including carbazole as monomer and cyanuric chloride
      as triazine node, ball milling is shown to successfully yield porous polymers
      almost quantitatively. We verified the successful structure formation by an in
      depth investigation applying XPS, solid-state NMR and FT-IR spectroscopy. An in
      situ study of pressure and temperature developments inside the milling chamber in
      combination with two-dimensional liquid-state NMR spectroscopy reveals insights
      into the polymerization mechanism. The versatility of this mechanochemical
      approach is showcased by application of other monomers with different size and
      geometry.

PMID- 28489263
TI  - Diagnostic anoctamin-5 protein defect in patients with ANO5-mutated muscular
      dystrophy.
AB  - AIMS: Previously, detection of ANO5 protein has been complicated by unspecific
      antibodies, most of which have not identified the correct protein. The aims of
      the study were to specify ANO5 protein expression in human skeletal muscle, and
      to investigate if the ANO5 protein levels are affected by different ANO5
      mutations in anoctaminopathy patients. METHODS: Four different antibodies were
      tested for ANO5 specificity. A sample preparation method compatible with membrane
      proteins, combined with tissue fractionation was used to determine ANO5
      expression in cell cultures expressing ANO5, in normal muscles and eight patient
      biopsies with six different ANO5 mutations in homozygous or compound heterozygous
      states, and in other dystrophies. RESULTS: Only one specific monoclonal N
      terminal ANO5 antibody was efficient in detecting the protein, showing that ANO5
      is expressed as a single 107 kD polypeptide in human skeletal muscle. The
      truncating mutations c.191dupA and c.1261C>T were found to abolish ANO5
      expression, whereas the studied point mutations had variable effects; however,
      all the ANO5 mutations resulted in clearly reduced ANO5 expression in the patient
      muscle membrane fraction. Attempts to detect ANO5 using immunohistochemistry were
      not yet successful. CONCLUSIONS: The data presented here indicate that the ANO5
      protein expression is decreased in ANO5-mutated muscular dystrophy and that most
      of the non-truncating pathogenic ANO5 mutations likely destabilize the protein
      and cause its degradation. The method described here allows direct analysis of
      human ANO5 protein, which can be used in diagnostics, for evaluating the
      pathogenicity of the potentially harmful ANO5 variants of uncertain significance.

PMID- 28489264
TI  - Critical factors for the recovery of marine mammals.
AB  - {en} Over the past decades, much research has focused on understanding the
      critical factors for marine extinctions with the aim of preventing further
      species losses in the oceans. Although conservation and management strategies are
      enabling several species and populations to recover, others remain at low
      abundance levels or continue to decline. To understand these discrepancies, we
      used a published database on abundance trends of 137 populations of marine
      mammals worldwide and compiled data on 28 potentially critical factors for
      recovery. We then applied random forests and additive mixed models to determine
      which intrinsic and extrinsic factors are critical for the recovery of marine
      mammals. A mix of life-history characteristics, ecological traits, phylogenetic
      relatedness, population size, geographic range, human impacts, and management
      efforts explained why populations recovered or not. Consistently, species with
      lower age at maturity and intermediate habitat area were more likely to recover,
      which is consistent with life-history and ecological theory. Body size, trophic
      level, social interactions, dominant habitat, ocean basin, and habitat
      disturbance also explained some differences in recovery patterns. Overall, a
      variety of intrinsic and extrinsic factors were important for species' recovery,
      pointing to cumulative effects. Our results provide insight for improving
      conservation and management strategies to enhance recoveries in the future.

PMID- 28489265
TI  - Isolation of Azadiphosphiridines and Diphosphenimines by Cycloaddition of Azides
      and a Cationic Diphosphene.
AB  - The polarized, cationic diphosphene [(Cl ImDipp )P=P(Dipp)]+ as the triflate salt
      7[OTf](Cl ImDipp =4,5-dichloro-1,3-bis(Dipp)-imidazol-2-yl; Dipp=2,6
      diisopropylphenyl) reacts with azides of type RN3 (R=Dipp or Dmp; Dmp=2,5
      dimethylphenyl) in a [2+3] cycloaddition reaction followed by the release of N2
      and a subsequent electrocyclic ring-closing reaction to azadiphosphiridine salts
      [(Cl ImDipp )P-P(Dipp)-N(R)]10a,b[OTf] (R=Dipp or Dmp). The reaction of 7[X]
      (X=OTf, GaCl4 ) with the electron-rich azides Me3 SiN3 and NaN3 give the unusual
      diphosphenimine derivatives [(Cl ImDipp )P-P(Dipp)=N(SiMe3 )]+ (11[OTf]) and [(Cl
      ImDipp )P-P(Dipp)=N(GaCl3 )] (12), respectively, featuring an acyclic P2 N
      moiety. Theoretical calculations provide insights into the reaction mechanisms to
      the cyclic and acyclic forms, in which the thermodynamic stability of the latter
      prevents the electrocyclic ring closure.

PMID- 28489266
TI  - Redox-Sensitive Stomatocyte Nanomotors: Destruction and Drug Release in the
      Presence of Glutathione.
AB  - The development of artificial nanomotor systems that are stimuli-responsive is
      still posing many challenges. Herein, we demonstrate the self-assembly of a redox
      responsive stomatocyte nanomotor system, which can be used for triggered drug
      release under biological reducing conditions. The redox sensitivity was
      introduced by incorporating a disulfide bridge between the hydrophilic
      poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated
      with the endogenous reducing agent glutathione at a concentration comparable to
      that within cells, the external PEG shells of these stimuli-responsive nanomotors
      are cleaved. The specific bowl-shaped stomatocytes aggregate after the treatment
      with glutathione, leading to the loss of motion and triggered drug release. These
      novel redox-responsive nanomotors can not only be used for remote transport but
      also for drug delivery, which is promising for future biomedical applications.

PMID- 28489267
TI  - Visible-Light Photocatalytic Intramolecular Cyclopropane Ring Expansion.
AB  - Described herein is a new visible-light photocatalytic strategy for the synthesis
      of enantioenriched dihydrofurans and cyclopentenes by an intramolecular nitro
      cyclopropane ring expansion reaction. Mechanistic studies and DFT calculations
      are used to elucidate the key factors in this new ring expansion reaction, and
      the need for the nitro group on the cyclopropane.

PMID- 28489268
TI  - Interprotein Electron Transfer between FeS-Protein Nanowires and Oxygen-Tolerant
      NiFe Hydrogenase.
AB  - Self-assembled redox protein nanowires have been exploited as efficient electron
      shuttles for an oxygen-tolerant hydrogenase. An intra/inter-protein electron
      transfer chain has been achieved between the iron-sulfur centers of rubredoxin
      and the FeS cluster of [NiFe] hydrogenases. [NiFe] Hydrogenases entrapped in the
      intricated matrix of metalloprotein nanowires achieve a stable, mediated
      bioelectrocatalytic oxidation of H2 at low-overpotential.

PMID- 28489269
TI  - Digest: For ecologically similar Andean birds, gene flow and plumage uniformity
      go hand in hand.

PMID- 28489270
TI  - Controlled Synthesis of Poly(p-phenylene) Using a Zincate Complex, t Bu4 ZnLi2.
AB  - Well-defined poly(2,5-dihexyloxyphenylene-1,4-diyl) (PPP) is successfully
      synthesized by the Negishi catalyst-transfer polycondensation (NCTP) using
      dilithium tetra(tert-butyl)zincate (t Bu4 ZnLi2 ). The obtained PPP possesses the
      number-averaged molecular weight (Mn ) values in the range of 2100-22 000 and the
      molar-mass dispersity (DM ) values in the range of 1.09-1.23. In addition, block
      copolymers containing PPP and poly(3-hexylthiophene) (P3HT) segments (PPP-b-P3HT)
      are synthesized to confirm the feasibility of chain extension between the
      different monomers based on NCTP.

PMID- 28489271
TI  - Successful Treatment of Kaposi Sarcoma-Associated Herpesvirus Inflammatory
      Cytokine Syndrome After Kidney-Liver Transplant: Correlations With the Human
      Herpesvirus 8 miRNome and Specific T Cell Response.
AB  - After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi
      sarcoma-associated herpesvirus (KSHV) is known to cause aggressive tumors and
      severe nonneoplastic complications. These latter syndromes are driven by HHV
      8/KSHV lytic reactivations and related hyperinflammatory host responses typically
      characterized by high viral loads, elevated levels of cytokines and other
      inflammation biomarkers, cytopenia, organ failure, high fever, and worsening
      conditions (with no evidence of B cell neoplasias). These disorders are
      associated with a high mortality rate, often due to lack of prompt diagnosis,
      effective therapeutic approaches, and adequate follow-up. These features resemble
      most of those defining the so-called KSHV-associated inflammatory cytokine
      syndrome (KICS), which was recently recognized in patients positive for human
      immunodeficiency virus (HIV). In this report, we describe-for the first time-a
      case of a KICS-like nonneoplastic recurrent complication occurring after
      transplant in an HIV-negative patient that was successfully treated by a
      combination of anti-CD20 monoclonal therapy, antivirals, and modification of the
      immunosuppressive regimen. In addition to clinical and laboratory findings
      collected during 3-year follow-up, we report novel experimental data on HHV-8
      specific T cell dynamics and circulating microRNA profile, showing correlations
      with clinical course and other laboratory markers (including viral load, C
      reactive protein, and cytokine levels), providing useful information about
      abnormal cellular and cytokine dynamics underlying HHV-8-associated inflammatory
      disorders in posttransplant patients.

PMID- 28489272
TI  - Fear learning alterations after traumatic brain injury and their role in
      development of posttraumatic stress symptoms.
AB  - BACKGROUND: It is unknown how traumatic brain injury (TBI) increases risk for
      posttraumatic stress disorder (PTSD). One potential mechanism is via alteration
      of fear-learning processes that could affect responses to trauma memories and
      cues. We utilized a prospective, longitudinal design to determine if TBI is
      associated with altered fear learning and extinction, and if fear processing
      mediates effects of TBI on PTSD symptom change. METHODS: Eight hundred fifty two
      active-duty Marines and Navy Corpsmen were assessed before and after deployment.
      Assessments included TBI history, PTSD symptoms, combat trauma and deployment
      stress, and a fear-potentiated startle task of fear acquisition and extinction.
      Startle response and self-reported expectancy and anxiety served as measures of
      fear conditioning, and PTSD symptoms were measured with the Clinician
      Administered PTSD Scale. RESULTS: Individuals endorsing "multiple hit" exposure
      (both deployment TBI and a prior TBI) showed the strongest fear acquisition and
      highest fear expression compared to groups without multiple hits. Extinction did
      not differ across groups. Endorsing a deployment TBI was associated with higher
      anxiety to the fear cue compared to those without deployment TBI. The association
      of deployment TBI with increased postdeployment PTSD symptoms was mediated by
      postdeployment fear expression when recent prior-TBI exposure was included as a
      moderator. TBI associations with increased response to threat cues and PTSD
      symptoms remained when controlling for deployment trauma and postdeployment PTSD
      diagnosis. CONCLUSIONS: Deployment TBI, and multiple-hit TBI in particular, are
      associated with increases in conditioned fear learning and expression that may
      contribute to risk for developing PTSD symptoms.

PMID- 28489273
TI  - Low level light-minoxidil 5% combination versus either therapeutic modality alone
      in management of female patterned hair loss: A randomized controlled study.
AB  - BACKGROUND: Female pattern hair loss (FPHL) is the most common form of hair loss
      in women. Nevertheless, its management represents a real challenge. Among the FDA
      approved therapeutic modalities for FPHL are topical minoxidil and more recently
      low-level light therapy (LLLT). AIM OF WORK: Assess the efficacy and safety of
      LLLT in comparison to topical minoxidil 5% and to a combination of both therapies
      in the treatment of FPHL. PATIENTS AND METHODS: This study included 45 female
      patients with proven FPHL. They were randomly divided into three equal groups,
      where group (i) patients were instructed to apply topical minoxidil 5% twice
      daily, group (ii) patients received LLLT using the helmet iGrow(r) device for 25
      minutes 3 days weekly, and group (iii) patients received a combination of both
      topical minoxidil 5% twice daily and LLLT for 25 minutes 3 days weekly for 4
      months (study duration). Evaluation was done according to clinical, dermoscopic
      (folliscopic), and ultrasound bio-microscopic (UBM) parameters. Patient
      satisfaction and side effects were reported. RESULTS: The efficacy and safety of
      both topical minoxidil and LLLT were highlighted with comparable results in all
      parameters. The combination group (iii) occupied the top position regarding
      Ludwig classification and patient satisfaction. UBM and dermoscopic findings
      showed significant increase in the number of regrowing hair follicles at 4 months
      in all groups, whereas only UBM showed such significant increase at 2 months in
      the combination group (iii). A non-significant increase in the hair diameter was
      also documented in the three groups. CONCLUSION: LLLT is an effective and safe
      tool with comparable results to minoxidil 5% in the treatment of FPHL. Owing to
      the significantly better results of combination therapy, its usage is recommended
      to hasten hair regrowth. Lasers Surg. Med. 49:835-843, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28489274
TI  - Ultrasound Imaging Based on Molecular Targeting for Quantitative Evaluation of
      Hepatic Ischemia-Reperfusion Injury.
AB  - The aim of the present study was to quantitatively diagnose and monitor the
      therapy response of hepatic ischemia-reperfusion injury (IRI) with the use of
      targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated,
      and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs
      was observed. To establish a quantitative method based on targeted US imaging,
      contrast-enhanced US was applied for IRI rats. After andrographolide treatment,
      the IRI rats were subjected to the quantitative targeted US imaging for a
      therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed.
      According to the quantitative targeted US imaging, the ICAM-1 normalized
      intensity difference (NID) in the IRI rats (38.74 +/- 15.08%) was significantly
      higher than that in the control rats (10.08 +/- 2.52%, p = 0.048). Further,
      different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by
      the use of the NID (37.14 +/- 2.14%, 22.34 +/- 1.08%, p = 0.002). Analysis of
      mRNA expression demonstrated the accuracy of analyzing the NID by using
      quantitative targeted US imaging (R2  = 0.7434, p < 0.001). Andrographolide
      treatment resulted in an obviously weakened NID of ICAM-1 (17.7 +/- 4.8% vs 34.2
      +/- 6.6%, p < 0.001). The study showed the potential of the quantitative targeted
      US imaging method for the diagnosis and therapeutic monitoring of IRI.

PMID- 28489275
TI  - Recent drug therapies for corneal neovascularization.
AB  - Corneal neovascularization (CNV) is a common pathological change in ocular
      surface diseases. It is not only the factor that affects vision but also the main
      cause for corneal graft failure. Based on the mechanism of CNV, many achievements
      have been developed to suppress the formation of CNV. There are certain novel
      drugs such as aflibercept, gold nanoparticles, and netrins which provide us with
      new clues to treat CNV. However, we still need to develop more effective
      therapeutic drugs. It is of great significance to develop new effective drugs to
      suppress the occurrence of CNV. In this paper, recent drug therapies for CNV are
      reviewed. The electronic database (PubMed) is searched for relative basic
      research and randomized clinical trials that are published recently.

PMID- 28489276
TI  - Design, synthesis, and preliminary bioactivity evaluation of N-benzylpyrimidin-2
      amine derivatives as novel histone deacetylase inhibitor.
AB  - Histone deacetylase (HDAC) inhibitors have been identified for the treatment of
      cancer. Lately, we designed and synthesized a series of substituted N
      benzylpyrimidin-2-amine derivatives as potent HDAC inhibitors. In vitro HDAC
      inhibitory activities and antiproliferative activities of target compounds were
      investigated. Some target compounds showed potent HDAC inhibitory activities and
      possessed obvious antiproliferative activity against tumor cells. Target
      compounds 6a, 6d, 8a, 8c, and 8f not only exhibited almost equally enzymatic
      inhibitory activity with SAHA, but showed better antiproliferative activities.

PMID- 28489277
TI  - Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for
      Restoring Durable Insulin Independence.
AB  - Islet transplantation offers a minimally invasive approach for beta cell
      replacement in diabetic patients with hypoglycemic unawareness. Attempts at
      insulin independence may require multiple islet reinfusions from distinct donors,
      increasing the risk of allogeneic sensitization. Currently, solid organ pancreas
      transplant is the only remaining surgical option following failed islet
      transplantation in the United States; however, the immunologic impact of repeated
      exposure to donor antigens on subsequent pancreas transplantation is unclear. We
      describe a case series of seven patients undergoing solid organ pancreas
      transplant following islet graft failure with long-term follow-up of pancreatic
      graft survival and renal function. Despite highly variable panel reactive
      antibody levels prior to pancreas transplant (mean 27 +/- 35%), all seven
      patients achieved stable and durable insulin independence with a mean follow-up
      of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet,
      prepancreas levels (mean 8.1 +/- 1.5%) to postpancreas levels (mean 5.3 +/- 0.1%;
      p = 0.0022). Three patients experienced acute rejection episodes that were
      successfully managed with thymoglobulin and methylprednisolone, and none of these
      preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney
      disease postoperatively. These results support pancreas-after-islet
      transplantation with aggressive immunosuppression and protocol biopsies as a
      viable strategy to restore insulin independence after islet graft failure.

PMID- 28489278
TI  - Growth of indoor fungi on gypsum.
AB  - AIMS: To have a better understanding of fungal growth on gypsum building
      materials to prevent indoor fungal growth. METHODS AND RESULTS: Gypsum is
      acquired by mining or as a by-product of flue-gas desulphurization or treatment
      of phosphate ore for the production of fertilizer. Natural gypsum, flue-gas
      gypsum and phosphogypsum therefore have different mineral compositions. Here,
      growth of fungi on these types of gypsum was assessed. Conidia of the indoor
      fungi Aspergillus niger, Cladosporium halotolerans and Penicillium rubens were
      inoculated and observed using microscopic techniques including low-temperature
      scanning electron microscopy. Elemental analysis of gypsum was done using
      inductively coupled plasma atomic emission spectroscopy and segmented flow
      analysis. Moisture content of the gypsum was determined using a dynamic vapour
      sorption apparatus. Aspergillus niger, C. halotolerans and P. rubens hardly
      germinated on natural gypsum and flue-gas gypsum. The latter two fungi did show
      germination, outgrowth, and conidiation on phosphogypsum, while A. niger hardly
      germinated on this substrate. Other experiments show that C. halotolerans and P.
      rubens can develop in pure water, but A. niger does not. CONCLUSIONS: The
      observations show that the lack of germination of three indoor fungi is explained
      by the low amount of phosphor in natural, flue-gas and laboratory-grade gypsum.
      Additionally, C. halotolerans and P. rubens can develop in pure water, while
      conidia of A. niger do not show any germination, which is explained by the need
      for organic molecules of this species to induce germination. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Indoor fungal growth is a potential threat to human health
      and causes damage to building materials. This study possibly helps in the
      application of the right type of gypsum in buildings.

PMID- 28489280
TI  - Synthesis and evaluation of cytotoxic activities of artemisinin derivatives.
AB  - Artemisinin is a naturally occurring antimalarial agent which has shown potent
      anticancer activity. In this work, new artemisinin derivatives with the
      piperazine group were synthesized. The cytotoxic activities of derivatives 5a-5d
      were evaluated by MTT assay against ten cell lines. The results showed that 5a-5d
      were more effective in inhibiting cancer cell growth than artemisinin. 5d was the
      most active against HepG2 and PLC-PRF-5 cells and presented no cytotoxicity on L
      02 cells. Hoechst 33342 staining and flow cytometry experiment revealed that 5d
      could induce HepG2 and PLC-PRF-5 cell apoptosis. Flow cytometry analysis showed
      that 5d induced the loss of mitochondrial membrane potential (MMP) and increased
      the levels of intracellular free calcium and reactive oxygen species. 5d also
      induced cell cycle arrest in G2/M phase in HepG2 cells. According to the results
      of Western blotting and caspase-3 kit, 5d could significantly increase the
      content of p53, bax, Apaf-1, and caspase-3 and decrease the protein level of bcl
      2, pro-caspase-9, and pro-caspase-3 in HepG2 cells. These findings indicate that
      5d activates the mitochondria-mediated apoptotic pathway in HepG2 cells and may
      merit further investigation as a potential therapeutic agent for hepatocellular
      carcinoma.

PMID- 28489279
TI  - Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1
      analogues for prevention or delay of type 2 diabetes mellitus and its associated
      complications in people at increased risk for the development of type 2 diabetes
      mellitus.
AB  - BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus
      (T2DM) could develop into a substantial health problem worldwide. Whether
      dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1
      analogues are able to prevent or delay T2DM and its associated complications in
      people at risk for the development of T2DM is unknown. OBJECTIVES: To assess the
      effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of
      T2DM and its associated complications in people with impaired glucose tolerance,
      impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c
      (HbA1c) or any combination of these. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials; MEDLINE; PubMed; Embase;
      ClinicalTrials.gov; the World Health Organization (WHO) International Clinical
      Trials Registry Platform; and the reference lists of systematic reviews, articles
      and health technology assessment reports. We asked investigators of the included
      trials for information about additional trials. The date of the last search of
      all databases was January 2017. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) with a duration of 12 weeks or more comparing DPP-4
      inhibitors and GLP-1 analogues with any pharmacological glucose-lowering
      intervention, behaviour-changing intervention, placebo or no intervention in
      people with impaired fasting glucose, impaired glucose tolerance, moderately
      elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS: Two review
      authors read all abstracts and full-text articles and records, assessed quality
      and extracted outcome data independently. One review author extracted data which
      were checked by a second review author. We resolved discrepancies by consensus or
      the involvement of a third review author. For meta-analyses, we planned to use a
      random-effects model with investigation of risk ratios (RRs) for dichotomous
      outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence
      intervals (CIs) for effect estimates. We assessed the overall quality of the
      evidence using the GRADE instrument. MAIN RESULTS: We included seven completed
      RCTs; about 98 participants were randomised to a DPP-4 inhibitor as monotherapy
      and 1620 participants were randomised to a GLP-1 analogue as monotherapy. Two
      trials investigated a DPP-4 inhibitor and five trials investigated a GLP-1
      analogue. A total of 924 participants with data on allocation to control groups
      were randomised to a comparator group; 889 participants were randomised to
      placebo and 33 participants to metformin monotherapy. One RCT of liraglutide
      contributed 85% of all participants. The duration of the intervention varied from
      12 weeks to 160 weeks. We judged none of the included trials at low risk of bias
      for all 'Risk of bias' domains and did not perform meta-analyses because there
      were not enough trials.One trial comparing the DPP-4 inhibitor vildagliptin with
      placebo reported no deaths (very low-quality evidence). The incidence of T2DM by
      means of WHO diagnostic criteria in this trial was 3/90 participants randomised
      to vildagliptin versus 1/89 participants randomised to placebo (very low-quality
      evidence). Also, 1/90 participants on vildagliptin versus 2/89 participants on
      placebo experienced a serious adverse event (very low-quality evidence). One out
      of 90 participants experienced congestive heart failure in the vildagliptin group
      versus none in the placebo group (very low-quality evidence). There were no data
      on non-fatal myocardial infarction, stroke, health-related quality of life or
      socioeconomic effects reported.All-cause and cardiovascular mortality following
      treatment with GLP-1 analogues were rarely reported; one trial of exenatide
      reported that no participant died. Another trial of liraglutide 3.0 mg showed
      that 2/1501 in the liraglutide group versus 2/747 in the placebo group died after
      160 weeks of treatment (very low-quality evidence).The incidence of T2DM
      following treatment with liraglutide 3.0 mg compared to placebo after 160 weeks
      was 26/1472 (1.8%) participants randomised to liraglutide versus 46/738 (6.2%)
      participants randomised to placebo (very low-quality evidence). The trial
      established the risk for (diagnosis of) T2DM as HbA1c 5.7% to 6.4% (6.5% or
      greater), fasting plasma glucose 5.6 mmol/L or greater to 6.9 mmol/L or less (7.0
      mmol/L or greater) or two-hour post-load plasma glucose 7.8 mmol/L or greater to
      11.0 mmol/L (11.1 mmol/L). Altogether, 70/1472 (66%) participants regressed from
      intermediate hyperglycaemia to normoglycaemia compared with 268/738 (36%)
      participants in the placebo group. The incidence of T2DM after the 12-week off
      treatment extension period (i.e. after 172 weeks) showed that five additional
      participants were diagnosed T2DM in the liraglutide group, compared with one
      participant in the placebo group. After 12-week treatment cessation, 740/1472
      (50%) participants in the liraglutide group compared with 263/738 (36%)
      participants in the placebo group had normoglycaemia.One trial used exenatide and
      2/17 participants randomised to exenatide versus 1/16 participants randomised to
      placebo developed T2DM (very low-quality evidence). This trial did not provide a
      definition of T2DM. One trial reported serious adverse events in 230/1524 (15.1%)
      participants in the liraglutide 3.0 mg arm versus 96/755 (12.7%) participants in
      the placebo arm (very low quality evidence). There were no serious adverse events
      in the trial using exenatide. Non-fatal myocardial infarction was reported in
      1/1524 participants in the liraglutide arm and in 0/55 participants in the
      placebo arm at 172 weeks (very low-quality evidence). One trial reported
      congestive heart failure in 1/1524 participants in the liraglutide arm and in
      1/755 participants in the placebo arm (very low-quality evidence). Participants
      receiving liraglutide compared with placebo had a small mean improvement in the
      physical component of the 36-item Short Form scale showing a difference of 0.87
      points (95% CI 0.17 to 1.58; P = 0.02; 1 trial; 1791 participants; very low
      quality evidence). No trial evaluating GLP-1-analogues reported data on stroke,
      microvascular complications or socioeconomic effects. AUTHORS' CONCLUSIONS: There
      is no firm evidence that DPP-4 inhibitors or GLP-1 analogues compared mainly with
      placebo substantially influence the risk of T2DM and especially its associated
      complications in people at increased risk for the development of T2DM. Most
      trials did not investigate patient-important outcomes.

PMID- 28489282
TI  - Collaborative writing applications in healthcare: effects on professional
      practice and healthcare outcomes.
AB  - BACKGROUND: Collaborative writing applications (CWAs), such as wikis and Google
      Documents, hold the potential to improve the use of evidence in both public
      health and healthcare. Although a growing body of literature indicates that CWAs
      could have positive effects on healthcare, such as improved collaboration,
      behavioural change, learning, knowledge management, and adaptation of knowledge
      to local context, this has never been assessed systematically. Moreover, several
      questions regarding safety, reliability, and legal aspects exist. OBJECTIVES: The
      objectives of this review were to (1) assess the effects of the use of CWAs on
      process (including the behaviour of healthcare professionals) and patient
      outcomes, (2) critically appraise and summarise current evidence on the use of
      resources, costs, and cost-effectiveness associated with CWAs to improve
      professional practices and patient outcomes, and (3) explore the effects of
      different CWA features (e.g. open versus closed) and different implementation
      factors (e.g. the presence of a moderator) on process and patient outcomes.
      SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and 11 other electronic
      databases. We searched the grey literature, two trial registries, CWA websites,
      individual journals, and conference proceedings. We also contacted authors and
      experts in the field. We did not apply date or language limits. We searched for
      published literature to August 2016, and grey literature to September 2015.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs), non
      randomised controlled trials (NRCTs), controlled before-and-after (CBA) studies,
      interrupted time series (ITS) studies, and repeated measures studies (RMS), in
      which CWAs were used as an intervention to improve the process of care, patient
      outcomes, or healthcare costs. DATA COLLECTION AND ANALYSIS: Teams of two review
      authors independently assessed the eligibility of studies. Disagreements were
      resolved by discussion, and when consensus was not reached, a third review author
      was consulted. MAIN RESULTS: We screened 11,993 studies identified from the
      electronic database searches and 346 studies from grey literature sources. We
      analysed the full text of 99 studies. None of the studies met the eligibility
      criteria; two potentially relevant studies are ongoing. AUTHORS' CONCLUSIONS:
      While there is a high number of published studies about CWAs, indicating that
      this is an active field of research, additional studies using rigorous
      experimental designs are needed to assess their impact and cost-effectiveness on
      process and patient outcomes.

PMID- 28489281
TI  - Unveiling microbial interactions in stratified mat communities from a warm saline
      shallow pond.
AB  - Modern phototrophic microbial mats are complex communities often used as analogs
      of major Precambrian ecosystems. Characterizing biotic, notably metabolic,
      interactions among different microbial mat members is essential to gain insights
      into the ecology and biogeochemistry of these systems. We applied 16S/18S rRNA
      metabarcoding approaches to characterize the structure of archaea, bacteria and
      protist communities from microbial mats collected along strong physicochemical
      (oxygen, salinity, temperature, depth) gradients in a shallow pond at the salar
      de Llamara (Chile). All mats were highly diverse, including members of virtually
      all known high-rank eukaryotic and prokaryotic taxa but also many novel lineages.
      Bacterial candidate divisions accounted for almost 50% of sequences in deeper
      mats, while Archaea represented up to 40% of sequences in some mat layers.
      Molecular phylogenetic analyses revealed six novel deeply divergent archaeal
      groups, along abundant and diverse Pacearchaeota and Woesearchaeota. Multivariate
      statistical analyses showed that local environmental conditions strongly
      influenced community composition. Co-occurrence network structure was markedly
      different between surface mats located in the oxygenated zone and mats located in
      transition and anoxic water layers. We identified potential biotic interactions
      between various high- and low-rank taxa. Notably, a strong positive correlation
      was observed between Lokiarchaeota and the poorly known candidate bacterial
      division TA06.

PMID- 28489283
TI  - Inflammatory responses, matrix remodeling, and re-epithelialization after
      fractional CO2 laser treatment of scars.
AB  - BACKGROUND AND OBJECTIVE: Fractional CO2 laser therapy has been used to improve
      scar pliability and appearance; however, a variety of treatment protocols have
      been utilized with varied outcomes. Understanding the relationship between laser
      power and extent of initial tissue ablation and time frame for remodeling could
      help determine an optimum power and frequency for laser treatment. The
      characteristics of initial injury caused by fractional CO2 laser treatment, the
      rates of dermal remodeling and re-epithelialization, and the extent of
      inflammation as a function of laser stacking were assessed in this study in a
      porcine scar model. MATERIALS AND METHODS: Full-thickness burn wounds were
      created on female Red Duroc pigs followed by immediate excision of the eschar and
      split-thickness autografting. Three months after injury, the resultant scars were
      treated with a fractional CO2 laser with 70 mJ of energy delivered as either a
      single pulse or stacked for three consecutive pulses. Immediately prior to laser
      treatment and at 1, 24, 96, and 168 hours post-laser treatment, transepidermal
      water loss (TEWL), erythema, and microscopic characteristics of laser injury were
      measured. In addition, markers for inflammatory cytokines, extracellular matrix
      proteins, and re-epithelialization were quantified at all time points using qRT
      PCR. RESULTS: Both treatments produced erythema in the scar that peaked 24 hours
      after treatment then decreased to basal levels by 168 hours. TEWL increased after
      laser treatment and returned to normal levels between 24 and 96 hours later.
      Stacking of the pulses did not significantly increase the depth of ablated wells
      or extend the presence of erythema. Interleukin 6 and monocyte chemoattractant
      protein-1 were found to increase significantly 1 hour after treatment but
      returned to baseline by 24 hours post laser. In contrast, expression of
      transforming growth factor beta1 and transforming growth factor beta3 increased
      slowly after treatment with a more modest increase than interleukin 6 and
      monocyte chemoattractant protein-1. CONCLUSIONS: In the current study, the
      properties of the ablative zones were not directly proportional to the total
      amount of energy applied to the porcine scars with the use of triple stacking,
      resulting in only minor increases to microthermal zone (MTZ) depth and width
      versus a single pulse. Re-epithelialization and re-establishment of epidermal
      barrier function were observed in laser treated scars by 48 hours post therapy.
      Finally, many of the inflammatory genes up-regulated by the laser ablation
      returned to baseline within 1 week. As a whole, these results suggest that
      microthermal zones created by FXCO2 treatment re-epithelialize rapidly with the
      inflammatory response to the laser induced injury largely resolved within 1 week
      post treatment. Further study is needed to understand the relationship between
      laser stacking and MTZ properties in human scars in order to evaluate the
      clinical applicability of the stacking technique. Lasers Surg. Med. 49:675-685,
      2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28489284
TI  - Mapping genotype-phenotype associations of nsSNPs in coiled-coil oligomerization
      domains of the human proteome.
AB  - We assessed the impact of disease mutations (DMs) versus polymorphisms (PYs) in
      coiled-coil (CC) domains in UniProt by modeling the structural and functional
      impact of variants in silico with the CC prediction program Multicoil. The
      structural impact of variants was evaluated with respect to three main metrics:
      the oligomerization score-to determine whether the variant is stabilizing or
      destabilizing-the oligomerization state, and the register-specific score. The
      functional impact was queried indirectly in several ways. First, we examined
      marginally stable CCs that were either stabilized or destabilized by the variant.
      Second, we looked for variants that altered the register of the wild-type CC near
      wild-type irregularities of likely functional importance, such as skips and
      stammers. Third, we searched for variants that altered the oligomerization state
      of the CC. DMs tended to be more destabilizing than PYs; but interestingly, PYs
      were more frequently associated with predicted changes in the oligomerization
      state. The functional impact was also queried by testing the association of CC
      variants with multiple phenotypes, that is, pleiotropy. Mutations in CC regions
      of proteins cause 155 different phenotypes and are more frequently associated
      with pleiotropy than proteins in general. Importantly, the CC region itself often
      encodes the pleiotropy.

PMID- 28489285
TI  - SCAI appropriate use criteria for peripheral arterial interventions: An update.

PMID- 28489287
TI  - Broken Chains and Reneging: A Review of 1748 Kidney Paired Donation Transplants.
AB  - Concerns regarding the potential for broken chains and "reneges" within kidney
      paired donation (KPD) and its effect on chain length have been raised previously.
      Although these concerns have been tested in simulation studies, real-world data
      have yet to be evaluated. The purpose of this study was to evaluate the actual
      rate and causes of broken chains within a large KPD program. All patients
      undergoing renal transplantation through the National Kidney Registry from 2008
      through May 2016 were included for analysis. Broken chains and loops were
      identified. A total of 344 chains and 78 loops were completed during the study
      period, yielding a total of 1748 transplants. Twenty broken chains and one broken
      loop were identified. The mean chain length (number of transplants) within broken
      chains was 4.8 compared with 4.6 of completed chains (p = 0.78). The most common
      causes of a broken chain were donor medical issues incurred while acting as a
      bridge donor (n = 8), donors electing not to proceed (n = 6), and kidneys being
      declined by the recipient surgeon (n = 4). All recipients involved in a broken
      chain subsequently received a transplant. Based on the results, broken chains are
      infrequent, are rarely due to lack of donor motivation, and have no significant
      impact on chain length.

PMID- 28489286
TI  - Sustained activation of ERK1/2 MAPK in Schwann cells causes corneal neurofibroma.
AB  - Recent studies have shown that constitutive activation of extracellular signal
      regulated kinases 1 and 2 (ERK1/2) in Schwann cells (SCs) increases myelin
      thickness in transgenic mice. In this secondary analysis, we report that these
      transgenic mice develop a postnatal corneal neurofibroma with the loss of corneal
      transparency by age six months. We show that expansion of non-myelinating SCs,
      under the control of activated ERK1/2, also drive myofibroblast differentiation
      that derives from both SC precursors and resident corneal keratocytes. Further,
      these mice also harbor activated mast cells in the central cornea, which
      contributes to pathological corneal neovascularization and fibrosis. This breach
      of corneal avascularity and immune status is associated with the growth of the
      tumor pannus, resulting in a corneal stroma that is nearly four times its normal
      size. In corneas with advanced disease, some axons became ectopically myelinated,
      and the disruption of Remak bundles is evident. To determine whether
      myofibroblast differentiation was linked to vimentin, we examined the levels and
      phosphorylation status of this fibrotic biomarker. Concomitant with the early
      upregulation of vimentin, a serine 38-phosphorylated isoform of vimentin
      (pSer38vim) increased in SCs, which was attributed primarily to the soluble
      fraction of protein-not the cytoskeletal portion. However, the overexpressed
      pSer38vim became predominantly cytoskeletal with the growth of the corneal tumor.
      Our findings demonstrate an unrecognized function of ERK1/2 in the maintenance of
      corneal homeostasis, wherein its over-activation in SCs promotes corneal
      neurofibromas. This study is also the first report of a genetically engineered
      mouse that spontaneously develops a corneal tumor.

PMID- 28489288
TI  - Enhanced cognitive behavioral therapy for eating disorders adapted for a group
      setting.
AB  - OBJECTIVE: This randomized control trial is an evaluation of the effectiveness of
      enhanced cognitive behavioral treatment (CBT-E) for eating disorders adapted for
      a group setting. The study aimed to examine the effects of group CBT-E on eating
      disorder psychopathology and additional maintaining pathology. METHOD: A
      transdiagnostic sample of individuals with eating disorders with a BMI >= 18
      kg/m2 (N = 40) were randomized to an immediate-start or delayed-start condition
      so as to compare therapeutic effects of group CBT-E with a waitlist control.
      Global Eating Disorder Examination Questionnaire (EDE-Q) scores, BMI, and
      measures of Clinical Perfectionism, Self-Esteem, Interpersonal Difficulties, and
      Mood Intolerance were measured across the 8-week control period, throughout the
      group treatment and at 3-months post-treatment. RESULTS: Over 70% of those who
      entered the trial completed treatment. The first eight weeks of group CBT-E were
      more effective at reducing Global EDE-Q scores than no treatment (waitlist
      control). By post-treatment, good outcome (a Global EDE-Q within 1 SD of
      Australian community norms plus BMI >= 18.5) was achieved by 67.9% of treatment
      completers and 66.7% of the total sample. Symptom abstinence within the previous
      month was reported by 14.3% of treatment completers and 10.3% of the total
      sample. Significant reductions in Clinical Perfectionism, Self-Esteem,
      Interpersonal Difficulties, and Mood Intolerance were also observed. DISCUSSION:
      This study demonstrated that a group version of CBT-E can be effective at
      reducing eating disorder psychopathology in a transdiagnostic sample of
      individuals with eating disorders. Group CBT-E could provide a means of
      increasing availability of evidence-based treatment for eating disorders.

PMID- 28489289
TI  - Introducing high-flow nasal cannula to the neonatal transport environment.

PMID- 28489290
TI  - Obesity: a chronic relapsing progressive disease process. A position statement of
      the World Obesity Federation.
AB  - This paper considers the argument for obesity as a chronic relapsing disease
      process. Obesity is viewed from an epidemiological model, with an agent affecting
      the host and producing disease. Food is the primary agent, particularly foods
      that are high in energy density such as fat, or in sugar-sweetened beverages. An
      abundance of food, low physical activity and several other environmental factors
      interact with the genetic susceptibility of the host to produce positive energy
      balance. The majority of this excess energy is stored as fat in enlarged, and
      often more numerous fat cells, but some lipid may infiltrate other organs such as
      the liver (ectopic fat). The enlarged fat cells and ectopic fat produce and
      secrete a variety of metabolic, hormonal and inflammatory products that produce
      damage in organs such as the arteries, heart, liver, muscle and pancreas. The
      magnitude of the obesity and its adverse effects in individuals may relate to the
      virulence or toxicity of the environment and its interaction with the host. Thus,
      obesity fits the epidemiological model of a disease process except that the toxic
      or pathological agent is food rather than a microbe. Reversing obesity will
      prevent most of its detrimental effects.

PMID- 28489291
TI  - Long-term outcomes of early compared to late onset choledochocholedochal
      anastomotic strictures after orthotopic liver transplantation.
AB  - BACKGROUND: Endoscopic treatment of anastomotic biliary stricture (ABS) after
      liver transplantation (LT) has been proven to be effective and safe, but long
      term outcomes of early compared to late onset ABS have not been studied. The aim
      of this study is to compare the long-term outcome of early ABS to late ABS.
      METHODS: Of the 806 adult LT recipients (04/2006-12/2012), 93 patients met the
      criteria for inclusion, and were grouped into non-ABS (no stenosis on ERCP,
      n=41), early ABS (stenosis <90 days after LT, 18 [19.3%]), and late ABS (stenosis
      >=90 days after LT, 34 [36.5%]). A propensity matched control group for the ABS
      group (n=42) was obtained matched for outcome variables for age, gender, and
      calculated MELD score at listing. RESULTS: Mean number of ERCPs (2.33+/-1.3 vs
      2.56+/-1.5, P=.69) were comparable between the groups; however, significantly
      better long-term resolution of the stricture was noted in the early ABS group
      (94.44% vs 67.65%, P=.04). Kaplan-Meier analysis revealed worst survival in the
      early ABS group compared to the non-ABS, late ABS, and control groups (P=.0001).
      CONCLUSION: LT recipients with early ABS have inferior graft survival despite
      better response to endoscopic intervention.

PMID- 28489292
TI  - Dual Stimuli-Responsive Nanoparticles for Controlled Release of Anticancer and
      Anti-inflammatory Drugs Combination.
AB  - Dual stimuli-responsive nanoparticles capable of fine-tuning drug release to
      augment therapeutic efficacy have become a promising tool for anticancer drug
      delivery. However, the rational design of these "smart" nanoparticles for a
      selective delivery and controlled release of multidrug combinations in cancer
      cells to achieve synergistic effects remain challenging. Here we report the
      pH/redox dual responsive nanoparticle FA-DOX-Ind-NP (FA=folic acid,
      DOX=doxorubicin, Ind=indomethacin, NP=nanoparticle) based on the novel tumor
      targeting and biodegradable poly(beta-amino ester) polymer, and demonstrate its
      high ability to enter into cancer cells and release a combination of the
      anticancer drug doxorubicin and the non-steroidal anti-inflammatory drug
      indomethacin to achieve synergistic chemo-anti-inflammatory effects and overcome
      multidrug resistance. This study highlights the great potential of tumor
      targeting and dual stimuli-responsive nanoparticles for an efficient delivery of
      multidrug combination to improve the cancer therapeutic efficacy.

PMID- 28489294
TI  - A Transparent, Highly Stretchable, Autonomous Self-Healing Poly(dimethyl
      siloxane) Elastomer.
AB  - An innovative self-healing polydimethylsiloxane (PDMS) elastomer, namely, PDMS
      TFB, is reported by incorporating the reversibly dynamic imine bond as the self
      healing points into the PDMS networks. The PDMS-TFB elastomer features good
      optical transmittance (80%) in full visible light region, high stretchability
      (~700%), and excellent autonomous self-healing ability at room temperature.
      Surprisingly, the self-healing behavior can take place in water and even at a
      temperature as low as -20  degrees C in air, showing a promising outlook for
      broader applications. As a proof-of-concept, this study demonstrates the use of
      the PDMS-TFB elastomer for preparing anticorrosion coating and adhesive layer,
      and also the use of such an elastomer to be the platform for fabricating the
      flexible interconnector and chemical sensor. Remarkably, no significant
      difference is observed between the pristine and healed samples. Taking full
      advantage of these unique properties, it is anticipated that such a PDMS-TFB
      elastomer shows wide applications in the fields of materials science,
      electronics, biology, optics, etc.

PMID- 28489295
TI  - A pH-Responsive DNAsome from the Self-Assembly of DNA-Phenyleneethynylene Hybrid
      Amphiphile.
AB  - A pH-responsive DNAsome derived from the amphiphilicity-driven self-assembly of
      DNA amphiphile containing C-rich DNA sequence is reported. The acidification of
      DNAsome induces a structural change of C-rich DNA from random coil to an i-motif
      structure that triggers the disassembly of DNAsome and its subsequent
      morphological transformation into an open entangled network. The encapsulation of
      a hydrophobic guest into the membrane of DNAsome and its pH-triggered release
      upon acidification of DNAsome is also demonstrated.

PMID- 28489293
TI  - The role of family history of depression and the menopausal transition in the
      development of major depression in midlife women: Study of women's health across
      the nation mental health study (SWAN MHS).
AB  - BACKGROUND: This study evaluated whether family history of depression predicts
      major depression in midlife women above and beyond static risk factors (such as
      personal history of depression prior to midlife) and risks that may change
      dynamically across midlife (such as menopausal, psychosocial, and health
      profiles). METHODS: Participants were 303 African American and Caucasian women
      (42-52 years at baseline) recruited into the Study of Women's Health across the
      Nation (SWAN) Mental Health Study (MHS) in Pittsburgh. Major depression was
      assessed annually with Structured Clinical Interviews for DSM-IV. Family mental
      health history was collected at the ninth or tenth annual follow-up. Random
      effects logistic regression was used to assess the relationship between family
      history of depression and midlife depression, controlling for baseline
      sociodemographic characteristics and time-varying risk factors. RESULTS: Family
      history of depression was associated with midlife depression after adjusting for
      participant's history of major depression prior to midlife, trait anxiety and
      baseline age, and time-varying menopausal status, body mass index, very upsetting
      life events, and chronic difficulties (OR = 2.24, 95% CI = 1.17-4.29, P = .02).
      Higher odds of major depression were found when women were late perimenopausal or
      postmenopausal relative to when they were premenopausal or early perimenopausal
      (OR = 3.01, 95% CI = 1.76-5.15, P < .0001). However, menopausal status was only
      associated with major depression among women without a family history.
      CONCLUSIONS: Family history of depression predicts major depression in midlife
      women independent of the menopausal transition and other time-varying covariates.
      Notably, the menopausal transition was associated with increased risk only among
      women without a family history of depression.

PMID- 28489296
TI  - Rapid actions of oestrogens and their receptors on memory acquisition and
      consolidation in females.
AB  - Increased attention has been paid in recent years to the ways in which oestrogens
      and oestrogen receptors rapidly affect learning and memory. These rapid effects
      occur within a timeframe that is too narrow for the classical genomic mode of
      action of oestrogen, thus suggesting nonclassical effects as underlying
      mechanisms. The present review examines recent developments in the study of the
      rapid effects of 17beta-oestradiol and oestrogen receptor (ER) agonists on
      learning and memory tasks in female rodents, including social recognition, object
      recognition, object placement (spatial memory) and social learning. By comparing
      studies utilising systemic or intracranial treatments, as well as pre- and post
      acquisition administration of oestradiol or ER agonists, the respective
      contributions of individual ERs within specific brain regions to various forms of
      learning and memory can be determined. The first part of this review explores the
      effects of systemic administration of 17beta-oestradiol and ER agonists on memory
      when administered either pre- or post-acquisition. The second part not only
      focuses on the effects of pre- and post-acquisition infusions of 17beta
      oestradiol or ER agonists into the dorsal hippocampus on memory, but also
      discusses the contributions of other brain regions, including the medial
      amygdala, medial prefrontal cortex and paraventricular nucleus of the
      hypothalamus. The cellular mechanisms mediating the rapid effects of 17beta
      oestradiol on memory, including activation of intracellular signalling cascades
      and epigenetic processes, are discussed. Finally, the review concludes by
      comparing pre- and post-acquisition findings and effects of 17beta-oestradiol and
      ER agonists in different brain regions.

PMID- 28489297
TI  - The effect of low-temperature laundering and detergents on the survival of
      Escherichia coli and Staphylococcus aureus on textiles used in healthcare
      uniforms.
AB  - AIMS: To determine the survival of Escherichia coli and Staphylococcus aureus on
      cotton and polyester and the effectiveness of low-temperature laundering and
      detergents on the removal of micro-organism from healthcare laundry. METHODS AND
      RESULTS: Survival of E. coli and S. aureus on polyester or cotton was assessed
      over 3 weeks and the efficacy of a domestic wash (40 and 60 degrees C) and a
      range of detergents was also determined. Both bacteria were able to survive on
      cotton (5 log(10) ) and polyester (0.28 log(10) ) for up to 3 weeks. Laundering
      at 40 degrees C resulted in a 3.5 log(10) removal of the initial 7.7 log(10)
      inoculum and some cross-contamination to sterile fabrics (3 log(10) ). Increasing
      the temperature to 60 degrees C resulted in the complete removal of the initial
      inoculum. CONCLUSIONS: This study shows that most of the micro-organisms are
      removed at 40 degrees C, however, those cells still remaining may have the
      potential for further contamination to the clinical environment and patients.
      SIGNIFICANCE AND IMPACT OF THE STUDY: National Health Service (NHS) nurses are
      required to domestically launder their uniforms at 60 degrees C to ensure safe
      removal of micro-organisms, 33% of NHS staff questioned said they launder their
      uniforms at 40 degrees C, which could potentially result in transmission of
      hospital-acquired infections.

PMID- 28489299
TI  - GP-patient communication about possible cancer in primary care: Re-evaluating GP
      as gatekeeper.
AB  - As possibilities for the early detection of indolent cancers, and precursors to
      cancer, multiply, GPs will increasingly be involved in discussions with patients
      about risks and benefits of early diagnosis and treatment. Over time,
      improvements in evidence may decrease uncertainty about outcomes for patients and
      clinicians. However, where survival benefits are small, or uncertain, or risks
      are unacceptable to patients, grounds for preference-sensitive decision-making
      will remain. How risks and benefits of early detection, and the significance of
      indolent or low risk cancers, are communicated, will be key, if overtreatment and
      overdiagnosis are to be avoided.

PMID- 28489298
TI  - A randomized, double-blind, placebo-controlled clinical trial evaluating the role
      of systemic antihistamine therapy for the reduction of adverse effects associated
      with topical 5-aminolevulinic acid photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVE: Following photodynamic therapy with 5-aminolevulinic
      acid (ALA-PDT), patients experience inflammation that may be partially
      attributable to H1 histamine receptor activation. The objective of this study was
      to evaluate the impact of antihistamines upon adverse effects following ALA-PDT.
      STUDY DESIGN/MATERIALS AND METHODS: This was a randomized, placebo-controlled
      clinical trial conducted at a single study site. Twenty subjects with facial
      actinic keratoses were randomized to ALA-PDT plus cetirizine 10 mg (n = 10)
      versus placebo daily (n = 10) from 3 days pre-treatment to 3 days post-treatment
      for a total of 7 days. Signs of inflammation including erythema, edema, crusting,
      exudation, vesiculation, and erosion were evaluated on post-treatment days 1, 2,
      3, 7, 30, 90, and 180. Actinic keratosis counts, investigator-rated Global
      Assessment Improvement Score (GAIS), healing, tolerability, and subject
      satisfaction were also assessed. RESULTS: Erythema, edema, crusting, exudation,
      vesiculation, and erosion were not different between treatment groups. Actinic
      keratoses were significantly reduced by day 30 in both the antihistamine and
      placebo groups (P = 0.01 and 0.0009, respectively), with results sustained to day
      60 in the antihistamine group and day 180 for the placebo group. However, counts
      were not different between groups at any time point. Investigator-rated GAIS,
      subject satisfaction, healing, and tolerability were similar between treatment
      groups. CONCLUSION: This study suggests that while H1 antihistamines do not
      impair the efficacy of ALA-PDT, they also do not relieve post-treatment
      inflammation and discomfort. Lasers Surg. Med. 49:738-742, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28489300
TI  - Predictors of PTSD 40 years after combat: Findings from the National Vietnam
      Veterans longitudinal study.
AB  - BACKGROUND: Few studies have longitudinally examined predictors of posttraumatic
      stress disorder (PTSD) in a nationally representative sample of US veterans. We
      examined predictors of warzone-related PTSD over a 25-year span using data from
      the National Vietnam Veterans Longitudinal Study (NVVLS). METHODS: The NVVLS is a
      follow-up study of Vietnam theater veterans (N = 699) previously assessed in the
      National Vietnam Veterans Readjustment Study (NVVRS), a large national
      probability study conducted in the late 1980s. We examined the ability of 22
      premilitary, warzone, and postmilitary variables to predict current warzone
      related PTSD symptom severity and PTSD symptom change in male theater veterans
      participating in the NVVLS. Data included a self-report Health Questionnaire
      survey and a computer-assisted telephone Health Interview Survey. Primary
      outcomes were self-reported PTSD symptoms assessed by the PTSD Checklist for DSM
      5 (PCL 5) and Mississippi PTSD Scale (M-PTSD). RESULTS: Predictors of current
      PTSD symptoms most robust in hierarchical multivariable models were African
      American race, lower education level, negative homecoming reception, lower
      current social support, and greater past-year stress. PTSD symptoms remained
      largely stable over time, and symptom exacerbation was predicted by African
      American race, lower education level, younger age at entry into Vietnam, greater
      combat exposure, lower current social support, and greater past-year stressors.
      CONCLUSIONS: Findings confirm the robustness of a select set of risk factors for
      warzone-related PTSD, establishing that these factors can predict PTSD symptom
      severity and symptom change up to 40 years postdeployment.

PMID- 28489301
TI  - Hyperelastic Tough Gels through Macrocross-Linking.
AB  - The wet and soft nature of hydrogels makes them useful as a mimic for biological
      tissues, and in uses such as actuators and drug delivery vehicles. For many
      applications the mechanical performance of the gel is critical, but gels are
      notoriously weak and prone to fracture. Free radical polymerization is a very
      powerful technique allowing for fine spatial and temporal control of
      polymerization, but also allows for the use of a wide range of monomers and
      mixtures. In this work, it is demonstrated that extremely tough and extensible
      hydrogels can be readily produced through simple radical polymerization of
      acrylamide or acrylic acid with a poly(ethylene oxide) macrocross-linker. These
      gels, with a water content of 85%, are extremely elastic with an extension much
      more than 15 000% at 9 MPa true stress. They can be compressed over 98% at a
      stress of 17 MPa. They are notch-insensitive, and the usual trouser tear test
      does not work because the tear simply does not propagate. This highly extensible
      nature seems to be related to very long chain lengths between cross-links and
      efficient incorporation of chains into the network.

PMID- 28489302
TI  - Characterization of a furan aldehyde-tolerant beta-xylosidase/alpha-arabinosidase
      obtained through a synthetic metagenomics approach.
AB  - AIMS: The aim of the study was to characterize 10 hemicellulolytic enzymes
      obtained from a wheat straw-degrading microbial consortium. METHODS AND RESULTS:
      Based on previous metagenomics analyses, 10 glycosyl hydrolases were selected,
      codon-optimized, synthetized, cloned and expressed in Escherichia coli. Nine of
      the overexpressed recombinant proteins accumulated in cellular inclusion bodies,
      whereas one, a 37.5-kDa protein encoded by gene xylM1989, was found in the
      soluble fractions. The resulting protein, denoted XylM1989, showed beta
      xylosidase and alpha-arabinosidase activities. It fell in the GH43 family and
      resembled a Sphingobacterium sp. protein. The XylM1989 showed optimum activity at
      20 degrees C and pH 8.0. Interestingly, it kept approximately 80% of its beta
      xylosidase activity in the presence of 0.5% (w/v) furfural and 0.1% (w/v) 5
      hydroxymethylfurfural. Additionally, the presence of Ca2+ , Mg2+ and Mn2+ ions
      increased the enzymatic activity and conferred complete tolerance to 500 mmol l-1
      of xylose. Protein XylM1989 is also able to release sugars from complex
      polysaccharides. CONCLUSION: We report the characterization of a novel
      bifunctional hemicellulolytic enzyme obtained through a targeted synthetic
      metagenomics approach. SIGNIFICANCE AND IMPACT OF THE STUDY: The properties of
      XylM1989 turn this protein into a promising enzyme that could be useful for the
      efficient saccharification of plant biomass.

PMID- 28489304
TI  - Infection of the fittest: devil facial tumour disease has greatest effect on
      individuals with highest reproductive output.
AB  - Emerging infectious diseases rarely affect all members of a population equally
      and determining how individuals' susceptibility to infection is related to other
      components of their fitness is critical to understanding disease impacts at a
      population level and for predicting evolutionary trajectories. We introduce a
      novel state-space model framework to investigate survival and fecundity of
      Tasmanian devils (Sarcophilus harrisii) affected by a transmissible cancer, devil
      facial tumour disease. We show that those devils that become host to tumours have
      otherwise greater fitness, with higher survival and fecundity rates prior to
      disease-induced death than non-host individuals that do not become infected,
      although high tumour loads lead to high mortality. Our finding that individuals
      with the greatest reproductive value are those most affected by the cancer
      demonstrates the need to quantify both survival and fecundity in context of
      disease progression for understanding the impact of disease on wildlife
      populations.

PMID- 28489303
TI  - N2 -to-NH3 Conversion by a triphos-Iron Catalyst and Enhanced Turnover under
      Photolysis.
AB  - Bridging iron hydrides are proposed to form at the active site of MoFe
      nitrogenase during catalytic dinitrogen reduction to ammonia and may be key in
      the binding and activation of N2 via reductive elimination of H2 . This
      possibility inspires the investigation of well-defined molecular iron hydrides as
      precursors for catalytic N2 -to-NH3 conversion. Herein, we describe the synthesis
      and characterization of new P2P'Ph Fe(N2 )(H)x systems that are active for
      catalytic N2 -to-NH3 conversion. Most interestingly, we show that the yields of
      ammonia can be significantly increased if the catalysis is performed in the
      presence of mercury lamp irradiation. Evidence is provided to suggest that photo
      elimination of H2 is one means by which the enhanced activity may arise.

PMID- 28489306
TI  - Pipecolic Acid Hydroxylases: A Monophyletic Clade among cis-Selective Bacterial
      Proline Hydroxylases that Discriminates l-Proline.
AB  - Proline hydroxylases are iron(II)/2-oxoglutarate-dependent enzymes that
      hydroxylate l-proline and derivatives, such as lpipecolic acid, which is the six
      membered-ring homologue of l-proline. It has been established that there is a
      distinct group of conserved bacterial enzymes that hydroxylate l-pipecolic acid
      and trans-3- and trans-4-methyl-l-proline, but virtually no l-proline. This
      allows the organism to produce hydroxyproline congeners without hydroxylation of
      the physiologically omnipresent l-proline. In vitro conversions showed that the
      substrate spectrum of the pipecolic acid hydroxylases GetF (from a Streptomyces
      sp.; producer of the tetrapeptide antibiotic GE81112) and PiFa (from Frankia
      alni) overlaps that of proline hydroxylases, except for the nonacceptance of l
      proline and smaller homologues. Distinct and conserved residues were determined
      for both types of enzymes. However, site-directed mutagenesis in GetF did not
      yield variants that accepted l-proline; this suggested a complex interaction of
      several residues around the active site, which resulted in delicate changes in
      substrate specificity. This is supported by substrate docking in a homology model
      of GetF, which revealed an altered orientation for l-proline relative to that of
      preferred substrates.

PMID- 28489305
TI  - Prolonged Survival Following Pig-to-Primate Liver Xenotransplantation Utilizing
      Exogenous Coagulation Factors and Costimulation Blockade.
AB  - Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in
      1968, survival has been limited. We evaluated a model utilizing alpha-1,3
      galactosyltransferase knockout donors, continuous posttransplant infusion of
      human prothrombin concentrate complex, and immunosuppression including anti
      thymocyte globulin, FK-506, methylprednisone, and costimulation blockade
      (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained
      well until postoperative day (POD) 25, when euthanasia was required because of
      cholestasis and plantar ulcers. Baboon 2 was euthanized following a seizure on
      POD 5, despite normal liver function tests (LFTs) and no apparent pathology.
      Baboon 3 demonstrated initial stable liver function but was euthanized on POD 8
      because of worsening LFTs. Pathology revealed C4d positivity, extensive
      hemorrhagic necrosis, and a focal cytomegalovirus inclusion. Baboon 4 was
      clinically well with stable LFTs until POD29, when euthanasia was again
      necessitated by plantar ulcerations and rising LFTs. Final pathology was C4d
      negative and without evidence of rejection, inflammation, or thrombotic
      microangiopathy. Thus, nearly 1-mo rejection-free survival has been achieved
      following LXT in two of four consecutive recipients, demonstrating that the
      porcine liver can support life in primates for several weeks and has encouraging
      potential for clinical application as a bridge to allotransplantation for
      patients with acute-on-chronic or fulminant hepatic failure.

PMID- 28489307
TI  - Non-alcoholic fatty liver and advanced fibrosis in the elderly: Results from a
      community-based Polish survey.
AB  - BACKGROUND & AIMS: Development of non-alcoholic fatty liver (NAFL) is dependent
      on metabolic factors occurring at an increased frequency with advancing age.
      Until now, few studies have explored the prevalence of NAFL in aged populations.
      Our study aimed to determine the prevalence of NAFL and advanced fibrosis in the
      elderly population participating in a national survey of a community-based
      elderly cohort. METHODS: A total of 3003 participants (mean age 79.6 years, 46.8%
      male) were enrolled in the study, after applying the following exclusion
      criteria: individuals younger than 65 years old (n=829) and those with positive
      serological biomarkers of HBV or HCV infection (n=391), chronic alcohol ingestion
      (n=727) or incomplete data records (n=745). Based on the fatty liver index (FLI),
      the participants were classified into three categories: FLI<30 (no NAFL),
      30<=FLI<60 (borderline) and FLI>=60 (NAFL). According to the non-alcoholic fatty
      liver disease (NAFLD) fibrosis score (NFS), the participants were divided into
      three advanced fibrosis risk categories: NFS<-1.455 (low risk), 
      1.455<=NFS<=0.676 (intermediate risk) and NFS>0.676 (high risk). RESULTS: The
      prevalence of NAFL in the general population was 37.2%; the prevalence reached
      51.4% in participants 65-70 years of age and decreased with advancing age
      (P<.0001). The prevalence of advanced fibrosis was 7.79% (14.8% in the NAFL
      population) and increased with advancing age (P<.005). CONCLUSIONS: The
      prevalence of NAFL and metabolically driven advanced fibrosis are relatively
      common in the elderly population, and these hepatic conditions run in adverse
      directions with advancing age.

PMID- 28489309
TI  - Isotropic three-dimensional T2 mapping of knee cartilage: Development and
      validation.
AB  - PURPOSE: 1) To implement a higher-resolution isotropic 3D T2 mapping technique
      that uses sequential T2 -prepared segmented gradient-recalled echo (Iso3DGRE)
      images for knee cartilage evaluation, and 2) to validate it both in vitro and in
      vivo in healthy volunteers and patients with knee osteoarthritis. MATERIALS AND
      METHODS: The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was
      developed on a clinical 3T MR scanner. Numerical simulations were performed to
      optimize the pulse sequence parameters. A phantom study was performed to validate
      the T2 estimation accuracy. The repeatability of the sequence was assessed in
      healthy volunteers (n = 7). T2 values were compared with those from a clinical
      standard 2D multislice multiecho (MSME) T2 mapping sequence in knees of healthy
      volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5).
      RESULTS: The numerical simulations resulted in 100 excitations per segment and an
      optimal radiofrequency (RF) excitation angle of 15 degrees . The phantom study
      demonstrated a good correlation of the technique with the reference standard
      (slope 0.9 +/- 0.05, intercept 0.2 +/- 1.7 msec, R2 >= 0.99). Repeated
      measurements of cartilage T2 values in healthy volunteers showed a coefficient of
      variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher
      cartilage T2 values (P < 0.03) in OA patients. Iso3DGRE precision was equal to
      that of the MSME T2 mapping in healthy volunteers, and significantly higher in OA
      (P = 0.01). CONCLUSION: This study successfully demonstrated that high-resolution
      isotropic 3D T2 mapping for knee cartilage characterization is feasible,
      accurate, repeatable, and precise. The technique allows for multiplanar
      reformatting and thus T2 quantification in any plane of interest. LEVEL OF
      EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371.

PMID- 28489308
TI  - Terminal Parent Phosphanide and Phosphinidene Complexes of Zirconium(IV).
AB  - The reaction of [Zr(TrenDMBS )(Cl)] [Zr1; TrenDMBS =N(CH2 CH2 NSiMe2 But )3 ]
      with NaPH2 gave the terminal parent phosphanide complex [Zr(TrenDMBS )(PH2 )]
      [Zr2; Zr-P=2.690(2) A]. Treatment of Zr2 with one equivalent of KCH2 C6 H5 and
      two equivalents of benzo-15-crown-5 ether (B15C5) afforded an unprecedented
      example (outside of matrix isolation) of a structurally authenticated transition
      metal terminal parent phosphinidene complex [Zr(TrenDMBS )(PH)][K(B15C5)2 ] [Zr3;
      Zr=P=2.472(2) A]. DFT calculations reveal a polarized-covalent Zr=P double bond,
      with a Mayer bond order of 1.48, and together with IR spectroscopic data also
      suggest an agostic-type Zr???HP interaction [?ZrPH =66.7 degrees ] which is
      unexpectedly similar to that found in cryogenic, spectroscopically observed
      phosphinidene species. Surprisingly, computational data suggest that the Zr=P
      linkage is similarly polarized, and thus as covalent, as essentially
      isostructural U=P and Th=P analogues.

PMID- 28489311
TI  - How do we measure childhood?

PMID- 28489312
TI  - Blowing the whistle: moral distress and advocacy for preterm infants and their
      families.

PMID- 28489313
TI  - In utero seizures revealing dentato-olivary dysplasia caused by SCN2A mutation.

PMID- 28489314
TI  - Unclassifiable pattern of hypopigmentation in a patient with mosaic partial 12p
      tetrasomy without Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome (PKS-#OMIM601803) is a multisystem developmental
      disorder typically due to the presence of an aneuploidy cell line, consisting of
      a supernumerary tetrasomic chromosomal marker (SCM) arisen from the short arm of
      chromosome 12 (12p isochromosome). The clinical phenotype, which is strictly
      related to the percentage and tissue distribution of aneuploid cells, is
      characterized by craniofacial dysmorphisms, pigmentary skin anomalies, limb
      shortening, congenital heart defects, diaphragmatic hernia, hypotonia,
      intellectual disability, and epilepsy. We report on a 4 year-old girl harboring a
      12p partial isochromosome, involving the PKS critical region, affecting about 70%
      of circulating lymphocytes, urine, and saliva cells and fibroblast from a
      hyperpigmented skin spot, and 100% of fibroblasts from a hypopigmented skin spot.
      Interestingly, despite the high proportion of affected cells this patient did not
      present with PKS, and a pattern of linear and patchy pigmentary mosaicism was the
      sole clinical manifestation. The present observation suggests that partial 12p
      SCM can also result in mild phenotypes, and its prevalence in the human
      population could have been underestimated. Accurate dermatologic evaluation could
      be a major handle for genetic testing.

PMID- 28489315
TI  - Mechanically-Guided Deterministic Assembly of 3D Mesostructures Assisted by
      Residual Stresses.
AB  - Formation of 3D mesostructures in advanced functional materials is of growing
      interest due to the widespread envisioned applications of devices that exploit 3D
      architectures. Mechanically guided assembly based on compressive buckling of 2D
      precursors represents a promising method, with applicability to a diverse set of
      geometries and materials, including inorganic semiconductors, metals, polymers,
      and their heterogeneous combinations. This paper introduces ideas that extend the
      levels of control and the range of 3D layouts that are achievable in this manner.
      Here, thin, patterned layers with well-defined residual stresses influence the
      process of 2D to 3D geometric transformation. Systematic studies through combined
      analytical modeling, numerical simulations, and experimental observations
      demonstrate the effectiveness of the proposed strategy through ~20 example cases
      with a broad range of complex 3D topologies. The results elucidate the ability of
      these stressed layers to alter the energy landscape associated with the
      transformation process and, specifically, the energy barriers that separate
      different stable modes in the final 3D configurations. A demonstration in a
      mechanically tunable microbalance illustrates the utility of these ideas in a
      simple structure designed for mass measurement.

PMID- 28489316
TI  - Streptomyces: An annotated selection of World Wide Web sites relevant to the
      topics in environmental microbiology.

PMID- 28489317
TI  - Pharmacogenomics of angiotensin receptor/neprilysin inhibitor and its long-term
      side effects.
AB  - The development of the promising agent sacubitril/valsartan, known as an
      angiotensin receptor blocker-neprilysin inhibitor (ARNI), to improve heart
      failure (HF) management, may benefit morbidity, mortality, and readmission rates
      in patients with HF. The PARADIGM-HF trial demonstrated that the ARNI can reduce
      morbidity and mortality in patients with heart failure with reduced ejection
      fraction (HFrEF), while ongoing PARAMOUNT and PARAGON-HF trials determined
      whether the ARNI has morbidity and mortality benefits in patients with heart
      failure with preserved ejection fraction (HFpEF). However, the risk of long-term
      side effects of the ARNI such as cognitive dysfunction or Alzheimer's disease
      (AD) remains unknown. In fact, neprilysin (NEP), encoded by NEP or MME gene, is a
      principal peptidase involved in the degradation of beta-amyloid (Abeta) protein.
      Several studies have demonstrated that polymorphisms of the NEP gene may be
      associated with AD and cerebral amyloid angiopathy (CAA). Pharmacogenomics, the
      study of variability in drug response due to genetic polymorphisms, can
      potentially explain the variability in the effect of the ARNI and their side
      effects. Therefore, we have attempted to highlight pharmacogenomic factors and
      potential long-term side effects of the ARNI. Physicians should carefully monitor
      elderly patients with genetic risk factors for AD and CAA. In the future, genetic
      testing and genomic testing for NEP polymorphisms may play an important role in
      monitoring long-term side effects in ARNI-treated HF patients.

PMID- 28489318
TI  - Janus Copper Mesh Film with Unidirectional Water Transportation Ability toward
      High Efficiency Oil/Water Separation.
AB  - Inspired by the special asymmetric wettability and controllable permeation
      function of cell membranes, we report a Janus nanostructured copper mesh film
      with unidirectional water transportation ability. Water can permeate from the
      hydrophobic side to the hydrophilic side, but is retained in the opposite
      direction. Notably, based on this special unidirectional water permeation
      property, both heavy oil/water mixtures (rhooil >rhowater ) and light oil/water
      mixtures (rhooil <rhowater ) can be separated. Additionally, the film
      demonstrates high separation efficiency and good recyclability. This paper
      reports a new Janus film that achieved highly efficient oil/water separation
      based on smart control of the wettability of the film. It is believed to have the
      potential to be used in many practical applications, such as wastewater treatment
      and oil-spill cleanup.

PMID- 28489319
TI  - Low physical activity as a key differentiating factor in the potential high-risk
      profile for depressive symptoms in older adults.
AB  - BACKGROUND: The identification of potential high-risk groups for depression is of
      importance. The purpose of the present study was to identify high-risk profiles
      for depressive symptoms in older individuals, with a focus on functional
      performance. METHODS: The population-based Healthy Ageing Initiative included
      2,084 community-dwelling individuals (49% women) aged 70. Explorative cluster
      analysis was used to group participants according to functional performance
      level, using measures of basic mobility skills, gait variability, and grip
      strength. Intercluster differences in depressive symptoms (measured by the
      Geriatric Depression Scale [GDS]-15), physical activity (PA; measured objectively
      with the ActiGraph GT3X+), and a rich set of covariates were examined. RESULTS:
      The cluster analysis yielded a seven-cluster solution. One potential high-risk
      cluster was identified, with overrepresentation of individuals with GDS scores >5
      (15.1 vs. 2.7% expected; relative risk = 6.99, P < .001); the prevalence of
      depressive symptoms was significantly lower in the other clusters (all P < .01).
      The potential high-risk cluster had significant overrepresentations of obese
      individuals (39.7 vs. 17.4% expected) and those with type 2 diabetes (24.7 vs.
      8.5% expected), and underrepresentation of individuals who fulfilled the World
      Health Organization's PA recommendations (15.6 vs. 59.1% expected; all P < .01),
      as well as low levels of functional performance. CONCLUSIONS: The present study
      provided a potential high-risk profile for depressive symptoms among elderly
      community-dwelling individuals, which included low levels functional performance
      combined with low levels of PA. Including PA in medical screening of the elderly
      may aid in identification of potential high-risk individuals for depressive
      symptoms.

PMID- 28489320
TI  - Role of cyclooxygenase in the vascular responses to extremity cooling in
      Caucasian and African males.
AB  - NEW FINDINGS: What is the central question of this study? Compared with
      Caucasians, African individuals are more susceptible to non-freezing cold injury
      and experience greater cutaneous vasoconstriction and cooler finger skin
      temperatures upon hand cooling. We investigated whether the enzyme cyclooxygenase
      is, in part, responsible for the exaggerated response to local cooling. What is
      the main finding and its importance? During local hand cooling, individuals of
      African descent experienced significantly lower finger skin blood flow and skin
      temperature compared with Caucasians irrespective of cyclooxygenase inhibition.
      These data suggest that in young African males the cyclooxygenase pathway appears
      not to be the primary reason for the increased susceptibility to non-freezing
      cold injury. Individuals of African descent (AFD) are more susceptible to non
      freezing cold injury (NFCI) and experience an exaggerated cutaneous
      vasoconstrictor response to hand cooling compared with Caucasians (CAU). Using a
      placebo-controlled, cross-over design, this study tested the hypothesis that
      cyclooxygenase (COX) may, in part, be responsible for the exaggerated
      vasoconstrictor response to local cooling in AFD. Twelve AFD and 12 CAU young
      healthy men completed foot cooling and hand cooling (separately, in 8 degrees C
      water for 30 min) with spontaneous rewarming in 30 degrees C air after placebo or
      aspirin (COX inhibition) treatment. Skin blood flow, expressed as cutaneous
      vascular conductance (as flux per millimetre of mercury), and skin temperature
      were measured throughout. Irrespective of COX inhibition, the responses to foot
      cooling, but not hand cooling, were similar between ethnicities. Specifically,
      during hand cooling after placebo, AFD experienced a lower minimal skin blood
      flow [mean (SD): 0.5 (0.1) versus 0.8 (0.2) flux mmHg-1 , P < 0.001] and a lower
      minimal finger skin temperature [9.5 (1.4) versus 10.7 (1.3) degrees C, P =
      0.039] compared with CAU. During spontaneous rewarming, average skin blood flow
      was also lower in AFD than in CAU [2.8 (1.6) versus 4.3 (1.0) flux mmHg-1 , P <
      0.001]. These data provide further support that AFD experience an exaggerated
      response to hand cooling on reflection this appears to overstate findings;
      however, the results demonstrate that the COX pathway is not the primary reason
      for the exaggerated responses in AFD and increased susceptibility to NFCI.

PMID- 28489321
TI  - Nicotine deprivation attenuates panic reactivity in smokers: Findings from a
      placebo-controlled nicotine patch study.
AB  - BACKGROUND: Prospective studies consistently find that smoking is a risk factor
      for the development of panic disorder (PD). A possible explanation is that
      nicotine deprivation promotes heightened sensitivity to bodily sensations and/or
      arterial carbon dioxide (CO2 ). Abrams et al. (2011) previously found that, in
      response to a CO2 rebreathing challenge, smokers experiencing more (vs. less)
      intense nicotine withdrawal had more severe panic symptoms and a stronger urge to
      escape. However, participants were aware of the last time they smoked, leaving
      unclear the extent to which fear reactivity was influenced by the pharmacologic
      effects of nicotine deprivation versus beliefs regarding when nicotine was most
      recently used. The present study aimed to ascertain whether nicotine deprivation,
      independent of beliefs regarding recent nicotine use, promotes fear reactivity
      among smokers. METHODS: Moderate to heavy smokers without PD (N = 25)
      participated in a placebo-controlled, double-blind study consisting of two
      sessions spaced 1 week apart. Participants abstained from nicotine for 2 hr prior
      to sessions. During one session participants were given a 21 mg nicotine
      replacement patch and, during the other, a placebo patch, with the order
      counterbalanced. For both sessions, after a 3-hr absorption period, participants
      underwent a 10-min CO2 rebreathing challenge. RESULTS: Wearing a nicotine (vs.
      placebo) patch increased self-reported panic reactivity among participants, but
      did not significantly affect physiological and behavioral measures of reactivity.
      CONCLUSIONS: In smokers without a history of PD, nicotine deprivation attenuates
      subjective panic reactivity. Possible explanations for the contrast between
      theory and laboratory findings as well as clinical implications are discussed.

PMID- 28489322
TI  - Developmental effects of androgens in the human brain.
AB  - Neuroendocrine theories of brain development posit that androgens play a crucial
      role in sex-specific cortical growth, although little is known about the
      differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico
      limbic development and cognition during adolescence. In this context, the
      National Institutes of Health Study of Normal Brain Development, a longitudinal
      study of typically developing children and adolescents aged 4-24 years (n=433),
      offers a unique opportunity to examine the developmental effects of androgens on
      cortico-limbic maturation and cognition. Using data from this sample, our group
      found that higher testosterone levels were associated with left-sided decreases
      in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal
      cortex, compared to right-sided increases in CTh in somatosensory areas in pre
      pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural
      covariance (considered to reflect structural connectivity) also varied according
      to testosterone levels, with the testosterone-related brain phenotype predicting
      higher aggression levels and lower executive function, particularly in boys. By
      contrast, DHEA was associated with a pre-pubertal increase in CTh of several
      regions involved in cognitive control in both boys and girls. Covariance within
      several cortico-amygdalar structural networks also varied as a function of DHEA
      levels, with the DHEA-related brain phenotype predicting improvements in visual
      attention in both boys and girls. DHEA-related cortico-hippocampal structural
      covariance, on the other hand, predicted higher scores on a test of working
      memory. Interestingly, there were significant interactions between testosterone
      and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of
      testosterone on brain structure. In sum, testosterone-related effects on the
      developing brain may lead to detrimental effects on cortical functions (ie,
      higher aggression and lower executive function), whereas DHEA-related effects may
      optimise cortical functions (ie, better attention and working memory), perhaps by
      decreasing the influence of amygdalar and hippocampal afferents on cortical
      functions.

PMID- 28489324
TI  - Executive summary of the SCAI/HFSA clinical expert consensus document on the use
      of invasive hemodynamics for the diagnosis and management of cardiovascular
      disease.

PMID- 28489323
TI  - Mild, moderate, meaningful? Examining the psychological and functioning
      correlates of DSM-5 eating disorder severity specifiers.
AB  - OBJECTIVE: This study evaluated the DSM-5 severity specifiers for treatment
      seeking groups of participants with anorexia nervosa (AN), the purging form of
      bulimia nervosa (BN), and binge-eating disorder (BED). METHOD: Hundred and sixty
      two participants with AN, 93 participants with BN, and 343 participants with BED
      were diagnosed using semi-structured interviews, sub-categorized using DSM-5
      severity specifiers and compared on demographic and cross-sectional clinical
      measures. RESULTS: In AN, the number of previous hospitalizations and the
      duration of illness increased with severity, but there was no difference across
      severity groups on measures of eating pathology, depression, or measures of self
      reported physical or emotional functioning. In BN, the level of eating concerns
      increased across the severity groups, but the groups did not differ on measures
      of depression, self-esteem, and most eating pathology variables. In BN, support
      was also found for an alternative severity classification scheme based upon
      number of methods of purging. In BED, levels of several measures of eating
      pathology and self-reported physical and emotional functioning increased across
      the severity groups. For BED, however, support was also found for an alternative
      severity classification scheme based upon overvaluation of shape and weight.
      Preliminary evidence was also found for a transdiagnostic severity index based
      upon overvaluation of shape and weight. DISCUSSION: Overall, these data show
      limited support for the DSM-5 severity specifiers for BN and modest support for
      the DSM-5 severity specifiers for AN and BED.

PMID- 28489325
TI  - Reducing Macro- and Microheterogeneity of N-Glycans Enables the Crystal Structure
      of the Lectin and EGF-Like Domains of Human L-Selectin To Be Solved at 1.9 A
      Resolution.
AB  - L-Selectin, a cell-adhesion receptor on the surface of most leukocytes, contains
      seven N-glycosylation sites. In order to obtain the crystal structure of human L
      selectin, we expressed a shortened version of L-selectin comprising the C-type
      lectin and EGF-like domains (termed LE) and systematically analysed mutations of
      the three glycosylation sites (Asn22, Asn66 and Asn139) in order to reduce
      macroheterogeneity. After we further removed microheterogeneity, we obtained
      crystals that diffracted X-rays up to 1.9 A from a variant (LE010) with exchanges
      N22Q and N139Q and one GlcNAc2 Man5 N-glycan chain attached to Asn66. Crystal
      structure analysis showed that the terminal mannose of GlcNAc2 Man5 of one LE010
      molecule was coordinated to Ca2+ in the binding site of a symmetry-related LE010.
      The orientation of the lectin and EGF-like domain was similar to the described
      "bent" conformation of E- and P-selectins. The Ca2+ -binding site reflects the
      binding mode seen in E- and P-selectin structures co-crystallised with ligands.

PMID- 28489326
TI  - Highly Selective Stable Isotope Labeling of Histidine Residues by Using a Novel
      Precursor in E. coli-Based Overexpression Systems.
AB  - The importance of NMR spectroscopy in unraveling the structural and dynamic
      properties of proteins is ever-expanding owing to progress in experimental
      techniques, hardware development, and novel labeling approaches. Multiple
      sophisticated methods of aliphatic residue labeling can be found in the
      literature, whereas the selective incorporation of NMR active isotopes into other
      amino acids still holds the potential for improvement. In order to close this
      methodological gap, we present a novel metabolic precursor for cell-based protein
      overexpression to assemble 13 C/2 H isotope patterns in the peptide backbone, as
      well as in side chain positions of a mechanistically distinguished histidine
      residue.

PMID- 28489328
TI  - Induction of Chondrogenic Differentiation of Human Mesenchymal Stem Cells by
      Biomimetic Gold Nanoparticles with Tunable RGD Density.
AB  - Nanostructured materials have drawn a broad attention for their applications in
      biomedical fields. Ligand-modified nanomaterials can well mimic the dynamic
      extracellular matrix (ECM) microenvironments to regulate cell functions and
      fates. Herein, ECM mimetic gold nanoparticles (Au NPs) with tunable surface
      arginine-glycine-aspartate (RGD) density are designed and synthesized to induce
      the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The
      biomimetic Au NPs with an average size of 40 nm shows good biocompatibility
      without affecting the cell proliferation in the studied concentration range. The
      RGD motifs on Au NPs surface facilitate cellular uptake of NPs into monolayer
      hMSCs through integrin-mediated endocytosis. The biomimetic NPs have a promotive
      effect on cartilaginous matrix production and marker gene expression in cell
      pellet culture, especially for the biomimetic Au NPs with high surface RGD
      density. This study provides a novel strategy for fabricating biomimetic NPs to
      regulate cell differentiation, which holds great potentials in tissue engineering
      and biomedical applications.

PMID- 28489327
TI  - New directions for the treatment of depression: Targeting the photic regulation
      of arousal and mood (PRAM) pathway.
AB  - Both preclinical and clinical studies demonstrate that depression is strongly
      associated with reduced light availability, which in turn contributes to
      decreased function of brain regions that control mood. Here, we review findings
      that support a critical pathway for the control of mood that depends upon ambient
      light. We put forward a novel hypothesis, functionally linking retina to locus
      coeruleus (LC) in depression, and discuss the role of norepinephrine in affective
      disease. Finally, we discuss how utilizing the chemogenetic tool Designer
      Receptors Exclusively Activated by Designer Drugs (DREADDs) to precisely control
      this retina-LC circuit may be used as a novel therapeutic to treat depression.

PMID- 28489329
TI  - Differential responses of soil bacteria, fungi, archaea and protists to plant
      species richness and plant functional group identity.
AB  - Plants are known to influence belowground microbial community structure along
      their roots, but the impacts of plant species richness and plant functional group
      (FG) identity on microbial communities in the bulk soil are still not well
      understood. Here, we used 454-pyrosequencing to analyse the soil microbial
      community composition in a long-term biodiversity experiment at Jena, Germany. We
      examined responses of bacteria, fungi, archaea, and protists to plant species
      richness (communities varying from 1 to 60 sown species) and plant FG identity
      (grasses, legumes, small herbs, tall herbs) in bulk soil. We hypothesized that
      plant species richness and FG identity would alter microbial community
      composition and have a positive impact on microbial species richness. Plant
      species richness had a marginal positive effect on the richness of fungi, but we
      observed no such effect on bacteria, archaea and protists. Plant species richness
      also did not have a large impact on microbial community composition. Rather,
      abiotic soil properties partially explained the community composition of
      bacteria, fungi, arbuscular mycorrhizal fungi (AMF), archaea and protists. Plant
      FG richness did not impact microbial community composition; however, plant FG
      identity was more effective. Bacterial richness was highest in legume plots and
      lowest in small herb plots, and AMF and archaeal community composition in legume
      plant communities was distinct from that in communities composed of other plant
      FGs. We conclude that soil microbial community composition in bulk soil is
      influenced more by changes in plant FG composition and abiotic soil properties,
      than by changes in plant species richness per se.

PMID- 28489330
TI  - Comment on "Flexible Asymmetric Supercapacitors Based on Nitrogen-Doped Graphene
      Hydrogels with Embedded Nickel Hydroxide Nanoplates".
AB  - It is argued that the main claims of "Flexible Asymmetric Supercapacitors Based
      on Nitrogen-Doped Graphene Hydrogels with Embedded Nickel Hydroxide Nanoplates"
      are strongly exaggerated. By selecting first a subregion (DeltaV) of the total
      voltage drop, the capacitance (CDeltaV ) is inflated by 30 %. Then, by selecting
      different regions for different properties and using different DeltaV values in
      different terms of a single expression for the energy density (EDeltaV ), the
      value is doubled. A bending angle of only 45 degrees  is instead claimed to be
      180 degrees .

PMID- 28489331
TI  - SCAI/HFSA clinical expert consensus document on the use of invasive hemodynamics
      for the diagnosis and management of cardiovascular disease.

PMID- 28489332
TI  - Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators.
AB  - A deeper understanding of biological materials and the design principles that
      govern them, combined with the enabling technology of 3D printing, has given rise
      to the idea of "building with biology." Using these materials and tools, bio
      hybrid robots or bio-bots, which adaptively sense and respond to their
      environment, can be manufactured. Skeletal muscle bioactuators are developed to
      power these bio-bots, and an approach is presented to make them dynamically
      responsive to changing environmental loads and robustly resilient to induced
      damage. Specifically, since the predominant cause of skeletal muscle loss of
      function is mechanical damage, the underlying mechanisms of damage are
      investigated in vitro, and an in vivo inspired healing strategy is developed to
      counteract this damage. The protocol that is developed yields complete recovery
      of healthy tissue functionality within two days of damage, setting the stage for
      a more robust, resilient, and adaptive bioactuator technology than previously
      demonstrated. Understanding and exploiting the adaptive response behaviors
      inherent within biological systems in this manner is a crucial step forward in
      designing bio-hybrid machines that are broadly applicable to grand engineering
      challenges.

PMID- 28489333
TI  - Highly Efficient and Uniform 1 cm2 Perovskite Solar Cells with an
      Electrochemically Deposited NiOx Hole-Extraction Layer.
AB  - Given that the highest certified conversion efficiency of the organic-inorganic
      perovskite solar cell (PSC) already exceeds 22 %, which is even higher than that
      of the polycrystalline silicon solar cell, the significance of new scalable
      processes that can be utilized for preparing large-area devices and their
      commercialization is rapidly increasing. From this perspective, the
      electrodeposition method is one of the most suitable processes for preparing
      large-area devices because it is an already commercialized process with proven
      controllability and scalability. Here, a highly uniform NiOx layer prepared by
      electrochemical deposition is reported as an efficient hole-extraction layer of a
      p-i-n-type planar PSC with a large active area of >1 cm2 . It is demonstrated
      that the increased surface roughness of the NiOx layer, achieved by controlling
      the deposition current density, facilitates the hole extraction at the interface
      between perovskite and NiOx , and thus increases the fill factor and the
      conversion efficiency. The electrochemically deposited NiOx layer also exhibits
      extremely uniform thickness and morphology, leading to highly efficient and
      uniform large-area PSCs. As a result, the p-i-n-type planar PSC with an area of
      1.084 cm2 exhibits a stable conversion efficiency of 17.0 % (19.2 % for 0.1 cm2 )
      without showing hysteresis effects.

PMID- 28489334
TI  - Diagnosis of CoPAN by whole exome sequencing: Waking up a sleeping tiger's eye.
AB  - Neurodegeneration with brain iron accumulation (NBIA) is a group of
      neurodegenerative disorders characterized by iron accumulation in the basal
      ganglia. Recently, mutations in CoA synthase (COASY) have been identified as a
      cause of a novel NBIA subtype (COASY Protein-Associated Neurodegeneration, CoPAN)
      in two patients with dystonic paraparesis, parkinsonian features, cognitive
      impairment, behavior abnormalities, and axonal neuropathy. COASY encodes an
      enzyme required for Coenzyme A (CoA) biosynthesis. Using whole exome sequencing
      (WES) we identified compound heterozygous COASY mutations in two siblings with
      intellectual disability, ataxic gait, progressive spasticity, and obsessive
      compulsive behavior. The "eye-of-the tiger-sign," a characteristic hypointense
      spot within the hyperintense globi pallidi on MRI found in the most common
      subtype of NBIA (Pantothenate Kinase-Associated Neurodegeneration, PKAN), was not
      present. Instead, bilateral hyperintensity and swelling of caudate nucleus,
      putamen, and thalamus were found. In addition, our patients showed a small corpus
      callosum and frontotemporal and parietal white matter changes, expanding the
      brain phenotype of patients with CoPAN. Metabolic investigations showed increased
      free carnitine and decreased acylcarnitines in the patients dried blood samples.
      Carnitine palmitoyl transferase 1 (CPT1) deficiency was excluded by further
      enzymatic and metabolic investigations. As CoA and its derivate Acetyl-CoA play
      an essential role in fatty acid metabolism, we assume that abnormal acylcarnitine
      profiles are a result of the COASY mutations. This report not only illustrates
      that WES is a powerful tool to elucidate the etiology of rare genetic diseases,
      but also identifies unique neuroimaging and metabolic findings that may be key
      features for an early diagnosis of CoPAN.

PMID- 28489335
TI  - Phacomatosis pigmentokeratotica and precocious puberty associated with HRAS
      mutation.

PMID- 28489336
TI  - Antimicrobial activity of natural products against Clostridium difficile in
      vitro.
AB  - AIMS: To investigate the antimicrobial activity of various natural products
      against Clostridium difficile in vitro. METHODS AND RESULTS: The antibacterial
      activity of 20 natural products was determined by the agar well diffusion and
      broth microdilution assays against four C. difficile strains, three comparator
      organisms and four gastrointestinal commensal organisms. Of the raw natural
      products, garlic juice had the highest activity. The most active processed
      products were peppermint oil and the four pure compounds trans-cinnamaldehyde,
      allicin, menthol and zingerone. Furthermore, Bacteroides species had similar
      susceptibility to C. difficile to most natural products; however, Lactobacillus
      casei was less susceptible. The combined effect of natural products with
      vancomycin or metronidazole was determined using the conventional checkerboard
      titration method and the fractional inhibitory concentration index was
      calculated. The results showed a possible synergism between trans-cinnamaldehyde
      and vancomycin and partial synergy between trans-cinnamaldehyde and
      metronidazole. CONCLUSIONS: The study indicates a range of antimicrobial activity
      of natural products against C. difficile and suggests that they may be useful as
      alternative or complementary treatments for C. difficile infection (CDI),
      particularly as most are able to be given orally. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study encourages further investigation of natural products for
      treatment of CDI.

PMID- 28489337
TI  - Quality of randomized controlled trials in eating disorder prevention.
AB  - OBJECTIVE: To investigate the quality of randomized controlled trials (RCTs) of
      eating disorder prevention. METHOD: A systematic literature search was conducted
      in Medline, PsycINFO, Embase, Scopus, and the Cochrane Collaboration Library to
      January 2016. Studies were included if they were RCTs that tested an eating
      disorder prevention program. We identified 96 studies with a total 15,350
      participants (91% female, M age = 17 years) and rated quality with the Quality
      Rating Scale (QRS; Moncrieff et al., 2001). RESULTS: The mean QRS score was 62%
      (SD = 13%). Several standards of quality were not frequently fulfilled (i.e.,
      failed to achieve an optimal rating), for example, power calculation (85%),
      intent-to-treat analysis (54%), blinding of assessor (75%), representative sample
      (78%), adequate sample size (75%), and appropriate duration of trial including
      follow-up (67%). QRS was positively and significantly associated with publication
      year, number of authors, and PubMed-indexation. DISCUSSION: Given the majority of
      eating disorder prevention studies had problems with trial quality, it is
      recommended that future RCTs follow quality checklists and CONSORT guidelines,
      that RCTs are registered, and protocols published in advance. In addition,
      funding bodies are called on to deliver the support needed to ensure that
      preventions for eating disorders are efficiently and cost-effectively achieved.

PMID- 28489338
TI  - Regulatory T Cells Promote Natural Killer Cell Education in Mixed Chimeras.
AB  - Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of
      conventional doses of allogeneic bone marrow (BM) in nonirradiated recipient mice
      conditioned with costimulation blockade and mammalian target of rapamycin
      inhibition. The mode of action responsible for this Treg effect is poorly
      understood but may encompass the control of costimulation blockade-resistant
      natural killer (NK) cells. We show that transient NK cell depletion at the time
      of BM transplantation led to BM engraftment and persistent chimerism without Treg
      transfer but failed to induce skin graft tolerance. In contrast, the permanent
      absence of anti-donor NK reactivity in mice grafted with F1 BM was associated
      with both chimerism and tolerance comparable to Treg therapy, implying that NK
      cell tolerization is a critical mechanism of Treg therapy. Indeed, NK cells of
      Treg-treated BM recipients reshaped their receptor repertoire in the presence of
      donor MHC in a manner suggesting attenuated donor reactivity. These results
      indicate that adoptively transferred Tregs prevent BM rejection, at least in
      part, by suppressing NK cells and promote tolerance by regulating the appearance
      of NK cells expressing activating receptors to donor class I MHC.

PMID- 28489339
TI  - De novo IGF2 mutation on the paternal allele in a patient with Silver-Russell
      syndrome and ectrodactyly.
AB  - Although paternally expressed IGF2 is known to play a critical role in placental
      and body growth, only a single mutation has been found in IGF2. We identified,
      through whole-exome sequencing, a de novo IGF2 indel mutation leading to
      frameshift (NM_000612.5:c.110_117delinsAGGTAA, p.(Leu37Glnfs*31)) in a patient
      with Silver-Russell syndrome, ectrodactyly, undermasculinized genitalia,
      developmental delay, and placental hypoplasia. Furthermore, we demonstrated that
      the mutation resided on the paternal allele by sequencing the long PCR product
      harboring the mutation- and methylation-sensitive SmaI and SalI sites before and
      after SmaI/SalI digestion. The results, together with the previous findings in
      four cases from a single family with a paternally inherited IGF2 nonsense
      mutation and those in patients with variable H19 differentially methylated region
      epimutations leading to compromised IGF2 expression, suggest that the whole
      phenotype of this patient is explainable by the IGF2 mutation, and that
      phenotypic severity is primarily determined by the IGF2 expression level in
      target tissues.

PMID- 28489340
TI  - Comment: obesity as a disease - some implications for the World Obesity
      Federation's advocacy and public health activities.

PMID- 28489342
TI  - pH-Sensitive Reversible Programmed Targeting Strategy by the Self
      Assembly/Disassembly of Gold Nanoparticles.
AB  - A reversible programmed targeting strategy could achieve high tumor accumulation
      due to its long blood circulation time and high cellular internalization. Here,
      targeting ligand-modified poly(ethylene glycol) (PEG-ligand), dibutylamines (Bu),
      and pyrrolidinamines (Py) were introduced on the surface of gold nanoparticles
      (Au NPs) for reversible shielding/deshielding of the targeting ligands by pH
      responsive self-assembly. Hydrophobic interaction and steric repulsion are the
      main driving forces for the self-assembly/disassembly of Au NPs. The precise self
      assembly (pH >= 7.2) and disassembly (pH <= 6.8) of Au NPs with different ligands
      could be achieved by fine-tuning the modifying molar ratio of Bu and Py (Rm),
      which followed the formula Rm = 1/(-0.0013X2 + 0.0323X + 1), in which X is the
      logarithm of the partition coefficient of the targeting ligand. The
      assembled/disassembled behavior of Au NPs at pH 7.2 and 6.8 was confirmed by
      transmission electron microscopy and dynamic light scattering. Enzyme-linked
      immunosorbent assays and cellular uptake studies showed that the ligands could be
      buried inside the assembly and exposed when disassembled. More importantly, this
      process was reversible, which provides the possibility of prolonging blood
      circulation by shielding ligands associated with the NPs that were effused from
      tumor tissue.

PMID- 28489341
TI  - Smart Asymmetric Vesicles with Triggered Availability of Inner Cell-Penetrating
      Shells for Specific Intracellular Drug Delivery.
AB  - Smart nanocarriers attract considerable interest in the filed of precision
      nanomedicine. Dynamic control of the interaction between nanocarriers and cells
      offers the feasibility that in situ activates cellular internalization at the
      targeting sites. Herein, we demonstrate a novel class of enzyme-responsive
      asymmetric polymeric vesicles self-assembled from matrix metalloproteinase (MMP)
      cleavable peptide-linked triblock copolymer, poly(ethylene glycol)-GPLGVRG-b
      poly(epsilon-caprolactone)-b-poly(3-guanidinopropyl methacrylamide) (PEG-GPLGVRG
      PCL-PGPMA), in which the cell-penetrating PGPMA segments asymmetrically
      distribute in the outer and inner shells with fractions of 9% and 91%,
      respectively. Upon treatment with MMP-2 to cleave the stealthy PEG shell, the
      vesicles undergo morphological transformation into fused multicavity vesicles and
      small nanoparticles, accompanied by redistribution of PGPMA segments with 76%
      exposed to the outside. The vesicles after dePEGylation show significantly
      increased cellular internalization efficiency (~10 times) as compared to the
      original ones due to the triggered availability of cell-penetrating shells. The
      vesicles loading hydrophobic anticancer drug paclitaxel (PTX) in the membrane
      exhibit significantly enhanced cytotoxicity against MMP-overexpressing HT1080
      cells and multicellular spheroids. The proposed vesicular system can serve as a
      smart nanoplatform for in situ activating intracellular drug delivery in MMP
      enriched tumors.

PMID- 28489343
TI  - Rearranged Biosynthetic Gene Cluster and Synthesis of Hassallidin E in
      Planktothrix serta PCC 8927.
AB  - Cyanobacteria produce a wide range of natural products with antifungal
      bioactivity. The cyclic glycosylated lipopeptides of the hassallidin family have
      potent antifungal activity and display a great degree of chemical diversity.
      Here, we report the discovery of a hassallidin biosynthetic gene cluster from the
      filamentous cyanobacterium Planktothrix serta PCC 8927. The hassallidin gene
      cluster showed heavy rearrangement and marks of genomic plasticity. Nucleotide
      bias, differences in GC content, and phylogenetic incongruence suggested the
      acquisition of the hassallidin biosynthetic gene cluster in Planktothrix serta
      PCC 8927 by horizontal gene transfer. Chemical analyses by liquid chromatography
      and mass spectrometry demonstrated that this strain produced hassallidin E, a new
      glycosylated hassallidin variant. Hassallidin E was the only structural variant
      produced by Planktothrix serta PCC 8927 in all tested conditions. Further
      evaluated on human pathogenic fungi, hassallidin E showed an antifungal
      bioactivity. Hassallidin production levels correlated with nitrogen availability,
      in the only nitrogen-fixing Planktothrix described so far. Our results provide
      insights into the distribution and chemical diversity of cyanobacterial
      antifungal compounds as well as raise questions on their ecological relevance.

PMID- 28489344
TI  - In Situ Engineering Toward Core Regions: A Smart Way to Make Applicable
      FeF3@Carbon Nanoreactor Cathodes for Li-Ion Batteries.
AB  - Iron fluorides (FeFx) have attracted great interest in Li-ion batteries due to
      their high theoretical capacity, low cost, and preferable cell safety. However,
      their practical utilization is severely impeded by inferior electrode kinetics,
      leading to poor electrode cyclability and rate capabilities. The major bottleneck
      should be lack of any effective engineering techniques to make reliable
      encapsulation and conducting matrix on soluble FeFx species. Herein, we propose
      an applicable synthetic strategy where the massive production of FeF3@carbon
      nanoreactors (total size: ~60 nm) can be easily achieved by in situ engineering
      toward the core regions in hybrids, with the iron rust wastes and common solvents
      as raw materials. Such functionalized configurations can well make up for the
      shortcomings of FeF3 species, enabling them with outstanding cathode behaviors
      involving excellent reversible capacity retention (~270% higher than that of a
      bare FeF3 electrode after 600 cycles) and drastically enhanced rate performance.
      This paradigm work provides a facile and scalable method to make superior and
      sustainable cathodes and, moreover, offers a feasible engineering protocol to
      make water-soluble species encapsulated into carbon matrix, not merely for
      batteries but also for other wide range of fields like catalysis, nanomedicine,
      etc.

PMID- 28489345
TI  - Orthogonal Liquid Crystal Alignment Layer: Templating Speed-Dependent Orientation
      of Chromonic Liquid Crystals.
AB  - Lyotropic chromonic liquid crystals (LCLCs) have been extensively studied because
      of the interesting structural characteristics of the linear aggregation of their
      plank-shaped molecules in aqueous solvents. We report a simple method to control
      the orientation of LCLCs such as Sunset Yellow (SSY), disodium cromoglycate
      (DSCG), and DNA by varying pulling speed of the top substrate and temperatures
      during shear flow induced experiment. Crystallized columns of LCLCs are aligned
      parallel and perpendicular to the shear direction, at fast and slow pulling
      speeds of the top substrate, respectively. On the basis of this result, we
      fabricated an orthogonally patterned film that can be used as an alignment layer
      for guiding rodlike liquid crystals (LCs) to generate both twisted and planar
      alignments simultaneously. Our resulting platform can provide a facile method to
      form multidirectional orientation of soft materials and biomaterials in a process
      of simple shearing and evaporation, which gives rise to potential patterning
      applications using LCLCs due to their unique structural characteristics.

PMID- 28489346
TI  - Metal-Organic Frameworks at the Biointerface: Synthetic Strategies and
      Applications.
AB  - Many living organisms are capable of producing inorganic materials of precisely
      controlled structure and morphology. This ubiquitous process is termed
      biomineralization and is observed in nature from the macroscale (e.g., formation
      of exoskeletons) down to the nanoscale (e.g., mineral storage and transportation
      in proteins). Extensive research efforts have pursued replicating this chemistry
      with the overarching aims of synthesizing new materials of unprecedented physical
      properties and understanding the complex mechanisms that occur at the biological
      inorganic interface. Recently, we demonstrated that a class of porous materials
      termed metal-organic frameworks (MOFs) can spontaneously form on protein-based
      hydrogels via a process analogous to natural matrix-mediated biomineralization.
      Subsequently, this strategy was extended to functional biomacromolecules,
      including proteins and DNA, which have been shown to seed and accelerate
      crystallization of MOFs. Alternative strategies exploit co-precipitating agents
      such as polymers to induce MOF particle formation thus facilitating protein
      encapsulation within the porous crystals. In these examples the rigid molecular
      architecture of the MOF was found to form a protective coating around the
      biomacromolecule offering improved stability to external environments that would
      normally lead to its degradation. In this way, the MOF shell mimics the
      protective function of a biomineralized exoskeleton. Other methodologies have
      also been explored to encapsulate enzymes within MOF structures, including the
      fabrication of polycrystalline hollow MOF microcapsules that preserve the
      original enzyme functionality over several batch reaction cycles. The potential
      to design MOFs of varied pore size and chemical functionality has underpinned
      studies describing the postsynthesis infiltration of enzymes into MOF pore
      networks and bioconjugation strategies for the decoration of the MOF outer
      surface, respectively. These methods and configurations allow for customized
      biocomposites. MOF biocomposites have been extended from simple proteins to
      complex biological systems including viruses, living yeast cells, and bacteria.
      Indeed, a noteworthy result was that cells encapsulated within a crystalline MOF
      shell remain viable after exposure to a medium containing lytic enzymes.
      Furthermore, the cells can adsorb nutrients (glucose) through the MOF shell but
      cease reproducing until the MOF casing is removed, at which point normal cellular
      activity is fully restored. The field of MOF biocomposites is expansive and
      rapidly developing toward different applied research fields including protection
      and delivery of biopharmaceuticals, biosensing, biocatalysis, biobanking, and
      cell and virus manipulation. This Account describes the current progress of MOFs
      toward biotechnological applications highlighting the different strategies for
      the preparation of biocomposites, the developmental milestones, the challenges,
      and the potential impact of MOFs to the field.

PMID- 28489347
TI  - Measurement of the Density of Engineered Silver Nanoparticles Using Centrifugal
      FFF-TEM and Single Particle ICP-MS.
AB  - A methodology has been developed to measure nanoparticle mass and density, by
      combining centrifugal field-flow fractionation (CeFFF; more commonly called
      sedimentation FFF or SdFFF) and transmission electron microscopy (TEM). Particle
      effective mass obtained from CeFFF retention data and particle size obtained from
      the TEM images were used to calculate the nanoparticle density. The method was
      initially applied to measure the density of monodispersed polystyrene latex
      nanoparticles. Measured densities for latex nanoparticles of 160-300 nm in
      diameter were in the range of 1041-1063 kg m-3 with standard deviations of 0.6
      1.1%. Densities of engineered silver nanoparticles with nominal diameters of 30,
      60, 75, and 100 nm were measured using this methodology. For all four silver
      nanoparticle samples, the measured densities were 18-24% lower than the nominal
      density of metallic silver, with an overall mean value of 7900 +/- 675 kg m-3.
      Density values calculated using nanoparticle mass values obtained from single
      particle inductively coupled plasma-mass spectrometry (spICP-MS) measurements,
      corroborated the CeFFF-TEM results. The difference in the density of the silver
      nanoparticles compared to that of bulk silver suggests that the synthesis process
      could impart 20-37% porosity in silver nanoparticles. The data has important
      implications in the fields of nanomaterial, nanomedicine and nanotoxicology,
      where assumption of the bulk density for nanoparticles can result in erroneous
      estimation of parameters such as mass, size, porosity, and dosage. The presented
      methodology provides a straightforward and reproducible means for measurement of
      the density and porosity of engineered nanoparticles with a wide range of density
      and size.

PMID- 28489348
TI  - Novel Curcumin Liposome Modified with Hyaluronan Targeting CD44 Plays an Anti
      Leukemic Role in Acute Myeloid Leukemia in Vitro and in Vivo.
AB  - Curcumin has been widely used as a food additive for centuries and has been
      recently explored for its anti-inflammatory and antitumor properties. Although
      curcumin is pharmacologically safe and efficacious to certain cancers, its role
      against acute myeloid leukemia (AML) still remains unclear, and it lacks clinical
      application due to low water solubility and low in vivo bioavailability. To
      address these issues, we developed a novel curcumin liposome modified with
      hyaluronan (HA-Cur-LPs) to specifically deliver curcumin to AML by targeting CD44
      on AML cell surface. When compared with free curcumin and nontargeted liposome
      (Cur-LPs), the HA-Cur-LPs exhibited good stability, high affinity to CD44,
      increased cellular uptake, and more potent activity on inhibiting AML cell
      proliferation. The KG-1 cell implanted AML mice had significantly delayed, or
      even prevented, AML progression following treatment with 50 mg/kg of curcumin
      dose in the HA-Cur-LPs every 2 days for 2 weeks. Mechanistically, the anti-AML
      effects of HA-Cur-LPs were achieved by inhibiting Akt/ERK pathways and activating
      caspase-dependent apoptosis. Moreover, HA-Cur-LPs played a critical role in
      downregulation of DNMT1 expression in AML, leading to DNA hypomethylation and
      reactivation of tumor suppressor genes such as miR-223. The development and
      assessment of the HA-Cur-LPs in this study provide another potential choice for
      AML therapy, using HA-Cur-LPs as either a single treatment agent or in
      combination with other treatments.

PMID- 28489349
TI  - Wastewater for Urban Agriculture: A Significant Factor in Dissemination of
      Antibiotic Resistance.

PMID- 28489350
TI  - The Consequences of Nonrandomness in Species-Sensitivity in Relation to
      Functional Traits for Ecosystem-Level Effects of Chemicals.
AB  - Estimating ecosystem-level effects from single-species bioassays is a major
      challenge in environmental risk assessment. Most extrapolation procedures are
      based on the implicit assumption that species sensitivities are random with
      regard to their functional traits. Here, we explore how nonrandomness in species
      sensitivities affects how species-level and ecosystem level effects of chemical
      exposure correspond. The effect of a correlation between the trait value under
      control conditions and the sensitivity of the trait to chemical stress is studied
      for two traits (per capita growth rate and monoculture yield) under constant and
      temporary exposure. Theoretical model predictions are thereby validated against a
      3-week microcosm experiment, in which eight marine diatoms systems with different
      correlations between trait values and sensitivities were temporary (1 week) or
      constantly (3 weeks) exposed to two concentrations of the herbicide atrazine (100
      and 250 MUg L-1). Negative correlations increased the reduction in ecosystem
      functioning (productivity) by atrazine for both traits. However, correlations in
      the per capita growth rate affected productivity only shortly following changes
      in environmental conditions, whereas correlations in the monoculture yield
      affected productivity throughout exposure. Correlations between species
      sensitivities and functional trait values can thus help to identify when
      ecosystem-level effects are likely to exceed species-level effects.

PMID- 28489351
TI  - Nickel-Catalyzed Reductive Dicarbofunctionalization of Alkenes.
AB  - An intermolecular, three-component reductive dicarbofunctionalization of alkenes
      is presented here. The combination of Ni catalysis with TDAE as final reductant
      enables the direct formation of Csp3-Csp3 and Csp3-Csp2 bonds across a variety of
      pi-systems using two different electrophiles that are sequentially activated with
      exquisite selectivity under mild reaction conditions.

PMID- 28489352
TI  - Molecular Characterization of Nitrogen-Containing Organic Compounds in Humic-like
      Substances Emitted from Straw Residue Burning.
AB  - The molecular composition of humic-like substances (HULIS) in different aerosol
      samples was analyzed using an ultrahigh-resolution mass spectrometer to
      investigate the influence of biomass burning on ambient aerosol composition.
      HULIS in background aerosols were characterized with numerous molecular formulas
      similar to biogenic secondary organic aerosols. The abundance of nitrogen
      containing organic compounds (NOC), including nitrogen-containing bases (N-bases)
      and nitroaromatics, increased dramatically in ambient aerosols affected by crop
      residue burning in the farm field. The molecular distribution of N-bases in these
      samples exhibited similar patterns to those observed in smoke particles freshly
      emitted from lab-controlled burning of straw residues but were significantly
      different with those observed from wood burning. Signal intensity of the major N
      bases correlated well with the atmospheric concentrations of potassium and
      levoglucosan. These N-bases can serve as molecular markers distinguishing HULIS
      from crop residue burning with from wood burning. More nitroaromatics were
      detected in ambient aerosols affected by straw burning than in fresh smoke
      aerosols, indicating that many of them are formed in secondary oxidation
      processes as smoke plumes evolve in the atmosphere. This study highlights the
      significant contribution of crop residue burning to atmospheric NOC. Further
      study is warranted to evaluate the roles of NOC on climate and human health.

PMID- 28489353
TI  - Tailoring Thermoelectric Properties through Structure and Morphology in
      Chemically Synthesized n-Type Bismuth Telluride Nanostructures.
AB  - Here, we report a simple, cost-effective, surfactant-assisted, and aqueous-based
      low-temperature reflux method for the synthesis of Bi2Te3 nanocrystals.
      Thermoelectric properties of n-type bismuth telluride (BT) nanostructures are
      reported by varying the morphology and crystal structure. Tuning the reaction
      time from 1 to 36 h enables the phase transformation from BiTe with a hexagonal
      crystal structure to Bi2Te3 with a rhombohedral crystal structure, which is
      evident from the refined X-ray diffraction results and high-resolution
      transmission electron microscopy analysis. A perfect stoichiometric balance is
      achieved for all the compositions, and temperature variation of the electrical
      resistivity of all BT nanostructures shows the typical metal to semiconducting
      transition near room temperature. Seebeck coefficient and Hall measurements
      confirm electrons as the majority carriers and show the typical characteristics
      of n-type BT nanostructures. The nanocrystals inherited from the optimized
      reaction conditions and high densification of nanoparticle interfaces contribute
      to the considerable reduction of thermal conductivity in BT nanostructures.
      Highly crystalline, uniformly distributed nanocrystals of Bi2Te3 formed for 24 h
      reaction time demonstrate a promising figure of merit of 0.81 at 350 K, which can
      be attributed to their low thermal conductivity while the high electrical
      conductivity is maintained. Our research could provide new possibilities in low
      temperature synthesis where structural, compositional, and morphological tuning
      of BT nanostructures could promote practical thermoelectric applications near
      room temperature.

PMID- 28489354
TI  - A Biphilic Phosphetane Catalyzes N-N Bond-Forming Cadogan Heterocyclization via
      PIII/PV?O Redox Cycling.
AB  - A small-ring phosphacycle, 1,2,2,3,4,4-hexamethylphosphetane, is found to
      catalyze deoxygenative N-N bond-forming Cadogan heterocyclization of o
      nitrobenzaldimines, o-nitroazobenzenes, and related substrates in the presence of
      hydrosilane terminal reductant. The reaction provides a chemoselective catalytic
      synthesis of 2H-indazoles, 2H-benzotriazoles, and related fused heterocyclic
      systems with good functional group compatibility. On the basis of both
      stoichiometric and catalytic mechanistic experiments, the reaction is proposed to
      proceed via catalytic PIII/PV?O cycling, where DFT modeling suggests a turnover
      limiting (3+1) cheletropic addition between the phosphetane catalyst and
      nitroarene substrate. Strain/distortion analysis of the (3+1) transition
      structure highlights the controlling role of frontier orbital effects
      underpinning the catalytic performance of the phosphetane.

PMID- 28489355
TI  - Conjugate of an IgG Binding Domain with Botulinum Neurotoxin A Lacking the
      Acceptor Moiety Targets Its SNARE Protease into TrkA-Expressing Cells When
      Coupled to Anti-TrkA IgG or Fc-betaNGF.
AB  - Numerous naturally occurring toxins can perturb biological systems when they
      invade susceptible cells. Coupling of pertinent targeting ligands to the active
      domains of such proteins provides a strategy for directing these to particular
      cellular populations implicated in disease. A novel approach described herein
      involved fusion of one mutated immunoglobulin G (IgG) binding moiety of
      staphylococcal protein A to the SNARE protease and translocation domain of
      botulinum neurotoxin A (BoNT/A). This chimera could be monovalently coupled to
      IgG or via its Fc region to recombinant targeting ligands. The utility of the
      resulting conjugates is demonstrated by the delivery of a SNARE protease into a
      cell line expressing tropomyosin receptor kinase A (TrkA) through coupling to
      anti-TrkA IgG or a fusion of Fc and nerve-growth factor. Thus, this is a
      versitile and innovative technology for conjugating toxins to diverse ligands for
      retargeted cell delivery of potential therapeutics.

PMID- 28489356
TI  - Think Negative: Finding the Best Electrospray Ionization/MS Mode for Your
      Analyte.
AB  - For the first time, the electrospray ionization efficiency (IE) scales in
      positive and negative mode are united into a single system enabling direct
      comparison of IE values across ionization modes. This is made possible by the use
      of a reference compound that ionizes to a similar extent in both positive and
      negative modes. Thus, choosing the optimal (i.e., most sensitive) ionization
      conditions for a given set of analytes is enabled. Ionization efficiencies of 33
      compounds ionizing in both modes demonstrate that, contrary to general practice,
      negative mode allows better sensitivity for 46% of such compounds whereas the
      positive mode is preferred for only 18%, and for 36%, the results for both modes
      are comparable.

PMID- 28489357
TI  - Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive
      Detection of Gaseous HF.
AB  - Sensitive detection of harmful chemicals in industrial applications is pertinent
      to safety. In this work, we demonstrate the use of a sensitive silicon
      microcantilever (MC) system with a porous silicon oxide layer deposited on the
      active side of the MCs that have been mechanically manipulated to increase
      sensitivity. Included is the evaluation of porous silicon oxide present on
      different geometries of MCs and exposed to varying concentrations of hydrogen
      fluoride in humid air. Profilometry and the signal generated by the stress
      induced porous silicon oxide (PSO) coating and bending of the MC were used as
      methods of evaluation.

PMID- 28489358
TI  - Reactions of Platinum Carbonyl Chini Clusters with Ag(NHC)Cl Complexes: Formation
      of Acid-Base Lewis Adducts and Heteroleptic Clusters.
AB  - The reactions of anionic platinum carbonyl Chini clusters [Pt3n(CO)6n]2- [n = 2
      (1), 3 (2), 4 (3)] with Ag(IPr)Cl [IPr = C3N2H2(C6H3iPr2)2] afford the neutral
      acid-base Lewis adducts [Pt9(CO)18(AgIPr)2] (4) and [Pt6(CO)12(AgIPr)2] (5).
      These are thermally transformed into the homometallic heteroleptic neutral
      cluster [Pt3(CO)4(IPr)2] (6). Alternatively, 6 can be obtained from the reactions
      of 1-3 with an excess of the free IPr carbene ligand. The formation of 6 is
      sometimes accompanied by trace amounts of [Pt4(CO)4(IPr)3] (7). The reaction of 6
      with free IPr affords the closely related [Pt3(CO)3(IPr)3] (8) heteroleptic
      cluster by substitution of the unique terminal CO ligand with a third IPr ligand.
      The reactions of 1-3 with Ag(IMes)Cl [IMes = C3N2H2(C6H2Me3)2] proceed
      differently from those involving Ag(IPr)Cl. Indeed, the only product isolated
      after workup is the bimetallic tetranuclear cluster [Pt3(CO)3(IMes)3(AgCl)] (9).
      9 slowly reacts under a CO atmosphere, resulting in the pentanuclear
      [Pt5(CO)7(IMes)3] (10) complex. All of the new clusters 4-10 have been
      spectroscopically characterized and their molecular structures determined by X
      ray crystallography. 4 and 5 retain the original trigonal-prismatic structures of
      the parent anionic Chini clusters, which are capped by two [Ag(IPr)]+ moieties.
      Conversely, 6-9 are based on a Pt3 triangular core decorated by CO and N
      heterocyclic carbene ligands as well as Pt(CO) (in the case of 7) and AgCl (9)
      moieties. 10 displays an edge-bridged tetrahedral geometry.

PMID- 28489359
TI  - Liquid Beam Desorption Mass Spectrometry for the Investigation of Continuous Flow
      Reactions in Microfluidic Chips.
AB  - In this work, we present the combination of microfluidic chips and mass
      spectrometry employing laser-induced liquid beam ionization/desorption. The
      developed system was evaluated with respect to stable beam generation and laser
      parameters as well as solvent compatibility. The device was exemplarily applied
      to study a vinylogous Mannich reaction performed in continuous flow on chip. Fast
      processes can be observed with this technique which in the future could be
      beneficial for studying intermediates or contribute to the elucidation of
      reaction mechanisms.

PMID- 28489360
TI  - How Does Reference Site Selection Influence Interpretation of Omics Data?:
      Evaluating Liver Transcriptome Responses in Male Rainbow Darter (Etheostoma
      caeruleum) across an Urban Environment.
AB  - Studies quantifying the influence of reference site selection on transcriptomic
      profiles in aquatic organisms exposed to complex mixtures are lacking in the
      literature, despite the significant implications of such research for the
      interpretation of omics data sets. We measured hepatic transcriptomic responses
      in fish across an urban environment in the central Grand River watershed
      (Ontario, Canada). Adult male rainbow darter (RBD) (Etheostoma caeruleum) were
      collected from nine sites at varying distances from two major municipal
      wastewater treatment plants (MWWTPs) (Waterloo, Kitchener), including three
      upstream reference sites. The transcriptomic response in RBD was independently
      compared with that of fish from each of the three reference sites. Data collected
      in fish downstream of the Waterloo MWWTP (poorest effluent quality) suggested
      that ~15.5% of the transcriptome response was influenced by reference site
      selection. In contrast, at sites where the impact of MWWTPs was less-pronounced
      and fish showed less of a transcriptome response, reference site selection had a
      greater influence (i.e., ~56.9% of transcripts were different depending on the
      site used). This study highlights the importance of conducting transcriptomics
      studies that leverage more than one reference site, and it broadens our
      understanding of the molecular responses in fish in dynamic natural environments.

PMID- 28489361
TI  - Soluble Sugar Accumulation Can Influence Seed Size via AN3-YDA Gene Cascade.
AB  - In higher plants, seed size is central to many aspects in evolutionary fitness
      and is a crucial agricultural trait. In this study, Arabidopsis an3
      (angustifolia3) mutants present with increased seed size. Target-gene analysis
      revealed that YDA, which encodes a mitogen-activated protein kinase kinase
      kinase, is a target gene of AN3. Indeed, the loss of YDA function decreases seed
      size. Furthermore, AN3 and YDA mutations both disrupt normal sucrose and glucose
      contents and cause altered seed size in an3 or yda mutants. With these results,
      we provide a molecular model in which soluble sugar accumulation might affect
      seed size regulation via the AN3-YDA gene cascade. Our findings guide the
      synthesis of a model that predicts the integration of soluble sugar accumulation
      at AN3 to control the establishment of seed size.

PMID- 28489362
TI  - Atropisomerism and Conformational Equilibria: Impact on PI3Kdelta Inhibition of 2
      ((6-Amino-9H-purin-9-yl)methyl)-5-methyl-3-(o-tolyl)quinazolin-4(3H)-one
      (IC87114) and Its Conformationally Restricted Analogs.
AB  - IC87114 [compound 1, (2-((6-amino-9H-purin-9-yl)methyl)-5-methyl-3-(o
      tolyl)quinazolin-4(3H)-one)] is a potent PI3K inhibitor selective for the delta
      isoform. As predicted by molecular modeling calculations, rotation around the
      bond connecting the quinazolin-4(3H)-one nucleus to the o-tolyl is sterically
      hampered, which leads to separable conformers with axial chirality (i.e.,
      atropisomers). After verifying that the aS and aR isomers of compound 1 do not
      interconvert in solution, we investigated how biological activity is influenced
      by axial chirality and conformational equilibrium. The aS and aR atropisomers of
      1 were equally active in the PI3Kdelta assay. Conversely, the introduction of a
      methyl group at the methylene hinge connecting the 6-amino-9H-purin-9-yl pendant
      to the quinazolin-4(3H)-one nucleus of both aS and aR isomers of 1 had a critical
      effect on the inhibitory activity, indicating that modulation of the
      conformational space accessible for the two bonds departing from the central
      methylene considerably affects the binding of compound 1 analogues to PI3Kdelta
      enzyme.

PMID- 28489363
TI  - Correction to "Air- and Light-Stable P4 and As4 within an Anion-Coordination
      Based Tetrahedral Cage".

PMID- 28489364
TI  - Fate of d-Fagomine after Oral Administration to Rats.
AB  - d-Fagomine is an iminosugar found in buckwheat that is capable of inhibiting the
      adhesion of potentially pathogenic bacteria to epithelial mucosa and reducing the
      postprandial blood glucose concentration. This paper evaluates the excretion and
      metabolism of orally administered d-fagomine in rats and compares outcomes with
      the fate of 1-deoxynojirimycin. d-Fagomine and 1-deoxynojirimycin show similar
      absorption and excretion kinetics. d-Fagomine is partly absorbed (41-84%, dose of
      2 mg/kg of body weight) and excreted in urine within 8 h, while the non-absorbed
      fraction is cleared in feces within 24 h. d-Fagomine is partially methylated
      (about 10% in urine and 3% in feces). The concentration of d-fagomine in urine
      from 1 to 6 h after administration is higher than 10 mg/L, the concentration that
      inhibits adhesion of Escherichia coli. Orally administered d-fagomine is
      partially absorbed and then rapidly excreted in urine, where it reaches a
      concentration that may be protective against urinary tract infections.

PMID- 28489365
TI  - Between Descriptors and Properties: Understanding the Ligand Efficiency Trends
      for G Protein-Coupled Receptor and Kinase Structure-Activity Data Sets.
AB  - The chemical meaning of the ligand efficiency (LE) metrics is explained in this
      paper using a large G protein-coupled receptor (GPCR) and kinase structure
      activity (IC50, Ki) data set. Although there is a controversy in the literature
      regarding both the mathematical validity and the performance of LE, it is in
      common use as an early estimator for drug optimization. Apparently, the numerous
      con arguments are not convincing enough. We show here for the first time that the
      main misunderstanding of the chemical meaning of LE is its interpretation as a
      molecular descriptor connected with a single molecule. Instead, LE should be
      interpreted as a statistical property. We show that the LE, which is designed as
      a regression of a binding property on the heavy atom count (HAC), is correlated
      to the reciprocal of the molecular weight because of Avogadro statistics. This
      indicates that the hyperbolic model of LE is basically a consequence of a
      nonbinding effect, an increase in the number of ligands that are available to a
      receptor for smaller molecules, and not a real increase in the binding potency
      for a single HAC as interpreted in the literature. Accordingly, we need to
      revisit and carefully reevaluate LE-based molecular comparisons.

PMID- 28489366
TI  - Correction to Reparameterization of Solute-Solute Interactions for Amino Acid
      Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.

PMID- 28489367
TI  - Franck-Condon Models for Simulating the Band Shape of Electronic Absorption
      Spectra.
AB  - Band shape is an essential ingredient in the simulation of electronic absorption
      spectra. The excitation of multiple series of vibrational levels during an
      electronic excitation is a main contributor to band shapes. Here we present two
      simple models based on the Franck-Condon displaced-harmonic-oscillator model. The
      models are both derived from the time-dependent formulation of electronic
      spectroscopy. They assume that the transition dipoles do not depend on geometry
      and that the potential energy surfaces are locally quadratic; one model is second
      order in time and is called LQ2, and the other is third order in time and is
      called LQ3. These models are suitable for simulating the unresolved vibronic band
      shapes of electronic spectra that involve many vibrational modes. The models are
      straightforward and can be easily applied to simulate absorption spectra that are
      composed of many electronic transitions. As compared to carrying out molecular
      dynamics simulations, they require relatively few electronic structure
      calculations, and the additional cost for constructing the spectra is negligible.
      Therefore, the models are suitable for simulating the spectra of complex systems
      such as transition-metal complexes.

PMID- 28489369
TI  - QM/MM Investigation of Substrate and Product Specificities of Suv4-20h2: How Does
      This Enzyme Generate Dimethylated H4K20 from Monomethylated Substrate?
AB  - Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine
      residues on histone proteins in the regulation of chromatin structure and gene
      expression. In contrast to many other PKMTs for which unmodified lysine is the
      methylation target, the enzymes in the Suv4-20 family are able to generate
      dimethylated product (H4K20me2) based exclusively on the monomethylated H4K20
      substrate (H4K20me1). The origin of such substrate/product specificity is still
      not clear. Here, molecular dynamics (MD) and free energy (potential of mean
      force) simulations are undertaken using quantum mechanical/molecular mechanical
      (QM/MM) potentials to understand the substrate/product specificities of Suv4
      20h2, a member of the Suv4-20 family. The free energy barriers for mono-, di-,
      and trimethylation in Suv4-20h2 obtained from the simulations are found to be
      well correlated with the specificities observed experimentally with the allowed
      dimethylation based on the H4K20me1 substrate and prohibited monomethylation and
      trimethylation based on H4K20 and H4K20me2, respectively. It is demonstrated that
      the reason for the relatively efficient dimethylation is an effective transition
      state (TS) stabilization through strengthening the CH...O interactions as well as
      the presence of a cation-pi interaction at the transition state. The simulations
      also show that the failures of Suv4-20h2 to catalyze monomethylation and
      trimethylation are due, respectively, to a less effective TS stabilization and
      inability of the reactant complex containing H4K20me2 to adopt a reactive (near
      attack) configuration for methyl transfer. The results suggest that care must be
      exercised in the prediction of the substrate specificity based only on the
      existence of near attack configurations in substrate complexes.

PMID- 28489368
TI  - On-the-Fly ab Initio Semiclassical Calculation of Glycine Vibrational Spectrum.
AB  - We present an on-the-fly ab initio semiclassical study of vibrational energy
      levels of glycine, calculated by Fourier transform of the wavepacket correlation
      function. It is based on a multiple coherent states approach integrated with
      monodromy matrix regularization for chaotic dynamics. All four lowest-energy
      glycine conformers are investigated by means of single-trajectory semiclassical
      spectra obtained upon classical evolution of on-the-fly trajectories with
      harmonic zero-point energy. For the most stable conformer I, direct dynamics
      trajectories are also run for each vibrational mode with energy equal to the
      first harmonic excitation. An analysis of trajectories evolved up to 50 000
      atomic time units demonstrates that, in this time span, conformers II and III can
      be considered as isolated species, while conformers I and IV show a pretty facile
      interconversion. Therefore, previous perturbative studies based on the assumption
      of isolated conformers are often reliable but might be not completely appropriate
      in the case of conformer IV and conformer I for which interconversion occurs
      promptly.

PMID- 28489370
TI  - Improved Polarizable Dipole-Dipole Interaction Model for Hydrogen Bonding,
      Stacking, T-Shaped, and X-H...pi Interactions.
AB  - The polarizable dipole-dipole interaction model was formulated in our laboratory
      to rapidly simulate hydrogen bonding in biosystems. In this paper, this model is
      improved and further parametrized for stacking, T-shaped, and X-H...pi
      interactions by adding the orbital overlap term and fitting to 19 CCSD(T)/CBS
      interaction energy curves of training dimers. The performance of our model is
      assessed through its application to more than 100 complexes, including hydrogen
      bonded, stacked, T-shaped, and X-H...pi complexes. For 124 relatively small
      testing complexes, our model reproduces benchmark equilibrium intermolecular
      distances with a root-mean-square deviation (RMSD) of 0.08 A, and it reproduces
      benchmark interaction energies with a 0.64 kcal/mol RMSD. For 14 large
      noncovalent complexes, our model reproduces benchmark equilibrium intermolecular
      distances with a RMSD of 0.05 A, and it reproduces benchmark interaction energies
      with a 0.80 kcal/mol RMSD. Extensive comparisons are made to interaction energies
      calculated via the M06-2X and M06-2X-D3 methods, via the well-known
      nonpolarizable AMBER99 force field method, via the popular polarizable AMOEBA
      force field method, and via semiempirical quantum mechanical (SQM) methods. Our
      statistical evaluations show that our model outperforms the AMBER99, AMOEBA, and
      SQM methods and is as accurate as the M06-2X and M06-2X-D3 methods. In summary,
      the model developed in this work is reasonable, and the newly introduced orbital
      overlap term is effective in the accurate modeling of the noncovalent
      interactions. Our testing results also indicate that the polarization interaction
      term is important in the evaluation of hydrogen bonding, whereas the orbital
      overlap is important in examining short hydrogen bonding, T-shaped, and X-H...pi
      interactions. Our model may serve as a new tool for modeling biological systems
      where hydrogen bonding, stacking, T-shaped, and X-H...pi interactions are of
      general importance.

PMID- 28489371
TI  - Nickel-Catalyzed Cross-Coupling of Vinyl Dioxanones to Form Enantiomerically
      Enriched Cyclopropanes.
AB  - Under the conditions of nickel(0) catalysis, enantiomerically enriched vinyl
      dioxanones engage boroxines or B2(pin)2 in stereospecific cross-coupling to form
      diverse tetrasubstituted cyclopropanes bearing all-carbon quaternary
      stereocenters. The collective data corroborate a mechanism involving nickel(0)
      mediated benzylic oxidative addition with inversion of stereochemistry followed
      by reversible olefin insertion to form a (cyclopropylcarbinyl)nickel complex,
      which upon reductive elimination releases the cyclopropane.

PMID- 28489372
TI  - Psi4 1.1: An Open-Source Electronic Structure Program Emphasizing Automation,
      Advanced Libraries, and Interoperability.
AB  - Psi4 is an ab initio electronic structure program providing methods such as
      Hartree-Fock, density functional theory, configuration interaction, and coupled
      cluster theory. The 1.1 release represents a major update meant to automate
      complex tasks, such as geometry optimization using complete-basis-set
      extrapolation or focal-point methods. Conversion of the top-level code to a
      Python module means that Psi4 can now be used in complex workflows alongside
      other Python tools. Several new features have been added with the aid of
      libraries providing easy access to techniques such as density fitting, Cholesky
      decomposition, and Laplace denominators. The build system has been completely
      rewritten to simplify interoperability with independent, reusable software
      components for quantum chemistry. Finally, a wide range of new theoretical
      methods and analyses have been added to the code base, including functional-group
      and open-shell symmetry adapted perturbation theory, density-fitted coupled
      cluster with frozen natural orbitals, orbital-optimized perturbation and coupled
      cluster methods (e.g., OO-MP2 and OO-LCCD), density-fitted multiconfigurational
      self-consistent field, density cumulant functional theory, algebraic-diagrammatic
      construction excited states, improvements to the geometry optimizer, and the
      "X2C" approach to relativistic corrections, among many other improvements.

PMID- 28489373
TI  - Scalemic Caged Xanthones Isolated from the Stem Bark Extract of Garcinia
      propinqua.
AB  - Seven new caged xanthones, doitunggarcinones E-K (1-7), all as scalemic mixtures
      and 10 known compounds (8-17), were isolated from the stem bark extract of
      Garcinia propinqua. The structures were elucidated on the basis of spectroscopic
      methods. The separation of the enantiomers of 1-6 was achieved by semipreparative
      chiral HPLC. The absolute configuration of compound (+)-1 was determined by
      single-crystal X-ray crystallographic analysis using Cu Kalpha radiation. The
      absolute configurations of the other related compounds were determined from
      comparisons of their ECD spectra with that of compound (+)-1. Compounds (-)-6 and
      7 showed cytotoxicity against a colon cancer cell line with IC50 values of 14.23
      and 23.95 MUM, respectively.

PMID- 28489374
TI  - Theoretical Study of the Pair-Correlated F + CHD3(v = 0,nu1 = 1) Reaction: Effect
      of CH Stretching Vibrational Excitation.
AB  - The F + CHD3(v) reaction is a benchmark system in polyatomic reactions.
      Theoretical/experimental comparisons have been reported in recent years that
      present some controversies, specifically the role of the reactant CH stretching
      vibrational excitation, CHD3(nu1 = 1), on the reactivity of both isotope
      channels, DF(v) + CHD2(v') and HF(v) + CD3(v'). However, in many cases, these
      comparisons are not made on an equal footing. Previous theoretical studies were
      concerned with overall reactivity of each isotope channel, while fine velocity
      map imaging experiments provided results in a product pair-correlated manner. In
      order to shed some light on these controversies, we perform here a pair
      correlated theory/experiment comparison for the title reaction, using quasi
      classical trajectory calculations on a full dimensional potential energy surface.
      When these calculations are analyzed in a quantum spirit, i.e., by discarding
      those trajectories whose results do not meet quantum-mechanical requirements and
      aiming to reproduce stringent experimental constraints, some of the discrepancies
      on overall reactivity and the effect of the CH vibrational excitation are now
      resolved. Agreement with the available experimental studies, though still
      qualitative in some aspects, has noticeably improved.

PMID- 28489375
TI  - Involvement of the Glucocorticoid Receptor in Pro-inflammatory Transcription
      Factor Inhibition by Daucane Esters from Laserpitium zernyi.
AB  - Species of the genus Laserpitium have been used traditionally to treat
      inflammation and infection. From the herb of Laserpitium zernyi, six new
      compounds were isolated and their structures elucidated (using IR, NMR, HRMS
      data) as derivatives of 8-daucene-2,4,10-triol (1, 2, and 4), 7-daucene-2,4,10
      triol (3), a lapiferin derivative featuring a C-2 ester moiety (5), and a daucane
      featuring an exomethylene group at C-8 (6). Also isolated were the rare daucanes
      vaginatin (7) and laserpitin (8). In a search for selective glucocorticoid
      receptor (GR) modulators, the compounds were tested for their capacity to inhibit
      NF-kappaB and AP-1 pro-inflammatory factors and for a potential competitive
      effect on a dexamethasone (Dex)-induced GR-driven glucocorticoid response element
      (GRE) reporter gene. The new 2beta-angeloyloxy-10alpha-acetoxy-8-daucene-2,4,10
      triol (2) significantly inhibited transactivation of both NF-kappaB and AP-1,
      while vaginatin (7) was the most active of the compounds tested in blocking AP-1.
      Both compounds competitively repressed Dex-induced GRE-driven promoter
      activities, indicative of a potential role for GR. In addition, a decreased
      potential to inhibit NF-kappaB was apparent in GR knockout A549 cells. In line
      with the transcriptional assays, compounds 2 and 7 also significantly lowered CCL
      2 chemokine production, albeit to a lesser extent than Dex. The results suggest
      that daucanes may be interesting candidates in the search for compounds with GR
      modulating activities.

PMID- 28489376
TI  - Interplay Between pi-Stacking and Hydrogen Bonding in the Self-Association of
      Different Isomers of Naphthalenedicarboxylic Acid.
AB  - Using proton and carbon chemical shifts, we investigated the self-association of
      three isomers of naphthalenedicarboxylic acid, a model for the aggregation of
      asphaltenes. Experimental proton chemical shifts of each isomer were measured as
      a function of concentration in an aprotic solvent. Several potential structures
      of the monomer and dimer of each naphthalenedicarboxylic acid were considered,
      and calculated proton chemical shifts for the potential monomer and dimer
      structures were compared to the experimental chemical shifts to find the weighted
      average structure that best fit the experimental shifts. Calculated carbon
      chemical shifts were also compared to experimental values. The chemical shift
      comparison and calculated energies indicate that pi-stacked dimers are not likely
      to contribute significantly to the dimer structure of any of the three
      naphthalenedicarboxylic acid isomers studied.

PMID- 28489377
TI  - Svetamycins A-G, Unusual Piperazic Acid-Containing Peptides from Streptomyces sp.
AB  - Seven new halogenated peptides termed svetamycins A-G (1-7) have been isolated
      from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are
      cyclic depsipeptides, whereas svetamycin E is a linear analogue of svetamycin C.
      Their structures were determined using extensive spectroscopic analysis, and
      their stereochemical configuration was established by a combination of NMR data,
      quantum mechanical calculations, and chemical derivatizations. Svetamycins are
      characterized by the presence of a hydroxyl acetic acid and five amino acids
      including a rare 4,5-dihydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, a
      gamma-halogenated piperazic acid, and a novel delta-methylated piperazic acid in
      svetamycins B-C, E, and G. Moreover, isotope-labeled substrate feeding
      experiments demonstrated ornithine as the precursor of piperazic acid and that
      methylation at the delta position of the piperazyl scaffold is S-adenosyl-l
      methionine (SAM)-dependent. Svetamycin G, the most potent antimicrobial of this
      suite of compounds, inhibited the growth of Mycobacterium smegmatis with an MIC80
      value of 2 MUg/mL.

PMID- 28489378
TI  - Radical Chain Reduction of CCl4 Initiated by Illumination of SPEEK Solutions.
AB  - Efficient reduction of CCl4 took place upon exposure to 350-nm photons of aqueous
      solutions containing sulfonated poly(ether etherketone) (SPEEK) as a sensitizer
      and either poly(vinyl alcohol) (PVA) or HCO2H/HCO2- buffer. The photoreaction
      formed chloride ions whose concentration increased linearly with time in
      solutions free of O2, whereas slower reductions occurred in the presence of air.
      Utilization of formate buffer as the H-atom donor yielded photoreactions at least
      10 times faster than those in the presence of PVA and generated CHCl3 as another
      reaction product. The quantum yield of chloride ion formation, o(Cl-), was found
      to be a function of both the SPEEK concentration and concentration of formate
      buffer. Whereas the quantum efficiency increased steadily with decreasing
      solution acidity, a drastic surge in the reaction rate occurred in neutral
      solutions. o(Cl-) first increased rapidly to a maximum value exceeding 1 at pH
      7.3 and then decreased thereafter. The dependence of r(Cl-) on (I0)1/2, where I0
      is the light intensity, and the occurrence of postirradiation formation of Cl-
      through the reduction of CCl4 in the dark are further evidence that the
      photoreaction proceeded by a chain process. Several of the kinetic features were
      rationalized by means of a mechanism involving the alpha-hydroxy radicals of
      SPEEK and *CCl3 as chain carriers.

PMID- 28489379
TI  - Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for beta-Arrestin
      Biased D2R Agonists.
AB  - By means of a formal structural hybridization of the antipsychotic drug
      aripiprazole and the heterocyclic catecholamine surrogates present in the beta2
      adrenoceptor agonists procaterol and BI-167107 (4), we designed and synthesized a
      collection of novel hydroxy-substituted heteroarylpiperazines and
      heteroarylhomopiperazines with high dopamine D2 receptor (D2R) affinity. In
      contrast to the weak agonistic behavior of aripiprazole, these ligands are
      capable of effectively mimicking those interactions of dopamine and the D2R that
      are crucial for an active state, leading to the recruitment of beta-arrestin-2.
      Interestingly, some ligands show considerably lower intrinsic activity in guanine
      nucleotide exchange experiments at D2R and consequently represent biased agonists
      favoring beta-arrestin-2 recruitment over canonical G protein activation. The
      ligands' agonistic properties are substantially driven by the presence of an
      endocyclic H-bond donor.

PMID- 28489380
TI  - Facile Approach to Perylenemonoimide with Short Side Chains for Nonfullerene
      Solar Cells.
AB  - Electron acceptors based on perylene monoimide (PMI) are rare due to the
      synthetic challenge. Herein, starting from commercially available perylene
      dianhydride, brominated perylene monoimide (PMI-Br) with short side chains and
      good solubility was efficiently synthesized in a high overall yield of 71%. With
      PMI-Br as the intermediate, acceptor-donor-acceptor type electron acceptors with
      low-lying LUMO energy levels and strong visible absorption were successfully
      obtained. The nonfullerene bulk heterojunction solar cells based on these
      acceptors were fabricated with the highest PCE of 1.3%.

PMID- 28489381
TI  - Molecular Mechanism of the Reaction Specificity in Threonine Synthase: Importance
      of the Substrate Conformations.
AB  - Threonine synthase (ThrS) catalyzes the final chemical reaction of l-threonine
      biosynthesis from its precursor, O-phospho-l-homoserine. As the phosphate ion
      generated in its former half reaction assists its latter reaction, ThrS is
      recognized as one of the best examples of product-assisted catalysis. In our
      previous QM/MM study, the chemical reactions for the latter half reactions, which
      are critical for the product-assisted catalysis, were revealed. However, accurate
      free energy changes caused by the conformational ensembles and entrance of water
      molecules into the active site are unknown. In the present study, by performing
      long-time scale MD simulations, the free energy changes by the divalent anions
      (phosphate or sulfate ions) and conformational states of the intermediate states
      were theoretically investigated. We found that the calculated free energy double
      differences are in good agreement with the experimental results. We also revealed
      that the phosphate ion contributes to forming hydrogen bonds that are suitable
      for the main reaction progress. This means that the conformation of the active
      site amino acid residues and the substrate, and hence, the tunable catalysis, are
      controlled by the product phosphate ion, and this clearly demonstrates a
      molecular mechanism of the product-assisted catalysis in ThrS.

PMID- 28489382
TI  - Antimicrobial Spirotetronate Metabolites from Marine-Derived Micromonospora
      harpali SCSIO GJ089.
AB  - Two new spirotetronate aglycones, 22-dehydroxymethyl-kijanolide (1) and 8-hydroxy
      22-dehydroxymethyl-kijanolide (2), along with seven new spirotetronate
      glycosides, microsporanates A-F (3-8) and tetrocarcin P (9), together with three
      known tetrocarcins [tetrocarcins A (10), B (11), and AC6H (12)], were isolated
      from fermentation broths of the marine-derived Micromonospora harpali SCSIO
      GJ089. The structures of 1-9 were elucidated on the basis of 1D and 2D NMR and MS
      spectroscopic data. Compounds 3-8 feature an alpha,beta-unsaturated carbonyl
      moiety within their spirotetronate skeletons. Moreover, compounds 3-12 displayed
      strong to moderate antibacterial activities against Gram positive bacteria
      Bacillus thuringiensis BT01 and B. subtilis BS01 with MIC values ranging from
      0.016 to 8.0 MUg/mL.

PMID- 28489383
TI  - Confined Electroconvective and Flexoelectric Instabilities Deep in the
      Freedericksz State of Nematic CB7CB.
AB  - We report wormlike flexoelectric structures evolving deep in the Freedericksz
      state of a nematic layer of the liquid crystal cyanobiphenyl-(CH2)7
      cyanobiphenyl. They form in the predominantly splay-bend thin boundary layers and
      are built up of solitary flexoelectric domains of the Bobylev-Pikin type. Their
      formation is possibly triggered by the gradient flexoelectric surface instability
      that remains optically discernible up to unusually high frequencies. The
      threshold voltage at which the worms form scales as square root of the frequency;
      in their extended state, worms often appear as labyrinthine structures on a
      section of loops that separate regions of opposite director deviation. Such
      asymmetric loops are also derived through pincement-like dissociation of ring
      shaped walls. Formation of isolated domains of bulk electroconvection precedes
      the onset of surface instabilities. In essence, far above the Freedericksz
      threshold, the twisted nematic layer behaves as a combination of two orthogonally
      oriented planar half-layers destabilized by localized flexoelectric distortion.

PMID- 28489384
TI  - Rethinking Dithiothreitol-Based Particulate Matter Oxidative Potential: Measuring
      Dithiothreitol Consumption versus Reactive Oxygen Species Generation.
AB  - We measured the rate of generation of reactive oxygen species (ROS) [hydroxyl
      radicals (*OH) and hydrogen peroxide (H2O2)] catalyzed by ambient particulate
      matter (PM) in the dithiothreitol (DTT) assay. To understand the mechanism of ROS
      generation, we tested several redox-active substances, such as 9,10
      phenanthrenequinone (PQ), 5-hydroxy-1,4-naphthoquinone (5H-1,4NQ), 1,2
      naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), copper(II), manganese(II),
      and iron (II and III). Both pure compounds and their mixtures show different
      patterns in DTT oxidation versus ROS generation. The quinones, known to oxidize
      DTT in the efficiency order of PQ > 5H-1,4NQ > 1,2-NQ > 1,4-NQ, show a different
      efficiency order (5H-1,4NQ > 1,2-NQ ~ PQ > 1,4-NQ) in the ROS generation. Cu(II),
      a dominant metal in DTT oxidation, contributes almost negligibly to the ROS
      generation. Fe is mostly inactive in DTT oxidation, but shows synergistic effect
      in *OH formation in the presence of other quinones (mixture/sum > 1.5). Ten
      ambient PM samples collected from an urban site were analyzed, and although DTT
      oxidation was significantly correlated with H2O2 generation (Pearson's r = 0.91),
      no correlation was observed between DTT oxidation and *OH formation. Our results
      show that measuring both DTT consumption and ROS generation in the DTT assay is
      important to incorporate the synergistic contribution from different aerosol
      components and to provide a more inclusive picture of the ROS activity of ambient
      PM.

PMID- 28489385
TI  - Nanoscaled Amorphous TiO2 Hollow Spheres: TiCl4 Liquid Droplet-Based Hydrolysis
      Fabrication and Strong Hollow Structure-Enhanced Surface-Enhanced Raman
      Scattering Effects.
AB  - A very simple route is developed for fast fabrication of nanosized amorphous
      titanium dioxide (TiO2) hollow spheres (THPs) just via dropping the pure four
      titanium chloride (TiCl4) liquid droplets into deionized water at around room
      temperature. The THPs, at around 80 nm in mean diameter, can be formed within a
      few seconds after dropping TiCl4 droplets into water. The shell layers of the
      obtained THPs are amorphous and porous in structure with a porosity of 58-80% and
      show a linear increase in thickness with the size of THPs. Further experiments
      have revealed that the reaction temperature, initial pH value, and size of the
      TiCl4 droplet are crucial to the formation, size, productivity, and
      microstructure of the THPs. A model is proposed on the basis of the fragmentation
      of liquid droplets, hydrolysis-induced formation, and inward growth of TiO2 shell
      layers, which can well describe the formation of the THPs. Importantly, such
      amorphous nanoscaled THPs have exhibited some strong hollow structure-enhanced
      performances. Typically, the THP-built film shows the highest reflectivity in the
      visible region compared to the other structured TiO2 films. Especially, if it
      supports the film of the Au nanoparticle, the surface-enhanced Raman scattering
      effect is significantly enhanced by more than 1 order of magnitude. This work
      provides not only a simple and quick fabrication method for the THPs but also a
      new member for their family.

PMID- 28489386
TI  - One-Step Synthesis of Hydrophobic Multicompartment Organosilica Microspheres with
      Highly Interconnected Macro-mesopores for the Stabilization of Liquid Marbles
      with Excellent Catalysis.
AB  - The combination of an emulsion template with polymerization is a very convenient
      approach to the one-step realization of both simple control porous structures via
      a change in emulsion formulation and easy functionalization via the concomitant
      choice of an on-demand monomer. A major challenge of this approach is the
      inherent instability of the oil/water interface in emulsions, especially the
      occurrence of chemical reactions in oil or aqueous phases. This study reports the
      pioneering preparation of highly interconnected macro-mesopores and
      multicompartment (HIMC) vinyl organosilica microspheres with hydrophobicity by
      the one-step formation of W/O/W emulsions acting as a template. The emulsion
      system consists of acidified deionized water, a stabilizer, and
      vinyltriethoxysilane (VTEO) in which VTEO can be used to produce an organosilica
      skeleton of the resultant microsphere by a sol-gel process. The study
      demonstrated that the marvelous stability of W/O/W emulsions aids the formation
      of multicompartment organosilica microspheres with highly interconnected macro
      mesopores by emulsion droplets rather than single-compartment (SC) microspheres.
      Meanwhile, the internal porous structure and surface morphology of as-prepared
      organosilica microspheres could be largely tuned by a simple variation of the pH
      value, the volume fraction of the water phase, and the stabilizer concentration
      in the initiating multiemulsions. Benefiting from such a well-orchestrated
      structure and the existence of numerous vinyl groups on the surface, HIMC
      organosilica microspheres exhibit very high hydrophobicity (with a water contact
      angle larger than 160 degrees ), which allows them to stabilize liquid marbles
      with excellent stability and high mechanical robustness. Because of its strong
      catalyst, Ag nanoparticles within HIMC organosilica microspheres enable Ag/HIMC
      vinyl organosilica microsphere-based liquid marbles to be an efficient catalytic
      microreactor, realizing the complete degradation of MB to leuco methylene blue by
      NaBH4 in 10 min. The result of this work could provide some guidance for the
      easy, low-cost, benign preparation of HIMC microspheres having the potential to
      be excellent supporter of metal nanoparticles or other functionalized compounds
      for applications in sensing, optoelectronics, and catalysis.

PMID- 28489387
TI  - Reactive Hypersaline Route: One-Pot Synthesis of Porous Photoactive
      Nanocomposites.
AB  - Herein, porous photoactive nanocomposites are prepared by a simple one-pot
      synthesis approach using a salt and aqueous media. Within this reactive
      hypersaline route, the salt not only serves in the structuring of the composite
      but also becomes an integral active part of it. Here, the addition of sodium
      thiocyanate to a titania precursor guides, on the one hand, the formation of
      needle-shaped nanoparticles and, on the other hand, forms yellow compound
      isoperthiocyanic acid, which is homogeneously incorporated into the porous
      nanocomposite. Compared to a pure titania reference, this material reveals a 7
      fold-increased photodegradation rate of Rhodamine B as a model compound. This
      reveals the reactive hypersaline route to be a promising and facile synthesis
      route toward photoactive porous materials.

PMID- 28489388
TI  - Ultrathin and Highly Passivating Silica Shells for Luminescent and Water-Soluble
      CdSe/CdS Nanorods.
AB  - Microemulsion (water-in-oil) methods enable the encapsulation of individual
      nanoparticles into SiO2 spheres. The major drawbacks of this method, when applied
      for silica encapsulation of anisotropic nanorods (NRs), are spatially unequal
      silica growth and long reaction times (24 h at least). In this work, various
      tetraalkoxysilanes [tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate
      (TEOS), and tetrapropyl orthosilicate (TPOS)] with different alkyl-chain lengths
      were used as silica precursors in attempt to tune the silanization behavior of
      CdSe/CdS NRs in a microemulsion system. We find enhanced spatial homogeneity of
      silica growth with decreasing alkyl-chain length of the tetraalkoxysilanes. In
      particular, by use of TMOS as the precursor, NRs can be fully encapsulated in a
      continuous thin (<=5 nm) silica shell within only 1 h reaction time.
      Surprisingly, the thin silica shell showed a superior shielding ability to acidic
      environment, even compared to the 30 nm thick shell prepared by use of TEOS. Our
      investigations suggest that the lower steric hindrance of TMOS compared to TEOS
      or TPOS strongly promotes homogeneous growth of the silica shells, while its
      increased hydrolysis rate decreases the porosity of these shells.

PMID- 28489389
TI  - Stabilization of Foam Lamella Using Novel Surface-Grafted Nanocellulose-Based
      Nanofluids.
AB  - To solve the potential risk of present oilfield chemistries to subterranean
      environment, our group contributes to the development of "green" petroleum
      production processes. This proof-of-concept research studied the well-defined
      nanocellulose-based nanofluids, i.e., original (NC), AMPS grafted (NC-KY), and
      AMPS and hydrophobic chains grafted (NC-KYSS), in stabilizing foam lamella for
      potential use in enhanced oil recovery (EOR). The data showed that the
      collaboration of the surface-functional nanocellulose considerately improved the
      foam stability particularly in the presence of hydrocarbons due to the thickened
      foam film coupled with the molecular interactions at interior lamella. Since the
      grafted AMPS and alkyl chains, NC-KYSS noticeably enhanced foam quality compared
      against NC and NC-KY. With the increase in gas pressure, the lamella stabilizing
      effect of NC-KYSS became increasingly significant. The coflowing behaviors of
      foam with oleic phase in porous media were examined in a five-spot visualization
      micromodel (15 cm * 15 cm * 1 cm) and identified using a digital analysis method.
      The defoaming/destabilizing effect of hydrocarbons was fairly notable in porous
      media, causing the foam to finger through the formed "oil bank". However, a tough
      displacement front was constructed when the surfactant synergized with NC-KYSS
      due to the stabilized foam lamella and 12% of incremental oil recovery was
      produced.

PMID- 28489390
TI  - Synthesis of Ni9S8/MoS2 heterocatalyst for Enhanced Hydrogen Evolution Reaction.
AB  - We demonstrate a heterostructure Ni9S8/MoS2 hybrid with tight interface
      synthesized via an improved hydrothermal method. As compared to pure MoS2, the
      increased surface area and the shorten charge transport pathway in the layered
      hybrid significantly promote the photocatalytic efficiency for hydrogen evolution
      reaction (HER). In particularly, the optimized Ni9S8/MoS2 hybrid with 20 wt %
      Ni9S8 exhibits the highest photocatalytic activity with HER value of 406 MUmolg
      1h-1, which is enhanced by 70% compared to that of pure MoS2 nanosheets (285.0
      MUmolg-1h-1). Moreover, the value is 4 times more than the commercial MoS2 (92.0
      MUmolg-1h-1), indicating the high potential of the hybrid in the catalytic
      fields.

PMID- 28489391
TI  - Helium Nanobubbles Enhance Superelasticity and Retard Shear Localization in Small
      Volume Shape Memory Alloy.
AB  - The intriguing phenomenon of metal superelasticity relies on stress-induced
      martensitic transformation (SIMT), which is well-known to be governed by
      developing cooperative strain accommodation at multiple length scales. It is
      therefore scientifically interesting to see what happens when this natural length
      scale hierarchy is disrupted. One method is producing pillars that confine the
      sample volume to micrometer length scale. Here we apply yet another intervention,
      helium nanobubbles injection, which produces porosity on the order of several
      nanometers. While the pillar confinement suppresses superelasticity, we found the
      dispersion of 5-10 nm helium nanobubbles do the opposite of promoting
      superelasticity in a Ni53.5Fe19.5Ga27 shape memory alloy. The role of helium
      nanobubbles in modulating the competition between ordinary dislocation slip
      plasticity and SIMT is discussed.

PMID- 28489392
TI  - Theoretical Study on the Negative Thermal Expansion Perovskite LaCu3Fe4O12:
      Pressure-Triggered Transition of Magnetism, Charge, and Spin State.
AB  - The A-site ordered negative thermal expansion material LaCu3Fe4O12 (LaCFO) was
      comprehensively investigated by using first-principles calculations. A pressure
      triggered crystal structural phase transition from space group Im3 (No. 204) to
      Pn3 (No. 201) and magnetic transformation from a G-type antiferromagnetic (G_AFM)
      ground state to ferrimagnetic (FerriM) coupling were observed in LaCFO via
      gradual compression of the equilibrium volume. Correspondingly, the Fe-Cu
      intersite charge transfer from Fe to Cu 3dxy orbital, expressed as 4Fe3+ + 3Cu3+ 
      > 4Fe3.75+ + 3Cu2+, was simulated along with the magnetic phase transformation
      from the G_AFM configuration to the FerriM state. Intriguingly, the Fe charge
      disproportionation, formulated as 8Fe3.75+ -> 5Fe3+ + 3Fe5+, appeared and was
      attributed to the strong hybridization between Fe 3d and O 2p orbitals in the
      FerriM state when the volumes were substantially compressed up to less than or
      equal to 80%V. Meanwhile, the external hydrostatic pressure also leads to a spin
      flip from a high-spin Fe3+ antiferromagnetically arranged LaCu3+3Fe3+4O12 Mott
      insulator at low pressure and goes through a FerriM LaCu2+3Fe3.75+4O12 half-metal
      to a low-spin FerriM coupled LaCu2+3Fe3+5/2Fe5+3/2O12 metal at high pressure.
      Therefore, the crossover from high spin to low spin is responsible for the charge
      disproportionation in LaCFO. Essentially, the charge transfer and spin flip
      originate from the discontinuous changes of metal-oxygen bond lengths and angles
      in the compressed atomic structure. Finally, the negative thermal expansion
      behavior and mechanism of LaCFO were theoretically examined and clearly revealed.

PMID- 28489393
TI  - Ag2O/TiO2 Nanocomposite Heterostructure as a Dual Functional Semiconducting
      Substrate for SERS/SEIRAS Application.
AB  - Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared
      absorption spectroscopy (SEIRAS) are complementary and powerful techniques for
      molecular characterization and detection. However, studies on substrates that can
      enhance both Raman and IR singles are extremely scanty. Here, we reported a
      hybrid semiconductor material (Ag2O/TiO2) coupled with a portable solid support
      served as a dual functional platform for both SERS and SEIRAS applications. A
      facile two-step deposition method was used to synthesize Ag2O/TiO2 nanocomposite
      on a flexible polymeric membrane without bringing any external chemical capping
      agent and background signal. The presence of Ag2O was proposed to enrich the
      photogenerated electrons onto TiO2 surface and facilitate the photon-induced
      charge transfer (PICT) between TiO2 and adsorbate. The heterostructure of
      Ag2O/TiO2 could bring additional enhancement. The enhancement factor from such
      hybrid semiconducting substrate was at least one or two orders of magnitude over
      traditional semiconducting materials and comparable to noble metals.
      Additionally, this substrate enabled the ultratrace detection regardless of the
      more Raman- or IR-active molecules and displayed distinct quantitative capacities
      for SERS and SEIRAS. High reproducibility of the SERS/SEIRAS spectra further
      confirmed the reliability and reproducibility of our substrates.

PMID- 28489394
TI  - Surface-Engineering of Ultrathin Gold Nanowires: Tailored Self-Assembly and
      Enhanced Stability.
AB  - Gold nanowires with a mean diameter of 1.7 nm were synthesized by reduction of
      HAuCl4 in a solution of oleylamine (OY) in hexane. A bilayer of oleylammonium
      chloride/oleylamine at the surface of the raw nanowires was evidenced by NMR and
      diffusion ordered spectroscopy (DOSY) experiments. After washing a monolayer of
      oleylammonium chloride remained at the surface of the nanowires. The
      oleylammonium chloride layer could be progressively replaced by a phosphine shell
      as evidenced with NMR and DOSY experiments, which are in good agreement with the
      adsorption energies given by density functional theory calculations. The
      nanowires crystallize into hexagonal superlattices with a lattice parameter that
      can be tailored depending on the ligand shell. Small-angle X-ray scattering
      showed the following lattice parameters: Au@OY+Cl-(OY) (a = 7.2 nm) > Au@TOPO/OY
      (a = 6.6 nm) > Au@ OY+Cl- (a = 4.1 nm) > Au@TOP (a = 3.75 nm). This is one of a
      few examples of surface modification of ultrathin nanowires that does not alter
      their morphology. Moreover, the nanowires coated with phosphines exhibited long
      time stability (at the opposite of other ligands like thiols) opening the way to
      more complex functionalization.

PMID- 28489395
TI  - Identification of Potent and Selective CYP1A1 Inhibitors via Combined Ligand and
      Structure-Based Virtual Screening and Their in Vitro Validation in Sacchrosomes
      and Live Human Cells.
AB  - Target structure-guided virtual screening (VS) is a versatile, powerful, and
      inexpensive alternative to experimental high-throughput screening (HTS). To
      discover potent CYP1A1 enzyme inhibitors for cancer chemoprevention, a commercial
      library of 50 000 small molecules was utilized for VS guided by both ligand and
      structure-based strategies. For experimental validation, 300 ligands were
      proposed based on combined analysis of fitness scores from ligand based e
      pharmacophore screening and docking score, prime MMGB/SA binding affinity and
      interaction pattern analysis from structure-based VS. These 300 compounds were
      screened, at 10 MUM concentration, for in vitro inhibition of CYP1A1-Sacchrosomes
      (yeast-derived microsomal enzyme) in the ethoxyresorufin-O-de-ethylase assay.
      Thirty-two compounds displayed >50% inhibition of CYP1A1 enzyme activity at 10
      MUM. 2-Phenylimidazo-[1,2-a]quinoline (5121780, 119) was found to be the most
      potent with 97% inhibition. It also inhibited ~95% activity of CYP1B1 and CYP1A2,
      the other two CYP1 enzymes. The compound 5121780 (119) showed high selectivity
      toward inhibition of CYP1 enzymes with respect to CYP2 and CYP3 enzymes (i.e.,
      there was no detectable inhibition of CYP2D6/CYP2C9/CYP2C19 and CYP3A4 at 10
      MUM). It was further investigated in live CYP-expressing human cell system, which
      confirmed that compound 5121780 (119) potently inhibited CYP1A1, CYP1A2, CYP1B1
      enzymes with IC50 values of 269, 30, and 56 nM, respectively. Like in
      Sacchrosomes, inhibition of CYP2D6/CYP2C9/CYP2C19 and CYP3A4 enzymes, expressed
      within live human cells, could hardly be detected at 10 MUM. The compound 119
      rescued CYP1A1 overexpressing HEK293 cells from CYP1A1 mediated benzo[a]pyrene
      (B[a]P) toxicity and also overcame cisplatin resistance in CYP1B1 overexpressing
      HEK293 cells. Molecular dynamics simulations of 5121780 (119) with CYP1 enzymes
      was performed to understand the interaction pattern to CYP isoforms. Results
      indicate that VS can successfully be used to identify promising CYP1A1
      inhibitors, which may have potential in the development of novel cancer chemo
      preventive agents.

PMID- 28489396
TI  - Fe/Cu-Mediated One-Pot Ketone Synthesis.
AB  - An Fe/Cu-mediated one-pot ketone synthesis was reported. Unlike Ni- and Pd
      mediated one-pot ketone syntheses, the reported Fe/Cu-mediated method allowed
      selective activation and coupling of alkyl iodides over vinyl iodides. The newly
      developed one-pot ketone synthesis was applied to a synthesis of vinyl
      iodide/ketone 13, the left half of halichondrin B, as well as vinyl iodide/ketone
      8a, the C20-C26 building block of halichondrins.

PMID- 28489397
TI  - Amine-Controlled Divergent Reaction: Iminolactonization and Olefination in the
      Presence of a Cu(I) Catalyst.
AB  - alpha-Bromoamides and styrenes underwent iminolactonization reactions
      (carbooxygenation), in which simultaneous C-C and C-O formation occurred in the
      presence of a copper catalyst with triethylamine as the base. Conversely,
      olefination reactions occurred in the presence of a Cu catalyst with piperidine
      as the base. The selectivities in those reactions were very high.

PMID- 28489398
TI  - Simultaneously Enhancing Light Emission and Suppressing Efficiency Droop in GaN
      Microwire-Based Ultraviolet Light-Emitting Diode by the Piezo-Phototronic Effect.
AB  - Achievement of p-n homojuncted GaN enables the birth of III-nitride light
      emitters. Owing to the wurtzite-structure of GaN, piezoelectric polarization
      charges present at the interface can effectively control/tune the optoelectric
      behaviors of local charge-carriers (i.e., the piezo-phototronic effect). Here, we
      demonstrate the significantly enhanced light-output efficiency and suppressed
      efficiency droop in GaN microwire (MW)-based p-n junction ultraviolet light
      emitting diode (UV LED) by the piezo-phototronic effect. By applying a -0.12%
      static compressive strain perpendicular to the p-n junction interface, the
      relative external quantum efficiency of the LED is enhanced by over 600%.
      Furthermore, efficiency droop is markedly reduced from 46.6% to 7.5% and
      corresponding droop onset current density shifts from 10 to 26.7 A cm-2. Enhanced
      electrons confinement and improved holes injection efficiency by the piezo
      phototronic effect are revealed and theoretically confirmed as the physical
      mechanisms. This study offers an unconventional path to develop high efficiency,
      strong brightness and high power III-nitride light sources.

PMID- 28489399
TI  - Synthesis of Tetraaza[8]circulenes from Tetrathia[8]circulenes through an SNAr
      Based Process.
AB  - The synthesis of highly planar tetraaza[8]circulenes from tetrathia[8]circulenes
      through oxidation followed by a nucleophilic aromatic substitution reaction with
      arylamines is presented. Photophysical and electrochemical properties of
      tetraaza[8]circulenes were investigated and compared to those of
      tetrathia[8]circulenes. The tetraaza[8]circulene exhibited bright fluorescence
      both in solution and solid states.

PMID- 28489400
TI  - Antirotaviral Activity of Bovine and Ovine Dairy Byproducts.
AB  - Rotaviral gastroenteritis is associated with significant morbidity in developed
      countries and a high rate of infant mortality in developing countries. Diverse
      studies have demonstrated that a wide range of milk-derived fractions exhibit
      antirotaviral activity. The present study shows the antirotaviral activity of
      some bovine and ovine dairy byproducts, buttermilk, butter serum, and milk fat
      globule membrane (MFGM), and evaluates the effect of cream washing and heat
      treatment on that activity. Furthermore, the rotavirus-neutralizing activity was
      evaluated for some MFGM proteins, such as xanthine oxidase and lactophorin. Ovine
      and bovine buttermilk reached rotavirus-neutralizing values of 51.3 and 32.2%, at
      1 mg/mL, respectively. The cream washing process led to a significant decrease in
      the antirotaviral activity of fractions. This activity was also influenced by
      heat treatment. Treatment at 75  degrees C for 20 s caused 24.6 and 36.1%
      decreases of activity in bovine and ovine buttermilk, respectively, and 85 
      degrees C for 10 min caused decreases of 80.9 and 79.0% in both fractions,
      respectively.

PMID- 28489401
TI  - Molecular Dynamics-Markov State Model of Protein Ligand Binding and Allostery in
      CRIB-PDZ: Conformational Selection and Induced Fit.
AB  - Conformational selection and induced fit are well-known contributors to ligand
      binding and allosteric effects in proteins. Molecular dynamics (MD) simulations
      now enable the theoretical study of protein-ligand binding in terms of ensembles
      of interconverting microstates and the population shifts characteristic of
      "dynamical allostery." Here we investigate protein-ligand binding and allostery
      based on a Markov state model (MSM) with states and rates obtained from all-atom
      MD simulations. As an exemplary case, we consider the single domain protein par-6
      PDZ with and without ligand and allosteric effector. This is one of the smallest
      proteins in which allostery has been experimentally observed. In spite of the
      increased complexity intrinsic to a statistical ensemble perspective, we find
      that conformational selection and induced fit mechanisms can be readily
      identified in the analysis. In the nonallosteric pathway, MD-MSM shows that PDZ
      binds ligand via conformational selection. However, the allosteric pathway
      requires an activation step that involves a conformational change induced by the
      allosteric effector Cdc42. Once in the allosterically activated state, we find
      that ligand binding can proceed by conformational selection. Our MD-MSM model
      predicts that allostery in this and possibly other systems involves both induced
      fit and conformational selection, not just one or the other.

PMID- 28489402
TI  - Iodine-Catalyzed Facile Approach to Sulfones Employing TosMIC as a Sulfonylating
      Agent.
AB  - A novel iodine-catalyzed functionalization of a variety of olefins and alkynes
      and direct decarboxylative functionalization of cinnamic and propiolic acids with
      TosMIC to provide access to various vinyl, allyl, and beta-iodo vinylsulfones is
      described. This simple, efficient, and environmentally benign approach employing
      inexpensive molecular iodine as a catalyst demonstrates a versatile protocol for
      the synthesis of highly valuable sulfones, rendering it attractive to both
      synthetic and medicinal chemistry.

PMID- 28489403
TI  - Development of a Chlorantraniliprole Microcapsule Formulation with a High Loading
      Content and Controlled-Release Property.
AB  - Microcapsule formulations have been widely developed and used in agriculture to
      improve pesticide utilization and reduce environmental pollution. However,
      commercial formulations of chlorantraniliprole (CAP) are only traditional
      formulations due to poor solubility of CAP in organic solvents. Here, adopting a
      solid in oil in water (S/O/W) double-emulsion method combined with premix
      membrane emulsion, we successfully constructed CAP microcapsule formulations with
      a high loading content. The microcapsule formulations with good light and thermal
      stability showed a significantly sustained release for a long period, which could
      be optimally regulated by tuning the surface porosity and size of the porous
      microcapsules. Bioassay studies showed that control efficacy of the porous
      microcapsule formulations against Plutella xylostella was superior to that of the
      commercial formulation. These results demonstrated that such a porous
      microcapsule delivery system should have great potential for further exploration
      as a commercial CAP formulation.

PMID- 28489404
TI  - Synthetic Routes toward Acidic Pentasaccharide Related to the O-Antigen of E.
      coli 120 Using One-Pot Sequential Glycosylation Reactions.
AB  - Concise syntheses of the acidic pentasaccharide, related to the O-antigenic
      polysaccharide of Escherichia coli 120, as its p-methoxyphenyl glycoside, have
      been achieved using a one-pot sequential glycosylation technique. The
      glycosylations have been accomplished either by the activation of the
      thioglycosides using NIS in the presence of FeCl3 or by a preactivation by Ph2SO,
      TTBP, Tf2O, and the activation of the trichloroacetimidates using FeCl3 alone or
      TMSOTf. Most of the intermediate steps are high yielding, and the stereo outcomes
      of the glycosylation steps were excellent. The syntheses of the targeted
      pentasaccharide have been performed with both three- and four-component, one-pot
      sequential glycosylation reactions, and in both cases, the orthogonal
      glycosylations are carried out utilizing catalytic activity of FeCl3. A late
      stage TEMPO-mediated regioselective oxidation has been performed to achieve the
      required uronic acid motif.

PMID- 28489405
TI  - Charge Carrier Relaxation in Different Plasticized PEO/PVDF-HFP Blend Solid
      Polymer Electrolytes.
AB  - In this article, we report first the effect of concentration of ethylene
      carbonate plasticizer on conduction and relaxation of charge carriers in PEO/PVDF
      HFP-LiClO4 blend electrolytes. Second, the results for different plasticizers,
      such as ethylene carbonate, propylene carbonate, and dimethyle carbonate, on the
      conductivity and relaxation in these blend electrolytes are compared. We have
      followed a new approach for the analysis of the conductivity data. The frequency
      dependent conductivity is analyzed using random free-energy barrier model, taking
      into consideration the low frequency polarization effect. The temperature
      dependences of the ionic conductivity and the relaxation time obtained from the
      model exhibit Vogel-Tammann-Fulcher behavior. Using the scaling of the ac
      conductivity spectra it is observed that the relaxation dynamics of charge
      carriers in blend electrolytes are independent of temperature but depend on the
      nature of plasticizers. The electric modulus is studied using Havriliak-Negami
      function for the understanding of ionic relaxation. The modulus data are also
      analyzed using nonexponential Kohlrausch-Williams-Watts function. The temperature
      dependence of the relaxation time obtained from modulus analysis follows Vogel
      Tammann-Fulcher relation for all plasticized electrolytes. It is observed that
      the stretched exponent is much lower than unity, which suggests that charge
      carrier relaxation is highly nonexponential in these plasticized electrolytes.

PMID- 28489406
TI  - Initiation Reactions in Acetylene Pyrolysis.
AB  - In gas-phase combustion systems the interest in acetylene stems largely from its
      role in molecular weight growth processes. The consensus is that above 1500 K
      acetylene pyrolysis starts mainly with the homolytic fission of the C-H bond
      creating an ethynyl radical and an H atom. However, below ~1500 K this reaction
      is too slow to initiate the chain reaction. It has been hypothesized that instead
      of dissociation, self-reaction initiates this process. Nevertheless, rigorous
      theoretical or direct experimental evidence is lacking, to an extent that even
      the molecular mechanism is debated in the literature. In this work we use
      rigorous ab initio transition-state theory master equation methods to calculate
      pressure- and temperature-dependent rate coefficients for the association of two
      acetylene molecules and related reactions. We establish the role of vinylidene,
      the high-energy isomer of acetylene in this process, compare our results with
      available experimental data, and assess the competition between the first-order
      and second-order initiation steps. We also show the effect of the rapid
      isomerization among the participating wells and highlight the need for time-scale
      analysis when phenomenological rate coefficients are compared to observed time
      scales in certain experiments.

PMID- 28489407
TI  - High-Yield Synthesis of Janus Dendritic Mesoporous Silica@Resorcinol-Formaldehyde
      Nanoparticles: A Competing Growth Mechanism.
AB  - Recently, Janus nanostructures that possess two or more different surface
      functions have attracted enormous attention because of their unique structures
      and promising applications in diverse fields. In this work, we present that Janus
      structured dendritic mesoporous silica@resorcinol-formaldehyde (DMS@RF)
      nanoparticles can be prepared through a simple one-pot colloidal method. The
      Janus DMS@RF nanoparticle shows a bonsai-like morphology which consists of a
      dendritic mesoporous silica part and a spherical RF part. After a systematic
      study on the growth process, we proposed a competing growth mechanism that
      accounts for the formation of Janus nanostructures. It is believed that suitable
      polymerization rate of silica and RF resin is critical. Based on the competing
      growth mechanism, eccentric and concentric core-shell nanostructures have been
      successfully prepared by tuning the polymerization rates of silica and RF,
      respectively. Metal-contained ternary Janus nanoparticles that might be used for
      catalysis have also been prepared. This research may pave the way for the
      practical applications of delicate nanomaterials with desired structures and
      properties.

PMID- 28489408
TI  - Thermodynamics and Mechanisms of the Interactions between Ultrasmall Fluorescent
      Gold Nanoclusters and Human Serum Albumin, gamma-Globulins, and Transferrin: A
      Spectroscopic Approach.
AB  - Noble metal nanoclusters (NCs) show great promise as nanoprobes for bioanalysis
      and cellular imaging in biological applications due to ultrasmall size, good
      photophysical properties, and excellent biocompatibility. In order to achieve a
      comprehensive understanding of possible biological implications, a series of
      spectroscopic measurements were conducted under different temperatures to
      investigate the interactions of Au NCs (~1.7 nm) with three model plasmatic
      proteins (human serum albumin (HSA), gamma-globulins, and transferrin). It was
      found that the fluorescence quenching of HSA and gamma-globulins triggered by Au
      NCs was due to dynamic quenching mechanism, while the fluorescence quenching of
      transferrin by Au NCs was a result of the formation of a Au NC-transferrin
      complex. The apparent association constants of the Au NCs bound to HSA, gamma
      globulins, and transferrin demonstrated no obvious difference. Thermodynamic
      studies demonstrated that the interaction between Au NCs and HSA (or gamma
      globulins) was driven by hydrophobic forces, while the electrostatic interactions
      played predominant roles in the adsorption process for transferrin. Furthermore,
      it was proven that Au NCs had no obvious interference in the secondary structures
      of these three kinds of proteins. In turn, these three proteins had a minor
      effect on the fluorescence intensity of Au NCs, which made fluorescent Au NCs
      promising in biological applications owing to their chemical and photophysical
      stability. In addition, by comparing the interactions of small molecules, Au NCs,
      and large nanomaterials with serum albumin, it was found that the binding
      constants were gradually increased with the increase of particle size. This work
      has elucidated the interaction mechanisms between nanoclusters and proteins, and
      shed light on a new interaction mode different from the protein corona on the
      surface of nanoparticles, which will highly contribute to the better design and
      applications of fluorescent nanoclusters.

PMID- 28489409
TI  - Ultralow Stress, Thermally Stable Cross-Linked Polymer Films of
      Polydivinylbenzene (PDVB).
AB  - Although closely related to polystyrene, poly(divinylbenzene) (PDVB) has found
      limited utility due to the difficulties associated with its synthesis. As a
      highly cross-linked polymer, PDVB is infusible and insoluble and thus nearly
      impossible to shape into films by either melt or solvent-based processes. Here,
      we report the initiated chemical vapor deposition (iCVD) of nearly stress-free,
      highly transparent, free-standing films of PDVB up to 25 MUm thick. Films
      initially grow under tensile intrinsic stress but become more compressive with
      thickness and eventually converge to zero-stress values once they reach >=10 MUm
      in thickness. Upon initial heating, the evaporative loss of unreacted monomer
      left in the polymer matrix induces between 35 and 45 MPa of tensile stress in the
      films. Afterward, subsequent heating cycles induce reversible stress and film
      expansion behaviors. We estimate the degree of cross-linking to be 44%, resulting
      in high thermal stability (up to 300  degrees C) and mechanical stiffness
      (Young's modulus of 5.2 GPa). The low stress combined with high cross-linking
      makes iCVD PDVB an excellent candidate for protective coatings in harsh
      environments.

PMID- 28489410
TI  - Strategically Designing a Pumpless Microfluidic Device on an "Inert"
      Polypropylene Substrate with Potential Application in Biosensing and Diagnostics.
AB  - This study is an attempt to make a step forward to implement the very immature
      concept of pumpless transportation of liquid into a real miniaturized device or
      lab-on-chip (LOC) on a plastic substrate. "Inert" plastic materials such as
      polypropylene (PP) are used in a variety of biomedical applications but their
      surface engineering is very challenging. Here, it was demonstrated that with a
      facile innovative wettability patterning route using fluorosilanized UV
      independent TiO2 nanoparticle coating it is possible to create wedge-shaped open
      microfluidic tracks on inert solid surfaces for low-cost biomedical devices (lab
      on-plastic). For the future miniaturization and integration of the tracks into a
      device, a variety of characterization techniques were used to not only
      systematically study the surface patterning chemistry and topography but also to
      have a clear knowledge of its biological interactions and performance. The effect
      of such surface architecture on the biological performance was studied in terms
      of static/dynamic protein (bovine serum albumin) adsorption, bacterial
      (Staphylococcus aureus and Staphylococcus epidermidis) adhesion, cell viability
      (using HeLa and MCF-7 cancer cell lines as well as noncancerous human fibroblast
      cells), and cell patterning (Murine embryonic fibroblasts). Strategies are
      discussed for incorporating such a confined track into a diagnostic device in
      which its sensing portion is based on protein, microorganism, or cells. Finally,
      for the proof-of-principle of biosensing application, the well-known high
      affinity molecular couple of BSA-antiBSA as a biological model was employed.

PMID- 28489411
TI  - gCoda: Conditional Dependence Network Inference for Compositional Data.
AB  - The increasing quality and the reducing cost of high-throughput sequencing
      technologies for 16S rRNA gene profiling enable researchers to directly analyze
      microbe communities in natural environments. The direct interactions among
      microbial species of a given ecological system can help us understand the
      principles of community assembly and maintenance under various conditions.
      Compositionality and dimensionality of microbiome data are two main challenges
      for inferring the direct interaction network of microbes. In this article, we use
      the logistic normal distribution to model the background mechanism of microbiome
      data, which can appropriately deal with the compositional nature of the data. The
      direct interaction relationships are then modeled via the conditional dependence
      network under this logistic normal assumption. We then propose a novel penalized
      maximum likelihood method called gCoda to estimate the sparse structure of
      inverse covariance for latent normal variables to address the high dimensionality
      of the microbiome data. An effective Majorization-Minimization algorithm is
      proposed to solve the optimization problem in gCoda. Simulation studies show that
      gCoda outperforms existing methods (e.g., SPIEC-EASI) in edge recovery of inverse
      covariance for compositional data under a variety of scenarios. gCoda also
      performs better than SPIEC-EASI for inferring direct microbial interactions of
      mouse skin microbiome data.

PMID- 28489412
TI  - Brief review of fluid reasoning: Conceptualization, neurobasis, and applications.
AB  - In the early part of the twentieth century the value of nonverbal tests was
      initially recognized by Yoakum and Yerkes when they wrote how examinees could
      fail a verbal test of general ability because of limited skills in English. When
      these examinees were then tested with a nonverbal test of ability, they often
      performed well, and therefore this approach avoided "injustice by reason of
      relative unfamiliarity with English." Measuring cognitive ability with nonverbal
      measures that do not require verbal skills has been supported now for nearly a
      century. Research has demonstrated that a person's general ability can be
      measured validly and reliably without requiring the student to read, write, or
      speak. The neuroanatomical and neuro-anatomical basis for FR is well established
      and focuses on the frontal-parietal system, and the use of FR measures is a
      common practice. In this brief article the current conceptualization of Fluid
      Reasoning (FR) is examined, I suggest how popular used constructs on other common
      cognitive tests can be conceptualized as a variant of FR. Then, the general
      neuroanatomical substrates and networks are revisited, followed by summarizing
      some of the practical scenarios for measuring FR may be useful.

PMID- 28489413
TI  - Two year outcomes of poststroke writing and reading disorders.
AB  - Poststroke language disorders are frequent and include aphasia, alexia, agraphia,
      and acalculia. These disorders refer to an acquired inability to read, write and
      calculate. In this study, we evaluated the two year outcomes of writing and
      reading disorders in poststroke patients, the natural course, recovery and
      mortality. We evaluated all the patients with stroke who were admitted to the
      Department of Neurology, University Clinical Centre Tuzla in period of six
      months, who developed poststroke alexia, agraphia, acalculia, or different
      combinations of these language disorders. Outcome of these patients was evaluated
      again after 24 months. For clinical assessment of alexia, agraphia, and acalculia
      we used Minnesota Test for Differential Diagnosis of Aphasia. We investigated 59
      (30.5%) of 193 stroke patients with alexia, agraphia, acalculia, and
      combinations. Outcome of these patients after 24 months was: 37 (62.7%) died, 13
      (22%) fully recovered, and 9 (15.3%) of them retained the same disorder or
      developed dementia or blindness. Binary logistic regression analysis showed that
      patients with combined language disorders had significantly higher mortality. The
      main factors influencing language disorders recovery in this study are initial
      severity of reading, writing and calculation impairment, age, neglect, and level
      of education.

PMID- 28489414
TI  - On Proportions of Fit Individuals in Population of Mutation-Based Evolutionary
      Algorithm with Tournament Selection.
AB  - In this article, we consider a fitness-level model of a non-elitist mutation-only
      evolutionary algorithm (EA) with tournament selection. The model provides upper
      and lower bounds for the expected proportion of the individuals with fitness
      above given thresholds. In the case of so-called monotone mutation, the obtained
      bounds imply that increasing the tournament size improves the EA performance. As
      corollaries, we obtain an exponentially vanishing tail bound for the Randomized
      Local Search on unimodal functions and polynomial upper bounds on the runtime of
      EAs on the 2-SAT problem and on a family of Set Cover problems proposed by E.
      Balas.

PMID- 28489415
TI  - Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis.
AB  - Maintenance of tissue-specific organ lipid compositions characterizes mammalian
      lipid homeostasis. The lungs and liver synthesize mixed phosphatidylcholine (PC)
      molecular species that are subsequently tailored for function. The lungs
      progressively enrich disaturated PC directed to lamellar body surfactant stores
      before secretion. The liver accumulates polyunsaturated PC directed to very-low
      density lipoprotein assembly and secretion, or to triglyceride stores. In each
      tissue, selective PC species enrichment mechanisms lie at the heart of effective
      homeostasis. We tested for potential coordination between these spatially
      separated but possibly complementary phenomena under a major derangement of lung
      PC metabolism, pulmonary alveolar proteinosis (PAP), which overwhelms homeostasis
      and leads to excessive surfactant accumulation. Using static and dynamic
      lipidomics techniques, we compared (1) tissue PC compositions and contents, and
      (2) in lungs, the absolute rates of synthesis in both control mice and the
      granulocyte-macrophage colony-stimulating factor knockout model of PAP.
      Significant disaturated PC accumulation in bronchoalveolar lavage fluid, alveolar
      macrophage, and lavaged lung tissue occurred alongside increased PC synthesis,
      consistent with reported defects in alveolar macrophage surfactant turnover.
      However, microscopy using oil red O staining, coherent anti-Stokes Raman
      scattering, second harmonic generation, and transmission electron microscopy also
      revealed neutral-lipid droplet accumulations in alveolar lipofibroblasts of
      granular macrophage colony-stimulating factor knockout animals, suggesting that
      lipid homeostasis deficits extend beyond alveolar macrophages. PAP plasma PC
      composition was significantly polyunsaturated fatty acid enriched, but the
      content was unchanged and hepatic polyunsaturated fatty acid-enriched PC content
      increased by 50% with an accompanying micro/macrovesicular steatosis and a
      fibrotic damage pattern consistent with nonalcoholic fatty liver disease. These
      data suggest a hepatopulmonary axis of PC metabolism coordination, with wider
      implications for understanding and managing lipid pathologies in which compromise
      of one organ has unexpected consequences for another.

PMID- 28489416
TI  - Concordance validity of PVTs in a sample of veterans referred for mild TBI.
AB  - Concordance validity of commonly used performance validity tests (PVTs) was
      assessed in a sample of Operation Enduring Freedom/Operation Iraqi
      Freedom/Operation New Dawn (OEF/OIF/OND) veterans referred to an mTBI screening
      clinic in a south-eastern Veterans Affairs hospital. Veteran service members
      (total n = 184) completed the Rey-15, Repeatable Battery of the Assessment for
      Neuropsychological Status Effort Index (RBANS EI), and Reliable Digit Span (RDS)
      from the Wechsler Intelligence Scales. Kappa coefficients and percentage of
      agreement were established to determine the level of concordance between the
      three measures. PVT failure rate ranged from 7.4% of the sample (Rey-15) to 26.1%
      (RBANS EI Liberal). The highest concordance was found between the Rey 15 and
      RBANS EI "highly suspicious" cut-off, with the lowest agreement noted between all
      PVTs and the RBANS EI "liberal" cut-score. All concordance coefficients fell
      within the fair to moderate levels. Overall, the observed agreement between the
      explored measures was generally consistent with or greater than other studies of
      PVT concordance. Given the rates of concordance, the current results continue to
      suggest that PVTs are likely to measure a construct separate from the typical
      cognitive domains.

PMID- 28489418
TI  - Studies on the Clustering Algorithm for Analyzing Gene Expression Data with a
      Bidirectional Penalty.
AB  - This article reports a new clustering method based on the k-means algorithm to
      high-dimensional gene expression data. The proposed approach makes use of
      bidirectional penalties to constrain the number of clusters and centroids of
      clusters to simultaneously determine the unknown number of clusters and handle
      large amounts of noise in gene expression data. Numeric studies indicate that
      this algorithm not only performs better in clustering but is also comparable to
      other approaches in its ability to obtain the correct number of clusters and
      correct signal features. Finally, we apply the proposed approach to analyze two
      benchmark gene expression datasets. These analyses again indicate that the
      proposed algorithm performs well in clustering high-dimensional gene expression
      data with an unknown number of clusters.

PMID- 28489417
TI  - A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic
      Response in Pulmonary Alveolar Proteinosis.
AB  - RATIONALE: A useful semiquantitative method of using computed tomographic (CT)
      images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP)
      has not been established, although the extent score or grading score of ground
      glass opacities has been used. OBJECTIVES: The purpose of this study was to
      establish a semiquantitative method for evaluating therapeutic response in PAP.
      METHODS: CT scans were obtained within 1 month before and after therapy from 32
      patients with PAP who participated in a multicenter phase II trial of granulocyte
      macrophage colony-stimulating factor inhalation therapy. The scans were evaluated
      by two chest radiologists independently. Increased parenchymal opacity was
      evaluated on the basis of its intensity and extent (CT grade), and the severity
      scores were compared with CT scores based on the extent alone (CT extent), as
      well as on the basis of physiological and serological results. RESULTS: CT grade
      score and CT extent score had significant correlation with diffusing capacity of
      the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent
      predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The
      change in CT grade score between pre- and post-treatment examinations (DeltaCT
      grade) correlated better with difference of PaO2 between pre- and post-treatment
      examinations (DeltaPaO2) than DeltaCT extent (difference of CT extent score
      between pre- and post-treatment examinations). In univariate analysis, DeltaCT
      grade, DeltaCT extent, DeltaKL-6, Delta%DlCO, Delta%VC, and change in surfactant
      protein D correlated significantly with DeltaPaO2. In multivariate analysis,
      DeltaCT grade and DeltaKL-6 correlated more closely with DeltaPaO2. CONCLUSIONS:
      Although a number of CT variables were collected, the currently proposed grading
      system that correlates well with PaO2 should be viewed as a retrospective scoring
      system that needs future validation with another PAP cohort.

PMID- 28489419
TI  - When is a novel psychometric measure needed? A preliminary analysis regarding the
      Cognitive Assessment for Stroke Patients (CASP) battery compared with MMSE and
      MoCA.
AB  - The need for quick tools to sketch an early but accurate cognitive profile of
      patients who suffered brain damage or head trauma is of primary importance.
      Nonetheless, in the Italian context, the most-diffused screening tools are still
      those originally devised to diagnose dementia. The present pilot study then aimed
      at investigating the potential and feasibility of a novel screening battery, the
      Cognitive Assessment for Stroke Patients (CASP), in a sample of Italian patients
      by comparing it to Mini-Mental State Examination (MMSE) and Montreal Cognitive
      Assessment (MoCA) tests. A total of 29 neurology patients took part in the study.
      Participants underwent a screening procedure including the administration of
      MMSE, MoCA, and CASP. Data analysis suggested that the scores of the Italian
      version of the CASP are relatively less affected by the presence of language
      difficulties-common sequelae of stroke and head traumas-with respect to MMSE and
      MoCA ones. Furthermore, CASP scores proved to be highly correlated with both MMSE
      and MoCA scores, showing good clinical potential. Finally, the outcomes of
      administered tests proved not to be influenced by etiology or gender, and CASP
      scores showed a diminishing trend related to patients' age and a positive
      association with patients' education.

PMID- 28489420
TI  - Anthropologists in MalariaWorld.
AB  - The history of anthropological contributions to the study of malaria is reviewed
      in terms of three additive phases: (1) cultural-historical analyses; (2) applied
      work aimed at the improvement of malaria control programs; and (3) introduction
      of critical medical anthropological themes about malaria control. The critical
      approaches include themes of the cultural construction of reality-the definition
      of "malaria"; political-economic structures in health inequalities; and an
      emphasis on social factors as exemplified in the present special issue. The
      contemporary culture of malaria researchers and programs-called MalariaWorld-is
      described in terms of economy, social organization, and belief system. Five
      common features of articles in this special issue are described as unique
      anthropological features that are key for understanding MalariaWorld.

PMID- 28489421
TI  - Mechanisms and Functions of Spatial Protein Quality Control.
AB  - A healthy proteome is essential for cell survival. Protein misfolding is linked
      to a rapidly expanding list of human diseases, ranging from neurodegenerative
      diseases to aging and cancer. Many of these diseases are characterized by the
      accumulation of misfolded proteins in intra- and extracellular inclusions, such
      as amyloid plaques. The clear link between protein misfolding and disease
      highlights the need to better understand the elaborate machinery that manages
      proteome homeostasis, or proteostasis, in the cell. Proteostasis depends on a
      network of molecular chaperones and clearance pathways involved in the
      recognition, refolding, and/or clearance of aberrant proteins. Recent studies
      reveal that an integral part of the cellular management of misfolded proteins is
      their spatial sequestration into several defined compartments. Here, we review
      the properties, function, and formation of these compartments. Spatial
      sequestration plays a central role in protein quality control and cellular
      fitness and represents a critical link to the pathogenesis of protein aggregation
      linked diseases.

PMID- 28489422
TI  - Mechanisms of automaticity and anticipatory control in fluid intelligence.
AB  - The constructs of fluid (Gf) and crystalized (Gc) intelligence represent an early
      attempt to describe the mechanisms of problem solving in the vertebrate brain.
      Modern neuroscience demonstrates that problem solving involves interplay between
      the mechanisms of automaticity and anticipatory control, enabling nature's
      elegant solution to the challenges animals face in their environment. Studies of
      neural functioning are making clear the primary role of cortical-subcortical
      interactions in the manifestation of intelligent behavior in humans and other
      vertebrates. A tridimensional model of intelligent problem solving is explored,
      wherein the basal ganglia system (BGS) and cerebrocerebellar system (CCS)
      interact within large scale brain networks. The BGS and CCS work together to
      enable automaticity to occur. The BGS enables the organism to learn what to do
      through a powerful instrumental learning system. The BGS also regulates when
      behavior is released through an inhibitory system which is incredibly sensitive
      to context. The CCS enables the organism to learn how to perform adaptive
      behaviors. Internal cerebellar models enable gradual improvements in the quality
      of behavioral output. The BGS and CCS interact within large scale brain networks,
      including the dorsal attention network (DAN), ventral attention network (VAN),
      default mode network (DMN) and frontoparietal network (FPN). The interactions of
      these systems enable vertebrate organisms to develop a vast array of complex
      adaptive behaviors. The benefits and importance of developing clinical tests to
      measure the integrity of these systems is considered.

PMID- 28489423
TI  - Is rheumatoid arthritis associated with reduced immunogenicity of the influenza
      vaccination? A systematic review and meta-analysis.
AB  - OBJECTIVE: To determine whether immunogenicity and safety of the influenza
      vaccination in rheumatoid arthritis (RA) patients are significantly different
      from those in a healthy population. METHODS: PubMed, MEDLINE, Embase, Cochrane
      Library and Web of Science were searched on 31 August 2016. Studies were included
      when they met the inclusion criteria. Two reviewers independently extracted data
      on study characteristics, methodological quality and outcomes. The primary
      outcome was seroprotection (SP) rate after immunization. RESULTS: Thirteen
      studies were included. The SP rates did not significantly differ between the RA
      patients and healthy controls for the H3N2 (RR = 0.96, 95% CI, 0.82 to 1.13, p =
      .64) and B strain (RR = 0.95, 95% CI 0.84 to 1. 08, p = .44). Nevertheless, RA
      was associated with a significant decrease in SP rate for the H1N1 strain (RR =
      0.72, 95% CI 0.60 to 0.86, p < .001). RA patients receiving immunosuppressive
      chemotherapy, TNF blockers, rituximab and other biologics responded to the H1N1
      strain significantly less than healthy controls in SP rate, whereas those
      receiving steroids did not. Non-adjuvanted vaccination had a significantly lower
      SP rate than in healthy controls, whereas adjuvanted vaccination did not. RA was
      associated with an increase in adverse events (RR = 1.77, 95% CI 1.02 to 3.08, p
      = .04). CONCLUSIONS: Immunogenicity was significantly different between RA
      patients and healthy controls for the H1N1 strain, but not for the H3N2 or B
      strains. Adverse event rates were higher in RA patients. Adjuvant and special
      kinds of immunosuppressive biologics may play an important role in immunogenicity
      of inactivated influenza vaccines for RA patients.

PMID- 28489424
TI  - A novel pH-responsive hydrogel-based on calcium alginate engineered by the
      previous formation of polyelectrolyte complexes (PECs) intended to vaginal
      administration.
AB  - This work aimed to develop a calcium alginate hydrogel as a pH responsive
      delivery system for polymyxin B (PMX) sustained-release through the vaginal
      route. Two samples of sodium alginate from different suppliers were
      characterized. The molecular weight and M/G ratio determined were, approximately,
      107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer
      rheological investigations were further performed through the preparation of
      hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the
      acquisition of pseudoplastic viscous system able to acquiring a differential
      structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel
      (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation
      between alginate and PMX followed by crosslinking with calcium chloride. This
      system exhibited a morphology with variable pore sizes, ranging from 100 to 200
      MUm and adequate syringeability. The hydrogel liquid uptake ability in an acid
      environment was minimized by the previous PECs formation. In vitro tests
      evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the
      system was able to sustain the release up to 6 days. A burst release was observed
      at pH 7.4 and drug release was driven by an anomalous transport, as determined by
      the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model
      and drug transport was driven by Fickian diffusion. The calcium alginate
      hydrogels engineered by the previous formation of PECs showed to be a promising
      platform for sustained release of cationic drugs through vaginal administration.

PMID- 28489425
TI  - Tissue-specific effects of estrogen on glycerol channel aquaporin 7 expression in
      an ovariectomized mouse model of menopause.
AB  - OBJECTIVE: Elevated fat mass and redistribution of body fat are commonly observed
      in postmenopausal women. Aquaporin 7 (AQP7), a unique glycerol permeable integral
      membrane protein, has been associated with the onset of obesity. We hypothesized
      that estrogen supplementation could counteract this fat accumulation and
      redistribution through tissue-specific modulation of AQP7. METHODS: We measured
      fat depot weight, adipocyte size, and the expression of AQP7 and glycerol kinase
      (GK) in visceral and subcutaneous fat tissues of ovariectomized mice supplemented
      with or without 17beta-estradiol. RESULTS: Removal of the ovaries resulted in a
      significant decrease in AQP7 expression and an increase in GK expression in
      visceral adipocyte tissue; expression of AQP7 and GK in subcutaneous adipose
      tissue remained unaltered. Supplementation with estrogen significantly restored
      the visceral, but not subcutaneous, fat depot mass and adipocyte size to those of
      sham-operated mice. A marked increase in the expression of AQP7 and a reduction
      of GK were observed selectively in the visceral fat depots in estrogen-treated
      mice. CONCLUSIONS: Our results suggest that estrogen has tissue-specific effects
      on AQP7 expression, and modulation of AQP7 by estrogen alters the balance of
      adipocyte metabolism between adipose tissue depots.

PMID- 28489426
TI  - Preparation, characterization and in vitro evaluation of microemulsion of
      raloxifene hydrochloride.
AB  - Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator which
      is orally used for treatment of osteoporosis and prevention of breast cancer. The
      drug has low aqueous solubility and bioavailability. The aim of the present study
      is to formulate and characterize oil-in-water microemulsion systems for oral
      delivery of RLX. To enhance the drug aqueous solubility, microemulsion based on
      sesame oil was prepared. Sesame oil and Tween 80 were selected as the drug
      solvent oil and surfactant, respectively. In the first and second formulations,
      Edible glycerin and Span 80 were applied as co-surfactant, respectively. Pseudo
      ternary phase diagrams showed that the best surfactant/co-surfactant ratios in
      the first and second formulations were 4:1 and 9:1, respectively. The particle
      size of all free drug-loaded and drug loaded samples were in the range of 31.25
      +/- 0.3 nm and 60.9 +/- 0.1 nm, respectively. Electrical conductivity coefficient
      and refractive index of all microemulsion samples confirmed the formation of oil
      in-water type of microemulsion. In vitro drug release profile showed that after
      24 hours, 46% and 63% of the drug released through the first formulation in 0.1%
      (w/v) Tween 80 in distilled water as a release medium and phosphate buffer
      solution (PBS) at pH = 5.5, respectively. These values were changed to 57% and
      98% for the second formulation. Results confirmed that the proposed microemulsion
      system containing RLX could improve and control the drug release profile in
      comparison to conventional dosage form.

PMID- 28489427
TI  - Air Pollution from Livestock Farms Is Associated with Airway Obstruction in
      Neighboring Residents.
AB  - RATIONALE: Livestock farm emissions may not only affect respiratory health of
      farmers but also of neighboring residents. OBJECTIVES: To explore associations
      between spatial and temporal variation in pollutant emissions from livestock
      farms and lung function in a general, nonfarming, rural population in the
      Netherlands. METHODS: We conducted a cross-sectional study in 2,308 adults (age,
      20-72 yr). A pulmonary function test was performed measuring prebronchodilator
      and post-bronchodilator FEV1, FVC, FEV1/FVC, and maximum mid-expiratory flow
      (MMEF). Spatial exposure was assessed as (1) number of farms within 500 m and
      1,000 m of the home, (2) distance to the nearest farm, and (3) modeled annual
      average fine dust emissions from farms within 500 m and 1,000 m of the home
      address. Temporal exposure was assessed as week-average ambient particulate
      matter <10 MUm in diameter and ammonia (NH3) concentrations before lung function
      measurements. Data were analyzed with generalized additive models (smoothing).
      MEASUREMENTS AND MAIN RESULTS: A negative association was found between the
      number of livestock farms within a 1,000-m buffer from the home address and MMEF,
      which was more pronounced in participants without atopy. No associations were
      found with other spatial exposure variables. Week-average particulate matter <10
      MUm in diameter and NH3 levels were negatively associated with FEV1, FEV1/FVC,
      and MMEF. In a two-pollutant model, only NH3 remained associated. A 25-MUg/m3
      increase in NH3 was associated with a 2.22% lower FEV1 (95% confidence interval, 
      3.69 to -0.74), FEV1/FVC of -1.12% (-1.96 to -0.28), and MMEF of -5.67% (-8.80 to
      -2.55). CONCLUSIONS: Spatial and temporal variation in livestock air pollution
      emissions are associated with lung function deficits in nonfarming residents.

PMID- 28489429
TI  - Treatment of Hallucinations in the Context of Anxiety: When Less Is More.

PMID- 28489428
TI  - A Single-Molecule View of Genome Editing Proteins: Biophysical Mechanisms for
      TALEs and CRISPR/Cas9.
AB  - Exciting new advances in genome engineering have unlocked the potential to
      radically alter the treatment of human disease. In this review, we discuss the
      application of single-molecule techniques to uncover the mechanisms behind two
      premier classes of genome editing proteins: transcription activator-like effector
      nucleases (TALENs) and the clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated system (Cas). These technologies have
      facilitated a striking number of gene editing applications in a variety of
      organisms; however, we are only beginning to understand the molecular mechanisms
      governing the DNA editing properties of these systems. Here, we discuss the DNA
      search and recognition process for TALEs and Cas9 that have been revealed by
      recent single-molecule experiments.

PMID- 28489430
TI  - From the Editor-in-Chief's Desk.

PMID- 28489433
TI  - Clinical News.

PMID- 28489432
TI  - Touching the elephant: The search for fluid intelligence.
AB  - Many constructs that we take for granted in modern neuropsychology, fluid
      intelligence among them, can best be explained by conceptionalizing them as a
      collection of task specific processes engaged in by an integrated recruited
      network involved in problem solving. Fractionalizing the network in an attempt to
      describe elements of its function leads to arbitrarily defined segments that may
      be interesting to discuss abstractly, but never occur independently in the real
      world operation of the system. We will seek to demonstrate that the construct of
      fluid intelligence is like that. It is a description of a type of operation of a
      network dedicated to solving problems and the composition of the network that is
      responsible for the activity changes in a task specific manner. As a result,
      fluid intelligence is not an independent skill, or a thing that lives on its own,
      or can be measured independently of the other things that contribute to the
      overall operation of the network as it seeks to solve problems.

PMID- 28489434
TI  - Is training the answer to everything?

PMID- 28489435
TI  - Improved emergency department patient care via rapid assessment and triage.

PMID- 28489436
TI  - Liver transplantation: post-transplant management.
AB  - Medical care for patients following liver transplantation is complex and requires
      a holistic approach to management. Patients and clinicians are faced with
      multiple challenges: immunosuppressive regimens must be optimized to avoid and
      treat graft rejection, the risk and atypical features of sepsis in the
      immunocompromised patient must be recognized, steps are required to reduce the
      recurrence of liver disease and the long-term increased risks of malignancy,
      renal failure and metabolic complications need managing. Despite the benefits of
      liver transplantation there are additional concerns regarding the impact upon
      quality of life. This review will focus upon the care of patients following liver
      transplantation. As these patients will present to a broad range of clinicians,
      an understanding of the common drugs used post-transplantation and general
      approach to management of these patients will be of benefit to the general
      clinical audience.

PMID- 28489437
TI  - Putting the mouth back into the body.

PMID- 28489438
TI  - Surgical issues in retrieval and implantation.
AB  - With increasing demand for organ transplantation and patients deteriorating or
      dying on the waiting list, organs are now being increasingly used from donors
      previously considered too marginal. This requires improvements to donor
      management during the retrieval process, and of the organ during transport and
      subsequent implantation, in order to maintain outcomes.

PMID- 28489439
TI  - Assessment of haemodynamic disturbance.

PMID- 28489440
TI  - Optimizing a career in surgery.

PMID- 28489441
TI  - Treatment of haemodynamic disturbance.

PMID- 28489442
TI  - How not to miss major spinal pathology in patients with back pain.

PMID- 28489444
TI  - Noise-induced hearing loss: a modern epidemic?
AB  - Hearing loss is an increasingly common problem in the UK, and noise-induced
      hearing loss is the second most common acquired cause. There is a greater burden
      on the younger population, as recreational noise exposure is an important
      contributor. New damaging hearing behaviours have emerged including loud music
      exposure at concerts, nightclubs and via personal music players. The mechanism of
      damage is thought to involve many diverse pathways, which include oxidative
      damage, mechanical shearing forces and glutamate excitotoxicity. Although no
      current treatment exists to reverse the damage caused, these pathways can be
      targeted by agents that are being trialled for use in post-exposure treatment and
      prevention, with conflicting results. Other preventative strategies are important
      in addressing damaging hearing behaviours, including 'safe listening' promotion
      with advocacy materials for young adults, and promoting safe listening devices.

PMID- 28489445
TI  - Mucosal malignant melanoma presenting with huge, fleshy, dark-red polyp in the
      nasal cavity.

PMID- 28489446
TI  - Liver transplantation: need, indications, patient selection and pre-transplant
      care.
AB  - Chronic or acute liver failure and primary liver cancers can be effectively
      managed with liver transplantation. The range of indications for liver
      transplantation is increasing but there is a mismatch between the numbers of
      available donations and current needs. Specific criteria for listing patients
      exist but, at minimum, the predicted mortality without transplantation must
      exceed that with transplantation, coupled with a 50% predicted 5-year survival
      following liver transplantation. The risk posed by liver disease must be weighed
      against the risk of liver transplantation, considering the patient's
      comorbidities, age, nutritional status and behavioural factors in a complex
      assessment process. This article reviews current UK practice in the selection and
      care of patients being assessed for liver transplantation.

PMID- 28489447
TI  - Patient-initiated splintage of a mallet finger injury avoids unnecessary
      complications.

PMID- 28489448
TI  - Immediate postoperative management and complications on the intensive care unit.
AB  - The postoperative management of patients immediately after liver transplantation
      requires knowledge of this complex surgery and the physiology that accompanies
      liver failure. A multidisciplinary approach to the care of these patients is
      essential in order to reduce postoperative complications and preserve function in
      the transplanted organ. By their nature, patients undergoing liver
      transplantation have complicated medical problems before surgery which must be
      borne in mind when managing them after surgery. Haemorrhage, haemodynamic
      instability, acute renal failure, hepatic artery thrombosis and primary graft non
      function are some of the complications that clinicians must be prepared for in
      the first days after transplantation. Pre-empting complications and acting
      rapidly to overt them is likely to have a considerable positive impact in these
      patients.

PMID- 28489449
TI  - Progressive respiratory failure: a rare complication after graded talc
      pleurodesis.

PMID- 28489450
TI  - Anaesthesia for liver transplantation.
AB  - Liver transplantation is a complex procedure that requires a truly
      multidisciplinary team approach with anaesthetic involvement from the outset in
      order to ensure excellent outcomes. Before a patient is placed on the waiting
      list for a liver transplant, a thorough evaluation is undertaken and his/her
      suitability for transplantation discussed in a patient selection committee
      meeting. The perioperative management of patients requiring transplantation can
      be challenging because of the systemic implications of liver disease, approaches
      to surgical technique and the quality of the grafts used; an increase in the use
      of marginal donor organs to meet the organ demand poses its own unique
      difficulties.

PMID- 28489451
TI  - Late presentation of ischaemic monomelic neuropathy after vascular access
      surgery.

PMID- 28489452
TI  - Medicine at war a century ago.

PMID- 28489454
TI  - Acquisition and Transmission of Streptococcus pneumoniae Are Facilitated during
      Rhinovirus Infection in Families with Children.
AB  - RATIONALE: Laboratory and clinical evidence suggests synergy between rhinoviruses
      and Streptococcus pneumoniae in the pathogenesis of respiratory tract infections.
      However, it is unclear whether rhinoviruses promote pneumococcal acquisition and
      transmission. OBJECTIVES: To describe the impact of rhinovirus infection on the
      acquisition and transmission of pneumococci within families with children.
      METHODS: We investigated 29 families with at least two children. The follow-up
      started at the onset of respiratory infectious symptoms in any family member and
      consisted of daily symptom diary and nasal swab samples from each participant
      twice per week for 3 weeks. Swabs were taken by the parents and sent to a study
      clinic by mail. Rhinoviruses were detected by reverse transcription-polymerase
      chain reaction and typed by sequencing. Pneumococci were identified by an antigen
      test and by standard culture methods, serotyping, and whole-genome sequencing.
      The effect of rhinovirus infection on the rates of pneumococcal acquisition and
      within-family transmission was estimated from the observed acquisition events and
      person-times spent uncolonized, using Poisson regression. MEASUREMENTS AND MAIN
      RESULTS: Rhinovirus was detected in 38 subjects (30%) at the onset and in 86
      subjects (67%) during the follow-up. S. pneumoniae was detected on the first day
      in 9 (7%) and during follow-up in 38 (30%) subjects. Children with rhinovirus
      infection had a 4.3-fold rate of pneumococcal acquisition from the community (95%
      confidence interval, 1.1-15.4) and a 14.8-fold rate of within-family transmission
      (95% confidence interval, 3.1-69.6) compared with children without rhinovirus
      infection. CONCLUSIONS: Rhinovirus infection within families facilitates
      acquisition and within-family transmission of S. pneumoniae.

PMID- 28489455
TI  - MicroRNA Profiling in Asthma: Potential Biomarkers and Therapeutic Targets.
AB  - Asthma is a heterogeneous chronic inflammatory disorder in which different
      endotypes contribute to define clinical inflammatory phenotypes. MicroRNAs
      (miRNAs) are a group of minute, endogenous 22-25 nt RNA elements that join to
      particular mRNAs to reduce translation and increase messenger RNA degradation.
      miRNAs operate in post-transcriptional control and regulate physiological and
      pathological processes in several illnesses. The purpose of this work is to
      review and discuss the current knowledge about the function of miRNAs in asthma,
      focusing particularly on their biological properties, pathophysiologic actions,
      and possible use as markers and treatments for asthma.

PMID- 28489453
TI  - Association of Decision-making with Patients' Perceptions of Care and Knowledge
      during Longitudinal Pulmonary Nodule Surveillance.
AB  - RATIONALE: Patient participation in medical decision-making is widely advocated,
      but outcomes are inconsistent. OBJECTIVES: We examined the associations between
      medical decision-making roles, and patients' perceptions of their care and
      knowledge while undergoing pulmonary nodule surveillance. METHODS: The study
      setting was an academically affiliated Veterans Affairs hospital network in which
      121 participants had 319 decision-making encounters. The Control Preferences
      Scale was used to assess patients' decision-making roles. Associations between
      decision-making, including role concordance (i.e., agreement between patients'
      preferred and actual roles), shared decision-making (SDM), and perceptions of
      care and knowledge, were assessed using logistic regression and generalized
      estimating equations. RESULTS: Participants had a preferred role in 98% of
      encounters, and most desired an active role (shared or patient controlled). For
      some encounters (36%), patients did not report their actual decision-making role,
      because they did not know what their role was. Role concordance and SDM occurred
      in 56% and 26% of encounters, respectively. Role concordance was associated with
      greater satisfaction with medical care (adjusted odds ratio [Adj-OR], 5.39; 95%
      confidence interval [CI], 1.68-17.26), higher quality of patient-reported care
      (Adj-OR, 2.86; 95% CI, 1.31-6.27), and more disagreement that care could be
      better (Adj-OR, 2.16; 95% CI, 1.12-4.16). Role concordance was not associated
      with improved pulmonary nodule knowledge with respect to lung cancer risk (Adj
      OR, 1.12; 95% CI, 0.63-2.00) or nodule information received (Adj-OR, 1.13; 95%
      CI, 0.31-4.13). SDM was not associated with perceptions of care or knowledge.
      CONCLUSIONS: Among patients undergoing longitudinal nodule surveillance, a
      majority had a preference for having active roles in decision-making.
      Interestingly, during some encounters, patients did not know what their role was
      or that a decision was being made. Role concordance was associated with greater
      patient-reported satisfaction and quality of medical care, but not with improved
      knowledge. Patient participation in decision-making may influence perceptions of
      care; however, clinicians may need to focus on other communication strategies or
      domains to improve patient knowledge and health outcomes.

PMID- 28489456
TI  - Expired antivenom: good efficacy in a severely envenomed cat bitten by Sistrurus
      miliarius miliarius (Carolina Pigmy Rattlesnake).

PMID- 28489457
TI  - Adverse events associated with a large dose of intravenous lipid emulsion for
      suspected local anesthetic toxicity.
AB  - BACKGROUND: Intravenous lipid emulsion (ILE) has gained favor as a rescue
      treatment for cardiovascular collapse due to intravenous local anesthetic
      overdose, however, goals of ILE therapy are still being defined. We describe a
      case of a girl given 66 mL/kg of 20% lipid emulsion (ILE) in the treatment of
      presumed mepivacaine toxicity. CASE REPORT: An 11-year-old girl weighing 55.6 kg
      developed pallor, rolling back of the eyes, and rhythmic muscle twitching after
      receiving a mandibular nerve block injection with a 1.8 mL ampule of 3%
      mepivacaine. With concern for persistent seizures she was given three 1 mL/kg
      boluses of ILE, followed by an infusion of 0.25 mL/kg/min. The total dose
      ultimately administered was 3670 mL (66 mL/kg) over 7 h. A serum triglyceride
      concentration, drawn 2 h after cessation of ILE infusion, was estimated to be
      16,583 mg/dL (429 mmol/L) after several dilutions; her blood was grossly lipemic.
      Notable signs included hypersomnolence, tachypnea, and tachycardia. Other
      complications included apparent metabolic acidosis (serum bicarbonate of 5
      mmol/L) with hyperlactatemia (lactate 7.0 mmol/L), difficulty with serum
      laboratory interpretation, and a non-contrast brain magnetic resonance imaging
      showing high signal in the dural venous sinuses. The lipemia cleared over three
      days and the patient recovered uneventfully. Case discussion: This case
      demonstrates a unique neurologic and metabolic toxicity associated with ILE given
      as an antidote in a high total dose, and highlights the need for cautious
      antidotal application of lipid emulsion infusions. Until more data is available,
      clinicians are advised to take great care if considering a dose in excess of 12.5
      mL/kg/day, the maximum daily dosage recommended by the U.S. Food and Drug
      Administration for nutritional supplementation. Careful monitoring of total doses
      administered across institutions and hospital wards during transfers is paramount
      to avoid inadvertent overdose of antidotes.

PMID- 28489458
TI  - Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple
      cardiac arrhythmias after ingestion of internet purchased ibogaine.
AB  - BACKGROUND: Ibogaine is an agent that has been evaluated as an unapproved anti
      addictive agent for the management of drug dependence. Sudden cardiac death has
      been described to occur secondary to its use. We describe the clinical effects
      and toxicokinetics of ibogaine and noribogaine in a single patient. For this
      purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine
      plasma-concentrations. We used two compartments with first order absorption. CASE
      DETAILS: The maximum concentration of ibogaine was 1.45 mg/L. Our patient
      developed markedly prolonged QTc interval of 647ms maximum, several multiple
      cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and
      Torsades des Pointes). QTc-prolongation remained present until 12 days after
      ingestion, several days after ibogaine plasma-levels were low, implicating
      clinically relevant noribogaine concentrations long after ibogaine had been
      cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for
      ibogaine, implicating a lower distribution of noribogaine from the peripheral
      compartment into the central compartment compared to ibogaine. CONCLUSIONS: We
      demonstrated a linear relationship between the concentration of the metabolite
      and long duration of action, rather than with parent ibogaine. Therefore, after
      (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due
      to its metabolite.

PMID- 28489459
TI  - Corrigendum.

PMID- 28489460
TI  - A preliminary study in the alterations of mitochondrial respiration in patients
      with carbon monoxide poisoning measured in blood cells.
AB  - OBJECTIVES: Carbon monoxide (CO) is a colorless and odorless gas responsible for
      poisoning mortality and morbidity in the United States. At this time, there is no
      reliable method to predict the severity of poisoning or clinical prognosis
      following CO exposure. Whole blood cells, such as peripheral blood mononuclear
      cells (PBMCs) and platelets, have been explored for their potential use to act as
      sensitive biomarkers for mitochondrial dysfunction which may have a role in CO
      poisoning. DESIGN: The objective of this study was to measure mitochondrial
      respiration using intact cells obtained from patients exposed to CO as a
      potential biomarker for mitochondrial inhibition with results that can be
      obtained in a time frame useful for guiding clinical care. This was a
      prospective, observational pilot study performed from July 2015 to July 2016 at a
      single academic tertiary care center that is the location of the region's only
      multi chamber hyperbaric. MEASUREMENTS: Clinical characteristics, patient
      demographics, mitochondrial respiration and outcomes were recorded. MAIN RESULTS:
      There were 7 patients enrolled with a mean COHb level 26.8 +/- 10 and with a mean
      lactate of 1.1 +/- 0.4 mmol/L. All 7 CO exposures were related to heat generators
      used during winter months with two deaths. There was a positive correlation
      between maximal respiration and COHb levels with both high maximal respiration
      and high spare respiratory capacity correlating with a high COHb level. There was
      a subset of PBMCs (n = 4) that were analyzed for Complex IV (cytochrome c
      oxidase) activity. CONCLUSIONS: In this pilot study, measurements can be
      performed in an appropriate timeline for clinical care with potential to serve as
      a prognostic marker. Further work is necessary to develop high-resolution
      respirometry as a clinical tool for assessing the severity of illness and guiding
      therapy.

PMID- 28489461
TI  - Estimating the impact of adopting the revised United Kingdom acetaminophen
      treatment nomogram in the U.S. population.
AB  - BACKGROUND: Acetaminophen toxicity is common in clinical practice. In recent
      years, several European countries have lowered the treatment threshold, which has
      resulted in increased number of patients being treated at a questionable clinical
      benefit. OBJECTIVE: The primary objective of this study is to estimate the cost
      and associated burden to the United States (U.S.) healthcare system, if such a
      change were adopted in the U.S. METHODS: This study is a retrospective review of
      all patients age 14 years or older who were admitted to one of eight different
      hospitals located throughout the U.S. with acetaminophen exposures during a five
      and a half year span, encompassing from 1 January 2008 to 30 June 2013. Those
      patients who would be treated with the revised nomogram, but not the current
      nomogram were included. The cost of such treatment was extrapolated to a national
      level. RESULTS: 139 subjects were identified who would be treated with the
      revised nomogram, but not the current nomogram. Extrapolating these numbers
      nationally, an additional 4507 (95%CI 3641-8751) Americans would be treated
      annually for acetaminophen toxicity. The cost of lowering the treatment threshold
      is estimated to be $45 million (95%CI 36,400,000-87,500,000) annually.
      CONCLUSIONS: Adopting the revised treatment threshold in the U.S. would result in
      a significant cost, yet provide an unclear clinical benefit.

PMID- 28489462
TI  - Response to Juurlink letter: comment on Shively et al. "Acute salicylate
      poisoning: risk factors for severe outcome".

PMID- 28489463
TI  - Comment on Shively et al. "Acute salicylate poisoning: risk factors for severe
      outcome".

PMID- 28489464
TI  - Results of a randomized controlled pilot trial of intravascular renal denervation
      for management of treatment-resistant hypertension.
AB  - OBJECTIVE: Previous trials of catheter-based renal-artery denervation (RDN) as
      treatment modality in resistant hypertension (rHT) generated unconvincing
      results. In the Investigator-Steered Project on Intravascular Denervation for
      Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we
      optimized selection and management of rHT patients. METHODS: With ethical
      clearance to randomize 18 patients, three Belgian hypertension centers screened
      29 rHT patients on treatment with >=3 drugs, of whom 17 after optimization of
      treatment (age <70 years; systolic/diastolic office blood pressure (BP) >= 140/90
      mm Hg; 24-h BP >=130/80 mm Hg; glomerular filtration rate [eGFR] >= 45
      mL/min/1.73 m2; body mass index <40kg/m2) were randomized and 15 were analyzed 6
      months later, while medical treatment was continued (n = 9) or combined with RDN
      by the EnligHTNTM multi-electrode system (n = 6). RESULTS: The baseline-adjusted
      between-group differences amounted to 19.5/10.4 mm Hg (change in control vs.
      intervention group, +7.6/+2.2 vs. -11.9/-8.2 mm Hg; P = .088) for office BP,
      22.4/13.1 mm Hg (+0.7/+0.3 vs. -21.7/-12.8; mm Hg; P <= .049) for 24-h BP, the
      primary efficacy endpoint, and 2.5 mL/min/1.73 m2 (+1.5 vs. -1.1 mL/min/1.73 m2;
      P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the
      number of prescribed drugs (P <= .036) were lower in RDN patients, but quality of
      life and adherence, captured by questionnaire and urine analysis were similar in
      both groups. Changes in BP and adherence were unrelated. No major complications
      occurred. CONCLUSIONS: The INSPiRED pilot suggests that RDN with the EnligHTNTM
      system is effective and safe and generated insights useful for the design of
      future RDN trials.

PMID- 28489465
TI  - Effects of phototherapy plus physical training on metabolic profile and quality
      of life in postmenopausal women.
AB  - A cluster of metabolic abnormalities are markedly higher among postmenopausal
      women. The present study evaluated the effects of infrared light emitting diode
      (LED) during treadmill training on multiple metabolic markers, body fat, dietary
      habits and quality of life in postmenopausal women. Forty-five postmenopausal
      women aged 50-60 years were randomly assigned to one of three groups, and of
      these, 30 women successfully completed the full study. The three groups were as
      follows: (i) the LED group, which performed treadmill training associated with
      phototherapy (n = 10); (ii) the exercise group, which carried out treadmill
      training only (n = 10); and (iii) the sedentary group, which neither performed
      physical training nor underwent phototherapy (n = 10). Training was performed
      over a period of six months, twice a week for 45 min per session at 85-90% of
      maximal heart rate (HRmax), which was obtained during a progressive exercise
      testing. The average HR and velocity during treadmill training were 144 +/- 9 bpm
      and 5.8 +/- 1.3 km/h for both trained groups. The irradiation parameters were 100
      mW, 39 mW/cm2 and 108 J/cm2 for 45 min. Anthropometric data, skinfolds thickness,
      biochemical exams (lipid profile, glucose and insulin levels), dietary habits and
      quality of life were evaluated. The sum of skinfolds significantly improved in
      the exercise and sedentary groups (p < 0.05). Additionally, there was an
      improvement in lipid profile, particularly, total cholesterol and low-density
      lipoprotein, which reduced significantly for all groups (p ? 0.05). However,
      intake of saturated fats was significantly reduced in the sedentary group only (p
      < 0.05). The quality of life improved in the LED group only, with a significant
      reduction in the total WHQ score (p < 0.05). Physical training with or without
      phototherapy may improve the metabolic profile. In addition, phototherapy
      together with treadmill training prevented an increase in subcutaneous fat and
      facilitated an improved quality of life in postmenopausal women.

PMID- 28489466
TI  - Intrathecal Injection of Gadobutrol: A Tale of Caution.
AB  - In the field of interventional pain medicine a radiocontrast agent is commonly
      used in conjunction with fluoroscopy. Limited work has been published regarding
      the use of gadolium based contrast agents (GBCA) in the intrathecal space. We
      report a case of an intrathecal gadobutrol injection resulting in neurotoxic
      manifestations.A 60-year-old female with a history significant for lumbar post
      laminectomy syndrome and intrathecal drug delivery implantation was admitted for
      lumbar fusion and kyphoplasty. Postoperatively, the patient had escalating pain
      medication requirements. A pump and intrathecal catheter contrast study was
      completed to assess the integrity and proper placement of the intrathecal
      catheter. Due to patient.s allergy to iodinated contrast, the physician requested
      gadolinium contrast dye. Unknown to the staff was that Magnevist had recently
      been replaced with an alternative GBCA, Gadavist (gadobutrol). 2 cc of Gadavist
      was injected. The catheter was determined to be intact and in proper position.
      Less than five minutes after the injection of gadobutrol, the patient reported
      spastic pain of the lower extremities. There is a lack of evidence as it relates
      to the use of GBCA specifically gadobutrol in the intrathecal space. The use of
      gadobutrol in the intrathecal space should be used with caution.

PMID- 28489467
TI  - Use of opioid substitution therapies in the treatment of opioid use disorder:
      results of a UK cost-effectiveness modelling study.
AB  - AIMS: This study investigated the cost-effectiveness of buprenorphine maintenance
      treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid
      substitution therapy (OST) for the treatment of opioid use disorder, from the UK
      National Health Service (NHS)/personal social services (PSS) and societal
      perspectives over 1 year. METHODS: Cost-effectiveness of OST vs no OST was
      evaluated by first replicating and then expanding an existing UK health
      technology assessment model. The expanded model included the impact of OST on
      infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      infection. RESULTS: Versus no OST, incremental cost-effectiveness ratios (ICERs)
      for BMT and MMT were L13,923 and L14,206 per quality-adjusted life year (QALY),
      respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal)
      are considered, there are substantial savings associated with adopting OST; these
      savings are in excess of L14,032 for BMT vs no OST and L17,174 for MMT vs no OST
      over 1 year. This is primarily driven by a reduction in victim costs. OST
      treatment also impacted other aspects of criminality and healthcare resource use.
      LIMITATIONS: The model's 1-year timeframe means long-term costs and benefits, and
      the influence of changes over time are not captured. CONCLUSIONS: OST can be
      considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost
      per QALY well below the UK's willingness-to-pay threshold. There were only small
      differences between BMT and MMT. The availability of two or more cost-effective
      options is beneficial to retaining patients in OST programs. From a societal
      perspective, OST is estimated to save over L14,032 and L17,174 per year for BMT
      and MMT vs no OST, respectively, due to savings in victim costs. Further work is
      required to fully quantify the clinical and health economic impacts of different
      OST formulations and their societal impact over the long-term.

PMID- 28489468
TI  - Best dilution of the best corticosteroid for intralesional injection in the
      treatment of localized alopecia areata in adults.
AB  - PURPOSE: To evaluate and compare the clinical efficacy, dermoscopic results and
      safety of triamcinolone acetonide (TA) and betamethasone dipropionate (BD)
      injections at different concentrations in localized scalp and beard alopecia.
      METHODS: Intralesional injection of BD or TA in three different dilutions; 1/4,
      1/8, 1/12 (BD1, BD2, BD3, TA1, TA2, TA3) and Saline (control) was randomly
      applied to a total of 231 alopecia patches in 83 patients every four weeks in a
      maximum of six sessions until a hair regrowth score of 4 was achieved. The number
      of required sessions, sixth-month hair regrowth scores, treatment success rates
      and dermoscopic data were investigated. RESULTS: The mean number of required
      sessions were similar and significantly lower in BD1 and TA1 being 4.21 +/- 1.12
      and 3.74 +/- 0.99, respectively. Dermoscopic examinations revealed similar
      terminal hair growth rations in Saline (30.3%), BD1 (44.4%) and TA1 (42.9%).
      However, sixth-month hair regrowth scores, overall treatment success rates and
      percentage of terminal hair regrowth were similar in BD1 and TA1. However,
      adverse effects were more common in TA groups (24.3%) than in BD groups (10.6%)
      at the sixth month. CONCLUSIONS: BD 1/4 dilution (1.25 mg/dL) seems best
      corticosteroid for intralesional injection in the treatment of localized alopecia
      areata in adults.

PMID- 28489469
TI  - Significant sE-Selectin levels reduction after 6 months of anti-TNF-alpha therapy
      in non-diabetic patients with moderate-to-severe psoriasis.
AB  - PURPOSE: Psoriasis patients have high risk of atherosclerosis, characterized by
      endothelial dysfunction. We aimed to study the association of the endothelial
      activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E
      selectin and P-selectin with disease activity and severity in psoriasis patients
      treated with anti-TNF-alpha therapy. Also, to evaluate the relationship of
      metabolic syndrome features with these biomarkers and the effect of anti-TNF
      alpha therapy on these molecules. METHODS: Twenty-nine consecutive non-diabetic
      patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF
      alpha-adalimumab therapy were studied. Metabolic and clinical evaluation was
      performed prior to anti-TNF-alpha treatment (time 0) and 6 months later. MCP-1,
      sE-selectin and sP-selectin serum levels were determined by ELISA. RESULTS:
      Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the
      onset of anti-TNF-alpha therapy (p = .05 and .01, respectively). sE-selectin
      positively correlated with pro-inflammatory molecules such as asymmetric
      dimethylarginine, sP-selectin and resistin at baseline and month 6 (p < .05). sE
      selectin levels significantly reduced after 6 months of therapy (p = .0006).
      CONCLUSIONS: Metabolic syndrome features are associated with endothelial
      activation in patients with moderate-to-severe psoriasis. Adalimumab therapy led
      to a reduction in sE-selectin levels, supporting the beneficial effect of anti
      TNF-alpha therapy on mechanisms associated with the development of
      atherosclerosis in psoriasis.

PMID- 28489471
TI  - Effect of the 2011 Revisions to the Field Triage Guidelines on Under- and Over
      Triage Rates for Pediatric Trauma Patients.
AB  - BACKGROUND: In 2011, revised Field Triage Guidelines were released jointly by the
      Centers for Disease Control and Prevention (CDC) and the American College of
      Surgeons - Committee on Trauma (ACS-COT). It is unknown how the modifications
      will affect the number of injured children identified by EMS providers as needing
      transport to a trauma center. OBJECTIVE: To determine the change in under- and
      over-triage rates when the 2011 Field Triage Guidelines are compared to the 2006
      and 1999 versions. METHODS: EMS providers in charge of care for injured children
      (<15 years) transported to pediatric trauma centers in 3 mid-sized cities were
      interviewed immediately after completing transport. Patients were included
      regardless of injury severity. The interview included patient demographics and
      each criterion from the Field Triage Guidelines' physiologic status, anatomic
      injury, and mechanism of injury steps. Included patients were followed through
      hospital discharge. The 1999, 2006, and 2011 Guidelines were each retrospectively
      applied to the collected data. Children were considered to have needed a trauma
      center if they had non-orthopedic surgery within 24 hours, ICU admission, or
      died. Data were analyzed using descriptive statistics. RESULTS: EMS interviews
      were conducted for 5,610 children and outcome data was available for 5,594
      (99.7%). Average age was 7.6 years; 5% of children were identified as needing a
      trauma center using the study outcome. Applying the 1999, 2006, or 2011
      Guidelines to the EMS interview data the over-triage rate was 32.6%, 27.9%, and
      28.0%, respectively. The under-triage rate was 26.5%, 35.1%, and 34.8%,
      respectively. The 2011 Guidelines resulted in an 8.2% (95% CI 0.6-15.9%) absolute
      increase in under-triage and a 4.6% (95% CI 2.8-6.3%) decrease in over-triage
      compared to 1999 Guidelines. CONCLUSION: Use of the Field Triage Guidelines for
      children resulted in an unacceptably high rate of under-triage regardless of the
      version used. Use of the 2011 Guidelines increased under-triage compared to the
      1999 version. Research is needed to determine how to better assist EMS providers
      in identifying children who need the resources of a trauma center.

PMID- 28489472
TI  - Enalapril maleate orally disintegrating tablets: tableting and in vivo evaluation
      in hypertensive rats.
AB  - The aim of this study was to develop orally disintegrating tablets (ODTs) for
      enalapril maleate (EnM) to facilitate its administration to the elderly or other
      patients having dysphagia. Compatibility between EnM and various excipients was
      studied using differential scanning calorimetry. ODTs of EnM were prepared by
      direct compression of EnM mixtures with various superdisintegrants. The tablets
      were evaluated for physical properties including drug content, hardness,
      friability, disintegration time, wetting time, and drug release. The
      antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in
      hypertensive rats and compared with commercial EnM formulation. EnM ODTs had
      satisfactory results in terms of drug content and friability. Tablet wetting and
      disintegration were fast and dependent on the used superdisintegrant where
      croscarmellose showed the fastest wetting and disintegration time of ~7 s. EnM
      release from the tablets was rapid where complete release was obtained in 10-15
      min. Selected EnM ODTs rapidly and efficiently reduced the rat's blood pressure
      to its normal value within 1 h, compared with 4 h for EnM commercial formulation.
      These results confirm that EnM ODTs could find application in the management of
      hypertension in the elderly or other patients having dysphagia.

PMID- 28489470
TI  - Reaction products of hexamethylene diisocyanate vapors with "self" molecules in
      the airways of rabbits exposed via tracheostomy.
AB  - 1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a
      well-recognized cause of occupational asthma. 2. "Self" molecules
      (peptides/proteins) in the lower airways, susceptible to chemical reactivity with
      HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical
      metabolism, but remain poorly characterized. 3. This study employed unique
      approaches to identify and characterize "self" targets of HDI reactivity in the
      lower airways. Anesthetized rabbits free breathed through a tracheostomy tube
      connected to chambers containing either, O2, or O2 plus ~200 ppb HDI vapors.
      Following 60 minutes of exposure, the airways were lavaged and the fluid was
      analyzed by LC-MS and LC-MS/MS. 4. The low-molecular weight (<3 kDa) fraction of
      HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified
      783.26 and 476.18 m/z [M+H]+ ions with high energy collision-induced dissociation
      (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and
      mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction
      of exposed rabbit BAL fluid identified HDI modification of specific lysines in
      uteroglobin (aka clara cell protein) and albumin. 5. In summary, this study
      utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI
      reaction products with "self" molecules in the lower airways.

PMID- 28489473
TI  - Treatment of recalcitrant plantar warts with long-pulsed Nd:YAG laser versus
      cantharidin-podophylline resin-salicylic acid.
AB  - BACKGROUND: Treatment for recalcitrant plantar warts remains a continuing
      challenge as the options for treatment have differing levels of success. long
      pulsed Nd:YAG laser is considered a good treatment modality in resistant plantar
      warts. On the other hand, high cure rates have been reported with a topical
      proprietary formulation consisting of 1% cantharidin, 5% podophyllotoxin, 30%
      salicylic acid. AIM: To compare the efficacy of 1% cantharidin, 20% podophylline
      resin and 30% salicylic acid (CPS) versus long-pulsed Nd:YAG laser in the
      treatment of recalcitrant plantar warts. METHODS: This study included 30 patients
      with single or multiple recalcitrant plantar warts; patients were assigned to two
      groups: the first group included 15 patients with 71 recalcitrant plantar warts
      who were treated by long-pulsed Nd:YAG laser (group I) and the second group
      included 15 patients with 78 recalcitrant plantar warts who received CPS (group
      II). The diagnosis of plantar warts was made by clinical examination. RESULTS:
      Fourteen patients (93%) were completely cleared of their warts with topical CPS,
      while 11 patients (73%) showed complete clearance with long-pulsed Nd:YAG laser
      with statistically significant difference between the two groups. CONCLUSION:
      Topical CPS is safe and efficacious and represents a promising therapeutic
      modality than long-pulsed Nd:YAG laser in the treatment of recalcitrant plantar
      warts.

PMID- 28489474
TI  - Global Burden of Sugar-Related Dental Diseases in 168 Countries and Corresponding
      Health Care Costs.
AB  - Oral diseases such as dental caries, edentulism (tooth loss), periodontal disease
      (PD), and oral cancer currently constitute an increased major public health
      burden across the globe, with significant differences between countries. One of
      the main drivers of caries, edentulism, and PD is the excessive intake of sugars.
      Here, we aimed to quantify the global sugar-related dental health and cost burden
      in the year 2010. This study used a health-econometrical model to calculate the
      disease burden as well as the direct and indirect costs attributable to the
      intake of free sugars (mono- and disaccharides [MDS]). To this end, several
      databases from the Institute for Health Metrics and Evaluation (IHME),
      Organisation for Economic Co-operation and Development (OECD), Food and
      Agriculture Organization (FAO), and World Bank were used. In total, the
      corresponding disease burden in 168 countries and economic burden in 31 OECD
      countries were quantified. In 2010, the consumption of MDS was associated with a
      global dental disease burden of 4.1 million disability-adjusted life years
      (DALYs; 95% uncertainty interval [UI]: 2.1 to 7.4 million DALYs), with 2.7
      million DALYs from MDS-related caries and 1.4 million DALYs from PD. In terms of
      economic costs, MDS-related dental diseases were associated with a global
      financial burden of 172 billion US dollars (USD; 95% UI: 91 to 295 billion USD),
      the largest share of which (151 billion USD) was incurred in OECD countries.
      Overall, 26.3% (95% UI: 13.3% to 47.5%) of the total global oral disease burden
      was attributed to the consumption of MDS. The present study emphasizes the need
      to further address the role of free sugars in oral health and nutrition policy.
      Although the largest share of the economic burden was accounted for by OECD
      countries, emerging economies should address this challenge early on in national
      public health policies if they are to avoid disease and the prospect of increased
      cost burdens.

PMID- 28489475
TI  - Antithrombotic strategies for preventing long-term major adverse cardiovascular
      events in patients with non-valvular atrial fibrillation who undergo percutaneous
      coronary intervention.
AB  - INTRODUCTION: Balancing the risk of recurrent ischemia and bleeding among
      patients with non-valvular atrial fibrillation who undergo percutaneous coronary
      intervention (PCI) is challenging. Postprocedural antithrombotic therapy aims to
      reduce the risk related to coronary artery disease, stent placement, and atrial
      fibrillation, with acceptable risks of bleeding. Areas covered: This review
      summarizes evidence and recommendations related to long-term antithrombotic
      strategies in such patients. An overview of the findings from recent meta
      analyses and select observational studies is provided, and important completed
      and ongoing randomized trials are described in detail. Recommendations pertaining
      to treatment intensity and duration, including the choice of specific
      anticoagulant and antiplatelet agents, are given. Expert opinion: Triple therapy
      (oral anticoagulation with dual antiplatelet therapy) is associated with an
      increased bleeding risk compared with double therapy (oral anticoagulation with a
      single antiplatelet agent), but double therapy does not appear to be associated
      with an increased risk of recurrent ischemia or death. Completed trials make a
      compelling case for double therapy with clopidogrel, not aspirin, when compared
      with full-intensity triple antithrombotic therapy. We believe that double therapy
      with an anticoagulant and clopidogrel should generally be favored instead of
      triple antithrombotic therapy.

PMID- 28489476
TI  - Benefits of Thoracic Epidural Analgesia in Patients Undergoing an Open Posterior
      Component Separation for Abdominal Herniorrhaphy.
AB  - An open posterior component separation (PCS) is a commonly utilized surgical
      approach for repair of complex abdominal wall defects and hernias. Although this
      approach may improve surgical outcomes, significant postoperative pain can be
      expected given the required laparotomy and extensive abdominal wall manipulation.
      Both systemic opioids and thoracic epidural analgesia (TEA) are viable
      postoperative analgesic options, and both are commonly utilized. Although the
      benefits of TEA have been investigated following a variety of surgeries, there is
      a paucity of literature related to its efficacy for this particular surgery. The
      aim of this study was to evaluate the benefits of TEA following open PCS under
      the hypothesis that the incorporation of TEA into the postoperative analgesic
      regimen would hasten bowel recovery. Patients who previously underwent an open
      PCS were identified through an electronic medical record query. A retrospective
      chart review was then performed, and patients who had TEA, either alone or
      combined with systemic opioids, were compared with patients who had only systemic
      opioids. The primary end point was a comparison of the postoperative day (POD) on
      which a full diet was started. Secondarily, time to liquid diet, postsurgical
      length of stay (LOS), intensive care unit (ICU) admission rate, ICU LOS, and the
      rates of several postoperative adverse events were compared. A post hoc analysis
      was also performed, using the same end points, to compare the subgroup of TEA
      patients who avoided systemic opioids with all patients who received systemic
      opioids, whether alone or combined with TEA. One hundred and one patients were
      ultimately included for analysis. Time to full diet was not significantly
      different between patients who had TEA, either with or without systemic opioids,
      and those who received only systemic opioids (TEA 2.6 +/- 1.7 vs. systemic
      opioids 3.1 +/- 2.1 [mean POD +/- SD], P = .21). Additionally, no statistically
      significant differences were found for any secondary outcome. In the post hoc
      analysis, the subgroup of TEA patients who avoided systemic opioids had a
      significantly faster time to bowel recovery when compared with all patients who
      received systemic opioids (2.2 +/- 1.0 vs. 3.2 +/- 2.2, P = .0033). This subgroup
      also had a significantly shorter time to liquid diet and a decreased
      postoperative LOS. In conclusion, for patients undergoing an open PCS, the
      inclusion of TEA in the postoperative analgesic regimen did not by itself hasten
      the return of bowel function. However, when TEA was utilized and systemic opioids
      were avoided, bowel recovery occurred significantly sooner and resulted in a
      shortened hospital LOS.

PMID- 28489477
TI  - Combined Sciatic and Lumbar Plexus Nerve Blocks for the Analgesic Management of
      Hip Arthroscopy Procedures: A Retrospective Review.
AB  - Hip arthroscopy is a minimally invasive alternative to open hip surgery. Despite
      its minimally invasive nature, there can still be significant reported pain
      following these procedures. The impact of combined sciatic and lumbar plexus
      nerve blocks on postoperative pain scores and opioid consumption in patients
      undergoing hip arthroscopy was investigated. A retrospective analysis of 176
      patients revealed that compared with patients with no preoperative peripheral
      nerve block, significant reductions in pain scores to 24 hours were reported and
      decreased opioid consumption during the post anesthesia care unit (PACU) stay was
      recorded; no significant differences in opioid consumption out to 24 hours were
      discovered. A subgroup analysis comparing two approaches to the sciatic nerve
      block in patients receiving the additional lumbar plexus nerve block failed to
      reveal a significant difference for this patient population. We conclude that
      peripheral nerve blockade can be a useful analgesic modality for patients
      undergoing hip arthroscopy.

PMID- 28489478
TI  - Continuous Intravenous Lidocaine Infusion for the Management of Pain Uncontrolled
      by Opioid Medications.
AB  - Limited data exist describing the outcomes of patients receiving continuous
      lidocaine infusions. The objective of this study was to evaluate the effect of
      use of continuous lidocaine infusions for pain management at a community teaching
      hospital. A retrospective chart review was performed that included adult patients
      receiving continuous systemic lidocaine infusions for the treatment of pain.
      Twenty-one patients were included in the analysis. Dosing ranged from 0.25 to 2.8
      mg/kg/h, with a median infusion time of 64 hours. Eight patients (38%)
      experienced a response (>=20% reduction in pain score during the infusion
      compared with prior to the infusion). Among responding patients, there was a
      decrease in pain scores at rest after starting lidocaine (compared with prior to
      lidocaine) (6.5 vs. 3.7, P = .001) that was maintained 24 hours after lidocaine
      discontinuation. There were no differences in pain scores before, during, or
      after lidocaine in the entire study sample. A difference in oral morphine
      equivalent intake was present comparing usage during the infusion vs. day +1 (P =
      .006) and day +2 (P < .001). Similarly, a difference was present comparing
      morphine equivalent usage on day -2 with day +2 (P = .008) and day -1 with day +1
      (P = .006). Continuous infusions of systemic lidocaine appear to be beneficial in
      some patients experiencing uncontrolled pain and may improve pain scores while
      decreasing opioid requirements. Overall beneficial effects of systemic lidocaine
      may last longer than the infusion itself.

PMID- 28489479
TI  - Biologics and dermatology life quality index (DLQI) in the Australasian psoriasis
      population.
AB  - BACKGROUND/OBJECTIVES: Psoriasis is a chronic condition that may require long
      term treatment for disease control. This analysis utilizes data from the
      Australasian Psoriasis Registry with particular attention to the impact of
      biologic therapy on DLQI, and the differences between the biologics in terms of
      DLQI score change. METHODS: A retrospective review of patients enrolled in the
      Australasian Psoriasis Registry from April 2008 to August 2016 was conducted. All
      subjects from the registry that had DLQI and Psoriasis Assessment Severity Index
      (PASI) scores recorded at a baseline time point of treatment commencement, in
      addition to week 12 and 24 post commencement were included in the study. A window
      of +/-3 weeks was permitted at these time points. Multivariate linear regression
      analysis was undertaken to identify significant predictors associated with change
      in DLQI. RESULTS: Significant predictors of reduction in DLQI and PASI score from
      baseline to week 24 include use of adalimumab, infliximab, secukinumab and
      ustekinumab. Other therapies, including etanercept and oral systemic agents did
      not show significant change. Each class of biologic showed significant reductions
      in DLQI score, with IL-12/23 blockade showing the greatest reduction. Significant
      predictors of lack of reduction in DLQI score include a baseline PASI score <16,
      and history of diabetes, alcoholism or uveitis. CONCLUSIONS: Patients with
      moderate to severe chronic plaque psoriasis who are treated with biologics show
      the greatest reduction in DLQI score, compared with other treatments. Australian
      dermatologists are prescribing biologics when patients qualify for them in
      keeping with current guidelines.

PMID- 28489480
TI  - Ponesimod, a selective sphingosine 1-phosphate (S1P1) receptor modulator for
      autoimmune diseases: review of clinical pharmacokinetics and drug disposition.
AB  - 1. Ponesimod, a selective sphingosine 1-phosphate (S1P1) receptor modulator, is
      undergoing clinical development for the treatment of autoimmune diseases
      (multiple sclerosis/psoriasis). 2. Published literature data describing
      pharmacokinetic disposition of ponesimod were collected, reviewed and tabulated.
      3. Across various clinical phase-I studies, ponesimod displayed consistent
      pharmacokinetics - relatively faster absorption peak time (approximately 2.5 h),
      elimination half-life of approximately 30 h and modest accumulation (2- to 2.6
      fold). Ponesimod was extensively metabolized and two major metabolites were ACT
      204426 and ACT-338375. 4. Extensive population pharmacokinetic-pharmacodynamic
      modeling has confirmed the therapeutic dose(s) for ponesimod to achieve the
      balance between safety (primarily heart rate) and efficacy using the maximum
      inhibition of the total lymphocytes as the pharmacodynamic marker. 5. None of the
      covariates (ethnicity, body weight, sex, diseased state including multiple
      sclerosis and psoriasis, food intake, formulation, etc.) examined in population
      pharmacokinetic model influenced the pharmacokinetics of ponesimod from a
      clinical relevance perspective. However, hepatic impairment (moderate/severe but
      not mild), profoundly influenced its disposition; and therefore, would
      necessitate dosage adjustment of ponesimod in clinical therapy. 6. Ponesimod has
      a favorable safety profile and pharmacokinetics, which will allow maximizing its
      ability to inhibit circulating lymphocytes in a given dosing regimen for treating
      autoimmune diseases.

PMID- 28489481
TI  - Efficient Trial Design - FDA Approval of Valbenazine for Tardive Dyskinesia.

PMID- 28489482
TI  - Real world prescription trends of methotrexate for psoriasis in Argentina:
      results of a national survey.
AB  - OBJECTIVE: To describe dermatologists' methotrexate (MTX) prescription trends for
      the treatment of psoriasis, and to identify variables associated with suboptimal
      MTX use. METHODS: Cross-sectional study of dermatologists from Argentina who
      completed a pre-designed survey focussed on MTX prescription characteristics. A
      multiple logistic regression model was used to identify variables independently
      associated with suboptimal MTX use (when less than 12 weeks and less than 15
      mg/week were administrated in patients with monotherapy before discontinuing or
      adding a second drug). RESULTS: Two hundred and twenty-one dermatologists
      participated in the study. Median time of practice in dermatology: 10 (IQR 3-15)
      years. MTX initial dose: 2.5-7.5, 10-15 and 20-30 mg/week in 52%, 41% and 7% of
      the participants, respectively. Suboptimal MTX use was observed in 76% of the
      participants. Thirty per cent of the participants responded that they considered
      MTX to be an ineffective drug. The only variable that was independently
      associated with suboptimal MTX use was the prescriber's personal consideration of
      MTX to be an ineffective drug (OR 2.29; 95%CI 1.05-5.00). CONCLUSION: A wide
      heterogeneity in the prescribing profile of MTX for the treatment of psoriasis
      was observed among Argentinean dermatologists. Suboptimal MTX use was identified
      in the majority of the prescribers.

PMID- 28489483
TI  - A low initial botulinum toxin A treatment response does not predict poor long
      term outcomes in patients with axillary bromhidrosis.
AB  - PURPOSE: For patients with axillary bromhidrosis, it is not clear that whether a
      low response to initial botulinum toxin A (BTX-A) treatment is related to poor
      long-term outcomes. PATIENTS AND METHODS: From August 2011 to March 2016, 31
      patients with primary axillary bromhidrosis were recruited. They had the duration
      of efficacy for less than 4 weeks (median, 3 weeks; range, 1-3 weeks) after the
      first BTX-A injection (50 U per underarm) and were considered to have a low
      response to BTX-A treatment. The second injection with the same dose was
      immediately administered once the symptoms recurred. Subsequent sessions were
      performed with a double dose. RESULTS: The duration of efficacy rose
      significantly to 10 weeks (range, 1-24 weeks) after the second injection (p <
      .01). Twenty-five patients received the third injection. The resultant duration
      further increased to 16 weeks (range, 12-26 weeks). No patients reported adverse
      effects during our follow-up period. CONCLUSIONS: For patients with primary
      axillary bromhidrosis, a low initial BTX-A treatment response does not predict
      poor long-term outcomes. Immediate reinjection with the same dose and subsequent
      sessions with a double dose is a safe strategy and can increase the duration of
      BTX-A therapy.

PMID- 28489484
TI  - Factors affecting the course and severity of adult acne. Observational cohort
      study.
AB  - OBJECTIVE: To identify factors improving symptoms and shortening duration of AA.
      MATERIAL AND METHODS: The observational cohort study was performed in 111
      patients with AA (>25 y.o.) in 2015-2016. Clinical manifestation, previous
      treatments, environmental risk factors and features of juvenile acne affecting AA
      were assessed. RESULTS: The maximum severity of persistent acne was significantly
      lower after 25 years of age, as compared to adolescence (7.2 vs. 6.4; p = .0027).
      The number of acne therapies used in AA was twice as high as in juvenile acne (22
      vs. 11). The severity of AA sufficient to leave scars was significantly lower
      than of juvenile acne (6.0 vs. 7.3; p = .0001) with 22% of patients developing
      scars only in adult life. Patients linked exacerbations to stress exposure (p =
      .09 and <.0001 for those reporting at least one stressor and all patients,
      respectively), finding lifestyle changes the most stressful (p = .046). Those
      using full-coverage foundations received significantly more acne treatments over
      lifetime (5.4 vs. 3.6; p = .0359) and for AA (4.4 vs. 2.8; p = .0043).
      Discontinuation of oral contraceptives or sensitive, erythema-prone skin also
      worsened the symptoms. CONCLUSION: Lifestyle change-related stress, sensitive
      skin, discontinuation of oral contraceptives and using full-coverage foundations
      increase severity of AA.

PMID- 28489486
TI  - Benzathine penicillin G once-every-3-week prophylaxis for recurrent erysipelas a
      retrospective study of 132 patients.
AB  - OBJECTIVE: To evaluate effectivity, safety and patients' adherence to benzathine
      penicillin G (BPG) 1,200,000 units (1.2 MU) once-every-3-week intramuscularly
      prophylaxis for recurrent erysipelas. METHODS: Patients with documented two or
      more erysipelas episodes in last two years who received at least one of 10
      planned doses of BPG 1.2 MU intramuscularly between January 2009 and December
      2015 were analyzed in this retrospective study. Number of recurrences during the
      30-week prophylaxis and in the 30-week follow-up period, frequency of adverse
      events, patients' adherence to the treatment and factors associated with the
      recurrence were analyzed. RESULTS: From 132 patients, 109 (82.6%) finished the 30
      week prophylactic regimen successfully. The incidence of erysipelas was 8 per 100
      patient-years during the prophylactic period and 28 per 100 patient-years in the
      follow-up period (incidence rate ratio = 0.20; 95% CI: 0.05-0.34; p < .01). In
      univariate analysis recurrence was significantly associated only with presence of
      any local risk factor concurrently with obesity (OR 3.40; 95% CI: 1.10-10.50; p <
      .05). CONCLUSION: Benzathine penicillin G 1.2 MU once every 3 weeks is an
      effective and well-tolerated prophylaxis of recurrent erysipelas with good
      patient adherence to the treatment. Further studies to determine the appropriate
      duration of prophylaxis are necessary.

PMID- 28489485
TI  - IGF-1 Mediates EphrinB1 Activation in Regulating Tertiary Dentin Formation.
AB  - Eph receptors belong to a subfamily of receptor tyrosine kinases that are
      activated by membrane-spanning ligands called ephrins. Previously, we
      demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic
      differentiation from dental pulp cells (DPCs) in vitro. The goal of this study
      was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system
      that govern tertiary dentin formation in vitro and in vivo. During tooth
      development, ephrinB1, and EphB2 were expressed in preodontoblast and
      odontoblasts at postnatal day 4. EphrinB1 was continuously expressed in
      odontoblasts and odontoblastic processes until the completion of tooth eruption.
      In addition, ephrinB1 was expressed in odontoblastic processes 2 wk following
      tooth injury without pulp exposure, whereas EphB2 was expressed in the center of
      pulp niches but not odontoblasts. In a model of tooth injury with pulp exposure,
      ephrinB1 was strongly expressed in odontoblasts 4 wk postinjury. In vitro studies
      with human and mouse DPCs treated with calcium hydroxide (CH) or mineral trioxide
      aggregate (MTA) showed an increased expression of insulin-like growth factor 1
      (IGF-1). Experiments using several inhibitors of IGF-1 receptor signaling
      revealed that inhibiting the Ras/Raf-1/MAPK pathway inhibited EphB2 expression,
      and inhibiting the PI3K/Akt/mTOR pathway specifically inhibited ephrinB1 gene
      expression. Tooth injury in mice with odontoblast-specific IGF-1 receptor
      ablation exhibited a reduced tertiary dentin volume, mineral density, and
      ephrinB1 expression 4 wk following injury. We conclude that the IGF-1/ephrinB1
      axis plays significant roles in the early stages of tooth injury. Further
      research is needed to fully understand the potential of targeting ephrinB1 as a
      regenerative pulp therapy.

PMID- 28489487
TI  - What did the March for Science stand for?

PMID- 28489489
TI  - Trajectories of Community-Based Service Use: The Importance of Poverty and Living
      Arrangements.
AB  - This study examined how older adults' living arrangements and poverty status
      affected their use of in-home health, functional, and out-of-home services over
      time. Using eight waves of data from the Korea Welfare Panel Study, we employed a
      logistic mixed-effect model to analyze how poverty and living arrangements affect
      community-based service use. Living-alone older adults and elder-only couples
      were more likely than co-residing households to use services. Elder-only couples,
      when poor, were more likely to use in-home and out-of-home services over time.
      Understanding predictors of community-based service use over time enables
      researchers and policymakers to better understand the process of aging-in-place.

PMID- 28489491
TI  - Risk Factors for Symptoms of Prescription Opioid Misuse: Do Older Adults Differ
      from Younger Adult Patients?
AB  - Limited research is available regarding the health risks associated with opioid
      medication misuse among middle age (50-64 years) and older adults (65 and older).
      Understanding the misuse symptom risk profiles of these populations has potential
      to advance the national opioid epidemic response. A survey was conducted in four
      community pharmacies in southwestern Pennsylvania among adult, non-cancer
      patients filling opioid medications (N = 318) regarding opioid medication misuse
      symptoms and misuse risk factors. Descriptive and multivariate statistical
      analyses compared respondent characteristics, misuse symptoms, and misuse risks
      among those 65 and older, 50 to 64, and those less than 50 years old. Those 65
      and older (Incidence Rate Ratio [IRR] = 2.4, 95% CI = 1.46-3.95) and those 50 to
      64 years (IRR = 1.26, 95% CI = 1.03-1.54) who reported illicit drug use had
      increased rates of misuse symptoms. Those 50-64 with posttraumatic stress
      disorder also had an increased rate of misuse symptoms (IRR = 1.29, 95% CI = 1.08
      1.54). Misuse behaviors of those 65 and older and 50-64 involved shortening time
      between dosages (>=65 = 11.4%, 50-64 = 27.6%), taking higher dosages than
      prescribed (>=65 = 11.4%, 50-64 = 13.6%), and early refills (>=11.8%, 50-64 =
      12.7%). Gerontological social workers must continue to work to understand and
      identify individuals engaged in misuse in order to develop and provide age
      appropriate care.

PMID- 28489488
TI  - Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of
      an NCI Workshop, September 19, 2016.
AB  - A workshop entitled "Radiation-Induced Fibrosis: Mechanisms and Opportunities to
      Mitigate" (held in Rockville, MD, September 19, 2016) was organized by the
      Radiation Research Program and Radiation Oncology Branch of the Center for Cancer
      Research (CCR) of the National Cancer Institute (NCI), to identify critical
      research areas and directions that will advance the understanding of radiation
      induced fibrosis (RIF) and accelerate the development of strategies to mitigate
      or treat it. Experts in radiation biology, radiation oncology and related fields
      met to identify and prioritize the key areas for future research and clinical
      translation. The consensus was that several known and newly identified targets
      can prevent or mitigate RIF in pre-clinical models. Further, basic and
      translational research and focused clinical trials are needed to identify optimal
      agents and strategies for therapeutic use. It was felt that optimally designed
      preclinical models are needed to better study biomarkers that predict for
      development of RIF, as well as to understand when effective therapies need to be
      initiated in relationship to manifestation of injury. Integrating appropriate
      endpoints and defining efficacy in clinical trials testing treatment of RIF were
      felt to be critical to demonstrating efficacy. The objective of this meeting
      report is to (a) highlight the significance of RIF in a global context, (b)
      summarize recent advances in our understanding of mechanisms of RIF,

PMID- 28489492
TI  - "The Action Level"(r).

PMID- 28489490
TI  - The Role of Variability in Motor Learning.
AB  - Trial-to-trial variability in the execution of movements and motor skills is
      ubiquitous and widely considered to be the unwanted consequence of a noisy
      nervous system. However, recent studies have suggested that motor variability may
      also be a feature of how sensorimotor systems operate and learn. This view,
      rooted in reinforcement learning theory, equates motor variability with
      purposeful exploration of motor space that, when coupled with reinforcement, can
      drive motor learning. Here we review studies that explore the relationship
      between motor variability and motor learning in both humans and animal models. We
      discuss neural circuit mechanisms that underlie the generation and regulation of
      motor variability and consider the implications that this work has for our
      understanding of motor learning.

PMID- 28489493
TI  - Characterization of cellulolytic enzyme system of Schizophyllum commune mutant
      and evaluation of its efficiency on biomass hydrolysis.
AB  - Schizophyllum commune is a basidiomycete equipped with an efficient cellulolytic
      enzyme system capable of growth on decaying woods. In this study, production of
      lignocellulose-degrading enzymes from S. commune mutant G-135 (SC-Cel) on various
      cellulosic substrates was examined. The highest cellulase activities including
      CMCase, FPase, and beta-glucosidase were obtained on Avicel-PH101 while a wider
      range of enzymes attacking non-cellulosic polysaccharides and lignin were found
      when grown on alkaline-pretreated biomass. Proteomic analysis of SC-Cel also
      revealed a complex enzyme system comprising seven glycosyl hydrolase families
      with an accessory carbohydrate esterase, polysaccharide lyase, and auxiliary
      redox enzymes. SC-Cel obtained on Avicel-PH101 effectively hydrolyzed all
      agricultural residues with the maximum glucan conversion of 98.0% using corn cobs
      with an enzyme dosage of 5 FPU/g-biomass. The work showed potential of SC-Cel on
      hydrolysis of various herbaceous biomass with enhanced efficiency by addition
      external beta-xylosidase.

PMID- 28489494
TI  - Differences in meanings made according to prolonged grief symptomatology.
AB  - This study investigated differences in specific meanings made following
      bereavement, according to participants' prolonged grief symptomatology. A survey
      of 580 bereaved adults (Mage = 61.6 years, 70.7% female) showed 13 meanings
      predicted symptomatology, with the largest differences between the two lower
      symptomatology groups and the high symptomatology group; the latter was more
      likely to report no meaning. The results provide further support for empirically
      distinct groups within the bereaved population, not only in terms of symptoms,
      etiology, outcomes, courses, and treatment responses, but also in their meanings
      made, and may assist in advancing meaning reconstruction interventions.

PMID- 28489495
TI  - Research with Older Adult Methadone Clients: The Importance of Monitoring Suicide
      Ideation.
AB  - This study reports on the importance of monitoring suicide ideation among older
      adult research participants. A recently completed randomized controlled trial of
      older adults who are current clients in methadone maintenance treatment (MMT)
      served as a case study to elucidate a suicide protocol that was designed to
      account for the potential instances of suicide ideation within the research
      project structure. As the numbers of older adult heroin users increases, this
      study's findings seek to influence research protocols that involve older adults
      with addictions who may be particularly vulnerable to suicide risk due to
      comorbid psychiatric conditions and psychosocial adversities.

PMID- 28489496
TI  - Intergroup Contact: Using Storytelling to Increase Awareness of Lesbian and Gay
      Older Adults in Long-Term Care Settings.
AB  - Due to societally imposed stigmatization, lesbian and gay (LG) older adults fear
      and prolong accessing long-term care (LTC) even though they need LTC at higher
      rates. Interventions that decrease negative attitudes toward LG older adults
      among LTC staff are a first step in addressing this problem. In this study, the
      influence of intergroup contact (IGC) on LTC staff members' attitudes toward LG
      was explored through the use of storytelling as a training mechanism. An embedded
      mixed-method approach was employed to collect and analyze responses of 60 LTC
      staff who participated in a storytelling event. Participants completed pretests,
      posttests, and participated in audio-recorded group discussions. The findings
      showed that storytelling had a significant (p =0.001) and positive effect (d
      =0.57) on participants attitudes toward LG. Qualitative analysis revealed 90
      codes, 13 process codes, and 4 themes: making meaning of stories, seeking
      understanding, application to LTC setting, and debating. When guided by IGC
      theory, storytelling has potential for positively influencing attitudes of LTC
      staff members toward LG older adults. There is a need for longitudinal work to
      further test this model.

PMID- 28489497
TI  - Ecology and Genomic Insights into Plant-Pathogenic and Plant-Nonpathogenic
      Endophytes.
AB  - Plants are colonized on their surfaces and in the rhizosphere and phyllosphere by
      a multitude of different microorganisms and are inhabited internally by
      endophytes. Most endophytes act as commensals without any known effect on their
      plant host, but multiple bacteria and fungi establish a mutualistic relationship
      with plants, and some act as pathogens. The outcome of these plant-microbe
      interactions depends on biotic and abiotic environmental factors and on the
      genotype of the host and the interacting microorganism. In addition, endophytic
      microbiota and the manifold interactions between members, including pathogens,
      have a profound influence on the function of the system plant and the development
      of pathobiomes. In this review, we elaborate on the differences and similarities
      between nonpathogenic and pathogenic endophytes in terms of host plant response,
      colonization strategy, and genome content. We furthermore discuss environmental
      effects and biotic interactions within plant microbiota that influence
      pathogenesis and the pathobiome.

PMID- 28489498
TI  - Fusarium oxysporum and the Fusarium Wilt Syndrome.
AB  - The Fusarium oxysporum species complex (FOSC) comprises a multitude of strains
      that cause vascular wilt diseases of economically important crops throughout the
      world. Although sexual reproduction is unknown in the FOSC, horizontal gene
      transfer may contribute to the observed diversity in pathogenic strains.
      Development of disease in a susceptible crop requires F. oxysporum to advance
      through a series of transitions, beginning with spore germination and culminating
      with establishment of a systemic infection. In principle, each transition
      presents an opportunity to influence the risk of disease. This includes
      modifications of the microbial community in soil, which can affect the ability of
      pathogen propagules to survive, germinate, and infect plant roots. In addition,
      many host attributes, including the composition of root exudates, the structure
      of the root cortex, and the capacity to recognize and respond quickly to invasive
      growth of a pathogen, can impede development of F. oxysporum.

PMID- 28489499
TI  - The Evidential Basis of Decision Making in Plant Disease Management.
AB  - The evidential basis for disease management decision making is provided by data
      relating to risk factors. The decision process involves an assessment of the
      evidence leading to taking (or refraining from) action on the basis of a
      prediction. The primary objective of the decision process is to identify-at the
      time the decision is made-the control action that provides the best predicted end
      of-season outcome, calculated in terms of revenue or another appropriate metric.
      Data relating to disease risk factors may take a variety of forms (e.g.,
      continuous, discrete, categorical) on measurement scales in a variety of units.
      Log10-likelihood ratios provide a principled basis for the accumulation of
      evidence based on such data and allow predictions to be made via Bayesian
      updating of prior probabilities.

PMID- 28489500
TI  - Does One Year of Schooling Improve Children's Cognitive Control and Alter
      Associated Brain Activation?
AB  - The "5-to-7-year shift" refers to the remarkable improvements observed in
      children's cognitive abilities during this age range, particularly in their
      ability to exert control over their attention and behavior-that is, their
      executive functioning. As this shift coincides with school entry, the extent to
      which it is driven by brain maturation or by exposure to formal schooling is
      unclear. In this longitudinal study, we followed 5-year-olds born close to the
      official cutoff date for entry into first grade and compared those who
      subsequently entered first grade that year with those who remained in
      kindergarten, which is more play oriented. The first graders made larger
      improvements in accuracy on an executive-function test over the year than did the
      kindergartners. In an independent functional MRI task, we found that the first
      graders, compared with the kindergartners, exhibited a greater increase in
      activation of right posterior parietal cortex, a region previously implicated in
      sustained attention; increased activation in this region was correlated with the
      improvement in accuracy. These results reveal how the environmental context of
      formal schooling shapes brain mechanisms underlying improved focus on cognitively
      demanding tasks.

PMID- 28489501
TI  - Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and
      Combined Pharmacotherapy.
AB  - OBJECTIVES: The aim of this study was to investigate smoking treatment
      effectiveness and retention in a population with and without mental disorders
      (MD). Participants received cognitive behavioral therapy (CBT) plus nicotine
      patch alone or in combination with other medications (i.e., gum, bupropion, or
      nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care
      Center unit (CAPS), taking into account sociodemographics and smoking profile
      covariates. METHODS: The study involved comparison of treatment success (seven
      day point prevalence abstinence at the end of the treatment) and retention
      (presence of the individual in all of the four medical consultations and six
      group sessions) in two subsamples of patients with MD (n = 267) and without MD (n
      = 397) who were included in a six-week treatment provided by a CAPS from 2007 to
      2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine
      patches, nicotine gums, and bupropion and nortriptyline available, prescribed by
      psychiatrists). RESULTS: Within patients with MD, CBT plus nicotine patch plus
      bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch
      plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with
      treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI
      [0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80,
      95% CI [0.65, 0.99], p = .048) were associated with treatment success. No
      variable was associated with dropout or retention within patients with or without
      MD. CONCLUSION: Our findings support the use of CBT plus nicotine patch plus
      bupropion as well as CBT plus nicotine patch plus gum in samples with high rates
      of medical, psychiatric, and addiction disorders. These findings support those of
      previous studies in the general population. Pharmacological treatment associated
      with group CBT based on cognitive-behavioral concepts and combined with ongoing
      MD treatment seems to be the best option for smoking cessation treatment among
      patients with MD. Units that deal with patients with MD, such as CAPS in Brazil,
      should be encouraged to treat smoking addiction in this population. Future
      studies should investigate retention rates in other samples of patients with MD.

PMID- 28489502
TI  - Advances in cardiac pacing and defibrillation.
AB  - INTRODUCTION: There have been many evolutionary milestones in cardiac implantable
      electronic device (CIED) therapy over the past few decades. These advancements
      have created new  challenges. Right ventricular pacing was the original (late
      1950s) breakthrough, however the risk of pacing induced dyssynchrony has become
      evident. Biventricular pacing provided a viable way to mitigate dyssynchrony, but
      only benefits certain patients (primarily left bundle branch block and QRS
      duration >=150 ms with depressed left ventricular (LV) function). Areas covered:
      Recent advances have made His Bundle pacing an option that may provide
      physiological pacing for a wider patient population. Traditional CIED systems
      utilize transvenous endocardial leads. Unfortunately, leads have been CIEDs'
      weakest link. Lead-related vascular occlusion, infection and malfunction have
      spurred the need for percutaneous lead extraction, and development of
      subcutaneous ICDs and leadless pacing. These options are important for
      individuals with limited vascular access and those at risk for blood borne
      infection. Subcutaneous ICDs have been proposed as optimal for younger patients.
      This recommendation is controversial. Expert commentary: We review recent
      advances including His bundle pacing, percutaneous lead extraction, leadless
      pacing and subcutaneous ICDs as well as their potential use in combination.
      Additional technological evolution promises to make the future of CIEDs exciting.

PMID- 28489503
TI  - Does Prehospital Time Influence Clinical Outcomes in Severe Trauma Patients?: A
      Cross Sectional Study.
AB  - OBJECTIVE: Prehospital time potentially impacts clinical outcomes in severely
      injured trauma patients. The importance of individual components, including scene
      and response time, however, is controversial. Our objective was to determine the
      impact of prehospital times on survival in severely injured patients. METHODS: We
      reviewed injured trauma patients enrolled in a Korean EMS trauma registry during
      2012. Severe trauma patients were defined as having either a "V" or lower in the
      AVPU system, a systolic blood pressure <=90mmHg, or respiratory rate <10 or >29.
      Patients with Injury Severity Scores(ISS) < 9 were excluded. Patients were
      categorized by scene time into 4 groups as follows: <3 minutes, 3-6 minutes, 6-9
      minutes, and >=9 minutes and by prehospital time as follows: <16 minutes, 16-24
      minutes, 24-32 minutes, and >=32 minutes. The primary outcome was in-hospital
      mortality. Multiple linear regression analysis was used to adjust for possible
      confounders. RESULTS: A total of 2,257 eligible patients were analyzed. Scene
      time was <3 minutes in 220 (9.7%), 3-6 in 865 (38.3%), 6-9 in 587 (26.0%), and
      >=9 in 585 (25.9%). In-hospital mortality was 396 (17.5%). Compared to a scene
      time 6 to 9 minutes, mortality was higher as the scene time decreased: odds ratio
      (OR) = 1.3(3 to <6), OR = 1.9(0 to <3). Mortality was slightly decreased as
      prehospital time increased, OR = 1.0(16 to <24), OR = 0.9(24 to <32), OR =
      0.7(>=32). CONCLUSION: Longer prehospital times did not increase mortality in
      severely injured trauma patients in Korea. Furthermore, longer scene times were
      associated with lower mortality.

PMID- 28489504
TI  - Validation of the cell line LS180 as a model for study of the gastrointestinal
      toxicity of mycophenolic acid.
AB  - 1. Gastrointestinal (GI) intolerability is a concern for drugs such as
      mycophenolic acid (MPA) and drug metabolism may play a role. Few in vitro models
      exist that allow for the preclinical evaluation of a potential role of drug
      metabolism in intestinal drug toxicity. Thus, we sought to develop an in vitro
      model based on the human colon adenocarcinoma cell line LS180 to investigate
      MPA's negative effects on intestinal cells. 2. Stability of expression of key
      enzymes of MPA metabolism (UGT1A7, UGT1A9, UGT1A10, UGT2B7, CYP3A4 and CYP3A5),
      transporters (OATP1B1, OATP1B3, OATP2B1, MRP1, MRP2 and MDR1) and the nuclear
      receptor PXR over 12 passages in combination with guanosine supplementation to
      counter MPA's antiproliferative effects (determined by western blot analysis and
      proliferation assays, respectively) was established. 3. Expression of LS180 key
      enzymes remained stable over passages 47-59 and MPA-induced growth inhibition was
      circumvented by exogenous guanosine over a period of three days. MPA was not
      cytotoxic at concentrations up to 250 MUM, a concentration that intestinal cells
      adjacent to the dissolving capsule or tablet are exposed to. 4. We concluded that
      LS180 cells are suitable to study the potential association between MPA
      metabolism and its negative effects on intestinal cells.

PMID- 28489505
TI  - Editorial.

PMID- 28489506
TI  - Prehospital Intubation is Associated with Favorable Outcomes and Lower Mortality
      in ProTECT III.
AB  - OBJECTIVE: Traumatic brain injury (TBI) causes more than 2.5 million emergency
      department visits, hospitalizations, or deaths annually. Prehospital endotracheal
      intubation has been associated with poor outcomes in patients with TBI in several
      retrospective observational studies. We evaluated the relationship between
      prehospital intubation, functional outcomes, and mortality using high quality
      data on clinical practice collected prospectively during a randomized multicenter
      clinical trial. METHODS: ProTECT III was a multicenter randomized, double-blind,
      placebo-controlled trial of early administration of progesterone in 882 patients
      with acute moderate to severe nonpenetrating TBI. Patients were excluded if they
      had an index GCS of 3 and nonreactive pupils, those with withdrawal of life
      support on arrival, and if they had documented prolonged hypotension and/or
      hypoxia. Prehospital intubation was performed as per local clinical protocol in
      each participating EMS system. Models for favorable outcome and mortality
      included prehospital intubation, method of transport, index GCS, age, race, and
      ethnicity as independent variables. Significance was set at alpha = 0.05.
      Favorable outcome was defined by a stratified dichotomy of the GOS-E scores in
      which the definition of favorable outcome depended on the severity of the initial
      injury. RESULTS: Favorable outcome was more frequent in the 349 subjects with
      prehospital intubation (57.3%) than in the other 533 patients (46.0%, p = 0.003).
      Mortality was also lower in the prehospital intubation group (13.8% v. 19.5%, p =
      0.03). Logistic regression analysis of prehospital intubation and mortality,
      adjusted for index GCS, showed that odds of dying for those with prehospital
      intubation were 47% lower than for those that were not intubated (OR = 0.53, 95%
      CI = 0.36-0.78). 279 patients with prehospital intubation were transported by
      air. Modeling transport method and mortality, adjusted for index GCS, showed
      increased odds of dying in those transported by ground compared to those
      transported by air (OR = 2.10, 95% CI = 1.40-3.15). Decreased odds of dying
      trended among those with prehospital intubation adjusted for transport method,
      index GCS score at randomization, age, and race/ethnicity (OR = 0.70, 95% CI =
      0.37-1.31). CONCLUSIONS: In this study that excluded moribund patients,
      prehospital intubation was performed primarily in patients transported by air.
      Prehospital intubation and air medical transport together were associated with
      favorable outcomes and lower mortality. Prehospital intubation was not associated
      with increased morbidity or mortality regardless of transport method or severity
      of injury.

PMID- 28489507
TI  - Development and Validation of the PREMM5 Model for Comprehensive Risk Assessment
      of Lynch Syndrome.
AB  - Purpose Current Lynch syndrome (LS) prediction models quantify the risk to an
      individual of carrying a pathogenic germline mutation in three mismatch repair
      (MMR) genes: MLH1, MSH2, and MSH6. We developed a new prediction model, PREMM5,
      that incorporates the genes PMS2 and EPCAM to provide comprehensive LS risk
      assessment. Patients and Methods PREMM5 was developed to predict the likelihood
      of a mutation in any of the LS genes by using polytomous logistic regression
      analysis of clinical and germline data from 18,734 individuals who were tested
      for all five genes. Predictors of mutation status included sex, age at genetic
      testing, and proband and family cancer histories. Discrimination was evaluated by
      the area under the receiver operating characteristic curve (AUC), and clinical
      impact was determined by decision curve analysis; comparisons were made to the
      existing PREMM1,2,6 model. External validation of PREMM5 was performed in a
      clinic-based cohort of 1,058 patients with colorectal cancer. Results Pathogenic
      mutations were detected in 1,000 (5%) of 18,734 patients in the development
      cohort; mutations included MLH1 (n = 306), MSH2 (n = 354), MSH6 (n = 177), PMS2
      (n = 141), and EPCAM (n = 22). PREMM5 distinguished carriers from noncarriers
      with an AUC of 0.81 (95% CI, 0.79 to 0.82), and performance was similar in the
      validation cohort (AUC, 0.83; 95% CI, 0.75 to 0.92). Prediction was more
      difficult for PMS2 mutations (AUC, 0.64; 95% CI, 0.60 to 0.68) than for other
      genes. Performance characteristics of PREMM5 exceeded those of PREMM1,2,6.
      Decision curve analysis supported germline LS testing for PREMM5 scores >= 2.5%.
      Conclusion PREMM5 provides comprehensive risk estimation of all five LS genes and
      supports LS genetic testing for individuals with scores >= 2.5%. At this
      threshold, PREMM5 provides performance that is superior to the existing
      PREMM1,2,6 model in the identification of carriers of LS, including those with
      weaker phenotypes and individuals unaffected by cancer.

PMID- 28489508
TI  - Tai Chi Chih Compared With Cognitive Behavioral Therapy for the Treatment of
      Insomnia in Survivors of Breast Cancer: A Randomized, Partially Blinded,
      Noninferiority Trial.
AB  - Purpose Cognitive behavioral therapy for insomnia (CBT-I) and Tai Chi Chih (TCC),
      a movement meditation, improve insomnia symptoms. Here, we evaluated whether TCC
      is noninferior to CBT-I for the treatment of insomnia in survivors of breast
      cancer. Patients and Methods This was a randomized, partially blinded,
      noninferiority trial that involved survivors of breast cancer with insomnia who
      were recruited from the Los Angeles community from April 2008 to July 2012. After
      a 2-month phase-in period with repeated baseline assessment, participants were
      randomly assigned to 3 months of CBT-I or TCC and evaluated at months 2, 3 (post
      treatment), 6, and 15 (follow-up). Primary outcome was insomnia treatment
      response-that is, marked clinical improvement of symptoms by the Pittsburgh Sleep
      Quality Index-at 15 months. Secondary outcomes were clinician-assessed remission
      of insomnia; sleep quality; total sleep time, sleep onset latency, sleep
      efficiency, and awake after sleep onset, derived from sleep diaries;
      polysomnography; and symptoms of fatigue, sleepiness, and depression. Results Of
      145 participants who were screened, 90 were randomly assigned (CBT-I: n = 45;
      TCC: n = 45). The proportion of participants who showed insomnia treatment
      response at 15 months was 43.7% and 46.7% in CBT-I and TCC, respectively. Tests
      of noninferiority showed that TCC was noninferior to CBT-I at 15 months ( P =
      .02) and at months 3 ( P = .02) and 6 ( P < .01). For secondary outcomes,
      insomnia remission was 46.2% and 37.9% in CBT-I and TCC, respectively. CBT-I and
      TCC groups showed robust improvements in sleep quality, sleep diary measures, and
      related symptoms (all P < .01), but not polysomnography, with similar
      improvements in both groups. Conclusion CBT-I and TCC produce clinically
      meaningful improvements in insomnia. TCC, a mindful movement meditation, was
      found to be statistically noninferior to CBT-I, the gold standard for behavioral
      treatment of insomnia.

PMID- 28489509
TI  - AKT Inhibition in Solid Tumors With AKT1 Mutations.
AB  - Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low
      prevalence. We performed a multihistology basket study of AZD5363, an ATP
      competitive pan-AKT kinase inhibitor, to determine the preliminary activity of
      AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients
      with advanced solid tumors were treated. The primary end point was safety;
      secondary end points were progression-free survival (PFS) and response according
      to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and
      plasma cell-free DNA (cfDNA) were collected in the majority of patients to
      identify predictive biomarkers of response. Results In patients with AKT1 E17K
      mutant tumors (n = 52) and a median of five lines of prior therapy, the median
      PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3
      months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen
      receptor-positive breast, gynecologic, and other solid tumors, respectively. In
      an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most
      frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type
      allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was
      the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045).
      Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR,
      0.18; P = .004) and response ( P = .025). Responses were not restricted to
      patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade
      >= 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%).
      Conclusion This study provides the first clinical data that AKT1 E17K is a
      therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation
      further conditioned response to AZD5363.

PMID- 28489510
TI  - Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death
      Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study.
AB  - Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to
      evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1
      monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive
      advanced solid tumors. The results from the advanced endometrial cancer cohort
      are reported. Patients and Methods Female patients with locally advanced or
      metastatic PD-L1-positive endometrial cancer who had experienced progression
      after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg
      every 2 weeks for up to 24 months or until progression or unacceptable toxicity.
      Primary efficacy end point was objective response rate by RECIST (version 1.1).
      Secondary end points included safety, duration of response (DOR), progression
      free survival, and overall survival. The data cutoff was February 17, 2016.
      Results Of 75 patients screened, 36 (48.0%) had PD-L1-positive tumors, and 24
      (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least
      two previous lines of therapy for advanced disease. Three patients (13.0%)
      achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was
      not reached. Two patients were still receiving treatment and exhibiting continued
      response at time of data cutoff. Three additional patients (13.0%) achieved
      stable disease, with a median duration of 24.6 weeks. One patient who achieved
      partial response had a polymerase E mutation. Thirteen patients (54.2%)
      experienced treatment-related adverse events (AEs), with fatigue (20.8%),
      pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in >=
      10% of patients. Grade 3 treatment-related AEs were reported in four patients. No
      patient experienced a grade 4 AE, and no patient discontinued treatment because
      of an AE. Conclusion Pembrolizumab demonstrated a favorable safety profile and
      durable antitumor activity in a subgroup of patients with heavily pretreated
      advanced PD-L1-positive endometrial cancer.

PMID- 28489512
TI  - Ethnoracial differences in cannabis use among native-born and foreign-born high
      school students in Ontario.
AB  - The objective of this study was to examine the association of ethnoracial
      background and immigrant status to cannabis use among students in Ontario,
      Canada. Data were derived from the Ontario Student Drug Use and Health Survey, a
      school-based, province-wide survey of students in Grades 7-12. The survey
      utilized a stratified two-stage cluster design. Analyses were based on a pooled
      subsample of 12,527 students in Grades 9-12 during the 2011 and 2013 survey
      cycles and included adjustments for the complex sample design. Results indicate
      that youth who were of South Asian or East/Southeast Asian background were at
      lower odds of cannabis use than those who were White, Black, or mixed-race
      backgrounds. Youth who were of mixed-race background (i.e., White and another
      group) were at higher odds of cannabis use than youth who were of White
      background. The association between ethnoracial background and cannabis use also
      varied for some foreign-born and native-born youth. These findings suggest that
      ethnoracial background should be an important consideration in investigations of
      cannabis use among foreign- relative to native-born youth.

PMID- 28489511
TI  - Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Celecoxib in
      Addition to Standard Chemotherapy for Advanced Non-Small-Cell Lung Cancer With
      Cyclooxygenase-2 Overexpression: CALGB 30801 (Alliance).
AB  - Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with
      worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group
      B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in
      addition to chemotherapy in advanced NSCLC improved progression-free and overall
      survival in patients with moderate to high COX-2 expression by
      immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively
      confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with
      pleural effusion or stage IV according to American Joint Committee on Cancer
      [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed
      for COX-2 by IHC. Patients with COX-2 expression >= 2, performance status of 0 to
      2, and normal organ function were eligible. Chemotherapy was determined by
      histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus
      gemcitabine for squamous histology. Patients were randomly assigned to celecoxib
      (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to
      demonstrate improvement in progression-free survival in patients with COX-2 index
      >= 4 with hazard ratio of 0.645 with approximately 85% power at two-sided
      significance level of .05. Results The study was halted for futility after 312 of
      the planned 322 patients with COX-2 index >= 2 were randomly assigned. There were
      no significant differences between the groups (hazard ratio, 1.046 for COX-2 >=
      4). Subset analyses evaluating histology, chemotherapy regimen, and incremental
      COX-2 expression did not demonstrate any advantage for COX-2 inhibition.
      Elevation of baseline urinary metabolite of prostaglandin E2, indicating
      activation of the COX-2 pathway, was a negative prognostic factor. Values above
      the third quartile may have been a predictive factor. Conclusion COX-2 expression
      by IHC failed to select patients who could benefit from selective COX-2
      inhibition. Urinary metabolite of prostaglandin E2 may be able to identify
      patients who could benefit from COX-2 inhibition.

PMID- 28489514
TI  - Expectations, gender, and norms in migration decision-making.
AB  - This paper argues that expectations - the process of evaluating the chances for
      future attainment of valued goals in the home community (stay decision) vs.
      alternative locations (move decision) - along with family norms about migration
      are major predictors of intention to move, which in turn is a proximate
      determinant of migration behaviour. Utilizing longitudinal data from the 1992 and
      1994 waves of the Thailand National Migration Survey, logistic regression models
      show that a strikingly different set of expectations, household demographic
      indicators, and migrant capital factors were significant determinants of
      migration intentions for men and women; reflecting Thai gender roles. Migration
      intentions, in turn, predicted more permanent, but not temporary, survival
      strategy migration behaviour, while low household income predicted temporary but
      not more permanent migration behaviour. The measure of perceived family migration
      norms was a powerful determinant of migration behaviour, but the size of migrant
      networks was not a statistically significant determinant of either migration
      intentions or behaviour.

PMID- 28489513
TI  - Thyroid Function during Early Life and Dental Development.
AB  - Children with low levels of thyroid hormones (hypothyroidism) have delayed tooth
      eruption, enamel hypoplasia, micrognathia, and anterior open bite, whereas
      children with hyperthyroidism may suffer from accelerated tooth eruption,
      maxillary, and mandibular osteoporosis. However, it is still unknown whether
      thyroid function variations within the normal or subclinical range also have an
      impact on hard dental tissues in healthy children. The objective of this study
      was, therefore, to investigate the association between thyroid function from the
      fetal period until early childhood and dental development at school age. This
      study is embedded in the Generation R Study, a population-based cohort study
      established in Rotterdam, the Netherlands. Maternal thyroid function (thyroid
      stimulating hormone [TSH], free thyroxine [FT4], and thyroid peroxidase antibody
      [TPOAb] concentrations) was measured during early pregnancy, and thyroid function
      of the offspring (TSH and FT4) was measured in cord blood at birth and in early
      childhood (6 y). Dental development was assessed from panoramic radiographs of
      children of school-going age (9 y). In total, 2,387 to 2,706 subjects were
      available for the multivariable linear regression analysis, depending on the
      point in time of thyroid function measurement. There was an inverse association
      between cord blood and early childhood TSH concentrations with dental
      development, with a -0.06 lower standard deviation (SD) per 1 mU/L of TSH (95%
      confidence interval [CI], -0.11 to -0.01) and a -0.06 lower SD per 1 mU/L of TSH
      (95% CI, -0.11 to 0.00), respectively. There was no association between the
      maternal thyroid function during pregnancy and the dental development score of
      the child. However, TPOAb-positive mothers had children with a -0.20 SD (adjusted
      95% CI, -0.35 to -0.04) lower dental development score compared with TPOAb
      negative mothers. The findings of this study suggest that the thyroid hormone is
      involved in the maturation of teeth from the early stages of life onward.

PMID- 28489516
TI  - A reply to J. Antonio Ortega Osona and H-P Kohler.

PMID- 28489517
TI  - Forgone income and motherhood: What do recent British data tell u?
AB  - Children affect women s opportunities in the labour markets of most advanced
      countries in three ways: an immediate effect on employment, and effects on longer
      term earning power and pension coverage. This paper quantifies these impacts on
      women s lifetime income for hypothetical illustrative British cases. New results,
      based on data collected during the 1990s, are compared with estimates from 1980.
      Although childrearing and employment have increasingly been combined over the
      period, the estimated loss of gross earnings associated with motherhood remains
      substantial. It still amounts to around half potential earnings post childbirth
      for less qualified sections of the British female labour force, but has become
      smaller for highly qualified women. The paper examines the effect of the
      tax/benefit system on the costs, and makes some assumptions about the
      distribution of net costs between mothers and fathers. It also shows how far
      motherhood jeopardizes financial security in old age, particularly for the least
      qualified.

PMID- 28489518
TI  - A comment on "Recent European fertility patterns: Fitting curves to distorted
      distributions" by T. Chandola, D. A. Coleman and R. W. Hiorns.

PMID- 28489519
TI  - Validity and reliability of the Disabilities of Arm, Shoulder, and Hand scale in
      dental students: A transnational study.
AB  - This study aimed to evaluate the validity and reliability of the Disabilities of
      Arm, Shoulder, and Hand (DASH) scale in Brazilian and American dental students
      and assess the influence of demographic variables on disability in them. A cross
      sectional observational study was conducted with a nonprobabilistic sample. The
      sample was composed of students of both genders from the School of Dentistry of
      Araraquara, State University of Sao Paulo (UNESP) (n = 288), and students from
      Stony Brook University, New York, NY, USA (n = 149). The disabilities of the
      upper limbs were estimated using the DASH scale. The samples were characterized
      by collecting information on gender, academic year, and sports and work
      activities. The refined bifactorial model presented goodness-of-fit indices for
      both countries. There was a significant effect of the variables gender and
      academic year for the Brazilian sample and the variable sports practices for the
      American sample. The refined bifactorial model was valid and reliable for the
      Brazilian and American populations. In this model, the removal of item 17 for the
      Brazilian sample and items 3, 13, and 23 for the American sample was necessary.
      Demographic variables such as gender, academic year, and sports practice
      contributed significantly to the level of disability in the study populations.

PMID- 28489520
TI  - Intergenerational exchanges in Vietnam: Family size, sex composition, and the
      location of children.

PMID- 28489521
TI  - Social inequalities in cancer survival.
AB  - Social differentials in survival from twelve common types of cancer were assessed
      by estimating a mixed additive-multiplicative hazard model on the basis of
      individual register and census data for the whole Norwegian population. The
      excess all-cause mortality among cancer patients compared with similar persons
      without a cancer diagnosis was significantly related to education, occupation,
      and income. Excess mortality was, on the whole, about 15 per cent lower for men
      or women who had completed a post-secondary education than for those with only
      compulsory schooling, taking into account age, period and registered differences
      in tumour characteristics and stage at the time of diagnosis. The data do not
      provide clear indications of whether differences in host factors, such as co
      morbidities and immune functions, or differences in treatment and care are
      primarily responsible for these inequalities in cancer survival.

PMID- 28489523
TI  - Dynamics of marriage change in Chinese rural society in transition: A study of a
      northern Chinese village.
AB  - This analysis uses data from an intensive village study to investigate the
      impacts of institutional reforms on marriage in rural China. The study finds that
      age at marriage has been declining significantly both for men and women. The
      'exchange marriage' and the 'mercenary marriage' have re-emerged. An increasing
      proportion of marriages occur between men and women in nearby villages, though
      there is no significant increase in village endogamy. Both bride price and dowry
      have increased significantly, and the ratio of value of dowry to bride price has
      undergone a dramatic equalization. The young, including young women, have much
      more decision making power regarding their marriages. Changes in marriage are the
      consequences of both change in the socio-economic environment brought about by
      deliberate rural reforms, and strategic or tactical responses of rural Chinese to
      the rapidly changing context in which they live and work.

PMID- 28489524
TI  - Gender in population research: Confusing implications for health policy.
AB  - In this paper I discuss some of the health policy implications of an increasing
      trend in population research and in its interpretation and presentation - a trend
      to 'political correctness' - defined not in the popular, often derogatory, sense,
      but as an ideological commitment to certain principles. For one of these
      commitments, that to the notion of gender equality, greater strength and
      legitimacy is today commonly sought by tying it to other less controversial goals
      such as that of better health. But straining for connections between gender
      equality and positive health outcomes often unduly constrains the research
      question, the research methods, and the interpretation of the research. When
      health policy seeks guidance from this research, it can receive signals which are
      too often incomplete, silent on the many trade-offs of specific policy measures,
      and, ultimately, perhaps even detrimental to the very goals of gender equity and
      social justice from which they are derived. Examples of all these possibilities
      are discussed.

PMID- 28489525
TI  - The evolution of cohabitation in Britain, 1960-95.
AB  - The recent rise in cohabitation in Britain is analysed using data from large
      scale surveys. There are major inconsistencies between different sources, and
      retrospective estimates are higher than values reported at the time.
      Retrospective data show markedly smaller numbers of cohabitation events just
      before survey date. I discuss reasons for discrepancies and conclude that no
      objective measure of cohabitation exists and that comparison of different types
      of data requires care. I combine the data to produce a much larger data set than
      hitherto available. Although cohabitation prevalence increased substantially
      during the 1970s and 1980s, there was little change in such characteristics as
      duration of cohabitation, ages of those cohabiting, and whether it occurred
      before first marriage or ended in marriage or breakdown. However, since the late
      1980s, the average length of cohabitation has increased markedly, which may
      indicate a qualitative change in the nature of cohabitation in Britain.

PMID- 28489526
TI  - Trends in cohabitation and implications for children s family contexts in the
      United States.
AB  - This paper documents increasing cohabitation in the United States, and the
      implications of this trend for the family lives of children. The stability of
      marriage-like relationships (including marriage and cohabitation) has decreased
      despite a constant divorce rate. Children increasingly live in cohabiting
      families either as a result of being born to cohabiting parents or of their
      mother s entry into a cohabiting union. The proportion of births to unmarried
      women born into cohabiting families increased from 29 to 39 per cent in the
      period 1980-84 to 1990-94, accounting for almost all of the increase in unmarried
      childbearing. As a consequence, about two-fifths of all children spend some time
      in a cohabiting family, and the greater instability of families begun by
      cohabitation means that children are also more likely to experience family
      disruption. Estimates from multi-state life tables indicate the extent to which
      the family lives of children are spent increasingly in cohabiting families and
      decreasingly in married families.

PMID- 28489527
TI  - Role of Glucomannans in Immunology.
AB  - Glucomannans play a much broader role in human health then providing dietary
      fibre. They are biologically active molecules and can when added to the body
      imitate innate molecules found in different organs including surface
      carbohydrates on cells. This review considers the immunological role of exogenous
      glucomannans within animals and man. This article is open to POST-PUBLICATION
      REVIEW. Registered readers (see "For Readers") may comment by clicking on
      ABSTRACT on the issue's contents page.

PMID- 28489529
TI  - Modeling Touch and Palpation Using Autoregressive Models.
AB  - OBJECTIVE: The human haptic system uses a set of reproducible and subconscious
      hand maneuvers to identify objects. Similar subconscious maneuvers are used
      during medical palpation for screening and diagnosis. The goal of this work was
      to develop a mathematical model that can be used to describe medical palpation
      techniques. METHODS: Palpation data were measured using a two-dimensional array
      of force sensors. A novel algorithm for estimating the hand position from force
      data was developed. The hand position data were then modeled using multivariate
      autoregressive models. Analysis of these models provided palpation direction and
      frequency as well as palpation type. The models were tested and validated using
      three different data sets: simulated data, a simplified experiment in which
      participant followed a known pattern, and breast simulator palpation data.
      RESULTS: Simulated data showed that the minimal error in estimating palpation
      direction and frequency is achieved when the sampling frequency is five to ten
      times the palpation frequency. The classification accuracy was for the simplified
      experiment and for the breast simulator data. CONCLUSION: Proper palpation is one
      of the vital components of many hands-on clinical examinations. In this study, an
      algorithm for characterizing medical palpation was developed. The algorithm
      measured palpation frequency and direction for the first time and provided
      classification of palpation type. SIGNIFICANCE: These newly developed models can
      be used for quantifying and assessing clinical technique, and consequently, lead
      to improved performance in palpation-based exams. Furthermore, they provide a
      general tool for the study of human haptics.

PMID- 28489528
TI  - Reciprocal synapses between mushroom body and dopamine neurons form a positive
      feedback loop required for learning.
AB  - Current thought envisions dopamine neurons conveying the reinforcing effect of
      the unconditioned stimulus during associative learning to the axons of Drosophila
      mushroom body Kenyon cells for normal olfactory learning. Here, we show using
      functional GFP reconstitution experiments that Kenyon cells and dopamine neurons
      from axoaxonic reciprocal synapses. The dopamine neurons receive cholinergic
      input via nicotinic acetylcholine receptors from the Kenyon cells; knocking down
      these receptors impairs olfactory learning revealing the importance of these
      receptors at the synapse. Blocking the synaptic output of Kenyon cells during
      olfactory conditioning reduces presynaptic calcium transients in dopamine
      neurons, a finding consistent with reciprocal communication. Moreover, silencing
      Kenyon cells decreases the normal chronic activity of the dopamine neurons. Our
      results reveal a new and critical role for positive feedback onto dopamine
      neurons through reciprocal connections with Kenyon cells for normal olfactory
      learning.

PMID- 28489530
TI  - Real-Time Three-Dimensional Microwave Monitoring of Interstitial Thermal Therapy.
AB  - We report a method for real-time three-dimensional monitoring of thermal therapy
      through the use of noncontact microwave imaging. This method is predicated on
      using microwaves to image changes in the dielectric properties of tissue with
      changing temperature. Instead of the precomputed linear Born approximation that
      was used in prior work to speed up the frame-to-frame inversions, here we use the
      nonlinear distorted Born iterative method (DBIM) to solve the electric volume
      integral equation (VIE) to image the temperature change. This is made possible by
      using a recently developed graphic processing unit accelerated conformal finite
      difference time domain method to solve the forward problem and update the
      electric field in the monitored region in each DBIM iteration. Compared to our
      previous work, this approach provides a far superior approximation of the
      electric field within the VIE, and thus yields a more accurate reconstruction of
      tissue temperature change. The proposed method is validated using a realistic
      numerical model of interstitial thermal therapy for a deep-seated brain lesion.
      With the new DBIM, we reduced the average estimation error of the mean
      temperature within the region of interest from 2.5 to 1.0 for the noise-free
      case, and from 2.9 to 1.7 for the 2% background noise case.

PMID- 28489531
TI  - 3D Object Localisation from Multi-View Image Detections.
AB  - In this work we present a novel approach to recover objects 3D position and
      occupancy in a generic scene using only 2D object detections from multiple view
      images. The method reformulates the problem as the estimation of a quadric
      (ellipsoid) in 3D given a set of 2D ellipses fitted to the object detection
      bounding boxes in multiple views. We show that a closed-form solution exists in
      the dual-space using a minimum of three views while a solution with two views is
      possible through the use of non-linear optimisation and object constraints on the
      size of the object shape. In order to make the solution robust toward inaccurate
      bounding boxes, a likely occurrence in object detection methods, we introduce a
      data preconditioning technique and a non-linear refinement of the closed form
      solution based on implicit subspace constraints. Results on synthetic tests and
      on different real datasets, involving challenging scenarios, demonstrate the
      applicability and potential of our method in several realistic scenarios.

PMID- 28489532
TI  - Video Super-Resolution via Bidirectional Recurrent Convolutional Networks.
AB  - Super resolving a low-resolution video, namely video super-resolution (SR), is
      usually handled by either single-image SR or multi-frame SR. Single-Image SR
      deals with each video frame independently, and ignores intrinsic temporal
      dependency of video frames which actually plays a very important role in video
      SR. Multi-Frame SR generally extracts motion information, e.g., optical flow, to
      model the temporal dependency, but often shows high computational cost.
      Considering that recurrent neural networks (RNNs) can model long-term temporal
      dependency of video sequences well, we propose a fully convolutional RNN named
      bidirectional recurrent convolutional network for efficient multi-frame SR.
      Different from vanilla RNNs, 1) the commonly-used full feedforward and recurrent
      connections are replaced with weight-sharing convolutional connections. So they
      can greatly reduce the large number of network parameters and well model the
      temporal dependency in a finer level, i.e., patch-based rather than frame-based,
      and 2) connections from input layers at previous timesteps to the current hidden
      layer are added by 3D feedforward convolutions, which aim to capture discriminate
      spatio-temporal patterns for short-term fast-varying motions in local adjacent
      frames. Due to the cheap convolutional operations, our model has a low
      computational complexity and runs orders of magnitude faster than other multi
      frame SR methods. With the powerful temporal dependency modeling, our model can
      super resolve videos with complex motions and achieve well performance.

PMID- 28489533
TI  - Shakeout: A New Approach to Regularized Deep Neural Network Training.
AB  - Recent years have witnessed the success of deep neural networks in dealing with a
      plenty of practical problems. Dropout has played an essential role in many
      successful deep neural networks, by inducing regularization in the model
      training. In this paper, we present a new regularized training approach:
      Shakeout. Instead of randomly discarding units as Dropout does at the training
      stage, Shakeout randomly chooses to enhance or reverse each unit's contribution
      to the next layer. This minor modification of Dropout has the statistical trait:
      the regularizer induced by Shakeout adaptively combines , and regularization
      terms. Our classification experiments with representative deep architectures on
      image datasets MNIST, CIFAR-10 and ImageNet show that Shakeout deals with over
      fitting effectively and outperforms Dropout. We empirically demonstrate that
      Shakeout leads to sparser weights under both unsupervised and supervised
      settings. Shakeout also leads to the grouping effect of the input units in a
      layer. Considering the weights in reflecting the importance of connections,
      Shakeout is superior to Dropout, which is valuable for the deep model
      compression. Moreover, we demonstrate that Shakeout can effectively reduce the
      instability of the training process of the deep architecture.

PMID- 28489534
TI  - Dynamic 2-D/3-D Rigid Registration Framework Using Point-To-Plane Correspondence
      Model.
AB  - In image-guided interventional procedures, live 2-D X-ray images can be augmented
      with preoperative 3-D computed tomography or MRI images to provide planning
      landmarks and enhanced spatial perception. An accurate alignment between the 3-D
      and 2-D images is a prerequisite for fusion applications. This paper presents a
      dynamic rigid 2-D/3-D registration framework, which measures the local 3-D-to-2-D
      misalignment and efficiently constrains the update of both planar and non-planar
      3-D rigid transformations using a novel point-to-plane correspondence model. In
      the simulation evaluation, the proposed method achieved a mean 3-D accuracy of
      0.07 mm for the head phantom and 0.05 mm for the thorax phantom using single-view
      X-ray images. In the evaluation on dynamic motion compensation, our method
      significantly increases the accuracy comparing with the baseline method. The
      proposed method is also evaluated on a publicly-available clinical angiogram data
      set with "gold-standard" registrations. The proposed method achieved a mean 3-D
      accuracy below 0.8 mm and a mean 2-D accuracy below 0.3 mm using single-view X
      ray images. It outperformed the state-of-the-art methods in both accuracy and
      robustness in single-view registration. The proposed method is intuitive,
      generic, and suitable for both initial and dynamic registration scenarios.

PMID- 28489535
TI  - Lead-Free Multilayer Piezoceramic Composites: Effect of Cosintering on
      Electromechanical Properties.
AB  - The macroscopic electromechanical behavior of lead-free multilayer composites was
      characterized from room temperature to 150  degrees C. The polar seed component
      consisted of a nonergodic relaxor (Bi1/2Na1/2)TiO3-7BaTiO3, with an electric
      field-induced long-range ferroelectric order, whereas the nonpolar matrix was an
      ergodic relaxor Bi0.5(Na0.75K0.25)0.5 TiO3-6BiAlO3 that undergoes a reversible
      electric-field-induced macroscopic nonpolar-to-polar transition. Microstructural
      evidence of the effects of cosintering are demonstrated through examination of
      grain size, interdiffusion, and pore structure. By manipulating the sintering
      interactions between the two constituents, namely, diffusion paths and residual
      stresses, both internal mechanical and electrical fields, as well as
      compositional gradients can be used to enhance the unipolar strain over that
      expected by a rule of mixtures approximation, thereby improving the properties
      needed for application of such materials to actuator systems.

PMID- 28489537
TI  - Real-Time Video Stylization Using Object Flows.
AB  - We present a real-time video stylization system and demonstrate a variety of
      painterly styles rendered on real video inputs. The key technical contribution
      lies on the object flow, which is robust to inaccurate optical flow, unknown
      object transformation and partial occlusion as well. Since object flows relate
      regions of the same object across frames, shower-door effect can be effectively
      reduced where painterly strokes and textures are rendered on video objects. The
      construction of object flows is performed in real time and automatically after
      applying metric learning. To reduce temporal flickering, we extend the bilateral
      filtering into motion bilateral filtering. We propose quantitative metrics to
      measure the temporal coherence on structures and textures of our stylized videos,
      and perform extensive experiments to compare our stylized results with baseline
      systems and prior works specializing in watercolor and abstraction.

PMID- 28489538
TI  - A Perception-Driven Approach to Supervised Dimensionality Reduction for
      Visualization.
AB  - Dimensionality reduction (DR) is a common strategy for visual analysis of labeled
      high-dimensional data. Low-dimensional representations of the data help, for
      instance, to explore the class separability and the spatial distribution of the
      data. Widely-used unsupervised DR methods like PCA do not aim to maximize the
      class separation, while supervised DR methods like LDA often assume certain
      spatial distributions and do not take perceptual capabilities of humans into
      account. These issues make them ineffective for complicated class structures.
      Towards filling this gap, we present a perception-driven linear dimensionality
      reduction approach that maximizes the perceived class separation in projections.
      Our approach builds on recent developments in perception-based separation
      measures that have achieved good results in imitating human perception. We extend
      these measures to be density-aware and incorporate them into a customized
      simulated annealing algorithm, which can rapidly generate a near optimal DR
      projection. We demonstrate the effectiveness of our approach by comparing it to
      state-of-the-art DR methods on 93 datasets, using both quantitative measure and
      human judgments. We also provide case studies with class-imbalanced and unlabeled
      data.

PMID- 28489536
TI  - Dual-Frequency Piezoelectric Endoscopic Transducer for Imaging Vascular Invasion
      in Pancreatic Cancer.
AB  - Cancers of the pancreas have the poorest prognosis among all cancers, as many
      tumors are not detected until surgery is no longer a viable option. Surgical
      viability is typically determined via endoscopic ultrasound imaging. However,
      many patients who may be eligible for resection are not offered surgery due to
      diagnostic challenges in determining vascular or lymphatic invasion. In this
      paper, we describe the development of a dual-frequency piezoelectric transducer
      for rotational endoscopic imaging designed to transmit at 4 MHz and receive at 20
      MHz in order to image microbubble-specific superharmonic signals. Imaging
      performance is assessed in a tissue-mimicking phantom at depths from 1 cm
      [contrast-to-tissue ratio (CTR) = 21.6 dB] to 2.5 cm (CTR = 11.4 dB), in ex vivo
      porcine vessels, and in vivo in a rodent. The prototyped 1.1-mm aperture
      transducer demonstrates contrast-specific imaging of microbubbles in a 200-
      [Formula: see text]-diameter tube through the wall of a 1-cm-diameter porcine
      artery, suggesting such a device may enable direct visualization of small vessels
      from within the lumen of larger vessels such as the portal vein or superior
      mesenteric vein.

PMID- 28489539
TI  - Task-Independent Mental Workload Classification Based Upon Common Multiband EEG
      Cortical Connectivity.
AB  - Efficient classification of mental workload, an important issue in neuroscience,
      is limited, so far to single task, while cross-task classification remains a
      challenge. Furthermore, network approaches have emerged as a promising direction
      for studying the complex organization of the brain, enabling easier
      interpretation of various mental states. In this paper, using two mental tasks (N
      back and mental arithmetic), we present a framework for cross- as well as within
      task workload discrimination by utilizing multiband electroencephalography (EEG)
      cortical brain connectivity. In detail, we constructed functional networks in EEG
      source space in different frequency bands and considering the individual
      functional connections as classification features, we identified salient feature
      subsets based on a sequential feature selection algorithm. These connectivity
      subsets were able to provide accuracy of 87% for cross-task, 88% for N-back task,
      and 86% for mental arithmetic task. In conclusion, our method achieved to detect
      a small number of discriminative interactions among brain areas, leading to high
      accuracy in both within-task and cross-task classifications. In addition, the
      identified functional connectivity features, the majority of which were detected
      in frontal areas in theta and beta frequency bands, helped delineate the shared
      as well as the distinct neural mechanisms of the two mental tasks.

PMID- 28489540
TI  - Nonlinear Frequency-Domain Analysis of the Transformation of Cortical Inputs by a
      Motoneuron Pool-Muscle Complex.
AB  - Corticomotor coherence in the beta and/or gamma bands has been described in
      different motor tasks, but the role of descending brain oscillations on force
      control has been elusive. Large-scale computational models of a motoneuron pool
      and the muscle it innervates have been used as tools to advance the knowledge of
      how neural elements may influence force control. Here, we present a frequency
      domain analysis of a NARX model fitted to a large-scale neuromuscular model by
      the means of generalized frequency response functions (GFRF). The results of such
      procedures indicated that the computational neuromuscular model was capable of
      transforming an oscillatory synaptic input (e.g., at 20 Hz) into a constant mean
      muscle force output. The nonlinearity uncovered by the GFRFs of the NARX model
      was responsible for the demodulation of an oscillatory input (e.g., a beta band
      oscillation coming from the brain and forming the input to the motoneuron pool).
      This suggests a manner by which brain rhythms descending as command signals to
      the spinal cord and acting on a motoneuron pool can regulate a maintained muscle
      force. In addition to the scientific aspects of these results, they provide new
      interpretations that may further neural engineering applications associated with
      quantitative neurological diagnoses and robotic systems for artificial limbs.

PMID- 28489542
TI  - A Grouping Particle Swarm Optimizer with Personal-Best-Position Guidance for
      Large Scale Optimization.
AB  - Particle Swarm Optimization (PSO) is a popular algorithm which is widely
      investigated and well implemented in many areas. However, the canonical PSO does
      not perform well in population diversity maintenance so that usually leads to a
      premature convergence or local optima. To address this issue, we propose a
      variant of PSO named Grouping PSO with Personal- Best-Position (Pbest) Guidance
      (GPSO-PG) which maintains the population diversity by preserving the diversity of
      exemplars. On one hand, we adopt uniform random allocation strategy to assign
      particles into different groups and in each group the losers will learn from the
      winner. On the other hand, we employ personal historical best position of each
      particle in social learning rather than the current global best particle. In this
      way, the exemplars diversity increases and the effect from the global best
      particle is eliminated. We test the proposed algorithm to the benchmarks in CEC
      2008 and CEC 2010, which concern the large scale optimization problems (LSOPs).
      By comparing several current peer algorithms, GPSO-PG exhibits a competitive
      performance to maintain population diversity and obtains a satisfactory
      performance to the problems.

PMID- 28489543
TI  - Integrating Multiple Heterogeneous Networks for Novel LncRNA-disease Association
      Inference.
AB  - Accumulating experimental evidence has indicated that long non-coding RNAs
      (lncRNAs) are critical for the regulation of cellular biological processes
      implicated in many human diseases. However, only relatively few experimentally
      supported lncRNA-disease associations have been reported. Developing effective
      computational methods to infer lncRNA-disease associations is becoming
      increasingly important. Current network-based algorithms typically use a network
      representation to identify novel associations between lncRNAs and diseases. But
      these methods are concentrated on specific entities of interest (lncRNAs and
      diseases) and they do not allow to consider networks with more than two types of
      entities. Considering the limitations in previous computational methods, we
      develop a new global network-based framework, LncRDNetFlow, to prioritize disease
      related lncRNAs. LncRDNetFlow utilizes a flow propagation algorithm to integrate
      multiple networks based on a variety of biological information including lncRNA
      similarity, protein-protein interactions, disease similarity and the associations
      between them to infer lncRNA-disease associations. We show that LncRDNetFlow
      performs significantly better than the existing stat-ofthe- art approaches in
      cross-validation. To further validate the reproducibility of the performance, we
      use the proposed method to identify the related lncRNAs for ovarian cancer,
      glioma and cervical cancer. The results are encouraging. Many predicted lncRNAs
      in the top list have been verified by the biological studies.

PMID- 28489541
TI  - The Effect of Prosthesis Use on Hand Mental Rotation After Unilateral Upper-Limb
      Amputation.
AB  - Amputation of a limb induces changes in the so-called body schema, which might be
      influenced by the use of prosthetic devices. Changes in the body representation
      associated with prosthesis use could be investigated using a hand mental rotation
      task. However, direct neurophysiologic evidence for the effect of prosthesis use
      on hand mental rotation is still lacking. In this paper, we recruited two groups
      of unilateral upper-limb amputees, i.e., amputees using a prosthesis or with a
      history of prosthesis use (Pro group) and amputees without a prosthesis (non-Pro
      group), as well as a sample of matched healthy controls. Using concurrent
      behavioral and electrophysiological assessments, we found that Pro amputees were
      comparable to healthy controls in either behavior or event-related potentials
      (ERPs), while non-Pro amputees showed prolonged response time as well as
      divergent ERP patterns. The P200 amplitude of non-Pro amputees was significantly
      larger for the non-dominant hand pictures than that for the dominant hand
      pictures, while such a hand difference in P200 was not found in either healthy
      controls or Pro amputees. Furthermore, the typical angular modulation of the N200
      amplitude in healthy controls and Pro amputees was not presented in non-Pro
      amputees. Our results suggest that prosthesis use could preserve mental rotation
      ability by maintaining the performance of motor imagery and visual perception of
      hands, which represents a preservation of the body schema.

PMID- 28489544
TI  - An Improved Approach for N-linked Glycan Structure Identification from HCD MS/MS
      Spectra.
AB  - Glycosylation is a frequently observed posttranslational modification on
      proteins. Currently, tandem mass spectrometry (MS/MS) serves as an efficient
      analytical technique for characterizing structures of oligosaccharides. However,
      developing effective computational approaches for identifying glycan structures
      from mass spectra is still a great challenge in glycoproteomics research. In this
      study, we proposed an approach for matching the input spectra with glycan
      structures acquired from a glycan structure database by incorporating a de novo
      sequencing assisted ranking scheme. The proposed approach is implemented as a
      software tool, GlycoNovoDB, for automated glycan structure identification from
      HCD MS/MS of glycopeptides. Experimental results showed that GlycoNovoDB can
      identify glycans effectively and has better performance than our previously
      proposed de novo sequencing algorithm as well as another software GlycoMaster DB.

PMID- 28489545
TI  - Learning a structural and functional representation for gene expressions: To
      systematically dissect complex cancer phenotypes.
AB  - Cancer is a heterogeneous disease, thus one of the central problems is how to
      dissect the resulting complex phenotypes in terms of their biological building
      blocks. Computationally, this is to represent and interpret high dimensional
      observations through a structural and conceptual abstraction into the most
      influential determinants underlying the problem. The working hypothesis of this
      report is to consider gene interaction to be largely responsible for the
      manifestation of complex cancer phenotypes, thus where the representation is to
      be conceptualized. Here we report a representation learning strategy combined
      with regularizations, in which gene expressions are described in terms of a
      regularized product of meta-genes and their expression levels. The meta-genes are
      constrained by gene interactions thus representing their original topological
      contexts. The expression levels are supervised by their conditional dependencies
      among the observations thus providing a cluster-specific constraint. We obtain
      both of these structural constraints using a node-based graphical model. Our
      representation allows the selection of more influential modules, thus implicating
      their possible roles in neoplastic transformations. We validate our
      representation strategy by its robust recognitions of various cancer phenotypes
      comparing with various classical methods. The modules discovered are either
      shared or specify for different types or stages of human cancers, all of which
      are consistent with literature and biology.

PMID- 28489546
TI  - A Novel AMARS Technique for Baseline Wander Removal Applied to
      Photoplethysmogram.
AB  - A new digital filter, AMARS (aligning minima of alternating random signal) has
      been derived using trigonometry to regulate signal pulsations inline. The pulses
      are randomly presented in continuous signals comprising frequency band lower than
      the signal's mean rate. Frequency selective filters are conventionally employed
      to reject frequencies undesired by specific applications. However, these
      conventional filters only reduce the effects of the rejected range producing a
      signal superimposed by some baseline wander (BW). In this work, filters of
      different ranges and techniques were independently configured to preprocess a
      photoplethysmogram, an optical biosignal of blood volume dynamics, producing wave
      shapes with several BWs. The AMARS application effectively removed the
      encountered BWs to assemble similarly aligned trends. The removal implementation
      was found repeatable in both ear and finger photoplethysmograms, emphasizing the
      importance of BW removal in biosignal processing in retaining its structural,
      functional and physiological properties. We also believe that AMARS may be
      relevant to other biological and continuous signals modulated by similar types of
      baseline volatility.

PMID- 28489547
TI  - A 172 $?mu$W Compressively Sampled Photoplethysmographic (PPG) Readout ASIC With
      Heart Rate Estimation Directly From Compressively Sampled Data.
AB  - A compressive sampling (CS) photoplethysmographic (PPG) readout with embedded
      feature extraction to estimate heart rate (HR) directly from compressively
      sampled data is presented. It integrates a low-power analog front end together
      with a digital back end to perform feature extraction to estimate the average HR
      over a 4 s interval directly from compressively sampled PPG data. The application
      specified integrated circuit (ASIC) supports uniform sampling mode (1x
      compression) as well as CS modes with compression ratios of 8x, 10x, and 30x. CS
      is performed through nonuniformly subsampling the PPG signal, while feature
      extraction is performed using least square spectral fitting through Lomb-Scargle
      periodogram. The ASIC consumes 172  MU W of power from a 1.2 V supply while
      reducing the relative LED driver power consumption by up to 30 times without
      significant loss of relevant information for accurate HR estimation.

PMID- 28489548
TI  - Retinal Circuit Emulator With Spatiotemporal Spike Outputs at Millisecond
      Resolution in Response to Visual Events.
AB  - To gain insights on how visual information of the real world is filtered,
      compressed, and encoded by the vertebrate retinas, emulating in silico the
      spatiotemporal patterns of the graded and action potentials of neuronal responses
      to natural visual scenes on biological time scale is a feasible approach. As a
      basic platform for such an emulation, we here developed a compact hardware system
      comprising an analog silicon retina and a field-programmable gate array module.
      With utilizing the Izhikevich formalism, a retinal circuit model that emulates
      spiking of ganglion cells was implemented in this system. The emulated spike
      timing had the resolution of about 2 ms relative to the stimulus onset and was
      little affected by timings of the synchronous frame sampling in the silicon
      retina. Thus, the emulator can mimic the event-driven spike outputs of biological
      retinas. The system was useful for simultaneously visualizing neural images of
      both the graded potentials and the spikes in response to real live visual scenes.
      Since our emulator system is reconfigurable, it provides a flexible platform for
      investigating visual functions of retinal circuits under natural visual
      environment.

PMID- 28489549
TI  - Secure and Energy-Efficient Data Transmission System Based on Chaotic Compressive
      Sensing in Body-to-Body Networks.
AB  - Applications of wireless body area networks (WBANs) are extended from remote
      health care to military, sports, disaster relief, etc. With the network scale
      expanding, nodes increasing, and links complicated, a WBAN evolves to a body-to
      body network. Along with the development, energy saving and data security
      problems are highlighted. In this paper, chaotic compressive sensing (CCS) is
      proposed to solve these two crucial problems, simultaneously. Compared with the
      traditional compressive sensing, CCS can save vast storage space by only storing
      the matrix generation parameters. Additionally, the sensitivity of chaos can
      improve the security of data transmission. Aimed at image transmission, modified
      CCS is proposed, which uses two encryption mechanisms, confusion and mask, and
      performs a much better encryption quality. Simulation is conducted to verify the
      feasibility and effectiveness of the proposed methods. The results show that the
      energy efficiency and security are strongly improved, while the storage space is
      saved. And the secret key is extremely sensitive, [Formula: see text]
      perturbation of the secret key could lead to a total different decoding, the
      relative error is larger than 100%. Particularly for image encryption, the
      performance of the modified method is excellent. The adjacent pixel correlation
      is smaller than 0.04 in different directions including horizontal, vertical, and
      diagonal; the entropy of the cipher image with a 256-level gray value is larger
      than 7.98.

PMID- 28489551
TI  - On the Dynamics of Hopfield Neural Networks on Unit Quaternions.
AB  - In this paper, we first address the dynamics of the elegant multivalued
      quaternionic Hopfield neural network (MV-QHNN) proposed by Minemoto et al.
      Contrary to what was expected, we show that the MV-QHNN, as well as one of its
      variation, does not always come to rest at an equilibrium state under the usual
      conditions. In fact, we provide simple examples in which the network yields a
      periodic sequence of quaternionic state vectors. Afterward, we turn our attention
      to the continuous-valued quaternionic Hopfield neural network (CV-QHNN), which
      can be derived from the MV-QHNN by means of a limit process. The CV-QHNN can be
      implemented more easily than the MV-QHNN model. Furthermore, the asynchronous CV
      QHNN always settles down into an equilibrium state under the usual conditions.
      Theoretical issues are all illustrated by examples in this paper.

PMID- 28489550
TI  - A Fully Integrated Wireless SoC for Motor Function Recovery After Spinal Cord
      Injury.
AB  - This paper presents a wirelessly powered, fully integrated system-on-a-chip (SoC)
      supporting 160-channel stimulation, 16-channel recording, and 48-channel bio
      impedance characterization to enable partial motor function recovery through
      epidural spinal cord electrical stimulation. A wireless transceiver is designed
      to support quasi full-duplex data telemetry at a data rate of 2 Mb/s.
      Furthermore, a unique in situ bio-impedance characterization scheme based on time
      domain analysis is implemented to derive the Randles cell electrode model of the
      electrode-electrolyte interface. The SoC supports concurrent stimulation and
      recording while the high-density stimulator array meets an output compliance
      voltage of up to +/-10 V with versatile stimulus programmability. The SoC
      consumes 18 mW and occupies a chip area of 5.7 mm * 4.4 mm using 0.18 MUm high
      voltage CMOS process. In our in vivo rodent experiment, the SoC is used to
      perform wireless recording of EMG responses while stimulation is applied to
      enable the standing and stepping of a paralyzed rat. To facilitate the system
      integration, a novel thin film polymer packaging technique is developed to
      provide a heterogeneous integration of the SoC, coils, discrete components, and
      high-density flexible electrode array, resulting in a miniaturized prototype
      implant with a weight and form factor of 0.7 g and 0.5 cm3, respectively.

PMID- 28489552
TI  - Structure Learning for Deep Neural Networks Based on Multiobjective Optimization.
AB  - This paper focuses on the connecting structure of deep neural networks and
      proposes a layerwise structure learning method based on multiobjective
      optimization. A model with better generalization can be obtained by reducing the
      connecting parameters in deep networks. The aim is to find the optimal structure
      with high representation ability and better generalization for each layer. Then,
      the visible data are modeled with respect to structure based on the products of
      experts. In order to mitigate the difficulty of estimating the denominator in
      PoE, the denominator is simplified and taken as another objective, i.e., the
      connecting sparsity. Moreover, for the consideration of the contradictory nature
      between the representation ability and the network connecting sparsity, the
      multiobjective model is established. An improved multiobjective evolutionary
      algorithm is used to solve this model. Two tricks are designed to decrease the
      computational cost according to the properties of input data. The experiments on
      single-layer level, hierarchical level, and application level demonstrate the
      effectiveness of the proposed algorithm, and the learned structures can improve
      the performance of deep neural networks.

PMID- 28489553
TI  - Data-Driven Learning Control for Stochastic Nonlinear Systems: Multiple
      Communication Constraints and Limited Storage.
AB  - This paper proposes a data-driven learning control method for stochastic
      nonlinear systems under random communication conditions, including data dropouts,
      communication delays, and packet transmission disordering. A renewal mechanism is
      added to the buffer to regulate the arrived packets, and a recognition mechanism
      is introduced to the controller for the selection of suitable update packets.
      Both intermittent and successive update schemes are proposed based on the
      conventional P-type iterative learning control algorithm, and are shown to
      converge to the desired input with probability one. The convergence and
      effectiveness of the proposed algorithms are verified by means of illustrative
      simulations.

PMID- 28489554
TI  - Reversed Spectral Hashing.
AB  - Hashing is emerging as a powerful tool for building highly efficient indices in
      large-scale search systems. In this paper, we study spectral hashing (SH), which
      is a classical method of unsupervised hashing. In general, SH solves for the hash
      codes by minimizing an objective function that tries to preserve the similarity
      structure of the data given. Although computationally simple, very often SH
      performs unsatisfactorily and lags distinctly behind the state-of-the-art
      methods. We observe that the inferior performance of SH is mainly due to its
      imperfect formulation; that is, the optimization of the minimization problem in
      SH actually cannot ensure that the similarity structure of the high-dimensional
      data is really preserved in the low-dimensional hash code space. In this paper,
      we, therefore, introduce reversed SH (ReSH), which is SH with its input and
      output interchanged. Unlike SH, which estimates the similarity structure from the
      given high-dimensional data, our ReSH defines the similarities between data
      points according to the unknown low-dimensional hash codes. Equipped with such a
      reversal mechanism, ReSH can seamlessly overcome the drawback of SH. More
      precisely, the minimization problem in our ReSH can be optimized if and only if
      similar data points are mapped to adjacent hash codes, and mostly important,
      dissimilar data points are considerably separated from each other in the code
      space. Finally, we solve the minimization problem in ReSH by multilayer neural
      networks and obtain state-of-the-art retrieval results on three benchmark data
      sets.

PMID- 28489555
TI  - Distributed Adaptive Containment Control for a Class of Nonlinear Multiagent
      Systems With Input Quantization.
AB  - This paper is devoted to distributed adaptive containment control for a class of
      nonlinear multiagent systems with input quantization. By employing a matrix
      factorization and a novel matrix normalization technique, some assumptions
      involving control gain matrices in existing results are relaxed. By fusing the
      techniques of sliding mode control and backstepping control, a two-step design
      method is proposed to construct controllers and, with the aid of neural networks,
      all system nonlinearities are allowed to be unknown. Moreover, a linear time
      varying model and a similarity transformation are introduced to circumvent the
      obstacle brought by quantization, and the controllers need no information about
      the quantizer parameters. The proposed scheme is able to ensure the boundedness
      of all closed-loop signals and steer the containment errors into an arbitrarily
      small residual set. The simulation results illustrate the effectiveness of the
      scheme.

PMID- 28489556
TI  - Modeling the Length of Stay of Respiratory Patients in Emergency Department Using
      Coxian Phase-Type Distributions With Covariates.
AB  - Variability and unpredictability are typical features of emergency departments
      (EDs) where patients randomly arrive with diverse conditions. Patient length of
      stay (LOS) represents the consumption level of hospital resources, and it is
      positively skewed and heterogeneous. Both accurate modeling of patient ED LOS and
      analysis of potential blocking causes are especially useful for patient
      scheduling and resource management. To tackle the uncertainty of ED LOS, this
      paper introduces two methods: statistical modeling and distribution fitting. The
      models are applied to 894 respiratory diseases patients data in the year 2014
      from ED of a Chinese public tertiary hospital. Covariates recorded include
      patient region, gender, age, arrival time, arrival mode, triage category, and
      treatment area. A Coxian phase-type (PH) distribution model with covariates is
      proposed as an alternative method for modeling ED LOS. The expectation
      maximization (EM) algorithm is used to implement parameter estimation. The
      results show that ED LOS data can be modeled well by the proposed models.
      Distributions of ED LOS differ significantly with respect to patients' gender,
      arrival mode, and treatment area. Using the fitted Coxian PH model will assist ED
      managers in identifying patients who are most likely to have an extreme ED LOS
      and in predicting the forthcoming workload for resources.

PMID- 28489557
TI  - Reduced bone mineral density in Chinese children with phenylketonuria.
AB  - BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder.
      Dietary control of classic PKU needs restriction of natural proteins. The diet
      results in unbalanced nutrition, which might affect the physical development of
      the patients. Our aim was to evaluate bone mineral density (BMD) in children with
      PKU. METHODS: To investigate the BMD of children with PKU, 41 children with PKU
      and 64 healthy controls were recruited (all 3-4 years of age). Body weight and
      height, BMD, Phe blood levels, thyroid function, calcium, phosphorus, iron
      metabolism markers, and vitamin D3 were measured. RESULTS: Body height and BMD of
      patients were lower than in controls. The BMD of controls was positively
      associated with age, body weight and height. In patients, BMD was positively
      associated with body weight. There was no correlation between Phe blood levels
      and BMD in patients. Blood levels of alkaline phosphatase were higher in patients
      compared to controls. Blood calcium levels were higher in 4-year-old patients,
      while the body weight was lower compared to controls. Thyroid function, iron
      metabolism markers, vitamin D3 levels and IGF-1 levels were normal. CONCLUSIONS:
      Reduced BMD was observed in children with phenylketonuria, but the exact reasons
      for this remain to be elucidated.

PMID- 28489558
TI  - Evaluation of factors associated with elevated newborn 17-hydroxyprogesterone
      levels.
AB  - BACKGROUND: Measurement of 17-hydroxyprogesterone (17-OHP) in dried blood spots
      has been widely used as a newborn screening tool for congenital adrenal
      hyperplasia (CAH). Various maternal and neonatal factors can result in falsely
      high values of 17-OHP. There is a paucity of Indian studies in this regard
      because routine evaluation of newborn 17-OHP levels as a screening program is not
      widely practiced in India. Hence, this study was undertaken to evaluate the
      influence of various maternal and neonatal factors on newborn 17-OHP levels. The
      aim of the study was to determine the effect of various maternal and neonatal
      factors on the newborn 17-OHP values. METHODS: Retrospective data related to a
      total of 3080 newborn 17-OHP values and clinical characteristics were collected
      for 3 years (2013-2015). The data were analyzed to determine the influence of
      various factors on 17-OHP values. RESULTS: The mean value of 17-OHP in our study
      was 5.486+/-3.96 ng/mL. Gender and mode of delivery did not significantly affect
      the 17-OHP levels. The levels were significantly higher in preterm and low birth
      weight babies as compared to term babies and babies with normal birth weight.
      Stress factors like pregnancy induced hypertension (PIH), early onset sepsis
      (EOS), neonatal seizures and birth asphyxia significantly increase the neonatal
      17-OHP levels. CONCLUSIONS: The levels of 17-OHP in newborns was measured around
      day 3 of life are very sensitive to the influence of gestational age, birth
      weight and presence of stress factors like maternal PIH, birth asphyxia, neonatal
      sepsis and neonatal seizures and should be interpreted cautiously.

PMID- 28489560
TI  - Peripartum cardiomyopathy - from pathogenesis to treatment.

PMID- 28489559
TI  - Neck circumference is similarly predicting for impairment of glucose tolerance as
      classic anthropometric parameters among healthy and obese children and
      adolescents.
AB  - BACKGROUND: The objective of the study was to investigate the association of neck
      circumference (NC) to parameters of glucose homeostasis compared to classical
      anthropometric parameters of lean and obese children. METHODS: Three dimensional
      (3D)-body scanning quantified anthropometric (height, weight, NC, hip/waist
      circumference, BMI) and metabolic parameters (fasting plasma glucose [FPG],
      insulin, HbA1c, oGTT, HOMA-IR) were determined cross-sectionally in 1542
      participants (5-18 years). RESULTS: NC was positively correlated with all
      metabolic parameters, except for FPG. For HbA1c there was only a modestly
      positive correlation. The associations between NC and glucose parameters were
      rather weak, while the correlation to insulin parameters were stronger. Overall
      the strongest association to glucose metabolism parameters was found for waist
      circumference (WC), except for FPG and 2h-postload glucose. In multiple linear
      regression analyses, NC provided additional benefit beyond classical
      anthropometric indices to describe impairment of glucose homeostasis.
      CONCLUSIONS: We suggest that NC is comparable or additive to established
      anthropometric parameters but might not be superior to them. However NC is simple
      to measure, reproducible and may be considered in clinical practice as an
      additional measurement tool.

PMID- 28489561
TI  - 3D power Doppler in the evaluation of abnormally invasive placenta.
AB  - The anomalies in placental insertion and invasion, such as placenta previa and
      the various forms of abnormally invasive placenta, are today a rising obstetric
      pathology. Two-dimensional (2D) ultrasonography is the gold standard in the
      diagnosis of abnormally invasive placenta (AIP), but the important feto-maternal
      impact of this pathology suggests the opportunity to employ all the available
      diagnostic techniques, such as three-dimensional (3D) power Doppler. This
      technique allows acquiring multiplanar images on coronal, axial and sagittal
      planes and with a rotational technique, it permits visualizing the placenta
      bladder interface more accurately. Consequently, it allows a better study of the
      degree of bladder invasion, which is information that has a great impact on the
      subsequent counseling and management. Thus, 3D power Doppler represents an
      important technique complementary to 2D ultrasound in the diagnosis of AIP. The
      aim of this paper is to illustrate the possible applications of this procedure,
      referring to the main literature data.

PMID- 28489562
TI  - Incidence of menopausal symptoms in postmenopausal breast cancer patients treated
      with aromatase inhibitors.
AB  - Aromatase inhibitors (AIs) are the standard of care for postmenopausal women with
      estrogen receptor-positive breast cancer. Here, we performed a meta-analysis to
      evaluate the occurrence of menopausal symptoms in breast cancer patients
      receiving the AI therapy. Patients treated with AIs had an increased risk of all
      grade arthralgia (1.63 [95% CI: 1.34-1.98]) and insomnia (1.24 [95% CI: 1.14
      1.34]). The overall incidence of hot flashes, fatigue, arthralgia, sweating, and
      insomnia in patients receiving AIs was 30.47% (95% CI: 25.51%-35.93%), 17.16%
      (95% CI: 14%-20.85%), 17.91% (95% CI: 11.29%-27.22%), 14.64% (95% CI: 11.46%
      18.52%), and 16.52% (95% CI: 12.45%-21.6 %), respectively. Both arthralgia (RR =
      0.34, 95% CI: 0.16-0.75) and sweating (RR = 11.02, 95% CI: 4.11-29.57) differed
      between patients with early- and advanced-stage breast cancer. Our findings
      indicates that AIs are associated with a significant risk of developing
      arthralgia and insomnia in breast cancer patients. Effective early detection and
      management of menopausal symptoms would likely lead to safer use of AIs in breast
      cancer patients.

PMID- 28489563
TI  - Efficacy of fibrin glue versus sutures for attaching conjunctival autografts in
      pterygium surgery: a systematic review with meta-analysis and trial sequential
      analysis of evidence.
AB  - Previous meta-analyses have been conducted to compare the efficacy of fibrin glue
      (FG) versus sutures in pterygium surgery; however, additional clinical trials
      have since been published. Therefore, we conducted an updated meta-analysis to
      further explore the association between FG application in pterygium surgery, and
      the recurrence rate, complication rate, and surgical duration. An electronic
      literature search for eligible studies published before July 29, 2016 was
      conducted across multiple databases. Odds ratios (ORs), standardized mean
      difference (SMD), and 95% confidence intervals (CI) were calculated. Publication
      bias of the included articles was evaluated by funnel plots. Differences in
      recurrence rate and complication rate between the FG and suture groups were
      evaluated in terms of OR with 95% CI, and SMD with 95% CI were used to estimate
      the difference in surgical duration. Trial sequential analysis (TSA) was used to
      determine whether the currently available evidence was sufficient and conclusive.
      Twenty-four studies were included in this study. The pooled ORs for recurrence
      rate and complication rate were 0.35 and 1.121, respectively. The pooled SMD for
      surgical duration was -4.142. The TSA results indicated that evidence of the
      effect was sufficient in the recurrence group and surgical duration group.
      Although there was no difference in complication rate between FG and sutures, the
      apparent advantages of FG over sutures are shorter surgical duration and greater
      reduction in the recurrence rate of pterygium.

PMID- 28489564
TI  - YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular
      carcinoma cells to HDAC inhibitor.
AB  - YY1 is a DNA-binding transcription factor and reported to be involved in cancer
      progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation
      and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is
      unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this
      study, firstly, we identified two drug-response profiles to HDACi in HCC cell
      lines, while our results showed that HDAC1 expression was positively correlated
      with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the
      sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found
      that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in
      turn up-regulated the expression of YY1. In conclusion, our results showed that
      YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential
      therapeutic target in HCC.

PMID- 28489565
TI  - Motifs in the amino-terminus of CENP-A are required for its accumulation within
      the nucleus and at the centromere.
AB  - Centromere protein A (CENP-A) is a variant of core histone H3 that marks the
      centromere's location on the chromosome. The mechanisms that target the protein
      to the nucleus and the centromere have not been defined. In this study, we found
      that deletion of the first 53 but not the first 29 residues of CENP-A from the
      amino-terminus, resulted in its cytoplasmic localization. Two motifs, R42R43R44
      and K49R52K53K56, which are reported to be required for DNA contact in the
      centromere nucleosome, were found to be critical for CENP-A nuclear accumulation.
      These two motifs potentially mediated its interaction with Importin-beta but were
      not involved in CENP-A centromeric localization. A third novel motif,
      L60L61I62R63K64, was found to be essential for the centromeric accumulation of
      CENP-A. The nonpolar hydrophobic residues L60L61I62, but not the basic residues
      R63K64, were found to be the most important residues. A protein interaction assay
      suggested that this motif is not involved in the interaction of CENP-A with its
      deposition factors but potentially mediates its interaction with core histone H4
      and CENP-B. Our study uncovered the role of the amino-terminus of CENP-A in
      localization.

PMID- 28489567
TI  - Eg5 inhibitor YL001 induces mitotic arrest and inhibits tumor proliferation.
AB  - Eg5 is a kinesin spindle protein that controls chromosomal segregation in mitosis
      and is thus a critical drug target for cancer therapy. We report the discovery of
      a potent, selective inhibitor of Eg5 designated YL001. YL001 was obtained through
      shape similarity based virtual screening, and it bears a 1,5-disubstituted
      tetrazole scaffold. YL001 exhibits favorable bioactivity in a variety of cancer
      cell lines, including taxol-resistant ovarian cancer and 6TG-resistant breast
      cancer cell lines. This compound inhibits tumor growth by 60% and significantly
      prolongs median survival time by more than 50% in a xenograft mouse model. YL001
      blocks the ATPase activity of Eg5 and causes mitotic failure, ultimately
      resulting in apoptosis of cancer cells through activation of the caspase-3
      pathway. Our findings demonstrate that YL001 is a potent antitumor agent that may
      be developed for cancer therapeutics.

PMID- 28489568
TI  - Efficacy and safety of decitabine in treatment of elderly patients with acute
      myeloid leukemia: A systematic review and meta-analysis.
AB  - Elderly patients with acute myeloid leukemia (AML) have limited treatment options
      concerned about their overall fitness and potential treatment related mortality.
      Although a number of clinical trials demonstrated benefits of decitabine
      treatment in elderly AML patients, the results remains controversial. A meta
      analysis was performed to evaluate efficacy and safety of decitabine in treatment
      of elderly AML patients. Eligible studies were identified from PubMed, Web of
      Science, Embase and Cochrane Library. Nine published studies were included in the
      meta-analysis, enrolling 718 elderly AML patients. The efficacy outcomes were
      complete remission (CR), overall response rate (ORR) and overall survival (OS).
      Safety was evaluated based on treatment related grades 3-4 adverse events (AEs)
      and early death (ED) rate. Pooled estimates with 95% confidence interval (CI) for
      CR, ORR and OS were 27% (95% CI 19%-36%), 37% (95% CI 28%-47%) and 8.09 months
      (95% CI 5.77-10.41), respectively. The estimated treatment related early death
      (ED) incidences were within 30-days 7% (95% CI 2%-11%) and 60-days 17% (95% CI
      11%-22%), respectively. Thrombocytopenia was the most common grades 3-4 AEs.
      Subgroup analyses of age, cytogenetics risk, AML type and bone marrow blast
      percentage showed no significant differences of treatment response to decitabine.
      In conclusion, decitabine is an effective and well-tolerated therapeutic
      alternative with acceptable side effects in elderly AML patients.

PMID- 28489569
TI  - Statin use and survival outcomes in endocrine-related gynecologic cancers: A
      systematic review and meta-analysis.
AB  - Previous studies investigating the association between statin use and survival
      outcomes in gynecologic cancers have yielded controversial results. We conducted
      a systematic review and meta-analysis to evaluate the association based on
      available evidence. We searched the databases of the Cochrane Central Register of
      Controlled Trials (CENTRAL), Embase, and PubMed from inception to January 2017.
      Studies that evaluated the association between statin use and survival outcomes
      in gynecologic cancers were included. Pooled hazard ratios (HRs) for overall
      survival, disease-specific survival and progression-free survival were calculated
      using a fixed-effects model. A total of 11 studies involving more than 6,920
      patients with endocrine-related gynecologic cancers were identified. In a meta
      analysis of 7 studies involving 5,449 patients with endocrine-related gynecologic
      cancers, statin use was linked to improved overall survival (HR, 0.71; 95%
      confidence interval [CI], 0.63 to 0.80) without significant heterogeneity (I2 =
      33.3%). Statin users also had improved disease-specific survival (3 studies, HR,
      0.72; 95% CI, 0.58 to 0.90, I2 = 35.1%) and progression-free survival (3 studies,
      HR, 0.68; 95% CI, 0.49 to 0.93, I2 = 33.6%) in endocrine-related gynecologic
      cancers. Our findings support that statin use has potential survival benefits for
      patients with endocrine-related gynecologic cancers. Further large-scale
      prospective studies are required to validate our findings.

PMID- 28489570
TI  - Transcriptome profiling identifies a recurrent CRYL1-IFT88 chimeric transcript in
      hepatocellular carcinoma.
AB  - We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and
      adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC
      patients were recruited and differentially expressed genes (DEGs) were
      identified. Candidate fusion transcripts were also identified. A total of 1943
      DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and
      enriched in ten pathways including cell cycle, DNA replication, p53, complement
      and coagulation cascades, etc. Seven candidate fusion genes were detected and
      CRYL1-IFT88 was successfully validated in the discovery sequencing sample and
      another 5 tumor samples with the recurrent rate of about 9.52% (6/63). The full
      length of CRYL1-IFT88 was obtained by 3' and 5' RACE. The function of the fusion
      transcript is closed to CRYL1 because it contained most of domain of CRYL1.
      According to the bioinformatics analysis, IFT88, reported as a tumor suppressor,
      might be seriously depressed in the tumor cell with this fusion because the
      transcript structure of IFT88 was totally changed. The function depression of
      IFT88 caused by gene fusion CRYL1-IFT88 might be associated with tumorigenesis or
      development of HCC.

PMID- 28489571
TI  - Analysis of STAT3 post-translational modifications (PTMs) in human prostate
      cancer with different Gleason Score.
AB  - Prostate Cancer (PCa) is a complex and heterogeneous disease. The androgen
      receptor (AR) and the signal transducer and activator of transcription 3 (STAT3)
      could be effective targets for PCa therapy. STAT3, a cytoplasmatic latent
      transcription factor, is a hub protein for several oncogenic signalling pathways
      and up-regulates the expression of numerous genes involved in tumor cell
      proliferation, angiogenesis, metastasis and cell survival. STAT3 activity can be
      modulated by several Post-Translational Modifications (PTMs) which reflect
      particular cell conditions and may be implicated in PCa development and
      progression. The aim of this work was to analyze STAT3 PTMs at different tumor
      stages and their relationship with STAT3 cellular functions. For this purpose,
      sixty-five prostatectomy, Formalin-fixed paraffin-embedded (FFPE) specimens,
      classified with different Gleason Scores, were subjected to immunoblotting,
      immunofluorescence staining and RT-PCR analysis. All experiments were carried out
      in matched non-neoplastic and neoplastic tissues. Data obtained showed different
      STAT3 PTMs profiles among the analyzed tumor grades which correlate with
      differences in the amount and distribution of specific STAT3 interactors as well
      as the expression of STAT3 target genes. These results highlight the importance
      of PTMs as an additional biomarker for the exactly evaluation of the PCa stage
      and the optimal treatment of this disease.

PMID- 28489573
TI  - Recombinant SjP40 protein enhances p27 promoter expression in hepatic stellate
      cells via an E2F1-dependent mechanism.
AB  - The p27 protein plays a critical role in cell cycle arrest. Our previous studies
      have demonstrated that recombinant P40 protein from Schistosoma japonicum
      (rSjP40) could induce G1 phase arrest of cell cycle. We, therefore, attempted to
      observe the effect of rSjP40 on p27 promoter activity in LX-2 cells and to
      explore its potential mechanisms in this study. Using both Western blot and dual
      luciferase reporter assay, we demonstrated that rSjP40 could enhance the
      expression of p27 in LX-2 cells. Results obtained using truncated fragments of
      p27 promoter showed that rSjP40 increased p27 promoter activity in LX-2 cells,
      mainly via some transcription factors that bind to the -1740/-873 region of p27
      promoter. Further studies confirmed that the enhancement of p27 promoter activity
      induced by rSjP40 was related to E2F1 in LX-2 cells. Transfection of siRNA of
      E2F1 could also restore the effect of rSjP40 on expression of p27 and partially
      on alpha-SMA. Therefore, our study provided further insights into the mechanism
      by which rSjP40 induces LX-2 cell cycle arrest at G1 phase and inhibits HSC
      activation. Our results provide basis for future study of the blocking effect of
      rSjP40 in liver fibrosis.

PMID- 28489572
TI  - CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic
      leukaemia.
AB  - Despite the encouraging results of the innovative therapeutic treatments,
      complete remission is uncommon in patients affected by chronic lymphocytic
      leukaemia, which remains an essentially incurable disease. Recently, clinical
      trials based on BH3-mimetic drugs showed positive outcomes in subjects with poor
      prognostic features. However, resistance to treatments occurs in a significant
      number of patients. We previously reported that the multi-kinase inhibitor
      quercetin, a natural flavonol, restores sensitivity to ABT-737, a BH3-mimetic
      compound, in both leukemic cell lines and B-cells isolated from patients. To
      identify the molecular target of quercetin, we employed a new cell line, HG3,
      obtained by immortalization of B-cells from a chronic lymphocytic leukaemia
      patient at the later stage of disease. We confirmed that quercetin in association
      with ABT-737 synergistically enhances apoptosis in HG3 (combination index < 1 for
      all fractions affected). We also reported that the cellular uptake of quercetin
      is extremely rapid, with an intracellular concentration of about 38.5 ng/106
      cells, after treatment with 25 MUM for 5 min. We demonstrated that the activity
      of protein kinase CK2, which positively triggers PI3K/Akt pathway by inactivating
      PTEN phosphatase, is inhibited by quercetin immediately after its addition to HG3
      cells (0-2 min). PI3K activity was also inhibited by quercetin within 60 min from
      the treatment. The combined inhibition of CK2 and PI3K kinase activities by
      quercetin restored ABT-737 sensitivity and increased lethality in human leukemia
      cells.

PMID- 28489574
TI  - Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer
      treatment.
AB  - Angiogenesis is essential for tumor growth and metastasis, controlling
      angiogenesis is a promising strategy in cancer treatment. However, thus farther
      severe side effects of anti-angiogenic drugs have been rather demonstrated,
      stimulating interest in seeking novel targets of anti-angiogenesis. Neurokinin
      receptors, also known as tachykinin receptors, are usually considered as drug
      targets due to diverse physiological functions and their tractability. Although
      Neurokinin B, the selective natural agonist of neurokinin-3 receptor, have been
      shown to exhibit anti-angiogenesis activity, the effect and mechanism of
      neurokinin-3 receptor-mediated angiogenesis still remains unclear. In the present
      study, we demonstrated that [Mephe7]NKB, an analogue of NKB, possess significant
      anti-angiogenic effect on CAM. Furthermore, by introducing the tumor angiogenesis
      homing sequence (NGR), we designed and synthesized two novel agonist analogues of
      NK3R, NK3R-A1 and NK3R-A2. Both of the two analogues exhibit more efficient anti
      migration effect on HUVECs by activating NK3R in vitro, and showed potent
      antitumor activities with no significant side effects in vivo. Taken together,
      our results illuminated that NK3R might be a potential novel target for the anti
      angiogenesis therapy. Notably, NK3R-A1 might be used as a template for the
      development of the anti-tumor drugs on the basis of the anti-angiogenesis
      strategy.

PMID- 28489575
TI  - Evaluation of 99mTc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR
      activating mutations in NSCLC.
AB  - Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor
      receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years
      with promising results, in particular in patients with activating mutations in
      the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point
      mutation). However, despite their great success in the clinic, a significant
      number of patients do not respond to EGFR-TKIs, such as those carrying the
      L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status
      before EGFR-TKIs therapy is essential to ensure its efficacy. In this study, we
      report a novel SPECT tracer 99mTc-HYNIC-MPG that binds specifically to activating
      mutant EGFR and which could therefore be used to noninvasively select patients
      sensitive to EGFR-TKIs. We evaluated the capacity of 99mTc-HYNIC-MPG in detecting
      EGFR-activating mutations both in vitro and in vivo using four human NSCLC cell
      lines (PC9, H1975, H358 and H520). 99mTc-HYNIC-MPG had significantly higher
      accumulation in PC9 tumor cells when compared to H1975, H358 and H520 tumors
      cells, which may be due to the activating mutations (exon 19 deletion) in EGFR
      tyrosine kinase domain in PC9 cells. Thus, 99mTc-HYNIC-MPG SPECT imaging may be
      used to identify NSCLC tumors with a potential high response rate to EGFR-TKIs.

PMID- 28489576
TI  - Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation
      in rhesus monkey with spinal cord injury.
AB  - This study tried to quantify spinal cord perfusion by using contrast-enhanced
      ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute
      spinal cord perfusion after injury was detected by CEUS, coupling with
      conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves
      and perfusion parameters were obtained by autotracking contrast quantification
      (ACQ) software in the epicenter and adjacent regions of injury, respectively.
      Neurological and histological examinations were performed to confirm the severity
      of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura
      maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord
      contusion, the injured spinal cord was hyperechoic on US, and intramedullary
      vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS
      hypoperfusion were found in the epicenter of injury, while hyperperfusion in its
      adjacent region. Quantitative analysis showed that peak intensity (PI) decreased
      in epicenters of injury but significantly increased in adjacent regions at all
      time points (p < 0.05). Functional evaluation demonstrated significant
      deterioration compared to pre-contusion (p < 0.05). Quantitative analysis with
      CEUS is a promising method for monitoring perfusion changes of spinal cord injury
      in overall views and real-time.

PMID- 28489577
TI  - Pancreatic cancer ascites xenograft-an expeditious model mirroring advanced
      therapeutic resistant disease.
AB  - Pancreatic ductal adenocarcinoma has limited treatment options. There is an
      urgent need for developing appropriate pre-clinical models recapitulating
      metastatic disease, the most common clinical scenario at presentation. Ascites
      accumulation occurs in up to 20-30% of patients with pancreatic cancer; this
      milieu represents a highly cellular research resource of metastatic peritoneal
      spread. In this study, we utilized pancreatic ascites/pleural effusion cancer
      cells to establish patient derived xenografts.Ascites/pleural effusion-patient
      derived xenografts were established from twelve independent cases. Xenografts
      were serially passed in nude mice and tissue bio-specimen banking has been
      established. Histopathology of emergent tumors demonstrates poorly to moderately
      differentiated, glandular and mucin producing tumors, mirroring morphology of
      primary pancreatic cancer tumors. Whole genome sequencing of six patient derived
      xenografts samples demonstrates common mutations and structural variations
      similar to those reported in primary pancreatic cancer. Xenograft tumors were
      dissociated to single-cells and in-vitro drug sensitivity screen assays
      demonstrated chemo-resistance, correlating with patient clinical scenarios, thus
      serving as a platform for clinically relevant translational research.Therefore,
      establishment of this novel ascites/pleural effusion patient derived xenograft
      model, with extensive histopathology and genomic characterization, opens an
      opportunity for the study of advanced aggressive pancreatic cancer.
      Characterization of metastatic disease and mechanisms of resistance to
      therapeutics may lead to the development of novel drug combinations.

PMID- 28489578
TI  - Inhibiting translesion DNA synthesis as an approach to combat drug resistance to
      DNA damaging agents.
AB  - Anti-cancer agents exert therapeutic effects by damaging DNA. Unfortunately, DNA
      polymerases can effectively replicate the formed DNA lesions to cause drug
      resistance and create more aggressive cancers. To understand this process at the
      cellular level, we developed an artificial nucleoside that visualizes the
      replication of damaged DNA to identify cells that acquire drug resistance through
      this mechanism. Visualization is achieved using "click" chemistry to covalently
      attach azide-containing fluorophores to the ethynyl group present on the
      nucleoside analog after its incorporation opposite damaged DNA. Flow cytometry
      and microscopy techniques demonstrate that the extent of nucleotide incorporation
      into genomic DNA is enhanced by treatment with DNA damaging agents. In addition,
      this nucleoside analog inhibits translesion DNA synthesis and synergizes the
      therapeutic activity of certain anti-cancer agents such as temozolomide. The
      combined diagnostic and therapeutic activities of this synthetic nucleoside
      analog represent a new paradigm in personalized medicine.

PMID- 28489580
TI  - Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38
      MAPK-NFkappaB pathways in autophagy- and p62-dependent manners.
AB  - Excessive and prolonged activation of macrophages underlies many inflammatory and
      autoimmune diseases. To regulate activation and maintain homeostasis, macrophages
      have multiple intrinsic mechanisms, one of which is modulation through autophagy.
      Here we demonstrate that autophagy induction by rapamycin suppressed the
      production of IL-1beta and IL-18 in lipopolysaccharide- and adenosine
      triphosphate-activated macrophages at the post-transcriptional level by
      eliminating mitochondrial ROS (mtROS) and pro-IL1beta in a p62/SQSTM1-dependent
      manner. In addition, rapamycin activated Nrf2 through up-regulation of
      p62/SQSTM1, which further contributed to the reduction of mtROS. Reduced IL-1beta
      subsequently diminished the activation of p38 MAPK-NFkappaB pathways, leading to
      transcriptional down-regulation of IL-6, IL-8, MCP-1, and IkappaBalpha in
      rapamycin-treated macrophages. Therefore, our results suggest that rapamycin
      negatively regulates macrophage activation by restricting a feedback loop of
      NLRP3 inflammasome-p38 MAPK-NFkappaB pathways in autophagy- and p62/SQSTM1
      dependent manners.

PMID- 28489581
TI  - High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR
      pathway: A potential molecular mechanism for diabetes-induced cognitive
      dysfunction.
AB  - The abnormally hyperphosphorylated tau is thought to be implicated in diabetes
      associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) /
      S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been
      previously studied. Caveolin-1 (Cav-1), the essential structure protein of
      caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism.
      In this study, we aimed to investigate the role of Cav-1 in the formation of tau
      hyperphosphorylation under chronic hyperglycemic condition (HGC). Diabetic rats
      were induced by streptozotocin (STZ). Primary hippocampal neurons with or without
      molecular intervention such as the transient over-expression or knock-down were
      subjected to HGC. The obtained experimental samples were analyzed by real time
      quantitative RT-PCR, Western blot, immunofluorescence or immunohistochemisty. We
      found: 1) that a chronic HGC directly decreases Cav-1 expression, increases tau
      phosphorylation and activates mTOR/S6K signalling in the brain neurons of
      diabetic rats, 2) that overexpression of Cav-1 attenuates tau
      hyperphosphorylation induced by chronic HGC in primary hippocampal neurons,
      whereas down-regulation of Cav-1 using Cav-1 siRNA dramatically worsens tau
      hyperphosphorylation via mTOR/S6K signalling pathway, and 3) that the down
      regulation of Cav-1 induced by HGC is independent of mTOR signalling. Our results
      suggest that tau hyperphosphorylation and the sustained over-activated mTOR
      signalling under hyperglycemia may be due to the suppression of Cav-1. Therefore,
      Cav-1 is a potential therapeutic target for diabetes-induced cognitive
      dysfunction.

PMID- 28489583
TI  - Association between vascular endothelial growth factor gene polymorphisms and the
      risk and prognosis of renal cell carcinoma: A systematic review and meta
      analysis.
AB  - The aim of the meta-analysis was to clarify the associations between vascular
      endothelial growth factor (VEGF) polymorphisms and the risk and prognosis of
      renal cell carcinoma (RCC). A meta-analysis was performed by searching the
      databases PubMed, EMBASE and Web of Science for the relevant available studies
      until August 1st, 2016, and fourteen studies met the inclusion criteria. The
      pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to
      evaluate the strength of such associations. Besides, the pooled hazard ratios
      (HRs) with 95% CIs were used to evaluate the overall survival (OS). Fixed- or
      random-effects models were conducted according to existence of heterogeneity.
      Publication bias was evaluated using Begg's funnel plots and Egger's regression
      test. Overall, this meta-analysis included a total of 8,275 patients, who had
      been accrued between November 2002 and September 2015. Meta-analysis indicated
      that -2578C/A, +936C/T and +405G/C polymorphisms in the VEGF gene correlated with
      elevated RCC risk, especially in Asian populations. Moreover, VEGF -1154G/A and 
      634C/G polymorphisms were found significantly associated with poor OS of RCC.
      Therefore, this meta-analysis revealed that VEGF -2578C/A, +936C/T, +405G/C
      polymorphisms were associated with an elevated susceptibility to RCC, indicating
      that these three polymorphisms might be risk factors for RCC, especially in Asian
      populations.

PMID- 28489582
TI  - Association between the ERCC2 Asp312Asn polymorphism and risk of cancer.
AB  - Cancer is the leading cause of death in economically developed countries and the
      second leading cause of death in developing countries. The relationship between
      genetic polymorphisms and the risk of cancers has been widely researched.
      Excision repair cross-complementing group 2 (ERCC2) gene plays important roles in
      the nucleotide excision repair pathway. There is contrasting evidence on the
      association between the ERCC2 Asp312Asn polymorphism and the risk of cancer. We
      conducted a comprehensive meta-analysis in order to assess the correlation
      between these factors. We searched the PubMed, EMBASE, Science Direct, Web of
      Science, and CNKI databases for studies published from January 1, 2005 to January
      1, 2016. Finally, 86 articles with 38,848 cases and 48,928 controls were included
      in the analysis. The overall analysis suggested a significant association between
      the ERCC2 Asp312Asn polymorphism and cancer risk. Furthermore, control source,
      ethnicity, genotyping method, and cancer type were used for subgroup analysis.
      The result of a trial sequential analysis indicated that the cumulative evidence
      is adequate; hence, further trials were unnecessary in the overall analysis for
      homozygote comparison. In summary, our results suggested that ERCC2 Asp312Asn
      polymorphism is associated with increased cancer risk. A significantly increased
      cancer risk was observed in Asian populations, but not in Caucasian populations.
      Furthermore, the ERCC2 Asp312Asn polymorphism is associated with bladder,
      esophageal, and gastric cancers, but not with breast, head and neck, lung,
      prostate, and skin cancers, and non-Hodgkin lymphoma. Further multi-center, well
      designed studies are required to validate our results.

PMID- 28489584
TI  - Transcriptional response profiles of paired tumor-normal samples offer novel
      perspectives in pan-cancer analysis.
AB  - Both tumor and adjacent normal tissues are valuable in cancer research.
      Transcriptional response profiles represent the changes of gene expression levels
      between paired tumor and adjacent normal tissues. In this study, we performed a
      pan-cancer analysis based on the transcriptional response profiles from 633
      samples across 13 cancer types. We obtained two interesting results. Using
      consensus clustering method, we characterized ten clusters with distinct
      transcriptional response patterns and enriched pathways. Notably, head and neck
      squamous cell carcinoma was divided in two subtypes, enriched in cell cycle
      related pathways and cell adhesion-related pathways respectively. The other
      interesting result is that we identified 92 potential pan-cancer genes that were
      consistently upregulated across multiple cancer types. Knockdown of FAM64A or
      TROAP inhibited the growth of cancer cells, suggesting that these genes may
      promote tumor development and are worthy of further validations. Our results
      suggest that transcriptional response profiles of paired tumor-normal tissues can
      provide novel perspectives in pan-cancer analysis.

PMID- 28489585
TI  - POU2F1 over-expression correlates with poor prognoses and promotes cell growth
      and epithelial-to-mesenchymal transition in hepatocellular carcinoma.
AB  - Despite recent efforts to understand activities of POU domain class 2
      transcription factor 1 (POU2F1), little is known about the roles of POU2F1 in
      hepatocellular carcinoma (HCC) tumorigenesis and its correlation with any
      clinicopathological feature of HCC. In this study, we found that POU2F1 was
      significantly up-regulated in HCC specimens compared with adjacent non-cancerous
      liver specimens. The high POU2F1 protein expression level positively correlated
      with large tumor size, high histological grade, tumor metastasis and advanced
      clinical stage, and HCC patients with high POU2F1 levels exhibited poor
      prognoses. We further demonstrated that POU2F1 over-expression promoted HCC cell
      proliferation, colony formation, epithelial-to-mesenchymal transition (EMT),
      migration and invasion, while silencing of POU2F1 inhibited these malignant
      phenotypes. POU2F1 induced the expression of Twist1, Snai1, Snai2 and ZEB1 genes
      which are involved in the regulation of EMT. Furthermore, POU2F1 was up-regulated
      by AKT pathway in HCC, and POU2F1 over-expression reversed the inhibition of
      malignant phenotypes induced by AKT knock-down, indicating POU2F1 is a key down
      stream effector of AKT pathway. Collectively, our results indicate that POU2F1
      over-expression is positively associated with aggressive phenotypes and poor
      survival in patients with HCC, and POU2F1 regulated by AKT pathway promotes HCC
      aggressive phenotypes by regulating the transcription of EMT genes. POU2F1 may be
      employed as a new prognostic factor and therapeutic target for HCC.

PMID- 28489586
TI  - Ephrin-B2/Fc promotes proliferation and migration, and suppresses apoptosis in
      human umbilical vein endothelial cells.
AB  - Tumor growth and metastasis are angiogenesis dependent. Angiogenic growth
      involves endothelial cell proliferation, migration, and invasion. Ephrin-B2 is a
      ligand for Eph receptor tyrosine kinases and is an important mediator in vascular
      endothelial growth factor-mediated angiogenesis. However, research offer
      controversial information regarding effects of ephrin-B2 on vascular endothelial
      cells. In this paper, proteome analyses showed that ephrin-B2/Fc significantly
      activates multiple signaling pathways related to cell proliferation, survival,
      and migration and suppresses apoptosis and cell death. Cytological experiments
      further confirm that ephrin-B2/Fc stimulates endothelial cell proliferation,
      triggers dose-dependent migration, and suppresses cell apoptosis. Results
      demonstrate that soluble dose-dependent ephrinB2 can promote proliferation and
      migration and inhibit apoptosis of human umbilical vein endothelial cells. These
      results also suggest that ephrinB2 prevents ischemic disease and can potentially
      be a new therapeutic target for treating angiogenesis-related diseases and
      tumors.

PMID- 28489587
TI  - NGS based identification of mutational hotspots for targeted therapy in
      anaplastic thyroid carcinoma.
AB  - CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive
      carcinomas with no consistent survival benefit when treated with conventional
      radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are
      increasingly explored and first promising results have been reported in single
      case studies. OBJECTIVE: To determine the prevalence of mutations in known
      thyroid oncogenes and signalling pathways amendable to targeted therapy in a
      large cohort of ATC. RESULTS: In 118 ATC (57 male/ 61 female) a total of 165
      mutations were found. Genes involved in the MAPK/ERK and PI3K pathway (BRAF
      11.0%, HRAS 4.2%, KRAS 7.6%, NRAS 7.6%, PI3KCA 11.8%) were altered in 33%.
      Targetable receptor tyrosine kinases were mutated in 11%. The most frequently
      altered genes were TERT in 86/118 (73%) and p53 in 65/118 (55%) cases. No
      mutations were found analysing ALK, KIT, MET and mTOR. MATERIALS AND METHODS:
      Next generation sequencing (NGS) was performed in FFPE samples from 118 ATC using
      MiSeq (Illumina) and CLC Cancer Research Workbench (CLCbio; Qiagen) for mutation
      analysis in: ALK, BRAF, CDKN2A, EGFR, ERBB2, HRAS, KIT, KRAS, MET, mTOR, NRAS,
      PDGFRA, PI3KCA, p53, RB1, RET and TSC2. Sanger sequencing was used to detect TERT
      promotor mutations. CONCLUSIONS: To our knowledge this is the largest study
      analysing mutations for targeted therapy of ATC. We found that 33% of ATC harbour
      mutations in pathways amendable to targeted therapy. Molecular screening in ATC
      is suggested for targeted therapies since current conventional treatment for ATC
      proved mainly futile.

PMID- 28489589
TI  - Inhibitory effect of ethanol extract of Nannochloropsis oceanica on
      lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogenesis
      and memory impairment.
AB  - Oxidative stress and neuroinflammation is implicated in the pathogenesis and
      development of Alzheimer's disease (AD). Here, we investigated the suppressive
      possibility of ethanol extract of Nannochloropsis oceanica (N. oceanica) on
      memory deficiency along with the fundamental mechanisms in lipopolysaccharide
      (LPS)-treated mice model. Among several extracts of 32 marine microalgae, ethanol
      extract of N. oceanica showed the most significant inhibitory effect on nitric
      oxide (NO) generation, NF-kappaB activity and beta-secretase activity in cultured
      BV-2 cells, neuronal cells and Raw 264.7 cells. Ethanol extract of N. oceanica
      (50, 100 mg/kg) also ameliorated LPS (250 MUg/kg)-induced memory impairment. We
      also found that ethanol extract of N. oceanica inhibited the LPS-induced
      expression of iNOS and COX-2. Furthermore, the production of reactive oxygen
      species (ROS), malondialdehyde (MDA) level as well as glutathione (GSH) level was
      also decreased by treatment of ethanol extract of N.oceanica. The ethanol extract
      of N. oceanica also suppresses IkappaB degradation as well as p50 and p65
      translocation into the nucleus in LPS-treated mice brain. Associated with the
      inhibitory effect on neuroinflammation and oxidative stress, ethanol extract of
      N. oceanica suppressed Abeta1-42 generation through down-regulation of APP and
      BACE1 expression in in vivo. These results suggest that ethanol extract of N.
      oceanica ameliorated memory impairment via anti-inflammatory, anti-oxidant and
      anti-amyloidogenic mechanisms.

PMID- 28489590
TI  - Polymorphisms of VDR gene and risk of gastric cardiac adenocarcinoma in Chinese
      population.
AB  - Vitamin D receptor (VDR) gene polymorphisms have been reported to increase
      susceptibility to some malignant tumors, yet the effect on gastric cardiac
      adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital
      based case-control study to examine the correlation of single nucleotide
      polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A
      and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608
      controls were enrolled in the study. Using ligation detection reaction, we found
      that the variant alleles of the four polymorphisms were not associated with risk
      of gastric cardiac adenocarcinoma. Further stratified analyses showed that there
      was an increased risk associated with VDR rs1989969 polymorphism among patients
      who were drinking or aged <60. The haplotypes VDR
      Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study
      demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis
      of gastric cardiac adenocarcinoma, especially increased the risk in the younger
      and alcohol drinking Chinese population.

PMID- 28489591
TI  - Molecular characterization of circulating tumor cells from patients with
      metastatic breast cancer reflects evolutionary changes in gene expression under
      the pressure of systemic therapy.
AB  - Resistance to systemic therapy is a major problem in metastatic breast cancer
      (MBC) that can be explained by initial tumor heterogeneity as well as by
      evolutionary changes during therapy and tumor progression. Circulating tumor
      cells (CTCs) detected in a liquid biopsy can be sampled and characterized
      repeatedly during therapy in order to monitor treatment response and disease
      progression.Our aim was to investigate how CTC derived gene expression of
      treatment predictive markers (ESR1/HER2) and other cancer associated markers
      changed in patient blood samples during six months of first-line systemic
      treatment for MBC. CTCs from 36 patients were enriched using CellSearch (Janssen
      Diagnostics) and AdnaTest (QIAGEN) before gene expression analysis was performed
      with a customized gene panel (TATAA Biocenter).Our results show that antibodies
      against HER2 and EGFR were valuable to isolate CTCs unidentified by CellSearch
      and possibly lacking EpCAM expression. Evaluation of patients with clinically
      different breast cancer subgroups demonstrated that gene expression of treatment
      predictive markers changed over time. This change was especially prominent for
      HER2 expression.In conclusion, we found that changed gene expression during first
      line systemic therapy for MBC could be a possible explanation for treatment
      resistance. Characterization of CTCs at several time-points during therapy could
      be informative for treatment selection.

PMID- 28489596
TI  - Lymph nodes ratio based nomogram predicts survival of resectable gastric cancer
      regardless of the number of examined lymph nodes.
AB  - To develop a nomogram to predict the prognosis of gastric cancer patients on the
      basis of metastatic lymph nodes ratio (mLNR), especially in the patients with
      total number of examined lymph nodes (TLN) less than 15. The nomogram was
      constructed based on a retrospective database that included 2,205 patients
      underwent curative resection in Cancer Center, Sun Yat-sen University (SYSUCC).
      Resectable gastric cancer (RGC) patients underwent curative resection before
      December 31, 2008 were assigned as the training set (n=1,470) and those between
      January 1, 2009 and December 31, 2012 were selected as the internal validation
      set (n=735). Additional external validations were also performed separately by an
      independent data set (n=602) from Jiangxi Provincial Cancer Hospital (JXCH) in
      Jiangxi, China and a data set (n=3,317) from the Surveillance, Epidemiology, and
      End Results (SEER) database. The Independent risk factors were identified by
      Multivariate Cox Regression. In the SYSUCC set, TNM (Tumor-node-metastasis) and
      TRM-based (Tumor-Positive Nodes Ratio-Metastasis) nomograms were constructed
      respectively. The TNM-based nomogram showed better discrimination than the AJCC
      TNM staging system (C-index: 0.73 versus 0.69, p<0.01). When the mLNR was
      included in the nomogram, the C-index increased to 0.76. Furthermore, the C-index
      in the TRM-based nomogram was similar between TLN >=16 (C-index: 0.77) and TLN
      <=15 (C-index: 0.75). The discrimination was further ascertained by internal and
      external validations. We developed and validated a novel TRM-based nomogram that
      provided more accurate prediction of survival for gastric cancer patients who
      underwent curative resection, regardless of the number of examined lymph nodes.

PMID- 28489599
TI  - Association between the p.V37I variant of GJB2 and hearing loss: a pedigree and
      meta-analysis.
AB  - Pathogenic variants in the gap junction protein beta-2 (GJB2) gene are the most
      common cause of hearing loss. Of these, the p.V37I variant of GJB2 has a high
      allele frequency (up to 10%) in East Asians. Characterization of the phenotypic
      spectrum associated with p.V37I, as well as the role of this variant in the onset
      of hearing loss could have a remarkable effect on future diagnostic strategies.
      Here, we performed a pedigree analysis of unrelated families exhibiting various
      hearing phenotypes, and then conducted a meta-analysis to comprehensively assess
      the association between the p.V37I and the risk of hearing loss. Pedigree
      analyses showed that both homozygous p.V37I variants, as well as compound
      heterozygous p.V37I with other GJB2 pathogenic variants, contributed to various
      phenotypes of hearing loss. Meanwhile, meta-analysis demonstrated that, compared
      with those in the wild type group, both p.V37I homozygotes and compound
      heterozygous p.V37I variants were at significantly higher risk of developing
      hearing loss (odds ratios = 7.14 and 3.63; 95% confidence intervals = 3.01-16.95
      and 1.38-9.54, respectively). Conversely, heterozygous p.V37I variants alone did
      not increase the risk of hearing loss. Given the high allele carriage rate of
      p.V37I (up to 10%) within the general population, our work not only provides
      information that might influence future genetic screening policies, but also
      offers insight into clinical risk evaluation and genetic counseling regarding
      hearing loss.

PMID- 28489600
TI  - Oleate-induced PTX3 promotes head and neck squamous cell carcinoma metastasis
      through the up-regulation of vimentin.
AB  - The association between metabolic diseases and the risk of developing cancer is
      emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia
      associated tumor metastasis remains unknown. In this study, we found that oleate
      induced PTX3 expression and secretion through the activation of Akt/NF-kappaB
      pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF
      kappaB was essential for the oleate-induced stabilization of PTX3 mRNA. In
      addition, both the depletion of PTX3 and the inhibition of NF-kappaB
      significantly inhibited oleate-induced tumor cell migration and invasion. The
      enhancement of binding between tumor and endothelial cells was observed in oleate
      treated cells but not in the depletion and neutralization of PTX3 with siPTX3 and
      anti-PTX3 antibodies, respectively. The levels of oleate-induced epithelial
      mesenchymal transition (EMT) markers, such as vimentin and MMP-3, were
      significantly reduced in PTX3-depleted cells. Knocking down vimentin also
      repressed oleate-induced HNSCC invasion. Furthermore, the depletion of PTX3
      blocked the oleate-primed metastatic seeding of tumor cells in the lungs. These
      results demonstrate that oleate enhances HNSCC metastasis through the
      PTX3/vimentin signaling axes. The inhibition of PTX3 could be a potential
      strategy for the treatment of dyslipidemia-mediated HNSCC metastasis.

PMID- 28489602
TI  - Elevated serum growth differentiation factor 15 levels are associated with
      thyroid nodules in type 2 diabetes aged over 60 years.
AB  - In order to investigate whether serum growth differentiation factor 15 is
      associated with thyroid nodules in type 2 diabetes. We recruited 723 type 2
      diabetic patients aged over 30 years who attended the clinic of Endocrinology of
      Xinhua Hospital from January 2013 to January 2015. Thyroid nodule was diagnosed
      by thyroid ultrasonographic examination. Serum growth differentiation factor 15,
      thyroid function, thyroid autoantibodies, thyroglobulin and other biochemical
      indicators were measured and compared between thyroid nodule positive and
      negative groups. We found that overall, serum growth differentiation factor 15
      levels were significantly higher in subjects with thyroid nodules compared with
      nodule negative subjects (181.76+/-98.49 pg/ml vs. 162.32+/-83.63 pg/ml, p<0.05),
      and this was influenced by age. In the patients over 60 years, this difference
      became more significant (211.23+/-103.66 pg/ml vs. 177.38+/-85.51 pg/ml, p<0.01),
      but in patients under 60 years, there was no difference between the two groups.
      Multivariate logistic regression analysis showed that serum growth
      differentiation factor 15 levels were independently associated with thyroid
      nodule in diabetic patients over 60 years (P <0.001). After multiple adjustments,
      the odds ratios were substantially higher for thyroid nodule (odds ratio 2.63,
      95% confidence interval 1.30-5.13, p<0.01) in the highest growth differentiation
      factor 15 quartile compared to those in the lowest quartile in patients over 60
      years. In conclusion, serum growth differentiation factor 15 is increased
      significantly in subjects with thyroid nodules in type 2 diabetic patients aged
      over 60 years.

PMID- 28489603
TI  - 18F-fluorodeoxyglucose uptake predicts PKM2 expression in lung adenocarcinoma.
AB  - Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is
      widely used in the management of lung adenocarcinoma. Pyruvate kinase M2 (PKM2)
      plays a key role in glycolysis. We therefore investigated whether PKM2 expression
      affects 18F-FDG uptake in a retrospective analysis of 76 patients who underwent
      18F-FDG PET/computed tomography (CT) scans for staging before surgical resection.
      We found that PKM2 expression was higher in tumors than peritumoral tissue (p <
      0.05). Patients with high PKM2 expression had reduced overall (p < 0.05) and
      disease-free (p < 0.05) survival as compared to those with low PKM2 expression.
      Comparison of the primary tumor maximum standardized uptake value (SUVmax)
      between patients with high and low PKM2 expression revealed that the SUVmax was
      higher in primary tumors with high PKM2 expression than low PKM2 expression (p <
      0.05). Multivariate analysis confirmed the association between SUVmax and PKM2
      expression (p < 0.05). PKM2 status was predicted with 81.6% accuracy when the
      SUVmax cutoff value of 6.4. Thus,18F-FDG PET/CT is predictive of the PKM2 status
      in lung adenocarcinoma patients and could aid in determining therapeutic
      strategies.

PMID- 28489604
TI  - Prevalence of primary cardiac tumor malignancies in retrospective studies over
      six decades: a systematic review and meta-analysis.
AB  - The incidence of patients diagnosed with primary malignant cardiac tumors (PMCTs)
      has increased greatly in the past few decades. Whether this rising prevalence is
      due to overdiagnosis or an increased malignancy rate of primary cardiac tumors
      (PCTs) remains unclear. Therefore, we performed a systematic review and meta
      analysis of published retrospective studies to determine whether the malignancy
      rate has been increasing over time. Published studies containing relevant data
      between 1956 and 2014 were evaluated. Two authors searched for all retrospective
      studies that included patients diagnosed with PCT and PMCT. Two other
      investigators independently extracted the data, and discrepancies were resolved
      by consensus. A random-effects meta-analysis model and cumulative meta-analysis
      model were used to evaluate the pooled prevalence and trend of dynamic change in
      PCT malignancies. The effects of time, study period and sample size were studied
      using a logit-linear regression model with robust error variance and a time
      variable. Thirty-eight studies involving 5,586 patients were analyzed. The pooled
      prevalence of PMCT among the patients diagnosed with PCT was 9.9% (95% CI, 8.4%
      to 11.4%) (I2=70%; P< 0.001), and this prevalence has been stable since around
      2003. In the regression model, the malignancy odds ratio remained stable from
      1975 onward, and no time effect was observed. Our study confirms that PMCT is
      uncommon, and the prevalence of PCT malignancies remained stable in the past few
      decades. The clinically observed increase in incidence is unlikely to reflect a
      true population-level increase in tumorigenesis. This result strongly suggests
      that the observed increase in incidence of PMCT most likely reflects increased
      diagnostic detection over time.

PMID- 28489605
TI  - Genetic rearrangements result in altered gene expression and novel fusion
      transcripts in Sezary syndrome.
AB  - Sezary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma
      variant. Molecular pathogenesis of SS is still unclear despite many studies on
      genetic alterations, gene expression and epigenetic regulations. Through whole
      genome and transcriptome next generation sequencing nine Sezary syndrome patients
      were analyzed in terms of copy number variations and rearrangements affecting
      gene expression. Recurrent copy number variations were detected within 8q (MYC,
      TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1),
      but no recurrent rearrangements were identified. However, expression of five
      genes involved in rearrangements (TMEM244, EHD1, MTMR2, RNF123 and TOX) was
      altered in all patients. Fifteen rearrangements detected in Sezary syndrome
      patients and SeAx resulted in an expression of new fusion transcripts, nine of
      them were in frame (EHD1-CAPN12, TMEM66-BAIAP2, MBD4-PTPRC, PTPRC-CPN2, MYB
      MBNL1, TFG-GPR128, MAP4K3-FIGLA, DCP1A-CCL27, MBNL1-KIAA2018) and five resulted
      in ectopic expression of fragments of genes not expressed in normal T-cells
      (BAIAP2, CPN2, GPR128, CAPN12, FIGLA). Our results not only underscored the
      genomic complexity of the Sezary cancer cell genome but also showed an unpreceded
      large variety of novel gene rearrangements resulting in fusions transcripts and
      ectopically expressed genes.

PMID- 28489606
TI  - Pantoprazole blocks the JAK2/STAT3 pathway to alleviate skeletal muscle wasting
      in cancer cachexia by inhibiting inflammatory response.
AB  - OBJECTIVE: Cancer cachexia is often present in patients with advanced malignant
      tumors, and the subsequent body weight reduction results in poor quality of life.
      However, there has been no progress in developing effective clinical therapeutic
      strategies for skeletal muscle wasting in cancer cachexia. Herein, we explored
      the functions of pantoprazole on cancer cachexia skeletal muscle wasting.
      METHODS: The mouse colon adenocarcinoma cell line C26 was inoculated in the right
      forelimb of male BALB/C mice to establish a cancer cachexia model. The animals
      were treated with or without different concentrations of pantoprazole orally, and
      the body weight, tumor growth, spontaneous activity, and muscle functions were
      determined at various time points. Two weeks later, the levels of serum IL-6 and
      TNF-alpha, the mRNA levels of gastrocnemius JAK2 and STAT3, and the expression
      levels of p-JAK2, p-STAT3, Fbx32, and MuRF1 were examined with ELISA assay, qRT
      PCR assay, and Western blotting, respectively. Further studies were performed to
      assess the levels of Fbx32 and MuRF1 expression and morphological changes.
      RESULTS: Pantoprazole can alleviate cancer cachexia-induced body weight reduction
      and inhibit skeletal muscle wasting in a dose-dependent manner. Our results
      indicated that pantoprazole treatment can decrease the levels of serum IL-6 and
      TNF-alpha (56.3% and 67.6%, respectively), and inhibit the activation of the
      JAK2/STAT3 signaling pathway. Moreover, the expression levels of MuRF1 and Fbx32
      were also suppressed after pantoprazole treatment. CONCLUSION: Our findings
      suggested that pantoprazole can alleviate cancer cachexia skeletal muscle wasting
      by inhibiting the inflammatory response and blocking the JAK2/STAT3 or ubiquitin
      proteasome pathway.

PMID- 28489607
TI  - Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis
      induction of colorectal cancer cells.
AB  - Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer
      L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in
      vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against
      the tumor-associated antigen Her2, TSA treatment did not significantly increase
      the level of Her2-specific CTL response compared to that with vehicle treatment.
      However, there was a significant increase in the level of TNF-alpha mRNA in tumor
      tissue and Her2-specific Ab (antibody) production. More importantly, we found
      that TSA overcomes the tumor-associated immunosuppressive microenvironment by
      reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived
      suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated
      Her2/CT26 cells, based on the increased level of the mammalian autophagy protein
      LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5'
      AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of
      rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal
      protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated
      AMPK activation and inhibition of mTORC1 pathway might be associated with
      autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred
      by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double
      positive results, and TUNEL-positive cells. Finally, we found that the combined
      treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a
      greater extent than docetaxel alone. Therefore, we propose the use of TSA for
      supplementary anticancer therapy to support anti-neoplastic drugs, such as
      docetaxel, by inducing apoptosis in cancer cells and resulting in the induction
      of neighborhood anti-cancer immunity.

PMID- 28489608
TI  - Simulation study comparing the helmet-chin PET with a cylindrical PET of the same
      number of detectors.
AB  - There is a growing interest in developing brain PET scanners with high
      sensitivity and high spatial resolution for early diagnosis of neurodegenerative
      diseases and studies of brain functions. Sensitivity of the PET scanner can be
      improved by increasing the solid angle. However, conventional PET scanners are
      designed based on a cylindrical geometry, which may not be the most efficient
      design for brain imaging in terms of the balance between sensitivity and cost. We
      proposed a dedicated brain PET scanner based on a hemispheric shape detector and
      a chin detector (referred to as the helmet-chin PET), which is designed to
      maximize the solid angle by increasing the number of lines-of-response in the
      hemisphere. The parallax error, which PET scanners with a large solid angle tend
      to have, can be suppressed by the use of depth-of-interaction detectors. In this
      study, we carry out a realistic evaluation of the helmet-chin PET using Monte
      Carlo simulation based on the 4-layer GSO detector which consists of a 16  *  16 
      *  4 array of crystals with dimensions of 2.8  *  2.8  *  7.5 mm3. The purpose of
      this simulation is to show the gain in imaging performance of the helmet-chin PET
      compared with the cylindrical PET using the same number of detectors in each
      configuration. The sensitivity of the helmet-chin PET evaluated with a
      cylindrical phantom has a significant increase, especially at the top of the
      (field-of-view) FOV. The peak-NECR of the helmet-chin PET is 1.4 times higher
      compared to the cylindrical PET. The helmet-chin PET provides relatively low
      noise images throughout the FOV compared to the cylindrical PET which exhibits
      enhanced noise at the peripheral regions. The results show the helmet-chin PET
      can significantly improve the sensitivity and reduce the noise in the
      reconstructed images.

PMID- 28489609
TI  - Heart rate-based window segmentation improves accuracy of classifying
      posttraumatic stress disorder using heart rate variability measures.
AB  - OBJECTIVE: Heart rate variability (HRV) characterizes changes in autonomic
      nervous system function and varies with posttraumatic stress disorder (PTSD). In
      this study we developed a classifier based on heart rate (HR) and HRV measures,
      and improved classifier performance using a novel HR-based window segmentation.
      APPROACH: Single-channel ECG data were collected from 23 subjects with current
      PTSD, and 25 control subjects with no history of PTSD over 24 h. RR intervals
      were derived from these data, cleaned, and used to calculate HR and HRV metrics.
      These metrics were used as features in a logistic regression classifier.
      Performance was assessed via repeated random sub-sampling validation. To reduce
      noise and activity-related effects, we calculated features from five non
      overlapping ten-minute quiescent segments of RR intervals defined by lowest HR,
      as well as random ten-minute segments as a control. MAIN RESULTS: Using a
      combination of the four most predictive features derived from quiescent segments
      we achieved a median area under the receiver operating curve (AUC) of 0.86 on out
      of-sample test set data. This was significantly higher than the AUC using 24 h of
      data (0.72) or random segments (0.67). SIGNIFICANCE: These results demonstrate
      our segmentation approach improves the classification of PTSD from HR and HRV
      measures, and suggest the potential for tracking PTSD illness severity via
      objective physiological monitoring. Future studies should prospectively evaluate
      if classifier output changes significantly with worsening or effective treatment
      of PTSD.

PMID- 28489610
TI  - Invasive and noninvasive means of measuring intracranial pressure: a review.
AB  - : Measurement of intracranial pressure (ICP) can be invaluable in the management
      of critically ill patients. Cerebrospinal fluid is produced by the choroid plexus
      in the brain ventricles (a set of communicating chambers), after which it
      circulates through the different ventricles and exits into the subarachnoid space
      around the brain, where it is reabsorbed into the venous system. If the fluid
      does not drain out of the brain or get reabsorbed, the ICP increases, which may
      lead to brain damage or death. ICP elevation accompanied by dilatation of the
      cerebral ventricles is termed hydrocephalus, whereas ICP elevation accompanied by
      normal or small ventricles is termed idiopathic intracranial hypertension.
      OBJECTIVE: We performed a comprehensive literature review on how to measure ICP
      invasively and noninvasively. APPROACH: This review discusses the advantages and
      disadvantages of current invasive and noninvasive approaches. MAIN RESULTS:
      Invasive methods remain the most accurate at measuring ICP, but they are prone to
      a variety of complications including infection, hemorrhage and neurological
      deficits. Ventricular catheters remain the gold standard but also carry the
      highest risk of complications, including difficult or incorrect placement. Direct
      telemetric intraparenchymal ICP monitoring devices are a good alternative.
      Noninvasive methods for measuring and evaluating ICP have been developed and
      classified in five broad categories, but have not been reliable enough to use on
      a routine basis. These methods include the fluid dynamic, ophthalmic, otic, and
      electrophysiologic methods, as well as magnetic resonance imaging, transcranial
      Doppler ultrasonography (TCD), cerebral blood flow velocity, near-infrared
      spectroscopy, transcranial time-of-flight, spontaneous venous pulsations, venous
      ophthalmodynamometry, optical coherence tomography of retina, optic nerve sheath
      diameter (ONSD) assessment, pupillometry constriction, sensing tympanic membrane
      displacement, analyzing otoacoustic emissions/acoustic measure, transcranial
      acoustic signals, visual-evoked potentials, electroencephalography, skull
      vibrations, brain tissue resonance and the jugular vein. SIGNIFICANCE: This
      review provides a current perspective of invasive and noninvasive ICP
      measurements, along with a sense of their relative strengths, drawbacks and areas
      for further improvement. At present, none of the noninvasive methods demonstrates
      sufficient accuracy and ease of use while allowing continuous monitoring in
      routine clinical use. However, they provide a realizable ICP measurement in
      specific patients especially when invasive monitoring is contraindicated or
      unavailable. Among all noninvasive ICP measurement methods, ONSD and TCD are
      attractive and may be useful in selected settings though they cannot be used as
      invasive ICP measurement substitutes. For a sufficiently accurate and universal
      continuous ICP monitoring method/device, future research and developments are
      needed to integrate further refinements of the existing methods, combine
      telemetric sensors and/or technologies, and validate large numbers of clinical
      studies on relevant patient populations.

PMID- 28489611
TI  - FDG PET/CT in Aortic Valve Bioprosthesis Infection.
AB  - A 62-year-old man presented with persistent fever, weakness, and retrosternal
      pain 3 years after aortic valve bioprosthesis (AVR). His white blood cell count
      was 11,000/MUL and C-reactive protein was 13.6 mg/dL. Consecutive blood cultures
      isolated Staphylococcus epidermidis and capitis. Transesophageal echocardiography
      demonstrated small aortic valve prosthesis vegetation. F-FDG PET/CT revealed
      prominent AVR activity, SUVmax = 12.2. He was treated with daptomycin, meropenem,
      and gentamicin for 1 month and followed by daptomycin and carbapenem for 3
      months. Follow-up F-FDG PET/CT at 6 months demonstrated complete clearing of AVR
      activity associated with full asymptomatic recovery.

PMID- 28489612
TI  - Correlation between ambulatory blood pressure variability and vasodilator
      function in middle-aged normotensive individuals.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      ambulatory blood pressure variability and vasodilator function in a cohort of
      normotensive middle-aged individuals. PARTICIPANTS AND METHODS: This was a cross
      sectional study of 285 randomly selected 40-59-year-old normotensive participants
      who underwent 24-h ambulatory blood pressure monitoring and brachial artery
      ultrasound assessment. Systolic and diastolic blood pressure variability (BPV) of
      24-h, daytime, and night-time were calculated using the coefficients of variation
      (CV) and the average real variability (ARV) index. Brachial arterial endothelium
      dependent vasodilation (EDD) was assessed in response to increased flow and
      endothelium-independent vasodilation (EID) was assessed in response to
      nitroglycerin. Relationships were explored using univariate and multivariate
      linear regression. RESULTS: The EDD were negatively associated with the CV of 24
      h systolic blood pressure (SBP), the ARV of 24-h SBP, and diastolic blood
      pressure (DBP) in univariate analysis. However, the CV and ARV of 24-h SBP
      remained associated independently with % EDD in multivariate analysis. In
      addition, the mean levels of 24-h SBP and DBP, the CV of 24-h SBP and DBP, the
      ARV of 24-h SBP and DBP, the CV of daytime SBP, and the ARV of daytime DBP were
      all associated with % EID. However, in a multiple linear regression model,
      adjusting for covariates, only the CV and ARV of 24-h SBP, and the ARV of 24-h
      DBP were correlated negatively but weakly with % EID. CONCLUSION: Our results
      indicated that a higher 24-h BPV was associated independently with decreased
      endothelial-dependent and endothelial-independent vasodilator functions in a
      middle-aged normotensive population. Although 24-h BPV was associated with
      vasodilator function, relationships were attenuated after adjusting for
      covariates.

PMID- 28489613
TI  - The effect of back and feet support on oscillometric blood pressure measurements.
AB  - BACKGROUND/OBJECTIVE: Recommendations to support the back and feet during blood
      pressure (BP) measurement are not always followed in clinical practice. Our
      objective was to determine to what extent back and feet support affects mean
      oscillometric BP measurements. PARTICIPANTS AND METHODS: Eighty-five consecutive,
      consenting participants 18 years or older with systolic BP readings 80-220 mmHg
      and diastolic BP readings 50-120 mmHg and arm circumferences of 25-43 cm were
      recruited. BP was measured using an Omron HEM 907 oscillometric device. Back and
      feet support were examined independently. First, while the feet were supported,
      two sets of three BP readings were taken in random order: one with the back
      supported and one with the back unsupported. Next, with the back supported, two
      sets of three BP readings were taken in random order: one with the feet dangling
      and one with feet supported. RESULTS: The mean age of the participants was 52.0+/
      20.7 years and the mean arm circumference was 31.0+/-3.2 cm; 62% were women and
      49% had hypertension. The mean BP levels with the back unsupported were slightly
      higher than those with the back supported (119.8+/-15.5/69.9+/-8.9 vs. 119.2+/
      16.4/68.2+/-8.8 mmHg; difference of 0.7+/-4.9/1.8+/-3.0; P=0.21 for systolic and
      <0.0001 for diastolic comparisons). The mean BP levels with feet dangling were
      slightly lower than with feet supported (120.3+/-16.3/72.6+/-8.9 vs. 121.2+/
      16.1/72.9+/-8.6 mmHg; difference of -0.9+/-4.1/-0.3+/-2.8; P=0.04 for systolic
      and <0.36 for diastolic comparisons). Systolic BP differences were greater than
      or equal to 5 mmHg in 34% (back phase) and 23% (feet phase) of the participants.
      CONCLUSION: Provision of back and feet support has a small effect on the mean
      oscillometric BP. The magnitude of effect is greatest on diastolic BP when the
      back is unsupported.

PMID- 28489614
TI  - Validation of Innovative Techniques for Monitoring Nociception during General
      Anesthesia: A Clinical Study Using Tetanic and Intracutaneous Electrical
      Stimulation.
AB  - BACKGROUND: This study compares the analgesic indices Analgesia Nociception Index
      (heart rate variability), Surgical Pleth Index (photoplethysmography), and
      pupillary dilatation, to heart rate, mean arterial pressure, and bispectral
      index, with regard to diagnostic accuracy and prediction probability for
      nociceptive response. The primary endpoint was the correlation between Delta
      values and the remifentanil dose administered. METHODS: We anesthetized 38
      patients with propofol and increasing doses of remifentanil and applied
      standardized tetanic and intracutaneous electrical painful stimulations on each
      analgesic level. Baseline and Delta values of the Analgesia Nociception Index,
      the Surgical Pleth Index, pupillary dilatation, heart rate, mean arterial
      pressure, and bispectral index and their relation to remifentanil doses were
      analyzed by receiver operating characteristic curves, prediction probability
      (PK), and mixed-model analysis. RESULTS: Under propofol sedation, sensitivity and
      specificity of the Analgesia Nociception Index (PK = 0.98), the Surgical Pleth
      Index (PK = 0.87), and pupillary dilatation (PK = 0.98) for detecting both
      painful stimulations were high compared to heart rate (PK = 0.74), mean arterial
      pressure (PK = 0.75), and bispectral index (PK = 0.55). Baseline values had
      limited prediction probability toward the nociceptive response (Analgesia
      Nociception Index: PK = 0.7; Surgical Pleth Index: PK = 0.63; pupillary
      dilatation: PK = 0.67; and bispectral index: PK = 0.67). The remifentanil dose
      had an effect (P < 0.001) on all parameters except for bispectral index (P =
      0.216). CONCLUSIONS: The Analgesia Nociception Index, the Surgical Pleth Index,
      and pupillary dilatation are superior in detecting painful stimulations compared
      to heart rate and mean arterial pressure but had limited predictive value. These
      effects are attenuated by increasing dosages of remifentanil. Our data confirm
      that bispectral index is not a marker of analgesia.

PMID- 28489615
TI  - Report of two cases of acute cardiac adverse events in patients with colorectal
      carcinoma receiving oral capecitabine.
AB  - Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after
      oral administration, is metabolized to its active cytotoxic compound: 5
      fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a
      closely related fluorinated pyrimidine antagonist. In the present report, we
      report on two patients who were admitted to our department after being treated
      with oral capecitabine for colorectal carcinoma and developed symptoms and signs
      of acute myocardial infarction that resolved after appropriate treatment and
      monitoring. The above two cases are discussed in the context of fluoropyrimidine,
      5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature
      review of relevant cases and patient series reports is presented.

PMID- 28489617
TI  - Best Practices for Increasing Reading Compliance in Undergraduate Medical
      Education.

PMID- 28489616
TI  - Complete response to anti-PD-1 nivolumab in massive skin metastasis from
      melanoma: efficacy and tolerability in an elderly patient.
AB  - The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and
      effective treatment options with proven clinical benefits for patients affected
      by metastatic melanoma. The 30-40% of treated patients experience an objective
      tumour regression, with a significantly prolonged survival and an improved
      quality of life. Here, we report a case of a 75-year-old Caucasian woman affected
      by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced
      multiple relapses after surgery and repeated electrochemotherapy treatments. A
      poor response was observed after systemic therapy with ipilimumab, whereas a
      marked reduction in the lesion size was obtained during the treatment with
      nivolumab, with an objectively complete response after 6 months. Therapy was well
      tolerated, without immune-related side effects. During treatment, LDH levels
      decreased up to the standard values. Our experience confirms the good efficacy
      and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory
      massive skin lesions, also in elderly patients.

PMID- 28489618
TI  - Core Competencies or a Competent Core? A Scoping Review and Realist Synthesis of
      Invasive Bedside Procedural Skills Training in Internal Medicine.
AB  - PURPOSE: Invasive bedside procedures are core competencies for internal medicine,
      yet no formal training guidelines exist. The authors conducted a scoping review
      and realist synthesis to characterize current training for lumbar puncture,
      arthrocentesis, paracentesis, thoracentesis, and central venous catheterization.
      They aimed to collate how educators justify using specific interventions,
      establish which interventions have the best evidence, and offer directions for
      future research and training. METHOD: The authors systematically searched
      Medline, Embase, the Cochrane Library, and ERIC through April 2015. Studies were
      screened in three phases; all reviews were performed independently and in
      duplicate. The authors extracted information on learner and patient demographics,
      study design and methodological quality, and details of training interventions
      and measured outcomes. A three-step realist synthesis was performed to synthesize
      findings on each study's context, mechanism, and outcome, and to identify a
      foundational training model. RESULTS: From an initial 6,671 studies, 149 studies
      were further reduced to 67 (45%) reporting sufficient information for realist
      synthesis. Analysis yielded four types of procedural skills training
      interventions. There was relative consistency across contexts and significant
      differences in mechanisms and outcomes across the four intervention types. The
      medical procedural service was identified as an adaptable foundational training
      model. CONCLUSIONS: The observed heterogeneity in procedural skills training
      implies that programs are not consistently developing residents who are competent
      in core procedures. The findings suggest that researchers in education and
      quality improvement will need to collaborate to design training that develops a
      "competent core" of proceduralists using simulation and clinical rotations.

PMID- 28489619
TI  - Pediatric Resident Academic Projects While on Global Health Electives: Ten Years
      of Experience at the University of Minnesota.
AB  - PURPOSE: Many residency programs require residents to complete an academic
      project as part of a global health (GH) elective. However, there has been little
      description of the range of projects residents have pursued during GH electives
      or the extent to which these projects are consistent with proposed best
      practices. METHOD: The authors conducted a document review of 67 written
      summaries or copies of presentations of academic projects (hereafter, summaries)
      completed by pediatric and medicine-pediatric residents at the University of
      Minnesota while on GH electives from 2005 to 2015. Two authors independently
      coded each summary for the type of project completed; when the project idea was
      generated; explicit mention of a mentor from the home institution, host
      institution, or both; whether a needs assessment was conducted; and whether there
      were plans for sustainability. RESULTS: Most of the 67 projects were categorized
      into one of three project types: quality/process improvement (28 [42%]),
      education (18 [27%]), or clinical research (14 [21%]). Most summaries explicitly
      mentioned a mentor (45 [67%]), reported conducting a needs assessment (38 [57%]),
      and indicated sustainability plans (45 [67%]). Of the 42 summaries that indicated
      the timing of idea generation, 30 (71%) indicated the idea was developed after
      arriving at the host site. CONCLUSIONS: Residents undertook a wide range of
      academic projects during GH electives, most commonly quality/process improvement
      and education projects. The projects were largely aligned with best practices,
      with most summaries indicating the resident worked with a mentor, conducted a
      needs assessment, and made plans for sustainability.

PMID- 28489620
TI  - Adult desmoid tumors: biology, management and ongoing trials.
AB  - PURPOSE OF REVIEW: To summarize the current knowledge about the biology and
      clinical management of adult desmoid tumors. RECENT FINDINGS: In the past decade,
      we have learned that desmoid tumors are driven by alterations of the Wnt/APC/beta
      catenin pathway, sporadic desmoid tumors are associated with somatic mutations of
      CTNNB1, and germline mutations of APC and somatic mutations of CTNNB1 are
      probably mutually exclusive. One-third of desmoid tumors are misdiagnosed; a
      second pathological opinion is therefore of major importance for desmoid tumor.
      Surgery is no longer regarded as the cornerstone of desmoid tumors; several
      retrospective studies have demonstrated the safety of a 'wait and see' policy in
      sporadic abdominal wall desmoid tumor. Desmoid tumors is no longer regarded as an
      absolute contraindication for pregnancy. At least two new investigational drugs
      targeting the Wnt/APC/beta-catenin pathway are currently being developed.
      SUMMARY: The management of desmoid tumors requires multidisciplinary expertise by
      an experienced team. We must fully understand the physiopathology of the disease
      (factors influencing the natural history of the disease) and learn how to avoid
      desmoid tumors occurrence in patients with APC germline mutations, identify
      reliable prognostic/predictive factors and better assess the efficacy of systemic
      treatment.

PMID- 28489622
TI  - Periorbital Papular Amyloidosis.

PMID- 28489621
TI  - Own and partner pain intensity in older couples: longitudinal effects on
      depressive symptoms.
AB  - Chronic pain has been linked to depression among individuals and their partners.
      Yet, little is known about long-term mutual influences between pain intensity and
      depressive symptoms within couples as they age. Using a nationally representative
      U.S. sample of wives and husbands aged 50 and older (mean = 64.53, SD = 7.86),
      this study explored the links between own and partner pain intensity and
      depressive symptoms across an 8-year period. A total of 963 heterosexual married
      couples drawn from the Health and Retirement Study completed interviews
      biennially from 2006 to 2014. Dyadic growth curve models examined mutual
      associations within couples and controlled for sociodemographic characteristics,
      length of marriage, and marital quality, along with self-rated health, number of
      chronic health conditions, and functional disability. For wives and husbands,
      their own greater baseline pain intensity was significantly linked to their own
      higher levels of depressive symptoms. Unexpectedly, wives with greater baseline
      pain intensity reported decreases in their depressive symptoms over time. There
      were also partner effects such that husbands' greater pain intensity at baseline
      was associated with increases in wives' depressive symptoms over time. Findings
      highlight the importance of considering both individual and spousal associations
      between pain intensity and depressive symptoms in later life. Understanding how
      individual and couple processes unfold may yield critical insights for the
      development of intervention and prevention efforts to maintain mental health
      among older chronic pain patients and their spouses.

PMID- 28489623
TI  - Retinal and Choroidal Detachment in Antineutrophil Cytoplasmic Antibody
      Associated Scleritis and Retinal Vasculitis Mimicking Choroidal Tumor.

PMID- 28489624
TI  - Defining Quality of Rheumatologic Care: Mexico.
AB  - We present an overview of rheumatology practices in Mexico, describing the
      national health care system as segmented and fragmentary, with a population
      separated into 3 main categories, according to employment-based coverage and
      income level: (1) private sector, (2) Social Security System, and (3) public
      insurance subsector.The rheumatology practice in the public and private sectors
      are described. We estimate that between 85%-90% of Mexican rheumatologists have a
      mixed (public and private)-type practice. Payments to rheumatologists are not
      currently affected by quality and value metrics, with low penetrance of
      electronic health records. Recent changes and challenges to health insurance
      coverage are illustrated.

PMID- 28489625
TI  - The Disease of the Italian Poet Giacomo Leopardi (1798-1837): A Case of Juvenile
      Ankylosing Spondylitis in the 19th Century?
AB  - Some authors sustained that the pessimistic thought of the Italian writer and
      philosopher Giacomo Leopardi (1798-1837) may be attributed to his unhappy life,
      characterized by several health problems. His philosophical theories appear as
      the result of depressive and melancholic state, related to his precarious health
      conditions, so limiting their intrinsic values. Several authors formulated
      various hypotheses on the diseases that Leopardi suffered from and postulated
      different theories on the cause of his early death. This article assumed that
      Leopardi may have been affected by juvenile ankylosing spondylitis, conditioning
      spinal deformities, relapsing-remitting uveitis, urinary tract and bowel tract
      problems, and acute arthritis. Chest deformity, as a complication of juvenile
      ankylosing spondylitis, may have caused progressive cardiorespiratory failure,
      worsened by recurrent bronchial and pulmonary complications, until his death
      caused by acute right ventricular heart failure. The acknowledgment of a physical
      cause of Leopardi's disease contributes to reevaluate his "cosmic pessimism" as
      an original expression of his thought, so leading a general revaluation of the
      figure of one of the most important European thinkers of the 19th century.

PMID- 28489627
TI  - Radial Head Ingrowth Anatomic Implant Versus Smooth Stem Monoblock Implant in
      Acute Terrible Triad Injury: A Prospective Comparative Study.
AB  - OBJECTIVE: This study aimed to compare clinical outcomes and radiographic
      findings between patients who received 2 different implants (smooth-stemmed
      modular implant or an anatomic press-fit implant) on patients with acute terrible
      triad injuries. DESIGN: Prospective cohort. SETTING: Level II Trauma center,
      University hospital. PATIENTS/PARTICIPANTS: Thirty-four patients with an isolated
      terrible triad injury were divided into 2 study groups (n = 17 each) with
      different sets of radial head implants and followed for 2 years. A total of 14
      patients in each group (n = 28) completed the study. INTERVENTION: Group 1
      received a smooth-stemmed round modular monopolar implant. Group 2 received an in
      growth modular monopolar press-fit anatomic implant. MAIN OUTCOME MEASUREMENTS:
      Clinical outcomes were evaluated using the Visual Analog Scale, Mayo Index, and
      Disabilities of the Arm, Shoulder, and Hand (DASH) survey. Radiographs were
      evaluated for ectopic bone formation and loosening. RESULTS: No difference in
      clinical outcome when comparing range of motion and functionally scores between
      groups. Ectopic bone formation occurred equally with implants. Bone formation at
      the proximal radius under the implant occurred more in group 1 (85.7%), (P =
      0.046). Five press-fit stems had radiolucent lines at 2-year follow-up. Two were
      removed because of symptomatic loosening. CONCLUSIONS: Short-term outcomes for
      both implants showed to be equally effective treatment options. The in vitro
      biomechanical advantages of anatomic implants do not translate into short-term
      improved outcomes. Symptomatic aseptic loosening in anatomic implants is common.
      Bone formation at the proximal radial neck was observed more with smooth-stemmed
      implants; further studies should assess this findings and clinical implication.
      LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 28489628
TI  - Lengthening of newly formed humerus after autologous fibula graft transplantation
      following intercalary tumor resection.
AB  - Secondary limb lengthening after intercalary bone resection in pediatric patients
      is still challenging. After the resection, a free fibula autograft can be used to
      reconstruct the osseous gap. However, in particular in young pediatric patients,
      insufficient growth of the epiphyseal plate after transplantation may lead to a
      significant limb-length discrepancy (LLD). In this case, the autograft was used
      for limb lengthening. We report on the lengthening of a humerus regenerate after
      fibula autograft transplantation into a humeral defect in a pediatric/young
      adolescent patient. Because of LLD, she underwent callus distraction of the
      humerus regenerate after transplantation of a fibula autograft using a unilateral
      external fixator device. An 18-year-old female patient with status
      postintercalary proliferating chondroma resection (at the age of 7 years)
      required treatment for correction of a 13 cm humerus shortening. She reported no
      pain, had no functional limitations, and had a full range of motion of the
      shoulder and elbow joint. She complained about her short humerus and overall body
      scheme. A unilateral external fixator device for callus distraction was applied
      to the transplanted humerus regenerate after free fibula autograft
      transplantation. Bone lengthening was performed by distraction (2*0.5 mm/day).
      After 62 days and a lengthening of 6 cm in total, bone distraction was stopped
      mainly to avoid any complication. At this time, there was no limitation in the
      range of motion. No nerve palsy or other problems occurred at any time of the
      distraction. In pediatric patients, the transplantation of a fibula autograft is
      a well-established option to bridge an osseous gap after intercalary bone
      resection. This case report shows that even the humerus regenerate after fibula
      autograft transplantation has excellent potential for callotasis and bone
      remodeling and therefore bone lengthening in patients with LLD is an option even
      after transplantation of an autograft. This method provides a new therapeutic
      option for patients with LLD after fibula transplantation.

PMID- 28489629
TI  - Modulation of Isometric Quadriceps Strength in Soccer Players With Transcranial
      Direct Current Stimulation: A Crossover Study.
AB  - Vargas, VZ, Baptista, AF, Pereira, GOC, Pochini, AC, Ejnisman, B, Santos, MB,
      Joao, SMA, and Hazime, FA. Modulation of isometric quadriceps strength in soccer
      players with transcranial direct current stimulation: a crossover study. J
      Strength Cond Res 32(5): 1336-1341, 2018-The aim of this study was to evaluate
      the effect of transcranial direct current stimulation (tDCS) on the maximum
      isometric muscle contraction (MVIC) of the knee extensors in soccer players at
      the preprofessional level. Twenty female soccer players aged 15-17 years (mean =
      16.1; SD = 0.9) with 5.2 +/- 2.6 years of training were randomly divided into 2
      groups to receive either active or sham tDCS in a single session (2 mA; 0.057
      mA.cm). The MVIC of the knee extensors was evaluated in both lower limbs by
      manual dynamometry in 5 sets of contractions divided into 4 blocks: (a)
      prestimulation, (b) during tDCS, (c) 30 minutes after tDCS, and (d) 60 minutes
      after tDCS. After an interval of 7 days, the groups were evaluated again, and the
      type of initial stimulation was inverted between participants. The MVIC of the
      knee extensors increased significantly during active tDCS (dominant limb (DL) =
      0.4; IC = 0.1-0.8 N.Kg), 30 minutes after active tDCS (DL = 0.9; IC 0.4-1.4
      N.Kg), and 60 minutes after active tDCS (DL = 1.0; IC 0.3-1.6 N.Kg) but not for
      sham tDCS. Our conclusion was that tDCS temporarily increases isometric
      quadriceps strength in adolescent female soccer players, which may be useful for
      both strength training and rehabilitation.

PMID- 28489630
TI  - Effects of Incisional Negative-Pressure Wound Therapy on Primary Closed Defects
      after Superficial Circumflex Iliac Artery Perforator Flap Harvest: Randomized
      Controlled Study.

PMID- 28489631
TI  - Looking Beyond the Knife: Establishing a Framework for Micropigmentation
      following Breast Reconstruction.

PMID- 28489632
TI  - Comparison of Preoperative and Postoperative Lymphatic Function is Essential to
      Understand the Changes in Lymphatic Function.

PMID- 28489633
TI  - Reply: Comparison of Preoperative and Postoperative Lymphatic Function is
      Essential to Understand the Changes in Lymphatic Function.

PMID- 28489634
TI  - Reply: Effects of Negative-Pressure Wound Therapy on Primary Closed Defects after
      Superficial Circumflex Iliac Artery Perforator Flap Harvest: Randomized
      Controlled Study.

PMID- 28489635
TI  - Trends in sex differences in clinical characteristics, treatment strategies, and
      mortality in patients with ST-elevation myocardial infarction in Poland from 2005
      to 2011.
AB  - INTRODUCTION: During the last decade, there has been an increased awareness of
      sex differences in the clinical characteristics, management, and mortality in
      myocardial infarction. Many previous studies have found that women with ST
      elevation myocardial infarction (STEMI) have a poorer baseline risk profile, are
      less intensively treated, and have worse outcomes. OBJECTIVE: To evaluate whether
      sex disparities in STEMI have changed in recent years. METHODS: This is a
      retrospective analysis of data on 111 148 STEMI patients enrolled in the Polish
      Registry of Acute Coronary Syndromes between 2005 and 2011. Temporal trends in
      the clinical presentation, treatment strategies, and mortality rates between men
      and women are compared. RESULTS: Throughout the study, women were, on average,
      older than men, and more frequently presented with hypertension, diabetes, or
      obesity. These differences showed a tendency for narrowing. The percentage of
      smokers increased in both sexes. Despite a reduction in prehospital delays, they
      remained longer in women. Sex differences in prehospital cardiac arrest and
      cardiogenic shock at admission disappeared. In 2011, women were still less likely
      to undergo coronary angiography with subsequent revascularization, but it was
      mainly driven by patients older than 70 years of age who also had a higher in
      hospital mortality. Despite the greater relative risk reductions, the crude
      mortality rates remained significantly higher in women. Female sex was not an
      independent predictor of mortality. CONCLUSION: Sex differences in STEMI patients
      were narrowing from 2005 to 2011 in Poland. However, more attention needs to be
      focused on increasing smoking prevalence, the longer times from symptoms onset to
      hospital admission in women and the lower frequencies of the use of an invasive
      treatment strategy in older women, and their worse in-hospital outcomes.

PMID- 28489636
TI  - A selective approach to coronary revascularization among patients undergoing
      transcatheter aortic valve replacement.

PMID- 28489637
TI  - Pilot Study Comparing Closed Versus Open Tracheal Suctioning in Postoperative
      Neonates and Infants With Complex Congenital Heart Disease.
AB  - OBJECTIVES: To determine the hemodynamic effect of tracheal suction method in the
      first 36 hours after high-risk infant heart surgery on the PICU and to compare
      open and closed suctioning techniques. DESIGN: Pilot randomized crossover study.
      SETTING: Single PICU in United Kingdom. PARTICIPANTS: Infants undergoing surgical
      palliation with Norwood Sano, modified Blalock-Taussig shunt, or pulmonary artery
      banding in the first 36 hours postoperatively. INTERVENTIONS: Infants were
      randomized to receive open or closed (in-line) tracheal suctioning either for
      their first or second study tracheal suction in the first 36 hours
      postoperatively. MEASUREMENTS AND MAIN RESULTS: Twenty-four infants were enrolled
      over 18 months, 11 after modified Blalock-Taussig shunt, seven after Norwood
      Sano, and six after pulmonary artery banding. Thirteen patients received the open
      suction method first followed by the closed suction method second, and 11
      patients received the closed suction method first followed by the open suction
      method second in the first 36 hours after their surgery. There were statistically
      significant larger changes in heart rate (p = 0.002), systolic blood pressure (p
      = 0.022), diastolic blood pressure (p = 0.009), mean blood pressure (p = 0.007),
      and arterial saturation (p = 0.040) using the open suction method, compared with
      closed suctioning, although none were clinically significant (defined as
      requiring any intervention). CONCLUSIONS: There were no clinically significant
      differences between closed and open tracheal suction methods; however, there were
      statistically significant greater changes in some hemodynamic variables with open
      tracheal suctioning, suggesting that closed technique may be safer in children
      with more precarious physiology.

PMID- 28489638
TI  - Current Status of Cardiovascular Anesthesia in China.
AB  - High quality and safe cardiac anesthesia is a prerequisite for success in cardiac
      care. Cardiac surgery has developed rapidly over recent years in China. Because
      of language barriers, the current status of cardiac anesthesia in China is not
      well known to Western countries. To assess practice patterns, volume, workforce,
      and training requirements of Chinese cardiovascular anesthesiologists, we
      surveyed 92 major cardiovascular centers in China regarding their anesthesia
      practice, monitoring techniques, resources, staffing, and work hours. We aim to
      provide a review of the history, new developments, and a current cross section of
      cardiac anesthesia practice patterns in China. The goal is to allow Western
      readers to understand the unique achievements and challenges in Chinese
      cardiovascular anesthesiology, thus promoting further communications with Chinese
      cardiovascular anesthesiologists.

PMID- 28489639
TI  - Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O
      Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.
AB  - BACKGROUND: Morphine-6-O-sulfate (M6S) is a mixed MU/delta-opioid receptor (OR)
      agonist and potential alternative to morphine for treatment of chronic multimodal
      pain. METHODS: To provide more support for this hypothesis, the antinociceptive
      effects of M6S and morphine were compared in tests that access a range of pain
      modalities, including hot plate threshold (HPT), pinprick sensitivity threshold
      (PST) and paw pressure threshold tests. RESULTS: Acutely, M6S was 2- to 3-fold
      more potent than morphine in HPT and PST tests, specifically, derived from best
      fit analysis of dose-response relationships of morphine/M6S half-effective dose
      (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in
      HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies
      were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4).
      After 7 to 9 days of chronic treatment, tolerance developed to the
      antinociceptive effects of morphine, but not to M6S, in all 3 pain tests.
      Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects
      of M6S were not sensitive to kappa-OR antagonists. However, the delta-OR
      antagonist, naltrindole, blocked M6S-induced antinociception by 55% +/- 4% (95%
      CI, 39-75) in the HPT test, 94% +/- 4% (95% CI, 84-105) in the PST test, and 5%
      +/- 17% (95% CI, -47 to 59) or 51% +/- 14% (95% CI, 14-84; 6 rats per each group)
      in the paw pressure threshold test when examined acutely or after 7 days of
      chronic treatment, respectively. CONCLUSIONS: Activity via delta-ORs thus appears
      to be an important determinant of M6S action. M6S also exhibited favorable
      antinociceptive and tolerance profiles compared with morphine in 3 different
      antinociceptive assays, indicating that M6S may serve as a useful alternative for
      rotation in morphine-tolerant subjects.

PMID- 28489640
TI  - Little Black Boxes: Noncardiac Implantable Electronic Medical Devices and Their
      Anesthetic and Surgical Implications.
AB  - Implanted electronic medical devices. or stimulators such as pacemakers and nerve
      stimulators have grown enormously in diversity and complexity over recent
      decades. The function and potential interaction of these devices with the
      perioperative environment is of increasing concern for anesthesiologists and
      surgeons. Because of the innate electromagnetic environment of the hospital
      (operating room, gastrointestinal procedure suite, and imaging suite), implanted
      device malfunction, reprogramming, or destruction may occur and cause physical
      harm (including nerve injury, blindness, deafness, burn, stroke, paralysis, or
      coma) to the patient. It is critical for the anesthesiologist and surgeon to be
      aware of the function and interaction of implanted devices, both with other
      implanted devices and procedures (such as magnetic resonance imaging and
      cardioversion) in the hospital environment. Because of these interactions, it is
      imperative that proper device function is assessed when the surgical procedure is
      complete. This review article will discuss these important issues for 12
      different types of "little black boxes," or noncardiac implantable electronic
      medical devices.

PMID- 28489642
TI  - Pupillary Reflex for Evaluation of Thoracic Paravertebral Block: A Prospective
      Observational Feasibility Study.
AB  - BACKGROUND: Although thoracic paravertebral block (TPVB) is recommended in major
      breast surgery, there is no gold standard to assess the success of TPVB.
      Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after
      a noxious stimulus. The objective was to evaluate the feasibility of recording
      the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB.
      METHODS: This prospective, observational, single-center study included 32
      patients requiring breast surgery under general anesthesia and TPVB. TPVB was
      performed before surgery under ultrasound guidance with 20 mL of 0.75%
      ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was
      recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the
      anterior chest wall. The PDR was defined as the maximal increase in pupil
      diameter after a standardized noxious stimulus, expressed as a percentage of the
      initial pupil diameter. The PDR was recorded twice in the same eye for each
      patient after a stimulus on both the TPVB and the control sides. Postoperative
      pain scores were recorded in a postanesthesia care unit. The primary outcome was
      the difference between the PDR on the TPVB and the control sides. RESULTS: The
      median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%
      66%) on the control side. There was a significant difference in the PDR between
      the TPVB and the control sides with a Hodges-Lehmann estimate of absolute
      difference of 37% points (95% confidence interval, 25-52, P < .001). Median
      postoperative pain scores (interquartile range) in the postanesthesia care unit
      were 1 (0-3) at rest and 1 (0-3) during mobilization, respectively. There was a
      linear correlation between maximal postoperative pain scores and the PDR on the
      TPVB side with a Pearson's correlation coefficient r = 0.40 (95% confidence
      interval, 0.06-0.66, P = .02). No correlation was found between the number of
      blocked dermatomes and maximal postoperative pain scores (P = .06) or between the
      number of blocked dermatomes and the PDR on the TPVB side (P = .15). CONCLUSIONS:
      This proof-of-concept trial suggests that the effect of TPVB could be monitored
      by measuring the PDR after anterior chest wall stimulation in the dermatome of
      interest.

PMID- 28489641
TI  - Differences in Blood Pressure in Infants After General Anesthesia Compared to
      Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).
AB  - BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a
      prospective randomized, controlled, multisite, trial designed to assess the
      influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A
      secondary aim obtained from the blood pressure data of the GAS trial is to
      compare rates of intraoperative hypotension after anesthesia and to identify risk
      factors for intraoperative hypotension. METHODS: A total of 722 infants <=60
      weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to
      either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria
      included risk factors for adverse neurodevelopmental outcome and infants born at
      <26 weeks of gestation. Moderate hypotension was defined as mean arterial
      pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial
      pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The
      primary outcome was any measured hypotension <35 mm Hg from start of anesthesia
      to leaving the operating room. This analysis is reported primarily as intention
      to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA
      compared with RA predicting any measured hypotension of <35 mm Hg from the start
      of anesthesia to leaving the operating room was 2.8 (confidence interval [CI],
      2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per
      protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and
      16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable
      modeling, group assignment (GA versus RA), weight at the time of surgery, and
      minimal intraoperative temperature were risk factors for hypotension.
      Interventions for hypotension occurred more commonly in the GA group compared
      with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA
      reduces the incidence of hypotension and the chance of intervention to treat it
      compared with sevoflurane anesthesia in young infants undergoing inguinal hernia
      repair.

PMID- 28489643
TI  - Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter
      Emergency Medical Service.
AB  - BACKGROUND: Pain is frequently encountered in the prehospital setting and needs
      to be treated quickly and sufficiently. However, incidences of insufficient
      analgesia after prehospital treatment by emergency medical services are reported
      to be as high as 43%. The purpose of this analysis was to identify modifiable
      factors in a specific emergency patient cohort that influence the pain suffered
      by patients when admitted to the hospital. METHODS: For that purpose, this
      retrospective observational study included all patients with significant pain
      treated by a Swiss physician-staffed helicopter emergency service between April
      and October 2011 with the following characteristics to limit selection bias: Age
      > 15 years, numerical rating scale (NRS) for pain documented at the scene and at
      hospital admission, NRS > 3 at the scene, initial Glasgow coma scale > 12, and
      National Advisory Committee for Aeronautics score < VI. Univariate and
      multivariable logistic regression analyses were performed to evaluate patient and
      mission characteristics of helicopter emergency service associated with
      insufficient pain management. RESULTS: A total of 778 patients were included in
      the analysis. Insufficient pain management (NRS > 3 at hospital admission) was
      identified in 298 patients (38%). Factors associated with insufficient pain
      management were higher National Advisory Committee for Aeronautics scores, high
      NRS at the scene, nontrauma patients, no analgesic administration, and treatment
      by a female physician. In 16% (128 patients), despite ongoing pain, no analgesics
      were administered. Factors associated with this untreated persisting pain were
      short time at the scene (below 10 minutes), secondary missions of helicopter
      emergency service, moderate pain at the scene, and nontrauma patients. Sufficient
      management of severe pain is significantly better if ketamine is combined with an
      opioid (65%), compared to a ketamine or opioid monotherapy (46%, P = .007).
      CONCLUSIONS: In the studied specific Swiss cohort, nontrauma patients, patients
      on secondary missions, patients treated only for a short time at the scene before
      transport, patients who receive no analgesic, and treatment by a female physician
      may be risk factors for insufficient pain management. Patients suffering pain at
      the scene (NRS > 3) should receive an analgesic whenever possible. Patients with
      severe pain at the scene (NRS >= 8) may benefit from the combination of ketamine
      with an opioid. The finding about sex differences concerning analgesic
      administration is intriguing and possibly worthy of further study.

PMID- 28489644
TI  - An Open-Source Ultrasound Software for Diagnosis of Fistula Maturation.
AB  - Vascular access is essential for hemodialysis patients. The mature native
      arteriovenous fistula has been the preferred vascular access for hemodialysis,
      because it has greater longevity than synthetic grafts. However, once surgically
      created, fistulas often fail to develop (mature) into viable points of vascular
      access, requiring surgical or radiologic interventions before their use. Because
      maturation depends on vascular mechanics (e.g., distensibility and wall shear),
      we developed open-source ultrasound software to investigate these metrics
      clinically. We demonstrated in a single patient the ability of the software for
      consistent measurements from various locations within a cardiac cycle and between
      different cardiac cycles. We further assessed the ability of the software to
      identify changes in distensibility of a patient's fistula from 1 to 6 weeks
      postoperation. The routine frame rates of clinical machines demonstrated high
      fidelity tracking within cardiac cycles (coefficient of variation [CV] = 2.4% +/-
      0.011) and between cardiac cycles (CV = 2.4% +/- 0.004). The distensibility of
      the patient's fistula from 1 to 6 weeks postoperation increased from 4% to 7% in
      the arterial inflow and from 3% to 4% in the postarterial anastomotic segment
      (PAAS). In contrast, the distensibility of the outflow vein decreased from 4% to
      2%. These results corroborate that in addition to diameter changes, the
      mechanical properties of the vascular segments changed during fistula maturation.
      This demonstrates that our software-based approach may allow ultrasound-based
      mechanical measurements to become more accessible for wider clinical research.

PMID- 28489646
TI  - Aggressive Hydration With Lactated Ringer Solution in Prevention of
      Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.

PMID- 28489645
TI  - Portal Vein Thrombosis in Cirrhosis.
AB  - Portal vein thrombosis (PVT) in the cirrhotic population is a challenging
      clinical phenomenon requiring a nuanced management approach. Uncertainty exists
      regarding the clinical significance of PVT in the cirrhotic population because
      the data for PVT are based mainly on retrospective, small cohort studies.
      Therefore, strong recommendations regarding the optimal timing, modality, and
      duration of therapy for PVT in the cirrhotic population cannot be made. However,
      this review aims to summarize the current literature and provide stepwise
      guidance in diagnosing and managing PVT in patients with cirrhosis.

PMID- 28489647
TI  - Obesity/Bariatric Surgery and Crohn's Disease.
AB  - BACKGROUND: Crohn's disease (CD) following bariatric surgery has been previously
      described. It is not clear whether the clinical entity is due to rapid metabolism
      of fat, change in the bacterial milieu of the bowel, the loss of defense
      mechanisms of the stomach, or even a coincidence. OBJECTIVES: To present
      observations which might serve to sort out these various etiologies. DESIGN: We
      present 5 cases of colitis, ileocolitis or enteritis, some with fistula
      formation, with clinical onset following bariatric surgery and add these to the 7
      cases previously identified as CD reported elsewhere. We provide the clinical
      features of these 12 cases to reconcile with causative mechanisms. LIMITATIONS:
      It remains possible that the onset of CD (or other inflammatory bowel disease)
      precedes the bariatric surgery which then accelerates the clinical manifestations
      described. Furthermore, without controls the association could remain a
      coincidence. CONCLUSIONS: We review the evidence for release of proinflammatory
      cells and cytokines contained in fat following the bariatric surgery, and also
      consider the roles that the surgical resection of stomach and shortening of the
      bowel may also bring about this syndrome. The earlier onset is more likely due to
      surgical loss of defenses of the stomach and the later onset to a metabolic
      alteration of the presurgical obesity, involving fat metabolism, and/or the
      microbiome. The role of characteristic creeping fat of CD is also addressed.

PMID- 28489648
TI  - Clinical Experience With IV Angiotensin II Administration: A Systematic Review of
      Safety.
AB  - OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine
      activities. This is a systematic review of the safety of IV angiotensin II. DATA
      SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which
      human subjects received IV angiotensin II were selected whether or not safety was
      discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two
      reviewers and one arbiter. One thousand one hundred twenty-four studies, in which
      31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected.
      Data recorded included number of subjects, comorbidities, angiotensin II dose and
      duration, pressor effects, other physiologic and side effects, and adverse
      events. DATA SYNTHESIS: The most common nonpressor effects included changes in
      plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse
      events were infrequent and included headache, chest pressure, and orthostatic
      symptoms. The most serious side effects were exacerbation of left ventricular
      failure in patients with congestive heart failure and bronchoconstriction. One
      patient with congestive heart failure died from refractory left ventricular
      failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated
      with angiotensin II in case studies, cohort studies, and one placebo-controlled
      study. One healthy subject died after a pressor dose of angiotensin II was
      infused continuously for 6 days. No other serious adverse events attributable to
      angiotensin II were reported. Heterogeneity in study design prevented meta
      analysis. CONCLUSION: Adverse events associated with angiotensin II were
      infrequent; however, exacerbation of asthma and congestive heart failure and one
      fatal cerebral hemorrhage were reported. This systematic review supports the
      notion that angiotensin II has an acceptable safety profile for use in humans.

PMID- 28489650
TI  - Burn Care and Reconstructive Surgery.

PMID- 28489649
TI  - A Novel Computerized Test for Detecting and Monitoring Visual Attentional
      Deficits and Delirium in the ICU.
AB  - OBJECTIVES: Delirium in the ICU is associated with poor outcomes but is under
      detected. Here we evaluated performance of a novel, graded test for objectively
      detecting inattention in delirium, implemented on a custom-built computerized
      device (Edinburgh Delirium Test Box-ICU). DESIGN: A pilot study was conducted,
      followed by a prospective case-control study. SETTING: Royal Infirmary of
      Edinburgh General ICU. PATIENTS: A pilot study was conducted in an opportunistic
      sample of 20 patients. This was followed by a validation study in 30 selected
      patients with and without delirium (median age, 63 yr; range, 23-84) who were
      assessed with the Edinburgh Delirium Test Box-ICU on up to 5 separate days.
      Presence of delirium was assessed using the Confusion Assessment Method for the
      ICU. MEASUREMENTS AND MAIN RESULTS: The Edinburgh Delirium Test Box-ICU involves
      a behavioral assessment and a computerized test of attention, requiring patients
      to count slowly presented lights. Thirty patients were assessed a total of 79
      times (n = 31, 23, 15, 8, and 2 for subsequent assessments; 38% delirious).
      Edinburgh Delirium Test Box-ICU scores (range, 0-11) were lower for patients with
      delirium than those without at the first (median, 0 vs 9.5), second (median, 3.5
      vs 9), and third (median, 0 vs 10.5) assessments (all p < 0.001). An Edinburgh
      Delirium Test Box-ICU score less than or equal to 5 was 100% sensitive and 92%
      specific to delirium across assessments. Longitudinally, participants' Edinburgh
      Delirium Test Box-ICU performance was associated with delirium status.
      CONCLUSIONS: These findings suggest that the Edinburgh Delirium Test Box-ICU has
      diagnostic utility in detecting ICU delirium in patients with Richmond Agitation
      and Sedation Scale Score greater than -3. The Edinburgh Delirium Test Box-ICU has
      potential additional value in longitudinally tracking attentional deficits
      because it provides a range of scores and is sensitive to change.

PMID- 28489651
TI  - The Impact of Cervical Musculoskeletal Disorders on UK Consultant Plastic
      Surgeons: Can We Reduce Morbidity With Applied Ergonomics?
AB  - BACKGROUND: Based on anecdotal and observational evidence, we hypothesized that
      the prevalence of cervical musculoskeletal disorder (C-MSD) would be high among
      plastic surgeons. A questionnaire review was undertaken to test this hypothesis.
      Ergonomic assessment was undertaken to assess causal factors of C-MSD. METHOD: An
      anonymous questionnaire recording demographics, physical symptoms and behavioral
      responses to C-MSD was distributed to UK Plastic Surgery consultants. The
      postural impact of wearing loupes was assessed using motion capture techniques
      and recording cervical muscular activity. RESULTS: The questionnaire response
      rate was 81%. The prevalence of cervical spine morbidity was recorded as 32%.
      Employment implications included 28% of the cohort requiring sick leave. The
      professional impact was 7% permanently modifying their practice. There were 2
      factors significant for C-MSD, the surgeons' age and the duration in hours of
      wearing loupes per week. Ergonomic assessment of surgeons operating in loupes
      demonstrated: 1. increased forward and lateral cervical flexion; 2. increased
      cervical muscular activity to maintain the protracted "head forward" posture; and
      3. prolonged static posturing to maintain head position for visual focus. Table
      height adjustment and variation of loupe working distance can reduce neck
      flexion. CONCLUSIONS: Cervical morbidity is a prevalent problem among plastic
      surgeons. Long procedures, static postures and neck flexion result in the "head
      forward" posture. This posture exaggerates when operating with loupe
      magnification. Early-middle-aged consultants are more prone to cervical morbidity
      hence afflicted when at the top of their game. The work force is diminished for a
      potentially avoidable morbidity. Rather than accept this morbidity, co-operation
      between plastic surgeons and ergonomist may help to reduce injury.

PMID- 28489652
TI  - Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While
      Preserving the Wound-Healing Function of Adipose-Derived Stem Cells.
AB  - INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer
      resections; however, it may negatively affect the wound-healing potential of
      human adipose-derived stem cells (hASCs) for fat grafting and reconstructive
      surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation
      of gene expression and stabilize microtubules similarly to paclitaxel, thus,
      creating a synergistic mechanism of cell cycle arrest. We aim to combine these
      drugs to enhance cytotoxicity towards breast cancer cells, while preserving the
      wound-healing function of hASCs for downstream reconstructive applications.
      METHODS: Triple negative breast cancer cells (MBA-MB-231) and hASCs
      (institutional review board-approved clinical isolates) were treated with a
      standard therapeutic dose of paclitaxel (1.0 MUM) or with low-dose paclitaxel
      (0.1 MUM) combined with the HDACi suberoylanilide hydroxamic acid or trichostatin
      A. Cell viability, gene expression, apoptosis, and wound-healing/migration were
      measured via methylthiazol tetrazolium assay, quantitative real-time polymerase
      chain reaction, annexin V assay, and fibroblast scratch assay, respectively.
      RESULTS: Combined HDACi and low-dose paclitaxel therapy maintained cytotoxicity
      towards breast cancer cells and preserved adipose-derived stem cell viability.
      Histone deacetylase inhibitor demonstrated selective anti-inflammatory effects on
      adipose-derived stem cell gene expression and decreased expression of the
      proapoptotic gene FAS. Furthermore, HDACi therapy did not increase relative
      apoptosis within hASCs. A scratch assay demonstrated enhanced wound healing among
      injured fibroblasts indirectly co-cultured with HDACi-treated hASCs. CONCLUSIONS:
      Combining HDACi with low-dose paclitaxel improved cytotoxicity towards breast
      cancer cells and preserved hASC viability. Furthermore, enhanced wound healing
      was observed by improved migration in a fibroblast scratch assay. These results
      suggest that the addition of HDACi to taxane chemotherapy regimens may improve
      oncologic results and wound-healing outcomes after reconstructive surgery.

PMID- 28489656
TI  - Consequences of Traumatic Brain Injury in Professional American Football Players:
      A Systematic Review of the Literature.
AB  - OBJECTIVE: The purpose of this study was to systematically review the literature
      for the consequences Traumatic brain injury (TBI) has on cognitive,
      psychological, physical, and sports-related functioning in professional American
      Football players. DATA SOURCES: We performed a systematic search in 2 databases,
      PubMed and SPORTDiscus, to obtain literature from January 1990 to January 2015.
      To be eligible for inclusion, a study had to examine the relationship between TBI
      and the consequences for several aspects of functioning in professional American
      football players older than 18 years. Methodological quality was assessed using a
      5-item checklist which assessed selection bias, information bias, and correct
      reporting of the population and exposure characteristics. MAIN RESULTS: The
      search yielded 21 studies that met our inclusion criteria. An evidence synthesis
      was performed on the extracted data and resulted in 5 levels of evidence. The
      evidence synthesis revealed that there is strong evidence that concussions are
      associated with late-life depression and short-term physical dysfunctions.
      Evidence for the relationship between concussion and impaired sports-related
      function, prolonged reaction time, memory impairment, and visual-motor speed was
      inconclusive. Moderate evidence was found for the association between TBI and
      mild cognitive impairment (MCI), and limited evidence was found for the
      association between TBI and executive dysfunction. CONCLUSIONS: There is strong
      evidence that a history of concussion in American football players is associated
      with depression later in life and short-term physical dysfunctions. Also
      cognitive dysfunctions such as MCI are seen in older players with a history of
      TBI. These results provide input for actions to prevent TBI and their
      consequences in (retired) American football players.

PMID- 28489657
TI  - The Pattern of Orbital Fractures Managed at Two Referral Centers in Nairobi,
      Kenya.
AB  - Orbital fractures are one of the commonest injuries in mid-face trauma and can
      lead to significant functional and cosmetic defects. This study was aimed at
      analyzing the pattern of orbital fractures at 2 referral centers in Nairobi. It
      was a descriptive prospective hospital-based study of the demographics, etiology,
      clinico-radiological features, and management modalities among patients
      presenting with orbital fractures at the University of Nairobi Dental Hospital
      and Kenyatta National Referral Hospital in Nairobi, Kenya. A total of 60 patients
      (52 males, 8 females; P <0.05) with confirmed orbital fractures were recruited
      during the 6-months study period. Orbital fractures occurred most frequently in
      the 21 to 40-year-old age group (80%, P<0.05). The principal etiological factors
      were motor cycle crashes; 30%, interpersonal violence 23.3%, public vehicle
      crushes 20%, private vehicle crushes; 10%, injury from flying objects 10% and
      falls 8.3%. The most commonly affected anatomical sites were the floor (75%), the
      lateral wall (71.7%), infra-orbital rim (66.7%), zygomatico-frontal suture
      (63.3%). There were 5 (8.3%) cases of total blindnessThe impure orbital fractures
      that involve the satellite bones especially the zygomatic complex predominate.

PMID- 28489658
TI  - Safe and Effective Method to Transfer Pedicle Vessels in Free Flap
      Reconstruction.
AB  - Free tissue transfer is a useful method to cover soft tissue defects following
      trauma or tumor excision. At the time of transfer of the pedicle, its status is
      not investigated. Therefore, kinking of the pedicle can occur, and pedicle
      injuries can result from surgical instruments. The authors would like to
      introduce a simple, safe, and effective method to overcome these problems using a
      Penrose drain. The present method can help reconstructive microsurgeons with the
      transfer of pedicle vessels through a tunnel without torsion or injury.

PMID- 28489659
TI  - Relationship Between the Quantity of Nerve Exposure During Bilateral Sagittal
      Split Osteotomy Surgery and Sensitive Recovery.
AB  - AIM AND OBJECTIVES: The purpose of this study was to evaluate how different
      exposures of the V3 nerves during orthognathic surgery impact neurosensory
      disturbances. METHODS: The study included 127 patients who underwent either
      bilateral sagittal split osteotomy (BSSO) or BSSO with maxillary le Fort 1. They
      were divided into 6 groups, identified by the quantity of V3 nerve exposure. All
      patients were examined in a pre-op period and again after 1, 3, 6 months post-op.
      The standardized tests used were to clarify the objective and subjective
      neurosensory status of the exposed nerve. Neurosensory evaluation included; a pin
      prick test, the 2 points discriminator, light touch, warm and cold tests, and
      blunt discrimination. They were all done bilaterally on the lower lip area.
      RESULTS: In only 2 patients the nerve was damaged during surgery and thus they
      were not included in this study. In 10.2% of patients there was no nerve
      exposure, 25.2% had longitudinal vestibular segment nerve exposed, 22.8% had the
      longitudinal upper-vestibular segment exposed, 20.5% had the longitudinal lower
      vestibular segment exposed, 14.2% had the longitudinal upper-lower-vestibular
      segment exposed, and in 7.1% of patients the nerve was totally exposed. Given the
      estimated time of 1 month there was 100% recovery in patients whose nerve was
      unexposed. Considering the other patients, the authors had a variable number of
      patients who did not recover completely. CONCLUSION: The authors estimate a
      correlation between the recovery time and the quantity of the exposed nerve.
      There is a high incidence of neurosensory disturbance in the lower lip and chin
      after BSSO and intraoperative quantity of nerve exposure.

PMID- 28489660
TI  - Effects of Growth Factors From Platelet-Rich Fibrin on the Bone Regeneration.
AB  - Platelet-rich fibrin (PRF) has simple manufacturing process without risk of
      immunologic rejection or infection by additional materials. This study was
      designed to investigate the effects of platelet-derived growth factors and
      transforming growth factors-beta in PRF on the proliferation and differentiation
      of osteoblasts. The authors analyzed platelet-derived growth factors and
      transforming growth factors-beta in normal human serum (NHS) and PRF by enzyme
      linked immunosorbent assay quantitatively and those in PRF group were
      significantly increased when compared with NHS. After harvesting osteoblasts from
      iliac bone, the authors added 10% fetal bovine serum, 10% NHS, and 3% PRF to
      osteoblasts, respectively and incubated for 24, 48, 72 hours. For analysis of
      osteoblast proliferation and differentiation, the authors measured DNA synthesis
      by [3H]-thymidine isotope activity, protein synthesis by sulforhoamine B assay
      and those were increased according to elapsed time in all groups, but they were
      significantly increased in 3% PRF. The authors measured alkaline phosphatase
      activity of osteoblasts, it was increased according to elapsed to time in all
      groups, but significantly increased in 72 hours. In conclusion, application of
      PRF to bone defect sites may have an enhanced effect of bone regeneration with
      low risk of complications, and relatively simple manufacturing process.

PMID- 28489661
TI  - Use of Buccinator Myomucosal Flap in Tongue Reconstruction.
AB  - The myomucosal buccinator flap, first described by Bozola in 1989, has become an
      important tool for intraoral defects reconstruction. In the literature, there is
      a variety of proposed myomucosal cheek flaps, both pedicled and island, based on
      the buccal or the facial arteries. From January 2007 to December 2011, the
      authors used a pedicled buccinator flap based posteriorly on the buccal artery to
      reconstruct partial lingual defects following tumor resection in 27 patients. The
      buccal fat pad was translated to cover the donor site defect. After 3 to 4 weeks
      from the original surgery, a second procedure under local anesthesia was
      performed to detach the pedicle and remodel the flap. The morphological and
      functional outcomes of the procedures were evaluated by the surgeons and a speech
      and language therapist. All patients presented satisfactory results. The authors
      consider the use of the described technique as the gold standard in the
      reconstruction of partial tongue defects after tumor resection.

PMID- 28489662
TI  - Metastasis of a Renal Collecting Duct Adenocarcinoma to the Oral Cavity After
      Tooth Extraction.
AB  - Metastatic tumors rarely occur in the oral cavity. The most common of the oral
      metastases are lung cancers in males, and breast and genital cancers in females.
      The most common primary tumor metastasis to the oral cavity is from the lung,
      kidney, liver, prostate, and colorectal cancers. The metastatic lesions are
      similar to oral lesions such as pyogenic granuloma, giant cell lesions, gingival
      polyps, hemangioma, peripheral fibroma, and adenoid squamous cell carcinoma.
      Therefore, the diagnosis of primary tumors is challenging. To our knowledge, this
      is the first reported case to feature metastasis of a renal collecting duct
      adenocarcinoma to the oral cavity after tooth extraction.

PMID- 28489663
TI  - Use-dependent inhibition of glycine-activated chloride current in rat neurons by
      beta-amyloid peptide pretreated with hexafluoroisopropanol.
AB  - Hexafluoroisopropanol (HFIP) is a nonpolar organic solvent that is often used to
      prepare beta-amyloid peptide (Abeta) samples. In this work, we compare the
      effects of two different species derived from synthetic Abeta1-42 and prepared
      without HFIP (Abeta) or using HFIP (Abeta/HFIP) on the glycine-activated chloride
      current (IGly). The experiments were conducted on the pyramidal neurons isolated
      from CA3 region of rat hippocampus. Transmembrane currents were recorded using a
      conventional patch-clamp technique in the whole-cell configuration. The IGly was
      induced by a step application of the agonist for 600 ms through glass capillary.
      Abeta or Abeta/HFIP was coapplied with glycine. The effects of the two species of
      the peptide have similar and distinctive features. Both substances caused a
      reduction in the peak amplitude and an acceleration of desensitization of the
      IGly. At the same time, the effect of Abeta/HFIP was found to develop and recover
      more slowly and required several repeated applications for its saturation (use
      dependence). The effect of Abeta/HFIP was voltage independent and equally
      pronounced at negative and positive membrane potentials. First, our results
      confirm that HFIP pretreatment may influence the properties of Abeta. Second, new
      information on the glycine receptor ability to interact with drugs in use
      dependent mode was obtained.

PMID- 28489664
TI  - Changes in mitochondrial ultrastructure in SH-SY5Y cells during apoptosis induced
      by hemin.
AB  - Hemorrhagic stroke is associated with high morbidity and mortality. Hemin is a
      decomposition product of hemoglobin that is related to neuronal apoptosis after
      hemorrhage, although the molecular basis for this association remains unclear. To
      address this issue, the present study investigated hemin-induced changes in the
      apoptotic index and mitochondrial ultrastructure in SH-SY5Y cells. Cell viability
      was evaluated using Cell Counting Kit-8 and by terminal transferase dUTP nick-end
      labeling, western blotting, and flow cytometry. Changes in mitochondrial
      ultrastructure were examined by super-resolution three-dimensional structured
      illumination microscopy. We found that cleaved-caspase-3 expression and the
      number of apoptotic cells increased in a time-dependent manner upon hemin
      treatment, which was associated with mitochondrial fragmentation. Our data
      suggest that hemin induces apoptosis and mitochondrial fission in neuronal cells.
      Thus, therapeutic strategies that target hemin could mitigate the damage caused
      by hemorrhagic stroke.

PMID- 28489665
TI  - The Nogo receptor inhibits proliferation, migration and axonal extension by
      transcriptionally regulating WNK1 in PC12 cells.
AB  - Neuronal regeneration and axonal regrowth mechanisms in the injured mammalian
      central nervous system are largely unknown. As part of a major pathway for
      inhibiting axonal regeneration, activated neuronal glycosylphosphatidylinositol
      anchored Nogo receptor (NgR) interacts with LINGO-1 and p75NTR to form a complex
      at the cell surface. However, it was found in our previous report that
      upregulation of NgR stimulated by injury plays a key role in neuronal
      regeneration in the neonatal cortex freeze-lesion model, but its downstream
      signalling remains elusive. In the present study, the novel regulatory role of
      NgR in a serine-threonine kinase WNK1 was identified. NgR's transcriptional
      regulation of WNK1 was identified by RT-qPCR and semiquantitative western blot
      after the overexpression or knockdown of NgR, and the regulation is specific to
      WNK1, which is not the same for its family members, WNK2, WNK3 and WNK4.
      Furthermore, NgR inhibition by NEP fails to affect WNK1, which indicates that
      WNK1 functions outside of the Nogo-A/NgR pathway. By performing a proliferation,
      migration and axonal extension assay, we also identified that overexpressed NgR
      critically regulated these processes and impairment by overexpressing NgR was
      rescued with coexpression of WNK1, indicating the partial role of WNK1 in NgR
      mediated morphological regulation. Our study identifies a separation of functions
      for the NgR-regulated WNK1 in mediating proliferation, migration and axonal
      extension in PC12 cells as well as a specific regulatory role between NgR and
      WNK1 that is important for recovery from central nervous system injury.

PMID- 28489667
TI  - Increasing Levels of Positive End-expiratory Pressure Improve the Left
      Ventricular Strain.
AB  - PURPOSE: The goal of this study was to evaluate possible changes in the left
      myocardial performance of patients with cardiogenic shock (CS) during ascending
      levels of positive end-expiratory pressure (PEEP) using speckle-tracking
      echocardiography. MATERIALS AND METHODS: This was an interventional clinical
      study performed on CS patients under mechanical ventilation. These patients
      underwent echocardiography after 15 to 30 minutes of progressive increases in
      PEEP zero end-expiratory pressure (ZEEP) (PEEP 5, PEEP 10, PEEP 15 cm H2O). We
      evaluated the changes caused by these increasing levels of PEEP on the E/E' ratio
      and the parameters of left ventricular systolic and diastolic functions,
      including longitudinal strain (S) and strain rate (SR). Analyses of mean values
      were carried out using analysis of variance. RESULTS: A total of 65 CS patients
      were included. Their mean age was 68.58+/-14.61 years. Progressive increases in
      PEEP induced a significant decrease in the E/E' ratio (ZEEP=12.87+/-1.81; PEEP=5,
      8.39+/-3.61; PEEP=10, 6.34+/-1.73; and PEEP=15, 7.10+/-0.37; P<0.0001). Although
      we did not find significant changes in left ventricular ejection fraction, a
      clear increase in left ventricular S and SR occurred (ZEEP=-13, 15+/-1.27;
      PEEP=5, -16.97+/-4.01; PEEP=10, -16.89+/-0.46; PEEP=15, -15.39+/-4.21; and ZEEP=
      1.02+/-0.02; PEEP=5, -1.49+/-0.13; PEEP=10, -1.57+/-0.21; PEEP=15, -1.24+/-0.29,
      respectively; all values were significant). CONCLUSIONS: Increasing levels of
      PEEP improve the left ventricular S and SR. PEEP levels could modify the
      performance of left ventricular fibers.

PMID- 28489668
TI  - Treatment algorithm and management of retrohepatic vena cava injuries.

PMID- 28489669
TI  - Rasch validation and comparison of Slovenian, Croatian, and Italian versions of
      the Mini-BESTest in patients with subacute stroke.
AB  - We aimed to verify by Rasch analysis whether the Mini-BESTest, a balance measure,
      confirms its main psychometric properties in patients with subacute stroke
      undergoing rehabilitation in three different countries (Slovenia, Croatia, and
      Italy), and to examine the stability of item hierarchy and difficulty across the
      three national versions through a differential item functioning analysis. We
      investigated 159 patients with subacute stroke consecutively admitted to three
      rehabilitation facilities after screening for an intensive, tailored
      rehabilitation program. Balance function was tested within 36 h from admission
      and after ~25 days. As no differential item functioning was found between
      admission and discharge data or among countries, all data were pooled. Rasch
      criteria for the functioning of rating scale categories were fulfilled. In terms
      of internal construct validity, all items except item #14 (Cognitive Get Up & Go;
      infit value=1.42) showed an acceptable fit to the Rasch model. The patient
      ability-item difficulty matching was very good. Reliability indices were high.
      The Principal Component Analysis of standardized residuals confirmed the
      unidimensionality of the test. On the basis of the item calibration, raw scores
      of the Mini-BESTest were transformed into linear estimates of dynamic balance and
      six statistically detectable levels of balance ability were defined. Good
      psychometric features of the Mini-BESTest were confirmed. The three different
      national versions showed stability in item hierarchy, indicating equivalence of
      their cross-cultural adaptations. Problems with item #14 in these patients
      warrant further study.

PMID- 28489670
TI  - Retrospective Comparison of Fluticasone Propionate and Oral Viscous Budesonide in
      Children With Eosinophilic Esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is treated with dietary modification
      and/or pharmacologic management with swallowed topical steroids. Swallowed
      fluticasone propionate (FP) and oral viscous budesonide (OVB) have proven to be
      effective in resolving symptoms and reversing histologic changes in children and
      adults with EoE. There are minimal comparative studies between the 2 agents.
      OBJECTIVE: The aim of the study was to retrospectively compare endoscopic and
      histologic outcomes after FP versus OVB therapy in children with EoE in our
      center. METHODS: We performed a retrospective chart review of subjects diagnosed
      with EoE at a tertiary care center between 2010 and 2015. Inclusion criteria were
      FP or OVB therapy for >=8 weeks along with pre- and post-treatment endoscopic
      evaluation. Demographic and clinical features and endoscopic and histologic
      assessment were recorded for comparative analysis. Histologic response was
      defined as <15 eos/hpf and remission as <5 eos/hpf. RESULTS: The study included
      68 EoE patients (20 FP and 48 OVB) with a mean age of 10.6 +/- 5.2 years (range 1
      20 years); 81% were boys and 68% were Caucasian. No significant demographic or
      clinical differences were noted between the 2 study groups. Overall histologic
      response to topical steroids was seen in 44 of 68 (65%) patients. A significantly
      greater number of patients achieved histologic response with OVB (36/48, 75%)
      than with FP (8/20, 40%) (P = 0.0059). Mean pretreatment peak eos/hpf was 46 +/-
      19 in the FP group versus 45 +/- 23 in the OVB group. Mean post-treatment peak
      eos/hpf was 20 +/- 29 in the FP group versus 12 +/- 16 in the OVB group (P =
      0.002). There was also a significantly greater difference in the change of
      absolute eos/hpf from pre- to post-treatment in the OVB group (-33) versus FP
      (18) (P = 0.047). A greater number of OVB-treated patients without asthma had a
      histologic response compared to those with asthma (P = 0.031). The response to
      OVB was not affected by the delivery vehicle, namely sucralose (Splenda) versus
      Neocate Duocal. CONCLUSIONS: Our data suggest that treatment with OVB leads to
      better endoscopic and histologic outcomes than FP. Adherence to treatment and
      history of asthma are major determining factors in the response to treatments.
      Using Neocate Duocal as the OVB delivery vehicle is just as effective as
      sucralose.

PMID- 28489671
TI  - Closer Look at the Nutritional Outcomes of Patients After Primary Repair of
      Congenital Diaphragmatic Hernia.
AB  - OBJECTIVES: We hypothesize that the patients after primary repair of congenital
      diaphragmatic hernia (CDH) can have poor nutritional outcomes and plan to
      identify risk factors to further stratify these patients. METHODS: Retrospective
      cohort of patients who had primary repair of CDH between 2000 and 2014 and had
      follow-up at our institution. Z scores (weight for age and weight for length)
      were calculated using the World Health Organization and Centers for Disease
      Control and Prevention growth standards. RESULTS: For the 67 patients in the
      cohort, the median age at the time of repair was 3 days (interquartile range 2-5)
      and at the time of discharge was 20.5 days (interquartile range 16-30). Fifteen
      percent of the patients required supplemental tube feeding for inadequate oral
      intake and 69% required fortified feedings for inadequate growth at discharge (4
      patients subsequently needed gastrostomy tube placement). The median z scores at
      discharge were -1.0 (-2.1 to -0.3) and -1.2 (-2.3 to -0.5) in weight for age and
      weight for length, respectively. The risk factors for low z scores included open
      repair and longer periods of postoperative intubation or hospitalization. The z
      scores were similar at 6 months of age compared to discharge, but then
      statistically improved at 12 months of age. CONCLUSIONS: Patients with primary
      repair of CDH are at risk for poor nutritional outcomes at the time of hospital
      discharge and require follow-up to ensure adequate growth. Patients at highest
      risk are those who had an open repair and had prolonged intubation or
      hospitalization.

PMID- 28489672
TI  - Starved Guts: Morphologic and Functional Intestinal Changes in Malnutrition.
AB  - Malnutrition contributes significantly to death and illness worldwide and
      especially to the deaths of children younger than 5 years. The relation between
      intestinal changes in malnutrition and morbidity and mortality has not been well
      characterized; however, recent research indicates that the functional and
      morphologic changes of the intestine secondary to malnutrition itself contribute
      significantly to these negative clinical outcomes and may be potent targets of
      intervention. The aim of this review was to summarize current knowledge of
      experimental and clinically observed changes in the intestine from malnutrition
      preclinical models and human studies. Limited clinical studies have shown villous
      blunting, intestinal inflammation, and changes in the intestinal microbiome of
      malnourished children. In addition to these findings, experimental data using
      various animal models of malnutrition have found evidence of increased intestinal
      permeability, upregulated intestinal inflammation, and loss of goblet cells. More
      mechanistic studies are urgently needed to improve our understanding of
      malnutrition-related intestinal dysfunction and to identify potential novel
      targets for intervention.

PMID- 28489674
TI  - Differentiation Between Crohn Disease and Intestinal Tuberculosis in Children.
AB  - OBJECTIVES: The aim of the study was to evaluate clinical, endoscopic,
      radiologic, and histopathological features helpful in differentiating Crohn
      disease (CD) from intestinal tuberculosis (ITB) in children. METHODS: Patients
      diagnosed to have CD or ITB based on standard recommended criteria were enrolled.
      Children with inflammatory bowel disease unclassified or suspected ITB or CD with
      incomplete work-up or lost to follow-up were excluded. The clinical and
      laboratory (radiology, endoscopy, and histology) details of children were
      analyzed. RESULTS: Twenty cases of ITB (14 [3-17] years) and 23 of CD (11 [1-17]
      years) were enrolled. Presentation with chronic diarrhea (82% vs 40%; P = 0.006)
      and blood in stool (74% vs 10%; P = 0.001) favored CD, whereas subacute
      intestinal obstruction (20% vs 0%; P = 0.04) and ascites (30% vs 0%; P = 0.005)
      favored ITB. Presence of deep ulcers (61% vs 30%; P = 0.04), longitudinal ulcers
      (48% vs 15%; P = 0.02), involvement of multiple colonic segments (70% vs 35%; P =
      0.02), left-sided colon (87% vs 40%; P = 0.003), extraintestinal manifestations
      (21.7% vs 0%; P = 0.02), and higher platelet count (3.9 vs 2.6 * 10/mm; P = 0.02)
      favored CD. Isolated ileocecal involvement (40% vs 8.7%; P = 0.03) was a feature
      of ITB. TB bacilli were demonstrated in 40% ITB cases (colon-6, ascites-1,
      abdominal lymph node-1). On multivariate analysis, presence of blood in stool
      (odds ratio: 37.5 [confidence interval: 3.85-365.72], P = 0.002) and left-sided
      colonic involvement (odds ratio: 16.2 [confidence interval: 1.63-161.98], P =
      0.02) were independent predictors of CD. CONCLUSIONS: Microbiologic confirmation
      of tuberculosis is possible in 40% ITB cases. Presence of blood in stool and left
      sided colonic involvement are the most important features favoring CD.

PMID- 28489675
TI  - No Need for Routine Endoscopy in Children With Celiac Disease on a Gluten-free
      Diet.

PMID- 28489676
TI  - Suprapubic Catheter Change Methods: A Crossover Comparison Cohort Trial.
AB  - PURPOSE: The purpose of this study was to compare 2 methods of suprapubic
      catheter (SPC) change, instillation and observation. The instillation method
      requires instillation of saline to the bladder prior to SPC removal; the
      observation method is completed taking note of the angle and length at which the
      indwelling SPC is withdrawn and observation of urine from the newer catheter when
      inserted. DESIGN: Nonrandomized crossover trial. SUBJECTS AND SETTING: Fifty-nine
      community-dwelling adults who were long-term SPC users participated in the study.
      There were 38 males and 21 females, with a mean age of 68.5 years. Most had
      chronic, progressive, or complex comorbidity. The mean duration of SPC use was
      3.5 years. METHODS: Participants underwent 4 SPC changes using the instillation
      method, followed by 4 changes using the observation method. Data were collected
      using a 3-part survey document; it queried demographic and catheter-related
      clinical information, the number of symptomatic catheter-associated urinary tract
      infections (CAUTIs) requiring antibiotic treatment, the number of catheter
      blockages that occurred during data collection, and nurses' experiences during
      catheter changes (including narrative feedback-related problems, concerns, or
      comments in relation to each catheter change). The comparative CAUTI and blockage
      outcomes were analyzed using McNemar's test for 2 paired samples. Narrative data
      were analyzed using thematic analysis. RESULTS: There were 231 SPC changes using
      the observation method. No episodes of catheter displacement occurred. Analysis
      of nurses' narrative revealed concerns regarding "slowness" of urine drainage
      from the newly inserted catheter. This concern was addressed by promotion of
      adequate hydration prior to catheter change. There were 120 paired useable
      surveys included in the CAUTI and blockage incidence comparison; no statistically
      significant differences in CAUTI occurrences were found based on catheter change
      method (11 vs 11, P = .7728). No differences in the catheter blockage episodes
      were found based on catheter change method (8 vs 6, P = .7237). CONCLUSION: The
      observation method of SPC change was as effective as the instillation method.

PMID- 28489677
TI  - Futility of imaging to stage melanoma patients with a positive sentinel lymph
      node.
AB  - The use of staging imaging in melanoma patients with a positive sentinel lymph
      node (SLN) has been reported to be of limited value. Improved accuracy resulting
      from the development of time-of-flight positron emission tomography (PET) and
      ongoing image quality improvement of computed tomography (CT) may challenge this
      statement. Our retrospective study assessed the clinical value of routine staging
      CT and PET/CT imaging in a recent cohort of asymptomatic SLN-positive patients.
      Between January 2011 and April 2014, 143 patients with a positive SLN were
      routinely staged using CT of various parts of the body or whole-body PET/CT.
      Scores were assigned for level of certainty for regional or distant metastases
      and incidental second primary malignancies. Diagnostic test performance was
      assessed, as well as the number and nature of ensuing additional diagnostic
      actions. CT was performed in 102 of 143 (71%) patients and PET/CT in 41 (29%)
      patients. The use of PET/CT increased over the study period. Metastases were
      found in two of the 143 patients (true-positive yield 1.4%). Sensitivity,
      specificity and positive predictive value were 11, 73 and 4% for CT and 17, 57
      and 6%, respectively, for PET/CT. None of the 143 patients had a change in AJCC
      stage. Two other primary malignancies were found. Twenty-one (15%) patients were
      subjected to 37 additional investigations, referrals or procedures. Routine
      staging imaging with CT or PET/CT in SLN-positive patients is not useful. The
      yield is low and the results are often false positive, leading to unnecessary
      additional tests, most of which are costly and some potentially morbid.

PMID- 28489678
TI  - Safety and efficacy of the antiganglioside GD3 antibody ecromeximab (KW2871)
      combined with high-dose interferon-alpha2b in patients with metastatic melanoma.
AB  - This study evaluated the safety and clinical benefit of ecromeximab (KW2871)
      combined with high-dose interferon-alpha2b (HDI) in patients with metastatic
      melanoma. We also carried out pharmacokinetic and immune monitoring studies of
      this combination. This was an open-label, phase 1/2 study of ecromeximab plus HDI
      in patients with measurable metastatic melanoma. Eligible patients received
      ecromeximab-HDI combination therapy: ecromeximab administered intravenously once
      every 2 weeks and HDI at a dose of 20 million units (MU)/m administered
      intravenously for 5 consecutive days per week for the first 4 weeks (induction
      phase) and then at 10 MU/m subcutaneously thrice weekly through week 14
      (maintenance phase). Patients were treated with combination therapy until disease
      progression or limiting toxicity. Three dose-escalation cohorts (5, 10, and 20
      mg/m) of ecromeximab were planned. Thirty-six evaluable patients were enrolled
      including six in each of cohorts 1 and 2, and 24 in cohort 3. Median progression
      free survival was 2.53 months [95% confidence interval (CI):1.93-3.83] and it was
      1.93 months (95% CI: 1.00-3.80) in cohort 3. The median overall survival was
      10.28 months (95% CI: 6.93-16.77) and 7.78 months (95% CI: 6.03-13.97) in cohort
      3. There was no significant difference in progression-free survival or overall
      survival by BRAF mutation status. The response rate was 5.6% (95% CI: 0.68-18.7),
      with two patients showing an objective response (one complete response and one
      partial response), and the clinical benefit rate was 78% (95% CI: 61-90). Stable
      disease as best response was observed in 26 (72%) patients including five in each
      of cohorts 1 and 2, and 16 in cohort 3. Treatment-emergent adverse events
      considered related to ecromeximab treatment occurred in four (66.7%) patients in
      cohort 1, five (83.3%) patients in cohort 2, and seven (29.2%) patients in cohort
      3. Among TEAEs with a maximum severity of grade 3 or 4, those that occurred only
      in cohort 3 were related to pain, electrolyte imbalance, blood cell decreases,
      and allergic reaction. Safety and efficacies considered related to ecromeximab
      occurred in cohort 3 and included grade 3 hypersensitivity [one (4.2%)] and grade
      2 hypotension [one (4.2%)]. Regimen-limiting toxicities occurred in two (8.3%)
      patients in cohort 3: hypersensitivity (with hypertension, supraventricular
      tachycardia, bronchospasm, chills, and dyspnea) and hypotension. One patient out
      of 31 examined showed a low-level transient positivity for human antichimeric
      antibodies against ecromeximab. Pharmacokinetic measurements by enzyme-linked
      immunosorbent assay determined that administration of HDI does not influence
      serum levels of ecromeximab at 5, 10, and 20 mg/m dose levels. Ecromeximab in
      combination with HDI was generally well tolerated in patients with metastatic
      melanoma and has shown low immunogenicity. However, the clinical activity was
      limited, suggesting that future development of this combination should be
      deprioritized and that other combinations, such as with immune checkpoint
      inhibitors, should be considered.

PMID- 28489679
TI  - Ipilimumab-associated cholestatic hepatitis: a case report and literature review.
AB  - Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the
      cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes.
      It is frequently used for the treatment of unresectable or metastatic melanoma.
      Ipilimumab may lead to several immune-related disease including colitis,
      thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited
      number of cases with hepatic damage as an ipilimumab-related adverse event has
      been reported in the literature. This agent has been implicated in causing acute
      hepatitis-like liver injury. Here, we presented a case in which cholestatic
      hepatitis developed during ipilimumab use for the treatment of metastatic
      melanoma.

PMID- 28489680
TI  - Cyclic AMP-Epac signaling pathway contributes to repression of PUMA transcription
      in melanoma cells.
AB  - The universal second messenger cAMP regulates numerous cellular processes.
      Although the cAMP-signaling pathway leads to induction of gene transcription, it
      remains unknown whether this pathway contributes toward suppression of
      transcription. Here, we show that blockade of cAMP signaling using MDL12330A led
      to an increase in PUMA transcript levels, but not p21 in melanoma cells. cAMP
      downstream component Epac activation was essential for suppression of PUMA
      transcription as an Epac agonist reversed the effects of MDL12330A. These results
      suggest that transcriptional repression is one of the functions of the cAMP-Epac
      signaling pathway.

PMID- 28489681
TI  - Temporal Stress in the Operating Room: Brain Engagement Promotes "Coping" and
      Disengagement Prompts "Choking".
AB  - OBJECTIVE: To investigate the impact of time pressure (TP) on prefrontal
      activation and technical performance in surgical residents during a laparoscopic
      suturing task. BACKGROUND: Neural mechanisms enabling surgeons to maintain
      performance and cope with operative stressors are unclear. The prefrontal cortex
      (PFC) is implicated due to its role in attention, concentration, and performance
      monitoring. METHODS: A total of 33 residents [Postgraduate Year (PGY)1-2 = 15,
      PGY3-4 = 8, and PGY5 = 10] performed a laparoscopic suturing task under "self
      paced" (SP) and "TP" conditions (TP = maximum 2 minutes per knot). Subjective
      workload was quantified using the Surgical Task Load Index. PFC activation was
      inferred using optical neuroimaging. Technical skill was assessed using
      progression scores (au), error scores (mm), leak volumes (mL), and knot tensile
      strengths (N). RESULTS: TP led to greater perceived workload amongst all
      residents (mean Surgical Task Load Index score +/- SD: PGY1-2: SP = 160.3 +/-
      24.8 vs TP = 202.1 +/- 45.4, P < 0.001; PGY3-4: SP = 123.0 +/- 52.0 vs TP = 172.5
      +/- 43.1, P < 0.01; PGY5: SP = 105.8 +/- 55.3 vs TP = 159.1 +/- 63.1, P < 0.05).
      Amongst PGY1-2 and PGY3-4, deterioration in task progression, error scores and
      knot tensile strength (P < 0.05), and diminished PFC activation was observed
      under TP. In PGY5, TP resulted in inferior task progression and error scores (P <
      0.05), but preservation of knot tensile strength. Furthermore, PGY5 exhibited
      less attenuation of PFC activation under TP, and greater activation than either
      PGY1-2 or PGY3-4 under both experimental conditions (P < 0.05). CONCLUSIONS:
      Senior residents cope better with temporal demands and exhibit greater technical
      performance stability under pressure, possibly due to sustained PFC activation
      and greater task engagement. Future work should seek to develop training
      strategies that recruit prefrontal resources, enhance task engagement, and
      improve performance under pressure.

PMID- 28489682
TI  - Personalised Prehabilitation in High-risk Patients Undergoing Elective Major
      Abdominal Surgery: A Randomized Blinded Controlled Trial.
AB  - OBJECTIVE: The aim of this study was to assess the impact of personalized
      prehabilitation on postoperative complications in high-risk patients undergoing
      elective major abdominal surgery. SUMMARY BACKGROUND DATA: Prehabilitation,
      including endurance exercise training and promotion of physical activity, in
      patients undergoing major abdominal surgery has been postulated as an effective
      preventive intervention to reduce postoperative complications. However, the
      existing studies provide controversial results and show a clear bias toward low
      risk patients. METHODS: This was a randomized blinded controlled trial. Eligible
      candidates accepting to participate were blindly randomized (1:1 ratio) to
      control (standard care) or intervention (standard care + prehabilitation) groups.
      Inclusion criteria were: i) age >70 years; and/or, ii) American Society of
      Anesthesiologists score III/IV. Prehabilitation covered 3 actions: i)
      motivational interview; ii) high-intensity endurance training; and promotion of
      physical activity. The main study outcome was the proportion of patients
      suffering postoperative complications. Secondary outcomes included the endurance
      time (ET) during cycle-ergometer exercise. RESULTS: We randomized 71 patients to
      the control arm and 73 to intervention. After excluding 19 patients because of
      changes in the surgical plan, 63 controls and 62 intervention patients were
      included in the intention-to-treat analysis. The intervention group enhanced
      aerobic capacity [DeltaET 135 (218) %; P < 0.001), reduced the number of patients
      with postoperative complications by 51% (relative risk 0.5; 95% confidence
      interval, 0.3-0.8; P = 0.001) and the rate of complications [1.4 (1.6) and 0.5
      (1.0) (P =  0.001)] as compared with controls. CONCLUSION: Prehabilitation
      enhanced postoperative clinical outcomes in high-risk candidates for elective
      major abdominal surgery, which can be explained by the increased aerobic
      capacity.

PMID- 28489683
TI  - Intraoperative Use of Vasopressors Does Not Increase the Risk of Free Flap
      Compromise and Failure in Cancer Patients.
AB  - OBJECTIVE: To examine the effects of vasopressors on free flap outcomes.
      BACKGROUND: Most micro-surgeons avoid the use of vasopressors during free flap
      surgery due to concerns of vasoconstriction, which could potentially lead to
      vascular thrombosis and flap failure. Previous studies lack the statistical power
      to draw meaningful conclusions. METHODS: All free flaps between 2004 and 2014
      from a single institution were reviewed retrospectively. Vasopressors were given
      intraoperatively as an intravenous bolus when blood pressure dropped >20% from
      baseline. The timing of intraoperative vasopressor administration was divided
      into 3 phases: from anesthesia induction to 30 minutes before the start of flap
      ischemia (P1); end of P1 to 30 minutes after revascularization (P2); end of P2 to
      end of surgery (P3). Agents included phenylephrine, ephedrine and calcium
      chloride. RESULTS: A total of 5671 free flap cases in 4888 patients undergoing
      head and neck, breast, trunk, or extremity reconstruction were identified.
      Vasopressors were used intraoperatively in 85% of cases. The overall incidence of
      pedicle compromise was 3.6%, with a flap loss rate of 1.7%. A propensity score
      matching analysis showed that intraoperative use of any agents at any time of
      surgery was not associated with increased overall pedicle compromise [51/1584
      (3.2%) vs 37/792 (4.7%); P = 0.074] or flap failure rates [26/1584 (1.6%) vs
      19/792 (2.4%); P = 0.209]. Rather, there was less risk of venous congestion
      [33/1584 (2.1%) vs 31/792 (3.9%); P = 0.010]. CONCLUSIONS: Intraoperative use of
      phenylephrine, ephedrine, or calcium chloride as an intravenous bolus does not
      increase flap compromise and failure rates in cancer patients.

PMID- 28489685
TI  - Solid Organ Laceration in an Adolescent Soccer Player: A Case Report.
AB  - : Pediatric solid organ lacerations are a relatively uncommon but potentially
      dangerous injury that must be addressed urgently once recognized. Seen most often
      during recreational or team sports, they usually occur after a blunt or
      deceleration mechanism to the abdomen or flank. Depending on the severity of
      injury, solid organ laceration may not be immediately apparent clinically. This
      emphasizes the importance of sideline witnessing and evaluation, acting quickly
      once symptoms develop, and placing importance on safe sporting technique. In
      addition, management has changed over time to favor medical management for minor
      injuries, with laparotomy reserved for high-grade or hemodynamically unstable
      lacerations. Awareness of solid organ laceration in pediatric populations is more
      important than ever as they are beginning to appear in younger adolescents. Here
      we present a case of a 14-yr-old girl sustaining a grade IV liver laceration
      while playing contact team sports.

PMID- 28489684
TI  - Calculated versus Measured MVV-Surrogate Marker of Ventilatory Capacity in
      Pediatric CPET.
AB  - INTRODUCTION: Maximum voluntary ventilation (MVV), a surrogate marker of maximum
      ventilatory capacity, allows for measuring ventilatory reserve during
      cardiopulmonary exercise testing (CPET), which is necessary to assess ventilatory
      limitation. MVV can be measured directly during a patient maneuver or indirectly
      by calculating from forced expiratory volume in 1 s (FEV1 * 40). We investigated
      for a potential difference between calculated MVV and measured MVV in pediatric
      subjects, and which better represents maximum ventilatory capacity during CPET.
      METHODS: Data were collected retrospectively from CPET conducted in pediatric
      subjects for exercise-induced dyspnea from January 2014 to June 2015 at Akron
      Children's Hospital. Subjects with neuromuscular weakness, morbid obesity, and
      suboptimal effort during the testing were excluded from the study. RESULTS:
      Thirty-five subjects (mean +/- SD, age = 13.8 +/- 2.7 yr, range = 7-18 yr)
      fulfilled the criteria. Measured MVV was significantly lower than calculated MVV
      (89.9 +/- 26.4 vs 122.4 +/- 34.5 L.min; P < 0.01). The ventilatory reserve based
      on measured MVV was also significantly lower than ventilatory reserve based on
      calculated MVV (12.4% +/- 19.6% vs 36.1% +/- 13.2%; P < 0.01). Calculated MVV (as
      well as ventilatory reserve based on calculated MVV) was significantly correlated
      with ventilatory parameters. By contrast, no significant correlations were found
      between measured MVV (or ventilatory reserve based on measured MVV) and
      ventilatory parameters except for peak ventilation (peak VE). CONCLUSIONS: The
      measured MVV was significantly lower than the calculated MVV in our pediatric
      subjects. The calculated MVV was a better surrogate of maximum ventilatory
      capacity as shown by significant correlation to other ventilatory parameters
      during CPET.

PMID- 28489686
TI  - Scaling the Oxygen Uptake Efficiency Slope for Body Size in Cystic Fibrosis.
AB  - PURPOSE: The aim of this study was to describe the relationship between body size
      and oxygen uptake efficiency slope (OUES) in pediatric patients with cystic
      fibrosis (CF) and healthy controls (CON), to identify appropriate scaling
      procedures to adjust the influence of body size upon OUES. METHODS: The OUES was
      derived using maximal and submaximal points from cardiopulmonary exercise testing
      in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body
      mass (BM), and body surface area (BSA) using ratio-standard (Y/X) and allometric
      (Y/X) methods. Pearson's correlation coefficients were used to determine the
      relationship between body size and OUES. RESULTS: When scaled using the ratio
      standard method, OUES had a significant positive relationship with stature (r =
      0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative
      relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric
      exponents (b) for CF and CON were stature 3.00, BM 0.86, and BSA 1.40. A
      significant negative correlation was found between OUES and stature in the CF
      group when scaled allometrically (r = -0.37, P = 0.027). Nonsignificant (P >
      0.05) correlations for the whole group were found between OUES and allometrically
      scaled BM (CF r = -0.25, CON, r = 0.15) and BSA (CF r = -0.27, CON r = 0.13).
      CONCLUSIONS: Only allometric scaling of either BM or BSA, and not ratio-standard
      scaling, successfully eliminates the influence of body size upon OUES. Therefore,
      this enables a more direct comparison of the OUES between patients with CF and
      healthy controls.

PMID- 28489687
TI  - Consistently High Level of Cardiorespiratory Fitness and Incidence of Type 2
      Diabetes.
AB  - PURPOSE: Although the benefit of high cardiorespiratory fitness (CRF) for the
      prevention of type 2 diabetes mellitus (T2DM) is widely accepted, whether
      consistently high CRF is necessary or transiently high CRF is sufficient is
      unclear. The present study was conducted to examine the hypothesis that
      consistently high level of CRF is more beneficial than transiently high CRF for
      the prevention of T2DM. METHODS: This cohort study was conducted in nondiabetic
      7158 men age 20 to 60 yr, enrolled from 1986 to 1987. The area under the curve
      with respect to ground (AUCG) for CRF measurements during an 8-yr measurement
      period (1979-1987) was calculated as an index of integrated CRF level during the
      period. The differences (DeltaAUCP) between AUCG and peak AUC (peak CRF
      measurement period) was also calculated as an index of the presence and the size
      of a "spike" in CRF. T2DM was defined by fasting blood glucose and a self
      reported diagnosis of diabetes for participants with blood tests. For
      participants without blood tests, T2DM was defined by the result of oral glucose
      test after a nonfasting urinary test and a self-reported diagnosis of diabetes.
      T2DM was determined on health checkups until 2009. RESULTS: During the follow-up
      period, 1495 men developed T2DM. After adjustment for confounders, as compared
      with the first quartile of AUCG for CRF, the hazard ratio (95% confidence
      interval) for the second, third, and fourth quartiles were 0.87 (0.76 to 1.00),
      0.80 (0.68 to 0.95), and 0.72 (0.58 to 0.89), respectively. For CRF spike, there
      was no association between DeltaAUCP in CRF and the incidence of T2DM.
      CONCLUSIONS: Consistently higher level of CRF over time was associated with lower
      risk of T2DM.

PMID- 28489688
TI  - Hybrid PET/MRI-based delineation of gross tumor volume in head and neck cancer
      and tumor parameter analysis.
AB  - OBJECTIVES: Accurate target delineation allows an increase in radiation dose to
      the target tumor while reducing damage to the surrounding normal tissue. However,
      there is currently no standard for evaluating volumes measured by different
      imaging modalities. The aim of this study is to evaluate the feasibility of
      contouring gross tumor volume (GTV) by PET/MRI in head and neck cancer, and to
      define an adaptive threshold level (aTL) for delineating the biological target
      volume (BTV). PATIENTS AND METHODS: Eighteen head and neck cancer patients
      underwent time of flight PET/MRI before chemoradiotherapy. Different GTVs of
      primary tumors and metastatic lymph nodes were manually contoured on MRI
      (GTVMRI), PET (GTVVIS), and fused PET/MRI (GTVFUS). An MRI-based GTV contour was
      substituted for the pathologic GTV. The percentile threshold boundary of the
      maximum standardized uptake value (SUVmax) for the BTV was determined when the
      volume of BTV approached that of GTVMRI. RESULTS: All GTVs were highly correlated
      (all Pearson's r>0.85, all P<0.001). Tumor diameter strongly correlated with GTVs
      (r=0.7-0.8 for all lesions and primary tumor; r=0.8-0.9 for lymph node
      metastases). aTL and SUVmax were moderately correlated for all lesions (r=-0.692,
      P<0.001) and were strongly correlated for primary tumors (r=-0.866, P<0.001).
      CONCLUSION: Delineating GTV on hybrid PET/MRIs is feasible, and aTL, the
      threshold boundary of BTV, was correlated inversely with the SUVmax.

PMID- 28489689
TI  - Half-body single photon emission computed tomography with resolution recovery for
      the evaluation of metastatic bone disease: implementation into routine clinical
      service.
AB  - OBJECTIVES: Typically, scintigraphic evaluation of metastatic bone disease uses
      planar imaging. Although single photon emission computed tomography (SPECT)
      offers increased clinical utility, the acquisition time necessary to cover the
      required scan range (at our centre, skull vertex to mid-femur) has made its use
      in place of planar imaging impracticable. Recently, reconstruction with
      resolution recovery (RR) has allowed SPECT acquisition times to be shortened
      while maintaining acceptable image quality. This study was carried out to
      establish whether half-body SPECT with RR could replace planar scintigraphy in
      routine practice. METHODS: A series of reduced acquisition time SPECT scans were
      reconstructed retrospectively and reviewed to establish optimal reconstruction
      parameters. Twenty patients referred for evaluation of bone metastases underwent
      planar imaging, followed by half-body SPECT, reconstructed using the optimized
      parameters. SPECT and planar images were reported by an experienced radiologist,
      who reviewed image quality and recorded the number of lesions observed, their
      location, clinical significance and reporter confidence. RESULTS: SPECT images of
      acceptable quality and covering the range from skull vertex to mid-femur were
      acquired in 33 min. Audit indicated that SPECT identified clinically significant
      lesions not reported from planar views and improved lesion localization and
      reporter confidence. CONCLUSION: Reduced acquisition times together with RR
      allowed half-body SPECT for the evaluation of bone metastases to be accommodated
      within our department's schedule. Audit indicated that SPECT delivered the
      expected clinical advantages. Half-body SPECT has replaced planar imaging for the
      routine evaluation of metastatic bone disease at our centre, with ~2500 studies
      carried out to date.

PMID- 28489690
TI  - Measurement uncertainty of lesion and reference mediastinum standardized uptake
      value in lung cancer.
AB  - OBJECTIVE: To assess standardized uptake value (SUV) measurement uncertainty (MU)
      of lung cancer lesions with uptake greater than mediastinum but less than or
      equal to the liver and that of the mediastinum blood pool, and to compare lesion
      SUV with mediastinum SUV by assessing MU of their ratio. PATIENTS AND METHODS:
      Dynamic PET data involving 10 frames were retrospectively analyzed in 10
      patients, yielding maximal SUV of 25 lesions (Lesion-SUVmax), 10 mediastinum SUV,
      either maximal or mean (Med-SUVmax, Med-SUVmean), 25 Rmax ratios (=Lesion
      SUVmax/Med-SUVmax), and 25 Rmean ratios (=Lesion-SUVmax/Med-SUVmean). A mean
      coefficient of variation was calculated for each parameter, leading to relative
      measurement uncertainty (MUr), respectively. RESULTS: MU of Rmax was found to
      involve both Lesion-SUVmax and Med-SUVmax MU: MUr=33.3-23.3-21.9%, respectively
      (95% confidence level). No significant difference in MUr was found between Med
      SUVmax and Med-SUVmean and between Rmax and Rmean. CONCLUSION: Comparison between
      target lesion SUV and reference mediastinum SUV must take into account SUV MU of
      both. Therefore, no MU reduction can be expected from using the
      lesion/mediastinum SUVmax ratio instead of Lesion-SUVmax. Moreover, no MU
      reduction can be expected from using the mean mediastinum SUV instead of the
      maximal one.

PMID- 28489691
TI  - Optimal injected dose ratio of a very rapid 1-day protocol of myocardial
      perfusion imaging with cadmium-zinc-telluride single-photon emission tomography:
      simulation and phantom study.
AB  - OBJECTIVE: Cadmium-zinc-telluride detectors enable shorter acquisition durations
      in myocardial perfusion imaging (MPI), but the time interval of sequential
      scanning is still unchanged in clinical practice. We designed a very rapid 1-day
      protocol of MPI using cadmium-zinc-telluride single-photon emission tomography
      and evaluated the optimal dose ratio between two scanning acquisitions by means
      of simulations and phantom experiments. METHODS: We intended to perform a 1-day
      MPI within 140 min and simulate radioactivities in the second scan under various
      injected dose ratios. To apply this, a cardiac phantom was scanned with various
      radioactivities and scans were compared with a reference scan with the ideal
      tracer concentrations. RESULTS: In the stress-first protocol, the dose ratio 1 :
      5 was enough to show the same regional percentage uptake compared with the
      reference. However, in the rest-first protocol, the regional percentage uptakes
      were higher than those of the reference image even with a 1 : 6 dose ratio.
      CONCLUSION: The injected dose ratio 1 : 5 is optimal in a stress-first rapid 1
      day protocol. The rest-first protocol is not appropriate because a dose ratio
      greater than 1 : 6 is required to withdraw shine-through artifacts.

PMID- 28489692
TI  - TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS WITH VASCULAR
      ENDOTHELIAL GROWTH FACTOR INHIBITORS IN EVERYDAY PRACTICE: Identification of
      Health Care Constraints in Germany-The PONS Study.
AB  - PURPOSE: The PONS study was conceived to analyze the extent of nonpersistence
      (NP) and nonadherence (NA) in the treatment of patients with neovascular age
      related macular degeneration in everyday clinical practice in Germany. Further
      objectives were to identify factors that can affect NP and NA and to analyze
      clinical outcomes under everyday conditions. METHODS: Nonpersistence (no contact
      with doctor for at least 3 months) and NA (no treatment or follow-up for at least
      6 weeks) as well as clinical data were analyzed up to 24 months retrospectively
      and 12 months prospectively in 480 patients with neovascular age-related macular
      degeneration in 23 treatment centers. Patients were interviewed for factors
      possibly affecting NP and NA. RESULTS: One third of patients fulfilled criteria
      of NA in the first 3 months and two thirds after 6 months. The NP was 18.8% after
      12 months. Treatment exclusively at one center, a higher number of patients with
      neovascular age-related macular degeneration at the treating center, and fixed
      appointments were associated with a lower risk for NP. An initial gain in visual
      acuity after upload was not preserved after 12 months (mean change -0.5 Early
      Treatment Diabetic Retinopathy Study letters). Whereas visual acuity declined by
      7.5 Early Treatment Diabetic Retinopathy Study letters in patients with good
      baseline visual acuity >20/40, visual acuity improved by 8.5 letters in patients
      with baseline visual acuity of <=20/200. Only 7.5% of patients underwent an
      optical coherence tomography scan after 3 upload injections, and only 2.0 optical
      coherence tomographies were performed in the first 12 months. CONCLUSION: The NP
      and NA were high in our study population and are likely to have contributed to a
      suboptimal clinical outcome compared with randomized clinical trials.
      Shortcomings in the management of patients with neovascular age-related macular
      degeneration, including restrictions in the timely and adequate follow-up
      (including optical coherence tomography) and retreatment, appear to be
      constraining factors in Germany.

PMID- 28489693
TI  - DYSFUNCTIONAL AUTONOMIC REGULATION OF THE CHOROID IN CENTRAL SEROUS
      CHORIORETINOPATHY.
AB  - PURPOSE: To study the effect of changing perfusion pressures on retinal and
      choroidal structure in central serous chorioretinopathy (CSC). METHODS: This
      prospective observational case series included seven healthy volunteers (14 eyes)
      and seven patients (14 eyes) with CSC. Each patient underwent spectral domain
      optical coherence tomography with enhanced depth imaging in the upright (sitting)
      and supine positions. Image segmentation focused on central macular thickness,
      subretinal fluid, total macular volume, choroidal thickness, and choriocapillaris
      thickness. Blood pressure and heart rate were measured in the upright and supine
      positions. RESULTS: Choriocapillaris thickness was thicker in CSC participants
      (34.23 MUm; range, 30.9-36.5 MUm) compared with healthy controls (13.96 MUm;
      range, 7.15-23.87 MUm) (P <= 0.001). The choroid was similarly thicker in CSC
      participants (371.4 MUm; range, 200.2-459.4 MUm) compared with healthy controls
      (231.4 MUm; range 161.8-287.5 MUm) (P <= 0.001). Choroidal thickness increased in
      patients with CSC when transitioning from upright (371.4 MUm) to supine (377.8
      MUm) (P <= 0.01). By contrast, there was an 11.97% decrease in choroid thickness
      in normal controls when transitioning from upright (231.4 MUm) to supine (203.9
      MUm). There were no significant hemodynamic changes. CONCLUSION: We demonstrated
      that choroidal thickness increased in response to increased perfusion pressures
      in patients with CSC and not in normal controls. These findings likely represent
      an autonomic dysregulation of choroidal blood flow in patients with CSC.

PMID- 28489694
TI  - EFFICACY OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN THE TREATMENT OF VITREOUS
      HEMORRHAGE RELATED TO PROLIFERATIVE DIABETIC RETINOPATHY.
AB  - PURPOSE: To investigate the efficacy of intravitreal ranibizumab injections in
      proliferative diabetic retinopathy associated with vitreous hemorrhage (VH).
      METHODS: A prospective study including patients with proliferative diabetic
      retinopathy who presented with persistent VH. Vitreous hemorrhage was graded into
      mild, moderate, and severe. Patients were randomized into two groups: the
      ranibizumab group was treated with intravitreal injections of ranibizumab and the
      control group was assigned to observation alone. Vitrectomy was performed if
      there was any aggravation of the VH in patients with mild, moderate, and severe
      VH or in the absence of improvement by 16 weeks in patients with moderate and
      severe VH. RESULTS: The ranibizumab group included 71 patients and the control
      group included 62 patients. There was a statistically significant difference in
      the vitrectomy rate in patients with mild-to-moderate VH (5 patients [7.04%] and
      12 patients [19.35%], respectively; P = 0.04). However, there was no
      statistically significant difference in the overall vitrectomy rate, and in the
      vitrectomy rate in severe VH (17 [23.94%] and 12 [16.90%] patients in the
      ranibizumab group vs. 22 [35.48%] and 10 [16.13%] patients in the control group,
      P = 0.14 and P = 0.83, respectively). Recurrence of the VH occurred in 22
      patients in the ranibizumab group and 29 patients in the control group (P =
      0.06). Better visual acuity measurements were recorded on all follow-up visits in
      the ranibizumab group (P <= 0.04). CONCLUSION: Intravitreal ranibizumab
      injections could be considered in proliferative diabetic retinopathy patients
      with mild and moderate VH.

PMID- 28489695
TI  - CLASSIFICATION OF HALLER VESSEL ARRANGEMENTS IN ACUTE AND CHRONIC CENTRAL SEROUS
      CHORIORETINOPATHY IMAGED WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To compare the prevailing patterns of Haller vessel arrangements at the
      posterior pole between healthy eyes and those with central serous
      chorioretinopathy (CSC) using en face optical coherence tomography. METHODS: Eyes
      of normal subjects and patients with acute or chronic CSC underwent optical
      coherence tomography imaging (RTVue 100; Optovue Inc, Fremont, CA). En face
      sections at the level of the Haller layer were classified by two masked graders
      into five mutually exclusive morphologic categories (temporal herringbone,
      branched from below, laterally diagonal, double arcuate, and reticular). The
      relative prevalence of each Haller vessel arrangement pattern was determined for
      each phenotype. RESULTS: Numbers of eyes examined were as follows: 154 eyes of 77
      normal subjects; 41 eyes of 31 patients with acute CSC; and 39 eyes of 33
      patients with chronic CSC. The mean age of participants was 44.4 +/- 14.6 years
      for healthy subjects (M:F = 37:40), 48.5 +/- 8.2 years (M:F = 24:7) for acute
      CSC, and 65.3 +/- 13.1 years (M:F = 28:5) for chronic CSC. The relative
      prevalence of each Haller vessel arrangement pattern differed by phenotype. The
      temporal herringbone pattern was most prevalent in healthy eyes (49.2%), whereas
      a reticular pattern was most prevalent in eyes with acute and/or chronic CSC
      (combined, 48.8%). CONCLUSION: A significant difference was observed in the
      prevalence of respective Haller vessel arrangement patterns between eyes of
      normal subjects and those of patients with either acute or chronic CSC. Although
      further study is needed to determine the mechanistic factors underlying these
      differences, and the hemodynamic implications, our data suggest that en face
      optical coherence tomography may find a formal role in choroidal disease
      classification.

PMID- 28489696
TI  - PREDICTORS OF REFRACTORY MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION
      FOLLOWING INTRAVITREAL BEVACIZUMAB.
AB  - PURPOSE: To evaluate the predictors of refractory macular edema (ME) that
      develops despite multiple bevacizumab injections in patients with branch retinal
      vein occlusion (BRVO). METHODS: A total of 107 patients who followed at least 2
      years were assigned to 2 groups: a refractory group (n = 56) and a responsive
      group (n = 51). Baseline characteristics, treatment response at 3 months, and
      fluorescein angiographic findings at 6 months were compared. Then we tried to
      identify factors associated with refractory ME development. RESULTS: Compared to
      the responsive group, the refractory group had older age, longer pre-treatment
      duration, and shorter occlusion distance from disk. At 3 months, the refractory
      group exhibited lower visual acuity, thicker central retinal thickness (CRT), and
      larger proportion of external limiting membrane (ELM) and outer plexiform layer
      disruption. After 6 months, proportion of unresolved vein occlusion, macular
      ischemia, number of microaneurysms, and non-perfusion areas were higher in the
      refractory group. Refractory ME was associated with pre-treatment duration >=3
      months, short occlusion distance from disk, thick CRT and ELM disruption at 3
      months, and unresolved vein occlusion at 6 months. CONCLUSION: If BRVO-ME
      patients exhibit the above-mentioned characteristics, they may have refractory
      ME, which should inform treatment decisions.

PMID- 28489697
TI  - Validating the Quality of Life After Brain Injury Through Rasch Analysis.
AB  - OBJECTIVE: The Quality of Life after Brain Injury (QOLIBRI), a cross-cultural
      instrument, has been validated in several languages; however, traditional
      psychometric approaches have critical limitations. Therefore, we applied the
      Rasch model for validating the 37-item QOLIBRI scale among a Chinese population
      with traumatic brain injury. PARTICIPANTS AND SETTING: In total, 587 participants
      (mean age: 44.2 +/- 15.4 years; women, 46.3%) were surveyed in neurosurgery
      departments at 6 hospitals in Taipei, Taiwan. MAIN OUTCOME MEASURE: The QOLIBRI.
      RESULTS: Of the 6 subscales of the QOLIBRI, 4 (cognition, self, daily life and
      autonomy, and social relationships) were unidimensional, valid, and reliable,
      whereas the remaining 2 (emotions and physical problems) exhibited poor
      unidimensionality, item and person reliability, and person-item targeting. Five
      items (energy, concentrating, getting out and about, sex life, and achievements)
      showed considerable differential item functioning among age groups, disability
      levels, and time since traumatic brain injury. CONCLUSION: According to item
      response theory, we identified psychometric issues in the emotions and physical
      problems subscales of the QOLIBRI as well as several differential item
      functioning items. Future research is required to determine whether similar
      results are observed in other language versions of the QOLIBRI or in other
      countries.

PMID- 28489698
TI  - Epidemiology of Isolated Versus Nonisolated Mild Traumatic Brain Injury Treated
      in Emergency Departments in the United States, 2006-2012: Sociodemographic
      Characteristics.
AB  - OBJECTIVES: To describe the frequencies and rates of mild traumatic brain injury
      (mTBI) emergency department (ED) visits, analyze the trend across the years, and
      compare sociodemographic characteristics of visits by mTBI type (ie, mTBI as the
      only injury, or present along with other injuries). DESIGN: Population-based
      descriptive study using data from the Nationwide Emergency Department Sample
      (2006-2012). METHODS: Joinpoint regression was used to calculate the average
      annual percent changes of mTBI incidence rates. Characteristics between isolated
      and nonisolated visits were compared, and the odds ratios were reported. RESULTS:
      The rate per 100 000 population of mTBI ED visits in the United States increased
      significantly from 569.4 (in 2006) to 807.9 (in 2012). The highest rates were
      observed in 0- to 4-year-olds, followed by male 15- to 24-year-olds and females
      65 years and older; the lowest rates were among 45- to 64-year-olds. The majority
      (70%) of all visits were nonisolated and occurred more frequently in residents of
      metropolitan areas. Falls were the leading external cause. Most visits were
      privately insured or covered by Medicare/Medicaid, and the injury occurred on
      weekdays in predominantly metropolitan hospitals in the South region.
      CONCLUSIONS: The burden of mTBI in US EDs is high. Most mTBI ED visits present
      with other injuries. Awareness of sociodemographic factors associated with
      nonisolated mTBI may help improve diagnosis in US EDs. This information has
      implications for resource planning and mTBI screening in EDs.

PMID- 28489699
TI  - Incidence and Associated Risk Factors of Traumatic Brain Injury in a Cohort of
      Homeless and Vulnerably Housed Adults in 3 Canadian Cities.
AB  - OBJECTIVE: To examine the factors associated with incident traumatic brain injury
      (TBI) among homeless and vulnerably housed persons over a 3-year follow-up
      period. SETTING AND PARTICIPANTS: Data were obtained from the Health and Housing
      in Transition study, which tracked the health and housing status of 1190 homeless
      or vulnerably housed individuals in 3 Canadian cities for 3 years. DESIGN AND
      MAIN MEASURES: Main measure was self-reported incident TBI during the follow-up
      period. Factors associated with TBI were ascertained using mixed-effects logistic
      regression. RESULTS: During first, second, and third years of follow-up, 187
      (19.4%), 166 (17.1%), and 172 (17.9%) participants reported a minimum of 1
      incident TBI, respectively. Among 825 participants with available data for all 3
      years of follow-up, 307 (37.2%) reported at least 1 incident TBI during the 3
      year follow-up period. Lifetime prevalence of TBI, endorsing a history of mental
      health diagnoses at baseline, problematic alcohol and drug use, younger age,
      poorer mental health, and residential instability were associated with increased
      risk of incident TBI during follow-up period. CONCLUSION: Mental health support
      and addressing residential instability and problematic substance use may reduce
      further risk of TBI and its associated poor health and social outcomes in this
      population.

PMID- 28489700
TI  - P300 Event-Related Potentials Differentiate Better Performing Individuals With
      Traumatic Brain Injury: A Preliminary Study of Semantic Processing.
AB  - OBJECTIVE: To measure the effect of traumatic brain injury on the cognitive
      processing of words, as measured by the P300, in a semantic categorization task.
      PARTICIPANTS: Eight adults with a history of moderate to severe traumatic brain
      injury and 8 age- and gender-matched controls. DESIGN: A pilot study measuring
      cognitive event-related potentials in response to word pairs that were either in
      same or different semantic categories. MAIN MEASURES: The P300 (P3b) component of
      the auditory event-related potential and neuropsychological assessment. RESULTS:
      Two patterns of P300 amplitude related to brain injury were observed.
      Participants with poorer performance on neuropsychological tests exhibited
      reduced P300 amplitude as compared to controls but showed the typical P300
      parietal scalp distribution. In contrast, better performing participants
      demonstrated robust P300 amplitude but a substantially altered scalp
      distribution, characterized by the recruitment of anterior brain regions in
      addition to parietal activation. CONCLUSIONS: The recruitment of frontal areas
      after traumatic brain injury may represent compensatory neural mechanisms
      utilized to successfully maximize task performance. The P300 in a semantic
      processing paradigm may be a sensitive marker of neural plasticity that could be
      used to improve functional outcomes in cognitive remediation paradigms.

PMID- 28489701
TI  - Pediatricians' Knowledge, Attitudes, and Behaviors to Screening Children After
      Complicated Mild TBI: A Survey.
AB  - OBJECTIVE: To understand pediatricians' attitudes, knowledge, and behaviors about
      the care of children with complicated mild traumatic brain injury (TBI).
      PARTICIPANTS: A total of 3500 pediatricians randomly selected from the American
      Medical Association Master File. DESIGN: It was a cross-sectional survey. MAIN
      MEASURES: A survey developed to assess pediatricians' attitudes toward following
      children with complicated mild TBI for cognitive and behavioral sequelae; their
      knowledge of TBI sequelae; and their usual evaluation and management of children
      after TBI. RESULTS: There were 576 (16.5%) completed responses. Most
      pediatricians (51%) see 1 or 2 patients with complicated mild TBI annually. Most
      do not think that pediatricians are the correct clinician group to be primarily
      responsible for following children with complicated mild TBI for cognitive (74%)
      or behavioral sequelae (54%). Pediatricians report difficulty referring children
      for cognitive (56%) and behavioral (48%) specialty services. Pediatricians have
      good knowledge of short-term complications of complicated mild TBI. CONCLUSION:
      Pediatricians do not think they are the clinicians that should primarily care for
      children after hospitalization for complicated mild TBI; however, other
      clinicians are frequently not accessible. Pediatricians need educational and
      referral support to provide surveillance for injury sequelae in this group of
      children.

PMID- 28489703
TI  - A Survey of Clinicians Working in Brain Injury Rehabilitation: Are Social
      Cognition Impairments on the Radar?
AB  - OBJECTIVES: To examine the social cognition assessment practices of clinicians
      working with children and adults with traumatic brain injury. MAIN MEASURES:
      Online survey addressing frequency of social cognition impairments, how these are
      assessed and obstacles to same, and treatment practices. PARTICIPANTS: A total of
      443 clinicians worldwide working in inpatient and outpatient settings. RESULTS:
      While 84% of clinicians reported that more than half of their clients with severe
      traumatic brain injury had social cognition impairments, 78% of these reported
      that they infrequently or never assessed these domains using a formal assessment
      tool. Lack of reliable tests was most frequently (33% of respondents) cited as
      the greatest barrier to undertaking social cognition assessment. CONCLUSIONS AND
      IMPLICATIONS: Improvements are needed in the development and norming of
      instruments capable of detecting social cognition impairments in the traumatic
      brain injury population. Additional training and education is needed in the use
      of social cognition assessment tools.

PMID- 28489702
TI  - The Minimal Clinically Important Difference for the Mayo-Portland Adaptability
      Inventory.
AB  - OBJECTIVES: To determine the Minimal Clinically Important Difference (MCID) and
      Robust Clinically Important Difference (RCID) of the Mayo-Portland Adaptability
      Inventory-4 (MPAI-4) as measures of response to intervention. METHODS:
      Retrospective analysis of existing data. Both distribution- and anchor-based
      methods were used to triangulate on the MCID and to identify a moderate, that is,
      more robust, level of change (RCID) for the MPAI-4. These were further evaluated
      with respect to clinical provider ratings. PARTICIPANTS: Data for individuals
      with acquired brain injury in rehabilitation programs throughout the United
      States in the OutcomeInfo Database (n = 3087) with 2 MPAI-4 ratings. MAIN
      MEASURES: MPAI-4, Supervision Rating Scale, Clinician Rating of Global Clinical
      Improvement. RESULTS: Initial analyses suggested 5 T-score points (5T) as the
      MCID and 9T as the RCID. Eighty-one percent to 87% of clinical raters considered
      a 5T change and 99% considered a 9T change to indicate meaningful improvement.
      CONCLUSIONS: 5T represents the MCID for the MPAI-4 and 9T, the RCID. Both values
      are notably less than the Reliable Change Index (RCI). While the RCI indicates
      change with a high level of statistical confidence, it may be insensitive to
      change that is considered meaningful by providers and participants as indicated
      by the MCID.

PMID- 28489704
TI  - Factors Associated With Rehabilitation Outcomes After Traumatic Brain Injury:
      Comparing Functional Outcomes Between TBIMS Centers Using Hierarchical Linear
      Modeling.
AB  - OBJECTIVE: To examine differences in patient outcomes across Traumatic Brain
      Injury Model Systems (TBIMS) rehabilitation centers and factors that influence
      these differences using hierarchical linear modeling (HLM). SETTING: Sixteen
      TBIMS centers. PARTICIPANTS: A total of 2056 individuals 16 years or older with
      moderate to severe traumatic brain injury (TBI) who received inpatient
      rehabilitation. DESIGN: Multicenter observational cohort study using HLM to
      analyze prospectively collected data. MAIN OUTCOME MEASURES: Functional
      Independence Measure and Disability Rating Scale total scores at discharge and 1
      year post-TBI. RESULTS: Duration of posttraumatic amnesia (PTA) demonstrated a
      significant inverse relationship with functional outcomes. However, the magnitude
      of this relationship (change in functional status for each additional day in PTA)
      varied among centers. Functional status at discharge from rehabilitation and at 1
      year post-TBI could be predicted using the slope and intercept of each TBIMS
      center for the duration of PTA, by comparing it against the average slope and
      intercept. CONCLUSIONS: HLM demonstrated center effect due to variability in the
      relationship between PTA and functional outcomes of patients. This variability is
      not accounted for in traditional linear regression modeling. Future studies
      examining variations in patient outcomes between centers should utilize HLM to
      measure the impact of additional factors that influence patient rehabilitation
      functional outcomes.

PMID- 28489705
TI  - RETINAL AND CHOROIDAL VASCULAR OCCLUSION FOLLOWING AQUEOUS MISDIRECTION SYNDROME
      IN A PATIENT WITH SICKLE CELL TRAIT.
AB  - PURPOSE: To report a patient with retinal and choroidal vascular occlusion as a
      presenting sign of sickle cell trait following the development of aqueous
      misdirection syndrome. METHODS: Retrospective chart review. RESULTS: A patient
      treated for bilateral chronic angle-closure glaucoma with sequential EX-PRESS
      glaucoma filtration device surgery developed sequential bilateral aqueous
      misdirection syndrome. The left eye developed retinal arterial and localized
      choroidal vascular occlusions subsequent to an acute elevation in intraocular
      pressure and possibly the use of oral acetazolamide. The patient was subsequently
      found to have sickle cell trait. The right eye developed aqueous misdirection
      with acute elevation of intraocular pressure as well, but the patient was not
      treated with oral acetazolamide and did not develop vascular occlusion.
      CONCLUSION: Retinal and choroidal vascular occlusions can be the presenting sign
      of a patient with sickle cell trait. Sickle cell screening may be beneficial in
      African American or Middle Eastern patients after an acute rise in intraocular
      pressure, particularly before initiation of treatment with oral carbonic
      anhydrase inhibitors.

PMID- 28489706
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CONGENITAL SIMPLE HAMARTOMA OF THE
      RETINAL PIGMENT EPITHELIUM.
AB  - PURPOSE: To describe the optical coherence tomography angiography features of
      congenital simple hamartoma of the retinal pigment epithelium. METHODS: Case
      report. RESULTS: A 14-year-old boy was referred for an asymptomatic fundus tumor
      in the left eye. Visual acuity was 20/20 in the right eye and 20/40 in the left
      eye. The right fundus was normal. The left fundus disclosed a gray-white nodular
      retinal mass of 2-mm diameter in the juxtafoveal region, protruding into the
      vitreous cavity and causing radial retinal folds. The mass demonstrated
      echodensity without calcification on ultrasonography, hypoautofluorescence on
      short-wavelength autofluorescence, and mixed hyporeflective and hyperreflective
      areas on near-infrared reflectance imaging. By fluorescein angiography, the mass
      showed absolute hypofluorescence through the arteriovenous phase and diffuse late
      hyperfluorescence and staining. Optical coherence tomography revealed an
      optically dense lesion with abrupt posterior shadowing, whereas optical coherence
      tomography angiography showed an extensive haphazard intratumoral vascular
      network with fairly large-caliber (100-200 microns) vessels occupying full
      thickness tumor, demonstrating more vascular details than visualized on
      fluorescein angiography. Serial segmental evaluation of the optical coherence
      tomography angiography en face images confirmed an intratumoral vascular network
      for full tumor depth down to retinal pigment epithelium, not related to
      projection artifact. Final diagnosis was congenital simple hamartoma of the
      retinal pigment epithelium. Considering the benign tumor, observation was
      recommended. CONCLUSION: Optical coherence tomography angiography of congenital
      simple hamartoma of the retinal pigment epithelium revealed an extensive
      intratumoral, haphazard, large-caliber vascular network, more evident than seen
      on fluorescein angiography. Optical coherence tomography angiography has added
      new insight into this rare tumor.

PMID- 28489707
TI  - INTRAVITREAL DEXAMETHASONE (OZURDEX) IMPLANT FOR RADIATION MACULOPATHY SECONDARY
      TO STEREOTACTIC RADIOTHERAPY FOR POSTERIOR UVEAL MELANOMA.
AB  - PURPOSE: To evaluate the efficacy of 0.7 mg intravitreal dexamethasone implant in
      the treatment of radiation maculopathy after stereotactic radiotherapy for
      posterior uveal melanoma. METHODS: Retrospective chart review of seven eyes of
      seven consecutive patients was performed. Extracted data included age, sex,
      initial and follow-up visual acuities and central macular thickness values,
      intraocular pressure, follow-up time, number of implants, and time elapsed from
      radiotherapy to implantation. Main outcome measures were visual acuity and
      central macular thickness. Glaucoma, cataract formation, or systemic side
      effects, if any, were recorded. RESULTS: Female to male ratio was 4:3. Mean age
      was 49.9 +/- 17.0 (range: 27-73). Initial mean visual acuity was 20.4 +/- 12.5
      Early Treatment Diabetic Retinopathy Study letters and initial central macular
      thickness measured 514.1 +/- 135.1 MUm on spectral domain optical coherence
      tomography. All patients except one showed improvement in visual acuity and a
      mean improvement of 7.4 +/- 6.2 letters was observed in the whole group (range: 0
      16). The mean reduction in central macular thickness was 226.7 +/- 157.0 MUm
      after a mean 9.1 +/- 3.4 months of follow-up. On average, implantation of
      intravitreal dexamethasone was performed 35.2 +/- 16.5 months after radiotherapy.
      Four patients were treatment naive and three had previous intravitreal
      bevacizumab injections with limited response. Ozurdex reimplantations were
      performed in four patients and the mean number of injections was 1.7 +/- 0.8.
      Mean time to reimplantation was 5.0 +/- 2.12 months. Only one patient developed
      posterior subcapsular cataract and all patients had intraocular pressures within
      normal limits. No systemic side effects were observed. CONCLUSION: In our
      experience, intravitreal implantation of 0.7 mg dexamethasone is an anatomically,
      and to a lesser extent functionally effective procedure for radiation maculopathy
      after stereotactic radiotherapy for posterior uveal melanoma.

PMID- 28489708
TI  - MUC1, MUC5AC, and MUC6 polymorphisms, Helicobacter pylori infection, and gastric
      cancer: a systematic review and meta-analysis.
AB  - The risk of Helicobacter pylori (HP) infection, as well as gastric cancer (GC),
      in association with genetic polymorphisms of gene encoding for mucins, has been
      investigated with contradictory results. We carried out this systematic review
      and meta-analysis to summarize the relationship between MUC1, MUC5AC, and MUC6
      polymorphisms and HP infection, as well as GC risk. We searched MEDLINE, ISI Web
      of Science, Scopus bibliographic databases and the HuGE Navigator database. Odds
      ratios (ORs) and 95% confidence interval (CI) were calculated to assess the
      association between the genetic polymorphisms, and HP/GC risk. A random-effect
      model was used to calculate the pooled ORs, overall and by ethnicity. Twenty-one
      studies were included, of which five on HP and 18 on GC, of which two were in
      common. The meta-analysis of 10 studies on the MUC1 rs4072037 polymorphism and GC
      risk reported an OR of 0.66 (95% CI: 0.57-0.78) for the dominant model (AG/GG vs.
      AA). When stratifying for ethnicity, an OR of 0.73 (95% CI: 0.62-0.86) was
      reported for the Asian population and an OR of 0.48 (95% CI: 0.38-0.61) was
      reported for the White population. Our study confirms the protective effect of
      MUC1 rs4072037 polymorphism on the risk of GC under the dominant model. Further
      studies reporting information on HP status in cases and controls would be
      required to evaluate whether the protective effect of MUC1 protein might be
      attributable to a protective effect towards the HP infection, or through
      different mechanisms.

PMID- 28489709
TI  - Your Academy: Opportunities and Challenges.

PMID- 28489710
TI  - Survival Guide for the Orthopaedic Surgery Match.
AB  - The process of matching into an orthopaedic surgery residency program can be
      daunting for medical students. Rumors, innuendo, urban myths, and electronic
      misinformation can accentuate the angst experienced by students both domestically
      and internationally. This article dispels myths and presents an up-to-date,
      evidence-based (where possible), and experience-laden road map to assist medical
      students interested in pursuing a career in orthopaedic surgery. Our framework
      takes into account the program selection, test scores, letters of recommendation,
      visiting rotations, interviews, and communication. We hope that this survival
      guide will serve as a reference point assisting medical students in achieving
      successful matches into orthopaedic surgery residency programs.

PMID- 28489711
TI  - Resident Selection Beyond the United States Medical Licensing Examination.
AB  - The resident application process has matured over the decades to become an
      efficient system. An unforeseen consequence of this efficiency is the massive
      number of applications that each orthopaedic surgery residency program must sort
      through to arrive at a manageable rank list. The most widely used filter in
      today's application cycle is an applicant's performance on the United States
      Medical Licensing Examination Step 1. Although no evidence exists to prove that
      this examination is predictive of any of the potentially defining characteristics
      of a successful resident, orthopaedic surgery programs historically have had few
      alternative options. A growing body of literature suggests that a more focused
      investigation of an applicant's inherent personality traits, as evidenced by his
      or her past accomplishments, as well as a structured use of questionnaires as
      part of the application process may improve the ability of orthopaedic surgery
      residency programs to predict who will be a successful resident.

PMID- 28489712
TI  - Maximizing Surgical Skills During Fellowship Training.
AB  - Orthopaedic surgery fellowship provides an opportunity to further develop skills
      in a particular subspecialty. However, the condensed time frame, complex skill
      acquisition, and clinical demands require efficient and effective learning
      techniques to achieve mastery. As with any advanced task, success during
      fellowship training can be achieved with active participation and a goal-directed
      approach. Skill acquisition can be successfully achieved by following a framework
      that includes preparation, execution, and reflection for every surgical case.

PMID- 28489713
TI  - Denervation of the Wrist Joint for the Management of Chronic Pain.
AB  - Wrist denervation for the management of chronic wrist pain is a safe and
      effective procedure that can delay or eliminate the need for more invasive and
      kinematically compromising salvage procedures. Wrist denervation has become
      increasingly popular since it was first described in 1959, and the technique has
      evolved from more extensive denervations to limited single-incision approaches.
      Many physicians have performed this procedure as a palliative approach to
      managing chronic wrist pain and as an adjunct to other procedures.

PMID- 28489714
TI  - Feasibility of and Rationale for the Collection of Orthopaedic Trauma Surgery
      Quality of Care Metrics.
AB  - INTRODUCTION: Reproducible metrics are needed to evaluate the delivery of
      orthopaedic trauma care, national care, norms, and outliers. The American College
      of Surgeons (ACS) is uniquely positioned to collect and evaluate the data needed
      to evaluate orthopaedic trauma care via the Committee on Trauma and the Trauma
      Quality Improvement Project. METHODS: We evaluated the first quality metrics the
      ACS has collected for orthopaedic trauma surgery to determine whether these
      metrics can be appropriately collected with accuracy and completeness. The
      metrics include the time to administration of the first dose of antibiotics for
      open fractures, the time to surgical irrigation and debridement of open tibial
      fractures, and the percentage of patients who undergo stabilization of femoral
      fractures at trauma centers nationwide. These metrics were analyzed to evaluate
      for variances in the delivery of orthopaedic care across the country. RESULTS:
      The data showed wide variances for all metrics, and many centers had incomplete
      ability to collect the orthopaedic trauma care metrics. There was a large
      variability in the results of the metrics collected among different trauma center
      levels, as well as among centers of a particular level. DISCUSSION: The ACS has
      successfully begun tracking orthopaedic trauma care performance measures, which
      will help inform reevaluation of the goals and continued work on data collection
      and improvement of patient care. Future areas of research may link these
      performance measures with patient outcomes, such as long-term tracking, to assess
      nonunion and function. This information can provide insight into center
      performance and its effect on patient outcomes. CONCLUSIONS: The ACS was able to
      successfully collect and evaluate the data for three metrics used to assess the
      quality of orthopaedic trauma care. However, additional research is needed to
      determine whether these metrics are suitable for evaluating orthopaedic trauma
      care and cutoff values for each metric.

PMID- 28489715
TI  - Assessment of Malpractice Claims Associated With Acute Compartment Syndrome.
AB  - BACKGROUND: Because acute compartment syndrome is one of the few limb-threatening
      and life-threatening orthopaedic conditions and is difficult to diagnose, it is a
      frequent source of litigation. Understanding the factors that lead to plaintiff
      verdicts and higher indemnity payments may improve patient care by identifying
      common pitfalls. METHODS: The VerdictSearch legal claims database was queried for
      the term "compartment syndrome." After 46 cases were excluded for missing
      information or irrelevancy, 139 cases were reviewed. The effects of plaintiff
      demographics, mechanism of injury, and complications were assessed. RESULTS: Of
      139 cases, 37 (27%) were settled, 69 (50%) resulted in a defendant ruling, and 33
      (24%) resulted in a plaintiff ruling. Juries were more likely to rule in favor of
      juvenile plaintiffs than adult patients (P = 0.002) and female plaintiffs than
      male plaintiffs (P = 0.008), but indemnity payments were not affected by the age
      or sex of the plaintiff. Plaintiffs who experienced acute compartment syndrome as
      a complication of surgery were more likely to win their suit and receive higher
      awards (P < 0.05), compared with those in whom the condition developed as a
      result of trauma. Amputation or delay in diagnosis or treatment did not affect
      plaintiff verdicts or awards. CONCLUSION: Defendants were more likely to lose a
      lawsuit concerning the management of acute compartment syndrome if the patient
      was a woman or child or if acute compartment syndrome developed as a complication
      of a surgical procedure.

PMID- 28489716
TI  - The Medicare Access and CHIP Reauthorization Act (MACRA) of 2015: What's New?
AB  - The Centers for Medicare and Medicaid Services (CMS) released its Final Rule on
      the Medicare Access and CHIP [Children's Health Insurance Program]
      Reauthorization Act (MACRA) in November 2016. The Rule finalizes the details of
      the merit-based incentive payment system (MIPS) and the alternative payment model
      (APM), which will now collectively be referred to as the Quality Payment Program
      (QPP). This article offers the orthopaedic community a summary of the alterations
      in healthcare policy that will affect practices nationwide.

PMID- 28489718
TI  - Early Life Origins of Hearing Impairment in Older People.

PMID- 28489717
TI  - Coliphages and Gastrointestinal Illness in Recreational Waters: Pooled Analysis
      of Six Coastal Beach Cohorts.
AB  - BACKGROUND: Coliphages have been proposed as indicators of fecal contamination in
      recreational waters because they better mimic the persistence of pathogenic
      viruses in the environment and wastewater treatment than fecal indicator
      bacteria. We estimated the association between coliphages and gastrointestinal
      illness and compared it with the association with culturable enterococci.
      METHODS: We pooled data from six prospective cohort studies that enrolled coastal
      beachgoers in California, Alabama, and Rhode Island. Water samples were collected
      and gastrointestinal illness within 10 days of the beach visit was recorded.
      Samples were tested for enterococci and male-specific and somatic coliphages. We
      estimated cumulative incidence ratios (CIR) for the association between swimming
      in water with detectable coliphage and gastrointestinal illness when human fecal
      pollution was likely present, not likely present, and under all conditions
      combined. The reference group was unexposed swimmers. We defined continuous and
      threshold-based exposures (coliphage present/absent, enterococci >35 vs. <=35
      CFU/100 ml). RESULTS: Under all conditions combined, there was no association
      between gastrointestinal illness and swimming in water with detectable coliphage
      or enterococci. When human fecal pollution was likely present, coliphage and
      enterococci were associated with increased gastrointestinal illness, and there
      was an association between male-specific coliphage level and illness that was
      somewhat stronger than the association between enterococci and illness. There
      were no substantial differences between male-specific and somatic coliphage.
      CONCLUSIONS: Somatic coliphage and enterococci had similar associations with
      gastrointestinal illness; there was some evidence that male-specific coliphage
      had a stronger association with illness than enterococci in marine waters with
      human fecal contamination.

PMID- 28489719
TI  - Microkeratome-Assisted Anterior Lamellar Keratoplasty for the Correction of High
      Degree Postkeratoplasty Astigmatism.
AB  - PURPOSE: To describe the surgical technique and report the outcomes of patients
      treated with microkeratome-assisted anterior lamellar keratoplasty (MALK) for the
      correction of high-degree postkeratoplasty astigmatism. METHODS: Four eyes of 2
      patients with extremely high (>10 D) and irregular [surface asymmetry index >1.0
      D] post-penetrating keratoplasty astigmatism occurring after complete suture
      removal underwent MALK and were followed for at least 3 years after the
      procedure. In all cases, 250-um lamellar keratectomy was performed, followed by 2
      full-thickness incisions through the penetrating keratoplasty scar and the
      placement of an appropriately sized donor graft, which was secured with a double
      running 10-0 nylon suture. All sutures were removed in all eyes within 1 year
      from surgery. Corrected distance visual acuity, refraction, corneal topography,
      and endothelial cell density were noted at each examination. RESULTS: At the last
      follow-up examination (3 years or longer after MALK), corrected distance visual
      acuity had improved to 20/20, refractive astigmatism had decreased to an average
      of 2.1 D (in all cases within 4.5 D), and the average surface asymmetry index had
      reduced from 2.27 to 0.56. CONCLUSIONS: MALK is an effective and safe technique
      for the correction of high-degree postkeratoplasty astigmatism.

PMID- 28489720
TI  - Expression of Peroxiredoxin 2 and Vascular Endothelial Growth Factor Receptor 2
      in Pterygium.
AB  - PURPOSE: The expression of peroxiredoxin 2 and vascular endothelial growth factor
      receptor 2 (VEGFR2) was detected in pterygium to investigate whether they are
      involved in the pathogenesis or recurrence of pterygium and to evaluate the
      association between peroxiredoxin 2 and VEGFR2 in pterygium. METHODS: Ten normal
      bulbar conjunctivae, 35 primary pterygia, and 35 recurrent pterygia were
      obtained. Formalin-fixed, paraffin-wax-embedded tissues were analyzed by
      immunohistochemistry with peroxiredoxin 2 and VEGFR2 antibodies. RESULTS: There
      was no statistical difference between primary pterygia and recurrent pterygia in
      terms of age and sex (P = 0.685; P = 0.811). The expression rate of peroxiredoxin
      2 (94.3%, 66/70) and VEGFR2 (61.4%, 43/70) was increased in pterygia compared
      with normal conjunctivae (negative). The expression of peroxiredoxin 2 in
      recurrent pterygia (negative 0, weak 0, moderate 27, strong 8) was higher than
      that in primary pterygia (negative 6, weak 16, moderate 13, strong 0) (P <
      0.001). The expression of VEGFR2 in recurrent pterygia (negative 4, weak 5,
      moderate 12, strong 4) was higher than that in primary pterygia (negative 23,
      weak 10, moderate 1, strong 1) (P < 0.001). The expression of peroxiredoxin 2 was
      consistent with that of VEGFR2 in pterygium (r = 0.348, P = 0.006). CONCLUSIONS:
      Overexpression of peroxiredoxin 2 and VEGFR2 in pterygium might be involved in
      the pathogenesis or recurrence of pterygium. The increase of VEGFR2 might be
      related to the increase of peroxiredoxin 2 in response to excessive reactive
      oxygen species from ultraviolet exposure.

PMID- 28489721
TI  - Tear Cytokine Levels in Contact Lens Wearers With Acanthamoeba Keratitis.
AB  - PURPOSE: To determine differences in key tear film cytokines between mild and
      severe cases of acanthamoeba keratitis (AK) and control contact lens (CL)
      wearers. METHODS: This was a prospective study of CL wearers with AK attending
      Moorfields Eye Hospital and control CL wearers from the Institute of Optometry,
      London. Basal tear specimens were collected by 10-MUL capillary tubes (BLAUBRAND
      intraMark, Wertheim, Germany), and tear protein levels were measured with a
      multiplex magnetic bead array (Luminex 100; Luminex Corporation, Austin, TX) for
      cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-17A, IL-17E, IL-17F, IL
      22, and interferon gamma and with enzyme-linked immunosorbent assay (Abcam,
      Cambridge, United Kingdom) for CXCL2. Severe cases of AK were defined as having
      active infection for over 12 months and at least 1 severe inflammatory event.
      RESULTS: One hundred and thirty-two tear samples were collected from a total of
      61 cases (15 severe and 46 mild-moderate) and 22 controls. IL-8, part of the Toll
      like receptor 4 cytokine cascade, was found to be expressed at a detectable level
      more often in cases of AK than in control CL wearers (P = 0.003) and in higher
      concentrations in severe cases than in milder forms of the disease (z = -2.35).
      IL-22, part of the IL-10 family, and a proinflammatory Th17 cytokine, was
      detected more often in severe cases than in milder forms of AK (P < 0.02).
      CONCLUSIONS: Profiling patients with AK during disease shows differences in
      cytokine levels between severe and milder disease that may inform clinical
      management. The Toll-like receptor 4 and IL-10/Th17 inflammatory pathways should
      be included in further investigations of this disease.

PMID- 28489722
TI  - Bilateral Herpetic Keratitis After Bilateral Intravitreal Bevacizumab for
      Exudative Macular Degeneration.
AB  - PURPOSE: To report a case of bilateral herpetic epithelial keratitis after
      bilateral intravitreal bevacizumab injections for the treatment of exudative age
      related macular degeneration. METHODS: A 66-year-old man with diabetes and an
      extensive history of bilateral anti-vascular endothelial growth factor treatments
      for exudative age-related macular degeneration received an intravitreal
      bevacizumab injection in the right eye and triple therapy (bevacizumab,
      photodynamic therapy, and triamcinolone acetonide) in the left eye. After 4 days,
      he presented with pain, photophobia, tearing, and decreased vision in both eyes.
      Slit-lamp examination revealed bilateral dendritic epithelial lesions with
      terminal bulbs, and he was diagnosed with bilateral herpes simplex epithelial
      keratitis. RESULTS: The patient was treated with ganciclovir ophthalmic ointment
      and oral acyclovir with resolution of signs and symptoms. CONCLUSIONS: To our
      knowledge, this is the first documented account of bilateral herpetic epithelial
      keratitis after bilateral intravitreal bevacizumab injections.

PMID- 28489723
TI  - Femtosecond Laser Assisted Pterygium Surgery.
AB  - PURPOSE: Pterygium is a prevalent ocular surface disorder. Conjunctival
      autografting (CAG) after pterygium resection is the gold standard treatment.
      Thinner CAGs without Tenon tissue provide better results but are technically
      difficult to achieve. We report on the first femtosecond laser (FSL)-assisted
      pterygium surgery (FLAPS) in humans. METHODS: In a clinical trial, we treated 6
      eyes of 5 patients with FLAPS. After manual removal of the pterygium, CAGs were
      dissected with the Ziemer Z8 at 60-MUm depth and glued into the resection defect.
      CAG thickness and diameter were measured. RESULTS: The CAG area measured 17.9%
      smaller than the laser settings (P = 0.03). Central (75.6 +/- 13.7 MUm) and
      peripheral (77.7 +/- 13.2 MUm) CAG thickness did not differ significantly (P =
      0.3). No buttonholes or CAG tags occurred. The mean dissection time was 19.5 +/-
      1.2 seconds, and the time to remove the FSL-prepared CAG and to unfold it onto
      the cornea was 10.3 +/- 3.8 seconds. During 35.8 +/- 38.0 days of follow-up, no
      postoperative complication or recurrences occurred. The conjunctival epithelium
      had healed at the CAG resection site within 1 week with no evidence of scarring.
      CONCLUSIONS: FLAPS is a new technique, in which the preparation of an ultrathin
      CAG is done by the FSL. After optimization in porcine eyes, the clinical trial in
      the first 6 eyes was performed without any complications and the FSL might assist
      in further standardizing the surgical procedure. Longer follow-up and larger
      cohorts are needed to assess recurrence rates.

PMID- 28489724
TI  - Social Support, Unstable Angina, and Stroke as Predictors of Depression in
      Patients With Coronary Heart Disease.
AB  - BACKGROUND: Depression is known to adversely affect coronary heart disease
      patients in western countries; however, no study of social support and depression
      has been conducted in the Chinese population. OBJECTIVE: The aim of this study
      was to investigate the predictors of depression in patients with coronary heart
      disease. METHODS: Between January and December 2015, a cross-sectional sample of
      105 Taiwanese patients from cardiology units completed a demographic and clinical
      characteristics questionnaire, Enhancing Recovery in Coronary Heart Disease
      Social Support Inventory, and Patient Health Questionnaire-9. RESULTS: Thirty
      nine percent of the participants reported low social support, and 61.0% had
      depression symptoms. Eight factors predicted depression. Social support was
      significantly and adversely correlated with depression (r = -.481, P < .01). The
      other 7 factors were positively correlated with depression: age (r = .212, P <
      .05), reported monthly income of less than US $600 (F = 4.98, P = .001), lack of
      exercise (F = 3.75, P = .027), history of stroke (t = -2.45, P = .016) and kidney
      disease (t = -2.41, P = .018), unstable angina (F = 3.56, P = .031), and groin
      puncture (F = 3.27, P = .042). A hierarchical regression model explained 43.7% of
      the variance in depression. CONCLUSION: Social support, unstable angina, and
      stroke may be important predictors of depression in patients with coronary heart
      disease. These findings help clinical staff to understand physical and mental
      health problems in cardiovascular patients. Thus, we suggest that early
      depression prediction and sufficient social support can help patients to face
      their disease and thus improve depression and health care quality.

PMID- 28489725
TI  - Dog Ownership and Dog Walking: The Relationship With Exercise, Depression, and
      Hopelessness in Patients With Ischemic Heart Disease.
AB  - BACKGROUND: Dog ownership has been associated with increased physical activity in
      the general adult population. OBJECTIVE: The objective of this study was to
      examine dog ownership and dog walking and their relationship with home-based and
      phase II cardiac rehabilitation exercise, depression, and hopelessness in
      patients with ischemic heart disease. METHODS: A total of 122 patients with
      ischemic heart disease were included in this prospective observational study.
      Patients completed dog ownership/walking questions during their hospitalization.
      The Cardiac Rehabilitation Exercise Participation Tool, Patient Health
      Questionnaire-9, and State-Trait Hopelessness Scale were completed by mail at 3,
      8, or 12 months later. Regression modeling was used to evaluate the significance
      of dog ownership/walking on exercise, depression and hopelessness. RESULTS: The
      sample was 34.4% female and had a mean age of 64.7 +/- 9.1 years. Forty-two
      patients (34.4%) reported owning a dog. Patients who owned but did not walk their
      dog reported significantly lower levels of home exercise compared with patients
      who walked their dogs at least 1 day per week (36.8% for non-dog walkers vs 73.9%
      for dog walkers, P = .019). The odds of participating in home exercise were
      significantly higher for dog walkers compared with non-dog walkers (odds ratio,
      8.1 [1.7, 38.5] vs 1.0). There were no differences in phase II cardiac
      rehabilitation exercise, depression, or hopelessness between dog owners and non
      dog owners or between dog walkers and non-dog walkers. CONCLUSIONS: These
      findings show a beneficial effect on home-based exercise for those who dog-walk
      at least 1 day per week. Healthcare professionals should encourage dog walking to
      increase dog owners' physical activity levels.

PMID- 28489726
TI  - A Systematic Review of Interventions to Improve Health Factors or Behaviors of
      the Cardiovascular Health of Prisoners During Incarceration.
AB  - BACKGROUND: Prisoners are disproportionately affected by cardiovascular disease
      and its risk factors. However, primary prevention of cardiovascular disease in
      correctional settings has been widely neglected, and there is little information
      on interventions to improve the cardiovascular health of prisoners while
      incarcerated. OBJECTIVE: The aim of this study was to systematically review
      published literature to identify interventions to improve the health factors or
      behaviors of the cardiovascular health of prisoners during incarceration.
      METHODS: Selected databases were searched using terms related to prisoners and
      cardiovascular disease. Studies were included if they had prisoners as
      participants and measured outcomes of cardiovascular health. Narrative synthesis
      was used to organize the evidence from the studies. RESULTS: Twelve articles
      detailing 11 studies were identified. Most of the studies involved only men.
      Interventions were classified into 4 types: structured physical activity,
      nutrition, mixed with physical activity and educational sessions, and smoking
      cessation. Most studies measured short-term outcomes relating to cardiovascular
      health such as changes in blood pressure and weight. Only 4 studies were of high
      quality. Structured physical activity interventions, nutrition interventions, and
      smoking cessation interventions delivered in a group setting had significant
      effects on at least 1 measured outcome. The effect of mixed interventions could
      not be determined. CONCLUSIONS: Structured physical activity interventions,
      nutrition interventions, and smoking cessation interventions delivered in a group
      setting can improve health factors or behaviors of the cardiovascular health of
      prisoners during incarceration. More high-quality research is needed to increase
      the evidence base on the effectiveness of these interventions in the correctional
      setting.

PMID- 28489727
TI  - Pharmacology of Thiopurine Therapy in Inflammatory Bowel Disease and Complete
      Blood Cell Count Outcomes: A 5-Year Database Study.
AB  - BACKGROUND: Thiopurines are the prerequisite for immunomodulation in inflammatory
      bowel disease (IBD) therapy. When administered in high (oncological) dose,
      thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and
      myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted
      to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the
      most common adverse events of thiopurines. The aim of this study was to assess
      the effect of thiopurine metabolites on hematologic and hepatic parameters and to
      determine which patient characteristics are related to generation of thiopurine
      metabolites. METHODS: The authors scrutinized the therapeutic drug monitoring
      database of the VU University medical center and subsequently merged this
      database with the Clinical Laboratory database of our hospital covering the same
      time period (2010-2015). RESULTS: The authors included 940 laboratory findings of
      424 unique patients in this study. Concentrations of 6-thioguanine nucleotides (6
      TGN) correlated negatively with red blood cell count, white blood cell count, and
      neutrophil count in both azathioprine (AZA) and mercaptopurine users. There was a
      positive correlation with mean corpuscular volume. In patients using 6
      thioguanine, 6-TGN concentrations correlated positively with white blood cell
      count. Furthermore, there was an inverse correlation between patient's age and 6
      TGN concentrations in patients using AZA or 6-thioguanine, and we observed an
      inverse correlation between body mass index and 6-TGN concentrations in patients
      using AZA or mercaptopurine. No relations were observed with liver test
      abnormalities. CONCLUSIONS: Thiopurine derivative therapy influenced bone marrow
      production and the size of red blood cells. Age and body mass index were
      important pharmacokinetic factors in the generation of 6-TGN.

PMID- 28489728
TI  - Novel Adjunct Drugs Reverse Endothelial Glycocalyx Damage After Hemorrhagic Shock
      in Rats.
AB  - INTRODUCTION: There is interest in the small-volume therapeutic use of adjunct
      drugs for treating hemorrhagic shock (HS). However, critical information is only
      partially available on mechanisms of action of promising compounds such as
      adenosine-lidocaine-magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M),
      and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these
      adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx
      and hemodynamics. METHODS: After baseline, 40% of total blood volume was removed
      from 44 anesthetized Sprague-Dawley male rats. One hour after hemorrhage, animals
      were resuscitated using ALM, BHB/M, or P-188 followed by lactated Ringer's (LR,
      15 mL/kg). Control animals were not treated (SHAM) or received LR alone. Sampled
      blood was used to quantify shed syndecan-1 in plasma; multiple systemic
      physiological parameters were recorded. In vivo glycocalyx thickness,
      microvascular permeability, and microhemodynamics were evaluated in >200
      cremaster venules using intravital videomicroscopy. RESULTS: Compared with
      baseline, resuscitation using adjuncts was associated with glycocalyx restoration
      of 97 +/- 9% (ALM), 75 +/- 8% (BHB/M), and 85 +/- 5% (P-188): significantly
      higher than LR-only (56 +/- 4%). Significantly better permeability, similar to
      SHAM values, was measured after ALM and P-188, and low plasma syndecan-1 levels
      were measured after resuscitation with all adjuncts. Microhemodynamic changes
      were relatively small while systemic parameters such as mean arterial pressure
      and lactate improved but remained below or above the baseline, respectively, as
      expected from this hypotensive resuscitation model. CONCLUSION: The drugs ALM,
      BHB/M, and P-188 provide beneficial effects as adjuncts to hypotensive
      resuscitation in this HS model by mechanisms involving changes at the
      microvascular level including the glycocalyx.

PMID- 28489729
TI  - Trends in ART Prescription and Viral Suppression Among HIV-Positive Young Adults
      in Care in the United States, 2009-2013.
AB  - BACKGROUND: Only 13% of HIV-positive young adults are estimated to be virally
      suppressed and, even among those receiving medical care, HIV-positive young
      adults are less likely than older adults to take antiretroviral therapy (ART), be
      adherent, and be virally suppressed. We sought to examine trends in treatment and
      health outcomes from 2009 to 2013 among HIV-positive young adults (aged 18-24
      years) in care. SETTING: The Medical Monitoring Project is a complex sample
      survey of HIV-infected adults receiving medical care in the United States.
      METHODS: We used weighted interview and medical record data collected from June
      2009 to May 2014 to estimate trends in the prevalence of ART prescription,
      adherence, side effects, single-tablet ART regimens, regular care utilization,
      and viral suppression among young adults. RESULTS: From 2009 to 2013, there were
      significant increases in ART prescription (76%-87%) and the proportion of young
      adults taking ART who reported taking single-tablet regimens (49%-62%). There was
      no significant change in adherence, side effects, or regular care utilization.
      Although viral suppression at last test did not change (65% at both time
      periods), the proportion of young adults who were sustainably virally suppressed
      significantly increased (29%-46%). Accounting for ART prescription and single
      tablet regimen use attenuated the sustained viral suppression trend. CONCLUSIONS:
      Although the level of viral suppression among young adults in care remains
      suboptimal, the observed increases in ART prescription and sustained viral
      suppression may be a cause for optimism regarding efforts to improve outcomes for
      this vulnerable population.

PMID- 28489730
TI  - Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker
      Assisted Deconvolution.
AB  - OBJECTIVE: Improve pooled viral load (VL) testing to increase HIV treatment
      monitoring capacity, particularly relevant for resource-limited settings. DESIGN:
      We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling
      deconvolution strategy that uses information from low-cost, routinely collected
      clinical markers to determine an efficient order of sequential individual VL
      testing and dictates when the sequential testing can be stopped. METHODS: We
      simulated the use of pooled testing to ascertain virological failure status on
      918 participants from 3 studies conducted at the Academic Model Providing Access
      to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when
      using mMPA and other pooling methods. We also evaluated the impact of practical
      factors, such as specific markers used, prevalence of virological failure, pool
      size, VL measurement error, and assay detection cutoffs on mMPA, other pooling
      methods, and single testing. RESULTS: Using CD4 count as a marker to assist
      deconvolution, mMPA significantly reduces the number of VL assays by 52%
      [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to
      22%) compared with individual testing, simple mini-pooling, and mini-pooling with
      algorithm, respectively. mMPA has higher sensitivity and negative/positive
      predictive values than mini-pooling with algorithm, and comparable high
      specificity. Further improvement is achieved with additional clinical markers,
      such as age and time on therapy, with or without CD4 values. mMPA performance
      depends on prevalence of virological failure and pool size but is insensitive to
      VL measurement error and VL assay detection cutoffs. CONCLUSIONS: mMPA can
      substantially increase the capacity of VL monitoring.

PMID- 28489734
TI  - Treatment of distal splenic artery aneurysm by laparoscopic aneurysmectomy with
      end-to-end anastomosis: A case report.
AB  - RATIONALE: Splenic artery aneurysm (SAA) is the most common visceral artery
      aneurysm, while most SAAs are treated by endovascular or open procedures. PATIENT
      CONCERNS: Here we present a case of SAA treated by laparoscopic aneurysmectomy
      with end-to-end anastomosis. DIAGNOSES: A 40-year-old woman was incidentally
      found to have an asymptomatic distal SAA. CT scan revealed the SAA to be located
      at the hilum of the spleen, with a maximal diameter of 2.7 cm. INTERVENTIONS: To
      prevent sudden rupture, the patient received laparoscopic aneurysmectomy. During
      the operation, end-to-end anastomosis was also performed since a tortuous
      proximal splenic artery prevented delivery of the stent graft. OUTCOMES: The
      patient was ambulated 12 hours after surgery and discharged 5 days later.
      Postoperative recovery was smooth without hemorrhage, infarction, infection, or
      splenic artery thrombosis. At 10-month follow-up,no hemorrhage, aneurysm
      recurrence, spleen infarction, splenic artery stenosis, or thrombosis had
      occurred. LESSONS: Patients with distal SAA can be treated by laparoscopic
      aneurysmectomy with end-to-end anastomosis to preserve the spleen. The
      laparoscopic procedure is safe and feasible in the selected patients.

PMID- 28489735
TI  - Impact of a preoperative conversational hypnotic session on propofol consumption
      using closed-loop anesthetic induction guided by the bispectral index: A
      randomized controlled trial.
AB  - OBJECTIVE: The automated administration of propofol in a closed loop could be
      used to objectively evaluate the nonpharmacological anesthetic action of
      hypnotherapy. The objective of this study was to evaluate the impact of a
      conversational hypnosis session on the consumption of propofol for anesthetic
      induction. DESIGN: A randomized, usual care-controlled, single-center, patient
      blind trial. SETTING: Tertiary care center in France from November 2012 to
      December 2013. PARTICIPANTS: Adult patients scheduled for a surgical procedure
      under general anesthesia. INTERVENTIONS: Before surgery, patients were randomized
      with a computer-generated random list for a preoperative conversational hypnosis
      session or for usual care. The conversational hypnosis session was conducted and
      individualized by the therapist with an academic degree in hypnosis in a quiet
      environment. Anesthetic induction was automatically performed by propofol without
      opioids and was assisted by the bispectral index in a closed loop. OUTCOME:
      Primary endpoint was the propofol dose required for anesthesia induction, defined
      as a Bispectral index less than 60 for at least 30 seconds. RESULTS: The study
      included 48 patients in the hypnosis group and 49 patients in the control group.
      No difference in propofol consumption to obtain anesthesia induction was observed
      between the groups (total dose: 138.6 [67.5] and 130 [47.9] mg, P = .47; adjusted
      dose: 2.15 [1.09] and 1.95 [0.66] mg/kg, P = .28, for the hypnosis and control
      groups, respectively). Hetero-evaluation of arm movement during propofol
      injection (no reaction: 98% and 74%; P = .004, in the hypnosis and control
      groups, respectively) and face reaction at venous access placement (no reaction
      59% and 30%; P = .017, in the hypnosis and control groups, respectively) were
      lower in the hypnosis group. No adverse event was reported. CONCLUSIONS: No
      difference in propofol consumption was observed in this study designed to
      evaluate the effect of a hypnotic conversational session on anesthesia induction
      using an automated tool for propofol administration.

PMID- 28489732
TI  - Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for
      Neonates.
AB  - BACKGROUND: Nevirapine (NVP) is a key component of antiretroviral prophylaxis and
      treatment for neonates. We evaluated current World Health Organization (WHO)
      weight-band NVP prophylactic dosing recommendations and investigated optimal
      therapeutic NVP dosing for neonates. METHODS: The PHPT-5 study in Thailand
      assessed the efficacy of "Perinatal Antiretroviral Intensification" to prevent
      mother-to-child transmission of HIV in women with <8 weeks of antiretroviral
      treatment before delivery (NCT01511237). Infants received a 2-week course of
      zidovudine/lamivudine/NVP (NVP syrup/once daily: 2 mg/kg for 7 days; then 4 mg/kg
      for 7 days). Infant samples were assessed during the first 2 weeks of life. NVP
      population pharmacokinetics (PK) parameters were estimated using nonlinear mixed
      effects models. Simulations were performed to estimate the probability of
      achieving target NVP trough concentrations for prophylaxis (>0.10 mg/L) and for
      therapeutic efficacy (>3.0 mg/L) using different infant dosing strategies.
      RESULTS: Sixty infants (55% male) were included. At birth, median (range) weight
      was 2.9 (2.3-3.6) kg. NVP concentrations were best described by a 1-compartment
      PK model. Infant weight and postnatal age influenced NVP PK parameters. Based on
      simulations for a 3-kg infant, >=92% would have an NVP trough >0.1 mg/L after 48
      hours through 2 weeks using the PHPT-5 and WHO-dosing regimens. For NVP-based
      therapy, a 6-mg/kg twice daily dose produced a trough >3.0 mg/L in 87% of infants
      at 48 hours and 80% at 2 weeks. CONCLUSION: WHO weight-band prophylactic
      guidelines achieved target concentrations. Starting NVP 6 mg/kg twice daily from
      birth is expected to achieve therapeutic concentrations during the first 2 weeks
      of life.

PMID- 28489736
TI  - Primary pulmonary meningioma: A case report.
AB  - RATIONALE: Primary extracranial meningiomas are rare outside the head and neck
      region. PATIENT CONCERNS: A 44-year-old female patient had chest pain for more
      than 1 year. DIAGNOSES: Preoperative chest computed tomography (CT) scan revealed
      a nodule in the right lower lobe, 1.8 cm in diameter. Tumor tissues were examined
      by immunohistochemistry for vimentin and S-100. INTERVENTIONS:
      Histopathologically, the tumor was characterized by whorled nests of spindle
      shaped cells accompanied by psammoma bodies. Immunohistochemistry demonstrated
      tumor cell positivity for vimentin and S-100. This case was diagnosed as a
      primary pulmonary meningioma. The tumor was removed by a thoracoscopic pulmonary
      wedge resection. OUTCOMES: Postoperative cranial and spinal CT scan did not show
      any intracranial or spinal mass. No recurrence of the tumor was reported at the
      time of writing up this case report. LESSONS: A primary pulmonary meningioma
      should be considered in the differential diagnosis workup of pulmonary nodules.

PMID- 28489737
TI  - Clinical effect of montelukast sodium combined with inhaled corticosteroids in
      the treatment of OSAS children.
AB  - This study was designed to investigate the clinical effect of montelukast sodium
      combined with inhaled corticosteroids in the treatment of children with
      obstructive sleep apnea syndrome (OSAS).One hundred ninety-five children were
      enrolled and divided into 3 groups: groups A, B, and C; the group A (oral use of
      montelukast sodium), group B (nasal spray of mometasone furoate), and group C
      (oral use of montelukast sodium + nasal spray of mometasone furoate). Telephone
      questionnaire surveys were carried out. Polysomnography monitoring was performed
      and lateral x-ray radiographs of the cervical spine were taken before treatment
      and at 12 weeks after treatment. The improvement of clinical symptoms after
      treatment and its effective rate were analyzed. The difference in clinical
      characteristics between groups C1 and C2 was analyzed.In the 3 groups, clinical
      symptoms improved at 12 weeks after treatment compared with before (P < .05 or P
      < .01). Apnea-hypopnea index value decreased (P < .05) and minimal SaO2 increased
      (P < .05), while adenoidal/nasopharyngeal ratio was reduced (P < .05). Compared
      with groups A and B, group C had a shortened response duration of snoring, apnea,
      and restless sleep (P < .05). Differences in the response duration of buccal
      respiration and hyperhidrosis were not statistically significant (P > .05). The
      total effective rate was higher in group C than in A and B (P < .05), while the
      differences in all indices between groups A and B were not statistically
      significant (P > .05). The difference in the grade of the size of the tonsil
      between groups C1 and C2 was statistically significant (P < .05).The total
      effective rate of the combined treatment was higher than that of the single use
      of any of the 2 drugs, which allowed the rapid relief of symptoms. Drug treatment
      may have a poor curative effect in the treatment of OSAS patients with >= grade 3
      tonsil hypertrophy.

PMID- 28489738
TI  - Inhibitory member of the apoptosis-stimulating protein of p53 is overexpressed in
      bladder cancer and correlated to its progression.
AB  - Several lines of direct evidence show that inhibitory member of the apoptosis
      stimulating protein of p53 (iASPP) has an important function in cancer
      progression. However, its expression pattern and relationship with clinical
      pathologic characteristics in bladder cancer (BC) have not been completely
      elucidated. In this study, firstly, samples from 3 patients with invasive BC were
      detected by liquid chromatography tandem mass spectrometry to confirm
      overexpression of iASPP in BC, then samples from patients with noninvasive and
      invasive BC were detected by real-time polymerase chain reaction, Western blot,
      and tissue microarry immunohistochemistry. The relationship between iASPP
      expression and various clinicopathological features was investigated. The results
      showed m-RNA and protein of iASPP were overexpressed in BC and the rate of iASPP
      positive cells was positively correlated with Union for International Cancer
      Control-Tumor, Node, Metastases stage, histologic grade, lymph node metastasis
      and poor overall survive. The data demonstrate that iASPP is overexpressed in BC
      and promotes the malignancy of BC. iASPP maybe serve as a potential therapeutic
      target for BC.

PMID- 28489739
TI  - Diagnostic accuracy of DWI in patients with ovarian cancer: A meta-analysis.
AB  - BACKGROUND: Diffusion weighted imaging (DWI) is recently developed for
      identifying different malignant tumors. In this article the diagnostic accuracy
      of DWI for ovarian cancer was evaluated by synthesis of published data. METHODS:
      A comprehensive literature search was conducted in PubMed/MEDLINE and Embase
      databases on the diagnostic performance of DWI for ovarian cancer published in
      English. Methodological quality was evaluated following Quality Assessment for
      Studies of Diagnostic Accuracy 2 (QUADAS 2) tool. We adopted the summary receiver
      operating characteristic (SROC) curve to assess the DWI accuracy. RESULTS: Twelve
      studies including 1142 lesions were analyzed in this meta-analysis to estimate
      the pooled Sen (sensitivity), Spe (specificity), PLR (positive likelihood ratio),
      NLR (negative likelihood ratio), and construct SROC (summary receiver operating
      characteristics) curve. The pooled Sen and Spe were 0.86 (95% confidence interval
      [CI], 0.83-0.89) and 0.81 (95%CI, 0.77-0.84), respectively. The pooled PLR and
      pooled NLR were 5.07 (95%CI, 3.15-8.16) and 0.17 (95%CI, 0.10-0.30),
      respectively. The pooled diagnostic odds ratio (DOR) was 35.23 (95%CI, 17.21
      72.14). The area under the curve (AUC) was 0.9160. CONCLUSION: DWI had moderately
      excellent diagnostic ability for ovarian cancer and promised to be a helpful
      diagnostic tool for patients of ovarian cancer.

PMID- 28489740
TI  - Percutaneous pinning after prolonged skeletal traction with the hip in a flexed
      position for unstable slipped capital femoral epiphysis: A case series of 11
      patients.
AB  - BACKGROUND: Unstable slipped capital femoral epiphysis (SCFE) has a relatively
      high risk of avascular necrosis of the femoral head. Standard treatment for
      unstable SCFE is still controversial. We reviewed unstable SCFE case series
      treated with the standardized protocol, which consisted of percutaneous pinning
      after prolonged skeletal traction. METHODS: Our treatment regimen for unstable
      SCFE patients included 1 week or more of skeletal traction with the hip in a
      flexed position of 45 degrees, and subsequent percutaneous pinning after
      unintentional reduction. Eleven patients were treated in our institution and an
      affiliated hospital between 2003 and 2013. Sex, age at surgery, body mass index,
      the presence of hormonal abnormality, duration between onset and surgery, head
      shaft angle, posterior tilting angle, and modified Harris hip score were
      investigated from the medical records and radiographs. RESULTS: There were 8 male
      and 3 female with an average age of 11.7 years and an average body mass index of
      24.5 kg/mm. No patients had hormonal abnormalities. The duration between onset
      and surgery ranged from 8 to 16 days. The average preoperative and postoperative
      head shaft angles were 126 and 141 degrees, respectively. Postoperative posterior
      tilting angle was averaged of 30.7 degrees, which decreased to 21.5 degrees
      during follow-up period. One patient showed mild avascular necrosis only
      confirmed by magnetic resonance imaging, but he was uneventfully treated without
      additional procedures. As a result, all patients had a perfect modified Harris
      hip score of 91 points. CONCLUSIONS: Prolonged traction with the hip in a flexed
      position may not only provide gradual reduction of posteriorly displaced
      epiphysis but also decrease intra-articular pressure before surgery. Although
      percutaneous pinning after unintentional reduction leaves mild displacement of
      the femoral epiphysis, remodeling could be expected during remaining growth
      period.

PMID- 28489741
TI  - Salmonella enterica serovar Panama meningitis in exclusive breastfeeding infants:
      Report of 4 cases, clinical features and therapeutic challenges.
AB  - RATIONALE: The pathway of Nontyphoid Salmonella meningitis, especially in
      exclusive breastfeeding infants, has not been well characterized. PATIENT
      CONCERNS: We analyzed data related to nontyphoid Salmonella meningitis in 4
      infants. DIAGNOSES: No diarrhea was observed and the coproculture was negative
      for all patients. INTERVENTIONS: Early diagnosis and treatment with combination
      of third-generation cephalosporins plus quinolones for a minimum of 3 weeks is
      necessary to avoid severe sequelae and death. OUTCOMES: The first 3 patients had
      a good evolution, whereas the last patient had multiple brain abscesses and
      hydrocephalus requiring treatment with a ventriculoperitoneal shunt. LESSONS: The
      highlights of our study are that all infants were exclusively breastfed, no
      diarrhea observed and the negative coproculture for all the 4 patients, which is
      relatively rare for Salmonella infection.

PMID- 28489743
TI  - Narrow-band imaging endoscopy is advantageous over conventional white light
      endoscopy for the diagnosis and treatment of children with Peutz-Jeghers
      syndrome.
AB  - Using narrow-band imaging (NBI), the micro morphology of polyp surfaces was
      visualized at high resolution when the contrast between the lesions and the
      surrounding tissue areas was intensified. The objective of the study was to
      compare NBI and conventional white light endoscopy (C-WLI) for diagnostic
      efficacy and treatment of children with Peutz-Jeghers syndrome (PJS), a rare
      autosomal dominant-genetic disease.We retrospectively analyzed the clinical data
      of 18 patients diagnosed with PJS and 72 diagnosed with juvenile polyps during
      the same time period. Endoscopy was used to observe the morphology of polyps,
      which were classified according to the Kudo pit pattern. Eighty-two and 76 polyps
      were resected using endoscopy from PJS and juvenile polyp patients, respectively,
      and pathologically examined for comparison with NBI or C-WLI endoscopic
      observations.With NBI, 57 (69.5%) type I, 10 (12.2%) type II, and 13 (15.9%) type
      III polyps were identified in 82 (100%) polyps excised from 18 PJS patients,
      whereas 69 (88.5%) type I, 5 (6.4%) type II and 4 (5.1%) type III were identified
      in 78 (100%) of polyps removed from 72 juvenile polyp patients. The combined
      ratios of types II and III were higher in PJS (28.1%) than in juvenile polyp
      patients (11.5%). Pathological diagnosis identified 69 of 82 PJS polyps as
      hamartoma and 13 as adenoma, whereas NBI detected 10 adenomas and C-WLI only 4.
      The sensitivity, specificity, and accuracy of NBI in the diagnosis of adenoma
      were 76.9%, 97.1%, and 93.9%, respectively, whereas those of C-WLI were 30.8%,
      94.2%, and 84.1%.NBI endoscopy had higher sensitivity and specificity than C-WLI
      for the diagnosis of adenomatous polyps and is recommended for the diagnosis,
      characterization, and resection of polyps in children with PJS.

PMID- 28489742
TI  - Circulating TNF receptors predict cardiovascular disease in patients with chronic
      kidney disease.
AB  - Cardiovascular disease (CVD) is the main public health problem in patients with
      chronic kidney disease (CKD); however, there is no established biomarker for
      predicting CVD morbidity and mortality in CKD. The aim of this study was to
      evaluate the role of circulating tumor necrosis factor receptors (cTNFRs) in
      predicting CVD risk in CKD patients.We prospectively recruited 984 patients with
      CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were
      determined by performing an enzyme-linked immunosorbent assay. During the mean
      follow-up period of 4 years, 36 patients experienced a CVD event. The median
      serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0
      (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated
      with the cTNFR2 level (r = 0.86, P < .0001). The urinary protein-to-creatinine
      ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly
      correlated with the cTNFR2 level (r = 0.21 for UPCR, r = -0.67 for eGFR; P < .001
      for all). Similar correlations were observed for serum cTNFR1 (r = 0.21 for UPCR,
      r = -0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses,
      cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P =
      .016) and cTNFR2 (HR 4.156, 95% CI 1.913-9.030, P < .001) predicted CVD risk even
      after adjustment for clinical covariates, such as UPCR, eGFR, and high
      sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other
      risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be
      relevant predictors of CVD in CKD patients.

PMID- 28489745
TI  - Adverse local tissue reaction after 2 revision hip replacements for ceramic liner
      fracture: A case report.
AB  - INTRODUCTION: In younger patients, ceramic-on-ceramic (CoC) bearing surfaces are
      usually recommended for total hip replacement (THR) because of their low wear
      rate and longer expected functional life. Although technical advancements have
      reduced the risk of ceramic bearings fracture, this complication remains a major
      concern. CASE DESCRIPTION: We present the case of a 56-year-old patient
      undergoing 3 revision hip arthroplasties of the right hip due to ceramic liner
      fractures. Initial THR (2008) was performed with a CoC bearing, followed by liner
      fracture due to trauma a year later. The acetabular component and liner were
      replaced, with a minor incongruence between the old head and new insert. The 2nd
      ceramic insert fractured 3.5 years later, following minor trauma. Upon revision,
      the bearing surface was changed to metal-on-polyethylene (MoP). The performed
      retrieval analysis demonstrated stripe and rim wear, and evidence of adhesive
      wear. The patient was referred to us a month later, with a fistula on the lateral
      side of the hip, discharging black, petroleum-like liquid. Radiology showed well
      fixed implants, no dislocation and no apparent polyethylene wear. Microbiological
      assessment of the discharge showed no infection. Intraoperatively massive
      metallosis was noticed, with stable acetabular and femoral components. The metal
      femoral head was heavily abraded, with almost 1% volumetric wear. Hematoxylin and
      eosin stained frozen tissue samples showed muscular and adipose tissue necrosis,
      while polarized light microscopy highlighted metal, polyethylene, and ceramic
      particles. CONCLUSION: The present case is yet another report showing the adverse
      outcomes of using MoP bearings for revision after ceramic liner fracture in THR.

PMID- 28489744
TI  - Diagnostic accuracy of SPECT, PET, and MRS for primary central nervous system
      lymphoma in HIV patients: A systematic review and meta-analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis to assess the
      roles of SPECT, PET, and MRS in distinguishing primary central nervous system
      lymphoma (PCNSL) from other focal brain lesions (FBLs) in human immunodeficiency
      virus (HIV)-infected patients. METHODS: PubMed, Scopus, and Medline were
      systematically searched for eligible studies from 1980 to 2016. Two authors
      extracted characteristics of patients and their lesions using predefined
      criteria. RESULTS: Eighteen studies on SPECT containing 667 patients, 6 studies
      on PET containing 108 patients, and 3 studies on MRS containing 96 patients were
      included. SPECT had a pooled sensitivity of 0.92 (95% CI: 0.85-0.96) and
      specificity of 0.84 (95% CI: 0.74-0.90) in differentiating PCNSL from other FBLs.
      For the 6 studies that used only pathology and/or serology as the gold standard,
      the pooled sensitivity was 0.85 (95% CI: 0.72-0.97) and the pooled specificity
      was 0.73 (95% CI: 0.54-0.92). CONCLUSION: SPECT has good diagnostic accuracy for
      discriminating PCNSL from other FBL-causing disorders in HIV patients. However,
      the actual sensitivity and specificity of SPECT may be lower than expected if
      only pathology and/or serology was used as the gold standard. PET may be superior
      but has less supporting clinical data and is more expensive.

PMID- 28489746
TI  - Pediatric esophagopleural fistula: Two case reports and a literature review.
AB  - Esophagopleural fistula (EPF) is rarely reported in children with a high
      misdiagnosis rate. This study aimed to reveal the clinical manifestations and
      managements of EPF in children.Two pediatric cases of EPF in our hospital were
      reported. A bibliographic search was performed on the PubMed, WANFANG, and CNKI
      databases for EPF-related reports published between January 1980 and May 2016.
      The pathogeny, clinical manifestations, diagnosis, treatments, and prognosis of
      EPF patients were collected and discussed.Based on conservative treatments, 1
      pediatric EPF case induced by cervical trauma was cured by longitudinal septum
      incision-mediated drainage. The other pediatric EPF induced by endoscopic balloon
      dilation was cured by dual stent implantation. A total of 38 studies of 197 EPF
      patients (191 adults and 6 children) were reviewed. Latrogenic factor, esophageal
      foreign body, and infection are considered the main causes of EPF in children.
      Unilateral pleural effusion accompanied by food residue was the main
      manifestations of EPF. Chest computed tomography (CT) and contrast esophagography
      were usually used in the diagnosis of EPF with high accuracy. Surgical treatment
      in adults with EPF exhibited a significantly higher cure rate and lower mortality
      rate than conservative treatment (P < .01).Pleural effusion with food residue is
      a specific finding in EPF. Chest CT exhibited high sensitivity for the diagnosis
      of EPF. Conservative treatment may be preferable for pediatric patients with EPF.

PMID- 28489747
TI  - Postoperative changes in the retinal thickness and volume after vitrectomy for
      epiretinal membrane and internal limiting membrane peeling.
AB  - The aim of the study was to investigate the thickness and volume profiles of each
      retinal layer in postoperative patients with epiretinal membranes.Twenty-four
      patients who underwent pars plana vitrectomy with internal limiting membrane
      (ILM) peeling for epiretinal membrane were included. The best corrected visual
      acuity, thickness, and volume were recorded from the medical records through a
      retrospective review. Spectral domain optical coherence tomography was used to
      measure the average thickness and volume of each retinal layer before surgery and
      6 months postoperatively.All 24 patients were monitored for 60 months after
      surgery. In all Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, the
      thickness and volume of the retinal nerve fiber layer and the inner retinal layer
      decreased significantly. In contrast, the thickness and volume of the ganglion
      cell layer, inner nuclear layer, inner plexiform layer, and outer plexiform layer
      only decreased in some ETDRS subfields. Finally, there was no significant change
      in the thickness or volume of the outer nuclear layer (ONL), retinal pigment
      epithelium (RPE), and photoreceptor layers in all ETDRS subfields.The thickness
      and volume of the inner retina layer decreased significantly after pars plana
      vitrectomy using ILM peeling. However, there was no significant change in the
      thickness and volume of the outer retinal layers (ONL, RPE, and photoreceptor)
      after surgery.

PMID- 28489748
TI  - P16 protein expression as a useful predictive biomarker for neoadjuvant
      chemotherapy response in patients with high-grade osteosarcoma: A systematic meta
      analysis under guideline of PRISMA.
AB  - BACKGROUND: Neoadjuvant chemotherapy for patients with high-grade osteosarcoma
      has highly improved the clinical survival. However, the prognostic and predictive
      role of P16 expression after neoadjuvant chemotherapy remains unclear. We first
      determined whether P16 expression can become a potential prognostic and
      predictive biomarker in high-grade osteosarcoma. METHODS: This meta-analysis was
      conducted based on the Preferred Reporting Items for Systematic reviews and Meta
      Analyses (PRISMA) guideline. Eligible studies were pooled and the overall odds
      ratios (ORs) and hazard ratios (HRs) with the corresponding 95% confidence
      intervals (95% CIs) were calculated in this analysis. RESULTS: Four studies
      involving a total of 527 patients with high-grade osteosarcoma receiving
      neoadjuvant chemotherapy were identified. We did not find that P16 expression was
      correlated with sex status, histologic subtype, and tumor site (P > .1). P16
      expression was found to be significantly associated with a "good" response to
      neoadjuvant chemotherapy (OR = 4.69, P < .001). A significant relationship was
      observed between p16 expression and pathologic complete response after
      neoadjuvant chemotherapy using multivariate analysis (OR = 9.63, P = .001). The
      expression of the P16 was not associated with clinical outcomes in overall
      survival (OS) and disease-free survival (DFS) by multivariate analysis (OS: P =
      .448; DFS: P = .263). CONCLUSIONS: The use of P16 expression could become a
      promising predictive biomarker of the response to neoadjuvant chemotherapy in the
      white population with high-grade osteosarcoma. However, it was not correlated
      with the prognosis of patients in OS and DFS. More clinical researches are very
      essential in Asians in the future.

PMID- 28489749
TI  - Association between PAX7 and NTN1 gene polymorphisms and nonsyndromic orofacial
      clefts in a northern Chinese population.
AB  - BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the most common orofacial
      congenital defect with a complex etiology. Genome-wide association studies have
      identified paired box protein 7 (PAX7) and netrin-1 (NTN1) as candidate
      susceptibility genes for NSOC in both European and Asian populations. Here,
      possible associations between single-nucleotide polymorphisms (SNPs) in or near
      PAX7 and NTN1 were investigated in relation to risk of NSOC in a northern Chinese
      population. METHODS: A total of 602 individuals with NSOC and 510 controls were
      recruited from northern China. Polymerase chain reaction-ligation detection
      reactions were used to analyze 4 SNPs (rs742071, rs6659735, rs766325, and
      rs4920520) of PAX7 and 2 SNPs (rs9904526 and rs9788972) of NTN1. Investigations
      of polymorphisms and risk of NSOC were conducted by using the PLINK software.
      RESULTS: NTN1 rs9788972 AG was found to be associated with an increased risk of
      NSOC compared to the GG homozygous genotype (OR = 1.43, 95% CI = 1.11-1.86, P =
      .006). When the multifactor dimensionality reduction method was applied, NTN1
      rs9788972 still exhibited an increased risk for NSOC (P = .008). In contrast,
      SNPs in PAX7 were not associated with any increased risk of NSOC. CONCLUSION:
      NTN1 rs9788972 is identified as a risk locus for NSOC susceptibility in a
      northern Chinese population.

PMID- 28489750
TI  - Performance of the LACE index to identify elderly patients at high risk for
      hospital readmission in Singapore.
AB  - Unplanned readmissions may be avoided by accurate risk prediction and appropriate
      resources could be allocated to high risk patients. The Length of stay, Acuity of
      admission, Charlson comorbidity index, Emergency department visits in past six
      months (LACE) index was developed to predict hospital readmissions in Canada. In
      this study, we assessed the performance of the LACE index in a Singaporean cohort
      by identifying elderly patients at high risk of 30-day readmissions. We further
      investigated the use of additional risk factors in improving readmission
      prediction performance.Data were extracted from the hospital's electronic health
      records (EHR) for all elderly patients >= 65 years, with alive-discharge episodes
      from Singapore General Hospital in 2014. In addition to LACE, we also collected
      patients' data during the index admission, including demographics, medical
      history, laboratory results, and previous medical utilization.Among the 17,006
      patients analyzed, 2051 or 12.1% of them were observed 30-day readmissions. The
      final predictive model was better than the LACE index in terms of discriminative
      ability; c-statistic of LACE index and final logistic regression model was 0.595
      and 0.628, respectively.The LACE index had poor discriminative ability in
      identifying elderly patients at high risk of 30-day readmission, even if it was
      augmented with additional risk factors. Further studies should be conducted to
      discover additional factors that may enable more accurate and timely
      identification of patients at elevated risk of readmissions, so that necessary
      preventive actions can be taken.

PMID- 28489751
TI  - Polyp missing rate and its associated risk factors of referring hospitals for
      endoscopic resection of advanced colorectal neoplasia.
AB  - Missed polyps are frequently observed in surveillance colonoscopy or referral
      resection. We evaluated the polyp missing rate and its associated risk factors in
      patients who were referred to a tertiary hospital for endoscopic resection of
      advanced colorectal neoplasia.A total of 388 patients with advanced neoplasia who
      underwent colonoscopy in their referring hospitals and only endoscopic resection
      without total colonoscopy in Pusan National University Yangsan Hospital from 2009
      to 2014 and who underwent surveillance colonoscopy within 6 to 12 months were
      retrospectively analyzed.The per-patient missing rate for polyps, adenomas, and
      advanced neoplasia in referring hospital were 58.2% (226 cases), 47.2% (183
      cases), and 5.7% (22 cases), respectively. The advanced neoplasia in surveillance
      colonoscopy comprised the following: >=1 cm lesions (11 cases, 50%), high-grade
      dysplasia (4 cases, 18.2%), villous adenoma (4 cases, 18.2%), and invasive cancer
      (3 cases, 13.6%). Risk factors for missed adenomas in multivariate analysis were
      >=60 years (P = .004), male (P <.001), and no usage of the cap-assisted
      colonoscopy (P = .015). Missed polyps/adenomas were most frequent in the
      ascending colon (P <.001).The missing rate for polyps/adenomas of referring
      hospitals was higher than expected. Especially, patients with old age or male, or
      no usage of cap-assisted colonoscopy on initial colonoscopy were at increased
      risk of missed adenoma. Careful complete colonoscopy during referral resection or
      early surveillance colonoscopy is mandatory in the patients with advanced
      colorectal neoplasia and unknown-quality index colonoscopy.

PMID- 28489752
TI  - Enteric hyperoxaluria in chronic pancreatitis.
AB  - Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney
      damage. However, the prevalence and determinants of hyperoxaluria in chronic
      pancreatitis patients as well as its association with renal function decline have
      not been investigated.We performed an observational study. Urine oxalate to
      creatinine ratio was assessed on 2 independent random urine samples in
      consecutive adult patients with chronic pancreatitis followed at the outpatient
      clinic from March 1 to October 31, 2012. Baseline characteristics and annual
      estimated glomerular filtration rate (eGFR) change during follow-up were compared
      between patients with hyper- and normo-oxaluria.A total of 48 patients with
      chronic pancreatitis were included. The etiology of the disease was toxic (52%),
      idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%).
      Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found
      in 23% of patients. Multivariate regression analysis identified clinical
      steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent
      predictors of hyperoxaluria. Taken together, a combination of clinical
      steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a
      positive predictive value of 100% for hyperoxaluria. On the contrary, none of the
      patients with a fecal elastase-1 level >100 MUg/g had hyperoxaluria. Longitudinal
      evolution of eGFR was available in 71% of the patients, with a mean follow-up of
      904 days. After adjustment for established determinants of renal function decline
      (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine
      oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR
      decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis
      and associated with faster decline in renal function. A high urine oxalate to
      creatinine ratio in patients with chronic pancreatitis is best predicted by
      clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further
      studies will need to investigate the mechanisms of renal damage in chronic
      pancreatitis and the potential benefits of therapies reducing oxaluria.

PMID- 28489753
TI  - Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer
      after gemcitabine-based chemotherapy failure.
AB  - BACKGROUND: This study aimed to determine the maximum tolerated dose (MTD), dose
      limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after
      gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer
      (MPC). METHODS: We studied 18 histopathologically proven MPC patients. The
      schedule was 85 mg/m oxaliplatin, irinotecan, and 400 mg/m leucovorin, followed
      by 400 mg/m 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m 5-FU as a 46
      hour continuous infusion biweekly. The dose of irinotecan was defined as follows:
      level 0: 100 mg/m, level 1: 125 mg/m, level 2: 150 mg/m, and level 3: 180 mg/m.
      The doses of other drugs were fixed. The primary endpoint of phase II study was
      the response rate (RR). RESULTS: We initially evaluated 6 patients in a phase I
      study. One patient developed neutropenia and 1 patient developed hyperglycemia
      and severe infection. Accordingly, level 1 was chosen as the MTD. According to a
      phase II study, the RR was 22.2% and the disease control rate was 61.1%. The
      progression-free survival and overall survival were 2.8 (range, 0.7-19.1) and 9.8
      (2.4-19.8) months, respectively. The most common severe adverse event was
      neutropenia (66.7%). Febrile neutropenia occurred in 1 (5.6%) case. CONCLUSION:
      The recommended dose was 85 mg/m oxaliplatin, 100 mg/m irinotecan, and 400 mg/m
      leucovorin, followed by 400 mg/m 5-FU as a bolus on day 1 and 2400 mg/m 5-FU as a
      46-hour continuous infusion. These results indicate that second-line FOLFIRINOX
      is a marginally effective treatment for GEM-based chemotherapy failure cases.

PMID- 28489754
TI  - Relationship between SRD5A2 rs9282858 polymorphism and the susceptibility of
      prostate cancer: A meta-analysis based on 20 publications.
AB  - The pathogenetic mechanism of prostate cancer (PCa) has not been understood
      completely, and gene polymorphisms have been demonstrated to play a critical role
      in the course. It has been reported that rs9282858 polymorphism of steroid 5
      alpha-reductase type 2 (SRD5A2) may affect the susceptibility of PCa, but some
      researches showed different results. We therefore carried out a meta-analysis to
      clarify this relationship.Relevant studies were identified through PubMed and
      Chinese National Knowledge Infrastructure databases concerning the association
      between SRD5A2 rs9282858 polymorphism and PCa. Odds ratios (ORs) with their 95%
      confidence intervals (95% CIs) were calculated to assess the strength of the
      association. Additionally, stratified analyses were performed based on ethnicity
      and source of control. Besides, heterogeneity test, sensitivity analysis, and
      publication bias evaluation were conducted in current meta-analysis as
      well.Ultimately, 20 publications incorporating 30 case-control studies were
      included in this meta-analysis, involving a total of 7300 cases and 7952
      controls. The overall results demonstrated that SRD5A2 rs9282858 polymorphism was
      remarkably associated with increased susceptibility of PCa (TT vs. AA: OR = 4.08,
      95% CI = 1.94-8.58; TT + AT vs. AA: OR = 1.28, 95% CI = 1.11-1.47; TT vs. AA +
      AT: OR = 4.44, 95% CI = 2.12-9.27; allele T vs. allele A: OR = 1.34, 95% CI =
      1.17-1.54). After subgroup analyses by ethnicity and source of control, we also
      observed a similar trend in Latinos, other-ethnicity, population-based, and
      hospital-based groups under corresponding genetic models.Our findings indicate
      that SRD5A2 rs9282858 polymorphism may be a susceptible factor to PCa.

PMID- 28489755
TI  - Kennedy disease with difficulty in differential diagnosis: A case report.
AB  - RATIONALE: Kennedy disease (KD) is also known as spinal bulbar muscular
      dystrophy. As KD has similar symptoms with most neuromuscular diseases, so it is
      difficult to make a rapid diagnosis clinically. PATIENT CONCERNS: We report a
      case of a 43-year-old male with progressive limb proximal weakness without family
      history. Physical examination showed gynecomastia, erectile dysfunction,
      bilateral tendon reflex and quadriceps weakness, and tongue muscle atrophy.
      DIAGNOSES: Laboratory examination found increased creatine kinase, impaired
      glucose tolerance, and abnormal lactic acid values. There was no mutation or copy
      number variant in SMN1 gene and related mitochondrion genes tested, even with the
      use of multiplex ligation probe- dependent amplification technique. Diagnosis was
      confirmed with genetic analysis which displayed trinucleotide CAG (glutamine)-
      repeat expansion in the androgen-receptor gene. INTERVENTIONS AND OUTCOMES: The
      patient achieved good prognosis with symptomatic treatment after diagnosis.
      LESSONS: To diagnose KD, clinicians should pay more attention to differentiate KD
      and myasthenia gravis, mitochondrial myopathy, and amyotrophic lateral sclerosis.
      Gene analysis was the key in detecting this rare confusing disease in the
      patient.

PMID- 28489757
TI  - Ultrasound-guided catheterization of the left subclavian vein without recognition
      of persistent left superior vena cava: A case report.
AB  - RATIONALE: A persistent left superior vena cava (PLSVC) is rare, but the most
      common thoracic venous anomaly. We report a case of PLSVC unrecognized during
      left subclavian vein catheterization using real-time ultrasound-guided
      supraclavicular approach. PATIENT CONCERNS: A 79-year-old man with history of
      hypertension presented with traumatic subdural hemorrhage, subarachnoid
      hemorrhage, and epidural hemorrhage. Before the operation, a central venous
      catheter (CVC) was placed into the left subclavian vein. DIAGNOSES: A dilated
      coronary sinus on echocardiogram and subsequent agitated saline test confirmed
      the diagnosis of PLSVC. INTERVENTIONS: A CVC was placed into the left subclavian
      vein under real-time ultrasound guide, with supraclavicular approach. A
      postoperative chest X-ray revealed a left-sided paramediastinal course of the
      CVC; the CVC was removed under the impression of malposition. OUTCOMES: The CVC
      functioned properly. LESSONS: Ultrasound is used for safe and correct placement
      of CVC; however, the presence of PLSVC could not be detected by ultrasonography
      in this case. When the chest radiograph shows the central venous catheter passing
      along the border of the left heart and a dilated coronary sinus detected on
      echocardiogram, we should have suspicion of a PLSVC.

PMID- 28489756
TI  - The genetic association between polymorphisms in lymphotoxin-alpha gene and
      ankylosing spondylitis susceptibility in Chinese group: A case-control study.
AB  - The study was designed to reveal the genetic relationship of lymphotoxin-alpha
      (LTA) polymorphisms with risk of ankylosing spondylitis (AS) in Chinese Han
      population.LTA polymorphisms were genotyped by polymerase chain reaction-direct
      sequencing (PCR-DS) in 138 AS patients and 141 healthy controls. The genotype
      distribution in control group was checked the status of Hardy-Weinberg
      equilibrium (HWE). Odds ratio (OR) with 95% confidence interval (95%CI)
      calculated by chi test was used to show effects of LTA polymorphisms on AS risk.
      Logistic regressive analysis was used to calculate the adjusted OR values.
      Additionally, the linkage disequilibrium of LTA polymorphisms was examined by
      Haploview.G allele of rs909253 was significantly higher frequency in AS patients
      (P = .02), which was associated with the increased risk of AS (OR = 1.53, 95%CI =
      1.07-2.18). The carriages of GG genotype in rs909253 showed a high risk of AS
      occurrence, compared with AA genotype carriers (OR = 2.46, 95%CI = 1.13-5.35).
      Multivariate analysis demonstrated that the G allele (OR = 1.52, 95%CI = 1.05
      2.15) and GG genotype (OR = 2.36, 95%CI = 1.06-5.24) of rs909253 were still
      positively associated with AS susceptibility. However, there was no significant
      association between AS risk and rs2239704 or rs2229094.LTA rs909253 polymorphism
      contributes to the occurrence of AS.

PMID- 28489759
TI  - Shen-Cao granules formulated based on traditional Chinese medicine alleviates
      bone marrow suppression caused by platinum-based anticancer reagents.
AB  - BACKGROUND: The aim of this study was to evaluate effects of Shen-Cao granules
      for the prevention of thrombocytopenia caused by anticancer chemotherapy.
      METHODS: In this prospective study, a total of 200 patients with various
      malignant tumors were enrolled and evenly divided into a Shen-Cao granule
      treatment (n = 100) and a control group (n = 100). After 2 cycles chemotherapy
      with any combination of platinum-based drugs (cisplatin, carboplatin, and
      nedaplatin), the blood platelet (PLT) counts, levels of the PLT production
      regulator thrombopoietin (TPO), PLT aggregation rates, and the PLT activation
      marker CD62P expressions were monitored for 2 weeks. RESULTS: During 2 weeks of
      post-chemotherapy, the mean values of the minimum PLT count were 49.65 +/- 7.35 *
      10/L in the treatment group and 31.56 +/- 9.32 * 10/L in the control group. The
      PLT count in the treatment group reached the lowest value 1.8 days later and
      recovered to a concentration >=100 * 10/L 3 days earlier than in the control
      group. The concentrations of the TPO were 71.43 +/- 1.74 and 87.24 +/- 0.92 ng/mL
      in the treatment group and 65.75 +/- 1.39 and 67.75 +/- 0.67 ng/mL in the control
      group at 7 and 14 days post-chemotherapy, respectively. The maximum PLT
      aggregation rate declined after chemotherapy in the treatment group from 58.14 +/
      11.46% to 52.89 +/- 10.52%, while it increased in the control group from 56.94
      +/- 10.55% to 61.75 +/- 12.26%. Coordinately, the expression of CD62P in the
      treatment group decreased from 6.17 +/- 0.59% to 4.89 +/- 0.72%, while it
      increased from 6.09 +/- 0.75% to 7.75 +/- 0.67% in the control group. CONCLUSION:
      Our study demonstrated that Shen-Cao granule treatment alleviated
      thrombocytopenia after chemotherapy, and reduced tumor-induced PLT activation and
      aggregation.

PMID- 28489758
TI  - Analysis of radioiodine therapy and prognostic factors of differentiated thyroid
      cancer patients with pulmonary metastasis: An 8-year retrospective study.
AB  - To assess the efficacy of radioiodine therapy (RIT) and investigate the
      prognostic factors for patients with pulmonary metastasis secondary to
      differentiated thyroid carcinoma (DTC) through a retrospective study. A total of
      80 patients with radioactive iodine-131 (I)-avid pulmonary metastasis from DTC
      treated with I from 2007 to 2014 at our institution entered the study. Treatment
      response was mainly measured by two parameters: serum thyroglobulin (Tg) levels
      and post-therapeutic I whole-body scan (WBS). Treatment variables were assessed
      for statistical significance using the univariate and multivariate analyses. A
      receiver-operating characteristic (ROC) curve was also plotted to verify the
      accuracy of predictors. Of these 80 patients, the overall effective rate was
      72.5% (58/80), the rates for complete response (CR), partial response (PR), and
      no response (NR) were 20.0%, 52.5%, and 27.5%, respectively. Univariate analysis
      showed that gender, pulmonary nodule size, absence or presence of extrapulmonary
      distant metastases, age, and Tg level at diagnosis were significantly associated
      with I therapy efficacy. Binary logistic regression analysis revealed that older
      patients (odds ratio [OR]:1.481, 95% confidence interval [CI]: 1.457-2.091, P =
      .020), subjects with higher Tg levels at diagnosis (OR: 1.046, 95% CI: 1.016
      1.119, P = .014), and those with extrapulmonary distant metastases (OR: 1.185,
      95%CI: 1.025-1.463, P = .020) had a higher probability of poor prognosis. The
      optimal cutoffs for age and Tg level to predict I therapy efficacy for DTC with
      lung metastases were 46 years old and 55.50 ng/mL, respectively, based on ROC
      analysis. This study indicated that most DTC patients with pulmonary metastases
      can obtain partial or complete remission after RIT, while older patients with
      higher Tg levels at diagnosis and extrapulmonary distant metastases more likely
      show poor prognosis.

PMID- 28489760
TI  - Chronic obstructive pulmonary disease is independently associated with
      hypertension in men: A survey design analysis using nationwide survey data.
AB  - Although studies have shown that chronic obstructive pulmonary disease (COPD) and
      hypertension are linked as comorbidities, it remains unclear whether COPD is
      independently associated with the risk of hypertension or is caused by common
      risk factors such as age and smoking. The objective of this study was to
      investigate the relationship between COPD and hypertension by using nationally
      representative data.This cross-sectional study analyzed data from the Korea
      National Health and Nutrition Examination Survey V conducted during 2010 to 2012.
      Hypertension was defined as a mean systolic blood pressure >= 140 mm Hg and/or a
      diastolic blood pressure >= 90 mm Hg, or current consumption of antihypertensive
      medications. A diagnosis of COPD was defined as a smoking history of at least 10
      pack-years with airflow limitation on spirometry. Multivariate logistic
      regression was performed to investigate the independent association between COPD
      and hypertension after adjusting for covariates. Survey design analyses were
      conducted for all analyses.Among 4043 men (aged >= 40 years) who underwent
      spirometry, 2190 (54.2%) had hypertension. Even after adjusting for age, body
      mass index, smoking status, diabetes, metabolic syndrome, and stroke, COPD was
      independently associated with hypertension (adjusted odds ratio, 1.71; 95%
      confidence interval, 1.37-2.13; P < .001). Adjusted pulse pressure significantly
      increased as the ratio of forced expiratory volume in 1 s (FEV1) to forced vital
      capacity and FEV1 decreased.COPD is independently associated with hypertension,
      and this could explain the link between the risk of cardiovascular diseases and
      COPD.

PMID- 28489761
TI  - Quality of life in adolescent patients with idiopathic scoliosis after brace
      treatment: A meta-analysis.
AB  - BACKGROUND: Whether brace-treated adolescents with idiopathic scoliosis (AIS)
      have improved quality of life (QoL) is still unknown. Thus, we conducted a meta
      analysis to compare the QoL of brace-treated AIS patients with untreated AIS
      patients. The pain, self-image/appearance, mental health, function/activity,
      satisfaction with management, total score without satisfaction, and total score
      of patients were used to measure the QoL after the intervention. METHODS:
      Multiple electronic databases including PubMed, Web of Science, and Embase were
      searched for all years up to June 30, 2016. Articles in English that used the
      Scoliosis Research Society-22 (SRS-22) or a modified version of the SRS-22
      questionnaire to evaluate the QoL differences between brace-treated AIS patients
      and untreated AIS patients were included in the meta-analysis. The Newcastle
      Ottawa Scale was used in the quality of literature evaluation. The pooled
      standardized mean difference (SMD) with its corresponding 95% confidence interval
      (CI) for each parameter was computed. Egger test and Begg test were used to test
      for publication bias. RESULTS: The SRS-22 or a modified SRS-22 questionnaire was
      used to evaluate the QoL after surgery. There was no significant difference in
      pain (SMD = 0.123, 95% CI: -0.101 to 0.347, P = .282), self-image/appearance (SMD
      = 0.108, 95% CI: -0.116 to 0.332, P = .334), mental health (SMD = 0.031, 95% CI: 
      0.130 to 0.201, P = .365), function/activity (SMD = 0.202, 95% CI: -0.022 to
      0.425, P = .077), and total score without satisfaction (SMD = 0.123, 95% CI: 
      0.232 to 0.478, P = .497) between the untreated (observation) and brace-treated
      AIS patients, whereas a significant difference was observed in satisfaction with
      management (SMD = 0.393, 95% CI: 0.127-0.659, P = .004) and total score (SMD =
      0.312, 95% CI: 0.054-0.571, P = .018) between the 2 groups. CONCLUSION: Our meta
      analysis indicated that brace-treated AIS patients had a higher QoL. However,
      further analysis could not be performed because of insufficient data, such that
      we were unable to make subgroup analysis of QoL for different types of AIS and
      the therapeutic methods chosen by brace-treated AIS patients.

PMID- 28489762
TI  - Comparison of local infiltration analgesia and sciatic nerve block as an adjunct
      to femoral nerve block for pain control after total knee arthroplasty: A
      systematic review and meta-analysis.
AB  - BACKGROUND: To perform a meta-analysis to assess the efficiency and safety
      between local infiltration analgesia (LIA) and sciatic nerve block (SNB) when
      combined with femoral nerve block (FNB) for pain control following total knee
      arthroplasty (TKA). METHODS: We systemically searched the following electronic
      databases for potentially relevant articles: Embase (1980-2017.01), Medline (1966
      2017.01), PubMed (1966-2017.01), ScienceDirect (1985-2017.01), web of science
      (1950-2017.01) and the Cochrane Library. Only studies published in English that
      were accessible online were considered. Furthermore, we only considered studies
      that were published from 1966 to 2017. Only studies that met the following
      inclusion criteria were considered: (a) patients were adult human subjects who
      were set to undergo TKA; (b) the intervention was either SNB combined with FNB or
      LIA combined with FNB; (c) the outcomes of the studies, such as visual analog
      scale (VAS) scores, morphine consumption, length of stay and postoperative
      adverse effects, including the risk of nausea, vomiting and falls, were reported;
      (d) studies were either RCTs or non-RCT. Meta-analysis was performed using Stata
      11.0 software. Modified Jadad score (7-points scale) which was based on Cochrane
      Handbook for Systematic Reviews of Interventions is used for assessment of RCTs.
      The Methodological Index for Nonrandomized Studies (MINORS) scale was used to
      assess non-RCTs with scores ranging 0 to 24. The synthesis of the outcomes for
      all studies was calculated as the weighted average rate by using a fixed or
      random effect model which depends on statistical heterogeneity. Systematic review
      registration number is CRD42017110661. RESULTS: Three randomized controlled
      trials (RCTs) and 2 nonrandomized controlled trials (Non-RCTs), including 240
      patients met the inclusion criteria. The present meta-analysis indicated that
      there were significant differences between groups in terms of visual analog scale
      (VAS) score at 12 hours (SMD = -0.337, 95% CI: -0.593 to -0.081, P =.010), VAS
      score at 24 hours (SMD = -0.337, 95% CI: -0.612 to -0.061, P =.017), morphine
      equivalent consumption at 24 hours (SMD = -0.371, 95% CI: -0.627 to -0.114, P =
      .005) and incidence of nausea (RD = 0.215, 95% CI: 0.078 to 0.353, P = .002) and
      vomiting (RD = 0.143, 95% CI: 0.026 to 0.260, P = .017). CONCLUSION: FNB combined
      with SNB provided decreased VAS scores and less morphine consumption at 12 and 24
      hours compared with FNB combined with LIA in total knee arthroplasty. In
      addition, it was associated with lower risks of nausea and vomiting. We assessed
      the quality of the evidence as low to very low; therefore, our confidence in the
      effect estimate is limited, and the true effect may be substantially different
      from our estimates. Further studies should focus on surgeries that are known to
      be associated with significant postoperative pain, particularly surgeries where
      improved pain control may deliver significant clinical benefits through reduced
      morbidity, or cost-effectiveness benefits through faster rehabilitation and
      discharge. The present meta-analysis has the following limitations: (1) only 5
      studies were included in the meta-analysis. Although all of them are recently
      published studies, the sample sizes are relatively small; (2) Functional outcome
      is an important parameter; however, owing to the insufficiency of relevant data,
      we failed to perform a meta-analysis on functional outcome; (3) The doses of
      anesthetics and the concomitant pain management regimes varied between the
      studies, which may have influenced the results; (4) The duration of follow-up was
      relatively short, which might have led to an underestimating of complications;
      and (5) publication bias present in the meta-analysis may have influenced the
      results.

PMID- 28489763
TI  - Naturally occurring drug resistance associated variants to hepatitis C virus
      direct-acting antiviral agents in treatment-naive HCV genotype 1b-infected
      patients in China.
AB  - The direct-acting antiviral agents (DAAs) have drastically improved the prognosis
      of hepatitis C virus (HCV) patients. However, the resistance-associated variants
      (RAVs) to DAAs may hamper treatment. There was a lack of data on the prevalence
      of pre-exist RAVs in Chinese HCV-infected patients. We performed nested PCR
      assays on 74 HCV genotype 1b-infected patients to amplify HCV viral regions of
      NS3, NS5A, and NS5B to investigate the prevalence of RAVs to DAAs in treatment
      naive HCV genotype1b-infected patients in China. The mutations A156S, T54S, and
      D168Y of the NS3/4A region were found in 18.33% (11/60), 6.67% (4/60), and 1.67%
      (1/60) of the successfully amplified cases. Mutations Q30R, L31M, and H58P of the
      NS5A region were confirmed in 57.63% (34/59), 1.69%(1/59), and 86.44% (51/59) of
      the cases. Mutations C316N, S365A, M414L, M423I, Y448H, I482T, I482 V, V494L,
      P495S, and V499A of the NS5B region were detected in 100% (60/60), 3.33% (2/60),
      5.88% (3/51), 1.96% (1/51), 1.96% (1/51), 5.88% (3/51), 1.96% (1/51), 3.92%
      (2/51), 5.88% (3/51), and 15.69% (8/51) of cases, respectively. Naturally
      occurring RAVs to DAAs pre-exist in treatment-naive Chinese HCV genotype 1b
      infected patients and the characteristic is different from that in Europe and the
      United States. Clinicians should consider RAVs upon the introduction of DAA-based
      antiviral therapy.

PMID- 28489764
TI  - Mutual associations between intellectual disability and epilepsy-related
      psychiatry disability: Population-based study.
AB  - Epilepsy is the third-leading cause of psychiatry disability in China, and
      intellectual disability (ID) is also 1 major type of disabilities in China. This
      study estimates the prevalence of comorbidities with ID and epilepsy-related
      psychiatry disability (EPD) and examines mutual associations within ID and
      EPD.Data were taken from the Second China National Sample Survey on Disability,
      which was a nationally representative, population-based survey. To derive a
      nationally representative sample, the survey used multistage, stratified, cluster
      random sampling with probability proportional to size. The disabled people who
      had ID and EPD based on the World Health Organization International
      Classification of Functioning, Disability, and Health and the International
      Statistical Classification of Diseases. The cox-proportional hazards model was
      used to examine the associations between ID and EPD considering the happened
      sequence of ID and EPD.The prevalence of ID with EPD was 0.14 (95% confidence
      interval: 0.09-0.19) per 1000 people. Age was strongly associated with the risk
      of EPD, which was diagnosed after ID, especially among young ID population.
      Except for age, other variables were also associated between ID and EPD
      considering sequence of ID and EPD.This study is the first national study to
      explore mutual associations with ID and EPD and highlights the young ID children
      with high risk of development of epilepsy. To address the challenge of ID with
      EPD disability in China, the government should adjust its strategies for
      healthcare systems to prevent disability.

PMID- 28489765
TI  - Anesthetic management of cesarean delivery in parturients with ruptured sinus of
      Valsalva aneurysm: CARE-compliant 2 case reports and literature review.
AB  - RATIONALE: Ruptured sinus of Valsalva aneurysm is rare and dangerous in
      parturients. Few cases of ruptured SVA in pregnancy are reported, and the
      anesthetic management for cesarean delivery has scarcely been described. PATIENT
      CONCERNS: A parturient at 37-week gestation complained of a sore throat and cough
      that started 3 days before admission, followed 1 day later by fever, dizziness,
      breathlessness, and palpitation on exertion. Case two at 36-week gestation
      complained of a 1-day history of bloating in the lower abdomen. DIAGNOSES: Full
      term and preterm parturients with ruptured sinus of Valsalva aneurysm.
      INTERVENTIONS: Cesarean deliveries were performed with incremental epidural
      anesthesia technique under invasive monitoring. Surgical correction of the
      ruptured sinus of Valsalva aneurysms and ventricular septal defect were performed
      uneventfully 13 days and 7 days postpartum, respectively, for the 2 cases.
      OUTCOMES: No complications were observed in the intra- or postoperative period
      for both mothers and babies. LESSONS: We reviewed the pertinent literature and
      reached the following conclusions: use of a multidisciplinary team to guide
      anesthetic management is helpful and necessary; and both general anesthesia and
      incremental epidural anesthesia can be safely used in parturients with ruptured
      sinus of Valsalva aneurysm.

PMID- 28489766
TI  - Sex difference determined the role of sex hormone-binding globulin in obese
      children during short-term weight reduction program.
AB  - The relationship between hyperinsulinemia and decreased sex hormone-binding
      globulin (SHBG) levels has been observed in obese adults and children. Weight
      reduction not only increased insulin sensitivity but also elevated serum SHBG
      levels in obese adults and children. However, the correlation between the changes
      in insulin resistance indices and serum SHBG concentration during weight
      reduction program (WRP) is not fully understood, particularly in obese children.
      This study is to evaluate whether SHBG level is a potential biomarker that can be
      used to assess insulin resistance in obese children during a short-term WRP.
      Forty-eight obese Taiwanese children (11.7 +/- 2.2 years; 25 boys and 23 girls)
      participating in 8-week WRP were studied. Anthropometric measurements, lipid
      profiles, insulin resistance indices, and serum SHBG concentration were recorded
      at baseline and at the end of the WRP. The results showed body weight (BW), body
      mass index (BMI), body fat percentage (BF%), body fat weight (BFW), and insulin
      resistance indices such as fasting insulin, fasting insulin to glucose ratio,
      homeostasis model assessment (HOMA) of insulin resistance, log (HOMA) all
      significantly decreased after the 8-week WRP. With respect to lipid profiles,
      only high-density lipoprotein cholesterol (HDL-C) levels increased in both sexes.
      At baseline, insulin resistance indices were inversely correlated with SHBG
      concentrations in girls, but not in boys. The difference in SHBG after WRP was
      2.58 nmol/L (95% confidence interval [CI]: -3.51, 8.66) in boys and 0.58 nmol/L
      (95% CI: -5.23, 6.39) in girls. There was a trend toward increased serum SHBG
      levels in boys (P = .39) and girls (P = .84) after weight loss, but a
      significantly negative correlation between the change in SHBG and in each of the
      insulin resistance indices only in the girls after adjusting age and DeltaBFW
      during WRP.In conclusion, short-term WRP has the potential effects of decreased
      BW, BMI, BF%, and BFW, as well as increased serum HDL-C levels and insulin
      sensitivity in obese Taiwanese children. Although serum SHBG levels moderately
      increased in both sexes during short-term WRP, measuring the change in SHBG
      concentrations might be a potential biomarker to evaluate improvement in insulin
      resistance in girls only, and not in boys.

PMID- 28489768
TI  - Prevalence of comorbidities in chronic obstructive pulmonary disease patients: A
      meta-analysis.
AB  - BACKGROUND: This study compares the prevalence rates of comorbidities between
      chronic obstructive pulmonary disease (COPD) and non-COPD control patients
      reported in literature. METHOD: Literature was searched in several electronic
      databases. After the selection of studies by following precised eligibility
      criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and
      sensitivity analyses under random effects model. RESULTS: Eleven studies
      (47,695,183 COPD and 47,924,876 non-COPD control patients' data) were used for
      meta-analysis. Average age of COPD patients was 66.66 +/- 8.72 years of whom 55.4
      +/- 11.9% were males. The prevalence of cardiovascular comorbidities [OR 1.90,
      95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular
      comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95%
      CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P =
      .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P <
      .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001),
      musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD
      respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR
      1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients
      than in non-COPD controls. CONCLUSION: COPD is associated with significantly
      higher comorbidities than in other diseases that should be taken into
      consideration in COPD control strategies.

PMID- 28489767
TI  - The association between hepatitis B mutants and hepatocellular carcinoma: A meta
      analysis.
AB  - BACKGROUND: More and more studies focus on the relationship between hepatitis B
      virus (HBV) basal core promoter/precore (BCP/PC) mutations, but it remains
      controvercial, we conducted a meta-analysis to investigate the features of
      hepatitis B virus basal core promoter/precore mutations on the progression of
      hepatocellular carcinoma (HCC). METHODS: A comprehensive search was conducted for
      articles published between January 1, 2005 and December 31, 2015 using the
      following databases: PubMed, Embase, Cochrane Library, Wanfang, and China
      National Knowledge Infrastructure. Medical subject heading terms were prioritized
      in setting the search strategy. Search terms included ("hepatitis B virus"),
      ("mutation or mutations or mutant"), and ("hepatocellular carcinoma" or "liver
      cancer" or hepatoma). A meta-analysis of pooled results from case-control studies
      examined the association between mutations G1896A, A1762T, G1764A, and
      A1762T/G1764A and the risk of HCC. RESULTS: We included 29 articles for analysis
      and found that G1896A (summary odds ratios [OR] = 2.04, 95% confidence interval
      [CI] = 1.41-2.95), A1762T (summary OR = 3.96, 95% CI = 1.98-7.92), G1764A
      (summary OR = 3.48, 95% CI = 1.99-6.09), and A1762T/G1764A (summary OR = 3.96,
      95% CI = 2.77-5.65) are each associated with a statistically significant increase
      in the risk of HCC. CONCLUSION: In summary, we found that G1896A, A1762T, G1764A,
      and A1762T/G1764A are associated with an increased risk of HCC.

PMID- 28489769
TI  - Retroperitoneal metastatic poorly differentiated carcinoma with beta-human
      chorionic gonadotropin secretion presenting as a psoas abscess: A case report and
      review of the literature.
AB  - RATIONALE: Psoas abscesses generally arise from a contiguous intra-abdominal or
      pelvic infectious process or hematogenous spreading of bacteria. The serum beta
      human chorionic gonadotropin has been used to detect normal or ectopic pregnancy.
      It also can be utilized in following up carcinomas. PATIENT CONCERNS: Here, we
      reported a case of a 47-year-old woman who presented with a left psoas mass
      presumptively diagnosed as an abscess secondary to lumbar tuberculosis In
      addition, the patient had abnormal increase of beta-human chorionic gonadotropin.
      The computed tomography (CT) scan and magnetic resonance imaging (MRI) showed
      that the 5th lumbar vertebral infection or tuberculosis with left psoas abscess.
      CT-guided percutaneous biopsy, surgical exploration and biopsy, and F-FDG
      (fluorodeoxyglucose) positron emission tomography-CT (PET-CT) were used to make a
      definite diagnosis. The sigmoidoscopy and biopsy were used to further diagnose.
      DIAGNOSES: The biopsy of left psoas demonstrated metastatic or infiltrating
      poorly differentiated carcinoma with secretion of beta-human chorionic
      gonadotropin. The subsequent pathological examination of neoplasm showed the same
      pathologic morphology. INTERVENTIONS: Appropriate treatment of infected
      retroperitoneal mass, systematic chemotherapy and cancer biotherapy for
      metastatic poorly differentiated carcinoma were taken. OUTCOMES: Interventions
      provided little help until the patient died of secondary infection and multiple
      organ failure. LESSONS: This case represents an extremely unusual clinical
      presentation of metastatic poorly differentiated carcinoma with secretion of beta
      human chorionic gonadotropin presenting as a psoas abscess. Physicians also need
      to sharpen their awareness of the potential malignant carcinomas mimicking psoas
      abscess.

PMID- 28489770
TI  - Degeneration of corticofugal fibers in a patient with primary progressive
      freezing gait: A case report.
AB  - RATIONALE: To report a patient with primary progressive freezing gait (PPFG)
      whose degeneration of corticofugal tract (CFT) from the supplementary motor area
      (SMA) was demonstrated using diffusion tensor tractography (DTT). PATIENT
      CONCERNS: A 66-year-old woman presented with a solitary symptom of a sudden
      transient break on walking (i.e., freezing gait), which slowly progressed for 4
      years. DIAGNOSES: Imaging evidence using magnetic resonance imaging and F
      florinated-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-lodophenyl)
      nortropane positron emission tomography scanning was unremarkable, and our
      patient's symptom was not affected by dopamine agonist medication. Based on the
      clinical symptoms and imaging findings, we diagnosed our patient as having PPFG.
      INTERVENTIONS: From the patient and 20 age- and sex- matched normal controls,
      diffusion tensor imaging data were acquired using a 1.5 T magnetic resonance
      scanner. OUTCOMES: In DTT findings, the CFT from the left SMA was partially torn
      and thinned. Moreover, the fractional anisotropy value and tract volume of CFT
      from the left SMA were more than two standard deviations lower than those of
      normal controls. LESSONS: In our opinion, the lesion in the CFT from the left SMA
      in our patient was attributed to the occurrence of PPFG. We believe that the
      results of this study suggest one of the pathological mechanisms for the
      occurrence of gait difficulty in PPFG.

PMID- 28489771
TI  - Chronic active Epstein-Barr virus infection associated with hemophagocytic
      syndrome and extra-nodal natural killer/T-cell lymphoma in an 18-year-old girl: A
      case report.
AB  - RATIONALE: Chronic active Epstein-Barr virus infection (CAEBV) associated with
      hemophagocytic syndrome (HPS) and extra-nodal natural killer (NK)/T-cell lymphoma
      (ENKL) is a rare life-threatening disorder. This disease is easily misdiagnosed
      because of its varied presentations. PATIENT CONCERNS: An 18-year-old girl was
      admitted to our hospital with a history of edema in the lower limbs and
      intermittent fever lasting for more than 1 month. At admission, she had severe
      liver injury of unknown etiology. Laboratory test results revealed pancytopenia,
      hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. Results of
      serologic tests for EBV were positive. Results of a skin biopsy indicated EBV
      positive NK/T-cell lymphoma, and bone marrow aspiration revealed focal
      hemophagocytosis and atypical lymphoid cells. DIAGNOSIS: On the basis of these
      findings, we diagnosed the case as extra-nodal NK/T-cell lymphoma-associated HPS
      (natural killer/T-cell lymphoma-associated hemophagocytic syndrome), which is
      commonly induced by CAEBV. INTERVENTIONS: Treatment consisted of general
      management of hepatitis, supplemented with albumin and empirical antibiotic
      therapy. OUTCOMES: The patient died from massive gastrointestinal hemorrhage a
      week after she was discharged from the hospital. LESSONS: ENKL and HPS present
      with varied features and are generally fatal; therefore, clinicians should
      proceed with caution in suspected cases. HPS should be considered when the
      patient presents with fever, hepatosplenomegaly, pancytopenia, and liver failure.
      When HPS is suspected, clinicians should determine the underlying cause, such as
      severe infection, including infection with viruses such as EBV; genetic
      predisposition; or underlying malignancies, especially lymphoma because of its
      strong association with HPS.

PMID- 28489772
TI  - Primary diffuse large B cell lymphoma of the uterine cervix successfully treated
      by combined chemotherapy alone: A case report.
AB  - RATIONALE: Primary lymphomas of the uterine cervix are a rare disease. They are
      often misdiagnosed because of their rarity and because they can be easily
      confused with a squamous cell carcinoma of the cervix, as they are usually
      presented as exophytic mass with vaginal bleeding as their most common symptoms.
      Nevertheless, considering that both the prognosis and the treatment are
      completely different between them, differential diagnosis should be taken into
      account. PATIENT CONCERNS: A case of a 51-year-old woman with a primary diffuse
      large B-cell lymphoma of the cervix is presented. DIAGNOSES: Diagnosis of this
      tumor was a challenge for pathologists and clinicians, as four biopsies were
      needed to achieve a final diagnosis. INTERVENTIONS: Patient was successfully
      treated with combined Rituximab and chemotherapy (R-CHOP) alone. OUTCOMES:
      Complete remission, confirmed through biopsy, was reached after six courses of
      chemotherapy. At 2-years follow up, patient is alive and free of disease.
      LESSONS: Considering that the prognosis and treatment of primary malignant
      lymphoma of the cervix are completely different than that of the squamous cell
      carcinoma, awareness of this disease should be considered in the differential
      diagnosis.

PMID- 28489773
TI  - CT analysis of anatomical variation and injury affecting posterior pedicle screw
      fixation for unstable Hangman fractures.
AB  - The aim of this study was to evaluate the anatomical variations and injuries in
      patients with unstable Hangman fractures that affected the posterior pedicle
      screw placement of C2 to C3 and retrospectively review our experience with
      management of these fractures. Clinical data were reviewed in 72 patients with
      unstable Hangman fractures, especially using 3-dimensional computed tomography
      (3D-CT) scan to identify the presence of anatomical variations or injuries and
      analyzing the treatment strategies we used. Twenty-two patients (22/72, 30.6%)
      with 39 (C2 or C3) risk factors were not fit for safe C2 to C3 pedicle screw
      placement, due to factors such as small pedicle size of C2 or C3, high-riding
      vertebral arteries, fractured fragments encased into vertebral canal, or
      transverse process foramen of C2, sclerotic pedicles and pedicle fractures of C3.
      One or more than one of these risk factors could pose more risks of arterial or
      neural structures damages to pedicle screw fixation for unstable Hangman
      fractures. Individualized treatment plans were made to minimize the risks of
      surgery for the 22 patients. There is a high incidence of anatomical variations
      and injuries in the C2 to C3 region in patients with unstable Hangman fractures
      that affect the pedicle screw placement. Preoperative evaluation of these
      conditions using 3D-CT scans is of paramount importance to avoid and decrease
      operative complications and to choose appropriate surgical techniques.

PMID- 28489774
TI  - Prognostic impact of C-reactive protein/albumin ratio on the overall survival of
      patients with advanced nonsmall cell lung cancers receiving palliative
      chemotherapy.
AB  - Recent studies have indicated that the C-reactive protein (CRP)/albumin (CRP/Alb)
      ratio is associated with clinical outcomes in patients with various carcinomas.
      However, no studies have explored the association between the ratio of CRP/Alb
      and clinical outcome of inoperable patients with nonsmall cell lung cancers
      (NSCLCs). We examined the prognostic impact of CRP/Alb ratio on 165 stage IV
      NSCLC receiving palliative chemotherapy. The optimal cutoff level of CRP/Alb
      ratio was set at 0.195. The median follow-up time was 9 months (range, 1-74
      months). On univariate analysis, high CRP/Alb ratio (>=0.195) was correlated (P <
      .001) with poorer overall survival (OS). Subgroup analysis of adenocarcinoma
      showed that CRP/Alb ratio was significantly (P < .001) associated with OS.
      Multivariate analysis showed that CRP/Alb ratio was an independent prognostic
      factor for OS (hazard ratio: 2.227, P = .001). Subgroup analysis revealed that
      the CRP/Alb ratio had a significant (P = .001) prognostic impact on
      adenocarcinoma patients receiving platinum chemotherapy. Elevated CRP/Alb ratio
      was significantly associated with male gender (P = .002) and smoking history (P =
      .009). The results of this study suggest that the CRP/Alb ratio might be used as
      a simple, inexpensive, and independent prognostic factor for OS of patients with
      advanced lung adenocarcinomas receiving platinum chemotherapy.

PMID- 28489775
TI  - Effects of nimodipine on postoperative delirium in elderly under general
      anesthesia: A prospective, randomized, controlled clinical trial.
AB  - Nimodipine is a clinical commonly used calcium antagonistscan lowering the
      apoptosis rate of hippocampal neuron to reduce the incidence of postoperative
      cognitive dysfunction (POCD). This study was designed to evaluate the effects of
      nimodipine on postoperative delirium in elderly under general anesthesia.Sixty
      patients shceduced spine surgery under general anesthesia were randomly assigned
      into 2 groups using a random number table: control group (Group C) and nimodipine
      group (Group N). In Group N, nimodipine 7.5 MUg/(kg * h) was injected continually
      30 minutes before anesthesia induction, while the equal volume of normal saline
      was given in Group C. At 0 minute before injection, 0 minute after tracheal
      intubation, 1 hour after skin incision and surgery completed (T1-4), blood
      samples were taken from the radial artery and jugular bulb for blood gas
      analysis. Cerebral oxygen metabolism-related indicators were calculated at the
      same time. Concentration of S100beta and glial fibrillary acidic protein (GFAP)
      were tested by ELISA. The incidence of postoperative delirium within 7 days after
      surgery was recorded.Cerebral oxygen metabolism-related indicators fluctuationed
      in the normal range in 2 groups at different time points and the difference were
      not statistically significant. Compared with Group C, S100beta and GFAP decreased
      and incidence of postoperative delirium reduced at T3-4 in Group N, the
      difference was statistically significant (P<.05).The present study suggests that
      nimodipine can reduce the development of postoperative delirium in elderly
      patients under general anesthesia, the reduction of brain injury and improvement
      of cerebral oxygen metabolism may be involved in the mechanism.

PMID- 28489776
TI  - Is C-reactive protein a marker of obstructive sleep apnea?: A meta-analysis.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common disease, distinguished by
      recurrent episodes of upper airway obstruction during sleep, with an inflammatory
      component. C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs
      CRP) are markers of systemic inflammation and may serve as biomarkers of OSA.
      METHODS: Scientific studies published from January 1, 2006, to January 1, 2016
      were obtained via searches of PubMed, Embase, SCI, and China National Knowledge
      Internet (CNKI) using relevant terms. Studies concerning serum CRP level/ hs-CRP
      in OSA patients were reviewed by 2 independent reviewers. Studies were included
      if they conform with our specific criteria of inclusion. Eligible studies were
      subjected to quality review, data extraction, and meta-analysis by using RevMan
      (version 5.2) and STATA (version 12.0). RESULTS: There were 15 studies that met
      inclusion criteria that included a total of 1297 subjects. Meta-analysis revealed
      that serum CRP levels in the OSA group were 1.98 mmol/L higher than those in
      control group (95% confidence interval: 1.39-2.58, P < .01). Similarly, serum hs
      CRP levels in the OSA group were 1.57 mmol/L higher than that in the control
      group (95% confidence interval: 0.96-2.18, P < .01). Subgroup analysis showed
      greater differences between OSA patients and controls in the setting of obesity
      (body mass index)> = 30. The total weighted mean difference (WMD) between OSA and
      controls within the subgroup of subjects who had a CRP was 2.10; for hs-CRP, the
      WMD was 2.49. Comparing OSA patients of mean apnea hypopnea index> = 15 and
      controls, the total WMD for the CRP subgroup was 2.19; for the hs-CRP subgroup,
      the WMD was 1.70. CONCLUSION: In our meta-analysis, serum CRP/hs-CRP levels were
      discovered to be higher in OSA patients compared with control subjects. Those
      with higher body mass index and apnea hyponea index demonstrated larger
      differences in CRP/hs-CRP levels. These data are consistent with an inflammatory
      component of OSA pathophysiology and support the role of CRP/hs-CRP as a
      biomarker in this disease.

PMID- 28489777
TI  - Affective temperament does not influence satisfaction after total knee
      arthroplasty.
AB  - BACKGROUND: Inherent temperament of the patient may predict the outcome of the
      surgical procedure. The purpose of this study was to ascertain whether negative
      affective temperament affects patient satisfaction and outcome measures. METHODS:
      This prospective study included 143 patients who underwent total knee
      arthroplasty for primary arthrosis. Preoperatively, the Memphis, Pisa, Paris and
      San Diego-Auto questionnaire was used to define the temperament of the patient.
      Knee Society Score (KSS) and short form-36 (SF-36) outcome measures were used to
      evaluate the functional outcome. RESULTS: No relationship was determined between
      temperament and satisfaction (P = .734). Overall, the satisfaction rate of the
      procedure in our patients was 93%. The KSS improved from a mean of 47.9 to 70.1
      (F = 124.275; P < .05) and the SF-36 physical component summary, and SF-36 mental
      component summary scores improved to a mean of 39.5 and 43.04 points,
      respectively. CONCLUSION: Temperament was not found to have any effect on patient
      satisfaction. However, patient satisfaction was directly related to better
      functional outcomes.

PMID- 28489779
TI  - Epidural hematoma after total hip arthroplasty in ankylosing spondylitis patient:
      A case report and review of the literature.
AB  - RATIONALE: Ankylosing spondylitis (AS) can affect the hip joint, causing
      deformity and disability. Total hip arthroplasty can obviously relieve the pain
      of the hip joint, and reconstruct the function of hip joint. Epidural anesthesia
      in this patient population has high risk of epidural hematoma, but the reason is
      unclear. PATIENT CONCERNS: A 44-year-old man diagnosed with AS underwent total
      hip arthroplasty. DIAGNOSES: Six days after operation, he was diagnosed epidural
      hematoma. INTERVENTIONS: Laminectomy and decompression surgery was performed.
      OUTCOMES: At the last follow-up, he recovered the feeling and function of lower
      limbs. A literature review was undertaken to understand the incidence and risk
      factors. The incidence of spinal hematoma in this population is high and only
      probable risk factors are reported without further research. LESSONS: Based on
      our review and the illustration of this case, AS patients have both lumbar and
      hip bony fusion. The exact bone canal caused by the lumbar puncture needle may
      play an important role in epidural hematoma. General anesthesia may be a better
      choice for this special patient cohort.

PMID- 28489778
TI  - Pancreatoduodenectomy (PD) and postoperative pancreatic fistula (POPF): A
      systematic review and analysis of the POPF-related mortality rate in 60,739
      patients retrieved from the English literature published between 1990 and 2015.
AB  - BACKGROUND: Pancreatoduodenectomy (PD) is one of the most technically demanding
      operations challenging surgeons, and a postoperative pancreatic fistula (POPF)
      can complicate an otherwise uneventful postoperative (PO) course. This review
      examined the methods and procedures used to prevent postoperative pancreatic
      fistula (POPF) after pancreatoduodenectomy (PD). METHODS: A comprehensive
      systematic search of the literature was performed using PubMed (Medline), Embase,
      Web of science, and the Cochrane databases for studies published between January
      1, 1990 and December 31, 2015. English language articles involving at least 100
      patients undergoing PDs carried out in centers performing at least 10 PDs/y were
      screened for data regarding the Grade of any POPFs according to the definition of
      the International Study Group on Pancreatic Fistula (ISGPF) and the overall rate
      of PO mortality related to POPF. RESULTS: We reviewed 7119 references through the
      major databases, and an additional 841 studies were identified by cross-checking
      the bibliographies of the full-text articles retrieved. After excluding 7379 out
      of 7960 studies, because they did not meet the eligibility criteria, the full
      texts of 581 articles were examined; 96 studies were excluded at this point,
      because they concerned partially or totally duplicate data that had already been
      reported. The remaining 485 articles were screened carefully for POPF-related
      mortality and POPF Grades as defined by the ISGPF. Of the 485 articles, 208
      reported the POPF-related PO mortality rate and 162 the Grades (A, B, and C) of
      POPFs in 60,739 and 54,232 patients, respectively. The POPF-related mortality
      rates after pancreatojejunostomy and pancreatogastrostomy were similar but were
      less (0.5% vs. 1%; P = .014) when an externally draining, trans-anastomotic stent
      was placed intraoperatively. The incidence of the different Grades of POPF Grade
      was quite variable, but Grade C POPFs were associated with a PO mortality rate of
      25.7% (range 0-100%). CONCLUSIONS: The POPF-related mortality rate has remained
      at approximately 1% over the past 25 years. Only externally draining, trans
      anastomotic stents decreased the POPF-related mortality rate. However, adequately
      designed venting drains were never tested in randomized controlled trials (RCTs).

PMID- 28489780
TI  - Prognostic and clinicopathological significance of cyclin B expression in
      patients with breast cancer: A meta-analysis.
AB  - BACKGROUND: Cyclin B plays a crucial role in cancer cell cycle progression and is
      overexpressed in many human cancers, including breast cancer. However, the
      prognostic value of cyclin B expression in breast cancer is controversial. We
      performed a meta-analysis to assess the clinicopathological and prognostic
      significance of cyclin B expression in breast cancer. METHODS: We searched
      PubMed, web of science, and Embase databases to retrieve the publications
      investigating the association between cyclin B expression and
      clinicopathological/prognostic significance in breast cancer patients. The pooled
      hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CIs) were
      used to estimate the effects. RESULTS: Ten studies with 2366 breast cancer
      patients were included to evaluate the association between cyclin B expression
      and overall survival (OS), disease-free survival (DFS), disease-specific survival
      (DSS), and clinicopathological parameters. The results showed that cyclin B
      overexpression in breast cancer patients was significantly associated with both
      poor OS (univariate analysis: HR = 2.38, 95% CI = 1.72-3.30, P < .001), DFS
      (univariate analysis: HR = 1.86, 95% CI = 1.50-2.32, P < .001; multivariate
      analysis: HR = 1.75, 95% CI = 1.22-2.52, P = .003), and DSS (multivariate
      analysis: HR = 5.42, 95% CI = 2.15-13.66, P < .001). Additionally, cyclin B
      overexpression was significantly associated with lymphatic invasion (OR = 2.58,
      95% CI = 1.03-6.46, P = .017). CONCLUSION: Cyclin B overexpression appears to be
      an independent potential prognostic marker to DSS and DFS for breast cancer.
      Further studies with large sample size are needed to dissect the relationship
      between cyclin B and clinicopathological features or prognosis of breast cancer.

PMID- 28489781
TI  - Clinical characteristics and outcomes of patients with myocarditis mimicking ST
      segment elevation myocardial infarction: Analysis of a case series.
AB  - Acute myocarditis mimicking ST-segment elevation myocardial infarction (STEMI) is
      highly deceptive for an accurate diagnosis, and a systematic study is lacking
      with regard to the clinical features and prognosis of this distinct clinical
      entity.Patients with suspected STEMI and eventually diagnosed with myocarditis by
      cardiac magnetic resonance (CMR) from January 2012 to April 2016 at Fuwai
      Hospital were identified by reviewing medical records and electronic databases.
      Follow-up was conducted by clinical visits and phone contacts in a median
      duration of 17 months.A total of 18 patients were included in the study, with 17
      males and 1 female. They were relatively young, and their mean age was 30.8
      years. 94.4% of the patients had a high prevalence of infectious prodrome, and
      inflammatory biomarkers were notably elevated in all patients. Late gadolinium
      enhancement on CMR was detected in 13 patients. Three patients underwent
      fulminant course, and left ventricular ejection fraction (LVEF) <45% on admission
      occurred in 3 patients. The median LVEF improved from 59% on admission to 65% at
      discharge (P <.001), and none developed cardiac insufficiency, heart
      transplantation, or death during a median follow-up of 17 months.Myocarditis
      mimicking STEMI is featured by young age and an existence of flu-like prodrome.
      CMR benefits the differential diagnosis of this unique clinical entity. Notably,
      patients with myocarditis mimicking STEMI had a favorable prognosis, and
      establishing an accurate diagnosis is crucial to avoid unreasonable treatments
      for them.

PMID- 28489782
TI  - Incidence and risk factors of depression after diagnosis of lung cancer: A
      nationwide population-based study.
AB  - This study aimed to explore the incidence and risk factors of depression after
      lung cancer diagnosis. Using the Taiwan National Health Insurance Research
      Database (NHIRD), incidences and risk factors of depression in lung cancer and
      nonlung cancer cohorts were analyzed.From 1998 to 2006, a total of 22,125
      patients were included in each matched cohort of lung cancer and nonlung cancer
      patients from NHIRD. The incidence of depression was higher in the lung cancer
      cohort than in the nonlung cancer cohort (1545.8 vs 1366.6 per 100,000 person
      years). An increased risk of depression was observed in the lung cancer cohort
      [adjusted hazard ratio (aHR): 1.16, 95% confidence interval (95% CI): 1.01-1.34,
      P = .0377]. In lung cancer patients, age <=50 years (aHR: 2.72, 95% CI: 2.02
      3.66, P < .0001), age 50 to 69 years (aHR: 2.34, 95% CI: 1.87-2.94, P < .0001),
      female gender (aHR: 1.50, 95% CI: 1.26-1.80, P < .0001), coronary artery disease
      (CAD) (aHR: 1.40, 95% CI: 1.08-1.82, P = .0113), and operation (aHR: 1.78, 95%
      CI: 1.46-2.16, P < .0001) were associated with an increased risk of depression.
      In addition, higher incidences of emergency room (ER) visit (4.76 vs 2.82, per
      person-year) and admission (5.73 vs 4.33, per person-year) were observed in lung
      cancer patients with depression than those without depression.Our results showed
      that early surveillance and intervention of depression should be advocated after
      a diagnosis of lung cancer.

PMID- 28489783
TI  - Clinical significance and prognostic value of Triosephosphate isomerase
      expression in gastric cancer.
AB  - Triosephosphate isomerase (TPI) is highly expressed in many human cancers and is
      involved in migration and invasion of cancer cells. However, TPI
      clinicopathological significance and prognostic value in gastric cancer (GC) are
      not yet well defined. The aim of the present work was to evaluate TPI expression
      in GC tissue and its prognostic value in GC patients.TPI expression was analyzed
      in 92 primary GC tissues and 80 adjacent normal mucosa tissues from GC patients
      undergoing gastrectomy by immunohistochemical analysis of tissue microarrays
      (TMAs). Univariate and multivariate analyses were performed to investigate TPI
      prognostic significance in GC patients.Immunohistochemical staining score showed
      that TPI expression in cancer tissues was significantly higher than in adjacent
      normal mucosa (P < .001). Univariate analysis revealed that TPI expression, depth
      of invasion, lympho node metastasis, tumor node metastasis (TNM) stage, and tumor
      diameter were associated with negative prognostic predictors for overall survival
      in GC patients (P < .05). High TPI expression represented a significant predictor
      of shorter survival in GC patients with positive lymphatic metastasis (P = .022)
      and tumor diameter >5 cm (P = .018). Cox multivariate analysis identified TPI
      expression, TNM stage, and tumor diameter as independent prognostic factors in GC
      patients.TPI expression might be considered as a novel prognostic factor to
      evaluate GC patients' survival.

PMID- 28489784
TI  - Rectal cancer: Short-term reproducibility of intravoxel incoherent motion
      parameters in 3.0T magnetic resonance imaging.
AB  - The aim of this study was to evaluate the short-term test-retest reproducibility
      of diffusion-weighted magnetic resonance imaging (DW-MRI) parameters of rectal
      cancer with 3.0T MRI.Twenty-six patients with rectal cancer underwent MRI,
      including diffusion-weighted imaging with 8 b values. Apparent diffusion
      coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters (D, pure
      diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were,
      respectively, calculated. The short-term test-retest reproducibility, the intra
      and interobserver variation of the IVIM parameters were assessed based on the
      repeatability coefficient and Bland-Altman limits of agreement.There was no
      significant intra or interobserver difference observed in the parameters on the
      same DW-MRI scan. The corresponding repeatability coefficient of intra- and
      interobserver analysis for ADC, D, f, and D* was 5.4%, 11.1%, 55.4%, and 40.3%;
      10.9%, 41.6%, 134.0%, and 177.6%, respectively. The test-retest repeatability
      coefficient for ADC, D, f, and D* was 19.1%, 24.5%, 126.3%, and 197.4%,
      respectively, greater than the intraobserver values.ADC and D have better short
      term test-retest reproducibility than f and D*. Considering the poor test-retest
      reproducibility for f and D,* variance in these 2 parameters should be
      interpreted with caution in longitudinal studies on rectal cancer in which
      treatment response and recurrence are monitored.

PMID- 28489785
TI  - Effect of psoas muscle mass after endoscopic therapy for patients with esophageal
      varices.
AB  - We aimed to investigate the impact of decrease of muscle mass on survival after
      eradication of esophageal varices (EVs) treated by endoscopic therapies as a
      primary prophylaxis in patients with liver cirrhosis (LC). In all, 177 LC
      individuals with EVs undergoing endoscopic therapies were analyzed. We
      retrospectively examined the impact of muscle mass decrease as determined by
      psoas muscle mass (PMM) at the third lumber on computed tomography (depletion of
      PMM [DPMM]) on survival as compared with serum sodium combined Model for End
      stage Liver Disease (MELD-Na). In comparison of the effects of these parameters,
      we used time-dependent receiver-operating characteristics (ROC) analysis. We also
      investigated parameters related to overall survival in the univariate and
      multivariate analyses. This study included 116 males and 61 females with a median
      age of 66 years. The median follow-up periods were 2.7 years (range 0.1-9.6
      years). In all, 110 patients (62.1%) had DPMM. The median MELD-Na score was 7.200
      (range -3.451 to 30.558). The MELD-Na score in patients with DPMM (median 7.685)
      was significantly higher than that in patients without DPMM (median 6.235) (P =
      .0212). In the multivariate analysis, presence of hepatocellular carcinoma (P <
      .0001), presence of DPMM (P < .0001), and MELD-Na >=7.2 (P = .0438) were revealed
      to be significant predictors related to overall survival. In time-dependent ROC
      analyses, all area under the ROCs for DPMM in each time point were higher than
      those for MELD-Na in the entire cohort and in patients without hepatocellular
      carcinoma at baseline (n = 133). In conclusion, for LC patients treated by
      endoscopic therapies for EVs, DPMM had stronger prognostic impact than MELD-Na.

PMID- 28489786
TI  - Bilateral carotid-cavernous fistula with spontaneous resolution: A case report
      and literature review.
AB  - RATIONALE: Bilateral carotid-cavernous fistula (CCF) is rare and serious extra
      ocular disease occurring in clinical which may result in severe complication.
      Unique manifestations and imaging examinations are important to the diagnosis.
      PATIENT CONCERNS: A case of bilateral carotid-cavernous fistula in an 60-year-old
      healthy man caused by a head injury is reported. Further clinical symptoms and
      signs and imaging examinations lead to the correct diagnosis. DIAGNOSES: Computed
      tomography angiography of the brain aroused suspicion of bilateral CCF. On
      physical examination, intraocular pressure in the right eye was 35 mm Hg, while
      the other eye was 56 mm Hg. INTERVENTIONS: After diagnosis, the patient chose
      conservative treatment for some reasons. OUTCOMES: The symptom of him had
      relieved in both eyes but no light perception in the right eye after two months
      telephone follow-up. LESSONS: Our case study demonstrated that a highly suspicion
      must be maintained when managing such patients to prevent serious consequences.
      At the same time, the early diagnosis and treatment of the disease have a
      critical relationship to the prognosis of patients, which should be paid
      attention to.

PMID- 28489787
TI  - A systematic review and meta-analysis of intravenous glucocorticoids for acute
      pain following total hip arthroplasty.
AB  - BACKGROUND: Glucocorticoids are increasingly used perioperatively, principally to
      prevent postoperative nausea and vomiting (PONV), and acute postoperative pain
      following total hip arthroplasty (THA). The authors hypothesized that
      preoperative intravenous glucocorticoids is associated with less pain scores and
      PONV without increasing the complications after THA. METHODS: Four databases
      (PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of
      Science) were searched with the limitations of randomized controlled trials
      (RCTs). The search cutoff date was set at November 6, 2016. Participants were
      patients who were prepared for primary THA. Intervention was preoperative
      intravenous glucocorticoids for postoperative pain control. Outcomes including
      the visual analog scale (VAS) scores at the postanesthesia care unit (PACU) and
      at 24 and 48 hours post operation, the occurrence of PONV and total morphine
      consumption were recorded. We calculated risk ratio (RR) with a 95% confidence
      interval (CI) for dichotomous outcomes, and the weighted mean difference (WMD)
      with a 95% CI for continuous outcomes. RESULTS: A total of 6 studies were
      evaluated, which included 297 patients who underwent hip surgery with intravenous
      glucocorticoid treatment and control patients who underwent hip surgery without
      glucocorticoid treatment. Pooled results indicated that intravenous
      glucocorticoid treatment was associated with a reduction of VAS scores at the
      PACU (WMD = -9.06, 95% CI -12.67 to -5.45, P = .000) and total morphine
      consumption by 15.68 mg (WMD = -15.68, 95% CI -24.60 to -6.75, P = .001). No
      significant difference was observed in the VAS scores at 24 and 48 hours between
      the intravenous glucocorticoid and placebo treatments. Intravenous steroids can
      decrease the occurrence of PONV (RR = 0.46, 95% CI 0.26-0.82, P = .029).
      CONCLUSION: Intravenous glucocorticoid treatment can decrease early pain
      intensity and PONV after THA. However, the evidence for the use of
      glucocorticoids is limited by the low number of studies and variation in dosing
      regimens. Thus, additional high-quality RCTs are needed to identify the optimal
      drug protocol and determine the safety of intravenous glucocorticoids.

PMID- 28489788
TI  - Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma
      leukemia undergoing allogeneic hematopoietic stem-cell transplantation: A rare
      case report: a care-compliant article.
AB  - RATIONALE: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in
      immunocompromised patients, which may lead to blindness. CMV retinitis is not an
      uncommon infectious disease in patients with immune regulatory abnormalities, for
      example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a
      patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic
      hematopoietic stem-cell transplantation (HSCT) phase is very rare. PATIENT
      CONCERNS: A case of CMV retinitis in a patient receiving immunosuppressive
      therapy as a part of ALL allogeneic HSCT is described including the pathogenesis,
      clinical signs, and therapy. DIAGNOSES: CMV retinitis. INTERVENTIONS: Ganciclovir
      intravitreal injection at weekly intervals for 4 weeks. OUTCOMES: Patient's
      vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the
      aqueous humor declined. The CMV retinitis and perivascular of retina infiltration
      regressed. LESSONS: We propose that the concentration of CMV DNA load in the
      aqueous humor could be useful in making the diagnosis and in selecting the
      optimal treatment in this kind of CMV retinitis.

PMID- 28489789
TI  - Effective and extensible feature extraction method using genetic algorithm-based
      frequency-domain feature search for epileptic EEG multiclassification.
AB  - In this paper, genetic algorithm-based frequency-domain feature search (GAFDS)
      method is proposed for the electroencephalogram (EEG) analysis of epilepsy. In
      this method, frequency-domain features are first searched and then combined with
      nonlinear features. Subsequently, these features are selected and optimized to
      classify EEG signals. The extracted features are analyzed experimentally. The
      features extracted by GAFDS show remarkable independence, and they are superior
      to the nonlinear features in terms of the ratio of interclass distance and
      intraclass distance. Moreover, the proposed feature search method can search for
      features of instantaneous frequency in a signal after Hilbert transformation. The
      classification results achieved using these features are reasonable; thus, GAFDS
      exhibits good extensibility. Multiple classical classifiers (i.e., k-nearest
      neighbor, linear discriminant analysis, decision tree, AdaBoost, multilayer
      perceptron, and Naive Bayes) achieve satisfactory classification accuracies by
      using the features generated by the GAFDS method and the optimized feature
      selection. The accuracies for 2-classification and 3-classification problems may
      reach up to 99% and 97%, respectively. Results of several cross-validation
      experiments illustrate that GAFDS is effective in the extraction of effective
      features for EEG classification. Therefore, the proposed feature selection and
      optimization model can improve classification accuracy.

PMID- 28489790
TI  - CA125 modified by PLT and NLR improves the predictive accuracy of adenomyosis
      derived pelvic dense adhesion.
AB  - To explore the value of serum levels of CA125, platelet count (PLT), neutrophil
      lymphocyte ratio (NLR), and modified CA125 markers CA125a and CA125b in
      predicting pelvic dense adhesion (PDA) associated with adenomyosis, CA125a =
      lg(CA125 * PLT * 10), CA125b = lg(CA125 * NLR).This retrospective study included
      304 patients who underwent surgery for adenomyosis. Correlations of serum levels
      of CA125, PLT, NLR, and modified CA125 markers with adenomyosis-derived PDA were
      analyzed by Logistic regression. Receiver operating characteristic curve was
      applied to assess the utility of these parameters for predicting PDA.All the
      parameters including CA125, PLT, NLR, and modified CA125 markers were positively
      correlated with PDA (P < .05 or P < .01). More importantly, CA125a was more
      specific (85.03% vs. 83.00%) and more sensitive (47.56% vs. 47.47%) than CA125
      alone for the prediction of PDA, and CA125b could also improve the predictive
      specificity of PDA (53.13% vs. 47.47%).Serum CA125, PLT, and NLR were all closely
      correlated with PDA in adenomyosis patients. CA125 modified by PLT and NLR could
      further improve the predictive accuracy of adenomyosis-derived PDA, thus
      providing more meaningful references for better-informed decisions about the mode
      of surgical access for the clinical treatment of adenomyosis.

PMID- 28489791
TI  - Effect of perioperative statin therapy on renal outcome in patients undergoing
      cardiac surgery: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Acute renal injury (AKI) is a common renal complication after cardiac
      surgery. The aim of this study was to determine the effect of perioperative
      statin therapy (PST) on postoperative renal outcome in patients undergoing
      cardiac procedures. METHODS: We searched for the reports that evaluating the
      effect of PST on renal outcomes after cardiac surgery between March 1983 and June
      2016 in the electronic database Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE/PubMed, and EMBASE/OVID. RESULTS: Nine randomized controlled
      trials (RCTs) enrolling 2832 patients, with 1419 in the PST group and 1413 in the
      control group, were included in this meta-analysis. Our results suggested that
      PST increased the incidence of postoperative renal complication (relative risk
      [RR] 1.18, 95% confidence interval [CI] 1.01-1.36, P = .03) with low
      heterogeneity (I = 30%, P = .18). Six studies with 3116 patients detected no
      significant difference in severe renal complication between PST and control
      groups (RR 1.23, 95%CI 0.84-1.79, P = .28). Postoperative serum creatinine (sCr)
      at 48 hours was shown to be higher in the PST group (mean difference [MD] 0.03,
      95% CI 0.03-0.03; P < .01). The length of hospital stay was decreased slightly by
      0.59 day in the PST group (95% CI -0.85 to -0.33; P < .01). CONCLUSIONS:
      Perioperative statin therapy seems to jeopardize short-term renal outcome in
      patients undergoing cardiac surgery, but the occurrence of severe renal
      complication was not affected.

PMID- 28489792
TI  - Eye bank prepared versus surgeon cut endothelial graft tissue for Descemet
      membrane endothelial keratoplasty: An observational study.
AB  - The purpose of this article is to examine outcomes of Descemet membrane
      endothelial keratoplasty (DMEK) performed with cornea bank (CB) prestripped
      tissue and surgeon stripped tissue (SST).This retrospective study examined
      subjects who underwent DMEK with CB or surgeon prepared tissue for Fuchs
      endothelial corneal dystrophy. Best-corrected visual acuity (BCVA), corneal
      thickness, endothelial cell count (ECC), and complications were examined before
      and throughout a 6-month postoperative period.Eleven CB and 22 SST subjects were
      included. Six months after surgery, BCVA was 20/20 or better in 36.4% of CB and
      22.7% of SST subjects (P = .43). Median logMAR BCVA was 0.10 (0.00-0.20, 20/25)
      in group CB and 0.10 (0.10-0.30, 20/25) in group SST. Median preoperative corneal
      thickness was 614.0 MUm (577.5-662.0 MUm) and 658.0 MUm (606.0-689.0 MUm) in CB
      and SST subjects, respectively (P = .37). Six months after surgery, median
      corneal thickness was lower in the CB group (571.0 MUm [478.0-592.0 MUm]), than
      in the SST group (576.0 MUm [531.0-607.0 MUm], P = .02). At 6 months, median ECC
      was 1500.0 cell/mm (1321.5-2049.0 cell/mm, 41% decrease) in group CB and 1403.0
      cell/mm (972.5-2010.7 cell/mm, 46% decrease) in group SST (P = .70). Rebubbling
      was required in 5 CB (45.5%) and 15 SST (68.2%) subjects (P = .39).Fuchs'
      dystrophy patients have good anatomic and functional DMEK results. Similar
      outcomes and complication rates occurred with eye bank and surgeon prepared donor
      tissue.

PMID- 28489793
TI  - A selective screening program for the early detection of mucopolysaccharidosis:
      Results of the FIND project - a 2-year follow-up study.
AB  - The mucopolysaccharidoses (MPSs) are underdiagnosed but they are evaluated in few
      newborn screening programs, probably due to the many challenges remaining, such
      as the identification of late-onset phenotypes. Systematic screening at the onset
      of clinical symptoms could help to early identify patients who may benefit from
      specific treatments. The aim of this prospective study was to assess a novel
      selective screening program, the FIND project, targeting patients aged 0 to 16
      years with clinical manifestations of MPS. The project was designed to increase
      awareness of these diseases among pediatricians and allow early diagnosis.From
      July 2014 to June 2016, glycosaminoglycan (GAG) levels normalized to creatinine
      levels were determined in urine-impregnated analytical paper submitted by
      pediatricians who had patients with clinical signs and/or symptoms compatible
      with MPS. When high GAG concentrations were detected, a new liquid urine sample
      was requested to confirm and identify the GAG present. When a specific form of
      MPS was suspected, enzyme activity was analyzed using blood-impregnated paper to
      determine MPS type (I, IIIB, IIIC, IVA, IVB, VI, or VII). Age-specific reference
      values for GAG were previously established using 145 urine samples from healthy
      children.GAG levels were normal in 147 (81.7%) of the 180 initial samples
      received. A liquid sample was requested for the other 33 cases (18.3%); GAG
      levels were normal in 13 of these and slightly elevated in 12, although the
      electrophoresis study showed no evidence of MPS. Elevated levels with
      corresponding low enzymatic activity were confirmed in 8 cases. The mean time
      from onset of clinical symptoms to detection of MPS was 22 months, and just 2
      cases were detected at the beginning of the project were detected with 35 and 71
      months of evolution of clinical symptoms. Our screening strategy for MPS had a
      sensitivity of 100%, a specificity of 85%, and a positive predictive value of
      24%.The FIND project is a useful and cost-effective screening method for
      increasing awareness of MPS among pediatricians and enabling the detection of MPS
      at onset of clinical symptoms.

PMID- 28489795
TI  - Effects of rational emotive behavior coaching on occupational stress and work
      ability among electronics workshop instructors in Nigeria.
AB  - BACKGROUND/OBJECTIVE: This study examined the effectiveness of rational emotive
      behavior coaching (REBC) on occupational stress and work ability in a sample of
      electronics workshop instructors in Nigeria. METHODS: A pretest-posttest control
      group design was used. The participants were 108 electronics workshop instructors
      in technical colleges in the south-east of Nigeria who met the study inclusion
      criteria. Data were collected using 3 questionnaires and analyzed using a
      repeated measure analysis of variance and Mann-Whitney U test. RESULTS: REBC led
      to a significant reduction in occupational stress experienced by the electronics
      workshop instructors in the REBC group compared to their counterparts in the
      waitlist control group. Furthermore, the scores for occupation-related irrational
      beliefs of the instructors in the REBC group were significantly lower than those
      in the waitlist control group at the end of the coaching intervention. The work
      ability of the REBC group was significantly better than that of the waitlist
      control group. Finally, the effects in the REBC group were significantly
      sustained at 3-month follow-up. CONCLUSION: REBC is a time-efficient and solution
      focused therapeutic modality for assisting occupationally stressed employees in a
      Nigerian setting. REBC can be used for improving and maintaining work ability of
      workers. The researchers hope that occupational health professionals and health
      counselors would extend this approach to tackle psychological issues limiting
      employees' effectiveness and performance in the Nigerian work environment and in
      other countries.

PMID- 28489794
TI  - Meta-analysis of studies using metformin as a reducer for liver cancer risk in
      diabetic patients.
AB  - Metformin has garnered more interest as a chemo-preventive agent given the
      increased liver cancer risk in diabetic patients. This work was undertaken to
      better understand the effect of metformin use on liver cancer risk in diabetic
      patients.A comprehensive literature search was performed in PubMed, Embase,
      BIOSIS Previews, Web of Science, and Cochrane Library through July 30, 2016. Meta
      analyses were performed using Stata version 12.0, with odds ratio (ORs) and 95%
      confidence intervals (CIs) as effect measures.Twenty-three studies were included.
      Meta-analysis of 19 studies involving 550,882 diabetic subjects suggested that
      metformin use reduced the ratio of liver cancer by 48% (OR = 0.52; 95% CI, 0.40
      0.68) compared with nonusers. The protective effect was validated in all the
      exploratory subgroup analyses, except that pooled result of post hoc analyses of
      2 randomized controlled trials found no significant difference between subjects
      with metformin and those without, with OR being 0.84 (95% CI, 0.10-6.83). After
      adjusting for hepatitis B/C virus infection, cirrhosis, obesity, behavioral
      factors, and time-related bias, the association was stable, pooled OR ranged from
      0.42 to 0.75.A protective effect for liver cancer was found in diabetic metformin
      users. However, more randomized clinical evidence is still needed to verify the
      results.

PMID- 28489796
TI  - Leptomeningeal metastasis of poorly differentiated uterine cervical adenosquamous
      carcinoma following reirradiation to metastatic vertebrae: A case report.
AB  - RATIONALE: Leptomeningeal metastasis from cervical adenosquamous carcinoma is
      extremely rare especially after radiotherapy for vertebral metastasis. PATIENT
      CONCERNS: A 52-year-old woman with International Federation of Gynecology and
      Obstetrics (FIGO) stage IIB adenosquamous carcinoma of cervix presented with
      bilateral lower limbs weakening after 2 courses radiotherapy to thoracic
      vertebral metastases. DIAGNOSES: Initial spine magnetic resonance imaging (MRI)
      showed no obvious nerve compression, and radiation myelopathy was suspected by
      the clinician. Progressive multifocal neurological signs developed one month
      after completion of spine re-irradiation. She was diagnosed with leptomeningeal
      metastasis by MRI and cerebrospinal fluid (CSF) study. INTERVENTIONS: She
      received whole brain irradiation with a dose of 30 Gy in 10 fractions. Systemic
      chemotherapy with cisplatin (50 mg/m) and topotecan (0.75 mg/m) was administered
      sequentially. OUTCOMES: She died with progressive disease two months after the
      diagnosis of leptomeningeal metastases. LESSONS: Poorly differentiated advanced
      stage cervical adenosquamous carcinoma is an aggressive neoplasm with a worse
      outcome. Leptomeningeal metastasis should be included in the differential
      diagnosis for patients with multifocal craniospinal neurological signs. A
      combination of detailed neurological examinations, MRI and CSF study allowed us
      to establish a correct diagnosis of leptomeningeal metastasis and initiate
      treatment in a timely manner.

PMID- 28489797
TI  - A previously published propofol-remifentanil response surface model does not
      predict patient response well in video-assisted thoracic surgery.
AB  - Modern anesthesia usually employs a hypnotic and an analgesic to produce
      synergistic sedation and analgesia. Two remifentanil-propofol interaction
      response surface models were used to predict sedation using Observer's Assessment
      of Alertness/Sedation (OAA/S) scores; one predicts an OAA/S <2 and the other <4.
      We hypothesized that both models would predict regained responsiveness (RR) after
      video-assisted thoracic surgery (VATS) to reduce total anesthesia time and make
      early extubation clinically relevant. We included 30 patients undergoing VATS
      received total intravenous anesthesia (TIVA) combined with thoracic epidural
      anesthesia (TEA). Pharmacokinetic profiles were calculated using Tivatrainer.
      Model predictions were compared with observations to evaluate the accuracy and
      precision of emergence model predictions. The mean (standard deviation)
      differences between when a patient responded to their name and the time when the
      model predicted a 50% probability of patient response were 30.80 +/- 17.77 and
      13.71 +/- 11.35 minutes for the OAA/S <2 model and <4 model, respectively. Both
      models had a limited ability to predict patient response in our patients. Both
      models identified target concentration pairs predicting time of RR in volunteers
      and some elective surgeries, but another model of epidural and intravenous
      anesthetic combinations may be needed to predict time of RR after VATS under TIVA
      with TEA.

PMID- 28489798
TI  - Efficacy of functional microarray of microneedles combined with topical
      tranexamic acid for melasma: A randomized, self-controlled, split-face study.
AB  - To evaluate the efficacy of a functional microarray of microneedles (MNs) plus
      topical tranexamic acid (TA) for melasma in middle-aged women in China.Thirty
      female subjects with melasma were enrolled in this study. The left or right side
      of the face was chosen randomly to be pretreated with a functional microarray of
      MNs, followed by topical 0.5% TA solution once per week for 12 weeks. The other
      half-face was the control, treated with a sham device plus topical 0.5% TA
      solution. At baseline and at weeks 4, 8, and 12 of treatment, clinical
      (photographic) evaluations and parameters determined by Visia were recorded. At
      baseline and week 12, patient satisfaction scores and the biophysical parameters
      measured by Mexameter were also recorded. Side effects were evaluated at baseline
      and at the end of the 12 weeks.In total, 28 women (93.3%) completed the study.
      The brown spots' scores measured by Visia were significantly lower on the
      combined therapy side than on the control side at 12 weeks after starting
      treatment; there was no significant difference between sides at 4 or 8 weeks.
      After 12 weeks, melanin index (MI) decreased significantly in both 2 groups, and
      the MI was significantly less on the combined side at week 12. Transepidermal
      water loss, roughness, skin hydration, skin elasticity, and erythema index showed
      no significant differences between 2 sides at baseline, 4, 8, and 12 weeks after
      treatment. Physicians' evaluations of photographs showed better results at week
      12 with combined therapy: >25% improvement was observed in the MNs plus TA side
      in 25 patients, and in the TA side in only 10 patients. Subjective satisfaction
      scores on both sides increased significantly. The participants were more
      satisfied with the results of the combined therapy side than the control side. No
      obvious adverse reactions were observed throughout the study.Combined therapy
      with a functional microarray of MNs and topical TA solution is a promising
      treatment for melasma.

PMID- 28489799
TI  - Comparison of clinical outcomes in peripartum cardiomyopathy and age-matched
      dilated cardiomyopathy: A 15-year nationwide population-based study in Asia.
AB  - Peripartum cardiomyopathy (PPCM), often classified as a form of dilated
      cardiomyopathy (DCM), is the myocardial dysfunction that occurs in late pregnancy
      and through the first few postpartum months.The aim of this study is to
      investigate the differences in the clinical outcomes of PPCM and DCM.Electronic
      medical records from 1997 to 2011 were retrieved from the Taiwan National Health
      Insurance Research Database. Patients with PPCM were compared with age- and
      clinical characteristics-matched patients with DCM. Primary outcomes were 1- and
      3-year heart failure (HF) readmission, cardiac death, all-cause mortality, and
      major adverse cardiovascular events. Secondary outcomes were myocardial
      infarction, new onset of dialysis, heart transplant, and cerebrovascular
      accident. Follow-up period was divided into "within the first year" and "after
      the first year."A total of 527,979 patients (253,166 females) were hospitalized
      with a principal diagnosis of HF during 1997 to 2011 period. After excluding
      patients aged <18 and >50 years, patients with other forms of HF, and those with
      a history of cerebrovascular accidents or coronary artery disease, 797 patients
      with PPCM and 1267 patients with DCM were evaluated. Propensity score matching
      yielded 391 patients in each group. Patients with DCM had a significantly worse
      prognosis compared to those with PPCM for all primary and secondary outcomes at
      the 1- and 3-year follow-ups. After 1 year, the HF readmission rate did not
      significantly differ between the 2 diseases, suggesting that HF medications
      should be aggressively instituted in patients with PPCM.This is the first study
      to directly compare the clinical outcomes between age-matched patients with PPCM
      and DCM. Patients with PPCM had a significantly better prognosis across all
      cardiovascular endpoints compared to patients with DCM.

PMID- 28489800
TI  - Characteristics and outcome of spontaneous bacterial meningitis in patients with
      cancer compared to patients without cancer.
AB  - In cancer patients, who are frequently immunocompromised, bacterial meningitis
      (BM) can be a severe complication, with a different presentation, etiology, and
      course, compared to patients without cancer. Our objective is to compare the
      characteristics and outcomes of BM in patients with and without cancer. A single
      center, prospective observational cohort study, conducted between 1982 and 2012,
      in a tertiary university hospital in Barcelona (Spain). The main outcome measure
      is in-hospital mortality. We evaluated 659 episodes of BM; 97 (15%) had active
      cancer. Patients with malignancies were older (median 63 (interquartile range
      [IQR] 24) vs 52 [IQR 42] years, P < .001) and more often had a Charlson
      comorbidity score of >=3 (51% vs 11%, P < .001). The classic meningitis triad
      (35% vs 50%, P = .05), fever (91% vs 96%, P = .03), neck stiffness (58% vs 78%, P
      < .001), headache (63% vs 77%) P = .003), and rash (7% vs 30%, P < .001) were
      less frequent. There was a longer interval between admission and antibiotic
      therapy (median 5 [IQR 14] vs 3 [IQR 6] hours, P < .001). Listeria meningitis was
      the commonest cause of BM (29%) and was more frequent in cancer than noncancer
      (8%, P < .001) patients, whereas meningococcal meningitis was much less frequent
      (4% vs 36%, P < .001). Overall mortality was higher in patients with cancer (31%
      vs 16%, P < .001), although cancer was not associated with an unfavorable outcome
      in the multivariate analysis (odds ratio 1.825, P = .07). Patients with
      meningitis and cancer are older and have more subtle clinical manifestations than
      patients without cancer. Listeria monocytogenes is the predominant pathogen and
      mortality is higher in cancer patients.

PMID- 28489801
TI  - A CARE-compliant case report: Lung transplantation for a Chinese young man with
      idiopathic pleuroparenchymal fibroelastosis.
AB  - RATIONAL: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung
      disease that is characterized radiologically by apical pleural thickening and
      histologically by elastic fibrosis of the visceral pleura. Although PPFE cases
      have been reported occasionally since this disease was initially described, most
      such cases have involved secondary PPFE. Idiopathic PPFE (iPPFE) cases have been
      less thoroughly studied. There are no effective medications for patients with
      iPPFE. PATIENT CONCERNS: A 34-year-old man with no asbestos or cigarette exposure
      was admitted to our ward due to worsening cough and exertional dyspnea for 10
      years. He had a "flattened thoracic cage" and bibasilar inspiratory crackles
      without finger clubbing. A series of chest computed tomography scans during the
      preceding 10 years revealed the presence of gradual, exaggerated, upper lung
      predominant, diffuse pleural thickening and dense subpleural opacification with
      traction bronchiectasis. DIAGNOSIS: He was performed with video-assisted thoracic
      surgical (VATS) lung biopsy. The pulmonary histopathologic examination showed
      thickened visceral pleura and prominent subpleural fibroelastosis, confirming the
      diagnosis of iPPFE. INTERVENTION: After the failure of treatment with prednisone
      plus cyclophosphamide and sequential pirfenidone administration, he was arranged
      with bilateral lung transplantation two years later. OUTCOMES: The patient did
      not require supplemental oxygenation anymore after he recovered from lung
      transplantation. LESSONS: Bilateral lung transplantation might be tried for the
      end-stage iPPFE cases.

PMID- 28489802
TI  - Combined effect of serum gamma-glutamyltransferase and uric acid on incidence of
      diabetes mellitus: A longitudinal study.
AB  - Gamma-glutamyltransferase (GGT) and uric acid (UA) are novel diabetes risk
      factors. However, little is known about the combined effects of GGT and UA on the
      development of diabetes. Here, we assessed the combined effects of GGT and UA on
      the development of diabetes in a Korean population.We evaluated 1983 women and
      2687 men without diabetes. From the baseline health screening to the follow-up
      examination, the development of diabetes, based on changes in GGT and UA quartile
      levels, was analyzed. Furthermore, the quartile of GGT and quartile of UA were
      analyzed together to determine any synergistic effect from the 4th quartile of
      GGT and UA on the development of diabetes.In women, the development of diabetes
      gradually increased with an increase in the circulating levels of GGT and UA. For
      the highest quartile of GGT and UA, hazard ratios of diabetes compared with the
      lowest quartile were 3.88 (95% confidence interval [CI]: 1.12-13.43, P = .032)
      and 7.58 (95% CI: 2.17-26.42, P = .002) after adjusting for confounders,
      respectively. Hazard ratios of diabetes after combining both 4th quartiles of GGT
      and UA were 5.29 (95% CI: 1.87-15.18, P = .002), as compared with the first and
      second quartiles. In men, however, the development of diabetes was not
      significantly different among the quartiles of UA.GGT and UA levels can synergize
      in predicting the development of diabetes in Korean women.

PMID- 28489803
TI  - Reproducibility analysis on shear wave elastography (SWE)-based quantitative
      assessment for skin elasticity.
AB  - Shear Wave Elastography (SWE) is an objective and non-invasive method widely used
      to quantify the tissue solidity. However, there are concerns about the accuracy
      of the skin SWE results due to the low signal-to-noise ratio (SNR) caused by
      subcutaneous fat, muscle and bone. This article analyzed the reproducibility of
      the result for skin SWE and therefore evaluated the availability of SME for skin
      elasticity involved diseases. Thirty volunteers (mean age: 37 +/- 12 years) were
      selected. SWE were taken on the skin of abdomen and the middle tibia in order to
      assess the impact of fat, muscle and bone on SWE results. Skin in the area of
      anterior and lateral tibia marked with seven parallel lines, and each line
      indicated an identical thickness of the subcutaneous fat from 1-7 mm. Intra-class
      correlation coefficients (ICC) were used to evaluate the intra-observer and inter
      observer reproducibility. The solidity of abdominal skin showed soft and small
      individual differences (12.4 +/- 2.7 kPa), whereas high shear moduli (25-48 kPa)
      were observed in the skin above tibia and tibialis anterior muscle. When the
      subcutaneous fat was thicker than 3 mm (>=3), we obtained excellent intra
      observer reproducibility (ICC range 0.78-0.98) and inter-observer reproducibility
      (ICC range 0.75-0.98). The thickness of subcutaneous fat could affect the
      reproducibility of skin SWE. The further study on skin SWE standardization should
      be taken.

PMID- 28489804
TI  - Comparison of learning performance of 2 intubating laryngeal mask airways in
      novice: A randomized crossover manikin study.
AB  - BACKGROUND: Intubating laryngeal mask airways (LMAs) such as i-gel and Aura-i
      could serve as rescue devices in resuscitation and further ensure the airway by
      facilitating trachea intubation without ventilation interruption. But data
      regarding intubating LMAs in novice are limited and skill degeneration without
      regular training has not been evaluated. So we designed this prospective
      randomized crossover manikin study to compare the learning performance of 2
      intubating LMAs (i-gel and Aura-i). METHODS: In total, 46 novice doctors
      participated in this study. After standardized training and finishing 3
      consecutive successful intubations with both LMAs on manikin, each participant
      applied intubation with both LMAs in random order for initial evaluation. To
      evaluate skill retention, participants were reassessed 90 days later on the same
      manikin without retraining between times. Primary outcome was time to successful
      ventilation (TTV). RESULTS: The TTV for i-gel was significantly shorter than Aura
      i (initial evaluation 11.8 +/- 2.9 seconds vs 22.4 +/- 5.2 seconds, 90-days
      reevaluation 14.9 +/- 3.6 seconds vs 28.9 +/- 10.0 seconds, initial evaluation, P
      = .001; second evaluation, P < .001); during re-evaluation, TTV taken for i-gel
      and Aura-i were both significantly longer (initial evaluation, P = .001; second
      evaluation, P < .001) and ease score of insertion both increased profoundly (i
      gel P = .025; Aura-i P < .001). In both assessments, participants preferred i-gel
      as easier alternative (initial evaluation, P = .001; second evaluation, P <
      .001). There was no difference in successful intubation rate, first attempt
      success rate, bronchoscopy assessment, and insertion score for 2 LMAs.
      CONCLUSION: Compared with Aura-i, i-gel showed a faster and easier intubation by
      novice doctors in this manikin study; the skill retention of intubation
      performance after 3 months was acceptable for both intubating LMAs, but TTV
      prolonged significantly.

PMID- 28489805
TI  - First experience of nDSAEK with heads-up surgery: A case report.
AB  - PURPOSE: To report a case of non-Descemet Stripping Automated Endothelial
      Keratoplasty (nDSAEK) using heads-up surgery. CASE/INTERVENTION: The case was a
      72-years-old man who had history of left eye blunt trauma since childhood. One
      year ago, the patient was diagnosed to have left posttraumatic bullous
      keratopathy. The patient underwent lt nDSAEK by using the heads-up three
      dimensional (3D) system last July. The surgery was performed with a Rescan 700
      surgical microscope (Carl Zeiss), which is integrated with intraoperative optical
      coherence tomography (iOCT) system. During surgery, the surgeon and audience wore
      3D passive polarized glasses. A 42 inch high-definition (HD) display and 2 HD
      cameras (Sony) were used. With this 3D system, the nDSAEK procedure before the
      graft insertion into the anterior chamber was easy especially with available high
      magnification. Also, using iOCT of the system enables the surgeon to detect any
      residual fluid at the donor graft-recipient interface and locate its place to be
      drained. The only disadvantage of the system was the difficulty in the detection
      of nDSAEK graft depth in the anterior chamber, which required frequent focus
      change during the surgery. Although the surgeon frequently adjusted the focus for
      clear stereoscopic view of the graft, he did not feel any eye strain or
      discomfort. All other steps of the procedure were performed without any problem
      and postoperative course of the patient was good. CONCLUSION: Using heads-up
      surgery for performing anterior segment surgeries is encouraging and promising.

PMID- 28489806
TI  - The relationship between corneal biomechanics and anterior segment parameters in
      the early stage of orthokeratology: A pilot study.
AB  - To investigate the relationship between corneal biomechanics and anterior segment
      parameters in the early stage of overnight orthokeratology.Twenty-three eyes from
      23 subjects were involved in the study. Corneal biomechanics, including corneal
      hysteresis (CH) and corneal resistance factor (CRF), and parameters of the
      anterior segment, including corneal curvature, central corneal thickness (CCT),
      and corneal sublayers' thickness, were measured at baseline and day 1 and 7 after
      wearing orthokeratology lens. One-way analysis of variance with repeated measures
      was used to compare the longitudinal changes and partial least squares linear
      regression was used to explore the relationship between corneal biomechanics and
      anterior segment parameters.At baseline, CH and CRF were positively correlated
      with CCT (r = 0.244, P = .008 for CH; r = 0.249, P < .001 for CRF), central
      stroma thickness (CST) (r = 0.241, P = .008 for CH; r = 0.244, P = .002 for CRF)
      and central Bowman layer thickness (CBT) (r = 0.138, P = .039 for CH; r = 0.171,
      P = .006 for CRF). Both CH and CRF significantly decreased from day 1 after
      orthokeratology. The corneal curvature and the epithelium thickness also
      significantly decreased, while the stromal layer thickened significantly from day
      1 after orthokeratology. There was no correlation between the changes of corneal
      biomechanics and anterior segment parameters at day 1 and 7 after
      orthokeratology.While corneal biomechanics were positively correlated with CCT,
      CST, and CBT, the changes of CH and CRF were not correlated with the changes of
      corneal curvature, CCT, and corneal sublayers' thickness in the early stage of
      orthokeratology in our study.

PMID- 28489807
TI  - Comparative study of short- and long-term outcomes of laparoscopic-assisted
      versus open rectal cancer resection during and after the learning curve period.
AB  - Laparoscopic-assisted rectal resection (LAR) has been widely used to treat rectal
      cancer. However, it has a steep learning curve. In this study, we aimed to
      investigate the effects of the learning curve on the outcomes of LAR. All
      consecutive patients with rectal cancer undergoing LAR or open resection (OR)
      between 2010 and 2015 were included in this retrospective analysis. The learning
      curve was determined, and patients were divided into 2 phases: the learning curve
      and the expert period. The short-term perioperative data in the 2 phases and the
      long-term survival in the learning phase were compared between the LAR and OR
      groups. A total of 491 patients were included in this study. Inflection of the
      learning curve based on the operation time of LAR was at the 40th case. A total
      of 233 patients underwent surgery (112 LAR and 121 OR) during the learning
      period. In this period, LAR had a longer operation time, less blood loss, and a
      higher total cost (all P < .05). The 3-year overall survival rates between the
      LAR and OR groups were similar (69.74% vs 75%; P = .32). A total of 258 patients
      underwent surgery (169 LAR and 89 OR) during the expert period. Significant
      differences in total cost, estimated blood loss, postoperative hospital stay, and
      recovery of bladder and bowel functions were identified in this period (all P <
      .05). LAR during the learning period has fewer benefits in terms of postoperative
      recovery than OR. However, the long-term outcomes are equivalent.

PMID- 28489808
TI  - Mental health status after living donor hepatectomy.
AB  - Donor safety and preservation of donor health after living liver donation are of
      paramount importance. In addition, the preoperative mental state of a donor is an
      important factor in determining the psychological impact of donor hepatectomy.
      Thus, we aimed to explore the mental health status of living liver donors after
      hepatectomy. We enrolled 60 donors who were scheduled to undergo living donor
      hepatectomy during the period January 2014 to March 2015 at a single medical
      center. Mental health status was measured before and 3 months after surgery using
      3 self-report questionnaires, namely the Center for Epidemiologic Studies
      Depression Scale (CES-D) to assess depressive symptoms, the World Health
      Organization Quality of Life (WHOQOL-BREF) questionnaire to measure quality of
      life, and the Chinese Health Questionnaire (CHQ) to screen for minor psychiatric
      disorders. A comparison of the pre- and postdonation CES-D scores revealed a
      significant reduction in depressive symptoms after surgery (P = .031). There were
      significant improvements in the physical health domain (P = .031), the
      psychological health domain (P = .005), the social relationships domain (P =
      .005), and the environmental health domain (P = .010) of the WHOQOL-BREF. There
      were no significant changes in CHQ scores after donor hepatectomy (P = .136). All
      donors reported that they would donate again if required. Approximately one-third
      (33.3%) of donors experienced more pain than they had anticipated in the
      immediate postoperative period, and 20.0% of donors had complications after donor
      hepatectomy. Donor mental health status tended to improve as donors regained
      physical function during the 1st 3 months of recovery. Long-term monitoring of
      living donors' mental health is needed to minimize the adverse psychological
      outcomes of living liver donation.

PMID- 28489809
TI  - Cannabis-induced bullous lung disease leading to pneumothorax: Case report and
      literature review.
AB  - RATIONALE: Marijuana use has been increasing in the United States among college
      students and young adults. Marijuana use has been associated with bullous lung
      disease which can lead to pneumothorax. There are other recreational drugs like
      methylphenidate, cocaine and heroin which have been associated with pneumothorax.
      PATIENT CONCERNS: We present a case of a 30-year-old man with spontaneous
      pneumothorax associated with marijuana use. The patient had no medical conditions
      and presented to the emergency room with chest pain. The physical examination
      revealed decreased breath sound on the right side of the chest. DIAGNOSES: Bed
      side ultrasound of chest showed stratosphere sign, absent lung sliding;
      consistent with right-sided pneumothorax. INTERVENTIONS AND OUTCOMES: The patient
      underwent placement of a chest tube. Computed tomography chest scans performed on
      day two also showed bullous lung disease in the right lung. Serial x-rays of the
      chest showed re-expansion of the lung. LESSONS: Despite the beneficial effects of
      Marijuana there are deleterious effects which are emphasized here. This case
      highlights the need for further studies to establish the relationship between
      marijuana use and lung diseases in the absence of nicotine use.

PMID- 28489810
TI  - A case report of hereditary neuropathy with liability to pressure palsies
      accompanied by type 2 diabetes mellitus and psoriasis.
AB  - RATIONALE: Hereditary neuropathy with liability to pressure palsy (HNPP) is an
      episodic, multifocal neuropathy, with a typical clinical presentation of
      recurrent transient pressure palsies, which is induced by a PMP22 deletion.
      Another neuropathy caused by a PMP22 duplication is Charcot-Marie-Tooth disease
      type 1A (CMT1A). PMP22 is a gene coding a protein called peripheral myelin
      protein 22 (PMP22), which plays an essential role in the formation and
      maintenance of compact myelin. Coexistence of type 2 diabetes mellitus (T2DM) and
      CMT1A has been reported in many work, however HNPP patients with T2DM are rare,
      and comorbidity of HNPP and psoriasis has not been reported previously.
      Electrophysiological features of HNPP has been found progressing with aging.
      Patient concerns: Here we present a 20-year-old man who exhibited lower extremity
      weakness and foot drop as the initial manifestation. DIAGNOSES: HNPP was
      diagnosed on the basis of clinical features, positive sural nerve biopsy
      findings, and genetic testing results. Moreover, physical examination,
      blood/urine glucose test, and diabetes-related autoantibodies investigations
      demonstrated that he had psoriasis and T2DM. The electrophysiological
      manifestations revealed profound demyelinating injuries and axonal injuries in
      distal peripheral nerves and facial nerves, which were more severe than general
      HNPP cases. INTERVENTIONS: The young patient was treated with continuous
      subcutaneous insulin infusion and blood glucose monitoring, and then transferred
      to oral acarbose therapy. The psoriatic lesions were treated with calcipotriol
      ointment. OUTCOMES: In the follow-up, the right leg weakness was alleviated, and
      his gait was improved. LESSONS: The findings indicate that diabetes mellitus may
      have an impact on the severity of HNPP. Physicians should consider that worsening
      of symptoms might result from newly diagnosed diabetes mellitus while treating
      patients with HNPP.

PMID- 28489811
TI  - Intravascular large b-cell lymphoma diagnosed via transjugular liver biopsy in a
      patient with liver dysfunction and thrombocytopenia: A Case Report.
AB  - RATIONALE: Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare
      subtype of large B-cell lymphoma characterized by the presence of lymphoma cells
      within the lumen of small blood vessels. IVLBCL presents with nonspecific
      symptoms such as fever, weight loss, and bleeding. Because of its rarity and
      unremarkable clinical presentation, a timely diagnosis is very challenging.
      PATIENT CONCERNS: A 71-year-old Korean man complained of fever, but apart from
      pretibial pitting edema and mild thrombocytopenia, the physical examination and
      laboratory test findings were unremarkable. DIAGNOSES: A bone marrow biopsy was
      also nonspecific. The fever persisted and his thrombocytopenia became more
      pronounced, prompting further laboratory tests that indicated infiltrative liver
      disease. INTERVENTIONS: Because of coagulopathy, a liver biopsy was performed
      using a transjugular instead of apercutaneous approach. OUTCOMES: The procedure
      was performed without complications, and the pathologic examination findings were
      consistent with IVLBCL. Unfortunately, the patient died because of disease
      progression before treatment could be administered. LESSONS: Given that an early
      diagnosis can affect the prognosis of IVLBCL, quickly and safely obtaining a
      biopsy specimen is very important. The case presented here shows that a liver
      biopsy obtained via a transjugular approach is safe and could be preferentially
      considered when there is a high risk for bleeding complications.

PMID- 28489812
TI  - Are public health physicians still needed in medically underserved rural areas in
      Korea?
AB  - Public health physicians (PHPs) are certified physicians who are serving in a
      public health center or subcenter in a rural village, instead of serving in the
      military. However, the PHP program has recently become the subject of a profound
      debate, over 30 years after its adoption. In this study, we attempted to
      ascertain physicians' perspectives on the PHP program, including: whether the PHP
      policy should continue; if they agree on changing the role of PHPs in healthcare;
      what would be the desired role of PHPs; and what resources would be required and
      what possible barriers would be anticipated under the changes. We selected 88
      PHPs as our study sample using quota sampling. Over 60% of respondents were in
      support of continuing the PHP program. They believed some remote islands and
      mountainous areas are still in need of public healthcare doctors. However, some
      of them believed that the role of PHPs should be changed to take on community
      health promotion, because the problem of medically underserved rural areas has
      almost been resolved. However, people living in rural areas are ageing and
      suffering from a lack of education and health information. In particular, in
      order to successfully transition into new roles, PHPs must be provided with
      continuing education and professional development programs covering their new
      responsibilities. It is imperative to refurbish the PHP program to meet current
      needs and continue its central role in public healthcare.

PMID- 28489813
TI  - Implementing a novel model for hospice and palliative care in the emergency
      department: An experience from a tertiary medical center in Taiwan.
AB  - Hospice and palliative care has been recognized as an essential part of emergency
      medicine; however, there is no consensus on the optimal model for the delivery of
      hospice and palliative care in the emergency department (ED). Therefore, we
      conducted a novel implementation in a tertiary medical center in Taiwan. In the
      preintervention period, we recruited a specialist for hospice and palliative
      medicine in the ED to lead our intervention. In the early stage of the
      intervention, starting on July 1, 2014, we encouraged and funded ED physicians
      and nurses to receive training for hospice and palliative medicine and residents
      of emergency medicine to rotate to the hospice ward. In the late stage of the
      intervention, we initiated educational programs in the ED, an interdisciplinary
      meeting with the hospice team every month, sharing information and experience via
      a cell phone communication app, and setting aside an emergency hospice room for
      end-of-life patients. We compared the outcomes among pre-, during, and
      postintervention periods. Compared with 4 in the preintervention period, the
      cases of do not resuscitate (DNR) per month increased significantly to 30.1 in
      the early stage of intervention, 23.9 in late stage of intervention, and 34.6 in
      the postintervention period (all P < .001 compared with the preintervention
      period). Compared with 10.8% in the preintervention period, the ratio of DNR
      orders signed in the ED/total DNR orders signed in the study hospital was
      increased to 17.1% in early stage of intervention, 12.5% in late stage of
      intervention, and 22.8% in postintervention. Compared with zero in
      preintervention and early intervention, the cases of consultation with the
      hospice team increased significantly to 19 cases per month in the late stage of
      intervention and postintervention. The ability of nurses in hospice and
      palliative care, including knowledge and the timing and method of consultation
      with the hospice team, was also significantly improved. We successfully
      implemented a novel model of hospice and palliative care in the ED via a
      champion, education, and close collaboration with the hospice team, which could
      be an important reference for other EDs and intensive care unit in the future.

PMID- 28489814
TI  - Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting
      Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel
      Disease.
AB  - BACKGROUND This study aimed to investigate the diagnostic values of serum levels
      of Hcy and UA for predicting vascular mild cognitive impairment (VMCI) in
      patients with cerebral small vessel disease (SVD). MATERIAL AND METHODS We
      selected 172 cerebral SVD patients and divided them into a VMCI group and a non
      VMCI group. Eighty-six healthy individuals without nervous system diseases were
      selected as the control group. Enzymatic cycling method was performed to detect
      serum Hcy and UA levels. Serum levels of folic acid (FOA) and vitamin B12
      (VitB12) were detected by chemiluminescence immunoassay. Montreal cognitive
      assessment (MoCA) was applied to evaluate the cognitive function. The ROC curve
      was used to evaluate the diagnostic values of serum Hcy and UA levels for
      predicting VMCI. Logistic regression analysis was used to determine the possible
      risk factors. RESULTS Compared with the non-VMCI and control groups, serum FOA
      and VitB12 levels were lower and serum Hcy and UA levels were higher in the VMCI
      group. AUC values of serum Hcy and UA levels were 0.703 and 0.829, respectively.
      Serum Hcy and UA levels were negatively correlated with serum FOA and VitB12
      levels, total MoCA score, and subscores on visuospatial ability and executive
      function, on language ability and on delayed recall, and they were positively
      correlated with serum cholesterol (CH) level. Serum Hcy and UA levels were
      indicated as risk factors for VMCI in cerebral SVD patients. CONCLUSIONS These
      results suggest that serum Hcy and UA levels may serve as predictive factors for
      VMCI in cerebral SVD patients.

PMID- 28489815
TI  - Common genetic variation drives molecular heterogeneity in human iPSCs.
AB  - Technology utilizing human induced pluripotent stem cells (iPS cells) has
      enormous potential to provide improved cellular models of human disease. However,
      variable genetic and phenotypic characterization of many existing iPS cell lines
      limits their potential use for research and therapy. Here we describe the
      systematic generation, genotyping and phenotyping of 711 iPS cell lines derived
      from 301 healthy individuals by the Human Induced Pluripotent Stem Cells
      Initiative. Our study outlines the major sources of genetic and phenotypic
      variation in iPS cells and establishes their suitability as models of complex
      human traits and cancer. Through genome-wide profiling we find that 5-46% of the
      variation in different iPS cell phenotypes, including differentiation capacity
      and cellular morphology, arises from differences between individuals.
      Additionally, we assess the phenotypic consequences of genomic copy-number
      alterations that are repeatedly observed in iPS cells. In addition, we present a
      comprehensive map of common regulatory variants affecting the transcriptome of
      human pluripotent cells.

PMID- 28489816
TI  - Endothelial TLR4 and the microbiome drive cerebral cavernous malformations.
AB  - Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for
      which no effective medical therapies yet exist. CCMs arise from the loss of an
      adaptor complex that negatively regulates MEKK3-KLF2/4 signalling in brain
      endothelial cells, but upstream activators of this disease pathway have yet to be
      identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut
      microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram
      negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or
      pharmacologic blockade of TLR4 signalling prevents CCM formation in mice.
      Polymorphisms that increase expression of the TLR4 gene or the gene encoding its
      co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ
      free mice are protected from CCM formation, and a single course of antibiotics
      permanently alters CCM susceptibility in mice. These studies identify unexpected
      roles for the microbiome and innate immune signalling in the pathogenesis of a
      cerebrovascular disease, as well as strategies for its treatment.

PMID- 28489817
TI  - Selectivity determinants of GPCR-G-protein binding.
AB  - The selective coupling of G-protein-coupled receptors (GPCRs) to specific G
      proteins is critical to trigger the appropriate physiological response. However,
      the determinants of selective binding have remained elusive. Here we reveal the
      existence of a selectivity barcode (that is, patterns of amino acids) on each of
      the 16 human G proteins that is recognized by distinct regions on the
      approximately 800 human receptors. Although universally conserved positions in
      the barcode allow the receptors to bind and activate G proteins in a similar
      manner, different receptors recognize the unique positions of the G-protein
      barcode through distinct residues, like multiple keys (receptors) opening the
      same lock (G protein) using non-identical cuts. Considering the evolutionary
      history of GPCRs allows the identification of these selectivity-determining
      residues. These findings lay the foundation for understanding the molecular basis
      of coupling selectivity within individual receptors and G proteins.

PMID- 28489818
TI  - A Wnt-producing niche drives proliferative potential and progression in lung
      adenocarcinoma.
AB  - The heterogeneity of cellular states in cancer has been linked to drug
      resistance, cancer progression and the presence of cancer cells with properties
      of normal tissue stem cells. Secreted Wnt signals maintain stem cells in various
      epithelial tissues, including in lung development and regeneration. Here we show
      that mouse and human lung adenocarcinomas display hierarchical features with two
      distinct subpopulations, one with high Wnt signalling activity and another
      forming a niche that provides the Wnt ligand. The Wnt responder cells showed
      increased tumour propagation ability, suggesting that these cells have features
      of normal tissue stem cells. Genetic perturbation of Wnt production or signalling
      suppressed tumour progression. Small-molecule inhibitors targeting essential
      posttranslational modification of Wnt reduced tumour growth and markedly
      decreased the proliferative potential of lung cancer cells, leading to improved
      survival of tumour-bearing mice. These results indicate that strategies for
      disrupting pathways that maintain stem-like and niche cell phenotypes can
      translate into effective anti-cancer therapies.

PMID- 28489819
TI  - Predictive compound accumulation rules yield a broad-spectrum antibiotic.
AB  - Most small molecules are unable to rapidly traverse the outer membrane of Gram
      negative bacteria and accumulate inside these cells, making the discovery of much
      needed drugs against these pathogens challenging. Current understanding of the
      physicochemical properties that dictate small-molecule accumulation in Gram
      negative bacteria is largely based on retrospective analyses of antibacterial
      agents, which suggest that polarity and molecular weight are key factors. Here we
      assess the ability of over 180 diverse compounds to accumulate in Escherichia
      coli. Computational analysis of the results reveals major differences from the
      retrospective studies, namely that the small molecules that are most likely to
      accumulate contain an amine, are amphiphilic and rigid, and have low globularity.
      These guidelines were then applied to convert deoxynybomycin, a natural product
      that is active only against Gram-positive organisms, into an antibiotic with
      activity against a diverse panel of multi-drug-resistant Gram-negative pathogens.
      We anticipate that these findings will aid in the discovery and development of
      antibiotics against Gram-negative bacteria.

PMID- 28489820
TI  - Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks.
AB  - Nutrient signalling integrates and coordinates gene expression, metabolism and
      growth. However, its primary molecular mechanisms remain incompletely understood
      in plants and animals. Here we report unique Ca2+ signalling triggered by nitrate
      with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots.
      A nitrate-sensitized and targeted functional genomic screen identifies subgroup
      III Ca2+-sensor protein kinases (CPKs) as master regulators that orchestrate
      primary nitrate responses. A chemical switch with the engineered mutant
      CPK10(M141G) circumvents embryo lethality and enables conditional analyses of
      cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated
      regulatory and developmental programs. Nitrate-coupled CPK signalling
      phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify
      the reprogramming of gene sets for downstream transcription factors,
      transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox,
      signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7
      mutants similarly impair nitrate-stimulated system-wide shoot growth and root
      establishment. The nutrient-coupled Ca2+ signalling network integrates
      transcriptome and cellular metabolism with shoot-root coordination and
      developmental plasticity in shaping organ biomass and architecture.

PMID- 28489821
TI  - Whole-brain serial-section electron microscopy in larval zebrafish.
AB  - High-resolution serial-section electron microscopy (ssEM) makes it possible to
      investigate the dense meshwork of axons, dendrites, and synapses that form
      neuronal circuits. However, the imaging scale required to comprehensively
      reconstruct these structures is more than ten orders of magnitude smaller than
      the spatial extents occupied by networks of interconnected neurons, some of which
      span nearly the entire brain. Difficulties in generating and handling data for
      large volumes at nanoscale resolution have thus restricted vertebrate studies to
      fragments of circuits. These efforts were recently transformed by advances in
      computing, sample handling, and imaging techniques, but high-resolution
      examination of entire brains remains a challenge. Here, we present ssEM data for
      the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post
      fertilization. Our approach utilizes multiple rounds of targeted imaging at
      different scales to reduce acquisition time and data management requirements. The
      resulting dataset can be analysed to reconstruct neuronal processes, permitting
      us to survey all myelinated axons (the projectome). These reconstructions enable
      precise investigations of neuronal morphology, which reveal remarkable bilateral
      symmetry in myelinated reticulospinal and lateral line afferent axons. We further
      set the stage for whole-brain structure-function comparisons by co-registering
      functional reference atlases and in vivo two-photon fluorescence microscopy data
      from the same specimen. All obtained images and reconstructions are provided as
      an open-access resource.

PMID- 28489823
TI  - Corrigendum: The genome of Chenopodium quinoa.
AB  - This corrects the article DOI: 10.1038/nature21370.

PMID- 28489824
TI  - Corrigendum: Earth's first stable continents did not form by subduction.
AB  - This corrects the article DOI: 10.1038/nature21383.

PMID- 28489822
TI  - TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2
      signalling.
AB  - The mechanistic target of rapamycin (mTOR) has a key role in the integration of
      various physiological stimuli to regulate several cell growth and metabolic
      pathways. mTOR primarily functions as a catalytic subunit in two structurally
      related but functionally distinct multi-component kinase complexes, mTOR complex
      1 (mTORC1) and mTORC2 (refs 1, 2). Dysregulation of mTOR signalling is associated
      with a variety of human diseases, including metabolic disorders and cancer. Thus,
      both mTORC1 and mTORC2 kinase activity is tightly controlled in cells. mTORC1 is
      activated by both nutrients and growth factors, whereas mTORC2 responds primarily
      to extracellular cues such as growth-factor-triggered activation of PI3K
      signalling. Although both mTOR and GbetaL (also known as MLST8) assemble into
      mTORC1 and mTORC2 (refs 11, 12, 13, 14, 15), it remains largely unclear what
      drives the dynamic assembly of these two functionally distinct complexes. Here we
      show, in humans and mice, that the K63-linked polyubiquitination status of GbetaL
      dictates the homeostasis of mTORC2 formation and activation. Mechanistically, the
      TRAF2 E3 ubiquitin ligase promotes K63-linked polyubiquitination of GbetaL, which
      disrupts its interaction with the unique mTORC2 component SIN1 (refs 12, 13, 14)
      to favour mTORC1 formation. By contrast, the OTUD7B deubiquitinase removes
      polyubiquitin chains from GbetaL to promote GbetaL interaction with SIN1,
      facilitating mTORC2 formation in response to various growth signals. Moreover,
      loss of critical ubiquitination residues in GbetaL, by either K305R/K313R
      mutations or a melanoma-associated GbetaL(DeltaW297) truncation, leads to
      elevated mTORC2 formation, which facilitates tumorigenesis, in part by activating
      AKT oncogenic signalling. In support of a physiologically pivotal role for OTUD7B
      in the activation of mTORC2/AKT signalling, genetic deletion of Otud7b in mice
      suppresses Akt activation and Kras-driven lung tumorigenesis in vivo.
      Collectively, our study reveals a GbetaL-ubiquitination-dependent switch that
      fine-tunes the dynamic organization and activation of the mTORC2 kinase under
      both physiological and pathological conditions.

PMID- 28489827
TI  - Cancer: Tumours build their niche.

PMID- 28489826
TI  - A rhodopsin in the brain functions in circadian photoentrainment in Drosophila.
AB  - Animals partition their daily activity rhythms through their internal circadian
      clocks, which are synchronized by oscillating day-night cycles of light. The
      fruitfly Drosophila melanogaster senses day-night cycles in part through
      rhodopsin-dependent light reception in the compound eye and photoreceptor cells
      in the Hofbauer-Buchner eyelet. A more noteworthy light entrainment pathway is
      mediated by central pacemaker neurons in the brain. The Drosophila circadian
      clock is extremely sensitive to light. However, the only known light sensor in
      pacemaker neurons, the flavoprotein cryptochrome (Cry), responds only to high
      levels of light in vitro. These observations indicate that there is an additional
      light-sensing pathway in fly pacemaker neurons. Here we describe a previously
      uncharacterized rhodopsin, Rh7, which contributes to circadian light entrainment
      by circadian pacemaker neurons in the brain. The pacemaker neurons respond to
      violet light, and this response depends on Rh7. Loss of either cry or rh7 caused
      minor defects in photoentrainment, whereas loss of both caused profound
      impairment. The circadian photoresponse to constant light was impaired in rh7
      mutant flies, especially under dim light. The demonstration that Rh7 functions in
      circadian pacemaker neurons represents, to our knowledge, the first role for an
      opsin in the central brain.

PMID- 28489825
TI  - Intratumoural heterogeneity generated by Notch signalling promotes small-cell
      lung cancer.
AB  - The Notch signalling pathway mediates cell fate decisions and is tumour
      suppressive or oncogenic depending on the context. During lung development, Notch
      pathway activation inhibits the differentiation of precursor cells to a
      neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung
      cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of
      ectopic Notch activation indicate that Notch signalling is tumour suppressive.
      Here we show that Notch signalling can be both tumour suppressive and pro
      tumorigenic in small-cell lung cancer. Endogenous activation of the Notch pathway
      results in a neuroendocrine to non-neuroendocrine fate switch in 10-50% of tumour
      cells in a mouse model of small-cell lung cancer and in human tumours. This
      switch is mediated in part by Rest (also known as Nrsf), a transcriptional
      repressor that inhibits neuroendocrine gene expression. Non-neuroendocrine Notch
      active small-cell lung cancer cells are slow growing, consistent with a tumour
      suppressive role for Notch, but these cells are also relatively chemoresistant
      and provide trophic support to neuroendocrine tumour cells, consistent with a pro
      tumorigenic role. Importantly, Notch blockade in combination with chemotherapy
      suppresses tumour growth and delays relapse in pre-clinical models. Thus, small
      cell lung cancer tumours generate their own microenvironment via activation of
      Notch signalling in a subset of tumour cells, and the presence of these cells may
      serve as a biomarker for the use of Notch pathway inhibitors in combination with
      chemotherapy in select patients with small-cell lung cancer.

PMID- 28489828
TI  - Ageing: Tools to eliminate senescent cells.

PMID- 28489830
TI  - [Clinical and laboratory characteristics of patients with pulmonary hypertension
      and pulmonary vascular complications hospitalized at the Instituto Nacional de
      Salud del Nino].
AB  - : The hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHN) are
      distinct pulmonary vascular complications of portal hypertension (PHT) and are
      associated with increased morbidity and mortality. OBJECTIVES: To describe the
      clinical and laboratory characteristics of patients with pulmonary hypertension
      and pulmonary vascular complications hospitalized at the Instituto Nacional de
      Salud del Nino. MATERIALS AND METHODS: We included patients with HTP hospitalized
      from January 2012 to June 2013 and that during its evolution progressed with SHP
      or HTPP. For analysis, they were divided into a first group of patients with
      liver cirrhosis and a second group with extrahepatic portal vein obstruction.
      RESULTS: Of 22 patients with HPT 45.5% were male and the age range was between 1
      month and 17 years. The etiology in the group of cirrhosis (n=14) was: autoimmune
      hepatitis (35.7%), cryptogenic cirrhosis (35.7%), inborn error of metabolism
      (14.3%), chronic viral hepatitis C (7.15%) virus and atresia extra-hepatic bile
      ducts (7.15%). Pulmonary vascular complications more frequently occurred in
      patients with liver cirrhosis (1 case of HPS and a case of PPHTN). They most
      often dyspnea, asthenia, edema, malnutrition, ascites, hypersplenism and
      gastrointestinal bleeding from esophageal varices was found. Also, they had
      elevated ALT values, alkaline phosphatase and serum albumin values decreased.
      CONCLUSIONS: In children with pulmonary hypertension, pulmonary vascular
      complications are rare. In the evaluation of these patients pulse oximetry should
      be included to detect hypoxemia and ubsequently a Doppler echocardiography and
      contrast echocardiography necessary. Dueto the finding of systolic pulmonary
      hypertension it is necessary to perform right heart catheterization.

PMID- 28489831
TI  - [Relationship between the frequency of work-related stress and prevalence of
      functional dyspepsia in Lima Geriatric Army Hospital].
AB  - OBJECTIVE: To determine the relationship between the frequency of work-related
      stress and prevalence of functional dyspepsia in a sample of 218 military older
      50 years in 2010 in Lima Military Hospital Geriatric. MATERIALS AND METHODS:
      Descriptive and explanatory study and for the data collection on stress, were
      used the Vital Events Scale Holmes-Rahe and clinical records for clinical and
      upper endoscopy registration that comply the criteria of Rome III for functional
      dyspepsia. For processing and data analysis the statistical software package SPSS
      (Statistical Package for Social Sciences) was used. RESULTS: 100% of military
      showed some level of work stress during the study year; thus, 36.7% had a high
      level, 31.2% medium or moderate level, and 32.1% had low stress level; these
      percentages medium and high stress levels accounted for 67.9%. These results
      establish that job stress is a common discomfort in the study population
      (tabulated Chi2 = 3.841, chi2 observed = 27,908). Regarding functional dyspepsia
      prevalence of 37.2%, which indicates that it is a common condition in those
      military (tabular Z = 1.96, Z c = 9.163) it was determined. CONCLUSIONS: There is
      a significant relationship between the frequency of work-related stress and
      prevalence of functional dyspepsia in military activity in older than 50 years
      (tabulated Chi2 = 5.991, chi2 observed = 28,878, contingency coefficient =
      0.342).

PMID- 28489832
TI  - Caustic ingestion in children in south of Iran. Retrospective study from Shiraz -
      Iran.
AB  - : Caustic ingestion is a major health concern in both developed and developing
      countries, that may lead to serious esophageal injury. The clinical presentation
      of caustic ingestion in children vary from asymptomatic to serious and fatal
      sequelae, such as perforation and stricture formation. OBJECTIVE: Due to the lack
      of a comprehensive study in our area, this study has evaluated clinical and
      endoscopic manifestations and complications of caustic ingestion in children in
      south of Iran. MATERIALS AND METHODS: In this retrospective study, we reviewed 75
      children with caustic ingestion who admitted in Nemazee Hospital of Shiraz
      University of Medical Science during 6 years (2006-2011). Sign and symptoms were
      recorded for each case. RESULTS: The most common symptoms were dysphagia, oral
      lesions, vomiting, and drooling. Esophageal injuries were detected in both acid
      and alkali ingestion, but gastric injuries was significantly more in acid
      ingestion. During follow up period, 20% of all cases developed esophageal
      stricture. CONCLUSION: Dysphagia, oral lesions, vomiting, and drooling were the
      most common findings.Esophageal stricture was found in 20% of cases during 3
      months of follow up.

PMID- 28489833
TI  - [Impact of infectious postoperative complications in the long term survival of
      patients gastrectomized for gastric carcinoma with curative intent].
AB  - OBJECTIVE: To determine the impact of postoperative infectious complications in
      the long term survival of patients gastrectomized for gastric carcinoma with
      curative intent. MATERIALS AND METHODS: The present cohort study evaluated a
      series of 79 patients diagnosed with resectable advanced gastric carcinoma with
      curative intent. They were grouped in: Group A (N=28): patients with
      postoperative infectious complications and Group B (N=51): patients who did not
      develop postoperative infectious complications. The study covered the years 2008
      2013. RESULTS: In group A, the survival rates at 1, 3 and 5 years was 74%, 74%
      and 47.6% respectively. In group B, the survival rates at 1, 3 and 5 years was
      80.3%, 56% and 49.8% respectively (p=0.365). The main postoperative infectious
      complications not related to the surgical technique were pneumonia (20.3%),
      followed by urinary tract infection (3.8%). The main postoperative infectious
      complications related to surgical technique was sepsis (n=5), two of which were
      related to dehiscence esophagojejunal anastomosis, two bye gastroyeyunal fistula,
      another bye enterocutaneous fistula and one patient who presented abscess and
      necrosis peripancreatic's tissue. CONCLUSIONS: There was no impact on survival at
      5 years in patients with postoperative infectious complications after gastrectomy
      with curative intent. However, further studies should be carried over.

PMID- 28489834
TI  - Endoscopic gastrostomy: critical analysis in a regional referral hospital.
AB  - INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a safe and effective
      endoscopic surgical procedure for enteral access and gastrointestinal
      decompression, and it is an excellent alternative to surgical gastrostomy. There
      are various clinical indications and these mainly include the need for prolonged
      enteral nutritional support due to complications from neurological, geriatric and
      oncological diseases and decompression of the gastrointestinal tract. Although
      safe and effective, a number of possible complications relating to the time
      (early or late complications) and severity (minor or major complications) may
      occur. OBJECTIVE: To evaluate the indications and complications relating to PEG
      among selected patients at the digestive endoscopy service of a regional referral
      hospital. MATERIALS AND METHODS: A retrospective study on patients who underwent
      PEG between May 2013 and April 2015 was conducted. The patients were identified
      through searching the medical records and using a standardized data form.
      RESULTS: 53 cases were analyzed. The average age was 70.47 years and 60.37% of
      the patients werewomen. The main indication identified was the need for enteral
      nutritional support, and 73.58% of these indications were derived from
      neurological complications, 15.09% from geriatric complications and 9.43% from
      oncological complications and 1.88% were due to gastrointestinal decompression.
      Complications occurred in 24.52% of the cases: 23.07% were major and 76.93% were
      minor. Regarding the time, there were eight cases of late complications and five
      of early complications. CONCLUSION: PEG was shown to be an effective and safe
      method for enteral access. The indication and complication rates were similar to
      those reported in the literature.

PMID- 28489835
TI  - [Knowing an infrequent complication of endoscopic retrograde
      cholangiopancreatography].
AB  - OBJECTIVE: Describe the clinical and tomographic characteristics in relation to
      the extra peritoneal distribution of collections and air in patients with
      periampullary perforation after performing endoscopic retrograde
      cholangiopancreatography (ERCP) with or without sphincterotomy. MATERIALS AND
      METHODS: Observational, descriptive study in patients with periampullary
      perforation after ERCP with or without sphincterotomy, treated in the Pancreas
      Surgery Service at Edgardo Rebagliati Martins Hospital, Lima, Peru between
      January 2013 and January 2015. RESULTS: Ten patients with periampullary
      perforation after ERCP were included. 40% were male. The mean age was 47.2 years.
      100% showed abdominal pain, fever 70%, 60% had jaundice, oral intolerance and
      vomiting. In 100% of cases the description of the procedure was for
      choledocolithiasis. Difficult cannulation is described in 80% of cases. Air or
      fluid was found in 90% in the right anterior pararenal space and the right
      perirenal, and the place where air or liquid is distributed less frequently was
      right extraperitoneal pelvis with 20%, in no caserevealed air in the mediastinum.
      CONCLUSIONS: The finding of a liquid collection and / or air in the
      retroperitoneal space right after ERCP without further involvement of the
      pancreatic gland should make us think of periampullary perforation, especially if
      you are in the right anterior pararenal space and perirenal space. This entity we
      call bilioretroperitoneo.

PMID- 28489836
TI  - Epidemiological aspects of endoscopic resections of colorectal polyps in patients
      at an endoscopy training center in the Santos region, Brasil.
AB  - INTRODUCTION: Colorectal polyps are structures that project from the surface of
      the mucosal layer of the large intestine. They are classified as neoplastic or
      non-neoplastic. Early detection of pre-neoplastic lesions is important for
      preventing colorectal cancer. These can be resected so as to decrease the
      morbidity and mortality rates. Colonoscopy is the gold-standard procedure for
      diagnosing and resecting precursor lesions. OBJECTIVE: To evaluate the
      epidemiological, endoscopic and histological aspects of endoscopic resection of
      lesions of the colon and rectum at a training center. MATERIALS AND METHOD: A
      search was conducted in the database of our institution covering the period from
      January 2011 to July 2014. Cases that underwent endoscopic resection of polyps
      and/or colorectal lesions were selection. The following variables were defined:
      general data on the patients (age, gender and indication from the examination)
      and data on the polypoid lesion (number, histological type and topographic
      distribution). RESULTS: 678 lesions were identified in 456 examinations.
      Regarding sex, 242 (53.1%) were female and 214 (46.9%) were male. The mean age
      was 64.54 years, with extremes of 5 and 94 years. The most frequent locations
      were the rectum (21%) and sigmoid (20%). Histologically, 34.7% were hyperplastic
      polyps and 58.9% were adenomatous polyps, of which 74.1% were tubular, 10.6%
      tubulovillous, 2% villous and 13% indeterminate; and 1.7% were adenocarcinomas.
      In 65.4% of the cases, the examination showed that only one polyps was present,
      while 34.6% had two or more lesions. CONCLUSION: In our clinic, with a mean of
      250 examinations/month, the parameters evaluated were compatible with the results
      reported in the literature.

PMID- 28489837
TI  - [Validation of the rapid urease test for the detection of Helicobacter pylori in
      a Peruvian hospital].
AB  - OBJECTIVE: To validate a rapid urease test (RUT) in Cayetano Heredia Hospital
      (HCH) in Lima, Peru. MATERIALS AND METHODS: This is a prospective observational
      study that included 181 patients over 18 years old with dyspeptic symptoms. All
      of them underwent upper gastrointestinal endoscopy at the Department of
      Gastroenterology at HCH. They had not received, during the last four weeks,
      proton pump inhibitors (PPIs), bismuth or antibiotics. Two biopsies of antrum
      were taken, one to perform the TRU (Sensibacter pylori test(r)) and the other one
      for pathology, in order to determine by both methods the presence of H. pylori
      infection. TRU's results were compared with pathology s (gold standard). RESULTS:
      181 patients, average age 52.8+/-13.5 years, were evaluated. The sensitivity,
      specificity, negative predictive value (NPV), positive predictive value (PPV) at
      20 minutes were 86.8%, 98.5%, 81.5% and 99% and at 24 hours 97.3%, 99.5%, 95.7% y
      99.1% respectively. CONCLUSION: The rapid urease test is a reliable, accessible
      and easy to apply test for the diagnosis of H. pylori infection.

PMID- 28489839
TI  - [Deregulation of microRNAs in gastric cancer: up regulation by miR-21 and miR
      106].
AB  - Gastric cancer (GC) exhibits significant rates of mortality worldwide, a
      situation that is even more disturbing in Colombia, because it has had
      historically high rate for that disease; At regional context we have found that
      Boyaca has the second place of gastric cancer mortality rate in the country, with
      displeasing numbers. Early detection is critical to the survival of people, so in
      this article, major based on world literature search, we show that the microRNA
      could be a useful tool for the diagnosis, prognosis and can be designed as
      important therapeutic target. Aims to this are demonstrate howmiRNAs are
      deregulated during the emergence and development of gastric cancer and how their
      biological functions can place them as oncogenes or tumor suppressors; finally,
      we showed that two microRNAs (miR-21 and miR-106b) are significantly upregulated
      in the disease and may have a pro-oncogenic action, blocking normal cell cycle,
      apoptosis and migration.

PMID- 28489838
TI  - [Diagnostic and therapeutic approach to small bowel disorders through capsule
      endoscopy and double-balloon endoscopy].
AB  - Many small bowel disorders represent a great challenge for gastroenterologists
      and endoscopists due to the very low rates of success showed by the different
      agnosis techniques. The advent of the capsule endoscopy and double-balloon
      endoscopy has allowed a total, secure and efficient examination of the small
      bowel, which represents a real impact in diagnosis, treatment, and prognosis of
      our patients. The capsule endoscopy is a safe, minimally invasive procedure,
      which does not need sedation, does not cause pain, and allows the observation of
      the totality of the small bowel. Furthermore, the double-balloon endoscopy is the
      complementary technique necessary to provide a therapeutic procedure (cauterizing
      angiodysplasia, polypectomy, biopsies), and hence achieving resolution of various
      disorders.

PMID- 28489840
TI  - [Pancreaticoduodenectomy for a solid pseudopapillary tumor of the pancreas in
      children].
AB  - The solid pseudopapillary tumor of the pancreas (SPT) is a rare neoplasm with low
      malignant potential in children. We report the case of a 9 years old child with a
      SPT localized in the pancreatic head. She underwent a pancreaticoduodenectomy
      (PD) with favorable evolution. The PD in high-volume centers is safe in both
      adults and children.

PMID- 28489841
TI  - [Colon Paracoccidioidomycosis in a hospital from Lima - Peru: report of 4 cases].
AB  - Paracoccidioidomycosis is the most prevalent mycosis in South America.
      Mucocutaneous and lymph node involvement is the most frequent affectation of this
      disease in our country, with the intestinal commitment rarely reported. We report
      4 cases of colonic manifestation with abdominal pain, chronic diarrhea, and
      weight loss. The diagnosis was made with biopsy and Gomori stain. The average age
      was 29 years old. The colonoscopy showed many ulcers in the ileum distal and
      colon. We found VIH as comorbidity in one patient.

PMID- 28489842
TI  - [Gastrointestinal bleeding in newborn with hookworm, National Hospital San
      Bartolome. Case report].
AB  - We present the case of gastrointestinal bleeding uncinariasis in a newborn baby
      of 27 days old from anindigenous town of Tangoshiri, located in the province of
      La Convencion, department of Cuzco, who enters to the service of neonatology
      National Teaching Hospital San Bartolome in Lima, Peru, with decompensated severe
      anemia. The baby has melena since the fourth day of his birth, which increased in
      the third week of life, with hematocrit of 12%. She was hospitalized, receiving
      blood transfusion and she continue with gastrointestinal bleeding, so she
      underwent an upper endoscopy that showed multiple larvae Ancylostoma duodenale.
      She and her mother were treated with mebendazole. Afterwords they had stool
      examinations without the presence of the parasite.

PMID- 28489843
TI  - [Non-cirrhotic portal hypertension due to didanosina. A rare case].
AB  - Liver involvement is usually seen in patients infected with the human
      immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B
      or C, in alcohol abuse, etc. However, there is a group of patients who develop
      liver involvement and portal hypertension of unspecified cause. Non-cirrhotic
      portal hypertension (NCPH) is a liver disorder recently described, but
      potentially serious. It has been reported in HIV-infected patients with highly
      active antiretroviral therapy (HAART), specifically didanosine (DDI). The
      pathophysiology involves the infectious agent (HIV) and its treatment (HAART),
      since both generate a pre-hepatic portal venulopathy. Similarly, HIV infection
      produces a prothrombotic state by protein S deficiency leading to the
      obliteration of small hepatic venules. It has been postulated that DDI as a
      cofactor in the pathogenesis of NCPH. All this leads that many of the liver
      biopsies show nodular regenerative hyperplasia. We present the case of a HIV
      infected patient who was treated with a longstanding DDI. She developed upper
      gastrointestinal bleeding (UGB) and ascites due to NCPH, whose diagnosis was
      confirmed by biopsy. However, there is no similar study in our country.

PMID- 28489844
TI  - Penetrating gastric ulcer as a manifestation of multisystemic tuberculosis.
AB  - We present the case of a 30-year old female with a history of abdominal pain,
      fever, poor oral tolerance and weight loss for 6 months. An abdominal CT scan
      showed marked gastric dilatation due to extrinsic compression from
      lymphadenopathies around the second portion of the duodenum. The upper endoscopy
      revealed the presence of a penetrating gastric ulcer in the greater curvature.
      Biopsies of the lesions showed hystiocytes with granulomatous features and Acid
      Fast Bacilli (AFB) positive, and the cultures grew Mycobacterium tuberculosis
      sensitive to Isonazid and Rifampin. Subsequently anti-TB regimen was initiated
      achieving great clinical and endoscopic improvement.

PMID- 28489845
TI  - Caput Medusae due to portal hypertension in schistosomiasis mansoni.
AB  - A 62-year-old Brazilian man who lived in endemic areas of tropical diseases had
      an episode of hematemesis associated with portal hypertension. He used to swim in
      natural ponds during childhood and developed the hepatosplenic form of
      schistossomiasis with moderate ascites, in addition to the characteristic
      features of abdominal Caput Medusae. The aim of the report is highlight the role
      of chronic liver disease and schistossomiasis.

PMID- 28489846
TI  - [Gastrointestinal bleeding and acute hepatic failure by leptospirosis: an entity
      that should not be forgotten].
AB  - Leptospirosis disease is caused by the spirochete Leptospira. It is a worldwide
      distribution zoonosis, with predominance in the tropics. In Spain, it is not
      frequent but some cases have been noticed especially in humid areas surrounded by
      rivers, lakes or ponds, such as Catalonia, Andalucia or the Valencian Community.
      It is transmitted by a variety of animals such as cows or rats, that are infected
      either by direct contact with these animals or their urine, or indirectly by
      consuming or being in contact with water contaminated by their urine. The
      clinical manifestations are very variable, being asymptomatic or not very
      symptomatic in most of the patients. Unusually, leptospirosis presents with a
      first phase with fever, myalgias, liver injury or different organs hemorrhage,
      followed by a second phase with the presence of jaundice due to hepatic failure.
      Weil's disease is a kind of severe leptospirosis characterized by hepatic failure
      with jaundice and acute renal failure, associated with high mortality rates.The
      diagnosis is based on serological techniques and DNA detection by PCR. The
      treatment consists of life support measures and antibiotic therapy. A patient
      with Weil's disease and leptospirosis digestive bleeding is presented, with a
      fulminant clinical course. In order to achieve an early diagnosis, the need to
      keep this entity in mind must be emphasized, especially in favorable
      epidemiological environments as the one of this patient.

PMID- 28489847
TI  - [Zinc in the management of diarrhea: adequate for all the pediatric population?]

PMID- 28489848
TI  - A coordinated DNA damage response promotes adult quiescent neural stem cell
      activation.
AB  - Stem and differentiated cells frequently differ in their response to DNA damage,
      which can determine tissue sensitivity. By exploiting insight into the spatial
      arrangement of subdomains within the adult neural subventricular zone (SVZ) in
      vivo, we show distinct responses to ionising radiation (IR) between neural stem
      and progenitor cells. Further, we reveal different DNA damage responses between
      neonatal and adult neural stem cells (NSCs). Neural progenitors (transit
      amplifying cells and neuroblasts) but not NSCs (quiescent and activated) undergo
      apoptosis after 2 Gy IR. This response is cell type- rather than proliferation
      dependent and does not appear to be driven by distinctions in DNA damage
      induction or repair capacity. Moreover, exposure to 2 Gy IR promotes
      proliferation arrest and differentiation in the adult SVZ. These 3 responses are
      ataxia telangiectasia mutated (ATM)-dependent and promote quiescent NSC (qNSC)
      activation, which does not occur in the subdomains that lack progenitors.
      Neuroblasts arising post-IR derive from activated qNSCs rather than irradiated
      progenitors, minimising damage compounded by replication or mitosis. We propose
      that rather than conferring sensitive cell death, apoptosis is a form of rapid
      cell death that serves to remove damaged progenitors and promote qNSC activation.
      Significantly, analysis of the neonatal (P5) SVZ reveals that although
      progenitors remain sensitive to apoptosis, they fail to efficiently arrest
      proliferation. Consequently, their repopulation occurs rapidly from irradiated
      progenitors rather than via qNSC activation.

PMID- 28489849
TI  - Utilizing BMP-2 muteins for treatment of multiple myeloma.
AB  - Multiple myeloma (MM) represents a haematological cancer characterized by the
      pathological hyper proliferation of antibody-producing B-lymphocytes. Patients
      typically suffer from kidney malfunction and skeletal disorders. In the context
      of MM, the transforming growth factor beta (TGFbeta) member Activin A was
      recently identified as a promoter of both accompanying symptoms. Because studies
      have shown that bone morphogenetic protein (BMP)-2-mediated activities are
      counteracted by Activin A, we analysed whether BMP2, which also binds to the
      Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8
      pathway, can be used to antagonize Activin A activities, such as in the context
      of MM. Therefore three BMP2 derivatives were generated with modified binding
      activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing
      either increased or decreased BMP2 activity. In the context of MM these BMP2
      muteins show two functionalities since they act as a) an anti
      proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation
      promoting growth factor. The molecular basis of both activities was shown in two
      different cellular models to clearly rely on the properties of the investigated
      BMP2 muteins to compete for the binding of Activin A to the Activin type II
      receptors. The experimental outcome suggests new therapeutic strategies using
      BMP2 variants in the treatment of MM-related pathologies.

PMID- 28489850
TI  - Testing the effect of the Himalayan mountains as a physical barrier to gene flow
      in Hippophae tibetana Schlect. (Elaeagnaceae).
AB  - Hippophae tibetana is a small, dioecious wind-pollinated shrub endemic to the
      Tibetan-Qinghai Plateau. It is one of the shrubs that occur at very high
      elevations (5250 m a.s.l.). The Himalayan mountains provides a significant
      geographical barrier to the Qinghai-Tibetan Plateau, dividing the Himalayan area
      into two regions with Nepal to the south and Tibet to the north. There is no
      information on how the Himalayan mountains influence gene flow and population
      differentiation of alpine plants. In this study, we analyzed eight nuclear
      microsatellite markers and cpDNA trnT-trnF regions to test the role of the
      Himalayan mountains as a barrier to gene flow between populations of H. tibetana.
      We also examined the fine-scale genetic structure within a population of H.
      tibetana on the north slope of Mount (Mt.) Everest. For microsatellite analyses,
      a total of 241 individuals were sampled from seven populations in our study area
      (4 from Nepal, 3 from Tibet), including 121 individuals that were spatially
      mapped within a 100 m * 100 m plot. To test for seed flow, the cpDNA trnT-trnF
      regions of 100 individuals from 6 populations (4 from Nepal, 2 from Tibet) were
      also sequenced. Significant genetic differentiation was detected between the two
      regions by both microsatellite and cpDNA data analyses. These two datasets agree
      about southern and northern population differentiation, indicating that the
      Himalayan mountains represent a barrier to H. tibetana limiting gene flow between
      these two areas. At a fine scale, spatial autocorrelation analysis suggests
      significant genetic structure within a distance of less than 45 m, which may be
      attributed mainly to vegetative reproduction and habitat fragmentation, as well
      as limited gene flow.

PMID- 28489852
TI  - Recurrent promoter mutations in melanoma are defined by an extended context
      specific mutational signature.
AB  - Sequencing of whole tumor genomes holds the promise of revealing functional
      somatic regulatory mutations, such as those described in the TERT promoter.
      Recurrent promoter mutations have been identified in many additional genes and
      appear to be particularly common in melanoma, but convincing functional data such
      as influence on gene expression has been more elusive. Here, we show that
      frequently recurring promoter mutations in melanoma occur almost exclusively at
      cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable
      exception. In active, but not inactive, promoters, mutation frequencies for
      cytosines at the 5' end of this ETS-like motif were considerably higher than
      expected based on a UV trinucleotide mutational signature. Additional analyses
      solidify this pattern as an extended context-specific mutational signature that
      mediates an exceptional position-specific vulnerability to UV mutagenesis,
      arguing against positive selection. We further use ultra-sensitive amplicon
      sequencing to demonstrate that cell cultures exposed to UV light quickly develop
      subclonal mutations specifically in affected positions. Our findings have
      implications for the interpretation of somatic mutations in regulatory regions,
      and underscore the importance of genomic context and extended sequence patterns
      to accurately describe mutational signatures in cancer.

PMID- 28489851
TI  - Global analysis of double-strand break processing reveals in vivo properties of
      the helicase-nuclease complex AddAB.
AB  - In bacteria, double-strand break (DSB) repair via homologous recombination is
      thought to be initiated through the bi-directional degradation and resection of
      DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has
      been well-studied in vitro, with translocation speeds between 400-2000 bp/s on
      linear DNA suggesting that a large section of DNA around a break site is
      processed for repair. However, the translocation rate and activity of AddAB in
      vivo is not known, and how AddAB is regulated to prevent excessive DNA
      degradation around a break site is unclear. To examine the functions and
      mechanistic regulation of AddAB inside bacterial cells, we developed a next
      generation sequencing-based approach to assay DNA processing after a site
      specific DSB was introduced on the chromosome of Caulobacter crescentus. Using
      this assay we determined the in vivo rates of DSB processing by AddAB and found
      that putative chi sites attenuate processing in a RecA-dependent manner. This
      RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a
      break site, limiting the effects of DSB processing on transcription. In sum, our
      results, taken together with prior studies, support a mechanism for regulating
      AddAB that couples two key events of DSB repair-the attenuation of DNA-end
      processing and the initiation of homology search by RecA-thereby helping to
      ensure that genomic integrity is maintained during DSB repair.

PMID- 28489853
TI  - Novel genes involved in severe early-onset obesity revealed by rare copy number
      and sequence variants.
AB  - Obesity is a multifactorial disorder with high heritability (50-75%), which is
      probably higher in early-onset and severe cases. Although rare monogenic forms
      and several genes and regions of susceptibility, including copy number variants
      (CNVs), have been described, the genetic causes underlying the disease still
      remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes
      and present in <1/2000 population controls) in 157 Spanish children with non
      syndromic early-onset obesity (EOO: body mass index >3 standard deviations above
      the mean at <3 years of age) using SNP array molecular karyotypes. We then
      performed case control studies (480 EOO cases/480 non-obese controls) with the
      validated CNVs and rare sequence variants (RSVs) detected by targeted
      resequencing of selected CNV genes (n = 14), and also studied the inheritance
      patterns in available first-degree relatives. A higher burden of gain-type CNVs
      was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In
      addition to a gain of the NPY gene in a familial case with EOO and attention
      deficit hyperactivity disorder, likely pathogenic CNVs included gains of
      glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor
      (GRPR), all inherited from obese parents. Putatively functional RSVs absent in
      controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with
      a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and
      SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a
      recessive model. The genes identified showed a clear enrichment of shared co
      expression partners with known genes strongly related to obesity, reinforcing
      their role in the pathophysiology of the disease. Our data reveal a higher burden
      of rare CNVs and RSVs in several related genes in patients with EOO compared to
      controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly
      penetrant forms of familial obesity.

PMID- 28489854
TI  - Functional and phenotypic evaluation of eosinophils from patients with the acute
      form of paracoccidioidomycosis.
AB  - BACKGROUND: Eosinophilia is a typical finding of the acute/juvenile form of
      paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This
      clinical form is characterized by depressed cellular immune response and
      production of Th2 cytokines. Moreover, it has been shown that the increased
      number of eosinophils in peripheral blood of patients returns to normal values
      after antifungal treatment. However, the role of eosinophils in PCM has never
      been evaluated. This study aimed to assess the phenotypic and functional
      characteristics of eosinophils in PCM. METHODS/PRINCIPAL FINDINGS: In 15 patients
      with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES)
      and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were
      higher levels of chemokines and granule proteins in the peripheral blood of
      patients compared to controls. Isolation of eosinophils from blood revealed a
      higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls,
      and a lower population of CD80+ cells. We also evaluated the fungicidal capacity
      of eosinophils in vitro. Our results revealed that eosinophils from PCM patients
      and controls exhibit similar ability to kill P. brasiliensis yeast cells,
      although eosinophils of patients were less responsive to IL-5 stimulation than
      controls. CONCLUSION/PRINCIPAL FINDINGS: In conclusion, we suggest that
      eosinophils might play a role in the host response to fungi and in the
      pathophysiology of PCM by inducing an intense and systemic inflammatory response
      in the initial phase of the infection.

PMID- 28489855
TI  - Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies
      and fomites in villages of Papua New Guinea.
AB  - BACKGROUND: Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major
      causes of leg ulcers in children in Africa and the Pacific Region. We
      investigated the presence of DNA (PCR positivity) from these bacteria on
      asymptomatic people, flies, and household linens in an endemic setting.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional study in rural
      villages of Lihir Island, Papua New Guinea during a yaws elimination campaign.
      Participants were asymptomatic subjects recruited from households with cases of
      leg ulcers, and from households without cases of leg ulcers. We rubbed swabs on
      the intact skin of the leg of asymptomatic individuals, and collected flies and
      swabs of environmental surfaces. All specimens were tested by PCR for H. ducreyi
      and T. p. pertenue DNA. Of 78 asymptomatic participants that had an adequate
      specimen for DNA detection, H. ducreyi-PCR positivity was identified in 16 (21%)
      and T. p. pertenue-PCR positivity in 1 (1%). In subgroup analyses, H. ducreyi-PCR
      positivity did not differ in participants exposed or not exposed to a case of H.
      ducreyi ulcer in the household (24% vs 18%; p = 0.76). Of 17 cultures obtained
      from asymptomatic participants, 2 (12%) yielded a definitive diagnosis of H.
      ducreyi, proving skin colonization. Of 10 flies tested, 9 (90%) had H. ducreyi
      DNA and 5 (50%) had T. p. pertenue DNA. Of 6 bed sheets sampled, 2 (33%) had H.
      ducreyi DNA and 1 (17%) had T. p. pertenue DNA. CONCLUSIONS/SIGNIFICANCE: This is
      the first time that H. ducreyi DNA and colonization has been demonstrated on the
      skin of asymptomatic children and that H. ducreyi DNA and T. p. pertenue DNA has
      been identified in flies and on fomites. The ubiquity of H. ducreyi in the
      environment is a contributing factor to the spread of the organism.

PMID- 28489856
TI  - Randomized trial of stopping or continuing ART among postpartum women with pre
      ART CD4 >= 400 cells/mm3.
AB  - BACKGROUND: Health benefits of postpartum antiretroviral therapy (ART) for human
      immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been
      assessed in randomized trials. METHODS: Asymptomatic, HIV-positive, non
      breastfeeding women with pre-ART CD4+ T-cell counts >= 400 cells/mm3 started on
      ART during pregnancy were randomized up to 42 days after delivery to continue or
      discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the
      preferred ART regimen. The sample size was selected to provide 88% power to
      detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc
      analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2
      and 3 events. All analyses were intent to treat. RESULTS: 1652 women from 52
      sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US
      were enrolled (1/2010-11/2014). Median age was 28 years and major racial
      categories were Black African (28%), Asian (25%) White (15%). Median entry CD4
      count was 696 cells/mm3 (IQR 575-869), median ART exposure prior to delivery was
      19 weeks (IQR 13-24) and 94% had entry HIV-1 RNA < 1000 copies/ml. After a median
      follow-up of 2.3 years, the primary composite endpoint rate was significantly
      lower than expected, and not significantly different between arms (continue arm
      0.21 /100 person years(py); discontinue 0.31/100 py, Hazard ratio (HR) 0.68, 95%
      CI: 0.19, 2.40). WHO Stage 2 and 3 events were significantly reduced with
      continued ART (2.08/100 py vs. 4.36/100 py in the discontinue arm; HR 0.48,
      95%CI: 0.33, 0.70). Toxicity rates did not differ significantly between arms.
      Among women randomized to continue ART, 189/827 (23%) had virologic failure; of
      the 155 with resistance testing, 103 (66%) failed without resistance to their
      current regimen, suggesting non-adherence. CONCLUSIONS: Overall, serious clinical
      events were rare among young HIV-positive post-partum women with high CD4 cell
      counts. Continued ART was safe and was associated with a halving of the rate of
      WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent
      need to improve adherence in this population. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00955968.

PMID- 28489858
TI  - Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded
      volume.
AB  - Molecular dynamics simulations are used to explore the effects of chaperonin-like
      cages on knotted proteins with very low sequence similarity, different depths of
      a knot but with a similar fold, and the same type of topology. The investigated
      proteins are VirC2, DndE and MJ0366 with two depths of a knot. A comprehensive
      picture how encapsulation influences folding rates is provided based on the
      analysis of different cage sizes and temperature conditions. Neither of these two
      effects with regard to knotted proteins has been studied by means of molecular
      dynamics simulations with coarse-grained structure-based models before. We show
      that encapsulation in a chaperonin is sufficient to self-tie and untie small
      knotted proteins (VirC2, DndE), for which the equilibrium process is not
      accessible in the bulk solvent. Furthermore, we find that encapsulation reduces
      backtracking that arises from the destabilisation of nucleation sites, smoothing
      the free energy landscape. However, this effect can also be coupled with
      temperature rise. Encapsulation facilitates knotting at the early stage of
      folding and can enhance an alternative folding route. Comparison to unknotted
      proteins with the same fold shows directly how encapsulation influences the free
      energy landscape. In addition, we find that as the size of the cage decreases,
      folding times increase almost exponentially in a certain range of cage sizes, in
      accordance with confinement theory and experimental data for unknotted proteins.

PMID- 28489857
TI  - Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in
      healthy adults.
AB  - INTRODUCTION: Vitamin D insufficiency, defined as 25-hydroxyvitamin D (25(OH)D)
      levels < 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D
      insufficiency is associated with inflammation and fibrosis, but it remains
      uncertain whether these anomalies are readily reversible. Therefore, we aimed to
      determine the effects of vitamin D supplementation on markers of: 1) nitric oxide
      (NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild
      hypovitaminosis. METHODS: Healthy volunteers (n = 35) (mean age: 45 +/- 11 years)
      with 25(OH)D levels <75nmol/L, received vitamin D supplementation (Ostelin (r)
      capsules 2000IU) for 12 weeks. Resting systolic and diastolic blood pressures
      (BP) were assessed. Routine biochemistry was examined. Plasma concentrations of
      asymmetric dimethylarginine (ADMA), thrombospondin-1 (TSP-1), plasminogen
      activator inhibitor-1 (PAI-1), hs-CRP, activin-A, and follistatin-like 3 (FSTL3)
      were quantitated. RESULTS: Vitamin D administration for 12 weeks significantly
      increased 25-(OH)D levels (48.8 +/- 16 nmol/L to 100.8 +/- 23.7 nmol/L, p<0.001).
      There was significant lowering of systolic and diastolic BP, while there was no
      significant change in lipid profiles, or fasting insulin. Plasma concentrations
      of ADMA, hs-CRP, PAI-1, activin A, and FSTL-3 did not change with vitamin D
      supplementation. However, there was a marked reduction of TSP-1 (522.7 +/- 379.8
      ng/mL vs 206.7 +/- 204.5 ng/mL, p<0.001). CONCLUSIONS: Vitamin D supplementation
      in vitamin D insufficient, but otherwise healthy individuals markedly decreased
      TSP-1 levels and blood pressure. Since TSP-1 suppresses signaling of NO, it is
      possible that the fall in BP is engendered by restoration of NO effect.

PMID- 28489859
TI  - An R2R3-type MYB transcription factor, GmMYB29, regulates isoflavone biosynthesis
      in soybean.
AB  - Isoflavones comprise a group of secondary metabolites produced almost exclusively
      by plants in the legume family, including soybean [Glycine max (L.) Merr.]. They
      play vital roles in plant defense and have many beneficial effects on human
      health. Isoflavone content is a complex quantitative trait controlled by multiple
      genes, and the genetic mechanisms underlying isoflavone biosynthesis remain
      largely unknown. Via a genome-wide association study (GWAS), we identified 28
      single nucleotide polymorphisms (SNPs) that are significantly associated with
      isoflavone concentrations in soybean. One of these 28 SNPs was located in the 5'
      untranslated region (5'-UTR) of an R2R3-type MYB transcription factor, GmMYB29,
      and this gene was thus selected as a candidate gene for further analyses. A
      subcellular localization study confirmed that GmMYB29 was located in the nucleus.
      Transient reporter gene assays demonstrated that GmMYB29 activated the IFS2
      (isoflavone synthase 2) and CHS8 (chalcone synthase 8) gene promoters.
      Overexpression and RNAi-mediated silencing of GmMYB29 in soybean hairy roots
      resulted in increased and decreased isoflavone content, respectively. Moreover, a
      candidate-gene association analysis revealed that 11 natural GmMYB29
      polymorphisms were significantly associated with isoflavone contents, and
      regulation of GmMYB29 expression could partially contribute to the observed
      phenotypic variation. Taken together, these results provide important genetic
      insights into the molecular mechanisms underlying isoflavone biosynthesis in
      soybean.

PMID- 28489860
TI  - Rediscovery of the enigmatic fungus-farming ant "Mycetosoritis" asper Mayr
      (Hymenoptera: Formicidae): Implications for taxonomy, phylogeny, and the
      evolution of agriculture in ants.
AB  - We report the rediscovery of the exceedingly rarely collected and enigmatic
      fungus-farming ant species Mycetosoritis asper. Since the description of the type
      specimen in 1887, only four additional specimens are known to have been added to
      the world's insect collections. Its biology is entirely unknown and its
      phylogenetic position within the fungus-farming ants has remained puzzling due to
      its aberrant morphology. In 2014 we excavated and collected twenty-one colonies
      of M. asper in the Floresta Nacional de Chapeco in Santa Catarina, Brazil. We
      describe here for the first time the male and larva of the species and complement
      the previous descriptions of both the queen and the worker. We describe, also for
      the first time, M. asper biology, nest architecture, and colony demographics, and
      identify its fungal cultivar. Molecular phylogenetic analyses indicate that both
      M. asper and M. clorindae are members of the genus Cyphomyrmex, which we show to
      be paraphyletic as currently defined. More precisely, M. asper is a member of the
      Cyphomyrmex strigatus group, which we also show to be paraphyletic with respect
      to the genus Mycetophylax. Based on these results, and in the interest of
      taxonomic stability, we transfer the species M. asper, M. clorindae, and all
      members of the C. strigatus group to the genus Mycetophylax, the oldest available
      name for this clade. Based on ITS sequence data, Mycetophylax asper practices
      lower agriculture, cultivating a fungal species that belongs to lower-attine
      fungal Clade 2, subclade F.

PMID- 28489861
TI  - Prognostic value of lncRNA SOX2OT for Chinese cancer patients: A meta-analysis.
AB  - SOX2OT has been demonstrated to be aberrantly expressed in several types of
      cancer and maybe serve as a prognostic marker for cancer patients. However, most
      individual studies have been limited by small sample sizes and controversial
      results. Therefore, the present meta-analysis was conducted to analyze available
      data to reveal the potential clinical application of SOX2OT on cancer prognosis,
      tumor progression, distance metastasis and lymph node metastasis. Up to February
      20, 2017, literature collections were conducted by comprehensive searching
      electronic databases, including Cochrane Library, PubMed, Embase, BioMed Central,
      Springer, ScienceDirect, ISI Web of Knowledge, together with three Chinese
      databases: China National Knowledge Internet (CNKI), Weipu and Wanfang. The
      hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to
      assess the strength of the association. Five studies with a total of 481 cancer
      patients were included in the present meta-analysis. The results indicated that
      elevated SOX2OT significantly predicted unfavorable overall survival (OS) (HR =
      2.44, 95% CI: 1.75-3.39, P<0.0001) and tumor progression (III/IV vs. I/II: HR
      1.62, 95%CI: 1.30-2.02, P<0.0001), but failed to predict distant metastasis (HR:
      3.30, 95%CI: 0.74-14.61, P = 0.12) and lymph node metastasis (HR: 1.29, 95% CI:
      0.87-1.91, P = 0.21). The results revealed that SOX2OT expression level was an
      independent prognostic biomarker for OS and tumor progression in Chinese cancer
      patients.

PMID- 28489864
TI  - Personality in the cockroach Diploptera punctata: Evidence for stability across
      developmental stages despite age effects on boldness.
AB  - Despite a recent surge in the popularity of animal personality studies and their
      wide-ranging associations with various aspects of behavioural ecology, our
      understanding of the development of personality over ontogeny remains poorly
      understood. Stability over time is a central tenet of personality; ecological
      pressures experienced by an individual at different life stages may, however,
      vary considerably, which may have a significant effect on behavioural traits.
      Invertebrates often go through numerous discrete developmental stages and
      therefore provide a useful model for such research. Here we test for both
      differential consistency and age effects upon behavioural traits in the
      gregarious cockroach Diploptera punctata by testing the same behavioural traits
      in both juveniles and adults. In our sample, we find consistency in boldness,
      exploration and sociality within adults whilst only boldness was consistent in
      juveniles. Both boldness and exploration measures, representative of risk-taking
      behaviour, show significant consistency across discrete juvenile and adult
      stages. Age effects are, however, apparent in our data; juveniles are
      significantly bolder than adults, most likely due to differences in the
      ecological requirements of these life stages. Size also affects risk-taking
      behaviour since smaller adults are both bolder and more highly explorative.
      Whilst a behavioural syndrome linking boldness and exploration is evident in
      nymphs, this disappears by the adult stage, where links between other behavioural
      traits become apparent. Our results therefore indicate that differential
      consistency in personality can be maintained across life stages despite age
      effects on its magnitude, with links between some personality traits changing
      over ontogeny, demonstrating plasticity in behavioural syndromes.

PMID- 28489862
TI  - Novel genes associated with enhanced motility of Escherichia coli ST131.
AB  - Uropathogenic Escherichia coli (UPEC) is the cause of ~75% of all urinary tract
      infections (UTIs) and is increasingly associated with multidrug resistance. This
      includes UPEC strains from the recently emerged and globally disseminated
      sequence type 131 (ST131), which is now the dominant fluoroquinolone-resistant
      UPEC clone worldwide. Most ST131 strains are motile and produce H4-type flagella.
      Here, we applied a combination of saturated Tn5 mutagenesis and transposon
      directed insertion site sequencing (TraDIS) as a high throughput genetic screen
      and identified 30 genes associated with enhanced motility of the reference ST131
      strain EC958. This included 12 genes that repress motility of E. coli K-12, four
      of which (lrhA, ihfA, ydiV, lrp) were confirmed in EC958. Other genes represented
      novel factors that impact motility, and we focused our investigation on
      characterisation of the mprA, hemK and yjeA genes. Mutation of each of these
      genes in EC958 led to increased transcription of flagellar genes (flhD and fliC),
      increased expression of the FliC flagellin, enhanced flagella synthesis and a
      hyper-motile phenotype. Complementation restored all of these properties to wild
      type level. We also identified Tn5 insertions in several intergenic regions
      (IGRs) on the EC958 chromosome that were associated with enhanced motility; this
      included flhDC and EC958_1546. In both of these cases, the Tn5 insertions were
      associated with increased transcription of the downstream gene(s), which resulted
      in enhanced motility. The EC958_1546 gene encodes a phage protein with similarity
      to esterase/deacetylase enzymes involved in the hydrolysis of sialic acid
      derivatives found in human mucus. We showed that over-expression of EC958_1546
      led to enhanced motility of EC958 as well as the UPEC strains CFT073 and UTI89,
      demonstrating its activity affects the motility of different UPEC strains.
      Overall, this study has identified and characterised a number of novel factors
      associated with enhanced UPEC motility.

PMID- 28489863
TI  - Combining phylogenetic and demographic inferences to assess the origin of the
      genetic diversity in an isolated wolf population.
AB  - The survival of isolated small populations is threatened by both demographic and
      genetic factors. Large carnivores declined for centuries in most of Europe due to
      habitat changes, overhunting of their natural prey and direct persecution.
      However, the current rewilding trends are driving many carnivore populations to
      expand again, possibly reverting the erosion of their genetic diversity. In this
      study we reassessed the extent and origin of the genetic variation of the Italian
      wolf population, which is expanding after centuries of decline and isolation. We
      genotyped wolves from Italy and other nine populations at four mtDNA regions
      (control-region, ATP6, COIII and ND4) and 39 autosomal microsatellites. Results
      of phylogenetic analyses and assignment procedures confirmed in the Italian
      wolves a second private mtDNA haplotype, which belongs to a haplogroup
      distributed mostly in southern Europe. Coalescent analyses showed that the unique
      mtDNA haplotypes in the Italian wolves likely originated during the late
      Pleistocene. ABC simulations concordantly showed that the extant wolf populations
      in Italy and in south-western Europe started to be isolated and declined right
      after the last glacial maximum. Thus, the standing genetic variation in the
      Italian wolves principally results from the historical isolation south of the
      Alps.

PMID- 28489865
TI  - Awareness, treatment, and control of hypertension is low among adults in Aksum
      town, northern Ethiopia: A sequential quantitative-qualitative study.
AB  - INTRODUCTION: Hypertension is a major risk factor of cardiovascular diseases
      which are the leading causes of deaths from chronic non-communicable diseases in
      Ethiopia. However, little is documented in the issue. Therefore, this study aimed
      to assess the prevalence, associated factors, awareness, treatment and control of
      hypertension among adults 18 years old or above in Aksum town, Tigray region,
      North Ethiopia. METHODS: A sequential quantitative-qualitative study was
      conducted among adults aged 18 years and above in Aksum town. A multi stage
      sampling procedure was used to select the study participants for the quantitative
      study whilst convenience sampling technique was used for the qualitative part. A
      pre-tested and structured questionnaire was used to collect quantitative data,
      and an interview guide was used to collect the qualitative data. The logistic
      regression model was fitted to identify factors independently associated with
      hypertension using SPSS Version 20. P-values of < 0.05 were considered
      statistically significant. For the qualitative data, iterative hearing of the
      discussions verbatim interpretation was followed by categorizing similar ideas
      into themes and finally triangulated with the quantitative results. RESULTS: The
      overall prevalence of hypertension was 16.5% (95% CI: 13.4, 20.0). Awareness,
      treatment and control of hypertension were 43%, 2.1% and 18.2%, respectively.
      Being unable to read and write [AOR = 4.73, 95% CI:1.11, 20.23], not consuming
      fruit [AOR = 4.31, 95% CI:1.74, 10.66], being physically inactive [AOR = 20.11,
      95% CI:8.75, 6.20], not knowing physical inactivity is a risk factor of
      hypertension [AOR = 3.57, 95% CI: 1.69, 7.69] and being overweight/obese [AOR =
      9.2, 95% CI:4.54, 18.67] were significantly associated with hypertension.
      Remarkably, all identified hypertensive cases were linked to the nearby hospital
      for confirmation of diagnosis, care and follow-up and all of them were found to
      be hypertensive. This suggests that implementing primary health care approach
      integrated with the urban health extension package may be effective in the
      prevention and control of hypertension in poor settings. CONCLUSION AND
      RECOMMENDATION: Prevalence of hypertension among adults was very high, but
      awareness, treatment and control of hypertension was very low. Being unable to
      read and write, not consuming fruit, being physically inactive,
      overweight/obesity and not knowing physical inactivity is a risk factor for
      hypertension were independently associated with hypertension. Policy makers need
      to consider integrating prevention and control of hypertension with health
      extension package. Appropriate information, education and communication
      strategies should also be designed and implemented to avoid unhealthy lifestyles
      and promote healthy practices.

PMID- 28489866
TI  - Magmatic evolution of Panama Canal volcanic rocks: A record of arc processes and
      tectonic change.
AB  - Volcanic rocks along the Panama Canal present a world-class opportunity to
      examine the relationship between arc magmatism, tectonic forcing, wet and dry
      magmas, and volcanic structures. Major and trace element geochemistry of Canal
      volcanic rocks indicate a significant petrologic transition at 21-25 Ma.
      Oligocene Bas Obispo Fm. rocks have large negative Nb-Ta anomalies, low HREE,
      fluid mobile element enrichments, a THI of 0.88, and a H2Ocalc of >3 wt. %. In
      contrast, the Miocene Pedro Miguel and Late Basalt Fm. exhibit reduced Nb-Ta
      anomalies, flattened REE curves, depleted fluid mobile elements, a THI of 1.45, a
      H2Ocalc of <1 wt. %, and plot in mid-ocean ridge/back-arc basin fields.
      Geochemical modeling of Miocene rocks indicates 0.5-0.1 kbar crystallization
      depths of hot (1100-1190 degrees C) magmas in which most compositional diversity
      can be explained by fractional crystallization (F = 0.5). However, the most
      silicic lavas (Las Cascadas Fm.) require an additional mechanism, and
      assimilation-fractional-crystallization can reproduce observed compositions at
      reasonable melt fractions. The Canal volcanic rocks, therefore, change from
      hydrous basaltic pyroclastic deposits typical of mantle-wedge-derived magmas, to
      hot, dry bi-modal magmatism at the Oligocene-Miocene boundary. We suggest the
      primary reason for the change is onset of arc perpendicular extension localized
      to central Panama. High-resolution mapping along the Panama Canal has revealed a
      sequence of inward dipping maar-diatreme pyroclastic pipes, large basaltic sills,
      and bedded silicic ignimbrites and tuff deposits. These volcanic bodies intrude
      into the sedimentary Canal Basin and are cut by normal and subsequently strike
      slip faults. Such pyroclastic pipes and basaltic sills are most common in
      extensional arc and large igneous province environments. Overall, the change in
      volcanic edifice form and geochemistry are related to onset of arc perpendicular
      extension, and are consistent with the idea that Panama arc crust fractured
      during collision with South America forming the observed Canal extensional zone.

PMID- 28489867
TI  - A shape-based inter-layer contours correspondence method for ICT-based reverse
      engineering.
AB  - The correspondence of a stack of planar contours in ICT (industrial computed
      tomography)-based reverse engineering, a key step in surface reconstruction, is
      difficult when the contours or topology of the object are complex. Given the
      regularity of industrial parts and similarity of the inter-layer contours, a
      specialized shape-based inter-layer contours correspondence method for ICT-based
      reverse engineering was presented to solve the above problem based on the
      vectorized contours. In this paper, the vectorized contours extracted from the
      slices consist of three graphical primitives: circles, arcs and segments. First,
      the correspondence of the inter-layer primitives is conducted based on the
      characteristics of the primitives. Second, based on the corresponded primitives,
      the inter-layer contours correspond with each other using the proximity rules and
      exhaustive search. The proposed method can make full use of the shape information
      to handle industrial parts with complex structures. The feasibility and
      superiority of this method have been demonstrated via the related experiments.
      This method can play an instructive role in practice and provide a reference for
      the related research.

PMID- 28489868
TI  - Predicting and understanding law-making with word vectors and an ensemble model.
AB  - Out of nearly 70,000 bills introduced in the U.S. Congress from 2001 to 2015,
      only 2,513 were enacted. We developed a machine learning approach to forecasting
      the probability that any bill will become law. Starting in 2001 with the 107th
      Congress, we trained models on data from previous Congresses, predicted all bills
      in the current Congress, and repeated until the 113th Congress served as the
      test. For prediction we scored each sentence of a bill with a language model that
      embeds legislative vocabulary into a high-dimensional, semantic-laden vector
      space. This language representation enables our investigation into which words
      increase the probability of enactment for any topic. To test the relative
      importance of text and context, we compared the text model to a context-only
      model that uses variables such as whether the bill's sponsor is in the majority
      party. To test the effect of changes to bills after their introduction on our
      ability to predict their final outcome, we compared using the bill text and meta
      data available at the time of introduction with using the most recent data. At
      the time of introduction context-only predictions outperform text-only, and with
      the newest data text-only outperforms context-only. Combining text and context
      always performs best. We conducted a global sensitivity analysis on the combined
      model to determine important variables predicting enactment.

PMID- 28489869
TI  - Interaction between birds and macrofauna within food webs of six intertidal
      habitats of the Wadden Sea.
AB  - The determination of food web structures using Ecological Network Analysis (ENA)
      is a helpful tool to get insight into complex ecosystem processes. The intertidal
      area of the Wadden Sea is structured into diverse habitat types which differ in
      their ecological functioning. In the present study, six different intertidal
      habitats (i.e. cockle field, razor clam field, mud flat, mussel bank, sand flat
      and seagrass meadow) were analyzed using ENA to determine similarities and
      characteristic differences in the food web structure of the systems. All six
      systems were well balanced between their degree of organization and their
      robustness. However, they differed in their detailed features. The cockle field
      and the mussel bank exhibited a strong dependency on external imports. The razor
      clam field appeared to be a rather small system with low energy transfer. In the
      mud flat microphytobenthos was used as a main food source and the system appeared
      to be sensitive to perturbations. Bird predation was the most pronounced in the
      sand flat and the seagrass meadow and led to an increase in energy transfer and
      parallel trophic cycles in these habitats. Habitat diversity appears to be an
      important trait for the Wadden Sea as each subsystem seems to have a specific
      role in the overall functioning of the entire ecosystem.

PMID- 28489870
TI  - New gSSR and EST-SSR markers reveal high genetic diversity in the invasive plant
      Ambrosia artemisiifolia L. and can be transferred to other invasive Ambrosia
      species.
AB  - Ambrosia artemisiifolia L., (common ragweed), is an annual invasive and highly
      troublesome plant species originating from North America that has become
      widespread across Europe. New sets of genomic and expressed sequence tag (EST)
      based simple sequence repeats (SSRs) markers were developed in this species using
      three approaches. After validation, 13 genomic SSRs and 13 EST-SSRs were retained
      and used to characterize the genetic diversity and population genetic structure
      of Ambrosia artemisiifolia populations from the native (North America) and
      invasive (Europe) ranges of the species. Analysing the mating system based on
      maternal families did not reveal any departure from complete allogamy and excess
      homozygosity was mostly due the presence of null alleles. High genetic diversity
      and patterns of genetic structure in Europe suggest two main introduction events
      followed by secondary colonization events. Cross-species transferability of the
      newly developed markers to other invasive species of the Ambrosia genus was
      assessed. Sixty-five percent and 75% of markers, respectively, were transferable
      from A. artemisiifolia to Ambrosia psilostachya and Ambrosia tenuifolia. 40% were
      transferable to Ambrosia trifida, this latter species being seemingly more
      phylogenetically distantly related to A. artemisiifolia than the former two.

PMID- 28489871
TI  - Anatomy, taphonomy, and phylogenetic implications of a new specimen of Eolambia
      caroljonesa (Dinosauria: Ornithopoda) from the Cedar Mountain Formation, Utah,
      USA.
AB  - BACKGROUND: Eolambia caroljonesa is the most abundant dinosaur in the lower
      Cenomanian Mussentuchit Member of the Cedar Mountain Formation of Utah, and one
      of the most completely known non-hadrosaurid iguanodontians from North America.
      In addition to the large holotype and paratype partial skulls, copious remains of
      skeletally immature individuals, including three bonebeds, have been referred to
      E. caroljonesa. Nevertheless, aspects of the postcranial anatomy of this taxon,
      particularly the pelvic girdle, have remained ambiguous due to the lack of
      associated postcranial material of larger, more mature individuals.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a recently discovered associated
      partial postcranial skeleton of a large Eolambia caroljonesa. This specimen, FMNH
      PR 3847, provides new anatomical data regarding the vertebral column and pelvic
      girdle, supplementing previous diagnoses and descriptions of E. caroljonesa. A
      new phylogenetic analysis incorporating information from FMNH PR 3847 places E.
      caroljonesa as a basal hadrosauromorph closely related to Protohadros byrdi from
      the Cenomanian Woodbine Formation of Texas. Histological analysis of FMNH PR 3847
      reveals that it represents a subadult individual eight to nine years of age.
      Taphonomic analysis indicates that FMNH PR 3847 was preserved in a crevasse splay
      deposit, along with an unusual abundance of small crocodylomorph material.
      CONCLUSIONS/SIGNIFICANCE: FMNH PR 3847 provides a wealth of new morphological
      data, adding to the anatomical and systematic characterization of Eolambia
      caroljonesa, and histological data, revealing new information on growth history
      in a basal hadrosauromorph. Taphonomic characterization of FMNH PR 3847 and
      associated vertebrate material will allow comparison with other vertebrate
      localities in the Mussentuchit Member of the Cedar Mountain Formation.

PMID- 28489872
TI  - Gender differences in scientific collaborations: Women are more egalitarian than
      men.
AB  - By analyzing a unique dataset of more than 270,000 scientists, we discovered
      substantial gender differences in scientific collaborations. While men are more
      likely to collaborate with other men, women are more egalitarian. This is
      consistently observed over all fields and regardless of the number of
      collaborators a scientist has. The only exception is observed in the field of
      engineering, where this gender bias disappears with increasing number of
      collaborators. We also found that the distribution of the number of collaborators
      follows a truncated power law with a cut-off that is gender dependent and related
      to the gender differences in the number of published papers. Considering
      interdisciplinary research, our analysis shows that men and women behave
      similarly across fields, except in the case of natural sciences, where women with
      many collaborators are more likely to have collaborators from other fields.

PMID- 28489873
TI  - Identification of persistent benthic assemblages in areas with different
      temperature variability patterns through broad-scale mapping.
AB  - Ecosystem-based management is a place-based approach that considers the
      relationships between system parts. Due to the complexity of ecosystems in the
      marine environment it is often difficult to define these relationships in space
      and time. Maps illustrate spatial concepts. Here we promote ecosystem-based
      spatial thinking by layering datasets from a larger project that mapped benthic
      fauna, substrate characteristics, and oceanic conditions on monthly, annual and
      decadal time scales along the U.S. continental shelf. By combining maps of
      persistent benthic megafauna and bottom temperature variability over
      approximately 90,000 km2, we identified wide spread benthic animal assemblages
      and regional disparity in temperature variability. From a broad-scale perspective
      the locations of the assemblage appear to be related to sea scallop population
      dynamics and indicate potential regional differences in climate change
      resiliency. These findings offer information on a scale that correlates with
      marine spatial planning, and could be used as a starting point for further
      investigation. To spur additional analysis and facilitate their linkage to other
      datasets, these datasets are available through public, online data portals.
      Overall, this study demonstrates how the growth of maps from single to multiple
      elements can help promote and facilitate the multifactor, ecosystem-based
      thinking needed to support regional ocean planning.

PMID- 28489874
TI  - Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits
      apoptosis.
AB  - Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal
      cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer
      cells remains unknown. This study aims to explore the expression and function of
      TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein
      in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial
      lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by
      immunohistochemistry, the expression of TAZ protein gradually increased from NC
      to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells
      by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ.
      In vitro, the cell growth curves and MTT assays showed that TAZ may promote the
      growth and viability of cervical cancer cells. In vivo, xenografts experiment
      showed that TAZ may increase tumor-forming ability. The percentage of apoptosis
      cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits
      apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and
      Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken
      together, this study demonstrated that TAZ is overexpressed in cervical cancer
      and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

PMID- 28489875
TI  - Functional data analysis of sleeping energy expenditure.
AB  - Adequate sleep is crucial during childhood for metabolic health, and physical and
      cognitive development. Inadequate sleep can disrupt metabolic homeostasis and
      alter sleeping energy expenditure (SEE). Functional data analysis methods were
      applied to SEE data to elucidate the population structure of SEE and to
      discriminate SEE between obese and non-obese children. Minute-by-minute SEE in
      109 children, ages 5-18, was measured in room respiration calorimeters. A
      smoothing spline method was applied to the calorimetric data to extract the true
      smoothing function for each subject. Functional principal component analysis was
      used to capture the important modes of variation of the functional data and to
      identify differences in SEE patterns. Combinations of functional principal
      component analysis and classifier algorithm were used to classify SEE. Smoothing
      effectively removed instrumentation noise inherent in the room calorimeter data,
      providing more accurate data for analysis of the dynamics of SEE. SEE exhibited
      declining but subtly undulating patterns throughout the night. Mean SEE was
      markedly higher in obese than non-obese children, as expected due to their
      greater body mass. SEE was higher among the obese than non-obese children
      (p<0.01); however, the weight-adjusted mean SEE was not statistically different
      (p>0.1, after post hoc testing). Functional principal component scores for the
      first two components explained 77.8% of the variance in SEE and also differed
      between groups (p = 0.037). Logistic regression, support vector machine or random
      forest classification methods were able to distinguish weight-adjusted SEE
      between obese and non-obese participants with good classification rates (62-64%).
      Our results implicate other factors, yet to be uncovered, that affect the weight
      adjusted SEE of obese and non-obese children. Functional data analysis revealed
      differences in the structure of SEE between obese and non-obese children that may
      contribute to disruption of metabolic homeostasis.

PMID- 28489876
TI  - Socioeconomic inequalities in mortality, morbidity and diabetes management for
      adults with type 1 diabetes: A systematic review.
AB  - AIMS: To systematically review the evidence of socioeconomic inequalities for
      adults with type 1 diabetes in relation to mortality, morbidity and diabetes
      management. METHODS: We carried out a systematic search across six relevant
      databases and included all studies reporting associations between socioeconomic
      indicators and mortality, morbidity, or diabetes management for adults with type
      1 diabetes. Data extraction and quality assessment was undertaken for all
      included studies. A narrative synthesis was conducted. RESULTS: A total of 33
      studies were identified. Twelve cohort, 19 cross sectional and 2 case control
      studies met the inclusion criteria. Regardless of healthcare system, low
      socioeconomic status was associated with poorer outcomes. Following adjustments
      for other risk factors, socioeconomic status was a statistically significant
      independent predictor of mortality in 9/10 studies and morbidity in 8/10 studies
      for adults with type 1 diabetes. There appeared to be an association between low
      socioeconomic status and some aspects of diabetes management. Although only 3 of
      16 studies made adjustments for confounders and other risk factors, poor diabetes
      management was associated with lower socioeconomic status in 3/3 of these
      studies. CONCLUSIONS: Low socioeconomic status is associated with higher levels
      of mortality and morbidity for adults with type 1 diabetes even amongst those
      with access to a universal healthcare system. The association between low
      socioeconomic status and diabetes management requires further research given the
      paucity of evidence and the potential for diabetes management to mitigate the
      adverse effects of low socioeconomic status.

PMID- 28489877
TI  - Low back pain in healthy postmenopausal women and the effect of physical
      activity: A secondary analysis in a randomized trial.
AB  - Epidemiological studies on the prevalence of musculoskeletal pain have
      consistently shown that this is a relevant health problem, with non-specific low
      back pain (LBP) being the most commonly reported in adult females. Conflicting
      data on the association between LBP symptoms and physical activity (PA) have been
      reported. Here, we investigated the prevalence of LBP and the effect of a 24
      month non-specific PA intervention on changes in LBP prevalence in a series of
      Italian healthy postmenopausal women. We performed a secondary analysis in the
      frame of the DAMA trial, a factorial randomized intervention trial aimed to
      evaluate the ability of a 24-month intervention, based on moderate-intensity PA,
      and/or dietary modification, in reducing mammographic breast density in healthy
      postmenopausal women. The PA intervention included at least 1 hour/day of
      moderate PA and a more strenuous weekly activity, collective walks and
      theoretical group sessions. A self-administered pain questionnaire was
      administered at baseline and at the end of the intervention. The questionnaire
      was specifically structured to investigate the occurrence of musculoskeletal
      pain, the body localization, intensity and duration of the pain. Two hundred and
      ten women (102 randomized to PA intervention, 108 not receiving the PA
      intervention) filled out the questionnaires. At baseline LBP was present in 32.9%
      of the participants. Among women randomized to the PA intervention, LBP
      prevalence at follow up (21.6%) was lower than at baseline (33.3%) (p = 0.02),
      while in women who did not receive the PA intervention the LBP prevalence at
      baseline and follow up were 32.4% and 25.9%, respectively (p = 0.30). Overall,
      there was no significant between-group effect of PA intervention on LBP. Further
      studies are needed to understand the role of non-specific PA intervention, aimed
      to improve overall fitness, on LBP prevalence.

PMID- 28489878
TI  - Impact of life history traits on gene flow: A multispecies systematic review
      across oceanographic barriers in the Mediterranean Sea.
AB  - BACKGROUND: Marine species can demonstrate strong genetic differentiation and
      population structure despite the hypothesis of open seas and high connectivity.
      Some suggested drivers causing the genetic breaks are oceanographic barriers and
      the species' biology. We assessed the relevance of seven major oceanographic
      fronts on species connectivity while considering their dispersal capacity and
      life strategy. METHODS: We systematically reviewed the scientific articles
      reporting population genetic differentiation along the Mediterranean Sea and
      across the Atlantic-Mediterranean transition. We retained those considering at
      least one sampling locality at each side of an oceanographic front, and at least
      two localities with no-front between them to correctly assess the effect of the
      front. To estimate the impact of life history characteristics affecting
      connectivity we considered the planktonic larval duration (PLD) and adult life
      strategy. RESULTS: Oceanographic barriers in the Mediterranean Sea seem to reduce
      gene flow globally; however, this effect is not homogeneous considering the life
      history traits of the species. The effect of the oceanographic fronts reduces
      gene flow in highly mobile species with PLD larger than 2-4 weeks. Benthic
      sessile species and/or with short PLD (< 2 weeks) have more significant genetic
      breaks between localities than species with higher motility; however, genetic
      differentiation occurs independently of the presence of a front. CONCLUSION:
      Genetic connectivity is important for populations to recover from anthropogenic
      or natural impacts. We show that species with low mobility, mostly habitat
      formers, have high genetic differentiation but low gene flow reduction mediated
      by the front, therefore, considering the importance of these species, we
      emphasize the vulnerability of the Mediterranean ecosystems and the necessity of
      protection strategies based on the whole ecosystem.

PMID- 28489880
TI  - Carbon storage in the seagrass meadows of Gazi Bay, Kenya.
AB  - Vegetated marine habitats are globally important carbon sinks, making a
      significant contribution towards mitigating climate change, and they provide a
      wide range of other ecosystem services. However, large gaps in knowledge remain,
      particularly for seagrass meadows in Africa. The present study estimated biomass
      and sediment organic carbon (Corg) stocks of four dominant seagrass species in
      Gazi Bay, Kenya. It compared sediment Corg between seagrass areas in vegetated
      and un-vegetated 'controls', using the naturally patchy occurence of seagrass at
      this site to test the impacts of seagrass growth on sediment Corg. It also
      explored relationships between the sediment and above-ground Corg, as well as
      between the total biomass and above-ground parameters. Sediment Corg was
      significantly different between species, range: 160.7-233.8 Mg C ha-1 (compared
      to the global range of 115.3 to 829.2 Mg C ha-1). Vegetated areas in all species
      had significantly higher sediment Corg compared with un-vegetated controls; the
      presence of seagrass increased Corg by 4-6 times. Biomass carbon differed
      significantly between species with means ranging between 4.8-7.1 Mg C ha-1
      compared to the global range of 2.5-7.3 Mg C ha-1. To our knowledge, these are
      among the first results on seagrass sediment Corg to be reported from African
      seagrass beds; and contribute towards our understanding of the role of seagrass
      in global carbon dynamics.

PMID- 28489879
TI  - Lack of significant associations with early career performance suggest no link
      between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters.
AB  - The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and
      Norway mainly used for harness racing. Previous studies have shown that a
      mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related
      transcription factor 3 (DMRT3) gene has a major impact on harness racing
      performance of different breeds. An association of the DMRT3 mutation with early
      career performance has also been suggested. The aim of the current study was to
      investigate this proposed association in a randomly selected group of CBTs. 769
      CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The
      association with racing performance was investigated for 13 performance traits
      and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of
      age, using the statistical software R. Each performance trait was analyzed for
      association with DMRT3 using linear models. The results suggest no association of
      the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two
      traits (race time and number of disqualifications) were significantly different
      between the genotypes, with AA horses having the fastest times and CC horses
      having the highest number of disqualifications at 3 years of age. The frequency
      of the AA genotype was significantly lower in the raced CBT sample compared with
      the unraced sample and less than 50% of the AA horses participated in a race. For
      the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to
      demonstrate significantly better performance than the other genotypes. Although
      suggested as the most favorable genotype for racing performance in Standardbreds
      and Finnhorses across all ages, the AA genotype does not appear to be associated
      with superior performance, early or late, in the racing career of CBTs.

PMID- 28489881
TI  - Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells
      under hypoxic condition.
AB  - We tested the hypotheses that hypoxic stimulation enhances growth potentials of
      canine lymphoma cells by activating hypoxia-inducible factor 1alpha (HIF-1alpha),
      and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the
      cells. We investigated how hypoxic culture affects the growth rate,
      chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)
      resistant lymphoma cells, and influences of TH-302 on survival rate of the cells
      under hypoxic conditions. Our results demonstrated that hypoxic culture
      upregulated the expression of HIF-1alpha and its target genes, including ATP
      binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2
      (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth
      factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and
      invasiveness of the cells. Additionally, TH-302 decreased the survival rate of
      the cells under hypoxic condition. Our studies suggest that hypoxic stimulation
      may advance the tumorigenicity of canine lymphoma cells, favoring malignant
      transformation. Therefore, the data presented may contribute to the development
      of TH-302-based hypoxia-targeting therapies for canine lymphoma.

PMID- 28489882
TI  - Preparation of a novel antiserum to aromatase with high affinity and specificity:
      Its clinicopathological significance on breast cancer tissue.
AB  - Aromatase inhibitors have been widely used for the endocrine treatment of
      estrogen-dependent breast cancer in postmenopausal patients. However,
      clinicopathological studies of aromatase have been limited due to unsatisfactory
      specificity and/or restricted availability of anti-aromatase antibodies. Here, we
      have generated a polyclonal antiserum with high affinity and specificity for
      human aromatase using a monoclonal antibody tagged immunoaffinity chromatography
      on an industrial production scale. Our preliminary immunohistochemical analysis
      of 221 invasive breast cancer cases indicated that 87.3% (193/221) had at least
      5% aromatase positive cells. The histoscore for aromatase was inversely
      correlated with pT (p = 0.019), pN (p = 0.001), stage (p < 0.001), histologic
      grade (p = 0.003), lymphatic infiltration (p < 0.001), venous infiltration (p <
      0.001), and Ki-67 index (p < 0.001). However, cancer aromatase expression was
      independent of estrogen receptor (ER), progesterone receptor (PgR), and human
      epidermal growth factor receptor 2 statuses. This antiserum will be applicable to
      clinicopathological examination of aromatase in addition to ER and PgR for an
      appropriate use of aromatase inhibitor on the treatment of breast cancer. Further
      studies on the relationship between Aromatase inhibitors have been widely used
      for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal
      patients. However, clinicopathological studies of aromatase have been limited due
      to unsatisfactory specificity and/or restricted availability of anti-aromatase
      antibodies. Here, we have generated a polyclonal antiserum with high affinity and
      specificity for human aromatase using a monoclonal antibody tagged immunoaffinity
      chromatography on an industrial production scale. Our preliminary
      immunohistochemical analysis of 221 invasive breast cancer cases indicated that
      87.3% (193/221) had at least 5% aromatase positive cells. The histoscore for
      aromatase was inversely correlated with pT (p = 0.019), pN (p = 0.001), stage (p
      < 0.001), histologic grade (p = 0.003), lymphatic infiltration (p < 0.001),
      venous infiltration (p < 0.001), and Ki-67 index (p < 0.001). However, cancer
      aromatase expression was independent of estrogen receptor (ER), progesterone
      receptor (PgR), and human epidermal growth factor receptor 2 statuses. This
      antiserum will be applicable to clinicopathological examination of aromatase in
      addition to ER and PgR for an appropriate use of aromatase inhibitor on the
      treatment of breast cancer. Further studies on the relationship between aromatase
      expression and aromatase inhibitors are warranted.

PMID- 28489884
TI  - Comparison of the prognostic values of preoperative inflammation-based parameters
      in patients with breast cancer.
AB  - Peripheral blood-derived inflammation-based markers, including C-reactive protein
      (CRP), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR),
      and platelet-to-lymphocyte ratio (PLR) are indicators of prognosis in various
      malignant tumors. The present study aimed to identify the inflammation-based
      parameters that are most suitable for predicting outcomes in patients with breast
      cancer. Two hundred ninety-six patients who underwent surgery for localized
      breast cancer were reviewed retrospectively. The association between
      clinicopathological factors and inflammation-based parameters were investigated.
      Univariate and multivariate Cox regression analyses were performed to identify
      independent prognostic indicators associated with disease-free survival (DFS).
      The NLR level correlated significantly with tumor size (P<0.05). The PLR level
      correlated with the expression of estrogen receptor and lymph node involvement
      (P<0.05). Univariate analysis revealed that lower CRP and PLR values as well as
      tumor size, lymph node involvement, and nuclear grade were significantly
      associated with superior DFS (CRP: P<0.01; PLR, tumor size, lymph node
      involvement, and nuclear grade: P<0.05). On multivariate analysis, CRP (hazard
      ratio [HR]: 2.85, 95% confidence interval [CI]: 1.03-7.88, P<0.05), PLR (HR:
      2.61, 95% CI: 1.07-6.36, P<0.05) and nuclear grade (HR: 3.066, 95% CI: 1.26-7.49,
      P<0.05) were significant prognostic indicators of DFS in patients with breast
      cancer. Neither LMR nor NLR significantly predicted DFS. Both preoperative CRP
      and PLR values were independently associated with poor prognosis in patients with
      breast carcinoma; these were superior to other inflammation-based scores in terms
      of prognostic ability.

PMID- 28489883
TI  - BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF
      beta receptor type I ALK5.
AB  - Selection and maturation of B cells into plasma cells producing high-affinity
      antibodies occur in germinal centers (GC). GCs form transiently in secondary
      lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated
      process. TGF-beta is a potent negative regulator, but the influence of other
      family members including bone morphogenetic proteins (BMPs) is less known.
      Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed
      plasmablast differentiation, whereas BMP-7 induced apoptosis. Here, we show that
      human naive and GC B cells had a strikingly different receptor expression
      pattern. GC B cells expressed high levels of BMP type I receptor but low levels
      of type II receptors, whereas naive B cells had the opposite pattern.
      Furthermore, GC B cells had elevated levels of downstream signaling components
      SMAD1 and SMAD5, but reduced levels of the inhibitory SMAD7. Functional assays of
      GC B cells revealed that BMP-7 suppressed the viability-promoting effect of CD40L
      and IL-21, but had no effect on CD40L- and IL-21-induced differentiation into
      plasmablasts. BMP-7-induced apoptosis was counteracted by a selective TGF-beta
      type I receptor (ALK4/5/7) inhibitor, but not by a selective BMP receptor type I
      inhibitor. Furthermore, overexpression of truncated ALK5 in a B-cell line
      counteracted BMP-7-induced apoptosis, whereas overexpression of truncated ALK4
      had no effect. BMP-7 mRNA and protein was readily detected in tonsillar B cells,
      indicating a physiological relevance of the study. Altogether, we identified BMP
      7 as a negative regulator of GC B-cell survival. The effect was counteracted by
      truncated ALK5, suggesting greater complexity in regulating BMP-7 signaling than
      previously believed.

PMID- 28489885
TI  - Visit-to-visit glycemic variability is a strong predictor of chronic obstructive
      pulmonary disease in patients with type 2 diabetes mellitus: Competing risk
      analysis using a national cohort from the Taiwan diabetes study.
AB  - BACKGROUND: This study aims to examine the association between visit-to-visit
      glucose variability, which was measured by coefficient of variation (CV) of
      fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), and risk of chronic
      obstructive pulmonary disease (COPD) in a large number of patients with type 2
      diabetes with an average follow-up of 7.58 years. METHODS: We conducted a
      retrospective cohort study on 27,257 patients with type 2 diabetes who
      participated in the National Diabetes Case Management Program in Taiwan. Visit-to
      visit variability in HbA1c and FPG at baseline and the incidence of COPD were
      analyzed using a modified Cox proportional hazards model considering competing
      risks. RESULTS: A total of 2,346 incident cases of COPD. Patients were grouped
      into tertiles of FPG-CV and HbA1c-CV. The incidence rates in the first, second,
      and third tertiles were 9.87, 11.06, and 13.19, respectively, for FPG-CV and
      10.2, 11.81, and 12.07, for HbA1c-CV per 1000 person-years. After adjusting for
      age, gender, diabetes duration, treatment type, smoking, hypertension,
      hyperlipidemia, baseline FPG and HbA1c levels, and complications, both FPG-CV and
      HbA1c-CV were independently associated with COPD. The hazard ratios of COPD for
      the third terile compared with the first tertile of FPG-CV were 1.26 (95%
      confidence interval [CI]: 1.13-1.40). Moreover, the hazard ratios of COPD for the
      third and second tertiles compared with the first tertile of HbA1c-CV were 1.13
      (1.02-1.25) and 1.13 (1.02-1.26), respectively. CONCLUSIONS: Patients with FPG-CV
      higher than 34.6% or HbA1c-CV higher than 8.4% exhibited an increased risk of
      COPD. This finding confirmed the linear relationship of FPG-CV and HbA1c-CV to
      COPD. Visit-to-visit variability in FPG and HbA1c levels are strong predictors of
      COPD in patients with type 2 diabetes. Future studies should focus on lung
      dysfunction in diabetes, and adequate glucose control strategy in regular
      clinical practices must be established for COPD prevention.

PMID- 28489886
TI  - Bystander activation of irrelevant CD4+ T cells following antigen-specific
      vaccination occurs in the presence and absence of adjuvant.
AB  - Autoimmune and other chronic inflammatory diseases (AID) are prevalent diseases
      which can severely impact the quality of life of those that suffer from the
      disease. In most cases, the etiology of these conditions have remained unclear.
      Immune responses that take place e.g. during natural infection or after
      vaccination are often linked with the development or exacerbation of AID. It is
      highly debated if vaccines induce or aggravate AID and in particular adjuvants
      are mentioned as potential cause. Since vaccines are given on a large scale to
      healthy individuals but also to elderly and immunocompromised individuals, more
      research is warranted. Non-specific induction of naive or memory autoreactive T
      cells via bystander activation is one of the proposed mechanisms of how
      vaccination might be involved in AID. During bystander activation, T cells
      unrelated to the antigen presented can be activated without (strong) T cell
      receptor (TCR) ligation, but via signals derived from the ongoing response
      directed against the vaccine-antigen or adjuvant at hand. In this study we have
      set up a TCR transgenic T cell transfer mouse model by which we were able to
      measure local bystander activation of transferred and labeled CD4+ T cells.
      Intramuscular injection with the highly immunogenic Complete Freund's Adjuvant
      (CFA) led to local in vivo proliferation and activation of intravenously
      transferred CD4+ T cells in the iliac lymph node. This local bystander activation
      was also observed after CFA prime and Incomplete Freund's Adjuvant (IFA) boost
      injection. Furthermore, we showed that an antigen specific response is sufficient
      for the induction of a bystander activation response and the general, immune
      stimulating effect of CFA or IFA does not appear to increase this effect. In
      other words, no evidence was obtained that adjuvation of antigen specific
      responses is essential for bystander activation.

PMID- 28489887
TI  - Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4
      activated Wnt pathway.
AB  - AIM: Regorafenib is an oral small-molecule multi kinase inhibitor. Recently,
      several clinical trials have revealed that regorafenib has an anti-tumor activity
      in gastric cancer. However, only part of patients benefit from regorafenib, and
      the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In
      this study, we would assess the potential anti-tumor effects and the underlying
      mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers
      for patients selecting of regorafenib. METHODS: The anti-tumor effects of
      regorafenib on gastric cancer cells were analyzed via cell proliferation and
      invasion. The underlying mechanisms were demonstrated using molecular biology
      techniques. RESULTS: We found that regorafenib inhibited cell proliferation and
      invasion at the concentration of 20MUmol/L and in a dose dependent manner. The
      anti-tumor effects of regorafenib related to the decreased expression of CXCR4,
      and elevated expression and activation of CXCR4 could reverse the inhibition
      effect of regorafenib on gastric cancer cells. Further studies revealed that
      regorafenib reduced the transcriptional activity of Wnt/beta-Catenin pathway and
      led to decreased expression of Wnt pathway target genes, while overexpression and
      activation of CXCR4 could attenuate the inhibition effect of regorafenib on
      Wnt/beta-Catenin pathway. CONCLUSIONS: Our findings demonstrated that regorafenib
      effectively inhibited cell proliferation and invasion of gastric cancer cells via
      decreasing the expression of CXCR4 and further reducing the transcriptional
      activity of Wnt/beta-Catenin pathway.

PMID- 28489888
TI  - A two-question tool to assess the risk of repeated falls in the elderly.
AB  - INTRODUCTION: Older adults' perception of their own risk of fall has never been
      included into screening tools. The goal of this study was to evaluate the
      predictive validity of questions on subjects' self-perception of their own risk
      of fall. METHODS: This prospective study was conducted on a probabilistic sample
      of 772 Spanish community-dwelling older adults, who were followed-up for a one
      year period. At a baseline visit, subjects were asked about their recent history
      of falls (question 1: "Have you fallen in the last 6 months?"), as well as on
      their perception of their own risk of fall by using two questions (question 2:
      "Do you think you may fall in the next few months?" possible answers: yes/no;
      question 3: "What is the probability that you fall in the next few months?"
      possible answers: low/intermediate/high). The follow-up consisted of quarterly
      telephone calls, where the number of falls occurred in that period was recorded.
      RESULTS: A short questionnaire built with questions 1 and 3 showed 70%
      sensitivity (95% CI: 56%-84%), 72% specificity (95% CI: 68%-76%) and 0.74 area
      under the ROC curve (95% CI: 0.66-0.82) for prediction of repeated falls in the
      subsequent year. CONCLUSIONS: The estimation of one's own risk of fall has
      predictive validity for the occurrence of repeated falls in older adults. A short
      questionnaire including a question on perception of one's own risk of fall and a
      question on the recent history of falls had good predictive validity.

PMID- 28489889
TI  - An environmental assessment and risk map of Ascaris lumbricoides and Necator
      americanus distributions in Manufahi District, Timor-Leste.
AB  - BACKGROUND: In Timor-Leste there have been intermittent and ineffective soil
      transmitted helminth (STH) deworming programs since 2004. In a resource
      constrained setting, having information on the geographic distribution of STH can
      aid in prioritising high risk communities for intervention. This study aimed to
      quantify the environmental risk factors for STH infection and to produce a risk
      map of STH in Manufahi district, Timor-Leste. METHODOLOGY/PRINCIPAL FINDINGS:
      Georeferenced cross-sectional data and stool samples were obtained from 2,194
      participants in 606 households in 24 villages in the Manufahi District as part of
      cross sectional surveys done in the context of the "WASH for Worms" randomised
      controlled trial. Infection status was determined for Ascaris lumbricoides and
      Necator americanus using real-time quantitative polymerase chain reaction.
      Baseline infection data were linked to environmental data obtained for each
      household. Univariable and multivariable multilevel mixed-effects logistic
      regression analysis with random effects at the village and household level were
      conducted, with all models adjusted for age and sex. For A. lumbricoides, being a
      school-aged child increased the odds of infection, whilst higher temperatures in
      the coolest quarter of the year, alkaline soils, clay loam/loam soils and woody
      savannas around households were associated with decreased infection odds. For N.
      americanus, greater precipitation in the driest month, higher average enhanced
      vegetation index, age and sandy loam soils increased infection odds, whereas
      being female and living at higher elevations decreased the odds of infection.
      Predictive risk maps generated for Manufahi based upon these final models
      highlight the high predicted risk of N. americanus infection across the district
      and the more focal nature of A. lumbricoides infection. The predicted risk of any
      STH infection is high across the entire district. CONCLUSIONS/SIGNIFICANCE: The
      widespread predicted risk of any STH infection in 6 to 18 year olds provides
      strong evidence to support strategies for control across the entire geographical
      area. As few studies include soil texture and pH in their analysis, this study
      adds to a growing body of evidence suggesting these factors influence STH
      infection distribution. This study also further supports that A. lumbricoides
      prefers acidic soils, highlighting a potential relatively unexplored avenue for
      control. TRIAL REGISTRATION: ClinicalTrials.gov ACTRN12614000680662.

PMID- 28489890
TI  - Unmasking inequalities: Sub-national maternal and child mortality data from two
      urban slums in Lagos, Nigeria tells the story.
AB  - INTRODUCTION: Nigeria has one of the highest maternal mortality ratios in the
      world as well as high perinatal mortality. Unfortunately, the country does not
      have the resources to assess this critical indicator with the conventional health
      information system and measuring its progress toward the goal of ending
      preventable maternal deaths is almost impossible. Medecins Sans Frontieres (MSF)
      conducted a cross-sectional study to assess maternal and perinatal mortality in
      Makoko Riverine and Badia East, two of the most vulnerable slums of Lagos.
      MATERIALS AND METHODS: The study was a cross-sectional, community-based household
      survey. Nearly 4,000 households were surveyed. The sisterhood method was utilized
      to estimate maternal mortality and the preceding births technique was used to
      estimate newborn and child mortality. Questions regarding health seeking behavior
      were posed to female interviewees and self-reported data were collected. RESULTS:
      Data was collected from 3963 respondents for a total of 7018 sisters ever
      married. The maternal mortality ratio was calculated at 1,050/100,000 live births
      (95% CI: 894-1215), and the lifetime risk of maternal death at 1:18. The neonatal
      mortality rate was extracted from 1967 pregnancies reported and was estimated at
      28.4/1,000; infant mortality at 43.8/1,000 and under-five mortality at 103/1,000.
      Living in Badia, giving birth at home and belonging to the Egun ethnic group were
      associated with higher perinatal mortality. Half of the last pregnancies were
      reportedly delivered in private health facilities. Proximity to home was the main
      influencing factor (32.4%) associated with delivery at the health facility.
      DISCUSSION: The maternal mortality ratio found in these urban slum populations
      within Lagos is extremely high, compared to the figure estimated for Lagos State
      of 545 per 100,000 live births. Urgent attention is required to address these
      neglected and vulnerable neighborhoods. Efforts should be invested in obtaining
      data from poor, marginalized, and hard-to-reach populations in order to identify
      pockets of marginalization needing additional resources and tailored approaches
      to guarantee equitable treatment and timely access to quality health services for
      vulnerable groups. This study demonstrates the importance of sub-regional,
      disaggregated data to identify and redress inequities that exist among poor,
      remote, vulnerable populations-as in the urban slums of Lagos.

PMID- 28489891
TI  - RNA-seq approach to analysis of gene expression profiles in dark green islands
      and light green tissues of Cucumber mosaic virus-infected Nicotiana tabacum.
AB  - Dark green islands (DGIs) surrounded by light green tissues (LGTs) are common
      leaf symptoms of plants that are systemically infected by various viruses that
      induce leaf mosaic in infected plants. The inoculation of Cucumber mosaic virus
      (CMV) in Nicotiana tabacum produced a commonly occurring sequence of classic
      patterns of DGIs and LGTs. Previous studies confirmed that there are significant
      differences between DGIs and LGTs in terms of physiology, biochemistry and
      molecular biology, but the mechanisms by which DGIs form remain unclear. To
      investigate the global gene expression changes that occur in these special
      tissues, individual differential gene expression tag libraries were constructed
      from three total RNA samples isolated from DGIs, LGTs and control plants (CK) and
      were sequenced using an Illumina HiSeqTM 2000. An analysis of differentially
      expressed genes (DEGs) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway enrichment analysis were performed. These analyses
      revealed the differences between DGIs, LGTs and CK. GO enrichment and KEGG
      pathway analyses suggested that several pathways related to photosynthesis and
      chlorophyll metabolism were enriched in DGIs compared to LGTs and CK. Several
      pathways related to apoptosis were significantly up-regulated in LGTs compared to
      DGIs. Additionally, we identified sets of DEGs that may be related to the
      formation or development of DGIs and LGTs. Our systematic analyses provide
      comprehensive transcriptomic information regarding DGIs and LGTs in CMV-infected
      N. tabacum. These data will help characterize the detailed mechanisms of DGI and
      LGT formation.

PMID- 28489893
TI  - Correction: Novel decay dynamics revealed for virus-mediated drug activation in
      cytomegalovirus infection.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1006299.].

PMID- 28489892
TI  - Exposure to maternal obesogenic diet worsens some but not all pre-cancer
      phenotypes in a murine genetic model of prostate cancer.
AB  - Prostate cancer research has been predominantly focused on adult exposures and
      risk factors. However, because the prostate develops during gestation and early
      life, exposure to external factors, such as obesity, during development could
      affect the prostate cancer progression in adults. Our previous work demonstrated
      that exposure to a high fat/high sugar (HF/HS) diet during gestation and until
      weaning stimulated prostate hyperplasia and altered the Pten/Akt pathway in adult
      mice fed a normal diet after weaning. Here, we asked whether maternal exposure to
      HF/HS would worsen prostate phenotypes in mice lacking Pten, a widely accepted
      driver of prostate cancer. We found that, at six weeks of age, both Chow
      (control)-and HF/HS-exposed Pten knockout mice showed evidence of murine PIN that
      included ducts with central comedo necrosis but that the HF/HS exposure did not
      influence murine PIN progression. The Pten knockout mice exposed to HF/HS in
      utero had significantly more mitotic cells than Pten knockouts exposed to Chow
      diet. In the Pten null background, the maternal HF/HS diet enhanced proliferation
      but did not have an additive effect on Akt activation. We observed neuroendocrine
      differentiation in Pten knockout mice, a phenotype that had not been previously
      described in this model.

PMID- 28489895
TI  - Flowering after disaster: Early Danian buckthorn (Rhamnaceae) flowers and leaves
      from Patagonia.
AB  - Southern-Hemisphere terrestrial communities from the early Paleocene are poorly
      known, but recent work on Danian plant fossils from the Salamanca Formation in
      Chubut Province, Argentina are providing critical data on earliest Paleocene
      floras. The fossils described here come from a site in the Salamanca Formation
      dating to ca. 1 million years or less after the end-Cretaceous extinction event;
      they are the first fossil flowers reported from the Danian of South America, and
      possible the entire Southern Hemisphere. They are compressions and impressions in
      flat-laminated light gray shale, and they belong to the family Rhamnaceae
      (buckthorns). Flowers of Notiantha grandensis gen. et sp. nov. are pentamerous,
      with distinctly keeled calyx lobes projecting from the hypanthium, clawed and
      cucullate emarginate petals, antepetalous stamens, and a pentagonal floral disk
      that fills the hypanthium. Their phylogenetic position was evaluated using a
      molecular scaffold approach combined with morphological data. Results indicate
      that the flowers are most like those of extant ziziphoid Rhamnaceae. The
      associated leaves, assigned to Suessenia grandensis gen. et sp. nov. are simple
      and ovate, with serrate margins and three acrodromous basal veins. They conform
      to the distinctive leaves of some extant Rhamnaceae in the ziziphoid and
      ampelozizyphoid clades. These fossils provide the first unequivocal megafossil
      evidence of Rhamnaceae in the Southern Hemisphere, demonstrating that Rhamnaceae
      expanded beyond the tropics by the earliest Paleocene. Given previous reports of
      rhamnaceous pollen in the late Paleogene and Neogene of Antarctica and southern
      Australia, this new occurrence increases the possibility of high-latitude
      dispersal of this family between South America and Australia via Antarctica
      during the Cenozoic.

PMID- 28489894
TI  - Analysis of global DNA methylation changes in primary human fibroblasts in the
      early phase following X-ray irradiation.
AB  - Epigenetic alterations may contribute to the generation of cancer cells in a
      multi-step process of tumorigenesis following irradiation of normal body cells.
      Primary human fibroblasts with intact cell cycle checkpoints were used as a model
      to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic
      effects (within the first cell cycle) in the exposed cells. ELISA-based
      fluorometric assays were consistent with slightly reduced global DNA methylation
      and hydroxymethylation, however the observed between-group differences were
      usually not significant. Similarly, bisulfite pyrosequencing of interspersed LINE
      1 repeats and centromeric alpha-satellite DNA did not detect significant
      methylation differences between irradiated and non-irradiated cultures.
      Methylation of interspersed ALU repeats appeared to be slightly increased (one
      percentage point; p = 0.01) at 6 h after irradiation with 4 Gy. Single-cell
      analysis showed comparable variations in repeat methylation among individual
      cells in both irradiated and control cultures. Radiation-induced changes in
      global repeat methylation, if any, were much smaller than methylation variation
      between different fibroblast strains. Interestingly, alpha-satellite DNA
      methylation positively correlated with gestational age. Finally, 450K methylation
      arrays mainly targeting genes and CpG islands were used for global DNA
      methylation analysis. There were no detectable methylation differences in genic
      (promoter, 5' UTR, first exon, gene body, 3' UTR) and intergenic regions between
      irradiated and control fibroblast cultures. Although we cannot exclude minor
      effects, i.e. on individual CpG sites, collectively our data suggest that global
      DNA methylation remains rather stable in irradiated normal body cells in the
      early phase of DNA damage response.

PMID- 28489896
TI  - Short-term activity cycles impede information transmission in ant colonies.
AB  - Rhythmical activity patterns are ubiquitous in nature. We study an oscillatory
      biological system: collective activity cycles in ant colonies. Ant colonies have
      become model systems for research on biological networks because the interactions
      between the component parts are visible to the naked eye, and because the time
      ordered contact network formed by these interactions serves as the substrate for
      the distribution of information and other resources throughout the colony. To
      understand how the collective activity cycles influence the contact network
      transport properties, we used an automated tracking system to record the movement
      of all the individuals within nine different ant colonies. From these
      trajectories we extracted over two million ant-to-ant interactions. Time-series
      analysis of the temporal fluctuations of the overall colony interaction and
      movement rates revealed that both the period and amplitude of the activity cycles
      exhibit a diurnal cycle, in which daytime cycles are faster and of greater
      amplitude than night cycles. Using epidemiology-derived models of transmission
      over networks, we compared the transmission properties of the observed periodic
      contact networks with those of synthetic aperiodic networks. These simulations
      revealed that contrary to some predictions, regularly-oscillating contact
      networks should impede information transmission. Further, we provide a
      mechanistic explanation for this effect, and present evidence in support of it.

PMID- 28489897
TI  - Analysis of statistical and standard algorithms for detecting muscle onset with
      surface electromyography.
AB  - The timing of muscle activity is a commonly applied analytic method to understand
      how the nervous system controls movement. This study systematically evaluates six
      classes of standard and statistical algorithms to determine muscle onset in both
      experimental surface electromyography (EMG) and simulated EMG with a known onset
      time. Eighteen participants had EMG collected from the biceps brachii and vastus
      lateralis while performing a biceps curl or knee extension, respectively. Three
      established methods and three statistical methods for EMG onset were evaluated.
      Linear envelope, Teager-Kaiser energy operator + linear envelope and sample
      entropy were the established methods evaluated while general time series
      mean/variance, sequential and batch processing of parametric and nonparametric
      tools, and Bayesian changepoint analysis were the statistical techniques used.
      Visual EMG onset (experimental data) and objective EMG onset (simulated data)
      were compared with algorithmic EMG onset via root mean square error and linear
      regression models for stepwise elimination of inferior algorithms. The top
      algorithms for both data types were analyzed for their mean agreement with the
      gold standard onset and evaluation of 95% confidence intervals. The top
      algorithms were all Bayesian changepoint analysis iterations where the parameter
      of the prior (p0) was zero. The best performing Bayesian algorithms were p0 = 0
      and a posterior probability for onset determination at 60-90%. While existing
      algorithms performed reasonably, the Bayesian changepoint analysis methodology
      provides greater reliability and accuracy when determining the singular onset of
      EMG activity in a time series. Further research is needed to determine if this
      class of algorithms perform equally well when the time series has multiple bursts
      of muscle activity.

PMID- 28489899
TI  - Development of an immunochromatographic strip test for the rapid detection of
      zearalenone in wheat from Jiangsu province, China.
AB  - A colloidal gold (ICS) test was developed for rapid detection of zearalenone
      (ZEN) in wheat samples. The mAb against ZEN was prepared in our laboratory and
      labelled with colloidal gold as a probe for the ICS test. The conditions were
      optimized and 30 nm colloidal gold nanoparticles were chosen for optimal
      performance. Millipore 135 was chosen as the NC membrane for its level of
      sensitivity. The optimum amount of coated antigen ZEN-OVA and anti-ZEN mAb was
      0.5 mg/mL and 8 MUg/mL, respectively. The ICS test, which has a detection limit
      of 15 ng/mL for ZEN, could be completed in 5 min. Analysis of ZEN in 202 wheat
      samples over three consecutive years revealed that data obtained from the ICS
      test were in a good agreement with LC-MS/MS data. This result demonstrated that
      the ICS test could be used as a qualitative tool to screen on-site for ZEN.

PMID- 28489898
TI  - Comparative genomic study of ALDH gene superfamily in Gossypium: A focus on
      Gossypium hirsutum under salt stress.
AB  - Aldehyde dehydrogenases (ALDHs) are a superfamily of enzymes which play important
      role in the scavenging of active aldehydes molecules. In present work, a
      comprehensive whole-genomic study of ALDH gene superfamily was carried out for an
      allotetraploid cultivated cotton species, G. hirsutum, as well as in parallel
      relative to their diploid progenitors, G. arboreum and G. raimondii. Totally, 30
      and 58 ALDH gene sequences belong to 10 families were identified from diploid and
      allotetraploid cotton species, respectively. The gene structures among the
      members from same families were highly conserved. Whole-genome duplication and
      segmental duplication might be the major driver for the expansion of ALDH gene
      superfamily in G. hirsutum. In addition, the expression patterns of GhALDH genes
      were diverse across tissues. Most GhALDH genes were induced or repressed by salt
      stress in upland cotton. Our observation shed lights on the molecular
      evolutionary properties of ALDH genes in diploid cottons and their
      alloallotetraploid derivatives. It may be useful to mine key genes for
      improvement of cotton response to salt stress.

PMID- 28489900
TI  - Scanning double-sided documents without incurring show-through by learning to
      fuse two complementary images using multilayer perceptron.
AB  - This paper presents a novel method for scanning duplex-printed documents without
      incurring the unwanted show-through artifact. The proposed method achieves the
      goal of eliminating the leaked-out reverse-side content by fusing a white backed
      scan image with a black backed scan image of the document. The fusion is
      accomplished using a multilayer perceptron having learned a fusion mapping from
      manually corrected document images. The main novel contributions of this work
      include (1) being the first to propose to accomplish the goal of show through
      free scanning by fusing a white backed scan image with a black backed scan image
      of the document; (2) proposing a learning approach using a multilayer perceptron
      to learn the fusion mapping from manually corrected scan images; and (3)
      proposing to use the pixel value histogram of reverse-side-printed area as well
      as the pixel value histogram of duplex-printed area to quantitatively indicate
      show through severity to facilitate objective comparison of the methods in
      consideration. The experiment results show that the proposed method is remarkably
      more powerful in eliminating show through than the two state-of-the-art methods
      in comparison.

PMID- 28489901
TI  - Characterization and proteomic profile of extracellular vesicles from peritoneal
      dialysis efflux.
AB  - Peritoneal Dialysis (PD) is considered the best option for a cost-effective mid
      term dialysis in patients with Chronic Renal Failure. However, functional failure
      of the peritoneal membrane (PM) force many patients to stop PD treatment and
      start haemodialysis. Currently, PM functionality is monitored by the peritoneal
      equilibration test, a tedious technique that often show changes when the membrane
      damage is advanced. As in other pathologies, the identification and
      characterization of extracellular vesicles (EVs) in the peritoneal dialysis
      efflux (PDE) may represent a non-invasive alternative to identify biomarkers of
      membrane failure. Using size-exclusion chromatography, we isolated EVs from PDE
      in a group of patients. Vesicles were characterized by the presence of
      tetraspanin markers, nanoparticle tracking analysis profile, cryo-electron
      microscopy and mass spectrometry. Here, we report the isolation and
      characterization of PDE-EVs. Based on mass spectrometry, we have found a set of
      well-conserved proteins among patients. Interestingly, the peptide profile also
      revealed remarkable changes between newly enrolled and longer-treated PD
      patients. These results are the first step to the identification of PDE-EVs based
      new markers of PM damage, which could support clinicians in their decision-making
      in a non-invasive manner.

PMID- 28489902
TI  - Disturbance of a rare seabird by ship-based tourism in a marine protected area.
AB  - Managers of marine protected areas (MPAs) must often seek ways to allow for
      visitation while minimizing impacts to the resources they are intended to
      protect. Using shipboard observers, we quantified the "zone of disturbance" for
      Kittlitz's and marbled murrelets (Brachyramphus brevirostris and B. marmoratus)
      exposed to large cruise ships traveling through Glacier Bay National Park, one of
      the largest MPAs in North America. In the upper reaches of Glacier Bay, where
      Kittlitz's murrelets predominated, binary logistic regression models predicted
      that 61% of all murrelets within 850 m perpendicular distance of a cruise ship
      were disturbed (defined as flushing or diving), whereas in the lower reaches,
      where marbled murrelets predominated, this percentage increased to 72%. Using
      survival analysis, murrelets in both reaches were found to react at greater
      distances when ships approached indirectly, presumably because of the ship's
      larger profile, suggesting murrelets responded to visual rather than audio cues.
      No management-relevant covariates (e.g., ship velocity, route distance from
      shore) were found to be important predictors of disturbance, as distance from
      ship to murrelet accounted for > 90% of the explained variation in murrelet
      response. Utilizing previously published murrelet density estimates from Glacier
      Bay, and applying an average empirical disturbance probability (68%) out to 850 m
      from a cruise ship's typical route, we estimated that a minimum of 9.8-19.6% of
      all murrelets in Glacier Bay are disturbed per ship entry. Whether these
      disturbance levels are inconsistent with Park management objectives, which
      include conserving wildlife as well as providing opportunities for visitation,
      depends in large part on whether disturbance events caused by cruise ships have
      impacts on murrelet fitness, which remains uncertain.

PMID- 28489903
TI  - Atoll-scale patterns in coral reef community structure: Human signatures on
      Ulithi Atoll, Micronesia.
AB  - The dynamic relationship between reefs and the people who utilize them at a
      subsistence level is poorly understood. This paper characterizes atoll-scale
      patterns in shallow coral reef habitat and fish community structure, and
      correlates these with environmental characteristics and anthropogenic factors,
      critical to conservation efforts for the reefs and the people who depend on them.
      Hierarchical clustering analyses by site for benthic composition and fish
      community resulted in the same 3 major clusters: cluster 1-oceanic (close
      proximity to deep water) and uninhabited (low human impact); cluster 2-oceanic
      and inhabited (high human impact); and cluster 3-lagoonal (facing the inside of
      the lagoon) and inhabited (highest human impact). Distance from village, reef
      exposure to deep water and human population size had the greatest effect in
      predicting the fish and benthic community structure. Our study demonstrates a
      strong association between benthic and fish community structure and human use
      across the Ulithi Atoll (Yap State, Federated States of Micronesia) and confirms
      a pattern observed by local people that an 'opportunistic' scleractinian coral
      (Montipora sp.) is associated with more highly impacted reefs. Our findings
      suggest that small human populations (subsistence fishing) can nevertheless have
      considerable ecological impacts on reefs due, in part, to changes in fishing
      practices rather than overfishing per se, as well as larger global trends.
      Findings from this work can assist in building local capacity to manage reef
      resources across an atoll-wide scale, and illustrates the importance of
      anthropogenic impact even in small communities.

PMID- 28489904
TI  - Underreporting of high-risk water and sanitation practices undermines progress on
      global targets.
AB  - Water and sanitation indicators under the Millennium Development Goals failed to
      capture high-risk practices undertaken on a regular basis. In conjunction with
      local partners, fourteen rounds of household surveys using mobile phones with a
      customized open-source application were conducted across nine study geographies
      in Asia and Africa. In addition to the main water and sanitation facilities,
      interviewees (n = 245,054) identified all water and sanitation options regularly
      used for at least one season of the year. Unimproved water consumption and open
      defecation were targeted as high-risk practices. We defined underreporting as the
      difference between the regular and main use of high-risk practices. Our estimates
      of high-risk practices as the main option matched the widely accepted Demographic
      and Health Surveys (DHS) estimates within the 95% confidence interval. However,
      estimates of these practices as a regular option was far higher than the DHS
      estimates. Across the nine geographies, median underreporting of unimproved water
      use was 5.5%, with a range of 0.5% to 13.9%. Median underreporting of open
      defecation was much higher at 9.9%, with a range of 2.7% to 11.5%. This resulted
      in an underreported population of 25 million regularly consuming unimproved water
      and 50 million regularly practicing open defecation. Further examination of data
      from Ethiopia suggested that location and socio-economic factors were significant
      drivers of underreporting. Current global monitoring relies on a framework that
      considers the availability and use of a single option to meet drinking water and
      sanitation needs. Our analysis demonstrates the use of multiple options and
      widespread underreporting of high-risk practices. Policies based on current
      monitoring data, therefore, fail to consider the range of challenges and
      solutions to meeting water and sanitation needs, and result in an inflated sense
      of progress. Mobile surveys offer a cost-effective and innovative platform to
      rapidly and repeatedly monitor critical development metrics.

PMID- 28489905
TI  - An investigation of modelling and design for software service applications.
AB  - Software services offer the opportunity to use a component-based approach for the
      design of applications. However, this needs a deeper understanding of how to
      develop service-based applications in a systematic manner, and of the set of
      properties that need to be included in the 'design model'. We have used a
      realistic application to explore systematically how service-based designs can be
      created and described. We first identified the key properties of an SOA (service
      oriented architecture) and then undertook a single-case case study to explore its
      use in the development of a design for a large-scale application in energy
      engineering, modelling this with existing notations wherever possible. We
      evaluated the resulting design model using two walkthroughs with both domain and
      application experts. We were able to successfully develop a design model around
      the ten properties identified, and to describe it by adapting existing design
      notations. A component-based approach to designing such systems does appear to be
      feasible. However, it needs the assistance of a more integrated set of notations
      for describing the resulting design model.

PMID- 28489906
TI  - Neocortical activity is stimulus- and scale-invariant.
AB  - Mounting evidence supports the hypothesis that the cortex operates near a
      critical state, defined as the transition point between order (large-scale
      activity) and disorder (small-scale activity). This criticality is manifested by
      power law distribution of the size and duration of spontaneous cascades of
      activity, which are referred as neuronal avalanches. The existence of such
      neuronal avalanches has been confirmed by several studies both in vitro and in
      vivo, among different species and across multiple spatial scales. However,
      despite the prevalence of scale free activity, still very little is known
      concerning whether and how the scale-free nature of cortical activity is altered
      during external stimulation. To address this question, we performed in vivo two
      photon population calcium imaging of layer 2/3 neurons in primary visual cortex
      of behaving mice during visual stimulation and conducted statistical analyses on
      the inferred spike trains. Our investigation for each mouse and condition
      revealed power law distributed neuronal avalanches, and irregular spiking
      individual neurons. Importantly, both the avalanche and the spike train
      properties remained largely unchanged for different stimuli, while the cross
      correlation structure varied with stimuli. Our results establish that
      microcircuits in the visual cortex operate near the critical regime, while
      rearranging functional connectivity in response to varying sensory inputs.

PMID- 28489908
TI  - Sexual dimorphism in African elephant social rumbles.
AB  - This study used the source and filter theory approach to analyse sex differences
      in the acoustic features of African elephant (Loxodonta africana) low-frequency
      rumbles produced in social contexts ('social rumbles'). Permuted discriminant
      function analysis revealed that rumbles contain sufficient acoustic information
      to predict the sex of a vocalizing individual. Features primarily related to the
      vocalizer's size, i.e. fundamental frequency variables and vocal tract resonant
      frequencies, differed significantly between the sexes. Yet, controlling for age
      and size effects, our results indicate that the pronounced sexual size dimorphism
      in African elephants is partly, but not exclusively, responsible for sexual
      differences in social rumbles. This provides a scientific foundation for future
      work investigating the perceptual and functional relevance of specific acoustic
      characteristics in African elephant vocal sexual communication.

PMID- 28489909
TI  - Correction: Buzz Factor or Innovation Potential: What Explains Cryptocurrencies'
      Returns?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0169556.].

PMID- 28489907
TI  - Anti-oxidative effects of 4-hydroxybenzyl alcohol in astrocytes confer protective
      effects in autocrine and paracrine manners.
AB  - 4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia
      elata Blume (GEB), a traditional herbal medicine used in East Asia. Many
      activities have been reported to underlie the beneficial effects of 4-HBA in the
      brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc
      toxic effects have been implicated in the postischemic brain. Here, the authors
      investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to
      identify the underlying molecular mechanisms involved. 4-HBA dose-dependently
      suppressed H2O2-induced astrocyte cell death. More specifically, pre-incubation
      of C6 cells (an astrocyte cell line) with 100 MUM 4-HBA for 6 hrs increased
      survival when cells were treated with H2O2 (100 MUM, 1 hr) from 54.2+/-0.7% to
      85.9+/-1.5%. In addition, 4-HBA was found to up-regulate and activate Nrf2, and
      subsequently, to induce the expressions of several anti-oxidative genes, such as,
      HO-1, NQO1, and GCLM. Notably, HO-1 was induced by 3.4-fold in 4-HBA-treated C6
      cells, and siRNA-mediated HO-1 knockdown demonstrated that Nrf2 activation and HO
      1 induction were responsible for the observed cytoprotective effect of 4-HBA. ERK
      and Akt signaling pathways were activated by 4-HBA in C6 cells, suggesting their
      involvements in protective effect of 4-HBA. In addition, 4-HBA-conditioned
      astrocyte culture medium was found to have neuroprotective effects on primary
      neuronal cultures or fresh C6 cells exposed to oxidative stress, and these
      effects seemed to be mediated by glial cell line-derived neurotrophic factor
      (GDNF) and vascular endothelial growth factor (VEGF), which both accumulated in 4
      HBA-treated astrocyte culture media. Thus, the 4-HBA-mediated activation of Nrf2
      and induction of HO-1 in astrocytes were found to act via autocrine and paracrine
      mechanisms to confer protective effects. Furthermore, given the pleiotropic
      effects of 4-HBA with respect to its targeting of various brain cell types and
      functions, it would appear that 4-HBA has therapeutic potential for the
      prevention and amelioration of various brain diseases.

PMID- 28489910
TI  - Random domain name and address mutation (RDAM) for thwarting reconnaissance
      attacks.
AB  - Network address shuffling is a novel moving target defense (MTD) that invalidates
      the address information collected by the attacker by dynamically changing or
      remapping the host's network addresses. However, most network address shuffling
      methods are limited by the limited address space and rely on the host's static
      domain name to map to its dynamic address; therefore these methods cannot
      effectively defend against random scanning attacks, and cannot defend against an
      attacker who knows the target's domain name. In this paper, we propose a network
      defense method based on random domain name and address mutation (RDAM), which
      increases the scanning space of the attacker through a dynamic domain name method
      and reduces the probability that a host will be hit by an attacker scanning IP
      addresses using the domain name system (DNS) query list and the time window
      methods. Theoretical analysis and experimental results show that RDAM can defend
      against scanning attacks and worm propagation more effectively than general
      network address shuffling methods, while introducing an acceptable operational
      overhead.

PMID- 28489911
TI  - Human beta-defensin-2 production upon viral and bacterial co-infection is
      attenuated in COPD.
AB  - Viral-bacterial co-infections are associated with severe exacerbations of COPD.
      Epithelial antimicrobial peptides, including human beta-defensin-2 (HBD-2), are
      integral to innate host defenses. In this study, we examined how co-infection of
      airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD
      2 expression, and whether these responses are attenuated by cigarette smoke and
      in epithelial cells obtained by bronchial brushings from smokers with normal lung
      function or from COPD patients. When human airway epithelial cells from normal
      lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination,
      co-infection with rhinovirus and bacteria resulted in synergistic induction of
      HBD-2 (p<0.05). The combination of virus and flagellin replicated this
      synergistic increase (p<0.05), and synergy was not seen using a flagella
      deficient mutant Pseudomonas (p<0.05). The effects of Pseudomonas aeruginosa were
      mediated via interactions of flagellin with TLR5. The effects of HRV-16 depended
      upon viral replication but did not appear to be mediated via the intracellular
      RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation
      associated gene-5. Cigarette smoke extract significantly decreased HBD-2
      production in response to co-infection. Attenuated production was also observed
      following co-infection of cells obtained from healthy smokers or COPD patients
      compared to healthy controls (p<0.05). We conclude that co-exposure to HRV-16 and
      Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial
      cells and that this synergistic induction of HBD-2 is reduced in COPD patients.
      This may contribute to the more severe exacerbations these patients experience in
      response to viral-bacterial co-infections.

PMID- 28489912
TI  - Eight habitats, 38 threats and 55 experts: Assessing ecological risk in a multi
      use marine region.
AB  - Identifying the relative risk human activities pose to a habitat, and the
      ecosystem services they provide, can guide management prioritisation and resource
      allocation. Using a combination of expert elicitation to assess the probable
      effect of a threat and existing data to assess the level of threat exposure, we
      conducted a risk assessment for 38 human-mediated threats to eight marine
      habitats (totalling 304 threat-habitat combinations) in Spencer Gulf, Australia.
      We developed a score-based survey to collate expert opinion and assess the
      relative effect of each threat to each habitat, as well as a novel and
      independent measure of knowledge-based uncertainty. Fifty-five experts
      representing multiple sectors and institutions participated in the study, with 6
      to 15 survey responses per habitat (n = 81 surveys). We identified key threats
      specific to each habitat; overall, climate change threats received the highest
      risk rankings, with nutrient discharge identified as a key local-scale stressor.
      Invasive species and most fishing-related threats, which are commonly identified
      as major threats to the marine environment, were ranked as low-tier threats to
      Spencer Gulf, emphasising the importance of regionally-relevant assessments.
      Further, we identified critical knowledge gaps and quantified uncertainty scores
      for each risk. Our approach will facilitate prioritisation of resource allocation
      in a region of increasing social, economic and environmental importance, and can
      be applied to marine regions where empirical data are lacking.

PMID- 28489913
TI  - Human perception of electrical stimulation on the surface of somatosensory
      cortex.
AB  - Recent advancement in electrocorticography (ECoG)-based brain-computer interface
      technology has sparked a new interest in providing somatosensory feedback using
      ECoG electrodes, i.e., cortical surface electrodes. We conducted a 28-day study
      of cortical surface stimulation in an individual with arm paralysis due to
      brachial plexus injury to examine the sensation produced by electrical
      stimulation of the somatosensory cortex. A high-density ECoG grid was implanted
      over the somatosensory and motor cortices. Stimulation through cortical surface
      electrodes over the somatosensory cortex successfully elicited arm and hand
      sensations in our participant with chronic paralysis. There were three key
      findings. First, the intensity of perceived sensation increased monotonically
      with both pulse amplitude and pulse frequency. Second, changing pulse width
      changed the type of sensation based on qualitative description provided by the
      human participant. Third, the participant could distinguish between stimulation
      applied to two neighboring cortical surface electrodes, 4.5 mm center-to-center
      distance, for three out of seven electrode pairs tested. Taken together, we found
      that it was possible to modulate sensation intensity, sensation type, and evoke
      sensations across a range of locations from the fingers to the upper arm using
      different stimulation electrodes even in an individual with chronic impairment of
      somatosensory function. These three features are essential to provide effective
      somatosensory feedback for neuroprosthetic applications.

PMID- 28489915
TI  - An 8.5 m long ammonite drag mark from the Upper Jurassic Solnhofen Lithographic
      Limestones, Germany.
AB  - Trackways and tracemakers preserved together in the fossil record are rare.
      However, the co-occurrence of a drag mark, together with the dead animal that
      produced it, is exceptional. Here, we describe an 8.5 m long ammonite drag mark
      complete with the preserved ammonite shell (Subplanites rueppellianus) at its
      end. Previously recorded examples preserve ammonites with drag marks of < 1 m.
      The specimen was recovered from a quarry near Solnhofen, southern Germany. The
      drag mark consists of continuous parallel ridges and furrows produced by the ribs
      of the ammonite shell as it drifted just above the sediment surface, and does not
      reflect behaviour of the living animal.

PMID- 28489914
TI  - miR-27a and miR-449b polymorphisms associated with a risk of idiopathic recurrent
      pregnancy loss.
AB  - OBJECTIVE: MicroRNAs (miRNAs) regulate gene expression during the peri
      implantation period. The purpose of this study was to investigate whether genetic
      polymorphisms in the four miRNAs associated with fetal or placental development
      play roles in the development of idiopathic recurrent pregnancy loss (RPL) in
      Korean females. STUDY DESIGN: A case-control study involving 225 controls and 387
      women with at least two consecutively recurrent pregnancy losses between 1999 and
      2012 was performed. The genotypes of the four miRNA polymorphisms, including miR
      27a rs895819, miR-423 rs6505162, miR-449b rs10061133, and miR-605 rs2043556, were
      analyzed by the polymerase chain reaction-restriction fragment length
      polymorphism assay. Odds ratios and 95% confidence intervals were estimated using
      multivariate analyses after maternal age adjustments. The relationships between
      each of the four microRNA genotypes and each of the six clinical parameters of
      the RPL patients (plasma homocysteine and folate levels, natural killer cell
      number, platelet count, prothrombin time, and, activated partial thromboplastin
      time) were analyzed using multiple linear regression analyses. RESULTS: Our
      results suggest that weak associations between decreased RPL risk and the
      genotypes of miR-27a (AG and AG+GG), combination genotype of miR-27a/miR-423
      (AG/GC), and haplotypes of miR-27a/miR-423/miR-449b/miR-605 (G-C-A-G) and miR
      27a/miR-449b/miR-605 (G-A-G), whereas weak associations between increased RPL
      risk and genotypes of miR-449b (GG and AG+GG), combination genotypes of miR
      423/miR-449b (CC/GG and CA/AG), miR-449b/miR-605 (AG/AG), haplotypes of miR
      27a/miR-423/miR-449b/miR-605 (A-C-G-A, A-A-A-G, and G-C-G-G), miR-27a/miR-423/miR
      449b (A-C-G), miR-27a/miR-449b/miR-605 (A-A-G, A-G-A, and G-G-G), miR-423/miR
      449b/miR-605 (C-G-G and A-A-G), and miR-423/miR-449b (C-G and A-A). The genotypes
      of miR-27a (AG and AG+GG) also showed significant contributions to the prediction
      of folate levels in RPL patients. CONCLUSIONS: The study showed associations
      between miRNA polymorphisms (miR-27a rs895819 and miR-449b rs10061133) and RPL
      development, and between the miRNA polymorphism (miR-27a rs895819) and plasma
      folate levels.

PMID- 28489917
TI  - Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of
      the opportunistic pathogen Pseudomonas aeruginosa.
AB  - It is generally thought that mucosal fluids protect underlying epithelial
      surfaces against opportunistic infection via their antimicrobial activity.
      However, our published data show that human tear fluid can protect against the
      major opportunistic pathogen Pseudomonas aeruginosa independently of
      bacteriostatic activity. Here, we explored the mechanisms for tear protection,
      focusing on impacts of tear fluid on bacterial virulence factor expression.
      Results showed that tear fluid suppressed twitching motility, a type of surface
      associated movement conferred by pili. Previously, we showed that twitching is
      critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial
      cells after internalization, and corneal virulence. Inhibition of twitching by
      tear fluid was dose-dependent with dilutions to 6.25% retaining activity.
      Purified lactoferrin, lysozyme, and contrived tears containing these, and many
      other, tear components lacked the activity. Systematic protein fractionation,
      mass spectrometry, and immunoprecipitation identified the glycoprotein DMBT1
      (Deleted in Malignant Brain Tumors 1) in tear fluid as required. DMBT1 purified
      from human saliva also inhibited twitching, as well as P. aeruginosa traversal of
      human corneal epithelial cells in vitro, and reduced disease pathology in a
      murine model of corneal infection. DMBT1 did not affect PilA expression, nor
      bacterial intracellular cyclicAMP levels, and suppressed twitching motility of P.
      aeruginosa chemotaxis mutants (chpB, pilK), and an adenylate cyclase mutant
      (cyaB). However, dot-immunoblot assays showed purified DMBT1 binding of pili
      extracted from PAO1 suggesting that twitching inhibition may involve a direct
      interaction with pili. The latter could affect extension or retraction of pili,
      their interactions with biotic or abiotic surfaces, or cause their aggregation.
      Together, the data suggest that DMBT1 inhibition of twitching motility
      contributes to the mechanisms by which mucosal fluids protect against P.
      aeruginosa infection. This study also advances our understanding of how mucosal
      fluids protect against infection, and suggests directions for novel biocompatible
      strategies to protect our surface epithelia against a major opportunistic
      pathogen.

PMID- 28489918
TI  - OCT-angiography: A qualitative and quantitative comparison of 4 OCT-A devices.
AB  - PURPOSE: To compare the quality of four OCT-angiography(OCT-A) modules. METHOD:
      The retina of nineteen healthy volunteers were scanned with four OCT-devices
      (Topcon DRI-OCT Triton Swept-source OCT, Optovue RTVue-XR, a prototype Spectralis
      OCT2, Heidelberg-Engineering and Zeiss Cirrus 5000-HD-OCT). The device-software
      generated en-face OCT-A images of the superficial (SCP) and deep capillary
      plexuses (DCP) were evaluated and scored by 3 independent retinal imaging
      experts. The SCP vessel density was assessed using Angiotool-software. After the
      inter-grader reliability assessment, a consensus grading was performed and the
      modules were ranked based on their scoring. RESULTS: There was no significant
      difference in the vessel density among the modules (Zeiss 48.7+/-4%, Optovue
      47.9+/-3%, Topcon 48.3+/-2%, Heidelberg 46.5+/-4%, p = 0.2). The numbers of
      discernible vessel-bifurcations differed significantly on each module (Zeiss 2+/
      0.9 bifurcations, Optovue 2.5+/-1.2, Topcon 1.3+/-0.7 and Heidelberg 0.5+/-0.6,
      p<=0.001). The ranking of each module differed depending on the evaluated
      parameter. In the overall ranking, the Zeiss module was superior and in 90%
      better than the median (Bonferroni corrected p-value = 0.04). Optovue was better
      than the median in 60%, Topcon in 40% and Heidelberg module in 10%, however these
      differences were not statistically significant. CONCLUSION: Each of the four
      evaluated OCT-A modules had particular strengths, which differentiated it from
      their competitors.

PMID- 28489916
TI  - Generational distribution of a Candida glabrata population: Resilient old cells
      prevail, while younger cells dominate in the vulnerable host.
AB  - Similar to other yeasts, the human pathogen Candida glabrata ages when it
      undergoes asymmetric, finite cell divisions, which determines its replicative
      lifespan. We sought to investigate if and how aging changes resilience of C.
      glabrata populations in the host environment. Our data demonstrate that old C.
      glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas
      young cells adhere better to epithelial cell layers. Consequently, virulence of
      old compared to younger C. glabrata cells is enhanced in the Galleria mellonella
      infection model. Electron microscopy images of old C. glabrata cells indicate a
      marked increase in cell wall thickness. Comparison of transcriptomes of old and
      young C. glabrata cells reveals differential regulation of ergosterol and Hog
      pathway associated genes as well as adhesion proteins, and suggests that aging is
      accompanied by remodeling of the fungal cell wall. Biochemical analysis supports
      this conclusion as older cells exhibit a qualitatively different lipid
      composition, leading to the observed increased emergence of fluconazole
      resistance when grown in the presence of fluconazole selection pressure. Older C.
      glabrata cells accumulate during murine and human infection, which is
      statistically unlikely without very strong selection. Therefore, we tested the
      hypothesis that neutrophils constitute the predominant selection pressure in
      vivo. When we altered experimentally the selection pressure by antibody-mediated
      removal of neutrophils, we observed a significantly younger pathogen population
      in mice. Mathematical modeling confirmed that differential selection of older
      cells is sufficient to cause the observed demographic shift in the fungal
      population. Hence our data support the concept that pathogenesis is affected by
      the generational age distribution of the infecting C. glabrata population in a
      host. We conclude that replicative aging constitutes an emerging trait, which is
      selected by the host and may even play an unanticipated role in the transition
      from a commensal to a pathogen state.

PMID- 28489919
TI  - Efficacy and safety of gemcitabine plus docetaxel in Japanese patients with
      unresectable or recurrent bone and soft tissue sarcoma: Results from a single
      institutional analysis.
AB  - BACKGROUND: Combination therapy with gemcitabine and docetaxel has been reported
      to be a good therapeutic strategy for patients with soft tissue sarcoma. The aim
      of the present study was to analyze the efficacy and toxicity of gemcitabine with
      docetaxel in Japanese patients with advanced bone and soft tissue sarcoma.
      PATIENTS AND METHODS: We retrospectively analyzed the effect of gemcitabine and
      docetaxel therapy on overall response, progression-free survival, overall
      survival, and toxicity in 42 patients with bone or soft tissue sarcoma who had
      received the therapy between October 2006 and September 2015, at Tohoku
      University Hospital. RESULTS: The median age was 55 years; 23 patients were men,
      and 19 were women. Eight had bone sarcoma and 34 had soft tissue sarcoma. Forty
      patients (95%) had previously been treated with one or more chemotherapeutic
      regimens. The overall response rate was 6.9% and the disease control rate was
      55%. The median progression-free survival was 2.3 months and the median overall
      survival was 14.3 months. Grade 3 or more neutropenia and febrile neutropenia
      were observed in 74% and 4.8% of all patients, respectively. CONCLUSION: The
      response rate was lower and myelosuppression was more frequently observed than in
      other previous reports. On the other hand, most of toxicities were enough
      manageable. In addition, some patients had long survival with a good response.
      Our study supports the notion that gemcitabine and docetaxel therapy is a good
      therapeutic option for treating patients with advanced soft tissue sarcoma as
      well as bone sarcoma, also in Asian populations.

PMID- 28489920
TI  - A national study of the molecular epidemiology of HIV-1 in Australia 2005-2012.
AB  - INTRODUCTION: Rates of new HIV-1 diagnoses are increasing in Australia, with
      evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing
      impact of migration and travel. The present study aims to define HIV-1 subtype
      diversity patterns and investigate possible HIV-1 transmission networks within
      Australia. METHODS: The Australian Molecular Epidemiology Network (AMEN) HIV
      collaborating sites in Western Australia, South Australia, Victoria, Queensland
      and western Sydney (New South Wales), provided baseline HIV-1 partial pol
      sequence, age and gender information for 4,873 patients who had genotypes
      performed during 2005-2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a
      stringent classification of transmission pairs or clusters (bootstrap >=98%,
      genetic distance <=1.5% from at least one other sequence in the cluster).
      RESULTS: HIV-1 subtype B represented 74.5% of the 4,873 sequences (WA 59%, SA
      68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of
      transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of
      sequences, p = 0.3). Significantly more subtype B clusters were comprised of >=3
      sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and
      significantly more subtype B pairs and clusters were male-only (88% compared to
      53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a
      cluster of any size included; being sequenced in a more recent time period
      (p<0.001), being younger (p<0.001), being male (p = 0.023) and having a B subtype
      (p = 0.02). Being in a larger cluster (>3) was associated with being sequenced in
      a more recent time period (p = 0.05) and being male (p = 0.008). CONCLUSION: This
      nationwide HIV-1 study of 4,873 patient sequences highlights the increased
      diversity of HIV-1 subtypes within the Australian epidemic, as well as
      differences in transmission networks associated with these HIV-1 subtypes. These
      findings provide epidemiological insights not readily available using standard
      surveillance methods and can inform the development of effective public health
      strategies in the current paradigm of HIV prevention in Australia.

PMID- 28489921
TI  - Time trend of neurocysticercosis in children with seizures in a tertiary hospital
      of western Nepal.
AB  - INTRODUCTION: Neurocysticercosis is a common cause of seizure disorders in
      children of Western Nepal. The clinical presentation is variable. The incidence
      varies depending on the food habits and ethnicity of the population. The present
      study was undertaken with the objective of studying the mode of presentation,
      radiological findings and to determine the recent trend of the disease in
      children of Western Nepal. METHODS: Records from the Department of Pediatrics,
      Manipal Teaching Hospital, Pokhara, Nepal of children aged 0-17 years admitted
      from 2003 to 2015 and with the discharge diagnosis of seizure and
      neurocysticercosis (NCC) were reviewed. The diagnosis was primarily based on
      clinical features, neurological involvement and CT and MRI studies. Seizures due
      to other CNS pathologies were excluded. Patients with NCC were treated with
      Albendazole15mg/kg/day for 28 days with supportive treatments for seizures and
      raised intracranial pressure. Patients were followed up for one year after the
      completion of the treatment. RESULTS: There were 1355 cases of seizure disorders,
      out of which 229 (16.90%) were NCC. There were 99 (43.23%) in the age group 6-10
      years followed by 91 (41.09%) in the age group of 11-15 years. Seizures were the
      most common presenting symptom in 88.65%, followed by raised ICP in 9.61%.
      Neuropsychiatric changes were noted in 38 cases (16.59%). CT scan findings
      revealed single lesion in 78.16% and multiple lesions in 21.83%. Poisson
      regression analysis showed statistically significant decline of year-wise
      incidence of NCC cases (p<0.05) from 2003 to 2015. CONCLUSION: The decline in the
      incidence of NCC in recent years is most probably attributed to improved hygiene
      with the construction of household toilets to avoid open defecation and biannual
      deworming with Albendazole as a part of School Health and Nutrition Project.

PMID- 28489922
TI  - Contribution of thrombin-reactive brain pericytes to blood-brain barrier
      dysfunction in an in vivo mouse model of obesity-associated diabetes and an in
      vitro rat model.
AB  - Diabetic complications are characterized by the dysfunction of pericytes located
      around microvascular endothelial cells. The blood-brain barrier (BBB) exhibits
      hyperpermeability with progression of diabetes. Therefore, brain pericytes at the
      BBB may be involved in diabetic complications of the central nervous system
      (CNS). We hypothesized that brain pericytes respond to increased brain thrombin
      levels in diabetes, leading to BBB dysfunction and diabetic CNS complications.
      Mice were fed a high-fat diet (HFD) for 2 or 8 weeks to induce obesity. Transport
      of i.v.-administered sodium fluorescein and 125I-thrombin across the BBB were
      measured. We evaluated brain endothelial permeability and expression of tight
      junction proteins in the presence of thrombin-treated brain pericytes using a BBB
      model of co-cultured rat brain endothelial cells and pericytes. Mice fed a HFD
      for 8 weeks showed both increased weight gain and impaired glucose tolerance. In
      parallel, the brain influx rate of sodium fluorescein was significantly greater
      than that in mice fed a normal diet. HFD feeding inhibited the decline in brain
      thrombin levels occurring during 6 weeks of feeding. In the HFD fed mice, plasma
      thrombin levels were significantly increased, by up to 22%. 125I-thrombin was
      transported across the BBB in normal mice after i.v. injection, with uptake
      further enhanced by co-injection of unlabeled thrombin. Thrombin-treated brain
      pericytes increased brain endothelial permeability and caused decreased
      expression of zona occludens-1 (ZO-1) and occludin and morphological
      disorganization of ZO-1. Thrombin also increased mRNA expression of interleukin
      1beta and 6 and tumor necrosis factor-alpha in brain pericytes. Thrombin can be
      transported from circulating blood through the BBB, maintaining constant levels
      in the brain, where it can stimulate pericytes to induce BBB dysfunction. Thus,
      the brain pericyte-thrombin interaction may play a key role in causing BBB
      dysfunction in obesity-associated diabetes and represent a therapeutic target for
      its CNS complications.

PMID- 28489924
TI  - Neonatal and maternal outcomes of successful manual rotation to correct
      malposition of the fetal head; A retrospective and prospective observational
      study.
AB  - OBJECTIVE: To evaluate the neonatal and maternal outcomes associated with
      successful operative vaginal births assisted by manual rotation. DESIGN:
      Prospective and retrospective observational study. SETTING: Delivery suite in a
      tertiary referral teaching hospital in England. POPULATION: A cohort of 2,426
      consecutive operative births, in the second stage of labour, complicated with
      malposition of the fetal head during 2006-2013. METHODS: Outcomes of all births
      successfully assisted by manual rotation followed by direct traction instruments
      were compared with other methods of operative birth for fetal malposition in the
      second stage of labour (rotational ventouse, Kielland forceps and caesarean
      section). MAIN OUTCOME MEASURES: Associated neonatal outcomes (admission to the
      special care baby unit, low cord pH, low Apgar and shoulder dystocia) and
      maternal outcomes (massive obstetric haemorrhage (blood loss of >1500ml) and
      obstetric anal sphincter injury). RESULTS: Births successfully assisted with
      manual rotation followed by direct traction instruments, resulted in 10% (36/346)
      of the babies being admitted to the Special Care Baby Unit, 4.9% (17/349)
      shoulder dystocia, 2% (7/349) massive obstetric haemorrhage and 1.7% (6/349)
      obstetric anal sphincter injury, similar to other methods of rotational births.
      CONCLUSIONS: Adverse neonatal and maternal outcomes associated with successful
      manual rotations followed by direct traction instruments were comparable to
      traditional methods of operative births. There is an urgent need to standardise
      the practice (guidance, training) and documentation of manual rotation followed
      by direct traction instrumental deliveries that will enable assessment of its
      efficacy and the absolute safety in achieving a vaginal birth.

PMID- 28489925
TI  - Do the Brazilian sardine commercial landings respond to local ocean circulation?
AB  - It has been reported that sea surface temperature (SST) anomalies, flow intensity
      and mesoscale ocean processes, all affect sardine production, both in eastern and
      western boundary current systems. Here we tested the hypothesis whether extreme
      high and low commercial landings of the Brazilian sardine fisheries in the South
      Brazil Bight (SBB) are sensitive to different oceanic conditions. An ocean model
      (ROMS) and an individual based model (Ichthyop) were used to assess the
      relationship between oceanic conditions during the spawning season and commercial
      landings of the Brazilian sardine one year later. Model output was compared with
      remote sensing and analysis data showing good consistency. Simulations indicate
      that mortality of eggs and larvae by low temperature prior to maximum and minimum
      landings are significantly higher than mortality caused by offshore advection.
      However, when periods of maximum and minimum sardine landings are compared with
      respect to these causes of mortality no significant differences were detected.
      Results indicate that mortality caused by prevailing oceanic conditions at early
      life stages alone can not be invoked to explain the observed extreme commercial
      landings of the Brazilian sardine. Likely influencing factors include starvation
      and predation interacting with the strategy of spawning "at the right place and
      at the right time".

PMID- 28489923
TI  - Differences of microparticle patterns between sickle cell anemia and hemoglobin
      SC patients.
AB  - Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common
      forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a
      highly variable clinical course. Although high levels of microparticles (MPs)
      have been consistently reported in SCA and evidence of their harmful impact on
      the SCA complication occurrences have been provided, no data on MP pattern in
      HbSC patients has been reported so far. In this study, we determined and compared
      the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow
      cytometry. Most of circulating MPs were derived from platelets (PLTs) and red
      blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC
      patients exhibited lower blood concentration of total MPs compared to SCA
      patients, resulting mainly from a decrease of MP levels originated from RBCs and
      to a lesser extent from PLTs. We did not detect any association between blood MP
      concentrations and the occurrence of painful vaso-occlusive crises, acute chest
      syndrome and pulmonary hypertension in both patient groups. We also demonstrated
      for the first time, that whatever the considered genotype, RBC-derived MPs
      exhibited higher externalized phosphatidylserine level and were larger than PLT
      derived MPs.

PMID- 28489926
TI  - Moving beyond pain scores: Multidimensional pain assessment is essential for
      adequate pain management after surgery.
AB  - BACKGROUND: Clinical experience teaches us that patients are willing to accept
      postoperative pain, despite high pain intensity scores. Nevertheless,
      relationships between pain scores and other methods of pain assessment, e.g.
      acceptability of pain or its interference with physical functioning, are not
      fully established. Our aims were to examine these relationships. METHODS: A cross
      sectional study was conducted on patients who underwent major surgery between
      January 2008 and August 2013. Using logistic regression, we quantified the
      relationships between movement-evoked pain scores on the numerical rating scale
      (NRS-MEP) and three dichotomous dependent variables: patient's opinion on
      acceptability of pain (PO: acceptable or unacceptable pain); nurses' observation
      of patient's performance of necessary activities to expedite recovery (NO: good
      or bad performance); a compound measure judging the presence of the clinically
      desirable situation of acceptable pain associated with good patients' performance
      (PONO: present or not). Using Receiver Operating Characteristics (ROC) analysis,
      NRS cut-off points were determined such that they best discriminate between
      patients having one versus the other outcome for PO, NO and PONO. RESULTS: 15,394
      assessments were obtained in 9,082 patients in the first three postoperative
      days. Nine percent of the patients had unacceptable pain while having an NRS-MEP
      of 0-4. An estimated 47% (95%CI = 45%-49%) of patients with an NRS-MEP of 7
      described their pain as acceptable on day one. Moreover, 33% (31%-35%) performed
      all required physical activities, and 22% (21%-24%) combined acceptable pain with
      appropriate movement. NRS cut-off points for PO, NO and PONO were five, four and
      four, respectively, but had insufficient discriminatory power. CONCLUSIONS: Our
      results suggest pain management should be guided by the many dimensions of the
      patient's pain experience, not solely by NRS cut-off points. Future research
      should evaluate the impact of such multidimensional pain assessment on patients'
      functional outcome.

PMID- 28489927
TI  - Protein degradation rate is the dominant mechanism accounting for the differences
      in protein abundance of basal p53 in a human breast and colorectal cancer cell
      line.
AB  - We determine p53 protein abundances and cell to cell variation in two human
      cancer cell lines with single cell resolution, and show that the fractional width
      of the distributions is the same in both cases despite a large difference in
      average protein copy number. We developed a computational framework to identify
      dominant mechanisms controlling the variation of protein abundance in a simple
      model of gene expression from the summary statistics of single cell steady state
      protein expression distributions. Our results, based on single cell data analysed
      in a Bayesian framework, lends strong support to a model in which variation in
      the basal p53 protein abundance may be best explained by variations in the rate
      of p53 protein degradation. This is supported by measurements of the relative
      average levels of mRNA which are very similar despite large variation in the
      level of protein.

PMID- 28489929
TI  - A content analysis of nature photographs taken by Lebanese rural youth.
AB  - 'Living in Harmony with Nature' is a 2050 vision put forth by the Convention on
      Biological Diversity (CBD) which takes into consideration culture and locality of
      perceptions of nature and aspirations for its use. Considering that 54% of the
      world population lives in cities, where nature has been decimated, the role of
      rural communities, living within or in proximity of natural and semi natural
      areas, will effectively influence the fate of the 'remaining' nature while they
      engage in local development. Reconciling between growth and development on the
      one hand, and nature conservation on the other, necessitates an understanding of
      how rural communities, especially the youth, imprint their own ideas on
      landscapes and develop ownership over natural spaces. In order to extend the
      understanding of how harmony with nature is perceived in different parts of the
      world, this paper presents the findings of primary research involving a group of
      young people who live in rural areas in Lebanon, a country in the Arab Middle
      East. Participatory research based on photovoice methodology was conducted with
      77 young people aged 7-16 and residing in five rural villages located in
      different parts of Lebanon. Photographs taken by participants indicated that for
      many, nature was not perceived literally i.e. woodlands, forests, plants,
      animals, etc.... Instead, the participants saw nature as part of agriculture and
      local culture. Nature was also seen as symbolic expression of the participants'
      inner state of mind. Narratives written to explain the photographs shed light on
      the perception of harmony with nature which focused on positive family
      experiences and relayed personal emotions, abstract, and holistic yet functional
      view of nature. Another recurring theme that emerged from photographs and
      narratives was the role of family members, in particular grandparents, as having
      a strong influence on the positive perceptions of nature.

PMID- 28489928
TI  - Identification and analysis of the beta-catenin1 gene in half-smooth tongue sole
      (Cynoglossus semilaevis).
AB  - beta-catenin is a key signalling molecule in the canonical Wnt pathway, which
      plays a role in cell adhesion, embryogenesis and sex determination. However,
      little is known about its function in teleosts. We cloned and characterized the
      full-length beta-catenin1 gene from half-smooth tongue sole (Cynoglossus
      semilaevis), which was designated CS-beta-catenin1. The CS-beta-catenin1 cDNA
      consists of 2,346 nucleotides and encodes a protein with 782 amino acids.
      Although CS-beta-catenin1 was transcribed in the gonads of both sexes, the level
      was significantly higher in ovaries compared to testes. Furthermore, the mRNA
      level of CS-beta-catenin1 was significantly upregulated at 160 days and
      constantly increased until 2 years of age. In situ hybridization revealed that CS
      beta-catenin1 mRNA was mainly localized in oocyte cells, especially in stage I,
      II and III oocytes. When CS-beta-catenin1 expression was inhibited by injection
      of quercetin in the ovaries, levels of CS-Figla and CS-foxl2 mRNA were
      significantly down-regulated, and CS-dmrt1 was up-regulated, which suggested that
      CS-beta-catenin1 is a potential upstream gene of CS-Figla and is involved in the
      development of the ovaries, i.e., folliculogenesis.

PMID- 28489930
TI  - Prognostic value of cervical nodal tumor volume in nasopharyngeal carcinoma:
      Analysis of 1230 patients with positive cervical nodal metastasis.
AB  - PURPOSE: To investigate the variability and prognostic value of nodal tumor
      volume (NTV) in nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Data on
      1230 patients with newly diagnosed stage T1-4N1-3M0 NPC treated with definitive
      radiation therapy with or without chemotherapy at a single cancer center were
      reviewed. NTV was determined from dose volume histogram (DVH) data. X-tile
      analysis was applied to identify the optimal cut-off points for the NTV with
      respect to regional recurrence-free survival (RRFS). Correlations between the TNM
      classification system, NTV and RRFS were assessed using a Cox regression model.
      Cross-validation based on receiver operating characteristic (ROC) curve analysis
      was applied to compare the prognostic predictive validity of NTV and N
      categories. RESULTS: Within a median follow-up of 49.9 (range, 1.27-76.40)
      months, 61/1230 (5%) patients developed regional recurrence and 154 (12.5%)
      developed distant metastasis. NTV values of 7.2 cc and 35.7 cc were identified as
      the optimal cut-off points. Patients with larger NTV had poorer prognosis.
      Compared with the N category, NTV was better at determining RRFS for patients
      with NPC. Hazard ratios increased with NTV, ranging from 1.86 (95% confidence
      interval [95% CI], 0.92-3.78) for NTV between 7.2 cc to 35.7 cc, and 3.67 (95%
      CI, 1.58-8.50) for NTV > 35.7 cc. With both NTV and N category in the same Cox
      regression model, only NTV remained statistically significant in the RRFS of NPC.
      The validation results with ROC curves also revealed that, NTV was superior to N
      category for predicting RRFS with significantly larger area under the ROC curve.
      CONCLUSIONS: NTV offers important prognostic value for treatment outcomes in NPC,
      especially regional control. Volumetric analysis of nodal involvement may assist
      selection of patients with poor prognosis.

PMID- 28489931
TI  - Cortical involvement in celiac disease before and after long-term gluten-free
      diet: A Transcranial Magnetic Stimulation study.
AB  - OBJECTIVE: Transcranial Magnetic Stimulation in de novo patients with Celiac
      Disease previously revealed an imbalance in the excitability of cortical
      facilitatory and inhibitory circuits. After a median period of 16 months of
      gluten-free diet, a global increase of cortical excitability was reported,
      suggesting a glutamate-mediated compensation for disease progression. We have now
      evaluated cross-sectionally the changes of cortical excitability to TMS after a
      much longer gluten-free diet. METHODS: Twenty patients on adequate gluten-free
      diet for a mean period of 8.35 years were enrolled and compared with 20 de novo
      patients and 20 healthy controls. Transcranial Magnetic Stimulation measures,
      recorded from the first dorsal interosseous muscle of the dominant hand,
      consisted of: resting motor threshold, cortical silent period, motor evoked
      potentials, central motor conduction time, mean short-latency intracortical
      inhibition and intracortical facilitation. RESULTS: The cortical silent period
      was shorter in de novo patients, whereas in gluten-free diet participants it was
      similar to controls. The amplitude of motor responses was significantly smaller
      in all patients than in controls, regardless of the dietary regimen.
      Notwithstanding the diet, all patients exhibited a statistically significant
      decrease of mean short-latency intracortical inhibition and enhancement of
      intracortical facilitation with respect to controls; more intracortical
      facilitation in gluten-restricted compared to non-restricted patients was also
      observed. Neurological examination and celiac disease-related antibodies were
      negative. CONCLUSIONS: In this new investigation, the length of dietary regimen
      was able to modulate the electrocortical changes in celiac disease. Nevertheless,
      an intracortical synaptic dysfunction, mostly involving excitatory and inhibitory
      interneurons within the motor cortex, may persist. The clinical significance of
      subtle neurophysiological changes in celiac disease needs to be further
      investigated.

PMID- 28489933
TI  - A practical model for the train-set utilization: The case of Beijing-Tianjin
      passenger dedicated line in China.
AB  - As a sustainable transportation mode, high-speed railway (HSR) has become an
      efficient way to meet the huge travel demand. However, due to the high
      acquisition and maintenance cost, it is impossible to build enough infrastructure
      and purchase enough train-sets. Great efforts are required to improve the
      transport capability of HSR. The utilization efficiency of train-sets (carrying
      tools of HSR) is one of the most important factors of the transport capacity of
      HSR. In order to enhance the utilization efficiency of the train-sets, this paper
      proposed a train-set circulation optimization model to minimize the total
      connection time. An innovative two-stage approach which contains segments
      generation and segments combination was designed to solve this model. In order to
      verify the feasibility of the proposed approach, an experiment was carried out in
      the Beijing-Tianjin passenger dedicated line, to fulfill a 174 trips train
      diagram. The model results showed that compared with the traditional Ant Colony
      Algorithm (ACA), the utilization efficiency of train-sets can be increased from
      43.4% (ACA) to 46.9% (Two-Stage), and 1 train-set can be saved up to fulfill the
      same transportation tasks. The approach proposed in the study is faster and more
      stable than the traditional ones, by using which, the HSR staff can draw up the
      train-sets circulation plan more quickly and the utilization efficiency of the
      HSR system is also improved.

PMID- 28489932
TI  - CaMKIIalpha may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal
      cord descending facilitative pain pathway in rats.
AB  - Each of the lateral capsular division of central nucleus of amygdala(CeLC),
      periaqueductal gray (PAG), rostral ventromedial medulla(RVM) and spinal cord has
      been proved to contribute to the development of opioid-induced hyperalgesia(OIH).
      Especially, Ca2+/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) in
      CeLC and spinal cord seems to play a key role in OIH modulation. However, the
      pain pathway through which CaMKIIalpha modulates OIH is not clear. The pathway
      from CeLC to spinal cord for this modulation was explored in the present study.
      Mechanical and thermal hyperalgesia were tested by von Frey test or Hargreaves
      test, respectively. CaMKIIalpha activity (phospho-CaMKIIalpha, p-CaMKIIalpha) was
      evaluated by western blot analysis. CaMKIIalpha antagonist (KN93) was micro
      infused into CeLC, spinal cord or PAG, respectively, to evaluate its effect on
      behavioral hyperalgesia and p-CaMKIIalpha expression in CeLC, PAG, RVM and spinal
      cord. Then the underlying synaptic mechanism was explored by recording miniature
      excitatory postsynaptic currents (mEPSCs) on PAG slices using whole-cell voltage
      clamp methods. Results showed that inhibition of CeLC, PAG or spinal CaMKIIalpha
      activity respectively by KN93, reversed both mechanical and thermal hyperalgesia.
      Microinjection of KN93 into CeLC decreased p-CaMKIIalpha expression in CeLC, PAG,
      RVM and spinal cord; while intrathecal KN93 can only block spinal but not CeLC
      CaMKIIalpha activity. KN93 injected into PAG just decreased p-CaMKIIalpha
      expression in PAG, RVM and spinal cord, but not in the CeLC. Similarly, whole
      cell voltage-clamp recording found the frequency and amplitude of mEPSCs in PAG
      cells were decreased by KN93 added in PAG slice or micro-infused into CeLC in
      vivo. These results together with previous findings suggest that CaMKIIalpha may
      modulate OIH via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway.

PMID- 28489934
TI  - Genetic pattern and gene localization of polydactyly in Beijing fatty chicken.
AB  - Polydactyly, a common heritable limb malformation in vertebrates, is
      characterized by supernumerary digits. In chickens, basic characteristics and
      rough dominant genes have been explored in past decades; however, the elaborate
      pattern of inheritance and the determinant gene remain obscure. In this study,
      different types of polydactylism were classified by the numbers and the shapes of
      toes, including the newly defined subtypes of B' and G, for the Beijing fatty
      chicken, a native breed of chicken from China. Through experiments on
      hybridization, we demonstrated a complete dominant inheritance of polydactyly
      instead of an incomplete penetrance or genetic modification of the previous
      conjecture. In particular, by using the F2 population of the five-digit purebred
      line of Beijing fatty chicken backcrossed to Shiqiza chicken and by using
      restriction-site associated DNA based markers, we performed a genome-wide
      association study on the trait of polydactyly. Furthermore, whole genome
      resequencing strategy was applied to sweep SNPs across the whole genome. An
      outlier-based Fst approach was employed to search for signatures of selection,
      and results indicated that the determinant mutation was found in the region
      ranging from 8.3 Mb to 8.7 Mb, where the polydactyly candidate gene LMBR1 was
      located. The G/T mutation of rs80659072 was identified to be highly associated
      with polydactyly in our resequencing and was validated in random samples from an
      expanded population. Thus, we confirmed that LMBR1 was the causative gene of
      polydactyly in the Beijing fatty chicken by using GWAS with restriction-site
      associated DNA based markers and resequencing.

PMID- 28489935
TI  - Indoor residual spraying with micro-encapsulated pirimiphos-methyl (Actellic(r)
      300CS) against malaria vectors in the Lake Victoria basin, Tanzania.
AB  - BACKGROUND: The indoor residual spraying programme for malaria vectors control
      was implemented in four districts of the Lake Victoria basin of Tanzania namely
      Ukerewe, Sengerema, Rorya andSerengeti. Entomological monitoring activities were
      implemented in one sentinel village in each district to evaluate the efficacy of
      pirimiphos-methyl 300 CS sprayed on different wall surfaces and its impact
      against malaria vectors post-IRS intervention. METHODS: The residual decay rate
      of p-methyl 300 CS applied at a target dosage of 1g a.i./m2 on thesprayed wall
      surfaces was monitored for a period of 43 weeks post-IRSusing the WHO cone wall
      bioassay method. The bioassays were performed by exposing 2-5 days old unfed
      susceptible female Anopheles gambiae s.s. (Kisumu strain) to sprayed wall
      surfaces for a period of 30 minutes. In each sentinel village, mosquito
      collection was carried out by trained community mosquito collectors. Monthly
      mosquito collections were carried out from 6.00pm to 6.00am using CDC light traps
      and clay pot methods for indoors host seekingand outdoors resting mosquitoes
      respectively. Six traps (2 CDC light traps and 4 clay pots) were set per sentinel
      village per night for28 consecutive days in a moon. PCR and ELISA were used for
      mosquito species identification and sporozoite detection, respectively. RESULTS:
      Based on the WHOPES recommendation, insecticides should have a minimum efficacy
      of >= 80% mosquito mortality at 24 hours post exposure on the sprayed wall
      surfaces to be considered effective. In this study, p-methyl 300 CS was
      demonstrated to have a long residual efficacy of 21-43 weeks post-IRS on mud,
      cement, painted and wood wall surfaces. Numberof anopheline mosquitoes decreased
      post-IRS interventions in all sentinel villages. The highest numbers ofanopheline
      mosquitoes were collected in November-December, 38-43 weeks post-IRS. A total of
      270 female anopheline mosquitoes were analyzed by PCR; out of which 236 (87.4%)
      were An. gambiae s.l. and 34 (12.6%) were An. funestus group. Of the 236 An.
      gambiae s.l.identified 12.6% (n = 34) were An. gambiae s.s. and 68.6% (n = 162)
      were An. arabiensis. Ofthe 34 An. funestus group indentified 91.2% (n = 31) were
      An. parensis and 8.8% (n = 3) were An. rivulorum. The overall Plasmodium
      falciparum sporozoite rate was 0.7% (n = 2,098). CONCLUSIONS: Pirimiphos-methyl
      300 CS was found to be effective for IRS in the Lake Victoria basin,Tanzania. P
      methyl 300 CShas a long residual efficacy on sprayed wall surfaces and therefore
      it is effective in controlling principal malaria vectors of An. gambiae s.l and
      An. funestus which rest on wall surfaces after and before feeding.

PMID- 28489936
TI  - The association of dietary vitamin C intake with periodontitis among Korean
      adults: Results from KNHANES IV.
AB  - BACKGROUNDS: The association of dietary vitamin C (vit C) on periodontitis
      requires more valid evidence from large representative samples to enable
      sufficient adjustments. This study aimed to evaluate the association between
      dietary vit C intake and periodontitis after controlling for various confounders
      in the representative Korean adult population. METHOD: A total of 10,930 Korean
      adults (>=19 years) from the fourth Korean National Health and Nutrition
      Examination Survey data set were included in this cross-sectional study.
      Periodontitis was defined as community periodontal index score of 3 or 4. Dietary
      vit C intake was estimated from a 24-hour dietary record, and categorized into
      adequate and inadequate according to the Korean Estimated Average Requirement
      value. Potential confounders included age, sex, income, frequency of tooth
      brushing, use of floss, dental visit, drinking, smoking, diabetes,
      hypercholesterolemia, hypertension, and obesity. A multivariable logistic
      regression analysis and stratified analysis were applied. RESULTS: Those with
      inadequate dietary vit C intake were more likely by 1.16 times to have
      periodontitis than those with adequate dietary vit C intake (adjusted odds ratio
      [aOR] = 1.16, 95% confidence interval = 1.04-1.29). Lowest and middle-low
      quartile of dietary vit C intake, compared to highest quartile of dietary vit C
      intake, showed significant association (aOR = 1.28 and 1.22 respectively), which
      was in a biological-gradient relationship (trend-p <0.05). CONCLUSIONS: Our data
      showed that inadequate dietary vit C intake was independently associated with
      periodontitis among Korean adults. Hence, adequate intake of dietary vitamin C
      could be substantially important on the promotion of periodontal health among
      Korean adults.

PMID- 28489937
TI  - Impact of sublethal exposure to a pyrethroid-neonicotinoid insecticide on mating,
      fecundity and development in the bed bug Cimex lectularius L. (Hemiptera:
      Cimicidae).
AB  - Sublethal exposure to an insecticide may alter insect feeding, mating,
      oviposition, fecundity, development, and many other life history parameters. Such
      effects may have population-level consequences that are not apparent in
      traditional dose-mortality evaluations. Earlier, we found that a routinely used
      combination insecticide that includes a pyrethroid and a neonicotinoid
      (Temprid(r) SC) had deleterious effects on multiple bed bug (Cimex lectularius,
      L.) behaviors. Here, we demonstrate that sublethal exposure impacts physiology
      and reproduction as well. We report that sublethal exposure to Temprid SC has
      variable aberrant effects on bed bugs depending on the strain, including: a
      reduction in male mating success and delayed oviposition by females. However,
      after sublethal exposure, egg hatch rate consistently declined in every strain
      tested, anywhere from 34%-73%. Conversely, impact on fifth instar eclosion time
      was not significant. While the strains that we tested varied in their respective
      magnitude of sublethal effects, taken together, these effects could reduce bed
      bug population growth. These changes in bed bug behavior and fecundity could lead
      to improved efficacy of Temprid SC in the field, but recovery of impacted bugs
      must be considered in future studies. Sublethal effects should not be overlooked
      when evaluating insecticide efficacy, as it is likely that other products may
      also have indirect effects on population dynamics that could either aid or
      inhibit successful management of pest populations.

PMID- 28489938
TI  - Metabolites contributing to Rhizoctonia solani AG-1-IA maturation and sclerotial
      differentiation revealed by UPLC-QTOF-MS metabolomics.
AB  - Rhizoctonia solani is a causative agent of sheath blight, which results in huge
      economic losses every year. During its life cycle, the formation of sclerotia
      helps Rhizoctonia solani withstand a variety of unfavorable factors. Oxidative
      stress is a key factor that induces sclerotium formation. The differentiated and
      undifferentiated phenotypes of R. solani AG-1-IA were obtained by controlling
      aerial conditions. Metabolomics based on the mass spectrometry technique combined
      with multivariate and univariate analyses was used to investigate the metabolic
      variation in vegetative, differentiated and undifferentiated mycelia. Our results
      revealed that during maturation, the metabolic levels of N2-acetyl-L-ornithine,
      3,1'-(OH)2-Gamma-carotene, (5Z,7E)-(1S,3R)-24,24-difluoro-24a-homo-9,10-seco
      5,7,10(19)-cholestatrien-1,3,25-triol, stoloniferone O, PA(O-18:0/12:0), PA(P
      16:0/14:0), PA(P-16:0/16:(19Z)) and PA(P-16:0/17:2(9Z,12Z)) were suppressed in
      both differentiated and undifferentiated mycelia. The concentrations of
      PE(20:1(11Z)/14:1(9Z)), PE(P-16:0/20:4(5Z,8Z,11Z,13E)(15OH[S])) and
      PS(12:0/18:1(9Z)) were increased in the differentiated group, while increased
      levels of N(gamma)-nitro-L-arginine, tenuazonic acid and 9S,10S,11R-trihydroxy
      12Z,15Z-octadecadienoic acid were found in the undifferentiated group. Our
      results suggest that different levels of these metabolites may act as biomarkers
      for the developmental stages of R. solani AG-1-IA. Moreover, the mechanisms of
      sclerotium formation and mycelium differentiation were elucidated at the
      metabolic level.

PMID- 28489939
TI  - Prevalence of chronic stress in general practitioners and practice assistants:
      Personal, practice and regional characteristics.
AB  - BACKGROUND: The majority of studies investigating stress in primary care have
      focused either on general practitioners (GPs) or practice assistants (PAs), but
      did not measure stress on a practice level. We analyzed the prevalence of chronic
      stress for both professional groups and on a practice level and investigated
      personal, practice, and regional characteristics. METHODS: Chronic stress was
      measured in GPs and PAs from 136 German practices using the standardized, self
      administered TICS-SSCS questionnaire (12 items). Based on a sum-score,
      participants per professional group were categorized as having low or high strain
      due to chronic stress (<= 25th and >= 75th percentile of the study population's
      distribution, respectively). For a cluster-level analysis, the mean of all
      practice means was used to categorize low- and high-stress practices. The intra
      class correlation coefficient (ICC) was calculated using ANOVA. Prevalence Ratios
      (PR) were used to compare low versus high strain due to stress, stratified for
      personal, practice and regional characteristics. RESULTS: The response rate was
      74.1% (n = 137/185). Data from 214 GPs (34.1% female), 500 PAs (99.4% female),
      and 50 PAs in training (98.0% female) were analyzed. Chronic stress was highest
      in female GPs (median 19, IQR (interquartile range) 11.5), followed by PAs (16,
      IQR 12.25) and male GPs (15, IQR 10). On a practice level, 26.3% of the practice
      personnel reported a high stress level. We observed an overall ICC of 0.25, with
      higher ICCs when stratifying by professional group (PAs: ICC 0.36, GPs in group
      practices: ICC 0.51). High chronic stress was observed as the number of working
      hours per week increased (GPs: PR 2.03, 95% CI 1.16-3.56; PAs: PR 2.02, 95% CI
      1.22-3.35). There were no differences for practice type (solo/group) and the
      various regional characteristics. CONCLUSION: Personal and practice
      characteristics were associated with chronic stress in GPs, PAs, and on a
      practice level. The high ICCs indicate a need for stress-reduction strategies
      geared at both professions on a practice level.

PMID- 28489941
TI  - Triboelectric Nanogenerator Enhanced Nanofiber Air Filters for Efficient
      Particulate Matter Removal.
AB  - We developed a high-efficiency rotating triboelectric nanogenerator (R-TENG)
      enhanced polyimide (PI) nanofiber air filter for particulate matter (PM) removal
      in ambient atmosphere. The PI electrospinning nanofiber film exhibited high
      removal efficiency for the PM particles that have diameters larger than 0.5 MUm.
      When the R-TENG is connected, the removal efficiency of the filter is enhanced,
      especially when the particle diameters of the PM are smaller than 100 nm. The
      highest removal efficiency is 90.6% for particles with a diameter of 33.4 nm and
      the highest efficiency enhancement reaches 207.8% at the diameter of 76.4 nm
      where the removal efficiency enhanced from 27.1% to 83.6%. This technology with
      zero ozone release and low pressure drop offers an approach for air cleaning and
      haze treatment.

PMID- 28489942
TI  - Biotunable Nanoplasmonic Filter on Few-Layer MoS2 for Rapid and Highly Sensitive
      Cytokine Optoelectronic Immunosensing.
AB  - Monitoring of the time-varying immune status of a diseased host often requires
      rapid and sensitive detection of cytokines. Metallic nanoparticle-based localized
      surface plasmon resonance (LSPR) biosensors hold promise to meet this clinical
      need by permitting label-free detection of target biomolecules. These biosensors,
      however, continue to suffer from relatively low sensitivity as compared to
      conventional immunoassay methods that involve labeling processes. Their response
      speeds also need to be further improved to enable rapid cytokine quantification
      for critical care in a timely manner. In this paper, we report an
      immunobiosensing device integrating a biotunable nanoplasmonic optical filter and
      a highly sensitive few-layer molybdenum disulfide (MoS2) photoconductive
      component, which can serve as a generic device platform to meet the need of rapid
      cytokine detection with high sensitivity. The nanoplasmonic filter consists of
      anticytokine antibody-conjugated gold nanoparticles on a SiO2 thin layer that is
      placed 170 MUm above a few-layer MoS2 photoconductive flake device. The principle
      of the biosensor operation is based on tuning the delivery of incident light to
      the few-layer MoS2 photoconductive flake thorough the nanoplasmonic filter by
      means of biomolecular surface binding-induced LSPR shifts. The tuning is
      dependent on cytokine concentration on the nanoplasmonic filter and
      optoelectronically detected by the few-layer MoS2 device. Using the developed
      optoelectronic biosensor, we have demonstrated label-free detection of IL-1beta,
      a pro-inflammatory cytokine, with a detection limit as low as 250 fg/mL (14 fM),
      a large dynamic range of 106, and a short assay time of 10 min. The presented
      biosensing approach could be further developed and generalized for point-of-care
      diagnosis, wearable bio/chemical sensing, and environmental monitoring.

PMID- 28489940
TI  - Isolation and characterization of canine perivascular stem/stromal cells for bone
      tissue engineering.
AB  - For over 15 years, human subcutaneous adipose tissue has been recognized as a
      rich source of tissue resident mesenchymal stem/stromal cells (MSC). The
      isolation of perivascular progenitor cells from human adipose tissue by a cell
      sorting strategy was first published in 2008. Since this time, the interest in
      using pericytes and related perivascular stem/stromal cell (PSC) populations for
      tissue engineering has significantly increased. Here, we describe a set of
      experiments identifying, isolating and characterizing PSC from canine tissue (N =
      12 canine adipose tissue samples). Results showed that the same antibodies used
      for human PSC identification and isolation are cross-reactive with canine tissue
      (CD45, CD146, CD34). Like their human correlate, canine PSC demonstrate
      characteristics of MSC including cell surface marker expression, colony forming
      unit-fibroblast (CFU-F) inclusion, and osteogenic differentiation potential. As
      well, canine PSC respond to osteoinductive signals in a similar fashion as do
      human PSC, such as the secreted differentiation factor NEL-Like Molecule-1 (NELL
      1). Nevertheless, important differences exist between human and canine PSC,
      including differences in baseline osteogenic potential. In summary, canine PSC
      represent a multipotent mesenchymogenic cell source for future translational
      efforts in tissue engineering.

PMID- 28489943
TI  - Reduced Single Nucleotide Polymorphism Panels for Assigning Atlantic Albacore and
      Bay of Biscay Anchovy Individuals to Their Geographic Origin: Toward Sustainable
      Fishery Management.
AB  - There is an increasing trend upon adding a detailed description of the origin of
      seafood products driven by a general interest in the implementation of
      sustainable fishery management plans for the conservation of marine ecosystems.
      North Atlantic albacore ("Bonito del Norte con Eusko Label") and Bay of Biscay
      anchovy ("Anchoa del Cantabrico") are two commercially important fish populations
      with high economical value and vulnerable to commercial fraud. This fact,
      together with the overexploited situation of these two populations, makes it
      necessary to develop a tool to identify individual origin and to detect
      commercial fraud. In the present study, we have developed and validated a
      traceability tool consisting of reduced panels of gene-associated single
      nucleotide polymorphisms (SNPs) suitable for assigning individuals of two species
      to their origin with unprecedented accuracy levels. Only 48 SNPs are necessary to
      assign 81.1% albacore and 93.4% anchovy individuals with 100% accuracy to their
      geographic origin. The total accuracy of the results demonstrates how gene
      associated SNPs can revolutionize food traceability. Gene-associated SNP panels
      are not of mere commercial interest, but they also can result in a positive
      impact on sustainability of marine ecosystems through conservation of fish
      populations through establishing a more effective and sustainable fishery
      management framework and contributing to the prevention of falsified labeling.

PMID- 28489944
TI  - Studying the Crystallization of Various Polymorphic Forms of Nifedipine from
      Binary Mixtures with the Use of Different Experimental Techniques.
AB  - In this paper the crystal growth of nifedipine from pure system and from binary
      mixtures composed of active substance (API) and two acetylated disaccharides,
      maltose and sucrose (NIF-acMAL, NIF-acSUC, 5:1 weight ratio), was investigated.
      Optical snapshots supported by X-ray diffraction (XRD) and Fourier transform
      infrared spectroscopy (FTIR) measurements showed that mainly beta and alpha forms
      of nifedipine grow up in all investigated samples. They also revealed that the
      morphology of growing crystals strongly depends on the presence of modified
      carbohydrates and temperature conditions. Interestingly, it was found that the
      activation barrier for the crystal growth of the beta polymorph is not affected
      by acetylated saccharides while the one estimated for the alpha form changes
      significantly from 48.5 kJ/mol (pure API) up to 122 kJ/mol (NIF-acMAL system).
      Moreover, the relationship between the crystal growth rate and structural
      relaxation times for pure NIF and solid dispersions were analyzed. It turned out
      that there is a clear decoupling between the crystal growth rate and structural
      dynamics in both NIF-acMAL and NIF-acSUC binary mixtures. This is in line with
      recent reports indicating the decoupling phenomenon to be a universal feature of
      soft matter in the close vicinity of the glass transition temperature.

PMID- 28489945
TI  - Quantifying Liquid Transport and Patterning Using Atomic Force Microscopy.
AB  - Atomic force microscopy (AFM) provides unique insight into the nanoscale
      properties of materials. It has been challenging, however, to use AFM to study
      soft materials such as liquids or gels because of their tendency to flow in
      response to stress. We propose an AFM-based technique for quantitatively
      analyzing the transport of soft materials from an AFM probe to a surface.
      Specifically, we present a method for loading an AFM probe with a single 0.3 to
      30 pL droplet of liquid and subsequently measuring the mass of this liquid by
      observing the change in the vibrational resonance frequency of the cantilever.
      Using this approach, the mass of this liquid was detected with picogram-scale
      precision by a commercial AFM system. Additionally, sub-femtoliter droplets of
      liquid were transferred from the probe to a surface with agreement found between
      the real-time change in mass of the liquid-loaded probe and the volume of the
      feature written on the surface. To demonstrate the utility of this approach in
      studying nanoscale capillary and transport phenomena, we experimentally determine
      that the quantity of liquid transported from the tip to a surface in a given
      patterning operation scales as the mass of liquid on the probe to the 1.35 power.
      In addition to providing new avenues for studying the dynamics of soft materials
      on the nanoscale, this method can improve nanopatterning of soft materials by
      providing in situ feedback.

PMID- 28489946
TI  - Transformation of Nitrogen and Evolution of N-Containing Species during Algae
      Pyrolysis.
AB  - Transformation and evolution mechanisms of nitrogen during algae pyrolysis were
      investigated in depth with exploration of N-containing products under variant
      temperature. Results indicated nitrogen in algae is mainly in the form of protein
      N (~90%) with some inorganic-N. At 400-600  degrees C, protein-N in algae cracked
      first with algae pyrolysis and formed pyridinic-N, pyrrolic-N, and quaternary-N
      in char. The content of protein-N decreased significantly, while that of pyrrolic
      N and quaternary-N increased gradually with temperature increasing. Pyridinic-N
      and pyrrolic-N formation was due to deamination or dehydrogenation of amino
      acids; subsequently, some pyridinic-N converted to quaternary-N. Increasing
      temperature decreased amides content greatly while increased that of nitriles and
      N-heterocyclic compounds (pyridines, pyrroles, and indoles) in bio-oil. Amides
      were formed through NH3 reacting with fatty acids, that underwent dehydration to
      form nitriles. Besides, NH3 and HCN yields increased gradually. NH3 resulted from
      ammonia-N, labile amino acids and amides decomposition, while HCN came from
      nitrile decomposition. At 700-800  degrees C, evolution trend of N-containing
      products was similar to that at 400-600  degrees C. While N-heterocyclic
      compounds in bio-oil mainly came from pyrifinic-N, pyrrolic-N, and quaternary-N
      decomposition. Moreover, cracking of pyridinic-N and pyrrolic-N produced HCN and
      NH3. A mechanism of nitrogen transformation during algae pyrolysis is proposed
      based on amino acids decomposition.

PMID- 28489948
TI  - Cellulose Nanocrystals/Polyacrylamide Composites of High Sensitivity and Cycling
      Performance To Gauge Humidity.
AB  - Cellulose nanocrystals (CNCs) have attracted much interest due to their unique
      optical property, rich resource, environment friendliness, and templating
      potentials. CNCs have been reported as novel photonic humidity sensors, which are
      unfortunately limited by the dissolution and unideal moisture absorption of CNCs.
      We, in this study, developed a high-performance photonic humidity composite
      sensor that consisted of CNCs and polyacrylamide; chemical bonding was induced
      between the two components by using glutaraldehyde as a bridging agent. The
      composites inherited the chiral nematic structure of CNCs and maintained it well
      through a cycling test. A distinct color change was observed for these composites
      used as a humidity indicator; the change was caused by polyacrylamide swelling
      with water and thus enlarging the helical pitch of the chiral nematic structure.
      The composites showed no degradation of the sensing performance through cycling.
      The excellent cycling stability was attributed to the bonding between
      polyacrylamide and CNCs. This composite strategy can extend to the development of
      other photonic indicators.

PMID- 28489947
TI  - Determination of Ion Atmosphere Effects on the Nucleic Acid Electrostatic
      Potential and Ligand Association Using AH+.C Wobble Formation in Double-Stranded
      DNA.
AB  - The high charge density of nucleic acids and resulting ion atmosphere profoundly
      influence the conformational landscape of RNA and DNA and their association with
      small molecules and proteins. Electrostatic theories have been applied to
      quantitatively model the electrostatic potential surrounding nucleic acids and
      the effects of the surrounding ion atmosphere, but experimental measures of the
      potential and tests of these models have often been complicated by conformational
      changes and multisite binding equilibria, among other factors. We sought a simple
      system to further test the basic predictions from electrostatics theory and to
      measure the energetic consequences of the nucleic acid electrostatic field. We
      turned to a DNA system developed by Bevilacqua and co-workers that involves a
      proton as a ligand whose binding is accompanied by formation of an internal AH+.C
      wobble pair [Siegfried, N. A., et al. Biochemistry, 2010, 49, 3225]. Consistent
      with predictions from polyelectrolyte models, we observed logarithmic dependences
      of proton affinity versus salt concentration of -0.96 +/- 0.03 and -0.52 +/- 0.01
      with monovalent and divalent cations, respectively, and these results help
      clarify prior results that appeared to conflict with these fundamental models.
      Strikingly, quantitation of the ion atmosphere content indicates that divalent
      cations are preferentially lost over monovalent cations upon A.C protonation,
      providing experimental indication of the preferential localization of more highly
      charged cations to the inner shell of the ion atmosphere. The internal AH+.C
      wobble system further allowed us to parse energetic contributions and extract
      estimates for the electrostatic potential at the position of protonation. The
      results give a potential near the DNA surface at 20 mM Mg2+ that is much less
      substantial than at 20 mM K+ (-120 mV vs -210 mV). These values and difference
      are similar to predictions from theory, and the potential is substantially
      reduced at higher salt, also as predicted; however, even at 1 M K+ the potential
      remains substantial, counter to common assumptions. The A.C protonation module
      allows extraction of new properties of the ion atmosphere and provides an
      electrostatic meter that will allow local electrostatic potential and energetics
      to be measured within nucleic acids and their complexes with proteins.

PMID- 28489949
TI  - Electronic Coupling between Graphene and Topological Insulator Induced Anomalous
      Magnetotransport Properties.
AB  - It has been theoretically proposed that the spin textures of surface states in a
      topological insulator can be directly transferred to graphene by means of the
      proximity effect, which is very important for realizing a two-dimensional
      topological insulator based on graphene. Here we report the anomalous
      magnetotransport properties of graphene-topological insulator Bi2Se3
      heterojunctions, which are sensitive to the electronic coupling between graphene
      and the topological surface state. The coupling between the pz orbitals of
      graphene and the p orbitals of the surface states on the Bi2Se3 bottom surface
      can be enhanced by applying a perpendicular negative magnetic field, resulting in
      a giant negative magnetoresistance at the Dirac point up to about -91%. An
      obvious resistance dip in the transfer curve at the Dirac point is also observed
      in the hybrid devices, which is consistent with theoretical predictions of the
      distorted Dirac bands with nontrivial spin textures inherited from the Bi2Se3
      surface states.

PMID- 28489950
TI  - Return of D4 Dopamine Receptor Antagonists in Drug Discovery.
AB  - The dopamine D4 receptor garnered a great deal of interest in the early 1990s
      when studies showed the atypical antipsychotic clozapine possessed higher
      affinity for D4, relative to other dopamine receptor subtypes, and that this
      activity might underlie the unique clinical efficacy of clozapine. Unfortunately,
      D4 antagonists that were developed for schizophrenia failed in the clinic. Thus,
      D4 fell out of favor as a therapeutic target, and work in this area was silent
      for decades. Recently, D4 ligands with improved selectivity for D4 against not
      only D1-3,5 but also other biogenic amine targets have emerged, and D4 is once
      again in the spotlight as a novel target for both addiction and Parkinson's
      disease (PD), as well as other emerging diseases. This report will review the
      historical data for D4, review the known D4 ligands, and then highlight new data
      supporting a role for D4 inhibition in addiction, PD, and cancer.

PMID- 28489951
TI  - Direct Observation of Changes in Focal Conic Domains of Cholesteric Films Induced
      by Ultraviolet Irradiation.
AB  - The helical supramolecular structure of cholesteric liquid crystalline (LC) films
      predetermines their outstanding optical properties and the unique nanostructure
      of their surface. The introduction of photochromic dopants in these films opens
      up an interesting possibility for creation of smart cholesteric materials with
      photocontrollable optical and photovariable surface properties. Using atomic
      force microscopy (AFM), we performed in situ measurements of the surface
      topography of cyclosiloxane LC cholesteric oligomer films during the cholesteric
      helix twisting caused by their preliminary ultraviolet (UV) irradiation. A chiral
      photochromic isosorbide-based dopant was introduced in the films to control the
      cholesteric helix pitch by UV-irradiation. The initial films are characterized by
      planar texture with the presence of focal conic domains having the double-spiral
      relief on their surface. UV-irradiation of these films leads to the cholesteric
      helix twisting resulting in a decrease in the surface relief period, and the
      enlargement of defect areas between the domains. The detailed mechanisms of the
      rearrangement of the film surface structure due to the cholesteric helix twisting
      are suggested. They include the rotation and displacement of cholesteric layers
      in the bulk, and the nucleation of new ones at the surface in defect regions.

PMID- 28489952
TI  - Revisiting Hydrogen Bond Thermodynamics in Molecular Simulations.
AB  - In processes involving aqueous solutions and in almost every biomolecular
      interaction, hydrogen bonds play important roles. Though weak compared to the
      covalent bond, hydrogen bonds modify the stability and conformation of numerous
      small and large molecules and modulate their intermolecular interactions. We
      propose a simple methodology for extracting hydrogen bond strength from atomistic
      level simulations. The free energy associated with hydrogen bond formation is
      conveniently calculated as the reversible work required to reshape a completely
      random pair probability distribution reference state into the one found in
      simulations where hydrogen bonds are formed. Requiring only the probability
      density distribution of donor-acceptor pairs in the first solvation shell of an
      electronegative atom, the method uniquely defines the free energy, entropy, and
      enthalpy of the hydrogen bond. The method can be easily extended to molecules
      other than water and to multiple component mixtures. We demonstrate and apply
      this methodology to hydrogen bonds that form in molecular dynamics simulations
      between water molecules in pure water, as well as to bonds formed between
      different molecules in a binary mixture of a sugar (trehalose) and water.
      Finally, we comment on how the method should be useful in assessing the role of
      hydrogen bonds in different molecular mechanisms.

PMID- 28489953
TI  - Vascular function and arginine and dimethylarginines in gentamicin-induced renal
      failure: a possible effect of heme oxygenase 1 inducer hemin.
AB  - Increased oxidative stress and disturbance in nitric oxide bioavailability lead
      to endothelial dysfunction and cardiovascular complication in renal disease.
      Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal
      proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we
      investigated whether heme oxygenase 1 HO-1) induction influenced kidney and
      vascular function in GM-administered rats. GM (100 mg.kg-1.day-1; i.p.) was given
      to rats alone or together with hemin (20 mg.kg-1 on alternate days; i.p.) for 14
      days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and
      symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels
      and myeloperoxidase (MPO) activity were measured. Histopathological examinations
      of kidney and relaxation and contraction responses of aorta were also examined.
      GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused
      histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA
      expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme
      activities and l-arginine levels in the kidney. Decreased relaxation and
      contraction were detected in the aorta. Hemin restored renal oxidative stress and
      inflammatory changes together with vascular dysfunction, but did not affect SDMA,
      BUN, or creatinine levels. We conclude that HO-1 induction may be effective in
      improving renal oxidative stress, inflammation, and vascular dysfunction mediated
      by GM.

PMID- 28489954
TI  - Astaxanthin Prevented Oxidative Stress in Heart and Kidneys of Isoproterenol
      Administered Aged Rats.
AB  - The objective of this study was to investigate the effect of astaxanthin on
      isoproterenol (ISO)-induced myocardial infarction and cardiac hypertrophy in
      rats. To evaluate the effect of astaxanthin on ISO-induced cardiac dysfunction,
      18 aged Long Evans male rats were evenly divided into three groups. Group I
      (Control group) was given only the laboratory-ground food and normal water. Group
      II (ISO group) was administered ISO at a dose of 50 mg/kg subcutaneously (SC)
      twice a week for two weeks. Group III (Astaxanthin + ISO group) was treated with
      astaxanthin (25 mg/kg) orally every day and ISO 50 mg/kg SC twice a week for two
      weeks. ISO administration in rats increased the heart and left ventricular wet
      weights and increased inflammatory cell infiltration and fibrosis. Moreover, ISO
      administration increased the lipid peroxidation and decreased antioxidant enzyme
      activities in heart tissues. Astaxanthin treatment prevented the increased wet
      weight of heart and decreased inflammatory cell infiltration and fibrosis. The
      protective effect of astaxanthin was associated with reduction of free radicals
      by improving antioxidant enzyme function, as well as normalization and/or
      suppression of elevated oxidative stress markers, such as malondialdehyde (MDA),
      nitric oxide (NO), and advanced protein oxidation product (APOP) in ISO
      administered rats. Furthermore, astaxanthin decreased the elevated activities of
      aspartate transaminase (AST), alanine transaminase (ALT), and creatinin kinase
      muscle/brain (CK-MB) in ISO-administered rats. In conclusion, astaxanthin may
      protect cardiac tissues in ISO-administered rats through suppression of oxidative
      stress and enhancement of antioxidant enzyme functions.

PMID- 28489955
TI  - Isometric and dynamic strength and neuromuscular attributes as predictors of
      vertical jump performance in 11- to 13-year-old male athletes.
AB  - In explosive contractions, neural activation is a major factor in determining the
      rate of torque development, while the latter is an important determinant of jump
      performance. However, the contribution of neuromuscular activation and rate of
      torque development to jump performance in children and youth is unclear. The
      purpose of this study was to examine the relationships between the rate of
      neuromuscular activation, peak torque, rate of torque development, and jump
      performance in young male athletes. Forty-one 12.5 +/- 0.5-year-old male soccer
      players completed explosive, unilateral isometric and dynamic (240 degrees /s)
      knee extensions (Biodex System III), as well as countermovement-, squat-, and
      drop-jumps. Peak torque (pT), peak rate of torque development (pRTD), and rate of
      vastus lateralis activation (Q30) during the isometric and dynamic contractions
      were examined in relation to attained jump heights. Isometric pT and pRTD were
      strongly correlated (r = 0.71) but not related to jump performance. Dynamic pT
      and pRTD, normalized to body mass, were significantly related to jump height in
      all 3 jumps (r = 0.38-0.66, p < 0.05). Dynamic normalized, but not absolute pRTD,
      was significantly related to Q30 (r = 0.35, p < 0.05). In young soccer players,
      neuromuscular activation and rate of torque development in dynamic contractions
      are related to jump performance, while isometric contractions are not. These
      findings have implications in the choice of training and assessment methods for
      young athletes.

PMID- 28489956
TI  - The Role of Chlorogenic Acid Supplementation in Anemia and Mineral Disturbances
      Induced by 4-Tert-Octylphenol Toxicity.
AB  - 4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful
      effects to human health. Chlorogenic acid is the major dietary polyphenol present
      in various foods and beverages. The aim of the present study was to evaluate the
      protective role of chlorogenic acid in anemia and mineral disturbance occurring
      in OP toxicity in rats. Thirty-two male albino rats were divided into four equal
      groups (8 rats/group) as follows. The first (control) group was treated daily
      with an oral dose of 1 ml saline for two weeks. The second group was treated
      daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks.
      The third and fourth groups received daily intraperitoneal (ip) injections with
      100 mg OP/kg body weight for two weeks; the fourth group was treated daily with
      an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting
      one week before OP injections. The results revealed that OP induced significant
      decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell
      hemoglobin, mean cell hemoglobin concentration, platelet count, white blood
      cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium,
      phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione
      peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover,
      significant increases in serum hepcidin, ferritin, transferrin, erythropoietin,
      aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea,
      creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein
      carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis.
      Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned
      parameters to approach the normal values. In conclusion, chlorogenic acid
      protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by
      ameliorating oxidative stress and apoptosis.

PMID- 28489957
TI  - Unravelling pathogenetic mechanisms of epidemic lineages.

PMID- 28489958
TI  - Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by
      inhibiting bacterial invasion of central nervous systems.
AB  - Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we
      investigated whether pneumococcal paralogous zinc metalloproteases contribute to
      meningitis onset. Findings of codon-based phylogenetic analyses indicated 3 major
      clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD as a subgroup. In
      vitro invasion assays of human brain microvascular endothelial cells (hBMECs)
      showed that deletion of the zmpC gene in S. pneumoniae strain TIGR4 significantly
      increased bacterial invasion into hBMECs, whereas deletion of either zmpA or zmpB
      had no effect. In a mouse meningitis model, the zmpC deletion mutant exhibited
      increased invasion of the brain and was associated with increased matrix
      metalloproteinase-9 in plasma and mortality as compared with the wild type. We
      concluded that ZmpC suppresses pneumococcal virulence by inhibiting bacterial
      invasion of the central nervous system. Furthermore, ZmpC illustrates the
      evolutional theory stating that gene duplication leads to acquisition of novel
      function to suppress excessive mortality.

PMID- 28489959
TI  - Mood disorders in adult asthma phenotypes.
AB  - OBJECTIVE: Studies show high comorbidity of mood disorders in asthma. As asthma
      is a highly heterogeneous disease with different phenotypes it can be expected
      that there is a difference in this association with different asthma phenotypes.
      The aim of our cross-sectional study was to assess the association of specific
      asthma phenotypes with anxiety and/or depression and their impact on asthma
      control. METHODS: A cross-sectional study in 201 consecutive adult outpatients
      with asthma (>=18 years of age) was conducted. Each patient underwent physical
      examination, detailed medical history, Hospital Anxiety and Depression Scale,
      Asthma Control Questionnaire, Asthma Control Test, together with measurements of
      lung function and fraction of exhaled nitric oxide. Phenotypes were assessed
      using cluster analysis, and a multivariate analysis was used to identify
      associations of mood disorders with different phenotypes. RESULTS: Five asthma
      phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory
      disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%),
      and respiratory infections associated asthma (RIAA, 5.5%). A multivariate
      analysis showed a significant association of anxiety with LOA and comorbid
      hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012),
      and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA,
      OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid
      anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score
      (AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ,
      OR = 1.90; p < 0.001. CONCLUSION: Mood disorders were significantly associated
      with AA, LOA, and infection-associated asthma, together with comorbid
      hypertension and the level of asthma control.

PMID- 28489960
TI  - SWAP70 is a universal GEF-like adaptor for tethering actin to phagosomes.
AB  - We recently identified a key role for SWAP70 as the tethering factor stabilizing
      F-actin filaments on the surface of phagosomes in human dendritic cells by
      interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)
      bisphosphate. In this study, we aimed to investigate whether this role of SWAP70
      was general among immune phagocytes. Our data reveal that SWAP70 is recruited to
      early phagosomes of macrophages and dendritic cells from both human and mouse.
      The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin
      polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated
      previously with knock-down. Moreover, SWAP70 was recently shown to sequester the
      F-actin severing protein cofilin and we investigated this relationship in
      phagocytosis. Our data show an increased activation of cellular cofilin upon
      siRNA knockdown of SWAP70. Finally, we explored whether SWAP70 would be recruited
      to the immune synapse between dendritic cells and T cells required for antigen
      presentation, as the formation of such synapses depends on F-actin. However, we
      observed that SWAP70 was depleted at immune synapses and specifically was
      recruited to phagosomes. Our data support an essential and specific role for
      SWAP70 in tethering and stabilizing F-actin to the phagosomal surface in a wide
      range of phagocytes.

PMID- 28489961
TI  - The role of Exo70 in exocytosis and beyond.
AB  - The exocyst complex mediates the tethering of secretory vesicles to the plasma
      membrane before SNARE-mediated membrane fusion. Recent studies have implicated
      the exocyst in a wide range of cellular processes. Particularly, research on the
      Exo70 subunit of the complex has linked the function of the exocyst in exocytosis
      to cell adhesion, migration and invasion. In this review, we will discuss the
      recent work on how Exo70 regulates these cellular processes, and how small
      GTPases and kinases interact with Exo70 to orchestrate its function in exocytosis
      and cytoskeleton organization. The study of Exo70 contributes to the
      understanding of many pathophysiological processes from organogenesis to cancer
      metastasis.

PMID- 28489962
TI  - Development and validation of a screening procedure to identify speech-language
      delay in toddlers with cleft palate.
AB  - The purpose of this study was to develop and validate a clinically useful speech
      language screening procedure for young children with cleft palate +/- cleft lip
      (CP) to identify those in need of speech-language intervention. Twenty-two
      children with CP were assigned to a +/- need for intervention conditions based on
      assessment of consonant inventory using a real-time listening procedure in
      combination with parent-reported expressive vocabulary. These measures allowed
      evaluation of early speech-language skills found to correlate significantly with
      later speech-language performance in longitudinal studies of children with CP.
      The external validity of this screening procedure was evaluated by comparing the
      +/- need for intervention assignment determined by the screening procedure to
      experienced speech-language pathologist (SLP)s' clinical judgement of whether or
      not a child needed early intervention. The results of real-time listening
      assessment showed good-excellent inter-rater agreement on different consonant
      inventory measures. Furthermore, there was almost perfect agreement between the
      children selected for intervention with the screening procedure and the clinical
      judgement of experienced SLPs indicate that the screening procedure is a valid
      way of identifying children with CP who need early intervention.

PMID- 28489964
TI  - Specific activation of PLEKHG2-induced serum response element-dependent gene
      transcription by four-and-a-half LIM domains (FHL) 1, but not FHL2 or FHL3.
AB  - PLEKHG2 is a Gbetagamma- and Galphas-dependent guanine nucleotide exchange factor
      for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways
      such as those for actin cytoskeletal reorganization and serum response element
      (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM
      domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the
      other FHL family members and found that the FHL1A specifically regulate the
      PLEKHG2 activity. Moreover, FHL1A further enhanced Gbetagamma- and PLEKHG2
      induced SRE-dependent gene transcription, whereas FHL1A partially restored the
      attenuated PLEKHG2-induced SRE-dependent gene transcription by Galphas. Our
      results suggest that FHL1A specifically interacts with PLEKHG2 to regulate a
      function of PLEKHG2 that is modified by the interaction of Gbetagamma and
      Galphas.

PMID- 28489963
TI  - The Aspergillus fumigatus farnesyltransferase beta-subunit, RamA, mediates
      growth, virulence, and antifungal susceptibility.
AB  - Post-translational prenylation mechanisms, including farnesylation and
      geranylgeranylation, mediate both subcellular localization and protein-protein
      interaction in eukaryotes. The prenyltransferase complex is an alphabeta
      heterodimer in which the essential alpha-subunit is common to both the
      farnesyltransferase and the geranylgeranyltransferase type-I enzymes. The beta
      subunit is unique to each enzyme. Farnesyltransferase activity is an important
      mediator of protein localization and subsequent signaling for multiple proteins,
      including Ras GTPases. Here, we examined the importance of protein farnesylation
      in the opportunistic fungal pathogen Aspergillus fumigatus through generation of
      a mutant lacking the farnesyltransferase beta-subunit, ramA. Although
      farnesyltransferase activity was found to be non-essential in A. fumigatus,
      diminished hyphal outgrowth, delayed polarization kinetics, decreased conidial
      viability, and irregular distribution of nuclei during polarized growth were
      noted upon ramA deletion (DeltaramA). Although predicted to be a target of the
      farnesyltransferase enzyme complex, we found that localization of the major A.
      fumigatus Ras GTPase protein, RasA, was only partially regulated by
      farnesyltransferase activity. Furthermore, the farnesyltransferase-deficient
      mutant exhibited attenuated virulence in a murine model of invasive
      aspergillosis, characterized by decreased tissue invasion and development of
      large, swollen hyphae in vivo. However, loss of ramA also led to a Cyp51A/B
      independent increase in resistance to triazole antifungal drugs. Our findings
      indicate that protein farnesylation underpins multiple cellular processes in A.
      fumigatus, likely due to the large body of proteins affected by ramA deletion.

PMID- 28489965
TI  - Evidence for the subsynaptic zone as a preferential site for CHRN recycling at
      neuromuscular junctions.
AB  - Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine
      receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper
      abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work
      showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging
      of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for
      differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis.
      Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large
      stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed
      CHRN almost exclusively at neuromuscular junctions. In agreement with previous
      findings, this data suggests the existence of a specialized subsynaptic zone that
      is particularly relevant for CHRN recycling.

PMID- 28489966
TI  - Acrylamide-induced disturbance of the redox balance in the chick embryonic brain.
AB  - This study was undertaken to determine the redox balance in the developing brain
      after exposure to acrylamide (ACR), a potent neurotoxin. The studies were
      performed using an in ovo chick embryo model. The antioxidant enzymes SOD, GPx,
      CAT, and reduced glutathione (GSH) were used as indicators of the redox balance.
      Eggs were injected with ACR doses of 40 mg kg-1 egg mass (2.4 mg egg-1) on
      embryonic day 17 (E17). The activity of the antioxidant enzymes and the
      concentration of GSH were measured at E17, E18, and E19 in the medulla oblongata,
      cerebrum, cerebellum, and optic lobe. The results indicated a significant
      decrease in the GSH concentrations in the optic lobe (E19, E20) and cerebrum
      (E20) of embryos exposed to ACR. The activities of SOD and GPx were significantly
      increased in the majority of the examined structures after injection of ACR. CAT
      activity was completely inhibited in the brains of the embryos exposed to ACR
      compared to that in the brains of the control embryos. Thus, we concluded that
      ACR exerts a significant influence on the redox balance in the developing brain
      by impacting the activity of antioxidant enzymes and the levels of GSH.

PMID- 28489968
TI  - Tailoring Multicomponent Writing Interventions: Effects of Coupling Self
      Regulation and Transcription Training.
AB  - Writing proficiency is heavily based on acquisition and development of self
      regulation and transcription skills. The present study examined the effects of
      combining transcription training with a self-regulation intervention (self
      regulated strategy development [SRSD]) in Grade 2 (ages 7-8). Forty-three
      students receiving self-regulation plus transcription (SRSD+TR) intervention were
      compared with 37 students receiving a self-regulation only (SRSD only)
      intervention and 39 students receiving the standard language arts curriculum.
      Compared with control instruction, SRSD instruction-with or without transcription
      training-resulted in more complex plans; longer, better, and more complete
      stories; and the effects transferred to story written recall. Transcription
      training produced an incremental effect on students' composing skills. In
      particular, the SRSD+TR intervention increased handwriting fluency, spelling
      accuracy for inconsistent words, planning and story completeness, writing
      fluency, clause length, and burst length. Compared with the SRSD-only
      intervention, the SRSD+TR intervention was particularly effective in raising the
      writing quality of poorer writers. This pattern of findings suggests that
      students benefit from writing instruction coupling self-regulation and
      transcription training from very early on. This seems to be a promising
      instructional approach not only to ameliorate all students' writing ability and
      prevent future writing problems but also to minimize struggling writers'
      difficulties and support them in mastering writing.

PMID- 28489967
TI  - Associations of the Polymorphisms in DHRS4, SERPING1, and APOR Genes with
      Postmortem pH in Berkshire Pigs.
AB  - Postmortem pH is a main factor influencing the meat quality in pigs. This study
      investigated the association of postmortem pH with single-nucleotide
      polymorphisms (SNPs) in the fourth member of the short-chain
      dehydrogenase/reductase family (DHRS4), the first member of serpin peptidase
      inhibitor, clade G (complement inhibitor) (SERPING1), and the apolipoprotein R
      precursor (APOR) genes in Berkshire pigs. The study included 437 pigs, and
      genotyping was conducted using the GoldenGate Assay (Illumina, San Diego, CA,
      USA). DHRS4, SERPING1, and APOR polymorphisms were significantly associated with
      pH45 or pH24 (p < 0.05). SERPING1 was also statistically significantly associated
      with water holding capacity (p < 0.05), which is closely associated with
      postmortem pH. These results suggest that SNPs in the DHRS4, SERPING1, and APOR
      genes have potential for use as genetic markers for the meat quality in pigs.

PMID- 28489969
TI  - Barriers toward help-seeking among young men prior to suicide.
AB  - This study explores barriers to help-seeking among young men prior to suicide. We
      analyzed 61 in-depth interviews with parents, siblings, friends, and ex-partners
      of 10 young men (aged 18-30) with no record of mental illness, as well as 6
      suicide notes, using interpretative phenomenological analysis. Three barriers
      emerged: (a) a total defeat; (b) no room for weakness; and (c) fear of mental
      disorder. The shame from falling short of standards (own/significant male
      others') could be a considerable barrier to help-seeking in a suicidal crisis.

PMID- 28489970
TI  - Photostability study of cis-configuration neonicotinoid insecticide cycloxaprid
      in water.
AB  - Cycloxaprid (CYC) is a new cis-configuration neonicotinoid insecticide, which is
      currently under development in China for agricultural pest control. Considering
      the photodegradation of CYC is important for the application of CYC in the
      future, the photochemical behavior of CYC in aqueous solution was herein
      investigated in a "merry-go-round" reactor under a 300 W high-pressure mercury
      lamp. Twenty-five photodegradation products were identified via UPLC-TOF-ESI
      MS/MS. The results suggested that NTN32692, the precursor of CYC was the
      predominant photodegradation product. CYC photodegrades via a more complex
      mechanism than imidacloprid and four potential photodegradation pathways were
      proposed.

PMID- 28489971
TI  - Phylogenetic systematics of Syncephalis (Zoopagales, Zoopagomycotina), a genus of
      ubiquitous mycoparasites.
AB  - We examined phylogenetic relationships among species of the mycoparasite genus
      Syncephalis using sequences from three nuclear ribsosomal DNA genes (18S, 5.8S,
      and 28S nuc rDNA) and a gene encoding the largest subunit of RNA polymerase II
      (RPB1). Our data set included 88 Syncephalis isolates comprising 23 named species
      and several unnamed taxa. We also revived a culturing technique using beef liver
      and cellophane to grow several Syncephalis isolates without their host fungi to
      obtain pure parasite DNA. Most isolates, however, were grown in co-cultures with
      their host fungi, so we designed Syncephalis-specific primers to obtain sequence
      data. Individual and combined data sets were analyzed by maximum likelihood (ML)
      and Bayesian methods. We recovered 20 well-supported lineages and 38 operational
      taxonomic units (OTUs). Most major clades contained isolates from distant
      localities on multiple continents. There were taxonomic and nomenclature issues
      within several clades, probably due to high phenotypic plasticity or species
      dimorphism. We also conducted an analysis of Syncephalis nuc rDNA internal
      transcribed spacer (ITS) sequences for 31 phylogenetically diverse isolates, and
      we determined that most Syncephalis species have long ITS sequences relative to
      other fungi. Although commonly employed eukaryotic and fungal primers are
      compatible with diverse Syncephalis species, the ITS sequences of Syncepahlis are
      nonetheless rarely recovered in environmental molecular diversity surveys.

PMID- 28489972
TI  - Continuous bioelectricity generation through treatment of Victoria blue R: A
      novel microbial fuel cell operation.
AB  - A novel two-chamber microbial fuel cell (MFC) operation with a continuous
      anaerobic-aerobic decolorization system was developed to improve the degradation
      of the triphenylmethane dye, Victoria blue R (VBR). In addition, bioelectricity
      was generated during the VBR degradation process, and the operation parameters
      were optimized. The results indicated that the VBR removal efficiency and
      electricity generation were affected by the VBR concentration, liquid retention
      time (LRT), external resistance, gas retention time (GRT), and shock loading. The
      optimal operation parameters were as follows: VBR concentration, 600 mg L-1; LRT,
      24 h; external resistance, 3300 Omega; and GRT, 60 s. Under these operating
      conditions, the VBR removal efficiency, COD removal efficiency, and power density
      were 98.2% +/- 0.3%, 97.6% +/- 0.5%, and 30.6 +/- 0.4 mW m-2, respectively.
      According to our review of the relevant literature, this is the first paper to
      analyze the electrical characteristics of a continuous two-chamber MFC operation
      and demonstrate the feasibility of the simultaneous electricity generation and
      decolorization of VBR.

PMID- 28489973
TI  - Selected aspects of the current state of freshwater resources in the Murmansk
      region, Russia.
AB  - Aspects of reducing the resource potential of surface waters of the Murmansk
      region in the global climate change and the environment and their irrational use
      have been considered. Increase of aquatic environment toxicity, drastic
      restructuring of the structural and functional characteristics of aquatic
      communities, changes in trophic status of lakes, reducing the stability of
      freshwater ecosystems, increasing the risk of catastrophic degradation have been
      shown. Taking into account the regional peculiarities, some indicators of surface
      water quality in the Murmansk region have been proposed.

PMID- 28489974
TI  - Diversity of the TLR4 Immunity Receptor in Czech Native Cattle Breeds Revealed
      Using the Pacific Biosciences Sequencing Platform.
AB  - The allelic variants of immunity genes in historical breeds likely reflect local
      infection pressure and therefore represent a reservoir for breeding. Screening to
      determine the diversity of the Toll-like receptor gene TLR4 was conducted in two
      conserved cattle breeds: Czech Red and Czech Red Pied. High-throughput sequencing
      of pooled PCR amplicons using the PacBio platform revealed polymorphisms, which
      were subsequently confirmed via genotyping techniques. Eight SNPs found in coding
      and adjacent regions were grouped into 18 haplotypes, representing a significant
      portion of the known diversity in the global breed panel and presumably exceeding
      diversity in production populations. Notably, the ancient Czech Red breed
      appeared to possess greater haplotype diversity than the Czech Red Pied breed, a
      Simmental variant, although the haplotype frequencies might have been distorted
      by significant crossbreeding and bottlenecks in the history of Czech Red cattle.
      The differences in haplotype frequencies validated the phenotypic distinctness of
      the local breeds. Due to the availability of Czech Red Pied production herds, the
      effect of intensive breeding on TLR diversity can be evaluated in this model. The
      advantages of the Pacific Biosciences technology for the resequencing of long PCR
      fragments with subsequent direct phasing were independently validated.

PMID- 28489975
TI  - Biodegradation of airborne acetone/styrene mixtures in a bubble column reactor.
AB  - The ability of a bubble column reactor (BCR) to biodegrade a mixture of styrene
      and acetone vapors was evaluated to determine the factors limiting the process
      efficiency, with a particular emphasis on the presence of degradation
      intermediates and oxygen levels. The results obtained under varied loadings and
      ratios were matched with the dissolved oxygen levels and kinetics of oxygen mass
      transfer, which was assessed by determination of kLa coefficients. A 1.5-L
      laboratory-scale BCR was operated under a constant air flow of 1.0 L.min-1, using
      a defined mixed microbial population as a biocatalyst. Maximum values of
      elimination capacities/maximum overall specific degradation rates of 75.5 gC.m
      3.h-1/0.197 gC.gdw-1.h-1, 66.0 gC.m-3.h-1/0.059 gC.gdw-1.h-1, and 45.8 gC.m-3.h
      1/0.027 gC.gdw-1.h-1 were observed for styrene/acetone 2:1, styrene-rich and
      acetone-rich mixtures, respectively, indicating significant substrate
      interactions and rate limitation by biological factors. The BCR removed both
      acetone and styrene near-quantitatively up to a relatively high organic load of
      50 g.m-3.h-1. From this point, the removal efficiencies declined under increasing
      loading rates, accompanied by a significant drop in the dissolved oxygen
      concentration, showing a process transition to oxygen-limited conditions.
      However, the relatively efficient pollutant removal from air continued, due to
      significant oxygen mass transfer, up to a threshold loading rate when the
      accumulation of acetone and degradation intermediates in the aqueous medium
      became significant. These observations demonstrate that oxygen availability is
      the limiting factor for efficient pollutant degradation and that accumulation of
      intermediates may serve as an indicator of oxygen limitation. Microbial
      (activated sludge) analyses revealed the presence of amoebae and active nematodes
      that were not affected by variations in operational conditions.

PMID- 28489976
TI  - Testing the efficiency of extraction of incurred residues from soil with
      optimized multi-residue method.
AB  - The reproducibility of extraction of residues from spiked soil samples and from
      soils containing incurred residues was tested with 14C-labeled test compounds of
      different physical-chemical properties. Nearly 100% of the compounds added to the
      sample before extraction could be recovered with an average reproducibility
      relative standard deviation (CV) of 5.4%. The additional steps of the
      determination process (cleanup, evaporation, etc.) contributed to the major part
      of the variability of the results (CV = 10-20%). The incurred residues were most
      efficiently extracted with acetone for 30 min followed by the mixture of
      acetone/ethyl acetate 1:1 for additional 30 min. However, they could only be
      recovered at various extent (64-90% of total residues), underlying the importance
      of testing the efficiency of extraction. The residues were identified and
      quantified by gas chromatography applying thermionic detector. The performance
      parameters of the method complied with the international method validation
      guidelines, and they proved to be robust and suitable for determination of
      pesticide residues in soils of widely different physical-chemical properties.

PMID- 28489977
TI  - Distribution of pesticide residues in soil and uncertainty of sampling.
AB  - Pesticide residues were determined in about 120 soil cores taken randomly from
      the top 15 cm layer of two sunflower fields about 30 days after preemergence
      herbicide treatments. Samples were extracted with acetone-ethyl acetate mixture
      and the residues were determined with GC-TSD. Residues of dimethenamid,
      pendimethalin, and prometryn ranged from 0.005 to 2.97 mg/kg. Their relative
      standard deviations (CV) were between 0.66 and 1.13. The relative frequency
      distributions of residues in soil cores were very similar to those observed in
      root and tuber vegetables grown in pesticide treated soils. Based on all
      available information, a typical CV of 1.00 was estimated for pesticide residues
      in primary soil samples (soil cores). The corresponding expectable relative
      uncertainty of sampling is 20% when composite samples of size 25 are taken. To
      obtain a reliable estimate of the average residues in the top 15 cm layer of soil
      of a field up to 8 independent replicate random samples should be taken. To
      obtain better estimate of the actual residue level of the sampled filed would be
      marginal if larger number of samples were taken.

PMID- 28489978
TI  - Sodium bisulfate and a sodium bisulfate/tannin mixture decreases pH when added to
      an in vitro incubated poultry cecal or fecal contents while reducing Salmonella
      Typhimurium marker strain survival and altering the microbiome.
AB  - The objective of the present study was to investigate the ability of animal feed
      grade sodium bisulfate (SBS) and a mixture of sodium bisulfate/tannin to inhibit
      the growth of Salmonella using an anerobic in vitro mixed cecal culture to mimic
      the conditions within the chicken cecum. An initial inoculum of Salmonella
      Typhimurium was introduced to an anerobic dilution solution containing 1/3000
      diluted cecal bacteria and solids consisting of ground chicken feed and different
      percentages of solid SBS or SBS/tannin, and surviving organisms were enumerated.
      Two different experimental designs were employed. In the "unadapted" treatment,
      the S. Typhimurium was added at the beginning of the culture incubation along
      with cecal bacteria and chicken feed/SBS or chicken feed/SBS/tannin. In the
      "adapted" treatment, S. Typhimurium was added after a 24 hour pre-incubation of
      the cecal bacteria with the chicken feed/SBS or chicken feed/SBS/tannin. Adding
      SBS resulted in reduction of pH in the cultures which paralleled with the
      reduction of S. Typhimurium. The SBS alone was found to be inhibitory to S.
      Typhimurium in the adapted treatment at all concentrations tested (0.25, 0.5, and
      0.75%), and the degree of inhibition was concentration-dependent. Salmonella
      Typhimurium was completely killed in the adapted culture with 0.5% SBS after 24
      and 48 h. The SBS/tannin mixture was less inhibitory than SBS alone at the same
      concentrations in side-by-side comparisons. Testing at a 0.5% SBS concentration,
      chicken age had little or no effect on log reduction of S. Typhimurium relative
      to age-matched control cultures without SBS, but age did affect the absolute
      number of S. Typhimurium surviving, with the greatest decreases occurring at 2
      and 4 weeks of age (approx. 103 S. Typhimurium surviving) compared to 6 weeks of
      age (approx. 105 Salmonella surviving). Microbiome analysis with an Illumina
      MiSeq platform was conducted to investigate bacterial compositional changes
      related to the addition of SBS. The relative abundance of Firmicutes (at the
      phylum level) was decreased, and genera Lactobacillus and Faecalibacterium were
      increased when SBS was added to the anaerobic mixed culture containing either
      fecal or cecal material. The antimicrobial action of feed-grade SBS may represent
      a potential pre-harvest control measure for Salmonella in poultry production.

PMID- 28489979
TI  - Bending the Curve of Advanced Urothelial Carcinoma.

PMID- 28489980
TI  - Practical Approach to Triple-Negative Breast Cancer.
AB  - Triple negative is a term applied to breast cancers that do not meaningfully
      express the estrogen or progesterone hormone receptors or overexpress the human
      epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven
      method for systemic management of triple-negative breast cancer for both early
      stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a
      comprehensive review of management strategies that are best supported by
      available data. We also review recent advances most likely to affect treatment of
      triple-negative breast cancer in the coming years with particular emphasis on
      targeted agents, biologics, and immunotherapy.

PMID- 28489981
TI  - Evolving Treatment of Advanced Urothelial Cancer.
AB  - Urothelial cancer of the bladder is a smoking-related cancer and the fifth most
      common cancer in the United States. At presentation, up to 25% of patients will
      have muscle-invasive disease and, despite cystectomy or bladder-sparing
      trimodality approaches, will develop metastatic disease. Cisplatin-based
      combination chemotherapy regimens remain the standard of care in first-line
      metastatic disease. Although response rates to these regimens are high, they are
      rarely durable, and median overall survival is only 12 to 15 months. Treatment
      options following progression on cisplatin-based regimens or for patients unfit
      for cisplatin due to poor performance status, impaired renal function, or
      comorbidities have been quite limited. However, there is now a new class of drugs
      known as immune checkpoint inhibitors, which target the programmed cell death
      1/programmed cell death-ligand 1 axis and promote antitumor immunity, that are
      showing both efficacy and tolerability. These drugs have now been approved for
      use in both cisplatin-treated and most recently cisplatin-unfit patients.
      Clinical trials are currently ongoing to determine how best to use these drugs
      and whether they should be used alone or in combination with other treatments.
      This review will discuss the current standard of care in the management of
      urothelial cancer and highlight recent trials of immunotherapy in this disease.

PMID- 28489982
TI  - Triple-Negative Breast Cancer: Current Practice and Future Directions.

PMID- 28489983
TI  - Outstanding Questions in the Clinical Management of Triple-Negative Breast
      Cancer.

PMID- 28489984
TI  - No Bridge Over Troubled Water: Slow Progress in Bladder Cancer.

PMID- 28489986
TI  - Live to 70 Years and Older or Suffer in Silence: Understanding Health Insurance
      Status Among the Elderly Under the NHIS in Ghana.
AB  - Ghana has introduced a National Health Insurance Scheme (NHIS). Embedded in the
      NHIS is a policy to exempt poor and vulnerable groups from premiums and user
      fees. There has been some debate as to why the start-off age for exemption among
      the elderly is 70 years. Ghana has a shorter life expectancy than middle- and
      high-income countries and its current age of retirement is 60 years. This study
      explores the financial and social implications of continuing to charge premiums
      to people aged 60 to 69 years. Based on the analysis of data from a
      representative household survey, it is recommended that the exemption policy
      should be expanded to include all vulnerable elderly persons, regardless of age.

PMID- 28489985
TI  - Preclinical evaluation of the imipridone family, analogs of clinical stage anti
      cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212.
AB  - Anti-cancer small molecule ONC201 upregulates the integrated stress response
      (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene
      activation. ONC201 is under investigation in multiple clinical trials to treat
      patients with cancer. Given the unique imipridone core chemical structure of
      ONC201, we synthesized a series of analogs to identify additional compounds with
      distinct therapeutic properties. Several imipridones with a broad range of in
      vitro potencies were identified in an exploration of chemical derivatives. Based
      on in vitro potency in human cancer cell lines and lack of toxicity to normal
      human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further
      study. Both analogs inhibited colony formation, and induced apoptosis and
      downstream signaling that involves the integrated stress response and Akt/ERK,
      similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of
      cell migration while ONC212 exhibited rapid kinetics of activity. ONC212 was
      further tested in >1000 human cancer cell lines in vitro and evaluated for safety
      and anti-tumor efficacy in vivo. ONC212 exhibited broad-spectrum efficacy at
      nanomolar concentrations across solid tumors and hematological malignancies. Skin
      cancer emerged as a tumor type with improved efficacy relative to ONC201. Orally
      administered ONC212 displayed potent anti-tumor effects in vivo, a broad
      therapeutic window and a favorable PK profile. ONC212 was efficacious in vivo in
      BRAF V600E melanoma models that are less sensitive to ONC201. Based on these
      findings, ONC212 warrants further development as a drug candidate. It is clear
      that therapeutic utility extends beyond ONC201 to include additional imipridones.

PMID- 28489987
TI  - Bioengineering of an Intraabdominal Endocrine Pancreas.

PMID- 28489988
TI  - CABG at 50 (or 107?) - The Complex Course of Therapeutic Innovation.

PMID- 28489989
TI  - Left Ventricular Assist Devices for Advanced Heart Failure.

PMID- 28489990
TI  - Left Ventricular Assist Devices for Advanced Heart Failure.

PMID- 28489991
TI  - Case 14-2017 - A 20-Year-Old Man with Pain and Swelling of the Left Calf and a
      Purpuric Rash

PMID- 28489992
TI  - Arteriovenous Malformations of the Brain.

PMID- 28489993
TI  - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PMID- 28489994
TI  - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PMID- 28489995
TI  - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PMID- 28489997
TI  - New Lessons about Endometriosis - Somatic Mutations and Disease Heterogeneity.

PMID- 28489998
TI  - Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use.

PMID- 28489996
TI  - Cancer-Associated Mutations in Endometriosis without Cancer.
AB  - BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma
      and epithelium, affects approximately 10% of reproductive-age women and can cause
      pelvic pain and infertility. Endometriotic lesions are considered to be benign
      inflammatory lesions but have cancerlike features such as local invasion and
      resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic
      lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer
      driver targeted sequencing (3 patients). Mutations were validated with the use of
      digital genomic methods in microdissected epithelium and stroma. Epithelial and
      stromal components of lesions from an additional 12 patients were analyzed by
      means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent
      activating KRAS mutations. RESULTS: Exome sequencing revealed somatic mutations
      in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations
      in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing
      System or immunohistochemical analysis. The likelihood of driver genes being
      affected at this rate in the absence of selection was estimated at P=0.001
      (binomial test). Targeted sequencing and a droplet digital PCR assay identified
      KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with
      mutations in the epithelium but not the stroma. One patient harbored two
      different KRAS mutations, c.35G->T and c.35G->C, and another carried identical
      KRAS c.35G->A mutations in three distinct lesions. CONCLUSIONS: We found that
      lesions in deep infiltrating endometriosis, which are associated with virtually
      no risk of malignant transformation, harbor somatic cancer driver mutations. Ten
      of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested
      somatic mutations appeared to be confined to the epithelial compartment of
      endometriotic lesions.

PMID- 28489999
TI  - Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use.

PMID- 28490000
TI  - Case 3-2017: A Man with Cardiac Sarcoidosis and New Diplopia and Weakness.

PMID- 28490001
TI  - Zika Virus Vaccines - A Full Field and Looking for the Closers.

PMID- 28490002
TI  - Survival and Neurodevelopment of Periviable Infants.

PMID- 28490003
TI  - Binaural Tympanic-Membrane Perforations after Blast Injury.

PMID- 28490004
TI  - Melanoma of the Foot.

PMID- 28490005
TI  - Opposing Effects of Valproic Acid Treatment Mediated by Histone Deacetylase
      Inhibitor Activity in Four Transgenic X. laevis Models of Retinitis Pigmentosa.
AB  - Retinitis pigmentosa (RP) is an inherited retinal degeneration (RD) that leads to
      blindness for which no treatment is available. RP is frequently caused by
      mutations in Rhodopsin; in some animal models, RD is exacerbated by light.
      Valproic acid (VPA) is a proposed treatment for RP and other neurodegenerative
      disorders, with a phase II trial for RP under way. However, the therapeutic
      mechanism is unclear, with minimal research supporting its use in RP. We
      investigated the effects of VPA on Xenopus laevis models of RP expressing human
      P23H, T17M, T4K, and Q344ter rhodopsins, which are associated with RP in humans.
      VPA ameliorated RD associated with P23H rhodopsin and promoted clearing of mutant
      rhodopsin from photoreceptors. The effect was equal to that of dark rearing, with
      no additive effect observed. Rescue of visual function was confirmed by
      electroretinography. In contrast, VPA exacerbated RD caused by T17M rhodopsin in
      light, but had no effect in darkness. Effects in T4K and Q344ter rhodopsin models
      were also negative. These effects of VPA were paralleled by treatment with three
      additional histone deacetylase (HDAC) inhibitors, but not other antipsychotics,
      chemical chaperones, or VPA structural analogues. In WT retinas, VPA treatment
      increased histone H3 acetylation. In addition, electron microscopy showed
      increased autophagosomes in rod inner segments with HDAC inhibitor (HDACi)
      treatment, potentially linking the therapeutic effects in P23H rhodopsin animals
      and negative effects in other models with autophagy. Our results suggest that the
      success or failure of VPA treatment is dependent on genotype and that HDACi
      treatment is contraindicated for some RP cases.SIGNIFICANCE STATEMENT Retinitis
      pigmentosa (RP) is an inherited, degenerative retinal disease that leads to
      blindness for which no therapy is available. We determined that valproic acid
      (VPA), currently undergoing a phase II trial for RP, has both beneficial and
      detrimental effects in animal models of RP depending on the underlying disease
      mechanism and that both effects are due to histone deacetylase (HDAC) inhibition
      possibly linked to autophagy regulation. Off-label use of VPA and other HDAC
      inhibitors for the treatment of RP should be limited to the research setting
      until this effect is understood and can be predicted. Our study suggests that,
      unless genotype is accounted for, clinical trials for RP treatments may give
      negative results due to multiple disease mechanisms with differential responses
      to therapeutic interventions.

PMID- 28490006
TI  - Adenoid Cystic Carcinoma of the Larynx Presenting as a Thyroid Mass and Brief
      Literature Review.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) of the larynx and trachea is very
      rare. CASE: A 45-year-old man with ACC of the larynx presenting as a thyroid mass
      is reported in this study. Physical examination revealed a large solid thyroid
      nodule in the left lobe without any lymphadenopathy. A technetium thyroid scan
      showed multinodular goiter with cold nodules in the left lobe, isthmus, and
      functioning nodules in the right lobe. A large thyroid mass originating from the
      left side of the larynx, mostly the left vocal cord and the infraglottic part,
      was seen using enhanced magnetic resonance imaging after rupture of the thyroid
      cartilage on the left side. Ultrasound-guided fine needle aspiration smears and
      cell blocks of the thyroid nodule showed highly cellular smears composed of large
      tissue fragments, three-dimensional clusters, and sheets of neoplastic cells with
      slightly enlarged round and hyperchromatic nuclei. Immunohistochemical study
      showed that the cell block expressed C-kit and CK 7 on the cribriform growth
      pattern of the tumoral cells. However, protein expression of thyroglobulin and
      thyroid transcription factor-1 was not detectable. CONCLUSION: To approach a
      thyroid nodule, direct invasion or metastatic tumors of other organs must be
      borne in mind.

PMID- 28490007
TI  - Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case
      Report.
AB  - Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary
      tract which has a low incidence rate and nonspecific symptoms. It is difficult to
      diagnose early, and the misdiagnosis rate is high. CT, MRI, upper
      gastrointestinal endoscopy, and other advanced imaging modalities should be
      combined to make a comprehensive evaluation. The diagnostic confirmation of this
      tumor type mainly depends on the pathological examination. The combination of
      surgery with other treatment modalities is effective. A review of reports on
      duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990.
      However, there are few reports on neoadjuvant chemotherapy for the disease. In
      this report, preoperative S-1 in combination with oxaliplatin neoadjuvant
      chemotherapy achieved a complete pathological response in the treatment of
      duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical
      efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to
      be further verified.

PMID- 28490008
TI  - An Uncommon ST1224 NDM-1-Producing Klebsiella pneumoniae Isolated from the
      Bloodstream of a Leukemia Patient in China.
AB  - AIMS: This study aimed to analyze the clinical data and characteristics of an NDM
      1 (New Delhi metallo-beta-lactamase-1)-producing Klebsiella pneumoniae isolated
      from the bloodstream of a leukemia patient. MATERIALS AND METHODS: A
      retrospective analysis was used for the clinical data of the patient. The
      modified Hodge test (MHT) and ethylenediaminetetraacetic acid (EDTA)-disk synergy
      test were used for detecting metallo-beta-lactamase. Antibiotic resistance was
      determined using the agar dilution method. PCR was used to identify resistance
      genes. S1-PFGE (S1 nuclease/pulsed-field gel electrophoresis) and Southern blot
      hybridization were performed to determine the location of blaNDM-1. A conjugation
      experiment was used to confirm the transferable characteristics of the resistant
      genes. Multilocus sequence typing (MLST) was also performed. RESULTS: The patient
      developed bloodstream infections caused by this NDM-1-producing strain and died
      due to worsening of the condition. The strain was highly resistant to beta-lactam
      antibiotics and coharbored blaNDM-1, qnrB, and blaCTX-M-9 genes. Southern blot
      confirmed that blaNDM-1 was located on a plasmid of approximately 55 kb and could
      be transferred to Escherichia coli J53. MLST analysis showed that this strain
      belonged to an uncommon sequence type ST1224. CONCLUSION: The coexistence of
      various resistant genes is the mechanism for resistance to most antibiotics.
      Additionally, infections caused by multi-drug resistant bacteria increase the
      mortality of patients with immunodeficiency, which alerts clinicians to establish
      a rational and effective combination drug therapy.

PMID- 28490009
TI  - Clinicopathologic Study of Biliary Intraepithelial Neoplasia in
      Cholangiocarcinoma.
AB  - BACKGROUNDS AND AIMS: Biliary intraepithelial neoplasia (BilIN) is a precursor of
      cholangiocarcinoma (CC) and it has been associated with several chronic
      inflammatory conditions. This study aimed to elucidate the prevalence of BilIN in
      CC and its clinicopathological significance. METHODS: Medical records of 193
      patients with histologically confirmed CC were analyzed. We reviewed the
      pathology findings of 48 patients who underwent curative surgery for CC. RESULTS:
      Of the 48 patients analyzed, 34 and 14 patients had extrahepatic and intrahepatic
      CC respectively. BilIN was detected in 28 patients (58%) and showed a
      significantly higher prevalence in extrahepatic CC (75%) than in intrahepatic CC
      (21%; p < 0.001). In the subgroup of 34 patients with extrahepatic CC, 25 and 9
      patients were BilIN positive and negative respectively. Poor differentiation and
      T3 stage were significantly more common in the BilIN-negative group than in the
      BilIN-positive group (p < 0.05). The expression of MUC5AC, p53, and loss of Smad4
      showed no difference between BilIN-positive CC and in BilIN-negative CC, but the
      Ki-67 expression was significantly higher (p < 0.05). CONCLUSION: BilIN-positive
      CC showed less invasiveness than negative cases. The Ki-67 expression was
      significantly higher in BilIN-positive CC.

PMID- 28490010
TI  - A Novel Approach of Synthesizing and Evaluating the Anticancer Potential of
      Silver Oxide Nanoparticles in vitro.
AB  - BACKGROUND: Development of novel strategies to kill cancer by sparing normal
      cells is of utmost importance. Apart from their known antimicrobial activity,
      only limited information has been recorded regarding the antitumor potential of
      biocompatible silver oxide nanoparticles (AgONPs). There is a need to evaluate
      the anticancer potential of biocompatible AgONPs in vitro. METHODS: A new
      approach of utilizing the leaf extract of Excoecaria agallocha was used to
      synthesize AgONPs. This was then characterized by ultraviolet-visible
      spectrophotometry, nanoparticle-tracking analysis, and zeta-potential analysis.
      Cytotoxicity and apoptotic potential were evaluated with an MTT assay and an
      annexin V-binding assay against the murine melanoma (B16F10), murine colon cancer
      (CT26), murine lung adenocarcinoma (3LL), and murine Ehrlich ascites carcinoma
      (EAC) cell lines. Cellular localization of AgONPs was evaluated on fluorescence
      microscopy. RESULTS: UV peaks at 270 and 330 nm indicated the formation of
      nanoparticles (NPs) and the NP-tracking analyzer revealed them to have a size of
      228 nm. AgONPs exerted initial cytotoxicity, specifically against all the
      experimental malignant cells by sparing the normal cell lines. Moreover, AgONPs
      exert apoptosis equally on all the malignant cells in vitro and ex vivo. This
      cytotoxicity possibly occurs via the nuclear translocation of AgONPs as analyzed
      in B16F10 cells. CONCLUSIONS: AgONPs utilizing natural sources would be a new
      medicinal approach against a broad spectrum of malignancy.

PMID- 28490011
TI  - New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible
      Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone
      Erosions.
AB  - OBJECTIVES: New interleukins (ILs), especially members of IL-1 and IL-12
      families, have recently been reported to be involved in the development and
      regulation of autoimmune and inflammatory diseases. In this study, we aimed to
      explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis
      (PsA). METHODS: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs)
      were recruited. Blood samples were obtained for detecting the levels of ILs, IL
      12/23p40, and tumor necrosis factor alpha (TNF-alpha). The severity of skin
      lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis
      activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA
      patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and
      receptor activator of nuclear factor-kappaB ligand) and numbers of osteoclast
      precursors were evaluated. Radiographic features of affected joints in these
      patients were scored for erosion, joint-space narrowing, osteolysis, and new bone
      formation. Correlations among levels of these ILs, Ps, and PsA disease activities
      and bone erosions were studied. RESULTS: Ps and PsA patients had higher serum
      levels of TNF-alpha, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were
      higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had
      higher serum levels of IL-36alpha and IL-38 than patients with Ps vulgaris or
      HCs. Increased serum levels of IL-36alpha were positively correlated with PASI.
      CONCLUSION: Certain ILs were elevated in the circulation of patients with Ps and
      PsA, which might contribute to the pathogenesis of skin lesions and arthritis.

PMID- 28490012
TI  - Is the Prophylactic Use of Hepatoprotectants Necessary in Anti-Tuberculosis
      Treatment?
AB  - BACKGROUND: Liver injury is one of the serious side effects of anti-tuberculosis
      (TB) drugs. It is controversial whether hepatoprotectant prophylaxis is efficient
      and safe in anti-TB treatment, so we aimed to assess the efficacy and safety of
      hepatoprotectant prophylaxis in patients who had received anti-TB treatment.
      METHODS: PubMed, the Cochrane library, Embase, Ovid, Springer link, Wiley,
      Elsevier, Web of Science, and the Karger Online Journal were systematically
      searched prior to April 2016 for articles related to hepatoprotectant prophylaxis
      in the treatment of TB. A meta-analysis was conducted to estimate the effect of
      hepatoprotective agents on liver function and adverse events (AEs) in patients
      who had received anti-TB drugs. The primary outcomes were changes in alanine
      transaminase (ALT) and aspartate transaminase (AST) levels. The other outcomes
      were drug-induced liver injury (DILI) and AEs. RESULTS: In our review, 6 trials
      that involved 1,227 patients were included. Our analysis indicated that
      hepatoprotective agents exerted protective effects on liver function in patients
      who had received anti-TB drugs (weighted mean difference, WMD = -7.81, 95% CI [
      12.26, -3.37], p = 0.0006 [ALT]; WMD = -7.07, 95% CI [-11.43, -2.72], p = 0.001
      [AST]) in any age group. However, in the subgroup analysis of treatment duration,
      the use of hepatoprotective agents was not associated with significant changes in
      ALT and AST levels after 2 weeks of treatment and exhibited a positive effect on
      liver function after 4 weeks of treatment. Moreover, the use of hepatoprotectants
      significantly decreased the number of DILI cases (risk ratio, RR 0.50, 95% CI
      [0.34-0.73], p = 0.0004). However, the use of hepatoprotectants led to similar
      AEs in the control groups (RR 1.07, 95% CI [0.82-1.39], p = 0.62). CONCLUSIONS:
      The use of hepatoprotective drugs may prevent liver injury in patients who are
      receiving anti-TB drugs without any significant AEs 4 weeks after the initiation
      of hepatoprotective medication.

PMID- 28490013
TI  - Sulfatase 2 Modulates Fate Change from Motor Neurons to Oligodendrocyte Precursor
      Cells through Coordinated Regulation of Shh Signaling with Sulfatase 1.
AB  - Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2,
      which specifically remove sulfate from heparan sulfate proteoglycans. Although
      several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh)
      signaling during embryonic ventral spinal cord development, the detailed
      expression pattern and function of Sulf2 in the spinal cord remains to be
      determined. In this study, we found that Sulf2 also modulates the cell fate
      change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by
      regulating Shh signaling in the mouse ventral spinal cord in coordination with
      Sulf1. In the mouse, Sulf mRNAs colocalize with Shh mRNA and gradually expand
      dorsally from embryonic day (E) 10.5 to E12.5, following strong Patched1 signals
      (a target gene of Shh signaling). This coordinated expression pattern led us to
      hypothesize that in the mouse, strong Shh signaling is induced when Shh is
      released by Sulf1/2, and this strong Shh signaling subsequently induces the
      dorsal expansion of Shh and Sulf1/2 expression. Consistent with this hypothesis,
      in the ventral spinal cord of Sulf1 knockout (KO) or Sulf2 KO mice, the
      expression patterns of Shh and Patched1 differed from that in wild-type mice.
      Moreover, the position of the pMN and p3 domains were shifted ventrally, MN
      generation was prolonged, and OPC generation was delayed at E12.5 in both Sulf1
      KO and Sulf2 KO mice. These results demonstrated that in addition to Sulf1, Sulf2
      also plays an important and overlapping role in the MN-to-OPC fate change by
      regulating Shh signaling in the ventral spinal cord. However, neither Sulf1 nor
      Sulf2 could compensate for the loss of the other in the developing mouse spinal
      cord. In vitro studies showed no evidence of an interaction between Sulf1 and
      Sulf2 that could increase sulfatase activity. Furthermore, Sulf1/2 double
      heterozygote and Sulf1/2 double KO mice exhibited phenotypes similar to the Sulf1
      KO and Sulf2 KO mice. These results indicate that there is a threshold for
      sulfatase activity (which is likely reflected in the dose of Shh) required to
      induce the MN-to-OPC fate change, and Shh signaling requires the coordinated
      activity of Sulf1 and Sulf2 in order to reach that threshold in the mouse ventral
      spinal cord.

PMID- 28490014
TI  - Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic
      Toxins.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      involved in the expression of xenobiotic-metabolizing enzymes, inflammatory
      cytokines and adhesion molecules. Uremic toxins such as indoxyl sulfate and
      indole acetic acid are derived from tryptophan fermentation by gut microbiota;
      they accumulate in patients with chronic kidney disease (CKD) on haemodialysis
      and have recently emerged as potent ligands of AhR. Therefore, AhR can serve as a
      mediator in inflammation and cardiovascular diseases in these patients. This
      review discusses current data that support a link between AhR activation and
      uremic toxins from gut microbiota in CKD.

PMID- 28490015
TI  - Salidroside Attenuates Ventilation Induced Lung Injury via SIRT1-Dependent
      Inhibition of NLRP3 Inflammasome.
AB  - BACKGROUND: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea
      L with a variety of pharmacologic properties. We aim to investigate the effects
      of SDS on ventilation induced lung injury (VILI) and explore the possible
      underlying molecular mechanism. METHODS: Lung injury was induced in male ICR mice
      via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four
      groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation
      with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before
      operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to
      cyclic stretch for 4h. RESULTS: It was found that SDS attenuated VILI as shown in
      HE staining, cell count and protein content levels in BAL fluid, W/D and Evans
      blue dye leakage into the lung tissue. SDS treatment inhibited the activation of
      NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)
      1beta secretion both in vivo and in vitro. Moreover, SDS administration up
      regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the
      inhibitory effect of SDS on NLRP3 inflammasome activation. CONCLUSIONS: Taken
      together, these findings indicate that SDS may confer protection against
      ventilation induced lung injury via SIRT1-de-pendent inhibition of NLRP3
      inflammasome activation.

PMID- 28490016
TI  - Backup Mechanisms Maintain PACAP/VIP-Induced Arterial Relaxations in Pituitary
      Adenylate Cyclase-Activating Polypeptide-Deficient Mice.
AB  - BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a
      multifunctional neuropeptide in the VIP/secretin/glucagon peptide superfamily.
      Two active forms, PACAP1-38 and PACAP1-27, act through G protein-coupled
      receptors, the PAC1 and VPAC1/2 receptors. Effects of PACAP include potent
      vasomotor activity. Vasomotor activity and organ-specific vasomotor effects of
      PACAP-deficient mice have not yet been investigated; thus, the assessment of its
      physiological importance in vasomotor functions is still missing. We hypothesized
      that backup mechanisms exist to maintain PACAP pathway activity in PACAP knockout
      (KO) mice. Thus, we investigated the vasomotor effects of exogenous vasoactive
      intestinal peptide (VIP) and PACAP polypeptides in PACAP wild-type (WT) and PACAP
      deficient (KO) male mice. METHODS: Carotid and femoral arteries were isolated
      from 8- to 12-week-old male WT and PACAP-KO mice. Vasomotor responses were
      measured with isometric myography. RESULTS: In the arteries of WT mice the
      peptides induced relaxations, which were significantly greater to PACAP1-38 than
      to PACAP1-27 and VIP. In KO mice, PACAP1-38 did not elicit relaxation, whereas
      PACAP1-27 and VIP elicited significantly greater relaxation in KO mice than in WT
      mice. The specific PAC1R and VPAC1R antagonist completely blocked the PACAP
      induced relaxations. CONCLUSION: Our data suggest that in PACAP deficiency,
      backup mechanisms maintain arterial relaxations to polypeptides, indicating an
      important physiological role for the PACAP pathway in the regulation of vascular
      tone.

PMID- 28490017
TI  - Using Borderline Personality Organization to Predict Outcome after Total Knee
      Arthroplasty.

PMID- 28490018
TI  - Conflicts of Interest and the Presence of Methodologists on Guideline Development
      Panels: A Cross-Sectional Study of Clinical Practice Guidelines for Major
      Depressive Disorder.

PMID- 28490019
TI  - Serious Games: The Future of Psychotherapy? Proposal of an Integrative Model.

PMID- 28490020
TI  - Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta
      and Fetal Brain.
AB  - Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric
      disorders such as cerebral palsy, schizophrenia, and autism. We had previously
      shown that intrauterine inflammation resulted in a decrease in serotonin, one of
      the tryptophan metabolites, and a decrease in serotonin fibers in the sensory
      cortex of newborns in a rabbit model of cerebral palsy. In this study, we
      hypothesized that maternal inflammation results in alterations in tryptophan
      pathway enzymes and metabolites in the placenta and fetal brain. We found that
      intrauterine endotoxin administration at gestational day 28 (G28) resulted in a
      significant upregulation of indoleamine 2,3-dioxygenase (IDO) in both the
      placenta and fetal brain at G29 (24 h after treatment). This endotoxin-mediated
      IDO induction was also associated with intense microglial activation, an increase
      in interferon gamma expression, and increases in kynurenine and the kynurenine
      pathway metabolites kynurenine acid and quinolinic acid, as well as a significant
      decrease in 5-hydroxyindole acetic acid (a precursor of serotonin) levels in the
      periventricular region of the fetal brain. These results indicate that maternal
      inflammation shunts tryptophan metabolism away from the serotonin to the
      kynurenine pathway, which may lead to excitotoxic injury along with impaired
      development of serotonin-mediated thalamocortical fibers in the newborn brain.
      These findings provide new targets for prevention and treatment of maternal
      inflammation-induced fetal and neonatal brain injury leading to
      neurodevelopmental disorders such as cerebral palsy and autism.

PMID- 28490021
TI  - Alexithymia and Psychotherapeutic Treatment Motivation: Main and Interactional
      Effects on Treatment Outcome.

PMID- 28490022
TI  - Concurrent Treatment with Prolonged Exposure for Co-Occurring Full or
      Subthreshold Posttraumatic Stress Disorder and Substance Use Disorders: A
      Randomized Clinical Trial.
AB  - BACKGROUND: To test whether an integrated prolonged exposure (PE) approach could
      address posttraumatic stress disorder (PTSD) symptoms effectively in individuals
      with co-occurring substance use disorders (SUD), we compared concurrent treatment
      of PTSD and SUD using PE (COPE) to relapse prevention therapy (RPT) for SUD and
      an active monitoring control group (AMCG). METHODS: We conducted a randomized 12
      week trial with participants (n = 110; 64% males; 59% African Americans) who met
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text
      revision criteria for full or subthreshold PTSD and SUD. Participants were
      randomly assigned to COPE (n = 39), RPT (n = 43), or AMCG (n = 28). RESULTS: At
      the end-of-treatment, COPE and RPT demonstrated greater reduction in PTSD symptom
      severity relative to AMCG (COPE-AMCG = -34.06, p < 0.001; RPT-AMCG = -22.58, p =
      0.002). Although the difference between COPE and RPT was not significant in the
      complete sample, the subset of participants with full (vs. subthreshold) PTSD
      demonstrated significantly greater reduction of PTSD severity in COPE relative to
      RPT. Both treatments were superior to AMCG in reducing the days of primary
      substance use (COPE-AMCG = -0.97, p = 0.01; RPT-AMCG = -2.07, p < 0.001).
      Relative to COPE, RPT showed significantly more improvement in SUD outcome at end
      of-treatment (RPT-COPE = -1.10, p = 0.047). At 3-month follow-up, COPE and RPT
      maintained their treatment gains and were not significantly different in PTSD
      severity or days of primary substance use. CONCLUSION: COPE and RPT reduced PTSD
      and SUD severity in participants with PTSD + SUD. Findings suggest that among
      those with full PTSD, COPE improves PTSD symptoms more than a SUD-only treatment.
      The use of PE for PTSD was associated with significant decreases in PTSD symptoms
      without worsening of substance use.

PMID- 28490023
TI  - Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in
      Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.
AB  - Activation of the inflammatory pathway is increasingly recognized as an important
      mechanism of injury following neonatal asphyxia and encephalopathy. This process
      may contribute to the poor prognosis seen in some cases, despite therapeutic
      hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL
      16, measured in umbilical cord blood at birth, to be predictive of grade of
      hypoxic-ischaemic encephalopathy (HIE). Our aim in this study was to examine the
      ability of these cytokines to predict the 3-year neurodevelopmental outcome in
      the same cohort. As part of a prospective, longitudinal cohort study set in a
      single tertiary maternity unit, term infants with biochemical and clinical
      evidence of perinatal asphyxia were recruited at birth. Umbilical cord blood was
      collected and analyzed for IL-6 and IL-16 using a Luminex assay. The
      neurodevelopmental outcome of these infants was assessed at 3 years using the
      Bayley Scales of Infant and Toddler Development (Edition 3). Early cord blood
      measurement of IL-6 and IL-16 and long-term outcome were available in 33/69
      infants. Median (IQR) IL-16 differentiated infants with a severely abnormal
      outcome (n = 6) compared to all others (n = 27), (646 [466-1,085] vs. 383.5 [284
      494] pg/mL; p = 0.012). IL-16 levels were able to predict a severe outcome with
      an area under the receiver-operating characteristic (ROC) curve of 0.827 (95% CI
      0.628-1.000; p = 0.014). Levels >=514 pg/mL predicted a severe outcome with a
      sensitivity of 83% and a specificity of 81%. IL-16 also outperformed other
      routine biochemical markers available at birth for the prediction of severe
      outcome. APGAR scores at 1 and 10 min were also predictive of a severe outcome (p
      = 0.022 and p = 0.036, respectively). A combination of IL-16 with these clinical
      markers did not improve predictive value, but IL-16 combined with
      electroencephalogram grading increased the area under the ROC curve. IL-6 did not
      show any association with 3-year outcome. This is the first report studying the
      association of IL-16 measured at birth with long-term outcome in a cohort of
      neonates with perinatal asphyxia. IL-16 may be an early biomarker of severe
      injury and aid in the long-term prognostication in infants with HIE.

PMID- 28490024
TI  - A Novel Ataxic Mutant Mouse Line Having Sensory Neuropathy Shows Heavy Iron
      Deposition in Kidney.
AB  - BACKGROUND/AIMS: A novel ataxic mouse line was established from the offspring of
      a male mouse administered cyclophosphamide in a juvenile period. METHODS: We have
      attempted to examine the phenotype and histopathological changes of affected
      mice. Furthermore, linkage analysis and sequencing of the mutant was performed to
      reveal the causative gene locus. RESULTS AND CONCLUSION: The affected mouse was
      characterized by heavy hind limb ataxia with gait disorder, which was first
      recognized at about 4 weeks of age and slowly progressed with advancing age. The
      phenotype was inherited in an autosomal recessive pattern. The genetic locus
      associated with the phenotype was named hak and mapped to 107,305,356-108,637,615
      on chromosome 2qE3, non-coding sequences in the vicinity of Bdnf gene. Many
      spheroids were noticed in the cerebellar medulla and the brain stem. In the
      peripheral nerves, some sensory ganglionic cells showed deposition of NF-200 in
      the perikaryon and NF-200-positive spheroids in nerve fibers. No inflammatory
      cell infiltration was observed. In addition, the adult affected mouse had
      distinct iron deposition in the kidney and the liver, but not in the heart, the
      skeletal muscle and the central nervous system. These results suggest that the
      hak mouse has a tissue-specific impairment in the expression of a type of Bdnf
      transcripts.

PMID- 28490025
TI  - Group Cognitive Behavior Therapy Reversed Abnormal Spontaneous Brain Activity in
      Adult Asthmatic Patients.

PMID- 28490026
TI  - Cervical Esophagotomy for Removal of an Ingested Clam Shell: A Very Uncommon
      Foreign Body Ingestion.
AB  - OBJECTIVE: To report the removal of an ingested clam shell that was firmly
      impacted in the esophagus. CLINICAL PRESENTATION AND INTERVENTION: A 77-year-old
      man presented at our hospital with acute dysphagia after eating a seafood
      risotto. An urgent dedicated examination (noncontrast helical multislice computed
      tomography scan of the neck and flexible esophagoscopy) detected a clam shell
      lodged in the upper esophagus. After several unsuccessful endoscopic attempts, a
      lifesaving cervical esophagotomy was performed and the foreign body was
      retrieved. CONCLUSION: This patient who ingested clam shell recovered well
      following the retrieval of the foreign body by performing a lifesaving cervical
      esophagotomy.

PMID- 28490027
TI  - The Missed Diagnosis and Misdiagnosis of Pediatric Obesity.

PMID- 28490028
TI  - Can We Jump from Cross-Sectional to Dynamic Interpretations of Networks?
      Implications for the Network Perspective in Psychiatry.

PMID- 28490029
TI  - Altered Dopamine Responses to Monetary Rewards in Female Fibromyalgia Patients
      with and without Depression: A [11C]Raclopride Bolus-plus-Infusion PET Study.

PMID- 28490030
TI  - Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous
      Ketamine in Treatment-Resistant Depression.
AB  - INTRODUCTION: Ketamine has shown rapid though short-lived antidepressant effects.
      The possibility of concerning neurobiological changes following repeated exposure
      to the drug motivates the development of strategies that obviate or minimize the
      need for longer-term treatment with ketamine. In this open-label trial, we
      investigated whether cognitive behavioral therapy (CBT) can sustain or extend
      ketamine's antidepressant effects. METHODS: Patients who were pursuing ketamine
      infusion therapy for treatment-resistant depression were invited to participate
      in the study. If enrolled, the subjects initiated a 12-session, 10-week course of
      CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine
      (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol.
      RESULTS: Sixteen participants initiated the protocol, with 8 (50%) attaining a
      response to the ketamine and 7 (43.8%) achieving remission during the first 2
      weeks of protocol. Among ketamine responders, the relapse rate at the end of the
      CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On
      longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to
      relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3
      of 7 retained remission until at least 4 weeks following the last ketamine
      exposure, with 2 retaining remission through 8 weeks following ketamine exposure.
      Ketamine nonresponders did not appear to benefit from CBT. CONCLUSIONS: CBT may
      sustain the antidepressant effects of ketamine in treatment-resistant depression.
      Well-powered randomized controlled trials are warranted to further investigate
      this treatment combination as a way to sustain ketamine's antidepressant effects.

PMID- 28490031
TI  - A Systematic Review of the Clinimetric Properties of the 6-Item Version of the
      Hamilton Depression Rating Scale (HAM-D6).
AB  - BACKGROUND: In a study aimed at identifying the items carrying information
      regarding the global severity of depression, the 6-item Hamilton Depression
      Rating Scale (HAM-D6) was derived from the original 17-item version of the scale
      (HAM-D17). Since then, the HAM-D6 has been used in a wide range of clinical
      studies. We now provide a systematic review of the clinimetric properties of HAM
      D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression
      Rating Scale (MADRS). METHODS: We conducted a systematic search of the literature
      in PubMed, PsycInfo, and EMBASE databases in accordance with the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guideline. Studies
      reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17
      or MADRS in non-psychotic unipolar or bipolar depression were included in the
      synthesis. RESULTS: The search identified 681 unique records, of which 51
      articles met the inclusion criteria. According to the published literature, HAM
      D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability
      (each item contains unique information regarding syndrome severity),
      transferability (scalability is constant over time and irrespective of sex, age,
      and depressive subtypes), and responsiveness (sensitivity to change in severity
      during treatment). CONCLUSIONS: According to the published literature, the
      clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and
      MADRS. Since the validity of HAM-D6 has been demonstrated in both research and
      clinical practice, using the scale more consistently would facilitate translation
      of results from one setting to the other.

PMID- 28490033
TI  - "Salami Slicing" in Pooled Analyses of Second-Generation Antipsychotics for the
      Treatment of Depression.

PMID- 28490032
TI  - Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer.
AB  - BACKGROUND/AIMS: In mammalian cells, XRCC3 plays an important role in the DNA
      double-strand breaks (DSBs) repair by homologous recombination. Genetic
      polymorphisms in XRCC3 gene may potentially affect the repair of DSBs and thus
      confer susceptibility to thyroid cancer. In this study, we used a haplotype-based
      approach to investigate whether 5 selected SNPs i.e. rs1799796, rs1799794,
      rs861539, rs709399 and rs861530 of XRCC3 gene are associated with thyroid cancer
      risk in 456 cancer patients and 400 cancer-free controls. METHODS: Genotyping was
      performed using Allele-specific PCR followed by sequencing. Statistical analysis
      was performed to analyse gene and haplotype association. RESULTS: After analysis,
      frequency of mutant genotype/alleles of SNPs (rs1799796, p<0.0001; rs1799794,
      p<0.0001; rs861539, p<0.001; rs709399, p <0.0001; rs861530, p<0.002) was found
      significantly higher in thyroid cancer patients compared to controls. Significant
      associations were found for most of the variant genotypes in SNPs of rs1799794,
      rs1799796, rs861539, rs861530 and rs709399 in papillary thyroid and follicular
      cancer patients compared to other histologic subtypes of thyroid carcinoma.
      Additionally, haplotype analysis revealed that haplotypes, AACGA (p= 0.0005),
      AGTAA (p= 0.008), GATAA (p= 0.001), GGCAA (p= 0.001) were linked with significant
      increase in thyroid cancer risk. However, haplotype AGCGG (p= 0.0009) was
      associated with a significant reduced thyroid cancer risk. CONCLUSION: Our
      results suggest that common genetic variants in the XRCC3 gene of DSBR pathway
      may modulate thyroid cancer risk.

PMID- 28490034
TI  - Long Noncoding RNA CRNDE Promotes Proliferation of Gastric Cancer Cells by
      Targeting miR-145.
AB  - BACKGROUND/AIMS: The colorectal neoplasia differentially expressed (CRNDE) gene
      is a long noncoding RNA (lncRNAs) that is upregulated in colorectal cancer and
      glioma. Here, we investigated the regulatory function of CRNDE in gastric cancer
      (GC). METHODS: CRNDE and miR-145 expression were assayed by qRT-PCR, and E2F3
      protein expression was measured by western blotting. A luciferase reporter assay
      was used to detect the direct regulation of miR-145 by CRNDE. Cell viability and
      colony formation of human GC cells were detected using MTT and colony formation
      assay, respectively. RESULTS: CRNDE was highly expressed in GC cell lines and
      tissues; overexpression of CRNDE increased GC cell viability and promoted colony
      formation. Knockdown of CRNDE did not result in loss of expression-related
      effects on cell proliferation and colony formation. Further investigation
      revealed that the miR-145 target gene E2F3 was strongly expressed following CRNDE
      competitive molecular sponging of miR-145. CONCLUSION: CRNDE acted as a growth
      promoting lncRNA in GC and maybe a potential target of GC treatment.

PMID- 28490035
TI  - Clinical Pharmacopsychology: Conceptual Foundations and Emerging Tasks.
AB  - The aim of this critical review was to outline emerging trends and perspectives
      of clinical pharmacopsychology, an area of clinical psychology that is concerned
      with the psychological effects of medications. The historical development of
      clinical pharmacopsychology is outlined, with discussion of its most
      representative expressions and reference to current challenges of clinical
      research, with particular reference to clinimetrics. The domains of clinical
      pharmacopsychology encompass the clinical benefits of psychotropic drugs, the
      characteristics that predict responsiveness to treatment, the vulnerabilities
      induced by treatment (side effects, behavioral toxicity, iatrogenic comorbidity),
      and the interactions between drug treatment and psychological variables. Its aim
      is to provide a comprehensive assessment of the clinical important changes that
      are concerned with (a) wanted and expected treatment effects, (b) treatment
      induced unwanted side effects, and (c) the patient's own personal experience of a
      change in terms of well-being and/or quality of life. Clinical pharmacopsychology
      offers a unifying framework for the understanding of clinical phenomena in
      medical and psychiatric settings. Research in this area deserves high priority.

PMID- 28490036
TI  - Fractured Penis: Not So Rare!
AB  - INTRODUCTION: Penile fracture is a relatively common phenomenon. The main problem
      associated with this condition is the lack of patients' awareness on the urgency
      of the situation. This study reports the different modes of presentations and
      treatment results. MATERIALS AND METHODS: We reviewed 21 cases of penile fracture
      over 5 years. Parameters were mode of injury, age group, time interval before
      presentation, management, site of injury, urethral involvement, results,
      complications and erectile function at follow-up. RESULTS: The mean age of
      patients was 34 years, the mean time interval until presentation was 26 h. Cases
      involving the right corpus cavernosum comprised 57.14% and 42.85% were cases
      involving the left corpus cavernosum. Two patients had full circumferential
      urethral tear. Two patients developed wound infections and 2 patients developed
      mild penile curvature (<30 degrees ). These 4 patients had all presented late for
      treatment (>40 h). CONCLUSION: Urologists need to consider penile fracture a
      urological emergency and atypical presentations need to be considered when
      deciding on management.

PMID- 28490037
TI  - Cyberchondria: Challenges of Problematic Online Searches for Health-Related
      Information.

PMID- 28490038
TI  - Pediatric sleep-disordered breathing: an update on diagnostic testing.
AB  - PURPOSE OF REVIEW: Recent advances in diagnostic testing for obstructive sleep
      apnea in children have refined the standard tests while identifying several new
      tools that hold promise to radically change how we diagnose sleep apnea. RECENT
      FINDINGS: Studies have demonstrated that the polysomnogram may be modified to
      permit home assessment of sleep disturbed breathing in children to ensure more
      widespread access to the test. Alternately, questionnaires, nocturnal oximetry,
      and diagnostic urinary biomarkers have shown great promise as both sensitive and
      specific tools to diagnose sleep apnea in children as well as track the severity
      of the disease. SUMMARY: The gold standard polysomnogram has been refined to
      permit its application in a modified form at home and for brief examinations in
      children. This standard has been challenged on several fronts, including
      questionnaires, nocturnal oximetry, drug-induced sleep endoscopy, and noninvasive
      urinary biomarkers that may ultimately supplant polysomnography as the gold
      standard to diagnose obstructive sleep apnea syndrome in children.

PMID- 28490039
TI  - The implications of immunization in the daily practice of pediatric anesthesia.
AB  - PURPOSE OF REVIEW: Vaccination is an important prevention measure, but requires
      an intact immune system. Surgery and anesthesia suppress the immune system and
      may interfere with the benefits of immunization. Moreover, common vaccine side
      effects may be misinterpreted as postsurgical complications. This review
      summarizes the essential basis of immunization and its potential interactions
      with anesthesia. RECENT FINDINGS: Vaccines have mild side-effects, such as fever,
      but may lead to serious complications in immunocompromised patients. Surgery and
      anesthesia may decrease the efficacy of a vaccine, or promote vaccine-related
      complications. It, therefore, reasonable to schedule surgery and anesthesia with
      a delay either before or after vaccine administration, but there is no consensus
      among anesthesiologists and pediatricians regarding this timing. SUMMARY:
      Inactive vaccines are generally well tolerated. Live vaccines provide an
      effective and long-lasting immunization, but may carry more serious
      complications. Elective operations should be postponed 1 week after an inactive
      vaccine and 3 weeks after immunization with a live vaccine. To avoid
      misinterpretation of vaccine-related side-effects, vaccination should be also
      delayed after surgery.

PMID- 28490040
TI  - Individualized Plastic Reconstruction Strategy for Patients With Ectodermal
      Dysplasia Syndrome.
AB  - Ectodermal dysplasia syndrome is a hereditary disease of ectodermal origin.
      Appearances of nail dystrophy, alopecia or hypotrichosis, saddle nose deformity,
      and palmoplantar hyperkeratosis are usually associated with a lack of sweat
      glands as well as partial or complete absence of teeth. These manifestations are
      usually corrected only with oral rehabilitation by mounting dentures. In this
      study, plastic rehabilitation was developed to correct the special features of
      patients with ectodermal dysplasia. Four men and 1 woman with ectodermal
      dysplasia syndrome were treated. Four patients showed dysostosis of the midface,
      and rhinoplasty with costal bone was performed, whereas cosmetic operation aiming
      to repair soft tissue defects was adopted for the last patient. After plastic
      corrections, all 5 patients were satisfied with the results and had no social
      embarrassment.

PMID- 28490041
TI  - Hair Transplantation on a Free Microvascular Latissimus Dorsi Flap. Case Report:
      Erratum.

PMID- 28490042
TI  - Reply to "Different Ideas of Nodal Grouping in Standard and Extended
      Lymphadenectomy During Pancreaticoduodenectomy for Pancreatic Head Cancer".

PMID- 28490043
TI  - Chemical and Physical Exposures in the Emerging US Green-Collar Workforce.
AB  - OBJECTIVE: "Green collar" workers serve in occupations that directly improve
      environmental quality and sustainability. This study estimates and compares the
      prevalence of select physical and chemical exposures among green versus non-green
      U.S. workers. METHODS: Data from the U.S. 2010 National Health Interview Survey
      (NHIS) Occupational Health Supplement were linked to the Occupational Information
      Network (ONET) Database. We examined four main exposures: 1) vapors, gas, dust,
      fumes (VGDF); 2) secondhand tobacco smoke; 3) skin hazards; 4) outdoor work.
      RESULTS: Green-collar workers were significantly more likely to report exposure
      to VGDF and outdoor work than nongreen-collar workers [adjusted odds ratio (AOR)
      = 1.25; 95% CI = 1.11 to 1.40; AOR = 1.44 (1.26 to 1.63), respectively]. Green
      collar workers were less likely to be exposed to chemicals (AOR = 0.80; 0.69 to
      0.92). CONCLUSIONS: Green-collar workers appear to be at a greater risk for
      select workplace exposures. As the green industry continues to grow, it is
      important to identify these occupational hazards in order to maximize worker
      health.

PMID- 28490044
TI  - Dual Infection Contributes to Rapid Disease Progression in Men Who Have Sex With
      Men in China.
AB  - BACKGROUND: Considerable numbers of HIV-1-infected men who have sex with men
      (MSM) show a relatively rapid disease progression in China; however, the cause
      remains elusive. HIV-1 dual infection was reported to occur commonly among the
      MSM population, and its contribution to clinical prognosis remains controversial.
      We investigated the occurrence and impact on disease progression of dual
      infection in a prospective MSM cohort in China. METHODS: Sixty-four HIV-1 early
      infected participants were longitudinally followed up for 2 years. Deep
      sequencing was used as dual-infection screening. CD4 T-cell counts and HIV-1
      viral load were compared between coinfection and single-infection participants
      and pre- versus post-superinfection. RESULTS: Eight coinfected participants and
      10 superinfected participants were identified, including 9 participants with
      intersubtype and 9 with intrasubtype dual infections. The prevalence of
      coinfection was 13.1%, with a superinfection incidence of 15.6%. Coinfection
      participants showed lower CD4 T-cell counts at 120 days after infection (P =
      0.042) and a higher viral set point tendency (P = 0.053) as compared with single
      infection participants. Kaplan-Meier analysis showed that the time for the viral
      load to increase to above 4 log10 copies per milliliter was shorter in
      coinfection participants than in single-infection participants (P < 0.001). After
      superinfection, the median CD4 T-cell count decreased from 635 to 481 cells/MUL
      (P = 0.027). CONCLUSIONS: The occurrence of dual infection among Chinese MSM is
      relatively high, and HIV-1 dual infection might contribute to rapid disease
      progression seen in the MSM population.

PMID- 28490045
TI  - Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With
      IGFBP5 and THBS1.
AB  - Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites,
      including the uterus. Like its soft tissue counterpart, uterine IMT frequently
      expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to
      fully characterize the genetic fusions that occur in uterine IMT. We studied 11
      uterine IMTs with typical histology and 8 uterine myxoid smooth muscle tumors (5
      leiomyomas, 1 smooth muscle tumor of uncertain malignant potential, and 2
      leiomyosarcomas) in which the differential of IMT was considered, using a RNA
      sequencing-based fusion assay to detect genetic fusions involving ALK, ROS1, RET,
      NTRK1/3, and other genes. ALK was expressed in 10 of 11 IMTs and 1 tumor
      initially categorized as a myxoid leiomyoma (granular cytoplasmic staining with
      paranuclear accentuation). Fusion transcripts involving ALK were identified in 9
      of 10 ALK immunopositive IMTs, with 3 harboring IGFBP5-ALK, 3 harboring THBS1
      ALK, 2 harboring FN1-ALK, and 1 harboring TIMP3-ALK. Among the smooth muscle
      tumors, IGFBP5-ALK fusion transcript was identified in only 1 ALK immunopositive
      case. Further review revealed that although a diagnosis of IMT was considered for
      the ALK immunopositive myxoid leiomyoma, this diagnosis was not initially
      rendered only because fluorescence in situ hybridization analysis was interpreted
      as negative for ALK genetic rearrangement; this case is best reclassified as an
      IMT. Notably, all the ALK fusions identified in our study included the
      transmembrane domain-encoding exon 19 of ALK. Our findings confirm the high
      frequency of ALK fusions in uterine IMT, with an enrichment of novel 5' ALK
      fusion partners (IGFBP5, THBS1, and TIMP3) and exon 19-containing ALK fusion.
      Given that IGFBP5 and FN1 are both situated on the same chromosome as ALK,
      fluorescence in situ hybridization analysis for ALK rearrangement may not be
      reliable and a negative result should not exclude a diagnosis of uterine IMT if
      the histologic features and ALK immunostaining findings are supportive.

PMID- 28490047
TI  - Development and Validation of an LC-MS/MS Method for the Simultaneous
      Quantification of Abiraterone, Enzalutamide, and Their Major Metabolites in Human
      Plasma.
AB  - BACKGROUND: Abiraterone acetate and enzalutamide are 2 novel drugs for the
      treatment of metastatic castration-resistant prostate cancer. The metabolism of
      these drugs is extensive. Major metabolites are N-desmethyl enzalutamide,
      enzalutamide carboxylic acid, abiraterone N-oxide sulfate, and abiraterone
      sulfate; of which N-desmethyl enzalutamide is reported to possess antiandrogen
      capacities. A liquid chromatography-tandem mass spectrometry method for
      simultaneous quantification of abiraterone, enzalutamide, and the main
      metabolites has been developed and validated to support therapeutic drug
      monitoring. METHODS: Human plasma samples of patients treated with abiraterone or
      enzalutamide were harvested at the clinic and stored at -20 degrees C. Proteins
      were precipitated by acetonitrile, and the final extract was injected on a
      Kinetex C18 column and separated with gradient elution. Analytes were detected by
      liquid chromatography-mass spectrometry (Triple Quad 6500). RESULTS: The method
      was validated over various linear ranges: 1-100 ng/mL for abiraterone, 5-500
      ng/mL for enzalutamide and enzalutamide carboxylic acid, 10-1000 ng/mL for N
      desmethyl enzalutamide, 30-3000 ng/mL for abiraterone N-oxide sulfate, and 100
      10,000 ng/mL for abiraterone sulfate. Intra-assay and interassay variabilities
      were within +/-15% of the nominal concentrations for quality control samples at
      medium and high concentrations and within +/-20% at the lower limit of
      quantification, respectively. CONCLUSIONS: The described method for simultaneous
      determination of abiraterone and enzalutamide was validated successfully and
      provides a useful tool for therapeutic drug monitoring in patients treated with
      these agents.

PMID- 28490046
TI  - Rapid Homogeneous Immunoassay to Quantify Gemcitabine in Plasma for Therapeutic
      Drug Monitoring.
AB  - BACKGROUND: Gemcitabine (2',2'-difluoro-2'-deoxycytidine) is a nucleoside analog
      used as a single agent and in combination regimens for the treatment of a variety
      of solid tumors. Several studies have shown a relationship between gemcitabine
      peak plasma concentration (Cmax) and hematological toxicity. An immunoassay for
      gemcitabine in plasma was developed and validated to facilitate therapeutic drug
      monitoring (TDM) by providing an economical, robust method for automated
      chemistry analyzers. METHODS: A monoclonal antibody was coated on nanoparticles
      to develop a homogenous agglutination inhibition assay. To prevent ex vivo
      degradation of gemcitabine in blood, tetrahydrouridine was used as a sample
      stabilizer. Validation was conducted for precision, recovery, cross-reactivity,
      and linearity on a Beckman Coulter AU480. Verification was performed on an AU5800
      in a hospital laboratory. A method comparison was performed with (LC-MS/MS)
      liquid chromatography tandem mass spectrometry using clinical samples.
      Selectivity was demonstrated by testing cross-reactivity of the major metabolite,
      2',2'-difluorodeoxyuridine. RESULTS: Coefficients of variation for repeatability
      and within-laboratory precision were <8%. The deviation between measured and
      assigned values was <3%. Linear range was from 0.40 to 33.02 MU/mL (1.5-125.5
      MUM). Correlation with validated LC-MS/MS methods was R = 0.977. The assay was
      specific for gemcitabine: there was no cross-reactivity to 2',2'
      difluorodeoxyuridine, chemotherapeutics, concomitant, or common medications
      tested. Tetrahydrouridine was packaged in single-use syringes. Gemcitabine
      stability in whole blood was extended to 8 hours (at room temperature) and in
      plasma to 8 days (2-8 degrees C). CONCLUSIONS: The assay demonstrated the
      selectivity, test range, precision, and linearity to perform reliable
      measurements of gemcitabine in plasma. The addition of stabilizer improved the
      sample handling. Using general clinical chemistry analyzers, gemcitabine could be
      measured for TDM.

PMID- 28490048
TI  - Simultaneous Determination of Imatinib, Dasatinib, and Nilotinib by Liquid
      Chromatography-Tandem Mass Spectrometry and Its Application to Therapeutic Drug
      Monitoring.
AB  - BACKGROUND: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors
      (TKIs) used as first-line treatment of chronic myeloid leukemia. Therapeutic drug
      monitoring is important to achieve treatment efficacy in the case of imatinib and
      nilotinib, and to control toxicity in the case of dasatinib. New high-sensitivity
      methods to monitor those drugs are needed, especially for dasatinib. Thus, a
      simple method to determine plasma levels of imatinib, dasatinib, and nilotinib
      for application in clinical practice was developed. METHODS: TKIs were eluted
      with a Poroshell 120 EC-C18 column (2.1 * 75 mm, 2.7 MUm) at 0.5 mL/min and 60
      degrees C, under gradient conditions through a mobile phase consisting of 4
      mmol/L ammonium formate, pH 3.2 (65%), and acetonitrile (35%). TKIs were detected
      and quantified by liquid chromatography in tandem with mass spectrometry (LC/MS
      MS) with positive electrospray ionization and analytes were extracted using solid
      phase extraction (Versaplate-SCX). Internal standards were isotope-labeled for
      each analyte. RESULTS: The method was linear in the range of 2.5-5000 ng/mL for
      imatinib, 0.75-400 ng/mL for dasatinib, and 2-4000 ng/mL for nilotinib. The
      validation assays for accuracy and precision, matrix effect, extraction recovery,
      carryover, and stability of the samples for all the TKIs were appropriate
      according to regulatory agencies. Furthermore, imatinib plasma samples, stored
      for 4 years at -80 degrees C were quite stable in approximately half of the
      samples. CONCLUSIONS: The method enables rapid quantification of TKI
      concentrations and is being applied to therapeutic drug monitoring to adjust dose
      and to manage adverse reactions in clinical practice.

PMID- 28490050
TI  - Is Trough Concentration of Vancomycin Predictive of the Area Under the Curve? A
      Commentary.

PMID- 28490049
TI  - Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations.
AB  - BACKGROUND: Previous findings revealed high correlations between serum/plasma and
      saliva levetiracetam concentrations, indicating saliva as an alternative matrix
      for monitoring levetiracetam therapy. Levetiracetam concentration in the hair,
      which could reflect long-term drug exposure and patients' compliance, has not
      been systematically tested, as yet. The aim of this study was to determine the
      correlation between plasma, saliva, and hair levetiracetam concentrations in 47
      patients with epilepsy. METHODS: Plasma, saliva, and hair levetiracetam
      concentrations were measured by liquid chromatography-tandem mass spectrometry
      with positive ionization. RESULTS: Levetiracetam saliva and plasma concentrations
      were highly correlated (r = 0.93). Plasma concentrations were not influenced by
      sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair
      concentrations correlated with plasma concentrations (r = 0.36) but not daily
      dose (mg/kg). Drug hair concentrations were not influenced by hair color or
      treatment (dyed). CONCLUSIONS: The results tend to indicate that saliva may be a
      reliable alternative to plasma for monitoring levetiracetam concentrations.
      Levetiracetam can also be detected in human hair.

PMID- 28490051
TI  - Comparison of flavour qualities of mushrooms (Flammulina velutipes) packed with
      different packaging materials.
AB  - To clarify the dynamic changes of flavour components in mushrooms packed with
      different packaging materials during storage, comprehensive flavour
      characterization, non-volatile and volatile compounds of Flammulina velutipes
      were evaluated using electronic nose (E-nose), electronic tongue (E-tongue)
      technology and headspace solid phase micro-extraction combined with gas
      chromatography-mass spectrometry (HS-SPME-GC-MS), respectively. Results showed
      that volatile compounds of fresh F. velutipes mainly consisted of ketones and
      alcohols, with 3-octanone being the predominant compound. After storage, volatile
      components significantly changed in mushrooms packed with normal packaging
      material (Normal-PM) according to the GC-MS analysis and radar fingerprint chart
      of electronic nose. The ethanol accumulation was inhibited by nanocomposite
      packaging materials (Nano-PM). Besides, both radar graph and PCA of E-tongue
      signals could differentiate the samples from different packaging and storage
      time. In general, these results may provide a profile of flavour substances and
      explain mechanism of flavour changes in F. velutipes over storage period.

PMID- 28490052
TI  - Effects of endogenous cysteine proteinases on structures of collagen fibres from
      dermis of sea cucumber (Stichopus japonicus).
AB  - Autolysis of sea cucumber, caused by endogenous enzymes, leads to postharvest
      quality deterioration of sea cucumber. However, the effects of endogenous
      proteinases on structures of collagen fibres, the major biologically relevant
      substrates in the body wall of sea cucumber, are less clear. Collagen fibres were
      prepared from the dermis of sea cucumber (Stichopus japonicus), and the
      structural consequences of degradation of the collagen fibres caused by
      endogenous cysteine proteinases (ECP) from Stichopus japonicus were examined.
      Scanning electron microscopic images showed that ECP caused partial
      disaggregation of collagen fibres into collagen fibrils by disrupting
      interfibrillar proteoglycan bridges. Differential scanning calorimetry and
      Fourier transform infrared analysis revealed increased structural disorder of
      fibrillar collagen caused by ECP. SDS-PAGE and chemical analysis indicated that
      ECP can liberate glycosaminoglycan, hydroxyproline and collagen fragments from
      collagen fibres. Thus ECP can cause disintegration of collagen fibres by
      degrading interfibrillar proteoglycan bridges.

PMID- 28490053
TI  - Prebiotic effect of xylooligosaccharides produced from birchwood xylan by a novel
      fungal GH11 xylanase.
AB  - A fungal endoxylanase belonging to the glycoside hydrolase gene family 11 (GH11)
      was obtained from the ascomycete Talaromyces amestolkiae. The enzyme was
      purified, characterized and used to produce a mixture of xylooligosaccharides
      (XOS) from birchwood xylan. A notable yield of neutral XOS was obtained (28.8%)
      upon enzyme treatment and the mixture contained a negligible amount of xylose,
      having xylobiose, xylotriose and xylotetraose as its main components. The
      prebiotic potential of this mixture was demonstrated upon analyzing the
      variations in microorganisms' composition and organic acids profile in breast-fed
      child faeces fermentations. The strong production of acetic and lactic acid, the
      decrease of potentially pathogenic bacteria and the increase of bifidobacteria,
      and possible beneficial commensals, confirmed the prebiotic value of these
      xylooligosaccharides.

PMID- 28490054
TI  - Evaluation of processing effects on anthocyanin content and colour modifications
      of blueberry (Vaccinium spp.) extracts: Comparison between HPLC-DAD and CIELAB
      analyses.
AB  - Colour is the first organoleptic property that consumers appreciate of a
      foodstuff. In blueberry (Vaccinium spp.) fruits, the anthocyanins are the
      principal pigments determining the colour as well as many of the beneficial
      effects attributed to this functional food. Commercial blueberry-derived products
      represent important sources of these healthy molecules all year round. In this
      study, blueberries were produced into purees comparing two homogenization methods
      and further heated following different thermal treatments. All the supernatants
      of the homogenates were monitored for pH. Then, the hydroalcoholic extracts of
      the same samples were characterized by CIELAB and HPLC-DAD analyses. These
      analytical techniques provide complementary information on fruit pigments content
      as a whole and on quali-quantitative profile of the single bioactive colorants.
      These data could be very interesting to know the best manufacturing procedure to
      prepare blueberry-derived products, well accepted by the consumers, while
      maintaining their healthy properties unaltered.

PMID- 28490055
TI  - Carotenoid bioaccessibility and the relation to lipid digestion: A kinetic study.
AB  - The micellar incorporation of carotenoids (lycopene, alpha- and beta-carotene)
      and lipid digestion products (free fatty acids, FFAs, and monoacylglycerides,
      MAGs) during in vitro digestion of oil-in-water emulsions was investigated by a
      kinetic approach. A fractional conversion model could adequately describe the
      hydrolysis of triacylglycerides, formation of FFAs and MAGs, and micellar
      incorporation of carotenoids, FFAs and MAGs. The release of FFAs and MAGs from
      TAGs proceeded faster than their incorporation into micelles. Rate constants of
      carotenoid micellar incorporation were inversely proportional to their
      hydrophobicity and dependent on the isomeric configuration, being the
      incorporation of the cis faster than their all-trans isomers. Furthermore, a
      positive linear relation was found between the micellar incorporation of
      carotenoids and lipid digestion products. The isomeric form of carotenoids did
      not affect such relation. The present kinetic approach can be useful to gain
      mechanistic insight into carotenoid bioaccessibility as affected by various
      process- and product-related factors.

PMID- 28490057
TI  - Surface molecularly imprinted polymer capped Mn-doped ZnS quantum dots as a
      phosphorescent nanosensor for detecting patulin in apple juice.
AB  - A Mn-doped ZnS quantum dots (QDs) based nanosensor for selective phosphorescent
      determination of patulin (PAT) was synthesized with 6-hydroxynicotinic acid (6
      HNA) as dummy template via a surface molecular imprinting sol-gel process. FTIR
      and XRD indicated the successful graft of molecularly imprinted polymer (MIP)
      onto crystal QDs. Binding tests revealed that the MIP-QDs presented higher
      selectivity, adsorption capacity and mass transfer rate than non-imprinted
      polymers, demonstrating a specific recognition for PAT among competitive
      mycotoxins and its analogues with the imprinting factor of 2.02. The MIP-QDs
      could recognize PAT in a linear range of 0.43-6.50MUmolL-1 with a detection limit
      of 0.32MUmolL-1 and a correlation coefficient (R2) of 0.9945. Recoveries of 102.9
      127.2% with relative standard deviations <4.95% were achieved in apple juice
      samples which were in good agreement with high-performance liquid chromatography
      (HPLC) (P>0.05). The results indicated a simple phosphorescent nanosensor for PAT
      detection in complex matrix.

PMID- 28490056
TI  - Roles of different initial Maillard intermediates and pathways in meat flavor
      formation for cysteine-xylose-glycine model reaction systems.
AB  - To explore initial Maillard reaction pathways and mechanisms for maximal
      formation of meaty flavors in heated cysteine-xylose-glycine systems, model
      reactions with synthesized initial Maillard intermediates, Gly-Amadori, TTCA (2
      threityl-thiazolidine-4-carboxylic acids) and Cys-Amadori, were investigated.
      Relative relativities were characterized by spectrophotometrically monitoring the
      development of colorless degradation intermediates and browning reaction
      products. Aroma compounds formed were determined by solid-phase microextraction
      combined with GC-MS and GC-olfactometry. Gly-Amadori showed the fastest reaction
      followed by Cys-Amadori then TTCA. Free glycine accelerated reaction of TTCA,
      whereas cysteine inhibited that of Gly-Amadori due to association forming
      relatively stable thiazolidines. Cys-Amadori/Gly had the highest reactivity in
      development of both meaty flavors and brown products. TTCA/Gly favored yielding
      meaty flavors, whereas Gly-Amadori/Cys favored generation of brown products.
      Conclusively, initial formation of TTCA and pathway involving TTCA with glycine
      were more applicable to efficiently produce processed-meat flavorings in a
      cysteine-xylose-glycine system.

PMID- 28490058
TI  - A cold active transglutaminase from Antarctic krill (Euphausia superba):
      Purification, characterization and application in the modification of cold-set
      gelatin gel.
AB  - Transglutaminase (TGase), EC 2.3.2.13, was purified from whole Antarctic krill
      (Euphausia superba) using ammonium sulfate fractionation and DEAE-Sephacel
      chromatography. The purified enzyme had specific activity, purification fold and
      yield of 53.518U/mg, 10.272 and 10.992%, respectively. The molecular weight of
      the purified Antarctic krill TGase was estimated to be 78kDa using sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal pH and
      temperature for the activity of the purified TGase were pH 8.0-9.0 and 0-10
      degrees C, respectively. However, the TGase activity reduced to 50% at a higher
      temperature of 45 degrees C. The cations Ca++ and Na+ activated the purified
      TGase activity optimally at levels of incorporation of 10mM and 1.8mM,
      respectively. Addition of TGase at 0.1U/mg increased the gel strength (p<0.05),
      setting temperature, setting time (p<0.05) and melting temperature (p<0.05) of
      cold-set gelatin gel.

PMID- 28490059
TI  - Lipid classes and fatty acids composition of the roe of wild Silurus glanis from
      subalpine freshwater.
AB  - The fat content and the fatty acid composition of the roe of European catfish
      (Silurus glanis) wild specimens captured in the Lambro river basin (Como,
      Northern Italy) were investigated in order to assess their nutritional value.
      Total extracted lipid values on roe weight were 5.8-6.3%. Phospholipids (40.2
      43.6%) and triacylglycerols (31.8-34.7%) were the most represented lipid classes.
      Relevant amount of cholesteryl esters (14.3-15.6%) were also detected. The main
      fatty acids were palmitic, oleic and cis-4,7,10,13,16,19-docosahexaenoic acid
      (DHA). Total saturated fatty acids were 28.1-30.9%, monounsaturated fatty acids
      were 28.2-30.6%, and polyunsaturated fatty acids (PUFAs) were 26.7-29.1%. The
      good found content of phospholipids and omega3-polyunsaturated fatty acids
      encourage further investigation for the exploitation of Silurus glanis roe in
      food products and/or supplements.

PMID- 28490060
TI  - Determination of flubendiamide in honey at trace levels by using solid phase
      extraction and liquid chromatography coupled to quadrupole time-of-flight mass
      spectrometry.
AB  - In this study, a new method has been developed to determine flubendiamide in
      honey using liquid chromatography coupled to a selective mass spectrometry
      detector (quadrupole-time-of-flight). An efficient sample treatment involving a
      solid phase extraction with a C18 sorbent was proposed (average analyte
      recoveries were between 94 and 104%). Chromatographic analysis (9min) was
      performed on a C18 column (Gemini C18, 50*2.0mm, 3um, 110A). The mobile phase
      consisted of water and acetonitrile, with a flow rate of 0.5mL/min in gradient
      elution mode. The method was fully validated in terms of selectivity, limits of
      detection and quantification, matrix effect, linearity, trueness and precision.
      Low limits of detection and quantification were obtained, ranging from 0.1 to
      0.2ug/kg and 0.4 to 0.6ug/kg, respectively. The method was applied to analyze
      flubendiamide in honey from different botanic origins (multifloral, rosemary and
      heather).

PMID- 28490061
TI  - The inclusion complex of oxyresveratrol in modified cyclodextrins: A
      thermodynamic, structural, physicochemical, fluorescent and computational study.
AB  - The interaction between oxyresveratrol (a type of stilbene with high biological
      activity) and modified cyclodextrins (CDs) was studied. Using HPLC-RP, was seen
      to form a 1:1 complex with all the CDs tested. The best CD in this respect was
      MbetaCD (KF=606.65+/-30.18M-1), the complexation showing a strong dependence on
      pH and temperature: The complexation constant (KF) decreased as the pH and
      temperature increased. The thermodynamic parameters studied (DeltaH degrees ,
      DeltaS degrees  and DeltaG degrees ) showed negative entropy, enthalpy and Gibbs
      free energy change at 25 degrees C. In addition, fluorescence signal of
      oxyresveratrol increased when MbetaCD was added. The oxyresveratrol emission and
      excitation spectra were obtained for first time. A 1H NMR was carried out to
      study the structure of the complex and, DSC studied demonstrated the
      complexation. A computational study by molecular docking was made to complement
      the structural study.

PMID- 28490062
TI  - Impact of frozen storage time on the volatile profile of wheat bread crumb.
AB  - The freezing of wheat bread before aroma analyses is a common practice in order
      to preserve loss of the volatile profile. However, the impact of the frozen
      storage time on the aroma profile has not been studied. For this purpose, the
      volatile profiles of wheat bread frozen for 1, 2 and 4weeks were analysed
      employing solvent extraction and static headspace methoologies with GC/MS. The
      results revealed that the freezing was effective to prevent the loss of volatiles
      during the first week. However, after two weeks, there was an increase of
      volatile compounds, probably generated by chemical reactions. Thus, a maximum of
      one week of frozen storage was recommended when using the solvent extraction
      methodology. When using the static headspace method, the samples should be
      analysed on the same day as preparation, since the extraction was surprisingly
      increased due to the starch retrogradation that occurred during freezing.

PMID- 28490063
TI  - Characterisation of a thiamine diphosphate-dependent alpha-keto acid
      decarboxylase from Proteus mirabilis JN458.
AB  - Alpha-keto acid decarboxylases can convert keto acids to their corresponding
      aldehydes, which are often volatile aroma compounds. The gene encoding alpha-keto
      acid decarboxylase in Proteus mirabilis JN458 was cloned, and the enzyme
      overexpressed in Escherichia coli BL21 (DE3), purified in high yield, and
      characterised. The molecular weight is 62.291kDa by MALDI-TOF MS, and optimum
      activity at pH 6.0 and 40-50 degrees C. The enzyme is a typical decarboxylase,
      dependent on thiamine diphosphate and Mg2+ as cofactors. For the decarboxylation
      reaction, the enzyme displayed a broad substrate range. Kinetic parameters were
      determined using 4-methyl-2-oxopentanoic acid, phenyl pyruvate and 3-methyl-2
      oxopentanoic acid as substrates. Km and kcat values for phenyl pyruvate were
      0.62mM and 77.38s-1, respectively, and the kcat/Km value was 124.81mM-1s-1. The
      enzyme properties suggest it may act effectively under cheese ripening
      conditions.

PMID- 28490064
TI  - Thymol nanoemulsions formed via spontaneous emulsification: Physical and
      antimicrobial properties.
AB  - In this work, we prepared various sub-micron thymol emulsions with high
      hydrophilic-lipophilic balance (HLB) surfactants via spontaneous emulsification.
      Emulsion properties, such as size, polydispersity and charge, were assessed for
      each surfactant type and mass fraction. Emulsion stability was characterized by
      monitoring droplet size following exposure to physical (centrifugation) and
      thermal stressors (freeze, thaw cycling). Emulsions were subsequently screened
      against several challenge pathogens to evaluate antimicrobial efficacy. Based on
      these time-kill assays, exemplary formulations were further tested as sanitizing
      washes on lettuce and blueberries inoculated with food-borne bacterial biofilms.
      Antimicrobial data elucidate both surfactant and formulation specific antagonisms
      between thymol and the emulsifying agents. However, the best emulsion
      compositions were capable of reducing planktonic bacteria by >4 logs and biofilm
      bacteria by 1.5-2.5 logs in 60 s. These results are comparable to the efficacy of
      chlorine at ~50-200ppm. The experimental results have implications in emulsion
      formulations involving thymol and other terpenoids.

PMID- 28490065
TI  - Residue analysis of tetracyclines in milk by HPLC coupled with hollow fiber
      membranes-based dynamic liquid-liquid micro-extraction.
AB  - A novel hollow fiber membranes-based dynamic liquid-liquid micro-extraction (HF
      DLLME) coupled with HPLC-UV detection has been developed for the residue analysis
      of tetracyclines in milk samples without deproteinization and degreasing. The
      influences of experimental parameters were investigated and optimized. The method
      showed a good performance. The limits of detection (LOD) are in the range of 0.95
      3.6MUg/L. The recoveries in spiked samples range from 92.38 to 107.3%. The
      relative standard deviations (RSDs) are lower than 8.66%. The advantages of this
      method are simple operation, high efficiency, absence of sample carryover and low
      cost.

PMID- 28490066
TI  - The physico-chemical alteration of lovastatin and enhanced antioxidant effect of
      Bacillus subtilis fermented-red yeast rice product.
AB  - Red yeast rice product (RYP) has been used as a food supplement because of its
      lipid lowering, and in food additives as a natural colorant. Lovastatin of RYP is
      a hypolipidemic commercial drug. To enhance the beneficial effects of RYP, we
      performed a bioconversion with Bacillus subtilis. This B. subtilis-fermentation
      process of RYP increased the ratio of the active open-hydroxyl acid form and the
      prodrug lactone form of lovastatin, which is a potent cholesterol synthesis
      inhibitor. 3(2H)-benzofuranone was newly produced in the fermented red yeast rice
      product (FRYP) as analyzed by GC-MS. FRYP increased the free radical scavenging
      activity compared with RYP. FRYP blocked xanthine oxidase (XO)-induced oxidative
      cytotoxicity and inhibited the H2O2-induced intracellular ROS in cells. This is
      the first study to illustrate that B. subtilis-fermented FRYP is useful for
      facilitating the alteration in the physico-chemical property of lovastatin and
      enhancing antioxidant activity, which may have greater pharmacological activity.

PMID- 28490067
TI  - Comparison of nutritional quality and sensory acceptability of biscuits obtained
      from native, fermented, and malted pearl millet (Pennisetum glaucum) flour.
AB  - The effects of fermentation and malting on the proximate composition, mineral
      content, amino acids and total phenolic content of pearl millet flour and
      biscuits were studied. Consumer tests of the biscuits samples were also done
      using two sets of panelists. The results showed that fermentation and malting
      improved the crude fiber, crude protein, carbohydrate and energy values of the
      pearl millet flour. For the biscuit samples, the fermented and malted biscuits
      had higher moisture, crude protein, crude fiber and energy value with lower fat
      and ash content as compared to the biscuits obtained from native flour.
      Fermentation and malting were further observed to increase majority of the
      essential and non-essential amino acids. Consumer tests among the different set
      of panelists showed differences in the loading patterns as observed through
      principal component analysis. In conclusion, this study shows that fermentation
      and malting improves nutritional, health composition of pearl millet flour as
      well as the sensorial acceptability of subsequent biscuits.

PMID- 28490068
TI  - Micropollutants and chemical residues in organic and conventional meat.
AB  - The chemical contamination levels of both conventional and organic meats were
      assessed. The objective was to provide occurrence data in a context of chronic
      exposure. Environmental contaminants (17 polychlorinated
      dibenzodioxins/dibenzofurans, 18 polychlorinated biphenyls (PCBs), 3
      hexabromocyclododecane (HBCD) isomers, 6 mycotoxins, 6 inorganic compounds)
      together with chemical residues arising from production inputs (75
      antimicrobials, 10 coccidiostats and 121 pesticides) have been selected as
      relevant compounds. A dedicated sampling strategy, representative of the French
      production allowed quantification of a large sample set (n=266) including both
      conventional (n=139) and organic (n=127) raw meat from three animal species
      (bovine, porcine, poultry). While contamination levels below regulatory limits
      were measured in all the samples, significant differences were observed between
      both species and types of farming. Several environmental contaminants (Dioxins,
      PCBs, HBCD, Zn, Cu, Cd, Pb, As) were measured at significantly higher levels in
      organic samples.

PMID- 28490069
TI  - Study of the contribution of massoia lactone to the aroma of Merlot and Cabernet
      Sauvignon musts and wines.
AB  - Organic extracts of musts and red wines marked by dried fruit and cooked fruit
      aromas were analyzed by gas chromatography coupled to olfactometry and mass
      spectrometry. Thanks to this analytical approach we identified a fragrant lactone
      corresponding to an odorant zone reminiscent of coconut and dried figs as 5,6
      dihydro-6-pentyl-2H-pyran-2-one (C10 massoia lactone). Using chiral GC-GC-MS, we
      show that only the (R)-C10 massoia lactone is found in musts and wines. Its
      detection thresholds were 10ug/L and 11ug/L in must and wine model solution,
      respectively. In Merlot and Cabernet Sauvignon musts marked by dried fruit
      flavors from overripe grapes, its concentration reached 68ug/L. In contrast, in
      wines marked by these flavors, it never exceeded 20ug/L. We show that (R)-C10
      massoia lactone is reduced to (R)-delta-decalactone during alcoholic
      fermentation. In addition, we underline the contribution of temperature during
      the growing season on its level in old red wines.

PMID- 28490070
TI  - Utilisation of immature wheat flour as an alternative flour with antioxidant
      activity and consumer perception on its baked product.
AB  - The purpose of this study was to investigate the utilisation of immature wheat
      flour (IWF) as an alternative flour with antioxidant activity. Antioxidant
      properties and phenolic acid compositions of IWF and IWF madeleine were compared
      with those of commercial wheat flour (WF) and WF madeleine. Consumer perception
      of madeleine was studied using a blind test followed by an informed test, which
      provided information on antioxidant properties of flours. The bound ferulic acid
      in IWF (5.54mg/100g) was seven times higher than that in WF (0.74mg/100g). Oxygen
      radical absorbance capacity of IWF (34.47umol TE/g) and IWF madeleine (14.63umol
      TE/g) were higher than those of WF. The results of blind test showed that
      consumer acceptability and willingness to pay (WTP) of IWF madeleine were lower
      than those of WF madeleine. However, about 25% of consumers preferred IWF
      madeleine, implying small niche market for IWF as alternative flour.

PMID- 28490071
TI  - Recovery of a bacteriocin-like inhibitory substance from Pediococcus acidilactici
      Kp10 using surfactant precipitation.
AB  - Bacteriocin is an important peptide which can be used as an anti-microbial agent
      in food. However, simpler and more cost-effective purification methods need to be
      developed compared to chromatography to enhance its commercial viability.
      Surfactant precipitation was employed for the first time to purify bacteriocin
      like inhibitory substance (BLIS) from a fermentation broth of Pediococcus
      acidilactici Kp10, and the amount precipitated was investigated as a function of
      anionic surfactant (AOT) concentration, and pH. Protein recovery from the
      precipitate was accomplished using solvent extraction, and solvent type, NaCl
      concentration, and ionic strength of the final solution were optimised. Optimal
      conditions were; 1.05mM of AOT at pH 4 for precipitation, and acetone extraction
      (with 1mM NaCl), which resulted in an 86.3% yield, and 53.8 purification factor.
      This study highlighted the fact that surfactant precipitation can be used as a
      primary recovery method for BLIS from a complex fermentation broth.

PMID- 28490072
TI  - Evolution of free and bound volatile aroma compounds and phenols during
      fermentation of Muscat blanc grape juice with and without skins.
AB  - Recently, various technologies which utilise fermentation with skins have been
      developed for obtaining distinct white wines. This study first reports the
      dynamic changes of volatiles and phenols that occur during skin fermentation in
      white winemaking. Volatiles were analysed by solid-phase extraction (SPE), solid
      phase microextraction (SPME) and gas chromatography (GC), and phenols by ultra
      performance liquid chromatography (UPLC), both with mass spectrometric detection.
      Monoterpenols increased during the first 3days of skin fermentation, after which
      certain glycosides decreased, but were higher than in control. The presence of
      skins reduced ho-trienol, beta-damascenone, acids and esters. After a 1-3days lag
      phase, skin fermentation caused a constant increase of most phenols. It was
      estimated that skin fermentation up to 1-3days might be beneficial for
      monoterpenol varietal aroma, which should be re-evaluated through further
      studies. Longer durations promoted phenol extraction more strongly, which is
      possibly suitable for obtaining more distinct wines or blending components.

PMID- 28490073
TI  - The use of high hydrostatic pressure to generate folate-enriched extracts from
      the granule fraction of hen's egg yolk.
AB  - The present work characterized the effects of pre-treatments on the protein
      profile and microstructure of granule fractions from egg yolk. The granule
      microstructure was studied using confocal laser scanning microscopy (CLSM). The
      protein profiles of the pre-treated granule and the corresponding plasma fraction
      were studied using 2D gel electrophoresis techniques. Further, we explored the
      potential for using high hydrostatic pressure (HHP) to promote disintegration of
      the granule structure. The CLSM micrographs provided evidence of the substantial
      disintegration of granules due to HHP (600MPa/5min). Results from high
      performance liquid chromatography (HPLC) analysis indicated high concentrations
      of folate in the plasma fractions (230ug/g dry matter) separated from the HHP
      treated granule. Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS
      PAGE) analysis revealed the localization of phosvitin in the plasma fraction,
      which correlated with higher folate concentrations. The results demonstrate that
      phosvitin and folate were stable under the HHP conditions applied in this study.
      These findings provide evidence of a putative interaction between phosvitin and
      folate, and offer an improved model for the structure of granule.

PMID- 28490074
TI  - Determination of heat-set gelation capacity of a quinoa protein isolate
      (Chenopodium quinoa) by dynamic oscillatory rheological analysis.
AB  - This work aimed to study the influence of pH (3.5 and 7.0) and CaCl2 and MgCl2
      addition on heat-set gelation of a quinoa protein isolate at 10% and 15% (w/w).
      The protein isolate obtained was composed mainly of 11S globulin as was observed
      by electrophoresis and mass spectrometry analysis. Heat-set gelation occurred at
      both pH values studied. Nevertheless, the gels formed at pH 3.5 were more
      viscoelastic and denser than those formed at pH 7.0, that was coarser and
      presented syneresis. The CaCl2 and MgCl2 addition increased the gel strength
      during rheological analysis at pH 3.5, possibly due to the formation of fiber
      like connections in the gel network. At pH 7.0, the divalent salts resulted in
      weaker gels formed by agglomerates, suggesting a neutralization of the protein
      surface charges. The differences in quinoa protein gelation were attributed to
      solubility, and the flexibility of proteins secondary structure at the pH
      studied.

PMID- 28490075
TI  - Development of a near-infrared spectroscopy method (NIRS) for fast analysis of
      total, indolic, aliphatic and individual glucosinolates in new bred open
      pollinating genotypes of broccoli (Brassica oleracea convar. botrytis var.
      italica).
AB  - This study describes the development of near-infrared spectroscopy (NIRS)
      calibration to determine individual and total glucosinolates (GSLs) content of 12
      new-bred open-pollinating genotypes of broccoli (Brassica oleracea convar.
      botrytis var. italica). Six individual GSLs were identified using high
      performance-liquid chromatography (HPLC). The NIRS calibration was established
      based on modified partial least squares regression with reference values of HPLC.
      The calibration was analyzed using coefficient of determination in prediction
      (R2) and ratio of preference of determination (RPD). Large variation occurred in
      the calibrations, R2 and RPD due to the variability of the samples. Derived
      calibrations for total-GSLs, aliphatic-GSLs, glucoraphanin and 4
      methoxyglucobrassicin were quantitative with a high accuracy (RPD=1.36, 1.65,
      1.63, 1.11) while, for indole-GSLs, glucosinigrin, glucoiberin, glucobrassicin
      and 1-methoxyglucobrassicin were more qualitative (RPD=0.95, 0.62, 0.67, 0.81,
      0.56). Overall, the results indicated NIRS has a good potential to determine
      different GSLs in a large sample pool of broccoli quantitatively and
      qualitatively.

PMID- 28490076
TI  - Lipase mediated synthesis of rutin fatty ester: Study of its process parameters
      and solvent polarity.
AB  - Lipophilization of antioxidants is recognized as an effective strategy to enhance
      solubility and thus effectiveness in lipid based food. In this study, an effort
      was made to optimize rutin fatty ester synthesis in two different solvent systems
      to understand the influence of reaction system hydrophobicity on the optimum
      conditions using immobilised Candida antartica lipase. Under unoptimized
      conditions, 52.14% and 13.02% conversion was achieved in acetone and tert-butanol
      solvent systems, respectively. Among all the process parameters, water activity
      of the system was found to show highest influence on the conversion in each
      reaction system. In the presence of molecular sieves, the ester production
      increased to 62.9% in tert-butanol system, unlike acetone system. Under optimal
      conditions, conversion increased to 60.74% and 65.73% in acetone and tert-butanol
      system, respectively. This study shows, maintaining optimal water activity is
      crucial in reaction systems having polar solvents compared to more non-polar
      solvents.

PMID- 28490077
TI  - Characterization of Satsuma mandarin (Citrus unshiu Marc.) nectar-to-honey
      transformation pathway using FTIR-ATR spectroscopy.
AB  - Samples of Satsuma mandarin (Citrus unshiu Marc.) nectar, honey sac content and
      honey were analyzed by FTIR-ATR spectroscopy and reference methods. The spectral
      analysis allowed detection of the major chemical constituents in C. unshiu nectar
      to-honey transformation pathway thus providing information on the intensity and
      location of the compositional changes occurring during this process. The
      preliminary results showed that in average more than one-third of sugar-related
      nectar-to-honey conversion takes place directly in the honey sac; the average
      sugar content (w/w) was 17.93% (nectar), 47.03% (honey sac) and 79.63% (honey).
      FTIR-ATR results showed great spectral similarity of analyzed honey samples and
      small degree variations in both sugar and water content in nectar samples. The
      spectral data revealed distinctive differences in the chemical composition of
      individual honey sac contents with the most intensive and complex absorption
      envelope in the spectral region between 1175 and 950cm-1 (glucose, fructose and
      sucrose absorption bands).

PMID- 28490078
TI  - Characterization of phenolic compounds in chia (Salvia hispanica L.) seeds, fiber
      flour and oil.
AB  - The consumption of chia seeds products has increased recently and it has been
      suggested that the inclusion of this functional food in a daily human diet could
      contribute to improve consumers' health. However, a better knowledge about the
      composition of these products is mandatory. In this work, the phenolic compounds
      from commercial samples of chia seed, fiber flour and oil were extracted using an
      ultrasound-assisted methodology and were separated and identified by high
      performance liquid chromatography coupled to a mass spectrometer. Methanol:water
      extracts were prepared and submitted to an acidic hydrolysis. Crude and
      hydrolyzed extracts were analyzed and phenolic compounds found were mainly
      caffeic acid and danshensu and its derivatives, such as rosmarinic and
      salvianolic acids. TPC was higher in the hydrolyzed extracts. These results
      supply new information about the main phenolic compounds presents in chia, which
      are important dietary sources of natural antioxidants for prevention of diseases
      caused by oxidative stress.

PMID- 28490079
TI  - Influence of osmotic dehydration pre-treatment and combined drying method on
      physico-chemical and sensory properties of pomegranate arils, cultivar Mollar de
      Elche.
AB  - "Mollar de Elche" is the most popular Spanish pomegranate cultivar (intense
      sweetness and easy-to-chew arils); however, arils have pale pink colour and flat
      sensory profile. "Mollar the Elche" arils first underwent an osmotic dehydration
      pre-treatment (OD) with concentrated juices: (i) chokeberry, (ii) apple, and/or
      (iii) pomegranate cultivar "Wonderful", to improve their antioxidant capacity,
      colour, and sensory profile complexity, and later the arils were dried by a
      combined method (convective pre-drying+vacuum microwave finish drying). The use
      of OD provided dried arils with characteristic sweetness, and improved colour and
      aromatic complexity. The recommended OD methods were those using (i) pomegranate,
      and (ii) pomegranate with chokeberry juices; they improved the total anthocyanin
      content (mean of 368mgkg-1), red colour (a* coordinate 15.6), and antioxidant
      capacity (e.g. ABTS mean of 5.7mmolTrolox100g-1). However, further research is
      still needed because freeze-dried arils had the highest anthocyanin content.

PMID- 28490080
TI  - Utilization of watermelon pulp for lycopene extraction by response surface
      methodology.
AB  - Lycopene extraction was optimized from watermelon pulp using response surface
      methodology using independent variables:solvent/meal ratio (4:1-12:1v/w), number
      of extractions (1-5), temperature (20-60 degrees C) and extraction time (4
      20min). Watermelon pulp had 59.95mglycopene/100g on fresh weight basis. The
      experimental values of lycopene with selected combinations of independent
      variables were 8.20-59.17mg/100g on fresh weight basis. The second order model
      obtained revealed a coefficient of determination (R2) of 0.986, the standard
      error of 0.04, the root mean square error of 0.02 and a scattered plot between
      experimental and predicted values. The optimum solvent/meal ratio, number of
      extractions, temperature and extraction time were 10:1v/w, four, 50 degrees C and
      16min respectively. The optimum conditions of lycopene extraction were confirmed
      experimentally.

PMID- 28490081
TI  - Qualitative and quantitative analysis of milk for the detection of adulteration
      by Laser Induced Breakdown Spectroscopy (LIBS).
AB  - The present work focuses on the development of a fast and cost effective method
      based on Laser Induced Breakdown Spectroscopy (LIBS) to the quality control,
      traceability and detection of adulteration in milk. Two adulteration cases have
      been studied; a qualitative analysis for the discrimination between different
      milk blends and quantification of melamine in adulterated toddler milk powder.
      Principal Component Analysis (PCA) and neural networks (NN) have been used to
      analyze LIBS spectra obtaining a correct classification rate of 98% with a 100%
      of robustness. For the quantification of melamine, two methodologies have been
      developed; univariate analysis using CN emission band and multivariate
      calibration NN model obtaining correlation coefficient (R2) values of 0.982 and
      0.999 respectively. The results of the use of LIBS technique coupled with
      chemometric analysis are discussed in terms of its potential use in the food
      industry to perform the quality control of this dairy product.

PMID- 28490082
TI  - Spasmolytic, antimicrobial and cytotoxic activities of 5-phenylpentyl
      isothiocyanate, a new glucosinolate autolysis product from horseradish (Armoracia
      rusticana P. Gaertn., B. Mey. & Scherb., Brassicaceae).
AB  - Detailed analyses of horseradish autolysates led to the identification of a new
      natural product, 5-phenylpentyl isothiocyanate (PhPeITC). The structural
      assignment was corroborated by synthesis, and the identity unequivocally
      established by spectral means. The occurrence of PhPeITC is the first direct
      proof of the existence of a 5-phenylpentyl glucosinolate in the aerial parts of
      this species as one of the possible "mustard oil" precursors. To verify its
      possible contribution to the horseradish functional food status, horseradish
      above- and underground autolysates, together with five omega-phenylalkyl
      isothiocyanates were tested for their spasmolytic, cytotoxic and antimicrobial
      activities. Specifically, the cytotoxic effect on Caco-2, HeLa (cancer) and MDCK
      (non-cancer) cell lines was established. Additionally, the five tested ITCs
      exerted significant spasmolytic activity (on rat distal colon), with PhPeITC
      being almost 100 times more potent than papaverine. A non-selective antimicrobial
      activity of all ITCs was revealed in the case of 6 bacterial and 2 fungal
      strains.

PMID- 28490083
TI  - Combining hydrothermal pretreatment with enzymes de-pectinates and exposes the
      innermost xyloglucan-rich hemicellulose layers of wine grape pomace.
AB  - Chardonnay grape pomace was treated with pressurized heat followed by enzymatic
      hydrolysis, with commercial or pure enzymes, in buffered conditions. The pomace
      was unfermented as commonly found for white winemaking wastes and treatments
      aimed to simulate biovalorization processing. Cell wall profiling techniques
      showed that the pretreatment led to depectination of the outer layers thereby
      exposing xylan polymers and increasing the extractability of arabinans,
      galactans, arabinogalactan proteins and mannans. This higher extractability is
      believed to be linked with partial degradation and opening-up of cell wall
      networks. Pectinase-rich enzyme preparations were presumably able to access the
      inner rhamnogalacturonan I dominant coating layers due to the hydrothermal
      pretreatment. Patterns of epitope abundance and the sequential release of cell
      wall polymers with specific combinations of enzymes led to a working model of the
      hitherto, poorly understood innermost xyloglucan-rich hemicellulose layers of
      unfermented grape pomace.

PMID- 28490084
TI  - An integrated strategy combining DNA walking and NGS to detect GMOs.
AB  - Recently, we developed a DNA walking system for the detection and
      characterization of a broad spectrum of GMOs in routine analysis of food/feed
      matrices. Here, we present a new version with improved throughput and sensitivity
      by coupling the DNA walking system to Pacific Bioscience(r) Next-generation
      sequencing technology. The performance of the new strategy was thoroughly
      assessed through several assays. First, we tested its detection and
      identification capability on grains with high or low GMO content. Second, the
      potential impacts of food processing were investigated using rice noodle samples.
      Finally, GMO mixtures and a real-life sample were analyzed to illustrate the
      applicability of the proposed strategy in routine GMO analysis. In all tested
      samples, the presence of multiple GMOs was unambiguously proven by the
      characterization of transgene flanking regions and the combinations of elements
      that are typical for transgene constructs.

PMID- 28490085
TI  - Cellulose nanomaterials emulsion coatings for controlling physiological activity,
      modifying surface morphology, and enhancing storability of postharvest bananas
      (Musa acuminate).
AB  - Cellulose nanomaterials (CNs)-incorporated emulsion coatings with improved
      moisture barrier, wettability and surface adhesion onto fruit surfaces were
      developed for controlling postharvest physiological activity and enhancing
      storability of bananas during ambient storage. Cellulose nanofiber (CNF)-based
      emulsion coating (CNFC: 0.3% CNF/1% oleic acid/1% sucrose ester fatty acid (w/w
      wet base)) had low contact angle, high spread coefficient onto banana surfaces,
      and lower surface tension (ST, 25.4mN/m) than the critical ST (35.2mN/m) of
      banana peels, and exhibited good wettability onto banana surfaces. CNFC coating
      delayed the ethylene biosynthesis pathway and reduced ethylene and CO2
      production, thus delaying fruit ripening. As the result, CNFC coating minimized
      chlorophyll degradation, weight loss, and firmness of bananas while ensuring the
      properly fruit ripening during 10d of ambient storage. This study demonstrated
      the effectiveness of CNF based emulsion coatings for improving the storability of
      postharvest bananas.

PMID- 28490086
TI  - Molecular protocol for authentication of snappers (Lutjanidae-Perciformes) based
      on multiplex PCR.
AB  - Fraud involving fish products is regularly reported and investigated using
      genetic methods. However, no such approach has been applied to snappers, despite
      the commercial relevance of these fish. This study proposes an authentication
      protocol with multiplex PCR for three species of snappers (Lutjanus purpureus, L.
      synagris, and Ocyurus chrysurus). The protocol yielded a distinct triple-banding
      pattern for L. purpureus, whereas L. synagris and O. chrysurus showed a double
      banding pattern of different sizes, thereby allowing differentiation of the three
      species. The protocol was validated using fillets labeled as snapper or "Pargo"
      in Brazil, previously identified using DNA sequencing, amongst which substitution
      with Rhomboplites aurorubens was detected. When subjected to the new protocol,
      banding characteristic of L. purpureus were detected whilst R. aurorubens
      generated only the control band. Our study provides a practical tool for
      investigating substitutions and might assist in quality control and increase food
      safety for consumers.

PMID- 28490087
TI  - Use of FT-IR, FT-Raman and thermal analysis to evaluate the gel formation of
      curdlan produced by Agrobacterium sp. IFO 13140 and determination of its
      rheological properties with food applicability.
AB  - Curdlan is a linear polysaccharide composed of glucose units joined by beta-(1,3)
      bonds that possesses unique gelation properties. This study aimed to characterize
      the structure and evaluate the gelling properties of curdlan produced by
      Agrobacterium sp. IFO 13140 and its gels, as well as apply it in food. FT-Raman
      analysis highlighted the structural changes that occurred during the formation of
      gels, with variations related to the hydrogen bonds and hydrophobic interactions,
      which occur with the formation of the low-set and high-set gels, respectively.
      Rheological analysis showed that the pre-gelled commercial curdlan and the
      curdlan produced by Agrobacterium sp. IFO 13140 differed in terms of gelation
      properties, which depends of the degree of polymerization of the polysaccharide,
      but when applied to pasta products, both improved the texture parameters. The
      curdlan gels were found to have great potential as gelling agents to improve
      texture, water retention capacity and stability of food products.

PMID- 28490088
TI  - Antioxidant activities of aqueous extract from Stevia rebaudiana stem waste to
      inhibit fish oil oxidation and identification of its phenolic compounds.
AB  - We investigated the potential for exploiting Stevia rebaudiana stem (SRS) waste
      as a source of edible plant-based antioxidants finding for the first time that
      the hot water extract of SRS had significantly higher antioxidant activity
      against fish oil oxidation than that of the leaf, despite SRS extract having
      lower total phenolic content, DPPH radical scavenging activity and ORAC values.
      To locate the major antioxidant ingredients, SRS extract was fractionated using
      liquid chromatography. Five phenolic compounds (primary antioxidant components in
      activity-containing fractions) were identified by NMR and HR-ESI-MS: vanillic
      acid 4-O-beta-d-glucopyranoside (1), protocatechuic acid (2), caffeic acid (3),
      chlorogenic acid (4) and cryptochlorogenic acid (5). Further analysis showed
      that, among compounds 2-5, protocatechuic acid had the highest capacity to
      inhibit peroxides formation, but exhibited the lowest antioxidant activities in
      DPPH and ORAC assays. These results indicate that SRS waste can be used as strong
      natural antioxidant materials in the food industry.

PMID- 28490089
TI  - Molecular structure, stability and cytotoxicity of natural green colorants
      produced from Centella asiatica L. leaves treated by steaming and metal
      complexations.
AB  - Stability of extracts from Centella asiatica L. leaves treated by steaming and
      metal-chlorophylls complexations against combined acid-heat was compared with
      that from untreated leaves and synthetic colorant. Formation of metal
      chlorophylls complexes was confirmed by FTIR spectroscopy. Molecular structure
      changes during stability test and cytotoxicity of the extracts against Vero cells
      were evaluated. Utilization of the extracts as colorant was also assessed in
      selected beverage ingredient and food. Copper-chlorophylls extracts exhibited
      similar green hue to those from untreated and steamed leaves, while zinc
      chlorophylls extracts exhibited yellow-green color. Metal-chlorophylls extracts
      possessed higher stability against combined acid-heat than those from untreated
      and steamed leaves. Use of metal-chlorophylls extracts in beverage ingredient led
      to increased hue value due to their structural rearrangement, which was confirmed
      by changes in Q band of VIS spectra. Cytotoxicity of zinc- and copper
      chlorophylls extracts was slightly different and higher than those of extracts
      from untreated/steamed leaves and synthetic colorant.

PMID- 28490090
TI  - Effects of pan cooking on micropollutants in meat.
AB  - This work presents the effects of pan cooking on PCBs, PCDD/Fs, pesticides and
      trace elements in meat from a risk assessment perspective. Three different
      realistic cooking intensities were studied. A GC*GC-TOF/MS method was set up for
      the multiresidue analysis of 189 PCBs, 17 PCDD/Fs and 16 pesticides whereas Cd,
      As, Pb and Hg were assayed by ICP-MS. In terms of quantity, average PCB losses
      after cooking were 18+/-5% for rare, 30+/-3% for medium, and 48+/-2% for well
      done meat. In contrast, average PCDD/F losses were not significant. For
      pesticides, no loss occurred for aldrin, lindane, DDE or DDD, whereas losses
      exceeding 80% were found for dieldrin, sulfotep or phorate. Losses close to the
      margin of error were observed for trace elements. These results are discussed in
      light of the physicochemical properties of the micropollutants as well as of
      water and fat losses into cooking juice.

PMID- 28490091
TI  - Physico-chemical characterization of dairy gel obtained by a proteolytic extract
      from Calotropis procera - A comparison with chymosin.
AB  - Chymosin is the major enzyme used in cheesemaking but latex enzymes are also
      used. The aim of this work was to characterize the composition and the structure
      of dairy gel obtained by an extract of Calotropis procera leaves in comparison
      with those obtained by chymosin. The biochemical and mineral compositions of the
      curds and the cheese yields obtained by using Calotropis procera extract or
      chymosin were relatively similar. Quantitative and qualitative evaluations of
      proteolysis after milk coagulation, determined by the non-protein nitrogen
      content and chromatography coupled to mass spectrometry, indicated that
      Calotropis procera extract was more proteolytic than chymosin and that kappa
      casein was proteolyzed. The main consequence of proteolysis by Calotropis procera
      extract or chymosin was the formation of a similar and regular network with the
      presence of aggregates of casein micelles. These results support that Calotropis
      procera extract can be used as effective coagulant in cheesemaking.

PMID- 28490092
TI  - The contribution of wine-derived monoterpene glycosides to retronasal odour
      during tasting.
AB  - This study investigated the sensory significance of monoterpene glycosides during
      tasting, by retronasal perception of odorant aglycones released in-mouth.
      Monoterpene glycosides were isolated from Gewurztraminer and Riesling juices and
      wines, chemically characterised and studied using sensory time-intensity
      methodology, together with a synthesised monoterpene glucoside. When assessed in
      model wine at five times wine-like concentration, Gewurztraminer glycosides and
      geranyl glucoside gave significant fruity flavour, although at wine-like
      concentrations, or in the presence of wine volatiles, the effect was not
      significant. Gewurztraminer glycosides, geranyl glucoside and guaiacyl glucoside
      were investigated using a sensory panel (n=39), revealing large inter-individual
      variability, with 77% of panellists responding to at least one glycoside. The
      study showed for the first time that grape-derived glycosides can contribute
      perceptible fruity flavour, providing a means of enhancing flavour in wines, and
      confirms the results of previous studies that the effect is highly variable
      across individuals.

PMID- 28490093
TI  - Effect of heat, pH, ultrasonication and ethanol on the denaturation of whey
      protein isolate using a newly developed approach in the analysis of difference-UV
      spectra.
AB  - A newly developed method of analysis of difference-UV spectra was successfully
      implemented in the study of the effect of heat, pH, ultrasonication and ethanol
      on the denaturation of whey protein isolate. It was found that whey proteins
      exhibit their highest stability against heat denaturation at pH 3.75. At very low
      pH values, i.e. 2.5, they exhibited considerable cold denaturation, while after
      heating at this pH value, the supplementary heat denaturation rate was lower
      compared to that at neutral pH. The highest heat denaturation rates were observed
      at pH values higher than neutral. High power sonication on whey proteins,
      previously heated at 90 degrees C for 30min, resulted in a rather small reduction
      of the fraction of the heat denatured protein aggregates. Finally, when ethanol
      was used as a cosolvent in the concentration range 20-50%, a sharp increase in
      the degree of denaturation, compared to the native protein solution, was
      observed.

PMID- 28490094
TI  - Development of monoclonal antibody-based ELISA for the quantification of orange
      allergen Cit s 2 in fresh and processed oranges.
AB  - The aim of this study was to develop a monoclonal antibody (mAb)-based enzyme
      linked immunosorbent assay (ELISA) for the quantification of a major allergen
      (Cit s 2) in fresh and processed oranges. Purified recombinant Cit s 2 (rCit s 2)
      small ubiquitin-like modifier (SUMO) was used for the production of mAbs. In the
      optimized ELISA, the recovery of rCit s 2 from Navel oranges or orange juice was
      107-132%, and the intra- and inter-assay coefficients of variation were 3.1-8.8%
      and 4.4-11%, respectively. The Cit s 2 content in fresh oranges was determined to
      be 1,800+/-430ng/g, while this content was much lower in the processed foods. The
      developed ELISA demonstrated high reproducibility, sensitivity, and accuracy, and
      this assay may help individuals with orange allergy by determining Cit s 2
      quantities in food products and controlling their Cit s 2 intake.

PMID- 28490095
TI  - A cold-induced phytosulfokine peptide is related to the improvement of loquat
      fruit chilling tolerance.
AB  - A novel peptidomics approach was used to discover cold-induced peptides in loquat
      fruit. Twenty unique peptides derived from 18 proproteins were identified, and
      they were involved in sugar signalling, protein metabolism and stress response.
      The quantitative analysis revealed 7 peptides with more than 2-fold upregulation,
      especially a 4.96-fold increase detected in the phytosulfokine (PSK) peptide. To
      further evaluate effects of PSK1 on fruit chilling tolerance, weight loss,
      firmness and internal browning were investigated in PSK1-treated loquat fruit at
      0 degrees C. By contrast, these chilling injury symptoms were effectively reduced
      by PSK1. PSK1 markedly delayed decreases of ATP content and energy charge. The
      PSK1-treated fruit exhibited significantly lower activities of cell-wall
      degrading enzymes and transcripts of genes related to lignin synthesis. Our
      results demonstrated that PSK1 improves chilling tolerance of loquat fruit by
      maintaining high energy status and cell integrity. Peptidomics analysis provides
      a promising tool to discover some key peptides.

PMID- 28490096
TI  - Effects of high-speed homogenization and high-pressure homogenization on
      structure of tomato residue fibers.
AB  - Tomato residue fibers obtained after derosination and deproteinization were
      processed by high-speed homogenization (HSH) and high-pressure homogenization
      (HPH), and their effects on fiber structure was investigated, respectively.
      Characterizations including particle size distribution, SEM, TEM and XRD were
      performed. HSH could break raw fibers to small particles of around 60MUm, while
      HPH could reshape fibers to build network structure. Microfibrils were released
      and their nanostructure consisting of elementary fibrils was observed by TEM. XRD
      patterns indicated both HSH and HPH could hardly alter the nanostructure of the
      fibers. Physicochemical properties including expansibility, WHC and OHC were
      determined. Both HSH and HPH could increase the soluble fiber content by about
      8%, but HSH-HPH combined processing did not show better result. Acid (4mol/L HCl)
      was used in replacement of water medium and the acidic degradation of fibers
      could be promoted by high speed shearing or high pressure processing.

PMID- 28490098
TI  - Unravelling important odorants in horseradish (Armoracia rusticana).
AB  - Horseradish (Armoracia rusticana) is a plant well known for its roots' spicy
      aroma. The present study investigates the main aroma constituents of horseradish
      roots in general by analysing the aroma profiles of six different horseradish
      varieties, with one variety grown in two different soils. Odorants were
      characterised by means of gas chromatography-olfactometry and identified via
      their mass spectra, retention indices on two columns with different polarity, and
      their characteristic odour. A series of new aroma compounds from different
      substance groups were identified that have hitherto not been described in
      horseradish. Moreover, several of these constituents were successfully shown to
      exhibit high odour potency, alongside a high potential to influence the overall
      aroma of horseradish roots, like (3S,3aS,7aR)-wine lactone and 3-isopropyl-2
      methoxypyrazine.

PMID- 28490097
TI  - Influence of l-pyroglutamic acid on the color formation process of non-enzymatic
      browning reactions.
AB  - Heating aqueous d-glucose model reactions with l-glutamine and l-alanine yielded
      similar colored solutions. However, size-exclusion chromatography (SEC) revealed
      that both non-enzymatic browning reactions proceeded differently. Due to a fast
      occurring cyclization of l-glutamine to pyroglutamic acid, the typical amino
      carbonyl reaction was slowed down. However, l-glutamine and l-alanine model
      reactions showed the same browning index. Closer investigations could prove that
      l-pyroglutamic acid was able to influence non-enzymatic browning reactions. SEC
      analyses of d-glucose model reactions with and without l-pyroglutamic acid
      revealed an increase of low molecular colored compounds in the presence of l
      pyroglutamic acid. Polarimetric measurements showed a doubling of d-glucose
      mutarotation velocity and HPLC analyses of d-fructose formation during thermal
      treatment indicated a tripling of aldose-ketose transformation in the presence of
      l-pyroglutamic acid, which are signs of a faster proceeding non-enzymatic
      browning process. 2-Pyrrolidone showed no such behavior, thus the additional
      carboxylic group should be responsible for the observed effects.

PMID- 28490099
TI  - Phenolic profiles and metal ions analyses of pulp and peel of fruits and seeds of
      quince (Cydonia oblonga Mill.).
AB  - Six hydroxycinnamic acids were identified and determined quantitatively in
      methanol and acetone extracts from quince peel and pulp, namely 3-O
      caffeoylquinic acid (3-CQA), 4-p-coumaroylquinic acid (HC1), 4-O-caffeoylquinic
      acid (4-CQA), 5-O-caffeoylquinic acid (5-CQA), derivative of p-coumaroylquinic
      acid (HC2) and 3,5-dicaffeoylquinic acid (3,5-diCQA). The most abundant
      hydroxycinnamic acid was 5-CQA (neochlorogenic acid) with 259.12-481.4mg/kgf.w.
      in peel and 97.33-217.36mg/kg in quince pulp. Six flavonols were determined in
      the extracts from quince, quercetin-3-galactoside (Q-Ga), quercetin-3-rutinoside
      (Q-Ru), quercetin-3-glucoside (Q-Glu), kaempferol-3-rutinoside (K-Ru), kaempferol
      3-glucoside (K-Glu) and derivative of quercetin produced in the reaction between
      quercetin-glucoside and p-coumaric acid (Q-Glu-p-CouA). Elemental analysis of
      quince seeds has not been performed previously. Also, using principal component
      and cluster analyses, we determined a strong negative relationship between total
      phenols and flavonoids, and Ni and Pb, specifically higher concentrations of
      these compounds were associated with lower concentrations of these metals.

PMID- 28490100
TI  - Plasma modification of starch.
AB  - Plasma is a medium of unbound negative and positive particles with the overall
      electrical charge being roughly zero. Non-thermal plasma processing is an
      emerging green technology with great potential to improve the quality and
      microbial safety of various food materials. Starch is a major component of many
      food products and is an important ingredient for food and other industries. There
      has been increasing interest in utilizing plasma to modify the functionalities of
      starch through interactions with reactive species. This mini-review summarises
      the impact of plasma on composition, chemical and granular structures,
      physicochemical properties, and uses of starch. Structure-function relationships
      of starch components as affected by plasma modifications are discussed. Effect of
      plasma on the properties of wheat flour, which is a typical example of starch
      based complex food systems, is also reviewed. Future research directions on how
      to better utilise plasma to improve the functionalities of starch are suggested.

PMID- 28490101
TI  - Feasibility of discrimination of dairy creams and cream-like analogues using
      Raman spectroscopy and chemometric analysis.
AB  - Dairy cream and its analogues with sunflower oil, coconut oil and palm oil in
      different milk fat/vegetable fat ratios were prepared and analysed using Raman
      spectroscopy. The linear discriminant analysis was conducted in order to classify
      the samples. Samples were well separated and displayed distinguishing linear
      arrangement along the principal component that expressed the variation in lipid
      unsaturation. Good separation of sunflower oil and milk fat samples was obtained
      in contrast to the samples with coconut and palm oil, where the substantial
      overlapping occurred. The method permitted classifying of the samples in terms of
      the type of fat used. Calibrated model was extremely sensitive (100%) for dairy
      cream. The results indicated that it is possible to consider the Raman
      spectroscopy coupled with chemometric analysis as a rapid way for the detection
      of dairy cream adulteration with sunflower, coconut and palm oils.

PMID- 28490102
TI  - Effect of grape juice press fractioning on polysaccharide and oligosaccharide
      compositions of Pinot meunier and Chardonnay Champagne base wines.
AB  - Press fractioning is an important step in the production of sparkling base wines
      to segregate the grape juices with different qualities. Grape juice fractions
      were collected during the pressing cycle at industrial and laboratory scales. The
      Pinot meunier and Chardonnay Champagne base wines obtained from the free-run
      juice and the squeezed juices exhibited strong differences from the beginning to
      the last step of pressing cycle for numerous enological parameters. Significant
      changes in polysaccharide (PS) and oligosaccharide (OS) base wine composition and
      concentration were found as the pressing cycle progressed. During the pressing
      cycle, the total PS concentration decreased by 31% (from 244 to 167mg/L) and 32%
      (from 201 to 136mg/L) in the Pinot meunier and Chardonnay wines respectively. The
      wine OS amounts varied between 97 and 139mg/L. The polysaccharide rich in
      arabinose and galactose (39-54%) and mannoproteins (38-55%) were the major PS in
      the base wines.

PMID- 28490103
TI  - Speciation analysis of organoarsenic compounds in livestock feed by microwave
      assisted extraction and high performance liquid chromatography coupled to atomic
      fluorescence spectrometry.
AB  - The development of a new method to determine the presence of the organoarsenic
      additives p-arsanilic acid (ASA), roxarsone (ROX) and nitarsone (NIT) in
      livestock feeds by high performance liquid chromatography coupled to ultraviolet
      oxidation hydride generation atomic fluorescence spectrometry (HPLC-UV/HG-AFS)
      after microwave assisted extraction (MAE) was proposed. Chromatographic
      separation was achieved on a C18 column with 2% acetic acid/methanol (96:4, v/v)
      as the mobile phase. The limits of detection (LODs) were 0.13, 0.09 and 0.08mgL
      1, and the limits of quantification (LOQs) were 0.44, 0.30 and 0.28mgL-1. The
      relative standard deviations (RSDs) for ASA, ROX and NIT determined from five
      measurements of the mixed calibration standard were 3.3, 5.3, and 5.4%,
      respectively. MAE extraction of phenylated arsenic compounds using 1.5M H3PO4 at
      120 degrees C for 45min allowed for maximum recoveries (%) of total arsenic (As)
      and organoarsenic species, with no degradation of these compounds. The extraction
      of total As was approximately 97%, and the As species recoveries were between
      95.2 and 97.0%. The results of the analysis were validated using mass balance by
      comparing the sum of extracted As with the total concentration of As in the
      corresponding samples. The method was successfully applied to determine the
      presence of these compounds in feed samples. ASA was the only As species detected
      in chicken feed samples, with a concentration between 0.72 and 12.91mgkg-1.

PMID- 28490104
TI  - First approach to assess the bioaccessibility of bisphenol A in canned seafood.
AB  - Human health risks due to bisphenol A (BPA) exposure through canned food
      consumption are an emerging safety concern worldwide. In this study, an in vitro
      digestion model was used to simulate human digestion and evaluate BPA
      bioaccessibility in canned seafood for the first time. BPA contents of canned
      tuna and sardine samples and their bioaccessible and non-bioaccessible fractions
      were determined by gas chromatography coupled to mass spectrometry (GC-MS). The
      21 samples of canned tuna and sardines, all from the same producer but with
      different kind of sauces, showed BPA levels ranging from <1ugkg-1 (limit of
      quantification, LOQ) to 62ugkg-1, with variable results within and between sample
      groups. BPA bioaccessibility was evaluated in six positive samples, with values
      ranging from 80 to 99%. The results suggest that BPA bioaccessibility was
      slightly lower in samples with higher lipid content.

PMID- 28490105
TI  - A novel technology for the rapid, selective, magnetic removal of pathogenesis
      related proteins from wines.
AB  - Haze formation is a significant problem for the wine industry. A novel technology
      for the rapid, selective, magnetic removal of pathogenesis-related proteins from
      wine was developed. The pathogenesis-related proteins in nine different white
      wines were selectively captured and removed by acrylic acid plasma-coated
      magnetic nanoparticles. Treated white wines were analyzed for protein and
      phenolic content to assess the performance of the functionalized magnetic
      nanoparticles. The analysis showed that the acrylic acid coated magnetic
      nanoparticles effectively removed proteins and did not significantly change the
      phenolic composition of the wines. This new technology may become an alternative
      to conventional bentonite treatment which has economic and sensory impacts in the
      wine production process. Furthermore, such rapid separation technology for the
      binding and removal of proteins could benefit other areas such as diagnostics,
      water treatment, biotechnology and therapeutics.

PMID- 28490106
TI  - Inactivation of soybean trypsin inhibitor by dielectric-barrier discharge (DBD)
      plasma.
AB  - Soybean trypsin inhibitor (STI) is considered as one of the most important anti
      nutritional factors in soybeans. The objective of this study was to investigate
      the impacts and underling mechanisms of dielectric-barrier discharge (DBD) plasma
      on STI activities. The results shown that DBD plasma treatment significantly
      induced the inactivation of STI in soymilk and Kunitz-type trypsin inhibitor from
      soybean (SKTI) in a model system. After exposure to DBD plasma at 51.4W for
      21min, the STI activities of soymilk were reduced by 86.1%. Affter being treated
      by DBD plasma, the intrinsic fluorescence and surface hydrophobicity of SKTI were
      significantly decreased, while the sulfhydryl contents were increased. It is
      assumed that DBD plasma-induced conformational changes and oxidative modification
      might contribute to the inactivation of SKTI. In summary, DBD plasma technology
      is a potential alternative to heat treatment for the inactivation of anti
      nutritional substances in food legumes.

PMID- 28490107
TI  - Simultaneous estimation of scavenging capacities of peach extract for multiple
      reactive oxygen species by fluorescence fingerprint method.
AB  - In this study, the potential of using fluorescence fingerprint, also known as
      fluorescence excitation-emission matrix, for estimating the scavenging capacity
      of peach extract on reactive oxygen species (ROS) was investigated. Samples from
      each of the five cultivars (Asama Hakuto, Hakuho, Kawanakajima Hakuto, Natsukko
      and Ougonto) were freeze-dried and crushed. The scavenging capacities of peach
      extracts for the target ROS (hydroxyl, superoxide, alkoxyl radicals and singlet
      oxygen) were measured by electron paramagnetic resonance spin trapping method.
      Fluorescence fingerprints of the same samples were obtained. Partial least
      squares regression analysis was carried out to develop prediction models for ROS
      scavenging capacity. The models were assessed by external validation.
      Fluorescence fingerprint was found to accurately estimate the scavenging capacity
      for the alkoxyl and superoxide radicals with the prediction error of
      0.06mmoltroloxeq./mL and 0.31mmolalpha-lipoicacideq./mL with a coefficient of
      determination of prediction (R2P) of 0.78 and 0.91, respectively.

PMID- 28490108
TI  - Evaluation of 2-acetyl-1-pyrroline in foods, with an emphasis on rice flavour.
AB  - The popcorn-like aroma compound 2-acetyl-1-pyrroline (2-AP) is a key contributor
      to the desirable aroma of fragrant rice and is also important in the aroma of
      other foods, such as pandan leaf, popcorn and Mediterranean sausage. It can be
      formed enzymatically in the rice grain as it grows and is also formed, as part of
      the Maillard reaction, when rice is heated. This review examines the formation of
      2-AP in rice and other foods, particularly its formation during cooking, focusing
      on the importance of the Maillard reaction between reducing sugar breakdown
      products and 1-pyrroline derived from the amino acids proline and ornithine. The
      synthesis of 2-AP is discussed alongside the attempts that have been made to
      stabilise this relatively unstable compound. The analysis of 2-AP by instrumental
      techniques, particularly gas chromatography-mass spectrometry and gas
      chromatography-olfactometry, alongside the use of sensory studies, is also
      discussed.

PMID- 28490109
TI  - Effect of complexes of cyanidin-3-diglucoside-5-glucoside with rutin and metal
      ions on their antioxidant activities.
AB  - Studies have enabled a molecular understanding of the anthocyanin copigmentation
      phenomenon over several decades. However, the effect of combinations of, or even
      supramolecular assemblies of, anthocyanins with other phenols and/or metal ions
      on their antioxidative activity was unclear. In this study, anthocyanin complexes
      of cyanidin-3-diglucoside-5-glucoside (CY3D5G), rutin and Mg(II)/Fe(III) were
      constructed, analyzed, and evaluated for their antioxidant effects. The CY3D5G
      rutin-Fe(III) exhibited supramolecular properties via visible, CD and FTIR
      spectra among complexes. The interaction of CY3D5G-rutin, CY3D5G-rutin-Mg(II), or
      CY3D5G-rutin-Fe(III) was synergistic (P<0.05) in the ORAC assay. On cellular ROS
      levels, the median effective concentration of the CY3D5G-rutin-Mg(II) was
      7.76MUmol QE/L and exhibited a synergistic interaction (CI=0.67, P<0.05), whereas
      the CY3D5G-rutin-Fe(III) (CI=0.79, P=0.074) was additive. The results indicate
      that the antioxidant properties were affected by the molecular combination.
      Additionally, Fe(III) might exhibit a negative effect, since the CY3D5G-Fe(III)
      required a greater concentration than CY3D5G to achieve the same effect on cells.

PMID- 28490110
TI  - Multivariate statistical analysis of the polyphenolic constituents in kiwifruit
      juices to trace fruit varieties and geographical origins.
AB  - Fifty-one kiwifruit juice samples of seven kiwifruit varieties from five regions
      in China were analyzed to determine their polyphenols contents and to trace fruit
      varieties and geographical origins by multivariate statistical analysis. Twenty
      one polyphenols belonging to four compound classes were determined by ultra-high
      performance liquid chromatography coupled with ultra-high-resolution TOF mass
      spectrometry. (-)-Epicatechin, (+)-catechin, procyanidin B1 and caffeic acid
      derivatives were the predominant phenolic compounds in the juices. Principal
      component analysis (PCA) allowed a clear separation of the juices according to
      kiwifruit varieties. Stepwise linear discriminant analysis (SLDA) yielded
      satisfactory categorization of samples, provided 100% success rate according to
      kiwifruit varieties and 92.2% success rate according to geographical origins. The
      result showed that polyphenolic profiles of kiwifruit juices contain enough
      information to trace fruit varieties and geographical origins.

PMID- 28490111
TI  - Effect of high hydrostatic pressure and retrogradation treatments on structural
      and physicochemical properties of waxy wheat starch.
AB  - In this study, the effects of high hydrostatic pressure and retrogradation (HHPR)
      treatments on in vitro digestibility, structural and physicochemical properties
      of waxy wheat starch were investigated. The waxy wheat starch slurries (10%, w/v)
      were treated with high hydrostatic pressures of 300, 400, 500, 600MPa at 20
      degrees C for 30min, respectively, and then retrograded at 4 degrees C for 4d.
      The results indicated that the content of slowly digestible starch (SDS) in HHPR
      treated starch samples increased with increasing pressure level, and it reached
      the maximum (31.12%) at 600MPa. HHPR treatment decreased the gelatinization
      temperatures, the gelatinization enthalpy, the relative crystallinity and the
      peak viscosity of the starch samples. Moreover, HHPR treatment destroyed the
      surface and interior structures of starch granules. These results suggest that
      the in vitro digestibility, physicochemical, and structural properties of waxy
      wheat starch are effectively modified by HHPR.

PMID- 28490112
TI  - Real-time monitoring of sucrose, sorbitol, d-glucose and d-fructose concentration
      by electromagnetic sensing.
AB  - Magnetic sensing at microwave frequencies for real-time monitoring of sucrose,
      sorbitol, d-glucose and d-fructose concentrations is reported. The sensing
      element was designed based on a coplanar waveguide (CPW) loaded with a split ring
      resonator (SRR), which was fabricated on a DiClad 880 substrate with a thickness
      of 1.6mm and relative permittivity (epsilonr) of 2.2. The magnetic sensor was
      connected to a Vector Network Analyzer (VNA) and the electromagnetic interaction
      between the samples and sensor was analyzed. The magnitude of the transmission
      coefficient (S21) was used as an indicator to detect the solution sample
      concentrations ranging from 0.04 to 0.20g/ml. The experimental results confirmed
      that the developed system using microwaves for the real-time monitoring of
      sucrose, sorbitol, d-glucose and d-fructose concentrations gave unique results
      for each solution type and concentration. Moreover, the proposed sensor has a
      wide dynamic range, high linearity, fast operation and low-cost.

PMID- 28490113
TI  - Mitigating the in vitro enzymatic digestibility of noodles by aqueous extracts of
      Malay cherry leaves.
AB  - Aqueous extracts of Malay cherry leaves was incorporated into wheat, rice,
      tapioca, and potato flours with the purpose to formulate noodles with slow
      digestibility. In vitro digestion studies of these noodle prototypes were carried
      out to evaluate their digestibility under simulated gastrointestinal conditions.
      Upon incorporation of 2-8% of aqueous extracts, all four different types of
      noodles exhibited dose dependency with varying degree of digestibility. The
      greatest reduction in digestibility was observed in 8% tapioca noodles (69.2%)
      after 180min. While there was no significant change on the physicochemical
      properties of the noodles incorporated with different levels of aqueous extracts,
      the color of noodles was darker. Overall, the results showed that incorporating
      aqueous extracts is a promising way to mitigate the digestibility of starch in
      different starchy foods. This study showed a viable way to produce starchy foods
      with low glycemic index (GI) suitable for people with postprandial hyperglycemia.

PMID- 28490114
TI  - Volatile organic compounds as markers of quality changes during the storage of
      wild rocket.
AB  - The quality of leafy green vegetables changes during storage. Leaves become
      yellow or disintegrate, and an off-odor may develop. In addition, small amounts
      of volatile organic compounds (VOCs) are released. In this study, the release of
      acetone, carbon disulfide, dimethyl sulfide, nitromethane, pentane, 3
      methylfuran, 2-ethylfuran, and dimethyl disulfide from wild rocket with different
      initial qualities was monitored during 8d storage at 10 degrees C and correlated
      to aerobic bacteria counts, yeast and mold counts, and degree of tissue
      disintegration. The release of VOCs, except for 3-methylfuran, was influenced by
      the initial quality of the leaves. The release of pentane and 2-ethylfuran was
      related to the degree of tissue disintegration, and the release of dimethyl
      sulfide and dimethyl disulfide was related to the total aerobic bacteria count.
      The results demonstrated that VOCs can be used as markers for monitoring the
      complex quality changes taking place in packaged fresh produce during storage.

PMID- 28490115
TI  - Mechanistic insights into tyrosinase-mediated crosslinking of soy glycinin
      derived peptides.
AB  - Tyrosinase from Bacillus megaterium (TyrBm) was previously used to modulate soy
      glycinin-based emulsions and gels. To study the crosslinking mechanism, TyrBm
      oxidation of three tyrosine-containing octapeptides derived from glycinin was
      analyzed by oxygen consumption measurements, absorbance and mass spectrometry. A
      significant lag period and lower activity were measured when tyrosine was located
      in the middle of the peptide chain. Mass spectrometry analysis showed that these
      peptides are crosslinked via the oxidative quinone ring of the tyrosine residue
      by aryl-alkylamine addition or aryloxy radical coupling to form di-DOPA (3,4
      dihydroxyphenylalanine). In contrast, peptides containing tyrosine in the N- or C
      terminus, were rapidly oxidized forming multimer units within thirty minutes.
      When small amino acids were adjacent to the terminus tyrosine, formation of di
      tyrosine was observed. This work confirms that protein crosslinking by TyrBm
      occurs by several chemical mechanisms and may assist in designing peptide-based
      inhibitors for the food and cosmetic applications.

PMID- 28490116
TI  - The effect of Maillard reaction products and yeast strain on the synthesis of key
      higher alcohols and esters in beer fermentations.
AB  - The effect of Maillard reaction products (MRPs), formed during the production of
      dark malts, on the synthesis of higher alcohols and esters in beer fermentations
      was investigated by headspace solid-phase microextraction GC-MS. Higher alcohol
      levels were significantly (p<0.05) higher in dark malt fermentations, while the
      synthesis of esters was inhibited, due to possible suppression of enzyme activity
      and/or gene expression linked to ester synthesis. Yeast strain also affected
      flavour synthesis with Saccharomyces cerevisiae strain A01 producing considerably
      lower levels of higher alcohols and esters than S288c and L04. S288c produced
      approximately double the higher alcohol levels and around twenty times more
      esters compared to L04. Further investigations into malt type-yeast strain
      interactions in relation to flavour development are required to gain better
      understanding of flavour synthesis that could assist in the development of new
      products and reduce R&D costs for the industry.

PMID- 28490117
TI  - Carotenoid retention in biofortified maize using different post-harvest storage
      and packaging methods.
AB  - Orange maize is being promoted as a source of provitamin A carotenoids (pVAC) in
      Zambia. Carotenoid retention in orange maize grains stored in metal silos,
      multilayer polyethylene and common woven bags, and maize meal packaged in single
      and multilayer polyethylene bags was evaluated. Significant differences in total
      pVAC retention were found between grain storage methods (48.1-57.2%) after
      6months of storage. Total pVAC retention in hammer meal (73.1-73.5%) was higher
      than in breakfast meal (64.3-69.3%) after 4months of storage; however, no
      differences in pVAC retention were found between meal types when stored in single
      and multilayer polyethylene bags. In general, beta-cryptoxanthin (betaCX) had
      higher retention than beta-carotene (betaC). Potential contribution of stored
      orange maize to the estimated average requirement of children and women was 26.5%
      and 24.3%, respectively. Orange maize meal can provide significant amounts of
      provitamin A to diets of Zambians even after 4months of storage.

PMID- 28490118
TI  - Study of phenolic extractability in grape seeds by means of ATR-FTIR and Raman
      spectroscopy.
AB  - Near infrared hyperspectral imaging has been applied to grape seeds in order to
      select a representative subset of samples according to their spectral features in
      the 900-1700nm range. Afterwards, selected grape seeds have been classified
      according to their total phenol and flavanol extractabilities. In this way,
      samples were sorted in three different groups identified as low, medium and high
      extractability levels. In order to establish the chemical structures which can be
      responsible for the different extractabilities, vibrational spectroscopy has been
      applied to the non-extracted material after seed extractions. Attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) and Raman spectra of non
      extracted seed material have been recorded and their main spectral features have
      been linked to extractabilities of flavanolic and total phenolic compounds. The
      vibrational spectroscopic analysis confirms that grape seed phenolic
      extractability is influenced by the cell wall composition (polysaccharides,
      lignins, pectins) and by the degree of esterification of pectins.

PMID- 28490119
TI  - Complex interactive effects of ripening degree, malaxation duration and
      temperature on Oblica cv. virgin olive oil phenols, volatiles and sensory
      quality.
AB  - The interactive effects of ripening degree, malaxation duration and temperature
      on Oblica cv. (Olea europaea L.) virgin olive oil phenols, volatiles, and sensory
      quality were investigated. Olives were picked at three ripening degrees with
      International Olive Council indices of 0.68, 2.48 and 4.10, and processed by
      malaxation at 22 and 30 degrees C, and at both temperatures for 30 and 60min.
      Ripening exhibited the strongest effect, and malaxation duration the weakest.
      Phenols were generally found to decrease during ripening; however 3,4-DHPEA-EDA
      and p-HPEA-EDA increased. Similar behaviour was observed for (E)-2-hexenal.
      Higher malaxation temperature induced an increase in particular important phenols
      and C6 alcohols, while C6 aldehydes mostly decreased. Interactions between the
      factors were established, mostly between ripening degree and malaxation
      temperature: the effect of the latter was most pronounced for ripe olives,
      especially for 3,4-DHPEA-EDA, p-HPEA-EDA and C6 volatiles. Sensory attributes
      were generally in agreement with the chemical composition.

PMID- 28490120
TI  - Evaluation of antioxidant potential of Artocarpus heterophyllus L. J33 variety
      fruit waste from different extraction methods and identification of phenolic
      constituents by LCMS.
AB  - Artocarpus heterophyllus J33 (AhJ33) fruit is a popular and valuable jackfruit
      variety in Malaysia. For export, the pulp has to be separated from the skin which
      is usually discarded. Hence, the conversion of the fruit waste to food products
      with economic value needs to be explored utilizing the waste to wealth concept.
      This paper reports the evaluation of antioxidant potential of AhJ33 fruit waste
      (rind and rachis) extracts from three different extraction methods (maceration,
      percolation and Soxhlet). The antioxidant potential was assessed by DPPH radical
      scavenging, FRAP and beta-carotene bleaching assays. The total phenolic and total
      flavonoid contents were estimated by TPC and the TFC assays. For both rind and
      rachis, the maceration technique yielded extracts with the strongest antioxidant
      activities which correlated with the highest TPC and TFC values. TOF LCMS
      analyses identified two phenolic acids as the major constituents responsible for
      the antioxidant activity of the active extracts.

PMID- 28490121
TI  - Isotope dilution HPLC-MS/MS for simultaneous quantification of acrylamide and 5
      hydroxymethylfurfural (HMF) in thermally processed seafood.
AB  - The objective of this study was to develop an accurate, robust and rapid HPLC
      MS/MS-based method capable of quantifying acrylamide and 5-hydroxymethylfurfural
      (HMF) simultaneously. A Phenomenex Synergi Fusion-RP C18 column (50mm*2.5mm,
      2MUm) was used, and the MS/MS instrument was operated in multiple reaction
      monitoring mode. The isotope dilution method was used to correct for the matrix
      effect from samples. This method demonstrated low limits of quantification
      (2.12ng/mL for acrylamide and 4.86ng/mL for HMF) and excellent linearity
      (R2>0.999). This method also demonstrated excellent quantification accuracy,
      precision, and recovery (87-110%). Using the method developed, target analytes
      were quantified in 14 thermally-processed seafood samples. Resulting
      concentrations ranged from 5.58 to 50.35MUg/kg for acrylamide, and from 12.54 to
      2276.44MUg/kg for HMF. The proposed isotope dilution HPLC-MS/MS method is a valid
      and rapid technique for simultaneous analysis of acrylamide and HMF in seafood.

PMID- 28490122
TI  - Anthocyanin condensed forms do not affect color or chemical stability of purple
      corn pericarp extracts stored under different pHs.
AB  - Purple corn is rich in anthocyanins, some of which are condensed with flavanols.
      The aim was to determine the impact of anthocyanin condensed forms extracted from
      purple corn pericarp on color and chemical stability at different pHs compared
      with the complete extract, and an extract without condensed forms. Extracts were
      dissolved at pH values ranging from 2.0 to 6.0 and stored for 12weeks at 22
      degrees C. Color stability of anthocyanins decreased as the pH increased. Slight
      color differences were observed throughout time at pH 2 (DeltaE from 0.2 to 3.6).
      After 12weeks, pH 6 caused substantial changes in color (DeltaE=17.7 to 47.5);
      and reduced the predicted half-life of total anthocyanins (ranging from 1.8 to
      3weeks), compared to pH 2 (44.6 to 60.7weeks). Condensed forms had degradation
      kinetics similar to monomeric anthocyanins. Purple corn pericarp pigments can be
      used in acid beverages with an acceptable shelf-life.

PMID- 28490123
TI  - Kinetics of conversion of dihydroxyacetone to methylglyoxal in New Zealand manuka
      honey: Part IV - Formation of HMF.
AB  - During a study of the conversion of dihydroxyacetone (DHA) to methylglyoxal (MGO)
      in maturing New Zealand manuka honey, the kinetics of formation of 5
      (hydroxymethyl)furfural (HMF) was studied at temperatures from 4 to 37 degrees C.
      Formation of HMF was first-order during an induction period and zero-order
      thereafter indicating that the mechanism includes the formation of certain
      critical intermediates and that these require time to build up; the duration of
      the induction period depended primarily upon temperature. The zero-order rate
      constant at 37 degrees C was the same for manuka honey and clover honey doped
      with 2000 or 10,000mg/kg DHA and for artificial honey with 2000mg/kg of DHA and
      either alanine or proline and alanine added. Zero-order rate constants for
      artificial honey with added amino acids were less than for a control without
      amino acids. A simulation was created to predict the formation of HMF over time
      at 37 degrees C in manuka honey.

PMID- 28490124
TI  - Explaining the antioxidant activity of some common non-phenolic components of
      essential oils.
AB  - Limonene, linalool and citral are common non-phenolic terpenoid components of
      essential oils, with attributed controversial antioxidant properties. The
      kinetics of their antioxidant activity was investigated using the inhibited
      autoxidation of a standard model substrate. Results indicate that antioxidant
      behavior of limonene, linalool and citral occurs by co-oxidation with the
      substrate, due to very fast self-termination and cross-termination of the
      oxidative chain. Rate constants kp and 2kt, (M-1s-1) at 30 degrees C were 4.5 and
      3.5*106 for limonene, 2.2 and 9.0*105 for linalool and 39 and 1.0*108 for citral.
      Behavior is bimodal antioxidant/pro-oxidant depending on the concentration.
      Calculations at the M05/6-311+g(2df,2p) level indicate that citral reacts
      selectively at the aldehyde C-H having activation enthalpy and energy
      respectively lower by 1.3 and 1.8kcal/mol compared to the most activated allyl
      position. Their termination-enhancing antioxidant chemistry might be relevant in
      food preservation and could be exploited under appropriate settings.

PMID- 28490125
TI  - Colour and in vitro quality attributes of walnuts from different growing
      conditions correlate with key precursors of primary and secondary metabolism.
AB  - Walnuts (Juglans regia L.) are well known for their flavour, nutritional and
      health properties. The light colour of walnuts is a quality attribute that leads
      to consumer preference. The aim of this study was to correlate attributes such as
      colour and antioxidant capacity with the precursors of primary and secondary
      metabolism. Two growing areas and four different colours of walnuts cv. Chandler
      from the central region of Chile were evaluated. Walnuts grown in the zone with
      Andes Mountains influence showed higher (p<0.05) sugar and unsaturated fatty acid
      contents, which could be attributed to lower minimum temperatures during seed
      filling. Extra light walnuts had higher (p<0.05) total phenolic compounds,
      antioxidant capacity and arbutin levels than amber walnuts. To the best of our
      knowledge, this is the first time that arbutin has been reported in walnuts and
      could provide the first insight into how enzymatic browning is prevented in the
      Chandler cultivar.

PMID- 28490126
TI  - Phytochemical profiles and antioxidant activity of processed brown rice products.
AB  - The phytochemical profiles and antioxidant activity of free, soluble-conjugated,
      and bound fractions of brown rice and its processed products (textured rice,
      cooked rice and rice noodle) were studied. Nineteen phenolic acids were
      identified. Trans-ferulic acid was the most abundant monomeric phenolic acid with
      trans-trans-8-O-4' diferulic acid being most abundant diferulic acid. Processing
      increased the content of free phenolic acids, but decreased the content of
      soluble-conjugated phenolic acids. The content of bound phenolic acids was
      increased by improved extrusion cooking technology and cooking, but not affected
      by rice noodle extrusion. The total phenolic contents and antioxidant activities
      of free and soluble-conjugated fractions were decreased after processing, whereas
      those of bound fraction were increased by improved extrusion cooking technology
      and cooking, but not affected by rice noodle extrusion. Results indicated that
      whole foods designed for reducing chronic disease risk need to consider the
      effects of processing on phytochemical profiles and antioxidant activity of whole
      grains.

PMID- 28490127
TI  - Milk bioactive peptide database: A comprehensive database of milk protein-derived
      bioactive peptides and novel visualization.
AB  - During processing and digestion, milk proteins are disassembled into peptides
      with an array of biological functions, including antimicrobial, angiotensin
      converting enzyme inhibition, antioxidant, opioid, and immunomodulation. These
      functions are summarized in numerous reviews, yet information on which peptides
      have which functions remains scattered across hundreds of research articles. We
      systematically searched the literature for all instances of bioactive peptides
      derived from milk proteins from any mammalian source. The data were compiled into
      a comprehensive database, which can be used to search for specific functions,
      peptides, or proteins (http://mbpdb.nws.oregonstate.edu). To review this large
      dataset, the bioactive peptides reported in the literature were visually mapped
      on the parent protein sequences, providing information on sites with highest
      abundance of bioactive peptides.

PMID- 28490129
TI  - Tyrosinase inhibitory mechanism of betulinic acid from Dillenia indica.
AB  - The fruit of Dillenia indica L. is extensively used as a food additive. Betulinic
      acid (BA) is the most prominent secondary metabolite present in D. indica. This
      study screened the bioassay guided isolation of BA from D. indica and explored
      its tyrosinase inhibitory mechanism. Half maximal inhibitory concentration (IC50)
      of BA were calculated as 13.93uM and 25.66uM for diphenolase and monophenolase.
      Enzyme kinetic analysis revealed that BA inhibited tyrosinase activity non
      competitively. Further, conformational analysis of tyrosinase with BA was
      measured by fluorescence and circular dichroism spectroscopy. These results
      implied that diminish rigidity of enzyme might disturb the catalytic conformation
      of tyrosinase. Moreover, In-silico analysis confirmed probable binding polar and
      non-polar region on the active site of tyrosinase. Based on these findings, we
      suggest that BA from D. indica may be useful in preventing enzymatic browning
      reactions in food products.

PMID- 28490128
TI  - Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine in tea and the
      factors affecting their formation.
AB  - The levels of Nepsilon-(carboxymethyl)lysine (CML) and Nepsilon
      (carboxyethyl)lysine (CEL) in 99 tea samples from 14 geographic regions,
      including 44 green, 7 oolong, 41 black, and 7 dark teas were determined by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The CML and CEL contents
      varied from 11.0 to 1701MUg/g tea and 4.6 to 133MUg/g tea, respectively. Dark tea
      presented the highest levels of CML and CEL, whereas green and oolong teas
      presented the lowest levels. Five kinds of catechins in the tea were also
      analyzed, and spearman's correlation coefficients showed that all the catechins
      negatively correlated with CML and CEL. The results suggested that withering,
      fermentation and pile fermentation may facilitate the formation of CML and CEL.
      Catechins might inhibit the formation of CML and CEL, but their inhibitory
      effects may be affected by tea processing. The results of this study are useful
      for the production of healthier tea.

PMID- 28490130
TI  - Formation of lactoferrin/sodium caseinate complexes and their adsorption
      behaviour at the air/water interface.
AB  - This research investigated the complexation behaviour between lactoferrin (Lf)
      and sodium caseinate (NaCas) before and after heat treatment. The results showed
      that heating facilitated their interaction and different complexes were formed at
      different Lf/NaCas ratios. The presence of low concentrations of NaCas resulted
      in the rapid precipitation of Lf, while no precipitation was observed at the
      NaCas concentrations higher than Lf/NaCas ratio of 2:1. The formed complexes at
      the ratio of 2:1 have an average diameter of 194+/-9.0nm and they exhibited a
      great capacity in lowering the air/water interfacial tension. Further increase of
      NaCas concentration to ratios of 1:1 and 1:2 resulted in the formation of smaller
      complexes with average diameters of 60+/-2.5nm. The complexes formed at these two
      ratios showed similar adsorption behaviour at the air/water interface and they
      exhibited lower capacity in decreasing the interfacial tension than the ratio of
      2:1.

PMID- 28490131
TI  - Influence of the chemical structure on the odor characters of beta-citronellol
      and its oxygenated derivatives.
AB  - beta-Citronellol, 1, and citronellyl acetate, 2, are renowned fragrant
      constituents in perfumes and flavoring agents in foods and beverages. Both
      substances smell citrussy, fresh and floral. To elucidate the structural features
      required for these sensory effects, six C-8 oxygenated derivatives of 1 and 2
      were synthesized and analytically characterized. All compounds were tested for
      their odor qualities and odor thresholds in air, revealing that there were no
      significant differences in odor impressions from the parent monoterpenes and
      their derivatives in most cases; however, substantial differences in their odor
      threshold values were observed, with beta-citronellol as the most potent
      (10ng/Lair) and 8-hydroxycitronellyl acetate as the least potent odorant
      (1261ng/Lair). 8-Oxocitronellyl acetate was the only compound that was described
      with divergent odor attributes, namely musty, rotten and coconut-like. 8
      Carboxycitronellol and 8-carboxycitronellyl acetate were found to be odorless.

PMID- 28490132
TI  - Heat-induced inactivation mechanism of soybean Bowman-Birk inhibitors.
AB  - Due to the complications of the soymilk system, the heat-induced Bowman-Birk
      inhibitor (BBI) inactivation mechanism is not well known. In this study, two BBI
      samples with low and high purities were prepared from soymilk. It was confirmed
      that three groups (A, C, and D) of BBI, which are contained in soybean seeds,
      were transferred into soymilk during processing. On heating, it was found that 1)
      the two subdomains of BBI were not equally heat stable, 2) the conformation of
      BBI gradually changed, 3) some amino acid residues (namely, cystine, serine and
      lysine) in BBI were degraded, 4) BBI did not tend to form intermolecular cross
      links with another BBI, but did slightly with non-BBI proteins. Based on some
      previous studies, the conformational change of BBI was attributed to beta
      elimination reactions on the amino acid residues of BBI and the subsequent
      intramolecular reactions induced by the products yielded by the beta-elimination
      reactions.

PMID- 28490133
TI  - Nano-ZnO/carboxymethyl cellulose-based active coating impact on ready-to-use
      pomegranate during cold storage.
AB  - Minimally processed pomegranate rapidly loses its overall quality because of high
      water loss and microbial contamination. Nano-ZnO in combination with
      carboxymethyl cellulose (CMC) coating was used on pomegranate arils. Arils were
      dipped for 4min in distilled water (control), 0.1 or 0.2% (w/v) nano-ZnO
      suspension and then ZnO treated arils were coated with 0.5% (w/v) CMC and stored
      for 12days at 4 degrees C. Coatings decreased total yeast+mold during 12days of
      storage while total mesophilic bacteria was decreased during 6days of storage.
      Coatings decreased weight loss and also the greatest juice percent was in coated
      arils. Soluble solids content decreased during storage with no significant
      difference between treatments. CMC+0.2% nano-ZnO suppressed total phenol changes.
      Total anthocyanin, vitamin C, and antioxidant capacity were higher in coated
      arils. These findings suggest that nano-ZnO+CMC coating has the potential to
      extend minimally processed pomegranate storage life.

PMID- 28490134
TI  - Changes in the structure and dissociation of soybean protein isolate induced by
      ultrasound-assisted acid pretreatment.
AB  - Structure and dissociation properties of soybean protein isolate (SPI) induced by
      ultrasound and acid were investigated. Results of solubility showed that
      ultrasound-assisted acid had no effect on the content of soluble aggregates in
      SPI. Increase of fluorescence intensity and red-shift of maximum emission
      wavelength indicated that acid induced molecular unfolding of SPI and exposure of
      hydrophobic groups. Circular dichroism spectra showed that ultrasound-assisted
      acid pretreatment resulted in increases in the alpha-helix content by 29.2% and
      random coils content by 8.3%, while beta-sheet decreased by 13.4% (P<0.05), as
      compared with those of control. Analysis of sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and atomic force microscope revealed that the contents of
      small subunits and particle increased significantly when SPI treated by
      ultrasound-assisted acid comparing with the SPI treated by single acid and
      ultrasound treatment. This study illustrated the ultrasound and acid have
      synergistic effect on the structure unfolding and dissociation of SPI.

PMID- 28490135
TI  - Polyunsaturated lipids and vitamin A oxidation during cod liver oil in vitro
      gastrointestinal digestion. Antioxidant effect of added BHT.
AB  - The extent of cod liver oil hydrolysis and oxidation during in vitro
      gastrointestinal digestion was investigated by Proton Nuclear Magnetic Resonance
      (1H NMR) and Solid Phase Microextraction-Gas Chromatography/Mass Spectrometry
      (SPME-GC/MS). These techniques evidenced the degradation of polyunsaturated omega
      3 and omega-6 lipids and, for the first time, that of vitamin A, naturally
      present in cod liver oil. Cis,trans-conjugated dienes associated with
      hydroperoxides, as well as monoepoxides, cis,trans-2,4-alkadienals, 4-hydroperoxy
      and 4-hydroxy-2-alkenals, and several vitamin A derived metabolites were
      generated. Moreover, the effect of the addition of the synthetic antioxidant 2,6
      di-tert-butyl-hydroxytoluene (BHT) at 20 and 800ppm was tackled. Both techniques
      showed BHT to be efficient in limiting oxidation reactions during digestion,
      almost inhibiting them at 800ppm. Therefore, the simultaneous intake of
      antioxidants with cod liver oil should be considered, in order to increase
      polyunsaturated lipid and vitamin A bioaccessibility and avoid formation of toxic
      oxidation compounds like oxygenated alpha,beta-unsaturated aldehydes.

PMID- 28490136
TI  - Antioxidative capacity and binding affinity of the complex of green tea catechin
      and beta-lactoglobulin glycated by the Maillard reaction.
AB  - Major green tea catechin, epigallocatechin-3-gallate (EGCG), binds non-covalently
      to numerous dietary proteins, including beta-lactoglobulin of cow's milk. The
      effects of glycation of proteins via Maillard reaction on the binding capacity
      for polyphenols and the antiradical properties of the formed complexes have not
      been studied previously. Binding constant of BLG glycated by milk sugar lactose
      to EGCG was measured by the method of fluorophore quenching. Binding of EGCG was
      confirmed by CD and FTIR. The antioxidative properties of the complexes were
      examined by measuring ABTS radical scavenging capacity, superoxide anion
      scavenging capacity and total reducing power assay. Glycation of BLG does not
      significantly influence the binding constant of EGCG for the protein.
      Conformational changes were observed for both native and glycated BLG upon
      complexation with EGCG. Masking effect of polyphenol complexation on the
      antioxidative potential of the protein was of the similar degree for both
      glycated BLG and native BLG.

PMID- 28490137
TI  - Fractionation and identification of novel antioxidant peptides from buffalo and
      bovine casein hydrolysates.
AB  - Buffalo and bovine caseins were hydrolysed by alcalase and trypsin to produce
      novel antioxidant peptides. The casein hydrolysates were purified using
      ultrafiltration (UF) and further characterized by RP-HPLC. The fractions produced
      higher antioxidant activities were identified for their peptides using LC MS/MS.
      All UF-VI (MW<1kDa) fractions showed higher antioxidant activity. Hydrolysate
      produced by alcalase for buffalo casein (UF-VI with 54.84-fold purification)
      showed higher antioxidant activity than that obtained by trypsin. Trypsin
      hydrolysate contained high amount of hydrophobic amino acids while alcalase
      hydrolysate consisted mainly of Ser, Arg, Ala and Leu. The antioxidant peptides
      identified by LC MS/MS were RELEE, MEDNKQ and TVA, EQL in buffalo casein
      hydrolysates produced by trypsin and alcalase, respectively. Mechanism and
      reaction pathways of selected antioxidant peptides with ABTS were proposed.
      Conclusively, buffalo casein provided antioxidant peptides similar to bovine,
      suggesting that buffalo casein is a novel source of antioxidant.

PMID- 28490138
TI  - Contamination of Chinese salted fish with volatile N-nitrosamines as determined
      by QuEChERS and gas chromatography-tandem mass spectrometry.
AB  - The QuEChERS sample preparation method and gas chromatography-tandem mass
      spectrometry were employed to determine nine volatile N-nitrosamines (VNAs) in
      Chinese salted fish. This method was validated by considering calibration plot
      linearity, selectivity, matrix effects, trueness, precision, limits of
      quantification and specificity. Fifty-four samples of Chinese salted fish
      obtained from five provinces were analyzed. The results indicated that the
      concentrations of one VNA, N-nitrosodimethylamine in 57.4% of the samples
      exceeded the acceptable limit (the China national standard value of 4MUgkg-1),
      and total VNA contents in 68.5% of the samples exceeded the acceptable United
      States Department of Agriculture limit of 10MUgkg-1 for cured meats. In addition,
      total VNAs in marine salted fish that exceeded the acceptable limit were
      statistically higher than those in freshwater salted fish. The present study
      suggests that VNA contamination in Chinese salted fish continues to be serious,
      and deserves stricter management by the authorities.

PMID- 28490139
TI  - Development of a competitive immunochromatographic assay for the sensitive
      detection of amantadine in chicken muscle.
AB  - Amantadine (AMD) is a prohibitive veterinary medicine in the entire world. In
      this study, a sensitive colloidal gold immunochromatographic assay (CGICA) was
      established for the rapid semi-quantitative detection of AMD in chicken muscle.
      Under optimal conditions, the detection results were obtained in 12min with a
      limit of detection for 1.80ng/mL. CGICA presented a good linear range from
      2.5ng/mL to 25ng/mL, with only 11.5% cross-reactivity with rimantadine. The
      recovery rates for the fortified samples were ranged from 81% to 120%. The
      coefficient of variation of the intra-assay and inter-assay was less than 15%.
      The accuracy of CGICA was confirmed by systematically comparing the result of the
      proposed method with enzyme-linked immunosorbent assay and ultra-high-performance
      liquid chromatography-tandem mass spectrometry. Given the advantages of its
      simplicity, convenience, and speediness, the proposed CGICA is suitable for the
      on-site rapid detection of AMD in chicken muscle.

PMID- 28490140
TI  - Evaluation of antioxidant capacity and flavor profile change of pomegranate wine
      during fermentation and aging process.
AB  - Antioxidant properties and flavor characteristic profile of pomegranate wine
      during winemaking were investigated. The total phenol content and radical
      scavenging activity exhibited a slightly decrease in the end edge. Punicalagins
      and gallic acid were revealed to be the most abundant phenolic compounds,
      followed by ellagic acid and vanillic acid. These constituents were mainly
      responsible for the effective antioxidant capacity of pomegranate wine. The major
      changes of flavor qualities occurred in the initial stage, particularly 0-4day of
      fermentation. Fermentation significantly reduced the relative content of
      aldehydes, ketones, heterocyclic and aromatic compounds, but promoted the
      generation of esters and alcohols. This is the first time of using E-nose and E
      tongue to monitor odour and taste changes in the brewing process of pomegranate
      wine. The study may provide a promising instruction for improving functional
      features and quality control of the pomegranate wine.

PMID- 28490141
TI  - Carotenoid profiling of red navel orange "Cara Cara" harvested from five regions
      in China.
AB  - Understanding the composition and content of carotenoids in red-flesh navel
      orange "Cara Cara" cultivated in different regions is valuable for its nutrition
      assessment and fruit processing control. Herein, the carotenoids of "Cara Cara"
      fruits, harvested from five typical citrus growing regions of China, were
      identified and quantified by HPLC-DAD coupled with HPLC-DAD-APCI-MS/MS. In
      saponified extracts, 19 free carotenoids including 8 carotenes and 11
      xanthophylls were identified. In unsaponified extracts, 83.83-93.83% xanthophylls
      were esterified and 19 esters were inferred, with the 9-cis-violaxanthin ester
      confirmed as the dominant component. The carotenoid contents showed difference
      among the "Cara Cara" fruits from different growing regions, which might be
      attributed to the local environmental conditions, and the temperature was found
      directly correlated with total carotenoids content of "Cara Cara". The data
      obtained in this study will facilitate the nutritional evaluation of "Cara Cara"
      and provide beneficial guidance for fruit processing.

PMID- 28490142
TI  - Relation between polyphenol profile and antioxidant capacity of different
      Argentinean wheat varieties. A Boosted Regression Trees study.
AB  - We report the polyphenol profile and antioxidant capacity (AC) of 12 Argentinean
      wheat varieties from different regions. The polyphenol profile was studied by
      HPLC-MS. The AC was measured by TEAC and FRAP. Twenty-five polyphenols were
      identified. ACA 315 and KLEIN GUERRERO varieties showed the highest content of
      polyphenols, whereas BIOINTA 3004, KLEIN CAPRICORNIO and LE 2330 showed the
      lowest one. ACA 315 presented the highest AC, while BIOINTA 3004 and KLEIN
      CAPRICORNIO showed the lowest one. Boosted Regression Trees (BRT) analyses helped
      finding significant correlations between AC and polyphenol profile, being
      hydroxybenzoic acid diglucoside, tryptophan, chrysoeriol-6,8-di-C-pentoside and
      isomers 4, 5, 9 and 12 of diferulic acids key compounds to explain the observed
      AC. To our knowledge, this is the first report on the interaction between the
      environment and wheat genotypes evaluated by BRT, showing how the whole
      polyphenol profile can explain the AC in wheat.

PMID- 28490143
TI  - Method for sampling and analysis of volatile biomarkers in process gas from
      aerobic digestion of poultry carcasses using time-weighted average SPME and GC
      MS.
AB  - A passive sampling method, using retracted solid-phase microextraction (SPME) -
      gas chromatography-mass spectrometry and time-weighted averaging, was developed
      and validated for tracking marker volatile organic compounds (VOCs) emitted
      during aerobic digestion of biohazardous animal tissue. The retracted SPME
      configuration protects the fragile fiber from buffeting by the process gas
      stream, and it requires less equipment and is potentially more biosecure than
      conventional active sampling methods. VOC concentrations predicted via a model
      based on Fick's first law of diffusion were within 6.6-12.3% of experimentally
      controlled values after accounting for VOC adsorption to the SPME fiber housing.
      Method detection limits for five marker VOCs ranged from 0.70 to 8.44ppbv and
      were statistically equivalent (p>0.05) to those for active sorbent-tube-based
      sampling. The sampling time of 30min and fiber retraction of 5mm were found to be
      optimal for the tissue digestion process.

PMID- 28490144
TI  - Influence of the chemical structure on the odor qualities and odor thresholds of
      guaiacol-derived odorants, Part 1: Alkylated, alkenylated and methoxylated
      derivatives.
AB  - Guaiacol and its derivatives are commonly found in nature and are known for their
      characteristic smoky, clove-like and vanilla-like smells. However, there is no
      systematic investigation of the smell properties of structurally related guaiacol
      derivatives. In order to establish a comprehensive database on this olfactorily
      interesting substance class, odor thresholds in air and odor qualities of
      guaiacol and its alkylated, alkenylated, and methoxylated derivatives were
      determined by means of gas chromatography-olfactometry. All compounds elicited
      characteristic smoky/smoked ham-like, vanilla-like/sweet and/or clove-like smell
      impressions. The odor thresholds of the compounds were generally very low,
      ranging from 0.00018 to 111ng/Lair. The lowest thresholds were determined for 5
      methoxyguaiacol and guaiacol, followed by 4-ethyl- and 4-vinylguaiacol. Some
      inter-individual differences in the threshold values between panelists were
      observed, with highest variation in the individual values of cis-6-propenyl-,
      trans-6-propenyl- and 3-vinylguaiacol. The smell impressions, on the other hand,
      were quite consistent.

PMID- 28490145
TI  - Thermal and high pressure inactivation kinetics of blueberry peroxidase.
AB  - This study for the first time investigated the stability and inactivation
      kinetics of blueberry peroxidase in model systems (McIlvaine buffer, pH=3.6, the
      typical pH of blueberry juice) during thermal (40-80 degrees C) and combined high
      pressure-thermal processing (0.1-690MPa, 30-90 degrees C). At 70-80 degrees C,
      the thermal inactivation kinetics was best described by a biphasic model with
      ~61% labile and ~39% stable fractions at temperature between 70 and 75 degrees C.
      High pressure inhibited the inactivation of the enzyme with no inactivation at
      pressures as high as 690MPa and temperatures less than 50 degrees C. The
      inactivation kinetics of the enzyme at 60-70 degrees C, and pressures higher than
      500MPa was best described by a first order biphasic model with ~25% labile
      fraction and 75% stable fraction. The activation energy values at atmospheric
      pressure were 548.6kJ/mol and 324.5kJ/mol respectively for the stable and the
      labile fractions.

PMID- 28490146
TI  - Development and optimization of an efficient qPCR system for olive authentication
      in edible oils.
AB  - The applicability of qPCR in olive-oil authentication depends on the DNA obtained
      from the oils and the amplification primers. Therefore, four olive-specific
      amplification systems based on the trnL gene were designed (A-, B-, C- and D-trnL
      systems). The qPCR conditions, primer concentration and annealing temperature,
      were optimized. The systems were tested for efficiency and sensitivity to select
      the most suitable for olive oil authentication. The selected system (D-trnL)
      demonstrated specificity toward olive in contrast to other oleaginous species
      (canola, soybean, sunflower, maize, peanut and coconut) and showed high
      sensitivity in a broad linear dynamic range (LOD and LOQ: 500ng - 0.0625pg). This
      qPCR system enabled detection, with high sensitivity and specificity, of olive
      DNA isolated from oils processed in different ways, establishing it as an
      efficient method for the authentication of olive oil regardless of its category.

PMID- 28490147
TI  - Thermal degradation kinetics of anthocyanins extracted from jucara (Euterpe
      edulis Martius) and "Italia" grapes (Vitis vinifera L.), and the effect of
      heating on the antioxidant capacity.
AB  - The effect of temperature on the degradation of anthocyanins in jucara and
      "Italia" grape extracts was determined between 50 and 90 degrees C. For both
      species, thermal degradation followed a first-order kinetic model. The decimal
      reduction time decreased with increasing temperature, and dependence on the
      thermodegradable factor was lower at higher temperatures. The anthocyanins from
      jucara degraded more slowly than those extracted from "Italia" grapes. The
      activation enthalpy and free energy of inactivation indicated an endothermic
      reaction, not spontaneous degradation, whereas the activation entropy suggested
      that the transition state has less structural freedom than that of the reactants.
      The antioxidant capacity of the extracts was reduced when subjected to 90 degrees
      C heat treatment, however, significant quantities of this bioactive compound
      still remained.

PMID- 28490148
TI  - Characterisation of aroma-active and off-odour compounds in German rainbow trout
      (Oncorhynchus mykiss). Part II: Case of fish meat and skin from earthen-ponds
      farming.
AB  - Odorous molecules in earthen-ponds rainbow trout aquaculture farming in Germany
      were investigated with a special focus on musty-earthy off-odorants. To this aim,
      fish meat and skin were extracted using solvent-assisted flavour evaporation
      (SAFE) and were mildly concentrated; extracts were subsequently analysed by means
      of one- and two-dimensional high-resolution gas chromatography coupled with mass
      spectrometry and olfactometry (GC-MS/O and 2D-HRGC-MS/O). Aroma extract dilution
      analysis (AEDA) of the solvent extracts revealed the presence of 76 odorants of
      which 75 were successfully identified. Thereby, rotundone (black pepper) is
      described for the first time as an odour-active substance in fish. Moreover, a
      series of compounds is described for the first time in German aquaculture rainbow
      trout fish, including, amongst others, (E,Z,Z)-2,4,7-tridecatrienal, (E)-4,5
      epoxy-(E)-2-decenal, 4-ethyloctanoic acid, 3-methylindole (skatole), d-limonene,
      and indole. The analytical findings were further compared to sensory evaluation
      of the samples, and previously obtained data on the respective aquacultural
      water.

PMID- 28490149
TI  - Aroma profile and sensory characteristics of a sulfur dioxide-free mulberry
      (Morus nigra) wine subjected to non-thermal accelerating aging techniques.
AB  - The present study was undertaken to assess accelerating aging effects of high
      pressure, ultrasound and manosonication on the aromatic profile and sensorial
      attributes of aged mulberry wines (AMW). A total of 166 volatile compounds were
      found amongst the AMW. The outcomes of the investigation were presented by means
      of geometric mean (GM), cluster analysis (CA), principal component analysis
      (PCA), partial least squares regressions (PLSR) and principal component
      regression (PCR). GM highlighted 24 organoleptic attributes responsible for the
      sensorial profile of the AMW. Moreover, CA revealed that the volatile composition
      of the non-thermal accelerated aged wines differs from that of the conventional
      aged wines. Besides, PCA discriminated the AMW on the basis of their main
      sensorial characteristics. Furthermore, PLSR identified 75 aroma compounds which
      were mainly responsible for the olfactory notes of the AMW. Finally, the overall
      quality of the AMW was noted to be better predicted by PLSR than PCR.

PMID- 28490150
TI  - A simple and sensitive vortex-assisted ionic liquid-dispersive microextraction
      and spectrophotometric determination of selenium in food samples.
AB  - In the present study, a novel and eco-friendly vortex-assisted ionic liquid-based
      microextraction method was developed for the determination of selenium in food.
      The microextraction method is based on the liberation of iodine in the presence
      of selenium; the liberated iodine reacts with I- to form I3-. Anionic I3- reacts
      with cationic crystal violet dye, and the product is extracted into 1-hexyl-3
      methylimidazolium hexafluorophosphate phase in the presence of Triton X-114. The
      proposed method is linear in the range of 2.0-70ugL-1 and has a detection limit
      of 9.8*10-2ugL-1. Relative standard deviations were 3.67% and 2.89% for the five
      replicate measurements of 14 and 35ugL-1 Se(IV), respectively. The proposed
      method was successfully applied to different food samples (NIST SRM 2976 mussel
      tissue, pepper, ginger, wheat flour, red lentil, traditional soup, cornflour,
      cornstarch, and garlic) after microwave digestion.

PMID- 28490151
TI  - Preface: Invited Issue Editor, Professor Joong-Uhn Choi, and the Era of
      Neuroendoscopy.

PMID- 28490152
TI  - Keyhole Approach and Neuroendoscopy for Cerebral Aneurysms.
AB  - Treating diseases in the field of neurosurgery has progressed concomitantly with
      technical advances. Here, as a surgical armamentarium for the treatment of
      cerebral aneurysms, the history and present status of the keyhole approach and
      the use of neuroendoscopy are reviewed, including our clinical data. The major
      significance of keyhole approach is to expose an essential space toward a target,
      and to minimize brain exposure and retraction. Among several kinds of keyhole
      approaches, representative keyhole approaches for anterior circulation aneurysms
      include superciliary and lateral supraorbital, frontolateral, mini-pterional and
      mini-interhemispheric approaches. Because only a fixed and limited approach angle
      toward a target is permitted via the keyhole, however, specialized surgical
      devices and preoperative planning are very important. Neuroendoscopy has helped
      to widen the indications of keyhole approaches because it can supply illumination
      and visualization of structures beyond the straight line of microscopic view. In
      addition, endoscopic indocyanine green fluorescence angiography is useful to
      detect and correct any compromise of the perforators and parent arteries, and
      incomplete clipping. The authors think that keyhole approach and neuroendoscopy
      are just an intermediate step and robotic neurosurgery would be realized in the
      near future.

PMID- 28490153
TI  - Prevention of Complications in Endoscopic Third Ventriculostomy.
AB  - A variety of complications in endoscopic third ventriculostomy have been
      reported, including neurovascular injury, hemodynamic alterations, endocrinologic
      abnormalities, electrolyte imbalances, cerebrospinal fluid leakage, fever and
      infection. Even though most complications are transient, the overall rate of
      permanent morbidity is 2.38% and the overall mortality rate is 0.28%. To avoid
      these serious complications, we should keep in mind potential complications and
      how to prevent them. Proper decisions with regard to surgical indication, choice
      of endoscopic entry and trajectory, careful endoscopic procedures with anatomic
      orientation, bleeding control and tight closure are emphasized for the prevention
      of complications.

PMID- 28490154
TI  - From Exoscope into the Next Generation.
AB  - An exoscope, high-definition video telescope operating monitor system to perform
      microsurgery has recently been proposed an alternative to the operating
      microscope. It enables surgeons to complete the operation assistance by
      visualizing magnified images on a display. The strong points of exoscope are the
      wide field of view and deep focus. It minimized the need for repositioning and
      refocusing during the procedure. On the other hand, limitation of magnifying
      object was an emphasizing weak point. The procedures are performed under 2D
      motion images with a visual perception through dynamic cue and stereoscopically
      viewing corresponding to the motion parallax. Nevertheless, stereopsis is
      required to improve hand and eye coordination for high precision works.
      Consequently novel 3D high-definition operating scopes with various mechanical
      designs have been developed according to recent high-tech innovations in a
      digital surgical technology. It will set the stage for the next generation in
      digital image based neurosurgery.

PMID- 28490155
TI  - Endoscopic Treatment of Hypothalamic Hamartomas.
AB  - Hypothalamic hamartoma (HH) is a benign indolent lesion despite the presentation
      of refractory epilepsy. Behavioral disturbances and endocrine problems are
      additional critical symptoms that arise along with HHs. Due to its nature of
      generating epileptiform discharge and spreading to cortical region, various
      management strategies have been proposed and combined. Surgical approaches with
      open craniotomy or endoscopy, stereotactic approaches with radiosurgery and gamma
      knife surgery or radiofrequency thermos-coagulation, and laser ablation have been
      introduced. Topographical dimension and the surgeon's preference are key factors
      for treatment modalities. Endoscopic disconnection has been one of the most
      favorable options performed in treating HHs. Here we discuss presurgical
      evaluation, patient selection, surgical procedures, and complications.

PMID- 28490156
TI  - Multiloculated Hydrocephalus: Open Craniotomy or Endoscopy?
AB  - Multiloculated hydrocephalus (MLH) is a condition in which patients have
      multiple, separate abnormal cerebrospinal fluid collections with no communication
      between them. Despite technical advancements in pediatric neurosurgery,
      neurological outcomes are poor in these patients and the approach to this
      pathology remains problematic especially given individual anatomic complexity and
      cerebrospinal fluid (CSF) hydrodynamics. A uniform surgical strategy has not yet
      been developed. Current treatment options for MLH are microsurgical fenestration
      of separate compartments by open craniotomy or endoscopy, shunt surgery in which
      multiple catheters are placed in the compartments, and combinations of these
      modalities. Craniotomy for fenestration allows better visualization of the
      compartments and membranes, and it can offer easy fenestration or excision of
      membranes and wide communication of cystic compartments. Hemostasis is more
      easily achieved. However, because of profound loss of CSF during surgery, open
      craniotomy is associated with an increased chance of subdural hygroma and/or
      hematoma collection and shunt malfunction. Endoscopy has advantages such as
      minimal invasiveness, avoidance of brain retraction, less blood loss, faster
      operation time, and shorter hospital stay. Disadvantages are also similar to
      those of open craniotomy. Intraoperative bleeding can usually be easily managed
      by irrigation or coagulation. However, handling of significant intraoperative
      bleeding is not as easy. Currently, endoscopic fenestration tends to be performed
      more often as initial treatment and open craniotomy may be useful in patients
      requiring repeated endoscopic procedures.

PMID- 28490157
TI  - Endoscopic Third Ventriculostomy: Success and Failure.
AB  - Endoscopic third ventriculostomy (ETV) has now become an accepted mode of
      hydrocephalus treatment in children. Varying degrees of success for the procedure
      have been reported depending on the type and etiology of hydrocephalus, age of
      the patient and certain technical parameters. Review of these factors for
      predictability of success, complications and validation of success score is
      presented.

PMID- 28490158
TI  - Endoscopic Endonasal Approach for Suprasellar Lesions in Children: Complications
      and Prevention.
AB  - The endoscopic endonasal approach (EEA) has been popularized in adults and has
      been applied to an expanding range of surgical modules and indications in this
      population. However, its clinical application in pediatric neurosurgery has been
      impeded by the differences in anatomical features and the relatively low
      incidence of diseases to which it is applicable. In this review article, we
      mainly discuss the surgical indications, feasibility, and complications of EEA
      for suprasellar lesions in children based on a review of the literature, focusing
      especially on the age-related anatomical features of the nasal cavity, various
      pathologic entities, and the impact of EEA on long-term craniofacial growth.

PMID- 28490159
TI  - Neuroendoscopy: Current and Future Perspectives.
AB  - Neuroendoscopic surgery is performed because it causes minimal damage to normal
      structures, carries a lower rate of complications, and achieves excellent
      outcomes. Surgeons using an endoscope and related instruments can perform complex
      operations through very small incisions, which is especially useful for minimally
      invasive procedures for the brain and spine. Neuroendoscopic surgery is now
      performed in cases of obstructive hydrocephalus, various intraventricular
      lesions, hypothalamic hamartomas, craniosynostosis, skull base tumors, and spinal
      lesions. This review discusses the brief history of neuroendoscopy and the
      current state and future perspectives of endoscopic surgery.

PMID- 28490160
TI  - Transcortical Endoscopic Surgery for Intraventricular Lesions.
AB  - To review recent advances in endoscopic techniques for treating intraventricular
      lesions via transcortical passage. Articles in PubMed published since 2000 were
      searched using the keywords 'endoscopy,' 'endoscopic,' and 'neuroendoscopic.' Of
      these articles, those describing intraventricular lesions were reviewed.
      Suprasellar arachnoid cysts (SACs) can be treated with ventriculo-cystostomy (VC)
      or ventriculo-cysto-cisternostomy (VCC). VCC showed better results compared to
      VC. Procedure type, fenestration size, stent placement, and aqueductal patency
      may affect SAC prognosis. Colloid cysts can be managed using a transforaminal
      approach (TA) or a transforaminal-transchoroidal approach (TTA). However, TTA may
      result in better exposure compared to TA. Intraventricular cysticercosis can be
      cured with an endoscopic procedure alone, but if pericystic inflammation and/or
      ependymal reaction are seen, third ventriculostomy may be recommended. Tumor
      biopsies have yielded successful diagnosis rates of up to 100%, but tumor
      location, total specimen size, endoscope type, and vigorous coagulation on the
      tumor surface may affect diagnostic accuracy. An ideal indication for tumor
      excision is a small tumor with friable consistency and little vascularity. Tumor
      size, composition, and vascularity may influence a complete resection. SACs and
      intraventricular cysticercosis can be treated successfully using endoscopic
      procedures. Endoscopic procedures may represent an alternative to surgical
      options for colloid cyst removal. Solid tumors can be safely biopsied using
      endoscopic techniques, but endoscopy for tumor resection still results in
      considerable challenges.

PMID- 28490161
TI  - Endovascular Stroke Therapy Focused on Stent Retriever Thrombectomy and Direct
      Clot Aspiration: Historical Review and Modern Application.
AB  - Intravenous recombinant tissue plasminogen activator had been the only approved
      treatment for acute ischemic stroke since its approval in 1995. However, the
      restrictive time window, numerous contraindications, and its low recanalization
      rate were all limitations of this modality. Under those circumstances,
      endovascular stroke therapy went through a great evolution during the past two
      decades of intravenous thrombolysis. The results of the 2013 randomized trials
      for endovascular stroke therapy were neutral, although they were limited by
      insufficient imaging screening at enrollment, early-generation devices with less
      efficacy, and treatment delays. Huge progress was made in 2015, as there were
      five randomized clinical trials which all demonstrated the safety and efficacy of
      endovascular stroke treatment. Despite differences in detail patient enrollment
      criteria, all 5 trials employed key factors for good functional recovery; (1)
      screening with non-invasive imaging to identify the proximal occlusion and
      exclude a large infarct core, (2) using highly effective modern thrombectomy
      devices mainly with stent retriever, and (3) establishment of a fast workflow to
      achieve effective reperfusion. The results of those trials indicate that modern
      thrombectomy devices can allow for faster and more effective reperfusion, which
      can lead to improved clinical outcomes compared to intravenous thrombolysis
      alone. These advances in mechanical thrombectomy are promising in the global
      fight against ischemic stroke-related disability and mortality. Two current
      mainstreams among such mechanical thrombectomy techniques, "stent retriever
      thrombectomy" and "direct clot aspiration", are the topic of this review. Stent
      retriever thrombectomy using Solitaire and Trevo retriever will be firstly
      discussed. And, the commonalities and the differences between two major clot
      aspiration thrombectomy techniques; a direct aspiration first pass technique
      (ADAPT) and forced arterial suction thrombectomy (FAST), will be additionally
      explained. Finally, details regarding the combination of direct clot aspiration
      and stent retriever thrombectomy, the switching strategy and the Solumbra
      technique, will be described.

PMID- 28490162
TI  - Difference in Spinal Fusion Process in Osteopenic and Nonosteopenic Living Rat
      Models Using Serial Microcomputed Tomography.
AB  - OBJECTIVE: To identify and investigate differences in spinal fusion between the
      normal and osteopenic spine in a rat model. METHODS: Female Sprague Dawley rats
      underwent either an ovariectomy (OVX) or sham operation and were randomized into
      two groups: non-OVX group and OVX group. Eight weeks after OVX, unilateral lumbar
      spinal fusion was performed using autologous iliac bone. Bone density (BD) was
      measured 2 days and 8 weeks after fusion surgery. Microcomputed tomography was
      used to evaluate the process of bone fusion every two weeks for 8 weeks after
      fusion surgery. The fusion rate, fusion process, and bone volume parameters of
      fusion bed were compared between the two groups. RESULTS: BD was significantly
      higher in the non-OVX group than in the OVX group 2 days and 8 weeks after fusion
      surgery. The fusion rate in the non-OVX group was higher than that in the OVX
      group 8 weeks after surgery (p=0.044). The bony connection of bone fragments with
      transverse processes and bone formation between transverse processes in non-OVX
      group were significantly superior to those of OVX group from 6 weeks after fusion
      surgery. The compactness and bone maturation of fusion bed in non-OVX were
      prominent compared with the non-OVX group. CONCLUSION: The fusion rate in OVX
      group was inferior to non-OVX group at late stage after fusion surgery. Bone
      maturation of fusion bed in the OVX group was inferior compared with the non-OVX
      group. Fusion enhancement strategies at early stage may be needed to patients
      with osteoporosis who need spine fusion surgery.

PMID- 28490164
TI  - Contralateral Superior Cerebellar Artery Syndrome: A Consequence of Brain
      Herniation.
AB  - Vascular compromise is a well-known consequence of brain herniation syndromes.
      Transtentorial brain herniation most often involves posterior cerebral arteries.
      However, isolated involvement of contralateral superior cerebellar artery (SCA)
      during unilateral impending brain herniation is reported only once and we present
      another case of this exceedingly rare entity. A 24-year-old man was referred to
      us with impending herniation due to a multiloculated hydrocephalus, and during
      the course of illness, he developed an isolated SCA ischemia in the opposite side
      of the most dilated entrapped horn. In the current article we discuss the
      probable pathophysiologic mechanisms of this phenomenon, as well as recommending
      more inclusive brain studies in cases suspected of Kernohan-Woltman notch
      phenomenon in unilateral brain herniation. The rationale for this commentary is
      that contralateral SCA transient ischemia or infarct might be the underdiagnosed
      underlying pathomechanism of ipsilateral hemiparesis occurring in many cases of
      this somehow vague phenomenon.

PMID- 28490163
TI  - Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following
      Acute Severe Traumatic Brain Injury.
AB  - OBJECTIVE: The aim of this study to investigate the normal values of
      erythropoietin (EPO) and neuroprotective effects of quercetin and mannitol on EPO
      and hematocrit levels after acute severe traumatic brain injury (TBI) in rat
      model. METHODS: A weight-drop impact acceleration model of TBI was used on 40
      male Wistar rats. The animals were divided into sham (group I), TBI (group II),
      TBI+quercetin (50 mg/kg intravenously) (group III), and TBI+mannitol (1 mg/kg
      intravenously) (group IV) groups. The malondialdehyde, glutathione peroxidase,
      catalase, EPO, and hematocrit levels were measured 1 and 4 hour after injury. Two
      way repeated measures analysis of variance and Tukey's test were used for
      statistical analysis. RESULTS: The malondialdehyde levels decreased significantly
      after administration of quercetin and mannitol compared with those in group II.
      Catalase and glutathione peroxidase levels increased significantly in groups III
      and IV. Serum EPO levels decreased significantly after mannitol but not after
      quercetin administration. Serum hematocrit levels did not change significantly
      after quercetin and mannitol administration 1 hour after trauma. However,
      mannitol administration decreased serum hematocrit levels significantly after 4
      hour. CONCLUSION: This study suggests that quercetin may be a good alternative
      treatment for TBI, as it did not decrease the EPO levels.

PMID- 28490165
TI  - Remote Cerebellar Hemorrhage Presenting with Cerebellar Mutism after Spinal
      Surgery: An Unusual Case Report.
AB  - Dural injury during spinal surgery can subsequently give rise to a remote
      cerebellar hemorrhage (RCH). Although the incidence of such injury is low, the
      resulting hemorrhage can be life threatening. The mechanism underlying the
      formation of the hemorrhage is not known, but it is mostly thought to develop
      after venous infarction. Cerebellar mutism (CM) is a frequent complication of
      posterior fossa operations in children, but it is rarely seen in adults. The
      development of CM after an RCH has not been described. We describe the case of a
      65-year old female who lost cerebrospinal fluid after inadvertent opening of the
      dura during surgery. Computerized tomography performed when the patient became
      unable to speak revealed a bilateral cerebellar hemorrhage.

PMID- 28490166
TI  - Giant Ganglioneuroma of Thoracic Spine: A Case Report and Review of Literature.
AB  - Ganglioneuroma (GN) is a rare benign tumor of neural crest origin usually found
      in the abdomen, but may occasionally present at uncommon sites including the
      cervical, lumbar, or sacral spine. However, GNs of thoracic spine are extremely
      rare. In this report, we describe a 12-year-old girl with giant GN in the
      thoracic spine, who underwent successful resection (T1-4 level) of the tumor.
      Histopathological examination confirmed the diagnosis. GN should be considered in
      the differential diagnosis of any paraspinal mass. A high index of suspicion and
      correlation of clinico-radiological findings is necessary in differentiating a
      large benign tumor from a malignant growth. Complete surgical excision is the
      treatment of choice; however tumor size and location need to be considered for
      the surgical approach (one-step or multiple surgeries). Close follow-up after
      surgery is mandatory.

PMID- 28490167
TI  - Endoscopic Treatment of an Adult with Tegmental Astrocytoma Accompanied by
      Cerebrospinal Fluid Dissemination.
AB  - Midbrain gliomas are relatively rare neoplasms with a generally benign prognosis,
      with dissemination or metastasis not previously reported. We describe here a
      woman, in whom magnetic resonance imaging scans showed hydrocephalus and a
      tegmental lesion in the upper aqueduct. Endoscopic third ventriculostomy and
      biopsy were performed; during surgery, a second small lesion was observed in the
      infundibular recess. Histologically, the two lesions had the characteristics of
      low grade astrocytoma, suggesting that the midbrain astrocytoma may have been
      disseminated via the cerebral spinal fluid to the infundibular recess.
      Postoperatively this patient received radiotherapy for nearly one month. Although
      patients with these tumors are not usually administered adjunctive therapy,
      radiation and, combined modality therapy, including surgery, radiotherapy, and
      chemotherapy, may be beneficial in patients with midbrain gliomas with
      dissemination.

PMID- 28490168
TI  - Primary Glioblastoma of the Cerebellopontine Angle: Case Report and Review of the
      Literature.
AB  - Glioblastoma multiforme (GBM) is located most frequently in the cerebral
      hemispheres. Glioblastoma presenting as an extraaxial mass of cerebellopontine
      angle (CPA) is very rare in adults. We report a rare case of GBM arising in the
      CPA. The patient was a 71-year-old female, who complained of progressive gait
      disturbance and poor memory. Initial magnetic resonance imaging (MRI) revealed a
      1.4*1.3 cm mass in the left CPA, with broad base to the petrous bone, showing
      homogenous enhancement. Follow-up MRI showed a rapid increase in size of mass
      (2.7*2.2 cm) with a necrotic portion. A stereotactic biopsy was done under the
      guidance of navigation system, and the histopathologic diagnosis was GBM, World
      Heath Organization grade IV. Further surgical resection was not performed
      considering her general condition, and the patient underwent concurrent
      chemotherapy with radiation therapy. Although rare, the possibility of
      glioblastoma should be included in the differential diagnosis of atypical CPA
      tumor.

PMID- 28490169
TI  - Ethical considerations in the field of assisted reproductive technology.
AB  - Human reproduction has always generated more than its share of emotion that
      exceeds the life and death issues of medicine. For patients that are unable to
      conceive naturally, medical advances have greatly expanded treatment options.
      Assisted reproductive technology (ART) is a highly evolving, complex, and
      controversial field of medicine in which ethical principles play a large role in
      decision-making. The following highlights ethical considerations regarding ART,
      specifically in vitro fertilization (IVF), that practicing obstetricians and
      indeed all physicians may encounter. The aim was to encourage practitioners to
      consider these issues, and more, when developing guidelines for their own
      practice.

PMID- 28490170
TI  - Fertility preservation for social and oncofertility indications.
AB  - The desire to reproduce is a base human instinct. However, for many individuals,
      the chances of being able to have a genetic child are compromised by a number of
      factors. For some, therapies aimed at treating serious medical illness, such as
      cancer; result in a deleterious impact on the function of eggs and sperm in the
      future thus compromising future fertility. In women, a predictable decrease in
      egg quality and quantity occurs with advancing maternal age. Therefore, women who
      choose to delay childbearing until their late 30s or early 40s may experience
      fertility difficulties that would not have been present earlier in life.
      Currently, technologies exist that allow individuals to have an "insurance
      policy" to preserve eggs or sperm prior to being exposed to agents, including
      time or specific toxic agents to the ovaries or sperm, that may decrease
      fertility potential. This article attempts to summarize the current state of the
      art technologies regarding fertility preservation for both social and
      oncofertility indications.

PMID- 28490171
TI  - Management of perforation following stricture dilation.
AB  - Strictures can occur along any portions of the gastrointestinal tract for a
      variety of reasons and are commonly complicated by partial or complete
      obstruction. Endoscopic management of strictures is common, and generally safe.
      The most dreaded complication of stricture dilation is perforation due to high
      morbidity and mortality. The treatment of perforation following stricture
      dilation is commonly multidisciplinary and should involve gastrointestinal,
      surgical, and interventional radiology teams. A variety of devices and techniques
      are available to the endoscopist which now allow for successful endoscopic
      management of perforation in many cases.

PMID- 28490172
TI  - Antiviral Activities of Trichothecenes Isolated from Trichoderma albolutescens
      against Pepper Mottle Virus.
AB  - A bioassay-guided isolation using a green fluorescence protein (GFP)-tagged
      pepper mottle virus (PepMoV-GFP) based leaf-disk method to obtain new antiviral
      agents led to the isolation of trichodermin, 1, and a new compound
      trichoderminol, 2, from EtOAc extract of Trichoderma albolutescens culture
      medium. The structures of compounds 1 and 2 were determined by MS and NMR
      experiments, and the absolute configurations of the compounds were established by
      experimental and calculated vibrational circular dichroism spectra. Compounds 1
      and 2 were evaluated for their anti-PepMoV potential in systemic host plants,
      such as tobacco and pepper, by PepMoV-GFP based systemic host method. All
      compounds exhibited inactivation effects against PepMoV. Furthermore, compound 1
      showed protective effects against PepMoV.

PMID- 28490173
TI  - Applying Cadmium Relative Bioavailability to Assess Dietary Intake from Rice to
      Predict Cadmium Urinary Excretion in Nonsmokers.
AB  - Dietary Cd intake is often estimated without considering Cd bioavailability.
      Measured urinary Cd for a cohort of 119 nonsmokers with rice as a staple was
      compared to predicted values from rice-Cd intake with and without considering Cd
      relative bioavailability (RBA) in rice based on a steady state mouse kidney
      bioassay and toxicokinetic model. The geometric mean (GM) of urinary Cd and beta2
      microglobulin was 1.08 and 234 MUg g-1 creatinine. Applying Cd-RBA in foods to
      aggregate Cd intake (41.5 +/- 12.4, 48.0 +/- 9.3, 48.8 +/- 21.3% for rice, wheat,
      and vegetables), rice was the largest contributor (71%). For 63 participants
      providing paired urine and rice samples, the predicted GM of urinary Cd at 4.14
      MUg g-1 based on total Cd in rice was 3.5 times that of measured value at 1.20
      MUg g-1, while incorporating Cd-RBA to assess rice-Cd intake made the two closer
      with GM at 1.07 MUg g-1. The cohort findings were extended to a national scale,
      with urinary Cd for nonsmokers from rice Cd intake was mapped at province/city
      levels after considering rice Cd-RBA. Therefore, incorporating Cd bioavailability
      to assess dietary Cd intake is a valuable tool to accurately estimate human Cd
      exposure and associated health risk.

PMID- 28490174
TI  - Self-Organization of Electroactive Suspensions in Discharging Slurry Batteries: A
      Mesoscale Modeling Investigation.
AB  - We report a comprehensive modeling-based study of electroactive suspensions in
      slurry redox flow batteries undergoing discharge. A three-dimensional kinetic
      Monte Carlo model based on the variable step size method is used to describe the
      electrochemical discharge of a silicon/carbon slurry electrode in static mode
      (i.e., no fluid flow conditions). The model accounts for Brownian motion of
      particles, volume expansion of silicon upon lithium insertion, and formation and
      destruction of conducting carbon networks. Coupled to an electrochemical model,
      this study explores the impact of carbon fraction in the slurry and applied c
      rate on the specific capacity. The trends obtained are analyzed by following the
      behavior of parameters such as number of contacts between electroactive particles
      and the percentage of electroactive silicon particles. Furthermore, instead of
      studying the bulk behavior of the slurry, here the focus is given to the
      slurry/current collector interface in order to illustrate its importance. Hereby,
      it is demonstrated how this modeling tool can lead to deeper understanding and
      optimization of electroactive particle suspensions in redox flow batteries.

PMID- 28490176
TI  - Conformation of Ethylene Glycol in the Liquid State: Intra- versus Intermolecular
      Interactions.
AB  - Ethylene glycol is a typical rotor molecule with the three dihedral angles that
      allow for a number of possible conformers. The geometry of the molecule in the
      liquid state brings into sharp focus the competition between intra- and inter
      molecular interactions in deciding conformation. Here, we report a conformational
      analysis of ethylene glycol in the liquid state from ab initio molecular dynamics
      simulations. Our results highlight the importance of intermolecular hydrogen
      bonding over intramolecular interactions in the liquid, with the central OCCO
      linkage adopting both gauche and trans geometries in contrast to the gas phase,
      wherein only the gauche has been reported. The influence of intermolecular
      interactions on the conformation of the terminal CCOH moieties is even more
      striking, with certain regions of conformational space, wherein the ethylene
      glycol molecule cannot participate with its full complement of intermolecular
      hydrogen bonds, excluded. The results are in agreement with Raman and NMR
      spectroscopic studies of liquid ethylene glycol, but at the same time they are
      able to provide new insights into how intermolecular interactions favor certain
      conformations while excluding others.

PMID- 28490175
TI  - Prenatal Nonylphenol and Bisphenol A Exposures and Inflammation Are Determinants
      of Oxidative/Nitrative Stress: A Taiwanese Cohort Study.
AB  - Prenatal exposure to nonylphenol (NP) and/or bisphenol A (BPA) has been reported
      to be associated with adverse birth outcomes; however, the underlying mechanisms
      remain unclear. The primary mechanism is endocrine disruption of the binding
      affinity for the estrogen receptor, but oxidative stress and inflammation might
      also play a contributory role. We aimed to investigate urinary NP and BPA levels
      in relation to biomarkers of oxidative/nitrative stress and inflammation and to
      explore whether changes in oxidative/nitrative stress are a function of prenatal
      exposure to NP/BPA and inflammation in 241 mother-fetus pairs. Third-trimester
      urinary biomarkers of oxidative/nitrative stress were simultaneously measured,
      including products of oxidatively and nitratively damaged DNA (8-hydroxy-2'
      deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua)) as well as products of
      lipid peroxidation (8-iso-prostaglandin F2alpha (8-isoPF2alpha) and 4-hydroxy-2
      nonenal-mercapturic acid (HNE-MA)). The antioxidant glutathione peroxidase (GPx)
      and inflammation biomarkers, including C-reactive protein (CRP) and a panel of
      cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)),
      were analyzed in maternal and umbilical cord plasma samples. In adjusted models,
      we observed significant positive associations between NP exposure and 8-OHdG and
      8-NO2Gua levels, between BPA and 8-isoPF2alpha levels, and between maternal CRP
      levels and HNE-MA levels. Additionally, BPA and TNF-alpha levels in cord blood
      were inversely associated with maternal and GPx levels in cord blood as well as
      maternal TNF-alpha levels were inversely associated with maternal GPx levels.
      These results support a role for exposure to NP and BPA and possibly inflammation
      in increasing oxidative/nitrative stress and decreasing antioxidant activity
      during pregnancy.

PMID- 28490177
TI  - Synthesis of alpha-l-Threofuranosyl Nucleoside 3'-Monophosphates, 3'-Phosphoro(2
      Methyl)imidazolides, and 3'-Triphosphates.
AB  - alpha-l-Threofuranosyl nucleic acid (TNA) is an artificial genetic polymer
      composed of vicinal 2',3'-phosphodiester bonds linking adjacent threofuranosyl
      nucleosides. TNA is one of a small number of genetic polymers that are both
      highly resistant to nuclease digestion and capable of cross-pairing with DNA and
      RNA. Although an efficient method for synthesizing TNA nucleosides has been
      reported, very few advances have been made in the synthesis of phosphorylated TNA
      compounds. Here, we describe a highly efficient method for synthesizing alpha-l
      threofuranosyl nucleoside 3'-monophosphates (tNMPs), 3'-phosphoro(2
      methyl)imidazolides (2-MeImptNs), and 3'-triphosphates (tNTPs) bearing the four
      genetic bases of adenine (A), cytosine (C), thymine (T), and guanine (G). We
      suggest that this strategy, which provides access to grams of tNMPs, hundreds of
      milligrams of 2-MeImptNs, and tens of milligrams of tNTPs, will help advance the
      use of TNA monomers in exobiology and biotechnology applications.

PMID- 28490178
TI  - Atom Tunneling in the Hydroxylation Process of Taurine/alpha-Ketoglutarate
      Dioxygenase Identified by Quantum Mechanics/Molecular Mechanics Simulations.
AB  - Taurine/alpha-ketoglutarate dioxygenase is one of the most studied alpha
      ketoglutarate-dependent dioxygenases (alphaKGDs), involved in several
      biotechnological applications. We investigated the key step in the catalytic
      cycle of the alphaKGDs, the hydrogen transfer process, by a quantum
      mechanics/molecular mechanics approach (B3LYP/CHARMM22). Analysis of the charge
      and spin densities during the reaction demonstrates that a concerted mechanism
      takes place, where the H atom transfer happens simultaneously with the electron
      transfer from taurine to the Fe?O cofactor. We found the quantum tunneling of the
      hydrogen atom to increase the rate constant by a factor of 40 at 5  degrees C. As
      a consequence, a quite high kinetic isotope effect close to 60 is obtained, which
      is consistent with the experimental value.

PMID- 28490179
TI  - "Living" dynamics of filamentous bacteria on an adherent surface under
      hydrodynamic exposure.
AB  - The potential advantages of cell-based biohybrid devices over conventional
      nonliving systems drive the interest to control the behavior of the underlying
      biological cells in microdevices. Here, the authors studied how shear influenced
      the geometry and elongation of fimbriated filaments on affinity substrates. The
      cells were engineered to express FimH, which binds to mannose with a high
      affinity. A microfluidic channel was functionalized with RNAse B, which is rich
      in mannose residues, and the device was used to control the hydrodynamic force on
      live Escherichia coli under filamentous growth. It was discovered that
      filamentous E. coli cells adopt buckled geometry when the shear rate is low, but
      assume an extended geometry at high shear and align with the flow direction. The
      extension moves from bidirectional to preferentially downstream as the shear rate
      increases. Furthermore, living filaments slide easily on the substrate, and
      detach from the substrates at a rate nearly ten times greater than unfilamented
      live E. coli at high shear conditions (1000-4000 s-1). The hydrodynamic force and
      binding force experienced by the cells are further analyzed by COMSOL simulation
      and atomic force microscopy measurements, respectively, to explore the mechanism
      behind the living cell dynamics. Knowledge from this work helps guide design of
      interfacial properties and shear environments to control the geometry of living
      filamentous bacteria.

PMID- 28490180
TI  - "Category 4A" microcalcifications: how should this subcategory be applied to
      microcalcifications seen on mammography?
AB  - Background The BI-RADS provides descriptors for microcalcifications based on
      morphology and distribution. However, the descriptor for category 4A
      microcalcifications is not specified in the 5th BI-RADS nor in the prior
      editions. Purpose To investigate how the category 4A assessment is applied to
      suspicious microcalcifications, and the appropriate descriptors for category 4A
      assessment for microcalcifications seen on mammography. Material and Methods From
      June 2008 to November 2011, 296 women with 305 suspicious microcalcifications
      that were assessed as BI-RADS category 4A, who underwent imaging-guided biopsy or
      surgery, were included. Mammograms were reviewed and imaging features were
      analyzed according to the morphology and distribution descriptors of the 5th
      edition of BI-RADS. Pathological results were considered as the reference
      standard. Positive predictive values were calculated and compared between
      morphology and distribution descriptors. Results The overall positive predictive
      value (PPV) of category 4A microcalcifications was 17.7% (54/305). Most common
      descriptors for category 4A microcalcifications were amorphous morphology (73.1%)
      and grouped distribution (71.1%). PPVs of individual morphology descriptors were
      as follows: amorphous = 7.2%; coarse heterogeneous = 12.8%; fine pleomorphic or
      fine linear/fine linear branching = 91.4% ( P < 0.001). PPVs of distribution
      descriptors were as follows: regional = 13.2%; grouped = 16.1%; linear/segmental
      = 54.5% ( P < 0.001). For morphology and distribution descriptors combinations,
      PPVs for amorphous/regional and amorphous/grouped microcalcifications were 6.8%
      and 6.9%, while PPVs of other combinations were higher than 10%, respectively.
      Conclusion Common descriptors used in category 4A assessment for
      microcalcifications are amorphous morphology and grouped distribution. PPV of
      amorphous/regional and amorphous/grouped microcalcifications were suitable for
      category 4A assessment.

PMID- 28490181
TI  - Designing and evaluating autoverification rules for thyroid function profiles and
      sex hormone tests.
AB  - Purpose Following the analytical phase, the current practice of many hospital
      laboratories involves the manual verification of all test results followed by the
      production of the report. However, manual verification is a time-consuming and
      tedious process. In this paper, we provide a detailed description of how to
      design autoverification rules for thyroid function test profiles and sex
      hormones. Materials and methods We used DM2 (Data manager 2) to construct the
      algorithm and build the database for autoverification of thyroid function test
      profiles and sex hormones, with reference to Boolean logic, Auto 10-A and
      CLSI'88. The rules consist of checking quality control, instrument error flags,
      critical values, the analytical measurement range (AMR), the limit range,
      consistency check and delta check. Firstly, we established the rules in the DM2,
      collected clinical specimens for validation, then tested the rules in a 'live'
      environment. Results Agreement was achieved between manual verification by two
      senior laboratory personnel and verification using the autoverification rules in
      99.78% of the cases. The total autoverification rate for all tests was 77.06%.
      Following implementation of the rules, the laboratory turnaround time (TAT) was
      reduced by 54.55% and staffing numbers fell from three to two whole time
      equivalents (WTE). Statistical analysis resulted in a kappa statistic of 0.99 ( P
      < 0.001). Moreover, after implementing the autoverification rules, the error rate
      fell to 0.04%, indicating that errors were almost completely eliminated.
      Conclusion Implementing autoverification rules can reduce TAT, minimize the
      number of samples that require manual verification and allow for a reduction in
      staffing numbers. It also allows laboratory staff to devote more time and effort
      to the handling of problematic test results and contributing to improved patient
      care.

PMID- 28490182
TI  - Multiple myeloma and acquired von Willebrand disease: a combined cause of
      preanalytical interference causing gel formation?
AB  - We report a patient with acquired von Willebrand disease, associated with
      multiple myeloma. At one stage in his illness, we were unable to analyse a sample
      sent in a serum separator tube, due to the presence of a gel within the separated
      serum layer. We suggest this was due to anomalous position of the gel because of
      the density of the sample caused by its high total protein concentration,
      exacerbated by fibrin strand formation because of inhibition of appropriate
      fibrin clot formation secondary to clotting disorder.

PMID- 28490183
TI  - Clinical utility of measuring both glutamic acid decarboxylase antibodies and
      islet cell antibodies in the diagnosis of latent autoimmune diabetes in adults -
      is it cost-effective?

PMID- 28490184
TI  - Electrophoretic patterns post daratumumab.
AB  - Background Daratumumab (Darzalex) is a human IgG1 kappa monoclonal antibody
      targeting CD38 that has been recently approved for the treatment of refractory
      multiple myeloma. As it is a monoclonal protein, it can be detected on routine
      serum protein electrophoresis and by immunofixation. Methods Serum samples from
      four patients were analysed by serum protein electrophoresis immediately pre- and
      post-treatment with daratumumab. Results For all four patients, daratumumab was
      visible on serum protein electrophoresis as an additional small band
      (approximately 1 g/L) in the slow gamma region. Conclusion Diagnostic
      laboratories should be aware that daratumumab can be detected on routine serum
      protein electrophoresis of myeloma patients and should liaise closely with
      clinicians to ensure the presence of daratumumab is not misinterpreted as
      development of a new monoclonal protein.

PMID- 28490185
TI  - Low dehydroepiandrosterone sulphate: a sensitive and specific test for the
      detection of subclinical hypercortisolism in adrenal incidentalomas.

PMID- 28490186
TI  - Two-dimensional quantitative structure-activity relationship study of 1,4
      naphthoquinone derivatives tested against HL-60 human promyelocytic leukaemia
      cells.
AB  - A series of 50 derivatives of 1,4-naphthoquinone tested against human HL-60
      leukaemic cells showed activity at a wide range of concentrations. A multivariate
      quantitative structure-activity relationship (QSAR) study of 45 compounds was
      performed through principal component analysis (PCA) and partial least squares
      (PLS) regression. A good PLS regression model was obtained with two factors
      describing 60.1% of the total variance, and the selected descriptors were partial
      atomic charge at carbons 1 and 10 (C1 and C10) and total dipole moment (DIP). The
      calibration model exhibited the determination coefficient r2 = 0.78 and the
      standard error of calibration = 0.29. For external validation, r2 and the
      standard error of prediction were 0.74 and 0.32, respectively. DIP and C1 were
      the main descriptors for PCA, as well as for PLS, such that the pIC50 value
      increases when C1 increases and DIP diminishes. The selected descriptors are in
      accordance with the literature, once C10 and C1 are bound or close to the quinone
      oxygens involved in the production of radical anions (O2-?). From the QSAR
      analysis, the structures of two new naphthoquinones were proposed and their
      estimated IC50 values were 1.42 and 1.13 MUmol L-1.

PMID- 28490187
TI  - Episodic status migrainosus: One more case.

PMID- 28490188
TI  - The retinal microcirculation in migraine: The Rotterdam Study.
AB  - Background To explore the role of microvascular pathology in migraine, we
      investigated the association between migraine and retinal microvascular damage.
      Methods We included 3270 participants (age >= 45 years, 63% women) from the
      population-based Rotterdam Study (2006-2009). Participants with migraine were
      identified using a validated questionnaire based on ICHD-II criteria (n = 562).
      Retinopathy signs were graded on fundus photographs. Retinal arteriolar and
      venular caliber were measured by semi-automatic assessment of fundus photographs.
      Associations of migraine with retinopathy and retinal microvascular calibers were
      examined using logistic and linear regression models, respectively, adjusting for
      age, sex, and cardiovascular risk factors. Results Migraine was not associated
      with the presence of retinopathy (odds ratio (OR): 1.09, 95% confidence interval
      (CI) 0.62; 1.92). In the fully adjusted model, adjusting for the companion
      vessel, persons with migraine did not differ in retinal arteriolar or venular
      caliber compared to persons without migraine (mean difference in standardized
      arteriolar caliber -0.05 (95%CI -0.13; 0.03); in standardized venular caliber 
      0.00 (95%CI -0.09; 0.08)). Migraine subtypes, including migraine with aura, were
      also not associated with retinal microvascular damage. Conclusions Our findings
      suggest that migraine is not associated with retinopathy or difference in retinal
      microvascular caliber. Further studies are needed to confirm these results.

PMID- 28490189
TI  - Langerhans cell histiocytosis (eosinophilic granuloma) of the skull mimicking
      nummular headache. Report of two cases.
AB  - Background Nummular headache is a rare, recently described topographic headache
      defined by the circumscribed coin-shaped area of pain. It is classified as a
      primary headache. There is debate about whether it is due to a peripheral or
      central disturbance, and its relationship to migraine. Case reports We report two
      patients with presumed nummular headache secondary to Langerhans cell
      histiocytosis, both with resolution of their headaches after surgical resection.
      Conclusion Imaging in patients with clinical features of nummular headache is
      recommended, as this and other cases highlight that it may be symptomatic. There
      are no distinguishing clinical features to separate nummular headache from
      secondary mimics, and treatment of the underlying cause may be curative.

PMID- 28490190
TI  - Deployment-Related Traumatic Events and Suicidal Behaviours in a Nationally
      Representative Sample of Canadian Armed Forces Personnel.
AB  - OBJECTIVE: Worldwide, there has been substantial controversy with respect to
      whether military deployment is a risk factor for suicidal behaviour. The present
      study examined the relationship between lifetime exposure to deployment and
      deployment-related traumatic events (DRTEs) and past-year suicidal ideation (SI),
      suicidal plans (SP), and suicidal attempts (SA). METHOD: Data were analysed from
      the 2013 Canadian Forces Mental Health Survey (8161 respondents; response rate,
      79.8%; aged 18-60 years). A total of 12 individual items assessed exposure to
      DRTEs (e.g., combat, witnessing human atrocities, feeling responsible for the
      death of Canadian or ally personnel, knowing someone who was injured or killed).
      We examined each individual DRTE type as well as the number of types of DRTEs in
      relation to suicidal behaviour. RESULTS: Lifetime deployment was not
      significantly associated with suicidal behaviour. In models adjusted for
      sociodemographic variables, most of the individual DRTE items and the DRTE count
      variable were significantly associated with suicidal behaviours (adjusted odds
      ratio ranged between 1.10 and 5.32). When further adjusting for child abuse
      exposure, these associations were minimally attenuated, and some became
      nonsignificant. In models adjusting for mental disorders and child abuse, most
      DRTEs and number of types of DRTEs became nonsignificant in relation to SI, SP,
      and SA. CONCLUSIONS: Active military personnel exposed to increasing number of
      DRTEs are at increased risk for SI, SP, and SA. However, most of the association
      between DRTEs and suicidal behaviour is accounted for by child abuse exposure and
      mental disorders.

PMID- 28490191
TI  - Proliferative and antioxidant activity of Symphytum officinale root extract.
AB  - The root of Symphytum officinale L. is commonly used in folk medicine to promote
      the wound healing, reduce the inflammation and in the treatment of broken bones.
      The objective of our investigation was to analyse the extract from S. officinale
      in term of its antioxidant activity and the effect on cell viability and
      proliferation of human skin fibroblast (HSF). Moreover, the quantification of
      main phenolics and allantoin was conducted using HPLC-DAD method. Five compounds
      were found: rosmarinic, p-hydroxybenzoic, caffeic, chlorogenic and p-coumaric
      acid. DPPH, FRAP and TPC assay showed the high antioxidant activity of the
      extract. MTT test proved the stimulatory effect on cell metabolism and viability
      of HSF cells. Moreover, no changes in cytoskeleton structure and cells shape were
      observed. The obtained results indicate that non-toxic extract from S. officinale
      root has strong antioxidant potential and a beneficial effect on human skin
      fibroblasts.

PMID- 28490192
TI  - LTX-315: a first-in-class oncolytic peptide that reprograms the tumor
      microenvironment.
AB  - The oncolytic peptide LTX-315, which has been de novo designed based on structure
      activity relationship studies of host defense peptides, has the ability to kill
      human cancer cells and induce specific anticancer immune response when injected
      locally into tumors established in immunocompetent mice. The oncolytic effect of
      LTX-315 involves perturbation of plasma membrane and the mitochondria with
      subsequent release of danger-associated molecular pattern molecules, which
      highlights the ability of LTX-315 to induce complete regression and protective
      immune responses. Treatment with LTX-315 reprograms the tumor microenvironment by
      decreasing the local abundance of immunosuppressive cells and by increasing the
      frequency of effector T cells.

PMID- 28490193
TI  - Aminoisoquinoline benzamides, FLT3 and Src-family kinase inhibitors, potently
      inhibit proliferation of acute myeloid leukemia cell lines.
AB  - AIM: Mutated or overexpressed FLT3 drives about 30% of reported acute myeloid
      leukemia (AML). Currently, FLT3 inhibitors have shown durable clinical responses
      but a complete remission of AML with FLT3 inhibitors remains elusive due to
      mutation-driven resistance mechanisms. The development of FLT3 inhibitors that
      also target other downstream oncogenic kinases may combat the resistance
      mechanism. RESULTS: 4-substituted aminoisoquinoline benzamides potently inhibit
      Src-family kinases and FLT3, including secondary mutations, such as FLT3D835.
      Modifications of aminoisoquinoline benzamide to aminoquinoline or
      aminoquinazoline abrogated FLT3 and Src-family kinase binding. CONCLUSION: The
      lead aminoisoquinolines potently inhibited FLT3-driven AML cell lines, MV4-11 and
      MOLM-14. These aminoisoquinoline benzamides represent new kinase scaffolds with
      high potential to be translated into anticancer agents.

PMID- 28490194
TI  - Prepulse Inhibition of the Auditory Off-Response: A Magnetoencephalographic
      Study.
AB  - A weak preceding sound stimulus attenuates the startle response evoked by an
      intense sound stimulus. Like startle reflexes, change-related auditory responses
      are suppressed by a weak leading stimulus (ie, a prepulse). We aim to examine
      whether a prepulse inhibits cerebral responses to the sound offset and how the
      prepulse magnitude affects the degree of the prepulse inhibition (PPI). Using
      magnetoencephalography, we recorded the Off-P50m elicited by an offset of a train
      sound of 100-Hz clicks in 12 healthy subjects. A single click slightly louder
      (+1.5, +3, or +5 dB) than the background sound of 80 dB was inserted 50 ms before
      the sound offset as a prepulse. We performed a dipole source analysis of the Off
      P50m, and we measured its latency and amplitude using the source strength
      waveforms. The origin of the Off-P50m was estimated to be the auditory cortex on
      both hemispheres. The Off-P50m was clearly attenuated by the prepulses, and the
      degree of PPI was greater with a louder prepulse. The Off-P50m is considered to
      be a simple change-related response, which does not overlap with a processing of
      incoming sounds. Thus, the Off-P50m and its PPI comprise a valuable tool for
      investigating the neural inhibitory system.

PMID- 28490195
TI  - The Takei Handheld Dynamometer: An Effective Clinical Outcome Measure Tool for
      Hand and Wrist Function in Boxing.
AB  - BACKGROUND: The aim of this article was to explore retrospectively the Takei
      dynamometer as a valid and reliable outcome measure tool for hand and wrist
      pathology in the Great Britain amateur boxing squad between 2010 and 2014.
      METHODS: Longitudinal retrospective injury surveillance of the Great Britain
      boxing squad was performed from 2010 to 2014. The location, region affected,
      description, and duration of each injury were recorded by the team doctor and
      team physiotherapists. For each significant injury, we recorded hand grip scores
      using the Takei handheld dynamometer and compared the scores with baseline
      measures. RESULTS: At the hand, fractures and dislocations were highly detected
      with an average difference of 40.2% ( P < .05) when comparing postinjury to
      baseline measures. At the wrist, carpometacarpal and carpal joint injuries were
      highly detected with an average difference of 32.6% ( P < .05). Other injuries
      provided varied results. In the absence of pathology, up to 15% difference
      between left and right scores can be considered normal with a predominance
      observed below 10%. A difference of 20% can be indicative of a form of pathology,
      although pathologies can also be present with lower difference or no apparent
      changes. A difference of >20% should be highly considered for significant
      pathology. CONCLUSIONS: The Takei dynamometer is a valid and reliable outcome
      measure tool for hand and wrist pathologies in boxing. Our study highlights the
      importance of appropriate clinical tools to guide injury management in this
      sport.

PMID- 28490196
TI  - Effectiveness of second-line antiretroviral therapy: the impact of drug switches.
AB  - Including antiretroviral drug switches as a measure of ART failure could be more
      suitable than conventional measures to evaluate health outcomes in "real-world"
      settings. This is part of a historical cohort of HIV-infected adults who
      initiated ART from 2001-2005, and were followed up for a maximum of five years in
      three HIV/AIDS centers in Belo Horizonte, Brazil. Follow-up information included
      data from 2001-2010. All patients switched from first-line ART were included.
      Second-line ART effectiveness was measured as the time-to-ART failure. Failure
      was defined simulating two scenarios: (1) Clinical, immunological and virological
      failure (scenario 1); and scenario 1 plus ART switches (scenario 2). Descriptive
      analysis, Kaplan-Meier curves, log-rank test, and Cox proportional hazards model
      were performed. We identified 119 eligible patients; most had protease inhibitor
      (PI)-based regimens prescribed as second-line. The incidence of failure was
      different for the two scenarios (29.4% vs. 54.6% for scenario 1 and 2,
      respectively; p < 0.001). The main identifiers of failure were increase in viral
      load (31.1%) for scenario 1 and ART switches (42.8%) for scenario 2. Median
      duration on second-line ART was 36.8 vs. 19.8 months for scenario 1 and 2,
      respectively. In the Cox analysis of scenario 2, increased risk was found for
      patients given PI-based second-line regimens (HR = 2.26; 95% CI: 1.09-3.17).
      There is a high incidence of ART failure associated with PI-based regimens when
      ART switches are considered as an indicator of failure. This demonstrates the
      impact of ART switches in representing lack of ART effectiveness.

PMID- 28490197
TI  - Psychological and behavioral barriers to ART adherence among PLWH in China: role
      of self-efficacy.
AB  - Globally, optimal adherence to antiretroviral therapy (ART) is insufficient
      despite it is critical for maximum clinical benefits and treatment success among
      people living with HIV (PLWH). Many factors have been evidenced to influence
      medication adherence, including perceived barriers and self-efficacy. However,
      limited data are available regarding to psychological and behavioral barriers to
      ART adherence in China. Moreover, few studies have examined the mechanism of
      these two factors underlying HIV medication adherence. The aim of the current
      study is to examine the mediating role of adherence self-efficacy between
      perceived barriers and ART adherence among PLWH. Cross-sectional data were
      obtained from 2095 PLWH in Guangxi China who provided data on ART adherence.
      Participants reported their medication adherence, self-efficacy, barriers to ART
      adherence, as well as background characteristics. Results indicated a significant
      indirect effect from perceived barriers to medication adherence through adherence
      self-efficacy. Higher perceived psychological and behavioral barriers to ART
      adherence were related to lower adherence self-efficacy, which in turn was
      related to lower ART adherence. Self-efficacy could buffer the negative effects
      of perceived barriers on ART adherence. Future interventions to promote HIV
      medication adherence are recommended to focus on eliminating psychological and
      behavioral barriers, as well as increasing adherence self-efficacy.

PMID- 28490198
TI  - Drug-Induced Takotsubo Cardiomyopathy.
AB  - BACKGROUND: The most plausible hypothesis for takotsubo cardiomyopathy (TCM) is a
      catecholamine surge. Direct administration of catecholamines or medications
      causing catecholamine surge is frequently used in clinical practice. METHODS: A
      Medline/PubMed database search was conducted for case reports or series of drug
      induced TCM. All reported cases of drug-induced TCM were systemically identified
      and analyzed. RESULTS: We identified 157 cases of drug-induced TCM. Fifty-seven
      (36.3%) cases were related to the administration of exogenous catecholamines. In
      50 (31.9%) other cases, there was potential adrenergic effect. This included
      drugs with adrenergic vasoconstriction properties (3.2%), hyperadrenergic state
      due to alcohol or opioid withdrawal (7.7%), inhibitors of catecholamine reuptake
      (14.7%), anaphylactic reaction that is accompanied by catecholamine release
      (3.2%), and psychological or somatic stress coinciding with the administration of
      a drug that was thought to be the culprit (3.2%). Overall, 68.2% of these drug
      induced TCM cases were catecholamine related. In 14 (8.9%) cases, the likely
      etiology of cardiomyopathy was chemotherapy-induced coronary vasospasm.
      CONCLUSION: Our systematic review showed that over two-thirds of drug-induced TCM
      cases were due to direct or indirect catecholamine stimulation. The lowest
      effective dose and shortest duration of catecholamines should be utilized, and
      alternative therapies should be considered if feasible.

PMID- 28490199
TI  - Towards the Future Development of an Electrochemical Continuous Multimarker
      Biosensor for Enhanced Glycemic Management.

PMID- 28490201
TI  - A comparison of haemodynamics between subcranial-intracranial bypass and the
      traditional extracranial-intracranial bypass.
AB  - BACKGROUND: Ischemic cerebrovascular diseases are traditionally treated using an
      extracranial-intracranial (EC-IC) bypass. The use of the internal maxillary
      artery (IMA) in the subcranial-intracranial (SC-IC) bypass was recently described
      as an alternative treatment. However, the haemodynamics of this new approach have
      not been defined. METHODS: The haemodynamic parameters (flow volume [FV],
      internal diameter [ID], time-averaged mean velocity [TAM], pulsatility index [PI]
      and resistance index [RI]) of the IMA-radial artery graft (RAG)-middle cerebral
      artery (MCA) (n = 12) bypass and superficial temporal artery (STA)-MCA bypass (n
      = 18) were measured using intraoperative duplex ultrasonography and compared.
      RESULTS: The FV was 81.36 +/- 30.41 (62.05-100.70) ml/min for the IMA-RAG-MCA
      bypass. This was significantly higher than that of the STA-MCA bypass (27.25 +/-
      9.32 (22.62-31.88) ml/min; P < .01). The ID and TAM in the IMA-RAG-MCA bypass
      were higher than in the STA-MCA bypass (P < .01; P < .01). No significant
      differences were observed in PI (P ~ .21) and RI (P ~ .08). The early patency
      rate (one month after the operation) was 100% for the IMA-RAG-MCA bypass and 94%
      for the STA-MCA bypass. CONCLUSIONS: The IMA-RAG-MCA bypass provides moderate to
      high blood flow to the revascularized territory and blood flow was higher by this
      method than the STA-MCA bypass.

PMID- 28490200
TI  - Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by
      Adeno-Associated Virus Genomes.
AB  - Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of
      human airway epithelia. The packaging of a recombinant adeno-associated virus 2
      (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that
      also efficiently transduces human airway epithelia. As such, this vector is
      attractive for use in gene therapies to treat lung diseases such as cystic
      fibrosis. However, preclinical development of rAAV2/HBoV1 vectors has been
      hindered by the fact that humans are the only known host for HBoV1 infection.
      This study reports that rAAV2/HBoV1 vector is capable of efficiently transducing
      the lungs of both newborn (3- to 7-day-old) and juvenile (29-day-old) ferrets,
      predominantly in the distal airways. Analyses of in vivo, ex vivo, and in vitro
      models of the ferret proximal airway demonstrate that infection of this
      particular region is less effective than it is in humans. Studies of vector
      binding and endocytosis in polarized ferret proximal airway epithelial cultures
      revealed that a lack of effective vector endocytosis is the main cause of
      inefficient transduction in vitro. While transgene expression declined
      proportionally with growth of the ferrets following infection at 7 days of age,
      reinfection of ferrets with rAAV2/HBoV1 at 29 days gave rise to approximately 5
      fold higher levels of transduction than observed in naive infected 29-day-old
      animals. The findings presented here lay the foundation for clinical development
      of HBoV1 capsid-based vectors for lung gene therapy in cystic fibrosis using
      ferret models.

PMID- 28490202
TI  - Tumor necrosis factor inhibitors in psoriatic arthritis.
AB  - INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease that
      can result in significant disability. With the emergence of tumor necrosis factor
      inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The
      clinical efficacy and the inhibition of radiographic progression demonstrated by
      TNFi have transformed the management of PsA. However, there is still an unmet
      need for a subset of patients who do not respond adequately to TNFi. Areas
      covered: This review provides an overview of the pharmacokinetics of TNFi, the
      efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment
      of PsA. In addition, we address the use of TNFi in the setting of other
      medications utilized in the treatment of PsA and the potential future role of
      biosimilars. Expert commentary: Monoclonal antibodies exhibit complex and widely
      variable pharmacokinetics. The study of factors that can affect the
      pharmacokinetics, such as immunogenicity, is valuable to further define and
      understand the use of TNFi in PsA, especially in the subset of patients who do
      not respond adequately to these agents or lose effectiveness over time.

PMID- 28490203
TI  - C-SAFE: A Computer-Delivered Sexual Health Promotion Program for Latinas.
AB  - This article describes the development and evaluation of C-SAFE (Sexual Awareness
      for Everyone), a computer-delivered sexual health promotion program for Latinas.
      We first describe the process of adapting an evidence-based, group-level
      intervention into an individually administered computer-delivered program. We
      then present the methods and results of a randomized control trial with 321
      Latinas in California and Florida to test C-SAFE's preliminary efficacy in
      reducing sexual health risk. We found no statistically significant differences
      between the two conditions at a six-month follow-up in terms of sexual behaviors
      or attitudes toward sexually transmitted infections and condoms, although C-SAFE
      women reported fewer days in the past month when their mental health was not good
      (p = .02). C-SAFE condition women also reported more satisfaction than control
      condition women in their assessment of information presentation (on a scale of 1
      = poor and 5 = excellent; C-SAFE = 4.45 vs. control = 4.25, p = .053) and having
      learned something new (C-SAFE = 95.1% vs. control = 79.3%, chi2 < 0.001), with
      utility of content for Latinas approaching significance (C-SAFE = 4.50 vs.
      control = 4.31, p = .058). In conclusion we discuss the importance of teachable
      moments, matching of delivery modalities to implementation contexts, and possible
      directions for evidence-based sexual health promotion programs given the current
      sexual health landscape.

PMID- 28490204
TI  - Exploring participatory behaviour of disability benefit claimants from an
      insurance physician's perspective.
AB  - PURPOSE: In the Dutch social security system, insurance physicians (IPs) assess
      participatory behaviour as part of the overall disability claim assessment. This
      study aims to explore the views and opinions of IPs regarding participatory
      behaviour as well as factors related to inadequate participatory behaviour, and
      to incorporate these factors in the International Classification of Functioning,
      Disability and Health (ICF) biopsychosocial framework. METHOD: This qualitative
      study collected data by means of open-ended questions in 10 meetings of local
      peer review groups (PRGs) which included a total of 78 IPs of the Dutch Social
      Security Institute. In addition, a concluding discussion meeting with 8 IPs was
      organized. RESULTS: After qualitative data analyses, four major themes emerged:
      (1) participation as an outcome, (2) efforts of disability benefit claimants in
      the process of participatory behaviour, (3) beliefs of disability benefit
      claimants concerning participation, and (4) recovery behaviour. Identified
      factors of inadequate participatory behaviour covered all ICF domains, including
      activities, environmental, and personal factors, next to factors related to
      health condition and body functions or structures. Outcomes of the discussion
      meeting indicated the impossibility of formulating general applicable criteria
      for quantifying and qualifying participatory behaviour. CONCLUSIONS: Views of IPs
      on disability benefit claimants' (in)adequate participatory behaviour reflect a
      broad biopsychosocial perspective. IPs adopt a nuanced tailor-made approach
      during assessment of individual disability benefit claimants' participatory
      behaviour and related expected activities aimed at recovery of health and RTW.
      Implications for Rehabilitation Within a biopsychosocial perspective, it is not
      possible to formulate general criteria for the assessment of participatory
      behaviour for each unique case. Individual disability benefit claimant
      characteristics and circumstances are taken into account. To optimize the return
      to-work (RTW) process, insurance physicians (IPs) assess participatory behaviour
      according to the International Classification of Functioning, Disability and
      Health, including medical, personal, and environmental factors. Some aspects
      within the concept of participatory behaviour extend beyond the boundaries of the
      domain where IPs operate because opinions in society on personal and societal
      responsibility influence participatory behaviour.

PMID- 28490205
TI  - Frequency and evaluation of the perceptions towards caesarean section among
      pregnant women attending public hospitals in Pakistan and the implications.
AB  - OBJECTIVES: There is increasing prevalence of caesarean sections (CS) worldwide;
      however, there are concerns about their rates in some countries, including
      potential fears among mothers. Consequently, we aimed to determine the frequency
      of CS, and explore patient's perception towards CS attending public hospitals in
      Pakistan, to provide future guidance. METHODS: A two-phased study design
      (retrospective and cross sectional) was adopted. A retrospective study was
      conducted to assess the frequency of CS over one year among four public
      hospitals. A cross sectional study was subsequently conducted to determine
      patients' perception towards CS attending the four tertiary care public hospitals
      in Quetta city, Pakistan, which is where most births take place. RESULTS: Overall
      prevalence of CS was 13.1% across the four hospitals. 728 patients were
      approached and 717 responded to the survey. Although 78.8% perceived CS as
      dangerous, influenced by education (p = 0.004), locality (p = 0.001) and
      employment status (p = 0.001), 74.5% of patients were in agreement that this is
      the best approach to save mother's and baby's lives if needed. 62% of respondents
      reported they would like to avoid CS if they could due to post-operative pain,
      and 58.9% preferred a normal delivery. There was also a significant association
      with education (p = 0.001) and locality (p = 0.001) where respondents considered
      normal vaginal delivery as painful. CONCLUSION: The overall frequency of CS
      approximates to WHO recommendations, although there is appreciable variation
      among the four hospitals. When it comes to perception towards CS, women had
      limited information. There is a need to provide mothers with education during the
      antenatal period, especially those with limited education, to accept CS where
      needed.

PMID- 28490206
TI  - Pharmacokinetics, pharmacodynamics and pharmacogenetics associated with
      nonsteroidal anti-inflammatory drugs and opioids in pediatric cancer patients.
AB  - INTRODUCTION: Advancing appropriate and adequate analgesic pharmacotherapy in
      pediatric patients with cancer is an area of clinical need. Few studies have been
      performed to evaluate the selection of an analgesic and appropriate dosing
      corresponding to analgesic effect among pediatric cancer patients. This review
      describes information related to pharmacokinetic, pharmacodynamic, and
      pharmacogenomic (when applicable) considerations for analgesics that are commonly
      used to manage pain experienced by pediatric patients with cancer. Areas covered:
      Analgesics commonly used to treat pediatric patients with malignancy patterned
      after the World Health Organization's 'analgesic ladder' for cancer pain
      management. Expert opinion: Addressing pain management safely and effectively in
      pediatric patients with cancer will require advances in both drug development, to
      increase the armament of analgesics available for children, and our pharmacologic
      understanding of those analgesics in current use. However, performing the
      necessary types of studies to develop new analgesics, or gain knowledge of
      existing therapy, within a population that is relatively small, diverse, and who
      experience pain originating from a variety of sources, is a tremendous challenge.

PMID- 28490207
TI  - microRNA-124: a putative therapeutic target and biomarker for major depression.

PMID- 28490208
TI  - Plasma kisspeptin levels in lactational amenorrhea.
AB  - The kisspeptin is a neuropeptide to play physiological roles in regulating
      gonadotropin-releasing hormone secretion in the hypothalamus. In human plasma,
      the kisspeptin concentration is measured, but gonadotropin-releasing hormone is
      not. This study aims to understand the physiological roles of the circulating
      kisspeptin in lactational amenorrhea in humans because prolactin reduces the
      kisspeptin expression and luteinizing hormone secretion resulting in anovulations
      in rodent brains. Plasma kisspeptin levels were measured in 11 subjects in
      lactational amenorrhea and in four cases with pathological amenorrhea by
      different etiologies for comparison using the enzyme immunoassay specific for
      human kisspeptin. The plasma kisspeptin levels in the 11 women with lactational
      amenorrhea were 15.2 +/- 2.5 fmol/mL (mean +/- SD) which were not significantly
      different as compared with 16.5 +/- 4.8 fmol/mL (mean +/- SD) in four age-matched
      women with menstrual cycles as we reported previously. In the four cases with
      pathological amenorrhea, their plasma kisspeptin levels were from 5.8 to 13.7
      fmol/mL. This study demonstrated that the plasma kisspeptin levels were not
      totally reduced in lactational or pathological amenorrhea. These results suggest
      the physiological roles of the circulating kisspeptin are different from the role
      in the brain.

PMID- 28490209
TI  - Retrospective analysis in 46 women with vulvovaginal atrophy treated with
      ospemifene for 12 weeks: improvement in overactive bladder symptoms.
AB  - AIMS: The aim of this study was to assess the effectiveness and safety of
      ospemifene in the improvement of overactive bladder (OAB) symptoms in
      postmenopausal women affected by vulvovaginal atrophy (VVA). METHODS: Forty-six
      postmenopausal patients affected by VVA with OAB syndrome were enrolled for the
      study. All patients received Ospemifene 60 mg for 12 weeks. Clinical examination,
      3-day voiding diary, urodynamic testing, ultrasound measurement of endometrial
      and bladder wall thickness (BWT) and the Vaginal Health Index (VHI) were
      performed at baseline and 12 weeks. Patients completed the OAB-Q SF and UDI-6.
      RESULTS: After 12-weeks, the number of patients with detrusor overactivity
      decreased from 39% to 13% (p = 0.04). The reduction in the mean number in 24 h of
      voids (9.57 +/- 2.12 vs. 6.63 +/- 1.22, p < 0.0001), urgent micturition
      episodes/24 h (5.63 +/- 1.46 vs. 1.44 +/- 1.31, p < 0.0001), nocturia episodes
      (3.17 +/- 0.85 vs. 1.11 +/- 1.18, p < 0.0001), urinary incontinence episodes/24 h
      (0.85 +/- 0.96 vs. 0.33 +/- 0.64, p = 0.003) was observed. The UDI-6, OAB-Q
      symptoms, OAB-Q (HRQL) scores were 8.95 +/- 0.91 vs. 5.56 +/- 1.40, 62.60 +/-
      14.70 vs. 20.08 +/- 10.83 and 18.71 +/- 7.41 vs. 79.45 +/- 14.47 (p < 0.001)
      before and after 12 weeks. CONCLUSION: Ospemifene is an effective potential
      therapy for postmenopausal women with VVA improving OAB symptoms and quality of
      life.

PMID- 28490210
TI  - ADHD Symptoms and Quality of Life Across a 12-Month Period in Children With ADHD:
      A Longitudinal Study.
AB  - OBJECTIVE: To describe the relationship between ADHD symptom severity and quality
      of life (QoL) across three time points over a 12-month period and investigate
      whether sleep modifies this relationship. METHOD: Children aged 5 to 13 years
      with ADHD were recruited from 21 pediatric practices across Victoria, Australia (
      N = 392). Child QoL (parent-report) and ADHD symptoms (both parent- and teacher
      report) were assessed at three time points (0, 6, and 12 months), and sleep was
      assessed at baseline (parent-report). Data were analyzed using Pearson's
      correlations and autoregressive cross-lagged panel models. RESULTS: Parent
      reported ADHD symptoms predicted poorer QoL at each subsequent time point ( r = 
      .10 to -.13), and a small bidirectional relationship was observed between teacher
      reported ADHD symptoms and QoL from 6 to 12 months. Sleep moderated the
      relationship between ADHD symptoms and QoL. CONCLUSION: Clinicians need to look
      beyond core ADHD symptoms to other factors that may be influencing QoL in
      children with ADHD.

PMID- 28490212
TI  - Effects of ADHD on Writing Composition Product and Process in School-Age
      Students.
AB  - OBJECTIVE: This study examined the relationship between ADHD and writing
      performance. METHOD: Students in Grades 3 to 7, 84 with ADHD and 135 age- and
      gender-matched controls completed a writing task (including process logs), and
      measures of working memory and attention. RESULTS: Students with ADHD wrote texts
      of similar length but with poorer structure, coherence, and ideation. In all,
      6.7% of the variance in writing quality was explained by whether or not the
      student had an ADHD diagnosis, after control for IQ and age-within-year, with
      ADHD students producing text that was less coherent, well structured, and
      ideationally rich, and spending less time thinking about and reviewing their
      text. Half of the effect on text quality could be attributed to working memory
      and sustained attention effects. CONCLUSION: ADHD has some effect on writing
      performance, which can, in part, be explained by working memory and attentional
      deficits.

PMID- 28490213
TI  - Are fluorescence-based chlorophyll quantification methods suitable for algae
      toxicity assessment of carbon nanomaterials?
AB  - Using a multiwalled carbon nanotube (MWCNT) and graphene oxide (GO) as
      representative test materials, we evaluated the applicability of in vivo and in
      vitro chlorophyll-a (Chl-a) fluorescence quantification methods, which are used
      in standard algae ecotoxicity tests such as OECD 201 and ISO 8692. In vivo
      quantification of Chl-a from Raphidocelis subcapitata indicated a significant
      reduction in Chl-a fluorescence in the presence of MWCNTs due to shading, but a
      significant autofluorescence from GO caused an overestimation of Chl-a
      concentration. In vitro Chl-a quantification methods employing a modified acetone
      and an ethanol extraction protocol reduced the influence of shading and
      autofluorescence, but both resulted in a significant loss of fluorescence signal
      in the presence of 100 mgL-1 MWCNTs (99-100%) and GO (21-52%). Chl-a reduction
      was dose dependent for both tested carbon-based MNMs (CNMs), but effects were
      more pronounced for MWCNT, which caused a significant fluorescence reduction (16
      +/- 0.3%) already at 1 mgL-1. Further study of the CNM-algae-Chl-a interaction
      processes revealed that CNM can not only interact with live algae, but also
      efficiently adsorb extracted Chl-a. Our results showed that within 10 min, 95
      100% of Chl-a extracted from two algae concentrations were adsorbed to MWCNT,
      while 35-60% of Chl-a was adsorbed to the GO. This study shows that Chl-a
      quantification by fluorescence determination is not a suitable method for
      ecotoxicity testing of CNM. However, a quick screening test for individual MNMs
      is recommended to determine whether Chl-a adsorption is a significant process
      prior to selection of a quantification method.

PMID- 28490214
TI  - Emerging amyloid and tau targeting treatments for Alzheimer's disease.
AB  - INTRODUCTION: With an ageing global population, the number of people with
      dementia, and its main cause Alzheimer's disease (AD), is growing. current
      licensed treatments available for ad are only alleviate the symptoms of the
      disease, and are effective only in some people with ad for a limited time. there
      are currently no therapies that target the disease process. Areas covered: This
      review summarizes the available treatments for AD and the emerging therapies in
      the clinical trials pipeline. There are ongoing trials at various stages of
      development, targeting different mechanisms and pathways implicated in the
      disease. This review focuses on amyloid and tau targeting drug candidates. Expert
      commentary: Despite research efforts targeted at understanding AD, the underlying
      mechanisms and optimal treatment targets have not been fully elucidated. There is
      a significant need for further research targeting the disease at an earlier stage
      and progress in biomarker and imaging technology are improving the outlook. It is
      critical to continue research into identifying the underlying pathology and
      disease process in Alzheimer's disease to enable development of effective
      targeted treatments.

PMID- 28490215
TI  - The safety of daratumumab for the treatment of multiple myeloma.
AB  - INTRODUCTION: The overall survival of patients with multiple myeloma (MM) has
      changed dramatically in the last decade. MM remains an incurable plasma cell
      disorder but immunotherapy with monoclonal antibodies (MoAbs) has emerged as a
      promising treatment. Areas covered: Fully published, clinical trials including
      patients with relapsed or refractory MM were reviewed. Safety data of daratumumab
      (DARA) single-agent or in combination regimens have been addressed. Additionally,
      infusion-related reactions, data on special populations, and DARA-interference
      with laboratory testing, including assessment of MM response in patients have
      also been addressed. Expert opinion: Daratumumab both as single agent and in
      combination regimens has shown a favorable safety profile without significant
      increase in toxicities. Extensive clinical development of DARA is currently
      ongoing and given the efficacy that has been seen with this drug in clinical
      trials, DARA is likely to change the landscape of myeloma treatment.

PMID- 28490216
TI  - Prevalence and Psychosocial Correlates of ADHD Symptoms in Young Adulthood: A
      French Population-Based Study.
AB  - OBJECTIVE: The scientific literature suggests that ADHD in adulthood is
      associated with a considerable psychosocial burden. However, most knowledge in
      this area relies on studies conducted in the United States or in North European
      nations, thereby limiting generalization to other countries. METHOD: We assessed
      the psychosocial correlates of ADHD symptoms in a French community-based sample.
      Data came from 1,214 community-based young adults (18-35 years) and their parents
      (Trajectoires Epidemiologiques en Population and GAZEL studies). ADHD symptoms
      and socioeconomic and psychosocial correlates were assessed in a telephone
      interview. Logistic regression analyses were conducted to assess associations.
      RESULTS: A total of 7.1% of the sample presented high levels of ADHD symptoms.
      Parental history of anxiety, dissatisfaction with love life, and consumption of
      tobacco were associated with the highest odds ratios. CONCLUSION: This study
      confirms the high functional impairment associated with adult ADHD symptoms in a
      French community sample. It extends the existing literature to family risk
      correlates and individual well-being correlates.

PMID- 28490211
TI  - Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes?
AB  - The infusion of healthy stem cells into a patient-termed "stem-cell therapy"-has
      shown great promise for the treatment of genetic and non-genetic diseases,
      including mucopolysaccharidosis type 1, Parkinson's disease, multiple sclerosis,
      numerous immunodeficiency disorders, and aplastic anemia. Stem cells for cell
      therapy can be collected from the patient (autologous) or collected from another
      "healthy" individual (allogeneic). The use of allogenic stem cells is accompanied
      with the potentially fatal risk that the transplanted donor T cells will reject
      the patient's cells-a process termed "graft-versus-host disease." Therefore, the
      use of autologous stem cells is preferred, at least from the immunological
      perspective. However, an obvious drawback is that inherently as "self," they
      contain the disease mutation. As such, autologous cells for use in cell therapies
      often require genetic "correction" (i.e., gene addition or editing) prior to cell
      infusion and therefore the requirement for some form of nucleic acid delivery,
      which sets the stage for the AAV controversy discussed herein. Despite being the
      most clinically applied gene delivery context to date, unlike other more
      concerning integrating and non-integrating vectors such as retroviruses and
      adenovirus, those based on adeno-associated virus (AAV) have not been employed in
      the clinic. Furthermore, published data regarding AAV vector transduction of stem
      cells are inconsistent in regards to vector transduction efficiency, while the
      pendulum swings far in the other direction with demonstrations of AAV vector
      induced toxicity in undifferentiated cells. The variation present in the
      literature examining the transduction efficiency of AAV vectors in stem cells may
      be due to numerous factors, including inconsistencies in stem-cell collection,
      cell culture, vector preparation, and/or transduction conditions. This review
      summarizes the controversy surrounding AAV vector transduction of stem cells,
      hopefully setting the stage for future elucidation and eventual therapeutic
      applications.

PMID- 28490217
TI  - Antimicrobial proteins in the response to graphene oxide in Caenorhabditis
      elegans.
AB  - Upon exposure to environmental engineered nanomaterials (ENMs), animals will
      activate certain response signals to protect themselves from the toxic effects.
      However, the underlying molecular mechanisms for this response are still largely
      unclear. Using in vivo assay system of Caenorhabditis elegans, we here found that
      antimicrobial proteins of LYS-1, LYS-8, SPP-1, DOD-6, and F55G11.4 were activated
      by graphene oxide (GO) exposure. These antimicrobial proteins functioned as
      molecular targets of transcriptional factor DAF-16 in insulin signaling pathway,
      and acted in intestine to regulate the response to GO. Among these antimicrobial
      proteins, DOD-6, F55G11.4, and SPP-1 participated in the formation of signaling
      cascade of DAF-16-DOD-6-SOD-3-F55G11.4/SPP-1 in response to GO exposure by
      activating the antioxidation system. Different from this, LYS-1 and LYS-8, two
      lysozymes, mediated TUB-2 signaling and DAF-8-DAF-5 signaling cascade,
      respectively, to regulate the response to GO exposure. During the regulation of
      response to GO exposure, LYS-1 and LYS-8 acted synergistically, which could be
      largely explained by the observed synergistic interaction between TUB-2 and DAF
      8. Therefore, our results demonstrate the crucial protection role of
      antimicrobial proteins for animals in response to environmental ENMs' exposure.
      The elucidated different signaling cascades mediated by antimicrobial proteins
      provide important molecular targets for future toxicity assessment and chemical
      modification of GO.

PMID- 28490218
TI  - Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5
      antibody-positive dermatomyositis patients.
AB  - OBJECTIVES: We retrospectively investigated clinical prognostic factors for
      interstitial pneumonia (IP) in anti-melanoma differentiation-associated gene 5
      (MDA5) antibody (Ab)-positive dermatomyositis (DM) patients. METHODS: Subjects
      comprised 18 patients with anti-MDA5 Ab-positive DM-IP (9 survivors; 9 deaths).
      RESULTS: Initial serum albumin levels, ferritin levels, and ground-glass opacity
      (GGO) scores in the right middle lobes were significantly higher in the death
      group than in the survivor group (p = .033, .013, and .005, respectively).
      Initial alveolar-arterial oxygen gradient (P[A-a]O2) was also higher in the death
      group than in the survivor group (p = .064). Initial serum ferritin, P[A-a]O2,
      and right middle lobe GGO score were found to significantly relate to death.
      Survival rates after 24 weeks were significantly lower among patients with an
      initial ferritin level of >=450 ng/mL (25%), P[A-a]O2 of >=30 mmHg (31%), and a
      right middle lobe GGO score of >=2 (11%) than each of the others (p = .006, .020,
      and .002, respectively). CONCLUSIONS: An initial serum ferritin level of >=450
      ng/mL, P[A-a]O2 of >=30 mmHg, and right middle lobe GGO score of >=2 (GGO >=5% of
      the lobe) were identified as poor prognostic factors for anti-MDA5 Ab-positive DM
      IP patients.

PMID- 28490220
TI  - Solithromycin (CEM-101): A New Fluoroketolide Antibiotic and Its Role in the
      Treatment of Gonorrhea.
AB  - Solithromycin is a macrolide antibiotic that has undergone review for the
      treatment of community-acquired bacterial pneumonia. Solithromycin is also being
      investigated and has shown promise for the treatment of gonorrhea. With
      increasing antibiotic resistance, the development of novel antibiotics to combat
      infections is essential. The unique ribosome-binding stability of solithromycin
      and mild side effect profile make this a promising new antibiotic. This article
      will provide an overview on the mechanism of action, clinical efficacy, and
      safety of this drug for the treatment of gonorrhea. Relevant data were identified
      through a comprehensive literature search using multiple databases using the
      keywords solithromycin, CEM-101, and gonorrhea.

PMID- 28490221
TI  - Natural Health Products and Community Pharmacy-Remove the Mysticism Not the
      Product.
AB  - The allure of natural products has captivated humans for centuries. Although they
      can be compatible with evidence-based care, attitudes surrounding natural
      products can seem almost mystical and may even be accompanied by contempt toward
      Western medicine. Considering the high volumes of natural products sold in
      community pharmacies, pharmacists can inject balanced information to minimize the
      mysticism and help patients make informed decisions. The aim of this article is
      to argue for standardized guidelines pertaining to the management of natural
      products in community pharmacy practice.

PMID- 28490222
TI  - Inattention and Hyperactivity-Impulsivity: Their Detrimental Effect on Romantic
      Relationship Maintenance.
AB  - OBJECTIVE: The aim of this study is to understand how ADHD symptoms correlate
      with romantic relationship maintenance and test theoretical pathways by which
      symptoms of ADHD lead to relationship difficulties. METHOD: This study involved
      two phases of data collection, which were identical except for the population.
      Phase 1 ( n = 172) was a nonclinical sample of romantically involved young
      adults. Phase 2 ( n = 39) was a clinical sample of romantically involved young
      adults with ADHD. Participants in both phases reported on their levels of
      inattention and hyperactivity-impulsivity, their relationship maintenance
      activities, and their relationship quality. RESULTS: ADHD symptoms were
      associated with greater relationship difficulties. In both samples, inattentive
      symptoms were associated with greater interest in relational alternatives and
      less constructive responses to partner's bad behaviors, whereas hyperactive
      impulsive symptoms were associated with negative responses to bad behavior.
      CONCLUSION: The results of this study have implications for developing cognitive
      behavioral therapy interventions targeting relationship difficulties in young
      adults with ADHD.

PMID- 28490219
TI  - Recruitment of macrophages from the spleen contributes to myocardial fibrosis and
      hypertension induced by angiotensin II.
AB  - INTRODUCTION: The purpose of this study was to determine whether macrophages
      migrated from the spleen are associated with angiotensin II-induced cardiac
      fibrosis and hypertension. METHODS: Sprague-Dawley rats were subjected to
      angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In
      splenectomy, the spleen was removed before angiotensin II infusion. In the
      angiotensin II AT1 receptor blockade, telmisartan was administered by gastric
      gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were
      isolated for Western blot analysis and immunohistochemistry. RESULTS: Angiotensin
      II infusion caused a significant reduction in the number of monocytes in the
      spleen through the AT1 receptor-activated monocyte chemoattractant protein-1.
      Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively
      reduced the recruitment of macrophages into the heart. Associated with this
      change, transforming growth factor beta1 expression and myofibroblast
      proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated.
      Furthermore, interstitial/perivascular fibrosis was attenuated. These
      modifications occurred in coincidence with reduced blood pressure. At week 4,
      invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated
      and expression of endothelial nitric oxide synthase was upregulated, along with a
      reduction in aortic fibrosis. CONCLUSIONS: These results suggest that macrophages
      when recruited into the heart and aorta from the spleen potentially contribute to
      angiotensin II-induced cardiac fibrosis and hypertension.

PMID- 28490223
TI  - Molecular remodeling of the renin-angiotensin system after kidney
      transplantation.
AB  - OBJECTIVE: We aimed at assessing the molecular adaptation of the renin
      angiotensin system (RAS) after successful kidney transplantation (KTX). MATERIALS
      AND METHODS: In this prospective, exploratory study we analyzed 12 hemodialysis
      (HD) patients, who received a KTX and had excellent graft function six to 12
      months thereafter. The concentrations of plasma Angiotensin (Ang) peptides (Ang
      I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)) were simultaneously
      quantified with a novel mass spectrometry-based method. Further, renin and
      aldosterone concentrations were determined by standard immunoassays. RESULTS: Ang
      values showed a strong inter-individual variability among HD patients. Yet,
      despite a continued broad dispersion of Ang values after KTX, a substantial
      improvement of the renin/Ang II correlation was observed in patients without RAS
      blockade or on angiotensin receptor blocker (HD: renin/Ang II R2 = 0.660, KTX:
      renin/Ang II R2 = 0.918). Ang-(1-7) representing the alternative RAS axis was
      only marginally detectable both on HD and after KTX. CONCLUSIONS: Following KTX,
      renin-dependent Ang II formation adapts in non-ACE inhibitor-treated patients.
      Thus, a largely normal RAS regulation is reconstituted after successful KTX.
      However, individual Ang concentration variations and a lack of potentially
      beneficial alternative peptides after KTX call for individualized treatment. The
      long-term post-transplant RAS regulation remains to be determined.

PMID- 28490224
TI  - Prevalence of Abnormal Magnetic Resonance Imaging Findings in Children with
      Persistent Symptoms after Pediatric Sports-Related Concussion.
AB  - A subset of patients experience persistent symptoms after pediatric concussion,
      and magnetic resonance imaging (MRI) is commonly used to evaluate for pathology.
      The utility of this practice is unclear. We conducted a retrospective cohort
      study to describe the MRI findings in children with concussion. A registry of all
      patients seen at our institution from January 2010 through March 2016 with
      pediatric sports-related concussion was cross-referenced with a database of
      radiographical studies. Radiology reports were reviewed for abnormal findings.
      Patients with abnormal computed tomographies or MRI scans ordered for reasons
      other than concussion were excluded. Among 3338 children identified with
      concussion, 427 underwent MRI. Only 2 (0.5%) had findings compatible with
      traumatic injury, consisting in both of microhemorrhage. Sixty-one patients
      (14.3%) had abnormal findings unrelated to trauma, including 24 nonspecific T2
      changes, 15 pineal cysts, eight Chiari I malformations, and five arachnoid cysts.
      One child underwent craniotomy for a cerebellar hemangioblastoma after presenting
      with ataxia; another had cortical dysplasia resected after seizure. The 2
      patients with microhemorrhage each had three previous concussions, significantly
      more than patients whose scans were normal (median, 1) or abnormal without injury
      (median, 1.5; p = 0.048). MRI rarely revealed intracranial injuries in children
      post-concussion, and the clinical relevance of these uncommon findings remains
      unclear. Abnormalities unrelated to trauma are usually benign. However, MRI
      should be thoughtfully considered in children who present with concerning or
      atypical symptoms.

PMID- 28490225
TI  - Is a short arm cast appropriate for stable distal radius fractures in patients
      older than 55 years? A randomized prospective multicentre study.
AB  - : We conducted a prospective randomized, multicentre study to compare short arm
      and long arm plaster casts for the treatment of stable distal radius fracture in
      patients older than 55 years. We randomly assigned patients over the age of 55
      years who had stable distal radius fracture to either a short arm or long arm
      plaster cast at the first review 1 week after their injury. Radiographic and
      clinical follow-up was conducted at 1, 3, 5, 12 and 24 weeks following their
      injury. Also, degree of disability caused by each cast immobilization was
      evaluated at the patient's visit to remove the cast. There were no significant
      differences in radiological parameters between the groups except for volar tilt.
      Despite these differences in volar tilt, neither functional status as measured by
      the Disabilities of the Arm, Shoulder and Hand, nor visual analogue scale was
      significantly different between the groups. However, the mean score of disability
      caused by plaster cast immobilization and the incidence rate of shoulder pain
      were significantly higher in patients who had a long plaster cast. Our findings
      suggest that a short arm cast is as effective as a long arm cast for stable
      distal radius fractures in the elderly. Furthermore, it is more comfortable and
      introduces less restriction on daily activities. LEVEL OF EVIDENCE: II.

PMID- 28490227
TI  - Utilization of Continuous "Spinners" to Communicate Risk.
AB  - BACKGROUND: As patients become more involved in their medical care, they must
      consider the specific probabilities of both positive and negative outcomes
      associated with different treatments. Patients who are low in numeracy may be at
      a disadvantage when making these decisions. This study examined the use of a
      "spinner" to present probabilistic information compared to a numerical format and
      icon array. DESIGN: Subjects ( n = 151) were asked to imagine they suffered from
      chronic back pain. Two equally effective medications, each with a different
      incidence of rare and common side effects, were described. Subjects were
      randomized to 1 of 3 risk presentation formats: numeric only, numeric with icon
      arrays, or numeric with spinners, and answered questions regarding their risk
      knowledge, medication preference, and how much they liked the presentation
      format. RESULTS: Compared with the numeric only format, both the spinner and icon
      array increased risk knowledge and were rated more likeable by subjects. Subjects
      viewing the spinner format were also more likely to prefer the pill with the
      lowest side-effect burden. LIMITATIONS: The relatively small size, convenience
      sample, and hypothetical scenario were limitations of this study. CONCLUSIONS:
      The use of continuous spinners presents a new approach for communicating risk to
      patients that may aid in their decision making.

PMID- 28490226
TI  - Intensity of hydration changes the role of renin-angiotensin-aldosterone system
      blockers in contrast-induced nephropathy risk after coronary catheterisation in
      patients with chronic kidney disease.
AB  - OBJECTIVE: This study evaluated the potential effect of hydration intensity on
      the role of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin
      receptor blockers (ARBs) on contrast-induced nephropathy in patients with renal
      insufficiency. METHODS: All eligible patients were included and stratified
      according to hydration intensity defined as saline hydration volume to body
      weight tertiles: <10.21 mL/kg, 10.21 to <17.86 mL/kg, and ?17.86 mL/kg. RESULTS:
      In total, 84 (6.7%) of 1254 patients developed contrast-induced nephropathy: 6.2%
      in the ACEI/ARB group versus 10.8% in the non-ACEI/ARB group ( P=0.029), with an
      adjusted odds ratio (OR) of 0.89 (95% confidence interval (CI) 0.46-1.73,
      P=0.735). The incidence of contrast-induced nephropathy was lower in the ACEI/ARB
      group than in the non-ACEI/ARB group in the second tertile ( P=0.031), while not
      significantly different in the first ( P=0.701) and third ( P=0.254) tertiles.
      ACEIs/ARBs were independently associated with a lower contrast-induced
      nephropathy risk (OR 0.26, 95% CI 0.09-0.74, P=0.012) and long-term all-cause
      death (hazard ratio 0.461, 95% CI 0.282-0.755, P=0.002) only in the second
      hydration volume to body weight tertile. CONCLUSION: The effects of ACEIs/ARBs on
      contrast-induced nephropathy risk vary according to saline hydration intensity in
      chronic kidney disease patients, and may further reduce contrast-induced
      nephropathy risk in patients administered moderate saline hydration.

PMID- 28490228
TI  - Concussion Mechanisms and Activities in Youth, High School, and College Football.
AB  - Our purpose was to determine concussion mechanism and activity differences among
      three cohorts of football players: youth, high school, and college. Participants
      in this prospective cohort study were youth (ages 5-14 years, 118 teams, 310 team
      seasons), high school (96 teams, 184 team-seasons), and college (34 teams, 71
      team-seasons) football players. Athletic trainers collected athlete-exposure (AE)
      and concussion data during the 2012-2014 seasons. Injury mechanism referred to
      the object that made contact with the concussed player, resulting in the
      concussion. Injury activity referred to the type of football-specific activity
      that the player was involved in when the concussion was sustained. Injury
      proportion ratios (IPR) compared distributions of concussion mechanisms and
      activities among age levels. A total of 1429 concussions were reported over
      1,981,284 AE across all levels (Rate: 0.72/1000AE). Overall, most concussions
      were caused by player contact (84.7%). During games, a greater proportion of
      youth football concussions (14.7%) were caused by surface contact than high
      school (7.3%, IPR = 2.02; 95% confidence interval [CI]: 1.10-3.72) and college
      (7.1%, IPR = 2.07, 95% CI: 1.02-4.23) football. Compared with college football
      concussions (90.2%), a smaller proportion of youth (80.0%, IPR = 0.89, 95% CI:
      0.79-0.99) and high school (83.2%, IPR = 0.92, 95% CI: 0.86-0.99) football
      concussions were caused by player contact. A greater proportion of game youth
      football concussions (42.1%) occurred while an individual was being tackled than
      occurred in high school (23.2%, IPR = 1.81, 95% CI: 1.34-2.45) and college
      (23.0%, IPR = 1.83, 95% CI: 1.29-2.62) football. Findings were similar during
      practices. Compared with college football game concussions (15.8%), a smaller
      proportion of youth (6.3%, IPR = 0.40, 95% CI: 0.17-0.93) and high school (9.5%,
      IPR = 0.60, 95% CI: 0.38-0.95) football game concussions occurred while an
      individual was being blocked. Concussion mechanism and activity differences
      should be considered when developing concussion prevention and sport-safety
      methods specific to different age levels, in order to maximize effectiveness.

PMID- 28490229
TI  - Changes in blood pressure among patients in the Ontario Telehomecare programme:
      An observational longitudinal cohort study.
AB  - Background The objective of this study was to investigate the changes in blood
      pressure among patients enrolled in the Telehomecare programme in Ontario,
      Canada. Methods This observational study utilised a prospective longitudinal
      cohort design, including patients with heart failure and chronic obstructive
      pulmonary disease enrolled in the Ontario Telehomecare programme from July 2012
      to July 2015. The outcome of interest was change in mean (biweekly) systolic and
      diastolic blood pressure levels over a six-month period. Patient data were
      extracted from the Ontario Telemedicine Network database, and analysed using
      generalised linear mixed model procedures. Results Overall, we analysed data for
      3513 patients. Patients were on average 74.1 +/- 11.4 years of age; almost half
      were men, 62% had heart failure, 55% chronic obstructive pulmonary disease and
      29% diabetes. At baseline, the mean systolic and diastolic blood pressure levels
      were 130.4 +/- 19.1 mmHg and 72.2 +/- 12.5 mmHg for the total sample. At six
      months, the adjusted reduction in systolic and diastolic blood pressure values
      were 4.0 mmHg (95% confidence interval: -4.5 to -3.5) and 2.7 mmHg (95%
      confidence interval: -3.1 to -2.4), respectively. In a subgroup of 1220 patients
      with uncontrolled blood pressure at baseline (systolic/diastolic blood pressure
      of 150.7 +/- 10.2 mmHg/80.2 +/- 13.5 mmHg) the adjusted reduction in systolic
      blood pressure was 12.5 mmHg (95% confidence interval: -13.4 to -11.6) and in
      diastolic blood pressure was 7.1 mmHg (95% confidence interval: -7.8 to -6.5)
      over the six-month period. Conclusions Blood pressure levels were significantly
      reduced in patients enrolled in the Telehomecare programme, with changes being
      more pronounced in patients with uncontrolled blood pressure. The sustainability
      of decreased blood pressure on other clinical outcomes needs further evaluation.

PMID- 28490230
TI  - Acceptability of In Utero Hematopoietic Cell Transplantation for Sickle Cell
      Disease.
AB  - BACKGROUND: In utero hematopoietic cell transplantation (IUHCT) has curative
      potential for sickle cell disease (SCD) but carries a risk of fetal demise.
      METHODS: We assessed the conditions under which parents of children with SCD and
      young adults with SCD would consider IUHCT in a future pregnancy, given a 5%
      fixed risk of fetal demise. Participants were randomized to consider a
      hypothetical cure rate (20%, 40%, or 70%). Subsequently, cure rate was either
      increased or decreased depending on the previous answer to reveal the lowest
      acceptable rate. Participants also completed the Pediatric Research Participation
      Questionnaire (PRPQ) and an omission scale. RESULTS: Overall, 74 of 79 (94%)
      participants were willing to consider IUHCT, and 52 (66%) participants accepted
      IUHCT at a cure rate of 40%, the estimated rate of therapeutic mixed chimerism.
      Participants with higher scores on the PRPQ perceived benefits scale were more
      likely to participate at lower cure rates (OR 1.08, p=0.007) and participants
      with a greater degree of omission bias were less likely to participate at lower
      cure rates (OR 0.83, p=0.04). Demographics and SCD severity were not
      significantly associated with acceptability of IUHCT. CONCLUSION: This study
      suggests that the majority of parents >and young adults would consider IUHCT
      under expected therapeutic conditions.

PMID- 28490231
TI  - Energy and Protein Delivery in Overweight and Obese Children in the Pediatric
      Intensive Care Unit.
AB  - BACKGROUND: Early and optimal energy and protein delivery have been associated
      with improved clinical outcomes in the pediatric intensive care unit (PICU).
      Overweight and obese children in the PICU may be at risk for suboptimal
      macronutrient delivery; we aimed to describe macronutrient delivery in this
      cohort. METHODS: We performed a retrospective study of PICU patients ages 2-21
      years, with body mass index (BMI) >=85th percentile and >48 hours stay. Nutrition
      variables were extracted regarding nutrition screening and assessment, energy and
      protein prescription, and delivery. RESULTS: Data from 83 patient encounters for
      52 eligible patients (52% male; median age 9.6 [5-15] years) were included. The
      study cohort had a longer median PICU length of stay (8 vs 5 days, P < .0001) and
      increased mortality rate (6/83 vs 182/5572, P = .045) than concurrent PICU
      patient encounters. Detailed nutrition assessment was documented for 60% (50/83)
      of patient encounters. Energy expenditure was estimated primarily by predictive
      equations. Stress factor >1.0 was applied in 44% (22/50). Median energy delivered
      as a percentage of estimated requirements by the Schofield equation was 34.6% on
      day 3. Median protein delivered as a percentage of recommended intake was 22.1%
      on day 3. CONCLUSIONS: The study cohort had suboptimal nutrition assessments and
      macronutrient delivery during their PICU course. Mortality and duration of PICU
      stay were greater when compared with the general PICU population. Nutrition
      assessment, indirect calorimetry-guided energy prescriptions, and optimizing the
      delivery of energy and protein must be emphasized in this cohort. The impact of
      these practices on clinical outcomes must be investigated.

PMID- 28490232
TI  - The Candy-Plug Technique: Technical Aspects and Early Results of a New
      Endovascular Method for False Lumen Occlusion in Chronic Aortic Dissection.
AB  - PURPOSE: To describe the technical aspects and early results of the Candy-Plug
      technique for endovascular false lumen occlusion in chronic aortic dissection.
      METHODS: A retrospective single-center study analyzing 18 consecutive patients
      (mean age 63 years, range 44-76; 16 men) with thoracic false lumen aneurysm in
      chronic aortic dissection. All patients underwent thoracic endovascular aortic
      repair with false lumen occlusion using the Candy-Plug technique. Primary
      endpoints consisted of technical success (successful deployment) and clinical
      success (no false lumen backflow). Secondary endpoints included 30-day mortality
      and morbidity as well as aortic remodeling during follow-up. RESULTS: Technical
      success was 100%. Additional intraprocedural false lumen embolization at the
      Candy-Plug level was needed in 1 patient due to persisting false lumen backflow
      on the final angiogram (clinical success 94%). There were no intraprocedural
      complications. In the perioperative period, there were 3 minor complications:
      transient mild spinal cord ischemia, cervical hematoma after carotid-subclavian
      bypass, and a common femoral artery pseudoaneurysm. No deaths or reinterventions
      occurred. Complete distal false lumen occlusion was present on postoperative
      computed tomography in 15 patients, while 3 had minor contrast enhancement in the
      distal false lumen. Over a mean 9-month follow-up (range 0-26), 1 patient died
      due to rupture. Follow-up >6 months was available in 10 patients (mean 14.7
      months, range 7-26): 7 patients showed aortic remodeling, while aneurysm size was
      stable in 3 patients. CONCLUSION: The Candy-Plug technique is a feasible
      endovascular method to achieve false lumen occlusion and aortic remodeling in
      chronic aortic dissection. It is associated with low morbidity and mortality due
      to its minimal invasiveness.

PMID- 28490233
TI  - Update on Finger-Application-Type Noninvasive Continuous Hemodynamic Monitors
      (CNAP and ccNexfin): Physical Principles, Validation, and Clinical Use.
AB  - The CNAP HD Monitor (CNSystems, Graz, Austria) and the ccNexfin (The ClearSight
      System: Edwards Lifesciences Corporation, Irvine, CA) are continuous, noninvasive
      blood pressure monitors using a finger-application device. These devices show a
      promising ability to allow for rapid detection of hemodynamic derangement when
      compared with oscillometry. The accuracy and precision of these devices as blood
      pressure monitors has been evaluated when compared with intra-arterial catheters.
      Additionally, they can be used to measure beat-to-beat cardiac output (CO). As CO
      monitors, they are capable of trending changes in CO when compared with a
      transpulmonary thermodilution monitor. Difficulty with use in critically ill and
      awake patients has been encountered because of altered microvascular physiology
      and patient movement. The principles of operation and clinical validation of
      these devices are presented. The clinicians who are interested in using these
      devices in their clinical setting should be aware of the relatively large bias
      and CIs in the hemodynamic measurements.

PMID- 28490234
TI  - Are self-rated and behavioural measures of impulsivity in bipolar disorder mainly
      related to comorbid substance use problems?
AB  - INTRODUCTION: Impulsivity is a multidimensional feature observed in bipolar
      disorder (BD) and substance use disorder (SUD). We previously found a
      relationship between SUD and risk taking in BD. It is still unclear whether self
      rated and behavioral impulsivity measures differ between BD with and without
      comorbid SUD, or are specific to BD. METHODS: 93 adults with BD with comorbid
      SUD, 91 BD without SUD, and 93 healthy controls (HC) were administered the
      Barratt Impulsivity Scale (BIS), the Behavioral Inhibition/Behavioral Activation
      System Scale (BIS/BAS), and the Cambridge Neuropsychological Test Automated
      Battery. Analyses compared impulsivity measures across groups controlling for
      age. Discriminant function analyses (DFA) assessed the combination of variables
      effectively predicting group membership. RESULTS: BD displayed increased BIS,
      BIS/BAS scores, reduced performance on the Cambridge Gambling and Rapid Visual
      Processing, and Affective Go/No-Go tasks compared to HC. Comparisons between BD
      with and without SUD showed increased BIS Motor impulsiveness. The overall
      predictive power of DFA was weak. CONCLUSIONS: Some facets of impulsivity are a
      core trait of BD and are partially independent from the presence of SUD. Motor
      impulsiveness may be distinctive of BD+SUD. More research is needed to understand
      the role of impulsive behaviors as risk factors for relapse in SUD.

PMID- 28490235
TI  - Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by
      Inhibiting Mitogen-Activated Protein Kinase Activation.
AB  - Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese
      medicine and a popular dietary supplement worldwide. In in vivo situations,
      polyphenolic anthranoids are extensively broken down into glucuronides and
      sulfate metabolites by the gut and the liver. The anti-inflammatory potential of
      aloe metabolites has not been examined. The aim of this study was to investigate
      the anti-inflammatory effects of aloe metabolites from in vitro
      (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS
      activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The
      production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and
      NO was determined by ELISA and Griess reagents, respectively. The expression
      levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that
      aloe metabolites inhibited the expression of iNOS, decreased the production of
      TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of
      MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites
      reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine
      peritoneal macrophages. Furthermore, aloe administration significantly reduced
      the NO level and exhibited protective effects against sepsis-related death in LPS
      induced septic mice. These results suggest that aloe metabolites exerted anti
      inflammatory effects in vivo, and that these effects were associated with the
      inhibition of inflammatory mediators. Therefore, aloe could be considered an
      effective therapeutic agent for the treatment of sepsis.

PMID- 28490236
TI  - Cinnamyl Alcohol, the Bioactive Component of Chestnut Flower Absolute, Inhibits
      Adipocyte Differentiation in 3T3-L1 Cells by Downregulating Adipogenic
      Transcription Factors.
AB  - The extract of chestnut (Castanea crenata var. dulcis) flower (CCDF) has
      antioxidant and antimelanogenic properties, but its anti-obesity properties have
      not been previously examined. In this study, we tested the effect of CCDF
      absolute on adipocyte differentiation by using 3T3-L1 cells and determining the
      bioactive component of CCDF absolute in 3T3-L1 cell differentiation. CCDF
      absolute (0.1-100[Formula: see text][Formula: see text]g/mL) did not change 3T3
      L1 cell viability. At 50[Formula: see text][Formula: see text]g/mL and
      100[Formula: see text][Formula: see text]g/mL, the absolute significantly reduced
      the accumulation of lipid droplets in 3T3-L1 cells that were induced by culture
      in medium containing 3-isobutyl-1-methylxanthine/dexamethasone/insulin (MDI).
      GC/MS analysis showed that CCDF absolute contains 10 compounds. Among these
      compounds, cinnamyl alcohol (3-phenyl-2-propene-1-ol) dose-dependently inhibited
      the increased accumulation of lipid droplets in MDI-contained medium-cultured 3T3
      L1 cells at a concentration range of 0.1[Formula: see text][Formula: see
      text]g/mL to 10[Formula: see text][Formula: see text]g/mL that did not cause
      cytotoxicity in 3T3-L1 cells. The inhibitory effect was significant at 5[Formula:
      see text][Formula: see text]g/mL ([Formula: see text] of response in MDI alone
      treated state, [Formula: see text]) and 10[Formula: see text][Formula: see
      text]g/mL ([Formula: see text] of response in MDI alone-treated state, [Formula:
      see text]). Moreover, the enhanced expression of obesity-related proteins
      (PPAR[Formula: see text], C/EBP[Formula: see text], SREBP-1c, and FAS) in MDI
      medium-cultivated 3T3-L1 cells was significantly attenuated by the addition of
      cinnamyl alcohol at 5[Formula: see text][Formula: see text]g/mL and 10[Formula:
      see text][Formula: see text]g/mL. These findings demonstrate that cinnamyl
      alcohol suppresses 3T3-L1 cell differentiation by inhibiting anti-adipogenesis
      related proteins, and it may be a main bioactive component of CCDF absolute,
      exerting antidifferentiation action in 3T3-L1 cells. Therefore, cinnamyl alcohol,
      as well as CCDF absolute, may be potential candidates for the prevention or
      treatment of obesity.

PMID- 28490237
TI  - Phytochemistry and Pharmacological Activities of the Genus Swertia
      (Gentianaceae): A Review.
AB  - Swertia plants have been considered to be medicinal plants useful for the
      treatment of various ailments for thousands of years, especially in Asian
      countries. This is due to the broad variety of chemical compounds that provide
      multiple ligands for bonding to different endogenous biomacromolecules for
      patients. Chemical constituents and pharmacological activities of Swertia plants
      are summarized in this paper. Approximately 419 metabolites and 40 bioactive
      compounds have been reported from 30 Swertia species, including xanthones,
      flavonoids, seco-iridiods, iridiods, triterpenoids, alkaloids, volatiles, and
      other secondary metabolites. The bioactivities of Swertia plants include
      anticarcinogenic, hepatoprotective, anti-oxidant, hypoglycemic, anthelmintic,
      antibacterial, antifungal, anti-diabetic, gut, and airways modulatory,
      metabolizing isozymes inhibitory, neuroprotective, HIV-I reverse transcriptases
      inhibitory, anticholinergic, and CNS-depressant activities, etc. In addition,
      biosynthetic pathways of xanthones, and seco-iridiods, two most important
      secondary metabolites for Swertia, are elucidated. The xanthones biosynthetic
      pathway is a mixed biosynthetic pathway involved the shikimate and the malonate
      routes, and the seco-iridoid pathway starts with geraniol derived from IPP which
      is produced either via the MEP or the MVA pathway. This review will offer a
      reference for future researches on the protection of natural resources, the
      investigation of therapeutic basis, new drug development, and so forth. Metabolic
      pathways of some crucial active compounds were also discussed in this review.

PMID- 28490238
TI  - 22 controlled trials in Education for Primary Care 1990-2015.

PMID- 28490239
TI  - Components of Successful Staple Food Fortification Programs: Lessons From Latin
      America.
AB  - BACKGROUND: There are few effectiveness evaluations of food fortification
      programs, and little is known about what makes programs successful. OBJECTIVE: We
      examined 3 food fortification programs in Latin America to identify common
      features that might explain their success and to draw lessons for program design
      and implementation everywhere: The vitamin A fortification of sugar in Guatemala
      with impact on vitamin A status of the population, the fortification of a basket
      of foods with iron and other micronutrients in Costa Rica with impact on iron
      status and anemia in women and children, and the fortification of wheat flour
      with folic acid in Chile, which reduced the incidence of neural tube defects.
      METHODS: We identified pertinent literature about these preselected programs and
      asked regional experts for any additional information. We also conducted
      structured interviews of key informants to provide historical and contextual
      information. RESULTS: Institutional research capacity and champions of
      fortification are features of successful programs in Latin America. We also found
      that private/public partnerships (industry, government, academia, and civil
      society) might be key for sustainability. To achieve impact, program managers
      need to use fortification vehicles that are consumed by the nutritionally
      vulnerable and to add bioavailable fortificants at adequate content levels in
      order to fill dietary gaps and reduce micronutrient deficiencies. Adequate
      monitoring and quality control are essential. CONCLUSIONS: For future programs,
      we recommend that the evaluation be specified up-front, including a baseline/end
      line and data collection along the program impact pathway to inform needed
      improvements and to strengthen causal inferences.

PMID- 28490240
TI  - [Body image and body image distortion].
AB  - The aim of this literature review is to integrate the results of various studies
      regarding body image and body image distortion into a unified framework. The
      concept of body image is complex and can be interpreted from multiple points of
      view. The first part of the study touches upon different age characteristics,
      attentional focus on the body, the early and important role of the body in
      identity formation, specific features in adolescence, gender differences, and the
      often-observed stability of body image (distortion), which may be present as a
      (trait) marker throughout the lifespan. The second part focuses on the
      organization of body image. The results of different studies on cognitive
      information processing are reviewed, the question of perceptual accuracy is
      addressed and the concepts of embodiment are examined. The third topic is body
      image distortion. First, the concept is contextualized along different continua,
      then discussed in a clinical sense along with the complexity of diagnostic
      methods, as well as the state and trait aspects of body image distortion. Orv
      Hetil. 2017; 158(19): 723-730.

PMID- 28490241
TI  - [Dr. Ferenc Baranyi (1936-2016). Former Minister of Health of Romania].

PMID- 28490242
TI  - [Telemetry data based on comparative study of physical activity in patients with
      resynchronization device].
AB  - INTRODUCTION: The effect of regular physical activity on health is widely
      recognized, but several studies have shown its key importance for heart patients.
      AIM: The present study aimed to define the PA % values, and to convert them into
      metabolic equivalent values (MET), which describes oxygen consumption during
      physical activity. METHOD: A total of seventeen patients with heart disease; 3
      females and 14 males; age: 57.35 yrs +/- 9.54; body mass 98.71 +/- 9.89 kg;
      average BMI 36.69 +/- 3.67 were recruited into the study. The measured values
      from Cardiac Resynchronisation Therapy devices and outer accelerometers
      (ActiGraph GT3X+) were studied over a 7-day time period. Using the two sets of
      values describing physical performance, linear regression was calculated
      providing a mathematical equation, thus, the Physical Activity values in
      percentage were converted into MET values. RESULTS: During the 6-minute walk test
      the patients achieved an average of 416.6 +/- 48.2 m. During 6MWT the measured
      values averaged at 1.85 +/- 0.18 MET's, and MET values averaged at 1.12 +/- 0.06
      per week. It clearly shows that this test is a challenge for the patients
      compared to their daily regular physical activity levels. CONCLUSION: With our
      method, based on the values received from the physical activity sensor implanted
      into the resynchronisation devices, changes in patients' health status could be
      monitored telemetrically with the assistance from the implanted electronic
      device. Orv Hetil. 2017; 158(17): 748-753.

PMID- 28490244
TI  - [Investigating the efficacy of nutrition therapy for outpatients with
      inflammatory bowel disease].
AB  - INTRODUCTION: Inflammatory bowel diseases can cause malnutrition (due to
      inflammatory cytokine production, catabolic states after surgery, restricted
      diet), which is difficult to treat by nutritional therapy. AIM: Investigating the
      efficacy of nutrition therapy. METHOD: Combined malnutrition risk screening
      (questionnaires and body composition analysis), at the beginning of the research
      and after a 1 year period. RESULTS: 205 patients were screened, 82 were
      malnourished. A total of 44 received nutritional intervention for 1 year, for 45%
      dietary management was satisfactory, 50% needed oral nutritional supplements and
      5% received home parenteral nutrition. These interventions reduced the number of
      patients considered by both measuring methods in high risk from 31 to 21,
      increased the body weight and fat-free mass in 8 and 9 cases significantly (i.e.,
      with more than 10%), and improved the indices as well (DeltaBMI: +1.3 kg/m2, p =
      0.035 s., DeltaFFMI: +0.5 kg/m2, p = 0.296 n.s.). The main limitations of our
      research are the relatively low number of cases and the mono-centric involvement.
      CONCLUSIONS: We recommend combined malnutrition risk screening for all patients
      with inflammatory bowel disease due to the high risk of malnutrition, and follow
      up of the malnourished patients to monitor the efficacy of their nutrition
      therapy. Orv Hetil. 2017; 158(19): 731-739.

PMID- 28490245
TI  - [Childhood traumatization, dissociation and nonsuicidal self-injurious behavior
      in borderline personality disorder].
AB  - INTRODUCTION: Childhood traumatization plays a significant role in the etiology
      of borderline personality disorder. Studies found a significant association
      between childhood traumatization, dissociation, and nonsuicidal self-injurious
      behavior. AIM: The aim of our study was to assess dissociation and nonsuicidal
      self-injury among borderline inpatients and to reveal the association between
      childhood traumatization, dissociation, and self-injurious behavior. METHOD: The
      sample consisted of 80 borderline inpatients and 73 depressed control patients.
      Childhood traumatization, dissociation and self-injurious behavior were assessed
      by questionnaires. RESULTS: Borderline patients reported severe and multiplex
      childhood traumatization. Cumulative trauma score and sexual abuse were the
      strongest predictors of dissociation. Furthermore, we have found that cumulative
      trauma score and dissociation were highly predictive of self-injurious behavior.
      CONCLUSION: Our results suggest that self-injurious behavior and dissociation in
      borderline patients can be regarded as indicators of childhood traumatization.
      Orv Hetil. 2017; 158(19): 740-747.

PMID- 28490246
TI  - Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary
      tuberculosis in Papua New Guinea.
AB  - BACKGROUND: The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous
      detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This
      study examined the accuracy of Xpert in children with suspected pulmonary
      tuberculosis (PTB). METHODS: Children admitted to Port Moresby General Hospital
      with suspected PTB were prospectively enrolled between September 2014 and March
      2015. They were classified into probable, possible and TB-unlikely groups. Sputum
      or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial
      culture was undertaken on a subset. Children were diagnosed with TB on the basis
      of standard criteria which were used as the primary reference standard. Xpert,
      smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the
      primary reference standard. RESULTS: A total of 93 children <=14 years with
      suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%)
      possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the
      primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall,
      including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three
      (13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB
      than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an
      Edwards TB score of >=7 was 31% (25/80), 16% (13/80) and 90% (72/80),
      respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13),
      respectively, when compared with the primary reference standard. CONCLUSION:
      Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB,
      although a positive result is confirmatory. A detailed history and examination,
      standardised clinical criteria, radiographs and available tests remain the most
      appropriate way of diagnosing TB in children in resource-limited countries. Xpert
      helps confirm PTB better than AFB smear, and identifies rifampicin resistance.
      Practical guidelines should be used to identify children who will benefit from an
      Xpert assay.

PMID- 28490247
TI  - Effects of valent image-based secondary tasks on verbal working memory.
AB  - Two experiments examined if exposure to emotionally valent image-based secondary
      tasks introduced at different points of a free recall working memory (WM) task
      impair memory performance. Images from the International Affective Picture System
      (IAPS) varied in the degree of negative or positive valance (mild, moderate,
      strong) and were positioned at low, moderate and high WM load points with
      participants rating them based upon perceived valence. As predicted, and based on
      previous research and theory, the higher the degree of negative (Experiment 1)
      and positive (Experiment 2) valence and the higher the WM load when a secondary
      task was introduced, the greater the impairment to recall. Secondary task images
      with strong negative valance were more disruptive than negative images with lower
      valence at moderate and high WM load task points involving encoding and/or
      rehearsal of primary task words (Experiment 1). This was not the case for
      secondary tasks involving positive images (Experiment 2), although participant
      valence ratings for positive IAPS images classified as moderate and strong were
      in fact very similar. Implications are discussed in relation to research and
      theory on task interruption and attentional narrowing and literature concerning
      the effects of emotive stimuli on cognition.

PMID- 28490249
TI  - Novel single marker approach to estimation of lower extremity movement.
AB  - Sacrum motion is used extensively in studying the biomechanical characteristics
      of walking. This study aimed at investigating the potential of sacrum motion to
      provide an estimation of important gait events in conjunction with predicting the
      motion of lower extremity segments. Three-dimensional trajectories of 37
      reflective markers placed on anatomical landmarks of 14 healthy subjects were
      recorded while walking at self-selected normal walking speed on treadmill.
      Elevation angles of lower extremity segments in sagittal plane were estimated
      using the lower extremity markers. Regression analysis was used to estimate the
      ability of sacrum kinematic variables to predict lower extremity elevation
      angles. Prediction was performed at 10 different gait events extracted from three
      dimensional sacrum trajectories. The coefficients of the predicting variables
      were analyzed at these events. The results indicated that heel strike and toe off
      event instances identified using trajectory of sacrum marker were close to the
      results of accurate kinematic methods. Additionally, the motion of this point was
      able to predict lower extremity angles with a suitable coefficient of
      determination at early single support and mid-swing events. A range of
      musculoskeletal disorders could be identified using the elevation angles at these
      events. This study could be considered as a step toward development of effective
      and simplified instrumentation in clinical diagnosis of gait disorders.

PMID- 28490248
TI  - Sodium louroyl sarcosinate (sarkosyl) modulate amyloid fibril formation in hen
      egg white lysozyme (HEWL) at alkaline pH: a molecular insight study.
AB  - Amyloid fibril formation is responsible for several neurodegenerative diseases
      and are formed when native proteins misfold and stick together with different
      interactive forces. In the present study, we have determined the mode of
      interaction of the anionic surfactant sarkosyl with hen egg white lysozyme (HEWL)
      [EC No. 3.2.1.17] at two pHs (9.0 and 13.0) and investigated its impact on
      fibrillogenesis. Our data suggested that sarkosyl is promoting amyloid fibril
      formation in HEWL at the concentration range between 0.9 and 3.0 mM and no
      amyloid fibril formation was observed in the concentration range of 3.0-20.0 mM
      at pH 9.0. The results were confirmed by several biophysical and computational
      techniques, such as turbidity measurement, dynamic light scattering, Raleigh
      scattering, ThT fluorescence, intrinsic fluorescence, far-UV CD and atomic force
      microscopy. Sarkosyl was unable to induce aggregation in HEWL at pH 13.0 as
      confirmed by turbidity and RLS measurements. HEWL forms larger amyloid fibrils in
      the presence of 1.6 mM of sarkosyl. The spectroscopic, microscopic and molecular
      docking data suggest that the negatively charged carboxylate group and 12-carbon
      hydrophobic tail of sarkosyl stimulate amyloid fibril formation in HEWL via
      electrostatic and hydrophobic interaction. This study leads to new insight into
      the process of suppression of fibrillogenesis in HEWL which can be prevented by
      designing ligands that can retard the electrostatic and hydrophobic interaction
      between sarkosyl and HEWL.

PMID- 28490250
TI  - Effects of acrylamide graded doses on metallothioneins I and II induction and DNA
      fragmentation: Bochemical and histomorphological changes in the liver of adult
      rats.
AB  - The present study investigates the toxic effects of acrylamide (ACR) administered
      to rats at two doses on (i) oxidative stress and disruption of pro
      oxidant/antioxidant balance in hepatic cells and (ii) its correlation with
      metallothioneins (MTs) genes expression, DNA damage and histomorphological
      changes. Treated rats with 20 and 40 mg/kg body weight of ACR led to an increase
      in malondialdehyde, hydrogen peroxide, advanced oxidation protein products,
      protein carbonyl levels as well as an alteration in the antioxidant status. Total
      MT content in the liver and MT I and MT II genes induction were increased. Plasma
      transaminases activities, albumin, total protein and glucose levels were also
      increased, while alkaline phosphatase activity was decreased. Moreover, total
      cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C)
      levels, TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios
      were increased, while HDL-C decreased in a dose-dependent manner. A random DNA
      degradation was observed only in the liver of ACR-treated rats with the highest
      dose. These changes were confirmed by histopathological observations.

PMID- 28490251
TI  - Ampicillin-incorporated alginate-chitosan fibers from microfluidic spinning and
      for vitro release.
AB  - The fibrous drug-loading capability, degradation profile, drug release behavior
      and mechanical performance were found to be controlled by regulating the amount
      of IPA and chitosan, which delayed the degradable time-scale and improved the
      drug loading capacity. Six types of alginate fibers were spun by combining two
      distinct core flows with deionized water-based, ethanol-based and isopropyl
      alcohol-based sheath fluid, respectively. The as prepared fibers were analyzed
      and compared by the characterization of SEM, mass loss, ICP, FTIR, XRD, UV,
      mechanics performance testing and antibacterial activity tests. The results
      showed that fibers in the isopropyl alcohol with low polarity sheath flow
      exhibited higher-ordered structure. Also, incorporation of chitosan for the core
      stream strengthened the degree of crosslinking among the molecular chain, and
      thus made the fiber entrapped more drug of ampicillin molecular. The fibers,
      possessing superior mechanical properties, preferable drug loading capability,
      more prolonged drug release behavior and outstanding antibiotic activity, may
      offer a promising candidate for biomaterials, such as fibrous drug carrier and
      antibacterial sutures.

PMID- 28490252
TI  - Visceral leishmaniosis in immunocompromised host: an update and literature
      review.
AB  - Visceral leishmaniasis (VL) is a chronic infectious disease endemic in tropical
      and sub-tropical areas including the Mediterranean basin, caused by a group of
      protozoan parasites of the genus Leishmania and transmitted by phlebotomine
      sandflies. Immunocompromised patients, in particular HIV positive, are considered
      at risk of VL. They report atypical signs and poor response to treatment due to
      impairment of T-helper and regulatory cells activity. Laboratory diagnosis is
      based on microscopy on bone marrow or spleen aspirates. Value of serology remains
      high in term of sensibility, but a positive test must be confirmed by microscopy
      or molecular tests. Treatment is based on Liposomal amphotericin B whose
      administration is associated to lower incidence of side effects, in respect to
      antimonials and other formulations of AmB. Use of Miltefosine needs further
      investigation when L. infantum is the causative agent. Frequent relapses are
      observed in co-infected HIV who can benefit of a second cycle.

PMID- 28490253
TI  - Science to the rescue or contingent progress? Comparing 10 years of public,
      expert and policy discourses on new and emerging science and technology in the
      United Kingdom.
AB  - Over the past 10 years, numerous public debates on new and emerging science and
      technologies have taken place in the United Kingdom. In this article, we
      characterise the discourses emerging from these debates and compare them to the
      discourses in analogous expert scientific and policy reports. We find that while
      the public is broadly supportive of new scientific developments, they see the
      risks and social and ethical issues associated with them as unpredictable but
      inherent parts of the developments. In contrast, the scientific experts and
      policymakers see risks and social and ethical issues as manageable and
      quantifiable with more research and knowledge. We argue that these differences
      amount to two different sociotechnical imaginaries or views of science and how it
      shapes our world - an elite imaginary of 'science to the rescue' shared by
      scientists and policymakers and public counter-imaginary of 'contingent
      progress'. We argue that these two imaginaries indicate that, but also help
      explain why, public dialogue has had limited impact on public policy.

PMID- 28490254
TI  - Validating Dose Uncertainty Estimates Produced by AUTODIRECT: An Automated
      Program to Evaluate Deformable Image Registration Accuracy.
AB  - Deformable image registration is a powerful tool for mapping information, such as
      radiation therapy dose calculations, from one computed tomography image to
      another. However, deformable image registration is susceptible to mapping errors.
      Recently, an automated deformable image registration evaluation of confidence
      tool was proposed to predict voxel-specific deformable image registration dose
      mapping errors on a patient-by-patient basis. The purpose of this work is to
      conduct an extensive analysis of automated deformable image registration
      evaluation of confidence tool to show its effectiveness in estimating dose
      mapping errors. The proposed format of automated deformable image registration
      evaluation of confidence tool utilizes 4 simulated patient deformations (3 B
      spline-based deformations and 1 rigid transformation) to predict the uncertainty
      in a deformable image registration algorithm's performance. This workflow is
      validated for 2 DIR algorithms (B-spline multipass from Velocity and Plastimatch)
      with 1 physical and 11 virtual phantoms, which have known ground-truth
      deformations, and with 3 pairs of real patient lung images, which have several
      hundred identified landmarks. The true dose mapping error distributions closely
      followed the Student t distributions predicted by automated deformable image
      registration evaluation of confidence tool for the validation tests: on average,
      the automated deformable image registration evaluation of confidence tool
      produced confidence levels of 50%, 68%, and 95% contained 48.8%, 66.3%, and 93.8%
      and 50.1%, 67.6%, and 93.8% of the actual errors from Velocity and Plastimatch,
      respectively. Despite the sparsity of landmark points, the observed error
      distribution from the 3 lung patient data sets also followed the expected error
      distribution. The dose error distributions from automated deformable image
      registration evaluation of confidence tool also demonstrate good resemblance to
      the true dose error distributions. Automated deformable image registration
      evaluation of confidence tool was also found to produce accurate confidence
      intervals for the dose-volume histograms of the deformed dose.

PMID- 28490255
TI  - Developing a taxonomy of coordination behaviours in nuclear power plant control
      rooms during emergencies.
AB  - This study aims to develop a taxonomy of coordination behaviours during
      emergencies in nuclear power plants (NPPs). We summarised basic coordination
      behaviours from literature in aviation, health care and nuclear field and
      identified coordination behaviours specific to the nuclear domain by interviewing
      and surveying control crew operators. The established taxonomy includes 7
      workflow stages and 24 basic coordination behaviours. To evaluate the reliability
      and feasibility of the taxonomy, we analysed 12 videos of operators' training
      sessions by coding coordination behaviours with the taxonomy and the inter-rater
      reliability was acceptable. Further analysis of the frequency, the duration and
      the direction of the coordination behaviours revealed four coordination problems.
      This taxonomy provides a foundation of systematic observation of coordination
      behaviours among NPP crews, advances researchers' understanding of the
      coordination mechanism during emergencies in NPPs and facilitate the possibility
      to deepen the understanding of the relationships between coordination behaviours
      and team performance. Practitioner Summary: A taxonomy of coordination behaviours
      during emergencies in nuclear power plants was developed. Reliability and
      feasibility of the taxonomy was verified through the analysis of 12 training
      sessions. The taxonomy can serve as an observation system for analysis of
      coordination behaviours and help to identify coordination problems of control
      crews.

PMID- 28490257
TI  - Tissue distribution and elimination of deoxynivalenol and ochratoxin A in dietary
      exposed Atlantic salmon (Salmo salar).
AB  - Post-smolt Atlantic salmon (Salmo salar) were fed standard feed with added 2 or 6
      mg kg-1 pure deoxynivalenol (DON), 0.8 or 2.4 mg kg-1 pure ochratoxin A (OTA), or
      no added toxins for up to 8 weeks. The experiments were performed in duplicate
      tanks with 25 fish each per diet group, and the feed was given for three 2-h
      periods per day. After 3, 6 and 8 weeks, 10 fish from each diet group were
      sampled. In the following hours after the last feeding at 8 weeks, toxin
      elimination was studied by sampling three fish per diet group at five time
      points. Analysis of DON and OTA in fish tissues and plasma was conducted by
      liquid chromatography-mass spectrometry and high-pressure liquid chromatography
      with fluorescence detection, respectively. DON was distributed to the liver,
      kidney, plasma, muscle, skin and brain, and the concentrations in liver and
      muscle increased significantly from 3 to 8 weeks of exposure to the high-DON
      diet. After the last feeding at 8 weeks, DON concentration in liver reached a
      maximum at 1 h and decreased thereafter with a half-life (t1/2) of 6.2 h. DON
      concentration in muscle reached a maximum at 6 h and was then eliminated with a
      t1/2 = 16.5 h. OTA was mainly found in liver and kidney, and the concentration in
      liver decreased significantly from 3 to 8 weeks in the high-OTA group. OTA was
      eliminated faster than DON from various tissues. By using Norwegian food
      consumption data and kinetic findings in this study, we predicted the human
      exposure to DON and OTA from fish products through carryover from the feed.
      Following a comparison with tolerable daily intakes, we found the risk to human
      health from the consumption of salmon-fed diets containing maximum recommended
      levels of these toxins to be negligible.

PMID- 28490258
TI  - Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration.
AB  - Mesenchymal stem cells (MSCs) are considered to hold great therapeutic value for
      cell-based therapy and for tissue regeneration in particular. Recent evidence
      indicates that the main underlying mechanism for MSCs' beneficial effects in
      tissue regeneration is based on their capability to produce a large variety of
      bioactive trophic factors that stimulate neighboring parenchymal cells to start
      repairing damaged tissues. These new findings could potentially replace the
      classical paradigm of MSC differentiation and cell replacement. These bioactive
      factors have diverse actions like modulating the local immune system, enhancing
      angiogenesis, preventing cell apoptosis, and stimulating survival, proliferation,
      and differentiation of resident tissue specific cells. Therefore, MSCs are
      referred to as conductors of tissue repair and regeneration by secreting trophic
      mediators. In this review article, we have summarized the studies that focused on
      the trophic effects of MSC within the context of tissue regeneration. We will
      also highlight the various underlying mechanisms used by MSCs to act as trophic
      mediators. Besides the secretion of growth factors, we discuss two additional
      mechanisms that are likely to mediate MSC's beneficial effects in tissue
      regeneration, namely the production of extracellular vesicles and the formation
      of membrane nanotubes, which can both connect different cells and transfer a
      variety of trophic factors varying from proteins to mRNAs and miRNAs.
      Furthermore, we postulate that apoptosis of the MSCs is an integral part of the
      trophic effect during tissue repair.

PMID- 28490256
TI  - How Plastic Are Pericytes?
AB  - Pericytes are defined by both their anatomical location and molecular markers.
      Numerous publications have reported their role as stem cells, contributing to the
      formation of tissues other than blood vessels. However, using cell-lineage
      tracing in a new transgenic mouse model, a recent study shows that in the context
      of aging and some pathologies, Tbx18+ pericytes do not function as stem cells in
      vivo. This study challenges the current view that pericytes can differentiate
      into other cells and reopen questions about their plasticity. This emerging
      knowledge is important not only for our understanding of development but may also
      inform treatments for diseases.

PMID- 28490259
TI  - Recent amendments to NICE's value-based assessment of health technologies:
      implicitly inequitable?

PMID- 28490260
TI  - Emerging treatments for Alzheimer's disease for non-amyloid and non-tau targets.
AB  - INTRODUCTION: The number of people with dementia, including Alzheimer's disease,
      is growing as a result of an ageing global population. Treatments available for
      AD only alleviate the symptoms of the disease, and are effective in some people
      with AD for a limited time. There is no disease-modifying treatment available,
      and despite research efforts, the underlying mechanisms of AD and optimal
      treatment targets have not been fully elucidated. Amyloid and tau are key
      pathological markers of AD with ongoing trials targeting both. However, there are
      also many trials at various stages of development that primarily target other
      markers and processes implicated in the disease, which are now being
      investigated. Areas covered: This review summarizes current treatment approaches
      for AD and explores both repositioned and novel therapies that target non amyloid
      and non tau mechanisms that are in the clinical trials pipeline. This includes
      treatments for cognitive and neuropsychiatric symptoms and potentially disease
      modifying therapies. The studies included in this review have been obtained from
      searches of PubMed and clinical trials databases. Expert commentary: There is a
      renewed energy in identifying better treatments for behavioural symptoms of AD
      using both novel drugs and repositioning existing drugs. Lack of success in
      clinical trials of drugs targeting amyloid and tau have led to a surge in
      targeting alternative mechanisms. Progress in the development of biomarkers will
      provide further tools for clinical trials of potential therapeutics for both
      symptomatic treatment and disease modification in AD.

PMID- 28490261
TI  - Prognostic factors associated with 30-day in-hospital mortality in coagulase
      negative Staphylococcus bacteraemia: no impact of vancomycin minimum inhibitory
      concentration.
AB  - BACKGROUND: The impact of a minimum inhibitory concentration (MIC) of vancomycin
      >=2 mg/L on mortality and the potential benefit of new antistaphylococcal
      treatments in coagulase-negative Staphylococcus (CoNS) bacteraemia remain
      unknown. We assessed the impact of vancomycin MIC on 30-day in-hospital mortality
      and identified factors independently associated with 30-day in-hospital
      mortality. METHODS: All patients presenting significant CoNS bacteraemia in the
      university hospital of Reims, between 01 January 2008 and 31 December 2012, were
      included. Data were retrospectively extracted from the patient records.
      Vancomycin MIC was assessed using the E-test method, and antimicrobial
      susceptibility testing was performed in accordance with the recommendations of
      the Antibiogram Committee of the French Microbiology Society. Cox's Proportional
      Hazards model was used for multivariate analysis. RESULTS: Two hundred and sixty
      nine patients (mean age 61.2 +/- 15.7 years) were included. Foreign material was
      present in 92% of patients and 78.4% of isolated methicillin-resistant strains
      had vancomycin MIC >=2 mg/l. Thirty-day in-hospital mortality was 16%. There was
      no association between vancomycin MIC >=2 mg/l and 30-day in-hospital mortality
      (adjusted Hazard Ratio (aHR) = .80, 95% confidence interval (95%CI) [.30-2.19], p
      = .67). Factors independently associated with 30-day in-hospital mortality were
      age >=75 vs. <=60 years (aHR =3.72, 95%CI [1.39-9.97], p = .009), absence of
      active antibiotic treatment (aHR =5.52, 95%CI [1.13-26.87], p = .03) and acute
      renal failure (aHR =4.45, 95%CI [2.08-9.56], p < .0001). Removal of an infected
      device had a protective effect against 30-day in-hospital mortality (aHR = .23,
      95%CI [.11-.48], p < .0001). CONCLUSIONS: These results suggest that CoNS
      bacteraemia should be managed by removal of the infected device and antibiotic
      treatment such as vancomycin.

PMID- 28490263
TI  - Results of primary end-to-side digital nerve neurorrhaphy in eight patients.

PMID- 28490262
TI  - Methods for safety signal detection in healthcare databases: a literature review.
AB  - INTRODUCTION: With increasing availability, the use of healthcare databases as
      complementary data source for drug safety signal detection has been explored to
      circumvent the limitations inherent in spontaneous reporting. Areas covered: To
      review the methods proposed for safety signal detection in healthcare databases
      and their performance. Expert opinion: Fifteen different data mining methods were
      identified. They are based on disproportionality analysis, traditional
      pharmacoepidemiological designs (e.g. self-controlled designs), sequence symmetry
      analysis (SSA), sequential statistical testing, temporal association rules,
      supervised machine learning (SML), and the tree-based scan statistic. When
      considering the performance of these methods, the self-controlled designs, the
      SSA, and the SML seemed the most interesting approaches. In the perspective of
      routine signal detection from healthcare databases, pragmatic aspects such as the
      need for stakeholders to understand the method in order to be confident in the
      results must be considered. From this point of view, the SSA could appear as the
      most suitable method for signal detection in healthcare databases owing to its
      simple principle and its ability to provide a risk estimate. However, further
      developments, such as automated prioritization, are needed to help stakeholders
      handle the multiplicity of signals.

PMID- 28490264
TI  - Effects of metabolic syndrome on the functional outcomes of corticosteroid
      injection for De Quervain tenosynovitis.
AB  - : Metabolic syndrome is a constellation of medical conditions that arise from
      insulin resistance and abnormal adipose deposition and function. In patients with
      metabolic syndrome and De Quervain tenosynovitis this might affect the outcome of
      treatment by local corticosteroid injection. A total of 64 consecutive patients
      with De Quervain tenosynovitis and metabolic syndrome treated with corticosteroid
      injection were age- and sex-matched with 64 control patients without metabolic
      syndrome. The response to treatment, including visual analogue scale score for
      pain, objective findings consistent with De Quervain tenosynovitis (tenderness at
      first dorsal compartment, Finkelstein test result), and Disability of the Arm,
      Shoulder, and Hand score were assessed at 6, 12, and 24 weeks follow-up.
      Treatment failure was defined as persistence of symptoms or surgical
      intervention. Prior to treatment, patients with metabolic syndrome had mean
      initial pain visual analogue scale and Disability of the Arm, Shoulder, and Hand
      scores similar to those in the control group. The proportion of treatment failure
      in the metabolic syndrome group (43%) was significantly higher than that in the
      control group (20%) at 6 months follow-up. The pain visual analogue scale scores
      in the metabolic syndrome group were higher than the scores in the control group
      at the 12- and 24-week follow-ups. The Disability of the Arm, Shoulder, and Hand
      scores of the metabolic syndrome group were higher (more severe symptoms) than
      those of the control group at the 12- and 24-week follow-ups. Although
      considerable improvements in symptom severity and hand function will likely occur
      in patients with metabolic syndrome, corticosteroid injection for De Quervain
      tenosynovitis is not as effective in these patients compared with age- and sex
      matched controls in terms of functional outcomes and treatment failure. LEVEL OF
      EVIDENCE: III.

PMID- 28490265
TI  - Crush asphyxia and ride-on lawn mowers.
AB  - Search of files at Forensic Science SA, Australia, over the past 20 years (1997
      2016) revealed three cases of death due to crush asphyxia associated with the use
      of ride-on lawn mowers. (1) A 61-year-old man was trapped under a ride-on mower
      that had rolled over. Autopsy examination revealed congestion and petechial
      haemorrhages of the face and chest, and markings on the chest associated with
      underlying rib fractures. (2) A 78-year-old man was trapped under a ride-on mower
      that had also rolled over. Autopsy examination revealed petechial haemorrhages of
      the face and chest and markings on the chest. (3) A 72-year-old man was found
      wedged between a ride-on mower and a tree, with petechial haemorrhages of the
      face and chest, and markings on the front and back of the chest. These cases
      demonstrate a rare cause of crush asphyxia, often in older males in the domestic
      environment, which may arise from more than one mechanism.

PMID- 28490266
TI  - Radiotherapy in Dupuytren's disease: a systematic review of the evidence.
AB  - : Radiotherapy has been advocated as an alternative treatment in early
      Dupuytren's disease. We have systematically reviewed the evidence on the use of
      radiotherapy in Dupuytren's disease. Only six articles met a minimum set
      standard, five of which were retrospective cohort studies and one a randomized
      controlled study. A total of 770 Dupuytren's hands, nearly all with Tubiana stage
      0-1 disease, were irradiated with an average 30 Gy. Disease regression ranged
      from 0%-56%, stability from 14%-98% and progression from 2%-86%. Salvage surgery
      was successful in all cases of disease progression post-radiotherapy. There were
      no reports of adverse wound healing problems associated with such surgery or
      radiotherapy-associated malignancy. On balance, radiotherapy should be considered
      an unproven treatment for early Dupuytren's disease due to a scarce evidence base
      and unknown long-term adverse effects. Well-designed randomized controlled
      studies are required to confirm the benefits of radiotherapy treatment. LEVEL OF
      EVIDENCE: II.

PMID- 28490267
TI  - Darolutamide (ODM-201) for the treatment of prostate cancer.
AB  - INTRODUCTION: Androgen deprivation therapy (ADT) is a mainstay initial treatment
      for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to
      castration-resistant prostate cancer (CRPC) invariably occurs when patients do
      not succumb to another disease or comorbidity. Recognition that the androgen
      receptor (AR) axis continues to drive disease progression has led to the
      development of several AR-directed approved agents, including abiraterone acetate
      and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788),
      has completed early-phase clinical trials, and two global phase III trials are
      currently accruing patients. Areas covered: The unmet clinical need,
      pharmacokinetics, preclinical development, and clinical efficacy and safety of
      darolutamide for the treatment of advanced prostate cancer are reviewed. The
      design of two ongoing phase III trials (ARAMIS and ARASENS) of darolutamide in
      men with non-metastatic CRPC and metastatic HSPC, respectively, are also
      discussed. Expert opinion: Darolutamide is an oral, investigational, high
      affinity AR antagonist which has activity against known AR mutants that confer
      resistance to other second-generation antiandrogens, has minimal blood-brain
      barrier penetration, and does not significantly increase serum testosterone.
      These features may offer potential advantages over the second-generation
      antiandrogens. In the phase I/II ARADES trial, darolutamide demonstrated
      promising antitumor activity and a favorable safety profile in men with
      metastatic CRPC.

PMID- 28490268
TI  - More than meets the MRI: case report of a carcinoid tumour metastasis mimicking a
      meningioma.
AB  - Cerebral metastases from carcinoid tumours are rarely reported and confer a much
      poorer prognosis than carcinoid metastases elsewhere in the body. We describe a
      case of carcinoid brain metastasis closely resembling a meningioma on magnetic
      resonance imaging (MRI), and review current treatment options.

PMID- 28490269
TI  - Investigations of FAK inhibitors: a combination of 3D-QSAR, docking, and
      molecular dynamics simulations studies.
AB  - Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates
      integrin and growth factor signaling pathways, which is a promising therapeutic
      target because of involving in cancer cell migration, proliferation, and
      survival. To investigate the mechanism between FAK and triazinic inhibitors and
      design high activity inhibitors, a molecular modeling integrated with 3D-QSAR,
      molecular docking, molecular dynamics simulations, and binding free energy
      calculations was performed. The optimum CoMFA and CoMSIA models showed good
      reliability and satisfactory predictability (with Q2 = 0.663, R2 = 0.987,
      [Formula: see text] = 0.921 and Q2 = 0.670, R2 = 0.981, [Formula: see text] =
      0.953). Its contour maps could provide structural features to improve inhibitory
      activity. Furthermore, a good consistency between contour maps, docking, and
      molecular dynamics simulations strongly demonstrates that the molecular modeling
      is reliable. Based on it, we designed several new compounds and their inhibitory
      activities were validated by the molecular models. We expect our studies could
      bring new ideas to promote the development of novel inhibitors with higher
      inhibitory activity for FAK.

PMID- 28490270
TI  - Change-point detection for infinite horizon dynamic treatment regimes.
AB  - A dynamic treatment regime is a set of decision rules for how to treat a patient
      at multiple time points. At each time point, a treatment decision is made
      depending on the patient's medical history up to that point. We consider the
      infinite-horizon setting in which the number of decision points is very large.
      Specifically, we consider long trajectories of patients' measurements recorded
      over time. At each time point, the decision whether to intervene or not is
      conditional on whether or not there was a change in the patient's trajectory. We
      present change-point detection tools and show how to use them in defining dynamic
      treatment regimes. The performance of these regimes is assessed using an
      extensive simulation study. We demonstrate the utility of the proposed change
      point detection approach using two case studies: detection of sepsis in preterm
      infants in the intensive care unit and detection of a change in glucose levels of
      a diabetic patient.

PMID- 28490273
TI  - Corrigendum.

PMID- 28490272
TI  - Transfer of the musculocutaneous nerve branch to the brachialis muscle to the
      triceps for elbow extension: anatomical study and report of five cases.
AB  - : We report the study of the anatomical feasibility of transferring the nerve to
      the brachialis muscle to the upper medial head motor branch that innervate the
      triceps, and outcomes of such transfers in restoring elbow extension in five
      patients with posterior cord lesion of the brachial plexus. The length of the
      branches to the brachialis muscle measured 7.6 cm and the triceps upper medial
      head motor branch was 5 cm in 10 adult cadavers. Five male patients were treated
      with this transfer 5 months after the injury (range 4 to 6 months) after
      posterior cord injury of the brachial plexus with a mean follow-up of 31 months
      (range 28 to 36 months). Elbow extension scored M4 in all cases. No complications
      occurred. These preliminary results suggest that transferring the nerve to the
      brachialis muscle is an effective technique for the reconstruction of elbow
      extension after posterior cord brachial plexus injuries. LEVEL OF EVIDENCE: IV.

PMID- 28490271
TI  - Validation of a Cardiovascular Disease Policy Microsimulation Model Using Both
      Survival and Receiver Operating Characteristic Curves.
AB  - BACKGROUND: Despite some advances, cardiovascular disease (CVD) remains the
      leading cause of death and healthcare costs in the United States. We therefore
      developed a comprehensive CVD policy simulation model that identifies cost
      effective approaches for reducing CVD burden. This paper aims to: 1) describe our
      model in detail; and 2) perform model validation analyses. METHODS: The model
      simulates 1,000,000 adults (ages 35 to 80 years) using a variety of CVD-related
      epidemiological data, including previously calibrated Framingham-based risk
      scores for coronary heart disease and stroke. We validated our microsimulation
      model using recent National Health and Nutrition Examination Survey (NHANES)
      data, with baseline values collected in 1999-2000 and cause-specific mortality
      follow-up through 2011. Model-based (simulated) results were compared to observed
      all-cause and CVD-specific mortality data (from NHANES) for the same starting
      population using survival curves and, in a method not typically used for disease
      model validation, receiver operating characteristic (ROC) curves. RESULTS:
      Observed 10-year all-cause mortality in NHANES v. the simulation model was 11.2%
      (95% CI, 10.3% to 12.2%) v. 10.9%; corresponding results for CVD mortality were
      2.2% (1.8% to 2.7%) v. 2.6%. Areas under the ROC curves for model-predicted 10
      year all-cause and CVD mortality risks were 0.83 (0.81 to 0.85) and 0.84 (0.81 to
      0.88), respectively; corresponding results for 5-year risks were 0.80 (0.77 to
      0.83) and 0.81 (0.75 to 0.87), respectively. LIMITATIONS: The model is limited by
      the uncertainties in the data used to estimate its input parameters.
      Additionally, our validation analyses did not include non-fatal CVD outcomes due
      to NHANES data limitations. CONCLUSIONS: The simulation model performed well in
      matching to observed nationally representative longitudinal mortality data. ROC
      curve analysis, which has been traditionally used for risk prediction models, can
      also be used to assess discrimination for disease simulation models.

PMID- 28490274
TI  - Masked primes evoke partial responses.
AB  - Backward-masked primes presented outside conscious awareness can affect responses
      to subsequently presented target stimuli. Differences in response times have been
      used to infer a pattern of sub-threshold activation and subsequent inhibition of
      motor plans associated with the primes. However, it is unclear whether
      competition between alternative responses is fully resolved in the brain or
      whether activated responses can begin being executed before the final decision to
      act has been made. Here, we investigate the dynamics of responses evoked by
      masked primes using a continuous measure - voltage change in force-sensing
      resistors simultaneously in both hands. Masked primes produced the predicted
      pattern of motor activation and subsequent inhibition of the primed response.
      There is no evidence that the effects of masked primes interact with spatial
      compatibility (e.g., Simon) effects, suggesting separate mechanisms underpinning
      these effects. Moreover, masked primes evoked partial motor decisions -
      measurable at the effectors as small amounts of erroneous response - which were
      usually rapidly corrected. Together, these errors and fast corrections question
      the 'sub-threshold' nature of responses evoked by masked primes and provide
      important constraints on models of decision-making.

PMID- 28490275
TI  - Genome-wide sequential, evolutionary, organizational and expression analyses of
      phenylpropanoid biosynthesis associated MYB domain transcription factors in
      Arabidopsis.
AB  - The MYB gene family represents one of the largest groups of transcription factors
      in plants. Recent evidences have also demonstrated key role of MYB transcription
      factors in regulating the expression of major genes involved in the biosynthesis
      of phenylpropanoid compounds which confer biotic and abiotic stress tolerance in
      plant species. However, no comprehensive genome-wide analysis of the
      phenylpropanoid pathway-associated MYB transcription factors has been reported
      thus far. In this study, 11 Arabidopsis MYB proteins, such as MYB3, MYB4, MYB7,
      MYB11, MYB12, MYB32, MYB75, MYB90, MYB111, MYB113, and MYB114 were initially
      identified considering their reported regulatory function in phenylpropanoid
      biosynthesis pathway. Subsequent genome-wide analysis have identified the
      corresponding homologues from Glycine max, Vigna radiata, Oryza sativa, and Zea
      mays, while homologous of Arabidopsis MYB75, MYB90, MYB113, and MYB114 were not
      detected in rice and maize genomes. The identified MYB proteins were classified
      into three groups (I-III) based on phylogeny. Sequence and domain analysis
      revealed presence of two conserved DNA binding MYB domains in the selected MYB
      proteins. Promoter analysis indicated presence of cis-regulatory elements related
      to light signaling, development, and stress response. Expression analysis of
      selected Arabidopsis MYB genes revealed their function in plant development and
      abiotic stress response, consistent with gene ontology annotations. Together,
      these results provide a useful framework for further experimental studies for the
      functional characterization of the target MYB genes in the context of regulation
      of phenylpropanoid biosynthesis and plant stress response.

PMID- 28490276
TI  - Endometrial Stromal and Epithelial Cells Exhibit Unique Aberrant Molecular
      Defects in Patients With Endometriosis.
AB  - CONTEXT: Endometriosis is a chronic inflammatory disease that causes pain and
      infertility in women of reproductive age. OBJECTIVE: To investigate the
      pathologic pathways in endometrial stromal and epithelial cells that contribute
      to the manifestation of endometriosis. DESIGN: In vitro cellular and molecular
      analyses of isolated eutopic endometrial stromal and epithelial cells. METHODS:
      Eutopic stromal and epithelial cells from endometriotic and normal patients were
      isolated by fluorescence-activated cell sorting for paired sibling RNA sequencing
      and microRNA microarray. Aberrant pathways were identified using ingenuity
      pathway analysis networks and confirmed with in vitro modulation of the affected
      pathways in stromal and epithelial cell cultures. RESULTS: Both stromal versus
      epithelial cell types and paired endometriotic versus normal samples exhibited
      distinct hierarchical clustering. Compared to normal samples, there were 151 and
      215 differentially expressed genes in the endometriotic stromal and epithelial
      populations, respectively, and concomitantly 9 and 16 differentially expressed
      microRNAs. Overall, endometriotic stromal and epithelial cells revealed distinct
      defects. In endometriotic stromal cells, key decidualization genes Zinc finger E
      box Binding protein 1 (ZEB1), Heart And Neural crest Derivatives expressed 2
      (HAND2), WNT4, and Interleukin 15 (IL-15) were found to be downregulated and
      Periostin (POSTN) and Matrix Metallopeptidase 7 (MMP7) were upregulated.
      Specifically, ZEB1 was downregulated in stromal cells by aberrant elevation in
      miR-200b. In contrast, ZEB1 was found to be upregulated in endometriotic
      epithelial cells through associated upregulation of transforming growth factor
      beta1 (TGFbeta1), inducer of the TGFbeta1-Bone Morphogenetic Protein 2 (BMP2)
      MMP2-Prostaglandin-endoperoxide Synthase 2 (COX2)-ZEB1 pathway, which activates
      epithelial-mesenchymal transition. CONCLUSION: Manifestation of endometriosis
      involves dysregulation of unique molecular pathways within the diseased
      endometrial stromal and epithelial cells in the endometrium. Targeting the cell
      type-specific defects may offer a novel approach to treating endometriosis.

PMID- 28490277
TI  - Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to
      Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a devastating condition, often leading to life
      long consequences for patients. Even though modern neurointensive care has
      improved functional and cognitive outcomes, efficient pharmacological therapies
      are still lacking. Targeting peripherally derived, or resident inflammatory,
      cells that are rapid responders to brain injury is promising, but complex, given
      that the contribution of inflammation to exacerbation versus improved recovery
      varies with time post-injury. The injury-induced inflammatory response is
      triggered by release of alarmins, and in the present study we asked whether
      interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI.
      Here, we used samples from human TBI microdialysate, tissue sections from human
      TBI, and mouse models of central nervous system injury and found that expression
      of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum
      after 72 h in both human samples and mouse models. Astrocytes and
      oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice
      deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in
      the injured region than wild-type mice and had an altered cytokine/chemokine
      profile in response to injury. These observations indicate that IL-33 plays a
      role in neuroinflammation with microglia/macrophages being cellular targets for
      this interleukin post-TBI.

PMID- 28490278
TI  - The Perceived Experience of Children Bereaved by Parental Suicide.
AB  - Children whose parent died by suicide are a vulnerable and underserved
      population. This phenomenon will be described, as well as implications for
      practice and research. "Double Whammy," a conceptualization of the overall
      experience of this marginalized group, emerged through two in-depth interviews
      from a phenomenological qualitative study with professionals who facilitate
      support groups for children bereaved by parental suicide. It was corroborated
      with current literature and practice experiences of the authors and their
      colleagues. Stigma was the largest contributor to the "Double Whammy," and the
      following themes emerged as well: feeling isolated, feeling abandoned, and
      feeling responsible. The self-volition of suicide challenges how bereaved
      children make meaning and internalize feelings about the deceased parent, one's
      self, and others. Developmentally appropriate education about suicide grief,
      depression, and normalizing the grief process is pivotal in helping children to
      effectively cope and manage their feelings.

PMID- 28490281
TI  - Beyond Recovery.
AB  - It is a worldwide trend that more households are having pets or companion
      animals. Hence, there has been an increasing number of animal lovers experience
      companion animal loss bereavement. This form of bereavement has not been explored
      in Chinese societies. We conducted a qualitative study using in-depth interviews
      with 31 animal lovers and recruited through convenience and snowball sampling in
      Hong Kong. Companion animal loss bereavement appears to share similar features to
      other forms of bereavement but also has its unique features. The intensity of
      grief seemed to be affected by factors like the strength of the human-animal
      bond, lack of empathy from closed ones, being married without children, and
      euthanasia decision. Although the bereavement was distressful for many of our
      participants, many of them gradually achieved personal growth from their loss
      experience. We have identified seven common themes from the interview data and
      through self-reliance, social-supported, or professional-supported coping
      behaviors, people bereaved by animal loss can achieve growth from their
      experience. This study shows that postbereavement growth is possible from pet
      loss bereavement when appropriate coping strategies are adopted by the bereaved
      but some professional help may be needed.

PMID- 28490282
TI  - Death Cafe.
AB  - This article explains the meaning of the phrase Death Cafe and describes what
      typically occurs at a Death Cafe gathering. The article traces the history of the
      Death Cafe movement, explores some reasons why people take part in a Death Cafe
      gathering, and gives examples of what individuals think they might derive from
      their participation. In addition, this article notes similarities between the
      Death Cafe movement and three other developments in the field of death, dying,
      and bereavement. Finally, this article identifies two provisional lessons that
      can be drawn from Death Cafe gatherings and the Death Cafe movement itself.

PMID- 28490283
TI  - Companion Animal Death.
AB  - Human-animal relationships are increasingly incorporated into families as a
      normal part of family life. Despite this, relationships with animals are often
      viewed as inferior to human relationships. This becomes problematic during times
      of loss and grief when members of a grieving companion animal owner's support
      system do not understand the salience of the relationship with the animal.
      Veterinary and other helping professionals need basic information about the
      experience of companion animal loss in order to help support and normalize the
      experiences of grieving companion animal owners. The present study qualitatively
      describes human-animal relationships and the subsequent loss and coping
      experienced by owners of beloved companion animals. Comparison with human and
      other types of loss and factors unique to companion animal loss are discussed,
      and practical applications for veterinary and other helping professionals are
      provided.

PMID- 28490284
TI  - The Bereavement Guilt Scale.
AB  - The rationale, development, and validation of the Bereavement Guilt Scale (BGS)
      are described in this article. The BGS was based on a theoretically developed,
      multidimensional conceptualization of guilt. Part 1 describes the generation of
      the item pool, derived from in-depth interviews, and review of the scientific
      literature. Part 2 details statistical analyses for further item selection
      (Sample 1, N = 273). Part 3 covers the psychometric properties of the emergent
      BGS (Sample 2, N = 600, and Sample 3, N = 479). Confirmatory factor analysis
      indicated that a five-factor model fit the data best. Correlations of BGS scores
      with depression, anxiety, self-esteem, self-forgiveness, and mode of death were
      consistent with theoretical predictions, supporting the construct validity of the
      measure. The internal consistency and test-retest reliability were also
      supported. Thus, initial testing or examination suggests that the BGS is a valid
      tool to assess multiple components of bereavement guilt. Further psychometric
      testing across cultures is recommended.

PMID- 28490285
TI  - A comparative study of short-term outcomes of colorectal cancer surgery in the
      elderly population.
AB  - BACKGROUND: Colorectal Cancer (CRC) is a disease of the elderly, and with an
      ageing population, oncological surgical procedures for CRC in the elderly is
      expected to increase. However, the balance between surgical benefits and risks
      associated with age and comorbidities in elderly patients is obscure. MATERIALS
      AND METHODS: A retrospective database of consecutive patients who received CRC
      surgery was used to compare short-term surgical and oncological outcomes between
      patients aged >=75 and <75 years old undergoing CRC resection. RESULTS: There
      were 54 patients (63.5%) in the <75 group and 31 patients (36.5%) in the >=75
      group. Overall, there were no differences between the <75 and >=75 groups in
      postoperative HDU/ITU stay, median hospital LOS or 30-day mortality rates.
      Patients >=75 had a higher preoperative performance status (25.9% versus 71.0%, p
      < .001), but no difference in ASA Grade and referral pattern, proportion of
      emergency operations, cancer staging, resection margins, achievement of curative
      resection or median lymph node yield. There was a significantly higher use of
      adjuvant chemotherapy in the <75 age group (48.1% versus 25.8%, p = .043).
      CONCLUSIONS: With adequate patient selection, CRC resection in elderly patients
      is not associated with higher postoperative mortality or worse short-term
      oncological benefits.

PMID- 28490286
TI  - Loss of consciousness, collapse and associated driving restrictions: a
      retrospective case note review - an important reminder regarding driving
      restrictions.
AB  - Background and aims National guidelines outlining medical standards for fitness
      to drive are provided by The Driver and Vehicle Licensing Agency. We aimed to
      establish whether patients presenting with collapse or loss of consciousness
      received documented advice regarding driving restrictions, if appropriate for
      their working diagnosis. Methods and results A retrospective case note review was
      undertaken over a four-month period for emergency patients clinically coded as
      seizure/convulsion (R568) and collapse/syncope (R55X); 163 patients had a primary
      or working diagnosis on discharge that suggested driving status and restrictions
      could have been reviewed. Six groupings of diagnoses were noted, and variation
      was seen amongst documentation for each. Current driving status was documented
      for 32 patients, and 34 had restriction advice documented; 73% (119 patients) had
      further investigations or clinic review planned. Conclusion Documentation of
      driving status and restrictions is poor. This audit serves to remind clinicians
      of the importance of considering driving status when discharging patients who
      have presented with collapse or loss of consciousness. Recent high-profile media
      coverage regarding medical driving restrictions, both locally and nationally,
      have emphasised the need for knowledge of The Driver and Vehicle Licensing Agency
      guidance.

PMID- 28490287
TI  - Cheiro-oral syndrome.
AB  - We describe a 64-year-old man who presented to the emergency department with a
      two-day history of left perioral and hand numbness. Examination revealed impaired
      sensation of the left corner of the mouth and ipsilateral fingers. Neuroimaging
      showed an acute right thalamic lacunar infarct consistent with the diagnosis of
      cheiro-oral syndrome. In this report, we discuss the importance of recognising
      this syndrome and instituting appropriate management to prevent further
      cerebrovascular events.

PMID- 28490288
TI  - Reference Values of Static Balance in Spanish Preschool Children.
AB  - The purpose of this study was to examine age and sex differences in static
      balance (SB) and to determine norm-referenced values for Spanish preschool
      children. A total of 3,575 children, aged 3-6 years (age = 56.08 +/- 11.11
      months; body mass index = 15.94 +/- 1.91 kg/m2; 1,759 girls and 1,816 boys) were
      selected from 51 schools in southern Spain. To measure SB, we used the Stork
      Balance Stand Test, averaging both right and left foot data for determining SB
      normative values, expressed in percentiles. Girls exhibited a better performance
      than boys at four years of age ( p = .010, Cohen's d = -0.165), but a poorer
      performance at six years ( p = .002, Cohen's d = 0.247). SB performance of the
      entire sample was higher with increased age, except for 5-6 years.

PMID- 28490289
TI  - Combating mutations in genetic disease and drug resistance: understanding
      molecular mechanisms to guide drug design.
AB  - INTRODUCTION: Mutations introduce diversity into genomes, leading to selective
      changes and driving evolution. These changes have contributed to the emergence of
      many of the current major health concerns of the 21st century, from the
      development of genetic diseases and cancers to the rise and spread of drug
      resistance. The experimental systematic testing of all mutations in a system of
      interest is impractical and not cost-effective, which has created interest in the
      development of computational tools to understand the molecular consequences of
      mutations to aid and guide rational experimentation. Areas covered: Here, the
      authors discuss the recent development of computational methods to understand the
      effects of coding mutations to protein function and interactions, particularly in
      the context of the 3D structure of the protein. Expert opinion: While significant
      progress has been made in terms of innovative tools to understand and quantify
      the different range of effects in which a mutation or a set of mutations can give
      rise to a phenotype, a great gap still exists when integrating these predictions
      and drawing causality conclusions linking variants. This often requires a
      detailed understanding of the system being perturbed. However, as part of the
      drug development process it can be used preemptively in a similar fashion to
      pharmacokinetics predictions, to guide development of therapeutics to help guide
      the design and analysis of clinical trials, patient treatment and public health
      policy strategies.

PMID- 28490290
TI  - High confidence in falsely recognizing prototypical faces.
AB  - We applied a metacognitive approach to investigate confidence in recognition of
      prototypical faces. Participants were presented with sets of faces constructed
      digitally as deviations from prototype/base faces. Participants were then tested
      with a simple recognition task (Experiment 1) or a multiple-choice task
      (Experiment 2) for old and new items plus new prototypes, and they showed a high
      rate of confident false alarms to the prototypes. Confidence and accuracy
      relationship in this face recognition paradigm was found to be positive for
      standard items but negative for the prototypes; thus, it was contingent on the
      nature of the items used. The data have implications for lineups that employ
      match-to-suspect strategies.

PMID- 28490291
TI  - Australia's Health Care Homes: laying the right foundations.

PMID- 28490294
TI  - Failing to plan is planning to fail: advance care directives and the Aboriginal
      people of the Top End.

PMID- 28490292
TI  - Countering cognitive biases in minimising low value care.
AB  - Cognitive biases in decision making may make it difficult for clinicians to
      reconcile evidence of overuse with highly ingrained prior beliefs and intuition.
      Such biases can predispose clinicians towards low value care and may limit the
      impact of recently launched campaigns aimed at reducing such care. Commonly
      encountered biases comprise commission bias, illusion of control, impact bias,
      availability bias, ambiguity bias, extrapolation bias, endowment effects, sunken
      cost bias and groupthink. Various strategies may be used to counter such biases,
      including cognitive huddles, narratives of patient harm, value considerations in
      clinical assessments, defining acceptable levels of risk of adverse outcomes,
      substitution, reflective practice and role modelling, normalisation of deviance,
      nudge techniques and shared decision making. These debiasing strategies have
      considerable face validity and, for some, effectiveness in reducing low value
      care has been shown in randomised trials.

PMID- 28490295
TI  - Changes in medical education to help physicians meet future health care needs.

PMID- 28490296
TI  - No Jab, No Pay and vaccine refusal in Australia: the jury is out.

PMID- 28490297
TI  - A blinding eye injury caused by chasing Pokemon.

PMID- 28490298
TI  - Raccoon eyes in systemic light chain amyloidosis.

PMID- 28490299
TI  - Complicated silicosis resulting from occupational exposure to engineered stone
      products.

PMID- 28490300
TI  - The scratch test for determining the inferior hepatic margin.

PMID- 28490301
TI  - Coronary occlusion, denial and dissociation.

PMID- 28490302
TI  - Reducing the incidence of burn injuries to Indigenous Australian children.

PMID- 28490303
TI  - The frequency of eye examinations in people with diabetes.

PMID- 28490304
TI  - Indigenous and non-Indigenous Australian children hospitalised for burn injuries:
      a population data linkage study.
AB  - OBJECTIVE: To investigate differences in the characteristics of burn injuries
      leading to hospitalisation of Indigenous Australian and non-Indigenous children
      in New South Wales.Design, setting: Population-based cohort analysis of linked
      hospital and mortality data for 2000-2014. PARTICIPANTS: 35 749 Indigenous and 1
      088 938 non-Indigenous children aged 0-13 years. MAIN OUTCOME MEASURES: The
      external cause of the injury, its anatomic location, total body surface area
      affected (%TBSA), burn depth, length of hospital stay (LOS). RESULTS: 4246 non
      Indigenous and 323 Indigenous children were hospitalised for a first burn injury
      during 2000-2014. A higher proportion of Indigenous than non-Indigenous children
      were admitted with burns affecting more than 10% TBSA (17% v 12%) and a lower
      proportion of Indigenous children than of non-Indigenous children were treated at
      a hospital with a paediatric tertiary referral burn unit (40% v 50%; P < 0.001).
      The mean LOS during the index admission was almost 3 days longer for Indigenous
      children than for non-Indigenous children (6.1 days [95% CI, 4.8-7.4 days] v 3.4
      days [95% CI, 3.2-3.7 days]; P < 0.001); the difference in LOS was still
      statistically significant after adjusting for characteristics of the burn and
      residential location. CONCLUSION: The proportion of Indigenous children with
      burns who presented with burn injuries affecting more than 10% TBSA was greater
      than for non-Indigenous children. Their mean LOS was also longer; the difference
      remained statistically significant after adjusting for characteristics of the
      burn and of residential location.

PMID- 28490305
TI  - Long term risk of severe retinopathy in childhood-onset type 1 diabetes: a data
      linkage study.
AB  - OBJECTIVES: To determine the relationship between glycaemic control trajectory
      and the long term risk of severe complications in people with type 1 diabetes
      mellitus, as well as the effects of paediatric and adult HbA1c levels. DESIGN,
      SETTING, PARTICIPANTS: Data linkage study of data for adults with childhood-onset
      type 1 diabetes (diagnosed during 1975-2010) who had transitioned from paediatric
      diabetes care at the Royal Children's Hospital (Melbourne) to adult diabetes care
      at the Royal Melbourne Hospital during 1992-2013. MAIN OUTCOME MEASURES: Severe
      complications were categorised as severe diabetic retinopathy (SDR), chronic
      kidney disease, ulceration or amputation, and death. Mean HbA1c levels were
      calculated for the paediatric and adult periods. Four glycaemic control
      trajectories were defined according to mean paediatric and adult HbA1c levels:
      stable low (paediatric and adult HbA1c <= 66 mmol/mol); improving (paediatric
      HbA1c > 66 mmol/mol, adult HbA1c <= 66 mmol/mol); worsening (paediatric HbA1c <=
      66 mmol/mol, adult HbA1c > 66 mmol/mol); and stable high (paediatric and adult
      HbA1c > 66 mmol/mol). RESULTS: 503 eligible participants (253 men) were
      identified, 26 (5.2%) of whom had at least one severe complication, including 16
      with SDR (3.2%). No-one in the stable low group, but 4% of the improving, 1% of
      the worsening, and 7% of the stable high groups developed SDR. Higher mean
      paediatric (per 10.9 mmol/mol increase: odds ratio [OR], 2.9; 95% CI, 1.9-4.3; P
      < 0.01) or adult HbA1c levels (OR, 2.1; 95% CI, 1.4-3.1; P < 0.01) were
      associated with increased risk of SDR, as was longer duration of type 1 diabetes
      (per additional year: OR, 1.3; 95% CI, 1.2-1.5; P < 0.01). CONCLUSION: SDR was
      associated with higher paediatric HbA1c levels, independent of glycaemic control
      during adulthood; it was not documented in patients with a stable low glycaemic
      control trajectory.

PMID- 28490306
TI  - Adherence to diabetic eye examination guidelines in Australia: the National Eye
      Health Survey.
AB  - OBJECTIVE: To determine adherence to NHMRC eye examination guidelines for
      Indigenous and non-Indigenous Australian people with diabetes. DESIGN: Cross
      sectional survey using multistage, random cluster sampling. SETTING: Thirty
      randomly selected geographic sites in the five mainland Australian states and the
      Northern Territory, stratified by remoteness. PARTICIPANTS: 1738 Indigenous
      Australians aged 40-92 years and 3098 non-Indigenous Australians aged 50-98 years
      were recruited and examined between March 2015 and April 2016 according to a
      standardised protocol that included a questionnaire (administered by an
      interviewer) and a series of standard eye tests. MAIN OUTCOME MEASURES: Adherence
      rates to NHMRC eye examination guidelines; factors influencing adherence.
      RESULTS: Adherence to screening recommendations was significantly greater among
      non-Indigenous Australians (biennial screening; 77.5%) than Indigenous
      Australians (annual screening; 52.7%; P < 0.001). Greater adherence by non
      Indigenous Australians was associated with longer duration of diabetes (adjusted
      odds ratio [aOR], 1.19 per 5 years; P = 0.018), while increasing age was
      associated with poorer adherence in non-Indigenous Australians (aOR, 0.70 per
      decade; P = 0.011). For Indigenous Australians, residing in inner regional areas
      (aOR, 1.66; P = 0.007) and being male (aOR, 1.46; P = 0.018) were significant
      factors positively associated with adherence. CONCLUSIONS: More than three
      quarters of non-Indigenous Australians with diabetes and more than half of
      Indigenous Australians with diabetes adhere to the NHMRC eye examination
      guidelines. The discrepancy between the adherence rates may point to gaps in the
      provision or uptake of screening services in Indigenous communities, or a lack of
      awareness of the guidelines. A carefully integrated diabetic retinopathy
      screening service is needed, particularly in remote areas, to improve adherence
      rates.

PMID- 28490307
TI  - Should there be an MBS item number for advance care planning?

PMID- 28490308
TI  - Management of adverse events related to new cancer immunotherapy (immune
      checkpoint inhibitors).

PMID- 28490309
TI  - The cardiovascular research crisis and what to do about it.

PMID- 28490310
TI  - Coronary stent technology: a narrative review.

PMID- 28490311
TI  - Coronary stent technology: a narrative review.

PMID- 28490312
TI  - A positive step for pharmaceutical payment transparency.

PMID- 28490313
TI  - Radial vs Femoral Approach in Acute Coronary Syndromes: A Meta- Analysis of
      Randomized Trials.
AB  - BACKGROUND: Substantial improvements have been achieved with percutaneous
      coronary intervention (PCI) for the treatment of Acute Coronary Syndromes (ACS).
      Nevertheless, bleeding still affects outcomes. The radial approach for PCI has
      shown important benefits on access site complications, but is still not achieving
      universal consensus as first choice in acute settings. Therefore, we performed a
      comprehensive meta-analysis of randomized trials comparing radial vs femoral
      approach in PCI for ACS. METHODS: The literature and main scientific session
      abstracts were scanned for randomized studies comparing radial vs femoral
      approach for PCI in ACS. Primary endpoint was mortality within 30-days. Secondary
      endpoints were: 1) Major Adverse Cardiovascular Events (MACE), 2) major bleeding,
      and, 3) vascular complications. RESULTS: We included 17 randomized trials,
      enrolling 19325 patients. A total of 9635 patients were randomized to the radial
      approach and 9690 to the femoral approach. The radial approach was associated
      with a significant reduction in mortality (1.8 vs 2.5%, odds ratio, OR [95% CI] =
      0.72 [0.59,0.88], p = 0.001, pheterogeneity = 0.31) and in major bleeding
      complications compared with the femoral approach (1.5 vs 2.6%, OR [95% CI] = 0.57
      [0.47, 0.71], p < 0.00001, pheterogeneity = 0.59), with similar advantages
      observed for both ST-elevation myocardial infarction and non-ST segment elevation
      ACS. MACE occurrence and vascular complications were also reduced with the radial
      approach (OR [95% CI] = 0.82 [0.74, 0.92], p = 0.0005, and OR [95% CI] = 0.52
      [0.47, 0.58], p < 0.00001, respectively). Our results were not influenced by
      patient risk profile or the antithrombotic strategy applied. CONCLUSION: Our meta
      analysis shows that among ACS patients undergoing PCI, the radial approach is
      associated with a significant reduction in mortality, major bleeding
      complications, MACE and vascular complication compared with the femoral approach.

PMID- 28490314
TI  - Pain Experience in Dementia Subtypes: A Systematic Review.
AB  - Recently, the number of studies focusing on pain in dementia has increased
      considerably. Still, little attention has been paid to the influence of the
      neuropathology of different dementia subtypes on pain experience. In 2003, a
      review identified several studies that indicated a relation between dementia
      subtype and pain experience. Now, ten years later, an update is warranted. We
      conducted a systematic review to identify studies that assessed pain experience
      and dementia subtypes by searching PubMed, Embase, PsycINFO, CINAHL, and Cochrane
      Library. Inclusion criteria were: (1) major dementia subtype diagnosis i.e.
      Alzheimer's dementia (AD), vascular dementia (VaD), frontotemporal dementia
      (FTD), dementia with Lewy Bodies (DLB); (2) age >=60 years; and (3) pain
      experience. We identified twelve studies that addressed AD, three studies VaD,
      one study FTD, and no studies DLB. In AD, studies on clinical pain indicate a
      reduced pain experience compared to controls, whereas experimental studies show
      inconsistent findings. In VaD, clinical studies found that primary caregivers
      rated pain equal to cognitively intact controls, although more painful locations
      were reported. During self-report, elderly with VaD reported higher pain levels
      than cognitively intact controls. In FTD, a significantly lower pain sensitivity
      to experimental pain was found. Considering the limited number of studies, these
      findings should be considered with caution. Existing literature provides some
      evidence that dementia subtype affects pain experience. Further research is
      needed to clarify the relation between dementia subtype and pain experience as it
      could serve as basis for improving the assessment and management of pain in
      people with dementia.

PMID- 28490315
TI  - Orofacial Pain and Mastication in Dementia.
AB  - Orofacial pain is a common condition in the general population. It is likely that
      this is also the case in older persons with a dementia. However, the assessment
      of (orofacial) pain in non-verbal individuals is hampered by the subjective
      nature of pain, and their limited communicative abilities. To overcome this
      drawback, several tools have been developed for the assessment of pain based on
      observations of pain-specific facial activities, body movements, and
      vocalizations. Unfortunately, none of the so far developed observational tools
      have been designed specifically for the assessment of orofacial pain. While the
      recent psychometric testing of the Orofacial MOBID Pain Scale did not yield
      reliable outcomes, the subsequently developed Orofacial Pain Scale for Non-Verbal
      Individuals (OPS-NVI) is currently being evaluated and shows good promise to be
      reliable and valid. Besides the assessment of orofacial pain, an important
      application of this instrument will be the investigation of the probable causal
      association between impaired chewing and cognitive decline, in which orofacial
      pain plays a mediating role by its negative influence on chewing ability. The
      identification of this negative influence will urge opinion leaders and policy
      makers to improve the oral health status in older persons with a dementia.
      Ultimately, pain-free oral functioning may lead to a higher quality of life and
      might help stabilizing or improving cognition in this frail and vulnerable
      patient population.

PMID- 28490316
TI  - Incidence and comparison of retrospective and prospective data on respiratory and
      gastrointestinal infections in German households.
AB  - BACKGROUND: Acute respiratory infections (ARI) and acute gastrointestinal
      infections (AGI) are the most common childhood infections, and corresponding data
      can either be collected prospectively or retrospectively. The aim of this study
      was to estimate the incidence of respiratory and gastrointestinal episodes in
      German households with children attending day care and to compare results of
      prospective and retrospective data collection. METHODS: We conducted a 4 months
      prospective cohort study in the winter period 2014/2015 and recruited parents of
      children aged 0-6 years in 75 day care centers in Braunschweig, Lower Saxony,
      Germany. For all household members, we collected information on episodes of ARI
      and AGI. We applied prospective data collection in one study arm and
      retrospective data collection with a reporting period of 2 months in the other.
      Poisson regression was used to model monthly incidence rates for both study arms.
      RESULTS: In total, 100 households (including 404 persons) participated in the
      retrospective group and 77 households (282 persons) in the prospective group.
      Incidence estimates for ARI (retrospective group: 0.52 per person month,
      prospective group: 0.47) were higher than for AGI (retrospective group: 0.14,
      prospective group: 0.13). The adjusted incidence estimates were similar in both
      study arms for ARI (incidence rate ratio for retrospective versus prospective
      data collection: 1.11 [confidence interval (CI) 95% 0.99; 1.24], p = 0.42) as
      well as for AGI (1.10 [CI 95% 0.89; 1.37], p = 0.27). CONCLUSION: If there is no
      need to collect biomaterials or data on severity of the diseases, incidence of
      infections in the household setting over a short time period (2 months) can be
      assessed retrospectively.

PMID- 28490317
TI  - Measured, opportunistic, unexpected and naive quitting: a qualitative grounded
      theory study of the process of quitting from the ex-smokers' perspective.
AB  - BACKGROUND: To better understand the process of quitting from the ex-smokers'
      perspective, and to explore the role spontaneity and planning play in quitting.
      METHODS: Qualitative grounded theory study using in-depth interviews with 37
      Australian adult ex-smokers (24-68 years; 15 males, 22 females) who quit smoking
      in the past 6-24 months (26 quit unassisted; 11 used assistance). RESULTS: Based
      on participants' accounts of quitting, we propose a typology of quitting
      experiences: measured, opportunistic, unexpected and naive. Two key features
      integral to participants' accounts of their quitting experiences were used as the
      basis of the typology: (1) the apparent onset of quitting (gradual through to
      sudden); and (2) the degree to which the smoker appeared to have prepared for
      quitting (no evidence through to clear evidence of preparation). The resulting 2
      * 2 matrix of quitting experiences took into consideration three additional
      characteristics: (1) the presence or absence of a clearly identifiable trigger;
      (2) the amount of effort (cognitive and practical) involved in quitting; and (3)
      the type of cognitive process that characterised the quitting experience
      (reflective; impulsive; reflective and impulsive). CONCLUSIONS: Quitting
      typically included elements of spontaneity (impulsive behaviour) and preparation
      (reflective behaviour), and, importantly, the investment of time and cognitive
      effort by participants prior to quitting. Remarkably few participants quit
      completely out-of-the-blue with little or no preparation. Findings are discussed
      in relation to stages-of-change theory, catastrophe theory, and dual process
      theories, focusing on how dual process theories may provide a way of
      conceptualising how quitting can include elements of both spontaneity and
      preparation.

PMID- 28490318
TI  - Integrated mRNA and microRNA transcriptome variations in the multi-tepal mutant
      provide insights into the floral patterning of the orchid Cymbidium goeringii.
AB  - BACKGROUND: Cymbidium goeringii is a very famous traditional orchid plant in
      China, which is well known for its spectacular and diverse flower morphology. In
      particular, the multi-tepal mutants have considerable ecological and cultural
      value. However, the current understanding of the molecular mechanisms of floral
      patterning and multi-tepal development is limited. In this study, we performed
      expression profiling of both microRNA (miRNA) and mRNA from wild-type and typical
      multi-tepal-mutant flowers of C. goeringii for the first time, to identify the
      genes and pathways regulating floral morphogenesis in C. goeringii. RESULTS:
      Total clean reads of 98,988,774 and 100,188,534 bp were obtained from the wild
      type and mutant library, respectively, and de novo assembled into 98,446
      unigenes, with an average length of 989 bp. Among them, 18,489 were identified as
      differentially expressed genes between the two libraries according to comparative
      transcript profiling. The majority of the gene ontology terms and Kyoto
      Encyclopedia of Genes and Genomes pathway enrichment responses were for membrane
      building and ploidy-related processes, consistent with the excessive floral
      organs and altered cell size observed in the mutant. There were 29 MADS-box
      genes, as well as a large number of floral-related regulators and hormone
      responsive genes, considered as candidates regulating floral patterning of C.
      goeringii. Small RNA sequencing revealed 132 conserved miRNA families expressed
      in flowers of C. goeringii, and 11 miRNAs corresponding to 455 putative target
      genes were considered to be responsible for multi-tepal development. Importantly,
      integrated analysis of mRNA and miRNA sequencing data showed two transcription
      factor/microRNA-based genetic pathways contributing to the multi-tepal trait:
      well-known floral-related miR156/SPL and miR167/ARF regulatory modes involved in
      reproductive organ development; and the miR319/TCP4-miR396/GRF regulatory cascade
      probably regulating cell proliferation of the multi-tepal development.
      CONCLUSIONS: Integrated mRNA and miRNA profiling data provided comprehensive gene
      expression information on the wild-type and multi-tepal mutant at the
      transcriptional level that could facilitate our understanding of the molecular
      mechanisms of floral patterning of C. goeringii. These data could also be used as
      an important resource for investigating the genetics of floral morphogenesis and
      various biological mechanisms of orchid plants.

PMID- 28490319
TI  - Prediction of gene expression with cis-SNPs using mixed models and regularization
      methods.
AB  - BACKGROUND: It has been shown that gene expression in human tissues is heritable,
      thus predicting gene expression using only SNPs becomes possible. The prediction
      of gene expression can offer important implications on the genetic architecture
      of individual functional associated SNPs and further interpretations of the
      molecular basis underlying human diseases. METHODS: We compared three types of
      methods for predicting gene expression using only cis-SNPs, including the
      polygenic model, i.e. linear mixed model (LMM), two sparse models, i.e. Lasso and
      elastic net (ENET), and the hybrid of LMM and sparse model, i.e. Bayesian sparse
      linear mixed model (BSLMM). The three kinds of prediction methods have very
      different assumptions of underlying genetic architectures. These methods were
      evaluated using simulations under various scenarios, and were applied to the
      Geuvadis gene expression data. RESULTS: The simulations showed that these four
      prediction methods (i.e. Lasso, ENET, LMM and BSLMM) behaved best when their
      respective modeling assumptions were satisfied, but BSLMM had a robust
      performance across a range of scenarios. According to R 2 of these models in the
      Geuvadis data, the four methods performed quite similarly. We did not observe any
      clustering or enrichment of predictive genes (defined as genes with R 2 >= 0.05)
      across the chromosomes, and also did not see there was any clear relationship
      between the proportion of the predictive genes and the proportion of genes in
      each chromosome. However, an interesting finding in the Geuvadis data was that
      highly predictive genes (e.g. R 2 >= 0.30) may have sparse genetic architectures
      since Lasso, ENET and BSLMM outperformed LMM for these genes; and this
      observation was validated in another gene expression data. We further showed that
      the predictive genes were enriched in approximately independent LD blocks.
      CONCLUSIONS: Gene expression can be predicted with only cis-SNPs using well
      developed prediction models and these predictive genes were enriched in some
      approximately independent LD blocks. The prediction of gene expression can shed
      some light on the functional interpretation for identified SNPs in GWASs.

PMID- 28490320
TI  - Astaxanthin protects astrocytes against trauma-induced apoptosis through
      inhibition of NKCC1 expression via the NF-kappaB signaling pathway.
AB  - BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic
      pharmacological properties that is seen as a possible drug for treating cerebral
      ischemic injury and subarachnoid hemorrhage. Na+-K+-2Cl- co-transporter-1
      (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated
      by various insults, leading to the formation of cell swelling and brain edema. We
      previously established that ATX attenuated brain edema and improved neurological
      outcomes by modulating NKCC1 expression after traumatic brain injury in mice.
      This paper explored the molecular mechanism of ATX-mediated inhibition of NKCC1
      utilizing an in vitro astrocyte stretch injury model. RESULTS: Stretch injury in
      cultured astrocytes lowered cell viability time-dependently, which was
      substantially reducing by pretreating with ATX (50 MUmol/L). Stretch injury
      increased Bax level and cleaved caspase-3 activity, and decreased Bcl-2 level and
      pro-caspase 3 activity, resulting in the apoptosis of astrocytes. Additionally,
      stretch injury substantially raised the gene and protein expressions of
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha and prompted
      the expression and nuclear translocation of NF-kappaB. Pretreatment with ATX
      remarkably prevented the trauma-induced initiation of NF-kappaB, expressions of
      pro-inflammatory cytokines, and cell apoptosis. Moreover, stretch injury markedly
      elevated the gene and protein expression of NKCC1, which was partly blocked by co
      treatment with ATX (50 umol/L) or an NF-kappaB inhibitor (PDTC, 10 umol/L).
      Cleaved caspase-3 activity was partially reduced by PDTC (10 umol/L) or an NKCC1
      inhibitor (bumetanide, 50 umol/L). CONCLUSIONS: ATX attenuates apoptosis after
      stretch injury in cultured astrocytes by inhibiting NKCC1 expression, and it acts
      by reducing the expression of NF-kappaB-mediated pro-inflammatory factors.

PMID- 28490321
TI  - Transabdominal Preperitoneal (TAPP) versus Lichtenstein operation for primary
      inguinal hernia repair - A systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Transabdominal Preperitoneal (TAPP) and Lichtenstein operation are
      established methods for inguinal hernia repair in clinical practice. Meta
      analyses of randomized controlled studies, comparing those two methods for repair
      of primary inguinal hernia, are still missing. In this study, a systematic review
      and meta-analysis of published randomized controlled trials was performed to
      compare early and long term outcomes of the two methods. METHODS: A literature
      search was carried out to identify randomized controlled trials, which compared
      TAPP and Lichtenstein repair for primary inguinal hernia. Outcome measures
      included duration of operation, length of hospital stay, acute postoperative and
      chronic pain, time to return to work, hematoma, wound infection, neuralgia,
      numbness, scrotal swelling, seroma and hernia recurrence. A quantitative meta
      analysis was performed, using Odds Ratios (OR) or Standardized Mean Difference
      (SMD), and Confidence Interval (CI). RESULTS: Eight controlled randomized studies
      were identified suitable for the analysis. The mean duration of the operation was
      shorter in Lichtenstein repair (SMD = 6.79 min, 95% CI, -0.68 - 14.25), without
      significant difference. Comparing both techniques, patients of the laparoscopic
      group showed postoperatively significantly less chronic inguinal pain (OR = 0.42;
      95% CI, 0.23-0.78). Analyses of the remaining outcome measures did not show any
      significant differences between the two techniques. CONCLUSION: The results of
      this analysis indicate that complication rate and outcome of both procedures are
      comparable. TAPP operation demonstrated only one advantage over Lichtenstein
      operation with significantly less chronic inguinal pain postoperatively.

PMID- 28490322
TI  - The effects of video game therapy on balance and attention in chronic ambulatory
      traumatic brain injury: an exploratory study.
AB  - BACKGROUND: Patients with traumatic brain injury often have balance and attentive
      disorders. Video game therapy (VGT) has been proposed as a new intervention to
      improve mobility and attention through a reward-learning approach. In this pilot
      randomized, controlled trial, we tested the effects of VGT, compared with a
      balance platform therapy (BPT), on balance, mobility and selective attention in
      chronic traumatic brain injury patients. METHODS: We enrolled chronic traumatic
      brain injury patients (n = 21) that randomly received VGT or BPT for 3 sessions
      per week for 6 weeks. The clinical outcome measures included: i) the Community
      Balance & Mobility Scale (CB&M); ii) the Unified Balance Scale (UBS); iii) the
      Timed Up and Go test (TUG); iv) static balance and v) selective visual attention
      evaluation (Go/Nogo task). RESULTS: Both groups improved in CB&M scores, but only
      the VGT group increased on the UBS and TUG with a between-group significance (p <
      0.05). Selective attention improved significantly in the VGT group (p < 0.01).
      CONCLUSIONS: Video game therapy is an option for the management of chronic
      traumatic brain injury patients to ameliorate balance and attention deficits.
      TRIAL REGISTRATION: NCT01883830 , April 5 2013.

PMID- 28490323
TI  - Lifetime prevalence of mental disorders among first and second generation
      individuals with Turkish migration backgrounds in Germany.
AB  - BACKGROUND: This paper focuses on the lifetime prevalence of mental disorders in
      individuals with Turkish migration backgrounds in Germany, as there is a lack of
      reliable epidemiological data on this subject. METHODS: In total, 662 adults with
      Turkish migration backgrounds were interviewed in Hamburg and Berlin by trained,
      bilingual interviewers using the computerized Composite International Diagnostic
      Interview (CIDI DIA-X Version 2.8) to assess diagnoses according to the DSM-IVTR.
      RESULTS: The analyses showed a weighted lifetime prevalence of 78.8% for any
      mental disorder, 21.6% for more than one and 7.3% for five or more disorders. Any
      mood disorder (41.9%), any anxiety disorder (35.7%) and any somatoform
      disorder/syndrome (33.7%) had the highest prevalences. Despite the
      sociodemographic differences between the first and second generations, there were
      no significant differences in the lifetime prevalence between generations, with
      the exception of any bipolar disorder. Female gender, older age and no current
      partnership were significantly associated with the occurrence of any mood
      disorder. CONCLUSIONS: Overall, the results indicate a high lifetime prevalence
      in individuals with Turkish migration backgrounds in Germany. These initial data
      are highly relevant to the German clinical and psychosocial healthcare system;
      however, the methodological limitations and potential biases should be considered
      when interpreting the results.

PMID- 28490324
TI  - The experiences of attempt survivor families and how they cope after a suicide
      attempt in Ghana: a qualitative study.
AB  - BACKGROUND: Ghana's socio-cultural landscape proscribes suicidal behaviour, and
      this has serious ramifications for attempt survivors and their families. The
      objective of this qualitative study was to understand the experiences of the
      families of attempt survivors and how they cope with the aftermath of the
      attempt. METHODS: Ten families with attempted suicides agreed to participate in
      the study, hence they were interviewed. The information gathered was manually
      analyzed according to Interpretative Phenomenological Analysis (IPA) resulting in
      three major thematic areas. RESULTS: Three major themes emerged two of which
      addressed negative experiences and reactions towards the attempts: Experiencing
      shame and stigma, and Reactive affect. The third theme addressed the coping
      resources of these informants under the theme: Surviving the stress of attempt.
      The specific coping resources included personalized spiritual coping, social
      support, and avoidance. CONCLUSIONS: Family systems theory is used to explain
      some of the findings of this study, and the implication for clinical practice and
      designing postvention programs for families after a suicide attempt are
      addressed.

PMID- 28490325
TI  - Reaching beyond the review of research evidence: a qualitative study of decision
      making during the development of clinical practice guidelines for disease
      prevention in healthcare.
AB  - BACKGROUND: The judgment and decision making process during guideline development
      is central for producing high-quality clinical practice guidelines, but the topic
      is relatively underexplored in the guideline research literature. We have studied
      the development process of national guidelines with a disease-prevention scope
      produced by the National board of Health and Welfare (NBHW) in Sweden. The NBHW
      formal guideline development model states that guideline recommendations should
      be based on five decision-criteria: research evidence; curative/preventive effect
      size, severity of the condition; cost-effectiveness; and ethical considerations.
      A group of health profession representatives (i.e. a prioritization group) was
      assigned the task of ranking condition-intervention pairs for guideline
      recommendations, taking into consideration the multiple decision criteria. The
      aim of this study was to investigate the decision making process during the two
      year development of national guidelines for methods of preventing disease.
      METHODS: A qualitative inductive longitudinal case study approach was used to
      investigate the decision making process. Questionnaires, non-participant
      observations of nine two-day group meetings, and documents provided data for the
      analysis. Conventional and summative qualitative content analysis was used to
      analyse data. RESULTS: The guideline development model was modified ad-hoc as the
      group encountered three main types of dilemmas: high quality evidence vs. low
      adoptability of recommendation; insufficient evidence vs. high urgency to act;
      and incoherence in assessment and prioritization within and between four
      different lifestyle areas. The formal guideline development model guided the
      decision-criteria used, but three new or revised criteria were added by the
      group: 'clinical knowledge and experience', 'potential guideline consequences'
      and 'needs of vulnerable groups'. The frequency of the use of various criteria in
      discussions varied over time. Gender, professional status, and interpersonal
      skills were perceived to affect individuals' relative influence on group
      discussions. CONCLUSIONS: The study shows that guideline development groups make
      compromises between rigour and pragmatism. The formal guideline development model
      incorporated multiple aspects, but offered few details on how the different
      criteria should be handled. The guideline development model devoted little
      attention to the role of the decision-model and group-related factors. Guideline
      development models could benefit from clarifying the role of the group-related
      factors and non-research evidence, such as clinical experience and ethical
      considerations, in decision-processes during guideline development.

PMID- 28490326
TI  - The clinical epidemiology of fatigue in newly diagnosed heart failure.
AB  - BACKGROUND: Fatigue is a common and distressing but poorly understood symptom
      among patients with heart failure (HF). This study sought to evaluate the
      prevalence, predictors, and prognostic value of clinically documented fatigue in
      newly diagnosed HF patients from the community. METHODS: This retrospective
      cohort study consisted of 12,285 newly diagnosed HF patients receiving health
      care services through the Geisinger Health System, with passive data collection
      through electronic medical records (EMR). Incident HF, fatigue, and other study
      variables were derived from coded data within EMRs. A collection of 87 candidate
      predictors were evaluated to ascertain the strongest independent predictors of
      fatigue using logistic regression. Patients were followed for all-cause mortality
      for an average of 4.8 years. The associations between fatigue and 6-month, 12
      month, and overall mortality were evaluated via Cox proportional hazards
      regression models. RESULTS: Clinically documented fatigue was found in 4827 (39%)
      newly diagnosed HF patients. Depression demonstrated the strongest association
      with fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms
      including dyspnea, chest pain, edema, syncope, and palpitations were significant
      predictors of fatigue. Volume depletion, lower body mass index, and abnormal
      weight loss were also strong predictors of fatigue. Fatigue was not significantly
      associated with either 6-month (HR = 1.12, p = 0.16) or overall mortality (HR =
      1.00, p = 0.89) in adjusted models. CONCLUSIONS: Fatigue is a commonly documented
      symptom among newly diagnosed HF patients, and its origins may lie in both
      psychologic and physiologic factors. Though fatigue did provide a prognostic
      signal in the short-term, this was largely explained by physiologic confounders.
      Proper therapeutic remediation of fatigue in HF relies on identifying underlying
      factors.

PMID- 28490327
TI  - The impact of income inequality and national wealth on child and adolescent
      mortality in low and middle-income countries.
AB  - BACKGROUND: Income inequality and national wealth are strong determinants for
      health, but few studies have systematically investigated their influence on
      mortality across the early life-course, particularly outside the high-income
      world. METHODS: We performed cross-sectional regression analyses of the
      relationship between income inequality (national Gini coefficient) and national
      wealth (Gross Domestic Product (GDP) averaged over previous decade), and all
      cause and grouped cause national mortality rate amongst infants, 1-4, 5-9, 10-14,
      15-19 and 20-24 year olds in low and middle-income countries (LMIC) in 2012. Gini
      models were adjusted for GDP. RESULTS: Data were available for 103 (79%)
      countries. Gini was positively associated with increased all-cause and
      communicable disease mortality in both sexes across all age groups, after
      adjusting for national wealth. Gini was only positively associated with increased
      injury mortality amongst infants and 20-24 year olds, and increased non
      communicable disease mortality amongst 20-24 year old females. The strength of
      these associations tended to increase during adolescence. Increasing GDP was
      negatively associated with all-cause, communicable and non-communicable disease
      mortality in males and females across all age groups. GDP was also associated
      with decreased injury mortality in all age groups except 15-19 year old females,
      and 15-24 year old males. GDP became a weaker predictor of mortality during
      adolescence. CONCLUSION: Policies to reduce income inequality, rather than
      prioritising economic growth at all costs, may be needed to improve adolescent
      mortality in low and middle-income countries, a key development priority.

PMID- 28490328
TI  - Process evaluation of an interorganizational cooperation initiative in vocational
      rehabilitation: the Dirigo project.
AB  - BACKGROUND: This study analyzes the process of establishing and developing a
      cooperative vocational rehabilitation project with special focus on
      organizational and professional aspects. In the project, officials from the
      Swedish Social Insurance Agency and the Swedish Public Employment Service worked
      cooperatively with participants on long-term sick leave, youths with disability
      benefits, and people receiving social allowances. The officials used Motivational
      Interviewing (MI) as a method when meeting participants, and were able to offer
      flexible and tailored case management. The goal was to improve work ability and
      promote self-sufficiency. METHODS: The process evaluation was carried out through
      continuous data collection throughout the project (2012-2014), resulting in a
      total of 28 individual interviews and 17 focus groups with officials and
      managers. The material was categorized through an inductive content analysis, and
      analyzed using social capital as a theoretical frame. RESULTS: The evaluation
      points to how issues related to design, organization and management contributed
      to the project not reaching its goals, e.g. problems with recruitment of
      participants, the funding structure, and staffing problems on the managerial
      level. Still, officials reported positive effects of close cooperation, which was
      perceived as facilitating the case management by fostering a mutual understanding
      and access to resources and rehabilitation measures from more than one authority.
      CONCLUSIONS: Cooperative work combined with the use of MI and flexible case
      management seem to promote an increased trust between officials from different
      authorities and participants, which in the study is conceptualized as bonding and
      bridging social capital (between officials) and linking social capital (between
      officials and participants). The organizational problems combined with the
      relatively large differences in approaches between the project and regular
      practice obstructed implementation, where the authorities involved did not appear
      to be ready for implementing methodologies that require organizational
      restructuring.

PMID- 28490329
TI  - Directed evolution and secretory expression of a pyrethroid-hydrolyzing esterase
      with enhanced catalytic activity and thermostability.
AB  - BACKGROUND: Pyrethroids are potentially harmful to human health and ecosystems.
      It is necessary to develop some efficient strategies to degrade pyrethroid
      residues. Biodegradation is generally considered as a safe, efficient, and
      inexpensive way to eliminate environmental contaminants. To date, although
      several pyrethroid-hydrolyzing esterases have been cloned, there has been no
      report about a pyrethroid hydrolase with high hydrolytic activity, good
      stability, and high productivity, indispensable enzymatic properties in practical
      biodegradation. Almost all pyrethroid hydrolases are intracellular enzymes, which
      require complex extraction protocols and present issues in terms of easy
      inactivation and low production. RESULTS: In this study, random mutagenesis was
      performed on one pyrethroid-hydrolyzing esterase, Sys410, to enhance its activity
      and thermostability. Two beneficial mutations, A171V and D256N, were obtained by
      random mutagenesis and gave rise to the mutant M2. The mutant displayed ~1.5-fold
      improvement in the kcat/Km value and 2.46-fold higher catalytic activity. The
      optimal temperature was 10  degrees C higher than that of the wild-type enzyme
      (55  degrees C). The half-life at 40-65  degrees C was 3.3-310 times longer. It
      was surprising that M2 has a half-life of 12 h at 70  degrees C while Sys410 was
      completely inactivated at 70  degrees C. In addition, the desired gene was
      extracellularly expressed in a Pichia pastoris host system. The soluble
      expression level reached up to 689.7 mg/L. Remarkably, the enzyme could
      efficiently degrade various pyrethroids at moderate temperature for 15 min,
      exceeding a hydrolysis rate of 98%, which is the highest value ever reported.
      CONCLUSIONS: This is the first report about random mutagenesis and secretory
      expression of pyrethroid-hydrolyzing esterase with high-level productivity and
      purity in P. pastoris. Broad substrate specificity, enhanced activity and
      thermostability make M2 an ideal candidate for the biodegradation of pyrethroid
      residues.

PMID- 28490330
TI  - Comparative measurements of bone mineral density and bone contrast values in
      canine femora using dual-energy X-ray absorptiometry and conventional digital
      radiography.
AB  - BACKGROUND: Aseptic loosening due to bone remodelling processes after total hip
      replacement is one common cause for revision surgery. In human medicine, dual
      energy X-ray absorptiometry (DEXA) is the gold standard for quantitative
      evaluation of bone mineral density, whereas in veterinary medicine conventional
      radiography is used for follow-up studies. Recently, a method has been described
      using digital X-ray images for quantitative assessment of grey scale values of
      bone contrast. Therefore, the aim of the present study was to evaluate the
      correlation of bone mineral density (BMD) measured by DEXA with grey scale values
      (GV) measured in digital X-ray images (RX50, RX66) ex vivo. RESULTS: The measured
      GV in the chosen X-ray settings showed on average a good correlation (r = 0.61)
      to the measured BMD with DEXA. Correlation between the two X-ray settings was
      very good (r = 0.81). For comparisons among regions of interests (ROIs) a
      difference of 8.2% was found to be statistically significant, whereas in the case
      of RX50 and RX66 differences of 5.3% and 4.1% were found to be statistically
      significant. CONCLUSIONS: Results indicate that measuring absolute changes in
      bone mineral density might be possible using digital radiography. Not all
      significant differences between ROIs detectable with DEXA can be displayed in the
      X-ray images because of the lower sensitivity of the radiographs. However, direct
      comparison of grey scale values of the periprosthetic femur in one individual
      patient during the follow-up period, in order to predict bone remodelling
      processes, should be possible, but with a lesser sensitivity than with DEXA. It
      is important that the same X-ray settings are chosen for each patient for follow
      up studies.

PMID- 28490331
TI  - Quantifying capture stress in free ranging European roe deer (Capreolus
      capreolus).
AB  - BACKGROUND: To understand and reduce the concomitant effects of trapping and
      handling procedures in wildlife species, it is essential to measure their
      physiological impact. Here, we examined individual variation in stress levels in
      non-anesthetized European roe deer (Capreolus capreolus), which were captured in
      box traps and physically restrained for tagging, biometrics and bio-sampling. In
      winter 2013, we collected venous blood samples from 28 individuals during 28
      capture events and evaluated standard measurements for stress (heart rate, body
      temperature, neutrophil to lymphocyte ratio, lactate and total cortisol).
      Additionally, we assessed stress using the immunological tool, Leukocyte Coping
      Capacity (LCC), a real-time proxy for stress measuring oxygen radical production
      by leukocytes. Finally, the behavioral response to handling was recorded using a
      scoring system. RESULTS: LCC and therefore stress levels were negatively
      influenced by the time animals spent in the box trap with human presence at the
      capture site prior to handling. In contrast, none of the classical stress
      measures, including total cortisol, nor the behavioral assessment, were
      correlated with the stressor tested (time of human presence prior to handling)
      and thus did not provide a clear depiction regarding the extent of the animals
      short-term stress response. CONCLUSIONS: Overall our study verifies the LCC as a
      strong method to quantify short-term stress reactions in wildlife. Moreover, our
      results clearly show that human presence at the trapping site prior to handling
      should be kept to an absolute minimum in order to reduce stress levels.

PMID- 28490332
TI  - Feasibility of the Participation and Activity Inventory for Children and Youth
      (PAI-CY) and Young Adults (PAI-YA) with a visual impairment: a pilot study.
AB  - BACKGROUND: Having a visual impairment affects quality of life, daily functioning
      and participation. To assess rehabilitation needs of visually impaired children
      and young adults, the Participation and Activity Inventory for Children and Youth
      (PAI-CY) and Young Adults (PAI-YA) were developed. The PAI-CY comprises four
      questionnaires for different age categories: 0-2 years, 3-6 years, 7-12 years and
      13-17 years. This pilot study assesses the feasibility and acceptability of the
      PAI-CY and PAI-YA, and the relevance of the content of the questionnaires.
      METHODS: In addition to the regular admission procedure, the PAI-CY and PAI-YA
      were completed by 30 participants (six per questionnaire). For the PAI-CY,
      parents completed the questionnaire online prior to admission. From age 7 years
      onwards, children completed the questionnaire face-to-face with a rehabilitation
      professional during the admission procedure. Young adults completed the PAI-YA
      online. Subsequently, participants and professionals administered an evaluation
      form. RESULTS: Overall, 85% of the parents rated all aspects of the PAI-CY
      neutral to positive, whereas 100% of all children and young adults were neutral
      to positive on all aspects, except for the duration to complete. The main
      criticism of professionals was that they were unable to identify actual
      rehabilitation needs using the questionnaires. Minor adjustments were recommended
      for the content of questions. CONCLUSIONS: Parents, children and young adults
      were mostly satisfied with the questionnaires, however, professionals suggested
      some changes. The adaptations made should improve satisfaction with content,
      clarification of questions, and satisfaction with the questionnaires in compiling
      a rehabilitation plan. Although face and content validity has been optimized, a
      larger field study is taking place to further develop and evaluate the
      questionnaires.

PMID- 28490333
TI  - Micronutrient powders to combat anemia in young children: does it work?
AB  - In developing countries, anemia and iron deficiency in early childhood are two
      highly prevalent public health problems. Providing caregivers with a powder
      containing multiple vitamins and minerals (also known as micronutrient powder or
      MNP) as a food supplement is a widely used strategy to combat these problems.
      However, concerns exist around MNP programs with regards to effectiveness and
      potential negative impact on diarrheal disease prevalence and gut flora. Teshome
      et al. (BMC Medicine 15:89, 2017) recently tested a MNP with a new iron
      formulation, iron-EDTA, which has a potentially higher bioavailability and thus
      requires a lower iron content. Nevertheless, neither the new formulation nor the
      standard formulation decreased anemia prevalence as compared to a control MNP
      without iron. However, in all groups, anemia prevalence was reduced after 30 days
      of intervention, and iron deficiency prevalence was significantly lower in
      children receiving iron-EDTA, showing that the new formulation holds promise.
      More research is needed to verify whether the lower iron content of these MNPs
      can also reduce the prevalence of associated side effects.Please see related
      article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0839-z
      .

PMID- 28490334
TI  - HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by
      enhancing MYC activity.
AB  - BACKGROUND: Hematological and neurological expressed 1 (HN1) is upregulated in
      many tumors, but the role of HN1 in breast cancer progression and its regulatory
      mechanism have not been well understood. METHODS: To study the role of HN1 in the
      initiation and progression of breast cancer, we examined HN1 levels in breast
      cancer cells and tissues and analyzed the relationship between HN1 levels and
      patient survival. We used mammosphere formation assay, side population analysis,
      wound healing assay, transwell assay, soft agar formation assay, and xenografted
      tumor model to determine the effect of HN1 on the expansion of breast cancer stem
      cells, and the migration, invasion and tumorigenesis of breast cancer. To
      determine whether HN1 regulates MYC, we used quantitative real-time PCR and
      Western blot analysis to assess the expression of MYC and their targeted genes to
      determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1
      overexpression. RESULTS: In this study, we found that HN1 was upregulated in
      breast cancer tissues. Patients with high levels of HN1 expression had
      significantly shorter survival than those with low HN1 expression. In breast
      cancer cell line, ectopic overexpression of HN1 not only promoted the expansion
      of breast cancer stem cells, but also promoted cell migration, invasion, and
      tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there
      was a positive correlation between MYC (also known as c-MYC) level and HN1 level,
      mechanism analysis suggested HN1 promoted the expression of MYC and its targeted
      genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the
      effect of HN1 overexpression in breast cancer cell lines. CONCLUSION: Taken
      together, these data reveal that HN1 promotes the progression of breast cancer by
      upregulating MYC expression, and might be a therapeutic target for breast cancer.

PMID- 28490335
TI  - ING5 suppresses breast cancer progression and is regulated by miR-24.
AB  - BACKGROUND: The inhibitor of growth (ING) gene family of tumor suppressors is
      involved in multiple cellular functions such as cell cycle regulation, apoptosis,
      and chromatin remodeling. ING5 is a new member of the ING family whose function
      and regulation remain largely unknown. METHODS: Quantitative real-time PCR and
      western blot were used to examine the expression levels of ING5 in breast cancer
      tissues. The miRNAs that potentially targeted ING5 were determined by
      bioinformatics analysis and luciferase reporter assay. Cell viability assay,
      transwell invasion and apoptosis assay were used to characterize the changes
      induced by overexpressing or knocking down miR-24 or ING5. Hematoxylin and eosin
      (H&E) staining and immunohistochemical staining for ING5 and Ki-67 were used for
      xenograft assays in BALB/c nude mice. RESULTS: We showed that the ING5 protein
      rather than the mRNA, was significantly downregulated in breast cancer tissues.
      We also investigated the potential function of ING5 in breast tumorigenesis and
      found that ING5 suppressed the proliferation and invasion of breast cancer cells
      and promoted their apoptosis. Furthermore, we explored the molecular mechanisms
      accounting for the dysregulation of ING5 in breast cancer cells and identified an
      oncomiR, miR-24, as a direct upstream regulator of ING5. We revealed that miR-24
      had the opposite effects to those of ING5 on breast cancer cells and could
      accelerate xenografted tumor growth in vivo. CONCLUSION: Our findings uncover the
      tumor-suppressive role of ING5 and the regulatory pathway of ING5 in breast
      cancer and may provide insights into the molecular mechanisms of breast
      carcinogenesis.

PMID- 28490336
TI  - Characteristics of L-citrulline transport through blood-brain barrier in the
      brain capillary endothelial cell line (TR-BBB cells).
AB  - BACKGROUND: L-Citrulline is a neutral amino acid and a major precursor of L
      arginine in the nitric oxide (NO) cycle. Recently it has been reported that L
      citrulline prevents neuronal cell death and protects cerebrovascular injury,
      therefore, L-citrulline may have a neuroprotective effect to improve
      cerebrovascular dysfunction. Therefore, we aimed to clarify the brain transport
      mechanism of L-citrulline through blood-brain barrier (BBB) using the
      conditionally immortalized rat brain capillary endothelial cell line (TR-BBB
      cells), as an in vitro model of the BBB. METHODS: The uptake study of [14C] L
      citrulline, quantitative real-time polymerase chain reaction (PCR) analysis, and
      rLAT1, system b0,+, and CAT1 small interfering RNA study were performed in TR-BBB
      cells. RESULTS: The uptake of [14C] L-citrulline was a time-dependent, but ion
      independent manner in TR-BBB cells. The transport process involved two saturable
      components with a Michaelis-Menten constant of 30.9 +/- 1.0 MUM (Km1) and 1.69 +/
      0.43 mM (Km2). The uptake of [14C] L-citrulline in TR-BBB cells was
      significantly inhibited by neutral and cationic amino acids, but not by anionic
      amino acids. In addition, [14C]L-citrulline uptake in the cells was markedly
      inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), which is the
      inhibitor of the large neutral amino acid transporter 1 (LAT1), B0, B0,+ and
      harmaline, the inhibitor of system b0,+. Gabapentin and L-dopa as the substrates
      of LAT1 competitively inhibited the uptake of [14C] L-citrulline. IC50 values for
      L-dopa, gabapentin, L-phenylalanine and L-arginine were 501 MUM, 223 MUM, 68.9
      MUM and 33.4 mM, respectively. The expression of mRNA for LAT1 was predominantly
      increased 187-fold in comparison with that of system b0,+ in TR-BBB cells. In the
      studies of LAT1, system b0,+ and CAT1 knockdown via siRNA transfection into TR
      BBB cells, the transcript level of LAT1 and [14C] L-citrulline uptake by LAT1
      siRNA were significantly reduced compared with those by control siRNA in TR-BBB
      cells. CONCLUSIONS: Our results suggest that transport of L-citrulline is mainly
      mediated by LAT1 in TR-BBB cells. Delivery strategy for LAT1-mediated transport
      and supply of L-citrulline to the brain may serve as therapeutic approaches to
      improve its neuroprotective effect in patients with cerebrovascular disease.

PMID- 28490337
TI  - Effect of sitagliptin on the echocardiographic parameters of left ventricular
      diastolic function in patients with type 2 diabetes: a subgroup analysis of the
      PROLOGUE study.
AB  - BACKGROUND: Diabetes is associated closely with an increased risk of
      cardiovascular events, including diastolic dysfunction and heart failure that
      leads to a shortening of life expectancy. It is therefore extremely valuable to
      evaluate the impact of antidiabetic agents on cardiac function. However, the
      influence of dipeptidyl peptidase 4 inhibitors on cardiac function is
      controversial and a major matter of clinical concern. We therefore evaluated the
      effect of sitagliptin on echocardiographic parameters of diastolic function in
      patients with type 2 diabetes as a sub-analysis of the PROLOGUE study. METHODS:
      Patients in the PROLOGUE study were assigned randomly to either add-on
      sitagliptin treatment or conventional antidiabetic treatment. Of the 463 patients
      in the overall study, 115 patients (55 in the sitagliptin group and 60 in the
      conventional group) who had complete echocardiographic data of the ratio of peak
      early diastolic transmitral flow velocity (E) to peak early diastolic mitral
      annular velocity (e') at baseline and after 12 and 24 months were included in
      this study. The primary endpoint of this post hoc sub-analysis was a comparison
      of the changes in the ratio of E to e' (E/e') between the two groups from
      baseline to 24 months. RESULTS: The baseline-adjusted change in E/e' during 24
      months was significantly lower in the sitagliptin group than in the conventional
      group (-0.18 +/- 0.55 vs. 1.91 +/- 0.53, p = 0.008), irrespective of a higher
      E/e' value at baseline in the sitagliptin group. In analysis of covariance,
      sitagliptin treatment was significantly associated with change in E/e' over 24
      months (beta = -9.959, p = 0.001), independent of other clinical variables at
      baseline such as blood pressure, HbA1c, and medications for diabetes. Changes in
      other clinical variables including blood pressure and glycemic parameters, and
      echocardiographic parameters, such as cardiac structure and systolic function,
      were comparable between the two groups. There was also no significant difference
      in the serum levels of N-terminal-pro brain natriuretic peptide and high
      sensitive C-reactive protein between the two groups during the study period.
      CONCLUSIONS: Adding sitagliptin to conventional antidiabetic regimens in patients
      with T2DM for 24 months attenuated the annual exacerbation in the
      echocardiographic parameter of diastolic dysfunction (E/e') independent of other
      clinical variables such as blood pressure and glycemic control. Trial
      registration UMIN000004490 (University Hospital Medical Information Network
      Clinical Trials). https://upload.umin.ac.jp/cgi-open
      bin/ctr_e/ctr_view.cgi?recptno=R000005356 ; registered November 1, 2010.

PMID- 28490338
TI  - International evaluation of the psychometrics of health-related quality of life
      questionnaires for use among long-term survivors of testicular and prostate
      cancer.
AB  - BACKGROUND: Understanding of the physical, functional and psychosocial health
      problems and needs of cancer survivors requires cross-national and cross-cultural
      standardization of health-related quality of life (HRQoL) questionnaires that
      capture the full range of issues relevant to cancer survivors. To our knowledge,
      only one study has investigated in a comprehensive way whether a questionnaire
      used to evaluate HRQoL in cancer patients under active treatment is also reliable
      and valid when used among (long-term) cancer survivors. In this study we
      evaluated, in an international context, the psychometrics of HRQoL questionnaires
      for use among long-term, disease-free, survivors of testicular and prostate
      cancer. METHODS: In this cross-sectional study, we recruited long-term survivors
      of testicular and prostate cancer from Northern and Southern Europe and from the
      United Kingdom who had participated in two phase III EORTC clinical trials.
      Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire,
      the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer)
      questionnaires, and the Impact of Cancer questionnaire. Testicular cancer
      survivors also completed subscales from the Nordic Questionnaire for Monitoring
      the Age Diverse Workforce. RESULTS: Two hundred forty-two men (66% response rate)
      were recruited into the study. The average time since treatment was more than 10
      years. Overall, there were few missing questionnaire data, although scales
      related to sexuality, satisfaction with care and relationship concerns of men
      without partners were missing in more than 10% of cases. Debriefing showed that
      in general the questionnaires were accepted well. Many of the survivors scored at
      the upper extremes of the questionnaires, resulting in floor and ceiling effects
      in 64% of the scales. All of the questionnaires investigated met the threshold of
      0.70 for group level reliability, with the exception of the QLQ-TC26 (mean
      reliability .64) and the QLQ-PR25 (mean reliability .69). The questionnaires were
      able to discriminate clearly between patients with and without comorbid
      conditions. CONCLUSIONS: The currently available HRQoL questionnaires exhibit
      acceptable psychometric properties and were well received by patients, but
      additional efforts are needed to ensure that the full range of survivor-specific
      issues is assessed.

PMID- 28490339
TI  - Distribution and phylogeny of Wolbachia strains in wild mosquito populations in
      Sri Lanka.
AB  - BACKGROUND: Wolbachia are a group of maternally inherited intracellular bacteria
      known to be widespread among arthropods. Infections with Wolbachia cause declines
      of host populations, and also induce host resistance to a wide range of
      pathogens. Over the past few decades, researchers were curious to use Wolbachia
      as a biological tool to control mosquito vectors. During the present study,
      assessment of the prevalence of Wolbachia infections among wild mosquito
      populations in Sri Lanka where mosquito-borne diseases are a major health
      concern, was carried out for the first time. DNA was extracted from the abdomens
      of mosquitoes, collected from seven provinces, and screened for the presence of
      Wolbachia by PCR using wsp and groE primers. Group-specific and strain-specific
      primers were used to classify Wolbachia into the supergroups A and B, and into
      the strains Mel, AlbA and Pip. RESULTS: A total of 330 individual mosquitoes
      belonging to 22 species and 7 genera were screened. Eighty-seven mosquitoes
      (26.36%) belonging to four species (i.e. Aedes albopictus, Culex
      quinquefasciatus, Armigeres subalbatus and Mansonia uniformis) were positive for
      Wolbachia infections. Primary vector of the dengue fever, Ae. aegypti was
      negative for Wolbachia infections while the secondary vector, Ae. albopictus,
      showed a very high infection rate. The filarial vector C. quinquefasciatus had a
      relatively high rate of infection. Japanese encephalitis vectors C. gelidus and
      C. triteaneorynchus, and the Anopheles vectors of malaria were negative for
      Wolbachia infections. Nine sequences of Wolbachia-positive PCR products were
      deposited in the GenBank and compared with other available data. Aedes albopictus
      was infected with both Wolbachia strains A (AlbA) and B (Pip) supergroups.
      Phylogenetic analysis of the wsp sequences showed two major branches confirming
      identities obtained from the PCR screening with strain-specific primers.
      CONCLUSION: Wolbachia infections were found only among four mosquito species in
      Sri Lanka: Aedes albopictus, Culex quinquefasciatus, Armigeres subalbatus and
      Mansonia uniformis. Sequence data showed high haplotype diversity among the
      Wolbachia strains.

PMID- 28490340
TI  - Morbidity and oncologic outcome after saphenous vein-sparing inguinal
      lymphadenectomy in melanoma patients.
AB  - BACKGROUND: Inguinal lymph node dissection (LND) is a surgical procedure with a
      high morbidity rate. Variations in surgical procedure, such as sparing of the
      saphenous vein, have been proposed to reduce surgical morbidity. While sparing of
      the saphenous vein has shown promising results in earlier studies, data for this
      procedure in melanoma patients are rare. In this retrospective study, we report
      10-year findings on the effects of saphenous vein-sparing LND on surgical
      morbidity and oncologic outcomes in melanoma patients. METHODS: A retrospective
      analysis of melanoma patients receiving inguinal LND in our facility between 2003
      and 2013 was performed. Patients were divided into two groups: the saphenous vein
      resection group and the vein sparing group. Surgical morbidity, including wound
      infection, lymphatic fistula, severe bleeding, neurological complications, and
      chronic lymphedema, as well as regional recurrence-free survival were
      investigated. RESULTS: A total of 106 patients were included in this study; of
      these, the saphenous vein was spared in 41 patients (38.7%). The rate of
      lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%,
      and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena
      magna resection vs. sparing group. Differences observed, however, were not
      significant. No difference in regional recurrence-free survival between the two
      study groups was detected. CONCLUSIONS: The results of our retrospective analysis
      could not confirm the promising results reported in earlier studies. Thus,
      sparing of the saphenous vein appears to be optional.

PMID- 28490341
TI  - Developmental transitions: integrating environmental cues with hormonal signaling
      in the chromatin landscape in plants.
AB  - Plant development is predominantly postembryonic and tuned in to respond to
      environmental cues. All living plant cells can be triggered to de-differentiate,
      assume different cell identities, or form a new organism. This developmental
      plasticity is thought to be an adaptation to the sessile lifestyle of plants.
      Recent discoveries have advanced our understanding of the orchestration of plant
      developmental switches by transcriptional master regulators, chromatin state
      changes, and hormone response pathways. Here, we review these recent advances
      with emphasis on the earliest stages of plant development and on the switch from
      pluripotency to differentiation in different plant organ systems.

PMID- 28490343
TI  - Roadside opioid testing of drivers using oral fluid: the case of a country with a
      zero tolerance law, Spain.
AB  - BACKGROUND: Opioids can impair psychomotor performance, and driving under the
      influence of opioids is associated with an increased risk of accidents. The goals
      of this study were i) to determine the prevalence of opioids (heroin, morphine,
      codeine, methadone and tramadol) in Spanish drivers and ii) to explore the
      presence of opioids, more specifically whether they are used alone or in
      combination with other drugs. METHODS: The 2008/9 DRUID database regarding Spain
      was used, which provided information on 3302 drivers. All drivers included in the
      study provided a saliva sample and mass-chromatographic analyses were carried out
      in all cases. To determine the prevalence, the sample was weighted according to
      traffic intensity. In the case of opioid use combinations, the sample was not
      weighted. The detection limit for each substance was considered a positive
      result. RESULTS: The prevalence of opioids in Spanish drivers was 1.8% (95% CI,
      1.4-2.3). Polydrug detection was common (56.2%): of these, in two out of three
      cases, two opioids were detected and cocaine was also detected in 86% of the
      cases. The concentration (median [Q1-Q3] ng/ml) of the substances was low:
      methadone 1.71 [0.10-15.30], codeine 40.55 [2.10-120.77], 6-acetylmorphine 5.71
      [1.53-84.05], and morphine 37.40 [2.84-200.00]. Morphine was always detected with
      6-acetylmorphine (heroin use). CONCLUSIONS: Driving under the influence of
      opioids is relatively infrequent, but polydrug use is common. Our study shows
      that 6 out of 10 drivers with methadone in their OF (likely in methadone
      maintenance programs) are using other substances. This should be taken into
      account by health professionals in order to properly inform patients about the
      added risks of mixing substances when driving.

PMID- 28490342
TI  - Rethinking alcohol interventions in health care: a thematic meeting of the
      International Network on Brief Interventions for Alcohol & Other Drugs (INEBRIA).
AB  - In 2016, the International Network on Brief Interventions for Alcohol & Other
      Drugs convened a meeting titled "Rethinking alcohol interventions in health
      care". The aims of the meeting were to synthesize recent evidence about screening
      and brief intervention and to set directions for research, practice, and policy
      in light of this evidence. Screening and brief intervention is efficacious in
      reducing self-reported alcohol consumption for some with unhealthy alcohol use,
      but there are gaps in evidence for its effectiveness. Because screening and brief
      intervention is not known to be efficacious for individuals with more severe
      unhealthy alcohol use, recent data showing the lack of evidence for referral to
      treatment as part of screening and brief intervention are alarming. While
      screening and brief intervention was designed to be a population-based approach,
      its reach is limited. Implementation in real world care also remains a challenge.
      This report summarizes practice, research, and policy recommendations and key
      research developments from our meeting. In order to move the field forward, a
      research agenda was proposed to (1) address evidence gaps in screening, brief
      intervention, and referral to treatment, (2) develop innovations to address
      severe unhealthy alcohol use within primary care, (3) describe the stigma of
      unhealthy alcohol use, which obstructs progress in prevention and treatment, (4)
      reconsider existing conceptualizations of unhealthy alcohol use that may
      influence health care, and (5) identify efforts needed to improve the capacity
      for addressing unhealthy alcohol consumption in all world regions.

PMID- 28490344
TI  - Dosimetric advantage of volumetric modulated arc therapy in the treatment of
      intraocular cancer.
AB  - OBJECTIVE: The purpose of this study is to investigate the dosimetric advantages
      of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer
      by comparing it directly with three-dimensional conformal radiotherapy (CRT) and
      intensity-modulated radiotherapy (IMRT). METHODS: CRT plan, 7f-IMRT plan, and one
      arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and
      biological quality indices for target volume and organs at risks (OARs) were
      evaluated and compared. RESULTS: The target coverage presented by V95 for CRT,
      IMRT and VMAT were 95.02% +/- 0.67%, 95.51% +/- 2.25%, and 95.92% +/- 3.05%,
      respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 +/-
      0.05, 0.23 +/- 0.05, and 0.23 +/- 0.06, respectively. IMRT and VMAT greatly
      decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 +/-
      1407.12 cGy, 3317.82 +/- 915.28 cGy and 4809.54 +/- 524.60 cGy for IMRT, VMAT and
      CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT
      and VMAT also spared better on brainstem, optical nerves and optical chiasm
      compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT
      and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing.
      The average MUs and delivery time of IMRT and VMAT were 531.25 +/- 81.21 vs.
      400.99 +/- 61.49 and 5.05 +/- 0.53 vs.1.71 +/- 0.69 min, respectively.
      CONCLUSIONS: Although no clear distinction on PTV coverage among CRT, IMRT and
      VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT
      achieved better homogeneity and conformity for target volume, and delivered fewer
      doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT
      increased the low dose volume to the contralateral OARs. Although VMAT and IMRT
      showed mixed results on target coverage and OAR sparing, VMAT decreased MU and
      delivery time significantly compared with IMRT. VMAT is a promising and feasible
      external beam radiotherapy technique in the treatment of intraocular cancer
      patients.

PMID- 28490345
TI  - Post-2015, why delay to seek healthcare? Perceptions and field experiences from
      TB healthcare providers in northern Malawi: a qualitative study.
AB  - BACKGROUND: Malawi is a low-income country with high Tuberculosis (TB) burden. TB
      diagnosis delay and untimely initiation of treatment is still a major problem in
      Malawi which could increase the risk of tuberculosis transmission in the
      communities. This study investigated factors related to the diagnostic delay of
      tuberculosis from TB healthcare providers in the northern region of Malawi.
      METHODS: Nine focus group discussions were conducted with 57 participants in
      total. The participants were healthcare cadres including district TB officers,
      clinical officers, TB nurses, laboratory technicians and Health Surveillance
      Assistants (HSAs). NVivo (11.0) software was used for data analysis. RESULTS: The
      factors related to diagnostic delay were categorized into three themes: client
      factors, institutional factors and healthcare provider related factors. Client's
      stigma and fear for HIV test, resource shortage within healthcare institutions
      and the healthcare workers' poor attitude against potential patients were among
      the most influential factors behind the TB diagnostic delay. CONCLUSIONS: The TB
      control strategies should aim to reduce HIV stigma, improve resource supply and
      improve TB healthcare workers' morale in order to achieve timely TB diagnosis.

PMID- 28490347
TI  - GH-secreting pituitary macroadenoma (acromegaly) associated with progressive
      dental malocclusion and refractory CPAP treatment.
AB  - BACKGROUND: A link between progressive dental malocclusion, the use of a
      continuous positive airway pressure mask and GH-secreting pituitary macroadenoma
      (acromegaly) has not been previously reported. The present clinicopathological
      analysis stresses that tooth malposition should not be seen exclusively as a
      local process. CASE PRESENTATION: A 62-year-old caucasian man with no relevant
      medical history reported difficulty chewing food and perceived voice alteration
      during his annual periodontal check-up. He also referred stiffness of the tongue,
      face, and submandibular area. The patient had been diagnosed with obstructive
      sleep apnea syndrome two years previously, since when he had worn a continuous
      positive airway pressure device during sleep. Exploration of the occlusion
      revealed significant changes: an atypical left lateral and anterior open bite
      with major buccoversion of teeth 33, 34, 35, 36. Inspection of the soft tissue
      revealed only macroglossia, although external palpation indicated a subcutaneous
      stiffness of the submandibular area. General analytical tests, including hormone
      profiles, and magnetic resonance imaging confirmed the diagnosis of acromegaly
      induced by a pituitary adenoma. Intrasellar tumor resection via transsphenoidal
      approach was performed. After surgery, the patient already noted a marked
      improvement of all symptoms associated with the acromegaly. Desaturation data
      also evolved favourably and the pulmonologist advised the patient to abandon the
      continuous positive airway pressure treatment. CONCLUSION: Progressive dental
      malocclusion may be associated with a systemic disease and the use of a nasal
      mask with premaxillary support may distort the diagnosis of acromegaly.

PMID- 28490346
TI  - Anti-inflammatory effects of H2S during acute bacterial infection: a review.
AB  - Hydrogen sulfide (H2S), previously only considered a toxic environmental air
      pollutant, is now increasingly recognized as an important signaling molecule able
      to modulate several cellular pathways in many human tissues. As demonstrated in
      recent studies, H2S is produced endogenously in response to different cellular
      stimuli and plays different roles in controlling a number of physiological
      responses. The precise role of H2S in inflammation is still largely unknown. In
      particular, the role of H2S in the regulation of the inflammatory response in
      acute and chronic infections is being actively investigated because of its
      potential therapeutic use. To study the effect of H2S as an anti-inflammatory
      mediator during bacterial infections, we developed an ex vivo model of primary
      cells and cell lines infected with Mycoplasma. Our data demonstrate a dichotomic
      effect of H2S on the NF-kB and Nrf-2 molecular pathways, which were inhibited and
      stimulated, respectively.

PMID- 28490348
TI  - An international reproducibility study validating quantitative determination of
      ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper(r).
AB  - BACKGROUND: Accurate determination of the predictive markers human epidermal
      growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone
      receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for
      therapeutic decision making in early breast cancer. In this multicenter
      prospective study, we addressed the issue of inter- and intrasite reproducibility
      using the recently developed reverse transcription-quantitative real-time
      polymerase chain reaction-based MammaTyper(r) test. METHODS: Ten international
      pathology institutions participated in this study and determined messenger RNA
      expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally
      extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with
      the MammaTyper(r) test. Samples were measured repeatedly on different days within
      the local laboratories, and reproducibility was assessed by means of variance
      component analysis, Fleiss' kappa statistics, and interclass correlation
      coefficients (ICCs). RESULTS: Total variations in measurements of centrally and
      locally prepared RNA extracts were comparable; therefore, statistical analyses
      were performed on the complete dataset. Intersite reproducibility showed total
      SDs between 0.21 and 0.44 for the quantitative single-marker assessments,
      resulting in ICC values of 0.980-0.998, demonstrating excellent agreement of
      quantitative measurements. Also, the reproducibility of binary single-marker
      results (positive/negative), as well as the molecular subtype agreement, was
      almost perfect with kappa values ranging from 0.90 to 1.00. CONCLUSIONS: On the
      basis of these data, the MammaTyper(r) has the potential to substantially improve
      the current standards of breast cancer diagnostics by providing a highly precise
      and reproducible quantitative assessment of the established breast cancer
      biomarkers and molecular subtypes in a decentralized workup.

PMID- 28490350
TI  - Efficacy of the vegetative cells of Lysinibacillus sphaericus for biological
      control of insecticide-resistant Aedes aegypti.
AB  - BACKGROUND: The control of Aedes aegypti is usually based on chemical
      insecticides, but the overuse of these compounds has led to increased resistance.
      The binary toxin produced by Lysinibacillus sphaericus in the final stages of
      sporulation is used for mosquito control due to its specificity against the
      culicid larvae; however, it has been proved that Ae. aegypti is refractory for
      this toxin. Currently, there is no evidence of the use of L. sphaericus
      vegetative cells for mosquito biocontrol. Therefore, in this study, the
      vegetative cells of three L. sphaericus strains were assessed against a field
      collected Ae. aegypti, resistant to temephos, and the reference Rockefeller
      strain. RESULTS: Vegetative cells of L. sphaericus 2362, III(3)7 and OT4b.25
      produced between 90% and 100% of larvae mortality in the reference Rockefeller
      strain. Effective concentrations of each L. sphaericus strain for the four larval
      stages ranged from 1.4 to 2 * 107 CFU/ml. Likewise, a consortium of L. sphaericus
      assessed against a field-collected Ae. aegypti resistant to temephos and the
      Rockefeller strain caused 90% of larvae mortality. Concentrations of L.
      sphaericus consortium that resulted in larvae mortality of field-collected and
      Rockefeller Ae. aegypti ranged from 1.7 to 2.5 * 107 CFU/ml. The vegetative cells
      of L. sphaericus have no effect on the Ae. aegypti eggs and pupae. CONCLUSIONS:
      The vegetative cells of L. sphaericus are effective against Ae. aegypti larvae,
      meaning that it could be used in the biological control of these mosquito
      species. Since the L. sphaericus consortium was effective against temephos
      resistant Ae. aegypti, vegetative cells could be an alternative to overcome
      insecticide-resistant populations. Further studies, should be conducted to reveal
      the mode of action and the toxic principle of L. sphaericus vegetative cells.

PMID- 28490349
TI  - Cognitive behavioural therapy for the management of inflammatory bowel disease
      fatigue with a nested qualitative element: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Fatigue is one of the most prevalent and burdensome symptoms for
      patients with inflammatory bowel disease (IBD). Although fatigue increases during
      periods of inflammation, for some patients it persists when disease is in
      remission. Compared to other long-term conditions where fatigue has been
      extensively researched, optimal management of fatigue in patients with IBD is
      unknown and fatigue has rarely been the primary outcome in intervention studies.
      To date, interventions for the management of IBD-fatigue are sparse, have short
      term effects and have not been implemented within the existing health system.
      There is a need to integrate current best evidence across different conditions,
      patient experience and clinical expertise in order to develop interventions for
      IBD-fatigue management that are feasible and effective. Modifying an existing
      intervention for patients with multiple sclerosis, this study aims to assess the
      feasibility and initial estimates of efficacy of a cognitive behavioural therapy
      (CBT) intervention for the management of fatigue in patients with IBD. METHODS:
      The study will be a two-arm pilot randomised controlled trial. Patients will be
      recruited from one outpatient IBD clinic and randomised individually to either:
      Group 1 (CBT manual for the management of fatigue, one 60-min session and seven
      30-min telephone/Skype sessions with a therapist over an eight-week period); or
      Group 2 (fatigue information sheet to use without therapist help). Self-reported
      IBD-fatigue (Inflammatory Bowel Disease-Fatigue Scale) and IBD-quality of life
      (United Kingdom Inflammatory Bowel Disease Questionnaire) and self-reported
      disease activity will be collected at baseline, three, six and 12 months post
      randomisation. Illness perceptions, daytime sleepiness, anxiety and depression
      explanatory variables will be collected only at three months post randomisation.
      Clinical and sociodemographic data will be retrieved from the patients' medical
      notes. A nested qualitative study will evaluate patient and therapist experience,
      and healthcare professionals' perceptions of the intervention. DISCUSSION: The
      study will provide evidence of the feasibility and initial estimates of efficacy
      of a CBT intervention for the management of fatigue in patients with IBD.
      Quantitative and qualitative findings from the study will contribute to the
      development and implementation of a large-scale randomised controlled trial
      assessing the efficacy of CBT interventions for IBD-fatigue. TRIAL REGISTRATION:
      ISRCTN Registry, ISRCTN17917944 . Registered on 2 September 2016.

PMID- 28490351
TI  - Transcranial doppler sonography is not a valid diagnostic tool for detection of
      basilar artery stenosis or in-stent restenosis: a retrospective diagnostic study.
AB  - BACKGROUND: There are contradictory reports concerning the validity of
      transcranial sonography (TCD and TCCS) for examinations of the basilar artery.
      Here we investigated sensitivity and specificity of transcranial sonography for
      the detection of basilar artery stenosis and in-stent-restenosis compared to
      cerebral angiography. METHODS: We analyzed data of 104 examinations of the
      basilar artery. The association between sonographic peak systolic velocity (PSV)
      and degree of stenosis obtained by cerebral angiography was evaluated applying
      Spearman's correlation coefficient. Receiver Operating Characteristics (ROC)
      curves and areas under the curve (AUC) were calculated for the detection of a
      >=50% stenosis defined by angiography. Optimal cut-off was derived using the
      Youden-index. RESULTS: A weak but statistically significant correlation between
      PSV and the degree of stenosis was found (n=104, rho=0.35, p<0.001). ROC analysis
      for a detection of >=50% stenosis showed an AUC of 0.70, a sensitivity of 74.0%
      and a specificity of 65.0% at the optimal cut off of 124 cm/s. Results were
      consistent when analyzing examinations done in stented and unstented arteries
      separately (TCD VS DSA/CTA in unstented artery: AUC=0.66, sensitivity 61.0%,
      specificity 65.0%, TCD/TCCS VS DSA in stented artery: AUC=0.63, sensitivity
      71.0%, specificity 82.0%). Comparing TCCS measurements exclusively to
      angiography, ROC analysis showed an AUC of 1.00 for the detection of an in-stent
      restenosis >=50% with a sensitivity and specificity of 100% when a PSV of 132
      cm/s was used as a cut off value. CONCLUSION: Validity of TCD in the assessment
      of basilar artery stenosis or in-stent restenosis is poor. First results for TCCS
      are promising, but due to the small samplesize further studies with larger
      samples sizes are warranted.

PMID- 28490352
TI  - A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR
      metabolomics study of selected patients and controls.
AB  - BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible
      pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers
      for objective identification of affected individuals is a continuing endeavour in
      FMS research. Our objective was to perform an explorative metabolomics study (1)
      to elucidate the global urinary metabolite profile of patients suffering from
      FMS, and (2) to explore the potential of this metabolite information to augment
      existing medical practice in diagnosing the disease. METHODS: We selected
      patients with a medical history of persistent FMS (n = 18), who described their
      recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR)
      and an in-house clinical questionnaire (IHCQ). Three control groups were used:
      first-generation family members of the patients (n = 11), age-related individuals
      without any indications of FMS or related conditions (n = 10), and healthy young
      (18-22 years) individuals (n = 20). All subjects were female and the biofluid
      under investigation was urine. Correlation analysis of the FIQR showed the FMS
      patients represented a well-defined disease group for this metabolomics study.
      Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic
      resonance (NMR) spectrometer; data processing and analyses were performed using
      Matlab, R, SPSS and SAS software. RESULTS AND DISCUSSION: Unsupervised and
      supervised multivariate analyses distinguished all three control groups and the
      FMS patients, and significant increases in metabolites related to the gut
      microbiome (hippuric, succinic and lactic acids) were observed. We have developed
      an algorithm for the diagnosis of FMS consisting of three metabolites - succinic
      acid, taurine and creatine - that have a good level of diagnostic accuracy
      (Receiver Operating Characteristic (ROC) analysis - area under the curve 90%) and
      on the pain and fatigue symptoms for the selected FMS patient group. CONCLUSION:
      Our data and comparative analyses indicated an altered metabolic profile of
      patients with FMS, analytically detectable within their urine. Validation studies
      may substantiate urinary metabolites to supplement information from medical
      assessment, tender-point measurements and FIQR questionnaires for an improved
      objective diagnosis of FMS.

PMID- 28490353
TI  - Implementation of depression screening in antenatal clinics through tablet
      computers: results of a feasibility study.
AB  - BACKGROUND: Mobile devices may facilitate depression screening in the waiting
      area of antenatal clinics. This can present implementation challenges, of which
      we focused on survey layout and technology deployment. METHODS: We assessed the
      feasibility of using tablet computers to administer a socio-demographic survey,
      the Whooley questions and the Edinburgh Postnatal Depression Scale (EPDS) to 530
      pregnant women attending National Health Service (NHS) antenatal clinics across
      England. We randomised participants to one of two layout versions of these
      surveys: (i) a scrolling layout where each survey was presented on a single
      screen; or (ii) a paging layout where only one question appeared on the screen at
      any given time. RESULTS: Overall, 85.10% of eligible pregnant women agreed to
      take part. Of these, 90.95% completed the study procedures. Approximately 23% of
      participants answered Yes to at least one Whooley question, and approximately 13%
      of them scored 10 points of more on the EPDS. We observed no association between
      survey layout and the responses given to the Whooley questions, the median EPDS
      scores, the number of participants at increased risk of self-harm, and the number
      of participants asking for technical assistance. However, we observed a
      difference in the number of participants at each EPDS scoring interval (p =
      0.008), which provide an indication of a woman's risk of depression. A scrolling
      layout resulted in faster completion times (median = 4 min 46 s) than a paging
      layout (median = 5 min 33 s) (p = 0.024). However, the clinical significance of
      this difference (47.5 s) is yet to be determined. CONCLUSIONS: Tablet computers
      can be used for depression screening in the waiting area of antenatal clinics.
      This requires the careful consideration of clinical workflows, and technology
      related issues such as connectivity and security. An association between survey
      layout and EPDS scoring intervals needs to be explored further to determine if it
      corresponds to a survey layout effect. Future research needs to evaluate the
      effect of this type of antenatal depression screening on clinical outcomes and
      clinic workflows. TRIAL REGISTRATION: This study was registered in
      ClinicalTrials.gov under the identifier NCT02516982 on 20 July 2015.

PMID- 28490354
TI  - Dual-time-point myocardial 18F-FDG imaging in the detection of coronary artery
      disease.
AB  - BACKGROUND: Myocardial 18F-deoxyglucose (18F-FDG) uptake has been observed to be
      enhanced in patients with coronary artery disease (CAD) under fasting conditions.
      However, whether the increased 18F-FDG is induced by myocardial ischemia and how
      to discriminate ischemic from physiological 18F-FDG uptake have rarely been
      investigated. METHODS: Under fasting conditions, 18F-FDG PET imaging was
      performed in 52 patients with suspected CAD. Two 18F-FDG imaging sessions were
      conducted within two hours after a single administration of 18F-FDG (dual-time
      point imaging), and with an intervention of an exercise test after the first
      imaging. Abnormal 18F-FDG uptake was determined by the classification of the 18F
      FDG distribution pattern, and the changes of the 18F-FDG distribution between the
      two PET imaging sessions were analyzed. 99mTc-sestamibi was injected at peak
      exercise and myocardial perfusion imaging (MPI) was conducted after 18F-FDG
      imaging. Coronary angiography was considered the reference for diagnosing CAD.
      RESULTS: Overall, 54.8% (17/31) of CAD patients and 36.2% (21/58) of stenotic
      coronaries showed exercise-induced abnormal uptake of 18F-FDG. Based on the
      classification of the 18F-FDG distribution pattern, the sensitivity and
      specificity of exercise 18F-FDG imaging to diagnose CAD was 80.6% and 95.2% by
      patient analysis, 56.9% and 98.0% by vascular analysis, respectively. Compared
      with MPI, 18F-FDG imaging had a tendency to have higher sensitivity (80.6% vs
      64.5%, P = 0.06) on the patient level. CONCLUSION: Myocardial ischemia can induce
      18F-FDG uptake. With the classification of the 18F-FDG distribution pattern, dual
      time-point 18F-FDG imaging under fasting conditions is efficient in diagnosing
      CAD.

PMID- 28490355
TI  - Regional inequity in complete antenatal services and public emergency obstetric
      care is associated with greater burden of maternal deaths: analysis from
      consecutive district level facility survey of Karnataka, India.
AB  - BACKGROUND: This equity focused evaluation analyses change in inter-district
      inequity of maternal health services (MHS) in Karnataka state between 2006-07 &
      2012-13, alongside association of MHS inequity with distribution of maternal
      deaths. METHODS: Repeated cross-sectional analysis of inequity and decomposition
      was done on nine district level MHS indicators using Theil's T index. Data was
      obtained from population linked district level facility surveys and health
      information systems. RESULTS: Inequity in births attended by skill birth
      attendants decreased the most (83.16%) among six other MHS indicators. Community
      provision of comprehensive emergency obstetric care strategy remained stagnant.
      Districts with higher complete antenatal care share and C-sections in public
      settings had lesser share of state's maternal deaths (R2 = 0.29, p = 0.004). 5
      districts suffered perpetual inequity of MHS with relatively greater burden of
      maternal deaths. CONCLUSION: First 6 years of national rural health mission
      increased coverage of MHS and decreased regional inequity albeit non-uniformly.
      Distribution of system driven interventions of complete ANC and C-sections appear
      to determine decrease of maternal mortality in Karnataka.

PMID- 28490357
TI  - Erratum to: Impact of medication adherence on renal function in comorbid patients
      with type 2 diabetes and depression: protocol for a cohort study.

PMID- 28490356
TI  - Transhepatic arterial infusion chemotherapy using a combination of miriplatin and
      CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma:
      a randomized controlled trial.
AB  - BACKGROUND: Based on promising results from a Phase I study of hepatic arterial
      infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP
      H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter,
      open-label, randomized phase II study was conducted to evaluate the efficacy and
      safety of the combination therapy versus miriplatin monotherapy. METHODS:
      Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging
      classification A and B cases, respectively, were randomly assigned to receive
      either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n
      = 10). DDP-H and/or miriplatin were administered through the hepatic arteries
      supplying the lobes of the liver containing tumors, and progression free survival
      was analyzed as a primary end point in addition to other secondary endpoints. The
      corresponding therapy was repeated unless disease progression or severe adverse
      events were recorded. RESULTS: The monotherapy or combination therapy was
      performed for 15 or 36 sessions in total, respectively. Although there were no
      significant differences between the two groups for treatment intervals (p = 0.96)
      or the dose of miriplatin used in each session (p = 0.99), the progression free
      survival and overall disease control rate were significantly better in the
      combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025,
      respectively). Consistent with these observations, a trend of a significantly
      slower increase in des-gamma-carboxyprothrombin was observed, and the number of
      treatment sessions was nearly significantly larger in the combination therapy
      group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time
      did not show a significant difference (706 days, monotherapy vs 733 days,
      combination therapy; p = 0.40). A significant decrease in cholinesterase was
      observed during the course of treatment only in patients receiving combination
      therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological
      and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).
      CONCLUSIONS: The higher disease control effects with the combination of
      miriplatin and DDP-H indicate that it is a promising alternative treatment for
      cases with multiple HCCs, especially for those that can tolerate the treatment
      without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION: This
      study was registered on 1 January 2012 with the University Hospital Medical
      Information Network Clinical Trials Registry (
      http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).

PMID- 28490358
TI  - Effectively engaging stakeholders and the public in developing violence
      prevention messages.
AB  - BACKGROUND: Preventing family violence requires that stakeholders and the broader
      public be involved in developing evidence-based violence prevention strategies.
      However, gaps exist in between what we know (knowledge), what we do (action), and
      the structures supporting practice (policy). DISCUSSION: We discuss the broad
      challenge of mobilizing knowledge-for-action in family violence, with a primary
      focus on the issue of how stakeholders and the public can be effectively engaged
      when developing and communicating evidence-based violence prevention messages. We
      suggest that a comprehensive approach to stakeholder and public engagement in
      developing violence prevention messages includes: 1) clear and consistent
      messaging; 2) identifying and using, as appropriate, lessons from campaigns that
      show evidence of reducing specific types of violence; and 3) evidence-informed
      approaches for communicating to specific groups. Components of a comprehensive
      approach must take into account the available research evidence, implementation
      feasibility, and the context-specific nature of family violence. While strategies
      exist for engaging stakeholders and the public in messaging about family violence
      prevention, knowledge mobilization must be informed by evidence, dialogue with
      stakeholders, and proactive media strategies. This paper will be of interest to
      public health practitioners or others involved in planning and implementing
      violence prevention programs because it highlights what is known about the issue,
      potential solutions, and implementation considerations.

PMID- 28490359
TI  - Cryopreservation of reproductive material before cancer treatment: a qualitative
      study of health care professionals' views about ways to enhance clinical care.
AB  - BACKGROUND: Cancer treatment can diminish fertility in women and men. The need
      for fertility preservation is growing as increasing numbers of people survive
      cancer. Cryostorage of reproductive material to preserve potential for conception
      for cancer survivors has moved from being experimental to being a part of
      clinical management of women and men who are diagnosed with cancer in their
      reproductive years. There is little existing evidence about how fertility
      preservation services can be enhanced to meet the complex needs of patients who
      are diagnosed with cancer in their reproductive years. The aim of this research
      was to inform clinical practice development by drawing on the collective
      experience and knowledge of staff at well-established clinics that offer
      fertility preservation before cancer treatment. METHODS: A qualitative research
      model was adopted using semi-structured interviews with professionals involved in
      the care of people who freeze reproductive material before cancer treatment. In
      the state of Victoria, Australia, two large assisted reproductive technology
      (ART) centres have been providing fertility preservation services for more than
      two decades. An invitation to participate in a semi-structured interview about
      clinical care in the context of fertility preservation was emailed to past and
      current staff members. To capture diverse perspectives, informants were sought
      from all relevant professions: fertility specialists, andrologists, nurses,
      embryologists/scientists, counsellors, and administrative staff. Transcripts were
      analysed thematically. RESULTS: Thirteen key informants were interviewed from
      August 2013 to February 2014. The identified themes relating to enhancing
      clinical care in a fertility preservation service were communication between
      oncology and ART specialists; managing urgency; managing patients' expectations;
      establishing and implementing protocols, systems, and data bases; and maintaining
      contact with patients. CONCLUSION: The collective knowledge of this study's
      informants, who represent multidisciplinary teams with more than two decades'
      experience in fertility preservation, yields important insights into strategies
      that fertility preservation services can employ to promote the integration of
      oncology and fertility care, the psychosocial care of patients, data recording
      and monitoring, and reporting of outcomes.

PMID- 28490360
TI  - Stability and relative validity of the Neuromuscular Disease Impact Profile
      (NMDIP).
AB  - BACKGROUND: The aim of this study was to examine the stability and relative
      validity (RV) of the Neuromuscular Disease Impact Profile (NMDIP) using criterion
      related groups. In a previous study the NMDIP-scales showed good internal
      consistency, convergent and discriminant validity. Known-groups analysis showed
      that the NMDIP discriminates between categories of extent of limitations.
      METHODS: A cross-sectional postal survey study was performed on patients
      diagnosed with a NMD and registered at the Department of Neurology, University
      Medical Center Groningen, the Netherlands. Participants were asked to complete
      the preliminary NMDIP, the Medical Outcome study Short Form Questionnaire (SF
      36), the World Health Organization Quality Of Life-abbreviation version (WHOQOL
      bref), and two generic domain specific measures: the Groningen Activity
      Restriction Scale (GARS) and the Impact on Participation and Autonomy
      Questionnaire (IPAQ). The variables 'Extent of Limitations' and 'Quality of Life'
      were used to create criterion-related groups. Stability over time was tested
      using the Wilcoxon Signed Rank Test for paired samples and the intraclass
      correlation coefficients for repeated measures. RV was examined by comparing the
      ability of NMDIP with generic multidimensional health impact measures, and domain
      specific measures in discriminating between criterion-related subgroups using the
      Kruskal-Wallis H-test. RESULTS: Response rate was 70% (n = 702). The NMDIP-scales
      showed sufficient stability over time, and satisfactory or strong RV. In general,
      the NMDIP scales performed as well as or better than the concurrent measurement
      instruments. CONCLUSIONS: The NMDIP proved to be a valid and reliable disease
      targeted measure with a broad scope on physical, psychological and social
      functioning.

PMID- 28490361
TI  - Adducin family proteins possess different nuclear export potentials.
AB  - BACKGROUND: The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are
      actin-binding proteins that play important roles in the stabilization of membrane
      cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly
      conserved bipartite nuclear localization signal (NLS) at the carboxyl termini,
      but only ADD1 can localize to the nucleus. The reason for this discrepancy is not
      clear. METHODS: To avoid the potential effect of cell-cell junctions on the
      distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were
      transiently expressed in NIH3T3 fibroblasts and their distribution in the
      cytoplasm and nucleus was examined by immunofluorescence staining. Several
      nuclear proteins were identified to interact with ADD1 by mass spectrometry,
      which were further verified by co-immunoprecipitation. RESULTS: In this study, we
      found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2
      and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were
      partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1
      inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the
      cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and
      are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we
      found that ADD2 and ADD3 possess much higher potential to counteract the activity
      of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD
      proteins appear to contain multiple nuclear export signals mainly in their head
      and neck domains. However, except for the leucine-rich motif
      (377FEALMRMLDWLGYRT391) in the neck domain of ADD1, no other classic nuclear
      export signal was identified in the ADD proteins. In addition, the nuclear
      retention of ADD1 facilitates its interaction with RNA polymerase II and zinc
      finger protein 331. CONCLUSIONS: Our results suggest that ADD2 and ADD3 possess
      functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in
      the subcellular localization of the ADD isoforms arises due to their different
      nuclear export capabilities. In addition, the interaction of ADD1 with RNA
      polymerase II and zinc-finger protein 331 implicates a potential role for ADD1 in
      the regulation of transcription.

PMID- 28490362
TI  - Different perceptions of narrative medicine between Western and Chinese medicine
      students.
AB  - BACKGROUND: Western medicine is an evidence-based science, whereas Chinese
      medicine is more of a healing art. To date, there has been no research that has
      examined whether students of Western and Chinese medicine differentially engage
      in, or benefit from, educational activities for narrative medicine. This study
      fills a gap in current literature with the aim of evaluating and comparing
      Western and Chinese Medicine students' perceptions of narrative medicine as an
      approach to learning empathy and professionalism. METHODS: An initial 10-item
      questionnaire with a 5-point Likert scale was developed to assess fifth-year
      Western medical (MS) and traditional Chinese medical (TCMS) students' perceptions
      of a 4-activity narrative medicine program during a 13-week internal medicine
      clerkship. Exploratory factor analysis was undertaken. RESULTS: The response rate
      was 88.6% (412/465), including 270 (65.5%) MSs and 142 (34.5%) TCMSs, with a
      large reliability (Cronbach alpha = 0.934). Three factors were extracted from 9
      items: personal attitude, self-development/reflection, and emotional benefit,
      more favorable in terms of enhancement of self-development/reflection. The
      perceptions of narrative medicine by scores between the two groups were
      significantly higher in TCMSs than MSs in all 9-item questionnaire and 3
      extracted factors. CONCLUSIONS: Given the different learning cultures of medical
      education in which these student groups engage, this suggests that undertaking a
      course in Chinese medicine might enhance one's acceptance to, and benefit from, a
      medical humanities course. Alternatively, Chinese medicine programmes might
      attract more humanities-focused students.

PMID- 28490363
TI  - Erratum to: Imported arboviral infections in Italy, July 2014-October 2015: a
      National Reference Laboratory report.

PMID- 28490366
TI  - Erratum to: Malaria parasite clearance.

PMID- 28490365
TI  - Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by
      miRNA-1-2 via WNT signaling pathway.
AB  - BACKGROUND: Bone marrow derived stem cells (BMSCs) have the potential to
      differentiate into cardiomyocytes, but the rate of differentiation is low and the
      mechanism of differentiation is unclear completely. Here, we aimed to investigate
      the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like
      cells and reveal the involved signaling pathways in the procedure. METHODS: Mouse
      BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac
      cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR. The
      apoptosis rate was detected by flow cytometry and the activity of the Wnt/beta
      catenin signaling pathway was evaluated by measuring the upstream protein of this
      signaling pathway. RESULTS: After over-expression of miR1-2 in mouse BMSCs, the
      apoptosis rate was significantly lower than the 5-aza group, while the
      expressions of cardiac-specific genes: such as Nkx2.5, cTnI and GATA4 were
      significantly increased compared to the control group and the 5-aza group.
      Meanwhile, over-expression of miR1-2 in mouse BMSCs enhanced the expression of
      wnt11, JNK, beta-catenin and TCF in the Wnt/beta-catenin signaling pathway. Use
      of LGK-974, an inhibitor of Wnt/beta-catenin signaling pathway, significantly
      reduced the expression of cardiac-specific genes and partially blocked the role
      of the miR1-2. CONCLUSION: Over-expression of miR1-2 in mouse BMSCs can induce
      them toward promoted cardiomyocyte differentiation via the activation of the
      Wnt/beta-catenin signaling pathway. Compared to 5-aza, miR1-2 can induce
      differentiation of BMSCs into cardiomyocytes more effectively with a less
      cytotoxicity.

PMID- 28490364
TI  - Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and
      review of 76 cases.
AB  - BACKGROUND: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset
      muscle disorder, characterized by the presence of nemaline rods in muscle fibers.
      Phenotypic characterization in a large cohort and a comprehensive overview of
      SLONM are lacking. METHODS: We studied the clinico-pathological features,
      treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10
      new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966
      2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV
      NM) cases. In 6 SLONM patients, we performed a targeted next-generation
      sequencing (NGS) panel comprising 283 myopathy genes. RESULTS: SLONM patients had
      a mean age at onset of 52 years. The predominant phenotype consisted of weakness
      and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and
      both in 67%. Other common symptoms included axial weakness in 68%, as well as
      dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal
      gammopathy of unknown significance (MGUS) was detected in serum. The mean
      percentage of muscle fibers containing rods was 28% (range 1-63%). In 2 cases
      ultrastructural analysis was necessary to detect the rods. The most successful
      treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem
      cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did
      not reveal causative pathogenic variants. In a comparison of SLONM patients with
      and without MGUS, the former comprised significantly more males, had more rapid
      disease progression, and more vacuolar changes in muscle fibers. Interestingly,
      the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods,
      whereas this feature was not seen in any of the biopsies from patients without
      paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM
      patients were male, with a lower age at onset (mean 34 years). In addition,
      immunosuppression was more frequently applied with more favorable outcome, and
      muscle biopsies revealed a significantly higher degree of inflammation and
      necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM
      patients. CONCLUSIONS: SLONM presents a challenging, but important differential
      diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS
      and HIV should be performed, as they require distinct but often effective
      therapeutic approaches. Even though SLONM and HIV-NM show some differences, there
      exists a large clinico-pathological overlap between the 2 entities.

PMID- 28490368
TI  - Erratum to: Genomic characterization of plant cell wall degrading enzymes and in
      silico analysis of xylanases and polygalacturonases of Fusarium virguliforme.

PMID- 28490367
TI  - Vitamin D deficiency among smear positive pulmonary tuberculosis patients and
      their tuberculosis negative household contacts in Northwest Ethiopia: a case
      control study.
AB  - BACKGROUND: Vitamin D is a fat-soluble vitamin that increases the immunity
      against tuberculosis (TB), decreases the re-activation of latent TB and reduces
      the severity of active TB disease. Epidemiological studies on the prevalence of
      vitamin D deficiency, and its association with TB showed inconsistent results in
      different countries. This study was aimed to determine the prevalence of vitamin
      D deficiency and its association with TB in Northwest Ethiopia. METHODS: A case
      control study was conducted among smear positive pulmonary tuberculosis patients
      and their household contacts without symptoms suggestive of TB. Study
      participants were recruited at 11 TB diagnostic health facilities in North and
      South Gondar zones of Amhara region between May 2013 and April 2015. The spot
      morning-spot sputum samples and 5 ml blood sample were collected prior to
      commencing TB treatment for the diagnosis of TB and serum vitamin D assay,
      respectively. The diagnosis of TB was performed using smear microscopy and
      GeneXpert. Serum vitamin D level was analyzed using VIDAS 25 OH Vitamin D Total
      testing kits (Biomerieux, Marcy I'Etoile, France) on mini VIDAS automated
      immunoassay platform. Vitamin D status was interpreted as deficient (<20 ng/ml),
      insufficient (20-29 ng/ml), sufficient (30-100 ng/ml) and potential toxicity
      (>100 ng/ml). RESULTS: Of the total study participants, 134 (46.2%) were vitamin
      D deficient, and only 56 (19.3%) had sufficient vitamin D level. A total of 59
      (61.5%) TB patients and 75 (38.7%) non TB controls were vitamin D deficient.
      Results of multivariate logistic regression analyses showed a significantly
      higher vitamin D deficiency among tuberculosis cases (p < 0.001), females (p =
      0.002), and urban residents (p < 0.001) than their respective comparison groups.
      Moreover, age groups of 35-44 (p = 0.001), 45-54 (p = 0.003) and >=55 (p = 0.001)
      years had significantly higher vitamin D deficiency compared with age group <15
      years. CONCLUSIONS: Vitamin D deficiency is highly prevalent among TB patients
      and non TB controls in Ethiopia where there is year round abundant sunshine.
      Study participants with tuberculosis, females, older age groups, and urban
      residents had significantly higher prevalence of vitamin D deficiency. These
      findings warrant further studies to investigate the role of vitamin D
      supplementation in the prevention and treatment of tuberculosis in high TB burden
      countries like Ethiopia.

PMID- 28490369
TI  - Erratum to: Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic
      cardiomyopathy with early repolarization and short QT syndrome.

PMID- 28490370
TI  - Behavioral interventions to promote adequate sleep among women: protocol for a
      systematic review and meta-analysis.
AB  - BACKGROUND: Short and poor sleep have been associated with adverse health
      outcomes in adults, such as overweight/obesity and type 2 diabetes, especially
      among women. Women therefore represent an important target for interventions
      aimed at improving sleep and such interventions have been advocated to enhance
      maternal, fetal, and infant health. This systematic review will assess the
      efficacy or effectiveness of behavioral interventions aimed at promoting adequate
      sleep among women. The primary outcomes will be changes in sleep duration and/or
      sleep quality from baseline to post-intervention and to the last available follow
      up measured either through self-reports or objectively. Secondary outcomes will
      be assessing the behavior change techniques that are responsible for the changes
      in sleep duration and quality among women. METHODS: Behavioral interventions that
      are non-pharmacological and target either sleep directly or sleep hygiene
      behaviors will be included. Randomized controlled trials, quasi-experimental, and
      one-group pre-post studies will be included, but treated separately in the
      analyses, given that a limited number of studies on the topic of sleep is
      expected. MEDLINE/PubMed, PsycINFO, CINAHL, EMBASE, and Proquest Dissertations
      and Theses will be investigated. There will be no restriction on the year of
      publication of the articles, but we will include only the ones written in English
      or French. Two authors will independently assess articles for eligibility and
      will extract data using a standardized data extraction form that will have been
      previously pilot-tested. The quality of the studies will be assessed using the
      Effective Public Health Practice Project tool for quantitative study designs. The
      intervention procedures will be classified according to the latest validated
      taxonomy of behavior change techniques. If there is a sufficient number of
      studies (k > 5), a meta-analysis of the results will be performed with a random
      effect model. If the heterogeneity is high (I 2 >= 75%), it will be investigated
      through sensitivity analyses and meta-regression. DISCUSSION: This review will
      provide valuable information to those interested in promoting adequate sleep
      among women and, hopefully, encourage additional research in this important field
      to promote maternal, fetal, and infant health. SYSTEMATIC REVIEW REGISTRATION:
      The study protocol was registered in PROSPERO in October 2016 (CRD42016049538).

PMID- 28490371
TI  - Purification and properties of a novel quizalofop-p-ethyl-hydrolyzing esterase
      involved in quizalofop-p-ethyl degradation by Pseudomonas sp. J-2.
AB  - Quizalofop-p-ethyl (QPE) is a post-emergence herbicide that effectively controls
      grass weeds and is often detected in the environment. However, the biochemical
      and molecular mechanisms of QPE degradation in the environment remains unclear.
      In this study, a highly effective QPE-degrading bacterial strain J-2 was isolated
      from acclimated activated sludge and identified as a Pseudomonas sp., containing
      the QPE breakdown metabolite quizalofop acid (QA) identified by Liquid
      Chromatography-Ion Trap-Mass Spectrometry (LC-IT-MSn) analysis. A novel QPE
      hydrolase esterase-encoding gene qpeH was cloned from strain J-2 and functionally
      expressed in Escherichia coli BL21 (DE3). The specific activity of recombinant
      QpeH was 198.9 +/- 2.7 U mg-1 for QPE with K m and K cat values of 41.3 +/- 3.6
      MUM and 127.3 +/- 4.5 s-1. The optimal pH and temperature for the recombinant
      QpeH were 8.0 and 30  degrees C, respectively and the enzyme was activated by
      Ca2+, Cd2+, Li+, Fe3+ and Co2+ and inhibited by Ni2+, Fe2+, Ag+, DEPC, SDS, Tween
      80, Triton X, beta-mercaptoethanol, PMSF, and pCMB. In addition, the catalytic
      efficiency of QpeH toward different AOPP herbicides in descending order was as
      follows: fenoxaprop-P-ethyl > quizalofop-P-tefuryl > QPE > haloxyfop-P-methyl >
      cyhalofopbutyl > clodinafop-propargyl. On the basis of the phylogenetic analysis
      and multiple sequence alignment, the identified enzyme QpeH, was clustered with
      esterase family V, suggesting a new member of this family because of its low
      similarity of amino acid sequence with esterases reported previously.

PMID- 28490372
TI  - Erratum to: Does a quality improvement campaign accelerate take-up of new
      evidence? A ten-state cluster-randomized controlled trial of the IHI's Project
      JOINTS.

PMID- 28490373
TI  - Thioredoxin-interacting protein links endoplasmic reticulum stress to
      inflammatory brain injury and apoptosis after subarachnoid haemorrhage.
AB  - BACKGROUND: Early brain injury (EBI) is considered a major contributor to the
      high morbidity and mortality associated with subarachnoid haemorrhage (SAH). Both
      of sterile inflammation and apoptosis are considered the important causes of EBI.
      Recently, it was confirmed that thioredoxin-interacting protein (TXNIP) not only
      participates in inflammatory amplification but also stimulates the apoptosis
      signalling cascade pathway. However, whether the effects of TXNIP influence the
      pathogenesis of SAH remains unclear. Here, we hypothesize that TXNIP activity
      induced by endoplasmic reticulum stress (ER stress) may contribute to the
      pathogenesis of EBI through pro-inflammatory and pro-apoptotic mechanisms.
      METHODS: A total of 299 male Sprague-Dawley rats were used to create SAH models.
      Resveratrol (RES, 60 mg/kg) and two TXNIP small interfering RNA (siRNA) were used
      to inhibit TXNIP expression. The specific inhibitors of ER stress sensors were
      used to disrupt the link between TXNIP and ER stress. SAH grade, neurological
      deficits, brain water content and blood-brain barrier (BBB) permeability were
      evaluated simultaneously as prognostic indicators. Fluorescent double-labelling
      was employed to detect the location of TXNIP in cerebral cells. Western blot and
      TUNEL were performed to study the mechanisms of TXNIP and EBI. RESULTS: We found
      that TXNIP expression significantly increased after SAH, peaking at 48 h (0.48 +/
      0.04, up to 3.2-fold) and decreasing at 72 h after surgery. This process was
      accompanied by the generation of inflammation-associated factors. TXNIP was
      expressed in the cytoplasm of neurons and was widely co-localized with TUNEL
      positive cells in both the hippocampus and the cortex of SAH rats. We discovered
      for the first time that TXNIP was co-localized in neural immunocytes (microglia
      and astrocytes). After administration of RES, TXNIP siRNA and ER stress
      inhibitors, TXNIP expression was significantly reduced and the crosstalk between
      TXNIP and ER stress was disrupted; this was accompanied by a reduction in
      inflammatory and apoptotic factors, as well as attenuation of the prognostic
      indices. CONCLUSIONS: These results may represent the critical evidence to
      support the pro-inflammatory and pro-apoptotic effects of TXNIP after SAH. Our
      data suggest that TXNIP participates in EBI after SAH by mediating inflammation
      and apoptosis; these pathways may represent a potential therapeutic strategy for
      SAH treatment.

PMID- 28490374
TI  - A serosurvey of selected cystogenic coccidia in Spanish equids: first detection
      of anti-Besnoitia spp. specific antibodies in Europe.
AB  - BACKGROUND: Equine besnoitiosis, caused by Besnoitia bennetti, and equine
      protozoal myeloencephalitis (EPM), caused by Sarcocystis neurona and Neospora
      hughesi are relevant equine diseases in the Americas that have been scarcely
      studied in Europe. Thus, a serosurvey of these cystogenic coccidia was carried
      out in Southern Spain. A cross-sectional study was performed and serum samples
      from horses (n = 553), donkeys (n = 85) and mules (n = 83) were included. An in
      house enzyme-linked immunosorbent assay (ELISA) was employed to identify a
      Besnoitia spp. infection and positive results were confirmed by an a posteriori
      western blot. For Neospora spp. and Sarcocystis spp., infections were detected
      using in-house ELISAs based on the parasite surface antigens N. hughesi rNhSAG1
      and S. neurona rSnSAG2/3/4. Risk factors associated with these protozoan
      infections were also investigated. RESULTS: Antibodies against Besnoitia spp.,
      Neospora spp. and Sarcocystis spp. infections were detected in 51 (7.1%), 46
      (6.4%) and 20 (2.8%) of 721 equids, respectively. The principal risk factors
      associated with a higher seroprevalence of Besnoitia spp. were the host species
      (mule or donkey), the absence of shelter and the absence of a rodent control
      programme. The presence of rodents was the only risk factor for Neospora spp.
      infection. CONCLUSIONS: This study was the first extensive serosurvey of
      Besnoitia spp. infection in European equids accomplished by two complementary
      tests and gives evidence of the presence of specific antibodies in these
      populations. However, the origin of the infection is still unclear. Further
      parasite detection and molecular genotyping are needed to identify the causative
      Besnoitia and Neospora species. Finally, cross-reactions with antibodies directed
      against other species of Sarcocystis might explain the positive reactions against
      the S. neurona antigens.

PMID- 28490376
TI  - The effects of clinical supervision on supervisees and patients in cognitive
      behavioral therapy: a study protocol for a systematic review.
AB  - BACKGROUND: Clinical supervision by a senior therapist is a very common practice
      in psychotherapist training and psychiatric care settings. Though clinical
      supervision is advocated by most educational and governing institutions, the
      effects of clinical supervision on the supervisees' competence, e.g., attitudes,
      behaviors, and skills, as well as on treatment outcomes and other patient
      variables are debated and largely unknown. Evidence-based practice is advocated
      in clinical settings but has not yet been fully implemented in educational or
      clinical training settings. The aim of this systematic review is to synthesize
      and present the empirical literature regarding effects of clinical supervision in
      cognitive-behavioral therapy. METHODS: This study will include a systematic
      review of the literature to identify studies that have empirically investigated
      the effects of supervision on supervised psychotherapists and/or the supervisees'
      patients. A comprehensive search strategy will be conducted to identify published
      controlled studies indexed in the MEDLINE, EMBASE, PsycINFO, and Cochrane Library
      databases. Data on supervision outcomes in both psychotherapists and their
      patients will be extracted, synthesized, and reported. Risk of bias and quality
      of the included studies will be assessed systematically. DISCUSSION: This
      systematic review will rigorously follow established guidelines for systematic
      reviews in order to summarize and present the evidence base for clinical
      supervision in cognitive-behavioral therapy and may aid further research and
      discussion in this area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016046834.

PMID- 28490377
TI  - Cochlear implant electrode sealing techniques and related intracochlear pressure
      changes.
AB  - BACKGROUND: The inserted cochlear implanted electrode is covered at the site of
      the round window or cochleostomy to prevent infections and leakage. In a
      surgically hearing preservational concept, low intracochlear pressure changes are
      of high importance. The aim of this study was to observe intracochlear pressure
      changes due to different sealing techniques in a cochlear model. METHODS:
      Cochlear implant electrode insertions were performed in an artifical cochlear
      model and the intracochlear pressure changes were recorded in parallel with a
      micro-pressure sensor positioned in the apical region of the cochlea model to
      follow the maximum amplitude of intracochlear pressure. Four different sealing
      conditions were compared: 1) overlay, 2) overlay with fascia pushed in, 3) donut
      like fascia ring, 4) donut-like fascia ring pushed in. RESULTS: We found
      statistically significant differences in the occurrence of maximum amplitude of
      intracochlear pressure peak changes related to sealing procedure comparing the
      different techniques. While the lowest amplitude changes could be observed for
      the overlay technique (0.14 mmHg +/- 0.06) the highest values could be observed
      for the donut-like pushed in technique (1.79 mmHg +/- 0.69). CONCLUSION: Sealing
      the electrode inserted cochlea can lead to significant intracochlear pressure
      changes. Pushing in of the sealing tissue cannot be recommended.

PMID- 28490375
TI  - Structural and electrophysiological dysfunctions due to increased endoplasmic
      reticulum stress in a long-term pacing model using human induced pluripotent stem
      cell-derived ventricular cardiomyocytes.
AB  - BACKGROUND: Long-term ventricular pacing has deleterious effects and becomes more
      significant when cumulative percent ventricular pacing (Cum%VP) exceeds 40% of
      time. However, cellular disturbances and pathways by which pacing leads to
      myocardial disorders are not well understood. Attempts to resolve these questions
      have been hampered by difficulties in obtaining human cardiac tissue and the
      inability to build a longer-lasting (lasting longer than weeks) pacing model in
      vitro. METHODS: Human induced pluripotent stem cell-derived ventricular
      cardiomyocytes (VCMs) were cultured in the presence of electrical stimulation for
      2 weeks. Quantitative structural and electrophysiological analyses were used to
      define the functional disturbances of pacing. RESULTS: Compared to controls,
      paced VCMs exhibited a remarkable reduction in the contractile protein
      expression, an increased apoptosis ratio and electrophysiological remodelling in
      a Cum%VP-dependent manner. Investigation of the protein expression levels
      revealed that long-term pacing universally activated both ER stress and
      downstream calpain. Moreover, the inhibition of calpain attenuated the adverse
      effects on the structural remodelling and increased the ICa, L in paced VCMs.
      CONCLUSIONS: The results demonstrated that pacing VCMs for 2 weeks in vitro led
      to a series of structural and electrophysiological dysfunctions. The increased ER
      stress and downstream calpain could be a central mechanism underlying the disease
      pathogenesis. This finding could represent a new therapeutic target in the
      management of long-term pacing patients.

PMID- 28490378
TI  - Parotidectomy using the Harmonic scalpel: ten years of experience at a rural
      academic health center.
AB  - BACKGROUND: Parotidectomy is one of the most commonly performed procedures by
      otorhinolaryngologists. Traditionally dissection is performed with a combination
      of a steel scalpel and bipolar cautery; however, starting in the early 2000s, the
      Harmonic scalpel has provided an alternative method for dissection and
      hemostasis. The purpose of this study is to compare operative time, blood loss,
      complications, and cost between the Harmonic scalpel and steel scalpel plus
      bipolar cautery for superficial and total parotidectomy. METHODS: Retrospective
      cohort of patients who underwent superficial or total parotidectomy with the
      Harmonic or cold steel between 2000 and 2015. Across 255 patients, comparison
      between operative time, blood loss, complications, and cost was performed.
      RESULTS: Superficial parotidectomy was performed on 120 patients with the
      Harmonic and 54 with steel scalpel. Total parotidectomy was performed on 59
      patients using the Harmonic and 22 patients with cold steel. For superficial
      parotidectomy, the Harmonic reduced operative time (216 +/- 42 vs. 234 +/- 54
      min, p = 0.03) and decreased blood loss (28 +/- 19 vs. 76 +/- 52 mls, p < 0.05).
      With total parotidectomy the Harmonic decreased operative time (240 +/- 42 vs.
      288 +/- 78 min, p = 0.01) and reduced blood loss (38 +/- 21 mls vs. 85 +/- 55
      mls, p < 0.05). There were no differences in complication rates between groups.
      Harmonic use was associated with surgical cost reduction secondary to reduced
      operative times. CONCLUSIONS: The Harmonic scalpel decreases blood loss and
      operating time for superficial and total parotidectomy. Shorter operative times
      may decrease the overall cost of parotidectomy.

PMID- 28490380
TI  - Living with hypertrophic cardiomyopathy and an implantable defibrillator.
AB  - BACKGROUND: ICDs efficiently terminate life-threatening arrhythmias, but
      complications occur during long-term follow-up. Patients' own perspective is
      largely unknown. The aim of the study was to describe experiences of hypertrophic
      cardiomyopathy (HCM) patients with implantable defibrillators (ICDs). METHODS: We
      analyzed 26 Swedish patient interviews using hermeneutics and latent content
      analysis. RESULTS: Patients (aged 27-76 years) were limited by HCM especially if
      it deteriorates into heart failure. The ICD implies safety, gratitude, and is
      accepted as a part of the body even when inappropriate ICD shocks are
      encountered. Nobody regretted the implant. Both the disease and the ICD affected
      professional life and leisure time activities, especially at younger ages. Family
      support was usually strong, but sometimes resulted in overprotection, whereas
      health care focused on medical issues. Despite limitations, patients adapted,
      accepted, and managed challenges. CONCLUSION: HCM patients with ICDs reported
      good spirit and hope even though they had to adapt and accept limitations over
      time.

PMID- 28490379
TI  - A novel scoring system for predicting the neurologic prognosis prior to the
      initiation of induced hypothermia in cases of post-cardiac arrest syndrome: the
      CAST score.
AB  - BACKGROUND: The aim of this study was to develop a scoring system for identifying
      the post-cardiac arrest syndrome (PCAS) patients with a good potential for
      recovery prior to the initiation of induced therapeutic hypothermia. METHODS: A
      multi-center, retrospective, observational study was performed. Data of a total
      of 151 consecutive adults who underwent induced hypothermia after cardiac arrest
      (77 learning cases from two hospitals and 74 validation cases from two other
      hospitals) were analyzed. RESULTS: In the learning set, 8 factors (initial
      rhythm, witnessed status and time until return of spontaneous circulation, pH,
      serum lactate, motor score according to the Glasgow Coma Scale (GCS), gray matter
      attenuation to white matter attenuation ratio (GWR), serum albumin, and
      hemoglobin) were found to be strongly correlated with the neurological outcomes.
      A tentative scoring system was created from the learning data using these
      factors, and the predictive accuracy (sensitivity and specificity) was evaluated
      in terms of both internal validation (0.85 and 0.84) and external validation
      (cutoff 50%: 0.95 and 0.90, 30%: 0.87 and 0.98, 15%: 0.67 and 1.00). Finally,
      using all the data, we established a post-Cardiac Arrest Syndrome for induced
      Therapeutic hypothermia (CAST) score to predict the neurologic prognosis prior to
      initiation of induced hypothermia. CONCLUSIONS: The CAST score was developed to
      predict the neurological outcomes of PCAS patients treated by induced
      hypothermia. The likelihood of good recovery at 30 days was extremely low in PCAS
      patients with a CAST score of <=15%. Prospective validation of the score is
      needed in the future.

PMID- 28490381
TI  - Palliative care in the neonatal unit: neonatal nursing staff perceptions of
      facilitators and barriers in a regional tertiary nursery.
AB  - BACKGROUND: Neonatology has made significant advances in the last 30 years.
      Despite the advances in treatments, not all neonates survive and a palliative
      care model is required within the neonatal context. Previous research has focused
      on the barriers of palliative care provision. A holistic approach to enhancing
      palliative care provision should include identifying both facilitators and
      barriers. A strengths-based approach would allow barriers to be addressed while
      also enhancing facilitators. The current study qualitatively explored perceptions
      of neonatal nurses about facilitators and barriers to delivery of palliative care
      and also the impact of the regional location of the unit. METHODS: The study was
      conducted at the Townsville Hospital, which is the only regional tertiary
      neonatal unit in Australia. Semi-structured interviews were conducted with a
      purposive sample of eight neonatal nurses. Thematic analysis of the data was
      conducted within a phenomenological framework. RESULTS: Six themes emerged
      regarding family support and staff factors that were perceived to support the
      provision of palliative care of a high quality. Staff factors included
      leadership, clinical knowledge, and morals, values, and beliefs. Family support
      factors included emotional support, communication, and practices within the unit.
      Five themes emerged from the data that were perceived to be barriers to providing
      quality palliative care. Staff perceived education, lack of privacy, isolation,
      staff characteristics and systemic (policy, and procedure) factors to impact upon
      palliative care provision. The regional location of the unit also presented
      unique facilitators and barriers to care. CONCLUSIONS: This study identified and
      explored facilitators and barriers in the delivery of quality palliative care for
      neonates in a regional tertiary setting. Themes identified suggested that a
      strengths-approach, which engages and amplifies facilitating factors while
      identified barriers are addressed or minimized, would be successful in supporting
      quality palliative care provision in the neonatal care setting. Study findings
      will be used to inform clinical education and practice.

PMID- 28490383
TI  - Erratum to: chTLR4 pathway activation by Astragalus polysaccharide in bursa of
      Fabricius.

PMID- 28490382
TI  - Premarital HIV testing in Malaysia: a qualitative exploratory study on the views
      of major stakeholders involved in HIV prevention.
AB  - BACKGROUND: HIV screening has existed in numerous methods as an important part of
      HIV prevention efforts over the years. Premarital HIV testing for couples who
      wish to marry has been implemented in a number of regions, which often operate in
      a mandatory rather than voluntary basis and is considered a contentious issue,
      with viewpoints held in favour and against. One such region is Malaysia which has
      a policy of mandatory premarital HIV testing of prospective Muslim married
      couples. The purpose of this study is to understand stakeholders' views on
      premarital HIV testing given the Malaysian Islamic context. METHODS: 35 in-depth
      face to face semi-structured interviews were undertaken with key stakeholder
      groups involved in HIV prevention policy in Malaysia, namely, officials from the
      Ministry of Health, religious leaders and people living with HIV. Participants
      were recruited from the Klang Valley area, from July to December 2013, using
      purposive sampling techniques. Inclusion criteria necessitated that participants
      were over the age of 18 and provided full consent. Interviews were audiotaped,
      followed a standardised topic guide, transcribed verbatim and analysed using a
      framework analysis. RESULTS: Participants identified pre-marital HIV testing as
      an effective HIV prevention policy implemented in Malaysia and was viewed, for
      the most part, as a positive initiative across all stakeholders. Religious
      leaders were supportive of testing as it provides a protective mechanism, in line
      with the teachings of the Shariah, while Ministry of Health officials considered
      it a normal part of their HIV prevention screening initiatives. However, there
      were concerns surrounding issues such as confidentiality, counselling and
      discrimination surrounding the test described by the PLHIV group. CONCLUSION: The
      findings of this study show that among the participants interviewed was strong
      support for mandatory premarital HIV testing, which could possibly expose the
      vulnerability to HIV, reluctance to test and other areas in the HIV response in
      Malaysia that need to be addressed. Furthermore, although international health
      organisations are vehemently against mandatory premarital HIV testing, the strong
      local support for such measures and the mismatch between these views is worth
      exploring in more detail, given the cultural, social and religious context.

PMID- 28490384
TI  - Neuroendocrine carcinoma of the breast: a review of 126 cases in China.

PMID- 28490385
TI  - ALK-positive anaplastic large cell lymphoma undiagnosed in a patient with
      tuberculosis: a case report and review of the literature.
AB  - BACKGROUND: Due to a similarity between the features of lymphoma and the features
      of tuberculosis, lymphoma may go unrecognized and undiagnosed in patients with
      tuberculosis. CASE PRESENTATION: A 33-year-old Thai man presented to our center
      with typical clinical manifestations of tuberculous lymphadenitis, with negative
      tests for both acid-fast bacilli and fungi, and negative polymerase chain
      reaction for Mycobacterial tuberculosis complex. The disease was not responding
      to anti-tuberculosis treatment and he developed both pericardial effusion and
      progressive lymphadenopathy. Large lymphoma cells were evident in the pericardial
      effusion, and a review of the previous lymph node biopsies confirmed the
      existence of ALK-positive anaplastic large cell lymphoma and tuberculous
      lymphadenitis. Moreover, when the tests were repeated, he was found to be
      positive for both acid-fast bacilli and Mycobacterial tuberculosis complex. The
      presence of typical morphology of tuberculous lymphadenitis and inattentional
      blindness may explain why the presence of large lymphoma cells was overlooked in
      one of the previous lymph node biopsies. Our patient developed severe pneumonia
      with profound septic shock due to carbapenem-resistant Enterobacteriaceae and
      died within days. CONCLUSIONS: Given that tuberculosis and lymphoma can share
      common features, this case highlights the importance of thoroughly reviewing all
      foregoing relevant patient data (most notably pathology samples) in order to rule
      out the presence of lymphoma that may exist within the shadow of typical
      morphology of tuberculous lymphadenitis.

PMID- 28490386
TI  - Pharmacists' Familiarity with and Institutional Utilization of Rapid Diagnostic
      Technologies for Antimicrobial Stewardship.
AB  - Rapid diagnostic technologies (RDTs) significantly reduce organism identification
      time and can augment antimicrobial stewardship program (ASP) activities. An
      electronic survey quantified familiarity with and utilization of RDTs by clinical
      pharmacists participating in ASPs. Familiarity was highest with polymerase chain
      reaction (PCR). Formal infectious diseases training was the only significant
      factor influencing RDT familiarity. Infect Control Hosp Epidemiol 2017;38:863
      866.

PMID- 28490387
TI  - Serum carotenoid and retinol levels in African-Caribbean Tobagonian men with high
      prostate cancer risk in comparison with African-American men.
AB  - Black men are known to have a higher risk for prostate cancer (PC). Carotenoids
      and retinol, linked to PC, have not been compared in different black populations
      at risk. We examined serum carotenoid and retinol levels between PC-free African
      Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic
      intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and
      African-American (AA) men with elevated serum prostate-specific antigen (PSA)
      levels (>=4 ng/ml). AC men who participated in the 2003 lycopene clinical trial
      and AA men who participated in the 2001-2006 National Health and Nutrition
      Examination Survey were compared. Serum specimens were analysed for carotenoid
      (beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin and
      lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to
      examine the association between serum carotenoid and retinol levels and black
      ethnicity, overall and among men with elevated serum PSA. There were sixty-nine
      AC men and sixty-five AA men, aged 41-79 years, included. AC men were associated
      with lower serum lycopene and retinol levels, and higher serum alpha- and beta
      carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for
      age, BMI, ever smoked cigarettes, education and hypertension (P<=0.03). Among men
      with elevated PSA, serum retinol was no longer statistically significant with
      ethnicity (P=0.06). Possible differences may be attributed to dietary intake,
      genetics and/or factors that influence bioavailability of these micronutrients.
      Prospective studies are warranted that investigate whether these differences in
      micronutrients between AC Tobagonian and AA men influence PC risk.

PMID- 28490388
TI  - The ability of ewes with lambs to learn a virtual fencing system.
AB  - The Nofence technology is a GPS-based virtual fencing system designed to keep
      sheep within predefined borders, without using physical fences. Sheep wearing a
      Nofence collar receive a sound signal when crossing the virtual border and a weak
      electric shock if continuing to walk out from the virtual enclosure. Two
      experiments testing the functionality of the Nofence system and a new learning
      protocol is described. In Experiment 1, nine ewes with their lambs were divided
      into groups of three and placed in an experimental enclosure with one Nofence
      border. During 2 days, there was a physical fence outside the border, during Day
      3 the physical fence was removed and on Day 4, the border was moved to the other
      end of the enclosure. The sheep received between 6 and 20 shocks with an average
      of 10.9+/-2.0 (mean+/-SE) per ewe during all 4 days. The number of shocks
      decreased from 4.38+/-0.63 on Day 3 (when the physical fence was removed) to
      1.5+/-0.71 on Day 4 (when the border was moved). The ewes spent on average 3%,
      6%, 46% and 9% of their time outside the border on Days 1, 2, 3 and 4,
      respectively. In Experiment 2, 32 ewes, with and without lambs, were divided into
      groups of eight and placed in an experimental enclosure. On Day 1, the enclosure
      was fenced with three physical fences and one virtual border, which was then
      increased to two virtual borders on Day 2. To continue to Day 3, when there was
      supposed to be three virtual borders on the enclosure, at least 50% of the ewes
      in a group should have received a maximum of four shocks on Day 2. None of the
      groups reached this learning criterion and the experiment ended after Day 2. The
      sheep received 4.1+/-0.32 shocks on Day 1 and 4.7+/-0.28 shocks on Day 2. In
      total, 71% of the ewes received the maximum number of five shocks on Day 1 and
      77% on Day 2. The individual ewes spent between 0% and 69.5% of Day 1 in the
      exclusion zone and between 0% and 64% on Day 2. In conclusion, it is too
      challenging to ensure an efficient learning and hence, animal welfare cannot be
      secured. There were technical challenges with the collars that may have affected
      the results. The Nofence prototype was unable to keep the sheep within the
      intended borders, and thus cannot replace physical fencing for sheep.

PMID- 28490389
TI  - Monitoring and mass-trapping methodologies using pheromones: the lesser date moth
      Batrachedra amydraula.
AB  - The lesser date moth (LDM) Batrachedra amydraula is a significant pest of date
      palm fruits. Previously, detection and monitoring of the pest was inaccurate due
      to high costs of sampling with lifting machines. We report a practical system for
      detection and monitoring of LDM based on pheromone traps and relevant models.
      Dose-response experiments with LDM pheromone traps indicated a 1 mg lure is
      optimal for monitoring. Delta traps with adhesive covering their entire inner
      surface gave the highest captures while trap colour was unimportant. Sampling
      pheromone traps throughout the night indicated male flight began at 1:00-2:00 and
      reached a peak 2 h before sunrise. Monitoring traps exposed all year long in
      Israel revealed three generations with different abundance. Trapping transects in
      a date plantation indicated interference from a monitoring trap became minimal at
      distances >27 m away. Inter-trap distances closer than this may lower efficiency
      of monitoring and mass trapping in control programs. Our estimate of the circular
      effective attraction radius (EARc) of a 1 mg delta trap for LDM (3.43 m) shows
      this bait is among the most attractive compared with baits for other insects. We
      developed encounter-rate equations with the pheromone trap EARc to model the
      interplay between population levels, trap density and captures that are useful
      for detection of invasive LDM and its control by mass trapping. The integrated
      methodologies are applicable to many pest species.

PMID- 28490390
TI  - Development and Evaluation of Acceptance and Commitment Therapy Delivered by
      Psychologists and Non-Psychologists in an NHS Community Adult Mental Health
      Service: a Preliminary Analysis.
AB  - BACKGROUND: Previous studies have demonstrated that acceptance and commitment
      therapy (ACT) is effective for depression and may be useful for complex
      transdiagnostic clients. AIMS: To conduct a preliminary evaluation of whether ACT
      is feasible and effective when delivered by psychologists and non-psychologists
      for complex clients in a National Health Service (NHS) community mental health
      service for adults. METHOD: Staff were trained in ACT and conducted one-to-one
      therapy with clients. Measures on general mental health, depression, fusion and
      values were given pre-therapy, post-therapy and at 3-month follow-up. RESULTS:
      Standardized measures showed significant improvements post-therapy for global
      mental health, depression, cognitive fusion and values post-treatment. These were
      partially maintained at follow-up and remained after an intent-to-treat analysis.
      There were no differences in outcomes between psychologists and non
      psychologists. CONCLUSIONS: ACT may be delivered effectively with limited
      training for complex cases in secondary care, though further research is needed.

PMID- 28490391
TI  - MicroRNA-499-5p regulates porcine myofiber specification by controlling Sox6
      expression.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate
      gene expression of target messenger RNAs (mRNAs) and miRNAs have been proven to
      play vital roles in skeletal muscle development. The miRNA-499-5p has been
      reported to be negatively related with the expression of Sox6, a critical
      transcription factor for the maintenance of fast-twitch skeletal muscle. In this
      study, we amplified a length of 2012-bp mRNA that contains a 1512-bp porcine Sox6
      (pSox6) 3'UTR from skeletal muscle of a Duroc*Landrace*Yorkshire pig. By
      luciferase reporter assay we verified that pSox6 is a target of miR-499-5p. In
      extensor digitorum longus and Soleus muscles of pigs, the expression levels of
      miR-499-5p and pSox6 mRNA were also inversely correlated. Besides, overexpression
      of miR-499-5p in porcine satellite cells promoted the expression of MyHC I and
      MyHC IIa mRNA, along with a reduction of pSox6 mRNA. Taken together, these
      results indicate that miR-499-5p may facilitate the oxidative myofibers formation
      by downregulating pSox6 expression.

PMID- 28490392
TI  - A systematic review of the heritability of specific psychopathic traits using
      Hare's two-factor model of psychopathy.
AB  - BACKGROUND: There have been no systematic reviews that investigated the
      heritability of the two-factor model of psychopathy: interpersonal-affective and
      behavioral. Our review aimed, first, to examine the heritability of general
      psychopathic traits and, second, if genetic influences were suggested, to
      determine the heritability of various traits related to the interpersonal
      affective and behavioral factors of psychopathy. METHOD: A systematic literature
      search was conducted using articles from the PsycINFO, Embase, Global Health,
      Medline, PubMed, Web of Science, and Scopus databases (January of 1980 to
      December of 2015) in order to identify eligible literature that reported on the
      heritability of psychopathy-related traits. Papers were also found via manual
      examination and reference tracking. Papers were subjected to exclusion criteria
      and quality appraisal. We identified a total of 24 studies. RESULTS: Our results
      were grouped into three categories: general, interpersonal-affective, and
      behavioral. All these areas demonstrated modest to high heritability. The highest
      heritability values were found in studies investigating callous-unemotional
      behaviors. CONCLUSIONS: Heritability was found for all the psychopathic traits.
      Future research should include endophenotypic approaches that explore gene
      environment correlations, which could aid in identification of the behavioral
      phenotype that is most amenable to early intervention by way of moderation of
      genetic risk.

PMID- 28490393
TI  - Assessing multiple goods and services derived from livestock farming on a nation
      wide gradient.
AB  - Livestock farming is an essential activity in many rural areas, where it
      contributes to the maintenance of soil fertility and farmland biodiversity, as
      well as to a set of social public goods including food security, rural vitality
      and culture. However, livestock sustainability assessments tend to focus
      primarily on environmental and economic dimensions; therefore, these valuations
      might be limited because they do not consider the complete set of associated
      goods and services (GS). Hence, a need exists to recognise the multiple
      contributions provided by livestock to human well-being and society. The
      objective of this study was to analyse the provision of multiple GS derived from
      livestock across regions in France and empirically demonstrate sets of GS that
      repeatedly appeared together. We designated these multiple GS provided by
      livestock as contributions to productive, environmental, rural vitality and
      cultural benefits that human populations derive directly or indirectly from
      livestock agroecosystems. First, we combined expert knowledge with results of a
      literature review to define a bundle of GS provided by livestock. We then
      described indicators that quantified each good or service and screened national
      databases to determine the availability of supporting data. Finally, we assessed
      the GS and their relationships (synergies or trade-offs) on a nation-wide
      gradient in France at the department level (Nomenclature of Territorial Units for
      Statistics 3). Four main categories of GS were considered: provisioning (e.g.
      food quantity and quality), environmental quality (e.g. biodiversity, landscape
      heterogeneity, water quality), rural vitality (e.g. employment, rural dynamism)
      and culture (e.g. gastronomy and landscape heritage). Four major types of GS
      bundles were identified, which suggested strong contrasts among French rural
      areas in terms of the nature of the GS that occurred together and their levels of
      provision. GS bundles in France had a non-random spatial distribution. This study
      represents an initial step towards developing a methodology to consider GS
      bundles provided by livestock. Nonetheless, further research is needed to
      understand socio-economic, environmental, political and geographic determinants
      of the composition of GS bundles.

PMID- 28490394
TI  - Synbiotic supplementation and the effects on clinical and metabolic responses in
      patients with rheumatoid arthritis: a randomised, double-blind, placebo
      controlled trial.
AB  - Synbiotic intake may be associated with reduced inflammation in patients with
      rheumatoid arthritis (RA) due to optimised inflammatory markers, oxidative stress
      and insulin resistance. This research was conducted to assess the effects of
      synbiotic supplementation on the clinical and metabolic parameters of patients
      with RA. A total of fifty-four patients with RA were allocated into two groups to
      receive either a synbiotic capsule (n 27) or a placebo (n 27) for 8 weeks in this
      randomised, double-blind, placebo-controlled trial. Fasting blood samples were
      taken at baseline and week 8 of the study to quantify related markers. After the
      8-week intervention, compared with the placebo, synbiotic supplementation
      resulted in a significant reduction in serum high-sensitivity C-reactive protein
      (hs-CRP) levels (-1427.8 (sd 3267.2) v. +2833.4 (sd 5639.7) ng/ml, P=0.001). In
      addition, compared with the placebo, synbiotic supplementation improved disease
      activity score-28 joints (DAS-28) (-1.6 (sd 0.8) v. -0.3 (sd 0.5), P<0.001) and
      visual analogue scales (VAS) pain (-30.4 (sd 18.7) v. -11.5 (sd 15.9), P<0.001).
      In addition, a significant elevation in plasma nitric oxide (NO) (+0.8 (sd 4.4)
      v. -2.6 (sd 4.5) umol/l, P=0.008), and significant reductions in insulin values (
      13.8 (sd 26.4) v. +4.2 (sd 28.2) pmol/l, P=0.01), homoeostasis model of
      assessment-estimated insulin resistance (HOMA-IR) (-0.5 (sd 1.0) v.+0.1 (sd 1.1),
      P=0.03) and homoeostatic model assessment-beta-cell function (HOMA-B) (-9.4 (sd
      17.9) v. +3.3 (sd 18.9), P=0.01) following supplementation with the synbiotic
      compared with the placebo. Compared with the placebo, synbiotic supplementation
      also resulted in a significant increase in plasma GSH (+36.6 (sd 63.5) v. -58.5
      (sd 154.4) umol/l, P=0.005). Overall, our study demonstrated that synbiotic
      supplementation for 8 weeks among patients with RA had beneficial effects on hs
      CRP, DAS-28, VAS, NO, insulin levels, HOMA-IR, HOMA-B and GSH levels.

PMID- 28490395
TI  - Factors associated with pre-slaughter mortality in turkeys and end of lay hens.
AB  - Pre-slaughter transportation may affect poultry welfare and mortality rates. A
      retrospective analysis was conducted to examine the effect of environmental,
      management and individual factors on the percentage of dead birds during pre
      slaughter transportation (dead-on-arrival, DOA). The variables accounted for in
      the analyses included: environmental temperature, travel duration, genetic line,
      gender, crate type and crate stocking density. Among the 41 452 loads of turkeys
      (34 696 388 birds) and 3241 of end of lay hens (21 788 124 birds) transported to
      three large abattoirs in northern Italy in a 3-year period, the median DOA was
      0.14% in turkeys, and 0.38% in hens. In turkeys, travel duration longer than 30
      min, temperature higher than 26 degrees C and high in-crate densities were
      associated with increased DOA. In winter (?2 degrees C), high stocking densities
      did not reduce the mortality risk from cold stress; on the contrary, for stocking
      densities either near to or just above the maximum density in EC Reg. 1/2005, the
      DOA risk was greater than for loads with densities of 10 kg/m2 less than the EC
      maximum. Male birds and specific genetic lines also showed a higher DOA. In hens,
      transportation lasting longer than 2 h and the brown-feathered breed were
      associated with higher DOA. Dead-on-arrival progressively increased with travel
      duration, remaining constant between 4 and 6 h and peaking at 8 h (median:
      0.57%). The maximum DOA increase was detected during winter. These results show
      that several species-specific factors may lead to increased risk of mortality.

PMID- 28490396
TI  - Prognostic factors for therapeutic sialendoscopy.
AB  - OBJECTIVE: To review our experience with therapeutic sialendoscopy in both the
      submandibular and parotid glands in order to determine prognostic factors and
      improve successful outcomes. STUDY DESIGN: Single-centre, retrospective chart
      review. METHOD: The medical records of patients who had undergone sialendoscopy
      for sialolithiasis were reviewed, and demographic details, stone data (location,
      size, multiplicity, mobility), and operative technique and success were recorded.
      RESULTS: Eighty-five patients were included: 70 patients with submandibular
      stones and 15 with parotid stones. Sialendoscopy was successful in all cases.
      Complete endoscopic removal was successful in 51 per cent of patients with
      submandibular stones and 47 per cent of those with parotid stones. Size (less
      than 5 mm) and distance from the papilla (less than 3 cm) were significant
      factors affecting success for patients with submandibular duct stones. However,
      this was not the case for patients with parotid duct stones, with neither
      variable achieving significance; nevertheless, numbers were small. CONCLUSION:
      Stone size and location significantly affect the success of therapeutic
      sialendoscopy in submandibular glands.

PMID- 28490398
TI  - The microscope and the endoscope.

PMID- 28490397
TI  - Aortic dissection and cystinosis: is there any relationship?
AB  - Cystinosis is a rare, autosomal-recessive genetic disorder. The kidneys are
      commonly involved, as there is cystinosin protein malfunction, and nephropathic
      cystinosis ensues. Although cardiac and vascular involvements are rare, we
      describe a unique case of aortic dissection in a 25-year-old female with
      cystinosis. We discuss the possible aetiologies of aortic dissection in this
      condition.

PMID- 28490399
TI  - Specific immunoglobulin E and immunoglobulin G4 toward major allergens of house
      dust mite during allergen-specific immunotherapy.
AB  - BACKGROUND: Specific immunoglobulin E (sIgE) and sIgG4 to house-dust mite (HDM)
      major allergens during allergen immunotherapy (AIT) and their clinical relevance
      remain unclear. OBJECTIVE: To investigate the variation of sIgE and sIgG4 to HDM
      major allergens and the correlation with clinical responses during AIT in
      patients with allergic rhinitis. METHODS: Thirty-nine patients with HDM allergy
      were divided into the AIT group (taking immunotherapy) and the control group
      (medication only use). The AIT group was subdivided into negative clinical
      responses to AIT (nAIT) group and positive clinical responses to AIT (pAIT) group
      according to symptom relief and subjective evaluation. sIgE and sIgG4 to
      Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), and their
      group 1 and group 2 major allergens (Dp1, Df1, Dp2, and Df2) were measured before
      AIT, at 6 months, and at 1 year after starting AIT. RESULTS: Dp2, Df, and Df2
      sIgE values decreased significantly in the pAIT group versus the nAIT group after
      1 year of AIT (median values of delta change were Dp2, -10.09 versus 5.89 kU/L, p
      = 0.001; median values of Df were -9.69 versus 17.54 kU/L, p = 0.004; median
      values of Df2 were -11.06 versus 20.08 kU/L, p = 0.013). There was a robust
      increase in the sIgG4 values to Dp, Df, and their major allergens in both the
      pAIT and the nAIT groups overall after 1 year of treatment. CONCLUSION: Patients
      with a positive response to AIT showed a significant reduction of HDM group 2
      sIgEs compared with those with a negative response to AIT, which indicated that a
      decrease in group 2 sIgEs could be a marker that reflected AIT clinical efficacy.

PMID- 28490400
TI  - Association of pediatric allergic rhinitis with the ratings of attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Allergic rhinitis (AR) is currently the most prevalent allergic
      disease in children and adolescents. OBJECTIVE: Surveys conducted by population
      based studies of East Asia revealed an increased prevalence of behavioral
      disorders in patients with AR. Thus, in this study, we explored the prevalence of
      attention-deficit/hyperactivity disorder (ADHD) in pediatric patients with AR.
      METHODS: A total of 333 children (6-12 years of age) with AR and a total of 322
      age-matched controls were included in this study. An otorhinolaryngologist
      diagnosed all AR cases and evaluated the severity of the disease. Skin-prick test
      results for 18 major allergens, Paediatric Rhinoconjunctivitis Quality of Life
      Questionnaire (PRQLQ), Child Behavior Checklist (CBCL), and Swanson, Nolan, and
      Pelham version IV (SNAP-IV) scores were recorded. RESULTS: In total, 320 age
      matched controls and 323 children with AR completed the study. With respect to
      the Total Nasal Symptom Score and the PRQLQ, the condition of the experimental
      group was more serious than that of the controls. The scores on the
      hyperactivity/impulsivity and inattention subscales, which evaluate ADHD
      symptoms, and those on the CBCL subscales were significantly higher in patients
      with AR than in the controls (all p values were <0.01). From the results of the
      Pearson correlation, we deduced that there were significant positive correlations
      between the AR-related data and each subscale of the CBCL and SNAP-IV in the AR
      group. Moreover, two basic characteristics (males and environmental exposure to
      tobacco smoke) present significant positive and age showed a significant negative
      correlations affect ADHD symptom in both the AR group and the control group.
      Also, in the "pure AR" group, hierarchical regression analyses were performed to
      determine the subtests of the PRQLQ, which are significant predictors of SNAP-IV
      and CBCL. CONCLUSIONS: Apart from AR per se, the possible comorbidities of
      impulsivity and inattention are important when managing children with AR. It is
      essential to evaluate the symptoms of ADHD in children and adolescents with AR.

PMID- 28490402
TI  - International Frontal Sinus Anatomy Classification and anatomic predictors of low
      lying anterior ethmoidal arteries.
AB  - BACKGROUND: The International Frontal Sinus Anatomy Classification (IFAC) was
      introduced to more accurately characterize ethmoid and frontal sinus
      pneumatization patterns. The prevalence of IFAC cells and their anatomic
      associations have not been described. OBJECTIVE: The goal was to examine the
      prevalence of IFAC cells and determine radiologic features associated with a low
      lying anterior ethmoidal artery (LAEA). METHODS: Imaging of adult patients who
      underwent computed tomographies from January 2015 to March 2016 were
      retrospectively reviewed by using the IFAC classification. We also measured the
      distance from the skull base to the anterior ethmoidal artery (AEA), the height
      of the lateral lamella of the cribriform plate, and anterior-posterior diameter
      from the anterior wall of the frontal sinus to the skull base (APF). Patients
      with a history of sinus surgery, trauma, malignancy, or congenital anomaly were
      excluded. Statistical analysis was performed by using Pearson correlation
      coefficients and chi2 tests. RESULTS: A total of 95 patients met the inclusion
      criteria. There was a significant association between supraorbital ethmoid cells
      and an LAEA (p < 0.001), with a significant effect size (phi = 0.276, p = 0.007).
      An inverse relationship was observed between Keros type I classification I and an
      LAEA (p < 0.001), with a significant effect size (phi = -0.414, p = 0.000).
      Significant associations were found between the AEA distance from the skull base
      and the cribriform lateral lamella height (R = 0.576, p < 0.001). In addition,
      there was a significant association between the AEA distance from the skull base
      and the APF (R = 0.497, p < 0.001). CONCLUSION: The presence of a supraorbital
      ethmoid cell and a wide APF were associated with an LAEA. There was a significant
      relationship between Keros type I classification and the AEA adjacent to the
      skull base. Delineation of these anatomic relationships may be helpful during
      endoscopic sinus surgery to avoid complications.

PMID- 28490401
TI  - Immunopathologic characteristics of nasal polyps in adult Koreans: A single
      center study.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (NP) (CRSwNP) is classified
      into eosinophilic and noneosinophilic types based on the level of tissue
      eosinophilia. The immunopathologic features of Western and Asian CRSwNP differ.
      OBJECTIVES: The aim of this study was to investigate the immunopathologic
      characteristics of Korean patients with eosinophilic NP versus noneosinophilic NP
      and those with atopic NP versus nonatopic NP. METHODS: Tissue samples were
      collected from 81 patients with NP and 24 controls. The clinical characteristics
      of all the patients were analyzed. Tissues were investigated for expression of
      chemical mediators, including interleukin (IL) 5, IL-10, IL-17, interferon-gamma,
      and tumor growth factor-beta1; transcription factors, including GATA binding
      protein 3 (GATA-3), forkhead box P3 (Foxp3), retinoic acid-related orphan
      receptor C (RORC), and T-box transcription factor (T-bet), and extracellular
      matrix, including collagen type I, fibronectin, tissue inhibitor of
      metalloproteinase 1, and matrix metalloproteinase (MMP) 9. RESULTS: Although the
      clinical characteristics differed between eosinophilic and noneosinophilic NPs,
      atopic status did not affect the clinical findings of CRSwNP. Both T-helper 1 and
      2 cytokines increased significantly in patients with eosinophilic NP, but atopic
      status did not affect the expression of any of the chemical mediators. GATA-3
      messenger RNA (mRNA) expression increased significantly in patients with
      eosinophilic NP, and RORC mRNA expression increased significantly in patients
      with noneosinophilic NP. T-bet, RORC, and Foxp3 mRNA expression increased
      significantly in patients with nonatopic NP. Fibronectin and MMP-9 mRNA
      expression increased significantly in patients with noneosinophilic NP, whereas
      only MMP-9 mRNA increased significantly in patients with eosinophilic and those
      with noneosinophilic NP. CONCLUSION: The immunopathologic characteristics
      differed between eosinophilic NP and noneosinophilic NP and between atopic NP and
      nonatopic NP. The different underlying pathogenic processes may influence the
      development of Korean NP.

PMID- 28490403
TI  - Effects of changes in nasal volume on voice in patients after endoscopic
      endonasal transsphenoidal surgery.
AB  - OBJECTIVE: To investigate a potential correlation between changes in voice and
      changes in nasal volume. METHODS: The endoscopic endonasal transsphenoidal
      approach (EETSA) was performed on 120 patients between February 2009 and August
      2016 by using the bilateral modified nasoseptal rescue flaps method. All the
      patients were subjected to pre- and postoperative paranasal computed tomography
      (CT) and voice evaluations by using acoustic analyses, a nasometer to measure the
      nasalance, and determination of the voice handicap index (VHI). Paranasal CT and
      the medical image processing software were used to calculate changes in nasal
      cavity volume in three nasal sections. RESULTS: Enlargement of the nasal cavity
      after surgery was evident in all three areas (anteronasal, p < 0.001; midnasal, p
      = 0.005; postnasal, p = 0.025). In addition, EETSA resulted in significantly
      higher mean nasalance scores for the oronasal passage (p < 0.001) and nasal
      passage (p < 0.001); more frequency perturbation (jitter) (p < 0.001) and
      amplitude perturbation (shimmer) (p < 0.001); and higher grade, roughness,
      breathiness, asthenia, and strain scores (p < 0.001), and VHI (p = 0.01).
      However, only changes in the nasal volume after EETSA correlated with postnasal
      hypernasality (r = 0.2; p = 0.029). CONCLUSION: Although changes in nasal volume,
      voice, and speech may develop after EETSA, we found that changes in nasal volume
      were not correlated with changes in any voice-quality measure. However, the
      postnasal cavity was the region most dramatically affected by EETSA, and
      postnasal volume changes after surgery may be associated with hypernasal speech.

PMID- 28490404
TI  - Causes of dacryocystorhinostomy failure: External versus endoscopic approach.
AB  - OBJECTIVES: To compare the causes of failure between external and endoscopic
      dacryocystorhinostomy (DCR) techniques for the treatment of lacrimal obstruction.
      STUDY DESIGN: A retrospective cohort study. METHODS: The study population
      consisted of 53 consecutive patients who underwent revision endoscopic DCR from
      2002 to 2013 for lacrimal duct obstruction. Identified causes of previous DCR
      failure were compared between patients whose initial surgery was performed
      through an external versus an endoscopic approach. RESULTS: Reasons for surgical
      failure after external (n = 21) versus endoscopic (n = 32) DCR included
      cicatricial closure of the internal lacrimal ostium (52.4 versus 53.1%; p =
      0.96), inadequate removal of bone overlying the lacrimal sac (23.8 versus 9.4%; p
      = 0.15), sump syndrome (9.5 versus 9.4%; p = 0.99), and intranasal adhesions (65
      versus 37.5%; p = 0.05). Adhesions that involved the middle turbinate were a
      particularly impactful cause of failure when the DCR was performed through an
      external versus the endoscopic approach (57.1 versus 28.1%; p = 0.04).
      Septoplasty was more likely to be needed at the time of revision surgery if the
      initial procedure was performed externally (71.1 versus 15.6%; p = 0.02).
      Surgical success rates for revision DCR were comparable between the groups (75.0%
      external versus 73.3% endoscopic; p = 0.90), with a mean follow-up of 12.7
      months. CONCLUSION: DCR failure associated with intranasal adhesions was more
      likely to occur when the surgery was performed through an external rather than an
      endoscopic approach. Endoscopic instrumentation allowed for identification and
      correction of intranasal pathology at the time of DCR, including an enlarged
      middle turbinate or a deviated septum, which may improve surgical outcome.

PMID- 28490405
TI  - Utility of early postoperative imaging after combined endoscopic and open ventral
      skull base surgery.
AB  - PURPOSE: Immediate postoperative imaging is frequently obtained after combined
      skull base surgery (SBS) with endoscopic endonasal and open transcranial
      approaches. The importance of early postoperative imaging for detecting
      complications in these patients is still debatable. In this study, we
      investigated the clinical utility of early postoperative imaging after combined
      SBS for determination of postoperative complications. METHODS: A retrospective
      chart analysis of 21 cases of combined SBS between 2009 and 2015 was performed.
      Data on postoperative computed tomography (CT) and magnetic resonance imaging
      (MRI), and the hospital course were collected. We separated interpretations of
      postoperative imaging into two groups: (1) when using the radiologist's
      interpretation alone, and (2) when using the surgeon's knowledge of the case in
      conjunction with imaging. RESULTS: Forty-two postoperative scans were obtained
      (21 CT, 21 MRI) within 48 hours of surgery. There was a significant statistical
      difference between imaging interpretation by surgeons and radiologists for CT
      interpretation only. For CT interpretation the true positive (TP), false positive
      (FP), true negative (TN), and false negative (FN) rates for radiologists (TP,
      0/21; FP, 6/21; TN, 11/21; FN, 4/21) slightly deviated from surgeons'
      interpretation (TP, 1/21 [p = 0.9999]; FP, 0/21 [p = 0.0207]; TN, 17/21 [p =
      0.1000]; FN, 3/21 [p = 1.000]). Rates for MRI interpretation by both groups were
      nearly identical, with no significant difference found. Overall, four patients
      experienced seven postoperative complications, which led to a complication rate
      of 19.0% (4/21). The patients exhibited clinical symptoms in all instances of
      postoperative complications that required further intervention. CONCLUSION: The
      benefit of early postoperative imaging to detect complications after combined SBS
      was limited. In this cohort of patients, positive imaging findings' effects on
      patient management were dictated by the presence of supporting clinical symptoms.

PMID- 28490406
TI  - Closure of nasal septal perforations with a polydioxanone plate and
      temporoparietal fascia in a closed approach.
AB  - BACKGROUND: Septal perforation closure is still often invasive and complex, with
      relatively low closure rates. OBJECTIVES: We aimed to provide the first results
      of a case series of 20 patients with nasal septal perforations who underwent
      septal perforation repair by both an open and a minimally invasive technique by
      using a graft that consisted of temporoparietal fascia and a polydioxanone (PDS)
      plate without mucosal flaps. Between 2014 and 2016, we tested, for the first
      time, the feasibility of the insertion of this graft via a hemitransfixion
      incision at our institution. The rationale for the closed approach was to avoid
      any visible nasal scars. We reported our results of both approaches. METHODS: The
      septal perforations were closed by insertion of a graft, which consisted of a
      0.25-mm PDS flexible plate enveloped by temporoparietal fascia, into the
      perforation. The insertion of the graft was performed either via a columellar
      incision (open approach) or via a cosmetically advantageous hemitransfixion
      incision (closed approach) in an underlay technique. No attempts were made to
      close the perforation by mucosal flap rotation and/or advancement. Protective
      silastic sheeting to both sides of the perforation provided fixation to the graft
      while natural mucosal healing occurred over the perforation in the course of 3 to
      8 weeks. RESULTS: Eighteen of 20 perforations were closed by mucosa at the last
      follow-up. The mean follow-up was 8.7 months. Thirteen patients had surgery via
      the closed approach. CONCLUSION: We showed, for the first time, that the
      insertion of a graft that consisted of a PDS flexible plate enveloped in
      temporoparietal fascia via a hemitransfixion incision was feasible and resulted
      in complete mucosal closure of nasal septal perforations in most patients. By
      performing the hemitransfixion incision, we avoided any visible nasal scars.

PMID- 28490407
TI  - The application of a free nasal floor mucoperiosteal graft in endoscopic sinus
      surgery.
AB  - BACKGROUND: Numerous reconstructive techniques and materials have been reported
      for repair of skull base defects, cerebrospinal fluid (CSF) leaks, and coverage
      of denuded bone, including pedicled vascularized flaps and free mucosal grafts.
      OBJECTIVE: This study described our technique of harvesting and transferring a
      free nasal floor mucoperiosteal graft and discussed our experience with the
      application of this technique. METHODS: A retrospective review of 19 patients
      (mean age, 53.7 years; 13 men, 6 women) treated with image-guided endoscopic
      sinus surgery for chronic rhinosinusitis or tumors. Intraoperative free mucosal
      graft repair was performed for large skull base defects after resection of skull
      base tumor (n = 7), CSF leak (n = 12), and iatrogenic CSF leak (n = 7). Repair
      was performed in an overlay or an underlay fashion, with a multilayer approach in
      cases of a large skull base defect. Patients underwent endoscopic assessment at 6
      days, 5 weeks, and 12 weeks after surgery for assessment of healing and of CSF
      leak. The patients were followed up for a mean of 8.7 months. RESULTS: Minimal
      crusting was identified at the donor site in all the patients at 6 days, with no
      evidence of CSF leak. In cases of exposed bone and/or mucosal stripping,
      hyperostosis at the recipient graft site was avoided. All the patients had
      complete healing at the donor site and the recipient site, with minimal morbidity
      at 5 and 12 weeks, and no evidence of recurrent CSF leak. CONCLUSION: The use of
      nasal floor mucoperiosteal free grafts in endoscopic surgery offered the
      advantage of ease of harvest, coverage of large defects, and multiple
      applications of use, with minimal donor-site morbidity.

PMID- 28490408
TI  - Endoscopic resection of sinonasal mucosal melanoma has comparable outcomes to
      open approaches.
AB  - BACKGROUND: Endoscopic endonasal resection (EER) of sinonasal mucosal melanoma
      (SMM) is a newer surgical alternative to traditional external and/or open
      resection (OR). Studies on long-term outcomes are necessary to validate EER for
      this aggressive sinonasal malignancy. OBJECTIVE: To compare outcomes of EER
      versus OR in SMM. METHODS: A case series of patients who underwent surgical
      resection of SMM at a tertiary-care institution (2000-2015) was studied
      retrospectively. Demographics, tumor site and stage, surgical approach, surgical
      margin status, local control, and survival were compared between those who
      underwent EER and OR. RESULTS: Twenty-two patients met inclusion criteria. Nine
      underwent EER and 13 underwent OR. The mean age in the EER and OR groups was
      similar, 78.7 and 72.3 years, respectively. Two-thirds of patients were women
      (EER, 66.7%; OR, 61.5%). The nasal cavity was the most common primary tumor site
      (EER, 77.8%; OR, 84.6%). The local tumor stage in both groups was similar, with
      the majority of cases being T4 (EER, 55.6%; OR, 61.5%; p = 0.99). Negative
      margins were achieved in all EERs and in 69.2% of ORs. Median follow-up was 25.0
      months for the overall group (range, 1.7-172.9 months), 32.6 months (range, 3.4
      58.7 months) for EER and 14.1 months (range, 1.7-172.9 months) for OR cohorts.
      The 5-year overall survival was statistically similar in both groups (EER, 53.3%;
      OR, 22.7%; p = 0.214) as was disease-free survival (EER, 55.6%; OR, 22.8%; p =
      0.178). Local control, however, was significantly higher in the EER cohort (EER,
      85.7%; OR, 37.6%; p = 0.026). CONCLUSION: In carefully selected patients with
      sinonasal melanoma, endoscopic surgery with an experienced team may offer
      comparable survival and improved local control over open surgery. Prospective,
      multicentered studies with larger cohorts are needed to validate these results.

PMID- 28490409
TI  - Endoscopic-guided coblation treatment of nasal telangiectasias in hereditary
      hemorrhagic telangiectasia: "How I do it".
AB  - INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal
      dominant disease that leads to frequent epistaxis. It can have a significant
      impact on quality of life. Many reports exist regarding various therapies to
      address the epistaxis. MATERIALS AND METHODS: We presented our technique for
      addressing the epistaxis associated with HHT. RESULTS: Patients are treated in
      the operating room while they are under general anesthesia. A local anesthetic is
      injected sublabially, and oxymetazoline is dripped into the nose. The coblation
      wand is used to treat the telangiectasias. Bevacizumab is then injected into the
      nasal cavity bilaterally. CONCLUSION: The coblation wand, with or without
      adjunctive bevacizumab injection, is a technically feasible intervention for
      patients with HHT that all providers can perform.

PMID- 28490410
TI  - Recurrence of Sinonasal Inverted Papilloma Following Surgical Approach: A Meta
      Analysis.

PMID- 28490411
TI  - Is the Counterweight Program a feasible and acceptable option for structured
      weight management delivered by practice nurses in Australia? A mixed-methods
      study.
AB  - Nurse-led weight management programs, like the Counterweight Program in the
      United Kingdom, may offer a way for Australian general practices to provide
      weight management support to adults who are overweight or obese. During
      Counterweight, nurses provide patients with six fortnightly education sessions
      and three follow-up sessions to support weight maintenance. This study examined
      the feasibility, acceptability and perceived value of the Counterweight Program
      in the Australian primary care setting using a mixed-methods approach. Six
      practice nurses, from three general practices, were trained and subsidised to
      deliver the program. Of the 65 patients enrolled, 75% (n=49) completed the six
      education sessions. General practitioners and practice nurses reported that the
      training and resource materials were useful, the program fitted into general
      practices with minimal disruption and the additional workload was manageable.
      Patients reported that the program created a sense of accountability and provided
      a safe space to learn about weight management. Overall, Counterweight was
      perceived as feasible, acceptable and valuable by Australian practice staff and
      patients. The key challenge for future implementation will be identifying
      adequate and sustainable funding. An application to publically fund Counterweight
      under the Medicare Benefits Schedule would require stronger evidence of
      effectiveness and cost-effectiveness in Australia.

PMID- 28490412
TI  - Improving community access to terminal phase medicines in Australia:
      identification of the key considerations for the implementation of a 'core
      medicines list'.
AB  - During the terminal phase, access to medicines is critical for people wishing to
      spend their last days of life at home. Yet, access to medicines can be
      problematic. The aim of this study was to report the perspectives of specialist
      and generalist health professionals (HPs) on the issues of community access to
      medicines for this vulnerable group. A qualitative descriptive study design
      investigated the views of HPs working in palliative care roles in South
      Australia. Nurses, doctors and pharmacists described their experiences of
      accessing medicines for management of terminal phase symptoms during semi
      structured focus group discussions. Content analysis identified six themes
      including: 'Medication Supply', 'Education and Training', 'Caregiver Burden',
      'Safety', 'Funding' and 'Clinical Governance'. Future projects should aim to
      address these themes when developing strategies for the management of people
      wishing to die at home.

PMID- 28490413
TI  - Risk factors for appendiceal involvement in women with epithelial ovarian cancer.
AB  - OBJECTIVE: To evaluate the risk factors for appendiceal involvement in women with
      epithelial ovarian cancer (EOC) who underwent appendectomy at the time of initial
      surgery. MATERIAL AND METHODS: Patients with a final diagnosis of EOC who
      underwent appendectomy at the time of initial surgery were evaluated
      retrospectively. Risk factors related to the presence of appendiceal involvement
      were analyzed. RESULTS: A total of 210 patients underwent appendectomy during
      staging surgery. Appendiceal involvement was detected in 61 patients. No women
      with apparent clinical early-stage tumors had evidence of isolated metastatic
      disease to the appendix; therefore, no upstaging was detected due to solitary
      appendiceal involvement in this group of patients. For all patients, univariate
      analysis of the appendiceal involvement revealed age, stage, grade, extragenital
      organ involvement (omentum, bowel, peritoneum), positive cytology, and lymph node
      metastasis as significant factors (p<0.05). In the multivariate analysis,
      appendiceal involvement was significantly affected by age and omental
      involvement. Older age (>50 years) [odds ratio (OR) 2.8; 95% confidence interval
      (CI): (1.24-6.37); p=0.014] and presence of omental involvement [OR: 3.2; 95% CI:
      (1.22-8.59); p=0.018) seemed to be independent risk factors for appendiceal
      involvement in women with EOC. CONCLUSION: Our findings indicate that routine
      appendectomy at the time of surgery for apparent early-stage EOC is not
      warranted. Nevertheless, the surgeon can take the initiative in regards to
      performing appendectomy because the morbidity rates due to this procedure are
      negligible. Older age (>50 years) and presence of omental involvement seem to
      increase the risk of appendiceal involvement by 2.8 and 3.2 times, respectively.

PMID- 28490414
TI  - What is your diagnosis?

PMID- 28490415
TI  - Maternal and perinatal characteristics of small-for-gestational-age newborns: Ten
      year experience of a single center.
AB  - OBJECTIVE: To analyze the maternal and perinatal characteristics of small-for
      gestational-age (SGA) newborns compared with appropriate-for-gestational-age
      (AGA) newborns in singleton pregnancies managed at our hospital between January
      2006 and December 2015. MATERIAL AND METHODS: The study (n=456) and control
      (n=4925) groups included pregnancies resulting in SGA and AGA newborns,
      respectively. Additionally, two SGA subgroups were defined according to abnormal
      (n=34) and normal (n=57) Doppler findings. Maternal demographic features;
      intracytoplasmic sperm injection (ICSI) pregnancies; gestational age at delivery;
      birth weight; major congenital anomalies, karyotype abnormalities, and genetic
      syndromes; maternal and obstetric problems such as hypertensive disorders,
      diabetes, oligohydramnios, preterm birth; admission to the neonatal intensive
      care unit (NICU), and perinatal mortality were recorded, and the two groups were
      compared with respect to these parameters. RESULTS: Mean maternal age, parity,
      gestational age at delivery, and birthweight were significantly lower; the
      frequencies of ICSI pregnancies, hypertensive disorders, oligohydramnios, preterm
      delivery, major congenital anomalies, karyotype abnormalities and genetic
      syndromes, admission to the NICU and perinatal mortality were significantly
      higher in the study group (p<0.05). None of the study parameters were
      significantly different between the two SGA subgroups (p>0.05). CONCLUSION: The
      association of SGA with ICSI pregnancies, hypertensive disorders,
      oligohydramnios, preterm delivery, congenital/chromosomal anomalies, NICU
      admission and perinatal mortality may be important in perinatal care. Clinical
      suspicion of SGA necessitates appropriate monitorization and management. Although
      obstetric outcomes were not significantly different between the two SGA subgroups
      with abnormal and normal Doppler findings in this study, this finding must be
      evaluated with caution due to the small sizes.

PMID- 28490416
TI  - Development and Assessment of an E-learning Course on Pediatric Cardiology
      Basics.
AB  - BACKGROUND: Early detection of congenital heart disease is a worldwide problem.
      This is more critical in developing countries, where shortage of professional
      specialists and structural health care problems are a constant. E-learning has
      the potential to improve capacity, by overcoming distance barriers and by its
      ability to adapt to the reduced time of health professionals. OBJECTIVE: The
      study aimed to develop an e-learning pediatric cardiology basics course and
      evaluate its pedagogical impact and user satisfaction. METHODS: The sample
      consisted of 62 health professionals, including doctors, nurses, and medical
      students, from 20 hospitals linked via a telemedicine network in Northeast
      Brazil. The course was developed using Moodle (Modular Object Oriented Dynamic
      Learning Environment; Moodle Pty Ltd, Perth, Australia) and contents adapted from
      a book on this topic. Pedagogical impact evaluation used a pre and posttest
      approach. User satisfaction was evaluated using Wang's questionnaire. RESULTS:
      Pedagogical impact results revealed differences in knowledge assessment before
      and after the course (Z=-4.788; P<.001). Questionnaire results indicated high
      satisfaction values (Mean=87%; SD=12%; minimum=67%; maximum=100%). Course
      adherence was high (79%); however, the withdrawal exhibited a value of 39%, with
      the highest rate in the early chapters. Knowledge gain revealed significant
      differences according to the profession (X22=8.6; P=.01) and specialty (X22=8.4;
      P=.04). Time dedication to the course was significantly different between
      specialties (X22=8.2; P=.04). CONCLUSIONS: The main contributions of this study
      are the creation of an asynchronous e-learning course on Moodle and the
      evaluation of its impact, confirming that e-learning is a viable tool to improve
      training in neonatal congenital heart diseases.

PMID- 28490417
TI  - Accelerating Digital Mental Health Research From Early Design and Creation to
      Successful Implementation and Sustainment.
AB  - Mental health problems are common and pose a tremendous societal burden in terms
      of cost, morbidity, quality of life, and mortality. The great majority of people
      experience barriers that prevent access to treatment, aggravated by a lack of
      mental health specialists. Digital mental health is potentially useful in meeting
      the treatment needs of large numbers of people. A growing number of efficacy
      trials have shown strong outcomes for digital mental health treatments. Yet
      despite their positive findings, there are very few examples of successful
      implementations and many failures. Although the research-to-practice gap is not
      unique to digital mental health, the inclusion of technology poses unique
      challenges. We outline some of the reasons for this gap and propose a collection
      of methods that can result in sustainable digital mental health interventions.
      These methods draw from human-computer interaction and implementation science and
      are integrated into an Accelerated Creation-to-Sustainment (ACTS) model. The ACTS
      model uses an iterative process that includes 2 basic functions (design and
      evaluate) across 3 general phases (Create, Trial, and Sustain). The ultimate goal
      in using the ACTS model is to produce a functioning technology-enabled service
      (TES) that is sustainable in a real-world treatment setting. We emphasize the
      importance of the service component because evidence from both research and
      practice has suggested that human touch is a critical ingredient in the most
      efficacious and used digital mental health treatments. The Create phase results
      in at least a minimally viable TES and an implementation blueprint. The Trial
      phase requires evaluation of both effectiveness and implementation while allowing
      optimization and continuous quality improvement of the TES and implementation
      plan. Finally, the Sustainment phase involves the withdrawal of research or donor
      support, while leaving a functioning, continuously improving TES in place. The
      ACTS model is a step toward bringing implementation and sustainment into the
      design and evaluation of TESs, public health into clinical research, research
      into clinics, and treatment into the lives of our patients.

PMID- 28490418
TI  - Identifying and Understanding the Health Information Experiences and Preferences
      of Caregivers of Individuals With Either Traumatic Brain Injury, Spinal Cord
      Injury, or Burn Injury: A Qualitative Investigation.
AB  - BACKGROUND: In order to meet the challenges of caring for an injured person,
      caregivers need access to health information. However, caregivers often feel that
      they lack adequate information. Previous studies of caregivers have primarily
      focused on either their time and emotional burdens or their health outcomes, but
      the information needs of caregivers have not been thoroughly investigated.
      OBJECTIVE: The purpose of this investigation was to identify the preferred
      sources of health information for caregivers supporting individuals with injuries
      and to explore how access to this information could be improved. METHODS: A total
      of 32 caregivers participated in semistructured interviews, which were used in
      order to develop a more in-depth understanding of these caregivers' information
      needs. Digital audio recordings of the interviews were used for analysis
      purposes. These audio recordings were analyzed using a thematic analysis or
      qualitative content analysis. All of participant's interviews were then coded
      using the qualitative analysis program, Nvivo 10 for Mac (QSR International).
      RESULTS: The caregivers endorsed similar behaviors and preferences when seeking
      and accessing health information. Medical professionals were the preferred source
      of information, while ease of access made the Internet the most common avenue to
      obtain information. The challenges faced by participants were frequently a result
      of limited support. In describing an ideal health system, participants expressed
      interest in a comprehensive care website offering support network resources,
      instructive services about the injury and caregiving, and injury-specific
      materials. CONCLUSIONS: According to the participants, an ideal health
      information system would include a comprehensive care website that offered
      supportive network resources, instructive services about the injury and
      caregiving, and materials specific to the type of patient injury.

PMID- 28490419
TI  - Development, Usability, and Efficacy of a Serious Game to Help Patients Learn
      About Pain Management After Surgery: An Evaluation Study.
AB  - BACKGROUND: Postoperative pain is a persistent problem after surgery and can
      delay recovery and develop into chronic pain. Better patient education has been
      proposed to improve pain management of patients. Serious games have not been
      previously developed to help patients to learn how to manage their postoperative
      pain. OBJECTIVE: The aim of this study was to describe the development of a
      computer-based game for surgical patients to learn about postoperative pain
      management and to evaluate the usability, user experience, and efficacy of the
      game. METHODS: A computer game was developed by an interdisciplinary team
      following a structured approach. The usability, user experience, and efficacy of
      the game were evaluated using self-reported questionnaires (AttrakDiff2,
      Postoperative Pain Management Game Survey, Patient Knowledge About Postoperative
      Pain Management questionnaire), semi-structured interviews, and direct
      observation in one session with 20 participants recruited from the general public
      via Facebook (mean age 48 [SD 14]; 11 women). Adjusted Barriers Questionnaire II
      and 3 questions on health literacy were used to collect background information.
      RESULTS: Theories of self-care and adult learning, evidence for the educational
      needs of patients about pain management, and principles of gamification were used
      to develop the computer game. Ease of use and usefulness received a median score
      between 2.00 (IQR 1.00) and 5.00 (IQR 2.00) (possible scores 0-5; IQR,
      interquartile range), and ease of use was further confirmed by observation.
      Participants expressed satisfaction with this novel method of learning, despite
      some technological challenges. The attributes of the game, measured with
      AttrakDiff2, received a median score above 0 in all dimensions; highest for
      attraction (median 1.43, IQR 0.93) followed by pragmatic quality (median 1.31,
      IQR 1.04), hedonic quality interaction (median 1.00, IQR 1.04), and hedonic
      quality stimulation (median 0.57, IQR 0.68). Knowledge of pain medication and
      pain management strategies improved after playing the game (P=.001). CONCLUSIONS:
      A computer game can be an efficient method of learning about pain management; it
      has the potential to improve knowledge and is appreciated by users. To assess the
      game's usability and efficacy in the context of preparation for surgery, an
      evaluation with a larger sample, including surgical patients and older people, is
      required.

PMID- 28490420
TI  - Testing the Effectiveness of a Primary Care Intervention to Improve Uptake of
      Colorectal Cancer Screening: A Randomized Controlled Trial Protocol.
AB  - BACKGROUND: Screening for colorectal cancer (CRC) significantly reduces mortality
      associated with this disease. In Australia, the National Bowel Cancer Screening
      Program provides regular fecal occult blood tests (FOBT) for those aged 50 to 74
      years, however, participation rates in the program have plateaued at 36%. Given
      low uptake in the National Bowel Cancer Screening Program, it is necessary to
      explore alternate methods to increase CRC screening rates. Primary care is a
      promising adjunct setting to test methods to increase CRC screening
      participation. Primary care guidelines support the recommendation and provision
      of CRC screening to primary care patients. Those in the National Bowel Cancer
      Screening Program target age range frequently present to their primary care
      provider. OBJECTIVE: This study tests the effect that a multicomponent primary
      care-based intervention has on CRC screening uptake when compared to usual care.
      METHODS: Primary care patients presenting for an appointment with their primary
      care provider complete a touchscreen survey to determine eligibility for the
      trial. Those aged 50 to 74 years, at average risk of CRC, with no history of CRC
      or inflammatory bowel disease, who have not had an FOBT in the past 2 years or a
      colonoscopy in the past 5 years are eligible to participate in the trial. Trial
      participants are randomized to the intervention or usual care group by day of
      attendance at the practice. The intervention consists of provision of an FOBT,
      printed information sheet, and primary care provider endorsement to complete the
      FOBT. The usual care group receives no additional care. RESULTS: The primary
      outcome is completion of CRC screening 6 weeks after recruitment. The proportion
      of patients completing CRC screening will be compared between trial groups using
      a logistic regression model. CONCLUSIONS: CRC screening rates in Australia are
      suboptimal and interventions to increase screening participation are urgently
      required. This protocol describes the process of implementing a multicomponent
      intervention designed to increase CRC screening uptake in a primary care setting.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12616001299493;
      https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371136&isReview=true
      (Archived by WebCite at http://www.webcitation.org/6pL0VYIj6). Universal Trial
      Number U1111-1185-6120.

PMID- 28490421
TI  - PatientVOICE: Development of a Preparatory, Pre-Chemotherapy Online Communication
      Tool for Older Patients With Cancer.
AB  - BACKGROUND: Good communication around cancer treatment is essential in helping
      patients cope with their disease and related care, especially when this
      information is tailored to one's needs. Despite its importance, communication is
      often complex, in particular in older patients (aged 65 years or older). In
      addition to the age-related deterioration in information and memory processing
      older patients experience, communication is also complicated by their required
      yet often unmet role of being an active, participatory patient. Older patients
      rarely express their informational needs and their contributions to consultations
      are often limited. Therefore, older patients with cancer need to be prepared to
      participate more actively in their care and treatment. OBJECTIVE: The objective
      of this paper was to report the development of PatientVOICE, an online,
      preparatory tool with audio facility aimed to enhance the participation of older
      patients during educational nursing encounters preceding chemotherapy and to
      improve their information recall. METHODS: PatientVOICE was developed by applying
      the following 6 steps of the intervention mapping framework that involved both
      patients and nurses: (1) needs assessment, (2) specifying determinants and change
      objectives, (3) reviewing and selecting theoretical methods and practical
      strategies, (4) developing intervention components, (5) designing adoption and
      implementation, and (6) making an evaluation plan. RESULTS: A careful execution
      of these consecutive steps resulted in the ready-to-use preparatory website.
      PatientVOICE provides pre-visit information about chemotherapy (ie, medical
      information, side effects, and recommendations of dealing with side effects),
      information about the educational nursing visit preceding chemotherapy (ie, aim,
      structure, and recommendations for preparation), techniques to improve patients'
      communication skills using a question prompt sheet (QPS) and video-modeling
      examples showing "best practices", and the opportunity to upload and listen back
      to an audio recording of a patient's own nursing visit. CONCLUSIONS: The
      development process resulted in PatientVOICE, a multi-component online
      intervention targeted to older patients with cancer. PatientVOICE contains
      information about the treatment as well as information about the role of the
      patient during treatment. Using different methods (QPS and audio facility), we
      hope to support these patients during their treatment. In the future, the utility
      and usability of this complex intervention will be evaluated in a group of older
      patients who receive or have received chemotherapy.

PMID- 28490422
TI  - CFTR-mediated anion secretion across intestinal epithelium-like Caco-2 monolayer
      under PTH stimulation is dependent on intermediate conductance K+ channels.
AB  - Parathyroid hormone (PTH), a pleiotropic hormone that maintains mineral
      homeostasis, is also essential for controlling pH balance and ion transport
      across renal and intestinal epithelia. Optimization of luminal pH is important
      for absorption of trace elements, e.g., calcium and phosphorus. We have
      previously demonstrated that PTH rapidly stimulated electrogenic [Formula: see
      text] secretion in intestinal epithelial-like Caco-2 monolayers, but the
      underlying cellular mechanism, contributions of other ions, particularly Cl- and
      K+, and long-lasting responses are not completely understood. Herein, PTH and
      forskolin were confirmed to induce anion secretion, which peaked within 1-3 min
      (early phase), followed by an abrupt decay and plateau that lasted for 60 min
      (late phase). In both early and late phases, apical membrane capacitance was
      increased with a decrease in basolateral capacitance after PTH or forskolin
      exposure. PTH also induced a transient increase in apical conductance with a long
      lasting decrease in basolateral conductance. Anion secretion in both phases was
      reduced under [Formula: see text]-free and/or Cl--free conditions or after
      exposure to carbonic anhydrase inhibitor (acetazolamide), CFTR inhibitor (CFTRinh
      172), Na+/H+ exchanger (NHE)-3 inhibitor (tenapanor), or K+ channel inhibitors
      (BaCl2, clotrimazole, and TRAM-34; basolateral side), the latter of which
      suggested that PTH action was dependent on basolateral K+ recycling. Furthermore,
      early- and late-phase responses to PTH were diminished by inhibitors of PI3K
      (wortmannin and LY-294002) and PKA (PKI 14-22). In conclusion, PTH requires NHE3
      and basolateral K+ channels to induce [Formula: see text] and Cl- secretion, thus
      explaining how PTH regulated luminal pH balance and pH-dependent absorption of
      trace minerals.

PMID- 28490423
TI  - Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2
      Diabetes: The Hong Kong Diabetes Database.
AB  - OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not
      available in Asia. We examined changes in risk factor control and incidence of
      complications from diabetes and death in a large longitudinal cohort of Chinese
      adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1
      January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes
      underwent metabolic and complication assessment in 16 diabetes centers operated
      by Hong Kong Hospital Authority that provided care to a large majority of
      diagnosed patients. Patients were followed for incident acute myocardial
      infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31
      December 2012. Risk factor levels between enrollment periods were compared.
      Incidence of clinical events, stratified by diabetes duration, was examined over
      time. RESULTS: Incidence of complications from diabetes and death declined over
      the observation period in patients at varying disease duration. Among the high
      risk group with diabetes for at least 15 years, crude incidence of AMI decreased
      from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from
      29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to
      2012. Improvements in levels of metabolic risk factors were detected. Proportion
      of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%,
      blood pressure <=130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L
      from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes
      Database, we observed decreases in incidence of cardiovascular-renal
      complications and death and corresponding improvements in risk factor control
      over a 13-year period.

PMID- 28490425
TI  - Sixty seconds on . . . #publicduty.

PMID- 28490426
TI  - Health care needs and use of health care services among newly arrived Syrian
      refugees: a cross-sectional study.
AB  - BACKGROUND: Canada welcomed 33 723 Syrian refugees between November 2015 and
      November 2016. This paper reports the results of a rapid assessment of health
      care needs and use of health care services among newly arrived Syrian refugees in
      Toronto. METHODS: A cross-sectional study was conducted in Toronto among Syrian
      refugees aged 18 years or more who had been in Canada for 12 months or less.
      Participants were recruited initially through distribution of flyers in hotels
      and through direct referrals and communication with community and settlement
      agency partners, and then through snowball sampling. We collected
      sociodemographic information and data on self-perceived physical health and
      mental health, unmet health care needs and use of health care services. RESULTS:
      A total of 400 Syrian refugees (221 women [55.2%] and 179 men [44.8%]) were
      enrolled. Of the 400, 209 (52.2%) were privately sponsored refugees, 177 (44.2%)
      were government-assisted refugees, and 12 (3.0%) were refugees under the Blended
      Visa Office-Referred Program. They reported high levels of self-perceived
      physical and mental health. Over 90% of the sample saw a doctor in their first
      year in Canada, and 79.8% had a family doctor they saw regularly. However, almost
      half (49.0%) of the respondents reported unmet health care needs, with the 3 most
      common reasons reported being long wait times, costs associated with services and
      lack of time to seek health care services. INTERPRETATION: Many factors may
      explain our respondents' high levels of self-perceived physical and mental health
      during the first year of resettlement, including initial resettlement support and
      eligibility for health care under the Interim Federal Health Program. However,
      newly arrived Syrian refugees report unmet health care needs, which necessitates
      more comprehensive care and management beyond the initial resettlement support.

PMID- 28490424
TI  - Waning Immunity and Microbial Vaccines-Workshop of the National Institute of
      Allergy and Infectious Diseases.
AB  - Since the middle of the 20th century, vaccines have made a significant public
      health impact by controlling infectious diseases globally. Although long-term
      protection has been achieved with some vaccines, immunity wanes over time with
      others, resulting in outbreaks or epidemics of infectious diseases. Long-term
      protection against infectious agents that have a complex life cycle and antigenic
      variation remains a key challenge. Novel strategies to characterize the short-
      and long-term immune responses to vaccines and to induce immune responses that
      mimic natural infection have recently emerged. New technologies and approaches in
      vaccinology, such as adjuvants, delivery systems, and antigen formulations, have
      the potential to elicit more durable protection and fewer adverse reactions;
      together with in vitro systems, these technologies have the capacity to model and
      accelerate vaccine development. The National Institute of Allergy and Infectious
      Diseases (NIAID) held a workshop on 19 September 2016 that focused on waning
      immunity to selected vaccines (for Bordetella pertussis, Salmonella enterica
      serovar Typhi, Neisseria meningitidis, influenza, mumps, and malaria), with an
      emphasis on identifying knowledge gaps, future research needs, and how this
      information can inform development of more effective vaccines for infectious
      diseases.

PMID- 28490427
TI  - Effect of acute intraocular pressure elevation on the minimum rim width in
      normal, ocular hypertensive and glaucoma eyes.
AB  - BACKGROUND: To estimate and compare changes in the Bruch's membrane opening
      minimum rim width (BMO-MRW) and area in normal, ocular hypertensive and glaucoma
      eyes following acute elevations in intraocular pressure (IOP). METHODS: The optic
      nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and
      53 with primary glaucoma) were imaged using Spectral-domain optical coherence
      tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised
      twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an
      ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured
      with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and
      ONH was rescanned with OCT. In each OCT volume, BMO-MRW and area were calculated
      and at each IOP increment. RESULTS: The baseline MRW was significantly smaller in
      glaucoma subjects (174.3+/-54.3 um) compared with normal (287.4+/-42.2 um,
      p<0.001) and OHT subjects (255.4+/-45.3 um, p<0.001). MRW of glaucoma subjects
      was significantly thinner at the first and second IOP elevations than that at
      baseline (both p<0.01), but no significant change was noted in normal and OHT
      subjects. There was no significant change of BMO area at acute IOP elevations
      from baseline in all diagnoses (all p>0.05). CONCLUSION: Acute IOP elevation
      leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma
      subjects only without changing ONH size. This suggests that the neural and
      connective tissues at ONH level in glaucoma subjects are more susceptible to
      acute IOP episodes than OHT or normal controls.

PMID- 28490428
TI  - Famine, conflict, and political indifference.

PMID- 28490429
TI  - Closing the Care Gap: A Primer on Quality Improvement for Heart Failure
      Clinicians.
AB  - Quality improvement (QI) initiatives have become an integral part of patient
      centered care. In this primer, we outline 6 steps for initiating, implementing,
      and monitoring improvement in heart failure care. These steps include
      acknowledging that improvement is needed and setting a culture for improvement;
      forming a QI team; understanding the local problem; generating improvement
      strategies that will fit with the local problem; monitoring; testing; and
      refining improvements, analysis of data, and interpretation of run charts. This
      primer provides tools and resources for clinicians who want to learn how to
      perform QI specifically in the field of heart failure. We will illustrate the
      application of these steps using a hypothetical example for a congestive heart
      failure postdischarge clinic.

PMID- 28490430
TI  - Percutaneous Mitral Valve Edge-to-Edge Repair Assisted by Hemodynamic Support
      Devices: A Case Series of Bailout Procedures.

PMID- 28490431
TI  - Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a
      clinical practice guideline.

PMID- 28490435
TI  - Home Dialysis in the Prospective Payment System Era.
AB  - The ESRD Prospective Payment System introduced two incentives to increase home
      dialysis use: bundling injectable medications into a single payment for treatment
      and paying for home dialysis training. We evaluated the effects of the ESRD
      Prospective Payment System on home dialysis use by patients starting dialysis in
      the United States from January 1, 2006 to August 31, 2013. We analyzed data on
      dialysis modality, insurance type, and comorbidities from the United States Renal
      Data System. We estimated the effect of the policy on home dialysis use with
      multivariable logistic regression and compared the effect on Medicare Parts A/B
      beneficiaries with the effect on patients with other types of insurance. The ESRD
      Prospective Payment System associated with a 5.0% (95% confidence interval [95%
      CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period.
      Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare
      beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other
      forms of health insurance. The difference between these groups was not
      statistically significant (1.8%; 95% CI, -0.2% to 3.8%). Conversely, in both
      populations, the training add-on did not associate with increases in home
      dialysis use beyond the effect of the policy. The ESRD Prospective Payment System
      bundling, but not the training add-on, associated with substantial increases in
      home dialysis, which were identical for both Medicare and non-Medicare patients.
      These spill-over effects suggest that major payment changes in Medicare can
      affect all patients with ESRD.

PMID- 28490433
TI  - Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1beta- and
      IL-6-Related Impairment of Bone Marrow Function.
AB  - RATIONALE: Intracoronary infusion of bone marrow (BM) mononuclear cells after
      acute myocardial infarction (AMI) has led to limited improvement in left
      ventricular function. Although experimental AMI models have implicated cytokine
      related impairment of progenitor cell function, this response has not been
      investigated in humans. OBJECTIVE: To test the hypothesis that peripheral blood
      (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and
      cardiac function after AMI. METHODS AND RESULTS: BM and PB samples were collected
      from 87 participants 14 to 21 days after AMI and BM from healthy donors was used
      as a reference. Correlations between cytokine concentrations and cell phenotypes,
      cell functions, and post-AMI cardiac function were determined. PB interleukin-6
      (IL-6) negatively correlated with endothelial colony-forming cell colony maximum
      in the BM of patients with AMI (estimate+/-SE, -0.13+/-0.05; P=0.007). BM from
      healthy individuals showed a dose-dependent decrease in endothelial colony
      forming cell colony outgrowth in the presence of exogenous IL-1beta or IL-6
      (P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study
      participants, the angiogenic cytokine platelet-derived growth factor BB
      glycoprotein correlated positively with BM-derived colony-forming unit
      endothelial colony maximum (estimate+/-SE, 0.01+/-0.002; P<0.001), multipotent
      mesenchymal stromal cell colony maximum (estimate+/-SE, 0.01+/-0.002; P=0.002) in
      BM, and mesenchymal stromal cell colony maximum in PB (estimate+/-SE, 0.02+/
      0.005; P<0.001). CONCLUSIONS: Two weeks after AMI, increased PB platelet-derived
      growth factor BB glycoprotein was associated with increased BM function, whereas
      increased IL-6 was associated with BM impairment. Validation studies confirmed
      inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R
      or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors
      may improve the regenerative capacity of BM cells after AMI. CLINICAL TRIAL
      REGISTRATIONS: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00684060.

PMID- 28490436
TI  - Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein
      Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: There are inconsistent reports on the association of
      dietary protein intake with serum albumin and outcomes among patients on
      hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable
      accounting for residual renal urea clearance, we hypothesized that higher
      baseline nPCR and rise in nPCR would be associated with higher serum albumin and
      better survival among incident hemodialysis patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Among 36,757 incident hemodialysis patients in a
      large United States dialysis organization, we examined baseline and change in
      renal urea clearance-corrected nPCR as a protein intake surrogate and modeled
      their associations with serum albumin and mortality over 5 years (1/2007
      12/2011). RESULTS: Median nPCRs with and without accounting for renal urea
      clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median
      within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day).
      During a median follow-up period of 1.4 years, 8481 deaths were observed.
      Baseline renal urea clearance-corrected nPCR was associated with higher serum
      albumin and lower mortality in the fully adjusted model (Ptrend<0.001). Among
      13,895 patients with available data, greater rise in renal urea clearance
      corrected nPCR during the first 6 months was also associated with attaining high
      serum albumin (>=3.8 g/dl) and lower mortality (Ptrend<0.001); compared with the
      reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were
      0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval,
      1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day
      and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence
      interval, 0.64 to 0.90), respectively, among those with a change of >=0.5 g/kg
      per day. Within a given category of nPCR without accounting for renal urea
      clearance, higher levels of renal urea clearance-corrected nPCR consistently
      showed lower mortality risk. CONCLUSIONS: Among incident hemodialysis patients,
      higher dietary protein intake represented by nPCR and its changes over time
      appear to be associated with increased serum albumin levels and greater survival.
      nPCR may be underestimated when not accounting for renal urea clearance. Compared
      with the conventional nPCR, renal urea clearance-corrected nPCR may be a better
      marker of mortality.

PMID- 28490437
TI  - High-throughput CRISPRi phenotyping identifies new essential genes in
      Streptococcus pneumoniae.
AB  - Genome-wide screens have discovered a large set of essential genes in the
      opportunistic human pathogen Streptococcus pneumoniae However, the functions of
      many essential genes are still unknown, hampering vaccine development and drug
      discovery. Based on results from transposon sequencing (Tn-seq), we refined the
      list of essential genes in S. pneumoniae serotype 2 strain D39. Next, we created
      a knockdown library targeting 348 potentially essential genes by CRISPR
      interference (CRISPRi) and show a growth phenotype for 254 of them (73%). Using
      high-content microscopy screening, we searched for essential genes of unknown
      function with clear phenotypes in cell morphology upon CRISPRi-based depletion.
      We show that SPD_1416 and SPD_1417 (renamed to MurT and GatD, respectively) are
      essential for peptidoglycan synthesis, and that SPD_1198 and SPD_1197 (renamed to
      TarP and TarQ, respectively) are responsible for the polymerization of teichoic
      acid (TA) precursors. This knowledge enabled us to reconstruct the unique
      pneumococcal TA biosynthetic pathway. CRISPRi was also employed to unravel the
      role of the essential Clp-proteolytic system in regulation of competence
      development, and we show that ClpX is the essential ATPase responsible for ClpP
      dependent repression of competence. The CRISPRi library provides a valuable tool
      for characterization of pneumococcal genes and pathways and revealed several
      promising antibiotic targets.

PMID- 28490439
TI  - Skeletal muscle metabolism during prolonged exercise in Pompe disease.
AB  - OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha
      glucosidase deficiency, which leads to a block in intra-lysosomal glycogen
      breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be
      a progressive metabolic myopathy. Considering the health benefits of exercise, it
      is important in Pompe disease to acquire more information about muscle substrate
      use during exercise. METHODS: Seven adults with Pompe disease were matched to a
      healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak)
      and (2) carbohydrate and fatty acid metabolism during submaximal exercise (33 W)
      for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable
      isotopes. RESULTS: In the patients, VO2peak was less than half of average control
      values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the
      respiratory exchange ratio increased to >1.0 and lactate levels rose 5-fold in
      the patients, indicating significant glycolytic flux. In line with this, during
      submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate
      were similar between patients and controls (mean difference 0.226 g/min (CI:
      0.611 to -0.078, P = 0.318) and mean difference 0.016 umol/kg/min (CI: 1.287 to 
      1.255, P = 0.710), respectively). CONCLUSION: Reflecting muscle weakness and
      wasting, Pompe disease is associated with markedly reduced maximal exercise
      capacity. However, glycogenolysis is not impaired in exercise. Unlike in other
      metabolic myopathies, skeletal muscle substrate use during exercise is normal in
      Pompe disease rendering exercise less complicated for e.g. medical or
      recreational purposes.

PMID- 28490438
TI  - Inefficient recruitment of kinesin-1 to melanosomes precludes it from
      facilitating their transport.
AB  - Microtubules and F-actin, and their associated motor proteins, are considered to
      play complementary roles in long- and short-range organelle transport. However,
      there is growing appreciation that myosin/F-actin networks can drive long-range
      transport. In melanocytes, myosin-Va and kinesin-1 have both been proposed as
      long-range centrifugal transporters moving melanosomes into the peripheral
      dendrites. Here, we investigated the role of kinesin-1 heavy chain (Kif5b) and
      its suggested targeting factor Rab1a in transport. We performed confocal
      microscopy and subcellular fractionation, but did not detect Kif5b or Rab1a on
      melanosomes. Meanwhile functional studies, using siRNA knockdown and dominant
      negative mutants, did not support a role for Kif5b or Rab1a in melanosome
      transport. To probe the potential of Kif5b to function in transport, we generated
      fusion proteins that target active Kif5b to melanosomes and tested their ability
      to rescue perinuclear clustering in myosin-Va-deficient cells. Expression of
      these chimeras, but not full-length Kif5b, dispersed melanosomes with similar
      efficiency to myosin-Va. Our data indicate that kinesin and microtubules can
      compensate for defects in myosin-Va and actin-based transport in mammals, but
      that endogenous Kif5b does not have an important role in transport of melanocytes
      due to its inefficient recruitment to melanosomes.

PMID- 28490442
TI  - Dexamethasone and sex regulate placental glucocorticoid receptor isoforms in
      mice.
AB  - Maternal dexamethasone exposure in the mouse impairs placental development and
      programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to
      different glucocorticoid receptor (GR) isoforms to regulate gene transcription
      and cellular signaling. We hypothesized that sexually dimorphic placental
      responses to glucocorticoids are due to differences in GR isoforms present in the
      placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5
      until E14.5 (1 ug/kg/h) before the collection of placentae. Cytoplasmic and
      nuclear protein fractions were extracted from placentae of male and female
      fetuses for Western blot analysis of GR isoforms. Eight known isoforms of the GR
      were detected in the mouse placenta including the translational isoforms GRalpha
      A, B, C and D1-3 and the splice variants GRA and GRP. The expression of GRA, GRP
      and each of the GRalpha isoforms were altered by dexamethasone in relation to
      fetal sex and cellular location. Placentae of female fetuses had higher GRalpha-A
      and GRP expression in the cytoplasm than males, and GRalpha-C was more highly
      expressed in the nucleus of females than that in males. Dexamethasone
      significantly increased the cytoplasmic expression of GRalpha-A, but reduced the
      expression of GRalpha-C in placentae of males. Dexamethasone increased the
      expression of the GRalpha-C-regulated genes Sgk1 and Bcl2l11, particularly in
      females. The cleaved caspase-3 staining in placental sections indicated GRalpha-C
      may mediate sex differences in dexamethasone-induced apoptosis. These findings
      may underlie the sex-specific placental adaptations that regulate different
      growth profiles in males and females and different risks for programmed disease
      outcomes in offspring.

PMID- 28490440
TI  - Human memory CD8 T cell effector potential is epigenetically preserved during in
      vivo homeostasis.
AB  - Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining
      long-lived T cell-mediated immunity. In this study, we report that maintenance of
      human memory CD8 T cell effector potential during in vitro and in vivo
      homeostatic proliferation is coupled to preservation of acquired DNA methylation
      programs. Whole-genome bisulfite sequencing of primary human naive, short-lived
      effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory
      (TSCM) CD8 T cells identified effector molecules with demethylated promoters and
      poised for expression. Effector-loci demethylation was heritably preserved during
      IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven
      proliferation of TCM and TSCM memory cells resulted in phenotypic conversion into
      TEM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci.
      Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo
      proliferation in lymphodepleted recipients also maintained their effector
      associated demethylated status but acquired TEM-associated programs. These data
      demonstrate that effector-associated epigenetic programs are preserved during
      cytokine-driven subset interconversion of human memory CD8 T cells.

PMID- 28490441
TI  - PD-1 regulates KLRG1+ group 2 innate lymphoid cells.
AB  - Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and
      maintain tissue homeostasis in response to cytokines. Positive regulation of ILC
      2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an
      important negative regulator of KLRG1+ ILC-2 function in both mice and humans.
      Increase in KLRG1+ ILC-2 cell numbers was attributed to an intrinsic defect in PD
      1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus
      brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred
      in Pdcd1-/- mice and, upon adoptive transfer, Pdcd1-/- KLRG1+ ILC-2s
      significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody
      increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore, PD-1 is
      required for maintaining the number, and hence function, of KLRG1+ ILC-2s.

PMID- 28490443
TI  - Peripheral insulin resistance in ILK-depleted mice by reduction of GLUT4
      expression.
AB  - The development of insulin resistance is characterized by the impairment of
      glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix
      changes are induced when the metabolic dysregulation is sustained. The present
      work was devoted to analyze the possible link between the extracellular-to
      intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue
      modification that leads to glucose homeostasis impairment. Mice with general
      depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited
      increased glycemia and insulinemia concurrently with a reduction of the
      expression and membrane presence of GLUT4 in the insulin-sensitive peripheral
      tissues compared with their wild-type littermates (WT). Tolerance tests and
      insulin sensitivity indexes confirmed the insulin resistance in cKD-ILK,
      suggesting a similar stage to prediabetes in humans. Under randomly fed
      conditions, no differences between cKD-ILK and WT were observed in the expression
      of insulin receptor (IR-B) and its substrate IRS-1 expressions. The IR-B isoform
      phosphorylated at tyrosines 1150/1151 was increased, but the AKT phosphorylation
      in serine 473 was reduced in cKD-ILK tissues. Similarly, ILK-blocked myotubes
      reduced their GLUT4 promoter activity and GLUT4 expression levels. On the other
      hand, the glucose uptake capacity in response to exogenous insulin was impaired
      when ILK was blocked in vivo and in vitro, although IR/IRS/AKT phosphorylation
      states were increased but not different between groups. We conclude that ILK
      depletion modifies the transcription of GLUT4, which results in reduced
      peripheral insulin sensitivity and glucose uptake, suggesting ILK as a molecular
      target and a prognostic biomarker of insulin resistance.

PMID- 28490444
TI  - Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney
      injury.
AB  - Acute kidney injury (AKI), resulting from chemotherapeutic agents such as
      cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI
      involves apoptotic and necrotic cell death, pathways regulated by sphingolipids
      such as ceramide and glucosylceramide. Results from this study indicate that
      C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide
      levels in the renal cortex 72 h following cisplatin treatment. Pretreatment of
      mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis
      (amitriptyline and myriocin, respectively) prevented accumulation of ceramides
      and hexosylceramide in the renal cortex and protected from cisplatin-induced AKI.
      To determine the role of ceramide metabolism to hexosylceramides in kidney
      injury, we treated mice with a potent and highly specific inhibitor of
      glucosylceramide synthase, the enzyme responsible for catalyzing the
      glycosylation of ceramides to form glucosylceramides. Inhibition of
      glucosylceramide synthase attenuated the accumulation of the hexosylceramides and
      exacerbated ceramide accumulation in the renal cortex following treatment of mice
      with cisplatin. Increasing ceramides and decreasing glucosylceramides in the
      renal cortex sensitized mice to cisplatin-induced AKI according to markers of
      kidney function, kidney injury, inflammation, cell stress, and apoptosis. Under
      conditions of high ceramide generation, data suggest that metabolism of ceramides
      to glucosylceramides buffers kidney ceramides and helps attenuate kidney injury.
      Dupre, T. V., M. A. Doll, P. P. Shah, C. N. Sharp, D. Siow, J. Megyesi, J.
      Shayman, A. Bielawska, J. Bielawski, L. J. Beverly, M. Hernandez-Corbacho, C. J.
      Clarke, A. J. Snider, R. G. Schnellmann, L. M. Obeid, Y. A. Hannun, and L. J.
      Siskind. Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute
      kidney injury. J. Lipid Res 2017. 58: 1439-1452.

PMID- 28490446
TI  - Tolerance to herbivory and the resource availability hypothesis.
AB  - The resource availability hypothesis (RAH), the most successful theory explaining
      plant defence patterns, predicts that defence investment is related to the
      relative growth rate (RGR) of plant species, which is associated with habitat
      quality. Thus, fast-growing species should show lower resistance than slow
      growing species, which would lead fast growers to sustain higher herbivory rates,
      but the fitness consequences of herbivory would be greater for slow growers. The
      latter is often assumed but rarely tested. In a temperate rainforest, we tested
      the expected pattern of tolerance to herbivory derived from the RAH: that fast
      growing species should be more tolerant than slow-growing species. We also
      evaluated whether other plant features covary with RGR (leaf lifespan, shade
      tolerance and leaf toughness) and thus could also contribute to the patterns of
      tolerance to herbivory. As expected, seedlings from tree species with higher RGR
      showed greater tolerance to herbivory. Among the three plant features included,
      only leaf lifespan showed a significant association with RGR, but RGR was the
      best predictor of tolerance. We argue that plant tolerance to herbivory must be
      evaluated to properly verify the assumptions of the RAH.

PMID- 28490445
TI  - Serological Epithelial Component Proteins Identify Intestinal Complications in
      Crohn's Disease.
AB  - Crohn's Disease (CD) is a relapsing inflammation of the gastrointestinal tract
      that affects a young working age population and is increasing in developing
      countries. Half of all sufferers will experience stricturing or fistulizing
      intestinal complications that require extensive surgical interventions and
      neither genes nor clinical risk factors can predict this debilitating natural
      history. We applied discovery and verification phase studies as part of an NCI
      FDA modeled biomarker pipeline to identify differences in the low-mass (<25kDa)
      blood-serum proteome between CD behavioral phenotypes. A significant enrichment
      of epithelial component proteins was identified in CD patients with intestinal
      complications using quantitative proteomic profiling with label-free Liquid
      Chromatography-Tandem Mass Spectrometry (LC-MS/MS). DAVID 6.7 (NIH) was used for
      functional annotation analysis of detected proteins and immunoblotting and
      multiple reaction monitoring (MRM) to verify a priori findings in a secondary
      independent cohort of complicated CD (CCD), uncomplicated inflammatory CD (ICD),
      Th1/17 pathway inflammation controls (rheumatoid arthritis), inflammatory bowel
      disease controls (ulcerative colitis), and healthy controls. Seventy-six high
      confidence serum proteins were modulated in CCD versus ICD by LC-MS/MS (p < 0.05,
      FDR q<0.01), annotating to pathways of epithelial barrier homeostasis (p < 0.01).
      In verification phase, a putative serology panel developed from discovery
      proteomics data consisting of desmoglein-1, desmoplakin, and fatty acid-binding
      protein 5 (FABP5) distinguished CCD from all other groups (p = 0.041) and
      discriminated complication in CD (70% sensitivity and 72.5% specificity at score
      >=1.907, AUC = 0.777, p = 0.007). An MRM assay secondarily confirmed increased
      FABP5 levels in CCD (p < 0.001). In a longitudinal subanalysis-cohort, FABP5
      levels were stable over a two-month period with no behavioral changes (p =
      0.099). These studies along the biomarker development pipeline provide
      substantial proof-of-principle that a blood test can be developed specific to
      transmural intestinal injury. Data are available via the PRIDE proteomics data
      repository under identifier PXD001821 and PeptideAtlas with identifier PASS00661.

PMID- 28490447
TI  - Plant spines deter herbivory by restricting caterpillar movement.
AB  - The spines of flowering plants are thought to function primarily in defence
      against mammalian herbivores; however, we previously reported that feeding by
      Manduca sexta caterpillars on the leaves of horsenettle plants (Solanum
      carolinense) induces increased development of internode spines on new growth. To
      determine whether and how spines impact caterpillar feeding, we conducted assays
      with three Solanaceous plant species that vary in spine numbers (S. carolinense,
      S. atropurpureum and S. aethiopicum) and also manipulated spine numbers within
      each species. We found that M. sexta caterpillars located experimentally isolated
      target leaves much more quickly on plants with experimentally removed spines
      compared with plants with intact spines. Moreover, it took caterpillars longer to
      defoliate species with relatively high spine numbers (S. carolinense and
      particularly Satropurpureum) compared with S. aethiopicum, which has fewer
      spines. These findings suggest that spines may play a significant role in defence
      against insect herbivores by restricting herbivore movement and increasing the
      time taken to access feeding sites, with possible consequences including longer
      developmental periods and increased vulnerability or apparency to predators.

PMID- 28490448
TI  - Intermittent hypoxia training blunts cerebrocortical presenilin 1 overexpression
      and amyloid-beta accumulation in ethanol-withdrawn rats.
AB  - Abrupt cessation of chronic alcohol consumption triggers signaling cascades that
      harm vulnerable brain regions and produce neurobehavioral deficits. We have
      demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in
      rats prevents brain damage and neurobehavioral impairment resulting from abrupt
      ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated
      protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of gamma
      secretase that produces the neurotoxic amyloid-beta (Abeta) peptides Abeta40 and
      Abeta42. We tested the hypotheses that 1) IHT limits EW-induced activation of the
      p38-PS1 axis, thereby attenuating gamma-secretase activation and Abeta
      accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate,
      molecular chaperone, and antioxidant, and provokes protein carbonylation in a
      manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol
      diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A
      20-day IHT program (5-8 daily cycles of 5-10 min of 9.5-10% fractional inspired
      O2 + 4 min of 21% fractional inspired O2) was administered during the first EW
      phase. After the second EW phase, the brain was excised and the prefrontal cortex
      extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by
      immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein
      carbonyl content by spectrometry, and Abeta40 and Abeta42 contents by enzyme
      linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p
      p38, Abeta40, Abeta42, and protein carbonyl contents, but not that of PS1
      messenger RNA, while preserving functionally competent HSP25 dimers in EW rats.
      Collectively, these findings suggest that IHT may attenuate EW-induced gamma
      secretase overactivation by suppressing activation of the p38-PS1 axis and by
      preventing oxidative protein damage.

PMID- 28490450
TI  - Sedentary conditions and enhanced responses to GABA in the RVLM: role of the
      contralateral RVLM.
AB  - A sedentary lifestyle is a major risk factor for cardiovascular disease, and both
      conditions are associated with overactivity of the sympathetic nervous system.
      Ongoing discharge of sympathetic nerves is regulated by the rostral ventrolateral
      medulla (RVLM), which in turn is modulated by the primary excitatory and
      inhibitory neurotransmitters glutamate and gamma-amino-butyric acid (GABA),
      respectively. We reported previously that sedentary conditions enhance GABAergic
      modulation of sympathoexcitation in the RVLM, despite overall increased
      sympathoexcitation. Thus the purpose of this study was to test the hypothesis
      that sedentary conditions increase responsiveness to GABA in RVLM. Male Sprague
      Dawley rats performed either chronic wheeling running or remained sedentary for
      12-15 wk. Animals were instrumented to perform RVLM microinjections under Inactin
      anesthesia while mean arterial pressure (MAP) and splanchnic sympathetic nerve
      activity (SSNA) were recorded. Unilateral microinjections of GABA (30 nl, 0.3-600
      mM) into the RVLM produced dose-dependent decreases in MAP and SSNA; however, no
      group differences were observed. Inhibition of the contralateral RVLM (muscimol,
      2 mM, 90 nl) caused decreases in MAP and SSNA that were not different between
      groups but enhanced decreases in SSNA to GABA in sedentary rats only. In
      sinoaortic denervated rats, GABA microinjections before or after inhibition of
      the contralateral RVLM caused decreases in MAP and SSNA that were not different
      between groups. Our results suggest that the contralateral RVLM plays an
      important role in buffering responses to inhibition of the ipsilateral RVLM under
      sedentary but not physically active conditions. Based on these studies and
      others, sedentary conditions appear to enhance both sympathoinhibitory and
      sympathoexcitatory mechanisms in the RVLM. Enhanced sympathoinhibition may act to
      reduce already elevated sympathetic nervous system activity following sedentary
      conditions.

PMID- 28490449
TI  - Enhanced insulin secretion and insulin sensitivity in young lambs with placental
      insufficiency-induced intrauterine growth restriction.
AB  - Intrauterine growth restriction (IUGR) is associated with persistent metabolic
      complications, but information is limited for IUGR infants. We determined glucose
      stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with
      placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR (n =
      7) were compared with control lambs (n = 8). GSIS was measured at 8 +/- 1 days of
      age, and at 15 +/- 1 days, body weight-specific glucose utilization rates were
      measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp
      (HEC). IUGR lambs weighed 23% less (P < 0.05) than controls at birth. Fasting
      plasma glucose and insulin concentrations were not different between IUGR and
      controls for either study. First-phase insulin secretion was enhanced 2.3-fold in
      IUGR lambs compared with controls. However, second-phase insulin concentrations,
      glucose-potentiated arginine-stimulated insulin secretion, and beta-cell mass
      were not different, indicating that IUGR beta-cells have an intrinsic enhancement
      in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific
      glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold)
      and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose
      utilization was not due to differences in skeletal muscle insulin receptor and
      glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during
      HEC were elevated in IUGR lambs compared with controls, but no differences were
      found for glycogen content or citrate synthase activity in liver and muscle.
      Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in
      young lambs are predicted from fetal studies but may promote conditions that
      exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants.

PMID- 28490451
TI  - Evidence for intraventricular secretion of angiotensinogen and angiotensin by the
      subfornical organ using transgenic mice.
AB  - Direct intracerebroventricular injection of angiotensin II (ANG II) causes
      increases in blood pressure and salt and water intake, presumably mimicking an
      effect mediated by an endogenous mechanism. The subfornical organ (SFO) is a
      potential source of cerebrospinal fluid (CSF), ANG I, and ANG II, and thus we
      hypothesized that the SFO has a secretory function. Endogenous levels of
      angiotensinogen (AGT) and renin are very low in the brain. We therefore examined
      the immunohistochemical localization of angiotensin peptides and AGT in the SFO,
      and AGT in the CSF in two transgenic models that overexpress either human AGT (A+
      mice), or both human AGT (hAGT) and human renin (SRA mice) in the brain.
      Measurements were made at baseline and following volumetric depletion of CSF.
      Ultrastructural analysis with immunoelectron microscopy revealed that
      superficially located ANG I/ANG II and AGT immunoreactive cells in the SFO were
      vacuolated and opened directly into the ventricle. Withdrawal of CSF produced an
      increase in AGT in the CSF that was accompanied by a large decline in AGT
      immunoreactivity within SFO cells. Our data provide support for the hypothesis
      that the SFO is a secretory organ that releases AGT and possibly ANG I/ANG II
      into the ventricle at least under conditions when genes that control the renin
      angiotensin system are overexpressed in mice.

PMID- 28490453
TI  - Joanna Cannon: Psychiatry and paperbacks.

PMID- 28490452
TI  - Role of endothelial nitric oxide in control of peripheral vascular conductance
      during muscle metaboreflex activation.
AB  - The muscle metaboreflex is a powerful pressor reflex induced by the activation of
      chemically sensitive muscle afferents as a result of metabolite accumulation.
      During submaximal dynamic exercise, the rise in arterial pressure is primarily
      due to increases in cardiac output, since there is little systemic
      vasoconstriction. Indeed, in normal animals, we have often shown a small, but
      significant, peripheral vasodilation during metaboreflex activation, which is
      mediated, at least in part, by release of epinephrine and activation of vascular
      beta2-receptors. We tested whether this vasodilation is in part due to increased
      release of nitric oxide caused by the rise in cardiac output eliciting
      endothelium-dependent flow-mediated vasodilation. The muscle metaboreflex was
      activated via graded reductions in hindlimb blood flow during mild exercise with
      and without nitric oxide synthesis blockade [NG-nitro-l-arginine methyl ester (l
      NAME); 5 mg/kg]. We assessed the role of increased cardiac output in mediating
      peripheral vasodilation via the slope of the relationship between the rise in
      nonischemic vascular conductance (conductance of all vascular beds excluding
      hindlimbs) vs. the rise in cardiac output. l-NAME increased mean arterial
      pressure at rest and during exercise. The metaboreflex-induced increases in mean
      arterial pressure were unaltered by l-NAME, whereas the increases in cardiac
      output and nonischemic vascular conductance were attenuated. However, the slope
      of the relationship between nonischemic vascular conductance and cardiac output
      was not affected by l-NAME, indicating that the rise in cardiac output did not
      elicit vasodilation via increased release of nitric oxide. Thus, although nitric
      oxide is intrinsic to the vascular tonus, endothelial-dependent flow-mediated
      vasodilation plays little role in the small peripheral vasodilation observed
      during muscle metaboreflex activation.

PMID- 28490454
TI  - Dying together.

PMID- 28490456
TI  - Does treadmill running performance, heart rate and breathing rate response during
      maximal graded exercise improve after volitional respiratory muscle training?
AB  - AIM: Maximal physical exertion in sports usually causes fatigue in the exercising
      muscles, but not in the respiratory muscles due to triggering of the Respiratory
      muscle metabo-reflex, a sympathetic vasoconstrictor response leading to
      preferential increment in blood flow to respiratory muscles.1 We planned to
      investigate whether a six week yogic pranayama based Volitional Respiratory
      Muscle Training (VRMT) can improve maximal Graded Exercise Treadmill Test (GXTT)
      performance in healthy adult recreational sportspersons. METHODS: Consecutive,
      consenting healthy adult recreational sportspersons aged 20.56+/-2.49 years
      (n=30), volunteered to 'baseline recording' of resting heart rate (HR), blood
      pressure (BP), respiratory rate (RR), and Bruce ramp protocol maximal GXTT until
      volitional exhaustion providing total test time (TTT), derived VO2max, Metabolic
      Equivalent of Task (METs), HR and BP response during maximal GXTT and drop in
      recovery HR data. After six weeks of observation, they underwent 'pre
      intervention recording' followed by supervised VRMT intervention for 6 weeks (30
      minutes a day; 5 days a week) and then 'post-intervention recording'. Repeated
      measures ANOVA with pairwise t statistical comparison was used to analyse the
      data. RESULTS: After supervised VRMT, we observed significant decrease in their
      resting supine RR (p<0.001), resting supine HR (p=0.001), HR after 5 minutes of
      assuming standing posture (p=0.003); significant increase in TTT (p<0.001),
      derived VO2max (p<0.001), METs (p<0.001) and drop in recovery HR (p=0.038);
      altered HR response and BP response during exercise. CONCLUSIONS: We hypothesize
      that these changes are probably due to VRMT induced learnt behaviour to control
      the breathing pattern that improves breathing economy, improvement in respiratory
      muscle aerobic capacity, attenuation of respiratory muscle metabo-reflex,
      increase in cardiac stroke volume and autonomic resetting towards parasympatho
      dominance. Yogic Pranayama based VRMT can be used in sports conditioning
      programme of athletes to further improve their maximal exercise performance, and
      as part of rehabilitation training during return from injury.

PMID- 28490455
TI  - Speckle tracking echocardiography in acute lupus myocarditis: comparison to
      conventional echocardiography.
AB  - AIMS: Lupus myocarditis occurs in 5-10% of patients with systemic lupus
      erythematosus (SLE). No single feature is diagnostic of lupus myocarditis.
      Speckle tracking echocardiography (STE) can detect subclinical left ventricular
      dysfunction in SLE patients, with limited research on its utility in clinical
      lupus myocarditis. We report on STE in comparison to conventional
      echocardiography in patients with clinical lupus myocarditis. METHODS AND
      RESULTS: A retrospective study was done at a tertiary referral hospital in South
      Africa. SLE patients with lupus myocarditis were included and compared to healthy
      controls. Echocardiographic images were reanalyzed, including global longitudinal
      strain through STE. A poor echocardiographic outcome was defined as final left
      ventricular ejection fraction (LVEF) <40%. 28 SLE patients fulfilled the
      criteria. Global longitudinal strain correlated with global (LVEF: r = -0.808; P
      = 0.001) and regional (wall motion score: r = 0.715; P < 0.001) function. In
      patients presenting with a LVEF >=50%, global longitudinal strain (P = 0.023),
      wall motion score (P = 0.005) and diastolic function (P = 0.004) were
      significantly impaired vs controls. Following treatment, LVEF (35-47% (P =
      0.023)) and wall motion score (1.88-1.5 (P = 0.017)) improved but not global
      longitudinal strain. Initial LVEF (34%; P = 0.046) and global longitudinal strain
      (-9.5%; P = 0.095) were lower in patients with a final LVEF <40%. CONCLUSIONS:
      This is the first known report on STE in a series of patients with clinical lupus
      myocarditis. Global longitudinal strain correlated with regional and global left
      ventricular function. Global longitudinal strain, wall motion score and diastolic
      parameters may be more sensitive markers of lupus myocarditis in patients
      presenting with a preserved LVEF >=50%. A poor initial LVEF and global
      longitudinal strain were associated with a persistent LVEF <40%. Echocardiography
      is a non-invasive tool with diagnostic and prognostic value in lupus myocarditis.

PMID- 28490457
TI  - Prognostic factors for musculoskeletal injury identified through medical
      screening and training load monitoring in professional football (soccer): a
      systematic review.
AB  - OBJECTIVES: To identify prognostic factors and models for spinal and lower
      extremity injuries in adult professional/elite football players from medical
      screening and training load monitoring processes. METHODS: The MEDLINE, AMED,
      EMBASE, CINAHL Plus, SPORTDiscus electronic bibliographic databases and the
      Cochrane Database of Systematic Reviews were searched from inception to July
      2016. Searches were limited to original research, published in peer reviewed
      journals of any language. The Quality in Prognostic Studies (QUIPS) tool was used
      for appraisal and the modified GRADE approach was used for synthesis. Prospective
      and retrospective cohort study designs of spinal and lower extremity injury
      incidence were found from populations of adult professional/elite football
      players, between 16 and 40 years. Non-football or mixed sports were excluded.
      RESULTS: 858 manuscripts were identified. Removing duplications left 551 studies,
      which were screened for eligibility by title and abstract. Of these, 531 studies
      were not eligible and were excluded. The full text of the remaining 20 studies
      were obtained; a further 10 studies were excluded. 10 studies were included for
      appraisal and analysis, for 3344 participants. CONCLUSIONS: Due to the paucity
      and heterogeneity of the literature, and shortcomings in methodology and
      reporting, the evidence is of very low or low quality and therefore cannot be
      deemed robust enough to suggest conclusive prognostic factors for all lower limb
      musculoskeletal injury outcomes identified. No studies were identified that
      examined spinal injury outcomes or prognostic models.

PMID- 28490458
TI  - Subcategories of tendinopathy using ultrasound tissue characterization (utc):
      dorsal mid-portion achilles tendinopathy is more severe than ventral achilles
      tendinopathy.
AB  - AIM: To evaluate the association between tendon structure and clinical severity.
      Looking specifically at location of pathology, comparing ventral versus dorsal
      tendinopathy. METHODS: Patients were recruited from a tertiary tendinopathy
      center between Jan 2015 - June 2016. Inclusion criteria included patients with
      midportion Achilles tendinopathy, aged between 1870. Patients with insertional
      Achilles tendinopathy or other suspected etiology were excluded. Patients were
      assessed using ultrasound tissue characterization (UTC) scanning. UTC software
      was used to analyse a 2 cm block 24 cm from the calcaneum for percentage of echo
      type I, II, III and IV. With percentage echo type I+II used as the primary
      outcome. A doctor also categorised patients into predominately dorsal or ventral
      pathology based on UTC imaging. VISAA and VAS scores were used for clinical
      outcome measures. Statistics were undertaken using SPSS, data was not normally
      distributed RESULTS: Overall 33 tendons with mid portion Achilles tendinopathy
      were analysed, the overall percentage echo type I+II showed no correlation to
      either VISAA (p=0.745, r=0.0600) or VAS (p=0.157, r=0.248). When divided into
      dorsal and ventral Achilles tendinopathy there was a significant difference
      between baseline VISAA scores with a lower VISAA score 35 (SD+/-19) in dorsal
      group compared with the ventral group 60 (SD+/-17.1) (p=0.009). There was also a
      higher VAS score in the dorsal group (mean = 6, SD+/-2.28) at baseline compared
      with ventral (mean = 5, SD+/-3.07), although this was not significant (p=0.416).
      CONCLUSIONS: This highlights the possibility of using UTC to subcategories
      patients into ventral and dorsal which seems to correlate to increased clinical
      severity in the dorsal group. This is perhaps due to increased tension and
      stretching acting through this part of the tendon on loading and thus more
      nociceptive stimulation and greater dysfunction of the tendon. This could be used
      to help determine differing rehabilitation interventions in future with differing
      intensities for the two groups. It further highlights as previous studies1,2 have
      that there is no direct correlation between overall structure and clinical
      severity.

PMID- 28490459
TI  - The heart of the matter: cardiac assessment in professional footballers.
AB  - AIM: Sudden cardiac death is the leading medical cause of death during exercise.1
      Our objective was to retrospectively analyse the routine cardiac assessment of
      professional footballers to aid physician management and improve player safety.
      METHODS: Footballers from five professional clubs between March 2012 and October
      2014 were included (n=265). All were performed in line with the recommendations
      of the Football Association Cardiology Committee, incorporating clinical
      examination, 12-lead ECG, echocardiography and health questionnaire.2 Data was
      retrospectively collected, inspected and analysed using Excel spreadsheets.
      Findings were classified as 'normal' or 'not normal', and not normal assessments
      were further broken down into 'clear-cut pathology' (pathology with widely
      accepted guidance on management) or 'grey screen'. RESULTS: Footballers were aged
      13 to 37 years, with 69% aged over 18 and 31% under. The majority of the review
      population was White European (66%). Of the review population 11% had 'not
      normal' assessments, of these assessments 83% were considered grey screens (by
      Consultant Cardiologist) requiring further investigation or surveillance. Overall
      clear-cut pathology was identified in 2%. CONCLUSIONS: A high proportion of the
      players (9%) had grey screens. The majority of these were due to ECG or
      structural abnormalities, which are clinically challenging to differentiate from
      physiological adaptation of the athletic heart and potentially fatal conditions.
      The extent to which these findings put the athlete at risk of a life threatening
      cardiac event is un-?quantified. Team physician's need to be aware of managing
      the on-going risk with these patients and ensure suitable ?follow up and
      assessment on a regular basis to mitigate this.

PMID- 28490460
TI  - Anxiety, depression and perceived sporting performance among professional cricket
      players.
AB  - BACKGROUND: Mental health in sport is a hard-hitting topic that is frequently the
      subject of news coverage and increasingly a theme for avid research. Some suggest
      that cricketers, participating in a game unique in its statistical analysis of
      individual performance, prolonged periods of play away from home and extended
      solitary game time to reflect on errors, may be especially prone to developing
      depression. This hypothesis is supported by a higher rate of suicide among male
      Test cricketers when compared with the UK male general population.1 METHODS: This
      study ascertained rates of anxiety and depression by screening professional
      cricket players using the Generalised Anxiety Disorder Questionnaire (GAD-7) and
      Patient Health Questionnaire (PHQ-9). It also investigate whether professional
      cricket players perceive stress and anxiety to be beneficial to their sporting
      performance. 21 male professional cricketers were included in this anonymous
      questionnaire based study. RESULTS: Six players had a positive depression screen,
      five scoring mild and one scoring moderate. Additionally, six players had a
      positive anxiety screen, four scoring mild and two ?players within the moderate
      range. Fifteen players thought pre-match stress and anxiety was beneficial to
      their sporting performance. Of these, nine thought slight, five thought fair and
      one thought considerable levels were optimal. CONCLUSIONS: Undiagnosed anxiety
      and depression may exist in professional cricket teams and as such better
      screening is required. The majority of players feel some level of stress and
      tension are beneficial for their performance, with a slight amount being the most
      common perceived optimum.

PMID- 28490461
TI  - Quality of life among children with spina bifida in Uganda.
AB  - BACKGROUND: Children surviving after spina bifida repair often have significant
      disability, the consequences of which may be more profound in low-income
      countries. The aim of this cross-sectional study was to measure quality of life
      (QOL) reported by children with spina bifida in Uganda, and to define factors
      associated with QOL. METHODS: QOL was measured using both the Health Utilities
      Index (HUI3) Tool and a visual analogue scale (VAS) marked from 0 to 10. In
      keeping with the WHO definition of QOL, further analysis was conducted using
      subjective QOL scores (using the VAS). Multivariate regression was used to
      investigate the association between VAS scores and prespecified variables: age,
      sex, hydrocephalus, mobility, urinary continence, school attendance and family
      size. RESULTS: Sixty two of 68 surviving children aged 10-14 were able to
      complete all aspects of the assessment. There was poor correlation between the
      VAS and HUI3 Tool (Pearson correlation 0.488). On multivariate regression, the
      following variables were associated with a significant change in the 10-point VAS
      (change in score; 95% CI): male sex (-1.45; -2.436 to -0.465), urinary continence
      (1.681; 0.190 to 3.172), large family size (-1.775; -2.773 to -0.777) and
      hydrocephalus (-1.382; -2.374 to -0.465). CONCLUSIONS: Urinary continence and
      family size are potentially modifiable, the former by simple and inexpensive
      medical management. Enhanced investment in community-based rehabilitation and
      support is urgently needed. Delivery of family planning services is a national
      priority in Uganda, and should be discussed with families as part of holistic
      care.

PMID- 28490462
TI  - Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target
      for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment.
AB  - Purpose: The past decade has witnessed the rapid development of personalized
      targeted therapies in lung cancer. It is still unclear whether epigenetic changes
      are involved in the response to tyrosine kinase inhibitor (TKI) treatment in
      epidermal growth factor receptor (EGFR)-mutated lung cancer.Experimental Design:
      Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the
      methylation changes in paired tissues before and after erlotinib treatment for 42
      days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients
      (N = 2) with EGFR 19 deletion. The Sequenom EpiTYPER assay was used to validate
      the changed methylated candidate genes. Up- or downregulation of the candidate
      gene was performed to elucidate the potential mechanism in the regulation of
      erlotinib treatment response.Results: Sixty aberrant methylated genes were
      screened using MSCC sequencing. Two aberrant methylated genes, CBFA2T3 and
      GABBR2, were clearly validated. A same differential methylated region (DMR)
      between exon 2 and exon 3 of GABBR2 gene was confirmed consistently in both
      patients. GABBR2 was significantly downregulated in EGFR 19 deletion cells,
      HCC4006 and HCC827, but remained conserved in EGFR wild-type A549 cells after
      erlotinib treatment. Upregulation of GABBR2 expression significantly rescued
      erlotinib-induced apoptosis in HCC827 cells. GABBR2 was significantly
      downregulated, along with the reduction of S6, p-p70 S6, and p-ERK1/2,
      demonstrating that GABBR2 may play an important role in EGFR signaling through
      the ERK1/2 pathway.Conclusions: We demonstrated that GABBR2 gene might be a novel
      potential epigenetic treatment target with induction erlotinib treatment for
      stage IIIa (N2) EGFR 19 deletion lung adenocarcinoma. Clin Cancer Res; 23(17);
      5003-14. (c)2017 AACR.

PMID- 28490463
TI  - A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective
      PI3Kalpha Isoform Inhibitor, in Patients with Advanced Solid Malignancies.
AB  - Purpose: To evaluate the safety, MTD, pharmacokinetics, pharmacodynamics, and
      preliminary antitumor activity of TAK-117 (MLN1117/INK1117), an investigational
      PI3Kalpha-selective inhibitor, in patients with advanced solid
      tumors.Experimental Design: Seventy-one patients received oral TAK-117 once daily
      [100-300 mg (n = 24)] or 3 days per week [Monday-Wednesday-Friday (MWF), 200
      1,200 mg (n = 27); Monday-Tuesday-Wednesday (MTuW), 200-900 mg (n = 20)], in 21
      day cycles. Dose escalation proceeded via a 3 + 3 design.Results: TAK-117 once
      daily dosing was associated with dose-limiting grade >=3 alanine/aspartate
      aminotransferase (ALT/AST) elevations, resulting in a narrow range of tolerable
      doses (100-150 mg once daily). With MWF/MTuW dosing, no dose-limiting ALT/AST
      elevations occurred until the MTD of 900 mg; total weekly dose was 2.6-fold that
      of 150 mg once daily. Drug-related grade >=3 adverse events occurred in
      25%/22%/35% (including hyperglycemia in 0%/7%/15%) of once-daily/MWF/MTuW
      patients. TAK-117 (100-1,200 mg) exhibited moderately fast oral absorption, a
      generally dose proportional increase in exposure, and plasma half-life of
      approximately 11 hours. Total weekly exposures with 900 mg MWF/MTuW dosing were
      approximately 4 times greater than with 150 mg once daily. Skin pS6 expression
      was suppressed at >=200 mg. There were 3/1/0 partial responses (once
      daily/MWF/MTuW) and 5/7/5 patients had stable disease lasting >=3 months (all
      PIK3CA mutated).Conclusions: Intermittent dosing of TAK-117 had an acceptable
      safety profile and enabled higher doses and total weekly exposures versus once
      daily dosing. Although the potential for TAK-117 as single-agent therapy appears
      limited, further evaluation in combination approaches for advanced solid tumors
      is warranted. Clin Cancer Res; 23(17); 5015-23. (c)2017 AACR.

PMID- 28490464
TI  - Perioperative COX-2 and beta-Adrenergic Blockade Improves Metastatic Biomarkers
      in Breast Cancer Patients in a Phase-II Randomized Trial.
AB  - Purpose: Translational studies suggest that excess perioperative release of
      catecholamines and prostaglandins may facilitate metastasis and reduce disease
      free survival. This trial tested the combined perioperative blockade of these
      pathways in breast cancer patients.Experimental Design: In a randomized placebo
      controlled biomarker trial, 38 early-stage breast cancer patients received 11
      days of perioperative treatment with a beta-adrenergic antagonist (propranolol)
      and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors
      and sequential blood samples were assessed for prometastatic biomarkers.Results:
      Drugs were well tolerated with adverse event rates comparable with placebo.
      Transcriptome profiling of the primary tumor tested a priori hypotheses and
      indicated that drug treatment significantly (i) decreased epithelial-to
      mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory
      transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal
      transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor
      infiltrating monocytes while increasing tumor-infiltrating B cells. Drug
      treatment also significantly abrogated presurgical increases in serum IL6 and C
      reactive protein levels, abrogated perioperative declines in stimulated IL12 and
      IFNgamma production, abrogated postoperative mobilization of CD16- "classical"
      monocytes, and enhanced expression of CD11a on circulating natural killer
      cells.Conclusions: Perioperative inhibition of COX-2 and beta-adrenergic
      signaling provides a safe and effective strategy for inhibiting multiple cellular
      and molecular pathways related to metastasis and disease recurrence in early
      stage breast cancer. Clin Cancer Res; 23(16); 4651-61. (c)2017 AACR.

PMID- 28490465
TI  - Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome
      Inhibition.
AB  - Purpose: EZH2 and EZH1, the catalytic components of polycomb repressive complex 2
      (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription
      of target genes and are implicated in the pathogenesis of various cancers
      including multiple myeloma and prostate cancer. Here, we investigated the
      preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination
      with proteasome inhibitors on multiple myeloma and prostate cancer.Experimental
      Design:In vitro and in vivo efficacy of UNC1999 and the combination with
      proteasome inhibitors was evaluated in multiple myeloma cell lines, primary
      patient cells, and in a xenograft model. RNA-seq and ChIP-seq were performed to
      uncover the targets of UNC1999 in multiple myeloma. The efficacy of the
      combination therapy was validated in prostate cancer cell lines.Results:
      Proteasome inhibitors repressed EZH2 transcription via abrogation of the RB-E2F
      pathway, thereby sensitizing EZH2-dependent multiple myeloma cells to EZH1
      inhibition by UNC1999. Correspondingly, combination of proteasome inhibitors with
      UNC1999, but not with an EZH2-specific inhibitor, induced synergistic antimyeloma
      activity in vitro Bortezomib combined with UNC1999 remarkably inhibited the
      growth of myeloma cells in vivo Comprehensive analyses revealed several direct
      targets of UNC1999 including the tumor suppressor gene NR4A1 Derepression of
      NR4A1 by UNC1999 resulted in suppression of MYC, which was enhanced by the
      combination with bortezomib, suggesting the cooperative blockade of PRC2
      function. Notably, this combination also exhibited strong synergy in prostate
      cancer cells.Conclusions: Our results identify dual inhibition of EZH2 and EZH1
      together with proteasome inhibition as a promising epigenetics-based therapy for
      PRC2-dependent cancers. Clin Cancer Res; 23(16); 4817-30. (c)2017 AACR.

PMID- 28490466
TI  - RET Signaling in Prostate Cancer.
AB  - Purpose: Large diameter perineural prostate cancer is associated with poor
      outcomes. GDNF, with its coreceptor GFRalpha1, binds RET and activates downstream
      pro-oncogenic signaling. Because both GDNF and GFRalpha1 are secreted by nerves,
      we examined the role of RET signaling in prostate cancer.Experimental Design:
      Expression of RET, GDNF, and/or GFRalpha1 was assessed. The impact of RET
      signaling on proliferation, invasion and soft agar colony formation, perineural
      invasion, and growth in vivo was determined. Cellular signaling downstream of RET
      was examined by Western blotting.Results: RET is expressed in all prostate cancer
      cell lines. GFRalpha1 is only expressed in 22Rv1 cells, which is the only line
      that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus
      GFRalpha1. Conditioned medium from dorsal root ganglia contains secreted
      GFRalpha1 and promotes transformation-related phenotypes, which can be blocked by
      anti-GFRalpha1 antibody. Perineural invasion in the dorsal root ganglion assay is
      inhibited by anti-GFRalpha antibody and RET knockdown. In vivo, knockdown of RET
      inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on
      context, but phosphorylation of p70S6 kinase is markedly increased in all cases.
      Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes.
      Finally, RET is expressed in 18% of adenocarcinomas and all three small-cell
      carcinomas examined.Conclusions: RET promotes transformation associated
      phenotypes, including perineural invasion in prostate cancer via activation of
      p70S6 kinase. GFRalpha1, which is secreted by nerves, is a limiting factor for
      RET signaling, creating a perineural niche where RET signaling can occur. Clin
      Cancer Res; 23(16); 4885-96. (c)2017 AACR.

PMID- 28490467
TI  - Dose Optimization to Minimize Radiation Risk for Children Undergoing CT and
      Nuclear Medicine Imaging Is Misguided and Detrimental.
AB  - A debate exists within the medical community on whether the linear no-threshold
      model of ionizing radiation exposure accurately predicts the subsequent incidence
      of radiogenic cancer. In this article, we evaluate evidence refuting the linear
      no-threshold model and corollary efforts to reduce radiation exposure from CT and
      nuclear medicine imaging in accord with the as-low-as-reasonably-achievable
      principle, particularly for children. Further, we review studies demonstrating
      that children are not, in fact, more radiosensitive than adults in the radiologic
      imaging dose range, rendering dose reduction for children unjustifiable and
      counterproductive. Efforts to minimize nonexistent risks are futile and a major
      source of persistent radiophobia. Radiophobia is detrimental to patients and
      parents, induces stress, and leads to suboptimal image quality and avoidance of
      imaging, thus increasing misdiagnoses and consequent harm while offering no
      compensating benefits.

PMID- 28490468
TI  - Is Tau Imaging More Than Just Upside-Down 18F-FDG Imaging?

PMID- 28490469
TI  - Management Impact of Imaging Brain Vesicular Monoamine Transporter Type 2 in
      Clinically Uncertain Parkinsonian Syndrome with 18F-AV133 and PET.
AB  - Idiopathic Parkinson disease is a common neurodegenerative disorder for which
      misdiagnosis occurs in up to 30% of patients after initial assessment and in 10%
      15% even after long-term follow-up. Vesicular monoamine transporter type 2
      (VMAT2) imaging with PET allows assessment of the integrity of the presynaptic
      dopaminergic pathway. We investigated the management impact of VMAT2 imaging in
      patients with clinically uncertain Parkinsonian syndromes. Methods: Forty-seven
      patients with clinically uncertain Parkinsonian syndromes (mean age +/- SD, 56.9
      +/- 14.9 y; age range, 21-80 y) were referred from movement disorder specialists.
      All participants underwent a 20-min PET acquisition 2 h after injection of 250
      MBq of 18F-AV-133, and the resulting images were quantitatively assessed.
      Clinical impact was recorded as high, moderate, or low based on diagnosis and
      management questionnaires completed by the referring specialists before and after
      release of the PET results. Management impact was high if there was a change in
      diagnostic category, moderate if there was a change in medication, and low if
      there was no change. Results: VMAT2 PET changed the diagnosis in 11 (23%) and
      medication in 25 (53%) participants. Management impact was high in 23%, moderate
      in 38%, and low in 39% of the participants. High diagnostic confidence increased
      from 11% of patients to 80% after the release of the scan results. Conclusion:18F
      AV-133 had substantial management impact in patients with clinically uncertain
      Parkinsonian syndromes. VMAT2 imaging with 18F-AV133 might improve diagnosis,
      prognosis, and appropriate use of medication, translating into better patient
      outcomes.

PMID- 28490470
TI  - Metal Artifact Reduction of CT Scans to Improve PET/CT.
AB  - In recent years, different metal artifact reduction methods have been developed
      for CT. These methods have only recently been introduced for PET/CT even though
      they could be beneficial for interpretation, segmentation, and quantification of
      the PET/CT images. In this study, phantom and patient scans were analyzed
      visually and quantitatively to measure the effect on PET images of iterative
      metal artifact reduction (iMAR) of CT data. Methods: The phantom consisted of 2
      types of hip prostheses in a solution of 18F-FDG and water. 18F-FDG PET/CT scans
      of 14 patients with metal implants (either dental implants, hip prostheses,
      shoulder prostheses, or pedicle screws) and 68Ga-labeled prostate-specific
      membrane antigen (68Ga-PSMA) PET/CT scans of 7 patients with hip prostheses were
      scored by 2 experienced nuclear medicine physicians to analyze clinical
      relevance. For all patients, a lesion was located in the field of view of the
      metal implant. Phantom and patients were scanned in a PET/CT scanner. The
      standard low-dose CT scans were processed with the iMAR algorithm. The PET data
      were reconstructed using attenuation correction provided by both standard CT and
      iMAR-processed CT. Results: For the phantom scans, cold artifacts were visible on
      the PET image. There was a 30% deficit in 18F-FDG concentration, which was
      restored by iMAR processing, indicating that metal artifacts on CT images induce
      quantification errors in PET data. The iMAR algorithm was useful for most
      patients. When iMAR was used, the confidence in interpretation increased or
      stayed the same, with an average improvement of 28% +/- 20% (scored on a scale of
      0%-100% confidence). The SUV increase or decrease depended on the type of metal
      artifact. The mean difference in absolute values of SUVmean of the lesions was
      3.5% +/- 3.3%. Conclusion: The iMAR algorithm increases the confidence of the
      interpretation of the PET/CT scan and influences the SUV. The added value of iMAR
      depends on the indication for the PET/CT scan, location and size/type of the
      prosthesis, and location and extent of the disease.

PMID- 28490471
TI  - Analysis of Prognostic Values of Various PET Metrics in Preoperative 18F-FDG PET
      for Early-Stage Bronchial Carcinoma for Progression-Free and Overall Survival:
      Significantly Increased Glycolysis Is a Predictive Factor.
AB  - The purpose of this study was to assess various volume-based PET quantification
      metrics, including metabolic tumor volume and total lesion glycolysis (TLG) with
      different thresholds, as well as background activity-based PET metrics
      (background-subtracted lesion activity [BSL] and background-subtracted volume) as
      prognostic markers for progression-free and overall survival (PFS and OS,
      respectively) in early-stage I and II non-small cell lung cancer (NSCLC) after
      resection. Methods: Patients (n = 133) underwent an adequate 18F-FDG PET/CT scan
      before surgery between January 2003 and December 2010. All PET activity metrics
      showed a skewed distribution and were log-transformed before calculation of the
      Pearson correlation coefficients. Survival tree analysis was used to discriminate
      between high- and low-risk patients and to select the most important prognostic
      markers. The Akaike information criterion was used to compare 2 univariate
      models. Results: Within the study time, 36 patients died from NSCLC and 26
      patients from other causes. At the end of follow-up, 70 patients were alive, with
      67 patients being free of disease. All log-transformed PET metrics showed a
      strong linear association, with a Pearson correlation coefficient between 0.703
      and 0.962. After multiple testing corrections, only 1 prognostic marker
      contributed a significant split point in the survival tree analysis. Of 10
      potential predictors including 7 PET metrics, a BSL greater than 6,852 (P =
      0.017) was chosen as split point, assigning 13 patients into a high-risk group.
      If BSL was removed from the set of predictors, a 42% TLG (TLG42%) of greater than
      4,204 (P = 0.023) was chosen as split point. When a dichotomized BSL or TLG42%
      variable was used for a univariate Cox model, the Akaike information criterion
      difference of both models was smaller than 2; therefore, the data do not provide
      evidence that 1 of the 2 prognostic factors is superior. Conclusion: Volume-based
      PET metrics correlate with PFS and OS and could be used for risk assessment in
      stage I-II NSCLC. The different PET metrics assessed in this study showed a high
      correlation; therefore, it is not surprising that there was no significant
      difference to predict PFS or OS within this study. Overall, patients with large
      and metabolically active tumors should be considered high risk and might need
      further treatment after resection. Because all analysis steps were done with the
      same data, these results should be validated on new patient data.

PMID- 28490472
TI  - 18F-FDG PET/CT for Very Early Response Evaluation Predicts CT Response in
      Erlotinib-Treated Non-Small Cell Lung Cancer Patients: A Comparison of Assessment
      Methods.
AB  - The purpose of this study was to determine which method for early response
      evaluation with 18F-FDG PET/CT performed most optimally for the prediction of
      response on a later CT scan in erlotinib-treated non-small cell lung cancer
      patients. Methods:18F-FDG PET/CT scans were obtained before and after 7-10 d of
      erlotinib treatment in 50 non-small cell lung cancer patients. The scans were
      evaluated using a qualitative approach and various semiquantitative methods
      including percentage change in SUVs, lean body mass-corrected (SUL) SULpeak,
      SULmax, and total lesion glycolysis (TLG). The PET parameters and their
      corresponding response categories were compared with the percentage change in the
      sum of the longest diameter in target lesions and the resulting response
      categories from a CT scan obtained after 9-11 wk of erlotinib treatment using
      receiver-operating-characteristic analysis, linear regression, and quadratic
      weighted kappa. Results: TLG delineation according to the PERCIST showed the
      strongest correlation to sum of the longest diameter (R = 0.564, P < 0.001),
      compared with SULmax (R = 0.298, P = 0.039) and SULpeak (R = 0.402, P = 0.005).
      For predicting progression on CT, receiver-operating-characteristic analysis
      showed area under the curves between 0.79 and 0.92, with the highest area under
      the curve of 0.92 (95% confidence interval [CI], 0.84-1.00) found for TLG
      (PERCIST). Furthermore, the use of a cutoff of 25% change in TLG (PERCIST) for
      both partial metabolic response and progressive metabolic disease, which is the
      best predictor of the CT response categories, showed a kappa-value of 0.53 (95%
      CI, 0.31-0.75). This method identifies 41% of the later progressive diseases on
      CT, with no false-positives. Visual evaluation correctly categorized 50%, with a
      kappa-value of 0.47 (95% CI, 0.24-0.70). Conclusion: TLG (PERCIST) was the
      optimal predictor of response on later CT scans, outperforming both SULpeak and
      SULmax The use of TLG (PERCIST) with a 25% cutoff after 1-2 wk of treatment
      allows us to safely identify 41% of the patients who will not benefit from
      erlotinib and stop the treatment at this time.

PMID- 28490473
TI  - Specific Imaging of Bacterial Infection Using 6"-18F-Fluoromaltotriose: A Second
      Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria.
AB  - 6"-18F-fluoromaltotriose is a PET tracer that can potentially be used to image
      and localize most bacterial infections, much like 18F-FDG has been used to image
      and localize most cancers. However, unlike 18F-FDG, 6"-18F-fluoromaltotriose is
      not taken up by inflammatory lesions and appears to be specific to bacterial
      infections by targeting the maltodextrin transporter that is expressed in gram
      positive and gram-negative strains of bacteria. Methods: 6"-18F-fluoromaltotriose
      was synthesized with high radiochemical purity and evaluated in several
      clinically relevant bacterial strains in cultures and in living mice. Results: 6"
      18F-fluoromaltotriose was taken up in both gram-positive and gram-negative
      bacterial strains. 6"-18F-fluoromaltotriose was also able to detect Pseudomonas
      aeruginosa in a clinically relevant mouse model of wound infection. The utility
      of 6"-18F-fluoromaltotriose to help monitor antibiotic therapies was also
      evaluated in rats. Conclusion: 6"-18F-fluoromaltotriose is a promising new tracer
      that has significant diagnostic utility, with the potential to change the
      clinical management of patients with infectious diseases of bacterial origin.

PMID- 28490474
TI  - The mechanics of microtubule networks in cell division.
AB  - The primary goal of a dividing somatic cell is to accurately and equally
      segregate its genome into two new daughter cells. In eukaryotes, this process is
      performed by a self-organized structure called the mitotic spindle. It has long
      been appreciated that mechanical forces must be applied to chromosomes. At the
      same time, the network of microtubules in the spindle must be able to apply and
      sustain large forces to maintain spindle integrity. Here we consider recent
      efforts to measure forces generated within microtubule networks by ensembles of
      key proteins. New findings, such as length-dependent force generation, protein
      clustering by asymmetric friction, and entropic expansion forces will help
      advance models of force generation needed for spindle function and maintaining
      integrity.

PMID- 28490475
TI  - Conservatives and Labour trade blows on NHS.

PMID- 28490477
TI  - Bilateral corneal injury after face-paint application to upper eyelids.
AB  - A 40-year-old woman with no known medical conditions or allergies presented with
      severely painful, watery eyes and blurred vision. She reported topical
      application of face-paint onto both upper eyelids prior to attending a Halloween
      party. She subsequently noticed a burning sensation, epiphora and misty vision
      within a few hours. On examination, bilateral large corneal epithelial defects
      were highlighted with fluorescein dye under cobalt-blue light. Antibiotic
      ointment, mydriatic and sodium ascorbate 10% eye-drops were given, and patient
      was advised to keep the eyelids shut to promote healing. No corneal defects were
      visible by day 4 and the patient was discharged with vision recovering to normal
      levels.

PMID- 28490476
TI  - Socioeconomic status in childhood and C reactive protein in adulthood: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Inflammation plays a central role in cardiometabolic disease and may
      represent a mechanism linking low socioeconomic status (SES) in early life and
      adverse cardiometabolic health outcomes in later life. Accumulating evidence
      suggests an association between childhood SES and adult inflammation, but
      findings have been inconsistent. METHODS: We conducted a systematic review and
      meta-analysis of observational studies to quantify the association between
      childhood (age <18 years) SES and the inflammatory marker C reactive protein
      (CRP) in adulthood. Studies were identified in Medline and Embase databases, and
      by reviewing the bibliographies of articles published from 1946 to December 2015.
      Study-specific estimates were combined into meta-analyses using random-effects
      models. RESULTS: 15 of 21 eligible studies (n=43 629) were ultimately included in
      two separate meta-analyses. Compared with those from the most advantaged
      families, participants from the least advantaged families had 25% higher CRP
      levels (ratio change in geometric mean CRP: 1.25; 95% CI 1.19 to 1.32) in
      minimally adjusted analyses. This finding was attenuated by the inclusion of
      adult body mass index (BMI) in adjusted models, suggesting BMI has a strong
      mediating role in CRP levels. CONCLUSIONS: We observed an inverse association
      between childhood SES and adulthood CRP, potentially mediated through BMI.
      Investigating how childhood SES is associated with childhood BMI and CRP would
      provide insight into the effective timing of social and clinical interventions to
      prevent cardiometabolic disease.

PMID- 28490478
TI  - Mixed cryoglobulinemia: a diagnostic and therapeutic challenge.
AB  - Mixed cryoglobulinemia is frequently secondary to hepatitis C virus infection.
      Diagnosis and therapeutic management are challenging, depending on the spectrum
      and severity of manifestations, as well as on the presence of comorbidities. We
      describe a case of a 79-year-old woman with a non-cirrhotic hepatitis C virus
      infection presenting with weakness, arthralgias, purpuric rash with left leg
      ulcerative lesions, bilateral peripheral sensorimotor polyneuropathy, renal
      impairment and cardiac failure. The investigation was compatible with a severe
      type II mixed cryoglobulinemia with multisystemic involvement, including a low
      grade B cell lymphoma and concomitant intestinal tuberculosis. Initial management
      with immunosuppressive therapy with glucocorticoids to control symptoms and
      simultaneous tuberculosis treatment was required. Unavailability of adequate
      antiviral treatment led to the need to control the severity of systemic
      manifestations with rituximab, before the effective aetiological treatment with
      sofosbuvir and ledipasvir was possible, allowing the definitive resolution of the
      disease.

PMID- 28490479
TI  - Cystic adventitial disease of the common femoral vein.
AB  - We present the case of a 46-year-old commercial pilot with a history of
      unilateral leg swelling following a flight to Geneva. Although initial clinical
      examination suggested a deep vein thrombosis, the swelling only partially
      resolved with anticoagulation and further imaging suggested the presence of
      adventitial cystic disease (ACD). The patient underwent initial anticoagulation
      to allow any thrombus to be lysed, followed by excision of the ACD from the
      venous wall and venous reconstruction. Following the excision of the ACD,
      providing the patient remains asymptomatic and further imaging finds normal
      venous anatomy, we hope the patient will discontinue anticoagulation and return
      to flying.

PMID- 28490480
TI  - A rare view: giant liver abscess with underlying liver metastases.

PMID- 28490481
TI  - Vitamin A deficiency due to chronic malabsorption: an ophthalmic manifestation of
      a systemic condition.
AB  - A 47-year-old woman presented with a 4-week history of progressive loss of
      vision, first manifesting as night blindness. Additionally, the patient reported
      frequent severe episodes of diarrhoea over the past month. Her medical history
      included end-stage renal failure for which she was currently on haemodialysis
      after a failed renal transplant, chronic pancreatitis and autonomic diabetes
      mellitus. Ophthalmological examination revealed severe bilateral corneal xerosis,
      bilateral Bitot's spots and inferior ulceration of the right cornea. A diagnosis
      of xerophthalmia due to vitamin A deficiency was made, most likely due to the
      presence of small intestinal bacterial overgrowth and the patient's chronic
      malabsorptive state. Standard management using oral vitamin A tablets was
      ineffective, resulting in the patient requiring intravenous supplementation. The
      extent of visual deterioration on presentation and the difficulties encountered
      managing the patient resulted in the patient's vision failing to improve.

PMID- 28490482
TI  - Conditional ablation of Raptor in the male germline causes infertility due to
      meiotic arrest and impaired inactivation of sex chromosomes.
AB  - Rapamycin is a clinically important drug that is used in transplantation and
      cancer therapy but which causes a number of side effects, including male
      infertility. Its canonical target, mammalian target of rapamycin complex 1
      (mTORC1), plays a key role in metabolism and binds chromatin; however, its
      precise role in the male germline has not been elucidated. Here, we inactivate
      the core component, Raptor, to show that mTORC1 function is critical for male
      meiosis and the inactivation of sex chromosomes. Disruption of the Raptor gene
      impairs chromosomal synapsis and prevents the efficient spreading of silencing
      factors into the XY chromatin. Accordingly, mRNA for XY-linked genes remains
      inappropriately expressed in Raptor-deficient mice. Molecularly, the failure to
      suppress gene expression corresponded with deficiencies in 2 repressive chromatin
      markers, H3K9 dimethylation and H3K9 trimethylation, in the XY body. Together,
      these results demonstrate that mTORC1 has an essential role in the meiotic
      progression and silencing of sex chromosomes in the male germline, which may
      explain the infertility that has been associated with such inhibitors as
      rapamycin.-Xiong, M., Zhu, Z., Tian, S., Zhu, R., Bai, S., Fu, K., Davis, J. G.,
      Sun, Z., Baur, J. A., Zheng, K., Ye, L. Conditional ablation of Raptor in the
      male germline causes infertility due to meiotic arrest and impaired inactivation
      of sex chromosomes.

PMID- 28490484
TI  - Developing a decision rule to optimise clinical pharmacist resources for
      medication reconciliation in the emergency department.
AB  - BACKGROUND: The process of obtaining a complete medication history for patients
      admitted to the hospital from the ED at hospital admission, without
      discrepancies, is error prone and time consuming. OBJECTIVES: The goal of this
      study was the development of a clinical decision rule (CDR) with a high positive
      predictive value in detecting ED patients admitted to hospital at risk of at
      least one discrepancy during regular medication history acquisition, along with
      favourable feasibility considering time and budget constraints. METHODS: Data
      were based on a previous prospective study conducted at the ED in Belgium,
      describing discrepancies in 3592 medication histories. Data were split into a
      training and a validation set. A model predicting the number of discrepancies was
      derived from the training set with negative binomial regression and was validated
      on the validation set. The performance of the model was assessed. Several CDRs
      were constructed and evaluated on positive predictive value and alert rate.
      RESULTS: The following variables were retained in the prediction model: (1) age,
      (2) gender, (3) medical discipline for which the patient was admitted, (4) degree
      of physician training, (5) season of admission, (6) type of care before
      admission, number of (7) drugs, (8) high-risk drugs, (9) drugs acting on
      alimentary tract and metabolism, (10) antithrombotics, antihaemorrhagics and
      antianaemic preparations, (11) cardiovascular drugs, (12) drugs acting on
      musculoskeletal system and (13) drugs acting on the nervous system; all recorded
      by the ED physician on admission. The final CDR resulted in an alert rate of 29%
      with a positive predictive value of 74%. CONCLUSION: The final CDR allows
      identification of the majority of patients with a potential discrepancy within a
      feasible workload for the pharmacy staff. Our CDR is a first step towards a rule
      that could be incorporated into electronic medical records or a scoring system.

PMID- 28490483
TI  - The ratio of dihomo-gamma-linolenic acid to deoxycholic acid species is a
      potential biomarker for the metabolic abnormalities in obesity.
AB  - Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays
      an important role in the development of metabolic disease. However, BAs in
      relation to fatty acids have not been fully investigated in obesity-related
      metabolic disorders. A targeted metabolomic measurement of serum BA and free
      fatty acid profiles was applied to sera of 381 individuals in 2 independent
      studies. The results showed that the ratio of dihomo-gamma-linolenic acid (DGLA)
      to deoxycholic acid (DCA) species (DCAS) was significantly increased in obese
      individuals with type 2 diabetes (T2DM) from a case-control study and decreased
      in the remission group of obese subjects with T2DM after metabolic surgery. The
      changes were closely associated with their metabolic status. These results were
      consistently confirmed in both serum and liver of mice with diet-induced obesity,
      implying that such a metabolic alteration in circulation reflects changes
      occurring in the liver. In vitro studies of human liver L-02 cell lines under BA
      treatment revealed that DCA and its conjugated form, TDCA, significantly
      inhibited mRNA expression of fatty acid transport protein 5 in the presence of
      DGLA, which was involved in hepatocyte DGLA uptake. Thus, the DGLA:DCAS ratio may
      be a promising biomarker for metabolic abnormalities in obesity.-Lei, S., Huang,
      F., Zhao, A., Chen, T., Chen, W., Xie, G., Zheng, X., Zhang, Y., Yu, H., Zhang,
      P., Rajani, C., Bao, Y., Jia, W., Jia, W. The ratio of dihomo-gamma-linolenic
      acid to deoxycholic acid species is a potential biomarker for the metabolic
      abnormalities in obesity.

PMID- 28490485
TI  - Molecular Characterization of Mycoplasma pneumoniae Infections in Two Rural
      Populations of Thailand from 2009 to 2012.
AB  - Studies on Mycoplasma pneumoniae in Thailand have focused on urban centers and
      have not included molecular characterization. In an attempt to provide a more
      comprehensive understanding of this organism, we conducted a systematic random
      sampling to identify 3,000 nasopharyngeal swab specimens collected from January
      2009 through July 2012 during population-based surveillance for influenza-like
      illness in two rural provinces. M. pneumoniae was detected by real-time PCR in
      175 (5.8%) specimens. Genotyping was performed using the major adhesion protein
      (P1) and multilocus variable-number tandem-repeat analysis (MLVA). Of the 157
      specimens typed, 97 were P1 type 1 and 60 were P1 type 2. Six different MLVA
      profiles were identified in 149 specimens, with 4/5/7/2 (40%) and 3/5/6/2 (26%)
      predominating. There was no discrete seasonality to M. pneumoniae infections.
      Examination of the 23S rRNA sequence for known polymorphisms conferring macrolide
      resistance revealed that all 141 tested to possess the genotype associated with
      macrolide susceptibility.

PMID- 28490486
TI  - Meatal Swabs Contain Less Cellular Material and Are Associated with a Decrease in
      Gram Stain Smear Quality Compared to Urethral Swabs in Men.
AB  - Urethral swabs are the samples of choice for point-of-care Gram stain testing to
      diagnose Neisseria gonorrhoeae infection and nongonococcal urethritis (NGU) in
      men. As an alternative to urethral swabs, meatal swabs have been recommended for
      the collection of urethral discharge to diagnose N. gonorrhoeae and Chlamydia
      trachomatis infection in certain populations by nucleic acid amplification
      testing (NAAT), as they involve a less invasive collection method. However, as
      meatal swabs could be sampling a reduced surface area and result in fewer
      collected epithelial cells compared to urethral swabs, the adequacy of meatal
      swab specimens to collect sufficient cellular material for Gram stain testing
      remains unknown. We enrolled 66 men who underwent either urethral or meatal
      swabbing and compared the cellular content and Gram stain failure rate. We
      measured the difference in swab cellular content using the Cepheid Xpert CT/NG
      sample adequacy control crossing threshold (SACCT) and determined the failure
      rate of Gram stain smears (GSS) due to insufficient cellular material. In the
      absence of discharge, meatal smears were associated with a significant reduction
      in cellular content (P = 0.0118), which corresponded with a GSS failure rate
      significantly higher than that for urethral swabs (45% versus 3%, respectively; P
      < 0.0001). When discharge was present, there was no difference among results from
      urethral and meatal swabs. Therefore, if GSS testing is being considered for
      point-of-care diagnosis of N. gonorrhoeae infection or NGU in men, meatal swabs
      should be avoided in the absence of a visible discharge.

PMID- 28490487
TI  - Bifidobacterium Bacteremia: Clinical Characteristics and a Genomic Approach To
      Assess Pathogenicity.
AB  - Bifidobacteria are commensals that colonize the orogastrointestinal tract and
      rarely cause invasive human infections. However, an increasing number of
      bifidobacterial blood culture isolates has lately been observed in Norway. In
      order to investigate the pathogenicity of the Bifidobacterium species responsible
      for bacteremia, we studied Bifidobacterium isolates from 15 patients for whom
      cultures of blood obtained from 2013 to 2015 were positive. We collected clinical
      data and analyzed phenotypic and genotypic antibiotic susceptibility. All
      isolates (11 Bifidobacterium longum, 2 B. breve, and 2 B. animalis isolates) were
      subjected to whole-genome sequencing. The 15 patients were predominantly in the
      extreme lower or upper age spectrum, many were severely immunocompromised, and 11
      of 15 had gastrointestinal tract-related conditions. In two elderly patients, the
      Bifidobacterium bacteremia caused a sepsis-like picture, interpreted as the cause
      of death. Most bifidobacterial isolates had low MICs (<=0.5 mg/liter) to beta
      lactam antibiotics, vancomycin, and clindamycin and relatively high MICs to
      ciprofloxacin and metronidazole. We performed a pangenomic comparison of invasive
      and noninvasive B. longum isolates based on 65 sequences available from GenBank
      and the sequences of 11 blood culture isolates from this study. Functional
      annotation identified unique genes among both invasive and noninvasive isolates
      of Bifidobacterium Phylogenetic clusters of invasive isolates were identified for
      a subset of the B. longum subsp. longum isolates. However, there was no
      difference in the number of putative virulence genes between invasive and
      noninvasive isolates. In conclusion, Bifidobacterium has an invasive potential in
      the immunocompromised host and may cause a sepsis-like picture. Using comparative
      genomics, we could not delineate specific pathogenicity traits characterizing
      invasive isolates.

PMID- 28490489
TI  - A Single Negative Result for van Quantitative PCR on Enrichment Broth Can Replace
      Five Rectal Swab Cultures in Screening for Vancomycin-Resistant Enterococci.
AB  - The increased incidence of infections by vancomycin-resistant Enterococcus (VRE)
      causes an accumulation of patients who are either colonized with VRE or flagged
      as potentially colonized with VRE. Since such patients require precautionary
      isolation upon admission to a hospital, rapid methods to establish VRE
      colonization status would improve patient care and optimize hospital operation.
      We evaluated van quantitative PCR (qPCR) on one enrichment broth as a VRE
      screening approach. We obtained 255 sets of five rectal specimens from 243
      patients. The specimens were cultured using an amoxicillin-containing enrichment
      broth. Subsequently, a chromogenic agar was incubated and suspect colonies were
      inoculated on a blood agar plate and characterized by matrix-assisted laser
      desorption ionization-time of flight (MALDI-TOF), followed by a vancomycin Etest
      in cases in which Enterococcus spp. were detected. The culturing results were
      compared with the outcome of van qPCR on all enrichment broths of the first
      rectal swab. The van qPCR was positive for 43% of the sample sets (vanA, n = 5;
      vanB, n = 101; vanA and vanB, n = 3). Based on culture data, 20 (7.8%) of the
      sets were VRE positive in at least one of five samples. The negative predictive
      value of van qPCR on the first enrichment broth was 99.3%. With a cutoff
      quantification cycle (Cq ) value of >35 to discriminate negative and positive
      samples, 87% of the negative patients can be identified within a day after
      obtaining the sample, compared to 7 days in the culturing approach. VRE screening
      using qPCR on one enrichment broth can quickly identify non-VRE-colonized
      patients and therefore decrease costs and limit unnecessary isolation
      restrictions.

PMID- 28490488
TI  - Genetic and Epidemiologic Trends of Norovirus Outbreaks in the United States from
      2013 to 2016 Demonstrated Emergence of Novel GII.4 Recombinant Viruses.
AB  - Noroviruses are the most frequent cause of epidemic acute gastroenteritis in the
      United States. Between September 2013 and August 2016, 2,715 genotyped norovirus
      outbreaks were submitted to CaliciNet. GII.4 Sydney viruses caused 58% of the
      outbreaks during these years. A GII.4 Sydney virus with a novel GII.P16
      polymerase emerged in November 2015, causing 60% of all GII.4 outbreaks in the
      2015-2016 season. Several genotypes detected were associated with more than one
      polymerase type, including GI.3, GII.2, GII.3, GII.4 Sydney, GII.13, and GII.17,
      four of which harbored GII.P16 polymerases. GII.P16 polymerase sequences
      associated with GII.2 and GII.4 Sydney viruses were nearly identical, suggesting
      common ancestry. Other common genotypes, each causing 5 to 17% of outbreaks in a
      season, included GI.3, GI.5, GII.2, GII.3, GII.6, GII.13, and GII.17 Kawasaki
      308. Acquisition of alternative RNA polymerases by recombination is an important
      mechanism for norovirus evolution and a phenomenon that was shown to occur more
      frequently than previously recognized in the United States. Continued molecular
      surveillance of noroviruses, including typing of both polymerase and capsid
      genes, is important for monitoring emerging strains in our continued efforts to
      reduce the overall burden of norovirus disease.

PMID- 28490490
TI  - Analysis of Morphologically Similar Staphylococcus aureus Colonies for Assessment
      of Phenotypic and Genotypic Correlation.

PMID- 28490491
TI  - Comparison of the Vitek MS and Bruker Matrix-Assisted Laser Desorption Ionization
      Time of Flight Mass Spectrometry Systems for Identification of Rhodococcus equi
      and Dietzia spp.
AB  - Rhodococcus equi causes pyogranulomatous pneumonia in domesticated animals and
      immunocompromised humans. Dietzia spp. are environmental bacteria that have
      rarely been associated with human infections. R. equi and Dietzia spp. are
      closely related actinomycetes. Phenotypic discrimination between R. equi and
      Dietzia on the basis of their Gram stain morphology and colony appearance is
      problematic. Matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) is a fast, reliable, and cost-effective method for
      identification of a wide variety of microorganisms. We have evaluated the
      performance of Bruker Biotyper versus that of Vitek MS for identification of a
      collection of 154 isolates identified at the source as R. equi that includes
      isolates belonging to the genus Dietzia PCR amplification of the choE gene,
      encoding a cholesterol oxidase, and 16S rRNA sequencing were considered the
      reference methods for R. equi identification. Biotyper identified 131 (85.1%) of
      the 154 isolates at the species level, and this figure increased to 152 (98.7%)
      when the species cutoff was reduced from a score of >=2.000 to >=1.750. Vitek MS
      correctly identified at the species level 130 (84.4%) isolates as long as
      bacteria were extracted with ethanol but only 35 (22.7%) isolates when samples
      were prepared by direct extraction from colonies. The two systems allowed
      differentiation between R. equi and Dietzia spp., but identification of all
      Dietzia sp. isolates at the species level needed sequencing of the 16S rRNA gene.

PMID- 28490492
TI  - Molecular Diagnosis of Orthopedic-Device-Related Infection Directly from
      Sonication Fluid by Metagenomic Sequencing.
AB  - Culture of multiple periprosthetic tissue samples is the current gold standard
      for microbiological diagnosis of prosthetic joint infections (PJI). Additional
      diagnostic information may be obtained through culture of sonication fluid from
      explants. However, current techniques can have relatively low sensitivity, with
      prior antimicrobial therapy and infection by fastidious organisms influencing
      results. We assessed if metagenomic sequencing of total DNA extracts obtained
      direct from sonication fluid can provide an alternative rapid and sensitive tool
      for diagnosis of PJI. We compared metagenomic sequencing with standard aerobic
      and anaerobic culture in 97 sonication fluid samples from prosthetic joint and
      other orthopedic device infections. Reads from Illumina MiSeq sequencing were
      taxonomically classified using Kraken. Using 50 derivation samples, we determined
      optimal thresholds for the number and proportion of bacterial reads required to
      identify an infection and confirmed our findings in 47 independent validation
      samples. Compared to results from sonication fluid culture, the species-level
      sensitivity of metagenomic sequencing was 61/69 (88%; 95% confidence interval
      [CI], 77 to 94%; for derivation samples 35/38 [92%; 95% CI, 79 to 98%]; for
      validation samples, 26/31 [84%; 95% CI, 66 to 95%]), and genus-level sensitivity
      was 64/69 (93%; 95% CI, 84 to 98%). Species-level specificity, adjusting for
      plausible fastidious causes of infection, species found in concurrently obtained
      tissue samples, and prior antibiotics, was 85/97 (88%; 95% CI, 79 to 93%; for
      derivation samples, 43/50 [86%; 95% CI, 73 to 94%]; for validation samples, 42/47
      [89%; 95% CI, 77 to 96%]). High levels of human DNA contamination were seen
      despite the use of laboratory methods to remove it. Rigorous laboratory good
      practice was required to minimize bacterial DNA contamination. We demonstrate
      that metagenomic sequencing can provide accurate diagnostic information in PJI.
      Our findings, combined with the increasing availability of portable, random
      access sequencing technology, offer the potential to translate metagenomic
      sequencing into a rapid diagnostic tool in PJI.

PMID- 28490493
TI  - Problems with the Oxford Multilocus Sequence Typing Scheme for Acinetobacter
      baumannii: Do Sequence Type 92 (ST92) and ST109 Exist?

PMID- 28490494
TI  - Structural basis for spumavirus GAG tethering to chromatin.
AB  - The interactions between a retrovirus and host cell chromatin that underlie
      integration and provirus expression are poorly understood. The prototype foamy
      virus (PFV) structural protein GAG associates with chromosomes via a chromatin
      binding sequence (CBS) located within its C-terminal region. Here, we show that
      the PFV CBS is essential and sufficient for a direct interaction with nucleosomes
      and present a crystal structure of the CBS bound to a mononucleosome. The CBS
      interacts with the histone octamer, engaging the H2A-H2B acidic patch in a manner
      similar to other acidic patch-binding proteins such as herpesvirus latency
      associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor
      residue in GAG result in global redistribution of PFV and macaque simian foamy
      virus (SFVmac) integration sites toward centromeres, dampening the resulting
      proviral expression without affecting the overall efficiency of integration. Our
      findings underscore the importance of retroviral structural proteins for
      integration site selection and the avoidance of genomic junkyards.

PMID- 28490496
TI  - Correction for Zastrow, News Feature: Is video game addiction really an
      addiction?

PMID- 28490495
TI  - Exclusion of alternative exon 33 of CaV1.2 calcium channels in heart is
      proarrhythmogenic.
AB  - Alternative splicing changes the CaV1.2 calcium channel electrophysiological
      property, but the in vivo significance of such altered channel function is
      lacking. Structure-function studies of heterologously expressed CaV1.2 channels
      could not recapitulate channel function in the native milieu of the
      cardiomyocyte. To address this gap in knowledge, we investigated the role of
      alternative exon 33 of the CaV1.2 calcium channel in heart function. Exclusion of
      exon 33 in CaV1.2 channels has been reported to shift the activation potential 
      10.4 mV to the hyperpolarized direction, and increased expression of
      CaV1.2Delta33 channels was observed in rat myocardial infarcted hearts. However,
      how a change in CaV1.2 channel electrophysiological property, due to alternative
      splicing, might affect cardiac function in vivo is unknown. To address these
      questions, we generated mCacna1c exon 33-/--null mice. These mice contained
      CaV1.2Delta33 channels with a gain-of-function that included conduction of larger
      currents that reflects a shift in voltage dependence and a modest increase in
      single-channel open probability. This altered channel property underscored the
      development of ventricular arrhythmia, which is reflected in significantly more
      deaths of exon 33-/- mice from beta-adrenergic stimulation. In vivo telemetric
      recordings also confirmed increased frequencies in premature ventricular
      contractions, tachycardia, and lengthened QT interval. Taken together, the
      significant decrease or absence of exon 33-containing CaV1.2 channels is
      potentially proarrhythmic in the heart. Of clinical relevance, human ischemic and
      dilated cardiomyopathy hearts showed increased inclusion of exon 33. However, the
      possible role that inclusion of exon 33 in CaV1.2 channels may play in the
      pathogenesis of human heart failure remains unclear.

PMID- 28490497
TI  - Protein composition of the hepatitis A virus quasi-envelope.
AB  - The Picornaviridae are a diverse family of RNA viruses including many pathogens
      of medical and veterinary importance. Classically considered "nonenveloped,"
      recent studies show that some picornaviruses, notably hepatitis A virus (HAV;
      genus Hepatovirus) and some members of the Enterovirus genus, are released from
      cells nonlytically in membranous vesicles. To better understand the biogenesis of
      quasi-enveloped HAV (eHAV) virions, we conducted a quantitative proteomics
      analysis of eHAV purified from cell-culture supernatant fluids by isopycnic
      ultracentrifugation. Amino acid-coded mass tagging (AACT) with stable isotopes
      followed by tandem mass spectrometry sequencing and AACT quantitation of peptides
      provided unambiguous identification of proteins associated with eHAV versus
      unrelated extracellular vesicles with similar buoyant density. Multiple peptides
      were identified from HAV capsid proteins (53.7% coverage), but none from
      nonstructural proteins, indicating capsids are packaged as cargo into eHAV
      vesicles via a highly specific sorting process. Other eHAV-associated proteins (n
      = 105) were significantly enriched for components of the endolysosomal system
      (>60%, P < 0.001) and included many common exosome-associated proteins such as
      the tetraspanin CD9 and dipeptidyl peptidase 4 (DPP4) along with multiple
      endosomal sorting complex required for transport III (ESCRT-III)-associated
      proteins. Immunoprecipitation confirmed that DPP4 is displayed on the surface of
      eHAV produced in cell culture or present in sera from humans with acute hepatitis
      A. No LC3-related peptides were identified by mass spectrometry. RNAi depletion
      studies confirmed that ESCRT-III proteins, particularly CHMP2A, function in eHAV
      biogenesis. In addition to identifying surface markers of eHAV vesicles, the
      results support an exosome-like mechanism of eHAV egress involving endosomal
      budding of HAV capsids into multivesicular bodies.

PMID- 28490498
TI  - Shelterin components mediate genome reorganization in response to replication
      stress.
AB  - The dynamic nature of genome organization impacts critical nuclear functions
      including the regulation of gene expression, replication, and DNA damage repair.
      Despite significant progress, the mechanisms responsible for reorganization of
      the genome in response to cellular stress, such as aberrant DNA replication, are
      poorly understood. Here, we show that fission yeast cells carrying a mutation in
      the DNA-binding protein Sap1 show defects in DNA replication progression and
      genome stability and display extensive changes in genome organization.
      Chromosomal regions such as subtelomeres that show defects in replication
      progression associate with the nuclear envelope in sap1 mutant cells. Moreover,
      high-resolution, genome-wide chromosome conformation capture (Hi-C) analysis
      revealed prominent contacts between telomeres and chromosomal arm regions
      containing replication origins proximal to binding sites for Taz1, a component of
      the Shelterin telomere protection complex. Strikingly, we find that Shelterin
      components are required for interactions between Taz1-associated chromosomal arm
      regions and telomeres. These analyses reveal an unexpected role for Shelterin
      components in genome reorganization in cells experiencing replication stress,
      with important implications for understanding the mechanisms governing
      replication and genome stability.

PMID- 28490499
TI  - Development of an optimized synthetic Notch receptor as an in vivo cell-cell
      contact sensor.
AB  - Detection and manipulation of direct cell-cell contact in complex tissues is a
      fundamental and challenging problem in many biological studies. Here, we report
      an optimized Notch-based synthetic receptor (synNQ) useful to study direct cell
      cell interactions in Drosophila With the synNQ system, cells expressing a
      synthetic receptor, which contains Notch activation machinery and a downstream
      transcriptional activator, QF, are activated by a synthetic GFP ligand expressed
      by contacting neighbor cells. To avoid cis-inhibition, mutually exclusive
      expression of the synthetic ligand and receptor is achieved using the "flippase
      out" system. Expression of the synthetic GFP ligand is controlled by the Gal4/UAS
      system for easy and broad applications. Using synNQ, we successfully visualized
      cell-cell interactions within and between most fly tissues, revealing previously
      undocumented cell-cell contacts. Importantly, in addition to detection of cells
      in contact with one another, synNQ allows for genetic manipulation in all cells
      in contact with a targeted cell population, which we demonstrate in the context
      of cell competition in developing wing disks. Altogether, the synNQ genetic
      system will enable a broad range of studies of cell contact in developmental
      biology.

PMID- 28490500
TI  - The wisdom of crowds for visual search.
AB  - Decision-making accuracy typically increases through collective integration of
      people's judgments into group decisions, a phenomenon known as the wisdom of
      crowds. For simple perceptual laboratory tasks, classic signal detection theory
      specifies the upper limit for collective integration benefits obtained by
      weighted averaging of people's confidences, and simple majority voting can often
      approximate that limit. Life-critical perceptual decisions often involve
      searching large image data (e.g., medical, security, and aerial imagery), but the
      expected benefits and merits of using different pooling algorithms are unknown
      for such tasks. Here, we show that expected pooling benefits are significantly
      greater for visual search than for single-location perceptual tasks and the
      prediction given by classic signal detection theory. In addition, we show that
      simple majority voting obtains inferior accuracy benefits for visual search
      relative to averaging and weighted averaging of observers' confidences. Analysis
      of gaze behavior across observers suggests that the greater collective
      integration benefits for visual search arise from an interaction between the
      foveated properties of the human visual system (high foveal acuity and low
      peripheral acuity) and observers' nonexhaustive search patterns, and can be
      predicted by an extended signal detection theory framework with trial to trial
      sampling from a varying mixture of high and low target detectabilities across
      observers (SDT-MIX). These findings advance our theoretical understanding of how
      to predict and enhance the wisdom of crowds for real world search tasks and could
      apply more generally to any decision-making task for which the minority of group
      members with high expertise varies from decision to decision.

PMID- 28490501
TI  - Dynamic microtubules regulate cellular contractility during T-cell activation.
AB  - T-cell receptor (TCR) triggering and subsequent T-cell activation are essential
      for the adaptive immune response. Recently, multiple lines of evidence have shown
      that force transduction across the TCR complex is involved during TCR triggering,
      and that the T cell might use its force-generation machinery to probe the
      mechanical properties of the opposing antigen-presenting cell, giving rise to
      different signaling and physiological responses. Mechanistically, actin
      polymerization and turnover have been shown to be essential for force generation
      by T cells, but how these actin dynamics are regulated spatiotemporally remains
      poorly understood. Here, we report that traction forces generated by T cells are
      regulated by dynamic microtubules (MTs) at the interface. These MTs suppress Rho
      activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde
      flow at the T-cell-substrate interface. Our results suggest a novel role of the
      MT cytoskeleton in regulating force generation during T-cell activation.

PMID- 28490502
TI  - Evidence from Fermi surface analysis for the low-temperature structure of
      lithium.
AB  - The low-temperature crystal structure of elemental lithium, the prototypical
      simple metal, is a several-decades-old problem. At 1 atm pressure and 298 K, Li
      forms a body-centered cubic lattice, which is common to all alkali metals.
      However, a low-temperature phase transition was experimentally detected to a
      structure initially identified as having the 9R stacking. This structure,
      proposed by Overhauser in 1984, has been questioned repeatedly but has not been
      confirmed. Here we present a theoretical analysis of the Fermi surface of lithium
      in several relevant structures. We demonstrate that experimental measurements of
      the Fermi surface based on the de Haas-van Alphen effect can be used as a
      diagnostic method to investigate the low-temperature phase diagram of lithium.
      This approach may overcome the limitations of X-ray and neutron diffraction
      techniques and makes possible, in principle, the determination of the lithium low
      temperature structure (and that of other metals) at both ambient and high
      pressure. The theoretical results are compared with existing low-temperature
      ambient pressure experimental data, which are shown to be inconsistent with a 9R
      phase for the low-temperature structure of lithium.

PMID- 28490503
TI  - Entropic forces drive self-organization and membrane fusion by SNARE proteins.
AB  - SNARE proteins are the core of the cell's fusion machinery and mediate virtually
      all known intracellular membrane fusion reactions on which exocytosis and
      trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form
      trans-SNARE complexes ("SNAREpins") with target membrane-associated t-SNAREs, a
      zippering-like process releasing ~65 kT per SNAREpin. Fusion requires several
      SNAREpins, but how they cooperate is unknown and reports of the number required
      vary widely. To capture the collective behavior on the long timescales of fusion,
      we developed a highly coarse-grained model that retains key biophysical SNARE
      properties such as the zippering energy landscape and the surface charge
      distribution. In simulations the ~65-kT zippering energy was almost entirely
      dissipated, with fully assembled SNARE motifs but uncomplexed linker domains. The
      SNAREpins self-organized into a circular cluster at the fusion site, driven by
      entropic forces that originate in steric-electrostatic interactions among
      SNAREpins and membranes. Cooperative entropic forces expanded the cluster and
      pulled the membranes together at the center point with high force. We find that
      there is no critical number of SNAREs required for fusion, but instead the fusion
      rate increases rapidly with the number of SNAREpins due to increasing entropic
      forces. We hypothesize that this principle finds physiological use to boost
      fusion rates to meet the demanding timescales of neurotransmission, exploiting
      the large number of v-SNAREs available in synaptic vesicles. Once in an
      unfettered cluster, we estimate >=15 SNAREpins are required for fusion within the
      ~1-ms timescale of neurotransmitter release.

PMID- 28490504
TI  - Fasciculation in amyotrophic lateral sclerosis: origin and pathophysiological
      relevance.
AB  - This review considers the origin and significance of fasciculations in
      neurological practice, with an emphasis on fasciculations in amyotrophic lateral
      sclerosis (ALS), and in benign fasciculation syndromes. Fasciculation represents
      a brief spontaneous contraction that affects a small number of muscle fibres,
      causing a flicker of movement under the skin. While an understanding of the role
      of fasciculation in ALS remains incomplete, fasciculations derive from ectopic
      activity generated in the motor system. A proximal origin seems likely to
      contribute to the generation of fasciculation in the early stages of ALS, while
      distal sites of origin become more prominent later in the disease, associated
      with distal motor axonal sprouting as part of the reinnervation response that
      develops secondary to loss of motor neurons. Fasciculations are distinct from the
      recurrent trains of axonal firing described in neuromyotonia. Fasciculation
      without weakness, muscle atrophy or increased tendon reflexes suggests a benign
      fasciculation syndrome, even when of sudden onset. Regardless of origin,
      fasciculations often present as the initial abnormality in ALS, an early
      harbinger of dysfunction and aberrant firing of motor neurons.

PMID- 28490505
TI  - Application of the CSF JCV antibody index to early natalizumab-associated
      progressive multifocal leukoencephalopathy.

PMID- 28490506
TI  - Polyadenylation is the key aspect of GLD-2 function in C. elegans.
AB  - The role of many enzymes extends beyond their dedicated catalytic activity by
      fulfilling important cellular functions in a catalysis-independent fashion. In
      this aspect, little is known about 3'-end RNA-modifying enzymes that belong to
      the class of nucleotidyl transferases. Among these are noncanonical poly(A)
      polymerases, a group of evolutionarily conserved enzymes that are critical for
      gene expression regulation, by adding adenosines to the 3'-end of RNA targets. In
      this study, we investigate whether the functions of the cytoplasmic poly(A)
      polymerase (cytoPAP) GLD-2 in C. elegans germ cells exclusively depend on its
      catalytic activity. To this end, we analyzed a specific missense mutation
      affecting a conserved amino acid in the catalytic region of GLD-2 cytoPAP.
      Although this mutated protein is expressed to wild-type levels and incorporated
      into cytoPAP complexes, we found that it cannot elongate mRNA poly(A) tails
      efficiently or promote GLD-2 target mRNA abundance. Furthermore, germ cell
      defects in animals expressing this mutant protein strongly resemble those lacking
      the GLD-2 protein altogether, arguing that only the polyadenylation activity of
      GLD-2 is essential for gametogenesis. In summary, we propose that all known
      molecular and biological functions of GLD-2 depend on its enzymatic activity,
      demonstrating that polyadenylation is the key mechanism of GLD-2 functionality.
      Our findings highlight the enzymatic importance of noncanonical poly(A)
      polymerases and emphasize the pivotal role of poly(A) tail-centered cytoplasmic
      mRNA regulation in germ cell biology.

PMID- 28490508
TI  - Longer exposure to a new refugee food ration is associated with reduced
      prevalence of small for gestational age: results from 2 cross-sectional surveys
      on the Thailand-Myanmar border.
AB  - Background: Despite the high risk of compromised nutrition, evidence of the
      effect of refugee rations on fetal growth is limited. A new ration containing
      micronutrient-fortified flour without increased caloric content of the general
      food basket was introduced to the Maela refugee camp in Thailand, July
      2004.Objective: The effect of the length of gestational exposure of the new
      ration on fetal growth was compared with birth outcomes [small for gestational
      age (SGA), preterm birth (PTB)].Design: In an observational study in 987 newborns
      from 1048 prospectively followed antenatal clinic (ANC) attendees enrolled in 2
      cross-sectional surveys, exposure was categorized in 2004 according to gestation
      at the time of commencing the new ration and in 2006 as comprehensive
      (preconception and pregnancy). In both surveys, the pregnancy-specific ration and
      vitamin supplements were routine.Results: In 2004, the proportions of SGA
      decreased with longer exposure to the new ration: no exposure during pregnancy
      (27.7%; n = 13 of 47) and exposure in the third (27.6%; n = 37 of 134), second
      (18.6%; n = 35 of 188), and first (19.4%; n = 6 of 31) trimesters, respectively
      (adjusted P-trend = 0.046). In 2006, the new ration was available to all women
      and there was no significant additional impact of the pregnancy-specific ration
      and vitamin supplements. Between 2004 and 2006, SGA decreased from 28.9% (13 of
      45) to 17.3% (69 of 398) (adjusted P = 0.050), a reduction of 40.1% (95% CI:
      34.7%, 45.9%); there was also a decrease in the percentage of underweight women
      on admission to the ANC (38.2%; 95% CI: 31.4%, 45.5%). PTB rates were low and not
      significantly different with exposure to the new ration.Conclusions: In 2004, the
      earlier in gestation in which the new ration was available the greater the effect
      on fetal growth as shown by a reduced prevalence of SGA. In 2006, additional
      benefits to fetal growth from the pregnancy-specific ration and vitamin
      supplements beyond those of the preconception ration were not observed. Good
      nutrition in pregnancy remains an important challenge for refugee populations.
      This trial was registered at http://drks-neu.uniklinik-freiburg.de/drks_web/ as
      DRKS00007736.

PMID- 28490509
TI  - Vitamin D and calcium intake and risk of early menopause.
AB  - Background: Early menopause, defined as the cessation of ovarian function before
      the age of 45 y, affects ~10% of women and is associated with higher risk of
      cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk
      factors for early menopause have been identified, but emerging data suggest that
      high vitamin D intake may reduce risk.Objective: We evaluated how intakes of
      vitamin D and calcium are associated with the incidence of early menopause in the
      prospective Nurses' Health Study II (NHS2).Design: Intakes of vitamin D and
      calcium from foods and supplements were measured every 4 y with the use of a food
      frequency questionnaire. Cases of incident early menopause were identified from
      all participants who were premenopausal at baseline in 1991; over 1.13 million
      person-years, 2041 women reported having natural menopause before the age of 45
      y. We used Cox proportional hazards regression to evaluate relations between
      intakes of vitamin D and calcium and incident early menopause while accounting
      for potential confounding factors.Results: After adjustment for age, smoking, and
      other factors, women with the highest intake of dietary vitamin D (quintile
      median: 528 IU/d) had a significant 17% lower risk of early menopause than women
      with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95);
      P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246
      mg/d) compared with the lowest (median: 556 mg/d) was associated with a
      borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76,
      1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from
      dairy sources than from nondairy dietary sources, whereas high supplement use was
      not associated with lower risk.Conclusions: Findings suggest that high intakes of
      dietary vitamin D and calcium may be modestly associated with a lower risk of
      early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations,
      other dairy constituents, and early menopause are warranted.

PMID- 28490510
TI  - Nonfermented milk and other dairy products: associations with all-cause
      mortality.
AB  - Background: A positive association between nonfermented milk intake and increased
      all-cause mortality was recently reported, but overall, the association between
      dairy intake and mortality is inconclusive.Objective: We studied associations
      between intake of dairy products and all-cause mortality with an emphasis on
      nonfermented milk and fat content.Design: A total of 103,256 adult participants
      (women: 51.0%) from Northern Sweden were included (7121 deaths; mean follow-up:
      13.7 y). Associations between all-cause mortality and reported intakes of
      nonfermented milk (total or by fat content), fermented milk, cheese, and butter
      were tested with the use of Cox proportional hazards models that were adjusted
      for age, sex, body mass index, smoking status, education, energy intake,
      examination year, and physical activity. To circumvent confounding, Mendelian
      randomization was applied in a subsample via the lactase LCT-13910 C/T single
      nucleotide polymorphism that is associated with lactose tolerance and milk
      intake.Results: High consumers of nonfermented milk (>=2.5 times/d) had a 32%
      increased hazard (HR: 1.32; 95% CI: 1.18, 1.48) for all-cause mortality compared
      with that of subjects who consumed milk <=1 time/wk. The corresponding value for
      butter was 11% (HR: 1.11; 95% CI: 1.07, 1.21). All nonfermented milk-fat types
      were independently associated with increased HRs, but compared with full-fat
      milk, HRs were lower in consumers of medium- and low-fat milk. Fermented milk
      intake (HR: 0.90; 95% CI: 0.86, 0.94) and cheese intake (HR: 0.93; 95% CI: 0.91,
      0.96) were negatively associated with mortality. Results were slightly attenuated
      by lifestyle adjustments but were robust in sensitivity analyses. Mortality was
      not significantly associated with the LCT-13910 C/T genotype in the smaller
      subsample. The amount and type of milk intake was associated with lifestyle
      variables.Conclusions: In the present Swedish cohort study, intakes of
      nonfermented milk and butter are associated with higher all-cause mortality, and
      fermented milk and cheese intakes are associated with lower all-cause mortality.
      Residual confounding by lifestyle cannot be excluded, and Mendelian randomization
      needs to be examined in a larger sample.

PMID- 28490511
TI  - Impact of breakfast skipping compared with dinner skipping on regulation of
      energy balance and metabolic risk.
AB  - Background: Meal skipping has become an increasing trend of the modern lifestyle
      that may lead to obesity and type 2 diabetes.Objective: We investigated whether
      the timing of meal skipping impacts these risks by affecting circadian regulation
      of energy balance, glucose metabolism, and postprandial inflammatory
      responses.Design: In a randomized controlled crossover trial, 17 participants
      [body mass index (in kg/m2): 23.7 +/- 4.6] underwent 3 isocaloric 24-h
      interventions (55%, 30%, and 15% carbohydrate, fat, and protein, respectively): a
      breakfast skipping day (BSD) and a dinner skipping day (DSD) separated by a
      conventional 3-meal-structure day (control). Energy and macronutrient balance was
      measured in a respiration chamber. Postprandial glucose, insulin, and
      inflammatory responses in leukocytes as well as 24-h glycemia and insulin
      secretion were analyzed.Results: When compared with the 3-meal control, 24-h
      energy expenditure was higher on both skipping days (BSD: +41 kcal/d; DSD: +91
      kcal/d; both P < 0.01), whereas fat oxidation increased on the BSD only (+16 g/d;
      P < 0.001). Spontaneous physical activity, 24-h glycemia, and 24-h insulin
      secretion did not differ between intervention days. The postprandial homeostasis
      model assessment index (+54%) and glucose concentrations after lunch (+46%) were,
      however, higher on the BSD than on the DSD (both P < 0.05). Concomitantly, a
      longer fasting period with breakfast skipping also increased the inflammatory
      potential of peripheral blood cells after lunch.Conclusions: Compared with 3
      meals/d, meal skipping increased energy expenditure. In contrast, higher
      postprandial insulin concentrations and increased fat oxidation with breakfast
      skipping suggest the development of metabolic inflexibility in response to
      prolonged fasting that may in the long term lead to low-grade inflammation and
      impaired glucose homeostasis. This trial was registered at clinicaltrials.gov as
      NCT02635139.

PMID- 28490512
TI  - Preconceptional and gestational weight trajectories and risk of delivering a
      small-for-gestational-age baby in rural Gambia.
AB  - Background: Maternal nutritional status is a key determinant of small for
      gestational age (SGA), but some knowledge gaps remain, particularly regarding the
      role of the energy balance entering pregnancy.Objective: We investigated how
      preconceptional and gestational weight trajectories (summarized by individual
      level traits) are associated with SGA risk in rural Gambia.Design: The sample
      comprised 670 women in a trial with serial weight data (7310 observations) that
      were available before and during pregnancy. Individual trajectories from 6 mo
      before conception to 30 wk of gestation were produced with the use of multilevel
      modeling. Summary traits were expressed as weight z scores [weight z score at 3
      mo preconception (zwt-3 mo), weight z score at conception, weight z score at 3 mo
      postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional
      measures that represented the change from the preceding time] and were related to
      SGA risk with the use of Poisson regression with confounder adjustment; linear
      splines were used to account for nonlinearity.Results: Maternal weight at each
      time point had a consistent nonlinear relation with SGA risk. For example, the
      zwt-3 mo estimate was stronger in women with values <=0.5 (RR: 0.736; 95% CI:
      0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241).
      The former group had the highest observed SGA prevalence. Focusing on weight
      change, only conditional zwt+7 mo was associated with SGA and only in women with
      values >-0.5 (RR: 0.579; 95% CI: 0.463, 0.724).Conclusions: Protection against
      delivering an SGA neonate offered by greater preconceptional or gestational
      weight may be most pronounced in more undernourished and vulnerable women.
      Independent of this possibility, greater second- and third-trimester weight gain
      beyond a threshold may be protective. This trial was registered at
      http://www.isrctn.com/ as ISRCTN49285450.

PMID- 28490513
TI  - Effect of maternal antenatal and newborn supplementation with vitamin A on
      cognitive development of school-aged children in rural Bangladesh: a follow-up of
      a placebo-controlled, randomized trial.
AB  - Background: The impact of early vitamin A supplementation on neurodevelopmental
      function has not been adequately studied. In rural Bangladesh we examined
      cognitive and motor function and scholastic achievement in a cohort of children
      who were exposed to vitamin A in utero or at birth.Objective: The aim of this
      study was to examine independent and combined effects of antenatal and newborn
      supplementation with vitamin A on the cognitive function of children at 8 y of
      age.Design: A cohort of rural Bangladeshi children from 2 previous double-blind,
      placebo-controlled cluster-randomized trials were revisited at age 8 y between
      February 2013 and June 2014. Data on sociodemographic, social, and physical
      conditions; schooling; child care behavior; anthropometric measures; and
      cognitive function were collected with the use of various psychometric assessment
      tools.Results: Among 11,950 children from the parent trial who were last known to
      be alive, a subset of 1803 children balanced by treatment group in a selected
      contiguous study area were re-enrolled and 1613 (89%) provided consent for
      assessments. Of these, 1577 (87%) children had a complete cognitive evaluation.
      All groups were highly comparable on baseline variables collected in the previous
      trials and factors measured at re-enrollment. Overall, there was no impact of
      either maternal or newborn supplementation with vitamin A on intelligence,
      memory, and motor function. Compared with placebo, children who received both
      interventions had significantly better performance in reading, spelling, and math
      computation, with increased mean (95% CI) scores of 8.0 (2.2, 13.8), 6.8 (1.9,
      11.7), and 4.8 (0.6, 9.0), respectively.Conclusions: General intelligence or
      memory and motor functions were not affected by antenatal or newborn
      supplementation with vitamin A. Scholastic performance and aspects of executive
      function improved when both interventions were provided. These trials were
      registered at clinicaltrials.gov as NCT00198822 and NCT00128557.

PMID- 28490514
TI  - Vitamin D supplementation has no effect on insulin sensitivity or secretion in
      vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled
      trial.
AB  - Background: Vitamin D supplementation has been proposed as a potential strategy
      to prevent type 2 diabetes. Existing clinical trials have been limited by short
      duration, low doses of vitamin D, variability in participants' vitamin D
      deficiency status, and the use of surrogate measures of body composition, insulin
      sensitivity, and insulin secretion.Objective: To address existing knowledge gaps,
      we conducted a double-blind, randomized, placebo-controlled trial to investigate
      whether vitamin D supplementation that is provided in a sufficient dose and
      duration to vitamin D-deficient individuals would improve insulin sensitivity or
      secretion as measured with the use of gold-standard methods. We hypothesized that
      vitamin D supplementation would improve insulin sensitivity and secretion
      compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient
      (25-hydroxyvitamin D [25(OH)D] concentration <=50 nmol/L) adults were randomly
      assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol
      followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and
      after the intervention, participants received gold-standard assessments of body
      composition (via dual X-ray absorptiometry), insulin sensitivity (via
      hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous
      glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the
      study [35 men and 19 women; mean +/- SD age: 31.9 +/- 8.5 y; body mass index (in
      kg/m2): 30.9 +/- 4.4]. 25(OH)D increased with vitamin D supplementation compared
      with placebo (57.0 +/- 21.3 compared with 1.9 +/- 15.1 nmol/L, respectively; P =
      0.02). Vitamin D and placebo groups did not differ in change in insulin
      sensitivity (0.02 +/- 2.0 compared with -0.03 +/- 2.8 mg . kg-1 . min-1,
      respectively; P = 0.9) or first-phase insulin secretion (-21 +/- 212 compared
      with 24 +/- 184 mU/L, respectively; P = 0.9). Results remained nonsignificant
      after adjustment for age, sex, percentage of body fat, sun exposure, physical
      activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D
      supplementation does not improve insulin sensitivity or secretion in vitamin D
      deficient, overweight or obese adults, despite using high-dose vitamin D
      supplementation and robust endpoint measures. Therefore, it is unlikely that
      vitamin D supplementation would be an effective strategy for reducing diabetes
      risk even in vitamin D-deficient populations. This trial was registered at
      clinicaltrials.gov as NCT02112721.

PMID- 28490515
TI  - The effect of oral iron with or without multiple micronutrients on hemoglobin
      concentration and hemoglobin response among nonpregnant Cambodian women of
      reproductive age: a 2 x 2 factorial, double-blind, randomized controlled
      supplementation trial.
AB  - Background: Despite a high prevalence of anemia among nonpregnant Cambodian
      women, current reports suggest that iron deficiency (ID) prevalence is low. If
      true, iron supplementation will not be an effective anemia reduction
      strategy.Objective: We measured the effect of daily oral iron with or without
      multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant
      Cambodian women screened as anemic.Design: In this 2 * 2 factorial, double-blind,
      randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations
      <=117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang
      province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs
      (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo
      capsules. A 2 * 2 factorial intention-to-treat analysis with the use of a
      generalized mixed-effects model was used to assess the effects of iron and MMNs
      and the interaction between these factors. Results: In July 2015, 809 women were
      recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58%
      (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN,
      Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123),
      and 116 (116, 117) g/L, with no iron * MMN interaction (P = 0.66). Mean (95% CI)
      increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) (P < 0.001) among women who
      received iron (n = 407) and 1.2 g/L (-0.6, 3.0 g/L) (P = 0.18) among women who
      received MMNs (n = 407). The predicted proportions (95% CIs) of women with a
      hemoglobin response (>=10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30%
      (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups,
      respectively.Conclusions: Daily iron supplementation for 12 wk increased
      hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer
      additional significant benefit. Overall, ~24% of women who received iron
      responded after 12 wk; even fewer would be likely to respond in the wider
      population. This trial was registered at clinicaltrials.gov as NCT02481375.

PMID- 28490516
TI  - The positive impact of general vitamin D food fortification policy on vitamin D
      status in a representative adult Finnish population: evidence from an 11-y follow
      up based on standardized 25-hydroxyvitamin D data.
AB  - Background: A systematic vitamin D fortification of fluid milk products and fat
      spreads was started in 2003 in Finland to improve vitamin D status. Objective: We
      investigated the effects of the vitamin D fortification policy on vitamin D
      status in Finland between 2000 and 2011.Design: Serum 25-hydroxyvitamin D [S
      25(OH)D] concentrations of a nationally representative sample comprising 6134 and
      4051 adults aged >=30 y from the Health 2000 and Health 2011 surveys,
      respectively, were standardized according to the Vitamin D Standardization
      Program with the use of liquid chromatography-tandem mass spectrometry. Linear
      and logistic regression models were used to assess the change in S-25(OH)D
      concentrations.Results: Between 2000 and 2011, the mean S-25(OH)D increased from
      48 nmol/L (95% CI: 47, 48 nmol/L) to 65 nmol/L (95% CI: 65, 66 nmol/L) (P <
      0.001). The prevalence of vitamin D supplement users increased from 11% to 41% (P
      < 0.001). When analyzing the effect of fortification of fluid milk products, we
      focused on supplement nonusers. The mean increase in S-25(OH)D in daily fluid
      milk consumers (n = 1017) among supplement nonusers was 20 nmol/L (95% CI: 19, 21
      nmol/L), which was 6 nmol/L higher than nonconsumers (n = 229) (14 nmol/L; 95%
      CI: 12, 16 nmol/L) (P < 0.001). In total, 91% of nonusers who consumed fluid milk
      products, fat spreads, and fish based on Finnish nutrition recommendations
      reached S-25(OH)D concentrations >50 nmol/L in 2011.Conclusions: The vitamin D
      status of the Finnish adult population has improved considerably during the time
      period studied. The increase is mainly explained by food fortification,
      especially of fluid milk products, and augmented vitamin D supplement use. Other
      factors, such as the difference in the ultraviolet radiation index between 2000
      and 2011, may partly explain the results. When consuming vitamin D sources based
      on the nutritional recommendations, vitamin D status is sufficient [S-25(OH)D
      >=50 nmol/L], and supplementation is generally not needed.

PMID- 28490517
TI  - ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog
      Subgroup Medulloblastomas.
AB  - Medulloblastoma arising from the cerebellum is the most common pediatric brain
      malignancy, with leptomeningeal metastases often present at diagnosis and
      recurrence associated with poor clinical outcome. In this study, we used mouse
      medulloblastoma models to explore the relationship of tumor pathophysiology and
      dysregulated expression of the NOTCH pathway transcription factor ATOH1, which is
      present in aggressive medulloblastoma subtypes driven by aberrant Sonic
      Hedgehog/Patched (SHH/PTCH) signaling. In experiments with conditional ATOH1
      mouse mutants crossed to Ptch1+/- mice, which develop SHH-driven medulloblastoma,
      animals with Atoh1 transgene expression developed highly penetrant
      medulloblastoma at a young age with extensive leptomeningeal disease and
      metastasis to the spinal cord and brain, resembling xenografts of human SHH
      medulloblastoma. Metastatic tumors retained abnormal SHH signaling like tumor
      xenografts. Conversely, ATOH1 expression was detected consistently in recurrent
      and metastatic SHH medulloblastoma. Chromatin immunoprecipitation sequencing and
      gene expression profiling identified candidate ATOH1 targets in tumor cells
      involved in development and tumorigenesis. Among these targets specific to
      metastatic tumors, there was an enrichment in those implicated in extracellular
      matrix remodeling activity, cytoskeletal network and interaction with
      microenvironment, indicating a shift in transcriptomic and epigenomic landscapes
      during metastasis. Treatment with bone morphogenetic protein or SHH pathway
      inhibitors decreased tumor cell proliferation and suppressed metastatic tumor
      growth, respectively. Our work reveals a dynamic ATOH1-driven molecular cascade
      underlying medulloblastoma metastasis that offers possible therapeutic
      opportunities. Cancer Res; 77(14); 3766-77. (c)2017 AACR.

PMID- 28490519
TI  - Multiple factors influence population sex ratios in the Mojave Desert moss
      Syntrichia caninervis.
AB  - PREMISE OF RESEARCH: Natural populations of many mosses appear highly female
      biased based on the presence of reproductive structures. This bias could be
      caused by increased male mortality, lower male growth rate, or a higher threshold
      for achieving sexual maturity in males. Here we test these hypotheses using
      samples from two populations of the Mojave Desert moss Syntrichia caninervis.
      METHODS: We used double-digest restriction-site associated DNA (RAD) sequencing
      to identify candidate sex-associated loci in a panel of sex-expressing plants.
      Next, we used putative sex-associated markers to identify the sex of individuals
      without sex structures. KEY RESULTS: We found a 17:1 patch-level phenotypic
      female to male sex ratio in the higher elevation site (Wrightwood) and no sex
      expression at the low elevation site (Phelan). In contrast, on the basis of
      genetic data, we found a 2:1 female bias at the Wrightwood site and only females
      at the Phelan site. The relative area occupied by male and female genets was
      indistinguishable, but males were less genetically diverse. CONCLUSIONS: Our data
      suggest that both male-biased mortality and sexual dimorphism in thresholds for
      sex expression could explain genetic and phenotypic sex ratio biases and that
      phenotypic sex expression alone over-estimates the extent of actual sex ratio
      bias present in these two populations of S. caninervis.

PMID- 28490518
TI  - CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in
      Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or
      Olaparib.
AB  - Effective targeted therapies for small-cell lung cancer (SCLC), the most
      aggressive form of lung cancer, remain urgently needed. Here we report evidence
      of preclinical efficacy evoked by targeting the overexpressed cell-cycle
      checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or
      pharmacologic blockade with the novel second-generation CHK1 inhibitor
      prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro
      and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the
      effects of cisplatin or the PARP inhibitor olaparib, and improved the response of
      platinum-resistant models. Proteomic analysis identified CHK1 and MYC as top
      predictive biomarkers of LY2606368 sensitivity, suggesting that CHK1 inhibition
      may be especially effective in SCLC with MYC amplification or MYC protein
      overexpression. Our findings provide a preclinical proof of concept supporting
      the initiation of a clinical efficacy trial in patients with platinum-sensitive
      or platinum-resistant relapsed SCLC. Cancer Res; 77(14); 3870-84. (c)2017 AACR.

PMID- 28490520
TI  - Carbon allocation to growth and storage in two evergreen species of contrasting
      successional status.
AB  - PREMISE OF THE STUDY: A prevailing hypothesis in forest succession is that shade
      tolerant species grow more slowly than shade-intolerant species, across light
      conditions, because they prioritize carbon (C) allocation to storage. We examined
      this hypothesis in a confamilial pair of species, including one of the fastest
      growing tree species in the world (Eucalyptus globulus) and a shade-tolerant,
      slow-growing species (Luma apiculata). METHODS: Seedlings were subjected to one
      out of four combinations of light (high vs. low) and initial defoliation (90%
      defoliated vs. nondefoliated) for four months. Growth, C storage concentration in
      different organs, leaf shedding, and lateral shoot formation were measured at the
      end of the experiment. KEY RESULTS: Eucalyptus globulus grew faster than L.
      apiculata in high light, but not in low light. Both species had lower C storage
      concentration in low than in high light, but similar C storage concentrations in
      each light condition. Defoliation had no effect on C storage, except in the case
      of the old leaves of both species, which showed lower C storage levels in
      response to defoliation. Across treatments, leaf shedding was 96% higher in E.
      globulus than in L. apiculata while, in contrast, lateral shoot formation was 87%
      higher in L. apiculata. CONCLUSIONS: In low light, E. globulus prioritized C
      storage instead of growth, whereas L. apiculata prioritized growth and lateral
      branching. Our results suggest that shade tolerance depends on efficient light
      capture rather than C conservation traits.

PMID- 28490521
TI  - Survival in Women Versus Men Following Implantation of Pacemakers,
      Defibrillators, and Cardiac Resynchronization Therapy Devices in a Large,
      Nationwide Cohort.
AB  - BACKGROUND: Whether outcomes differ between sexes following treatment with
      pacemakers (PM), implantable cardioverter defibrillators, and cardiac
      resynchronization therapy (CRT) devices is unclear. METHODS AND RESULTS:
      Consecutive US patients with newly implanted PM, implantable cardioverter
      defibrillators, and CRT devices from a large remote monitoring database between
      2008 and 2011 were included in this observational cohort study. Sex-specific all
      cause survival postimplant was compared within each device type using a
      multivariable Cox proportional hazards model, stratified on age and adjusted for
      remote monitoring utilization and ZIP-based socioeconomic variables. A total of
      269 471 patients were assessed over a median 2.9 [interquartile range, 2.2, 3.6]
      years. Unadjusted mortality rates (MR; deaths/100 000 patient-years) were similar
      between women versus men receiving PMs (n=115 076, 55% male; MR 4193 versus MR
      4256, respectively; adjusted hazard ratio, 0.87; 95% CI, 0.84-0.90; P<0.001) and
      implantable cardioverter defibrillators (n=85 014, 74% male; MR 4417 versus MR
      4479, respectively; adjusted hazard ratio, 0.98; 95% CI, 0.93-1.02; P=0.244). In
      contrast, survival was superior in women receiving CRT defibrillators (n=61 475,
      72% male; MR 5270 versus male MR 7175; adjusted hazard ratio, 0.73; 95% CI, 0.70
      0.76; P<0.001) and also CRT pacemakers (n=7906, 57% male; MR 5383 versus male MR
      7625, adjusted hazard ratio, 0.69; 95% CI, 0.61-0.78; P<0.001). This relative
      difference increased with time. These results were unaffected by age or remote
      monitoring utilization. CONCLUSIONS: Women accounted for less than 30% of high
      voltage implants and fewer than half of low-voltage implants in a large, nation
      wide cohort. Survival for women and men receiving implantable cardioverter
      defibrillators and PMs was similar, but dramatically greater for women receiving
      both defibrillator- and PM-based CRT.

PMID- 28490522
TI  - Lifestyle and Risk of Screening-Detected Abdominal Aortic Aneurysm in Men.
AB  - BACKGROUND: Modifiable lifestyle-related factors associated with risk of
      abdominal aortic aneurysm (AAA) are rarely investigated with a prospective
      design. We aimed to study possible associations among such factors and
      comorbidities with mean abdominal aortic diameter (AAD) and with risk of AAA
      among men screened for the disease. METHODS AND RESULTS: Self-reported lifestyle
      related exposures were assessed at baseline (January 1, 1998) among 14 249 men
      from the population-based Cohort of Swedish Men, screened for AAA between 65 and
      75 years of age (mean 13 years after baseline). Multivariable prediction of mean
      AAD was estimated with linear regression, and hazard ratios (HRs) of AAA (AAD
      >=30 mm) with Cox proportional hazard regression. The AAA prevalence was 1.2%
      (n=168). Smoking, body mass index, and cardiovascular disease were associated
      with a larger mean AAD, whereas consumption of alcohol and diabetes mellitus were
      associated with a smaller mean AAD. The HR of AAA was increased among
      participants who were current smokers with >=25 pack-years smoked compared with
      never smokers (HR 15.59, 95% CI 8.96-27.15), those with a body mass index >=25
      versus <25 (HR 1.89, 95% CI, 1.22-2.93), and those with cardiovascular disease
      (HR 1.77, 95% CI, 1.13-2.77), and hypercholesterolemia (HR 1.59, 95% CI 1.08
      2.34). Walking or bicycling for >40 minutes/day (versus almost never) was
      associated with lower AAA hazard (HR 0.59, 95% CI 0.36-0.97) compared with almost
      never walking or bicycling. CONCLUSIONS: This prospective study confirms that
      modifiable lifestyle-related factors are associated with AAD and with AAA
      disease.

PMID- 28490523
TI  - Race-Sex Differences in Statin Use and Low-Density Lipoprotein Cholesterol
      Control Among People With Diabetes Mellitus in the Reasons for Geographic and
      Racial Differences in Stroke Study.
AB  - BACKGROUND: Statin therapy is a cornerstone of cardiovascular disease risk
      reduction for people with diabetes mellitus. Past reports have shown race-sex
      differences in statin use in general populations, but statin patterns by race and
      sex in those with diabetes mellitus have not been thoroughly studied. METHODS AND
      RESULTS: Our sample of 4288 adults >=45 years of age with diagnosed diabetes
      mellitus who had low-density lipoprotein cholesterol (LDL-C) >100 mg/dL or were
      taking statins recruited for the Reasons for Geographic and Racial Differences in
      Stroke study from 2003 to 2007. Exposures included race-sex groups (white men
      [WM], black men [BM], white women [WW], black women [BW]) and factors that may
      influence healthcare utilization. Proportions and prevalence ratios were
      calculated for statin use and LDL-C control. Statin use for WM, BM, WW, and BW
      was 66.0%, 57.8%, 55.0%, and 53.6%, respectively (P<0.001). After adjustment for
      healthcare utilization factors, statin use was lower for BM, WW, and BW compared
      with WM (prevalence ratios [95%CI]: 0.96 [0.89-1.03], 0.86 [0.80-0.92], and 0.87
      [0.81-0.93], respectively, P<0.001). LDL-C control among those taking statins for
      WM, BM, WW, and BW was 75.3%, 62.7%, 69.0%, and 56.0%, respectively (P<0.001).
      After adjustment, LDL-C control was lower for BM, WW, and BW compared with WM
      (prevalence ratios [95%CI]: 0.85 [0.79-0.93], 0.89 [0.82-0.96], and 0.73 [0.67
      0.80], respectively, P<0.001). CONCLUSIONS: Race-sex disparities in statin use
      and LDL-C control were only partly explained by factors influencing health
      services utilization. Healthcare provider awareness of these disparities may help
      to close the observed race-sex gaps in statin use and LDL-C control among people
      with diabetes mellitus.

PMID- 28490524
TI  - Patients With Heart Failure Readmitted to the Original Hospital Have Better
      Outcomes Than Those Readmitted Elsewhere.
AB  - BACKGROUND: Up to one fifth of readmissions after a heart failure hospitalization
      occur at a different hospital. This negatively impacts information continuity,
      but whether site of readmission impacts subsequent outcomes is unclear. METHODS
      AND RESULTS: Retrospective cohort study of all patients discharged with a primary
      diagnosis of heart failure in Canada between April 2004 and December 2013. We
      compared patients readmitted within 30 days to the original hospital versus a
      different hospital. Of the 217 039 heart failure patients (mean age, 76.8 years,
      50.1% male), 39 368 (18.1%) were readmitted within 30 days-32 771 (83.2%) to the
      original hospital and 6597 (16.8%) to a different hospital (increasing over time
      from 15.6% in 2004 to 18.5% by 2013; P for trend=0.001). Patients readmitted to
      different hospitals were younger and were more likely to be male, have a rural
      residence, a more-recent discharge year, an index hospitalization at a teaching
      hospital, and to be brought in by ambulance at the time of the readmission.
      Readmissions to the original hospital were substantially shorter (mean, 10.4 days
      [95% CI, 10.3-10.6] versus 11.6 days [95% CI, 11.3-12.0]; adjusted means, 11.0
      versus 12.0; P<0.0001) and had lower mortality (14.4% versus 15.0%; adjusted odds
      ratio, 0.89; 95% CI, 0.82-0.96) than readmissions to different hospitals.
      CONCLUSIONS: Readmissions to a different hospital are becoming more frequent over
      time and are associated with longer stays and higher mortality rates than
      readmissions to the original hospital. Our findings provide further evidence that
      care fragmentation may be deleterious for patients with heart failure.

PMID- 28490525
TI  - Five health issues that have dominated general elections.

PMID- 28490527
TI  - Reversible plasticity of detrusor smooth muscle: evidence for a key role of
      "slipping" actomyosin cross-bridges in the control of urinary bladder compliance.

PMID- 28490526
TI  - ATP-citrate lyase is essential for high glucose-induced histone hyperacetylation
      and fibrogenic gene upregulation in mesangial cells.
AB  - The goal of this study was to address the role of ATP-citrate lyase (ACL), an
      enzyme that converts citrate to acetyl-CoA, in high glucose (HG)-induced histone
      acetylation and profibrotic gene expression. Our recent ChIP-Seq studies have
      demonstrated that HG induces genome-wide histone hyperacetylation in mesangial
      cells (MCs). Here, we showed that exposure of MCs to HG markedly increased
      histone acetylation at the H3K9/14 and H3K18 marks and induced the expression of
      potent profibrotic factors TGF-beta1, TGF-beta3, and connective tissue growth
      factor (CTGF). The induction of these profibrotic factors was further enhanced by
      histone deacetylase inhibitor but suppressed by histone acetyl-transferase
      inhibitor, confirming the importance of histone acetylation in this regulation.
      Interestingly, HG not only upregulated ACL expression but also promoted ACL
      nuclear translocation, evidenced by increased ACL concentration and activity in
      the nuclear extracts. Consistent with this observation, transfection of MCs with
      a plasmid-carrying green fluorescent protein (GFP)-ACL fusion protein led to GFP
      nuclear accumulation when cultured in HG condition. Silencing ACL with siRNAs
      alleviated HG-induced histone hyperacetylation, as well as upregulation of TGF
      beta1, TGF-beta3, CTGF, and extracellular matrix (ECM) proteins fibronectin and
      collagen type IV, whereas ACL overexpression further enhanced HG induction of
      histone acetylation, as well as these profibrotic factors and ECM proteins.
      Collectively, these observations demonstrate that HG promotes ACL expression and
      translocation into the nucleus, where ACL converts citrate to acetyl-CoA to
      provide the substrate for histone acetylation, leading to upregulation of
      fibrogenic genes. Therefore, ACL plays a critical role in epigenetic regulation
      of diabetic renal fibrosis.

PMID- 28490529
TI  - Effect of sodium nitrite on renal function and sodium and water excretion and
      brachial and central blood pressure in healthy subjects: a dose-response study.
AB  - Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has
      vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2
      on hemodynamics, sodium excretion, and glomerular filtration rate (GFR). In a
      single-blinded, placebo-controlled, crossover study, we infused placebo (0.9%
      NaCl) or 0.58, 1.74, or 3.48 MUmol NaNO2.kg-1.h-1 for 2 h in 12 healthy subjects,
      after 4 days of a standard diet. Subjects were supine and water loaded. We
      measured brachial and central blood pressure (BP), plasma concentrations of
      renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma
      nitrite (P-[Formula: see text]), GFR by Cr-EDTA clearance, fractional excretion
      of sodium (FENa) free water clearance (CH2O), and urinary excretion rate of
      guanosine 3',5'-cyclic monophosphate (U-cGMP). The highest dose reduced brachial
      systolic BP (5.6 mmHg, P = 0.003), central systolic BP (5.6 mmHg, P = 0.035), and
      CH2O (maximum change from 3.79 to 1.27 ml/min, P = 0.031) and increased P
      [Formula: see text] (from 0.065 to 0.766 MUmol/l, P < 0.001), while reducing U
      cGMP (from 444 to 247 pmol/min, P = 0.004). GFR, FENa, P-AVP, and the components
      in the renin-angiotensin-aldosterone system did not change significantly. In
      conclusion, intravenous NaNO2 induced a dose-dependent reduction of brachial and
      central BP. The hemodynamic effect was not mediated by the renin-angiotensin
      aldosterone system. NaNO2 infusion resulted in a vasopressin-independent decrease
      in CH2O and urine output but no change in urinary sodium excretion or GFR. The
      lack of increase in cGMP accompanying the increase in [Formula: see text]
      suggests a direct effect of nitrite or nitrate on the renal tubules and vascular
      bed with little or no systemic conversion to NO.

PMID- 28490528
TI  - Combining new tools to assess renal function and morphology: a holistic approach
      to study the effects of aging and a congenital nephron deficit.
AB  - Recently, new methods for assessing renal function in conscious mice
      (transcutaneous assessment) and for counting and sizing all glomeruli in whole
      kidneys (MRI) have been described. In the present study, these methods were used
      to assess renal structure and function in aging mice, and in mice born with a
      congenital low-nephron endowment. Age-related nephron loss was analyzed in adult
      C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in
      glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant
      mice. Renal function was measured through the transcutaneous quantitation of
      fluorescein isothiocyanate-sinistrin half-life (t1/2) in conscious mice. MRI was
      used to image, count, and size cationic-ferritin labeled glomeruli in whole
      kidneys ex vivo. Design-based stereology was used to validate the MRI
      measurements of glomerular number and mean volume. In adult C57BL/6 mice, older
      age was associated with fewer and larger glomeruli, and a rightward shift in the
      glomerular size distribution. These changes coincided with a decrease in renal
      function. GNDF HET mice had a congenital nephron deficit that was associated with
      glomerular hypertrophy and exacerbated by aging. These findings suggest that
      glomerular hypertrophy and hyperfiltration are compensatory processes that can
      occur in conjunction with both age-related nephron loss and congenital nephron
      deficiency. The combination of measurement of renal function in conscious animals
      and quantitation of glomerular number, volume, and volume distribution provides a
      powerful new tool for investigating aspects of renal aging and functional
      changes.

PMID- 28490530
TI  - IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal
      mesothelial cells possibly through the JAK2/STAT3 signaling pathway.
AB  - Long-term peritoneal dialysis (PD) therapy results in functional and structural
      alteration of the peritoneal membrane, including epithelial-to-mesenchymal
      transition (EMT). Interleukin 6 (IL-6) is a local pleiotropic cytokine,
      hypothesized to play an important role in EMT. This study was designed to
      investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long
      term PD patients by assessing the level of IL-6 in dialysate and exploring the
      relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT,
      using in vitro cellular and molecular techniques. Plasma and dialysate levels of
      IL-6 were significantly higher in PD ultrafiltration failure patients compared
      with patients without ultrafiltration failure and were negatively correlated with
      measures of PD adequacy. In vitro IL-6 treatment changed human peritoneal
      mesothelial cell phenotype from a typical cobblestone-like to a fibroblast-like
      appearance and increased cell viability. IL-6 treatment increased alpha-smooth
      muscle actin and vascular endothelial growth factor expression but decreased E
      cadherin expression. IL-6 treatment activated the JAK/STAT signaling pathway.
      However, the JAK2/STAT3 inhibitor WP1066 prevented IL-6-induced activation of the
      JAK2/STAT3 pathway and EMT. We conclude that IL-6 promotes the EMT process,
      possibly by activating the JAK2/STAT3 signaling pathway. IL-6 may serve as a
      novel therapeutic target for preventing EMT, and preservation of the peritoneal
      membrane may arise from these studies.

PMID- 28490531
TI  - The effects of angiotensin-(1-7) on the exchanger NHE3 and on [Ca2+]i in the
      proximal tubules of spontaneously hypertensive rats.
AB  - The acute effects of angiotensin-1-7 [ANG-(1-7)] on the reabsorptive bicarbonate
      flow (J[Formula: see text]) were evaluated using stationary microperfusion in
      vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their
      normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive
      to H+ In WKY rats, the control J[Formula: see text] was 2.40 +/- 0.10 nmol.cm-2.s
      1 (n = 120); losartan (10-7 M) or A779 (10-6 M, a specific Mas antagonist), alone
      or in combination with losartan, decreased the J[Formula: see text] ANG-(1-7) had
      biphasic effects on J[Formula: see text]: at 10-9 M, it inhibited, and at 10-6,
      it stimulated the flow. S3226 [10-6 M, a specific Na+-H+ exchanger 3 (NHE3)
      antagonist] decreased J[Formula: see text] and changed the stimulatory effect of
      ANG-(1-7) to an inhibitory one but did not alter the inhibitory action of ANG-(1
      7). In SHR, the control J[Formula: see text] was 2.04 +/- 0.13 nmol.cm-2.s-1 (n =
      56), and A779 and/or losartan reduced the flow. ANG-(1-7) at 10-9 M increased
      J[Formula: see text], and ANG-(1-7) at 10-6 M reduced it. The effects of A779,
      losartan, and S3226 on the J[Formula: see text] were similar to those found in
      WKY rats, which indicated that in SHR, the ANG-(1-7) action on the NHE3 was via
      Mas and ANG II type 1. The cytosolic calcium in the WKY or SHR rats was ~100 nM
      and was increased by ANG-(1-7) at 10-9 or 10-6 M. In hypertensive animals, a high
      plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated
      the hypertension caused by the high plasma level of ANG II.

PMID- 28490534
TI  - Malaria Transmission and Prospects for Malaria Eradication: The Role of the
      Environment.
AB  - Environmental factors affect the transmission intensity, seasonality, and
      geographical distribution of malaria, and together with the vector, the human,
      and the parasite compose the malaria system. Strategies that alter the
      environment are among the oldest interventions for malaria control, but currently
      are not the most prominent despite historical evidence of their effectiveness.
      The importance of environmental factors, the role they play considering the
      current goals of malaria eradication, the different strategies that can be
      adopted, and the current challenges for their implementation are discussed. As
      malaria elimination/eradication takes a prominent place in the health agenda, an
      integrated action, addressing all elements of the malaria system, which
      contributes to improved knowledge and to building local capacity and that brings
      about positive effects to the health of the local population has the greatest
      chance to produce fast, effective, and sustainable results.

PMID- 28490533
TI  - The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome
      after kidney transplantation.
AB  - Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine,
      and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest
      in this pathway because of its proinflammatory nature, and drugs interfering in
      it have received increasing attention. We aimed to investigate whether serum and
      urinary parameters of the tryptophan/kynurenine pathway, and particularly
      cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long
      term outcome in renal transplant recipients (RTR). Data were collected in
      outpatient RTR with a functioning graft for >1 yr. Tryptophan, kynurenine, and 3
      hydroxykynurenine in serum and urine were measured using LC-MS/MS. A total of 561
      RTR (age: 51 +/- 12 yr; 56% male) were included at a median of 6.0 (2.6-11.6) yr
      posttransplantation. Baseline median serum tryptophan was 40.0 (34.5-46.0)
      umol/l, serum kynurenine was 1.8 (1.4-2.2) umol/l, and serum 3-hydroxykynurenine
      was 42.2 (31.0-61.7) nmol/l. Serum kynurenine and 3-hydroxykynurenine were
      strongly associated with parameters of systemic inflammation. During follow-up
      for 7.0 (6.2-7.5) yr, 51 RTR (9%) developed graft failure and 120 RTR (21%) died.
      Both serum kynurenine and 3-hydroxykynurenine were independently associated with
      graft failure [HR 1.72 (1.23-2.41), P = 0.002; and HR 2.03 (1.42-2.90), P <
      0.001]. Serum 3-hydroxykynurenine was also independently associated with
      mortality [HR 1.37 (1.08-1.73), P = 0.01], whereas serum kynurenine was not.
      Urinary tryptophan/kynurenine pathway parameters were not associated with
      outcome. Of tryptophan metabolites, serum 3-hydroxykynurenine is cross
      sectionally most strongly and consistently associated with systemic inflammation
      and prospectively with adverse long-term outcome after kidney transplantation.
      Serum 3-hydroxykynurenine may be an interesting biomarker and target for the
      evaluation of drugs interfering in the tryptophan/kynurenine pathway.

PMID- 28490532
TI  - Podocyte-specific knockout of cyclooxygenase 2 exacerbates diabetic kidney
      disease.
AB  - Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to
      glomerular injury in diabetic kidney disease, but some basal level of podocyte
      COX2 expression might be required to promote podocyte attachment and/or survival.
      To investigate the role of podocyte COX2 expression in diabetic kidney disease,
      we deleted COX2 specifically in podocytes in a mouse model of Type 1 diabetes
      mellitus (Akita mice). Podocyte-specific knockout (KO) of COX2 did not affect
      renal morphology or albuminuria in nondiabetic mice. Albuminuria was
      significantly increased in wild-type (WT) and KO Akita mice compared with
      nondiabetic controls, and the increase in albuminuria was significantly greater
      in KO Akita mice compared with WT Akita mice at both 16 and 20 wk of age. At the
      20-wk time point, mesangial expansion was also increased in WT and KO Akita mice
      compared with nondiabetic animals, and these histologic abnormalities were not
      improved by KO of COX2. Tubular injury was seen only in diabetic mice, but there
      were no significant differences between groups. Thus, KO of COX2 enhanced
      albuminuria and did not improve the histopathologic features of diabetic kidney
      disease. These data suggest that 1) KO of COX2 in podocytes does not ameliorate
      diabetic kidney disease in Akita mice, and 2) some basal level of podocyte COX2
      expression in podocytes is necessary to attenuate the adverse effects of diabetes
      on glomerular filtration barrier function.

PMID- 28490535
TI  - Vaccines to Accelerate Malaria Elimination and Eventual Eradication.
AB  - Remarkable progress has been made in coordinated malaria control efforts with
      substantial reductions in malaria-associated deaths and morbidity achieved
      through mass administration of drugs and vector control measures including
      distribution of long-lasting insecticide-impregnated bednets and indoor residual
      spraying. However, emerging resistance poses a significant threat to the
      sustainability of these interventions. In this light, the malaria research
      community has been charged with the development of a highly efficacious vaccine
      to complement existing malaria elimination measures. As the past 40 years of
      investment in this goal attests, this is no small feat. The malaria parasite is a
      highly complex organism, exquisitely adapted for survival under hostile
      conditions within human and mosquito hosts. Here we review current vaccine
      strategies to accelerate elimination and the potential for novel and innovative
      approaches to vaccine design through a better understanding of the host-parasite
      interaction.

PMID- 28490536
TI  - The Bioenergetics of Exercise.
AB  - Animals possess a remarkable ability to perform physical activity over a wide
      range of workloads and durations, reflecting both the inherent efficiency and
      large reserve capacity of energy transfer systems. Deciphering how different
      organ/physiological systems respond to the acute and chronic demands of exercise
      depends on a foundational understanding of the redox and bioenergetic principles
      that underlie the flow of electrons in living systems and its coupling to ATP
      synthesis. The purpose of this review is to set the stage to cover (1) the
      thermodynamic driving forces responsible for generating and maintaining the
      energy charge that establishes and sustains life for cells, and (2) how cellular
      energy transfer systems respond to changes in energy demand to ensure energy
      charge is preserved.

PMID- 28490537
TI  - Adaptations to Endurance and Strength Training.
AB  - The capacity for human exercise performance can be enhanced with prolonged
      exercise training, whether it is endurance- or strength-based. The ability to
      adapt through exercise training allows individuals to perform at the height of
      their sporting event and/or maintain peak physical condition throughout the life
      span. Our continued drive to understand how to prescribe exercise to maximize
      health and/or performance outcomes means that our knowledge of the adaptations
      that occur as a result of exercise continues to evolve. This review will focus on
      current and new insights into endurance and strength-training adaptations and
      will highlight important questions that remain as far as how we adapt to
      training.

PMID- 28490539
TI  - Physiological Redundancy and the Integrative Responses to Exercise.
AB  - The biological responses to acute and chronic exercise are marked by a high level
      of physiological redundancy that operates at various levels of integration,
      including the molecular, cellular, organ-system, and whole-body scale. During
      acute exercise, this redundancy protects whole-body homeostasis in the face of 10
      fold or more increases in whole-body metabolic rate. In some cases, there are
      "trade-offs" between optimizing the performance of a given organ or system versus
      whole-body performance. Physiological redundancy also plays a key role in the
      adaptive responses to exercise training and high levels of habitual physical
      activity, including the positive effects of regular exercise on health.
      Appreciation of the general principles of physiological redundancy is critical to
      (1) gain an overall understanding of short- and long-term responses to exercise,
      and (2) place physiological responses occurring at various levels of integration
      in perspective.

PMID- 28490540
TI  - The Biology of Plasmodium vivax.
AB  - Plasmodium vivax is the second most prevalent cause of malaria worldwide and the
      leading cause of malaria outside of Africa. Although infections are seldom fatal
      clinical disease can be debilitating and imposes significant health and economic
      impacts on affected populations. Estimates of transmission and prevalence
      intensity can be problematic because many episodes of vivax originate from
      hypnozoite stages in the liver that have remained dormant from previous
      infections by an unknown mechanism. Lack of treatment options to clear
      hypnozoites and the ability to infect mosquitoes before disease symptoms present
      represent major challenges for control and eradication of vivax malaria.
      Compounding these challenges is the unique biology of P. vivax and limited
      progress in development of experimental research tools, thereby hindering
      development of new drugs and vaccines. Renewed emphasis on vivax malaria research
      is beginning to make progress in overcoming some of these challenges.

PMID- 28490538
TI  - Cellular Constituents of the Prostate Stroma: Key Contributors to Prostate Cancer
      Progression and Therapy Resistance.
AB  - Reciprocal signaling between prostate stroma and its epithelium are fundamental
      to organ development and homeostasis. Similarly, interactions between tumor cells
      and stromal constituents are central to key aspects of carcinogenesis and
      malignancy growth involving tumor cell invasion, dissemination, and growth in
      distant sites. The prostate stroma is complex with several distinct resident cell
      types, infiltrating nonresident cell types and an amalgam of structural matrix
      factors, matricellular proteins, metabolites, growth factors, and cytokines. Of
      importance, the stroma is dynamic with changes in composition as a cause or
      consequence of intrinsic and extrinsic factors. In the context of epithelial
      neoplasia, the prostate stroma undergoes phenotypic changes with a loss of well
      differentiated smooth muscle cell population and the expansion of cancer
      associated fibroblast populations. This reactive stroma further coevolves with
      tumor progression. Recent studies show the role of tumor microenvironment
      components in therapy resistance and highlight the importance of a thorough
      knowledge of cross talk between tumor cells and microenvironment niches to
      develop new therapeutic strategies.

PMID- 28490541
TI  - Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise.
AB  - Habitual endurance exercise training is associated with multisystemic metabolic
      adaptations that lower the risk of inactivity-associated disorders such as
      obesity and type 2 diabetes mellitus (T2DM). Identification of complex systemic
      signaling networks responsible for these benefits are of great interest because
      of their therapeutic potential in metabolic diseases; however, specific signals
      that modulate the multisystemic benefits of exercise in multiple tissues and
      organs are only recently being discovered. Accumulated evidence suggests that
      muscle and other tissues have an endocrine function and release peptides and
      nucleic acids into the circulation in response to acute endurance exercise to
      mediate the multisystemic adaptations. Factors released from skeletal muscle have
      been termed myokines and we propose that the total of all factors released in
      response to endurance exercise (including peptides, nucleic acids, and
      metabolites) be termed, "exerkines." We propose that many of the exerkines are
      released within extracellular vesicles called exosomes, which regulate peripheral
      organ cross talk. Exosomes (30-140 nm) and larger microvesicles [MVs] (100-1000
      nm) are subcategories of extracellular vesicles that are released into the
      circulation. Exosomes contain peptides and several nucleic acids (microRNA
      [miRNA], messenger RNA [mRNA], mitochondrial DNA [mtDNA]) and are involved in
      intercellular/tissue exchange of their contents. An acute bout of endurance
      exercise increases circulating exosomes that are hypothesized to mediate organ
      cross talk to promote systemic adaptation to endurance exercise. Further support
      for the role of exosomes (and possibly MVs) in mediating the systemic benefits of
      exercise comes from the fact that the majority of the previously reported
      myokines/exerkines are found in extracellular vesicles databases (Vesiclepedia
      and ExoCarta). We propose that exosomes isolated from athletes following exercise
      or exosomes bioengineered to incorporate one or many of known exerkines will be
      therapeutically useful in the treatment of obesity, T2DM, and other aging
      associated metabolic disorders.

PMID- 28490542
TI  - Evolution of Premalignant Disease.
AB  - Where does cancer come from? Although the cell-of-origin is difficult to
      pinpoint, cancer clones harbor information about their clonal ancestries. In an
      effort to find cells before they evolve into a life-threatening cancer,
      physicians currently diagnose premalignant diseases at frequencies that
      substantially exceed those of clinical cancers. Cancer risk prediction relies on
      our ability to distinguish between which premalignant features will lead to
      cancer mortality and which are characteristic of inconsequential disease. Here,
      we review the evolution of cancer from premalignant disease, and discuss the
      concept that even phenotypically normal cell progenies inherently gain more
      malignant potential with age. We describe the hurdles of prognosticating cancer
      risk in premalignant disease by making reference to the underlying continuous and
      multivariate natures of genotypes and phenotypes and the particular challenge
      inherent in defining a cell lineage as "cancerized."

PMID- 28490544
TI  - Does India really not have enough money to spend on healthcare?

PMID- 28490543
TI  - Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy.
AB  - Skeletal muscle hypertrophy is a widely sought exercise adaptation to counteract
      the muscle atrophy of aging and disease, or to improve athletic performance.
      While this desired muscle enlargement is a well-known adaptation to resistance
      exercise training (RT), the mechanistic underpinnings are not fully understood.
      The purpose of this review is thus to provide the reader with a summary of recent
      advances in molecular mechanisms-based on the most current literature-that are
      thought to promote RT-induced muscle hypertrophy. We have therefore focused this
      discussion on the following areas of fertile investigation: ribosomal function
      and biogenesis, muscle stem (satellite) cell activity, transcriptional
      regulation, mechanotransduction, and myokine signaling.

PMID- 28490545
TI  - Red blood cell distribution width and myocardial scar burden in coronary artery
      disease.
AB  - INTRODUCTION: Red blood cell distribution width (RDW) is a novel independent
      marker of cardiovascular disease including heart failure, coronary artery disease
      and myocardial ischaemia. The aim of the study was to investigate a possible
      relationship between RDW and myocardial scar burden, as assessed by a MIBI
      viability scan. A secondary objective was to assess whether there is an
      association between RDW and left ventricular ejection fraction (LVEF). METHODS:
      The study comprised 123 subjects with ischaemic heart disease who underwent a
      myocardial viability scan between June 2008 and July 2014. Haemoglobin, mean
      corpuscular volume, RDW, platelet count, mean platelet volume (MPV), estimated
      glomerular filtration rate, fasting blood glucose, liver and lipid profiles were
      evaluated for all patients. The extent of myocardial scarring and LVEF were
      noted. Data were analysed using IBM SPSS Statistics 22.0. Univariate followed by
      multivariate analyses were performed to assess for independent predictors of
      myocardial scarring and LVEF, respectively. RESULTS: The mean age of the study
      population was 63.5 years; most of the subjects were men. The median LVEF was 31%
      and median percentage of myocardial scarring was 8.7%. Multivariate analyses
      revealed that RDW, HDL-cholesterol and alanine transaminase were independent
      predictors of myocardial scarring while RDW, MPV, LDL-cholesterol and gamma
      glutamyl transpeptidase were independent predictors of LVEF. CONCLUSIONS:
      Increased RDW is an independent predictor both of myocardial scar burden and of
      impaired left ventricular function in subjects with coronary artery disease.

PMID- 28490546
TI  - A multicentre evaluation of an opioid patient-provider agreement.
AB  - The role of the patient-provider agreement (PPA) is to set forth respective roles
      and responsibilities for opioid therapy with the goal of improving outcomes,
      reducing risks, and improving patient education. The Food and Drug Administration
      (FDA) Safe Use Initiative Opioid PPA Working Group convened to develop a PPA and
      test it for acceptability as an educational and shared decision-making tool in
      opioid therapy. This multicentre study evaluated the utility of the PPA, how
      readily patients understood it, its ability to educate patients in an unbiased
      way about opioid treatment and the feasibility of incorporating a PPA in clinical
      practice. A total of 117 patients and 14 providers at urban centres were included
      (mean patient age: 56 years) with 85% of patients treated for pain for >3 months.
      Most patients reported the PPA to be 'somewhat helpful' or 'very helpful' in
      deciding a course of treatment (96%) and 'easy to understand' (97%). Both
      patients and prescribers (89% and 92%, respectively) found the PPA was neutral in
      terms of presenting opioid therapy. Most centres found the PPA could be
      administered in <=10 min and 72% of prescribers said this PPA could be readily
      incorporated into their practice. This PPA was perceived by both patients and
      prescribers as helpful in deciding a course of treatment and unbiased in terms of
      presentation of the risks and benefits of opioid therapy.

PMID- 28490547
TI  - Board certification in Japan: corruption and near-collapse of reform.

PMID- 28490549
TI  - Possible relationship between general and pregnancy-related anxiety during the
      first half of pregnancy and the birth process: a prospective cohort study.
AB  - OBJECTIVES: The rate of interventions during childbirth has increased
      dramatically during the last decades. Maternal anxiety might play a role in the
      progress of the labour process and interventions during labour. This study aimed
      to identify associations between anxiety in the first half of pregnancy and the
      birth process, including any interventions required during labour. In addition,
      differences in the associations by parity and ethnicity were explored. DESIGN:
      Prospective cohort study. SETTING: Primary care midwifery practices and
      secondary/tertiary care obstetric practices in Amsterdam, participating in the
      multiethnic ABCD (Amsterdam Born Children and their Development) study
      (participation rate 96%; response 8266/12 373 (67%)). PARTICIPANTS: Included were
      women with singletons, alive at labour start, with a gestational age >=24 weeks
      (n=6443). INDEPENDENT VARIABLE: General anxiety (State-Trait Anxiety Inventory
      state) and pregnancy-related anxiety (Pregnancy-Related Anxieties Questionnaire
      (PRAQ)) were self-reported in the first half of pregnancy. OUTCOMES: Associations
      between both forms of anxiety and several indicators of the birth process were
      analysed. Subgroup analyses were performed for parity and ethnicity. RESULTS: The
      prevalence of high general anxiety (State-Trait Anxiety Inventory score >=43) and
      pregnancy-related anxiety (PRAQ score >=P90) were 30.9% and 11.0%, respectively.
      After adjustment, in nulliparae, both general anxiety and pregnancy-related
      anxiety were associated with pain relief and/or sedation (OR for general anxiety
      1.23; 95% CI 1.02 to 1.48; OR for pregnancy-related anxiety 1.45; 95% CI 1.14 to
      1.85). In multiparae, general anxiety was associated with induction of labour (OR
      1.53; 95% CI 1.16 to 2.03) and pregnancy-related anxiety was associated with
      primary caesarean section (OR 1.66; 95% CI 1.02 to 2.70). Associations were
      largely similar for all ethnicities. CONCLUSIONS: High levels of general and
      pregnancy-related anxiety in early pregnancy contribute modestly to more
      interventions during the birth process with similar associations between ethnic
      groups, but with some differences between nulliparae and multiparae.

PMID- 28490550
TI  - Multimorbidity as an important issue among women: results of a gender difference
      investigation in a large population-based cross-sectional study in West Asia.
AB  - OBJECTIVES: To investigate the impact of gender on multimorbidity in northern
      Iran. DESIGN: A cross-sectional analysis of the Golestan cohort data. SETTING:
      Golestan Province, Iran. STUDY POPULATION: 49 946 residents (age 40-75 years) of
      Golestan Province, Iran. MAIN OUTCOME MEASURES: Researchers collected data
      related to multimorbidity, defined as co-existence of two or more chronic
      diseases in an individual, at the beginning of a representative cohort study
      which recruited its participants from 2004 to 2008. The researchers utilised
      simple and multiple Poisson regression models with robust variances to examine
      the simultaneous effects of multiple factors. RESULTS: Women had a 25.0%
      prevalence of multimorbidity, whereas men had a 13.4% prevalence (p<0.001). Women
      of all age-groups had a higher prevalence of multimorbidity. Of note,
      multimorbidity began at a lower age (40-49 years) in women (17.3%) compared with
      men (8.6%) of the same age (p<0.001). This study identified significant
      interactions between gender as well as socioeconomic status, ethnicity, physical
      activity, marital status, education level and smoking (p<0.01). CONCLUSION:
      Prevention and control of multimorbidity requires health promotion programmes to
      increase public awareness about the modifiable risk factors, particularly among
      women.

PMID- 28490551
TI  - Selective impact of disease on short-term and long-term components of self
      reported memory: a population-based HUNT study.
AB  - BACKGROUND: Subjective memory is commonly considered to be a unidimensional
      measure. However, theories of performance-based memory suggest that subjective
      memory could be divided into more than one dimension. OBJECTIVE: To divide
      subjective memory into theoretically related components of memory and explore the
      relationship to disease. METHODS: In this study, various aspects of self-reported
      memory were studied with respect to demographics and diseases in the third wave
      of the HUNT epidemiological study in middle Norway. The study included all
      individuals 55 years of age or older, who responded to a nine-item questionnaire
      on subjective memory and questionnaires on health (n=18 633). RESULTS: A
      principle component analysis of the memory items resulted in two memory
      components; the criterion used was an eigenvalue above 1, which accounted for 54%
      of the total variance. The components were interpreted as long-term memory (LTM;
      the first component; 43% of the total variance) and short-term memory (STM; the
      second component; 11% of the total variance). Memory impairment was significantly
      related to all diseases (except Bechterew's disease), most strongly to brain
      infarction, heart failure, diabetes, cancer, chronic obstructive pulmonary
      disease and whiplash. For most diseases, the STM component was more affected than
      the LTM component; however, in cancer, the opposite pattern was seen.
      CONCLUSIONS: Subjective memory impairment as measured in HUNT contained two
      components, which were differentially associated with diseases.

PMID- 28490552
TI  - Coffee, including caffeinated and decaffeinated coffee, and the risk of
      hepatocellular carcinoma: a systematic review and dose-response meta-analysis.
AB  - OBJECTIVES: To examine the association between coffee, including caffeinated and
      decaffeinated coffee, with hepatocellular carcinoma (HCC) and assess the
      influence of HCC aetiology and pre-existing liver disease. DESIGN: We performed a
      systematic review and meta-analysis. We calculated relative risks (RRs) of HCC
      according to caffeinated and decaffeinated coffee consumption using a random
      effects dose-response meta-analysis. We tested for modification of the effect
      estimate by HCC aetiology and pre-existing liver disease. We judged the quality
      of evidence using the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) criteria. RESULTS: We found 18 cohorts, involving 2 272 642
      participants and 2905 cases, and 8 case-control studies, involving 1825 cases and
      4652 controls. An extra two cups per day of coffee was associated with a 35%
      reduction in the risk of HCC (RR 0.65, 95% CI 0.59 to 0.72). The inverse
      association was weaker for cohorts (RR 0.71, 95% CI 0.65 to 0.77), which were
      generally of higher quality than case-control studies (RR 0.53, 95% CI 0.41 to
      0.69). There was evidence that the association was not significantly altered by
      stage of liver disease or the presence/absence of high alcohol consumption, high
      body mass index, type 2 diabetes mellitus, smoking, or hepatitis B and C viruses.
      An extra two cups of caffeinated and decaffeinated coffee (2 and 3 cohort
      studies, respectively) were associated with reductions of 27% (RR 0.73, 95% CI
      0.63 to 0.85) and 14% (RR 0.86, 95% CI 0.74 to 1.00) in the risk of HCC. However,
      due to a lack of randomised controlled trials, potential publication bias and
      there being no accepted definition of coffee, the quality of evidence under the
      GRADE criteria was 'very low'. CONCLUSIONS: Increased consumption of caffeinated
      coffee and, to a lesser extent, decaffeinated coffee are associated with reduced
      risk of HCC, including in pre-existing liver disease. These findings are
      important given the increasing incidence of HCC globally and its poor prognosis.

PMID- 28490553
TI  - Using a patient decision aid for insulin initiation in patients with type 2
      diabetes: a qualitative analysis of doctor-patient conversations in primary care
      consultations in Malaysia.
AB  - OBJECTIVE: To investigate whether the use of apatient decision aid (PDA) for
      insulin initiation fulfils its purpose of facilitating patient-centred decision
      making through identifying how doctors and patients interact when using the PDA
      during primary care consultations. DESIGN: Conversation analysis of seven single
      cases of audio-recorded/video-recorded consultations between doctors and patients
      with type 2 diabetes, using a PDA on starting insulin. SETTING: Primary care in
      three healthcare settings: (1) one private clinic; (2) two public community
      clinics and (3) one primary care clinic in a public university hospital, in
      Negeri Sembilan and the Klang Valley in Malaysia. PARTICIPANTS: Clinicians and
      seven patients with type 2 diabetes to whom insulin had been recommended.
      Purposive sampling was used to select a sample high in variance across healthcare
      settings, participant demographics and perspectives on insulin. PRIMARY OUTCOME
      MEASURES: Interaction between doctors and patients in a clinical consultation
      involving the use of a PDA about starting insulin. RESULTS: Doctors brought the
      PDA into the conversation mainly by asking information-focused 'yes/no'
      questions, and used the PDA for information exchange only if patients said they
      had not read it. While their contributions were limited by doctors' questions,
      some patients disclosed issues or concerns. Although doctors' PDA-related
      questions acted as a presequence to deliberation on starting insulin, their
      interactional practices raised questions on whether patients were informed and
      their preferences prioritised. CONCLUSIONS: Interactional practices can hinder
      effective PDA implementation, with habits from ordinary conversation potentially
      influencing doctors' practices and complicating their implementation of patient
      centred decision-making. Effective interaction should therefore be emphasised in
      the design and delivery of PDAs and in training clinicians to use them.

PMID- 28490554
TI  - Feasibility cluster randomised controlled trial of a within-consultation
      intervention to reduce antibiotic prescribing for children presenting to primary
      care with acute respiratory tract infection and cough.
AB  - OBJECTIVE: To investigate recruitment and retention, data collection methods and
      the acceptability of a 'within-consultation' complex intervention designed to
      reduce antibiotic prescribing. DESIGN: Primary care feasibility cluster
      randomised controlled trial. SETTING: 32 general practices in South West England
      recruiting children from October 2014 to April 2015. PARTICIPANTS: Children (aged
      3 months to <12 years) with acute cough and respiratory tract infection (RTI).
      INTERVENTION: A web-based clinician-focussed clinical rule to predict risk of
      future hospitalisation and a printed leaflet with individualised child health
      information for carers, safety-netting advice and a treatment decision record.
      CONTROLS: Usual practice, with clinicians recording data on symptoms, signs and
      treatment decisions. RESULTS: Of 542 children invited, 501 (92.4%) consented to
      participate, a month ahead of schedule. Antibiotic prescribing data were
      collected for all children, follow-up data for 495 (98.8%) and the National
      Health Service resource use data for 494 (98.6%). The overall antibiotic
      prescribing rates for children's RTIs were 25% and 15.8% (p=0.018) in
      intervention and control groups, respectively. We found evidence of
      postrandomisation differential recruitment: the number of children recruited to
      the intervention arm was higher (292 vs 209); over half were recruited by
      prescribing nurses compared with less than a third in the control arm; children
      in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03)
      and appeared to be more unwell than those in the control arm with higher
      respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness
      severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews
      with clinicians confirmed preferential recruitment of less unwell children to the
      trial, more so in the control arm. CONCLUSION: Differential recruitment may
      explain the paradoxical antibiotic prescribing rates. Future cluster level
      studies should consider designs which remove the need for individual consent
      postrandomisation and embed the intervention within electronic primary care
      records. TRIAL REGISTRATION NUMBER: ISRCTN 23547970 UKCRN STUDY ID: 16891.

PMID- 28490555
TI  - Telehealthcare for patients suffering from chronic obstructive pulmonary disease:
      effects on health-related quality of life: results from the Danish 'TeleCare
      North' cluster-randomised trial.
AB  - OBJECTIVE: To assess the effect of telehealthcare compared with usual practice in
      patients with chronic obstructive pulmonary disease (COPD). DESIGN: A cluster
      randomised trial with 26 municipal districts that were randomly assigned either
      to an intervention group whose members received telehealthcare in addition to
      usual practice or to a control group whose members received usual practice only
      (13 districts in each arm). SETTING: Twenty-six municipal districts in the North
      Denmark Region of Denmark. PARTICIPANTS: Patients who fulfilled the Global
      Initiative for COPD guidelines and one of the following criteria: COPD Assessment
      Test score >=10; or Medical Research Dyspnoea Council Scale >=3; or Modified
      Medical Research Dyspnoea Council Scale >=2; or >=2 exacerbations during the past
      12 months. MAIN OUTCOME MEASURES: Health-related quality of life (HRQoL) assessed
      by the physical component summary (PCS) and mental component summary (MCS) scores
      of the Short Form 36-Item Health Survey, Version 2. Data were collected at
      baseline and at 12 month follow-up and analysed according to the intention-to
      treat principle with complete cases, n=574 (258 interventions; 316 controls) and
      imputed data, n=1225 (578 interventions, 647 controls) using multilevel
      modelling. RESULTS: In the intention-to-treat analysis (n=1225), the raw mean
      difference in PCS from baseline to 12 month follow-up was -2.6 (SD 12.4) in the
      telehealthcare group and -2.8 (SD 11.9) in the usual practice group. The raw mean
      difference in MCS scores in the same period was -4.7 (SD 16.5) and -5.3 (SD 15.5)
      for telehealthcare and usual practice, respectively. The adjusted mean difference
      in PCS and MCS between groups at 12 months was 0.1 (95% CI -1.4 to 1.7) and 0.4
      (95% CI -1.7 to 2.4), respectively. CONCLUSIONS: The overall sample and all
      subgroups demonstrated no statistically significant differences in HRQoL between
      telehealthcare and usual practice. TRIAL REGISTRATION NUMBER: NCT01984840;
      Results.

PMID- 28490556
TI  - Maternal alcohol disorders and school achievement: a population cohort record
      linkage study in Western Australia.
AB  - OBJECTIVE: Maternal alcohol use disorder is a risk factor for a range of
      developmental outcomes in children. This study examines school achievement in
      children of Indigenous and non-Indigenous mothers with an alcohol-related
      diagnosis. DESIGN, SETTING AND PARTICIPANTS: This is a Western Australian
      population cohort study of mothers with a record of an alcohol-related diagnosis
      classified by the International Classification of Diseases Revisions 9/10 codes
      as recorded on administrative databases, and of their offspring born between 1989
      and 2007 (n=18 486 exposed children), with a frequency matched comparison cohort
      of mothers with no record of alcohol diagnosis and their offspring (n=48 262
      comparison children). OUTCOMES: Records were linked with school achievement data
      for numeracy and literacy from Years 3, 5, 7 and 9 (age range: ~8-14 years) based
      on statewide and national testing. Mixed multivariate models with a random
      intercept per child were used to assess the relationship between exposure and the
      timing of exposure with failure to meet minimum standardised benchmarks. RESULTS:
      Academic achievement was lower in all testing domains (reading, writing, spelling
      and numeracy) among children of mothers with an alcohol diagnosis and persisted
      across all year groups examined. The highest ORs at Year 9 for non-Indigenous
      children were in reading (adjusted OR (aOR) 1.6, 95% CI 1.4 to 1.8) and in
      writing for Indigenous children (aOR 2.0, 95% CI 1.8 to 2.3). CONCLUSION:
      Children of mothers with alcohol use disorders are at risk of not meeting minimum
      educational benchmarks in numeracy and literacy, with the risk highest among
      Indigenous children.

PMID- 28490557
TI  - The effect of empagliflozin on oxidative nucleic acid modifications in patients
      with type 2 diabetes: protocol for a randomised, double-blinded, placebo
      controlled trial.
AB  - INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and
      mortality in patients with type 2 diabetes (T2D). Although glycaemic control
      reduces microvascular complications, the effect of intensive treatment strategies
      or individual drugs on macrovascular diseases is still debated. RNA oxidation is
      associated with increased mortality in patients with T2D. Inspired by animal
      studies showing effect of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor
      (empagliflozin) on oxidative stress and a recent trial evaluating empagliflozin
      that demonstrated improved cardiovascular outcomes in patients with T2D at high
      risk of cardiovascular events, we hypothesise that empagliflozin lowers oxidative
      stress. METHODS AND ANALYSIS: In this randomised, double-blinded and placebo
      controlled study, 34 adult males with T2D will be randomised (1:1) to
      empagliflozin or placebo once daily for 14 days as add-on to ongoing therapy. The
      primary endpoints will be changes in 24-hour urinary excretion of 8-oxo-7,8
      dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
      determined before and after intervention (by ultra-performance liquid
      chromatography tandem mass-spectrometry). Additionally, fasting levels of
      malondialdehyde (MDA) will be determined in plasma before and after intervention
      (by high-performance liquid chromatography). Further, the plasma levels of iron,
      transferrin, transferrin-saturation, and ferritin are determined to correlate the
      iron metabolism to the markers of oxidative modifications. ETHICS AND
      DISSEMINATION: The study protocol has been approved by the Regional Committee on
      Biomedical Research Ethics (approval number H-16017433), the Danish Medicines
      Agency, and the Danish Data Protection Agency, and will be carried out under the
      surveillance and guidance of the GCP unit at Bispebjerg Frederiksberg Hospital,
      University of Copenhagen in compliance with the ICH-GCP guidelines and in
      accordance with the Declaration of Helsinki. The results of this study will be
      presented at national and international conferences, and submitted to a peer
      reviewed international journal with authorship in accordance with Internation
      Committee of Medical Journal Editors (ICMJE) Recommendations state. TRIAL
      REGISTRATION: Study name: EMPOX; Pre-results: clinicaltrials.gov (NCT02890745).
      Protocol version 5.1 - August, 2016.

PMID- 28490558
TI  - Health status and needs of cancer survivors attending the Sydney Survivorship
      Centre clinics and programmes: a protocol for longitudinal evaluation of the
      centre's services.
AB  - INTRODUCTION: The care of cancer survivors after primary adjuvant treatment is
      recognised as a distinct phase of the cancer journey. Recent research highlights
      the importance of lifestyle factors in treating symptoms, potentially decreasing
      risk of a cancer recurrence and modifying the risk of developing other chronic
      illnesses that are increased in the cancer population. Survivorship services aim
      to deliver care that addresses these issues. The overall aims are to determine
      the health status of cancer survivors and to evaluate the services offered by the
      Sydney Survivorship Centre (SSC). METHODS AND ANALYSIS: This is an observational
      single-centre study evaluating the longitudinal physical and psychological
      health, symptoms, quality of life and lifestyle (physical activity and nutrition)
      of early stage cancer survivors attending the multidisciplinary Sydney
      Survivorship Clinic and survivors (at any stage of the cancer journey) and
      caregivers participating in SSC courses. Evaluation of patient satisfaction is
      included. Patient-reported outcomes and patient characteristics will be
      summarised using descriptive statistics with Spearman rank sum correlation
      coefficients to determine associations between patient-reported outcomes.
      Regression modelling may be used to further evaluate associations and to
      investigate risk factors and predictors of health outcomes. Qualitative data will
      be analysed using thematic analysis to identify themes. Sample size will be
      determined by attendance of consenting patients at clinics and courses. ETHICS
      AND DISSEMINATION: The study has received ethics approval from the Concord
      Repatriation General Hospital Human Research Ethics Committee (HREC/14/CRGH/23).
      The results will be published and presented at appropriate conferences.This study
      will provide important information regarding the health status and needs of
      Australian cancer survivors and the ability of the survivorship centre to address
      these needs. These data will shape the future direction of survivorship care in
      Australia and facilitate the design of interventions or measures to provide
      better quality of care to this patient population.

PMID- 28490559
TI  - Screening for coronary artery disease in patients with type 2 diabetes: a meta
      analysis and trial sequential analysis.
AB  - OBJECTIVE: To evaluate the efficacy of coronary artery disease screening in
      asymptomatic patients with type 2 diabetes and assess the statistical reliability
      of the findings. METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Library
      and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled
      trials evaluating coronary artery disease screening in asymptomatic patients with
      type 2 diabetes and reporting cardiovascular events and/or mortality were
      included. Data were summarised with Mantel-Haenszel relative risk. Trial
      sequential analysis (TSA) was used to evaluate the optimal sample size to detect
      a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac
      events (non-fatal myocardial infarction and cardiovascular death); secondary
      outcomes were non-fatal myocardial infarction, myocardial revascularisations and
      heart failure. RESULTS: One hundred thirty-five references were identified and 5
      studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all
      cause deaths and 100 cardiac events. Screening for coronary artery disease was
      not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to
      1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility
      boundaries were reached for all-cause mortality and a relative risk reduction of
      40% between treatments could be discarded. However, there is not enough
      information for firm conclusions for cardiac events. For secondary outcomes no
      benefit or harm was identified; optimal sample sizes were not reached.
      CONCLUSION: Current available data do not support screening for coronary artery
      disease in patients with type 2 diabetes for preventing fatal events. Further
      studies are needed to assess the effects on cardiac events. PROSPERO:
      CRD42015026627.

PMID- 28490560
TI  - Nursing home team-care deprescribing study: a stepped-wedge randomised controlled
      trial protocol.
AB  - INTRODUCTION: An ageing population has become an urgent concern for Asia in
      recent times. In nursing homes, polypharmacy has also become a compounding issue.
      Deprescribing practice is an evidence-based strategy to provide a better outcome
      in this group of patients; however, its implementation in nursing homes is often
      challenging, and prospective outcome data on deprescribing practice in the
      elderly is lacking. Our study assesses the implementation of team-care
      deprescribing to understand the benefits of this practice in geriatric setting
      and to explore the factors affecting deprescribing practice. METHODS AND
      ANALYSIS: This multicentre prospective study consists of a prestudy interview
      questionnaire, and a preintervention and postintervention study to be conducted
      in the nursing home setting on residents at least 65 years old and on five or
      more medications. We will employ a cluster randomised stepped-wedge
      interventional design, based on a five-step (reviewing, checking, discussion,
      communication and documentation) team-care deprescribing practice coupled with
      the use of a deprescribing guide (consisting of Beers and STOPP criteria, as well
      as drug interaction checking), to assess the health and pharmacoeconomic outcome
      in nursing homes' practice. Primary outcome measures of the intervention will
      consist of fall risks using a fall risk assessment tool. Other outcomes assessed
      include fall rates, pill burden including number of pills per day, number of
      doses per day and number of medications prescribed. Cost-related measures will
      include the use of cost-benefit analysis, which is calculated from the medication
      cost savings from deprescribing. For the prestudy interview questionnaire,
      findings will be analysed qualitatively using thematic analysis. ETHICS AND
      DISSEMINATION: This study is approved by the Domain Specific Review Board of
      National Healthcare Group, Singapore (2016/00422) and Monash University Human
      Research Ethics Committee (2016-1430-7791). The study findings shall be
      disseminated in international conferences and peer-reviewed publications. The
      study is registered with ClinicalTrials.gov (NCT02863341), Pre-results.

PMID- 28490561
TI  - Four-year nationwide incidence of retinitis pigmentosa in South Korea: a
      population-based retrospective study from 2011 to 2014.
AB  - OBJECTIVE: To determine the incidence of retinitis pigmentosa (RP) in South
      Korea. DESIGN: Nationwide, population-based retrospective study. SETTING: Census
      population of South Korea PARTICIPANTS: This study involved the entire population
      of South Korea (n=47 990 761). Patients confirmed as having RP by an
      ophthalmologist from 1 January 2011 to 31 December 2014 were included. PRIMARY
      OUTCOME MEASURE: The average incidence of RP during the 4-year study period was
      estimated using population data from the 2010 Korean census. RESULTS: A total of
      3144 (1567 men and 1577 women) patients confirmed as having RP were identified.
      The average incidence of RP was 1.64 cases/100 000 person-years (95% CI 1.58 to
      1.70). The incidence of RP distribution skewed to the left across age groups,
      with one smaller peak observed in the 20-24-year-old age group (1.24 cases/100
      000 person-years) and a larger peak observed in the 65-69-year-old age group
      (3.26 cases/100 000 person-years). The overall incidence was similar in men and
      women (1.64 cases/100 000 person-years (95% CI 1.56 to 1.73) for men; 1.63
      cases/100 000 person-years (95% CI 1.55 to 1.72) for women). CONCLUSIONS: Our
      study's estimates of the nationwide population-based incidence of RP in an Asian
      population will help advance the understanding of the disease onset and allow
      healthcare systems to plan accordingly.

PMID- 28490562
TI  - Autism spectrum disorder: updated prevalence and comparison of two birth cohorts
      in a nationally representative Australian sample.
AB  - OBJECTIVES: This study aimed to (1) provide an update on the prevalence of parent
      reported autism spectrum disorder (ASD) diagnosis and new information about
      teacher-reported ASD in two nationally representative Australian cohorts at ages
      10-11 years, (2) examine differences in cohort demographic and clinical profiles
      and (3) compare the prevalence of teacher-reported ASD and any changes in
      categorisation over time across the cohorts. DESIGN: Secondary analyses were
      undertaken using data from the Longitudinal Study of Australian Children (LSAC).
      PARTICIPANTS: Children were recruited at kindergarten age (K cohort; birth year
      1999/2000) and birth (B cohort; birth year 2003/2004), with follow-up of every 2 
      years for six waves. PRIMARY OUTCOME MEASURES: Parent-reported and teacher
      reported ASD diagnosis was ascertained at three time points (waves 4-6). RESULTS:
      At age 10-11 years, the adjusted prevalence of parent-reported ASD diagnosis was
      3.9% (95% CI 3.2 to 4.5) and 2.4% (95% CI 1.6 to 2.9) in the B and K cohorts,
      respectively. Teacher-reported prevalence of ASD was 1.7% (95% CI 1.2 to 2.1) in
      the B cohort and 0.9% (95% CI 0.56 to 1.14) in the K cohort. Parents reported
      fewer conduct and peer problems and teachers more pro-social behaviour in B
      relative to K cohort ASD children. Children reported only by parents in the later
      born B cohort had milder behaviour problems than parent-agreed and teacher-agreed
      cases. Although individual switching to ASD from other categories from 8-9 to 10
      11 years was low (K cohort n=5, B cohort n=6), teachers reported more children
      with ASD in the B than K cohort at 10-11 years and fewer children with emotional/
      behavioural problems. CONCLUSIONS: The higher prevalence of parent-reported and
      teacher-reported ASD diagnosis in the later-born cohort may be partially
      explained by identifying children with milder behavioural problems as ASD and a
      change in the use of diagnostic categories in schools.

PMID- 28490563
TI  - Are medical outliers associated with worse patient outcomes? A retrospective
      study within a regional NHS hospital using routine data.
AB  - OBJECTIVE: To explore the quality and safety of patients' healthcare provision by
      identifying whether being a medical outlier is associated with worse patient
      outcomes. A medical outlier is a hospital inpatient who is classified as a
      medical patient for an episode within a spell of care and has at least one non
      medical ward placement within that spell. DATA SOURCES: Secondary data from the
      Patient Administration System of a district general hospital were provided for
      the financial years 2013/2014-2015/2016. The data included 71 038 medical patient
      spells for the 3-year period. STUDY DESIGN: This research was based on a
      retrospective, cross-sectional observational study design. Multivariate logistic
      regression and zero-truncated negative binomial regression were used to explore
      patient outcomes (in-hospital mortality, 30-day mortality, readmissions and
      length of stay (LOS)) while adjusting for several confounding factors. PRINCIPAL
      FINDINGS: Univariate analysis indicated that an outlying medical in-hospital
      patient has higher odds for readmission, double the odds of staying longer in the
      hospital but no significant difference in the odds of in-hospital and 30-day
      mortality. Multivariable analysis indicates that being a medical outlier does not
      affect mortality outcomes or readmission, but it does prolong LOS in the
      hospital. CONCLUSIONS: After adjusting for other factors, medical outliers are
      associated with an increased LOS while mortality or readmissions are not worse
      than patients treated in appropriate specialty wards. This is in line with
      existing but limited literature that such patients experience worse patient
      outcomes. Hospitals may need to revisit their policies regarding outlying
      patients as increased LOS is associated with an increased likelihood of harm
      events, worse quality of care and increased healthcare costs.

PMID- 28490564
TI  - Association between serum osmolarity and mortality in patients who are critically
      ill: a retrospective cohort study.
AB  - OBJECTIVES: This research aims to explore the association between serum
      osmolarity and mortality in patients who are critically ill with specific
      categories of disease. DESIGN: A retrospective cohort study. SETTING AND
      PARTICIPANTS: Data were extracted from an online database named 'Multiparameter
      Intelligent Monitoring in Intensive Care II'. 16 598 patients were included.
      METHODS: Patients were divided into six disease subgroups based on the diagnosis
      at admission: cardiac, cerebral, vascular, gastrointestinal, respiratory and non
      respiratory. The association between maximum osmolarity (osmolaritymax) and
      hospital mortality in each subgroup was evaluated using osmolaritymax as a design
      variable (six levels). RESULTS: Analysis of the 16 598 patients revealed a 'U'
      shaped relationship between osmolarity and mortality with a threshold of 300
      mmoL/L. For patients with non-respiratory disease, both hypo-osmolarity and
      hyperosmolaritymax were associated with increased mortality, with the OR
      increasing from osmolaritymax level 3 (OR: 1.98, 95% CI 1.69 to 2.33, p<0.001) to
      level 6 (OR: 4.45, 95% CI 3.58 to 5.53, p<0.001), using level 2 (290-309 mmoL/L)
      as the reference group. For patients with respiratory disease, however, neither
      hypo-osmolarity nor hyperosmolaritymax was significantly associated with
      mortality (levels 1 to 5) except for extreme hyperosmolaritymax (>=340 mmoL/L,
      OR: 2.03, 95% CI 1.20 to 3.42, p=0.007). ORs of mortality in the other four
      subgroups (cardiac, cerebral, vascular, gastrointestinal) were similar, with OR
      progressively increasing from level 3 to 6. In all six subgroups, vasopressin use
      was consistently associated with increased mortality. CONCLUSIONS:
      Hyperosmolarity is associated with increased mortality in patients who are
      critically ill with cardiac, cerebral, vascular and gastrointestinal admission
      diagnoses, with thresholds at 300 mmoL/L. For patients with respiratory disease,
      however, no significant association was detected.

PMID- 28490565
TI  - Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in
      patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4
      inhibitors in Japan: a study protocol for a prospective, multicentre, blinded
      endpoint phase IV randomised controlled trial (PRIME-V study).
AB  - INTRODUCTION: In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently
      used as the treatment of choice for patients with type 2 diabetes. In some cases,
      however, poor glycaemic and body weight control issues persist despite treatment
      with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent
      glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and
      body weight in patients with type 2 diabetes. However, further investigation
      regarding the effects of SGLT-2 inhibitors on body composition, especially in the
      Asian population who tends to have relatively low-to-moderate body mass indices,
      is required. Therefore, we aim to determine the effects of treatment with SGLT-2
      inhibitors or metformin for reducing visceral fat in 106 Asian patients with type
      2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50
      mg daily) for poor glycaemic control. METHODS AND ANALYSIS: A prospective,
      multicentre, blinded-endpoint phase IV randomised controlled study will be
      conducted to evaluate the safety and efficacy of a 24-week treatment with either
      an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and
      plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the
      eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg
      daily) or metformin (1000 mg daily). The primary outcome is the rate of change in
      the total area of visceral fat for patients in both treatment groups, measured
      using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical
      information, will perform centralised analysis of the images in a unified
      measurement condition. ETHICS AND DISSEMINATION: The protocol was approved by the
      institutional review board of each hospital. This study is ongoing and due to
      finish in April 2017. The findings of this study will be disseminated via peer
      reviewed publications and conference presentations, and will also be disseminated
      to participants. TRIAL REGISTRATION NUMBER: UMIN000015170, R000016861
      (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000016861); Pre
      results.

PMID- 28490566
TI  - A retrospective cohort study of the utility of the modified early warning score
      for interfacility transfer of patients with traumatic injury.
AB  - OBJECTIVE: The modified early warning score (MEWS) is a 'track and trigger' score
      using routine physiological vital signs. The objective is to determine if the
      pretransfer MEWS can be used for predicting outcomes in trauma patients requiring
      interfacility transfer to higher levels of care. DESIGN, SETTING AND
      PARTICIPANTS: Retrospective study of consecutively transferred trauma patients
      into a level-II trauma centre from 2013 to 2014. INTERVENTIONS: None. OUTCOME
      MEASURES: Mortality, intensive care unit (ICU) admission, operative procedure,
      MEWS deterioration in-transit, air transport interfacility, secondary overtriage
      (low injury severity score (ISS) <10, LOS<1 day, discharged home) and severe
      injury (ISS >=16). The association between the pretransfer MEWS and outcomes were
      analysed with Cochran-Armitage trend tests, receiver operator characteristic
      (ROC) curves and univariate logistic regression. RESULTS: There were 587
      transferred patients; outcomes were reported in 339 patients with complete data
      on all five vital signs used to calculate the MEWS. The MEWS ranged from 0 to 9
      (median of 1). There was a significant linear relationship between MEWS and study
      outcomes, especially mortality, ICU admission, air medical transport and severe
      injury (p<0.001 for all). A threshold score >=4 was identified by ROC analysis;
      11.2% of patients had MEWS >=4. Outcomes were significantly worse in patients
      with MEWS >=4 versus <4: mortality (26.2% vs 3.0%, OR=11.59, p<0.001); ICU
      admission (73.7% vs 47.2%, OR=3.14, p=0.003); air transfer (42.1% vs 15.6%,
      OR=3.93, p<0.001) and severe injury (59.5% vs 27.2%, OR=3.9, p<0.001). The MEWS
      was not associated with surgery, in-transit MEWS deterioration or secondary
      overtriage. CONCLUSION: Pretransfer MEWS >=4 may be used by the receiving
      facility for predicting injury severity, mortality, air transport and ICU
      resource use. In the interfacility transport setting, the MEWS may be useful for
      identifying patients with less obvious need for transfer or requiring more
      expeditious transfer.

PMID- 28490567
TI  - Validity and reliability of the Patient Centred Assessment Method for patient
      complexity and relationship with hospital length of stay: a prospective cohort
      study.
AB  - OBJECTIVES: Several instruments for evaluating patient complexity have been
      developed from a biopsychosocial perspective. Although relationships between the
      results obtained by these instruments and the length of stay in hospital have
      been examined, many instruments are complicated and not easy to use. The Patient
      Centred Assessment Method (PCAM) is a candidate for practical use. This study
      aimed to test the validity and reliability of the PCAM and examine the
      correlations between length of hospital stay and PCAM scores in a regional
      secondary care hospital in Japan. DESIGN: Prospective cohort study. PARTICIPANTS
      AND SETTING: Two hundred and one patients admitted to Ouji Coop Hospital between
      July 2014 and September 2014. MAIN PREDICTOR: PCAM total score in initial phase
      of hospital admission. MAIN OUTCOME: Length of stay in hospital. RESULTS: Among
      201 patients (Female/Male=98/103) with mean (SD) age of 77.4+/-11.9 years, the
      mean PCAM score was 25+/-7.3 and mean (SD) length of stay in hospital (LOS)
      34.1+/-40.9 days. Using exploratory factor analysis to examine construct
      validity, PCAM evidently has a two-factor structure, comprising medicine-oriented
      and patient-oriented complexity. The Spearman rank correlation coefficient for
      evaluating criterion-based validity between PCAM and INTERMED was 0.90. For
      reliability, Cronbach's alpha was 0.85. According to negative binomial regression
      analyses, PCAM scores are a statistically significant predictor (p<0.001) of LOS
      after adjusting for age, gender, Mini Nutritional Assessment Short-Form, Charlson
      Comorbidity Index, serum sodium concentration, total number of medications and
      whether public assistance was required. In another model, each factor in PCAM was
      independently correlated with length of stay in hospital after adjustment
      (medicine-oriented complexity: p=0.001, patient-oriented complexity: p=0.014).
      CONCLUSION: PCAM is a reliable and valid measurement of patient complexity and
      PCAM scores have a significant correlation with hospital length of stay.

PMID- 28490568
TI  - Noninvasive detection of F8 int22h-related inversions and sequence variants in
      maternal plasma of hemophilia carriers.
AB  - Direct detection of F8 and F9 sequence variants in maternal plasma of hemophilia
      carriers has been demonstrated by microfluidics digital PCR. Noninvasive prenatal
      assessment of the most clinically relevant group of sequence variants among
      patients with hemophilia, namely, those involving int22h-related inversions
      disrupting the F8 gene, poses additional challenges because of its molecular
      complexity. We investigated the use of droplet digital PCR (ddPCR) and targeted
      massively parallel sequencing (MPS) for maternal plasma DNA analysis to
      noninvasively determine fetal mutational status in pregnancies at risk for
      hemophilia. We designed family-specific ddPCR assays to detect causative sequence
      variants scattered across the F8 and F9 genes. A haplotype-based approach coupled
      with targeted MPS was applied to deduce fetal genotype by capturing a 7.6-Mb
      region spanning the F8 gene in carriers with int22h-related inversions. The ddPCR
      analysis correctly determined fetal hemophilia status in 15 at-risk pregnancies
      in samples obtained from 8 to 42 weeks of gestation. There were 3 unclassified
      samples, but no misclassification. Detailed fetal haplotype maps of the F8 gene
      region involving int22h-related inversions obtained through targeted MPS enabled
      correct diagnoses of fetal mutational status in 3 hemophilia families. Our data
      suggest it is feasible to apply targeted MPS to interrogate maternally inherited
      F8 int22h-related inversions, whereas ddPCR represents an affordable approach for
      the identification of F8 and F9 sequence variants in maternal plasma. These
      advancements may bring benefits for the pregnancy management for carriers of
      hemophilia sequence variants; in particular, the common F8 int22h-related
      inversions, associated with the most severe clinical phenotype.

PMID- 28490569
TI  - Safety and tolerability of pembrolizumab in patients with relapsed/refractory
      primary mediastinal large B-cell lymphoma.
AB  - Treatment options for relapsed/refractory primary mediastinal large B-cell
      lymphoma (rrPMBCL) are limited, and prognosis is generally poor (overall response
      rate [ORR] 0% to 25%; 2-year overall survival 15%). PMBCL frequently involves PD
      1 ligand overexpression, potentially making PMBCL particularly susceptible to PD
      1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti
      PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort phase 1b trial.
      At time of data cutoff, 18 patients (median age 30 years; median 3 prior lines of
      therapy) had been enrolled and treated, of whom 17 were included in the efficacy
      analyses. Eleven patients (61%) experienced drug-related adverse events (mostly
      grade 1-2); none discontinued treatment due to adverse events. ORR was 41%
      (7/17); 6 additional patients (35%) had stable disease. Of patients evaluable by
      imaging, 13 out of 16 (81%) had decreases in target lesions. With a median follow
      up of 11.3 months, median duration of response was not reached. Two patients
      reached the maximum 2-year treatment duration and remain in remission. Median
      overall survival was not reached for treated patients overall; all responders
      were still alive at data cutoff. These results in heavily pretreated rrPMBCL
      patients demonstrate that PD-1 blockade with pembrolizumab has a manageable
      safety profile and promising antitumor activity. This trial was registered at
      www.clinicaltrials.gov as #NCT01953692.

PMID- 28490571
TI  - Evaluating a CLL susceptibility variant in ITGB2 in families with multiple
      subtypes of hematological malignancies.

PMID- 28490570
TI  - Mouse RUNX1C regulates premegakaryocytic/erythroid output and maintains survival
      of megakaryocyte progenitors.
AB  - RUNX1 is crucial for the regulation of megakaryocyte specification, maturation,
      and thrombopoiesis. Runx1 possesses 2 promoters: the distal P1 and proximal P2
      promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and
      RUNX1B, respectively, which differ solely in their N-terminal amino acid
      sequences. RUNX1C is the most abundantly expressed isoform in adult
      hematopoiesis, present in all RUNX1-expressing populations, including the cKit+
      hematopoietic stem and progenitor cells. RUNX1B expression is more restricted,
      being highly expressed in the megakaryocyte lineage but downregulated during
      erythropoiesis. We generated a Runx1 P1 knock-in of RUNX1B, termed P1-MRIPV This
      mouse line lacks RUNX1C expression but has normal total RUNX1 levels, solely
      comprising RUNX1B. Using this mouse line, we establish a specific requirement for
      the P1-RUNX1C isoform in megakaryopoiesis, which cannot be entirely compensated
      for by RUNX1B overexpression. P1 knock-in megakaryocyte progenitors have reduced
      proliferative capacity and undergo increased cell death, resulting in
      thrombocytopenia. P1 knock-in premegakaryocyte/erythroid progenitors demonstrate
      an erythroid-specification bias, evident from increased erythroid colony-forming
      ability and decreased megakaryocyte output. At a transcriptional level, multiple
      erythroid-specific genes are upregulated and megakaryocyte-specific transcripts
      are downregulated. In addition, proapoptotic pathways are activated in P1 knock
      in premegakaryocyte/erythroid progenitors, presumably accounting for the
      increased cell death in the megakaryocyte progenitor compartment. Unlike in the
      conditional adult Runx1 null models, megakaryocytic maturation is not affected in
      the P1 knock-in mice, suggesting that RUNX1B can regulate endomitosis and
      thrombopoiesis. Therefore, despite the high degree of structural similarity,
      RUNX1B and RUNX1C isoforms have distinct and specific roles in adult
      megakaryopoiesis.

PMID- 28490572
TI  - Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by
      single-cell analysis.
AB  - Genomic studies have revealed significant branching heterogeneity in cancer.
      Studies of resistance to tyrosine kinase inhibitor therapy have not fully
      reflected this heterogeneity because resistance in individual patients has been
      ascribed to largely mutually exclusive on-target or off-target mechanisms in
      which tumors either retain dependency on the target oncogene or subvert it
      through a parallel pathway. Using targeted sequencing from single cells and
      colonies from patient samples, we demonstrate tremendous clonal diversity in the
      majority of acute myeloid leukemia (AML) patients with activating FLT3 internal
      tandem duplication mutations at the time of acquired resistance to the FLT3
      inhibitor quizartinib. These findings establish that clinical resistance to
      quizartinib is highly complex and reflects the underlying clonal heterogeneity of
      AML.

PMID- 28490573
TI  - DOK7 gene therapy enhances motor activity and life span in ALS model mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor
      neurodegenerative disease with severe muscle atrophy. The glutamate release
      inhibitor riluzole is the only medication approved by the FDA, and prolongs
      patient life span by a few months, testifying to a strong need for new treatment
      strategies. In ALS, motor neuron degeneration first becomes evident at the motor
      nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse
      between motor neuron and skeletal muscle; degeneration then progresses
      proximally, implicating the NMJ as a therapeutic target. We previously
      demonstrated that activation of muscle-specific kinase MuSK by the cytoplasmic
      protein Dok-7 is essential for NMJ formation, and forced expression of Dok-7 in
      muscle activates MuSK and enlarges NMJs. Here, we show that therapeutic
      administration of an adeno-associated virus vector encoding the human DOK7 gene
      suppressed motor nerve terminal degeneration at NMJs together with muscle atrophy
      in the SOD1-G93A ALS mouse model. Ultimately, we show that DOK7 gene therapy
      enhanced motor activity and life span in ALS model mice.

PMID- 28490574
TI  - Early Emergence of CD19-Negative Human Antibody-Secreting Cells at the
      Plasmablast to Plasma Cell Transition.
AB  - Long-lived human plasma cells (PCs) play central roles in immunity and
      autoimmunity and are enriched among the subpopulation of CD19neg human PCs.
      However, whether human CD19neg PCs are necessarily aged cells that have gradually
      lost CD19 expression is not known. Assessing peripheral blood samples at steady
      state and during the acute response to influenza vaccination in healthy donors,
      we identify the presence of phenotypic CD19neg plasmablasts, the proliferative
      precursor state to mature PCs, and demonstrate by ELISPOT that these are Ab
      secreting cells (ASCs). During the acute response to influenza vaccination,
      CD19pos, CD19low, and CD19neg ASCs secrete vaccine-specific Abs and show linked
      IGHV repertoires. To address precursor/product relationships, we use in vitro
      models that mimic T-dependent and T-independent differentiation, finding that the
      CD19neg state can be established at the plasmablast to PC transition, that
      CD19neg PCs increase as a percentage of surviving PCs in vitro, and that CD19neg
      and CD19pos PCs can be maintained independently. These data provide proof-of
      principle for the view that newly generated ASCs can acquire a mature PC
      phenotype that is accompanied by loss of CD19 expression at an early stage of
      differentiation and that aging is not an obligate requirement for a CD19neg state
      to be established.

PMID- 28490575
TI  - EZH2 Regulates the Developmental Timing of Effectors of the Pre-Antigen Receptor
      Checkpoints.
AB  - The histone methyltransferase EZH2 is required for B and T cell development;
      however, the molecular mechanisms underlying this requirement remain elusive. In
      a murine model of lymphoid-specific EZH2 deficiency we found that EZH2 was
      required for proper development of adaptive, but not innate, lymphoid cells. In
      adaptive lymphoid cells EZH2 prevented the premature expression of Cdkn2a and the
      consequent stabilization of p53, an effector of the pre-Ag receptor checkpoints.
      Deletion of Cdkn2a in EZH2-deficient lymphocytes prevented p53 stabilization,
      extended lymphocyte survival, and restored differentiation resulting in the
      generation of mature B and T lymphocytes. Our results uncover a crucial role for
      EZH2 in adaptive lymphocytes to control the developmental timing of effectors of
      the pre-Ag receptor checkpoints.

PMID- 28490576
TI  - Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils
      Exerting Fundamental Immunometabolic Effects.
AB  - During sepsis, excessive activation of the complement system with generation of
      the anaphylatoxin C5a results in profound disturbances in crucial neutrophil
      functions. Moreover, because neutrophil activity is highly dependent on
      intracellular pH (pHi), we propose a direct mechanistic link between complement
      activation and neutrophil pHi In this article, we demonstrate that in vitro
      exposure of human neutrophils to C5a significantly increased pHi by selective
      activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated
      intracellular alkalinization was dependent on C5aR1, intracellular calcium,
      protein kinase C, and calmodulin, and downstream signaling regulated the release
      of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by
      C5a increased the glucose uptake and activated glycolytic flux in neutrophils,
      resulting in a significant release of lactate. Furthermore, C5a induced
      acidification of the extracellular micromilieu. In experimental murine sepsis,
      pHi of blood neutrophils was analogously alkalinized, which could be normalized
      by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients
      with septic shock likewise exhibited a significantly increased pHi These data
      suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate
      pHi balance in neutrophils resulting in profound inflammatory and metabolic
      changes that contribute to hyperlactatemia during sepsis.

PMID- 28490577
TI  - Five minutes with . . . Kate Lovett.

PMID- 28490580
TI  - What is the overlap between HIV and shigellosis epidemics in England: further
      evidence of MSM transmission?
AB  - BACKGROUND: Evidence suggests that sexual transmission between men has replaced
      foreign travel as the predominant mode of Shigella transmission in England.
      However, sexuality and HIV status are not routinely recorded for laboratory
      reported Shigella, and the role of HIV in the Shigella epidemic is not well
      understood. METHODS: The Modular Open Laboratory Information System containing
      all Shigella cases reported to Public Health England (PHE) and the PHE HIV and
      AIDS Reporting System holding all adults living with diagnosed HIV in England
      were matched using a combination of Soundex code, date of birth and gender.
      RESULTS: From 2004 to 2015, 88 664 patients were living with HIV, and 10 269
      Shigella cases were reported in England; 9% (873/10 269) of Shigella cases were
      diagnosed with HIV, of which 93% (815/873) were in men. Shigella cases without
      reported travel history were more likely to be living with HIV than those who had
      travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the
      incidence of Shigella in men with HIV rose from 47/100 000 to 226/100 000
      (p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the
      study period (0-24/100 000). Among Shigella cases without travel and with HIV,
      91% (657/720) were men who have sex with men (MSM). HIV preceded Shigella
      diagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50
      copies/mL). DISCUSSION: We observed a sustained increase in the national rate of
      shigellosis in MSM with HIV, who may experience more serious clinical disease.
      Sexual history, HIV status and STI risk might require sensitive investigation in
      men presenting with gastroenteritis.

PMID- 28490582
TI  - Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity.
AB  - Human cytomegalovirus (HCMV) is the most common viral infection acquired by the
      developing human fetus and can result in damage to the developing central nervous
      system. Although vaccine development to modify this congenital infection is
      ongoing, the unique epidemiology of maternal HCMV infections appears discordant
      with strategies for vaccine development. Several characteristics of congenital
      HCMV infections suggest that the efficacy of vaccines designed to induce
      responses similar to those that follow natural infection will be limited.

PMID- 28490581
TI  - Patterns of prevalent HPV and STI co-infections and associated factors among HIV
      negative young Western Cape, South African women: the EVRI trial.
AB  - OBJECTIVE: To estimate the prevalence and describe the patterns of concurrent
      human papillomavirus (HPV) and STIs and associated factors among HIV-negative
      young Western Cape, South African women participating in the Efficacy of HPV
      Vaccine to Reduce HIV Infection (EVRI) trial. METHODS: HIV-negative women aged 16
      24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to
      receive the licensed four-valent HPV vaccine or placebo. At study entry,
      participants were clinically evaluated for five STIs: herpes simplex virus type 2
      (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes
      (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history
      characteristics were compared among women with STI co-infections, single
      infection and no infection using Pearson chi2 and Mann-Whitney tests. ORs were
      calculated to evaluate factors associated with STI co-infection prevalence.
      RESULTS: Among 388 young women, STI co-infection prevalence was high: 47% had >=2
      concurrent STIs, 36% had a single STI and 17% had none of the five evaluated
      STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by
      HPV/HSV-2/Chlamydia trachomatis (CT) (17%) and HPV/CT (15%). Co-infection
      prevalence was independently associated with alcohol use (adjusted OR=2.01, 95%
      CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95%
      CI 1.53 to 30.08). CONCLUSIONS: Among high-risk young women from underserved
      communities such as in Southern Africa, a multicomponent prevention strategy that
      integrates medical and behavioural interventions targeting both men and women is
      essential to prevent acquisition of concurrent STI infections and consequent
      disease. TRIAL REGISTRATION NUMBER: NCT01489527; Post-results.

PMID- 28490578
TI  - Investigating Clinical Issues by Genotyping of Medically Important Fungi: Why and
      How?
AB  - Genotyping studies of medically important fungi have addressed elucidation of
      outbreaks, nosocomial transmissions, infection routes, and genotype-phenotype
      correlations, of which secondary resistance has been most intensively
      investigated. Two methods have emerged because of their high discriminatory power
      and reproducibility: multilocus sequence typing (MLST) and microsatellite length
      polymorphism (MLP) using short tandem repeat (STR) markers. MLST relies on single
      nucleotide polymorphisms within the coding regions of housekeeping genes. STR
      polymorphisms are based on the number of repeats of short DNA fragments, mostly
      outside coding regions, and thus are expected to be more polymorphic and more
      rapidly evolving than MLST markers. There is no consensus on a universal typing
      system. Either one or both of these approaches are now available for Candida
      spp., Aspergillus spp., Fusarium spp., Scedosporium spp., Cryptococcus
      neoformans, Pneumocystis jirovecii, and endemic mycoses. The choice of the method
      and the number of loci to be tested depend on the clinical question being
      addressed. Next-generation sequencing is becoming the most appropriate method for
      fungi with no MLP or MLST typing available. Whatever the molecular tool used,
      collection of clinical data (e.g., time of hospitalization and sharing of similar
      rooms) is mandatory for investigating outbreaks and nosocomial transmission.

PMID- 28490583
TI  - Structural Definition of Duck Major Histocompatibility Complex Class I Molecules
      That Might Explain Efficient Cytotoxic T Lymphocyte Immunity to Influenza A
      Virus.
AB  - A single dominantly expressed allele of major histocompatibility complex class I
      (MHC I) may be responsible for the duck's high tolerance to highly pathogenic
      influenza A virus (HP-IAV) compared to the chicken's lower tolerance. In this
      study, the crystal structures of duck MHC I (Anpl-UAA*01) and duck beta2
      microglobulin (beta2m) with two peptides from the H5N1 strains were determined.
      Two remarkable features were found to distinguish the Anpl-UAA*01 complex from
      other known MHC I structures. A disulfide bond formed by Cys95 and Cys112 and
      connecting the beta5 and beta6 sheets at the bottom of peptide binding groove
      (PBG) in Anpl-UAA*01 complex, which can enhance IAV peptide binding, was
      identified. Moreover, the interface area between duck MHC I and beta2m was found
      to be larger than in other species. In addition, the two IAV peptides that
      display distinctive conformations in the PBG, B, and F pockets act as the primary
      anchor sites. Thirty-one IAV peptides were used to verify the peptide binding
      motif of Anpl-UAA*01, and the results confirmed that the peptide binding motif is
      similar to that of HLA-A*0201. Based on this motif, approximately 600 peptides
      from the IAV strains were partially verified as the candidate epitope peptides
      for Anpl-UAA*01, which is a far greater number than those for chicken BF2*2101
      and BF2*0401 molecules. Extensive IAV peptide binding should allow for ducks with
      this Anpl-UAA*01 haplotype to resist IAV infection.IMPORTANCE Ducks are natural
      reservoirs of influenza A virus (IAV) and are more resistant to the IAV than
      chickens. Both ducks and chickens express only one dominant MHC I locus providing
      resistance to the virus. To investigate how MHC I provides IAV resistance,
      crystal structures of the dominantly expressed duck MHC class I (pAnpl-UAA*01)
      with two IAV peptides were determined. A disulfide bond was identified in the
      peptide binding groove that can facilitate Anpl-UAA*01 binding to IAV peptides.
      Anpl-UAA*01 has a much wider recognition spectrum of IAV epitope peptides than do
      chickens. The IAV peptides bound by Anpl-UAA*01 display distinctive conformations
      that can help induce an extensive cytotoxic T lymphocyte (CTL) response. In
      addition, the interface area between the duck MHC I and beta2m is larger than in
      other species. These results indicate that HP-IAV resistance in ducks is due to
      extensive CTL responses induced by MHC I.

PMID- 28490584
TI  - A Naturally Occurring Recombinant Enterovirus Expresses a Torovirus
      Deubiquitinase.
AB  - Enteroviruses (EVs) are implicated in a wide range of diseases in humans and
      animals. In this study, a novel enterovirus (enterovirus species G [EVG]) (EVG
      08/NC_USA/2015) was isolated from a diagnostic sample from a neonatal pig
      diarrhea case and identified by using metagenomics and complete genome
      sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic
      EVG strain (PEV9 UKG/410/73). Remarkably, a 582-nucleotide insertion, flanked by
      3Cpro cleavage sites at the 5' and 3' ends, was found in the 2C/3A junction
      region of the viral genome. This insertion encodes a predicted protease with 54
      to 68% amino acid identity to torovirus (ToV) papain-like protease (PLP) (ToV
      PLP). Structural homology modeling predicts that this protease adopts a fold and
      a catalytic site characteristic of minimal PLP catalytic domains. This structure
      is similar to those of core catalytic domains of the foot-and-mouth disease virus
      leader protease and coronavirus PLPs, which act as deubiquitinating and
      deISGylating (interferon [IFN]-stimulated gene 15 [ISG15]-removing) enzymes on
      host cell substrates. Importantly, the recombinant ToV-PLP protein derived from
      this novel enterovirus also showed strong deubiquitination and deISGylation
      activities and demonstrated the ability to suppress IFN-beta expression. Using
      reverse genetics, we generated a ToV-PLP knockout recombinant virus. Compared to
      the wild-type virus, the ToV-PLP knockout mutant virus showed impaired growth and
      induced higher expression levels of innate immune genes in infected cells. These
      results suggest that ToV-PLP functions as an innate immune antagonist;
      enterovirus G may therefore gain fitness through the acquisition of ToV-PLP from
      a recombination event.IMPORTANCE Enteroviruses comprise a highly diversified
      group of viruses. Genetic recombination has been considered a driving force for
      viral evolution; however, recombination between viruses from two different orders
      is a rare event. In this study, we identified a special case of cross-order
      recombination between enterovirus G (order Picornavirales) and torovirus (order
      Nidovirales). This naturally occurring recombination event may have broad
      implications for other picornaviral and/or nidoviral species. Importantly, we
      demonstrated that the exogenous ToV-PLP gene that was inserted into the EVG
      genome encodes a deubiquitinase/deISGylase and potentially suppresses host
      cellular innate immune responses. Our results provide insights into how a gain of
      function through genetic recombination, in particular cross-order recombination,
      may improve the ability of a virus to evade host immunity.

PMID- 28490585
TI  - Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics
      and Specificities of Antibody Responses against HIV-1 Env in Macaques.
AB  - Evaluation of the epitope specificities, locations (systemic or mucosal), and
      effector functions of antibodies elicited by novel HIV-1 immunogens engineered to
      improve exposure of specific epitopes is critical for HIV-1 vaccine development.
      Utilizing an array of humoral assays, we evaluated the magnitudes, epitope
      specificities, avidities, and functions of systemic and mucosal immune responses
      elicited by a vaccine regimen containing Env cross-linked to a CD4-mimetic
      miniprotein (gp140-M64U1) in rhesus macaques. Cross-linking of gp140 Env to M64U1
      resulted in earlier increases of both the magnitude and avidity of the IgG
      binding response than those with Env protein alone. Notably, IgG binding
      responses at an early time point correlated with antibody-dependent cellular
      cytotoxicity (ADCC) function at the peak immunity time point, which was higher
      for the cross-linked Env group than for the Env group. In addition, the cross
      linked Env group developed higher IgG responses against a linear epitope in the
      gp120 C1 region of the HIV-1 envelope glycoprotein. These data demonstrate that
      structural modification of the HIV-1 envelope immunogen by cross-linking of gp140
      with the CD4-mimetic M64U1 elicited an earlier increase of binding antibody
      responses and altered the specificity of the IgG responses, correlating with the
      rise of subsequent antibody-mediated antiviral functions.IMPORTANCE The
      development of an efficacious HIV-1 vaccine remains a global priority to prevent
      new cases of HIV-1 infection. Of the six HIV-1 efficacy trials to date, only one
      has demonstrated partial efficacy, and immune correlate analysis of that trial
      revealed a role for binding antibodies and antibody Fc-mediated effector
      functions. New HIV-1 envelope immunogens are being engineered to selectively
      expose the most vulnerable and conserved sites on the HIV-1 envelope, with the
      goal of eliciting antiviral antibodies. Evaluation of the humoral responses
      elicited by these novel immunogen designs in nonhuman primates is critical for
      understanding how to improve upon immunogen design to inform further testing in
      human clinical trials. Our results demonstrate that structural modifications of
      Env that aim to mimic the CD4-bound conformation can result in earlier antibody
      elicitation, altered epitope specificity, and increased antiviral function
      postimmunization.

PMID- 28490586
TI  - Deletion of the K1L Gene Results in a Vaccinia Virus That Is Less Pathogenic Due
      to Muted Innate Immune Responses, yet Still Elicits Protective Immunity.
AB  - All viruses strategically alter the antiviral immune response to their benefit.
      The vaccinia virus (VACV) K1 protein has multiple immunomodulatory effects in
      tissue culture models of infection, including NF-kappaB antagonism. However, the
      effect of K1 during animal infection is poorly understood. We determined that a
      K1L-less vaccinia virus (vDeltaK1L) was less pathogenic than wild-type VACV in
      intranasal and intradermal models of infection. Decreased pathogenicity was
      correlated with diminished virus replication in intranasally infected mice.
      However, in intradermally inoculated ears, vDeltaK1L replicated to levels nearly
      identical to those of VACV, implying that the decreased immune response to
      vDeltaK1L infection, not virus replication, dictated lesion size. Several lines
      of evidence support this theory. First, vDeltaK1L induced slightly less edema
      than vK1L, as revealed by histopathology and noninvasive quantitative ultrasound
      technology (QUS). Second, infiltrating immune cell populations were decreased in
      vDeltaK1L-infected ears. Third, cytokine and chemokine gene expression was
      decreased in vDeltaK1L-infected ears. While these results identified the
      biological basis for smaller lesions, they remained puzzling; because K1
      antagonizes NF-kappaB in vitro, antiviral gene expression was expected to be
      higher during vDeltaK1L infection. Despite these diminished innate immune
      responses, vDeltaK1L vaccination induced a protective VACV-specific CD8+ T cell
      response and protected against a lethal VACV challenge. Thus, vDeltaK1L is the
      first vaccinia virus construct reported that caused a muted innate immune gene
      expression profile and decreased immune cell infiltration in an intradermal model
      of infection yet still elicited protective immunity.IMPORTANCE The vaccinia virus
      (VACV) K1 protein inhibits NF-kappaB activation among its other antagonistic
      functions. A virus lacking K1 (vDeltaK1L) was predicted to be less pathogenic
      because it would trigger a more robust antiviral immune response than VACV.
      Indeed, vDeltaK1L was less pathogenic in intradermally infected mouse ear pinnae.
      However, vDeltaK1L infection unexpectedly elicited dramatically reduced
      infiltration of innate immune cells into ears. This was likely due to decreased
      expression of cytokine and chemokine genes in vDeltaK1L-infected ears. As such,
      our finding contradicted observations from cell culture systems. Interestingly,
      vDeltaK1L conferred protective immunity against lethal VACV challenge. This
      suggests that the muted immune response triggered during vDeltaK1L infection
      remained sufficient to mount an effective protective response. Our results
      highlight the complexity and unpredictable nature of virus-host interactions, a
      relationship that must be understood to better comprehend virus pathogenesis or
      to manipulate viruses for use as vaccines.

PMID- 28490579
TI  - Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.
AB  - Since the reclassification of the genus Bartonella in 1993, the number of species
      has grown from 1 to 45 currently designated members. Likewise, the association of
      different Bartonella species with human disease continues to grow, as does the
      range of clinical presentations associated with these bacteria. Among these,
      blood-culture-negative endocarditis stands out as a common, often undiagnosed,
      clinical presentation of infection with several different Bartonella species. The
      limitations of laboratory tests resulting in this underdiagnosis of Bartonella
      endocarditis are discussed. The varied clinical picture of Bartonella infection
      and a review of clinical aspects of endocarditis caused by Bartonella are
      presented. We also summarize the current knowledge of the molecular basis of
      Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella
      species that most commonly cause endocarditis, B. henselae and B. quintana. We
      discuss evidence that surface adhesins are important factors for autoaggregation
      and biofilm formation by Bartonella species. Finally, we propose that biofilm
      formation is a critical step in the formation of vegetative masses during
      Bartonella-mediated endocarditis and represents a potential reservoir for
      persistence by these bacteria.

PMID- 28490587
TI  - Heparanase Upregulation Contributes to Porcine Reproductive and Respiratory
      Syndrome Virus Release.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause
      substantial economic losses to the pig industry worldwide. Heparan sulfate (HS)
      is used by PRRSV for initial attachment to target cells. However, the role of HS
      in the late phase of PRRSV infection and the mechanism of virus release from host
      cells remain largely unknown. In this study, we showed that PRRSV infection
      caused a decrease in HS expression and upregulated heparanase, the only known
      enzyme capable of degrading HS. We subsequently demonstrated that the NF-kappaB
      signaling pathway and cathepsin L protease were involved in regulation of PRRSV
      infection-induced heparanase. In addition, we found that ablation of heparanase
      expression using small interfering RNA duplexes increased cell surface expression
      of HS and suppressed PRRSV replication and release, whereas overexpression of
      heparanase reduced HS surface expression and enhanced PRRSV replication and
      release. These data suggest that PRRSV activates NF-kappaB and cathepsin L to
      upregulate and process heparanase, and then the active heparanase cleaves HS,
      resulting in viral release. Our findings provide new insight into the molecular
      mechanism of PRRSV egress from host cells, which might help us to further
      understand PRRSV pathogenesis.IMPORTANCE Porcine reproductive and respiratory
      syndrome virus (PRRSV) causes great economic losses each year to the pig industry
      worldwide. The molecular mechanism of PRRSV release from host cells largely
      remains a mystery. In this study, we demonstrate that PRRSV activates NF-kappaB
      and cathepsin L to upregulate and process heparanase, and then the active
      heparanase is released to the extracellular space and exerts enzymatic activity
      to cleave heparan sulfate, resulting in viral release. Our findings provide new
      insight into the molecular mechanism of PRRSV egress from host cells, which might
      help us to further understand PRRSV pathogenesis.

PMID- 28490588
TI  - Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That
      Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States.
AB  - The envelope glycoproteins (Envs) on the surfaces of HIV-1 particles are targeted
      by host antibodies. Primary HIV-1 isolates demonstrate different global
      sensitivities to antibody neutralization; tier-1 isolates are sensitive, whereas
      tier-2 isolates are more resistant. Single-site mutations in Env can convert tier
      2 into tier-1-like viruses. We hypothesized that such global change in
      neutralization sensitivity results from weakening of intramolecular interactions
      that maintain Env integrity. Three strategies commonly applied to perturb protein
      structure were tested for their effects on global neutralization sensitivity:
      exposure to low temperature, Env-activating ligands, and a chaotropic agent. A
      large panel of diverse tier-2 isolates from clades B and C was analyzed.
      Incubation at 0 degrees C, which globally weakens hydrophobic interactions,
      causes gradual and reversible exposure of the coreceptor-binding site. In the
      cold-induced state, Envs progress at isolate-specific rates to unstable forms
      that are sensitive to antibody neutralization and then gradually lose function.
      Agents that mimic the effects of CD4 (CD4Ms) also induce reversible structural
      changes to states that exhibit isolate-specific stabilities. The chaotropic agent
      urea (at low concentrations) does not affect the structure or function of native
      Env. However, urea efficiently perturbs metastable states induced by cold and
      CD4Ms and increases their sensitivity to antibody neutralization and their
      inactivation rates Therefore, chemical and physical agents can guide Env from the
      stable native state to perturbation-sensitive forms and modulate their stability
      to bestow tier-1-like properties on primary tier-2 strains. These concepts can be
      applied to enhance the potency of vaccine-elicited antibodies and microbicides at
      mucosal sites of HIV-1 transmission.IMPORTANCE An effective vaccine to prevent
      transmission of HIV-1 is a primary goal of the scientific and health care
      communities. Vaccine-elicited antibodies target the viral envelope glycoproteins
      (Envs) and can potentially inhibit infection. However, the potency of such
      antibodies is generally low. Single-site mutations in Env can enhance the global
      sensitivity of HIV-1 to neutralization by antibodies. We found that such a
      hypersensitivity phenotype can also be induced by agents that destabilize protein
      structure. Exposure to 0 degrees C or low concentrations of Env-activating
      ligands gradually guides Env to metastable forms that expose cryptic epitopes and
      that are highly sensitive to neutralization. Low concentrations of the chaotropic
      agent urea do not affect native Env but destabilize perturbed states induced by
      cold or CD4Ms and increase their neutralization. The concept of enhancing
      antibody sensitivity by chemical agents that affect the structural stability of
      proteins can be applied to increase the potency of topical microbicides and
      vaccine-elicited antibodies.

PMID- 28490589
TI  - Roles of M1 and M2 Macrophages in Herpes Simplex Virus 1 Infectivity.
AB  - Macrophages are the predominant infiltrate in the corneas of mice that have been
      ocularly infected with herpes simplex virus 1 (HSV-1). However, very little is
      known about the relative roles of M1 (classically activated or polarized) and M2
      (alternatively activated or polarized) macrophages in ocular HSV-1 infection. To
      better understand these relationships, we assessed the impact of directed M1 or
      M2 activation of RAW264.7 macrophages and peritoneal macrophages (PM) on
      subsequent HSV-1 infection. In both the RAW264.7 macrophage and PM in vitro
      models, HSV-1 replication in M1 macrophages was markedly lower than in M2
      macrophages and unstimulated controls. The M1 macrophages expressed significantly
      higher levels of 28 of the 32 tested cytokines and chemokines than M2
      macrophages, with HSV-1 infection significantly increasing the levels of
      proinflammatory cytokines and chemokines in the M1 versus the M2 macrophages. To
      examine the effects of shifting the immune response toward either M1 or M2
      macrophages in vivo, wild-type mice were injected with gamma interferon (IFN
      gamma) DNA or colony-stimulating factor 1 (CSF-1) DNA prior to ocular infection
      with HSV-1. Virus replication in the eye, latency in trigeminal ganglia (TG), and
      markers of T cell exhaustion in the TG were determined. We found that injection
      of mice with IFN-gamma DNA, which enhances the development of M1 macrophages,
      increased virus replication in the eye; increased latency; and also increased
      CD4, CD8, IFN-gamma, and PD-1 transcripts in the TG of latently infected mice.
      Conversely, injection of mice with CSF-1 DNA, which enhances the development of
      M2 macrophages, was associated with reduced virus replication in the eye and
      reduced latency and reduced the levels of CD4, CD8, IFN-gamma,and PD-1
      transcripts in the TG. Collectively, these results suggest that M2 macrophages
      directly reduce the levels of HSV-1 latency and, thus, T-cell exhaustion in the
      TG of ocularly infected mice.IMPORTANCE Our findings demonstrate a novel approach
      to further reducing HSV-1 replication in the eye and latency in the TG by
      modulating immune components, specifically, by altering the phenotype of
      macrophages. We suggest that inclusion of CSF-1 as part of any vaccination
      regimen against HSV infection to coax responses of macrophages toward an M2,
      rather than an M1, response may further improve vaccine efficacy against ocular
      HSV-1 replication and latency.

PMID- 28490590
TI  - The C Terminus of the Herpes Simplex Virus UL25 Protein Is Required for Release
      of Viral Genomes from Capsids Bound to Nuclear Pores.
AB  - The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion
      of viral and host membranes, whereupon dynein-dependent trafficking along
      microtubules targets it to the nuclear envelope. Binding of the capsid to the
      nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid
      tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and
      pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been
      difficult to study due to the rapid release of the genome once the capsid
      interacts with the nuclear pore. In this study, we describe the isolation and
      characterization of a truncation mutant of pUL25. Live-cell imaging and
      immunofluorescence studies demonstrated that the mutant was not impaired in
      penetration of the host cell or in trafficking of the capsid to the nuclear
      membrane. However, expression of viral proteins was absent or significantly
      delayed in cells infected with the pUL25 mutant virus. Transmission electron
      microscopy revealed capsids accumulated at nuclear pores that retained the viral
      genome for at least 4 h postinfection. In addition, cryoelectron microscopy (cryo
      EM) reconstructions of virion capsids did not detect any obvious differences in
      the location or structural organization for the pUL25 or pUL36 proteins on the
      pUL25 mutant capsids. Further, in contrast to wild-type virus, the antiviral
      response mediated by the viral DNA-sensing cyclic guanine adenine synthase (cGAS)
      was severely compromised for the pUL25 mutant. These results demonstrate that the
      pUL25 capsid protein has a critical role in releasing viral DNA from NPC-bound
      capsids.IMPORTANCE Herpes simplex virus 1 (HSV-1) is the causative agent of
      several pathologies ranging in severity from the common cold sore to life
      threatening encephalitic infection. Early steps in infection include release of
      the capsid into the cytoplasm, docking of the capsid at a nuclear pore, and
      release of the viral genome into the nucleus. A key knowledge gap is how the
      capsid engages the NPC and what triggers release of the viral genome into the
      nucleus. Here we show that the C-terminal region of the HSV-1 pUL25 protein is
      required for releasing the viral genome from capsids docked at nuclear pores. The
      significance of our research is in identifying pUL25 as a key viral factor for
      genome uncoating. pUL25 is found at each of the capsid vertices as part of the
      capsid vertex-specific component and implicates the importance of this complex
      for NPC binding and genome release.

PMID- 28490591
TI  - Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein
      Attenuates Porcine Epidemic Diarrhea Virus in Piglets.
AB  - We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by
      blind serial passaging of the intestinal contents of a diarrheic piglet in Vero
      cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the
      tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion
      in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal,
      conventional suckling piglets with TC-PC177 or PC21A to compare their
      pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and
      lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe
      clinical signs and 55% mortality. To investigate whether infection with TC-PC177
      can induce cross-protection against challenge with a highly virulent PEDV strain,
      all the surviving piglets were challenged with PC21A at 3 weeks postinoculation.
      Compared with 100% protection in piglets initially inoculated with PC21A, 88% and
      100% TC-PC177- and mock-inoculated piglets had diarrhea following challenge,
      respectively, indicating incomplete cross-protection. To investigate whether this
      197-aa deletion was the determinant for the attenuation of TC-PC177, we generated
      a mutant (icPC22A-S1Delta197) bearing the 197-aa deletion from an infectious cDNA
      clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A).
      In neonatal gnotobiotic pigs, the icPC22A-S1Delta197 virus caused mild to
      moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the
      icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that
      deletion of this 197-aa fragment in the spike protein can attenuate a highly
      virulent PEDV, but the virus may lose important epitopes for inducing robust
      protective immunity.IMPORTANCE The emerging, highly virulent PEDV strains have
      caused substantial economic losses worldwide. However, the virulence determinants
      are not established. In this study, we found that a 197-aa deletion in the N
      terminal region of the S protein did not alter virus (TC-PC177) tissue tropism
      but reduced the virulence of the highly virulent PEDV strain PC22A in neonatal
      piglets. We also demonstrated that the primary infection with TC-PC177 failed to
      induce complete cross-protection against challenge by the highly virulent PEDV
      PC21A, suggesting that the 197-aa region may contain important epitopes for
      inducing protective immunity. Our results provide an insight into the role of
      this large deletion in virus propagation and pathogenicity. In addition, the
      reverse genetics platform of the PC22A strain was further optimized for the
      rescue of recombinant PEDV viruses in vitro This breakthrough allows us to
      investigate other virulence determinants of PEDV strains and will provide
      knowledge leading to better control PEDV infections.

PMID- 28490592
TI  - Epstein-Barr Virus Rta-Mediated Accumulation of DNA Methylation Interferes with
      CTCF Binding in both Host and Viral Genomes.
AB  - Rta, an Epstein-Barr virus (EBV) immediate-early protein, reactivates viral lytic
      replication that is closely associated with tumorigenesis. In previous studies,
      we demonstrated that in epithelial cells Rta efficiently induced cellular
      senescence, which is an irreversible G1 arrest likely to provide a favorable
      environment for productive replications of EBV and Kaposi's sarcoma-associated
      herpesvirus (KSHV). To restrict progression of the cell cycle, Rta simultaneously
      upregulates CDK inhibitors and downregulates MYC, CCND1, and JUN, among others.
      Rta has long been known as a potent transcriptional activator, thus its role in
      gene repression is unexpected. In silico analysis revealed that the promoter
      regions of MYC, CCND1, and JUN are common in (i) the presence of CpG islands,
      (ii) strong chromatin immunoprecipitation (ChIP) signals of CCCTC-binding factor
      (CTCF), and (iii) having at least one Rta binding site. By combining ChIP assays
      and DNA methylation analysis, here we provide evidence showing that Rta binding
      accumulated CpG methylation and decreased CTCF occupancy in the regulatory
      regions of MYC, CCND1, and JUN, which were associated with downregulated gene
      expression. Stable residence of CTCF in the viral latency and reactivation
      control regions is a hallmark of viral latency. Here, we observed that Rta
      mediated decreased binding of CTCF in the viral genome is concurrent with virus
      reactivation. Via interfering with CTCF binding, in the host genome Rta can
      function as a transcriptional repressor for gene silencing, while in the viral
      genome Rta acts as an activator for lytic gene loci by removing a topological
      constraint established by CTCF.IMPORTANCE CTCF is a multifunctional protein that
      variously participates in gene expression and higher-order chromatin structure of
      the cellular and viral genomes. In certain loci of the genome, CTCF occupancy and
      DNA methylation are mutually exclusive. Here, we demonstrate that the Epstein
      Barr virus (EBV) immediate-early protein, Rta, known to be a transcriptional
      activator, can also function as a transcriptional repressor. Via enriching CpG
      methylation and decreasing CTCF reloading, Rta binding efficiently shut down the
      expression of MYC, CCND1, and JUN, thus impeding cell cycle progression. Rta
      mediated disruption of CTCF binding was also detected in the latency/reactivation
      control regions of the EBV genome, and this in turn led to viral lytic cycle
      progression. As emerging evidence indicates that a methylated EBV genome is a
      preferable substrate for EBV Zta, the other immediate-early protein, our results
      suggest a mechanistic link in understanding the molecular processes of viral
      latent-lytic switch.

PMID- 28490593
TI  - Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats
      against Ebola, Influenza, and Other RNA Viruses.
AB  - Bats serve as a reservoir for various, often zoonotic viruses, including
      significant human pathogens such as Ebola and influenza viruses. However, for
      unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight
      control of viral replication by the host innate immune defense might contribute
      to this phenomenon. Transcriptomic studies revealed the presence of the
      interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but
      detailed functional aspects have not been assessed. To provide evidence that bat
      Mx proteins might act as key factors to control viral replication we cloned Mx1
      cDNAs from three bat families, Pteropodidae, Phyllostomidae, and
      Vespertilionidae. Phylogenetically these bat Mx1 genes cluster closely with their
      human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus
      like particles, and virus infections, we determined the antiviral potential of
      the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of
      viruses circulating in bats, including Ebola and influenza A-like viruses. The
      related Thogoto virus, however, which is not known to infect bats, was not
      inhibited by bat Mx1. Further, we provide evidence for positive selection in bat
      Mx1 genes that might explain species-specific antiviral activities of these
      proteins. Together, our data suggest a role for Mx1 in controlling these viruses
      in their bat hosts.IMPORTANCE Bats are a natural reservoir for various viruses
      that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens,
      like Ebola or rabies virus. It has been hypothesized that the interferon system
      might play a key role in controlling viral replication in bats. We speculate that
      the interferon-induced Mx proteins might be key antiviral factors of bats and
      have coevolved with bat-borne viruses. This study evaluated for the first time a
      large set of bat Mx1 proteins spanning three major bat families for their
      antiviral potential, including activity against Ebola virus and bat influenza A
      like virus, and we describe here their phylogenetic relationship, revealing
      patterns of positive selection that suggest a coevolution with viral pathogens.
      By understanding the molecular mechanisms of the innate resistance of bats
      against viral diseases, we might gain important insights into how to prevent and
      fight human zoonotic infections caused by bat-borne viruses.

PMID- 28490594
TI  - Dok-1 and Dok-2 Are Required To Maintain Herpes Simplex Virus 1-Specific CD8+ T
      Cells in a Murine Model of Ocular Infection.
AB  - Dok-1 and Dok-2 negatively regulate responses downstream of several immune
      receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins
      are essential in the formation of memory CD8+ T cells to an exogenous epitope
      expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the
      control of viral infection is unknown. Here, we investigated the role of Dok
      proteins in modulating the immune response against herpes simplex virus 1 (HSV-1)
      in a mouse model of ocular infection. During acute infection, viral titers in the
      eye were similar in wild-type (WT) and Dok-1 and Dok-2 double-knockout (DKO)
      mice, and the percentages of infiltrating leukocytes were similar in DKO and WT
      corneas and trigeminal ganglia (TG). DKO mice exhibited a diminished CD8+ T cell
      response to the immunodominant HSV-1 glycoprotein B (gB) epitope in the spleen
      and draining lymph nodes compared to WT mice during acute infection. Remarkably,
      gB-specific CD8+ T cells almost completely disappeared in the spleens of DKO mice
      during latency, and the reduction of CD8+ effector memory T (Tem) cells was more
      severe than that of CD8+ central memory T (Tcm) cells. The percentage of gB
      specific CD8+ T cells in TG during latency was also dramatically reduced in DKO
      mice; however, they were phenotypically similar to those from WT mice. In ex vivo
      assays, reactivation was detected earlier in TG cultures from infected DKO versus
      WT mice. Thus, Dok-1 and Dok-2 promote survival of gB-specific CD8+ T cells in TG
      latently infected with HSV-1.IMPORTANCE HSV-1 establishes lifelong latency in
      sensory neurons of trigeminal ganglia (TG). In humans, HSV-1 is able to
      sporadically reactivate from latently infected neurons and establish a lytic
      infection at a site to which the neurons project. Most herpetic disease in humans
      is due to reactivation of HSV-1 from latency rather than to primary acute
      infection. CD8+ T cells are thought to play an important role in controlling
      recurrent infections. In this study, we examined the involvement of Dok-1 and Dok
      2 signaling proteins in the control of HSV-1 infection. We provide evidence that
      Dok proteins are required to maintain a CD8+ T cell response against HSV-1 during
      latency-especially CD8+ Tem cells-and that they negatively affect HSV-1
      reactivation from latency. Elucidating Dok-mediated mechanisms involved in the
      control of HSV-1 reactivation from latency might contribute to the development of
      therapeutic strategies to prevent recurrent HSV-1-induced pathology.

PMID- 28490595
TI  - Sensing of HIV-1 Entry Triggers a Type I Interferon Response in Human Primary
      Macrophages.
AB  - Along with CD4+ T lymphocytes, macrophages are a major cellular source of HIV-1
      replication and a potential viral reservoir. Following entry and reverse
      transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid
      limits its cytosolic detection, enabling efficient replication. However, whether
      incoming HIV-1 particles are sensed by macrophages prior to reverse transcription
      remains unclear. Here, we show that HIV-1 triggers a broad expression of
      interferon (IFN)-stimulated genes (ISG) in monocyte-derived macrophages within a
      few hours after infection. This response does not require viral reverse
      transcription or the presence of HIV-1 RNA within particles, but viral fusion is
      essential. This response is elicited by viruses carrying different envelope
      proteins and thus different receptors to proceed for viral entry. Expression of
      ISG in response to viral entry requires TBK1 activity and type I IFNs signaling.
      Remarkably, the ISG response is transient but affects subsequent viral spread.
      Together, our results shed light on an early step of HIV-1 sensing by macrophages
      at the level of entry, which confers an early protection through type I IFN
      signaling and has potential implications in controlling the infection.IMPORTANCE
      HIV infection is restricted to T lymphocytes and macrophages. HIV-1-infected
      macrophages are found in many tissues of infected patients, even under
      antiretroviral therapy, and are considered a viral reservoir. How HIV-1 is
      detected and what type of responses are elicited upon sensing remain in great
      part elusive. The kinetics and localization of the production of cytokines such
      as interferons in response to HIV is of critical importance to understanding how
      the infection and the immune response are established. Our study provides
      evidence that macrophages can detect HIV-1 as soon as it enters the cell.
      Interestingly, this sensing is independent of the presence of viral nucleic acids
      within the particles but requires their fusion with the macrophages. This
      triggers a low interferon response, which activates an antiviral program
      protecting cells against further viral challenge and thus potentially limiting
      the spread of the infection.

PMID- 28490596
TI  - Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis,
      Leading to Retention of the Scaffold Protein and Mislocalization of Membrane
      Associated Entry Proteins.
AB  - The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino
      acid protein with a putative C-terminal transmembrane domain. Previous studies
      with a tetracycline-inducible mutant demonstrated that I2-deficient virions are
      defective in cell entry. The purpose of the present study was to determine the
      step of replication or entry that is affected by loss of the I2 protein.
      Fluorescence microscopy experiments showed that I2 colocalized with a major
      membrane protein of immature and mature virions. We generated a cell line that
      constitutively expressed I2 and allowed construction of the VACV I2L deletion
      mutant vDeltaI2. As anticipated, vDeltaI2 was unable to replicate in cells that
      did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after
      immature virion formation, resulting in the accumulation of dense spherical
      particles instead of brick-shaped mature virions with well-defined core
      structures. The abnormal particles retained the D13 scaffold protein of immature
      virions, were severely deficient in the transmembrane proteins that comprise the
      entry fusion complex (EFC), and had increased amounts of unprocessed membrane and
      core proteins. Total lysates of cells infected with vDeltaI2 also had diminished
      EFC proteins due to instability attributed to their hydrophobicity and failure to
      be inserted into viral membranes. A similar instability of EFC proteins had
      previously been found with unrelated mutants blocked earlier in morphogenesis
      that also accumulated viral membranes retaining the D13 scaffold. We concluded
      that I2 is required for virion morphogenesis, release of the D13 scaffold, and
      the association of EFC proteins with viral membranes.IMPORTANCE Poxviruses
      comprise a large family that infect vertebrates and invertebrates, cause disease
      in both in humans and in wild and domesticated animals, and are being engineered
      as vectors for vaccines and cancer therapy. In addition, investigations of
      poxviruses have provided insights into many aspects of cell biology. The I2
      protein is conserved in all poxviruses that infect vertebrates, suggesting an
      important role. The present study revealed that this protein is essential for
      vaccinia virus morphogenesis and that its absence results in an accumulation of
      deformed virus particles retaining the scaffold protein and deficient in surface
      proteins needed for cell entry.

PMID- 28490597
TI  - Molluscum Contagiosum Virus Protein MC005 Inhibits NF-kappaB Activation by
      Targeting NEMO-Regulated IkappaB Kinase Activation.
AB  - Molluscum contagiosum virus (MCV), the only known extant human-adapted poxvirus,
      causes a long-duration infection characterized by skin lesions that typically
      display an absence of inflammation despite containing high titers of live virus.
      Despite this curious presentation, MCV is very poorly characterized in terms of
      host-pathogen interactions. The absence of inflammation around MCV lesions
      suggests the presence of potent inhibitors of human antiviral immunity and
      inflammation. However, only a small number of MCV immunomodulatory genes have
      been characterized in detail. It is likely that many more remain to be
      discovered, given the density of such sequences in other poxvirus genomes. NF
      kappaB activation occurs in response to both virus-induced pattern recognition
      receptor (PRR) signaling and cellular activation by virus-induced proinflammatory
      cytokines like tumor necrosis factor and interleukin-1. Activated NF-kappaB
      drives cytokine and interferon gene expression, leading to inflammation and virus
      clearance. We report that MC005, which has no orthologs in other poxvirus
      genomes, is a novel inhibitor of PRR- and cytokine-stimulated NF-kappaB
      activation. MC005 inhibited NF-kappaB proximal to the IkappaB kinase (IKK)
      complex, and unbiased affinity purification revealed that MC005 interacts with
      the IKK subunit NEMO (NF-kappaB essential modulator). MC005 binding to NEMO
      prevents the conformational priming of the IKK complex that occurs when NEMO
      binds to ubiquitin chains during pathway activation. These data reveal a novel
      mechanism of poxvirus inhibition of human innate immunity, validate current
      dynamic models of NEMO-dependent IKK complex activation, and further clarify how
      the human-adapted poxvirus MCV can so effectively evade antiviral immunity and
      suppress inflammation to persist in human skin lesions.IMPORTANCE Poxviruses
      adapt to specific hosts over time, evolving and tailoring elegantly precise
      inhibitors of the rate-limiting steps within the signaling pathways that control
      innate immunity and inflammation. These inhibitors reveal new features of the
      antiviral response, clarify existing models of signaling regulation while
      offering potent new tools for approaching therapeutic intervention in
      autoimmunity and inflammatory disease. Molluscum contagiosum virus (MCV) is the
      only known extant poxvirus specifically adapted to human infection and appears
      adept at evading normal human antiviral responses, yet it remains poorly
      characterized. We report the identification of MCV protein MC005 as an inhibitor
      of the pathways leading to the activation of NF-kappaB, an essential regulator of
      innate immunity. Further, identification of the mechanism of inhibition of NF
      kappaB by MC005 confirms current models of the complex way in which NF-kappaB is
      regulated and greatly expands our understanding of how MCV so effectively evades
      human immunity.

PMID- 28490598
TI  - Development of Clade-Specific and Broadly Reactive Live Attenuated Influenza
      Virus Vaccines against Rapidly Evolving H5 Subtype Viruses.
AB  - We have developed pandemic live attenuated influenza vaccines (pLAIVs) against
      clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long
      term immune memory. In 2015, many human infections caused by a new clade (clade
      2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt,
      which prompted updating of the H5N1 pLAIV. We explored two strategies to generate
      suitable pLAIVs. The first approach was to modify the hemagglutinin gene of a
      highly pathogenic wild-type (wt) clade 2.2.1.1 virus, A/Egypt/N03434/2009
      (Egy/09) (H5N1), with its unmodified neuraminidase (NA) gene; this virus was
      designated Egy/09 ca The second approach was to select a low-pathogenicity avian
      influenza H5 virus that elicited antibodies that cross-reacted with a broad range
      of H5 viruses, including the Egypt H5N1 viruses, and contained a novel NA subtype
      for humans. We selected the low-pathogenicity A/duck/Hokkaido/69/2000 (H5N3)
      (dk/Hok/00) virus for this purpose. Both candidate vaccines were attenuated and
      immunogenic in ferrets, inducing antibodies that neutralized homologous and
      heterologous H5 viruses with different degrees of cross-reactivity; Egy/09 ca
      vaccine antisera were more specific for the gs/GD lineage viruses but did not
      neutralize recent North American isolates (clade 2.3.4.4), whereas antisera from
      dk/Hok/69 ca-vaccinated ferrets cross-reacted with clade 2.3.4.4 and 2.2.1
      viruses but not clade 1 or 2.1 viruses. When vaccinated ferrets were challenged
      with homologous and heterologous H5 viruses, challenge virus replication was
      reduced in the respiratory tract. Thus, the two H5 pLAIV candidates are suitable
      for clinical development to protect humans from infection with different clades
      of H5 viruses.IMPORTANCE In response to the continuing evolution of H5N1 avian
      influenza viruses and human infections, new candidate H5 live attenuated vaccines
      were developed by using two different approaches: one targeted a specific
      circulating strain in Egypt, and the other was based on a virus that elicits
      broadly cross-reactive antibodies against a wide range of H5 viruses. Both
      candidate vaccines were immunogenic and exhibited protective efficacy in ferrets.
      Our study permits a comparison of the two approaches, and the data support the
      further development of both vaccine viruses to optimally prepare for the further
      spread of clade 2.2.1 or 2.3.4.4 viruses.

PMID- 28490599
TI  - The phenotype of SDHB germline mutation carriers: a nationwide study.
AB  - OBJECTIVE: Succinate dehydrogenase B subunit (SDHB) gene germline mutations
      predispose to pheochromocytomas, sympathetic paragangliomas, head and neck
      paragangliomas and non-paraganglionic tumors (e.g. renal cell carcinoma,
      gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study
      was to determine phenotypical characteristics of a large Dutch cohort of SDHB
      germline mutation carriers and assess differences in clinical phenotypes related
      to specific SDHB mutations. DESIGN: Retrospective descriptive study. METHODS:
      Retrospective descriptive study in seven academic centers. RESULTS: We included
      194 SDHB mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%)
      relatives. Mean age was 44.8 +/- 16.0 years. Median duration of follow-up was 2.6
      years (range: 0-36). Sixty persons (30.9%) carried the exon 3 deletion and 46
      (23.7%) the c.423 + 1G > A mutation. Fifty-four mutation carriers (27.8%) had one
      or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26
      (13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%)
      developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic
      tumors. At study close, there were 111 (57.2%) unaffected mutation carriers.
      Statistical analyses showed no significant differences in the number and location
      of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas,
      nor in the occurrence of metastatic disease or other tumors between carriers of
      the two founder SDHB mutations (exon 3 deletion vs c.423 + 1G > A). CONCLUSIONS:
      In this nationwide study of disease-affected and unaffected SDHB mutation
      carriers, we observed a lower rate of metastatic disease and a relatively high
      number of head and neck paragangliomas compared with previously reported referral
      based cohorts.

PMID- 28490600
TI  - Something is definitely better than nothing: simple strategies to prevent
      vascular dysfunction.
AB  - Understanding the negative health consequences of a physical inactivity has been
      the topic of much investigation as an alarming number of adults have adopted a
      sedentary lifestyle. With the rise in sedentarism the field of inactivity
      physiology has emerged. The goal of inactivity physiology is to identify the
      impact in inactivity on health and develop strategies that effectively minimize
      the risk of a sedentary lifestyle. Arising from this field is the finding that
      excessive sitting is linked to increased cardiovascular and metabolic disease and
      all-cause mortality. Most importantly, these relationships exist even in
      individuals that are physically active. Clearly, excessive sitting is an
      occupational hazard with significant health consequences. Through a series of
      investigations, including research published this issue of Clinical Science,
      Padilla and colleagues have identified that prolonged sitting evokes vascular
      dysfunction and that this dysfunction is caused by reduced shear stress. This
      commentary highlights this series of investigations and culminates with an
      overview of how prior exercise and standing are effective strategies to
      circumvent vascular dysfunction that is caused by excessive sitting.

PMID- 28490601
TI  - Optimizing mating encounters by sexually dimorphic movements.
AB  - All organisms with sexual reproduction undergo a process of mating, which
      essentially involves the encounter of two individuals belonging to different
      sexes. During mate search, both sexes should mutually optimize their encounters,
      thus raising a question of how they achieve this. Here, we show that a population
      with sexually dimorphic movement patterns achieves the highest individual mating
      success under a limited lifespan. Extensive simulations found and analytical
      approximations corroborated the existence of conditions under which sexual
      dimorphism in the movement patterns (i.e. how diffusively they move) is
      advantageous over sexual monomorphism. Mutual searchers with limited lifespans
      need to balance the speed and accuracy of finding their mates, and dimorphic
      movements can solve this trade-off. We further demonstrate that the sexual
      dimorphism can evolve from an initial sexually monomorphic population. Our
      results emphasize the importance of considering mutual optimization in problems
      of random search.

PMID- 28490602
TI  - Processes on the emergent landscapes of biochemical reaction networks and
      heterogeneous cell population dynamics: differentiation in living matters.
AB  - The notion of an attractor has been widely employed in thinking about the
      nonlinear dynamics of organisms and biological phenomena as systems and as
      processes. The notion of a landscape with valleys and mountains encoding multiple
      attractors, however, has a rigorous foundation only for closed, thermodynamically
      non-driven, chemical systems, such as a protein. Recent advances in the theory of
      nonlinear stochastic dynamical systems and its applications to mesoscopic
      reaction networks, one reaction at a time, have provided a new basis for a
      landscape of open, driven biochemical reaction systems under sustained chemostat.
      The theory is equally applicable not only to intracellular dynamics of
      biochemical regulatory networks within an individual cell but also to tissue
      dynamics of heterogeneous interacting cell populations. The landscape for an
      individual cell, applicable to a population of isogenic non-interacting cells
      under the same environmental conditions, is defined on the counting space of
      intracellular chemical compositions x = (x1,x2, ... ,xN ) in a cell, where xl is
      the concentration of the lth biochemical species. Equivalently, for heterogeneous
      cell population dynamics xl is the number density of cells of the lth cell type.
      One of the insights derived from the landscape perspective is that the life
      history of an individual organism, which occurs on the hillsides of a landscape,
      is nearly deterministic and 'programmed', while population-wise an asynchronous
      non-equilibrium steady state resides mostly in the lowlands of the landscape. We
      argue that a dynamic 'blue-sky' bifurcation, as a representation of Waddington's
      landscape, is a more robust mechanism for a cell fate decision and subsequent
      differentiation than the widely pictured pitch-fork bifurcation. We revisit, in
      terms of the chemostatic driving forces upon active, living matter, the notions
      of near-equilibrium thermodynamic branches versus far-from-equilibrium states.
      The emergent landscape perspective permits a quantitative discussion of a wide
      range of biological phenomena as nonlinear, stochastic dynamics.

PMID- 28490604
TI  - The evolution of lossy compression.
AB  - In complex environments, there are costs to both ignorance and perception. An
      organism needs to track fitness-relevant information about its world, but the
      more information it tracks, the more resources it must devote to perception. As a
      first step towards a general understanding of this trade-off, we use a tool from
      information theory, rate-distortion theory, to study large, unstructured
      environments with fixed, randomly drawn penalties for stimuli confusion
      ('distortions'). We identify two distinct regimes for organisms in these
      environments: a high-fidelity regime where perceptual costs grow linearly with
      environmental complexity, and a low-fidelity regime where perceptual costs are,
      remarkably, independent of the number of environmental states. This suggests that
      in environments of rapidly increasing complexity, well-adapted organisms will
      find themselves able to make, just barely, the most subtle distinctions in their
      environment.

PMID- 28490603
TI  - Inferring single-cell behaviour from large-scale epithelial sheet migration
      patterns.
AB  - Cell migration plays an important role in a wide variety of biological processes
      and can incorporate both individual cell motion and collective behaviour. The
      emergent properties of collective migration are receiving increasing attention as
      collective motion's role in diseases such as metastatic cancer becomes clear.
      Yet, how individual cell behaviour influences large-scale, multi-cell collective
      motion remains unclear. In this study, we provide insight into the mechanisms
      behind collective migration by studying cell migration in a spreading monolayer
      of epithelial MCF10A cells. We quantify migration using particle image
      velocimetry and find that cell groups have features of motion that span multiple
      length scales. Comparing our experimental results to a model of collective cell
      migration, we find that cell migration within the monolayer can be affected in
      qualitatively different ways by cell motion at the boundary, yet it is not
      necessary to introduce leader cells at the boundary or specify other large-scale
      features to recapitulate this large-scale phenotype in simulations. Instead, in
      our model, collective motion can be enhanced by increasing the overall activity
      of the cells or by giving the cells a stronger coupling between their motion and
      polarity. This suggests that investigating the activity and polarity persistence
      of individual cells will add insight into the collective migration phenotypes
      observed during development and disease.

PMID- 28490605
TI  - Adhesion modulation using glue droplet spreading in spider capture silk.
AB  - Orb web spiders use sticky capture spiral silk to retain prey in webs. Capture
      spiral silk is composed of an axial fibre of flagelliform silk covered with glue
      droplets that are arranged in a beads-on-a-string morphology that allows multiple
      droplets to simultaneously extend and resist pull off. Previous studies showed
      that the adhesion of capture silk is responsive to environmental humidity,
      increasing up to an optimum humidity that varied among different spider species.
      The maximum adhesion was hypothesized to occur when the viscoelasticity of the
      glue optimized contributions from glue spreading and bulk cohesion. In this
      study, we show how glue droplet shape during peeling contributes significantly to
      capture silk adhesion. Both overspreading and underspreading of glue droplets
      reduces adhesion through changes in crack propagation and failure regime.
      Understanding the mechanism of stimuli-responsive adhesion of spider capture silk
      will lead to new designs for smarter adhesives.

PMID- 28490607
TI  - Reviewers in 2016.

PMID- 28490606
TI  - Comparison of 10 murine models reveals a distinct biomechanical phenotype in
      thoracic aortic aneurysms.
AB  - Thoracic aortic aneurysms are life-threatening lesions that afflict young and old
      individuals alike. They frequently associate with genetic mutations and are
      characterized by reduced elastic fibre integrity, dysfunctional smooth muscle
      cells, improperly remodelled collagen and pooled mucoid material. There is a
      pressing need to understand better the compromised structural integrity of the
      aorta that results from these genetic mutations and renders the wall vulnerable
      to dilatation, dissection or rupture. In this paper, we compare the biaxial
      mechanical properties of the ascending aorta from 10 murine models: wild-type
      controls, acute elastase-treated, and eight models with genetic mutations
      affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal
      proteins, or intracellular signalling molecules. Collectively, our data for these
      diverse mouse models suggest that reduced mechanical functionality, as indicated
      by a decreased elastic energy storage capability or reduced distensibility, does
      not predispose to aneurysms. Rather, despite normal or lower than normal
      circumferential and axial wall stresses, it appears that intramural cells in the
      ascending aorta of mice prone to aneurysms are unable to maintain or restore the
      intrinsic circumferential material stiffness, which may render the wall
      biomechanically vulnerable to continued dilatation and possible rupture. This
      finding is consistent with an underlying dysfunctional mechanosensing or
      mechanoregulation of the extracellular matrix, which normally endows the wall
      with both appropriate compliance and sufficient strength.

PMID- 28490608
TI  - Expanding the use of flow diverters beyond their initial indication: treatment of
      small unruptured aneurysms.
AB  - BACKGROUND: Experience with the endovascular treatment of unruptured small
      intracranial aneurysms by flow diverter devices is still limited. OBJECTIVE: To
      assess the safety and efficacy of the SILK flow diverter (SFD) in the treatment
      of small unruptured cerebral aneurysms (<10 mm). METHODS: We performed a
      retrospective review of a prospectively maintained database of patients treated
      with a SFD between July 2008 and December 2013 at 4 institutions in Spain to
      identify all patients with small unruptured aneurysms (<10 mm). Data for patient
      demographics, aneurysm characteristics, and technical procedures were analyzed.
      Angiographic and clinical findings were recorded during the procedure and at 6-
      and 12-month follow-ups. RESULTS: A total of 109 small aneurysms were treated
      with a SFD in 104 patients (78 women; 26 men; mean, median, and range of age:
      55.2, 57.1, and 19-80 years, respectively). A total of 60 patients were
      asymptomatic (57.7%). All except 7 aneurysms (6.4%) arose from the anterior
      circulation. The mean size of the aneurysms was 4.7+/-1.9 mm. At 6 months, the
      neuromorbidity and neuromortality rates were 2.9% and 0.9%, respectively. Imaging
      at the 12-month follow-up showed complete occlusion, neck remnants, and residual
      aneurysm in 88.5% (69/78), 7.7% (6/78), and 3.3% (3/78) of cases, respectively.
      No delayed hemorrhage occurred. CONCLUSIONS: The findings suggest that the
      indications for SFD can be safely extended to small intracranial aneurysms.

PMID- 28490611
TI  - Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)
      associated polyposis.
AB  - BACKGROUND: Screening of patients with familial adenomatous polyposis (FAP) have
      led to a substantial reduction in mortality due to colorectal cancer (CRC).
      Recent guidelines suggest that surveillance of non-intestinal malignancies should
      also be considered in those patients. However, the value of these surveillance
      programmes is unknown. The aims of this study were (1) to assess the occurrence
      of extracolonic malignancies in a large series of adenomatous polyposis coli
      (APC) mutation carriers and (2) to evaluate the causes of death. METHODS: All APC
      mutation carriers were selected from the Dutch polyposis registry. Data on causes
      of death were collected. Pathology reports were retrieved from the Dutch
      Pathology Registry. RESULTS: A total of 85 extracolonic malignancies were
      diagnosed in 74 of 582 APC mutation carriers. Duodenal and skin cancers were the
      most prevalent cancers. Thyroid cancer was observed in only 1.5% of the cases.
      The main cause of death was cancer (59% of all deaths), with 42% due to CRC and
      21% due to duodenal cancer. One patient died from thyroid cancer. The second and
      third most common causes of death were cardiovascular disease (13% of all deaths)
      and desmoid tumours (11% of all deaths), respectively. CONCLUSION: Extending
      surveillance programmes to other cancers will not contribute significantly to the
      survival of patients with FAP.

PMID- 28490610
TI  - Mechanisms of Insulin Resistance in Primary and Secondary Nonalcoholic Fatty
      Liver.
AB  - Nonalcoholic fatty liver disease is associated with hepatic insulin resistance
      and may result primarily from increased hepatic de novo lipogenesis (PRIM) or
      secondarily from adipose tissue lipolysis (SEC). We studied mice with hepatocyte-
      or adipocyte-specific SREBP-1c overexpression as models of PRIM and SEC. PRIM
      mice featured increased lipogenic gene expression in the liver and adipose
      tissue. Their selective, liver-specific insulin resistance was associated with
      increased C18:1-diacylglycerol content and protein kinase Cepsilon translocation.
      SEC mice had decreased lipogenesis mediated by hepatic cholesterol responsive
      element-binding protein and featured portal/lobular inflammation along with
      total, whole-body insulin resistance. Hepatic mitochondrial respiration
      transiently increased and declined with aging along with higher muscle reactive
      oxygen species production. In conclusion, hepatic insulin resistance originates
      from lipotoxicity but not from lower mitochondrial capacity, which can even
      transiently adapt to increased peripheral lipolysis. Peripheral insulin
      resistance is prevented during increased hepatic lipogenesis only if adipose
      tissue lipid storage capacity is preserved.

PMID- 28490612
TI  - Pathology update to the Manchester Scoring System based on testing in over 4000
      families.
AB  - BACKGROUND: While the requirement for thresholds for testing for mutations in
      BRCA1/2 is being questioned, they are likely to remain for individuals unaffected
      by a relevant cancer. It is still useful to provide pretesting likelihoods, but
      models need to take into account tumour pathology. METHODS: The Manchester
      Scoring System (MSS) is a well-used, simple, paper-based model for assessing
      carrier probability that already incorporates pathology data. We have used
      mutation testing data from 4115 unrelated samples from affected non-Jewish
      individuals alongside tumour pathology to further refine the scoring system.
      RESULTS: Adding additional points for high-grade serous ovarian cancer <60
      (HGSOC=+2) and adding grade score to those with triple-negative breast cancer,
      while reducing the score for those with HER2+ breast cancer (-6), resulted in
      significantly improved sensitivity and minor improvements in specificity to the
      MSS. Sporadic HGSOC <60 years thus reached a score of 15-19 points within the 10%
      grouping consistent with the 15/113-13.2% that were identified with a BRCA1/2
      pathogenic variant. Validation in a population series of ovarian cancer from
      Cambridge showed high sensitivity at the 10% threshold 15/17 (88.2%).
      CONCLUSIONS: The new pathology-adjusted Manchester score MSS3 appears to provide
      an effective and simple-to-use estimate of the 10% and 20% thresholds for BRCA1/2
      likelihood. For unaffected individuals, the 20-point (20%) threshold in their
      affected first-degree relative can be used to determine eligibility at the 10%
      threshold.

PMID- 28490609
TI  - A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin
      Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants.
AB  - Understanding the physiological mechanisms by which common variants predispose to
      type 2 diabetes requires large studies with detailed measures of insulin
      secretion and sensitivity. Here we performed the largest genome-wide association
      study of first-phase insulin secretion, as measured by intravenous glucose
      tolerance tests, using up to 5,567 individuals without diabetes from 10 studies.
      We aimed to refine the mechanisms of 178 known associations between common
      variants and glycemic traits and identify new loci. Thirty type 2 diabetes or
      fasting glucose-raising alleles were associated with a measure of first-phase
      insulin secretion at P < 0.05 and provided new evidence, or the strongest
      evidence yet, that insulin secretion, intrinsic to the islet cells, is a key
      mechanism underlying the associations at the HNF1A, IGF2BP2, KCNQ1, HNF1B,
      VPS13C/C2CD4A, FAF1, PTPRD, AP3S2, KCNK16, MAEA, LPP, WFS1, and TMPRSS6 loci. The
      fasting glucose-raising allele near PDX1, a known key insulin transcription
      factor, was strongly associated with lower first-phase insulin secretion but has
      no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at
      TCF7L2 was associated with a stronger effect on peak insulin response than on C
      peptide-based insulin secretion rate, suggesting a possible additional role in
      hepatic insulin clearance or insulin processing. In summary, our study provides
      further insight into the mechanisms by which common genetic variation influences
      type 2 diabetes risk and glycemic traits.

PMID- 28490614
TI  - Value in cardiovascular care.
AB  - Healthcare value, defined as health outcomes achieved relative to the costs of
      care, has been proposed as a unifying approach to measure improvements in the
      quality and affordability of healthcare. Although value is of increasing interest
      to payers, many providers remain unfamiliar with how value differs from other
      approaches to the comparison of cost and outcomes (ie, cost-effectiveness
      analysis). While cost-effectiveness studies can be used by policy makers and
      payers to inform decisions about coverage and reimbursement for new therapies,
      the assessment of healthcare can guide improvements in the delivery of healthcare
      to achieve better outcomes at lower cost. Comparison on value allows for the
      identification of healthcare delivery organisations or care delivery settings
      where patient outcomes have been optimised at a lower cost. Gaps remain in the
      measurement of healthcare value, particularly as it relates to patient-reported
      health status (symptoms, functional status and health-related quality of life).
      The use of technology platforms that capture health status measures with minimal
      disruption to clinical workflow (ie, web portals, automated telephonic systems
      and tablets to facilitate capture outside of in-person clinical interaction) is
      facilitating use of health status measures to improve clinical care and optimise
      patient outcomes. Furthermore, the use of a value framework has catalysed quality
      improvement efforts and research to seek better patient outcomes at lower cost.

PMID- 28490613
TI  - The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and
      ovarian cancer risk estimation and recommendations for clinical management from
      the ENIGMA consortium.
AB  - BACKGROUND: We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln
      (R1699Q) was associated with an intermediate risk of breast cancer (BC) and
      ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q
      carriers in a larger cohort, including follow-up of previously studied families,
      to further define cancer risks and to propose adjusted clinical management of
      female BRCA1*R1699Q carriers. METHODS: Data were collected from 129 BRCA1*R1699Q
      families ascertained internationally by ENIGMA (Evidence-based Network for the
      Interpretation of Germline Mutant Alleles) consortium members. A modified
      segregation analysis was used to calculate BC and OC risks. Relative risks were
      calculated under both monogenic model and major gene plus polygenic model
      assumptions. RESULTS: In this cohort the cumulative risk of BC and OC by age 70
      years was 20% and 6%, respectively. The relative risk for developing cancer was
      higher when using a model that included the effects of both the R1699Q variant
      and a residual polygenic component compared with monogenic model (for BC 3.67 vs
      2.83, and for OC 6.41 vs 5.83). CONCLUSION: Our results confirm that BRCA1*R1699Q
      confers an intermediate risk for BC and OC. Breast surveillance for female
      carriers based on mammogram annually from age 40 is advised. Bilateral salpingo
      oophorectomy should be considered based on family history.

PMID- 28490615
TI  - Contemporary natural history of bicuspid aortic valve disease: a systematic
      review.
AB  - We performed a systematic review of the current state of the literature regarding
      the natural history and outcomes of bicuspid aortic valve (BAV). PubMed and the
      reference lists of the included articles were searched for relevant studies
      reporting on longitudinal follow-up of BAV cohorts (mean follow-up >=2 years).
      Studies limited to patients undergoing surgical interventions were excluded. 13
      studies (11 502 patients with 2-16 years of follow-up) met the inclusion
      criteria. There was a bimodal age distribution (30-40 vs >=50 years), with a 3:1
      male to female ratio. Complications included moderate to severe aortic
      regurgitation (prevalence 13%-30%), moderate to severe aortic stenosis (12%-37%),
      infective endocarditis (2%-5%) and aortic dilatation (20%-40%). Aortic dissection
      or rupture was rare, occurring in 38 patients (0.4%, 27/6446 in native BAV and
      11/2232 in post). With current aggressive surveillance and prophylactic surgical
      interventions, survival in three out of four studies was similar to that of a
      matched general population. In this systematic review, valvular dysfunction
      warranting surgical intervention in patients with BAV were common, aortic
      dissection was rare and, with the current management approach, survival was
      similar to that of the general population.

PMID- 28490616
TI  - Integrated care in atrial fibrillation: a systematic review and meta-analysis.
AB  - OBJECTIVE: Atrial fibrillation (AF) is an emerging global epidemic associated
      with significant morbidity and mortality. Whilst other chronic cardiovascular
      conditions have demonstrated enhanced patient outcomes from coordinated systems
      of care, the use of this approach in AF is a comparatively new concept. Recent
      evidence has suggested that the integrated care approach may be of benefit in the
      AF population, yet has not been widely implemented in routine clinical practice.
      We sought to undertake a systematic review and meta-analysis to evaluate the
      impact of integrated care approaches to care delivery in the AF population on
      outcomes including mortality, hospitalisations, emergency department visits,
      cerebrovascular events and patient-reported outcomes. METHODS: PubMed, Embase and
      CINAHL databases were searched until February 2016 to identify papers addressing
      the impact of integrated care in the AF population. Three studies, with a total
      study population of 1383, were identified that compared integrated care
      approaches with usual care in AF populations. RESULTS: Use of this approach was
      associated with a reduction in all-cause mortality (OR 0.51, 95% CI 0.32 to 0.80,
      p=0.003) and cardiovascular hospitalisations (OR 0.58, 95% CI 0.44 to 0.77,
      p=0.0002) but did not significantly impact on AF-related hospitalisations (OR
      0.82, 95% CI 0.56 to 1.19, p=0.29) or cerebrovascular events (OR 1.00, 95% CI
      0.48 to 2.09, p=1.00). CONCLUSIONS: The use of the integrated care approach in AF
      is associated with reduced cardiovascular hospitalisations and all-cause
      mortality. Further research is needed to identify optimal settings, methods and
      components of delivering integrated care to the burgeoning AF population.

PMID- 28490617
TI  - Systemic inflammation as a novel QT-prolonging risk factor in patients with
      torsades de pointes.
AB  - OBJECTIVE: Increasing evidence indicates systemic inflammation as a new potential
      cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in
      cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening
      polymorphic ventricular tachycardia occurring in patients with LQTS, usually when
      multiple QT-prolonging factors are simultaneously present. Since classical risk
      factors cannot fully explain TdP events in a number of patients, we hypothesised
      that systemic inflammation may represent a currently overlooked risk factor
      contributing to TdP development in the general population. METHODS: Forty
      consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled
      and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines
      (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL
      1)) were compared with patients with active rheumatoid arthritis (RA),
      comorbidity or healthy controls. An additional 46 patients with different
      inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12;
      others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled,
      and corrected QT (QTc) and cytokine levels were measured during active disease
      and after a CRP decrease of >75% subsequent to therapy. RESULTS: In the TdP
      cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a
      definite inflammatory disease identifiable in 18/40 cases (acute infections,
      n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but
      not TNFalpha and IL-1, was ~15-20 times higher than in controls, and comparable
      to RA patients. In the inflammatory cohort, where QTc prolongation was common
      (mean values: 456.6+/-30.9 ms), CRP reduction was associated with IL-6 level
      decrease and significant QTc shortening (-22.3 ms). CONCLUSION: The data are
      first to show that systemic inflammation via elevated IL-6 levels may represent a
      novel QT-prolonging risk factor contributing to TdP occurrence in the presence of
      other classical risk factors. If confirmed, this could open new avenues in
      antiarrhythmic therapy.

PMID- 28490618
TI  - 21-year-old with exertional dyspnoea.

PMID- 28490620
TI  - Physical activity evaluation in children with congenital heart disease.
AB  - Significant advances in the management of children with congenital heart disease
      (CHD) have resulted in marked improvements in survival and life expectancy. Thus,
      there is an increased emphasis on promoting physical activity to optimise healthy
      development and long-term cardiovascular health. Evaluation of physical activity
      levels as part of ongoing clinical care is recommended to facilitate physical
      activity counselling and/or exercise prescription. Physical activity is a complex
      health behaviour that is challenging to evaluate. We provide an overview of
      techniques for measuring physical activity in children with CHD with a focus on
      how to do this in the clinical context. Accelerometers are devices that
      objectively assess intensity and duration of physical activity under free living
      conditions. They enable evaluation against physical activity guidelines, but are
      costly and require advanced technical expertise. Pedometers are a simple-to-use
      and cost-effective alternative, but an outcome metric of daily step count limits
      classification against guidelines. Commercial wearable activity trackers offer an
      appealing user experience and can provide valid estimates in children.
      Furthermore, activity trackers enable remote monitoring of physical activity
      levels, which may facilitate exercise prescription and activity counselling.
      Questionnaires are the most cost-effective and time-effective method, but recall
      error in younger children is a consideration. Routine exercise testing in
      children with CHD provides important insight into functional status but should
      not be viewed as a proxy measure of habitual physical activity. Understanding the
      spectrum and role of physical activity measurement tools is important for
      clinicians focused on optimising cardiovascular health in children with CHD.

PMID- 28490619
TI  - Capacity for diagnosis and treatment of heart failure in sub-Saharan Africa.
AB  - OBJECTIVE: Heart failure is a major cause of disease burden in sub-Saharan Africa
      (SSA). There is an urgent need for better strategies for heart failure management
      in this region. However, there is little information on the capacity to diagnose
      and treat heart failure in SSA. We aim to provide a better understanding of the
      capacity to diagnose and treat heart failure in Kenya and Uganda to inform policy
      planning and interventions. METHODS: We analysed data from a nationally
      representative survey of health facilities in Kenya and Uganda (197 health
      facilities in Uganda and 143 in Kenya). We report on the availability of cardiac
      diagnostic technologies and select medications for heart failure (beta-blockers,
      ACE inhibitors and furosemide). Facility-level data were analysed by country and
      platform type (hospital vs ambulatory facilities). RESULTS: Functional and
      staffed radiography, ultrasound and ECG were available in less than half of
      hospitals in Kenya and Uganda combined. Of the hospitals surveyed, 49% of Kenyan
      and 77% of Ugandan hospitals reported availability of the heart failure
      medication package. ACE inhibitors were only available in 51% of Kenyan and 79%
      of Ugandan hospitals. Almost one-third of the hospitals in each country had a
      stock-out of at least one of the medication classes in the prior quarter.
      CONCLUSIONS: Few facilities in Kenya and Uganda were prepared to diagnose and
      manage heart failure. Medication shortages and stock-outs were common. Our
      findings call for increased investment in cardiac care to reduce the growing
      burden of heart failure.

PMID- 28490621
TI  - Plasma 7-ketocholesterol levels and the risk of incident cardiovascular events.
AB  - OBJECTIVE: 7-Ketocholesterol (7-KC), a major oxidation product of cholesterol, is
      found in human atherosclerotic plaque and more atherogenic than cholesterol in
      animal models. This study was designed to investigate the association of plasma 7
      KC level with the incident cardiovascular disease (CVD) events in general
      population. METHODS: We measured plasma 7-KC concentrations at baseline in 1944
      participants free from CVD in a community-based cohort study. The primary
      endpoint was incident of a major adverse cardiovascular event. A Cox proportional
      hazards model was used to calculate the HRs with 95% CI. RESULTS: A total of 101
      incident CVD events were recorded during the 5.2 year median follow-up. The
      baseline plasma 7-KC levels were associated with a higher risk of incident CVD
      events; compared with quartile 1, participants in quartile 4 had an unadjusted HR
      of 2.38 (2.03-2.85, p<0.001) and an adjusted HR of 1.70 (1.45-1.91, p=0.004)
      after adjusting for traditional risk factors. Plasma 7-KC levels improved all of
      the metrics of discrimination and reclassification when added to the intima-media
      thickness (C-statistic: p=0.002; net reclassification improvement (NRI): p<0.001;
      integrated discrimination improvement (IDI): p<0.001), family history of
      myocardial infarction (C-statistic: p=0.011; NRI: p=0.004; IDI: p=0.003) and
      elevated high-sensitivity C reactive protein (C-statistic: p=0.008; NRI: p=0.015;
      IDI: p=0.009). CONCLUSIONS: Elevated plasma 7-KC levels are associated with the
      incident CVD events in a population-based cohort. Further studies are needed to
      confirm this observation.

PMID- 28490622
TI  - Mutualistic strategies minimize coextinction in plant-disperser networks.
AB  - The global decline of mutualists such as pollinators and seed dispersers may
      cause negative direct and indirect impacts on biodiversity. Mutualistic network
      models used to understand the stability of mutualistic systems indicate that
      species with low partner diversity are most vulnerable to coextinction following
      mutualism disruption. However, existing models have not considered how species
      vary in their dependence on mutualistic interactions for reproduction or
      survival, overlooking the potential influence of this variation on species'
      coextinction vulnerability and on network stability. Using global databases and
      field experiments focused on the seed dispersal mutualism, we found that plants
      and animals that depend heavily on mutualistic interactions have higher partner
      diversity. Under simulated network disruption, this empirical relationship
      strongly reduced coextinction because the species most likely to lose mutualists
      depend least on their mutualists. The pattern also reduced the importance of
      network structure for stability; nested network structure had little effect on
      coextinction after simulations incorporated the empirically derived relationship
      between partner diversity and mutualistic dependence. Our results highlight a
      previously unknown source of stability in mutualistic networks and suggest that
      differences among species in their mutualistic strategy, rather than network
      structure, primarily accounts for stability in mutualistic communities.

PMID- 28490623
TI  - Genetics-based interactions of foundation species affect community diversity,
      stability and network structure.
AB  - We examined the hypothesis that genetics-based interactions between strongly
      interacting foundation species, the tree Populus angustifolia and the aphid
      Pemphigus betae, affect arthropod community diversity, stability and species
      interaction networks of which little is known. In a 2-year experimental
      manipulation of the tree and its aphid herbivore four major findings emerged: (i)
      the interactions of these two species determined the composition of an arthropod
      community of 139 species; (ii) both tree genotype and aphid presence
      significantly predicted community diversity; (iii) the presence of aphids on
      genetically susceptible trees increased the stability of arthropod communities
      across years; and (iv) the experimental removal of aphids affected community
      network structure (network degree, modularity and tree genotype contribution to
      modularity). These findings demonstrate that the interactions of foundation
      species are genetically based, which in turn significantly contributes to
      community diversity, stability and species interaction networks. These
      experiments provide an important step in understanding the evolution of Darwin's
      'entangled bank', a metaphor that characterizes the complexity and
      interconnectedness of communities in the wild.

PMID- 28490624
TI  - Removal of an apex predator initiates a trophic cascade that extends from
      herbivores to vegetation and the soil nutrient pool.
AB  - It is widely assumed that organisms at low trophic levels, particularly microbes
      and plants, are essential to basic services in ecosystems, such as nutrient
      cycling. In theory, apex predators' effects on ecosystems could extend to
      nutrient cycling and the soil nutrient pool by influencing the intensity and
      spatial organization of herbivory. Here, we take advantage of a long-term
      manipulation of dingo abundance across Australia's dingo-proof fence in the
      Strzelecki Desert to investigate the effects that removal of an apex predator has
      on herbivore abundance, vegetation and the soil nutrient pool. Results showed
      that kangaroos were more abundant where dingoes were rare, and effects of
      kangaroo exclusion on vegetation, and total carbon, total nitrogen and available
      phosphorus in the soil were marked where dingoes were rare, but negligible where
      dingoes were common. By showing that a trophic cascade resulting from an apex
      predator's lethal effects on herbivores extends to the soil nutrient pool, we
      demonstrate a hitherto unappreciated pathway via which predators can influence
      nutrient dynamics. A key implication of our study is the vast spatial scale
      across which apex predators' effects on herbivore populations operate and, in
      turn, effects on the soil nutrient pool and ecosystem productivity could become
      manifest.

PMID- 28490625
TI  - Nonlinear trade-offs allow the cooperation game to evolve from Prisoner's Dilemma
      to Snowdrift.
AB  - The existence of cooperation, or the production of public goods, is an
      evolutionary problem. Cooperation is not favoured because the Prisoner's Dilemma
      (PD) game drives cooperators to extinction. We have re-analysed this problem by
      using RNA viruses to motivate a model for the evolution of cooperation. Gene
      products are the public goods and group size is the number of virions co
      infecting the same host cell. Our results show that if the trade-off between
      replication and production of gene products is linear, PD is observed. However,
      if the trade-off is nonlinear, the viruses evolve into separate lineages of ultra
      defectors and ultra-cooperators as group size is increased. The nonlinearity was
      justified by the existence of real viral ultra-defectors, known as defective
      interfering particles, which gain a nonlinear advantage by being smaller. The
      evolution of ultra-defectors and ultra-cooperators creates the Snowdrift game,
      which promotes high-level production of public goods.

PMID- 28490626
TI  - Minimal variation in eutherian brain growth rates during fetal neurogenesis.
AB  - A central question in the evolution of brain development is whether species
      differ in rates of brain growth during fetal neurogenesis. Studies of neonatal
      data have found allometric evidence for brain growth rate differences according
      to physiological variables such as relative metabolism and placental
      invasiveness, but these findings have not been tested against fetal data
      directly. Here, we measure rates of exponential brain growth acceleration in 10
      eutherian mammals, two marsupials, and two birds. Eutherian brain acceleration
      exhibits minimal variation relative to body and visceral organ growth, varies
      independently of correlated growth patterns in other organs, and is unrelated to
      proposed physiological constraints such as metabolic rate or placental
      invasiveness. Brain growth rates in two birds overlap with eutherian variation,
      while marsupial brain growth is exceptionally slow. Peak brain growth velocity is
      linked in time with forebrain myelination and eye opening, reliably separates
      altricial species born before it from precocial species born afterwards, and is
      an excellent predictor of adult brain size (r2 = 0.98). Species with faster body
      growth exhibit larger relative brain size in early ontogeny, while brain growth
      is unrelated to allometric measures. These findings indicate a surprising
      conservation of brain growth rates during fetal neurogenesis in eutherian
      mammals, clarify sources of variation in neonatal brain size, and suggest that
      slow body growth rates cause species to be more encephalized at birth.

PMID- 28490627
TI  - Concerted and mosaic evolution of functional modules in songbird brains.
AB  - Vertebrate brains differ in overall size, composition and functional capacities,
      but the evolutionary processes linking these traits are unclear. Two leading
      models offer opposing views: the concerted model ascribes major dimensions of
      covariation in brain structures to developmental events, whereas the mosaic model
      relates divergent structures to functional capabilities. The models are often
      cast as incompatible, but they must be unified to explain how adaptive changes in
      brain structure arise from pre-existing architectures and developmental
      mechanisms. Here we show that variation in the sizes of discrete neural systems
      in songbirds, a species-rich group exhibiting diverse behavioural and ecological
      specializations, supports major elements of both models. In accordance with the
      concerted model, most variation in nucleus volumes is shared across functional
      domains and allometry is related to developmental sequence. Per the mosaic model,
      residual variation in nucleus volumes is correlated within functional systems and
      predicts specific behavioural capabilities. These comparisons indicate that
      oscine brains evolved primarily as a coordinated whole but also experienced
      significant, independent modifications to dedicated systems from specific
      selection pressures. Finally, patterns of covariation between species and brain
      areas hint at underlying developmental mechanisms.

PMID- 28490629
TI  - Pharmacological targeting of RAD6 enzyme-mediated translesion synthesis overcomes
      resistance to platinum-based drugs.
AB  - Platinum drug-induced cross-link repair requires the concerted activities of
      translesion synthesis (TLS), Fanconi anemia (FA), and homologous recombination
      repair pathways. The E2 ubiquitin-conjugating enzyme RAD6 is essential for TLS.
      Here, we show that RAD6 plays a universal role in platinum-based drug tolerance.
      Using a novel RAD6-selective small-molecule inhibitor (SMI#9) targeting the RAD6
      catalytic site, we demonstrate that SMI#9 potentiates the sensitivities of cancer
      cells with innate or acquired cisplatin or oxaliplatin resistance. 5
      Iododeoxyuridine/5-chlorodeoxyuridine pulse-labeling experiments showed that RAD6
      is necessary for overcoming cisplatin-induced replication fork stalling, as
      replication-restart was impaired in both SMI#9-pretreated and RAD6B-silenced
      cells. Consistent with the role of RAD6/TLS in late-S phase, SMI#9-induced DNA
      replication inhibition occurred preferentially in mid/late-S phase. The
      compromised DNA repair and chemosensitization induced by SMI#9 or RAD6B depletion
      were associated with decreased platinum drug-induced proliferating cell nuclear
      antigen (PCNA) and FANCD2 monoubiquitinations (surrogate markers of TLS and FA
      pathway activation, respectively) and with attenuated FANCD2, RAD6, gammaH2AX,
      and POL eta foci formation and cisplatin-adduct removal. SMI#9 pretreatment
      synergistically increased cisplatin inhibition of MDA-MB-231 triple-negative
      breast cancer cell proliferation and tumor growth. Using an isogenic HCT116 colon
      cancer model of oxaliplatin resistance, we further show that gammaH2AX and
      monoubiquitinated PCNA and FANCD2 are constitutively up-regulated in oxaliplatin
      resistant HCT116 (HCT116-OxR) cells and that gammaH2AX, PCNA, and FANCD2
      monoubiquitinations are induced by oxaliplatin in parental HCT116 cells. SMI#9
      pretreatment sensitized HCT116-OxR cells to oxaliplatin. These data deepen
      insights into the vital role of RAD6/TLS in platinum drug tolerance and reveal
      clinical benefits of targeting RAD6 with SMI#9 for managing chemoresistant
      cancers.

PMID- 28490630
TI  - Understanding phospholipid function: Why are there so many lipids?
AB  - In the 1970s, phospholipids were still considered mere building blocks of the
      membrane lipid bilayer, but the subsequent realization that phospholipids could
      also serve as second messengers brought new interest to the field. My own passion
      for the unique amphipathic properties of lipids led me to seek other, non
      signaling functions for phospholipids, particularly in their interactions with
      membrane proteins. This seemed to be the last frontier in protein chemistry and
      enzymology to be conquered. I was fortunate to find my way to Eugene Kennedy's
      laboratory, where both membrane proteins and phospholipids were the foci of
      study, thus providing a jumping-off point for advancing our fundamental
      understanding of lipid synthesis, membrane protein biosynthesis, phospholipid and
      membrane protein trafficking, and the cellular roles of phospholipids. After
      purifying and characterizing enzymes of phospholipid biosynthesis in Escherichia
      coli and cloning of several of the genes encoding these enzymes in E. coli and
      Saccharomyces cerevisiae, I was in a position to alter phospholipid composition
      in a systematic manner during the cell cycle in these microorganisms. My group
      was able to establish, contrary to common assumption (derived from the fact that
      membrane proteins retain activity in detergent extracts) that phospholipid
      environment is a strong determining factor in the function of membrane proteins.
      We showed that molecular genetic alterations in membrane lipid composition result
      in many phenotypes, and uncovered direct lipid-protein interactions that govern
      dynamic structural and functional properties of membrane proteins. Here I present
      my personal "reflections" on how our understanding of phospholipid functions has
      evolved.

PMID- 28490632
TI  - Cell death-inducing DNA fragmentation factor A-like effector A and fat-specific
      protein 27beta coordinately control lipid droplet size in brown adipocytes.
AB  - Adipose tissue stores neutral lipids and is a major metabolic organ involved in
      regulating whole-body energy homeostasis. Triacylglycerol is stored as unilocular
      large lipid droplets (LDs) in white adipocytes and as multilocular small LDs in
      brown adipocytes. Proteins of the cell death-inducing DNA fragmentation factor A
      like effector (Cide) family include CideA, CideB, and fat-specific protein of 27
      (FSP27). Of these, FSP27 has been shown to play a crucial role in the formation
      of unilocular large LDs in white adipocytes. However, the mechanisms by which
      brown adipocytes store small and multilocular LDs remain unclear. An FSP27
      isoform, FSP27beta, was recently identified. We herein report that CideA and
      FSP27beta are mainly expressed in brown adipose tissue and that FSP27beta
      overexpression inhibits CideA-induced LD enlargements in a dose-dependent manner
      in COS cells. Furthermore, RNAi-mediated FSP27beta depletion resulted in enlarged
      LDs in HB2 adipocytes, which possess the characteristics of brown adipocytes.
      Brown adipocytes in FSP27-knock-out mice that express CideA, but not FSP27beta,
      had larger and fewer LDs. Moreover, we confirmed that FSP27beta and CideA form a
      complex in brown adipose tissue. Our results suggest that FSP27beta negatively
      regulates CideA-promoted enlargement of LD size in brown adipocytes. FSP27beta
      appears to be responsible for the formation of small and multilocular LDs in
      brown adipose tissue, a morphology facilitating free fatty acid transport to
      mitochondria adjacent to LDs for oxidation in brown adipocytes.

PMID- 28490631
TI  - A split-luciferase complementation, real-time reporting assay enables monitoring
      of the disease-associated transmembrane protein TREM2 in live cells.
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) is a single
      transmembrane molecule uniquely expressed in microglia. TREM2 mutations are
      genetically linked to Nasu-Hakola disease and associated with multiple
      neurodegenerative disorders, including Alzheimer's disease. TREM2 may regulate
      microglial inflammation and phagocytosis through coupling to the adaptor protein
      TYRO protein-tyrosine kinase-binding protein (TYROBP). However, there is no
      functional system for monitoring this protein-protein interaction. We developed a
      luciferase-based modality for real-time monitoring of TREM2-TYROBP coupling in
      live cells that utilizes split-luciferase complementation technology based on
      TREM2 and TYROBP fusion to the C- or N-terminal portion of the Renilla luciferase
      gene. Transient transfection of human embryonic kidney 293 cells with this
      reporter vector increased luciferase activity upon stimulation with an anti-TREM2
      antibody, which induces their homodimerization. This was confirmed by ELISA-based
      analysis of the TREM2-TYROBP interaction. Antibody-mediated TREM2 stimulation
      enhanced spleen tyrosine kinase (SYK) activity and uptake of Staphylococcus
      aureus in microglial cell line BV-2 in a kinase-dependent manner. Interestingly,
      the TREM2 T66M mutation significantly enhanced luciferase activity without
      stimulation, indicating constitutive coupling to TYROBP. Finally, flow cytometry
      analyses indicated significantly lower surface expression of T66M TREM2 variant
      than wild type or other TREM2 variants. These results demonstrate that our TREM2
      reporter vector is a novel tool for monitoring the TREM2-TYROBP interaction in
      real time.

PMID- 28490633
TI  - Single-particle electron microscopy structure of UDP-glucose:glycoprotein
      glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
AB  - The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality
      control of glycoproteins in the endoplasmic reticulum by attaching glucose to N
      linked glycan of misfolded proteins. As a sensor, UGGT ensures that misfolded
      proteins are recognized by the lectin chaperones and do not leave the secretory
      pathway. The structure of UGGT and the mechanism of its selectivity for misfolded
      proteins have been unknown for 25 years. Here, we used negative-stain electron
      microscopy and small-angle X-ray scattering to determine the structure of UGGT
      from Drosophila melanogaster at 18-A resolution. Three-dimensional
      reconstructions revealed a cage-like structure with a large central cavity.
      Particle classification revealed flexibility that precluded determination of a
      high-resolution structure. Introduction of biotinylation sites into a fungal UGGT
      expressed in Escherichia coli allowed identification of the catalytic and first
      thioredoxin-like domains. We also used hydrogen-deuterium exchange mass
      spectrometry to map the binding site of an accessory protein, Sep15, to the first
      thioredoxin-like domain. The UGGT structural features identified suggest that the
      central cavity contains the catalytic site and is lined with hydrophobic
      surfaces. This enhances the binding of misfolded substrates with exposed
      hydrophobic residues and excludes folded proteins with hydrophilic surfaces. In
      conclusion, we have determined the UGGT structure, which enabled us to develop a
      plausible functional model of the mechanism for UGGT's selectivity for misfolded
      glycoproteins.

PMID- 28490634
TI  - Inflammatory cytokines down-regulate the barrier-protective prostasin-matriptase
      proteolytic cascade early in experimental colitis.
AB  - Compromised gastrointestinal barrier function is strongly associated with the
      progressive and destructive pathologies of the two main forms of irritable bowel
      disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD). Matriptase is a
      membrane-anchored serine protease encoded by suppression of tumorigenicity-14
      (ST14) gene, which is critical for epithelial barrier development and
      homeostasis. Matriptase barrier-protective activity is linked with the
      glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, which is a
      co-factor for matriptase zymogen activation. Here we show that mRNA and protein
      expression of both matriptase and prostasin are rapidly down-regulated in the
      initiating inflammatory phases of dextran sulfate sodium (DSS)-induced
      experimental colitis in mice, and, significantly, the loss of these proteases
      precedes the appearance of clinical symptoms, suggesting their loss may
      contribute to disease susceptibility. We used heterozygous St14 hypomorphic mice
      expressing a promoter-linked beta-gal reporter to show that inflammatory colitis
      suppresses the activity of the St14 gene promoter. Studies in colonic T84 cell
      monolayers revealed that barrier disruption by the colitis-associated Th2-type
      cytokines, IL-4 and IL-13, down-regulates matriptase as well as prostasin through
      phosphorylation of the transcriptional regulator STAT6 and that inhibition of
      STAT6 with suberoylanilide hydroxamic acid (SAHA) restores protease expression
      and reverses cytokine-induced barrier dysfunction. Both matriptase and prostasin
      are significantly down-regulated in colonic tissues from human subjects with
      active ulcerative colitis or Crohn's disease, implicating the loss of this
      barrier-protective protease pathway in the pathogenesis of irritable bowel
      disease.

PMID- 28490635
TI  - The FOXO transcription factor controls insect growth and development by
      regulating juvenile hormone degradation in the silkworm, Bombyx mori.
AB  - Forkhead box O (FOXO) functions as the terminal transcription factor of the
      insulin signaling pathway and regulates multiple physiological processes in many
      organisms, including lifespan in insects. However, how FOXO interacts with
      hormone signaling to modulate insect growth and development is largely unknown.
      Here, using the transgene-based CRISPR/Cas9 system, we generated and
      characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its
      physiological functions during development of this lepidopteran insect. The
      BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and
      showed precocious metamorphosis, pupating at the end of the fourth instar
      (trimolter) rather than at the end of the fifth instar as in the wild-type (WT)
      animals. However, different from previous reports on precocious metamorphosis
      caused by juvenile hormone (JH) deficiency in silkworm mutants, the total
      developmental time of the larval period in the FOXO-M was comparable with that of
      the WT. Exogenous application of 20-hydroxyecdysone (20E) or of the JH analog
      rescued the trimolter phenotype. RNA-seq and gene expression analyses indicated
      that genes involved in JH degradation but not in JH biosynthesis were up
      regulated in the FOXO-M compared with the WT animals. Moreover, we identified
      several FOXO-binding sites in the promoter of genes coding for JH-degradation
      enzymes. These results suggest that FOXO regulates JH degradation rather than its
      biosynthesis, which further modulates hormone homeostasis to control growth and
      development in B. mori In conclusion, we have uncovered a pivotal role for FOXO
      in regulating JH signaling to control insect development.

PMID- 28490636
TI  - The Cox1 C-terminal domain is a central regulator of cytochrome c oxidase
      biogenesis in yeast mitochondria.
AB  - Cytochrome c oxidase (CcO) is the last electron acceptor in the respiratory
      chain. The CcO core is formed by mitochondrial DNA-encoded Cox1, Cox2, and Cox3
      subunits. Cox1 synthesis is highly regulated; for example, if CcO assembly is
      blocked, Cox1 synthesis decreases. Mss51 activates translation of COX1 mRNA and
      interacts with Cox1 protein in high-molecular-weight complexes (COA complexes) to
      form the Cox1 intermediary assembly module. Thus, Mss51 coordinates both Cox1
      synthesis and assembly. We previously reported that the last 15 residues of the
      Cox1 C terminus regulate Cox1 synthesis by modulating an interaction of Mss51
      with Cox14, another component of the COA complexes. Here, using site-directed
      mutagenesis of the mitochondrial COX1 gene from Saccharomyces cerevisiae, we
      demonstrate that mutations P521A/P522A and V524E disrupt the regulatory role of
      the Cox1 C terminus. These mutations, as well as C terminus deletion
      (Cox1DeltaC15), reduced binding of Mss51 and Cox14 to COA complexes. Mss51 was
      enriched in a translationally active form that maintains full Cox1 synthesis even
      if CcO assembly is blocked in these mutants. Moreover, Cox1DeltaC15, but not Cox1
      P521A/P522A and Cox1-V524E, promoted formation of aberrant supercomplexes in CcO
      assembly mutants lacking Cox2 or Cox4 subunits. The aberrant supercomplex
      formation depended on the presence of cytochrome b and Cox3, supporting the idea
      that supercomplex assembly factors associate with Cox3 and demonstrating that
      supercomplexes can be formed even if CcO is inactive and not fully assembled. Our
      results indicate that the Cox1 C-terminal end is a key regulator of CcO
      biogenesis and that it is important for supercomplex formation/stability.

PMID- 28490637
TI  - Does Semantic Congruency Accelerate Episodic Encoding, or Increase Semantic
      Elaboration?

PMID- 28490638
TI  - Immunomodulation via Toll-like Receptor 9: An Adjunct Therapy Strategy against
      Alzheimer's Disease?

PMID- 28490640
TI  - Transcribing the connectome: roles for transcription factors and chromatin
      regulators in activity-dependent synapse development.
AB  - The wiring of synaptic connections in the developing mammalian brain is shaped by
      both intrinsic and extrinsic signals. One point where these regulatory pathways
      converge is via the sensory experience-dependent regulation of new gene
      transcription. Recent studies have elucidated a number of molecular mechanisms
      that allow nuclear transcription factors and chromatin regulatory proteins to
      encode aspects of specificity in experience-dependent synapse development. Here
      we review the evidence for the transcriptional mechanisms that sculpt activity
      dependent aspects of synaptic connectivity during postnatal development and
      discuss how disruption of these processes is associated with aberrant brain
      development in autism and intellectual disability.

PMID- 28490641
TI  - Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal
      chemosensory neurons to ethanol and its flavor components.
AB  - Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent
      rats and humans. We asked whether these behavioral changes may be mediated in
      part by changes in responsiveness of the peripheral taste and oral trigeminal
      systems. We exposed the experimental rats to ethanol in utero by administering
      ethanol to dams through a liquid diet; we exposed the control rats to an
      isocaloric and isonutritive liquid diet. To assess taste responsiveness, we
      recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to
      lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess
      trigeminal responsiveness, we measured changes in calcium levels of isolated
      trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin,
      mustard oil, and KCl. Compared with adolescent control rats, the adolescent
      experimental rats exhibited diminished CT nerve responses to ethanol, quinine,
      and sucrose and GL nerve responses to quinine and sucrose. The reductions in
      taste responsiveness persisted into adulthood for quinine but not for any of the
      other stimuli. Adolescent experimental rats also exhibited reduced TG neuron
      responses to ethanol, capsaicin, and mustard oil. The lack of change in
      responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates
      that FAE altered only a subset of the response pathways within each chemosensory
      system. We propose that FAE reprograms development of the peripheral taste and
      trigeminal systems in ways that reduce their responsiveness to ethanol and
      surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral
      burning) flavor attributes.NEW & NOTEWORTHY Pregnant mothers are advised to avoid
      alcohol. This is because even small amounts of alcohol can alter fetal brain
      development and increase the risk of adolescent alcohol abuse. We asked how fetal
      alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring
      responsiveness of taste nerves and trigeminal chemosensory neurons. We found that
      FAE substantially reduced taste and trigeminal responsiveness to ethanol and its
      flavor components.

PMID- 28490642
TI  - Split-arm swinging: the effect of arm swinging manipulation on interlimb
      coordination during walking.
AB  - Human locomotion is defined by bilateral coordination of gait (BCG) and shared
      features with the fore-hindlimb coordination of quadrupeds. The objective of the
      present study is to explore the influence of arm swinging (AS) on BCG. Sixteen
      young, healthy individuals (eight women; eight right motor-dominant, eight left
      motor dominant) participated. Participants performed 10 walking trials (2 min).
      In each of the trials AS was unilaterally manipulated (e.g., arm restriction,
      weight on the wrist), bilaterally manipulated, or not manipulated. The order of
      trials was random. Walking trials were performed on a treadmill. Gait kinematics
      were recorded by a motion capture system. Using feedback-controlled belt speed
      allowed the participants to walk at a self-determined gait speed. Effects of the
      manipulations were assessed by AS amplitudes and the phase coordination index
      (PCI), which quantifies the left-right anti-phased stepping pattern. Most of the
      AS manipulations caused an increase in PCI values (i.e., reduced lower limb
      coordination). Unilateral AS manipulation had a reciprocal effect on the AS
      amplitude of the other arm such that, for example, over-swinging of the right arm
      led to a decrease in the AS amplitude of the left arm. Side of motor dominance
      was not found to have a significant impact on PCI and AS amplitude. The present
      findings suggest that lower limb BCG is markedly influenced by the rhythmic AS
      during walking. It may thus be important for gait rehabilitation programs
      targeting BCG to take AS into account.NEW & NOTEWORTHY Control mechanisms for
      four-limb coordination in human locomotion are not fully known. To study the
      influence of arm swinging (AS) on bilateral coordination of the lower limbs
      during walking, we introduced a split-AS paradigm in young, healthy adults. AS
      manipulations caused deterioration in the anti-phased stepping pattern and
      impacted the AS amplitudes for the contralateral arm, suggesting that lower limb
      coordination is markedly influenced by the rhythmic AS during walking.

PMID- 28490643
TI  - Predicting the response of striatal spiny neurons to sinusoidal input.
AB  - Spike-timing effects of small-amplitude sinusoidal currents were measured in
      mouse striatal spiny neurons firing repetitively. Spike-timing reliability varied
      with the stimulus frequency. For frequencies near the cell's firing rate, the
      cells altered firing rate to match the stimulus and became phase locked to it.
      The stimulus phase of firing during lock depended on the stimulus frequency
      relative to the cell's unperturbed firing rate. Interspike intervals during
      sinusoidal stimulation were predicted using an iterative map constructed from the
      cells' phase-resetting curve. Variability of interspike intervals was reduced by
      stimulation at all frequencies higher than about half the cell's unperturbed
      rate, and interspike intervals were accurately predicted by the map. Long
      sequences of spike times were predicted by iterating on the map. The accuracy of
      that prediction varied with frequency. Spike time predictability was highest near
      and during phase lock. The map predicted the phase of firing on the input and its
      dependence on stimulus frequency. Prediction errors, when they occurred, were of
      two kinds: unpredicted variation in interspike interval from intrinsic cell noise
      and accumulation of prediction errors from previous interspike intervals. Each
      type of prediction error arose from a different mechanism, and their impact was
      also predicted from the phase model. When two oscillatory input currents were
      presented simultaneously, striatal neurons responded selectively to only one of
      them, the one closest in frequency to the cell's unperturbed firing rate. Their
      spike times encoded the frequency and phase of that single oscillatory input.NEW
      & NOTEWORTHY During repetitive firing, the timing of action potentials is
      determined by the interaction between the input and voltage-sensitive currents
      throughout the interspike interval. This interaction is encapsulated in the
      neuron's phase-resetting curve. The phase-resetting curve predicted spike timing
      to small sinusoidal currents over a wide range of stimulus frequencies. Firing
      patterns were most sensitive to oscillatory components near the cell's own firing
      rate, even in the presence of noise and other inputs.

PMID- 28490645
TI  - Evidence of adaptations of locomotor neural drive in response to enhanced
      intermuscular connectivity between the triceps surae muscles of the rat.
AB  - The aims of this study were to investigate changes 1) in the coordination of
      activation of the triceps surae muscle group, and 2) in muscle belly length of
      soleus (SO) and lateral gastrocnemius (LG) during locomotion (trotting) in
      response to increased stiffness of intermuscular connective tissues in the rat.
      We measured muscle activation and muscle belly lengths, as well as hindlimb
      kinematics, before and after an artificial enhancement of the connectivity
      between SO and LG muscles obtained by implanting a tissue-integrating surgical
      mesh at the muscles' interface. We found that SO muscle activation decreased to
      62%, while activation of LG and medial gastrocnemius muscles increased to 134 and
      125%, respectively, compared with the levels measured preintervention. Although
      secondary additional or amplified activation bursts were observed with enhanced
      connectivity, the primary pattern of activation over the stride and the burst
      duration were not affected by the intervention. Similar muscle length changes
      after manipulation were observed, suggesting that length feedback from spindle
      receptors within SO and LG was not affected by the connectivity enhancement. We
      conclude that peripheral mechanical constraints given by morphological
      (re)organization of connective tissues linking synergists are taken into account
      by the central nervous system. The observed shift in activity toward the
      gastrocnemius muscles after the intervention suggests that these larger muscles
      are preferentially recruited when the soleus has a similar mechanical
      disadvantage in that it produces an unwanted flexion moment around the knee.NEW &
      NOTEWORTHY Connective tissue linkages between muscle-tendon units may act as an
      additional mechanical constraint on the musculoskeletal system, thereby reducing
      the spectrum of solutions for performing a motor task. We found that
      intermuscular coordination changes following intermuscular connectivity
      enhancement. Besides showing that the extent of such connectivity is taken into
      account by the central nervous system, our results suggest that recruitment of
      triceps surae muscles is governed by the moments produced at the ankle-knee
      joints.

PMID- 28490644
TI  - Background noise exerts diverse effects on the cortical encoding of foreground
      sounds.
AB  - In natural listening conditions, many sounds must be detected and identified in
      the context of competing sound sources, which function as background noise.
      Traditionally, noise is thought to degrade the cortical representation of sounds
      by suppressing responses and increasing response variability. However, recent
      studies of neural network models and brain slices have shown that background
      synaptic noise can improve the detection of signals. Because acoustic noise
      affects the synaptic background activity of cortical networks, it may improve the
      cortical responses to signals. We used spike train decoding techniques to
      determine the functional effects of a continuous white noise background on the
      responses of clusters of neurons in auditory cortex to foreground signals,
      specifically frequency-modulated sweeps (FMs) of different velocities,
      directions, and amplitudes. Whereas the addition of noise progressively
      suppressed the FM responses of some cortical sites in the core fields with
      decreasing signal-to-noise ratios (SNRs), the stimulus representation remained
      robust or was even significantly enhanced at specific SNRs in many others. Even
      though the background noise level was typically not explicitly encoded in
      cortical responses, significant information about noise context could be decoded
      from cortical responses on the basis of how the neural representation of the
      foreground sweeps was affected. These findings demonstrate significant diversity
      in signal in noise processing even within the core auditory fields that could
      support noise-robust hearing across a wide range of listening conditions.NEW &
      NOTEWORTHY The ability to detect and discriminate sounds in background noise is
      critical for our ability to communicate. The neural basis of robust perceptual
      performance in noise is not well understood. We identified neuronal populations
      in core auditory cortex of squirrel monkeys that differ in how they process
      foreground signals in background noise and that may contribute to robust signal
      representation and discrimination in acoustic environments with prominent
      background noise.

PMID- 28490647
TI  - Placebo and nocebo responses in restless legs syndrome: A systematic review and
      meta-analysis.
AB  - OBJECTIVE: To estimate the placebo and nocebo responses in restless legs syndrome
      (RLS) and explore their determinants. METHODS: Databases were searched up to
      October 2015. Randomized, double-blind, placebo-controlled trials of patients
      with RLS were included if quantitative data were extractable in the placebo arm.
      Placebo response was defined as the within-group change from baseline, using any
      scale measuring RLS severity or disability. Nocebo response was defined as the
      proportion of patients experiencing adverse events in the placebo arm. Random
      effects meta-analysis was used to pool data. Statistical heterogeneity was
      assessed with I2 statistic. Several predetermined subgroup and sensitivity
      analysis were performed. PROSPERO registration number is CRD42015027992. RESULTS:
      We included 85 randomized controlled trials (5,046 participants). Pooled placebo
      response effect size was -1.41 (95% confidence interval [CI] -1.56 to -1.25, 64
      trials, I2 = 88.1%), corresponding to -6.58 points in the International RLS Study
      Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%-50.29%, 72
      trials; I2 = 89.8%). The placebo and nocebo responses were greater in trials with
      longer duration, evaluating pharmacologic interventions and idiopathic RLS, and
      in industry-funded and unpublished studies. The placebo response was considerably
      smaller in objective as compared to subjective outcomes. In addition, the nocebo
      response increases proportionally with the placebo response, and has the same
      predictors. CONCLUSIONS: The magnitude of the placebo response in RLS is above
      the threshold of minimal clinical important difference, and the frequency of
      adverse events is also considerable. These results are relevant to inform the
      design and interpretation of future clinical trials.

PMID- 28490646
TI  - A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or
      rod depolarizing bipolar cell function.
AB  - GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal
      depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and
      underlie the human condition autosomal recessive complete congenital stationary
      night blindness. Mouse mutants for Grm6 are important models for this condition.
      Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen
      of mice maintained at The Jackson Laboratory. The Grm6nob8 mouse has a reduced
      amplitude b-wave component of the ERG, which reflects light-evoked DBC activity.
      Sequencing identified a missense mutation that converts a highly conserved
      methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent
      with prior studies of Grm6 mutant mice, the laminar size and structure in the
      Grm6nob8 retina were comparable to control. The Grm6nob8 phenotype is
      distinguished from other Grm6 mutants that carry a null allele by a reduced but
      not absent ERG b-wave, decreased but present expression of mGluR6 at DBC
      dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a
      reduced but not absent b-wave, there were a subset of retinal ganglion cells
      whose responses to light onset have times to peak within the range of those in
      control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is
      trafficked less than control. However, the mGluR6 that is localized to the DBC
      dendritic tips is able to initiate DBC signal transduction. The Grm6nob8 mouse
      extends the Grm6 allelic series and will be useful for elucidating the role of
      mGluR6 in DBC signal transduction and in human disease.NEW & NOTEWORTHY This
      article describes a mouse model of the human disease complete congenital
      stationary night blindness in which the mutation reduces but does not eliminate
      GRM6 expression and bipolar cell function, a distinct phenotype from that seen in
      other Grm6 mouse models.

PMID- 28490648
TI  - Randomized trial of preladenant, given as monotherapy, in patients with early
      Parkinson disease.
AB  - OBJECTIVE: To evaluate the adenosine 2a receptor antagonist preladenant as a
      nondopaminergic drug for the treatment of Parkinson disease (PD) when given as
      monotherapy. METHODS: This was a randomized, 26-week, placebo- and active
      controlled, parallel-group, multicenter, double-blind trial conducted in adults
      diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine
      agonists. Patients with a Unified Parkinson's Disease Rating Scale (UPDRS) part 3
      (motor function) score >=10 and Hoehn & Yahr score <=3 were randomized 1:1:1:1:1
      to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once
      daily, or placebo. The primary endpoint was the change from baseline at week 26
      in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).
      RESULTS: The number of patients treated was 1,007. Neither preladenant nor
      rasagiline was superior to placebo after 26 weeks. The differences vs placebo
      (95% confidence interval) in UPDRS2+3 scores (with a negative difference
      indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30),
      preladenant 5 mg = 1.30 (-0.41, 2.94), preladenant 10 mg = 0.40 (-1.29, 2.11),
      and rasagiline 1 mg = 0.30 (-1.35, 2.03). Post hoc analyses did not identify a
      single causal factor that could explain the finding of a failed trial.
      Preladenant was generally well-tolerated with few patients discontinuing due to
      adverse events (preladenant 7%, rasagiline 3%, placebo 4%). CONCLUSIONS: No
      evidence supporting the efficacy of preladenant as monotherapy was observed in
      this phase 3 trial. The lack of efficacy of the active control rasagiline makes
      it difficult to interpret the results. CLINICAL TRIAL REGISTRATION:
      Clinicaltrials.gov: NCT01155479. CLASSIFICATION OF EVIDENCE: This study provides
      Class I evidence that for patients with early PD, preladenant is not effective as
      monotherapy at the doses studied (2, 5, 10 mg).

PMID- 28490649
TI  - Pathologic confirmation of retinal ganglion cell loss in multiple system atrophy.

PMID- 28490650
TI  - The American Academy of Neurology affirms the revival of cooling for the revived.

PMID- 28490651
TI  - Effects of MCI subtype and reversion on progression to dementia in a community
      sample.
AB  - OBJECTIVE: We sought to understand the trajectory of mild cognitive impairment
      (MCI) better by examining longitudinally different MCI subtypes and progression
      to dementia and reversion to normal cognition in a community sample. METHODS: We
      evaluated the stability of MCI subtypes and risk of dementia over 4 biennial
      assessments as part of an ongoing prospective cohort study, the Sydney Memory and
      Ageing Study. RESULTS: While prevalence of MCI and different MCI subtypes remains
      relatively stable across all assessments, reversion from MCI and transitions
      between different MCI subtypes were common. Up to 46.5% of participants
      classified with MCI at baseline reverted at some point during follow-up. The
      majority (83.8%) of participants with incident dementia were diagnosed with MCI 2
      years prior to their dementia diagnosis. Both reverters and participants with
      stable MCI were at an increased risk of progression to dementia compared to those
      without MCI at baseline (HR 6.4, p = 0.02, and HR 24.7, p < 0.001, respectively);
      however, the risk of dementia in participants with MCI who did not revert was
      higher than in reverters (HR 2.5, p = 0.01). This effect was specific to amnestic
      subtypes (MCI reverters vs nonreverters: amnestic MCI HR 3.3, p = 0.006;
      nonamnestic MCI: HR 1.3, p = 0.67). CONCLUSION: Our findings indicate that the
      relevance of reversion for progression risk depends on the MCI subtype. Subtype
      specificity and longitudinal characterization are required for the reliable
      identification of individuals at high risk of developing dementia.

PMID- 28490652
TI  - Restless legs syndrome: Losing sleep over the placebo response.

PMID- 28490653
TI  - Prospective association between beta2-microglobulin levels and ischemic stroke
      risk among women.
AB  - OBJECTIVE: To determine whether elevated beta2-microglobulin (B2M) levels were
      associated with an increased risk of incident ischemic stroke events among women.
      METHODS: We performed a nested case-control study among women enrolled in the
      Nurses' Health Study who provided blood samples between 1989 and 1990 and were
      free of prior stroke and cancer. We measured B2M levels in 473 ischemic strokes
      cases confirmed by medical record review and in 473 controls matched 1:1 to the
      cases on age, race, date of blood collection, menopausal status, postmenopausal
      hormone use, and smoking status. We analyzed the association between B2M and
      ischemic stroke using multivariable conditional logistic regression to adjust for
      traditional stroke risk factors. RESULTS: Median levels of B2M were higher among
      cases (1.86 mg/L) than controls (1.80 mg/L, p = 0.009, Wilcoxon rank-sum test).
      Women in the highest B2M quartile had a multivariable-adjusted increased risk of
      ischemic stroke compared to those in the lowest quartile (odds ratio [OR] 1.56,
      95% confidence interval [CI] 1.02-2.39). Results were similar when restricted to
      those without evidence of chronic kidney disease (estimated glomerular filtration
      rate >=60 mL.min-1.1.73 m-2) (OR 1.49, 95% CI 1.08-2.06). In an exploratory
      analysis, the association between B2M and thrombotic stroke was similar to the
      overall ischemic stroke results, but no association was observed for embolic
      stroke risk. CONCLUSION: High levels of B2M were associated with an increased
      risk of ischemic stroke among women.

PMID- 28490654
TI  - Early skin denervation in hereditary and iatrogenic transthyretin amyloid
      neuropathy.
AB  - OBJECTIVE: To elucidate early skin denervation in hereditary transthyretin (TTR)
      amyloidosis and iatrogenic TTR amyloidosis. METHODS: We investigated
      intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients
      with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients
      with iatrogenic TTR amyloidosis, and 23 healthy volunteers. RESULTS: IENFD values
      were reduced in patients with the V30M mutation (1.9 +/- 2.1 per 1 mm), patients
      with non-V30M mutations (5.8 +/- 3.2 per 1 mm), and patients with iatrogenic TTR
      amyloidosis (3.5 +/- 1.8 per 1 mm) compared with healthy volunteers (11.8 +/- 3.2
      per 1 mm) (p < 0.01). Skin denervation also occurred, even in presymptomatic V30M
      mutation carriers (5.0 +/- 2.2 per 1 mm). The IENFD was correlated with disease
      duration (rho = -0.533, p = 0.002) and various peripheral neuropathy parameters
      such as sensory impairment in the Kumamoto clinical score (rho = -0.575, p =
      0.001), heat-pain detection threshold (rho = -0.704, p < 0.001), and sural
      sensory nerve action potential (rho = 0.481, p = 0.005). TTR amyloid deposits
      frequently occurred in connective tissues and vessels of the dermal reticular
      layer in patients with hereditary TTR amyloidosis and those with iatrogenic TTR
      amyloidosis. CONCLUSIONS: Patients with hereditary TTR amyloidosis and those with
      iatrogenic TTR amyloidosis may show early skin denervation even in the
      presymptomatic stage. IENFD may thus be useful for early diagnosis and may serve
      as a biomarker in clinical trials for hereditary and iatrogenic TTR amyloidosis.

PMID- 28490655
TI  - Practice guideline summary: Reducing brain injury following cardiopulmonary
      resuscitation: Report of the Guideline Development, Dissemination, and
      Implementation Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To assess the evidence and make evidence-based recommendations for
      acute interventions to reduce brain injury in adult patients who are comatose
      after successful cardiopulmonary resuscitation. METHODS: Published literature
      from 1966 to August 29, 2016, was reviewed with evidence-based classification of
      relevant articles. RESULTS AND RECOMMENDATIONS: For patients who are comatose in
      whom the initial cardiac rhythm is either pulseless ventricular tachycardia (VT)
      or ventricular fibrillation (VF) after out-of-hospital cardiac arrest (OHCA),
      therapeutic hypothermia (TH; 32-34 degrees C for 24 hours) is highly likely to be
      effective in improving functional neurologic outcome and survival compared with
      non-TH and should be offered (Level A). For patients who are comatose in whom the
      initial cardiac rhythm is either VT/VF or asystole/pulseless electrical activity
      (PEA) after OHCA, targeted temperature management (36 degrees C for 24 hours,
      followed by 8 hours of rewarming to 37 degrees C, and temperature maintenance
      below 37.5 degrees C until 72 hours) is likely as effective as TH and is an
      acceptable alternative (Level B). For patients who are comatose with an initial
      rhythm of PEA/asystole, TH possibly improves survival and functional neurologic
      outcome at discharge vs standard care and may be offered (Level C). Prehospital
      cooling as an adjunct to TH is highly likely to be ineffective in further
      improving neurologic outcome and survival and should not be offered (Level A).
      Other pharmacologic and nonpharmacologic strategies (applied with or without
      concomitant TH) are also reviewed.

PMID- 28490656
TI  - Role of habenula and amygdala dysfunction in Parkinson disease patients with
      punding.
AB  - OBJECTIVE: To assess whether a functional dysregulation of the habenula and
      amygdala, as modulators of the reward brain circuit, contributes to Parkinson
      disease (PD) punding. METHODS: Structural and resting-state functional MRI were
      obtained from 22 patients with PD punding, 30 patients with PD without any
      impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor
      impairment, and cognitive status, and 30 healthy controls. Resting-state
      functional connectivity of the habenula and amygdala bilaterally was assessed
      using a seed-based approach. Habenula and amygdala volumes and cortical thickness
      measures were obtained. RESULTS: Compared to both healthy controls and PD cases
      without any ICB (PD-no ICB), PD-punding patients showed higher functional
      connectivity of habenula and amygdala with thalamus and striatum bilaterally, and
      lower connectivity between bilateral habenula and left frontal and precentral
      cortices. In PD-punding relative to PD-no ICB patients, a lower functional
      connectivity between right amygdala and hippocampus was also observed. Habenula
      and amygdala volumes were not different among groups. PD-punding patients showed
      a cortical thinning of the left superior frontal and precentral gyri and right
      middle temporal gyrus and isthmus cingulate compared to healthy controls, and of
      the right inferior frontal gyrus compared to both controls and PD-no ICB
      patients. CONCLUSIONS: A breakdown of the connectivity among the crucial nodes of
      the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex)
      might be a contributory factor to punding in PD. This study provides potential
      instruments to detect and monitor punding in patients with PD.

PMID- 28490657
TI  - Targeting endogenous proteins for degradation through the affinity-directed
      protein missile system.
AB  - Targeted proteolysis of endogenous proteins is desirable as a research toolkit
      and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and
      often not feasible for many genes. Similarly, RNA interference approaches
      necessitate prolonged treatments, can lead to incomplete knockdowns and are often
      associated with off-target effects. Targeted proteolysis can overcome these
      limitations. In this report, we describe an affinity-directed protein missile
      (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate
      receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders
      that selectively bind and recruit endogenous target proteins to the CUL2-E3
      ligase complex for ubiquitination and proteasomal degradation. By using synthetic
      monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a
      camelid-derived VHH nanobody that selectively binds the human ASC protein, we
      demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and
      ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells
      impacts SHP2 biology. This study demonstrates for the first time that small
      polypeptide binders that selectively recognize endogenous target proteins can be
      exploited for AdPROM-mediated destruction of the target proteins.

PMID- 28490659
TI  - RUNX transcription factors at the interface of stem cells and cancer.
AB  - The RUNX1 transcription factor is a critical regulator of normal haematopoiesis
      and its functional disruption by point mutations, deletions or translocations is
      a major causative factor leading to leukaemia. In the majority of cases, genetic
      changes in RUNX1 are linked to loss of function classifying it broadly as a
      tumour suppressor. Despite this, several recent studies have reported the need
      for a certain level of active RUNX1 for the maintenance and propagation of acute
      myeloid leukaemia and acute lymphoblastic leukaemia cells, suggesting an
      oncosupportive role of RUNX1. Furthermore, in solid cancers, RUNX1 is
      overexpressed compared with normal tissue, and RUNX factors have recently been
      discovered to promote growth of skin, oral, breast and ovarian tumour cells,
      amongst others. RUNX factors have key roles in stem cell fate regulation during
      homeostasis and regeneration of many tissues. Cancer cells appear to have
      corrupted these stem cell-associated functions of RUNX factors to promote
      oncogenesis. Here, we discuss current knowledge on the role of RUNX genes in stem
      cells and as oncosupportive factors in haematological malignancies and epithelial
      cancers.

PMID- 28490660
TI  - Hiding in plain sight: immune evasion by the staphylococcal protein SdrE.
AB  - The human immune system is responsible for identification and destruction of
      invader cells, such as the bacterial pathogen Staphylococcus aureus In response,
      S. aureus brings to the fight a large number of virulence factors, including
      several that allow it to evade the host immune response. The staphylococcal
      surface protein SdrE was recently reported to bind to complement Factor H, an
      important regulator of complement activation. Factor H attaches to the surface of
      host cells to inhibit complement activation and amplification, preventing the
      destruction of the host cell. SdrE binding to Factor H allows S. aureus to mimic
      a host cell and reduces bacterial killing by granulocytes. In a new study
      published in Biochemical Journal, Zhang et al. describe crystal structures of
      SdrE and its complex with the C-terminal portion of Factor H. The structure of
      SdrE and its interaction with the Factor H peptide closely resemble a family of
      surface proteins that recognize extracellular matrix components such as
      fibrinogen. However, unbound SdrE forms a novel 'Closed' conformation with an
      occluded peptide-binding groove. These structures reveal a fascinating mechanism
      for immune evasion and provide a potential avenue for the development of novel
      antimicrobial agents to target SdrE.

PMID- 28490661
TI  - Surgery for subacromial impingement syndrome in relation to occupational
      exposures, lifestyle factors and diabetes mellitus: a nationwide nested case
      control study.
AB  - OBJECTIVES: To estimate the risk of surgery for subacromial impingement syndrome
      (SIS) in relation to occupational exposures, lifestyle factors and diabetes
      mellitus. METHODS: We conducted a case-control study nested in a register-based
      cohort study of the Danish working population. For each of 3000 first-time cases
      of surgery for SIS, two age-matched and sex-matched controls were drawn. Cases
      and controls received a questionnaire on job history and other factors. Job
      histories were combined with a psychosocial job exposure matrix (JEM) and the
      updated Shoulder JEM, which provided exposure intensities on measurement scales.
      Ten-year cumulative exposures to upper arm elevation >90 degrees , repetitive
      shoulder movements, forceful shoulder exertions and hand-arm vibrations (HAVs)
      were estimated. We used conditional logistic regression. RESULTS: There were 5396
      persons (60%) who answered the questionnaire. For occupational mechanical
      exposures, the adjusted OR (ORadj) ranged from 1.9 (95% CI 1.5 to 2.5 for HAVs)
      to 2.5 (95% CI 1.9 to 3.5 for force) among men and 1.7 (95% CI 1.2 to 2.5 for
      HAVs) to 2.0 (95% CI 1.3 to 2.9 for force) among women. No statistically
      significant associations were found for occupational psychosocial factors. Body
      mass index (BMI) and pack-years of smoking showed ORadj up to 2.0. Diabetes
      mellitus showed ORadj of 1.5 (95% CI 1.1 to 2.2) for men and 2.2 (95% CI 1.4 to
      3.4) for women. CONCLUSIONS: Our findings add to the evidence of an increased
      risk of surgery for SIS in relation to occupational cumulative mechanical
      exposures, even when an increased risk in relation to BMI, smoking and diabetes
      mellitus is taken into account.

PMID- 28490662
TI  - Occupational exposure to endotoxins and lung cancer risk: results of the ICARE
      Study.
AB  - OBJECTIVES: To investigate the role of occupational exposure to endotoxins in
      lung cancer in a French population-based case-control study (ICARE (Investigation
      of occupational and environmental causes of respiratory cancers)). METHODS:
      Detailed information was collected on the occupational history and smoking habits
      from 2926 patients with histologically confirmed lung cancer and 3555 matched
      controls. We evaluated each subject's endotoxin exposure after cross referencing
      International Standard Classification of Occupations (ISCO) codes (for job tasks)
      and Nomenclature d'Activites Francaises (NAF) codes (for activity sectors).
      Endotoxin exposure levels were attributed to each work environment based on
      literature reports. ORs and 95% CIs were estimated using unconditional logistic
      regression models and controlled for main confounding factors. RESULTS: An
      inverse association between exposure to endotoxins and lung cancer was found
      (OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and
      cumulative exposure, and the risk was decreased decades after exposure cessation
      (all statistically significant). Lung cancer risk was particularly reduced among
      workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in
      those weakly exposed (eg, in waste treatment). Statistically significant
      interactions were shown with smoking, and never/light smokers were more sensitive
      to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and
      OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest
      cumulative exposure, compared with those never exposed). Pronounced inverse
      associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI
      0.25 to 0.55 in the highly exposed). CONCLUSIONS: Our findings suggest that
      exposure to endotoxins, even at a low level, reduces the risk of lung cancer.

PMID- 28490663
TI  - Quantitative estimated exposure to vinyl chloride and risk of angiosarcoma of the
      liver and hepatocellular cancer in the US industry-wide vinyl chloride cohort:
      mortality update through 2013.
AB  - OBJECTIVE: To evaluate mortality risks of angiosarcoma of the liver (ASL),
      primary hepatocellular carcinoma (HCC) and other cancers among 9951 men employed
      between 1942 and 1972 at 35 US vinyl chloride (VC) or polyvinyl chloride plants
      followed for mortality through 31 December 2013. METHODS: SMR and time-dependent
      Cox proportional hazards analyses were used to evaluate mortality risks by
      cumulative VC exposure. RESULTS: Liver cancer mortality was elevated (SMR=2.87,
      95% CI 2.40 to 3.40), and ASL and HCC were strongly associated with cumulative VC
      exposure >=865 parts per million-years (ppm-years) (ASL: HR=36.3, 95% CI 13.1 to
      100.5; and HCC: HR=5.3, 95% CI 1.6 to 17.7 for >=2271 ppm-years). Excess deaths
      due to connective and soft tissue cancers (SMR=2.43, 95% CI 1.48 to 3.75),
      mesothelioma (SMR=2.29, 95% CI 1.18 to 4.00) and explosions (SMR=3.43, 95% CI
      1.25 to 7.47) were seen. Mortalities due to melanoma, brain cancer, lung cancer
      and non-Hodgkin's lymphoma were not increased or associated with VC exposure.
      CONCLUSION: The association between VC and ASL first reported in this cohort 44
      years ago persisted and was strongest among workers most highly exposed. VC
      exposure also was associated with HCC mortality, although it remains possible
      that misdiagnosis of early ASLs influenced findings.

PMID- 28490664
TI  - Inhibiting the oncogenic translation program is an effective therapeutic strategy
      in multiple myeloma.
AB  - Multiple myeloma (MM) is a frequently incurable hematological cancer in which
      overactivity of MYC plays a central role, notably through up-regulation of
      ribosome biogenesis and translation. To better understand the oncogenic program
      driven by MYC and investigate its potential as a therapeutic target, we screened
      a chemically diverse small-molecule library for anti-MM activity. The most potent
      hits identified were rocaglate scaffold inhibitors of translation initiation.
      Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven
      transcriptional program by CMLD010509, the most promising rocaglate. Proteome
      wide reversion correlated with selective depletion of short-lived proteins that
      are key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF, and MCL-1.
      The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic
      relevance of these findings in vivo and supports the feasibility of targeting the
      oncogenic MYC-driven translation program in MM with rocaglates.

PMID- 28490666
TI  - The path of least antibiotic resistance.
AB  - Antibiotic combination therapy alters Mycobacterium tuberculosis population
      dynamics in the human host.

PMID- 28490665
TI  - In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway
      in anti-PD-1 therapy.
AB  - Monoclonal antibodies (mAbs) targeting the immune checkpoint anti-programmed cell
      death protein 1 (aPD-1) have demonstrated impressive benefits for the treatment
      of some cancers; however, these drugs are not always effective, and we still have
      a limited understanding of the mechanisms that contribute to their efficacy or
      lack thereof. We used in vivo imaging to uncover the fate and activity of aPD-1
      mAbs in real time and at subcellular resolution in mice. We show that aPD-1 mAbs
      effectively bind PD-1+ tumor-infiltrating CD8+ T cells at early time points after
      administration. However, this engagement is transient, and aPD-1 mAbs are
      captured within minutes from the T cell surface by PD-1- tumor-associated
      macrophages. We further show that macrophage accrual of aPD-1 mAbs depends both
      on the drug's Fc domain glycan and on Fcgamma receptors (FcgammaRs) expressed by
      host myeloid cells and extend these findings to the human setting. Finally, we
      demonstrate that in vivo blockade of FcgammaRs before aPD-1 mAb administration
      substantially prolongs aPD-1 mAb binding to tumor-infiltrating CD8+ T cells and
      enhances immunotherapy-induced tumor regression in mice. These investigations
      yield insight into aPD-1 target engagement in vivo and identify specific
      Fc/FcgammaR interactions that can be modulated to improve checkpoint blockade
      therapy.

PMID- 28490667
TI  - Working memory: The real VIP.
AB  - Interneurons expressing VIP may play a causal role in working memory.

PMID- 28490668
TI  - "TrkA"cking why "no pain, no gain" is the rule for bone formation.
AB  - Peripheral sensory nerves expressing TrkA innervate long bones and stimulate bone
      formation through the Wnt/beta-catenin pathway when placed under stress.

PMID- 28490669
TI  - HIV-associated anaerobes ferment TB risk.
AB  - Short-chain fatty acids produced by anaerobic bacteria increase the risk of TB in
      HIV-infected, antiretroviral drug-treated people.

PMID- 28490670
TI  - Leukotriene B4 antagonism ameliorates experimental lymphedema.
AB  - Acquired lymphedema is a cancer sequela and a global health problem currently
      lacking pharmacologic therapy. We have previously demonstrated that ketoprofen,
      an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory
      properties, effectively reverses histopathology in experimental lymphedema. We
      show that the therapeutic benefit of ketoprofen is specifically attributable to
      its inhibition of the 5-lipoxygenase metabolite leukotriene B4 (LTB4). LTB4
      antagonism reversed edema, improved lymphatic function, and restored lymphatic
      architecture in the murine tail model of lymphedema. In vitro, LTB4 was
      functionally bimodal: Lower LTB4 concentrations promoted human lymphatic
      endothelial cell sprouting and growth, but higher concentrations inhibited
      lymphangiogenesis and induced apoptosis. During lymphedema progression, lymphatic
      fluid LTB4 concentrations rose from initial prolymphangiogenic concentrations
      into an antilymphangiogenic range. LTB4 biosynthesis was similarly elevated in
      lymphedema patients. Low concentrations of LTB4 stimulated, whereas high
      concentrations of LTB4 inhibited, vascular endothelial growth factor receptor 3
      and Notch pathways in cultured human lymphatic endothelial cells. Lymphatic
      specific Notch1-/- mice were refractory to the beneficial effects of LTB4
      antagonism, suggesting that LTB4 suppression of Notch signaling is an important
      mechanism in disease maintenance. In summary, we found that LTB4 was harmful to
      lymphatic repair at the concentrations observed in established disease. Our
      findings suggest that LTB4 is a promising drug target for the treatment of
      acquired lymphedema.

PMID- 28490671
TI  - Matched preclinical designs for improved translatability.
AB  - A more stratified preclinical design strategy will increase the statistical power
      and reproducibility of animal studies and their translatability.

PMID- 28490673
TI  - Development and Evaluation of the National Cancer Institute's Dietary Screener
      Questionnaire Scoring Algorithms.
AB  - Background: Methods for improving the utility of short dietary assessment
      instruments are needed.Objective: We sought to describe the development of the
      NHANES Dietary Screener Questionnaire (DSQ) and its scoring algorithms and
      performance.Methods: The 19-item DSQ assesses intakes of fruits and vegetables,
      whole grains, added sugars, dairy, fiber, and calcium. Two nonconsecutive 24-h
      dietary recalls and the DSQ were administered in NHANES 2009-2010 to respondents
      aged 2-69 y (n = 7588). The DSQ frequency responses, coupled with sex- and age
      specific portion size information, were regressed on intake from 24-h recalls by
      using the National Cancer Institute usual intake method to obtain scoring
      algorithms to estimate mean and prevalences of reaching 2 a priori threshold
      levels. The resulting scoring algorithms were applied to the DSQ and compared
      with intakes estimated with the 24-h recall data only. The stability of the
      derived scoring algorithms was evaluated in repeated sampling. Finally, scoring
      algorithms were applied to screener data, and these estimates were compared with
      those from multiple 24-h recalls in 3 external studies.Results: The DSQ and its
      scoring algorithms produced estimates of mean intake and prevalence that agreed
      closely with those from multiple 24-h recalls. The scoring algorithms were stable
      in repeated sampling. Differences in the means were <2%; differences in
      prevalence were <16%. In other studies, agreement between screener and 24-h
      recall estimates in fruit and vegetable intake varied. For example, among men in
      2 studies, estimates from the screener were significantly lower than the 24-h
      recall estimates (3.2 compared with 3.8 and 3.2 compared with 4.1). In the third
      study, agreement between the screener and 24-h recall estimates were close among
      both men (3.2 compared with 3.1) and women (2.6 compared with 2.5).Conclusions:
      This approach to developing scoring algorithms is an advance in the use of
      screeners. However, because these algorithms may not be generalizable to all
      studies, a pilot study in the proposed study population is advisable. Although
      more precise instruments such as 24-h dietary recalls are recommended in most
      research, the NHANES DSQ provides a less burdensome alternative when time and
      resources are constrained and interest is in a limited set of dietary factors.

PMID- 28490674
TI  - Physical Form of Dietary Fat Alters Postprandial Substrate Utilization and
      Glycemic Response in Healthy Chinese Men.
AB  - Background: Dietary fats elicit various physiological responses, with the
      physical form of fat reported to alter fat digestion and absorption.Objectives:
      The primary aims were to compare the effects of dietary fat in 2 physical forms
      (liquid and oleogel) and 2 degrees of saturation (saturated and polyunsaturated)
      on postprandial energy expenditure (EE) and substrate oxidation, glycemia, and
      appetite.Methods: The study was a randomized, controlled crossover trial. Sixteen
      normal-weight, healthy Chinese men completed the study [mean +/- SD age: 28 +/- 6
      y; body mass index (in kg/m2): 22.9 +/- 3.1]. After an overnight fast,
      participants had their body weight measured and entered an indirect whole-room
      calorimeter (WRC). After baseline measurements, participants consumed orange
      juice and rice porridge alone (control), with 22.25 g coconut oil or sunflower
      oil or with 25 g coconut oleogel or sunflower oleogel in random order with a 5-d
      washout period between treatments. EE, substrate oxidation, capillary blood
      glucose, and appetite were measured over 195 min in a WRC. Participants completed
      a meal challenge to assess appetite. Test meals effects were compared by using
      repeated-measures ANOVA.Results: Fat saturation did not affect all study outcomes
      significantly. When data were pooled based on the physical form of dietary fat,
      EE did not differ. However, significantly higher carbohydrate oxidation (P =
      0.03) and a trend of lower fat oxidation (P = 0.07) were found after the liquid
      oil than after the oleogel or control treatments. Postprandial capillary glucose
      was also significantly lower after the liquid oil than after the oleogel or
      control treatments (P < 0.001). Appetite was not affected by the physical form
      and the saturation of dietary fats.Conclusions: The saturation of dietary fat did
      not affect postprandial glucose, EE, substrate oxidation, or appetite. However,
      oleogel prevented the glycemic-lowering and fat-oxidation effects induced by
      liquid oil in Chinese men. Future work on oleogel should focus on cardiometabolic
      risk factors. This study was registered at clinicaltrials.gov as NCT02702726.

PMID- 28490672
TI  - Phenome-wide scanning identifies multiple diseases and disease severity
      phenotypes associated with HLA variants.
AB  - Although many phenotypes have been associated with variants in human leukocyte
      antigen (HLA) genes, the full phenotypic impact of HLA variants across all
      diseases is unknown. We imputed HLA genomic variation from two populations of
      28,839 and 8431 European ancestry individuals and tested association of HLA
      variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA
      allele phenotype associations were significant in both discovery and replication
      cohorts, the strongest being HLA-DQB1*03:02 and type 1 diabetes. Four previously
      unidentified associations were identified across the spectrum of disease with two
      and four-digit HLA alleles and 10 with nonsynonymous variants. Some conditions
      associated with multiple HLA variants and stronger associations with more severe
      disease manifestations were identified. A comprehensive, publicly available
      catalog of clinical phenotypes associated with HLA variation is provided.
      Examining HLA variant disease associations in this large data set allows
      comprehensive definition of disease associations to drive further mechanistic
      insights.

PMID- 28490675
TI  - Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc
      Concentration.
AB  - Background: Plasma or serum zinc concentration (PZC or SZC) is the primary
      measure of zinc status, but accurate sampling requires controlling for hemolysis
      to prevent leakage of zinc from erythrocytes. It is not established how much
      hemolysis can occur without changing PZC/SZC concentrations.Objective: This study
      determines a guideline for the level of hemolysis that can significantly elevate
      PZC/SZC.Methods: The effect of hemolysis on PZC/SZC was estimated by using
      standard hematologic variables and mineral content. The calculated hemolysis
      threshold was then compared with results from an in vitro study and a population
      survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct
      spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron
      concentrations were determined by inductively coupled plasma
      spectrometry.Results: A 5% increase in PZC/SZC was calculated to result from the
      lysis of 1.15% of the erythrocytes in whole blood, corresponding to ~1 g
      hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated
      hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin
      concentrations reached 1.18 +/- 0.10 g/L. In addition, serum samples from a
      population nutritional survey were scored for hemolysis and analyzed for changes
      in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an
      estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach
      indicated that a 5% increase in PZC/SZC occurs at ~1 g hemoglobin/L in plasma or
      serum. This concentration of hemoglobin can be readily identified directly by
      chemical hemoglobin assays or indirectly by direct spectrophotometry or matching
      to a color scale.Conclusions: A threshold of 1 g hemoglobin/L is recommended for
      PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of
      this threshold may improve zinc assessment for monitoring zinc status and
      nutritional interventions.

PMID- 28490676
TI  - Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or
      without Artificial Gravity.
AB  - Background: Zinc and copper have many physiologic functions and little or no
      functional storage capability, so persistent losses of either element present
      health concerns, especially during extended-duration space missions.Objectives:
      We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on
      copper and zinc metabolism to better understand the role of these nutrients in
      human adaptation to (simulated) spaceflight. We also investigated the effect of
      artificial gravity on copper and zinc homeostasis.Methods: Zinc and copper
      balances were studied in 15 men [mean +/- SD age: 29 +/- 3 y; body mass index (in
      kg/m2): 26.4 +/- 2.2] before, during, and after 21 d of head-down tilt BR, during
      which 8 of the participants were subjected to artificial gravity (AG) by
      centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge
      but were not exposed to centrifugation. The study was conducted in a metabolic
      ward; all urine and feces were collected. Data were analyzed by 2-factor repeated
      measures ANOVA.Results: Urinary zinc excretion values for control and AG groups
      were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc
      excretion values for control and AG groups were 36% and 19%, respectively, higher
      during BR, resulting in 67% and 82% lower net zinc balances for controls and AG,
      respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal
      copper values for control and AG groups were 40% and 33%, respectively, higher
      during BR than before BR (P < 0.01 for both). Urinary copper did not change
      during BR, but a 19% increase was observed after BR compared with before BR in
      the AG group (P < 0.05).Conclusions: The increased fecal excretion of copper and
      zinc by men during BR suggests that their absorption of these minerals from the
      diet was reduced, secondary to the release of minerals from bone and muscle.
      These findings highlight the importance of determining dietary requirements for
      astronauts on space missions and ensuring provision and intake of all nutrients.

PMID- 28490678
TI  - Implications of US Nutrition Facts Label Changes on Micronutrient Density of
      Fortified Foods and Supplements.
AB  - The US FDA published new nutrition-labeling regulations in May 2016. For the
      first time since the implementation of the Nutrition Labeling and Education Act
      of 1990, the Daily Value (DV) for most vitamins will change, as will the units of
      measurement used in nutrition labeling for some vitamins. For some food
      categories, the Reference Amounts Customarily Consumed (RACCs) will increase to
      reflect portions commonly consumed on a single occasion. These regulatory changes
      are now effective, and product label changes will be mandatory beginning 26 July
      2018. This commentary considers the potential impact of these regulatory changes
      on the vitamin and mineral contents of foods and dietary supplements. Case
      studies examined potential effects on food fortification and nutrient density.
      The updated DVs may lead to a reduction in the nutrient density of foods and
      dietary supplements with respect to 8 vitamins (vitamin A, thiamin, riboflavin,
      niacin, vitamin B-6, vitamin B-12, biotin, and pantothenic acid) and 6 minerals
      (zinc, selenium, copper, chromium, molybdenum, and chloride), and have mixed
      effects on 2 vitamins where the amount required per serving is affected by
      chemical structure (i.e., form) (natural vitamin E compared with synthetic
      vitamin E and folic acid compared with folate). Despite an increased DV for
      vitamin D, regulations limit food fortification. The adoption of Dietary Folate
      Equivalents for folate labeling may lead to reductions in the quantity of folic
      acid voluntarily added per RACC. Finally, because of increased RACCs in some food
      categories to reflect portions that people typically eat at one time, the vitamin
      and mineral density of these foods may be affected adversely. In totality, the
      United States is entering an era in which the need to monitor dietary intake
      patterns and nutritional status is unprecedented.

PMID- 28490677
TI  - Dietary Human Milk Oligosaccharides but Not Prebiotic Oligosaccharides Increase
      Circulating Natural Killer Cell and Mesenteric Lymph Node Memory T Cell
      Populations in Noninfected and Rotavirus-Infected Neonatal Piglets.
AB  - Background: Human milk oligosaccharides (HMOs) have antimicrobial and
      immunomodulatory actions. It has previously been reported that these
      oligosaccharides contribute to the reduced duration of rotavirus-induced diarrhea
      in pigs.Objective: We measured the effects of HMOs and prebiotic oligosaccharides
      on immune cell populations from noninfected and rotavirus-infected pigs. We
      hypothesized that dietary HMOs would modulate systemic and gastrointestinal
      immunity.Methods: Colostrum-deprived newborn pigs were fed formula, formula with
      4 g HMOs/L (2'-fucosyllactose, lacto-N-neotetraose, 6'-sialyllactose, 3'
      sialyllactose, and free sialic acid), or formula with 3.6 g short-chain
      galactooligosaccharides/L and 0.4 g long-chain fructooligosaccharides/L. On day
      10, half of the pigs were infected with the porcine rotavirus strain OSU.
      Peripheral blood mononuclear cell (PBMC), mesenteric lymph node (MLN), and ileal
      Peyer's patch immune cell populations were assessed with the use of flow
      cytometry 5 d postinfection. Interferon-gamma (IFN-gamma)-producing cells were
      assessed with the use of Enzyme-Linked ImmunoSpot assay.Results: Infection
      changed immune cell populations with more systemic natural killer (NK) cells,
      memory effector T cells, and major histocompatibility complex II+ cells in
      infected than noninfected pigs (P < 0.06). Regardless of infection status, HMO
      fed pigs had nearly twice as many PBMC NK cells, 36% more MLN effector memory T
      cells, and 5 times more PBMC basophils than formula-fed pigs (P < 0.04). These
      populations were intermediate in pigs fed prebiotics. PBMCs from HMO-fed
      noninfected pigs had twice as many IFN-gamma-producing cells as did those from
      formula-fed noninfected pigs (P = 0.017). The PBMCs and MLNs of formula-fed
      noninfected pigs had 3 times more plasmacytoid dendritic cells (pDCs) than those
      of HMO-fed noninfected and formula-fed infected pigs (P < 0.04). In the MLNs, the
      formula-fed noninfected pigs had more macrophages, pDCs, and mature DCs (P <
      0.04) but fewer immature DCs than HMO-fed noninfected pigs (P =
      0.022).Conclusions: Dietary HMOs were more effective than prebiotics in altering
      systemic and gastrointestinal immune cells in pigs. These altered immune cell
      populations may mediate the effects of dietary HMOs on rotavirus infection
      susceptibility.

PMID- 28490679
TI  - [Issues on the Intraoperative Motor Evoked Potential Monitoring in Neurosurgery].

PMID- 28490680
TI  - [A Ruptured Aneurysm at the Origin of a Duplicated Middle Cerebral Artery,
      Treated by Coil Embolization:A Case Report].
AB  - Duplication of the middle cerebral artery(MCA)is an anatomical variant of the
      MCA, originating from the distal portion of the internal carotid artery(ICA)and
      supplying blood flow to the tip of the temporal lobe. Cerebral aneurysms rarely
      develop at the bifurcation of the ICA and the duplicated MCA, but when they do
      develop, they may result in subarachnoid hemorrhage. We treated a 41-year-old
      man, who was urgently brought to our hospital because of severe headache. A
      computed tomography(CT)scan showed subarachnoid hemorrhage due to the rupture of
      an aneurysm at the origin of the duplicated MCA. The aneurysm was small and
      projected laterally, and coil embolization was performed employing a balloon
      catheter. The neck of the aneurysm was not embolized to preserve the origin of
      the duplicated MCA. The patient had an uneventful postoperative course, and he
      returned to his usual daily activities. Coil embolization is rapidly developing
      for treatment of cerebral aneurysms and may be the first-line treatment for
      duplicated MCA aneurysms. Owing to the relatively small size of such aneurysms,
      the risk of intraprocedural rupture should be considered, and a carefully
      performed balloon-assisted procedure is recommended.

PMID- 28490681
TI  - [Hemorrhagic Onset of Subependymal Giant Cell Astrocytoma Associated with
      Tuberous Sclerosis:A Case Report and Review of Literature].
AB  - We report on a case of subependymal giant cell astrocytoma(SEGA)in a patient with
      tuberous sclerosis(TSC)that presented with intratumoral hemorrhage and acute
      hydrocephalus. Initial treatment was external ventricular drainage to control the
      intracranial pressure;however, the tumor increased in size due to recurrent
      hemorrhage. Subsequently, the tumor was successfully removed via the
      transcortical-transventricular approach without neurological deterioration.
      Although intratumoral hemorrhage is extremely rare in patients with SEGA,
      subsequent acute hydrocephalus resulting from obstruction of the foramen of Monro
      will be fatal if prompt surgical treatment is not available. Careful and
      periodical radiographic examination of the central nervous system will be
      mandatory in patients with TSC, especially in those who have subependymal
      nodules(SEN)or SEGA around the foramen of Monro. Radical surgical removal should
      be considered before they become symptomatic.

PMID- 28490682
TI  - [Association of Lower limb Neuropathy with Lumboperitoneal Shunt Transection:A
      Case Report].
AB  - A 49-year-old woman suffered hydrocephalus after subarachnoid hemorrhage, and
      underwent a lumboperitoneal(LP)shunt operation. X-ray imaging revealed that a
      spinal catheter inserted into the cranial side from L2/3 turned caudally at the
      Th12 level. Postoperative numbness and pain of the left buttocks and posterior
      femoral region persisted. The spinal catheter was pulled about 5 cm to improve
      flexure, and was reconnected 10 months after the shunt procedure. Symptoms
      improved, but a similar symptom developed one and a half years later. The spinal
      catheter was torn at the connection to the shunt valve. The catheter curved to
      the left side of the spinal cord and the catheter tip was located around the
      right Th12/L1 intervertebral foramen. We continued observations with analgesics,
      but symptoms did not subside. The shunt was removed 16 months after symptom
      relapse, and symptoms disappeared immediately. Bent insertion of the lumbar
      catheter is a potential cause of lower limb neuropathy after LP shunt operation.
      Attention must also be paid to the continuity of the catheter in follow-up after
      shunt procedures.

PMID- 28490683
TI  - [Concomitant Surgery for Symptomatic Severe Carotid Artery Stenosis and Aortic
      Valve Stenosis with Contralateral Internal Carotid Artery Occlusion:A Case
      Report].
AB  - We report a case of concomitant carotid endarterectomy(CEA)and aortic valve
      replacement(AVR)for symptomatic severe carotid artery and aortic valve
      stenosis(AS). A 77-year-old man, presented to our hospital with AS complicated by
      right internal carotid artery(ICA)stenosis and left ICA occlusion, seeking
      treatment for AS. He suffered from left hemiparesis, and diffusion-weighted
      magnetic resonance imaging(MRI)showed multiple ischemic lesions in the right
      cerebral hemisphere. He was admitted to our neurosurgical department and received
      treatment for acute cerebral infarction caused by severe right ICA stenosis. The
      symptomatic severe right ICA stenosis was an indication for surgical treatment,
      but simple carotid revascularization of the stenosed ICA was considered to be
      deteriorated the cardiac function due to untreated AS. Thus, we decided to
      perform concomitant carotid and valvular surgery. The patient underwent a
      combined CEA and AVR procedure with the introduction of an intraoperative intra
      aortic balloon pump. His postoperative course was uneventful even 12 months after
      the surgery. Management and surgical strategies for patients with concomitant ICA
      stenosis and AS continue to be controversial subjects. Combined carotid and
      cardiac valve surgery is considered to be effective in such cases, and we discuss
      its implications and review of literature.

PMID- 28490684
TI  - [Cerebral Venous Sinus Thrombosis Following Cisplatin-Based Chemotherapy for
      Testicular Tumor].
AB  - A man in his 30s who presented with an enlarged right testicle was diagnosed with
      a germ cell tumor via orchiectomy. Adjuvant chemotherapy with cisplatin,
      etoposide and bleomycin(BEP)was initiated. He developed a headache 8 days later,
      followed by neurological deficits 10 days later. Magnetic resonance
      imaging(MRI)and magnetic resonance venography(MRV)showed thrombotic occlusion at
      the superior sagittal sinus. Anticoagulant therapy with heparin was initiated.
      However, a generalized epileptic seizure occurred 11 days later, and an
      antiepileptic drug therapy was initiated. The headache and neurological deficits
      gradually improved, and MRI findings showed that the superior sagittal sinus had
      re-canalized. The main cause of the sinus thrombosis in this patient was
      considered dehydration and cisplatin-induced hypercoagulability. Five courses of
      BEP therapy were carried out with care to avoid dehydration. The patient has
      remained free of testicular tumor recurrence, metastasis, and cerebral sinus
      thrombosis for 2 years. Cisplatin-based chemotherapy is an established risk
      factor for venous thromboembolism(VTE), and cerebral sinus thrombosis is a rare
      but dangerous complication. Therefore, cerebral sinus thrombosis should be
      considered when patients with testicular cancer who undergo cisplatin-based
      chemotherapy start to develop neurological symptoms. Clinicians should be aware
      of this treatable complication.

PMID- 28490685
TI  - [Ruptured C2 Aneurysm of the Internal Carotid Artery with Ipsilateral Unruptured
      Giant Internal Carotid Artery Aneurysm:A Case Report].
AB  - A giant intracranial internal carotid artery(ICA)aneurysm is difficult to treat.
      We encountered a case with an unruptured giant intracranial ICA aneurysm with a
      ruptured C2 aneurysm of the ipsilateral ICA. In this case report, we describe how
      the treatment and review the literature. A 59-year-old man presented with sudden
      onset headache and vomiting. He was diagnosed at a local neurosurgical unit as
      having a subarachnoid hemorrhage and admitted to our hospital. Cerebral angiogram
      revealed an unruptured giant ICA C3-4 aneurysm with a ruptured aneurysm of the
      ipsilateral ICA C2. The ruptured aneurysm had a wide neck and was located in the
      medial wall of the ICA C2;it was difficult to perform neck clipping or coil
      embolization. We performed a high-flow bypass using a radial artery graft
      followed by trapping of the left ICA. Postoperative imaging showed no new
      ischemic damage, and the patency of bypass flow was good. The left ophthalmic
      artery was perfused from the external carotid artery. Although the patient
      experienced incomplete left oculomotor nerve palsy and left lower
      quadrantanopsia, his neurological function had recovered within a year, and he
      was able to resume his previous work. High-flow bypass with ICA trapping is
      effective for ICA giant aneurysm. Attention to postoperative ophthalmic function
      and oculomotor symptoms is important.

PMID- 28490686
TI  - [A Case of Meralgia Paresthetica Treated with Neurolysis].
AB  - A 60-year-old woman presented with a 1-year history of pain and numbness in the
      left anterolateral thigh. The symptoms aggravated on walking and standing. Her
      visual analogue scale(VAS)score was 7.1/10. Tinel's like sign was positive over
      the lateral femoral cutaneous nerve(LFCN), in the inguinal ligament region. LFCN
      block at the trigger point, in the inguinal ligament, resulted in relief of the
      symptoms and we diagnosed meralgia paresthetica(MP), which is the entrapment
      neuropathy of the LFCN. Initially, we performed observation therapy with oral
      medication and LFCN blocks. However, these treatments failed to relieve the
      symptoms. Therefore, we performed neurolysis with a microscope under local
      anesthesia. The symptoms improved immediately after surgery and her VAS score of
      thigh symptom improved from 7.1 to 1.9 after 3 months. Conservative and surgical
      treatment for MP generally yield good outcome and we should pay attention to the
      MP as a differential diagnosis for thigh numbness and pain.

PMID- 28490687
TI  - [Association between Glioblastoma with Oligodendroglioma Component and
      Subcortical Hemorrhage:A Case Report].

PMID- 28490688
TI  - [Pre- and Intra-Operative Supporting Technology for Brain Tumors(7)Surgery for
      Cerebellopontine Angle Brain Tumors].

PMID- 28490689
TI  - Patient-derived cells modeling pediatric glioma.

PMID- 28490691
TI  - The puzzling interplay between p53 and Sp1.

PMID- 28490690
TI  - A decline in female baboon hypothalamo-pituitary-adrenal axis activity
      anticipates aging.
AB  - Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate
      multiple processes that determine the aging trajectory. Debate exists regarding
      life-course circulating glucocorticoid concentrations. Rodent and nonhuman
      primate studies indicate circulating glucocorticoids fall from early life. We
      measured fasting morning cortisol in 24 female baboons (6-21 years, human
      equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN)
      arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors,
      and pituitary proopiomelanocortin immunohistochemically in 14 of these females at
      6-13 years. We identified significant age-related 1) linear fall in cortisol and
      PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and
      mineralocorticoid receptors; 3) increased PVN 11beta-hydroxysteroid dehydrogenase
      1 and 2, regulators of local cortisol production, and 4) decreased pituitary
      proopiomelanocortin. Our data identify increased age-related negative feedback
      and local PVN cortisol production as potential mechanisms decreasing PVN drive to
      hypothalamo-pituitary-adrenal axis activity that result in the age-related
      circulating cortisol fall. Further studies are needed to determine whether the
      cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an
      epiphenomenon unrelated to aging processes. We conclude that aging processes are
      best studied by linear life-course analysis beginning early in life.

PMID- 28490692
TI  - [Identification of the interacting proteins with S100A8 or S100A9 by affinity
      purification and mass spectrometry].
AB  - OBJECTIVE: To identify the interacting proteins with S100A8 or S100A9 in HEK293
      cell line by flag-tag affinity purification and liquid chromatography mass
      spectrometry/mass spectrometry (LC-MS/MS).? Methods: The p3*Flag-CMV-S100A8 and
      p3*Flag-CMV-S100A9 expression vectors were constructed by inserting S100A8 or
      S100A9 coding sequence. The recombinant plasmids were then transfected into
      HEK293 cells. Affinity purification and LC-MS/MS were applied to identify the
      proteins interacting with S100A8 or S100A9. Bioinformatics analysis was used to
      seek the gene ontology of the interacting proteins. Co-immunoprecipitation (Co
      IP) was applied to confirm the proteins interacted with S100A8 or S100A9.?
      Results: Fourteen proteins including pyruvate kinase, muscle (PKM), nucleophosmin
      (NPM1) and eukaryotic translation initiation factor 5A (EIF5A), which potentially
      interacted with S100A8, were successfully identified by Flag-tag affinity
      purification followed by LC-MS/MS analysis. Six proteins, such as tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (14-3
      3epsilon) and PKM, which potentially interacted with S100A9, were successfully
      identified. Gene ontology analysis of the identified proteins suggested that
      proteins interacted with S100A8 or S100A9 were involved in several biological
      pathways, including canonical glycolysis, positive regulation of NF-kappaB
      transcription factor activity, negative regulation of apoptotic process, cell
      cell adhesion, etc. Co-IP experiment confirmed that PKM2 can interact with both
      S100A8 and S100A9, and 14-3-3epsilon can interact with S100A8.? Conclusion: PKM2
      is identified to interact with both S100A8 and S100A9, while 14-3-3epsilon can
      interact with S100A9. These results may provide a new clue for the role of S100A8
      or S100A9 in the progression of colitis-associated colorectal cancer.

PMID- 28490693
TI  - [Comparison of differentiated endothelial cells from the embryonic stem cells
      with human umbilical vein endothelial cells].
AB  - OBJECTIVE: To compare the differentiated endothelial cells from the embryonic
      stem cells in vitro with human umbilical vein endothelial cells (HUVECs).?
      Methods: Induction of the stem cells HUES9 to endothelial cells follows 2 steps.
      Stem cells were treated with CHIR99021 (10 umol/L) and bone morphogenetic protein
      4 (25 ng/mL) for 3 days to keep mesoderm state, then subsequent exposure them to
      VEGF165 (200 ng/mL) and Forskolin (2 umol/L) to differentiate into endothelial
      cells. The morphology of differentiated endothelial cells were compared with
      HUVECs. The surface marker CD144 on differentiated cells and HUVECs were
      detected. The capabilities of two types of endothelial cells in migration and
      angiogenesis were examined.? Results: The differentiated endothelial cells show
      the same morphology with HUVECs. After 6 days of differentiation, the efficiency
      reached 73.4%. The positive percentage of CD144 for the differentiated
      endothelial cells and HUVECs was 86.6% and 94.4%, respectively. Both of them show
      capabilities of migration and angiogenesis, especially when they were treated
      with SB431542 to inhibit TGF-beta signal pathway.? Conclusion: The method for
      induction of stem cells to endothelial cells is productivity and it can be used
      for further study.

PMID- 28490694
TI  - [Effect of acupuncture combined with hypothermia on MAPK/ERK pathway and
      apoptosis related factors in rats with cerebral ischemia reperfusion injury].
AB  - OBJECTIVE: To observe effect of acupuncture combined with hypothermia therapy on
      MAPK/ERK pathway and apoptosis related factorsin rats suffered cerebral ischemia
      reperfusion and to explore underlying mechanisms.? Methods: Middle cerebral
      artery ischemia model were established.Ninety SD rats were randomly assigned into
      a blank group, a control group, a model group, an acupuncture group, a mild
      hypothermia group, and an acupuncture with hypothermia group. After 72 h
      treatment, nerve function defect scores were observed, and infarction area
      percent was detected by 2, 3, 5-triphenyl-2H-tetrazolium chloride (TTC) staining;
      expressions of Bcl-2 and Bax were examined by immunohistochemistry; apoptotic
      cells were detected by TUNEL assay; and expression levels of phospho-mitogen
      activated protein kinase(p-MEK2) and phospho-extracellular signal regulated
      kinase 1/2 (p-ERK1/2) in the rats' hippocampus ischemic side were determined by
      Western blot.? Results: In the rats of the model group, the neural function
      defect scores, the infarction area percent, the expression level of Bax, and
      apoptotic cells increased, while the level of Bcl-2 decreased significantly. The
      level of p-MEK2 and p-ERK1/2 increased obviously compared with the blank and
      control groups (P<0.05 or P<0.01). After treatment with acupuncture and
      hypothermia, the neural function defect scores, infarction area percent, and the
      level of Bax, apoptotic cells and the levels of p-MEK2 and p-ERK1/2 were
      significantly decreased, while the level of Bcl-2 in the treatment group was
      significantly elevated (P<0.05 or P<0.01) compared with the model group. Compared
      with the acupuncture group or the hypothermia group, the neural function defect
      scores and the levels of p-MEK2 and p-ERK1/2 in the acupuncture combined with
      hypothermia group were significantly reduced (P<0.05 or P<0.01).? Conclusion:
      Acupuncture and hypothermia therapy can improve cerebral function, and reduce the
      cerebral injury through down-regulation of Bax level, and up-regulation of Bcl-2
      level, which is related to reducing the levels of p-MEK2 and p-ERK1/2. The
      therapeutic effects on cerebral ischemia reperfusion injury for combination of
      acupuncture with hypothermia are better than those with single application of
      acupuncture or hypothermia.

PMID- 28490695
TI  - [Effect of hydrogen sulfide on inducible nitric oxide synthase in kidneys of Type
      1 diabetic rats].
AB  - OBJECTIVE: To investigate effects of hydrogen sulfide (H2S) on inducible nitric
      oxide synthase (iNOS) in kidneys of Type 1 diabetic rats.? Methods: Thirty-two
      male SD rats were randomly divided into four groups: A normal control (NC) group,
      a diabetes mellitus (DM) group, a NaHS (NaHS+DM) group, and a NaHS control (NaHS)
      group (n=8 per group). Type 1 diabetes was induced by a single intraperitoneal
      injection of streptozotocin (55 mg/kg). After successful establishment of models,
      the rats in NaHS+DM and NaHS groups were injected with NaHS solution (56
      MUmol/kg) intraperitoneally. Eight weeks later, the activities of total nitric
      oxide synthase (T-NOS) and iNOS, as well as the level of nitric oxide (NO) were
      detected in serum and renal tissues, respectively. The activity of glutathione
      peroxidase (GSH-Px) was determined in renal tissues. The ultrastructures of renal
      tissues were observed by transmission electron microscope. The protein expression
      of iNOS in renal tissues was detected by Western blot.? Results: Compared with
      the NC group, there was no significant difference in the various indexes in the
      NaHS group (P>0.05). However, in the DM group, the activities of T-NOS and iNOS,
      and the level of NO were all increased significantly in serum and renal tissues,
      while the activity of GSH-Px was decreased in renal tissues. Under the electronic
      microscope, the thickening of the glomerular capillary basement membrane, the
      proliferation of mesangial matrix, and the foot fusion were observed. The protein
      expression of iNOS was increased obviously in renal tissues in the DM group
      (P<0.01). Compared with the DM group, the activities of T-NOS and iNOS and the
      level of NO were all decreased in serum and renal tissues, while the activity of
      GSH-Px was increased in renal tissues in the NaHS+DM group (P<0.01). The renal
      ultrastructural damages were ameliorated obviously. The protein expression of
      iNOS was decreased significantly (P<0.01).? Conclusion: H2S exerts a protective
      effect on kidney injury in type 1 diabetic rats. The mechanism might be related
      to inhibition of iNOS activity and protein expression, in turn leading to
      reduction of NO content in renal tissues.

PMID- 28490696
TI  - [Diagnostic value of renal phospholipase A2 receptor and serum anti-phospholipase
      A2 receptor antibody in membranous nephropathy].
AB  - OBJECTIVE: To examine the expression of phospholipase A2 receptor (PLA2R) in
      renal tissues and the level of anti-PLA2R antibody in serum in patients with
      idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy
      (SMN), and to evaluate their diagnostic value in IMN.? Methods: A total of 73
      patients, who were diagnosed between May, 2014 and February, 2015 in the
      Department of Nephrology of the Second Xiangya Hospital, Central South
      University, were divided into three groups: an IMN group (n=48), an SMN group
      (n=17) and a minimal change disease group (n=8) according to the renal biopsy.
      PLA2R expression in renal tissues and the level of anti-PLA2R antibody in serum
      were detected by indirect immunofluorescence technique.? Results: The positive
      rate and fluorescence intensity for PLA2R in the renal tissues in the IMN group
      were higher than those in the SMN group (91.7% in the IMN group vs 29.4% in the
      SMN group, P<0.05), while the positive rate and serum level for anti-PLA2R
      antibody in the IMN group were higher than those in the SMN group (85.4% in the
      IMN group vs 29.4% in the SMN group, P<0.05); the expression of PLA2R in renal
      tissues and the serum level for anti-PLA2R antibody were not detected in the
      minimal change disease group. The serum level of anti-PLA2R antibody was
      positively correlated with 24 h urine protein (r=0.432, P<0.01) and negatively
      correlated with serum albumin (r=-0.307, P<0.05).? Conclusion: The expression of
      PLA2R in renal tissues and the serum level of anti-PLA2R antibody might be
      potential markers for diagnosis of IMN.

PMID- 28490697
TI  - [Effect of left ventricular hypertrophy and deformation on cardiac function in
      patients with uremia cardiomyopathy by using quantitative speckle tracking
      technology].
AB  - OBJECTIVE: To evaluate the effect of left ventricular hypertrophy and deformation
      on cardiac function in patients with uremic cardiomyopathy (UCM) by using the
      technology of two dimensional speckle tracking imaging (2D-STI).? Methods: A
      total of 67 UCM patients were randomly divided into the normal cardiac function
      group (subgroup A, 32 cases) and the abnormal cardiac function group (subgroup B,
      35 cases) according to the New York Heart Association points (NYHA-P). A total of
      30 healthy subjetcs served as the control group. Parameters including left
      ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left
      ventricular spherical index (LVSI), left ventricular myocardial mean radial
      strain (MRS), mean radial strain rate (MRSR), mean longitudinal strain (MLS),
      local systolic twist angle (STA), and mitral annulus maximum displacement (TMAD)
      were detected.? Results: MLS, MRS, MRSR, LVSI, STA and TMAD in the Group A and
      Group B were lower than that in the control group (P<0.05), and LVMI in the Group
      A and Group B was increased than those in the control group (P<0.05); LVEF, MLS,
      MRS, MRSR, LVSI and STA in the Group B was decreased than that in the Group A
      (P<0.05). MLS in the Group A and B were positively correlated with LVEF and LVSI,
      but negatively correlated with LVMI. Using the point of 14.10% for MLS to
      evaluate UCM patients with NYHA-P>4 points, the sensitivity, the specificity and
      Yuedden index were 90.5%, 71% and 0.585, respectively. STA in UCM patients were
      lower than that in the control (P<0.05).? Conclusion: 2D-STI possesses a unique
      advantage in detecting left ventricular strain and strain rate on left
      ventricular regional function in UCM with left ventricular hypertrophy and
      ventricular deformation. There is no direct correlation between the left
      ventricular hypertrophy and ventricular deformation, but the ventricular
      hypertrophy and deformation are correlated with regional cardiac function and
      clinical cardiac function. Left ventricular regional dysfunction may occur before
      cardiac hypertrophy and deformation.

PMID- 28490698
TI  - [Diagnosis and differential diagnosis for solitary fibrous tumor in the abdomen
      and pelvis by CT].
AB  - OBJECTIVE: To study the CT features for solitary fibrous tumor (SFT) in the
      abdomen and pelvis and to improve the diagnostic accuracy.? Methods: Fourteen
      patients with SFT were collected in our hospital from January, 2011 to December,
      2015. Characteristic of images were analyzed and compared for 10 SFT, which
      located outside the abdominal organs with extragastrointestinal stromal tumors
      (EGIST), leiomyosarcoma, and schwannoma.? Results: Necrosis and cystic formation
      were frequently present in SFT in the abdomen and pelvis. CE-CT showed serpentine
      vessels along the periphery, while pattern of enhancement was map-like
      inhomogeneous progressive. Comparing with the EGIST or schwannoma, the difference
      of CT value in non-contrast and the arterial phase were statistically significant
      (P<0.05). The numbers of peritumoral circuity vessel were significantly different
      between SFT and EGIST (chi2=18.27, P<0.008) or between SFT and schwannoma
      (chi2=19.25, P<0.008). Comparing with the leiomyosarcoma or schwannoma, SFT
      located outside the abdominal organs. We found that tumor necrosis rate was
      significantly different between SFT and leiomyoscarcoma (chi2=8.00, P<0.008).?
      Conclusion: SFT in the abdomen and pelvis show certain CT characteristics. The CT
      value in non-contrast and at the arterial phase, tumor necrosis rate, and
      serpentine vessels along the periphery were pivotal in differentiating SFT from
      leiomyosarcoma, EGIST and schwannoma.

PMID- 28490699
TI  - [Effect of tumor volume on pulmonary dose-volume parameter by intensity-modulated
      radiation therapy in non-small cell lung cancer].
AB  - OBJECTIVE: To explore the effectof tumor volume on pulmonary dose-volume
      parameters by intensity-modulated radiation therapy (IMRT) in non-small cell lung
      cancer (NSCLC), and to provide a basis for pulmonary dose parameters in IMRT
      treatment.? Methods: A total of 204 patients with NSCLC received IMRT were
      retrospectively analyzed from June, 2009 to October, 2013. The prescribed dose of
      planning target volume (PTV) for primary tumor was 60-66Gy (2.00-2.25 Gy, 27-33
      times in all). The fractional volume percent of the lung received a dose >5 or 20
      Gy (V5, V20), and absolute volume of lung received a dose <5 Gy (AVS5).The mean
      lung dose (MLD) in normal tissues were analyzed. Regression model curve was used
      to analyze them along with the change of primary tumor volume.? Results: With the
      increase in lung tumor volume, the V5, V20 and MLD presented quadratic equation
      curve, and AVS5 presented logarithmic equation. When the tumor volume, less than
      a certain value (294.6, 283.2, 304.9 cm3, respectively), the V5, V20 and MLD
      increased with tumor size and presented an increased quadratic curve; when the
      tumor volume was higher than a certain value (294.6, 283.2, 304.9 cm3
      respectively), the V5, V20 and MLD was declined. The AVS5 was declined in a
      logarithmic curve along with the increase of tumor volume.? Conclusion: With the
      increase in lung tumor volume, the change in rule of V5, V20, MLD and AVS5 is not
      completely equivalent. When the tumor volume exceeds a certain boundary value
      (about 300 cubic centimeter), the corresponding tumor diameter is about 7-8 cm.
      In addition to the focus on pulmonary V5, V20 and MLD, we should also pay more
      attention to AVS5 restrictions in establishment of IMRT in NSCLC.

PMID- 28490700
TI  - [Role of TGF-beta1 in multi-drug resistance in small cell lung cancer and its
      clinical significance].
AB  - OBJECTIVE: To investigate the role of transforming growth factor beta1 (TGF
      beta1) in multi-drug resistance in small cell lung cancer and its clinical
      significance.? Methods: The mRNA and protein expressions of TGF-beta1 in H69 and
      H69AR cells were detected by real-time PCR and Western blot, respectively. After
      silence of TGF-beta1, the sensitivity of H69AR to drugs was detected by CCK8
      assay. The expressions of TGF-beta1 in lung cancer and paracarcinoma tissues were
      examined by QRT-PCR and immunohistochemistry. The relationship of TGF-beta1
      expression with clinical pathological features and prognosis of patients was
      studied.? Results: Compared to H69, the mRNA and protein expressions of TGF-beta1
      in H69AR cells were significantly increased by (5.93+/-0.47) and (8.49+/-1.92)
      folds, respectively (P<0.01). Transfection of TGF-beta1 siRNA resulted in a
      decrease of TGF-beta1 expression by 70.432% in H69AR cells (F=21.20, P<0.01) and
      an increase insensitivity to chemotherapeutic agents of H69AR cells (t=4.576,
      P<0.05). Compare with the paracarcinoma tissues, the expression of TGF-beta1 was
      significantly increased in small cell lung cancer tissues (t=13.925, P<0.01),
      which was closely related with clinical stage, chemosensitivity and overall
      survival (all P<0.05), but not related with gender, age (both P>0.05).?
      Conclusion: TGF-beta1 is involved in the regulation of small cell lung cancer
      multidrug resistance, which may be a potential marker to evaluate the
      chemosensitivity and clinical prognostic for small cell lung cancer.

PMID- 28490701
TI  - [AdeABC efflux pump and resistance of Acinetobacter baumannii against
      carbapenem].
AB  - OBJECTIVE: To investigate relationship between AdeABC efflux pump and resistance
      of Acinetobacter baumannii against carbapenem.? Methods: Carbapenem-resistant
      strains were acquired from multistep selection resistance test by meropenem in
      vitro. The quantitation test for sensitivities of strains before and after
      induction was determined by the E-test, and carbonylcyanide-m
      chlorophenylhydrazone (CCCP) inhibition test was used to screen efflux pump. PCR,
      sequencing analysis, or real-time PCR was used to analyze the changes of
      regulatory genes adeR and adeS of the AdeABC efflux pump system, or expressions
      of adeA, adeB, adeR, and adeS in the strains before and after induction,
      respectively.? Results: The minimal inhibitory concentrations (MICs) of meropenem
      were at 0.38 MUg/mL and 0.25 MUg/mL in parental sensitive strain S25595 and
      S7257, respectively, and the MICs of meropenem for both S25595 and S7257 after
      induction were more than 32 MUg/mL. Compared with parental sensitive strains, the
      expression level of adeA, adeB, adeR, and adeS mRNA were elevated from 2.45 to
      9.44 times, but there were no gene mutations or insertion sequences in the
      regulatory gene adeS and adeR.? Conclusion: High expression of the AdeABC efflux
      pump system in Acinetobacter baumannii is closely associated with meropenem
      resistance. The upregulation of adeA and adeB expression is not due to gene
      mutations in the regulatory gene adeS and adeR and other mechanisms might account
      for it.

PMID- 28490702
TI  - [Status for self-medication based on bibliometric study in China].
AB  - OBJECTIVE: To figure out problems through analyzing the status for self
      medication in China and to provide references for further research.? Methods:
      Papers related to self-medication were collected from Chinese journal net
      database, Wanfang database, VIP database and China biomedical literature database
      (CBMDisc). A literature metrology analysis was carried out by NoteExpress 2.0 and
      Excel.? Results: A total of 161 papers were included in this study, while 33
      papers belong to Hubei and Jiangsu Province, accounting for 20.50% of the total
      amount of the papers. 22 papers were from journals as follows: China Pharmacy,
      Medicine and Society and Chinese Journal of Pharmacoepidemiology, accounting for
      13.67% of the total papers. 118 papers belong to research and experience discuss,
      accounting for 73.29% of all. The cooperation degree was 2.37, and 28 papers were
      funded. Domestic research reflected the current status of self-medication in our
      country. Although self-medication brought convenience for residents and reduce
      the burden on health system, it also brought a series of safety problems.?
      Conclusion: Self-medication gradually catches the attention of the researchers.
      Some researchers have paid attention to self medication, but the evidence is at a
      low level. Researchers should strengthen cooperation with interagency and carry
      out experimental study to promote further development for self-medication.

PMID- 28490703
TI  - [Construction of a psychological aging scale for healthy people].
AB  - OBJECTIVE: To construct a psychological aging scale, and to provide a tool and
      indexes for scientific evaluation on aging.? Methods: The age-related
      psychological items were collected through literature screening and expert
      interview. The importance, feasibilityand the degree of authority for the
      psychological index system were graded by two rounds of Delphi method. Using
      analytic hierarchy process, the weight of dimensions and items were determined.
      The analysis for internal consistency reliability, correlation and exploratory
      factor was performed to evaluate the reliability and validity of the scales.?
      Results: By two rounds of Delphi method, 17 experts offered the results as
      follows: the coefficient of expert authorities was 0.88+/-0.06, the coordination
      coefficients for the importance and feasibility in second round were 0.456
      (P<0.01) and 0.666 (P<0.01), respectively. The consistency was good. The
      psychological aging scale for healthy people included 4 dimensions as follows:
      cognitive function, emotion, personality and motivation. The weight coefficients
      for the 4 dimensions were 0.338, 0.250, 0.166 and 0.258, respectively. The
      Cronbach's alpha coefficient for the scale was 0.822, the reliability was 0.817,
      the content validity index (CVI) was 0.847, and the cumulative contribution rate
      for the 5 factors was51.42%.? Conclusion: The psychological aging scale is
      satisfied, which can provide reference for the evaluation for aging. The
      indicators were representative and well-recognized.

PMID- 28490704
TI  - [Establishement for regional pelvic trauma database in Hunan Province].
AB  - OBJECTIVE: To establish a database for pelvic trauma in Hunan Province, and to
      start the work of multicenter pelvic trauma registry.? Methods: To establish the
      database, literatures relevant to pelvic trauma were screened, the experiences
      from the established trauma database in China and abroad were learned, and the
      actual situations for pelvic trauma rescue in Hunan Province were considered. The
      database for pelvic trauma was established based on the PostgreSQL and the
      advanced programming language Java 1.6.? Results: The complex procedure for
      pelvic trauma rescue was described structurally. The contents for the database
      included general patient information, injurious condition, prehospital rescue,
      conditions in admission, treatment in hospital, status on discharge, diagnosis,
      classification, complication, trauma scoring and therapeutic effect. The database
      can be accessed through the internet by browser/servicer. The functions for the
      database include patient information management, data export, history query,
      progress report, video-image management and personal information management.?
      Conclusion: The database with whole life cycle pelvic trauma is successfully
      established for the first time in China. It is scientific, functional, practical,
      and user-friendly.

PMID- 28490705
TI  - [Spatial distribution and clustering in birth defects from 2010 to 2013 in
      Shaanxi Province].
AB  - OBJECTIVE: To explore the spatial distribution and clustering in birth defects
      from 2010 to 2013 in Shaanxi Province.? Methods: Spatial distribution was used to
      describe the birth defects, while ordinary Kriging method was used to predict the
      status of birth defects in Shaanxi province. The spatial characteristics for the
      birth defects at the county/district level were analyzed by spatial
      autocorrelation.? Results: The overall incidence of birth defects was 219.196/10
      000; Birth defect did not appear to be a random distribution but show a
      significant spatial aggregation. Spatial interpolation predicted the geographic
      distribution for occurrence of birth defects in Shaanxi Province. Local
      autocorrelation analysis showed nine "hot spot areas" for birth defects, such as
      Qian County, Liquan County, Yongshou County, Bin County, Fufeng County, Jingyang
      County, Chunhua County, Wugong County and Xingping City, and seven "cold spot
      areas" including Jia County, Yuyang District, Mizhi County, Suide County, Wubu
      County, Qingjian County and Zizhou District.? Conclusion: There are spatial
      clustering in birth defects from 2010 to 2013 in Shaanxi Province. Spatial
      interpolation and spatial autocorrelation can be used to predict the spatial
      features of birth defects in the whole province and provide evidence for the
      further intervention.

PMID- 28490706
TI  - [Progress of the application of stem cell therapy for end-stage liver disease].
AB  - Many risk factors lead to hypohepatia and hepatic failure, causing people
      suffering from end-stage liver disease. The conventional treatment for end-stage
      liver disease is not good enough. Orthotopic liver transplantation is effective.
      However, the high cost, lack of liver source, immune rejection and other factors
      limit the large-scale clinical application. Thus, cell therapy is a good option.
      Studies on common cell sources for the treatment of liver disease and the
      induction of hepatocytes by embryonic stem cells or pluripotent stem cells have
      made progress. With the development of stem cell technology, cell transplantation
      has become a new option, which brings hope to people with end-stage liver
      diseasetransplantation has become a new option. It brings hope to people with end
      stage liver disease.

PMID- 28490707
TI  - [Effect of NF-kappaB on the pathogenic course of non-alcoholic fatty liver
      disease].
AB  - With the economic growth and better standards of living, the prevalence of non
      alcoholic fatty liver disease (NAFLD) is expected to increase dramatically
      worldwide. NAFLD is a common chronic inflammation disease. NF-kappaB is a
      transcription factor that plays crucial roles in inflammation, immunity, cell
      proliferation and apoptosis. It can facilitate the occurrence and development of
      NAFLD, and the underlying mechanisms are related to insulin resistance, oxidative
      stress, alteration of intestinal flora, activation of renin angiotensin system,
      etc.

PMID- 28490708
TI  - [Advance in glutathione S-transferase kappa 1].
AB  - Glutathione S-transferase kappa 1 (GSTK1) is a key regulator for adiponectin
      secretion and multimerization. In Caenorhabditis elegans, GSTK1 is involved in
      energy production and lipid metabolism. Meanwhile, the GSTK1 level is negatively
      correlated with obesity. It may alleviate the endoplasmic reticulum stress
      mediated downregulation of adiponectin. Moreover, a polymorphism in human GSTK1
      promoter is related with insulin secretion and fat deposition. Therefore, GSTK1
      might be a novel target for the treatment of insulin resistance and the relevant
      metabolic diseases.

PMID- 28490709
TI  - [Research progress in mechanisms and clinical application for blonanserin and
      lurasidone in improving cognitive function of schizophrenia].
AB  - Cognition deficit is one of the most common symptoms of schizophrenia, including
      abstract thinking and memory, and attention deficits. Previous studies have
      suggested that the improvement of cognition is very important for the recovery of
      disease and social function for the patients. Recent studies indicated that two
      new atypical antipsychotics, blonanserin and lurasidone, are expected to improve
      the cognitive impairment in patients with schizophrenia. This review introduces
      pathogenesis of cognitive impairment in schizophrenia, mechanisms of blonanserin
      and lurasidone in the improvement of cognitive impairment and progress in their
      clinical application for schizophrenia. We hope that this review could guide
      clinical use of antipsychotics and provide new directions for future studies.

PMID- 28490710
TI  - [Small fugal enteritis manifestation with intestinal obstruction and
      hematochezia: a case report].
AB  - Fungal enteritis was rarely reported. A case of fungal enteritis manifestation
      with jejunum multiple ulcers and obstruction was treated by Department of
      Gastroenterology, Third Xiangya Hospital, Central South University. After
      antifungal treatment, the clinical symptoms were relieved, and the ulcers in
      jejunal and upper gastrointestinal tract were healed completely. Clinical
      manifestation for small fungal enteritis is special, and the small intestine
      ulcer is easily to be misdiagnosed. It is helpful to prevent the misdiagnose for
      small fungal enteritis if we can tell the clinical features for this disease.

PMID- 28490711
TI  - Purification, Crystallization and X-ray Diffraction Study of the C-terminal
      Domain of Human Herpesvirus 6A Immediate Early Protein 2.
AB  - Human herpesvirus 6A (HHV-6A) starts its replication cycle following the action
      of immediate early proteins that transactivate viral promoters. Immediate early
      protein 2 (IE2) of HHV-6A is a 1500 amino acid polypeptide with a C-terminal
      region that is conserved among beta-herpesvirus subfamily members. In this study,
      a structural domain in the homologous C-terminal region was subjected to
      secondary structure prediction, and residues 1324-1500 were subsequently
      designated as the C-terminal domain of IE2 (IE2-CTD). The gene fragment encoding
      IE2-CTD was inserted into an E. coli expression vector and expressed as a fusion
      protein with maltose binding protein (MBP) at the N-terminus. IE2-CTD has a
      theoretical isoelectric point (pI) of 9.29, and strong cation exchange column
      chromatography was effective for purification. Needle-shaped crystals of IE2-CTD
      were obtained using the sitting-drop vapour diffusion method, and larger
      selenomethionine-labelled crystals of space group P21 diffracted X-rays to 2.5 A
      resolution using synchrotron radiation. Data were collected at the selenium
      absorption peak wavelength for experimental phasing by the single anomalous
      dispersion method. The resulting electron density map clearly shows the protein
      backbone, and full structural determination and refinement are in progress.

PMID- 28490712
TI  - Application of Physiologically-Based Pharmacokinetic Modeling for the Prediction
      of Tofacitinib Exposure in Japanese.
AB  - Tofacitinib (3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4
      yl)amino]piperidin-1-yl]-3 -oxopropanenitrile) is an oral Janus kinase inhibitor
      that is approved in countries including Japan and the United States for the
      treatment of rheumatoid arthritis, and is being developed across the globe for
      the treatment of inflammatory diseases. In the present study, a physiologically
      based pharmacokinetic model was applied to compare the pharmacokinetics of
      tofacitinib in Japanese and Caucasians to assess the potential impact of
      ethnicity on the dosing regimen in the two populations. Simulated plasma
      concentration profiles and pharmacokinetic parameters, i.e. maximum concentration
      and area under plasma concentration-time curve, in Japanese and Caucasian
      populations after single or multiple doses of 1 to 30 mg tofacitinib were in
      agreement with clinically observed data. The similarity in simulated exposure
      between Japanese and Caucasian populations supports the currently approved dosing
      regimen in Japan and the United States, where there is no recommendation for dose
      adjustment according to race. Simulated results for single (1 to 100 mg) or
      multiple doses (5 mg twice daily) of tofacitinib in extensive and poor
      metabolizers of CYP2C19, an enzyme which has been shown to contribute in part to
      tofacitinib elimination and is known to exhibit higher frequency in Japanese
      compared to Caucasians, were also in support of no recommendation for dose
      adjustment in CYP2C19 poor metabolizers. This study demonstrated a successful
      application of physiologically-based pharmacokinetic modeling in evaluating
      ethnic sensitivity in pharmacokinetics at early stages of development, presenting
      its potential value as an efficient and scientific method for optimal dose
      setting in the Japanese population.

PMID- 28490713
TI  - Phospholipase D is Dispensable for Epidermal Growth Factor-Induced Chemotaxis.
AB  - alpha-Synuclein (alpha-Syn) is implicated in several neurodegenerative disorders,
      including Parkinson's disease, known collectively as the synucleinopathies. alpha
      Syn is known to be secreted from the cells and may contribute to the progression
      of the disease. Although extracellular alpha-Syn is shown to impair platelet
      derived growth factor-induced chemotaxis, molecular mechanism of alpha-Syn
      induced motility failure remains elusive. Here we have aimed at phospholipase D
      (PLD) as a potential target for alpha-Syn and examined the involvement of this
      enzyme in alpha-Syn action. Indeed, extracellular alpha-Syn caused inhibition of
      agonist-induced PLD activation. However, inhibition of hydrolytic activity of PLD
      by 1-butanol treatment showed little or no effect on agonist-induced chemotaxis.
      These results suggest that some signaling pathways other than PLD may be involved
      in alpha-Syn-induced inhibition of chemotaxis.

PMID- 28490714
TI  - The seroprevalence of Bartonella henselae in healthy adults in Korea.
AB  - BACKGROUND/AIMS: Cat-scratch disease (CSD), caused by Bartonella henselae is one
      of the most common zoonosis. However, only several cases of B. henselae infection
      have been reported in Korea. This study investigated the seroprevalence of B.
      henselae in healthy adults and related risk factors. METHODS: Serum samples from
      300 healthy participants were analyzed using an immunoglobulin G immunof
      luorescence assay (IFA) for B. henselae isolated in Korea. Surveys on the risk
      factors for B. henselae infection were conducted simultaneously. RESULTS: Of the
      participants, 47.7% and 15.0% raised dogs and cats, respectively. The overall
      seroprevalence of B. henselae was 15.0% (IFA titer >= 1:64). Participants who had
      raised cats showed 22.2% seropositivity against B. henselae, and those with no
      experience with cats showed 13.7% seroprevalence (p = 0.17). Participants who had
      cats as pets or been scratched by cats, showed 9.8% seropositivity against B.
      henselae (IFA titer >= 1:256). However, those who had not raised or been
      scratched by a cat showed 2.0% seropositivity (p = 0.015). CONCLUSIONS: In Korea,
      the seroprevalence of B. henselae is higher than expected, suggesting that
      Bartonella infection due to B. henselae is not uncommon. Cats are proposed to
      play a more important role than dogs in transmission of CSD.

PMID- 28490715
TI  - Approach to cytomegalovirus infections in patients with ulcerative colitis.
AB  - Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative
      colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or
      administration of immunosuppressants. The question of whether CMV is an active
      pathogen or 'an innocent bystander' in the exacerbation of UC remains
      controversial. Patients with UC exacerbated by reactivated CMV experience worse
      prognoses than those without CMV reactivation and antiviral therapy significantly
      reduces the need for colectomy in patients with severe UC and high-grade CMV
      infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV
      status of patients on immunosuppressants, particularly those with steroid
      refractory or -dependent UC, should be tested. When CMV is detected, be performed
      based on should adequate treatment the extent of the viral load and the presence
      of certain clinical features including a large ulcer. Anti-tumor necrosis factor
      agents may be useful for treating CMV colitis complicating UC.

PMID- 28490716
TI  - Comment on "Hypogonadotrophic hypogonadism due to a mutation in the luteinizing
      hormone beta-subunit gene".

PMID- 28490717
TI  - Erratum: Two-year clinical outcomes in stable angina and acute coronary syndrome
      after percutaneous coronary intervention of left main coronary artery disease.
AB  - [This corrects the article on p. 1084 in vol. 31, PMID: 27756119.].

PMID- 28490718
TI  - Comment on "New therapeutic agents in diabetic nephropathy".

PMID- 28490719
TI  - Realities of KRAS-mutated non-small cell lung cancer.

PMID- 28490720
TI  - Oxidative stress: link between hypertension and diabetes.

PMID- 28490721
TI  - Response to comment on "New therapeutic agents in diabetic nephropathy".

PMID- 28490722
TI  - Response to comment on "Hypogonadotrophic hypogonadism due to a mutation in the
      luteinizing hormone beta-subunit gene".

PMID- 28490723
TI  - Incidence and clinical characteristics of gastroenteropancreatic neuroendocrine
      tumor in Korea: a single-center experience.
AB  - BACKGROUND/AIMS: Neuroendocrine tumors (NETs) may originate from heterogeneous
      neuroendocrine cells. The incidence is increasing worldwide, and World Health
      Organization (WHO) updated its classification in 2010. We investigated clinical
      characteristics of gastroenteropancreatic NETs in a single center. METHODS:
      Clinicopathologic characteristics of patients with pathologically confirmed
      gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August
      2011 were retrospectively analyzed. The grade and stage were determined according
      to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th
      ed., 2010) of American Joint Committee on Cancer. RESULTS: One hundred and twenty
      five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients
      who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a
      functional NET. The rectum (n = 99, 79.8%) was most common primary site and found
      in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8%
      stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7%
      grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic
      grade (Spearman's rank correlation coefficient, 0.644). CONCLUSIONS: Wide range
      of clinicopathological features of Korean gastroenteropancreatic NETs were
      demonstrated using WHO 2010 classification. Rectal NET was most frequent and
      found in early stage.

PMID- 28490724
TI  - Infection in systemic lupus erythematosus, similarities, and differences with
      lupus flare.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse
      manifestations, and its pathogenesis is unclear and complicated. Infection and
      SLE are similar in that they both cause inf lammatory reactions in the immune
      system; however, one functions to protect the body, whereas the other is
      activated to damage the body. Infection is known as one of the common trigger
      factors for SLE; there are a number of reports on infectious agents that provoke
      autoimmune response. Several viruses, bacteria, and protozoa were revealed to
      cause immune dysfunction by molecular mimicry, epitope spreading, and bystander
      activation. In contrast, certain pathogens were revealed to protect from immune
      dysregulation. Infection can be threatening to patients with SLE who have a
      compromised immune system, and it is regarded as one of the common causes of
      mortality in SLE. A clinical distinction between infection and lupus f lare up is
      required when patients with SLE present fevers. With a close-up assessment of
      symptoms and physical examination, C-reactive protein and disease activity
      markers play a major role in differentiating the different disease conditions.
      Vaccination is necessary because protection against infection is important in
      patients with SLE.

PMID- 28490725
TI  - Effects of valsartan and amlodipine on oxidative stress in type 2 diabetic
      patients with hypertension: a randomized, multicenter study.
AB  - BACKGROUND/AIMS: Oxidative stress plays an important role in the pathogenesis and
      progression of diabetic complications and antagonists of renin-angiotensin system
      and amlodipine have been reported previously to reduce oxidative stress. In this
      study, we compared the changes in oxidative stress markers after valsartan and
      amlodipine treatment in type 2 diabetic patients with hypertension and compared
      the changes in metabolic parameters. METHODS: Type 2 diabetic subjects with
      hypertension 30 to 80 years of age who were not taking antihypertensive drugs
      were randomized into either valsartan (n = 33) or amlodipine (n = 35) groups and
      treated for 24 weeks. We measured serum nitrotyrosine levels as an oxidative
      stress marker. Metabolic parameters including serum glucose, insulin, lipid
      profile, and urine albumin and creatinine were also measured. RESULTS: After 24
      weeks of valsartan or amlodipine treatment, systolic and diastolic blood pressure
      decreased, with no significant difference between the groups. Both groups showed
      a decrease in serum nitrotyrosine (7.74 +/- 7.30 nmol/L vs. 3.95 +/- 4.07 nmol/L
      in the valsartan group and 8.37 +/- 8.75 nmol/L vs. 2.68 +/- 2.23 nmol/L in the
      amlodipine group) with no significant difference between the groups. Other
      parameters including glucose, lipid profile, albumin-to-creatinine ratio, and
      homeostasis model assessment of insulin resistance showed no significant
      differences before and after treatment in either group. CONCLUSIONS: Valsartan
      and amlodipine reduced the oxidative stress marker in type 2 diabetic patients
      with hypertension.

PMID- 28490726
TI  - Plasma Long Noncoding RNA Urothelial Carcinoma Associated 1 Predicts Poor
      Prognosis in Chronic Heart Failure Patients.
AB  - BACKGROUND Chronic heart failure (CHF) is a leading cause of death worldwide. A
      long noncoding RNA (lncRNA) named urothelial carcinoma associated 1 (UCA1) is
      important in multiple diseases. However, the role of UCA1 in CHF is still
      unknown. Our study investigated whether UCA1 could be applied as an ideal marker
      to diagnose and evaluate prognosis in CHF. MATERIAL AND METHODS Total plasma RNA
      was extracted from 67 CHF patients and 67 controls. Quantitative real-time
      polymerase chain reaction was used to determine the plasma level of UCA1.
      Correlations between UCA1 and clinical parameters were analyzed by Pearson
      correlation. Receiver operating characteristic curves (ROC) were obtained to
      analyze the predictive power of UCA1 and BNP for CHF. Kaplan-Meier survival
      curves were used to evaluate prognosis of CHF within 1 year. RESULTS There was no
      significant difference in elementary data between CHF and controls. Plasma UCA1
      was much higher in CHF patients compared with controls. Plasma UCA1 was
      positively and negatively correlated with brain natriuretic peptide (BNP) and
      left ventricle ejection fraction (LVEF), respectively. Plasma UCA1 diagnosed CHF
      with a diagnostic power of 0.89 and a sensitivity and specificity of 100% [95% CI
      (0.9464-1)] and 76.12% [95%CI (0.6414-0.8569)] (P<0.05), respectively. CHF
      patients with higher plasma UCA1 had a lower survival rate than those with a
      lower level, and survival rate predicted by UCA1 had a similar tendency with BNP.
      However, there was no significant difference between these 2 markers in
      predicting the prognosis of CHF (P>0.05). CONCLUSIONS Plasma UCA1 might be an
      excellent indicator to diagnose CHF and it might predict poor outcomes of CHF.

PMID- 28490727
TI  - Syringocystadenoma Papilliferum of the External Auditory Canal.
AB  - BACKGROUND Ceruminous glands are modified apocrine glands, situated in the
      external auditory canal, that, together with sebaceous glands, produce cerumen,
      better known as ear wax. The neoplastic transformation of these structures is
      very rare and there have been few cases reported in the literature. CASE REPORT
      Syringocystadenoma papilliferum is one of the rarest tumors among benign tumors
      arising from the ceruminous glands. We here report the case of a 72-year-old man
      with a lesion histologically documented as a syringocystadenoma papilliferum and
      we review the literature, focusing our attention on clinical features and
      treatment options of benign glandular tumors arising from the external auditory
      canal. CONCLUSIONS Syringocystadenoma papilliferum is a rare benign tumor of the
      ceruminous glands of the external ear canal. Excision biopsy is mandatory for the
      diagnosis and is the best treatment.

PMID- 28490728
TI  - Bright nanoscale source of deterministic entangled photon pairs violating Bell's
      inequality.
AB  - Global, secure quantum channels will require efficient distribution of entangled
      photons. Long distance, low-loss interconnects can only be realized using photons
      as quantum information carriers. However, a quantum light source combining both
      high qubit fidelity and on-demand bright emission has proven elusive. Here, we
      show a bright photonic nanostructure generating polarization-entangled photon
      pairs that strongly violates Bell's inequality. A highly symmetric InAsP quantum
      dot generating entangled photons is encapsulated in a tapered nanowire waveguide
      to ensure directional emission and efficient light extraction. We collect ~200
      kHz entangled photon pairs at the first lens under 80 MHz pulsed excitation,
      which is a 20 times enhancement as compared to a bare quantum dot without a
      photonic nanostructure. The performed Bell test using the Clauser-Horne-Shimony
      Holt inequality reveals a clear violation (S CHSH > 2) by up to 9.3 standard
      deviations. By using a novel quasi-resonant excitation scheme at the wurtzite InP
      nanowire resonance to reduce multi-photon emission, the entanglement fidelity (F
      = 0.817 +/- 0.002) is further enhanced without temporal post-selection, allowing
      for the violation of Bell's inequality in the rectilinear-circular basis by 25
      standard deviations. Our results on nanowire-based quantum light sources
      highlight their potential application in secure data communication utilizing
      measurement-device-independent quantum key distribution and quantum repeater
      protocols.

PMID- 28490729
TI  - A comparative multi-parametric in vitro model identifies the power of test
      conditions to predict the fibrotic tendency of a biomaterial.
AB  - Despite growing effort to advance materials towards a low fibrotic progression,
      all implants elicit adverse tissue responses. Pre-clinical biomaterial assessment
      relies on animals testing, which can be complemented by in vitro tests to address
      the Russell and Burch's 3R aspect of reducing animal burden. However, a poor
      correlation between in vitro and in vivo biomaterial assessments confirms a need
      for suitable in vitro biomaterial tests. The aim of the study was to identify a
      test setting, which is predictive and might be time- and cost-efficient. We
      demonstrated how sensitive in vitro biomaterial assessment based on human primary
      macrophages depends on test conditions. Moreover, possible clinical scenarios
      such as lipopolysaccharide contamination, contact to autologous blood plasma, and
      presence of IL-4 in an immune niche influence the outcome of a biomaterial
      ranking. Nevertheless, by using glass, titanium, polytetrafluorethylene,
      silicone, and polyethylene representing a specific material-induced fibrotic
      response and by comparison to literature data, we were able to identify a test
      condition that provides a high correlation to state-of-the-art in vivo studies.
      Most important, biomaterial ranking obtained under native plasma test conditions
      showed a high predictive accuracy compared to in vivo assessments, strengthening
      a biomimetic three-dimensional in vitro test platform.

PMID- 28490731
TI  - The intestinal tuft cell nanostructure in 3D.
AB  - Once referred to as "peculiar," tuft cells are enigmatic epithelial cells. Here,
      we reasoned that future functional studies could be derived from a complete
      account of the tuft cell ultrastructure. We identified and documented the
      volumetric ultrastructure at nanometer resolution (4-5 nm/pixel) of specific
      intestinal tuft cells. The techniques used were Serial Block-Face (SBF) and
      Automated Tape-collecting Ultra-Microtome (ATUM) Scanning Electron Microscopy
      (SEM). Our results exposed a short (~15 um) basal cytoplasmic process devoid of
      secretory vesicles. Volume rendering of serial sections unveiled several thin
      cytospinules (~1 um). These cytospinules project from the tuft cell into the
      nuclei of neighboring epithelial cells. Volume rendering also revealed within the
      tuft cell an elegant network of interconnected tubules. The network forms a
      passage from the base of the microvilli to the rough endoplasmic reticulum. Based
      on their location and microanatomy, the tuft cells' cytospinules, and tubular
      network, might facilitate the exchange of molecular cargo with nuclei of
      neighboring cells, and the gut lumen.

PMID- 28490730
TI  - Multi-pass transmission electron microscopy.
AB  - Feynman once asked physicists to build better electron microscopes to be able to
      watch biology at work. While electron microscopes can now provide atomic
      resolution, electron beam induced specimen damage precludes high resolution
      imaging of sensitive materials, such as single proteins or polymers. Here, we use
      simulations to show that an electron microscope based on a multi-pass measurement
      protocol enables imaging of single proteins, without averaging structures over
      multiple images. While we demonstrate the method for particular imaging targets,
      the approach is broadly applicable and is expected to improve resolution and
      sensitivity for a range of electron microscopy imaging modalities, including, for
      example, scanning and spectroscopic techniques. The approach implements a quantum
      mechanically optimal strategy which under idealized conditions can be considered
      interaction-free.

PMID- 28490732
TI  - Confocal imaging of single BaTiO3 nanoparticles by two-photon photothermal
      microscopy.
AB  - We report on the development of a nonlinear optical microscopic technique based
      on two-photon absorption induced photothermal effect capable of detecting
      individual nonfluorescent nanoparticles with high sensitivity. The method which
      is inherently confocal makes use of near infrared excitation at high repetition
      rates and would be of interest in deep tissue imaging. We demonstrate the
      applicability of the technique by imaging single BaTiO3 nanoparticles, a
      potential biomolecular label having high photostability, in a scattering
      environment at fast time scales with a pixel dwell time of 80 MUs.

PMID- 28490733
TI  - Pharmacometabolomics for predicting variable busulfan exposure in paediatric
      haematopoietic stem cell transplantation patients.
AB  - Owing to its narrow therapeutic range and high pharmacokinetic variability,
      optimal dosing for busulfan is important to minimise overexposure-related
      systemic toxicity and underexposure-related graft failure. Using global
      metabolomics, we investigated biomarkers for predicting busulfan exposure. We
      analysed urine samples obtained before busulfan administration from 59 paediatric
      patients divided into 3 groups classified by area under the busulfan
      concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups. In the
      high-AUC group, deferoxamine metabolites were detected. Phenylacetylglutamine and
      two acylcarnitines were significantly lower in the high-AUC group than in the low
      AUC group. Deferoxamine, an iron-chelating agent that lowers serum ferritin
      levels, was detected in the high-AUC group, indicating that those patients had
      high ferritin levels. Therefore, in a retrospective study of 130 paediatric
      patients, we confirmed our hypothesis that busulfan clearance (dose/AUC) and
      serum ferritin level has a negative correlation (r = -0.205, P = 0.019).
      Ferritin, acylcarnitine, and phenylacetylglutamine are associated with liver
      damage, including free radical formation, deregulation of hepatic mitochondrial
      beta-oxidation, and hyperammonaemia. Our findings reveal potential biomarkers
      predictive of busulfan exposure and suggest that liver function may affect
      busulfan exposure.

PMID- 28490734
TI  - Identification and activation of TLR4-mediated signalling pathways by alginate
      derived guluronate oligosaccharide in RAW264.7 macrophages.
AB  - Alginate, a natural acidic polysaccharide extracted from marine brown seaweeds,
      is composed of different blocks of beta-(1, 4)-D-mannuronate (M) and its C-5
      epimer alpha-(1, 4)-L-guluronate (G). Alginate-derived guluronate oligosaccharide
      (GOS) readily activates macrophages. However, to understand its role in immune
      responses, further studies are needed to characterize GOS transport and
      signalling. Our results show that GOS is recognized by and upregulates Toll-like
      receptor 4 (TLR4) on RAW264.7 macrophages, followed by its endocytosis via TLR4.
      Increased expression of TLR4 and myeloid differentiation protein 2 (MD2) results
      in Akt phosphorylation and subsequent activation of both nuclear factor-kappaB
      (NF-kappaB) and mechanistic target of rapamycin (mTOR). Moreover, GOS stimulates
      mitogen-activated protein kinases (MAPKs); notably, c-Jun N-terminal kinase (JNK)
      phosphorylation depends on TLR4 initiation. All these events contribute to the
      production of inflammatory mediators, either together or separately. Our findings
      also reveal that GOS induces cytoskeleton remodelling in RAW264.7 cells and
      promotes macrophage proliferation in mice ascites, both of which improve innate
      immunity. Conclusively, our investigation demonstrates that GOS, which is
      dependent on TLR4, is taken up by macrophages and stimulates TLR4/Akt/NF-kappaB,
      TLR4/Akt/mTOR and MAPK signalling pathways and exerts impressive immuno
      stimulatory activity.

PMID- 28490735
TI  - Design, Synthesis and Biological Evaluation of novel Hedgehog Inhibitors for
      treating Pancreatic Cancer.
AB  - Hedgehog (Hh) pathway is involved in epithelial-mesenchymal transition (EMT) and
      cancer stem cell (CSC) maintenance resulting in tumor progression. GDC-0449, an
      inhibitor of Hh pathway component smoothened (Smo) has shown promise in the
      treatment of various cancers including pancreatic cancer. However, the emergence
      of resistance during GDC-0449 treatment with numerous side effects limits its
      use. Therefore, here we report the design, synthesis and evaluation of novel GDC
      0449 analogs using N-[3-(2-pyridinyl) phenyl] benzamide scaffold. Cell-based
      screening followed by molecular simulation revealed 2-chloro-N 1-[4-chloro-3-(2
      pyridinyl)phenyl]-N 4,N 4-bis(2-pyridinylmethyl)-1,4-benzenedicarboxamide (MDB5)
      as most potent analog, binding with an extra interactions in seven-transmembrane
      (7-TM) domain of Smo due to an additional 2-pyridylmethyl group than GDC-0449.
      Moreover, MDB5 was more efficient in inhibiting Hh pathway components as measured
      by Gli-1 and Shh at transcriptional and translational levels. Additionally, a
      significant reduction of ALDH1, CD44 and Oct-3/4, key markers of pancreatic CSC
      was observed when MIA PaCa-2 cells were treated with MDB5 compared to GDC-0449.
      In a pancreatic tumor mouse model, MDB5 containing nanoparticles treated group
      showed significant inhibition of tumor growth without loss in body weight. These
      evidence highlight the enhanced Hh pathway inhibition and anticancer properties
      of MDB5 leaving a platform for mono and/or combination therapy.

PMID- 28490736
TI  - Extracellular Vesicles Carry HIV Env and Facilitate Hiv Infection of Human
      Lymphoid Tissue.
AB  - Cells productively infected with HIV-1 release virions along with extracellular
      vesicles (EVs) whose biogenesis, size, and physical properties resemble those of
      retroviruses. Here, we found that a significant number of EVs (exosomes) released
      by HIV-1 infected cells carry gp120 (Env), a viral protein that mediates virus
      attachment and fusion to target cells, and also facilitates HIV infection in
      various indirect ways. Depletion of viral preparations of EVs, in particular of
      those that carry gp120, decreases viral infection of human lymphoid tissue ex
      vivo. Thus, EVs that carry Env identified in our work seem to facilitate HIV
      infection and therefore may constitute a new therapeutic target for antiviral
      strategy.

PMID- 28490737
TI  - Intradermal administration of IL-33 induces allergic airway inflammation.
AB  - Approximately half of all atopic dermatitis (AD) patients subsequently develop
      asthma, particularly those with severe AD. This association, suggesting a role
      for AD as an entry point for subsequent allergic disease, is a phenomenon known
      as the "atopic march". While the underlying cause of the atopic march remains
      unknown, recent evidence suggests that epithelial cell (EC)-derived cytokines
      play a major role. We showed that mice exposed to antigen through the skin, in
      the presence of IL-33, developed antigen-specific airway inflammation when later
      challenged in the lung. IL-33 signaling was dispensable during effector/challenge
      phase. These data reveal critical roles for IL-33 in the "atopic march" and will
      offer a new therapeutic target in the treatment and prevention of allergic
      asthma.

PMID- 28490738
TI  - Model-guided control of hippocampal discharges by local direct current
      stimulation.
AB  - Neurostimulation is an emerging treatment for drug-resistant epilepsies when
      surgery is contraindicated. Recent clinical results demonstrate significant
      seizure frequency reduction in epileptic patients, however the mechanisms
      underlying this therapeutic effect are largely unknown. This study aimed at
      gaining insights into local direct current stimulation (LDCS) effects on
      hyperexcitable tissue, by i) analyzing the impact of electrical currents locally
      applied on epileptogenic brain regions, and ii) characterizing currents achieving
      an "anti-epileptic" effect (excitability reduction). First, a neural mass model
      of hippocampal circuits was extended to accurately reproduce the features of
      hippocampal paroxysmal discharges (HPD) observed in a mouse model of epilepsy.
      Second, model predictions regarding current intensity and stimulation polarity
      were confronted to in vivo mice recordings during LDCS (n = 8). The neural mass
      model was able to generate realistic hippocampal discharges. Simulation of LDCS
      in the model pointed at a significant decrease of simulated HPD (in duration and
      occurrence rate, not in amplitude) for cathodal stimulation, which was
      successfully verified experimentally in epileptic mice. Despite the simplicity of
      our stimulation protocol, these results contribute to a better understanding of
      clinical benefits observed in epileptic patients with implanted neurostimulators.
      Our results also provide further support for model-guided design of
      neuromodulation therapy.

PMID- 28490739
TI  - Honokiol inhibits ultraviolet radiation-induced immunosuppression through
      inhibition of ultraviolet-induced inflammation and DNA hypermethylation in mouse
      skin.
AB  - Ultraviolet (UV) radiation exposure induces immunosuppression, which contributes
      to the development of cutaneous malignancies. We investigated the effects of
      honokiol, a phytochemical found in plants of the genus Magnolia, on UVB-induced
      immunosuppression using contact hypersensitivity (CHS) as a model in C3H/HeN
      mice. Topical application of honokiol (0.5 and 1.0 mg/cm2 skin area) had a
      significant preventive effect on UVB-induced suppression of the CHS response. The
      inflammatory mediators, COX-2 and PGE2, played a key role in this effect, as
      indicated by honokiol inhibition of cyclooxygenase-2 (COX-2) expression and PGE2
      production in the UVB-exposed skin. Honokiol application also inhibited UVB
      induced DNA hypermethylation and its elevation of the levels of TET enzyme, which
      is responsible for DNA demethylation in UVB-exposed skin. This was consistent
      with the restoration of the CHS response in mice treated with the DNA
      demethylating agent, 5-aza-2'-deoxycytidine, after UVB exposure. There was no
      significant difference in the levels of inhibition of UVB-induced
      immunosuppression amongst mice that were treated topically with available anti
      cancer drugs (imiquimod and 5-fluorouracil). This study is the first to show that
      honokiol has the ability to inhibit UVB-induced immunosuppression in preclinical
      model and, thus, has potential for use as a chemopreventive strategy for UVB
      radiation-induced malignancies.

PMID- 28490740
TI  - Presence of heterocyclic amine carcinogens in home-cooked and fast-food camel
      meat burgers commonly consumed in Saudi Arabia.
AB  - Heterocyclic amines (HCAs) are formed by cooking protein-rich foods, for
      instance, meat and fish, and are listed as possible human carcinogens. In the
      present study, the presence of five potential HCAs (IQ, MeIQ, MeIQx, 4,8-DiMeIQx,
      and PhIP) in cooked camel meat burgers was analyzed for the first time. The
      analysis was performed in home-cooked and fast-food burger samples containing
      food additives. The applied cooking technique for the home-cooked samples was pan
      frying for a controlled cooking time and temperature. In the control cooked meat
      samples (samples that contained no food additives), the concentrations of MeIQx,
      4,8-DiMeIQx, and PhIP ranged from 2.47 ng/g to 4.89 ng/g, whereas IQ and MeIQ
      were found to be below the limit of quantification. The concentrations contents
      of MeIQx, 4,8-DiMeIQx, and PhIP in the home-cooked and fast-food samples ranged
      from 1.52 ng/g to 2.13 ng/g and 1.85 ng/g to 3.46 ng/g, respectively. IQ and MeIQ
      were not detected in either type of sample. In comparison to the control samples,
      the home-cooked and fast-food samples produced lower levels of HCAs. Such
      observations could result from the existence of antioxidants in incorporated food
      additives, which induce pro-oxidative effects with the successive formation
      and/or scavenging of free radicals.

PMID- 28490741
TI  - Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence
      from comprehensive miRNA expression profiling analysis and clinical validation.
AB  - Pancreatic cancer (PC) is a highly fatal disease worldwide and is often
      misdiagnosed in its early stages. The exploration of novel non-invasive
      biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in
      body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this
      study, we first conducted comprehensive robust rank aggregation (RRA) analysis
      based on 21 published miRome profiling studies. We statistically identified and
      clinically validated a miRNA expression pattern in PC patients. These miRNAs
      consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and
      hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and
      hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed
      miRNAs in the serum of PC patients. Our validation test further suggested a
      relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC,
      with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta
      analysis based on 9 studies also revealed favorable sensitivity and specificity
      of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and
      specificity were 0.76 and 0.74, respectively), which was consistent with our
      findings. Taken together, as one of the most aberrantly expressed miRNAs in PC,
      circulating hsa-miR-21-5p might be a promising serum biomarker in patients with
      PC.

PMID- 28490742
TI  - Fabrication and Wettability Study of WO3 Coated Photocatalytic Membrane for Oil
      Water Separation: A Comparative Study with ZnO Coated Membrane.
AB  - Superhydrophilic and underwater superoleophobic surfaces were fabricated by
      facile spray coating of nanostructured WO3 on stainless steel meshes and compared
      its performance in oil-water separation with ZnO coated meshes. The gravity
      driven oil-water separation system was designed using these surfaces as the
      separation media and it was noticed that WO3 coated stainless steel mesh showed
      high separation efficiency (99%), with pore size as high as 150 um, whereas ZnO
      coated surfaces failed in the process of oil-water separation when the pore
      exceeded 50 um size. Since, nanostructured WO3 is a well known catalyst, the
      simultaneous photocatalytic degradation of organic pollutants present in the
      separated water from the oil water separation process were tested using WO3
      coated surfaces under UV radiation and the efficiency of this degradation was
      found to be quite significant. These results assure that with little
      improvisation on the oil water separation system, these surfaces can be made
      multifunctional to work simultaneously for oil-water separation and
      demineralization of organic pollutants from the separated water. Fabrication of
      the separating surface, their morphological characteristics, wettability, oil
      water separation efficiency and photo-catalytic degradation efficiency are
      enunciated.

PMID- 28490743
TI  - Allelic imbalance of somatic mutations in cancer genomes and transcriptomes.
AB  - Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation
      abundance between the genome and transcriptome, but there is not yet a systematic
      understanding of AI. In this study, we performed large-scale DNA and RNA AI
      analyses of >100,000 somatic mutations in >2,000 cancer specimens across five
      tumor types using the exome and transcriptome sequencing data of the Cancer
      Genome Atlas consortium. First, AI analysis of nonsense mutations and frameshift
      indels revealed that nonsense-mediated decay is typical in cancer genomes, and we
      identified the relationship between the extent of AI and the location of
      mutations in addition to the well-recognized 50-nt rules. Second, the AI with
      splice site mutations may reflect the extent of intron retention and is
      frequently observed in known tumor suppressor genes. For missense mutations, we
      observed that mutations frequently subject to AI are enriched to genes related to
      cancer, especially those of apoptosis and the extracellular matrix, and C:G > A:T
      transversions. Our results suggest that mutations in known cancer-related genes
      and their transcripts are subjected to different levels of transcriptional or
      posttranscriptional regulation compared to wildtype alleles and may add an
      additional regulatory layer to the functions of cancer-relevant genes.

PMID- 28490744
TI  - Precision Radiology: Predicting longevity using feature engineering and deep
      learning methods in a radiomics framework.
AB  - Precision medicine approaches rely on obtaining precise knowledge of the true
      state of health of an individual patient, which results from a combination of
      their genetic risks and environmental exposures. This approach is currently
      limited by the lack of effective and efficient non-invasive medical tests to
      define the full range of phenotypic variation associated with individual health.
      Such knowledge is critical for improved early intervention, for better treatment
      decisions, and for ameliorating the steadily worsening epidemic of chronic
      disease. We present proof-of-concept experiments to demonstrate how routinely
      acquired cross-sectional CT imaging may be used to predict patient longevity as a
      proxy for overall individual health and disease status using computer image
      analysis techniques. Despite the limitations of a modest dataset and the use of
      off-the-shelf machine learning methods, our results are comparable to previous
      'manual' clinical methods for longevity prediction. This work demonstrates that
      radiomics techniques can be used to extract biomarkers relevant to one of the
      most widely used outcomes in epidemiological and clinical research - mortality,
      and that deep learning with convolutional neural networks can be usefully applied
      to radiomics research. Computer image analysis applied to routinely collected
      medical images offers substantial potential to enhance precision medicine
      initiatives.

PMID- 28490745
TI  - A nanofabricated, monolithic, path-separated electron interferometer.
AB  - Progress in nanofabrication technology has enabled the development of numerous
      electron optic elements for enhancing image contrast and manipulating electron
      wave functions. Here, we describe a modular, self-aligned, amplitude-division
      electron interferometer in a conventional transmission electron microscope. The
      interferometer consists of two 45-nm-thick silicon layers separated by 20 MUm.
      This interferometer is fabricated from a single-crystal silicon cantilever on a
      transmission electron microscope grid by gallium focused-ion-beam milling. Using
      this interferometer, we obtain interference fringes in a Mach-Zehnder geometry in
      an unmodified 200 kV transmission electron microscope. The fringes have a period
      of 0.32 nm, which corresponds to the [111] lattice planes of silicon, and a
      maximum contrast of 15%. We use convergent-beam electron diffraction to quantify
      grating alignment and coherence. This design can potentially be scaled to
      millimeter-scale, and used in electron holography. It could also be applied to
      perform fundamental physics experiments, such as interaction-free measurement
      with electrons.

PMID- 28490746
TI  - Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of
      mitochondrial substrates.
AB  - Abnormal mitochondrial function has been found in patients with frontotemporal
      dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene
      (also known as SQSTM1) which encodes the p62 protein have been reported in both
      disorders supporting the idea of an ALS/FTD continuum. In this work the role of
      p62 in energy metabolism was studied in fibroblasts from FTD patients carrying
      two independent pathogenic mutations in the p62 gene, and in a p62-knock-down
      (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). We found that p62
      deficiency is associated with inhibited complex I mitochondrial respiration due
      to lack of NADH for the electron transport chain. This deficiency was also
      associated with increased levels of NADPH reflecting a higher activation of
      pentose phosphate pathway as this is accompanied with higher cytosolic reduced
      glutathione (GSH) levels. Complex I inhibition resulted in lower mitochondrial
      membrane potential and higher cytosolic ROS production. Pharmacological
      activation of transcription factor Nrf2 increased mitochondrial NADH levels and
      restored mitochondrial membrane potential in p62-deficient cells. Our results
      suggest that the phenotype is caused by a loss-of-function effect, because
      similar alterations were found both in the mutant fibroblasts and the p62 KD
      model. These findings highlight the implication of energy metabolism in
      pathophysiological events associated with p62 deficiency.

PMID- 28490747
TI  - Structural Basis for Importin-alpha Binding of the Human Immunodeficiency Virus
      Tat.
AB  - HIV-1 has caused 35 million deaths globally, and approximately the same number is
      currently living with HIV-1. The trans-activator of transcription (Tat) protein
      of HIV-1 plays an important regulatory function in the virus life cycle,
      responsible for regulating the reverse transcription of the viral genome RNA. Tat
      is found in the nucleus of infected cells, but can also invade uninfected
      neighbouring cells. Regions within Tat responsible for these cellular
      localisations are overlapping and include a nuclear localisation signal (NLS)
      spanning 48GRKKRR, and a cell penetrating peptide (CPP) signal spanning
      48GRKKRRQRRRAPQN. However, the mechanism by which this NLS/CPP region mediates
      interaction with the nuclear import receptors remains to be resolved
      structurally. Here, we establish that the HIV-1 Tat:NLS/CPP is able to form a
      stable and direct interaction with the classical nuclear import receptor importin
      alpha and using x-ray crystallography, we have determined the molecular interface
      and binding determinants to a resolution of 2.0 A. We show for the first time
      that the interface is the same as host factors such as Ku70 and Ku80, rather than
      other virus proteins such as Ebola VP24 that bind on the outer surface of
      importin-alpha.

PMID- 28490748
TI  - Nuclear DNA markers for identification of Beluga and Sterlet sturgeons and their
      interspecific Bester hybrid.
AB  - Sturgeons (Acipenseriformes) are among the most endangered species in the world
      due to fragmentation and destruction of their natural habitats and to
      overexploitation, mainly for highly priced caviar. This has led to the
      development of sturgeon culture, originally for reintroduction, but more recently
      for caviar production. In both cases, accurate species identification is
      essential. We report a new tool for accurate identification of Huso huso and
      Acipenser ruthenus based on nuclear DNA markers. We employed ddRAD sequencing to
      identify species-specific nucleotide variants, which served as specific binding
      sites for diagnostic primers. The primers allowed identification of Huso huso and
      Acipenser ruthenus as well as their discrimination from A. baerii, A. schrenckii,
      A. gueldenstaedtii, A. stellatus, A. persicus, A. mikadoi, A. transmontanus, and
      H. dauricus and identification of A. ruthenus and H. huso hybrids with these
      species, except hybrid between A. ruthenus and A. stellatus. The species-specific
      primers also allowed identification of bester (H. huso * A. ruthenus), the most
      commercially exploited sturgeon hybrid. The tool, based on simple PCR and gel
      electrophoresis, is rapid, inexpensive, and reproducible. It will contribute to
      conservation of remaining wild populations of A. ruthenus and H. huso, as well as
      to traceability of their products.

PMID- 28490749
TI  - Characterization of Product and Potential Mechanism of Cr(VI) Reduction by
      Anaerobic Activated Sludge in a Sequencing Batch Reactor.
AB  - Bioremediation of Cr(VI) and nitrate is considered as a promising and cost
      effective alternative to chemical and physical methods. However, organo-Cr(III)
      complexes in effluent generally causes environmental concerns due to second
      pollution. Here, Cr(VI) reduction and immobilization efficiencies of anaerobic
      activated sludge were investigated. Anaerobic activated sludge showed strong
      reduction ability of Cr(VI) and possessed a great potential of Cr(III)
      immobilization. Almost 100.0 mg l-1 Cr(VI) could be completely reduced and
      immobilized by anaerobic activated sludge in a sequencing batch reactor in 24 h.
      And most generated Cr(III) was accumulated outside of sludge cells. Extracellular
      polymeric substances (EPS) could bind to Cr(VI) and form EPS-Cr(VI) interaction
      to reduce the toxic effect of Cr(VI) and promote the Cr(VI) reduction. Protein
      like and humic-like substances were responsible for binding with Cr(VI),
      meanwhile the process was a thermodynamically favorable binding reaction. Then
      Cr(VI) was reduced to Cr(III) by membrane-associated chromate reductase of
      sludge. Eventually, the generated Cr(III) might exist as poly-nuclear Cr(III)
      complexes adhered to sludge surfaces.

PMID- 28490750
TI  - DV21 decreases excitability of cortical pyramidal neurons and acts in epilepsy.
AB  - Epilepsy is one of the most common neurological disorders and the administration
      of antiepileptic drugs (AEDs) is the most common treatment. Although there are
      more than 15 AEDs available, a third of epilepsy patients remain refractory to
      available drugs, so novel effective drugs are needed. Here, we found that DV21,
      which is a natural triterpenoid compound extracted from plants of the
      Asclepiadaceae family, significantly decreased the incidence and stages of
      seizures in three classical drug-induced acute seizure models in C57BL/6 mice.
      Furthermore, we also found that the antiepileptic effect of DV21 might be partly
      mediated through reducing the excitability of cortical pyramidal neurons by
      increasing M current, which are low-threshold non-inactivating voltage-gated
      potassium currents. Moreover, the application of XE991, an inhibitor of M
      current, could block most the antiepileptic effect of DV21. Taken together, our
      results indicated that DV21 might be a novel leading compound for the treatment
      of epilepsy.

PMID- 28490751
TI  - Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome.
AB  - Dravet syndrome, an epileptic encephalopathy affecting children, largely results
      from heterozygous loss-of-function mutations in the brain voltage-gated sodium
      channel gene SCN1A. Heterozygous Scn1a knockout (Scn1a +/-) mice recapitulate the
      severe epilepsy phenotype of Dravet syndrome and are an accepted animal model.
      Because clinical observations suggest conventional sodium channel blocking
      antiepileptic drugs may worsen the disease, we predicted the phenotype of Scn1a
      +/- mice would be exacerbated by GS967, a potent, unconventional sodium channel
      blocker. Unexpectedly, GS967 significantly improved survival of Scn1a +/- mice
      and suppressed spontaneous seizures. By contrast, lamotrigine exacerbated the
      seizure phenotype. Electrophysiological recordings of acutely dissociated neurons
      revealed that chronic GS967-treatment had no impact on evoked action potential
      firing frequency of interneurons, but did suppress aberrant spontaneous firing of
      pyramidal neurons and was associated with significantly lower sodium current
      density. Lamotrigine had no effects on neuronal excitability of either neuron
      subtype. Additionally, chronically GS967-treated Scn1a +/- mice exhibited
      normalized pyramidal neuron sodium current density and reduced hippocampal NaV1.6
      protein levels, whereas lamotrigine treatment had no effect on either pyramidal
      neuron sodium current or hippocampal NaV1.6 levels. Our findings demonstrate
      unexpected efficacy of a novel sodium channel blocker in Dravet syndrome and
      suggest a potential mechanism involving a secondary change in NaV1.6.

PMID- 28490752
TI  - Design, Fabrication and Characterization of Pressure-Responsive Films Based on
      The Orientation Dependence of Plasmonic Properties of Ag@Au Nanoplates.
AB  - A novel pressure-responsive polymer composite film was developed based on Ag@Au
      composite nanoplates (NPLs) and polyvinylpyrrolidone (PVP) by using Au
      nanoparticles as concentration reference. The orientation change of Ag@Au NPLs is
      impelled by the deformation of polymer matrix under pressure, resulting in its
      localized surface plasmon resonance (LSPR) intensity change of in-plane dipolar
      peak. The intensity ratio between plasmon peak of Au nanoparticles and in-plane
      dipolar peak of Ag@Au NPLs relies on the intensity and duration of pressure. By
      adjusting the viscosity of the polymer, the orientation change of LSPR may
      respond to a wide range of stresses. This pressure sensitive film can be utilized
      to record the magnitude and distribution of pressure between two contacting
      surfaces via optical information.

PMID- 28490753
TI  - WBC count predicts the risk of new-onset peripheral arterial disease in a Chinese
      community-based population.
AB  - This longitudinal cohort study investigated whether peripheral WBC counts could
      predict peripheral arterial disease (PAD) incidence after a 2.3-year follow-up in
      a Chinese community-based population without PAD at baseline. A total of 3555
      Chinese subjects without fever and PAD at baseline from an atherosclerosis cohort
      were included in our analysis. The ankle brachial index (ABI) was measured, and
      PAD was defined as an ABI <0.9. Multivariate regression models were used to
      evaluate the association of WBC count and new-onset PAD. The mean (+/-s.d.)
      baseline WBC count was 6.11+/-1.54 * 109 l-1, the mean (+/-s.d.) ABI was 1.11+/
      0.08 at baseline and the incidence of PAD was 2.7% over 2.3 years. WBC counts
      were significantly associated with PAD incidence (odds ratio (OR)=1.27, 95%
      confidence interval (CI): 1.14-1.41, P<0.0001) with every 1 * 109 l-1 increase in
      WBC count. This relationship remained significant (OR=1.21, 95% CI: 1.08-1.36,
      P=0.0014) even after adjusting for other variables. The highest WBC quartile
      group had increased risk when compared with the lowest quartile group (OR=2.14,
      95% CI: 1.09-4.22, P=0.027) in a multivariate logistic model. Furthermore, we did
      not find significant heterogeneity among the analyzed subgroups based on sex
      (male or female), age (<60 or ?60 years old), body mass index (BMI, <25 or ?25 kg
      m-2), current smoking, current drinking, hypertension, diabetes mellitus,
      dyslipidemia or cardiovascular disease. In conclusion, elevated WBC counts
      independently predict the risk of new-onset PAD in a Chinese community-based
      population, supporting the hypothesis that systemic inflammation plays an
      important role in PAD development.

PMID- 28490754
TI  - Effect of alkaline microwaving pretreatment on anaerobic digestion and biogas
      production of swine manure.
AB  - Microwave assisted with alkaline (MW-A) condition was applied in the pretreatment
      of swine manure, and the effect of the pretreatment on anaerobic treatment and
      biogas production was evaluated in this study. The two main microwaving (MW)
      parameters, microwaving power and reaction time, were optimized for the
      pretreatment. Response surface methodology (RSM) was used to investigate the
      effect of alkaline microwaving process for manure pretreatment at various values
      of pH and energy input. Results showed that the manure disintegration degree was
      maximized of 63.91% at energy input of 54 J/g and pH of 12.0, and variance
      analysis indicated that pH value played a more important role in the pretreatment
      than in energy input. Anaerobic digestion results demonstrated that MW-A
      pretreatment not only significantly increased cumulative biogas production, but
      also shortened the duration for a stable biogas production rate. Therefore, the
      alkaline microwaving pretreatment could become an alternative process for
      effective treatment of swine manure.

PMID- 28490755
TI  - Thigmotaxis Mediates Trail Odour Disruption.
AB  - Disruption of foraging using oversupply of ant trail pheromones is a novel pest
      management application under investigation. It presents an opportunity to
      investigate the interaction of sensory modalities by removal of one of the modes.
      Superficially similar to sex pheromone-based mating disruption in moths, ant
      trail pheromone disruption lacks an equivalent mechanistic understanding of how
      the ants respond to an oversupply of their trail pheromone. Since significant
      compromise of one sensory modality essential for trail following (chemotaxis) has
      been demonstrated, we hypothesised that other sensory modalities such as
      thigmotaxis could act to reduce the impact on olfactory disruption of foraging
      behaviour. To test this, we provided a physical stimulus of thread to aid
      trailing by Argentine ants otherwise under disruptive pheromone concentrations.
      Trail following success was higher using a physical cue. While trail integrity
      reduced under continuous over-supply of trail pheromone delivered directly on the
      thread, provision of a physical cue in the form of thread slightly improved trail
      following and mediated trail disruption from high concentrations upwind. Our
      results indicate that ants are able to use physical structures to reduce but not
      eliminate the effects of trail pheromone disruption.

PMID- 28490756
TI  - Expressing acetylcholine receptors after innervation suppresses spontaneous
      vesicle release and causes muscle fatigue.
AB  - The formation and function of synapses are tightly orchestrated by the precise
      timing of expression of specific molecules during development. In this study, we
      determined how manipulating the timing of expression of postsynaptic
      acetylcholine receptors (AChRs) impacts presynaptic release by establishing a
      genetically engineered zebrafish line in which we can freely control the timing
      of AChR expression in an AChR-less fish background. With the delayed induction of
      AChR expression after an extensive period of AChR-less development, paralyzed
      fish displayed a remarkable level of recovery, exhibiting a robust escape
      response following developmental delay. Despite their apparent behavioral rescue,
      synapse formation in these fish was significantly altered as a result of delayed
      AChR expression. Motor neuron innervation determined the sites for AChR
      clustering, a complete reversal of normal neuromuscular junction (NMJ)
      development where AChR clustering precedes innervation. Most importantly, among
      the three modes of presynaptic vesicle release, only the spontaneous release
      machinery was strongly suppressed in these fish, while evoked vesicle release
      remained relatively unaffected. Such a specific presynaptic change, which may
      constitute a part of the compensatory mechanism in response to the absence of
      postsynaptic AChRs, may underlie symptoms of neuromuscular diseases characterized
      by reduced AChRs, such as myasthenia gravis.

PMID- 28490757
TI  - Transcriptome and metabolite analysis identifies nitrogen utilization genes in
      tea plant (Camellia sinensis).
AB  - Applied nitrogen (N) fertilizer significantly increases the leaf yield. However,
      most N is not utilized by the plant, negatively impacting the environment. To
      date, little is known regarding N utilization genes and mechanisms in the leaf
      production. To understand this, we investigated transcriptomes using RNA-seq and
      amino acid levels with N treatment in tea (Camellia sinensis), the most popular
      beverage crop. We identified 196 and 29 common differentially expressed genes in
      roots and leaves, respectively, in response to ammonium in two tea varieties.
      Among those genes, AMT, NRT and AQP for N uptake and GOGAT and GS for N
      assimilation were the key genes, validated by RT-qPCR, which expressed in a
      network manner with tissue specificity. Importantly, only AQP and three novel
      DEGs associated with stress, manganese binding, and gibberellin-regulated
      transcription factor were common in N responses across all tissues and varieties.
      A hypothesized gene regulatory network for N was proposed. A strong statistical
      correlation between key genes' expression and amino acid content was revealed.
      The key genes and regulatory network improve our understanding of the molecular
      mechanism of N usage and offer gene targets for plant improvement.

PMID- 28490758
TI  - Identifying conformational changes with site-directed spin labeling reveals that
      the GTPase domain of HydF is a molecular switch.
AB  - [FeFe]-hydrogenases catalyse the reduction of protons to hydrogen at a complex
      2Fe[4Fe4S] center called H-cluster. The assembly of this active site is a
      multistep process involving three proteins, HydE, HydF and HydG. According to the
      current models, HydF has the key double role of scaffold, upon which the final H
      cluster precursor is assembled, and carrier to transfer it to the target
      hydrogenase. The X-ray structure of HydF indicates that the protein is a
      homodimer with both monomers carrying two functional domains: a C-terminal FeS
      cluster-binding domain, where the precursor is assembled, and a N-terminal GTPase
      domain, whose exact contribution to cluster biogenesis and hydrogenase activation
      is still elusive. We previously obtained several hints suggesting that the
      binding of GTP to HydF could be involved in the interactions of this scaffold
      protein with the other maturases and with the hydrogenase itself. In this work,
      by means of site directed spin labeling coupled to EPR/PELDOR spectroscopy, we
      explored the conformational changes induced in a recombinant HydF protein by GTP
      binding, and provide the first clue that the HydF GTPase domain could be involved
      in the H-cluster assembly working as a molecular switch similarly to other known
      small GTPases.

PMID- 28490759
TI  - Comorbidity burden of patients with Parkinson's disease and Parkinsonism between
      2003 and 2012: A multicentre, nationwide, retrospective study in China.
AB  - Parkinson's disease (PD) and Parkinsonism are common neurodegenerative disorders
      with continuously increasing prevalence, causing high global burdens. However,
      data concerning the comorbidity burden of patients with PD or Parkinsonism in
      China are lacking. To investigate the health condition and comorbidity burden, a
      total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary
      hospitals in seven cities across China from 2003 to 2012. Their comorbidity
      burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and
      Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and
      Parkinsonism patients. Compared with PD patients, Parkinsonism patients were
      older (69.8 +/- 11.5 vs. 67.9 +/- 11.4, P < 0.001); had a higher comorbidity
      burden, including ECI (1.1 +/- 1.2 vs. 1.0 +/- 1.2, P < 0.001) and CCI (1.3 +/-
      1.6 vs. 1.1 +/- 1.5, P < 0.001); and had higher hospitalization expenses. The ECI
      (1.1 +/- 1.3 vs. 0.9 +/- 1.1, P < 0.001) and CCI (1.3 +/- 1.6 vs. 0.9 +/- 1.2, P
      < 0.001) were higher in males than in females. The average length of stay and
      daily hospitalization expenses increased with age, as did ECI and CCI. This is
      the first study to report the disease burden of Chinese PD and Parkinsonism
      patients. It provides useful information to better understand their health
      status, and to raise the awareness of clinicians for providing better health
      care.

PMID- 28490760
TI  - Hormonal pleiotropy helps maintain queen signal honesty in a highly eusocial
      wasp.
AB  - In insect societies, both queens and workers produce chemicals that reliably
      signal caste membership and reproductive status. The mechanisms that help to
      maintain the honesty of such queen and fertility signals, however, remain poorly
      studied. Here we test if queen signal honesty could be based on the shared
      endocrine control of queen fertility and the production of specific signals. In
      support of this "hormonal pleiotropy" hypothesis, we find that in the common
      wasp, application of methoprene (a juveline hormone analogue) caused workers to
      acquire a queen-like cuticular hydrocarbon profile, resulting in the
      overproduction of known queen pheromones as well as some compounds typically
      linked to worker fertility. By contrast, administration of precocene-I (a JH
      inhibitor) had a tendency to have the opposite effect. Furthermore, a clear
      gonadotropic effect of JH in queens was suggested by the fact that circulating
      levels of JH were ca. 2 orders of magnitude higher in queens than those in
      workers and virgin, non-egg-laying queens, even if methoprene or precocene
      treatment did not affect the ovary development of workers. Overall, these results
      suggest that queen signal honesty in this system is maintained by queen fertility
      and queen signal production being under shared endocrine control.

PMID- 28490761
TI  - Nanoscale Brownian heating by interacting magnetic dipolar particles.
AB  - Clusters of magnetic nanoparticles have received considerable interest in various
      research fields. Their capacity to generate heat under an alternating magnetic
      field has recently opened the way to applications such as cancer therapy by
      hyperthermia. This work is an attempt to investigate the collective effects of
      interacting dipoles embedded in magnetic nano-particles (MNP) to predict their
      thermal dissipation with a liquid. We first present a general approach, based on
      the tracking of the microscopic dipole fluctuations, to access to the dissipation
      spectra of any spatial distribution of MNPs. Without any other assumption that
      the linear response regime, it is shown that increasing the particle
      concentration (dipolar interactions) dramatically diminishes and blueshifts the
      dissipation processes. This effect originates in a predominance of the coupling
      energy over the Brownian torques, which create a long-range ordering that
      saturates the response of the system to an external field. Consequently, the
      particle density is of fundamental importance to the control of the absorption of
      electromagnetic energy and its subsequent dissipation in the form of heat.

PMID- 28490762
TI  - Nexus fermions in topological symmorphic crystalline metals.
AB  - Topological metals and semimetals (TMs) have recently drawn significant interest.
      These materials give rise to condensed matter realizations of many important
      concepts in high-energy physics, leading to wide-ranging protected properties in
      transport and spectroscopic experiments. It has been well-established that the
      known TMs can be classified by the dimensionality of the topologically protected
      band degeneracies. While Weyl and Dirac semimetals feature zero-dimensional
      points, the band crossing of nodal-line semimetals forms a one-dimensional closed
      loop. In this paper, we identify a TM that goes beyond the above paradigms. It
      shows an exotic configuration of degeneracies without a well-defined
      dimensionality. Specifically, it consists of 0D nexus with triple-degeneracy that
      interconnects 1D lines with double-degeneracy. We show that, because of the novel
      form of band crossing, the new TM cannot be described by the established results
      that characterize the topology of the Dirac and Weyl nodes. Moreover, triply
      degenerate nodes realize emergent fermionic quasiparticles not present in
      relativistic quantum field theory. We present materials candidates. Our results
      open the door for realizing new topological phenomena and fermions including
      transport anomalies and spectroscopic responses in metallic crystals with
      nontrivial topology beyond the Weyl/Dirac paradigm.

PMID- 28490763
TI  - Methylglyoxal-induced glycation changes adipose tissue vascular architecture,
      flow and expansion, leading to insulin resistance.
AB  - Microvascular dysfunction has been suggested to trigger adipose tissue
      dysfunction in obesity. This study investigates the hypothesis that glycation
      impairs microvascular architecture and expandability with an impact on insulin
      signalling. Animal models supplemented with methylglyoxal (MG), maintained with a
      high-fat diet (HFD) or both (HFDMG) were studied for periepididymal adipose
      (pEAT) tissue hypoxia and local and systemic insulin resistance. Dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) was used to quantify blood flow in
      vivo, showing MG-induced reduction of pEAT blood flow. Increased adipocyte size
      and leptin secretion were observed only in rats feeding the high-fat diet,
      without the development of hypoxia. In turn, hypoxia was only observed when MG
      was combined (HFDMG group), being associated with impaired activation of the
      insulin receptor (Tyr1163), glucose intolerance and systemic and muscle insulin
      resistance. Accordingly, the adipose tissue angiogenic assay has shown decreased
      capillarization after dose-dependent MG exposure and glyoxalase-1 inhibition.
      Thus, glycation impairs adipose tissue capillarization and blood flow, hampering
      its expandability during a high-fat diet challenge and leading to hypoxia and
      insulin resistance. Such events have systemic repercussions in glucose metabolism
      and may lead to the onset of unhealthy obesity and progression to type 2
      diabetes.

PMID- 28490764
TI  - Progranulin deficiency causes the retinal ganglion cell loss during development.
AB  - Astrocytes are glial cells that support and protect neurons in the central
      nervous systems including the retina. Retinal ganglion cells (RGCs) are in
      contact with the astrocytes and our earlier findings showed the reduction of the
      number of cells in the ganglion cell layer in adult progranulin deficient mice.
      In the present study, we focused on the time of activation of the astrocytes and
      the alterations in the number of RGCs in the retina and optic nerve in
      progranulin deficient mice. Our findings showed that the number of Brn3a-positive
      cells was reduced and the expression of glial fibrillary acidic protein (GFAP)
      was increased in progranulin deficient mice. The progranulin deficient mice had a
      high expression of GFAP on postnatal day 9 (P9) but not on postnatal day 1. These
      mice also had a decrease in the number of the Brn3a-positive cells on P9. Taken
      together, these findings indicate that the absence of progranulin can affect the
      survival of RGCs subsequent the activation of astrocytes during retinal
      development.

PMID- 28490765
TI  - Effect of genomics-related literacy on non-communicable diseases.
AB  - Recent progress in genomic research has raised expectations for the development
      of personalized preventive medicine, although genomics-related literacy of
      patients will be essential. Thus, enhancing genomics-related literacy is crucial,
      particularly for individuals with low genomics-related literacy because they
      might otherwise miss the opportunity to receive personalized preventive care.
      This should be especially emphasized when a lack of genomics-related literacy is
      associated with elevated disease risk, because patients could therefore be
      deprived of the added benefits of preventive interventions; however, whether such
      an association exists is unclear. Association between genomics-related literacy,
      calculated as the genomics literacy score (GLS), and the prevalence of non
      communicable diseases was assessed using propensity score matching on 4646
      participants (males: 1891; 40.7%). Notably, the low-GLS group (score below
      median) presented a higher risk of hypertension (relative risk (RR) 1.09, 95%
      confidence interval (CI) 1.03-1.16) and obesity (RR 1.11, 95% CI 1.01-1.22) than
      the high-GLS group. Our results suggest that a low level of genomics-related
      literacy could represent a risk factor for hypertension and obesity. Evaluating
      genomics-related literacy could be used to identify a more appropriate population
      for health and educational interventions.

PMID- 28490766
TI  - SCA42 mutation analysis in a case series of Japanese patients with
      spinocerebellar ataxia.
AB  - Spinocerebellar ataxia (SCA) is a group of dominantly inherited heterogeneous
      disorders in which 43 subtypes have been identified to date. Recently, Japanese
      and French families with SCA type 42 (SCA42) were found to have a missense
      mutation (c.5144G>A; R1715H) in CACNA1G. We performed genetic analysis of 84
      unrelated families to find the prevalence of SCA42 in Japan. Two families were
      found to have the previously reported missense mutation. Clinical presentations
      of the affected members of these families were similar to those of the previously
      reported French and Japanese families. Our study demonstrates that SCA42 exists
      in small numbers in Japan, and further supports the idea that SCA42 is a slowly
      progressive, pure cerebellar ataxia.

PMID- 28490767
TI  - Biliverdin Reductase inhibitors did not improve severe unconjugated
      hyperbilirubinemia in vivo.
AB  - We aimed to identify potent biliverdin reductase (BVRA) inhibitors as a novel
      concept for the treatment of severe unconjugated hyperbilirubinemia. 1280 FDA
      approved compounds were screened in vitro for their ability to inhibit human and
      rat BVRA activity  and 2 6 compounds were identified as BVRA inhibitors .
      Montelukast and Disulfiram were sel ected as potentially clinically applicable
      drug s and tested to reduce serum unconjugated bilirubin (UCB) levels in the
      Ugt1a1-deficient rat, a model for chronic unconjugated hyperbilirubinemia. Oral
      administration of Disulfiram was toxic in the Ugt1a1-deficient rat (weight loss,
      transaminase elevation). Oral Montelukast administration led to low serum
      concentrations and did not alter serum UCB levels. Intraperitoneal injections of
      Mont elukast resulted in concentrations up to 110 MUmol/L in serum and 400
      MUmol/L in the liver. Still, serum UCB levels remained unaltered. This first
      study on biliverdin reductase inhibition as a novel concept for treatment of
      unconjugated hyperbilirubinemia identified putative in vitro BVRA inhibitors.
      Montelukast, the clinically most suitable inhibitor, did not result in reduction
      of serum UCB in the Ugt1a1-deficient rat. The proposed treatment strategy will
      not result in amelioration of severe unconjugated hyperbilirubinemia in humans
      without the identification or development of more potent BVRA inhibitors.

PMID- 28490768
TI  - Analytical evidence of enamel hypomineralisation on permanent and primary molars
      amongst past populations.
AB  - Molar Incisor Hypomineralisation (MIH) and Hypomineralised Second Primary Molars
      (HSPM) involve prevalent qualitative structural developmental anomalies of tooth
      enamel affecting the first permanent molars (and often incisors) and the second
      primary molars, respectively. These demarcated hypomineralised lesions of enamel
      manifest as white-cream or yellow-brown opacities, with possible post-eruptive
      localised loss of enamel. Aetiological hypotheses have involved contemporary life
      factors (i.e. environmental pollutant exposure or early childhood medications) in
      contrast to factors not limited to a specific time period (i.e. hypoxia at birth
      or genetic predisposition). Evidence of MIH in ancient populations would
      reinforce aetiological factors present for many centuries. By means of
      microtomographic and X-ray fluorescence analyses the present study provides
      evidence that (i) two archaeological specimens: "S407" (Sains-en-Gohelle, France,
      12th-16th centuries) and "B335" (Beauvais, France, 15th-18th centuries) were MIH
      affected, and (ii) one individual "S323" was affected by HSPM and MIH (Sains-en
      Gohelle, France, 7th-11th centuries).

PMID- 28490769
TI  - Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated
      with brain edema following fatal heat stroke.
AB  - Human brain samples were collected from 46 autopsy cases, including 23 fatal heat
      stroke cases and 23 age-matched controls. Nine candidate reference genes (PES1,
      POLR2A, IPO8, HMBS, SDHA, GAPDH, UBC, B2M, ACTB) were evaluated in the cerebral
      cortex of 10 forensic autopsy cases (5 heat stroke and 5 controls), using the
      geNorm module in qBaseplus software. SDHA, POLR2A, IPO8 and HMBS were identified
      as the most stable reference genes. Using these validated reference genes, mRNA
      expressions of Matrix metalloproteinases (MMPs, MMP2 and MMP9), Claudin5 (CLDN5),
      Occludin (OCLN), Zona occludens protein-1 (ZO1) and Aquaporins (AQPs, AQP1 and
      AQP4) in the cerebral cortex were examined. Relative mRNA quantification using
      Taqman real-time PCR assay demonstrated increased calibrated normalized relative
      quantity (CNRQ) values of MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke cases.
      Heat stroke cases showed an increase in brain water content, which was found to
      be positively correlated with MMP9, OCLN, ZO1 and CLDN5 mRNA. When using one
      conventional reference gene (GAPDH or ACTB) for normalization, no difference was
      detected between heat stroke and controls. In immunostaining, only AQP4 showed
      more intense staining in most heat stroke cases. The present study, for the first
      time, reports increased cerebral MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke
      and suggest a crucial role of reference gene selection when using postmortem
      human tissues.

PMID- 28490770
TI  - Misoprostol for medical treatment of missed abortion: a systematic review and
      network meta-analysis.
AB  - The efficacy and safety of misoprostol alone for missed abortion varied with
      different regimens. To evaluate existing evidence for the medical management of
      missed abortion using misoprostol, we undertook a comprehensive review and meta
      analysis. The electronic literature search was conducted using PubMed, the
      Cochrane Library, Embase, EBSCOhost Online Research Databases, Springer Link,
      ScienceDirect, Web of Science, Ovid Medline and Google Scholar. 18 studies of
      1802 participants were included in our analysis. Compared with vaginal
      misoprostol of 800 ug or sublingual misoprostol of 600 ug, lower-dose regimens
      (200 ug or 400 ug) by any route of administration tend to be significantly less
      effective in producing abortion within about 24 hours. In terms of efficacy, the
      most effective treatment was sublingual misoprostol of 600 ug and the least
      effective was oral misoprostol of 400 ug. In terms of tolerability, vaginal
      misoprostol of 400 ug was reported with fewer side effects and sublingual
      misoprostol of 600 ug was reported with more side effects. Misoprostol is a non
      invasive, effective medical method for completion of abortion in missed abortion.
      Sublingual misoprostol of 600 ug or vaginal misoprostol of 800 ug may be a good
      choice for the first dose. The ideal dose and medication interval of misoprostol
      however needs to be further researched.

PMID- 28490771
TI  - Some dietary factors can modulate the effect of the zinc transporters 8
      polymorphism on the risk of metabolic syndrome.
AB  - There are conflicting data on the impact of zinc transporter 8 (ZNT8) gene
      variations on the metabolic syndrome (MetS). Hence, the effects of the
      interaction between rs13266634 and dietary factors on the risk of MetS were
      investigated in this study. Subjects of this nested case-control study were
      selected from the participants in Tehran Lipid and Glucose Study. Each of the
      cases (n = 817) was individually matched with a control. Dietary patterns were
      determined using factor analysis. The ZNT8 rs13266634 were genotyped by the Tetra
      refractory mutation system-polymerase chain reaction analysis. Two dietary
      patterns were extracted. There were no significant interactions between the ZNT8
      SNP and the dietary patterns on the risk of MetS or its components. An
      interaction was observed between rs13266634 and the omega-3 fatty acid intakes on
      the risk of MetS in subjects with the CC genotype (P interaction < 0.01). Zinc
      modified the association of the ZNT8 variant with high fasting blood sugar (P
      interaction = 0.05) in CC genotype carriers. An interaction was also observed
      between rs13266634 and salty snacks at the risk of abdominal obesity (P
      interaction < 0.05). Our findings suggest an interaction between omega-3 fatty
      acids, zinc, salty snacks and rs13266634, which may affect the risk of MetS or
      its components.

PMID- 28490772
TI  - Flexible and compact hybrid metasurfaces for enhanced ultra high field in vivo
      magnetic resonance imaging.
AB  - Developments in metamaterials and related structures such as metasurfaces have
      opened up new possibilities in designing materials and devices with unique
      properties. Here we report a new hybrid metasurface structure, comprising a two
      dimensional metamaterial surface and a very high permittivity dielectric
      substrate, that has been designed to enhance the local performance of an ultra
      high field MRI scanner. This new flexible and compact resonant structure is the
      first metasurface which can be integrated with multi-element close-fitting
      receive coil arrays that are used for all clinical MRI scans. We demonstrate the
      utility of the metasurface acquiring in-vivo human brain images and proton MR
      spectra with enhanced local sensitivity on a commercial 7 Tesla system.

PMID- 28490773
TI  - Rapid face adaptation distributes representation in inferior-temporal cortex
      across time and neuronal dimensions.
AB  - Neuronal networks of the brain adapt their information processing according to
      the history of stimuli. Whereas most studies have linked adaptation to repetition
      suppression, recurrent connections within a network and disinhibition due to
      adaptation predict more complex response patterns. The main questions of this
      study are as follows: what is the effect of the selectivity of neurons on
      suppression/enhancement of neural responses? What are the consequences of
      adaptation on information representation in neural population and the temporal
      structure of response patterns? We studied rapid face adaptation using spiking
      activities of neurons in the inferior-temporal (IT) cortex. Investigating the
      responses of neurons, within a wide range from negative to positive face
      selectivity, showed that despite the peak amplitude suppression in highly
      positive selective neurons, responses were enhanced in most other neurons. This
      enhancement can be attributed to disinhibition due to adaptation. Delayed and
      distributed responses were observed for positive selective neurons. Principal
      component analysis of the IT population responses over time revealed that
      repetition of face stimuli resulted in temporal decorrelation of the network
      activity. The contributions of the main and higher neuronal dimensions were
      changed under an adaptation condition, where more neuronal dimensions were used
      to encode repeated face stimuli.

PMID- 28490774
TI  - DMBA acts on cumulus cells to desynchronize nuclear and cytoplasmic maturation of
      pig oocytes.
AB  - As an environmental pollutant and carcinogen, 7,12-dimethylbenz[a]anthracene
      (DMBA) can destroy ovarian follicles at all developmental stages in rodents.
      However, the underlying molecular mechanism remains obscure. In the present
      study, we aim to address how DMBA affects the in vitro maturation and development
      of porcine oocytes. We discovered that for 20 MUM DMBA-treated cumulus-oocyte
      complexes (COCs), the rate of oocyte germinal vesicle breakdown (GVBD) was
      significantly altered, and the extrusion rate of first polar body was increased.
      Moreover, oocytes from 20 MUM DMBA-treated COCs had significant down-regulation
      of H3K9me3 and H3K27me3, up-regulation of H3K36me3, higher incidence of DNA
      double strand breaks (DSBs) and early apoptosis. In striking contrast, none of
      these changes happened to 20 MUM DMBA-treated cumulus-denuded oocytes (CDOs).
      Furthermore, 20 MUM DMBA treatment increased the reactive oxygen species (ROS)
      level, decreased mitochondrial membrane potential (Delta Psim), and inhibited
      developmental competence for oocytes from both COC and CDO groups. Collectively,
      our data indicate DMBA could act on cumulus cells via the gap junction to disturb
      the synchronization of nuclear and ooplasmic maturation, and reduce the
      developmental competence of oocytes.

PMID- 28490775
TI  - Metasurface Freeform Nanophotonics.
AB  - Freeform optics aims to expand the toolkit of optical elements by allowing for
      more complex phase geometries beyond rotational symmetry. Complex, asymmetric
      curvatures are employed to enhance the performance of optical components while
      minimizing their size. Unfortunately, these high curvatures and complex forms are
      often difficult to manufacture with current technologies, especially at the
      micron scale. Metasurfaces are planar sub-wavelength structures that can control
      the phase, amplitude, and polarization of incident light, and can thereby mimic
      complex geometric curvatures on a flat, wavelength-scale thick surface. We
      present a methodology for designing analogues of freeform optics using a silicon
      nitride based metasurface platform for operation at visible wavelengths. We
      demonstrate a cubic phase plate with a point spread function exhibiting enhanced
      depth of field over 300 micron along the optical axis with potential for
      performing metasurface-based white light imaging, and an Alvarez lens with a
      tunable focal length range of over 2.5 mm corresponding to a change in optical
      power of ~1600 diopters with 100 micron of total mechanical displacement. The
      adaptation of freeform optics to a sub-wavelength metasurface platform allows for
      further miniaturization of optical components and offers a scalable route toward
      implementing near-arbitrary geometric curvatures in nanophotonics.

PMID- 28490776
TI  - Learning and memory: Consolidation circuitry.

PMID- 28490777
TI  - Working memory: Keeping short-term memories alive.

PMID- 28490778
TI  - Brain ageing: A youthful reminder.

PMID- 28490779
TI  - Large scale phosphoprotein profiling to explore Drosophila cold acclimation
      regulatory mechanisms.
AB  - The regulatory mechanisms involved in the acquisition of thermal tolerance are
      unknown in insects. Reversible phosphorylation is a widespread post-translational
      modification that can rapidly alter proteins function(s). Here, we conducted a
      large-scale comparative screening of phosphorylation networks in adult Drosophila
      flies that were cold-acclimated versus control. Using a modified SIMAC method
      followed by a multiple MS analysis strategy, we identified a large collection of
      phosphopeptides (about 1600) and phosphoproteins (about 500) in both groups, with
      good enrichment efficacy (80%). The saturation curves from the four biological
      replicates revealed that the phosphoproteome was rather well covered under our
      experimental conditions. Acclimation evoked a strong phosphoproteomic signal
      characterized by large sets of unique and differential phosphoproteins. These
      were involved in several major GO superclusters of which cytoskeleton
      organization, positive regulation of transport, cell cycle, and RNA processing
      were particularly enriched. Data suggest that phosphoproteomic changes in
      response to acclimation were mainly localized within cytoskeletal network, and
      particularly within microtubule associated complexes. This study opens up novel
      research avenues for exploring the complex regulatory networks that lead to
      acquired thermal tolerance.

PMID- 28490780
TI  - Intrabasin Variability of East Pacific Tropical Cyclones During ENSO Regulated by
      Central American Gap Winds.
AB  - Hurricane Patricia in 2015 was the strongest Pacific hurricane to make landfall
      in Mexico. Although Patricia fortuitously spared major cities, it reminded us of
      the threat tropical cyclones (TCs) pose in the eastern North Pacific (ENP) and
      the importance of improving our understanding and prediction of ENP TCs.
      Patricia's intensity and the active 2015 ENP hurricane season have been partially
      attributed to the strong El Nino in 2015, however there is still a lack of
      fundamental understanding of the relationship between El Nino-Southern
      Oscillation (ENSO) and ENP TCs. Here, we demonstrate that ENSO drives intrabasin
      variability of ENP TCs, with enhanced (reduced) TC frequency in the western
      portion of the ENP during El Nino (La Nina), but reduced (enhanced) TC frequency
      in the eastern nearshore area, where landfalling TCs preferentially form. This
      intrabasin difference is primarily driven by the Central American Gap Winds
      (CAGW), which intensify (weaken) during El Nino (La Nina), producing low-level
      anticyclonic (cyclonic) relative vorticity anomalies and thus an unfavorable
      (favorable) environment for TC genesis. These findings shed new light on the
      dynamics linking ENP TC activity to ENSO, and highlight the importance of
      improving CAGW representation in models to make skillful seasonal forecasts of
      ENP TCs.

PMID- 28490781
TI  - Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and
      Correlated with BRAFV600E Mutation by Bioinformatics Integrative Analysis.
AB  - Papillary Thyroid Cancer (PTC) is an endocrine malignancy in which BRAFV600E
      oncogenic mutation induces the most aggressive phenotype. In this way,
      considering that lncRNAs are arising as key players in oncogenesis, it is of high
      interest the identification of BRAFV600E-associated long noncoding RNAs, which
      can provide possible candidates for secondary mechanisms of BRAF-induced
      malignancy in PTC. In this study, we identified differentially expressed lncRNAs
      correlated with BRAFV600E in PTC and, also, extended the cohort of paired normal
      and PTC samples to more accurately identify differentially expressed lncRNAs
      between these conditions. Indirectly validated targets of the differentially
      expressed lncRNAs in PTC compared to matched normal samples demonstrated an
      involvement in surface receptors responsible for signal transduction and cell
      adhesion, as well as, regulation of cell death, proliferation and apoptosis.
      Targets of BRAFV600E-correlated lncRNAs are mainly involved in calcium signaling
      pathway, ECM-receptor interaction and MAPK pathway. In summary, our study
      provides candidate lncRNAs that can be either used for future studies related to
      diagnosis/prognosis or as targets for PTC management.

PMID- 28490782
TI  - Mangrove dieback during fluctuating sea levels.
AB  - Recent evidence indicates that climate change and intensification of the El Nino
      Southern Oscillation (ENSO) has increased variation in sea level. Although
      widespread impacts on intertidal ecosystems are anticipated to arise from the sea
      level seesaw associated with climate change, none have yet been demonstrated.
      Intertidal ecosystems, including mangrove forests are among those ecosystems that
      are highly vulnerable to sea level rise, but they may also be vulnerable to sea
      level variability and extreme low sea level events. During 16 years of monitoring
      of a mangrove forest in Mangrove Bay in north Western Australia, we documented
      two forest dieback events, the most recent one being coincident with the large
      scale dieback of mangroves in the Gulf of Carpentaria in northern Australia.
      Diebacks in Mangrove Bay were coincident with periods of very low sea level,
      which were associated with increased soil salinization of 20-30% above pre-event
      levels, leading to canopy loss, reduced Normalized Difference Vegetation Index
      (NDVI) and reduced recruitment. Our study indicates that an intensification of
      ENSO will have negative effects on some mangrove forests in parts of the Indo
      Pacific that will exacerbate other pressures.

PMID- 28490784
TI  - Osteoarthritis: Removing old chondrocytes to combat disease.

PMID- 28490783
TI  - Multiple biomarker responses (serum biochemistry, oxidative stress, genotoxicity
      and histopathology) in Channa punctatus exposed to heavy metal loaded waste
      water.
AB  - Experiments were conducted to investigate the health of fish Channa punctatus
      inhabiting heavy metal-loaded waste water. Heavy metals in the order of Fe > Mn >
      Zn > Co > Ni > Cu = Cr were present in the waste water. Gills had high metal load
      followed by liver and then kidney. Albumin, albumin to globulin (A:G) ratio,
      triglyceride, high density lipoprotein (HDL) and very low density lipoprotein
      (VLDL) were found to be lower but phospholipid, low density lipoprotein (LDL),
      total protein, lipid and cholesterol were higher as compared to the reference.
      Oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT),
      glutathione S transferase (GST) and lipid peroxidation (LPO) were significantly
      higher in all tissues, whereas reduced glutathione (GSH) levels were
      comparatively low. Damage to DNA was observed with significantly higher mean tail
      length of comets in the exposed fish gill cells (30.9 um) followed by liver (24.3
      um) and kidney (20.6 um) as compared to reference fish (5.2, 4.8 and 5.9 um
      respectively). Histopathology in gill, liver and kidney also showed marked
      damage. Integrated biochemical, oxidative stress, genotoxicity and
      histopathological findings are valuable biomarkers for native fish adaptive
      patterns, and monitoring of water quality/pollution of freshwater ecosystems.

PMID- 28490786
TI  - Rheumatoid arthritis: Don't swallow the NETs.

PMID- 28490785
TI  - The rise of IL-2 therapy - a picture beyond Treg cells.

PMID- 28490787
TI  - The changing face of polyarteritis nodosa and necrotizing vasculitis.
AB  - Polyarteritis nodosa (PAN) is a vasculitic disease characterized primarily by
      necrotizing vasculitis - inflammatory lesions in blood vessels that lead to
      vessel wall necrosis. Our understanding of PAN and necrotizing vasculitis has
      evolved over time. In addition to PAN, necrotizing vasculitis is now a recognized
      feature of a broad range of diseases with different aetiopathogenesis. For
      example, necrotizing vasculitis associated with hepatitis B virus infection has a
      different aetiopathogeneis to PAN and is now classified as a separate disease.
      Additionally, although 'classic' PAN is not an inherited disease, mutations in
      specific genes, such as ADA2 (also known as CECR1), can result in a necrotizing
      vasculopathy similar to PAN. The literature also suggests that the course of PAN
      differs in childhood-onset disease and in cases confined to the skin (so-called
      cutaneous PAN). Dissecting PAN and other autoinflammatory diseases with PAN-like
      features has enabled more-specific therapies and might also help us better
      understand the pathogenesis of these devastating conditions.

PMID- 28490788
TI  - Low-dose IL-2 therapy - a complex scenario that remains to be further explored.

PMID- 28490789
TI  - Epidemiology: Time to revisit the concept of reactive arthritis.

PMID- 28490790
TI  - Entropy of radiation: the unseen side of light.
AB  - Despite the fact that 2015 was the international year of light, no mention was
      made of the fact that radiation contains entropy as well as energy, with
      different spectral distributions. Whereas the energy function has been vastly
      studied, the radiation entropy distribution has not been analysed at the same
      speed. The Mode of the energy distribution is well known -Wien's law- and
      Planck's law has been analytically integrated recently, but no similar advances
      have been made for the entropy. This paper focuses on the characterization of the
      entropy of radiation distribution from an statistical perspective, obtaining a
      Wien's like law for the Mode and integrating the entropy for the Median and the
      Mean in polylogarithms, and calculating the Variance, Skewness and Kurtosis of
      the function. Once these features are known, the increasing importance of
      radiation entropy analysis is evidenced in three different interdisciplinary
      applications: defining and determining the second law Photosynthetically Active
      Radiation (PAR) region efficiency, measuring the entropy production in the
      Earth's atmosphere, and showing how human vision evolution was driven by the
      entropy content in radiation.

PMID- 28490791
TI  - Intact word processing in developmental prosopagnosia.
AB  - A wealth of evidence from behavioural, neuropsychological and neuroimaging
      research supports the view that face recognition is reliant upon a domain
      specific network that does not process words. In contrast, the recent many-to
      many model of visual recognition posits that brain areas involved in word and
      face recognition are functionally integrated. Developmental prosopagnosia (DP) is
      characterised by severe deficits in the recognition of faces, which the many-to
      many model predicts should negatively affect word recognition. Alternatively,
      domain-specific accounts suggest that impairments in face and word processing
      need not go hand in hand. To test these possibilities, we ran a battery of 7
      tasks examining word processing in a group of DP cases and controls. One of our
      prosopagnosia cases exhibited a severe reading impairment with delayed response
      times during reading aloud tasks, but not lexical decision tasks. Overall,
      however, we found no evidence of global word processing deficits in DP,
      consistent with a dissociation account for face and word processing.

PMID- 28490792
TI  - Length effects on the dynamic process of cellular uptake and exocytosis of single
      walled carbon nanotubes in murine macrophage cells.
AB  - Cellular uptake and exocytosis of SWCNTs are fundamental processes determining
      their intracellular concentration and effects. Despite the great potential of
      acid-oxidized SWCNTs in biomedical field, understanding of the influencing
      factors on these processes needs to be deepened. Here, we quantitatively
      investigated uptake and exocytosis of SWCNTs in three lengths-630 (+/-171) nm (L
      SWCNTs), 390 (+/-50) nm (M-SWCNTs), and 195 (+/-63) nm (S-MWCNTs) in macrophages.
      The results showed that the cellular accumulation of SWCNTs was a length
      independent process and non-monotonic in time, with the most SWCNTs (3950
      fg/cell) accumulated at 8 h and then intracellular SWCNTs dropped obviously with
      time. The uptake rate of SWCNTs decreased with increasing concentration,
      suggesting that intracellular SWCNTs accumulation is a saturable process. After
      refreshing culture medium, we found increasing SWCNTs in supernatant and
      decreasing intracellular SWCNTs over time, confirming the exocytosis occurred.
      Selective inhibition of endocytosis pathways showed that the internalization of
      SWCNTs involves several pathways, in the order of macropinocytosis> caveolae
      mediated endocytosis> clathrin-dependent endocytosis. Intriguingly, clathrin
      mediated endocytosis is relatively important for internalizing shorter SWCNTs.
      The dynamic processes of SWCNTs uptake and exocytosis and the mechanisms revealed
      by this study may render a better understanding on SWCNT toxicity and facilitate
      the design of CNT products with mitigated toxicity and desired functions.

PMID- 28490793
TI  - Campanile Near-Field Probes Fabricated by Nanoimprint Lithography on the Facet of
      an Optical Fiber.
AB  - One of the major challenges to the widespread adoption of plasmonic and nano
      optical devices in real-life applications is the difficulty to mass-fabricate
      nano-optical antennas in parallel and reproducible fashion, and the capability to
      precisely place nanoantennas into devices with nanometer-scale precision. In this
      study, we present a solution to this challenge using the state-of-the-art
      ultraviolet nanoimprint lithography (UV-NIL) to fabricate functional optical
      transformers onto the core of an optical fiber in a single step, mimicking the
      'campanile' near-field probes. Imprinted probes were fabricated using a custom
      built imprinter tool with co-axial alignment capability with sub <100 nm position
      accuracy, followed by a metallization step. Scanning electron micrographs confirm
      high imprint fidelity and precision with a thin residual layer to facilitate
      efficient optical coupling between the fiber and the imprinted optical
      transformer. The imprinted optical transformer probe was used in an actual NSOM
      measurement performing hyperspectral photoluminescence mapping of standard
      fluorescent beads. The calibration scans confirmed that imprinted probes enable
      sub-diffraction limited imaging with a spatial resolution consistent with the gap
      size. This novel nano-fabrication approach promises a low-cost, high-throughput,
      and reproducible manufacturing of advanced nano-optical devices.

PMID- 28490794
TI  - Thermally induced micro-motion by inflection in optical potential.
AB  - Recent technological progress in a precise control of optically trapped objects
      allows much broader ventures to unexplored territory of thermal motion in non
      linear potentials. In this work, we exploit an experimental set-up of holographic
      optical tweezers to experimentally investigate Brownian motion of a micro
      particle near the inflection point of the cubic optical potential. We present two
      complementary views on the non-linear Brownian motion. On an ensemble of
      stochastic trajectories, we simultaneously determine (i) the detailed short-time
      position statistics and (ii) the long-distance first-passage time statistics. We
      evaluate specific statistical moment ratios demonstrating strongly non-linear
      stochastic dynamics. This is a crucial step towards a possible massive
      exploitation of the broad class of complex non-linear stochastic effects with
      objects of more complex structure and shape including living ones.

PMID- 28490795
TI  - Performances of Kevlar and Polyethylene as radiation shielding on-board the
      International Space Station in high latitude radiation environment.
AB  - Passive radiation shielding is a mandatory element in the design of an integrated
      solution to mitigate the effects of radiation during long deep space voyages for
      human exploration. Understanding and exploiting the characteristics of materials
      suitable for radiation shielding in space flights is, therefore, of primary
      importance. We present here the results of the first space-test on Kevlar and
      Polyethylene radiation shielding capabilities including direct measurements of
      the background baseline (no shield). Measurements are performed on-board of the
      International Space Station (Columbus modulus) during the ALTEA-shield ESA
      sponsored program. For the first time the shielding capability of such materials
      has been tested in a radiation environment similar to the deep-space one, thanks
      to the feature of the ALTEA system, which allows to select only high latitude
      orbital tracts of the International Space Station. Polyethylene is widely used
      for radiation shielding in space and therefore it is an excellent benchmark
      material to be used in comparative investigations. In this work we show that
      Kevlar has radiation shielding performances comparable to the Polyethylene ones,
      reaching a dose rate reduction of 32 +/- 2% and a dose equivalent rate reduction
      of 55 +/- 4% (for a shield of 10 g/cm2).

PMID- 28490796
TI  - Degradation mechanisms of silver nanowire electrodes under ultraviolet
      irradiation and heat treatment.
AB  - We report the degradation mechanisms of the silver nanowire (Ag NW) electrodes
      that play a significantly important role in the stability of wearable and
      flexible devices. The degradation mechanisms behind the increase in the sheet
      resistances of Ag NW electrodes were clarified by investigating the variations in
      the structure and the chemical composition of the Ag NW electrodes caused by
      ultraviolet irradiation and thermal treatment. While the shapes of the Ag NWs
      were affected by melting during the thermal degradation process, the chemical
      composition of the polyvinylpyrrolidone protective layer on the surfaces of the
      Ag NWs was not changed. Ultraviolet irradiation deformed the shapes of the Ag NWs
      because nitrogen or oxygen atoms were introduced to the silver atoms on the
      surfaces of the Ag NWs. A graphene-oxide flake was coated on the Ag NW electrodes
      by using a simple dipping method to prevent ultraviolet irradiation and ozone
      contact with the surfaces of the Ag NWs, and the increase in the sheet resistance
      in the graphene-oxide-treated Ag NWs was suppressed. These observations will be
      of assistance to researchers trying to find novel ways to improve the stability
      of the Ag NW electrodes in next-generation wearable devices.

PMID- 28490797
TI  - Action on diabetic macular oedema: achieving optimal patient management in
      treating visual impairment due to diabetic eye disease.
AB  - This paper identifies best practice recommendations for managing diabetes and
      sight-threatening diabetic eye disease. The authors provide an update for
      ophthalmologists and allied healthcare professionals on key aspects of diabetes
      management, supported by a review of the pertinent literature, and recommend
      practice principles for optimal patient management in treating visual impairment
      due to diabetic eye disease. In people with diabetes, early optimal glycaemic
      control reduces the long-term risk of both microvascular and macrovascular
      complications. The authors propose more can and should be done to maximise
      metabolic control, promote appropriate behavioural modifications and encourage
      timely treatment intensification when indicated to ameliorate diabetes-related
      complications. All people with diabetes should be screened for sight-threatening
      diabetic retinopathy promptly and regularly. It is shown that attitudes towards
      treatment adherence in diabetic macular oedema appear to mirror patients' views
      and health behaviours towards the management of their own diabetes. Awareness of
      diabetic macular oedema remains low among people with diabetes, who need access
      to education early in their disease about how to manage their diabetes to delay
      progression and possibly avoid eye-related complications. Ophthalmologists and
      allied healthcare professionals play a vital role in multidisciplinary diabetes
      management and establishment of dedicated diabetic macular oedema clinics is
      proposed. A broader understanding of the role of the diabetes specialist nurse
      may strengthen the case for comprehensive integrated care in ophthalmic practice.
      The recommendations are based on round table presentations and discussions held
      in London, UK, September 2016.

PMID- 28490799
TI  - Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG.
AB  - Bioactive natural products from mangrove-derived actinomycetes are important
      sources for discovery of drug lead compounds. In this study, an extract prepared
      from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove
      soils was found to have activity in inhibiting proliferation of glioma cells.
      Large culture of this mangrove actinomycete in Gause's liquid medium resulted in
      isolation of seven novel polyene-polyol macrolides, named as flavofungins III-IX
      (3-9), together with known flavofungins I (1) and II (2) and spectinabilin (10).
      Structures of these isolated compounds were elucidated by extensive NMR analyses
      and HRESIMS data. The stereochemical assignments were achieved by a combination
      of NOE information, universal NMR database, and chemical reactions including
      preparation of acetonide derivatives and Mosher esters. Flavofungins IV-VIII (4
      8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring,
      while flavofungin IX (9) represents the first example of this type of macrolide
      with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10)
      showed anti-glioma and antifungal activities.

PMID- 28490798
TI  - Enhancing the Oxidation of Toluene with External Electric Fields: a Reactive
      Molecular Dynamics Study.
AB  - The effects of external electric field (Efield) on chemical reactions were
      studied with the reactive molecular dynamics (ReaxFF MD) simulations by using the
      oxidation of toluene as a model system. We observed that Efields may greatly
      enhance the oxidation rate of toluene. The initial reaction time of toluene is
      also reduced remarkably in Efields. A stronger Efield leads to a faster oxidation
      rate of toluene. Further studies reveal that the applying of a Efield may result
      in the oxidation of toluene at 2100 K which is otherwise not able to happen when
      the Efield is not present. The oxidation rate of toluene at 2100 K in a Efield is
      comparable with the oxidation rate of toluene at 2900 K when the Efield is not
      applied. In addition, Efields were observed to significantly enhance the
      occurrence of the initial radical generation for different pathways of toluene
      oxidation but they do not seem to favor any of the pathways. Finally, Efields do
      not seem to enhance the polarization of toluene during its transition state,
      which suggests that a polarizable charge equilibration method (PQEq) method might
      be needed to take the effects of Efields into consideration.

PMID- 28490800
TI  - The formation mechanism of tear strips on stretched Ti-22Al-25Nb alloy sheets.
AB  - This paper reports the presence of tear strips on the surface of a Ti-22Al-25Nb
      alloy sheet stretched at 960  degrees C. The test piece reveals a "bamboo"-shaped
      pattern on its surface, which severely affects the quality of the alloy.
      Microstructure analysis indicates that the formation mechanism of the tear strip
      is related to both the rich alpha2 phase layer and the interfacial B2 phase
      dynamic recrystallization layer between the alpha2 phase layer and the substrate
      metal.

PMID- 28490801
TI  - Dendritic cells provide a therapeutic target for synthetic small molecule
      analogues of the parasitic worm product, ES-62.
AB  - ES-62, a glycoprotein secreted by the parasitic filarial nematode
      Acanthocheilonema viteae, subverts host immune responses towards anti
      inflammatory phenotypes by virtue of covalently attached phosphorylcholine (PC).
      The PC dictates that ES-62 exhibits protection in murine models of inflammatory
      disease and hence a library of drug-like PC-based small molecule analogues (SMAs)
      was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were
      found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated
      molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF
      kappaB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86.
      Active SMAs also resulted in a DC phenotype that exhibited reduced capacity to
      prime antigen (Ag)-specific IFN-gamma production during co-culture with naive
      transgenic TCR DO.11.10 T cells in vitro and reduced their ability, following
      adoptive transfer, to prime the expansion of Ag-specific T lymphocytes,
      specifically TH17 cells, in vivo. Consistent with this, mice receiving DCs
      treated with SMAs exhibited significantly reduced severity of collagen-induced
      arthritis and this was accompanied by a significant reduction in IL-17+ cells in
      the draining lymph nodes. Collectively, these studies indicate that drug-like
      compounds that target DCs can be designed from parasitic worm products and
      demonstrate the potential for ES-62 SMA-based DC therapy in inflammatory disease.

PMID- 28490802
TI  - Transcriptome analysis of dominant-negative Brd4 mutants identifies Brd4-specific
      target genes of small molecule inhibitor JQ1.
AB  - The bromodomain protein Brd4 is an epigenetic reader and plays a critical role in
      the development and maintenance of leukemia. Brd4 binds to acetylated histone
      tails and activates transcription by recruiting the positive elongation factor P
      TEFb. Small molecule inhibitor JQ1 competitively binds the bromodomains of Brd4
      and displaces the protein from acetylated histones. However, it remains unclear
      whether genes targeted by JQ1 are mainly regulated by Brd4 or by other
      bromodomain proteins such as Brd2 and Brd3. Here, we describe anti-proliferative
      dominant-negative Brd4 mutants that compete with the function of distinct Brd4
      domains. We used these Brd4 mutants to compare the Brd4-specific transcriptome
      with the transcriptome of JQ1-treated cells. We found that most JQ1-regulated
      genes are also regulated by dominant-negative Brd4 mutants, including the mutant
      that competes with the P-TEFb recruitment function of Brd4. Importantly, JQ1 and
      dominant-negative Brd4 mutants regulated the same set of target genes of c-Myc, a
      key regulator of the JQ1 response in leukemia cells. Our results suggest that
      Brd4 mediates most of the anti-cancer effects of JQ1 and that the major function
      of Brd4 in this process is the recruitment of P-TEFb. In summary, our studies
      define the molecular targets of JQ1 in more detail.

PMID- 28490803
TI  - Effects of smoking and smoking abstinence on spatial vision in chronic heavy
      smokers.
AB  - Cigarette smoke is a complex chemical mixture, involving health-damaging
      components such as carbon monoxide, ammonia, pyridine, toluene and nicotine.
      While cognitive functions have been well documented in heavy smokers, spatial
      vision has been less characterized. In the article, we investigated smoking
      effects through contrast sensitivity function (CSF), a rigorous procedure that
      measures the spatial vision. Data were recorded from 48 participants, a group of
      non-smokers (n = 16), a group of chronic and heavy cigarette smokers (n = 16) and
      deprived smokers (n = 16); age range 20-45 years. Sinewave gratings with spatial
      frequencies ranging from 0.25 to 20 cycles per degree were used. All subjects
      were free from any neurological disorder, identifiable ocular disease and had
      normal acuity. No abnormalities were detected in the fundoscopic examination and
      in the optical coherence tomography exam. Contrary to expectations, performance
      on CSF differed between groups. Both smokers and deprived smokers presented a
      loss of contrast sensitivity compared to non-smokers. Post-hoc analyses suggest
      that deprived smokers were less sensitive at all spatial frequencies. These
      results suggest that not only chronic exposure to cigarette compounds but also
      withdrawal from nicotine affected spatial vision. This highlights the importance
      of understanding diffuse effects of smoking compounds on visual spatial
      processing.

PMID- 28490804
TI  - Epitaxial growth of Cu(001) thin films onto Si(001) using a single-step HiPIMS
      process.
AB  - We report on a new route to grow epitaxial copper (Cu) ultra-thin films (up to
      150 nm thick) at ambient temperature on Si(001) wafers covered with native oxide
      without any prior chemical etching or plasma cleaning of the substrate. It
      consists of a single-step deposition process using high power impulse magnetron
      sputtering (HiPIMS) and substrate biasing. For a direct current (DC) substrate
      bias voltage of -130 V, Cu/Si heteroepitaxial growth is achieved by HiPIMS
      following the Cu(001) [100]//Si(001) [110] orientation, while under the same
      average deposition conditions, but using conventional DC magnetron sputtering,
      polycrystalline Cu films with [111] preferred orientation are deposited. In
      addition, the intrinsic stress has been measured in situ during growth by real
      time monitoring of the wafer curvature. For this particular HiPIMS case, the
      stress is slightly compressive (-0.1 GPa), but almost fully relaxes after growth
      is terminated. As a result of epitaxy, the Cu surface morphology exhibits a
      regular pattern consisting of square-shaped mounds with a lateral size of
      typically 150 nm. For all samples, X-ray diffraction pole figures and
      scanning/transmission electron microscopy reveal the formation of extensive
      twinning of the Cu {111} planes.

PMID- 28490805
TI  - A Skint6 allele potentially contributes to mouse lupus.
AB  - Our previous study uncovered that the overlapping region of murine lupus
      susceptibility Sle2c1rec1a and Sle2c1rec1d subloci is strongly associated with
      lymphadenopathy and systemic autoimmunity. In order to identify the specific
      candidate gene, we generated a novel shorter recombinant, named as Sle2c1re1d1
      (rec1d1), from Sle2c1rec1d sublocus (rec1d). The rec1d1 interval corresponds
      precisely to the overlapping region of Sle2c1rec1a and Sle2c1rec1d subloci.
      Functionally, this rec1d1 sublocus showed a strong epistatic interaction with
      lpr, similar to that seen with Sle2c1rec1a or.Sle2c1rec1d. The Skint6 gene in the
      red1d1 interval was identified to have a point mutation, which inserts a
      premature stop codon and converts the membrane Skint6 protein into a truncated
      secretory peptide. However, other protein-coding genes in the rec1d1 interval
      have no mutation in exon sequence. The heterozygous rec1d1 interval in B6.lpr
      demonstrates exacerbated autoimmunity. For example, non-hematopoietic stem cell
      derived cells of the B6.Sle2c1rec1d1.lpr mice promote T-cell proliferation in
      vivo. These findings led us to conclude that the Skint6 variant in the rec1d1
      interval is the most likely causative gene of mouse lupus.

PMID- 28490807
TI  - Zeylenone, a naturally occurring cyclohexene oxide, inhibits proliferation and
      induces apoptosis in cervical carcinoma cells via PI3K/AKT/mTOR and MAPK/ERK
      pathways.
AB  - There is a strong rationale to therapeutically target the PI3K/Akt/mTOR and
      MAPK/ERK pathways in cervical carcinoma since they are highly deregulated in this
      disease. Previous study by our group have demonstrated that Zeylenone (Zey)
      exhibited strong suppressive activity on PI3K/AKT/mTOR and MAPK/ERK signaling,
      providing a foundation to investigate its antitumor activity in cervical
      carcinoma. Herein, the present study aimed to investigate suppressive effect of
      Zey on HeLa and CaSki cells, and further explore the underlying mechanisms. Cells
      were treated with Zey for indicated time, followed by measuring its effects on
      cell viability, colony formation, cell cycle, cell apoptosis, and signal
      pathways. In vivo antitumor activity of Zey was then assessed with nude
      xenografts. We found that Zey substantially suppressed cell proliferation,
      induced cell cycle arrest, and increased cell apoptosis, accompanied by increased
      production of ROS, decreased mitochondrial membrane potential, activated caspase
      apoptotic cascade, and attenuated PI3K/Akt/mTOR and MAPK/ERK pathways.
      Additionally, in vivo experiments showed that Zey exerted good antitumor efficacy
      against HeLa bearing mice models via decreasing levels of p-PI3K and p-ERK.
      Collectively, these data clearly demonstrated the antitumor activity of Zey in
      cervical carcinoma cells, which is most likely via the regulation of
      PI3K/Akt/mTOR and MAPK/ERK pathways.

PMID- 28490806
TI  - Quantification of blood-brain barrier permeability by dynamic contrast-enhanced
      NIRS.
AB  - The blood-brain barrier (BBB) is integral to maintaining a suitable
      microenvironment for neurons to function properly. Despite its importance, there
      are no bedside methods of assessing BBB disruption to help guide management of
      critical-care patients. The aim of this study was to demonstrate that dynamic
      contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) can quantify the
      permeability surface-area product (PS) of the BBB. Experiments were conducted in
      rats in which the BBB was opened by image-guided focused ultrasound. DCE-NIRS
      data were acquired with two dyes of different molecular weight, indocyanine green
      (ICG, 67 kDa) and 800CW carboxylate (IRDye, 1166 Da), and PS maps were generated
      by DCE computer tomography (CT) for comparison. Both dyes showed a strong
      correlation between measured PS values and sonication power (R2 = 0.95 and 0.92
      for ICG and IRDye respectively), and the PS values for IRDye were in good
      agreement with CT values obtained with a contrast agent of similar molecular
      weight. These proof-of-principle experiments demonstrate that DCE NIRS can
      quantify BBB permeability. The next step in translating this method to critical
      care practice will be to adapt depth sensitive methods to minimize the effects of
      scalp contamination on NIRS PS values.

PMID- 28490808
TI  - Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal
      Cell recruitment.
AB  - Orchestration of bone repair processes requires crosstalk between different cell
      populations, including immune cells and mesenchymal stem/stromal cells (MSC).
      Extracellular vesicles (EV) as mediators of these interactions remain vastly
      unexplored. Here, we aimed to determine the mechanism of MSC recruitment by
      Dendritic Cells (DC), hypothesising that it would be mediated by EV. Primary
      human DC-secreted EV (DC-EV), isolated by ultracentrifugation, were characterized
      for their size, morphology and protein markers, indicating an enrichment in
      exosomes. DC-EV were readily internalized by human bone marrow-derived MSC,
      without impacting significantly their proliferation or influencing their
      osteogenic/chondrogenic differentiation. Importantly, DC-EV significantly and
      dose-dependently promoted MSC recruitment across a transwell system and enhanced
      MSC migration in a microfluidic chemotaxis assay. DC-EV content was analysed by
      chemokine array, indicating the presence of chemotactic mediators. Osteopontin
      and matrix metalloproteinase-9 were confirmed inside EV. In summary, DC-EV are
      naturally loaded with chemoattractants and can contribute to cell recruitment,
      thus inspiring the development of new tissue regeneration strategies.

PMID- 28490809
TI  - Hepatic estrogen receptor alpha is critical for regulation of gluconeogenesis and
      lipid metabolism in males.
AB  - Impaired estrogens action is associated with features of the metabolic syndrome
      in animal models and humans. We sought to determine whether disruption of hepatic
      estrogens action in adult male mice could recapitulate aspects of the metabolic
      syndrome to understand the mechanistic basis for the phenotype. We found 17beta
      estradiol (E2) inhibited hepatic gluconeogenic genes such as phosphoenolpyruvate
      carboxykinase 1 (Pck-1) and glucose 6-phosphatase (G6Pase) and this effect was
      absent in mice lacking liver estrogen receptor alpha (Esr1) (LERKO mice). Male
      LERKO mice displayed elevated hepatic gluconeogenic activity and fasting
      hyperglycemia. We also observed increased liver lipid deposits and triglyceride
      levels in male LERKO mice, resulting from increased hepatic lipogenesis as
      reflected by increased mRNA levels of fatty acid synthase (Fas) and acetyl-CoA
      carboxylase (Acc1). ChIP assay demonstrated estradiol (E2) induced ESR1 binding
      to Pck-1, G6Pase, Fas and Acc1 promoters. Metabolic phenotyping demonstrated both
      basal metabolic rate and feeding were lower for the LERKO mice as compared to
      Controls. Furthermore, the respiratory exchange rate was significantly lower in
      LERKO mice than in Controls, suggesting an increase in lipid oxidation. Our data
      indicate that hepatic E2/ESR1 signaling plays a key role in the maintenance of
      gluconeogenesis and lipid metabolism in males.

PMID- 28490810
TI  - Establishment of induced pluripotent stem cells from normal B cells and inducing
      AID expression in their differentiation into hematopoietic progenitor cells.
AB  - B cell derived induced pluripotent stem cells (BiPSCs) were recently established
      from peripheral blood B cells by the simultaneous transfection of Yamanaka
      factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPalpha using a Sendai virus vector.
      Here, using a different method, we established BiPSCs with immunoglobulin heavy
      chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The
      critical points of our method are pre-stimulation of B cells with IL-21 and CD40
      ligand (CD40L), followed by consecutive transfection of highly concentrated
      Yamanaka factors using a retroviral vector. Following each transfection the cells
      were centrifuged onto a retronectin coated plate and the activated by IL-4, IL-2,
      and CD40L. Furthermore, we established BiPSCs (BiPSC-A) in which activation
      induced cytidine deaminase (AID) could be induced using the doxycycline
      controlled. Both the parental BiPSC and BiPSC-A showed the capability of
      differentiating into hematopoietic progenitor cells (HPCs) based on confirmation
      of CD34 expression and colony-formation from CD34-positive cells. The findings
      that BiPSC-A can differentiate into HPCs suggest that there is a possibility that
      induction of AID expression would result in chromosomal translocations in the
      process of differentiation from BiPSCs, and therefore that these BiPSCs could be
      useful in elucidating the tumor origin of abnormal B cells in myelomagenesis.

PMID- 28490811
TI  - High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51
      refractory or relapsed B acute lymphoblastic leukemia patients.
AB  - Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal
      outcome with current therapy. We treated 42 primary refractory/hematological
      relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM
      MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells.
      The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 * 105/kg
      and were eventually settled at 1 * 105/kg for the most recent 20 cases. 36/40
      (90%) evaluated R/R patients achieved complete remission (CR) or CR with
      incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-.
      All of the most recent 20 patients achieved CR/CRi. Most cases only experienced
      mild to moderate CRS. 8/51 cases had seizures that were relieved by early
      intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic
      hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median
      follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo
      HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 * 105/kg, is
      effective and safe for treating refractory or relapsed B-ALL, and subsequent allo
      HCT could further reduce the relapse rate.

PMID- 28490812
TI  - HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications.
AB  - Epigenetic signaling pathways are implicated in tumorigenesis and therefore
      histone deacetylases (HDACs) represent novel therapeutic targets for cancers,
      including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti
      MM activities, unfavorable side effects limit their clinical efficacy. Isoform-
      and/or class-selective HDAC inhibition offers the possibility to maintain
      clinical activity while avoiding adverse events attendant to broad non-selective
      HDAC inhibition. We have previously reported that HDAC3 inhibition, either by
      genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation.
      Here we show that knockdown of HDAC3, but not HDAC1 or HDAC2, as well as BG45,
      downregulate expression of DNA methyltransferase 1 (DNMT1) mediating MM cell
      proliferation. DNMT1 expression is regulated by c-Myc, and HDAC3 inhibition
      triggers degradation of c-Myc protein. Moreover, HDAC3 inhibition results in
      hyperacetylation of DNMT1, thereby reducing the stability of DNMT1 protein.
      Combined inhibition of HDAC3 and DNMT1 with BG45 and DNMT1 inhibitor 5
      azacytidine (AZA), respectively, triggers synergistic downregulation of DNMT1,
      growth inhibition and apoptosis in both MM cell lines and patient MM cells.
      Efficacy of this combination treatment is confirmed in a murine xenograft MM
      model. Our results therefore provide the rationale for combination treatment
      using HDAC3 inhibitor with DNMT1 inhibitor to improve patient outcome in MM.

PMID- 28490813
TI  - Leptin receptor antagonism of iNKT cell function: a novel strategy to combat
      multiple myeloma.
AB  - A hallmark of bone marrow changes with aging is the increase in adipocyte
      composition, but how this impacts development of multiple myeloma (MM) is
      unknown. Here, we report the role of the adipokine leptin as master regulator of
      anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT)
      cell function. A marked increase in serum leptin levels and leptin receptor (LR)
      expression on iNKT cells in MM patients and the 5T33 murine MM model was
      observed. MM cells and leptin synergistically counteracted anti-tumor
      functionality of both murine and human iNKT cells. In vivo blockade of LR
      signaling combined with iNKT stimulation resulted in superior anti-tumor
      protection. This was linked to persistent IFN-gamma secretion upon repeated iNKT
      cell stimulation and a restoration of the dynamic antigen-induced motility arrest
      as observed by intravital microscopy, thereby showing alleviation of iNKT cell
      anergy. Overall our data reveal the LR axis as novel therapeutic target for
      checkpoint inhibition to treat MM.

PMID- 28490814
TI  - Matrix elasticity-modified scaffold loaded with SDF-1alpha improves the in situ
      regeneration of segmental bone defect in rabbit radius.
AB  - The effectiveness of stem-cell based therapy has been hampered by the limited
      availability of stem cell sources, immune rejection, and difficulties in clinical
      adoption and regulatory approval. These obstacles can be partially circumvented
      by using in situ tissue engineering that recruits the endogenous stem/progenitor
      cells and provides cues to direct stem cell phenotype. Here, decellularized bone
      scaffold is mechanically modified by coating of collagen (Col)/hydroxyapatite
      (HA) mixture with optimal ratio and loaded with chemokine stromal cell-derived
      factor-1alpha (SDF-1alpha), in which endogenous stem cell recruitment can be
      improved by chemokine and stem cell fate can be regulated by matrix elasticity of
      the scaffold. This study shows that mesenchymal stem cells (MSCs) osteogenesis in
      vitro was enhanced by matrix elasticity and SDF-1alpha, and endogenous MSCs
      recruitment in subcutaneous implantation of rat was increased by the release of
      SDF-1alpha from the scaffold, and bone regeneration in rabbit large bone defect
      model was significantly improved by matrix elasticity and SDF-1alpha. In short,
      this study provides a new insight for developing novel engineered cell-free bone
      substitutes by mechanical modification for tissue engineering and regenerative
      medicine.

PMID- 28490815
TI  - Flexible and Self-Healing Aqueous Supercapacitors for Low Temperature
      Applications: Polyampholyte Gel Electrolytes with Biochar Electrodes.
AB  - A flexible and self-healing supercapacitor with high energy density in low
      temperature operation was fabricated using a combination of biochar-based
      composite electrodes and a polyampholyte hydrogel electrolyte. Polyampholytes, a
      novel class of tough hydrogel, provide self-healing ability and mechanical
      flexibility, as well as low temperature operation for the aqueous electrolyte.
      Biochar is a carbon material produced from the low-temperature pyrolysis of
      biological wastes; the incorporation of reduced graphene oxide conferred
      mechanical integrity and electrical conductivity and hence the electrodes are
      called biochar-reduced-graphene-oxide (BC-RGO) electrodes. The fabricated
      supercapacitor showed high energy density of 30 Wh/kg with ~90% capacitance
      retention after 5000 charge-discharge cycles at room temperature at a power
      density of 50 W/kg. At -30  degrees C, the supercapacitor exhibited an energy
      density of 10.5 Wh/kg at a power density of 500 W/kg. The mechanism of the low
      temperature performance excellence is likely to be associated with the concept of
      non-freezable water near the hydrophilic polymer chains, which can motivate
      future researches on the phase behaviour of water near polyampholyte chains. We
      conclude that the combination of the BC-RGO electrode and the polyampholyte
      hydrogel electrolyte is promising for supercapacitors for flexible electronics
      and for low temperature environments.

PMID- 28490816
TI  - Rethinking Sexual Citizenship.
AB  - Over the last two decades sexuality has emerged as a key theme in debates about
      citizenship, leading to the development of the concept of sexual citizenship.
      This article reviews this literature and identifies four main areas of critical
      framing: work that contests the significance of sexuality to citizenship;
      critiques that focus on the possibilities and limitations of mobilising the
      language of citizenship in sexual politics; analyses of sexual citizenship in
      relation to nationalisms and border making; and literature that critically
      examines western constructions of sexuality and sexual politics underpinning
      understandings of sexual citizenship. In order to progress the field
      theoretically, the article seeks to extend critiques of sexual citizenship
      focusing on two key aspects of its construction: the sexual citizen-subject and
      spaces of sexual citizenship. It argues for a critical rethink that encompasses a
      de-centring of a 'western-centric' focus in order to advance understandings of
      how sexual citizenship operates both in the Global North and South.

PMID- 28490817
TI  - Transphobic 'Honour'-Based Abuse: A Conceptual Tool.
AB  - This article proposes that an understanding of transphobic 'honour'-based abuse
      can be employed as a conceptual tool to explore trans people's experiences of
      familial abuse. This conception has evolved by connecting a sociology of shame,
      Goffman's work on stigma and 'honour'-based ideology. The discussion draws upon
      findings of a qualitative study which explored trans people's experiences of
      domestic violence and abuse. Narrative interviews were undertaken with 15 trans
      people who had either experienced abuse or whose perceptions were informed
      experientially through their support of others. Transcripts were analysed using
      the Listening Guide. Findings indicate that trans people can experience abuse as
      a result of a family's perceptions of shame and stigma. This article offers a
      novel way of conceptualising trans people's experiences of family-based abuse,
      but it also holds potential for understanding other relational contexts, for
      example, those of intimate partnerships.

PMID- 28490819
TI  - Testing Times: The Place of the Citizenship Test in the UK Immigration Regime and
      New Citizens' Responses to it.
AB  - Citizenship tests are designed to ensure that new citizens have the knowledge
      required for successful 'integration'. This article explores what those who have
      taken the test thought about its content. It argues that new citizens had high
      levels of awareness of debates about immigration and anti-immigration sentiment.
      Considering new citizens' views of the test, the article shows how many of them
      are aware of the role of the test in reassuring existing citizens of their
      fitness to be citizens. However, some new citizens contest this positioning in
      'acts of citizenship' where they assert claims to citizenship which are not
      necessarily those constructed by the state and implied in the tests. The article
      will argue that the tests and the nature of the knowledge required to pass them
      serve to retain new citizens in a position of less-than-equal citizenship which
      is at risk of being discursively (if less often legally) revoked.

PMID- 28490818
TI  - The Structural Invisibility of Outsiders: The Role of Migrant Labour in the Meat
      Processing Industry.
AB  - This article examines the role of migrant workers in meat-processing factories in
      the UK. Drawing on materials from mixed methods research in a number of case
      study towns across Wales, we explore the structural and spatial processes that
      position migrant workers as outsiders. While state policy and immigration
      controls are often presented as a way of protecting migrant workers from work
      based exploitation and ensuring jobs for British workers, our research highlights
      that the situation 'on the ground' is more complex. We argue that 'self
      exploitation' among the migrant workforce is linked to the strategies of
      employers and the organisation of work, and that hyper-flexible work patterns
      have reinforced the spatial and social invisibilities of migrant workers in this
      sector. While this creates problems for migrant workers, we conclude that it is
      beneficial to supermarkets looking to supply consumers with the regular supply of
      cheap food to which they have become accustomed.

PMID- 28490820
TI  - The End of Hypergamy: Global Trends and Implications.
AB  - The gender gap in education that has long favored men has reversed for young
      adults in almost all high and middle-income countries. In 2010, the proportion of
      women aged 25-29 with a college education was higher than that of men in more
      than 139 countries which altogether represent 86% of the world's population.
      According to recent population forecasts, women will have more education than men
      in nearly every country in the world by 2050, with the exception of only a few
      African and West Asian countries (KC et al. 2010). The reversal of the gender gap
      in education has major implications for the composition of marriage markets,
      assortative mating, gender equality, and marital outcomes such as divorce and
      childbearing (Van Bavel 2012). In this work, we focus on its implications for
      trends in assortative mating and, in particular, for educational hypergamy: the
      pattern in which husbands have more education than their wives. This represents a
      substantial update to previous studies (Esteve et al. 2012) in terms of the
      number of countries and years included in the analysis. We present findings from
      an almost comprehensive world-level analysis using census and survey microdata
      from 420 samples and 120 countries spanning from 1960 to 2011, which allow us to
      assert that the reversal of the gender gap in education is strongly associated
      with the end of hypergamy and increases in hypogamy (wives have more education
      that their husbands). We not only provide near universal evidence of this trend
      but extend our analysis to consider the implications of the end of hypergamy for
      family dynamics, outcomes and gender equality. We draw on European microdata to
      examine whether women are more likely to be the breadwinners when they marry men
      with lower education than themselves and discuss recent research regarding
      divorce risks among hypogamous couples. We close our analysis with an examination
      of attitudes about women earning more money than their husbands and about the
      implications for children when a woman works for pay.

PMID- 28490821
TI  - Who support open access publishing? Gender, discipline, seniority and other
      factors associated with academics' OA practice.
AB  - This paper presents the findings from a survey study of UK academics and their
      publishing behaviour. The aim of this study is to investigate academics'
      attitudes towards and practice of open access (OA) publishing. The results are
      based on a survey study of academics at 12 Russell Group universities, and
      reflect responses from over 1800 researchers. This study found that whilst most
      academics support the principle of making knowledge freely available to everyone,
      the use of OA publishing among UK academics was still limited despite relevant
      established OA policies. The results suggest that there were differences in the
      extent of OA practice between different universities, academic disciplines, age
      and seniorities. Academics' use in OA publishing was also related to their
      awareness of OA policy and OA repositories, their attitudes towards the
      importance of OA publishing and their belief in OA citation advantage. The
      implications of these findings are relevant to the development of strategies for
      the implementation of OA policies.

PMID- 28490822
TI  - How to reduce the number of rating scale items without predictability loss?
AB  - Rating scales are used to elicit data about qualitative entities (e.g., research
      collaboration). This study presents an innovative method for reducing the number
      of rating scale items without the predictability loss. The "area under the
      receiver operator curve method" (AUC ROC) is used. The presented method has
      reduced the number of rating scale items (variables) to 28.57% (from 21 to 6)
      making over 70% of collected data unnecessary. Results have been verified by two
      methods of analysis: Graded Response Model (GRM) and Confirmatory Factor Analysis
      (CFA). GRM revealed that the new method differentiates observations of high and
      middle scores. CFA proved that the reliability of the rating scale has not
      deteriorated by the scale item reduction. Both statistical analysis evidenced
      usefulness of the AUC ROC reduction method.

PMID- 28490823
TI  - International patent families: from application strategies to statistical
      indicators.
AB  - This paper provides an in-depth analysis of the characteristics of international
      patent families, including their domestic component. We exploit a relatively
      under-studied feature of patent families, namely the number of patents covering
      the same invention within a given jurisdiction. Using this information, we
      highlight common patterns in the structure of international patent families,
      which reflect both the patenting strategies of innovators and the peculiarities
      of the different patent systems. While the literature has extensively used family
      size, i.e. the number of countries in which a given invention is protected, as a
      measure of patent value, our results suggest that the number of patent filings in
      the priority country within a patent family as well as the timespan between the
      first and last filings within a family are other insightful indicators of the
      value of patented innovations.

PMID- 28490824
TI  - Patent information retrieval: approaching a method and analysing nanotechnology
      patent collaborations.
AB  - Many challenges still remain in the processing of explicit technological
      knowledge documents such as patents. Given the limitations and drawbacks of the
      existing approaches, this research sets out to develop an improved method for
      searching patent databases and extracting patent information to increase the
      efficiency and reliability of nanotechnology patent information retrieval process
      and to empirically analyse patent collaboration. A tech-mining method was applied
      and the subsequent analysis was performed using Thomson data analyser software.
      The findings show that nations such as Korea and Japan are highly collaborative
      in sharing technological knowledge across academic and corporate organisations
      within their national boundaries, and China presents, in some cases, a great
      illustration of effective patent collaboration and co-inventorship. This study
      also analyses key patent strengths by country, organisation and technology.

PMID- 28490825
TI  - Citation-based clustering of publications using CitNetExplorer and VOSviewer.
AB  - Clustering scientific publications in an important problem in bibliometric
      research. We demonstrate how two software tools, CitNetExplorer and VOSviewer,
      can be used to cluster publications and to analyze the resulting clustering
      solutions. CitNetExplorer is used to cluster a large set of publications in the
      field of astronomy and astrophysics. The publications are clustered based on
      direct citation relations. CitNetExplorer and VOSviewer are used together to
      analyze the resulting clustering solutions. Both tools use visualizations to
      support the analysis of the clustering solutions, with CitNetExplorer focusing on
      the analysis at the level of individual publications and VOSviewer focusing on
      the analysis at an aggregate level. The demonstration provided in this paper
      shows how a clustering of publications can be created and analyzed using freely
      available software tools. Using the approach presented in this paper,
      bibliometricians are able to carry out sophisticated cluster analyses without the
      need to have a deep knowledge of clustering techniques and without requiring
      advanced computer skills.

PMID- 28490826
TI  - Understanding and Assessing Word Comprehension.
AB  - The Intermodal Preferential Looking (IPL) task was developed to assess
      comprehension in infants and toddlers. We extend this methodology to examine word
      comprehension in preschool children using two measures: proportion of looking
      time to target (LTT) and longest look (LL) to target. Children (3-6 years) were
      tested with the IPL for comprehension of nouns, verbs, and adjectives. Both LTT
      and LL scores showed that, across all ages, eye gaze to the target word increased
      from baseline to test; there were higher scores for nouns compared to verbs and
      adjectives. We also compare IPL performance to scores on a standardized test of
      receptive vocabulary (PPVT-4). Correlations with PPVT-4 scores were stronger for
      LTT than LL measures. The IPL may provide an alternative method for assessing
      word comprehension in preschool children with behavioral limitations.

PMID- 28490828
TI  - Family Trajectories and Well-being of Children Born to Lone Mothers in the UK.
AB  - We investigate how lone mothers' heterogeneity in partnership trajectories is
      associated with children's well-being. We use data from the Millennium Cohort
      Study, which follows a large sample of children born in the UK in 2000-2002. We
      divide children who were born to lone mothers into four groups based on their
      mothers' partnership trajectories between birth and age seven, which cover more
      than 80% of these children's family experiences. We then analyse how these
      trajectories are associated with markers of health, cognitive and socio-emotional
      outcomes measured at around age seven. We find that compared to the children that
      live continuously with lone mothers, children whose biological father stably
      joined the household have better cognitive and socio-emotional outcomes. In
      contrast, children in trajectories characterised by living with a stepfather or
      who experienced biological father joining in the family followed by biological
      parents' dissolution had outcomes similar to children living continuously with
      lone mothers. The results underscore the importance of treating children born to
      lone mothers as a heterogeneous category.

PMID- 28490827
TI  - Sexual Risk Among African American Women: Psychological Factors and the Mediating
      Role of Social Skills.
AB  - Prior research demonstrates a positive association between mental health problems
      and sexual risk for African American women. Using the social skills deficit
      hypothesis, we proposed that social skills mediate this relationship. African
      American women (n = 557, M age = 20.58) completed measures of depression, stress,
      emotional dysregulation, sexual risk behaviors, and perceptions of their social
      skills with their primary sexual partner. Social skills mediated the link between
      the mental health assessments and a composite sexual risk index. Theoretical
      implications of extending the social skill deficit hypothesis are discussed as
      well as implications for interventions.

PMID- 28490829
TI  - Does Living in a Fatherless Household Compromise Educational Success? A
      Comparative Study of Cognitive and Non-cognitive Skills.
AB  - This study addresses the relationship between various family forms and the level
      of cognitive and non-cognitive skills among 15- to 16-year-old students. We
      measure cognitive skills using standardized scores in mathematics; non-cognitive
      abilities are captured by a composite measure of internal locus of control
      related to mathematics. A particular focus lies on father absence although we
      also examine the role played by co-residence with siblings and grandparents. We
      use cross-nationally comparable data on students participating in the Programme
      for International Student Assessment's release for 2012. By mapping inequalities
      by family forms across 33 developed countries, this study provides robust cross
      country comparable evidence on the relationship of household structure with both
      cognitive and non-cognitive skills. The study produces three key results: first,
      the absence of fathers from the household as well as co-residence with
      grandparents is associated with adverse outcomes for children in virtually all
      developed countries. Second, this is generally true in terms of both cognitive
      and non-cognitive skills, although the disadvantage connected to both family
      forms is notably stronger in the former than in the latter domain. Finally, there
      is marked cross-national diversity in the effects associated with the presence in
      the household of siblings and especially grandparents which furthermore differs
      across the two outcomes considered.

PMID- 28490830
TI  - Explaining Conflicting Results in Research on the Heterogeneous Effects of
      Parental Separation on Children's Educational Attainment According to Social
      Background.
AB  - In recent years, researchers have become increasingly interested in how the
      effects of parental separation on children's educational attainment vary with
      social background. On the one hand, parents with more resources might be better
      able to prevent possible adverse events like separation to affect their
      children's outcomes. On the other hand, children from higher social backgrounds
      might have more resources to lose from a parental separation. A wide range of
      empirical studies on the issue have come to inconsistent conclusions, with
      support found for both perspectives. The aim of this paper is to monitor the
      influence of methodological and operational choices on the different results
      observed across studies. We focus on aspects such as the operationalization of
      key variables, the measurement of inequality in absolute and relative terms and
      the different strategies used to address endogeneity. We study the effects of
      parental separation on educational attainment for a cohort of British children
      born in 1970 and find that conclusions change depending on whether social
      background is measured using the mother's or father's characteristics and whether
      relative or absolute differences between groups are considered. Results are
      relatively insensitive to the operationalization of dependent variables and the
      treatment of missing data. When using data from Understanding Society instead of
      the British Cohort Study, results also did not change. We reflect on how these
      findings can explain the contradictory results from earlier studies on the topic,
      and how heterogeneity in the effects of parental separation by socio-economic
      background should be interpreted.

PMID- 28490831
TI  - Parental Separation and School Performance Among Children of Immigrant Mothers in
      Sweden.
AB  - Immigration and family change are two demographic processes that have changed the
      face of European societies and are associated with inequalities in child
      outcomes. Yet there is little research outside the USA on whether the effects of
      family dynamics on children's life chances vary by immigrant background. We asked
      whether the effect of parental separation on educational achievement varies
      between immigrant backgrounds (ancestries) in Sweden. We used Swedish population
      register data on two birth cohorts (born in 1995 and 1996) of Swedish-born
      children and analyzed parental separation penalties on grade sums and non-passing
      grades (measured at ninth grade) across ten ancestry groups, defined by the
      mother's country of birth. We found that the parental separation effects vary
      across ancestries, being weakest among children with Chilean-born mothers and
      strongest among children with mothers born in Bosnia and Herzegovina. In general,
      the effects were weaker in groups in which parental separation was a more common
      experience.

PMID- 28490832
TI  - Gender Differences in Depressive Symptoms Among HIV-Positive Concordant and
      Discordant Heterosexual Couples in China.
AB  - HIV seropositive individuals and their heterosexual partners/spouses, either
      seropositive or seronegative, are facing several mental health challenges. The
      objective of this study was to examine gender differences in depressive symptoms
      among HIV-positive concordant and HIV-discordant couples. We identified
      heterosexual couples from participants of a randomized controlled trial conducted
      in Anhui province, China. A total of 265 couples, comprising 129 HIV+ male/HIV-
      female couples, 98 HIV- male/HIV+ female couples, and 38 HIV-positive concordant
      couples, were included in the analyses. We collected data using the computer
      assisted personal interview method. We used a linear mixed-effects regression
      model to assess whether gender differences in depressive symptoms varied across
      couple types. HIV-positive women reported a significantly higher level of
      depressive symptoms than their partners/spouses. HIV-positive women with HIV
      positive partners had higher depressive symptoms than those with HIV-negative
      partners, whereas HIV-positive men reported similar levels of depressive symptoms
      regardless of their partners' serostatus. Among the concordant couples, those
      with the highest annual family income showed the greatest gender differences in
      depressive symptoms. We suggest that family interventions should be gender- and
      couple-type specific and that mental health counseling is warranted not only for
      HIV-positive women but also for HIV-negative women in an HIV-affected
      relationship.

PMID- 28490833
TI  - ASSESSING THE RELATION BETWEEN FLEXIBILITY IN EMOTIONAL EXPRESSION AND SYMPTOMS
      OF ANXIETY AND DEPRESSION: THE ROLES OF CONTEXT SENSITIVITY AND FEEDBACK
      SENSITIVITY.
AB  - Expressive flexibility (EF), the ability to enhance and suppress emotional
      expressions, predicts decreases in anxiety and depression symptoms years later
      (Bonanno, Papa, Lalande, Westphal, & Coifman, 2004). Bonanno and Burton (2013)
      proposed that knowing the most appropriate strategy for a situation (context
      sensitivity; CS), and awareness of how well strategies are working (feedback
      sensitivity; FS), partially explain this effect. We conducted a conditional
      process analysis to test this theory. One hundred thirty-eight undergraduates
      completed a behavioral measure of EF and self-reported symptoms of anxiety and
      depression, CS, and FS over one month. CS moderated the effect of EF on one-month
      changes in symptoms of anxiety and depression (p = .03): EF only predicted
      decreased anxiety and depression symptoms among people low in CS. FS mediated the
      effect of EF (95% CI: -.10, -.01) on changes in anxiety and depression symptoms:
      higher baseline EF was associated with higher two-week FS, which predicted
      decreased one-month anxiety and depression symptoms. Results suggest EF and CS
      may be compensatory skills and FS may be necessary to experience the adaptive
      effects of emotion regulation flexibility.

PMID- 28490834
TI  - Human fatigue and the crash of the airship Italia.
AB  - The airship Italia, commanded by General Umberto Nobile, crashed during its
      return flight from the North Pole in 1928. The cause of the accident was never
      satisfactorily explained. We present evidence that the crash may have been
      fatigue-related. Nobile's memoirs indicate that at the time of the crash he had
      been awake for at least 72 h. Sleep deprivation impairs multiple aspects of
      cognitive functioning necessary for exploration missions. Just prior to the
      crash, Nobile made three command errors, all of which are of types associated
      with inadequate sleep. First, he ordered a release of lift gas when he should
      have restarted engines (an example of incorrect data synthesis, with
      deterioration of divergent thinking); second, he inappropriately ordered the ship
      above the cloud layer (a deficiency in the assessment of relative risks); and
      third, he remained above the cloud layer for a prolonged period of time (examples
      of attention to secondary problems, and calculation problems). We argue that as a
      result of these three errors, which would not be expected from such an
      experienced commander, there was no longer enough static lift to maintain level
      flight when the ship went below the cloud layer. Applying Circadian Performance
      Simulation Software to the sleep-wake patterns described by Nobile in his
      memoirs, we found that the predicted performance for someone awake as long as he
      had been is extremely low. This supports the historical evidence that human
      fatigue contributed to the crash of the Italia.

PMID- 28490835
TI  - From non-preemptive to preemptive scheduling using synchronization synthesis.
AB  - We present a computer-aided programming approach to concurrency. The approach
      allows programmers to program assuming a friendly, non-preemptive scheduler, and
      our synthesis procedure inserts synchronization to ensure that the final program
      works even with a preemptive scheduler. The correctness specification is
      implicit, inferred from the non-preemptive behavior. Let us consider sequences of
      calls that the program makes to an external interface. The specification requires
      that any such sequence produced under a preemptive scheduler should be included
      in the set of sequences produced under a non-preemptive scheduler. We guarantee
      that our synthesis does not introduce deadlocks and that the synchronization
      inserted is optimal w.r.t. a given objective function. The solution is based on a
      finitary abstraction, an algorithm for bounded language inclusion modulo an
      independence relation, and generation of a set of global constraints over
      synchronization placements. Each model of the global constraints set corresponds
      to a correctness-ensuring synchronization placement. The placement that is
      optimal w.r.t. the given objective function is chosen as the synchronization
      solution. We apply the approach to device-driver programming, where the driver
      threads call the software interface of the device and the API provided by the
      operating system. Our experiments demonstrate that our synthesis method is
      precise and efficient. The implicit specification helped us find one concurrency
      bug previously missed when model-checking using an explicit, user-provided
      specification. We implemented objective functions for coarse-grained and fine
      grained locking and observed that different synchronization placements are
      produced for our experiments, favoring a minimal number of synchronization
      operations or maximum concurrency, respectively.

PMID- 28490836
TI  - Prior Knowledge of Target Direction and Intended Movement Selection Improves
      Indirect Reaching Movement Decoding.
AB  - Objective. Previous studies have demonstrated that target direction information
      presented by the dorsal premotor cortex (PMd) during movement planning could be
      incorporated into neural decoder for achieving better decoding performance. It is
      still unknown whether the neural decoder combined with only target direction
      could work in more complex tasks where obstacles impeded direct reaching paths.
      Methods. In this study, spike activities were collected from the PMd of two
      monkeys when performing a delayed obstacle-avoidance task. We examined how target
      direction and intended movement selection were encoded in neuron population
      activities of the PMd during movement planning. The decoding performances of
      movement trajectory were compared for three neural decoders with no prior
      knowledge, or only target direction, or both target direction and intended
      movement selection integrated into a mixture of trajectory model (MTM). Results.
      We found that not only target direction but also intended movement selection was
      presented in neural activities of the PMd during movement planning. It was
      further confirmed by quantitative analysis. Combined with prior knowledge, the
      trajectory decoder achieved the best performance among three decoders.
      Conclusion. Recruiting prior knowledge about target direction and intended
      movement selection extracted from the PMd could enhance the decoding performance
      of hand trajectory in indirect reaching movement.

PMID- 28490837
TI  - Transcriptional Profiling at High Temporal Resolution Reveals Robust
      Immune/Inflammatory Responses during Rat Sciatic Nerve Recovery.
AB  - After peripheral nerve injury, immune/inflammatory responses are triggered, which
      are critical for nerve regeneration. Despite their importance, the underlying
      molecular changes in immune/inflammatory responses remain largely unknown. In
      this study, we systematically analyzed differentially expressed genes in
      immune/inflammatory-related pathways at high temporal resolution and
      experimentally validated gene expression changes with RT-PCR following sciatic
      nerve crush in rats. We found that immune/inflammatory reactions not only occur
      in the acute injury but also remained activated over two weeks after injury.
      Detailed bioinformatic studies suggested that multiple immune/inflammatory
      pathways, including agranulocyte adhesion and diapedesis, granulocyte adhesion
      and diapedesis, IL-6 signaling, and IL-10 signaling, were sustained activated
      during nerve degeneration and regeneration. Our current study expands our
      understanding of the molecular basis of altered immune/inflammatory-related
      pathways following injury and thus might offer the possibility of targeting
      related molecules as therapeutic intervention for peripheral nerve regeneration.

PMID- 28490839
TI  - Higher-Order Chromatin Regulation of Inflammatory Gene Expression.
AB  - Whether it is caused by viruses and bacteria infection, or low-grade chronic
      inflammation of atherosclerosis and cellular senescence, the transcription factor
      (TF) NF-kappaB plays a central role in the inducible expression of inflammatory
      genes. Accumulated evidence has indicated that the chromatin environment is the
      main determinant of TF binding in gene expression regulation, including the
      stimulus-responsive NF-kappaB. Dynamic changes in intra- and interchromosomes are
      the key regulatory mechanisms promoting the binding of TFs. When an inflammatory
      process is triggered, NF-kappaB binds to enhancers or superenhancers, triggering
      the transcription of enhancer RNA (eRNA), driving the chromatin of the NF-kappaB
      binding gene locus to construct transcriptional factories, and forming intra- or
      interchromosomal contacts. These processes reveal a mechanism in which
      intrachromosomal contacts appear to be cis-control enhancer-promoter
      communications, whereas interchromosomal regulatory elements construct trans-form
      relationships with genes on other chromosomes. This article will review emerging
      evidence on the genome organization hierarchy underlying the inflammatory
      response.

PMID- 28490841
TI  - Unraveling Sugar Chain Signatures of the "Seeds" of Tumor Metastasis.

PMID- 28490840
TI  - Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice.
AB  - Aim. Inflammation is important in heart failure (HF). The role of the immune
      receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated
      in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model
      caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a
      KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte
      SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6
      weeks, cardiac functions and dimensions were analyzed by echocardiography and
      heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced
      survival compared to SERC2a KO mice, with a median life expectancy of 58 days
      compared to 63 days. Both HF groups displayed increased left atrium size, lung
      weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis.
      However, there were no significant differences between the groups. Conclusion. In
      mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median
      life expectancy. The cause remains elusive, as all investigated HF parameters
      were unaltered. Still, these findings support a salutary role of TLR9 in some
      subsets of HF conditions and underline the importance for future studies on the
      mechanisms of TLR9 in diastolic HF.

PMID- 28490838
TI  - Adipokine Contribution to the Pathogenesis of Osteoarthritis.
AB  - Recent studies have shown that overweight and obesity play an important role in
      the development of osteoarthritis (OA). However, joint overload is not the only
      risk factor in this disease. For instance, the presence of OA in non-weight
      bearing joints such as the hand suggests that metabolic factors may also
      contribute to its pathogenesis. Recently, white adipose tissue (WAT) has been
      recognized not only as an energy reservoir but also as an important secretory
      organ of adipokines. In this regard, adipokines have been closely associated with
      obesity and also play an important role in bone and cartilage homeostasis.
      Furthermore, drugs such as rosuvastatin or rosiglitazone have demonstrated
      chondroprotective and anti-inflammatory effects in cartilage explants from
      patients with OA. Thus, it seems that adipokines are important factors linking
      obesity, adiposity, and inflammation in OA. In this review, we are focused on
      establishing the physiological mechanisms of adipokines on cartilage homeostasis
      and evaluating their role in the pathophysiology of OA based on evidence derived
      from experimental research as well as from clinical-epidemiological studies.

PMID- 28490842
TI  - The need for virtual reality simulators in dental education: A review.
AB  - Virtual reality simulators are becoming an essential part of modern education.
      The benefits of Virtual reality in dentistry is constantly being assessed as a
      method or an adjunct to improve fine motor skills, hand-eye coordination in pre
      clinical settings and overcome the monetary and intellectual challenges involved
      with such training. This article, while providing an overview of the virtual
      reality dental simulators, also looks at the link between virtual reality
      simulation and current pedagogical knowledge.

PMID- 28490844
TI  - Attitudes of dental professional staff and auxiliaries in Riyadh, Saudi Arabia,
      toward disclosure of medical errors.
AB  - AIM: To collect empirical data on the attitudes of dental professionals and
      dental auxiliaries in Riyadh, Saudi Arabia, regarding the disclosure of medical
      errors. METHODS: A cross-sectional study was conducted, involving the
      administration of a questionnaire to a sample of 586 participants recruited from
      over 10 government and private dental institutions in Riyadh between August 2015
      and January 2016. The questionnaire collected information regarding participant
      opinions on (a) personal beliefs, norms, and practices regarding medical errors,
      (b) the nature of errors that should be disclosed, and (c) who should disclose
      errors. RESULTS: Most (94.4%) participants preferred that medical errors should
      be disclosed. However, personal preferences, perceptions of the norm and current
      practices with respect to which type (seriousness) of error should be disclosed
      were inconsistent. Only 17.9% of participants perceived that it was the current
      practice to disclose errors resulting in "Major harm". Over 68% of respondents
      reported a personal belief, a perception of the norm and a perception of current
      practice that errors should be disclosed by the erring dentist. Participants at
      government institutions were more likely to disclose errors than those at private
      institutions. There were also significant differences in the responses with
      respect to gender, age, and nationality. The implications for the development of
      guidelines to help Saudi dentists adopt ethical courses of action for the
      disclosure of errors are considered. CONCLUSIONS: (1) The majority of
      participants personally believed that errors should be disclosed, (2) there was
      little agreement between participant personal beliefs and perceptions of the norm
      and practice with respect to which type of errors should be disclosed, (3) there
      was strong agreement that the erring dentist is responsible for reporting errors,
      and (4) the attitudes of the participants varied with respect to type of
      institution, age, gender, and nationality.

PMID- 28490843
TI  - Factors affecting polymerization of resin-based composites: A literature review.
AB  - AIM: The aim of this review was to help clinicians improve their understanding of
      the polymerization process for resin-based composites (RBC), the effects of
      different factors on the process and the way in which, when controlled, the
      process leads to adequately cured RBC restorations. METHODS: Ten factors and
      their possible effects on RBC polymerization are reviewed and discussed, with
      some recommendations to improve that process. These factors include RBC shades,
      their light curing duration, increment thickness, light unit system used, cavity
      diameter, cavity location, light curing tip distance from the curing RBC surface,
      substrate through which the light is cured, filler type, and resin/oral cavity
      temperature. CONCLUSION: The results of the review will guide clinicians toward
      the best means of providing their patients with successfully cured RBC
      restorations.

PMID- 28490845
TI  - A survey of pediatric dentists' caries-related treatment decisions and
      restorative modalities - A web-based survey.
AB  - OBJECTIVE: To identify current practices and the preferred caries-related
      treatment decisions and restorative modalities of primary teeth among pediatric
      dental practitioners in Saudi Arabia. MATERIALS AND METHODS: This was a web-based
      cross-sectional survey conducted among licensed pediatric dental practitioners in
      Saudi Arabia. Following the retrieval of the email addresses from the Saudi
      Dental Council, an email explaining the purpose of the study and a link to
      SurveyMonkey electronic survey consisting of 23 questions was sent to all the
      members registered under the pediatric dentistry practitioners, starting in
      September till December 2013. The data obtained was analyzed using descriptive
      statistics and chi square with and without tabulation processes. The level of
      significance was set at p < 0.05. RESULTS: A total of 108 [54 (50%) male and 54
      (50%) female] pediatric dental practitioners responded to the survey out of 308
      targeted individuals for an overall response rate of 35.1%. About 65% of the
      respondents reported that they have never considered pre-veneered or Zirconia
      crowns as a restorative option for carious vital anterior primary teeth. About
      40% reported doing pulpectomy and restored with composite strip crowns at all
      times. About 86% of the respondents reported doing pulpotomy and stainless steel
      crown for restoring carious vital posterior primary teeth whereas 73.8% reported
      restoring with composite resin. However, 83.1% of the respondents reported that
      they never used pre-veneered or Zirconia crowns after pulpotomy for restoring
      carious vital posterior primary teeth. A significantly higher number of male
      participants reported that they used esthetic pediatric crowns in their practice
      compared to female participants (p < 0.001). CONCLUSION: The prevalence of use of
      composite resin to restore primary teeth was higher compared to glass ionomer
      cements and amalgam whereas a limited use of esthetic pediatric crowns was found
      among the sample surveyed. Esthetic pediatric crowns were more utilized by male
      compared to female participants.

PMID- 28490846
TI  - Reliability of intra-oral camera using teledentistry in screening of oral
      diseases - Pilot study.
AB  - OBJECTIVE: Reliability of intra-oral camera using teledentistry in screening of
      oral diseases. METHODOLOGY: A trained and calibrated examiner used intra-oral
      camera to capture videos of oral cavity along with clinical examination to
      evaluate caries, plaque, calculus, tooth wear and fluorosis, stains in children.
      RESULTS: The mean DT and DMFT were significantly higher with use of intra-oral
      camera than with clinical examination (p = 0.001 and 0.001) respectively. A
      positive strong significant correlation was seen between intra-oral camera and
      clinical examination with respect to DT, MT, FT and DMFT (r = 0.721, p < 0.001; r
      = 0.908, p < 0.001; r = 0.869, p < 0.001; r = 0.876, p < 0.001) respectively.
      Reliability of intra-oral camera when compared with clinical examination varied
      from substantial to almost perfect agreement various oral conditions. Disclosed
      immature plaque was not clear while mature plaque was clearly demonstrated.
      CONCLUSION/RECOMMENDATIONS: Intra-oral camera was shown to be a reliable tool to
      identify common oral diseases. Further studies involving applications like
      sealant retention, pre-malignant lesions, recurrent apthae, gingival recession
      and dental malocclusion and effectiveness in regular screening are needed.

PMID- 28490847
TI  - Sexual dimorphism, pattern of third molar and mandibular second premolar agenesis
      in Indian paediatric orthodontic patients.
AB  - OBJECTIVE: To determine and compare the prevalence and pattern of agenesis of
      third molar and mandibular second premolar in paediatric orthodontic patients of
      age group 9-15 for sexual dimorphism. METHODS: The digital orthopantograph was
      obtained from the archive record of patients of age group 9-15 year. Radiographs
      of 301 patients were evaluated after taking exclusion criteria into account and
      were assessed for the presence/absence of third molars and mandibular second
      premolar. Tooth development evaluation followed the method of Demirjian et al.,
      based on eight stages of tooth formation. The agenesis of third molar in maxilla
      and mandible between age groups and gender was compared using Chi-squared test.
      RESULTS: The rate of agenesis of third molars was observed 36.8% in the present
      study. Twenty-four (24.3%) percentage of the study population showed agenesis of
      all the four third molars. The agenesis of third molars was found to be higher
      among males than females (p > 0.05). Prevalence of agenesis of mandibular second
      premolar was 4.7-5%. CONCLUSIONS: Agenesis of third molars was more commonly seen
      in the maxilla, having male predilection. Maxillary right third molar was the
      most commonly missing tooth irrespective of gender.

PMID- 28490848
TI  - Precise large deviations of aggregate claims in a size-dependent renewal risk
      model with stopping time claim-number process.
AB  - In this paper, we consider a size-dependent renewal risk model with stopping time
      claim-number process. In this model, we do not make any assumption on the
      dependence structure of claim sizes and inter-arrival times. We study large
      deviations of the aggregate amount of claims. For the subexponential heavy-tailed
      case, we obtain a precise large-deviation formula; our method substantially
      relies on a martingale for the structure of our models.

PMID- 28490849
TI  - A Hilbert-type fractal integral inequality and its applications.
AB  - By using thefractal theory and the methods of weight function, a Hilbert-type
      fractal integral inequality and its equivalent form are given. Their constant
      factors are proved being the best possible, and their applications are discussed
      briefly.

PMID- 28490850
TI  - A new Z-eigenvalue localization set for tensors.
AB  - A new Z-eigenvalue localization set for tensors is given and proved to be tighter
      than those in the work of Wang et al. (Discrete Contin. Dyn. Syst., Ser. B
      22(1):187-198, 2017). Based on this set, a sharper upper bound for the Z-spectral
      radius of weakly symmetric nonnegative tensors is obtained. Finally, numerical
      examples are given to verify the theoretical results.

PMID- 28490851
TI  - New applications of the existence of solutions for equilibrium equations with
      Neumann type boundary condition.
AB  - Using the existence of solutions for equilibrium equations with a Neumann type
      boundary condition as developed by Shi and Liao (J. Inequal. Appl. 2015:363,
      2015), we obtain the Riesz integral representation for continuous linear maps
      associated with additive set-valued maps with values in the set of all closed
      bounded convex non-empty subsets of any Banach space, which are generalizations
      of integral representations for harmonic functions proved by Leng, Xu and Zhao
      (Comput. Math. Appl. 66:1-18, 2013). We also deduce the Riesz integral
      representation for set-valued maps, for the vector-valued maps of Diestel-Uhl and
      for the scalar-valued maps of Dunford-Schwartz.

PMID- 28490852
TI  - Where Are the Beds? Housing Locations for Transition Age Youth Exiting Public
      Systems.
AB  - Transition age youth (TAY) from the child welfare and juvenile justice systems
      experience high rates of homelessness, but little is known about the
      neighborhoods to which they return after they exit these systems. This
      exploratory study investigates whether housing options are located in areas where
      TAY exit public systems and if the characteristics of areas surrounding these
      facilities support their transition to adulthood. Results show that housing is
      not related to areas where TAY exit public systems. Further, supportive housing
      and shelter density is related to low-income areas. Implications for practice and
      policy on housing locations for TAY are discussed.

PMID- 28490853
TI  - Team Learning: New Insights Through a Temporal Lens.
AB  - Team learning is a complex social phenomenon that develops and changes over time.
      Hence, to promote understanding of the fine-grained dynamics of team learning,
      research should account for the temporal patterns of team learning behavior.
      Taking important steps in this direction, this special issue offers novel
      insights into the dynamics of team learning by advocating a temporal perspective.
      Based on a symposium presented at the 2016 Interdisciplinary Network for Group
      Research (INGRoup) Conference in Helsinki, the four empirical articles in this
      special issue showcase four different and innovative approaches to implementing a
      temporal perspective in team learning research. Specifically, the contributions
      highlight team learning dynamics in student teams, self-managing teams, teacher
      teams, and command and control teams. The articles cover a broad range of methods
      and designs, including both qualitative and quantitative methodologies, and
      longitudinal as well as micro-temporal approaches. The contributors represent
      four countries and five different disciplines in group research.

PMID- 28490854
TI  - Effects of Sequences of Cognitions on Group Performance Over Time.
AB  - Extending past research showing that sequences of low cognitions (low-level
      processing of information) and high cognitions (high-level processing of
      information through questions and elaborations) influence the likelihoods of
      subsequent high and low cognitions, this study examines whether sequences of
      cognitions are related to group performance over time; 54 primary school students
      (18 triads) discussed and wrote an essay about living in another country (32,375
      turns of talk). Content analysis and statistical discourse analysis showed that
      within each lesson, groups with more low cognitions or more sequences of low
      cognition followed by high cognition added more essay words. Groups with more
      high cognitions, sequences of low cognition followed by low cognition, or
      sequences of high cognition followed by an action followed by low cognition,
      showed different words and sequences, suggestive of new ideas. The links between
      cognition sequences and group performance over time can inform facilitation and
      assessment of student discussions.

PMID- 28490855
TI  - Using Transactivity to Understand Emergence of Team Learning.
AB  - Team learning is a recurrent topic in research on effective teamwork. However,
      research about the fact that team learning processes emerge from conversations
      and the different forms this emergence can take is limited. The aim of this study
      is to determine whether the extent to which team members act on each other's
      reasoning (transactivity) can be used to understand how team learning processes
      emerge. Research on teacher teams was used as the case study: Video recordings of
      three different teacher teams were used as primary data, and the data were
      analyzed using qualitative interaction analysis. The analysis shows that the
      content of team learning processes changes when team members act more closely on
      each other's reasoning. In particular, team learning processes related to the
      storage and retrieval of information took place only in sequences in which team
      members acted closely on each other's reasoning.

PMID- 28490856
TI  - Team Leader Structuring for Team Effectiveness and Team Learning in Command-and
      Control Teams.
AB  - Due to their crucial and highly consequential task, it is of utmost importance to
      understand the levers leading to effectiveness of multidisciplinary emergency
      management command-and-control (EMCC) teams. We argue that the formal EMCC team
      leader needs to initiate structure in the team meetings to support organizing the
      work as well as facilitate team learning, especially the team learning process of
      constructive conflict. In a sample of 17 EMCC teams performing a realistic EMCC
      exercise, including one or two team meetings (28 in sum), we coded the team
      leader's verbal structuring behaviors (1,704 events), rated constructive conflict
      by external experts, and rated team effectiveness by field experts. Results show
      that leaders of effective teams use structuring behaviors more often (except
      asking procedural questions) but decreasingly over time. They support
      constructive conflict by clarifying and by making summaries that conclude in a
      command or decision in a decreasing frequency over time.

PMID- 28490857
TI  - Effects of the Caregiver Interaction Profile Training on Caregiver-Child
      Interactions in Dutch Child Care Centers: A Randomized Controlled Trial.
AB  - BACKGROUND: Previous studies underscore the need to improve caregiver-child
      interactions in early child care centers. OBJECTIVE: In this study we used a
      randomized controlled trial to examine whether a 5-week video feedback training
      can improve six key interactive skills of caregivers in early child care centers:
      Sensitive responsiveness, respect for autonomy, structuring and limit setting,
      verbal communication, developmental stimulation, and fostering positive peer
      interactions. METHOD: A total of 139 caregivers from 68 early child care groups
      for 0- to 4-year-old children in Dutch child care centers participated in this
      RCT, 69 in the intervention condition and 70 in the control condition. Caregiver
      interactive skills during everyday interactions with the children were rated from
      videotape using the Caregiver Interaction Profile (CIP) scales at pretest,
      posttest, and follow-up 3 months after the posttest. RESULTS: Results at posttest
      indicate a significant positive training effect on all six caregiver interactive
      skills. Effect sizes of the CIP training range between d = 0.35 and d = 0.79.
      Three months after the posttest, caregivers in the intervention group still
      scored significantly higher on sensitive responsiveness, respect for autonomy,
      verbal communication, and fostering positive peer interactions than caregivers in
      the control group with effect sizes ranging between d = 0.47 and d = 0.70.
      CONCLUSIONS: This study shows that the quality of caregiver-child interactions
      can be improved for all six important caregiver skills, with a relatively short
      training program. Possible ways to further improve the training and to implement
      it in practice and education are discussed.

PMID- 28490858
TI  - Social Network Size and Cognitive Functioning in Middle-Aged Adults: Cross
      Sectional and Longitudinal Associations.
AB  - The objective of the present study was to examine relations between social
      network size and three cognitive abilities (episodic memory, semantic memory,
      visuospatial ability) in middle-aged adults. We analyzed cross-sectional data on
      social network size and cognitive functioning that were available for 804
      participants aged 40-60 years. In addition, we examined 5- and 10-year follow-up
      measurements of cognitive functioning that were available for 604 and 255
      participants, respectively. Cross-sectional analyses revealed a positive
      association between social network size and each of the three cognitive
      abilities. Baseline network size was positively related to 5-year changes in
      semantic memory, and to 10-year changes in semantic as well as episodic memory,
      but was unrelated to changes in visuospatial performance. A minor portion of the
      sample (n = 131) had 10-year follow-up data on network size. Cross-lagged panel
      correlations revealed that baseline network size was associated with follow-up
      measurement in cognitive functioning (episodic memory, semantic memory), whereas
      baseline cognitive performance was unrelated to future network size. Together,
      the results demonstrate a small but positive relation between network size and
      declarative memory abilities, in line with models proposing a cognitive reserve
      built up by factors such as the increased cognitive stimulation associated with a
      more extensive social network.

PMID- 28490859
TI  - Blood is Thicker Than Water: Geography and the Dispersal of Family
      Characteristics Across the Globe.
AB  - This article introduces a new dataset of historical family characteristics based
      on ethnographic literature. The novelty of the dataset lies in the fact that it
      is constructed at the level of the ethnic group. To test the possibilities of the
      dataset, we construct a measure of family constraints on women's agency from it
      and explore its correlation to a number of geographical factors.

PMID- 28490860
TI  - Choroidal structure determined by binarizing optical coherence tomography images
      in eyes with reticular pseudodrusen.
AB  - PURPOSE: To compare the choroidal structure beneath the macular area in eyes with
      reticular pseudodrusen (RPD) and age-matched controls. METHODS: This study was
      performed at Nara Medical University Hospital, Japan. Twenty eyes of 14 patients
      (82.3+/-4.2 years, mean +/- standard deviation) with RPD and 35 eyes of 20 age
      matched controls (81.5+/-6.0 years) were studied. The choroidal structure was
      determined by binarizing the images obtained by enhanced depth imaging optical
      coherence tomography in all patients and controls. The total, luminal, and
      stromal choroidal areas were quantified by the binarization method. RESULTS: The
      total choroidal area of the eyes with RPD was significantly smaller than that of
      control eyes (P=0.001, unpaired t-test). Both the luminal and stromal areas in
      eyes with RPD were significantly smaller than that of control eyes (P=0.001,
      paired t-test), but there was no significant difference in the luminal/stromal
      ratio between eyes with RPD and control eyes. CONCLUSION: The total, luminal, and
      stromal choroidal areas in eyes with RPD were smaller than those of the control
      eyes. The reduction of the choroidal luminal and stromal areas may be due to a
      loss of the oxygen demand of the choroid due to RPE dysfunction.

PMID- 28490861
TI  - Efficacy of intravitreal aflibercept injections for Japanese patients with
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate the efficacy of intravitreal aflibercept therapy in
      treatment-naive Japanese patients with polypoidal choroidal vasculopathy (PCV)
      using Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. SUBJECTS
      AND METHODS: This study was a prospective, nonrandomized, interventional
      exploratory clinical trial performed in an institutional setting. Patients with
      PCV were treated with intravitreal aflibercept 2 mg/0.05 mL every 2 months after
      3 initial monthly doses, for 1 year. Visual acuity test using the ETDRS chart and
      indocyanine green angiography was performed at baseline and at 6 and 12 months
      after initiating the treatment, in addition to routine examinations performed at
      each visit. The main outcome measure was the proportion of patients who achieved
      <15 ETDRS letter score loss. RESULTS: Twenty-two patients were enrolled in this
      study. Nineteen (86%) patients were eligible for analysis. All the patients
      maintained their visual acuity (<15 ETDRS letter score loss) at 12 months. The
      ETDRS letter scores were 64.1 at baseline and 69.8 at 12 months (P<0.039). The
      polyps regressed completely in 14 (74%) patients at 12 months. Cataract
      progressed in 1 eye, but this progression was considered to be a senile change.
      CONCLUSIONS: Japanese patients with treatment-naive PCV, who were treated with
      intravitreal aflibercept every 2 months after 3 initial monthly doses, exhibited
      a significant increase in ETDRS letter scores and a high rate of polyp resolution
      at 12 months.

PMID- 28490862
TI  - Ultra-wide-field fluorescein angiography in diabetic retinopathy: a narrative
      review.
AB  - Fluorescein angiography (FA) is a useful examination in patients suffering from
      diabetic retinopathy (DR). Traditional angiograms explore 30 degrees -50 degrees 
      of the retina at once; however, visualization of peripheral retina is fundamental
      in order to assess nonperfused areas, vascular leakage, microvascular
      abnormalities, and neovascularizations. In order to expand the field of view,
      wide-field and ultra-wide-field imaging has been developed allowing to image up
      to 200 degrees  of retinal surface in one single shot. The aim of this narrative
      review was to provide an overview of the role of the most recent technique of
      ultra-wide-field fluorescein angiography in DR.

PMID- 28490864
TI  - Adherence to tobramycin inhaled powder vs inhaled solution in patients with
      cystic fibrosis: analysis of US insurance claims data.
AB  - PURPOSE: Tobramycin inhalation powder (TIP), the first dry-powder inhaled
      antibiotic for pulmonary Pseudomonas aeruginosa infection, is associated with
      reduced treatment burden, increased patient satisfaction, and higher self
      reported adherence for cystic fibrosis (CF) patients. We compared adherence in CF
      patients newly treated with TIP with those newly treated with the traditional
      tobramycin inhalation solution (TIS), using US insurance claims data. PATIENTS
      AND METHODS: From the Truven MarketScan(r) database, we identified CF patients
      chronically infected with P. aeruginosa who had been prescribed TIP between May
      1, 2013 to December 31, 2014, or TIS between September 1, 2010 to April 30, 2012
      with at least 12 months of continuous medical and pharmacy benefits prior to and
      following prescription. TIP and TIS adherence levels were assessed. RESULTS: A
      total of 145 eligible patients were identified for the TIP cohort and 306 for the
      TIS cohort. Significant differences in age distribution (25.0 vs 21.9 years for
      TIP vs TIS, respectively, P=0.017), type of health plan (P=0.014), employment
      status (72.4% vs 63.4% of TIP vs TIS patients in full-time employment, P=0.008),
      and some comorbidities were observed between the two cohorts. Although a
      univariate analysis found no significant differences between TIP and TIS (odds
      ratio [OR] 1.411, 95% confidence interval [CI] 0.949-2.098), TIP was moderately
      associated with higher adherence levels compared with TIS in a multivariable
      analysis, once various demographic and clinical characteristics were adjusted
      for. These included geographic location (OR: 1.566, CI: 1.016-2.413) and certain
      comorbidities. CONCLUSION: This study of US patient data supports previous
      findings that TIP is associated with better adherence compared with TIS; however,
      further studies will be required to fully elucidate differences in adherence
      between TIP and TIS.

PMID- 28490863
TI  - Development and evaluation of a new modular nanotransporter for drug delivery
      into nuclei of pathological cells expressing folate receptors.
AB  - PURPOSE: Modular nanotransporters (MNTs) are artificial multifunctional systems
      designed to facilitate receptor-specific transport from the cell surface into the
      cell nucleus through inclusion of polypeptide domains for accomplishing receptor
      binding and internalization, as well as sequential endosomal escape and nuclear
      translocation. The objective of this study was to develop a new MNT targeted at
      folate receptors (FRs) for precise delivery of therapeutic cargo to the nuclei of
      FR-positive cells and to evaluate its potential, particularly for delivery of
      therapeutic agents (eg, the Auger electron emitter 111In) into the nuclei of
      target cancer cells. METHODS: A FR-targeted MNT was developed by site-specific
      derivatization of ligand-free MNT with maleimide-polyethylene glycol-folic acid.
      The ability of FR-targeted MNT to accumulate in target FR-expressing cells was
      evaluated using flow cytometry, and intracellular localization of this MNT was
      assessed using confocal laser scanning microscopy of cells. The cytotoxicity of
      the 111In-labeled FR-targeted MNT was evaluated on HeLa and U87MG cancer cell
      lines expressing FR. In vivo micro-single-photon emission computed tomography/CT
      imaging and antitumor efficacy studies were performed with intratumoral injection
      of 111In-labeled FR-targeted MNT in HeLa xenograft-bearing mice. RESULTS: The
      resulting FR-targeted MNT accumulated in FR-positive HeLa cancer cell lines
      specifically and demonstrated the ability to reach its target destination - the
      cell nuclei. 111In-labeled FR-targeted MNT demonstrated efficient and specific FR
      positive cancer cell eradication. A HeLa xenograft in vivo model revealed
      prolonged retention of 111In delivered by FR-targeted MNT and significant tumor
      growth delay (up to 80% growth inhibition). CONCLUSION: The FR-targeted MNT met
      expectations of its ability to deliver active cargo into the nuclei of target FR
      positive cells efficiently and specifically. As a result of this finding the new
      FR-targeted MNT approach warrants broad evaluation.

PMID- 28490865
TI  - Poor 1st-year adherence to anti-osteoporotic therapy increases the risk of
      mortality in patients with magnetic resonance imaging-proven acute osteoporotic
      vertebral fractures.
AB  - AIM: Anti-osteoporotic therapy requires years of proper compliance to reduce the
      risk of fractures. This study investigated the effects of 1st-year adherence to
      anti-osteoporotic treatment on the risk of mortality in patients with magnetic
      resonance imaging-proven acute osteoporotic vertebral fractures after
      vertebroplasty. PATIENTS AND METHODS: This retrospective study included 294
      patients (252 females; mean age, 73.93+/-7.18 years) with osteoporosis and acute
      vertebral fractures treated with vertebroplasty between January 2001 and December
      2007. Sex, age, body mass index, comorbidities, previous hip fracture, number of
      vertebral fractures, 5-year re-fracture rate, and use of anti-osteoporotic
      therapy were recorded for each patient. Adherence was determined according to
      compliance and persistence for 1 year. Compliance was calculated as the
      medication possession ratio (MPR), and persistence as the time from treatment
      initiation to discontinuation. Poor adherence was defined as either non
      compliance or non-persistence. RESULTS: The MPR of the patients at 1 year was
      55.1%, with a persistence rate of 69.4% and a poor adherence rate of 62.6%. Cox
      regression analysis revealed that poor adherence to medications was associated
      with a significantly higher risk of mortality after adjustment for potential
      confounders (hazard ratio [HR]: 1.75; 95% CI: 1.13-2.71). Poor adherence to
      medications was significantly associated with an increase in the rate of
      infection (HR: 4.56; 95% CI: 1.12-18.52), which was the most common cause of
      death. CONCLUSION: Poor adherence to anti-osteoporotic therapy significantly
      increases the risk of morality, possibly due to an increased risk of infection.
      Efforts should be made to improve adherence.

PMID- 28490866
TI  - Nonpharmacological interventions to treat physical frailty and sarcopenia in
      older patients: a systematic overview - the SENATOR Project ONTOP Series.
AB  - BACKGROUND: Physical frailty (PF) and sarcopenia are predictors of negative
      health outcomes such as falls, disability, hospitalization, and death. Some
      systematic reviews (SRs) have been published on different nonpharmacological
      treatments of frailty and sarcopenia using heterogeneous definitions of them.
      OBJECTIVE: To critically appraise the evidence from SRs of the primary studies on
      nonpharmacological interventions to treat PF (defined by Fried's frailty
      phenotype) and sarcopenia (defined by the EWGSOP) in older patients. DESIGN:
      Overview of SRs and meta-analysis of comparative studies. DATA SOURCES: PubMed,
      Cochrane Database of Systematic Reviews, EMBASE, and CINAHL were searched in
      October 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: SRs that included at
      least one comparative study evaluating any nonpharmacological intervention to
      treat PF or sarcopenia in older patients in any health care setting. Any primary
      study described in these SRs with experimental design was included. DATA
      EXTRACTION AND MANAGEMENT: Two reviewers independently screened titles,
      abstracts, and full-texts of articles. Quality assessment was carried out by
      using criteria from the Cochrane Collaboration and the GRADE working group.
      RESULTS: Ten SRs with 5 primary studies satisfied the inclusion criteria. The
      most frequent interventions in the included studies were physical exercise (4)
      and nutritional supplementation (2). Muscle strength (MS; except for one study in
      a frail population) and physical performance (PP; except for another study in a
      frail population) improved with exercise and amino acid supplementation in frail
      and sarcopenic old adults. Falls and activities of daily living were assessed in
      two studies with opposite results. The overall quality of the evidence was low.
      CONCLUSION: This overview of SRs highlights the importance of exercise
      interventions with or without nutritional supplementation to improve the PP in
      community-dwelling patients aged >65 years with PF and sarcopenia. MS improved
      with multidisciplinary treatment and exercise interventions in this population.

PMID- 28490867
TI  - Promoting the inclusion of vital-capacity data in the bronchodilator response.

PMID- 28490868
TI  - Serum IL-1beta and IL-17 levels in patients with COPD: associations with clinical
      parameters.
AB  - COPD is a chronic airway inflammatory disease characterized mainly by neutrophil
      airway infiltrations. Interleukin (IL)-1beta and IL-17 are the key mediators of
      neutrophilic airway inflammation in COPD. This study was undertaken to evaluate
      the serum IL-1beta and IL-17 levels and associations between these two key
      mediators with clinical parameters in COPD patients. Serum samples were collected
      from 60 COPD subjects during the acute exacerbation of COPD, 60 subjects with
      stable COPD and 40 healthy control subjects. Commercial enzyme-linked
      immunosorbent assay kits were used to measure the serum IL-1beta and IL-17
      concentrations. The association between serum IL-1beta and IL-17 with FEV1%
      predicted, C-reactive protein, neutrophil percentage and smoking status (pack
      years) was assessed in the COPD patients. We found that serum IL-1beta and IL-17
      levels in acute exacerbation of COPD subjects were significantly higher than that
      in stable COPD or control subjects and were positively correlated to serum C
      reactive protein levels, neutrophil % and smoking status (pack-years) but
      negatively correlated with FEV1% predicted in COPD patients. More importantly,
      serum IL-1beta levels were markedly positively associated with serum IL-17 levels
      in patients with COPD (P=0.741, P<0.001). In conclusion, elevated serum IL-1beta
      and IL-17 levels may be used as a biomarker for indicating persistent
      neutrophilic airway inflammation and potential ongoing exacerbation of COPD.

PMID- 28490869
TI  - Pulmonary infection control window as a switching point for sequential
      ventilation in the treatment of COPD patients: a meta-analysis.
AB  - PURPOSE: Choosing the appropriate time to switch to noninvasive positive-pressure
      ventilation (NPPV) plays a crucial role in promoting successful weaning. However,
      optimal timing for transitioning and weaning patients from mechanical ventilation
      (MV) to NPPV has not been clearly established. In China, the pulmonary infection
      control (PIC) window as a switching point for weaning from MV has been performed
      for many years, without definitive evidence of clinical benefit. This study aimed
      to summarize the evidence for NPPV at the PIC window for patients with
      respiratory failure from COPD. METHODS: A comprehensive search for randomized
      controlled trials (RCTs) was performed. The trials were all parallel studies
      comparing the PIC window weaning strategy versus conventional weaning strategy in
      treatment of patients with respiratory failure due to COPD. RESULTS: Sixteen
      studies of 647 participants were eligible. When compared with conventional
      weaning strategy, early extubation followed by NPPV at the point of PIC window
      significantly reduced the mortality rate (risk ratios [RRs] 0.36, 95% confidence
      interval [CI] 0.23 to 0.57) and ventilator-associated pneumonia (VAP) (RR 0.28,
      95% CI 0.19 to 0.41); it also decreased the duration of invasive ventilation
      (weighted mean difference [WMD] -7.68 days, 95% CI -9.43 to -5.93) and total
      duration of ventilation (WMD -5.93 days, 95% CI -7.29 to -4.58), which also
      shortened the lengths of stay in an intensive care unit (WMD -8.51 days, 95% CI 
      10.23 to -6.79), as well as length of stay in hospital (WMD -8.47 days, 95% CI 
      8.61 to -7.33). CONCLUSION: The results showed that the PIC window as a switching
      point for sequential ventilation in treatment of respiratory failure in COPD
      patients may be beneficial. It might yield not only relevant information for
      caregivers in China but also new insights for considering the PIC window by
      physicians in other countries.

PMID- 28490870
TI  - Pre- and post-bronchodilator airway obstruction are associated with similar
      clinical characteristics but different prognosis - report from a population-based
      study.
AB  - INTRODUCTION: According to guidelines, the diagnosis of COPD should be confirmed
      by post-bronchodilator (post-BD) airway obstruction on spirometry; however, in
      clinical practice, this is not always performed. The aim of this population-based
      study was to compare clinical characteristics and prognosis, assessed as
      mortality, between subjects with airway obstruction divided into pre- but not
      post-BD obstruction, post-BD airway obstruction (COPD), and subjects without
      airway obstruction. MATERIALS AND METHODS: In 2002-2004, four adult population
      based cohorts were reexamined with spirometry and structured interview. Subjects
      with airway obstruction, with a ratio of forced expiratory volume in 1 s to
      (forced) vital capacity <0.70 (n=993), were identified together with sex- and age
      matched referents (n=993). These subjects were further divided into subjects with
      pre- but not post-BD airway obstruction (pre- not post-BD obstruction) and
      subjects with post-BD airway obstruction (COPD). Mortality data were collected
      until December 31, 2014. RESULTS: Out of 993 subjects with airway obstruction,
      736 (74%) had COPD and 257 (26%) pre- not post-BD obstruction. Any respiratory
      symptoms, allergic rhinitis, asthma, exacerbations, and comorbidities were
      equally common among subjects with COPD and pre- not post-BD obstruction, but
      less common among nonobstructive subjects. Mortality was highest among subjects
      with COPD and higher in men than in women. In both sexes, COPD, but not pre- not
      post-BD obstruction, was associated with an increased risk for death compared to
      those without airway obstruction. When COPD was divided into Global Initiative
      for Chronic Obstructive Lung Disease (GOLD) stages, GOLD 2 and 3-4 had an
      increased risk for death when compared to the nonobstructive group, also when
      adjusted for common confounders and comorbidities such as heart disease,
      diabetes, and anxiety/depression. CONCLUSION: Even though subjects with COPD and
      pre- not post-BD obstruction had fairly similar presentation of clinical
      characteristics, only those with COPD, specifically GOLD stage >=2, had increased
      risk for death when compared with nonobstructive subjects.

PMID- 28490871
TI  - Home noninvasive positive pressure ventilation with built-in software in stable
      hypercapnic COPD: a short-term prospective, multicenter, randomized, controlled
      trial.
AB  - BACKGROUND: The benefits of noninvasive positive pressure ventilation (NPPV) in
      patients with hypercapnic COPD are controversial. It is presumed that methodology
      and appropriate use of NIV ventilator might be crucial for the outcomes. With the
      new built-in software, the performance of NIV can be monitored at home, which can
      guarantee the compliance and appropriate use. This study investigated effects of
      home use of NIV in hypercapnia in COPD patients using the NIV ventilator with
      built-in software for monitoring. METHODS: The current multicenter prospective,
      randomized, controlled trial enrolled patients with stable GOLD stages III and IV
      hypercapnic COPD. Patients were randomly assigned via a computer-generated
      randomization sequence, with a block size of four patients, to continue optimized
      treatment (control group) or to receive additional NPPV (intervention group) for
      3 months. The primary outcome was arterial carbon dioxide pressure (PaCO2). Data
      were derived from built-in software and analyzed every 4 weeks. Analysis was
      carried out with the intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT02499718. RESULTS: Patients were recruited from 20
      respiratory units in China from October 1, 2015, and recruitment was terminated
      with a record of the vital statistics on May 31, 2016. A total of 115 patients
      were randomly assigned to the NPPV group (n=57) or the control group (n=58).
      Patients complied well with NPPV therapy (mean [+/- standard deviation] day use
      5.6+/-1.4 h). The mean estimation of leaks was 37.99+/-13.71 L/min. The changes
      in PaCO2 (-10.41+/-0.97 vs -4.32+/-0.68 mmHg, P=0.03) and 6-min walk distance
      (6MWD) (38.2% vs 18.2%, P=0.02) were statistically significant in the NPPV group
      versus the control group. COPD assessment test (CAT) showed a positive trend
      (P=0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not
      different between groups. CONCLUSION: Ventilators equipped with built-in software
      provided methodology for monitoring NIV use at home, which could facilitate the
      improvement of compliance and quality control of NIV use. It was shown that three
      months use of NIV at home could reduce the PaCO2 and improve exercise tolerance
      (6MWD) in chronic hypercapnic COPD patients.

PMID- 28490872
TI  - Correlation between fractional exhaled nitric oxide and sputum eosinophilia in
      exacerbations of COPD.
AB  - INTRODUCTION: Measurements of eosinophils in induced sputum and fractional
      exhaled nitric oxide (FeNO) are noninvasive biomarkers for assessing airway
      inflammation phenotypes in chronic obstructive pulmonary disease (COPD).
      Nevertheless, the clinical application of the correlation between FeNO levels and
      sputum eosinophilia is controversial. The study aimed to investigate the
      correlation and predictive relationship between FeNO levels and sputum
      eosinophils in patients with COPD exacerbation. It also examined the relationship
      between FeNO levels and blood eosinophil percentage. METHODS: A total of 163
      patients with COPD exacerbation were included in the cross-sectional study. All
      patients underwent the following on the same day: FeNO test, spirometry,
      bronchodilator reversibility test, induced sputum, and routine blood test. They
      were classified as eosinophilic group or noneosinophilic group based on sputum
      eosinophilic percentage (>=2.5%)/FeNO levels (>=32 parts per billion [ppb]).
      RESULTS: FeNO levels and blood eosinophilic percentage were higher in patients
      with sputum eosinophilia (n=62) compared to those without (31.35 ppb versus 21.43
      ppb, P=0.015; 2.71% versus 0.98%, P<0.0001, respectively). Sputum eosinophilic
      percentage was higher with raised FeNO (n=34) compared to those with FeNO <32 ppb
      (5.12% versus 3.12%, P=0.007). Eosinophils in induced sputum correlated with both
      FeNO levels (rho=0.221, P=0.005) and blood eosinophilic percentage (rho=0.399,
      P<0.001). There was no relationship between FeNO and blood eosinophilic
      percentage. Blood eosinophilic percentage was predictive of sputum eosinophilia
      (95% confidence interval [CI] =0.65-0.81, P<0.001) at a cutoff point of 0.65%
      (sensitivity =73%, specificity =61.3%). FeNO levels were predictive of sputum
      eosinophilia (95% CI =0.53-3,071, P=0.012) at a cutoff point of 17.5 ppb
      (sensitivity =65.1%, specificity =56.4%). CONCLUSION: The clinical relevance of
      this study provides evidence that inflammatory biomarkers, including sputum
      eosinophilic percentage, FeNO level, and blood eosinophilic percentage, can be
      used to positively diagnose eosinophilic COPD. The FeNO level and blood
      eosinophilic counts/percentage, which determine an optimal cutoff for sputum
      eosinophilia, need more studies.

PMID- 28490873
TI  - Tailoring stimuli-responsive delivery system driven by metal-ligand coordination
      bonding.
AB  - In this study, a novel coordination bonding system based on metal-tannic acid
      (TA) architecture on zein/carboxymethyl chitosan (CMCS) nanoparticles (NPs) was
      investigated for the pH-responsive drug delivery. CMCS has been reported to coat
      on zein NPs as delivery vehicles for drugs or nutrients in previous studies. The
      cleavage of either the "metal-TA" or "NH2-metal" coordination bonds resulted in
      significant release of guest molecules with high stimulus sensitivity, especially
      in mild acidic conditions. The prepared metal-TA-coated zein/CMCS NPs (zein/CMCS
      TA/metal NPs) could maintain particle size in cell culture medium at 37 degrees
      C, demonstrating good stability compared with zein/CMCS NPs. In vitro release
      behavior of doxorubicin hydrochloride (DOX)-loaded metal-TA film-coated zein/CMCS
      NPs (DOX-zein/CMCS-TA/metal NPs) showed fine pH responsiveness tailored by the
      ratio of zein to CMCS as well as the metal species and feeding concentrations.
      The blank zein/CMCS-TA/metal NPs (NPs-TA/metal) were of low cytotoxicity, while a
      high cytotoxic activity of DOX-zein/CMCS-TA/metal NPs (DOX-NPs-TA/metal) against
      HepG2 cells was demonstrated by in vitro cell assay. Confocal laser scanning
      microscopy (CLSM) and flow cytometry were combined to study the uptake efficiency
      of DOX-NPs or DOX-NPs-TA/metal. This system showed significant potential as a
      highly versatile and potent platform for drug delivery.

PMID- 28490874
TI  - Quantitative and multiplexed detection for blood typing based on quantum dot
      magnetic bead assay.
AB  - BACKGROUND: Accurate and reliable blood grouping is essential for safe blood
      transfusion. However, conventional methods are qualitative and use only single
      antigen detection. We overcame these limitations by developing a simple,
      quantitative, and multiplexed detection method for blood grouping using quantum
      dots (QDs) and magnetic beads. METHODS: In the QD fluorescence assay (QFA), blood
      group A and B antigens were quantified using QD labeling and magnetic beads, and
      the blood groups were identified according to the R value (the value was
      calculated with the fluorescence intensity from dual QD labeling) of A and B
      antigens. The optimized performance of QFA was established by blood typing 791
      clinical samples. RESULTS: Quantitative and multiplexed detection for blood group
      antigens can be completed within 35 min with more than 105 red blood cells. When
      conditions are optimized, the assay performance is satisfactory for weak samples.
      The coefficients of variation between and within days were less than 10% and the
      reproducibility was good. The ABO blood groups of 791 clinical samples were
      identified by QFA, and the accuracy obtained was 100% compared with the tube
      test. Receiver-operating characteristic curves revealed that the QFA has high
      sensitivity and specificity toward clinical samples, and the cutoff points of the
      R value of A and B antigens were 1.483 and 1.576, respectively. CONCLUSION: In
      this study, we reported a novel quantitative and multiplexed method for the
      identification of ABO blood groups and presented an effective alternative for
      quantitative blood typing. This method can be used as an effective tool to
      improve blood typing and further guarantee clinical transfusion safety.

PMID- 28490875
TI  - Mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes.
AB  - Ethosomes can promote the penetration of lipophilic drugs into the skin, but the
      underlying mechanism is still unknown. The purpose of this study was to
      investigate the mechanism of transdermal permeation promotion of lipophilic drugs
      by ethosomes. The formulation of ethosomes was optimized using the Box-Behnken
      experimental design, in which Rhodamine B and 1-palmitoyl-2-{12-[(7-nitro-2-1,3
      benzoxadiazol-4-yl)amino]dodecanoyl}-sn-glycero-3-phosphocholine were used to
      simulate a model lipophilic drug and act as a fluorescent tracer of ethosomal
      phospholipids, respectively. Liposomes with the same phospholipid concentration
      and a hydroethanolic solution with the same ethanol concentration were also
      prepared as controls. The percutaneous progression of the above fluorescent
      preparations was observed by confocal laser scanning microscopy, and the
      fluorescence intensity of the images was analyzed. The optimized ethosome
      formulation consisted of 2.45% yolk phospholipids, 30% ethanol, and 67.55%
      distilled water. The percutaneous permeation of Rhodamine B in the optimized
      ethosomes was superior to that in hydroethanolic solution (P<0.05) and liposomes
      (P<0.05). The ethosomes could penetrate the skin via the percutaneous pathway of
      the hair follicle and stratum corneum, while during the process of penetration,
      the vesicles were broken and the phospholipids were retained in the upper
      epidermis, with the test compounds penetrating gradually. The superior
      percutaneous penetration of ethosomes was linked to the synergistic effects of
      their ingredients. The percutaneous pathways of ethosomes included open hair
      follicles and stratum corneum pathways. In addition, the vesicles might break up
      during percutaneous penetration in the superficial layer of the skin, allowing
      the test compounds to keep permeating into the deeper layer alone, while the
      phospholipid was retained in the upper epidermis.

PMID- 28490876
TI  - One-pot synthesis of dextran-coated iron oxide nanoclusters for real-time
      regional lymph node mapping.
AB  - The intraoperative precision cleaning of lymph nodes (LNs) is an essential
      component of treating neoplastic disease. To develop efficient probes for the
      targeted detection of LNs that could act as carriers for the specific diagnosis
      and treatment of metastatic LNs in the future, dextran-coated iron oxide
      nanoclusters (DIONs) were synthesized using a one-pot coprecipitation procedure.
      These modified DIONs have good water dispersibility, cytocompatibility, an
      optimum size, and a stable, dark brown color for LN imaging. In this study,
      cytotoxicity was evaluated using lymphatic endothelial cells (LECs) to predict
      biosafety and biocompatibility. Most importantly, the effectiveness of DIONs in
      mapping perigastric LNs in Sprague Dawley rats following injection into the
      gastric submucosal layer was demonstrated. In addition, a long-term tracing in
      vivo (from 4 days to 3 months) indicated that the DIONs had good biosafety and
      biocompatibility according to an evaluation of the behavior and blood
      biochemistry of the rat and a histopathological examination of the important
      organs.

PMID- 28490877
TI  - Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity
      for intelligent co-delivery of paclitaxel and siRNA to breast tumor.
AB  - Multidrug resistance (MDR) is a major obstacle for the clinical therapy of
      malignant human cancers. The discovery of RNA interference provides efficient
      gene silencing within tumor cells for reversing MDR. In this study, a new "binary
      polymer" low-density lipoprotein-N-succinyl chitosan-cystamine-urocanic acid (LDL
      NSC-SS-UA) with dual pH/redox sensitivity and targeting effect was synthesized
      for the co-delivery of breast cancer resistance protein small interfering RNA
      (siRNA) and paclitaxel (PTX). In vivo, the co-delivering micelles can accumulate
      in tumor tissue via the enhanced permeability and retention effect and the
      specific recognition and combination of LDL and LDL receptor, which is
      overexpressed on the surface of tumor cell membranes. The siRNA-PTX-loaded
      micelles inhibited gene and drug release under physiological conditions while
      promoting fast release in an acid microenvironment or in the presence of
      glutathione. The micelles escaped from the lysosome through the proton sponge
      effect. Additionally, the micelles exhibited superior antitumor activity and
      downregulated the protein and mRNA expression levels of breast cancer resistance
      protein in MCF-7/Taxol cells. The biodistribution and antitumor studies proved
      that the siRNA-PTX-loaded micelles possessed prolonged circulation time with a
      remarkable tumor-targeting effect and effectively inhibited tumor growth.
      Therefore, the novel dual pH/redox-sensitive polymers co-delivering siRNA and PTX
      with excellent biocompatibility and effective reversal of MDR demonstrate a
      considerable potential in cancer therapy.

PMID- 28490879
TI  - Methodological assessment of the reduction of the content of impurities in
      nimodipine emulsion via the use of 21 amino acid protection.
AB  - PURPOSE: The present study examined the factors affecting the content of
      impurities of nimodipine (NMP) emulsion and the associated methods of compound
      protection. METHODS: Destructive testing of NMP emulsion and its active
      pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used
      to study the content of impurities in two phases. The impurity of NMP was
      measured under different potential of hydrogen (pH) conditions, antioxidants and
      pH-adjusting agents. RESULTS: Following destruction, the degradation of NMP
      notably occurred in the basic environment. The consumption of the pH-adjusting
      agent NaOH was proportional to the production of impurities since the inorganic
      base and/or acid promoted the degradation of NMP. The organic antioxidants,
      notably amino acids with an appropriate length of intermediate chain and electron
      donating side group, exhibited improved antioxidant effects compared with
      inorganic antioxidants. The minimal amount of impurities was produced following
      addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of
      the pH to a range of 7.5-8.0 in the presence of acetic acid solution. CONCLUSION:
      NMP was more prone to degradation in an oxidative environment, in an aqueous
      phase and/or in the presence of inorganic pH-adjusting agents and antioxidants.
      The appropriate antioxidant and pH-adjusting agent should be selected according
      to the chemical structure, while destructive testing of the drug is considered to
      play the optimal protective effect.

PMID- 28490878
TI  - A novel injectable calcium phosphate-based nanocomposite for the augmentation of
      cannulated pedicle-screw fixation.
AB  - Polymethyl methacrylate (PMMA)-augmented cannulated pedicle-screw fixation has
      been routinely performed for the surgical treatment of lumbar degenerative
      diseases. Despite its satisfactory clinical outcomes and prevalence, problems and
      complications associated with high-strength, stiff, and nondegradable PMMA have
      largely hindered the long-term efficacy and safety of pedicle-screw fixation in
      osteoporotic patients. To meet the unmet need for better bone cement for
      cannulated pedicle-screw fixation, a new injectable and biodegradable
      nanocomposite that was the first of its kind was designed and developed in the
      present study. The calcium phosphate-based nanocomposite (CPN) exhibited better
      anti-pullout ability and similar fluidity and dispersing ability compared to
      clinically used PMMA, and outperformed conventional calcium phosphate cement
      (CPC) in all types of mechanical properties, injectability, and biodegradability.
      In term of axial pullout strength, the CPN-augmented cannulated screw reached the
      highest force of ~120 N, which was higher than that of PMMA (~100 N) and CPC (~95
      N). The compressive strength of the CPN (50 MPa) was three times that of CPC, and
      the injectability of the CPN reached 95%. In vivo tests on rat femur revealed
      explicit biodegradation of the CPN and subsequent bone ingrowth after 8 weeks.
      The promising results for the CPN clearly suggest its potential for replacing
      PMMA in the application of cannulated pedicle-screw fixation and its worth of
      further study and development for clinical uses.

PMID- 28490880
TI  - Protective efficacy of a single salvianolic acid A treatment on photothrombosis
      induced sustained spatial memory impairments.
AB  - With respect to the high burden of ischemic stroke and the absence of
      pharmacological treatment for promoting rehabilitation, promising candidates with
      specific effects on long-term functional recovery are highly desired. Candidates
      need reasonable experimental paradigms to evaluate the long-term functional
      outcome focused on ischemia-induced sensorimotor and memory deficits. "Danshen",
      a traditional Chinese herb, has long been used to treat coronary and cerebral
      vascular diseases as well as dementia. Salvianolic acid A (SAA), one of the major
      active ingredients of Danshen, was demonstrated to be effective in protecting
      against cerebral ischemic injury. Here, employing an experimental stroke model
      induced by photothrombosis in the unilateral frontal cortex of rats, we
      investigated whether SAA has long-term protective effects on ischemia-induced
      sensorimotor and memory deficits in our behavioral tests. The results indicated
      that a single SAA treatment improved the cortical ischemia-induced sensorimotor
      deficits during 15 days' cylinder test period, and alleviated ischemia-induced
      sustained spatial memory impairments during the 2 months' dependent Morris Water
      Maze (MWM) tests. In addition, either ischemic injury or SAA treatment did not
      show any changes compared with sham group in other behavioral tests including
      rotarod tests, swimming speed in MWM tests, open field tests, elevated plus maze
      tests, treadmill tests and forced swimming tests. The results reveal that the
      cognitive deficits are not the results of animal's anxiety or confounding motor
      impairments. Overall, the present paradigm appears suitable for the preclinical
      evaluation of the long-term effects of pharmacological treatments on ischemic
      stroke. Meanwhile, SAA might have therapeutic potential for the treatment of
      memory deficits associated with ischemic stroke.

PMID- 28490881
TI  - Risk of obstructive sleep apnea and excessive daytime sleepiness in hospitalized
      psychiatric patients.
AB  - OBJECTIVES: This study evaluated the risk of developing obstructive sleep apnea
      (OSA) and excessive daytime sleepiness (EDS) in hospitalized psychiatric patients
      at the American University of Beirut Medical Center (AUB-MC). Factors associated
      with OSA and EDS occurrence in this sample were also examined. METHODS: The
      Berlin questionnaire and the Epworth sleepiness scale; which respectively
      evaluate OSA and EDS symptoms, were administered to individuals hospitalized at
      an acute psychiatric treatment unit at the AUB-MC between the dates of January
      2014 and October 2016. Additional data collected included general demographics,
      psychiatric diagnoses, and questionnaires evaluating depression and anxiety
      symptoms. Statistical analyses utilizing SPSS were performed to determine the
      prevalence of OSA and EDS, as well as their respective associations with patient
      profiles. RESULTS: Our results showed that 39.5% of participants were found to
      have a high risk of sleep apnea and 9.9% of the participants were found to have
      abnormal daytime sleepiness. The risk of developing OSA was associated with a
      higher body mass index (BMI) (P=0.02), and depression severity (patient health
      questionnaire 9 score) (P=0.01). Increasing severity of depressive symptoms was
      associated with a higher risk of sleep apnea (P=0.01). BMI (odds ratio [OR]
      =5.97, 95% confidence interval [CI] 1.89-18.82) and depression severity (OR
      =4.04, 95% CI 1.80-9.07) were also found to be predictors of OSA. The psychiatric
      diagnoses of the participants were not found to have a significant association
      with the risk of sleep apnea. CONCLUSION: The risk of OSA is increased among
      hospitalized psychiatric patients, and this condition can have detrimental
      effects on psychiatric patients. OSA appears to be under-recognized in this
      population, psychiatrists should screen for OSA in hospitalized psychiatric
      patients and refer them for diagnostic testing or treatment when indicated.

PMID- 28490882
TI  - Connectivity to computers and the Internet among patients with schizophrenia
      spectrum disorders: a cross-sectional study.
AB  - PURPOSE: Information and communication technologies have been developed for a
      variety of health care applications and user groups in the field of health care.
      This study examined the connectivity to computers and the Internet among patients
      with schizophrenia spectrum disorders (SSDs). PATIENTS AND METHODS: A cross
      sectional survey design was used to study 311 adults with SSDs from the inpatient
      units of two psychiatric hospitals in Finland. The data collection lasted for 20
      months and was done through patients' medical records and a self-reported,
      structured questionnaire. Data analysis included descriptive statistics. RESULTS:
      In total, 297 patients were included in this study (response rate =96%). More
      than half of them (n=156; 55%) had a computer and less than half of them (n=127;
      44%) had the Internet at home. Of those who generally had access to computers and
      the Internet, more than one-fourth (n=85; 29%) used computers daily, and >30%
      (n=96; 33%) never accessed the Internet. In total, approximately one-fourth of
      them (n=134; 25%) learned to use computers, and less than one-third of them
      (n=143; 31%) were known to use the Internet by themselves. Older people (aged 45
      65 years) and those with less years of education (primary school) tended not to
      use the computers and the Internet at all (P<0.001), and younger people and those
      with higher education were associated with more active use. CONCLUSION: Patients
      had quite good access to use computers and the Internet, and they mainly used the
      Internet to seek information. Social, occupational, and psychological functioning
      (which were evaluated with Global Assessment of Functioning) were not associated
      with access to and frequency of computer and the Internet use. The results
      support the use of computers and the Internet as part of clinical work in mental
      health care.

PMID- 28490883
TI  - Retrospective analysis of non-laboratory-based adverse drug reactions induced by
      intravenous radiocontrast agents in a Joint Commission International-accredited
      academic medical center hospital in China.
AB  - The authors retrospectively analyzed the pattern and characteristics of non
      laboratory-based adverse drug reactions (ADRs) induced by intravenous
      radiocontrast agents in a large-scale hospital in China during 2014-2015. There
      were 314 ADR cases among 118,208 patients receiving enhanced CT or MRI
      examinations. The frequency of moderate/severe ADRs defined by Chinese Society of
      Radiology (ie, severe vomiting, systematic urticaria, facial swelling, dyspnea,
      vasovagal reaction, laryngeal edema, seizure, trembling, convulsions,
      unconsciousness, shock, death, and other unexpected adverse reactions) was rare
      (0.0431%), whereas the mild ADRs were uncommon (0.2225%) and accounted for 83.76%
      of ADRs. Frequency of ADRs induced by iodinated contrast agents was related with
      examination site, sex, and type of patient settings (P<0.01) and was higher
      compared with gadolinium contrast agents (0.3676% vs 0.0504%, P<0.01). From 2014
      to 2015, frequencies of total and moderate/severe ADRs induced by iodinated
      contrast agents decreased significantly (0.4410% vs 0.2947%, P<0.01; 0.0960% vs
      0.0282%, P<0.01, respectively). Frequency of ADRs differed among different
      iodinated contrast and gadolinium contrast (P<0.05) agents. Iopromide's ADR
      frequency in 2014 was significantly higher compared with iopamidol, ioversol, or
      iohexol (P<0.01). Frequency of moderate/severe ADRs induced by iodixanol was 4.1
      5.4 times that of iohexol, iopromide, or iopamidol. Rash was the predominant ADR
      subtype (84.39%) and occurred more frequently with iodixanol compared with
      iohexol, iopamidol, or ioversol (P<0.01). Overall, 21.97% of ADR cases had
      allergy history or atopy traits, and these cases experienced ADRs earlier than
      the negative ones (17.19 min vs 85.34 min, P<0.01). The mean time to onset of
      ADRs was increased in patients receiving iodixanol compared with other iodinated
      contrast agents (323.77 min vs 42.36 min, P<0.01). Overall, 37.26% of ADRs
      occurred within 5 min and 84.08% of ADRs occurred within 30 min. Efficient
      quality improvement in decreasing ADRs induced by radiocontrast agents has been
      achieved by multidisciplinary collaboration.

PMID- 28490884
TI  - Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3,
      MMP-9 and TIMP-3 in psoriatic patients.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)
      are thought to be associated with the pathogenesis and spread of psoriatic
      disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9
      and TIMP-3 in plaque psoriasis patients prior to and following a course of
      ultraviolet B narrowband treatment with respect to disease advancement. METHODS:
      Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy
      volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were
      determined using enzyme-linked immunosorbent assay, while Psoriasis Area and
      Severity Index was used to define disease advancement. RESULTS: Plasma levels of
      MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients
      compared to healthy individuals. A course of ultraviolet B narrowband treatment
      resulted in a significant decline in the studied metalloproteinases. Furthermore,
      the concentration of selected tissue inhibitors was negatively correlated with
      baseline Psoriasis Area and Severity Index score. CONCLUSION: Our research
      highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis
      pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the
      analyzed metalloproteinases seem to be a valuable psoriasis biomarker.

PMID- 28490885
TI  - Treatment-related severe and fatal adverse events with molecular targeted agents
      in the treatment of advanced gastric cancer: a meta-analysis.
AB  - AIM: To perform a systematic review and meta-analysis of Phase III randomized
      controlled trials (RCTs) to determine the incidence and risk of severe adverse
      events (AEs) with molecular targeted agents (MTAs) in advanced/metastatic gastric
      cancer (GC) patients. METHODS: A comprehensive literature search for related
      trials published up to December 2015 was performed. Eligible studies were Phase
      III RCTs of advanced/metastatic GC patients assigned to MTAs or control group.
      Data were extracted by two authors for severe and fatal AEs (FAEs). RESULTS: A
      total of nine Phase III RCTs involved 4,934 GC patients were ultimately
      identified. The pooled results demonstrated that the addition of TAs to therapies
      in advanced GC significantly increased the risk of developing severe AEs
      (relative risk: 1.12, 95% confidence interval: 1.02-1.24, P=0.02), but not for
      FAEs (relative risk: 0.97, 95% confidence interval: 0.65-1.45, P=0.88).
      Additionally, the most common causes of FAEs with MTAs were infections (16.3%),
      gastrointestinal hemorrhage (8.2%), and arterial thromboembolic events (8.2%),
      respectively. CONCLUSION: With available evidence, the use of TAs in GC patients
      was associated with an increased risk of severe AEs, but not for FAE. Clinicians
      should be aware of the risk of severe AEs with the administration of these drugs
      in these patients.

PMID- 28490886
TI  - Apatinib to combat EGFR-TKI resistance in an advanced non-small cell lung cancer
      patient with unknown EGFR status: a case report.
AB  - Lung adenocarcinoma is the most common pathological pattern of lung cancer.
      During the past decades, a number of targeted agents have been explored to treat
      advanced lung adenocarcinoma. In the present clinical practice, antagonists of
      the epidermal growth factor receptor (EGFR) and vascular endothelial growth
      factor (VEGF)-directed therapies are widely used. In the former category, the
      agent erlotinib (tyrosine kinase inhibitor) has shown obvious advantages over
      cytotoxic therapy. Anti-VEGF therapy bevacizumab used for lung adenocarcinoma was
      recommended in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as
      first-line therapy. Similarly, apatinib is speculated to response by selectively
      inhibiting the vascular endothelial growth factor receptor-2. The patient with
      unknown EGFR status benefited 5-month progressive free survival (PFS) from
      erlotinib, and then another 5.1-month PFS with combined treatment of apatinib,
      which suggested a new option for lung adenocarcinoma. However, when dabigatran
      was used to cancer-related venous thromboembolism during apatinib therapy,
      extensive subcutaneous bleeding occurred, warning us against the risks of
      bleeding. Besides, hypertension and anorexia were observed, causing dosage
      adjustment.

PMID- 28490887
TI  - Role of CT scan in differentiating the type of colorectal cancer.
AB  - OBJECTIVES: Most colorectal cancers are classical adenocarcinomas (AC), and less
      frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell
      carcinomas (SC). The purpose of this study was to evaluate the computed
      tomography (CT) findings that can help to differentiate MAC and SC from AC.
      METHODS: CT scans of 168 patients with pathologically proven MAC and 67 patients
      with pathologically proven SC were analyzed, and 220 patients with classical AC
      were also included as a control group. CT findings of the three groups were
      compared and contrasted in terms of the bowel involvement patterns, contrast
      enhancement patterns, and presence or absence of bowel obstruction, intratumoral
      calcification, pericolic fat infiltration, and local tumor extension to adjacent
      organs. Statistical analyses were made by using the one-way analysis of variance,
      least significant difference test, and Pearson's chi-square test. RESULTS:
      Compared with classical AC, the MAC showed more severe (6.29+/-2.69 cm vs 4.57+/
      1.74 cm, P<0.001) and higher percentage of occurrence of eccentric bowel-wall
      thickening (37.2% vs 11.5%, P<0.001). Heterogeneous contrast enhancement was most
      common in MAC (P<0.01), and MAC showed more areas with hypoattenuation (P<0.001).
      The presence of intratumoral calcification was most frequent in MAC (17.9% vs 2%
      vs 6.8%) (P<0.001); the SC also were more severe (5.75+/-2.28 cm vs 4.57+/-1.74
      cm. P=0.001) than AC, but SC tend to show more cases of concentric even bowel
      wall thickening (67.2%); homogeneous contrast enhancement was most common in SC
      (P<0.01), and it showed a target appearance. The presence of peritoneal seeding
      was most frequent in SC (35.8% vs 8% vs 2.7%, P<0.001), while the presence of
      regional lymph node metastasis (P=0.190) and direct invasion of adjacent organs
      or metastasis (P=0.323) were not significantly different among them. CONCLUSION:
      Some radiological features by CT can be used to classify different colon tumor
      types.

PMID- 28490888
TI  - Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves
      relapse-free survival in adults with low- to intermediate-risk acute
      promyelocytic leukemia who have achieved complete remission after consolidation
      therapy.
AB  - BACKGROUND: Currently, the optimal maintenance therapy for patients with acute
      promyelocytic leukemia (APL) who have achieved complete remission (CR) after
      completing consolidation chemotherapy remains controversial. The comparative
      effectiveness of the all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3)
      maintenance strategy with classic ATRA plus chemotherapy has not been evaluated.
      In this study, we compared the efficacy and toxicity of maintenance therapy with
      ATRA plus As2O3 and classic ATRA plus chemotherapy in low- to intermediate-risk
      APL patients reaching the first CR after induction and consolidation therapy.
      METHODS: A retrospective review of 58 adult patients diagnosed with APL was
      conducted. After receiving consolidation therapy and achieving CR, 30 patients
      were administered maintenance therapy with an ATRA plus As2O3 regimen (ATRA+As2O3
      group), whereas 28 patients were administered 3-monthly cycles of an ATRA plus
      chemotherapy regimen (ATRA+chemotherapy group). RESULTS: Grade 3-4 neutropenia
      was significantly more frequent in the ATRA+chemotherapy group (N=9, 32.1%) than
      in the ATRA+As2O3 group (N=0) (P=0.001). At a median follow-up of 49.1 months
      (range: 9.7-97.4 months) from the completion of consolidation, no relapses were
      observed in the ATRA+As2O3 group, whereas seven relapses occurred in the
      ATRA+chemotherapy group. The risk of relapse in the patients administered
      ATRA+As2O3 maintenance was significantly lower than that in those administered
      ATRA+chemotherapy maintenance (P=0.004). Based on log-rank analysis, only
      maintenance therapy with ATRA and As2O3 was associated with a significantly
      higher relapse-free survival (P=0.0159). CONCLUSION: Maintenance therapy with
      ATRA and As2O3 was beneficial in low- to intermediate-risk APL patients who were
      effectively treated to achieve CR. Further clinical trials with reliable designs
      are needed to confirm these observations.

PMID- 28490890
TI  - Erratum: B-cell-specific Moloney murine leukemia virus integration site 1:
      potential stratification factor and therapeutic target for epithelial ovarian
      cancer [Corrigendum].
AB  - [This corrects the article on p. 5203 in vol. 9, PMID: 27578986.].

PMID- 28490889
TI  - Identification of potential biomarkers and analysis of prognostic values in head
      and neck squamous cell carcinoma by bioinformatics analysis.
AB  - The purpose of this study was to find disease-associated genes and potential
      mechanisms in head and neck squamous cell carcinoma (HNSCC) with deoxyribonucleic
      acid microarrays. The gene expression profiles of GSE6791 were downloaded from
      the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were
      obtained with packages in R language and STRING constructed protein-protein
      interaction (PPI) network of the DEGs with combined score >0.8. Subsequently,
      module analysis of the PPI network was performed by Molecular Complex Detection
      plugin and functions and pathways of the hub gene in subnetwork were studied.
      Finally, overall survival analysis of hub genes was verified in TCGA HNSCC
      cohort. A total of 811 DEGs were obtained, which were mainly enriched in the
      terms related to extracellular matrix (ECM)-receptor interaction, ECM structural
      constituent, and ECM organization. A PPI network was constructed, consisting of
      401 nodes and 1,254 edges and 15 hub genes with high degrees in the network. High
      expression of 4 genes of the 15 genes was associated with poor OS of patients in
      HNSCC, including PSMA7, ITGA6, ITGB4, and APP. Two significant modules were
      detected from the PPI network, and the enriched functions and pathways included
      proteasome, ECM organization, and ECM-receptor interaction. In conclusion, we
      propose that PSMA7, ITGA6, ITGB4, and APP may be further explored as potential
      biomarkers to aid HNSCC diagnosis and treatment.

PMID- 28490891
TI  - No genetic relationship between TLR2 rs4696480, rs3804100, and rs3804099 gene
      polymorphisms and female breast cancer in Saudi populations.
AB  - Breast cancer (BC) is the most common cause of cancer-related deaths among women
      in the Kingdom of Saudi Arabia. An association between the dysregulation of
      innate immunity, primarily the deregulation of Toll-like receptors (TLRs), and BC
      development was described a long time ago. Several studies have reported that BC
      risk factors appear to be related to the interaction between certain genes and
      exposure to various environmental factors. Here, we investigated the potential
      correlation of three TLR2 single-nucleotide polymorphisms (SNPs; rs3804100,
      rs4696480, and rs3804099) with the development of BC in female patients from
      Saudi Arabia. We collected 126 blood samples from women with BC and 146 blood
      samples from healthy women without any clinical signs of BC. The genotypic
      frequencies of TLR2 polymorphisms were assayed. Our results showed that the
      genotypic and allelic frequencies of TLR2 did not differ significantly between BC
      patients and healthy controls. However, the distributions of rs3804100 (1350 T/C)
      genotypes in BC groups were 1%, 19%, and 80% for CC, CT, and TT, respectively. In
      the control group, the rs3804100 (1350 T/C) genotype distributions were 3%, 18%,
      and 79% for CC, CT, and TT, respectively. The SNP rs3804100 homozygous "TT"
      genotype was not associated with the risk of developing BC in the BC patients
      compared with controls (odds ratio [OR], 4.5; confidence interval [CI], 0.49
      41.02; P=0.145). The TLR2 rs4696480 AA genotype was observed in 23% of BC
      patients compared to 18% of control individuals, the AT genotype was seen in 40%
      of BC patients and 46% of control individuals, and the TT genotype was observed
      in 37% of BC patients and 36% of normal controls. Our results did not show any
      difference in genotypic frequency between BC patients and normal controls for the
      TLR2 rs3804099 SNP; however, the (C) phenotypic frequency was 49% in BC patients
      and 53% in controls. The (T) phenotypic frequency was 51% and 47% in BC patients
      and normal patients, respectively. These findings indicate that there is no
      association between the TLR2 polymorphisms tested and BC susceptibility in the
      female population from the Kingdom of Saudi Arabia. We suggest using other TLR2
      SNPs to investigate the possible relationship between innate immunity
      deregulation by disruption of TLR2 and potential BC development.

PMID- 28490892
TI  - The effectiveness of EGFR-TKIs against brain metastases in EGFR mutation-positive
      non-small-cell lung cancer.
AB  - Brain metastases are usual in non-small-cell lung cancer (NSCLC) with poor
      prognosis and few available therapeutic options. This retrospective study aims to
      evaluate the efficacy of epidermal growth factor receptor-tyrosine kinase
      inhibitors (EGFR-TKIs) against brain metastases from NSCLC harboring activating
      EGFR mutation. A total of 148 patients with brain metastases from EGFR mutation
      positive NSCLC were analyzed retrospectively. The patients were orally given
      gefitinib (250 mg) or erlotinib (150 mg) once a day until intracranial disease
      progression, death, or intolerable side effects. A survival analysis was done
      using the Kaplan-Meier analysis and log-rank test. Objective response rate and
      disease control rate within brain lesions were 36.5% and 87.2%, respectively,
      with a median progression-free survival (PFS) and overall survival (OS) of 11.2
      months (95% confidence interval [CI], 10.1-12.3) and 13.6 months (95% CI, 12.3
      14.9), respectively. The patients' characteristics were not statistically
      associated with PFS and OS. EGFR-TKIs showed promising antitumor activity against
      brain metastases in NSCLC patients with activating EGFR mutation and might be the
      treatment choice in this clinical setting.

PMID- 28490894
TI  - Uniform-related infection control practices of dental students.
AB  - BACKGROUND: Uniform-related infection control practices are sometimes overlooked
      and underemphasized. In Saudi Arabia, personal protective equipment must meet
      global standards for infection control, but the country's Islamic legislature
      also needs to be taken into account. AIM: To assess uniform-related infection
      control practices of a group of dental students in a dental school in Saudi
      Arabia and compare the results with existing literature related to cross
      contamination through uniforms in the dental field. METHOD: A questionnaire was
      formulated and distributed to dental students at King Abdulaziz University
      Faculty of Dentistry in Jeddah, Saudi Arabia, which queried the students about
      their uniform-related infection control practices and their methods and frequency
      of laundering and sanitizing their uniforms, footwear, and name tags. RESULTS:
      There is a significant difference between genders with regard to daily uniform
      habits. The frequency of uniform washing was below the standard and almost 30% of
      students were not aware of how their uniforms are washed. Added to this, there is
      no consensus on a unified uniform for male and female students. CONCLUSION:
      Information on preventing cross-contamination through wearing uniforms must be
      supplied, reinforced, and emphasized while taking into consideration the cultural
      needs of the Saudi society.

PMID- 28490893
TI  - Sesame allergy: current perspectives.
AB  - Sesame is an important global allergen affecting ~0.1% of the North American
      population. It is a major cause of anaphylaxis in the Middle East and is the
      third most common food allergen in Israel. We conducted a systematic review of
      original articles published in the last 10 years regarding the diagnosis and
      management of sesame allergy. Skin prick testing appears to be a useful predictor
      of sesame allergy in infants, although data are less consistent in older children
      and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor,
      especially in studies that used oral food challenges to confirm the diagnosis.
      Double-blind, placebo-controlled food challenge thus remains the diagnostic gold
      standard for sesame allergy. The cornerstone of sesame allergy management is
      allergen avoidance, though accidental exposures are common and patients must be
      prepared to treat the consequent reactions with epinephrine. Novel diagnostic and
      treatment options such as component-resolved diagnostics, basophil activation
      testing, and oral immunotherapy are under development but are not ready for
      mainstream clinical application.

PMID- 28490895
TI  - Healthcare resource consumption and cost of care among patients with polycystic
      kidney disease in Italy.
AB  - OBJECTIVE: The aim of this study was to assess healthcare resource consumption
      and its associated costs among patients with polycystic kidney disease (PKD) in a
      real-world setting. METHODS: An observational retrospective cohort analysis was
      conducted using data from the administrative databases of four Italian local
      health units. Data for patients who were diagnosed with PKD during the inclusion
      period (January 1, 2010 to December 31, 2012) were extracted. The date on which a
      patient's first PKD hospitalization occurred during the inclusion period was
      defined as the index date (ID), and the ID was defined as the date of the first
      dialysis treatment recorded during the inclusion period for patients undergoing
      dialysis. Data regarding the clinical characteristics of patients included in the
      study during the 12 months prior to the ID (pre-ID; characterization period) were
      collected. All patients were then followed up for the 12 months following the ID
      (post-ID; follow-up period). Healthcare consumption and its associated costs were
      analyzed during the follow-up period. All costs are reported in euros (?).
      RESULTS: A total of 1,123 patients with PKD were included in this study, 61.9% of
      whom were male; the mean age of the patients was 57.7+/-24.5 years. At diagnosis,
      11.2% and 1.1% of patients were affected by the dominant and recessive forms of
      PKD, respectively. Approximately 8% of the included patients were undergoing
      dialysis at ID (baseline). The incidence of dialysis was fourfold greater among
      patients with autosomal-dominant PKD (ADPKD) than among the total cohort (33.3%
      compared with an overall 8.3%). During the follow-up period, the average annual
      rates of healthcare resource consumption were greater among dialyzed than non
      dialyzed patients. The average healthcare expenditures were ?45,059.62 and
      ?3,913.89 (p<0.001) per year for dialyzed and non-dialyzed PDK patients,
      respectively. Our findings suggest that in the real-world Italian context,
      consumption of healthcare among patients with PKD has increased at dialysis
      initiation due to the cost of outpatient specialist healthcare services as well
      as other costs. Research on the prevention of PKD-related complications and
      disease progression may help to facilitate a decrease in the costs associated
      with this condition.

PMID- 28490896
TI  - Granuloma annulare: relationship to diabetes mellitus, thyroid disorders and
      tuberculin skin test.
AB  - BACKGROUND: Granuloma annulare is a benign inflammatory disease of the skin. The
      etiology and pathogenesis of the disease are not yet determined, but some authors
      have proposed that it might be associated with a variety of underlying conditions
      such as thyroid disorders, diabetes mellitus and positive tuberculin skin test.
      OBJECTIVE: This study was conducted to find the probable relationship between
      granuloma annulare and diabetes mellitus, thyroid disorders and positive
      tuberculin skin test. PATIENTS AND METHODS: A total of 28 patients with granuloma
      annulare were recruited from our dermatology outpatient clinic, and data on sex,
      age and distribution of granuloma annulare lesions were collected. Forty-one age-
      and sex-matched apparently healthy volunteers serving as controls were also
      included. Thyroid stimulating hormone (TSH), fasting blood sugar (FBS) and
      tuberculin skin tests were performed for both groups. RESULTS: Mean serum level
      of FBS in the patient group was significantly higher than the mean serum level of
      FBS in the control group (110.60+/-46.31 mg/dL versus 88.39+/-10.58 mg/dL,
      respectively, p=0.004). Mean serum level of TSH in the patient group was 3.43+/
      2.73 mIU/L, which was not significantly different from the mean serum level of
      TSH in the control group (3.26+/-2.11 mIU/L, p=0.772). Four individuals in the
      patient group and only 1 in the control group had a positive tuberculin skin
      test. CONCLUSION: Granuloma annulare patients are better to be assessed for
      diabetes mellitus, but the relationship between this skin disease and thyroid
      disorders or tuberculin skin test still needs to be investigated.

PMID- 28490897
TI  - Glutathione and its antiaging and antimelanogenic effects.
AB  - BACKGROUND: Previous studies showed that supplementation of reduced form of
      glutathione (GSH, 500 mg/d) has a skin-lightening efficacy in humans. This study
      was designed to evaluate the influences of both GSH and oxidized form (GSSG), at
      doses lower than 500 mg/d, on improving skin properties. PATIENTS AND METHODS: A
      randomized, double-blind, placebo-controlled, parallel, three-arm study was
      conducted. Healthy female subjects were equally randomized into three groups and
      took GSH (250 mg/d), GSSG (250 mg/d), or placebo orally for 12 weeks. At each
      visit at baseline and for 12 weeks, skin features including melanin index,
      wrinkles, and other relevant biophysical properties were measured. Blood samples
      were collected for safety monitoring. RESULTS: In generalized estimating equation
      analyses, melanin index and ultraviolet spots of all sites including face and arm
      when given GSH and GSSG tended to be lower than placebo. At some sites evaluated,
      subjects who received GSH showed a significant reduction in wrinkles compared
      with those taking placebo. A tendency toward increased skin elasticity was
      observed in GSH and GSSG compared with placebo. There were no serious adverse
      effects throughout the study. CONCLUSION: We showed that oral glutathione, 250
      mg/d, in both reduced and oxidized forms effectively influences skin properties.
      Overall, glutathione in both forms are well tolerated.

PMID- 28490898
TI  - Education and screening for chronic kidney disease in Indian youth: pilot program
      results.
AB  - BACKGROUND: There is a paucity of information on kidney education and screening
      programs in Indian youth. METHODS: Participants (n=2,158) from Chennai colleges
      were educated about the kidneys and chronic kidney disease (CKD) and screened in
      a pilot program from April to May 2013. This entailed: 1) a presentation and
      educational video and 2) an on-site assessment of weight, blood pressure, and
      demographic information. Urinalysis (UA) kits were distributed and returned in
      <=48 hours. We examined participant characteristics and their association with
      dipstick proteinuria using logistic regression. RESULTS: The mean (standard
      deviation [SD]) age was 18.9 (1.6) years, and 1,451 (68%) were men. Mean (SD)
      body mass index (BMI) was 21.9 (4.3) kg/m2; 745 (36%) had a BMI consistent with
      being overweight or obese. Mean (SD) systolic blood pressure (SBP) was 118.7
      (13.1) mm Hg, and 94 (5%) of the participants had SBP >=140. Mean (SD) diastolic
      blood pressure (DBP) was 70.9 (11.4) mm Hg, with 119 participants (6%) having
      >=90 mm Hg. A total of 136 participants had glycosuria (UA>=1+) and 120 (6%) had
      proteinuria (UA>=1+). In unadjusted analyses, sex (odds ratio [OR]=1.64
      [confidence interval, CI 1.06-2.55]; p=0.026 men vs. women) and age (OR=1.13 per
      year [CI 1.01-1.26]; p=0.032) were significantly associated with proteinuria. In
      the analysis adjusted for age, sex, SBP, DBP, glycosuria, and BMI, age remained
      independently associated with higher odds for proteinuria (OR=1.14 per year [1.02
      1.29]; p=0.026). Males showed a trend of higher risk compared with women (OR=1.57
      [CI 1.00-2.50]; p=0.051). CONCLUSION: This education and screening pilot program
      in a population of college students offers unique opportunities for
      identification, education, and early intervention for CKD.

PMID- 28490899
TI  - The influence of clinical equipoise and patient preferences on outcomes of
      conservative manual interventions for spinal pain: an experimental study.
AB  - BACKGROUND: Expected pain relief from treatment is associated with positive
      clinical outcomes in patients with musculoskeletal pain. Less studied is the
      influence on outcomes related to the preference of patients and providers for a
      specific treatment. OBJECTIVES: We sought to determine how provider and patient
      preferences for a manual therapy intervention influenced outcomes in individuals
      with acutely induced low back pain (LBP). PARTICIPANTS AND METHODS: Pain-free
      participants were randomly assigned to one of two manual therapies (joint biased
      [JB] or constant touch [CT]) 48 hours after completing an exercise protocol to
      induce LBP. Expectations for pain relief and preferences for treatment were
      collected at baseline, prior to randomization. Pain relief was assessed using a
      100 mm visual analog scale. All study procedures were conducted in a private
      testing laboratory at the University of Florida campus. RESULTS: Sixty
      participants were included in this study. After controlling for preintervention
      pain intensity, the multivariate model included only preintervention pain
      (B=0.12, p=0.07) and provider preference (B=3.05, p<0.0001) and explained 35.8%
      of the variance in postintervention pain. When determining whether a participant
      met his or her expected pain relief, receiving an intervention from a provider
      with a strong preference for that intervention increased the odds of meeting a
      participant's expected pain relief 68.3 times (p=0.013) compared to receiving any
      intervention from a provider with no preference. Receiving JB intervention from
      any provider increased the odds of meeting expected relief 29.7 times (p=0.023).
      The effect of a participant receiving an intervention they preferred was retained
      in the model but did not meet the criteria for a significant contribution.
      CONCLUSION: Our primary findings were that participant and provider preferences
      for treatment positively influence pain outcomes in individuals with acutely
      induced LBP, and joint-biased interventions resulted in a greater chance of
      meeting participants' expected outcomes. This is contrary to our hypothesis that
      the interaction of receiving an intervention for which a participant had a
      preference would result in the best outcome.

PMID- 28490900
TI  - Complex management of a patient with refractory primary erythromelalgia lacking a
      SCN9A mutation.
AB  - A 41-year-old woman presented with burning and erythema in her extremities
      triggered by warmth and activity, which was relieved by applying ice. Extensive
      workup was consistent with adult-onset primary erythromelalgia (EM). Several
      pharmacological treatments were tried including local anesthetics, capsaicin,
      ziconotide, and dantrolene, all providing 24-48 hours of relief followed by
      symptom flare. Interventional therapies, including peripheral and sympathetic
      ganglion blocks, also failed. Thus far, clonidine and ketamine have been the only
      effective agents for our patient. Genetic testing was negative for an EM
      associated mutation in the SCN9A gene, encoding the NaV1.7 sodium channel,
      suggesting a mutation in an alternate gene.

PMID- 28490901
TI  - Breast cancer and amyloid bodies: is there a role for amyloidosis in cancer-cell
      dormancy?
AB  - Breast cancer and Alzheimer's disease (AD) are major causes of death in older
      women. Interestingly, breast cancer occurs less frequently in AD patients than in
      the general population. Amyloidosis, the aggregation of amyloid proteins to form
      amyloid bodies, plays a central role in the pathogenesis of AD and other human
      neuropathies by forming intracellular fibrillary proteins. Contrary to popular
      belief, amyloidosis is a common occurrence in mammalian cells, and has recently
      been reported to be a natural physiological process in response to environmental
      stress stimulations (such as pH and temperature extremes, hypoxia, and oxidative
      stress). Many proteins contain an intrinsic "amyloid-converting motif", which
      acts in conjunction with a specific noncoding RNA to induce formation of
      proteinaceous amyloid bodies that are stored in intracellular bundles. In cancer
      cells such as breast and prostate, the process of amyloidosis induces cells to
      enter a dormant or resting stage devoid of cell division and proliferation.
      Therefore, cancer cells undergo growth cessation and enter a dormant stage
      following amyloidosis in the cell; this is akin to giving the cell AD to cease
      growth.

PMID- 28490902
TI  - Patient and physician preferences for anticancer drugs for the treatment of
      metastatic colorectal cancer: a discrete-choice experiment.
AB  - OBJECTIVE: Many publications describe preferences for colorectal cancer (CRC)
      screening; however, few studies elicited preferences for anticancer-drug
      treatment for metastatic CRC (mCRC). This study was designed to elicit
      preferences and risk tolerance among patients and oncologists in the USA for
      anticancer drugs to treat mCRC. MATERIALS AND METHODS: Patients aged 18 years or
      older with a self-reported diagnosis of mCRC and board-certified (or equivalent)
      oncologists who had treated patients with mCRC were recruited by two survey
      research companies from existing online patient panels in the USA. Additional
      oncologists were recruited from a list of US physicians. Patients and oncologists
      completed a discrete-choice experiment (DCE) survey. DCEs offer a systematic
      method of eliciting preferences and quantifying both the relative importance of
      treatment attributes and the tradeoffs respondents are willing to make among
      benefits and risks. Treatment attributes in the DCE were progression-free
      survival (PFS) and risks of severe papulopustular rash, serious hemorrhage,
      cardiopulmonary arrest, and gastrointestinal perforation. Patients' and
      physicians' maximum levels of acceptable treatment-related risks for two
      prespecified increases in efficacy were estimated. RESULTS: A total of 127
      patients and 150 oncologists completed the survey. Relative preferences for the
      treatment attributes in the study were mostly consistent with the expectation
      that better clinical outcomes were preferred over worse clinical outcomes. Risk
      tolerance varied between patients and physicians. On average, physicians were
      willing to tolerate higher risks than patients, although these differences were
      mostly not statistically significant. Post hoc latent-class analyses revealed
      that some patients and physicians were unwilling to forgo any efficacy to avoid
      toxicities, while others were willing to make such tradeoffs. CONCLUSION:
      Differences in preferences between patients and physicians suggest that there is
      the potential for improvement in patients' well-being. Initiating or enhancing
      discussions about patient tolerance for toxicities, such as skin rash and
      gastrointestinal perforations, may help prescribe treatments that entail more
      appropriate benefit-risk tradeoffs.

PMID- 28490903
TI  - Cardiovascular risks in smokers treated with nicotine replacement therapy: a
      historical cohort study.
AB  - BACKGROUND: Previous research suggests exposure to nicotine replacement therapy
      (NRT) may be associated with an increased risk of cardiovascular disease (CVD).
      METHODS: Using data from the United Kingdom's Clinical Practice Research
      Datalink, this study aimed to evaluate CVD events and survival among individuals
      who attempted smoking cessation with the support of NRT compared with those aided
      by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in
      50,214 smokers attempting to quit - 33,476 supported by smoking cessation advice
      and 16,738 with the support of NRT prescribed by their primary care physician.
      Patients were matched (2 smoking cessation advice patients:1 NRT patient) on
      demographic and clinical characteristics during a baseline year preceding their
      quit attempt. Cox proportional hazard regression, conditional negative binomial
      regression model, and conditional logistic regression were used to analyze data.
      RESULTS: Mean (standard deviation) population age was 47 (11.2) years; 51% were
      females. Time to first diagnosis of ischemic heart disease (IHD) among NRT and
      smoking cessation advice patients was similar within the first 4 weeks, but
      shorter for NRT patients over 52 weeks (hazard ratio [HR]: 1.35, 95% confidence
      interval [CI]: 1.03-1.77). A similar trend was observed for cerebrovascular
      disease (HR: 1.54, 95% CI: 1.08-2.19). NRT patients with a prior diagnosis of IHD
      or cerebrovascular disease had a higher rate of primary or secondary care
      consultations for IHD or cerebrovascular disease by 52 weeks (rate ratio: 1.50,
      95% CI: 1.14-1.99). Patients prescribed NRT had a shorter survival time over 52
      weeks, compared with those receiving advice only (HR: 1.39, 95% CI: 1.09-1.76).
      CONCLUSION: Our findings suggest that treatment with NRT over 4 weeks does not
      appear to have an impact on cardiovascular risks. However, a longer follow-up
      period of 52 weeks resulted in an increase in cardiovascular events for patients
      prescribed NRT, compared with those receiving smoking cessation advice only.

PMID- 28490904
TI  - Clinical epidemiology in the era of big data: new opportunities, familiar
      challenges.
AB  - Routinely recorded health data have evolved from mere by-products of health care
      delivery or billing into a powerful research tool for studying and improving
      patient care through clinical epidemiologic research. Big data in the context of
      epidemiologic research means large interlinkable data sets within a single
      country or networks of multinational databases. Several Nordic, European, and
      other multinational collaborations are now well established. Advantages of big
      data for clinical epidemiology include improved precision of estimates, which is
      especially important for reassuring ("null") findings; ability to conduct
      meaningful analyses in subgroup of patients; and rapid detection of safety
      signals. Big data will also provide new possibilities for research by enabling
      access to linked information from biobanks, electronic medical records, patient
      reported outcome measures, automatic and semiautomatic electronic monitoring
      devices, and social media. The sheer amount of data, however, does not eliminate
      and may even amplify systematic error. Therefore, methodologies addressing
      systematic error, clinical knowledge, and underlying hypotheses are more
      important than ever to ensure that the signal is discernable behind the noise.

PMID- 28490905
TI  - Reproductive and hormonal risk factors of breast cancer: a historical
      perspective.
AB  - The complexity of breast cancer etiology has puzzled scientists for more than 300
      years. In this brief review, we emphasize the importance of reproductive and
      hormonal factors in relation to the risk of breast cancer. By following the
      historical course of how various risk factors have been determined, this study
      attempts to illustrate the origin of hypotheses, their subsequent rejection, and
      development of new hypotheses. Starting with the contributions of Italian
      physicians in the 18th century and covering the activity of British
      epidemiologists before World War II, this review ends up with the international
      collaboration that became increasingly important in the second half of the 20th
      century.

PMID- 28490906
TI  - In vivo antiplasmodial activity evaluation of the leaves of Balanites
      rotundifolia (Van Tiegh.) Blatter (Balanitaceae) against Plasmodium berghei.
AB  - Balanites rotundifolia (BR) (Van Tiegh.) Blatter (Balanitaceae) has been used in
      Ethiopian folk medicine to treat malaria, despite the lack of scientific
      validation. Therefore, the present study was carried out to evaluate the
      antiplasmodial activity of 80% methanol leaf extract of BR in mice. Both the 4
      day suppressive test and Rane's test were employed. Three extract doses (BR100
      mg/kg, BR200 mg/kg, and BR400 mg/kg/d) were given orally, and chloroquine was the
      standard drug administered through the same route. Outcome measures for
      evaluating antiplasmodial efficacy were parasitemia level, packed cell volume,
      survival time, and body temperature as well as body weight change. Moreover,
      preliminary phytochemical and acute toxicity studies were carried out. With the 4
      day suppressive test, BR demonstrated dose-dependent significant reduction in
      parasitemia level at all test doses compared to the negative control: BR400 (67%,
      P<0.001), BR200 (42%, P<0.01), and BR100 (37%, P<0.05). With Rane's test as well,
      BR significantly (P<0.001 for all test doses) reduced the parasitemia level by
      38% (BR100), 45% (BR200), and 69% (BR400) in comparison to vehicle treatment. The
      crude extract was estimated to have oral median lethal dose higher than 2,000
      mg/kg, and the presence of alkaloids and cardiac glycosides was confirmed.
      Therefore, this study for the first time validated the antiplasmodial activity of
      crude leaf extract of BR. Further investigations for isolating specific
      phytochemicals and elucidating mechanisms are needed to address the quest for
      novel antimalarial drugs.

PMID- 28490907
TI  - Perspective on the Rezum(r) System: a minimally invasive treatment strategy for
      benign prostatic hyperplasia using convective radiofrequency water vapor thermal
      therapy.
AB  - Convective radiofrequency (RF) water vapor thermal therapy is a minimally
      invasive office or outpatient procedure for the treatment of bothersome moderate
      to-severe lower urinary tract symptoms associated with benign prostatic
      hyperplasia (BPH). It provides an option for patients seeking rapid and durable
      relief of urinary symptoms, improved quality of life, and preservation of sexual
      function as an alternative to long-term use of drugs and avoidance of the
      potential side effects of pharmaceuticals or invasive BPH surgery. The procedure
      is also applicable for the treatment of the median lobe or elevated bladder neck
      from central zone hyperplasia. This perspective presents a comprehensive overview
      of the Rezum(r) System convective RF thermal therapy device, the principles upon
      which it is based, the operative procedure, and the clinical evidence accrued to
      this point in time.

PMID- 28490908
TI  - Effects of prophylactic ankle and knee braces on leg stiffness during hopping.
AB  - During human movement, the leg can be represented as a mechanical spring, with
      its stiffness potentially contributing to sports performance and injury
      prevention. Although many individuals perform athletic activities with joint
      stabilizers, little is known about the effects of prophylactic lower extremity
      braces on leg stiffness. The objective of this study was to investigate the
      effect of ankle and/or knee braces on leg stiffness measured during one-legged
      hopping at a range of frequencies. Thirteen male participants performed one
      legged hopping with their dominant leg at frequencies of 2.2, 2.6, and 3.0 Hz.
      All participants were randomly tested under the following four brace conditions:
      1) no brace (control), 2) prophylactic ankle brace, 3) prophylactic knee brace,
      and 4) prophylactic ankle and knee braces. Based on a spring-mass model, leg
      stiffness was calculated using data from an accelerometer. It was found that leg
      stiffness increased with increasing hopping frequency for each brace condition.
      However, there were no significant differences in leg stiffness among the four
      brace conditions at the three hopping frequencies. Since some level of leg
      stiffness is needed for optimal athletic performance and training, these results
      suggest that ankle and knee braces do not significantly interfere with dynamic
      hopping activities.

PMID- 28490909
TI  - Determining early referral criteria for patients with suspected inflammatory
      arthritis presenting to primary care physicians: a cross-sectional study.
AB  - OBJECTIVE: Early diagnosis and initiation of treatment for inflammatory arthritis
      can greatly improve patient outcome. We aimed to provide standardized and
      validated criteria for use by primary care physicians (PCPs) in the
      identification of individuals requiring referral to a rheumatologist. PATIENTS
      AND METHODS: We analyzed the predictive value of a wide variety of demographic
      variables, patient-reported complaints, physical examination results, and
      biomarkers in order to identify the most useful factors for indicating a
      requirement for referral. Patients for this cross-sectional study were enrolled
      from various centers of the city of Jeddah, Saudi Arabia, if they were >=18 years
      of age and presented to a PCP with small joint pain that had been present for
      more than 6 weeks. A total of 203 patients were enrolled, as indicated by the
      sample size calculation. Each patient underwent a standardized physical
      examination, which was subsequently compared to ultrasound findings. Biomarker
      analysis and a patient interview were also carried out. Results were then
      correlated with the final diagnosis made by a rheumatologist. RESULTS: A total of
      9 variables were identified as having high specificity and good predictive value:
      loss of appetite, swelling of metacarpophalangeal joint 2 or 5, swelling of
      proximal inter-phalangeal joint 2 or 3, wrist swelling, wrist tenderness, a
      positive test for rheumatoid factor, and a positive test for anti-citrullinated
      protein antibodies. CONCLUSION: Nine variables should be the basis of early
      referral criteria. It should aid PCPs in making appropriate early referrals of
      patients with suspected inflammatory arthritis, accelerating diagnosis and
      initiation of treatment.

PMID- 28490911
TI  - The effect of physical activity on sleep quality, well-being, and affect in
      academic stress periods.
AB  - The stress-buffering hypothesis postulates that physical activity and exercise
      can buffer the negative effects of (academic) stress on health. It still remains
      an open question whether students, who regularly engage in physical activity and
      exercise within their academic examination period, can successfully diminish
      these negative effects. Sixty-four subjects participated in this study and
      completed a total of five surveys, with T1 at the end of the semester break
      (baseline) and T2-T5 being presented every Friday in the last 4 weeks of the
      semester (examination period). They were asked to answer questions about their
      activity level, sleep quality, well-being and affect. Hierarchical linear models
      showed significant dependencies on time for all dependent measures. The expansion
      of the model for exercise also showed significant main effects of this predictor
      on well-being and positive affect (PA) and negative affect. Moreover, significant
      interactions with time for sleep quality and PA were found. Results suggest that
      physical activity and exercise in the academic examination period may be able to
      buffer the negative effects of stress on health-related outcomes. Therefore,
      activity levels should be maintained in times of high stress to prevent negative
      effects on sleep, well-being and affect in students.

PMID- 28490910
TI  - Optimizing psychosocial interventions in first-episode psychosis: current
      perspectives and future directions.
AB  - Psychotic-spectrum disorders such as schizophrenia, schizoaffective disorder, and
      bipolar disorder with psychotic features are devastating illnesses accompanied by
      high levels of morbidity and mortality. Growing evidence suggests that outcomes
      for individuals with psychotic-spectrum disorders can be meaningfully improved by
      increasing the quality of mental health care provided to these individuals and
      reducing the delay between the first onset of psychotic symptoms and the receipt
      of adequate psychiatric care. More specifically, multicomponent treatment
      packages that 1) simultaneously target multiple symptomatic and functional needs
      and 2) are provided as soon as possible following the initial onset of psychotic
      symptoms appear to have disproportionately positive effects on the course of
      psychotic-spectrum disorders. Yet, despite the benefit of multicomponent care for
      first-episode psychosis, clinical and functional outcomes among individuals with
      first-episode psychosis participating in such services are still suboptimal.
      Thus, the goal of this review is to highlight putative strategies to improve care
      for individuals with first-episode psychosis with specific attention to
      optimizing psychosocial interventions. To address this goal, we highlight four
      burgeoning areas of research with regard to optimization of psychosocial
      interventions for first-episode psychosis: 1) reducing the delay in receipt of
      evidence-based psychosocial treatments; 2) synergistic pairing of psychosocial
      interventions; 3) personalized delivery of psychosocial interventions; and 4)
      technological enhancement of psychosocial interventions. Future research on these
      topics has the potential to optimize the treatment response to evidence-based
      psychosocial interventions and to enhance the improved (but still suboptimal)
      treatment outcomes commonly experienced by individuals with first-episode
      psychosis.

PMID- 28490912
TI  - Update on the treatment of narcolepsy: clinical efficacy of pitolisant.
AB  - Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is
      characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals
      with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle
      tone that is triggered by positive or negative emotions. Narcolepsy decreases the
      quality of life of the afflicted individuals. Currently used drugs treat EDS
      alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone
      ("off-label" use of antidepressants), or both EDS and cataplexy (sodium oxybate).
      These drugs have abuse, tolerability, and adherence issues. A greater diversity
      of drug options is needed to treat narcolepsy. The small molecule drug,
      pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus
      increasing histaminergic tone in the wake promoting system of the brain.
      Pitolisant has been studied in animal models of narcolepsy and used in clinical
      trials as a treatment for narcolepsy. A comprehensive search of online databases
      (eg, Medline, PubMed, EMBASE, the Cochrane Library Database, Ovid MEDLINE, Europe
      PubMed Central, EBSCOhost CINAHL, ProQuest Research Library, Google Scholar, and
      ClinicalTrials.gov) was performed. Nonrandomized and randomized studies were
      included. This review focuses on the outcomes of four clinical trials of
      pitolisant to treat narcolepsy. These four trials show that pitolisant is an
      effective drug to treat EDS and cataplexy in narcolepsy.

PMID- 28490913
TI  - Health-related quality of life among cognitively intact nursing home residents
      with and without cancer - a 6-year longitudinal study.
AB  - BACKGROUND: Limited information exists regarding the natural development of
      health-related quality of life (HRQOL) and its determinants among mentally intact
      nursing home (NH) residents. We aimed to examine HRQOL over time during a 6-year
      period among residents of NHs, who are not cognitively impaired, and to examine
      whether sense of coherence and a diagnosis of cancer influence HRQOL. METHODS:
      The study was prospective and included baseline assessment and 6-year follow-up.
      After baseline assessment of 227 cognitively intact NH residents (Clinical
      Dementia Rating score <= 0.5), we interviewed 52 living respondents a second time
      at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up.
      We recorded data from the interviews using the Short Form-36 (SF-36) Health
      Survey and the Sense of Coherence Scale. To study different developments over
      time for residents without and with cancer, we tested interactions between cancer
      and time. RESULTS: The subscores of physical functioning and role limitation
      physical domains declined with time (P < 0.001 and P = 0.02, respectively).
      Having a diagnosis of cancer at baseline was negatively correlated with general
      health (P = 0.002). Sense of coherence at baseline was positively correlated with
      all the SF-36 subscores from baseline to follow-up (P < 0.001). CONCLUSION: The
      study indicates that the HRQOL changed over time during the 6 years of follow-up,
      and the sense of coherence appeared to be an important component of the HRQOL.
      Finally, our results showed that having a diagnosis of cancer was associated with
      decline in the general health subdimension.

PMID- 28490914
TI  - Assessment of residency program outcomes via alumni surveys.
AB  - BACKGROUND: One trend in medical education is outcomes-oriented training.
      Outcomes usually refer to individuals' acquisition of competencies, for example,
      during training in residency programs. However, little is known about outcomes of
      these programs. In order to fill this gap, human resource (HR) data were analyzed
      and alumni of a pediatric residency program were surveyed at the Department of
      Pediatrics, Bern University Hospital, Switzerland. METHODS: Residency program
      outcomes (demographics, career choices, part-time or full-time work status,
      competencies, feedback) were assessed through in-house HR databases, publicly
      available data on the Internet (physician directory and practice homepages), and
      2 alumni surveys (S1, S2). RESULTS: In all, 109 alumni met the inclusion
      criteria. Retention rate at the hospital was low (14%). Forty-six alumni (42%) in
      private practice were eligible for alumni surveys. Response rates were 87% (S1)
      and 61% (S2). Time intervals between 2 career decisions (selecting specialty of
      pediatrics vs selecting setting of private practice) varied widely (late-training
      decision to enter private practice). Mean employment level in private practice
      was 60% (range 20%-100%). Most valued rotation was emergency medicine; most
      desired competencies in future colleagues were the ability to work in a team,
      proficiency in pediatrics, and working economically. CONCLUSION: A broadened view
      on outcomes - beyond individuals' competency acquisition - provides informative
      insights into a training program, can allow for informed program updates, and
      guide future program development.

PMID- 28490915
TI  - Older patients have increased risk of poor outcomes after low-velocity pedestrian
      motor vehicle collisions.
AB  - BACKGROUND: Motor vehicle collisions (MVCs) are a leading cause of injury in the
      US. While the probability of collision with a pedestrian (PMVC) has declined in
      recent years, the probability of a pedestrian fatality has risen. Our objective
      was to determine whether older age impacts potential outcomes in patients
      involved in low-velocity PMVCs. MATERIALS AND METHODS: We performed a
      retrospective-cohort study of adult patients aged >14 years involved in low
      velocity pedestrian-MVCs (<15 miles per hour [24.14 km/h]), presenting to an
      urban level I trauma center from January to November 2013. Subjects were
      identified via trauma registry and stratified: ages 15-49 years and >=50 years.
      Electronic medical records were reviewed for demographics, vital signs, and
      laboratory results on initial presentation, presence or absence of systemic
      inflammatory response syndrome (SIRS), shock index (SI), injury-severity score
      (ISS), length of stay (LOS), and survival to discharge. For statistical analysis,
      chi2 or Student's t-tests were utilized. RESULTS: Our study included 145 patients
      (77 female) with a mean age of 41.9+/-3 years; 95 patients were aged 15-49 years
      (mean 31.9+/-2.2 years), and 50 patients were aged >=50 years or older (mean
      62.44+/-2.9 years). Mean ISS was 10.05+/-1.95, mean SI was 0.68+/-0.03, and mean
      LOS was 3.67+/-0.57 days. A total of 41 patients met SIRS criteria on arrival,
      and nine patients expired (6.2%). Mean ISS (15.64+/-4.42 vs 7.1+/-1.64, P<0.001)
      and mean SI (0.75+/-0.07 vs 0.65+/-0.03, P=0.002) were higher in patients aged
      >=50 years. Mean LOS was longer in older patients (5.22+/-1.14 vs 2.85+/-0.58
      days, P<0.001). Older age was associated with SIRS on arrival (P=0.023) and
      associated with mortality (P=0.004). CONCLUSION: Age >=50 years is associated
      with greater severity of injury and poor outcomes for patients involved in low
      velocity PMVCs. Increased clinical attention and resource allocation should be
      directed toward older patients after low-velocity PMVCs.

PMID- 28490916
TI  - The cannabis withdrawal syndrome: current insights.
AB  - The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders
      (CUDs) (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition)
      and cannabis dependence (International Classification of Diseases [ICD]-10).
      Several lines of evidence from animal and human studies indicate that cessation
      from long-term and regular cannabis use precipitates a specific withdrawal
      syndrome with mainly mood and behavioral symptoms of light to moderate intensity,
      which can usually be treated in an outpatient setting. Regular cannabis intake is
      related to a desensitization and downregulation of human brain cannabinoid 1
      (CB1) receptors. This starts to reverse within the first 2 days of abstinence and
      the receptors return to normal functioning within 4 weeks of abstinence, which
      could constitute a neurobiological time frame for the duration of CWS, not taking
      into account cellular and synaptic long-term neuroplasticity elicited by long
      term cannabis use before cessation, for example, being possibly responsible for
      cannabis craving. The CWS severity is dependent on the amount of cannabis used
      pre-cessation, gender, and heritable and several environmental factors.
      Therefore, naturalistic severity of CWS highly varies. Women reported a stronger
      CWS than men including physical symptoms, such as nausea and stomach pain.
      Comorbidity with mental or somatic disorders, severe CUD, and low social
      functioning may require an inpatient treatment (preferably qualified detox) and
      post-acute rehabilitation. There are promising results with gabapentin and delta
      9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be
      beneficial to treat CWS insomnia. According to small studies, venlafaxine can
      worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone,
      and divalproex had no relevant effect. Certainly, further research is required
      with respect to the impact of the CWS treatment setting on long-term CUD
      prognosis and with respect to psychopharmacological or behavioral approaches,
      such as aerobic exercise therapy or psychoeducation, in the treatment of CWS. The
      up-to-date ICD-11 Beta Draft is recommended to be expanded by physical CWS
      symptoms, the specification of CWS intensity and duration as well as gender
      effects.

PMID- 28490918
TI  - The two solitudes of primary care and cancer specialist care: is there a bridge?

PMID- 28490919
TI  - Clinician participation in CADTH's pan-Canadian Oncology Drug Review:
      contribution and impact on cancer drug funding recommendations.

PMID- 28490917
TI  - From caveman companion to medical innovator: genomic insights into the origin and
      evolution of domestic dogs.
AB  - The phenotypic and behavioral diversity of the domestic dog has yet to be matched
      by any other mammalian species. In their current form, which comprises more than
      350 populations known as breeds, there is a size range of two orders of magnitude
      and morphological features reminiscent of not only different species but also
      different phylogenetic families. The range of both appearance and behavior found
      in the dog is the product of millennia of human interference, and though humans
      created the diversity it remains a point of fascination to both lay and
      scientific communities. In this review we summarize the current understanding of
      the history of dog domestication based on molecular data. We will examine the
      ways that canine genetic and genomic studies have evolved and look at examples of
      dog genetics in the light of human disease.

PMID- 28490920
TI  - The role of family physicians in cancer care: perspectives of primary and
      specialty care providers.
AB  - BACKGROUND: Currently, the specific role of family physicians (fps) in the care
      of people with cancer is not well defined. Our goal was to explore physician
      perspectives and contextual factors related to the coordination of cancer care
      and the role of fps. METHODS: Using a constructivist grounded theory approach, we
      conducted telephone interviews with 58 primary and cancer specialist health care
      providers from across Canada. RESULTS: The participants-21 fps, 15 surgeons, 12
      medical oncologists, 6 radiation oncologists, and 4 general practitioners in
      oncology-were asked to describe both the role that fps currently play and the
      role that, in their opinion, fps should play in the future care of cancer
      patients across the cancer continuum. Participants identified 3 key roles:
      coordinating cancer care, managing comorbidities, and providing psychosocial care
      to patients and their families. However, fps and specialists discussed many
      challenges that prevent fps from fully performing those roles: ? The fps
      described communication problems resulting from not being kept "in the loop"
      because they weren't copied on patient reports and also the lack of clearly
      defined roles for all the various health care providers involved in providing
      care to cancer patients.? The specialists expressed concerns about a lack of
      patient access to fp care, leaving specialists to fill the care gaps. The fps and
      specialists both recommended additional training and education for fps in
      survivorship care, cancer screening, genetic testing, and new cancer treatments.
      CONCLUSIONS: Better communication, more collaboration, and further education are
      needed to enhance the role of fps in the care of cancer patients.

PMID- 28490921
TI  - Use of physician services during the survivorship phase: a multi-province study
      of women diagnosed with breast cancer.
AB  - INTRODUCTION: Oncologists have traditionally been responsible for providing
      routine follow-up care for cancer survivors; in recent years, however, primary
      care providers (pcps) are taking a greater role in care during the follow-up
      period. In the present study, we used a longitudinal multi-province retrospective
      cohort study to examine how primary care and specialist care intersect in the
      delivery of breast cancer follow-up care. METHODS: Various databases (registry,
      clinical, and administrative) were linked in each of four provinces: British
      Columbia, Manitoba, Ontario, and Nova Scotia. Population-based cohorts of breast
      cancer survivors were identified in each province. Physician visits were
      identified using billings or claims data and were classified as visits to primary
      care (total, breast cancer-specific, and other), oncology (medical oncology,
      radiation oncology, and surgery), and other specialties. The mean numbers of
      visits by physician type and specialty, or by combinations thereof, were
      examined. The mean numbers of visits for each follow-up year were also examined
      by physician type. RESULTS: The results showed that many women (>64%) in each
      province received care from both primary care and oncology providers during the
      follow-up period. The mean number of breast cancer-specific visits to primary
      care and visits to oncology declined with each follow-up year. Interprovincial
      variations were observed, with greater surgeon follow-up in Nova Scotia and
      greater primary care follow-up in British Columbia. Provincial differences could
      reflect variations in policies and recommendations, relevant initiatives, and
      resources or infrastructure to support pcp-led follow-up care. CONCLUSIONS:
      Optimizing the role of pcps in breast cancer follow-up care might require
      strategies to change attitudes about pcp-led follow-up and to better support pcps
      in providing survivorship care.

PMID- 28490922
TI  - A population-based assessment of primary care visits during adjuvant chemotherapy
      for breast cancer.
AB  - BACKGROUND: We used administrative health data to explore the impact of primary
      care physician (pcp) visits on acute-care service utilization by women receiving
      adjuvant chemotherapy for early-stage breast cancer (ebc). METHODS: Our
      population-based retrospective cohort study examined pcp visits and acute-care
      use [defined as an emergency room (er) visit or hospitalization] by women
      diagnosed with ebc between 2007 and 2009 and treated with adjuvant chemotherapy.
      Multivariate regression analysis was used to identify the effect of pcp visits on
      the likelihood of experiencing an acute-care visit. RESULTS: Patients receiving
      chemotherapy visited a pcp significantly more frequently than they had before
      their diagnosis [relative risk (rr): 1.48; 95% confidence interval (ci): 1.44 to
      1.53; p < 0.001] and significantly more frequently than control subjects without
      cancer (rr: 1.51; 95% ci: 1.46 to 1.57; p < 0.001). More than one third of pcp
      visits by chemotherapy patients were related to breast cancer or chemotherapy
      related side effects. In adjusted multivariate analyses, the likelihood of
      experiencing an er visit or hospitalization increased in the days immediately
      after a pcp visit (rr: 1.92; 95% ci: 1.76 to 2.10; p < 0.001). CONCLUSIONS:
      During chemotherapy treatment, patients visited their pcp more frequently than
      control subjects did, and they visited for reasons related to their breast cancer
      or to chemotherapy-related side effects. Visits to a pcp by patients receiving
      chemotherapy were associated with an increased frequency of er visits or
      hospitalizations in the days immediately after the pcp visit. Those results
      suggest an opportunity to institute measures for early detection and intervention
      in chemotherapy side effects.

PMID- 28490923
TI  - Multigene expression profile testing in breast cancer: is there a role for family
      physicians?
AB  - BACKGROUND: Family physicians (fps) play a role in aspects of personalized
      medicine in cancer, including assessment of increased risk because of family
      history. Little is known about the potential role of fps in supporting cancer
      patients who undergo tumour gene expression profile (gep) testing. METHODS: We
      conducted a mixed-methods study with qualitative and quantitative components.
      Qualitative data from focus groups and interviews with fps and cancer specialists
      about the role of fps in breast cancer gep testing were obtained during studies
      conducted within the pan-Canadian canimpact research program. We determined the
      number of visits by breast cancer patients to a fp between the first medical
      oncology visit and the start of chemotherapy, a period when patients might be
      considering results of gep testing. RESULTS: The fps and cancer specialists felt
      that ordering gep tests and explaining the results was the role of the
      oncologist. A new fp role was identified relating to the fp-patient relationship:
      supporting patients in making adjuvant therapy decisions informed by gep tests by
      considering the patient's comorbid conditions, social situation, and preferences.
      Lack of fp knowledge and resources, and challenges in fp-oncologist communication
      were seen as significant barriers to that role. Between 28% and 38% of patients
      visited a fp between the first oncology visit and the start of chemotherapy.
      CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients
      who are making adjuvant treatment decisions after receiving the results of gep
      testing. For success in this new role, education and point-of-care tools,
      together with more effective communication strategies between fps and
      oncologists, are needed.

PMID- 28490924
TI  - Improving molecular testing and personalized medicine in non-small-cell lung
      cancer in Ontario.
AB  - BACKGROUND: Although molecular testing has become standard in managing advanced
      nonsquamous non-small-cell lung cancer (nsclc), most patients undergo minimally
      invasive procedures, and the diagnostic tumour specimens available for testing
      are usually limited. A knowledge translation initiative to educate diagnostic
      specialists about sampling techniques and laboratory processes was undertaken to
      improve the uptake and application of molecular testing in advanced lung cancer.
      METHODS: A multidisciplinary panel of physician experts including pathologists,
      respirologists, interventional thoracic radiologists, thoracic surgeons, medical
      oncologists, and radiation oncologists developed a specialty-specific education
      program, adapting international clinical guidelines to the local Ontario context.
      Expert recommendations from the program are reported here. RESULTS: Panel experts
      agreed that specialists procuring samples for lung cancer diagnosis should choose
      biopsy techniques that maximize tumour cellularity, and that conservation
      strategies to maximize tissue for molecular testing should be used in tissue
      processing. The timeliness of molecular reporting can be improved by pathologist
      initiated reflex testing upon confirmation of nonsquamous nsclc and by prompt
      transportation of specimens to designated molecular diagnostic centres. To
      coordinate timely molecular testing and optimal treatment, collaboration and
      communication between all clinicians involved in diagnosing patients with
      advanced lung cancer are mandatory. CONCLUSIONS: Knowledge transfer to diagnostic
      lung cancer specialists could potentially improve molecular testing and treatment
      for advanced lung cancer patients.

PMID- 28490926
TI  - Challenges and insights in implementing coordinated care between oncology and
      primary care providers: a Canadian perspective.
AB  - We report here on the current state of cancer care coordination in Canada and
      discuss challenges and insights with respect to the implementation of
      collaborative models of care. We also make recommendations for future research.
      This work is based on the findings of the Canadian Team to Improve Community
      Based Cancer Care Along the Continuum (canimpact) casebook project. The casebook
      project identified models of collaborative cancer care by systematically
      documenting and analyzing Canadian initiatives that aim to improve or enhance
      care coordination between primary care providers and oncology specialists. The
      casebook profiles 24 initiatives, most of which focus on breast or colorectal
      cancer and target survivorship or follow-up care. Current key challenges in
      cancer care coordination are associated with establishing program support,
      engaging primary care providers in the provision of care, clearly defining
      provider roles and responsibilities, and establishing effective project or
      program planning and evaluation. Researchers studying coordinated models of
      cancer care should focus on designing knowledge translation strategies with
      updated and refined governance and on establishing appropriate protocols for both
      implementation and evaluation.

PMID- 28490925
TI  - Management of EGFR-mutated non-small-cell lung cancer: practical implications
      from a clinical and pathology perspective.
AB  - Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have
      evolved from being histologically described to molecularly defined. Management of
      lung adenocarcinomas now generally requires multiple molecular tests at baseline
      to define the optimal treatment strategy. More recently, second biopsies
      performed at progression in patients treated with tyrosine kinase inhibitors
      (tkis) have further defined the continued use of molecularly targeted therapy. In
      the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For
      that patient population, multiple lines of tki therapy are now available either
      clinically or in clinical trials. Each line of treatment is guided by the
      specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We
      first describe the various mechanisms of acquired resistance to EGFR tki
      treatment. We then focus on strategies that clinicians and pathologists can both
      use during tissue acquisition and handling to optimize patient results. We also
      discuss future directions for the molecular characterization of lung cancers with
      driver mutations, including liquid biopsies. Finally, we provide an algorithm to
      guide treating physicians managing patients with EGFR-mutated nsclc. The same
      framework can also be applied to other molecularly defined nsclc subgroups as
      resistance patterns are elucidated and additional lines of treatment are
      developed.

PMID- 28490927
TI  - How different is cancer control across Canada? Comparing performance indicators
      for prevention, screening, diagnosis, and treatment.
AB  - Meaningful performance measures are an important part of the toolkit for health
      system improvement. The Canadian Partnership Against Cancer has been reporting on
      pan-Canadian cancer system performance indicators since 2009-work that has led to
      the availability of standardized measures that can help to shed light on the
      extent of variation and opportunities for quality improvement across the country.
      Those measures include a core set of system indicators ranging from prevention
      and screening, through diagnosis and treatment, to survivorship and end-of-life
      care. Key indicators were calculated and graphed, showing the range from worst to
      best result for the provinces and territories included in the data. There were
      often significant differences in cancer system performance between provinces and
      territories. For example, smoking prevalence rates ranged from 14% to 62%. The
      90th percentile wait times from an abnormal breast screen to resolution (without
      biopsy) ranged from 4 weeks to 8 weeks. The percentage of breast cancer
      resections that used breast-conserving surgery rather than mastectomy ranged from
      38% to 75%. Clinical trial participation rates for adults ranged from 0.2% to
      6.6%. Variations in performance indicators between Canadian jurisdictions suggest
      potential differences in the planning and delivery of cancer control services and
      in clinical practice patterns and patient outcomes. Understanding sources of
      variation can help to identify opportunities for improvements in the quality and
      outcomes of cancer control service delivery in each province and territory.

PMID- 28490928
TI  - Synthesis maps: visual knowledge translation for the CanIMPACT clinical system
      and patient cancer journeys.
AB  - Salient findings and interpretations from the canimpact clinical cancer research
      study are visually represented in two synthesis maps for the purpose of
      communicating an integrated presentation of the study to clinical cancer
      researchers and policymakers. Synthesis maps integrate evidence and expertise
      into a visual narrative for knowledge translation and communication. A clinical
      system synthesis map represents the current Canadian primary care and cancer
      practice systems, proposed as a visual knowledge translation from the mixed
      methods canimpact study to inform Canadian clinical research, policy, and
      practice discourses. Two synthesis maps, drawn together from multiple canimpact
      investigations and sources, were required to articulate critical differences
      between the clinical system and patient perspectives. The synthesis map of Canada
      wide clinical cancer systems illustrates the relationships between primary care
      and the full cancer continuum. A patient-centred map was developed to represent
      the cancer (and primary care) journeys as experienced by breast and colorectal
      cancer patients.

PMID- 28490929
TI  - Ovarian cancer in Manitoba: trends in incidence and survival, 1992-2011.
AB  - BACKGROUND: Because the International Cancer Benchmarking Partnership, in a study
      of diagnosis years between 1995 and 2007, showed lower-than-expected survival for
      Manitoba's ovarian cancer patients, we undertook an analysis to describe the
      features of ovarian cancer diagnosed in Manitoba during a 20-year period. We also
      determined the most recent trends in survival to see if the previous results were
      sustained. METHODS: In this retrospective cohort study, ovarian cancer cases
      diagnosed during 1992-2011 were extracted from the Manitoba Cancer Registry. The
      incidence of ovarian cancer was calculated for the overall group and for age,
      morphology, residence, treatment, and stage. Trends over time, with a particular
      focus on changes that might correlate with poor survival, were analyzed. The 1-
      and 3-year relative survival rates were also calculated. RESULTS: The incidence
      of ovarian cancer did not vary over time (p = 0.640), even when stratified by age
      or morphology groups. Use of adjuvant chemotherapy decreased (p = 0.005) and use
      of neoadjuvant chemotherapy increased over time (p = 0.002). Diagnoses of stage
      iv cancers declined over time (p < 0.020). Trends in incidence did not coincide
      with previously observed decreases in relative survival. CONCLUSIONS: A decline
      in diagnoses of stage iv ovarian cancer could be responsible for a recent
      increase in relative survival. However, sample size might have limited power in
      some analyses, and the previously reported decrease in relative survival might
      have been due to a random fluctuation in the data. Future efforts will focus on
      continued monitoring of the patterns of ovarian cancer presentation and outcomes
      in Manitoba.

PMID- 28490930
TI  - Metformin and breast cancer stage at diagnosis: a population-based study.
AB  - PURPOSE: The objective of the present study was to use a large, population-based
      cohort to examine the association between metformin and breast cancer stage at
      diagnosis while accounting for mammography differences. METHODS: We used data
      from Ontario administrative health databases to identify women 68 years of age or
      older with diabetes and invasive breast cancer diagnosed from 1 January 2007 to
      31 December 2012. Adjusted logistic regression models were used to compare breast
      cancer stage at diagnosis (stages i and ii vs. iii and iv) between the women
      exposed and not exposed to metformin. We also examined the association between
      metformin use and estrogen receptor status, tumour size, and lymph node status in
      the subset of women for whom those data were available. RESULTS: We identified
      3125 women with diabetes and breast cancer; 1519 (48.6%) had been exposed to
      metformin before their cancer diagnosis. Median age at breast cancer diagnosis
      was 76 years (interquartile range: 72-82 years), and mean duration of diabetes
      was 8.8 +/- 5.9 years. In multivariable analyses, metformin exposure was not
      associated with an earlier stage of breast cancer (odds ratio: 0.98; 95%
      confidence interval: 0.81 to 1.19). In secondary analyses, metformin exposure was
      not associated with estrogen receptor-positive breast cancer, tumours larger than
      2 cm, or positive lymph nodes. CONCLUSIONS: This population-based study did not
      show an association between metformin use and breast cancer stage or tumour
      characteristics at diagnosis. Our study considered older women with long-standing
      diabetes, and therefore further studies in younger patients could be warranted.

PMID- 28490931
TI  - Treatment and outcomes for glioblastoma in elderly compared with non-elderly
      patients: a population-based study.
AB  - PURPOSE: Elderly patients make up a large percentage of the individuals newly
      diagnosed with glioblastoma (gbm), but they face particular challenges in
      tolerating standard therapy, and compared with younger patients, they experience
      significantly shorter survival. We set out to compare clinical characteristics,
      treatment patterns, and outcomes in a non-elderly group (<65 years) and an
      elderly group (>=65 years) of patients diagnosed with gbm. METHODS: This
      retrospective population-based study used a province-wide cancer registry to
      identify patients with a new diagnosis of gbm within a 6-year period (2006-2012).
      Of the 138 patients identified, 56 (40.6%) were 65 years of age or older.
      Demographic characteristics, treatment patterns, and overall survival (os) in the
      elderly and non-elderly groups were compared. Predictors of os were determined
      using multivariate analysis. RESULTS: Elderly patients were more likely to
      present with a poor performance status (Eastern Cooperative Oncology Group >= 2),
      to undergo biopsy without resection, and to receive whole-brain or
      hypofractionated radiotherapy. Compared with non-elderly patients, the elderly
      patients were less likely to receive adjuvant temozolomide. Survival time was
      significantly shorter in the elderly than in the non-elderly patients (7.2 months
      vs. 11.2 months). In multivariate analysis, surgical resection, hypofractionated
      radiotherapy (compared with whole-brain or conventional radiotherapy), and
      chemotherapy were predictive of os in older patients. Among elderly patients
      receiving radiation, survival was improved with the use of combined therapy
      compared with the use of radiation only (11.3 months vs. 4.6 months).
      CONCLUSIONS: Overall survival was shorter for elderly patients with gbm than for
      non-elderly patients; the elderly patients were also less likely to receive
      intensive surgical or adjuvant therapy. Our population-based analysis
      demonstrated improved os with surgical resection, hypofractionated radiotherapy,
      and temozolomide, and supports the results of recent clinical trials
      demonstrating a benefit for combination chemoradiotherapy in older patients.

PMID- 28490932
TI  - Contextualizing the use of oncologic imaging within treatment phases: imaging
      trends and modality preferences, 2000-2014.
AB  - BACKGROUND: In the present study, we retrospectively evaluated the use of
      tomographic imaging in adult cancer patients to clarify how recent growth
      plateaus in the use of tomographic imaging in the United States might have
      affected oncologic imaging during the same period. METHODS: At a U.S. academic
      cancer centre, 12,059 patients with dates of death from January 2000 through
      December 2014 were identified. Imaging was restricted to brain and body computed
      tomography (ct), brain and body magnetic resonance (mr), and body positron
      emission tomography (pet) with and without superimposed ct. Trends during the
      staging (1 year after diagnosis), monitoring (18-6 months before death), and end
      of-life (final 6 months before death) phases were analyzed. RESULTS: Comparing
      the 2005-2009 with the 2010-2014 period, mean intensity of pet imaging increased
      21% during staging (p = 0.0000) and 27% during end of life (p = 0.0019). In the
      monitoring phase, mean intensity for ct brain, ct body, and mr body imaging
      decreased by 26% (p = 0.0133), 11% (p = 0.0118), and 26% (p = 0.0008),
      respectively. Aggregate mean intensity of imaging increased in the 13%-27% range
      every 3 months from 18 months before death to death, reaching 1.43 images in the
      final 3 months of life. Patients diagnosed in the final 18 months of life had an
      average of 1 additional image during both the 3 months after diagnosis (p =
      0.0000) and the final 3 months before death (p = 0.0000). CONCLUSIONS: Imaging
      increased as temporal proximity to death decreased, and patients diagnosed near
      death received more staging imaging, suggesting that imaging guidelines should
      consider imaging intensity within the context of treatment phase. Despite the
      development, by multiple organizations, of appropriateness criteria to reduce
      imaging utilization, aggregate per-patient imaging showed insignificant changes.
      Simultaneous fluctuations in the intensity of imaging by modality suggest recent
      changes in the modalities preferred by providers.

PMID- 28490933
TI  - Prognostic and predictive value of low estrogen receptor expression in breast
      cancer.
AB  - PURPOSE: Anti-hormonal therapy (tamoxifen) is recommended for estrogen receptor
      (er)-positive breast cancer (bca); however, its effect on low-receptor cancers is
      unclear. We retrospectively evaluated the effect of adjuvant tamoxifen in
      patients with weakly er-positive bca. METHODS: We identified 2221 bca patients
      who had been er-tested by ligand-based assay (lba) during 1976-1995 and who had
      been treated and followed until 2008. Cox proportional hazards models adjusted
      for age, body mass index, tumour size, nodal status, surgery, and chemotherapy
      were used to assess the effect of er level on bca survival in patients who
      received tamoxifen. RESULTS: Overall, 17% (383) of patients were within 0-3
      fmol/mg cytosol protein, and 12% (266) were within 4-9 fmol/mg cytosol protein.
      Patients with er levels of 0-3, 4-9, 10-19, 20-49, and 50 fmol/mg or more cytosol
      protein had 20-year bca survival rates of 56%, 56%, 63%, 71%, and 60%
      respectively. Of the 2221 patients studied, 661 (29.8%) received anti-hormonal
      therapy. Within the latter group, er levels of 0-3, 4-9, 10-19, 20-49, and 50
      fmol/mg or more cytosol protein were associated with a hazard ratio for lower bca
      mortality: respectively, 1.00 (reference), 0.59 (p = 0.09), 0.19 (p < 0.0001),
      0.26 (p < 0.0001), and 0.31 (p < 0.0001)-the risk reduction being significant
      only for er levels of 10 fmol/mg or more cytosol protein. CONCLUSIONS: Tamoxifen
      use in bca patients with a weakly positive er status (4-9 fmol/mg cytosol
      protein), compared with those having higher er levels (>=10 fmol/mg cytosol
      protein), is not associated with a significantly lower bca-specific mortality.
      Our results do not support treatment with anti-hormonal therapy for bca patients
      with a weakly positive er status as identified by lba.

PMID- 28490934
TI  - Factors influencing treatment selection and survival in advanced lung cancer.
AB  - PURPOSE: Despite numerous breakthrough therapies, inoperable lung cancer still
      places a heavy burden on patients who might not be candidates for chemotherapy.
      To identify potential candidates for the newly emerging immunotherapy-based
      treatment paradigms, we explored the clinical and biologic factors affecting
      treatment decisions. METHODS: We retrospectively reviewed the records of patients
      diagnosed at our university-affiliated cancer centre between 1 January 2011 and
      31 December 2013. Patient demographics, systemic treatment, and survival were
      examined. RESULTS: During the 3-year study period, 683 patients fitting the
      inclusion criteria were identified. First-line therapy was administered in 49.5%
      of patients; only 22.4% received further lines of therapy. The main reasons for
      withholding therapy were poor performance status [ps (43.2%)], rapidly
      deteriorating ps (31.9%), patient refusal of therapy (20.9%), and associated
      comorbidities (4%). Older age, the presence of brain metastasis at diagnosis, and
      non-small-cell histology were also associated with therapeutic restraint.
      Oncology referrals were infrequent in patients who did not receive therapy
      (32.2%). Older patients and those with a poor ps experienced superior survival
      when treatment was administered (hazard ratio: 0.25; 95% confidence interval:
      0.16 to 0.38; and hazard ratio: 0.44; 95% confidence interval: 0.23 to 0.87
      respectively; p < 0.001). CONCLUSIONS: Advanced lung cancer still poses a
      therapeutic challenge, with a high proportion of patients being deemed unfit for
      therapy. This issue cannot be resolved until appropriate measures are taken to
      ensure the inclusion of older patients and those with a relatively poor ps in
      large clinical trials. Immunotherapy might be interesting in this setting, given
      that it appears to be more tolerable. Another consequential undertaking would be
      the deployment of strategies to reduce wait times during the diagnostic process
      for patients with a high index of suspicion for lung cancer.

PMID- 28490935
TI  - Characteristics predicting outcomes of allogeneic stem-cell transplantation in
      relapsed acute myelogenous leukemia.
AB  - BACKGROUND: Allogeneic hematopoietic stem-cell transplantation (ahsct) is
      associated with significant morbidity and mortality, but it can cure carefully
      selected patients with acute myeloid leukemia (aml) in second remission (cr2). In
      a cohort of patients with aml who underwent ahsct in cr2, we determined the pre
      transplant factors that predicted for overall survival (os), relapse, and non
      relapse mortality. We also sought to validate the prognostic risk groups derived
      by Michelis and colleagues in this independent population. METHODS: In a
      retrospective chart review, we obtained data for 55 consecutive patients who
      underwent ahsct for aml in cr2. Hazard ratios were used to describe the
      independent effects of pre-transplant variables on outcome, and Kaplan-Meier
      curves were used to assess outcomes in the three prognostic groups identified by
      Michelis and colleagues. RESULTS: At 1, 3, and 5 years post-transplant, os was
      60%, 45.5%, and 37.5% respectively. Statistically significant differences in os,
      relapse mortality, and non-relapse mortality were not identified between the
      prognostic risk groups identified by Michelis and colleagues. Women were less
      likely than men to relapse, and a modified European Society for Blood and Marrow
      Transplantation (mebmt) score of 3 or less was associated with a lower non
      relapse mortality. CONCLUSIONS: The 37.5% 5-year os in this cohort suggests that,
      compared with other options, ahsct offers patients with aml in cr2 a better
      chance of cure. Our study supports the use of the mebmt score to predict non
      relapse mortality in this population.

PMID- 28490936
TI  - Rising rates of colorectal cancer among younger Iranians: is diet to blame?
AB  - BACKGROUND: Colorectal cancer (crc) is one of the most prevalent cancers in the
      world. Although the incidence of crc is currently very low in the older Iranian
      population compared with Western populations, young Iranians show a rising trend
      of crc-that is, the age-adjusted rate is close in the young Iranian population
      compared with the U.S. population, and the rate in older Iranians is much lower.
      METHODS: To assess a putative relationship between diet and a rising rate of crc
      in younger Iranians, a combined text word and mesh heading search strategy
      identified relevant studies through Google Scholar and medline. RESULTS: A
      critical look at diet among Iranians shows major issues that might be raising the
      risk for crc. There are also scenarios other than diet for the rise, such as the
      young age structure of the country. However, the actual scenario is more complex.
      CONCLUSIONS: In Iran, crc is one of the most common incident cancers and a common
      cause of cancer death. Primary and secondary prevention-with attention to a
      healthy lifestyle, physical activity, and screening-should be enhanced in the
      general population.

PMID- 28490937
TI  - Uptake of a 21-gene expression assay in breast cancer practice: views of academic
      and community-based oncologists.
AB  - PURPOSE: Advances in personalized medicine have produced novel tests and
      treatment options for women with breast cancer. Relatively little is known about
      the process by which such tests are adopted into oncology practice. The
      objectives of the present study were to understand the experiences of medical
      oncologists with multigene expression profile (gep) tests, including their
      adoption into practice in early-stage breast cancer, and the perceptions of the
      oncologists about the influence of test results on treatment decision-making.
      METHODS: We conducted a qualitative descriptive study involving interviews with
      medical oncologists from academic and community cancer centres or hospitals in 8
      communities in Ontario. A 21-gene breast cancer assay was used as the example of
      gep testing. Qualitative analytic techniques were used to identify the main
      themes. RESULTS: Of 28 oncologists who were approached, 21 (75%) participated in
      the study [median age: 43 years; 12 women (57%)]. Awareness and knowledge of gep
      testing were derived from several sources: international scientific meetings,
      participation in clinical studies, discussions with respected colleagues, and
      manufacturer-sponsored meetings. Oncologists observed that incorporating gep
      testing into their clinical practice resulted in several changes, including
      longer consultation times, second visits, and taking steps to minimize treatment
      delays. Oncologists expressed divergent opinions about the strength of evidence
      and added value of gep testing in guiding treatment decisions. CONCLUSIONS:
      Incorporation of gep testing into clinical practice in early-stage breast cancer
      required oncologists to make changes to their usual routines. The opinions of
      oncologists about the quality of evidence underpinning the test affected how much
      weight they gave to test results in treatment decision-making.

PMID- 28490938
TI  - Comparative survival in patients with brain metastases from non-small-cell lung
      cancer treated before and after implementation of radiosurgery.
AB  - INTRODUCTION: Survival after a diagnosis of brain metastasis in non-small-cell
      lung cancer (nsclc) is generally poor. We previously reported a median survival
      of approximately 4 months in a cohort of patients treated with whole-brain
      radiotherapy (wbrt). Since that time, we implemented a program of stereotactic
      radiosurgery (srs). In the present study, we examined survival and prognostic
      factors in a consecutive cohort of patients after the introduction of the srs
      program. METHODS: Data from a retrospective review of 167 nsclc patients with
      brain metastasis referred to a tertiary cancer centre during 2010-2012 were
      compared with data from a prior cohort of 91 patients treated during 2005-2007
      ("pre-srs cohort"). RESULTS: Median overall survival from the date of diagnosis
      of brain metastasis (4.3 months in the srs cohort vs. 3.9 months in the pre-srs
      cohort, p = 0.74) was not significantly different in the cohorts. The result was
      similar when the no-treatment group was excluded from the srs cohort. Within the
      srs cohort only, significant differences is overall survival were observed
      between treatment groups (srs, wbrt plus srs, wbrt, and no treatment), with
      improved survival being observed on univariate and multivariate analysis for
      patients receiving srs compared with patients receiving wbrt alone (p < 0.001).
      CONCLUSIONS: No improvement in survival was observed for nsclc patients with
      brain metastases after the implementation of srs. Selected patients (younger age,
      female sex, good performance status, fewer brain metastases) treated with srs
      appeared to demonstrate improved survival. However, those observations might also
      reflect better patient selection for srs or a greater tendency to offer those
      patients systemic therapy in addition to srs.

PMID- 28490939
TI  - Measuring quality care in localized renal cell cancer: use of appropriate
      preoperative investigations in a population-based cohort.
AB  - INTRODUCTION: Obtaining appropriate preoperative risk-specific staging
      investigations for localized renal cell carcinoma (rcc) is a recognized quality
      indicator. The goal of the present work was to determine the use and
      appropriateness of preoperative investigations in patients undergoing curative
      surgery for rcc. METHODS: This population-based retrospective study of patients
      having surgery for localized rcc recorded the use of preoperative imaging and
      laboratory investigations within 6 months of surgery. "Appropriate" stage
      specific investigations were determined using recognized published guidelines.
      RESULTS: The study cohort consisted of 544 patients with 72.8% being stage i,
      18.4% being stage ii, and 8.8% being stage iii by clinical TNM (2002) criteria.
      In 61.6%, chest imaging was obtained by chest radiography or computed tomography
      (ct) within 3 months preoperatively; in 75.6%, such imaging was obtained within 6
      months. Abdominal ct imaging was obtained in 97.1% of patients before surgery,
      with 77.5% of patients receiving such imaging within 3 months of surgery.
      Complete blood count, electrolytes, and creatinine were measured in 99.1% of
      patients, but those tests plus other recommended blood tests including calcium,
      alkaline phosphatase, and liver function were measured in only 17.7%.
      CONCLUSIONS: In this study, most patients received appropriate abdominal imaging,
      but chest imaging was underutilized in the overall cohort. Despite being
      recommended, blood tests such as liver function, alkaline phosphatase, and
      calcium were completed in fewer than 2 of 10 patients. This analysis provides the
      groundwork for quality improvement initiatives directed to the use of
      preoperative investigations in localized rcc.

PMID- 28490940
TI  - Systemic therapy in the curative treatment of head-and-neck squamous cell cancer:
      Cancer Care Ontario clinical practice guideline.
AB  - OBJECTIVE: The aim of the present work was to make recommendations about the use
      of systemically administered drugs in combination or in sequence with radiation
      (rt) or surgery, or both, for cure or organ preservation, or both, in patients
      with locally advanced nonmetastatic (stages iii-ivb) squamous cell carcinoma of
      the head and neck (lascchn). METHODS: The Meta-analysis of Chemotherapy in Head
      and Neck Cancer (mach-nc) reports have, de facto, guided practice since 2000, and
      so we searched the literature for systematic reviews published from January 2000
      to February 2015 in reference to five research questions. A search was also
      conducted up to February 2015 for randomized trials (rcts) not included in the
      meta-analyses. Recommendations were constructed using the Cancer Care Ontario
      Program in Evidence-Based Care practice guidelines development cycle. RESULTS: In
      addition to updated mach-nc reports, five additional meta-analyses and thirty
      rcts were identified. Five recommendations for lascchn treatment were generated
      based on those data. Concurrent chemoradiation (ccrt) is recommended to maximize
      the chance of cure in patients less than 71 years of age when rt is used as
      definitive treatment. The same recommendation also applies to patients with
      resected lascchn considered to be at high risk for locoregional recurrence. For
      lascchn patients who are candidates for organ preservation strategies and would
      otherwise require total laryngectomy, either ccrt or induction chemotherapy,
      followed by rt or surgery based on tumour response is recommended. The addition
      of cetuximab to intensified rt (concomitant boost or hyperfractionated schedule)
      is an alternative to ccrt. Routine use of induction chemotherapy to improve
      overall survival is not recommended. CONCLUSIONS: We were able to use high-level
      evidence from patients receiving rt as definitive or postoperative treatment to
      generate recommendations for the use of systemic therapy in the treatment of
      lascchn. A limitation is a lack of stratification for human papillomavirus
      related cancers of the oropharynx. One rct provided evidence for the use of
      cetuximab as an alternative to chemotherapy in the definitive rt setting.
      Concurrent chemoradiation provides one strategy for larynx preservation, but the
      best strategy is unclear. Use of induction chemotherapy does not improve overall
      survival, and its use should be limited to patients requiring immediate tumour
      downsizing before local therapy.

PMID- 28490941
TI  - Effectiveness of Hypnosis in Combination with Conventional Techniques of Behavior
      Management in Anxiety/Pain Reduction during Dental Anesthetic Infiltration.
AB  - Background and Objective. Anxiety/pain are experiences that make dental treatment
      difficult for children, especially during the time of anesthesia. Hypnosis is
      used in pediatric clinical situations to modify thinking, behavior, and
      perception as well as, recently, in dentistry; therefore the aim of this study
      was to evaluate the effectiveness of hypnosis combined with conventional behavior
      management techniques during infiltration anesthetic. Methods. Anxiety/pain were
      assessed with the FLACC scale during the anesthetic moment, as well as heart rate
      variability and skin conductance before and during the anesthetic moment, between
      the control and experimental group. Results. A marginal statistical difference (p
      = 0.05) was found in the heart rate between baseline and anesthetic moment, being
      lower in the hypnosis group. No statistically significant differences were found
      with the FLACC scale or in the skin conductance (p > 0.05). Conclusion. Hypnosis
      combined with conventional behavior management techniques decreases heart rate
      during anesthetic infiltration showing that there may be an improvement in
      anxiety/pain control through hypnotic therapy.

PMID- 28490943
TI  - Comparing the performance of granular coral limestone and Leca in adsorbing Acid
      Cyanine 5R from aqueous solution.
AB  - The effect of granular coral limestone and Leca as adsorbents for removing Acid
      Cyanine 5R (AC5R) from aqueous solution was studied. The optimum pH and adsorbent
      particles size in both adsorbents were determined to be 3 and 297 MUm,
      respectively. The optimum dosages of coral limestone and granular Leca were 0.150
      and 0.145 g/mg of dye, respectively. Also, results have shown that the adsorption
      efficiency by both coral limestone and Leca increased with the decreasing
      adsorbent particles size. Moreover, under similar conditions, the maximum removal
      efficiency by granular coral limestone and Leca was 94% and 88%, respectively.
      The results revealed that the performance of granular coral limestone was better
      in AC5R removal than that of Leca granulated under such condition. In total,
      granular coral limestone and Leca act as suitable adsorbents for removing dye
      pollutants from an aqueous solution.

PMID- 28490942
TI  - Comparison of Incidences of Intravascular Injection between Medial and Lateral
      Side Approaches during Traditional S1 Transforaminal Epidural Steroid Injection.
AB  - Purpose. Intravascular injection rates are higher during traditional S1
      transforaminal epidural steroid injection (TFESI) compared with lumbar
      transforaminal injection. We compared the incidences of intravascular injection
      between the medial and lateral approaches to the S1 foramen during S1 TFESI.
      Materials and Methods. A total of 139 patients underwent one or more TFESIs (170
      total injections). The patients received S1 TFESI by either medial or lateral
      side of S1 foramen under fluoroscopic anteroposterior view using digital
      subtraction method. The intravascular injection rates, epidural spread patterns,
      and contrast volumes required to reach the superior aspect of the L5-S1
      intervertebral disc (SIVD) were compared between groups. Results. Intravascular
      injection rates during S1 TFESI were significantly lower in the medial approach
      compared with the lateral approach patients (4.9% versus 38.6%, resp., P <
      0.001). The medial approach group had more epidural spread to the L5-S1 SIVD than
      the lateral group (82.1% versus 58.8%, resp.); lower contrast volume amounts were
      required to extend the L5-S1 SIVD (1.46 +/- 0.48 versus 1.90 +/- 0.62, resp.).
      Conclusion. During S1 TFESI, approaching the needle towards the medial part of
      the S1 foramen may reduce intravascular injection risk.

PMID- 28490944
TI  - Phytochemical evaluation of roots of Plumbago zeylanica L. and assessment of its
      potential as a nephroprotective agent.
AB  - Search for medicinal plants to treat kidney disorders is an important topic on
      phytotherapeutical research. Plumbago zeylanica L. is an important medicinal
      plant with hepatoprotective, anti-inflammatory, anti-diabetic, anti-cancer and
      anti-hyperlipidemic activities. In the present study, the protective effect of
      hydroalcoholic extract of P. zeylanica (HAPZ) in cisplatin induced nephrotoxicity
      was analyzed in Swiss albino mice. Treatment with higher dose (400 mg/kg) of HAPZ
      significantly reversed the adverse effect of cisplatin on kidney weight, serum
      urea and creatinine, indicating their renoprotective effect. The antioxidant
      effect of the drug is evident from its significant effect on Catalase,
      Glutathione peroxidase and lipid peroxidation activities.

PMID- 28490945
TI  - Sanitary impact evaluation of drinking water in storage reservoirs in Moroccan
      rural area.
AB  - In Morocco, storage reservoirs are particular systems of water supply in rural
      areas. These reservoirs are fed with rainwater and/or directly from the river,
      which are very contaminated by several pathogenic bacteria. They are used without
      any treatment as a drinking water by the surrounding population. In this context,
      the aim of this study is to evaluate the impact of consuming contaminated water
      stored in reservoirs on health status for six rural communities located in Assif
      El Mal, Southern East of Marrakech. This was investigated using a classical
      methodology based on population survey and by molecular approach using PCR-DGGE
      technique to determine the intestinal bacterial diversity of consumers. The
      survey showed that, the residents of the studied area suffered from numerous
      health problems (diarrheal diseases, vomiting or hepatitis A) due to the lack of
      waste management infrastructures. The consumer's stool analysis by molecular
      approach revealed that numbers of Escherichia coli, Aeromonas hydrophila and
      Clostridia, were significantly higher in the diarrheal feces. In addition, PCR
      DGGE study of the prevalence and distribution of bacteria causing human diseases,
      confirmed that, there is a relationship between water bacterial contaminations of
      storage reservoirs and microbial disease related health status. Therefore, water
      reservoir consumption is assumed to be the mean way of exposure for this
      population. It's clear that this approach gives a very helpful tool to confirm
      without any doubt the relationship between water bacterial contamination and
      health status.

PMID- 28490946
TI  - Plant species and communities assessment in interaction with edaphic and
      topographic factors; an ecological study of the mount Eelum District Swat,
      Pakistan.
AB  - The current analyses of vegetation were aimed to study the different effects of
      environmental variables and plant species and communities interaction to these
      variables, identified threats to local vegetation and suggestion for remedial
      measures in the Mount Eelum, Swat, Pakistan. For assessment of environmental
      variability quantitative ecological techniques were used through quadrats having
      sizes of 2 * 2, 5 * 5 and 10 * 10 m2 for herbs, shrubs and trees respectively.
      Result of the present study revealed 124 plant species in the study area.
      Canonical Correspondence Analysis (CCA) was used to analyze the ecological
      gradient of vegetation. The environmental data and species abundance were used in
      CANOCO software version 4.5. The presence absence data of plant species were
      elaborated with Cluster and Two Way Cluster Analysis techniques using PC-ORD
      version 5 to show different species composition that resulted in five plant
      communities. Findings indicate that elevation, aspect and soil texture are the
      strongest variables that have significant effect on species composition and
      distribution of various communities shown with P value 0.0500. It is recommended
      to protect and use sensibly whole of the Flora normally and rare species
      particularly in the region.

PMID- 28490948
TI  - Preparation and quality evaluation of coenzyme Q10 long-circulating liposomes.
AB  - The aim of this work was to prepare coenzyme Q10 (CoQ10) long-circulating
      liposomes, and establish the quality standard to determine the content and
      entrapment efficiency. CoQ10 long-circulating liposomes were prepared by the film
      dispersion method, HPLC assay for the determination of CoQ10 was developed. Free
      drugs and liposomes were separated using the protamine aggregation method and
      entrapment efficiency was determined. The liposomes were homogeneous and the mean
      diameter was 166.0 nm, Zeta potential was -22.2 mV. The content and entrapment
      efficiency of CoQ10 were 98.2% and 93.2% for three batches of liposomes,
      respectively. The lyophilized form of liposomes prepared by freeze-drying showed
      stable quality characteristics during storage. The formulation and preparative
      method can be used to prepare CoQ10 long-circulating liposomes with high
      entrapment efficiency and high quality, the determination method of drug content
      and entrapment efficiency were effective and rapid and can be used for quality
      evaluation of liposomes.

PMID- 28490947
TI  - Preliminary fabrication and characterization of electron beam melted Ti-6Al-4V
      customized dental implant.
AB  - The current study was aimed to fabricate customized root form dental implant
      using additive manufacturing technique for the replacement of missing teeth. The
      root form dental implant was designed using GeomagicTM and MagicsTM, the designed
      implant was directly manufactured by layering technique using ARCAM A2TM electron
      beam melting system by employing medical grade Ti-6Al-4V alloy powder.
      Furthermore, the fabricated implant was characterized in terms of certain
      clinically important parameters such as surface microstructure, surface
      topography, chemical purity and internal porosity. Results confirmed that,
      fabrication of customized dental implants using additive rapid manufacturing
      technology offers an attractive method to produce extremely pure form of
      customized titanium dental implants, the rough and porous surface texture
      obtained is expected to provide better initial implant stabilization and superior
      osseointegration.

PMID- 28490949
TI  - Function of PD-L1 in antitumor immunity of glioma cells.
AB  - Human glioma is a highly fatal tumor with a significant feature of immune
      suppression. The functions of PD-L1 refer to co-simulation and immune regulation.
      To investigate expression and functional activity of PD-L1 in human glioma cell
      in vivo and in vitro. Expressions of PD-L1mRNA and protein in the human glioma
      cell line were analyzed with quantitative RT-PCR and flow cytometer; and then
      expression of PD-L1 in tissue specimens of 10 glioma patients was treated with
      immunohistochemical analysis; glioma cell and allogeneic CD4+ and CD8+ T cells
      were co-cultured, and cytokine IFN-gamma, IL-2 and IL-10 in cultured supernatant
      fluid were determined with ELISA; upon blocking the interaction between glioma
      cell and the immune cell with PD-L1 monoclonal antibody (5H1), surface markers on
      immune cells were analyzed using flow cytometer. All human glioma cell lines
      constitutively expressed PD-L1, and IFN-gamma induced glioma cell to highly
      express PD-L1. It was shown through immunohistochemical analysis that glioma
      specimen expressed PD-L1, while expression of PD-L1 was not observed in normal
      tissue and normal human brain near the tumor location. The release of IFN-gamma
      and IL-2 was inhibited, while IL-10 was increased slightly. Glioma cell may
      escape from immune recognition and injury with the help of PD-L1, which is a
      significant pathogenic mechanism of glioma.

PMID- 28490950
TI  - Self-medication and antibiotic resistance: Crisis, current challenges, and
      prevention.
AB  - The present study aims to explore the crisis of antibiotic resistance and
      discover more about the current challenges related to self-medication. The
      current challenges related to antibiotic resistance are unique and differ from
      the challenges of the past since new bacterial pathogens are involved and
      continue to evolve. Strains with resistance to multiple antibiotic classes have
      emerged which the discovery of new antibiotics has failed to match. The
      consequences of antibiotic resistance are grave with mortality and morbidity
      continually on the rise. This paper also highlights the possible interventions
      that can be effective at the micro or individual level in the prevention of
      development of antibiotic resistance.

PMID- 28490951
TI  - Gene introgression from common wheat into Aegilops L.
AB  - Group of experiments were carried out to verify possibility of gene introgression
      from common wheat into Aegilops. The artificial indoor crossbreed was conducted
      using 7 genotypes from 4 wheat relative species as female, and common wheat as
      male. The experiment result shows that different species has variable cross
      ability. Among the 4 Aegilops species, the highest cross rate is from the
      combination of Aegilops tauschii * Triticum aestivum (46.49% for genotype Ae42,
      22.58% for Y92), the second is from Aegilops ovata * T. aestivum (14.76% for
      Y100, 12.11% for Ae23), the third is from Aegilops cylindrica * T. aestivum
      (2.23% for Ae7, 8.50% for Y145), and the lowest is from Aegilops speltoides * T.
      aestivum (0.19%). Hybrid embryos from different combinations have different
      ability of callus initiation and germination. The hybrid embryos from A. ovata/T.
      aestivum and Ae. tauschii/T. aestivum have a higher level of callus initiation
      and germination. Ae. cylindrica/T. aestivum has a middle level, while the Ae.
      speltoides has a lower level. The interspecific hybrids between Aegilops and
      common wheat have so low fertility. In back-crosses, the seed-set rate of hybrids
      of Ae. ovata/T. aestivum is 3.71% and 4.36% respectively back-crossed with male
      and female parents, while for hybrids of Ae. cylindrica/T. aestivum, they were 0
      and 0.33% respectively, and for Ae. tauschii/T. aestivum, 0.33% and 0
      respectively. On selfing of the hybrids, the seed-set rate is 0 (no seed set from
      9750 florets) for the combination of Ae. cylindrica/T. aestivum, 0.044% (3 selfed
      seeds out of 6870 florets) for Ae. ovata/T. aestivum and 0 (no seed set from 7253
      florets) for Ae. tauschii/T. aestivum. The research suggests that the probability
      of gene introgression from T. aestivum into Aegilops species is very low in
      nature.

PMID- 28490952
TI  - Biological activity of Xanthium strumarium seed extracts on different cancer cell
      lines and Aedes caspius, Culex pipiens (Diptera: Culicidae).
AB  - Effects of methanol extracts of Xanthium strumarium on different cancer cell
      lines and on the mortality rates of Aedes caspius, Culex pipiens (Diptera:
      Culicidae) were investigated. Among the cell lines tested, the Jurkat cell line
      was the most sensitive to the methanol extract and ethyl acetate fraction, with
      reported LC50 values of 50.18 and 48.73 MUg/ml respectively. Conversely, methanol
      extracts were not that toxic to the A549 cell line though the toxicity increased
      on further purification. The percentage of growth inhibition was dose dependent
      for the methanol extract and ethyl acetate fraction. The ethyl acetate fraction
      showed higher toxicity to all cell lines tested when compared to the methanol
      extract. The results showed that methanol extracts of plant seeds caused 100%
      mortality of mosquito larvae at a concentration of 1000 MUg/ml after 24 h of
      treatment. The LC50 and LC90 values of X. strumarium were found to be 531.07 and
      905.95 MUg/ml against Ae. caspius and 502.32 and 867.63 MUg/ml against Cx.
      Pipiens, respectively. From the investigations, it was concluded that the crude
      extract of X. strumarium showed a weak potential for controlling the larval
      instars of Ae. caspius and Cx. pipiens. However, on further purification the
      extract lost the larvicidal activity. The ethyl acetate fraction showed higher
      toxicity to all cell lines tested when compared to the methanol extract. The
      ethyl acetate fraction investigated in this study appears to have a weak
      larvicidal activity but a promising cytotoxic activity. Future studies will
      include purification and investigation in further detail of the action of X.
      strumarium on Cancer Cell Lines and mosquitoes.

PMID- 28490953
TI  - Determination of seed viability of eight wild Saudi Arabian species by
      germination and X-ray tests.
AB  - Our purpose was to evaluate the usefulness of the germination vs. the X-ray test
      in determining the initial viability of seeds of eight wild species (Salvia
      spinosa, Salvia aegyptiaca, Ochradenus baccatus, Ochradenus arabicus, Suaeda
      aegyptiaca, Suaeda vermiculata, Prosopisfarcta and Panicumturgidum) from Saudi
      Arabia. Several days were required to determine viability of all eight species
      via germination tests, while immediate results on filled/viable seeds were
      obtained with the X-ray test. Seeds of all the species, except Sa.aegyptiaca,
      showed high viability in both the germination (98-70% at 25/15  degrees C, 93-66%
      at 35/25  degrees C) and X-ray (100-75%) test. Furthermore, there was general
      agreement between the germination (10% at 25/15  degrees C and 8% at 35/25 
      degrees C) and X-ray (5%) tests that seed viability of Sa.aegyptiaca was very
      low, and X-ray analysis revealed that this was due to poor embryo development.
      Seeds of P.farcta have physical dormancy, which was broken by scarification in
      concentrated sulfuric acid (10 min), and they exhibited high viability in both
      the germination (98% at 25/15  degrees C and 93% at 35/25  degrees C) and X-ray
      (98%) test. Most of the nongerminated seeds of the eight species except those of
      Sa.aegyptiaca were alive as judged by the tetrazolium test (TZ). Thus, for the
      eight species examined, the X-ray test was a good and rapid predictor of seed
      viability.

PMID- 28490954
TI  - Pretarsus structure in relation to climbing ability in the ants Brachyponera
      sennaarensis and Daceton armigerum.
AB  - We studied the external and internal pretarsus structure of the ants Brachyponera
      sennaarensis and Daceton armigerum in relation to their very different climbing
      ability. B. sennaarensis is a ground-dwelling species that is not able to climb
      vertical smooth walls. They have a pair of straight pretarsal claws with an
      average claw tip angle of 56 degrees, while the ventral tarsal surface lacks fine
      hairs that touch the substrate. They have no adhesive pad on the vestigial
      arolium, while the arolium gland is very small. D. armigerum, on the other hand,
      is an arboreal and thus well-climbing species with a very strong grip on the
      substrate. Their pretarsal claws are very hooked, with a claw tip angle around 75
      degrees. They have dense arrays of fine hairs on the ventral tarsal surface, a
      well-developed arolium and arolium gland. These clearly different morphological
      characteristics are in line with the opposite climbing performance of both
      species.

PMID- 28490955
TI  - Protection of oxidative stress induced apoptosis in osteosarcoma cells by
      dihydromyricetin through down-regulation of caspase activation and up-regulation
      of BcL-2.
AB  - Current study was aimed to investigate the effect of dihydromyricetin on hydrogen
      peroxide induced oxidative stress in the osteosarcoma cells. MTT assay showed
      that hydrogen peroxide treatment at a concentration of 100 MUM caused a
      significant (p < 0.005) reduction in the viability of MG63 cells. However,
      reduction in cell viability caused by 100 MUM concentration of hydrogen peroxide
      was completely prevented on incubation with 30 MUM dose of dihydromyricetin.
      Treatment with 100 MUM concentration of hydrogen peroxide for 24 h led to
      condensation of chromatin material, rounding of cell shape and detachment of
      cells. The results from flow cytometry using annexin V-FITC and PI double
      staining showed apoptosis induction in 47.84 +/- 5.21% cells on treatment with
      100 MUM concentration of hydrogen peroxide compared to 2.32 +/- 0.54% in
      controlcells. The apoptotic alterations in MG63 cell morphology were prevented
      significantly on pre-treatment with 30 MUM doses of dihydromyricetin for 48 h.
      Annexin V-FITC and PI staining showed reduction of hydrogen peroxide induced
      apoptotic cell percentage to 3.07 +/- 0.86% on pre-treatment of MG63 cells with
      30 MUM dose of dihydromyricetin. Western blot analysis showed a significant
      increase in the activation of caspase-3 and -9 on treatment of MG63 cells for 24
      h with 100 MUM concentration of hydrogen peroxide. The expression level of Bcl-2
      was decreased significantly by 100 MUM concentration of hydrogen peroxide in MG63
      cells. However, pre-treatment of MG63 cells with 30 MUM dose of dihydromyricetin
      for 48 h significantly prevented hydrogen peroxide induced increase in caspase-3
      and -9 levels and reduction in Bcl-2 level. Thus dihydromyricetin prevents
      hydrogen peroxide induced reduction in viability and induction of apoptosis in
      MG63 cells through down-regulation of caspase activation and up-regulation of Bcl
      2 levels.

PMID- 28490956
TI  - Changes in the NFkappaB and E-cadherin expression are associated to diabetic
      nephropathy inPsammomys obesus.
AB  - Diabetes mellitus is a major leading cause of end-stage renal failure,
      characterized by kidney inflammation and glomerular dysfunction, in worldwide.
      Kidney inflammation is associated to modifications in the expression levels of
      pro-inflammatory molecules, such as nuclear factor-kappaB (NFkappaB) and adhesion
      molecules, such as E-cadherin, leading to glomerular dysfunction. However, the
      relationships between these two processes in human diabetic nephropathy remain an
      open question. Since Psammomys obesus is an ideal animal model to study diabetes
      mellitus temporal evolution, we have used this model to study the correlation
      between kidney structural changes and modification on the expression levels of
      NFkappaB and E-cadherin over time. We have demonstrated that, after induction of
      diabetes metillus with a high energy diet (HED), P. obesus develops the
      characteristic symptoms of human disease. In detail, at the third month nuclear
      factor NFkappaB is expressed in the kidney of diabetic P. obesus and structural
      renal changes, such as mesangial expansion or interstitial fibrosis, are
      detectable; at 6 months, thickening of glomerular basement membrane, glomerular
      sclerosis, and tubular atrophy occurs; at 9 months, symptoms of the final stages
      of the disease, such as down expression of E-cadherin, happens. As a result of
      these observations we proposed that NFkappaB activation and E-cadherin down
      expression are interlinked on diabetic kidney disease (DKD).

PMID- 28490957
TI  - Isolation of the symbiotic fungus of Acromyrmex pubescens and phylogeny of
      Leucoagaricus gongylophorus from leaf-cutting ants.
AB  - Leaf-cutting ants live in an obligate symbiosis with a Leucoagaricus species, a
      basidiomycete that serves as a food source to the larvae and queen. The aim of
      this work was to isolate, identify and complete the phylogenetic study of
      Leucoagaricus gongylophorus species of Acromyrmex pubescens. Macroscopic and
      microscopic features were used to identify the fungal symbiont of the ants. The
      ITS1-5.8S-ITS2 region was used as molecular marker for the molecular
      identification and to evaluate the phylogeny within the Leucoagaricus genus. One
      fungal symbiont associated with A. pubescens was isolated and identified as L.
      gongylophorus. The phylogeny of Leucoagaricus obtained using the ITS molecular
      marker revealed three well established monophyletic groups. It was possible to
      recognize one clade of Leucoagaricus associated with phylogenetically derived
      leaf-cutting ants (Acromyrmex and Atta). A second clade of free living forms of
      Leucoagaricus (non-cultivated), and a third clade of Leucoagaricus associated
      with phylogenetically basal genera of ants were also recognized. The clades
      corresponded to traditional taxonomic groups, and were differentiated by
      ecological habitats of different species.

PMID- 28490958
TI  - Transplantation of human neonatal foreskin stromal cells in ex vivo organotypic
      cultures of embryonic chick femurs.
AB  - We have previously reported that human neonatal foreskin stromal cells (hNSSCs)
      promote angiogenesis in vitro and in chick embryo chorioallantoic membrane (CAM)
      assay in vivo. To examine the in vivo relevance of this observation, we examined
      in the present study the differentiation potential of hNSSCs in ex vivo
      organotypic cultures of embryonic chick femurs. Isolated embryonic chick femurs
      (E10 and E11) were cultured for 10 days together with micro-mass cell pellets of
      hNSSCs, human umbilical vein endothelial cells (HUVEC) or a combination of the
      two cell types. Changes in femurs gross morphology and integration of the cells
      within the femurs were investigated using standard histology and
      immunohistochemistry. After 10 days, the femurs that were cultured in the
      presence of hNSSCs alone or hNSSC + HUVEC cells grew longer, exhibited thicker
      diaphysis and an enlarged epiphyseal region compared to control femurs cultured
      in the absence of cells. Analysis of cell-femur interactions, revealed intense
      staining for CD31 and enhanced deposition of collagen rich matrix along the
      periosteum in femurs cultured with hNSSCs alone or hNSSCs + HUVEC and the most
      pronounced effects were observed in hNSSC + HUVEC cultures. Our data suggest that
      organotypic cultures can be employed to test the differentiation potential of
      stem cells and demonstrate the importance of stem cell interaction with 3D-intact
      tissue microenvironment for their differentiation.

PMID- 28490959
TI  - Physiological parameters correlated with Tomato Mosaic Virus inducing defensive
      response in Datura metel.
AB  - Programed cell death resembles a real nature active defense in Datura metel
      against TMV after three days of virus infection. This adaptive plant immune
      response was quantitatively assessed against Tomato Mosaic Virus infection by the
      following physiological markers; Chlorophyll-a (mg/g), Chlorophyll-b (mg/g),
      total protein (mg/g), hydrogen peroxide H2O2 (MUmol/100 mg), DNA (MUg/100 mg),
      RNA (MUg/100 mg), Salicylic acid (MUg/g), and Comet Assays. Parameters were
      assessed for asymptomatic healthy and symptomatic infected detached leaves. The
      results indicated H2O2 and Chlorophyll-a as the most potential parameters.
      Chlorophyll-a was considered the only significant predictor variant for the H2O2
      dependent variant with a P value of 0.001 and R-square of 0.900. The plant immune
      response was measured within three days of virus infection using the cutoff value
      of H2O2 (?1.095 MUmol/100 mg) and (?3.201 units) for the tail moment in the Comet
      Assay. Their percentage changes were 255.12% and 522.40% respectively which
      reflects the stress of virus infection in the plant. Moreover, H2O2 showed 100%
      specificity and sensitivity in the symptomatic infected group using the receiver
      operating characteristic (ROC). All tested parameters in the symptomatic infected
      group had significant correlations with twenty-five positive and thirty-one
      negative correlations where the P value was <0.05 and 0.01. Chlorophyll-a
      parameter had a crucial role of highly significant correlation between total
      protein and salicylic acid. Contrarily, this correlation with tail moment unit
      was (r = -0.930, P < 0.01) where the P value was <0.01. The strongest significant
      negative correlation was between Chlorophyll-a and H2O2 at P < 0.01, while
      moderate negative significant correlation was seen for Chlorophyll-b where the P
      value < 0.05. The present study discloses the secret of the three days of rapid
      transient production of activated oxygen species (AOS) that was enough for having
      potential quantitative physiological parameters for defensive plant response
      toward the virus.

PMID- 28490960
TI  - Chemical composition, antibacterial and antifungal activities of flowerhead and
      root essential oils of Santolina chamaecyparissus L., growing wild in Tunisia.
AB  - The antimicrobial properties of essential oil from various Santolina species have
      not been investigated enough in the previous studies dealing with the biological
      activities of medicinal plants. In Tunisia, Santolina chamaecyparissus L.
      (Asteraceae) is the only Santolina species recorded and is used as vermifuge and
      emmenagogue. The chemical composition, antibacterial and antifungal properties of
      essential oils from the flowerheads and roots of spontaneous S. chamaecyparissus
      growing in Tunisia and the chemical composition which leads to the Tunisian
      chemotype are investigated here for the first time. Essential oils isolated by
      hydro distillation from flowerheads and roots of S. chamaecyparissus were
      analyzed by GC and GC/MS. Two methods served for antimicrobial assays of the
      essential oils: diffusion in a solid medium and micro-well dilution assay.
      Antifungal tests were carried out by the agar incorporation method. Sixty-seven
      constituents were identified from the essential oil of the flowerhead. The major
      constituents were: 1,8-cineole and beta-eudesmol. Two non identified compounds
      were present at the highest concentration in root oil. Flowerhead oil was
      characterized by high contents in monoterpenes and sesquiterpenes oxygenated
      compounds. The flowerhead essential oil demonstrated potent of antibacterial
      properties against Pseudomonas aeruginosa ATCC and Enterococcus faecalis ATCC,
      with MIC of 0.625 MUg/ml. These findings demonstrate that the flowerhead
      essential oils of S. chamaecyparissus have excellent antibacterial properties and
      for this reason they could contribute to decrease the problem of microbial
      resistance to antibiotics.

PMID- 28490961
TI  - Radiofrequency radiations induced genotoxic and carcinogenic effects on chickpea
      (Cicer arietinum L.) root tip cells.
AB  - Present study was under taken to predict the possible DNA damages (genotoxicity)
      and carcinogenicity caused by radiofrequency radiations (RF) to living tissue.
      Dry seeds of chickpea were treated with GSM cell phone (900 MHz) and laptop (3.31
      GHz) as RF source for 24 and 48 h. Untreated seeds were used as (0 h) negative
      control and Gamma rays (250 Gray) as positive control. Plant chromosomal
      aberration assay was used as genotoxicity marker. All the treatment of RF
      inhibits seed germination percentage. 48 h laptop treatment has the most negative
      effect as compared to untreated control. A decrease was observed in mitotic index
      (M.I) and increase in abnormality index (A.I) with the increase in exposure
      duration and frequency in (Hz). Cell membrane damages were also observed only in
      48 h exposure of cell phone and laptop (RF). Maximum nuclear membrane damages and
      ghost cells were again recorded in 48 h exposure of cell phone and laptop. The
      radiofrequency radiations (900 MHz and 3.31 GHz) are only genotoxic as they
      induce micronuclei, bi-nuclei, multi-nuclei and scattered nuclei but could be
      carcinogenic as 48 h incubation of RF induced fragmentation and ghost cells.
      Therefore cell phones and laptop should not be used unnecessarily to avoid
      possible genotoxic and carcinogenic effects.

PMID- 28490962
TI  - Effects of perinatal exposure to Zamzam water on the teratological studies of the
      mice offspring.
AB  - Zamzam water is well documented for plenty of medicinal value for curing illness.
      In the present study, the effects of perinatal consumption of Zamzam and normal
      drinking water by the pregnant mice on their offspring's physical parameters,
      early sensory motor reflexes, locomotor activities, acetylcholinesterase (AChE)
      activity in the homogenize brain tissue and blood parameters were compared. To
      achieve that; Zamzam water was given to female Swiss-Webster strain mice as the
      only source of drinking fluid and the control animals were administered plain tap
      water. Treatment started from the first day of pregnancy and continued until the
      postnatal day fifteen of delivery. All offspring were subjected to various tests.
      The rate of body weight gain remained relatively unaffected until the second week
      of weaning period, however; in the last week the offspring exposed to Zamzam
      water gained significant body weight as compared to their control offspring.
      Furthermore, the opening of eyes and appearance of body hairs in Zamzam exposed
      pups remained unaffected as compared to the controls. The sensory motor reflexes
      in Zamzam exposed pups after birth and during the first two weeks of weaning
      period were significantly increased. Locomotor Activity Test performed in the
      male and female offspring after weaning period showed a significant decrease in
      the male and increase in the female on most of the elements of this test due to
      Zamzam exposure. AChE activity in the homogenized brain tissue and blood
      parameters were unaffected as compared to the controls, the present Zamzam
      effects in the offspring are possibly via in utero action and/or via mother's
      milk.

PMID- 28490963
TI  - Analysis of the bacterial strains using Biolog plates in the contaminated soil
      from Riyadh community.
AB  - Routine manufacture, detonation and disposal of explosives in land and
      groundwater have resulted in complete pollution. Explosives are xenobiotic
      compounds, being toxic to biological systems, and their recalcitrance leads to
      persistence in the environment. The methods currently used for the remediation of
      explosive contaminated sites are expensive and can result in the formation of
      toxic products. The present study aimed to investigate the bacterial strains
      using the Biolog plates in the soil from the Riyadh community. The microbial
      strains were isolated using the spread plate technique and were identified using
      the Biolog method. In this study we have analyzed from bacterial families of soil
      samples, obtained from the different sites in 5 regions at Explosive Institute.
      Our results conclude that Biolog MicroPlates were developed for the rapid
      identification of bacterial isolates by sole-carbon source utilization and can be
      used for the identification of bacteria. Out of five communities, only four
      families of bacteria indicate that the microbial community lacks significant
      diversity in region one from the Riyadh community in Saudi Arabia. More studies
      are needed to be carried out in different regions to validate our results.

PMID- 28490964
TI  - Effect of long-term exposure of mice to 900 MHz GSM radiation on experimental
      cutaneous candidiasis.
AB  - Mobile phones communicate with base stations using 900 MHz microwaves. The
      current study was aimed to survey the effects of long-term 900 MHz microwave
      exposure of mice on experimentally induced cutaneous candidiasis. Forty inbred,
      male, BALB/c mice were randomly divided into four groups. Cutaneous lesions with
      Candida albicans were experimentally induced on the lateral-back skin of the 20
      mice. One group of the diseased mice were exposed (6 h per day and 7 d per week)
      to 900 MHz microwave radiation, while the other groups were not exposed. Two
      unexposed control groups were also included. The skin lesions were regularly
      monitored and the live candida cell density was enumerated using the colony
      forming unit (CFU) assay. The process was repeated after a one week resting
      interval. One week later, all mice were challenged through intra tail veins using
      LD90 dose of C. albicans. Mortality of the mice was recorded and the candida load
      of the kidney homogenates from died animals was counted. 900 MHz microwave
      exposed mice had 1.5 day and 3.7 day delays on wound healing in stages two. Live
      Candida inoculated Wave exposed (LCW) mice also showed higher yeast loads in skin
      lesions at days 5, 7 and 9 post inoculation. Survival analysis of live candida
      challenged mice showed the radiation exposed group is prone to death induced by
      systemic infection and candida enumeration from the kidney homogenates showed
      radiation exposed animals have had significantly higher yeast load in the tissue.
      In collection, long-term 900 MHz radiation exposure of mice led to longevity of
      skin wounds and susceptibility of the animals to systemic challenge and higher
      incidences of microorganisms in internal tissues.

PMID- 28490965
TI  - Protective effects of fennel oil extract against sodium valproate-induced
      hepatorenal damage in albino rats.
AB  - Foeniculum vulgare (Apiaceae) is commonly known as fennel. This herb is well
      known worldwide and traditionally used as curative herbal therapy for the
      treatment of epileptic disease, seizurescarminative, digestive, lactogogue,
      diuretic, treating respiratory and gastrointestinal disorders. The aim of present
      study is to investigate the possible effect of fennel oil against the toxicity of
      Sodium-Valproic (SVP) in albino rats. In order to assess the protection of fennel
      oil on SVP induced hepato- and nephro-toxicity, male albino rats were treated
      with 1 ml/kg b.w fennel oil 3 days/week for 6 weeks. The biochemical analyses of
      hepatic enzymes were evaluated by estimating blood biomarkers of liver and renal
      damage along with histological examination. The results obtained from this work
      showed that treating animals with SVP lead to many histopathological alterations
      in the liver and kidney tissues. The effect appeared in the liver tissue include
      leukocyte infiltrations, cytoplasmic vacuolization of the hepatocytes, fatty
      degeneration and congestion of blood vessels. This commonly used chemical (SVP)
      caused some unwanted effects on the kidney cortex which histologically observed
      as degeneration in renal tubules, atrophy of the glomeruli and edema. Biochemical
      results also revealed an abnormal increase in the enzyme level of AST, SAT, ALP,
      bilirubin, creatinine and urea-nitrogen, with a noticed decrease in total protein
      content. However, the results of treated rats with SVP plus fennel oil showed
      some positive histopathological changes in both the liver and kidney tissues.
      These results have confirmed that fennel oil has positive effects on the
      histological structure of the liver and kidney and the biochemical levels of AST,
      ALT, ALP, bilirubin, total proteins, creatinine and urea. It is concluded that
      fennel oil has various pharmacological properties including antioxidant, anti
      cancer activity, anti-inflammatory. These valuable effects might be due to the
      presence of aromatic compounds trans-anethole. This useful properties of fennel
      plant could be due to its antioxidant activity that prevents the toxicity of SVP.

PMID- 28490966
TI  - Survey of the reptilian fauna of the Kingdom of Saudi Arabia. VI. The snake fauna
      of Turaif region.
AB  - A collection of snakes in Turaif region, Kingdom of Saudi Arabia, an area that
      has been poorly documented for reptiles, consists of 28 specimens representing 11
      species belonging to 4 families (Colubridae, Elapidae, Viperidae and
      Atractaspididae). This study presents the first comprehensive inventory of the
      herpetofauna of the Turaif province of Saudi Arabia. Co-ordinates: Latitude,
      longitude and altitude, of the collected specimens were mapped using GPS. Three
      of the snake species Lytorhynchus diadema, Pseudocerastes fieldi and
      Walterinnesia morgani reported by the authors in the present survey proved to be
      new records for Turaif region of Saudi Arabia.

PMID- 28490967
TI  - Comparative study of fatty-acid composition of table eggs from the Jeddah food
      market and effect of value addition in omega-3 bio-fortified eggs.
AB  - Health consciousness has increased the desire of people around the world to
      consume functional foods. Omega-3 essential fatty acids are one among these
      beneficial and important health supplements without which a general
      predisposition to degenerative and stress related disorders can occur. Saudi
      Arabia has shown an alarming increase in obesity (Al-Nozha et al., 2005),
      diabetes (Alqurashi et al., 2011), and cardiovascular disease (Al-Nozha et al.,
      2004) in the last few decades mainly due to nutritional transitions and lifestyle
      alterations (Amuna and Zotor, 2008). Lack of nutrient dense foods and the
      prevailing food related disorder of obesity (Popkin, 2001; Prentice, 2014)
      especially render egg as a choice food to be value-added for attaining
      nutritional security in Saudi Arabia and in effect reverse the increasing
      incidences of lifestyle diseases. Nutritional intervention through a commonly
      consumed food product would be an important step in improving the health of the
      people, and reducing health care costs. As eggs are a frequently consumed food
      item in Saudi Arabia, enriching them with omega-3 fatty acids would be an
      excellent way to alleviate the existing problems. A significant deposition of
      omega-3 fatty acids in the eggs was observed when the diet of hens was
      supplemented with omega-3 fatty acids from either flaxseed or fish oil source.
      Inadequacy of omega-3 fatty acids could thus be rectified by producing omega-3
      enriched eggs from hens supplemented with flaxseed or fish oil source, and thus
      contribute toward better health choice of the consumer.

PMID- 28490968
TI  - Inhibitory activity of different medicinal extracts from Thuja leaves, ginger
      roots, Harmal seeds and turmeric rhizomes against Fig leaf mottle-associated
      virus 1 (FLMaV-1) infecting figs in Mecca region.
AB  - Fig leaf mottle-associated virus-1 (FLMaV-1) is a closterovirus newly identified
      in fig trees, in the Mecca region, suffering from mosaic disease symptoms and
      apparently is compromising the fig plantation in the country. In the present
      study, we demonstrated the efficiency of two in vivo experiments including pre
      and post treatments using Thuja leaf, ginger roots, Harmal seeds and turmeric
      rhizome extracts on symptoms expression of rooted cuttings infected with FLMaV-1-
      and their impact on virus multiplication. Results showed that individual
      treatments with ginger roots and turmeric rhizomes in pre-grafting experiments
      and Thuja extract following Harmal seeds in post grafting experiments were
      efficient against symptom development. In addition, results showed that the total
      photosynthesis pigments; total soluble intracellular proteins and total phenol
      contents were higher in infected treated cuttings compared with healthy ones,
      thus it was taken as evidence on a mutual interaction between these extracts and
      virus multiplication.

PMID- 28490969
TI  - Differential expression of six genes and correlation with fatness traits in a
      unique broiler population.
AB  - Previous results from genome wide association studies (GWASs) in chickens
      divergently selected for abdominal fat content of Northeast Agricultural
      University (NEAUHLF) showed that many single nucleotide polymorphism (SNP)
      variants were associated with abdominal fat content. Of them, six top significant
      SNPs at the genome level were located within SRD5A3, SGCZ, DLC1, GBE1, GALNT9 and
      DNAJB6 genes. Here, expression levels of these six candidate genes were
      investigated in abdominal fat and liver tissue between fat and lean broilers from
      the 14th generation population of NEAUHLF. The results showed that expression
      levels of SRD5A3, SGCZ and DNAJB6 in the abdominal fat and SRD5A3, DLC1, GALNT9,
      DNAJB6 and GBE1 in the liver tissue differed significantly between the fat and
      lean birds, and were correlated with abdominal fat traits. The findings will
      provide important references for further function investigation of the six
      candidate genes involved in abdominal fat deposition in chickens.

PMID- 28490970
TI  - Antibacterial activities of the methanol extracts of Albizia adianthifolia,
      Alchornea laxiflora, Laportea ovalifolia and three other Cameroonian plants
      against multi-drug resistant Gram-negative bacteria.
AB  - In the last 10 years, resistance in Gram-negative bacteria has been increasing.
      The present study was designed to evaluate the in vitro antibacterial activities
      of the methanol extracts of six Cameroonian medicinal plants Albizia
      adianthifolia, Alchornea laxiflora, Boerhavia diffusa, Combretum hispidum,
      Laportea ovalifolia and Scoparia dulcis against a panel of 15 multidrug resistant
      Gram-negative bacterial strains. The broth microdilution was used to determine
      the minimal inhibitory concentration (MIC) and minimal bactericidal concentration
      (MBC) of the extracts. The preliminary phytochemical screening of the extracts
      was conducted according to the reference qualitative phytochemical methods.
      Results showed that all extracts contained compounds belonging to the classes of
      polyphenols and triterpenes, other classes of chemicals being selectively
      distributed. The best antibacterial activities were recorded with bark and root
      extracts of A. adianthifolia as well as with L. ovalifolia extract, with MIC
      values ranging from 64 to 1024 MUg/mL on 93.3% of the fifteen tested bacteria.
      The lowest MIC value of 64 MUg/mL was recorded with A. laxiflora bark extract
      against Enterobacter aerogenes EA289. Finally, the results of this study provide
      evidence of the antibacterial activity of the tested plants and suggest their
      possible use in the control of multidrug resistant phenotypes.

PMID- 28490972
TI  - Intensifying responsiveness towards neglected intestinal helminth infections in a
      resource-constrained setting.
AB  - Neglected intestinal helminth infections afflict the marginalized communities in
      Asia. Since 2004, growing body of evidence in Myanmar indicated high prevalence
      of soil-transmitted helminths (STH) infections (30-40%) among school children. Co
      existence of STH (23%) with food-borne trematodes was noted among 383 pregnant
      women in a selected township in 2012-2014 followed by molecular verification of
      very low prevalence of schistosome infection (<5%) in the same study site in
      2016. The success of transmission elimination plans may depend upon sensitive
      diagnostic tools to detect persistent infections and polyparasitism. Addressing
      the research gaps in vulnerable sites requires an increased investment in
      resource-constrained settings.

PMID- 28490971
TI  - Chemoprotective effect of omega-3 fatty acids on thioacetamide induced hepatic
      fibrosis in male rats.
AB  - The current study was designed to investigate the possible protective effect of
      omega-3 fatty acids from fish oil on hepatic fibrosis induced by thioacetamide
      (TAA) in male rats. The experimental animals were divided into four groups. The
      first group was received saline solution and served as control. The second group
      was given 250 mg/kg body weight of TAA. The third group was treated with omega-3
      fatty acids and TAA. The fourth group was given saline solution and supplemented
      with omega-3 fatty acids. Treatment of rats with TAA for three and six weeks
      resulted in a significant decrease in body weight gain, while the value of
      liver/body weight ratio was statistically increased. Furthermore, the levels of
      serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase,
      gamma glutamyl transferase and total bilirubin were significantly increased.
      After three weeks of exposure to only TAA, liver sections showed an abnormal
      morphology characterized by noticeable fibrosis with the extracellular matrix
      collagen contents and damage of liver cells' structure. Liver sections from rats
      treated with only TAA for six weeks revealed an obvious increase in extracellular
      matrix collagen content and bridging fibrosis. Treating TAA-intoxicated rats with
      omega-3 fatty acids significantly attenuated the severe physiological and
      histopathological changes. Finally, the present investigation suggests that omega
      3 fatty acids could act against hepatic fibrosis induced by TAA due to its
      antioxidant properties, thus supporting its use in hepatic fibrosis therapy.

PMID- 28490973
TI  - Transnational organizing: Issue professionals in environmental sustainability
      networks.
AB  - An ongoing question for institutional theory is how organizing occurs
      transnationally, where institution building occurs in a highly ambiguous
      environment. This article suggests that at the core of transnational organizing
      is competition and coordination within professional and organizational networks
      over who controls issues. Transnational issues are commonly organized through
      professional battles over how issues are treated and what tasks are involved.
      These professional struggles are often more important than what organization has
      a formal mandate over an issue. We highlight how 'issue professionals' operate in
      two-level professional and organizational networks to control issues. This two
      level network provides the context for action in which professionals do their
      institutional work. The two-level network carries information about professional
      incentives and also norms about how issues should be treated and governed by
      organizations. Using network and career sequences methods, we provide a case of
      transnational organizing through professionals who attempt issue control and
      network management on transnational environmental sustainability certification.
      The article questions how transnational organizing happens, and how we can best
      identify attempts at issue control.

PMID- 28490974
TI  - The introduction of biosimilars of low molecular weight heparins in Europe: a
      critical review and reappraisal endorsed by the Italian Society for Haemostasis
      and Thrombosis (SISET) and the Italian Society for Angiology and Vascular
      Medicine (SIAPAV).
AB  - Recently, the European Medicines Agency (EMA) authorized the introduction and
      marketing of Thorinane(r) and Inhixa(r), biosimilars of the Low Molecular Weight
      Heparin (LMWH) enoxaparin. The authorization path is considerably different from
      the guidelines published by the EMA in 2009, as well as from the recommendations
      from the International Society on Thrombosis and Haemostasis published in 2013.
      Indeed, both of them recommended that LMWHs biosimilars therapeutic equivalence
      should be demonstrated in at least one adequately designed clinical trial.
      Shortly after enoxaparin biosimilars approval, EMA published a revised version of
      its guideline, no longer requiring the execution of a clinical study in patients
      at risk of venous thromboembolism. Also the assessment of safety shows some
      relevant flaws, as it relies only on a 20 healthy volunteers study, clearly
      underpowered to draw any conclusions about the safety profile of the drug. In our
      opinion, the approach taken by EMA for approval of enoxaparin biosimilars raises
      serious concerns about their actual, clinical "similarity". On these grounds,
      with the endorsement of the Italian Society for Haemostasis and Thrombosis
      (SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV), we
      elaborated the present document aimed at reviewing and reappraising some critical
      points regarding the introduction of biosimilars of LMWH in Europe. Moreover, we
      would strongly advise the Italian National Health Authorities not to entrust
      safety assessment to the post-marketing surveillance only, but to promote well
      designed and powered studies aimed at establish the actual efficacy and safety of
      LMWH biosimilars.

PMID- 28490975
TI  - Comparison of transepithelial resistance measurement techniques: Chopsticks vs.
      Endohm.
AB  - BACKGROUND: TER measurements across confluent cellular monolayers provide a
      useful indication of TJ strength between epithelial and endothelial cells in
      culture. Having a reliable and accurate method of measuring cell-to-cell adhesion
      is critical to studies in pathophysiology and cancer metastasis. However, the use
      of different technical approaches to measure TER has reportedly yielded
      inconsistent measurements within the same cell lines. METHODS: In the current
      study, we compared the peak TER values for the MDCK (canine kidney) and MCF-7
      (human breast cancer) epithelial cell lines using two common approaches
      (Chopstick and Endohm) and two types of polymer inserts (PC and PET). RESULTS:
      Both cell lines demonstrated a statistically significant difference in the peak
      TERs obtained using the two different approaches. Further, the MDCK (but not the
      MCF-7) cells demonstrated a statistically significant difference between the peak
      TERs when using the same approach but different inserts. CONCLUSION: Our study
      indicates the importance of using a single approach when seeking to measure and
      compare the TER values of cultured cell lines.

PMID- 28490976
TI  - Teaching Stimulus-Stimulus Relations to Minimally Verbal Individuals: Reflections
      on Technology and Future Directions.
AB  - This paper discusses recent methodological approaches and investigations that are
      aimed at developing reliable behavioral technology for teaching stimulus-stimulus
      relations to individuals who are minimally verbal and show protracted difficulty
      in acquiring such relations. The paper has both empirical and theoretical
      content. The empirical component presents recent data concerning the possibility
      of generating rapid relational learning in individuals who do not initially show
      it. The theoretical component (1) considers decades of methodological
      investigations with this population and (2) suggests a testable hypothesis
      concerning some individuals exhibit unusual difficulties in learning. Given this
      background, we suggest a way forward to better understand and perhaps resolve
      these learning challenges.

PMID- 28490977
TI  - Editorial.

PMID- 28490978
TI  - Radiobiology of stereotactic body radiation therapy (SBRT).
AB  - Recent advances in the technology of radiotherapy have enabled the development of
      new therapeutic modalities that deliver radiation with very high accuracy,
      reduced margins and high dose conformation, allowing the reduction of healthy
      tissue irradiated and therefore minimizing the risk of toxicity. The next step
      was to increase the total tumor dose using conventional fractionation (which
      remains the best way to relatively radioprotect healthy tissues when large
      volumes are treated) or to use new fractionation schemes with greater biological
      effectiveness. Based on the experience gained in radiosurgery, the latter way was
      chosen for small and well-defined tumors in the body. Stereotactic body
      radiotherapy delivers high doses of radiation to small and well-defined targets
      in an extreme hypofractionated (and accelerated) scheme with a very high
      biological effectiveness obtaining very good initial clinical results in terms of
      local tumor control and acceptable rate of late complications. In fact, we
      realize a posteriori that it was not feasible to administer such biologically
      equivalent dose in a conventional fractionation because the treatment could last
      several months. So far, these new therapeutic modalities have been developed due
      to technologic advances in image guidance and treatment delivery but without a
      solid biological basis. It is the role of traditional radiobiology (and molecular
      radiobiology) to explain the effects of high doses of ionizing radiation on tumor
      and normal tissues. Only through a better understanding of how high doses of
      ionizing radiation act, clinicians will know exactly what we do, allowing us in
      the future to refine our treatments. This article attempts to describe through
      simple and understandable concepts the known aspects of the biological action of
      high doses of radiation on tumor and normal tissues, but it is clear that we need
      much more basic research to better understand the biology of high doses of
      radiation.

PMID- 28490979
TI  - Dose to organ at risk and dose prescription in liver SBRT.
AB  - Stereotactic body radiation therapy (SBRT) is delivered in a curative intent to
      many primary and secondary tumors. Concerning liver metastasis, SBRT can be
      safely delivered using one to five fractions. An excellent local control is
      obtained with doses from 20 to 60 Gy. For primary hepatic tumors, results are
      also good, but the risk of hepatic toxicity related to liver pre-existent
      pathology must be taken into account. Radiation induced liver disease (RILD) is
      not frequent in its classical presentation, but modifications of liver enzymes
      are often observed. Other toxicities of SBRT on the duodenum, small bowel and
      biliary tract are also described. With respect to contraindications and dose
      limitations on surrounding structures, SBRT is well tolerated and takes place
      among curative treatment of liver tumors, as surgery, radiofrequency and
      embolization.

PMID- 28490980
TI  - SBRT planning for liver metastases: A focus on immobilization, motion management
      and planning imaging techniques.
AB  - AIM: To evaluate the different techniques used for liver metastases Stereotactic
      Body Radiation Therapy (SBRT) planning. We especially focused on immobilization
      devices, motion management and imaging used for contouring. BACKGROUND: Although
      some guidelines exist, there is no consensus regarding the minimal requirements
      for liver SBRT treatments. MATERIALS AND METHODS: We reviewed the main liver
      metastases SBRT publications and guidelines; and compared the techniques used for
      immobilization, motion management, margins and imaging. RESULTS: There is a wide
      variety of techniques used for immobilization, motion management and planning
      imaging. CONCLUSIONS: We provide a subjective critical analysis of minimal
      requirements and ideal technique for liver SBRT planning.

PMID- 28490981
TI  - Robotic radiosurgery for the treatment of liver metastases.
AB  - AIM: This study evaluates the toxicity and outcome in patients treated with
      robotic radiosurgery for liver metastases. BACKGROUND: Modern technologies allow
      the delivery of high doses to the liver metastases while lowering the dose to the
      neighboring organs at risk. Whether this dosimetric advantage translates into
      clinical benefit is not well known yet. METHODS AND MATERIALS: A total of 9
      patients with 17 liver metastases have been treated with robotic stereotactic
      body radiotherapy SBRT from March 2011 to December 2014. Local response to SBRT
      was graded by the Response Evaluation Criteria in Solid Tumors criteria to
      describe change in treated tumor lesion. Adverse events after SBRT were graded on
      a 1-5 scale according to the National Cancer Institute common terminology
      criteria for adverse events v4.0. RESULTS: Patients received either three (78%)
      or five (22%) fractions. Patients were treated with a mean fraction dose of 14 Gy
      with a range from 9 to 20 Gy. The median total radiation dose provided to
      patients was 45 Gy with a range of 45-60 Gy. Four out of the 17 (23.5%) treated
      lesions had a complete response, 9 (53%) partial response and 3 (17.6%) stable
      disease. With a median follow-up of 15.2 months after SBRT treatment, local
      control and overall survival rated were 89% and 66%, respectively. No patient
      experienced grade >=3 toxicity. The most common toxicity reported was asthenia.
      Only two patients had nausea and diarrhea, 10 and 14 days after SBRT,
      respectively. CONCLUSIONS: Robotic radiosurgery is a safe and effective local
      treatment option for secondary liver tumors. Further prospective studies are
      ongoing to determine long-term response and survival after robotic-SBRT for liver
      metastases.

PMID- 28490982
TI  - Radiosurgery for liver metastases. A single institution experience.
AB  - AIM: To report our initial results on the use of radiosurgery for treatment of
      liver metastases. BACKGROUND: In recent years there has been increasing interest
      in the use of stereotactic body radiation therapy to treat metastatic disease to
      the liver as an alternative to interventional procedures. MATERIALS AND METHODS:
      Between November 2008 and June 2015 a total of 36 LINAC-based radiosurgeries
      using VMAT were performed in 27 patients with liver metastases from 10 different
      primary sites. Doses ranged from 21 Gy to 60 Gy in 1 to 5 fractions. In all
      patients the volume of liver receiving less than 15 Gy was more than 700 cc. The
      volume treated with the prescription dose ranged from 1 cc to 407 cc with a
      median of 58 cc. All patients but one received systemic treatment. RESULTS:
      Overall median survival for the entire group is 9 months (ranging from 1 to 67
      months). Local recurrence free survival ranged from 4 to 67 months with a median
      of 14 months. Twenty patients (80%) survived more than six months. Three patients
      treated for oligometastases were alive after 3 years. Grade 0 toxicity was
      encountered in 22/27 patients, Grade 1 toxicity in 5/27 and only 1/27 patient
      experienced Grade 2 toxicity. No patient experienced grade 3-4 toxicity.
      CONCLUSION: Based on these initial results we conclude that SBRT for treating
      liver metastases with radiosurgery is safe and effective for treating one or
      multiple lesions as long as normal tissue constraints for liver are respected.

PMID- 28490983
TI  - Institutional experience in the treatment of colorectal liver metastases with
      stereotactic body radiation therapy.
AB  - AIM: To investigate whether the impact of dose escalation in our patient
      population represented an improvement in local control without increasing
      treatment related toxicity. MATERIALS AND METHODS: A cohort of consecutive
      patients with colorectal liver metastases treated with stereotactic body
      radiation therapy (SBRT) between December 2002 and December 2013 were eligible
      for this study. Inclusion criteria were a Karnofsky performance status >=80% and,
      according to the multidisciplinary tumor board, ineligibility for surgery or
      radiofrequency ablation. Exclusion criteria were a lesion size >6 cm, more than 3
      metastases, and treatment delivered with other fractionation scheme than 3 times
      12.5 Gy or 16.75 Gy prescribed at the 65-67% isodose. To analyze local control,
      CT or MRI scans were acquired during follow-up. Toxicity was scored using the
      Common Toxicity Criteria Adverse Events v4.0. RESULTS: A total of 40 patients
      with 55 colorectal liver metastases were included in this study. We delivered
      37.5 Gy to 32 lesions, and 50.25 Gy to 23 lesions. Median follow-up was 26 and 25
      months for these two groups. Local control at 2 and 3 years was 74 and 66% in the
      low dose group while 90 and 81% was reached in the high dose group. No
      significant difference in local control between the two dose fractionation
      schemes could be found. Grade 3 toxicity was limited and was not increased in the
      high dose group. CONCLUSIONS: SBRT for colorectal liver metastases offers a high
      chance of local control at long term. High irradiation doses may contribute to
      enhance this effect without increasing toxicity.

PMID- 28490984
TI  - Evaluation of reproducibility of tumor repositioning during multiple breathing
      cycles for liver stereotactic body radiotherapy treatment.
AB  - AIM: To evaluate the tumor repositioning during gated volumetric modulated arc
      therapy (VMAT) for liver stereotactic body radiotherapy(SBRT) treatment using
      implanted fiducial markers and intrafraction kilovoltage (kV) images acquired
      during dose delivery. MATERIALS AND METHODS: Since 2012, 47 liver cancer patients
      with implanted fiducial markers were treated using the gated VMAT technique with
      a Varian Truebeam STx linear accelerator. The fiducial markers were implanted
      inside or close to the tumor target before treatment simulation. They were
      defined at the maximum inhalation and exhalation phases on a 4-dimensionnal
      computed tomography (4DCT) acquisition. During the treatment, kV images were
      acquired just before the beam-on at each breathing cycle at maximum exhalation
      and inhalation phases to verify the fiducial markers positions. For the five
      first fractions of treatment in the first ten consecutive patients, a total of
      2705 intrafraction kV images were retrospectively analyzed to assess the
      differences between expected and actual positions of the fiducial markers along
      the cranio-caudal (CC) direction during the exhalation phase. RESULTS: The mean
      absolute intrafractional fiducial marker deviation along the CC direction was 1.0
      mm at the maximum exhalation phase. In 99%, 95% and 90% cases, the fiducial
      marker deviations were <=4.5 mm, 2.8 mm and 2.2 mm, respectively. CONCLUSION:
      Intrafraction kV images allowed us to ensure the consistency of tumor
      repositioning during treatment. In 99% cases, the fiducial marker deviations were
      <=4.5 mm corresponding to our 5 mm treatment margin. This margin seems to be well
      adapted to the gated VMAT SBRT treatment in liver disease.

PMID- 28490985
TI  - Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time
      adaptive tumor gating. Concerns about technique and preliminary clinical results.
AB  - BACKGROUND: Motion management is a major challenge in abdominal SBRT. We present
      our study of SBRT for liver tumors using intrafraction motion review (IMR)
      allowing simultaneous KV information and MV delivery to synchronize the beam
      during gated RapidArc treatment. MATERIALS AND METHODS: Between May 2012 and
      March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique
      in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding
      5 mm from the ITV. Dose prescription ranged from 40 to 50 Gy in 5-10 fractions.
      The prescribed dose and fractionation were chosen depending on hepatic function
      and dosimetric results. Thirty-four patients with a minimal follow-up of six
      months were analyzed for local control and toxicity. Accuracy for tumor
      repositioning was evaluated for the first ten patients. RESULTS: With a median
      follow-up of 13 months, the treatment was well tolerated and no patient presented
      RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3
      patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with
      G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver
      enzymes. In-field local control was 90.3% with 7 complete responses, 14 partial
      responses and 7 stabilisations. 3 patients evolved "in field". 12 patients had an
      intrahepatic progression "out of field". Mean intrafraction deviation of
      fiducials in the craneo-caudal direction was 0.91 mm (0-6 mm). CONCLUSION: The
      clinical tolerance and oncological outcomes were favorable when using image
      guided liver SBRT with real-time adaptive tumor gating.

PMID- 28490986
TI  - Image guided SBRT for multiple liver metastases with ExacTrac(r) Adaptive Gating.
AB  - AIM: To report the outcome and toxicity of sequential stereotactic body
      radiotherapy (SBRT) for multiple liver metastases in patients treated with
      ExacTrac Adaptive Gating. BACKGROUND: In selected patients with a limited number
      of liver metastases, SBRT has been evaluated as a safe and effective treatment,
      with minimal toxicity and high rates of local control. MATERIALS AND METHODS:
      From April 2008 to October 2013, 21 patients with multiple (3-14) liver
      metastases (n = 101) were treated sequentially with SBRT at our institution.
      Maximum tumor diameter was 7.5 cm. Prior to treatment, internal markers were
      placed inside or near the tumor. CT or PET-CT simulation was used for the
      definition of gross tumor volume (GTV). Median planning target volume was 32.3 cc
      (3.6-139.3 cc). Treatment consisted of 3 fractions (12-20 Gy/fraction) or 5
      fractions (10 Gy/fraction), prescribed to the 90-95% of the PTV volume. Daily
      intra-fraction image guidance was performed with ExacTrac Adaptive Gating.
      Regular follow-up included CT or PET-CT imaging. RESULTS: After a median of 23.2
      months, the estimated local control rate was 94.4%, 80.6%, 65% and 65% after 1,
      2, 3 and 4 years; the median overall survival was 62 months (95% CI 49.12-74.87)
      and the actuarial survival reached at 60 months was 57.6%. The univariate data
      analysis revealed that only primary histology other than colorectal
      adenocarcinoma was shown as an independent significant prognostic factor for
      local control (p = 0.022). Number of treated metastases did not modify
      significantly the overall survival (p = 0.51). No toxicity higher than G3 (1
      patient with chest wall pain) and no radiation-induced liver disease were
      observed. CONCLUSIONS: Sequential SBRT with ExacTrac Adaptive Gating for multiple
      liver metastases can be considered an effective, safe therapeutic option, with a
      low treatment-related toxicity. Excellent rates of local control and survival
      were obtained.

PMID- 28490987
TI  - Stereotactic body radiation therapy for liver metastasis - The linac-based
      Greater Poland Cancer Centre practice.
AB  - AIM: The main purpose of this work is to give a technical description and present
      the properties of the liver SBRT protocol implemented in the Greater Poland
      Cancer Centre (GPCC) in Poznan, Poland. BACKGROUND: Stereotactic body radiation
      therapy (SBRT) for liver metastasis is a non-invasive therapeutic option which
      enables irradiation of a small target in the body with a high dose. MATERIALS AND
      METHODS: This study presents details of our linac-based liver SBRT protocol.
      Special emphasis has been placed on fiducial implantation, patient preparation
      (CT scanning, immobilization), treatment planning, and its implementation.
      RESULTS: The liver SBRT treatment course implemented in the GPCC consists of
      three fractions to deliver a total of 45 Gy. Fraction delivery details with
      description of patient positioning (localization of liver metastasis) are
      presented below. CONCLUSIONS: The literature validation of the assumptions
      concerning the steps of the GPCC linac-based liver SBRT procedure show their
      potential for an effective and patient friendly implementation.

PMID- 28490988
TI  - The role of SBRT in oligometastatic patients with liver metastases from breast
      cancer.
AB  - Liver metastases from breast cancer are a common occurrence. Local ablative
      therapies are a promising therapeutic option for these patients, with the
      potential for a long term disease control in the setting of "oligometastatic
      patients". Identification of the perfect candidate for local approaches is still
      challenging and unclear. Stereotactic body radiation therapy (SBRT) is one of the
      most valuable local therapy, because of great efficiency, low morbidity and
      minimal invasiveness. In this paper, we reviewed the state of the art in the care
      of breast cancer patients with liver metastases, with a focus on SBRT.

PMID- 28490989
TI  - Evaluation of response after SBRT for liver tumors.
AB  - Stereotactic body radiotherapy (SBRT) has developed over the last few years for
      the treatment of primary and metastatic hepatic tumors. The tumoral and adjacent
      peritumoral modifications caused by this radiosurgery limit the evaluation of
      response by anatomic imaging and dimensional criteria alone, such as with RECIST.
      This suggests that it is of interest to also take into account the residual
      enhancement and hyper metabolism of these hepatic targets. We have reviewed the
      English language literature regarding the response of hepatic lesions treated by
      SBRT, and found that only seven articles were specifically concerned with this
      problem. The response of the hepatocellular carcinoma after SBRT has been studied
      specifically with multiphase enhanced CT-scan. Criteria set by the European
      Association of Study of the Liver better estimate response at each time point of
      follow up than RECIST does. Non-enhancement, reflecting tumor necrosis, is
      additionally an early indicator of response with extended response in time and a
      best non-enhancement percentage is observed at 12 months. The response after
      treatment by SBRT of cholangiocarcinoma has not yet generated a specific report.
      Use of RECIST criteria is also inadequate in the evaluation of response after
      SBRT for hepatic metastases. Response of liver metastases to SBRT is better
      assessed with a combination of size and enhancement pattern. The occurrence of a
      lobulated enhancement during follow up is efficient to predict local progression
      in a specific, reproducible, and sensitive way. Patients with FDG-avid hepatic
      metastases are also better evaluated with PET-CT and functional criteria than
      routine imaging and metric evaluation alone.

PMID- 28490990
TI  - Management of liver cancer. The Surgeon's point of view.
AB  - During the last twenty years, a huge progress has been achieved in the treatment
      of liver cancer and recent strategies include interventional radiology,
      chemotherapy regimens and surgery. Meanwhile, Stereotactic Body Radiation Therapy
      (SRBT) has developed in the treatment of all organs with millimetre accuracy,
      very few side effects and a high control rate. So, SRBT has become a therapeutic
      weapon in his own right in liver tumour treatment. Many publications have
      reported encouraging results in colorectal liver metastasis, hepatocellular
      carcinoma on cirrhosis and peripheric cholangiocarcinoma. It is important that
      radiation therapists involve systematic multidisciplinary "liver tumour" meetings
      to discuss therapeutic indications and initiate treatments quickly.

PMID- 28490991
TI  - Other non-surgical treatments for liver cancer.
AB  - Interventional radiology plays a major role in the modern management of liver
      cancers, in primary hepatic malignancies or metastases and in palliative or
      curative situations. Radiological treatments are divided in two categories based
      on their approach: endovascular treatment and direct transcapsular access.
      Endovascular treatments include mainly three applications: transarterial
      chemoembolization (TACE), transarterial radioembolization (TARE) and portal vein
      embolization (PVE). TACE and TARE share an endovascular arterial approach,
      consisting of a selective catheterization of the hepatic artery or its branches.
      Subsequently, either a chemotherapy (TACE) or radioembolic (TARE) agent is
      injected in the target vessel to act on the tumor. PVE raises the volume of the
      future liver remnant in extended hepatectomy by embolizing a portal vein
      territory which results in hepatic regeneration. Direct transcapsular access
      treatments involve mainly three techniques: radiofrequency thermal ablation
      (RFA), microwave thermal ablation (MWA) and percutaneous ethanol injection (PEI).
      RFA and MWA procedures are almost identical, their clinical applications are
      similar. A probe is deployed directly into the tumor to generate heat and
      coagulation necrosis. PEI has known implications based on the chemical toxicity
      of intra-tumoral injection with highly concentrated alcohol by a thin needle.

PMID- 28490992
TI  - The Contribution of Cognitive Networks to Depression in Epilepsy.
AB  - This review poses the question: Does disruption to cognitive brain networks in
      epilepsy contribute to the problem of comorbid depression? Initial evidence
      suggests that the network disease that gives rise to seizures has a predilection
      for the same cognition-related networks that regulate mood, with comorbidity
      reflective of more extensive disease. Framing both epilepsy and its psychiatric
      comorbidities in terms of dysfunction in overlapping (cognitive) networks raises
      the possibility that depression can be a primary feature of the disease in some
      cases and facilitates an epilepsy classification system where behavioral features
      of the disorder are embedded in a neurobiological mechanism.

PMID- 28490993
TI  - An mTOuR of Epilepsy in Tuberous Sclerosis Complex.

PMID- 28490994
TI  - Magnetoencephalography and Stereo-EEG Unite!

PMID- 28490995
TI  - The Malrotated Hippocampal Formation: How Often Must We Judge Function by Shape?

PMID- 28490996
TI  - Cannabidiol in Patients With Intractable Epilepsy Due to TSC: A Possible
      Medication But Not a Miracle.

PMID- 28490997
TI  - ADHD in Pediatric Epilepsy: Fact or Fiction?

PMID- 28490998
TI  - Do Patients With Temporal Lobe Epilepsy and Cognitive Decline Have Alzheimer's
      Disease or Chronic Traumatic Encephalopathy (CTE)?

PMID- 28490999
TI  - Levetiracetam in Men With Epilepsy: Testosterone Is Left Alone But Sperm Count Is
      Paramount.

PMID- 28491000
TI  - Delayed Seizures and Poor Functional Outcome After Intracranial Hemorrhage Is the
      Fate of Patients with a Poor Underlying Substrate, Say the Intensivists.

PMID- 28491001
TI  - AED Switching: A Game of Skill or a Game of Chance?

PMID- 28491002
TI  - Push and Pull: Borrowing Concepts From Control Theory for Seizure Spread.

PMID- 28491003
TI  - Theta Rhythmopathy as a Cause of Cognitive Disability in TLE.
AB  - Memory difficulties are commonly associated with temporal lobe epilepsy (TLE) and
      cause significant disability. This article reviews the role of altered
      hippocampal theta oscillations and theta-gamma coupling as potential causes of
      memory disturbance in temporal lobe epilepsy, dissecting the potential mechanisms
      underlying these changes in large-scale neuronal synchronization. We discuss
      development of treatments for cognitive dysfunction directed at restoring theta
      rhythmicity and future directions for research.

PMID- 28491004
TI  - Precision Medicine: NMDA Receptor-Targeted Therapy for GRIN2D Encephalopathy.

PMID- 28491005
TI  - Puritan's View of the "Menage a Trois".

PMID- 28491006
TI  - Glycolysis Inhibition: The Gift of GAB(A).

PMID- 28491007
TI  - Targeting Newly Generated Granule Cells: A Double-Edged Sword.

PMID- 28491008
TI  - Decision Support System Requirements Definition for Human Extravehicular Activity
      Based on Cognitive Work Analysis.
AB  - The design and adoption of decision support systems within complex work domains
      is a challenge for cognitive systems engineering (CSE) practitioners,
      particularly at the onset of project development. This article presents an
      example of applying CSE techniques to derive design requirements compatible with
      traditional systems engineering to guide decision support system development.
      Specifically, it demonstrates the requirements derivation process based on
      cognitive work analysis for a subset of human spaceflight operations known as
      extravehicular activity. The results are presented in two phases. First, a work
      domain analysis revealed a comprehensive set of work functions and constraints
      that exist in the extravehicular activity work domain. Second, a control task
      analysis was performed on a subset of the work functions identified by the work
      domain analysis to articulate the translation of subject matter states of
      knowledge to high-level decision support system requirements. This work
      emphasizes an incremental requirements specification process as a critical
      component of CSE analyses to better situate CSE perspectives within the early
      phases of traditional systems engineering design.

PMID- 28491009
TI  - Simplified Approach Charts Improve Data Retrieval Performance.
AB  - The effectiveness of different instrument approach charts to deliver minimum
      visibility and altitude information during airport equipment outages was
      investigated. Eighteen pilots flew simulated instrument approaches in three
      conditions: (a) normal operations using a standard approach chart (standard
      normal), (b) equipment outage conditions using a standard approach chart
      (standard-outage), and (c) equipment outage conditions using a prototype
      decluttered approach chart (prototype-outage). Errors and retrieval times in
      identifying minimum altitudes and visibilities were measured. The standard-outage
      condition produced significantly more errors and longer retrieval times versus
      the standard-normal condition. The prototype-outage condition had significantly
      fewer errors and shorter retrieval times than did the standard-outage condition.
      The prototype-outage condition produced significantly fewer errors but similar
      retrieval times when compared with the standard-normal condition. Thus, changing
      the presentation of minima may reduce risk and increase safety in instrument
      approaches, specifically with airport equipment outages.

PMID- 28491010
TI  - Integrating Multidisciplinary Results to Produce New Knowledge About the
      Physician-Patient Relationship: A Methodology Applied to the INTERMEDE Project.
AB  - The INTERMEDE Project brought together a number of research teams to study the
      interaction between a patient and their general practitioner, and how this can
      produce social inequalities in health. The ultimate objective of the project was
      to formalize a core of common findings by integrating qualitative and
      quantitative results. The methodology chosen for the integration was inspired by
      the Delphi participatory method. It involves several rounds of questions and
      feedback in writing between all members of project teams, in order to compare
      contradictory opinions and identify key concepts arising from the project. This
      interdisciplinary research has provided a more nuanced understanding of the
      mechanisms underlying physician-patient interaction by revealing the convergences
      of the various disciplinary approaches.

PMID- 28491011
TI  - An integrated proteomic and glycoproteomic approach uncovers differences in
      glycosylation occupancy from benign and malignant epithelial ovarian tumors.
AB  - BACKGROUND: Epithelial ovarian carcinomas encompass a heterogeneous group of
      diseases with a poor 5-year survival rate. Serous carcinoma is the most common
      type. Most FDA-approved serum tumor markers are glycoproteins. These
      glycoproteins on cell surface or shed into the bloodstream could serve as
      therapeutic targets as well as surrogates of tumor. In addition to glycoprotein
      expressions, the analysis of protein glycosylation occupancy could be important
      for the understanding of cancer biology as well as the identification of
      potential glycoprotein changes in cancer. In this study, we used an integrated
      proteomics and glycoproteomics approach to analyze global glycoprotein abundance
      and glycosylation occupancy for proteins from high-grade ovarian serous carcinoma
      (HGSC) and serous cystadenoma, a benign epithelial ovarian tumor, by using LC
      MS/MS-based technique. METHODS: Fresh-frozen ovarian HGSC tissues and benign
      serous cystadenoma cases were quantitatively analyzed using isobaric tags for
      relative and absolute quantitation for both global and glycoproteomic analyses by
      two dimensional fractionation followed by LC-MS/MS analysis using a Orbitrap
      Velos mass spectrometer. RESULTS: Proteins and N-linked glycosite-containing
      peptides were identified and quantified using the integrated global proteomic and
      glycoproteomic approach. Among the identified N-linked glycosite-containing
      peptides, the relative abundances of glycosite-containing peptide and the
      glycoprotein levels were compared using glycoproteomic and proteomic data. The
      glycosite-containing peptides with unique changes in glycosylation occupancies
      rather than the protein expression levels were identified. CONCLUSION: In this
      study, we presented an integrated proteomics and glycoproteomics approach to
      identify changes of glycoproteins in protein expression and glycosylation
      occupancy in HGSC and serous cystadenoma and determined the changes of
      glycosylation occupancy that are associated with malignant and benign tumor
      tissues. Specific changes in glycoprotein expression or glycosylation occupancy
      have the potential to be used in the discrimination between benign and malignant
      epithelial ovarian tumors and to improve our understanding of ovarian cancer
      biology.

PMID- 28491012
TI  - Are Alpha-2D Adrenoceptor Subtypes Involved in Rat Mydriasis Evoked by New
      Imidazoline Derivatives: Marsanidine and 7-Methylmarsanidine?
AB  - The imidazoline compounds may produce mydriasis after systemic administration to
      some species (rats, cats, and mice). In mydriatic activity of imidazolines,
      alpha2D-adrenoceptors subtype(s) seems to be involved. In this study, the pupil
      dilatory effect evoked by 2 newly synthesized imidazoline derivatives-alpha2
      adrenoceptor agonists: marsanidine and 7-methylmarsanidine-was compared. The
      compounds were tested alone as well as in the presence of alpha2-adrenoceptor
      antagonists (nonselective, yohimbine, and selective toward the following alpha2
      adrenoceptor subtypes-alpha2A-2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3
      dihydro-1-methyl-1H-isoindole maleate (BRL44408), alpha2B-2-[2-(4-(2
      methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione
      dihydrochloride (ARC239), alpha2C-JP1302, alpha2D-2-(2,3-dihydro-2-methoxy-1,4
      benzodioxin-2-yl)-4,5-dihydro-1H-imidazole hydrochloride [RX821002]). The
      agonists were studied in male Wistar rats and were administered intravenously in
      cumulative doses. The antagonistic compounds were given in a single dose before
      the experiment with marsanidine or 7-methylmarsanidine. Pupil diameter was
      measured with stereoscopic microscope equipped in green light filter. Marsanidine
      and 7-methylmarsanidine exerted marked mydriatic effects. BRL44408, JP1302, and
      ARC239 did not cause significant parallel shift to the right of the dose-effect
      curves obtained for both imidazolines. In case of yohimbine and RX821002, the
      marked parallel shifts of dose-response curves were observed, with the
      antagonistic effects of RX821002 more pronounced. In vivo pharmacodynamics
      experiment suggests that alpha2D-adrenoceptor subtype is mainly engaged in
      mydriatic effects evoked in rats by imidazoline derivatives, in particular by
      clonidine.

PMID- 28491014
TI  - Decision Support System for Lymphoma Classification.
AB  - The diffuse lymphoma is a malignant tumor of lymphoid tissues. It is associated
      with abnormal, unlimited and uncontrolled proliferation of lymphoid cells. Until
      now, expert pathologists have identified diffuse lymphoma cells disease manually.
      This paper introduces automatic system with a friendly user interface to
      differentiate between the categories of the diffuse lymphoma cells. This research
      is based on the morphological features such as size, perimeter and circularity.
      The cell size is a critical element in the classification of diffuse lymphoma
      according to international formulation standards. Therefore, the applied
      procedures identify lymphoid cell population in digital microscopic images. The
      cells are classified using their morphological data according to the
      characteristics of each cell such as: circularity, perimeter, area, and color
      density. The number of cells is taken into consideration in the developed
      approach. Image processing techniques are applied to digital microscopic images
      to measure morphological parameters and to overcome image problems such as
      overlapping and cell distortion that affect the sensitivity of the measured data.
      The developed procedures help the pathologists to come to a decision regarding
      the classification of diffuse lymphoma. Moreover, it can be used to train medical
      students and young pathologists.

PMID- 28491013
TI  - Peptides with 6-Aminohexanoic Acid: Synthesis and Evaluation as Plasmin
      Inhibitors.
AB  - Fifteen new peptide derivatives of E-aminocaproic acid (EACA) containing the
      known fragment -Ala-Phe-Lys- with an affinity for plasmin were synthesised in the
      present study. The synthesis was carried out a solid phase. The following
      compounds were synthesised: H-Phe-Lys-EACA-X, H-d-Ala-Phe-Lys-EACA-X, H-Ala-Phe
      Lys-EACA-X, H-d-Ala-Phe-EACA-X and H-Ala-Phe-EACA-X, where X = OH, NH2 and NH
      (CH2)5-NH2. All peptides, except for those containing the sequence H-Ala-Phe-EACA
      X, displayed higher inhibitory activity against plasmin than EACA. The most
      active and selective inhibitor of plasmin was the compound H-d-Ala-Phe-Lys-EACA
      NH2 which inhibited the amidolytic activity of plasmin (IC50 = 0.02 mM), with the
      antifibrinolytic activity weaker than EACA. The resulting peptides did not affect
      the viability of fibroblast cells, colon cancer cell line DLD-1, breast MCF-7 and
      MDA-MB-231 cell lines.

PMID- 28491015
TI  - Protocols for Visually Guided Navigation Assessment of Efficacy of Retina
      Directed Cell or Gene Therapy in Canines.
AB  - There has been marked progress in recent years in developing gene delivery
      approaches for the treatment of inherited blinding diseases. Many of the proof-of
      concept studies have utilized rodent models of retinal degeneration. In those
      models, tests of visual function include a modified water maze swim test,
      optokinetic nystagmus, and light-dark activity assays. Test paradigms used in
      rodents can be difficult to replicate in large animals due to their size and
      awareness of non-visual aspects of the test system. Two types of visual behavior
      assays have been utilized in canines: an obstacle avoidance course and a forced
      choice Y maze. Given the progress in developing cell and gene therapies in large
      animals, such tests will become more and more valuable. This study provides
      guidelines for carrying out such tests and assesses the challenges and benefits
      associated with each test.

PMID- 28491016
TI  - A Channel Rejection Method for Attenuating Motion-Related Artifacts in EEG
      Recordings during Walking.
AB  - Recording scalp electroencephalography (EEG) during human motion can introduce
      motion artifacts. Repetitive head movements can generate artifact patterns across
      scalp EEG sensors. There are many methods for identifying and rejecting bad
      channels and independent components from EEG datasets, but there is a lack of
      methods dedicated to evaluate specific intra-channel amplitude patterns for
      identifying motion-related artifacts. In this study, we proposed a template
      correlation rejection (TCR) as a novel method for identifying and rejecting EEG
      channels and independent components carrying motion-related artifacts. We
      recorded EEG data from 10 subjects during treadmill walking. The template
      correlation rejection method consists of creating templates of amplitude patterns
      and determining the fraction of total epochs presenting relevant correlation to
      the template. For EEG channels, the template correlation rejection removed
      channels presenting the majority of epochs (>75%) correlated to the template, and
      presenting pronounced amplitude in comparison to all recorded channels. For
      independent components, the template correlation rejection removed components
      presenting the majority of epochs correlated to the template. Evaluation of scalp
      maps and power spectra confirmed low neural content for the rejected components.
      We found that channels identified for rejection contained ~60% higher delta
      power, and had spectral properties locked to the gait phases. After rejecting the
      identified channels and running independent component analysis on the EEG
      datasets, the proposed method identified 4.3 +/- 1.8 independent components (out
      of 198 +/- 12) with substantive motion-related artifacts. These results indicate
      that template correlation rejection is an effective method for rejecting EEG
      channels contaminated with motion-related artifact during human locomotion.

PMID- 28491017
TI  - Opinion: Inhibition of Blood-Brain Barrier Repair as a Mechanism in HIV-1
      Disease.

PMID- 28491018
TI  - Transcranial Stimulation of the Orbitofrontal Cortex Affects Decisions about
      Magnocellular Optimized Stimuli.
AB  - Visual categorization plays an important role in fast and efficient information
      processing; still the neuronal basis of fast categorization has not been
      established yet. There are two main hypotheses known; both agree that primary,
      global impressions are based on the information acquired through the
      magnocellular pathway (MC). It is unclear whether this information is available
      through the MC that provides information (also) for the ventral pathway or
      through top-down mechanisms by connections between the dorsal pathway and the
      ventral pathway via the frontal cortex. To clarify this, a categorization task
      was performed by 48 subjects; they had to make decisions about objects' sizes. We
      created stimuli specific to the magno- and parvocellular pathway (PC) on the
      basis of their spatial frequency content. Transcranial direct-current stimulation
      was used to assess the role of frontal areas, a target of the MC. Stimulation did
      not bias the accuracy of decisions when stimuli optimized for the PC were used.
      In the case of stimuli optimized for the MC, anodal stimulation improved the
      subjects' accuracy in the behavioral test, while cathodal stimulation impaired
      accuracy. Our results support the hypothesis that fast visual categorization
      processes rely on top-down mechanisms that promote fast predictions through
      coarse information carried by MC via the orbitofrontal cortex.

PMID- 28491020
TI  - Corrigendum: Structural Brain Network Reorganization and Social Cognition Related
      to Adverse Perinatal Condition from Infancy to Early Adolescence.
AB  - [This corrects the article on p. 560 in vol. 10, PMID: 28008304.].

PMID- 28491021
TI  - Corrigendum: Brain Metabolic Changes in Rats following Acoustic Trauma.
AB  - [This corrects the article on p. 148 in vol. 11, PMID: 28392756.].

PMID- 28491019
TI  - Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular
      Hypertension.
AB  - Glaucoma, one of the leading causes of blindness worldwide, affects primarily
      retinal ganglion cells (RGCs) and their axons. The pathophysiology of glaucoma is
      not fully understood, but it is currently believed that damage to RGC axons at
      the optic nerve head plays a major role. Rodent models to study glaucoma include
      those that mimic either ocular hypertension or optic nerve injury. Here we review
      the anatomical loss of the general population of RGCs (that express Brn3a;
      Brn3a+RGCs) and of the intrinsically photosensitive RGCs (that express
      melanopsin; m+RGCs) after chronic (LP-OHT) or acute (A-OHT) ocular hypertension
      and after complete intraorbital optic nerve transection (ONT) or crush (ONC). Our
      studies show that all of these insults trigger RGC death. Compared to Brn3a+RGCs,
      m+RGCs are more resilient to ONT, ONC, and A-OHT but not to LP-OHT. There are
      differences in the course of RGC loss both between these RGC types and among
      injuries. An important difference between the damage caused by ocular
      hypertension or optic nerve injury appears in the outer retina. Both axotomy and
      LP-OHT induce selective loss of RGCs but LP-OHT also induces a protracted loss of
      cone photoreceptors. This review outlines our current understanding of the
      anatomical changes occurring in rodent models of glaucoma and discusses the
      advantages of each one and their translational value.

PMID- 28491022
TI  - Corrigendum: Auditory Spatial Recalibration in Congenital Blind Individuals.
AB  - [This corrects the article on p. 76 in vol. 11, PMID: 28261053.].

PMID- 28491023
TI  - Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5-
      Supporting Cells in the Mouse Cochlea.
AB  - Cochlear supporting cells (SCs) have been shown to be a promising resource for
      hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have
      reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are
      considered to be inner ear progenitor cells. Lgr5+ progenitors are able to
      regenerate more HCs than Lgr5- SCs, and it is important to understand the
      mechanism behind the proliferation and HC regeneration of these progenitors.
      Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2
      CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+
      progenitors had significantly higher proliferation and HC regeneration ability
      than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression
      profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were
      enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we
      found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway
      genes that were uniquely expressed in one population but not the other. Last, we
      made a protein-protein interaction network to further analyze the role of these
      differentially expressed genes. In conclusion, we present a set of genes that
      might regulate the proliferation and HC regeneration ability of Lgr5+
      progenitors, and these might serve as potential new therapeutic targets for HC
      regeneration.

PMID- 28491025
TI  - Change of Rin1 and Stathmin in the Animal Model of Traumatic Stresses.
AB  - The molecular mechanism of fear memory is poorly understood. Therefore, the
      pathogenesis of post-traumatic stress disorder (PTSD), whose symptom presentation
      can enhance fear memory, remains largely unclear. Recent studies with knockout
      animals have reported that Rin1 and stathmin regulate fear memory. Rin1 inhibits
      acquisition and promotes memory extinction, whereas stathmin regulates innate and
      basal fear. The aim of our study was to examine changes in the expression of Rin1
      and stathmin in different animal models of stress, particluarly traumatic stress.
      We used three animal traumatic stresses: single prolonged stress (SPS, which is a
      rodent model of PTSD), an immobilization-stress (IM) and a Loud sound stress
      (LSS), to examine the change and uniqueness in Rin1/stathmin expression.
      Behavioral tests of SPS rats demonstrated increased anxiety and contextual fear
      conditioning. They showed decreased long-term potentiation (LTP), as well as
      decreased stathmin and increased Rin1 expression in the hippocampus and the
      amygdala. Expression of the stathmin effector, tubulin, and downstream molecules
      Rin1, Rab5, and Abl, appeared to increase. Rin1 and EphA4 were endogenously
      coexpressed in primary neurons after SPS stimulation. IM rats exhibited increased
      anxiety behavior and enhanced fear-conditioning to contextual and auditory
      stimuli. Similar changes in expression of Rin1/stathmin were observed in IM rats
      whereas no changes were observed in rats exposed to a loud sound. These data
      suggest that changes in expression of the Rin1 and stathmin genes may be involved
      in rodents with SPS and IM stresses, which provide valuable insight into fear
      memories under abnormal conditions, particularly in PTSD.

PMID- 28491024
TI  - The Serotonin Transporter and Early Life Stress: Translational Perspectives.
AB  - The interaction between the serotonin transporter (SERT) linked polymorphic
      region (5-HTTLPR) and adverse early life stressing (ELS) events is associated
      with enhanced stress susceptibility and risk to develop mental disorders like
      major depression, anxiety, and aggressiveness. In particular, human short allele
      carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the
      rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/-) show several
      similarities to the human S-allele carrier, therefore creating an animal model of
      the human situation. Many rodent studies investigated ELS interactions in SERT
      knockout rodents combined with ELS. However, underlying neuromolecular mechanisms
      of the (mal)adaptive responses to adversity displayed by SERT rodents remain to
      be elucidated. Here, we provide a comprehensive review including studies
      describing mechanisms underlying SERT variation * ELS interactions in rodents.
      Alterations at the level of translation and transcription but also epigenetic
      alterations considerably contribute to underlying mechanisms of SERT variation *
      ELS interactions. In particular, SERT+/- rodents exposed to adverse early rearing
      environment may be of high translational and predictive value to the more stress
      sensitive human short-allele carrier, considering the similarity in neurochemical
      alterations. Therefore, SERT+/- rodents are highly relevant in research that aims
      to unravel the complex psychopathology of mental disorders. So far, most studies
      fail to show solid evidence for increased vulnerability to develop affective-like
      behavior after ELS in SERT+/- rodents. Several reasons may underlie these
      failures, e.g., (1) stressors used might not be optimal or severe enough to
      induce maladaptations, (2) effects in females are not sufficiently studied, and
      (3) few studies include both behavioral manifestations and molecular correlates
      of ELS-induced effects in SERT+/- rodents. Of course, one should not exclude the
      (although unlikely) possibility of SERT+/- rodents not being sensitive to ELS. In
      conclusion, future studies addressing ELS-induced effects in the SERT+/- rodents
      should extensively study both long-term behavioral and (epi)genetic aspects in
      both sexes. Finally, further research is warranted using more severe stressors in
      animal models. From there on, we should be able to draw solid conclusions whether
      the SERT+/- exposed to ELS is a suitable translational animal model for studying
      5-HTTLPR polymorphism and stress interactions.

PMID- 28491026
TI  - "Neural Efficiency" of Athletes' Brain during Visuo-Spatial Task: An fMRI Study
      on Table Tennis Players.
AB  - Long-term training leads experts to develop a focused and efficient organization
      of task-related neural networks. "Neural efficiency" hypothesis posits that
      neural activity is reduced in experts. Here we tested the following working
      hypotheses: compared to non-athletes, athletes showed lower cortical activation
      in task-sensitive brain areas during the processing of sports related and sports
      unrelated visuo-spatial tasks. To address this issue, cortical activation was
      examined with fMRI in 14 table tennis athletes and 14 non-athletes while
      performing the visuo-spatial tasks. Behavioral results showed that athletes
      reacted faster than non-athletes during both types of the tasks, and no accuracy
      difference was found between athletes and non-athletes. fMRI data showed that,
      athletes exhibited less brain activation than non-athletes in the bilateral
      middle frontal gyrus, right middle orbitofrontal area, right supplementary motor
      area, right paracentral lobule, right precuneus, left supramarginal gyrus, right
      angular gyrus, left inferior temporal gyrus, left middle temporal gyrus,
      bilateral lingual gyrus and left cerebellum crus. No region was significantly
      more activated in the athletes than in the non-athletes. These findings possibly
      suggest that long-standing training prompt athletes develop a focused and
      efficient organization of task-related neural networks, as a possible index of
      "neural efficiency" in athletes engaged in visuo-spatial tasks, and this
      functional reorganization is possibly task-specific.

PMID- 28491027
TI  - Post-Learning Sleep Transiently Boosts Context Specific Operant Extinction
      Memory.
AB  - Operant extinction is learning to supress a previously rewarded behavior. It is
      known to be strongly associated with the specific context in which it was
      acquired, which limits the therapeutic use of operant extinction in behavioral
      treatments, e.g., of addiction. We examined whether sleep influences contextual
      memory of operant extinction over time, using two different recall tests (Recent
      and Remote). Rats were trained in an operant conditioning task (lever press) in
      context A, then underwent extinction training in context B, followed by a 3-h
      retention period that contained either spontaneous morning sleep, morning sleep
      deprivation, or spontaneous evening wakefulness. A recall test was performed
      either immediately after the 3-h experimental retention period (Recent recall) or
      after 48 h (Remote), in the extinction context B and in a novel context C. The
      two main findings were: (i) at the Recent recall test, sleep in comparison with
      sleep deprivation and spontaneous wakefulness enhanced extinction memory but,
      only in the extinction context B; (ii) at the Remote recall, extinction
      performance after sleep was enhanced in both contexts B and C to an extent
      comparable to levels at Recent recall in context B. Interestingly, extinction
      performance at Remote recall was also improved in the sleep deprivation groups in
      both contexts, with no difference to performance in the sleep group. Our results
      suggest that 3 h of post-learning sleep transiently facilitate the context
      specificity of operant extinction at a Recent recall. However, the improvement
      and contextual generalization of operant extinction memory observed in the long
      term, i.e., after 48 h, does not require immediate post-learning sleep.

PMID- 28491028
TI  - Resting-State Functional Connectivity and Network Analysis of Cerebellum with
      Respect to Crystallized IQ and Gender.
AB  - During the last years, it has been established that the prefrontal and posterior
      parietal brain lobes, which are mostly related to intelligence, have many
      connections to cerebellum. However, there is a limited research investigating
      cerebellum's relationship with cognitive processes. In this study, the network of
      cerebellum was analyzed in order to investigate its overall organization in
      individuals with low and high crystallized Intelligence Quotient (IQ). Functional
      magnetic resonance imaging (fMRI) data were selected from 136 subjects in resting
      state from the Human Connectome Project (HCP) database and were further separated
      into two IQ groups composed of 69 low-IQ and 67 high-IQ subjects. Cerebellum was
      parcellated into 28 lobules/ROIs (per subject) using a standard cerebellum
      anatomical atlas. Thereafter, correlation matrices were constructed by computing
      Pearson's correlation coefficients between the average BOLD time-series for each
      pair of ROIs inside the cerebellum. By computing conventional graph metrics,
      small-world network properties were verified using the weighted clustering
      coefficient and the characteristic path length for estimating the trade-off
      between segregation and integration. In addition, a connectivity metric was
      computed for extracting the average cost per network. The concept of the Minimum
      Spanning Tree (MST) was adopted and implemented in order to avoid methodological
      biases in graph comparisons and retain only the strongest connections per
      network. Subsequently, six global and three local metrics were calculated in
      order to retrieve useful features concerning the characteristics of each MST.
      Moreover, the local metrics of degree and betweenness centrality were used to
      detect hubs, i.e., nodes with high importance. The computed set of metrics gave
      rise to extensive statistical analysis in order to examine differences between
      low and high-IQ groups, as well as between all possible gender-based group
      combinations. Our results reveal that both male and female networks have small
      world properties with differences in females (especially in higher IQ females)
      indicative of higher neural efficiency in cerebellum. There is a trend toward the
      same direction in men, but without significant differences. Finally, three
      lobules showed maximum correlation with the median response time in low-IQ
      individuals, implying that there is an increased effort dedicated locally by this
      population in cognitive tasks.

PMID- 28491029
TI  - Sample Entropy, Univariate, and Multivariate Multi-Scale Entropy in Comparison
      with Classical Postural Sway Parameters in Young Healthy Adults.
AB  - The present study aimed to compare various entropy measures to assess the
      dynamics and complexity of center of pressure (COP) displacements. Perturbing
      balance tests are often used in healthy subjects to imitate either pathological
      conditions or to test the sensitivity of postural analysis techniques. Eleven
      healthy adult subjects were asked to stand in normal stance in three experimental
      conditions while the visuo-kinesthetic input was altered. COP displacement was
      recorded using a force plate. Three entropy measures [Sample Entropy (SE), Multi
      Scale Entropy (MSE), and Multivariate Multi Scale Entropy (MMSE)] describing COP
      regularity at different scales were compared to traditional measures of COP
      variability. The analyses of the COP trajectories revealed that suppression of
      vision produced minor changes in COP displacement and in the COP characteristics.
      The comparison with the reference analysis showed that the entropy measures
      analysis techniques are more sensitive in the incremented time series compared to
      the classical parameters and entropy measures of original time series. Non-linear
      methods appear to be an additional valuable tool for analysis of the dynamics of
      posture especially when applied on incremental time series.

PMID- 28491030
TI  - The Encephalophone: A Novel Musical Biofeedback Device using Conscious Control of
      Electroencephalogram (EEG).
AB  - A novel musical instrument and biofeedback device was created using
      electroencephalogram (EEG) posterior dominant rhythm (PDR) or mu rhythm to
      control a synthesized piano, which we call the Encephalophone. Alpha-frequency (8
      12 Hz) signal power from PDR in the visual cortex or from mu rhythm in the motor
      cortex was used to create a power scale which was then converted into a musical
      scale, which could be manipulated by the individual in real time. Subjects could
      then generate different notes of the scale by activation (event-related
      synchronization) or de-activation (event-related desynchronization) of the PDR or
      mu rhythms in visual or motor cortex, respectively. Fifteen novice normal
      subjects were tested in their ability to hit target notes presented within a 5
      min trial period. All 15 subjects were able to perform more accurately (average
      of 27.4 hits, 67.1% accuracy for visual cortex/PDR signaling; average of 20.6
      hits, 57.1% accuracy for mu signaling) than a random note generation (19.03%
      accuracy). Moreover, PDR control was significantly more accurate than mu control.
      This shows that novice healthy individuals can control music with better accuracy
      than random, with no prior training on the device, and that PDR control is more
      accurate than mu control for these novices. Individuals with more years of
      musical training showed a moderate positive correlation with more PDR accuracy,
      but not mu accuracy. The Encephalophone may have potential applications both as a
      novel musical instrument without requiring movement, as well as a potential
      therapeutic biofeedback device for patients suffering from motor deficits (e.g.,
      amyotrophic lateral sclerosis (ALS), brainstem stroke, traumatic amputation).

PMID- 28491031
TI  - Control of Absence Seizures by the Thalamic Feed-Forward Inhibition.
AB  - As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed
      to be caused by pathological interactions within the corticothalamic (CT) system.
      Using a biophysical mean-field model of the CT system, we demonstrate here that
      the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the
      cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the
      specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx,
      may participate in controlling absence seizures. In particular, we show that
      increasing the excitatory Ctx-TRN coupling strength can significantly suppress
      typical electrical activities during absence seizures. Further, investigation
      demonstrates that the GABAA- and GABAB-mediated inhibitions in the TRN-SRN
      pathway perform combination roles in the regulation of absence seizures. Overall,
      these results may provide an insightful mechanistic understanding of how the
      thalamic FFI serves as an intrinsic regulator contributing to the control of
      absence seizures.

PMID- 28491033
TI  - Corrigendum: A Mixed-Methods Trial of Broad Band Noise and Nature Sounds for
      Tinnitus Therapy: Group and Individual Responses Modeled under the Adaptation
      Level Theory of Tinnitus.
AB  - [This corrects the article on p. 44 in vol. 9, PMID: 28337139.].

PMID- 28491032
TI  - Topological Filtering of Dynamic Functional Brain Networks Unfolds Informative
      Chronnectomics: A Novel Data-Driven Thresholding Scheme Based on Orthogonal
      Minimal Spanning Trees (OMSTs).
AB  - The human brain is a large-scale system of functionally connected brain regions.
      This system can be modeled as a network, or graph, by dividing the brain into a
      set of regions, or "nodes," and quantifying the strength of the connections
      between nodes, or "edges," as the temporal correlation in their patterns of
      activity. Network analysis, a part of graph theory, provides a set of summary
      statistics that can be used to describe complex brain networks in a meaningful
      way. The large-scale organization of the brain has features of complex networks
      that can be quantified using network measures from graph theory. The adaptation
      of both bivariate (mutual information) and multivariate (Granger causality)
      connectivity estimators to quantify the synchronization between multichannel
      recordings yields a fully connected, weighted, (a)symmetric functional
      connectivity graph (FCG), representing the associations among all brain areas.
      The aforementioned procedure leads to an extremely dense network of tens up to a
      few hundreds of weights. Therefore, this FCG must be filtered out so that the
      "true" connectivity pattern can emerge. Here, we compared a large number of well
      known topological thresholding techniques with the novel proposed data-driven
      scheme based on orthogonal minimal spanning trees (OMSTs). OMSTs filter brain
      connectivity networks based on the optimization between the global efficiency of
      the network and the cost preserving its wiring. We demonstrated the proposed
      method in a large EEG database (N = 101 subjects) with eyes-open (EO) and eyes
      closed (EC) tasks by adopting a time-varying approach with the main goal to
      extract features that can totally distinguish each subject from the rest of the
      set. Additionally, the reliability of the proposed scheme was estimated in a
      second case study of fMRI resting-state activity with multiple scans. Our results
      demonstrated clearly that the proposed thresholding scheme outperformed a large
      list of thresholding schemes based on the recognition accuracy of each subject
      compared to the rest of the cohort (EEG). Additionally, the reliability of the
      network metrics based on the fMRI static networks was improved based on the
      proposed topological filtering scheme. Overall, the proposed algorithm could be
      used across neuroimaging and multimodal studies as a common computationally
      efficient standardized tool for a great number of neuroscientists and physicists
      working on numerous of projects.

PMID- 28491034
TI  - Corrigendum: Hearing Impairment Is Associated with Smaller Brain Volume in Aging.
AB  - [This corrects the article on p. 2 in vol. 9, PMID: 28163683.].

PMID- 28491035
TI  - Proteomic Analysis Reveals Autophagy as Pro-Survival Pathway Elicited by Long
      Term Exposure with 5-Azacitidine in High-Risk Myelodysplasia.
AB  - Azacytidine (5-AZA) is the standard first-choice treatment for high-risk
      myelodysplasia (MDS) patients. However, the clinical outcome for those patients
      who interrupt treatment or whose disease failed to respond is very poor. In order
      to identify the cellular pathways that are modified by long-term exposure to 5
      AZA, we evaluated key proteins associated with the autophagy pathway by reverse
      phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs)
      obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an
      increased autophagy signaling. We then evaluated ex-vivo the effect of the
      combination of 5-AZA with autophagy inhibitors chloroquine (CQ) and leupeptin.
      Since 5-AZA and CQ showed synergism due to an increase of basal autophagy after 5
      AZA exposure, we adopted a sequential treatment treating BMMCs with 5 MUM 5-AZA
      for 72 h followed by 10 MUM CQ for 24 h and found increased apoptosis, associated
      to a reduction of G2M phase and increase in G0-G1 phase. Long-term exposure to 5
      AZA induced the reduction of the autophagic marker SQSTM1/p62, reversible by CQ
      or leupeptin exposure. In conclusion, we identified autophagy as a compensatory
      pathway occurring in MDS-BM after long-term exposure to 5-AZA and we provided
      evidences that a sequential treatment of 5-AZA followed by CQ could improve 5-AZA
      efficacy, providing novel insight for tailored therapy in MDS patients
      progressing after 5-AZA therapy.

PMID- 28491036
TI  - Pharmacological Activity and Clinical Use of PDRN.
AB  - PDRN is a proprietary and registered drug that possesses several activities:
      tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic
      properties suggest its use in regenerative medicine and in diabetic foot ulcers.
      PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging
      between 50 and 1,500 KDa, it is derived from a controlled purification and
      sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta
      (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein
      and peptides that may cause immune reactions. In vitro and in vivo experiments
      have suggested that PDRN most relevant mechanism of action is the engagement of
      adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers
      nucleosides and nucleotides for the so called "salvage pathway." The binding to
      adenosine A2A receptors is a unique property of PDRN and seems to be linked to
      DNA origin, molecular weight and manufacturing process. In this context, PDRN
      represents a new advancement in the pharmacotherapy. In fact adenosine and
      dipyridamole are non-selective activators of adenosine receptors and they may
      cause unwanted side effects; while regadenoson, the only other A2A receptor
      agonist available, has been approved by the FDA as a pharmacological stress agent
      in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a
      mixture of oligonucleotides, has different molecular weight, a DNA of different
      origin and does not share the same wound healing stimulating effects of PDRN. The
      present review analyses the more relevant experimental and clinical evidences
      carried out to characterize PDRN therapeutic effects.

PMID- 28491037
TI  - Sodium 4-Carboxymethoxyimino-(4-HPR) a Novel Water-Soluble Derivative of 4-Oxo-4
      HPR Endowed with In Vivo Anticancer Activity on Solid Tumors.
AB  - 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), an active polar metabolite of
      the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR), was shown to exert
      promising antitumor activity through at least two independent mechanisms of
      action. Specifically, differently from 4-HPR and other retinoids, 4-oxo-4-HPR
      targets microtubules and inhibits tubulin polymerization causing mitotic arrest
      and on the other hand, analogously to the parent drug, it induces apoptosis
      through the activation of a signaling cascade involving the generation of
      reactive oxygen species (ROS). However, the potential in vivo use of 4-oxo-4-HPR
      is impaired by its poor solubility. By chemical modification of 4-oxo-4-HPR, a
      new class of compounds with improved solubility and in vivo bioavailability was
      obtained. We demonstrated here that, among them, the most promising molecule,
      sodium 4-carboxymethoxyimino-(4-HPR), was endowed with in vitro antitumor
      efficacy and entirely preserved the double mechanism of action of the parent drug
      in cancer cells of different histotypes. In fact, the retinoid induced the
      activation of the apoptotic cascade related to the generation of ROS through
      endoplasmic reticulum stress response and upregulation of phospho c-Jun N
      terminal kinases and PLAcental Bone morphogenetic protein, leading to cell death
      through caspase-3 cleavage. Otherwise, sodium 4-carboxymethoxyimino-(4-HPR)
      caused a marked mitotic arrest coupled with multipolar spindle formation and
      tubulin depolymerization. To assess the compound antitumor activity, in vivo
      experiments were performed in three mouse xenograft models (ovarian and breast
      cancers and mesothelioma). The in vivo results demonstrated that retinoid
      administration as single agent significantly increased the survival in ovarian
      cancer xenografts, induced a statistically significant decrease in tumor growth
      in breast cancer xenografts, and caused a 30% reduction in tumor growth in a
      mesothelioma mouse model. Even though further studies investigating sodium 4
      carboxymethoxyimino-(4-HPR) toxicity and in vitro and in vivo activities in
      combination with other drugs are required, the double mechanism of action of the
      retinoid coupled with its in vivo antitumor efficacy and potential low toxicity
      suggest a promising therapeutic potential for the compound in different solid
      tumors.

PMID- 28491038
TI  - Yokukansan and Yokukansankachimpihange Ameliorate Aggressive Behaviors in Rats
      with Cholinergic Degeneration in the Nucleus Basalis of Meynert.
AB  - Yokukansan (YKS) and yokukansankachimpihange (YKSCH) are traditional Japanese
      Kampo medicines. The latter comprises YKS along with the medicinal herbs Citrus
      unshiu peel and Pinellia tuber. Both of these Kampo medicines are indicated for
      the treatment of night crying and irritability in children and for neurosis and
      insomnia in adults. In recent clinical trials, YKS exhibited ameliorative effects
      on the behavioral and psychological symptoms of dementia, such as aggressiveness,
      excitement, and irritability. In the present study, we aimed to clarify the
      involvement of cholinergic degeneration in the nucleus basalis of Meynert (NBM)
      in the development of aggressiveness in rats. Subsequently, using this animal
      model, the effects of YKS and YKSCH on aggressiveness were compared and the
      mechanisms underlying these effects were investigated. L-Glutamic acid (Glu) was
      injected into the right NBM of rats to induce deterioration of cholinergic
      neurons. On day 8 after Glu injection, aggressive behaviors were evaluated using
      resident-intruder tests. After the evaluation, YKS or YKSCH was administered to
      rats with aggressive behaviors daily for 7 days. In some groups, the 5-HT1A
      receptor antagonist WAY-100635 was coadministered with YKS or YKSCH over the same
      period. In other groups, locomotor activity was measured on days 12-14 after Glu
      injection. On day 15, immunohistochemistry was then performed to examine choline
      acetyltransferase (ChAT) activities in the NBM. Aggressive behaviors had
      developed on day 8 after Glu injection and were maintained until day 15. YKS and
      YKSCH significantly ameliorated the aggressive behaviors. These suppressive
      effects were entirely abolished following coadministration of WAY-100635.
      Finally, the number of ChAT-positive cells in the right NBM was significantly
      reduced on day 15 after Glu injection, and treatment with YKS or YKSCH did not
      ameliorate these reduced cell numbers. Our results show that unilateral Glu
      injections into the NBM of rats leads to the development of aggressive behaviors,
      which is thought to reflect cholinergic degeneration. YKS and YKSCH treatments
      ameliorated Glu-induced aggressive behaviors, and these effects were suggested to
      be mediated by 5-HT1A receptor stimulation, but not by improvement of cholinergic
      degeneration.

PMID- 28491039
TI  - Daily Moderate Exercise Is Beneficial and Social Stress Is Detrimental to Disease
      Pathology in Murine Lupus Nephritis.
AB  - Daily moderate exercise (DME) and stress management are underemphasized in the
      care of patients with lupus nephritis (LN) due to a poor comprehensive
      understanding of their potential roles in controlling the inflammatory response.
      To investigate these effects on murine LN, disease progression was monitored with
      either DME or social disruption stress (SDR) induction in NZM2410/J mice, which
      spontaneously develop severe, early-onset LN. SDR of previously established
      social hierarchies was performed daily for 6 days and DME consisted of treadmill
      walking (8.5 m/min for 45 min/day). SDR significantly enhanced kidney disease
      when compared to age-matched, randomly selected control counterparts, as measured
      by histopathological analysis of H&E staining and immunohistochemistry for
      complement component 3 (C3) and IgG complex deposition. Conversely, while 88% of
      non-exercised mice displayed significant renal damage by 43 weeks of age, this
      was reduced to 45% with exercise. DME also reduced histopathology in kidney
      tissue and significantly decreased deposits of C3 and IgG complexes. Further
      examination of renal infiltrates revealed a macrophage-mediated inflammatory
      response that was significantly induced with SDR and suppressed with DME, which
      also correlated with expression of inflammatory mediators. Specifically, SDR
      induced IL-6, TNF-alpha, IL-1beta, and MCP-1, while DME suppressed IL-6, TNF
      alpha, IL-10, CXCL1, and anti-dsDNA autoantibodies. These data demonstrate that
      psychological stressors and DME have significant, but opposing effects on the
      chronic inflammation associated with LN; thus identifying and characterizing
      stress reduction and a daily regimen of physical activity as potential adjunct
      therapies to complement pharmacological intervention in the management of
      autoimmune disorders, including LN.

PMID- 28491040
TI  - Association between Carotid Intima Media Thickness and Heart Rate Variability in
      Adults at Increased Cardiovascular Risk.
AB  - Background: Atherosclerotic carotid intima-media thickness (IMT) may be
      associated with alterations in the sensitivity of carotid baroreceptors. The aim
      of this study was to investigate the association between carotid IMT and the
      autonomic modulation of heart rate variability (HRV). Methods: A total of 101
      subjects were enrolled in this prospective observational study. The carotid IMT
      was determined by duplex ultrasonography. The cardiac autonomic function was
      determined through HRV measures during the Deep Breathing Test. Linear regression
      models, adjusted for demographics, comorbidities, body mass index, waist-hip
      ratio, and left ventricular ejection fraction were used to evaluate the
      association between HRV parameters and carotid IMT. Results: Participants had a
      mean age of 60.4 +/- 13.4 years and an estimated 10-year atherosclerotic
      cardiovascular disease (ASCVD) risk score (using the Pooled Cohort Equations) of
      16.4 +/- 17. The mean carotid media thickness was highest (0.90 +/- 0.19 mm) in
      the first quartile of the standard deviation of all RR intervals (SDNN) (19.7 +/-
      5.1 ms) and progressively declined in each subsequent quartile to 0.82 +/- 0.21
      mm, 0.81 +/- 0.16 mm, and 0.68 +/- 0.19 in quartiles 2 (36.5 +/- 5.9 ms), 3 (57.7
      +/- 6.2 ms) and 4 (100.9 +/- 22.2 ms), respectively. In multivariable adjusted
      models, there was a statistical significant association between SDNN and carotid
      IMT (OR -0.002; 95%CI -0.003 to -0.001, p = 0.005). The same significant
      association was found between carotid IMT and other measures of HRV, including
      coefficient of variation of RR intervals (CV) and dispersion of points along the
      line of identity (SD2). Conclusions: In a cohort of individuals at increased
      cardiovascular risk, carotid IMT as a marker of subclinical atherosclerosis was
      associated with alterations of HRV indicating an impaired cardiac autonomic
      control, independently of other cardiovascular risk factors.

PMID- 28491041
TI  - Describing the Diapause-Preparatory Proteome of the Beetle Colaphellus bowringi
      and Identifying Candidates Affecting Lipid Accumulation Using Isobaric Tags for
      Mass Spectrometry-Based Proteome Quantification (iTRAQ).
AB  - Prior to entering diapause, insects must prepare themselves physiologically to
      withstand the stresses of arresting their development for a lengthy period. While
      studies describing the biochemical and cellular milieu of the maintenance phase
      of diapause are accumulating, few studies have taken an "omics" approach to
      describing molecular events during the diapause preparatory phase. We used
      isobaric tags and mass spectrometry (iTRAQ) to quantitatively compare the
      expression profiles of proteins identified during the onset of diapause
      preparation phase in the heads of adult female cabbage beetles, Colaphellus
      bowringi. A total of 3,175 proteins were identified, 297 of which were
      differentially expressed between diapause-destined and non-diapause-destined
      female adults and could therefore be involved in diapause preparation in this
      species. Comparison of identified proteins with protein function databases shows
      that many of these differentially expressed proteins enhanced in diapause
      destined beetles are involved in energy production and conversion, carbohydrate
      metabolism and transport, and lipid metabolism. Further hand annotation of
      differentially abundant peptides nominates several associated with stress
      hardiness, including HSPs and antioxidants, as well as neural development. In
      contrast, non-diapause destined beetles show substantial increases in cuticle
      proteins, suggesting additional post-emergence growth. Using RNA interference to
      silence a fatty acid-binding protein (FABP) that was highly abundant in the head
      of diapause-destined females prevented the accumulation of lipids in the fat
      body, a common product of diapause preparation in this species and others.
      Surprisingly, RNAi against the FABP also affected the transcript abundance of
      several heat shock proteins. These results suggest that the identified
      differentially expressed proteins that play vital roles in lipid metabolism may
      also contribute somehow to enhanced hardiness to environmental stress that is
      characteristic of diapause.

PMID- 28491043
TI  - A Comparison of Children's Ability to Read Children's and Adults' Mental States
      in an Adaptation of the Reading the Mind in the Eyes Task.
AB  - The ability to read mental states from subtle facial cues is an important part of
      Theory of Mind, which can contribute to children's daily life social functioning.
      Mental state reading performance is influenced by the specific interactions in
      which it is applied; familiarity with characteristics of these interactions (such
      as the person) can enhance performance. The aim of this research is to gain
      insight in this context effect for mental state reading in children, assessed
      with the Reading the Mind in the Eyes (RME) task that originally consists of
      pictures of adults' eyes. Because of differences between children and adults in
      roles, development and frequency of interaction, children are more familiar with
      mental state reading of other children. It can therefore be expected that
      children's mental state reading depends on whether this is assessed with
      children's or adults' eyes. A new 14 item version of the RME for children was
      constructed with pictures of children instead of adults (study 1). This task was
      used and compared to the original child RME in 6-10 year olds (N = 718, study 2)
      and 8-14 year olds (N = 182, study 3). Children in both groups performed better
      on the new RME than on the original RME. Item level findings of the new RME were
      in line with previous findings on the task and test re-test reliability (in a
      subgroup of older children, n = 95) was adequate (0.47). This suggests that the
      RME with children's eyes can assess children's daily life mental state reading
      and supplement existing ToM tasks.

PMID- 28491042
TI  - Disentangling Working Memory Functioning in Mood States of Bipolar Disorder: A
      Systematic Review.
AB  - Working memory (WM) deficits are often reported in patients with Bipolar Disorder
      (BD). However, it is not clear about the nature of these WM deficits (update or
      serial order processes) and their association with each BD states (euthymic,
      mania, and depressive). This review investigated the association between BD
      patient's states and the functioning of WM components. For this purpose, we
      carried out a systematic review fulfilling a search in the databases Medline,
      Scopus, SciELO, and Web of Science using specific terms in the abstracts of the
      articles that generated 212 outcomes in the restricted period from 2005 to 2016.
      Twenty-three papers were selected, completely read, and analyzed using PICOS
      strategy. The mood episodes predicted deficits in different components of WM in
      BD patients (the phonological loop or visuospatial sketchpad) and were associated
      with different WM processes (updating and serial recall). Lower cognitive scores
      persist even in remission of symptoms. This result suggests that WM deficit
      apparently is stage-independent in BD patients. Furthermore, findings suggest
      that the neutral point on Hedonic Detector component of WM could be maladjusted
      by BD.

PMID- 28491044
TI  - Music to Make Your Mouth Water? Assessing the Potential Influence of Sour Music
      on Salivation.
AB  - People robustly associate various sound attributes with specific smells/tastes,
      and soundtracks that are associated with specific tastes can influence people's
      evaluation of the taste of food and drink. However, it is currently unknown
      whether such soundtracks directly impact the eating experience via physiological
      changes (an embodiment account), or whether they act at a higher cognitive level,
      or both. The present research assessed a version of the embodiment account, where
      a soundtrack associated with sourness is hypothesized to induce a physiological
      response in the listener by increasing salivary flow. Salivation was measured
      while participants were exposed to three different experimental conditions - a
      sour soundtrack, a muted lemon video showing a man eating a lemon, and a silent
      baseline condition. The results revealed that salivation during the lemon video
      condition was significantly greater than in the sour soundtrack and baseline
      conditions. However, contrary to our hypothesis, there was no significant
      difference between salivation levels in the sour soundtrack compared to the
      baseline condition. These results are discussed in terms of potential mechanisms
      underlying the auditory modulation of taste perception/evaluation.

PMID- 28491045
TI  - Modeling Timbre Similarity of Short Music Clips.
AB  - There is evidence from a number of recent studies that most listeners are able to
      extract information related to song identity, emotion, or genre from music
      excerpts with durations in the range of tenths of seconds. Because of these very
      short durations, timbre as a multifaceted auditory attribute appears as a
      plausible candidate for the type of features that listeners make use of when
      processing short music excerpts. However, the importance of timbre in listening
      tasks that involve short excerpts has not yet been demonstrated empirically.
      Hence, the goal of this study was to develop a method that allows to explore to
      what degree similarity judgments of short music clips can be modeled with low
      level acoustic features related to timbre. We utilized the similarity data from
      two large samples of participants: Sample I was obtained via an online survey,
      used 16 clips of 400 ms length, and contained responses of 137,339 participants.
      Sample II was collected in a lab environment, used 16 clips of 800 ms length, and
      contained responses from 648 participants. Our model used two sets of audio
      features which included commonly used timbre descriptors and the well-known Mel
      frequency cepstral coefficients as well as their temporal derivates. In order to
      predict pairwise similarities, the resulting distances between clips in terms of
      their audio features were used as predictor variables with partial least-squares
      regression. We found that a sparse selection of three to seven features from both
      descriptor sets-mainly encoding the coarse shape of the spectrum as well as
      spectrotemporal variability-best predicted similarities across the two sets of
      sounds. Notably, the inclusion of non-acoustic predictors of musical genre and
      record release date allowed much better generalization performance and explained
      up to 50% of shared variance (R2) between observations and model predictions.
      Overall, the results of this study empirically demonstrate that both acoustic
      features related to timbre as well as higher level categorical features such as
      musical genre play a major role in the perception of short music clips.

PMID- 28491046
TI  - 'The More We Stand For - The More We Fight For': Compatibility and Legitimacy in
      the Effects of Multiple Social Identities.
AB  - This paper explores the expression of multiple social identities through
      coordinated collective action. We propose that perceived compatibility between
      potentially contrasting identities and perceived legitimacy of protest serve as
      catalysts for collective action. The present paper maps the context of the
      "Euromaidan" anti-regime protests in Ukraine and reports data (N = 996) collected
      through an online survey following legislation to ban protests (March-May, 2014).
      We measured participants' identification with three different groups (the
      Ukrainian nation, the online protest community, and the street movement),
      perception of compatibility between online protest and the street movement,
      perception of the legitimacy of protest, and intentions to take persuasive and
      confrontational collective action. We found evidence that the more social groups
      people "stood for," the more they "fought" for their cause and that
      identifications predicted both forms of collective action to the degree that
      people saw the protest and the online movement as compatible with each other and
      believed protest to be legitimate. Collective action can be interpreted as the
      congruent expression of multiple identities that are rendered ideologically
      compatible both in online settings and on the street.

PMID- 28491047
TI  - Upper Limb Asymmetry in the Sense of Effort Is Dependent on Force Level.
AB  - Previous studies have shown that asymmetries in upper limb sensorimotor function
      are dependent on the source of sensory and motor information, hand preference and
      differences in hand strength. Further, the utilization of sensory and motor
      information and the mode of control of force may differ between the right
      hand/left hemisphere and left hand/right hemisphere systems. To more clearly
      understand the unique contribution of hand strength and intrinsic differences to
      the control of grasp force, we investigated hand/hemisphere differences when the
      source of force information was encoded at two different force levels
      corresponding to a 20 and 70% maximum voluntary contraction or the right and left
      hand of each participant. Eleven, adult males who demonstrated a stronger right
      than left maximum grasp force were requested to match a right or left hand 20 or
      70% maximal voluntary contraction reference force with the opposite hand. During
      the matching task, visual feedback corresponding to the production of the
      reference force was available and then removed when the contralateral hand
      performed the match. The matching relative force error was significantly
      different between hands for the 70% MVC reference force but not for the 20% MVC
      reference force. Directional asymmetries, quantified as the matching force
      constant error, showed right hand overshoots and left undershoots were force
      dependent and primarily due to greater undershoots when matching with the left
      hand the right hand reference force. Findings further suggest that the
      interaction between internal sources of information, such as efferent copy and
      proprioception, as well as hand strength differences appear to be hand/hemisphere
      system dependent. Investigations of force matching tasks under conditions whereby
      force level is varied and visual feedback of the reference force is available
      provides critical baseline information for building effective interventions for
      asymmetric (stroke-related, Parkinson's Disease) and symmetric (Amyotrophic
      Lateral Sclerosis) upper limb recovery of neurological conditions where the
      various sources of sensory - motor information have been significantly altered by
      the disease process.

PMID- 28491048
TI  - Both the "What" and "Why" of Youth Sports Participation Matter; a Conditional
      Process Analysis.
AB  - This study builds on previous research combining achievement goal orientation
      from Achievement Goal Theory and motivational regulation from Self-Determination
      Theory. The aim was to assess the combination of the "what" and "why" of youth
      sport activity, and how it relates to the need for competence and self-esteem.
      Achievement goal orientation, specifically task and ego, was employed to
      represent the "what", whilst intrinsic and external regulation reflected the
      "why". Based on a sample of 496 youth sports participants, structural equation
      modeling with a bootstrapping procedure was used to examine whether the indirect
      relationship between achievement goal orientation and self-esteem was conditional
      to motivational regulation. The results show partial support for the conditional
      process models. Specifically, task orientation was indirectly linked with self
      esteem through competence need, and the relationship was stronger with higher
      levels of intrinsic regulation for sport. Furthermore, ego orientation was
      negatively associated with self-esteem through a positive relationship with
      competence frustration. However, this relationship emerged only for those higher
      in intrinsic regulation. External regulation did not emerge as a moderator, but
      presented a positive relationship with competence frustration. Findings are
      discussed in light of both Achievement Goal Theory and Self-Determination Theory,
      and underline the importance of considering both the "what" and "why" when
      attempting to understand motivation in youth sport.

PMID- 28491049
TI  - Sleep Disturbances in Phenylketonuria: An Explorative Study in Men and Mice.
AB  - Sleep problems have not been directly reported in phenylketonuria (PKU). In PKU,
      the metabolic pathway of phenylalanine is disrupted, which, among others, causes
      deficits in the neurotransmitters and sleep modulators dopamine, norepinephrine,
      and serotonin. Understanding sleep problems in PKU patients may help explain the
      pathophysiology of brain dysfunction in PKU patients. In this explorative study,
      we investigated possible sleep problems in adult treated PKU patients and
      untreated PKU mice. In the PKU patients, sleep characteristics were compared to
      healthy first degree relatives by assessment of sleep disturbances, sleep-wake
      patterns, and sleepiness with the help of four questionnaires: Holland sleep
      disorder questionnaire, Pittsburgh sleep quality index, Epworth sleepiness scale,
      and Munich Chronotype Questionnaire. The results obtained with the questionnaires
      show that PKU individuals suffer more from sleep disorders, a reduced sleep
      quality, and an increased latency to fall asleep and experience more sleepiness
      during the day. In the PKU mice, activity patterns were recorded with passive
      infrared recorders. PKU mice switched more often between active and non-active
      behavior and shifted a part of their resting behavior into the active period,
      confirming that sleep quality is affected as a consequence of PKU. Together,
      these results give the first indication that sleep problems are present in PKU.
      More detailed future research will give a better understanding of these problems,
      which could ultimately result in the improvement of treatment strategies by
      including sleep quality as an additional treatment target.

PMID- 28491050
TI  - A Persistent Primitive Hypoglossal Artery As the Sole Supply to the Brain
      Associated with a Basilar Bifurcation Aneurysm.
AB  - The persistent primitive hypoglossal artery (PPHA) is the second most common
      persistent carotid-vertebrobasilar anastomosis, with an incidence of 0.027-0.26%.
      PPHAs change the hemodynamics of the carotid and vertebrobasilar system and may
      be associated with intracranial vascular anomalies, but basilar bifurcation
      aneurysms were rarely reported. We describe the first case of a PPHA as the sole
      supply to the brain associated with a basilar bifurcation aneurysm and review the
      literature. We reported a 34-year-old woman who presented with subarachnoid
      hemorrhage due to a ruptured basilar bifurcation aneurysm. Digital subtraction
      arteriogram revealed a right PPHA as the sole supply to the brain. The aneurysm
      was successfully clipped under intraoperative neurophysiology.

PMID- 28491051
TI  - Hashimoto's Thyroiditis and Autoimmune Gastritis.
AB  - The term "thyrogastric syndrome" defines the association between autoimmune
      thyroid disease and chronic autoimmune gastritis (CAG), and it was first
      described in the early 1960s. More recently, this association has been included
      in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis
      represents the pivotal disorder. Hashimoto's thyroiditis (HT) is the most
      frequent autoimmune disease, and it has been reported to be associated with
      gastric disorders in 10-40% of patients while about 40% of patients with
      autoimmune gastritis also present HT. Some intriguing similarities have been
      described about the pathogenic mechanism of these two disorders, involving a
      complex interaction among genetic, embryological, immunologic, and environmental
      factors. CAG is characterized by a partial or total disappearance of parietal
      cells implying the impairment of both hydrochloric acid and intrinsic factor
      production. The clinical outcome of this gastric damage is the occurrence of a
      hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia
      concomitant with the progression to a severe gastric atrophy. Malabsorption of
      levothyroxine may occur as well. We have briefly summarized in this minireview
      the most recent achievements on this peculiar association of diseases that, in
      the last years, have been increasingly diagnosed.

PMID- 28491052
TI  - Receptor-Mediated Melanoma Targeting with Radiolabeled alpha-Melanocyte
      Stimulating Hormone: Relevance of the Net Charge of the Ligand.
AB  - A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1
      receptors (MC1Rs) for alpha-melanocyte-stimulating hormone. Radiolabeled linear
      or cyclic analogs of alpha-MSH have a great potential as diagnostic or
      therapeutic tools for the management of malignant melanoma. Compounds such as
      [111In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor
      uptake in vivo, but they may suffer from relatively high kidney uptake and
      retention in vivo. We have shown previously that the introduction of negative
      charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their
      excretion and reduce kidney retention. To address the question of where to place
      negative charges within the ligand, we have extended these studies by designing
      two novel peptides, Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys(DOTA)-d-Asp-d-Asp-OH
      (DOTA-NAP-d-Asp-d-Asp) with three negative charges at the C-terminal end (overall
      net charge of the molecule -2) and DOTA-Gly-Tyr(P)-Nle-Asp-His-d-Phe-Arg-Trp-NH2
      (DOTA-Phospho-MSH2-9) with two negative charges in the N-terminal region (net
      charge -1). The former peptide showed markedly reduced receptor affinity and
      biological activity by >10-fold compared to DOTA-NAP-amide as reference compound,
      and the latter peptide displayed similar bioactivity and receptor affinity as the
      reference compound. The uptake by melanoma tumor tissue of [111In]DOTA-Phospho
      MSH2-9 was 7.33 +/- 0.47 %ID/g 4 h after injection, i.e., almost equally high as
      with [111In]DOTA-NAP-amide. The kidney retention was 2.68 +/- 0.18 %ID/g 4 h
      after injection and hence 44% lower than that of [111In]DOTA-NAP-amide. Over an
      observation period from 4 to 48 h, the tumor-to-kidney ratio of [111In]DOTA
      Phospho-MSH2-9 was 35% more favorable than that of the reference compound. In a
      comparison of DOTA-NAP-d-Asp-d-Asp, DOTA-Phospho-MSH2-9 and DOTA-NAP-amide with
      five previously published analogs of DOTA-NAP-amide that altogether cover a range
      of peptides with an overall net charge between +2 and -2, we now demonstrate that
      a net charge of -1, with the extra negative charges preferably placed in the N
      terminal region, has led to the lowest kidney uptake and retention. Charges of +2
      or -2 markedly increased kidney uptake and retention. In conclusion, the novel
      DOTA-Phospho-MSH2-9 may represent a new lead compound for negatively charged
      linear MC1R ligands that can be further developed into a clinically relevant
      melanoma targeting radiopeptide.

PMID- 28491053
TI  - Hydrophobicity of Residue 128 of the Stress-Inducible Sigma Factor RpoS Is
      Critical for Its Activity.
AB  - RpoS is a key stress-inducible sigma factor that regulates stress resistance
      genes in Escherichia coli, such as the katE gene encoding catalase HPII and the
      glg genes encoding glycogen synthesis proteins. Monitoring RpoS activity can
      provide information on the stress sensitivity of E. coli isolates in clinical
      settings because the RpoS in these isolates is often mutated. In the present
      study, we found a novel, missense point mutation at RpoS residue 128 in a
      clinical Shiga toxin-producing E. coli (STEC) isolate. This mutation caused RpoS
      dysfunction and increased stress sensitivity. A mutant rpoS was cloned from a
      clinical STEC that is vulnerable to cold temperature and oxidative stresses.
      Mutant RpoS protein expression was detected in the clinical isolate, and this
      RpoS was non-functional according to HPII activity and glycogen levels, which are
      positively regulated by RpoS and thus are used as indicators for RpoS function. A
      reporter assay with beta-galactosidase indicated that the dysfunction occurred at
      the transcriptional level of genes regulated by RpoS. Furthermore, substitution
      analysis indicated that the hydrophobicity of the amino acid at residue 128 was
      critical for RpoS activity; the simulation analysis indicated that the amino
      acids of RNA polymerase (RNAP) that interact with RpoS residue 128 are
      hydrophobic, suggesting that this hydrophobic interaction is critical for RpoS
      activity. In addition, substitution of Ile128 to Pro128 abolished RpoS activity,
      possibly as a result of disruption of the secondsary structure around residue
      128, indicating that the structure is also a crucial factor for RpoS activity.
      These results indicate that only one point mutation at a hydrophobic residue of
      the complex formed during transcription leads to a critical change in RpoS
      regulation. Moreover, we found that Ile128 is widely conserved among various
      bacteria: several bacterial strains have Met128 or Leu128, which are hydrophobic
      residues, and these strains had similar or higher RpoS activity than that
      observed with Ile128 in this study. These data indicate that the hydrophobicity
      of the amino acid at residue 128 is critical for RpoS activity and is
      consequently important for bacterial survival. Taken together, these findings may
      contribute to a deeper understanding of protein functional mechanisms and
      bacterial stress responses.

PMID- 28491054
TI  - Flexible Carbon-Use Efficiency across Litter Types and during Decomposition
      Partly Compensates Nutrient Imbalances-Results from Analytical Stoichiometric
      Models.
AB  - Mathematical models involving explicit representations of microbial processes
      have been developed to infer microbial community properties from laboratory and
      field measurements. While this approach has been used to estimate the kinetic
      constants related to microbial activity, it has not been fully exploited for
      inference of stoichiometric traits, such as carbon-use efficiency (CUE). Here, a
      hierarchy of analytically-solvable mass-balance models of litter carbon (C) and
      nitrogen (N) dynamics is developed, to infer decomposer CUE from measured C and N
      contents during litter decomposition. The models are solved in the phase space
      expressing litter remaining N as a function of remaining C-rather than in time,
      thus focusing on the stoichiometric relations during decomposition rather than
      the kinetics of degradation. This approach leads to explicit formulas that depend
      on CUE and other microbial properties, which can then be treated as model
      parameters and retrieved via nonlinear regression. CUE is either assumed time
      invariant or as a function of the fraction of remaining litter C as a substitute
      for time. In all models, CUE tends to increase with increasing litter N
      availability across a range of litter types. When temporal trends in CUE are
      considered, CUE increases during decomposition of N-poor litter cohorts, in which
      decomposers are initially N-limited, but decreases in N-rich litter possibly due
      to C-limitation. These patterns of flexible CUE that partly compensate
      stoichiometric imbalances are robust to moderate shifts in decomposer C:N ratio
      and hold across wide climatic gradients.

PMID- 28491055
TI  - Metagenomic Sequencing of Diamondback Moth Gut Microbiome Unveils Key Holobiont
      Adaptations for Herbivory.
AB  - Herbivore specialists adapt to feed on a specific group of host plants by
      evolving various mechanisms to respond to plant defenses. Insects also possess
      complex gut microbiotas but their potential role in adaptation is poorly
      understood. Our previous study of the genome of diamondback moth, Plutella
      xylostella, revealed an intrinsic capacity to detoxify plant defense compounds,
      which is an important factor in its success as a pest. Here we expand on that
      work with a complete taxonomic and functional profile of the P. xylostella gut
      microbiota obtained by metagenomic sequencing. Gene enrichment in the metagenome,
      accompanied by functional identification, revealed an important role of specific
      gut bacteria in the breakdown of plant cell walls, detoxification of plant
      phenolics, and synthesis of amino acids. Microbes participating in these pathways
      mainly belonged to three highly abundant bacteria: Enterobacter cloacae,
      Enterobacter asburiae, and Carnobacterium maltaromaticum. Results show that while
      the gut microbial community may be complex, a small number of functionally active
      species can be disproportionally important. The presence of specific enzymes in
      the microbiota community, such as supporting amino acid synthesis, digestion and
      detoxification functions, demonstrates the beneficial interactions between P.
      xylostella and its gut microbiota. These interactions can be potential targets
      for manipulation to provide novel pest management approaches.

PMID- 28491056
TI  - Prochlorococcus as a Possible Source for Transparent Exopolymer Particles (TEP).
AB  - Transparent exopolymer particles (TEP), usually associated with phytoplankton
      blooms, promote the formation of marine aggregates. Their exportation to deep
      waters is considered a key component of the biological carbon pump. Here, we
      explored the role of solar radiation and picocyanobacteria in the formation of
      TEP in oligotrophic surface waters of the Atlantic and Pacific Oceans in ten on
      deck incubation experiments during the Malaspina 2010 Expedition. TEP
      concentrations were low on the ocean's surface although these concentrations were
      significantly higher on the surface of the Pacific (24.45 +/- 2.3 MUg XG Eq. L-1)
      than on the surface of the Atlantic Ocean (8.18 +/- 4.56 MUg XG Eq. L-1). Solar
      radiation induced a significant production of TEP in the on-deck experiments from
      the surface water of the Pacific Ocean, reaching values up to 187.3 MUg XG Eq. L
      1 compared with the low production observed in the dark controls. By contrast,
      TEP production in the Atlantic Ocean experiments was lower, and its formation was
      not related to the light treatments. Prochlorococcus sp. from the surface ocean
      was very sensitive to solar radiation and experienced a high cell decay in the
      Pacific Ocean experiments. TEP production in the on-deck incubation experiments
      was closely related to the observed cell decay rates of Prochlorococcus sp.,
      suggesting that this picocyanobacteria genus is a potential source of TEP. The
      evidence to propose such potential role was derived experimentally, using natural
      communities including the presence of several species and a variety of processes.
      Laboratory experiments with cultures of a non-axenic strain of Prochlorococcus
      marinus were then used to test TEP production by this genus. TEP concentrations
      in the culture increased with increasing cell abundance during the exponential
      phase, reaching the highest TEP concentration at the beginning of the stationary
      phase. The average TEP concentration of 1474 +/- 226 MUg XG Eq. L-1 (mean +/- SE)
      observed at the stationary phase of P. marinus cultures is comparable with the
      values reported in the literature for diatom cultures, also growing in non-axenic
      as well as axenic cultures. Our results identify Prochlorococcus sp. as a
      possible relevant source of TEP in the oligotrophic ocean.

PMID- 28491057
TI  - Identification of Genes Controlled by the Essential YycFG Two-Component System
      Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis.
AB  - Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis,
      while little is known about whether the essential YycFG two-component signal
      transduction system (TCS) is involved in biofilm formation. We used antisense RNA
      (asRNA) to silence the yycFG TCS in order to study its regulatory functions in S.
      epidermidis. Strain 1457 expressing asRNA yycF exhibited a significant delay (~4
      5 h) in entry to log phase, which was partially complemented by overexpressing
      ssaA. The expression of asRNA yycF and asRNA yycG resulted in a 68 and 50%
      decrease in biofilm formation at 6 h, respectively, while they had no significant
      inhibitory effect on 12 h biofilm formation. The expression of asRNA yycF led to
      a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but
      it did not affect the expression of accumulation-associated protein (Aap) or the
      release of extracellular DNA. Consistently, quantitative real-time PCR showed
      that silencing yycF resulted in an increased transcription of biofilm-related
      genes, including icaA, arlR, sarA, sarX, and sbp. An in silico search of the YycF
      regulon for the conserved YycF recognition pattern and a modified motif in S.
      epidermidis, along with additional gel shift and DNase I footprinting assays,
      showed that arlR, sarA, sarX, and icaA are directly regulated by YycF. Our data
      suggests that YycFG modulates S. epidermidis biofilm formation in an ica
      dependent manner.

PMID- 28491058
TI  - A Meta-Transcriptomics Survey Reveals Changes in the Microbiota of the Chinese
      Mitten Crab Eriocheir sinensis Infected with Hepatopancreatic Necrosis Disease.
AB  - Infection of the freshwater Chinese mitten crab Eriocheir sinensis with
      hepatopancreatic necrosis disease (HPND) has been a major problem in the crab
      cultivated Chinese Province of Jiangsu since 2015. To explore the etiology of
      HPND, meta-transcriptomic libraries of the hepatopancreata from crabs with and
      without HPND were constructed. Comparison analyses showed that there were no
      statistically significant differences in viral and microsporidial communities in
      the hepatopancreata of diseased and healthy crabs. Bacteroidetes, Proteobacteria,
      and Firmicutes were the most dominant bacterial phyla in the hepatopancreata of
      healthy crabs, with a combined prevalence of 93%. However, a decrease in
      bacterial diversity and a striking shift in the microbial composition were found
      in the hepatopancreata of crabs infected with HPND. Tenericutes was the most
      prevalent bacterial phylum in diseased crabs (31.82%), whereas its prevalence was
      low in healthy crabs (0.02%). By contrast, the prevalence of Bacteroidetes was
      significantly lower in crabs with HPND (3.49%) than in crabs without HPND
      (41.04%). We also found that the prevalence of Actinobacteria was higher in crabs
      with HPND (16.70%) than in crabs without the disease (4.03%). The major bacterial
      family within the Tenericutes phylum in crabs with HPND was detected by
      polymerase chain reaction and determined to be Mycoplasmataceae. In conclusion,
      there were striking changes in the microbiota of diseased and healthy crabs.
      Specifically, the prevalence of bacteria belonging to Tenericutes and
      Actinobacteria phyla increased, whereas the prevalence of bacteria belonging to
      the Bacteroidetes phylum decreased in crabs with HPND, clearly pointing to an
      association with HPND.

PMID- 28491059
TI  - Elucidation of the Role of 3-Hydroxy Fatty Acids in Cryptococcus-amoeba
      Interactions.
AB  - We previously reported that 3-hydroxy fatty acids promoted the survival of
      cryptococcal cells when acted upon by amoebae. To expand on this, the current
      study sought to explain how these molecules may protect cells. Our data suggest
      that 3-hydroxy fatty acids may subvert the internalization of cryptococcal cells
      via suppression of the levels of a fetuin A-like amoebal protein, which may be
      important for enhancing phagocytosis. Additionally, we show that an acapsular
      strain (that is devoid of 3-hydroxy fatty acids) was protected against the
      effects of hydrogen peroxide when exogenous 3-hydroxy fatty acids were present,
      but not in the absence of 3-hydroxy fatty acids. A similar response profile was
      noted when a strain with a capsule was challenged with hydrogen peroxide. We also
      show that cryptococcal cells that naturally produce 3-hydroxy fatty acids were
      more resistant to the effects of amoebapore (an amoeba-specific hydrolytic
      enzyme), compared to cells that do not produce these molecules. Taken together,
      our findings suggest that 3-hydroxy fatty acids possess an anti-phagocytic
      activity that may be expressed when cells interact with macrophages. This may
      allow the yeast cells to evade immuno-processing.

PMID- 28491061
TI  - 4,4'-Diaponeurosporene-Producing Bacillus subtilis Increased Mouse Resistance
      against Salmonella typhimurium Infection in a CD36-Dependent Manner.
AB  - Deficient mucosal innate immunity is a hallmark of infectious diarrhea, such as
      Salmonella typhimurium (S. typhimurium)-induced gastroenteritis. Here, we report
      that oral administration of a 4,4'-diaponeurosporene-producing Bacillus subtilis
      (B.s-Dia) could improve mice mucosal immunity, as showed by an increased
      resistance against S. typhimurium infection. Intragastric administration of B.s
      Dia for 7 days could increase the secretion of CCL20 by intestinal epithelial
      cells (IECs) and then recruit more dendritic cells. Meanwhile, the number of
      CD8alphaalpha+ intraepithelial lymphocytes, which play a critical role in
      downregulating immune responses, was also reduced, probably as a consequence of
      the decrease of IEC-derived TGFbeta. Further study showed that CD36 played a
      critical role in B.s-Dia-induced immune enhancement, as blocking CD36 signal with
      a specific antagonist, sulfo-N-succinimidyl oleate, led to the inability of B.s
      Dia to enhance mucosal innate immunity.

PMID- 28491060
TI  - Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation.
AB  - Natural killer (NK) cells are a promising tool for the use in adoptive
      immunotherapy, since they efficiently recognize and kill tumor cells. In this
      context, ex vivo cultivation is an attractive option to increase NK cells in
      numbers and to improve their antitumor potential prior to clinical applications.
      Consequently, various strategies to generate NK cells for adoptive immunotherapy
      have been developed. Here, we give an overview of different NK cell cultivation
      approaches and their impact on shaping the NK cell antitumor activity. So far,
      the cytokines interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 are used to
      culture and expand NK cells. The selection of the respective cytokine combination
      is an important factor that directly affects NK cell maturation, proliferation,
      survival, distribution of NK cell subpopulations, activation, and function in
      terms of cytokine production and cytotoxic potential. Importantly, cytokines can
      upregulate the expression of certain activating receptors on NK cells, thereby
      increasing their responsiveness against tumor cells that express the
      corresponding ligands. Apart from using cytokines, cocultivation with autologous
      accessory non-NK cells or addition of growth-inactivated feeder cells are
      approaches for NK cell cultivation with pronounced effects on NK cell activation
      and expansion. Furthermore, ex vivo cultivation was reported to prime NK cells
      for the killing of tumor cells that were previously resistant to NK cell attack.
      In general, NK cells become frequently dysfunctional in cancer patients, for
      instance, by downregulation of NK cell activating receptors, disabling them in
      their antitumor response. In such scenario, ex vivo cultivation can be helpful to
      arm NK cells with enhanced antitumor properties to overcome immunosuppression. In
      this review, we summarize the current knowledge on NK cell modulation by
      different ex vivo cultivation strategies focused on increasing NK cytotoxicity
      for clinical application in malignant diseases. Moreover, we critically discuss
      the technical and regulatory aspects and challenges underlying NK cell based
      therapeutic approaches in the clinics.

PMID- 28491062
TI  - A Kinetic Study of CD83 Reveals an Upregulation and Higher Production of sCD83 in
      Lymphocytes from Pregnant Mice.
AB  - For the normal development of pregnancy, a balance between immune tolerance and
      defense is crucial. However, the mechanisms mediating such a balance are not
      fully understood. CD83 is a transmembrane protein whose expression has been
      linked to anti-inflammatory functions of T and B cells. The soluble form of CD83,
      released by cleavage of the membrane-bound protein, has strong anti-inflammatory
      properties and was successfully tested in different mouse models. It is assumed
      that this molecule contributes to the establishment of immune tolerance.
      Therefore, we postulated that the expression of CD83 is crucial for immune
      tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound
      form of CD83 was upregulated in T and B cells during allogeneic murine
      pregnancies. An upregulation was also evident in the main splenic B cell
      subtypes: marginal zone, follicular zone, and transitional B cells. We also
      showed that there was an augmentation in the number of CD83+ cells toward the end
      of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were
      reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B
      lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in
      terms of CD83 expression and sCD83 release. Progesterone induced a dosis
      dependent upregulation of CD83 on T cells. Our data suggest that the regulation
      of CD83 expression represents a novel pathway of fetal tolerance and protection
      against inflammatory threats during pregnancy.

PMID- 28491063
TI  - ISA-2011B, a Phosphatidylinositol 4-Phosphate 5-Kinase alpha Inhibitor, Impairs
      CD28-Dependent Costimulatory and Pro-inflammatory Signals in Human T Lymphocytes.
AB  - Phosphatidylinositol 4,5-biphosphate (PIP2) is a membrane phospholipid that
      controls the activity of several proteins regulating cytoskeleton reorganization,
      cytokine gene expression, T cell survival, proliferation, and differentiation.
      Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) are the main enzymes involved
      in PIP2 biosynthesis by phosphorylating phosphatidylinositol 4-monophosphate
      (PI4P) at the D5 position of the inositol ring. In human T lymphocytes, we
      recently found that CD28 costimulatory molecule is pivotal for PIP2 turnover by
      recruiting and activating PIP5Kalpha. We also found that PIP5Kalpha is the main
      regulator of both CD28 costimulatory signals integrating those delivered by TCR
      as well as CD28 autonomous signals regulating the expression of pro-inflammatory
      genes. Given emerging studies linking alterations of PIP2 metabolism to immune
      based diseases, PIP5Kalpha may represent a promising target to modulate immunity
      and inflammation. Herewith, we characterized a recently discovered inhibitor of
      PIP5Kalpha, ISA-2011B, for its inhibitory effects on T lymphocyte functions. We
      found that the inhibition of PIP5Kalpha lipid-kinase activity by ISA-2011B
      significantly impaired CD28 costimulatory signals necessary for TCR-mediated Ca2+
      influx, NF-AT transcriptional activity, and IL-2 gene expression as well as CD28
      autonomous signals regulating the activation of NF-kappaB and the transcription
      of pro-inflammatory cytokine and chemokine genes. Moreover, our data on the
      inhibitory effects of ISA-2011B on CD28-mediated upregulation of inflammatory
      cytokines related to Th17 cell phenotype in type 1 diabetes patients suggest ISA
      2011B as a promising anti-inflammatory drug.

PMID- 28491065
TI  - OsPhyB-Mediating Novel Regulatory Pathway for Drought Tolerance in Rice Root
      Identified by a Global RNA-Seq Transcriptome Analysis of Rice Genes in Response
      to Water Deficiencies.
AB  - Water deficiencies are one of the most serious challenges to crop productivity.
      To improve our understanding of soil moisture stress, we performed RNA-Seq
      analysis using roots from 4-week-old rice seedlings grown in soil that had been
      subjected to drought conditions for 2-3 d. In all, 1,098 genes were up-regulated
      in response to soil moisture stress for 3 d, which causes severe damage in root
      development after recovery, unlikely that of 2 d. Comparison with previous
      transcriptome data produced in drought condition indicated that more than 68% of
      our candidate genes were not previously identified, emphasizing the novelty of
      our transcriptome analysis for drought response in soil condition. We then
      validated the expression patterns of two candidate genes using a promoter-GUS
      reporter system in planta and monitored the stress response with novel molecular
      markers. An integrating omics tool, MapMan analysis, indicated that RING box E3
      ligases in the ubiquitin-proteasome pathways are significantly stimulated by
      induced drought. We also analyzed the functions of 66 candidate genes that have
      been functionally investigated previously, suggesting the primary roles of our
      candidate genes in resistance or tolerance relating traits including drought
      tolerance (29 genes) through literature searches besides diverse regulatory roles
      of our candidate genes for morphological traits (15 genes) or physiological
      traits (22 genes). Of these, we used a T-DNA insertional mutant of rice
      phytochrome B (OsPhyB) that negatively regulates a plant's degree of tolerance to
      water deficiencies through the control of total leaf area and stomatal density
      based on previous finding. Unlike previous result, we found that OsPhyB represses
      the activity of ascorbate peroxidase and catalase mediating reactive oxygen
      species (ROS) processing machinery required for drought tolerance of roots in
      soil condition, suggesting the potential significance of remaining
      uncharacterized candidate genes for manipulating drought tolerance in rice.

PMID- 28491066
TI  - Robust Phylogeny of Tetrastigma (Vitaceae) Based on Ten Plastid DNA Regions:
      Implications for Infrageneric Classification and Seed Character Evolution.
AB  - Tetrastigma (Miq.) Planch. is one of the most species-rich genera of the
      economically and agronomically important grape family Vitaceae. It includes ca.
      95 species widely distributed in the tropics and subtropics of Asia and
      Australia. Species of Tetrastigma exhibit great diversity in both vegetative and
      reproductive characters. Here we inferred a well-supported phylogeny of
      Tetrastigma based on ten chloroplast DNA regions with an expanded taxon sampling
      of 72 species and two varieties. Our molecular results support six major clades
      within Tetrastigma and the relationships among these clades were well-resolved.
      We also documented seed morphology of 44 species covering the six major clades of
      the genus. Ancestral states of eight characters (seed shape, seed surface
      rumination pattern, chalaza length/width ratio, chalaza position, ventral infold
      position, ventral infold divergence, ventral infold depth in cross section, and
      endosperm shape) were reconstructed in Mesquite and R with four models. Character
      optimizations suggest that all character states have evolved multiple times
      except that the irregular-shaped surface rumination has derived only once in
      Tetrastigma. We evaluated the taxonomic importance of seed morphology and
      identified potential morphological evidence to support each major clade. Our
      comprehensive analyses of Tetrastigma shed insights into the infrageneric
      classification of this morphologically diverse and ecologically important genus
      in tropical and subtropical Asia.

PMID- 28491064
TI  - Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration.
AB  - Inflammation is increasingly implicated in neurodegenerative disease pathology.
      As no acquired pathogen appears to drive this inflammation, the question of what
      does remains. Recent advances indicate damage-associated molecular pattern (DAMP)
      molecules, which are released by injured and dying cells, can cause specific
      inflammatory cascades. Inflammation, therefore, can be endogenously induced.
      Mitochondrial components induce inflammatory responses in several pathological
      conditions. Due to evidence such as this, a number of mitochondrial components,
      including mitochondrial DNA, have been labeled as DAMP molecules. In this review,
      we consider the contributions of mitochondrial-derived DAMPs to inflammation
      observed in neurodegenerative diseases.

PMID- 28491067
TI  - Genome-Wide Association Study Reveals the Genetic Architecture Underlying Salt
      Tolerance-Related Traits in Rapeseed (Brassica napus L.).
AB  - Soil salinity is a serious threat to agriculture sustainability worldwide. Salt
      tolerance at the seedling stage is crucial for plant establishment and high yield
      in saline soils; however, little information is available on rapeseed (Brassica
      napus L.) salt tolerance. We evaluated salt tolerance in different rapeseed
      accessions and conducted a genome-wide association study (GWAS) to identify salt
      tolerance-related quantitative trait loci (QTL). A natural population comprising
      368 B. napus cultivars and inbred lines was genotyped with a Brassica 60K
      Illumina Infinium SNP array. The results revealed that 75 single-nucleotide
      polymorphisms (SNPs) distributed across 14 chromosomes were associated with four
      salt tolerance-related traits. These SNPs integrated into 25 QTLs that explained
      4.21-9.23% of the phenotypic variation in the cultivars. Additionally, 38
      possible candidate genes were identified in genomic regions associated with salt
      tolerance indices. These genes fell into several functional groups that are
      associated with plant salt tolerance, including transcription factors,
      aquaporins, transporters, and enzymes. Thus, salt tolerance in rapeseed involves
      complex molecular mechanisms. Our results provide valuable information for
      studying the genetic control of salt tolerance in B. napus seedlings and may
      facilitate marker-based breeding for rapeseed salt tolerance.

PMID- 28491068
TI  - Phytoplasmas-The "Crouching Tiger" Threat of Australian Plant Pathology.
AB  - Phytoplasmas are insect-vectored bacteria that cause disease in a wide range of
      plant species. The increasing availability of molecular DNA analyses, expertise
      and additional methods in recent years has led to a proliferation of discoveries
      of phytoplasma-plant host associations and in the numbers of taxonomic groupings
      for phytoplasmas. The widespread use of common names based on the diseases with
      which they are associated, as well as separate phenetic and taxonomic systems for
      classifying phytoplasmas based on variation at the 16S rRNA-encoding gene,
      complicates interpretation of the literature. We explore this issue and related
      trends through a focus on Australian pathosystems, providing the first
      comprehensive compilation of information for this continent, covering the
      phytoplasmas, host plants, vectors and diseases. Of the 33 16Sr groups reported
      internationally, only groups I, II, III, X, XI and XII have been recorded in
      Australia and this highlights the need for ongoing biosecurity measures to
      prevent the introduction of additional pathogen groups. Many of the phytoplasmas
      reported in Australia have not been sufficiently well studied to assign them to
      16Sr groups so it is likely that unrecognized groups and sub-groups are present.
      Wide host plant ranges are apparent among well studied phytoplasmas, with
      multiple crop and non-crop species infected by some. Disease management is
      further complicated by the fact that putative vectors have been identified for
      few phytoplasmas, especially in Australia. Despite rapid progress in recent years
      using molecular approaches, phytoplasmas remain the least well studied group of
      plant pathogens, making them a "crouching tiger" disease threat.

PMID- 28491069
TI  - Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae.
AB  - Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals
      by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the
      activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG
      proteins were extensively studied in higher plants, but their function and target
      genes in unicellular branches of the green lineage remain largely unknown. To
      shed light on PcG function and modus operandi in a broad evolutionary context, we
      demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3
      biochemical presence in several unicellular algae of different phylogenetic
      subclades. We focus then on one of the species, the model red alga
      Cyanidioschizon merolae, and show that H3K27me3 occupies both, genes and
      repetitive elements, and mediates the strength of repression depending on the
      differential occupancy over gene bodies. Furthermore, we report that H3K27me3 in
      C. merolae is enriched in telomeric and subtelomeric regions of the chromosomes
      and has unique preferential binding toward intein-containing genes involved in
      protein splicing. Thus, our study gives important insight for Polycomb-mediated
      repression in lower eukaryotes, uncovering a previously unknown link between
      H3K27me3 targets and protein splicing.

PMID- 28491071
TI  - Exploring Blueberry Aroma Complexity by Chromatographic and Direct-Injection
      Spectrometric Techniques.
AB  - Blueberry (Vaccinium spp.) fruit consumption has increased over the last 5 years,
      becoming the second most important soft fruit species after strawberry. Despite
      the possible economic and sensory impact, the blueberry volatile organic compound
      (VOC) composition has been poorly investigated. Thus, the great impact of the
      aroma on fruit marketability stimulates the need to step forward in the
      understanding of this quality trait. Beside the strong effect of ripening,
      blueberry aroma profile also varies due to the broad genetic differences among
      Vaccinium species that have been differently introgressed in modern commercial
      cultivars through breeding activity. In the present study, divided into two
      different activities, the complexity of blueberry aroma was explored by an
      exhaustive untargeted VOC analysis, performed by two complementary methods: SPME
      GC-MS (solid phase microextraction- gas chromatography-mass spectrometry) and PTR
      ToF-MS (proton transfer reaction-time of flight-mass spectrometry). The first
      experiment was aimed at determining the VOC modifications during blueberry
      ripening for five commercially representative cultivars ("Biloxi," "Brigitta
      Blue," "Centurion," "Chandler," and "Ozark Blue") harvested at four ripening
      stages (green, pink, ripe, and over-ripe) to outline VOCs dynamic during fruit
      development. The objective of the second experiment was to confirm the analytical
      capability of PTR-ToF-MS to profile blueberry genotypes and to identify the most
      characterizing VOCs. In this case, 11 accessions belonging to different Vaccinium
      species were employed: V. corymbosum L. ("Brigitta," "Chandler," "Liberty," and
      "Ozark Blue"), V. virgatum Aiton ("Centurion," "Powder Blue," and "Sky Blue"), V.
      myrtillus L. (three wild genotypes of different mountain locations), and one
      accession of V. cylindraceum Smith. This comprehensive characterization of
      blueberry aroma allowed the identification of a wide pull of VOCs, for the most
      aldehydes, alcohols, terpenoids, and esters that can be used as putative
      biomarkers to rapidly evaluate the blueberry aroma variations related to ripening
      and/or senescence as well as to genetic background differences. Moreover, the
      obtained results demonstrated the complementarity between chromatographic and
      direct-injection mass spectrometric techniques to study the blueberry aroma.

PMID- 28491070
TI  - Ascorbic Acid-A Potential Oxidant Scavenger and Its Role in Plant Development and
      Abiotic Stress Tolerance.
AB  - Over-production of reactive oxygen species (ROS) in plants under stress
      conditions is a common phenomenon. Plants tend to counter this problem through
      their ability to synthesize ROS neutralizing substances including non-enzymatic
      and enzymatic antioxidants. In this context, ascorbic acid (AsA) is one of the
      universal non-enzymatic antioxidants having substantial potential of not only
      scavenging ROS, but also modulating a number of fundamental functions in plants
      both under stress and non-stress conditions. In the present review, the role of
      AsA, its biosynthesis, and cross-talk with different hormones have been discussed
      comprehensively. Furthermore, the possible involvement of AsA-hormone crosstalk
      in the regulation of several key physiological and biochemical processes like
      seed germination, photosynthesis, floral induction, fruit expansion, ROS
      regulation and senescence has also been described. A simplified and schematic AsA
      biosynthetic pathway has been drawn, which reflects key intermediates involved
      therein. This could pave the way for future research to elucidate the modulation
      of plant AsA biosynthesis and subsequent responses to environmental stresses.
      Apart from discussing the role of different ascorbate peroxidase isoforms, the
      comparative role of two key enzymes, ascorbate peroxidase (APX) and ascorbate
      oxidase (AO) involved in AsA metabolism in plant cell apoplast is also discussed
      particularly focusing on oxidative stress perception and amplification. Limited
      progress has been made so far in terms of developing transgenics which could over
      produce AsA. The prospects of generation of transgenics overexpressing AsA
      related genes and exogenous application of AsA have been discussed at length in
      the review.

PMID- 28491072
TI  - ThNAC13, a NAC Transcription Factor from Tamarix hispida, Confers Salt and
      Osmotic Stress Tolerance to Transgenic Tamarix and Arabidopsis.
AB  - NAC (NAM, ATAF1/2, and CUC2) proteins play critical roles in many plant
      biological processes and environmental stress. However, NAC proteins from Tamarix
      hispida have not been functionally characterized. Here, we studied a NAC gene
      from T. hispida, ThNAC13, in response to salt and osmotic stresses. ThNAC13 is a
      nuclear protein with a C-terminal transactivation domain. ThNAC13 can bind to NAC
      recognized sites and calmodulin-binding NAC (CBNAC) binding element.
      Overexpression of ThNAC13 in Arabidopsis improved seed germination rate and
      increased root growth and fresh weight gain under salt or osmotic stress.
      Transgenic T. hispida plants transiently overexpressing ThNAC13 and with RNAi
      silenced ThNAC13 were generated for gain- and loss-of-function experiments.
      Following exposure to salt or osmotic stress, overexpression of ThNAC13 induced
      superoxide dismutase (SOD) and peroxidase (POD) activities, chlorophyll and
      proline contents; decreased the reactive oxygen species (ROS) and malondialdehyde
      levels; and reduced electrolyte leakage rates in both transgenic Tamarix and
      Arabidopsis plants. In contrast, RNAi-silenced ThNAC13 showed the opposite
      results in transgenic Tamarix. Furthermore, ThNAC13 induced the expression of
      SODs and PODs in transgenic Arabidopsis. These results suggest that ThNAC13
      improves salt and osmotic tolerance by enhancing the ROS-scavenging capability
      and adjusting osmotic potential.

PMID- 28491074
TI  - Editorial: Plant Competition in a Changing World.

PMID- 28491073
TI  - Regulation of Translation by TOR, eIF4E and eIF2alpha in Plants: Current
      Knowledge, Challenges and Future Perspectives.
AB  - An important step in eukaryotic gene expression is the synthesis of proteins from
      mRNA, a process classically divided into three stages, initiation, elongation,
      and termination. Translation is a precisely regulated and conserved process in
      eukaryotes. The presence of plant-specific translation initiation factors and the
      lack of well-known translational regulatory pathways in this kingdom nonetheless
      indicate how a globally conserved process can diversify among organisms. The
      control of protein translation is a central aspect of plant development and
      adaptation to environmental stress, but the mechanisms are still poorly
      understood. Here we discuss current knowledge of the principal mechanisms that
      regulate translation initiation in plants, with special attention to the
      singularities of this eukaryotic kingdom. In addition, we highlight the major
      recent breakthroughs in the field and the main challenges to address in the
      coming years.

PMID- 28491075
TI  - Saturation Mapping of a Major Effect QTL for Stripe Rust Resistance on Wheat
      Chromosome 2B in Cultivar Napo 63 Using SNP Genotyping Arrays.
AB  - Stripe rust or yellow rust (YR), caused by Puccinia striiformis f. sp. tritici
      (Pst), is one of the most important diseases of wheat (Triticum aestivum L.).
      Widespread deployment of resistant cultivars is the best means of achieving
      durable disease control. The red grain, spring wheat cultivar Napo 63 produced by
      CIMMYT in the 1960s shows a high level of adult-plant resistance to stripe rust
      in the field. To elucidate the genetic basis of resistance in this cultivar we
      evaluated 224 F2:3 lines and 175 F2:6 recombinant inbred lines (RILs) derived
      from a cross between Napo 63 and the Pst-susceptible line Avocet S. The maximum
      disease severity (MDS) data of F2:3 lines and the relative area under the disease
      progress curve (rAUDPC) data of RILs were collected during the 2014-2015 and 2015
      2016 wheat growing seasons, respectively. Combined bulked segregant analysis and
      90K single nucleotide polymorphism (SNP) arrays placed 275 of 511 polymorphic
      SNPs on chromosome 2B. Sixty four KASP markers selected from the 275 SNPs and 76
      SSR markers on 2B were used to identify a chromosome region associated with rust
      response. A major effect QTL, named Qyrnap.nwafu-2BS, was identified by inclusive
      composite interval mapping and was preliminarily mapped to a 5.46 cM interval
      flanked by KASP markers 90K-AN34 and 90K-AN36 in chromosome 2BS. Fourteen KASP
      markers more closely linked to the locus were developed following a 660K SNP
      array analysis. The QTL region was finally narrowed to a 0.9 cM interval flanked
      by KASP markers 660K-AN21 and 660K-AN57 in bin region 2BS-1-0.53. The resistance
      of Napo 63 was stable across all environments, and as a QTL, explained an average
      66.1% of the phenotypic variance in MDS of F2:3 lines and 55.7% of the phenotypic
      variance in rAUDPC of F5:6 RILs. The short genetic interval and flanking KASP
      markers developed in the study will facilitate marker-assisted selection, gene
      pyramiding, and eventual positional cloning of Qyrnap.nwafu-2BS.

PMID- 28491077
TI  - How Should Plant Resistance to Herbivores Be Measured?

PMID- 28491076
TI  - A Proteomic Approach Suggests Unbalanced Proteasome Functioning Induced by the
      Growth-Promoting Bacterium Kosakonia radicincitans in Arabidopsis.
AB  - Endophytic plant growth-promoting bacteria have significant impact on the plant
      physiology and understanding this interaction at the molecular level is of
      particular interest to support crop productivity and sustainable production
      systems. We used a proteomics approach to investigate the molecular mechanisms
      underlying plant growth promotion in the interaction of Kosakonia radicincitans
      DSM 16656 with Arabidopsis thaliana. Four weeks after the inoculation, the
      proteome of roots from inoculated and control plants was compared using two
      dimensional gel electrophoresis and differentially abundant protein spots were
      identified by liquid chromatography tandem mass spectrometry. Twelve protein
      spots were responsive to the inoculation, with the majority of them being related
      to cellular stress reactions. The protein expression of 20S proteasome alpha-3
      subunit was increased by the presence of K. radicincitans. Determination of
      proteasome activity and immuno blotting analysis for ubiquitinated proteins
      revealed that endophytic colonization interferes with ubiquitin-dependent protein
      degradation. Inoculation of rpn12a, defective in a 26S proteasome regulatory
      particle, enhanced the growth-promoting effect. This indicates that the plant
      proteasome, besides being a known target for plant pathogenic bacteria, is
      involved in the establishment of beneficial interactions of microorganisms with
      plants.

PMID- 28491078
TI  - The Importance of Being on Time: Regulatory Networks Controlling Photoperiodic
      Flowering in Cereals.
AB  - Flowering is the result of the coordination between genetic information and
      environmental cues. Gene regulatory networks have evolved in plants in order to
      measure diurnal and seasonal variation of day length (or photoperiod), thus
      aligning the reproductive phase with the most favorable season of the year. The
      capacity of plants to discriminate distinct photoperiods classifies them into
      long and short day species, depending on the conditions that induce flowering.
      Plants of tropical origin and adapted to short day lengths include rice, maize,
      and sorghum, whereas wheat and barley were originally domesticated in the Fertile
      Crescent and are considered long day species. In these and other crops, day
      length measurement mechanisms have been artificially modified during
      domestication and breeding to adapt plants to novel areas, to the extent that a
      wide diversity of responses exists within any given species. Notwithstanding the
      ample natural and artificial variation of day length responses, some of the basic
      molecular elements governing photoperiodic flowering are widely conserved.
      However, as our understanding of the underlying mechanisms improves, it becomes
      evident that specific regulators exist in many lineages that are not shared by
      others, while apparently conserved components can be recruited to novel functions
      during evolution.

PMID- 28491079
TI  - Similar Morphologies but Different Origins: Hybrid Status of Two More Semi
      creeping Taxa of Melastoma.
AB  - Inferring the origins of hybrid taxa based on morphology alone is difficult
      because morphologically similar hybrids can arise from hybridization between
      different populations of the same parental species or be produced by
      hybridization of different parental species. In this study, we investigated the
      origins of two semi-creeping taxa in Melastoma, which are morphologically similar
      to a natural hybrid, M. intermedium, by sequencing a chloroplast intergenic
      spacer, nuclear ribosomal internal transcribed spacer and two low-copy nuclear
      genes (tpi and cam) in these taxa and their putative parental species. Our
      sequence analysis provides compelling evidence for the hybrid status of the two
      semi-creeping taxa: one originating from hybridization between M. dodecandrum and
      M. malabathricum, and the other between M. dodecandrum and M. normale. The
      origins of these hybrids are therefore clearly different from M. intermedium, and
      morphological similarity for the three hybrids is most likely due to their
      origins from hybridization between the same creeping species M. dodecandrum and a
      different erect species in each of the three cases. We also observed low rate of
      introgression from M. normale to M. dodecandrum, and genetic exchange between
      them may transfer adaptive traits to M. dodecandrum. Rare occurrence of these two
      hybrids may be due to small range overlaps between parental species in one case,
      and different flowering periods between parental species in the other.

PMID- 28491080
TI  - Corrigendum: Making Plants Break a Sweat: the Structure, Function, and Evolution
      of Plant Salt Glands.
AB  - [This corrects the article on p. 406 in vol. 8, PMID: 28400779.].

PMID- 28491081
TI  - Safety and efficacy of transradial coronary angiography and intervention in
      patients older than 80 years: from the Korean Transradial Intervention
      Prospective Registry.
AB  - BACKGROUND: Radial artery access for coronary procedures is a safe and beneficial
      technique. However, elderly patients have been considered as a higher risk group
      of access site related complications compared to younger patients. This study was
      conducted to investigate the feasibility and safety of transradial coronary
      angiography or intervention in the elderly. METHODS: A total of 6132 patients
      from Korean Transradial Intervention Prospective Registry at 20 centers were
      analyzed. Patients were divided into the non-elderly group (n = 5667) and the
      elderly (>= 80 years) group (n = 465). Using propensity score matching, the
      elderly group (n = 465) was compared with one-to-one matched the non-elderly
      group (n = 465). RESULTS: After propensity score matching, mean age was 64.3 +/-
      10.3 years in the non-elderly group and 83.5 +/- 3.3 years in the elderly group.
      There was no difference of procedural characteristics, procedural and
      fluoroscopic times. Access site cross-over rate was not different between the non
      elderly group and elderly group (7.5% vs. 6.2%, P = 0.074). Bleeding
      complications occurred similarly in two groups (2.6% of the non-elderly group vs.
      1.9% of the elderly group, P = 0.660). Access site complications were 1.9% of the
      non-elderly group and 0.9% of the elderly group (P = 0.263). Both of in hospital
      death and cardiovascular death for one year were also similar between two groups.
      CONCLUSIONS: Transradial angiography or intervention was safe and feasible in
      elderly patients. Complication rates and clinical outcomes in elderly patients
      were comparable with those in non-elderly patients.

PMID- 28491082
TI  - Altered serum level of cartilage oligomeric matrix protein and its association
      with coronary calcification in patients with coronary heart disease.
AB  - BACKGROUND: Cartilage oligomeric matrix protein (COMP) is mainly found in the
      skeletal system and vascular smooth muscle cells. Recent researches showed that
      it had a protective function on blood vessels and could also inhibit vascular
      calcification. We investigated the serum COMPs in coronary heart disease (CHD)
      patients, and the relationship between serum COMP and the calcification of
      coronary artery. METHODS: A total of 233 consecutive chest pain patients who
      first underwent coronary angiography followed by multi-slice computed tomography
      (MSCT) within six months were recruited and divided into two groups according to
      the coronary angiography luminal diameter narrowing percentages: CHD group
      (diameter narrowing >= 50%, n = 194) and control group (diameter narrowing < 50%,
      n = 39). The Gensini score, Syntax score and coronary artery calcium score (CACs)
      were calculated. The serum COMP level was determined using ELISA. RESULTS: The
      levels of COMP were significantly higher in the CHD group than in the control
      group 155.7 (124.5-194.5) ng/mL vs. 128.4 (113.0-159.9) ng/mL, P = 0.019. There
      were no correlation between COMP, Gensini score, Syntax score, severity of
      coronary stenosis and the number of coronary artery with stenosis > 50%. The
      serum COMP was correlated with age (r = 0.294, P < 0.001), fasting glucose (r =
      0.163, P = 0.015), HbA1c (r = 0.194, P = 0.015) and CACs (r = 0.137, P = 0.037).
      Stepwise linear regression analysis showed that COMP level and age were
      independent predictors of CACs in the CHD patients (beta = 0.402, t = 2.612, P =
      0.015; beta = 0.472, t = 3.077, P = 0.005). Performance of COMP for predicting
      CHD was shown as area under curve (AUC): 0.632, 95% CI: 0.549-0.715 and upper
      tertile CACs was AUC: 0.602, 95% CI: 0.526-0.678 in receiver operating
      characteristic (ROC) curve analysis. CONCLUSION: Calcification of coronary artery
      was an independent predictor of serum COMPs.

PMID- 28491083
TI  - Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION
      bleeding scores in ACS patients undergoing PCI: insights from a cohort of 4939
      patients in China.
AB  - BACKGROUND: The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for
      predicting in-hospital major bleeding events in patients with acute coronary
      syndrome (ACS), but the homogeneous nature of these models' population limits
      simple extrapolation to other local population. We aimed to compare the
      performance of the three risk models in Chinese patients. METHODS: We evaluated
      the performance of the three predicting scores for predicting in-hospital major
      bleeding events defined by thrombolysis in myocardial infarction (TIMI) serious
      (major and minor) episodes, in a cohort of Chinese ACS patients with either non
      ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI).
      Calibration and discrimination of the three risk models were evaluated by the
      Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive
      accuracy of the risk scores by the Delong non-parametric test. RESULTS: TIMI
      serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS,
      respectively). The CRUSADE, ACTION and ACUTIY-HORIZONS scores showed an adequate
      discriminatory capacity for major bleeding: in overall patients, the C-statistic
      was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was
      0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91,
      0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was
      significantly lower than those of the CRUSADE and ACTION scores for the
      prediction of TIMI serious bleeding in overall patients (compared with CRUSADE, z
      = 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients
      (compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P =
      0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02;
      compared with ACTION, z = 7.91, P = 0.002). No differences were observed when the
      CRUSADE and ACTION models were compared to each other, regardless of overall
      patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P =
      0.60), and STEMI patients (z = 0.36, P = 0.74). However, the three risk scores
      all overestimated the absolute major bleeding risk in each risk stratification in
      our study. For example, the predicted rate of CRUSADE score at high risk
      stratification was 11.9% vs. an actual rate of 5.3%. CONCLUSIONS: The CRUSADE and
      ACTION scores had a greater calibration and discrimination for in-hospital major
      bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS
      undergoing PCI. However, they all overestimated the bleeding risk rate for
      Chinese populations. Calibration of these risk scores would be useful for the
      generalization in Chinese populations.

PMID- 28491084
TI  - The impact of optimal medical therapy at discharge on mortality in patients with
      coronary artery disease.
AB  - OBJECTIVE: To analyze the current usage of optimal medical therapy (OMT),
      influencing factors, and the predictive value of OMT for all-cause mortality in
      coronary artery disease (CAD) patients with different subgroups. METHODS: A total
      of 3176 CAD patients confirmed by coronary angiography were included. OMT was
      defined as the combination of anti-platelet drugs, statins, beta blockers, and
      angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
      Factors for OMT and its prognostic value were analyzed in CAD patients across
      different subgroups. RESULTS: Out of 3176 patients, only 39.8% (n = 1265) were on
      OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT
      and discharge department. All-cause mortality occurred in 6.8% (n = 217) of
      patients. Multivariate analyses indicated that OMT was significantly associated
      with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45-0.95; P = 0.025). Sub
      group analyses indicate that male acute coronary syndrome (ACS) patients were
      more likely to receive survival benefits with OMT at discharge. The positive
      impact of OMT at discharge was more apparent after 24 months, regardless of
      revascularization therapy. Four-drug combination of OMT was superior to 3-drug
      combination therapy in ACS patients but not in stable patients. CONCLUSIONS: OMT
      was associated with significant improvement in survival in patients with CAD. The
      positive impact of OMT was distinct in the CAD patients with different
      characteristics.

PMID- 28491085
TI  - Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in
      acute ST-segment elevation myocardial infarction: a multicenter randomized
      clinical trial.
AB  - BACKGROUND: The benefit/risk ratio of stenting in acute ST-segment elevation
      myocardial infarction (STEMI) patients with single vessel intermediate stenosis
      culprit lesions merits further study, therefore the subject of the present study.
      METHODS AND RESULTS: It was a prospective, multicenter, randomized controlled
      trial. Between April 2012 and July 2015, 399 acute STEMI patients with single
      vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before
      or after aspiration thrombectomy and/or intracoronary tirofiban (15 ug/kg) were
      enrolled and were randomly assigned (1: 1) to stenting group (n = 201) and non
      stenting group (n = 198). In stenting group, patients received pharmacologic
      therapy plus standard percutaneous coronary intervention (PCI) with stent
      implantation. In non-stenting group, patients received pharmacologic therapy and
      PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12
      month rate of major adverse cardiac and cerebrovascular events (MACCE), a
      composite of cardiac death, non-fatal myocardial infarction (MI), repeat
      revascularization and stroke. Secondary endpoints were 12-month rates of all
      cause death, ischemia driven admission and bleeding complication. Median follow
      up time was 12.4 +/- 3.1 months. At 12 months, MACCE occurred in 8.0% of the
      patients in stenting group, as compared with 15.2% in the non-stenting group
      (adjusted HR: 0.42, 95% CI: 0.19-0.89, P = 0.02). The stenting group had lower
      non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two
      groups shared similar cardiac death, repeat revascularization, stroke, all cause
      death, ischemia driven readmission and bleeding rates at 12 months. CONCLUSIONS:
      Stent implantation had better efficacy and safety in reducing MACCE risks among
      acute STEMI patients with single vessel intermediate stenosis culprit lesions.

PMID- 28491086
TI  - Left univentricular pacing for cardiac resynchronization therapy using rate
      adaptive atrioventricular delay.
AB  - OBJECTIVE: To evaluate left univentricular (LUV) pacing for cardiac
      resynchronization therapy (CRT) using a rate-adaptive atrioventricular delay
      (RAAVD) algorithm to track physiological atrioventricular delay (AVD). METHODS: A
      total of 72 patients with congestive heart failure (CHF) were randomized to RAAVD
      LUV pacing versus standard biventricular (BiV) pacing in a 1: 1 ratio.
      Echocardiography was used to optimize AVD for both groups. The effects of
      sequential BiV pacing and LUV pacing with optimized A-V (right atrio-LV) delay
      using an RAAVD algorithm were compared. The standard deviation (SD) of the S/R
      ratio in lead V1 at five heart rate (HR) segments (RS/R-SD5), defined as the
      "tracking index," was used to evaluate the accuracy of the RAAVD algorithm for
      tracking physiological AVD. RESULTS: The QRS complex duration (132 +/- 9.8 vs.
      138 +/- 10 ms, P < 0.05), the time required for optimization (21 +/- 5 vs. 50 +/-
      8 min, P < 0.001), the mitral regurgitant area (1.9 +/- 1.1 vs. 2.5 +/- 1.3 cm2,
      P < 0.05), the interventricular mechanical delay time (60.7 +/- 13.3 ms vs. 68.3
      +/- 14.2 ms, P < 0.05), and the average annual cost (13,200 +/- 1000 vs. 21,600
      +/- 2000 RMB, P < 0.001) in the RAAVD LUV pacing group were significantly less
      than those in the standard BiV pacing group. The aortic valve velocity-time
      integral in the RAAVD LUV pacing group was greater than that in the standard BiV
      pacing group (22.7 +/- 2.2 vs. 21.4 +/- 2.1 cm, P < 0.05). The RS/R-SD5 was 4.08
      +/- 1.91 in the RAAVD LUV pacing group, and was significantly negatively
      correlated with improved left ventricular ejection fraction (LVEF) (DeltaLVEF,
      Pearson's r = -0.427, P = 0.009), and positively correlated with New York Heart
      Association class (Spearman's r = 0.348, P = 0.037). CONCLUSIONS: RAAVD LUV
      pacing is as effective as standard BiV pacing, can be more physiological than
      standard BiV pacing, and can decrease the average annual cost of CRT.

PMID- 28491087
TI  - Neutrophil-to-lymphocyte ratio compared to N-terminal pro-brain natriuretic
      peptide as a prognostic marker of adverse events in elderly patients with chronic
      heart failure.
AB  - BACKGROUND: The neutrophil-to-lymphocyte (N/L) ratio has been associated with
      poor prognosis in patients with heart failure, but it has not been compared with
      N-terminal pro-brain natriuretic peptide (NT-proBNP) in elderly patients with
      chronic heart failure (CHF). We sought to make this comparison. METHODS: A total
      of 1355 elderly patients with CHF were analyzed. A multivariate logistic
      regression model was used to analyze the variables associated with atrial
      fibrillation (AF). Cox regression analysis was used to assess the multivariable
      relationship between the N/L ratio, NT-proBNP level, and subsequent major
      cardiovascular events (MCE). RESULTS: In the multiple logistic regression
      analysis, the N/L ratio was demonstrated as a risk factor for AF in elderly
      patients with CHF [odds ratio (OR): 1.079, 95% confidence interval (CI): 1.027
      1.134, P = 0.003]. The median follow-up period was 18 months. In a multivariable
      model using tertiles of both variables, the highest tertile of the N/L ratio was
      significantly associated with MCE [hazard ratio (HR): 1.407, 95% CI: 1.098-1.802,
      P = 0.007] compared with the lowest tertile. Similarly, the highest NT-proBNP
      tertile was also significantly associated with MCE (HR: 1.461, 95% CI: 1.104
      1.934, P = 0.008). CONCLUSIONS: In elderly patients with CHF, the N/L ratio is
      one of the important risk factors for AF and it is an inexpensive and readily
      available marker with similar independent prognostic power to NT-proBNP. The risk
      of MCE increases 1.407-fold when the N/L ratio is elevated to the highest
      tertile.

PMID- 28491089
TI  - Successful treatment of intracardiac air embolism using intracardiac catheter
      aspiration.

PMID- 28491090
TI  - Recurrent acute myocardial infarction and atrial fibrillation.

PMID- 28491088
TI  - Novel biomarkers for cardiovascular risk prediction.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability
      worldwide. The primary prevention of CVD is dependent upon the ability to
      identify high-risk individuals long before the development of overt events. This
      highlights the need for accurate risk stratification. An increasing number of
      novel biomarkers have been identified to predict cardiovascular events.
      Biomarkers play a critical role in the definition, prognostication, and decision
      making regarding the management of cardiovascular events. This review focuses on
      a variety of promising biomarkers that provide diagnostic and prognostic
      information. The myocardial tissue-specific biomarker cardiac troponin, high
      sensitivity assays for cardiac troponin, and heart-type fatty acid binding
      proteinall help diagnose myocardial infarction (MI) in the early hours following
      symptoms. Inflammatory markers such as growth differentiation factor-15, high
      sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death.
      Pregnancy-associated plasma protein A, myeloperoxidase, and matrix
      metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein
      associated phospholipase A2 and secretory phospholipase A2 predict incident and
      recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2,
      endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all
      been well validated to predict death and heart failure following a MI and provide
      risk stratification information for heart failure. Rapidly developing new areas,
      such as assessment of micro-RNA, are also explored. All the biomarkers reflect
      different aspects of the development of atherosclerosis.

PMID- 28491091
TI  - Identification of Functionally Interconnected Neurons Using Factor Analysis.
AB  - The advances in electrophysiological methods have allowed registering the joint
      activity of single neurons. Thus, studies on functional dynamics of complex
      valued neural networks and its information processing mechanism have been
      conducted. Particularly, the methods for identifying neuronal interconnections
      are in increasing demand in the area of neurosciences. Here, we proposed a factor
      analysis to identify functional interconnections among neurons via spike trains.
      This method was evaluated using simulations of neural discharges from different
      interconnections schemes. The results have revealed that the proposed method not
      only allows detecting neural interconnections but will also allow detecting the
      presence of presynaptic neurons without the need of the recording of them.

PMID- 28491092
TI  - Can Transabdominal Scan Predict a Short Cervix by Transvaginal Scan?
AB  - Background. To determine whether transabdominal screening can be used to screen
      women with short cervix on transvaginal scan. Methods. The study was done between
      18 and 20 weeks of gestation. Transabdominal scan was done and cervical length
      was measured. Transvaginal scan was also done and cervical length was measured.
      An attempt was made to find out whether transabdominal scan be used to predict a
      cervical length of 25 mm by transvaginal scan. Results. In our study the cut-off
      for transabdominal scan for detecting a short cervix of 25 mm by transvaginal
      scan was 29 mm. A transabdominal cervical length of 29 mm could predict a short
      cervix of 25 mm by transvaginal scan by 100% sensitivity and 92.4% sensitivity.
      Conclusion. A cut-off of 29 mm by transabdominal scan is very accurate in
      predicting a short cervix of 25 mm by transvaginal scan.

PMID- 28491093
TI  - Therapeutic Effect and Location of GFP-Labeled Placental Mesenchymal Stem Cells
      on Hepatic Fibrosis in Rats.
AB  - Background. Liver fibrosis is a chronic progressive liver disease, but no
      established effective treatment exists except for liver transplantation. The
      present study was designed to investigate the effect of human placenta
      mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) on
      carbon tetrachloride- (CCl4-) induced liver fibrosis in rats. Methods. Liver
      fibrosis was induced by subcutaneous injection with CCl4; hPMSCs were directly
      transplanted into rats through the caudal vein. The therapeutic efficacy of
      hPMSCs on liver fibrosis was measured by liver function tests, liver
      elastography, histopathology, Masson's trichrome and Sirius red staining, and
      immunohistochemical studies. The expression levels of fibrotic markers,
      transforming growth factor beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha
      SMA), were assessed using real-time polymerase chain reaction. Results. We
      demonstrated that liver fibrosis was significantly dampened in the hPMSC
      transplantation group according to the Laennec fibrosis scoring system and
      histological data. The Sirius red-stained collagen area and the elastography
      score were significantly reduced in the hPMSC-treated group. Meanwhile, hPMSC
      administration significantly decreased TGF-beta1 and alpha-SMA expression and
      enhanced liver functions in CCl4-induced fibrotic rats. Conclusion. This study
      indicates that transplantation of hPMSCs could repair liver fibrosis induced by
      CCl4 in rats, which may serve as a valuable therapeutic approach to treat liver
      diseases.

PMID- 28491094
TI  - Immunoprofiling of Adult-Derived Human Liver Stem/Progenitor Cells: Impact of
      Hepatogenic Differentiation and Inflammation.
AB  - Adult-derived human liver stem/progenitor cells (ADHLSCs) are, nowadays,
      developed as therapeutic medicinal product for the treatment of liver defects. In
      this study, the impact of hepatogenic differentiation and inflammation priming on
      the ADHLSCs' immune profile was assessed in vitro and compared to that of mature
      hepatocytes. The constitutive immunological profile of ADHLSCs was greatly
      different from that of hepatocytes. Differences in the expression of the stromal
      markers CD90 and CD105, adhesion molecules CD44 and CD49e, immunoregulatory
      molecules CD73 and HO-1, and NK ligands CD112 and CD155 were noted. While they
      globally preserved their immunological profile in comparison to undifferentiated
      counterparts, differentiated ADHLSCs showed a significant downregulation of CD200
      expression as in hepatocytes. This was mainly induced by signals issued from EGF
      and OSM. On the other hand, the impact of inflammation was quite similar for all
      studied cell populations with an increased expression level of CD54 and CD106 and
      induction of that of CD40 and CD274. In conclusion, our immune profiling study
      suggests CD200 as a key factor in regulating the immunobiology of differentiated
      ADHLSCs. A better understanding of the molecular and physiological events related
      to such marker could help in designing the optimal conditions for an efficient
      therapeutic use of ADHLSCs.

PMID- 28491095
TI  - Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in
      D-Galactose-Induced Aging Mouse Model.
AB  - Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits
      replenishment of the blood and immune system and hence contributes to
      hematopoietic diseases and declined immunity. In this study, we employed D-gal
      induced aging mouse model and observed the antiaging effects of Angelica Sinensis
      Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica
      Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs
      senescence with decreased AGEs levels in the serum, reduced SA-beta-Gal positive
      cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We
      further found that multiple mechanisms were involved: (1) ASP treatment prevented
      oxidative damage as total antioxidant capacity was increased and levels of
      reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced
      the expression of gamma-H2A.X which is a DNA double strand breaks (DSBs) marker
      and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and
      p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive
      activation of Wnt/beta-catenin signaling in aged HSC/HPCs, as the expressions of
      beta-catenin, phospho-GSK-3beta, and TCF-4 were decreased, and the cyto-nuclear
      translocation of beta-catenin was inhibited. Moreover, compared with the positive
      control of Vitamin E, ASP exhibited a better antiaging effect and a weaker
      antioxidation ability, suggesting a novel protective role of ASP in the
      hematopoietic system.

PMID- 28491096
TI  - Cardiovascular Regeneration: Biology and Therapy.

PMID- 28491097
TI  - Wnt5a Signaling in Normal and Cancer Stem Cells.
AB  - Wnt5a is involved in activating several noncanonical Wnt signaling pathways,
      which can inhibit or activate canonical Wnt/beta-catenin signaling pathway in a
      receptor context-dependent manner. Wnt5a signaling is critical for regulating
      normal developmental processes, including stem cell self-renewal, proliferation,
      differentiation, migration, adhesion, and polarity. Moreover, the aberrant
      activation or inhibition of Wnt5a signaling is emerging as an important event in
      cancer progression, exerting both oncogenic and tumor suppressive effects. Recent
      studies show the involvement of Wnt5a signaling in regulating normal and cancer
      stem cell self-renewal, cancer cell proliferation, migration, and invasion. In
      this article, we review recent findings regarding the molecular mechanisms and
      roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or
      neoplastic breast or ovary, highlighting that Wnt5a may have different effects on
      target cells depending on the surface receptors expressed by the target cell.

PMID- 28491098
TI  - Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from
      Pluripotent Stem Cells.
AB  - Human pluripotent stem cells (hPSCs) have the capacity to differentiate into
      essentially all cell types in the body. Such differentiation can be directed to
      specific cell types by appropriate cell culture conditions or overexpressing
      lineage-defining transcription factors (TFs). Especially, for the activation of
      myogenic program, early studies have shown the effectiveness of enforced
      expression of TFs associated with myogenic differentiation, such as PAX7 and
      MYOD1. However, the efficiency of direct differentiation was rather low, most
      likely due to chromatin features unique to hPSCs, which hinder the access of TFs
      to genes involved in muscle differentiation. Indeed, recent studies have
      demonstrated that ectopic expression of epigenetic-modifying factors such as a
      histone demethylase and an ATP-dependent remodeling factor significantly enhances
      myogenic differentiation from hPSCs. In this article, we review the recent
      progress for in vitro generation of skeletal muscles from hPSCs through forced
      epigenetic and transcriptional manipulation.

PMID- 28491099
TI  - Induction of Pluripotent Stem Cells from a Manifesting Carrier of Duchenne
      Muscular Dystrophy and Characterization of Their X-Inactivation Status.
AB  - Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD)
      develop dystrophic symptoms ranging from mild muscle weakness to a rapidly
      progressive DMD-like muscular dystrophy due to skewed inactivation of X
      chromosomes during early development. Here, we generated human induced
      pluripotent stem cells (hiPSCs) from a manifesting female carrier using
      retroviral or Sendai viral (SeV) vectors and determined their X-inactivation
      status. Although manifesting carrier-derived iPS cells showed normal expression
      of human embryonic stem cell markers and formed well-differentiated teratomas in
      vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR)
      gene and loss of X-inactivation-specific transcript and trimethyl-histone H3
      (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS
      cells are in an active state. Importantly, normal dystrophin was expressed in
      multinucleated myotubes differentiated from a manifesting carrier of DMD-hiPS
      cells with XaXa pattern. AR transcripts were also equally transcribed from both
      alleles in induced myotubes. Our results indicated that the inactivated X
      chromosome in the patient's fibroblasts was activated during reprogramming, and
      XCI occurred randomly during differentiation.

PMID- 28491100
TI  - Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing
      following Hurricanes.
AB  - Objective. To report on changes in sensitivity to mold allergens determined by
      changes in intradermal skin testing reactivity, after exposure to two severe
      hurricanes. Methods. A random, retrospective allergy charts review divided into 2
      groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior
      to hurricanes, and Group B, patients tested in 2014 and 2015 following
      hurricanes. Reactivity to eighteen molds was determined by intradermal skin
      testing. Test results, age, and respiratory symptoms were recorded. Chi-square
      test determined reactivity/sensitivity differences between groups. Results.
      Posthurricane patients had 34.6 times more positive results (p < 0.0001) at
      weaker dilutions, all tested molds were found to be more reactive, and 95% had at
      least one positive test versus only 62% before the hurricanes (p < 0.0001);
      average mold reactivity was 55% versus 16% while 17% of patients reacted to the
      entire panel versus none before the hurricanes (p < 0.0001). The posthurricane
      population was younger (p < 0.001) and included more patients with asthma or
      lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization
      to mold allergens increased compared to patients before the hurricanes. This
      supports climatologists' hypothesis that environmental changes resulting from
      hurricanes can be a health risk as reflected in increased allergic sensitivities
      and symptoms and has significant implications for physicians treating patients
      from affected areas.

PMID- 28491101
TI  - Geospatial Assessment of Cholera in a Rapidly Urbanizing Environment.
AB  - This study mapped out and investigated the spatial relationship between cholera
      incidences and environmental risk factors in the study area. The study area was
      stratified into eight zones. Water samples from each zone were collected and
      analyzed to determine the colony forming units. GIS layers including housing
      density, digitized roads, rivers, buildings, and cholera incidence data from
      hospital archives were also collected and analyzed using ArcGIS 10.1. It was
      observed that there was an association between the ERFs (p < 0.001). Similarly,
      18 out of the 44 waste dump sites, seven out of 18 markets, and two out of 36
      abattoirs were found near the historical cholera cases. Similarly, 4 (21.1%)
      locations were traced to be predominantly close to rivers and waste dump site.
      All the historical cholera cases were found adjoining to roads and buildings.
      Highest CFU count was found in the wells and streams of areas with a cluster of
      all the environmental risk factors and high housing density. This study revealed
      that waste dump sites and market had the highest predisposing attribute while the
      least was abattoir. The uniqueness of the study lies in the combination of
      mapping and microbial analyses to identify and assess the pattern of cholera risk
      and also to provide clear information for development of strategies for
      environmental supervision.

PMID- 28491102
TI  - The relationship between circulating concentrations of interleukin 17 and C
      reactive protein in chronic spontaneous urticaria.
AB  - BACKGROUND: Up-regulation of interleukin 17 (IL-17) family cytokines and acute
      phase response have been observed in patients with chronic spontaneous urticaria
      (CSU). It has been demonstrated that IL-17 stimulates C-reactive protein (CRP)
      expression. AIM: To determine relationship between circulating concentrations of
      IL-17 and CRP in CSU. METHODS: Concentrations of IL-17 in plasma and CRP in serum
      were measured in patients with CSU of varying severity and in the healthy
      subjects. RESULTS: IL-17 and CRP concentrations were significantly higher in CSU
      patients as compared to the healthy subjects. In addition, there were significant
      differences in IL-17 and CRP concentrations between CSU patients with mild,
      moderate-severe symptoms and the healthy subjects. CRP did not correlate
      significantly with IL-17. CONCLUSIONS: Increased circulating IL-17 concentration
      may represent an independent index of systemic inflammatory response in CSU,
      which is not related to increased CRP concentration.

PMID- 28491103
TI  - Oleuropein Protects Cardiomyocyte against Apoptosis via Activating the
      Reperfusion Injury Salvage Kinase Pathway In Vitro.
AB  - Oleuropein, the main glycoside present in olives, has been reported to have
      cardioprotective effect, but the exact mechanism has not been clearly elucidated.
      This study attempted to clarify the cardioprotective effect of oleuropein against
      simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and
      further explore the underlying mechanism. Here we confirmed that oleuropein
      reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced
      by decreasing MTT dye reduction and LDH activity in the culture medium.
      Meanwhile, the compound also inhibited reactive oxygen species excessive
      generation and stabilized mitochondrial membrane potential after SI/R. The flow
      cytometry assessment results indicated the inhibition of cellular apoptosis with
      oleuropein treatment. Furthermore, western blot analysis showed that oleuropein
      attenuated the expression of Cyt-C, c-caspase-3, and c-caspase-9, increased the
      Bcl-2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R.
      However, the phosphorylation enhancement was partially abolished in the presence
      of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings
      indicate that oleuropein has the protective potential against SI/R-induced injury
      and its protective effect may be partly due to the attenuation of apoptosis via
      the activation of the PI3K/Akt and ERK1/2 signaling pathways.

PMID- 28491104
TI  - Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling
      Pathway in ApoE-/- Mice Fed with a High-Fat Diet.
AB  - Lipid metabolism dysregulation plays a crucial role in the occurrence of
      atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating
      lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM)
      for treating angina pectoris, has antiatherosclerotic effects and ameliorates
      blood lipids disturbance. However, its precise mechanism remains unclear. This
      study investigated the mechanism of TMP in ameliorating As in mice model. After
      six weeks of high-fat diet, 30 ApoE-/- mice were randomized (n = 10) and treated
      with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and
      insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c,
      IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results
      showed that TMP could significantly decrease blood lipids levels, insulin, and
      corrected plaque area of the ApoE-/- mice as compared to the untreated mice (P <
      0.05, P < 0.01). Moreover, TMP could significantly downregulate the expressions
      of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P < 0.01). Thus, TMP may
      ameliorate lipid metabolism disorder and As by downregulating PAQR3 and
      inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1
      signaling pathway may be involved in this process.

PMID- 28491105
TI  - The Impacts of Chrysanthemum indicum Extract on Oxidative Stress and Inflammatory
      Responses in Adjuvant-Induced Arthritic Rats.
AB  - Chrysanthemum indicum has been used as a therapeutic agent against inflammation,
      hypertension, and respiratory conditions for many years. This research's aim has
      been to examine the antioxidant impacts that Chrysanthemum indicum extract (CIE)
      has on the oxidative stress and inflammatory responses in adjuvant-induced
      arthritic (AA) rats. 40 rats were categorised into 4 groups according to a
      completely randomized approach: Group I involved normal control rats (CTRL) that
      received a basal diet; Group II involved arthritic control rats (CTRL-AA) that
      received the same diet; Group III involved rats that received a basal diet and 30
      mg/kg CIE; and Group IV involved arthritic rats with the same diet as Group III
      rats (CIE-AA). After injection with complete Freund's adjuvant, body weight,
      arthritis score, and the serum levels of TNF-alpha, IL-1beta, IL-6,
      myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and
      glutathione peroxidase (GSH-PX) were assessed. The results demonstrated that CIE
      delayed the onset time of arthritis and decreased the clinical arthritis severity
      score (P < 0.05). Observations of CIE-AA and CTRL-AA rats demonstrated that CIE
      alleviates oxidative stress and inflammatory responses in CIE-AA group. In
      conclusion, CIE alleviated oxidative stress and inflammatory responses, thereby
      highlighting its potential use as a candidate for clinical treatments of
      rheumatoid arthritis.

PMID- 28491106
TI  - In Vitro Antioxidant and Antimicrobial Activities of Ephedra gerardiana (Root and
      Stem) Crude Extract and Fractions.
AB  - The utilization of medicinal plants to treat infectious disease is a common
      practice in developing countries worldwide. The present study was aimed at
      evaluating the crude extracts of Ephedra gerardiana (root and stem) with
      different chemicals for antioxidant and antimicrobial (fungal and bacterial)
      potential. The results revealed that the ethyl acetate fractions of E. gerardiana
      (root and stem) have significant free radical scavenging potential with values
      2.96 +/- 0.39 and 2.73 +/- 0.84 while n-butanol and aqueous fractions showed
      IC502.69 +/- 0.26 and 3.44 +/- 0.69 ug/ml in stem. Furthermore, crude extract and
      fractions also revealed promising antibacterial activities against all tested
      microbial strains while aqueous fraction showed no activities against Bacillus
      subtilis, Kleibsiella pneumoniae, and Pseudomonas aeruginosa. Interestingly, all
      crude extracts and fractions were nonactive against fungal strain, Aspergillus
      niger and Aspergillus flavus, as compare to control. In summary, the Ephedra
      gerardiana (root and stem) extract and fraction possess antioxidant activities,
      which might be helpful in preventing or slowing the progress of various oxidative
      stresses, suggested to be a strong pharmaceutical agent.

PMID- 28491107
TI  - Characteristics of Herbal Medicine Users and Adverse Events Experienced in South
      Korea: A Survey Study.
AB  - Background. This survey aimed to investigate the characteristics of users and
      nonusers of herbal medicine and the adverse events experienced due to herbal
      medicines in South Korea. Methods. The questionnaire consisted of safety, using
      experience, using type, usage and nonusage reason, purchase location, and adverse
      events of herbal medicine. The survey was administered by online. Results. Of the
      total 1,134 respondents, 726 (64.0%) considered herbal medicine safe, and 693
      (61.1%) answered that they have taken herbal medicines within the past year. Most
      common place to purchase them was "TKM hospital or clinic" (63.6%), and most
      participants (72.2%) took a decoction from a TKM institution. The biggest reason
      for taking them was for "health improvement" (57.3%), and the reasons for not
      using them was "medication not necessary" (63.7%). Among those who took herbal
      medicines, 46 experienced adverse events, and the most frequently reported
      symptoms were digestive disorders (52.2%). Of the 46 participants who experienced
      adverse events, 20 (43.5%) were treated by TKM doctors. Conclusions. This study
      suggests that regulation of herbal medicines is needed in order to resolve
      problems related to the safety of herbal medicines.

PMID- 28491108
TI  - Electroacupuncture Improves Cognitive Deficits through Increasing Regional
      Cerebral Blood Flow and Alleviating Inflammation in CCI Rats.
AB  - Objective. To investigate the effect of EA on regional cerebral blood flow,
      cognitive deficits, inflammation, and its probable mechanisms in chronic cerebral
      ischemia (CCI) rats. Methods. Rats were assigned randomly into sham operation
      group (sham group) and operation group. For operation group, CCI model was
      performed using the permanent bilateral common carotid artery occlusion (BCCAO)
      method, and then rats were further randomly divided into model group and
      electroacupuncture (EA) group. 2/15 Hz low-frequency pulse electric intervention
      was applied at "Baihui" and "Dazhui" acupoints in EA group. Four weeks later,
      Morris water maze test was adopted to assess the cognitive function, using laser
      Doppler flowmetry to test changes of regional cerebral blood flow (rCBF); double
      antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) to measure
      proinflammatory cytokines (IL-6, TNF-alpha, and IL-1beta); western blot to test
      the protein expression quantities of proinflammatory cytokines, JAK2, and STAT3;
      and RT-PCR to test JAK2 mRNA and STAT3 mRNA in the hippocampus in each group.
      Results. Compared with the model group, learning and memory abilities and rCBF
      and IL-6 expression of the EA group enhanced markedly; IL-1beta and JAK2
      significantly decreased; TNF-alpha and STAT3 also declined, but the difference
      was not apparent. Conclusion. Our research suggests that EA can improve cognitive
      deficits which may be induced by increasing rCBF and anti-inflammatory effect.

PMID- 28491109
TI  - Retracted: Expression Profiling of Transcriptome and Its Associated Disease Risk
      in Yang Deficiency Constitution of Healthy Subjects.
AB  - [This retracts the article DOI: 10.1155/2016/1493098.].

PMID- 28491110
TI  - Tai-Chi-Chuan Exercise Improves Pulmonary Function and Decreases Exhaled Nitric
      Oxide Level in Both Asthmatic and Nonasthmatic Children and Improves Quality of
      Life in Children with Asthma.
AB  - Tai-Chi-Chuan (TCC) is an exercise of low-to-moderate intensity which is suitable
      for asthmatic patients. The aim of our study is to investigate improvements of
      the lung function, airway inflammation, and quality of life of asthmatic children
      after TCC. Participants included sixty-one elementary school students and they
      were divided into asthmatic (n = 29) and nonasthmatic (n = 32) groups by the
      International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.
      Among them, 20 asthmatic and 18 nonasthmatic children volunteered to participate
      in a 60-minute TCC exercise weekly for 12 weeks. Baseline and postintervention
      assessments included forced expiratory volume in one second (FEV1), forced vital
      capacity (FVC), peak expiratory flow rate (PEFR), fractional exhaled nitric oxide
      (FeNO) level, and Standardised Pediatric Asthma Quality of Life Questionnaire
      (PAQLQ(S)). After intervention, the level of FeNO decreased significantly; PEFR
      and the FEV1/FVC also improved significantly in both asthmatic group and
      nonasthmatic group after TCC. The asthmatic children also had improved quality of
      life after TCC. The results indicated that TCC could improve the pulmonary
      function and decrease airway inflammation in both children with mild asthma and
      those without asthma. It also improves quality of life in mild asthmatic
      children. Nevertheless, further studies are required to determine the effect of
      TCC on children with moderate-to-severe asthma.

PMID- 28491111
TI  - Ficus hispida Bark Extract Prevents Nociception, Inflammation, and CNS
      Stimulation in Experimental Animal Model.
AB  - Background. Ficus hispida is traditionally used in the ailment of pain,
      inflammation, and neurological disorders. The present study set out to evaluate
      the in vivo antinociceptive, anti-inflammatory, and sedative activity of the
      ethanol extract of Ficus hispida bark (EFHB). Methods. The antinociceptive
      activity of EFHB was evaluated by using acetic acid induced writhing, formalin,
      hot plate, and tail immersion methods in Swiss albino mice. Its anti-inflammatory
      activity was assessed by using carrageenan and histamine induced rat paw oedema
      test in Wister rats. The central stimulating activity was studied by using
      pentobarbital induced hypnosis, hole cross, and open field tests in Swiss albino
      mice. Results. EFHB demonstrated antinociceptive activity both centrally and
      peripherally. It showed 62.24% of writhing inhibition. It significantly inhibited
      licking responses in early (59.29%) and late phase (71.61%). It increased the
      reaction time to the thermal stimulus in both hot plate and tail immersion. It
      inhibited the inflammation to the extent of 59.49%. A substantial increase in
      duration of sleep up to 60.80 min and decrease of locomotion up to 21.70 at 400
      mg/kg were also observed. Conclusion. We found significant dose dependent
      antinociceptive, anti-inflammatory, and sedative properties of EFHB in
      experimental animal models.

PMID- 28491112
TI  - Medicinal Plants and Natural Active Compounds for Cancer
      Chemoprevention/Chemotherapy.

PMID- 28491113
TI  - Antioxidant, Anti-Inflammatory, and Analgesic Activities of Agrimonia eupatoria
      L. Infusion.
AB  - Agrimony (Agrimonia eupatoria L.) (Ae) is used in traditional medicine to treat
      inflammatory and oxidative related diseases. Therefore, this study focuses on the
      anti-inflammatory and analgesic potential of Ae infusion (AeI). Phenolic
      compounds characterization was achieved by HPLC-PDA-ESI/MS n . To evaluate
      antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion,
      hydroxyl radical, and SNAP assays were used. In vitro anti-inflammatory activity
      of AeI was investigated in LPS-stimulated macrophages by measuring the NO
      production. In vivo anti-inflammatory activity was validated using the mouse
      carrageenan-induced paw edema model. Peripheral and central analgesic potential
      was evaluated using the acetic acid-induced writhing and hot-plate tests,
      respectively, as well as the formalin assay to assess both activities. The safety
      profile was disclosed in vitro and in vivo, using MTT and hematoxylin assays,
      respectively. Vitexin, quercetin O-galloyl-hexoside, and kaempferol O-acetyl
      hexosyl-rhamnoside were referred to in this species for the first time. AeI and
      mainly AePF (Ae polyphenolic fraction) showed a significant antiradical activity
      against all tested radicals. Both AeI and AePF decreased NO levels in vitro, AePF
      being more active than AeI. In vivo anti-inflammatory and analgesic activities
      were verified for both samples at concentrations devoid of toxicity. Agrimony
      infusion and, mainly, AePF are potential sources of antiradical and anti
      inflammatory polyphenols.

PMID- 28491114
TI  - Optimal Solubility of Diclofenac beta-Cyclodextrin in Combination with Local
      Anaesthetics for Mesotherapy Applications.
AB  - Because of low injection volume, the recently marketed injectable solution of
      diclofenac in complex with beta-cyclodextrin (Akis(r), IBSA Farmaceutici Italia)
      is an ideal candidate for mesotherapy applications. In this study, we
      investigated the solubility of Akis, 25 and 50 mg/kg, in combination with various
      local anaesthetics (lidocaine, mepivacaine, bupivacaine, levobupivacaine, and
      ropivacaine) at different concentrations in aqueous vehicles (normal saline,
      sterile water, or bicarbonate). Final injection mixtures were classified as
      limpid, turbid, or milky at visual analysis under standardized conditions. We
      found that (i) the use of sterile water for injections or normal saline as
      vehicles to dilute Akis in combination with whatever local anaesthetic normally
      results in milky solutions and therefore is not recommended; (ii) using
      bicarbonate, optimal solubility was obtained combining Akis with lidocaine, both
      1 and 2%, or mepivacaine, both 1 and 2%, whereas solutions were turbid in
      combination with bupivacaine, levobupivacaine, or ropivacaine. Thus, we recommend
      that Akis is used in combination with lidocaine or mepivacaine in a bicarbonate
      vehicle.

PMID- 28491115
TI  - Therapeutic Risk and Benefits of Concomitantly Using Herbal Medicines and
      Conventional Medicines: From the Perspectives of Evidence Based on Randomized
      Controlled Trials and Clinical Risk Management.
AB  - Despite increased awareness of the potential of herb-drug interactions (HDIs),
      the lack of rigorous clinical evidence regarding the significance provides a
      challenge for clinicians and consumers to make rational decisions about the safe
      combination of herbal and conventional medicines. This review addressed HDIs
      based on evidence from randomized controlled trials (RCTs). Literature was
      identified by performing a PubMed search till January 2017. Risk description and
      clinical risk management were described. Among 74 finally included RCTs, 17 RCTs
      (22.97%) simply addressed pharmacodynamic HDIs. Fifty-seven RCTs (77.03%)
      investigated pharmacokinetic HDIs and twenty-eight of them showed potential or
      actual clinical relevance. The extent of an HDI may be associated with the
      factors such as pharmacogenomics, dose of active ingredients in herbs, time
      course of interaction, characteristics of the object drugs (e.g., administration
      routes and pharmacokinetic profiles), modification of herbal prescription
      compositions, and coexistence of inducers and inhibitors. Clinical professionals
      should enhance risk management on HDIs such as increasing awareness of potential
      changes in therapeutic risk and benefits, inquiring patients about all currently
      used conventional medicines and herbal medicines and supplements, automatically
      detecting highly substantial significant HDI by computerized reminder system,
      selecting the alternatives, adjusting dose, reviewing the appropriateness of
      physician orders, educating patients to monitor for drug-interaction symptoms,
      and paying attention to follow-up visit and consultation.

PMID- 28491116
TI  - A Randomized Clinical Trial Comparing the Effectiveness of Electroacupuncture
      versus Medium-Frequency Electrotherapy for Discogenic Sciatica.
AB  - Objective. To investigate the short- and long-term effects of electroacupuncture
      (EA) compared with medium-frequency electrotherapy (MFE) on chronic discogenic
      sciatica. Methods. One hundred participants were randomized into two groups to
      receive EA (n = 50) or MFE (n = 50) for 4 weeks. A 28-week follow-up of the two
      groups was performed. The primary outcome measure was the average leg pain
      intensity. The secondary outcome measures were the low back pain intensity,
      Oswestry Disability Index (ODI), patient global impression (PGI), drug use
      frequency, and EA acceptance. Results. The mean changes in the average leg pain
      numerical rating scale (NRS) scores were 2.30 (1.86-2.57) and 1.06 (0.62-1.51) in
      the EA and MFE groups at week 4, respectively. The difference was significant (P
      < 0.001). The long-term follow-up resulted in significant differences. The
      average leg pain NRS scores decreased by 2.12 (1.70-2.53) and 0.36 (-0.05-0.78)
      from baseline in the EA and MFE groups, respectively, at week 28. However, low
      back pain intensity and PGI did not differ significantly at week 4. No serious
      adverse events occurred. Conclusions. EA showed greater short-term and long-term
      benefits for chronic discogenic sciatica than MFE, and the effect of EA was
      superior to that of MFE. The study findings warrant verification. This trial was
      registered under identifier ChiCTR-IPR-15006370.

PMID- 28491117
TI  - Herpes virus seroepidemiology in the adult Swedish population.
AB  - BACKGROUND: Herpes viruses establish a life-long latency and can cause symptoms
      during both first-time infection and later reactivation. The aim of the present
      study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1),
      Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV)
      and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years
      of age). METHODS: Presence of antibodies against the respective viruses in serum
      from individuals in the Betula study was determined with an enzyme-linked
      immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean
      age at inclusion 62.7 +/- 14.4 years) collected 2003-2005 were analyzed for the
      five HHVs mentioned above. In addition, samples including follow-up samples
      collected 1988-2010 from 3,444 persons were analyzed for HSV. RESULTS: Prevalence
      of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus
      infections were more common among women (p = 0.010) and a lower age-adjusted HSV
      seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence
      of HSV infection was estimated at 14.0/1000. CONCLUSION: Women are more often
      seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was
      lower in later birth cohorts indicating a decreasing childhood and adolescent
      risk of infection.

PMID- 28491118
TI  - The head morphology of Pyrrhosoma nymphula larvae (Odonata: Zygoptera) focusing
      on functional aspects of the mouthparts.
AB  - BACKGROUND: The understanding of concerted movements and its underlying
      biomechanics is often complex and elusive. Functional principles and hypothetical
      functions of these complex movements can provide a solid basis for biomechanical
      experiments and modelling. Here a description of the cephalic anatomy of
      Pyrrhosoma nymphula (Zygoptera, Coenagrionidae) focusing on functional aspects of
      the mouthparts using micro computed tomography (MUCT) is presented. RESULTS: We
      compared six different instars of the damselfly P. nymphula as well as one instar
      of the dragonfly Aeshna cyanea and Epiophlebia superstes each. In total 42 head
      muscles were described with only minor differences of the attachment points
      between the examined species and the absence of antennal muscle M.
      scapopedicellaris medialis (0an7) in Epiophlebia as a probable apomorphy of this
      group. Furthermore, the ontogenetic differences between the six larval instars
      are minor; the only considerable finding is the change of M. submentopraementalis
      (0la8), which is dichotomous in the early instars (I1,I2 and I3) with a second
      point of origin at the postero-lateral base of the submentum. This dichotomy is
      not present in any of the older instars studied (I6, middle-late and pen
      ultimate). CONCLUSION: However, the main focus of the study herein, is to use
      these detailed morphological descriptions as basis for hypothetic functional
      models of the odonatan mouthparts. We present blueprint like description of the
      mouthparts and their musculature, highlighting the caused direction of motion for
      every single muscle. This data will help to elucidate the complex concerted
      movements of the mouthparts and will contribute to the understanding of its
      biomechanics not in Odonata only.

PMID- 28491119
TI  - Association of adipokines with blood pressure, arterial elasticity and cardiac
      markers in dialysis patients: cross-sectional analysis of baseline data from a
      cohort study.
AB  - BACKGROUND: Adipokines are a set of cytokines secreted by white adipose tissue
      that have been suggested to be involved in the development of cardiovascular
      diseases. We aimed to evaluate the cross-sectional associations of a panel of
      representative adipokines with cardiovascular measures in a cohort of
      hemodialysis patients. METHODS: We measured plasma adiponectin, resistin,
      plasminogen activator inhibitor-1 (PAI-1), leptin, monocyte chemotactic protein 1
      (MCP-1) and adipsin levels in 366 dialysis patients and 60 healthy controls. The
      associations of these adipokines with systolic blood pressure (assessed by
      ambulatory blood pressure monitoring), pulse wave velocity (PWV) and cardiac
      markers (BNP, NT-proBNP, Troponin I, Troponin T) in these patients were
      determined by general linear models with stepwise adjustment for covariates.
      RESULTS: In unadjusted comparison with controls, dialysis patients showed
      increased adiponectin, resistin, MCP-1 and adipsin levels, decreased PAI-1
      concentrations (all p <0.001) and similar leptin levels (p = 0.82). On adjustment
      for body mass index and diabetes, however, the PAI-1 level was comparable between
      group (p = 0.06), whereas leptin levels became significantly higher in the
      patients(p <0.001). Higher adiponectin, lower PAI-1 and leptin levels were
      associated with higher systolic blood pressure, even after extensive adjustment
      (all p <= 0.01). Adiponectin was also consistently and inversely associated with
      PWV in fully adjusted models (p = 0.003). Resistin, PAI-1, leptin and adipsin
      showed negative associations with one or more circulating cardiac markers (all p
      <= 0.02). CONCLUSIONS: We found significant associations between adipokines and
      cardiovascular measures. Our data suggest the possible involvement of adipokines
      in cardiovascular modulation in dialysis patients.

PMID- 28491120
TI  - Microscopy of Physcomitrella patens sperm cells.
AB  - BACKGROUND: Archegoniates (bryophytes, ferns and gymnosperms), such as the moss
      Physcomitrella patens, possess freely motile sperm cells (spermatozoids) which
      reach the egg cell via surface water. Although these motile flagellated sperm
      cells are a traditional botanical subject, they have not been thoroughly analysed
      in the flagship non-seed plant model species P. patens. Protocols are required to
      determine the behaviour of wild type sperms as a prerequisite for future research
      such as the characterization of mutants or factors that influence sperm number,
      morphology, viability and motility. RESULTS: Here, we present protocols for the
      observation of fixed, as well as live sperms utilizing a standard microscope at
      intermediate magnifications. Fixed samples can be used for the fast assessment of
      sperm number and morphology. To determine functionality, the observation of live
      sperms is required. Protocols for determining both sperm motility and viability
      are provided, allowing both parameters to be distinguished. CONCLUSIONS: These
      step-by-step protocols are particularly useful for researchers so far not
      familiar with the analysis of motile gametes and are meant to aid the
      establishment and improvement of these analyses in order to stimulate research on
      spermatogenesis in the moss model species P. patens.

PMID- 28491121
TI  - Development of a new heat tolerance assay system for rice spikelet sterility.
AB  - BACKGROUND: Reduction in rice yield caused by high temperature-induced spikelet
      sterility has been a serious concern in rice production. To date, several
      screening methods have been used, although their reproducibility is sometimes
      poor due to artifacts mainly caused by varietal differences in heading dates and
      panicle heights (i.e., the distance from the lamps). METHODS: We have developed a
      novel assay system for heat-induced spikelet sterility by using artificial rice
      paddies in phytotrons to conduct a highly reproducible assay throughout a year.
      Plants restricted to the main culm were treated under a series of heat
      conditions, and height uniformity of each plant was ensured by using height
      adjustable pots. RESULTS: Results suggested that a 3-day heat treatment of 35 
      degrees C-day/29  degrees C-night cycles was the most suitable condition. Under
      the treatment, two distinct groups were identified among nine heat tolerant
      cultivars, with no varietal difference in panicle temperature, indicating that
      the system is capable of eliminating the varietal difference in panicle
      temperature. CONCLUSIONS: It is concluded that the assay system would be a
      powerful tool for selecting heat tolerant varieties, as well as the analysis of
      genetic factors from various cultivars, eliminating potential artifacts.

PMID- 28491123
TI  - Editorial.

PMID- 28491122
TI  - In situ measurement of Scots pine needle PRI.
AB  - BACKGROUND: The Photochemical Reflectance Index (PRI) calculated from narrow-band
      spectral reflectance data is a vegetation index which is increasingly used as an
      indicator of photosynthetic activity. The leaf-level link between the status of
      photosynthetic apparatus and PRI has been robustly established under controlled
      light conditions. However, when a whole canopy is measured instantaneously, the
      PRI signal is heavily modified by vegetation structure and local variations in
      incident light conditions. To apply PRI for monitoring the photosynthesis of
      whole canopies under natural conditions, these large-scale measurements need to
      be validated against simultaneous leaf PRI. Unfortunately, PRI changes
      dynamically with incident light and has a large natural variation. No generally
      accepted procedure exists today for determining the PRI of canopy elements in
      situ. RESULTS: We present a successful procedure for in situ measurements of
      needle PRI. We describe, characterize and test an optical measurement protocol
      and demonstrate its applicability in field conditions. The measurement apparatus
      consisted of a light source, needle clip, spectroradiometer and a controlling
      computer. The light level inside the clip was approximately two-thirds of that on
      sunlit needle surfaces at midday. During each measurement the needle was inserted
      into the clip for approximately 5 s. We found no near-instantaneous changes (sub
      second scale jumps) in PRI during the measurements. The time constants for PRI
      variation in light to full shade acclimations were approximately 10 s. The
      procedure was successfully applied to monitor the greening-up of Scots pine
      trees. We detected both facultative (diurnal) PRI changes of 0.02 (unitless) and
      constitutive (seasonal) variations of 0.1. In order to reliably detect the
      facultative PRI change of 0.02, 20 needles need to be sampled from both sunlit
      and shaded locations. CONCLUSIONS: We established a robust procedure for
      irradiance-dependent leaf (needle) PRI measurements, facilitating empirical
      scaling of PRI from leaf (needle) to full canopy level and the application of PRI
      to monitoring the changes in highly structured vegetation. The measured time
      constants, and facultative and constitutive PRI variations support the use of an
      artificial light for in situ PRI measurements at leaf (needle) level.

PMID- 28491124
TI  - Strategies to reduce the global burden of direct maternal deaths.
AB  - The leading direct causes of the estimated 196 maternal deaths per 100,000 live
      births globally are postpartum haemorrhage, the hypertensive disorders of
      pregnancy, obstructed labour, unsafe abortion and obstetric sepsis. Of the
      Sustainable Development Goals, one (Sustainable Development Goal 3.1)
      specifically addresses maternal mortality; by 2030, the goal is to reduce the
      global maternal mortality ratio to less than 70 per 100,000 live births. Eleven
      other Sustainable Development Goals provide opportunities to intervene.
      Unapologetically, this review focusses the reader's attention on health advocacy
      and its central role in altering the risks that many of the world's women face
      from direct obstetric causes of mortality. Hard work to alter social determinants
      of health and health outcomes remains. That work needs to start today to improve
      the health and social equality of today's girls who will be the women delivering
      their babies in 2030.

PMID- 28491126
TI  - Developing obstetric medicine training in Latin America.
AB  - Maternal mortality is an important indicator of health in populations around the
      world. The distribution of maternal mortality ratio globally shows that middle-
      and low-income countries have ~99% of the mortality burden. Most countries of
      Latin America are considered to be middle- or low-income countries, as well as
      areas of major inequities among the different social classes. Medical problems in
      pregnancy remain an important cause of morbidity and mortality in this region.
      Previous data indicate the need for a call to action for adequate diagnosis and
      care of medical diseases in obstetric care. The impact of nonobstetric and
      medical pathologies on maternal mortality in Latin America is largely unknown. In
      Latin America, two educational initiatives have been proposed to improve skills
      in maternity care. The Advanced Life Support in Obstetrics (ALSO(r)) was first
      started to address obstetric emergencies, and subsequently adapted for low-middle
      income country settings as the Global ALSO(r). In parallel, the Latin American
      obstetric anesthesia community has progressively focused on improvement of
      several intrapartum/intraoperative issues, which has secondarily taken them to
      embrace the obstetric medicine area on interest and join the former initiatives.
      In the present review, we summarize the available data regarding medical
      morbidity and mortality in pregnancy in Latin America, as well as the challenges,
      achievements, issues, initiatives, and future directions encouraging maternal
      health educators, health care trainers, and physicians in middle- and low-income
      countries, such as many Latin American ones, to improve and/or change attitudes,
      if needed, on current clinical practice.

PMID- 28491125
TI  - Indirect maternal deaths: UK and global perspectives.
AB  - Indirect maternal deaths outnumber direct deaths due to obstetric causes in many
      high-income countries, and there has been a significant increase in the
      proportion of maternal deaths due to indirect medical causes in low- to middle
      income countries. This review presents a detailed analysis of indirect maternal
      deaths in the UK and a perspective on the causes and trends in indirect maternal
      deaths and issues related to care in low- to middle-income countries. There has
      been no significant decrease in the rate of indirect maternal deaths in the UK
      since 2003. In 2011-2013, 68% of all maternal deaths were due to indirect causes,
      and cardiac disease was the single largest cause. The major issues identified in
      care of women who died from an indirect cause was a lack of clarity about which
      medical professional should take responsibility for care and overall management.
      Under-reporting and misclassification result in underestimation of the rate of
      indirect maternal deaths in low- to middle-income countries. Causes of indirect
      death include a range of communicable diseases, non-communicable diseases and
      nutritional disorders. There has been evidence of a shift in incidence from
      direct to indirect maternal deaths in many low- to middle-income countries due to
      an increase in non-communicable diseases among women in the reproductive age. The
      gaps in care identified include poor access to health services, lack of
      healthcare providers, delay in diagnosis or misdiagnosis and inadequate follow-up
      during the postnatal period. Irrespective of the significant gains made in
      reducing maternal mortality in many countries worldwide, there is evidence of a
      steady increase in the rate of indirect deaths due to pre-existing medical
      conditions. This heightens the need for research to generate evidence about the
      risk factors, management and outcomes of specific medical comorbidities during
      pregnancy in order to provide appropriate evidence-based multidisciplinary care
      across the entire pathway: pre-pregnancy, during pregnancy and delivery, and
      postpartum.

PMID- 28491127
TI  - Global initiatives in maternal and newborn health.
AB  - In 2015, 17 sustainable development goals were established for 2030. These global
      goals aim to ensure healthy lives and promote wellbeing for all. In support of
      the sustainable development goals, the World Health Organization proposed a new
      global strategy for women's, children's, and adolescents' health in 2016 with
      three overarching objectives: to survive, to thrive, and to transform. We are now
      globally seeking not only to end preventable deaths but also to ensure health and
      wellbeing, and expand enabling environments. This strategy builds on several
      prior initiatives in maternal and newborn health, such as the Every Woman, Every
      Child initiative, and the strategy to end preventable maternal mortality and
      implementation of an action plan to end preventable newborn death. This
      confluence of initiatives, strategies, and novel financing mechanisms under the
      umbrella of the sustainable development goals and the global strategy pave the
      way for a global agenda in which securing women's health is critical.

PMID- 28491128
TI  - Non-communicable diseases during pregnancy in low and middle income countries.
AB  - Apart from the risks of obstetric complications like haemorrhage and eclampsia, a
      large number of medical conditions affect pregnancy and result in adverse
      outcomes for both the mother and offspring. Non-communicable diseases in
      pregnancy are becoming increasingly important in contributing to death and poor
      health. Changes in the patterns and distribution of these conditions mean that we
      need new perspectives and ways of dealing with these challenges for the future.
      This article reviews the burden of ill-health due to non-communicable diseases
      during pregnancy in low and middle income countries and presents some paradigms
      relevant to public health and health system needs of the future.

PMID- 28491129
TI  - The XXI International Society of Hypertension in Pregnancy meeting, Sao Paulo,
      Brazil - A global health perspective.
AB  - The 21st International Society of Hypertension in Pregnancy (ISSHP) meeting was
      held in Sao Paulo, Brazil from 23 to 26 October 2016. The discourse at this
      Congress brought global maternal health into the foray among basic science and
      clinical research. In concordance with the United Nations sustainable development
      goals which warrant an integrated view to health with investments in adolescence
      and childhood, the research at Congress focussed on a 'life course' approach to
      maternal health - examining intergenerational effects of maternal obesity and
      hypertension on the behavioral and physical developments of infants. Bringing in
      research from the Global South highlighted inequities in treatment and management
      of women with hypertensive disorders of pregnancy, in addition to the challenges
      in adoption of recommendations generated in Global North. The evidence shared can
      serve as platform for further discourse on global maternal health and in
      generating accountability to close the 'evidence to policy' gap.

PMID- 28491130
TI  - Advocacy is essential to supporting women with pre-eclampsia.
AB  - Advocacy has a critical role in advancing the maternal health agenda. Patient
      advocacy groups can hold governments and other stakeholders accountable and
      ensure that commitments are translated into concrete action. This article
      highlights the advocacy efforts of the Preeclampsia Foundation, a patient
      advocacy organisation that aims to improve the diagnosis, management, and
      prevention of pre-eclampsia through research and improved healthcare practices. A
      number of challenges continue to face maternal health advocacy especially in low-
      and middle-income countries. Future directions include developing a strategic
      focus for advocacy, effectively engaging citizens to build a culture of
      accountability, and monitoring and evaluation of advocacy efforts.

PMID- 28491131
TI  - Obstetric medical care in the United States of America.
AB  - The current models of obstetric medical care utilized in the United States, how
      those models fit in with the overall care system, and ways to increase the role
      of obstetric internists will be reviewed.

PMID- 28491132
TI  - Obstetric medical care and training in the United Kingdom.
AB  - The UK confidential enquiry into maternal deaths identified poor management of
      medical problems in pregnancy to be a contributory factor to a large proportion
      of indirect maternal deaths. Maternal (obstetric) medicine is an exciting
      subspecialty that encompasses caring for both women with pre-existing medical
      conditions who become pregnant, as well as those who develop medical conditions
      in pregnancy. Obstetrics and gynaecology trainees have some exposure to maternal
      medicine through their core curriculum and can then complete an advanced training
      skills module, subspecialise in maternal-fetal medicine or take time out to
      complete the Royal College of Physicians membership examination. Physician
      training has limited exposure to medical problems in pregnancy and has therefore
      prompted expansion of the obstetric physician role to ensure physicians with
      adequate expertise attend joint physician-obstetrician clinics. This article
      describes the role of an obstetric physician in the UK and the different career
      pathways available to physicians and obstetricians interested in maternal
      medicine.

PMID- 28491133
TI  - The way forward.
AB  - Improving maternal health and reducing maternal morbidity and mortality into the
      future will require a range of health-related and non-health-related strategies.
      The latter include education for women, better communication, access to transport
      and technology and cultural change. The role of obstetric medicine practice,
      research and education in achieving these objectives is discussed in this
      article. We need to recognise that it will require improvements in health
      provision and access to achieve our goal of safer childbirth for women and babies
      throughout the world.

PMID- 28491134
TI  - Traditional practices and adverse pregnancy outcomes in migrant women.
AB  - Traditional practices during pregnancy may lead to adverse outcomes in migrant
      women. Very little is known regarding the efficacy or safety of many cultural
      practices during pregnancy, and research is required to address this deficiency
      in knowledge. Greater awareness of traditional practices by health professionals
      may result in improved pregnancy outcomes in migrant women.

PMID- 28491135
TI  - Highlights from the 15th St Gallen International Breast Cancer Conference 15-18
      March, 2017, Vienna: tailored treatments for patients with early breast cancer.
AB  - The 15th St Gallen International Breast Cancer Conference was held in Vienna for
      the second time, from 15th-18th March 2017. 4000 people from 105 countries all
      over the world were invited to take part in the event. The real highlight of the
      conference was the last day with the International Consensus Session which was
      chaired by around 50 experts on breast cancer worldwide. With reference to data
      from scientific research, the consensus panel tried to offer guidelines for the
      management of breast cancer with the aim of providing patients with optimal
      treatment. The topics covered focused on the treatment of breast cancer,
      consideration of surgery, radiotherapy, neo-adjuvant, and adjuvant systemic
      therapy for breast cancer, as well as genetics and prevention of breast cancer.
      In particular, in terms of precision medicine, an important topic of the
      conference was 'is it possible to think that it could become routine in clinical
      practice to use immunotherapy and targeted therapy based on genetic signatures?'
      In view of personalised therapy, it is important to take into consideration
      women's treatment preferences. It is also important not only to offer guidelines
      which help breast cancer experts all over the world to choose the proper
      treatment for women with breast cancer but also to discuss the pros and cons of
      the therapy with the patient. This allows for a better understanding of the
      disease. 'From the maximum tolerable to the minimum effective treatment: it is
      essential to escalate treatment when necessary and to de-escalate when
      unnecessary'. These few words could summarise the meaning of the 15th St Gallen
      International Breast Cancer Conference. Prof Martine Piccart-Gebhart was awarded
      with the St Gallen International Breast Cancer Award 2017 for her fundamental
      clinical research contribution and Prof Giuseppe Curigliano with the Umberto
      Veronesi Memorial Award which aims to recognise a physician's leading role in
      advancing the science and care of breast cancer patients. Curigliano, in his
      lecture, spoke about the revolutionary immunotherapy in the clinical management
      of breast cancer (BC). For the development of these therapies, it is necessary to
      identify the genetic determinants of BC immune phenotypes in which The Cancer
      Genome Atlas (TCGA) has contributed towards this. For example, the T helper (Th
      1) phenotype (ICR4), which also exhibits upregulation of immune-regulatory
      transcripts (eg. PDL1, PD1, FOXP3, IDO1, and CTLA4), was associated with
      prolonged patients' survival. Chromosome segment 4q21, which includes genes
      encoding the Th-1 chemokines CXCL9-11, was significantly amplified only in the
      immune favourable phenotype (ICR4). The mutation and neo-antigen load
      progressively decreased from ICR4 to ICR1 but could not explain immune phenotypic
      differences. Mutations of TP53 were enriched in the immune favourable phenotype
      (ICR4). Instead, the presence of MAP3K1 and MAP2K4 mutations were closely
      associated with an immune unfavourable phenotype (ICR1). Using both the TCGA and
      the validation dataset, the degree of MAPK deregulation segregates BC according
      to their immune disposition. These findings suggest that mutational-driven
      deregulation of MAPK pathways is linked to the negative regulation of
      intratumoural immune response in BC. The main themes of this congress were: 1)
      Surgery of the primary tumour and margins; 2) Surgery of the axilla; 3)
      Radiotherapy: hypofractionated, 'boost' to tumour bed, partial breast, regional
      node, after mastectomy, advanced technology; 4) Pathology: subtypes, TILs; 5)
      Multi-gene signatures and therapy; 6) Endocrine therapy: pre- and post-menopausal
      and duration; 7) Chemotherapy: subtypes, stages; 8) Anti-HER-2 therapy; 9) Neo
      adjuvant therapy; 10) Adjuvant bisphosponates; 11) Adjuvant diet and exercise.

PMID- 28491136
TI  - Applications of microalgal biofilms for wastewater treatment and bioenergy
      production.
AB  - BACKGROUND: Microalgae have shown clear advantages for the production of biofuels
      compared with energy crops. Apart from their high growth rates and substantial
      lipid/triacylglycerol yields, microalgae can grow in wastewaters (animal,
      municipal and mining wastewaters) efficiently removing their primary nutrients
      (C, N, and P), heavy metals and micropollutants, and they do not compete with
      crops for arable lands. However, fundamental barriers to the industrial
      application of microalgae for biofuel production still include high costs of
      removing the algae from the water and the water from the algae which can account
      for up to 30-40% of the total cost of biodiesel production. Algal biofilms are
      becoming increasingly popular as a strategy for the concentration of microalgae,
      making harvesting/dewatering easier and cheaper. RESULTS: We have isolated and
      characterized a number of natural microalgal biofilms from freshwater, saline
      lakes and marine habitats. Structurally, these biofilms represent complex
      consortia of unicellular and multicellular, photosynthetic and heterotrophic
      inhabitants, such as cyanobacteria, microalgae, diatoms, bacteria, and fungi.
      Biofilm #52 was used as feedstock for bioenergy production. Dark fermentation of
      its biomass by Enterobacter cloacae DT-1 led to the production of 2.4 mol of
      H2/mol of reduced sugar. The levels and compositions of saturated, monosaturated
      and polyunsaturated fatty acids in Biofilm #52 were target-wise modified through
      the promotion of the growth of selected individual photosynthetic inhabitants.
      Photosynthetic components isolated from different biofilms were used for
      tailoring of novel biofilms designed for (i) treatment of specific types of
      wastewaters, such as reverse osmosis concentrate, (ii) compositions of total
      fatty acids with a new degree of unsaturation and (iii) bio-flocculation and
      concentration of commercial microalgal cells. Treatment of different types of
      wastewaters with biofilms showed a reduction in the concentrations of key
      nutrients, such as phosphates, ammonia, nitrates, selenium and heavy metals.
      CONCLUSIONS: This multidisciplinary study showed the new potential of natural
      biofilms, their individual photosynthetic inhabitants and assembled new
      algal/cyanobacterial biofilms as the next generation of bioenergy feedstocks
      which can grow using wastewaters as a cheap source of key nutrients.

PMID- 28491137
TI  - Boosting LPMO-driven lignocellulose degradation by polyphenol oxidase-activated
      lignin building blocks.
AB  - BACKGROUND: Many fungi boost the deconstruction of lignocellulosic plant biomass
      via oxidation using lytic polysaccharide monooxygenases (LPMOs). The application
      of LPMOs is expected to contribute to ecologically friendly conversion of biomass
      into fuels and chemicals. Moreover, applications of LPMO-modified cellulose-based
      products may be envisaged within the food or material industry. RESULTS: Here, we
      show an up to 75-fold improvement in LPMO-driven cellulose degradation using
      polyphenol oxidase-activated lignin building blocks. This concerted enzymatic
      process involves the initial conversion of monophenols into diphenols by the
      polyphenol oxidase MtPPO7 from Myceliophthora thermophila C1 and the subsequent
      oxidation of cellulose by MtLPMO9B. Interestingly, MtPPO7 shows preference
      towards lignin-derived methoxylated monophenols. Sequence analysis of genomes of
      336 Ascomycota and 208 Basidiomycota reveals a high correlation between MtPPO7
      and AA9 LPMO genes. CONCLUSIONS: The activity towards methoxylated phenolic
      compounds distinguishes MtPPO7 from well-known PPOs, such as tyrosinases, and
      ensures that MtPPO7 is an excellent redox partner of LPMOs. The correlation
      between MtPPO7 and AA9 LPMO genes is indicative for the importance of the coupled
      action of different monooxygenases in the concerted degradation of
      lignocellulosic biomass. These results will contribute to a better understanding
      in both lignin deconstruction and enzymatic lignocellulose oxidation and
      potentially improve the exploration of eco-friendly routes for biomass
      utilization in a circular economy.

PMID- 28491138
TI  - Clinicohematological and cytogenetic profile of myelodysplastic syndromes in
      Pakistan-compare and contrast.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) are clonal stem cell disorders
      exhibiting cytopenias, ineffective hematopoiesis and morphological dysplasia.
      Bone marrow cytogenetics, inspite of being incorporated as mandatory tool in
      diagnosis are done less frequently due to limited availability of this technique
      in Pakistan. The aim of the study was to study baseline clinicohematological and
      cytogenetic characteristics of patients presenting with de novo MDS. RESULTS: A
      retrospective cross sectional study was done at National Institute of Blood
      Diseases and Bone Marrow Transplantation, Karachi, Pakistan from 2010 to 2016.
      Total of 177 patients were included in the study having median age 51 years and
      male to female ratio of 3:1. Pancytopenia was observed in 80 (45%) patients and
      bicytopenia in 74 (42%). Mean Hb% was 7.8 +/- 2.18 g/dl, total leukocyte count
      (TLC) 8.8 +/- 13.6 * 109/l, platelet count was 82 +/- 95.7 * 109/l. Of total 170
      (96%) were transfusion dependent. Refractory cytopenias with multilineage
      dysplasia (RCMD) was the most common world health organization (WHO) category.
      Karyotype was done in 98 (55%) patients out of which 44 (45%) had abnormal
      karyotype, complex karyotype (CK) was most commonly observed in 12 (12.2%)
      followed by monosomy 7 in 7 (7.1%). CONCLUSIONS: We found younger median age at
      diagnosis, higher mean TLC and no significant history of recurrent infections. CK
      and monosomy 7 carry bad prognostic implications and early disease transformation
      to acute myeloid leukemia (AML). Monosomy 7 being associated with bad overall
      survival, such patients must be identified early with close clinical follow up
      and offered stem cell transplant. This is the largest cohort of patients of MDS
      evaluated for baseline clinical and cytogenetic characteristics in our country.

PMID- 28491139
TI  - Traction using a clip-with-line is a preferred method for trainees in performing
      esophageal endoscopic submucosal dissection: an animal model study.
AB  - BACKGROUND: The optimal operative process of esophageal endoscopic submucosal
      dissection (ESD), especially for the beginners, is not established. In this
      study, the clip-with-line method, the tunneling method and the conventional
      method for esophageal ESD were compared in a training course on live pigs.
      METHODS: 15 trainee endoscopists were randomized into three groups, the clip-with
      line method group, the tunneling method group, and the conventional method group.
      Each trainee performed four esophageal ESDs on live pigs with one of the
      specified methods, assisted by a senior endoscopist. The procedural time and
      speed, the en bloc resection rates, adverse events, and self-completion rates
      were recorded, and learning curves were drawn. RESULTS: The procedural time in
      the clip-with-line group was significantly shorter than those in the tunneling
      and the conventional method group (47.4 +/- 9.0 min versus 67.0 +/- 15.1 min and
      67.0 +/- 11.8 min, p = 0.000). The clip-with-line method had the lowest rates of
      perforation and muscle layer injury among the three methods. The en bloc
      resection rates and self-completion rates were similar among the three groups.
      Learning curves analysis showed the clip-with-line method was the easiest one for
      the trainees to master. CONCLUSIONS: The clip-with-line method shortened
      procedural time for trainees, and was associated with lower rates of adverse
      events. This method is preferred for endoscopists in their learning periods for
      esophageal ESD.

PMID- 28491140
TI  - Tryptase mast cell density, protease-activated receptor-2 microvascular density,
      and classical microvascular density evaluation in gastric cancer patients
      undergoing surgery: possible translational relevance.
AB  - BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several
      proangiogenic cytokines stored in their cytoplasm. In particular, MCs can release
      tryptase, a potent in vivo and in vitro proangiogenic factor via protease
      activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase
      (MAPK) phosphorylation. Nevertheless, no data are available concerning the
      relationship among tryptase MC density (TMCD), endothelial cells (ECs) positive
      to PAR-2 microvascular density (PAR-2-MVD) and classical MVD (C-MVD) in gastric
      cancer (GC) angiogenesis. METHODS: In this study, we analyzed the correlation of
      TMCD, PAR-2-MVD, C-MVD with each other and with the main clinicopathological
      features in GC patients who underwent surgery. A series of 77 GC patients with
      stage T2-3N2-3M0 (classified by the American Joint Committee on Cancer for
      Gastric Cancer, 7th edition) were selected and then underwent surgery. RESULTS:
      Tumour tissue samples were evaluated by mean of immunohistochemistry and image
      analysis methods in terms of numbers of TMCD, PAR-2-MVD and C-MVD. A significant
      correlation between the TMCD, PAR-2-MVD and C-MVD groups with each other was
      found by Pearson t-test analysis (r ranged from 0.64 to 0.76; p value ranged from
      0.02 to 0.03). There was no other significant correlation between the above
      parameters and clinicopathological features. CONCLUSIONS: Our in vivo preliminary
      data suggest that TMCD and PAR-2-MVD may play a role in GC angiogenesis and they
      could be further evaluated as a target of antiangiogenic therapy.

PMID- 28491141
TI  - Universal molecular screening does not effectively detect Lynch syndrome in
      clinical practice.
AB  - BACKGROUND: Lynch syndrome (LS) due to an inherited damaging mutation in mismatch
      repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC).
      Molecular testing using immunohistochemistry (IHC) for MMR proteins is a
      recommended screening tool to identify LS in incident CRC. This study assessed
      outcomes of population-based routine molecular screening for diagnosis of LS in a
      regional center. METHODS: We conducted a prospective, consecutive case series
      study of universal IHC testing on cases of resected CRC from September 2004
      December 2013. Referred cases with abnormal IHC results that attended a familial
      cancer clinic were assessed according to modified Bethesda criteria (until 2009)
      or molecular criteria (from 2009). RESULTS: 1612 individuals underwent resection
      for CRC in the study period and had MMR testing by IHC. Of these, 274 cases
      (16.9%) exhibited loss of expression of MMR genes. The mean age at CRC diagnosis
      was 68.1 years (+/- standard deviation 12.7) and the mean age of those with an
      IHC abnormality was 71.6 (+/- 11.8). A total of 82 (29.9%) patients with an
      abnormal result were seen in a subspecialty familial cancer clinic. Patients aged
      under 50 (p = 0.009) and those with loss of MSH6 staining (p = 0.027) were more
      likely to be referred and to attend. After germ-line sequencing, 0.6% (10 of 82)
      were identified as having a clinically significant abnormality. A further eight
      probands with pathogenic germ-line mutations were identified from other referrals
      to the service over the same time period. CONCLUSIONS: While technically
      accurate, the yield of 'universal' IHC in detecting new Lynch probands is limited
      by real-world factors that reduce referrals and genetic testing. We propose an
      alternative approach for universal, incident case detection of Lynch syndrome
      with 'one-stop' MMR testing and sequencing.

PMID- 28491142
TI  - Current challenges in the treatment of severe Clostridium difficile infection:
      early treatment potential of fecal microbiota transplantation.
AB  - Fecal microbiota transplantation (FMT) is a very effective treatment for
      recurrent Clostridium difficile infection (CDI). Less is known about the
      application of FMT as a curative treatment of severe or complicated CDI. In this
      review, we present and discuss evidence supporting the curative use of FMT in
      severe or complicated CDI. We performed a literature search in PubMed and Embase
      for studies on the curative use of FMT in severe or complicated CDI. In addition,
      we describe a patient with severe CDI not responding to initial antibiotic
      treatment, who was successfully treated with curative FMT. We found 23 reports
      (12 case reports; 11 case series) about FMT as treatment for severe or
      complicated CDI. The patients described all had severe or complicated CDI, did
      not respond to conventional CDI antibiotic treatment and received FMT as last
      resort treatment. Patients were treated with (sequential) FMT, whether or not
      followed by additional antibiotic treatment for CDI. FMT, with or without
      additional antibiotic CDI treatment, appears to be a promising curative treatment
      option in patients with severe and complicated CDI, or only complicated CDI, who
      do not respond sufficiently to conventional antibiotic treatment. Treatment with
      FMT should be considered in these patients before proceeding to emergency bowel
      surgery.

PMID- 28491144
TI  - Clinical effectiveness and toxicity of second-line irinotecan in advanced gastric
      and gastroesophageal junction adenocarcinoma: a single-center observational
      study.
AB  - BACKGROUND: Randomized clinical trials showed improved overall survival (OS) of
      advanced gastroesophageal adenocarcinoma (GEA) patients treated with second-line
      taxane or irinotecan. However, most data on irinotecan efficacy in this setting
      come from large Asian trials. We retrospectively analyzed clinical effectiveness
      and toxicity of irinotecan in a cohort of patients with advanced GEA treated in
      our department. METHODS: Advanced GEA patients who received at least one cycle of
      second-line irinotecan were eligible for inclusion. Irinotecan was administered
      every 3 weeks at an initial dose of 250 mg/m2 of body surface area with
      subsequent gradual (every 50 mg/m2) dose escalation up to 350 mg/m2, in the case
      of good treatment tolerance. OS was estimated using the Kaplan-Meier method. A
      multivariate Cox regression analysis was used to examine the association between
      clinical and laboratory parameters and survival. RESULTS: A total of 48 patients
      were identified. Median OS was 6.2 months [95% confidence interval (CI): 3.9
      7.6]. In multivariate analysis, age < 65 years, baseline total lymphocyte count
      (TLC) < 1500/ul and presence of peritoneal metastases were associated with
      shorter OS. Most adverse events were grade 1-2 and included: anemia (52.3%),
      leukocytopenia (40.9%), neutropenia (59.1%), nausea (25.0%), vomiting (31.8%),
      diarrhea (31.8%), anorexia (29.5%) and fatigue (43.2%). Febrile neutropenia
      occurred in three patients (6.8%). Nine patients (20.5%) experienced a toxicity
      grade 3-4 of any kind. CONCLUSIONS: This retrospective analysis confirms clinical
      effectiveness and manageable toxicity of second-line irinotecan in an unselected
      cohort of advanced GEA patients. Age < 65 years, baseline TLC < 1500/ul and
      presence of peritoneal metastases were independent prognostic factors associated
      with shorter OS.

PMID- 28491143
TI  - Probiotic engineering: towards development of robust probiotic strains with
      enhanced functional properties and for targeted control of enteric pathogens.
AB  - There is a growing concern about the increase in human morbidity and mortality
      caused by foodborne pathogens. Antibiotics were and still are used as the first
      line of defense against these pathogens, but an increase in the development of
      bacterial antibiotic resistance has led to a need for alternative effective
      interventions. Probiotics are used as dietary supplements to promote gut health
      and for prevention or alleviation of enteric infections. They are currently used
      as generics, thus making them non-specific for different pathogens. A good
      understanding of the infection cycle of the foodborne pathogens as well as the
      virulence factors involved in causing an infection can offer an alternative
      treatment with specificity. This specificity is attained through the
      bioengineering of probiotics, a process by which the specific gene of a pathogen
      is incorporated into the probiotic. Such a process will subsequently result in
      the inhibition of the pathogen and hence its infection. Recombinant probiotics
      offer an alternative novel therapeutic approach in the treatment of foodborne
      infections. This review article focuses on various strategies of bioengineered
      probiotics, their successes, failures and potential future prospects for their
      applications.

PMID- 28491145
TI  - Combination of metformin and curcumin targets breast cancer in mice by
      angiogenesis inhibition, immune system modulation and induction of p53
      independent apoptosis.
AB  - BACKGROUND: The effects of metformin (MET) and curcumin (CUR) single treatments
      have been tested against breast cancer; however, their combination has not been
      explored. Here, we evaluated the antitumor activity of MET and CUR combination
      against breast cancer in mice. MATERIALS AND METHODS: The antiproliferative
      activity of single and combined treatments against breast cancer cell lines was
      determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was
      examined in EMT6/P cells. In vivo studies were carried out by inoculating BALB/c
      mice with EMT6/P cells and examining tumor growth and apoptosis induction in
      tumor sections. Furthermore, serum levels of different cytokines and
      transaminases and creatinine were measured to detect the immune response and
      toxicity, respectively. RESULTS: The combination treatment exhibited the highest
      effects against tumor proliferation and growth. It significantly reduced VEGF
      expression, induced Trp53 independent apoptosis, triggered Th2 immune response
      and showed no toxicity. CONCLUSION: The combination can be a potential
      therapeutic option to treat breast cancer. However, further testing is needed to
      measure the exact serum levels of MET and CUR and to further explain the obtained
      results.

PMID- 28491146
TI  - PARP inhibitors in ovarian cancer: evidence, experience and clinical potential.
AB  - Inhibitors of poly(ADP-ribose) polymerase (PARP) are considered one of the most
      active and exciting new therapies for the treatment of ovarian cancer. The
      anticancer activity of PARP inhibitors is based on the DNA repair vulnerability
      of many ovarian cancer cells, and multiple mechanisms of action of PARP
      inhibitors have been identified. As single agents, PARP inhibitors have
      demonstrated their greatest activity in ovarian cancer cells that harbor
      mutations in BRCA genes. Additionally, recent phase III studies have shown that
      single-agent PARP inhibitor activity extends beyond BRCA-related cancers and can
      benefit patients with ovarian cancers that do not have known BRCA mutations,
      especially when clinical characteristics such as platinum sensitivity and high
      grade serous histology are present. PARP inhibitors have also been combined with
      chemotherapy, however, overlapping myelosuppression observed with PARP inhibitor
      and chemotherapy combinations has hampered development of these combinations.
      Contrariwise, PARP inhibitor and biologic agent combinations, specifically
      antiangiogenic agents, appear well tolerated and show promising activity in both
      BRCA mutated (BRCAm) and BRCA wild-type (BRCAwt) cancers. Currently, multiple
      clinical trials are underway examining the antitumor activity of PARP inhibitor
      combination therapy.

PMID- 28491147
TI  - A clinical guide to the management of genitourinary symptoms in breast cancer
      survivors on endocrine therapy.
AB  - There is increasing attention and concern about managing the adverse effects of
      adjuvant endocrine therapy for women with early breast cancer as the side effects
      of therapy influence compliance and can impair quality of life (QoL). Most side
      effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are
      directly related to estrogen deprivation, and the symptoms are similar to those
      experienced during natural menopause but appear to be more severe than that seen
      in the general population. Prolonged estrogen deprivation may lead to atrophy of
      the vulva, vagina, lower urinary tract and supporting pelvic structures,
      resulting in a range of genitourinary symptoms that can in turn lead to pain,
      discomfort, impairment of sexual function and negatively impact on multiple
      domains of QoL. The genitourinary side effects may be prevented, reduced and
      managed in most cases but this requires early recognition and appropriate
      treatment. We provide an overview of practical clinical approaches to
      understanding the pathophysiology and the management of genitourinary symptoms in
      postmenopausal women receiving adjuvant endocrine therapy for breast cancer.

PMID- 28491148
TI  - Moving beyond vascular endothelial growth factor-targeted therapy in renal cell
      cancer: latest evidence and therapeutic implications.
AB  - Renal cell cancer (RCC) continues to be among the most lethal malignancies in the
      USA. Introduction of anti-vascular epidermal growth factor receptor tyrosine
      kinase inhibitors over a decade ago resulted in improvement in disease outcomes,
      but further development of new therapies largely stagnated for many years. More
      recently, a better understanding of disease biology and treatment-resistance
      patterns has led to a second renaissance in drug development, with the anti
      programmed cell death protein 1 immune checkpoint inhibitor, nivolumab, paving
      the way for additional therapies entering clinical trial testing in the treatment
      of RCC.

PMID- 28491150
TI  - Dynamic silencing of somatic L1 retrotransposon insertions reflects the
      developmental and cellular contexts of their genomic integration.
AB  - BACKGROUND: The ongoing mobilization of mammalian transposable elements (TEs)
      contributes to natural genetic variation. To survey the epigenetic control and
      expression of reporter genes inserted by L1 retrotransposition in diverse
      cellular and genomic contexts, we engineered highly sensitive, real-time L1
      retrotransposon reporter constructs. RESULTS: Here we describe different patterns
      of expression and epigenetic controls of newly inserted sequences retrotransposed
      by L1 in various somatic cells and tissues including cultured human cancer cells,
      mouse embryonic stem cells, and tissues of pseudofounder transgenic mice and
      their progeny. In cancer cell lines, the newly inserted sequences typically
      underwent rapid transcriptional gene silencing, but they lacked cytosine
      methylation even after many cell divisions. L1 reporter expression was reversible
      and oscillated frequently. Silenced or variegated reporter expression was
      strongly and uniformly reactivated by treatment with inhibitors of histone
      deacetylation, revealing the mechanism for their silencing. By contrast, de novo
      integrants retrotransposed by L1 in pluripotent mouse embryonic stem (ES) cells
      underwent rapid silencing by dense cytosine methylation. Similarly, de novo
      cytosine methylation also was identified at new integrants when studied in
      several distinct somatic tissues of adult founder mice. Pre-existing L1 elements
      in cultured human cancer cells were stably silenced by dense cytosine
      methylation, whereas their transcription modestly increased when cytosine
      methylation was experimentally reduced in cells lacking DNA methyltransferases
      DNMT1 and DNMT3b. As a control, reporter genes mobilized by piggyBac (PB), a DNA
      transposon, revealed relatively stable and robust expression without apparent
      silencing in both cultured cancer cells and ES cells. CONCLUSIONS: We hypothesize
      that the de novo methylation marks at newly inserted sequences retrotransposed by
      L1 in early pre-implantation development are maintained or re-established in
      adult somatic tissues. By contrast, histone deacetylation reversibly silences L1
      reporter insertions that had mobilized at later timepoints in somatic development
      and differentiation, e.g., in cancer cell lines. We conclude that the cellular
      contexts of L1 retrotransposition can determine expression or silencing of newly
      integrated sequences. We propose a model whereby reporter expression from somatic
      TE insertions reflects the timing, molecular mechanism, epigenetic controls and
      the genomic, cellular and developmental contexts of their integration.

PMID- 28491152
TI  - Temporal profile of PM10 and associated health effects in one of the most
      polluted cities of the world (Ahvaz, Iran) between 2009 and 2014.
AB  - Ahvaz, Iran ranks as the most polluted city of the world in terms of PM10
      concentrations that lead to deleterious effects on its inhabitants. This study
      examines diurnal, weekly, monthly and annual fluctuations of PM10 between 2009
      and 2014 in Ahvaz. Health effects of PM10 levels are also assessed using the
      World Health Organization AirQ software. Over the study period, the mean PM10
      level in Ahvaz was 249.5 ug m-3, with maximum and minimum values in July (420.5
      ug m-3) and January (154.6 ug m-3), respectively. The cumulative diurnal PM10
      profile exhibits a dominant peak between 08:00-11:00 (local time) with the lowest
      levels in the afternoon hours. While weekend PM10 levels are not significantly
      reduced as compared to weekdays, an anthropogenic signature is instead observed
      diurnally on weekdays, which exhibit higher PM10 levels between 07:00-17:00 by an
      average amount of 14.2 ug m-3 as compared to weekend days. PM10 has shown a
      steady mean-annual decline between 2009 (315.2 ug m-3) and 2014 (143.5 ug m-3).
      The AirQ model predicts that mortality was a health outcome for a total of 3777
      individuals between 2009 and 2014 (i.e., 630 per year). The results of this study
      motivate more aggressive strategies in Ahvaz and similarly polluted desert cities
      to reduce the health effects of the enormous ambient aerosol concentrations.

PMID- 28491153
TI  - Estrogen receptor-positive primary squamous cell carcinoma of the breast.
AB  - Pure primary squamous cell carcinoma of the breast (SCCB) represents around 0.1%
      of breast carcinomas. Diagnosis requires independence from adjacent skin without
      metastatic disease. SCCB is often large at presentation with nonspecific
      mammographic and ultrasound findings. It is typically hormone receptor negative
      and aggressive. Mastectomy and adjuvant chemotherapy is the most common
      treatment, although treatment guidelines are not well established. We present a
      case of pure primary SCCB detected by high risk screening mammogram and treated
      with breast conserving surgery, chemotherapy, and radiation. We discuss clinical,
      radiologic, and pathologic findings.

PMID- 28491151
TI  - Methylation of DIRAS1 promotes colorectal cancer progression and may serve as a
      marker for poor prognosis.
AB  - BACKGROUND: DIRAS1 is a new member of the Ras gene family. It was described as a
      potential tumor suppressor in human glioblastomas and esophageal cancer. The role
      of DIRAS1 in colorectal cancer remains unclear. METHODS: To explore the
      epigenetic changes and function of DIRAS1 in human colorectal cancer, we studied
      ten colorectal cancer cell lines and 146 primary colorectal cancer samples and 50
      matched adjacent samples using semi-quantitative reverse transcription PCR,
      immunohistochemistry, methylation-specific PCR and bisulfite sequencing, western
      blot, flow cytometry, and transwell assays. RESULTS: DIRAS1 expression was found
      in DKO and HCT116 cells, while reduced expression was detected in LoVo, SW48,
      LS180, and SW620 cells, and there was no expression detected in DLD1, HT29, RKO,
      and SW480 cells. Complete methylation was found in the promoter region of DLD1,
      HT29, RKO, and SW480 cells. Partial methylation was detected in LoVo, LS180,
      SW48, and SW620 cells, and unmethylation was found in DKO and HCT116 cells. These
      results indicate that promoter region methylation correlated with loss of/reduced
      expression of DIRAS1. Re-expression of DIRAS1 was induced by 5-aza-2'
      deoxycytidine, suggesting that the expression of DIRAS1 is regulated by promoter
      region methylation. DIRAS1 was methylated in 47.3% (69/146) of primary colorectal
      cancer samples, no methylation was found in non-cancerous colonic tissue samples.
      Methylation of DIRAS1 was significantly associated with TNM stage (P < 0.05) and
      short survival time (P = 0.0121). DIRAS1 induced apoptosis and inhibited cell
      proliferation, migration, and invasion in colorectal cancer. Finally, DIRAS1
      suppressed colorectal cancer cell xenograft growth in nude mice. CONCLUSIONS:
      DIRAS1 is frequently methylated in human colorectal cancer and the expression of
      DIRAS1 is regulated by promoter region methylation. Methylation of DIRAS1 is a
      marker of poor prognosis in human colorectal cancer.

PMID- 28491154
TI  - Spuriously aggressive features of a lactating adenoma prompting repeated
      biopsies.
AB  - We present an atypical presentation of a common pregnancy-related breast mass, a
      lactating adenoma with imaging and pathologic correlation. The patient presented
      with a rapidly enlarging left breast mass associated with skin changes and severe
      pain in the perinatal period. Core biopsies were considered discordant, and the
      patient went on to surgical excision for the definitive diagnosis of an infarcted
      lactating adenoma. The symptoms of infarction may obscure the diagnosis of common
      entities and result in additional evaluation.

PMID- 28491155
TI  - Focal angiomatosis of the breast with MRI and histologic features.
AB  - Angiomatosis of the breast is an extremely rare, benign vascular lesion. This is
      a diagnostic challenge, given the limited number of cases reported in the
      literature. Additionally, due to similar features of the more common malignant
      vascular tumor, angiosarcoma familiarity with angiomatosis in the differential
      diagnosis is important. We present a case of angiomatosis of the breast in a 28
      year-old female. The lesion presented as an incidental enhancing mass on computed
      tomography scan initially and subsequent mammogram and ultrasound studies did not
      show a correlate. Next, magnetic resonance imaging demonstrated an enhancing
      correlate for which magnetic resonance imaging biopsy and subsequent excisional
      biopsy demonstrated angiomatosis of the breast.

PMID- 28491157
TI  - Infracardiac type total anomalous pulmonary venous return with obstruction and
      dilatation of portal vein.
AB  - Total anomalous pulmonary venous return (TAPVR), also known as total anomalous
      pulmonary venous connection, is a congenital cardiovascular malformation that
      presents itself in the neonatal period, with cyanosis and tachypnea. There are 4
      types of TAPVR with the mixed type being the least common. Any type of TAPVR may
      be associated with obstruction as result of flow redirection through the liver
      parenchyma before it may return to the heart, but infracardiac is the most common
      one. We report a case of a 10-hour-old female, with a mixed (cardiac and
      infracardiac) TAVPR with obstruction, that showed drainage to the coronary sinus
      and the portal vein, as the other classic findings in TAVPR, made with computed
      tomography angiography and echocardiogram. The patient was taken to surgical
      repair, but unfortunately died during the procedure because of multiple
      complications.

PMID- 28491156
TI  - Primary lung carcinoid metastatic to the breast.
AB  - Lung carcinoid tumors account for approximately 2% of lung cancers, with 10% of
      the tumors represented by the atypical type. While atypical carcinoids are
      metastatic to intrathoracic lymph nodes in approximately half of the cases on the
      initial presentation, distant metastases are seen in only 20% of the patients and
      are found most frequently in bones, liver, adrenal glands, and brain. We present
      a case of an unusual metastatic disease to the breast in 51-year-old female who
      developed a new breast mass 2 years after left lower lobectomy due to atypical
      carcinoid tumor. Atypical pulmonary carcinoid metastases to the breast are
      exceptionally uncommon, yet they are important considerations for appropriate
      management, especially with an anamnesis of this neoplasm.

PMID- 28491158
TI  - An unusual cause of atrial fibrillation in a young active duty soldier.
AB  - Coronary artery fistula (CAF) is an abnormality in which the coronary artery has
      an anomalous connection with a venous structure such as the coronary sinus or
      atrium. CAF is usually congenital, but may be acquired. The prevalence in the
      general population is low with many asymptomatic and discovered incidentally.
      When symptomatic, CAF may present with dyspnea, decreasing functional capacity,
      and/or arrhythmia. We report a case of a young otherwise healthy active duty male
      with progressive symptoms of dizziness and exertional fatigue with paroxysmal
      atrial fibrillation. An electrically negative, but symptomatically positive
      stress test led to further workup with coronary computed tomography angiogram,
      which unexpectedly revealed large coronary fistulas between the aneurysmal right
      coronary artery and coronary sinus and the dilated left circumflex artery with
      probable collateralization to the coronary sinus. Cardiac magnetic resonance
      imaging and cardiac catheterization supported these findings and demonstrated no
      evidence of significant shunting.

PMID- 28491159
TI  - Huge idiopathic pulmonary artery aneurysm.
AB  - A pulmonary artery aneurysm is an uncommon anomaly. The clinical manifestations
      are mostly nonspecific, and management is controversial. We report a case of a 67
      year-old woman with a main pulmonary artery aneurysm who did not take surgical
      intervention. Subsequently, there was no increase in size for 3 years.

PMID- 28491160
TI  - Asymptomatic left ventricular hemangioma.
AB  - Cardiac hemangiomas are very rare benign neoplasms that are usually asymptomatic.
      Although there are often found incidentally during echocardiography, other
      imaging modalities such as computed tomography, magnetic resonance imaging, and
      coronary angiography are needed to establish a diagnosis. Surgical excision is
      therefore recommended to confirm the diagnosis and avoid potential complications.
      We report a case of asymptomatic cardiac hemangioma that was discovered
      incidentally during echocardiography.

PMID- 28491161
TI  - Ruptured superficial femoral artery aneurysm: a case report.
AB  - A 96-year-old male presented with left lower extremity pain, swelling, and
      vascular compromise. Computed tomographic angiography revealed an actively
      rupturing distal superficial femoral artery aneurysm. The patient underwent
      prompt aneurysm excision with graft interposition and had a successful
      postoperative outcome. Our case illustrates the critical role of imaging in
      establishing a definitive diagnosis and preventing mortality.

PMID- 28491162
TI  - Ectopic mediastinal parathyroid adenoma localized with four-dimensional CT: a
      case report.
AB  - We present a case of an ectopic mediastinal parathyroid adenoma in a 58-year-old
      male patient. We show how different imaging modalities were successfully used to
      reach a diagnosis. We particularly focus on the role of four-dimensional CT scan
      in preoperative localization of ectopic adenomas and discuss how diverse imaging
      modalities can be integrated in the workup of ectopic parathyroid adenomas.

PMID- 28491163
TI  - Pulmonary inflammatory myofibroblastic tumor: report of 2 cases with radiologic
      pathologic correlation.
AB  - Inflammatory myofibroblastic tumor is a rare benign tumor that affects most
      commonly children and young adults. In the lung, it comprises less than 1% of all
      neoplasms. The authors describe the clinical, radiological, and pathologic
      features of 2 cases of incidentally discovered pulmonary inflammatory
      myofibroblastic tumors.

PMID- 28491164
TI  - Spinal subarachnoid and subdural hematoma presenting as a Brown-Sequard-like
      myelopathy following minor trauma in a patient on dabigatran etexilate.
AB  - Dabigatran etexilate is a relatively new anticoagulant from the class of direct
      thrombin inhibitors which is administered orally and does not require routine
      blood work monitoring. Dabigatran may be attractive to both clinicians and
      patients because of both its convenience and efficacy; however, clinical
      complications are still being elucidated. Here, we present a previously
      unreported case of spinal subarachnoid and subdural hematoma presenting as a
      Brown-Sequard-like myelopathy in a patient after minor trauma in the setting of
      Dabigatran anticoagulation.

PMID- 28491165
TI  - Carbon dioxide angiography and arterial embolization could successfully control
      postpartum uterine hemorrhage for the patient with hypersensitivity to iodine
      compound.
AB  - Transcatheter arterial embolization has become a common management option for
      intractable postpartum uterine hemorrhage. Iodinated contrast agents are commonly
      used for embolotherapy but cannot be used in patients with renal dysfunction or
      iodine allergy. A 37-year-old woman spontaneously delivered a healthy girl but
      developed severe postpartum uterine hemorrhage, probably due to placenta accrete.
      Contrast-enhanced computed tomography revealed extravasation of the iodinated
      contrast agent into the uterine cavity. The patient subsequently developed
      allergic reaction to this agent. After recovery from the allergic reaction with
      appropriate treatment, we performed carbon dioxide angiography and found that the
      extravasation originated from the right uterine artery. Embolization of the right
      internal iliac artery was performed, and hemostasis was verified. Based on this
      experience, we suggest carbon dioxide angiography and arterial embolization can
      be used for treating intractable postpartum hemorrhage in patients with iodinated
      contrast media allergy or renal dysfunction.

PMID- 28491166
TI  - Toothpick meningitis.
AB  - A 66-year-old male with a history of hypertension, back pain, diverticulosis and
      anal fistula presents with acute onset syncopal episodes, worsening back pain,
      and altered mental status. The patient exhibited considerable leukocytosis but
      was hemodynamically stable. CT imaging of the head revealed a gas pattern in the
      posterior fossa and velum interpositum. CT imaging of the abdomen and pelvis
      revealed a needle-like foreign body traversing the left sacrum to the sigmoid
      colon. A lumbar puncture revealed meningitis. Flexible sigmoidoscopies were
      performed without successful visualization of the foreign body. An explorative
      laparoscopy was successfully performed, enabling retrieval of what was determined
      to be a wooden toothpick. The patient remained hemodynamically stable with
      persistent altered mental status and was eventually discharged after completion
      of antibiotics on day 47 of hospitalization. This case illustrates a rare
      complication of ingesting a sharp foreign body that was identified by CT of the
      brain and abdomen/pelvis with successful surgical repair.

PMID- 28491167
TI  - Disappearing portal venous gas in acute pancreatitis and small bowel ischemia.
AB  - We report an usual case of hepatic portal venous gas (HPVG) in the setting of
      acute pancreatitis and small bowel ischemia. Interestingly, the HPVG disappeared
      within 2 hours of the original computed tomography scan, despite the patient
      having small bowel ischemia. The patient had a complicated clinical course, dying
      62 days postadmission. This case highlights that HPVG in setting of acute
      pancreatitis and small bowel ischemia has a very high morbidity and mortality,
      requiring early detection and aggressive surgical management.

PMID- 28491169
TI  - Submucosal esophageal hematoma precipitated by chronic idiopathic
      thrombocytopenic purpura.
AB  - Submucosal esophageal hematoma is an uncommon clinical entity. It can occur
      spontaneously or secondary to trauma, toxins, medical intervention, and in this
      case, coagulopathy. Management of SEH is supportive and aimed at its underlying
      cause. This article reports an 81-year-old male patient with chronic idiopathic
      thrombocytopenic purpura and hypertension that develops a submucosal esophageal
      hematoma.

PMID- 28491168
TI  - Serous cystadenocarcinoma of the spleen.
AB  - The commonly seen primary malignant neoplasms of the spleen are angiosarcoma and
      lymphoma. We present a case of serous cystadenocarcinoma of the spleen. It was
      presumed to be originated from dropped nonmalignant ovarian tissue, which was
      accidentally implanted to the splenic surface during hysterectomy and bilateral
      salpingooophorectomies for torsion of right fallopian tube 9 and half years ago
      and transformed into serous cystadenocarcinoma later. Computed tomography
      demonstrated a multilocular predominantly cystic tumor with internal soft tissue
      components in the spleen.

PMID- 28491170
TI  - High-grade transitional cell carcinoma masquerading as a xanthogranulomatous
      pyelonephritis and perinephric abscess.
AB  - Xanthogranulomatous pyelonephritis (XGPN) is an atypical long-term pyelonephritis
      with destruction of renal parenchyma and a long-term inflammatory infiltrate of
      macrophages. Reported presentations of transitional cell carcinoma (TCC) are
      different. A 73-year-old woman presented with loin pain, prostration, and fever.
      Computed tomography scan revealed poor cortical enhancement of the kidney, but
      some of the images bore resemblance to the characteristic "bear's paw" sign,
      consistent with XGPN with a 7-cm perinephric collection. She was provisionally
      diagnosed as severe acute pyelonephritis, possibly XGPN, with abscess. In view of
      the poor clinical condition, decision was made to perform nephrectomy. Histology
      revealed a G3pT4 high grade TCC with perineural and vascular invasion and
      reactive xanthogranulomatous inflammatory response. There are few reports of
      concomitant XGPN and TCC affecting the kidney. However, there has not been any
      mention of XGPN and TCC presenting as acute pyelonephritis and perinephric
      abscess so far.

PMID- 28491171
TI  - Transverse mobility of pelvic kidney causing left lower extremity deep venous
      thrombosis.
AB  - A case of May-Thurner-like syndrome was found to be a result of a pelvic kidney
      compressing the left common iliac vein. Cross-sectional imaging demonstrated
      transverse mobility of the pelvic kidney which has not been described previously.
      The ectopic kidney's mobility resulted in intermittent venous compression. In a
      patient with recurrent lower extremity deep venous thrombosis and a pelvic
      kidney, the possibility of movement of the kidney resulting in venous compression
      needs to be considered.

PMID- 28491172
TI  - Acquired uterine arteriovenous fistula following dilatation and curettage: an
      uncommon cause of vaginal bleeding.
AB  - Dysfunctional uterine bleeding is a common presentation of women in the emergency
      department. We describe the case of a 33-year-old female who presented with
      intermittent spotting due to an acquired uterine AVF. The patient underwent a
      transvaginal pelvic ultrasound as well as a CT angiogram. The patient was treated
      conservatively and elected to undergo uterine artery embolization in an effort to
      preserve fertility. She successfully delivered a healthy baby boy at 39-week
      gestation via an emergent caesarian section due to a prolapsed umbilical cord 17
      months after undergoing the uterine artery embolization.

PMID- 28491173
TI  - Radiographically occult pulmonary metastases from gestational trophoblastic
      neoplasia.
AB  - Gestational trophoblastic neoplasia (GTN) is a spectrum of diseases including
      partial and complete hydatidiform moles, placental site trophoblastic tumor, and
      choriocarcinoma. One of the most important considerations is recognition of the
      possibility of GTN after molar pregnancy or even normal pregnancy. It is common
      practice to use chest x-ray for the detection of pulmonary metastasis. Computed
      tomography imaging of the lungs is ordered if lung lesions are noted on chest x
      rays. However, understanding the limitations of chest x-rays is important for
      detecting smaller pulmonary lesions. We present a patient with GTN and pulmonary
      metastasis after having received 2 negative chest x-rays.

PMID- 28491174
TI  - Diagnosis of abnormally invasive posterior placentation: the role of MR imaging.
AB  - Abnormally invasive placentation is becoming more common with a recent increase
      in cesarean sections and maternal age, among other risk factors. Ultrasonography
      is the first line-imaging, but it can be difficult to diagnose when limiting
      factors are present. Failure to recognize this serious placental abnormality
      precludes us from making the appropriate plan for the delivery and consequently
      can lead to fatal results. In this report, we present a case in which magnetic
      resonance imaging was used to diagnose posterior placenta increta missed by
      multiple sonographic examinations in a patient with previous myomectomies, and we
      also include a review of the literature on this topic. It is our conclusion that
      magnetic resonance imaging is superior to sonography to diagnose abnormally
      invasive placentation in cases of posterior placenta previa and high pretesting
      probability.

PMID- 28491175
TI  - MRI characteristics of primary fallopian tube choriocarcinoma: a case report.
AB  - Tubal choriocarcinoma is uncommon, and its magnetic resonance imaging
      characteristics have not yet been reported. In this report, a 39-year-old woman
      presented with irregular painless vaginal bleeding and a palpable left lower
      abdominal lump for 2 months following 6 weeks' amenorrhea and positive urine
      pregnancy test. Her serum beta-human chorionic gonadotropin value was
      significantly increased. Ultrasound revealed a left adnexal mass, which showed no
      blood flow signal on Color doppler flow imaging. A further MR examination showed
      a well-defined cystic-solid mass with cystic component accounting for a large
      proportion in the left lower abdomen. The solid part with mixed signals resembled
      a honeycomb. Finally, the left tubal choriocarcinoma was confirmed by pathology.
      When the solid parts of cystic-solid mass appeared as "honeycomb appearance" and
      the ovaries were normal by magnetic resonance imaging, together with typical
      symptoms and significantly elevated beta-human chorionic gonadotropin values,
      radiologists should feel more confident in suspecting tubal choriocarcinoma and
      reporting it on their differential.

PMID- 28491176
TI  - Nontraumatic urinary bladder rupture presenting as renal pseudo-failure and
      ascites.
AB  - A 24-year-old man, with past medical history significant only for nocturnal
      enuresis until the age of 12 years, presented to the emergency department with
      acute abdominal pain after an episode of difficulty with micturition in the
      middle of the night. On presentation, physical examination was suggestive of
      ascites and laboratories revealed an elevated serum creatinine of 1.88 mg/dL. He
      was subsequently found to have a ruptured bladder, without any inciting trauma,
      which required surgical repair. His only surgical history is an unknown,
      apparently urologic, surgery when he was 11-12 years old. The patient's unique
      presentation prompts discussion of bladder rupture and its manifestations, the
      role of clinical information in informing imaging protocol, and the importance of
      sagittal images in identifying pathology.

PMID- 28491177
TI  - Incidentally discovered well-differentiated retroperitoneal liposarcoma with
      inguinal canal herniation: report of 2 cases.
AB  - Well-differentiated retroperitoneal liposarcomas are slow growing and low-grade
      tumors, reaching usually huge size before being symptomatic and so diagnosed,
      therefore with increase of the surgical risk and of the probability of
      dedifferentiation. Inguinal location of these tumors is unusual and rarely
      diagnosed.

PMID- 28491178
TI  - Ossifying fibroma: an uncommon differential diagnosis for T2-hypointense
      sinonasal masses.
AB  - Ossifying fibroma is a benign fibro-osseous lesion that occurs most commonly in
      the mandible of female patients. In rare cases, it affects the nasal cavity. The
      magnetic resonance imaging features may vary depending on the amount of fibrous
      and bony tissue in its composition. In these tumors, T2-hypointensity is a
      feature described in the peripheral ossified areas of the lesion, but it may
      present diffusely, especially when the degree of ossification is extensive. In
      this scenario, this particular characteristic on T2-weighted imaging is
      superimposable to the commonly described appearance of other lesions, such as non
      Hodgkin's lymphoma, melanoma, and other sinonasal neoplasms with high cellularity
      and high nucleocytoplasmic ratio. In the present study, we report a case of
      ossifying fibroma of the nasal cavity that presented as a diffusely and
      homogeneously T2-hypointense mass, a finding that may cause difficulty in the
      differential diagnosis with other expansive sinonasal lesions.

PMID- 28491179
TI  - Transhepatic embolization of a congenital intrahepatic portosystemic shunt for
      the treatment of hepatic encephalopathy in a noncirrhotic patient using Amplatzer
      vascular plug device.
AB  - A 73-year-old male with no history of liver disease was hospitalized for
      weakness, confusion, ataxia, and new onset hepatic encephalopathy with
      hyperammonemia. After management with lactulose and rifaximin, his symptoms
      persisted, and he underwent transjugular liver biopsy. Biopsy showed normal
      liver, but a portosystemic shunt was incidentally identified on postbiopsy
      venogram. The patient underwent occlusion of the shunt with two Amplatzer
      vascular plugs and four Nester coils. Following embolization, the patient's
      symptoms resolved completely. Our case reports one of the oldest adults to
      present with symptoms from a congenital portosystemic shunt. Congenital
      portosystemic shunts can be considered in patients with new onset hepatic
      encephalopathy in the absence of underlying liver disease. Prognosis after
      embolization of congenital portosystemic shunt is great, and embolization may
      result in full reversal of symptoms.

PMID- 28491180
TI  - Transbiliary intravascular ultrasound-guided diagnostic biopsy of an inaccessible
      pancreatic head mass.
AB  - Percutaneous image-guided biopsies of pancreatic malignancies may prove
      challenging and nondiagnostic due to a variety of anatomic considerations. For
      patients with complex post-surgical anatomy, such as a Roux-en-Y gastric bypass,
      diagnosis via endoscopic ultrasound with fine-needle aspiration may not be
      possible because of an inability to reach the proximal duodenum. This report
      describes the first diagnostic case of transbiliary intravascular ultrasound
      guided biopsy of a pancreatic head mass in a patient with prior Roux-en-Y gastric
      bypass for which a diagnosis could not be achieved via percutaneous and
      endoscopic approaches. Transbiliary intravascular ultrasound-guided biopsy
      resulted in a diagnosis of pancreatic adenocarcinoma, allowing the initiation of
      chemotherapy.

PMID- 28491181
TI  - TIPS performed in a patient with complete portal vein thrombosis.
AB  - Portal vein thrombosis is common in cirrhotic patients and results in increased
      morbidity and mortality. Transjugular intrahepatic portosystemic shunt (TIPS)
      creation is a well-established therapy for refractory variceal bleeding and
      refractory ascites in patients who do not tolerate repeated large volume
      paracentesis. Experience and technical improvements have led to improved TIPS
      outcomes that have encouraged an expanded application. Complete portal vein
      thrombosis has come a long way from being a contraindication to an indication for
      TIPS procedure. As experience and technology have evolved, the ultrasound
      guidance transvenous access of portal vein from the hepatic vein help in overall
      higher success rate of performing the TIPS procedure and reducing the procedure
      related complications.

PMID- 28491182
TI  - Aortoenteric fistulae temporization and treatment: lessons learned from a
      multidisciplinary approach to 3 patients.
AB  - Aortoenteric fistulae are life-threatening conditions characterized by abnormal
      communications between the aorta and gastrointestinal tract. Aortoenteric
      fistulae may be characterized by the triad of bleeding, abdominal pain, or a
      pulsatile abdominal mass. Although hemorrhage is the most common presentation, it
      does not always occur; thus, patients may present with nonspecific symptoms.
      Computed tomography angiography findings suggestive of aortoenteric fistulae
      include ectopic gas within or adjacent to the aorta, discontinuity of the aortic
      wall, bowel wall thickening, and extravasation of contrast into the bowel.
      Endovascular treatments include retrograde balloon occlusion of the aorta and
      stent-graft deployment as well as coil, fibrin, and glue embolization of the
      fistulous tract. This report describes 3 cases of aortoenteric fistulae
      temporized and treated by interventional radiology and vascular and cardiac
      surgery at a single institution in an effort to increase awareness of this
      important clinical condition.

PMID- 28491183
TI  - Tine after tine: a varied approach to the removal of a long-standing IVC filter.
AB  - Inferior vena cava filters are important tools used to help prevent life
      threatening pulmonary embolisms in hospitalized patients with contraindications
      to pharmacological prophylactic anticoagulation. This is a case report of a
      patient who had an inferior vena cava filter placed after a traumatic subdural
      hematoma. He made a complete recovery but was lost to follow-up until he
      presented 1825 days after filter deployment with abdominal pain discovered to be
      from penetration of the filter tines outside the lumen and into adjacent
      structures. We describe a case complicated by fibrotic tine entrapment with
      penetration to surrounding structures and discuss the technical approach used to
      free and eventually remove the long-standing filter.

PMID- 28491184
TI  - Feasibility of transfemoral hepatic vein/wedged portal venous pressure
      measurement in total artificial heart.
AB  - The development of technology and limitation of numerous ventricular assist
      devices has increased usage of the total artificial heart (TAH) for mechanical
      circulatory support. A primary important feature of TAH is that it is one of the
      few mechanical circulatory support devices that provides biventricular support.
      As the number of patients with TAH rises, spreading awareness about the device in
      the interventional radiology community is important.

PMID- 28491185
TI  - Extra-adrenal pheochromocytoma at the organ of Zuckerkandl: a case report and
      literature review.
AB  - Pheochromocytomas and paragangliomas are tumors that occur in characteristic
      locations and are commonly detected on imaging studies. A correct diagnosis is
      important because of differences in associated neoplasms, risk for malignancy,
      and need for genetic testing. In addition, associated complications, including
      death, can be avoided if appropriately recognized and treated. Here, we report a
      rare case of an extra-adrenal paraganglioma of the organ of Zuckerkandl.

PMID- 28491186
TI  - Quantifying spasticity in individual muscles using shear wave elastography.
AB  - Spasticity is common following stroke; however, high subject variability and
      unreliable measurement techniques limit research and treatment advances. Our
      objective was to investigate the use of shear wave elastography (SWE) to
      characterize the spastic reflex in the biceps brachii during passive elbow
      extension in an individual with spasticity. The patient was a 42-year-old right
      hand-dominant male with history of right middle cerebral artery-distribution
      ischemic infarction causing spastic left hemiparesis. We compared Fugl-Meyer
      scores (numerical evaluation of motor function, sensation, motion, and pain),
      Modified Ashworth scores (most commonly used clinical assessment of spasticity),
      and SWE measures of bilateral biceps brachii during passive elbow extension. We
      detected a catch that featured markedly increased stiffness of the brachialis
      muscle during several trials of the contralateral limb, especially at higher
      extension velocities. SWE was able to detect velocity-related increases in
      stiffness with extension of the contralateral limb, likely indicative of the
      spastic reflex. This study offers optimism that SWE can provide a rapid, real
      time, quantitative technique that is readily accessible to clinicians for
      evaluating spasticity.

PMID- 28491187
TI  - Giant cell tumor of the tendon seath of the tendinous insertion in pes anserinus.
AB  - A 56-year-old woman with a palpable lump in the medial surface of her left knee
      was referred for diagnostic workup with magnetic resonance imaging. The lesion
      was pathogically confirmed to be a giant cell tumor of the tendon seath. The MR
      features of the lesion are presented.

PMID- 28491188
TI  - Brace yourself: an unusual case of knee pain, an extradigital glomangioma of the
      knee.
AB  - The differential diagnosis for knee pain is extensive. Glomus tumors comprise
      approximately 1.6% of soft-tissue tumors in the extremities. Classic subungual
      tumors occur more frequently in women, whereas ectopic locations are more common
      in men. Unusual locations include the stomach; lungs; trachea; bones; intestines;
      fallopian tubes; and intraneural, neuromal, and intravenous locations. We present
      the case of a 50-year-old man with a 12-year history of enlarging right knee mass
      found to be a glomangioma. This case report discusses the incidence,
      presentation, imaging characteristics, histology, and management of glomus tumors
      of the knee.

PMID- 28491189
TI  - Asymmetric bone mineral density in the bilateral femoral necks due to gluteal
      implants: a case report.
AB  - Interpreting asymmetric bone mineral density in the bilateral hips on dual energy
      x-ray absorptiometry requires investigation into the potential causes, both real
      and artifactual. Silicone gluteal implants have been reported to cause abnormally
      elevated bone mineral density. We report a case of abnormally low bone mineral
      density in a patient with bilateral gluteal implants. This is likely due to
      patient positioning and inability of the computer to identify the superior margin
      of the proximal femur and the femoral neck.

PMID- 28491190
TI  - Pyogenic brain abscess with atypical features resembling glioblastoma in advanced
      MRI imaging.
AB  - Differentiation between infectious and neoplastic brain processes is crucial for
      treatment planning. Advanced magnetic resonance imaging techniques, such as
      diffusion, perfusion, susceptibility weighted imaging, and magnetic resonance
      spectroscopy, enhance the imaging differences between these two pathologies.
      However, despite the utilization of these advanced techniques, the pathologic
      process may be confound by atypical findings. Here, we report a case of an
      autistic patient with multiple brain lesions with diffusion weighted imaging,
      susceptibility weighted imaging, and perfusion patterns resembling features of a
      multicentric glioblastoma, which were confirmed surgically, neuropathologically,
      and bacteriologically as brain abscesses. We discuss the differentiation of these
      different entities in the light of advanced magnetic resonance imaging
      techniques.

PMID- 28491191
TI  - Internal carotid artery dissection and pseudoaneurysm formation with resultant
      ipsilateral hypoglossal nerve palsy.
AB  - Craniocervical artery dissection is a potentially disabling condition caused by
      an intimal tear allowing blood to enter and dissect the media in the cranial
      direction which can occur spontaneously or as a result of trauma. When the
      dissection extends toward the adventitia, it can form a protrusion from the
      weakened vessel wall called a pseudoaneurysm, which may become a nidus for distal
      thromboembolism or cause mass effect on adjacent structures. Accurate and prompt
      diagnosis is critical as timely treatment can significantly reduce the risk of
      complications such as stroke. Here, we present a case of cervical ICA dissection
      and pseudoaneurysm formation causing mass effect with resultant compressive
      ipsilateral hypoglossal nerve palsy.

PMID- 28491192
TI  - A case report of spinal dural arteriovenous fistula: origins, determinants, and
      consequences of abnormal vascular malformations.
AB  - A spinal dural arteriovenous fistula is an abnormally layered connection between
      radicular arteries and venous plexus of the spinal cord. This vascular condition
      is relatively rare with an incidence of 5-10 cases per million in the general
      population. Diagnosis of spinal dural arteriovenous fistula is differentiated by
      contrast-enhanced magnetic resonance angiography or structural magnetic resonance
      imaging, but a definitive diagnosis requires spinal angiography methods. Here, we
      report a case of a 67-year-old female with a spinal dural arteriovenous fistula,
      provide a pertinent clinical history to the case nosology, and discuss the
      biology of adhesive proteins, chemotactic molecules, and transcription factors
      that modify the behavior of the vasculature to possibly cause sensorimotor
      deficits.

PMID- 28491193
TI  - Indium-111 labeled leukocyte accumulation in extremity soft tissue sarcoma.
AB  - Nuclear medicine labeled leukocyte whole-body scintigraphy is commonly used to
      identify a source of infection in a patient with fever of unknown origin. White
      blood cells can also localize to other sites of inflammation, including sometimes
      tumors. A patient with a large myxofibrosarcoma in his left forearm was scanned
      due to chronic low-grade fever and persistent leukocytosis. This case
      demonstrates focal white blood cell activity in an extremity soft tissue sarcoma.

PMID- 28491194
TI  - Leptomeningeal carcinomatosis and bilateral internal auditory canal metastases
      from ovarian carcinoma.
AB  - Ovarian cancer, a leading cause of death in women, typically spreads locally and
      rarely metastasizes to the brain or seeds the leptomeninges. We present a case of
      a 62-year-old woman with a history of treated ovarian cell carcinoma who
      developed bilateral sensorineural deafness and right-sided facial weakness and on
      imaging was found to have bilateral internal auditory canal (IAC) masses and
      leptomeningeal carcinomatosis, pathologically proven by cerebrospinal fluid
      cytology. We discuss her magnetic resonance imaging and positron emission
      tomography-computed tomography findings and review the imaging characteristics of
      IAC metastases. Finally, we review the literature on leptomeningeal
      carcinomatosis from ovarian cancer and discuss the high incidence of bilateral
      IAC metastases in patients with leptomeningeal carcinomatosis.

PMID- 28491195
TI  - Pediatric jugular vein aneurysm (phlebectasia): report of two cases and review of
      the literature.
AB  - Jugular vein aneurysms are rare vascular abnormalities that are most commonly
      encountered in the pediatric population. We report two separate cases in infants,
      both of whom presented with enlarging neck masses and were found to have jugular
      vein aneurysms. Diagnosis was established with duplex ultrasonography, computed
      tomography angiography, digitally subtracted catheter venography, and magnetic
      resonance imaging in one case and magnetic resonance imaging with magnetic
      resonance angiography/magnetic resonance venography, gray scale ultrasonography,
      and digital subtraction catheter venography in the other case. Both aneurysms
      were treated by surgical resection.

PMID- 28491196
TI  - Cerebral palsy and seizures in a child with tubulinopathy pattern dysgenesis and
      focal cortical dysplasia.
AB  - A 7-year-old boy with a history of spasticity, global developmental delay, and
      seizures was given the general diagnosis of cerebral palsy at an early age.
      Chromosomal array analysis performed at an outside center was normal. The
      patient's family sought neurodevelopmental pediatric care at a new institution
      following a move out of state. Electroencephalography confirmed abnormal
      epileptogenic activity. Brain magnetic resonance imaging showed findings
      consistent with a tubulin gene defect (tubulinopathy) and of focal cortical
      dysplasia, as well as evidence of a remote occipital lobe injury. This case
      report describes the various brain magnetic resonance findings suggestive of a
      tubulin gene defect and raises the possibility of focal cortical dysplasia
      manifesting as a result of tubulin dysfunction.

PMID- 28491197
TI  - Traumatic rupture of a giant congenital splenic cyst presenting as peritonitis.
AB  - Splenic cysts are uncommon, with large cysts and complications being rare. We
      describe a 6-year-old patient who initially presented 1 day after falling onto
      her abdomen at the playground with worsening abdominal pain and distention. An
      ultrasound of the abdomen demonstrated free abdominal fluid in all four
      quadrants. A subsequent contrast-enhanced computed tomography scan of the abdomen
      and pelvis was performed which showed a large splenic cyst with open
      communication to the peritoneal cavity. A congenital primary cyst was confirmed
      on pathology after partial splenectomy was performed. Although the majority of
      splenic cysts are asymptomatic, rupture can lead to acute peritoneal signs and
      mimic other significant causes of abdominal pain such as viscous injury or acute
      appendicitis.

PMID- 28491198
TI  - Synovial osteochondromatosis in a 14-year-old boy with a history of Legg-Calve
      Perthes disease.
AB  - We describe a case of a 14-year-old boy with a history of Legg-Calve-Perthes
      disease diagnosed at the age of 6 years and development of synovial
      osteochondromatosis of the same hip joint 7 years later. Synovial
      osteochondromatosis is very rare in children, and to the best of our knowledge,
      only a single case of Legg-Calve-Perthes disease and secondary synovial
      osteochondromatosis was described in the literature in a 35-year-old male, making
      this the first reported case of Legg-Calve-Perthes disease with development of
      synovial osteochondromatosis in a pediatric patient.

PMID- 28491199
TI  - Emergent sclerotherapy of a newborn with expanding lymphatic malformation causing
      respiratory distress.
AB  - The present report describes a case of acute airway obstruction in a newborn
      caused by an expanding hemorrhagic macrocystic lymphatic malformation (LM), which
      was successfully treated with emergent decompression and interventional radiology
      guided sclerotherapy. The use of sclerotherapy for macrocystic LMs has been well
      described for various indications. The urgent interventional treatment obviated
      the need for a tracheostomy. This case describes the rapid diagnosis and use of
      sclerotherapy in a large expanding macrocystic LM.

PMID- 28491200
TI  - Aneurysmal angiosarcoma associated with vascular graft revealed by 18F-FDG-PET
      imaging.
AB  - We report a rare case of vascular graft-associated aneurysmal angiosarcoma by 18F
      Fluorodeoxyglucose (FDG) positron emission tomography (PET). An 81-year-old male
      patient, with a prior history of graft interposition 1 year previously, was
      referred to 18F-FDG-PET because of an inflammatory syndrome of unknown origin.
      FDG-PET images revealed a particular pattern of intense circular uptake within
      the arterial wall (SUVmax = 10) in a popliteal aneurysm and, additionally, a
      large hypermetabolic mass centered by the graft. Remote hypermetabolisms in lung
      nodules and pleural thickenings were also detected. The diagnosis of angiosarcoma
      was ascertained through histopathological analysis of surgical samples.
      Development of an aneurysmal angiosarcoma at the site of a vascular graft is a
      rare entity, often misdiagnosed. 18F-FDG-PET appears to be useful in its
      detection with a PET pattern of intense circular uptake within the arterial wall.
      Such finding should lead to the search for distant metastasis.

PMID- 28491201
TI  - The advantage of iron-containing fiducial markers placed with a thin needle for
      radiotherapy of liver cancer in terms of visualization on MRI: an initial
      experience of Gold Anchor.
AB  - Radiotherapy for liver malignancy is increasing due to advances in radiotherapy
      technique. Visualization of the tumor as well as fiducial markers is essential.
      To see if improved visibility exists on computed tomography (CT) and magnetic
      resonance imaging (MRI), we evaluated an iron-containing fiducial marker. A
      patient with hepatocellular carcinoma and a patient with cholangiocarcinoma were
      enrolled. Pain caused by placement of marker and the best MRI sequence for
      visualization of both the fiducial marker as well as the liver tumor on MRI was
      evaluated. CT was obtained in 2.5-mm thickness, and MRIs were obtained in eight
      sequences (ie, T2-weighted image). 22G preloaded needles were used for marker
      placement in both patients; this caused little pain during placement under local
      anesthesia with xylocaine. No complication occurred in either patient. Both
      markers and tumors were well visualized by the same MRI sequence. The iron
      containing fiducial marker is safe and useful for detecting fiducial markers in
      the liver and for registration using CT and MRI.

PMID- 28491202
TI  - Just a mirage: heterotopic intrauterine and twin ectopic pregnancy mimicked by
      mirror imaging on ultrasound.
AB  - Heterotopic pregnancies are rare and are usually diagnosed by transvaginal
      ultrasound. Despite the routine use of sonography in early pregnancy, artifact
      created by mirror imaging can drastically and erroneously alter medical decision
      making by interfering with image interpretation. A heterotopic pregnancy with a
      single intrauterine gestation and twin left adnexal ectopic gestational sacs was
      observed on ultrasound in a woman presenting with abdominal pain. During
      laparoscopy, an ectopic pregnancy was not identified, and subsequent
      intraoperative ultrasound reproduced the heterotopic pregnancy through
      manipulation of bowel, confirming mirror image artifact. This phenomenon is
      rarely seen in obstetric imaging; therefore, lack of awareness can lead to false
      diagnosis of heterotopic pregnancy. Techniques to verify correct diagnosis should
      be used to resolve potential mirror artifact before proceeding with surgical
      management.

PMID- 28491203
TI  - Traumatic lumbar vertebral ring apophysis fracture with disk herniation in an
      adolescent.
AB  - We present a case of a 15-year-old male with history of back pain and bilateral
      lower limb radiculopathy due to fall. The magnetic resonance imaging scan showed
      disc bulge at L2-L3 level causing compression on contained nerve roots. In this
      case, computed tomography scan was indispensable for diagnosis and classification
      of the vertebral apophyseal fracture and to guide appropriate further management.
      Apophyseal ring fracture is an uncommon cause of back pain with radiculopathy in
      adolescents and athletes. High degree of suspicion is necessary to differentiate
      these injuries from disc herniation so as to further guide appropriate
      conservative or surgical management. The common cause of back pain in this
      population is related to musculoskeletal injuries. Lumbar disc herniation
      contributes to negligible number of cases in this age group, as against that seen
      in the adult population. An important and rare etiology to be considered for
      these patients includes vertebral ring apophyseal fracture.

PMID- 28491204
TI  - Being forced to become your own Doctor - Men who have Sex with Men's Experiences
      of Stigma in the Tanzanian Healthcare System.
AB  - OBJECTIVE: To acquire a deepened understanding of how stigma in healthcare
      affects health-seeking behaviours of same-sex practising men in Tanzania.
      METHODS: In-depth interviews with twelve men were conducted in Dar es Salaam,
      2012. Data were interpreted through qualitative content analysis. RESULTS:
      Narratives revealed that men's healthcare perceptions were shaped by previous
      encounters, rumours in gay community, norms and legislation around homosexuality.
      Fears of exposure aggravated men's possibilities of giving full anamnesis and
      detached them from formal healthcare services. CONCLUSIONS: Stigma in healthcare
      might lead to severe public health problems due to perceived exclusion from the
      health system by sexual minorities.

PMID- 28491205
TI  - Food Insecurity among American Indians and Alaska Natives: A National Profile
      using the Current Population Survey-Food Security Supplement.
AB  - Food insecurity increases the risk for obesity, diabetes, hypertension, and
      cancer-conditions highly prevalent among American Indians and Alaska Natives
      (AI/ANs). Using the Current Population Survey Food Security Supplement, we
      analyzed the food insecurity trends of AI/ANs compared to other racial and ethnic
      groups in the United States from 2000 to 2010. From 2000 to 2010, 25% of AI/ANs
      remained consistently food insecure and AI/ANs were twice as likely to be food
      insecure compared to whites. Urban AI/ANs were more likely to experience food
      insecurity than rural AI/ANs. Our findings highlight the need for national and
      tribal policies that expand food assistance programs; promote and support
      increased access to healthy foods and community food security, in both rural and
      urban areas; and reduce the burden of diet-related disparities on low-income and
      racial/ethnic minority populations.

PMID- 28491206
TI  - Effects From a Randomized Control Trial Comparing Researcher and School
      Implemented Treatments With Fourth Graders With Significant Reading Difficulties.
AB  - This study examined the effectiveness of a researcher-provided intervention with
      4th-graders with significant reading difficulties. The intervention emphasized
      multi-syllable word reading, fluent reading of high frequency words and phrases,
      vocabulary, and comprehension. To identify the participants, 1,695 fourth grade
      students were screened using the Gates MacGinitie Reading Test, and those whose
      standard score was 85 or lower were included in the study (N=485). Participants
      were randomly assigned (2:1) to receive either researcher-provided intervention
      (n=324) or intervention provided by school personnel (business as usual, BAU)
      (n=161). Findings revealed no statistically significant differences between
      students in the researcher-provided intervention and BAU groups. Using effect
      sizes as an indicator of impact, students in the researcher implemented treatment
      generally outperformed students in the school implemented treatment (BAU).
      Examining growth in standard scores, both groups made significant gains in
      reading outcomes with standard score growth from pretest to posttest of 3
      standard score points on decoding, 5 on fluency,, and 2.0 to 7 standard score
      points on reading comprehension measures.

PMID- 28491207
TI  - Giant laryngeal polyp: an unusual indication of tracheostomy.

PMID- 28491209
TI  - [Post-traumatic vertebral dissection: MRI results].

PMID- 28491208
TI  - Joint pain epidemiology and analgesic usage in Madagascar.
AB  - INTRODUCTION: To describe the epidemiology of joint pains and document analgesics
      usage in an African context. METHODS: Patients suffering from joint pain were
      recruited from nine sites located in Antananarivo, Madagascar, including 6
      hospital services and 3 clinics. Doctors collected information on the etiology
      and characteristics of the patients' pain. Analgesics prescribed by these doctors
      were also documented. RESULTS: In total, 400 patients were enrolled in the study
      (52.5% women, mean age of 42.34 years +/- 17.7 [4-86]). Pain of mechanical type
      was found in 260 participants, 65%; 95% CI [60.1% to 69.6%] and inflammatory type
      pains in 128 cases 32%; 95% CI [27.5% to 36.9%]. Mixed pains were found in 12
      patients (3%). The median duration of pain prior to the consultation was 6.5
      days. The average pain intensity was 57.9 +/- 19.9 mm of a total of 100 mm
      maximum on a visual analogue scale, VAS. The etiologies of mechanical type pains
      were dominated by fracture, common low back pain and tendonitis. Arthrosis was
      the dominant cause of inflammatory type pain, followed by rheumatoid arthritis
      and gout. NSAIDs (74.5%) were the most frequently prescribed analgesics followed
      by paracetamol (49.5%), weak opioids (23%) and corticosteroids (12.25%). Two
      thirds of medical prescriptions (65.3%) were of combined analgesics. CONCLUSION:
      These findings demonstrated that mechanical type pains were the main reason for
      consultations for joint pain in these situations in Antananarivo, Madagascar. The
      most frequently prescribed pain-relieving medications were NSAIDs, paracetamol,
      weak opioids and corticosteroids. This descriptive study may be a useful starting
      point for further epidemiological studies of pain in the African context.

PMID- 28491210
TI  - [Surgical treatment of the humeral pallet fractures in adults].
AB  - The treatment of humeral pallet fractures is mainly based on reconstruction
      surgery with osteosynthesis. We collected the data of 40 patients with humeral
      pallet fracture from our archives in the Department of Orthopaedics and
      Traumatology at the Ibn Sina University Hospital, Rabat from january 2012 to
      december 2014. The aim of our study was to highlight the clinical, therapeutic
      and evolutionary features of these fractures as well as the challenges in
      managing these complex fractures and in evaluating the results. There was a clear
      male predominance (75% of cases) with an average age of 35 years. Etiologies were
      dominated by road accidents (56%). All our patients had an emergency hospital
      admissions and underwent surgery. Type C fracture, according to MULLER and
      ALLGOWER (A.O) classification was the most frequent: 62.5% of cases. Associated
      lesions were fairly frequent (52.5%) in polytraumas. All our patients underwent
      surgery (100% of cases), via posterior border in 70% of cases. This procedure
      included reduction and then osteosynthesis using a Lecestre-type plate in 82.5%
      of the cases. Our results were good and average in 85.5% of cases, according to
      literature data. The management of this type of fracture is based on perfect
      anatomic reduction, a solid assembly which should allow an early reeducation
      resulting in good functional result.

PMID- 28491212
TI  - An unusual cause of chronic low back pain: ochronosis.

PMID- 28491211
TI  - [Rickettsiosis associated with cerebral infarction: a new case study].
AB  - Mediterranean spotted fever (MSF) is a rickettsiosis of the spotted fever group
      caused by rickettsia conorii. This zoonosis is benign but it can be complicated
      by severe neurological impairment (hence its severity). We report the case of a
      49-year old patient hospitalized in the Department of Dermatology for
      rickettsiosis, who suffered from right massive hemiplegia of brutal onset.
      Magnetic resonance angiography (MRA) of the brain showed deep left sylvian
      fissure ischemic stroke. The diagnosis of conorii-type rickettsiosis has been
      retained based on the aspect of skin lesions and on positive sierologic testing
      with the indirect immunofluorescence method. Evolution was favorable under anti
      biotherapy (Doxycycline and fluoroquinolone). Cerebral infarction, exceptionally
      reported in the framework of neurological manifestations of rickettsioses, is a
      complication that shouldn't be underestimated especially when etiologic
      assessment (cardiovascular in particular) is negative.

PMID- 28491213
TI  - [The diffuse plexiform neurofibroma of the left thigh in a patient aged 78 years
      in dermatological environment in Bamako].

PMID- 28491214
TI  - Prescribing pattern of psychotropic medications in child psychiatric practice in
      a mental referral hospital in Botswana.
AB  - INTRODUCTION: There is a growing preference for psycho-pharmacological therapy
      over non-pharmacological care. The prescription pattern and the choice of
      psychotropic medications vary in different settings. Whilst newer agents and
      rational prescribing are favored in the more specialized settings, the pattern
      remains unclear in less specialized units, largely due to lack of data. The aims
      were to conduct a treatment audit in the only mental referral hospital in
      Botswana, which is a non-specialized child and adolescent care setting and see
      how it conforms to best practice. METHODS: A retrospective audit which involved
      the extraction of socio-demographic and clinical information from the records of
      patients who were <= 17 years and seen from January 1, 2012-July 31, 2016.
      RESULTS: A total of 238 files were used for this report. Mean age (SD) was 12.41
      (4.1) years. Of the 120 (50.4%) patients who had pharmacological intervention,
      only 85(70.8%) had monotherapy. The most commonly prescribed psychotropic agents
      were antipsychotics (40%). Off-label use of antipsychotics and polypharmacy were
      31.2% and 29.2% respectively. CONCLUSION: The level of conformity to standard
      practice in terms of psychotropic prescribing in our setting is consistent with
      the reports from developed countries where more specialized care ostensibly
      exists. Further studies will be necessary to determine the scope of psychotropic
      use.

PMID- 28491215
TI  - Clinical outcomes of posterior spinal stabilization with rigid vertical strut and
      spinal process wires (the Adeolu's technique) in a developing country.
AB  - INTRODUCTION: Conventional instrumentation for spinal stabilization is beyond the
      reach of many patients in developing countries. A low-cost and easily-available
      method of spinal stabilization using vertical struts and spinal process wires
      (Adeolu's technique) was recently introduced in Nigeria. We describe the clinical
      outcomes of a prospective series of patients managed using the technique.
      METHODS: From 2011 to 2012, we performed posterior spinal stabilization in
      eighteen patients using the technique. Primary outcomes were radiological
      evidence of rigid stabilization and mobilization without restrictions referable
      to the procedure in the immediate post-operative period. Implant rotation,
      migration, back-out, fracture, wound infection, worsening neurological status and
      need for implant removal were secondary measures. Overall patient satisfaction
      was assessed using a five-point Likert scale. The average follow-up period was
      11.6 months. RESULTS: The average age of the patients was 45.8 years. Trauma with
      unstable spinal fractures (11), spondylosis (5), and thoracic extra-dural tumour
      (2) were the indications for surgery. The average number of spinal levels
      stabilized was 6. All patients had satisfactory primary outcomes. Implant
      rotation occurred in 3 patients (16.7%). There was no case of implant migration,
      back-out or fracture. Superficial surgical site infection occurred in one
      patient. There was no need to remove the implant in any subject and none had post
      operative worsening of neurological status. The overall patient satisfaction was
      good with 17 patients (94.4%) reporting "highly satisfied" or "satisfied" with
      the surgical procedure. CONCLUSION: The technique offers utility in a wide range
      of spinal pathologies and short-term clinical outcomes are good.

PMID- 28491216
TI  - [Isolated tuberculous trochanteritis].

PMID- 28491217
TI  - [Guillain Barre syndrome and diabetic acido-ketotic decompensation during
      pregnancy: a case report and review of the literature].
AB  - A 27-year-old pregnant woman was admitted to the resuscitation department with
      severe spontaneous acute ketoacidosis as early symptom of type 1 diabetes. The
      patient underwent resuscitation and insulin treatment with good clinical and
      biological evolution. On day 4, the patient had polyradiculoneuritis
      characterised by acute onset. Additional emergency examinations were negative.
      Lumbar cytopunction showed albuminocytologic dissociation. Electromyogram
      confirmed the diagnosis of Guillain Barre syndrome (GBS). The patient was treated
      with veinoglobulin and underwent physical rehabilitation. A dramatic improvement
      in neurological signs was noted. With regard to pregnancy, the patient aborted a
      week after being diagnosed with GBS. The association of GBS with ketotic
      decompensation is rare. Indeed, a few cases have been reported in the literature.
      This association during pregnancy was never described, hence the originality of
      this case study.

PMID- 28491218
TI  - Bacterial agents of the discharging middle ear among children seen at the
      University of Nigeria Teaching Hospital, Enugu.
AB  - INTRODUCTION: Discharging middle ear continues to be one of the commonest
      problems seen in the developing world. There is an ever growing need to carry out
      studies periodically to determine the common bacterial agents responsible for
      discharging otitis media and their antibiotic sensitivity especially in set-ups
      characterized with minimal laboratory services. The study sought to determine the
      common bacterial agents causing discharging middle ear among children presenting
      at the University of Nigeria Teaching Hospital, Enugu and their sensitivity to
      the commonly available antibiotics. METHODS: Middle ear swabs were collected from
      100 children aged 1 month to 17 years at the Children Out-Patient and
      Otorhinolaryngology Clinics of the University of Nigeria Teaching Hospital,
      Enugu, Nigeria. The specimens were cultured for aerobic bacterial organisms and
      their sensitivity determined. RESULTS: Among those with acute discharge,
      Staphylococcal aureus was isolated in 31.3% and Proteus species in 25.0%. In
      chronically discharging ears, Proteus Species dominated (39.1%), followed by
      Staphylococcal aureus (28.3%). CONCLUSION: Staphylococcal aureus and Proteus
      species were the commonest bacterial agents in acute and chronic otitis media
      respectively. Most isolates showed high sensitivity to the fluoroquinolone
      antibiotics.

PMID- 28491219
TI  - [A non-EDTA-dependent pseudothrombocytopenia: about a case].
AB  - Pseudothrombocytopenia is a rare phenomenon in laboratory explained by in vitro
      agglutination of platelets. Microscopic examination of the peripheral blood smear
      is of key importance to confirm the diagnosis and to avoid any inappropriate or
      dangerous clinical and therapeutic decision. Its occurrence in a patient, under
      treatment with heparin, raises the problem of differential diagnosis of heparin
      induced thrombocytopenia. The aim of this study was to eliminate any confusion
      between this purely artefactual phenomenon and heparin-induced thrombocytopenia.

PMID- 28491221
TI  - Isolated tuberculosis of metacarpal bone in a 3 year-old child.
AB  - Primary tuberculosis osteomyelitis of metacarpal bone is rare. The majority of
      cases occur in children and young adults and there is difficulty in diagnosis
      mainly in young children. We report a new case in children aged of 3 years,
      presenting a swelling on the dorsal side of her right hand since 8 months. X-ray
      showed an expansile, cystic and lytic lesion involving the little finger
      metacarpal. Tuberculosis was confirmed on histological examination. No lesions in
      lung parenchyma or lymphadenopathy were associated. Patient was successfully
      managed by anti-tubercular drugs.

PMID- 28491220
TI  - A primary intestinal lymphangiectasia hiding the diagnosis of pleural and
      pericardial tuberculosis: a clinical observation.
AB  - Primary intestinal lymphangiectasia (Waldmann's disease) is an exudative
      enteropathy characterized by lymph leakage into the small bowel lumen leading to
      hypoalbuminemia, hypogammaglobulinemia and lymphopenia (particularly T-cell). The
      diagnosis is based on viewing the duodenal lymphangiectasia. A 20 years old
      female patient, treated for a primary intestinal lymphangiectasia, has consulted
      for anasarca. Etiological work-up reveals pleural and pericardial tuberculosis.
      The clinical aggravation of an enteropathy, particularly in adulthood, requires a
      search for a secondary etiology. Tuberculosis should be sought systematically.

PMID- 28491222
TI  - [Intramedullary glioblastomas in the child: location and rare histologic type].

PMID- 28491223
TI  - [Neuroendocrine carcinoma of the bladder: about 5 cases].
AB  - Neuroendocrine carcinoma of the bladder is a rare histological entity,
      characterized by the ability to metastasize quickly and associated with a poor
      prognosis. The purpose of this study was to analyze the clinical, histological,
      therapeutic and prognostic characteristics of neuroendocrine carcinoma of the
      bladder. We conducted a retrospective study collecting data from the medical
      records of 5 patients in the Department of Urology, at the Ibn Sina University
      Hospital during the period between January 2008 and June 2015. The average age
      was 63 years. Four males and one female were involved in the sudy. The
      neuroendocrine carcinoma was pure in four cases and impure or associated with
      urothelial component in one case. In two patients metastases were present at
      initial diagnosis. In one case, cystectomy was performed followed by neoadjuvant
      chemotherapy; chemoradiotherapy was performed in two cases and palliative
      chemotherapy in the other two cases. The median survival was 10 months. Only one
      patient was alive, with a follow-up period of 20 months. The management of
      neuroendocrine carcinoma of the bladder is not standardized, several therapeutic
      options have been proposed: surgery, radiation therapy and chemotherapy.

PMID- 28491224
TI  - [Macrophage activation syndrome complicating family lymphohistiocytosis].
AB  - Macrophage activation syndrome (MAS) is an anatomoclinic entity due to
      inappropriate macrophage activation. It is a rare pathology, characterized by
      clinical signs that are not very specific and by biological elements. Their
      association must evoke the diagnosis. It can be classified as primary or
      secondary, its prognosis is still unclear. We report the case of a 3-year and 4
      month-old infant admitted to our department with primary MAS in order to remind
      clinicians the importance of suspecting primary cause in specific situations.

PMID- 28491225
TI  - ?

PMID- 28491226
TI  - [A rare etiology of horse tail syndrome: neuro-aggressive vertebral hemangioma].

PMID- 28491227
TI  - [A rare cause of spinal cord compression: spontaneous spinal epidural hematoma].

PMID- 28491228
TI  - [Survival among chronic hemodialysed patient in Cameroon].
AB  - INTRODUCTION: Haemodialysis is the only renal replacement therapy available in
      Cameroon; 95% of patients has received subsidies by the State since 2002 and the
      number of dialysis centers is growing. However, since the opening of the first
      center in 1990, there are no data on survival in chronic dialysis patients.
      METHODS: We conducted a multicenter prospective cohort study of 15 months in
      order to assess mortality rates and factors that influence the survival of
      chronic hemodialysis patients in Cameroon. RESULTS: We followed 197 patients of
      whom 109 were incident patients. The average age was 47,97+/- 13.19 years and 55%
      were male. The mean duration of dialysis in prevalent patients was 12.5 months.
      The mortality rate was 57,58%, 50% of which occurred the first 3 months and
      abandonment rate was 8.6%. Uremia and catheter-related sepsis were the main
      causes of death. At a median follow up of 15 months, the overall survival was
      30.77%, with an average duration of life of 8 months. Prevalent patients,
      patient's place of residence where the dialysis center is located, nonfamily
      management, predialysis follow up > 3 months, blood cholesterol when patient
      first started on dialysis> 1.5g/l, a mental test score > 25 were associated with
      a better survival. CONCLUSION: In Cameroon, mortality rate in hemodialysis
      patients is high, with a mean survival time of 8 months; most patients die within
      the first 3 months.

PMID- 28491229
TI  - [Anti-VEGF therapy for juxtafoveolar choroidal neovessels in people with high
      myopia: about a case].
AB  - Choroidal neovessels are a threatening complication of high myopia, accounting
      for 5 to 10% of cases. They require immediate treatment because of their poor
      prognosis. Anti-VEGF intravitreal injections are currently a new therapeutic
      alternative far exceeding photodynamic therapy (PDT). Nevertheless, anti-VEGF
      treatment algorithm for this type of neovessels remains a matter of discussion
      among the authors. The purpose of this study was to highlight the difficulties in
      managing these neovessels and to discuss the Anti-VEGF therapeutic regimen to
      follow.

PMID- 28491230
TI  - Lung hemorrhage and brain stroke following fatal viper (cerastes cerastes) bite.

PMID- 28491231
TI  - Monoarthritis of the knee revealing tabetic arthropathy.

PMID- 28491232
TI  - [Cavernoma in the fourth ventricle].

PMID- 28491233
TI  - Branchial cleft cyst: a case report.

PMID- 28491234
TI  - Knowledge and utilization of contraceptive devices among unmarried undergraduate
      students of a tertiary institution in Kano State, Nigeria 2016.
AB  - INTRODUCTION: Students in the universities mostly live independently from their
      parents or guardians, some of them for the first time. This gives them freedom
      and opportunity for high risk behavior such as unplanned and unprotected sex. The
      results of such sexual experimentation may include unplanned and or unwanted
      pregnancies that may lead to unsafe abortions and sexually transmitted infections
      (STIs) including HIV/AIDS. Contraception has the potential to prevent unwanted
      pregnancies, abortion, and STIs. This study aimed at assessing the general
      knowledge on contraceptives, sexual practices, and level of utilization of
      contraceptives devices among unmarried students of the Bayero University Kano.
      METHODS: We did an institutional based cross-sectional descriptive study. We
      administered a pretested, self-administered, structured questionnaire to randomly
      selected unmarried undergraduate students of the institution. We analyzed data
      using Microsoft Excel 2016 and Epi-info7. RESULTS: A total of 300 students were
      interviewed. The median age for respondents was 23 years with an age range of 16
      25 years. Male respondents made up 61.3% (184) while the females made up the
      remaining 38.7% (116). Also, 158(47.33%) of respondents lived outside the school
      campus, while 158(52.67%) lived in the school hostels. Knowledge on contraception
      was 87.7% among respondents with internet (91%) and media (89.3%) as the
      commonest sources of knowledge. Proportion of sexually active students was
      10.67%, while prevalence of contraceptive utilization among sexually active
      students was 15.63%. About 8(25%) had their sexual debut at < 16years of age,
      22(68.75%) at ages between 16-20years, and 4(12.5%) above 20years of age. All
      sexually active respondents practice vaginal sex. Most sexual debuts were planned
      (44.75 %) and with friends (86.4%), and they occurred between the ages of 16
      20years age group in 70.3% of respondents. CONCLUSION: Even though knowledge on
      contraceptive used was high among the respondents, utilization of contraceptives
      among sexually active students was low, thus creating a window for possible
      unintended and unwanted pregnancies among these group of students.

PMID- 28491235
TI  - A systematic review of physical activity policy recommendations and interventions
      for people with mental health problems in Sub-Saharan African countries.
AB  - INTRODUCTION: There is a need for interventions to address the escalating mental
      health burden in Sub-Saharan Africa (SSA). Implementation of physical activity
      (PA) within the rehabilitation of people with mental health problems (PMHP) could
      reduce the burden and facilitate recovery. The objective of the current review
      was to explore (1) the role of PA within mental health policies of SSA countries,
      and (2) the current research evidence for PA to improve mental health in SSA.
      METHODS: We screened the Mental Health Atlas and MiNDbank for mental health
      policies in SSA countries and searched PubMed for relevant studies on PA in PMHP
      in SSA. RESULTS: Sixty-nine percent (=33/48) of SSA countries have a dedicated
      mental health policy. Two of 22 screened mental health policies included broad
      physical activity recommendations. There is clear evidence for the role of PA in
      the prevention and rehabilitation of depression in SSA. CONCLUSION: Despite the
      existing evidence, PA is largely a neglected rehabilitation modality in the
      mental health care systems of SSA. Continued education of existing staff,
      training of specialized professionals and integration of PA for mental health in
      public health awareness programs are needed to initiate and improve PA programs
      within the mental health care systems of SSA.

PMID- 28491236
TI  - Self-referral patterns among federal civil servants in oyo state, South-Western
      Nigeria.
AB  - INTRODUCTION: Primary health care is widely accepted as the first point of care;
      yet, individuals requiring healthcare engage in self-referrals to higher levels
      of care thereby by-passing primary care. Little is known of the extent to which
      self-referrals are carried out when care is needed. This study thus sought to
      determine the prevalence of self-referral, its patterns and factors influencing
      self-referrals amongst federal civil servants in Southwestern Nigeria. METHODS: A
      cross-sectional study was carried out among 300 federal civil servants who were
      interviewed using validated and pre-tested interviewer-administered semi
      structured questionnaires. Data was analyzed using univariate and Chi-square test
      at level of significance set at P <0.05. RESULTS: Mean age of the respondents was
      39.96 +/- 9.1 years with majority being married (80.7%); 90.7% completed tertiary
      education (and 76.7 % were middle grade (7-12) level officers. Most (60.0%) of
      the respondents had ever engaged in self-referral. Malaria was the commonest
      health problem (39.7%) for self-referral to secondary or tertiary facilities.
      Desire for quality service (35.7%) and competent staff (35.2%) were the commonest
      reasons for self-referral to a higher level of health care. More female
      respondents (76.0%) compared to male respondents (64.0%) significantly engaged in
      self-referral (p = 0.02, X2 = 5.14). Respondents having good knowledge of
      referral practices engaged less in self-referral compared to those with poor
      knowledge. (p = 0.02, X2 = 5.43). CONCLUSION: Having good knowledge of referral
      practices and being male are positively associated with referral practices.
      Creating awareness and improving knowledge on referral practices with special
      emphasis on women population are desirable strategies for encouraging the use of
      primary health care as first of point of contact with health systems.

PMID- 28491237
TI  - Potential of Lichen Compounds as Antidiabetic Agents with Antioxidative
      Properties: A Review.
AB  - The advancement in the knowledge of potent antioxidants has uncovered the way for
      greater insight in the treatment of diabetic complications. Lichens are a rich
      resource of novel bioactive compounds and their antioxidant potential is well
      documented. Herein we review the antidiabetic potential of lichens which have
      received considerable attention, in the recent past. We have correlated the
      antidiabetic and the antioxidant potential of lichen compounds. The study shows a
      good accordance between antioxidant and antidiabetic activity of lichens and
      points out the need to look into gathering the scarce and scattered data on
      biological activities for effective utilization. The review establishes that the
      lichen extracts, especially of Parmotrema sp. and Ramalina sp. have shown
      promising potential in both antidiabetic and antioxidant assays. Ubiquitous
      compounds, namely, zeorin, methylorsellinate, methyl-beta-orcinol carboxylate,
      methyl haematommate, lecanoric acid, salazinic acid, sekikaic acid, usnic acid,
      gyrophoric acid, and lobaric acid have shown promising potential in both
      antidiabetic as well as antioxidant assays highlighting their potential for
      effective treatment of diabetic mellitus and its associated complications. The
      available compilation of this data provides the future perspectives and highlight
      the need for further studies of this potent herbal source to harvest more
      beneficial therapeutic antidiabetic drugs.

PMID- 28491238
TI  - Inhibition of miR-302 Suppresses Hypoxia-Reoxygenation-Induced H9c2 Cardiomyocyte
      Death by Regulating Mcl-1 Expression.
AB  - MicroRNAs play important roles in cell proliferation, differentiation, and
      apoptosis, and their expression influences cardiomyocyte apoptosis resulting from
      ischemia-induced myocardial infarction. Here, we determined the role of miR
      expression in cardiomyocyte apoptosis during hypoxia and reoxygenation. The rat
      cardiomyocyte cell line H9c2 was incubated for 3 h in normal or hypoxia medium,
      followed by reoxygenation for 24 h and transfection with a miR-302 mimic or
      antagomir. The effect of miR-302 on myeloid leukemia cell-differentiation protein
      1 (Mcl-1) expression was determined by western blot, real-time polymerase chain
      reaction, and luciferase reporter assays, with cell viability assays. We observed
      that miR-302 expression was elevated by hypoxia/reoxygenation injury and
      increased further or decreased by transfection of the miR-302 mimic or miR-302
      antagomir, respectively. Additionally, elevated miR-302 levels increased
      apoptosis-related protein levels and cardiomyocyte apoptosis, and luciferase
      reporter assays revealed miR-302 binding to the Mcl-1 mRNA 3' untranslated
      region. Our findings suggested that miR-302 overexpression aggravated
      hypoxia/reoxygenation-mediated cardiomyocyte apoptosis by inhibiting
      antiapoptotic Mcl-1 expression, thereby activating proapoptotic molecules.
      Furthermore, results indicating cardiomyocyte rescue from hypoxia/reoxygenation
      injury following treatment with miR-302 antagomir suggested that miR-302
      inhibition might constitute a therapeutic strategy for protection against
      cardiomyocyte apoptosis during hypoxia/reoxygenation injury.

PMID- 28491239
TI  - Opuntia spp.: Characterization and Benefits in Chronic Diseases.
AB  - Opuntia species have been used for centuries as food resources and in traditional
      folk medicine for their nutritional properties and their benefit in chronic
      diseases, particularly diabetes, obesity, cardiovascular diseases, and cancer.
      These plants are largely distributed in America, Africa, and the Mediterranean
      basin. Opuntia spp. have great economic potential because they grow in arid and
      desert areas, and O. ficus-indica, the domesticated O. species, is used as a
      nutritional and pharmaceutical agent in various dietary and value-added products.
      Though differences in the phytochemical composition exist between wild and
      domesticated (O. ficus-indica) Opuntia spp., all Opuntia vegetatives (pear,
      roots, cladodes, seeds, and juice) exhibit beneficial properties mainly resulting
      from their high content in antioxidants (flavonoids, ascorbate), pigments
      (carotenoids, betalains), and phenolic acids. Other phytochemical components
      (biopeptides, soluble fibers) have been characterized and contribute to the
      medicinal properties of Opuntia spp. The biological properties of Opuntia spp.
      have been investigated on cellular and animal models and in clinical trials in
      humans, allowing characterization and clarification of the protective effect of
      Opuntia-enriched diets in chronic diseases. This review is an update on the
      phytochemical composition and biological properties of Opuntia spp. and their
      potential interest in medicine.

PMID- 28491240
TI  - High quality permanent draft genome sequence of Chryseobacterium bovis DSM
      19482T, isolated from raw cow milk.
AB  - Chryseobacterium bovis DSM 19482T (Hantsis-Zacharov et al., Int J Syst Evol
      Microbiol 58:1024-1028, 2008) is a Gram-negative, rod shaped, non-motile,
      facultative anaerobe, chemoorganotroph bacterium. C. bovis is a member of the
      Flavobacteriaceae, a family within the phylum Bacteroidetes. It was isolated when
      psychrotolerant bacterial communities in raw milk and their proteolytic and
      lipolytic traits were studied. Here we describe the features of this organism,
      together with the draft genome sequence and annotation. The DNA G + C content is
      38.19%. The chromosome length is 3,346,045 bp. It encodes 3236 proteins and 105
      RNA genes. The C. bovis genome is part of the Genomic Encyclopedia of Type
      Strains, Phase I: the one thousand microbial genomes study.

PMID- 28491242
TI  - Moving Forward.

PMID- 28491241
TI  - Fifteen years of bone marrow mononuclear cell therapy in acute myocardial
      infarction.
AB  - In spite of modern treatment, acute myocardial infarction (AMI) still carries
      significant morbidity and mortality worldwide. Even though standard of care
      therapy improves symptoms and also long-term prognosis of patients with AMI, it
      does not solve the critical issue, specifically the permanent damage of
      cardiomyocytes. As a result, a complex process occurs, namely cardiac remodeling,
      which leads to alterations in cardiac size, shape and function. This is what has
      driven the quest for unconventional therapeutic strategies aiming to regenerate
      the injured cardiac and vascular tissue. One of the latest breakthroughs in this
      regard is stem cell (SC) therapy. Based on favorable data obtained in
      experimental studies, therapeutic effectiveness of this innovative therapy has
      been investigated in clinical settings. Of various cell types used in the clinic,
      autologous bone marrow derived SCs were the first used to treat an AMI patient,
      15 years ago. Since then, we have witnessed an increasing body of data as regards
      this cutting-edge therapy. Although feasibility and safety of SC transplant have
      been clearly proved, it's efficacy is still under dispute. Conducted studies and
      meta-analysis reported conflicting results, but there is hope for conclusive
      answer to be provided by the largest ongoing trial designed to demonstrate
      whether this treatment saves lives. In the meantime, strategies to enhance the
      SCs regenerative potential have been applied and/or suggested, position papers
      and recommendations have been published. But what have we learned so far and how
      can we properly use the knowledge gained? This review will analytically discuss
      each of the above topics, summarizing the current state of knowledge in the
      field.

PMID- 28491243
TI  - Choledochal cyst in pregnancy.
AB  - INTRODUCTION: Biliary diseases during pregnancy are not uncommon and are
      frequently due to cholelithiasis. Choledochal cyst during pregnancy is rare. The
      management of biliary pathologies during pregnancy poses a challenge as the
      window of opportunity to carry out any interventions with minimal risk is small.
      CASE REPORT: We report the case of a lady who was diagnosed with a large type I
      choledochal cyst during the second trimester of pregnancy. Due to increasing
      symptoms and recurrent cholangitis, she was managed with antibiotics and surgical
      resection. She remained well and delivered a healthy baby boy. CONCLUSION:
      Clinicians need to consider choledochal cyst as a differential in pregnant
      patients presenting with upper abdominal fullness.

PMID- 28491244
TI  - Diarrheagenic Escherichia coli pathotypes frequency in Khuzestan province of
      Iran.
AB  - BACKGROUND AND OBJECTIVES: Diarrheagenic Escherichia coli (DEC) is an emerging
      agent among pathogens that causes diarrhea. Studies showed that diarrheagenic E.
      coli such as enterohaemorrhagic E. coli (EHEC), enteroaggregative E. coli (EAEC),
      enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), enterotoxigenic
      E. coli (ETEC), diffusely adhering E. coli (DAEC) and shiga toxin producing E.
      coli (STEC) strains are among the most frequent causative agents in acute
      diarrhea. The aim of this study was to determine the frequency of DEC pathotypes
      in Khuzestan province. MATERIALS AND METHODS: Stool samples were collected from
      patients with diarrhea in Khuzestan province of Iran. E. coli strains were
      isolated using conventional culture and standard biochemical tests. The
      polymerase chain reaction (PCR) technique was used to detect presence of
      virulence genes, i.e; eae, stx1 and stx2 for EHEC, bfp and eae for EPEC, LT and
      ST for ETEC, AA for EAEC, invE for EIEC, stx1 and stx2 for STEC. RESULTS:
      Altogether, 200 stool samples were obtained from patients, of which 158 (79%)
      were positive for E. coli. DEC was identified in 127 (63%) of stool samples,
      which frequency of each pathotypes were as follows: atypical EPEC 49 (39%),
      typical EPEC 1 (0.7%), STEC 50 (39.3%), ETEC 21 (16.3%), EAEC 5 (4.0%) and EIEC 1
      (0.7%). Most frequent etiological agents of diarrhea in Khuzestan province of
      Iran were STEC and EPEC. CONCLUSION: Our findings showed DEC had been agent of
      diarrhea in Khuzestan. This finding provides evidence that effort should be made
      to estimate the burden of infection by the etiological agent for better medical
      approach and should raise notification about antibiotic resistance among
      bacterial infection.

PMID- 28491246
TI  - Significance of coagulase negative Staphylococcus from blood cultures: persisting
      problems and partial progress in resource constrained settings.
AB  - BACKGROUND AND OBJECTIVES: Coagulase negative Staphylococcus (CoNS) is frequently
      isolated from blood cultures but their significance is difficult to interpret.
      CoNS bacteria which are often previously dismissed as culture contaminants are
      attracting greater importance as true pathogens in the past decades. Clinical
      evaluation of these isolates suggests that although there is a relative increase
      of CoNS associated bloodstream infections in recent years, the microorganisms
      still remain the most common contaminants in blood cultures. The objective of
      this study was to determine the significance of CoNS isolated from blood
      cultures. MATERIALS AND METHODS: A retrospective study was conducted to evaluate
      the rate of contamination in blood cultures in a tertiary care hospital. The
      paired specimens of blood were cultured using conventional culture methods and
      the isolates of coagulase negative staphylococci were identified by standard
      methodology. Clinical data, laboratory indices, microbiological parameters and
      patient characteristics were analyzed. RESULTS: Of 3503 blood samples, CoNS were
      isolated from blood culture of 307 patients (8.76%). The isolates were reported
      as true pathogens of bloodstream infections in only 74 out of 307 cases (24.1%).
      In the vast majority, 212 of 307 (69.0%), they were mere blood culture
      contaminants and reported as insignificant/contaminant. CONCLUSION: Determining
      whether a growth in the blood culture is a pathogen or a contaminant is a
      critical issue and multiple parameters have to be considered before arriving at a
      conclusion. Ideally, the molecular approach is for the most part a consistent
      method in determining the significant isolates of CoNS. However, in countries
      with inadequate resources, species identification and antibiogram tests are
      recommended when determining significance of these isolates.

PMID- 28491245
TI  - Frequency evaluation of genes encoding siderophores and the effects of different
      concentrations of Fe ions on growth rate of uropathogenic Escherichia coli.
AB  - BACKGROUND AND OBJECTIVES: Bacteria need iron for growth and most of them can
      actively acquire Fe ions using especial iron-chelating proteins which named
      siderophores. We aimed to determine the frequencies of iucA, iroN and irp2 genes
      in the uropathogenic Escherichia coli (UPEC) isolates. We also analyzed the
      effects of siderophore genes beside iron supplements on growth rate of the
      isolates. MATERIALS AND METHODS: Totally, 170 E. coli strains were isolated from
      urinary tract infections and the presence of 3 siderophore genes were analyzed
      using PCR among them. Three final concentrations of 0.1, 0.5 and 1 mMFe(II) and
      Fe(III) ions were made in M9 broth medium. Inoculated cultures were incubated at
      37 degrees C for 33 hours and bacterial density in the suspension was measured
      with 1 hour intervals using spectrophotometer. RESULTS: The frequency of iucA,
      iroN and irp2 genes among 170 UPEC isolates were 29 (17.1%), 52 (30.6%) and 116
      (68.2%), respectively. In addition, Our findings showed that Fe(II) supplements
      had significantly higher promoting effects on UPEC growth rate almost in all of
      the three applied concentrations (0.1, 0.5 and 1 mM) compared to the control
      group (P<0.0001). Differences between Fe(III) supplemented groups and the
      controls were statistically significant when 1 mM concentration was added into
      the medium (p<0.05). CONCLUSION: irp2 gene probably plays a major role in the
      pathogenesis of UPEC strains. Promoting or inhibitory effects of iron on
      bacterial growth mainly depend on the iron concentration in the culture medium
      however different siderophores have different potentials for capturing and
      assimilation of Fe ions by the bacteria, especially inside the host cell.

PMID- 28491247
TI  - The antibacterial activity of methanolic Anacyclus pyrethrum and Pistacia
      lentiscus L. extract on Escherichia coli.
AB  - BACKGROUND AND OBJECTIVES: Antibiotic therapy is the main choice in treatment of
      Escherichia coli induced infections. Using herbal medication is an alternative
      choice in treatment of diseases. The aim of this study was to determine the
      antibacterial activity of two traditionally used herbs in Iranian medicine,
      Anacyclus pyrethrum and Pistacia lentiscus L., on Escherichia coli. MATERIALS AND
      METHODS: The antibacterial effect of methanolic extract of Anacyclus pyrethrum
      and Pistacia lentiscus L. were examined in disk diffusion and skipped wells
      methods by measuring the diameter of inhibition zones around wells containing
      different concentrations of extracts from (10-1000 mg/ml) using standard broth
      macrodilution, method the MIC and MBC were defined. RESULTS: The methanolic
      extract of Anacyclus pyrethrum from 300 to 1000 mg/ml and the methanolic extract
      of Pistacia lentiscus L. from 30 to 1000 mg/ml showed antibacterial activity on
      Escherichia coli. The MIC of Anacyclus pyrethrum and Pistacia lentiscus L.
      methanolic based extract were 800 and 1000 mg/ml, respectively. The MBC was
      achieved at 800 mg/ml for methanolic extract of Anacyclus pyrethrum and Pistacia
      lentiscus L. CONCLUSION: The methanolic extract of Anacyclus pyrethrum and
      Pistacia lentiscus L. have antibacterial effect on Escherichia coli bacteria.
      This activity is dose-dependent.

PMID- 28491248
TI  - The comparison of five low cost liquid formulations to preserve two phosphate
      solubilizing bacteria from the genera Pseudomonas and Pantoea.
AB  - BACKGROUND AND OBJECTIVES: Phosphorus is one of the low bioavailable
      macroelements. Use of microorganisms in biofertilizers could release phosphorus
      from insoluble compounds. Pseudomonas putida P13 and Pantoea agglomerans P5 are
      well recognized for application as phosphate solubilizing bioinoculants and are
      used as solid carrier based. Liquid bioinoculants are preferred for economizing
      production process and longer shelf-life. MATERIALS AND METHODS: Five low cost
      liquid formulations were examined. Formulations 1, 2 and 3, were phosphate
      buffer, 0.2% and 0.5% KNO3 dissolved in phosphate buffer, respectively.
      Formulation 4 was nutrient broth containing 4% glycerol and formulation 5 was
      diluted nutrient broth containing 4% glycerol. Survival (cfu) and phosphate
      solubilization index (SI) were evaluated after 3 months. RESULTS: Considering
      strain P5, increase in KNO3 concentration decreased preserving ability. While
      using KNO3 at 0.2% was accompanied with reaching maximum SI level. Overall, less
      nutritious formulations (1 and 5) provided maximum preserving ability without
      bioactivity loss. In the case of strain P13, maximum survival obtained in
      formulations 2 and 3, whereas SI level decreased. Preserving ability in
      formulations 1, 4 and 5 was similar but less nutritious formulations (1 and 5),
      improved bioactivity. CONCLUSION: The results introduced two formulations of 1
      and 5 as economically efficient liquid bioinoculants for Pseudomonas putida and
      Pantoea agglomerans.

PMID- 28491249
TI  - The seroprevalence of Mycoplasma pneumoniae IgM and IgG antibodies in patients
      with ischemic stroke.
AB  - BACKGROUND AND OBJECTIVES: Association between Mycoplasma pneumoniae infection
      and increased risk for brain stroke has been well understood. Hence, the value of
      serologic tests for assessing causative relationship between this infection and
      brain stroke seems to be high. The present study aimed to determine serum level
      of anti-Mycoplasma pneumoniae antibodies in patients with brain stroke and to
      compare it with non-stroke patients. MATERIALS AND METHODS: This cross-sectional
      study was performed on 97 consecutive ischemic stroke patients and 97 sex and age
      matched non-stroke patients. Quantitative enzyme-linked immunosorbent assay
      (ELISA) was established to measure the levels of anti-Mycoplasma pneumoniae IgG
      and IgM antibodies. RESULTS: Regarding the level of anti-Mycoplasma pneumoniae
      IgM, the titer of this marker was positive in 4.1% of patients with ischemic
      stroke, while none of the subjects in control group had positive titer for this
      antibody (OR = 1.043, 95%CI: 1.001 - 1.087, p = 0.043). The rate of positivity
      for anti-Mycoplasma pneumoniae IgG in ischemic stroke patients was significantly
      higher than in the control group (28.5% versus 13.4%, p = 0.031). Odds ratio for
      exposure to M. pneumoniae was 2.24 times of the control subjects. The level of
      anti-Mycoplasma pneumoniae IgM was independent to both sex and age variables in
      patients group (p = 0.77). The level of anti-Mycoplasma pneumoniae IgG did not
      depend on subjects' gender in control group, but was significantly higher in men
      compared with women in patients group. CONCLUSION: A high level of anti
      Mycoplasma pneumoniae IgM and IgG antibodies indicate a significant association
      of M. pneumoniae infection and history of this infection with increased risk for
      ischemic stroke.

PMID- 28491250
TI  - Prevalence of Hepatitis C virus Genotype 3a in patients with Hodgkin and Non
      Hodgkin Lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) is a major public health
      problem worldwide. Replication and persistence of HCV genome have been described
      in the liver tissue as well as B cells lymphocyte. Several investigations have
      reported that long-term persistence of HCV in B cells may result in Hodgkin and
      Non-Hodgkin lymphoma. This study was aimed to determine frequency of HCV RNA in
      histological tissues obtained from patients suffered from Hodgkin and Non-Hodgkin
      lymphoma. MATERIALS AND METHODS: 52 formalin-fixed paraffin-embedded tissue
      blocks including 23 (44.3%) Hodgkin and 29 (55.7%) Non-Hodgkin samples were
      collected and five micrometer sections were prepared. RNA was extracted and cDNA
      was synthesized. Two consecutive Nested RT-PCR assays were carried out for
      detection of HCV 5' UTR and core gene. RT-PCR products were sequenced and aligned
      to construct HCV phylogenic tree to evaluate the homology of sequences in
      comparison to the reference sequences retrieved from Genbank. RESULTS: Overall, 6
      Non-Hodgkin (20.6%) and 3 Hodgkin lymphoma (13.04%) samples showed positive PCR
      results for both 5' UTR and HCV core RNA via nested PCR (P<0.469). Sequencing
      results revealed that all detected HCV RNA samples belonged to the genotype 3a.
      CONCLUSION: Despite low prevalence of HCV infection in Iran, high frequency of
      HCV RNA genotypes 3a (17.3%) has been found in patients with Hodgkin and Non
      Hodgkin lymphoma. To improve treatment regimens, screening of HCV RNA in patients
      suffered from Hodgkin or Non-Hodgkin lymphoma is recommended which can be done
      through highly sensitive molecular means before and after immunosuppression
      status.

PMID- 28491251
TI  - Significance of IgG optical density ratios (index value) in single reactive anti
      Dengue virus IgG capture ELISA.
AB  - BACKGROUND AND OBJECTIVES: A single reactive IgG anti-Dengue virus ELISA test in
      the absence of IgM antibodies or NS1 antigen may denote current infection or past
      exposure to the virus. To determine whether IgG index value can be used to
      identify true current dengue infection we conducted a prospective observational
      study. MATERIALS AND METHODS: Suspected dengue patients (n =1745) were tested in
      their first specimen by MAC-ELISA, GAC-ELISA and NS1 antigen ELISA. Patients with
      MAC-ELISA and NS1Antigen non-reactive but GAC-ELISA reactive results (n =57) in
      their first test were followed up and repeated sampling was asked for IgG index
      values were calculated according to the manufacturer's instruction and classified
      as: low (2.2-2.5), medium (2.5-4.0) and high (>4.0). RESULTS: 16 out of 57
      patients (28.1%) had low IgG Index value whereas 26 cases (45.6%) were
      categorized as medium and 15(26.3%) were classified as patients with high IgG
      index. Nine patients with paired reactive serology or antigen positive status
      were categorised as serologically confirmed dengue fever, 11 patients as not
      dengue with categorical evidence of other infections while the rest 37 casas with
      clinical, radiological and laboratory parameters suggestive of dengue but no
      serological confirmation as possible dengue. Among confirmed, possible and non
      Dengue cases, 33.3, 32.4 and 0.0% had high Index value in comparison with 22.2,
      29.7 and 27.3% showing low Index values, respectively. CONCLUSION: Our results
      suggested a high IgG response in favour of true dengue infection than past
      exposure while no conclusions should drawn from a low or medium reactive GAC
      ELISA results in the absence of IgM antibodies and NS1 Ag.

PMID- 28491252
TI  - Inhibitory effects of carvacrol on the expression of secreted aspartyl
      proteinases 1-3 in fluconazole-resistant Candida albicans isolates.
AB  - BACKGROUND AND OBJECTIVES: Secreted Aspartyl Proteinase (SAP) is one of the main
      virulence factors in the pathogenesis of Candida. This enzyme is encoded by a
      family of at least ten genes. Among these genes, the role of SAP1-3 in mucosal
      infections is evident. This study aimed to investigate the expression of SAP1-3
      genes of Candida albicans isolates after treatment with Echinophora platyloba
      extract, carvacrol and caspofungin drug. MATERIALS AND METHODS: Vaginal samples
      of 68 women with suspected vaginitis were obtained and cultured. Canida albicans
      species were identified using phenotypic and genotyping methods.
      Spectrophotometry was used to investigate the presence of SAP protein in the
      vaginal samples, and SDS-PAGE was used to confirm its protein composition. Real
      time PCR was performed to ascertain the effects of subinhibitory concentrations
      of Echinophora platyloba extract, carvacrol and caspofungin on the expression of
      SAP1-3 genes before and after treatment. RESULTS: C. albicans was found as the
      abundant species (59.6%), and different amounts of SAP were present in all
      vaginal samples, which were higher than Candida krusei strain. The protein
      composition of SAP in C. albicans samples was estimated with the approximate
      molecular weight of 45 kDa. mRNA levels of total SAP in FLU-resistant isolates
      (P=0.01) were more than those of FLU-susceptible isolates (P=0.07). The findings
      indicated that carvacrol is effective in reduction of SAP1-3 expression with a
      particular effect against FLU-resistant isolates. CONCLUSION: Carvacrol contains
      an essential oil (carvacrol); therefore, it can be considered as an alternative
      effective antifungal compound.

PMID- 28491254
TI  - Laser Science and its Applications in Prosthetic Rehabilitation.
AB  - The minimal invasive nature of lasers, with quick tissue response and healing has
      made them a very attractive technology in various fields of dentistry which
      serves as a tool to create a better result than ever before. The rapid
      development of lasers and their wavelengths with variety of applications on soft
      and hard tissues may continue to have major impact on the scope and practice in
      prosthetic dentistry. The purpose of this article is to make every clinician
      familiar with the fundamentals of lasers and different laser systems to
      incorporate into their clinical practices.

PMID- 28491253
TI  - Isolation, molecular identification, and antifungal susceptibility profiles of
      vaginal isolates of Candida species.
AB  - BACKGROUND AND OBJECTIVES: Vulvovaginal candidiasis is a common fungal infection
      among women during reproductive ages. Although, Candida albicans is accounted as
      the main etiologic agent of vaginitis, non-albicans species have arisen during
      last years. Resistant to antifungal drugs especially, fluconazole has been more
      reported by researchers from around the World. The aims of this study were to
      determine the prevalence of vulvovaginal candidiasis among suspected patients
      with vaginitis, the frequency of Candida species, and the susceptibility profiles
      of isolates to caspofungin, fluconazole and clotrimazole. MATERIALS AND METHODS:
      One hundred and twenty suspected women with vaginitis were examined by specialist
      physician and sampled using moisture swabs. Swabs were inoculated on CHROMagar
      Candida plates, incubated at 35 degrees C and detected all isolated Candida
      species using morphological, microcopy and molecular methods. The antifungal
      susceptibility tests with caspofungin, fluconazole and clotrimazole were applied
      using microdilution and Resazurin dye methods against all isolated yeasts.
      RESULTS: The cultures were positive for 34(28.3%) samples and three Candida
      species including; C. albicans (88.2%), C. glabrata (8.8%) and C. kefyr (2.9%).
      Our study shows that only one isolate of C. albicans was resistant to caspofungin
      at the concentration of 2 MUg/ml after 24h incubation that increased to 2
      isolates after 48h incubation. All isolates were sensitive to fluconazole at the
      MIC ranges of 1-0.25 MUg/ml, while 88.2% of them were inhibited at 0.25 MUg/mL of
      clotrimazole. Candida albicans remains the most common agent of fungal vaginitis.
      CONCLUSION: Although all of Candida isolates were susceptible to fluconazole in
      vitro, it should be used with caution for empirical therapy due to more resistant
      rates in clinic. In addition, due to valuable sensitivity of all tested strains
      to caspofungin, it potentially can be presented as the first line therapy for
      Candida vaginitis.

PMID- 28491255
TI  - The Effect of Femtosecond Laser Treatment on the Effectiveness of Resin-Zirconia
      Adhesive: An In Vitro Study.
AB  - Introduction: When aesthetics is compromised, dental ceramics are excellent
      materials for dental restorations; owing to their optical properties and
      biocompatibility, zirconia ceramics are particularly interesting. Self-adhesive
      resin cements are the most suitable for bonding to zirconia ceramics, but
      traditional adhesive chemistry is ineffective and surface treatments are required
      to improve the adhesive bonding between resin and zirconia. The aim of this study
      was to evaluate the effect of femtosecond laser treatment on the shear bond
      strength (SBS) of self-adhesive resin cement on zirconia surfaces and to contrast
      it with other different surface conditioning methods. Methods: Sixty square
      shaped zirconia samples were divided randomly into four groups (n = 15) according
      to their surface conditioning method: the NT group - no surface treatment; the
      APA25 group - airborne abrasion with 25 MUm alumina particles; the TSC group -
      tribochemical silica coating, and the FS group - femtosecond laser irradiation
      (800 nm, 4 mJ, 40 fs/pulse, 1 kHz). Self-adhesive resin cements were bonded at
      the centre of samples, and after 72 hours, they were tested for SBS with a
      universal testing machine at a crosshead speed of 0.5 mm/min, until fracture.
      Five zirconia surfaces for each group were subjected to a surface morphology
      analysis by scanning electron microscopy (SEM). The failure modes were noted and
      a third of the specimens were prepared to morphological analysis. Results: The NT
      group showed lower SBS values than the other groups. Femtosecond laser treatment
      demonstrated higher values than the control and APA25 groups and similar values
      to those of the TSC group. In the APA25 group, the surface conditioning method
      had values close to those of the TSC group, but lower than those obtained with
      femtosecond laser treatment. Conclusion: The treatment of zirconia with
      femtosecond laser irradiation created a consistent and profound surface
      roughness, improving the adhesive effectiveness of the zirconia-resin interface.

PMID- 28491256
TI  - Effect of Antimicrobial Photodynamic Therapy as an Adjunct to Nonsurgical
      Treatment of Deep Periodontal Pockets: A Clinical Study.
AB  - Introduction: Deep periodontal pockets pose a great challenge for nonsurgical
      periodontal treatment. Scaling and root planing (SRP) alone may not suffice in
      cases where surgical therapy cannot be undertaken. Various recent studies have
      suggested the use of antimicrobial Photodynamic Therapy (aPDT) for the management
      of periodontal infections. The aim of this study was to evaluate the effects of
      using aPDT along with SRP, compared to SRP alone for the management of deep
      periodontal pockets. Methods: Thirty patients with chronic periodontitis, who met
      the criteria of having periodontal pockets with depth >= 6 mm and bleeding on
      probing (BOP) in at least 2 different quadrants were included. After SRP, one
      quadrant was randomly selected for aPDT (test), while another served as control.
      Clinical parameters i.e. plaque index (PI), modified sulcular bleeding index
      (mSBI), probing depth (PD) and clinical attachment level (CAL) were measured at
      baseline, 1 month and 3 months post-treatment intervals. Results: All clinical
      parameters significantly improved in both groups after 1 and 3 months. At 1-month
      interval, inter-group difference in mean change was statistically significant (P
      < 0.05) in terms of mSBI (0.85 +/- 0.41in test vs 0.54 +/- 0.47 in control group)
      and PD (1.77+/-0.86 in test vs 1.3 +/- 0.95 in control group). At 3 months
      interval, no statistically significant difference was observed between test and
      control groups except in terms of mSBI (0.97 +/- 0.45 in test vs 0.73 +/- 0.42 in
      control group). Conclusion: aPDT appears to play an additional role in reduction
      of gingival inflammation when used along with nonsurgical mechanical debridement
      of deep periodontal pockets.

PMID- 28491257
TI  - A Split Mouth Randomized Clinical Comparative Study to Evaluate the Efficacy of
      Gingival Depigmentation Procedure Using Conventional Scalpel Technique or Diode
      Laser.
AB  - Introduction: Dark or black coloured gingiva is an esthetic concern especially in
      subjects with high lip line or gummy smile. Gingival depigmentation procedure is
      a type of perioplastic surgery where the gingival epithelium is excised with
      various techniques to lighten the colour of the gingiva. The aim of this study
      was to compare the clinical efficacy of gingival depigmentation procedure with
      conventional scalpel technique and diode laser application. Methods: This split
      mouth randomized study was conducted on 12 subjects (18-40 years of age),
      exhibiting melanin hyperpigmentation of gingiva. The anterior labial sextant of
      maxilla and mandible were divided into two halves involving three anterior teeth
      i.e. central incisor, lateral incisor and canine on each side. The divided areas
      were randomly allotted for depigmentation procedure either with scalpel technique
      or diode laser operating at 980 nm wavelength. Various parameters such as
      bleeding, pain, difficulty of procedure and wound healing were assessed and
      compared between the two techniques. The level of melanin pigment was assessed
      with Dummette Gupta index and photographic analysis with the help of adobe
      software. The subjects were followed up to one year to see for recurrence of
      melanin pigmentation. Results: Bleeding during surgery, pain score and difficulty
      of procedure assessed by the operator were statistically higher for scalpel
      technique as compared to laser technique. Wound healing did not show any
      statistical significant difference between both techniques. Gingival
      depigmentation procedures with scalpel as well as laser technique were effective
      when compared preoperatively and at consecutive postoperative visits, and this
      was statistically significant. Comparison of melanin depigmentation procedure
      between scalpel and laser technique did not show any significant differences at
      all postoperative intervals. Conclusion: The findings of the present study
      suggest that gingival depigmentation was effective with both scalpel and laser
      techniques. However, the laser treated sites showed reduced pain experienced by
      the patient and better operator comfort. Slight melanin repigmentation was
      observed in three subjects treated with scalpel depigmentation procedure at the
      end of one year.

PMID- 28491258
TI  - The Effect of Probe Pressure on In Vivo Single Fiber Reflectance Spectroscopy.
AB  - Introduction: Single fiber reflectance spectroscopy (SFRS) is a noninvasive
      procedure to quantitate tissue absorption and scattering properties. It can be
      used to diagnose different diseases such as malignancy and pre-cancerous
      conditions. The measurement is done with a fiber optic probe in contact with the
      tissue surface. Herein, the effect of probe pressure on the extracted parameters
      from human lip spectra was studied. Methods: Thirty-three normal subjects were
      examined with three exerted pressure levels on the right, middle and left parts
      of their lips. Results: The results showed variation of spectroscopic parameters
      with different pressure levels. However, the effect was seen between a very mild
      contact (pressure 1) and the other reasonably practical pressure levels normally
      used in the medical centers. Conclusion: SFRS can be used as a reliable
      diagnostic tool in clinics.

PMID- 28491259
TI  - The Antibacterial Effect of Additional Photodynamic Therapy in Failed
      Endodontically Treated Teeth: A Pilot Study.
AB  - Introduction: Root canal therapy as a routine dental procedure has resulted in
      retention of millions of teeth that would otherwise be lost. Unfortunately,
      successful outcomes are not always achievable within initial endodontic
      treatments, and that necessitates further treatment. Nonsurgical retreatment is
      the first choice in most clinical situations. The aim of this clinical pilot
      study was to assess the effect of additional photodynamic therapy (PDT) on
      intraradicular bacterial load following retreatment of failed previously root
      treated teeth. Methods: Thirty single-rooted/canalled endodontically treated
      matured teeth (in 27 healthy patients) accompanied by apical periodontitis (AP)
      were selected for this study. Standard protocol was followed for nonsurgical
      retreatment of each tooth. Microbiological samples were taken after establishment
      of apical patency, finished cleaning/shaping procedure, and PDT (665 nm, 1 W, 240
      seconds). All samples were cultured for 72 hours and colony-forming unit (CFU)
      was counted. McNemar test was used for statistical analysis of the data. The
      level of significance was set at 0.001. Results: Routine cleaning and shaping
      resulted in twenty four negative (80%) out of 30 cultures. Four additional
      negative results were obtained after additional PDT (93.3%). The addition of PDT
      to routine procedures significantly enhanced the number of bacteria-free samples
      (P < 0.001). Conclusion: Regarding elimination of intraradicular microbiota,
      additional PDT may increase the effectiveness of conventional chemomechanical
      preparation in previously root filled teeth accompanied by AP. Well controlled
      randomized clinical trials should be planned for future.

PMID- 28491260
TI  - Evaluation of the Effects of Er,Cr:YSGG Laser, Ultrasonic Scaler and Curette on
      Root Surface Profile Using Surface Analyser and Scanning Electron Microscope: An
      In Vitro Study.
AB  - Introduction: The periodontal therapy is primarily targeted at removal of dental
      plaque and plaque retentive factors. Although the thorough removal of adherent
      plaque, calculus and infected root cementum is desirable, it is not always
      achieved by conventional modalities. To accomplish more efficient results several
      alternative devices have been used. Lasers are one of the most promising
      modalities for nonsurgical periodontal treatment as they can achieve excellent
      tissue ablation with strong bactericidal and detoxification effects. Methods:
      Thirty freshly extracted premolars were selected and decoronated. The mesial
      surface of each root was divided vertically into four approximately equal parts.
      These were distributed into four group based on the root surface treatment. Part
      A (n = 30) was taken as control and no instrumentation was performed. Part B (n =
      30) was irradiated by Erbium, Chromium doped Yttrium Scandium Gallium Garnet
      (Er,Cr:YSGG) laser. Part C (n = 30) was treated by piezoelectric ultrasonic
      scaler. Part D (n = 30) was treated by Gracey curette. The surface roughness was
      quantitatively analyzed by profilometer using roughness average (Ra) value, while
      presence of smear layer, cracks, craters and melting of surface were analyzed
      using scanning electron microscope (SEM). The means across the groups were
      statistically compared with control using Dunnett test. Results: Among the test
      groups, Er,Cr:YSGG laser group showed maximum surface roughness (mean Ra value of
      4.14 MUm) as compared to ultrasonic scaler (1.727 MUm) and curette group (1.22
      MUm). However, surface with smear layer were found to be maximum (50%) in curette
      treated samples and minimum (20%) in laser treated ones. Maximum cracks (83.34%)
      were produced by ultrasonic scaler, and minimum (43.33%) by curettes. Crater
      formation was maximum (50%) in laser treated samples and minimum (3.33%) in
      curette treated ones. 63.33% samples treated by laser demonstrated melting of
      root surface, followed by ultrasonic scaler and curettes. Conclusion: Er,Cr:YSGG
      laser produced maximum microstructural changes on root surface that can influence
      the attachment of soft periodontal tissues as well as plaque and calculus
      deposition. In vivo studies are needed to validate these results and to evaluate
      their clinical effects.

PMID- 28491261
TI  - Effect of Combined Therapy Using Diode Laser and Photodynamic Therapy on Levels
      of IL-17 in Gingival Crevicular Fluid in Patients With Chronic Periodontitis.
AB  - Introduction: The aim of this study was to evaluate the efficacy of combination
      therapy of diode laser and photodynamic therapy (PDT) as an adjunct to scaling
      and root planing (SRP) on interleukin-17 (IL-17) levels in gingival crevicular
      fluid (GCF) in patients with chronic periodontitis. Methods: Thirty subjects with
      chronic periodontitis were included. All teeth received periodontal treatment
      comprising of SRP. Using a split mouth study design, the test group was
      additionally treated with a combination therapy of diode laser and PDT. GCF was
      collected to evaluate IL-17 levels at baseline and 3 months. Results: There was
      no difference in baseline values for levels of IL-17 in GCF in the test group and
      the control group. A significant decrease in GCF levels of IL-17 was observed in
      both treatment groups 3 months after treatment (P < 0.001). However, the
      treatment groups showed no significant difference (P > 0.05). Conclusion: Based
      on the results of the present study it was concluded that, GCF levels of IL-17
      changed significantly after treatment regardless of treatment modality.

PMID- 28491262
TI  - White Fibrous Papulosis of the Neck Treated With Fractionated 1550-nm Erbium
      Glass Laser: A Case Report.
AB  - Introduction: Despite its clinical features of multiple, confluent, small,
      whitish, smooth, and clear-demarcate papules on the neck and back, the
      pathogenesis of white fibrous papulosis of the neck (WFPN) is still unknown. The
      lesions increase progressively and do not regress over time. However, no
      effective treatment has yet been identified. Case Report: We reported the
      successful results of a female patient receiving efficacious treatment for her
      extensive lesions of WFPN with nonablative fractional photothermolysis laser
      (Fractionated 1550-Erbium Glass laser). Conclusion: This photothermolysis laser
      could then be suggestive as the therapeutic option for WFPN.

PMID- 28491263
TI  - Periosteal Releasing Incision With Diode Laser in Guided Bone Regeneration
      Procedure: A Case Series.
AB  - Introduction: Periosteal releasing incision (PRI) is nearly always essential to
      advance the flap sufficiently for a tension-free flap closure in bone
      augmentation procedures. However, hematoma, swelling, and pain are recognized as
      the main consequences of PRI with scalpel. The aim of this case series was to
      investigate the effectiveness of laser-assisted PRI in guided bone regeneration
      (GBR) procedure. In addition, postoperative hematoma, swelling, and pain and
      implant success were assessed. Methods: Seventeen patients needed GBR were
      included in this study. Diode laser (940 nm, 2 W, pulse interval: 1 ms, pulse
      length: 1 ms, contact mode, 400-MUm fiber tip) was used in a contact mode to cut
      the periosteum to create a tension-free flap. Facial hematoma, swelling, pain,
      and the number of consumed nonsteroidal anti-inflammatory drugs (NSAIDs) were
      measured for the six postoperative days. Six months after implant loading,
      implant success was evaluated. Results: Minimal bleeding was encountered during
      the procedure. A tension-free primary closure of the flap was achieved in all
      cases. The clinical healing of the surgical area was uneventful. None of the
      patients experienced hematoma, ecchymosis, or intense swelling after surgery. The
      mean value of maximum pain (visual analogue scale - VAS) was 20.59 +/- 12.10 mm
      (mild pain). Patients did not need to use NSAID after four postoperative days.
      All implants were successful and functional and none of them failed after 6
      months of implant loading. Conclusion: This study revealed the effectiveness of
      laser-assisted PRI in GBR procedure. This technique was accompanied with minimal
      sequelae at the first postoperative week. All implants were successful and no
      complication was noted during the course of this study.

PMID- 28491264
TI  - Priming radioimmunotherapy with external beam radiation in patients with relapsed
      low grade non-Hodgkin lymphoma.
AB  - BACKGROUND: The aim of this study was to evaluate the outcomes of priming salvage
      radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in
      patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). METHODS: Patients
      who received salvage RIT with or without 2 * 2 Gy EBRT between March 2009 and
      February 2013 were retrospectively reviewed at a single institution. Planning
      target volume (PTV) for EBRT was created by adding a 1-2 cm expansion to the
      gross tumor volume depending on the anatomical location. Kaplan-Meier method via
      log-rank was employed to analyze the endpoints freedom from progression (FFP) and
      overall survival (OS). RESULTS: We identified 22 patients who received salvage
      RIT without chemotherapy with a median follow up of 34 months. Of these, 9 (41%)
      patients were treated with EBRT immediately prior to RIT, and 13 (59%) received
      salvage RIT alone. Median FFP was not reached in patients who underwent
      combination treatment, while it was 9 months for patients treated with RIT alone
      (p = 0.02). OS for all patients at 36 months was 80.3% with no significant
      difference between the two groups (p = 0.88). On univariate analysis, the
      addition of EBRT was associated with improved FFP [hazard ratio (HR) = 4.17; 95%
      confidence interval (CI), 1.24-19.1; p = 0.02)]. No long term toxicities were
      reported in both groups. CONCLUSIONS: RIT outcomes and effects were improved with
      addition of low-dose EBRT immediately prior to it, in the treatment of relapsed
      LG-NHL with no additional toxicity. This study is hypothesis-generating and the
      findings should be validated in prospective studies.

PMID- 28491265
TI  - Experience with ruxolitinib in the treatment of polycythaemia vera.
AB  - Polycythaemia vera (PV) is a myeloproliferative neoplasm classically
      characterized by an erythrocytosis and is associated with a high risk of
      thromboembolic events, constitutional symptoms burden and risk of transformation
      to myelofibrosis and acute myeloid leukaemia. Therapy is directed at the
      haematocrit (HCT) to reduce the risk of thrombotic events and usually comprises
      low-dose aspirin and phlebotomy to maintain HCT at >45%. Frequently in addition,
      cytoreductive therapy is indicated in high-risk patients for normalizing
      haematological parameters to mitigate the occurrence of thromboembolic events.
      Unfortunately, there is no clear evidence that current therapies reduce the risk
      of transformation to myelofibrosis and for some a risk of a therapy related
      complication is unknown for example leukaemia due to hydroxycarbamide (HC). First
      line therapy for treating PV remains HC or interferon, the latter most often in
      younger patients, especially those of childbearing age. However, therapy related
      intolerance or resistance is a common feature and results in limited treatment
      options for such patients. The discovery of the JAK2 V617F mutation and
      consequently targeted therapy with Janus kinase inhibitors, in particular
      ruxolitinib, has extended the spectrum of agents that can be used as second or
      third line in PV. The findings of the phase II trial RESPONSE and the preliminary
      data from RESPONSE 2 trial have identified a role for ruxolitinib in PV patients
      who are resistant or intolerant to HC. In this article, using clinical cases we
      demonstrate our experience with ruxolitinib highlighting the clinical benefits
      and limitations we encountered in clinical practice.

PMID- 28491266
TI  - Point-of-care ultrasonography (POCUS) in hemophilia A: a commentary on current
      status and its potential role for improving prophylaxis management in severe
      hemophilia A.
AB  - In patients with severe hemophilia A, recurrent bleeding into joints results in
      increased morbidity and reduced quality of life. Prophylaxis using replacement
      factor products, especially when initiated early, has established benefits in
      terms of reducing joint bleeds and preserving joint function. Poor adherence to
      prophylactic regimens is a common cause for breakthrough bleeds and resultant
      arthropathy. Improving prophylaxis management, especially in the transitional age
      group, is a challenge. Here, we discuss the current status of ultrasonography
      (US) in hemophilia A, challenges in its wider implementation, and the potential
      for use of point-of-care US (POCUS) as an adjunct in the routine management of
      patients with hemophilia following prophylaxis regimens. Using POCUS, in which US
      is performed by trained hematologists and nonphysician operators (rather than
      comprehensive US performed by imaging specialists), specific clinical questions
      can be addressed in a time-efficient, user-friendly manner to promote adherence
      to prophylaxis and guide or modify treatment approaches. This review also
      discusses barriers to acceptance of POCUS as a part of routine management of
      patients with hemophilia, including questions related to its diagnostic accuracy,
      dependence on trained operators, agreement on appropriate scoring systems, and
      potential usefulness in patient management.

PMID- 28491267
TI  - Update on the management of giant cell arteritis.
AB  - Giant cell arteritis (GCA) is a large vessel vasculitis that may be associated
      with significant complications such as blindness, stroke, or aortic aneurysm and
      dissection in a subset of patients. Given the serious side effects associated
      with prolonged courses of glucocorticoids and frequent relapses experienced when
      doses are tapered, increased efforts are being dedicated to the discovery of
      safer and more effective therapies to control this disease. The purpose of this
      review is to critically evaluate the role of glucocorticoid-sparing agents in the
      medical management of GCA with a special focus on the most recent evidence
      regarding the role of biologic agents, including tocilizumab (TCZ), abatacept and
      ustekinumab, and other novel therapies.

PMID- 28491268
TI  - Umeclidinium in chronic obstructive pulmonary disease: latest evidence and place
      in therapy.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity,
      mortality and health care expenditure throughout the world. COPD guidelines
      recommend the use of long-acting muscarinic antagonist (LAMA) either alone or in
      combination with a long-acting beta2 agonist (LABA). For over 10 years,
      tiotropium was the only LAMA that was used in the management of COPD. Over the
      past few years, various new drugs have been identified that act on the muscarinic
      receptors and beta2 receptors. Umeclidinium (Umec) is a new LAMA currently
      approved for use in patients with COPD either as monotherapy or in combination
      with vilanterol (Vil). Both Umec alone and in combination with Vil delivered
      through a multi-dose dry powder ElliptaTM device have shown improvement in lung
      function, health-related quality of life and exacerbation frequency in patients
      with COPD. This review provides an overview of the pharmacology, pharmacodynamics
      and pharmacokinetics of Umec, and evaluates the clinical efficacy and safety
      studies in patients with COPD.

PMID- 28491269
TI  - Curve Appeal: Exploring Individual Differences in Preference for Curved Versus
      Angular Objects.
AB  - A preference for smooth curvature, as opposed to angularity, is a well
      established finding for lines, two-dimensional shapes, and complex objects, but
      little is known about individual differences. We used two-dimensional black-and
      white shapes-randomly generated irregular polygons, and arrays of circles and
      hexagons-and measured many individual differences, including artistic expertise,
      personality, and cognitive style. As expected, people preferred curved over
      angular stimuli, and people's degree of curvature preference correlated across
      the two sets of shapes. Multilevel models showed varying patterns of interaction
      between shape and individual differences. For the irregular polygons, people
      higher in artistic expertise or openness to experience showed a greater
      preference for curvature. This pattern was not evident for the arrays of circles
      and hexagons. We discuss the results in relation to the nature of the stimuli,
      and we conclude that individual differences do play a role in moderating the
      preference for smooth curvature.

PMID- 28491270
TI  - Ways of Viewing Pictorial Plasticity.
AB  - The plastic effect is historically used to denote various forms of stereopsis.
      The vivid impression of depth often associated with binocular stereopsis can also
      be achieved in other ways, for example, using a synopter. Accounts of this go
      back over a hundred years. These ways of viewing all aim to diminish sensorial
      evidence that the picture is physically flat. Although various viewing modes have
      been proposed in the literature, their effects have never been compared. In the
      current study, we compared three viewing modes: monocular blur, synoptic viewing,
      and free viewing (using a placebo synopter). By designing a physical embodiment
      that was indistinguishable for the three experimental conditions, we kept
      observers naive with respect to the differences between them; 197 observers
      participated in an experiment where the three viewing modes were compared by
      performing a rating task. Results indicate that synoptic viewing causes the
      largest plastic effect. Monocular blur scores lower than synoptic viewing but is
      still rated significantly higher than the baseline conditions. The results
      strengthen the idea that synoptic viewing is not due to a placebo effect.
      Furthermore, monocular blur has been verified for the first time as a way of
      experiencing the plastic effect, although the effect is smaller than synoptic
      viewing. We discuss the results with respect to the theoretical basis for the
      plastic effect. We show that current theories are not described with sufficient
      details to explain the differences we found.

PMID- 28491271
TI  - Stereoscopic Segmentation Cues Improve Visual Timing Performance in
      Spatiotemporally Cluttered Environments.
AB  - Recently, Cass and Van der Burg demonstrated that temporal order judgment (TOJ)
      precision could be profoundly impaired by the mere presence of dynamic visual
      clutter elsewhere in the visual field. This study examines whether presenting
      target and distractor objects in different depth planes might ameliorate this
      remote temporal camouflage (RTC) effect. TOJ thresholds were measured under
      static and dynamic (flickering) distractor conditions. In Experiment 1, targets
      were presented at zero, crossed, or uncrossed disparity, with distractors fixed
      at zero disparity. Thresholds were significantly elevated under dynamic compared
      with static contextual conditions, replicating the RTC effect. Crossed but not
      uncrossed disparity targets improved performance in dynamic distractor contexts,
      which otherwise produce substantial RTC. In Experiment 2, the assignment of
      disparity was reversed: targets fixed at zero disparity; distractors crossed,
      uncrossed, or zero. Under these conditions, thresholds improved significantly in
      the nonzero distractor disparity conditions. These results indicate that
      presenting target and distractor objects in different planes can significantly
      improve TOJ performance in dynamic conditions. In Experiment 3, targets were each
      presented with a different sign of disparity (e.g., one crossed and the other
      uncrossed), with no resulting performance benefits. Results suggest that
      disparity can be used to alleviate the performance-diminishing effects of RTC,
      but only if both targets constitute a single and unique disparity-defined
      surface.

PMID- 28491272
TI  - Sensitivity to Nonaccidental Configurations of Two-Line Stimuli.
AB  - According to Recognition-By-Components theory, object recognition relies on a
      specific subset of three-dimensional shapes called geons. In particular, these
      configurations constitute a powerful cue to three-dimensional object
      reconstruction because their two-dimensional projection remains viewpoint
      invariant. While a large body of literature has demonstrated sensitivity to
      changes in these so-called nonaccidental configurations, it remains unclear what
      information is used in establishing such sensitivity. In this study, we explored
      the possibility that nonaccidental configurations can already be inferred from
      the basic constituents of objects, namely, their edges. We constructed a set of
      stimuli composed of two lines corresponding to various nonaccidental properties
      and configurations underlying the distinction between geons, including
      collinearity, alignment, curvature of contours, curvature of configuration axis,
      expansion, cotermination, and junction type. Using a simple visual search
      paradigm, we demonstrated that participants were faster at detecting targets that
      differed from distractors in a nonaccidental property than in a metric property.
      We also found that only some but not all of the observed sensitivity could have
      resulted from simple low-level properties of our stimuli. Given that such
      sensitivity emerged from a configuration of only two lines, our results support
      the view that nonaccidental configurations could be encoded throughout the visual
      processing hierarchy even in the absence of object context.

PMID- 28491273
TI  - Estimating the Illumination Direction From Three-Dimensional Texture of Brownian
      Surfaces.
AB  - We studied whether human observers can estimate the illumination direction from
      3D textures of random Brownian surfaces, containing undulations over a range of
      scales. The locally Lambertian surfaces were illuminated with a collimated beam
      from random directions. The surfaces had a uniform albedo and thus texture
      appeared only through shading and shadowing. The data confirm earlier results
      with Gaussian surfaces, containing undulations of a single scale. Observers were
      able to accurately estimate the source azimuth. If shading dominated the images,
      the observers committed 180 degrees  errors. If cast shadows were present, they
      resolved this convex-concave-ambiguity almost completely. Thus, observers relied
      on second-order statistics in the shading regime and used an unidentified first
      order cue in the shadow regime. The source elevations could also be estimated,
      which can be explained by the observers' exploitation of the statistical
      homogeneity of the stimulus set. The fraction of the surface that is in shadow
      and the median intensity are likely cues for these elevation estimates.

PMID- 28491275
TI  - Outflow tract septation and the aortic arch system in reptiles: lessons for
      understanding the mammalian heart.
AB  - BACKGROUND: Cardiac outflow tract patterning and cell contribution are studied
      using an evo-devo approach to reveal insight into the development of aorto
      pulmonary septation. RESULTS: We studied embryonic stages of reptile hearts
      (lizard, turtle and crocodile) and compared these to avian and mammalian
      development. Immunohistochemistry allowed us to indicate where the essential cell
      components in the outflow tract and aortic sac were deployed, more specifically
      endocardial, neural crest and second heart field cells. The neural crest-derived
      aorto-pulmonary septum separates the pulmonary trunk from both aortae in
      reptiles, presenting with a left visceral and a right systemic aorta arising from
      the unseptated ventricle. Second heart field-derived cells function as flow
      dividers between both aortae and between the two pulmonary arteries. In birds,
      the left visceral aorta disappears early in development, while the right systemic
      aorta persists. This leads to a fusion of the aorto-pulmonary septum and the
      aortic flow divider (second heart field population) forming an avian aorto
      pulmonary septal complex. In mammals, there is also a second heart field-derived
      aortic flow divider, albeit at a more distal site, while the aorto-pulmonary
      septum separates the aortic trunk from the pulmonary trunk. As in birds there is
      fusion with second heart field-derived cells albeit from the pulmonary flow
      divider as the right 6th pharyngeal arch artery disappears, resulting in a
      mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the
      main septal and parietal endocardial cushions receive neural crest cells that are
      functional in fusion and myocardialization of the outflow tract septum. Longer
      lasting septation in crocodiles demonstrates a heterochrony in development. In
      other reptiles with no indication of incursion of neural crest cells, there is
      either no myocardialized outflow tract septum (lizard) or it is vestigial
      (turtle). Crocodiles are unique in bearing a central shunt, the foramen of
      Panizza, between the roots of both aortae. Finally, the soft-shell turtle
      investigated here exhibits a spongy histology of the developing carotid arteries
      supposedly related to regulation of blood flow during pharyngeal excretion in
      this species. CONCLUSIONS: This is the first time that is shown that an interplay
      of second heart field-derived flow dividers with a neural crest-derived cell
      population is a variable but common, denominator across all species studied for
      vascular patterning and outflow tract septation. The observed differences in
      normal development of reptiles may have impact on the understanding of
      development of human congenital outflow tract malformations.

PMID- 28491274
TI  - Biomimetic strategies for fracture repair: Engineering the cell microenvironment
      for directed tissue formation.
AB  - Complications resulting from impaired fracture healing have major clinical
      implications on fracture management strategies. Novel concepts taken from
      developmental biology have driven research strategies towards the elaboration of
      regenerative approaches that can truly harness the complex cellular events
      involved in tissue formation and repair. Advances in polymer technology and a
      better understanding of naturally derived scaffolds have given rise to novel
      biomaterials with an increasing ability to recapitulate native tissue
      environments. This coupled with advances in the understanding of stem cell
      biology and technology has opened new avenues for regenerative strategies with
      true clinical translatability. These advances have provided the impetus to
      develop alternative approaches to enhance the fracture repair process. We provide
      an update on these advances, with a focus on the development of novel biomimetic
      approaches for bone regeneration and their translational potential.

PMID- 28491276
TI  - Antiangiogenic effects in patients with progressive desmoplastic small round cell
      tumor: data from the French national registry dedicated to the use of off-labeled
      targeted therapy in sarcoma (OUTC's).
AB  - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a very rare
      mesenchymal tumor that mainly affects teenagers and young adults with a mean age
      at diagnosis around 20-25 years. Although initial management still needs
      standardization, many centers will use multimodal treatment including intensive
      chemotherapy, extensive surgical resection followed by radiotherapy. Despite
      this, prognosis remains very poor and the median overall survival is 25 months.
      Recurrent disease is mainly treated by chemotherapy. Recently, due to the unmet
      medical need for recurrent disease, targeted therapies were explored for DSRCT.
      METHODS: In this study, we assessed the response rate and progression free
      survival in nine cases of progressive DSRCT included in the OUTC's registry and
      treated with antiangiogenics targeted agents (sunitinib, sorafenib and
      bevacizumab). OUTC's, a French national registry, collects data about the use of
      off-label targeted therapy in sarcoma. RESULTS: Eight males and one woman were
      included, with median age at diagnosis of 27.3 years (range from 9 to 48 years).
      They received a mean 3 lines (2-5) of treatment before antiangiogenic agent
      initiation. Six patients received sunitinib, two received sorafenib and one
      bevacizumab. Median progression free survival was 3.1 months (range 2-5.5 months)
      and best response observed was 5.5 months stable disease. Most patients had
      manageable low-grade toxicities, mainly fatigue, abdominal pain and skin
      toxicity. CONCLUSIONS: Despite very limited activity of antiangiogenics in our
      study, prospective collection of cases of these rare tumors together with
      molecular data should guide therapeutic decision and enhance outcome.

PMID- 28491277
TI  - Meta-analysis of crowdsourced data compendia suggests pan-disease transcriptional
      signatures of autoimmunity.
AB  - Background: The proliferation of publicly accessible large-scale biological data
      together with increasing availability of bioinformatics tools have the potential
      to transform biomedical research. Here we report a crowdsourcing Jamboree that
      explored whether a team of volunteer biologists without formal bioinformatics
      training could use OMiCC, a crowdsourcing web platform that facilitates the reuse
      and (meta-) analysis of public gene expression data, to compile and annotate gene
      expression data, and design comparisons between disease and control sample
      groups. Methods: The Jamboree focused on several common human autoimmune
      diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS),
      type I diabetes (DM1), and rheumatoid arthritis (RA), and the corresponding mouse
      models. Meta-analyses were performed in OMiCC using comparisons constructed by
      the participants to identify 1) gene expression signatures for each disease
      (disease versus healthy controls at the gene expression and biological pathway
      levels), 2) conserved signatures across all diseases within each species (pan
      disease signatures), and 3) conserved signatures between species for each disease
      and across all diseases (cross-species signatures). Results: A large number of
      differentially expressed genes were identified for each disease based on meta
      analysis, with observed overlap among diseases both within and across species.
      Gene set/pathway enrichment of upregulated genes suggested conserved signatures
      (e.g., interferon) across all human and mouse conditions. Conclusions: Our
      Jamboree exercise provides evidence that when enabled by appropriate tools, a
      "crowd" of biologists can work together to accelerate the pace by which the
      increasingly large amounts of public data can be reused and meta-analyzed for
      generating and testing hypotheses. Our encouraging experience suggests that a
      similar crowdsourcing approach can be used to explore other biological questions.

PMID- 28491278
TI  - Recent advances in the management of acute ischemic stroke.
AB  - In recent years, several landmark trials have transformed acute ischemic stroke
      care. The most dramatic results from the field of acute endovascular intervention
      demonstrate unequivocal benefit for a select group of patients with moderate to
      severe deficits presenting within 7 hours from onset and with occlusions of
      proximal arteries in the anterior circulation. In addition, technological
      advances and workflow efficiencies have facilitated more rapid delivery of acute
      stroke interventions. This review provides an overview of recent advances in the
      management of acute ischemic stroke.

PMID- 28491279
TI  - "Mesenchymal stem cells": fact or fiction, and implications in their therapeutic
      use.
AB  - The concept of a post-natal "mesenchymal stem cell" ("MSC") originated from
      studies focused on bone marrow stromal cells (BMSCs), which are non-hematopoietic
      adherent cells, a subset of which are skeletal stem cells (SSCs), able to form
      cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes based on
      rigorous clonal and differentiation assays. Subsequently, it was speculated that
      BMSCs could form other mesodermal derivatives and even cell types from other germ
      layers. Based on BMSC surface markers, representative of fibroblastic cells, and
      imprecise differentiation assays, it was further imagined that "MSCs" are
      ubiquitous and equipotent. However, "MSCs" do not have a common embryonic origin
      and are not a lineage, but recent studies indicate that they are tissue-specific
      stem/progenitor cells. These cells share cell surface features owing to their
      fibroblastic nature, but they are not identical. They display different
      differentiation capacities based on their tissue origin but do not "trans
      differentiate" outside of their lineage, based on rigorous assays. For these
      reasons, the "MSC" term should be abandoned. Tissue-specific stem/progenitor
      cells provide the opportunity to devise methods for tissue regeneration by the
      cells themselves (tissue engineering). Their use in other forms of regenerative
      medicine based on paracrine, immunosuppressive, and immunomodulatory effects is
      far less clear.

PMID- 28491280
TI  - AR2, a novel automatic artifact reduction software method for ictal EEG
      interpretation: Validation and comparison of performance with commercially
      available software.
AB  - Objective: To develop a novel software method (AR2) for reducing muscle
      contamination of ictal scalp electroencephalogram (EEG), and validate this method
      on the basis of its performance in comparison to a commercially available
      software method (AR1) to accurately depict seizure-onset location. Methods: A
      blinded investigation used 23 EEG recordings of seizures from 8 patients. Each
      recording was uninterpretable with digital filtering because of muscle artifact
      and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers
      assessed seizure-onset time, lateralization, and region, and specified confidence
      for each determination. The two methods were validated on the basis of the number
      of readers able to render assignments, confidence, the intra-class correlation
      (ICC), and agreement with other clinical findings. Results: Among the 23
      seizures, two-thirds of the readers were able to delineate seizure-onset time in
      10 of 23 using AR1, and 15 of 23 using AR2 (p<0.01). Fewer readers could
      lateralize seizure-onset (p<0.05). The confidence measures of the assignments
      were low (probable-unlikely), but increased using AR2 (p<0.05). The ICC for
      identifying the time of seizure-onset was 0.15 (95% confidence interval (CI),
      0.11-0.18) using AR1 and 0.26 (95% CI 0.21-0.30) using AR2.  The EEG
      interpretations were often consistent with behavioral, neurophysiological, and
      neuro-radiological findings, with left sided assignments correct in 95.9% (CI
      85.7-98.9%, n=4) of cases using AR2. Conclusions: EEG artifact reduction methods
      for localizing seizure-onset does not result in high rates of interpretability,
      reader confidence, and inter-reader agreement. However, the assignments by groups
      of readers are often congruent with other clinical data. Utilization of the AR2
      software method may improve the validity of ictal EEG artifact reduction.

PMID- 28491281
TI  - Annotated mitochondrial genome with Nanopore R9 signal for Nippostrongylus
      brasiliensis.
AB  - Nippostrongylus brasiliensis, a nematode parasite of rodents, has a parasitic
      life cycle that is an extremely useful model for the study of human hookworm
      infection, particularly in regards to the induced immune response. The current
      reference genome for this parasite is highly fragmented with minimal annotation,
      but new advances in long-read sequencing suggest that a more complete and
      annotated assembly should be an achievable goal. We de-novo assembled a single
      contig mitochondrial genome from N. brasiliensis using MinION R9 nanopore data.
      The assembly was error-corrected using existing Illumina HiSeq reads, and
      annotated in full (i.e. gene boundary definitions without substantial gaps) by
      comparing with annotated genomes from similar parasite relatives. The
      mitochondrial genome has also been annotated with a preliminary electrical
      consensus sequence, using raw signal data generated from a Nanopore R9 flow cell.

PMID- 28491282
TI  - Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv antibody
      on prostate cancer, but not glioblastoma, cells.
AB  - Background: Single chain antibody (scFv) has shown interesting results in cancer
      immunotargeting approaches, due to its advantages over monoclonal antibodies.
      Regeneration and tolerance factor (RTF) is one of the most important regulators
      of extracellular and intracellular pH in eukaryotic cells. In this study, the
      inhibitory effects of a specific anti-RTF scFv were investigated and compared
      between three types of prostate cancer and two types of glioblastoma cells. 
      Methods: A phage antibody display library of scFv was used to select specific
      scFvs against RTF using panning process. The reactivity of a selected scFv was
      assessed by phage ELISA. The anti-proliferative and apoptotic effects of the
      antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG
      and A-172) cell lines were investigated by MTT and Annexin V/PI assays.  Results:
      A specific scFv with frequency 35% was selected against RTF epitope. This
      significantly inhibited the proliferation of the prostate cells after 24 h. The
      percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC
      3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The
      antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and
      LNCaP cells, respectively. No growth inhibition and apoptotic induction was
      detected for U-87 and A172 glioblastoma cells.  Conclusions: Anti-RTFscFv
      significantly reduced the proliferation of the prostate cancer cells. The
      inhibition of cell growth and apoptotic induction effects in PC-3 cells were
      greater than Du-145 and LNCaP cells. This might be due to higher expression of
      RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody.
      The resistance of glioblastoma cells to anti-RTF scFv offers the existence of
      mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The
      results suggest that the selected anti-RTF scFv antibody could be an effective
      new alternative for prostate cancer immunotherapy.

PMID- 28491283
TI  - Open Online Courses in Public Health: experience from Peoples-uni.
AB  - Open Online Courses (OOCs) are offered by Peoples-uni at http://ooc.peoples
      uni.org to complement the courses run on a separate site for academic credit at
      http://courses.peoples-uni.org. They provide a wide range of online learning
      resources beyond those usually found in credit bearing Public Health courses.
      They are self-paced, and students can enrol themselves at any time and utilise
      Open Educational Resources free of copyright restrictions.  In the two years that
      courses have been running, 1174 students from 100 countries have registered and
      among the 1597 enrollments in 15 courses, 15% gained a certificate of completion.
      Easily accessible and appealing to a wide geographical and professional audience,
      OOCs have the potential to play a part in establishing global Public Health
      capacity building programmes.

PMID- 28491284
TI  - Hermaphroditism in the white spot grouper Epinephelus coeruleopunctatus (Pisces:
      Serranidae) harvested from Padang City waters, Indonesia.
AB  - The objective of the present study was to determine the length (mm) for sex
      transformation of hermaphroditism in white spot grouper Epinephelus
      coeruleopunctatus as a basis for developing breeding technology. Fish sampling
      was carried out between April and October 2013 in Padang City waters, Indonesia.
      A total of 56 white spot groupers were recorded during the study; of these 22
      were male, 28 female and 6 samples were not recognized regarding sex preference.
      Sex differentiation was detected at a length of 183 mm, and at this size the fish
      are female. Sex transformation to male begun to occur at 302 mm total length.

PMID- 28491285
TI  - Midlife interventions are critical in prevention, delay, or improvement of
      Alzheimer's disease and vascular cognitive impairment and dementia.
AB  - The basic strategy for focusing exclusively on genetically identified targets for
      intervening in late life dementias was formulated 30 years ago.  Three decades
      and billions of dollars later, all efforts at disease-modifying interventions
      have failed.  Over that same period, evidence has accrued pointing to dementias
      as late-life clinical phenotypes that begin as midlife pathologies.  Effective
      prevention therefore may need to begin in midlife, in order to succeed. No
      current interventions are sufficiently safe to justify their use in midlife
      dementia prevention trials.  Observational studies could be informative in
      testing the proposal that amyloid imaging and APOEepsilon 4 genotype can predict
      those who are highly likely to develop Alzheimer's disease and in whom higher
      risk interventions might be justifiable. A naturally occurring, diet-responsive
      cognitive decline syndrome occurs in canines that closely resembles human
      Alzheimer's.  Canine cognitive dysfunction could be useful in estimating how
      early intervention must begin in order to succeed.  This model may also help
      identify and assess novel targets and strategies.  New approaches to dementia
      prevention are urgently required, since none of the world's economies can sustain
      the costs of caring for this epidemic of brain failure that is devastating half
      of the over 85-year-olds globally.

PMID- 28491286
TI  - Unwinding focal segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) represents the most common primary
      glomerular disease responsible for the development of end-stage renal disease
      (ESRD) in the United States (US). The disease progresses from podocyte injury to
      chronic kidney disease (CKD), ultimately leading to total nephron degeneration.
      Extensive basic science research has been conducted to unwind the mechanisms of
      FSGS and, with those insights, understand major contributors of CKD in general.
      As a result, several putative molecules and pathways have been studied, all
      implicated in the disease; some serve, in addition, as early biomarkers. The
      ongoing research is currently focusing on understanding how these molecules and
      pathways can interplay and be utilized as potential diagnostic and therapeutic
      targets. Among these molecules, the soluble urokinase plasminogen activating
      receptor (suPAR) has been studied in detail, both clinically and from a basic
      science perspective. By now, it has emerged as the earliest and most robust
      marker of future CKD. Other circulating factors harming podocytes include anti
      CD40 auto-antibody and possibly cardiotrophin-like cytokine factor-1.
      Understanding these factors will aid our efforts to ultimately cure FSGS and
      possibly treat a larger portion of CKD patients much more effectively.

PMID- 28491287
TI  - Linking cortical microtubule attachment and exocytosis.
AB  - Exocytosis is a fundamental cellular process whereby secreted molecules are
      packaged into vesicles that move along cytoskeletal filaments and fuse with the
      plasma membrane. To function optimally, cells are strongly dependent on precisely
      controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve
      as major tracks for vesicle transport by motor proteins, and thus microtubule
      organization is important for targeted delivery of secretory carriers. Over the
      years, multiple microtubule-associated and cortical proteins have been discovered
      that facilitate the interaction between the microtubule plus ends and the cell
      cortex. In this review, we focus on mammalian protein complexes that have been
      shown to participate in both cortical microtubule capture and exocytosis, thereby
      regulating the spatial organization of secretion. These complexes include
      microtubule plus-end tracking proteins, scaffolding factors, actin-binding
      proteins, and components of vesicle docking machinery, which together allow
      efficient coordination of cargo transport and release.

PMID- 28491290
TI  - DNA nanochannels.
AB  - Transmembrane proteins are mostly nanochannels playing a highly important role in
      metabolism. Understanding their structures and functions is vital for revealing
      life processes. It is of fundamental interest to develop chemical devices to
      mimic biological channels. Structural DNA nanotechnology has been proven to be a
      promising method for the preparation of fine DNA nanochannels as a result of the
      excellent properties of DNA molecules. This review presents the development
      history and current situation of three different types of DNA nanochannel: tile
      based nanotube, DNA origami nanochannel, and DNA bundle nanochannel.

PMID- 28491288
TI  - Selective vulnerabilities and biomarkers in neurocognitive aging.
AB  - As the world's population continues to age, an understanding of the aging brain
      becomes increasingly crucial. This review focuses on several recent ideas and
      findings in the study of neurocognitive aging, specifically focusing on episodic
      memory, and discusses how they can be considered and used to guide us moving
      forward. Topics include dysfunction in neural circuits, the roles of neurogenesis
      and inhibitory signaling, vulnerability in the entorhinal cortex, individual
      differences, and comorbidities. These avenues of study provide a brief overview
      of promising themes in the field and together provide a snapshot of what we
      believe will be important emerging topics in selective vulnerabilities in the
      aging brain.

PMID- 28491289
TI  - Recent advances in preoperative management of esophageal adenocarcinoma.
AB  - Esophageal cancer is an aggressive malignancy with increasing incidence, and the
      prognosis of patients treated by surgery alone remains dismal. Preoperative
      treatment can modestly prolong overall survival. Preoperative chemotherapy or
      chemoradiation is the standard of care for resectable esophageal cancer (greater
      than clinical stage I and less than clinical stage IV). One of the challenges is
      to predict complete response in the surgical specimen from preoperative therapy
      and to avoid surgery in some patients but also predict ineffectiveness of
      preoperative therapy if the tumor is resistant and avoid such therapies
      altogether. In-depth understanding of the molecular biology could lead to
      personalized therapy, and in the future, clinical trials designed according to
      molecular features are expected. Here, we summarize preoperative treatment for
      esophageal adenocarcinoma and their potential.

PMID- 28491291
TI  - Recent advances in the management and understanding of macular degeneration.
AB  - Current management of age-related macular degeneration (AMD) is directed at
      intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors
      for the treatment of wet AMD and supplementation with oral antioxidants for the
      treatment of dry AMD. In this article, we will review recent clinical trials for
      the treatment of dry and wet AMD.

PMID- 28491293
TI  - What's new in the management of adult bronchiectasis?
AB  - Bronchiectasis is a heterogeneous, chronic condition with many aetiologies. It
      poses a significant burden on patients and healthcare practitioners and services.
      Clinical exacerbations often result in reduced quality of life, increased rate of
      lung function decline, increased hospitalisation, and mortality. Recent focus in
      respiratory research, guidelines, and future management options has improved this
      clinical field in evidence-based practice, but further work and phase III
      clinical trials are required. This article aims to summarise and explore advances
      in management strategies in recent years and highlight areas of research and
      future focus.

PMID- 28491294
TI  - Prevalence and pattern of antibiotic resistance of Staphylococcus aureus isolated
      from door handles and other points of contact in public hospitals in Ghana.
AB  - BACKGROUND: Studies have implicated Staphylococcus aureus as the leading cause of
      septicemia in the Tamale metropolis of Ghana. The aim of this study was to
      determine the prevalence and antibiotic susceptibility of S. aureus and
      Methicillin Resistant S. aureus (MRSA) in the environments of three hospitals in
      Ghana. METHODS: A total of 120 swab samples were taken from door handles, stair
      railings and other points of contact at Tamale Teaching Hospital, Tamale Central
      Hospital and Tamale West Hospital. The swab samples were directly plated on
      Mannitol Salt and Baird Parker agar plates and incubated at 37  degrees C (+/- 2)
      for 18-24 h. An antibiotic susceptibility test was performed using the Clinical
      Laboratory Standard Institute's guidelines. Isolates resistant to both cefoxitin
      and oxacillin were considered to be MRSA. RESULTS: A total of 47 (39%) positive
      S. aureus samples were isolated from all three hospitals, of which, eight (17%)
      were putative MRSA isolates. One MRSA isolate was resistant to all the
      antibiotics used (cefoxitin, oxacillin, ciprofloxacin, erythromycin,
      tetracycline, ampicillin, streptomycin and sulfamethoxazole-trimethoprim). Five
      of the MRSA isolates were multi-drug resistant, whilst the other three were
      resistant to only two antibiotics. All the multi-drug resistant MRSA isolates
      were resistant to at least four antibiotics. The percentage of isolates resistant
      to oxacillin, ampicillin, ciprofloxacin, tetracycline, streptomycin,
      erythromycin, and sulfamethoxazole/trimethoprim were 17, 13, 9, 28, 89, 13 and
      11% respectively. CONCLUSION: The high multi-drug resistance of MRSA in hospital
      environments in Ghana reinforces the need for the effective and routine cleaning
      of door handles in hospitals. Further investigation is required to understand
      whether S. aureus from door handles could be the possible causes of nosocomial
      diseases in the hospitals.

PMID- 28491292
TI  - Looking at the recent advances in understanding alpha-synuclein and its
      aggregation through the proteoform prism.
AB  - Despite attracting the close attention of multiple researchers for the past 25
      years, alpha-synuclein continues to be an enigma, hiding sacred truth related to
      its structure, function, and dysfunction, concealing mechanisms of its
      pathological spread within the affected brain during disease progression, and,
      above all, covering up the molecular mechanisms of its multipathogenicity, i.e.
      the ability to be associated with the pathogenesis of various diseases. The goal
      of this article is to present the most recent advances in understanding of this
      protein and its aggregation and to show that the remarkable structural,
      functional, and dysfunctional multifaceted nature of alpha-synuclein can be
      understood using the proteoform concept.

PMID- 28491295
TI  - Magnetic resonance imaging planning in children with complex congenital heart
      disease - A new approach.
AB  - OBJECTIVES: To compare a standard sequential 2D Planning Method (2D-PM) with a 3D
      offline Planning Method (3D-PM) based on 3D contrast-enhanced magnetic resonance
      angiography (CE-MRA) in children with congenital heart disease (CHD). DESIGN: In
      14 children with complex CHD (mean: 2.6 years, range: 3 months to 7.6 years),
      axial and coronal cuts were obtained with single slice spin echo sequences to get
      the final double oblique longitudinal cut of the targeted anatomical structure
      (2D-PM, n = 31). On a separate workstation, similar maximal intensity projection
      (MIP) images were generated offline from a 3D CE-MRA. MIP images were localizers
      for repeated targeted imaging using the previous spin echo sequence (3D-PM).
      Finally, image coverage, spatial orientation and acquisition time were compared
      for 2D-PM and 3D-PM. MAIN OUTCOME MEASURES: 2D-PM and 3D-PM images were similar:
      both perfectly covered the selected anatomic regions and no spatial differences
      were found (p>0.05). The mean time for creation of the final imaging plane was
      241 +/- 31 s (2D-PM) compared to 71 +/- 18 s (3D-PM) (p<0.05). CONCLUSIONS: 3D-PM
      shows similar results compared to 2D-PM, but allows faster and offline planning
      thereby reducing the scan time significantly. As newly developed high-resolution
      3D datasets can also be used further improvement of this technology is expected.

PMID- 28491296
TI  - Assessment of the 10-year risk of cardiovascular disease among a group of
      patients on maintenance hemodialysis: A cross-sectional study from Cameroon.
AB  - OBJECTIVE: To assess the 10-year risk of cardiovascular disease and potential
      impacting factors among patients undergoing hemodialysis in Yaounde, Cameroon.
      DESIGN: A cross-sectional study in January 2016. SETTING: Patients were recruited
      at the dialysis unit of the Yaounde University Teaching Hospital, Cameroon.
      PARTICIPANTS: These were hemodialysis patients aged 20 years and above, dialyzing
      in the above unit since at least 3 months and volunteering to be enrolled in the
      study. MAIN OUTCOME MEASURES: The risk of cardiovascular disease was assessed
      using the Framingham risk score. RESULTS: We included 44 patients. The risk of
      cardiovascular disease ranged from less than 1% to more than 30% with a median of
      12.3% (interquartile range 4.9-24.4). Twenty hemodialysis patients (45.5%) had a
      low risk of cardiovascular disease (<10%), 10 (22.7%), a moderate risk (10-20%),
      and 14 (31.8%) presented a high risk of cardiovascular disease (>20%). In
      multivariable linear regression analysis, duration on dialysis (adjusted beta =
      0.11; p = 0.003), number of weekly sessions of physical activity (adjusted beta =
      -1.35; p = 0.018), fasting serum glucose levels (adjusted beta = 4.22; p =
      0.022), serum triglycerides levels (adjusted beta = 5.94; p = 0.033), and serum
      urea levels (adjusted beta = -2.08; p = 0.039) were independently impacting our
      patients' risk of cardiovascular disease. CONCLUSION: Around 55% of our study
      population presented a moderate or high risk of cardiovascular disease. Duration
      on dialysis, number of physical activity sessions per week, fasting serum
      glucose, serum triglycerides, and serum urea levels may impact our hemodialysis
      patients' risk of cardiovascular disease.

PMID- 28491298
TI  - Low back pain clinical guidelines: similarities and divergent views across the
      pond.

PMID- 28491297
TI  - Net energy of corn, soybean meal and rapeseed meal in growing pigs.
AB  - BACKGROUND: Two experiments were conducted to estimate the net energy (NE) of
      corn, soybean meal, expeller-pressed rapeseed meal (EP-RSM) and solvent-extracted
      rapeseed meal (SE-RSM) using indirect calorimetry and to validate the NE of these
      four ingredients using pig growth performance. METHODS: In Exp.1, 24 barrows
      (initial BW = 36.4 +/- 1.6 kg) were allotted to 1 of 4 diets which included a
      corn basal diet, a corn-soybean meal basal diet and two rapeseed meal diets
      containing 20% EP-RSM (9.5% ether extract) or SE-RSM (1.1% ether extract)
      substituted for corn and soybean meal. The design allowed the calculation of NE
      values of corn, soybean meal and rapeseed meals according to the difference
      method. In Exp.2, 175 growing pigs (initial BW = 36.0 +/- 5.2 kg) were fed 1 of 5
      diets for 28 d, with five pigs per pen and seven replications (pens) per
      treatment in order to validate the measured energy values. Diets were a corn
      soybean meal diet and four diets including 10% or 20% EP-RSM and 10% or 20% SE
      RSM. RESULTS: The NE of corn, soybean meal, EP-RSM and SE-RSM were 12.46, 11.34,
      11.71 and 8.83 MJ/kg DM, respectively. The NE to ME ratio of corn (78%) was
      similar to tabular values, however, the NE to ME ratios of soybean meal (70%) and
      rapeseed meal (76%) were greater than tabular values. The greater NE value in EP
      RSM than in SE-RSM is consistent with its higher EE content. Increasing EP-RSM or
      SE-RSM did not affect the growth performance of pigs and the caloric efficiency
      of NE was comparable for all diets. CONCLUSIONS: The NE of EP-RSM was similar to
      soybean meal, and both were greater than SE-RSM. The DE, ME and NE values
      measured in Exp.1 are confirmed by results of Exp. 2 with comparable caloric
      efficiencies of DE, ME or NE for all diets.

PMID- 28491299
TI  - Contextual modulation of pain sensitivity utilising virtual environments.
AB  - BACKGROUND: Investigating psychological mechanisms that modulate pain, such as
      those that might be accessed by manipulation of context, is of great interest to
      researchers seeking to better understand and treat pain. The aim of this study
      was to better understand the interaction between pain sensitivity, and contexts
      with inherent emotional and social salience - by exploiting modern immersive
      virtual reality (VR) technology. METHODS: A within-subjects, randomised, double
      blinded, repeated measures (RM) design was used. In total, 25 healthy
      participants were exposed to neutral, pleasant, threatening, socially positive
      and socially negative contexts, using an Oculus Rift DK2. Pressure pain
      thresholds (PPTs) were recorded in each context, as well as prior to and
      following the procedure. We also investigated whether trait anxiety and pain
      catastrophisation interacted with the relationship between the different contexts
      and pain. RESULTS: Pressure pain sensitivity was not modulated by context (p =
      0.48). Anxiety and pain catastrophisation were not significantly associated with
      PPTs, nor did they interact with the relationship between context and PPTs.
      CONCLUSION: Contrary to our hypothesis, socially and emotionally salient contexts
      did not influence pain thresholds. In light of other research, we suggest that
      pain outcomes might only be tenable to manipulation by contextual cues if they
      specifically manipulate the meaning of the pain-eliciting stimulus, rather than
      manipulate psychological state generally - as per the current study. Future
      research might exploit immersive VR technology to better explore the link between
      noxious stimuli and contexts that directly alter its threat value.

PMID- 28491300
TI  - Schoolbags and back pain in children between 8 and 13 years: a national study.
AB  - Schoolbag weight in schoolchildren is a recurrent and contentious issue within
      the educational and health sphere. Excessive schoolbag weight can lead to back
      pain in children, which increases the risk of chronic back pain in adulthood.
      There is limited research regarding this among the Maltese paediatric population.
      A cross-sectional study was undertaken across all schools in Malta among students
      aged 8-13 years (inclusive). Data were collected using a questionnaire detailing
      schoolbag characteristics, self-reported pain and demographic variables, such as
      age and gender. Structured interviews with participants were also carried out by
      physiotherapists. A total of 4005 participants were included in the study, with
      20% of the total Malta schoolchildren population. Over 70% of the subjects had a
      schoolbag that exceeded the recommended 10% bag weight to body ratio. A total of
      32% of the sample complained of back pain, with 74% of these defining it as low
      in intensity on the face pain scale-revised. The presence of back pain was
      statistically related to gender, body mass index (BMI), school and bag weight to
      body weight ratio. After adjusting for other factors, self-reported back pain in
      schoolchildren is independently linked to carrying heavy schoolbags. This link
      should be addressed to decrease the occurrence of back pain in this age group.

PMID- 28491301
TI  - Short- and long-term results of an inpatient programme to manage Complex Regional
      Pain Syndrome in children and adolescents.
AB  - The aim of this retrospective study was to determine whether an inpatient
      approach and the use of regional anaesthesia techniques can accelerate the
      recovery to normal functions in children with Complex Regional Pain Syndrome
      (CRPS). This study looked at the data of patients admitted to the rehabilitation
      unit with a diagnosis of CRPS from January 2010 to April 2015. Variables such as
      hospital stay, medications administered, regional anaesthesia procedures, changes
      in functional status prior to treatment and at the time of discharge,
      psychological evaluation and diagnosis were evaluated. A total of 31 patients (21
      females and 10 males) were admitted with a diagnosis of CRPS 1 and 2. In all, 97%
      of the patients received a peripheral or central nerve catheter for an average of
      4 days with pain scores of Verbal Numeric Scale (VNS) score = 1.0 +/- 0.7 and an
      average length of hospital stay of 8.2 +/- 2.6 days. The modified Functional
      Independence Measure for Children (WeeFIM) scores and Canadian Association of
      Occupational Therapists tests significantly improved at the time of hospital
      discharge, as well as their pain scores, which decreased from 8.2 +/- 2 to 1.6 +/
      3. In conclusion, these data suggest that the use of regional anaesthesia
      techniques and an intensive inpatient rehabilitation programme could accelerate
      the recovery of children with CRPS.

PMID- 28491302
TI  - Fibromyalgia in Behcet's disease: a narrative review.
AB  - INTRODUCTION: Fibromyalgia is characterised by chronic widespread pain and
      tenderness. It has often been reported to occur concomitantly with chronic
      rheumatological conditions. Behcet's disease is a chronic relapsing, multisystem,
      autoinflammatory disease. There is only limited understanding of a potential
      relationship between fibromyalgia and Behcet's disease. AIM: Given the potential
      detrimental influence of pain on the outcome of chronic disease, the aim of this
      narrative review is to gain an understanding of the incidence and presentation of
      fibromyalgia in Behcet's disease. METHODS: Electronic databases Scopus, Medline,
      PubMed and UpToDate were searched. RESULTS: A total of 269 studies were
      identified, and limitations and exclusion/inclusion criteria were applied to
      ensure accurate and comparable selection of studies; four studies were selected.
      All cases were assessed for the presence of fibromyalgia according to the 1990 or
      2010 diagnostic criteria of the American College of Rheumatology, with Behcet's
      disease diagnosed according to the International Study Group (ISG) for Behcet's
      disease criteria. A higher prevalence of fibromyalgia (5.7-37.1%) was reported in
      Behcet's disease compared to that of the general population (2.9-4.7%).
      DISCUSSION: While an increased prevalence of fibromyalgia was found in patients
      with Behcet's disease, this needs to be considered within the context of limited
      available evidence. The potential impact of these conditions on the disease
      activity of each other is not clear and may require a prospective study.
      CONCLUSION: Fibromyalgia appears to be more prevalent in those with Behcet's
      disease than would be expected in the overall population. Significance: This
      review provides some evidence that fibromyalgia is more prevalent in those with
      Behcet's disease. To ensure appropriate patient treatment choices, it is
      important that both conditions are diagnosed where they co-exist.

PMID- 28491303
TI  - Self-evaluation of tobacco exposure by allied health students in a community
      college setting.
AB  - OBJECTIVE: Tobacco education is among the initiatives encouraged for health
      professionals to help them appreciate the significance of addressing tobacco use
      among their patients. In this pilot study, a nicotine biomarker (cotinine) study
      was introduced to an applied microbiology course required of all allied health
      students. Participants assessed their own smoking status in the previous 24 h
      using a two-dimensional experimental design of a questionnaire and rapid urinary
      cotinine immunoassay. The study goals were >90% participation of the home
      administered assay and high correlation of the results to cotinine standards.
      Allied health students (medical assistants, respiratory therapists, surgical
      technicians) were selected as the initial test group. METHODS: The study was
      initiated 10 months after the college became 100% tobacco free. Participants were
      initially trained on the use and interpretation of the rapid cotinine test using
      three cotinine standards (0, 400, and 2000 ng/mL urine). Participants
      subsequently tested their own first-morning urine sample at home and then
      answered a questionnaire about their tobacco smoke (and/or nicotine) exposure in
      the previous 24-h period. RESULTS: The cotinine laboratory was offered to a total
      of 161 students (88% female) over 24 months. Participants who reported no
      exposure to a nicotine product in any venue made up 55% of the group. Daily
      smokers made up 17% of the study participants as confirmed by their elevated
      cotinine levels (greater than 100 ng/mL urine). The remaining participants (28%)
      either resided with smokers and/or rode in an automobile with an individual
      smoking in the previous 24 h. Their cotinine levels were moderately elevated in
      some cases, particularly if they had ridden in a car with a smoker. CONCLUSION:
      The pilot study met our objectives of >90% participation and high correlation of
      urinary cotinine levels with questionnaire self-reports.

PMID- 28491304
TI  - Health care to empower self-care in adolescents with type 1 diabetes mellitus and
      an immigrant minority background.
AB  - BACKGROUND: The pediatric diabetes team aims to support health, quality of life,
      and normal growth and development among adolescents with type 1 diabetes
      mellitus. Adolescents with an immigrant background have been found less
      successful in self-care. Previous research indicated that adolescents who had
      integrated the disease as a part of their self-image reasoned differently about
      their self-care to those who had not. OBJECTIVE: The aim of this study was to
      identify elements in the patient-pediatrician consultations that might influence
      such integration of the disease among adolescents with type 1 diabetes mellitus.
      METHODS: A total of 12 pediatrician-adolescent consultations were video-recorded
      and analyzed. The adolescents all had an immigrant background. RESULTS:
      Integration of the disease appeared enabled when responsibility was shared; when
      hope, autonomy, and emotions were confirmed; and when the pediatrician asked
      probing questions. Letting objective data dominate the adolescent's experiences,
      using risk as a motivator, neutralizing emotions in relation to having diabetes,
      and confirming forgetfulness, may instead inhibit disease integration.
      CONCLUSION: An extended person-centered approach with focus on the adolescent's
      experiences of everyday life with a chronic disease and less attention on
      physical parameters in the pediatrician-adolescent consultations may increase
      integration of the disease.

PMID- 28491306
TI  - Association of provider opioid prescribing practices and the Centers for Medicare
      and Medicaid Services hierarchical condition category score: A retrospective
      examination of correlation between the volume of provider-prescribed opioid
      medications and provider panel complexity.
AB  - OBJECTIVE: Opioids are being prescribed at increasing rates in primary care
      practices, and among individual providers there is significant variability in
      opioid prescribing. Primary care practices also vary significantly in complexity
      of their patients, ranging from healthy patients to those with multiple
      comorbidities. Our objective was to examine individual primary care providers for
      an association between their opioid prescribing and the complexity/risk of their
      panel of patients (a panel of patients is a group of patients whose medical care
      is the responsibility of a specific healthcare provider or care team). METHODS:
      We retrospectively examined 12 months of opioid prescription data from a primary
      care practice. We obtained counts of opioids prescribed by providers in the Mayo
      Clinic, Rochester, Minnesota primary care practice. For patients paneled
      (assigned) to family medicine and internal medicine, we used the Centers for
      Medicare and Medicaid Services hierarchical condition category patient risk score
      as a measure of patient complexity. After adjusting the opioid counts for panel
      patient count (to get opioid counts per patient), we used linear regression
      analysis to determine the correlation between the hierarchical condition category
      risk and the amount of opioid prescribed by individual providers. RESULTS: Among
      our combined 103 primary care providers, opioid unit counts prescribed per
      patient were highly correlated with the providers' hierarchical condition
      category panel risk score (r2 = 0.54). After excluding three outliers, r2 was
      0.74. With and without the outliers, the correlation was very significant (p <
      0.0001). Subgroup analysis of panels with hierarchical condition category ? 0.45
      showed no correlation of opioid prescribing volume with hierarchical condition
      category (r2 < 0.02; p = 0.32). Provider panels with hierarchical condition
      category > 0.45 showed significant correlation with hierarchical condition
      category (r2 = 0.26; p = 0.001). CONCLUSION: When examining differences in
      primary care providers' opioid prescribing practices, the Centers for Medicare
      and Medicaid Services endorsed risk score (the hierarchical condition category
      score) can help adjust for population differences of a provider's patients.

PMID- 28491305
TI  - Effects of carvedilol on structural and functional outcomes and plasma biomarkers
      in the mouse transverse aortic constriction heart failure model.
AB  - INTRODUCTION: Despite the widespread use of the mouse transverse aortic
      constriction heart failure model, there are no reports on the characterization of
      the standard-of-care agent carvedilol in this model. METHODS: Left ventricular
      pressure overload was produced in mice by transverse aortic constriction between
      the innominate and left common carotid arteries. Carvedilol was administered at
      multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean
      plasma concentrations of 0.002, 0.015 and 0.044 uM, respectively) in a
      therapeutic design protocol with treatment initiated after the manifestation of
      left ventricular remodeling at 3 weeks post transverse aortic constriction and
      continued for 10 weeks. RESULTS: Carvedilol treatment in transverse aortic
      constriction mice significantly decreased heart rate and left ventricular dP/dt
      (max) at all dose levels consistent with beta-adrenoceptor blockade. The middle
      dose of carvedilol significantly decreased left ventricular weight, whereas the
      higher dose decreased total heart, left and right ventricular weight and wet lung
      weight compared to untreated transverse aortic constriction mice. The higher dose
      of carvedilol significantly increased cardiac performance as measured by ejection
      fraction and fractional shortening and decreased left ventricular end systolic
      volume consistent with the beneficial effect on cardiac function. End-study
      plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic
      constriction control and transverse aortic constriction carvedilol groups. Plasma
      brain natriuretic peptide concentrations were elevated significantly in
      transverse aortic constriction control animals (~150%) compared to shams in
      association with changes in ejection fraction and heart weight and tended to
      decrease (~30%, p = 0.10-0.12) with the mid- and high-dose carvedilol treatment.
      CONCLUSION: A comparison of carvedilol hemodynamic and structural effects in the
      mouse transverse aortic constriction model versus clinical use indicates a strong
      agreement in effect profiles preclinical versus clinical, providing important
      translational validation for this widely used animal model. The present plasma
      brain natriuretic peptide biomarker findings support the measurement of plasma
      natriuretic peptides in the mouse transverse aortic constriction model to extend
      the translational utility of the model.

PMID- 28491307
TI  - Better, Sooner, More Convenient? The reality of pursuing greater integration
      between primary and secondary healthcare providers in New Zealand.
AB  - OBJECTIVES: This article focuses on the results of evaluations of two business
      plans developed in response to a policy initiative which aimed to achieve greater
      integration between primary and secondary health providers in New Zealand. We
      employ the Consolidated Framework for Implementation Research to inform our
      analysis. The Better, Sooner, More Convenient policy programme involved the
      development of business plans and, within each business plan, a range of areas of
      focus and associated work-streams. METHODS: The evaluations employed a mixed
      method multi-level case study design, involving qualitative face-to-face
      interviews with front-line staff, clinicians and management in two districts, one
      in the North Island and the other in the South Island, and an analysis of routine
      data tracked ambulatory sensitive hospitalisations and emergency department
      presentations. Two postal surveys were conducted, one focussing on the patient
      care experiences of integration and care co-ordination and the second focussing
      on the perspectives of health professionals in primary and secondary settings in
      both districts. RESULTS: Both evaluations revealed non-significant changes in
      ambulatory sensitive hospitalisations and emergency department presentation rates
      and slow uneven progress with areas of focus and their associated work-streams.
      Our evaluations revealed a range of implementation issues, the barriers and
      facilitators to greater integration of healthcare services and the implications
      for those who were responsible for putting policy into practice. CONCLUSION: The
      business plans were shown to be overly ambitious and compromised by the size and
      scope of the business plans; dysfunctional governance arrangements and associated
      accountability issues; organisational inability to implement change quickly with
      appropriate and timely funding support; an absence of organisational structural
      change allowing parity with the policy objectives; barriers that were encountered
      because of inadequate attention to organisational culture; competing additional
      areas of focus within the same timeframe; and consequent overloading of front
      line staff which led to workload stress, fatigue and disillusionment. Where
      success was achieved, this largely hinged on the enthusiasm of a small pool of
      front-line workers and their initial buy-into the idea of integrated care.

PMID- 28491308
TI  - Novel combined patient instruction and discharge summary tool improves timeliness
      of documentation and outpatient provider satisfaction.
AB  - BACKGROUND: Incomplete or delayed access to discharge information by outpatient
      providers and patients contributes to discontinuity of care and poor outcomes.
      OBJECTIVE: To evaluate the effect of a new electronic discharge summary tool on
      the timeliness of documentation and communication with outpatient providers.
      METHODS: In June 2012, we implemented an electronic discharge summary tool at our
      145-bed university-affiliated Veterans Affairs hospital. The tool facilitates
      completion of a comprehensive discharge summary note that is available for
      patients and outpatient medical providers at the time of hospital discharge.
      Discharge summary note availability, outpatient provider satisfaction, and time
      between the decision to discharge a patient and discharge note completion were
      all evaluated before and after implementation of the tool. RESULTS: The
      percentage of discharge summary notes completed by the time of first post
      discharge clinical contact improved from 43% in February 2012 to 100% in
      September 2012 and was maintained at 100% in 2014. A survey of 22 outpatient
      providers showed that 90% preferred the new summary and 86% found it
      comprehensive. Despite increasing required documentation, the time required to
      discharge a patient, from physician decision to discharge note completion,
      improved from 5.6 h in 2010 to 4.1 h in 2012 (p = 0.04), and to 2.8 h in 2015 (p
      < 0.001). CONCLUSION: The implementation of a novel discharge summary tool
      improved the timeliness and comprehensiveness of discharge information as needed
      for the delivery of appropriate, high-quality follow-up care, without adversely
      affecting the efficiency of the discharge process.

PMID- 28491310
TI  - Achieving optimal technology use: A proposed model for health technology
      reassessment.
AB  - BACKGROUND: Healthcare providers, managers and policy-makers in many
      jurisdictions are focused on a common goal: optimizing value and quality of care
      provided to their citizens within a resource envelope. Health technology
      reassessment is a structured, evidence-based assessment of the clinical, social,
      ethical and economic effects of a technology currently used in the healthcare
      system to inform optimal use of that technology in comparison with its
      alternatives. There are, however, few practical experiences with health
      technology reassessment and, as such, a nascent theoretical and methodological
      base. Health technology reassessment is a key strategy to achieve optimal
      healthcare resource utilization, and establishing a model for health technology
      reassessment is a required methodological step. METHODS AND RESULTS: The purpose
      of this article is to answer three formative questions: (1) What is health
      technology reassessment? (2) When should a health technology reassessment be
      implemented? (3) What is the role of health technology reassessment in evidence
      informed health policy? Finally, we propose a conceptual framework for health
      technology reassessment, which others can modify, adapt, or adopt in their own
      context. The model consists of three broad phases and six iterative stages: (1)
      identification, (2) prioritization, (3) evidence synthesis, (4) determine
      policy/practice recommendation, (5) policy/practice implementation and (6)
      monitoring and evaluation. Two foundational components (meaningful stakeholder
      engagement and ongoing knowledge exchange and utilization) are represented across
      all stages. CONCLUSION: This description of health technology reassessment and
      the proposed model can be used by healthcare policy-makers and researchers to
      advance the field of technology management, with the goal of achieving optimal
      use throughout a technology's lifecycle.

PMID- 28491311
TI  - Does increased standardisation in health care mean less responsiveness towards
      individual patients' expectations? A register-based study in Swedish primary
      care.
AB  - OBJECTIVE: We explore whether standardisation in health care based on evidence on
      group level and a public health perspective is in conflict with responsiveness
      towards individual patient's expectations in Swedish primary care. METHODS: Using
      regression analysis, we study the association between patient views about
      providers' responsiveness and indicators reflecting provider's adherence to
      evidence-based guidelines, controlled for characteristics related to providers,
      including patient mix and degree of competition facing providers. Data were taken
      from two Swedish regions in years 2012 and 2013. RESULTS: Patients' views about
      responsiveness are positively correlated with variables reflecting provider's
      adherence to evidence-based guidelines regarding treatment of elderly and risk
      groups, drug reviews and prescription of antibiotics. A high overall illness,
      private ownership and a high proportion of all visits being with a doctor are
      positively associated with patient views about responsiveness. The opposite
      relation was found for a high social deprivation among enrolled individuals and
      size of practice. There was no systematic variation with respect to the degree of
      competition facing providers. CONCLUSION: Results suggest that responsiveness
      towards individual patient expectations is compatible with increased
      standardisation in health care. This is encouraging for health care providers as
      they are challenged to balance increased demands from both patients and payers.

PMID- 28491312
TI  - Neuroleptic malignant syndrome following catatonia: Vigilance is the price of
      antipsychotic prescription.
AB  - OBJECTIVES: To describe a case of neuroleptic malignant syndrome following
      antipsychotic treatment of catatonia, highlighting the potentially serious
      complications of this rare adverse drug reaction. METHODS: We present a case
      report of a patient who developed this syndrome with various sequelae. RESULTS:
      The patient developed neuroleptic after being treated with lorazepam and
      olanzapine for catatonia. He subsequently developed the complications of
      rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and
      ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids.
      Antipsychotic medication in the form of haloperidol was reinstated with no
      adverse effect, and he went on to make a full recovery. CONCLUSIONS: This case
      illustrates the potential life-threatening complications of neuroleptic malignant
      syndrome and the need for a low index of clinical suspicion. It also highlights
      the lack of evidence for treatment of catatonia, including the use of
      antipsychotics.

PMID- 28491313
TI  - Positron emission tomography imaging in a case of E200K mutation-related
      spongiform encephalopathy with non-diagnostic magnetic resonance imaging and
      cerebrospinal fluid testing.
AB  - OBJECTIVE: Creutzfeldt-Jakob disease is a rapidly progressive spongiform
      encephalopathy. The E200K mutation is found in a majority of genetically
      transmitted Creutzfeldt-Jakob disease cases. METHODS: We describe the case and
      associated neuroimaging of an E200K-129M gene-mutation-related fatal spongiform
      encephalopathy with resultant clinical insomnia and thalamic changes. RESULTS: A
      46-year-old Caucasian male presented with, who was well until 2 months prior to
      admission, a rapidly progressive dementia followed by a change in personality
      with auditory and visual hallucinations. His wife noted progressively worsening
      jerking and other limb movements and that he kept his eyes open overnight and was
      "awake" at all hours. Magnetic resonance imaging, electroencephalogram and
      initial cerebrospinal fluid analysis were essentially non-diagnostic. Positron
      emission topography revealed severe bilateral thalamic hypometabolism. Posthumous
      cerebrospinal fluid analysis revealed abnormal PrP 27-30 protein. Autopsy
      confirmed prion disease and presence of the E200K-129M mutation. CONCLUSION: This
      report highlights that positron emission topography imaging may help diagnose
      E200K-129M mutation-related spongiform encephalopathy. In cases of non-diagnostic
      magnetic resonance imaging, electroencephalogram and cerebrospinal fluid studies,
      early positron emission topography may help in the workup of rapidly progressive
      dementia.

PMID- 28491314
TI  - Major depressive disorder with religious struggle and completed suicide after
      hair transplantation.
AB  - OBJECTIVES: Psychological outcomes of aesthetic surgical procedures like hair
      transplantation are mostly positive including decreased anxiety, depression and
      social phobia and increased general well-being, self-efficacy and self-esteem.
      However, some patients may suffer from post-surgical depression and post-surgical
      increased suicide rates have been reported for breast augmentation patients.
      Difficulty adapting to the new image, unfulfilled psychological needs expected to
      be met by the surgery, side effects of the surgery like tissue swelling or
      bruising, uncontrolled pain, presence of body dysmorphic disorder and previous
      history of mood disorder may be some of the risk factors for post-surgical
      depression. METHODS: Here, we present a case without prior psychiatric history
      who developed major depressive disorder after hair transplantation and died of
      suicide. RESULTS: He started experiencing religious struggle related to his
      decision about the hair transplant which he interpreted as acting against God's
      will. While religious involvement has been reported to be a protective factor
      against depression, spiritual struggle, which includes religious guilt, has been
      described as an important risk factor for depression, hopelessness and
      suicidality which might explain the severity of depression in our patient.
      CONCLUSIONS: This case highlights the importance of a detailed psychiatric
      evaluation and exploration of religious concerns of any patient before any type
      of aesthetic surgery. Major depressive disorder is a treatable condition;
      however, mild depression can go unnoticed. Religious belief and related religious
      practices affect an individual's personal health attitudes; therefore, we think
      that every physician is needed to explore the religious concerns of any patient
      during any medical examination or surgical procedure. Relevant religious
      authorities should be consulted when necessary.

PMID- 28491315
TI  - Subcutaneous dirofilariasis caused by Dirofilaria (Nochtiella) repens in Sri
      Lanka: A potential risk of transmitting human dirofilariasis.
AB  - OBJECTIVE: Dirofilariasis is a parasitic infection caused by filarial nematodes
      belonging to the genus Dirofilaria. Human dirofilariasis due to Dirofilaria
      repens has been widely reported from European countries. Sri Lanka is the most
      affected country in Asia with an infection rate of almost 60% in dog population.
      However, human infection of D. repens remains undiagnosed and many of the cases
      are not scientifically documented. Therefore, the objective of the present
      investigation is to document the presence of dirofilariasis infections in humans.
      METHOD: A 1 year and 10 months old boy from Ragama, Gampaha District, Western
      Province of Sri Lanka, was presented to a private hospital with a painless, non
      pruritic and ill-defined subcutaneous nodule on his right hypochondrial region of
      the anterior abdominal wall for 1 week. On examination, there was a non-tender
      swelling measuring 2 cm * 2 cm in the anterior abdominal wall, with surrounding
      mild redness. The patient was referred for ultrasound confirmation. RESULTS: The
      ultrasound scan revealed a hypoechoic nodular lesion measuring 11 mm * 6 mm in
      the anterior abdominal wall. Parasitological examination on the excised nodule
      confirmed the presence of D. repens measuring 10.5 cm in length having
      characteristic cuticle with longitudinal ridges. CONCLUSION: It is essential to
      record the human infections and increase the awareness about this infection,
      diagnostic tests and vector controlling measures, in order to reduce the disease
      prevalence through suppressing vector densities, proper diagnosis and patient
      care.

PMID- 28491316
TI  - Pituitary abscess in an HIV-1-infected patient.
AB  - OBJECTIVES: Pituitary abscess is a rare occurrence among pituitary conditions,
      but one which carries life-threatening potential. An immunocompromised status is
      a risk factor for the development of a pituitary abscess; however, literature
      describes only one case among HIV-infected patients. METHODS AND RESULTS: We
      present here a case of pituitary abscess in an HIV-1-positive patient, who
      demonstrated a shock status, disturbance of consciousness and generalized skin
      rash with laboratory findings of hypovolemia, acute inflammatory reaction and
      blood electrolyte abnormality. We first diagnosed the dermal manifestation as
      atypical generalized zoster, however, the other clinical findings could not be
      explained by VZV infection only. Combination with anamnesis, head magnetic
      resonance imaging scan and endocrine function test helped us to diagnose
      pituitary abscess. Although the etiology of the pituitary abscess could not be
      detected, the patient was successfully treated with antibiotics but followed by
      panhypopituitarism as sequela. CONCLUSION: A pituitary abscess should be
      considered in HIV-infected patients with endocrinological abnormalities, visual
      field defects, and central nervous system infection signs or symptoms, regardless
      of CD4 T-cell counts.

PMID- 28491317
TI  - Marathoning with myotonic dystrophy type 2 (proximal myotonic myopathy) and
      leukopenia.
AB  - OBJECTIVES: A mild, slowly progressive course of proximal myotonic myopathy, also
      known as myotonic dystrophy type 2, over years allowing the patient to continue
      with extreme sport activity, has been only rarely reported. METHODS: Case report.
      RESULTS: The patient is a 54-year-old female sport teacher who developed myotonia
      of the distal upper limbs at the age of 32 years. Over the following 22 years,
      myotonia spreaded to the entire musculature. Myotonia did not prevent her from
      doing her job and from marathoning and improved with continuous exercise.
      Additionally, she had developed hypothyroidism, ovarial cysts, incipient
      cataract, motor neuropathy, hepatopathy, leukopenia, and mild hyper-CK-emia. A
      heterozygous CCTG-repeat expansion of 500-9500 was found in the CNBP/ZNF9 gene.
      At the age of 54 years, she was still performing sport, without presenting with
      myotonia on clinical examination or having developed other typical manifestations
      of proximal myotonic myopathy. CONCLUSIONS: This case shows that proximal
      myotonic myopathy may take a mild course over at least 22 years, that proximal
      myotonic myopathy with mild myotonia may allow a patient to continue strenuous
      sport activity, and that continuous physical activity may contribute to the mild
      course of the disease.

PMID- 28491318
TI  - Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase
      therapy.
AB  - OBJECTIVES: This case report describes two cases of high-dose methotrexate
      induced nephrotoxicity: death in the case of conventional supportive care and
      successful renal function recovery in a patient treated with glucarpidase and
      continuous dialysis. METHODS: High dose methotrexate is widely used for
      management of adult and pediatric malignancies. However, high-dose methotrexate
      induced renal nephrotoxicity may cause severe, even lethal complications. Here we
      present examples of such outcomes. RESULTS: We present one case of lethal high
      dose methotrexate nephrotoxicity in a patient treated with conventional rescue
      therapy. We contrast this outcome with another patient with high-dose
      methotrexate-induced anuric acute kidney injury, who has recovered renal function
      following therapy with glucarpidase and continuous dialysis. CONCLUSIONS: This is
      only the second reported case of high-dose methotrexate-induced anuric acute
      kidney injury, and the only one with a reported clinical outcome. This first
      report of recovery from high-dose methotrexate-induced anuric acute kidney injury
      after glucarpidase administration supports available evidence pointing to the
      effectiveness of this therapy.

PMID- 28491319
TI  - Macroscopic lymphovascular invasion visualized on mammogram and magnetic
      resonance imaging: Initially misidentified as ductal carcinoma in situ but
      properly diagnosed by immunohistochemistry.
AB  - OBJECTIVES: Lymphovascular invasion (LVI) is a pathologic, microscopic finding
      associated with invasive cancer, and is a poor prognostic indicator, but has no
      reported imaging findings. This report presents the first documented case of LVI
      with seen by imaging. Linear branching microcalcifications were identified on
      mammography and clumped enhancement was noted on MRI, both imaging findings that
      are highly predictive of ductal carcinoma in situ (DCIS). METHODS: Ultrasound
      guided core biopsy of the dominant mass was performed, confirming invasive ductal
      malignancy. Stereotactic biopsy performed on the microcalcifications was
      initially interpreted by pathology as DCIS. RESULTS: Patient underwent
      mastectomy. Pathologic evaluation of the surgical specimen confirmed the invasive
      ductal malignancy. Microcalcifications were re-evaluated with
      immunohistochemistry (IHC) and re-classified as LVI. Radiology images and IHC
      stains are shown. CONCLUSION: This is the first report of LVI identified by
      imaging with findings that mimicked DCIS and initially mis-identified as DCIS by
      pathology as well. The implications of this overlap in radiologic appearance are
      discussed.

PMID- 28491320
TI  - Push-pull dioxaborine as fluorescent molecular rotor: far-red fluorogenic probe
      for ligand-receptor interactions.
AB  - Fluorescent solvatochromic dyes and molecular rotors increase their popularity as
      fluorogenic probes for background-free detection of biomolecules in cellulo in no
      wash conditions. Here, we introduce a push-pull boron-containing (dioxaborine)
      dye that presents unique spectroscopic behavior combining solvatochromism and
      molecular rotor properties. Indeed, in organic solvents, it shows strong red
      shifts in the absorption and fluorescence spectra upon increase in solvent
      polarity, typical for push-pull dyes. On the other hand, in polar solvents, where
      it probably undergoes Twisted Intramolecular Charge Transfer (TICT), the dye
      displays strong dependence of its quantum yield on solvent viscosity, in
      accordance to Forster-Hoffmann equation. In comparison to solvatochromic and
      molecular rotor dyes, dioxaborine derivative shows exceptional extinction
      coefficient (120,000 M-1 cm-1), high fluorescence quantum yields and red/far-red
      operating spectral range. It also displays much higher photostability in apolar
      media as compared to Nile Red, a fluorogenic dye of similar color. Its reactive
      carboxy derivative has been successfully grafted to carbetocin, a ligand of the
      oxytocin G protein-coupled receptor. This conjugate exhibits >1000-fold turn on
      between apolar 1,4-dioxane and water. It targets specifically the oxytocin
      receptor at the cell surface, which enables receptor imaging with excellent
      signal-to-background ratio (>130). We believe that presented push-pull
      dioxaborine dye opens a new page in the development of fluorogenic probes for
      bioimaging applications.

PMID- 28491321
TI  - Thermotolerance capacities of native and exotic coastal plants will lead to
      changes in species composition under increased heat waves.
AB  - With an increase in the frequency and intensity of extreme heat events, plants
      are likely to reach their thermal limits and show slower growth or increased
      mortality. We investigated differences amongst coastal native and invasive shrubs
      and grasses to investigate if particular species might be more at risk in the
      future. Using an ecologically relevant experimental set of heat waves over a
      month, we assessed changes in biomass and photosynthetic efficiency in a
      laboratory setting using 25 coastal Australian species divided into native and
      exotic shrubs, and native and exotic grasses. We also compared three C3 and three
      C4 grasses within the native and exotic groups. Overall, native shrubs suffered
      higher mortality, lower growth and increased photosynthetic stress. There was
      some evidence that C3 grasses, had lower growth with heat waves, compared to C4
      species although, in general, grasses showed evidence of photosynthetic
      acclimation over the month. Increases in leaf abscission suggest that part of the
      acclimation process was to develop new, thermally tolerant leaves. Our results
      indicate that in the future we would expect an increase in exotic shrubs and
      grasses occupying spaces in coastal plant communities that arise from native
      mortality following extreme heat events. Management of these coastal communities
      will need to focus strongly on maintaining a diverse native shrub composition
      that can resist climate-based disturbances (such as wildfire), as well as
      controlling the extent and biomass of exotic species, if coastal communities are
      to remain healthy and diverse in a changing climate.

PMID- 28491322
TI  - ERRATUM.
AB  - [This corrects the article DOI: 10.1002/rcr2.230.].

PMID- 28491324
TI  - Giant parathyroid adenoma: differential aspects compared to parathyroid
      carcinoma.
AB  - : The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid
      adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually
      measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually
      exceeds these dimensions and are associated with a severe PHPT. However, giant PA
      (GPA), which is defined as those larger than 3 g, has been documented. Those may
      be associated with very high levels of PTH and calcium. In these cases, their
      differentiation before and after surgery with PC is very difficult. We present a
      case of severe PHPT associated with a large parathyroid lesion, and we discuss
      the differential aspects between the GPA and PC. LEARNING POINTS: In parathyroid
      lesions larger than 2 cm, the differential diagnosis between GPA and PC should be
      considered.Pre and postsurgical differentiation between GPA and PC is difficult;
      however, there are clinical, analytical and radiographic characteristics that may
      be useful.The depth/width ratio larger or smaller than 1 seems to be the most
      discriminatory ultrasound parameter for the differential diagnosis.Loss of
      staining for parafibromin has a specificity of 99% for the diagnosis of PC.The
      simultaneous presence of several histological characteristics, according to the
      classification of Schantz and Castleman, is frequent in PC and rare in GPA.

PMID- 28491326
TI  - NMNI editorial report, 2016.

PMID- 28491325
TI  - Propionimicrobium lymphophilum and Actinotignum schaalii bacteraemia: a case
      report.
AB  - Propionimicrobium lymphophilum is an anaerobic Gram-positive bacillus that exists
      in human skin and urinary tract. The pathogenicity is, however, not well known.
      Only two cases of urinary tract infection have been described recently. In the
      case presented here, the bacterium was isolated, concomitant with Actinotignum
      schaalii, from blood culture of a patient with fever and difficulty of urination.
      The bacteria were identified by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry and 16S rRNA sequencing. The case was successfully
      treated with ampicillin/sulbactam.

PMID- 28491323
TI  - Interactions between oestrogen and 1alpha,25(OH)2-vitamin D3 signalling and their
      roles in spermatogenesis and spermatozoa functions.
AB  - Oestrogens and 1alpha,25(OH)2-vitamin D3 (1,25-D3) are steroids that can provide
      effects by binding to their receptors localised in the cytoplasm and in the
      nucleus or the plasma membrane respectively inducing genomic and non-genomic
      effects. As confirmed notably by invalidation of the genes, coding for their
      receptors as tested with mice with in vivo and in vitro treatments, oestrogens
      and 1,25-D3 are regulators of spermatogenesis. Moreover, some functions of
      ejaculated spermatozoa as viability, DNA integrity, motility, capacitation,
      acrosome reaction and fertilizing ability are targets for these hormones. The
      studies conducted on their mechanisms of action, even though not completely
      elicited, have allowed the demonstration of putative interactions between their
      signalling pathways that are worth examining more closely. The present review
      focuses on the elements regulated by oestrogens and 1,25-D3 in the testis and
      spermatozoa as well as the interactions between the signalling pathways of both
      hormones.

PMID- 28491327
TI  - Understanding perceived determinants of nurses' eating and physical activity
      behaviour: a theory-informed qualitative interview study.
AB  - BACKGROUND: Unhealthy eating and physical activity behaviours are common among
      nurses but little is known about determinants of eating and physical activity
      behaviour in this population. The present study used a theoretical framework
      which summarises the many possible determinants of different health behaviours
      (the Theoretical Domains Framework; TDF) to systematically explore the most
      salient determinants of unhealthy eating and physical activity behaviour in
      hospital-based nurses. METHODS: Semi-structured qualitative interviews based on
      the TDF were conducted with nurses (n = 16) to explore factors that behavioural
      theories suggest may influence nurses' eating and physical activity behaviour.
      Important determinants of the target behaviours were identified using both
      inductive coding (of categories emerging from the data) and deductive coding (of
      categories derived from the TDF) of the qualitative data. RESULTS: Thirteen of
      the fourteen domains in the TDF were found to influence nurses' eating and
      physical activity behaviour. Within these domains, important barriers to engaging
      in healthy eating and physical activity behaviour were shift work, fatigue,
      stress, beliefs about negative consequences, the behaviours of family and friends
      and lack of planning. Important factors reported to enable engagement with
      healthy eating and physical activity behaviours were beliefs about benefits, the
      use of self-monitoring strategies, support from work colleagues, confidence,
      shift work, awareness of useful guidelines and strategies, good mood, future
      holidays and receiving compliments. CONCLUSIONS: This study used a theory
      informed approach by applying the TDF to identify the key perceived determinants
      of nurses' eating and physical activity behaviour. The findings suggest that
      future efforts to change nurses' eating and physical activity behaviours should
      consider targeting a broad range of environmental, interpersonal and
      intrapersonal level factors, consistent with a socio-ecological perspective.

PMID- 28491328
TI  - Increases in waist circumference independent of weight in Mongolia over the last
      decade: the Mongolian STEPS surveys.
AB  - BACKGROUND: In Mongolia, mean waist circumference (WC) has increased dramatically
      over the last decade, however, it is unknown whether these increases have been
      greater than corresponding increases in weight. In this study we aimed to assess
      whether recent increases in WC were greater than expected from changes in weight
      in Mongolian adults. METHODS: We used data on 13260 Mongolian adults, aged
      between 18 and 64 years, who participated in one of three (2005, 2009, 2013)
      nationally representative cross-sectional surveys. Linear regression was used to
      estimate changes in mean WC over time, adjusted for age, sex, height and weight.
      We also estimated the age-standardised prevalence for four obesity classification
      categories (not obese; obese by WC only; obese by body mass index (BMI) only;
      obese by both BMI and WC) at each survey year. RESULTS: The estimated mean WC in
      2009 and 2013, respectively, was 1.26 cm (95% CI: 0.35 to 2.17) and 1.88 cm (95%
      CI: 1.09 to 2.67) greater compared to 2005, after adjusting for age, sex, height
      and weight. Between 2005 and 2013, the age-standardised prevalence of those obese
      according to both BMI and WC increased from 8.0 to 13.6% for men and from 16.5 to
      25.5% for women. During the same period, the percentage who were obese by WC only
      increased from 1.8 to 4.8% for men and from 16.5 to 26.8% for women. In contrast,
      the percentage who were obese by BMI only remained relatively stable (women: 2.4%
      in 2005 to 1.0% in 2013; men: 2.7% in 2005 to 4.0% in 2013). CONCLUSION: Over the
      last decade, among Mongolian adults, there has been substantially greater
      increase in WC and the prevalence of abdominal obesity than would be expected
      from increases in weight. Women are at greater risk than men of being
      misclassified as not obese if obesity is defined using BMI only. Obesity should
      be monitored using WC in addition to BMI to ensure the prevalence of obesity is
      not underestimated.

PMID- 28491329
TI  - Varicella vasculopathy presenting with thunderclap headache.
AB  - Our report serves to highlight Varicella vasculopathy as a rarity not to be
      overlooked in the differential diagnosis of subarachnoid haemorrhage.

PMID- 28491330
TI  - Duodenal perforation as a complication of gastrostomy tube migration.
AB  - Gastrostomy tube placement is a routinely safe procedure; however, this report
      and its accompanying images highlight a rare but serious complication of tube
      migration - duodenal perforation.

PMID- 28491331
TI  - MPO-C-ANCA-associated necrotising and crescentic glomerulonephritis.
AB  - The patterns of ANCA staining usually relate closely to antibodies against
      myeloperoxidase and proteinase-3. C-ANCA is mainly antibodies to proteinase-3 and
      P-ANCA is antibodies to myeloperoxidase. C-ANCA with antibodies to MPO with
      clinical sequelae is unusual.

PMID- 28491332
TI  - Lipoma in the femoral triangle.
AB  - The differential diagnosis of a lipoma in the femoral region will include a
      femoral hernia and vice-versa or both may coexist.

PMID- 28491333
TI  - Burkholderia cepacia complex and limited cutaneous vasculitis in patients with
      cystic fibrosis: a case series.
AB  - There is a high association of reactive skin presentations, mainly limited
      cutaneous vasculitis in patients with cystic fibrosis and Burkholderia cepcia
      complex chronic infection. This may be due to raised levels of circulating
      inflammatory mediators.

PMID- 28491334
TI  - Increasing the Rate of Living Donor Kidney Transplantation in Ontario: Donor- and
      Recipient-Identified Barriers and Solutions.
AB  - PURPOSE OF REVIEW: To hear from living kidney donors and recipients about what
      they perceive are the barriers to living donor kidney transplantation, and how
      patients can develop and lead innovative solutions to increase the rate and
      enhance the experiences of living donor kidney transplantation in Ontario.
      SOURCES OF INFORMATION: A one-day patient-led workshop on March 10th, 2016 in
      Toronto, Ontario. METHODS: Participants who were previously engaged in priority
      setting exercises were invited to the meeting by patient lead, Sue McKenzie. This
      included primarily past kidney donors, kidney transplant recipients, as well as
      researchers, and representatives from renal and transplant health care
      organizations across Ontario. KEY FINDINGS: Four main barriers were identified:
      lack of education for patients and families, lack of public awareness about
      living donor kidney transplantation, financial costs incurred by donors, and
      health care system-level inefficiencies. Several novel solutions were proposed,
      including the development of a peer network to support and educate patients and
      families with kidney failure to pursue living donor kidney transplantation;
      consistent reimbursement policies to cover donors' out-of-pocket expenses; and
      partnering with the paramedical and insurance industry to improve the efficiency
      of the donor and recipient evaluation process. LIMITATIONS: While there was a
      diversity of experience in the room from both donors and recipients, it does not
      provide a complete picture of the living kidney donation process for all Ontario
      donors and recipients. The discussion was provincially focused, and as such, some
      of the solutions suggested may already be in practice or unfeasible in other
      provinces. IMPLICATIONS: The creation of a patient-led provincial council was
      suggested as an important next step to advance the development and implementation
      of solutions to overcome patient-identified barriers to living donor kidney
      transplantation.

PMID- 28491335
TI  - The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D
      and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study.
AB  - BACKGROUND: Prediction of acute kidney transplant rejection remains imperfect
      despite several known risk factors. There is an increasing appreciation of the
      potential importance of the vitamin D pathway in immunological disease and
      transplantation. OBJECTIVE: The purpose of this study was to determine the
      association of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with acute
      rejection. DESIGN: This was a prospective cohort study. SETTING: Three academic
      adult kidney transplant programs in Ontario, Canada, were chosen. PATIENTS: All
      consecutive adult patients at the 3 institutions who received a solitary kidney
      transplant, were able to provide written informed consent, and planned to be
      followed at the same center post-operatively were included. MEASUREMENTS: Serum
      concentration of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured at
      baseline, 3, and 6 months post-transplantation. Acute rejection was classified
      using Banff criteria. METHODS: The co-primary outcome was the association between
      25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and time to first occurrence of
      biopsy-proven acute rejection (BPAR) within the first year after kidney
      transplantation. Cox proportional hazards models were fitted taking into account
      the time-varying nature of serum concentrations of 25-hydroxyvitamin D and 1,25
      dihydroxyvitamin D. RESULTS: From 556 screened patients, data on 327 kidney
      transplant recipients are included. First BPAR occurred in 54 (16.5%) patients.
      In adjusted Cox proportional hazards models, the serum concentration of 25
      hydroxyvitamin D and 1,25-dihydroxyvitamin D was not associated with acute renal
      transplant rejection (hazard ratio 1.00; 95% [confidence interval] CI, 0.87-1.14,
      per 10 nmol/L increase, and hazard ratio 0.97; 95% CI, 0.84-1.12, per 10 pmol/L
      increase, respectively). LIMITATIONS: Given the observational design, we cannot
      rule out the possibility of residual confounding that limited our ability to
      detect a clinically significant effect of vitamin D metabolites on acute
      rejection. CONCLUSIONS: A low serum concentration of 25-hydroxyvitamin D and 1,25
      dihydroxyvitamin D is not associated with an increased risk of acute kidney
      transplant rejection following kidney transplantation.

PMID- 28491336
TI  - Opportunities for Engaging Patients in Kidney Research.
AB  - PURPOSE: The purpose of this review is to provide a summary of the rationale for
      engaging patients in research as well as to review the established and envisioned
      advantages and strategies for patient-researcher partnerships. The authors of
      this article, which include a patient and 4 researchers in kidney disease,
      discuss the expected benefits and opportunities for patient engagement in their
      respective research programs. The 4 research programs span the spectrum of kidney
      disease and focus on enhancing bone health, increasing living donor kidney
      transplants, improving medication adherence, and preventing kidney transplant
      rejection. SOURCES OF INFORMATION: The sources of information for this review
      include published studies on the topics of patient engagement and the 4 research
      programs of the new investigators. KEY FINDINGS: (1) Patient, health care
      provider, and researcher partnerships can contribute useful insights capable of
      enhancing research in kidney disease. (2) Regardless of the research program,
      there are various strategies and opportunities for engagement of patients with
      lived experience across the various stages of research in kidney disease. (3)
      Envisioned advantages of patient-researcher partnerships include: targeting
      patient-identified research priorities, integrating patients' experiential
      knowledge, improving study design and feasibility through patient-researcher
      input, facilitating dissemination of research findings to other patients,
      effectively responding to patient concerns about studies, and inspiring
      researchers to conduct their research. LIMITATIONS: The limitations of the
      current review include the relative scarcity of literature on patient engagement
      within the field of kidney disease. IMPLICATIONS: The findings of the current
      review suggest that it will be important for future studies to identify optimal
      strategies for patient engagement in setting research priorities, study design,
      participant recruitment, execution of research projects, and knowledge
      dissemination and translation.

PMID- 28491337
TI  - Kidney Disease Among Registered Metis Citizens of Ontario: A Population-Based
      Cohort Study.
AB  - BACKGROUND: Indigenous peoples in Canada have higher rates of kidney disease than
      non-Indigenous Canadians. However, little is known about the risk of kidney
      disease specifically in the Metis population in Canada. OBJECTIVE: To compare the
      prevalence of chronic kidney disease and incidence of acute kidney injury and end
      stage kidney disease among registered Metis citizens in Ontario and a matched
      sample from the general Ontario population. DESIGN: Population-based,
      retrospective cohort study using data from the Metis Nation of Ontario's
      Citizenship Registry and administrative databases. SETTING: Ontario, Canada; 2003
      2013. PATIENTS: Ontario residents >=18 years. MEASUREMENTS: Prevalence of chronic
      kidney disease and incidence of acute kidney injury and end-stage kidney disease.
      Secondary outcomes among patients hospitalized with acute kidney injury included
      non-recovery of kidney function and mortality within 1 year of discharge.
      METHODS: Database codes and laboratory values were used to determine study
      outcomes. Metis citizens were matched (1:4) to Ontario residents on age, sex, and
      area of residence. The analysis included 12 229 registered Metis citizens and 48
      916 adults from the general population. RESULTS: We found the prevalence of
      chronic kidney disease was slightly higher among Metis citizens compared with the
      general population (3.1% vs 2.6%, P = 0.002). The incidence of acute kidney
      injury was 1.2 per 1000 person-years in both Metis citizens and the general
      population (P = 0.54). Of those hospitalized with acute kidney injury, outcomes
      were similar among Metis citizens and the general population except 1-year
      mortality, which was higher for Metis citizens (24.5% vs 15.3%, P = 0.03). The
      incidence of end-stage kidney disease did not differ between groups (<3.0 per 10
      000 person-years, P = 0.73). LIMITATIONS: The Metis Nation of Ontario Citizenship
      Registry only captures about 20% of Metis people in Ontario. Administrative
      health care codes used to identify kidney disease are highly specific but have
      low sensitivity. CONCLUSIONS: Rates of kidney disease were similar or slightly
      higher for Metis citizens in Ontario compared with the matched general
      population.

PMID- 28491338
TI  - Setting New Directions for Research in Childhood Nephrotic Syndrome: Results From
      a National Workshop.
AB  - BACKGROUND: We report on the proceedings of a national workshop held in Canada
      with the aims to identify priorities for research in childhood nephrotic syndrome
      and to develop a national strategy to address these priorities. METHODS: A
      diverse group of participants attended the meeting, including patients, family
      members, researchers, and health care providers. We used small group discussions
      to explore priorities as perceived by patients and families and by health care
      providers and researchers. RESULTS: Research evaluating glucocorticoid
      minimization or glucocorticoid-sparing regimens was a consistent theme in the
      patient and family discussion group. Families also indicated the need for precise
      prognostic information at diagnosis, more information to help them choose the
      best available therapy, and more resources for disease management. Health care
      providers emphasized the importance of better disease characterization including
      genotyping and phenotyping patients, better understanding the pathogenesis, and
      the need of providing targeted therapy and precise prognostic information.
      CONCLUSIONS: These priorities will inform the development and future directions
      of the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project, a national
      research initiative to improve care and outcomes of patients with childhood onset
      nephrotic syndrome.

PMID- 28491339
TI  - The Clinical Epidemiology and 30-Day Outcomes of Emergency Department Patients
      With Acute Kidney Injury.
AB  - BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality and
      dialysis in hospitalized patients but has been little explored in the emergency
      department (ED) setting. OBJECTIVE: The objective of this study was to describe
      the risk factors, prevalence, management, and outcomes in the ED population, and
      to identify the proportion of AKI patients who were discharged home with no renal
      specific follow-up. DESIGN: This is a retrospective cohort study using
      administrative and laboratory databases. SETTING: Two urban EDs in Vancouver,
      British Columbia, Canada. PATIENTS: We included all unique ED patients over a 1
      week period. METHODS: All patients had their described demographics,
      comorbidities, medications, laboratory values, and ED treatments collected. AKI
      was defined pragmatically, based upon accepted guidelines. The cohort was then
      probabilistically linked to the provincial renal database to ascertain renal
      replacement (transplant or dialysis) and the provincial vital statistics database
      to obtain mortality. The primary outcome was the prevalence of AKI; secondary
      outcomes included (1) the proportion of AKI patients who were discharged home
      with no renal-specific follow-up and (2) the combined 30-day rate of death or
      renal replacement among AKI patients. RESULTS: There were 1651 ED unique
      patients, and 840 had at least one serum creatinine (SCr) obtained. Overall, 90
      patients had AKI (10.7% of ED patients with at least one SCr, 95% confidence
      interval [CI], 8.7%-13.1%; 5.5% of all ED patients, 95% CI, 4.4%-6.7%) with a
      median age of 74 and 70% male. Of the 31 (34.4%) AKI patients discharged home, 4
      (12.9%) had renal-specific follow-up arranged in the ED. Among the 90 AKI
      patients, 11 died and none required renal replacement at 30 days, for a combined
      outcome of 12.2% (95% CI, 6.5%-21.2%). LIMITATIONS: Sample sizes may be small.
      Nearly half of ED patients did not obtain an SCr. Many patients did not have
      sequential SCr testing, and a modified definition of AKI was used.

PMID- 28491340
TI  - The Financial Impact of Advanced Kidney Disease on Canada Pension Plan and
      Private Disability Insurance Costs.
AB  - BACKGROUND: Many working-age individuals with advanced chronic kidney disease
      (CKD) are unable to work, or are only able to work at a reduced capacity and/or
      with a reduction in time at work, and receive disability payments, either from
      the Canadian government or from private insurers, but the magnitude of those
      payments is unknown. OBJECTIVE: The objective of this study was to estimate
      Canada Pension Plan Disability Benefit and private disability insurance benefits
      paid to Canadians with advanced kidney failure, and how feasible improvements in
      prevention, identification, and early treatment of CKD and increased use of
      kidney transplantation might mitigate those costs. DESIGN: This study used an
      analytical model combining Canadian data from various sources. SETTING AND
      PATIENTS: This study included all patients with advanced CKD in Canada, including
      those with estimated glomerular filtration rate (eGFR) <30 mL/min/m2 and those on
      dialysis. MEASUREMENTS: We combined disability estimates from a provincial kidney
      care program with the prevalence of advanced CKD and estimated disability
      payments from the Canada Pension Plan and private insurance plans to estimate
      overall disability benefit payments for Canadians with advanced CKD. RESULTS: We
      estimate that Canadians with advanced kidney failure are receiving disability
      benefit payments of at least Can$217 million annually. These estimates are
      sensitive to the proportion of individuals with advanced kidney disease who are
      unable to work, and plausible variation in this estimate could mean patients with
      advanced kidney disease are receiving up to Can$260 million per year. Feasible
      strategies to reduce the proportion of individuals with advanced kidney disease,
      either through prevention, delay or reduction in severity, or increasing the rate
      of transplantation, could result in reductions in the cost of Canada Pension Plan
      and private disability insurance payments by Can$13.8 million per year within 5
      years. LIMITATIONS: This study does not estimate how CKD prevention or increasing
      the rate of kidney transplantation might influence health care cost savings more
      broadly, and does not include the cost to provincial governments for programs
      that provide income for individuals without private insurance and who do not
      qualify for Canada Pension Plan disability payments. CONCLUSIONS: Private
      disability insurance providers and federal government programs incur high costs
      related to individuals with advanced kidney failure, highlighting the
      significance of kidney disease not only to patients, and their families, but also
      to these other important stakeholders. Improvements in care of individuals with
      kidney disease could reduce these costs.

PMID- 28491342
TI  - Hair cortisol and lifetime discrimination: Moderation by subjective social
      status.
AB  - Discrimination has been associated with elevated cortisol as measured in saliva,
      blood, and urine. This study investigated the association between lifetime
      discrimination and hair cortisol concentrations, considered a measure of chronic
      stress. We recruited 180 young adults from diverse backgrounds. Participant
      responses to lifetime discrimination, home stress, and subjective status measures
      were recorded. Lifetime discrimination significantly predicted hair cortisol
      concentrations, supporting past research that discrimination experiences impact
      neuroendocrine systems. To our knowledge, these are the first findings
      associating hair cortisol concentrations with discrimination and supports prior
      evidence positing discrimination as a chronic stressor that serves as a risk
      factor for chronic disease.

PMID- 28491343
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2055102916650093.].

PMID- 28491341
TI  - Validation of the Kidney Failure Risk Equation in Manitoba.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at risk to progress to
      kidney failure. We previously developed the Kidney Failure Risk Equation (KFRE)
      to predict progression to kidney failure in patients referred to nephrologists.
      OBJECTIVE: The objective of this study was to determine the ability of the KFRE
      to discriminate which patients will progress to kidney failure in an unreferred
      population. DESIGN: A retrospective cohort study was conducted using
      administrative databases. SETTING: This study took place in Manitoba, Canada.
      MEASUREMENTS: Age, sex, estimated glomerular filtration rate (eGFR), and urine
      albumin-to-creatinine ratio (ACR) were measured. METHODS: We included patients
      from the Diagnostic Services of Manitoba database with an eGFR <60 mL/min/1.73 m2
      and ACR measured between October 2006 and March 2007. Five-year kidney failure
      risk was predicted using the 4-variable KFRE and compared with treated kidney
      failure events from the Manitoba Renal Program database. Sensitivity and
      specificity for KFRE risk thresholds (3% and 10% over 5 years) were compared with
      eGFR thresholds (30 and 45 mL/min/1.73 m2). RESULTS: Of 1512 included patients,
      151 developed kidney failure over the 5-year follow-up period. The 4-variable
      KFRE showed a superior prognostic discrimination compared with eGFR alone (area
      under the receiver operating characteristic curve [AUROC] values, 0.90 [95%
      confidence interval {CI}: 0.88-0.92] for KFRE vs 0.78 [95% CI: 0.74-0.83] for
      eGFR). At a 3% threshold over 5 years, the KFRE had a sensitivity of 97% and a
      specificity of 62%. At 10% risk, sensitivity was 86%, and specificity was 80%.
      LIMITATIONS: Only 11.7% of stage 3-5 CKD patients had simultaneous ACR
      measurement. The KFRE does not account for other indications for referral such as
      suspected glomerulonephritis, polycystic kidney disease, and recurrent stone
      disease. CONCLUSIONS: The KFRE has been validated in a population with a
      demographic and referral profile heretofore untested and performs well at
      predicting 5-year risk of kidney failure in a population-based sample of
      Manitobans with CKD stages 3 to 5. Thresholds of 3% and 10% over 5 years are
      sensitive, specific, and can be used in clinical decision making. Further testing
      of the 4-variable KFRE and these thresholds in clinical practice should be
      considered.

PMID- 28491344
TI  - Use of sildenafil citrate in a cat with Eisenmenger's syndrome and an atrial
      septal defect.
AB  - A 2-year-old male neutered Siamese cat presenting with weakness and dyspnoea was
      diagnosed with an atrial septal defect and pulmonary hypertension, which resulted
      in right-to-left shunting (Eisenmenger's syndrome). The cat was treated with
      sildenafil (0.25-0.6 mg/kg) for 10 months. There were no apparent treatment
      related adverse effects. Improvement in clinical signs was noted, although
      increasing doses of sildenafil were required. After 10 months the cat
      significantly deteriorated and was euthanased.

PMID- 28491345
TI  - Management of a complete uterine prolapse in a cat.
AB  - A young female cat was presented with a protrusion of the uterus through the
      vulvar lips. The cat had a history of recent parturition, with delivery without
      incident of three kittens 48 h earlier. No fetus was found in the uterus. The
      protruding uterus was amputated and a staged ovariohysterectomy was performed.
      The day after surgery, the queen was healthy with no evidence of vulvar
      discharge. Two months later, the owner reported that the queen was clinically
      normal with no recurrence of clinical signs.

PMID- 28491346
TI  - Metabolic bone disease and central retinal degeneration in a kitten due to
      nutritional inadequacy of an all-meat raw diet.
AB  - A 5-month-old castrated male Sphynx kitten presented with left hindlimb lameness
      shortly after adoption. Prior to adoption, the breeder had fed the kitten an
      exclusively raw chicken diet. Radiographs revealed generalized osteopenia and a
      left tibia-fibula fracture. Ophthalmic examination revealed corneal
      vascularization and opacity in the right eye, and lesions suggestive of feline
      central retinal degeneration in the left eye. The patient's diagnoses included
      metabolic bone disease and feline central retinal degeneration, which can result
      from taurine deficiency. The kitten's nutritional diseases were managed with a
      complete and balanced canned diet designed for kitten growth and with taurine
      supplementation.

PMID- 28491347
TI  - Feline familial pedal eosinophilic dermatosis in two littermates.
AB  - In cats, the most common eosinophilic dermatoses are feline miliary dermatitis
      and eosinophilic granuloma complex. The most commonly identified underlying cause
      is a hypersensitivity reaction. Few cases of familial forms of eosinophilic
      dermatoses are reported in the literature. Two young adult cats from the same
      litter presented 2 years apart with a severe and chronic fluid or tissue
      infiltration of the distal part of several limbs. Lesions started on the forelegs
      and developed on the other limbs. Cytological and histopathological examinations
      showed lesions consistent with an atypical form of feline eosinophilic dermatosis
      associated with secondary bacterial infection. In both cats, antibiotics combined
      with immunosuppressive treatment partially improved the lesions, which continued
      to progress on a waxing and waning course, even in the absence of treatment.
      Allergy work-up did not permit the identification of an underlying allergic
      triggering factor. The severity of the lesions, the unusual presentation and the
      unsatisfactory response to immunosuppressive therapy in two feline littermates
      suggested a genetic form of eosinophilic dermatosis.

PMID- 28491348
TI  - A case of feline systemic reactive angioendotheliomatosis.
AB  - A 3-year-old domestic shorthair cat presented with lethargy and anorexia. A blood
      test showed regenerative anaemia and thrombocytopenia. Thoracic radiographs
      showed a small amount of pleural effusion. The cat did not respond to treatment
      and died on the fifth day. Necropsy revealed moderate pericardial effusion, and
      multifocal coalescing haemorrhages were observed on both atria. Histological
      analysis revealed that the most severe lesions were located on the heart.
      Numerous arterioles supplying the heart were partially to completely filled with
      plump spindle cells that often formed glomerulus-like arrangements within the
      lumen. Similar vascular proliferative lesions were also found in the liver,
      pancreas and kidney. Immunohistochemical analysis showed that these intraluminal
      proliferative spindle cells were positive for anti-von Willebrand factor (vWF).
      Strongly positive antismooth muscle actin staining was observed at the periphery
      of these intraluminal proliferations (comprising arteriolar smooth muscle) and
      certain intraluminal cells (pericytes). The intraluminal thrombi were also
      positive for vWF. Those thrombi were confirmed as platelet thrombi by
      phosphotungstic acid haematoxylin and Masson's trichrome staining. These results
      were consistent with feline systemic reactive angioendotheliomatosis.

PMID- 28491350
TI  - JFMS Open Reports - a new platform for high-quality case reports and
      national/regional data relevant to feline practice.

PMID- 28491349
TI  - Malignant transformation of a duodenal duplication cyst in a cat.
AB  - CASE SUMMARY: A 15-year-old domestic shorthair cat presented for lethargy,
      vomiting and anorexia. Abdominal ultrasound showed a bi-lobed cystic duodenal
      mass. Based on ultrasonographic features, malignant transformation of a duodenal
      duplication cyst was suspected. A resection and anastomosis was performed.
      Histology of the mass was consistent with carcinoma and an intestinal mucosa was
      present along the inner surface of the mass, suggestive of a duplication cyst.
      The patient returned 3 months postsurgery with recurrence of clinical signs.
      Abdominal ultrasound showed a recurrent duodenal mass at the surgery site and
      body wall nodules. Fine-needle aspirates of these lesions showed epithelial
      neoplasia. Owing to the poor prognosis, the owners elected euthanasia. RELEVANCE
      AND NOVEL INFORMATION: Malignant transformation of duplication cysts in cats is
      rare but can be detected on ultrasound. The described ultrasonographic features
      can aid in prioritization of malignant transformation of duplication cysts as a
      differential diagnosis.

PMID- 28491351
TI  - Endophthalmitis due to an intra-ocular linear foreign body in a cat.
AB  - CASE SUMMARY: An unusual case of an intraocular linear foreign body that migrated
      from the oral cavity, causing a severe endophthalmitis, in a cat is described. A
      2-year-old female domestic shorthair cat presented with signs of infection from
      the left eye that had begun 2 weeks previously. Despite having been prescribed
      oral and topical antibiotics, there was a progressive worsening of the clinical
      signs. On ophthalmic examination the cat presented with severe endophthalmitis,
      secondary glaucoma and exposure keratitis of the left eye. Radiography
      demonstrated the presence of an intraocular linear metallic foreign body
      compatible with a sewing needle. During enucleation, when the globe was
      extracted, the sewing needle stayed in the orbit. When the needle was pulled
      away, a piece of thread was also retrieved, which demonstrated that the linear
      foreign body had migrated retrogradely from the oral cavity to the orbit through
      the pterygopalatine fossa. Surgical recovery was uneventful. RELEVANCE AND NOVEL
      INFORMATION: Intraocular foreign bodies may present in a variety of ways, which
      may hinder their clinical detection. The management and prognosis depend on the
      composition and location of the foreign body, as well as the possible presence of
      secondary infection. To the author's knowledge, this is the first time that a
      case of severe endophthalmitis following retrograde intraocular migration of a
      linear foreign body from the oral cavity to the orbit through the pterygopalatine
      fossa in a cat has been reported.

PMID- 28491352
TI  - Fibrosarcoma of the urinary bladder in a cat.
AB  - CASE SUMMARY: A 5-year-old female spayed domestic shorthair cat was presented
      with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non
      painful mass in the urinary bladder was palpated. Abdominal radiographs showed
      thickening and irregular cranial margins of the urinary bladder wall. Abdominal
      ultrasound showed a vascularised mass of mixed echogenicity almost entirely
      occupying the urinary bladder lumen. During explorative laparotomy, the mass
      appeared pedunculated and was totally excised. Histopathology was characterised
      by infiltration of the mucosal, submucosal and muscular layers by proliferated
      atypical mesenchymal cells; immunochemistry confirmed the diagnosis of
      fibrosarcoma. The cat was discharged with normal urination 5 days after surgery.
      The owner declined any imaging follow-up but reported the cat to be free of any
      clinical signs at 16 months after surgery. RELEVANCE AND NOVEL INFORMATION: To
      the best of our knowledge, this is the first case of primary fibrosarcoma of the
      urinary bladder in the cat. Fibrosarcoma should be included in the differential
      diagnosis of urinary bladder neoplasia.

PMID- 28491353
TI  - Multiple acquired portosystemic shunts in a cat secondary to chronic
      diaphragmatic rupture.
AB  - CASE SUMMARY: A cat with a chronic diaphragmatic rupture presented with
      neurological signs, including twitching and focal seizures. Blood ammonia level
      was markedly elevated and therefore neurological signs were thought to be related
      to hepatic encephalopathy. Exploratory laparotomy revealed that the left lateral
      and medial liver lobes were herniated into the thorax and multiple acquired
      portosystemic shunts (MAPSS) were present. The hernia was reduced and the
      diaphragm repaired. Neurological signs gradually resolved following surgery and 1
      year postoperatively the cat was clinically normal, was not on any medication and
      had no evidence of hepatic dysfunction. RELEVANCE AND NOVEL INFORMATION: This is
      the first report of a chronic diaphragmatic rupture leading to MAPSS in a cat.

PMID- 28491354
TI  - Probable vasovagal reaction following cystocentesis in two cats.
AB  - CASE SUMMARY: This case report describes an acute reaction, thought to be vagally
      mediated, in two cats immediately following cystocentesis. Both cats were being
      evaluated for feline idiopathic cystitis and developed bradycardia,
      hypersalivation, urination and weakness after a blind cystocentesis. Both cats
      recovered uneventfully with supportive care. RELEVANCE AND NOVEL INFORMATION: A
      vagally mediated response may occur in cats after cystocentesis, which is a
      common procedure performed by veterinary professionals in cats. This response may
      be very profound and dramatic. Affected cats will likely make an uneventful
      recovery. This vagally mediated response to cystocentesis, though reported by
      word of mouth among veterinarians, has not been described in the literature. This
      is the first documentation of its occurrence in cats.

PMID- 28491356
TI  - Rapid vascular uptake of contrast during a retrograde urethro-cystogram in a cat
      with chronic lower urinary tract disease.
AB  - CASE SUMMARY: A 9-year male neutered domestic longhair cat was referred to our
      hospital for investigation of recurrent urinary tract obstruction. The clinical
      signs had started 12 months earlier and the cat had been catheterised on multiple
      occasions. Clinical examination and abdominal ultrasound of the abdomen was
      unremarkable but examination of the penis revealed it to be prolapsed and
      extremely erythematous and friable. A retrograde contrast urethrocystogram was
      performed, showing extravasation of the contrast medium and establishing the
      presence of partial leakage or a tear of the urethra. In subsequent radiographs,
      the contrast was seen being rapidly absorbed into the pelvic and systemic
      vasculature via the penile veins, internal and external pudendal veins, internal
      and external iliac veins, and, ultimately, the caudal vena cava. Later, the
      contrast medium was seen within the renal pelves. Retrograde urethrocystography
      revealed stenosis and irregularities of the caudal urethral mucosa consistent
      with strictures. A routine perineal urethrostomy was performed and the cat
      recovered well. CONCLUSIONS AND RELEVANCE: Rapid vascular absorption of
      extravasated contrast medium has not been reported before. In this case, the
      increased blood supply to the distal urethra and penis is likely secondary to
      (chronic) inflammation, as demonstrated by the urethral strictures and the
      friable, oedematous nature of the penis. Whether the inflammation was caused by
      chronic obstruction or repeated iatrogenic trauma, or a combination of these
      factors, will remain debatable. Nonetheless, this case demonstrates that when a
      retrograde contrast urethrocystogram is considered, it is imperative that a
      contrast medium (or other intraurethral medication such as local anaesthesia) is
      chosen that is safe for intravascular use. Equally, an absolute aseptic technique
      is essential considering the potential for contaminants to be absorbed quite
      rapidly into the systemic circulation. Multiple catheterisations should be
      avoided when there is chronic inflammation, and alternative options should be
      considered when chronic disease is suspected.

PMID- 28491355
TI  - Otogenic meningoencephalomyelitis due to Cryptococcus gattii (VGII) infection in
      a cat from Western Australia.
AB  - CASE SUMMARY: A 7-year-old spayed domestic longhair cat from Perth, Western
      Australia, presented with left-sided head tilt, dysphonia, head shaking,
      inappetence and weight loss. A polypoid lesion had previously been removed from
      the external ear canal. Otitis media with extension into the external ear canal
      was suspected and investigated using video-otoscopy and computed tomography
      examination. Invasive disease with extension from the middle ear to the base of
      the skull, and intracranial extension into the caudal fossa and cranial cervical
      vertebral canal was detected. Cytology of external ear canal exudate showed
      capsulated budding yeasts and Cryptococcus gattii VGII was cultured. Treatment
      with amphotericin B infusions and oral fluconazole was prescribed, with
      nutritional support via oesophagostomy tube. The cat clinically recovered 12
      months after treatment commenced. RELEVANCE AND NOVEL INFORMATION: This case
      report describes the successful medical treatment of otogenic
      meningoencephalomyelitis due to C gattii (VGII) infection in a cat.

PMID- 28491357
TI  - Marked cytoreduction of a lymphocyte-rich mediastinal thymoma with neoadjuvant
      chemotherapy in a cat.
AB  - CASE SUMMARY: A 15-year-old neutered female domestic shorthair cat presented with
      lethargy and acute-onset dyspnoea. Thoracic computed tomography (CT) revealed a
      large, cranial mediastinal mass with an estimated volume of 180.7 cm3.
      Chemotherapy consisting of dexamethasone followed by L-asparaginase,
      prednisolone, vincristine and doxorubicin was commenced owing to the severity of
      disease and initial possibility of lymphoma. A diagnosis of lymphocyte-rich
      thymoma was made based upon histological examination, positive pancytokeratin
      staining, variable lymphocyte CD3 expression and T cell receptor gamma
      polyclonality. Thoracic CT performed 35 days after the commencement of
      chemotherapy showed a marked reduction in the size of the mass, with an estimated
      volume of 9.4 cm3. A median sternotomy and thymectomy were performed. No clinical
      signs have recurred 34 months after surgery. CONCLUSIONS AND RELEVANCE: The
      response to chemotherapy in this case was unusual, and is likely associated with
      the high non-neoplastic lymphoid component of the mass. The case demonstrates
      that preoperative chemotherapy can be used to reduce thymoma volume prior to
      surgery, potentially decreasing anaesthetic risk.

PMID- 28491358
TI  - Evaluation of thromboelastography in two factor XII-deficient cats.
AB  - CASE SUMMARY: The current report describes thromboelastography (TEG) findings in
      two cats with factor XII (FXII) deficiency. The first cat was diagnosed with
      bilateral perinephric pseudocysts; hemostatic testing was performed prior to
      performing renal aspirates. The second cat was healthy; hemostatic testing was
      performed prior to inclusion into a research project. Both cats had markedly
      prolonged partial thromboplastin times and hypocoagulable TEG tracings when
      samples were activated with kaolin. However, when tissue factor (TF) was used to
      activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The
      cats each had a subnormal FXII level. RELEVANCE AND NOVEL INFORMATION: TEG is
      becoming widely used to investigate hemostasis in veterinary patients, and TEG
      results in cats with FXII deficiency have not been previously reported. FXII
      deficiency is the most common hereditary hemostatic defect in cats. While FXII
      deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked
      prolongation in activated partial thromboplastin and activated clotting times,
      and cannot be differentiated from true hemorrhagic diatheses without measuring
      individual factor activity. With the increased use of TEG to evaluate hemostasis
      in veterinary patients, it is important to recognize the effects of FXII
      deficiency on this testing modality. The finding of a hypocoagulable kaolin
      activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples
      should prompt clinicians to consider ruling out FXII deficiency.

PMID- 28491359
TI  - Praziquantel treatment for Platynosomum species infection of a domestic cat on St
      Kitts, West Indies.
AB  - CASE SUMMARY: A 1-year-old, female spayed, domestic shorthair, indoor cat on the
      island of St Kitts was diagnosed with platynosomiasis, infection with a feline
      specific liver fluke, and treated with praziquantel at the marketed dose for
      tapeworms (5 mg/kg; actual calculated dose 5.75 mg/kg). Serial fecal analyses
      showed that egg counts decreased to zero within 10 days of treatment but re
      emerged at day 17 and persisted at low levels until a second treatment was
      administered on day 78. After the second treatment, all fecal samples (n = 15)
      from day 85 to day 350 post-initial treatment were negative for Platynosomum ova.
      RELEVANCE AND NOVEL INFORMATION: Treatment of platynosomiasis is poorly
      documented; no drugs are labeled for use against Platynosomum and the efficacy of
      suggested treatments is unknown. Using 5.75 mg/kg once, a dose that is
      significantly lower than published recommended doses for platynosomiasis, egg
      counts initially disappeared but re-emerged and persisted at low levels until a
      second treatment was administered. We hypothesize that immature forms may not
      have been killed and subsequently matured to produce eggs, or that the one-time
      dose may not have been completely effective at eliminating all adult flukes.
      However, administering praziquantel at 5.75 mg/kg twice, several weeks apart,
      appeared to be effective in treating this cat with platynosomiasis, as evidenced
      by monitoring of fecal egg counts over the course of 350 days.

PMID- 28491360
TI  - Esophageal stricture caused by rib osteoma in a cat: case report.
AB  - CASE SUMMARY: A 6-year-old male domestic shorthair cat presented with frequent
      food regurgitation and dysphagia. Plain thoracic radiographs revealed a calcified
      mass overlying the topography of the mediastinum, as well as dilation of the
      cervical portion of the esophagus due to an accumulation of food. Endoscopic
      examination showed a severe extraluminal esophageal stricture at the mediastinum
      entrance. Surgery and a gastric tube were declined by the cat's owner, with
      palliative support preferred. However, 1 year later, the cat presented with
      severe cachexia, dysphagia, salivation, dehydration and inspiratory dyspnea.
      Thoracic computed tomography was performed to evaluate the possibility of
      surgical resection. A mass of bone density originating in the second left rib was
      observed. The mass did not appear to have invaded adjacent structures but marked
      compression of the mediastinal structures was observed. Surgical resection was
      performed and a prosthetic mesh was used to reconstruct the thoracic wall.
      Transient Horner's syndrome developed in the left eye postoperatively, and was
      resolved within 4 weeks. Histopathology revealed a benign osteoma. Thirty-two
      months after surgery, the cat was well and free of disease. RELEVANCE AND NOVEL
      INFORMATION: Rib tumors should be included in a differential diagnosis in cats
      with extraluminal esophageal stricture. CT should be performed for treatment
      planning. Surgical treatment was curative in this case.

PMID- 28491361
TI  - Orbital actinomycotic mycetoma caused by Streptomyces cinnamoneus.
AB  - CASE SUMMARY: An 18-month-old male neutered Ragdoll cat presented with an 8 week
      history of progressive unilateral right-sided mucopurulent nasal discharge and
      exophthalmos. Magnetic resonance imaging revealed a heterogeneous right
      retrobulbar mass and bilateral nasal cavity disease. Filamentous structures seen
      on cytology of retrobulbar and nasal biopsies were mistakenly identified as
      filamentous fungal hyphae. Subsequent investigations revealed that the cat had a
      retrobulbar actinomycotic mycetoma with invasion of the globe. The aetiological
      agent was identified on 16S recombinant DNA sequencing as Streptomyces
      cinnamoneus. After exenteration and chronic antimicrobial therapy the cat was
      alive and well 3 years after presentation. RELEVANCE AND NOVEL INFORMATION: This
      is the first report of a pathogenic role of S cinnamoneus in a cat. Orbital
      actinomycotic mycetomas in cats can resemble mycotic granulomas.

PMID- 28491362
TI  - Successful conservative management of suspected Fournier's gangrene in cats:
      three cases.
AB  - CASE SERIES SUMMARY: Three cats with suspected Fournier's gangrene had an acute
      onset of clinical signs and bloodwork changes consistent with sepsis. All cases
      had similar progression of wounds that were managed without aggressive surgical
      debridement, which is the currently accepted treatment of choice. All cats
      survived and have maintained an excellent long-term quality of life. RELEVANCE
      AND NOVEL INFORMATION: Fournier's gangrene is a potentially fatal disease, with
      few cases reported in the veterinary literature. This retrospective case series
      describes the only known reports of survival from suspected Fournier's gangrene
      cats, none of which required aggressive surgical debridement.

PMID- 28491363
TI  - Neuroendocrine pituitary macroadenoma of a cat presenting with primary adipsia
      and hypernatraemia.
AB  - CASE SUMMARY: A male neutered Ragdoll cat aged 11 years and 9 months presented
      with a 6 month history of weight loss and a 1 month history of lethargy and
      adipsia. A thorough clinical investigation confirmed a diagnosis of primary
      adipsia and hypernatraemia secondary to a non-secretory neuroendocrine pituitary
      macroadenoma. RELEVANCE AND NOVEL INFORMATION: Primary adipsia is a very rare
      clinical entity. This report is the first to describe primary adipsia secondary
      to a non-secretory pituitary macroadenoma in the cat. The veterinary literature
      available in this field is very limited and this report adds a new differential
      diagnosis for cats presenting with primary hypodipsia.

PMID- 28491364
TI  - Traumatic spinal cord injury caused by suspected hyperflexion of the atlantoaxial
      joint in a 10-year-old cat.
AB  - CASE SUMMARY: A 10-year-old cat presented 5 days after a traumatic event with
      acute recumbency followed by some clinical improvement. The neuroanatomical
      localisation was the C1-C5 spinal cord segments. Initial survey radiographs,
      including lateral flexed views, showed no convincing abnormalities. Magnetic
      resonance imaging (MRI) revealed a marked focal intramedullary lesion at the
      level of the dens and suspected oedema extending over C2-C3 vertebrae, suggesting
      early syrinx formation. The cat made an initial excellent recovery on restricted
      exercise without medical treatment. The MRI changes largely resolved on follow-up
      MRI 4 weeks later yet recurred following a relapse 4 months later. At this stage,
      a post-traumatic syrinx had developed. Moreover, the suspected atlantoaxial
      instability was finally diagnosed on radiography with fully flexed lateral views.
      A hyperflexion injury causing tearing of the atlantoaxial ligaments was
      considered most likely given the lack of malformations or fractures. The cat made
      a full recovery on conservative management. RELEVANCE AND NOVEL INFORMATION: This
      is the first report of sequential MRI findings in a cat with atlantoaxial
      instability. Moreover, post-traumatic syringomyelia formation following
      atlantoaxial injury has not been reported. Sequential MRI aids in the diagnosis
      of hyperflexion injury if survey radiographs fail to identify atlantoaxial
      instability.

PMID- 28491365
TI  - Ascending haemorrhagic myelomalacia associated with systemic hypertension in a
      hyperthyroid cat.
AB  - CASE SUMMARY: An 8-year-old domestic shorthair neutered male cat was presented
      with acute onset of paraplegia, absent nociception on the pelvic limbs, tail and
      perianal area, and a previous history of uncontrolled hyperthyroidism (even after
      thyroidectomy) and chronic hypertension. The magnetic resonance findings
      (heterogeneous intramedullary ill-defined area, isointense on T1-weighted and
      hyperintense on short tau inversion recovery and T2-weighted scans between T12
      and L5 spinal cord segments) were consistent with ascending haemorrhagic
      myelomalacia, which was confirmed by histopathology. It also revealed
      myelomalacia associated with diffuse arteriolar hyalinosis, similar to the
      reports found with hypertensive encephalopathy. RELEVANCE AND NOVEL INFORMATION:
      Myelomalacia should be considered as a possible outcome in cats with
      hypertension. Considering that hypertension is a common consequence of
      hyperthyroidism, emphasis should be given to blood pressure monitoring,
      especially after treatment of this condition. We describe the histopathological
      changes occurring in the spinal cord associated with a state of hypertension.

PMID- 28491366
TI  - Migration of a sewing needle foreign body into the brainstem of a cat.
AB  - CASE SUMMARY: A 1-year-old, female spayed domestic shorthair cat with a 6 week
      history of upper respiratory signs and a progressive reluctance to move, which
      culminated in a right-sided hemiparesis, was found to have a sewing needle
      foreign body lodged in the brainstem. Surgical extraction of the needle was
      successful and the cat's neurological deficits resolved over the days to weeks
      following its removal. RELEVANCE AND NOVEL INFORMATION: This case report
      describes, to our knowledge, the first reported incidence and management of an
      ingested sewing needle migrating into the central nervous system of a cat.

PMID- 28491367
TI  - Blepharitis due to Cryptococcus neoformans in a cat from northern Portugal.
AB  - Case summary We report a clinical case of blepharitis due to Cryptococcus
      neoformans yeasts in a 2-year-old stray cat from northern Portugal (Vila Real)
      without concurrent naso-ocular signs. Ophthalmological examination revealed
      mucopurulent discharge from an open wound in the right upper and lower lids. Slit
      lamp biomicroscopy showed a normal anterior segment, and intraocular pressure was
      within the normal reference interval. No fundoscopic alterations were detected in
      either eye by direct and indirect ophthalmoscopic examination. Cytological
      examination of an appositional smear showed numerous polymorphic neutrophils and
      macrophages, together with spherical yeast cells compatible with Cryptococcus
      species. Molecular analysis by means of PCR and restriction fragment length
      polymorphism identified C neoformans genotype VNI. The cat was treated with
      itraconazole, and amoxicillin and clavulanic acid, combined with a commercial ear
      ointment and an imidacloprid/moxidectin spot-on application for bilateral
      parasitic otitis caused by Otodectes cynotis. One month after treatment, the
      clinical signs were completely resolved. Localised cutaneous lesions, as in the
      present case, probably result from contamination of cat-scratch injuries with
      viable encapsulated yeasts. Relevance and novel information This is, to the best
      of our knowledge, the first clinical report of feline blepharitis due to C
      neoformans without concurrent naso-ocular signs. The current findings, together
      with those from recent reports of the infection in domestic animals, should alert
      the veterinary community both in Portugal and in Europe to this underdiagnosed
      disease.

PMID- 28491368
TI  - First report of Cylicospirura felineus in a feral domestic shorthair cat in North
      America.
AB  - CASE SUMMARY: A feral domestic shorthair cat was euthanized owing to acute onset
      and progression of neurological signs attributed to ethylene glycol toxicity. At
      post-mortem examination two nodules were identified within the fundus of the
      stomach. Examination of the gastric nodules revealed an intact mucosal surface,
      each with multiple red slender nematodes extending through an individual central
      pore. Histopathological evaluation of the nodules highlighted unique reactive
      fibroplasia, mimicking feline gastrointestinal eosinophilic sclerosing
      fibroplasia (FGESF), encasing numerous nematodes with females possessing gravid
      uteri containing abundant larvated eggs. The latter findings were highly
      suggestive of the Cylicospirura genus, further supported by an en face evaluation
      of the buccal cavity, highlighting a distinctive trifid tooth appearance.
      Together, these findings are consistent with Cylicospirura felineus. PCR for the
      COX-1 gene was unsuccessful on formalin-fixed specimens, attributed to nucleic
      acid and protein crosslinking. RELEVANCE AND NOVEL INFORMATION: This represents
      the first documented case of Cylicospirura species in a feral domestic shorthair
      cat in North America. This particular cat lived in the highly urban environment
      of New Orleans, Louisiana. Identification of this case demonstrates the potential
      for feral cats to serve as reservoir hosts and ultimately support transmission of
      Cylicospirura species into domesticated cat populations. Gastric
      cylicospiruriasis may present clinically as a firm abdominal mass, potentially
      with a history of chronic vomiting. The latter emphasizes the importance of
      differentiating this condition from a neoplastic process such as alimentary
      lymphoma and adenocarcinoma. Histologically, the unique thick anastomosing
      collagenous cords encasing nematodes represent a stereotypical response observed
      in a broad array of gastrointestinal inflammation in felines, including
      intralesional bacteria, fungal hyphae, foreign bodies and, in this case, gastric
      nematodes that closely resemble FGESF. Additionally, these unique histological
      lesions have previously been misinterpreted as neoplastic conditions, including
      sclerosing mast cell tumor and extraosseous osteosarcoma.

PMID- 28491369
TI  - Superficial temporal myofascial flap application in temporomandibular joint
      arthroplasty in a cat.
AB  - CASE SUMMARY: A 2-year-old, intact female domestic longhair cat was referred for
      surgical treatment after diagnosis of closed jaw locking secondarily to right
      temporomandibular joint ankylosis and left pseudoankylosis. The animal underwent
      successful surgical management with bilateral excision arthroplasty followed by
      interposition of a temporal superficial myofascial flap. Immediately after
      surgery, the full range of lower jaw movement was achieved and normal occlusion
      was maintained. Ankylosis did not recur in the 1 year postoperative follow-up
      period. RELEVANCE AND NOVEL INFORMATION: A temporal myofascial flap could be
      considered as interposition material after temporomandibular joint arthroplasty
      to avoid postoperative re-ankylosis and mandibular drift. The main advantages of
      this flap are its autogenous origin, and the ability to maintain separation
      between the two bones, preserve mobility and disrupt new bone formation.

PMID- 28491370
TI  - Primary angiocentric/angioinvasive T-cell lymphoma of the tympanic bulla in a
      feline leukaemia virus-positive cat.
AB  - Case summary A 5-year-old neutered female feline leukaemia virus (FeLV)-positive
      domestic shorthair cat with a 5 month history of otitis media was referred for
      head tilt, stertor and dyspnoea. Computed tomography scan revealed soft tissue
      opacities inside the right tympanic bulla, with bone remodelling, and concurrent
      nasopharyngeal and intracranial invasion. Endoscopically guided bioptic samples
      were collected from the nasopharynx and middle ear. Histology revealed dense
      sheets of round, large, neoplastic cells, often surrounding or invading vascular
      walls. Neoplastic cells expressed CD3, FeLV p27 and gp70 antigens. A middle ear
      angiocentric/angioinvasive T-cell lymphoma was diagnosed. After improvement of
      clinical conditions following radiation therapy, the cat died unexpectedly. At
      necropsy, hepatic and splenic spread was detected. Relevance and novel
      information Primary middle ear tumours are rare and their diagnosis is often
      delayed as clinical signs mimic more common otological conditions. Multiple
      bioptic specimens are pivotal for a definitive diagnosis. The young age of the
      cat, serology and immunohistochemistry revealed a possible transforming role of
      FeLV.

PMID- 28491371
TI  - Selective fatty replacement of the exocrine pancreas in a domestic shorthair cat:
      histopathological findings with long-term outcome.
AB  - The clinical, histopathological findings and eventual outcome of a cat with
      marked and selective fatty replacement of the exocrine pancreas are described in
      this case report. A 9-year-old female neutered domestic shorthair cat presenting
      with polyphagia, weight loss and intermittent vomiting was diagnosed on
      histopathology with severe exocrine pancreatic atrophy, with relative sparing of
      the endocrine pancreas and replacement of the acinar cells by mature adipose
      tissue. This case report discusses the histological findings in this case and the
      eventual outcome, as well as the potential underlying causes of this histological
      change.

PMID- 28491372
TI  - Hypertrophic osteopathy in a cat with a concurrent injection-site sarcoma.
AB  - Case summary An 11-year old neutered female domestic shorthair cat presented for
      investigation of a large, partially ulcerated skin mass in the area of the left
      scapula. The cat had been vaccinated 6 weeks previously in the same area.
      Haematology showed a marked neutrophilia and monocytosis. Tru-cut biopsies were
      taken and histopathology was consistent with a high-grade soft tissue sarcoma.
      Thoracic radiographs and abdominal ultrasound revealed no abnormalities. Moderate
      mixed (palisading, brush border and smooth) periosteal reaction was seen on the
      diaphysis of long bones at the time of the radiographic examination. Magnetic
      resonance imaging of the mass showed infiltration within deeper tissues and the
      owners elected euthanasia. Post-mortem examination confirmed the presence of
      hypertrophic osteopathy with a concurrent injection-site sarcoma. No evidence of
      intra-thoracic or intra-abdominal disease was found. Relevance and novel
      information To our knowledge, this is the first report where hypertrophic
      osteopathy has been described in a cat with a soft tissue sarcoma, most likely an
      injection-site sarcoma.

PMID- 28491373
TI  - First case of feline leishmaniosis caused by Leishmania infantum genotype E in a
      cat with a concurrent nasal squamous cell carcinoma.
AB  - CASE SUMMARY: This is the first clinical report of feline viscerocutaneous
      leishmaniosis caused by Leishmania infantum genotype E associated with an
      invasive squamous cell carcinoma (SCC) in a domestic cat from Portugal.
      Initially, the cat presented a single cutaneous lesion in the right nostril. A
      fine-needle aspiration was performed and Leishmania amastigotes were observed
      without the presence of cells compatible with neoplasia. Systemic treatment with
      allopurinol was started. One year later, the cat presented a crateriform non
      encapsulated and badly delineated mass in the nasal planum, with naso-oral
      fistulation and nasal destruction. Histologically, the skin mass consisted on an
      ulcerative plaque-like lesion with a nasal SCC. Leishmania infantum MON-1
      parasites were detected by histopathology, culture and PCR of the skin mass,
      submandibular and popliteal lymph nodes, liver and spleen. Restriction enzyme
      analysis revealed genotype E, previously identified in humans and dogs living in
      the same region. RELEVANCE AND NOVEL INFORMATION: This is, to the best of our
      knowledge, the first clinical report of feline viscerocutaneous leishmaniosis
      caused by L infantum genotype E. The detection and isolation of parasites from a
      cat that are genetically identical to the ones obtained from humans and dogs with
      visceral leishmaniosis highlights the need to clarify whether cats play a role in
      the epidemiology of this parasitic zoonosis. From a clinical point of view, this
      case reinforces the importance of including leishmaniosis in the differential
      diagnoses of feline pathology, especially in cats with cutaneous lesions.

PMID- 28491374
TI  - Supratentorial arachnoid cyst management by cystoperitoneal shunt in a 1-year-old
      European cat.
AB  - Arachnoid cysts are defined as an accumulation of fluid within the arachnoid
      membrane. Feline intracranial arachnoid cysts are seldom reported, with only
      three cases in the veterinary literature. A 1-year-old male neutered European cat
      with a 24 h history of seizures was presented to the small animal neurology
      department at Vetagro Sup, Lyon. Magnetic resonance imaging (MRI) revealed a
      large intracranial arachnoid cyst ventral to the brain in the left temporal area.
      Cystoperitoneal shunt placement resulted in complete resolution of the cyst
      without recurrence (follow-up MRIs 3 weeks and 21 months after surgery).
      Anticonvulsant treatment (phenobarbital 2.5 mg/kg q12h) was initiated at
      presentation and gradually stopped after 17 months. Seizures recurred 4 months
      after ending treatment, and seizure therapy was therefore restarted at the
      initial dose. We report a case of an intracranial arachnoid cyst in an unusual
      location not previously described. A cystoperitoneal shunt resolved the cyst
      without complications. Maintenance anticonvulsant treatment was required to
      control symptomatic epilepsy.

PMID- 28491375
TI  - Incidental echocardiographic findings of a quadricuspid aortic valve associated
      with aortic regurgitation in a cat.
AB  - CASE SUMMARY: A 10-month-old male domestic shorthair cat was brought to
      Kitanomori Animal Hospital for routine castration. Preoperative thoracic
      radiography revealed a mildly enlarged heart silhouette, and transthoracic
      echocardiography (ECHO) suggested a quadricuspid aortic valve associated with
      central aortic regurgitation (regurgitant fraction 31%). After sedation with
      intramuscular medetomidine and midazolam for castration, heart rate decreased
      from 193 to 76 beats per minute. ECHO under sedation revealed two equally small
      and two equally large aortic valve cusps, suggesting a type C quadricuspid aortic
      valve. The findings were confirmed by real-time three-dimensional ECHO. RELEVANCE
      AND NOVEL INFORMATION: This case reveals the echocardiographic features of a
      feline quadricuspid aortic valve and shows that transthoracic ECHO is useful to
      examine aortic valve morphology in cats. It also suggests that echocardiographic
      screening may be beneficial for detecting congenital cardiac anomalies in
      apparently healthy cats.

PMID- 28491376
TI  - Digital flexor tendon contracture treated by tenectomy: different clinical
      presentations in three cats.
AB  - CASE SERIES SUMMARY: Three cats, Siamese or Siamese cross, were presented with a
      chronic thoracic limb weightbearing lameness. Previous anti-inflammatory
      administrations were unable to improve lameness consistently in the three cats.
      Two of the three cats had undergone onychectomy several years before
      presentation. A permanent flexion of the proximal interphalangeal joint of one or
      more digits, associated with a difficult and painful extension of the proximal
      interphalangeal joint, was noticed during orthopedic examination. A digital
      flexor tendon contracture was suspected and confirmed with radiographic
      examination. Surgical exploration was then performed. For all cats, treatment
      consisted of a tenectomy or tenotomy of the superficial and deep digital flexor
      tendons in order to release the contracture. The three cats responded well to the
      surgical treatment and became sound around 2-4 weeks after surgery. RELEVANCE AND
      NOVEL INFORMATION: Digital flexor tendon contracture is rarely reported as a
      cause of lameness in cats. It should be considered in a differential diagnosis of
      feline lameness whenever onychectomy has been performed in the past. The precise
      etiology that explains this tendon contracture is unknown, but trauma or breed
      predisposition could represent potential causes.

PMID- 28491377
TI  - Cryptococcal nasopharyngeal polypoid mass in a cat.
AB  - CASE SUMMARY: An indoor 9-year-old castrated male domestic cat was referred with
      a 4 month history of increased upper airway noise. Computed tomography revealed a
      nasopharyngeal polypoid mass, which was removed endoscopically with basket
      forceps. Histopathology was compatible with a polypoid granulomatous pharyngitis
      with Cryptococcus-like organisms. This was supported by a positive serum latex
      cryptococcal antigen agglutination test (LCAT). Minimal inflammation of the nasal
      tissue was noted on histopathology, with no evidence of fungus. Following
      endoscopic removal of the mass, the patient was treated with systemic antifungal
      medication (itraconazole). One year after diagnosis, the LCAT titer was negative
      and the cat remained free of clinical signs. RELEVANCE AND NOVEL INFORMATION:
      This case report emphasizes the importance of considering Cryptococcus species as
      a potential etiology in cats presented with signs of nasopharyngeal obstruction
      with an isolated nasopharyngeal polypoid mass, even if kept indoors.

PMID- 28491378
TI  - Spontaneous thoracolumbar hematomyelia secondary to hemophilia B in a cat.
AB  - CASE SUMMARY: A 10-year-old neutered male domestic shorthair cat presented for
      evaluation of acute onset of paraplegia with loss of nociception and
      thoracolumbar spine hyperesthesia and no history of trauma. Activated partial
      thromboplastin time (aPTT) was markedly prolonged, and specific coagulation
      factor testing revealed a factor IX level of 4% of normal activity, confirming
      the presence of mild hemophilia B. Prior abnormal bleeding had occurred at the
      time of castration as a kitten, as well as with laceration to a toe. Advanced
      imaging, including computed tomography (CT) and magnetic resonance imaging (MRI)
      of the thoracolumbar spine, confirmed the presence of multifocal intradural and
      intramedullary spinal cord hemorrhage through demonstration of focal ring
      enhancement on CT and multifocal areas of signal void on gradient echo T2* images
      on MRI. Despite factor IX supplementation through the use of fresh frozen plasma
      transfusions and normalization of the aPTT time, the cat's neurological status
      did not improve. Owing to repeated urinary tract infections, with increasing
      resistance to antibiotic therapy, the cat was ultimately euthanized. Post-mortem
      examination showed no evidence of another underlying primary pathology for the
      hematomyelia. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this case
      demonstrates the first reported occurrence of spontaneous hematomyelia secondary
      to hemophilia B in a cat.

PMID- 28491379
TI  - Nasofacial infection in a cat due to a novel bacterium in Neisseriaceae.
AB  - CASE SUMMARY: A 2-year-old female spayed domestic shorthair cat was presented for
      a progressive subcutaneous nasofacial swelling. Histology of biopsy tissue
      revealed pyogranulomatous inflammation and large numbers of gram-negative
      capsulated bacterial coccobacilli within macrophages. The isolate was fastidious
      and grew after 6 days under microaerophilic conditions in a candle jar. The
      molecular identity of the isolate, from comparative sequence analysis of the 16s
      rRNA gene, is an as yet to be classified bacterial species within a novel genus
      of Neisseria. Infection resolved after 7 months of antimicrobial therapy with
      doxycycline and trimethoprim sulfamethoxazole. There has been no further
      recurrence of clinical signs in a 3 year follow-up period. RELEVANCE AND NOVEL
      INFORMATION: Cats are susceptible to nasofacial infections as a result of
      traumatic inoculation of environmental bacteria, fungi and protozoa. We report a
      novel pathogen in the Neisseriaceae family, identified by 16 sRNA comparative
      sequence analysis, as a cause of nasofacial infection in a cat, and its
      subsequent successful treatment with combination antimicrobial therapy.

PMID- 28491380
TI  - A survey of feline leukaemia virus antigenaemia among cats in eastern Austria: a
      retrospective analysis of serum samples routinely tested between 1996 and 2011.
AB  - OBJECTIVES: The aim of this retrospective analysis was to determine the
      seroprevalence of feline leukaemia virus (FeLV) antigenaemia among owned cats in
      Vienna and the surrounding area. METHODS: Samples were tested between 1996 and
      2011 by the Department of Clinical Virology at the University of Veterinary
      Medicine, Vienna, Austria. All samples were sent to the university as part of
      routine diagnostic procedures, either to determine infection in clinically
      symptomatic individuals or to rule out infection prior to vaccination. To allow
      for statistical comparison, samples analysed between 2008 and 2011 were pooled
      into one population (n = 444) and evaluated against samples tested in 1996 (n =
      840). Furthermore, analyses of subgroups were undertaken to determine the effect
      of sex and age on the prevalence of FeLV antigenaemia. RESULTS: With respect to
      the samples tested at the University of Veterinary Medicine in Vienna, it was
      determined that the level of FeLV antigenaemia in eastern Austria between 1996
      and 2011 was 5.6%. The proportion of FeLV antigenaemic cats was highly variable
      and has not fallen significantly over this period, despite advances in
      vaccination, and the education of pet owners and animal welfare charities.
      CONCLUSIONS AND RELEVANCE: This study confirms the importance of continued and
      regular vaccination against FeLV among Austrian cats, particularly those allowed
      access to the outdoors. Within the remit of this retrospective study, it was not
      possible to follow-up results of repeat testing or of other assays (PCR) of
      individual cats. As a result of this, no conclusions can be drawn as to the
      possibility of transient antigenaemic cats or false-positive enzyme-linked
      immunosorbent assay results.

PMID- 28491381
TI  - A case of spongiform polioencephalomyelopathy in a cat with a history of
      behavioural problems.
AB  - A 7-month-old, entire female, domestic shorthair cat was referred to our
      behavioural service owing to soiling in the house and a play-related problem. The
      owners' complaints were that the cat had never used the litter tray, and it did
      not know how to play. After reviewing the behavioural history, a problem of
      substrate preferences acquisition was suspected with regard to the elimination
      problem. During the consultation, the physical examination was unremarkable, but
      the neurological examination revealed a moderate and hypermetric ataxic gait, and
      a bilateral lack of menace response. Some degree of visual impairment was
      suspected. The problem was located in the central nervous system (CNS);
      specifically, an intracranial and multifocal problem was diagnosed. After a
      complete work-up (complete ophthalmological examination, complete blood count and
      a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia
      virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance
      imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen
      test), a degenerative CNS problem was suspected. No treatment was prescribed for
      the neurological problem. Regarding the problem of soiling in the house, reward
      based training with a clicker was used, and the cat partially improved in a few
      weeks. Three months later, the cat was referred to the neurology service in
      status epilepticus. A symptomatic treatment was prescribed, with a mild response.
      After 2 years of treatment and a progressive worsening, the cat was euthanased.
      Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion
      aetiology a PrPsc inmunohistochemistry assay was performed, and the results were
      negative. Congenital spongiform polioencephalomyelopathy (CSP) was diagnosed. We
      strongly suggest that the cat's behavioural clinical signs were caused by the
      CSP, causing learning impairment. To the best of our knowledge, this would be the
      first case in which a congenital degenerative disease affected a cat's capability
      to learn, leading to behavioural signs as the main complaint of the owners, even
      before neurological signs are detected by the owners.

PMID- 28491382
TI  - Bartonella henselae as a cause of acute-onset febrile illness in cats.
AB  - CASE SERIES SUMMARY: At different time points spanning 6 months, three adopted
      feral flea-infested cats, residing in the household of a veterinary technician,
      became acutely anorexic, lethargic and febrile. Enrichment blood culture/PCR
      using Bartonella alpha Proteobacteria growth medium (BAPGM) confirmed initial
      infection with the same Bartonella henselae genotype in all three cases. With the
      exception of anemia and neutropenia, complete blood counts, serum biochemical
      profiles and urinalysis results were within reference intervals. Also, tests for
      feline leukemia virus, feline immunodeficiency virus, Toxoplasma gondii and
      feline coronavirus antibodies were negative. Serial daily temperature monitoring
      in one case confirmed a cyclic, relapsing febrile temperature pattern during 1
      month, with resolution during and after treatment with azithromycin. Bartonella
      henselae Western immunoblot (WB) results did not consistently correlate with
      BAPGM enrichment blood culture/PCR results or B henselae indirect fluorescent
      antibody (IFA) titers, and WB titration results were not informative for
      establishing antibiotic treatment failure. During the respective follow-up
      periods, no illnesses or additional febrile episodes were reported, despite
      repeat documentation of B henselae bacteremia in two cats available for follow-up
      (one with the same genotype and the other with a different B henselae genotype);
      one cat was, unfortunately, killed by dogs before follow-up testing. RELEVANCE
      AND NOVEL INFORMATION: We conclude that microbiological diagnosis and treatment
      of B henselae infection in cats can be challenging, that antibody titration
      results and resolution of clinical abnormalities may not correlate with a
      therapeutic cure, and that fever and potentially neutropenia should be
      differential diagnostic considerations for young cats with suspected
      bartonellosis.

PMID- 28491383
TI  - Repair of a sliding (type I) hiatal hernia in a cat via herniorrhaphy,
      esophagoplasty and floppy Nissen fundoplication.
AB  - CASE SUMMARY: A 10-month-old domestic shorthair cat was evaluated for severe
      esophagitis and protracted vomiting and regurgitation secondary to a sliding
      (type I) hiatal hernia. The hernia and concurrent upper airway obstruction
      (nasopharyngeal polyp) were diagnosed with a multi-modality approach, including
      thoracic and abdominal radiographs, abdominal ultrasound, computed tomography and
      endoscopy. Following unsuccessful attempts at medical management, lower
      esophageal incompetence was successfully treated by employing a combination of
      surgical techniques, including herniorrhaphy, esophagopexy and modified (floppy)
      Nissen fundoplication. RELEVANCE AND NOVEL INFORMATION: A multi-modality imaging
      approach was valuable in completely assessing the extent of this cat's disease.
      Although an untraditional approach, the authors report herein the first clinical
      description of the use of combined surgical techniques with the floppy Nissen
      fundoplication technique (an antireflux procedure) in a cat. This procedure was
      used as a first-line surgical technique in this cat with severe lower esophageal
      incompetence, and may be a viable option for cases non-responsive to other
      therapeutic interventions. Further investigation of this surgical technique is
      warranted.

PMID- 28491384
TI  - Bacterial pericarditis in a cat.
AB  - CASE SUMMARY: A 4-year-old male neutered domestic shorthair cat was presented to
      the Oregon State University cardiology service for suspected pericardial
      effusion. Cardiac tamponade was documented and pericardiocentesis yielded
      purulent fluid with cytologic results supportive of bacterial pericarditis. The
      microbial population consisted of Pasteurella multocida, Actinomyces canis,
      Fusobacterium and Bacteroides species. Conservative management was elected
      consisting of intravenous antibiotic therapy with ampicillin sodium/sulbactam
      sodium and metronidazole for 48 h followed by 4 weeks of oral antibiotics. Re
      examination 3 months after the initial incident indicated no recurrence of
      effusion and the cat remained free of clinical signs 2 years after presentation.
      RELEVANCE AND NOVEL INFORMATION: Bacterial pericarditis is a rare cause of
      pericardial effusion in cats. Growth of P multocida, A canis, Fusobacterium and
      Bacteroides species has not previously been documented in feline septic
      pericarditis. Conservative management with broad-spectrum antibiotics may be
      considered when further diagnostic imaging or exploratory surgery to search for a
      primary nidus of infection is not feasible or elected.

PMID- 28491385
TI  - Chronic urinary bladder torsion causing urinary incontinence in a cat.
AB  - CASE SUMMARY: A 10-month-old female spayed domestic shorthair cat was presented
      for urinary incontinence. The cat was azotaemic, and ultrasound examination
      identified hydroureter and hydronephrosis. Subsequent computed tomography (CT)
      contrast pyelography allowed a diagnosis of urinary bladder torsion. Surgical
      findings and treatment are described. Postoperatively, incontinence and azotaemia
      resolved, and marked improvements were documented with ultrasound and CT in
      urinary tract structural abnormalities. RELEVANCE AND NOVEL INFORMATION: To our
      knowledge, urinary bladder torsion has not been previously reported in the cat.
      This case most probably occurred as a complication of ovariohysterectomy, as has
      been reported in the dog; however, the presenting sign of chronic urinary
      incontinence is unique. Response to surgical correction was favourable.

PMID- 28491386
TI  - Proliferative, necrotizing and crescentic immune complex-mediated
      glomerulonephritis in a cat.
AB  - CASE SUMMARY: A 5-year-old cat was examined for vomiting and anorexia of 2 days'
      duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main
      biochemical findings. Serial analyses of the urine revealed isosthenuria,
      proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected
      surrounding the right kidney by ultrasonography. Histopathologic evaluation of
      ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent
      with proliferative, necrotizing and crescentic glomerulonephritis with fibrin
      thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic
      active interstitial nephritis. Owing to a lack of clinical improvement, the cat
      was eventually euthanized. Post-mortem renal biopsies were processed for light
      microscopy, transmission electron microscopy and immunofluorescence. This
      revealed severe focal proliferative and necrotizing glomerulonephritis with
      cellular crescent formation, podocyte injury and secondary segmental sclerosis.
      Ultrastructural analysis revealed scattered electron-dense deposits in the
      mesangium, and immunofluorescence demonstrated positive granular staining for
      lambda light chains, consistent with immune complex-mediated glomerulonephritis.
      Severe diffuse acute tubular epithelial injury and numerous red blood cell casts
      were also seen. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the
      first report of naturally occurring proliferative, necrotizing and crescentic
      immune complex glomerulonephritis in a cat.

PMID- 28491387
TI  - Lumbosacral intraspinal extradural ganglion cyst in a cat.
AB  - CASE SUMMARY: A 16-year-old neutered female domestic shorthair cat was referred
      for chronic history of reluctance to jump, stiffness of the tail and lower back
      pain. Mild pelvic limb ataxia, reduced perianal reflex and lumbosacral discomfort
      were present on neurological examination. On magnetic resonance imaging, a well
      defined rounded structure of 3 mm in diameter was identified on the right dorsal
      aspect of the epidural space at L7-S1, causing displacement of the cauda equina.
      The lesion was hyperintense to spinal cord parenchyma on T2-weighted images and
      hypointense on T1-weighted images, consistent with a fluid-filled structure. A
      Lumbosacral dorsal laminectomy was performed. A clear fluid-containing structure
      was identified between the right L7 nerve root and the cauda equina. Following
      surgical excision, histopathology confirmed the cystic nature of the lesion and
      revealed thick disorganised sheaths of fibrocollagenous tissue and flattened
      mesenchymal cells lining the luminal part of the cyst wall. A diagnosis of
      intraspinal ganglion cyst was made. The cat recovered uneventfully. Seven months
      after surgery euthanasia was performed for unrelated reasons; no neurological
      deficits were present. RELEVANCE AND NOVEL INFORMATION: This is the first
      reported case of intraspinal ganglion cyst in a cat. Intraspinal extradural cysts
      should be considered among other differential diagnoses for cats with lumbosacral
      myelopathy/radiculopathy.

PMID- 28491388
TI  - Osteitis fibrosa cystica in a domestic young cat.
AB  - CASE SUMMARY: A 4-month-old cat had bilateral swellings of the mandible, maxilla,
      humerus and femur, and angular deviations in the axial and appendicular skeleton.
      The biochemical profile indicated hypercalcemia, hyperphosphatemia and increased
      parathyroid hormone levels. Because of the poor prognosis, the cat was
      euthanized. At necropsy, malleable and fragile bones, associated with numerous
      cystic areas containing yellowish and translucent liquid, were observed.
      Histologically, the bones showed marked diffuse proliferation of fibrous
      connective tissue, and large numbers of osteoclasts surrounding numerous cystic
      structures were also observed within fibrotic areas at the periphery of the
      trabecular bone. In addition, enlargement of the parathyroid glands, which was
      associated with increased serum concentrations of calcium, phosphorus and
      parathyroid hormone, was detected. RELEVANCE AND NOVEL INFORMATION: The changes
      observed in this cat are consistent with hyperparathyroidism-associated osteitis
      fibrosa cystica, which is an unusual presentation in the cat.
      Hyperparathyroidism, either primary (neoplastic) or secondary (nutritional or
      renal), is the primary cause of this condition.

PMID- 28491389
TI  - Paraneoplastic neutrophilic leukocytosis syndrome in a cat with recurrent mammary
      carcinoma.
AB  - CASE SUMMARY: A spayed 12-year-old female domestic shorthair cat presented with
      nodular lesions on the ventral-right thoracic wall after complete mastectomy 4
      months previously. The prior diagnosis was tubulopapillary mammary carcinoma with
      axillary lymph node metastasis, and a recurrence was confirmed. A gradual and
      sequential increase in the total number of leukocytes with severe neutrophilia
      (95.632/ul) developed over the course of the illness, along with an increase in
      the size of the recurrent mass. The severe leukocytosis did not show any response
      to antibiotic therapy, and no evidence of infection was observed. Bone marrow
      cytology confirmed hypercellularity in the myeloid cell lineage. Based on these
      findings, paraneoplastic neutrophilic leukocytosis syndrome was suspected. An
      incisional biopsy of the recurrent mass was consistent with recurrent
      tubulopapillary mammary carcinoma. Malignant epithelial cells stained positive
      upon immunohistochemistry for granulocyte-macrophage colony-stimulating factor,
      cytokeratin and vimentin. After the final diagnosis of paraneoplastic
      neutrophilic leukocytosis syndrome, the cat was euthanized at the owner's
      request. RELEVANCE AND NOVEL INFORMATION: This is a novel case of paraneoplastic
      leukocytosis syndrome associated with mammary carcinoma in a cat. Although there
      are some reports describing paraneoplastic leukocytosis in cats, the relationship
      between this syndrome and feline mammary tumors has not been described.

PMID- 28491390
TI  - Extrahepatic biliary duct obstruction as a result of involuntary transcavitary
      implantation of hair in a cat.
AB  - CASE SUMMARY: A 4-year-old male neutered domestic shorthair cat was referred for
      investigation of jaundice. The cat had a recent history of a skin laceration
      repair following trauma. Sequential serum biochemistry demonstrated increasing
      plasma bilirubin concentrations; abdominal ultrasonography revealed ongoing
      pancreatitis and apparent extrahepatic obstruction of the common bile duct.
      Exploratory laparotomy identified constriction of the common bile duct with
      foreign material (cat hair). The constricting band of hair was removed
      surgically; cholecystoduodenostomy was performed. Postsurgical quality of life is
      excellent with chronic treatment of tylosin, omeprazole and ursodeoxycholic acid.
      RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first reported
      case of extrahepatic biliary duct obstruction resulting from the intra-abdominal
      migration of a foreign body, in this case, hair shafts. The mechanism by which
      this occurred was likely a combination of physical constriction by the hair
      shafts and subsequent foreign body reaction surrounding this. This should be
      included in the differential diagnosis of a cat with jaundice.

PMID- 28491391
TI  - Effect of age and surgical approach on perioperative wound complication following
      ovariohysterectomy in shelter-housed cats in Australia.
AB  - OBJECTIVES: The aim of the study was to investigate the effects of age and/or
      surgical approach on perioperative wound complication following
      ovariohysterectomy (OHE). METHODS: A retrospective search of perioperative
      monitoring records from a shelter desexing program was conducted to identify cats
      that underwent OHE between 1 June 2010 and 31 December 2012 inclusive. A wound
      complication was defined as gross observation of inflammation or wound dehiscence
      at the surgical site in the 5 day postoperative period. Cases were grouped
      according to age (<=12 weeks or >12 weeks) and surgical approach (flank or
      midline). Stratified analyses were conducted to evaluate the association between
      surgical approach and wound complications, after adjusting for age. Mantel
      Haenszel adjusted risk ratio, Cochran-Mantel-Haenszel test statistic and their
      95% confidence intervals were presented. RESULTS: A total of 312 cases met the
      study criteria. The overall wound complication risk was low (6.09%) and was not
      related to age. A midline approach was associated with a 4.59-times increased
      risk of wound complication, compared with a flank approach in cats up to 12 weeks
      of age (P = 0.015) but not in older cats. CONCLUSIONS AND RELEVANCE: These
      findings support the practice of prepubertal desexing for cats.

PMID- 28491392
TI  - Glenoidectomy for treatment of a comminuted scapular fracture in a cat.
AB  - CASE SUMMARY: This case report describes the surgical technique used and clinical
      outcome of a 15-year-old neutered female cat that had a comminuted fracture of
      the right glenoid and scapular neck secondary to a gunshot injury that was
      treated with glenoidectomy. RELEVANCE AND NOVEL INFORMATION: Good clinical
      outcomes are possible with removal of the glenoid for treatment of comminuted
      fractures of the scapulohumeral joint. Glenoidectomy is a viable alternative to
      amputation in cats with normal neurovascular supply to the affected limb.
      Persistent functional, pain-free lameness, muscle hypertrophy and changes in
      shoulder range of motion are to be expected.

PMID- 28491393
TI  - Persistent right aortic arch with an aberrant left subclavian artery, Kommerell's
      diverticulum and bicarotid trunk in a 3-year-old cat.
AB  - CASE SUMMARY: A 3-year-old male, neutered, domestic shorthair cat with a history
      of chronic regurgitation since being obtained as a kitten was presented for
      weight loss and regurgitation of all ingested food. The cat was in poor body
      condition and had a firm swelling in the ventral neck at the time of
      presentation. Thoracic radiographs showed severe dilation of the entire cervical
      and cranial intrathoracic esophagus to the level of the heart base. Computed
      tomographic angiography (CTA) showed a persistent right aortic arch with an
      aberrant left subclavian artery and severe dilation of the cervical and
      intrathoracic esophagus cranial to the heart base. CTA also showed a bicarotid
      trunk and Kommerell's diverticulum to be present, which are rare vascular
      structures in the cat. Esophagoscopy showed esophageal dilation and multiple
      compact trichobezoars obstructing the esophagus. Removal of the obstructing
      trichobezoars resulted in resolution of clinical signs, and the cat was able to
      drink water and eat a canned food slurry without regurgitation. Surgical
      correction was not pursued. RELEVANCE AND NOVEL INFORMATION: Vascular ring
      anomaly (VRA) should be considered in all cats with a history of regurgitation,
      regardless of their age at the time of presentation. CTA is a valuable diagnostic
      imaging procedure that allows differentiation of a VRA from other causes of
      esophageal obstruction and provides information about the VRA that can be used to
      determine amenability to surgical correction.

PMID- 28491394
TI  - Primary goitrous hypothyroidism in a young adult domestic longhair cat: diagnosis
      and treatment monitoring.
AB  - CASE SUMMARY: Primary goitrous hypothyroidism was diagnosed in a 12-month-old cat
      examined because of small stature, mental dullness, severe lethargy, generalized
      weakness and gait abnormalities. Radiographs of the long bones and spine revealed
      delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of primary
      hypothyroidism was confirmed by low serum concentrations of total and free
      thyroxine (T4) with high thyroid-stimulating hormone (TSH) concentrations.
      Thyroid scintigraphy revealed severe enlargement of both thyroid lobes, as
      evidenced by a seven-fold increase in calculated thyroid volume above the
      reference interval. In addition, this bilateral goiter had an extremely high
      radionuclide uptake, about 10-fold higher than the normal feline thyroid gland.
      Treatment with twice-daily levothyroxine (L-T4), administered on an empty
      stomach, resulted in increased alertness, playfulness, strength and improvement
      in gait, as well as an increase in body length and weight. L-T4 replacement also
      led to normalization of serum thyroid hormone and TSH concentrations, and
      complete resolution of goiter. RELEVANCE AND NOVEL INFORMATION: Spontaneous
      hypothyroidism is rarely reported in cats, with congenital hypothyroidism in
      kittens diagnosed most frequently. Despite the fact that this cat was a young
      adult, it likely had a form of congenital hypothyroidism caused by
      dyshormonogenesis (defect in thyroid hormone synthesis) that led to compensatory
      development of goiter. In hypothyroid cats, treatment with L-T4 is best given
      twice daily on an empty stomach to ensure adequate absorption. Normalization of
      serum TSH and shrinkage of goiter, as well as improvement in clinical signs, is
      the goal of treatment for cats with goitrous hypothyroidism.

PMID- 28491395
TI  - Probable primary polydipsia in a domestic shorthair cat.
AB  - CASE SUMMARY: A 10-month-old neutered male domestic shorthair cat presented with
      a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up
      the only abnormal findings were hyposthenuria and an elevated random plasma
      osmolality level. Trial therapy with the oral and ophthalmic forms of
      desmopressin failed to concentrate urine. A modified water deprivation test
      confirmed the ability to concentrate urine above a urine specific gravity (USG)
      of 1.035. After transitioning the cat to a higher sodium diet and instituting
      several enrichment changes to the cat's environment, average water consumption
      and urine output levels decreased to almost normal levels and USG increased from
      1.006 to 1.022. These findings provide strong evidence that primary polydipsia
      was the underlying etiology of the cat's condition. RELEVANCE AND NOVEL
      INFORMATION: This case report exemplifies the challenges faced when a cat
      presents for polyuria and polydipsia without an obvious cause identified on
      routine diagnostics. To our knowledge, this is the first report of primary
      polydipsia in a cat.

PMID- 28491396
TI  - Tetrathyridiosis in a domestic shorthair cat.
AB  - CASE SUMMARY: This report describes the clinical and parasitological findings in
      a domestic shorthair cat with isolated thoracic tetrathyridiosis. The cat was a
      stray from Malta that had lived in Germany for several years since as an indoor
      only cat. Therefore, the process of infection remains very unusual. In this case
      it must be considered that the cat had been infected years previously while in
      Malta, and had lived at least 4 years without any clinical signs. It was possible
      to diagnose this uncommon disease and initiate an effective treatment with
      fenbendazole, praziquantel and supportive care. Clinical signs, as well as
      radiographic findings, were regressive with this treatment. RELEVANCE AND NOVEL
      INFORMATION: Tetrathyridiosis is a rare finding in cats, especially in Germany,
      but it seems to be a potential differential diagnosis of pleural effusion.
      Mesocestoides corti, which was the causative parasite in this case, has not
      previously been isolated in Germany. Because tetrathyridiosis is only diagnosed
      post mortem in most cases, little is known about effective therapeutic options.
      Furthermore, clinical signs of this disease can be absent for several years and
      can potentially be triggered by neoplastic conditions or immunosuppression.
      Tetrathyridiosis seems to be a treatable disease that can be controlled by
      adequate antiparasitic therapy.

PMID- 28491397
TI  - Successful subtotal orbitectomy in a cat with osteoma.
AB  - CASE SUMMARY: A 14-year-old Siamese neutered male cat was evaluated for anorexia
      and a left periorbital mass. Skull radiographic findings showed a well-defined
      lesion resembling new compact bone formation without destruction. A subtotal
      orbitectomy was indicated. The tumor was removed intact with a normal tissue
      margin of at least 1 cm. There were no postsurgical complications.
      Histopathologic examination revealed an osteoma. The cat returned to normal
      appetite and activity 15 days after surgery. Six months after surgery, there were
      no gross signs of recurrence. RELEVANCE AND NOVEL INFORMATION: Periorbital tumors
      are infrequently diagnosed in companion animals and most are malignant. In this
      case, the diagnosis was orbital osteoma. The most commonly affected bone for
      osteoma in cats is the mandibular bone; few cases have been identified in orbital
      bones. Orbital surgery has the potential to be challenging owing to complex
      anatomy, difficult exposure and the tendency to bleed. Surgical complications are
      common. In this case, although the disease was advanced, subtotal orbitectomy was
      successfully performed.

PMID- 28491398
TI  - Adrenocortical tumor in a cat secreting more than one type of corticosteroid.
AB  - CASE SUMMARY: A 14-year-old, spayed female domestic shorthair cat was evaluated
      because of a right adrenal mass. The referring veterinarian had started treatment
      for hypokalemia and systemic arterial hypertension. During the initial evaluation
      the cat was alert and responsive, and serum potassium concentration was within
      the reference range. Serum concentrations of aldosterone and progesterone were
      increased. Atrophy of the contralateral adrenal and an exaggerated response of
      cortisol to stimulation with adrenocorticotropic hormone suggested hypersecretion
      of cortisol. Unilateral adrenalectomy was performed and recovery was uneventful.
      Histologic examination of the mass revealed an adrenocortical tumor. After
      surgery, clinical signs of hypercortisolism, hyperaldosteronism and
      hyperprogesteronism were no longer observed, and neither potassium
      supplementation nor antihypertensive treatment were needed. RELEVANCE AND NOVEL
      INFORMATION: In cases with an adrenocortical tumor, clinicians should investigate
      whether the tumor hypersecretes glucocorticoids, mineralocorticoids, sex steroids
      or combinations of these. Hypersecretion of more than one adrenal hormone may
      occur in a cat with an adrenocortical tumor.

PMID- 28491399
TI  - Antigenemia without antigenuria in a cat with histoplasmosis.
AB  - CASE SUMMARY: Based on demonstration of the yeast phase of Histoplasma capsulatum
      on fine-needle aspirate cytology of the kidney, a 5-year-old cat was diagnosed
      with histoplasmosis. Urine and serum were tested for antigen via a Histoplasma
      antigen enzyme immunoassay. At the time of diagnosis, and on multiple occasions
      during antifungal treatment, antigenemia was detected without antigenuria. The
      cat was treated with standard therapy and achieved clinical remission. RELEVANCE
      AND NOVEL INFORMATION: Diagnosis is most commonly made by finding the yeast phase
      of H capsulatum via cytology of fluid samples or cytology or histopathology of
      infected tissues. In certain cases this may require invasive tests. Recently, a
      non-invasive test, a Histoplasma antigen enzyme immunoassay, has been shown to be
      a sensitive test for supporting the diagnosis of histoplasmosis in cats. Urine
      has been considered the biologic specimen of choice for antigen testing and there
      is a paucity of information concerning the use of other specimens such as serum.
      The case herein reports a cat with antigenemia without antigenuria. These
      findings suggest that further research is necessary to better understand the
      ideal biologic sample or combination of samples as it pertains to antigen testing
      in cats. It also suggests that to maximize sensitivity both urine and serum may
      need to be tested in cats with suspected histoplasmosis.

PMID- 28491400
TI  - Congenital hepatic fibrosis and polycystic kidney disease not linked to C >A
      mutation in exon 29 of PKD1 in a Persian cat.
AB  - CASE SUMMARY: We describe the case of a 1-year-old male Persian cat diagnosed
      with congenital hepatic fibrosis (CHF) associated with renal polycystic disease
      and, for the first time, we have shown that there was no C >A mutation in exon 29
      of PKD1 (polycystic kidney disease 1). The cat presented with a history of
      chronic weight loss, anorexia, vomiting, depression and lethargy, with profuse
      salivation and ascites on clinical examination. A mild elevation in liver
      associated plasma enzymes suggested a hepatic disease. Owing to the cat's
      deteriorating condition, it was euthanized. During necropsy, the liver was found
      to be enlarged, firm and reddish, and the kidney had multiple small cortical
      cysts. Immunohistochemistry revealed that bile duct cells and epithelial cells of
      renal cysts showed positive immunoreactivity to keratin 19. Collagen fibers
      surrounding bile ducts within portal areas demonstrated reactivity to type IV
      collagen antibody, confirming the congenital nature of the process. A diagnosis
      of ductal plate malformation consistent with CHF associated with polycystic
      kidney in a young Persian cat was made. Interestingly, genetic testing revealed a
      wild-type sequence at position 3284 in exon 29 of PKD1. RELEVANCE AND NOVEL
      INFORMATION: The absence of the classic genetic mutation associated with the
      particular clinical presentation supports the hypothesis of a distinct
      etiopathogenesis among fibropolycystic diseases in domestic cats. Moreover,
      congenital hepatic fibrosis is a rare but important differential diagnosis for
      young Persian cats and their crosses with clinical signs of chronic end-stage
      liver disease.

PMID- 28491401
TI  - Nosocomial feline calicivirus-associated virulent systemic disease in a
      veterinary emergency and critical care unit in France.
AB  - CASE SERIES SUMMARY: In October 2011, an abnormally large morbidity and mortality
      event was noted in the intensive care unit (ICU) of a veterinary school hospital
      in Nantes, France. Cats, and cats only, transferred from the emergency room
      presented with fever, ulcers on the tongue and cutaneous lesions around
      venepuncture or surgical incision sites, leading to suspicion of a feline
      calicivirus-associated virulent systemic disease confirmed with reverse
      transcriptase-polymerase chain reaction. A total of 14 cats were suspected. The
      clinical features and the origin of the contamination were described for each
      cat. The median length of incubation was 4.5 days. Fifty-seven percent of the
      cats were euthanased (8/14) and 21% died (3/14), with a combined mortality of 79%
      (11/14) - the highest ever reported. Median survival was 12 days. The recovery
      rate was 21% (3/14). RELEVANCE AND NOVEL INFORMATION: Eight outbreaks have been
      reported, in veterinary clinics or in group-housed cats. The main unusual aspects
      of the present outbreak were: (1) the extreme flare-up of lesions at sites of
      skin breach, precluding any puncture/incision; (2) the suggested better survival
      rate at home than in hospital; and (3) the immediate control of the outbreak
      after recognition of the disease. Other striking but less unusual features of
      this outbreak were: (4) the increasing of the virulence of the calicivirus with
      the passage of time; and (5) the primary role that the caregivers' hands played
      in the spread of the outbreak.

PMID- 28491402
TI  - Feline paraneoplastic alopecia associated with metastasising intestinal
      carcinoma.
AB  - CASE SUMMARY: A 10-year-old male neutered British Shorthair cat was presented
      with a 6 month history of lethargy, weight loss and alopecia. Clinical
      examination revealed widespread alopecia of the ventral abdomen and hindlimbs.
      The skin in these areas was smooth and shiny and hairs could be easily epilated.
      Spontaneous pruritus was observed. Cytological examination of superficial
      impression smears showed a severe Malassezia species dermatitis and pyoderma.
      Ectoparasites could not be detected and no sign of dermatophytosis was visible in
      trichograms and Wood's lamp analysis. Abdominal ultrasound found a focally
      thickened wall of the large intestine and multiple nodules in the liver. Fine
      needle aspirates from lymph nodes, liver and altered colonic wall were consistent
      with an undifferentiated malignant neoplasia. The cat was euthanased at the
      owners' request, owing to potential neoplasia with metastatic spread. At necropsy
      a metastasising carcinoma of the colonic wall was found, as well as a
      paraneoplastic alopecia. RELEVANCE AND NOVEL INFORMATION: Feline paraneoplastic
      alopecia has been reported in association with pancreatic carcinoma, bile duct
      carcinoma and hepatocellular carcinoma, as well as with neuroendocrine pancreatic
      carcinoma and hepatosplenic plasma cell tumour. This is the first reported case
      of feline paraneoplastic alopecia associated with a colon carcinoma.

PMID- 28491403
TI  - Trichomonosis in cats with diarrhoea in Hong Kong, China, between 2009 and 2014.
AB  - CASE SERIES SUMMARY: Infection of the domestic cat by Tritrichomonas blagburni,
      previously referred to as T foetus, may lead to a disease called feline
      trichomonosis, which manifests clinically as large bowel diarrhoea. The disease
      has a wide geographical distribution, including numerous countries in Europe,
      North America and Australia/Oceania. Nevertheless, it has occasionally been
      reported in Asia, South Korea and Japan. A retrospective study was carried out to
      include all domestic cats with diarrhoea, presented to two veterinary clinics in
      Hong Kong, China, between 1 July 2009 and 30 June 2014. A total of 29 cats with
      diarrhoea were diagnosed with Tritrichomonas species infection by means of
      quantitative PCR and direct microscopy. Tritrichomonas species was more
      frequently found in young (median age 10 months), male (66%) and purebred cats
      (86%). Giardia species was found in 31% of Tritrichomonas species-positive cats.
      The recommended dose of ronidazole (30 mg/kg q24h for 14 days) resolved clinical
      signs in 83% of diagnosed cats. RELEVANCE AND NOVEL INFORMATION: This case series
      describes Tritrichomonas species as a cause for feline chronic diarrhoea in cats
      in China. The high rate of failure (17%) in those cats receiving a standard
      regimen of ronidazole might be due to owner or patient compliance rather than
      protozoal resistance to the drug.

PMID- 28491404
TI  - Surgical resolution of an oesophageal duplication cyst causing regurgitation in a
      domestic shorthair cat.
AB  - CASE SUMMARY: An 18-month-old female domestic shorthair cat was referred for
      investigation of a 6 month period of regurgitation. Contrast radiography
      indicated an intramural oesophageal structure. Ultrasound-guided fine-needle
      aspiration of the area retrieved viscous fluid containing high numbers of
      squamous epithelial cells. Computed tomography disclosed a thin-walled contrast
      enhancing structure containing non-enhancing homogenous contents. Exploratory
      thoracotomy confirmed an intramural cystic oesophageal structure, which was
      resected. Histopathological analysis of the resected tissue demonstrated an
      intramural oesophageal duplication cyst. A 12 month follow-up period has seen
      complete resolution of the cat's clinical signs. RELEVANCE AND NOVEL INFORMATION:
      This is the first report of successful oesophageal duplication cyst removal in a
      cat. Oesophageal duplication cysts should be included on the differential list
      for dysphagia and regurgitation in cats. Complete surgical removal in this cat
      carried a good long-term outcome.

PMID- 28491405
TI  - Aldosterone and progesterone-secreting adrenocortical adenocarcinoma in a cat
      with a concurrent meningioma.
AB  - CASE SUMMARY: A 12-year-old, male neutered domestic shorthair cat was referred
      for investigation of suspected hyperaldosteronism due to persistent hypokalaemia,
      hindlimb ataxia, weakness of 1 month's duration and a left adrenal mass that was
      detected on abdominal ultrasound. Neurological examination findings at referral
      were suggestive of a concurrent left forebrain lesion. Hyperaldosteronism and
      concurrent hyperprogesteronism were confirmed on endocrine testing. On computed
      tomography (CT) of the abdomen and thorax there was no evidence of local vascular
      invasion by the adrenal mass or of metastatic disease. CT and magnetic resonance
      imaging featured a large, focal rim-enhancing extra-axial left forebrain lesion
      consistent with a meningioma. Surgical excision of the forebrain mass was
      followed by adrenalectomy 2 weeks later. The tumours were classified on
      histopathology as a psammomatous meningioma and an adrenocortical adenocarcinoma,
      respectively. Immunohistochemical staining of the meningioma confirmed the
      presence of progesterone receptors. The cat remains well 2 years later. RELEVANCE
      AND NOVEL INFORMATION: In humans, elevated serum progesterone levels have been
      associated with rapid growth of meningiomas due to the presence of progesterone
      receptors on the tumour. This is the first report of a cat with a progesterone
      and aldosterone-secreting adrenocortical adenocarcinoma and a concurrent
      meningioma. Clinicians should be aware of the potential effect of elevated
      progesterone on meningiomas in cats.

PMID- 28491406
TI  - Cutaneous squamous cell carcinoma manifesting as follicular isthmus cysts in a
      cat.
AB  - CASE SUMMARY: A 9-year-old spayed female domestic shorthair cat was examined for
      swelling of the right upper lip. The cat had been receiving oral ciclosporin A
      for eosinophilic plaques. The swelling appeared clinically and cytologically
      consistent with an abscess; exudate was cultured and treatment consisted of
      antibiotic therapy and surgical curettage. Five months of antibiotic therapy with
      three separate surgical treatments resulted in minimal improvement; three
      separate biopsy samples demonstrated epithelial cysts with severe dermal
      inflammation. Swelling and drainage of purulent material from the affected lip
      persisted and progressed to involve the left upper lip. Euthanasia was elected 13
      months after initial examination due to disease progression. On necropsy,
      histopathology demonstrated multiple isthmus cysts intermixed with squamous cell
      carcinoma (SCC). RELEVANCE AND NOVEL INFORMATION: The clinical and
      histopathologic features were unusual for feline cutaneous SCC. The cystic nature
      and lack of epidermal involvement suggest the tumor arose from non-epidermal
      squamous cells such as follicular isthmus or ductal epithelium. There is a
      pattern of SCC recognized in human renal transplant patients with features of
      epidermal inclusion cysts. These features have not been previously reported in
      SCC from a cat.

PMID- 28491407
TI  - Uterine prolapse with endometrial eversion in association with an unusual
      diffuse, polypoid, fibrosing perimetritis and parametritis in a cat.
AB  - CASE SUMMARY: This case describes a young non-pregnant cat that presented with
      uterine prolapse in association with an unusual diffuse, polypoid, fibrosing
      perimetritis and parametritis. Following ovariohysterectomy the cat recovered
      fully. No intra-abdominal complications were seen on ultrasound examination 3
      months postsurgery. At the time of writing, the cat remains healthy. RELEVANCE
      AND NOVEL INFORMATION: Uterine prolapse in the cat is relatively rare and usually
      associated with the periparturient period. Inflammatory polypoid perimetritis and
      parametritis have not previously been documented in cats, and in dogs have only
      been reported in association with the administration of oestrogenic compounds.
      The polypoid inflammation affecting the uterus and parametrium may have
      contributed to increased laxity of the uterine ligaments and predisposed to the
      development of uterine prolapse.

PMID- 28491408
TI  - Benign cementoblastoma (true cementoma) in a cat.
AB  - CASE SUMMARY: A 10-year-old castrated male domestic shorthair cat was presented
      for assessment of a gingival mass surrounding the left maxillary third and fourth
      premolar teeth. The mass was surgically removed by means of a marginal rim
      excision, and the tissue was submitted for histological assessment. It was
      identified as a benign cementoblastoma (true cementoma). There was proliferation
      of mineralized eosinophilic material with multiple irregularly placed lacunae and
      reversal lines, reminiscent of cementum. The cat recovered uneventfully from the
      anesthesia, and there was no evidence of tumor recurrence 6 months after surgery.
      RELEVANCE AND NOVEL INFORMATION: Cementoblastomas (true cementomas) in domestic
      animals are rare, with just a few reports in ruminants, monogastric herbivores
      and rodents. Cementoblastoma is considered a benign tumor that arises from the
      tooth root. The slow, expansive and constant growth that characterizes these
      masses may be accompanied by signs of oral discomfort and dysphagia. This case
      report is intended to increase knowledge regarding this tumor in cats and also
      highlights the importance of complete excision of the neoplasm. To our knowledge,
      there are no previous reports in the literature of cementoblastoma in the cat.

PMID- 28491409
TI  - The first volume of JFMS Open Reports.

PMID- 28491410
TI  - Lumbosacral agenesis in a cat.
AB  - CASE SUMMARY: Lumbosacral agenesis is a rare congenital condition reported in
      children. We report a 17-week-old female domestic shorthair cat with lumbosacral
      agenesis on whole-body radiographs. The cat was euthanized shortly thereafter
      presentation. A necropsy was not permitted. RELEVANCE AND NOVEL INFORMATION: This
      is the first reported feline case of lumbosacral agenesis.

PMID- 28491411
TI  - Successful treatment of feline leishmaniosis using a combination of allopurinol
      and N-methyl-glucamine antimoniate.
AB  - CASE SUMMARY: This work describes the diagnosis and successful treatment of a 2
      year-old domestic cat infected with Leishmania species and presenting fever, and
      ulcerative and nodular skin lesions after being treated for pyodermatitis for 1
      year without clinical improvement. After anamnesis the cat was submitted to a
      complete clinical examination. Blood was collected for determination of
      haematological and biochemical parameters, detection of feline leukaemia virus
      (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV) and
      Leishmania amastigotes. Fine-needle aspiration puncture from the skin nodules was
      also performed. After definitive diagnosis the animal was treated and followed up
      over a 2 year period. The animal tested negative for FIV-specific antibodies,
      FeLV antigen and feline coronavirus RNA. Leishmania amastigotes in the skin
      nodules were confirmed by cytology and molecular diagnosis. Treatment was
      initiated with allopurinol, resulting in a slight clinical improvement. Thus, N
      methyl-glucamine antimoniate was added and administered for 30 days, with
      complete closure of the ulcerative lesions in the hindlimbs requiring a surgical
      approach. Close monitoring of the patient in the following 24 months indicated
      that combined therapy was safe and clinical cure was achieved without further
      relapses or side effects. RELEVANCE AND NOVEL INFORMATION: Considering the
      increasing number of feline leishmaniosis cases and the inconsistent results of
      most therapeutic protocols described in the literature, the use of new
      approaches, especially in refractory cases, is essential. Although the use of
      allopurinol and N-methyl-glucamine antimoniate is off-label in cats, in this case
      the combination treatment was followed by an extensive analytical monitoring,
      supporting their safety and effectiveness.

PMID- 28491413
TI  - Intra-parenchymal brainstem haemorrhage secondary to iatrogenic needle injury
      after a parenteral injection in a cat.
AB  - CASE SUMMARY: A 6-month-old female domestic shorthair cat was presented with
      acute onset non-ambulatory right hemiparesis and horizontal nystagmus following
      an injection attempt in the neck, during which the cat did not cooperate.
      Magnetic resonance imaging (MRI) revealed a well-defined intra-axial lesion on
      the right side of the myelencephalon. The lesion was T2-weighted hypointense and
      T1-weighted hypointense to isointense to grey matter, non-contrast enhancing,
      with perilesional oedema and signal void on T2*-weighted images. A linear
      hyperintense lesion in the muscles of the right dorsolateral aspect of the neck
      on short tau inversion recovery images was also observed. These MRI findings were
      consistent with iatrogenic brainstem haemorrhage and a muscle needle tract. The
      cat made a good recovery with just mild residual neurological deficits 6 weeks
      after the injury. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the
      first report of an iatrogenic brainstem needle injury in a cat and the first
      report of a central nervous system iatrogenic trauma after a parenteral
      injection. Care should be taken with neck parenteral injections, especially in
      the cranial cervical area.

PMID- 28491412
TI  - Distal polyneuropathy in an adult Birman cat with toxoplasmosis.
AB  - CASE SUMMARY: A 6-year-old female spayed Birman cat presented with a history of
      weight loss, stiff and short-strided gait in the pelvic limbs and reluctance to
      jump, progressing to non-ambulatory tetraparesis over 6 weeks. Poor body
      condition, dehydration and generalised muscle wastage were evident on general
      examination. Neurological examination revealed mildly depressed mental status,
      non-ambulatory flaccid tetraparesis and severely decreased proprioception and
      spinal reflexes in all four limbs. The neuroanatomical localisation was to the
      peripheral nervous system. Haematology, feline immunodeficiency virus/feline
      leukaemia virus serology, serum biochemistry, including creatine kinase and
      thyroxine, thoracic radiographs and abdominal ultrasound did not reveal
      significant abnormalities. Electromyography revealed fibrillation potentials and
      positive sharp waves in axial and appendicular muscles. Decreased motor
      conduction velocities and compound muscle action potential amplitudes were
      detected in ulnar and sciatic-tibial nerves. Residual latency was increased in
      the sciatic-tibial nerve. Histologically, several intramuscular nerve branches
      were depleted of myelinated fibres and a few showed mononuclear infiltrations.
      Toxoplasma gondii serology titres were compatible with active toxoplasmosis. Four
      days after treatment initiation with oral clindamycin the cat recovered the
      ability to walk. T gondii serology titres and neurological examination were
      normal after 11 and 16 weeks, respectively. Clindamycin was discontinued after 16
      weeks. One year after presentation the cat showed mild relapse of clinical signs
      and seroconversion, which again resolved following treatment with clindamycin.
      RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of
      distal polyneuropathy associated with toxoplasmosis in a cat. This case suggests
      the inclusion of toxoplasmosis as a possible differential diagnosis for acquired
      polyneuropathies in cats.

PMID- 28491414
TI  - Morphine-induced pruritus after epidural administration followed by treatment
      with naloxone in a cat.
AB  - CASE SUMMARY: A young male domestic shorthair cat weighing 1.6 kg was admitted to
      a veterinary teaching hospital for elective orchiectomy. A lumbosacral epidural
      injection of preservative-free morphine (0.1 mg/kg) and lidocaine (0.25 ml/kg)
      was performed under general anesthesia. One hour after extubation, the cat became
      agitated. Severe licking and biting of the hindlimbs, tail and lumbar area were
      observed. Pruritus was suspected and likely to be caused by epidural morphine.
      Acepromazine (0.02 mg/kg IM) was administered but clinical signs did not cease.
      Naloxone (2 ug/kg IV) was administered and clinical signs resolved within 20
      mins. RELEVANCE AND NOVEL INFORMATION: Different therapeutic approaches are
      available for the treatment of morphine-induced pruritus. This case describes an
      additional treatment option using opioid antagonism with naloxone.

PMID- 28491415
TI  - Prevalence of selected infectious disease agents in stray cats in Catalonia,
      Spain.
AB  - OBJECTIVES: The objective of the current study was to investigate the prevalence
      rates of the following infectious agents in 116 stray cats in the Barcelona area
      of Spain: Anaplasma phagocytophilum, Bartonella species, Borrelia burgdorferi,
      Chlamydia felis, Dirofilaria immitis, Ehrlichia species, feline calicivirus
      (FCV), feline herpesvirus-1 (FHV-1), feline leukaemia virus (FeLV), feline
      immunodeficiency virus (FIV), haemoplasmas, Mycoplasma species and Rickettsia
      species. METHODS: Serum antibodies were used to estimate the prevalence of
      exposure to A phagocytophilum, Bartonella species, B burgdorferi, Ehrlichia
      species and FIV; serum antigens were used to assess for infection by D immitis
      and FeLV; and molecular assays were used to amplify nucleic acids of Anaplasma
      species, Bartonella species, C felis, D immitis, Ehrlichia species, FCV, FHV-1,
      haemoplasmas, Mycoplasma species and Rickettsia species from blood and nasal or
      oral swabs. RESULTS: Of the 116 cats, 63 (54.3%) had evidence of infection by
      Bartonella species, FeLV, FIV or a haemoplasma. Anaplasma species, Ehrlichia
      species or Rickettsia species DNA was not amplified from these cats. A total of
      18/116 cats (15.5%) were positive for FCV RNA (six cats), Mycoplasma species DNA
      (six cats), FHV-1 DNA (three cats) or C felis DNA (three cats). CONCLUSIONS AND
      RELEVANCE: This study documents that shelter cats in Catalonia are exposed to
      many infectious agents with clinical and zoonotic significance, and that flea
      control is indicated for cats in the region.

PMID- 28491417
TI  - Dorsally located corneal dermoid in a cat.
AB  - CASE SUMMARY: A 2-month-old, male kitten was presented for evaluation of
      unilateral blepharospasm and epiphora involving the right eye. Ocular examination
      revealed conjunctivitis, a superficial corneal ulcer, reflex anterior uveitis and
      a haired mass within the dorsal cornea of the right eye. The mass was
      subsequently removed surgically via a lamellar keratectomy. Histologic evaluation
      of the mass via light microscopy revealed it to be comprised of normal-haired
      skin with mild inflammation. One week after surgical removal and medical
      management of the corneal ulcer, all ocular clinical signs had resolved with
      minimal corneal scarring. On re-examination 6 months following surgical excision
      of the mass, the kitten was noted to be comfortable with no significant corneal
      scarring. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first
      case report of a dorsally located corneal dermoid in a cat.

PMID- 28491416
TI  - Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia
      in a cat.
AB  - CASE SUMMARY: A 14-year-old, female neutered domestic shorthair presented for
      dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous
      mass was present within the pericardial sac, and the mass continued caudally with
      the mesenteric fat. On CT, the outline of the diaphragm was not continuous and
      there was an obvious defect with diaphragmatic thickening present at the mid
      level of the liver. A pleural effusion and a small-volume pericardial effusion
      were also present. A ventral midline coeliotomy and median sternotomy revealed a
      5 * 6 * 7 cm firm, irregular, tan-coloured soft tissue mass within the
      pericardial sac attached to both the diaphragmatic defect and liver. The mass was
      carefully dissected away from the heart and the diaphragmatic defect was repaired
      with primary closure. Postoperatively, the cat had a persistent pneumothorax that
      required continuous pleural suction for 41 h. The cat died 44 h postoperatively.
      Histopathology and immunohistochemistry confirmed the mass to be a hepatic
      fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH).
      RELEVANCE AND NOVEL INFORMATION: This is the first reported case of metaplastic
      transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic
      fibrosarcoma is a rarely reported location for fibrosarcoma in this species.

PMID- 28491418
TI  - Hybrid technique coil embolisation for intrahepatic arterioportal fistula in a
      cat: case report.
AB  - CASE SUMMARY: A 13-month-old, female, mixed breed, 4.0 kg cat was referred with a
      6 month history of decreased appetite, loss of vigour and intermittent vomiting.
      Physical examination revealed no cyanosis or wasting, and no audible heart murmur
      was auscultated. Blood profile revealed mild anaemia and mildly elevated
      postprandial serum ammonia (109 ug/dl). Abdominal ultrasonography revealed
      dilation of an intrahepatic portal vein branch and an intrahepatic aneurysm, with
      splenomegaly and ascites. Hepatic arteriovenous fistula/hepatic artery-portal
      vein fistula with multiple acquired portosystemic shunts was strongly suspected.
      Medical control was achieved using antibiotics, liver-protecting agents, a low
      protein diet and blood transfusions. However, because medical treatment proved
      ineffective, coil embolisation was performed on day 11, using a hybrid approach
      via the mesenteric vein. Subsequent follow-up showed good appetite, with no signs
      of diarrhoea or ascites. Abdominal ultrasonography revealed that the mosaic
      pattern around the site of coil placement in the portal vein branch had improved
      and pulsatility had disappeared. RELEVANCE AND NOVEL INFORMATION: Intrahepatic
      arterioportal fistula involves a circulatory shunt between the hepatic artery and
      the hepatic or portal vein within the liver, and may be congenital or acquired.
      Both forms have been reported in humans, but most cases in cats have been
      congenital. Few reports have described treatment methods or prognosis in cats. We
      report here that coil embolisation using a hybrid approach is a procedure
      offering easy, effective treatment by blocking hepatofugal blood flow.

PMID- 28491419
TI  - Retrograde migration and subcutaneous coiling of the peritoneal catheter of a
      ventriculoperitoneal shunt in a cat.
AB  - Case summary Ventriculoperitoneal shunt placement is the most commonly utilised
      surgical treatment for hydrocephalus in human and veterinary patients. Migration
      of the peritoneal catheter is an uncommon but well-documented complication in
      people, usually occurring within the first 3 months postoperatively, although
      only a single feline case report exists. A ventriculoperitoneal shunt was placed
      in a domestic shorthair cat, aged 4 years and 10 months, following a diagnosis,
      with MRI, of unilateral, non-communicating hydrocephalus. Diarrhoea, increased
      vocalisation and pruritus were reported within the first 3 months
      postoperatively. A shunt-associated seroma developed, which was aspirated under
      ultrasound guidance. Within 3 days, the entire peritoneal catheter was
      subcutaneously coiled at the level of the seroma. The peritoneal catheter was
      replaced within the abdomen via a new subcutaneous tunnel. No further
      complications had occurred 24 months following revision surgery. Relevance and
      novel information This is the second report describing peritoneal catheter
      migration in a cat. Repetitive head and neck movements during self-grooming,
      raised intra-abdominal pressure secondary to vocalisation and tenesmus, and
      negative pressure exerted during seroma aspiration may have contributed to
      ventriculoperitoneal shunt migration. Excessive loose skin and increased activity
      may further increase the risk of migration in cats. Diagnostic imaging should be
      offered prior to and following aspiration of shunt-associated swellings, and
      minimal negative pressure should be exerted. Attempts to reduce the frequency of
      postoperative self-grooming, prevention and prompt treatment of conditions
      predisposing to raised intra-abdominal pressure and moderate exercise
      restriction, particularly within the first 3 months, may help reduce the risk of
      peritoneal catheter migration.

PMID- 28491420
TI  - Seroprevalence of feline immunodeficiency virus and feline leukaemia virus in
      Australia: risk factors for infection and geographical influences (2011-2013).
AB  - OBJECTIVES: Our aim was to: (i) determine the current seroprevalence of feline
      immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) in three large
      cohorts of cats from Australia; and (ii) investigate potential risk factors for
      retroviral infection. METHODS: Cohort 1 (n = 2151 for FIV, n = 2241 for FeLV)
      consisted of cats surrendered to a shelter on the west coast of Australia (Perth,
      Western Australia [WA]). Cohort 2 (n = 2083 for FIV, n = 2032 for FeLV) consisted
      of client-owned cats with outdoor access recruited from around Australia through
      participating veterinary clinics. Cohort 3 (n = 169 for FIV, n = 166 for FeLV)
      consisted of cats presenting to Murdoch University Veterinary Hospital for a
      variety of reasons. Fresh whole blood was collected and tested using a
      commercially available point-of-care lateral flow ELISA kit that detects p27 FeLV
      antigen and antibodies to FIV antigens (p15 and p24) (cohorts 1 and 2), or one of
      two lateral flow immunochromatography kits that detect p27 antigen and antibodies
      to FIV antigen (p24 and/or gp40) (cohort 3). Data recorded for cats in cohort 2
      included signalment, presenting complaint and postcode, allowing investigation of
      risk factors for FIV or FeLV infection, as well as potential geographical 'hot
      spots' for infection. RESULTS: The seroprevalence of FIV was 6% (cohort 1), 15%
      (cohort 2) and 14% (cohort 3), while the seroprevalence of FeLV was 1%, 2% and 4%
      in the same respective cohorts. Risk factors for FIV infection among cats in
      cohort 2 included age (>3 years), sex (male), neutering status (entire males) and
      location (WA had a significantly higher FIV seroprevalence compared with the
      Australian Capital Territory, New South Wales and Victoria). Risk factors for
      FeLV infection among cats in cohort 2 included health status ('sick') and
      location (WA cats were approximately three times more likely to be FeLV-infected
      compared with the rest of Australia). No geographical hot spots of FIV infection
      were identified. CONCLUSIONS AND RELEVANCE: Both FIV and FeLV remain important
      infections among Australian cats. WA has a higher seroprevalence of both feline
      retroviruses compared with the rest of Australia, which has been noted in
      previous studies. A lower neutering rate for client-owned male cats is likely
      responsible for the higher seroprevalence of FIV infection in WA cats, while the
      reason for the higher seroprevalence of FeLV in WA cats is currently unknown.

PMID- 28491421
TI  - Medical management of gastrinoma in a cat.
AB  - CASE SUMMARY: A 7-year-old male castrated domestic short-haired cat was evaluated
      for a 4 week history of intermittent vomiting, ptyalism, lethargy and weight
      loss. Serum biochemistry revealed mild mixed hepatopathy. Abdominal
      ultrasonography identified multiple heterogeneous hepatic masses and a linear,
      hyperechoic focus with associated reverberation artifact in the wall of the
      stomach consistent with a gastric ulcer. Serum gastrin concentrations were
      markedly increased. Cytologic interpretation of a fine-needle aspirate of the
      hepatic masses was consistent with neuroendocrine neoplasia, and a diagnosis of
      gastrinoma was established. Deterioration of the cat's condition, despite at-home
      acid-suppressant therapy, led to hospitalization. The cat was initially
      stabilized with intravenous crystalloid fluid therapy, maropitant, pantoprazole
      and octreotide. A continuous radiotelemetric intragastric pH monitoring system
      was used to monitor the response of intragastric pH to therapy. Long-term therapy
      was continued with omeprazole (orally q12h), octreotide (subcutaneously q8h) and
      thrice-weekly toceranib administered orally. Toceranib therapy led to
      gastrointestinal upset and was discontinued. Gastric ulceration resolved within 8
      weeks, and palliation of clinical signs was achieved for approximately 5 months.
      RELEVANCE AND NOVEL INFORMATION: Including this report, only six cases of feline
      gastrinoma have been reported in the veterinary literature. Little is known
      regarding non-surgical therapy, and octreotide has not been previously reported
      for medical management of feline gastrinoma. Results of intragastric pH
      monitoring and clinical improvement suggest that medical therapy using octreotide
      and proton pump inhibitors represents a novel therapeutic option for cats with
      gastrinoma where surgical excision is not feasible.

PMID- 28491422
TI  - Diagnosis of Aelurostrongylus abstrusus verminous pneumonia via sonography-guided
      fine-needle pulmonary parenchymal aspiration in a cat.
AB  - Case summary A 9-year-old, male neutered, indoor-outdoor domestic shorthair cat
      from the northern Alabama countryside presented for a 3 week history of coughing,
      lethargy and an episode of self-resolving dyspnea that occurred 1 week prior to
      presentation. Three-view thoracic radiographs revealed a moderate-to-severe,
      diffuse, mixed bronchial to structured interstitial (miliary-to-nodular)
      pulmonary pattern in all lung lobes with peribronchial cuffing and multifocal
      areas of mild patchy alveolar opacity. Ultrasound-guided evaluation and fine
      needle aspiration of the caudodorsal lung parenchyma was performed with sedation.
      Cytology revealed many widely scattered Aelurostrongylus abstrusus larvae and
      ova. Upon the confirmed diagnosis of A abstrusus verminous pneumonia, treatment
      with fenbendazole and selamectin resulted in complete resolution of clinical
      signs within 6 weeks of the initial diagnosis. Relevance and novel information We
      report herein the first documented case in the Americas of A abstrusus verminous
      pneumonia diagnosed via cytologic evaluation of an in vivo, percutaneous
      ultrasound-guided fine-needle aspirate of affected lung. Additionally, to our
      knowledge, we offer the first account of the sonographic (pulmonary) features of
      the disease.

PMID- 28491423
TI  - Acromegaly in a non-diabetic cat.
AB  - CASE SUMMARY: A 14-year-old, neutered male European shorthair cat was evaluated
      for a routine health check. The owner did not report any clinical signs except
      for respiratory stridor. On physical examination the main findings were broad
      facial features and increased interdental spaces. On haematology, a mild, non
      regenerative anaemia was detected, whereas the serum biochemistry profile and
      urinalysis were unremarkable. The serum glucose concentration was within the
      reference interval. Serum insulin-like growth factor-1 concentration was markedly
      elevated (>1600 ng/ml). The basal serum growth hormone concentration was elevated
      and decreased only mildly after somatostatin administration. Basal serum insulin
      concentration was high, and the insulin concentration increased considerably
      after glucose loading, consistent with insulin resistance. CT scanning of the
      skull showed an enlarged pituitary gland and increased skull bone thickness. The
      final diagnosis was acromegaly. RELEVANCE AND NOVEL INFORMATION: These findings
      demonstrate that acromegaly should be pursued and suspected in cats other than
      those with diabetes mellitus.

PMID- 28491424
TI  - Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for
      magnetic resonance imaging.
AB  - Case summary This case report describes the clinical signs and treatment of an
      alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI.
      The cat was discharged from hospital following a prolonged recovery including
      obtunded mentation and cardiorespiratory depression for several hours following
      cessation of anaesthesia. The cat received supportive therapy that included
      supplemental oxygen via a face mask, intravenous crystalloid fluids and active
      rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its
      pharmacokinetics and previously reported lethal doses are discussed. Strategies
      for reducing the incidence of medication errors are presented. Relevance and
      novel information An unintentional overdose of alfaxalone by continuous rate
      infusion has not been reported previously in a cat. Treatment is supportive and
      directed towards maintenance of the cardiorespiratory systems. Whenever possible,
      smart pumps that have been designed to reduce human error should be used to help
      prevent medication errors associated with continuous rate infusions.

PMID- 28491425
TI  - Lungworm Eucoleus aerophilus (Capillaria aerophila) infection in a feline
      immunodeficiency virus-positive cat in France.
AB  - CASE SUMMARY: A 2-year-old domestic shorthair female outdoor cat living in France
      was diagnosed with a lungworm infection due to Eucoleus aerophilus. The history
      and clinical signs, in association with bronchoscopic examination, suggested
      chronic upper respiratory disease. Cytological examination of bronchoalveolar
      lavage fluid (BALF) was consistent with suppurative bronchitis. Direct
      microscopic examination of BALF enabled the identification of E aerophilus ova.
      RELEVANCE AND NOVEL INFORMATION: The cat was positive for feline immunodeficiency
      virus and had been treated with steroids for a suspected allergic bronchitis,
      suggesting that immunodeficiency was probably a facilitating factor for E
      aerophilus infection, as described in previous cases. This case report emphasises
      the importance of considering eucoleosis (capillariosis) in the differential
      diagnosis of respiratory disease in cats. To our knowledge, this is the first
      clinical case of E aerophilus infection described in a domestic cat in France.

PMID- 28491426
TI  - Stevens-Johnson syndrome/toxic epidermal necrolysis caused by cefadroxil in a
      cat.
AB  - CASE SUMMARY: A 5-year-old, spayed female, indoor-only domestic shorthair cat was
      referred with an acute history of multifocal cutaneous and mucocutaneous erosive
      ulcerative lesions and skin detachment. The lesions occurred on the seventh day
      of therapy with cefadroxil. Erosive-ulcerative and occasionally crusted lesions
      were apparent on the medial and lateral canthus of both eyes, ventral neck,
      abdomen, perivulvar region, periungual skin and medial aspect of the front and
      hindlimbs. Diffuse and severe exfoliation was present on the dorsum and tail base
      and in both external ear canals. The cat was also dehydrated, tachycardic and
      febrile. Histopathological examination revealed extensive epidermal ulceration,
      interface dermatitis with vacuolar degeneration, apoptosis at multiple epidermal
      levels and basal, suprabasal and spinous dermoepidermal detachment. The
      histopathological diagnosis was consistent with Stevens-Johnson syndrome/toxic
      epidermal necrolysis (SJS/TEN). The recently reported Algorithm of Drug Causality
      in Epidermal Necrolysis (ALDEN), currently used in human medicine, was applied
      and a score of +6 was calculated; this supported the view that SJS/TEN in this
      cat was very likely to be associated with cefadroxil administration. RELEVANCE
      AND NOVEL INFORMATION: This clinical communication reports cefadroxil as a very
      probable cause of SJS/TEN in a cat; the ALDEN was applied in this case and
      supported diagnosis.

PMID- 28491427
TI  - Sinonasal aspergillosis in a British Shorthair cat in the UK.
AB  - Case summary A 13-year-old, castrated male, British Shorthair cat presented for
      investigation of chronic, intermittent, bilateral epistaxis and stertor. CT
      revealed severe asymmetric bilateral intranasal involvement with extensive
      turbinate lysis, increased soft tissue attenuation and lysis of the
      sphenopalatine bone and cribriform plate. On retroflexed pharyngoscopy, a plaque
      like mass occluded the choanae. Rostral rhinoscopic examination revealed
      extensive loss of nasal turbinates, necrotic tissue and mucosal fungal plaques in
      the left nasal cavity. The right nasal cavity was less severely affected. The
      nasal cavities were debrided extensively of plaques and necrotic tissue.
      Aspergillus fumigatus was isolated on fungal culture, and species identity was
      confirmed using comparative sequence analysis of the partial beta-tubulin gene.
      On histopathology of nasal biopsies, there was ulcerative lymphoplasmacytic and
      neutrophilic rhinitis, and fungal hyphae were identified on nasal mucosa,
      consistent with a non-invasive mycosis. The cat was treated with oral
      itraconazole after endoscopic debridement, but signs relapsed 4.5 months from
      diagnosis. Residual left nasal fungal plaques were again debrided endoscopically
      and oral posaconazole was administered for 6 months. Fourteen months from
      diagnosis, the cat remains clinically well with mild intermittent left nasal
      discharge secondary to atrophic rhinitis. Relevance and novel information This is
      the first case of rhinoscopically confirmed sinonasal aspergillosis to be
      diagnosed in a cat in the UK. Endoscopic confirmation of resolution of infection
      is useful in cases where mild nasal discharge persists after treatment.

PMID- 28491428
TI  - Chronic intestinal pseudo-obstruction associated with enteric ganglionitis in a
      Persian cat.
AB  - Case summary A 7-year-old neutered male Persian cat was presented for acute
      vomiting and inappetence. Physical examination revealed severe abdominal
      distension. Radiographs demonstrated pneumoperitoneum, megaoesophagus and
      generalised gaseous distension of the digestive tract. Exploratory coeliotomy was
      performed, revealing markedly distended and thickened small and large intestines
      with no observable peristalsis. No intestinal perforation was present.
      Bacteriological and cytological analysis of abdominal fluid revealed a septic
      peritonitis involving Pasteurella multocida. Full-thickness intestinal biopsies
      demonstrated lymphocytic ganglioneuritis localised to the enteric nervous system,
      in association with glandular atrophy and muscular layer hypertrophy. Amoxicillin
      clavulanate and analgesics were given. The cat's general condition gradually
      improved after the addition of pyridostigmine bromide (0.5 mg/kg q12h PO),
      initiated 3 days postsurgery. Vomiting resolved and did not recur. Follow-up
      radiographs at 15 days, and 1 and 6 months showed persistent intestinal ileus,
      milder than on the pretreatment radiographs. Thirty months after presentation the
      cat is still alive, without clinical signs, and receives 1 mg/kg q12h
      pyridostigmine. Relevance and novel information To our knowledge, this is the
      first case of ganglioneuritis of the myenteric plexus described in cats, as well
      as the first one successfully treated with pyridostigmine. Chronic intestinal
      pseudo-obstruction is a very rare condition in cats but should be included in the
      differential diagnosis of generalised gastrointestinal ileus.

PMID- 28491429
TI  - Prevalence of Cytauxzoon felis infection in healthy free-roaming cats in north
      central Oklahoma and central Iowa.
AB  - Case summary Cytauxzoonosis is a tick-borne disease of cats, and Oklahoma (OK),
      USA, is considered an enzootic state. To determine the prevalence of Cytauxzoon
      felis, blood was collected from free-roaming cats, as they are frequently exposed
      to tick vectors. Our objective was to determine the prevalence of C felis
      infection in free-roaming cats in north-central Oklahoma and central Iowa (IA).
      Infection with C felis was determined using DNA extracted from blood and PCR
      amplification. Blood was collected from 380 free-roaming cats between January and
      April in 2014 in OK. DNA from C felis was detected in 3/380 (0.8%; 95%
      confidential interval [CI] 0.22-2.3%). In IA, 292 blood samples were collected
      between 2012 and 2014. No C felis-infected cats were detected (0; 95% CI 0-0%).
      Relevance and novel information The prevalence of C felis (0.8%) in north-central
      OK reported herein was lower than the previously reported 3.4% in domestic cats
      in OK. Our study supports that the prevalence in a given enzootic area can vary
      by location and from the pool of cats sampled. None of 291 (0%) cats were
      infected with C felis in central IA. To date, only one case of cytauxzoonosis in
      a domestic cat has been reported in IA. It is important to monitor cats for C
      felis infections in northern US states, as geographic distribution of Amblyomma
      americanum expands northward. As free-roaming cats have more contact with the
      tick vectors of C felis, this population allows us to monitor the expansion of C
      felis distribution.

PMID- 28491431
TI  - Hyperinsulinaemic, hypoglycaemic syndrome due to acquired nesidioblastosis in a
      cat.
AB  - Case summary A 6-year-old, neutered female British Shorthair cat presented with
      acute-onset weakness and mental dullness. Initially the cat was mildly
      hyperglycaemic (9.9 mmol/l; reference interval [RI] 3.3-6.7 mmol/l). Over the
      following 12 h the cat developed central blindness, tremors, intermittent
      seizures and opisthotonus. Repeat blood sampling revealed a marked hypoglycaemia
      (0.8 mmol/l). Insulin level (performed on a serum sample collected while the cat
      was hypoglycaemic) was inappropriately elevated (1575 mIU/l; RI 10-80 mIU/l). An
      abdominal ultrasound was unremarkable. An exploratory laparotomy revealed a firm
      and erythematous left limb of the pancreas. Following surgical resection of the
      left limb of the pancreas, the cat returned to a euglycaemic state after a brief
      rebound hyperglycaemia. Histopathology revealed pancreatic fibrosis with marked
      multifocal micronodular hyperplasia of exocrine and endocrine cells.
      Synaptophysin immunohistochemistry confirmed nodular beta-cell hyperplasia.
      Relevance and novel information Nesidioblastosis describes a syndrome of acquired
      hyperinsulinaemia and associated hypoglycaemia secondary to focal or diffuse (non
      neoplastic) beta-cell hyperplasia within the pancreas. Acquired nesidioblastosis
      has been reported in humans, where beta-cell dysregulation is thought to occur in
      response to pancreatic injury. This is the first reported case of clinically
      significant hypoglycaemia due to acquired nesidioblastosis in an adult domestic
      cat. While this condition is rare, nesidioblastosis is being increasingly
      recognised in humans and it is an important differential diagnosis to consider
      when investigating hypoglycaemia as it cannot be distinguished from insulinoma
      without histopathological evaluation. While recurrence has been occasionally
      reported in humans, the prognosis is considered good.

PMID- 28491432
TI  - Renal transitional cell carcinoma with bilateral ocular metastasis in a cat.
AB  - Case summary A 4-year-old, spayed female, domestic shorthair cat was presented
      for evaluation due to a 4 day history of inappetence and lethargy. Physical
      examination revealed mild dehydration and blindness of the left eye. Abnormal
      imaging findings included a well-margined soft tissue mass with irregular central
      cavity located in the dorsal aspect of the caudal lung lobe. Cytological
      examination of the mass revealed chronic inflammation with hemorrhage. Tests for
      parasitic and fungal diseases were negative. Ophthalmic examination 17 days after
      the cat was initially presented revealed severe diffuse pathology of both
      retinas. Left renomegaly was noted 22 days after the initial presentation, and
      cytological examination of samples obtained from the right vitreous, left kidney
      and the pulmonary mass yielded atypical epithelial cells exhibiting malignant
      changes. Post-mortem examination following euthanasia revealed renal transitional
      cell carcinoma with metastasis to both eyes, lungs and skeletal muscle.
      Immunohistochemical evaluation of the neoplastic cells in the eye revealed
      moderate cytoplasmic reactivity for CK7. CK20 immunohistochemistry was negative.
      Relevance and novel information To the best of our knowledge, this is the first
      report of renal transitional cell carcinoma with ocular metastasis in a cat. In
      addition, this report describes immunohistochemistry results of transitional cell
      carcinoma in a cat using CK7 and CK20.

PMID- 28491433
TI  - Evaluation of rapid diagnostic test kits for feline leukemia virus infection
      using samples from naturally infected cats.
AB  - OBJECTIVES: Feline leukemia virus (FeLV) is a potentially life-threatening
      oncogenic retrovirus. The p27 viral core protein is produced by the virus in
      infected feline cells, is found in the cytoplasm in several blood cells and can
      be free in the serum and plasma. ELISA or particle-based immunoassay are commonly
      used to detect the presence of the p27 core protein in samples obtained from
      blood. The objective of this study was to compare the performance of several in
      clinic tests: the SNAP Feline Triple Test (IDEXX Laboratories), the WITNESS FeLV
      FIV Test (Zoetis) and the VetScan Feline FeLV/FIV Rapid Test (Abaxis). METHODS:
      The sample population (100 positive, 105 negative samples) consisted of serum and
      plasma samples submitted to IDEXX's worldwide reference laboratory for feline
      retrovirus testing. Virus isolation and reverse transcriptase PCR results were
      not available and so samples were judged to be positive or negative based on the
      results of the ViraCHEK FeLV (Zoetis) microtiter plate assay. RESULTS: The
      percentage of samples positive and negative for FeLV p27 antigen using the three
      in-clinic tests compared with the ViraCHEK method were as follows: IDEXX Feline
      Triple (positive 98.0%, negative 100%); Zoetis WITNESS (positive 79.0%, negative
      97.1%); Abaxis VetScan (positive 73.0%, negative 97.1%). CONCLUSIONS AND
      RELEVANCE: The SNAP Feline Triple Test demonstrated a high level of agreement for
      FeLV-positive and FeLV-negative samples when assessed in this model. Results of
      FeLV assays can vary among tests.

PMID- 28491434
TI  - Life-threatening haematological complication occurring in a cat after chronic
      carbimazole administration.
AB  - CASE SUMMARY: An 11-year-old spayed female domestic shorthair cat with a history
      of hyperthyroidism treated with carbimazole for 7 months was presented for a
      check-up after a few episodes of vomiting. The cat had been receiving
      prednisolone at 0.5 mg/kg PO q12h for recent pancreatitis and concurrent
      inflammation of liver and small intestines confirmed by biopsies. Clinical
      examination revealed pale mucous membranes with a capillary refill time of <2 s.
      Haematology showed severely decreased packed cell volume (16%), and increased
      prothrombin time (42 s), partial thromboplastin time (>120 s) and fibrinogen
      serum concentration (3.5 g/l). Morphological changes of thrombocytes in the
      absence of thrombocytopenia were also noted. In-saline agglutination test was
      positive. Abdominal radiographic and ultrasonographic examinations excluded the
      presence of organ abnormalities and peritoneal effusion. Blood biochemistry was
      unremarkable. Feline leukaemia virus and feline immunodeficiency virus tests were
      negative. On the basis of these findings, immune-mediated anaemia secondary to
      chronic carbimazole administration was suspected. Prednisolone was increased to 2
      mg/kg PO q24h and carbimazole tablets were stopped. Despite close monitoring and
      intensive care, the cat died the same evening of admission to the hospital.
      RELEVANCE AND NOVEL INFORMATION: This report suggests that severe haemotoxicity
      may occur as a sequel of chronic carbimazole administration in cats. Routine
      bloodwork and accurate follow-up of cats under treatment with thyrotoxic therapy
      may be advisable, in order to detect haematological changes before lethal
      complications occur.

PMID- 28491435
TI  - Scapular osteomyelitis in an immature domestic shorthair cat.
AB  - CASE SUMMARY: A 12-week-old, male, domestic shorthair cat was presented with
      severe left thoracic limb lameness. Investigation included physical examination,
      diagnostic imaging with radiography and CT, histopathology and microbiological
      culture. Physical examination revealed a large, firm mass on the left scapula.
      Radiography and CT showed a monostotic spherical expansile bone lesion in the
      infraspinatus fossa of the left scapula. The histopathological description was a
      central acute suppurative osteomyelitis with reactive fibrosis and new bone
      formation at the periphery. Aerobic and anaerobic cultures were negative and the
      underlying cause of the osteomyelitis could not be identified. The use of broad
      spectrum antibiotics for 8 weeks proved effective with full clinical recovery and
      no signs of relapse during the follow-up time of 8 months. RELEVANCE AND NOVEL
      INFORMATION: This report describes the management and outcome of a rare case of
      osteomyelitis with severe deformation of scapular bone morphology in an immature
      cat that was treated successfully with full recovery of limb function and
      restored integrity of the scapula.

PMID- 28491436
TI  - Primary bronchial carcinoma associated with bone marrow metastasis and
      paraneoplastic monoclonal gammopathy in a cat.
AB  - CASE SUMMARY: Herein we describe an unusual metastatic pattern and paraneoplastic
      manifestation of a bronchial carcinoma in a cat. An 8 year-old cat presented with
      a diminished appetite, dysphagia, weight loss, lethargy and coughing. Thoracic
      radiographs revealed a lung mass. Bronchial carcinoma was diagnosed on the basis
      of histology and was associated with a lymphoplasmocytic infiltration of the
      fibrovascular stroma. Biochemistry showed hyperproteinaemia. Serum protein
      electrophoresis showed a narrow spike in the gamma region. Bone marrow cytology
      revealed an infiltrate with numerous clustered epithelial cells. The cat was
      euthanased 2 months later because of anorexia and poor general condition.
      RELEVANCE AND NOVEL INFORMATION: To the best of our knowledge, this is the first
      clinical description of primary bronchial carcinoma associated with bone marrow
      metastases and paraneoplastic monoclonal gammopathy in a cat.

PMID- 28491437
TI  - Hypersensitivity reaction associated with subcutaneous glargine insulin therapy
      in a cat.
AB  - CASE SUMMARY: A 14-year-old, domestic shorthair cat was treated for transient
      diabetes mellitus for 3 months with glargine insulin, which was discontinued when
      the diabetes mellitus resolved. Approximately 36 months later the diabetes
      mellitus recurred and glargine insulin was restarted. Within 2-3 mins of the
      first injection the cat collapsed, developed profuse vomiting and diarrhea, as
      well as facial swelling and diffuse erythema. A hypersensitivity reaction was
      suspected and the cat was treated with antihistamines, aggressive fluid therapy
      and gastrointestinal support. The cat made a full recovery and was discharged 3
      days later. Six months later the cat re-presented for relapse of its diabetes
      mellitus and an intradermal skin challenge with 1:20 diluted insulin was
      performed confirming a hypersensitivity to glargine. The cat continues to be well
      regulated on porcine zinc insulin without any hypersensitivity reactions noted.
      RELEVANCE AND NOVEL INFORMATION: Hypersensitivity reactions to insulin
      administration are rarely described in human medicine. This is the first reported
      case of a hypersensitivity reaction secondary to glargine insulin in a cat.
      Clinicians should be aware of this potential complication, particularly in
      animals with a previous history of insulin administration and the potential to
      utilize intradermal testing with insulin.

PMID- 28491438
TI  - Isolated unilateral absence of the right pulmonary artery in two cats visualized
      by computed tomography angiography.
AB  - CASE SERIES SUMMARY: Two cats were evaluated for progressive exercise
      intolerance, dyspnea and unilateral infiltrate of the left lung. Computed
      tomography angiography (CTA) revealed absence of the right pulmonary artery in
      both cats with systemic arterial collateral vessels perfusing the right segmental
      pulmonary arteries. In one case, the collateral vessels arose from the esophageal
      artery, while in the other case they derived off the right costocervical trunk.
      One cat was diagnosed with pulmonary hypertension and was euthanized owing to
      progressive respiratory distress despite medical management with sildenafil,
      pimobendan, clopidogrel and furosemide. The other cat, without echocardiographic
      evidence of pulmonary hypertension, was successfully managed with furosemide and
      enalapril for more than 4 years. RELEVANCE AND NOVEL INFORMATION: CTA allowed
      visualization of a rare congenital heart malformation, unilateral absence of the
      right pulmonary artery, in two cats and accurately characterized the source of
      collateral blood supply to the affected lung. Severe pulmonary hypertension may
      be a negative prognostic factor in cats with this condition as medical therapy in
      the cat without evidence of pulmonary hypertension resolved clinical signs, while
      the cat with severe pulmonary hypertension died from the disease.

PMID- 28491439
TI  - Mycobacterial panniculitis caused by Mycobacterium thermoresistibile in a cat.
AB  - CASE SUMMARY: A domestic shorthair cat was evaluated for chronic, bilateral,
      ulcerative dermatitis affecting the inguinal region and lateral aspects of both
      pelvic limbs. Histopathologic examination of skin biopsies collected throughout
      the course of disease revealed chronic pyogranulomatous ulcerative dermatitis.
      Aerobic bacterial skin cultures yielded growth of a methicillin-resistant
      Staphylococcus aureus and Corynebacterium amycolatum. Upon referral the clinical
      findings were suggestive of a non-tuberculous Mycobacterium species infection.
      Previously obtained skin cultures failed to yield growth of mycobacterial
      organisms. A deep skin biopsy was collected and submitted for mycobacterial
      culture. At 5 weeks of incubation Mycobacterium thermoresistibile was isolated.
      In previous reports, M thermoresistibile has been isolated after 2-4 days of
      incubation, suggesting that this strain may have been a slower growing variant,
      or other factors (such as prior antimicrobial therapy) inhibited rapid growth of
      this isolate. The cat was hospitalized for intravenous antibiotic therapy,
      surgical debridement of wounds, vacuum-assisted wound closure therapy and
      reconstruction procedures. The wounds were ultimately primarily closed and the
      cat was discharged to the owner after 50 days of hospitalization. Seven months
      after hospitalization, the ulcerative skin lesions had healed. RELEVANCE AND
      NOVEL INFORMATION: To our knowledge, only two cases of M thermoresistibile
      panniculitis have been reported in cats. In the only detailed report of feline M
      thermoresistibile panniculitis, treatment was not attempted. The second case only
      reported detection of M thermoresistibile by PCR without a clinical description
      of the case. In our case report, severe chronic skin infection with M
      thermoresistibile was addressed using prolonged specific antibiotic therapy,
      surgical debridement and reconstructions, and treatment of secondary bacterial
      infections.

PMID- 28491440
TI  - Marginal resection and adjuvant strontium plesiotherapy in the management of
      feline eyelid malignant peripheral nerve sheath tumours: two cases.
AB  - CASE SERIES SUMMARY: Two cats with a marginally resected eyelid malignant
      peripheral nerve sheath tumour were treated with adjuvant strontium plesiotherapy
      a few weeks after surgery. The dose applied in both cases was 200 Gy to the
      surface, in five fractions, on a Monday-Wednesday-Friday basis. The treatment
      aimed to achieve a clinical margin of approximately 1 cm around the surgical scar
      and multiple application fields were required to cover such an area. Local
      recurrence was not seen in either case after 1330 and 645 days, respectively.
      RELEVANCE AND NOVEL INFORMATION: The majority of periocular malignant peripheral
      nerve sheath tumours reported in the literature recur after surgery. In the two
      cases described in this report the combination of surgery and adjuvant
      plesiotherapy has been able to provide good local control with minimal toxicity.
      This multimodal approach could be considered as an alternative to aggressive
      surgery such as enucleation or exenteration.

PMID- 28491441
TI  - Successful treatment of vaginal malakoplakia in a young cat.
AB  - CASE SUMMARY: A 3-year-old, female, spayed, domestic shorthair cat presented for
      dysuria and haematuria, unresponsive to antibiotic treatment. A small, fleshy,
      erythematous mass protruded from the vaginal vault. Ultrasound identified a
      vaginal mass effect with mixed echogenicity measuring in excess of 3 cm.
      Vaginoscopy confirmed an extensive, fleshy, irregular mass that was characterised
      histologically as pyogranulomatous vaginitis, with periodic acid-Schiff-positive
      macrophages containing gram-negative bacteria. Fluorescence in situ hybridisation
      analysis demonstrated invasive intracellular Escherichia coli. Vaginal
      malakoplakia was diagnosed. Tissue culture and antimicrobial susceptibility of E
      coli was used to guide treatment. A 6 week course of enrofloxacin 5 mg/kg q24h
      resulted in complete resolution of the mass and clinical signs. RELEVANCE AND
      NOVEL INFORMATION: Malakoplakia is a rare chronic inflammatory condition that has
      been previously reported in the bladder of two cats. The pathogenesis of
      malakoplakia is thought to involve ineffective killing of bacteria (eg. E coli),
      similar to granulomatous colitis in Boxers and French Bulldogs. The literature on
      malakoplakia in cats is sparse. This is the first reported feline case with
      vaginal involvement, intracellular E coli and successful treatment with a
      fluoroquinolone. Malakoplakia is an important, non-neoplastic differential
      diagnosis when a mass is identified in the urogenital system of a young cat.

PMID- 28491442
TI  - Respiratory distress associated with lungworm infection in a kitten.
AB  - CASE SUMMARY: A 5-month-old feral kitten developed worsening respiratory signs,
      including tachypnea, coughing and wheezing after standard anthelmintic treatment
      with fenbendazole at a local shelter. The kitten was referred to the University
      of California, Davis, William R Pritchard Veterinary Medicine Teaching Hospital
      for further evaluation. Thoracic radiographs revealed a severe diffuse
      bronchointerstitial pattern with bronchial cuffing, ill-defined nodules and
      lymphadenomegaly. Differentials included infectious etiologies such as
      toxoplasmosis, feline infectious peritonitis and cryptococcosis. Parasitic
      infection was considered less likely, owing to previous anthelmintic treatment.
      Bronchoalveolar lavage revealed marked neutrophilic and eosinophilic
      inflammation, and parasitic larvae were observed in a swab of trachea mucus. PCR
      confirmed the larvae as Aelurostrongylus abstrusus. The kitten recovered with two
      more rounds of anthelmintic treatment. RELEVANCE AND NOVEL INFORMATION: Parasitic
      pneumonia should be considered as a cause of respiratory distress in kittens and
      cats. Lungworm infections have been more commonly reported in free-roaming young
      and adult cats, but cannot be excluded as a differential diagnosis in cats from
      varied environments and in kittens. Kittens appear to be especially sensitive to
      lungworm infections, manifested by the development of more severe clinical signs;
      thus lungworm infection should always be considered when presented with a kitten
      in respiratory distress. In the absence of cytologic confirmation of infection
      via bronchoalveolar lavage or oropharyngeal swab, PCR provides a valuable means
      for identification of lungworms, such as A abstrusus and Troglostrongylus
      brevior.

PMID- 28491443
TI  - CT findings in two cats with broncholithiasis.
AB  - CASE SERIES SUMMARY: Chronic inflammatory airway disease with secondary
      broncholithiasis was diagnosed in two cats from CT and bronchoalveolar lavage
      cytological findings. In one cat with progressively worsening lower respiratory
      tract signs, more than 80 discrete, highly attenuating endobronchial opacities
      were detected on thoracic CT. The broncholiths were distributed throughout the
      right middle, and left and right caudal lung lobes, and the caudal part of the
      left cranial and accessory lobes. In the other cat broncholithiasis was an
      incidental finding on thoracic radiographs taken during diagnostic investigation
      of inappetence. On thoracic CT, 25 calcified endobronchial opacities were
      detected in the left caudal lung lobe in secondary and tertiary bronchi. CT
      features of chronic inflammatory airway disease were present in both cases,
      including bronchiectasis, atelectasis, flattening of the diaphragm and bronchial
      wall thickening. RELEVANCE AND NOVEL INFORMATION: This is the first report to
      document CT features of broncholithiasis in cats. Feline broncholithiasis should
      be considered as a differential diagnosis in any case where calcified
      endobronchial material is evident on thoracic radiographs or CT.

PMID- 28491444
TI  - Cerebral pyogranulomatous encephalitis caused by Cladophialophora bantiana in a
      15-week-old domestic shorthair kitten.
AB  - CASE SUMMARY: A case of cerebral phaeohyphomycosis caused by Cladophialophora
      bantiana is described in a 15-week-old domestic shorthair kitten. RELEVANCE AND
      NOVEL INFORMATION: Cerebral phaeohyphomycosis is a rare condition in cats caused
      by dematiaceous fungi. This report describes the clinical and histopathological
      findings in the youngest case documented in a feline, provides a brief review of
      aetiology, diagnosis, treatment and prognosis of cerebral phaeohyphomycosis and
      demonstrates the importance of molecular diagnostics in accurate mycotic species
      identification.

PMID- 28491445
TI  - Primary adrenal lymphoma causing hypoaldosteronism in a cat.
AB  - CASE SUMMARY: A 10-year-old, 5.1 kg (11.2 lb), male castrated cat was presented
      with signs of lethargy and decreased appetite at home after being previously
      healthy. Serum biochemical analysis identified normokalemia (5.1 mmol/l;
      reference interval [RI] 3.4-5.6 mmol/l) and severe hyponatremia (123 mmol/l; RI
      145-158 mmol/l), with an Na/K ratio of 24 (RI 32-41). Baseline serum cortisol was
      low to normal, but serum aldosterone was markedly decreased with a pre
      adrenocorticotropic hormone stimulation concentration of 13 pmol/l (RI 194-388
      pmol/l) and post-adrenocorticotropic hormone stimulation concentration of 21
      pmol/l (RI 277-721 pmol/l). Hematologic and biochemical analyses were otherwise
      unremarkable. Abdominal ultrasound revealed bilaterally enlarged adrenal glands
      with no other abnormalities noted; thoracic radiographs also did not identify any
      signs of metastasis. Fine-needle aspiration was strongly suggestive of lymphoma
      of the adrenal glands, and PCR for antigen receptor rearrangement was positive
      for B-cell clonal expansion; based on these findings, a diagnosis of primary
      adrenal B-cell lymphoma was made. Stable disease was achieved for a short period
      of time following vincristine, cyclophosphamide, prednisolone and fludrocortisone
      therapy, followed by progressive adrenal enlargement and electrolyte derangements
      that responded to neither doxorubicin nor adjustments in fludrocortisone dosage.
      Ultrasonographic metastasis was not identified at any time, and other organ
      derangements were not noted on hematologic or biochemical analyses. The cat was
      euthanized 55 days after initial presentation. RELEVANCE AND NOVEL INFORMATION:
      This is the first report of primary adrenal lymphoma in a cat, with presenting
      signs compatible with hypoaldosteronism. Lymphoma should be a differential for
      cats presenting with adrenal enlargement or clinical signs and biochemical
      changes consistent with hypoaldosteronism or hypoadrenocorticism.

PMID- 28491446
TI  - Severe muscle fasciculations and tremor in a cat with hypochloraemic metabolic
      alkalosis secondary to duodenal obstruction.
AB  - CASE SUMMARY: An 18-month-old, female spayed, Australian Mist cat presented with
      a 24 h history of muscle tremors and inappetence progressing to collapse with
      generalised muscle fasciculations. The cat was diagnosed with a hypochloraemic
      metabolic alkalosis due to a duodenal foreign body found to be a trichobezoar at
      coeliotomy. The cat made a complete recovery after enterotomy to remove the
      trichobezoar, with cessation of neuromuscular clinical signs and normalisation of
      its electrolyte and acid-base imbalances. RELEVANCE AND NOVEL INFORMATION: Muscle
      fasciculations and tremors in cats can be caused by intoxications, metabolic
      derangements, encephalomyelitis, feline hyperaesthesia syndrome and cerebellar
      diseases. The presenting clinical signs of severe muscle fasciculations and
      tremors have not previously been reported in association with an intestinal
      obstruction in the cat.

PMID- 28491447
TI  - Successful treatment of multifocal pedal Prototheca wickerhamii infection in a
      feline immunodeficiency virus-positive cat with multiple Bowenoid in situ
      carcinomas containing papillomaviral DNA sequences.
AB  - CASE SUMMARY: A 16-year-old, castrated male, feline immunodeficiency virus (FIV)
      positive, domestic shorthair cat developed multiple skin lesions. Most of these
      were Bowenoid carcinoma in situ and contained DNA sequences consistent with Felis
      catus papillomavirus type 2. Two additional lesions that developed in the skin
      and subcutaneous tissues between the digital and carpal pads on the left forelimb
      and right hindlimb were shown by cytology, histology and culture to be caused by
      Prototheca wickerhamii. These lesions failed to improve in response to systemic
      therapy treatment with itraconazole, but excision by sharp en bloc resection with
      follow-up oral itraconazole therapy proved curative for one lesion, although the
      other lesion recurred, necessitating a second surgery. RELEVANCE AND NOVEL
      INFORMATION: This is only the second reported case of feline protothecosis from
      Australia and the first case that has been cultured and identified to the species
      level. Also of great interest was the presence of multiple papillomavirus
      associated neoplastic lesions, which may have afforded a portal of entry for the
      algal pathogen and the cat's positive FIV status; the latter might have impacted
      on both viral and algal pathogenesis by effects on immunocompetence.

PMID- 28491448
TI  - Multimodal non-surgical treatment of a feline tracheal adenocarcinoma.
AB  - CASE SUMMARY: A 10-year-old, castrated male domestic shorthair cat presented with
      a 2-3 month history of weight loss, lethargy and coughing. Thoracic radiographs
      revealed a soft tissue opacity overlying the dorsal trachea from the first rib to
      second rib and the ventral aspect of the trachea extending from the second rib to
      approximately the fourth rib. CT confirmed a mass involving the dorsal, right
      lateral and ventral aspects of the trachea narrowing the lumen and extending from
      vertebra C7 through T4. Bronchoscopy revealed a partially circumferential
      irregular and multilobulated tracheal mass, which was biopsied. The
      histopathological diagnosis was tracheal adenocarcinoma. The cat was treated with
      a definitive course of external beam radiation therapy (RT; 3 Gy * 18), cytotoxic
      chemotherapy, a tyrosine kinase inhibitor and palliative RT. The cat remained
      asymptomatic for 2 months and the mass remained stable radiographically for 11
      months after RT. RELEVANCE AND NOVEL INFORMATION: With multimodal treatment the
      cat had a survival time of 755 days. Initial treatment included definitive RT,
      carboplatin and piroxicam, followed by toceranib phosphate and palliative RT when
      the mass recurred. This case report describes the first documented use of non
      surgical treatment and long-term outcome of tracheal adenocarcinoma in a cat.
      This case report is an indication that prolonged survival can be achieved with
      multimodal therapy.

PMID- 28491449
TI  - Metastatic pulmonary carcinomas in cats ('feline lung-digit syndrome'): further
      variations on a theme.
AB  - CASE SERIES SUMMARY: The aim of this retrospective case series was to describe
      seven cases where cats with primary lung tumours were presented because of
      metastases to extra-pulmonary sites ('feline lung-digit syndrome'). Specifically,
      we wanted to emphasise less typical case descriptions where tumour emboli
      resulted in lesions developing in the musculature (including the muscles of the
      head), skin or distal aorta. RELEVANCE AND NOVEL INFORMATION: The cases are
      presented to increase clinical awareness of this entity in feline practice,
      especially when characteristic combinations of clinical signs are present. When
      clinicians have a high index of suspicion for these presentations, radiology
      (thorax and digits) or ultrasound (distal aorta), combined with collection of
      fine needle aspirate specimens for cytology, are usually sufficient to secure a
      definitive diagnosis. Novel information in this series includes CT and MRI
      findings from some cases. Typically, needle aspiration or biopsy targeting the
      skin, digits and lesions in musculature is far easier compared with sampling the
      primary tumour site in the lungs. The differential diagnosis and investigation of
      multiple digital lesions is also considered.

PMID- 28491452
TI  - Renal oncocytoma in a cat with chronic renal failure.
AB  - CASE SUMMARY: A 9-year-old male neutered domestic shorthair cat presented with
      anorexia. Ultrasonography showed an irregularly shaped hypoechoic mass in the
      cranial pole of the right kidney. Ultrasound-guided fine-needle aspiration of the
      renal mass was performed. Cytology revealed moderate cellularity smears composed
      of epithelial cell clusters, which consisted of an exclusive population of
      oncocytic cells seen in sheets and papillary clusters along with abundant single
      cells. A moderate-to-abundant amount of densely stained granular cytoplasm with
      round nuclei and indistinct nucleoli was seen. The cytological diagnosis was
      renal oncocytic neoplasm. CT and surgical resection revealed a firm tan mass in
      the right kidney. A final diagnosis of renal oncocytoma was made on the basis of
      histology, immunohistochemical staining profile (positive for cytokeratin, and
      negative for chromogranin A, neuron-specific enolase and vimentin) of neoplastic
      cells, together with the electronic microscopy results. RELEVANCE AND NOVEL
      INFORMATION: We believe that this is the first report of the cytological features
      of feline renal oncocytoma.

PMID- 28491450
TI  - Contribution of oral triamcinolone to treating proliferative and necrotising
      otitis externa in a 14-year-old Persian cat.
AB  - CASE SUMMARY: A 14-year-old female spayed cat was referred for recurrent otitis
      externa and unusual proliferative lesions in both ear canals. The affected pinnae
      and external ear canals were covered with large reddish-to-dark-brown verrucous
      and necrotic tissue. Friable material and exudates occluded both ear canals.
      Proliferative lesions developed in both ears 2-3 weeks before referral. The
      histopathological diagnosis from two biopsies obtained from the friable materials
      with endoscopic biopsy forceps was proliferative and necrotising otitis externa
      (PNOE). Treatment was initiated with once-daily application of a potent topical
      glucocorticoid (mometasone furoate) to both ears. Although the auricle and
      vertical ear canals responded well, no improvement was seen in the horizontal
      part of the ear canal after 9 weeks. Therefore, oral triamcinolone (0.9 mg/kg
      q24h) was added for 1 week, and was then tapered (q48h) for 3 weeks. Most lesions
      resolved, and after a further 2 weeks of prednisolone (2 mg/kg q48h) there was
      complete resolution. No recurrence was observed during a 2 year follow-up period.
      RELEVANCE AND NOVEL INFORMATION: PNOE commonly occurs in kittens, but it can
      develop in older cats. To our knowledge, the PNOE in this case is the oldest age
      of onset reported. This condition is rare and was only described recently, and
      therapeutic options appear limited. According to previously published reports,
      steroid therapy is ineffective, and tacrolimus is the only treatment known to
      achieve resolution. However, oral and topical glucocorticoids were beneficial in
      this case.

PMID- 28491453
TI  - Surgical management of medial humeral epicondylitis, cubital synovial
      osteochondromatosis and humeroradial subluxation in a cat.
AB  - CASE SUMMARY: A 13-year-old domestic shorthair cat presented for evaluation of
      pain and difficulty ambulating. Orthopedic examination and CT facilitated a
      diagnosis of bilateral elbow synovial osteochondromatosis with medial humeral
      epicondylitis and concurrent osteoarthritis. Right humeroradial subluxation was
      evident on CT images, but no instability was evident preoperatively. Surgical
      treatment was elected, including external neurolysis of the ulnar nerve, removal
      of the areas of mineralization within the flexor carpi ulnaris muscle and medial
      arthrotomy to remove intra-articular mineralized bodies. Following closure,
      instability of the right elbow was noted with humeroradial subluxation
      necessitating placement of circumferential suture prostheses to provide
      satisfactory stability. Reassessment was performed 2, 6, 12, 24 and 40 weeks
      postoperatively and revealed maintenance of elbow stability and substantial
      improvement in mobility and comfort. RELEVANCE AND NOVEL INFORMATION: While
      humeroradial subluxation has been reported in association with medial humeral
      epicondylitis on post-mortem examination, associated clinically significant
      instability has not been documented previously. Surgeons should be aware of the
      potential for this complication and check elbow stability following surgery.
      Despite this complication, a favorable medium-term outcome was achieved for this
      cat.

PMID- 28491454
TI  - Crossed fused renal ectopia in a Persian cat.
AB  - CASE SUMMARY: This report describes a rare case of crossed fused renal ectopia
      (CFRE) in a cat. A mature intact male Persian cat presented with bloody nasal
      discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused
      with an orthotopic right kidney and a concurrent feline infectious peritonitis
      (FIP) infection. The FIP was responsible for clinical signs in this cat, while
      clinical signs associated with CFRE were not obvious. Despite receiving intensive
      treatment, the cat died. A post-mortem examination was not performed because the
      owners declined approval. RELEVANCE AND NOVEL INFORMATION: To the best of our
      knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this
      report describes the CT features of L-shaped CFRE in a cat.

PMID- 28491456
TI  - JFMS Open Reports: new look, new 'Collections'.

PMID- 28491455
TI  - Use of adjunctive prednisolone in the management of a cat with bilateral
      quadriceps contracture following trauma.
AB  - CASE SUMMARY: A 6-month-old cat was successfully treated for bilateral quadriceps
      contracture. Conventional treatments including surgery, dynamic flexion apparatus
      and physical therapy along with analgesics and non-steroidal anti-inflammatory
      drugs resulted in temporary clinical improvement that was relapsing. The
      initiation of supplementary corticosteroid treatment with prednisolone coincided
      with an immediate and sustained clinical improvement and long-term resolution.
      RELEVANCE AND NOVEL INFORMATION: Successful treatment of bilateral quadriceps
      contracture has not previously been reported in a cat. Quadriceps contracture
      remains a challenging condition to treat with some cases unresponsive to therapy.
      Systemic prednisolone treatment appeared to be of benefit in the management of
      this case and may have a role in some cats where muscle contracture appears
      relapsing in nature. Further prospective investigations in cats with muscle
      contracture, including muscle biopsies of affected cats, are warranted.

PMID- 28491457
TI  - A case of acute acquired obstructive hydrocephalus in a cat with suspected
      ischaemic cerebellar infarct.
AB  - CASE SUMMARY: A case of acquired acute obstructive hydrocephalus that developed
      as a complication of an ischaemic infarct in the vascular territory of the
      rostral cerebellar artery is described in an adult domestic shorthair cat. The
      clinical findings, diagnostic investigations, treatment and prognosis are
      reported. MRI findings are described in detail. RELEVANCE AND NOVEL INFORMATION:
      This is the first report of obstructive hydrocephalus as a complication of an
      ischaemic infarct in the region of the rostral cerebellar artery in a cat. MRI
      findings are described in detail with regard to the recognition of the early
      signs of obstructive hydrocephalus. A brief review of the literature is included,
      as this complication has been frequently reported in humans.

PMID- 28491458
TI  - Caecocolic intussusception associated with a caecal polyp and concurrent
      hepatocellular carcinoma in a cat.
AB  - CASE SUMMARY: A 17-year-old female neutered domestic shorthair cat presented for
      several days of reduced faecal volume and a rectal prolapse. Physical examination
      revealed a 2 cm rectal prolapse, hepatomegaly and a low body condition score of
      3/9. Haematology and biochemistry revealed a mild non-regenerative anaemia
      (haematocrit 24.5%; reference interval [RI] 30.3-52.3%), a mild mature
      neutrophilia (16.21 * 109/l; RI 1.48-10.29 * 109/l) and a mild increase in
      alanine aminotransferase activity (222 IU/l; RI 12-130 IU/l). Abdominal
      radiographs identified hepatomegaly. The rectal prolapse was reduced under
      general anaesthesia. Abdominal ultrasound identified a caecocolic intussusception
      and a large hepatic mass. Thoracic radiographs were unremarkable. Hepatic fine
      needle aspirate cytology revealed well-differentiated hepatocytes. A typhlectomy
      was performed and the quadrate liver lobe, with mass, was resected. Gross
      examination of the caecum identified a focal polyp; histopathology showed
      moderate plasmacytic-lymphocytic typhlitis and reactive mucosal-associated
      lymphoid tissue. The hepatic mass was diagnosed as a well-differentiated
      hepatocellular carcinoma. Six weeks postoperatively the cat had gained 0.5 kg,
      had an improved body condition score of 5/9 and resolution of clinical signs. The
      cat died acutely 1 year later from an unknown cause. RELEVANCE AND NOVEL
      INFORMATION: Caecocolic intussusception is rare in cats and uncommon in dogs.
      This is the third report in a cat and the first associated with a caecal polyp.
      As reported in dogs, the outcome following surgery was good. Hepatocellular
      carcinoma is a rarely reported feline neoplasm, which may have a good prognosis
      with surgical resection.

PMID- 28491459
TI  - On Your Feet to Earn Your Seat: pilot RCT of a theory-based sedentary behaviour
      reduction intervention for older adults.
AB  - BACKGROUND: Of all age groups, older adults spend most of the time sitting and
      are least physically active. This sequential, mixed-methods feasibility study
      used a randomised controlled trial design to assess methods for trialling a habit
      based intervention to displace older adults' sedentary behaviour with light
      activity and explore impact on behavioural outcomes. METHODS: Eligibility
      criteria were age 60-74 years, retired, and >=6 h/day leisure sitting. Data were
      collected across four sites in England. The intervention comprised a booklet
      outlining 15 'tips' for disrupting sedentary habits and integrating activity
      habits into normally inactive settings, and eight weekly self-monitoring sheets.
      The control was a non-habit-based factsheet promoting activity and sedentary
      reduction. A computer-generated 1:1 block-randomisation schedule was used, with
      participants blinded to allocation. Participants self-reported sedentary
      behaviour (two indices), sedentary habit, physical activity (walking, moderate,
      vigorous activity) and activity habit, at pre-treatment baseline, 8- and 12-week
      follow-ups and were interviewed at 12 weeks. Primary feasibility outcomes were
      attrition, adverse events and intervention adherence. The secondary outcome was
      behavioural change. RESULTS: Of 104 participants consented, 103 were randomised
      (intervention N = 52, control N = 51). Of 98 receiving allocated treatment, 91
      (93%; intervention N = 45; control N = 46) completed the trial. One related
      adverse event was reported in the intervention group. Mean per-tip adherence
      across 7 weeks was >=50% for 9/15 tips. Qualitative data suggested acceptability
      of procedures, and, particularly among intervention recipients, the allocated
      treatment. Both groups appeared to reduce sedentary behaviour and increase their
      physical activity, but there were no apparent differences between groups in the
      extent of change. CONCLUSIONS: Trial methods were acceptable and feasible, but
      the intervention conferred no apparent advantage over control, though it was not
      trialled among the most sedentary and inactive population for whom it was
      developed. Further development of the intervention may be necessary prior to a
      large-scale definitive trial. One possible refinement would combine elements of
      the intervention with an informational approach to enhance effectiveness. TRIAL
      REGISTRATION: ISRCTN47901994 (registration date: 16th January 2014; trial end
      date 30th April 2015).

PMID- 28491460
TI  - Correlation between retinal function and microstructural foveal changes in
      intermediate age related macular degeneration.
AB  - PURPOSE: To assess foveal microstructural changes influencing retinal sensitivity
      (RS) and fixation stability using microperimeter MP-1 in intermediate age-related
      macular degeneration (AMD). METHODS: In this cross-sectional study, 22 eyes of 22
      patients (mean age: 75 +/- 9.02 years) with intermediate AMD were enrolled.
      Retinal sensitivity and bivariate contour ellipse area (BCEA) were obtained by
      microperimetry MP-1 (Humphrey 10-2 68-loci grid) under mesopic conditions. Drusen
      type, drusenoid pigment epithelial detachment, hyperreflective foci (HF),
      integrity of external limiting membrane (ELM), inner ellipsoid zone (ISel),
      RPE/Bruch's membrane complex (RPE/B) and subfoveal choroidal thickness were
      analyzed in the foveal region and compared with RS and BCEA. Spearman's rank
      correlation coefficient was used to evaluate the relationship between variables.
      Logistic regression analysis was also used to assess morphological predictor
      influencing RS or BCEA. RESULTS: RS was strongly and inversely related with the
      presence of HF (r = -0.66, P = 0.001), integrity of ELM (r = -0.70, P < 0.001),
      ellipsoid zone (r = -0.45, P = 0.03). Instead, BCEA is positively related to the
      ellipsoid zone integrity (r = 0.45, P = 0.03). Logistic regression analysis
      confirmed that disruption of ISel influenced fixation stability (ExpB: 9.69, P =
      0.04) but not RS. Instead, the presence of HF and disruption of ELM predicted RS
      reduction (ExpB: 0.55, P = 0.02 and ExpB: 0.29, P = 0.04, respectively).
      CONCLUSIONS: The integrity of ELM and the presence of HF are both predictors of
      RS. The ELM status may be considered a new biomarker of retinal function together
      with HF. Instead, the integrity of ISel band seems to be a more selective
      predictor of BCEA than RS.

PMID- 28491461
TI  - Imaging findings of solitary uterine granulocytic sarcoma.
AB  - A 29-year old woman with a history of vaginal bleeding was referred to our
      hospital. Transvaginal ultrasonography revealed a hypervascular cervical mass and
      malignancy was suspected. Computed tomography (CT), magnetic resonance imaging,
      and 18-F-fluorodeoxyglucose positron emission tomography/CT were performed. She
      was finally diagnosed with granulocytic sarcoma based on pathological
      examination.

PMID- 28491462
TI  - Understanding microstructure of the brain by comparison of neurite orientation
      dispersion and density imaging (NODDI) with transparent mouse brain.
AB  - BACKGROUND: Neurite orientation dispersion and density imaging (NODDI) is a
      diffusion magnetic resonance imaging (MRI) technique with the potential to
      visualize the microstructure of the brain. Revolutionary histological methods to
      render the mouse brain transparent have recently been developed, but verification
      of NODDI by these methods has not been reported. PURPOSE: To confirm the
      concordance of NODDI with histology in terms of density and orientation
      dispersion of neurites of the brain. MATERIAL AND METHODS: Whole brain diffusion
      MRI of a thy-1 yellow fluorescent protein mouse was acquired with a 7-T MRI
      scanner, after which transparent brain sections were created from the same mouse.
      NODDI parameters calculated from the MR images, including the intracellular
      volume fraction (Vic) and the orientation dispersion index (ODI), were compared
      with histological findings. Neurite density, Vic, and ODI were compared between
      areas of the anterior commissure and the hippocampus containing crossing fibers
      (crossing areas) and parallel fibers (parallel areas), and the correlation
      between fiber density and Vic was assessed. RESULTS: The ODI was significantly
      higher in the crossing area compared to the parallel area in both the anterior
      commissure and the hippocampus (P = 0.0247, P = 0.00022, respectively). Neurite
      density showed a similar tendency, but was significantly different only in the
      hippocampus (P = 7.91E-07). There was no significant correlation between neurite
      density and Vic. CONCLUSION: NODDI was verified by histology for quantification
      of the orientation dispersion of neurites. These results indicate that the ODI is
      a suitable index for understanding the microstructure of the brain in vivo.

PMID- 28491463
TI  - "Pro-dopamine regulation (KB220ZTM)" as a long-term therapeutic modality to
      overcome reduced resting state dopamine tone in opiate/opioid epidemic in
      America.
AB  - Since it is known that relapse, morality, and hospitalizations have been tied to
      the presence of the Dopamine D2 Receptor A1 allele, as one example, and carriers
      of this gene variant have a proclivity to favor amino-acid therapy, it seems
      intuitive that the incorporation of modalities to provide a balance and or
      restoration of hypodopaminergia should be considered as a front-line tactic to
      overcome the current American opiate/opioid epidemic, saving millions from death
      and unwanted locked-in-addiction. If we continue down the prim road path of
      fighting addiction to narcotics with narcotics, we are doomed to fail. This
      lesson can also have global interest.

PMID- 28491464
TI  - Decreasing Aerosol Loading in the North American Monsoon Region.
AB  - We examine the spatio-temporal variability of aerosol loading in the recent
      decade (2005-2014) over the North American Monsoon (NAM) region. Emerging
      patterns are characterized using aerosol optical depth (AOD) retrievals from the
      NASA Terra/Moderate Resolution Imaging Spectroradiometer (MODIS) instrument along
      with a suite of satellite retrievals of atmospheric and land-surface properties.
      We selected 20 aerosol hotspots and classified them into fire, anthropogenic,
      dust, and NAM alley clusters based on the dominant driver influencing aerosol
      variability. We then analyzed multivariate statistics of associated anomalies
      during pre-, monsoon, and post-monsoon periods. Our results show a decrease in
      aerosol loading for the entire NAM region, confirming previous reports of a
      declining AOD trend over the continental United States. This is evident during
      pre-monsoon and monsoon for fire and anthropogenic clusters, which are associated
      with a decrease in the lower and upper quartile of fire counts and carbon
      monoxide, respectively. The overall pattern is obfuscated in the NAM alley,
      especially during monsoon and post-monsoon seasons. While the NAM alley is mostly
      affected by monsoon precipitation, the frequent occurrence of dust storms in the
      area modulates this trend. We find that aerosol loading in the dust cluster is
      associated with observed vegetation index and has only slightly decreased in the
      recent decade.

PMID- 28491465
TI  - The potential scientist's dilemma: How the Masculinization of Science Shapes
      Friendships and Science Job Preferences.
AB  - In the United States, girls and boys have similar science achievement, yet fewer
      girls aspire to science careers than boys. This paradox emerges in middle school,
      when peers begin to play a stronger role in shaping adolescent identities. We use
      complete network data from a single middle school and theories of gender,
      identity, and social distance to explore how friendship patterns might influence
      this gender and science paradox. Three patterns highlight the social dimensions
      of gendered science persistence: (1) boys and girls do not differ in self
      perceived science potential and science career aspirations; (2) consistent with
      gender-based norms, both middle school boys and girls report that the majority of
      their female friends are not science kinds of people; and (3) youth with gender
      inconsistent science aspirations are more likely to be friends with each other
      than youth with gender normative science aspirations. Together, this evidence
      suggests that friendship dynamics contribute to gendered patterns in science
      career aspirations.

PMID- 28491466
TI  - Changes in Retinal Function and Cellular Remodeling Following Experimental
      Retinal Detachment in a Rabbit Model.
AB  - Purpose. To explore functional electroretinographic (ERG) changes and associated
      cellular remodeling following experimental retinal detachment in a rabbit model.
      Methods. Retinal detachment was created in ten rabbits by injecting 0.1 ml
      balanced salt solution under the retina. Fundus imaging was performed 0, 3, 7,
      14, and 21 days postoperatively. ERGs were recorded pre- and 7 and 21 days
      postoperatively. Eyes were harvested on day 21 and evaluated
      immunohistochemically (IHC) for remodeling of second- and third-order neurons.
      Results. Retinal reattachment occurred within two weeks following surgery. No
      attenuation was observed in the photopic or scotopic a- and b-waves. A secondary
      wavefront on the descending slope of the scotopic b-wave was the only ERG result
      that was attenuated in detached retinas. IHC demonstrated anatomical changes in
      both ON and OFF bipolar cells. Bassoon staining was observed in the remodeled
      dendrites. Amacrine and horizontal cells did not alter, but Muller cells were
      clearly reactive with marked extension. Conclusion. Retinal detachment and
      reattachment were associated with functional and anatomical changes. Exploring
      the significance of the secondary scotopic wavefront and its association with the
      remodeling of 2nd- and 3rd-order neurons will shade more light on functional
      changes and recovery of the retina.

PMID- 28491467
TI  - Association between Asymptomatic Unilateral Internal Carotid Artery Stenosis and
      Electrophysiological Function of the Retina and Optic Nerve.
AB  - Purpose. This study was designed to assess retinal and optic nerve bioelectrical
      function in patients with unilateral asymptomatic but hemodynamically significant
      internal carotid artery stenosis (ICAS). Methods. Forty-two subjects with a
      diagnosis of unilateral ICAS and 34 controls were analyzed. Full-field
      electroretinogram (ERG), pattern electroretinogram (PERG), and pattern visual
      evoked potentials, as well as optical coherence tomography and ophthalmological
      examination, were performed. Data analysis included eyes ipsilateral to ICAS
      (EIS) and eyes contralateral to ICAS (ECS). Results. Intraocular pressure was
      significantly decreased in EIS and ECS compared to that in the controls. In the
      macula, both the cube average thickness and cube volume values were significantly
      reduced both in EIS and ECS compared to those in the controls. Similarly, PERG
      P50 and N95 wave amplitudes were significantly smaller in EIS and ECS compared to
      those in the controls. The ERG rod b-wave and rod-cone a-wave amplitudes were
      decreased, and implicit times were significantly prolonged, whereas the OP wave
      index was reduced in EIS compared to that in the controls. No differences in IOP,
      OCT, or ERG and PERG parameters were identified between EIS and ECS. Conclusions.
      Our study demonstrated that retinal bioelectrical function is negatively affected
      by ICAS despite the absence of objective clinical signs and symptoms of ocular
      ischemia.

PMID- 28491469
TI  - Novel Diagnostic and Therapeutic Methods in Ocular Surface and Corneal Diseases.

PMID- 28491468
TI  - Recurrence of Retinopathy of Prematurity in Zone II Stage 3+ after Ranibizumab
      Treatment: A Retrospective Study.
AB  - Objective. To determine the prevalence and risk factors for the recurrence of
      retinopathy of prematurity (ROP) in Zone II Stage 3+ after ranibizumab treatment.
      Methods. This was a retrospective, nonrandomized, noncontrolled study that
      excluded Zone I and aggressive posterior ROP (APROP) cases. Infants who developed
      Zone II Stage 3 ROP with plus disease and underwent initial intravitreal
      injection of ranibizumab (IVR) were recruited. Patients were divided into 2
      groups based on the outcome after initial ranibizumab treatment: recurrence of
      ROP or favorable outcome. Data was collected and analyzed by SPSS 16.0. Results.
      Forty-two patients were included, and 80 eyes with Zone II Stage 3+ were
      subjected to IVR treatment. Eleven of 42 patients (26.2%, 18 eyes) had a
      recurrence of ROP after the initial treatment. On univariate analysis, preretinal
      hemorrhage before treatment was significantly different between the two groups (P
      = 0.000). Multivariate analysis found that preretinal hemorrhage before treatment
      was the only factor associated with the recurrence of ROP in our study (P =
      0.004). Conclusions. The recurrence rate of ROP in Zone II Stage 3+ after initial
      ranibizumab treatment was notable and preretinal hemorrhage before treatment was
      associated with the recurrence of ROP in our study.

PMID- 28491470
TI  - Effect of Active and Passive Smoking on Retinal Nerve Fibre Layer and Ganglion
      Cell Complex.
AB  - Aim. To evaluate the possible structural and functional changes in the retinal
      nerve fibre layer (RNFL) and the ganglion cell complex (GCC) of chronic smokers
      and compare them with those of passive healthy smokers using spectral domain
      optical coherence tomography (SD-OCT) and pattern electroretinogram (PERG).
      Materials and Methods. We include 80 active chronic smokers and 80 age- and sex
      matched healthy passive smokers. After a full ophthalmological examination, SD
      OCT and PERG were tested for all participants. Urinary levels of cotinine and
      creatinine with subsequent calculation of the cotinine creatinine ratio (CCR).
      Results. Inferior and superior quadrants of RNFL were thinner in group I, but
      nasal and temporal quadrants did not show significant difference between the
      groups. There were no significant differences of GCC values between the two
      groups. There was no significant difference of PERG-P50 amplitude and latency;
      however, PERG-N95 showed significant difference between the two groups. Multiple
      regression analyses demonstrated that the number of cigarettes/day, urinary
      cotinine, and PERG-N95 amplitude are the most important determinants for both
      superior and inferior RNFL thicknesses. Conclusion. RNFL thickness decreases in
      chronic, healthy, heavy cigarette smokers, and this thinning is related to the
      number of cigarettes/day, urinary cotinine, and PERG-N95 latency and amplitude.

PMID- 28491471
TI  - A Novel Three-Dimensional Vector Analysis of Axial Globe Position in Thyroid Eye
      Disease.
AB  - Purpose. To define a three-dimensional (3D) vector method to describe the axial
      globe position in thyroid eye disease (TED). Methods. CT data from 59 patients
      with TED were collected and 3D images were reconstructed. A reference coordinate
      system was established, and the coordinates of the corneal apex and the eyeball
      center were calculated to obtain the globe vector [Formula: see text]. The
      measurement reliability was evaluated. The parameters of [Formula: see text] were
      analyzed and compared with the results of two-dimensional (2D) CT measurement,
      Hertel exophthalmometry, and strabismus tests. Results. The reliability of
      [Formula: see text] measurement was excellent. The difference between [Formula:
      see text] and 2D CT measurement was significant (p = 0.003), and [Formula: see
      text] was more consistent with Hertel exophthalmometry than with 2D CT
      measurement (p < 0.001). There was no significant difference between [Formula:
      see text] and Hirschberg test, and a strong correlation was found between
      [Formula: see text] and synoptophore test. When one eye had a larger deviation
      angle than its fellow, its corneal apex shifted in the corresponding direction,
      but the shift of the eyeball center was not significant. The parameters of
      [Formula: see text] were almost perfectly consistent with the geometrical
      equation. Conclusions. The establishment of a 3D globe vector is feasible and
      reliable, and it could provide more information in the axial globe position.

PMID- 28491473
TI  - Clinical Analysis of Ocular Parameters Contributing to Intraoperative Pain during
      Standard Phacoemulsification.
AB  - Purpose. To study the correlation between ocular parameters and subjective pain
      that patients perceived during phacoemulsification. Methods. Medical records of
      142 patients who underwent standard phacoemulsification under topical anesthesia
      between March and August 2016 were retrospectively reviewed. The pain during
      phacoemulsification and 1 h after surgery was assessed and compared using a
      visual analog scale. In addition, demographic data, preoperative biometric
      parameters, and intraoperative surgical parameters were recorded. Results. Mean
      age of patients was 67.49 +/- 12.50 years. The mean pain score was 2.26 +/- 0.85
      during phacoemulsification and 0.40 +/- 0.69 postoperatively. Intraoperative pain
      was significantly associated with higher preoperative intraocular pressure (beta
      = 0.220, P = 0.016), greater anterior chamber depth (beta = 0.210, P = 0.028),
      and greater axial length (beta = 0.181, P = 0.043). Conclusions. To reduce the
      subjective pain when patients have high preoperative intraocular pressure, large
      anterior chamber depth, or great axial length, supplementary procedures may be
      required.

PMID- 28491472
TI  - The Effect of Corneal Refractive Surgery on Glaucoma.
AB  - Laser-assisted refractive procedures have become very popular in the last two
      decades. As a result, a "generation" of patients with altered corneal properties
      is emerging. These patients will require both cataract extraction and glaucoma
      follow-up in the future. Since the glaucoma examination largely depends on the
      corneal properties, the reshaped postrefractive surgery cornea poses a challenge
      in the diagnosis, follow-up, and management of the glaucomatous patient. In order
      to overcome this problem, every patient who is planned to undergo corneal
      refractive surgery must have a thorough glaucoma examination in order for the
      ophthalmologist to be able to monitor their patients for possible glaucoma
      development and/or progression. Some examinations such as tonometry are largely
      affected by the corneal properties, while others such as the evaluation of the
      structures of the posterior pole remain unaffected. However, the new imaging
      modalities of the anterior segment in combination with the most recent advances
      in tonometry can accurately assess the risk for glaucoma and the need for
      treatment.

PMID- 28491474
TI  - The Role of Race and Gender in Nutrition Habits and Self-Efficacy: Results from
      the Young Adult Weight Loss Study.
AB  - Overweight and obesity are a massive public health problem and young adults are
      at high risk for gaining weight once they enter a college. This study sought to
      examine gender and race as they relate to nutrition habits and self-efficacy in a
      population of diverse young adults from the Young Adult Weight Loss Study.
      Participants (N = 62) were 29% males, 38.7% white, 33.8% Asian, and 12.9% African
      American. Males had lower self-efficacy for healthy eating (mean score = 92.5, SD
      = 17.1) compared to females (mean = 102.3, SD = 13.7, p = 0.02). Males had higher
      consumption of sodium compared to females (4308 versus 3239 milligrams/day, p =
      0.01). There were no significant differences across racial subgroups in self
      efficacy for healthy eating (p = 0.67) or self-efficacy for exercise (p = 0.61).
      Higher self-efficacy scores for healthy eating were significantly associated with
      less total sodium (r = -0.37, p = 0.007), greater fruit consumption, and less
      saturated fat. Our results indicate that weight loss interventions should be
      individualized and that there may be specific areas to target that are different
      for men and women. Additional larger studies should be conducted to confirm if
      racial differences exist across nutrition habits and self-efficacy and to confirm
      gender differences noted in this study.

PMID- 28491475
TI  - Referral Patterns and Diagnostic Yield of Lung Scintigraphy in the Diagnosis of
      Acute Pulmonary Embolism.
AB  - Introduction. The purpose of this study is to assess referral patterns and the
      yield of ventilation-perfusion (V/Q) scintigraphy in patients referred for acute
      pulmonary embolism (PE). Methods. We retrospectively reviewed the charts of all
      patients who underwent V/Q studies between April 1, 2008, and March 31, 2010.
      Patients were subdivided into 4 groups based on their referral source: emergency
      department (ED), hospital inpatient ward, outpatient thrombosis clinic, and all
      other outpatient sources. Results. A total of 1008 patients underwent V/Q
      scintigraphy to exclude acute PE. The number of ED, inpatient, thrombosis clinic,
      and outpatient studies was 43 (4.3%), 288 (28.6%), 351 (34.8%), and 326 (32.3%).
      Proportion of patients with contrast contraindication varied significantly among
      the different groups. Of the 1,008 studies, 331 (32.8%) were interpreted as
      normal, 408 (40.5%) as low, 158 (15.7%) as intermediate, and 111 (11.0%) as high
      probability for PE. 68 (6.7%) patients underwent CTPA within 2 weeks following
      V/Q. Conclusion. The rate of nondiagnostic studies is lower than that reported in
      previously published data, with a relatively low rate of intermediate probability
      studies. Only a small fraction of patients undergoing a V/Q scan will require a
      CTPA.

PMID- 28491476
TI  - Increased Intracranial Pressure in the Setting of Enterovirus and Other Viral
      Meningitides.
AB  - Increased intracranial pressure due to viral meningitis has not been widely
      discussed in the literature, although associations with Varicella and rarely
      Enterovirus have been described. Patients with increased intracranial pressure
      and cerebrospinal fluid analysis suggestive of a viral process are sometimes
      classified as having atypical idiopathic intracranial hypertension (IIH).
      However, a diagnosis of IIH requires normal cerebrospinal fluid, and therefore in
      these cases an infection with secondary intracranial hypertension may be a more
      likely diagnosis. Here seven patients are presented with elevated intracranial
      pressure and cerebrospinal fluid suggestive of viral or aseptic meningitis. Of
      these, 1 had Enterovirus and the remainder were diagnosed with nonspecific viral
      meningitis. These data suggest that viral meningitis may be associated with
      elevated intracranial pressure more often than is commonly recognized.
      Enterovirus has previously been associated with increased intracranial pressure
      only in rare case reports.

PMID- 28491477
TI  - The Effect of Diabetic Peripheral Neuropathy on Ground Reaction Forces during
      Straight Walking in Stroke Survivors.
AB  - Purpose. The aim of this present study was to investigate the ground reaction
      forces (GRFs) alterations in stroke survivors with diabetic peripheral neuropathy
      (DPN). Methods. Ten stroke survivors with DPN, 10 stroke survivors without DPN,
      and 10 healthy controls with matched body weight between groups participated in
      this case-control cross-sectional study. Three-dimensional GRFs (anterior
      posterior, medial-lateral, and vertical) were collected at a comfortable walking
      speed using the Nexus Vicon motion analysis system and force plate. The Kruskal
      Wallis test was used to analyze GRFs parameters. Results. We found significant
      alterations of medial-lateral forces of the nonparetic side and vertical forces
      of the paretic side in stroke survivors with DPN compared to stroke survivors
      without DPN and healthy controls. In addition, there were smaller braking and
      lower propulsion peak in anterior-posterior forces, smaller magnitude of medial
      lateral forces, and lower first and second peak of vertical forces in stroke
      survivors with DPN compared to stroke survivors without DPN and healthy controls.
      Conclusion. The study findings identified that GRFs were affected in stroke
      survivors with DPN on both the paretic and the nonparetic sides. Further
      investigations are warranted to explore the impact of DPN on the kinematics and
      muscle activity related to the gait performance in stroke survivors with DPN.

PMID- 28491478
TI  - Rehabilitation Treatment and Progress of Traumatic Brain Injury Dysfunction.
AB  - Traumatic brain injury (TBI) is a major cause of chronic disability. Worldwide,
      it is the leading cause of disability in the under 40s. Behavioral problems,
      mood, cognition, particularly memory, attention, and executive function are
      commonly impaired by TBI. Spending to assist, TBI survivors with disabilities are
      estimated to be costly per year. Such impaired functional outcomes following TBI
      can be improved via various rehabilitative approaches. The objective of the
      present paper is to review the current rehabilitation treatment of traumatic
      brain injury in adults.

PMID- 28491479
TI  - Therapeutic Potentials of Synapses after Traumatic Brain Injury: A Comprehensive
      Review.
AB  - Massive studies have focused on the understanding of the pathobiology of cellular
      and molecular changes and injury mechanisms after traumatic brain injury (TBI),
      but very few studies have specially discussed the role of synapses in the context
      of TBI. This paper specifically highlights the role and therapeutic potentials of
      synapses after TBI. First, we review and conclude how synapses interact with
      constant structural, metabolic, neuroendocrine, and inflammatory mechanisms after
      TBI. Second, we briefly describe several key synaptic proteins involved in
      neuroplasticity, which may be novel neuronal targets for specific intervention.
      Third, we address therapeutic interventions in association with synapses after
      TBI. Finally, we concisely discuss the study gaps in the synapses after TBI, in
      hopes that this would provide more insights for future studies. Synapses play an
      important role in TBI; while the understandings on the synaptic participation in
      the treatments and prognosis of TBI are lacking, more studies in this area are
      warranted.

PMID- 28491481
TI  - Retinal Artery Occlusion Secondary to Buerger's Disease (Thromboangiitis
      Obliterans).
AB  - Purpose. To report a case report of one patient suffering from retinal artery
      occlusion secondary to Buerger's disease, in order to raise awareness to this
      etiology in the differential diagnosis of retinal artery occlusion. Methods. A
      retrospective case report of a patient with retinal artery occlusion secondary to
      Buerger's disease. Data retrieved from the medical records included exposure,
      complaints, visual acuity, clinical findings and imaging, laboratory assessment,
      treatment, disease course, and visual outcome. Results. Diagnosis of retinal
      artery occlusion secondary to Buerger's disease was established based on ruling
      out other causes of retinal artery occlusion. Inflammatory retinal vascular
      disease, permanent vision loss, and macular atrophy were shown in this case.
      Conclusion. The very first case of central retinal artery occlusion (CRAO) in a
      64-year-old male patient with Buerger's disease. Although diagnosing CRAO based
      on both fundoscopic and fluorescein angiographic findings is not difficult,
      revealing underlying condition of CRAO occasionally could be challenging.

PMID- 28491480
TI  - New Treatment Strategies of Depression: Based on Mechanisms Related to
      Neuroplasticity.
AB  - Major depressive disorder is a severe and complex mental disorder. Impaired
      neurotransmission and disrupted signalling pathways may influence
      neuroplasticity, which is involved in the brain dysfunction in depression.
      Traditional neurobiological theories of depression, such as monoamine hypothesis,
      cannot fully explain the whole picture of depressive disorders. In this review,
      we discussed new treatment directions of depression, including modulation of
      glutamatergic system and noninvasive brain stimulation. Dysfunction of
      glutamatergic neurotransmission plays an important role in the pathophysiology of
      depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has
      rapid and lasting antidepressive effects in previous studies. In addition to
      ketamine, other glutamatergic modulators, such as sarcosine, also show potential
      antidepressant effect in animal models or clinical trials. Noninvasive brain
      stimulation is another new treatment strategy beyond pharmacotherapy. Growing
      evidence has demonstrated that superficial brain stimulations, such as
      transcranial magnetic stimulation, transcranial direct current stimulation,
      cranial electrotherapy stimulation, and magnetic seizure therapy, can improve
      depressive symptoms. The antidepressive effect of these brain stimulations may be
      through modulating neuroplasticity. In conclusion, drugs that modulate
      neurotransmission via NMDA receptor and noninvasive brain stimulation may provide
      new directions of treatment for depression. Furthermore, exploring the underlying
      mechanisms will help in developing novel therapies for depression in the future.

PMID- 28491482
TI  - Long-Term Prophylaxis and Pharmacokinetic Evaluation of Intramuscular Nano- and
      Microparticle Decoquinate in Mice Infected with P. berghei Sporozoites.
AB  - Decoquinate nanoparticle and microparticle suspended in an oily vehicle to retard
      drug release are evaluated for long-term malaria prophylaxis. Pharmacokinetic
      studies in normal animals and antimalarial efficacy in liver stage malaria mice
      were conducted at various single intramuscular-decoquinate doses for 2, 4, 6, or
      8 weeks prior to infection with P. berghei sporozoites. The liver stage efficacy
      evaluation was monitored by using an in vivo imaging system. Full causal
      prophylaxis was shown in mice with a single intramuscular dose at 120 mg/kg of
      nanoparticle decoquinate (0.43 MUm) for 2-3 weeks and with microparticle
      decoquinate (8.31 MUm) injected 8 weeks earlier than inoculation. The time above
      MIC of 1,375 hr observed with the microparticle formulation provided a 2.2-fold
      longer drug exposure than with the nanoparticle formulation (624 hr). The
      prophylactic effect of the microparticle formulation observed in mice was shown
      to be 3-4 times longer than the nanoparticle decoquinate formulation.

PMID- 28491484
TI  - Valvular Hemolysis Masquerading as Prosthetic Valve Stenosis.
AB  - The evaluation of prosthetic valves can provide a unique challenge, and a
      thoughtful approach is required. High output states like anemia should be kept in
      the differential when evaluating elevated gradients across prosthetic valves. We
      present the case of a 69-year-old man with a Starr-Edwards prosthetic aortic
      valve who presented with symptoms of congestive heart failure and high
      transvalvular pressure gradients. These symptoms indicate a potential prosthetic
      valve stenosis. His laboratory evaluation results were consistent with valve
      related hemolysis. Resolving his anemia led to a resolution of the symptoms and
      lowered the pressure gradient on follow-up.

PMID- 28491483
TI  - Twelve weeks of dance exergaming in overweight and obese adolescent girls:
      Transfer effects on physical activity, screen time, and self-efficacy.
AB  - BACKGROUND: Given the low levels of physical activity (PA) among adolescent girls
      in the US, there is a need to identify tools to motivate increased PA. Although
      there is limited evidence that adolescents transfer PA from one context to
      another context, exergames (i.e., video games that require gross motor activity)
      may act as a gateway to promote overall PA outside of game play. The purpose of
      this study was to examine potential transfer effects (i.e., influences on
      external behaviors and psychological constructs) of a 12-week exergaming
      intervention on adolescent girls' PA, screen-time, and self-efficacy towards PA,
      as well as the intrinsic motivation of exergaming. METHODS: Participants were 37
      girls aged 14-18 years (65% African American, 35% White) who were overweight or
      obese (body mass index >= 85th percentile) and were recruited from the community
      via school, physicians, news media, and social media sites. Adolescents were
      randomly assigned to a 12-week group exergaming intervention (thirty-six 60 min
      sessions of group-based dance exergaming in a research laboratory using Kinect
      for Xbox 360) or to a no-treatment control group. Outcome variables included
      objectively measured PA (total) and self-reported leisure-time PA (discretionary
      time only) 1-week before vs. 1-week after the intervention; selected type and
      intensity of PA when placed in a gym setting for 30 min ("cardio free choice");
      screen-time; self-efficacy towards PA; and intrinsic motivation towards
      exergaming. RESULTS: Attendance to the exergaming sessions was high (80%).
      Compared to the control group, the intervention group self-reported an increase
      in PA (p = 0.035) and fewer hours watching TV/videos (p = 0.01) after the
      intervention, but there were no significant differences in sedentary, light,
      moderate, or vigorous PA measured by accelerometry. The intervention group
      significantly improved self-efficacy towards PA (p = 0.028). The intervention
      group highly rated intrinsic motivation towards exergaming. CONCLUSION: Twelve
      weeks of exergaming was associated with positive impacts on adolescent girls'
      self-reported PA, television viewing, self-efficacy, and intrinsic motivation.
      Future research is warranted to leverage exergames as an enjoyable, motivating,
      and effective PA tool.

PMID- 28491485
TI  - Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized
      Public Health Issue.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, anti
      inflammatory, and antipyretic activity. Their effect is achieved by the reduction
      in synthesis of prostanoids. Inhibition of prostanoids is responsible for a
      substantial risk of adverse effects. The risk of side effects affecting the
      gastrointestinal tract and kidneys has long been known. The possibilities of
      blood pressure elevation and the development of congestive heart failure are also
      widely recognized. Increased incidence of acute myocardial infarction in clinical
      trials with rofecoxib drew attention to the potential cardiotoxicity of selective
      cyclooxygenase-2 inhibitors, and similarly, concerns have been raised regarding
      the cardiovascular safety of non-selective NSAIDs. The safety of NSAIDs with
      regards to cardiovascular events has been studied in recent years in a large
      number of retrospective and prospective clinical studies and meta-analyses. The
      results indicate that cardiotoxicity is a class effect, but the magnitude of the
      risk is widely variable between individual NSAID drugs. This article aims to
      summarize the available data on the risk of adverse cardiovascular events with
      NSAIDs, the clinical impact of these events and possible underlying mechanisms.

PMID- 28491486
TI  - CREST Calcinosis Affecting the Lumbar and Cervical Spine and the Use of Minimally
      Invasive Surgery.
AB  - Calcinosis in CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility,
      sclerodactyly, and telangiectasia) syndrome can affect the spinal and paraspinal
      areas. We present the first case to our knowledge where a CREST syndrome patient
      required surgery for spinal calcinosis in both the cervical and lumbar areas. A
      66-year-old female with a history of CREST syndrome presented with right-sided
      lower extremity radicular pain. A computed tomography (CT) scan showed bilateral
      lumbar masses (5.8 cm on the right, 3.8 cm on the left) that projected into the
      foramina and into the spinal canal. The patient underwent minimally invasive
      bilateral surgical resection of the paraspinal masses, posterior decompressive
      laminectomy, posterior interbody, and posterolateral fusion. The specimen was
      consistent with the calcinosis of CREST syndrome. The patient's lumbar symptoms
      were relieved, however, two years later she presented with right radicular arm
      pain. A CT scan revealed a large lobulated benign tumor-like lesion on the left
      at C6-C7 encroaching upon the neural foramen and a large right lobulated lesion
      encroaching into the neural foramen with severe compression of the neural foramen
      at the C7-T1 level and extension into the canal, with anterior and posterior
      subluxation present throughout the cervical spine. Surgery was performed, which
      involved cervical mass resections, posterior spinal cord decompression,
      reconstruction, and fusion. The patient did well and has been symptom-free since
      her surgery. Calcinosis of the spine is a known entity that can cause morbidity
      in patients with CREST syndrome. Minimal invasive surgical approaches are
      effective and can be considered for some of these patients.

PMID- 28491488
TI  - Dog attachment and perceived social support in overweight/obese and healthy
      weight children.
AB  - The development of effective and sustainable interventions to treat childhood
      obesity remains both a priority and a challenge. Previous studies support that
      dogs provide social support in overweight adults in obesity interventions, but
      the child-dog relationship is not as well understood. The goal of the study was
      to examine the child-dog relationship among children to inform novel childhood
      obesity interventions including dogs. A cross-sectional study was conducted in
      the Living Laboratory(r) at the Museum of Science, Boston in 2015. Children aged
      8-13, with a dog in the household, answered surveys on pet attachment (Pet
      Relationship Scale), perceived social support from parents and close friends
      (Child and Adolescent Social Support Scale), and had a height and weight
      measurement taken for calculation of body mass index percentile. Overweight and
      obese children (>= 85th body mass index percentile) had greater mean attachment
      score to their dog and less mean perceived social support from their parents and
      friends combined compared to healthy weight children (73.1 +/- 5.6 vs. 68.5 +/-
      7.2, p = 0.037; 110.5 +/- 13.5 vs. 122.9 +/- 14.8, p = 0.015, respectively; n =
      43). In conclusions, children who are overweight/obese report greater mean dog
      attachment and lower mean perceived social support, supporting the concept that
      pet dogs are considered part of overweight/obese children's social support
      networks. Future studies are warranted to evaluate the impact of including pet
      dogs as additional health support in child obesity interventions.

PMID- 28491490
TI  - Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal
      candidiasis.
AB  - We report a rapid acquisition of echinocandin resistance after 12 days of
      micafungin treatment, without prior exposure, in a patient with peritoneal
      candidiasis due to C. glabrata. Isolates recovered before and after treatment
      were compared by multilocus sequence typing. Results of antifungal susceptibility
      testing and FKS mutations were reported. The interest of repeating antifungal
      susceptibility testing for echinocandin molecules during the treatment is
      discussed and a strategy to research FKS mutations proposed.

PMID- 28491489
TI  - The social context moderates the relationship between neighborhood safety and
      adolescents' activities.
AB  - Studies of neighborhood safety and physical activity have typically neglected to
      consider the youth's peer context as a modifier of these relationships. This
      study fills this gap in testing the independent and interactive effects of
      perceived neighborhood safety and time spent with friends and peers on young
      adolescents' physical activity and sedentary behavior. Participants (N = 80; ages
      13-17) completed the Pedestrian/Traffic Safety and Crime Safety subscales of the
      adolescent version of the Neighborhood Environment Walkability Scale (NEWS). An
      experience sampling methodology was used to assess sedentary behaviors/screen
      time and the social context in which physical activity and sedentary
      time/behavior occurred. Physical activity was assessed via accelerometry.
      Multilevel models were used to estimate the relationships between predictors
      (neighborhood safety and social context) and outcomes (physical activity and
      sedentary time/behavior). Frequency of peer/friend interactions moderated the
      relationships between neighborhood safety and adolescents' physical activity and
      sedentary behavior. Specifically, physical activity was more strongly influenced
      by neighborhood safety among adolescents who reported spending less time with
      peers and friends than among those who reported frequent peer interactions. Among
      youths who perceived that their neighborhoods were safer, spending more time with
      friends and peers was related to greater engagement in sedentary activities,
      whereas this was not the case among adolescents who perceived that their
      neighborhoods were less safe. The peer social context moderates the relationship
      between perceived neighborhood safety and adolescents' physical activity and
      sedentary behavior. Improving social interactions at the individual level within
      neighborhoods may decrease concerns of safety.

PMID- 28491491
TI  - Tuberculous pleural effusion occurring concurrently with asbestos-related pleural
      disease.
AB  - An eighty-four-year-old man presented with progressive exertional dyspnea,
      productive cough and weight loss for two months. His physical exam was notable
      for diminished breath sounds at the right base, with dullness to percussion.
      Chest-x-ray showed moderate right-sided pleural effusion and bilateral calcified
      pleural plaques as well as diaphragmatic plaques consistent with asbestos-related
      pleural disease (ARPD). Pleural fluid was exudative with predominantly
      mononuclear cells, negative acid fast bacilli stain, negative cultures, and
      negative cytology for malignant cells. Due to recurrence of the effusion, 4 weeks
      after drainage, thoracoscopic pleural biopsy was planned but pleural fluid
      cultures came back positive for mycobacteria tuberculosis. Patient was started on
      anti-tubercular therapy but treatment had to be stopped due to liver toxicity.
      Patient subsequently developed pneumonia and deteriorated despite antibiotic
      therapy and expired.

PMID- 28491487
TI  - Biomolecular engineering for nanobio/bionanotechnology.
AB  - Biomolecular engineering can be used to purposefully manipulate biomolecules,
      such as peptides, proteins, nucleic acids and lipids, within the framework of the
      relations among their structures, functions and properties, as well as their
      applicability to such areas as developing novel biomaterials, biosensing,
      bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be
      used to design and tune the sizes, shapes, properties and functionality of
      nanomaterials. As such, there are considerable overlaps between nanotechnology
      and biomolecular engineering, in that both are concerned with the structure and
      behavior of materials on the nanometer scale or smaller. Therefore, in
      combination with nanotechnology, biomolecular engineering is expected to open up
      new fields of nanobio/bionanotechnology and to contribute to the development of
      novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights
      recent studies using engineered biological molecules (e.g., oligonucleotides,
      peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and
      ligands) combined with functional nanomaterials in nanobio/bionanotechnology
      applications, including therapeutics, diagnostics, biosensing, bioanalysis and
      biocatalysts. Furthermore, this review focuses on five areas of recent advances
      in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering,
      (c) protein engineering, (d) chemical and enzymatic conjugation technologies, and
      (e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and
      nanobiosystems are anticipated to emerge as next-generation platforms for
      bioelectronics, biosensors, biocatalysts, molecular imaging modalities,
      biological actuators, and biomedical applications.

PMID- 28491492
TI  - Associations between hippocampal morphometry and neuropathologic markers of
      Alzheimer's disease using 7 T MRI.
AB  - Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established
      pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9
      Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were
      scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial
      distances using automated segmentation techniques. Hippocampal slices were
      stained for amyloid beta (Abeta), tau, and cresyl violet to evaluate neuronal
      counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were
      manually traced so that the neuronal counts, Abeta, and tau burden could be
      obtained for each region. We used linear regression to detect associations
      between hippocampal atrophy in 3D, clinical diagnosis and total as well as
      subfield pathology burden measures. As expected, we found significant
      correlations between hippocampal radial distance and mean neuronal count, as well
      as diagnosis. There were subfield specific associations between hippocampal
      radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and
      subiculum. These results provide further validation for the European Alzheimer's
      Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized
      Hippocampal Segmentation Protocol (HarP).

PMID- 28491493
TI  - Brainstem shape is affected by clinical course in the neonatal intensive care
      unit.
AB  - The brainstem, critical for motor function, autonomic regulation, and many
      neurocognitive functions, undergoes rapid development from the third trimester.
      Accordingly, we hypothesized it would be vulnerable to insult during this period,
      and that a difficult clinical course in the neonatal intensive care unit (NICU)
      would affect development, and be reflected through atypical shape. Our study
      population consisted of 66 neonates - all inpatients from the NICU at Victoria
      Hospital, London Health Sciences Centre, ON, Canada, of which 45 entered the
      final analysis. The cohort varied in gestational age (GA) and ranged from
      neurologically healthy to severely brain-injured. Structural MRI was used to
      quantify brainstem shape at term-equivalent age. From these images, brainstems
      were semi-automatically segmented and co-registered across subjects. The anterior
      posterior dimensions on a sagittal maximum intensity projection were used as the
      basis for shape comparison. Factor analysis was used to summarize variation in
      shape and in clinical course to determine three shape factors and three clinical
      factors, and their relationship assessed using correlation. A factor driven by
      low GA and associated complications correlated with alterations in the posterior
      medulla, while a factor driven by complications independent of GA correlated with
      alterations in the midbrain. Additionally, single clinical measures most
      representative of their respective clinical factor (days in NICU; days on
      ventilation) predicted the changes. Thus, different clinical courses in the NICU
      may have different effects on the shape of the brainstem, and may mediate some of
      the distinct neurodevelopmental profiles observed in premature and brain-injured
      neonates.

PMID- 28491494
TI  - The relationship between morphological lesion, magnetic source imaging, and
      intracranial stereo-electroencephalography in focal cortical dysplasia.
AB  - Magnetoencephalography (MEG) is a useful non-invasive technique for presurgical
      evaluation of focal cortical dysplasia patients. We aimed at clarifying the
      precise spatial relationship between the spiking volume determined with MEG, the
      seizure onset zone and the lesional volume in patients with focal cortical
      dysplasia. We studied the spatial relationships between the MEG spiking volume
      determined with a recent analysis pipeline, the seizure-onset zone location
      determined with a quantitative index calculated from intracranial EEG signals
      ('Epileptogenicity Index') and the lesional volume delineated on brain MRI in 11
      patients with Focal Cortical Dysplasia explored with Stereo
      electroencephalography (SEEG). A significant correlation between the MEG spiking
      activity and the Epileptogenicity Index was found in 8/11 patients. 7/8 patients
      were operated upon and had good surgical outcome. For three patients, no
      correlation between Epileptogenicity Index and spiking activity was observed;
      only one of those three patients had good surgical outcome. The lesion was at
      least partially overlapping with the seizure-onset zone in 8/9 patients with a
      lesion clearly identifiable by MRI. However, 57% of the SEEG epileptogenic
      contacts were located outside of the lesional volume. Lastly 44% of the highly
      epileptogenic SEEG contacts were located within the spiking volume and 22% of
      them were located exclusively in the spiking volume and not in the lesion. For
      7/9 patients with a lesion, < 50% of epileptogenic SEEG contacts were included
      within the lesion: for 5/7 patients MEG provided an added value for targeting the
      epileptogenic region through intracranial electrodes, while for two of seven
      patients MEG detected only a few extralesional epileptogenic contacts. Our study
      suggests that modeling of the spiking volume with MEG is a promising tool to
      localize non-invasively the seizure-onset zone in patients with focal cortical
      dysplasia. Combined with brain MRI, MEG modeling of the spiking volume
      contributes to delineate the spatial extent of the seizure-onset zone.

PMID- 28491497
TI  - Complete genome sequence of a natural compounds producer, Streptomyces violaceus
      S21.
AB  - The complete genome sequence of Streptomyces violaceus strain S21, a valuable
      natural compounds producer isolated from the forest soil, is firstly presented
      here. The genome comprised 7.91M bp, with a G + C content of 72.65%. A range of
      genes involved in pathways of secondary product biosynthesis were predicted. The
      genome sequence is available at DDBJ/EMBL/Genbank under the accession number
      CP020570. This genome is annotated with 6856 predicted genes identifying the
      natural product biosynthetic gene clusters in S. violaceus.

PMID- 28491498
TI  - Two mechanisms of termination of idiopathic reentrant ventricular tachycardia
      originating from the left coronary cusp/right coronary cusp commissure with
      nonglobal capture.

PMID- 28491495
TI  - Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation
      in alcohol dependence.
AB  - Substance-dependent individuals often lack the ability to adjust decisions
      flexibly in response to the changes in reward contingencies. Prediction errors
      (PEs) are thought to mediate flexible decision-making by updating the reward
      values associated with available actions. In this study, we explored whether the
      neurobiological correlates of PEs are altered in alcohol dependence. Behavioral,
      and functional magnetic resonance imaging (fMRI) data were simultaneously
      acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy
      controls (HC) during a probabilistic reward-guided decision-making task with
      dynamically changing reinforcement contingencies. A hierarchical Bayesian
      inference method was used to fit and compare learning models with different
      assumptions about the amount of task-related information subjects may have
      inferred during the experiment. Here, we observed that the best-fitting model was
      a modified Rescorla-Wagner type model, the "double-update" model, which assumes
      that subjects infer the knowledge that reward contingencies are anti-correlated,
      and integrate both actual and hypothetical outcomes into their decisions.
      Moreover, comparison of the best-fitting model's parameters showed that ADP were
      less sensitive to punishments compared to HC. Hence, decisions of ADP after
      punishments were loosely coupled with the expected reward values assigned to
      them. A correlation analysis between the model-generated PEs and the fMRI data
      revealed a reduced association between these PEs and the BOLD activity in the
      dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was
      observed in the DLPFC when positive and negative PE signals were analyzed
      separately. The right DLPFC activity in ADP showed a reduced correlation with
      positive PEs. On the other hand, ADP, particularly the patients with high
      dependence severity, recruited the left DLPFC to a lesser extent than HC for
      processing negative PE signals. These results suggest that the DLPFC, which has
      been linked to adaptive control of action selection, may play an important role
      in cognitive inflexibility observed in alcohol dependence when reinforcement
      contingencies change. Particularly, the left DLPFC may contribute to this
      impaired behavioral adaptation, possibly by impeding the extinction of the
      actions that no longer lead to a reward.

PMID- 28491496
TI  - Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI.
AB  - Focal cortical dysplasias (FCDs) are a range of malformations of cortical
      development each with specific histopathological features. Conventional
      radiological assessment of standard structural MRI is useful for the localization
      of lesions but is unable to accurately predict the histopathological features.
      Quantitative MRI offers the possibility to probe tissue biophysical properties in
      vivo and may bridge the gap between radiological assessment and ex-vivo
      histology. This review will cover histological, genetic and radiological features
      of FCD following the ILAE classification and will explain how quantitative voxel-
      and surface-based techniques can characterise these features. We will provide an
      overview of the quantitative MRI measures available, their link with biophysical
      properties and finally the potential application of quantitative MRI to the
      problem of FCD subtyping. Future research linking quantitative MRI to FCD
      histological properties should improve clinical protocols, allow better
      characterisation of lesions in vivo and tailored surgical planning to the
      individual.

PMID- 28491499
TI  - Sinus bradycardia and chronotropic incompetence associated with single-agent
      itraconazole antifungal therapy: A case report.

PMID- 28491500
TI  - First direct human evidence of a probable implantable cardioverter-defibrillator
      lead-related scar serving as a substrate for ventricular tachycardia.

PMID- 28491501
TI  - Right coronary artery ostial stenosis associated with idiopathic ventricular
      tachycardia ablation.

PMID- 28491502
TI  - Focal atrial fibrillation presenting in the origin of atrial tachycardia.

PMID- 28491503
TI  - Progressive modification of rotors in persistent atrial fibrillation by stepwise
      linear ablation.

PMID- 28491504
TI  - Successful detection of a high-energy electrical short circuit and a "rescue"
      shock using a novel automatic shocking-vector adjustment algorithm.

PMID- 28491505
TI  - Fracture and retrieval of an Achieve circular mapping catheter in and from a
      pulmonary vein during cryoballoon ablation for atrial fibrillation.

PMID- 28491506
TI  - An unusual approach to intractable AVNRT in a pediatric patient.

PMID- 28491507
TI  - Thrombotic cardiac tamponade after transseptal puncture.

PMID- 28491508
TI  - Perimitral atrial flutter associated with a protected coronary sinus after a Maze
      IV procedure and concomitant mitral annulus repair.

PMID- 28491509
TI  - Shock-induced right ventricular pacing failure caused by a short circuit:
      Uncommon but life-threatening complication of the Riata lead.

PMID- 28491510
TI  - Abrupt increase in impedance measurements as detected via remote monitoring: What
      is the cause?

PMID- 28491511
TI  - Pseudo typical atrial flutter occurring after cavotricuspid isthmus ablation in a
      patient with a prior history of Senning operation.

PMID- 28491512
TI  - Functional permanent 2:1 atrioventricular block treated with cardioneuroablation:
      Case report.

PMID- 28491513
TI  - Erroneous shock by an AED: Importance of obtaining AED tracing to prevent
      inappropriate ICD implantation.

PMID- 28491514
TI  - Ablation of parahisian ventricular focus.

PMID- 28491515
TI  - Arrhythmogenic triggers associated with an autonomic response from a
      posteroseptal region after extensive ablation in a patient with long-standing
      atrial fibrillation.

PMID- 28491516
TI  - Preferential properties with decremental conduction of the Marshall vein between
      the coronary sinus and left superior pulmonary vein.

PMID- 28491517
TI  - First case of epicardial ablation to coexistent J waves in the inferior leads in
      a patient with clinical diagnosis of Brugada syndrome.

PMID- 28491518
TI  - Simultaneous isolation of the four pulmonary veins by single-sided antral
      ablation.

PMID- 28491519
TI  - A rare variant of pulmonary vein drainage.

PMID- 28491520
TI  - A case of incessant VT from an intramural septal focus: Ethanol or bipolar
      ablation?

PMID- 28491521
TI  - Transjugular lead fragment extraction to improve tricuspid regurgitation.

PMID- 28491522
TI  - Accelerated idioventricular rhythm after left atrial tachycardia ablation as a
      marker of acute coronary ischemia.

PMID- 28491523
TI  - Left anterior descending artery spasm after radiofrequency catheter ablation for
      ventricular premature contractions originating from the left ventricular outflow
      tract.

PMID- 28491524
TI  - Successful catheter ablation of idiopathic ventricular tachycardia originating
      from the top of the left ventricular posterior papillary muscle near the chordae
      tendineae: Usefulness of intracardiac three-dimensional echocardiography.

PMID- 28491525
TI  - Multiple monomorphic ventricular tachycardias in a structurally normal heart: A
      case report.

PMID- 28491526
TI  - Social anxiety provoked by speech-induced atrial tachycardia.

PMID- 28491527
TI  - Laser-assisted extraction of a pacing lead with a supraclavicular course.

PMID- 28491528
TI  - Usefulness of a 2-F catheter electrode in a case with successful electrical
      isolation of remarkably hypoplastic right inferior pulmonary vein.

PMID- 28491529
TI  - Ventricular tachycardia secondary to abandoned epicardial pacemaker lead.

PMID- 28491530
TI  - Overcoming an impossible anatomy with a novel left ventricular active fixation
      lead in the coronary sinus: A case report.

PMID- 28491531
TI  - A case of successful termination of an atrial tachycardia ablated from the
      pulmonary artery during rapid ventricular pacing.

PMID- 28491533
TI  - Exome sequencing identifies a novel mutation in the MYH6 gene in a family with
      early-onset sinus node dysfunction, ventricular arrhythmias, and cardiac arrest.

PMID- 28491532
TI  - Successful treatment of flecainide overdose with sustained mechanical circulatory
      support.

PMID- 28491534
TI  - Role of the His bundle in verapamil-sensitive idiopathic left ventricular
      tachycardia.

PMID- 28491535
TI  - Parasternal intercostal approach as an alternative to subxiphoid approach for
      epicardial catheter ablation: A case report.

PMID- 28491536
TI  - Air entrapment causing early inappropriate shocks in a patient with a
      subcutaneous cardioverter-defibrillator.

PMID- 28491537
TI  - Serious case of the hiccups.

PMID- 28491538
TI  - Options for ventricular tachycardia ablation after double valve replacement.

PMID- 28491539
TI  - Breast tissue expanders and implantable cardioverter-defibrillator: An unusual
      interaction.

PMID- 28491540
TI  - Rhabdomyolysis complicating percutaneous radiofrequency ablation of persistent
      atrial fibrillation.

PMID- 28491541
TI  - Commotio cordis due to high-velocity projectile ejected from an industrial
      lawnmower.

PMID- 28491542
TI  - Implantation of the subcutaneous implantable cardioverter-defibrillator with
      retroperitoneal generator placement in a child with hypoplastic left heart
      syndrome.

PMID- 28491543
TI  - A true case of wandering pacemaker.

PMID- 28491544
TI  - Isolated right ventricular failure and abnormal hemodynamics caused by right
      ventricular pacing are reversed with cardiac resynchronization therapy.

PMID- 28491545
TI  - Right-sided subcutaneous implantable cardioverter-defibrillator placement in a
      patient with dextrocardia, tetralogy of Fallot, and conduction disease.

PMID- 28491546
TI  - Persistent sinus node suppression caused by thrombotic occlusion of an
      arteriovenous fistula: A report of two cases.

PMID- 28491547
TI  - Short QT and atrial fibrillation: A KCNQ1 mutation-specific disease. Late follow
      up in three unrelated children.

PMID- 28491548
TI  - Pacemaker-induced tachycardia in a DDI-programmed ICD: What is the mechanism?

PMID- 28491549
TI  - Extensive atrial fibrosis in a patient with systemic lupus erythematosus and
      atrial fibrillation.

PMID- 28491550
TI  - Successful catheter ablation of hemodynamically significant ventricular
      tachycardia in a patient with biventricular assist device support.

PMID- 28491551
TI  - Early repolarization syndrome: A case report focusing on dynamic
      electrocardiographic changes before ventricular arrhythmias and genetic analysis.

PMID- 28491552
TI  - Radiofrequency ablation-assisted extraction of a pacing lead fragment.

PMID- 28491553
TI  - Absence of a resetting phenomenon suggests that a sling works as a part of the
      supraventricular tachycardia circuit involving twin atrioventricular nodes: A
      case of corrected transposition of the great arteries.

PMID- 28491554
TI  - Induction of tachycardia confined within a pulmonary vein by electrical
      cardioversion of atrial fibrillation: Is it proof of reentry?

PMID- 28491555
TI  - Duelling pacemakers: Unexpected pacemaker interaction resulting from a
      proprietary rate smoothing algorithm.

PMID- 28491556
TI  - Pseudo-conduction block at the mitral isthmus in a patient with epicardial
      impulse propagation through the vein of Marshall.

PMID- 28491558
TI  - Successful implantation of a subcutaneous cardiac defibrillator in a patient with
      a preexisting deep brain stimulator.

PMID- 28491557
TI  - Robot-assisted delayed extraction of retained Lasso catheter combined with mitral
      valve repair and arrhythmia ablation.

PMID- 28491559
TI  - Successful ablation of refractory neonatal atrial flutter.

PMID- 28491560
TI  - Recurrent commotio cordis: Deja vu.

PMID- 28491561
TI  - Periesophageal vagal nerve injury following catheter ablation of atrial
      fibrillation: A case report and review of the literature.

PMID- 28491562
TI  - Inappropriate shocks by subcutaneous implantable cardioverter-defibrillator due
      to T-wave oversensing in hyperkalemia leading to ventricular fibrillation.

PMID- 28491563
TI  - The use of noninvasive ECG imaging for examination of a patient with Brugada
      syndrome.

PMID- 28491564
TI  - Direct visualization of induced steam pops during radiofrequency ablation.

PMID- 28491565
TI  - Mahaim-type accessory pathway and right bundle branch electroanatomic
      delineation.

PMID- 28491566
TI  - Challenges in the diagnosis and management of idiopathic ventricular
      fibrillation.

PMID- 28491567
TI  - Adjusting voltage criteria can unmask conducting channels in a patient with
      arrhythmogenic right ventricular cardiomyopathy and ventricular tachycardia.

PMID- 28491568
TI  - First-in-human case of repeat pulmonary vein isolation by targeting visual
      interlesion gaps using the direct endoscopic ablation catheter after single ring
      pulmonary vein isolation.

PMID- 28491570
TI  - MediGuide-assisted atrial flutter ablation in a patient with a HeartMate II left
      ventricular assist device.

PMID- 28491569
TI  - Ventricular fibrillation in lone atrial fibrillation as clinical manifestation of
      latent Brugada syndrome: Usefulness of flecainide testing.

PMID- 28491572
TI  - Nonobstructive septal hypertrophy in a young adult provoking recurrent
      polymorphic ventricular tachycardia successfully treated with transaortic and
      transventricular septal myectomy: A case report.

PMID- 28491571
TI  - Isolated atrioventricular block of unknown origin in the adult and autoimmunity:
      diagnostic and therapeutic considerations exemplified by 3 anti-Ro/SSA-associated
      cases.

PMID- 28491573
TI  - Recurrent suspected myocarditis combined with infrahisian conduction disturbances
      revealing a desminopathy.

PMID- 28491574
TI  - Pathology after combined epicardial and endocardial ablation for ventricular
      tachycardia in a postmortem heart with hypertrophic cardiomyopathy.

PMID- 28491575
TI  - A case series and review of the literature regarding coronary artery
      complications associated with coronary sinus catheter ablation.

PMID- 28491576
TI  - QRS normalization during atrial pacing in a patient with complete left bundle
      branch block: What is your diagnosis?

PMID- 28491577
TI  - CT-fusion-guided transseptal puncture in a patient with atrial fibrillation and
      absent right superior vena cava.

PMID- 28491578
TI  - Fasciculoventricular accessory pathways following repair of ventricular septal
      defects.

PMID- 28491579
TI  - Ankyrin-2 variants associated with idiopathic ventricular fibrillation storm in
      patients with intermittent early repolarization pattern.

PMID- 28491580
TI  - Relation of overweight and symptomatic atrial fibrillation: A case report.

PMID- 28491581
TI  - Discrete prepotentials with an isoelectric segment at the successful ablation
      site in the right ventricular outflow tract and pulmonary artery junction in a
      case with a ventricular arrhythmia.

PMID- 28491582
TI  - Atrial pacing for the management of ventricular arrhythmias in Andersen-Tawil
      syndrome.

PMID- 28491583
TI  - Implantation of a cardiac resynchronization therapy and defibrillation system
      using a robotic approach.

PMID- 28491584
TI  - Atrial fibrillation ablation performed in the developing world: A description of
      the first atrial fibrillation ablation performed in Cambodia.

PMID- 28491585
TI  - Ventricular fibrillation a rare complication during head-up tilt test.

PMID- 28491586
TI  - A very rare abnormal course of the thoracic venous system: Long journey to the
      right ventricle.

PMID- 28491587
TI  - Unusual mechanism of complete atrioventricular block following atrial flutter
      ablation.

PMID- 28491588
TI  - The lack of effect of sotalol in short QT syndrome patients carrying the T618I
      mutation in the KCNH2 gene.

PMID- 28491589
TI  - Circular mapping recordings in a persistent left superior vena cava during atrial
      tachycardia: Was isolation achieved?

PMID- 28491590
TI  - Left ventricle penetration-A rare complication of transseptal puncture and
      catheter ablation for supraventricular tachycardia.

PMID- 28491591
TI  - Rapidly formed right ventricular thrombus detected by intracardiac
      echocardiography before catheter ablation in a case of arrhythmogenic right
      ventricular cardiomyopathy.

PMID- 28491592
TI  - Intentional anodal capture of a left ventricular quadripolar lead enhances
      resynchronization equally with multipoint pacing.

PMID- 28491593
TI  - Congenital long QT syndrome: A difficult journey for one young survivor.

PMID- 28491594
TI  - Successful stent implantation for superior vena cava injury during transvenous
      lead extraction.

PMID- 28491596
TI  - An unusual atrioventricular accessory pathway with an oblique course.

PMID- 28491595
TI  - High-power bipolar ablation for incessant ventricular tachycardia utilizing a
      deep midmyocardial septal circuit.

PMID- 28491597
TI  - The presence of left atrial posterior wall fibrillation despite restoration of
      sinus rhythm after posterior box ablation.

PMID- 28491598
TI  - Nothing inside the heart - Combining epicardial pacing with the S-ICD.

PMID- 28491599
TI  - Visualization of pulmonary vein-left atrium lesions using delayed-enhancement
      magnetic resonance imaging after cryothermal balloon catheter ablation: A case
      report.

PMID- 28491600
TI  - Incessant bundle branch reentrant ventricular tachycardia in a patient with
      corrected transposition of the great arteries.

PMID- 28491601
TI  - A case of ventricular fibrillation triggered by ventricular premature
      depolarizations exiting from different sites of the Purkinje network.

PMID- 28491602
TI  - A balloon occlusion technique to overcome the convective warming effect of
      coronary sinus blood flow on cryoablation.

PMID- 28491603
TI  - Patients with hemophilia: Unique challenges for atrial fibrillation management.

PMID- 28491604
TI  - A case series of anomalous high pacing lead impedances in normally functioning
      leads.

PMID- 28491605
TI  - Parsing a perplexing paroxysmal pathway.

PMID- 28491606
TI  - Left atrial access via an unroofed coronary sinus to eliminate fast/slow atypical
      AVNRT: A case report.

PMID- 28491607
TI  - Reuse of a 20-year-old lead: An abandoned lead reactivated.

PMID- 28491608
TI  - Prolonged high-power endocardial ablation of epicardial microreentrant VT from
      the LV summit in a patient with nonischemic cardiomyopathy.

PMID- 28491609
TI  - Combination of a leadless pacemaker and subcutaneous defibrillator: First in
      human report.

PMID- 28491610
TI  - Long-term follow-up of minimally invasive video-assisted thoracoscopic surgery
      with epicardial radiofrequency ablation for complex cases of inappropriate sinus
      tachycardia.

PMID- 28491611
TI  - Acquired right atrial appendage to right ventricle accessory pathway in a lateral
      tunnel Fontan patient: Successful ablation via transconduit approach.

PMID- 28491612
TI  - Radiofrequency ablation of common atrial flutter via right subclavian/jugular
      vein access in a patient with bilateral lower limb venous obstruction: Importance
      of contact force monitoring during mapping and ablation.

PMID- 28491613
TI  - Late atrial tachycardia originating from donor pulmonary vein in a double lung
      transplant recipient.

PMID- 28491614
TI  - Choking-induced cardiac arrest unmasks a diagnosis of catecholaminergic
      polymorphic ventricular tachycardia.

PMID- 28491615
TI  - To eat, or not to eat...?: A live video case of swallowing-induced atrial
      tachycardia.

PMID- 28491616
TI  - Partial extravenous course of cardiac pacemaker leads. A major risk during device
      assisted extraction.

PMID- 28491617
TI  - Direct visualization of an iatrogenic septal defect in a reanimated human heart.

PMID- 28491618
TI  - State of the journal 2016: HeartRhythm Case Reports.

PMID- 28491619
TI  - Feasibility of tricuspid valve-in-valve replacement in a patient with
      transvalvular pacemaker.

PMID- 28491621
TI  - Central venous catheter fracture during pacemaker lead extraction.

PMID- 28491620
TI  - Turning a blind eye to the far field: Are we burying the evidence? A case of
      abrupt catastrophic implantable cardioverter defibrillator lead failure causing
      sudden death.

PMID- 28491622
TI  - Combined use of TandemHeart percutaneous ventricular assist device and
      Stereotaxis magnetic navigation during cardiac ablation procedure.

PMID- 28491623
TI  - Simultaneous lead extraction and vacuum-assisted vegetation removal.

PMID- 28491624
TI  - Salvage of diagnostic quality of image acquired by low-radiation-dose
      prospectively ECG-triggered coronary CTA during ventricular trigeminy: A case
      report of a novel image processing method.

PMID- 28491625
TI  - Premature extrastimulus pace-mapping to identify the origin of ventricular
      premature depolarizations.

PMID- 28491626
TI  - Bradycardia-dependent rise in the atrial capture threshold early after cardiac
      pacemaker implantation in patients with sick sinus syndrome.

PMID- 28491627
TI  - A novel GJA1 mutation causing familial oculodentodigital dysplasia with dilated
      cardiomyopathy and arrhythmia.

PMID- 28491628
TI  - Physiological rate adaptation in a child with chronotropic incompetence through
      closed-loop stimulation using epicardial leads.

PMID- 28491629
TI  - The runaway defibrillator...A case of an implantable cardioverter-defibrillator
      that failed communication and deactivation with a magnet.

PMID- 28491630
TI  - Retrieval of a transcatheter pacemaker in sheep after a mid-term implantation
      time.

PMID- 28491631
TI  - Epicardial mapping and ablation of the right ventricle substrate during
      flecainide testing in Brugada syndrome.

PMID- 28491632
TI  - Rapidly progressive cardiac sarcoidosis: Initial presentation with sinus node
      dysfunction and right bundle branch block.

PMID- 28491633
TI  - Extraction of a Micra Transcatheter Pacing System: First-in-human experience.

PMID- 28491634
TI  - Irregular wide QRS complex tachycardia in a patient with pulmonary hypertension:
      What is the mechanism?

PMID- 28491635
TI  - Single-catheter validation of bidirectional block during atrial flutter ablation.

PMID- 28491636
TI  - Multiple atrial thrombi in a neonate presenting with supraventricular
      tachycardia.

PMID- 28491637
TI  - Dobutamine-induced midcavitary gradients do not cause dyspnea.

PMID- 28491638
TI  - Standard cardiac resynchronization therapy with a second right ventricular lead
      for severe right ventricular heart failure in 2 patients with repaired tetralogy
      of Fallot.

PMID- 28491639
TI  - Fibrin glue patch for pacemaker lead perforation of the right ventricular free
      wall: A case report.

PMID- 28491640
TI  - Swallow-induced syncope: A case report of atrial tachycardia originating from the
      SVC.

PMID- 28491641
TI  - Benefit of magnetic resonance-conditional cardiac resynchronization therapy
      defibrillator: A case of cardiac sarcoidosis-involved cervical extradural lesion.

PMID- 28491642
TI  - A novel ACTC1 mutation in a young boy with left ventricular noncompaction and
      arrhythmias.

PMID- 28491643
TI  - Ventricular tachycardia in iron man.

PMID- 28491644
TI  - Upper septal transformation of verapamil-sensitive idiopathic left ventricular
      tachycardia during catheter ablation: Wolf in sheep's clothing?

PMID- 28491645
TI  - Tachycardia-induced cardiomyopathy long after a pacemaker implantation for the
      treatment of unusual 2:1 atrioventricular block: What is the mechanism?

PMID- 28491646
TI  - Pericardial adhesions as a consequence of cryoballoon ablation detected during
      the hybrid AF ablation procedure.

PMID- 28491647
TI  - Catheter ablation for the treatment of persistent atrial fibrillation:
      Maintenance of sinus rhythm with left atrial appendage and coronary sinus
      isolation after multiple ablation procedures.

PMID- 28491648
TI  - Successful atrioventricular junction ablation in a patient with situs inversus
      with dextrocardia and complex venous anatomy.

PMID- 28491649
TI  - Atrial Tachycardia in a Patient With Fabry's Disease.

PMID- 28491650
TI  - Familial long QT syndrome and late development of dilated cardiomyopathy in a
      child with a KCNQ1 mutation: A case report.

PMID- 28491651
TI  - Left ventricular tachycardia ablation in a toddler via a transapical approach: A
      new tool for the armamentarium.

PMID- 28491652
TI  - Implantation of ileofemoral stents: A novel approach for bilateral occlusions of
      the iliofemoral vein in a patient with a Glenn operation.

PMID- 28491653
TI  - Incessant atrioventricular nodal reentrant tachycardia with tachycardia-induced
      cardiomyopathy, biventricular thrombosis, and pulmonary emboli.

PMID- 28491654
TI  - Phrenic nerve pacing in a patient with congenital atresia of the right superior
      vena cava and persistent left superior vena cava: An alternative approach when
      utilizing cryoballoon ablation.

PMID- 28491655
TI  - Paradoxical preexcitation following successful ablation of a concealed accessory
      pathway.

PMID- 28491656
TI  - Successful interventional management of catastrophic coronary arterial air
      embolism during atrial fibrillation ablation.

PMID- 28491657
TI  - ICD lead abandonment is without risk? A case of "lead on lead crime".

PMID- 28491658
TI  - An atrial flutter in a 40-year-old woman with situs inversus, transposition of
      the great arteries, atrial switch, and interruption of the inferior vena cava.

PMID- 28491659
TI  - Reduced combined ventricular output and increased oxygen extraction fraction in a
      fetus with complete heart block demonstrated by MRI.

PMID- 28491660
TI  - Occlusion of a congenital right coronary-to-vena cava superior fistula induces
      temporary junctional bradycardia and atrial fibrillation.

PMID- 28491661
TI  - Diagnosis of lead-induced tricuspid regurgitation.

PMID- 28491662
TI  - Intermittent failure to capture: What is the mechanism?

PMID- 28491663
TI  - Epicardial ablation of ventricular tachycardia in a patient with Becker muscular
      dystrophy.

PMID- 28491664
TI  - Successful retrieval of a broken circular mapping catheter after entrapment in
      the tricuspid valve apparatus.

PMID- 28491665
TI  - Mechanical esophageal deviation: an approach for pulmonary vein reconnection
      attributed to esophageal heating.

PMID- 28491666
TI  - An atypical journey during a "typical" EP case.

PMID- 28491667
TI  - Supraspinatus pocket: An alternative pacemaker location for patients with no
      prepectoral access.

PMID- 28491668
TI  - PentaRay entrapment in a mechanical mitral valve during catheter ablation of
      atrial fibrillation.

PMID- 28491669
TI  - Isolation of an arrhythmogenic roof vein with the guide of a circular mapping
      catheter in a case with paroxysmal atrial fibrillation.

PMID- 28491670
TI  - Premature ventricular contractions with two QRS morphologies originate from one
      focus in great cardiac vein.

PMID- 28491671
TI  - Extraction of a CardioFix neurostimulator with concomitant laser-assisted lead
      and intracardiac cardiac defibrillator extraction due to Staphylococcus aureus
      pocket infection.

PMID- 28491672
TI  - Correlation between functional and ultrastructural substrate in Brugada syndrome.

PMID- 28491673
TI  - Failure of ICD therapy in lethal arrhythmogenic right ventricular cardiomyopathy
      type 5 caused by the TMEM43 p.Ser358Leu mutation.

PMID- 28491674
TI  - Normalization of QT interval duration in a long QT syndrome patient during
      pregnancy and the postpartum period due to sex hormone effects on cardiac
      repolarization.

PMID- 28491675
TI  - Management of life-threatening flecainide overdose: A case report and review of
      the literature.

PMID- 28491676
TI  - High-dose loperamide abuse-associated ventricular arrhythmias.

PMID- 28491677
TI  - Flecainide and elevated liver enzymes in alpha1-antitrypsin deficiency.

PMID- 28491678
TI  - Transhepatic radiofrequency ablation of a cavotricuspid isthmus-dependent atrial
      flutter.

PMID- 28491679
TI  - Cardiac resynchronization therapy device implantation guided by electroanatomic
      mapping system when contrast medium infusion is contraindicated.

PMID- 28491680
TI  - A Medwatch review of reported events in patients who discontinued rivaroxaban
      (XARELTO) therapy in response to legal advertising.

PMID- 28491681
TI  - Novel CALM3 mutations in pediatric long QT syndrome patients support a CALM3
      specific calmodulinopathy.

PMID- 28491682
TI  - Radiofrequency ablation of premature ventricular contractions originating from
      the aortomitral continuity localized by use of a novel noninvasive epicardial and
      endocardial electrophysiology system.

PMID- 28491683
TI  - Cryoablation of an atrioventricular nodal reentrant tachycardia in a patient with
      an implanted deep brain stimulator.

PMID- 28491684
TI  - Repeated molecular genetic analysis in Brugada syndrome revealed a novel disease
      associated large deletion in the SCN5A gene.

PMID- 28491686
TI  - Absence of exit block due to direct capture of the left atrial appendage: A
      visual confirmation.

PMID- 28491685
TI  - Radiofrequency wire-facilitated transseptal access using a superior approach for
      atrial fibrillation ablation in a patient with inferior vena cava obstruction.

PMID- 28491687
TI  - Subcutaneous ICD implant complicated by an intraperitoneal lead course and device
      infection.

PMID- 28491688
TI  - Pacemaker-induced takotsubo cardiomyopathy.

PMID- 28491689
TI  - Concomitant pulsus and pseudoelectrical alternans in severe systolic dysfunction.

PMID- 28491690
TI  - Dexamethasone suppresses long QT phenotype in patient with acute promyelocytic
      leukemia treated with arsenic.

PMID- 28491691
TI  - A case of Durata ICD lead coil externalization: Inside-out lead abrasion?

PMID- 28491692
TI  - Intermittent failure of pacing output caused by algorithm to prevent T-wave
      oversensing.

PMID- 28491693
TI  - Congenital heart disease confounding the diagnosis of arrhythmogenic right
      ventricular cardiomyopathy.

PMID- 28491694
TI  - Emergent use of an MRI-conditional external pacemaker in a patient with sinus
      arrest facilitating diagnosis of a temporal lobe neoplasm.

PMID- 28491695
TI  - Successful totally thoracoscopic management of a superior vena cava perforation
      with a pacemaker lead.

PMID- 28491696
TI  - A rare case of epicardial left ventricular sutureless screw-in lead placement
      causing left anterior descending artery stenosis.

PMID- 28491697
TI  - Swallowing-induced atrial tachycardia arising from superior vena cava:
      Significant involvement of parasympathetic nerve activity.

PMID- 28491698
TI  - Idiopathic left innominate vein stenosis during pacemaker implantation with
      venoplasty in a retrograde approach.

PMID- 28491699
TI  - Orthostatic increase in defibrillation threshold leading to defibrillation
      failure and prolonged cardiac arrest in a sitting position: Lessons from a
      patient's near-fatal experience.

PMID- 28491700
TI  - Percutaneous extraction of a 20-year-old Accufix pacemaker lead complicated by
      intraoperative protrusion of its J retention wire.

PMID- 28491701
TI  - Undetected ventricular fibrillation in a single-chamber implantable cardioverter
      defibrillator: When the far-field channel sees more than the intraventricular
      channel.

PMID- 28491702
TI  - Late resolution of pacemaker lead-related severe tricuspid regurgitation and
      right ventricular dysfunction after percutaneous lead extraction: A case report
      and review of the literature.

PMID- 28491704
TI  - Pre-excited tachycardia: Atrial tachycardia with a bystander left lateral
      accessory pathway.

PMID- 28491703
TI  - Cardiac arrest in an adolescent with Uhl's anomaly: Two unusual cardiac
      arrhythmia mechanisms.

PMID- 28491705
TI  - Implantation of a leadless cardiac pacemaker for recurrent pocket infections.

PMID- 28491706
TI  - Radiofrequency catheter ablation for treatment of premature ventricular
      contractions triggering ventricular fibrillation from the right ventricular
      outflow tract in a patient with early repolarization syndrome.

PMID- 28491707
TI  - Low room temperature can trigger ventricular fibrillation in J wave syndromes.

PMID- 28491708
TI  - Successful catheter ablation using real-time ultrasound-assisted 3-D
      electroanatomical mapping system for atrioventricular accessory pathway in a 1
      year-old girl with criss-cross heart.

PMID- 28491709
TI  - Atrial tachycardia in an electrically dissociated native right atrium after heart
      transplantation.

PMID- 28491710
TI  - Treating an infected transcatheter pacemaker system via percutaneous extraction.

PMID- 28491711
TI  - Preferential conduction during focal atrial tachycardia arising from the
      noncoronary cusp.

PMID- 28491712
TI  - "Left ventricular" AV nodal reentrant tachycardia: Case report and review of the
      literature.

PMID- 28491713
TI  - Cavotricuspid isthmus high-density mapping.

PMID- 28491714
TI  - Delayed cardiac perforation of the Durata implantable cardioverter-defibrillator
      lead more than 1 year after implantation.

PMID- 28491715
TI  - Ablation of a symptomatic spontaneous automatic focus arising from an
      atriofascicular fiber.

PMID- 28491716
TI  - B-cell lymphoma of the pericardium presenting with ventricular tachycardia with a
      successful catheter ablation.

PMID- 28491717
TI  - 'Runaway' vagal nerve stimulator: a case of cyclic asystole.

PMID- 28491719
TI  - Abdominal implantable cardioverter-defibrillator placement in a patient requiring
      bilateral chest radiation therapy.

PMID- 28491718
TI  - T-wave oversensing during drug challenge test after subcutaneous implantable
      cardioverter-defibrillator implantation in a patient with Brugada syndrome.

PMID- 28491720
TI  - Wolff-Parkinson-White as a bystander in a patient with aborted sudden cardiac
      death.

PMID- 28491721
TI  - A unique case of pulmonary embolism presenting as a paroxysmal atrial tachycardia
      instigated only by recumbency and stooping.

PMID- 28491722
TI  - Appearance of J wave in the inferolateral leads and ventricular fibrillation
      provoked by mild hypothermia in a patient with Brugada syndrome.

PMID- 28491723
TI  - Substernal implantation of a subcutaneous implantable cardioverter-defibrillator
      in a patient with preexisting Hemodialysis Reliable Outflow graft.

PMID- 28491724
TI  - Spectrum of cardiac manifestations from aconitine poisoning.

PMID- 28491725
TI  - Recurrent and late-onset coronary spasms after cryoballoon ablation procedure in
      a patient with atrial fibrillation.

PMID- 28491726
TI  - Endocardial-only catheter ablation with substantial improvement in ventricular
      fibrillation recurrences in a patient with Brugada syndrome.

PMID- 28491727
TI  - Cardiac resynchronization therapy in coronary sinus atresia delivered using
      leadless endocardial pacing.

PMID- 28491728
TI  - A case of Takotsubo cardiomyopathy showing two modes of initiation for
      ventricular fibrillation: Augmented J-wave and torsade de pointes with QT
      prolongation.

PMID- 28491729
TI  - Late presentation of constrictive pericarditis after limited epicardial ablation
      for inappropriate sinus tachycardia.

PMID- 28491730
TI  - Graft-versus-host disease: A rare complication of device implantation.

PMID- 28491731
TI  - Repeat inappropriate defibrillator discharges following defibrillator
      implantation. What is the mechanism and treatment?

PMID- 28491732
TI  - High-density mapping of the tachycardia circuit in atrioventricular nodal
      reentrant tachycardia.

PMID- 28491733
TI  - Reply to the Editor - Regarding swallowing-induced atrial tachycardia arising
      from superior vena cava: Significant involvement of parasympathetic nerve
      activity.

PMID- 28491734
TI  - To the Editor-Swallowing-induced atrial tachycardia arising from superior vena
      cava: significant involvement of parasympathetic nerve activity.

PMID- 28491735
TI  - Air emboli during the procedure of transcatheter left atrial appendage closure.

PMID- 28491736
TI  - An unusual cause of HV prolongation.

PMID- 28491737
TI  - Catheter ablation of ventricular tachycardia in the setting of electrical storm
      after revascularization of a chronic total occlusion of the right coronary
      artery: An uncommon presentation of reperfusion arrhythmia.

PMID- 28491738
TI  - IRX3 variant as a modifier of Brugada syndrome with frequent ventricular
      fibrillation.

PMID- 28491739
TI  - Incremental value of electroanatomical mapping for the diagnosis of
      arrhythmogenic right ventricular cardiomyopathy in a patient with sustained
      ventricular tachycardia.

PMID- 28491740
TI  - Inhibition of pacing in a dependent patient with an implantable cardioverter
      defibrillator and a left ventricular assist device.

PMID- 28491742
TI  - A transseptal puncture hazard that was close!

PMID- 28491741
TI  - Inappropriate shocks in a patient with a subcutaneous implantable cardioverter
      defibrillator.

PMID- 28491743
TI  - Quinidine for Brugada syndrome: Panacea or poison?

PMID- 28491744
TI  - Coronary artery vasospasm during catheter cryoablation of left ventricular summit
      nonsustained ventricular tachycardia.

PMID- 28491745
TI  - Transvenous approach to pacemaker lead implantation for sinus node dysfunction
      after extracardiac lateral tunnel Fontan conduit placement.

PMID- 28491746
TI  - Getting to the right left atrium: Catheter ablation of atrial fibrillation and
      mitral annular flutter in cor triatriatum.

PMID- 28491747
TI  - Flecainide-induced incessant orthodromic atrioventricular reentrant tachycardia
      in Wolff-Parkinson-White syndrome: Uneven depression of accessory pathway
      conduction.

PMID- 28491748
TI  - Percutaneous extraction of a pulmonary artery catheter inadvertently sewn to the
      right atrial wall.

PMID- 28491749
TI  - Recurrent flash pulmonary edema due to rate-dependent left bundle branch block.

PMID- 28491750
TI  - Electroanatomical high-density mapping of different tachycardias in the right
      atrium after heart transplantation.

PMID- 28491752
TI  - Vagally mediated ventricular arrhythmia in Brugada syndrome.

PMID- 28491753
TI  - Clinical problem solving: Maneuvering around a narrow complex tachycardia in a
      patient with Mustard repair for transposition of the great arteries.

PMID- 28491751
TI  - Structural interplay of KV7.1 and KCNE1 is essential for normal repolarization
      and is compromised in short QT syndrome 2 (KV7.1-A287T).

PMID- 28491754
TI  - State of the Journal 2017: HeartRhythm Case Reports.

PMID- 28491755
TI  - Pericardial-esophageal fistula complicating cryoballoon ablation for refractory
      atrial fibrillation.

PMID- 28491756
TI  - Radiation-associated plasmacytoma following catheter ablation for atrial
      fibrillation.

PMID- 28491757
TI  - Successful use of bivalirudin in place of heparin infusion for pulmonary vein
      isolation using a cryoballoon catheter in a patient with heparin allergy.

PMID- 28491758
TI  - Atrial fibrillation associated with Wolff-Parkinson-White syndrome in a patient
      with concomitant Brugada syndrome.

PMID- 28491759
TI  - Termination of anticoagulation therapy at 45 days after concomitant atrial
      fibrillation catheter ablation and left atrial appendage occlusion resulting in
      device-related thrombosis and stroke.

PMID- 28491760
TI  - Hierarchical analysis of electrograms to guide termination of persistent atrial
      fibrillation.

PMID- 28491761
TI  - Use of Biotronik closed loop pacemaker to treat recurrent syncope in pediatric
      patient with dysautonomia.

PMID- 28491762
TI  - Cardiac resynchronization therapy in persistent left superior vena cava: Can you
      do it two-leads-only?

PMID- 28491764
TI  - Pulmonary vein stenosis after second-generation cryoballoon ablation for atrial
      fibrillation.

PMID- 28491763
TI  - Who is the guilty among these two silent killers?

PMID- 28491765
TI  - Systemic infection due to subcutaneous implantable cardioverter-defibrillator
      implantation: Importance of early recognition and treatment of device pocket
      related complications.

PMID- 28491766
TI  - Progressive electrical remodeling in apical hypertrophic cardiomyopathy leading
      to implantable cardioverter-defibrillator sensing failure during ventricular
      fibrillation.

PMID- 28491767
TI  - Interference dissociation in the presence of dual atrioventricular nodal
      physiology.

PMID- 28491768
TI  - Successful prenatal management of ventricular tachycardia and second-degree
      atrioventricular block in fetal long QT syndrome.

PMID- 28491769
TI  - Surgical and electrophysiological considerations in the management of a patient
      with a subcutaneous implantable cardioverter-defibrillator undergoing coronary
      artery bypass surgery.

PMID- 28491770
TI  - Successful treatment of tachycardia-induced cardiomyopathy secondary to dual
      atrioventricular nodal nonreentrant tachycardia using cryoablation.

PMID- 28491771
TI  - A novel de novo calmodulin mutation in a 6-year-old boy who experienced an
      aborted cardiac arrest.

PMID- 28491772
TI  - Recurrent syncope due to glossopharyngeal neuralgia.

PMID- 28491773
TI  - Inappropriate subcutaneous implantable cardioverter-defibrillator therapy due to
      R-wave amplitude variation: Another challenge in device management.

PMID- 28491774
TI  - Dissociation of right and left AV conduction: What is the mechanism?

PMID- 28491775
TI  - A case of an ablation catheter entrapped in the pulmonary vein during atrial
      fibrillation ablation requiring open heart surgery for removal.

PMID- 28491776
TI  - Early improvement of pacing threshold following primary right coronary
      angioplasty.

PMID- 28491777
TI  - A simple method to ablate left-sided accessory pathways in a patient with
      coronary sinus ostial atresia and persistent left superior vena cava: A case
      report.

PMID- 28491778
TI  - Substernal ICD lead implantation in a patient not suitable for subcutaneous ICD
      implantation without venous access due to superior vena cava syndrome.

PMID- 28491780
TI  - Complexity of ranolazine and phenytoin use in an infant with long QT syndrome
      type 3.

PMID- 28491779
TI  - Missed diagnosis: Dual right ventricular lead perforation resulting in chest
      pain.

PMID- 28491781
TI  - Radiofrequency catheter ablation for drug-refractory paroxysmal atrial
      fibrillation in a patient with Ebstein's anomaly.

PMID- 28491782
TI  - Ultrarapid identification of activation channels within the scar using high
      density mapping from a basket catheter.

PMID- 28491783
TI  - Atrioventricular block and pause-dependent torsade de pointes.

PMID- 28491784
TI  - Vein of Marshall partially isolated with radiofrequency ablation from the
      endocardium.

PMID- 28491785
TI  - Junctional ectopic tachycardia secondary to myocarditis associated with sudden
      cardiac arrest.

PMID- 28491786
TI  - Trans-Fontan baffle placement of an endocardial systemic ventricular pacing lead.

PMID- 28491787
TI  - Ventricular tachycardia slower than the rate cut-off of a subcutaneous cardiac
      defibrillator sensed and successfully treated as a result of oversensing.

PMID- 28491788
TI  - Unstable accelerated idioventricular rhythm in a neonate with congenital heart
      disease.

PMID- 28491789
TI  - Resuscitated sudden cardiac death due to diminutive coronary artery syndrome.

PMID- 28491790
TI  - Electroanatomic mapping of atrial tachycardia-Manual vs automated annotation.

PMID- 28491791
TI  - Malfunction of an MRI-Conditional Pacemaker Following an MRI.

PMID- 28491792
TI  - Flecainide treats a novel KCNJ2 mutation associated with Andersen-Tawil syndrome.

PMID- 28491793
TI  - Bicuspid aortic valve supporting supravalvular "substrate" for multiple
      ventricular tachycardias.

PMID- 28491794
TI  - Successful catheter ablation of recipient left ventricular tachycardia 26 years
      after heterotopic heart transplantation.

PMID- 28491795
TI  - Electrophysiological evidence of localized reentry as a trigger and driver of
      atrial fibrillation at the junction of the superior vena cava and right atrium.

PMID- 28491796
TI  - LAMP2 shines a light on cardiomyopathy in an athlete.

PMID- 28491798
TI  - Simultaneous atrioventricular node ablation and leadless pacemaker implantation.

PMID- 28491799
TI  - To the Editor - Cardiac resynchronization therapy in coronary sinus atresia
      delivered using leadless endocardial pacing.

PMID- 28491797
TI  - Bundle branch reentrant ventricular tachycardia after transcatheter aortic valve
      replacement.

PMID- 28491800
TI  - Reply to the Editor - Regarding Cardiac Resynchronization Therapy in Coronary
      Sinus Atresia Delivered Using Leadless Endocardial Pacing.

PMID- 28491801
TI  - Iatrogenic pleuropericardial communication: A rare complication of percutaneous
      epicardial mapping.

PMID- 28491802
TI  - Protecting the right phrenic nerve during catheter ablation: Techniques and
      anatomical considerations.

PMID- 28491803
TI  - Near-zero fluoroscopy implantation of dual-chamber pacemaker in pregnancy using
      electroanatomic mapping.

PMID- 28491804
TI  - A surgeon with symptomatic ventricular tachycardia while operating and
      exacerbated by left lateral decubitus position: Too much of a stretch?

PMID- 28491805
TI  - Worsening of mitral valve regurgitation after radiofrequency catheter ablation of
      ventricular arrhythmia originating from a left ventricular papillary muscle.

PMID- 28491806
TI  - Atypical long QT syndrome phenotype in heterozygous/homozygous KCNQ1 Ala590Thr.

PMID- 28491807
TI  - Microreentrant left atrial tachycardia circuit mapped with an ultra-high-density
      mapping system.

PMID- 28491808
TI  - Cardiac contractility modulation therapy: Are there superresponders?

PMID- 28491809
TI  - Early-stage left atrial intramural hemorrhage mimicking partial coronary sinus
      thrombosis in a patient who received ablation for atrial tachyarrhythmias.

PMID- 28491810
TI  - Oversensing of atrial fibrillatory waves in a subcutaneous implantable
      cardioverter-defibrillator.

PMID- 28491811
TI  - An infected cyst due to a congenital pulmonary airway malformation.

PMID- 28491812
TI  - Acremonium pneumonia in an AIDS patient.
AB  - Acremonium is a saprophytic fungus mostly causing superficial skin, nail, or
      ocular infections after traumatic inoculation. However, it is being recently
      recognized as one of the opportunistic infections in immunocompromised patients
      including neutropenia, malignancies, chronic granulomatous disease (CGD) and
      transplant recipients. To our knowledge there have been no reported cases of
      Acremonium infection, related to HIV or AIDS. We present a case of Acremonium
      pneumonia in a patient with no past medical history who was found to have AIDS.

PMID- 28491813
TI  - Toxic shock syndrome due to community-acquired methicillin-resistant
      Staphylococcus aureus infection: Two case reports and a literature review in
      Japan.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus has been spreading
      worldwide, including in Japan. However, few cases of toxic shock syndrome caused
      by Community-acquired methicillin-resistant Staphylococcus aureus have been
      reported in Japan. We report 2 cases, in middle-aged women, of toxic shock
      syndrome due to Community-acquired methicillin-resistant Staphylococcus aureus
      via a vaginal portal of entry. The first patient had used a tampon and the second
      patient had vaginitis due to a cleft narrowing associated with vulvar lichen
      sclerosus. Both patients were admitted to our hospital with septic shock and
      severe acute kidney injury and subsequently recovered with appropriate antibiotic
      treatment. In our review of the literature, 8 cases of toxic shock syndrome
      caused by Community-acquired methicillin-resistant Staphylococcus aureus were
      reported in Japan. In these 8 cases, the main portals of entry were the skin and
      respiratory tract; however, the portal of entry of Community-acquired methicillin
      resistant Staphylococcus aureus from a vaginal lesion has not been reported in
      Japan previously.

PMID- 28491814
TI  - Varicella-zoster virus (VZV) multifocal vasculopathy in a patient with systemic
      lupus erythematosus - a diagnostic and treatment dilemma.
AB  - Cerebral vasculopathy due to varicella-zoster virus (VZV) infection is well
      documented. We report a fatal case of VZV multifocal vasculopathy in a patient
      with systemic lupus erythematosus (SLE) who presented with subacute changes in
      mental status and had multiple areas of hemorrhagic infarcts on brain imaging.
      However, the correct diagnosis was delayed by several confounding factors
      including the absence of zoster rash, normal cerebral angiography, persistently
      low cerebrospinal fluid (CSF) glucose and negative initial polymerase chain
      reaction (PCR) for VZV DNA in the CSF. Our case and literature review suggests
      that the sensitivity of PCR for VZV DNA in the CSF is low in VZV vasculopathy and
      clinical suspicion of this disease in the setting of characteristic imaging
      findings could be crucial to timely diagnosis.

PMID- 28491815
TI  - Lethal pulmonary hemorrhage syndrome due to Leptospira infection transmitted by
      pet rat.
AB  - Human infection with Leptospira interrogans can be life-threatening. Multiple
      organ involvement frequently presents with liver and kidney failure, less
      commonly including severe hemolysis and pulmonary hemorrhage syndrome. Here, we
      present a fulminant case of leptospirosis presenting with hemolysis and pulmonary
      hemorrhage. A formerly healthy 34 year old patient presented to a rural hospital
      with dyspnea and hemoptysis after a week of influenza-like symptoms. Initial
      assessment revealed severe sepsis, acute kidney failure and severe hemolysis.
      Within the next 29 h, a multi-organ failure developed, which could eventually not
      be reversed despite mechanical ventilation, venovenous extracorporeal membrane
      oxygenation, continuous renal replacement therapy, plasmapheresis and
      extracorporeal cytokine absorbent therapy. The diagnosis of leptospirosis was
      made after the patient died. The transmitting animal was a pet rat. Leptospirosis
      has to be considered in case of rapid multi-organ failure presenting with
      pulmonary hemorrhage.

PMID- 28491816
TI  - Treatment adherence during childhood in individuals with phenylketonuria: Early
      signs of treatment discontinuation.
AB  - INTRODUCTION: Phenylketonuria (PKU) is an autosomal recessive disorder
      characterized by a deficiency in phenylalanine (Phe) hydroxylase activity. Early
      diagnosis and continuous treatment with a low Phe diet prevents severe
      neurological and cognitive impairment. AIMS: 1. Analyze how treatment adherence
      evolves through infancy, childhood, and early adolescence in individuals with
      PKU. 2. Identify early signs of treatment discontinuation. METHODOLOGY: This
      longitudinal, retrospective study included 75 children diagnosed through newborn
      screening, ages 7 to 13 years. Data on blood Phe concentration, number of blood
      samples sent, proportion of samples with Phe concentrations over the recommended
      range, and number of visits to the metabolism clinic were recorded. Logistic
      regression analysis was used to identify the variables that predict treatment
      discontinuation before 13 years of age. RESULTS: A progressive increase in mean
      blood Phe concentrations with age was identified. The greatest increase occurred
      between the first and second years of life. By age ten, mean Phe blood
      concentration of the group was above the recommended range. The proportion of
      samples with Phe concentrations over the recommended range also increased with
      age, from an average of 13% during the first year of life to 67% in early
      adolescence. Sixty-eight percent of the children attended the outpatient clinic
      and sent samples from birth to the time of the study. Individuals who
      discontinued follow-up showed significantly higher mean blood Phe concentrations
      (360 vs. 220.9 MUmol/L; p = 0.004) and the proportion of samples over the
      recommended range (37% vs. 12% p = 0.002) was significantly higher during the
      second year of life. Mean age for children who discontinued treatment was 5.5
      years of age. Blood Phe concentration values at 12 to 23 months of age and at 6
      to 8 years of age significantly predicted treatment discontinuation before 13
      years of age. CONCLUSION: Treatment adherence in PKU diminishes with age. Early
      signs of treatment discontinuation can be identified during the second year of
      life, allowing preventive interventions in high risk groups.

PMID- 28491817
TI  - A 45,X/46,XY Male with Orchidopexy Diagnosed with Mixed Germ Cell Tumor After 21
      year Follow-up.
AB  - A case of a 45,X/46,XY boy with gonadal dysgenesis is presented. The patient
      showed hypospadias and right undescended testis. He underwent underwent repair
      surgery for hypospadias, right orchidopexy, and bilateral testicular biopsy.
      Testicular biopsy revealed no malignant finding. He was followed-up annually by
      scrotum palpation. When the patient grew up to 24 years old, he was diagnosed to
      have right testicular tumor. High orchiectomy revealed pT1 seminoma. The
      management of undescended testis in men with gonadal dysgenesis and disordered
      sexual development is discussed.

PMID- 28491818
TI  - Pancake Kidney Found Inside Abdominal Cavity: Rare Case with Literature Review.
AB  - The cake or lump kidney is a rare form of fusion. The pancake kidney is always
      found in the pelvic cavity, in the greater or lesser pelvis. However, we report a
      case of pancake kidney which was found inside abdominal cavity while
      investigating 32-year-old male for lower limb pain. CT scan with IV contrast
      reveals 'fused mass situated in the right side of abdominal cavity with course
      uncrossed ureters opening separately into the urinary bladder found incidentally
      with patient work up'. Pancake kidney in this case was managed conservatively
      without any complication. This malformation is usually present in pelvic cavity,
      so blood supply is almost constant but in rare cases might be different and
      follows location of this anomaly.

PMID- 28491819
TI  - Optimization of prodigiosin production by Serratia marcescens using crude
      glycerol and enhancing production using gamma radiation.
AB  - Prodigiosin is a red pigment produced by Serratia marcescens. Prodigiosin is
      regarded as a promising drug owing to its reported characteristics of possessing
      anti-microbial, anti-cancer, and immunosuppressive activity. A factorial design
      was applied to generate a set of 32 experimental combinations to study the
      optimal conditions for pigment production using crude glycerol obtained from
      local biodiesel facility as carbon source for the growth of Serratia marcescens.
      The maximum production (870 unit/cell) was achieved at 22  degrees C, at pH 9
      with the addition of 1% (w/v) peptone and 109 cell/ml inoculum size after 6 days
      of incubation. Gamma radiation at dose 200 Gy was capable of doubling the
      production of the pigment using the optimized conditions and manipulating
      production temperature. Our results indicate that we have designed an economic
      medium supporting enhanced Serratia marcescens MN5 prodigiosin production giving
      an added value for crude glycerol obtained from biodiesel industry.

PMID- 28491820
TI  - Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate.
AB  - Perturbation of endoplasmic reticulum (ER) homeostasis results in a stress
      condition termed "ER stress" determining the activation of a finely regulated
      program defined as unfolded protein response (UPR) and whose primary aim is to
      restore this organelle's physiological activity. Several physiological and
      pathological stimuli deregulate normal ER activity causing UPR activation, such
      as hypoxia, glucose shortage, genome instability, and cytotoxic compounds
      administration. Some of these stimuli are frequently observed during uncontrolled
      proliferation of transformed cells, resulting in tumor core formation and stage
      progression. Therefore, it is not surprising that ER stress is usually induced
      during solid tumor development and stage progression, becoming an hallmark of
      such malignancies. Several UPR components are in fact deregulated in different
      tumor types, and accumulating data indicate their active involvement in tumor
      development/progression. However, although the UPR program is primarily a pro
      survival process, sustained and/or prolonged stress may result in cell death
      induction. Therefore, understanding the mechanism(s) regulating the cell
      survival/death decision under ER stress condition may be crucial in order to
      specifically target tumor cells and possibly circumvent or overcome tumor
      resistance to therapies. In this review, we discuss the role played by the UPR
      program in tumor initiation, progression and resistance to therapy, highlighting
      the recent advances that have improved our understanding of the molecular
      mechanisms that regulate the survival/death switch.

PMID- 28491821
TI  - Editorial: Exploring Cancer Metabolic Reprogramming through Molecular Imaging.

PMID- 28491822
TI  - Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline
      Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial
      Cultures.
AB  - Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in
      clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of
      SNARE proteins, which prevents cells from releasing neurotransmitters from
      vesicles, while the effects of minocycline are related to the inhibition of p38
      activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their
      direct impact on glial cells is not fully known. Therefore, the aim of the
      present study was to determine the effects of those drugs on microglial and
      astroglial activity after lipopolysaccharide (LPS) stimulation and their
      potential synergistic action. Our results show that BoNT/A and minocycline
      influenced primary microglial cells by inhibiting intracellular signaling
      pathways, such as p38, ERK1/2, NF-kappaB, and the release of pro-inflammatory
      factors, including IL-1beta, IL-18, IL-6, and NOS2. We have revealed that, in
      contrast to minocycline, BoNT/A treatment did not decrease LPS-induced release of
      pro-inflammatory factors in the astroglia. In addition, BoNT/A decreased SNAP-23
      in both types of glial cells and also SNAP-25 expressed only in astrocytes.
      Moreover, BoNT/A increased TLR2 and its adaptor protein MyD88, but not TLR4
      exclusively in microglial cells. Furthermore, we have shown the impact of BoNT/A
      on microglial and astroglial cells, with a particular emphasis on its molecular
      target, TLR2. In contrast, minocycline did not affect any of those factors. We
      have revealed that despite of different molecular targets, minocycline, and
      BoNT/A reduced the release of microglia-derived pro-inflammatory factors. In
      conclusion, we have shown that BoNT/A and minocycline are effective drugs for the
      management of neuroinflammation by dampening the activation of microglial cells,
      with minocycline also affecting astroglial activity.

PMID- 28491823
TI  - Comparative Proteomics Reveals Differences in Host-Pathogen Interaction between
      Infectious and Commensal Relationship with Campylobacter jejuni.
AB  - Campylobacter jejuni is the leading food-borne poisoning in industrialized
      countries. While the bacteria causes disease in humans, it merely colonizes the
      gut in poultry or pigs, where seems to establish a commensal relationship. Until
      now, few studies have been conducted to elucidate the relationship between C.
      jejuni and its different hosts. In this work, a comparative proteomics approach
      was used to identify the underlying mechanisms involved in the divergent outcome
      following C. jejuni infection in human and porcine host. Human (INT-407) and
      porcine (IPEC-1) intestinal cell lines were infected by C. jejuni for 3 h (T3h)
      and 24 h (T24h). C. jejuni infection prompted an intense inflammatory response at
      T3h in human intestinal cells, mainly characterized by expression of proteins
      involved in cell spreading, cell migration and promotion of reactive oxygen
      species (ROS). Proteomic analysis evidenced significantly regulated biofunctions
      in human cells related with engulfment and endocytosis, and supported by
      canonical pathways associated to infection such as caveolar- and clathrin
      mediated endocytosis signaling. In porcine IPEC-1 cells, inflammatory response as
      well as signaling pathways that control cellular functions such as cell
      migration, endocytosis and cell cycle progression resulted downregulated. These
      differences in the host response to infection were supported by the different
      pattern of adhesion and invasion proteins expressed by C. jejuni in human and
      porcine cells. No marked differences in expression of virulence factors involved
      in adaptive response and iron acquisition functions were observed. Therefore, the
      results of this study suggest that both host and pathogen factors are responsible
      for commensal or infectious character of C. jejuni in different hosts.

PMID- 28491824
TI  - Rabies Virus Infection Induces Microtubule Depolymerization to Facilitate Viral
      RNA Synthesis by Upregulating HDAC6.
AB  - Rabies virus (RABV) is the cause of rabies, and is associated with severe
      neurological symptoms, high mortality rate, and a serious threat to human health.
      Although cellular tubulin has recently been identified to be incorporated into
      RABV particles, the effects of RABV infection on the microtubule cytoskeleton
      remain poorly understood. In this study, we show that RABV infection induces
      microtubule depolymerization as observed by confocal microscopy, which is closely
      associated with the formation of the filamentous network of the RABV M protein.
      Depolymerization of microtubules significantly increases viral RNA synthesis,
      while the polymerization of microtubules notably inhibits viral RNA synthesis and
      prevents the viral M protein from inducing the formation of the filamentous
      network. Furthermore, the histone deacetylase 6 (HDAC6) expression level
      progressively increases during RABV infection, and the inhibition of HDAC6
      deacetylase activity significantly decreases viral RNA synthesis. In addition,
      the expression of viral M protein alone was found to significantly upregulate
      HDAC6 expression, leading to a substantial reduction in its substrate, acetylated
      alpha-tubulin, eventually resulting in microtubule depolymerization. These
      results demonstrate that HDAC6 plays a positive role in viral transcription and
      replication by inducing microtubule depolymerization during RABV infection.

PMID- 28491825
TI  - HCMV activation of ERK-MAPK drives a multi-factorial response promoting the
      survival of infected myeloid progenitors.
AB  - Viral binding and entry provides the first trigger of a cell death response and
      thus how human cytomegalovirus (HCMV) evades this - particularly during latent
      infection where a very limited pattern of gene expression is observed - is less
      well understood. It has been demonstrated that the activation of cellular
      signalling pathways upon virus binding promotes the survival of latently infected
      cells by the activation of cell encoded anti-apoptotic responses. In CD34+ cells,
      a major site of HCMV latency, ERK signalling is important for survival and we now
      show that the activation of this pathway impacts on multiple aspects of cell
      death pathways. The data illustrate that HCMV infection triggers activation of
      pro-apoptotic Bak which is then countered through multiple ERK-dependent
      functions. Specifically, ERK promotes ELK1 mediated transcription of the key
      survival molecule MCL-1, along with a concomitant decrease of the pro-apoptotic
      BIM and PUMA proteins. Finally, we show that the elimination of ELK-1 from CD34+
      cells results in elevated Bak activation in response to viral infection,
      resulting in cell death. Taken together, these data begin to shed light on the
      poly-functional response elicited by HCMV via ERK-MAPK to promote cell survival.

PMID- 28491826
TI  - Acellular pertussis vaccine efficacy: An updated systematic review and meta 
      analysis.
AB  - Background: Recent studies indicate an increased incidence of pertussis disease
      in recent years. The aim of this study was to evaluate the efficacy of the
      acellular vaccine for children (as a replacement of current whole cell vaccine in
      the Expanded Program on Immunization) and for high-risk adults in Iran through
      updating current best available evidence. Methods: We performed a systematic
      literature review in relevant databases we focused on previously published
      systematic reviews to select those that address our questions. The AMSTAR
      (assessing the methodological quality of systematic reviews) tool was used for
      screening available reviews. Then search in databases was done until Feb 2014 to
      update the evidence. We pooled results using meta-analysis methods by Stata
      statistical package. Results: Eleven systematic review articles were included in
      the initial evaluation. In the end, two systematic reviews on acellular vaccine
      booster doses and the acellular vaccine in children were selected as the baseline
      evidence. In the update phase, new clinical trials were screened, and the results
      were updated. Overall pooled estimate of relative efficacy of acellular to whole
      cell was 0.68 (95% CI, 0.55-0.81) for children immunization Pooled estimates for
      the efficacy of acellular versus placebo were 0.70 (95% CI, 0.60-0.80). Overall
      pooled estimate of efficacy of booster dose of acellular was 0.87(95% CI, 0.85
      0.88) compared to placebo. In addition pooled estimate of acellular vaccine
      efficacy based on response to antigen was 0.78(95% CI, 0.64-0.93) in highrisk
      group. Conclusion: The results show higher performance and safety of the
      acellular vaccine in the prevention of pertussis in children versus the whole
      cell vaccine. Moreover, the efficacy of the acellular vaccine in high-risk adult
      groups is acceptable. This study provides evidence in favor of the introduction
      of an acellular vaccine to the national program of immunization. Studies on cost
      effectiveness and aspects of policy analysis are recommended.

PMID- 28491827
TI  - Effect of exercise training on saliva brain derived neurotrophic factor, catalase
      and vitamin c.
AB  - Background: The balance between production of Reactive Oxygen Species (ROS) and
      antioxidant defense in the body has important health implications. The aim of
      this study was to investigate the changes in salivary antioxidants: catalase,
      vitamin C and brain-derived neurotrophic factor (BDNF), in sedentary men at rest
      and after acute exhaustive exercise. Methods: This randomized controlled clinical
      trial (The registry code IRCT2011053212431N1) recruited twenty-five sedentary men
      (age=21+/-3yrs; height=172+/-8cm; weight=66+/-9kg; VO2 max=37.6+/-7.4mL*kgkg
      1*min-1) participated in a double-blind randomized experiment. Unstimulated whole
      saliva samples were collected before, immediately and 1 hour after exhaustive
      treadmill running. Catalase, vitamin C (Vit C) concentration, and BDNF
      concentrations were determined using biochemical assays and ELISA respectively.
      Repeated measures ANOVA and Bonferroni posthoc test were used to analyze data.
      Results: The results of the present study showed that an acute intensive exercise
      causes a reduction in salivary catalase, Vit C and also BDNF concentration
      (p<0.05) compared with pre-exercise. Both catalase and Vit C showed a tendency to
      return to pre-exercise value after one hour. However, BDNF continued to reduction
      at least 1 hour after the ending of the training. Conclusion: Reduction in
      antioxidants capacity of saliva might reflects disturbance in natural antioxidant
      defense mechanisms of the body after an acute intensive physical stress and
      possible further health threatening consequences.

PMID- 28491828
TI  - The association between fear of falling and quality of life for balance
      impairments based on hip and ankle strategies in the drug On- and Off-phase of
      patients with idiopathic Parkinson' disease.
AB  - Background: Despite the negative effect of fear of falling during functioning and
      social participation of patients with Parkinson' disease, so far, only few
      studies have investigated its effect on the quality of life in these patients. We
      aimed to investigate the association between fear of falling and quality of life
      controlling for balance impairments based on hip and ankle strategy in drug On-
      and Off-phase of patients with idiopathic Parkinson' disease. Methods: In this
      non-experimental cross-sectional study, 139 patients with idiopathic Parkinson'
      disease (100 male, 39 female) by mean+/- SD age of 60.2+/-12.27 years, mean+/-SD
      time since diagnosis of 6.7+/-5.53 years and mean+/-SD Hoehn and Yahr stage of
      2.8+/-1.49 were selected by a simple non-probability method. Balance function was
      measured by a functional reach test with hip and ankle strategy. The Persian
      version of the selfcompleted Fall Efficacy Scale-International and Parkinson's
      disease quality of life questionnaire was used to evaluate fear of falling and
      quality of life, respectively. Results: The results showed that the score of all
      dimensions of quality of life (i.e., mobility, activities of daily living,
      emotional wellbeing, stigma, social support, cognition, communication and bodily
      discomfort) were significantly affected by the intensity of fear of falling.
      Multiple regression analysis indicated a significant association between fear of
      falling and quality of life in a way that fear of falling explained 11% to 47%
      and 12% to 43% of variance in drug On-phase, as well as 8% to 45% and 9% to 48%
      of variance in the drug Off-phase in dimensions of quality of life after
      controlling for balance function based on hip and ankle strategy, respectively.
      In the drug On-phase, the strongest association (R=0.85, p<0.001) was found
      between fear of falling and mobility dimension of quality of life. In the drug
      Off-phase, the strongest relation was observed between fear of falling and
      mobility (R=0.82, p<0.001) as well as activities of daily living (R=0.78-0.79,
      p<0.001) dimensions. Conclusion: This study found that fear of falling affects
      the quality of life of patients with Parkinson' disease beyond its relationship
      with balance impairments based on the hip and ankle strategy in both drug On- and
      Off-phase.

PMID- 28491829
TI  - Assessment of nutritional status in patients with Parkinson's disease and its
      relationship with severity of the disease.
AB  - Background: Malnutrition, loss of body weight, muscle and fat mass wasting are
      common in patients with Parkinson's disease, and are associated with disability,
      longer length of hospital stay, impaired immune system and increased risk of
      mortality. The aim of this study was to assess the nutritional status in patients
      with Parkinson's disease and its relation to the severity of the disease.
      Methods: This cross- sectional study was conducted on 130 patients with
      Parkinson's disease, with a mean (SD) age of 59.1 (12.9) years in disease stages
      of 1 to 4. In this study, the Mini Nutritional Assessment (MNA) questionnaire was
      used along with anthropometric measurements (Body Mass Index (BMI), Mid-arm
      circumference (MAC), Calf Circumference (CC)) to evaluate the nutritional status,
      and they were applied by a trained nutritionist. Hoehn and Yahr Scale were used
      to determine the severity of the disease. One-way ANOVA test was used to assess
      the relationship between anthropometric indices, nutritional status and severity
      of disease. Assessment of the relationship between age, duration of disease and
      nutritional status was categorized according to MNA score, and was performed,
      using one-way ANOVA. Chi - Square test was utilized to assess the relationship
      between education level and nutritional status. SPSS Version 18 was used for data
      analysis. Results: In this study, 30% (n=39) of the participants were diagnosed
      with normal nutritional status, 58.5% (n=76) were at risk of malnutrition and
      11.5% (n=15) were malnourished according to MNA. Reduction of weight, and muscle
      mass wasting was observed in different disease stages. Muscle mass wasting and
      worsening nutritional status, based on MNA score, showed a significant increase
      as the disease progressed, MAC (p=0.009), MNA score (p<0.001). After assessing
      the relationship between education level, age, duration of disease with
      nutritional status, the results revealed a significant relationship between age
      (p=0.008), education level (p<0.001) with nutritional status according to MNA
      score. Conclusion: Reduction of BMI, depletion of muscle mass, and worsening of
      nutritional status according to MNA, was observed in many patients along with an
      increase in the severity of the disease. Assessing nutritional status in those
      with Parkinson's disease to provide information to identify necessary nutritional
      intervention is highly recommended.

PMID- 28491830
TI  - Designing and assessing fixed dental prostheses 2 multimedia-based education in
      dentistry students.
AB  - Background: Above all methods effective learning results from decent training,
      acquired in the proper environment and encouraging creative methods. Computer
      assisted training by educational software is considered a fundamental measure to
      improve medical and dentistry education systems. This study aims to design and
      assess fixed dental prostheses via 2 multimedia instructional contents at the
      Guilan dentistry school. Methods: This is a descriptive and cross-sectional
      study. First off, the instructional content was analyzed. The software used to
      produce multimedia was the iSpring suite Ver.7.0. After designing the
      instructional multimedia, this software was loaded by LMS. Sixty-nine dentistry
      students in the 5th semester at Guilan Dentistry School were selected via
      convenience sampling. At the end of the course, a structured questionnaire
      containing 26 items were handed to the students to evaluate the instructional
      multimedia quality. Results: Mean +/-SD age was 24.68+/-3.24 years, 43 were women
      (62.4%) and 26 were men (37.6%) -the majority of 76.8% used the internet at home.
      A portion of 33.3% were inclined to use multimedia and the internet with in
      person training. About 60% declared that multimedia quality as being good.
      Conclusion: the instructional multimedia designs which are compatible with lesson
      objectives and audiovisual facilities can have a great effect on the student's
      satisfaction. Preparing instructional multimedia makes the instructional content
      easily accessible for students to be able to review it several times at the
      proper opportunity and if presented through LMS they would be able to study the
      lesson subject wherever and whenever accessing the internet.

PMID- 28491831
TI  - The effect of an android-based application on the knowledge of the caregivers of
      children with cerebral palsy.
AB  - Background: Mobile health and e-learning may have a significant impact on
      training patients, physicians, students and caregivers. This study aimed to
      evaluate the effect of using an educational mobile application on the knowledge
      of the caregivers of children with cerebral palsy (CP). Methods: We used a
      previously developed mobile application. The knowledge of 17 caregivers of
      children with CP (including parents) about the daily care of their children was
      evaluated through a self-assessment and a test with multiple-choice and true
      false questions. Next, the application, which included several educational
      modules for the daily care of the children with CP, was given to the caregivers
      to use continually for two months. After this period, the knowledge of the
      caregivers was evaluated by the same tools. Data analysis was performed by SPSS
      16, using paired-sample t-test or Wilcoxon test. Results: The effect of the use
      of this educational application on the knowledge of caregivers in all childcare
      domains, except for eating, was reported to be significant (p<0.05). Furthermore,
      the results of the multiplechoice test revealed that this application increased
      the knowledge of caregivers in all domains except playing (p<0.05). Conclusion:
      Training through novel technologies such as Smartphone along with their
      applications can improve the knowledge of caregivers about the daily care of
      children with cerebral palsy.

PMID- 28491832
TI  - Factors influencing the adoption of E-learning in Tabriz University of Medical
      Sciences.
AB  - Background: Electronic Learning (E-learning), is the use of electronic technology
      in education via computer and the internet. Despite its slow adoption by faculty
      members, e-learning provides several benefits to individuals and organizations.
      This study was conducted to determine the factors influencing the adoption of e
      learning by faculty members in Tabriz University of Medical Sciences. Methods:
      This was a cross- sectional study, in which a sample of 190 faculty members of
      Tabriz University of Medical Sciences was randomly selected, using stratified
      sampling. A Conceptual Path Model of Unified Theory of Acceptance and Use of
      Technology (UTAUT) was applied to assess the faculty members' attitude towards e
      learning. The collected data were analyzed by SPSS16, using descriptive
      statistics and regression analysis. The model was tested by structural equation
      modeling (SEM) and was finally represented by Analysis of Moment Structures.
      Results: The results evidenced that UTAUT model explains about 56% of the
      variance for adoption of elearning. The findings also revealed that performance
      expectancy, effort expectancy, social influences and behavior indentation had
      direct and significant effects on faculty members' behavior towards the use of e
      learning. However, facilitated condition had no significant effects on the use of
      e-learning. Conclusion: The authorized model provides considerable insight for
      perception and anticipation of faculty members' behaviors in adopting e-learning.
      The survey clearly identified significant and non-significant factors that may
      affect the adoption of e-learning. The results of this study could help the
      policy makers when successful adoption of e-learning is in their agenda.

PMID- 28491833
TI  - Virtual in-service training from the librarians' point of view in libraries of
      medical sciences universities in Tehran.
AB  - Background: In-service training courses are one of the most available programs
      that are used to improve the quantity and quality level of the staff services in
      various organizations, including libraries and information centers. With the
      advent of new technologies in the field of education, the problems and
      shortcomings of traditional in-service training courses were replaced with
      virtual ones. This study aimed to evaluate the virtual in-service training
      courses from the librarians' point of view in libraries of state universities of
      medical sciences in Tehran. Methods: This was a descriptive- analytical study.
      The statistical population consisted of all librarians at libraries of
      universities of medical sciences in Tehran. Out of 103 librarians working in the
      libraries under the study, 93 (90%) participated in this study. Data were
      collected, using a questionnaire. Results: The results revealed that 94/6% of
      librarians were satisfied to participate in virtual in-service training courses.
      In this study, only 45 out of 93 participants said that the virtual in-service
      courses were held in their libraries. Of the participants, 75.6% were satisfied
      with the length of training courses, and one month seemed to be adequate time
      duration for the librarians to be more satisfied. The satisfaction level of the
      individuals who participated in in-service courses of the National Library was
      moderate to high. A total of 84.4% participants announced that the productivity
      level of the training courses was moderate to high. The most important problem
      with which the librarians were confronted in virtual in-service training was the
      "low speed of the internet and inadequate computer substructures". Conclusion:
      Effectiveness of in-service training courses from librarians' point of view was
      at an optimal level in the studied libraries.

PMID- 28491834
TI  - systematized review of telemedicine applications in treating burn patients.
AB  - Background: Telemedicine has been used in different fields of medicine in the
      past 20 years. The main advantages of this technology include saving costs,
      improving quality of care, and increasing access to specialists. This study aimed
      to review telemedicine applications in treating burn patients. Methods: In this
      systematized review study, related papers were searched using various databases,
      including PubMed, Scopus, and Science Direct. The time frame was between January
      2000 and March 2016; finally, 32 papers were included in the study. Results: The
      findings revealed that telemedicine was used in burn care in three different
      ways: Remote patient follow-up, teleconsultation, and patient assessment.
      Conclusion: It seems that telemedicine can be easily applied in treating burn
      patients even when there is a limited financial resource. The use of this
      technology can help reduce possible errors in categorizing burn patients and
      decrease patients' transportation and treatment costs.

PMID- 28491835
TI  - Evaluation of the learning management system using students' perceptions.
AB  - Background: Learning Management System (LMS) is a web-based system designed to
      support teaching and learning at an institution. The capabilities of any LMS are
      required to be evaluated to detect the room for improvement. This study aimed at
      discovering the students' perceptions of the functions of the LMS at Iran
      University of Medical Sciences (IUMS). Methods: This qualitative study included
      15 students of two master programs of Biostatistics and Medical Librarianship
      during the fall semester of 2015. The participants were asked to write down their
      perceptions of the experiences they had while using the LMS and classify them
      based on two categories of "Advantages and Drawbacks". Framework Analysis
      technique was used to analyze the views. Results: The themes emerging from the
      'Advantages' included advantages for the students, advantages for the teachers,
      and advantages for both; however, those from the 'Drawbacks' were found to be
      technical and nontechnical problems. Conclusion: The major debated points in the
      comments comprised the students' positive accounts of the Forum section, and
      their complaints of the frequent glitches recurring in the system as well as some
      constructive problems such as inefficient tools for typing in English. Some all
      inclusive inferences concerning the methodology of the study have also been
      pointed out in the final section.

PMID- 28491836
TI  - Three-dimensional simulation of human teeth and its application in dental
      education and research.
AB  - Background: A comprehensive database, comprising geometry and properties of human
      teeth, is needed for dentistry education and dental research. The aim of this
      study was to create a three-dimensional model of human teeth to improve the
      dental E-learning and dental research. Methods: In this study, a cross-section
      picture of the three-dimensional model of the teeth was used. CT-Scan images were
      used in the first method. The space between the cross- sectional images was about
      200 to 500 micrometers. Hard tissue margin was detected in each image by Matlab
      (R2009b), as image processing software. The images were transferred to Solidworks
      2015 software. Tooth border curve was fitted on B-spline curves, using the least
      square-curve fitting algorithm. After transferring all curves for each tooth to
      Solidworks, the surface was created based on the surface fitting technique. This
      surface was meshed in Meshlab-v132 software, and the optimization of the surface
      was done based on the remeshing technique. The mechanical properties of the teeth
      were applied to the dental model. Results: This study presented a methodology for
      communication between CT-Scan images and the finite element and training software
      through which modeling and simulation of the teeth were performed. In this study,
      cross-sectional images were used for modeling. According to the findings, the
      cost and time were reduced compared to other studies. Conclusion: The three
      dimensional model method presented in this study facilitated the learning of the
      dental students and dentists. Based on the three-dimensional model proposed in
      this study, designing and manufacturing the implants and dental prosthesis are
      possible.

PMID- 28491837
TI  - Incorporating E-learning in teaching English language to medical students:
      exploring its potential contributions.
AB  - Background: The spread of technology has influenced different aspects of human
      life, and teaching and learning are not exceptions. This study aimed to examine
      the potential contribution of the use of technology in teaching English language
      to medical students. Methods: This qualitative-action research study was
      conducted in Birjand University of Medical Sciences (BUMS), with 60 medical
      students taking a general English course in the Fall Semester of 2015. The class
      favored different tools and multimedia facilities such as a tube channel, e
      dictionaries, educational films, and etextbooks to enhance students' learning. In
      addition, the class had a weblog in which students could upload assignments and
      receive feedback from peers and the instructors. Results: The results revealed
      that e-learning could enhance students' language proficiency and facilitate the
      teaching process. Learners preferred to use more e-dictionaries to learn the
      meaning of the new words, watch English medical films to boost their speaking and
      listening skills, and use the electronic version of their textbook as they could
      carry it wherever they wanted. Conclusion: The students preferred this method of
      learning English as they became more independent by using the electronic
      facilities. They found that learning English did not have a fixed
      institutionalized method, and e-learning activities could provide them with
      authentic input for language learning even outside of the classroom.

PMID- 28491838
TI  - The essential skills required by librarians to support medical virtual learning
      programs.
AB  - Background: With the recent spread of virtual learning programs in universities,
      especially in the field of medical sciences, libraries play a crucial role to
      support these programs. This study aimed at investigating the skills required by
      librarians to support virtual learning programs in Isfahan University and Isfahan
      University of Medical Sciences. Methods: This was an applied survey study. The
      population of the study includes all librarians working in Isfahan University and
      Isfahan University of Medical Sciences. A sample of 89 librarians was selected by
      stratified random sampling. Data were collected by a researcher-made
      questionnaire, the validity of which was confirmed by specialists in the fields
      of librarianship and information sciences and virtual learning, and its
      reliability was determined to be 0.92, using Cronbach's Alpha. The questionnaire
      consisted of 51 items designed to evaluate the librarians' virtual learning
      skills using Likert scale. Descriptive and inferential statistics were used to
      analyze the findings. Results: The findings of this study revealed that
      librarians had low level of skills with respect to the online reference services,
      and familiarity with virtual learning environment. They also showed low and
      average level of skills with respect to their general information technology,
      communication skills, ability to teach electronic information literacy and
      ability to create access to electronic resources. The results revealed no
      significant difference between the librarians of the two universities, or between
      male and female librarians. However, librarians with educational background in
      librarianship and information sciences were significantly more skillful and
      competent than their colleagues. Conclusion: Despite the crucial role of
      libraries in supporting virtual learning programs, the librarians in Isfahan
      University and Isfahan University of Medical Sciences had low-level skills to
      play such an important role. Therefore, it is essential to provide on-the-job
      virtual training courses for librarians to improve their job performance and the
      quality of library services.

PMID- 28491839
TI  - Online survey software as a data collection tool for medical education: A case
      study on lesson plan assessment.
AB  - Background: There are no general strategies or tools to evaluate daily lesson
      plans; however, assessments conducted using traditional methods usually include
      course plans. This study aimed to evaluate the strengths and weaknesses of online
      survey software in collecting data on education in medical fields and the
      application of such softwares to evaluate students' views and modification of
      lesson plans. Methods: After investigating the available online survey software,
      esurveypro was selected for assessing daily lesson plans. After using the
      software for one semester, a questionnaire was prepared to assess the advantages
      and disadvantages of this method and students' views in a cross-sectional study.
      Results: The majority of the students (51.7%) rated the evaluation of classes per
      session (lesson plans) using the online survey as useful or very useful. About
      51% (n=36) of the students considered this method effective in improving the
      management of each session, 67.1% (n=47) considered it effective in improving the
      management of sessions for the next semester, and 51.4% (n=36) said it had a high
      impact on improving the educational content of subsequent sessions. Finally,
      61.4% (n=43) students expressed high and very high levels of satisfaction with
      using an online survey at each session. Conclusion: The use of online surveys may
      be appropriate to improve lesson plans and educational planning at different
      levels. This method can be used for other evaluations and for assessing people's
      opinions at different levels of an educational system.

PMID- 28491840
TI  - The relationship between hospital managers' leadership style and effectiveness
      with passing managerial training courses.
AB  - Background: Effective leadership that rises from managerial training courses is
      highly constructive in managing hospitals more effectively. This study aims at
      investigating the relationship between leadership effectiveness with providing
      management training courses for hospital managers. Methods: This was a cross
      sectional study carried out on top and middle managers of 16 hospitals of Iran
      University of Medical Sciences. As a sample, 96 participants were selected
      through census method. Data were collected using leadership effectiveness and
      style questionnaire, whose validity and reliability were certified in previous
      studies. Pearson correlation coefficient and linear regressions were used for
      data analysis. Results: Leadership effectiveness score was estimated to be 4.36,
      showing a suitable status for managers' leadership effectiveness compared to the
      set criteria. No significant difference was found between leadership
      effectiveness and styles among managers who had passed the training courses with
      those who had not (p>0.05). Conclusion: Passing managerial training courses may
      have no significant effect on managers' leadership effectiveness, but there may
      be some other variables which should be meticulously studied.

PMID- 28491841
TI  - The effect of foot hyperpronation on spine alignment in standing position.
AB  - Background: According to clinical observations, foot hyperpronation is very
      prevalent and may cause malalignment of the lower extremity, leading to
      structural and functional deficits in standing and walking. This study aimed at
      investigating the effect of foot hyperpronation on spine alignment in the
      standing position. Methods: Thirty-five healthy males with an age range of 18-30
      years participated in this cross-sectional study. Evaluation was performed with
      two examiners in four standing positions (on the floor, and on the wedges angled
      at 10, 15, and 20 degrees) using a motion analysis system (Zebris). Moreover,
      each of the measurement methods was repeated for three short times. Paired t-
      test and repeated measures ANOVA test were used for statistical analysis.
      Results: Significant differences were observed between all modes in the sacral
      angle, pelvic inclination, lumbar lordosis, and thoracic kyphosis variables
      (except between the first and second mode). Finally, a positive correlation was
      obtained for the examiners and all the variables with an increasing slope of the
      angle of wedge. Conclusion: The results of the present study revealed sacral
      angle, pelvic inclination, lumbar lordosis, and thoracic kyphosis were increased
      with an increase in bilateral foot pronation. In fact, each one of them is a
      compensatory phenomenon.

PMID- 28491842
TI  - Ergonomic risk factors and musculoskeletal symptoms in surgeons with three types
      of surgery: Open, laparoscopic, and microsurgery.
AB  - Background: Musculoskeletal symptoms are the main cause of loss of working time,
      and increase in labor costs. Poor posture is the most important risk factor for
      work-related musculoskeletal symptoms. This study aimed at evaluating the role of
      ergonomic risk factors in different surgical (open surgery, laparoscopy, and
      microsurgery) in the frequency or resonance frequency of musculoskeletal
      symptoms. Methods: This descriptive-analytic study was conducted on 81 surgeons
      in a hospital in Tehran. In this study, the prevalence of musculoskeletal
      symptoms was evaluated using the Nordic Questionnaire. Moreover, Workplace
      ergonomic risk assessment method (WERA) was used to evaluate ergonomic risk
      factors in 3 types of open surgery, laparoscopy, and microsurgery. Results: The
      results revealed that the prevalence of musculoskeletal symptoms of the neck,
      back, shoulder, and arm is high in surgeons (over 75%). The mean final score of
      WERA was 40.11, representing the high risk of the 3 types of surgery for the
      prevalence of musculoskeletal symptoms. Results revealed that the prevalence of
      musculoskeletal symptoms in the neck, waist and wrists had a significant
      relationship with the body posture in the 3 types of open surgery, laparoscopy,
      and microsurgery (p<0.05). Conclusion: In the present study, the prevalence of
      musculoskeletal symptoms was high in the neck, waist, and hands surgeries.
      Depending on the type of surgery, teaching correct working methods, using proper
      seats and ergonomic equipment are the best strategies to reduce musculoskeletal
      symptoms in the surgical profession.

PMID- 28491843
TI  - Evaluation of occupational allergic contact dermatitis and its related factors in
      Iran.
AB  - Background: Occupational contact dermatitis, especially in hand, is one of the
      most common occupational disorders. The present study aimed at evaluating
      patients with occupational allergic contact dermatitis (ACD) caused by common
      allergens based on occupation type and disease history. Methods: This cross
      sectional study aimed at evaluating the data of the patients with probable
      diagnosis of ACD in Center for Research and Training in Skin Diseases and Leprosy
      (CRTSDL) in Iran. In the present study, 946 patients were assessed from different
      regions of Iran. One hundred fifty-one cases with positive patch test and
      relevant exposure were entered into the study; data related to their occupation
      and disease activity history were evaluated and recorded. Then, factors related
      to disease activity history were assessed considering the occupational groups and
      common exposures. Results: Nickel sulphate was the most common allergen in the
      151 patients. Disease activity was constant in 29.8% of the patients; it
      increased in 27.8%, and decreased just before doing the patch test in 42.4%. Of
      the patients, 52.3% were getting worse during the working days. Occupational
      groups were significantly different in age and gender. Disease duration was also
      different in the occupational groups (p=0.001). The least disease duration was
      observed in healthcare workers, and the most in service workers. Lesions in the
      foot were related to period of employment. In administrative work group,
      (teachers, technicians and housewives) disease activity was decreased in the most
      cases, while it was increased in most patients of service workers (p=0.086).
      Conclusion: The present study, similar to previous reports, revealed that nickel
      sulphate is the most common allergen in ACD cases. Moreover, it was found that
      the symptoms of disease activity remained constant or increased in a significant
      proportion of the cases during the working days. Therefore, these workers should
      seriously follow up on this matter and change their occupation, or limit the
      exposure to allergens.

PMID- 28491844
TI  - Factors associated with the severity of fatal accidents in construction workers.
AB  - Background: Construction work (building houses, roads, workplaces, and repairing
      and maintaining infrastructures) is a dangerous land-based job. This includes
      many hazardous tasks and conditions such as working at the following conditions:
      Height, excavation, noise, dust, power tools and equipment. Construction work has
      been increased in developed and underdeveloped countries over the past few years.
      Occupational fatalities have increased with an increase in this type of work.
      Occupational fatalities refer to individuals who pass way while on the job or
      performing work related tasks. In the present study, to identify the factors,
      personal characteristics and work-related factors associated with fatal
      occupational mortality were assessed using data for Tehran, Iran, 2014-2016.
      Methods: We conducted a retrospective study, using 967 postmortem reports from
      fatal occupational injuries collected through postmortem investigations during
      2014-2016. A sampling frame of 967 postmortem reports from fatal occupational
      injuries was used to draw a total sample of 714 fatal construction accidents for
      this cross-sectional study. Pearson chi2 test and Kruskal-Wallis tests were used
      for statistical analysis. Results: Based on the results of this study, male
      gender (n=714; 100%), age range of 30-39 years (n=183; 25.6%), secondary
      educational level (n=273; 38.2%), being married (317; 44.4%), causal employee
      (n=389; 54.5%), unskilled performance (389; 54.5%), no insurance coverage (472;
      66.1%), and daytime duty work (287; 40.2%) were identified as risk factors for
      fatality in the event of construction fatal injury. A significant relationship
      was found between the type of injury and sociodemographic and work related
      variables. Conclusion: Workers' characteristics such as age, gender, experience,
      and educational background, and work related variables such as skill training,
      safety measurement, and close monitoring could be used to discriminate among
      different severity levels of occupational fatal accidents.

PMID- 28491845
TI  - The role of work- related physical and psychological factors on prevalence of
      neck/shoulder complaints among nurses: A multicentric study.
AB  - Background: Identifying the predisposing factors of neck and shoulder complaints
      and finding solutions to avoid them could improve the occupational health
      condition of the nurses. In this study, we aimed at determining the role of
      psychological and physical occupational factors in developing neck and shoulder
      complaints among the participants. Methods: This analytic cross-sectional study
      was conducted on the nurses of main hospitals of Tehran. To study the prevalence
      of neck and shoulder pain, the Nordic questionnaire was used, and job content
      questionnaire was used to assess the psychological and physical occupational
      factors. Data were analyzed using SPSS and statistical methods. Independent
      sample t-test was used to compare the qualitative variables, and chi-square test
      was utilized for the statistical analysis of the qualitative variables. Results:
      Prevalence of neck and shoulder complaints among the nurses with high physical
      workload was significantly higher than in those nurses with low physical
      workload. Unlike physical workload, the prevalence of neck and shoulder
      complaints was not significantly different between the nurses with low or high
      psychological workload. Prevalence of neck and shoulder complaints among the
      female nurses was significantly higher than in the male nurses. In our study,
      only female nurses with high physical workload had been known as independent
      predictors of neck and shoulder complaints. Conclusion: Those nurses who had more
      workload, especially physical workload, had a higher prevalence of neck and
      shoulder complaints, and this fact could affect their work tasks.

PMID- 28491846
TI  - The effect of work- related stress on development of neck and shoulder complaints
      among nurses in one tertiary hospital in Iran.
AB  - Background: There are some challenges about the role of work- related stress on
      development of musculoskeletal complaints. The present prospective study was
      conducted on nurses of Milad hospital in Tehran (Iran) to assess the role of work
      related stress on development of neck and shoulder pain among nurses. Methods:
      From the 1,900 nurses who completed the registry forms, 1,450 nurses met the
      inclusion criteria. We divided the participants into exposed and unexposed groups
      according to their DASS-21 scores. We collected the data of neck and shoulder
      pain among the nurses at two points of the first and the second year after the
      study, using the Nordic Questionnaire. Qualitative and quantitative variables
      were compared between the exposed and unexposed variables with chi-square and
      independent sample t-test, respectively. Results: One year after the commencement
      of the study, 62 (9.1%) nurses in the exposed group and 36 (4.7%) in the
      unexposed group had been reported as new cases of neck and shoulder pain,
      respectively. The incidence of the new cases of neck and shoulder pain was
      significantly higher in the exposed group compared to the unexposed group (p=
      0.001). Two years after the start of the study, at the second follow-up point,
      135 (19.8%) nurses in the exposed group and 76 (9.9%) in the unexposed group had
      been reported as new cases of neck and shoulder pain, respectively. The incidence
      of new cases of neck and shoulder pain was significantly higher in the exposed
      group compared to the unexposed group (p<0.001). Conclusions: The incidence of
      neck and shoulder pain was higher in those nurses with high level of workrelated
      stress. According to our results, more attention should be paid to mental health
      as well as physical symptoms and limitations of the healthcare workers when they
      refer to occupational health services with musculoskeletal pain complaints.

PMID- 28491847
TI  - The effect of a multifaceted ergonomic intervention program on reducing
      musculoskeletal disorders in dentists.
AB  - Background: Work-related musculoskeletal disorders (WMSDs) are the most common
      occupational injuries in dentists. These disorders occur due to the specific
      characteristics of dentistry occupation such as the use of tools and instruments
      and awkward posture. The present study aimed at evaluating the effect of
      multifaceted ergonomic program on reducing musculoskeletal disorders in dentists.
      Methods: One hundred-two male dentists who worked in dentistry clinics of
      Tehran's hospitals participated in this interventional study. Participants were
      randomly divided into control (n=50) and intervention (n=52) groups. Dentists in
      the intervention group (n=52) underwent multifaceted ergonomic intervention
      program for 8 weeks and dentists in the control group (n=50) only received the
      measurements. The prevalence of musculoskeletal disorders was evaluated in each
      of the 2 groups at 3 time points before the intervention, 3, and 6 months after
      the intervention using the Nordic Musculoskeletal Questionnaire (NMQ). Paired t
      test was used to compare the prevalence of musculoskeletal disorders before and
      after the ergonomic intervention program at the end of 3 and 6 months. Results:
      The results revealed that the prevalence of musculoskeletal disorders was reduced
      after the intervention in the neck, shoulder, arm, wrist, back, thigh, knees, and
      feet (p<0.05). On the other hand, the prevalence of musculoskeletal disorders
      increased in the control group in the neck, shoulder, arm, wrist, thigh, and
      knee, respectively. The survey results revealed that 98% of the participants
      agreed with this intervention program. Conclusion: The results of this study
      revealed that the multifaceted ergonomic intervention program, which included
      improving working conditions, identifying ergonomic risk factors, regular
      exercise, and discussion group meetings, could decrease the prevalence of
      musculoskeletal disorders in dentists.

PMID- 28491848
TI  - The effect of magnification lenses on reducing musculoskeletal discomfort among
      dentists.
AB  - Background: Work-related musculoskeletal disorders are the most important
      problems in the health workforce. These discomforts cause many working days
      losses, increase absenteeism from work, and impose annual economic costs. Awkward
      posture is the most important factor among the risk factors for work-related
      musculoskeletal disorders. This study aimed at implementing an interventional
      ergonomic program to minimize musculoskeletal disorder among dentists. Methods:
      This semi- experimental study was conducted on 75 dentists of Milad hospital
      using a census method. The Nordic Questionnaire was used to determine the
      prevalence of musculoskeletal disorders. In this study, the intervention was to
      apply optical magnification lens whose impact on reducing musculoskeletal
      disorder had been previously investigated. Corlett and Bishop Scale was used to
      evaluate musculoskeletal disorders before and after the intervention. Paired t
      test was conducted to compare the discomfort intensity before and after the
      intervention. Results: The results revealed that the prevalence of
      musculoskeletal disorders in neck, back, shoulder, and arm were higher than other
      areas of the body in dentists. There was a significant difference in discomfort
      intensity of the neck, shoulder, arm, back, elbow, forearm, and the whole body
      after the ergonomic intervention (p<0.05). Surveys on improving working
      conditions using the magnification lens revealed that more than 89% of the
      individuals expressed that the use of the lens increased the ease while working.
      Conclusion: The present study revealed that the use of optical magnification
      loupes, because of providing a suitable posture while working, could reduce
      musculoskeletal disorders in different areas of the body. Thus, we can predict
      that the prevalence of musculoskeletal disorders will be reduced in dentists in a
      long run if they use optical magnification loupes.

PMID- 28491849
TI  - Work-related stress and quality of life among Iranian blue-collar workers with
      self-reported low back pain.
AB  - Background: Impairment in quality of life and mental health had been reported in
      the previous studies as the results of musculoskeletal disorders among workers.
      Mental health has a wide concept and contains different disorders including
      anxiety, depression or even decreased quality of life, all of which having
      challengeable impacts on work- related characters such as work productivity and
      absensism. The present study aimed at evaluating work- related stress and quality
      of life among Iranian blue-collar workers of Fars ABFA Company with selfreported
      low back pain. Methods: In the present study, we focused on the low back pain
      among 451 blue-collar workers and assessed their work- related stress and quality
      of life status using DASS-21 and short form questionnaire (SF-36), respectively.
      Independent sample t-test was used to compare the qualitative variables, and chi
      square test was utilized for statistical analysis of the qualitative variables.
      Results: Mean of the total score of quality of life among workers with low back
      pain was significantly lower than in those workers without low back pain. The
      mean of work- related stress score was significantly higher in workers with low
      back pain than in workers without low back pain. The mean quality of life
      subdomains in patients with low back pain was significantly lower than in workers
      without low back pain. Conclusion: Findings of the present study revealed that
      workers with low back pain had lower quality of life score and higher work-
      related stress score. These findings should be considered in designing preventive
      programs rather than controlling the pain.

PMID- 28491850
TI  - MicroRNAs as biomarkers associated with bladder cancer.
AB  - Bladder cancer is the fifth most common cancer with significant morbidity and
      mortality. Recently, numerous studies demonstrated that microRNAs are emerging as
      diagnostic biomarkers for bladder cancer. Specific miRNA profiles have been
      identified for several samples from patients with bladder cancer. MicroRNAs are
      noncoding RNA molecules of approximately 23 nucleotides that play important roles
      in multiple steps during the progression of bladder cancer. Here, we review the
      expression profiles of miRNAs and their biological functions, regulation, and
      clinical implications in bladder cancer. Either downregulation or upregulation of
      miRNAs occurs in bladder cancer through epigenetic changes or defects of the
      biogenesis apparatus. Deregulation of miRNAs is involved in cell cycle arrest,
      apoptosis, proliferation, metastasis, drug resistance, and other functions in
      bladder cancer. A number of miRNAs, have been associated with tumor type, stage,
      or patient survival, and miRNAs might be developed as diagnostic or prognostic
      markers. A better understanding of the roles of miRNAs in bladder cancer will
      shed light on the molecular mechanisms of bladder cancer.

PMID- 28491851
TI  - Pemetrexed-induced acute kidney failure following irreversible renal damage: two
      case reports and literature review.
AB  - BACKGROUND: Pemetrexed (PEM) is a new-generation multitargeted antifolate agent
      with a demonstrated broad-spectrum activity in several types of human cancers,
      including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects
      include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known;
      however, its frequency is considered to be low. CASE PRESENTATION: Here we report
      two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2)
      in patients with NSCLC. The first patient required hemodialysis treatment and was
      submitted to renal biopsy which showed acute tubular damage and interstitial
      edema without acute tubular necrosis. No other potential nephrotoxic agents were
      identified. The second patient developed AKI, not proven by biopsy and did not
      require renal replacement therapy. Both patients, on regular supplementation with
      folic acid and vitamin B12, concomitantly developed myelosuppression and even
      several months after PEM withdrawal, showed only a modest improvement of renal
      function. CONCLUSIONS: PEM is an antifolate antineoplastic agent with a broad
      spectrum activity in locally advanced or metastatic NSCLC. It has been shown that
      PEM allows longer survival. The risk of acute or chronic kidney disease may be
      one of the prices to be paid for this success.

PMID- 28491852
TI  - A case of recurrent hematuria in primary prostatic low grade mucosa associated
      lymphoid tissue.
AB  - BACKGROUND: Primary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare
      malignancy. We found only 8 cases of MALT lymphoma in literature. CASE
      PRESENTATION: We report here another case of primary prostatic MALT lymphoma
      which is presented by hematuria and diagnosed primarily as BPH.
      Immunohistochemistry studies demonstrate the diagnosis and MALT lymphoma. Six
      months after starting the treatment the patient was alive and well. CONCLUSIONS:
      Prostatic MALTomas are mainly presented with urinary obstruction or hematuria and
      have an indolent growth with a good prognosis.

PMID- 28491853
TI  - Infection associated acute interstitial nephritis; a case report.
AB  - BACKGROUND: Acute interstitial nephritis (AIN) is a clinico-pathological syndrome
      associated with a variety of infections, drugs, and sometimes with unknown
      causes. It is a common cause of acute kidney injury (AKI) and subsequent renal
      impairment, which often times is under-diagnosed. Infection-associated AIN occurs
      as a consequence of many systemic bacterial, viral, and parasitic infec-tions;
      however, its incidence has decreased significantly after the advent of
      antimicrobials. Infection-associated AIN presents with both oliguric or non
      oliguric renal insufficiency, without the classical clinical triad of AIN (fever,
      rash, and arthralgia). In this scenario the renal function is usually reversible
      after the infection is treated. In most cases, patients with acute renal failure
      present with extra-renal manifestations typically detected in underlying
      infections. Renal biopsy serves as the most definitive test for both the
      diagnosis and prognosis of AIN. CASE PRESENTATION: In this paper, we will address
      one such case of biopsy-proven AIN. In this case, the patient presented with
      severe AKI induced by anaerobic streptococcus, leading to a periodontal abscess,
      which was successfully treated with corticosteroids and requiring renal
      replacement therapy (RRT). CONCLUSIONS: AIN should be considered in the
      differential for unexplained AKI. Initial management should include conservative
      therapy by withdrawing any suspected causative agent. Renal biopsy is needed for
      confirmation in cases where kidney function fails to improve within 5-7 days on
      conservative therapy. Risk of immunosuppression is very important to consider
      when giving steroids in patients with infection induced AIN, and steroids may
      have to be delayed until the active infection is completely controlled.

PMID- 28491854
TI  - MPO-ANCA-associated necrotizing glomerulonephritis in rheumatoid arthritis; a
      case report and review of literature.
AB  - BACKGROUND: Renal involvement in rheumatoid arthritis (RA) is common and has a
      negative impact on patient survival. Only few cases have been reported of
      necrotizing glomerulonephritis (GN) associated with myeloperoxidase anti
      neutrophil cytoplasmic antibody (MPO-ANCA) in patients with RA. CASE
      PRESENTATION: We report a patient with RA who developed a necrotizing GN
      associated with ANCA-MPO, treated with rituximab (RTX). A 55-year-old man with a
      27-year history of RA under secukinumab was referred to our nephrology clinic
      with worsening renal function associated with microhematuria and proteinuria. Our
      laboratory evaluation showed hypocomplementemia and positive titers for MPO-ANCA
      (615 U/mL). A renal biopsy demonstrated pauci-immune necrotizing GN. The patient
      was treated with 3 consecutive pulses of methylprednisolone followed by oral
      prednisolone (1 mg/Kg) and rituximab (1000 mg, repeated 14 days later). After a
      10-month follow-up, the arthritis remains well-controlled, renal function
      stabilized, proteinuria improved and MPO-ANCA titer normalized (6.3 U/mL).
      CONCLUSIONS: Necrotizing GN is a rare but a serious condition and an early
      diagnosis is essential to treatment. This is the first case of necrotizing GN
      (without extra-renal manifestations of vasculitis) in a patient with active RA,
      successfully treated with RTX.

PMID- 28491855
TI  - Nephrolithiasis in elderly population; effect of demographic characteristics.
AB  - BACKGROUND: Kidney stone (nephrolithiasis) is one of the most common diseases.
      During the past several decades, its prevalence and incidence have increased
      markedly in elderly population. OBJECTIVES: This study was conducted to evaluate
      the risk factors for nephrolithiasis in elderly population. PATIENTS AND METHODS:
      This study was based on the Amirkola Health and Ageing Project (AHAP). Elderly
      people with kidney stones in every size, type and number were considered to be
      the case group and other subjects without a history of kidney stones served as
      control group. Demographic and anthropometric data, smoking, diabetes and
      metabolic syndrome (MetS), calcium (Ca), vitamin D, parathyroid hormone (PTH),
      uric acid and urine pH were compared in both groups. RESULTS: In this study, 1390
      elderly people with the mean age of 69.37 +/- 7.42 years were evaluated which 202
      (14.53%) cases had renal stones. The patients with nephrolithiasis were younger
      (P = 0.010) and had higher uric acid and body mass index (BMI) levels (P = 0.041
      and P = 0.006, respectively). Age <75 years, male gender and BMI >=30 kg/m2 had a
      significant association with stone formation. The prevalence of diabetes, MetS
      and smoking in the patients with nephrolithiasis was lower than the subjects
      without it. CONCLUSIONS: This study suggests that male gender, obesity and age
      <75 years might be independent risk factors for the development of
      nephrolithiasis. Hence, low animal protein intake and weight reduction should be
      included as part of the counseling of senior stone-formers.

PMID- 28491856
TI  - Renal tissue pro-inflammatory gene expression is reduced by erythropoietin in
      rats subjected to hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock (HS) is a condition produced by considerable loss
      of intravascular volume, which may eventually lead to organ damage and death.
      OBJECTIVES: In the present study, the potential implication of the kidney tissue
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10
      (IL-10) were evaluated in the protective effects of erythropoietin (EPO) during
      HS. MATERIALS AND METHODS: Male Wistar rats were randomized into three
      experimental groups; Sham, HS (hemorrhagic shock and resuscitation), and EPO
      (erythropoietin). HS was induced by 50% blood volume hemorrhage over 30 minutes.
      After 2 hours, resuscitation was performed within 30 minutes. In the EPO group,
      EPO (300 IU/kg, i.v.) was administered 10 minutes before HS induction. Urine was
      collected to determine urinary N-acetyl-beta-D-glucosaminidase (NAG) activity
      level. The kidney cytokines (TNF-alpha, IL-6 and IL-10) mRNA expressions were
      measured by real-time polymerase chain reaction (PCR). RESULTS: HS rats showed
      significant increase in urinary NAG activity compared to the sham group. EPO
      significantly attenuated the rises in urinary NAG activity compared to the HS
      group. In the HS animals, renal TNF-alpha and IL-6 mRNA expressions increased
      whereas no difference was observed in IL-10 mRNA expression between the HS and
      sham groups. EPO was able to decrease renal TNF-alpha and IL-6 production and
      increase IL-10 mRNA expression. CONCLUSIONS: In this study, we demonstrated that
      EPO attenuates kidney damage in rats subjected to HS. The beneficial effects of
      EPO may be at least partly mediated by modifications in the inflammatory cascade.

PMID- 28491857
TI  - Administration of zinc against arsenic-induced nephrotoxicity during gestation
      and lactation in rat model.
AB  - BACKGROUND: Free radicals production by toxicity of arsenic (Ar) is most
      important in the nephrotoxicity. There is accumulating evidence that zinc (Zn),
      has anti-oxidant properties. OBJECTIVES: The aim of present study was to evaluate
      protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in
      rat pups during gestation and lactation. MATERIALS AND METHODS: Twenty-four adult
      pregnant wistar rats were randomly divided into four groups (n = 6). Group one
      was given vehicle only. Group two received Zn (ZnSO4) at 20 mg/kg/d. Group three
      received Ar at 5 mg/kg/d as sodium meta-arsenite. Group four received Ar + Zn at
      the same dose that mentioned in groups of two and three. At the end of the study,
      24 hours after the last treatment, samples were killed with overdose of sodium
      pentobarbital and kidneys were harvested for measuring malondialdehyde (MDA),
      glutathione (GSH) and histopathological assessment. RESULTS: The MDA level in
      kidney was increased in the Ar group, which was decreased after Zn administration
      in the Ar + Zn group. The GSH level in kidney was decreased in the Ar group,
      which were increased after Zn administration in the Ar + Zn group. Also, the
      histopathological changes which were detected in the Ar group attenuated after Zn
      consumption. CONCLUSIONS: Our findings suggested that administration of Zn during
      gestation and lactation could have protective and prevent effect in Ar-induced
      oxidative stress in kidney tissue.

PMID- 28491858
TI  - Clinical outcomes and quality of life in hemodialysis diabetic patients versus
      non-diabetics.
AB  - BACKGROUND: Diabetes is the leading cause of end stage renal disease (ESRD)
      worldwide. OBJECTIVES: We compared the clinical outcomes in diabetic patients on
      hemodialysis (HD) with non-diabetics. PATIENTS AND METHODS: Adult maintenance HD
      patients (N= 532) from 9 HD facilities were enrolled to this prospective cohort
      study in September 2012. Causes of death, hospitalization, and HD exit were
      recorded in a median 28 months follow up period. RESULTS: Forty-one percent of
      patients were diabetic. Diabetic patients compared to non-diabetics had
      significantly higher age (62.2 +/- 11.2 versus 53.1 +/- 16.7 years), lower
      dialysis duration (median: 23 versus 30 months), more cardiovascular
      comorbidities (64% versus 28%) , higher C-reactive protein (CRP) levels (median:
      3.80 versus 2.25 mg/L), lower serum albumin (3.86 +/- 0.35 versus 3.93 +/- 0.35
      g/dL), lower intact parathyroid hormone (iPTH) (median: 272 versus 374 rhog/mL),
      higher serum triglyceride (167 +/- 91 versus 139 +/- 67 mg/dL) and low density
      lipoprotein (LDL) (82.5 +/- 24.5 versus 77.5 +/- 23.8 mg/dL), and worse short
      form health survey (SF36) score (45.7 +/- 20.9 versus 52.7 +/- 20.5). Annual
      admission rate was higher in diabetics (median: 0.86 versus 0.43) and diabetic
      foot involved 16% of their admissions. Transplantation rate was 4 and 9 per 100
      patient years in diabetics and non-diabetics, respectively. Death rate was two
      folds higher in diabetics (24 versus 12 per 100 patient years). Cardiovascular
      diseases ( +/- infections/other causes) comprised 80.5% of death in diabetics and
      54.5% in non-diabetics. In Cox regression proportional hazard multivariate
      analysis, hazard risk of death in diabetics was 1.9 times higher than non
      diabetics. CONCLUSIONS: Clinical outcomes and health related quality of life
      (HRQOL) are much worse in diabetic compared to non-diabetic HD patients mainly
      due to more frequent of cardiovascular diseases (CVDs).

PMID- 28491859
TI  - Autophagy in kidney transplants of sirolimus treated recipients.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used
      as immunosuppressive agents in kidney transplantation. In the experimental
      setting it has been shown that mTOR inhibitors promote autophagy, but the concept
      that this might also occur in transplant patients has not been addressed.
      OBJECTIVES: This study was designed to investigate the association between mTOR
      inhibition and autophagy in renal transplants under routine clinical conditions.
      MATERIALS AND METHODS: Protocol transplant biopsies of patients receiving
      sirolimus were compared to biopsies of patients treated without mTOR inhibitor.
      Electron microscopy was used for quantitative stereological analysis of
      autophagosomal volume fractions. Ultrastructural analysis was focused on
      podocytes to avoid cell type bias. Autophagy-related gene products were profiled
      by QPCR from laser assisted microdissected glomeruli and by immunohistochemistry
      for semiquantitative evaluation. RESULTS: By electron microscopy, we observed a
      significant > 50% increase in podocytic autophagosomal volume fractions in
      patients treated with sirolimus. Evaluation of biopsy material from the same
      patients using transcriptional profiling of laser capture microdissected
      glomeruli revealed no differences in autophagy-related gene expressions.
      Immunohistochemical evaluation of autophagic degradation product p62 was also
      unaltered whereas a significant increase was observed in podocytic LC3 positivity
      in biopsies of sirolimus treated patients. CONCLUSIONS: These results indicate an
      association of sirolimus treatment and autophagosome formation in transplant
      patients. However, they might reflect autophagosomal buildup rather than
      increased autophagic flux. Further research is needed to investigate the
      potential functional consequences in short- and long-term outcome of patients
      treated with mTOR inhibitors.

PMID- 28491860
TI  - Differences in the frequency of macrophage and T cell markers between focal and
      crescentic classes of anti-neutrophil cytoplasmic antibody (ANCA)-associated
      glomerulonephritis.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated
      glomerulonephritis (AAGN) can be classified into; focal, crescentic, mixed and
      sclerotic classes. Macrophages and T lymphocytes are key players in mediating
      renal injury. The frequency of macrophage and T lymphocytes in different
      histological classes is unclear. OBJECTIVES: We examined the frequency of
      macrophage and T lymphocyte markers in AAGN and assessed their correlation with
      renal function at presentation. PATIENTS AND METHODS: Renal biopsies from 38
      patients were included in immunohistochemistry analysis of macrophages (CD68,
      sialoadhesin [Sn] and mannose receptor [MR]) and T cells (CD4 and CD8) markers.
      The frequency of these markers in glomerular, periglomerular and interstitial
      compartments were measured in a blinded fashion. Biopsies were allocated a
      histological class of focal, crescentic, mixed or sclerotic. Scores were then
      matched to histological class and assessed for correlation with renal function.
      RESULTS: The biopsies were crescentic 19 (50%), focal 10 (26.3%), mixed 6 (15.7%)
      and sclerotic 3 (8%). Interstitial CD68+ macrophages and CD8+ T lymphocytes
      showed best correlation with renal function at the time of presentation. CD68+
      macrophages were significantly increased in crescentic compared to focal AAGN.
      MR+ macrophages, CD4 and CD8 T cells were also elevated in the interstitium of
      crescentic compared to focal group. CONCLUSIONS: In this study interstitial CD68
      and CD8 showed the highest association with the renal function at presentation.
      Differences in the cellular infiltrate between focal and crescentic AAGN were
      related to CD68+ macrophages and to interstitial MR+ macrophages and T
      lymphocytes. Further studies are needed to assess these differences across all
      four histological categories.

PMID- 28491861
TI  - Enteric-coated and highly standardized cranberry extract reduces antibiotic and
      nonsteroidal anti-inflammatory drug use for urinary tract infections during
      radiotherapy for prostate carcinoma.
AB  - INTRODUCTION: Worldwide, bacterial resistance to antibiotic therapy is a major
      concern for the medical community. Antibiotic resistance mainly affects Gram
      negative bacteria that are an important cause of lower urinary tract infections
      (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs.
      Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic
      role of an enteric-coated, highly standardized cranberry extract (VO370(r)) in
      reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory
      drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was
      evaluated. METHODS: A total of 924 patients with prostate carcinoma treated by
      radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489)
      or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7
      weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney
      U test and Pearson's chi2 test. Primary endpoint was the number of patients with
      LUTI; secondary endpoints were incidence of recurrence, days of treatment with
      antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.
      RESULTS: The treatment was very well tolerated, and there were no serious side
      effects. All enrolled patients completed the study. Urinary infections were
      detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly
      standardized cranberry extract, while 107 of the 435 patients (24.6%) in the
      control group developed LUTIs (p=0.0001). A clear and significant reduction in
      urinary discomfort of ~50% was seen in treated subjects. The treatment also
      resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics.
      CONCLUSION: The enteric-coated, highly standardized cranberry extract could be
      used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic
      therapy in patients receiving pelvic irradiation for prostate cancer.

PMID- 28491862
TI  - Comparison of Fecal Calprotectin Methods for Predicting Relapse of Pediatric
      Inflammatory Bowel Disease.
AB  - Background. Pediatric inflammatory bowel disease (IBD) is on the rise worldwide.
      Endoscopies are necessary for IBD assessment but are invasive, expensive, and
      inconvenient. Recently, fecal calprotectin (FCal) was proposed as a noninvasive
      and specific marker of gut inflammation. We evaluated the analytical performance
      of three FCal assays and their clinical performance in predicting relapse in
      pediatric IBD. Methods. This study used 40 pediatric IBD and 40 random non-IBD
      patients' fecal samples. Two automated ELISAs (Buhlmann and PhiCal(r)
      Calprotectin-EIA) and an EliA (Phadia 250 EliA-Calprotectin) were used to
      evaluate the analytical performance. The clinical performance was assessed by
      PhiCal Calprotectin-EIA, EliA-Calprotectin, and Buhlmann immunochromatographic
      point-of-care test (POCT). Results. All assays displayed acceptable analytical
      performance below and above the medical decision cut-off [imprecision (CV < 10%
      intra-assay; <15% interassay); linearity (overall mean % deviation < 16.5%)]. The
      agreement with PhiCal Calprotectin-EIA was 100% and 78.6% for Buhlmann (95% CI,
      87.5-100; Kappa: 1) and EliA-Calprotectin (95% CI, 60.5-89.8; Kappa: 0.32),
      respectively, and 63.6% between Buhlmann and EliA-Calprotectin (95% CI, 46.6
      77.8; Kappa: 0.16). All assays evaluated had similar clinical performance [AUC:
      0.84 (EliA-Calprotectin); 0.83 (POCT and PhiCal Calprotectin-EIA)]. Conclusion.
      FCal levels determined using the same method and assay together with clinical
      history would be a noninvasive and useful tool in monitoring pediatric IBD.

PMID- 28491863
TI  - Reproducing Patient-Specific Hemodynamics in the Blalock-Taussig Circulation
      Using a Flexible Multi-Domain Simulation Framework: Applications for Optimal
      Shunt Design.
AB  - For babies born with hypoplastic left heart syndrome, several open-heart
      surgeries are required. During Stage I, a Norwood procedure is performed to
      construct an appropriate circulation to both the systemic and the pulmonary
      arteries. The pulmonary arteries receive flow from the systemic circulation,
      often using a Blalock-Taussig (BT) shunt between the innominate artery and the
      right pulmonary artery. This procedure causes significantly disturbed flow in the
      pulmonary arteries. In this study, we use computational hemodynamic simulations
      to demonstrate its capacity for examining the properties of the flow through and
      near the BT shunt. Initially, we construct a computational model which produces
      blood flow and pressure measurements matching the clinical magnetic resonance
      imaging (MRI) and catheterization data. Achieving this required us to determine
      the level of BT shunt occlusion; because the occlusion is below the MRI
      resolution, this information is difficult to recover without the aid of
      computational simulations. We determined that the shunt had undergone an
      effective diameter reduction of 22% since the time of surgery. Using the
      resulting geometric model, we show that we can computationally reproduce the
      clinical data. We, then, replace the BT shunt with a hypothetical alternative
      shunt design with a flare at the distal end. Investigation of the impact of the
      shunt design reveals that the flare can increase pulmonary pressure by as much as
      7% and flow by as much as 9% in the main pulmonary branches, which may be
      beneficial to the pulmonary circulation.

PMID- 28491864
TI  - Can Getting Enough Vitamin D during Pregnancy Reduce the Risk of Getting Asthma
      in Childhood?
AB  - The worldwide increase in asthma prevalence during the last decades and the re
      emergence of vitamin D deficiency in many populations hinted toward an underlying
      association between these two conditions. Since asthma is presented with high
      incidence in childhood and neonatal vitamin D stores depend on maternal vitamin
      levels, a possible programming effect of maternal vitamin D status during
      gestation was suggested. Observational and longitudinal studies on this subject
      led to inconclusive results with glimmer of positivity. In the randomized
      controlled clinical trials (RCTs) that followed, increased doses of vitamin D
      were tested in pregnant women being at high risk of having an asthmatic child.
      Although, the results of RCTs showed a potential association with asthma-related
      phenotypes rather than asthma per se, the low toxicity of vitamin D supplements
      make it tempting to speculate that pregnant women at a high risk of obtaining a
      child with asthma may be benefited, especially if they are vitamin D deficient.

PMID- 28491865
TI  - The Role of the Central Nervous System Microenvironment in Pediatric Acute
      Lymphoblastic Leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common cancer in children. While
      survival rates for ALL have improved, central nervous system (CNS) relapse
      remains a significant cause of treatment failure and treatment-related morbidity.
      Accordingly, there is a need to identify more efficacious and less toxic CNS
      directed leukemia therapies. Extensive research has demonstrated a critical role
      of the bone marrow (BM) microenvironment in leukemia development, maintenance,
      and chemoresistance. Moreover, therapies to disrupt mechanisms of BM
      microenvironment-mediated leukemia survival and chemoresistance represent new,
      promising approaches to cancer therapy. However, in direct contrast to the
      extensive knowledge of the BM microenvironment, the unique attributes of the CNS
      microenvironment that serve to make it a leukemia reservoir are not yet
      elucidated. Recent work has begun to define both the mechanisms by which leukemia
      cells migrate into the CNS and how components of the CNS influence leukemia
      biology to enhance survival, chemoresistance, and ultimately relapse. In addition
      to providing new insight into CNS relapse and leukemia biology, this area of
      investigation will potentially identify targetable mechanisms of leukemia
      chemoresistance and self-renewal unique to the CNS environment that will enhance
      both the durability and quality of the cure for ALL patients.

PMID- 28491866
TI  - Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation.
AB  - Cells of the airways are constantly exposed to environmental hazards including
      cigarette smoke, irritants, pathogens, and mechanical insults. Maintaining
      barrier integrity is vital, and mounting responses to threats depends on
      intercellular communication. Extracellular vesicles (EVs), including exosomes and
      microvesicles, are major signal mediators between cells, shuttling cargo in
      health and disease. Depending on the state of the originating cells, EVs are
      capable of inducing proinflammatory effects including antigen presentation,
      cellular migration, apoptosis induction, and inflammatory cytokine release. Cells
      of the airways release EVs, which can be found in bronchoalveolar lavage fluid.
      EVs of the airways can support inflammation in the lung, but may also exit into
      the circulation and carry a cocktail of pro-inflammatory molecules to recipient
      cells in distant organs. In this review, we discuss the possibility that EVs
      originating from the airways contribute to dissemination of inflammation in both
      lung disorders and systemic inflammatory conditions.

PMID- 28491868
TI  - FluoroType MTB system for the detection of pulmonary tuberculosis.
AB  - FluoroType MTB is a sensitive test for TB but specificity is low compared with
      fully integrated molecular systems http://ow.ly/WhEO30b1luY.

PMID- 28491869
TI  - Prevalence and Associated Factors of Suicidal Ideation and Attempt among People
      Living with HIV/AIDS at Zewditu Memorial Hospital, Addis Ababa, Ethiopia: A Cross
      Sectional Study.
AB  - Background. Human Immune Deficiency Virus (HIV/AIDS) continues to be an
      underrecognized risk for suicidal ideation, suicidal attempt, and completion of
      suicide. Suicidal ideation and attempt in HIV/AIDS is not only a predictor of
      future attempted suicide and completed suicide. Methods. An institution based
      cross-sectional study was conducted among HIV-positive patients attending HIV
      care at Zewditu Memorial Hospital. Systematic random sampling technique was used
      to recruit 423 participants from April to May 2014. Composite International
      Diagnostic Interview was used to collect data. Multivariable logistic regression
      was computed to assess factors associated with suicidal ideation and attempt.
      Result. Suicidal ideation and suicidal attempt were found to be 22.5% and 13.9%,
      respectively. WHO clinical stage of HIV, not being on HAART, depression, family
      history of suicidal attempt, and perceived stigma were associated with suicidal
      ideation. WHO clinical stage, being female, not being on HAART, use of substance,
      and depression were associated with suicidal attempt. Conclusion. Early diagnosis
      and treatment of opportunistic infections, depression, and early initiation of
      ART need to be encouraged in HIV-positive adults. Furthermore, counseling on
      substance use and its consequences and early identification of HIV-positive
      people with family history of suicidal ideation have to be considered.

PMID- 28491867
TI  - Metabolic Reprogramming in Glioma.
AB  - Many cancers have long been thought to primarily metabolize glucose for energy
      production-a phenomenon known as the Warburg Effect, after the classic studies of
      Otto Warburg in the early twentieth century. Yet cancer cells also utilize other
      substrates, such as amino acids and fatty acids, to produce raw materials for
      cellular maintenance and energetic currency to accomplish cellular tasks. The
      contribution of these substrates is increasingly appreciated in the context of
      glioma, the most common form of malignant brain tumor. Multiple catabolic
      pathways are used for energy production within glioma cells, and are linked in
      many ways to anabolic pathways supporting cellular function. For example:
      glycolysis both supports energy production and provides carbon skeletons for the
      synthesis of nucleic acids; meanwhile fatty acids are used both as energetic
      substrates and as raw materials for lipid membranes. Furthermore, bio-energetic
      pathways are connected to pro-oncogenic signaling within glioma cells. For
      example: AMPK signaling links catabolism with cell cycle progression; mTOR
      signaling contributes to metabolic flexibility and cancer cell survival; the
      electron transport chain produces ATP and reactive oxygen species (ROS) which act
      as signaling molecules; Hypoxia Inducible Factors (HIFs) mediate interactions
      with cells and vasculature within the tumor environment. Mutations in the tumor
      suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase
      1 and 2 have been implicated in oncogenic signaling as well as establishing
      metabolic phenotypes in genetically-defined subsets of malignant glioma. These
      pathways critically contribute to tumor biology. The aim of this review is two
      fold. Firstly, we present the current state of knowledge regarding the metabolic
      strategies employed by malignant glioma cells, including aerobic glycolysis; the
      pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle,
      which is central to amino acid metabolism; oxidative phosphorylation; and fatty
      acid metabolism, which significantly contributes to energy production in glioma
      cells. Secondly, we highlight processes (including the Randle Effect, AMPK
      signaling, mTOR activation, etc.) which are understood to link bio-energetic
      pathways with oncogenic signals, thereby allowing the glioma cell to achieve a
      pro-malignant state.

PMID- 28491870
TI  - Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards
      Bedside.
AB  - The retinal vascular system is the only part of the human body available for
      direct, in vivo inspection. Noninvasive retinal markers are important to identity
      patients in risk of sight-threatening diabetic retinopathy. Studies have
      correlated structural features like retinal vascular caliber and fractals with
      micro- and macrovascular dysfunction in diabetes. Likewise, the retinal
      metabolism can be evaluated by retinal oximetry, and higher retinal venular
      oxygen saturation has been demonstrated in patients with diabetic retinopathy. So
      far, most studies have been cross-sectional, but these can only disclose
      associations and are not able to separate cause from effect or to establish the
      predictive value of retinal vascular dysfunction with respect to long-term
      complications. Likewise, retinal markers have not been investigated as markers of
      treatment outcome in patients with proliferative diabetic retinopathy and
      diabetic macular edema. The Department of Ophthalmology at Odense University
      Hospital, Denmark, has a strong tradition of studying the retinal
      microvasculature in diabetic retinopathy. In the present paper, we demonstrate
      the importance of the retinal vasculature not only as predictors of long-term
      microvasculopathy but also as markers of treatment outcome in sight-threatening
      diabetic retinopathy in well-established population-based cohorts of patients
      with diabetes.

PMID- 28491871
TI  - The Imbalance of B-Lymphocyte Subsets in Subjects with Different Glucose
      Tolerance: Relationship with Metabolic Parameter and Disease Status.
AB  - B lymphocytes are involved in inflammation and are related to insulin resistance
      in obesity and type 2 diabetes (T2D). This study investigated the phenotype and
      frequency of B-lymphocyte subsets in subjects recently diagnosed with T2D (n =
      60), impaired glucose regulation (IGR, n = 73), and normal glucose tolerance
      (NGT, n = 169) by flow cytometry. T2D subjects had an increased percentage of
      CD19+CD23+ (B-2) cells and a decreased percentage of CD19+CD23- (B-1) cells
      attributing to CD19+CD23-CD5- (B-1b) cells, but not CD19+CD23-CD5+ (B-1a) cells,
      compared to NGT and IGR subjects. The proportion of CD19+CD5+CD1dhi (B10) cells
      did not differ between the IGR or T2D group and NGT controls. Of note, HbA1c and
      triglyceride showed a positive correlation with B-2 cells but an inverse
      correlation with B-1 and B-1b cells, which were independently associated with the
      presence of T2D by logistic regression models. In summary, this study shows an
      unbalanced proinflammatory phenotype of B-cell subsets correlated with glycemia
      and lipidemia in patients with T2D. Our data provide new insight into chronic
      activation of the immune system and subclinical inflammation in T2D. Further
      prospective studies are warranted to confirm our observations.

PMID- 28491872
TI  - Incidence and Contributing Factors of Persistent Hyperglycemia at 6-12 Weeks
      Postpartum in Iranian Women with Gestational Diabetes: Results from LAGA Cohort
      Study.
AB  - Background. A history of gestational diabetes is an important predictor of many
      metabolic disturbances later in life. Method. Life after gestational diabetes
      Ahvaz Study (LAGAs) is an ongoing population-based cohort study. Up to February
      2016, 176 women with gestational diabetes underwent a 75 g oral glucose tolerance
      test (OGTT) at 6-12 weeks postpartum in Ahvaz (southwestern of Iran). Gestational
      diabetes was diagnosed according to the International Association of Diabetes and
      Pregnancy Study Groups (IADPSG) criteria and the American Diabetes Association
      (ADA) criteria applied for diagnosis of postpartum prediabetes and diabetes.
      Univariate and multivariate regression analysis were done. Results. Overall
      incidence of early postpartum glucose intolerance was 22.2% (95% CI, 16.3-29.0),
      17.6% prediabetes (95% CI, 12.3-24.1) and 4.5% diabetes (95% CI, 2.0-8.8%).
      Independent risk factors for glucose intolerance were FPG >= 100 at the time of
      OGTT (OR 3.86; 95% CI; 1.60-9.32), earlier diagnosis of GDM (OR 0.92; 95% CI;
      0.88-0.97), systolic blood pressure (OR 1.02; 95% CI; 1.002-1.04), and insulin or
      metformin therapy (OR 3.14; 95% CI; 1.20-8.21). Conclusion. Results determined a
      relatively high rate of glucose intolerance at 6-12 weeks after GDM pregnancy.
      Early postpartum screening of type 2 diabetes is needed particularly in women at
      high risk of type 2 diabetes.

PMID- 28491874
TI  - Innate-Adaptive Immune Crosstalk 2016.

PMID- 28491873
TI  - B-CD8+ T Cell Interactions in the Anti-Idiotypic Response against a Self
      Antibody.
AB  - P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and
      other self-antigens. This antibody is able to induce an anti-idiotypic IgG
      response and B-T idiotypic cascade, even in the absence of any adjuvant or
      carrier protein. P3 mAb immunization induces the expression of activation markers
      in a significant percentage of B-1a cells in vivo. Interestingly, transfer of
      both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response
      in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion
      of IFN-gamma and IL-4, although this activation was not detected ex vivo.
      Interestingly, naive CD8+ T cells increased the expression of activation markers
      and IFN-gamma secretion in the presence of B-1a cells isolated from P3 mAb
      immunized mice, even without in vitro restimulation. In contrast, B-2 cells were
      able to stimulate CD8+ T cells only if P3 was added in vitro. Using
      bioinformatics, a MHC class I-binding peptide from P3 VH region was identified.
      P3 mAb was able to induce a specific CTL response in vivo against cells
      presenting this peptide. Both humoral and CTL anti-idiotypic responses could be
      mechanisms to protect against the self-reactive antibody, contributing to keeping
      the tolerance to self-antigens.

PMID- 28491875
TI  - Understanding the Role of Chemokines and Cytokines in Experimental Models of
      Herpes Simplex Keratitis.
AB  - Herpes simplex keratitis is a disease of the cornea caused by HSV-1. It is a
      leading cause of corneal blindness in the world. Underlying molecular mechanism
      is still unknown, but experimental models have helped give a better understanding
      of the underlying molecular pathology. Cytokines and chemokines are small
      proteins released by cells that play an important proinflammatory or anti
      inflammatory role in modulating the disease process. Cytokines such as IL-17, IL
      6, IL-1alpha, and IFN-gamma and chemokines such as MIP-2, MCP-1, MIP-1alpha, and
      MIP-1beta have proinflammatory role in the destruction caused by HSV including
      neutrophil infiltration and corneal inflammation, and other chemokines and
      cytokines such as IL-10 and CCL3 can have a protective role. Most of the damage
      results from neutrophil infiltration and neovascularization. While many more
      studies are needed to better understand the role of these molecules in both
      experimental models and human corneas, current studies indicate that these
      molecules hold potential to be targets of future therapy.

PMID- 28491876
TI  - New Biomarkers in Autoimmune Disease.

PMID- 28491877
TI  - Nodular Regenerative Hyperplasia: A Case of Rare Prognosis.
AB  - Introduction: Nodular regenerative hyperplasia (NRH) is a known etiology of
      noncirrhotic portal hypertension. Cases of biopsy-proven NRH in human
      immunodeficiency virus (HIV)-positive patients have been described. While these
      patients often have normal synthetic liver function, several reports described
      disease progression to liver failure. Case: We here present a 26-year-old woman
      with history of congenital HIV on antiretroviral therapy complicated by
      Pneumocystis carinii pneumonia at age 14. CD4 counts have been >300 with
      undetectable viral load. She was referred to our Hepatology service for
      evaluation of splenomegaly, elevated liver tests, and thrombocytopenia. On
      initial presentation, she reported easy bruising and gingival bleeding, and
      abdominal imaging showed evidence of portal hypertension without associated
      cirrhosis. Upper endoscopy was significant for large esophageal varices without
      bleeding stigmata. Liver biopsy showed minimal fibrosis around the portal areas
      without significant inflammation. The lobules showed focal zones of thin
      hepatocyte plates on reticulin stain with adjacent areas showing mild
      regenerative changes. The diagnosis of NRH was made and patient was placed on
      propranolol for variceal bleeding prophylaxis. Two years later, the patient
      presented with bleeding gastric varices warranting transjugular intrahepatic
      portosystemic shunt. Postprocedure course was complicated by mild encephalopathy.
      Subsequent magnetic resonance imaging showed a 1.7 * 1.3 cm lesion suggestive of
      hepatocellular carcinoma (HCC). The patient was deemed to be a candidate for
      liver transplantation, and she is now delisted due to ongoing pregnancy.
      Conclusion: This report describes the first case of HCC in an HIV patient with
      NRH. The possible association of NRH with HCC warrants further investigation.

PMID- 28491878
TI  - A Case of Severe Neutropenia From Short-Term Exposure to Moxifloxacin.
AB  - Moxifloxacin is commonly prescribed in the inpatient and outpatient management of
      community-acquired pneumonia and other common infections. We report a case of a
      76-year-old man who developed severe neutropenia after several days of treatment
      for community-acquired pneumonia. The patient had a history of alcohol abuse;
      however, there were no other offending medications prescribed, and a thorough
      laboratory workup for other possible causes of neutropenia was negative. The
      patient's neutrophils and white blood count responded quickly to cessation of
      fluoroquinolones. This case highlights the importance of identifying patients
      that might be at high risk for neutropenia that may need closer monitoring on
      this commonly prescribed medication.

PMID- 28491879
TI  - Listeria Endocarditis: A Diagnostic Challenge.
AB  - A 74-year-old hemodialysis patient with a history of an atrial septum defect
      closure, coronary bypass surgery, and a St. Jude aortic prosthetic valve was
      diagnosed with pneumonia and volume overload. Blood cultures were positive for
      Listeria monocytogenes, and amoxicillin was given for 2 weeks. Immediately after
      discontinuation of amoxicillin, fever relapsed. Transthoracic and transesophageal
      echocardiography showed no sign of endocarditis. Given the fever relapse and 3
      positive minor Duke criteria, an 18F-FDG PET-CT scan (18F-fluorodeoxyglucose
      positron emission tomography-computed tomography) scan was performed. This scan
      showed activity at the aortic root, proximal ascending aorta, and inferior wall
      of the heart, making Listeria monocytogenes endocarditis a likely explanation.
      Amoxicillin was given for 6 weeks with good clinical result. Diagnosing a life
      threatening Listeria monocytogenes endocarditis can be challenging and an 18F-FDG
      PET-CT scan can be helpful.

PMID- 28491880
TI  - Iron Refractory Iron Deficiency Anemia in Dizygotic Twins Due to a Novel TMPRSS6
      Gene Mutation in Addition to Polymorphisms Associated With High Susceptibility to
      Develop Ferropenic Anemia.
AB  - Iron refractory iron deficiency anemia (IRIDA) is an autosomal recessive
      ferropenic anemia. Its hypochromic microcytic pattern is associated with low
      transferrin saturation, normal-high ferritin, and inappropriately high hepcidin
      level. This entity is caused by mutants of the TMPRSS6 gene that encodes the
      protein matriptase II, which influences hepcidin expression, an iron metabolism
      counterregulatory protein. We report two 29-year-old dizygotic female twins with
      ferropenic, hypochromic microcytic anemia with 20 years of evolution, refractory
      to oral iron therapy. After exclusion of gastrointestinal etiologies, IRIDA
      diagnosis was suspected and a novel mutation in the TMPRSS6 gene was identified.
      It was found in intron 11 (c.1396+4 A>T) and seems to affect the gene expression.
      In addition, 3 polymorphisms already associated with a higher risk of developing
      iron deficiency anemia were also found (D521D, V736A, and Y739Y). Our case
      reports an undescribed mutation causing IRIDA and supports the hypothesis that
      this clinical syndrome may be more common than previously thought and its
      genetics more heterogeneous than initially described.

PMID- 28491881
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2324709616689106.].

PMID- 28491882
TI  - Portal Vein Thrombosis in the Setting of Newly Diagnosed Cushing's Syndrome.
AB  - The hallmark manifestations of Cushing's syndrome (CS) are well known, but
      hypercoagulability is perhaps least recognized. Patients with CS are at increased
      risk of both spontaneous and postoperative thromboembolism, with the significant
      majority of events occurring in the lower extremity and pulmonary venous
      circulations. We present a case of portal vein thrombosis (PVT) occurring in the
      setting of newly diagnosed CS due to a left adrenal adenoma. Factor VIII activity
      was approximately 2.5-fold elevated, a known mechanism by which hypercortisolemia
      predisposes to venous thrombosis. Acute abdominal pain and fever responded well
      to unfractionated heparin and parenteral antibiotics, and CS was eventually cured
      by left adrenalectomy. No thromboembolic events have occurred since surgery. PVT
      is uncommon and usually occurs as a complication of primary or secondary
      hepatobiliary malignancies and cirrhosis. To the best of our knowledge, this is
      just the second reported case of PVT due to CS and the first published in the
      English language literature.

PMID- 28491883
TI  - Haemophilus parainfluenzae Endocarditis Associated With Maxillary Sinusitis and
      Complicated by Cerebral Emboli in a Young Man.
AB  - HACEK endocarditis is often difficult to diagnose given the slow-growing
      characteristics of the organisms involved. Haemophilus parainfluenzae, one of the
      HACEK organisms, is an uncommon cause of endocarditis. We describe a case of a
      previously healthy young man with H parainfluenzae endocarditis that was
      associated with maxillary sinusitis and severe systemic complications, including
      septic cerebral emboli and mitral valve perforation. Previously reported cases
      have also described a predilection for younger people, cardiac valve pathology,
      and a high prevalence of stroke.

PMID- 28491884
TI  - Association of Autoimmune Hepatitis and Celiac Disease: Role of Gluten-Free Diet
      in Reversing Liver Dysfunction.
AB  - Autoimmune hepatitis (AIH) is a chronic inflammation of liver with unclear
      etiology. It is frequently associated other autoimmune diseases, and its
      association with celiac disease (CD) is well established. In this article, we
      describe the case of a 50-year-old male with long-standing AIH taking
      azathioprine for 10 years, evaluated for flares in transaminases. Despite adding
      high-dose corticosteroids, his transaminases and bilirubin remained high.
      Serology for CD was ordered, which revealed elevated tissue transglutaminase
      antibody IgG and endomysial IgA, which was further confirmed by endoscopic
      biopsy. Strict gluten-free diet was advised and now for over 2 years he is in
      remission with azathioprine and budesonide. This emphasizes the role of gluten
      free diet in reversing liver dysfunction in patients with AIH, and clinicians
      should consider screening for CD in patients with AIH with persistent elevation
      of liver enzymes despite immunosuppressant treatment.

PMID- 28491886
TI  - The Effect of the Number of Carries Among College Running Backs on Future Injury
      Risk and Performance in the National Football League.
AB  - BACKGROUND: There has been speculation that running backs with an excessive
      number of carries in college are less likely to be successful in the National
      Football League (NFL). PURPOSE: To determine whether there is a correlation
      between number of carries by college running backs and future performance and
      injury risk in the NFL. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: Using the ESPN archives of National Collegiate Athletic Association and
      NFL running backs, the following inclusion criteria were used: running backs who
      played their last college season from 1999 through 2012 and who were drafted in
      the first 4 rounds of the NFL draft following their college career. Players were
      grouped by number of carries during their final college season (group A, 100-200
      carries; group B, 250+ carries). Performance and injury risk were compared
      between groups during the first 3 eligible seasons in the NFL. Groups were
      compared based on total number of carries, mean yards per carry, number of games
      missed due to injury, and the specific injuries resulting in missed playing time.
      RESULTS: During the seasons studied, a total of 103 running backs were included
      (group A, n = 42; group B, n = 61). There was a trend toward a significantly
      greater mean total number of carries through 3 NFL seasons in group B (group A, n
      = 276 carries; group B, n = 376 carries; P = .058). Mean yards per carry did not
      differ between groups (group A, n = 3.9 yards/carry; group B, n = 4.0
      yards/carry; P = .67). Groups A and B missed a mean 5.8 and 5.7 games,
      respectively, due to injury during their first 3 NFL seasons (P = .98). A
      significantly greater proportion of players in group A suffered a concussion
      compared with group B (P = .014). CONCLUSION: There is no correlation between the
      number of carries by college running backs and future injury risk or performance
      during their early NFL career.

PMID- 28491885
TI  - Effects of Sex and Event Type on Head Impact in Collegiate Soccer.
AB  - BACKGROUND: The effects of head impact in sports are of growing interest for
      clinicians, scientists, and athletes. Soccer is the most popular sport worldwide,
      but the burden of head impact in collegiate soccer is still unknown. PURPOSE: To
      quantify head impact associated with practicing and playing collegiate soccer
      using wearable accelerometers. STUDY DESIGN: Descriptive epidemiological study.
      METHODS: Mastoid patch accelerometers were used to quantify head impact in
      soccer, examining differences in head impact as a function of sex and event type
      (practice vs game). Seven female and 14 male collegiate soccer players wore
      mastoid patch accelerometers that measured head impacts during team events. Data
      were summarized for each athletic exposure, and statistical analyses evaluated
      the mean number of impacts, mean peak linear acceleration, mean peak rotational
      acceleration, and cumulative linear and rotational acceleration, each grouped by
      sex and event type. RESULTS: There were no differences in the frequency or
      severity of head impacts between men's and women's soccer practices. For men's
      soccer, games resulted in 285% more head impacts than practices, but there were
      no event-type differences in mean impact severity. Men's soccer games resulted in
      more head impacts than practices across nearly all measured impact severities,
      which also resulted in men's soccer games producing a greater cumulative impact
      burden. CONCLUSION: Similar to other sports, men's soccer games have a greater
      impact burden when compared with practices, and this effect is driven by the
      quantity rather than severity of head impacts. In contrast, there were no
      differences in the quantity or severity of head impacts in men's and women's
      soccer practices. These data could prompt discussions of practical concern to
      collegiate soccer, such as understanding sex differences in head impact and
      whether games disproportionately contribute to an athlete's head impact burden.

PMID- 28491887
TI  - Risk Factors for Surgical Site Infection After Cholecystectomy.
AB  - BACKGROUND: There are limited data on risk factors for surgical site infection
      (SSI) after open or laparoscopic cholecystectomy. METHODS: A retrospective cohort
      of commercially insured persons aged 18-64 years was assembled using
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9-CM) procedure or Current Procedural Terminology, 4th edition codes for
      cholecystectomy from December 31, 2004 to December 31, 2010. Complex procedures
      and patients (eg, cancer, end-stage renal disease) and procedures with pre
      existing infection were excluded. Surgical site infections within 90 days after
      cholecystectomy were identified by ICD-9-CM diagnosis codes. A Cox proportional
      hazards model was used to identify independent risk factors for SSI. RESULTS:
      Surgical site infections were identified after 472 of 66566 (0.71%)
      cholecystectomies; incidence was higher after open (n = 51, 4.93%) versus
      laparoscopic procedures (n = 421, 0.64%; P < .001). Independent risk factors for
      SSI included male gender, preoperative chronic anemia, diabetes, drug abuse,
      malnutrition/weight loss, obesity, smoking-related diseases, previous
      Staphylococcus aureus infection, laparoscopic approach with acute
      cholecystitis/obstruction (hazards ratio [HR], 1.58; 95% confidence interval
      [CI], 1.27-1.96), open approach with (HR, 4.29; 95% CI, 2.45-7.52) or without
      acute cholecystitis/obstruction (HR, 4.04; 95% CI, 1.96-8.34), conversion to open
      approach with (HR, 4.71; 95% CI, 2.74-8.10) or without acute
      cholecystitis/obstruction (HR, 7.11; 95% CI, 3.87-13.08), bile duct exploration,
      postoperative chronic anemia, and postoperative pneumonia or urinary tract
      infection. CONCLUSIONS: Acute cholecystitis or obstruction was associated with
      significantly increased risk of SSI with laparoscopic but not open
      cholecystectomy. The risk of SSI was similar for planned open and converted
      procedures. These findings suggest that stratification by operative factors is
      important when comparing SSI rates between facilities.

PMID- 28491888
TI  - Successful Treatment of Allergic Bronchopulmonary Aspergillosis With
      Isavuconazole: Case Report and Review of the Literature.
AB  - Isavuconazole is a new triazole that is approved for primary therapy of invasive
      aspergillosis. We provide the first report of a patient with allergic
      bronchopulmonary aspergillosis (ABPA) who was successfully treated with
      isavuconazole with marked improvement and minimal adverse effects. We further
      review the literature on antifungal management of ABPA.

PMID- 28491890
TI  - Dengue Virus Entry and Replication Does Not Lead to Productive Infection in
      Platelets.
AB  - Thrombocytopenia is a characteristic feature during the acute phase of dengue
      infection and has been found to associate with vascular leakage in severe dengue.
      Although dengue antigens have been observed in platelets, there is no strong
      evidence to suggest a direct infection of platelets by dengue virus as a
      contributing factor for thrombocytopenia. We show that dengue virus can enter
      platelets but replicate viral ribonucleic acid to a minimal extent and,
      therefore, cannot produce infectious virus. Dengue antigen was undetectable in
      platelets isolated from dengue patients; however, we observed an increase in
      CD14+CD16+ monocyte-platelet complexes, suggesting a mechanism for platelet
      clearance.

PMID- 28491889
TI  - Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ
      Transplant Infection Project, a Multicenter, Prospective, Cohort Study.
AB  - BACKGROUND: Infection is a major cause of morbidity and mortality after
      allogeneic hematopoietic cell transplantation (HCT). Our object was to better
      define the epidemiology and outcomes of infections after HCT. METHODS: This was a
      prospective, multicenter cohort study of HCT recipients and conducted from 2006
      to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data
      were prospectively collected for up to 30 months after HCT using a standardized
      data collection tool. RESULTS: The median age was 53 years, and median follow up
      was 413 (range, 5-980) days. The most common reason for HCT was hematologic
      malignancy (87%). The overall crude mortality was 52%. Death was due to
      underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231
      (52%) cases and occurred early posttransplant (median day 48). Gram-negative
      bloodstream infections were less frequent than Gram-positive, but it was
      associated with higher mortality (45% vs 13%, P = .02). Clostridium difficile
      infection developed in 148 patients (33%) at a median of 27 days post-HCT. There
      were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median
      time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection,
      4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13
      (4%) cases and was disseminated in 2. Infection with respiratory viruses was seen
      in 49 patients. Pneumocystis jirovecii pneumonia was rare (1%), and there were no
      documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial
      infection. This study lacked standardized antifungal and antiviral prophylactic
      strategies. CONCLUSIONS: Infection remains a significant cause of morbidity and
      mortality after HCT. Bacteremias and C difficile infection are frequent,
      particularly in the early posttransplant period. The rate of IFI is approximately
      10%. Organ involvement with CMV is infrequent, as are serious infections with VZV
      and herpes simplex virus, likely reflecting improved prevention strategies.

PMID- 28491891
TI  - A Report of Adult Human Adenovirus Infections in a Tertiary Hospital.
AB  - We describe a review of human adenovirus (HAdV) infections occurring among adults
      in a tertiary hospital in Singapore from February to May 2013. A similar increase
      in cases was observed among children and military personnel during the same time
      period. The majority of isolates were identified as HAdV-7, likely an emerging
      pathogen in Asia.

PMID- 28491892
TI  - Evaluation of a Novel Alcohol-Based Surface Disinfectant for Disinfection of Hard
      and Soft Surfaces in Healthcare Facilities.
AB  - We examined the efficacy of a new 1-step cleaner and disinfectant containing 30%
      ethanol that is applied as a spray. The product rapidly reduced vegetative
      bacterial pathogens on carriers and on hard and soft surfaces in healthcare
      settings, but it did not stain clothing.

PMID- 28491893
TI  - Predictors of Dengue-Related Mortality and Disease Severity in a Tertiary Care
      Center in North India.
AB  - BACKGROUND: There is lack of reliable predictors of disease severity and
      mortality in dengue. The present study was carried out to identify these
      predictors during the 2015 outbreak in India. METHODS: This prospective
      observational study included confirmed adult dengue patients hospitalized between
      August and November 2015 in a tertiary care centre in New Delhi, India.
      Appropriate statistical tests were used to compare clinicolaboratory
      characteristics, derive predictors of severe disease and mortality, and compute a
      predictive score for mortality. Serotyping was done. RESULTS: Data of 369
      patients were analyzed (mean age, 30.9 years; 67% males). Of these, 198 (54%)
      patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (grade 1 or 2),
      and 46 (12%) developed dengue shock syndrome (DSS). Twenty-two (6%) patients
      died. Late presentation to the hospital (>=5 days after onset) and dyspnea at
      rest were identified as independent predictors of severe disease. Age >=24 years,
      dyspnea at rest and altered sensorium were identified as independent predictors
      of mortality. A clinical risk score was developed (12*age + 14*sensorium +
      10*dyspnea), which, if >=22, predicted mortality with a high sensitivity (81.8%)
      and specificity (79.2%). The predominant serotypes in Delhi (2015) were dengue
      virus DENV2 and DENV4. CONCLUSION: Age >=24 years, dyspnea at rest, and altered
      sensorium were identified as independent predictors of mortality. Platelet counts
      did not determine outcome in dengue patients. Timely referral/access to
      healthcare is important. The clinical risk score for mortality prediction that
      was developed in this study can be used in all healthcare settings, after
      validation in larger cohorts.

PMID- 28491894
TI  - Curative Effects for B-Cell Lymphoma Accomplished by Direct-Acting Antiviral
      Agents of Hepatitis C.
AB  - Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus with the
      capabilities of tumorigenesis. We present an HCV-infected patient affected with B
      cell lymphomas after suffering from hepatocellular carcinoma. The patient
      exhibited curative effects for lymphomas after treatment with sofosbuvir and
      ledipasvir, which is shown clearly with a positron emission tomography scanner.

PMID- 28491895
TI  - Pyogenic Arthritis of the Fingers and the Wrist: Can We Shorten Antimicrobial
      Treatment Duration?
AB  - BACKGROUND: Pyogenic arthritis of the small joints of the hand and wrist is a
      known but poorly described entity. The objective of this work was to characterize
      the clinical presentation, antimicrobial treatment, and surgical interventions of
      native small joint arthritis (SJA) treated in our tertiary center. METHODS:
      According to predefined variables, medical records of adult patients with SJA
      treated in a Swiss university hospital between 2005 and 2013 were retrospectively
      analyzed. RESULTS: The median age of 97 patients (101 joints) was 52 years
      (interquartile range [IQR], 38-68 years); 52% had no comorbidity. Small joint
      arthritis of the second and third fingers accounted for 53% of infections, with
      metacarpal-phalangeal and proximal interphalangeal joints most commonly involved.
      Of 86 (89%) episodes with an exogenous source, 63 (65%) followed a trauma. The
      most commonly isolated microorganism was Staphylococcus aureus (38%), followed by
      beta-hemolytic streptococci (13%) and Pasteurella spp (11%). Eighty-seven
      episodes (89 joints) in patients with follow-up examinations were included in
      treatment and outcome analyses. Up to 2 surgical interventions were required to
      cure infection in 74 (83%) joints. Median antimicrobial treatment duration was 14
      days (IQR, 12-28 days), with amoxicillin/clavulanate administered in 74 (85%)
      episodes. At follow up, cure of infection was noted in all episodes and good
      functional outcome in 79% of episodes. CONCLUSIONS: Small joint arthritis shows
      considerable differences from clinical patterns reported for larger joints. In
      our series, the outcome was good with no more than 2 surgical interventions and
      median treatment duration of 14 days in 79% of episodes.

PMID- 28491896
TI  - Physical activity predicts reduced plasma beta amyloid in the Cardiovascular
      Health Study.
AB  - OBJECTIVE: Higher levels of physical activity (PA) reduce the risk of cognitive
      impairment, but the underlying mechanisms are unclear. Using longitudinal data
      from the Cardiovascular Health Study, we examined whether PA predicted plasma
      Abeta levels and risk for cognitive decline 9-13 years later. METHODS: Linear and
      logistic regressions (controlling for APOE status, age, gender, body mass index,
      cardiovascular disease, brain white matter lesions, and cystatin C levels) tested
      associations between PA, Abeta, and cognitive impairment in a sample of 149
      cognitively normal older adults (mean age 83 years). RESULTS: More PA at baseline
      predicted lower levels of Abeta 9-13 years later. Higher Abeta levels at year 9
      predicted greater risk for cognitive impairment at year 13. Levels of Abeta at
      year 9 mediated the relationship between PA and cognitive impairment.
      INTERPRETATION: Greater PA may reduce plasma levels of a neurotoxic peptide at an
      age when the risk for cognitive impairment is especially high.

PMID- 28491897
TI  - Longitudinal characterization of biomarkers for spinal muscular atrophy.
AB  - OBJECTIVE: Recent advances in understanding Spinal Muscular Atrophy (SMA)
      etiopathogenesis prompted development of potent intervention strategies and
      raised need for sensitive outcome measures capable of assessing disease
      progression and response to treatment. Several biomarkers have been proposed;
      nevertheless, no general consensus has been reached on the most feasible ones. We
      observed a wide range of measures over 1 year to assess their ability to monitor
      the disease status and progression. METHODS: 18 SMA patients and 19 healthy
      volunteers (HV) were followed in this 52-weeks observational study. Quantitative
      MRI (qMRI) of both thighs and clinical evaluation of motor function was performed
      at baseline, 6, 9 and 12 months follow-up. Blood samples were taken in patients
      for molecular characterization at screening, 9 and 12 month follow-up.
      Progression, responsiveness and reliability of collected indices were quantified.
      Correlation analysis was performed to test for potential associations. RESULTS:
      QMRI indices, clinical scales and molecular measures showed high to excellent
      reliability. Significant differences were found between qMRI of SMA patients and
      HV. Significant associations were revealed between multiple qMRI measures and
      functional clinical scales. None of the qMRI, clinical, or molecular measures was
      able to detect significant disease progression over 1 year. INTERPRETATION: We
      probed a variety of quantitative measures for SMA in a slowly-progressing disease
      population over 1 year. The presented measures demonstrated potential to provide
      a closer link to underlying disease biology as compared to conventional
      functional scales. The proposed biomarker framework can guide implementation of
      more sensitive endpoints in future clinical trials and prove their utility in
      search for novel disease-modifying therapies.

PMID- 28491898
TI  - A Cross-sectional population-based investigation into behavioral change in
      amyotrophic lateral sclerosis: subphenotypes, staging, cognitive predictors, and
      survival.
AB  - OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is a clinically heterogeneous
      neurodegenerative disorder associated with cognitive and behavioral impairment.
      The primary aim of this study was to identify behavioral subphenotypes in ALS
      using a custom designed behavioral assessment tool (Beaumont Behavioural
      Inventory, BBI). Secondary aims were to (1) investigate the predictive nature of
      cognitive assessment on behavioral change, (2) report the behavioral profile
      associated with the C9orf72 expansion, (3) categorize behavioral change through
      disease staging, and (4) to investigate the relationship between cross-sectional
      behavioral classification and survival. METHODS: A cross-sectional population
      based research design was applied to examine behavioral data from ALS patients (n
      = 317) and healthy controls (n = 66). Patients were screened for the C9orf72
      repeat expansion. A subcohort of ALS patients completed an extensive cognitive
      assessment battery (n = 65), to investigate predictors of behavior change.
      Principal component analysis (PCA) determined factors associated with altered
      behavior. Survival data were extracted from the Irish ALS register. RESULTS: No
      behavioral changes were reported in 180 patients (57%); 95 patients had mild
      moderate behavioral change (30%); 42 patients met the cut-off for Clinically
      Severe Behavioral Change (13%), suggestive of a bvFTD diagnosis. The most
      frequently endorsed behaviors in ALS were reduced concern for hygiene (36.8%),
      irritability (36.2%), new unusual habits (33.4%), and increased apathy (31.1%).
      Five independent factors were identified through factor analysis. Social
      cognitive performance was predictive of behavior change (P = 0.031), yielding an
      R2 = 0.188. Behavioral categorization (mild/moderate/severe) at the time of
      assessment was not associated with survival (P = 0.198). INTERPRETATION: These
      data imply the presence of distinct subphenotypes of behavioral change in ALS,
      which most likely reflect subcategories of extramotor network disruption.

PMID- 28491900
TI  - Screening of conventional anticonvulsants in a genetic mouse model of epilepsy.
AB  - OBJECTIVE: Epilepsy is a common neurological disorder that affects 1% of the
      population. Approximately, 30% of individuals with epilepsy are refractory to
      treatment, highlighting the need for novel therapies. Conventional anticonvulsant
      screening relies predominantly on induced seizure models. However, these models
      may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are
      a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet
      syndrome typically begins in infancy with seizures provoked by fever and then
      progresses to include afebrile pleomorphic seizure types. Affected children
      respond poorly to available anticonvulsants. Scn1a+/- heterozygous knockout mice
      recapitulate features of Dravet syndrome and provide a potential screening
      platform to investigate novel therapeutics. In this study, we conducted a
      screening of conventional anticonvulsants in Scn1a+/- mice to establish assays
      that most closely correlate with human response data. METHODS: On the basis of
      clinical response data from a large, single center, retrospective survey of
      Dravet syndrome case records, we selected nine drugs for screening in Scn1a+/-
      mice to determine which phenotypic measures correlate best with human therapeutic
      response. We evaluated several screening paradigms and incorporated
      pharmacokinetic monitoring to establish drug exposure levels. RESULTS: Scn1a+/-
      mice exhibited responses to anticonvulsant treatment similar to those observed
      clinically. Sodium channel blockers were not effective or exacerbated seizures in
      Scn1a+/- mice. Overall, clobazam was the most effective anticonvulsant in Scn1a+/
      mice, consistent with its effect in Dravet syndrome. INTERPRETATION: Genetic
      models of spontaneous epilepsy provide alternative screening platforms and may
      augment the AED development process. In this study, we established an effective
      screening platform that pharmacologically validated Scn1a+/- mice for preclinical
      screening of potential Dravet syndrome therapeutics.

PMID- 28491899
TI  - Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.
AB  - OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole
      exome sequencing (WES) in a cohort of individuals with peripheral neuropathy.
      METHODS: Singleton WES was performed in individuals recruited though one
      pediatric and one adult tertiary center between February 2014 and December 2015.
      Initial analysis was restricted to a virtual panel of 55 genes associated with
      peripheral neuropathies. Patients with uninformative results underwent expanded
      analysis of the WES data. Data on the cost of prior investigations and
      assessments performed for diagnostic purposes in each patient was collected.
      RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age
      18 years; range 2-68 years). The median time from initial presentation to study
      enrollment was 6 years 9 months (range 2 months-62 years), and the average cost
      of prior investigations and assessments for diagnostic purposes AU$4013 per
      patient. Eleven individuals received a diagnosis from the virtual panel. Eight
      individuals received a diagnosis following expanded analysis of the WES data,
      increasing the overall diagnostic yield to 38%. Two additional individuals were
      diagnosed with pathogenic copy number variants through SNP microarray.
      CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility
      and is cost effective in patients with a peripheral neuropathy. Expanded analysis
      of WES data significantly improves the diagnostic yield in patients in whom a
      diagnosis is not found on the initial targeted analysis. This is primarily due to
      diagnosis of conditions caused by newly discovered genes and the resolution of
      complex and atypical phenotypes.

PMID- 28491901
TI  - Predictors of clinical recovery from vestibular neuritis: a prospective study.
AB  - We sought to identify predictors of symptomatic recovery in vestibular neuritis.
      Forty VN patients were prospectively studied in the acute phase (median = 2 days)
      and 32 in the recovery phase (median = 10 weeks) with vestibulo-ocular reflex,
      vestibular-perceptual, and visual dependence tests and psychological
      questionnaires. Clinical outcome was Dizziness Handicap Inventory score at
      recovery phase. Acute visual dependency and autonomic arousal predicted outcome.
      Worse recovery was associated with a combination of increased visual dependence,
      autonomic arousal, anxiety/depression, and fear of bodily sensations, but not
      with vestibular variables. Findings highlight the importance of early
      identification of abnormal visual dependency and concurrent anxiety.

PMID- 28491902
TI  - De novo REEP2 missense mutation in pure hereditary spastic paraplegia.
AB  - Alterations in proteins that regulate endoplasmic reticulum morphology are common
      causes of hereditary spastic paraplegia (SPG1-78, plus others). Mutations in the
      REEP1 gene that encodes an endoplasmic reticulum-shaping protein are well-known
      causes of SPG31, a common autosomal dominant spastic paraplegia. A closely
      related gene, REEP2, is mutated in SPG72, with both autosomal and recessive
      inheritances. Here, we report a patient with a pure hereditary spastic paraplegia
      due to a de novo missense mutation (c.119T > G, p.Met40Arg) in REEP2 at a highly
      conserved residue very close to another known pathogenic missense change. This
      represents only the second autosomal dominant SPG72 missense mutation reported.

PMID- 28491904
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1002/acn3.387.].

PMID- 28491903
TI  - Dimethyl fumarate alters B-cell memory and cytokine production in MS patients.
AB  - We evaluated the effect of dimethyl fumarate (DMF) treatment on B-cell memory and
      cytokine production in 18 patients with relapsing remitting multiple sclerosis
      (RRMS) using peripheral blood mononuclear cells obtained prior to and at 6 months
      post-DMF initiation. We noted a decline in the absolute B-cell number with DMF
      treatment, with a preferential depletion of memory B cells and a concurrent
      increase in naive B cells. We noted significant reductions in GM-CSF, TNF-alpha,
      and IL-6 producing B cells with DMF treatment. These effects on the B-cell
      compartment may underlie the beneficial effects of DMF in RRMS.

PMID- 28491905
TI  - Genetically expressed voltage sensor ArcLight for imaging large scale cortical
      activity in the anesthetized and awake mouse.
AB  - With the recent breakthrough in genetically expressed voltage indicators (GEVIs),
      there has been a tremendous demand to determine the capabilities of these sensors
      in vivo. Novel voltage sensitive fluorescent proteins allow for direct
      measurement of neuron membrane potential changes through changes in fluorescence.
      Here, we utilized ArcLight, a recently developed GEVI, and examined the
      functional characteristics in the widely used mouse somatosensory whisker
      pathway. We measured the resulting evoked fluorescence using a wide-field
      microscope and a CCD camera at 200 Hz, which enabled voltage recordings over the
      entire cortical region with high temporal resolution. We found that ArcLight
      produced a fluorescent response in the S1 barrel cortex during sensory
      stimulation at single whisker resolution. During wide-field cortical imaging, we
      encountered substantial hemodynamic noise that required additional post hoc
      processing through noise subtraction techniques. Over a period of 28 days, we
      found clear and consistent ArcLight fluorescence responses to a simple sensory
      input. Finally, we demonstrated the use of ArcLight to resolve cortical S1
      sensory responses in the awake mouse. Taken together, our results demonstrate the
      feasibility of ArcLight as a measurement tool for mesoscopic, chronic imaging.

PMID- 28491906
TI  - Mammalian cortical voltage imaging using genetically encoded voltage indicators:
      a review honoring professor Amiram Grinvald.
AB  - The pioneering work of Amiram Grinvald established voltage-sensitive dye imaging
      (VSDI) in the mammalian cortex in the 1980s and inspired decades of cortical
      voltage imaging and the associated technological developments. The recent
      conception and development of genetically encoded voltage indicators (GEVIs)
      overcome many of the limitations of classical VSDI, and open experimental
      approaches that provide accruing support for orchestrated neuronal circuit
      dynamics of spatially distributed neuronal circuit underlying behaviors. We will
      review recent achievements using GEVIs to optically monitor the cortical activity
      in mammalian brains in vivo and provide a perspective for potential future
      directions.

PMID- 28491907
TI  - Comprehensive assessment of patient image quality and radiation dose in latest
      generation cardiac x-ray equipment for percutaneous coronary interventions.
AB  - This study aimed to determine whether a reduction in radiation dose was found for
      percutaneous coronary interventional (PCI) patients using a cardiac
      interventional x-ray system with state-of-the-art image enhancement and x-ray
      optimization, compared to the current generation x-ray system, and to determine
      the corresponding impact on clinical image quality. Patient procedure dose area
      product (DAP) and fluoroscopy duration of 131 PCI patient cases from each x-ray
      system were compared using a Wilcoxon test on median values. Significant
      reductions in patient dose ([Formula: see text]) were found for the new system
      with no significant change in fluoroscopy duration ([Formula: see text]);
      procedure DAP reduced by 64%, fluoroscopy DAP by 51%, and "cine" acquisition DAP
      by 76%. The image quality of 15 patient angiograms from each x-ray system (30
      total) was scored by 75 clinical professionals on a continuous scale for the
      ability to determine the presence and severity of stenotic lesions; image quality
      scores were analyzed using a two-sample [Formula: see text]-test. Image quality
      was reduced by 9% ([Formula: see text]) for the new x-ray system. This
      demonstrates a substantial reduction in patient dose, from acquisition more than
      fluoroscopy imaging, with slightly reduced image quality, for the new x-ray
      system compared to the current generation system.

PMID- 28491908
TI  - Lack of agreement between radiologists: implications for image-based model
      observers.
AB  - We tested the agreement of radiologists' rankings of different reconstructions of
      breast computed tomography images based on their diagnostic (classification)
      performance and on their subjective image quality assessments. We used 102
      pathology proven cases (62 malignant, 40 benign), and an iterative image
      reconstruction (IIR) algorithm to obtain 24 reconstructions per case with
      different image appearances. Using image feature analysis, we selected 3 IIRs and
      1 clinical reconstruction and 50 lesions. The reconstructions produced a range of
      image quality from smooth/low-noise to sharp/high-noise, which had a range in
      classifier performance corresponding to AUCs of 0.62 to 0.96. Six experienced
      Mammography Quality Standards Act (MQSA) radiologists rated the likelihood of
      malignancy for each lesion. We conducted an additional reader study with the same
      radiologists and a subset of 30 lesions. Radiologists ranked each reconstruction
      according to their preference. There was disagreement among the six radiologists
      on which reconstruction produced images with the highest diagnostic content, but
      they preferred the midsharp/noise image appearance over the others. However, the
      reconstruction they preferred most did not match with their performance. Due to
      these disagreements, it may be difficult to develop a single image-based model
      observer that is representative of a population of radiologists for this
      particular imaging task.

PMID- 28491909
TI  - Fluorescent Detection of Intracellular Nitric Oxide in Staphylococcus aureus.
AB  - Nitric Oxide (NO) is a highly-reactive radical gas that can modify a variety of
      cellular targets in both eukaryotes and bacteria. NO is produced endogenously by
      a wide variety of organisms: For example, as a cell-signaling molecule in mammals
      and bacteria via nitric oxide synthase (NOS) enzymes, and as a product of
      denitrification. As such, it is of great benefit to NO researchers to be able to
      sensitively detect intracellular NO and stable reactive nitrogen species (RNS)
      derived from NO. To this end, a protocol for fluorescent detection of
      intracellular NO/RNS in biofilm cultures of the Gram-positive pathogen
      Staphylococcus aureus has been optimized using the commercially-available cell
      permeable fluorescent stain 4-Amino-5-Methylamino-2', 7'-Difluorofluorescein
      Diacetate (DAF-FM diacetate). This compound diffuses into cells and intracellular
      cleavage by esterase enzymes liberates weakly-fluorescent DAF-FM, which reacts
      with NO or other specific RNS to become highly fluorescent (Kojima et al., 1999).
      Although quantification of fluorescence is performed using a fluorescent plate
      reader, it is envisioned that this protocol could be adapted for intracellular
      NO/RNS imaging of S. aureus biofilms by confocal microscopy. Likewise, this
      technique could be optimized for the detection of intracellular NO/RNS in other
      growth conditions (i.e., planktonic cultures) and/or in other bacteria/archaea.

PMID- 28491910
TI  - Social Disadvantage Is Associated With Lower Vitamin D Levels in Older People and
      There Is No Surrogate for Its Measurement.
AB  - Introduction: There is increasing evidence concerning adverse health consequences
      of low vitamin D levels. We determined whether there is any surrogate for
      measuring vitamin D in people older than 70 years and the relation between index
      of multiple deprivation (IMD) and vitamin D levels. Methods: Blood samples from
      241 patients were included in this analysis. Concurrent measurements for 25
      hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and bone profile are
      reported. Results: The prevalence of total vitamin D insufficiency/deficiency
      (defined as total vitamin D <50 nmol/L) was 57.5% overall. Even for patients with
      vitamin D deficiency, a significant proportion had PTH, normal calcium,
      phosphate, and alkaline phosphatase levels. For patients with vitamin D <25
      nmol/L, 62.7% had a PTH within reference range, 83.1% had normal serum-adjusted
      calcium, 80.6% had normal phosphate, and 85.1% had a normal serum alkaline
      phosphatase. With increasing quintiles of IMD, there was a 22% increased risk of
      vitamin D deficiency/insufficiency from quintiles 1 to 5, in age- and sex
      adjusted logistic regression models (odds ratio [OR] = 1.22, 95% confidence
      interval [1.01, 1.47]; p = .034). Conclusion: No other parameter is currently
      adequate for screening for vitamin D deficiency in older people. A higher IMD is
      associated with lower vitamin D levels in older people.

PMID- 28491911
TI  - Navigating Long-Term Care.
AB  - Americans over age 65 constitute a larger percentage of the population each year:
      from 14% in 2010 (40 million elderly) to possibly 20% in 2030 (70 million
      elderly). In 2015, an estimated 66 million people provided care to the ill,
      disabled, and elderly in the United States. In 2000, according to the Centers for
      Disease Control and Prevention (CDC), 15 million Americans used some form of long
      term care: adult day care, home health, nursing home, or hospice. In all, 13% of
      people over 85 years old, compared with 1% of those ages 65 to 74, live in
      nursing homes in the United States. Transitions of care, among these various
      levels of care, are common: Nursing home to hospital transfer, one of the best
      studied transitions, occurs in more than 25% of nursing home residents per year.
      This article follows one patient through several levels of care.

PMID- 28491912
TI  - Association Between Home Visit Programs and Emergency Preparedness Among Elderly
      Vulnerable People in New South Wales, Australia.
AB  - Objective: The purpose of this study is to examine the association between home
      visit programs and emergency preparedness among elderly vulnerable people in New
      South Wales, Australia. Method: The study used data acquired from an intervention
      program run by emergency agencies and consisted of 370 older people. Seven
      emergency outcome measures were examined by adjusting for key demographic
      factors, using a generalized estimating equation model, to examine the
      association between home visit programs and emergency preparedness. Results: The
      study revealed that knowledge demonstrated by participants during visits and post
      home visits showed significant improvements in the seven emergency outcome
      measures. The odds of finding out what emergencies might affect one's area were
      significantly lower among older participants who were born outside Australia and
      those who were women. Discussion: The findings suggest that the intervention via
      home visits and periodic reminders post these visits may be a useful intervention
      in improving emergency preparedness among older people, especially among men and
      those who were born outside of Australia. In addition, other reminders such as
      safety messaging via mobile or landline telephone calls may also be a
      supplementary and useful intervention to improve emergency preparedness among
      older people.

PMID- 28491913
TI  - Teaching Our Doctors to Care for the Elderly: A Geriatrics Needs Assessment
      Targeting Internal Medicine Residents.

PMID- 28491914
TI  - Exploring the Housing Needs of Older People in Standard and Sheltered Social
      Housing.
AB  - Objective: Our home can have a major impact on our physical and mental health;
      this is particularly true for older people who may spend more time at home. Older
      people in social (i.e., public) housing are particularly vulnerable. Housing
      options for older people in social housing include standard design dwellings or
      specially designed "sheltered housing." The most suitable housing model should be
      identified, with older people consulted in this process. Method: Survey of older
      people (aged >=60) living in standard or sheltered social housing. Data were
      analyzed using descriptive and inferential statistics in SPSS Version 22.
      Results: Overall, 380 surveys were returned (response rate = 47.2%). All older
      people had similar housing needs. Those in sheltered housing were more satisfied
      with the physical home design and reported more positive outcomes. Older people
      in standard housing were less likely to have necessary adaptations to facilitate
      aging-in-place. Discussion: Older people in standard housing reported more
      disability/illnesses, are worried about the future, and felt less safe at home.
      However, few wanted to move, and very few viewed sheltered housing as an
      alternative, suggesting limited knowledge about their housing options. Future
      social housing designs should be flexible, that is, adaptable to the needs of the
      tenants over time.

PMID- 28491915
TI  - Expectations Regarding Aging, Physical Activity, and Physical Function in Older
      Adults.
AB  - Objective: The present study examined how expectations regarding aging (ERA)
      influence physical activity participation and physical function. Method: We
      surveyed 148 older adults about their ERA (ERA-38), health-promoting lifestyles
      (HPLP-II), and self-rated health (RAND-36). We tested the mediating effect of
      physical activity on the relationships between ERA and physical function.
      Results: Positive expectations were associated with more engagement in physical
      activity (B = 0.016, p < .05) and better physical function (B = 0.521, p < .01).
      Physical activity mediated the relationship between ERA and physical function (B
      = 5.890, p < .01, indirect effect 0.092, CI = [0.015, 0.239]). Discussion: ERA
      play an important role in adoption of physically active lifestyles in older
      adults and may influence health outcomes, such as physical function. Future
      research should evaluate whether attempts to increase physical activity are more
      successful when modifications to ERA are also targeted.

PMID- 28491916
TI  - Orthoptic Treatment of Convergence Insufficiency in Parkinson's Disease: A Case
      Series.
AB  - Introduction: This study reports a case series of orthoptic treatment (OT) for
      convergence insufficiency (CI) in individuals with Parkinson's disease (PD).
      Method: We are reporting two cases of individuals with PD who completed OT for
      CI. Both had a confirmed diagnosis of CI, accompanied by CI-type symptomatology.
      They each underwent an OT program consisting of three office-based visits and 8
      weeks of home-based exercises. Treatment outcome was based on the changes
      measured pre- versus post-OT on the near point of convergence, positive fusional
      vergences, and symptomatology score. Results: The two participants successfully
      completed therapy, gained ability to converge, had fewer symptoms, and were
      satisfied with the OT-induced changes they felt in their day-to-day lives.
      Conclusion: This case series show that OT for CI in PD is possible. Further
      research is required as these results demonstrate that OT has the potential to
      improve symptomatic CI in these patients. In the meantime, the positive results
      obtained in these two cases should encourage clinicians to consider OT (a therapy
      with no/minimal risk) for CI in patients with PD whose quality of life is
      affected by this binocular dysfunction.

PMID- 28491917
TI  - Understanding the Burden Experienced by Caregivers of Older Adults Who Use a
      Powered Wheelchair: A Cross-Sectional Study.
AB  - Objective: In this study, we aimed to describe the burden of family caregivers
      providing powered wheelchair-related and overall assistance and test the
      hypotheses that caregiver burden correlates with participation, wheelchair skills
      capacity, anxiety, depression, and social support. Methods: Cross-sectional
      study. Participants included 35 family caregivers of powered wheelchair users.
      Caregivers were assessed using the Power Mobility Caregiver Assistive Technology
      Outcome Measure, Late Life Disability Instrument, Wheelchair Skills Test
      Questionnaire for caregivers, Hospital Anxiety and Depression Scale, and
      Interpersonal Support Evaluation List-12. Results: The most burdensome powered
      wheelchair assistance items were providing verbal hints/directions, needing to be
      nearby, anxiety, and fear that user may be harmed. The most burdensome overall
      assistance item was feeling limited in recreational/leisure activities. Caregiver
      burden was significantly correlated with participation limitations, anxiety,
      depression, and social support. Discussion: Caregivers experience burden for
      wheelchair-related and overall help, especially psychological burden. Such
      results have implications for the type of resources required to support family
      caregivers.

PMID- 28491919
TI  - Anterior Superior Iliac Spine to the Tibial Tuberosity Length: An Easier,
      Accurate, and Faster Method for Predicting Orogastric Tube Length in Neonates-An
      Observational Study.
AB  - Orogastric tube (OGT) procedures are done in 20% of newborn unit cases. This
      study was contemplated to work out a formula to predict OGT length in terms of
      femur length in neonates and its agreement to existing standards. In this
      observational study, OGT length was estimated using NEMU (nose-ear-mid umbilicus)
      in 53 consecutive newborns. Their anterior superior iliac spine to tibial
      tuberosity length (AS-TT) was measured and equated using linear regression
      analysis in Stata. We further verified the accuracy of the new formula and
      comparison of time taken by both the methods. Strong positive correlation was
      seen between OGT and AS-TT (r = .88). OGT length was 10.14 + 0.88 AS-TT, which
      can be used in neonatal intensive care unit newborns with greater accuracy and
      with lesser time than the classical method. Strong agreement levels were seen. AS
      TT closely relates to the femur length and can be chosen as a guide as it is
      faster when compared to other methods.

PMID- 28491918
TI  - The Studying Multiple Outcomes After Aural Rehabilitative Treatment Study: Study
      Design and Baseline Results.
AB  - Hearing loss may affect critical domains of health and functioning in older
      adults. This article describes the rationale and design of the Studying Multiple
      Outcomes After Aural Rehabilitative Treatment (SMART) study, which was developed
      to determine to what extent current hearing rehabilitative therapies could
      mitigate the effects of hearing loss on health outcomes. One hundred and forty
      five patients >=50 years receiving hearing aids (HA) or cochlear implants (CI)
      were recruited from the Johns Hopkins Department of Otolaryngology-HNS. A
      standardized outcome battery was administered to assess cognitive, social,
      mental, and physical functioning. Of the 145 participants aged 50 to 94.9 years
      who completed baseline evaluations, CI participants had significantly greater
      loneliness, social isolation, and poorer hearing and communicative function
      compared with HA participants. This study showed that standardized measures of
      health-related outcomes commonly used in gerontology appear sensitive to hearing
      impairment and are feasible to implement in clinical studies of hearing loss.

PMID- 28491921
TI  - A Rare Presentation of Encephalopathy in a 3-Year-Old Child.

PMID- 28491920
TI  - Association of Lead Levels and Cerebral Palsy.
AB  - Background: Cerebral palsy is a common motor disability in childhood. Raised lead
      levels affect cognition. Children with cerebral palsy may have raised lead
      levels, further impairing their residual cognitive motor and behavioral
      abilities. Environmental exposure and abnormal eating habits may lead to
      increased lead levels. Aims and Objectives: To measure blood lead levels in
      children with cerebral palsy and compare them with healthy neurologically normal
      children. To correlate blood lead levels with environmental factors. Material and
      Methods:Design: Prospective case-control study. Setting: Tertiary care hospital.
      Participants: Cases comprised 34 children with cerebral palsy, and controls
      comprised 34 neurologically normal, age- and sex-matched children. Methods:
      Clinical and demographic details were recorded as per proforma. Detailed
      environmental history was recorded to know the source of exposure to lead. These
      children were investigated and treated as per protocol. Venous blood was
      collected in ethylenediaminetetraacetic acid vials for analysis of blood lead
      levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption
      spectrophotometer). Data were analyzed using SPSS version 17. P < .05 was taken
      as significant. Results: Mean blood lead levels were 9.20 +/- 8.31 ug/dL in
      cerebral palsy cases and 2.89 +/- 3.04 ug/dL in their controls (P < .001). Among
      children with cerebral palsy, 19 (55.88%) children had blood lead levels >=5
      ug/dL. Lead levels in children with pica were 12.33 +/- 10.02 ug/dL in comparison
      to children with no history of pica, 6.70 +/- 4.60 ug/dL (P = .029). No
      correlation was found between hemoglobin and blood lead levels in cases and
      controls. Conclusion: In our study, blood lead levels are raised in children with
      cerebral palsy. However, further studies are required to show effects of raised
      levels in these children.

PMID- 28491922
TI  - Epidemiology of Invasive Fungal Infections at Two Tertiary Care Neonatal
      Intensive Care Units Over a 12-Year Period (2000-2011).
AB  - We conducted a retrospective review of 168 patients with invasive fungal
      infections from January 2000 to December 2011 in 2 neonatal intensive care units.
      Patients with Candida bloodstream infection (BSI, n = 152) were further analyzed.
      C albicans was the most common species overall (47%); however, there was an
      increase in non-albicans sp from 2006 to 2011. Candida BSI clearance rates were
      lower in extremely low birth weight infants (77% vs 93%, P = .01) and in patients
      with C albicans infections (77% vs 91%, P = .01). Clearance rates improved from
      2000 to 2005 (70% - 90%) to 2006 to 2011 (86% -100%). Combination antifungal use
      increased during the later years (73% vs 49%, P < .05) and in patients with end
      organ dissemination (83% vs 54%, P < .05). We concluded that extremely low birth
      weight infants and C albicans infection are factors associated with nonclearance
      of Candida BSI. Successful clearance of Candida BSI improved in 2006 to 2011,
      perhaps due to increase in non-albicans species and the use of combination
      antifungals.

PMID- 28491923
TI  - Risk Factors for Death in Bangladeshi Children Under 5 Years of Age Hospitalized
      for Diarrhea and Severe Respiratory Distress in an Urban Critical Care Ward.
AB  - Children with diarrhea hospitalized for respiratory distress often have fatal
      outcome in resource-limited settings, although data are lacking on risk factors
      for death in such children. We sought to evaluate clinical predictors for death
      in such children. In this prospective cohort study, we enrolled under-5 children
      with diarrhea admitted with severe respiratory distress to the intensive care
      unit of Dhaka Hospital of International Centre for Diarhoeal Disease Research,
      Bangladesh, from September 2014 through September 2015. We compared clinical and
      laboratory characteristics between study children those who died (n = 29) and
      those who survived (n = 62). In logistic regression analysis, after adjusting for
      potential confounders, the independent predictors for death in children
      hospitalized for diarrhea and severe respiratory distress were severe sepsis and
      hypoglycemia (P < .05 for all). Thus, recognition of these simple parameters may
      help clinicians identify children with diarrhea at risk of deaths in order to
      initiate prompt management for the better outcome, especially in resource-poor
      settings.

PMID- 28491924
TI  - The Nutrient Density of Snacks: A Comparison of Nutrient Profiles of Popular
      Snack Foods Using the Nutrient-Rich Foods Index.
AB  - Background: Although Americans receive almost a quarter of their daily energy
      from snacks, snacking remains a poorly defined and understood eating occasion.
      However, there is little dietary guidance about choosing snacks. Families,
      clinicians, and researchers need a comprehensive approach to assessing their
      nutritional value. Objective: To quantify and compare the nutrient density of
      commonly consumed snacks by their overall nutrient profiles using the Nutrient
      Rich Foods (NRF) Index 10.3. Methods: NRF Index scores were calculated for the
      top 3 selling products (based on 2014 market research data) in different snack
      categories. These NRF scores were averaged to provide an overall nutrient-density
      score for each category. Results: Based on NRF scores, yogurt (55.3), milk
      (52.5), and fruit (30.1) emerged as the most nutrient-dense snacks. Ice cream (
      4.4), pies and cakes (-11.1), and carbonated soft drinks (-17.2) emerged as the
      most nutrient-poor snacks. Conclusions: The NRF Index is a useful tool for
      assessing the overall nutritional value of snacks based on nutrients to limit and
      nutrients to encourage.

PMID- 28491925
TI  - No Camphor Toxicity in Cambodian Infants.
AB  - Thiamine deficiency and beriberi are prevalent in Cambodia, although most infants
      with nonspecific clinical symptoms of beriberi, including tachypnea, lack
      echocardiographic evidence diagnostic of the disease. Camphor activates transient
      receptor potential vanilloid 3 (TRPV3), a nonselective ion channel expressed in
      the medial preoptic nucleus of the hypothalamus and thought to be important for
      thermo-sensitivity. Because camphorated ointments are used commonly among
      Cambodian infants, we hypothesized that topical camphor modulates
      thermoregulatory behaviors, causing beriberi-simulating tachypnea, separate from
      any influence of thiamine deficiency. We assessed 9 tachypneic and 10 healthy
      infants for Tiger Balm use and for presence of camphor in whole blood. However,
      no camphor was found in blood from any infants, indicating that camphor is
      unrelated to tachypneic illness in Cambodian infants.

PMID- 28491926
TI  - A Novel Intragenic SLC16A1 Mutation Associated With Congenital Hyperinsulinism.

PMID- 28491927
TI  - Iron Supplements for Infants at Risk for Iron Deficiency.
AB  - Professional societies have published recommendations for iron dosing of preterm
      neonates, but differences exist between guidelines. To help develop standardized
      guidelines, we performed a 10-year analysis of iron dosing in groups at risk for
      iron deficiency: IDM (infants of diabetic mothers), SGA (small for gestational
      age), and VLBW premature neonates (very low birth weight, <1500 g). We analyzed
      iron dosing after red cell transfusions and erythropoiesis-stimulating agents
      (ESA). Of IDM, 11.8% received iron in the hospital; 9.8% of SGA and 27.1% of VLBW
      neonates received iron. Twenty percent of those who received iron had it started
      by day 14; 63% by 1 month. Supplemental iron was stopped after red cell
      transfusions in 73% of neonates receiving iron. An ESA was administered to 1677,
      of which 33% received iron within 3 days. This marked variation indicates that a
      consistent approach is needed, and using this report and a literature review, we
      standardized our iron-dosing guidelines.

PMID- 28491928
TI  - Pyogenic Granuloma in an Unusual Site.

PMID- 28491929
TI  - Dexmedetomidine as an Adjunct to Treat Anticholinergic Toxidrome in Children.

PMID- 28491930
TI  - Hypereosinophilic Syndrome With Eosinophilic Gastritis.

PMID- 28491931
TI  - Dopamine-System Genes and Cultural Acquisition: The Norm Sensitivity Hypothesis.
AB  - Previous research in cultural psychology shows that cultures vary in the social
      orientation of independence and interdependence. To date, however, little is
      known about how people may acquire such global patterns of cultural behavior or
      cultural norms. Nor is it clear what genetic mechanisms may underlie the
      acquisition of cultural norms. Here, we draw on recent evidence for certain
      genetic variability in the susceptibility to environmental influences and propose
      a norm sensitivity hypothesis, which holds that people acquire culture, and rules
      of cultural behaviors, through reinforcement-mediated social learning processes.
      One corollary of the hypothesis is that the degree of cultural acquisition should
      be influenced by polymorphic variants of genes involved in dopaminergic neural
      pathways, which have been widely implicated in reinforcement learning. We
      reviewed initial evidence for this prediction and discussed challenges and
      directions for future research.

PMID- 28491932
TI  - Transition to resistance: An unexpected role of the EMT in cancer
      chemoresistance.
AB  - Two recent studies provide intriguing evidence that challenges the role of the
      epithelial-mesenchymal transition (EMT) as a critical mediator of cancer
      metastasis, while revealing an unexpected role in cancer drug resistance.1,2
      While these findings may not settle the EMT's role in metastasis, these studies
      suggest that targeting the EMT may inhibit both cancer metastasis and
      chemoresistance.

PMID- 28491934
TI  - Data on anti-insulation detection via Point of Thermal Inflexion (PTI) in 1248
      cases; 13 climates, four occupancy profiles, six wall configurations and four
      insulation levels.
AB  - The data in this article are the simulation results of 1248 cases that were
      carried out to detect anti-insulation behaviour in the article titled "Anti
      insulation mitigation by altering the envelope layers' configuration" (Idris and
      Mae, 2017) [1]. These cases are generated by a matrix of 13 climates, 6 envelope
      layer configurations, 4 occupancy profiles and 4 levels of insulation thickness.
      The data are concerned with the annual cooling and heating loads of these cases.
      In addition, the data include the Point of Thermal Inflexion (PTI) values and
      their anti-insulation pattern, when PTI is found. The PTI values are compiled in
      a single summary file and supplied as well. All These data are shared via this
      article where they can be reused in different ways, but mainly for serving
      researchers that intend to approach anti-insulation behaviour from different
      points of view.

PMID- 28491935
TI  - Numerical dataset for analyzing the performance of a highly efficient ultrathin
      film CdTe solar cell.
AB  - The article comprises numerical data of distinct semiconductor materials applied
      in the sketch of a CdTe absorber based ultrathin film solar cell. Additionally,
      the contact layer parametric values of the cell have been described also.
      Therefore, the simulation has been conducted with data related to the hetero
      structured (n-ZnO/n-CdS/p-CdTe/p-ZnTe) semiconductor device and a J-V
      characteristics curve was obtained. The operating conditions have also been
      recorded. Afterward, the solar cell performance parameters such as open circuit
      voltage (Voc), short circuit current density (Jsc), fill factor (FF), and
      efficiency (eta) have been investigated and compared with reference cell.

PMID- 28491936
TI  - Data on spatiotemporal urban sprawl of Dire Dawa City, Eastern Ethiopia.
AB  - The data presented in this paper shows the spatiotemporal expansion of Dire Dawa
      City (eastern Ethiopia) and the ensuing land use land cover changes in its peri
      urban areas between 1985 and 2015. The data were generated from satellite images
      of Thematic Mapper (TM), Enhanced Thematic Mapper-Plus (ETM+) and OLI
      (Operational Land Image) with path/raw value of 166/053 by using Arc GIS 10.1
      software. The precision of the images was verified by geolocation data collected
      from ground control points by using Geographic Positioning System (GPS) receiver.
      Four LULC classes (built up area, vegetation, barren land and farmland) with
      their respective spatiotemporal dimensions were clearly identified in the
      analysis. Built up area had shown an overall annual increment of 15.8% (82 ha per
      year) from 517 ha in 1985 to 2976 ha in 2015. Expansion took place in all
      directions but it was more pronounced along the main road towards other nearby
      towns, recently established business/service areas and the Industrial Park.
      Barren land, farmland and vegetation areas showed speedy decline over the years.

PMID- 28491937
TI  - Longitudinal multiple sclerosis lesion segmentation data resource.
AB  - The data presented in this article is related to the research article entitled
      "Longitudinal multiple sclerosis lesion segmentation: Resource and challenge"
      (Carass et al., 2017) [1]. In conjunction with the 2015 International Symposium
      on Biomedical Imaging, we organized a longitudinal multiple sclerosis (MS) lesion
      segmentation challenge providing training and test data to registered
      participants. The training data consists of five subjects with a mean of 4.4 (+/
      0.55) time-points, and test data of fourteen subjects with a mean of 4.4 (+/
      0.67) time-points. All 82 data sets had the white matter lesions associated with
      multiple sclerosis delineated by two human expert raters. The training data
      including multi-modal scans and manually delineated lesion masks is available for
      download. In addition, the testing data is also being made available in
      conjunction with a website for evaluating the automated analysis of the testing
      data.

PMID- 28491933
TI  - Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in
      Dental Tissue Engineering.
AB  - Tooth is a complex hard tissue organ and consists of multiple cell types that are
      regulated by important signaling pathways such as Wnt and BMP signaling. Serious
      injuries and/or loss of tooth or periodontal tissues may significantly impact
      aesthetic appearance, essential oral functions and the quality of life.
      Regenerative dentistry holds great promise in treating oral/dental disorders. The
      past decade has witnessed a rapid expansion of our understanding of the
      biological features of dental stem cells, along with the signaling mechanisms
      governing stem cell self-renewal and differentiation. In this review, we first
      summarize the biological characteristics of seven types of dental stem cells,
      including dental pulp stem cells, stem cells from apical papilla, stem cells from
      human exfoliated deciduous teeth, dental follicle precursor cells, periodontal
      ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and
      MSCs from gingiva. We then focus on how these stem cells are regulated by bone
      morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays
      between these pathways. Lastly, we analyze the current status of dental tissue
      engineering strategies that utilize oral/dental stem cells by harnessing the
      interplays between BMP and Wnt pathways. We also highlight the challenges that
      must be addressed before the dental stem cells may reach any clinical
      applications. Thus, we can expect to witness significant progresses to be made in
      regenerative dentistry in the coming decade.

PMID- 28491939
TI  - Data on water consumption in streptozotocin-induced diabetic mice by a novel
      peach gum-derived polysaccharide.
AB  - The data presented in this article are related to the article entitled "The
      impact of a novel peach gum-derived polysaccharide on postprandial blood glucose
      control in streptozotocin-induced diabetic mice" (Wang et al., 2017) [1].
      Polydipsia was one of the most important symptoms of diabetic mellitus (DM) mice,
      which showed more water consumption than normal ones. The water consumption of DM
      mice in different groups administrated with metformin hydrochloride or a novel
      polysaccharide (coded as PGPSD) were exhibited in this article (Fig. 1). The
      field data set is made publicly available to enable critical or extended
      analyzes.

PMID- 28491938
TI  - Synthesis of practical red fluorescent probe for cytoplasmic calcium ions with
      greatly improved cell-membrane permeability.
AB  - In this data article, we described the detailed synthetic procedure and the
      experimental data for the synthesis of a red-fluorescent probe for calcium ions
      (Ca2+) with improved water solubility. This Ca2+ red-fluorescent probe CaTM-3 AM
      could be applied to fluorescence imaging of physiological Ca2+ concentration
      changes in not only live cells, but also brain slices, with high cell-membrane
      permeability leading to bright fluorescence in biosamples. The data provided
      herein are in association with the research article "The Development of Practical
      Red Fluorescent Probe for Cytoplasmic Calcium Ions with Greatly Improved Cell
      membrane Permeability" in Cell Calcium (Hirabayashi et al., 2016) [1].

PMID- 28491940
TI  - Data on eleven sesquiterpenoids from the cultured mycelia of Ganoderma capense.
AB  - The data included in this paper are associated with the research article entitled
      "Sesquiterpenoids from the cultured mycelia of Ganoderma capense" [1]. 1H NMR,
      13C NMR, DEPT, HSQC, 1H-1H COSY, HMBC, NOESY, HRESIMS, and IR spectra of
      Ganodermanol A-H (1-11), together with Mo2(AcO)4-induced CD spectrum of
      Ganodermanol A, CD spectra of Ganodermanol D-E were included in the Data in Brief
      article. In addition, the cytotoxicities and anti-HIV-1 activity of isolated
      compounds were also included in the Data in Brief article.

PMID- 28491941
TI  - Dataset of water activity measurements of alcohol:water solutions using a Tunable
      Diode Laser.
AB  - The data presented in this article are related to the research article entitled
      "RH-temperature phase diagrams of hydrate forming deliquescent crystalline
      ingredients" (Allan and Mauer, 2017) [1]. The data are water activity
      measurements of alcohol:water solutions (methanol:water and ethanol:water
      solutions at varying molar ratios) at different temperatures collected using the
      Tunable Diode Laser by Decagon Devices. The measured water activities of
      ethanol:water solutions were correlated to the initial volumetric ratios to
      produce polynomial equations that can be used to calculate the needed initial
      volumetric ratios for water activity controlled solutions. The data sets and
      polynomial equations are provided to enable extended analyses and applications of
      the data and calculations for generating and using controlled water activity
      solutions containing alcohol. An example application of these data is described
      in the research article mentioned above.

PMID- 28491942
TI  - A dataset of multi-contrast population-averaged brain MRI atlases of a
      Parkinson's disease cohort.
AB  - Parkinson's disease (PD) is a neurodegenerative disease that primarily affects
      the motor functions of the patients. Research and surgical treatment of PD (e.g.,
      deep brain stimulation) often require human brain atlases for structural
      identification or as references for anatomical normalization. However, two
      pitfalls exist for many current atlases used for PD. First, most atlases do not
      represent the disease-specific anatomy as they are based on healthy young
      subjects. Second, subcortical structures, such as the subthalamic nucleus (STN)
      used in deep brain stimulation procedures, are often not well visualized. The
      dataset described in this Data in Brief is a population-averaged atlas that was
      made with 3 T MRI scans of 25 PD patients, and contains 5 image contrasts: T1w
      (FLASH & MPRAGE), T2*w, T1-T2* fusion, phase, and an R2* map. While the T1w,
      T2*w, and T1-T2* fusion templates provide excellent anatomical details for both
      cortical and sub-cortical structures, the phase and R2* map contain bio-chemical
      features. Probabilistic tissue maps of whiter matter, grey matter, and
      cerebrospinal fluid are provided for the atlas. We also manually segmented eight
      subcortical structures: caudate nucleus, putamen, globus pallidus internus and
      externus (GPi & GPe), thalamus, STN, substantia nigra (SN), and the red nucleus
      (RN). Lastly, a co-registered histology-derived digitized atlas containing 123
      anatomical structures is included. The dataset is made freely available at the
      MNI data repository accessible through the link
      http://nist.mni.mcgill.ca/?p=1209.

PMID- 28491943
TI  - Data on spatiotemporal land use land cover changes in peri-urban Addis Ababa,
      Ethiopia: Empirical evidences from Koye-Feche and Qilinto peri-urban areas.
AB  - Urban expansion is one of the key problems in Ethiopia resulting in displacement
      of the rural people inhabiting areas bordering the cities/towns. It is also
      resulting in land use land cover (LULC) changes affecting the livelihoods of the
      people and the ecosystems [1], [2]. The data presented in this article,
      therefore, shows the spatiotemporal LULC changes of peri-urban expansion areas
      known as Koye-Feche and Qilinto, around Addis Ababa City (the capital of
      Ethiopia). The data were generated from Landsat Thematic Mapper (TM) and Enhanced
      Thematic Mapper Plus (ETM+) images (with path/row numbers 168/054) by using ERDAS
      EMAGINE 2014 software. The precision of the images was verified by geolocation
      data collected from ground control points by using Geographic Positioning System
      (GPS) receiver. The data indicate that the built-up areas have increased by
      1017.85 ha (10.178 km2) with 89.1%, 58.4%, 47% and 13% decline of plantation
      (mostly eucalyptus woodlots), grasslands, riverine vegetation (forestland) and
      cropland, respectively, between 1986 and 2016.

PMID- 28491944
TI  - Data on cardiovascular and pulmonary diseases among smokers of menthol and non
      menthol cigarettes compiled from the National Health and Nutrition Examination
      Survey (NHANES), 1999-2012.
AB  - This Data in Brief contains results from three different survey logistic
      regression models comparing risks of self-reported diagnoses of cardiovascular
      and pulmonary diseases among smokers of menthol and non-menthol cigarettes.
      Analyses employ data from National Health and Nutrition Examination Survey
      (NHANES) cycles administered between 1999 and 2012, combined and in subsets. Raw
      data may be downloaded from the National Center for Health Statistics. Results
      were not much affected by which covariates were included in the models, but
      depended strongly on the NHANES cycles included in the analysis. All three models
      returned elevated risk estimates for three endpoints when they were run in
      individual NHANES cycles (congestive heart failure in 2001-02; hypertension in
      2003-04; and chronic obstructive pulmonary disease in 2005-06), and all three
      models returned null results for these endpoints when data from 1999-2012 were
      combined.

PMID- 28491945
TI  - Reference values for T, B and NK human lymphocyte subpopulations in adults.
AB  - The data presented in this paper are reference ranges for frequencies of thirty
      eight subpopulations of T, B and NK lymphocytes, established from a cohort of 253
      healthy blood donors aged from 19 to 67. When relevant, the influence of age or
      sex was taken into account to calculate these reference values. This article is
      related to the research article entitled "Influence of age, sex and HCMV
      serostatus on blood lymphocyte subpopulations in healthy adults" (Apoil et al.,
      2017) [1]. Immunophenotyping data obtained from each individual is made publicly
      available for extended analyses.

PMID- 28491947
TI  - Welcome to the New International Journal of Women's Dermatology.

PMID- 28491946
TI  - Technique of ICG-guided Targeted Compartmental Pelvic Lymphadenectomy (TCL)
      combined with Pelvic Peritoneal Mesometrial Resection (PMMR) for locoregional
      control of endometrial cancer - A proposal.
AB  - *PMMR is a compartment based radical hysterectomy in endometrial cancer.*Pelvic
      PMMR may be combined with ICG guided Targeted Compartmental Lymphadenectomy
      (TCL).*Video of Pelvic PMMR and TCL technique may be basis for a prospective
      study.

PMID- 28491948
TI  - The Women's Dermatology Society: Physicians, Leaders, Mentors.

PMID- 28491950
TI  - Clinical and bacteriological efficacy of twice daily topical retapamulin ointment
      1% in the management of impetigo and other uncomplicated superficial skin
      infections.
AB  - BACKGROUND: Cutaneous bacterial infections are common in children and adults and
      frequently are caused by Staphylococcus aureus (S. aureus). Treatment failures
      with topical agents are not uncommon and have been shown to be secondary to
      bacterial resistance. OBJECTIVE: To determine clinical and bacteriological
      efficacy of retapamulin ointment 1% in treatment of patients with cutaneous
      bacterial infections caused by methicillin-resistant S. aureus (MRSA) and other
      bacteria. METHODS: Prospective, nonrandomized, uncontrolled, open label, single
      center trial conducted between April 2008 and November 2012 that evaluated
      efficacy of retapamulin ointment 1% in the treatment of impetigo, folliculitis,
      and other minor soft tissue infections in children and adults. Fifty patients,
      who presented to a dermatology outpatient clinic and were clinically diagnosed
      with impetigo, folliculitis, or minor soft tissue infection suitable for
      treatment with a topical antibiotic, were screened. Thirty-eight patients were
      enrolled and received treatment: topical retapamulin ointment 1% twice daily for
      5 days. Seven patients were MRSA positive and qualified for the primary efficacy
      population. One patient withdrew due to an adverse event. Clinical and
      microbiological exams were performed at baseline and follow-up 5 to 7 days later
      to assess clinical, microbiological, and therapeutic responses. Primary outcome
      was clinical response at follow-up in primary efficacy population with MRSA
      isolated as the baseline pathogen. Secondary outcomes included clinical,
      microbiologic, and therapeutic responses in patients who were culture positive
      for any species of bacteria. RESULTS: Clinical response at follow-up in the
      primary efficacy population (MRSA-positive patients) was not sufficiently powered
      to demonstrate significance; however, outcomes were excellent, with 7 of 7
      patients demonstrating clinical success (5 of 7) or clinical improvement (2 of 7)
      at follow-up. Barring lack of significance due to small total sample size for
      patients who were culture positive for any species of bacteria (n = 35), overall
      success rates were favorable for clinical, microbiologic, and therapeutic
      responses with values of 66%, 97%, and 69%, respectively. Adverse events (AEs)
      were mild or moderate in severity. No serious AEs were reported. CONCLUSION:
      Safety profile appears favorable given the low number of AEs. Study design limits
      conclusions that can be drawn. Nevertheless, this study supports use of topical
      retapamulin 1% ointment in treatment of cutaneous bacterial infections,
      particularly those caused by S. aureus, including MRSA.

PMID- 28491949
TI  - Autoimmune blistering diseases in females: a review.
AB  - The autoimmune blistering diseases (AIBDs) are a group of heterogeneous skin
      diseases with autoantibodies directed against structural proteins in the skin. A
      new interest in the female bias towards autoimmune diseases in general has led to
      our attention to focus on how and why this female bias manifests in AIBD. The
      authors aim to review and explore the various aspects of AIBD affecting females
      more than males, including the higher prevalence, worse quality of life, and
      complex management issues such as pregnancy and lactation.

PMID- 28491951
TI  - Retrospective evidence on outcomes and experiences of pregnancy and childbirth in
      epidermolysis bullosa in Australia and New Zealand.
AB  - BACKGROUND: Pregnancy in epidermolysis bullosa (EB) has not been comprehensively
      studied. OBJECTIVE: We aimed to develop a foundational database, which could
      provide peri-obstetric advice in EB. METHODS: Survey questionnaires were sent to
      obstetricians, unaffected mothers of EB babies, and mothers with EB. Results were
      analyzed using chi-square, Fisher exact, and t-tests. RESULTS: Out of 1346
      obstetricians surveyed, 195 responded, and only 14 had encountered EB. All
      recommended normal vaginal delivery (NVD), except for one elective Caesarean
      section (CS). We received responses from 75 unaffected mothers who had delivered
      EB babies. They had significantly more complications in their EB pregnancies
      compared to their non-EB pregnancies. A further 44 women with various types of EB
      who had given birth responded. Most delivered via NVD and had no significant
      increase in complications in both their EB and non-EB pregnancies. In both
      groups, there were no significant differences in blistering at birth in babies
      delivered via NVD and CS. CONCLUSION: In conclusion, most patients with EB who
      are capable of giving birth do not have an increased risk for pregnancy-related
      complications and NVD appears to be safe. Awareness of this data amongst
      obstetricians and dermatologists should lead to improved quality of care for
      mothers and babies affected with EB.

PMID- 28491952
TI  - Dermatologic conditions in internationally adopted children.
AB  - Over 200,000 children have been adopted into United States (US) families from
      abroad since the year 2000. Health care providers who care for children adopted
      internationally should be aware of the spectrum of illnesses seen in this
      population, and should be prepared to encounter potentially unusual situations.
      An appreciation for the unique pre-adoption exposures and vulnerabilities
      inherent in international adoption is critical for proper diagnosis and treatment
      of this heterogeneous group of children. It is important to consider the impact
      of potential early childhood stressors such as nutritional, sensory, and
      emotional deprivation, trauma and abuse, as well as prenatal exposures to drugs,
      alcohol, and infectious diseases. Providers must also take into account
      international variation in health care practices, including immunization,
      treatment, surgical, and hygiene standards. The differential diagnosis for
      cutaneous eruptions in children adopted internationally is broad and must
      encompass endemic systemic illnesses with skin manifestations, such as measles,
      tuberculosis, leprosy, and congenital syphilis, and primary dermatologic diseases
      such as scabies and bacterial and fungal infections. The importance of
      maintaining a broad differential and open mind when addressing the dermatologic
      needs of these children cannot be overemphasized.

PMID- 28491953
TI  - Prevalence of anemia in patients with epidermolysis bullosa registered in
      Australia.
AB  - BACKGROUND: Anemia is a common complication of epidermolysis bullosa (EB). To
      date, no extensive data on the prevalence of anemia in EB patients have been well
      characterized worldwide. OBJECTIVE: To determine and to characterize the
      prevalence of anemia in the Australian EB population by conducting a
      retrospective cross-sectional study. METHODS: All (n = 368) EB patients
      registered in the Australasian Epidermolysis Bullosa Registry (AEBR) from 2006 to
      2012 were reviewed for pathological evidence of anemia. Patients with EB without
      anemia and those without hematological parameters were excluded from the study.
      Patients' particulars were separated into pediatric (< 18 years old) and adult
      (>= 18 years old) male and female subgroups. RESULTS: One-hundred sixty-nine out
      of 368 EB patients had eligible blood results to be analyzed, as milder forms of
      EB did not routinely have laboratory testing; 27.8% (n = 47/169) of EB patients
      were anemic at any time point in their lifetime. All generalized severe
      junctional EB (JEB-GS) cases (100%, n = 4/4); 68.0% (n = 17/25) of recessive
      dystrophic EB (RDEB); and 37.5% (n = 6/16) of generalized intermediate JEB (JEB
      I) patients were anemic. LIMITATIONS: As EB is an orphan disease, the limited
      sample size may have affected the significance of the study result. CONCLUSION:
      The high prevalence of anemia seen in RDEB and JEB generalized severe (JEB-GS)
      patients in our cohort is similar to those reported in case series.

PMID- 28491955
TI  - Oleoma treated with oral colchicine: Report of two cases and review of the
      literature.
AB  - Oleoma is a non-allergic, foreign body type granulomatous reaction. It appears as
      response to oily exogenous substances injected to the dermis or subcutis for
      aesthetical purposes. Treatment for localized lesions is surgical. When they are
      multiple, steroids may show some result. Newer therapeutic possibilities are
      being introduced and colchicine constitutes an alternative that is financially
      accessible and safe in moderate doses for certain dermatological illnesses. We
      present two women with oleoma on the legs treated with oral colchicine. This
      option was due to the extension of the clinical picture, which would not have a
      good surgical outcome. There was significant improvement in one patient, while we
      had to interrupt the medication in the other because of side effects.

PMID- 28491954
TI  - A systematic review of patients with Merkel cell carcinoma of the head and neck
      and a negative sentinel lymph node biopsy.
AB  - BACKGROUND: A negative sentinel lymph node biopsy (SLNB) from patients with head
      and neck Merkel cell carcinoma (HNMCC) may allow the patient to avoid further
      adjunctive therapies. However, there is considerable regional variability of
      lymphatic drainage from primary sites involving the head and neck, and Merkel
      cell carcinoma (MCC) has aggressive biologic behavior. OBJECTIVE: The primary aim
      of this systematic review was to document the incidence of regional recurrence
      and mortality from HNMCC patients after a negative SLNB. METHODS: A systematic
      search of the English literature was conducted via Ovid Medline and Embase from
      inception until 2013 and the Cochrane Central Register of Controlled Trials from
      1991 to January 2014. RESULTS: Twenty-three studies, with a total of 81 patients
      matched the inclusion criteria. The incidence of regional recurrence from the
      entire cohort was 12.3%, and there was a 5% mortality rate. The mean follow-up
      time, excluding the 30 patients who did not have individual follow-up times
      specified, was 32.8 months. LIMITATIONS: This review included studies had
      variable follow-up durations and treatments for MCC. CONCLUSIONS: Despite
      negative pathologic staging of the neck using SLNB in HNMCC patients, there is
      still a high incidence of regional recurrence and mortality, over a short follow
      up period.

PMID- 28491957
TI  - Maternity and medical leave during residency: Time to standardize?

PMID- 28491956
TI  - Nontuberculous mycobacterial infections: a potential complication of cosmetic
      procedures.
AB  - Interest in surgical and non-surgical cosmetic procedures has increased
      significantly over the last few decades. Billions of dollars are spent on these
      procedures annually. Although the associated risk is generally low, multiple
      cases of skin and soft tissue infections have been reported. Nontuberculous
      mycobacteria (NTM), in particular M. chelonae, M. fortuitum, and M. abscessus,
      have been increasingly identified as causative of numerous cosmetic procedure
      related infections worldwide. This has therefore become a public health concern.
      Delays in diagnosis and appropriate management may occur given subtleties in
      diagnostic methods. The purpose of this review is to highlight the NTM-related
      skin and soft tissue infections associated with more common cosmetic procedures,
      describe methods of identification, and outline best treatment practices.

PMID- 28491958
TI  - Maternity Leave for Residents and Young Attendings.

PMID- 28491959
TI  - Maternity leave: how to make it fairer for all.

PMID- 28491961
TI  - Updates in the understanding and treatments of skin and hair disorders in women
      of color.

PMID- 28491962
TI  - Skin needling as a treatment for acne scarring: An up-to-date review of the
      literature.
AB  - BACKGROUND: Skin needling is a technique used to improve the appearance of acne
      scarring. OBJECTIVE: To comprehensively review the medical literature regarding
      skin needling as a treatment for acne scarring. METHODS: A literature search was
      performed using the PubMed, Medline, and Embase databases, in addition to
      reviewing the bibliographies of relevant articles. RESULTS: Ten studies presented
      patients treated with skin needling alone, while eight studies discussed skin
      needling in combination with other treatments for acne scarring. All studies
      showed improvements in scarring after needling, with 12 reporting statistical
      significance. The median number of treatments when needling was used alone was
      three, the median duration between treatments was 4 weeks, and the median needle
      length used was 1.5 mm. Reported adverse events were infrequent and included post
      inflammatory hyperpigmentation, "tram track" scarring, acne, and milia. There
      were no reports of bacterial infections. LIMITATIONS: The studies reviewed were
      heterogeneous in design and of variable validity, with some not reporting
      statistical significance. CONCLUSION: There is moderate evidence to suggest that
      skin needling is beneficial and safe for the treatment of acne scarring. However,
      double-blinded, randomized controlled trials are required to make more definitive
      conclusions.

PMID- 28491960
TI  - Updates in the understanding and treatments of skin & hair disorders in women of
      color.
AB  - Skin of color comprises a diverse and expanding population of individuals. In
      particular, women of color represent an increasing subset of patients who
      frequently seek dermatologic care. Acne, melasma, and alopecia are among the most
      common skin disorders seen in this patient population. Understanding the
      differences in the basic science of skin and hair is imperative in addressing
      their unique needs. Despite the paucity of conclusive data on racial and ethnic
      differences in skin of color, certain biologic differences do exist, which affect
      the disease presentations of several cutaneous disorders in pigmented skin. While
      the overall pathogenesis and treatments for acne in women of color are similar to
      Caucasian men and women, individuals with darker skin types present more
      frequently with dyschromias from acne, which can be difficult to manage. Melasma
      is an acquired pigmentary disorder seen commonly in women with darker skin types
      and is strongly associated with ultraviolet (UV) radiation, genetic factors, and
      hormonal influences. Lastly, certain hair care practices and hairstyles are
      unique among women of African descent, which may contribute to specific types of
      hair loss seen in this population, such as traction alopecia, trichorrhexis
      nodosa and central centrifugal cicatricial alopecia (CCCA).

PMID- 28491963
TI  - Nail changes in female pemphigus vulgaris patients on immunosuppressive therapy.
AB  - BACKGROUND: Pemphigus vulgaris (PV) patients receiving immunosuppressive therapy
      may develop nail alterations resulting from infection, skin disorder, or drug
      regimen. OBJECTIVE: This study aims to describe nail changes in PV female
      patients receiving immunosuppressive therapy and to report the frequency of
      associated fungal and bacterial growth in the patients' nails. METHODS: Twenty
      five female PV patients who had at least one acquired finger or toenail
      abnormality and had been administered at least one immunosuppressive drug were
      included in the study. Nail alterations were recorded. Nail scrapings were
      collected from abnormal nails for fungal and bacterial examination. RESULTS:
      Positive fungal and bacterial cultures were detected in 20 (80%) of patients'
      nail samples. Five patients reported nail alterations coinciding with disease
      onset, whereas 13 reported nail changes after administration of immunosuppressive
      therapy. LIMITATIONS: Lack of a control group (patients on similar
      immunosuppressive medications for conditions other than PV) which would have
      further supported the findings demonstrated in this observational study.
      CONCLUSION: Nail abnormalities in severe PV patients are frequently associated
      with fungal and bacterial growth. Immunosuppressive therapy potentially initiates
      such changes.

PMID- 28491964
TI  - The effect of probiotics on immune regulation, acne, and photoaging.
AB  - Probiotics are live micro-organisms that provide a health benefit to the host.
      The role of probiotics in the management of disease, as well as immune
      modification, has recently experienced a renewed interest in society, as
      probiotics can be found in products ranging from yogurt to facial creams. In this
      article, we discuss the role of probiotics in the development of the immune
      system, the treatment of acne and rosacea, and protection against aging and
      photodamage.

PMID- 28491965
TI  - Endocrine evaluation of hirsutism.
AB  - Hirsutism is defined as excessive terminal hair growth in a male pattern in
      females. It typically affects 5 to 10% of reproductive-age women. Excessive hair
      growth can often cause significant psychological and emotional distress. As a
      result, hirsutism is a common presenting complaint to healthcare professionals,
      including dermatologists, as women search for cosmetic and medical solutions to
      their problem. Hirsutism results from excess production of androgens, often from
      ovarian or adrenal sources. It is typically associated with a metabolic syndrome
      like polycystic ovarian syndrome (PCOS), but can be idiopathic or medication
      induced. This article provides an endocrine perspective for the evaluation and
      management of hirsutism.

PMID- 28491966
TI  - Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative
      cheilitis.
AB  - BACKGROUND: Exfoliative cheilitis is a condition of unknown etiology
      characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic
      desquamation. It remains largely refractory to treatment, including
      corticosteroid therapy, antibiotics, antifungals, and immunosuppressants.
      OBJECTIVE: We sought to evaluate the safety and efficacy of excimer laser therapy
      and narrowband ultraviolet B therapy in female patients with refractory
      exfoliative cheilitis. METHODS: We reviewed the medical records of two female
      patients who had been treated unsuccessfully for exfoliative cheilitis. We
      implemented excimer laser therapy, followed by hand-held narrowband UVB
      treatments for maintenance therapy, and followed them for clinical improvement
      and adverse effects. RESULTS: Both patients experienced significant clinical
      improvement with minimal adverse effects with excimer laser therapy 600-700
      mJ/cm2 twice weekly for several months. The most common adverse effects were
      bleeding and burning, which occurred at higher doses. The hand-held narrowband
      UVB unit was also an effective maintenance tool. LIMITATIONS: Limitations include
      small sample size and lack of standardization of starting dose and dose
      increments. CONCLUSION: Excimer laser therapy is a well-tolerated and effective
      treatment for refractory exfoliative cheilitis with twice weekly laser treatments
      of up to 700 mJ/cm2. Transitioning to the hand-held narrowband UVB device was
      also an effective maintenance strategy.

PMID- 28491967
TI  - The history of dermatology at the Woman's Medical College of Pennsylvania.
AB  - There is little written about the history of women in dermatology. In this paper,
      we summarize the information obtained from archival records from the Woman's
      Medical College of Pennsylvania, one of the first medical schools for women,
      where several of the early prominent women in dermatology obtained their medical
      degrees and practiced. Among others, graduates include Rose Hirschler, MD, and
      Margaret Gray Wood, MD. The school and its graduates made important contributions
      to dermatology and to the advancement of women in the field. The history of women
      in dermatology is not well documented, and this historical research provides
      background in the biographies of pioneering women in an effort to preserve and
      honor their important work.

PMID- 28491969
TI  - The German experiment: Health care without female or Jewish doctors.
AB  - Jewish and female doctors were not allowed to practice medicine in Germany during
      Hitler's rule from 1933 to 1945. Data about the consequences of this on the
      health service are difficult to come by, but what information can be gathered
      demonstrates a detrimental effect on the nation's health. These data, however,
      must be interpreted with consideration to the morbidity and mortality from
      violence, death camps, slave labor, and the privations of war. The article
      summarizes the history of German health care during this period and also compares
      Germany to other nations at that time.

PMID- 28491970
TI  - Mentoring and the U.K. Medical Women's Federation.

PMID- 28491968
TI  - The immunologic effects of estrogen on psoriasis: A comprehensive review.
AB  - BACKGROUND: Immunological changes in pregnancy are associated with improvements
      in some pre-existing immune-mediated skin diseases. Estrogen has been
      hypothesized to contribute to these changes by creating a shift from Th1 and Th17
      to Th2 immunity. As this hypothesis would predict, psoriasis (a primarily Th17
      mediated immune disease) tends to improve during pregnancy. However, the precise
      mechanism by which estrogen induces immunological change in psoriasis remains
      poorly understood. OBJECTIVE: To summarize the immunologic effects of estrogen as
      they relate to psoriasis during pregnancy. METHODS: We performed an English
      language PubMed search of articles from September 2004 to September 2014
      combining the key terms "psoriasis," "estrogen," "autoimmune disease," and
      "pregnancy." RESULTS: Estrogen appears to up-regulate Th2 cytokines and down
      regulate Th1 and Th17 cytokines. This shift was initially observed in murine
      systems, which showed decreased mixed lymphocyte reactions of splenocytes and
      increased antibody production during pregnancy. Antigen stimulated splenocytes
      produced fewer Th1 cytokines and more Th2 cytokines in pregnant mice. IL17
      producing T cells were significantly decreased in healthy pregnancies compared to
      non-pregnant controls. LIMITATIONS: This review is limited by the paucity of
      studies evaluating immunological changes of psoriasis in pregnancy among human
      subjects. CONCLUSIONS: Increased estrogen production in pregnancy is associated
      with decreased Th1 and Th17 cytokine production. While estrogen may be
      responsible for some of these immune shifts resulting in disease improvement,
      there remains no definitive evidence to prove the hypothesis that estrogen is
      responsible for such improvement.

PMID- 28491971
TI  - Mentorship: A key mission of the Women's Dermatologic Society.

PMID- 28491972
TI  - History of Women in Dermatology series.

PMID- 28491973
TI  - Dr. Wilma Fowler Bergfeld: A woman of substance, role model, and founder of the
      Women's Dermatologic Society.

PMID- 28491974
TI  - Skin cancer concerns particular to women.
AB  - BACKGROUND: Skin cancer has reached epidemic proportions, with more new cases
      diagnosed annually than the combined incidence of cancers of the breast,
      prostate, lung, and colon. Estimates show 2 to 3 million new cases of non
      melanoma skin cancer (NMSC) every year, and, among women, it is the young
      (younger than 45 years) who are disproportionately affected. OBJECTIVE: This
      article aims to address questions and concerns pertinent to skin cancer in a
      woman-centric way. An updated landscape of causative factors, the latest
      detection/treatment methods, and ultimately the preventative measures available
      to them are described. METHODS: A broad literature search was conducted using the
      PubMed database with search terms focusing on female gender. Additional articles
      were identified from cited references. CONCLUSIONS: The published findings on
      causation of melanoma skin cancer and non-melanoma skin cancer in females are
      outlined, as well as current detection methods and treatment options.
      Furthermore, a variety of preventative measures specific to women that can reduce
      the chance of being diagnosed with skin cancer are discussed.

PMID- 28491975
TI  - Mid-dermal elastolysis: A female-centric disease; case report and updated review
      of the literature.
AB  - BACKGROUND: Mid-dermal elastolysis (MDE) is a rare, yet well-defined clinical and
      histopathologic entity manifested by fine wrinkling of the skin and mid-dermal
      loss of elastic fibers. This disease predominantly affects young to middle-aged
      Caucasian females and although it has no reported systemic features, it is
      psychologically bothersome and can be of great cosmetic concern. METHODS: We
      report a case of a healthy 45 year-old female with widespread mid-dermal
      elastolysis. A literature search using the search terms "mid-dermal elastolysis,"
      "mid dermal elastolysis," "middermal elastolysis," and "elastophagocytosis" was
      conducted on Pubmed, using articles published from January 2008 until November
      2014 to accompany Gambichler's comprehensive 1977 to 2009 review of mid-dermal
      elastolysis. The references of relevant papers were reviewed and further cases
      included as appropriate. RESULTS: We review the clinical features and
      histological, ultrastructural, and immunohistochemical findings of MDE, as well
      as differential diagnoses. There are 13 new publications of MDE since 2008. The
      novel findings since Gambichler's review are discussed and pathomechanisms
      revisited. Interestingly, given the striking female predominance of MDE, there is
      no known hormonal role in its etiology.

PMID- 28491976
TI  - Infiltrated papules on the trunk and headaches: A case of actinic granuloma and a
      review of the literature.
AB  - Actinic granuloma is a rare granulomatous reaction that is more commonly seen in
      females and thought to occur as an autoimmune response to actinic damage of
      elastic tissue. We discuss a case of a patient with actinic granuloma presenting
      with concomitant temporal arteritis. Our case and review of the literature
      emphasize the association between actinic granuloma and temporal arteritis, a
      serious inflammatory condition that could lead to blindness if misdiagnosed.

PMID- 28491977
TI  - De Sanctis-Cacchione syndrome: A case report and literature review.
AB  - De Sanctis-Cacchione (DSC) syndrome is one of the rarest, most severe forms of
      xeroderma pigmentosum (XP). These patients with XP are of short stature, have
      mental disabilities, and develop progressive neurologic degeneration because of a
      severe inability to repair damaged DNA. Herein, we will present the case of a 9
      year-old boy who had DSC syndrome with microcephaly, severe psychomotor
      retardation, ataxia, and hearing loss. The cutaneous manifestations included
      giant squamous cell carcinoma (SCC) that covered the eye, multiple facial SCCs,
      and pigment changes on sun-exposed areas. In addition, we include a review of
      reported rare cases and a brief discussion of disease management.

PMID- 28491978
TI  - Update on lichen planus and its clinical variants.
AB  - Lichen planus (LP) is an inflammatory skin condition with characteristic clinical
      and histopathological findings. Classic LP typically presents as pruritic,
      polygonal, violaceous flat-topped papules and plaques; many variants in
      morphology and location also exist, including oral, nail, linear, annular,
      atrophic, hypertrophic, inverse, eruptive, bullous, ulcerative, lichen planus
      pigmentosus, lichen planopilaris, vulvovaginal, actinic, lichen planus-lupus
      erythematosus overlap syndrome, and lichen planus pemphigoides. Clinical
      presentation of the rarer variant lesions may be largely dissimilar to classic LP
      and therefore difficult to diagnose based solely on clinical examination.
      However, histopathological examination of LP and LP-variant lesions reveal
      similar features, aiding in the proper diagnosis of the disease. Management of LP
      and LP variants aims to control symptoms and to decrease time from onset to
      resolution; it often involves topical corticosteroids, but varies depending on
      the severity and location of the lesion. The literature contains an array of
      reports on the variations in presentation and successful management of LP and its
      variants. A familiarity with LP and its variants is important in achieving timely
      recognition and management of the disease.

PMID- 28491979
TI  - The reliability and validity of outcome measures for atopic dermatitis in
      patients with pigmented skin: A grey area.
AB  - BACKGROUND: Outcome measures for atopic dermatitis (AD) patients with pigmented
      skin have neither been developed nor validated. OBJECTIVE: To compare the
      reliability and validity of four common AD outcome measures in patients with
      various levels of skin darkness. METHOD: The inter- and intra-rater reliability
      and construct validity of the EASI (Eczema Area and Severity Index), objective
      SCORing Atopic Dermatitis (oSCORAD), Three Items Severity index (TIS) and Six
      Areas, Six Sites Atopic Dermatitis (SASSAD) were evaluated in 18 patients of
      various levels of skin darkness, using their full body photographs, by five
      trained clinicians. RESULTS: The inter-rater reliability intraclass coefficient
      (ICCs) and 95% confidence intervals were poor for highly pigmented patients: EASI
      -.054(-.200 to .657), oSCORAD -.089(-.206 to .598), TIS -.21(-.24 to .147),
      SASSAD -.071(-.200 to .631); fair for mildly pigmented patients: EASI .464(.140
      .839), oSCORAD .588(.265-.89), TIS.524(.200-.865), SASSAD .41(.045-.775); and
      fair to good for non-pigmented patients: EASI .64(.330-.908), oSCORAD .586(.263
      .889), TIS .403(.09-.809), SASSAD .667(.358-.916). Erythema likely contributed to
      the inter-rater variability. Construct validity had significant correlations
      across all measures in non-pigmented patients, but no correlations in highly
      pigmented patients. CONCLUSION: AD outcome measures have poor reliability and
      validity in highly pigmented patients, with variations in erythema perception
      being a contributor.

PMID- 28491980
TI  - Eruptive inflamed seborrheic keratoses in the setting of endometrial
      adenocarcinoma.
AB  - Eruptive seborrheic keratoses have been reported as a rare paraneoplastic
      dermatosis in the setting of internal malignancy, particularly that of the
      digestive tract. This case illustrates a patient with a family history of gastric
      cancer who presented with an acute eruption of inflamed pruritic seborrheic
      keratoses with annular and gyrate erythema, and was found to have endometrial
      adenocarcinoma. The inflammatory cutaneous eruption resolved shortly after
      surgical removal of the dysplastic uterine tissue. This case demonstrates an
      example of a common gynecological malignancy presenting in an uncommon way; in
      the absence of uterine bleeding, the patient's skin manifestations in the form of
      a paraneoplastic dermatosis prompted timely diagnosis. Thus this case serves to
      raise awareness of cutaneous manifestations of a women's health issue, in which
      early detection can impact health outcomes.

PMID- 28491981
TI  - The women behind the names: Dermatology eponyms named after women.

PMID- 28491983
TI  - Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm
      improves quality of life in recessive dystrophic epidermolysis bullosa.
AB  - We report a 20-year-old female with generalized, severe, recessive dystrophic
      epidermolysis bullosa who developed secondary chronic anal fissures. This
      resulted in anal sphincter spasm and severe, disabling pain. She was treated with
      five botulinum toxin A injections into the internal anal sphincter over a period
      of 2 years and gained marked improvement in her symptoms. This case demonstrates
      the successful use of botulinum toxin A injections to relieve anal sphincter
      spasm and fissuring, with long-term improvement.

PMID- 28491982
TI  - What ages hair?

PMID- 28491984
TI  - Infection or allergy? The multifaceted nature of vulvar dermatoses.
AB  - Chronic dermatitis or pruritus affecting the female genital and perianal skin can
      be challenging to properly diagnose and manage. The differential diagnosis
      generally includes allergic, inflammatory, infectious, and neoplastic conditions.
      We report the case of a 52-year-old woman with a 6-month history of a
      progressive, debilitating vulvar and perianal rash that highlights the
      multifaceted nature of female genital dermatoses.

PMID- 28491986
TI  - Giant skin tag on the labium majorum.

PMID- 28491985
TI  - Anti-p200 pemphigoid (anti-laminin-gamma1 pemphigoid) demonstrating pathergy.
AB  - Anti-p200 pemphigoid, also called anti-laminin-gamma1 pemphigoid, is a recently
      defined entity. First reported in 1996, the incidence is relatively rare, with
      approximately 70 reports in the literature. Clinical presentation is
      heterogeneous, but the disease most commonly mimics bullous pemphigoid with
      urticarial papules, plaques, or tense bullae on the trunk or extremities.
      Described here is a case with additional features of pathergy that have not yet
      been reported in the literature.

PMID- 28491987
TI  - The Inaugural Dermatology Entrepreneurship Conference: Dermatologists and
      Partners Enriching the Pipeline for Innovative Products.

PMID- 28491988
TI  - Barbara A. Gilchrest: A world-renowned dermatologist and researcher, a great
      mentor, an educator, former president of the Society for Investigative
      Dermatology, editor-in-chief of The Journal of Investigative Dermatology, and a
      devoted friend.

PMID- 28491989
TI  - Professor Rona MacKie, Scottish dermatologist and melanoma authority.

PMID- 28491990
TI  - What "leaning in together" means to me.

PMID- 28491991
TI  - Chaupadi: The affliction of menses in Nepal.

PMID- 28491992
TI  - A ten-year comparison of women authorship in U.S. dermatology literature, 1999
      vs. 2009.
AB  - Women are entering medicine at increasing rates, particularly in dermatology. In
      this study, we compared women's influence and status in academic dermatology with
      that of men by examining authorship roles in peer-reviewed dermatology
      literature. We examined the literature in 2009 and compared that to 10 years
      prior (1999). A total of 1399 articles were reviewed, 594 of which met study
      criteria and were included in statistical analysis. There was a marked increase
      in senior female authorship over a decade (22% vs. 38%, p < 0.001). Female first
      authorship increased as well (41% vs. 51%, p < 0.001). In contrast, changes in
      male senior and first authorship were not statistically significant. Federal
      funding for female senior authors increased over a decade (19% vs. 37%, p =
      0.05), and female senior authors in the 2009 cohort were more likely to hold a
      dual MD/PhD degree (0% vs. 11%, p = 0.04) or pure PhD degree (11% vs. 27%, p =
      0.04). Women are approaching parity with men in terms of authorship in the
      dermatology literature, and additional research training and attainment of
      federal funding have helped women publish as senior authors.

PMID- 28491993
TI  - Understanding the new FDA pregnancy and lactation labeling rules.

PMID- 28491994
TI  - Classifying discoid lupus erythematosus: background, gaps, and difficulties.
AB  - To inform our ongoing efforts to develop defining features to be incorporated
      into a novel set of classification criteria for discoid lupus erythematosus
      (DLE), we conducted a literature review using the Ovid MEDLINE database. A search
      was performed to identify studies reporting criteria used to distinguish DLE from
      other cutaneous lupus erythematosus subtypes. We examined which clinical,
      histopathologic, and serologic features have data to support their use as
      effective features in distinguishing DLE from other potential disease mimickers
      and cutaneous lupus subsets. Through our search, we were also able to identify
      gaps that exist in the literature which can inform future directions for research
      endeavors. We found that localization of lesions, characteristic features of
      damage, and the absence of high titer Ro/SSA antibody seem most effective in
      differentiating DLE from other cutaneous lupus erythematosus subtypes.
      Histopathologic features and class of immunoreactant deposition appear to be less
      helpful.

PMID- 28491995
TI  - Dermatologic surgery on the chest wall in patients with a cardiac surgery
      history: a review of material that may be encountered intraoperatively, including
      potential complications and suggestions for proceeding safely.
AB  - BACKGROUND: Thoracic surgical procedures and the use of cardiac devices such as
      pacemakers are becoming increasingly prevalent in the population. As such,
      dermatologists may have a greater likelihood of encountering previously implanted
      or abandoned surgical material in the course of dermatologic surgery on the chest
      wall. A basic understanding of the wire types and the tunneling paths utilized in
      such procedures is important in accurately anticipating the presence of these
      wires to effectively manage any chance encounters. OBJECTIVE: We present a review
      on temporary epicardial pacing wires, temporary transvenous pacing wires,
      pacemaker leads, and surgical steel sutures in the context of dermatologic
      surgery. METHODS: A literature review was performed on frequently used wire
      material in patients with a history of cardiac surgery as well as related
      dermatologic complications from these materials. RESULTS & CONCLUSION:
      Dermatologic surgeons should particularly be aware that temporary epicardial
      pacing wires and pacemaker leads are not uncommonly abandoned in the chest wall
      of many patients. All patients with a cardiac surgery history should be
      questioned about possible retained wires. If wire material is encountered
      intraoperatively, immediately stop the procedure and do not attempt further
      manipulation of the wire until suggested steps are taken to ascertain the wire
      type.

PMID- 28491996
TI  - Amyloidosis: A story of how inframammary erosions eclipsed inconspicuous
      periorbital ecchymoses.
AB  - Systemic amyloidosis is a rare disease that can be rapidly progressive due to
      widespread organ involvement. There are well-described renal, cardiac, pulmonary,
      neurological, and dermatologic findings. Here, we outline one patient's
      experience with the condition from presentation to making the diagnosis. She
      presented with pathognomonic dermatologic findings including pinch purpura and
      ecchymoses found in the skin folds.

PMID- 28491997
TI  - The quality of dermatology consultation documentation in discharge summaries: a
      retrospective analysis.
AB  - INTRODUCTION: Good quality documentation of dermatology consults in discharge
      summaries allows diagnostic and therapeutic plans to be communicated to other
      health professionals and ensures that appropriate governmental funds are provided
      to dermatology departments. METHODS: A retrospective analysis was performed of
      all dermatology consults seen in 2013 at a public tertiary hospital in Sydney,
      Australia. RESULTS: Two hundred nineteen discharge summaries related to inpatient
      dermatology consultations were analysed; 80.6% of dermatology consults, 72.2% of
      skin biopsies, and 57.6% of diagnoses were duly included in the discharge
      summaries; 82.5% of the discharge summaries were completed before the discharge.
      The accuracy rate of diagnosis documentation was 54.5% and was correlated with
      clear dermatology team documentation, the use of a problems list, infectious skin
      diseases and junior medical staff authorship. CONCLUSION: This study highlights
      the need for improvement in dermatology consult documentation in discharge
      summaries. It suggests the use of a problems list in discharge summaries, clarity
      in dermatology teams' documentations, and postdischarge follow-up.

PMID- 28491998
TI  - Chromated copper arsenate-treated wood: a potential source of arsenic exposure
      and toxicity in dermatology.
AB  - Arsenic-contaminated drinking water presents a serious health hazard in certain
      geographic locations around the world. Chromated copper arsenate, a pesticide and
      preservative that was used to pressure treat residential lumber in the United
      States beginning in the 1940s and was banned by the Environmental Protection
      Agency in 2003, poses a potential source of arsenic exposure and toxicity. In
      this study, we review the clinical manifestations of arsenic intoxication with
      the focus on dermatologic manifestations. Dermatologists should be aware that
      although chromated copper arsenate-treated wood for residential use was banned in
      2003, the exposure risk remains. Long-term follow up is necessary to detect
      arsenic induced cutaneous and visceral malignancy in patients with history of
      arsenic exposure.

PMID- 28491999
TI  - Treatment of lateral canthal rhytides with a medium depth chemical peel with or
      without pretreatment with onabotulinum toxin type A: a randomized control trial.
AB  - BACKGROUND: Combination therapies used to treat the photoaged skin have become
      more popular as studies demonstrate greater efficacy and improved clinical
      outcomes compared to single treatment modalities. OBJECTIVES: To evaluate the
      safety and effectiveness of treating the lateral canthal rhytide complex with a
      Jessner's and 35% TCA peel with and without pretreatment with BTX-A. METHODS:
      Twenty-six subjects with Fitzpatrick skin types I -III were randomized to receive
      treatment of their lateral canthal rhytide complex with a Jessner's and 35% TCA
      peel with or without pretreatment with BTX-A. A single blinded dermatologist
      assigned a lateral canthal wrinkle score of subjects' at baseline and week 8-10.
      RESULTS: Comparison between the two treatment groups demonstrated that the group
      receiving combination treatment had significantly greater improvement in wrinkle
      reduction as compared to the group only receiving the chemical peel (P =0.002).
      In addition, there was no significant association between skin type and treatment
      groups (P = 0.11). CONCLUSIONS: These findings suggest that treating the lateral
      canthal rhytide complex with a combination of BTX-A followed by Jessner's and 35%
      TCA peel is more effective than chemical peel alone. These results are
      independent of skin type and demonstrate an additional treatment strategy for
      lateral canthal rhytides.

PMID- 28492000
TI  - Use of topical imiquimod in the treatment of VIN: a case report and review of the
      literature.
AB  - Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the vulvar
      squamous epithelium. Standard treatment for VIN lesions is surgical excision.
      Alternative therapeutic options for conservative treatment have been sought by
      patients to prevent disfigurement and to preserve sexual function. We present
      such a patient in whom topical imiquimod was used with a successful outcome.
      Imiquimod is effective in the treatment of VIN, as well as convenient, self
      administered, and generally well tolerated.

PMID- 28492001
TI  - Improving young physician membership and engagement in a dermatology physician
      organization: The Women's Dermatologic Society as a case example.

PMID- 28492002
TI  - Women's issues in the 2016 presidential election: impact on women in medicine.

PMID- 28492003
TI  - Developing classification criteria for discoid lupus erythematosus: an update
      from the World Congress of Dermatology 2015 meeting.
AB  - Currently, no standardized classification criteria exist for cutaneous lupus
      erythematosus. With increased interest in studying cutaneous lupus erythematosus,
      specifically discoid lupus erythematosus, it is our aim to apply previously
      adopted methods from rheumatology to dermatologic diseases to develop feasible,
      validated, and standardized classification criteria useful in both academic and
      community practice. Here we report the progress to date to define discoid lupus
      erythematosus using clinical, histopathologic, and serologic features by means of
      a Delphi method-using a series of iterative questionnaires sent to expert
      stakeholders. We present specific updates from the World Congress of Dermatology
      2015 meeting, at which a nominal group of expert stakeholders met to discuss the
      results of round 1 of the Delphi process to further clarify and harmonize
      specific classification items for inclusion into round 2.

PMID- 28492004
TI  - Unforeseen ethical challenges for isotretinoin treatment in transgender patients.

PMID- 28492005
TI  - Longitudinal melanonychia in an Iranian population: a study of 96 patients.
AB  - BACKGROUND: Longitudinal melanonychia (LM) can be a challenging sign since it may
      be caused by a wide variety of benign and malignant conditions. Cutaneous
      melanoma is the most important cause of LM. Objective: We performed this study to
      examine different aspects of LM in Iran, where cutaneous melanoma is rare.
      METHODS: In this cross-sectional study, we reviewed medical records and pathology
      reports of a total of 96 patients presenting with LM. These patients had been
      visited and undergone nail biopsy in Razi Hospital, Tehran University of Medical
      Sciences, Tehran, Iran. Demographic, clinical, and pathological data were
      recorded. RESULTS: The most common diagnosis was junctional nevi in 28 patients
      (29.2%) followed by melanoma in 19 patients (19.8%). Patients had a mean age of
      42.4 years (+/- 19.4). The mean ages in the groups with junctional nevi and
      melanoma were 33.3 (+/- 19.5) and 51.9 (+/- 17.8), respectively; their difference
      was statistically significant (P value = 0.001). Hutchinson's sign was present in
      10 patients, 9 of which had melanoma. Also, melanoma was only observed in
      patients presenting with a solitary nail lesion. Nails mostly affected by
      melanoma were middle fingers of the hands (7 patients) and thumbs (6 patients).
      Out of 18 patients with nail dystrophy, 13 (72.2%) were diagnosed with melanoma.
      LIMITATIONS: Only patients who have undergone biopsy were studied. CONCLUSION:
      Melanoma is an important cause of LM in Iranian patients and should especially be
      suspected in older patients who present with a solitary nail lesion on their
      middle finger or thumb. Other findings that direct us toward melanoma are
      presence of Hutchinson's sign and nail dystrophy.

PMID- 28492006
TI  - Evaluation of prolactin levels in patients with newly diagnosed pemphigus
      vulgaris and its correlation with pemphigus disease area index.
AB  - BACKGROUND: Prolactin is a hormone; in addition to it known roles, it has
      immunomodulatory effects on lymphocytes maturation and immunoglobulins
      production. Hyperprolactinemia has been demonstrated in various autoimmune
      diseases such as systemic lupus erythematosus, rheumatoid arthritis, type I
      diabetes mellitus, and Graves' disease. In view of the prolactin immunomodulatory
      roles, studying prolactin levels in pemphigus as an autoimmune blistering disease
      may introduce new ways of understanding disease etiology and developing treatment
      strategies. OBJECTIVE: Our purpose was to determine the prolactin levels in
      patients with newly diagnosed pemphigus vulgaris and study its correlation with
      pemphigus disease area index. LIMITATION: Our study was limited by the lack of a
      control group. METHODS: In this cross-sectional study, prolactin and anti
      desmoglein 1 and 3 autoantibodies levels were measured in 50 patients with newly
      diagnosed pemphigus vulgaris in Razi Dermatology Hospital. Pemphigus severity and
      extent was estimated using the Pemphigus Disease Area Index. RESULTS: Of the 50
      patients, 18 were male and 32 were female with a mean age of 41.56 +/- 13.66
      years. Mean prolactin (PRL) level was 15.60 +/- 11.72 ng/ml (10.68 in males and
      18.37 in females). Mean anti-desmoglein 1 and 3 autoantibodies were 135.8 +/-
      119.8 and 245.8 +/- 157.4 U/ml, respectively. Eleven out of 50 patients had a
      higher than normal prolactin range. No relation was found between prolactin level
      and disease activity (p = .982). Also, correlation studies show no relation
      between prolactin and anti-desmoglein 1 and 3 autoantibodies levels
      (respectively, p = .771 and .738). In comparing the extent of the disease between
      the two groups with normal and high prolactin, paired t-test showed no
      significance (p = .204). CONCLUSION: In our study, 22% of patients had
      hyperprolactinemia, which was greater among females. The highest PRL level was
      detected in mucocutaneous group. Although serum PRL levels were higher in
      patients with a greater Pemphigus Disease Area Index, it did not reach
      statistical significance.

PMID- 28492007
TI  - Colchicine may assist in reducing granulation tissue in junctional epidermolysis
      bullosa.
AB  - Epidermolysis bullosa (EB) is a rare, inherited blistering genodermatosis.
      Patients with junctional EB (JEB) due to LAMB3 mutations have widespread blisters
      and erosions of skin, mucosae, and nails, creating significant physical,
      emotional, and psychosocial burdens. Here we report the use of colchicine for
      ameliorating hypergranulating wounds in a 41-year-old female with JEB generalized
      intermediate. Her skin wounds and granulation tissue gradually exacerbated under
      silicone dressings such that she became profoundly anemic. Subsequently, she was
      commenced on colchicine 500 MUg daily on the basis that it may inhibit cell
      proliferation and be anti-inflammatory. After a 6-month trial of colchicine, she
      had an objective and subjective improvement in her validated EB Disease Activity
      and Scarring Index activity and damage scores and Quality Of Life in EB score
      with less skin erosions, granulation tissue, and erythema. In addition, her
      anemia resolved. She denied any gastrointestinal side effects. The exact
      mechanism of colchicine in assisting reduction of the blistering, erosions, and
      granulation in JEB is unclear, but the anti-inflammatory and antimitotic
      properties of colchicine may be partially responsible for this process.

PMID- 28492008
TI  - Physician-Industry Collaboration: Organizational Considerations for the Future of
      Innovation and Growth in Dermatology.
AB  - The U.S. medical environment continues to evolve with issues from Privacy to EMR,
      Insurance regulations, Physician Access and Healthcare Reform, and MACRA
      (Medicare Access and CHIP Reauthorization Act) on the discussion table. Not since
      the advent of Medicare and Medicaid in the mid 1960's, have we seen such
      widespread changes in the medical healthcare environment (Centers for Medicare
      and Medicaid Services). Physicians, industry, patients and consumers are affected
      by the changes. These four groups have historically worked as separate entities,
      but are now key stakeholders in the future of dermatology. As stakeholders
      collaborating in building a future together, the dermatologists/physicians will
      help to ensure and preserve the quality of patient care and best patient
      outcomes. In the Executive Forum, leaders from the Women's Dermatologic Society
      and Industry, explored five important areas: 1) A five-year outlook of
      Dermatology and Medicine; 2) Access of Industry to Dermatologists and Trainees;
      3) The New Practice Environment; 4) Doing Things Differently; and 5) Unmet
      Specialty Needs. The collaborative group explored solutions for our specialty and
      the patients we serve.

PMID- 28492009
TI  - Considerations on biologic agents in psoriasis with the new pregnancy lactation
      labeling rule.

PMID- 28492010
TI  - A case of Stevens-Johnson syndrome with gross hematuria.

PMID- 28492011
TI  - The good, the bad, and the ugly of medication coverage: Is altering a diagnosis
      to ensure medication coverage ethical?
AB  - Recently, a patient presented to the dermatology clinic suffering from disabling,
      recurrent palmoplantar vesicles and pustules. Biopsy demonstrated nondiagnostic
      histologic findings without unequivocal evidence for psoriasis. The localized
      rash was recalcitrant to a host of standard therapies. An anti-tumor necrosis
      factor biologic was considered, and experience suggested that this expensive
      medication would only be approved for coverage if a diagnosis was submitted for a
      Food and Drug Administration-approved indication as psoriasis. All health-care
      providers face similar dilemmas in caring for their own patients. To whom is the
      physician's primary responsibility when what is best for the patient may not
      align with the realities of our health-care system? Should a physician alter or
      exaggerate a medical diagnosis to obtain insurance coverage for a needed
      medication? What are the ethical implications of this action? If the physician's
      fiduciary duty to the patient had no limits, there would be multiple potential
      consequences including compromise of the health-care provider's integrity and
      relationships with patients, other providers, and third-party payers as well as
      the risk to an individual patient's health and creation of injustices within the
      health-care system.

PMID- 28492012
TI  - Gray Hair, Silver Linings, and the WDS.

PMID- 28492014
TI  - Woman, mother, and scientist: Aiming to fulfill a career in research while
      maintaining a "good-enough" work-life balance.

PMID- 28492013
TI  - Patient and practitioner satisfaction with tele-dermatology including Australia's
      indigenous population: A systematic review of the literature.
AB  - BACKGROUND: Australia's health disparity, combined with evolving technologies,
      has evoked increasing interest and funding in health services that could address
      inequities. One such emerging service is tele-medicine. OBJECTIVE: The purpose of
      this report is to discuss and evaluate the current literature regarding patient
      and practitioner satisfaction with tele-medicine, and more specifically tele
      dermatology. METHODS: We searched for literature relevant to tele-dermatology use
      among Australia's indigenous population. We synthesized the literature in our
      report and identified elements of tele-dermatology not yet researched. RESULTS:
      Most significantly, all available research is currently based on descriptive
      studies and there is no validated tool to assess the efficacy of tele
      dermatology. LIMITATIONS: No published research currently exists on the use of
      tele-dermatology among Australia's indigenous population. CONCLUSION: A review of
      the literature shows that tele-dermatology is considered a valuable service,
      particularly to patients living in rural areas who might not otherwise have
      access to specialist care.

PMID- 28492015
TI  - A dermatologist guide to immunogenicity.
AB  - Dermatologists should be aware that autoantibody formation may occur after the
      initiation of biologic therapy. This phenomenon has been referred to as
      immunogenicity and biologic fatigue. Because of this, patients may experience
      loss of clinical efficacy to a particular drug. To combat this phenomenon, low
      dose immunomodulators may be used in hopes of preventing autoantibodies. We
      review the current literature and provide a basic treatment algorithm for
      patients with moderate to severe psoriasis.

PMID- 28492016
TI  - Vaginal rejuvenation using energy-based devices.
AB  - Physiologic changes in a woman's life, such as childbirth, weight fluctuations,
      and hormonal changes due to aging and menopause, may alter the laxity of the
      vaginal canal, damage the pelvic floor, and devitalize the mucosal tone of the
      vaginal wall. These events often lead to the development of genitourinary
      conditions such as stress urinary incontinence; vaginal atrophy; dryness; and
      physiologic distress affecting a woman's quality of life, self-confidence, and
      sexuality. Various treatment modalities are currently available to manage these
      indications, varying from invasive vaginal surgery to more benign treatments like
      topical vaginal hormonal gels or hormone-replacement therapy. A new trend gaining
      momentum is the advent of energy-based devices for vaginal rejuvenation that
      apply thermal or nonthermal energy to the various layers of the vaginal tissue,
      stimulating collagen regeneration contracture of elastin fibers,
      neovascularization, and improved vaginal lubrication. This review aims to present
      the available technologies offering vaginal rejuvenation and the scientific
      evidence that underlines their safety and efficacy for this indication.

PMID- 28492017
TI  - Ecthyma gangrenosum secondary to methicillin-sensitive Staphylococcus aureus.
AB  - Ecthyma gangrenosum (EG) is a well-described skin manifestation of Pseudomonas
      aeruginosa septicemia in immunocompromised patients. However, it can be seen in
      association with other bacteria, viruses, and fungi. We report a case of a 54
      year-old African American female with metastatic gastric adenocarcinoma and
      recent chemotherapy and neutropenia who developed EG-like lesions due to
      methicillin-susceptible Staphylococcus aureus. We also review the literature to
      evaluate all reported cases of S aureus-associated EG and their clinical
      presentation, diagnosis, and treatment.

PMID- 28492018
TI  - Impact of leishmaniasis in women: a practical review with an update on my ISD
      supported initiative to combat leishmaniasis in Yemen (ELYP).
AB  - Stigma is synonymous with leishmaniasis, an endemic deadly flesh-eating disease
      in Yemen that affects predominantly poor rural women and children. Women with
      leishmaniasis often present late and experience not only physical deformities and
      the risk of death, but also the painful stigma of the disease and its
      consequences, a similar situation to that of leprosy decades ago. The
      International Society of Dermatology-sponsored community dermatology project
      Eradication of Leishmaniasis from Yemen Project has made a difference in the
      leishmaniasis situation in Yemen and addressed its magnitude. The program
      eradicated leishmaniasis from some areas, dealt with and improved its alarming
      prevalence among children and women who are the neglected and highest risk
      groups, and solved some issues associated with poor access to proper drugs.
      Medicine donation has enabled women with leishmaniasis to freely receive medicine
      they otherwise would not have been able to afford, reduced their mortality and
      morbidity, and minimized the extensive impact the socio-aesthetic stigma has on
      their lives. Our cause has attracted local and global attention to these
      problematic issues.

PMID- 28492019
TI  - Dr. Maureen Rogers, the first Australian pediatric dermatologist.

PMID- 28492021
TI  - A lesson learned about predatory journals and their difference from peer-reviewed
      open-access publishing.

PMID- 28492020
TI  - Helen Ollendorff-Curth: A dermatologist's lasting legacy.

PMID- 28492022
TI  - Medical publishing and the threat of predatory journals.

PMID- 28492023
TI  - Leprosy and women.
AB  - Leprosy has an impact on the physical, social, and psychological health of
      affected people. Women in developing countries seek health care late for any
      health-related issues. Leprosy, a disease known for its stigma, adds further to
      these facts. Also, close contact between women and family members, especially
      children, increases the chance of transmission to others and thereby increases
      the disease burden in the society. Hence, leprosy in women is an important issue
      for the affected patient, their family members, and society as a whole.

PMID- 28492024
TI  - Hair camouflage: A comprehensive review.
AB  - Hair is venerated, cherished, and desired in societies throughout the world. Both
      women and men express their individual identities through their hairstyles.
      Healthy hair contributes to successful social assimilation, employment, and
      overall quality of life. Therefore, hair loss can have detrimental effects on
      almost every aspect of a person's life. In this review, we discuss the myriad of
      options that aid in concealing and camouflaging hair loss to facilitate a
      healthier-appearing scalp. Camouflage options for patients who suffer from hair
      loss include full or partial wigs, hair extensions, concealing powders and
      sprays, surgical tattoos, and hair transplants. We describe these modalities in
      detail and discuss their respective advantages and disadvantages.

PMID- 28492025
TI  - Validation studies of outcome measures in pemphigus.
AB  - Pemphigus is a group of rare and potentially fatal autoimmune blistering diseases
      that are associated with auto-antibodies that target intercellular adhesion
      molecules. Incidence of pemphigus varies among populations, with the lowest
      incidence in Switzerland and Finland at 0.6-0.76 per million per year and the
      highest in Jewish communities at 16.1-32 per million per year. Pemphigus is
      associated with devastating morbidity and despite advancements in our
      understanding of the disease and a widening array of therapeutic options, no cure
      exists. The delay in the development of a cure may in part be attributed to the
      absence of a standardized and completely validated severity outcome measures to
      allow for high-quality multicenter control studies. Such a tool is necessary to
      define the best practice in clinical studies, allow for accurate comparisons
      between study results, justify drug use within the clinical setting, and reduce
      the cost burden that is associated with the use of ineffective therapies.
      Utilizing outcome measures that are not validated provides an opportunity to
      synthesize outcome measures with the intent to favor particular treatments and
      thus produce false conclusions. According to the COnsensus-based Standards for
      the selection of health Measurement INstruments (COSMIN) group, a validation of
      these measurement instruments requires investigating their responsiveness,
      reliability, and validity. More than 116 outcome measures exist to assess
      pemphigus severity, of which the Pemphigus Disease Area Index (PDAI), Autoimmune
      Bullous Skin Disorder Intensity Score (ABSIS), and Pemphigus Vulgaris Activity
      Score (PVAS) are the most comprehensively corroborated measures. With regard to
      validity and reliability, PDAI was unsurpassed by ABSIS and PVAS. Data indicate
      that ABSIS is more reliable than PVAS, but PVAS seems to have greater validity
      although the results are not consistent. PDAI, ABSIS, and PVAS have not yet had
      their responsiveness analyzed, which should be the next step to completely
      validate the outcome measures and conclusively determine which measure is
      superior.

PMID- 28492026
TI  - Acral self-healing collodion baby: A case series.
AB  - Collodion baby is a term used to describe a phenotype characterized by the
      presence of a tight, translucent membrane that covers the entire skin at birth.
      This membrane usually sheds around 10 to 14 days and reveals the underlying
      disease (mainly different types of Recessive Ichthyosis or other infrequent
      disorders). A rare variant of this phenotype is known as acral self-healing
      collodion baby whereby the patients are born with the typical membrane but
      limited to the hands and feet only, and after it sheds, the skin appears
      completely normal. We report five cases of this very rare subtype of collodion
      baby. All the patient cases that are presented involved both hands and feet. One
      of the patients also had the umbilicus embedded in a subtle collodion membrane.
      None of the patients had a family history of the same entity or any other type of
      ichthyosis. In all patients, the condition resolved spontaneously within a few
      weeks and no patients developed any other manifestation. Although no molecular
      analysis was performed, we contribute to the knowledge of the clinical features
      of this extremely uncommon and benign entity, since to the best of our knowledge
      there are only two previous reports available in literature.

PMID- 28492027
TI  - Tinea corporis in a wrestling team cheerleader.

PMID- 28492028
TI  - Professor Claudine Blanchet-Bardon: French dermatologist and leading authority on
      inherited ichthyoses.
AB  - This article recounts the early life and professional achievements through 2016
      of Professor Claudine Blanchet-Bardon, a French dermatologist who is known for
      her work in dermatogenetics, genetic counseling, and the care of patients with
      ichthyoses among other important work.

PMID- 28492029
TI  - Billing and up coding: What's a doctor-patient to do?

PMID- 28492030
TI  - Managing the dose escalation of biologics in an era of cost containment: the need
      for a rational strategy.
AB  - Although biologic medications have demonstrated great efficacy for the treatment
      of psoriasis, a subset of patients fails to respond and others lose response
      later in the course. In treating a patient who has failed to respond to biologic
      therapy, clinicians must decide between dose escalation, switching biologics, and
      adding or switching to a non-biologic systemic drug or phototherapy. Although
      dose escalation is perhaps the simplest strategy and generally well-tolerated, it
      confers a tremendous cost burden because doubling the dosage is likely to double
      the wholesale price. We call for the development of rational strategies for the
      pricing of dose escalation in order to minimize this phenomenon. We also call for
      increased transparency surrounding negotiated pricing to ensure that all patients
      have access to the most effective, affordable treatment options available.

PMID- 28492031
TI  - Retrospective evidence on outcomes and experiences of pregnancy and childbirth in
      epidermolysis bullosa in Australia and New Zealand.
AB  - BACKGROUND: Pregnancy in epidermolysis bullosa (EB) has not been comprehensively
      studied. OBJECTIVE: We aimed to develop a foundational database, which could
      provide peri-obstetric advice in EB. METHODS: Survey questionnaires were sent to
      obstetricians, unaffected mothers of EB babies, and mothers with EB. Results were
      analyzed using chi-square, Fisher exact, and t-tests. RESULTS: Out of 1346
      obstetricians surveyed, 195 responded, and only 14 had encountered EB. All
      recommended normal vaginal delivery (NVD), except for one elective Caesarean
      section (CS). We received responses from 75 unaffected mothers who had delivered
      EB babies. They had significantly more complications in their EB pregnancies
      compared to their non-EB pregnancies. A further 44 women with various types of EB
      who had given birth responded. Most delivered via NVD and had no significant
      increase in complications in both their EB and non-EB pregnancies. In both
      groups, there were no significant differences in blistering at birth in babies
      delivered via NVD and CS. CONCLUSION: In conclusion, most patients with EB who
      are capable of giving birth do not have an increased risk for pregnancy-related
      complications and NVD appears to be safe. Awareness of this data amongst
      obstetricians and dermatologists should lead to improved quality of care for
      mothers and babies affected with EB.

PMID- 28492032
TI  - Endocrine evaluation of hirsutism.
AB  - Hirsutism is defined as excessive terminal hair growth in a male pattern in
      females. It typically affects 5 to 10% of reproductive-age women. Excessive hair
      growth can often cause significant psychological and emotional distress. As a
      result, hirsutism is a common presenting complaint to healthcare professionals,
      including dermatologists, as women search for cosmetic and medical solutions to
      their problem. Hirsutism results from excess production of androgens, often from
      ovarian or adrenal sources. It is typically associated with a metabolic syndrome
      like polycystic ovarian syndrome (PCOS), but can be idiopathic or medication
      induced. This article provides an endocrine perspective for the evaluation and
      management of hirsutism.

PMID- 28492034
TI  - Mentoring and the U.K. Medical Women's Federation.

PMID- 28492033
TI  - Cutaneous melanoma in women.
AB  - BACKGROUND: Gender disparity in melanoma outcome is consistently observed,
      suggesting that gender is as an important prognostic factor. However, the source
      of this gender disparity in melanoma remains unclear. OBJECTIVE: This article
      reviews advances in our understanding of gender differences in melanoma and how
      such differences may contribute to outcomes. METHODS: A broad literature search
      was conducted using the PubMed database, with search terms such as 'gender
      differences in melanoma' and 'sex differences in melanoma.' Additional articles
      were identified from cited references. RESULTS: Herein, we address the gender
      linked physiologic differences in skin and melanoma. We discuss the influence of
      estrogen on a woman's risk for melanoma and melanoma outcomes with regard to
      pregnancy, oral contraceptives, hormone replacement therapy, and UV tanning.
      CONCLUSIONS: The published findings on gender disparities in melanoma have
      yielded many advances in our understanding of this disease. Biological,
      environmental, and behavioral factors may explain the observed gender difference
      in melanoma incidence and outcome. Further research will enable us to learn more
      about melanoma pathogenesis, with the goal of offering better treatments and
      preventative advice to our patients.

PMID- 28492035
TI  - The German experiment: health care without female or Jewish doctors.
AB  - Jewish and female doctors were not allowed to practice medicine in Germany during
      Hitler's rule from 1933 to 1945. Data about the consequences of this on the
      health service are difficult to come by, but what information can be gathered
      demonstrates a detrimental effect on the nation's health. These data, however,
      must be interpreted with consideration to the morbidity and mortality from
      violence, death camps, slave labor, and the privations of war. The article
      summarizes the history of German health care during this period and also compares
      Germany to other nations at that time.

PMID- 28492038
TI  - Dr. Wilma Fowler Bergfeld: A Woman of Substance, Role Model, and Founder of the
      Women's Dermatologic Society.

PMID- 28492037
TI  - The women behind the names: Dermatology eponyms named after women.

PMID- 28492039
TI  - Skin cancer concerns particular to women.
AB  - BACKGROUND: Skin cancer has reached epidemic proportions, with more new cases
      diagnosed annually than the combined incidence of cancers of the breast,
      prostate, lung, and colon. Estimates show 2 to 3 million new cases of non
      melanoma skin cancer (NMSC) every year, and, among women, it is the young
      (younger than 45 years) who are disproportionately affected. OBJECTIVE: This
      article aims to address questions and concerns pertinent to skin cancer in a
      woman-centric way. An updated landscape of causative factors, the latest
      detection/treatment methods, and ultimately the preventative measures available
      to them are described. METHODS: A broad literature search was conducted using the
      PubMed database with search terms focusing on female gender. Additional articles
      were identified from cited references. CONCLUSIONS: The published findings on
      causation of melanoma skin cancer and non-melanoma skin cancer in females are
      outlined, as well as current detection methods and treatment options.
      Furthermore, a variety of preventative measures specific to women that can reduce
      the chance of being diagnosed with skin cancer are discussed.

PMID- 28492036
TI  - Updates in the understanding and treatments of skin & hair disorders in women of
      color.
AB  - Skin of color comprises a diverse and expanding population of individuals. In
      particular, women of color represent an increasing subset of patients who
      frequently seek dermatologic care. Acne, melasma, and alopecia are among the most
      common skin disorders seen in this patient population. Understanding the
      differences in the basic science of skin and hair is imperative in addressing
      their unique needs. Despite the paucity of conclusive data on racial and ethnic
      differences in skin of color, certain biologic differences do exist, which affect
      the disease presentations of several cutaneous disorders in pigmented skin. While
      the overall pathogenesis and treatments for acne in women of color are similar to
      Caucasian men and women, individuals with darker skin types present more
      frequently with dyschromias from acne, which can be difficult to manage. Melasma
      is an acquired pigmentary disorder seen commonly in women with darker skin types
      and is strongly associated with ultraviolet (UV) radiation, genetic factors, and
      hormonal influences. Lastly, certain hair care practices and hairstyles are
      unique among women of African descent, which may contribute to specific types of
      hair loss seen in this population, such as traction alopecia, trichorrhexis
      nodosa and central centrifugal cicatricial alopecia (CCCA).

PMID- 28492040
TI  - What Ages Hair?

PMID- 28492041
TI  - A ten-year comparison of women authorship in U.S. dermatology literature, 1999
      vs. 2009.
AB  - Women are entering medicine at increasing rates, particularly in dermatology. In
      this study, we compared women's influence and status in academic dermatology with
      that of men by examining authorship roles in peer-reviewed dermatology
      literature. We examined the literature in 2009 and compared that to 10 years
      prior (1999). A total of 1399 articles were reviewed, 594 of which met study
      criteria and were included in statistical analysis. There was a marked increase
      in senior female authorship over a decade (22% vs. 38%, p < 0.001). Female first
      authorship increased as well (41% vs. 51%, p < 0.001). In contrast, changes in
      male senior and first authorship were not statistically significant. Federal
      funding for female senior authors increased over a decade (19% vs. 37%, p =
      0.05), and female senior authors in the 2009 cohort were more likely to hold a
      dual MD/PhD degree (0% vs. 11%, p = 0.04) or pure PhD degree (11% vs. 27%, p =
      0.04). Women are approaching parity with men in terms of authorship in the
      dermatology literature, and additional research training and attainment of
      federal funding have helped women publish as senior authors.

PMID- 28492042
TI  - Classifying discoid lupus erythematosus: background, gaps, and difficulties.
AB  - To inform our ongoing efforts to develop defining features to be incorporated
      into a novel set of classification criteria for discoid lupus erythematosus
      (DLE), we conducted a literature review using the Ovid MEDLINE database. A search
      was performed to identify studies reporting criteria used to distinguish DLE from
      other cutaneous lupus erythematosus subtypes. We examined which clinical,
      histopathologic, and serologic features have data to support their use as
      effective features in distinguishing DLE from other potential disease mimickers
      and cutaneous lupus subsets. Through our search, we were also able to identify
      gaps that exist in the literature which can inform future directions for research
      endeavors. We found that localization of lesions, characteristic features of
      damage, and the absence of high titer Ro/SSA antibody seem most effective in
      differentiating DLE from other cutaneous lupus erythematosus subtypes.
      Histopathologic features and class of immunoreactant deposition appear to be less
      helpful.

PMID- 28492043
TI  - Considerations on biologic agents in psoriasis with the new pregnancy lactation
      labeling rule.

PMID- 28492045
TI  - Hair camouflage: A comprehensive review.
AB  - Hair is venerated, cherished, and desired in societies throughout the world. Both
      women and men express their individual identities through their hairstyles.
      Healthy hair contributes to successful social assimilation, employment, and
      overall quality of life. Therefore, hair loss can have detrimental effects on
      almost every aspect of a person's life. In this review, we discuss the myriad of
      options that aid in concealing and camouflaging hair loss to facilitate a
      healthier-appearing scalp. Camouflage options for patients who suffer from hair
      loss include full or partial wigs, hair extensions, concealing powders and
      sprays, surgical tattoos, and hair transplants. We describe these modalities in
      detail and discuss their respective advantages and disadvantages.

PMID- 28492046
TI  - Introduction to women's health therapeutics in dermatology: Special edition of
      the International Journal of Women's Dermatology.

PMID- 28492044
TI  - Helen Ollendorff Curth: A dermatologist's lasting legacy.

PMID- 28492047
TI  - The ethical arguments in support of open access journals.

PMID- 28492048
TI  - A review of the safety of cosmetic procedures during pregnancy and lactation.
AB  - The safety of cosmetic procedures in patients who are pregnant and/or lactating
      is a complex clinical question surrounded by uncertainty. Our objective is to
      consolidate data on the safety of commonly requested cosmetic procedures during
      pregnancy and lactation after a systematic review of the current literature to
      guide evidence-based care in the future. A systematic search of the PubMed
      database was conducted for articles on cosmetic procedures during pregnancy and
      lactation. Due to a lack of controlled trials, case reports and series were
      considered. Minor procedures such as shave, punch, snipping, and electrocautery
      are considered safe. With respect to chemical peels, glycolic and lactic acid
      peels are deemed safe; however, trichloracetic and salicylic acid peels should be
      avoided or used with caution. Although safety data on botulinum toxin A is
      insufficient, the procedure may be safe because systemic absorption and placental
      transfer are negligible. Sclerotherapy can be safe during pregnancy but must be
      avoided during the first trimester and after week 36 of the pregnancy. Laser and
      light therapies have been considered generally safe for patients with
      granulomatous conditions and condylomata. Epilation should be limited to waxing,
      shaving, and topical treatments instead of permanent procedures. In patients who
      are lactating, most therapies discussed above are safe but fat transfer,
      sclerotherapy, and tumescent liposuction are not recommended. Better evidence is
      needed to make concrete recommendations on the safety of cosmetic therapy during
      pregnancy and lactation but preliminary evidence suggests excellent safety
      profiles for many commonly requested cosmetic procedures.

PMID- 28492049
TI  - A review of laser and light therapy in melasma.
AB  - Melasma is a dysregulation of the homeostatic mechanisms that control skin
      pigmentation and excess pigment is produced. Traditional treatment approaches
      with topical medications and chemical peels are commonly used but due to the
      refractory and recurrent nature of melasma, patients often seek alternative
      treatment strategies such as laser and light therapy. Several types of laser and
      light therapy have been studied in the treatment of melasma. Intense pulsed
      light, low fluence Q-switched lasers, and non-ablative fractionated lasers are
      the most common lasers and light treatments that are currently performed. They
      all appear effective but there is a high level of recurrence with time and some
      techniques are associated with an increased risk for postinflammatory hyper- or
      hypopigmentation. The number and frequency of treatments varies by device type
      but overall, Q-switched lasers require the greatest number of treatment
      applications to see a benefit. Vascular-specific lasers do not appear to be
      effective for the treatment of melasma. Ablative fractionated lasers should be
      used with caution because they have a very high risk for postinflammatory hypo-
      and hyperpigmentation. The use of nonablative fractionated laser treatments
      compared with other laser and light options may result in slightly longer
      remission intervals. Picosecond lasers, fractional radiofrequency, and laser
      assisted drug delivery are promising future approaches to treat melasma. The goal
      of this review is to summarize the efficacy and safety of the most commonly used
      laser and light therapies to treat melasma, briefly present future laser-based
      treatment options for patients with melasma, and provide recommendations for
      treatment on the basis of the reviewed information.

PMID- 28492050
TI  - Update on biologic safety for patients with psoriasis during pregnancy.
AB  - Biologic agents have become more common to treat patients with psoriasis, but
      concerns about their effect on pregnancy and lactation often preclude this
      treatment during these time periods. During the past decade, we have gained a
      much better understanding of the course of psoriasis during pregnancy and the
      safety of the use of biologic agents during pregnancy and lactation. Under
      certain circumstances, biologic agents can be considered appropriate treatment
      options for patients who are pregnant or lactating.

PMID- 28492051
TI  - Prognosis for women diagnosed with melanoma during, before, or after pregnancy:
      Weighing the evidence.
AB  - Approximately one third of women who are diagnosed with malignant melanoma are of
      childbearing age. Therefore, it is not surprising that some studies have found
      malignant melanoma to be one of the most common malignancies diagnosed in
      pregnant women. The impact of pregnancy-related hormonal changes on melanoma
      development and progression remains controversial. Women undergo immunologic
      changes during pregnancy that may decrease tumor surveillance. Additionally,
      hormone receptors are found on some melanomas. Unfortunately, many of the past
      and even recent studies that have been published and are reviewed herein did not
      uniformly use appropriate control groups, account for confounding covariates, or
      employ appropriate statistical analysis, which makes it difficult to rely on the
      conclusions they reach. However, a review of the better controlled and
      preponderant studies demonstrates that pregnancy-associated melanomas are not
      associated with a poorer prognosis.

PMID- 28492052
TI  - Dermatologic conditions in patients of color who are pregnant.
AB  - Certain dermatoses that present during pregnancy have a predilection for
      populations with skin of color (SOC). Additionally, certain systemic diseases
      such as systemic lupus erythematosus tend to be more aggressive during pregnancy
      and confer worse prognoses in women with SOC. The purpose of this review is to
      highlight the unique implications of selected diseases during pregnancy as it
      relates to SOC. Dermatologists should be vigilant for the unique clinical
      variations of dermatological conditions in patients of color who are pregnant to
      ensure correct diagnoses and optimize treatment outcomes.

PMID- 28492053
TI  - Association of ethnicity, Fitzpatrick skin type, and hirsutism: A retrospective
      cross-sectional study of women with polycystic ovarian syndrome.
AB  - BACKGROUND: The complex interplay between ethnicity, Fitzpatrick skin type (FST),
      and hirsutism in patients with polycystic ovarian syndrome (PCOS) is poorly
      understood. OBJECTIVE: In this cross-sectional, retrospective analysis, we
      examined the prevalence, severity, and distribution of hirsutism with clinician
      rated site-specific and total modified Ferriman-Gallwey (mFG) visual scoring in a
      diverse cohort of American patients with PCOS. METHODS: Independent analyses were
      conducted on the basis of patient-reported FST ratings and ethnicity. RESULTS: In
      this PCOS cohort, a correlation was found between hirsutism and ethnicity and the
      highest prevalence of hirsutism and total mFG scores was observed in Hispanic,
      Middle Eastern, African American, and South Asian patients. A positive
      correlation between hirsutism and FST was also observed with an increasing
      prevalence of hirsutism in the group of patients with higher FSTs. Significant
      trends in the anatomic distribution of hirsutism were observed between ethnic
      groups as well. A higher facial mFG score was found in African American patients
      but higher mFG scores in the truncal and extremity regions were observed in
      Middle Eastern patients. Truncal hirsutism was also associated with higher FSTs.
      CONCLUSIONS: Ethnicity and FST may be important variables in both the
      quantitative and qualitative presentations of hirsutism in women with PCOS and
      should be considered in the diagnostic evaluation of any patient who is suspected
      of having the condition. Previously published studies that examined ethnicity,
      FST, and hirsutism in homogeneous cohorts limited comparison and generalizability
      but the strength of this study lies in its detailed analysis within a single
      large and diverse PCOS cohort. Validated studies are needed to determine whether
      clinical criteria for hirsutism should be adjusted for ethnicity and FST in the
      PCOS population and particularly within diverse cohorts and patients of mixed
      ancestry.

PMID- 28492054
TI  - A Review of hormone-based therapies to treat adult acne vulgaris in women.
AB  - Hormone-based therapies including combined oral contraceptive medications and
      spironolactone are considered effective therapies to treat adult acne in women.
      Our objective is to provide a concise and comprehensive overview of the types of
      hormonal therapy that are available to treat acne and comment on their efficacy
      and safety profiles for clinical practice. A systematic search using the PubMed
      Database was conducted to yield 36 relevant studies for inclusion in the review
      and several conclusions were drawn from the literature. Treatment with oral
      contraceptive pills leads to significant reductions in lesion counts across all
      lesion types compared with placebo. There were no consistent differences in
      efficacy between the different combined oral contraceptive formulations. In terms
      of risk, oral contraceptive pill users had three-times increased odds of venous
      thromboembolism versus non-users according to a recent meta-analysis (95%
      confidence interval 2.46-2.59). Data on oral contraceptive pill use and breast
      cancer risk are conflicting but individual patient risk factors and histories
      should be discussed and considered when prescribing these medications. However,
      use of these medications does confer measurable protection from endometrial and
      ovarian cancer. Spironolactone was also shown to be an effective alternative
      treatment with good tolerability. Combined oral contraceptive medications and
      spironolactone as adjuvant and monotherapies are safe and effective to treat
      women with adult acne. However, appropriate clinical examinations, screening, and
      individual risk assessments particularly for venous thromboembolism risk must be
      conducted prior to initiating therapy.

PMID- 28492055
TI  - Hormonal therapy in female pattern hair loss.

PMID- 28492057
TI  - Dermatologic care of the transgender patient.
AB  - Given the complexities of the transitioning process, transgender individuals may
      face unique dermatologic needs in addition to routine care. Exogenous hormones
      affect hair and sebum production, gender-confirming surgeries often require
      dermatologic pre- and postoperative interventions, and postoperative anatomy may
      show unique presentations of routine skin conditions. Aesthetic techniques that
      are often used for rejuvenation may have a role in facial feminization and
      masculinization and unfortunately are too frequently performed by nonmedical
      personnel with negative consequences. Ultimately, physicians should strive to
      make their office a more accommodating environment for transgender individuals.

PMID- 28492056
TI  - Lichenoid vulvar disease: A review.
AB  - Vulvar dermatoses are common, potentially debilitating conditions that can be
      seen by a variety of medical specialists. Lichenoid vulvar diseases, namely
      lichen sclerosus (LS), lichen planus (LP), and lichen simplex chronicus (LSC),
      can all negatively impact patients' quality of life and LS and LP also have an
      association with squamous cell carcinoma. It is essential that dermatologists are
      familiar with the unique features of each of these conditions to ensure the
      appropriate management and follow up. Herein, we provide an update on the
      epidemiology, clinical presentation, histopathology, and treatment of patients
      with vulvar LS, LP, and LSC.

PMID- 28492058
TI  - Sexism in medicine, circa 2016-2017.

PMID- 28492059
TI  - Severity of memory impairment in the elderly: Association with health care
      resource use and functional limitations in the United States.
AB  - INTRODUCTION: Dementia is a prevalent condition in older adults associated with
      decline in cognitive and functional abilities and substantial burden. This study
      assessed the prevalence and impact of subjective memory impairment in the United
      States. METHODS: The 2011 to 2014 National Health and Nutrition Examination
      Survey, a population-based, nationally representative survey, was analyzed. Data
      included medical examinations, self-reported cognitive and functional
      limitations, and health care utilization over 1 year. Participants were aged >=65
      years and completed both interview and medical examination components.
      Descriptive analyses of patient characteristics were performed, and complex
      survey regression models were used to test associations. RESULTS: Of 2431 survey
      participants included, 53.1% had no memory impairment, 40.1% had early-stage
      memory impairment, and 6.6% had late-stage memory impairment. In adjusted
      analyses, late-stage versus no impairment was associated with more functional
      limitations (odds ratio [OR] = 7.26, P < .001), greater health care utilization
      (OR = 2.46, P < .001), and higher likelihood of seeing a mental health specialist
      (OR = 3.06, P = .001). DISCUSSION: Consistent with previous research, individuals
      with late-stage memory impairment had significantly greater functional
      limitations and higher health care utilization versus individuals with early
      stage or no memory impairment.

PMID- 28492060
TI  - Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in
      Rats.
AB  - A Target Animal Safety protocol was used to examine adverse events in male and
      female Fischer F344/NTac rats treated with increasing doses of a subcutaneous
      implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg
      afforded clinically significant blood levels of drug for 3 days. Chemistry,
      hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of
      the drug-lipid suspension were within normal limits. Histopathology findings were
      unremarkable. The skin and underlying tissue surrounding the drug injection were
      unremarkable. Approximately 25% of a cohort of rats given the excess doses of
      1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of
      intermittent and limited excess grooming and self-gnawing. These results confirm
      the safety of cholesterol-triglyceride carrier systems for subcutaneous drug
      delivery of buprenorphine in laboratory animals and further demonstrate the
      utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug
      therapy.

PMID- 28492061
TI  - Viability of Airborne Tumor Cells during Excision by Ultrasonic Device.
AB  - Background. Laparoscopic surgery has become more widely used, but peritoneal
      dissemination and port-site metastasis have been reported to occur in these
      surgeries. One reason for these problems is the ultrasonically activated scalpel
      (UAS) used for laparoscopic surgery. This study aimed to investigate the
      viability of airborne cells released during cancer dissection using a UAS.
      Methods. Flank tumors measuring about 2 cm were induced in male NOD-Cg
      Rag1tm1MomIL2rgtm1wjl/SzJ mice by subcutaneous injection of 1 * 106 HepG2 cells.
      Dissection was performed with UAS (in high or low power modes) and PowerStar
      bipolar scissors. The mist of released tissue was collected in cell culture
      medium. The viability of the cellular material was assessed with trypan blue
      exclusion cell counting, counting after immunofluorescence staining, and flow
      cytometric analysis. Results. Large quantities of cellular debris were trapped in
      the tissue dispersed by both devices. In all experiments, there were
      significantly more viable cells produced by the UAS in high power mode. By using
      suction at the excision site, the number of viable cancer cells was reduced.
      Conclusions. This study demonstrates that viable cancer cells can be released
      into the nearby environment during tumor ablation with a UAS.

PMID- 28492062
TI  - Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node
      Biopsy in Breast Cancer Patients: A Single Institution Experience.
AB  - Background. Most institutions require a patient undergoing sentinel lymph node
      biopsy to go through nuclear medicine prior to surgery to be injected with
      radioisotope. This study describes the long-term results using intraoperative
      injection of radioisotope. Methods. Since late 2002, all patients undergoing a
      sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent
      intraoperative injection of technetium-99m sulfur colloid. Endpoints included
      number of sentinel and nonsentinel lymph nodes obtained and number of positive
      sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node
      was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an
      identification rate of 99.8%. The median number of sentinel nodes found was 2 and
      the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel
      node was positive for metastatic carcinoma. Of the patients with a positive
      sentinel lymph node who underwent axillary dissection, there were 242 cases
      (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of
      intraoperative injection included increased comfort for the patient and
      simplification of scheduling. There were no radiation related complications.
      Conclusion. Intraoperative injection of technetium-99m sulfur colloid is
      convenient, effective, safe, and comfortable for the patient.

PMID- 28492063
TI  - Vaccination with Killed but Metabolically Active E. coli Over-expressing
      Hemagglutinin Elicits Neutralizing Antibodies to H1N1 Swine Origin Influenza A
      Virus.
AB  - There is a need for a fast and simple method for vaccine production to keep up
      with the pace of a rapidly spreading virus in the early phases of the influenza
      pandemic. The use of whole viruses produced in chicken eggs or recombinant
      antigens purified from various expression systems has presented considerable
      challenges, especially with lengthy processing times. Here, we use the killed but
      metabolically active (KBMA) Escherichia coli (E. coli) to harbor the
      hemagglutinin (HA) of swine origin influenza A (H1N1) virus (S-OIV) San
      Diego/01/09 (SD/H1N1-S-OIV). Intranasal vaccination of mice with KBMA E. coli
      SD/H1N1-S-OIV HA without adding exogenous adjuvants provoked detectable
      neutralizing antibodies against the virus-induced hemagglutination within three
      weeks. Boosting vaccination enhanced the titers of neutralizing antibodies, which
      can decrease viral infectivity in Madin-Darby canine kidney (MDCK) cells. The
      antibodies were found to specifically neutralize the SD/H1N1-S-OIV-, but not
      seasonal influenza viruses (H1N1 and H3N2), -induced hemagglutination. The use of
      KBMA E. coli as an egg-free system to produce anti-influenza vaccines makes
      unnecessary the rigorous purification of an antigen prior to immunization,
      providing an alternative modality to combat influenza virus in future outbreaks.

PMID- 28492064
TI  - Biophysical characterization and modeling of human Ecdysoneless (ECD) protein
      supports a scaffolding function.
AB  - The human homolog of Drosophila ecdysoneless protein (ECD) is a p53 binding
      protein that stabilizes and enhances p53 functions. Homozygous deletion of mouse
      Ecd is early embryonic lethal and Ecd deletion delays G1-S cell cycle
      progression. Importantly, ECD directly interacts with the Rb tumor suppressor and
      competes with the E2F transcription factor for binding to Rb. Further studies
      demonstrated ECD is overexpressed in breast and pancreatic cancers and its
      overexpression correlates with poor patient survival. ECD overexpression together
      with Ras induces cellular transformation through upregulation of autophagy.
      Recently we demonstrated that CK2 mediated phosphorylation of ECD and interaction
      with R2TP complex are important for its cell cycle regulatory function.
      Considering that ECD is a component of multiprotein complexes and its crystal
      structure is unknown, we characterized ECD structure by circular dichroism
      measurements and sequence analysis software. These analyses suggest that the
      majority of ECD is composed of alpha-helices. Furthermore, small angle X-ray
      scattering (SAXS) analysis showed that deletion fragments, ECD(1-432) and ECD(1
      534), are both well-folded and reveals that the first 400 residues are globular
      and the next 100 residues are in an extended cylindrical structure. Taking all
      these results together, we speculate that ECD acts like a structural hub or
      scaffolding protein in its association with its protein partners. In the future,
      the hypothetical model presented here for ECD will need to be tested
      experimentally.

PMID- 28492065
TI  - Revisiting olfactory receptors as putative drivers of cancer.
AB  - Background: Olfactory receptors (ORs) recognize odorant molecules and activate a
      signal transduction pathway that ultimately leads to the perception of smell.
      This process also modulates the apoptotic cycle of olfactory sensory neurons in
      an olfactory receptor-specific manner. Recent reports indicate that some
      olfactory receptors are expressed in tissues other than the olfactory epithelium
      suggesting that they may have pleiotropic roles. Methods: We investigated the
      expression of 301 olfactory receptor genes in a comprehensive panel of 968 cancer
      cell lines. Results: Forty-nine per cent of cell lines show expression of at
      least one olfactory receptor gene. Some receptors display a broad pattern of
      expression across tumour types, while others were expressed in cell lines from a
      particular tissue. Additionally, most of the cancer cell lines expressing
      olfactory receptors express the effectors necessary for OR-mediated signal
      transduction. Remarkably, among cancer cell lines, OR2C3 is exclusively expressed
      in melanoma lines. We also confirmed the expression of OR2C3 in human melanomas,
      but not in normal melanocytes. Conclusions: The pattern of OR2C3 expression is
      suggestive of a functional role in the development and/or progression of
      melanoma. Some olfactory receptors may contribute to tumorigenesis.

PMID- 28492067
TI  - Social Structure and Depression in TrevorSpace.
AB  - We discover patterns related to depression in the social graph of an online
      community of approximately 20,000 lesbian, gay, and bisexual, transgender, and
      questioning youth. With survey data on fewer than two hundred community members
      and the network graph of the entire community (which is completely anonymous
      except for the survey responses), we detected statistically significant
      correlations between a number of graph properties and those TrevorSpace users
      showing a higher likelihood of depression, according to the Patient Healthcare
      Questionnaire-9, a standard instrument for estimating depression. Our results
      suggest that those who are less depressed are more deeply integrated into the
      social fabric of TrevorSpace than those who are more depressed. Our techniques
      may apply to other hard-to-reach online communities, like gay men on Facebook,
      where obtaining detailed information about individuals is difficult or expensive,
      but obtaining the social graph is not.

PMID- 28492068
TI  - Survival and Neurodevelopment of Periviable Infants.

PMID- 28492069
TI  - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PMID- 28492070
TI  - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PMID- 28492066
TI  - Progression inference for somatic mutations in cancer.
AB  - Computational methods were employed to determine progression inference of genomic
      alterations in commonly occurring cancers. Using cross-sectional TCGA data, we
      computed evolutionary trajectories involving selectivity relationships among
      pairs of gene-specific genomic alterations such as somatic mutations, deletions,
      amplifications, downregulation, and upregulation among the top 20 driver genes
      associated with each cancer. Results indicate that the majority of hierarchies
      involved TP53, PIK3CA, ERBB2, APC, KRAS, EGFR, IDH1, VHL, etc. Research into the
      order and accumulation of genomic alterations among cancer driver genes will ever
      increase as the costs of nextgen sequencing subside, and personalized/precision
      medicine incorporates whole-genome scans into the diagnosis and treatment of
      cancer.

PMID- 28492071
TI  - Left Ventricular Assist Devices for Advanced Heart Failure.

PMID- 28492072
TI  - Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use.

PMID- 28492073
TI  - Polyvalent and Thermosensitive DNA Nanoensembles for Cancer Cell Detection and
      Manipulation.
AB  - Development of smart DNA nanostructures is of great value in cancer studies.
      Here, by integrating rolling circle amplification (RCA) into split aptamer
      design, a novel strategy of polyvalent and thermosensitive DNA nanoensembles was
      first proposed for cancer cell detection and manipulation. In this strategy, a
      long nanosolo ssDNA with repeated Split-b and Poly T regions was generated
      through RCA. Split-b supplied polyvalent binding sites while Poly T supported
      signal output by hybridizing with fluorophore-labeled poly A. After addition of
      Split-a, nanoensembles formed on the cell surface due to target-induced assembly
      of Split-a/Split-b from the free state to the recognition structure, and on the
      basis of the thermosensitivity of split aptamer, nanoensembles were controlled
      reversibly by changing temperatures. As proof of concept, split ZY11 against SMMC
      7721 cancer was used to construct nanoensembles. Compared with monovalent split
      aptamer, nanoensembles were demonstrated to have a much stronger interaction with
      target cells, thus realizing an ~2.8-time increase in signal-to-background ratio
      (SBR). Moreover, nanoensembles extended the tolerance range of target binding
      from 4  degrees C to room temperature and speeded recognition thus achieving
      almost 50% binding in 1 min. Then, nanoensembles were successfully applied to
      detect 7721 cells in serum and mixed cell samples. By utilizing microplate well
      surface as the model, temperature-controlled catch/release of target cells was
      also realized with nanoensembles, even under unfriendly conditions for monovalent
      split aptamer. The RCA-mediated aptameric nanoensembles strategy not only solved
      the problem of split aptamer in inefficient binding but also paved a brand new
      way for developing polyvalent and intelligent nanomaterials.

PMID- 28492074
TI  - Inhibiting Firefly Bioluminescence by Chalcones.
AB  - Chalcone refers to an aromatic ketone and an enone that constitutes the central
      core for various important biological compounds in drug discovery. Moreover, the
      firefly luciferase (Fluc) as the bioluminescent reporter has been widely used in
      life science research and high-throughput screening (HTS). However, Fluc might
      suffer from direct inhibition by HTS compounds resulting in the occurrence of
      "false positives." In the current research, we discovered a series of chalcone
      compounds as Fluc inhibitors with favorable potency both in vitro and in vivo.
      Moreover, our compound 3i showed remarkable systemic inhibition in transgenic
      mice. Both enzymatic kinetics study and cocrystal structure demonstrated that
      compound 3i is competitive for substrate aminoluciferin, while noncompetitive for
      ATP. Besides, compound 3i exhibited excellent selectivity as a promising
      quenching agent in a simulated dual-luciferase reporter assay. We believed that
      our research would contribute to improving scientists' awareness of the Fluc
      inhibitors, pay attention to the bias results, and even expand the utilization of
      bioluminescence in life science research.

PMID- 28492075
TI  - Energy Transfer Highway in Nd3+-Sensitized Nanoparticles for Efficient near
      Infrared Bioimaging.
AB  - Despite the large absorption cross-section of Nd3+ dopant as a sensitizer in
      lanthanide doped luminescence system, the strong cross-relaxation effect of it
      impedes the promotion of doping concentration and thus reduces the utilization of
      excitation light. In this work, we introduce a highly efficient acceptor, Yb3+
      ion, which can quickly receive energy from Nd3+ ions, to construct an energy
      transfer highway for the enhancement of near-infrared emission. By using the
      energy transfer highway, the doping amount of Nd3+ ions in our NaYF4:Yb,Nd@CaF2
      core/shell nanoparticles (CSNPs) can be markedly elevated to 60%. The quantum
      yield of CSNPs was determined to be 20.7%, which provides strong near-infrared
      luminescence for further bioimaging application. Remarkably, deep tissue
      penetration depth (~10 mm) in in vitro imaging and high spatial resolution of
      blood vessel (~0.19 mm) in in vivo imaging were detected clearly with weak
      autofluorescence, demonstrating that probes can be used as excellent NIR
      biosensors.

PMID- 28492076
TI  - Total Synthesis of gamma-Indomycinone and Kidamycinone by Means of Two
      Regioselective Diels-Alder Reactions.
AB  - An efficient access for the synthesis of pluramycinones is described. Total
      syntheses of racemic gamma-indomycinone and kidamycinone were achieved by means
      of two Diels-Alder reactions. A first Diels-Alder condensation followed by a
      Stille cross-coupling is used for the elaboration of the desired substituted
      dienes which will be involved in the second pericyclic reaction with juglone to
      construct the tetracyclic core of pluramycinones.

PMID- 28492077
TI  - Anomalously Rapid Tunneling: Charge Transport across Self-Assembled Monolayers of
      Oligo(ethylene glycol).
AB  - This paper describes charge transport by tunneling across self-assembled
      monolayers (SAMs) of thiol-terminated derivatives of oligo(ethylene glycol)
      (HS(CH2CH2O)nCH3; HS(EG)nCH3); these SAMs are positioned between gold bottom
      electrodes and Ga2O3/EGaIn top electrodes. Comparison of the attenuation factor
      (beta of the simplified Simmons equation) across these SAMs with the
      corresponding value obtained with length-matched SAMs of oligophenyls (HS(Ph)nH)
      and n-alkanethiols (HS(CH2)nH) demonstrates that SAMs of oligo(ethylene glycol)
      have values of beta (beta(EG)n = 0.29 +/- 0.02 natom-1 and beta = 0.24 +/- 0.01 A
      1) indistinguishable from values for SAMs of oligophenyls (beta(Ph)n = 0.28 +/-
      0.03 A-1), and significantly lower than those of SAMs of n-alkanethiolates
      (beta(CH2)n = 0.94 +/- 0.02 natom-1 and 0.77 +/- 0.03 A-1). There are two
      possible origins for this low value of beta. The more probable involves hole
      tunneling by superexchange, which rationalizes the weak dependence of the rate of
      charge transport on the length of the molecules of HS(EG)nCH3 using interactions
      among the high-energy, occupied orbitals associated with the lone-pair electrons
      on oxygen. Based on this mechanism, SAMs of oligo(ethylene glycol)s are good
      conductors (by hole tunneling) but good insulators (by electron and/or hole drift
      conduction). This observation suggests SAMs derived from these or electronically
      similar molecules are a new class of electronic materials. A second but less
      probable mechanism for this unexpectedly low value of beta for SAMs of S(EG)nCH3
      rests on the possibility of disorder in the SAM and a systematic discrepancy
      between different estimates of the thickness of these SAMs.

PMID- 28492078
TI  - General Strategy for Controlled Synthesis of NixPy/Carbon and Its Evaluation as a
      Counter Electrode Material in Dye-Sensitized Solar Cells.
AB  - Hydrothermal treatment of nickel acetate and phosphoric acid aqueous solution
      followed with a carbothermal reduction assisted phosphorization process using
      sucrose as the carbon source for the controlled synthesis of NixPy/C was
      successfully realized for the first time. The critical synthesis factors,
      including reduction temperature, phosphorus/nickel ratio, pH, and sucrose amount
      were systematically investigated. Remarkably, the carbon serves as a reducer and
      plays a determinative role in the transformation of Ni2P2O7 into Ni2P/C. The
      synthesis strategy is divided into four distinguishable stages: (1) hydrothermal
      preparation of Ni3(PO4)2.8H2O precursor for stabilizing P sources; (2)
      dimerization of Ni3(PO4)2.8H2O into more thermal stable Ni2P2O7 amorphous phase
      along with the generation of NiO; (3) carbothermal reduction and phosphidation of
      NiO into NixPy (0 <= y/x <= 0.5); and (4) further phosphidation of mixed-phase
      NixPy and carbothermal reduction of Ni2P2O7 into single-phase Ni2P. The resultant
      Ni2P, the highly active phase in electrocatalysis, was applied as counter
      electrode in a dye-sensitized solar cell (DSSC). The DSSC based on Ni2P with 10.4
      wt.% carbon delivers a power conversion efficiency of 9.57%, superior to that of
      state-of-the-art Pt-based cell (8.12%). The abundant Nidelta+ and Pdelta- active
      sites and the metal-like conductivity account for its outstanding catalytic
      performance.

PMID- 28492079
TI  - Chemical Vapor Deposition Synthesis and Optical Properties of Nb2O5 Thin Films
      with Hybrid Functional Theoretical Insight into the Band Structure and Band Gaps.
AB  - Nb2O5 is an important material able to exist in many polymorphs with unique
      optical properties and morphologies that are dependent on the synthetic route.
      Here we report a novel ambient-pressure chemical vapor deposition route to Nb2O5
      via aerosol-assisted chemical vapor deposition. The amorphous as-deposited films
      were annealed in air to obtain the the three most stable crystal structures:
      orthorhombic, tetragonal, and monoclinic. The films were thoroughly characterized
      for their material properties, and an in-depth study into the optical properties
      was carried out using state-of-the-art hybrid functional theory that allowed more
      insight into the optical properties of the materials.

PMID- 28492080
TI  - Artemisinin-Luminol Chemiluminescence for Forensic Bloodstain Detection Using a
      Smart Phone as a Detector.
AB  - Forensic luminol chemiluminescence test is one of the most sensitive and popular
      methods for the determination of latent bloodstains. It mainly uses hydrogen
      peroxide or sodium perborate as coreactants. The easy decomposition of hydrogen
      peroxide and sodium perborate in the presence of many ions significantly affects
      the selectivity. Artemisinin is a natural peroxide that is quite stable in the
      presence of common ions. In the present study, artemisinin has been exploited for
      the forensic bloodstain chemiluminescence detection for the first time. Using
      smart phone as cost-effective portable detector, the visual detection of
      bloodstains has been achieved with a dilution factor of blood up to 100 000.
      Moreover, this system shows excellent selectivity against many common species. It
      can well differentiate bloodstains from other stains, such as coffee, brown
      sugar, and black tea. Both favorable sensitivity and selectivity makes the
      present method promising in forensic detection.

PMID- 28492081
TI  - Junction Propagation in Organometal Halide Perovskite-Polymer Composite Thin
      Films.
AB  - With the emergence of organometal halide perovskite semiconductors, it has been
      discovered that a p-i-n junction can be formed in situ due to the migration of
      ionic species in the perovskite when a bias is applied. In this work, we
      investigated the junction formation dynamics in methylammonium lead tribromide
      (MAPbBr3)/polymer composite thin films. It was concluded that the p- and n- doped
      regions propagated into the intrinsic region with an increasing bias, leading to
      a reduced intrinsic perovskite layer thickness and the formation of an effective
      light-emitting junction regardless of perovskite layer thicknesses (300 nm to 30
      MUm). The junction propagation also played a major role in deteriorating the LED
      operation lifetime. Stable perovskite LEDs can be achieved by restricting the
      junction propagation after its formation.

PMID- 28492082
TI  - Metabolomics Approach in the Investigation of Metabolic Changes in Obese Men
      after 24 Weeks of Combined Training.
AB  - Obesity is associated with comorbidities related to metabolic disorders due to
      excess of adipose tissue. Physical exercise has a major role in the prevention of
      obesity. Combined training (CT), in particular, has been shown to improve markers
      of health. In this study, we used 1H NMR-based metabolomics to investigate
      changes in the metabolism of obese men after 24 weeks of CT. Twenty-two obese
      (body mass index 31 +/- 1.4 kg/m2), middle-aged men (48.2 +/- 6.1 years) were
      randomly assigned to a control group (CG, n = 11) or CT group (n = 11). The CT
      was performed three times a week (resistance and aerobic training) for 24 weeks.
      Blood samples were collected before and after experimental period. There was an
      improvement in body composition and physical fitness indices after CT training.
      Multivariate PCA and PLS-DA models showed a distinct separation between groups.
      Twenty metabolites with importance for projection (VIP) >1.0 were identified, and
      four were classified as best discriminators (tyrosine, 2-oxoisocaproate,
      histidine, pyruvate). Some metabolites were correlated with strength, VO2 peak,
      fat and lean body mass, waist circumference, and insulin. In conclusion, 24 weeks
      of CT was effective for functional improvements and metabolic changes in obese
      middle-aged men.

PMID- 28492083
TI  - B(C6F5)3-Catalyzed Michael Reactions: Aromatic C-H as Nucleophiles.
AB  - The Michael reaction is a widely used reaction for the C-C coupling of electron
      poor olefins and C(sp3)-H pronucleophiles. Herein we report the Michael reaction
      between alkenes and aromatic as well as heteroaromatic compounds as aromatic
      C(sp2)-H nucleophiles under mild conditions. The reaction is catalyzed by readily
      available Lewis acidic B(C6F5)3 and proceeds with high regioselectivity for a
      wide substrate scope.

PMID- 28492084
TI  - Prehospital triage of patients suffering severe dyspnoea using N-terminal pro
      brain natriuretic peptide, the PreBNP trial: a randomised controlled clinical
      trial.
AB  - PURPOSE: The purpose of this study was to examine whether the addition of brain
      natriuretic peptide measurement to the routine diagnostic work-up by prehospital
      critical care team physicians improves triage in patients with severe dyspnoea.
      METHODS: Prehospital critical care team physicians randomly assigned patients
      older than 18 years with severe dyspnoea to routine diagnostic work-up or
      diagnostic work-up with incorporated point-of-care N-terminal pro-brain
      natriuretic peptide (NT-proBNP) measurement. The primary endpoint was the
      proportion of patients with dyspnoea of primary cardiac origin triaged directly
      to a department of cardiology. RESULTS: A total of 747 patients were randomly
      assigned and 711 patients consented to participate, 350 were randomly assigned to
      the NT-proBNP group and 361 to the routine work-up group. NT-proBNP was measured
      in 90% (315/350) of patients in the NT-proBNP group and in 19% (70/361) of
      patients in the routine work-up group. There was no difference in the proportion
      of patients with dyspnoea of primary cardiac origin triaged directly to a
      department of cardiology between the NT-proBNP group and the routine work-up
      group (75% vs. 69%, P=0.22) in the intention-to-treat analysis. Sensitivity
      analysis according to the de facto diagnostics performed showed results
      consistent with this. No differences in hospital length of stay, intensive care
      unit admission rates or mortality between the NT-proBNP group and the routine
      work-up group were observed. CONCLUSION: Routine supplementary point-of-care
      measurement of NT-proBNP in patients with severe dyspnoea did not improve triage
      of patients with dyspnoea primarily caused by heart disease. ClinicalTrials.gov
      identifier NCT02050282.

PMID- 28492085
TI  - Self-managing HIV/AIDS: cultural competence and health among women in Nairobi,
      Kenya.
AB  - Despite recent efforts to supply antiretroviral therapy, many in Africa are not
      receiving medication, instead relying on self-management in their attempts to
      remain healthy. In Kenya, the majority of those infected are women who are below
      the extreme poverty level. Building on research demonstrating a link between
      knowledge of HIV/AIDS management and the length of time HIV-positive women have
      lived in Nairobi, this article uses a cognitive anthropological approach that
      conceives of culture as shared models and explores the relationship between how
      well women know a cultural model of self-managing HIV/AIDS and health among women
      who are not receiving biomedical treatment. Outcomes include reported perceived
      stress, depressive symptoms, and recent illness episodes. Here, this association
      of competence in the shared cultural model and health among women living in
      extremely marginal economic conditions is explored from a biocultural perspective
      to better understand this relationship. Knowledge of the model is a significant
      predictor of better overall health even after controlling for age, education,
      income, marital status, internal locus of control, and how long women have known
      that they are HIV-positive. This article adds to the HIV/AIDS literature by
      quantitatively linking health to cultural knowledge among an HIV-positive
      population. It also contributes to the cultural consensus literature by
      demonstrating health benefits of cultural knowledge.

PMID- 28492086
TI  - Novel translational therapeutic strategy by sequencing primary liver cancer
      genomes.

PMID- 28492087
TI  - Sociodemographic characteristics associated with the use of effective and less
      effective contraceptive methods: findings from the Understanding Fertility
      Management in Contemporary Australia survey.
AB  - OBJECTIVE: Unintended pregnancy and abortion may, in part, result from suboptimal
      use of effective contraception. This study aimed to identify sociodemographic
      factors associated with the use of effective and less effective methods among
      women and men of reproductive age living in Australia. METHODS: In a cross
      sectional national survey, 1544 women and men aged 18-51 were identified as being
      at risk of pregnancy. Chi-square and logistic regression analyses were used to
      assess the sociodemographic factors related to contraceptive use. RESULTS: Most
      respondents (n = 1307, 84.7%) reported using a method of contraception. Use of
      any contraceptive was associated with being born in Australia (Odds Ratio [OR]
      1.89; 95% Confidence Interval [CI]1.186, 3.01; p = .008), having English as a
      first language (OR 1.81; 95% CI: 1.07, 3.04; p = .026), having private health
      insurance (OR 2.25; 95% CI 1.66, 3.04; p < .001), and not considering religion
      important to fertility choices (OR 0.43; 95%CI 0.31, 0.60; p < .001). A third
      used effective contraceptive methods (n = 534, 34.6%; permanent methods: 23.1%,
      and long-acting reversible contraception (LARC): 11.4%). Permanent methods were
      more likely to be used in rural areas (OR 0.62; 95%CI 0.46, 0.84; p = .002). Use
      of the least effective, short-term methods was reported by nearly half (condoms:
      25.6%, withdrawal: 12.5%, and fertility-awareness-based methods: 2.8%). Those who
      relied on withdrawal were more likely to live in a metropolitan area (OR 2.85;
      95% CI 1.95, 4.18; p < .001), and not have private health insurance (OR 0.52; 95%
      CI 0.38, 0.71; p < .001). CONCLUSIONS: Targeted promotion of the broad range of
      available contraceptives may raise awareness and uptake of more effective methods
      and improve reproductive autonomy in certain population groups.

PMID- 28492088
TI  - Donor selection for ex vivo-expanded natural killer cells as adoptive cancer
      immunotherapy.

PMID- 28492089
TI  - Does physical activity improve survival and mortality among patients with
      different types of cancer?

PMID- 28492090
TI  - Synthesis and structure-activity relationship of theasapogenol galactosides
      against Magnaporthe oryzae.
AB  - Camellia oleifera is expected to provide alternative aglycone to synthesize some
      saponins similar to that from Schima superba with inhibitory activity against
      Magnaporthe oryzae. Eight theasapogenol galactosides were synthesized via
      protection of adjacent hydroxyl groups by a benzylidene for regioselective
      glycosylation in the multi-hydroxyl sapogenin. Water soluble galactose chain
      connected far from liposoluble end was a key group in inhibiting the growth of M.
      oryzea unless theasapogenol was modified by two galactosyl groups or by one
      galactosyl group and one benzylidene group. The amphoteric characteristics of
      saponin such as saccharide group number, distance between bipolar groups play an
      important role in inhibiting mycelium growth of M. oryzae.

PMID- 28492091
TI  - The schizophrenia stigma and mass media: a search for news published by wide
      circulation media in Brazil.
AB  - Schizophrenia is the most common illness used today as a metaphor in the media
      and routinely appears associated with crime and violence with no medical or
      scientific rigor, reinforcing the stigma against this disorder. Evaluation of the
      presence of structural stigma in the Brazilian media by means of a survey of
      printed news and the Internet using the term schizophrenia and its correlates
      under three aspects: (a) medical and scientific uses, (b) assigning a diagnosis
      of schizophrenia to crime suspects with little or no medical or scientific rigor,
      and (c) the metaphorical use. The study was conducted in three stages: search for
      publications, classification of items found and analysis of the context in which
      they were published. The survey was conducted in two periods: 2008 and 2011, the
      first being restricted to the newspaper Folha de S. Paulo and the second extended
      to the homepage of the main Brazilian print media. We found 229 texts,
      distributed as follows: 89 (39%) records as science and health, with a tendency
      to impersonality; 62 (27%) records as crime and violence, in which the
      'diagnosis' of schizophrenia is given by lay people and 'supported' by an
      archeology of the life of the suspect which enlists all sorts of non-standard
      behavior; and 78 (34%) records of metaphorical use, always with a negative
      meaning. Most of the texts found (a) does not give voice to people with
      schizophrenia and their suffering, (b) trivializes the use of this psychiatric
      illness out of context to describe contradictory or of dubious character
      political and economic decisions, and

PMID- 28492092
TI  - Use of descriptive and experiential information in decision making by young and
      older adults.
AB  - Age differences involving decision by description versus decision by experience
      were examined using the same general task structure to facilitate comparisons
      across decision types. Experiment 1 compared younger (19-43 years) and older (65
      85 years) adults in four different experimental conditions involving a choice
      between a low-risk, low-return bet versus a high-risk, high-return bet.
      Experiment 2 compared young (18-27 years) to older (60-87 years) adults using
      similar experimental conditions, but with decisions involving a risky versus a
      certain option. Contrary to expectations, minimal differences were observed
      between ages in either study. Higher levels of ability and numeracy were
      associated with better performance and greater ability to benefit from
      experience, but the impact of these factors was not moderated by age. The results
      suggest that factors other than the simple distinction between decisions by
      description versus experience are necessary to characterize the nature of age
      effects in decision-making.

PMID- 28492094
TI  - Bronchial Mucoepidermoid Carcinoma With the Classic MAML2 Gene Rearrangement in a
      2-year-old Boy.
AB  - Pulmonary mucoepidermoid carcinoma (PMEC) is rare. To date, primary PMEC has not
      been reported in a child younger than 3 years of age. We report a case of a 2
      year-old boy who presented with 3 episodes of wheezing, cough, and fever over a
      period of 1 month. Radiologic findings were consistent with foreign body
      aspiration with consequent bronchial obstruction. Bronchoscopy was performed and
      attempts to retrieve the foreign body resulted in a biopsy of a fleshy lesion. By
      histology, the lesion was an epithelial neoplasm comprising cells arranged in a
      nested pattern. The neoplastic cells were round with round nuclei and
      amphophilic, vacuolated cytoplasm. Our diagnosis was low-grade salivary gland
      type carcinoma of the bronchus. The pneumonectomy specimen showed a well
      circumscribed, polypoid intrabronchial mass measuring 2.1 cm in greatest
      dimension. Histologic examination of the tumor showed an admixture of
      intermediate cells which were predominant, a small number of mucus cells and rare
      foci of squamous cells. The final diagnosis rendered was a low-grade
      mucoepidermoid carcinoma of the bronchus. Accurate diagnosis of PMEC can be
      challenging on limited biopsy material as seen in the case reported here. The use
      of molecular studies such as MAML2 gene rearrangement may facilitate diagnosis in
      difficult cases. Increased awareness of this entity and further molecular studies
      are needed for a better understanding of the pathogenesis of PMEC. To date, the
      reported age range for primary bronchial mucoepidermoid carcinoma is between 3
      years and 78 years. This case represents the youngest patient reported in the
      English literature.

PMID- 28492093
TI  - Higher prevalence of cerebral white matter hyperintensities in homozygous APOE-E4
      allele carriers aged 45-75: Results from the ALFA study.
AB  - Cerebral white matter hyperintensities are believed the consequence of small
      vessel disease and are associated with risk and progression of Alzheimer's
      disease. The E4 allele of the APOE gene is the major factor accountable for
      Alzheimer's disease heritability. However, the relationship between white matter
      hyperintensities and APOE genotype in healthy subjects remains controversial. We
      investigated the association between APOE-E4 and vascular risk factors with white
      matter hyperintensities, and explored their interactions, in a cohort of
      cognitively healthy adults (45-75 years). White matter hyperintensities were
      assessed with the Fazekas Scale from magnetic resonance images (575 participants:
      74 APOE-E4 homozygotes, 220 heterozygotes and 281 noncarriers) and classified
      into normal (Fazekas < 2) and pathological (>=2). Stepwise logistic regression
      was used to study the association between pathological Fazekas and APOE genotype
      after correcting for cardiovascular and sociodemographic factors. APOE-E4
      homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432;
      95% CI [1.297-9.082]; p = 0.013) of displaying pathological white matter
      hyperintensities. As expected, aging, hypertension and cardiovascular and
      dementia risk scales were also positively associated to pathological white matter
      hyperintensities, but these did not modulate the effect of APOE-E4/E4. In
      subjects at genetic risk of developing Alzheimer's disease, the control of
      modifiable risk factors of white matter hyperintensities is of particular
      relevance to reduce or delay dementia's onset.

PMID- 28492095
TI  - ?

PMID- 28492096
TI  - Physiological and self-reported disgust reactions to obesity.
AB  - There is accumulating evidence that disgust plays an important role in prejudice
      toward individuals with obesity, but that research is primarily based on self
      reported emotions. In four studies, we examined whether participants displayed a
      physiological marker of disgust (i.e. levator labii activity recorded using
      facial electromyography) in response to images of obese individuals, and whether
      these responses corresponded with their self-reported disgust to those images.
      All four studies showed the predicted self-reported disgust response toward
      images of obese individuals. Study 1 further showed that participants exhibited
      more levator activity to images of obese individuals than to neutral images.
      However, Studies 2-4 failed to provide any evidence that the targets' body size
      affected levator responses. These findings suggest that disgust may operate at
      multiple levels, and that the disgust response to images of obese individuals may
      be more of a cognitive-conceptual one than a physiological one.

PMID- 28492097
TI  - Optimal control of a social epidemic model with media coverage.
AB  - A new social epidemic model to depict alcoholism with media coverage is proposed
      in this paper. Some fundamental properties of the model including existence and
      positivity as well as boundedness of equilibria are investigated. Stability of
      all equilibria are studied. The existence of the optimal control pair and
      mathematical expressions of optimal control are obtained by Pontryagin's maximum
      principle. Numerical simulations are also performed to illustrate our results.
      Our results show that media coverage is an effective measure to quit drinking.

PMID- 28492098
TI  - L'evaluation d'impact sur la sante en Monteregie : un processus appuye sur le
      courtage de connaissances.
AB  - Le present article fait etat du modele de soutien a la prise de decision applique
      a l'evaluation d'impact sur la sante (EIS) en Monteregie, au Canada. Pour
      repondre a la volonte de soutenir l'elaboration de politiques et projets
      municipaux favorables a la sante et fondes sur les donnees probantes, la
      Direction de sante publique a mis en oeuvre une demarche d'EIS dont les
      fondements pratiques s'inspirent des experiences internationales en matiere d'EIS
      et dont les assises theoriques reposent sur le partage et le courtage de
      connaissances. L'experience monteregienne demontre que la strategie de courtage
      de connaissances appliquees a l'EIS encourage un partage respectueux des
      responsabilites et roles de chacune des parties prenantes et favorise
      l'utilisation des connaissances de sante publique dans la prise de decision
      municipale. Le courtage des connaissances permet de prendre en compte les enjeux
      locaux dans les analyses d'impact et dans les recommandations aux decideurs. En
      conclusion, il s'avere que l'implication des decideurs municipaux a la recherche
      de solutions favorables a la sante permet d'inscrire les donnees probantes a
      l'interieur des processus decisionnels et d'observer leur utilisation a plusieurs
      niveaux. L'evaluation des premieres experiences d'EIS revele en effet que les
      connaissances partagees repondent a des besoins immediats engendrant leur
      utilisation directe, contribuent a des changements de perception et de pratique a
      plus large echelle et font de la sante une valeur reconnue par les decideurs
      publics et promue aupres de leurs citoyens pour accroitre l'acceptabilite des
      initiatives municipales.

PMID- 28492099
TI  - 'Let the stars shine in peace!' Niels Bohr and stellar energy, 1929-1934.
AB  - Faced with various anomalies related to nuclear physics in particular, in 1929
      Niels Bohr suggested that energy might not be conserved in the atomic nucleus and
      the processes involving it. By this radical proposal he hoped not only to get rid
      of the anomalies but also saw a possibility to explain a puzzle in astrophysics,
      namely the energy generated by stars. Bohr repeated his suggestion of stellar
      energy arising ex nihilo on several occasions but without ever going into detail.
      In fact, it is not very clear what he meant or how seriously he took the stellar
      energy hypothesis. This paper relates Bohr's comments to the period's attempts to
      find a mechanism for stellar energy and also to the role played by astrophysics
      at the Copenhagen institute. Moreover, it looks at how Bohr's hypothesis was
      received not only by physicists but also by astronomers. In this regard the
      disciplinary status of astrophysics and its contemporary relation to the new
      quantum mechanics is of relevance. It turns out that, with very few exceptions,
      the hypothesis was met with silence by astronomers and astrophysicists concerned
      with the problem of stellar energy production. And yet, for a brief period of
      time it did have an impact on how physicists thought about the interior of the
      stars.

PMID- 28492100
TI  - Data mining in road crash analysis: the context of developing countries.
AB  - The recent advancements in the field of data mining have made vast progress in
      extracting new information and hidden patterns from large datasets which are
      often overlooked by the traditional statistical approaches. These methods focus
      on searching for new and interesting hypothesis which were previously unobserved.
      Road safety researchers working with the crash data from developed world have
      seen encouraging success in obtaining new insight into crash mechanism through
      data mining. An attempt was made in this study to apply these advance methods and
      evaluate their performance in manifesting crash causes for Bangladesh. The study
      applies hierarchical clustering to identify hazardous clusters, random forest to
      find important variables explaining each of these clusters, and classification
      and regression trees to unveil their respective crash mechanisms for the road
      crash data of Bangladesh. The results identified several new interesting
      relationships and acknowledged issues related to quality of data.

PMID- 28492101
TI  - Evaluation of 2016 MAGNIMS MRI criteria for dissemination in space in patients
      with a clinically isolated syndrome.
AB  - OBJECTIVES: We compared validity of 2010 McDonald and newly proposed 2016
      Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for
      dissemination in space (DIS) in predicting the conversion to clinically definite
      multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).
      METHODS: Between 2006 and 2016, we enrolled 170 patients who had a first clinical
      event suggestive of multiple sclerosis (MS) from seven referral hospitals in
      Korea. Patients were classified into two groups based on the main outcome at the
      last follow-up: CDMS converters, who experienced a second attack, and non
      converters. RESULTS: Of 170 patients with mean follow-up duration of 54 months,
      51% converted to CDMS. The sensitivity, specificity, accuracy, and positive and
      negative predictive values of 2010 McDonald criteria were 70.9%, 63.1%, 67.1%,
      66.3%, and 67.9%, and those for 2016 MAGNIMS criteria were 88.4%, 46.4%, 67.7%,
      62.8%, and 79.6%, respectively. When we excluded 80 patients who underwent
      disease-modifying therapy before the second clinical event, the specificity
      increased to 92.3% and 84.6%, but the sensitivity decreased to 58.8% and 82.4%
      for 2010 McDonald and 2016 MAGNIMS criteria, respectively. CONCLUSION: 2016
      MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher
      sensitivity but lower specificity than 2010 McDonald criteria in predicting
      conversion to CDMS in CIS patients.

PMID- 28492102
TI  - Determinants of fluid intelligence in healthy aging: Omega-3 polyunsaturated
      fatty acid status and frontoparietal cortex structure.
AB  - INTRODUCTION: Accumulating evidence indicates that cognitive decline depends not
      only upon changes in brain health, but critically, also upon nutritional status.
      Decline in fluid intelligence, one of the most debilitating aspects of cognitive
      aging, has been linked to omega-3 polyunsaturated fatty acid (PUFA) status;
      however, it is not known whether this phenomenon results from specific omega-3
      PUFAs acting on particular aspects of brain health. Therefore, this study aims to
      explore whether particular patterns of omega-3 PUFAs influence fluid intelligence
      by supporting specific neural structures. METHODS: We measured six plasma
      phospholipid omega-3 PUFAs, fluid intelligence, and regional gray matter volume
      in the frontal and parietal cortices in 100 cognitively intact older adults (65
      75 years old). A four-step mediation analysis was implemented using principal
      component analysis and multivariate linear regressions, adjusted for age, gender,
      education, and body mass index. RESULTS: The mediation analysis revealed that one
      pattern of omega-3 PUFAs, consisting of alpha-linolenic acid, stearidonic acid,
      and eicosatrienoic acid, was linked to fluid intelligence, and that total gray
      matter volume of the left frontoparietal cortex (FPC) fully mediated the
      relationship between this omega-3 PUFA pattern and fluid intelligence.
      DISCUSSION: These data demonstrate that fluid intelligence may be optimally
      supported by specific omega-3 PUFAs through preservation of FPC gray matter
      structure in cognitively intact older adults. This report provides novel evidence
      for the benefits of particular omega-3 PUFA patterns on fluid intelligence and
      underlying gray matter structure.

PMID- 28492103
TI  - Amphipathic secondary structure elements and putative cholesterol recognizing
      amino acid consensus (CRAC) motifs as governing factors of highly specific matrix
      protein interactions with raft-type membranes in enveloped viruses.

PMID- 28492104
TI  - Oxytocin and Vasopressin: Powerful Regulators of Social Behavior.
AB  - For many, the terms oxytocin and vasopressin immediately evoke images of animals
      interacting with one another, as both of these neuropeptides have been implicated
      as being part of the neurochemical "glue" that socially binds animals. However,
      social environments and social interactions are complex and include behaviors
      that bring animals together as well as behaviors that keep animals apart. It is
      at the intersection of social context, social experience, and an individual's sex
      that oxytocin and vasopressin act to modulate social behavior and social
      cognition. In this review, this complexity will be explored across mammalian
      species, with a focus on social memory, cooperative behaviors, and competitive
      behaviors. Implications for humans as well as future directions will also be
      considered.

PMID- 28492105
TI  - Metastatic spinal cord compression as the first sign of malignancy.
AB  - Background and purpose - Metastatic spinal cord compression (MSCC) as the initial
      manifestation of malignancy (IMM) limits the time for diagnostic workup; most
      often, treatment is required before the final primary tumor diagnosis. We
      evaluated neurological outcome, complications, survival, and the manner of
      diagnosing the primary tumor in patients who were operated for MSCC as the IMM.
      Patients and methods - Records of 69 consecutive patients (51 men) who underwent
      surgery for MSCC as the IMM were reviewed. The patients had no history of cancer
      when they presented with pain (n = 2) and/or neurological symptoms (n = 67).
      Results - The primary tumor was identified in 59 patients. In 10 patients, no
      specific diagnosis could be established, and they were therefore defined as
      having cancer of unknown primary tumor (CUP). At the end of the study, 16
      patients were still alive (median follow-up 2.5 years). The overall survival time
      was 20 months. Patients with CUP had the shortest survival (3.5 months) whereas
      patients with prostate cancer (6 years) and myeloma (5 years) had the longest
      survival. 20 of the 39 patients who were non-ambulatory preoperatively regained
      walking ability, and 29 of the 30 ambulatory patients preoperatively retained
      their walking ability 1 month postoperatively. 15 of the 69 patients suffered
      from a total of 20 complications within 1 month postoperatively. Interpretation -
      Postoperative survival with MSCC as the IMM depends on the type of primary tumor.
      Surgery in these patients maintains and improves ambulatory function.

PMID- 28492107
TI  - Aborted Tracheo-esophageal Fistula in a Neonate.
AB  - Esophageal atresia (EA) is an uncommon congenital anomaly which is often
      associated with a tracheoesophageal fistula. An isolated EA is a rarer anomaly
      and its diagnosis has implications for the ongoing treatment and outcome of the
      infant. For the first time, we report a case of a premature newborn with a pure
      EA and a tracheal diverticulum, containing both respiratory and esophageal
      mucosa. We have termed this an aborted trachea-esophageal fistula. Recognition of
      these very rare variations of foregut anomalies may contribute to our
      understanding of their pathogenesis.

PMID- 28492106
TI  - Higher risk of revision for infection using systemic clindamycin prophylaxis than
      with cloxacillin.
AB  - Background and purpose - Clindamycin has not been compared with other antibiotics
      for prophylaxis in arthroplasty. Since 2009, the Swedish Knee Arthroplasty
      Register (SKAR) has been collecting information on the prophylactic antibiotic
      regime used at every individual operation. In Sweden, when there is allergy to
      penicillin, clindamycin has been the recommended alternative. We examined whether
      there were differences in the rate of revision due to infection depending on
      which antibiotic was used as systemic prophylaxis. Patients and methods -
      Patients who had a total knee arthroplasty (TKA) performed due to osteoarthritis
      (OA) during the years 2009-2015 were included in the study. Information on which
      antibiotic was used was available for 80,018 operations (55,530 patients).
      Survival statistics were used to calculate the rate of revision due to infection
      until the end of 2015, comparing the group of patients who received cloxacillin
      with those who received clindamycin as systemic prophylaxis. Results -
      Cloxacillin was used in 90% of the cases, clindamycin in 7%, and cephalosporins
      in 2%. The risk of being revised due to infection was higher when clindamycin was
      used than when cloxacillin was used (RR =1.5, 95% CI: 1.2-2.0; p = 0.001). There
      was no significant difference in the revision rate for other causes (p = 0.2).
      Interpretation - We advise that patients reporting allergic reaction to
      penicillin should have their allergic history explored. In the absence of a clear
      history of type-I allergic reaction (e.g. urticaria, anaphylaxis, or
      bronchospasm), we suggest the use of a third-generation cephalosporin instead of
      clindamycin as perioperative prophylaxis when undergoing a TKR. No recommendation
      can be given regarding patients with type-1 allergy.

PMID- 28492108
TI  - Three-dimensional Simulation of Quantitative Ultrasound in Cancellous Bone Using
      the Echographic Response of a Metallic Pin.
AB  - Degenerative discopathy is a common pathology that may require spine surgery. A
      metallic cylindrical pin is inserted into the vertebral body to maintain soft
      tissues and may be used as a reflector of ultrasonic wave to estimate bone
      density. The first aim of this paper is to validate a three-dimensional (3-D)
      model to simulate the ultrasonic propagation in a trabecular bone sample in which
      a metallic pin has been inserted. We also aim at determining the effect of
      changes of bone volume fraction (BV/TV) and of positioning errors on the
      quantitative ultrasound (QUS) parameters in this specific configuration. The
      approach consists in coupling finite-difference time-domain simulation with X-ray
      microcomputed tomography. The correlation coefficient between experimental and
      simulated speed of sound (SOS)-respectively, broadband ultrasonic attenuation
      (BUA)-was equal to 0.90 (respectively, 0.55). The results show a significant
      correlation of SOS with BV/TV ( R = 0.82), while BUA values exhibit a nonlinear
      behavior versus BV/TV. The orientation of the pin should be controlled with an
      accuracy of around 1 degrees  to obtain accurate results. The results indicate
      that using the ultrasonic wave reflected by a pin has a potential to estimate the
      bone density. SOS is more reliable than BUA due to its lower sensitivity to the
      tilt angle.

PMID- 28492109
TI  - Revisiting the role of dissimilarity of host communities in driving dissimilarity
      of ectoparasite assemblages: non-linear vs linear approach.
AB  - We revisited the role of dissimilarity of host assemblages in shaping
      dissimilarity of flea assemblages using a non-linear approach. Generalized
      dissimilarity models (GDMs) were applied using data from regional surveys of
      fleas parasitic on small mammals in four biogeographical realms. We compared (1)
      model fit, (2) the relative effects of host compositional and phylogenetic
      turnover and geographic distance on flea compositional and phylogenetic turnover,
      and (3) the rate of flea turnover along gradients of host turnover and geographic
      distance with those from earlier application of a linear approach. GDMs
      outperformed linear models in explaining variation in flea species turnover and
      host dissimilarity was the best predictor of flea dissimilarity, irrespective of
      scale. The shape of the relationships between flea compositional turnovers along
      host compositional turnover was similar in all realms, whereas turnover along
      geographic distance differed among realms. In contrast, the rate of flea
      phylogenetic turnover along gradients of host phylogenetic turnover differed
      among realms, whereas flea phylogenetic turnover did not depend on geographic
      distance in any realm. We demonstrated that a non-linear approach (a) explained
      spatial variation in parasite community composition better than and (b) revealed
      patterns that were obscured by earlier linear analyses.

PMID- 28492110
TI  - Characteristics of influential peers in the eyes of secondary school students: a
      mixed method study.
AB  - : Aim It is the aim of this study to explore the characteristics of influential
      peers identified by schoolmates, and the mechanism by which they exert their
      influence on their peers. BACKGROUND: Adolescent crowds are a salient influence
      on the health-risk behaviors of peers, contributing to adolescent substance use
      such as drinking alcohol, smoking cigarettes, and taking drugs. METHODS: A mixed
      method study. Three schools granted us access to students and those who had been
      nominated as influential by their peers. The students were asked to nominate and
      indicated the characteristics of peers whom they considered influential in a
      quantitative study. Those peers whom they considered influential were invited to
      take part in focus group interviews. A total of six focus group interviews were
      conducted, comprised of two groups from each school, with an average of seven
      participants in each group. Findings Students considered caring and friendliness
      (91.0%), being a buddy (88.5%), and entertaining/humor (86.8%) as the top three
      characteristics of influential peers. The interviews revealed that the students
      believed that they are influential because of their cheerfulness and humor,
      considerateness, ability to communicate, popularity and sociability, sincerity
      and trustworthiness, and because they possess the characteristics of a leader.
      They also believed that their power to influence came about through their
      helpfulness, accommodation, and the closeness of their relationships. Their
      influence was manifested in both positive and negative ways on the academic
      pursuits and health-risk behaviors of their peers. In order to engage at-risk
      students in health promotion programs, it is important to identify their
      influential peers, and to understand how adolescent friends may help one another
      to resist behaviors that pose a risk to their health.

PMID- 28492111
TI  - A comparison of disease susceptibility and innate immune response between diploid
      and triploid Atlantic salmon (Salmo salar) siblings following experimental
      infection with Neoparamoeba perurans, causative agent of amoebic gill disease.
AB  - Few studies have focussed on the health and immunity of triploid Atlantic salmon
      and therefore much is still unknown about their response to commercially
      significant pathogens. This is important if triploid stocks are to be considered
      for full-scale commercial production. This study aimed to investigate and compare
      the response of triploid and diploid Atlantic salmon to an experimental challenge
      with Neoparamoeba perurans, causative agent of amoebic gill disease (AGD). This
      disease is economically significant for the aquaculture industry. The results
      indicated that ploidy had no significant effect on gross gill score or gill
      filaments affected, while infection and time had significant effects. Ploidy,
      infection and time did not affect complement or anti-protease activities. Ploidy
      had a significant effect on lysozyme activity at 21 days post-infection (while
      infection and time did not), although activity was within the ranges previously
      recorded for salmonids. Stock did not significantly affect any of the parameters
      measured. Based on the study results, it can be suggested that ploidy does not
      affect the manifestation or severity of AGD pathology or the serum innate immune
      response. Additionally, the serum immune response of diploid and triploid
      Atlantic salmon may not be significantly affected by amoebic gill disease.

PMID- 28492112
TI  - Undergraduate antibiotic stewardship training: Are we leaving our future
      prescribers 'flapping in the wind'?

PMID- 28492113
TI  - Health research and safeguards: The South African journey.
AB  - Health research, as a social good, needs to be conducted in the interests of the
      common good. Because of the unfortunate exploitation of research participants
      globally, safeguards for protections are necessary. Most international codes and
      guidelines originated as responses to the abuse and mistreatment of research
      subjects. By the 1890s, antivivisectionists were already calling for laws to
      protect children, as a result of the increasing numbers of institutionalised
      children being subjected to vaccine experiments in Europe and the USA. Just after
      the turn of the century, the first attempt to test a polio vaccine was thwarted
      after the American Public Health Association condemned the programme. In South
      Africa, medical scientists were busy with discoveries and innovations as far back
      as the 1800s. In December 1967, the historic first human heart transplant was
      undertaken in Cape Town. Although it is unclear how much research preceded this
      procedure, there is no doubt that the operation was done in a research setting,
      and it had a far-reaching impact.

PMID- 28492114
TI  - Assisted suicide and assisted voluntary euthanasia: Stransham-Ford High Court
      case overruled by the Appeal Court - but the door is left open.
AB  - Whether persons wishing to have doctor-assisted suicide or voluntary active
      euthanasia may make a court application based on their rights in the Constitution
      has not been answered by the Appeal Court. Therefore, if Parliament does not
      intervene beforehand, such applications can be made - provided the applicants
      have legal standing, full arguments are presented regarding local and foreign
      law, and the application evidence is comprehensive and accurate. The Appeal Court
      indicated that the question should be answered by Parliament because 'issues
      engaging profound moral questions beyond the remit of judges to determine, should
      be decided by the representatives of the people of the country as a whole'.
      However, the Government has not implemented any recommendations on doctor
      assisted suicide and voluntary active euthanasia made by the South African Law
      Commission 20 years ago. The courts may still develop the law on doctor-assisted
      death, which may take into account developments in medical practice. Furthermore,
      'the possibility of a special defence for medical practitioners or carers would
      arise and have to be explored'.

PMID- 28492115
TI  - Human dignity and the future of the voluntary active euthanasia debate in South
      Africa.
AB  - The issue of voluntary active euthanasia was thrust into the public policy arena
      by the Stransham-Ford lawsuit. The High Court legalised voluntary active
      euthanasia - however, ostensibly only in the specific case of Mr Stransham-Ford.
      The Supreme Court of Appeal overturned the High Court judgment on technical
      grounds, not on the merits. This means that in future the courts can be
      approached again to consider the legalisation of voluntary active euthanasia. As
      such, Stransham-Ford presents a learning opportunity for both sides of the
      legalisation divide. In particular, conceptual errors pertaining to human dignity
      were made in Stransham-Ford, and can be avoided in future. In this article, I
      identify these errors and propose the following three corrective principles to
      inform future debate on the subject: (i) human dignity is violable; (ii) human
      suffering violates human dignity; and (iii) the 'natural' causes of suffering due
      to terminal illness do not exclude the application of human dignity.

PMID- 28492116
TI  - Ethical and legal perspectives on the medical practitioners use of social media.
AB  - Use of social media has increased exponentially throughout the world. Social
      media provides a platform for building social and professional relationships that
      can be used by all, including healthcare professionals. Alongside the benefits of
      creating networks and spreading information wider and faster than is possible
      with traditional communication channels, however, it presents ethical and legal
      challenges. For health professionals, it poses a threat to confidentiality and
      privacy owed to patients, colleagues and employers. It is vital for health
      professionals to acknowledge that the same ethical and legal standards apply both
      online and offline, and that they are accountable to professional bodies and the
      law for their online activities. This article seeks to explore the ethical and
      legal pitfalls facing health professionals using social media platforms.
      Importantly, it seeks to create awareness about the cyberpsychology phenomenon
      called the 'online disinhibition effect', responsible for lowering restraint
      during online activities.

PMID- 28492117
TI  - Biobanks in South Africa: A global perspective on privacy and confidentiality.
AB  - The Universal Declaration of Bioethics and Human Rights (UDBHR) of the United
      Nations Educational, Scientific and Cultural Organization (UNESCO) was adopted
      unanimously in 2005 by the world community as a universal guideline, according to
      which members of the global community were accountable to each other. Research
      results from UNESCO show that the UDBHR has had little or no impact in South
      Africa (SA). The primary objective of this article is to promote awareness of the
      UDBHR in SA and Africa by focusing on Article 9 of the Declaration, which accepts
      the right to privacy and confidentiality. For this objective to be relevant in
      the SA context, depends on whether the guidelines of the National Department of
      Health's Ethics in Health Research: Principles, Processes and Structures of 2015
      acknowledge biobanks of the universally accepted ethical guidelines on privacy
      and confidentiality of autonomous persons and whether these guidelines are
      broadly in accordance with global bioethical guidelines.

PMID- 28492118
TI  - Legal liability for failure to prevent pregnancy (wrongful pregnancy).
AB  - Can the conception of a child ever constitute damage recoverable in law? This
      article considers the liability of healthcare practitioners for failing to
      prevent a pregnancy. Developments leading to the recognition of wrongful
      pregnancy as a cause of (legal) action in South Africa (SA), are briefly
      outlined. The salient points of the relevant judgments by SA courts are set out
      to expose the rationale underlying the judgments and to highlight that
      recognition of liability for wrongful pregnancy resulted from an application of
      fair and equitable principles of general application. Conduct that could expose
      practitioners to liability is identified from reported cases and inferred from
      general principles laid down in case law.

PMID- 28492119
TI  - Paraquat poisoning: Acute lung injury - a missed diagnosis.
AB  - Paraquat is a herbicide of great toxicological importance because it is
      associated with high mortality rates, mainly due to respiratory failure. We
      report the case of a 28-year-old man admitted to the casualty department at
      Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of
      vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance,
      later identified as paraquat, together with an unknown amount of alcohol, in a
      suicide attempt. He developed respiratory distress associated with lung
      parenchymal infiltrates that required ventilatory support and later a spontaneous
      pneumothorax, and died in the intensive care unit. We discuss the importance of a
      high index of suspicion of paraquat poisoning in rural areas, where paraquat is
      readily available as a herbicide on farms, in patients with a similar
      presentation. We further stress the importance of identifying the classic
      radiological progression after paraquat poisoning, to help avoid a delay in
      diagnosis if the culprit substance is not known (as happened in our case).
      Lastly, we look at the importance of avoiding oxygen supplementation, and early
      administration of immunosuppressive therapy, to improve outcome.

PMID- 28492120
TI  - A rare case of massive hepatosplenomegaly due to acute lymphoblastic leukemia in
      pregnancy.
AB  - Acute lymphoblastic leukaemia (ALL) is rarely seen in pregnancy. Massive
      hepatosplenomegaly as a presentation of ALL has not been described previously in
      any patient population. A 30-year-old pregnant woman presented at 16 weeks'
      gestation with epistaxis, jaundice, diffuse abdominal pain and distension,
      massive hepatosplenomegaly and peripheral oedema. On the basis of blood tests,
      bone marrow biopsy and imaging, a diagnosis of ALL complicated by massive
      hepatosplenomegaly with splenic infarctions was made. The patient was referred to
      oncology for appropriate chemotherapy.

PMID- 28492121
TI  - South African medical students' perceptions and knowledge about antibiotic
      resistance and appropriate prescribing: Are we providing adequate training to
      future prescribers?
AB  - BACKGROUND: Education of medical students has been identified by the World Health
      Organization as an important aspect of antibiotic resistance (ABR) containment.
      Surveys from high-income countries consistently reveal that medical students
      recognise the importance of antibiotic prescribing knowledge, but feel
      inadequately prepared and require more education on how to make antibiotic
      choices. The attitudes and knowledge of South African (SA) medical students
      regarding ABR and antibiotic prescribing have never been evaluated. OBJECTIVE: To
      evaluate SA medical students' perceptions, attitudes and knowledge about
      antibiotic use and resistance, and the perceived quality of education relating to
      antibiotics and infection. METHODS: This was a cross-sectional survey of final
      year students at three medical schools, using a 26-item self-administered
      questionnaire. The questionnaires recorded basic demographic information,
      perceptions about antibiotic use and ABR, sources, quality, and usefulness of
      current education about antibiotic use, and questions to evaluate knowledge. Hard
      copy surveys were administered during whole-class lectures. RESULTS: A total of
      289 of 567 (51%) students completed the survey. Ninety-two percent agreed that
      antibiotics are overused and 87% agreed that resistance is a significant problem
      in SA - higher proportions than those who thought that antibiotic overuse (63%)
      and resistance (61%) are problems in the hospitals where they had worked
      (p<0.001). Most reported that they would appreciate more education on appropriate
      use of antibiotics (95%). Only 33% felt confident to prescribe antibiotics, with
      similar proportions across institutions. Overall, prescribing confidence was
      associated with the use of antibiotic prescribing guidelines (p=0.003),
      familiarity with antibiotic stewardship (p=0.012), and more frequent contact with
      infectious diseases specialists (p<0.001). There was an overall mean correct
      score of 50% on the knowledge questionnaire, with significant differences between
      institutions. Students who used antibiotic prescribing guidelines and found their
      education more useful scored higher on knowledge questionnaires. CONCLUSION:
      There are low levels of confidence with regard to antibiotic prescribing among
      final-year medical students in SA, and most students would like more education in
      this area. Perceptions that ABR is less of a problem in their local setting may
      contribute to inappropriate prescribing behaviours. Differences exist between
      medical schools in knowledge about antibiotic use, with suboptimal scores across
      institutions. The introduction and use of antibiotic prescribing guidelines and
      greater contact with specialists in antibiotic prescribing may improve
      prescribing behaviours.

PMID- 28492122
TI  - Critical care admission of South African (SA) surgical patients: Results of the
      SA Surgical Outcomes Study.
AB  - BACKGROUND: Appropriate critical care admissions are an important component of
      surgical care. However, there are few data describing postoperative critical care
      admission in resource-limited low- and middle-income countries. OBJECTIVE: To
      describe the demographics, organ failures, organ support and outcomes of non
      cardiac surgical patients admitted to critical care units in South Africa (SA).
      METHODS: The SA Surgical Outcomes Study (SASOS) was a 7-day national,
      multicentre, prospective, observational cohort study of all patients >=16 years
      of age undergoing inpatient non-cardiac surgery between 19 and 26 May 2014 at 50
      government-funded hospitals. All patients admitted to critical care units during
      this study were included for analysis. RESULTS: Of the 3 927 SASOS patients, 255
      (6.5%) were admitted to critical care units; of these admissions, 144 (56.5%)
      were planned, and 111 (43.5%) unplanned. The incidence of confirmed or strongly
      suspected infection at the time of admission was 35.4%, with a significantly
      higher incidence in unplanned admissions (49.1 v. 24.8%, p<0.001). Unplanned
      admission cases were more frequently hypovolaemic, had septic shock, and required
      significantly more inotropic, ventilatory and renal support in the first 48 hours
      after admission. Overall mortality was 22.4%, with unplanned admissions having a
      significantly longer critical care length of stay and overall mortality (33.3 v.
      13.9%, p<0.001). CONCLUSION: The outcome of patients admitted to public sector
      critical care units in SA is strongly associated with unplanned admissions.
      Adequate 'high care-dependency units' for postoperative care of elective surgical
      patients could potentially decrease the burden on critical care resources in SA
      by 23%. This study was registered on ClinicalTrials.gov (NCT02141867).

PMID- 28492123
TI  - Factors associated with contracting malaria in Ward 29 of Shamva District,
      Zimbabwe, 2014.
AB  - BACKGROUND: Malaria cases at Wadzanayi Clinic in Shamva District, Zimbabwe,
      increased drastically, surpassing the epidemic threshold, in week four of
      December 2013. This rise was sustained, which necessitated an investigation of
      the outbreak. OBJECTIVES: To identify risk factors and system weaknesses to
      improve epidemic preparedness and response. METHODS: An unmatched 1:1 case
      control study was conducted in Ward 29 of Shamva District in Zimbabwe. Epidemic
      preparedness and response were assessed using the Zimbabwean epidemic
      preparedness and response guidelines. RESULTS: The sociodemographic
      characteristics of all participants were similar, except for gender. The risk
      factors for contracting malaria were performing early morning chores (odds ratio
      (OR) 2.75; 95% confidence interval (CI) 1.20 - 6.32), having a body of water near
      the home (OR 3.41; 95% CI 1.62 - 7.20) and having long grass near the home (OR
      2.61; 95% CI 1.10 - 6.37). Protective factors were staying indoors at night (OR
      0.13; 95% CI 0.06 - 0.28) and staying in a sprayed home (OR 0.36; 95% CI 0.21 -
      0.92). All cases were diagnosed with a malaria rapid diagnostic test. All
      complicated cases were treated with quinine. Four out of 58 uncomplicated cases
      were treated with quinine. The rest were treated with co-artemether. There was no
      documentation of the outbreak response by the district health executive.
      Respraying (indoor residual spraying) was carried out, with a coverage of 78% of
      rooms sprayed. One nurse out of seven at Wadzanayi Clinic was trained in
      integrated disease surveillance and response, and malaria case management.
      District malaria thresholds were outdated. Malaria commodities such as drugs and
      sprays did not have reorder limits. CONCLUSION: This study re-emphasises the
      importance of environmental- and personal-level factors as determinants of
      malaria. Poor out-break preparedness and response may have propagated the malaria
      outbreak in this setting. Health education and the use of mosquito repellants
      should be emphasised. Larvicide may reduce the malaria burden. Epidemic
      preparedness and response need to be strengthened. Outbreak investigation remains
      important. This study emphasises the need for malaria interventions to be
      tailored to locally prevailing determinants to avert outbreaks.

PMID- 28492124
TI  - Predicting postoperative haemoglobin changes after burn surgery.
AB  - BACKGROUND: Burn surgery is associated with significant blood loss and fluid
      shifts that cause rapid haemoglobin (Hb) changes during and after surgery.
      Understanding the relationship between intraoperative and postoperative (day 1)
      Hb changes may assist in avoiding postoperative anaemia and unnecessary peri
      operative blood transfusion. OBJECTIVE: To describe the Hb changes into the first
      day after burn surgery and to identify factors predictive of Hb changes that
      would guide blood transfusion decisions. METHODS: This was a single-institution,
      retrospective cohort study that included 158 patients who had undergone burn
      surgery. Hb was measured at the start and end of surgery, and on the first day
      (16 - 32 hours) after surgery, and the results were analysed. Peri-operative
      factors (Hb at the end of surgery, total body surface area operated on (TBSA-op),
      fluid administration and intraoperative blood administration) were evaluated to
      determine their association with Hb changes on the first day after surgery.
      RESULTS: The mean (standard deviation) preoperative Hb was 10.6 (2.29) g/dL, the
      mean postoperative Hb was 9.4 (2.01) g/dL, and the mean Hb on the first day after
      surgery was 9.2 (2.19) g/dL. Median total burn surface area was 7% (interquartile
      range 9%, min. 1%, max. 45%), with a mean body surface area operated on
      (debridement area plus donor area) of 9.7%. Of the 158 patients, 26 (16%) had an
      Hb <7 g/dL (transfusion trigger) on the first day after surgery. For patients
      with a high (>=9 g/dL), intermediate (>=7 - <9 g/dL), or low (<7 g/dL) Hb
      measurement at the end of burn surgery, those with an Hb below the transfusion
      trigger on the first day after burn surgery were 0%, 27%, and 75%, respectively.
      End-of-surgery Hb and TBSA-op strongly predicted the first day Hb level. In the
      intermediate group, 55% of patients with a TBSA-op >=11% had an Hb below the
      transfusion trigger on the first day after surgery. CONCLUSION: Hb at the end of
      burn surgery was the best predictor of Hb on the first day after surgery.
      Patients with an Hb <7 g/dL remained as such on the first postoperative day. Half
      of the patients with an end-of-surgery Hb >=7 - <9 g/dL and who had >=11% TBSA-op
      had an Hb <7 g/dL on the first postoperative day.

PMID- 28492125
TI  - Influence of HIV and other risk factors on tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) notification in South Africa has increased six-fold
      over the past two decades, mainly because of the HIV epidemic. OBJECTIVES: To
      describe the sociodemographic and outcome characteristics of TB patients, and to
      identify risk factors associated with TB treatment outcomes stratified by HIV
      status. METHODS: A cross-sectional study was used to analyse data from the Cape
      Town Metro East geographical service area (GSA) electronic TB register (ETR.Net),
      including adult patients aged >=15 years who initiated TB treatment between 1
      July 2011 and 30 June 2012. RESULTS: TB case notification in the GSA was 922 per
      100 000 population. Of the 12 672 TB patients registered, 50.5% were co-infected
      with HIV. The death rate in co-infected patients was 5.4% v. 2.8% in HIV-negative
      patients, the rate of treatment success 66.6% v. 73.5%, and the rate of
      unfavourable treatment outcome 28.1% v. 23.7%. The Khayelitsha subdistrict had
      the highest proportion of TB burden (37.0%) and co-infection (47.6%). Fourteen
      percent of patients had extrapulmonary TB, 65.9% of whom were co-infected with
      HIV. In the multivariate analysis, HIV infection (relative risk (RR) 1.2),
      retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were
      significantly associated with unfavourable treatment outcome. The Eastern (RR
      0.9) and Northern (RR 0.7) subdistricts were less likely to have unfavourable
      outcomes compared with Khayelitsha. In the stratified analysis, retreatment and
      smear not done were significant risk factors for an unfavourable treatment
      outcome in both co-infected and HIV-negative patients. CONCLUSIONS: The burdens
      of both TB and co-infection were high in this community, although HIV prevalence
      varied. Mortality was higher and treatment completion lower in co-infected
      patients than in those who were HIV-negative. Co-infection, previous TB treatment
      and smear not done were significant risk factors for an unfavourable outcome in
      all patients.

PMID- 28492126
TI  - Bacteria isolated from the airways of paediatric patients with bronchiectasis
      according to HIV status.
AB  - BACKGROUND: Knowledge of which bacteria are found in the airways of paediatric
      patients with bronchiectasis unrelated to cystic fibrosis (CF) is important in
      defining empirical antibiotic guidelines for the treatment of acute infective
      exacerbations. OBJECTIVE: To describe the bacteria isolated from the airways of
      children with non-CF bronchiectasis according to their HIV status. METHODS:
      Records of children with non-CF bronchiectasis who attended the paediatric
      pulmonology clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg,
      South Africa, from April 2011 to March 2013, or were admitted to the hospital
      during that period, were reviewed. Data collected included patient demographics,
      HIV status, and characteristics of the airway samples and types of bacteria
      isolated. RESULTS: There were 66 patients with non-CF bronchiectasis over the 2
      year study period. The median age was 9.1 years (interquartile range 7.2 - 12.1).
      The majority of patients (78.8%) were HIV-infected. A total of 134 samples was
      collected (median 1.5 per patient, range 1 - 7), of which 81.3% were expectorated
      or induced sputum samples. Most bacteria were Gram negatives (72.1%). Haemophilus
      influenzae was the most common bacterium identified (36.0%), followed by
      Streptococcus pneumoniae (12.6%), Moraxella catarrhalis (11.1%) and
      Staphylococcus aureus (10.6%). There were no differences between HIV-infected and
      uninfected patients in prevalence or type of pathogens isolated. CONCLUSION:
      Bacterial isolates from the airways of children with non-CF bronchiectasis were
      similar to those in other paediatric populations and were not affected by HIV
      status.

PMID- 28492128
TI  - Validating the utilisation of venous bicarbonate as a predictor of acute kidney
      injury in crush syndrome from sjambok injuries.
AB  - BACKGROUND: Crush injury secondary to sjambok beatings is a well-described
      phenomenon in southern Africa. Owing to a number of factors, it can result in
      acute kidney injury (AKI). In 1992, Muckart et al. described a risk
      stratification system using venous bicarbonate (VB) that can be used in the
      management of these patients. OBJECTIVE: To validate this score in the modern era
      of AKI risk stratification. METHODS: A retrospective study was performed on a
      local trauma database from June 2010 to December 2012. All patients with crush
      injury from sjambok/blunt instrument beatings were included in the analysis. VB
      was compared with the Kidney Disease Improving Global Outcomes scoring system for
      AKI. Serum base excess (BE) and creatine kinase were also examined as biomarkers.
      The endpoints were the need for renal replacement therapy (RRT) and mortality.
      RESULTS: Three hundred and ten patients were included. The overall mortality rate
      was 1.9%, 14.8% of patients had AKI, and 3.9% required RRT. Both VB and BE
      performed well in RRT prediction, with areas under the receiver operating
      characteristic curve of 0.847 (95% confidence interval (CI) 0.756 - 0.938;
      p<0.001) and 0.871 (95% CI 0.795 - 0.947; p<0.001), respectively. The sensitivity
      and specificity of BE were 83.3% and 80.2% at an optimal cut-point of -7.25
      mmol/L, while those of VB were 83.3% and 79.5% at an optimal cut-point of 18.85
      mmol/L. VB was significantly different across the AKI risk groups (p<0.001), in
      keeping with the original Muckart risk stratification system. CONCLUSION: The
      risk stratification score using VB is valid and should continue to be used as a
      tool in the management of patients with sjambok injuries. BE performs well in
      predicting the need for RRT, with a value of <-7.25 mmol/L indicating severe
      injury.

PMID- 28492127
TI  - Obstructive pulmonary disease in patients with previous tuberculosis:
      Pathophysiology of a community-based cohort.
AB  - BACKGROUND: An association between chronic airflow limitation (CAL) and a history
      of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies,
      but the mechanisms responsible for this association are unclear. It is debated
      whether CAL in this context should be viewed as chronic obstructive pulmonary
      disease (COPD) or a separate phenotype. OBJECTIVE: To compare lung physiology and
      high-resolution computed tomography (HRCT) findings in subjects with CAL and
      evidence of previous (healed) PTB with those in subjects with smoking-related
      COPD without evidence of previous PTB. METHODS: Subjects with CAL identified
      during a Burden of Obstructive Lung Disease (BOLD) study performed in South
      Africa were studied. Investigations included questionnaires, lung physiology
      (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT
      scans to assess bronchial anatomy and the presence of emphysema (<-950 HU), gas
      trapping (<-860 HU) and fibrosis (>-200 HU). Findings in subjects with a past
      history and/or HRCT evidence of PTB were compared with those in subjects without
      these features. RESULTS: One hundred and seven of 196 eligible subjects (54.6%)
      were enrolled, 104 performed physiology tests and 94 had an HRCT scan. Based on
      history and HRCT findings, subjects were categorised as no previous PTB (NPTB,
      n=31), probable previous PTB (n=33) or definite previous PTB (DPTB, n=39).
      Subjects with DPTB had a lower diffusing capacity (Delta=-17.7%; p=0.001) and
      inspiratory capacity (Delta=-21.5%; p=0.001) than NPTB subjects, and higher gas
      trapping and fibrosis but not emphysema scores (Delta=+6.2% (p=0.021), +0.36%
      (p=0.017) and +3.5% (p=0.098), respectively). CONCLUSIONS: The mechanisms of CAL
      associated with previous PTB appear to differ from those in the more common
      smoking-related COPD and warrant further study.

PMID- 28492129
TI  - Codeine misuse and dependence in South Africa: Perspectives of addiction
      treatment providers.
AB  - BACKGROUND: General practitioners are referring patients with codeine-related
      problems to specialist treatment facilities, but little is known about the
      addiction treatment providers, the kinds of treatment they provide, and whether
      training or other interventions are needed to strengthen this sector. OBJECTIVES:
      To investigate the perspectives of addiction treatment providers regarding
      treatment for codeine misuse or dependence. METHOD: Twenty addiction treatment
      providers linked to the South African Community Epidemiology Network on Drug Use
      and the South African Addiction Medicine Society were contacted telephonically
      and asked 20 questions. RESULTS: While many participants had received training in
      pharmacological management of individuals with opioid dependence, only two had
      received specific training on codeine management. Between half and two-thirds of
      the treatment settings they worked in provided detoxification, pharmacotherapy,
      psychosocial treatment and aftercare. Very few treatment settings offered long
      term treatment for codeine misuse and dependence. Participants indicated that
      over half of their codeine patients entered treatment for intentional misuse for
      intoxication, and dependence resulting from excessive or long-term use. The main
      barriers to patients entering treatment were seen as denial of having a problem,
      not being ready for change, mental health problems, stigma, and affordability of
      treatment. Participants identified a need for further training in how to manage
      withdrawal and detoxification, treatment modalities including motivational
      interviewing, and relapse prevention. CONCLUSIONS: Gaps in training among
      treatment providers need to centre on how to manage withdrawal from codeine use
      and detoxification, motivational interviewing and relapse prevention.
      Interventions are needed to address barriers to entering treatment, including
      user denial.

PMID- 28492130
TI  - Osteogenesis imperfecta type 3 in South Africa: Causative mutations in FKBP10.
AB  - BACKGROUND: A relatively high frequency of autosomal recessively inherited
      osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black
      southern African population. Affected persons may be severely handicapped as a
      result of frequent fractures, progressive deformity of the tubular bones and
      spinal malalignment. OBJECTIVE: To delineate the molecular basis for the
      condition. METHODS: Molecular investigations were performed on 91 affected
      persons from seven diverse ethnolinguistic groups in this population. RESULTS:
      Following polymerase chain reaction amplification and direct cycle sequencing,
      FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The
      homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected
      individuals in the study cohort. Haplotype analysis suggests that this mutation
      is identical among these OI-3-affected persons by descent, thereby confirming
      that they had a common ancestor. Compound heterozygosity of this founder mutation
      was observed, in combination with three different deleterious FKBP10 mutations,
      in six additional persons in the cohort. Four of these individuals had the
      c.831delC mutation. CONCLUSION: The burden of the disorder, both in frequency and
      severity, warrants the establishment of a dedicated service for molecular
      diagnostic confirmation and genetic management of persons and families with OI in
      southern Africa.

PMID- 28492132
TI  - The Determination of Sugars in Dairy Products: Development of a New Standard
      Method for the International Dairy Federation and the Internal Organization for
      Standardization.
AB  - A method using high-performance anion-exchange chromatography (HPAEC) with a
      pulsed amperometric detector (PAD) for the determination of mono- and
      disaccharides is described. The method was accepted by the International Dairy
      Federation and the Internal Organization for Standardization as a new work item
      for the determination of sugars in dairy matrixes, and the Milk and Milk Products
      technical committee of ISO/TC 34/SC 5 accepted the topic "Milk and milk products 
      Determination of the sugar contents - High-performance anion-exchange
      chromatographic method (HPAEC-PAD)" as a new work item. The proposed method
      consists of an aqueous ethanol extraction of the sugars in the dairy sample,
      followed by clarification with Carrez I and II reagents. The clarified filtrate
      is diluted and then directly introduced in the HPAEC-PAD system for
      quantification of the sugars. A single-laboratory validation of the proposed
      method has been scheduled for spring 2017.

PMID- 28492133
TI  - Current Assays to Determine Free 25-Hydroxyvitamin D in Serum.
AB  - The 25-hydroxylated metabolite of vitamin D is the best clinical indicator of
      vitamin D status. For many years, emphasis has been on measuring total levels of
      25-hydroxyvitamin D [25(OH)D], but recently, interest in measuring free 25(OH)D
      as a potentially better marker of vitamin D status has arisen. Since the 1980s
      when the first measurements of free 25(OH)D were made, little progress has been
      made in the development of rapid, reliable methods to determine the levels of
      free 25(OH)D. For many years, assessment of free 25(OH)D relied on calculations
      using levels of total 25(OH)D, albumin, and vitamin D binding protein (VDBP), for
      which many assays exist. However, because of vagaries in the measurement of VDBP
      in particular and the assumption of a constant affinity of VDBP for the vitamin D
      metabolites (which has been shown to be problematic), calculated values have
      proved suspect. This changed a few years ago when a new immunoassay was developed
      to measure free 25(OH)D directly. This review examines methods for determining
      free 25(OH)D, the different methods used in clinical studies, and the
      relationships between free 25(OH)D and other vitamin D metabolites and the
      physiologic functions affected by vitamin D metabolites, such as bone cell
      activity and turnover. The review also comments on the value of assessing free
      25(OH)D and the efforts to standardize the assays.

PMID- 28492134
TI  - Simplified 25-Hydroxyvitamin D Standardization and Optimization in Dried Blood
      Spots by LC-MS/MS.
AB  - Previous studies have assessed vitamin D status based on the 25-hydroxyvitamin D
      [25(OH)D] concentration measured in samples from dried blood spots (DBSs). In 40
      individuals participating in a clinical study, we compared 25(OH)D levels
      measured from DBSs and in serum using an LC-MS/MS reference procedure in
      collaboration with the Vitamin D Standardization Program. The main objective was
      to simplify and optimize current methods to produce an assay that can be used as
      a screening tool for 25(OH)D concentration assessment without derivatization. The
      DBS 25(OH)D levels, compared to serum concentrations, were found to have 101%
      accuracy overall, and the correlation coefficient (r) was 0.83 (P < 0.0001), with
      a significant linear relationship. Free 25(OH)D and vitamin D binding protein
      (VDBP) were assessed in the serum samples for potential correlations to the DBS
      calculations: the levels of free 25(OH)D had moderate to strong correlation to
      DBS and serum concentrations, with r values of 0.67 (P < 0.0001) and 0.76 (P <
      0.0001), respectively. VDBP and hematocrit had no significant correlation to
      either DBS or serum sample types, with r values <0.1. In conclusion, the use of
      two DBSs and an increase in DBS sample size improved overall sample
      representation without the need for derivatization, and produced an accurate and
      robust method that can be used to screen 25(OH)D levels.

PMID- 28492135
TI  - Ions in Wine and Their Relation to Electrical Conductivity Under Ultrasound
      Irradiation.
AB  - Change in electrical conductivity is considered a potential indicator for the on
      line monitoring of wine aging accelerated by ultrasound, as determined in our
      previous study; however, the exact mechanism of change is currently unclear. In
      this study, the ion content and the total ionic strength were analyzed by ion
      exchange chromatography to investigate the change mechanism of the electrical
      conductivity of wine under ultrasound irradiation. The results indicate that the
      changes in wine electrical conductivity during ultrasound treatment correlate
      with the changes in the cations (Na+, K+, Ca2+, Mg2+, and NH4+) and in the anions
      from the organic acids (malic acid, citric acid, tartaric acid, oxalic acid, and
      formic acid) and inorganic acids (Cl-, SO42-, and PO43-), especially for the
      ionic strength of the wine. Overall, electrical conductivity may be used to
      reflect the chemical reactions related to wine aging to a certain extent because
      the reactions can be initiated by the conversion of cations and by the
      degradation or auxiliary function of organic acids.

PMID- 28492136
TI  - Inhibition of ERK1/2 Signaling Impairs the Promoting Effects of TGF-beta1 on
      Hepatocellular Carcinoma Cell Invasion and Epithelial-Mesenchymal Transition.
AB  - Transforming growth factor-beta (TGF-beta) and ERK signaling have been implicated
      in various human cancers including hepatocellular carcinoma, but the underlying
      mechanism remains largely unclear. In this study, we aimed to explore the role of
      ERK1/2 in the regulation of TGF-beta's promoting and suppressive activities in
      HCC cells. Our data showed that treatment with TGF-beta1 enhanced invasion and
      epithelial-mesenchymal transition (EMT) in HCC HepG2 cells, accompanied with
      increased MMP9 production and activation of Smad2/3 and ERK1/2, but inhibited
      tumor cell proliferation. These effects were eliminated by treatment with
      SB431542, a TGF-beta inhibitor. Afterward, treatment with the MEK1/2 inhibitor
      U0126 reduced the TGF-beta1-induced invasion and vimentin and MMP9 secretion in
      HepG2 cells, without affecting the inhibitory effects of TGF-beta1 on HepG2 cell
      proliferation. Moreover, inhibition of Smad2/3 expression attenuated TGF-beta1
      induced cell invasion, ERK1/2 phosphorylation, and MMP9 production in HepG2
      cells. However, knockdown of Slug only reduced cell invasion but did not affect
      ERK1/2 activation and MMP9 secretion in HepG2 cells. These data indicate that TGF
      beta1 activates ERK1/2 in HepG2 cells through the Smad2/3 pathway but not the
      Slug pathway. In summary, our study demonstrates that inhibition of ERK1/2
      signaling attenuates the promoting effects of TGF-beta1 on the metastatic
      phenotypes of HCC cells without affecting its suppressive effects on HCC cell
      proliferation. Therefore, we suggest that ERK1/2 may be used as a molecular
      target for the treatment of TGF-beta-responsive HCC.

PMID- 28492137
TI  - The Importance of 25-Hydroxyvitamin D Assay Standardization and the Vitamin D
      Standardization Program.

PMID- 28492139
TI  - Histone Demethylase JARID1B Is Overexpressed in Osteosarcoma and Upregulates
      Cyclin D1 Expression via Demethylation of H3K27me3.
AB  - JARID1B has been proven to be upregulated in many human malignancies and is
      correlated with tumor progression. However, its expression and clinical
      significance in osteosarcoma are still unclear. Thus, the aim of this study was
      to explore the effects of JARID1B in osteosarcoma tumorigenesis and development.
      In this study, we found that the expression levels of JARID1B in osteosarcoma
      tissues were significantly higher than those in corresponding noncancerous bone
      tissues. In addition, JARID1B upregulation occurred more frequently in
      osteosarcoma specimens from patients with a poor prognosis. After JARID1B
      transfection in osteosarcoma cells, cell proliferation was significantly promoted
      in vitro and in vivo. On the contrary, knockdown of JARID1B inhibited cell
      proliferation in vitro and tumor growth in vivo. JARID1B can also decrease the
      G0/G1 phase cell numbers and increase the S and G2/M phase cell numbers. We
      further demonstrated that JARID1B regulates cyclin D1 expression through
      H3K27me3. These findings indicate that JARID1B may act not only as a novel
      diagnostic and prognostic marker but also as a potential target for molecular
      therapy in osteosarcoma.

PMID- 28492138
TI  - Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of
      Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway.
AB  - Prostate cancer has become the most commonly diagnosed and the second leading
      cause of cancer-related deaths in males. The long noncoding RNA second chromosome
      locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in
      a subset of prostate cancer. However, the significance and mechanism of SChLAP1
      in prostate cancer are not well known. In this study, we explored the role of
      SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of
      SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1
      expression was significantly increased in prostate cancer cells and tissues.
      Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and
      invasion in vitro and in vivo. In addition, a potential bonding site between miR
      198 and SChLAP1 was predicted, and a low expression of miR-198 was found in
      prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased
      the expression of miR-198, and SChLAP1 overexpression markedly decreased it,
      indicating that SChLAP1 acted as a negative regulator in the expression of miR
      198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and
      subsequently modulated the MAPK1 signaling pathway in prostate cancer. In
      conclusion, our study has identified a novel pathway through which SChLAP1 exerts
      its oncogenic role in prostate cancer at the level of miRNAs and provided a
      molecular basis for potential applications of SChLAP1 in the prognosis and
      treatment of prostate cancer.

PMID- 28492140
TI  - High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in
      Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium.
AB  - The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D
      [(25(OH)D] level <50 nM, is unclear. Intramuscular (IM) injection of a large
      bolus of vitamin D (>=100 000 IU) is used, but its safety is uncertain. In 10
      adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and
      at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3, 25(OH)D3,
      25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3
      [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS) assay; serum levels
      of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone
      metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks.
      All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels
      increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean +/- SEM
      of 126 +/- 7.9 nM (immunoassay) and 100 +/- 5.5 nM (LC-MS/MS)] but generally
      remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine.
      Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized
      calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but
      remained within the clinically normal range. Other biochemical parameters,
      including other vitamin D metabolites, plasma alkaline phosphatase, and
      parathyroid hormone levels, were unchanged. IM injection of a large bolus of
      vitamin D effectively increases serum 25(OH)D levels without evidence of
      metabolic abnormality.

PMID- 28492141
TI  - Procaine Inhibits the Proliferation and Migration of Colon Cancer Cells Through
      Inactivation of the ERK/MAPK/FAK Pathways by Regulation of RhoA.
AB  - Colon cancer is one of the most lethal varieties of cancer. Chemotherapy remains
      as one of the principal treatment approaches for colon cancer. The anticancer
      activity of procaine (PCA), which is a local anesthetic drug, has been explored
      in different studies. In our study, we aimed to explore the anticancer effect of
      PCA on colon cancer and its underlying mechanism. The results showed that PCA
      significantly inhibited cell viability, increased the percentage of apoptotic
      cells, and decreased the expression level of RhoA in HCT116 cells in a dose
      dependent manner (p < 0.05 or p < 0.01). Moreover, PCA increased the proportion
      of HCT116 cells in the G1 phase as well as downregulated cyclin D1 and cyclin E
      expressions (p < 0.05). In addition, we found that PCA remarkably inhibited cell
      migration in HCT116 cells (p < 0.01). However, all these effects of PCA on cell
      proliferation, apoptosis, and migration were significantly reversed by PCA + pc
      RhoA (p < 0.05 or p < 0.01). PCA also significantly decreased the levels of p
      ERK, p-p38MAPK, and p-FAK, but PCA + pc-RhoA rescued these effects. Furthermore,
      the ERK inhibitor (PD098059), p38MAPK inhibitor (SB203580), and FAK inhibitor
      (Y15) reversed these results. These data indicate that PCA inhibited cell
      proliferation and migration but promoted apoptosis as well as inactivated the
      ERK/MAPK/FAK pathways by regulation of RhoA in HCT116 cells.

PMID- 28492142
TI  - Technical Note: Determination of Cholecalciferol (Vitamin D3) in Standard
      Reference Material 3532 Calcium-Containing Solid Oral Dosage Form.
AB  - Vitamin D is an important nutrient for many areas of human health and well-being,
      including improved bone strength, muscle movement, cognitive function, and immune
      health. The National Institute of Standards and Technology, in collaboration with
      the National Institutes of Health Office of Dietary Supplements, has developed
      SRM 3532 Calcium-Containing Solid Oral Dosage Form to help address the analytical
      challenges seen by the dietary supplement communities for the determination of
      vitamin D3 (cholecalciferol) and elements. Described here is the process to
      assess the homogeneity and stability of the material, as well as the value
      assignment of the vitamin D3 levels.

PMID- 28492143
TI  - A Direct Assay for Measuring Free 25-Hydroxyvitamin D.
AB  - Recent studies suggest that the concentration and genotype of vitamin D binding
      protein (VDBP) are important factors that determine the bioavailability of 25
      hydroxyvitamin D [25(OH)D] in blood. Accumulating data indicate that, e.g., in
      pregnant women, hemodialysis patients, chronic kidney disease, liver failure, and
      bladder and pancreatic cancers, the measurement of free 25(OH)D in serum provides
      more relevant diagnostic information than measurement of total 25(OH)D. The aim
      of this study was to develop and validate an ELISA for direct measurement of free
      25(OH)D in serum. A simple and direct ELISA was developed, based on a two-step
      immunoassay procedure performed in a microtiter plate. The assay has been
      characterized in terms of precision (4-10% CV, according to concentration),
      sensitivity (limits of blank = 0.5-1.0 pg/mL and LODs = 1.3-1.8 pg/mL), accuracy
      (correlation to dialysis, ELISA = 0.99xdialysis-0.5 pg/mL, r2 = 0.74), cross
      reactivity of the antibody for the D2 form (77%), and addition of both VDBP and
      albumin (35-38% recovery upon addition of VDBP, 53-58% upon addition of albumin).
      The assay has already been used in multiple studies, including its comparison
      with calculation methods and in studies of patients with liver failure, different
      ethnic groups, supplemented mice, respiratory diseases, and obesity. The free
      25(OH)D ELISA can be used in studies as a valuable tool to establish the clinical
      relevance of free 25(OH)D.

PMID- 28492144
TI  - Clinical, Research, and Public Health Implications of Poor Measurement of Vitamin
      D Status.
AB  - There is widespread concern about the high prevalence of vitamin D deficiency
      amid evidence to support that such a state may increase the risk of a wide range
      of adverse health outcomes. Estimating the prevalence of deficiency, as well as
      establishing links to health outcomes, requires the accurate and precise
      measurement of 25-hydroxyvitamin D [25(OH)D] in serum or plasma. Accurate
      measurement of 25(OH)D underlies the definitions of vitamin D deficiency,
      insufficiency, and sufficiency and, thus, prevalence estimates. Imprecise
      measurement of 25(OH)D in epidemiological research can result in incorrect null
      findings of associations with disease. When associations with disease are found,
      the inaccuracy of measurement forestalls defining the absolute level of 25(OH)D
      that is associated with increased risk. For the clinician, both inaccuracy and
      imprecision are problematic, because clinical care is most often based on a
      single measurement to define vitamin D status. New initiatives to develop a
      standard reference method and the assignment of "true" values to samples provide
      a solution to these problems. The use of standardized assays in large population
      studies will allow comparisons to be made between populations and over time that
      have not previously been possible and will improve our understanding of the role
      of vitamin D in health and disease.

PMID- 28492145
TI  - Nuclear Medicine Imaging in Emergency Room and Priority Clinical Decision Making.

PMID- 28492146
TI  - Vitamin D Deficiency in Alopecia Areata.
AB  - OBJECTIVE: To compare the mean Vitamin D level in patients with alopecia areata
      (AA) with age and gender controlled matched healthy controls. STUDY DESIGN: Case
      control study. PLACE AND DURATION OF STUDY: Dermatology OPD, JPMC, from October
      2014 to March 2015. METHODOLOGY: All the patients diagnosed of alopecia areata by
      a trained dermatologist were selected. Controls were age and gender matched
      healthy volunteers. Venous blood was drawn and sent to hospital laboratory for 25
      (OH) vitamin D by enzyme immunoassay method on chemical analyser. Data was
      recorded on SPSS version 16. Mann-Whitney test was applied to compare vitamin D
      levels of cases and controls. P-value <0.05 was taken as significant. RESULTS:
      There are 30 cases of AA, and 30 age and gender matched controls. The mean age of
      our study group was 23.77 +/-8.86 ng/dL in patients and 24.03 +/-8.62 ng/dL in
      the control group. Fifteen (50%) patients presented between 3-12 months of onset
      of AA. Median (IQR) vitamin D level of cases was 13.5 (18.6) ng/dL and healthy
      controls was 22.5 (16.25) (p=0.001). CONCLUSION: Serum Vitamin D levels were
      significantly lower in patients with alopecia areata compared to healthy
      controls.

PMID- 28492147
TI  - Female Sexual Dysfunction in the Late Postpartum Period Among Women with Previous
      Gestational Diabetes Mellitus.
AB  - OBJECTIVE: To compare the status of female sexual dysfunction (FSD) between women
      with a history of previous gestational diabetes mellitus (GDM) and those with
      follow-up of a healthy pregnancy, using the female sexual function index (FSFI)
      questionnaire. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY:
      Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Training and
      Research Hospital, Istanbul, Turkey, from September to December 2015.
      METHODOLOGY: Healthy sexually active adult parous females were included.
      Participants were asked to complete the validated Turkish versions of the FSFI
      and Hospital Anxiety and Depression Scale (HADS) questionnaires. Student's t-test
      was used for two-group comparisons of normally distributed variables and
      quantitative data. Mann-Whitney U-test was used for two-group comparisons of non
      normally distributed variables. Pearson's chi-squared test, the Fisher
      FreemanHalton test, Fisher's exact test, and Yates' continuity correction test
      were used for comparison of qualitative data. RESULTS: The mean FSFI scores of
      the 179 participants was 23.50 +/-3.94. FSFI scores and scores of desire,
      arousal, lubrication, orgasm, satisfaction, and pain were not statistically
      significantly different (p>0.05), according to a history of GDM and types of FSD
      (none, mild, severe). HADS scores and anxiety and depression types did not
      statistically significantly differ according to the history of GDM (p>0.05).
      CONCLUSION: An association could not be found in FSFI scores between participants
      with both the history of previous GDM and with healthy pregnancy; subclinical
      sexual dysfunction may be observed in the late postpartum period among women with
      a history of previous GDM. This may adversely affect their sexual health.

PMID- 28492148
TI  - Immunohistochemical Expression of Epidermal Growth Factor Receptor in Head and
      Neck Squamous Cell Carcinoma.
AB  - OBJECTIVE: To determine the frequency of expression of epidermal growth factor
      receptor (EGFR) by immunohistochemistry in head and neck squamous cell carcinoma
      (HNSCC). STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Armed
      Forces Institute of Pathology (AFIP), Rawalpindi, from September 2015 to March
      2016. METHODOLOGY: Fifty-two cases of head and neck squamous cell carcinoma
      diagnosed on H&E stain were included in the study. Patients' gender and age were
      noted. Immunohistochemistry for EGFR was applied and the results were recorded.
      The data were analyzed by using computer software program SPSS version 19.
      Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out
      of the 52 patients of HNSCC, 37 patients were males and 15 females. The age of
      the patients was between 21 and 80 years with an average age of 58.58 +/-12.63.
      Out of 52 cases, 45 cases (86.53%) were positive for EGFR while 7 cases (13.46%)
      were negative for EGFR. Significant statistical association was not seen between
      the tumour grade and EGFR expression (p=0.162). CONCLUSION: The high expression
      of EGFR in head and neck cancers among Pakistani patients suggests its value as a
      therapeutic target. EGFR inhibitors have become well-known part of HNSCC
      treatment; therefore, patients with EGFR positive HNSCC can be benefitted from
      the therapy.

PMID- 28492149
TI  - The Histopathological Parameters Affecting Biochemical Recurrence in Radical
      Prostatectomies.
AB  - OBJECTIVE: To determine the relationship between biochemical recurrence and other
      histopathological factors in prostate cancer. STUDY DESIGN: Analytical study.
      PLACE AND DURATION OF STUDY: Pathology and Urology Departments, Izmir Ataturk
      Training and Research Hospital, between 2001 - 2013. METHODOLOGY: 117 cases
      diagnosed with prostatic adenocarcinoma and treated by radical prostatectomy were
      reviewed retrospectively for histopathological features; whereas, other
      prognostic findings were noted. PSA levels and many other histopathological
      parameters were assessed in order to put forth their effect on biochemical
      recurrence. RESULTS: PSA level (p<0.001), tumor volume (p<0.001), Gleason score
      (p<0.001), extraprostatic extension (p<0.001), perineural invasion (p<0.001),
      ganglion involvement (p=0.040), vascular invasion (p<0.001), positive surgical
      margins (p<0.001), presence of tertiary pattern (p=0.004) and the involvement of
      the seminal vesicles (p<0.001) were found to be statistically related to the
      pathological stage. Age, perineural invasion, high grade tertiary pattern,
      intraluminal mucin, collagenous micronodules and foamy cytoplasmic changes were
      unrelated to recurrence. CONCLUSION: Histopathological features can be helpful in
      predicting prognosis in prostatic adenocarcinomas. However some of the
      histopathological factors such as intraluminal mucin and foamy cytoplasmic
      changes may not reflect high recurrence.

PMID- 28492150
TI  - Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani
      Children.
AB  - OBJECTIVE: To determine the frequency of organic acidurais (OA) and amino
      acidopathies (AA) in selected high-risk patients screened in two years. STUDY
      DESIGN: Retrospective Observational study. PLACE AND DURATION OF STUDY: The Aga
      Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014.
      METHODOLOGY: Patients with OA and AA were included in the study and patients with
      IMDs other than OA and AA were excluded. Amino acids and organic acids were
      analyzed on high performance liquid chromatography and gas chromatography-mass
      spectrometry respectively. Clinical data and chromatograms of patients screened
      for IMDs were reviewed by chemical pathologist and metabolic physician. RESULTS:
      Eighty-eight cases (4.7%) were diagnosed including 41 OA (46.5%), 28 AA (31.8%)
      and 19 others (21.5%) from 1,866 specimens analyzed. Median age of the patients
      was 1.1 years, with high consanguinity rate (64.8%). Among OA, methyl CoA mutase
      deficiency was diagnosed in 9 (10.2%) and was suspected in 2 (2.3%) cases. Five
      (5.7%) cases of MHBD (2-methyl-3-hydroxybutyryl-CoA), 4 (4.5%) each of PPA
      (propionic aciduria) and HMG-CoA lyase deficiency, 3 (3.4%) cases each of IVA
      (isovaleric aciduria), multiple carboxylase deficiency, fructose-1, 6
      biphosphatase deficiency, fumarase deficiency, GA-1 (glutaric aciduria type 1)
      and 2 (2.3%) cases of EMA (ethyl-malonic aciduria). AA included 8 (9.1%) cases of
      MSUD (maple syrup urine disease), 6 (6.8%) cases of CBS (cystathionine beta
      synthetase) and UCDs (urea cycle disorders) each, 5 (5.7%) cases of
      hyperphenylalaninemia and 3 (3.4%) cases of hyperprolinemia were reported. Other
      inherited metabolic disorders included: 9 (10.2%) cases of intracellular
      cobalamin defects, 2 (2.3%) cases each of alkaptonuria, Canavan's disease, SUCL
      (succinate CoA ligase) deficiency, and 1 (1.1%) case each of DPD
      (dihydropyrimidine) deficiency, GA-2, NKH (non-ketotic hyperglycinemia), AADC
      (aromatic amino acid decarboxylase) deficiency. CONCLUSION: This study presents
      frequency of OA and AA in the high-risk Pakistani pediatric population analyzed
      locally.

PMID- 28492151
TI  - Secretagogin (SCGN) Plasma Levels and their Association with Cognitive and Social
      Behavior in Children with Autism Spectrum Disorder ASD).
AB  - OBJECTIVE: To investigate the secretagogin (SCGN) plasma levels in children with
      autism spectrum disorder (ASD) compared to age and gender-matched healthy
      control, and its association with cognitive and social behaviors by using
      childhood autism rating scale (CARS) and social responsiveness scale (SRS). STUDY
      DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and
      Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology,
      Faculty of Medicine, King Khalid University Hospital, King Saud University,
      Riyadh, Saudi Arabia, from October 2015 to May 2016. METHODOLOGY: SCGN levels
      were determined in the plasma of thirty-seven (37) autistic children using enzyme
      linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as
      indicated by their CARS scores and compared with thirty (30) age and gender
      matched control samples. Correlation between SCGN levels and different cognitive
      and social behavior scales (CARS and SRS) was determined by Spearman's
      correlation coefficient (r). RESULTS: The results indicated that autistic
      children (n=37) had significantly (p= 0.005) lower plasma level of SCGN {45.7
      (26.2) ng/ml [median (IQR)]} than those of healthy controls {n=30, 70.8 (48.6)
      ng/ml [median (IQR)]}. Children with severe (n=28, 76%) as well as mild to
      moderate autism (n=09, 24%) also exhibited significantly lower SCGN levels {47.5
      (27) ng/ml [median (IQR)], p =0.014} and {45.7 (16.6) ng/ml [median (IQR)], p =
      0.02)}, respectively than healthy controls {n=30, 70.8 (48.6) ng/ml [median
      (IQR)]}. However, there was no significant difference between the SCGN levels of
      children with mild to moderate and severe autism (p = 0.66). Spearman's
      correlation coefficient (r) was used to determine the relationships between SCGN
      levels and different variables (CARS, SRS). However, the results showed no
      significant correlation between SCGN and these scales. (CARS, r=-0.03, p=0.86;
      SRS, r=0.21, p=0.20). CONCLUSION: The low SCGN plasma levels in children with ASD
      probably indicate that SCGN might be implicated in the pathogenesis of autism.
      However, these data should be treated with caution until further investigations
      are performed using larger sample sizes to determine whether the decrease in
      plasma SCGN levels is a mere consequence of autism or it plays a pathogenic role
      in the disease.

PMID- 28492152
TI  - Effect of Stone Composition on the Outcomes of Semi-Rigid Ureteroscopy Using
      Holmium: Yttrium-Aluminum-Garnet Laser or Pneumatic Lithotripsy.
AB  - OBJECTIVE: To compare the effectiveness of laser lithotripsy (LL) and pneumatic
      lithotripters (PL) in calcium oxalate (CaOx) and calcium phosphate (CaP) stones
      and assess whether these stone compositions affect the outcomes of LL and PL.
      STUDY DESIGN: Comparative, descriptive study. PLACE AND DURATION OF STUDY:
      Istanbul Training and Research Hospital, Turkey, from August 2010 to August 2015.
      METHODOLOGY: A total of 114 patients underwent ureteroscopy using LL and PL.
      Fifty-eight (50.9%) had CaOx stones and 56 (49.1%) had CaP stones. The
      lithotripters were compared in stone composition groups, and stone compositions
      were compared in lithotripter groups. Patient characteristics, perioperative
      parameters, and postoperative complications were compared. RESULTS: The baseline
      patient and stone characteristics were similar in all groups. The operation time
      of the PL and LL for the patients with CaP stones (68.75 +/-32.88 and 44.48 +/
      34.37 minutes, respectively) was significantly shorter than the operation time of
      the PL and LL for the patients with CaOx stones (91.56 +/-30.54 and 65.75 +/
      37.74 minutes, (p=0.012 and p=0.009, respectively). Moreover, the patients with
      CaOx or CaP treated with LL 65.75+/-37.74 and 44.48 +/-34.37 minutes,
      respectively) had significant shorter operation time than the PL (91.56 +/-30.54
      and 68.75 +/-32.88 minutes, (p=0.046 and p=0.01, respectively). Stone-free rates
      were similar in all groups. The PL for the patients with CaP stones caused more
      postoperative fever and infection than the other groups (p=0.050). CONCLUSION:
      Though both PL and LL are effective in the treatment of CaOx and CaP stones, LL
      had a significantly shorter operation and hospitalization time and complication
      rates in patients with CaOx and CaP stones. So LL is a more feasible and safer
      modality in the treatment of recurrent CaP stones.

PMID- 28492153
TI  - Prognostic Value of p53 Expression Intensity in Urothelial Cancers.
AB  - OBJECTIVE: To determine association of immunohistochemical expression intensity
      of p53 with grade and stage of urothelial cancers. STUDY DESIGN: Descriptive
      cross-sectional analytical study. PLACE AND DURATION OF STUDY: Pathology
      Department, King Edward Medical University, Lahore, from January to December
      2016. METHODOLOGY: Data of transurethral resection/radical cystesctomy urinary
      bladder biopsies was collected. Clinical, radiological and cystoscopic findings
      of patients were noted from patients' charts in the Urology Ward. Biopsies were
      graded histologically according to WHO 2004 grading system. TNM system was used
      for pathological staging. On selected slides, immunoshistochemistry for p53 was
      applied. Nuclear immunoreactivity was considered positive if present in >10% of
      tumor cells and negative if <10% of tumor cells. Intensity was considered weak
      (less than 15% cells) and strong (more than 15% cells). Data was analyzed by SPSS
      version 21. Linear-by-linear association was calculated between p53 expression
      and stage of urothelial tumors, Chi-Square test was used to see association
      between grade and intensity of p53. Qualitative variables, like grade and stage
      of carcinoma along with p53 expression, were calculated in terms of frequencies
      and percentages. P <= 0.05 was taken as significant. RESULTS: Out of the 70
      patients, 61 (87%) were males and 9 (13%) females. Out of 25 low grade lesions, 4
      (16%) cases were p53 positive; and out of 45 high grade lesions, 41 (91%) cases
      were p53 positive. There was 33% (2/6 cases) positivity in Tis, 55% (16/29 cases)
      in T1, 72% in T2 (21/29), and 100% in T3a (5/5 cases) and T3b (1/1 case). Strong
      intensity of p53 staining was noted to be 5.4% (n=25) of low grade and 94.6%
      (n=45) of high grade tumors. CONCLUSION: p53 expression was greater and more
      frequently strong in higher grade and stage of urothelial carcinoma. It can be
      used as a prognostic marker in predicting higher grade and stage of bladder
      cancer.

PMID- 28492154
TI  - The Efficacy and Safety of Iodine-125 Brachytherapy Combined with Chemotherapy in
      Treatment of Advanced Lung Cancer: A Meta-Analysis.
AB  - The aim of this study was to systematically review the efficacy and safety of
      iodine-125 brachytherapy combined with chemotherapy in patients with advanced
      lung cancer. PubMed, MEDLINE, EBSCO, FMJS and Web of Science were searched to
      obtain randomized controlled trials (RCTs), published in English and Chinese,
      until February 2016. The evaluating indicators were complete response (CR),
      partial response (PR), stable disease (SD), progressive disease (PD), overall
      response rate (ORR), disease control rate (DCR), one-year overall survival, two
      year overall survival and adverse events. Revman 5.2 software was used for data
      syntheses and analyses. A total of 296 patients enrolled in 5 RCTs were
      ultimately included in this study based on our selection criteria, and 150
      patients received chemotherapy alone, while another 146 patients received the
      combination therapy of iodine-125 brachytherapy and chemotherapy. The results
      showed that iodine-125 brachytherapy combined with chemotherapy was superior to
      chemotherapy alone in CR (risk ratio [RR] = 3.66, 95% confidence interval [CI]:
      2.08 to 6.44, p<0.001), PR (RR = 1.47, 95% CI: 1.16 to 1.86, p=0.001), ORR (RR =
      1.85, 95% CI: 1.54 to 2.22, p<0.001), DCR (RR = 1.19, 95% CI: 1.10 to 1.29,
      p<0.001), one-year overall survival (RR = 1.46, 95% CI: 1.12 to 1.92, p=0.006)
      and PD (RR = 0.20, 95% CI: 0.09 to 0.43, p<0.001); meanwhile, there was no
      significant difference in two-year overall survival (RR = 1.30, 95% CI: 0.72 to
      2.37, p=0.39). In terms of adverse events, the combination therapy significantly
      increased the incidence of neumothorax (RR = 4.93, 95% CI: 1.94 to 12.55,
      p=<0.001); however, no significant differences were found in the incidence of
      other adverse events. This study indicated that the combination therapy of iodine
      125 brachytherapy and chemotherapy could improve the therapeutic efficacy of
      advanced lung cancer without increasing the incidence of adverse events, except
      pneumothorax.

PMID- 28492155
TI  - An Audit to Evaluate the Image Quality of Magnetic Resonance of Knee at Radiology
      Department of a Tertiary Care Hospital.
AB  - : light of recommendations of ACR. STUDY DESIGN: Aclinical audit. PLACE AND
      DURATION OF STUDY: Department of Radiology, Jinnah Hospital, Lahore, from August
      2015 to February 2016. METHODOLOGY: Scans of 20 patients who underwent MRI of
      knee in August 2015 were studied retrospectively to assess the quality of images
      obtained in the first audit. Based on the findings of this audit, recommendations
      were made and re audit was done 6 months later in February 2016 to look for
      improvement in local practice. RESULTS: In the first audit, images were acquired
      in all the three necessary planes and the sagittal and coronal images had
      appropriate slice thickness, interslice gap as well as adequate anatomical
      coverage in all the patients. However, FOV (field of view) was appropriately set
      in 66% of cases in axial plane, 5% in sagittal plane, and 0% in coronal plane.
      Also, the anatomical coverage was not upto the mark in axial plane with 13
      studies (66%) having adequate superior coverage, and 16 cases (80%) having
      recommended inferior anatomical coverage. The re audit performed 6 months later
      showed improvement with 100% compliance to standards. CONCLUSION: The first audit
      showed many shortcomings in acquiring of MRI data in patients undergoing knee MRI
      with FOV requiring a decrease in all planes and anatomical coverage increase in
      axial plane. These recommendations were made in departmental meetings and re
      audit was done after 6 months. This second audit showed 100 % compliance.

PMID- 28492156
TI  - Electrical Storm or Naxos Syndrome in an Adult Causing Recurrent Syncope.
AB  - Among the rare and well-known causes of sudden cardiac death by malignant
      arrthymias is a condition called arrhythmogenic right ventricular cardiomyopathy.
      It commonly presents with right ventricular dilatation, dysfunction and
      ventricular tachycardia of left bundle branch morphology due to fibro-fatty
      infiltration of right ventricle in second to fifth decade of life, making it an
      unrecognized and important cause of sudden cardiac death. Two rare variants of
      arrhythmogenic right ventricular cardiomyopathy are Carvajal syndrome and Naxos
      syndrome. Both variants have systemic manifestations. Being a rare variant of
      arrhythmogenic right ventricular dysplasia, Naxos syndrome was initially
      described in the families of the Greek island of Naxos. It is a recessive
      disorder with cardio-cutaneous manifestations characterized by arrhythmogenic
      right ventricular cardiomyopathy, palmoplantar keratoderma and wooly hair. We
      report a rare case of Naxos syndrome in an adult patient presented with recurrent
      episodes of palpitation and syncope.

PMID- 28492157
TI  - Angiomyxolipoma of Tongue.
AB  - Angiomyxolipoma is a rare histological variant of lipoma, characterized by
      proliferation of adipose tissue associated with a variable amount of myxoid
      stroma with numerous thick- and thin-walled blood vessels. An exhaustive
      literature review could reveal only 12 cases of angiomyxolipoma affecting
      subcutaneous tissue, subungual area and spermatic cord. In oral cavity, only 2
      cases of angiomyxolipoma have been reported to date, one case in the buccal
      mucosa and one case in the floor of the mouth. Hence, this is only the third case
      of angiomyxolipoma affecting oral cavity and the first case of angiomyxolipoma of
      the tongue. We report a case of a 51-year male presenting with a swelling on the
      right lateral border of the tongue. The lesion was excised and microscopical
      examination confirmed the diagnosis of angiomyxolipoma.

PMID- 28492158
TI  - Metachronous Metastatic Renal Cell Carcinoma to the Jejunum Presenting with
      Massive Lower Gastrointestinal Bleeding.
AB  - Metastatic renal cell carcinoma (MRCC) is a rare cause of massive lower
      gastrointestinal bleeding (LGIB). We report a 51-year man who underwent left
      nephrectomy for renal cell carcinoma (RCC) 6 years ago. presenting with massive
      LGIB. Preoperative abdominal computed tomography (CT) revealed small bowel mass.
      Exploration of the abdomen revealed jejunal mass. Resection of the mass along
      with the jejunal segment with end-to-end anastomosis was performed.
      Histopathology of the jejunal mass confirmed MRCC. MRCC should be expected as a
      source of massive LGIB in a patient with history of RCC. Surgical intervention
      should not be delayed in a hemodynamically unstable patient and persistent
      bleeding.

PMID- 28492159
TI  - Iloprost Instillation in Two Neonates with Pulmonary Hypertension.
AB  - Pulmonary hypertension may coexist with certain diseases in neonates. Iloprost
      inhalation is one of the treatments which cause selective pulmonary
      vasodilatation. Inhalation is not an easy way of drug administration in
      mechanically ventilated infants; as some exhibit desaturations during inhalation.
      Moreover, inhalation of drug requires cessation of mechanical ventilation, if
      patient is on high frequency oscillatory ventilation. We presented two patients
      with pulmonary hypertension; term baby with congenital diaphragmatic hernia and
      preterm baby with respiratory distress syndrome; who had iloprost instillation
      during mechanical ventilation treatment. Iloprost instillation was well tolerated
      with no side effects in the term patient with diaphragmatic hernia; whereas
      severe blood pressure fluctuations were observed in the preterm infant. This
      report may courage administration of iloprost in term neonates with resistant
      pulmonary hypertension.

PMID- 28492160
TI  - Very Late Stent Thrombosis: Is There Any Limit, When to Stop Antiplatelet
      Therapy?

PMID- 28492161
TI  - Cardiologist-Dentist Interaction in the Dental Management of Immunocompromised
      Cardiac Patient.

PMID- 28492162
TI  - Spuriously Low HbA1C Levels in a Type II Diabetes Patient Taking Dapsone.

PMID- 28492163
TI  - Antibiotic Resistance Pattern of Acinetobacter spp. Strains Isolated from Blood
      Infections in Shahid Sadoughi Hospital, Yazd, Iran.

PMID- 28492164
TI  - Ultrasound-Guided Vascular Access: An Evolving Standard of Care Clinical
      Practice, which is Extremely Under-Utilized in Pakistan.

PMID- 28492165
TI  - [The contribution of legal medicine in child protection: Presentation of a
      multidisciplinary approach].
AB  - INTRODUCTION: Maltreatment is a complex issue and therefore, requires a
      multidisciplinary approach, which has been commonly used in North America since
      the 1980s but remains unsystematic in France. Since 1999, the Centre d'Accueil en
      Urgence des Victimes d'Agression (emergency unit for victims of assault) of the
      Bordeaux University Hospital has brought together various medical, paramedical,
      and social actors on this issue. A standardized psychosocial assessment procedure
      has been introduced and is detailed in this paper, and was consistently conducted
      in all cases of suspicion of abuse on a minor. METHOD: The authors studied 74
      cases of minors having undergone a psychosocial assessment following suspicions
      of maltreatment between 1 July 2014 and 30 June 2015 that were not referred to
      the courts. RESULTS: Forty-five girls and 29 boys, mean age 7 years, claiming
      mainly (75 %) to have been subjected to sexual violence, were addressed to us by
      internal partners (n=15) and external partners (n=37) and 22 who came to our unit
      by self-referral. Following our assessment, 35 returned to their home and 36 went
      to court following a police complaint (n=17) and a report filed to the public
      prosecutor of the Republic (n=19). Three of these cases were subjected to a
      report on matters of concern sent to the departmental council. CONCLUSION: Given
      the absence of a national consensus on the methodology used for assessing
      suspicions of maltreatment on minors, our psychosocial assessment can facilitate
      the task with its peer review as well as the detection and judicialization of the
      maltreatment. The authors also highlight the recent modification of article 226
      14 of the Penal Code, which aims at protecting professionals reporting matters to
      legal authorities from any legal proceeding, except if it is established that the
      individual did not act in good faith.

PMID- 28492166
TI  - [Violence in schools: Prospective study conducted in an emergency reception
      center for victims of aggression].
AB  - INTRODUCTION: Although violence in schools is quite well conveyed in the media,
      the French literature data remain patchy, and the figures available arise mainly
      from surveys of victimization. This study had two main purposes: to add to the
      national epidemiological data on this phenomenon and to emphasize the actions
      that can be undertaken by the practitioner facing such events. MATERIAL AND
      METHODS: This was a prospective descriptive study that was conducted from
      September 1st, 2014, to June 30, 2015, in a single center, the CAUVA, an
      emergency center within the Bordeaux University Hospital for victims of assault.
      Included in the study was any person alleging acts of violence on the way to
      school, in the neighborhood, or within the school itself, and who was examined at
      the CAUVA following a judicial requisition. An anonymized questionnaire was
      distributed during the consultation. RESULTS: We collected 41 questionnaires over
      a 10-month period with 70.7% males (n=29) and 29.3% females (n=12), with a mean
      age of 14 years and 5 months (range, 7-49 years). The subjects included two
      teachers and 39 students. The time between the event and the forensic examination
      at CAUVA was mostly less than or equal to 7 days (n=18), between 7 and 15 days
      (n=14), 15 and 30 days (n=6), and more than 30 days (n=3). Twenty-six attacks
      (63%) took place inside the school - 21 middle schools - eight near the school,
      and seven between the student's home and the school. Inside the school, the
      events took place during a break (n=15), in the classroom (n=9), and during
      cultural outings (n=2). For one student out of two (n=25), the event reported was
      the first with acts of physical (n=37), psychological (n=20), or sexual violence
      (n=2). In 14.6% (n=6) of the cases, the assailant was a teacher and in almost 83%
      (n=34) of the cases it was another student, either from the same class (n=19) or
      another class (n=14), or a former student (n=1). CONCLUSION: This study brings
      out trends that can assist the practitioner during consultations related to
      violence. Screening, the description of the physical and psychological impact,
      and dispatching to a medical-legal unit for complex situations or sexual assaults
      contribute to making the general practitioner, the emergency physician, the
      pediatrician, and the school doctor key players in the treatment and management
      of violence.

PMID- 28492167
TI  - Management of cholestatic pruritus in children with Alagille syndrome: Case
      report and literature review.
AB  - Alagille syndrome causes intractable pruritus and disfiguring xanthomas because
      of retained bile acids and cholesterol. Drug therapy in addition to surgical
      intervention may be effective in many patients in reducing serum bile acids,
      cholesterol levels, pruritus, and skin xanthomas. In this report, we describe a
      child with Alagille syndrome who presented with severe pruritus and xanthomas as
      a consequence of severe hypercholesterolemia and discuss the treatment
      modalities.

PMID- 28492168
TI  - Accidental intravenous administration of paracetamol syrup in a child.
AB  - OBJECTIVE AND IMPORTANCE: Medication administration errors occur frequently in
      clinical practice. CLINICAL PRESENTATION: An 18-month-old child presented with
      vomiting and diarrhea. Due to a rise in temperature, paracetamol syrup was
      prescribed, but a nurse inadvertently administered the drug IV through the
      peripheral venous access. INTERVENTION: The child was referred to the pediatric
      intensive care unit where his clinical condition improved and the risk of
      peripheral venous and pulmonary embolism was excluded. CONCLUSION: The use of
      specific oral syringes should become a standard of practice in every healthcare
      organization and more supervision of new nurse graduates is necessary. Also,
      attention to the relationship with parents should be guaranteed because the
      communication of medical errors is a highly challenging aspect of these errors.

PMID- 28492169
TI  - [Learning disorders in ADHD: How are they related?]
AB  - Learning difficulties in general and learning disabilities in particular are
      almost constant in attention deficit disorder with or without hyperactivity
      (ADHD). Despite a major research effort, the extent and diversity of these
      comorbid events still raise many questions about the exact nature of their
      pathogenetic condition (simple consequences of ADHD or specific related
      disorders?) and consequently the best way to support them. This article aims to
      present a brief review of the current data.

PMID- 28492170
TI  - Reticulated acanthoma with sebaceous differentiation.

PMID- 28492171
TI  - Eight cases of cutaneous leishmaniasis due to Leishmania infantum with protean
      presentation.

PMID- 28492172
TI  - Fingernail involvement in adult Langerhans cell histiocytosis.

PMID- 28492173
TI  - Disease ecology of Hematodinium perezi in a high salinity estuary: investigating
      seasonal trends in environmental detection.
AB  - The blue crab Callinectes sapidus has seen a general decline in population
      levels. One factor influencing mortality is infections by Hematodinium perezi, a
      dinoflagellate parasite. A 2 yr study was conducted in 2014 and 2015 to monitor
      H. perezi DNA within the Maryland (USA) coastal bays, comparing seasonal cycles
      in the abundance of parasite DNA in environmental samples to parasite presence in
      host blue crabs. A late summer to early fall peak in H. perezi infections in blue
      crabs was observed, consistent with previous work. Infection intensities matched
      this trend, showing a slow progression of low intensity infections early in the
      year, with a peak in moderate and heavy infections occurring between July and
      September, for both years. It was hypothesized that the peak in water column
      occurrence would coincide with those months when infection intensities were
      highest in blue crabs. As the peaks in water column occurrence were in July 2014
      and August-September 2015, this is consistent with sporulation being the primary
      contributor to environmental detection in summer months. An additional peak in
      environmental detection occurred in both years during the early spring months,
      the cause of which is currently unknown but may be related to infections in
      overwintering crabs or alternate hosts. Several new crustacean hosts were
      identified within this estuary, including grass shrimp Palaemonetes spp. and the
      sand shrimp Crangon septemspinosa, as well as the mud crab Dyspanopeus sayi.
      Improved knowledge of this disease system will allow for better management of
      this important fishery.

PMID- 28492174
TI  - Hematodinium spp. infections in wild and cultured populations of marine
      crustaceans along the coast of China.
AB  - The parasitic dinoflagellate Hematodinium spp. infects a broad range of marine
      crustaceans. Its epidemics have impacted wild populations of various commercial
      fishery species around the world and the sustainability of mariculture in China.
      To study the epidemiology of Hematodinium spp. in marine crustaceans along the
      coast of China, we conducted a broad survey of wild and cultured stocks of major
      crustacean species in 2013 to 2015. Hematodinium sp. infections were identified
      in wild stocks of Portunus trituberculatus from Huludao, Laizhou, Qingdao,
      Yangtze River Estuary and Zhoushan, and Scylla paramamosain from Shantou; and
      cultured stocks of Portunus trituberculatus and Penaeus monodon from a
      polyculture pond in Qingdao. In the polyculture pond, Hematodinium sp. infections
      were observed in Portunus trituberculatus from June until October, with peak
      prevalence (up to 90%) observed in late July to early August. Furthermore,
      Hematodinium sp. infection was identified for the first time in the giant tiger
      prawn Penaeus monodon in the polyculture system during the disease outbreak.
      Phylogenetic analysis indicated that the Hematodinium isolate infecting Penaeus
      monodon was identical to the isolate infecting the co-cultured Portunus
      trituberculatus, and it was grouped into H. perezi genotype II together with the
      other isolates reported in China. The Hematodinium sp. isolated from Portunus
      trituberculatus appeared to have similar life stages as the H. perezi genotype
      III isolated from the American blue crab Callinectes sapidus. Our study indicates
      that outbreaks of Hematodinium disease can be a significant threat to the widely
      used polyculture system for decapods in China that may be particularly vulnerable
      to such generalist pathogens.

PMID- 28492175
TI  - Risk factors associated with white spot syndrome virus outbreaks in marine shrimp
      farms in Rayong Province, Thailand.
AB  - The purpose of this study was to determine risk factors for white spot disease
      (WSD) in Rayong, Thailand. A study was conducted from October 2014 to March 2015
      to identify potential farm-level risk factors using a validated questionnaire. We
      completed 1 questionnaire for each farm; a total of 38 questionnaires from the
      case farms and 127 questionnaires from the control farms were collected. The
      results showed that the presence of WSD in previous crops and the use of seawater
      were risk factors (p < 0.01), indicating that the environment plays an important
      role in WSD outbreaks in Rayong. Good management practices for pond preparation
      and other mitigation steps should be part of a control measure program for WSD in
      this region.

PMID- 28492176
TI  - Morphological re-description and phylogenetic relationship of five myxosporean
      species of the family Myxobolidae infecting Nile tilapia.
AB  - Freshwater fish have a major economic and nutritional importance worldwide.
      Myxosporeans are highly dangerous parasites that infect different fish species,
      causing severe damage to a large number of economically important species,
      especially in aquaculture. We conducted a survey of myxosporean parasites
      infecting Nile tilapia Oreochromis niloticus (Perciformes: Cichlidae) collected
      from different localities along the River Nile passing through Giza province,
      Egypt. Out of 100 fish specimens collected, 45 were found to be naturally
      infected with these parasites in the region of the trunk kidney. Light
      microscopic examination revealed the presence of 5 distinct myxosporean species
      belonging to 2 different genera, viz. Myxobolus and Triangula, belonging to the
      family Myxobolidae; all 5 species have been previously described. Morphological
      characteristics, host specificity and geographical distribution, tissue tropism,
      and molecular analysis of the partial sequence of small subunit ribosomal DNA
      gene revealed that the recovered myxosporean species described herein were
      genetically distinct from other myxozoan species but had 95% sequence similarity
      to M. cerebralis. Also, phylogenetic analysis placed the present myxosporean
      species in the freshwater Myxobolus clade, which is a sister group of freshwater
      Myxobolus/Henneguya species.

PMID- 28492177
TI  - Characterization of Aliivibrio fischeri strains associated with disease outbreak
      in brill Scophthalmus rhombus.
AB  - Three bacterial isolates were recovered from a disease outbreak with high
      mortality affecting brill Scophthalmus rhombus (Linnaeus, 1758). Moribund fish
      showed no external signs of disease, but plentiful haemorrhages were observed in
      liver. On the basis of phenotypic and genotypic characterization, the isolates
      were identified as Aliivibrio fischeri. The phenotypic profile of the isolates
      was basically similar to that of the type strain of this species, although some
      discrepancies were observed, mainly in the BIOLOG GN profile. The main cellular
      fatty acids of strain a591 were also consistent with this species. The highest
      16S rDNA sequence similarities were recorded with the type strain of A. fischeri
      (99.07%); other Aliivibrio species showed similarity values below 96%. The
      highest sequence similarities with gyrB, rpoD and recA genes were also recorded
      with A. fischeri type strain (99.31, 98.99 and 95.29% similarity, respectively).
      DNA-DNA hybridization assays confirmed that these isolates belong to A. fischeri;
      levels of DNA relatedness were 73.5 to 86.2% with isolate a591 (reciprocal values
      of 86.9 to 99.04%). Finally, a virulence evaluation of the isolates using
      Senegalese sole fry was also performed; significant mortalities (100% mortality
      within 5 d) were recorded by intraperitoneal injection, but only with high doses
      of bacteria (2 * 106 cfu g-1 body weight).

PMID- 28492178
TI  - Isolation of Bdellovibrio and like organisms and potential to reduce acute
      hepatopancreatic necrosis disease caused by Vibrio parahaemolyticus.
AB  - Acute hepatopancreatic necrosis disease, a severe disease of shrimp, is caused by
      Vibrio parahaemolyticus (AHPND Vp), a halophilic bacterium harboring a plasmid
      that contains toxin genes homologous to Photorhabdus insect-related toxins. We
      obtained 9 isolates of Bdellovibrio and like organisms (BALOs) from water and
      sediment samples in Thailand. Using 16S rRNA sequencing, all of the organisms
      were identified as Bacteriovorax spp. and were able to attack all tested AHPND Vp
      isolates. In addition, their various susceptible hosts, including Gram-positive
      and Gram-negative bacteria, were observed. The optimal ratio for interaction
      between the Bacteriovorax isolate BV-A and AHPND Vp was determined to be 1:10.
      The suitable conditions applied for co-culture between BV-A and AHPND Vp were 30
      degrees C, 2% NaCl, and pH 7.6. The capability of BV-A to reduce numbers of AHPND
      Vp in vitro was observed in co-culture after incubation for 2 d and continued
      until the end of the incubation period. In vivo, BV-A was able to reduce
      mortality of shrimp post-larvae infected with AHPND Vp. In addition, BV-A
      significantly decreased the formation of biofilm by AHPND Vp. These findings
      provide evidence for using Bacteriovorax as a biocontrol of AHPND Vp in shrimp
      aquaculture.

PMID- 28492179
TI  - Virulence variation among strains of the emerging infectious fungus
      Batrachochytrium dendrobatidis (Bd) in multiple amphibian host species.
AB  - Emerging infectious diseases have been documented in numerous plant and animal
      populations. The infectious disease amphibian chytridiomycosis, caused by the
      fungus Batrachochytrium dendrobatidis (Bd), is associated with global amphibian
      population declines. While much Bd-amphibian research has centered on response
      variation in hosts, a paucity of information exists on how variation in the
      pathogen, such as strain differences, affects infection dynamics. To examine how
      different Bd strains may differentially impact multiple hosts, we conducted
      laboratory experiments to measure 2 infection outcomes, viz. host survival and
      pathogen load, in 3 amphibian host species (Pacific treefrog, western toad, and
      Cascades frog) after exposure to 3 different Bd strains (an additional fourth Bd
      strain was tested in toads only). Our results confirm that the infection response
      differs among host species. Western toads experienced significant mortality, but
      Pacific treefrogs and Cascades frogs did not. Interestingly, our experiment also
      captured strain-dependent virulence variation but only in 1 host species, the
      western toad. Increased mortality was observed in 2 of the 4 Bd strains tested in
      this host species. Toads were also the only host species found to have variable
      pathogen load dependent on strain type; individuals exposed to the Panama strain
      harbored significantly higher loads compared to all other strains. These findings
      underscore the dynamic nature of Bd infection, showing that virulence can vary
      contingent on host and strain type. We highlight the importance of both host- and
      pathogen-dependent factors in determining overall infection virulence and show
      the need for in vivo testing to fully assess pathogenicity.

PMID- 28492180
TI  - Batrachochytrium dendrobatidis is present in Poland and associated with reduced
      fitness in wild populations of Pelophylax lessonae.
AB  - The fungus Batrachochytrium dendrobatidis (Bd) is a pathogen associated with
      global declines of amphibians. We used qPCR to detect Bd in 255 samples from 10
      Polish populations of 8 species. We found Bd infection in 3 species (Bombina
      variegata, Pelophylax lessonae, P. esculentus). The infection intensity in P.
      lessonae reached a maximum of 58400 genomic equivalents of zoospores (GE), and
      the 2 most heavily infected individuals died. Previous observations of the
      populations that included infected individuals showed reduced body size, failure
      to reproduce, and mortalities of adults. These data highlight the importance of
      emerging diseases, and the need to recognize them as an important factor in
      conservation of the genus Pelophylax in Poland and Central and Eastern Europe.

PMID- 28492181
TI  - Coinfection by Streptococcus phocae and cetacean morbillivirus in a short-beaked
      common dolphin Delphinus delphis.
AB  - We describe gross, histopathological, and immunohistochemical features of
      Streptococcus phocae and cetacean morbillivirus coinfection in a short-beaked
      common dolphin Delphinus delphis. Major gross findings were cutaneous purulent
      nodules in the tail fluke, vegetative mitral valve endocarditis, and presumed
      postpartum pyometra. Histologic examination revealed bacterial septicemia
      characterized by widespread intravascular coccoid bacterial emboli. These were
      associated with fibrinonecrotizing to pyogranulomatous dermatitis and
      panniculitis, embolic pneumonia, neutrophilic and lymphoplasmacytic
      meningochoroiditis, random neutrophilic hepatitis, lymphoplasmacytic myocarditis
      and epicarditis, necrotizing adrenalitis, suppurative endometritis, and
      multicentric reactive lymphadenopathy. Bacteriology and molecular analysis with
      sequencing of the 16S rRNA gene identified S. phocae from lung, brain, and
      adrenal gland tissue. Immunohistochemical analysis for morbillivirus detection
      revealed positive immunolabeling in the epithelium of the choroid plexus of the
      fourth ventricle. Published reports on S. phocae infection in cetaceans are rare,
      and pathological details are limited. The present case indicates that S. phocae
      has potential pathogenic capacity in common dolphins. The pathogenesis is
      proposed to have involved cutaneous penetration after a skin trauma, leading to
      initial cutaneous disease and eventual systemic infection.

PMID- 28492182
TI  - Hexagonal boron nitride: a promising substrate for graphene with high heat
      dissipation.
AB  - Supported graphene on a standard SiO2 substrate exhibits unsatisfactory heat
      dissipation performance that is far inferior to the intrinsic ultrahigh thermal
      conductivity of a suspended sample. A suitable substrate for enhancing thermal
      transport in supported graphene is highly desirable for the development of
      graphene devices for thermal management. By using molecular dynamics simulations,
      here we demonstrate that bulk hexagonal boron nitride (h-BN) is a more appealing
      substrate to achieve high performance heat dissipation in supported graphene.
      Notable length dependence and high thermal conductivity are observed in h-BN
      supported single-layer graphene (SLG), suggesting that the thermal transport
      characteristics are close to that of suspended SLG. At room temperature, the
      thermal conductivity of h-BN-supported SLG is as high as 1347.3 +/- 20.5 Wm-1 K
      1, which is about 77% of that for the suspended case, and is more than twice that
      of the SiO2-supported SLG. Furthermore, we find that the smooth and atomically
      flat h-BN substrate gives rise to a regular and weak stress distribution in
      graphene, resulting in a less affected phonon relaxation time and dominant phonon
      mean free path. We also find that stacking and rotation significantly impacts the
      thermal transport in h-BN-supported graphene. Our study provides valuable
      insights towards the design of graphene devices on realistic substrate for high
      performance heat dissipation applications.

PMID- 28492183
TI  - Evaluation of [Formula: see text] enrichment values obtained with an oral breath
      test under conditions of impaired gastric functioning.
AB  - Gastric emptying can be assessed by an oral administration of a 13C labeled
      substrate and its response in the expiratory release of the oxidation product
      [Formula: see text]. Impaired gut function, reflected, for example, in an
      intolerance against enteral nutrition may delay or discontinue gastric emptying,
      potentially leading to multiple peaks in the time profile of expiration. The
      resulting profile cannot be analyzed by the usual data evaluation that is based
      on a 'beta exponential' (BEX) function. We developed a new approach that better
      reflects the underlying physiology. It allows a flexible time profile of gastric
      release and considers a transient [Formula: see text] retention in different
      compartments as well as an incomplete recovery of [Formula: see text] in the
      expiration. Parameters that describe the distribution/retention kinetics cannot
      be determined based on the same breath data that were used to estimate emptying.
      To enable the determination of the kinetic parameters, they were constrained to
      match published data using a Bayesian statistical analysis. The applicability of
      the new model was compared with BEX for healthy subjects. BEX fails to explain
      the observed data and, compared to the new approach, overestimates the speed of
      emptying. Predictive accuracy under impaired gastric motility was explored using
      synthetic data. Only the new approach can reproduce a multiphase absorption
      profile. When routine benchtop equipment was used for measurements, then the rate
      limiting step for precision in the estimate of emptying is the quality in the a
      priori estimate for kinetic parameters rather than precision in measurements.
      Only about 80% of the absorbed [Formula: see text] has to be released by
      expiration. With these features, the new approach promises to widen the
      applicability of breath tests for gastric emptying.

PMID- 28492184
TI  - Thermal stability and optical properties of Si-Ge nanoparticles.
AB  - Silicon-germanium is an important alloy mainly used in thermoelectricity and
      electronics. However, its thermal and optical properties still need further
      investigation at the nanoscale. That is why in this study, the size and shape
      effect on the silicon-germanium phase diagram is investigated through the nano
      thermodynamics methodology. As expected, the phase diagram undergoes a shift down
      in temperature when the size decreases. However, it is demonstrated and explained
      why the size effect on the solidus-liquidus curves is much stronger than the one
      on the miscibility gap. Moreover, the shape effect is investigated for various
      faceted polyhedral nanoparticles as well as for the sphere. Phase maps are then
      provided as a function of the number of facets, at 4 and 10 nm, in order to
      determine the structure of the alloy. Furthermore, the size and shape effects on
      the energy bandgap are also studied. The energy bandgap increases when the size
      is reduced. The cube and tetrahedral shapes exhibit the largest size effect on
      the thermal and optical properties of the silicon-germanium alloy. Finally, this
      paper provides a useful roadmap for experimentalists willing to tune the
      properties of this alloy.

PMID- 28492185
TI  - Reconnoitring the peer review process....

PMID- 28492186
TI  - Recent research trends in dentistry.
AB  - Research being an investigative process is employed to increase or revise the
      current knowledge. Scientific research involves the conduct of a methodical study
      to prove a hypothesis or give an answer to a specific question with the main aim
      of finding definitive answer. This paper aims to advance knowledge of research
      and develop interest in the postgraduate students. It also throws light on the
      existing and emerging research strengths within a "high-performance culture." The
      trends in dental research worldwide are looked at, in particular, a comparison
      between the publication status in two countries, namely India and Australia. The
      current themes in dental research are also discussed to facilitate future
      projects for the aspiring pediatric dentists. Stress is given to the importance
      of evidence-based dentistry as the current times call for high-quality and
      ethical papers which are devoid of plagiarism. The common reasons for failure of
      a research are explored and the strengthening factors are highlighted. Proper
      planning of a pertinent research project is beneficial to the researcher as well
      as the dental community.

PMID- 28492187
TI  - Evaluation and association of serum iron and ferritin levels in children with
      dental caries.
AB  - BACKGROUND: Iron deficiency anemia accounts for 90% of all types of anemia in the
      world. Although the prevalence has declined in recent years, it remains an
      important pediatric public health problem. Iron deficiency has also been
      associated with dental caries. It impairs salivary gland function causing reduced
      salivary secretion and buffering capacity leading to increased caries activity.
      AIM: The aim of the study is to explore an association between dental caries and
      serum levels of iron and ferritin in children aged 3-12 years. Subjectsand
      Methods: The study group included 120 children, hospitalized for uncomplicated
      medical problems. Blood reports were evaluated to determine serum iron and
      ferritin levels. Dental caries experience was assessed using deft index.
      STATISTICAL ANALYSIS USED: The collected data were tabulated and analyzed using
      Student's t-test and Pearson's correlation coefficient. RESULTS: Out of 120
      children, 38 children showed low serum iron levels of which 31 children had
      dental caries and nine out of 15 children in the high serum iron level group
      showed dental caries. High ferritin levels were seen in three children among
      which two children were caries-free and only one child had a low ferritin level
      who also had a positive deft score. CONCLUSION: Based on the results, it was
      concluded that there is an inverse association between serum iron levels and
      dental caries whereas there is no association between serum ferritin levels and
      dental caries.

PMID- 28492188
TI  - Assessment of maternal risk indicators for the development of caries in their
      children: A comparative, cross-sectional study.
AB  - INTRODUCTION: Certain factors in mothers could be risk indicators for certain
      diseases in their children. Hence, this study was undertaken to assess maternal
      risk indicators for the development of early childhood caries in their children.
      METHODOLOGY: A comparative, cross-sectional study was designed among 180 mother
      child pairs attending various Anganwadi centers. Demographic, dietary, oral
      hygiene practices and other necessary information were collected from mothers
      using a structured questionnaire. Caries status and amount of plaque were
      recorded through clinical examination. Nonstimulated saliva from mothers was
      cultured for mutans streptococci (MS). Data were analyzed using SPSS version 17.
      Chi-square, Student's t-test, and logistic regression were used. A P <= 0.05 was
      considered statistically significant. RESULTS: In the study group, 73.3% of
      mothers had caries as compared to only 53.3% mothers in control group. While mean
      DMFT and mean DMFS of mothers in the study group was 3.78 +/- 3.91 and 8.37 +/-
      12.2, respectively, the same for the mothers in the control group was 2.66 +/-
      3.01 and 5.8 +/- 5.3. Sixty (66.7%) out of ninety mothers in the study group had
      a high MS count as compared to only 40 (44.4%) mothers in control group (P =
      0.003). CONCLUSION: The present study showed that high salivary MS count and
      decay in mothers could be important risk indicators for the development of caries
      in their children.

PMID- 28492189
TI  - Restoring the voids of voices by signs and gestures, in dentistry: A cross
      sectional study.
AB  - AIMS: To help dentists to communicate with the hearing impaired patients, reach
      an accurate diagnosis and explain the treatment plan by learning some signs and
      gestures used in the nonverbal communication (NVC) and by devising some new signs
      and gestures related to dentistry which shall be easy to learn and understand
      both by the hearing impaired patients and the dentists. SETTINGS AND DESIGN: The
      study was carried out on 100 hearing impaired students in the age group of 10-14
      years in two special schools for hearing impaired children located in two
      different states of India, where different spoken languages and different sign
      languages are used. One dentist (expert dentist) was trained in the NVC and the
      other dentist (non expert dentist) had no knowledge of this type of
      communication, communicated the same sets of statements related to dentistry, to
      the hearing impaired children. One1 translator was assigned to judge their
      interactions. Students were asked to tell the interpreter at the end of each
      signed interaction what they understood from the statement conveyed to them by
      both the dentists. STATISTICAL ANALYSIS USED: All data collected were subjected
      to statistical analysis using Chi-square test and odds ratio test. RESULTS: In
      the special school of 1st state, the nonexpert dentist conveyed only 36.3% of the
      information correctly to the students, whereas the expert dentist conveyed 83% of
      the information correctly. In the special school of 2nd state, the nonexpert
      dentist conveyed only 37.5% of the information correctly to the students, whereas
      the expert dentist conveyed 80.3% of the information correctly. CONCLUSIONS:
      Dentists should be made aware of the NVC and signs and gestures related to
      dentistry should be taught to the hearing impaired students as well as the dental
      students.

PMID- 28492190
TI  - Decreased sleep in children and their behavioral problems in dental operatory.
AB  - PURPOSE: This study was conducted to examine the contribution of inadequate sleep
      and its associated factors, on behavior and cooperation of children in the dental
      operatory. MATERIALS AND METHODS: A cross-sectional study was conducted on 100
      healthy children at the time of their initial visit to the dental hospital,
      ranging from preschoolers to adolescents. Data acquisition was done by a
      questionnaire. Interview with the accompanying person was done to ask about the
      sleep duration, naps, and sleep habits of the child. Children's behavior during
      their preliminary examination was studied and categorized according to Frankl's
      behavior rating scale. Data were analyzed by linear regression analysis and
      Spearman's correlation with the aid of SPSS 16.0 software. RESULTS: Total
      duration of sleep accounted for a small but significant contribution in
      behavioral problems of children. Significant correlation was found between
      duration of sleep and cooperative behavior in dental operatory (R = 0.478).
      However, the duration of sleep was negatively correlated to the number of
      siblings and socioeconomic status of the family. CONCLUSION: Children who had
      shorter total sleep duration had increased behavioral problems in dental
      operatory.

PMID- 28492191
TI  - Prevalence of dental fear and its causes using three measurement scales among
      children in New Delhi.
AB  - INTRODUCTION: There is a great need for identifying fearful children, who often
      present problems in patient management, thus affecting the quality of dental care
      rendered to them. This study is unique in the way that dental fear was assessed
      through three fear scales as research has suggested the use of more than one
      scale because each scale has its own restrictions and is open to criticism. AIM:
      The aim of this study was to evaluate dental fear and anxiety (DFA) among
      children aged 3-14 years using three fear measurement scales. METHODS: The study
      was conducted on children (3-14 years) who visited the Department of Pedodontics
      and Preventive Dentistry at Maulana Azad Institute of Dental Sciences, New Delhi.
      The DFA levels were measured using three fear measurement scales, i.e., facial
      image scale (FIS), dental fear scale (DFS), and children's fear survey schedule
      dental subscale (CFSS-DS). The dental behavior was estimated using the Frankl's
      behavior rating scale (FBRS). RESULTS: The prevalence of dental fear according to
      FIS was 14.3%, according to DFS was 22.6%, and according to CFSS-DS was 7.4%. In
      assessment of the behavior of children in the clinics through FBRS, it was
      observed that he maximum number of respondents (69.8%) showed Frankl's Rating 3
      i.e. positive. In the DFS and CFSS-DS, the factor which caused most fear was
      "feeling the needle injected" and "injections," respectively. CONCLUSION:
      Assessment of dental fear is an extremely useful tool for the dental
      practitioner, who can use it to customize the behavioral treatment and management
      for child patients.

PMID- 28492192
TI  - Association between family structure and oral health of children with mixed
      dentition in suburban Nigeria.
AB  - CONTEXT: Family structures can affect the oral health of the child. However,
      little is known about the impact of the family structure on oral health of
      children in Africa. AIMS: To determine the association between family structure,
      twice daily toothbrushing, use of fluoridated toothpaste, caries, and oral
      hygiene status of 5-12-year-old children resident in semi-urban Nigeria. SETTINGS
      AND DESIGN: Secondary analysis of the data of 601 children recruited through a
      household survey conducted in Ile-Ife, Nigeria. SUBJECTS AND METHODS: The
      association between dependent variables (presence of caries, good oral hygiene,
      use of fluoridated toothpaste, and twice daily toothbrushing) and the family
      structure (parental structure, number of siblings, and birth rank) was
      determined. STATISTICAL ANALYSIS USED: Simple and multivariate regression
      analysis was used to determine the association. The regression models were
      adjusted for age and gender. RESULTS: Children who were not primogenitor had
      significantly reduced odds of using fluoridated toothpaste (AOR: 0.91; 95%
      confidence interval [CI]: 0.85-0.97; P = 0.01) when compared with children who
      were primogenitors or only children. Furthermore, having 0-2 siblings
      significantly reduced the odds of having caries (AOR: 0.46; CI: 0.28-0.78; P <
      0.001) when compared with children who had three or more siblings. Children who
      used fluoridated toothpaste had significantly increased odds of having good oral
      hygiene (AOR: 1.64; 95% CI: 1.18-2.28; P < 0.001). CONCLUSIONS: For this study
      population, the number of siblings and the birth rank increased the chances of
      having caries and use of fluoridated toothpaste, respectively.

PMID- 28492193
TI  - Effectiveness of two different behavioral modification techniques among 5-7-year
      old children: A randomized controlled trial.
AB  - BACKGROUND: Dental fear is a common, essential, and inevitable emotion that
      appears as a response to the stressful situation, which raises children's anxiety
      level, resulting in reduced demand for pediatric dental care. AIMS: (1) To
      compare and evaluate the effectiveness of customized tell-play-do (TPD) technique
      with live modeling for behavior management of children. (2) To compare the
      behavioral modification techniques in managing the children during their dental
      visits. MATERIALS AND METHODS: Ninety-eight children aged 5-7 years were enrolled
      in the study and randomly allocated into two groups. Phase I: first visit. Group
      I - children were conditioned to receive various dental procedures using live
      modeling followed by oral prophylaxis. Group II - TPD technique was introduced
      with customized playing dental objects followed by oral prophylaxis. Phase II:
      second visit. After 7 days interval, all the study subjects were subjected to
      rotary restorative treatment. EVALUATION: Heart rate, Facial Image Scale (FIS),
      and Venham-6-point index were used before intervention, after intervention, and
      during dental procedure to quantify the anxious behavior. RESULTS: All 98
      children after intervention underwent oral prophylaxis on first visit and rotary
      restorative treatment on second visit. The average pulse rate, FIS, and Venham
      scale scores were significantly lower among children who received TPD
      intervention when compared to those who received live modeling intervention.
      Unpaired t-test at 5% level of significance was considered as statistical
      significance. CONCLUSIONS: TPD is effective in reducing children's fear and
      anxiety about dental treatment, children enjoy playing with customized dental
      object. Thus, to promote adaptive behavior, TPD could be an alternate behavioral
      modification technique during pediatric dentistry.

PMID- 28492194
TI  - Comparison of the Streptococcus mutans and Lactobacillus colony count changes in
      saliva following chlorhexidine (0.12%) mouth rinse, combination mouth rinse, and
      green tea extract (0.5%) mouth rinse in children.
AB  - BACKGROUND: Compounds present in green tea have been shown to inhibit the growth
      and activity of bacteria associated with oral infections. The purpose of this
      study was to compare the efficacy of chlorhexidine (0.12%) mouth rinse and
      combination (chlorhexidine and sodium fluoride) mouth rinse to that of green tea
      extract (0.5%) mouth rinse in reducing the salivary count of Streptococcus mutans
      and Lactobacillus in children. MATERIALS AND METHODS: The sample for the study
      consisted of 75 school children aged 8-12 years with four or more (decay
      component) of decayed, missing, and filled teeth index. Children were divided
      randomly into three equal groups and were asked to rinse with the prescribed
      mouth rinse once daily for 2 weeks after breakfast under supervision.
      Nonstimulated whole salivary sample (2 ml) was collected at baseline and
      postrinsing and tested for the colony forming units of S. mutans and
      Lactobacillus. RESULTS: The results of the study indicate that there was a
      statistically significant reduction in S. mutans and lactobacilli count in all
      the three study groups. The statistically significant reduction in the mean S.
      mutans and lactobacilli counts were more in 0.12% chlorhexidine group than in the
      combination mouth rinse and 0.5% green tea mouth rinse group. There was no
      statistically significant difference in the reduction of S. mutans and
      lactobacilli count between combination mouth rinse group and 0.5% green tea mouth
      rinse group. CONCLUSION: Green tea mouth rinse can be a promising preventive
      therapy worldwide for the prevention of dental caries.

PMID- 28492195
TI  - Evaluation of nitrous oxide-oxygen and triclofos sodium as conscious sedative
      agents.
AB  - BACKGROUND: Conscious sedation is used in the pediatric dentistry to reduce fear
      and anxiety in children and promote favorable treatment outcomes. To achieve
      them, the primary clinical need is for a well-tolerated, effective, and expedient
      analgesic and sedative agent that is safe to use. AIM: The aim of the present
      study was to evaluate the efficacy of nitrous oxide-oxygen and triclofos sodium
      as conscious sedative agents in 5-10-year-old children. METHODOLOGY: Sixty
      children aged 5-10 years showing anxious, uncooperative, and apprehensive
      behavior were randomly divided and assigned into two groups (Groups A and B) such
      that Group A received 40% nitrous oxide-60% oxygen and Group B received triclofos
      sodium in the dose of 70 mg/kg body weight, given 30 min before the treatment
      procedure. During the whole course of sedation procedure, the response of the
      child was assessed using Houpt's behavior rating scale. The acceptance of route
      of drug administration by the patient and parent was also assessed. Data obtained
      were statistically evaluated using the Mann-Whitney U-test and Chi-square test.
      RESULTS: Children sedated with triclofos sodium were significantly more drowsy
      and disoriented compared to those sedated with nitrous oxide. The overall
      behavior of children in both the groups was similar. Good parental acceptance was
      observed for both the routes of administration. Patients accepted the oral route
      significantly better than inhalation route. CONCLUSION: Both nitrous oxide-oxygen
      and triclofos sodium were observed to be effective sedative agents, for
      successful and safe use in 5-10-year-old dental patients. Patients showed a good
      acceptance of the oral route compared to the inhalation route for sedation.

PMID- 28492196
TI  - Comparative evaluation of effect of use of toothbrush with paste and munident on
      levels of Streptococcus mutans and gingival health in children: An in vivo study.
AB  - AIM: Dental caries is a multifactorial disease which has a deleterious effect on
      the oral cavity. Improper oral hygiene habits are a cause for the same. The aim
      of this study was to compare the antibacterial efficacy of Munident, an Ayurvedic
      (herbal) dentifrice with commercially available toothpaste. MATERIALS AND
      METHODS: A total of forty subjects between the age group 9 and 12 years, resident
      of Bala Yeshu Nilaya Bhavan, Mangalore, Karnataka, India, were chosen for our
      study. They were divided into two groups containing twenty subjects in each;
      Group 1 for standard toothpaste and Group 2 for Munident. The decayed, missing,
      and filled teeth scores were noted from each subject. Group 1 was instructed to
      brush the teeth using commercially available toothpaste and Group 2 was
      instructed to brush using commercially available Munident (herbal) dentifrice.
      Both the groups brushed the teeth using soft variety of tooth brush. The gingival
      bleeding index and salivary Streptococcus mutans count were noted pre- and post
      brushimg for both groups. The results obtained were subjected to statistical
      analysis. RESULTS: Munident (herbal) dentifrice showed better efficacy in
      comparison to toothpaste in terms of gingival bleeding index and salivary S.
      mutans count. CONCLUSION: Munident (herbal) dentifrice has better gingival
      bleeding index compared to standard formulation of toothpaste. Hence, the
      practice of using herbal dentifrice should be encouraged.

PMID- 28492197
TI  - The effect of atraumatic restorative treatment on adhesive restorations for
      dental caries in deciduous molars.
AB  - BACKGROUND: Minimal invasive approaches to managing caries, such as partial
      caries removal techniques and atraumatic restorative treatment (ART), are showing
      increasing evidence of improved outcomes over the conventional complete caries
      removal. OBJECTIVE: To evaluate clinically and radiographically the effect of ART
      on restorations using restorative cement and glass ionomer cement (GIC) for
      dental caries in the deciduous molars of children aged between 4 and 8 years.
      SETTINGS AND DESIGN: The study design was a split-mouth, randomized, blind
      clinical trial. MATERIALS AND METHODS: Eighty-six patients had 108 restorations
      placed with GIC (Ketac Molar Easy Mix - 3M ESPE) and 108 restorations placed with
      composite resin (CR) (Filtek Z250 - 3M ESPE). The restorations were assessed by
      means of images obtained with a digital camera and periapical radiographs at
      baseline and after 12 months of follow-up. STATISTICAL ANALYSIS: The Student's t
      test, Pearson Chi-squared test, and Bonferroni paired comparison test were used
      to evaluate the differences in proportions and correlations between the
      variables. RESULTS: After 12 months of follow-up, the restorations were
      considered clinically successful in 89.3% of cases and radiographically
      successful in 80.5% of cases. There was statistical difference neither between
      the two restorative materials used nor between the numbers of restored surfaces.
      CONCLUSIONS: GIC and CR can be used successfully for restorations of one or two
      dental surfaces after ART.

PMID- 28492199
TI  - An infant case of intraoral penetrating injury with a toothbrush causing
      retropharyngeal and upper mediastinal emphysema.
AB  - A 2-year-old male child who was running and fell with a toothbrush in his mouth
      suffered an injury to the inside of his right cheeks. His mother noticed that the
      toothbrush had impaled his mouth, and removed it. On arrival, a wound was
      observed on the right cheeks and palate. His general condition was good. However,
      computed tomography revealed emphysema from the left side of epipharynx to the
      upper mediastinum. This patient shows the importance of not only checking the
      medical history and performing a physical examination but also performing an
      imaging examination.

PMID- 28492198
TI  - Comparison of efficacy of three chemotherapeutic agents on Streptococcus mutans
      count in plaque and saliva: A randomized controlled triple blind study.
AB  - BACKGROUND: There is a need for exploration of the role of chemotherapeutic
      agents and its role in the prevention of early childhood caries (ECC) and its
      recurrence. AIM: The aim of this study was two-fold: (1) To compare the
      antimicrobial efficacy of three commonly used chemotherapeutic agents in the
      prevention of ECC in comparison with a control and (2) To ascertain the role of
      chemotherapeutic agents in the prevention of ECC. MATERIALS AND METHODS: Sixty
      children with ECC in the age group 3-6 years were randomly allocated into four
      groups. To each group of children after full oral rehabilitation either 10%
      povidone-iodine (PI), or chlorhexidine (CHX) varnish (Cervitec Plus), or fluoride
      varnish (Fluor Protector) were applied twice at an interval of 1 week, Group 4
      served as control. Streptococcus mutans count in saliva and plaque were collected
      at baseline, 30, 60, and 90 days and the presence of S. mutans was evaluated
      using the Dentocult SM strip mutans kit. The efficacy of 10% PI, CHX varnish
      (Cervitec Plus), and fluoride varnish (Fluor Protector) was compared with the
      control group at 30, 60, and 90 days. An intergroup comparison was also done
      during the same time intervals. RESULTS: The reduction of S. mutans count in the
      plaque and saliva was greatest in the fluoride varnish treated groups at all time
      intervals (30, 60, and 90 days). Fluoride varnish, CHX varnish, and 10% PI showed
      significant improved efficacy when compared to the control group (P < 0.001).
      Fluoride varnish showed significantly lower counts of S. mutans compared to CHX
      varnish at all time intervals (30, 60, and 90 days) and also significantly lower
      counts compared to 10% PI at 60 and 90 days interval (P < 0.001).

PMID- 28492200
TI  - Anesthesia-related mortality in pediatric patients in dental office setting.

PMID- 28492201
TI  - Erratum: Determination of toral antioxidant capacity of saliva in sickle cell
      anemic patients - A cross-sectional study.
AB  - [This corrects the article DOI: 10.4103/0970-4388.199219].

PMID- 28492202
TI  - Spirometric evaluation of ventilatory function in adult male cigarette smokers in
      Sokoto metropolis.
AB  - BACKGROUND: Cigarette smoking is a widespread social habit in Nigeria with
      extensive deleterious multisystemic effect. Ventilatory dysfunction is one of the
      cigarette smoking-related illnesses that affect the respiratory system.
      Spirometry is an investigative method that can be used for the early detection of
      ventilatory dysfunction even before the onset of the symptoms. SUBJECTS AND
      METHODS: A questionnaire adapted from the European Community Respiratory Health
      Survey was administered to collect demographic, clinical, and cigarette smoking
      data. Ventilatory function test was conducted using Clement Clarke (One Flow)
      Spirometer, version 1.3. The highest value of each ventilatory function index was
      chosen for analysis, and individual(s) with ventilatory dysfunction were
      subjected to post bronchodilator spirometry. RESULTS: For the purpose of this
      research, 150 participants who were currently cigarette smokers were enrolled,
      and 50 apparently healthy, age-matched individuals who were never smokers served
      as controls in the ratio of 3:1. Eighty percent of participants and 68% of
      controls were aged 40 years or below. The mean age of participants (34.27 +/-
      8.91 years) and the controls (35.08 +/- 10.35 years) was not significantly
      different (P = 0.592). Similarly, there were no statistically significant
      differences between the mean anthropometric indices (weight: P = 0.663, height: P
      = 0.084, and body mass index: P = 0.099) of both participants and controls. The
      mean values of FEV1 (forced expiratory flow in one second) and FEV1/FVC
      (FVC=forced vital capacity) were lower in the participants compared to the
      controls, and this difference was statistically significant (P < 0.001). There
      was a weak negative correlation between pack-years of cigarette smoking and FEV1
      (r = -0.237 and P = 0.004). Obstructive ventilatory defect was found among six
      study participants (4%) and two controls (4%). CONCLUSION: Cigarette smoking is
      associated with decline in ventilatory function test indices (FEV1 and FEV1/FVC)
      in adult males. Decline in FEV1 is directly related to pack-years of cigarette
      smoking.

PMID- 28492203
TI  - Assessment of tobacco control efforts in three Sub-Saharan African countries.
AB  - BACKGROUND: Tobacco industry's undermining of tobacco control goes on unabated in
      sub-Saharan African countries, especially in Kenya, Nigeria, and Uganda. The
      Framework Convention on Tobacco Control (FCTC) contains provisions aimed at
      curbing these activities. However, the level to which FCTC is implemented and the
      strength of each country's tobacco control law will determine its usefulness in
      this regard. We determined the implementation status and strength of tobacco
      control laws in Kenya, Nigeria, and Uganda. MATERIALS AND METHODS: The World
      Health Organization and Campaign for Tobacco-Free Kids websites were queried for
      secondary data related to tobacco control. Sources and data were disambiguated
      and reported as tables. Composite scores for implementation were computed based
      on the number of indicators of the articles of the FCTC reported on by each
      country. Strength of tobacco control law (SoTCL) was computed based on the total
      number of domains of the laws meeting a defined acceptable standard. Total
      obtainable score for implementation and SoTCL were 148 and 38, respectively.
      RESULTS: On the FCTC, Kenya, Nigeria, and Uganda achieved 75, 61.5, and 46.6%
      implementation, respectively. SoTCL was weakest in the smoke-free domain for
      Kenya, tobacco advertisement promotion and sponsorship domain for Nigeria, and
      packaging and labeling domain for Uganda. SoTCL scores were 18 (47.4%), 20
      (52.6%), and 34 (89.5%) for Nigeria, Kenya, and Uganda, respectively. CONCLUSION:
      Kenya, Nigeria, and Uganda will need to strengthen their tobacco control laws
      through appropriate amendment as well as regulatory mechanisms that guarantee
      alignment with FCTC and the implementation thereof.

PMID- 28492204
TI  - Impact assessment study after 27 years of community-directed treatment with
      ivermectin in Galadimawa, Kaduna State, Nigeria.
AB  - PURPOSE: To assess the impact on blindness after 27 years of community-directed
      treatment with ivermectin (CDTI) in the Galadimawa community of Kauru Local
      Government in Kaduna state, Nigeria. The population of Galadimawa constituted
      about 12% of the total population examined during the ivermectin randomised
      control trial (RCT) in 1989. The RCT population of 8000 individuals was scattered
      over 36 villages in Kaduna state. Thus, longitudinal data are available on
      blindness. MATERIALS AND METHODS: After 27 years of dosing with ivermectin, the
      people in the community of Galadimawa were re-examined for the prevalence and
      causes of blindness. This was achieved by an examination of the visually
      disabled. The findings were compared with the situation in 1989 before the dosing
      commenced. RESULTS: The population of the village increased from 711 to 1419. The
      prevalence of blindness dropped from 4.9 to 0.96%. The most common causes of
      blindness were now cataract (55.2%) and optic atrophy (27.6%), whereas the most
      common causes in 1989 were onchocerciasis (28.3%), glaucoma (17.4%) and cataract
      (10.9%). People with optic atrophy were more likely to have taken fewer doses of
      ivermectin over the years. The blind people encountered in 2016 were on average
      17 years older than those seen in 1989, which suggests that blindness, when it
      occurs, is delayed by almost two decades. CONCLUSION: CDTI has reduced the
      prevalence of blindness significantly in Galadimawa and may reflect the situation
      elsewhere in the Kaduna state, which is an oncho-endemic zone.

PMID- 28492205
TI  - The identification and grading of the psychosocial impact of Tinea capitis in
      primary school children in a semi-urban area of Rivers State, Nigeria.
AB  - INTRODUCTION: Tinea capitis is a fungal skin disease, which is not life
      threatening but could affect the psychosocial life of those suffering from it.
      Thus, this study sought to identify and grade the psychosocial impact related to
      Tinea capitis in primary school children. SUBJECTS AND METHODS: This was a cross
      sectional study involving primary school children in Emohua Local Government Area
      of Rivers State. These children had been clinically diagnosed with Tinea capitis.
      The Children Dermatology Life Quality Index instrument was used to identify the
      presence of a psychosocial impact, which was graded as none, mild, moderate, and
      severe. The Statistical Package for Social Sciences version 20 software was used
      for analysis, and statistical significance was set at P < 0.05. RESULTS: A total
      of 184 children aged 6-12 years with Tinea capitis participated in the study. The
      mean age of the children was 9.5 +/- 2.9 years. The male-to-female ratio was
      2.5:1. More than half of the children (58.2%, n = 127) had mild-to-severe
      psychosocial impact. The psychosocial impact was significantly higher (P = 0.02)
      among the female children (61.5%; n = 32) than the male children (41.7%; n = 20).
      In addition, female children with Tinea capitis were 2.2 times more likely to
      suffer a psychosocial impact than their male counterparts (odds ratio = 2.2; 95%
      confidence interval: 1.16-4.32). There were no significant differences in the
      psychosocial impact across the age categories (P = 0.859). CONCLUSION: Tinea
      capitis has a psychosocial impact on the daily lives of school children, with
      more than half of the children experiencing mild-to-severe grades of psychosocial
      impact. Collaboration between mental health physicians and pediatric
      dermatologists is encouraged to address the effect of Tinea capitis on the
      psychosocial life of school children, especially the female children.

PMID- 28492206
TI  - Community screening for pre-hypertension, traditional risk factors and markers of
      chronic kidney disease in Ondo State, South-Western Nigeria.
AB  - BACKGROUND: Chronic kidney disease (CKD) has become an epidemic with many
      recognised risk factors. However, the role of pre-hypertension in CKD is yet to
      be fully studied in our environment. OBJECTIVES: We set out to determine the
      magnitude of pre-hypertension and traditional CKD risk factors. We also
      determined their relationships to proteinuria. SUBJECTS AND METHODS: This was a
      descriptive, cross-sectional study conducted in two urban local government areas
      (Akure South and Ondo West) in Ondo State, Southwest Nigeria in March 2014. A
      total of 1,183 adults (M:F, 0.63:1) were studied. Their bio-data, history of
      cigarette smoking, alcohol intake, herbal usage, non-steroidal anti-inflammatory
      drugs (NSAIDs), diabetes and hypertension were obtained. A total of 1,183 adults
      (M:F, 0.63:1) blood pressure (BP) and anthropometry were determined. Urinalysis
      was conducted using Combi-Uriscreen(r) 10SL. Data were analysed using the
      Statistical Package for the Social Sciences version 20.0. RESULTS: A total of
      1183 adults (M:F, 1:1.6) were studied with a mean age of 44.7 +/- 17.4 years.
      Their mean systolic BP, diastolic BP and body mass index were 129.6 +/- 23.7
      mmHg, 79.8 +/- 14 mmHg and 26.2 +/- 5.8 kg/m2, respectively. Pre-hypertension was
      present in 32.3% of the subjects, while hypertension was present in 43.4% of the
      subjects; 6.2% gave history of diabetes, 4.5% smoked cigarette, 68.3% used herbs
      and 44.1% used NSAIDs. Proteinuria was present in 25.9% of the subjects, while
      haematuria was present in 1.7% of the subjects. BP and age showed significant
      association to proteinuria. CONCLUSION: Pre-hypertension and known risk factors
      of CKD are prevalent in the people of Ondo State, Nigeria. Individuals with
      persistent pre-hypertension should be routinely screened for CKD and referred to
      the Nephrologist for early intervention.

PMID- 28492207
TI  - Research experience of resident doctors who attended research methodology courses
      of the National Postgraduate Medical College of Nigeria.
AB  - INTRODUCTION: For over three decades, the National Postgraduate Medical College
      of Nigeria (NPMCN) has been vested with the responsibility of overseeing
      postgraduate medical training. The main objective of this study was to assess the
      residents' perception of research as well as challenges faced in pursing seamless
      research during their training. MATERIALS AND METHODS: This study was a cross
      sectional descriptive survey in 2013. Self-administered questionnaires were
      distributed to the participants of the annual research methodology workshop in
      all the 15 faculties of the NPMCN. The questionnaires assessed the residents'
      previous exposure to research, their publication history and their trainers'
      input to their own research. Statistical analysis was performed using the
      Statistical Package for the Social Sciences version 20 software. RESULTS: Four
      hundred and one resident doctors, out of a total of 415 who attended the course,
      completed the questionnaires during the study period (96.6% response rate). There
      were 269 (67.0%) males and 132 (33.0%) females, giving a male-to-female ratio of
      2:1. About three-quarters of them admitted that their exposure to research during
      training was grossly inadequate. Twenty-five percent of them were involved in a
      previous research before residency training, and a further 70% of respondents
      were involved in their trainers' research work. Ninety-four percent in our study
      identified a lack of dedicated time to be spared for research as a major obstacle
      to research. CONCLUSION: Contribution and exposure to research among postgraduate
      trainees in Nigeria are low. Lack of dedicated time for research was viewed as
      the major obstacle to research by most residents.

PMID- 28492208
TI  - Self-reported dental pain and dental caries among 8-12-year-old school children:
      An exploratory survey in Lagos, Nigeria.
AB  - BACKGROUND: Dental pain is considered an important public health problem because
      it affects the daily life of children. This study was designed to assess the
      prevalence, associated factors, and impact of dental pain among 8-12-year-old
      school children in Lagos, Nigeria. SUBJECTS AND METHODS: A cross-sectional survey
      to determine self-reported dental pain among 8-12-year-old school children using
      an interviewer-administered questionnaire was conducted. This was followed by a
      clinical examination to determine the child's oral hygiene status and dental
      caries status. Chi-square and Fisher's exact tests were used for comparing
      proportions. Binary logistic regression analysis was also conducted. Statistical
      significance was set at P < 0.05. RESULTS: Of the 414 children included in the
      survey, 254 (61.4%) children and 103 (24.9%) children reported experiencing
      dental pain 3 months and 4 weeks before the survey, respectively. Caries
      prevalence was 21.0%, whereas mean decayed, missing, and filled tooth index score
      was 0.4420 (+/-1.078). A report of pain up to 3 months before the survey was
      significantly associated with the child's age [odds ratio (OR) = 1.254;
      confidence interval (CI) = 1.037-1.516; P = 0.019], whereas the type of school
      attended (OR = 1.786; CI = 1.124-2.840; P = 0.014) and the presence of dental
      caries (OR = 1.738; CI = 1.023-2.953; P = 0.041) were significantly associated
      with reporting pain 4 weeks before the survey. CONCLUSION: The prevalence of self
      reported dental pain was high among the children surveyed. Report of dental pain
      was associated with the presence of dental caries. The provision of school oral
      health services could be useful in reducing the level of untreated caries and
      possibly dental pain among school children.

PMID- 28492209
TI  - Some characteristics of gliomas managed at a Neurosurgery centre in Nigeria.
AB  - BACKGROUND: Gliomas are important primary brain tumours with varying prognosis.
      AIM: To study the histology characteristics of brain gliomas managed in a
      Neurosurgical centre in Nigeria. MATERIALS AND METHODS: A retrospective analysis
      of prospectively recorded data of patients managed for intracranial gliomas at
      our Hospital for Neurosurgery, between year 2006 and 2015. Only the patients with
      conclusive histology diagnosis following surgery were analysed. RESULTS: Glioma
      was 23.8% of the 252 histology-confirmed brain tumours. Male-to-female ratio was
      1.4:1.0. Peak age at diagnosis was in the fifth decade of life. There was an
      increase in the frequency of diagnosis from seven (2006-2009) to 15 (2011 and
      2012) and 39 patients managed (2013 and 2015). In sub-group analysis, grade IV
      tumour was the most common (34.6%) followed by grade II (30.7%), grade I (18.3%)
      and grade III (16.7%). Seven patients of grade II oligodendroglioma and one
      patient each of anaplastic oligodendroglioma, subependymal giant cell astrocytoma
      and astroblastoma were seen. The anatomical location of the tumour was the
      frontal lobe in 23.3% of patients followed by the parietal lobe in 16.7% of
      patients. The pre-operative Karnofsky score was >=70% in 36.7% of the patients.
      CONCLUSION: Gliomas are more common brain tumours than were imagined. Most
      patients present relatively late and with advanced disease. High-grade gliomas
      seem to mostly affect the middle age population in the study environment with
      higher proportion of grade IV lesions.

PMID- 28492210
TI  - Predictors of quality of life in patients with diabetes mellitus in two tertiary
      health institutions in Ghana and Nigeria.
AB  - BACKGROUND: Patients with chronic diseases such as Type 2 diabetes mellitus (DM)
      usually have a relatively poor quality of life (QoL), because the cost of care
      (living expenses and health) or diet restrictions are heavily felt by these
      patients, and this is of a public health concern. However, limited data on DM QoL
      exist in Ghana and Nigeria. This makes it imperative for data to be collated in
      that regard. MATERIALS AND METHODS: We adopted the Strengthening The reporting of
      observational studies in epidemiology (STROBE) consensus checklist to survey the
      patients with DM seen at the diabetic clinic at the Department of Medicine of the
      Korle-Bu Teaching Hospital and University College Hospital, Ibadan, Nigeria.
      Patients with Type 2 DM aged 40 years and older were recruited by using
      systematic random sampling method. The World Health Organization Quality of Life
      BREF, diabetes empowerment scale, and DM knowledge scale were used to assess QoL,
      patient empowerment, and knowledge of DM, respectively. The predictors of QoL
      were determined using multiple linear regression analyses. RESULTS: A total of
      198 patients in Ghana and 203 patients in Nigeria completed the survey, with
      female-to-male ratio being 3:1 and 2:1, respectively. The overall QoL in both
      countries was relatively low: 56.19 +/- 8.23 in Ghana and 64.34 +/- 7.34 in
      Nigeria. In Ghana, significant correlates of higher scores on the QoL scale were
      medication adherence (P = 0.02) and employment status (P = 0.02). Among patients
      in Nigeria, employment status (P = 0.02) and DM empowerment (0.03) were
      significant predictors of QoL in patients with DM. CONCLUSION: Our study revealed
      an association between a number of psychosocial factors and QoL among patients
      with DM in Ghana and Nigeria.

PMID- 28492212
TI  - Isolated sternal cleft in a patient with atrial septal defect: A rare sole
      association.
AB  - Sternal cleft (SC) is a rare form of chest wall deformity with an incidence of
      <0.15%. It occurs because of failure of fusion of the sternal bars about the 7
      9th week of intrauterine life. It could occur in isolation or as a part of a
      syndromic complex. This condition exposes the vital mediastinal structures to a
      huge risk of injury, aside from cosmetic issues. Treatment in the neonatal period
      is most favourable, though other modalities are available in the later stages of
      life, but it can be challenging. We present the case of a 2-month-old female
      infant with a superior SC with a single association of secundum atrial septal
      defect. She was asymptomatic. She was treated by primary repair to protect the
      underlying mediastinal structures as well as for cosmetic reasons. Such a repair
      resulted in good clinical outcome.

PMID- 28492211
TI  - Raised adenosine deaminase in the cerebrospinal fluid: A tool for the diagnosis
      of tuberculous meningitis in developing countries.
AB  - CONTEXT: The rapid diagnosis followed by the early treatment of tuberculous
      meningitis (TBM) is important in preventing fatal outcomes. The mainstay of
      diagnosis lies in cerebrospinal fluid (CSF) analysis, radiological
      investigations, and clinical findings. AIM: The present study was conducted to
      determine the efficacy, sensitivity, and specificity of raised adenosine
      deaminase (ADA) level in CSF to differentiate TBM from non-TBM cases as a rapid,
      cost-effective, and noninvasive test. PATIENTS AND METHODS: This was a
      retrospective study conducted over a 1-year period in a tertiary teaching
      institute of Malwa region, India. A total of 143 patients presented with symptoms
      and signs of meningitis were included and divided into TBM and non-TBM groups on
      the basis of the diagnostic criteria. CSF ADA estimation was drafted and analyzed
      by using >=10 U/L as a cutoff value. A statistical comparison of the ADA levels
      between the study groups was made by using unpaired Student's t-test. RESULTS:
      Out of the 143 cases, 40 were TBM, and 103 were non-TBM. The mean ADA level in
      TBM and non-TBM cases was 17.18 +/- 9.59 and 6.33 +/- 2.48, respectively, and the
      difference was statistically significant. Using a cutoff level >=10 U/L, CSF ADA
      had a sensitivity of 92.5% and a specificity of 89.32%. Positive and negative
      likelihood ratios of the test were 8.66 and 0.08, respectively, and positive and
      negative predictive values, were 77.08 and 96.84%, respectively. CONCLUSION: The
      present study reflects the importance of a CSF ADA level >=10 U/L in the
      diagnosis of TBM. Thus, it can be used as an adjunctive diagnostic tool to
      differentiate TBM from other non-TBM cases, when there is a diagnostic dilemma.

PMID- 28492213
TI  - Psychiatry outside the framework of empiricism.
AB  - Science is interested in whatever that is empirical and objective. Any claim that
      cannot be objectively demonstrated has no place in science, because the subject
      does not deviate from the role, which it has set out to play in the life of
      mankind. Psychiatry, as a scientific discipline, plays along these basic
      principles. In the etiology, symptomatology, and management of psychiatric
      disorders, the biopsychosocial model recognizes the role of biological,
      psychological, and social factors. This essay views psychiatry from the
      biopsychosocial perspective and asserts that certain elements, which may not be
      readily and empirically verifiable, are important in the practice of psychiatry.

PMID- 28492214
TI  - The Faculty of Health Studies at the University of Mostar in the Service of
      Health.
AB  - The continuous progress of science has a very positive effect on health care.
      Health care in its broader sense has greatly progressed in past decades, and the
      education of health care professions requires more continuous learning, teaching
      materials and course duration. It becomes clear that continuous education is not
      only important for good quality doctors, but all participants of health care are
      gaining more burdens and their work becomes more complex. There is an increased
      necessity for team work, division of tasks and specialization. In this battle for
      health, the Faculty of Health Studies becomes a necessity and has an obligation
      in education of various health personnel due to acquiring practical and
      theoretical skills, as well as abilities in providing the best possible health
      care. The path of knowledge is long and difficult. It has been present at our
      faculty for 17 years and we carry it out through a variety of undergraduate and
      graduate programs, and as of this years through our postgraduate program. Besides
      the education of health care workers we wanted to offer to our current and former
      students, and their educators the possibility of publishing their work, so in
      2015 we launched our electronic journal, "Health Bulletin", whose publisher is
      the Faculty of Health Studies. In the process of continuous battle for health,
      prevention and treatment, the role of highly educated health care worker is of
      increasing importance and he certainly becomes an indispensable link in this
      process. The goal of our faculty is to educate the best possible health care
      workers, who will in addition to high quality practical work gradually take over
      our teaching responsibilities at the university.

PMID- 28492215
TI  - Public Health Achievements and Challenges: Symposium of the University of Mostar
      Faculty of Health Studies.
AB  - Public health is an important area of health care that reflects the readiness of
      the state and society to provide the welfare of all citizens through the
      promotion of health and the preservation of a healthy environment - factors that
      directly affect the health of the population. The field of public health is very
      broad and its concept is changing over time, being defined in a narrower and
      wider sense. In short, public health is a science and practice that aims at
      ensuring the conditions in which people can preserve and improve their health and
      prevent health damage. The third millennium brings its specifics, needs and
      priorities according to challenges public health is faced by in the twenty-first
      century: the economic crisis, rising inequality, population aging, rising rates
      of chronic diseases, migration, urbanization, ecosystem change, climate change,
      etc. The role of public health is to protect, improve health, prevent diseases
      and injuries. Such a public health approach implies a multisectoral work focusing
      on "wider health determinants", and within this activity experts from various
      medical and non-medical profiles, whose field of public health is concerned, can
      be found. The development of inter-departmental co-operation skills contributes
      to a better understanding of health professionals and professionals of other
      profiles, and facilitates common, synergistic actions in addressing public health
      problems in the community. Symposium on Public Health Achievements and Challenges
      organized by the University of Mostar Faculty of Health Studies is just another
      indication of the obligation, the need and the desire for professional and
      scientific contribution to the fight for better health. Our faculty has so far
      organized other numerous symposia, and the aim of this symposium is to present
      public health achievements and challenges in our surrounding in order to protect,
      improve health, prevent diseases and injuries in a modern way.

PMID- 28492216
TI  - Psychological Status and Quality of Life in Acne Patients Treated with Oral
      Isotretinoin.
AB  - INTRODUCTION: The acne patients are at higher risk of acquiring depresion and
      anxiety, which can lead to reduced quality of life. Effective treatment of acne
      can reduce symptoms of anxiety and depression and significantly improve other
      physiological parameters and quality of life of these patients. The aim of this
      study was to determine the psychological status and quality of life of acne
      patients before, during and after the treatment with oral isotretinoin. SUBJECTS
      AND METHODS: The prospective study included a total of 127 patients suffering
      from moderate to severe form of acne. To assess the psychological status and
      quality of life of studied groups the following standard psychometric
      questionnaires were performed before, during and after the treatment with oral
      isotretinoin: Beck Depression Inventory (BDI), Assessments of the Psychological
      and Social Effects of Acne (APSEA), State Trait Anxiety Inventory (STAI), Measure
      of Psychological Stress (MPS) and Dermatology Specific Quality of Life (DSQL).
      RESULTS: Results of the present study indicate that there is no increase in
      depressive and anxiety symptoms in the patients treated with oral isotretinoin.
      The psychological status by gender has shown the existence of differences between
      the genders in all measures of psychological status. Statistically significantly
      better quality of life was observed after healing than before treatment.
      CONCLUSION: The results of our study showed no higher risk of depression and
      anxiety within the patients with acne treated with oral isotretinoin. Improvement
      of quality of life after the treatment of acne with oral isotretinoin was
      confirmed.

PMID- 28492217
TI  - Prevalence of Intellectual Disabilities and Epilepsy in Different Forms of
      Spastic Cerebral Palsy in Adults.
AB  - BACKGROUND: Spastic cerebral palsy may be interconnected with other
      neurodevelopmental disorders such as intellectual disabilities, and epilepsy.
      Brain synaptic plasticity and successful restorative rehabilitation may also
      contribute to diminish neurological deficit of patients having cerebral palsy.
      The aim of this study was to investigate the prevalence of intellectual
      disabilities and epilepsy in adult patients with different forms of spastic
      cerebral palsy and to find out correlation between the severity level of
      intellectual disabilities and epilepsy. SUBJECTS AND METHODS: Adults diagnosed
      with different forms of spastic cerebral palsy were analyzed during a three-month
      period. The investigated features were: gender and age; form of cerebral palsy;
      the prevalence of intellectual disabilities and epilepsy. Intellectual
      disabilities were divided into 4 severity levels. The correlation between the
      severity level of intellectual disabilities and epilepsy was statistically
      analyzed. RESULTS: Intellectual disability was present in 55% of patients
      diagnosed with spastic cerebral palsy. Epilepsy was present in 36% of such
      patients. It was recorded in 51.1% of quadriplegic, 21.9% of diplegic, and 19.2%
      of hemiplegic patients. Intellectual disability was present in 73.8% of
      quadriplegic, 31.3% of diplegic, and 53.8% of hemiplegic patients. The
      statistically significant correlation existed between the severe intellectual
      disability and epilepsy. CONCLUSIONS: Intellectual disabilities and epilepsy most
      frequently occurred in patients with most severe forms of spastic cerebral palsy.
      Epilepsy is strongly correlated to the severity level of intellectual disability.
      Such patients require additional special modes of treatment and restorative
      rehabilitation to improve the functional outcome.

PMID- 28492218
TI  - The Impact of Religiosity on Quality of Life and Psychological Symptoms in
      Chronic Mental Patients.
AB  - INTRODUCTION: In recent decades, there is more and more scientific research and
      evidence that religiosity has a positive impact on quality of life and mental
      health. The aim this study is to evaluate the impact of religiosity on the
      quality of life and psychological symptoms of chronic mental patients. SUBJECTS
      AND METHODS: The test group was consisted of 100 chronic mental patients at the
      Clinic for Psychiatry UCH Mostar, and control group was consisted of 80 somatic
      patients surveyed from the Infirmary of family medicine of the Health Center
      Mostar. The survey was conducted by the social and demographic questionnaire, a
      questionnaire on the quality of life of the World Health Organization WHOQOL
      BREF, the questionnaire on religiosity and self-assessment questionnaire for
      psychological symptoms SCL-90th. RESULTS: For the socio-demographic data we
      obtained results that chronic mental patients as opposed to chronic somatic
      patients have significantly higher percent of an average lifestyle habits. There
      is statistically significant difference in the place of residence, chronic mental
      patients live in the city as opposed to somatic who live in the countryside. On
      the question of religiosity we received information that the chronic mental
      patients in relation to chronic somatic patients significantly more attend public
      religious gatherings, but however, chronic somatic patients compared to chronic
      mental significantly more use religiosity for better financial position, social
      comfort. In self evaluation of psychological symptoms we received information
      that the chronic mental patients as opposed to chronic somatic patients had
      significantly more psychotic features. To test the quality of life between the
      two groups, we received the information that chronic mental patients have
      significantly better physical and mental health, social relationships and caring
      for the environment as opposed to chronic somatic patients. CONCLUSIONS: Quality
      of life was significantly better in the chronic mental patients. Also, chronic
      mental patients significantly more attend public religious gatherings, while
      chronic somatic patients significantly more use religiosity for a better
      financial position, social comfort. Finally, chronic mental patients had a
      significantly more pronounced psychotic features.

PMID- 28492219
TI  - Kappa Free Light Chains in Cerebrospinal Fluid of Patients with Identified
      Oligoclonal Immunoglobulin G.
AB  - BACKGROUND: Production of kappa free light chains (KFLC) represents a part of
      humoral immune response, along with the synthesis of intrathecal immunoglobulins.
      Increased concentrations of immunoglobulin G light chains, kappa and lambda
      chains, were identified through research of numerous diseases of central nervous
      system. The qualitative method of isoelectric focusing (IEF) followed by
      immunofixation currently represents the accepted standard in identifying
      oligoclonal bands (OCB), but establishing a sensitive immunonephelometric method
      for quantification of kappa free light chains (KFLC) in cerebrospinal fluid (CSF)
      has paved a way for new diagnostic possibilities. Andersson classified the
      pattern types of OCB, ranging from type 1 to type 5, wherein types 2 and 3
      indicate intrathecal synthesis. Our aim was to determine KFLC in CSF of patients
      with clinically isolated syndrome (CIS) who had presented with type 2 and type 3
      OCB, to determine if there is a difference in concentrations between those two
      groups and to establish a borderline value of KFLC which would enable
      differential diagnostics. SUBJECTS AND METHODS: 70 patients, who underwent lumbar
      punction for CSF analysis and had their blood sampled through the cubital vein,
      participated in the study. Patients were classified according to Andersson as
      type 2 or type 3, which besides adulthood, represented the inclusion criteria.
      The average age of patients classified as type 2 was 36 years, and those
      classified as type 3 was 39 years, where it is evident that there was not a
      statistically significant difference (p=0.0685). We used a qualitative
      electrophoretic technique of IEF with agarose gel followed by immunofixation, and
      a quantitative immunonephelometric method. All results were interpreted on a
      level of statistic significance of p<0.05. RESULTS: CSF KFLC concentrations in
      type 3 were statistically and significantly elevated with regard to type 2 (Mann
      Whitney test, p=0.0430). The median for KFLC in type 2 was 0.9 mg/L, while the
      median for KFLC in type 3 was 2.71 mg/L, and the detection limit for both types
      was 0.18 mg/L. We used a statistical ROC curve to determine that KFLC
      concentration can be used for differential diagnostics, meaning it can
      discriminate type 2 from type 3 with clinical sensitivity of 61% and clinical
      specificity of 71% (AUC=0.641) (p=0.037). CONCLUSION: Despite the obtained
      statistically significant differences in concentrations of KFLC between types of
      OCBs and ROC analysis results, determination of KFLC by a nephelometric method,
      insufficiently strong clinical sensitivity and specificity does not justify
      abandonment of IEF method followed by immunofixation.

PMID- 28492220
TI  - Family Atmosphere and Relationships as Predictors of Heroin Addiction.
AB  - INTRODUCTION: Studies show that dysfunctional family relationships are important
      predictors of addictions to all psychoactive substances. OBJECTIVE: To establish
      if there is a connection between family relations and heroin addiction and if
      found to exist, what is the quality of this connection. SUBJECTS AND METHODS:
      This research was conducted on the sample comprised of 160 subjects divided into
      two groups. The first group consisted of 61 heroin addicts treated at the Tuzla
      University Clinical Centre Psychiatric Hospital. The second group consisted of 99
      subjects who were students at the Tuzla University Faculties of Philosophy and
      Electrical Engineering and who were not using any psychoactive substances. The
      subjects were tested with the Quality of Family Interactions Scale (KOBI) which
      measures the interactions between children and parents in two dimensions,
      described in literature as 'acceptance' and 'rejection'. RESULTS: The research
      team established statistically significant differences between the heroin addicts
      and the students, the non-users, in terms of their family relationships. The
      results show that the addicts families were characterized by lack of
      understanding, by conflicts, rejection, non-acceptance by parents, while the non
      users families were characterized by understanding, acceptance by parents and
      good communication. CONCLUSIONS: There is a connection between inter-family
      relationships and addiction. Namely, rejection and non-acceptance of
      children/persons by their families and parents, bad communication and
      dysfunctional family relationships are significant predictors of heroin
      addiction.

PMID- 28492221
TI  - Accuracy of Modified Alvarado Score, Eskelinen Score and Ohmann Score in
      Diagnosing Acute Appendicitis.
AB  - INTRODUCTION: By processing the data of a large number of patients with abdominal
      pain, diagnostic scores whose implementation attempts to facilitate acute
      appendicitis diagnostics were developed. Modified Alvarado score, Ohmann score
      and Eskelinen score are used as assistance when setting the diagnosis and making
      a decision to undertake surgery. AIM: To assess accuracy of Alvarado score,
      Ohmann score and Eskelinen score in diagnosing acute appendicitis and to
      establish connection of total score of these scoring systems with
      histopathological degree of appendicitis. SUBJECTS AND METHODS: A cross-sectional
      study was conducted at the Department of Surgery of University Clinical Hospital
      Mostar. The study included 70 patients who underwent appendectomy and were scored
      before surgery. All tested persons were examined by experienced surgeon who took
      anamnesis, physical status and ordered laboratory diagnostic tests. Appendicitis
      was excluded or confirmed by means of histopathological diagnostics, and the
      degree of appendicitis was determined. RESULTS: According to accuracy parameters
      (sensitivity, specificity, negative and positive predictive value), the score
      which was of highest value was Ohmann score, followed by Eskelinen score, while
      the lowest value was the one of modified Alvarado score. Total score in all three
      scoring systems follows the degree of appendicitis, but statistical significance
      was proven only for Ohmann and Eskelinen scores. CONCLUSION: Ohmann and Eskelinen
      scores can be useful in diagnosing acute appendicitis, predicting the degree of
      appendicitis, as well as assistance when making decision to undertake an
      operative procedure. Modified Alvarado score in our subjects did not prove
      sufficient value. Diagnostics of acute appendicitis still must be led by
      contemporary algorithms in which diagnostic scoring is implemented.

PMID- 28492222
TI  - A case report of a long time unrecognized hypochondriac patient wondering through
      the hospital departments.

PMID- 28492223
TI  - Scabies Mimicing Child Abuse - a Case Report.

PMID- 28492224
TI  - Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine
      inhibits osteoarthritis progression.
AB  - Osteoarthritis (OA) is characterized by cartilage destruction and chondrocytes
      have a central role in this process. With age and inflammation chondrocytes have
      reduced capacity to synthesize and maintain ATP, a molecule important for
      cartilage homeostasis. Here we show that concentrations of ATP and adenosine, its
      metabolite, fall after treatment of mouse chondrocytes and rat tibia explants
      with IL-1beta, an inflammatory mediator thought to participate in OA
      pathogenesis. Mice lacking A2A adenosine receptor (A2AR) or ecto-5'nucleotidase
      (an enzyme that converts extracellular AMP to adenosine) develop spontaneous OA
      and chondrocytes lacking A2AR develop an 'OA phenotype' with increased expression
      of Mmp13 and Col10a1. Adenosine replacement by intra-articular injection of
      liposomal suspensions containing adenosine prevents development of OA in rats.
      These results support the hypothesis that maintaining extracellular adenosine
      levels is an important homeostatic mechanism, loss of which contributes to the
      development of OA; targeting adenosine A2A receptors might treat or prevent OA.

PMID- 28492225
TI  - High-efficiency and high-power rechargeable lithium-sulfur dioxide batteries
      exploiting conventional carbonate-based electrolytes.
AB  - Shedding new light on conventional batteries sometimes inspires a chemistry
      adoptable for rechargeable batteries. Recently, the primary lithium-sulfur
      dioxide battery, which offers a high energy density and long shelf-life, is
      successfully renewed as a promising rechargeable system exhibiting small
      polarization and good reversibility. Here, we demonstrate for the first time that
      reversible operation of the lithium-sulfur dioxide battery is also possible by
      exploiting conventional carbonate-based electrolytes. Theoretical and
      experimental studies reveal that the sulfur dioxide electrochemistry is highly
      stable in carbonate-based electrolytes, enabling the reversible formation of
      lithium dithionite. The use of the carbonate-based electrolyte leads to a
      remarkable enhancement of power and reversibility; furthermore, the optimized
      lithium-sulfur dioxide battery with catalysts achieves outstanding cycle
      stability for over 450 cycles with 0.2 V polarization. This study highlights the
      potential promise of lithium-sulfur dioxide chemistry along with the viability of
      conventional carbonate-based electrolytes in metal-gas rechargeable systems.

PMID- 28492226
TI  - Circulating tumour DNA sequence analysis as an alternative to multiple myeloma
      bone marrow aspirates.
AB  - The requirement for bone-marrow aspirates for genomic profiling of multiple
      myeloma poses an obstacle to enrolment and retention of patients in clinical
      trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is
      comparable to molecular profiling of myeloma using bone-marrow tumour cells. We
      report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used
      to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64
      cfDNA specimens from 53 myeloma patients to >20,000 * median coverage. This
      method includes a variant filtering algorithm that enables detection of tumour
      derived fragments present in cfDNA at allele frequencies as low as 0.25% (median
      3.2%, range 0.25-46%). Using LB-Seq analysis of 48 cfDNA specimens with matched
      bone-marrow data, we detect 49/51 likely somatic mutations, with subclonal
      hierarchies reflecting tumour profiling (96% concordance), and four additional
      mutations likely missed by bone-marrow testing (>98% specificity). Overall, LB
      Seq is a high fidelity adjunct to genetic profiling of bone-marrow in multiple
      myeloma.

PMID- 28492229
TI  - Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid.
AB  - Natural pH regulatory mechanisms can be overruled during several pathologies such
      as cancer, inflammation and ischaemia, leading to local pH changes in the human
      body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as
      hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1
      13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH
      unit in the physiological pH range. The long lifetime of the hyperpolarized
      signal enhancement enables monitoring of pH, independent of concentration,
      temperature, ionic strength and protein concentration. We show in vivo pH maps
      within rat kidneys and subcutaneously inoculated tumours derived from a mammary
      adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly
      present in the extracellular space. We suggest that ZA represents a reliable and
      non-invasive extracellular imaging sensor to localize and quantify pH, with the
      potential to improve understanding, diagnosis and therapy of diseases
      characterized by aberrant acid-base balance.

PMID- 28492228
TI  - Association between a common immunoglobulin heavy chain allele and rheumatic
      heart disease risk in Oceania.
AB  - The indigenous populations of the South Pacific experience a high burden of
      rheumatic heart disease (RHD). Here we report a genome-wide association study
      (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian
      countries. Stratifying by ancestry, we analysed genotyped and imputed variants in
      Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in
      three further ancestral groups: Polynesians, South Asians and Mixed or other
      populations (totalling 399 cases and 617 controls). We identify a novel
      susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a
      haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to
      the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4
      fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27
      1.61, P=4.1 * 10-9). These findings provide new insight into the role of germline
      variation in the IGH locus in disease susceptibility.

PMID- 28492230
TI  - Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity.
AB  - Inflammasomes regulate innate immune responses by facilitating maturation of
      inflammatory cytokines, interleukin (IL)-1beta and IL-18. NACHT, LRR and PYD
      domains-containing protein 7 (NALP7) is one inflammasome constituent, but little
      is known about its cellular handling. Here we show a mechanism for NALP7 protein
      stabilization and activation of the inflammasome by Toll-like receptor (TLR)
      agonism with bacterial lipopolysaccharide (LPS) and the synthetic acylated
      lipopeptide Pam3CSK4. NALP7 is constitutively ubiquitinated and recruited to the
      endolysosome for degradation. With TLR ligation, the deubiquitinase enzyme, STAM
      binding protein (STAMBP) impedes NALP7 trafficking to lysosomes to increase NALP7
      abundance. STAMBP deubiquitinates NALP7 and STAMBP knockdown abrogates LPS or
      Pam3CSK4-induced increases in NALP7 protein. A small-molecule inhibitor of STAMBP
      deubiquitinase activity, BC-1471, decreases NALP7 protein levels and suppresses
      IL-1beta release after TLR agonism. These findings describe a unique pathway of
      inflammasome regulation with the identification of STAMBP as a potential
      therapeutic target to reduce pro-inflammatory stress.

PMID- 28492231
TI  - PPKs mediate direct signal transfer from phytochrome photoreceptors to
      transcription factor PIF3.
AB  - Upon light-induced nuclear translocation, phytochrome (phy) sensory
      photoreceptors interact with, and induce rapid phosphorylation and consequent
      ubiquitin-mediated degradation of, transcription factors, called PIFs, thereby
      regulating target gene expression and plant development. Nevertheless, the
      biochemical mechanism of phy-induced PIF phosphorylation has remained ill
      defined. Here we identify a family of nuclear protein kinases, designated
      Photoregulatory Protein Kinases (PPK1-4; formerly called MUT9-Like Kinases
      (MLKs)), that interact with PIF3 and phyB in a light-induced manner in vivo.
      Genetic analyses demonstrate that the PPKs are collectively necessary for the
      normal light-induced phosphorylation and degradation of PIF3. PPK1 directly
      phosphorylates PIF3 in vitro, with a phosphosite pattern that strongly mimics the
      light-induced pattern in vivo. These data establish that the PPKs are directly
      involved in catalysing the photoactivated-phy-induced phosphorylation of PIF3 in
      vivo, and thereby are critical components of a transcriptionally centred
      signalling hub that pleiotropically regulates plant growth and development in
      response to multiple signalling pathways.

PMID- 28492235
TI  - Fast oxygen diffusion and iodide defects mediate oxygen-induced degradation of
      perovskite solar cells.
AB  - Methylammonium lead halide perovskites are attracting intense interest as
      promising materials for next-generation solar cells, but serious issues related
      to long-term stability need to be addressed. Perovskite films based on CH3NH3PbI3
      undergo rapid degradation when exposed to oxygen and light. Here, we report
      mechanistic insights into this oxygen-induced photodegradation from a range of
      experimental and computational techniques. We find fast oxygen diffusion into
      CH3NH3PbI3 films is accompanied by photo-induced formation of highly reactive
      superoxide species. Perovskite films composed of small crystallites show higher
      yields of superoxide and lower stability. Ab initio simulations indicate that
      iodide vacancies are the preferred sites in mediating the photo-induced formation
      of superoxide species from oxygen. Thin-film passivation with iodide salts is
      shown to enhance film and device stability. The understanding of degradation
      phenomena gained from this study is important for the future design and
      optimization of stable perovskite solar cells.

PMID- 28492234
TI  - Molecular basis for blue light-dependent phosphorylation of Arabidopsis
      cryptochrome 2.
AB  - Plant cryptochromes undergo blue light-dependent phosphorylation to regulate
      their activity and abundance, but the protein kinases that phosphorylate plant
      cryptochromes have remained unclear. Here we show that photoexcited Arabidopsis
      cryptochrome 2 (CRY2) is phosphorylated in vivo on as many as 24 different
      residues, including 7 major phosphoserines. We demonstrate that four closely
      related Photoregulatory Protein Kinases (previously referred to as MUT9-like
      kinases) interact with and phosphorylate photoexcited CRY2. Analyses of the
      ppk123 and ppk124 triple mutants and amiR4k artificial microRNA-expressing lines
      demonstrate that PPKs catalyse blue light-dependent CRY2 phosphorylation to both
      activate and destabilize the photoreceptor. Phenotypic analyses of these mutant
      lines indicate that PPKs may have additional substrates, including those involved
      in the phytochrome signal transduction pathway. These results reveal a mechanism
      underlying the co-action of cryptochromes and phytochromes to coordinate plant
      growth and development in response to different wavelengths of solar radiation in
      nature.

PMID- 28492232
TI  - Pemphigus.
AB  - Pemphigus is a group of IgG-mediated autoimmune diseases of stratified squamous
      epithelia, such as the skin and oral mucosa, in which acantholysis (the loss of
      cell adhesion) causes blisters and erosions. Pemphigus has three major subtypes:
      pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. IgG
      autoantibodies are characteristically raised against desmoglein 1 and desmoglein
      3, which are cell-cell adhesion molecules found in desmosomes. The sites of
      blister formation can be physiologically explained by the anti-desmoglein
      autoantibody profile and tissue-specific expression pattern of desmoglein
      isoforms. The pathophysiological roles of T cells and B cells have been
      characterized in mouse models of pemphigus and patients, revealing insights into
      the mechanisms of autoimmunity. Diagnosis is based on clinical manifestations and
      confirmed with histological and immunochemical testing. The current first-line
      treatment is systemic corticosteroids and adjuvant therapies, including
      immunosuppressive agents, intravenous immunoglobulin and plasmapheresis.
      Rituximab, a monoclonal antibody against CD20+ B cells, is a promising
      therapeutic option that may soon become first-line therapy. Pemphigus is one of
      the best-characterized human autoimmune diseases and provides an ideal paradigm
      for both basic and clinical research, especially towards the development of
      antigen-specific immune suppression treatments for autoimmune diseases.

PMID- 28492233
TI  - ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo.
AB  - Mammalian A-type proteins, ISCA1 and ISCA2, are evolutionarily conserved proteins
      involved in iron-sulfur cluster (Fe-S) biogenesis. Recently, it was shown that
      ISCA1 and ISCA2 form a heterocomplex that is implicated in the maturation of
      mitochondrial Fe4S4 proteins. Here we report that mouse ISCA1 and ISCA2 are Fe2S2
      containing proteins that combine all features of Fe-S carrier proteins. We use
      biochemical, spectroscopic and in vivo approaches to demonstrate that despite
      forming a complex, ISCA1 and ISCA2 establish discrete interactions with
      components of the late Fe-S machinery. Surprisingly, knockdown experiments in
      mouse skeletal muscle and in primary cultures of neurons suggest that ISCA1, but
      not ISCA2, is required for mitochondrial Fe4S4 proteins biogenesis. Collectively,
      our data suggest that cellular processes with different requirements for ISCA1,
      ISCA2 and ISCA1-ISCA2 complex seem to exist.

PMID- 28492236
TI  - Kondo blockade due to quantum interference in single-molecule junctions.
AB  - Molecular electronics offers unique scientific and technological possibilities,
      resulting from both the nanometre scale of the devices and their reproducible
      chemical complexity. Two fundamental yet different effects, with no classical
      analogue, have been demonstrated experimentally in single-molecule junctions:
      quantum interference due to competing electron transport pathways, and the Kondo
      effect due to entanglement from strong electronic interactions. Here we unify
      these phenomena, showing that transport through a spin-degenerate molecule can be
      either enhanced or blocked by Kondo correlations, depending on molecular
      structure, contacting geometry and applied gate voltages. An exact framework is
      developed, in terms of which the quantum interference properties of interacting
      molecular junctions can be systematically studied and understood. We prove that
      an exact Kondo-mediated conductance node results from destructive interference in
      exchange-cotunneling. Nonstandard temperature dependences and gate-tunable
      conductance peaks/nodes are demonstrated for prototypical molecular junctions,
      illustrating the intricate interplay of quantum effects beyond the single-orbital
      paradigm.

PMID- 28492237
TI  - Proline metabolism supports metastasis formation and could be inhibited to
      selectively target metastasizing cancer cells.
AB  - Metastases are the leading cause of mortality in patients with cancer. Metastasis
      formation requires cancer cells to adapt their cellular phenotype. However, how
      metabolism supports this adaptation of cancer cells is poorly defined. We use 2D
      versus 3D cultivation to induce a shift in the cellular phenotype of breast
      cancer cells. We discover that proline catabolism via proline dehydrogenase
      (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we
      link proline catabolism to in vivo metastasis formation. In particular, we find
      that PRODH expression and proline catabolism is increased in metastases compared
      to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is
      sufficient to impair formation of lung metastases in the orthotopic 4T1 and
      EMT6.5 mouse models, without adverse effects on healthy tissue and organ
      function. In conclusion, we discover that Prodh is a potential drug target for
      inhibiting metastasis formation.

PMID- 28492238
TI  - Association of oxygen uptake at ventilatory threshold with risk of incident
      hypertension: a long-term prospective cohort study.

PMID- 28492239
TI  - Reductions in blood pressure during a community-based overweight and obesity
      treatment in children and adolescents with prehypertension and hypertension.
AB  - Due to the pandemic of childhood obesity and thus obesity-related hypertension,
      improvements in treatment availability are needed. Hence, we investigated whether
      reductions in blood pressure (BP) would occur in children with overweight and
      obesity exhibiting prehypertension/hypertension during a community-based
      overweight and obesity treatment program, and if changes in body mass index (BMI)
      are associated with changes in BP. The study included 663 children aged 3-18
      years with a BMI ?85th percentile for sex and age that entered treatment from
      June 2012 to January 2015. Height, weight and BP were measured upon entry and
      every 3-6 months. BMI and BP s.d. scores (SDSs) were calculated according to sex
      and age, or sex, age and height. Prehypertension was defined as a BP SDS ?1.28
      and <1.65. Hypertension was defined as a BP SDS ?1.65. Upon entry, 52% exhibited
      prehypertension (11.9%) or exhibited hypertension (40.1%). After 12 months
      (range: 3-29) of treatment, 29.3% of the children with
      prehypertension/hypertension were normotensive. Children with systolic
      prehypertension/hypertension upon entry reduced their systolic BP SDSs by 0.31
      (95% confidence interval (CI): 0.70-0.83, P<0.0001). Children with diastolic
      prehypertension/hypertension upon entry reduced their diastolic BP SDSs by 0.78
      (95% CI: 0.78-0.86, P<0.0001). BMI SDS changes were positively associated with BP
      SDS changes (P<0.0001). Nonetheless, some children reduced BP SDSs while
      increasing their BMI SDSs, and prehypertension/hypertension developed in 23.3% of
      the normotensive children despite reductions in BMI SDSs (P<0.0001). These
      results suggest that community-based overweight and obesity treatment can reduce
      BP, and thus may help improve treatment availability.

PMID- 28492241
TI  - Tuning the effective spin-orbit coupling in molecular semiconductors.
AB  - The control of spins and spin to charge conversion in organics requires
      understanding the molecular spin-orbit coupling (SOC), and a means to tune its
      strength. However, quantifying SOC strengths indirectly through spin relaxation
      effects has proven difficult due to competing relaxation mechanisms. Here we
      present a systematic study of the g-tensor shift in molecular semiconductors and
      link it directly to the SOC strength in a series of high-mobility molecular
      semiconductors with strong potential for future devices. The results demonstrate
      a rich variability of the molecular g-shifts with the effective SOC, depending on
      subtle aspects of molecular composition and structure. We correlate the above g
      shifts to spin-lattice relaxation times over four orders of magnitude, from 200
      to 0.15 MUs, for isolated molecules in solution and relate our findings for
      isolated molecules in solution to the spin relaxation mechanisms that are likely
      to be relevant in solid state systems.

PMID- 28492242
TI  - Structure and interstitial iodide migration in hybrid perovskite methylammonium
      lead iodide.
AB  - Hybrid perovskites form an emerging family of exceptional light harvesting
      compounds. However, the mechanism underpinning their photovoltaic effect is still
      far from understood, which is impeded by a lack of clarity on their structures.
      Here we show that iodide ions in the methylammonium lead iodide migrate via
      interstitial sites at temperatures above 280 K. This coincides with temperature
      dependent static distortions resulting in pseudocubic local symmetry. Based on
      bond distance analysis, the migrating and distorted iodines are at lengths
      consistent with the formation of I2 molecules, suggesting a 2I-->I2+2e- redox
      couple. The actual formula of this compound is thus (CH3NH3)PbI3-2x(I2)x where
      x~0.007 at room temperature. A crucial feature of the tetragonal structure is
      that the methylammonium ions do not sit centrally in the A-site cavity, but
      disordered around two off-centre orientations that facilitate the interstitial
      ion migration via a gate opening mechanism.

PMID- 28492244
TI  - Quantum physics: Atomic envoy enables molecular control.

PMID- 28492240
TI  - Tau association with synaptic vesicles causes presynaptic dysfunction.
AB  - Tau is implicated in more than 20 neurodegenerative diseases, including
      Alzheimer's disease. Under pathological conditions, Tau dissociates from axonal
      microtubules and missorts to pre- and postsynaptic terminals. Patients suffer
      from early synaptic dysfunction prior to Tau aggregate formation, but the
      underlying mechanism is unclear. Here we show that pathogenic Tau binds to
      synaptic vesicles via its N-terminal domain and interferes with presynaptic
      functions, including synaptic vesicle mobility and release rate, lowering
      neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the
      vesicle binding domain still localize to the presynaptic compartment but do not
      impair synaptic function in fly neurons. Moreover, an exogenously applied
      membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau
      induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of
      Tau that may be part of the early pathology in various Tauopathies and could be
      exploited therapeutically.

PMID- 28492246
TI  - Corrigendum: Early onset of industrial-era warming across the oceans and
      continents.

PMID- 28492247
TI  - Interdisciplinary debate: Agree on definitions of synchrony.

PMID- 28492243
TI  - Identification of mouse cochlear progenitors that develop hair and supporting
      cells in the organ of Corti.
AB  - The adult mammalian cochlear sensory epithelium houses two major types of cells,
      mechanosensory hair cells and underlying supporting cells, and lacks regenerative
      capacity. Recent evidence indicates that a subset of supporting cells can
      spontaneously regenerate hair cells after ablation only within the first week
      postparturition. Here in vivo clonal analysis of mouse inner ear cells during
      development demonstrates clonal relationship between hair and supporting cells in
      sensory organs. We report the identification in mouse of a previously unknown
      population of multipotent stem/progenitor cells that are capable of not only
      contributing to the hair and supporting cells but also to other cell types,
      including glia, in cochlea undergoing development, maturation and repair in
      response to damage. These multipotent progenitors originate from Eya1-expressing
      otic progenitors. Our findings also provide evidence for detectable regenerative
      potential in the postnatal cochlea beyond 1 week of age.

PMID- 28492248
TI  - PhD supervisors: invest more time.

PMID- 28492251
TI  - Multi-phase volcanic resurfacing at Loki Patera on Io.
AB  - The Jovian moon Io hosts the most powerful persistently active volcano in the
      Solar System, Loki Patera. The interior of this volcanic, caldera-like feature is
      composed of a warm, dark floor covering 21,500 square kilometres surrounding a
      much cooler central 'island'. The temperature gradient seen across areas of the
      patera indicates a systematic resurfacing process, which has been seen to occur
      typically every one to three years since the 1980s. Analysis of past data has
      indicated that the resurfacing progressed around the patera in an anti-clockwise
      direction at a rate of one to two kilometres per day, and that it is caused
      either by episodic eruptions that emplace voluminous lava flows or by a
      cyclically overturning lava lake contained within the patera. However, spacecraft
      and telescope observations have been unable to map the emission from the entire
      patera floor at sufficient spatial resolution to establish the physical processes
      at play. Here we report temperature and lava cooling age maps of the entire
      patera floor at a spatial sampling of about two kilometres, derived from ground
      based interferometric imaging of thermal emission from Loki Patera obtained on 8
      March 2015 ut as the limb of Europa occulted Io. Our results indicate that Loki
      Patera is resurfaced by a multi-phase process in which two waves propagate and
      converge around the central island. The different velocities and start times of
      the waves indicate a non-uniformity in the lava gas content and/or crust bulk
      density across the patera.

PMID- 28492252
TI  - Artificial intelligence: A social spin on language analysis.

PMID- 28492253
TI  - Corrigendum: Adipose-derived circulating miRNAs regulate gene expression in other
      tissues.

PMID- 28492254
TI  - PhD supervisors: be better mentors.

PMID- 28492255
TI  - Asia's glaciers are a regionally important buffer against drought.
AB  - The high mountains of Asia-encompassing the Himalayas, the Hindu Kush, Karakoram,
      Pamir Alai, Kunlun Shan, and Tian Shan mountains-have the highest concentration
      of glaciers globally, and 800 million people depend in part on meltwater from
      them. Water stress makes this region vulnerable economically and socially to
      drought, but glaciers are a uniquely drought-resilient source of water. Here I
      show that these glaciers provide summer meltwater to rivers and aquifers that is
      sufficient for the basic needs of 136 million people, or most of the annual
      municipal and industrial needs of Pakistan, Tajikistan, Turkmenistan, Uzbekistan
      and Kyrgyzstan. During drought summers, meltwater dominates water inputs to the
      upper Indus and Aral river basins. Uncertainties in mountain precipitation are
      poorly known, but, given the magnitude of this water supply, predicted glacier
      loss would add considerably to drought-related water stress. Such additional
      water stress increases the risk of social instability, conflict and sudden,
      uncontrolled population migrations triggered by water scarcity, which is already
      associated with the large and rapidly growing populations and hydro-economies of
      these basins.

PMID- 28492256
TI  - Corrigendum: Photovoltage field-effect transistors.

PMID- 28492259
TI  - Evolution: Sole survivor of a once-diverse lineage.

PMID- 28492258
TI  - Preparation and coherent manipulation of pure quantum states of a single
      molecular ion.
AB  - Laser cooling and trapping of atoms and atomic ions has led to advances including
      the observation of exotic phases of matter, the development of precision sensors
      and state-of-the-art atomic clocks. The same level of control in molecules could
      also lead to important developments such as controlled chemical reactions and
      sensitive probes of fundamental theories, but the vibrational and rotational
      degrees of freedom in molecules pose a challenge for controlling their quantum
      mechanical states. Here we use quantum-logic spectroscopy, which maps quantum
      information between two ion species, to prepare and non-destructively detect
      quantum mechanical states in molecular ions. We develop a general technique for
      optical pumping and preparation of the molecule into a pure initial state. This
      enables us to observe high-resolution spectra in a single ion (CaH+) and coherent
      phenomena such as Rabi flopping and Ramsey fringes. The protocol requires a
      single, far-off-resonant laser that is not specific to the molecule, so many
      other molecular ions, including polyatomic species, could be treated using the
      same methods in the same apparatus by changing the molecular source. Combined
      with the long interrogation times afforded by ion traps, a broad range of
      molecular ions could be studied with unprecedented control and precision. Our
      technique thus represents a critical step towards applications such as precision
      molecular spectroscopy, stringent tests of fundamental physics, quantum computing
      and precision control of molecular dynamics.

PMID- 28492260
TI  - Hydrology: Asian glaciers are a reliable water source.

PMID- 28492261
TI  - Science struggles on in my ravaged country.

PMID- 28492262
TI  - The secret war against counterfeit science.

PMID- 28492264
TI  - Censorship of addiction research is an abuse of science.

PMID- 28492263
TI  - Report estimated quake death tolls to save lives.

PMID- 28492265
TI  - Science publishers try new tack to combat unauthorized paper sharing.

PMID- 28492266
TI  - Cell maps reveal fresh details on how the immune system fights cancer.

PMID- 28492267
TI  - Ghana telescope heralds first pan-African array.

PMID- 28492268
TI  - Beware the anti-science label.

PMID- 28492269
TI  - NIH grant limits rile biomedical research community.

PMID- 28492270
TI  - DIY gene engineering, an attack on Darwinism and a probe into Nazi science.

PMID- 28492271
TI  - Satellite images reveal gaps in global population data.

PMID- 28492272
TI  - Brainstorming is not the way to discuss scientific issues.

PMID- 28492274
TI  - Corrigendum: Structural basis of synaptic vesicle assembly promoted by alpha
      synuclein.

PMID- 28492276
TI  - Dust-wind interactions can intensify aerosol pollution over eastern China.
AB  - Eastern China has experienced severe and persistent winter haze episodes in
      recent years due to intensification of aerosol pollution. In addition to
      anthropogenic emissions, the winter aerosol pollution over eastern China is
      associated with unusual meteorological conditions, including weaker wind speeds.
      Here we show, based on model simulations, that during years with decreased wind
      speed, large decreases in dust emissions (29%) moderate the wintertime land-sea
      surface air temperature difference and further decrease winds by -0.06 (+/-0.05)
      m s-1 averaged over eastern China. The dust-induced lower winds enhance
      stagnation of air and account for about 13% of increasing aerosol concentrations
      over eastern China. Although recent increases in anthropogenic emissions are the
      main factor causing haze over eastern China, we conclude that natural emissions
      also exert a significant influence on the increases in wintertime aerosol
      concentrations, with important implications that need to be taken into account by
      air quality studies.

PMID- 28492277
TI  - Association study and expression analysis of CYP4A11 gene copy number variation
      in Chinese cattle.
AB  - The identification of copy number variations (CNVs) allow us to explore genomic
      polymorphisms. In recent years, significant progress in understanding CNVs has
      been made in studies of human and animals, however, association and expression
      studies of CNVs are still in the early stage. It was previously reported that the
      Cytochrome P-450 4A11 (CYP4A11) gene is located within a copy number variable
      region (CNVR) that encompasses quantitative trait loci (QTLs) for economic traits
      like meat quality and milk production. So, this study was performed to determine
      the presence of CYP4A11 CNV in six distinct cattle breeds, identify its
      relationship with growth, and explore the biological effects of gene expression.
      For three CYP4A11 CNV types, Normal was more frequent than Gain or Loss.
      Association analysis revealed a positive effect of CYP4A11 copy number on growth
      traits (P < 0.05). One-way analysis of variance (ANOVA) analysis revealed that
      more CYP4A11 copies increased the gene expression level. Moreover, overexpression
      of CYP4A11 in vitro revealed its effect on lipid deposit. The data provide
      evidence for the functional role of CYP4A11 CNV and provide the basis for future
      applications in cattle breeding.

PMID- 28492275
TI  - The transcriptional repressor complex FRS7-FRS12 regulates flowering time and
      growth in Arabidopsis.
AB  - Most living organisms developed systems to efficiently time environmental
      changes. The plant-clock acts in coordination with external signals to generate
      output responses determining seasonal growth and flowering time. Here, we show
      that two Arabidopsis thaliana transcription factors, FAR1 RELATED SEQUENCE 7
      (FRS7) and FRS12, act as negative regulators of these processes. These proteins
      accumulate particularly in short-day conditions and interact to form a complex.
      Loss-of-function of FRS7 and FRS12 results in early flowering plants with overly
      elongated hypocotyls mainly in short days. We demonstrate by molecular analysis
      that FRS7 and FRS12 affect these developmental processes in part by binding to
      the promoters and repressing the expression of GIGANTEA and PHYTOCHROME
      INTERACTING FACTOR 4 as well as several of their downstream signalling targets.
      Our data reveal a molecular machinery that controls the photoperiodic regulation
      of flowering and growth and offer insight into how plants adapt to seasonal
      changes.

PMID- 28492278
TI  - Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces
      Amphetamine-Induced Dopamine Release and Reinforcing Effects.
AB  - Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH
      addiction to date, there is urgent need for the identification of druggable
      targets that mediate the reinforcing action of this stimulant class. AMPH
      stimulated dopamine efflux is modulated by protein kinase C (PKC) activation.
      Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity.
      The only known CNS-permeant PKC inhibitor is the selective estrogen receptor
      modulator tamoxifen. In this study, we demonstrate that a tamoxifen analog, 6c,
      which more potently inhibits PKC than tamoxifen but lacks affinity for the
      estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine
      and reinforcement-related behavior. In rat striatal synaptosomes, 6c was almost
      fivefold more potent at inhibiting AMPH-stimulated dopamine efflux than
      [3H]dopamine uptake through the dopamine transporter (DAT). The compound did not
      compete with [3H]WIN 35,428 binding or affect surface DAT levels. Using
      microdialysis, direct accumbal administration of 1 MUM 6c reduced dopamine
      overflow in freely moving rats. Using LC-MS, we demonstrate that 6c is CNS
      permeant. Systemic treatment of rats with 6 mg/kg 6c either simultaneously or 18
      h prior to systemic AMPH administration reduced both AMPH-stimulated dopamine
      overflow and AMPH-induced locomotor effects. Finally, 18 h pretreatment of rats
      with 6 mg/kg 6c s.c. reduces AMPH-self administration but not food self
      administration. These results demonstrate the utility of tamoxifen analogs in
      reducing AMPH effects on dopamine and reinforcement-related behaviors and suggest
      a new avenue of development for therapeutics to reduce AMPH abuse.

PMID- 28492280
TI  - Male Dispersal Pattern in Golden Snub-nosed Monkey (Rhinopithecus roxellana) in
      Qinling Mountains and its Conservation Implication.
AB  - Golden snub-nosed monkey (Rhinopithecus roxellana) is one of the most endangered
      primate species found in China, exhibiting multilevel society consisting of
      several one-male-females together with their offspring units (OMU), and all-male
      units (AMU). Female dispersal patterns of the species within herd have been well
      documented, whereas those of the males within or between herds are still poorly
      understood. Our results based a long-term observation indicate that more than
      half of sub-adult males, and half of the deposed males that stayed a short period
      in OMU disperse between herds, three of them established their own OMU in new
      herd after the dispersal. Smaller number of the sub-adult and adult males,
      compared with adult females, stayed in natal herd, implying sub-adult males
      started dispersing and male-biased dispersal occurred between herds. High
      frequencies of resident males were wounded as their OUMs were taken over, and
      resident males co-operation defend bachelor males were found. Mating competition
      among males within the herd may have contributed to the scenarios of male-biased
      dispersal. The results also suggest that maintaining connection between isolated
      herds and establishing the corridors among the fragmented habitats for the
      species will greatly benefit increasing its gene flow and promoting conservation
      status.

PMID- 28492279
TI  - Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment
      Resistant Depression.
AB  - The antidepressant effects of ketamine are thought to depend on brain-derived
      neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to
      characterize the dose-related antidepressant effects of ketamine in patients with
      treatment-resistant depression drawn from a Chinese population predominately
      possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a
      double-blind, randomized, parallel-group, placebo-controlled trial of a single
      ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype:
      Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received
      mood ratings before infusion, after infusion, and for the subsequent 14 days.
      Plasma ketamine levels and BDNF genotypes were assessed. This study found a
      significant dose-related ketamine effect on scores on the Hamilton Depression
      Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on
      at least 2 days between days 2 and 5) also revealed a significant dose-related
      effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first
      report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine
      for treatment-resistant depression and the first to characterize ketamine effects
      in a genotyped Chinese population in which most (83%) patients possessed at least
      one copy of the lower functioning Met allele of the BDNF gene.

PMID- 28492281
TI  - C. elegans chromosomes connect to centrosomes by anchoring into the spindle
      network.
AB  - The mitotic spindle ensures the faithful segregation of chromosomes. Here we
      combine the first large-scale serial electron tomography of whole mitotic
      spindles in early C. elegans embryos with live-cell imaging to reconstruct all
      microtubules in 3D and identify their plus- and minus-ends. We classify them as
      kinetochore (KMTs), spindle (SMTs) or astral microtubules (AMTs) according to
      their positions, and quantify distinct properties of each class. While our light
      microscopy and mutant studies show that microtubules are nucleated from the
      centrosomes, we find only a few KMTs directly connected to the centrosomes.
      Indeed, by quantitatively analysing several models of microtubule growth, we
      conclude that minus-ends of KMTs have selectively detached and depolymerized from
      the centrosome. In toto, our results show that the connection between centrosomes
      and chromosomes is mediated by an anchoring into the entire spindle network and
      that any direct connections through KMTs are few and likely very transient.

PMID- 28492283
TI  - Super-diffusion of excited carriers in semiconductors.
AB  - The ultrafast spatial and temporal dynamics of excited carriers are important to
      understanding the response of materials to laser pulses. Here we use scanning
      ultrafast electron microscopy to image the dynamics of electrons and holes in
      silicon after excitation with a short laser pulse. We find that the carriers
      exhibit a diffusive dynamics at times shorter than 200 ps, with a transient
      diffusivity up to 1,000 times higher than the room temperature value, D0~30 cm2s
      1. The diffusivity then decreases rapidly, reaching a value of D0 roughly 500 ps
      after the excitation pulse. We attribute the transient super-diffusive behaviour
      to the rapid expansion of the excited carrier gas, which equilibrates with the
      environment in 100-150 ps. Numerical solution of the diffusion equation, as well
      as ab initio calculations, support our interpretation. Our findings provide new
      insight into the ultrafast spatial dynamics of excited carriers in materials.

PMID- 28492282
TI  - Accumulation of heme biosynthetic intermediates contributes to the antibacterial
      action of the metalloid tellurite.
AB  - The metalloid tellurite is highly toxic to microorganisms. Several mechanisms of
      action have been proposed, including thiol depletion and generation of hydrogen
      peroxide and superoxide, but none of them can fully explain its toxicity. Here we
      use a combination of directed evolution and chemical and biochemical approaches
      to demonstrate that tellurite inhibits heme biosynthesis, leading to the
      accumulation of intermediates of this pathway and hydroxyl radical. Unexpectedly,
      the development of tellurite resistance is accompanied by increased
      susceptibility to hydrogen peroxide. Furthermore, we show that the heme precursor
      5-aminolevulinic acid, which is used as an antimicrobial agent in photodynamic
      therapy, potentiates tellurite toxicity. Our results define a mechanism of
      tellurite toxicity and warrant further research on the potential use of the
      combination of tellurite and 5-aminolevulinic acid in antimicrobial therapy.

PMID- 28492286
TI  - Has the SPRINT trial introduced a new blood-pressure goal in hypertension?
AB  - SPRINT is the first randomized, controlled trial showing that a systolic blood
      pressure goal of <120 mmHg can be attained with cardiovascular benefits in a
      select group of patients with hypertension and an elevated cardiovascular risk
      with different origins. Although the patient population with characteristics like
      those in SPRINT makes up only 20-30% of the total hypertensive population, SPRINT
      is a landmark study that highlights the need to consider lower blood- pressure
      goals in the treatment of hypertension. Extending this study to include other
      patient populations and geographical areas is the next step for evaluating the
      benefits of strict blood-pressure targets and the generalizability of the SPRINT
      results. Importantly, the blood-pressure measurement method used in SPRINT
      differs from previous clinical trials, and raises the issue of whether a more
      accurate method should be used in clinical trials and if such method is feasible
      in clinical practice. This Perspectives article provides an analysis of the
      SPRINT data, focusing on patient characteristics, blood-pressure measurement
      method, and applicability of the SPRINT findings for future management
      guidelines.

PMID- 28492284
TI  - Inhibition of corticotropin-releasing hormone receptor 1 and activation of
      receptor 2 protect against colonic injury and promote epithelium repair.
AB  - Maternal separation (MS) in neonates can lead to intestinal injury. MS in
      neonatal mice disrupts mucosal morphology, induces colonic inflammation and
      increases trans-cellular permeability. Several studies indicate that intestinal
      epithelial stem cells are capable of initiating gut repair in a variety of injury
      models but have not been reported in MS. The pathophysiology of MS-induced gut
      injury and subsequent repair remains unclear, but communication between the brain
      and gut contribute to MS-induced colonic injury. Corticotropin-releasing hormone
      (CRH) is one of the mediators involved in the brain-gut axis response to MS
      induced damage. We investigated the roles of the CRH receptors, CRHR1 and CRHR2,
      in MS-induced intestinal injury and subsequent repair. To distinguish their
      specific roles in mucosal injury, we selectively blocked CRHR1 and CRHR2 with
      pharmacological antagonists. Our results show that in response to MS, CRHR1
      mediates gut injury by promoting intestinal inflammation, increasing gut
      permeability, altering intestinal morphology, and modulating the intestinal
      microbiota. In contrast, CRHR2 activates intestinal stem cells and is important
      for gut repair. Thus, selectively blocking CRHR1 and promoting CRHR2 activity
      could prevent the development of intestinal injuries and enhance repair in the
      neonatal period when there is increased risk of intestinal injury such as
      necrotizing enterocolitis.

PMID- 28492285
TI  - Prolonged intracellular accumulation of light-inducible nanoparticles in leukemia
      cells allows their remote activation.
AB  - Leukaemia cells that are resistant to conventional therapies are thought to
      reside in protective niches. Here, we describe light-inducible polymeric retinoic
      acid (RA)-containing nanoparticles (NPs) with the capacity to accumulate in the
      cytoplasm of leukaemia cells for several days and release their RA payloads
      within a few minutes upon exposure to blue/UV light. Compared to NPs that are not
      activated by light exposure, these NPs more efficiently reduce the clonogenicity
      of bone marrow cancer cells from patients with acute myeloid leukaemia (AML) and
      induce the differentiation of RA-low sensitive leukaemia cells. Importantly, we
      show that leukaemia cells transfected with light-inducible NPs containing RA can
      engraft into bone marrow in vivo in the proximity of other leukaemic cells,
      differentiate upon exposure to blue light and release paracrine factors that
      modulate nearby cells. The NPs described here offer a promising strategy for
      controlling distant cell populations and remotely modulating leukaemic niches.

PMID- 28492287
TI  - Dyslipidaemia: PCSK9 inhibitors and foamy monocytes in familial
      hypercholesterolaemia.

PMID- 28492289
TI  - Peripheral artery disease: Drug-coated balloon superior to standard balloon
      angioplasty.

PMID- 28492288
TI  - Epidemiology of heart failure with preserved ejection fraction.
AB  - Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical
      syndrome associated with poor quality of life, substantial health-care resource
      utilization, and premature mortality. We summarize the current knowledge
      regarding the epidemiology of HFpEF with a focus on community-based studies
      relevant to quantifying the population burden of HFpEF. Current data regarding
      the prevalence and incidence of HFpEF in the community as well as associated
      conditions and risk factors, risk of morbidity and mortality after diagnosis, and
      quality of life are presented. In the community, approximately 50% of patients
      with HF have HFpEF. Although the age-specific incidence of HF is decreasing, this
      trend is less dramatic for HFpEF than for HF with reduced ejection fraction
      (HFrEF). The risk of HFpEF increases sharply with age, but hypertension, obesity,
      and coronary artery disease are additional risk factors. After adjusting for age
      and other risk factors, the risk of HFpEF is fairly similar in men and women,
      whereas the risk of HFrEF is much lower in women. Multimorbidity is common in
      both types of HF, but slightly more severe in HFpEF. A majority of deaths in
      patients with HFpEF are cardiovascular, but the proportion of noncardiovascular
      deaths is higher in HFpEF than HFrEF.

PMID- 28492290
TI  - Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder
      and non-small cell lung cancers.
AB  - In recent years, immunotherapy has come to the forefront as a major development
      in cancer treatment. Evasion of the immune system by tumor cells has been
      identified as one of the hallmarks of cancer and multiple therapies have been
      developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a
      ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer
      cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell
      mediated immune response against cancer cells. Atezolizumab is a monoclonal
      antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby
      enhancing T-cell activity against tumor cells. Atezolizumab has been shown to be
      well tolerated with no dose-limiting toxicities in phase I trials. Atezolizumab
      was approved by the U.S. Food and Drug Administration in 2016 for the treatment
      of platinum-resistant metastatic non-small cell lung cancer (NSCLC) and
      urothelial cancer based on phase II and preliminary phase III studies that have
      shown significant improvement in objective response rate and median overall
      survival. There are 117 ongoing clinical trials of atezolizumab currently. Given
      its efficacy in NSCLC and urothelial carcinoma, atezolizumab holds much potential
      in the future of cancer therapeutics.

PMID- 28492291
TI  - Crisaborole: Phosphodiesterase inhibitor for treatment of atopic dermatitis.
AB  - Atopic dermatitis (AD) is an extremely common condition affecting as many as 10
      20% of children and 2-10% of adults. A particularly distressing symptom of AD is
      pruritus. One of the important aspects of AD is inflammation associated with
      increased activity of phosphodiesterase 4 (PDE4), resulting in decreased
      intracellular levels of cyclic adenosine monophosphate, which in turn causes
      increased production of inflammatory cytokines. Crisaborole was developed as a
      small-molecule, boron-based, selective PDE4 inhibitor that can be used topically.
      Clinical trials have demonstrated its efficacy in treating patients with mild to
      moderate AD, resulting in significant relief of pruritus. Unlike PDE4 inhibitors
      that act systemically, crisaborole does not cause significant gastrointestinal
      adverse effects. The most common adverse effect has been temporary stinging and
      burning in about 4% of patients upon application of the 2% ointment. To date
      there is no evidence of atrophy, telangiectasia or hypopigmentation resulting
      from its use. Crisaborole is the first topically applied PDE4 inhibitor to be
      approved by the FDA for use in AD.

PMID- 28492292
TI  - Olaratumab for the treatment of soft tissue sarcoma.
AB  - Soft tissue sarcoma represents about 1% of all solid malignancies. The standard
      chemotherapy regimens have included doxorubicin alone or in combination with
      other agents. Despite recent advances in treatment beyond first line - with the
      FDA approval of pazopanib, eribulin and trabectidin - overall survival for
      patients with metastatic disease remains in the region of 12-19 months.
      Olaratumab is a monoclonal antibody directed against platelet-derived growth
      factor receptor alpha (PDGFRalpha). It was studied in a phase Ib and randomized
      phase II study in combination with doxorubicin in patients with soft tissue
      sarcoma who previously had not received doxorubicin for metastatic disease. The
      results of the phase II study showed a statistically significant improvement in
      progression-free survival up to 6 months, and a more dramatic improvement in
      overall survival to 26.9 months. This is the first randomized trial to show a
      significant improvement in overall survival compared to doxorubicin alone. An
      ongoing phase III study has completed accrual and results are being analyzed.
      Olaratumab has been granted accelerated approval by the United States Food and
      Drug Administration. Ongoing trials are underway to further demonstrate the
      mechanism of action. This review will document the studies involved in the
      development of olaratumab in the treatment of soft tissue sarcomas.

PMID- 28492293
TI  - European Association of Urology - 32nd Annual Congress (March 24-28, 2017 -
      London, UK).
AB  - The European Association of Urology (EAU) Congress is Europe's biggest urological
      event and this year's meeting, in London, UK, brought together more than 13,000
      participants from over 100 countries to discuss the latest research in this
      field. With 5 days' worth of lectures, debates, learning courses, presentations
      and live surgeries the congress provided plenty of opportunity to learn from the
      1,400 experts presenting, as well as to network with international peers.

PMID- 28492294
TI  - Effect of remifentanil for general anesthesia on parturients and newborns
      undergoing cesarean section: a meta-analysis.
AB  - INTRODUCTION: The results presented by studies investigating the effect of
      remifentanil on both parturients and newborns during cesarean section differed
      significantly. Therefore, we performed a meta-analysis to estimate the effect of
      remifentanil on these patients. EVIDENCE ACQUISITION: Potentially eligible
      studies published before 15 March 2016 were searched through four databases
      including PubMed, SCOPUS, ISI web of knowledge and EBSCO. Weighted mean
      difference (WMD) or odds ratios (ORs) and the corresponding 95% confidence
      interval (CI) were applied to estimate the strength of relationship. EVIDENCE
      SYNTHESIS: A total number of seven randomized-controlled trials were included in
      this meta-analysis. The results showed that Apgar values at 1 min and 5 min were
      significantly lower in the infants of remifentanil-treated mothers, with the WMD
      and corresponding 95% CI of -0.835 (-1.515, -0.154) and -0.296 (-0.570, -0.021),
      respectively. The pH value of umbilical artery was significantly higher in the
      remifentanil group (WMD: 0.014, 95% CI: 0.002, 0.025). The highest and lowest
      systolic blood pressures were significantly lower in remifentanil-treated
      mothers, with the WMD and corresponding 95% CI of -18.913 (-34.468, -3.359) and 
      12.982 (-21.479, -4.485), respectively. CONCLUSIONS: Remifentanil shows potential
      value of maternal circulation response during general anesthesia, which reduces
      maternal blood pressure in response to intubation and surgery. However, whether
      it is beneficial for the neonate is still controversial. More randomized
      controlled trials with larger sample size are required to assess the adverse
      effects of remifentanil.

PMID- 28492295
TI  - Elderly versus non-elderly patients with intra-abdominal candidiasis in the ICU.
AB  - BACKGROUND: Intra-abdominal candidiasis (IAC) has a considerable cost in terms of
      mortality and morbidity. We sought to study the epidemiology, characteristics and
      outcome of elderly (>75 years old) versus non-elderly patients with IAC and risk
      factors for mortality in elderly patients. METHODS: Post-hoc analysis of a
      retrospective multinational cohort study over a 3-year period (2011-2013).
      RESULTS: Of 482 patients, 124 (25.7%) were elderly and 358 (74.3%) were non
      elderly. The mean age was 80.4+/-3.9 and 56.3+/-13.8 years, respectively. Fifty
      four of 124 (43.5%) and 75/358 (20.9%) died until the end of observation. The
      majority of isolates were Candida albicans. Echinocandins were the most
      prescribed initial agent. Elderly patients were more likely to have a higher
      APACHE II Score, and to suffer from chronic obstructive pulmonary disease and
      heart disease. Non-elderly patients were more likely to be treated with
      immunosuppressants and steroids, and to have received solid organ
      transplantation. Mortality was significantly higher in the elderly group.
      Regarding risk factors for mortality in elderly patients, non-survivors were more
      likely to be males, reoperated, develop septic shock, receive vasopressors,
      suffer from end-stage renal disease (ESRD), and have inadequate abdominal source
      control within 48 hours. They had a higher APACHE II Score and a higher number of
      acquired organ dysfunction. ESRD and inadequate abdominal source control were
      significantly associated with mortality. CONCLUSIONS: Factors independently
      predicting mortality in elderly patients with IAC were ESRD and inadequate
      abdominal source control. Elderlies were found to have more pulmonary and cardiac
      morbidities and had higher mortality than non-elderlies.

PMID- 28492296
TI  - Italian COnsensus in Neuroradiological Anesthesia (ICONA).
AB  - Anesthetic management of patients undergoing endovascular procedures for treating
      intracranial aneurysms or cerebrovascular malformations must consider a number of
      specific challenges, in addition to those associated with anesthesia for other
      specialties. In addition to maintenance of physiological stability, manipulation
      of systemic and cerebral hemodynamic parameters may be required to treat any
      sudden unexpected catastrophic neurological events. A multidisciplinary group
      including neuro- and pediatric anesthesiologists, interventional
      neuroradiologists, neurosurgeons, and a clinical methodologist contributed to
      this document. This consensus working group from 21 Italian institutions
      identified open questions regarding the best practices for management of
      anesthesia during endovascular neuroradiological procedures for intracranial
      aneurysms and cerebrovascular malformations, and addressed these by formulating
      practical consensus statements. At the first meeting in November 2015, nine key
      areas were identified regarding choice of anesthetic, patient monitoring,
      hemodynamic targets, postoperative care, and the management of neuromuscular
      blockade, anticoagulant and/or antiplatelet therapy, and special considerations
      for pediatric patients. Nine subgroups were established and a medical librarian
      performed literature searches in the Cochrane and MEDLINE/PubMed databases for
      each group. Groups drafted literature summaries and provisional responses in the
      form of candidate consensus statements based on evidence, when possible, and
      clinical experience, when this was lacking. Final wording was agreed at a meeting
      in April 2016 and where possible evidence was graded using United States
      Preventive Services Task Force criteria. Consensus (defined as >90% agreement)
      was based on evidence, clinical experience, clinician preference, feasibility in
      the Italian healthcare system, and cost/benefit considerations.

PMID- 28492297
TI  - Recent antiseizure medications in the Intensive Care Unit.
AB  - BACKGROUND: Seizures and status epilepticus (SE), both clinical and subclinical,
      are frequent in critically ill patients. The list of available antiseizure
      medications (ASMs) is expanding and now includes older and widely used drugs as
      well as more recent medications with a better safety and pharmacokinetics
      profile. METHODS: We review a selection of recent publications about the
      indications and administration of ASMs in critical care for the prophylaxis and
      treatment of seizures and SE, focusing on recent ASMs available as intravenous
      formulation and emphasizing pharmacokinetics and safety issues in relation to
      several aspects of critical illness. RESULTS: Levetiracetam, lacosamide and more
      recently brivaracetam, represent interesting alternatives to older ASMs, mostly
      due to a more favorable safety and pharmacokinetic profile. Low-quality studies
      suggest that this profile results in better tolerability in treated patients.
      Ketamine might represent a useful addition in our anesthetic armamentarium for
      refractory SE, due to its different mechanism of action and cardiovascular
      properties. Little evidence is available however to support the prophylactic use
      of ASMs in critically ill patients, except in specific settings (traumatic brain
      injury and subarachnoid hemorrhage). Head-to-head studies comparing recent and
      older ASMs in the treatment of acute seizures and SE are ongoing or awaiting
      publication. Administration of ASMs to critically ill patients needs to be
      adapted to organ dysfunction, and especially to renal dysfunction for recent
      drugs. CONCLUSIONS: Recent ASMs and could represent better treatment choices in
      critically ill patients than older ones but this needs to be confirmed in
      randomized controlled studies. In general, further studies are required to
      clarify the indications and optimal use of ASMs in the critical care setting.

PMID- 28492298
TI  - Use of the ultrasound-guided erector spinae plane block in breast surgery.

PMID- 28492299
TI  - Extraglottic airway devices and ultrasound airway evaluation: are we on the right
      track?

PMID- 28492300
TI  - Rational Design and Construction of Well-Organized Macro-Mesoporous SiO2/TiO2
      Nanostructure toward Robust High-Performance Self-Cleaning Antireflective Thin
      Films.
AB  - Antireflection (AR) thin films on optical substrates are of great significance in
      high-performance optoelectronic devices. Here, we present a rational design and
      construction of well-organized macro-mesoporous nanostructure toward robust high
      performance self-cleaning antireflective thin films on the basis of effective
      medium theory and finite difference time domain (FDTD) simulations that combine
      the optical design principle. A hierarchical macro-mesoporous SiO2 thin film with
      very high porosity and gradient refractive indexes works as a lambda/4-wavelength
      AR layer and significantly suppresses the reflection in the range from 350 to
      1200 nm. Even after dip-coating a layer of high refractive index TiO2
      nanocrystals, the nanostructured thin film still exhibits broadband AR properties
      which are much superior to conventional flat SiO2/TiO2 thin films, especially in
      the range of 350-500 nm. In addition, the obtained thin film exhibits
      photocatalytic self-cleaning and durable superhydrophilicity. The advantages
      brought by the well-organized macro-mesoporous structure are also testified
      through comparing to the solely mesoporous SiO2/TiO2 film counterpart. Moreover,
      the pencil hardness test and sandpaper abrasion test show favorable robustness
      and functional durability of the thin film, which make it extremely attractive
      for practical applications in optical devices, display devices, and photovoltaic
      cells.

PMID- 28492301
TI  - High-Affinity RGD-Knottin Peptide as a New Tool for Rapid Evaluation of the
      Binding Strength of Unlabeled RGD-Peptides to alphavbeta3, alphavbeta5, and
      alpha5beta1 Integrin Receptors.
AB  - We describe a highly sensitive competition ELISA to measure integrin-binding of
      RGD-peptides in high-throughput without using cells, ECM-proteins, or antibodies.
      The assay measures (nonlabeled) RGD-peptides' ability to inhibit binding of a
      biotinylated "knottin"-RGD peptide to surface-immobilized integrins and, thus,
      enables quantification of the binding strength of high-, medium-, and low
      affinity RGD-binders. We introduced the biotinylated knottin-RGD peptide instead
      of biotinylated cyclo[RGDfK] (as reported by Piras et al.), as integrin-binding
      was much stronger and clearly detectable for all three integrins. In order to
      maximize sensitivity and cost-efficiency, we first optimized several parameters,
      such as integrin-immobilization levels, knottin-RGD concentration, buffer
      compositions, type of detection tag (biotin, His- or cMyc-tag), and spacer
      length. We thereby identified two key factors, that is, (i) the critical spacer
      length (longer than Gly) and (ii) the presence of Ca2+ and Mg2+ in all incubation
      and washing buffers. Binding of knottin-RGD peptide was strongest for alphavbeta3
      but also detectable for both alphavbeta5 and alpha5beta1, while binding of
      biotinylated cyclo[RGDfK] was very weak and only detectable for alphavbeta3. For
      assay validation, we finally determined IC50 values for three unlabeled peptides,
      that is: (i) linear GRGDS, (ii) cyclo[RGDfK], and (iii) the knottin-RGD itself
      for binding to three different integrin receptors (alphavbeta3, alphavbeta5,
      alpha5beta1). Major benefits of the novel assay are (i) the extremely low
      consumption of integrin (50 ng/peptide), (ii) the fact that neither
      antibodies/ECM-proteins nor integrin-expressing cells are required for detection,
      and (iii) its suitability for high-throughput screening of (RGD-)peptide
      libraries.

PMID- 28492302
TI  - Metal-Organic Framework Templated Catalysts: Dual Sensitization of PdO-ZnO
      Composite on Hollow SnO2 Nanotubes for Selective Acetone Sensors.
AB  - Metal-organic framework (MOF)-derived synergistic catalysts were easily
      functionalized on hollow SnO2 nanotubes (NTs) via electrospinning and subsequent
      calcination. Nanoscale Pd NPs (~2 nm) loaded Zn-based zeolite imidazole framework
      (Pd@ZIF-8, ~80 nm) was used as a new catalyst-loading platform for the effective
      functionalization of a PdO@ZnO complex catalyst onto the thin wall of one
      dimensional metal oxide NTs. The well-dispersed nanoscale PdO catalysts (3-4 nm)
      and multiheterojunctions (PdO/ZnO and ZnO/SnO2) on hollow structures are
      essential for the development of high-performance gas sensors. As a result, the
      PdO@ZnO dual catalysts-loaded hollow SnO2 NTs (PdO@ZnO-SnO2 NTs) exhibited high
      acetone response (Rair/Rgas = 5.06 at 400  degrees C @ 1 ppm), superior acetone
      selectivity against other interfering gases, and fast response (20 s) and
      recovery (64 s) time under highly humid atmosphere (95% RH). In this work, the
      advantages of hollow SnO2 NT structures with high surface area and open porosity
      were clearly demonstrated by the comparison to SnO2 nanofibers (NFs). Moreover,
      the sensor arrays composed of SnO2 NFs, SnO2 NTs, PdO@ZnO-SnO2 NFs, and PdO@ZnO
      SnO2 NTs successfully identified the patterns of the exhaled breath of normal
      people and simulated diabetics by using a principal component analysis.

PMID- 28492303
TI  - A Unique "Integration" Strategy for the Rational Design of Optically Tunable Near
      Infrared Fluorophores.
AB  - Fluorescence imaging is a rapidly growing technique for noninvasive imaging of
      biological molecules and processes with high spatial and temporal resolution. For
      effective biological imaging, it is essential and important to develop robust
      fluorescent dyes, in particular, near-infrared (NIR) fluorescent dyes with
      favorable optical properties. Compared with the visible light emitting dyes, NIR
      dyes have relatively longer emission wavelengths (650-900 nm) with lower energy
      and are advantageous as imaging agents owing to the minimum photodamage of NIR
      light to biological samples, deep penetration into tissues, and low interference
      from autofluorescence of biomolecules. Although great efforts have been devoted
      to engineer NIR fluorophores, it is still very challenging to regulate their
      photophysical properties as they often lack optically tunable mechanisms, and
      this shortcoming considerably restricts the realization of their full potential.
      Consequently, the rational design of small-molecule optically tunable NIR
      fluorophores is of high priority and great value. In general, two key
      characteristics are indispensable for designing excellent optically tunable NIR
      fluorescent dyes. First, NIR fluorescent dyes should display the maximal
      absorption and emission located in the NIR region and also have the prominent
      properties including excellent fluorescence quantum yields, large Stokes shifts,
      good chemical stability and photostability, low cytotoxicity, and desirable
      compatibility with biological systems. Second, in principle, functional NIR dyes
      should also possess optically tunable groups, which can be easily modified to
      afford responsive sites for the targets of interest. With these considerations in
      mind, in this Account, we described a unique "integration" strategy for judicious
      design of the optically tunable NIR fluorophores, which are an intuitive
      combination of the traditional NIR dyes and the optically tunable mechanisms in
      the visible light emissive dyes. Thus, the versatile strategy may allow not only
      retention of the NIR emission properties of NIR dyes but also inheritance of the
      optically tunable mechanisms from the visible light emissive dyes. By the unique
      integration strategy, a built-in optically tunable group is strategically
      installed into the traditional NIR fluorescent dyes to directly tune their
      optical properties. Herein, we present a concise review of the rational design
      strategy and biological applications of small-molecule optically tunable NIR
      fluorescent dyes via the unique integration strategy, and we focused mainly on
      our work and some representative examples from other groups based on our NIR
      platforms. This Account includes the detailed integration strategy of each class
      of the NIR fluorescent dyes, the development of their derivatives, and their
      imaging applications in living systems.

PMID- 28492304
TI  - Deep-Red Fluorescent Gold Nanoclusters for Nucleoli Staining: Real-Time
      Monitoring of the Nucleolar Dynamics in Reverse Transformation of Malignant
      Cells.
AB  - Nucleoli are important subnuclear structures inside cells. We report novel
      fluorescent gold nanoclusters (K-AuNCs) that are able to stain the nucleoli
      selectively and make it possible to explore the nucleolar morphology with
      fluorescence imaging technique. This novel probe is prepared through an easy
      synthesis method by employing a tripeptide (Lys-Cys-Lys) as the surface ligand.
      The properties, including deep-red fluorescence emission (680 nm), large Stocks
      shift, broad excitation band, low cytotoxicity, and good photostability, endow
      this probe with potential for bioanalytical applications. Because of their small
      size and their positively charged surface, K-AuNCs are able to accumulate
      efficiently at the nucleolar regions and provide precise morphological
      information. K-AuNCs are also used to monitor the nucleolar dynamics along the
      reverse-transformation process of malignant cells, induced by the agonist of
      protein A, 8-chloro-cyclic adenosine monophosphate. This gives a novel approach
      for investigating the working mechanism of antitumor drugs.

PMID- 28492305
TI  - Monitoring Interfacial Lipid Oxidation in Oil-in-Water Emulsions Using Spatially
      Resolved Optical Techniques.
AB  - The oxidation of lipids is an important phenomenon with ramifications for
      disciplines that range from food science to cell biology. The development and
      characterization of tools and techniques to monitor lipid oxidation are thus
      relevant. Of particular significance in this regard are tools that facilitate the
      study of oxidations at interfaces in heterogeneous samples (e.g., oil-in-water
      emulsions, cell membranes). In this article, we establish a proof-of-principle
      for methods to initiate and then monitor such oxidations with high spatial
      resolution. The experiments were performed using oil-in-water emulsions of
      polyunsaturated fatty acids (PUFAs) prepared from cod liver oil. We produced
      singlet oxygen at a point near the oil-water interface of a given PUFA droplet in
      a spatially localized two-photon photosensitized process. We then followed the
      oxidation reactions initiated by this process with the fluorescence-based imaging
      technique of structured illumination microscopy (SIM). We conclude that the
      approach reported herein has attributes well-suited to the study of lipid
      oxidation in heterogeneous samples.

PMID- 28492306
TI  - Large Lateral Photovoltage Observed in MoS2 Thickness-Modulated ITO/MoS2/p-Si
      Heterojunctions.
AB  - Molybdenum disulfide (MoS2), as a typical two-dimensional (2D) material, has
      attracted extensive attention in recent years because of its fascinating optical
      and electric properties. However, the applications of MoS2 have been mainly in
      photovoltaic devices, field-effect transistors, photodetectors, and gas sensors.
      Here, it is demonstrated that MoS2 can be found another important application in
      position sensitive detector (PSD) based on lateral photovoltaic effect (LPE) in
      it. The ITO/MoS2(3, 5, 7, 9, 10, 20, 50, 100 nm)/p-Si heterojunctions were
      successfully prepared with vertically standing nanosheet structure of MoS2.
      Because of the special structure and the strong light absorption of the
      relatively thick MoS2 film, the ITO/MoS2/p-Si heterojunction exhibits an abnormal
      thickness-dependent LPE, which can be ascribed to the n- to p-type transformation
      of MoS2. Moreover, the LPE of ITO/MoS2/p-Si structure improves greatly because of
      forward enhanced built-in field by type transformation in a wide spectrum
      response ranging from visible to near-infrared, especially the noticeable
      improvement in infrared region, indicating its great potential application in
      infrared PSDs. This work not only suggest that the ITO/MoS2/p-Si heterojunction
      shows great potential in LPE-based sensors, but also unveils the importance of
      type transformation of MoS2 in MoS2-based photoelectric devices besides strong
      light absorption and suitable bandgap.

PMID- 28492307
TI  - Sensitive Quantification of MicroRNAs by Isothermal Helicase-Dependent
      Amplification.
AB  - Dysregulation of microRNA expression levels is closely associated with a variety
      of human diseases, and their rapid and sensitive quantification is essential to
      clinical diagnosis and therapy. Because of their poor sensitivity, conventional
      quantification methods are unable to detect low-abundance microRNAs.
      Alternatively, nucleic acid amplification approaches have been introduced to
      improve the detection sensitivity, but most of them involve complicated probe
      design and time-consuming procedures. Herein, we report a simple, rapid, and
      sensitive fluorescent method for label-free detection of low-abundance microRNAs
      based on isothermal helicase-dependent amplification. In this assay, the target
      microRNA may specifically hybridize with the 3'-terminus of the linear probe to
      form a DNA-microRNA heteroduplex, protecting the probes from exonuclease I
      digestion. The remaining probes may be subsequently amplified by helicase
      dependent amplification, generating an ultrahigh fluorescence signal within 30
      min. This assay is very sensitive with a low detection limit of 12.8 fM and
      exhibits a large dynamical range from 100 fM to 10 nM. Moreover, this assay can
      discriminate different microRNA family members, and it can be used to absolutely
      quantify endogenous microRNA of total RNA samples extracted from cancer cells,
      providing a powerful tool for biomedical research and clinical diagnostics.

PMID- 28492308
TI  - Visualizing the Conversion Process of Alcohol-Induced Fatty Liver to
      Steatohepatitis in Vivo with a Fluorescent Nanoprobe.
AB  - Excess alcohol consumption and the associated development of alcoholic liver
      disease (ALD) are major public health challenges worldwide. Since patients with
      the severe stages of ALD no longer benefit from clinical therapies, early warning
      of ALD holds significant promise for increasing the cure rate of ALD. Herein, we
      develop a bicolor fluorescent nanoprobe for dynamically monitoring the conversion
      process of alcohol-induced fatty liver to steatohepatitis in vivo through
      simultaneous imaging of microRNA 155 and osteopontin mRNA, which are related to
      fatty liver and steatohepatitis, respectively. The fluorescence imaging results
      indicate that the nanoprobe can effectively differentiate alcohol-induced fatty
      liver and steatohepatitis. Moreover, the nanoprobe can monitor the transmutation
      process of alcohol-induced fatty liver to steatohepatitis and assess the
      remission effects of N-acetyl cysteine for alcohol-induced liver injury. We
      anticipate the developed nanoprobe and imaging method can provide new ways for
      early warning, treatments, and prognosis of ALD.

PMID- 28492309
TI  - Competitive Inhibition Mechanism of Acetylcholinesterase without Catalytic Active
      Site Interaction: Study on Functionalized C60 Nanoparticles via in Vitro and in
      Silico Assays.
AB  - Acetylcholinesterase (AChE) activity regulation by chemical agents or,
      potentially, nanomaterials is important for both toxicology and pharmacology.
      Competitive inhibition via direct catalytic active sites (CAS) binding or
      noncompetitive inhibition through interference with substrate and product
      entering and exiting has been recognized previously as an AChE-inhibition
      mechanism for bespoke nanomaterials. The competitive inhibition by peripheral
      anionic site (PAS) interaction without CAS binding remains unexplored. Here, we
      proposed and verified the occurrence of a presumed competitive inhibition of AChE
      without CAS binding for hydrophobically functionalized C60 nanoparticles (NPs) by
      employing both experimental and computational methods. The kinetic inhibition
      analysis distinguished six competitive inhibitors, probably targeting the PAS,
      from the pristine and hydrophilically modified C60 NPs. A simple quantitative
      nanostructure-activity relationship (QNAR) model relating the pocket accessible
      length of substituent to inhibition capacity was then established to reveal how
      the geometry of the surface group decides the NP difference in AChE inhibition.
      Molecular docking identified the PAS as the potential binding site interacting
      with the NPs via a T-shaped plug-in mode. Specifically, the fullerene core
      covered the enzyme gorge as a lid through pi-pi stacking with Tyr72 and Trp286 in
      the PAS, while the hydrophobic ligands on the fullerene surface inserted into the
      AChE active site to provide further stability for the complexes. The modeling
      predicted that inhibition would be severely compromised by Tyr72 and Trp286
      deletions, and the subsequent site-directed mutagenesis experiments proved this
      prediction. Our results demonstrate AChE competitive inhibition of NPs without
      CAS participation to gain further understanding of both the neurotoxicity and the
      curative effect of NPs.

PMID- 28492310
TI  - Raster-Mode Continuous-Flow Liquid Microjunction Mass Spectrometry Imaging of
      Proteins in Thin Tissue Sections.
AB  - Mass spectrometry imaging by use of continuous-flow liquid microjunction sampling
      at discrete locations (array mode) has previously been demonstrated. In this
      Letter, we demonstrate continuous-flow liquid microjunction mass spectrometry
      imaging of proteins from thin tissue sections in raster mode and discuss
      advantages (a 10-fold reduction in analysis time) and challenges (suitable
      solvent systems, data interpretation) of the approach. Visualization of data is
      nontrivial, requiring correlation of solvent-flow, mass spectral data acquisition
      rate, data quality, and liquid microjunction sampling area. The latter is
      particularly important for determining optimum pixel size. The minimum achievable
      pixel size is related to the scan time of the instrument used. Here we show a
      minimum achievable pixel size of 50 MUm (x-dimension) when using an Orbitrap
      Elite; however a pixel size of 600 MUm is recommended in order to minimize the
      effects of oversampling on image accuracy.

PMID- 28492311
TI  - Pressure-Sensitive and Conductive Carbon Aerogels from Poplars Catkins for
      Selective Oil Absorption and Oil/Water Separation.
AB  - Multifunctional carbon aerogels that are both highly compressible and conductive
      have broad potential applications in the range of sound insulator, sensor, oil
      absorption, and electronics. However, the preparation of such carbon aerogels has
      been proven to be very challenging. Here, we report fabrication of pressure
      sensitive and conductive (PSC) carbon aerogels by pyrolysis of cellulose aerogels
      composed of poplars catkin (PC) microfibers with a tubular structure. The wet PC
      gels can be dried directly in an oven without any deformation, in marked contrast
      to the brittle nature of traditional carbon aerogels. The resultant PSC aerogels
      exhibit ultralow density (4.3 mg cm-3), high compressibility (80%), high
      electrical conductivity (0.47 S cm-1), and high absorbency (80-161 g g-1) for
      oils and organic liquids. The PSC aerogels have potential applications in various
      fields such as elastomeric conductors, absorption of oils from water and
      oil/water separation, as the PSC aerogels feature simple preparation process with
      low-cost biomass as the precursor.

PMID- 28492312
TI  - Synthesis and Characterization of Graphene Oxide-Polystyrene Composite Capsules
      with Aqueous Cargo via a Water-Oil-Water Multiple Emulsion Templating Route.
AB  - Graphene oxide/polystyrene (GO/PS) nanocomposite capsules containing a two
      compartment cargo have been successfully fabricated using a Pickering emulsion
      strategy. Highly purified GO sheets with typically micrometer-scale lateral
      dimensions and amphiphilic characteristics were prepared from the oxidation
      reaction of graphite with concomitant exfoliation of the graphite structure.
      These GO sheets were employed as a stabilizer for oil-in-water emulsions where
      the oil phase comprised toluene or olive oil. The stability and morphology of the
      emulsions were extensively studied as a function of different parameters
      including GO concentration, aqueous phase pH, ultrasonication time, effects of
      added electrolytes and stability to dilution. In selected conditions, the olive
      oil emulsions showed spontaneous formation of multiple w/o/w emulsions with high
      stability, whereas toluene formed simple o/w emulsions of lower overall
      stability. Olive oil emulsions were therefore used to prepare capsules templated
      from emulsion droplets by surrounding the oil phase with a GO/PS shell. The GO
      sheets, emulsions and composite capsules were characterized using a variety of
      physical and spectroscopic techniques in order to unravel the interactions
      responsible for capsule formation. The ability of the capsules to control the
      release of a model active agent in the form of a hydrophilic dye was explored,
      and release kinetics were monitored using UV-visible spectroscopy to obtain rate
      parameters. The composite capsules showed promising sustained release properties,
      with release rates 11* lower than the precursor GO-stabilized multiple emulsion
      droplets.

PMID- 28492314
TI  - The Synthesis of Chiral beta,beta-Diaryl Allylic Alcohols and Their Use in the
      Preparation of alpha-Tertiary Allylamines and Quaternary alpha-Amino Acids.
AB  - An approach to nonracemic beta,beta-diarylsubstituted allyl alcohols is
      described. Their synthesis starts from l-lactic acid-derived propargyl alcohol,
      which is submitted to sequential Sonogashira/Suzuki or Sonagashira/Stille
      coupling reactions. Both approaches enable the synthesis of either (Z)- or (E)
      allylic alcohols regarding the order of introducing coupling agents. The obtained
      allyl alcohols were applied in the synthesis of nonracemic alpha-tertiary
      allylamines via stereocontrolled cyanate-to-isocyanate sigmatropic rearrangement
      reactions of the corresponding allyl carbamates. The stereoselectivity of the
      process is controlled by the geometry of the double bond of the starting allyl
      derivative. As demonstrated, a rearrangement of (S,Z)-allyl carbamates provides
      (S)-teriary allylamines, whereas the transformation (S,E)-isomers leads to (R)
      allylamines.

PMID- 28492313
TI  - Size, Composition, and Source Profiles of Inhalable Bioaerosols from Colorado
      Dairies.
AB  - Particulate matter emissions from agricultural livestock operations contain both
      chemical and biological constituents that represent a potential human health
      hazard. The size and composition of these dusts, however, have not been well
      described. We evaluated the full size distribution (from 0 to 100 MUm in
      aerodynamic diameter) and chemical/biological composition of inhalable dusts
      inside several Colorado dairy parlors. Four aerodynamic size fractions (<3, 3-10,
      10-30, and >30 MUm) were collected and analyzed using a combination of
      physiochemical techniques to understand the structure of bacterial communities
      and chemical constituents. Airborne particulate mass followed a bimodal size
      distribution (one mode at 3 MUm and a second above 30 MUm), which also correlated
      with the relative concentrations of the following microbiological markers:
      bacterial endotoxin, 3-hydroxy fatty acids, and muramic acid. Sequencing of the
      16S-rRNA components of this aerosol revealed a microbiome derived predominantly
      from animal sources. Bacterial genera included Staphlyococcus, Pseudomonas, and
      Streptococcus, all of which have proinflammatory and pathogenic capacity. Our
      results suggest that the size distribution of bioaerosols emitted by dairy
      operations extends well above 10 MUm in diameter and contains a diverse mixture
      of potentially hazardous constituents and opportunistic pathogens. These findings
      should inform the development of more effective emissions control strategies.

PMID- 28492315
TI  - Missing Food, Missing Data? A Critical Review of Global Food Losses and Food
      Waste Data.
AB  - Food losses and food waste (FLW) have become a global concern in recent years and
      emerge as a priority in the global and national political agenda (e.g., with
      Target 12.3 in the new United Nations Sustainable Development Goals). A good
      understanding of the availability and quality of global FLW data is a
      prerequisite for tracking progress on reduction targets, analyzing environmental
      impacts, and exploring mitigation strategies for FLW. There has been a growing
      body of literature on FLW quantification in the past years; however, significant
      challenges remain, such as data inconsistency and a narrow temporal,
      geographical, and food supply chain coverage. In this paper, we examined 202
      publications which reported FLW data for 84 countries and 52 individual years
      from 1933 to 2014. We found that most existing publications are conducted for a
      few industrialized countries (e.g., the United Kingdom and the United States),
      and over half of them are based only on secondary data, which signals high
      uncertainties in the existing global FLW database. Despite these uncertainties,
      existing data indicate that per-capita food waste in the household increases with
      an increase of per-capita GDP. We believe that more consistent, in-depth, and
      primary-data-based studies, especially for emerging economies, are badly needed
      to better inform relevant policy on FLW reduction and environmental impacts
      mitigation.

PMID- 28492316
TI  - Environmentally Persistent Free Radicals in Soils of Past Coking Sites:
      Distribution and Stabilization.
AB  - This study presents the existence of environmentally persistent free radicals
      (EPFRs) in soils of past coking sites, mainly contaminated by polycyclic aromatic
      hydrocarbons (PAHs). Measurements of EPFRs were conducted by electron
      paramagnetic resonance (EPR) technique with numerous soil samples, which were
      collected from different distances (0-1000 m) and different depths (0-30 cm) of
      three contaminant sources. EPR signals with ~3 * 1017 radicals/g of the soil
      samples were obtained, which are very similar to that generated in PAHs
      contaminated clays, that is, g = 2.0028-2.0036. Concentrations of PAHs and soil
      components were determined to understand their role in producing EPFRs. PAHs,
      clay, and iron predominately contributed to generating EPRFs. Meanwhile, organic
      matter negatively influenced the production of EPRFs. The effects of
      environmental factors (moisture and oxic/anoxic) were also studied to probe the
      persistency of EPFRs under various simulated conditions. The EPFRs are stable
      under relatively dry and oxic conditions. Under anoxic conditions without O2 and
      H2O, the spin densities decrease initially, followed by gradual increase before
      attaining constant values in two months period time. The present work implies
      that continuous formation of EPFRs induced by PAHs is largely responsible for the
      presence of relatively stable radicals in soils of coking sites.

PMID- 28492317
TI  - Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular
      Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis
      Protein (XIAP).
AB  - XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and
      are key regulators of anti-apoptotic and pro-survival signaling pathways.
      Overexpression of IAPs occurs in various cancers and has been associated with
      tumor progression and resistance to treatment. Structure-based drug design (SBDD)
      guided by structural information from X-ray crystallography, computational
      studies, and NMR solution conformational analysis was successfully applied to a
      fragment-derived lead resulting in AT-IAP, a potent, orally bioavailable, dual
      antagonist of XIAP and cIAP1 and a structurally novel chemical probe for IAP
      biology.

PMID- 28492319
TI  - Zero in-Plane Thermal Expansion in Guest-Tunable 2D Coordination Polymers.
AB  - Zero in-plane thermal expansion (TE) in a two-dimensional (2D) coordination
      polymer is demonstrated. The combination of components that expand and those that
      shrink into zigzag layers results in no net area change in the 2D materials with
      temperature. Single crystals of [Mn(salen)]2[Mn(N)(CN)4(guest)] (salen = N,N'
      ethylenebis(salicylideneaminato), guest = MeOH and MeCN) were prepared, and
      variable-temperature single-crystal X-ray structural analyses demonstrated that
      these compounds exhibited both anisotropic positive and negative thermal
      expansion depending on the guest species. The TE behavior results from
      distortions of the octahedral coordination geometry of [Mn(salen)]+ units in the
      zigzag layers. When both guests MeOH and MeCN were incorporated into one
      material, [Mn(salen)]2[Mn(N)(CN)4(MeOH)0.25(MeCN)0.75], zero in-plane TE resulted
      in a range of temperature between 380 and 440 K.

PMID- 28492318
TI  - Effect of Deuteration on the Thermodynamic Properties of
      Dioxotetrafluoromolybdate(VI), (NH4)2MoO2F4.
AB  - Thermal and dielectric studies of (ND4)2MoO2F4 crystals undergoing successive
      phase transitions at T1 = 272 K and T2 = 181 K showed that deuteration is
      accompanied by an increase in the chemical pressure in the crystal lattice
      (Deltap ~ 0.02 GPa), which shifts the Cmcm <-> Pnma transformation for the first
      order to the tricritical point. The direct participation of ammonium groups in
      the mechanism of structural distortions is demonstrated by a decrease in the
      entropy of the high-temperature phase transition (DeltaS1 = R ln 6.0). An
      external hydrostatic pressure leads to an expansion of the temperature interval
      of the intermediate antiferroelectric Pnma phase. The triple point on the T-p
      phase diagram, where the Cmcm, Pnma, amd Pnma* phases coexist, can be realized at
      a negative pressure of ptrp ~ -0.8 GPa.

PMID- 28492320
TI  - Hydrazine-Assisted Syntheses and Properties of Mercury Tellurides Containing
      Transition-Metal Complexes.
AB  - With assistance of reactive and coordinative hydrazine, transition-metal
      telluromercurates [Mn(trien)(N2H4)2]2[Hg2Te4]2 (A), [Zn(trien)(N2H4)2]Hg2Te4 (B),
      [Mn(tepa)(N2H4)]2Hg4Te12 (C), [TM(trien)(Hg2Te4)] (TM = Mn (D), Zn (E)), and
      [Zn(atep)]2Hg5Te12 (atep = 4-(2-aminoethyl)triethylenetetramine) (F) were
      solvothermally prepared in triethylenetetramine (trien) or tetraethylenepentamine
      (tepa) solvents using elemental Te as precursor in lower temperature range.
      Compounds A and B consist of mixed coordination cations [TM(trien)(N2H4)2]2+ (TM
      = Mn, Zn) and one-dimensional polyanion [Hg2Te4]2- with the five-membered Hg2Te3
      rings being coplanar. Compound C is composed of two [Mn(tepa)(N2H4)]2+ cations
      and a [Hg4Te12]4- cluster with a centrosymmetric structure. Compounds D and E
      consist of coordination polymer [TM(trien) (Hg2Te4)] containing novel doubled
      [Hg2Te4]n chain with tetrahedrally coordinated Hg(II) centers, which is quite
      different from the common single chain with the same composition of [Hg2Te4]n. D
      and E are the first examples of telluromercurates incorporated with TM complex
      units via TM-Te bonds. Compound F contains fivefold coordinated [Zn(atep)]2+
      cations and zigzag [Hg5Te124-]n polymeric anion. The [Hg5Te124-]n anion is a new
      species of the binary telluromercurates. It is built from [Hg4Te6] and
      [HgTe2(Te4)] subunits via interconnectivity, which generates Hg3Te3 and Hg4Te4
      rings in the structure. Compounds A-F are potential semiconductors with narrow
      band gaps in the range of 0.96-1.09 eV. Photocatalytic investigation of Mn(II)
      complexes show that they are photocatalytically active in the degradation of CV
      under visible-light irradiation with the highest catalytic effective of cluster
      compound C.

PMID- 28492321
TI  - Superionic Behavior and Phase Transition in a Vanthoffite Mineral.
AB  - Crystals of a Vanthoffite mineral, Na6Mn(SO4)4, grown from an aqueous solution,
      belong to a monoclinic system, P21/c, Z = 2, at ambient temperature. Thermal
      analysis indicates a phase transition at 455  degrees C, which was substantiated
      by in situ variable-temperature powder X-ray diffraction. The structure is
      orthorhombic (Pmmm) after the phase transition and reverts to the monoclinic
      system upon cooling. Variable-temperature ionic conductivity measurements show a
      significantly higher value (~10-2 S cm-1) beyond the phase transition
      temperature.

PMID- 28492322
TI  - Hydrogen-Induced Adsorption of Carbon Monoxide on the Gold Dimer Cation: A Joint
      Experimental and DFT Investigation.
AB  - It is demonstrated, using tandem mass spectrometry and radio frequency ion trap,
      that the adsorption of a H atom on the gold dimer cation, Au2H+, prevents its
      dissociation and allows for adsorption of CO. Reaction kinetics are measured by
      employing a radio frequency ion trap, where Au2+ and CO interact for a given
      reaction time. The effect of a hydrogen atom is evaluated by comparing reaction
      rate constants measured for Au2+ and Au2H+. The theoretical results for the
      adsorption of CO molecules and their reaction characteristics with Au2+ and Au2H+
      are found to agree with the experimental findings. The joint investigations
      provide insights into hydrogen atom adsorption effects and consequent reaction
      mechanisms.

PMID- 28492325
TI  - Theoretical Study of the Solvation Effect on the Reductive Reaction of Vinylene
      Carbonate in the Electrolyte Solution of Lithium Ion Batteries.
AB  - Carbon monoxide generation reaction of vinylene carbonate (VC) in the electrolyte
      solution of lithium ion batteries (ethylene carbonate (EC) and 1.0 M LiClO4/EC)
      is studied using the RISM-SCF-SEDD method, a hybrid methodology of statistical
      mechanics for molecular liquids and quantum chemistry. The analytical treatment
      of the solvent and lithium salt enables us to treat the complicated composition
      of the solution such as the concentration of the salt which is difficult for the
      methods based on the molecular dynamics (MD) simulation. The free energy profile
      and solvation structure are discussed in order to clarify the effect of the
      solvent, especially lithium salt on the reaction. The lithium salt strongly
      stabilizes the system due to the electrostatic interaction compared with the
      system in which the salt does not exist. The effect of the salt is especially
      important for considering the ionization process of VC.

PMID- 28492323
TI  - A Mixed-Ring Sandwich Complex from Unexpected Ring Contraction in [Re(eta6
      C6H5Br)(eta6-C6R6)](PF6).
AB  - The contraction of coordinated aromatic hydrocarbons is a rare reactivity pattern
      in organometallic chemistry. We describe the conversion of a bromobenzene
      coordinated to a ReI center into a cyclopentadienyl aldehyde. Under mildly
      alkaline conditions, the expected phenol complex is formed with Re and 99Tc but
      under strong basic conditions; ring contraction occurs in close to quantitative
      yields for Re only. A mechanism for this unprecedented reaction is proposed based
      on 1H and 2H NMR spectra and density functional theory calculations.

PMID- 28492324
TI  - Selective 1H-1H Distance Restraints in Fully Protonated Proteins by Very Fast
      Magic-Angle Spinning Solid-State NMR.
AB  - Very fast magic-angle spinning (MAS > 80 kHz) NMR combined with high-field
      magnets has enabled the acquisition of proton-detected spectra in fully
      protonated solid samples with sufficient resolution and sensitivity. One of the
      primary challenges in structure determination of protein is observing long-range
      1H-1H contacts. Here we use band-selective spin-lock pulses to obtain selective
      1H-1H contacts (e.g., HN-HN) on the order of 5-6 A in fully protonated proteins
      at 111 kHz MAS. This approach is a major advancement in structural
      characterization of proteins given that magnetization can be selectively
      transferred between protons that are 5-6 A apart despite the presence of other
      protons at shorter distance. The observed contacts are similar to those
      previously observed only in perdeuterated proteins with selective protonation.
      Simulations and experiments show the proposed method has performance that is
      superior to that of the currently used methods. The method is demonstrated on GB1
      and a beta-barrel membrane protein, AlkL.

PMID- 28492326
TI  - Pd-Catalyzed Regioselective 1,2-Difunctionalization of Vinylarenes with Alkenyl
      Triflates and Aryl Boronic Acids at Ambient Temperature.
AB  - A Pd-catalyzed highly regioselective 1,2-difunctionalization of vinylarenes is
      disclosed in which multisubstituted olefins are efficiently and conveniently
      constructed under ambient temperature with good compatibility and a broad
      substrate scope. Notably, a quarternary carbon center could be readily built up
      from 1,1-disubstituted styrenes, which are big challenges in the previous
      methods.

PMID- 28492327
TI  - Versatile Methodology for Glycosurfaces: Direct Ligation of Nonderivatized
      Reducing Saccharides to Poly(pentafluorophenyl acrylate) Grafted Surfaces via
      Hydrazide Conjugation.
AB  - In this work, we report a convenient and versatile strategy for surface-grafted
      glycopolymer constructs with the goal of surface modification that controls the
      chemical presentation and grafting density of carbohydrate side chains. This
      approach employs a difunctional hydrazine linker, chemically modified to an
      active ester containing poly(pentafluorophenyl acrylate) grafted scaffold, to
      conjugate a variety of saccharides through the reducing end. The successive
      conjugation steps are carried out under mild conditions and yield high surface
      densities of sugars, as high as 4.8 nmol.cm-2, capable of multivalency, with an
      intact structure and retained bioactivity. We also demonstrate that this
      glycosylated surface can bind specific lectins according to the structure of its
      pendant carbohydrate. To demonstrate bioactivity, this surface platform is used
      to study the binding events of a human respiratory tract pathogen, Mycoplasma
      pneumoniae, on surfaces conjugated with sialylated sugars.

PMID- 28492328
TI  - Inhibition of Radiolytic Molecular Hydrogen Formation by Quenching of Excited
      State Water.
AB  - Comparison of experimental measurements of the yield of molecular hydrogen
      produced in the gamma radiolysis of water and aqueous nitrate solutions with
      predictions of a Monte Carlo track chemistry model shows that the nitrate anion
      scavenging of the hydrated electron, its precursor, and hydrogen atom cannot
      account for the observed decrease in the yield at high nitrate anion
      concentrations. Inclusion of the quenching of excited states of water (formed by
      either direct excitation or reaction of the water radical cation with the
      precursor to the hydrated electron) by the nitrate anion into the reaction scheme
      provides excellent agreement between the stochastic calculations and experiment
      demonstrating the existence of this short-lived species and its importance in
      water radiolysis. Energy transfer from the excited states of water to the nitrate
      anion producing an excited state provides an additional pathway for the
      production of nitrogen containing products not accounted for in traditional
      radiation chemistry scenarios. Such reactions are of central importance in
      predicting the behavior of liquors common in the reprocessing of spent nuclear
      fuel and the storage of highly radioactive liquid waste prior to vitrification.

PMID- 28492329
TI  - Preserved Transmembrane Segment Topology, Structure, and Dynamics in Disparate
      Micellar Environments.
AB  - Detergent micelles are frequently employed as membrane mimetics for solution
      state membrane protein nuclear magnetic resonance spectroscopy. Here we compare
      topology, structure, ps-ns time-scale dynamics, and hydrodynamics of a model
      protein with one transmembrane (TM) segment (residues 1-55 of the apelin
      receptor, APJ, a G-protein-coupled receptor) in three distinct, commonly used
      micellar environments. In each environment, two solvent-protected helical
      segments connected by a solvent-exposed kink were observed. The break in helical
      character at the kink was maintained in a helix-stabilizing fluorinated alcohol
      environment, implying that this structural feature is inherent. Molecular
      dynamics simulations also substantiate favorable self-assembly of compact protein
      micelle complexes with a more dynamic, solvent-exposed kink. Despite the observed
      similarity in TM segment behavior, micelle-dependent differences were clear in
      the structure, dynamics, and compactness of the 30-residue, extramembrane N
      terminal tail of the protein. This would affect intermolecular interactions and,
      correspondingly, the functional state of the membrane protein.

PMID- 28492330
TI  - Synthesis and Properties of Conjugated Macrocycles Containing 2,7-Bis(2-thienyl)
      9H-fluoren-9-one Units.
AB  - Synthetic pathways to conjugated macrocycles containing one, two, or three 2,7
      bis(2-thienyl)-9H-fluoren-9-one (TFOT) units in the macrocyclic frameworks
      bearing 10, 16, or 24 aromatic units were developed. The Diels-Alder reaction
      between (E,E)-1-(5-bromo-2-thienyl)-4-(5-iodo-2-thienyl)-1,3-butadiene and
      dimethyl acetylenedicarboxylate produced the key Diels-Alder adduct for the
      subsequent macrocyclic ring formation. UV-vis and fluorescence spectra of the
      TFOT-containing molecules were recorded, and their electrochemical properties
      were investigated by cyclic and differential pulse voltammetry.
      Solvatofluorochromic properties were observed for the TFOT-containing molecules.

PMID- 28492331
TI  - High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial
      Sulfate Reduction.
AB  - The selective perturbation of complex microbial ecosystems to predictably
      influence outcomes in engineered and industrial environments remains a grand
      challenge for geomicrobiology. In some industrial ecosystems, such as oil
      reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which
      is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis,
      there has been minimal exploration of the chemical space of possible inhibitory
      compounds, and very little work has quantitatively assessed the selectivity of
      putative souring treatments. We have developed a high-throughput screening
      strategy to identify potent and selective inhibitors of SRM, quantitatively
      ranked the selectivity and potency of hundreds of compounds and identified
      previously unrecognized SRM selective inhibitors and synergistic interactions
      between inhibitors. Zinc pyrithione is the most potent inhibitor of
      sulfidogenesis that we identified, and is several orders of magnitude more potent
      than commonly used industrial biocides. Both zinc and copper pyrithione are also
      moderately selective against SRM. The high-throughput (HT) approach we present
      can be readily adapted to target SRM in diverse environments and similar
      strategies could be used to quantify the potency and selectivity of inhibitors of
      a variety of microbial metabolisms. Our findings and approach are relevant to
      efforts to engineer environmental ecosystems and also to understand the role of
      natural gradients in shaping microbial niche space.

PMID- 28492332
TI  - Cellular Fates of Manganese(II) Pentaazamacrocyclic Superoxide Dismutase (SOD)
      Mimetics: Fluorescently Labeled MnSOD Mimetics, X-ray Absorption Spectroscopy,
      and X-ray Fluorescence Microscopy Studies.
AB  - Manganese(II) pentaazamacrocyclic complexes (MnPAMs) can act as small-molecule
      mimics of manganese superoxide dismutase (MnSOD) with potential therapeutic
      application in conditions linked to oxidative stress. Previously, the in vitro
      mechanism of action has been determined, their activity has been demonstrated in
      cells, and some representatives of this class of MnSOD mimetics have entered
      clinical trials. However, MnPAM uptake, distribution, and metabolism in cells are
      largely unknown. Therefore, we have used X-ray fluorescence microscopy (XFM) and
      X-ray absorption spectroscopy (XAS) to study the cellular fate of a number of
      MnPAMs. We have also synthesized and characterized fluorescently labeled (pyrene
      and rhodamine) manganese(II) pyane [manganese(II) trans-2,13-dimethyl-3,6,9,12,18
      pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene] derivatives and investigated
      their utility for cellular imaging of MnPAMs. Their SOD activity was determined
      via a direct stopped-flow technique. XFM experiments show that treatment with
      amine-based manganese(II) pyane type pentaazamacrocycles leads to a 10-100-fold
      increase in the overall cellular manganese levels compared to the physiological
      levels of manganese in control cells. In treated cells in general, manganese was
      distributed throughout the cell body, with a couple of notable exceptions. The
      lipophilicity of the MnPAMs, examined by partitioning in octanol-buffer system,
      was a good predictor of the relative cellular manganese levels. Analysis of the
      XAS data of treated cells revealed that some fraction of amine-based MnPAMs taken
      up by the cells remained intact, with the rest transformed into SOD-active
      manganese(II) phosphate. Higher phosphate binding constants, determined from the
      effect of the phosphate concentration on in vitro SOD activity, were associated
      with more extensive metabolism of the amine-based MnPAMs to manganese(II)
      phosphate. In contrast, the imine-based manganese(II) pydiene complex that is
      prone to hydrolysis was entirely decomposed after uptake and free manganese(II)
      was oxidized to a manganese(III) oxide type species, in cytosolic compartments,
      possibly mitochondria. Complex stability constants (determined for some of the
      MnPAMs) are less indicative of the cellular fate of the complexes than the
      corresponding phosphate binding constants.

PMID- 28492333
TI  - Self-Assembly of Amphiphilic Biotransesterified beta-Cyclodextrins:
      Supramolecular Structure of Nanoparticles and Surface Properties.
AB  - A series of beta-cyclodextrin (betaCD) amphiphilic derivatives with varying
      degrees of substitution were prepared by acylating betaCDs on their secondary
      face using thermolysin to catalyze the transesterification. After dissolution in
      acetone, the betaCD-Cn derivatives (n = 8, 10, 12, 14) were nanoprecipitated in
      water, where they self-organized into structured particles that were
      characterized using cryo-transmission electron microscopy (cryo-TEM) images and
      small-angle X-ray scattering (SAXS) data. Two types of morphologies and
      ultrastructures were observed depending on the total degree of substitution (TDS)
      of the parent derivative. The molecules with TDS < 5 formed nanospheres with a
      multilamellar organization, whereas those with TDS > 5 self-assembled into barrel
      like (n = 8, 10, 12) or more tortuous (n = 14) particles with a columnar inverse
      hexagonal structure. In particular, faceted betaCD-C14 particles (TDS = 7)
      appeared to be composed of several domains with different orientations that were
      separated by sharp interfaces. Ultrastructural models were proposed on the basis
      of cryo-TEM images and the analysis of the contrast distribution in different
      projections of the lattice. Complementary compression isotherm experiments
      carried out at the air-water interface also suggested that differences in the
      molecular conformation of the series of derivatives existed depending on whether
      TDS was lower or higher than 5.

PMID- 28492334
TI  - Solid-Liquid Interface Thermal Resistance Affects the Evaporation Rate of
      Droplets from a Surface: A Study of Perfluorohexane on Chromium Using Molecular
      Dynamics and Continuum Theory.
AB  - We study the role of solid-liquid interface thermal resistance (Kapitza
      resistance) on the evaporation rate of droplets on a heated surface by using a
      multiscale combination of molecular dynamics (MD) simulations and analytical
      continuum theory. We parametrize the nonbonded interaction potential between
      perfluorohexane (C6F14) and a face-centered-cubic solid surface to reproduce the
      experimental wetting behavior of C6F14 on black chromium through the solid-liquid
      work of adhesion (quantity directly related to the wetting angle). The thermal
      conductances between C6F14 and (100) and (111) solid substrates are evaluated by
      a nonequilibrium molecular dynamics approach for a liquid pressure lower than 2
      MPa. Finally, we examine the influence of the Kapitza resistance on evaporation
      of droplets in the vicinity of a three-phase contact line with continuum theory,
      where the thermal resistance of liquid layer is comparable with the Kapitza
      resistance. We determine the thermodynamic conditions under which the Kapitza
      resistance plays an important role in correctly predicting the evaporation heat
      flux.

PMID- 28492335
TI  - Energy-Storage Applications for a pH Gradient between Two Benzimidazole-Ligated
      Ruthenium Complexes That Engage in Proton-Coupled Electron-Transfer Reactions in
      Solution.
AB  - The judicious selection of pairs of benzimidazole-ligated ruthenium complexes
      allowed the construction of a rechargeable proton-coupled electron-transfer
      (PCET)-type redox battery. A series of ruthenium(II) and -(III) complexes were
      synthesized that contain substituted benzimidazoles that engage in PCET
      reactions. The formation of intramolecular Ru-C cyclometalation bonds stabilized
      the resulting ruthenium(III) complexes, in which pKa values of the imino N-H
      protons on the benzimidazoles are usually lower than those for the corresponding
      ruthenium(II) complexes. As a proof-of-concept study for a solution redox battery
      based on such PCET reactions, the charging/discharging cycles of several pairs of
      ruthenium complexes were examined by chronopotentiometry in an H-type device with
      half-cells separated by a Nafion membrane in unbuffered CH3CN/H2O (1/1, v/v)
      containing 0.1 M NaCl. During the charging/discharging cycles, the pH value of
      the solution gradually changed accompanied by a change of the open-circuit
      potential (OCP). The changes for the OCP and pH value of the solution in the
      anodic and cathodic half-cells were in good agreement with the predicted values
      from the Pourbaix diagrams for the pairs of ruthenium complexes used.
      Accordingly, the careful selection of pairs of ruthenium complexes with a
      sufficient potential gradient and a suitably large pKa difference is crucial: the
      charge generated between the two ruthenium complexes changes the OCP and the pH
      difference between the two cells in an unbuffered solution, given that the PCET
      reactions occur at both electrodes and that discharging leads to the original
      state. Because the electric energy is stored as a pH gradient between the half
      cells, new possibilities for PCET-type rocking-chair redox batteries arise.

PMID- 28492336
TI  - Development of indication criteria for preoperative examination in lung cancer.
AB  - Background Systemic examination for distant metastases is generally recommended
      for all lung cancer patients. However, this approach rarely detects distant
      metastases in typically resectable cT1-2N0 non-small-cell lung cancer. The aim of
      this study was to identify factors associated with distant metastases and develop
      indication criteria for preoperative systemic examination in patients with cT1
      2N0 non-small-cell lung cancer, with a particular focus on computed tomography
      imaging of primary lesions. Methods We retrospectively reviewed non-small-cell
      lung cancer patients treated at our institute between 2005 and 2013. Data were
      extracted and compared between two groups: patients diagnosed as cT1-2N0M0 who
      underwent complete resection (M0 group, n = 1530) and those diagnosed as cT1
      2N0M1b who received systemic chemotherapy (M1 group, n = 26). Results The median
      age at diagnosis was significantly lower in the M1 group ( p = 0.015). Although
      carcinoembryonic antigen levels were significantly higher in the M1 group ( p <
      0.001), 42% had normal levels. Tumor diameters in lung and mediastinal windows on
      chest computed tomography were significantly larger, and the proportion
      (mediastinal/lung window tumor diameter ratio) was higher in the M1 group ( p <
      0.001). All 26 patients in the M1 group had a tumor diameter >15 mm and
      mediastinal/lung window ratio >0.75. Conclusions Preoperative systemic
      examination is not necessary in cT1-2N0 non-small-cell lung cancer patients when
      tumor diameters are <=15 mm and mediastinal/lung window ratios are <=0.75.
      According to these criteria, systemic examinations would have been reduced by 40%
      in our cohort.

PMID- 28492337
TI  - Amplatzer vascular plug in occlusion of a pulmonary arteriovenous malformation.
AB  - Pulmonary arteriovenous malformation is a rare condition with abnormal
      communication of the pulmonary artery with the pulmonary vein. It is associated
      with significant morbidity and mortality when patients develop complications.
      Patients with symptomatic pulmonary arteriovenous malformation should be
      considered for intervention. We describe the case of a 54-year-old woman with a
      large right pulmonary arteriovenous malformation who presented with right chest
      pain due to hemothorax. She underwent successful embolotherapy with an Amplatzer
      plug.

PMID- 28492338
TI  - Headache as a presenting symptom of glioma: A cross-sectional study.
AB  - Objective The objective of this study was to analyse the prevalence and the
      clinical features of headache as a presenting symptom of glioma. Methods We
      interviewed 527 consecutive adult patients with histologically confirmed glioma,
      admitted to the Regina Elena National Cancer Institute between 2010 and 2015. We
      defined four headache phenotypes: Tension-type-like headache (TTH), migraine-like
      headache, worsening of a pre-existing headache (WPH) and classic brain tumour
      headache (BTH). Logistic regression analysis was carried out to investigate
      potential risk factors for headache at presentation of glioma. Results 12.5% (n =
      66) of patients with glioma indicated headache as a presenting symptom of their
      disease. Of these, 31 patients (47%) had TTH, while BTH and WPH were reported by
      28 (42%) and seven (11%) patients, respectively. We did not find any case of
      migraine-like headache. Infratentorial ( p = 0.038) and right-sided tumours ( p =
      0.013) were more frequently associated with the presence of headache at onset.
      Patients with TTH were older than patients with BTH and WPH ( p = 0.035). BTH was
      less frequently associated with other neurological signs ( p < 0.0001). The
      multivariate logistic regression analysis showed the localization of the brain
      tumour in the left hemisphere to be a protective factor for the development of
      headache. Conclusions Our study includes a very large series of patients with
      glioma, providing a description of headache phenotype at first presentation of
      disease and investigating possible factors that may influence the clinical
      features of headache.

PMID- 28492339
TI  - Venetoclax for the treatment of patients with chronic lymphocytic leukemia.
AB  - Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the
      intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2
      with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia
      (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to
      tumor lysis syndrome in some patients with a large tumor burden, but this risk
      was subsequently mitigated by a revised study design that included lower initial
      dosing with intrapatient dose ramp up and close tumor lysis syndrome monitoring
      and prophylaxis. Other toxicities, such as neutropenia and gastrointestinal
      adverse events, were manageable. Venetoclax monotherapy resulted in durable and
      deep responses in patients with relapsed, refractory CLL, including for those
      with deletion 17p, leading to the approval of venetoclax by the US FDA for
      relapsed or refractory deletion 17p CLL, and recently to additional approvals in
      Europe and Canada. Trials also suggest that venetoclax induces deeper and more
      durable responses when used in combination with rituximab, and combination
      studies with other agents are ongoing. Phase III trials are also underway, and
      will provide data on the efficacy and safety of venetoclax in combination with
      monoclonal antibodies and targeted therapies in larger patient populations.

PMID- 28492340
TI  - Alterations of zinc homeostasis in response to Cryptococcus neoformans in a
      murine macrophage cell line.
AB  - AIM: To evaluate alterations of zinc homeostasis in macrophages exposed to
      Cryptococcus neoformans. Materials & methods: Using a fluorescent zinc probe
      based flow cytometry and atomic absorption spectrometry, zinc levels were
      evaluated in J774.A1 cell lines exposed to C. neoformans H99 cells. The
      transcription profile of macrophage zinc related homeostasis genes -
      metallothioneins and zinc transporters (ZnTs) of the SLC30 and SLC39 (Zrt-Irt
      protein) families - was analyzed by quantitative PCR. RESULTS: Macrophage
      intracellular labile zinc levels decreased following exposure to C. neoformans. A
      significant decrease in transcription levels was detected in specific ZnTs from
      both the Zrt-Irt-protein and ZnT families, especially 24 h after infection.
      CONCLUSION: These findings suggest that macrophages may exhibit zinc depletion in
      response to C. neoformans infection.

PMID- 28492342
TI  - Social, cognitive, behavioural and neighbourhood characteristics associated with
      sedentary time in men and women living in deprived neighbourhoods.
AB  - Multiple individual and neighbourhood characteristics are theorised to influence
      adult sedentary behaviour. The aim of this study was to examine associations
      between individual and neighbourhood-level characteristics in 40 deprived
      neighbourhoods in London, UK. A cross-sectional design was utilised with baseline
      data from the Well London Cluster Randomised Controlled Trial in 40 deprived
      neighbourhoods in London. Multilevel linear regression was used to examine
      associations between individual characteristics (measured by household survey),
      neighbourhood characteristics (neighbourhood audit, GIS and routinely available
      datasets) and sedentary behaviour (sitting time). Individual-level positive
      mental well-being and health behaviours were associated with sedentary time.
      Individual-level social networks were associated with decreased sedentary time in
      men and increased sedentary time in women. Neighbourhood-level measures of social
      networks and perceived neighbourhood quality were associated with reduced
      sedentary time. Fifteen per cent of the variance in sedentary time was
      attributable to differences at the neighbourhood level (intra-class correlation
      coefficient = 0.15). These findings suggest that social networks at the
      individual and neighbourhood levels, collective perceptions of neighbourhood
      quality, individual-level positive mental well-being and other health behaviours
      may be important components of interventions developed to reduce sedentary time
      in deprived populations.

PMID- 28492341
TI  - Implications of neurovascular uncoupling in functional magnetic resonance imaging
      (fMRI) of brain tumors.
AB  - Functional magnetic resonance imaging (fMRI) serves as a critical tool for
      presurgical mapping of eloquent cortex and changes in neurological function in
      patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent
      (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling
      remains intact during brain tumor progression, and that measured changes in
      cerebral blood flow (CBF) are correlated with neuronal function. Recent
      preclinical and clinical studies have demonstrated that even low-grade brain
      tumors can exhibit neurovascular uncoupling (NVU), which can confound
      interpretation of fMRI data. Therefore, to avoid neurosurgical complications, it
      is crucial to understand the biophysical basis of NVU and its impact on fMRI.
      Here we review the physiology of the neurovascular unit, how it is remodeled, and
      functionally altered by brain cancer cells. We first discuss the latest findings
      about the components of the neurovascular unit. Next, we synthesize results from
      preclinical and clinical studies to illustrate how brain tumor induced NVU
      affects fMRI data interpretation. We examine advances in functional imaging
      methods that permit the clinical evaluation of brain tumors with NVU. Finally, we
      discuss how the suppression of anomalous tumor blood vessel formation with
      antiangiogenic therapies can "normalize" the brain tumor vasculature, and
      potentially restore neurovascular coupling.

PMID- 28492345
TI  - The Focinator v2-0 - Graphical Interface, Four Channels, Colocalization Analysis
      and Cell Phase Identification.
AB  - The quantitative analysis of foci plays an important role in various cell
      biological methods. In the fields of radiation biology and experimental oncology,
      the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on
      DNA damage induction and repair is frequently performed by the analysis of
      protein clusters or phosphorylated proteins recruited to so called repair foci at
      DNA damage sites, involving for example gamma-H2A.X, 53BP1 or RAD51. We recently
      developed "The Focinator" as a reliable and fast tool for automated quantitative
      and qualitative analysis of nuclei and DNA damage foci. The refined software is
      now even more user-friendly due to a graphical interface and further features.
      Thus, we included an R-script-based mode for automated image opening, file
      naming, progress monitoring and an error report. Consequently, the evaluation no
      longer required the attendance of the operator after initial parameter
      definition. Moreover, the Focinator v2-0 is now able to perform multi-channel
      analysis of four channels and evaluation of protein-protein colocalization by
      comparison of up to three foci channels. This enables for example the
      quantification of foci in cells of a specific cell cycle phase.

PMID- 28492343
TI  - Multi-level risk factors associated with sex trading among women living with HIV
      in Kazakhstan: A neglected key population.
AB  - Little is known about the prevalence and risk factors associated with sex trading
      among HIV-positive women. A total of 242 HIV-positive women were recruited in
      five regions in Kazakhstan. These women completed a survey containing items on
      socio-demographics, HIV stigma, intimate partner violence, and partner risk
      behaviors. Multivariate regression was used to examine associations between risk
      factors and sex trading after controlling for socio-demographic factors. Fifty
      six (23.1%) women reported trading sex in the past 90 days. Women who reported
      recent sex trading were more likely than women who did not trade sex in the past
      90 days to experience intimate partner violence (adjusted odds ratio [AOR]: 2.25;
      95% confidence interval [CI]: 1.08-4.73), to have been homeless in the past 90
      days (AOR: 4.12; 95% CI: 1.19-14.29), and to know or suspect a male partner had a
      sexually transmitted infection (AOR: 2.20; 95% CI: 1.07-4.53), had sex with
      another partner (AOR: 4.53; 95% CI: 2.25-9.14), or injected drugs in the past
      year (AOR: 3.31; 95% CI: 1.64-6.65). These findings underscore the need for
      comprehensive HIV prevention and intervention programs that address the multi
      level risk factors associated with sex trading for women infected with HIV.

PMID- 28492346
TI  - Yoga Communities and Eating Disorders: Creating Safe Space for Positive
      Embodiment.
AB  - With adequate education and guidance, yoga communities, as part of the
      therapeutic landscape in the 21st century, can play a significant role promoting
      positive embodiment for those with, and at-risk for, eating disorders (EDs). To
      do this, yoga teachers need to know how to create a body-positive community and
      be able to recognize and respond to those at risk and struggling with EDs in
      their communities. In order to address yoga teaching methods associated with EDs
      and ED risk, broader conceptual approaches and specific practices associated with
      positive embodiment are offered. These include the broader conceptual approaches
      of: intentional inclusion and acceptance, experiential emphasis, supporting
      positive embodiment and inquiry. Studio pragmatics are also detailed as related
      to the body, breath, emotions, and community. Assessment, referral, and community
      engagement are also addressed.

PMID- 28492344
TI  - Andrographis paniculata Diterpenoids Protect against Radiation-Induced
      Transformation in BALB/3T3 Cells.
AB  - One of the most concerning side effects of exposure to radiation are the
      carcinogenic risks. To reduce the negative effects of radiation, both
      cytoprotective and radioprotective agents have been developed. However, little is
      known regarding their potential for suppressing carcinogenesis. Andrographis
      paniculata , a plant, with multiple medicinal uses that is commonly used in
      traditional medicine, has three major constituents known to have cellular
      antioxidant activity: andrographolide (AP1); 14-deoxy-11,12
      didehydroandrographolide (AP3); and neoandrographolide (AP4). In our study, we
      tested these elements for their radioprotective properties as well as their anti
      neoplastic effects on transformation using the BALB/3T3 cell model. All three
      compounds were able to reduce radiation-induced DNA damage. However, AP4 appeared
      to have superior radioprotective properties compared to the other two compounds,
      presumably by protecting mitochondrial function. The compound was able to
      suppress radiation-induced cellular transformation through inhibition of STAT3.
      Treatment with AP4 also reduced expressions of MMP-2 and MMP-9. These results
      suggest that AP4 could be further studied and developed into an anti
      transformation/carcinogenic drug as well as a radioprotective agent.

PMID- 28492347
TI  - The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in
      vitro and in vivo.
AB  - Vglycin, a novel natural polypeptide isolated from pea seeds, possesses
      antidiabetic properties. Our previous studies have shown that Vglycin can induce
      the differentiation of human colon adenocarcinoma cells. We aimed to determine
      the anticancer activity of Vglycin against colon cancer cells and to elucidate
      related apoptosis-inducing mechanisms. Treatment with purified Vglycin
      significantly reduced growth, viability, and colony formation of CT-26, SW480,
      and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating
      the expression of proliferating cell nuclear antigen. Mouse xenograft studies
      showed a 38% inhibition of colon cancer growth in mice treated with Vglycin (20
      mg/kg/day) at day 21. Furthermore, the potential mechanisms involved in Vglycin
      induced cell apoptosis were examined using cell cycle studies, ultrastructural
      examination, as well as apoptosis-associated pathway analysis. The results showed
      that Vglycin significantly promoted apoptosis and G1/S phase cell cycle arrest.
      As revealed by Western blot, the expression of CDK2 and Cyclin D1 was down
      regulated in all three Vglycin-treated colon cancer cells, indicating that the
      CDK2/Cyclin D1 cell cycle pathway involved in the initiation and progression of
      colon cancer. Moreover, the inhibition of Vglycin-induced cell proliferation in
      colon cancer cells was accompanied by alteration of the expression levels of the
      apoptosis-related proteins Bax, Bcl-2 and Mcl-1, and an increase of caspase-3
      activity. Together, our results suggest that Vglycin may be another plant-derived
      peptide that suppresses colon cancer, supporting the continued investigation of
      Vglycin as therapeutic agent for colon cancer. Impact statement The antidiabetic
      properties and the capability of inducing differentiation of human colon
      adenocarcinoma cells of Vglycin have been reported in our previous studies.
      However, the anticancer potential of Vglycin on colon cancer cells and its
      possible related mechanisms were still unknown. In this study, we found that
      Vglycin could reduce growth, viability, and colony formation or colony size of CT
      26, SW480, and NCL-H716 colon cancer cells. Moreover, Vglycin decreased tumor
      volume by 38% in xenograft mice transplanted with CT-26 cells. The mechanisms of
      these phenomena may be due to the down-regulated CDK2 and Cyclin D1, G1/S phase
      cell cycle arrest, and the dysregulated expression of Bax, Bcl-2, and Mcl-1. The
      findings highlight the anticancer potential of Vglycin against colon cancer
      cells, and suggest Vglycin may be another colon cancer potential suppressive
      component of plant-derived peptides.

PMID- 28492348
TI  - Culture of human cells in experimental units for spaceflight impacts on their
      behavior.
AB  - Because space missions produce pathophysiological alterations such as
      cardiovascular disorders and bone demineralization which are very common on
      Earth, biomedical research in space is a frontier that holds important promises
      not only to counterbalance space-associated disorders in astronauts but also to
      ameliorate the health of Earth-bound population. Experiments in space are complex
      to design. Cells must be cultured in closed cell culture systems (from now
      defined experimental units (EUs)), which are biocompatible, functional, safe to
      minimize any potential hazard to the crew, and with a high degree of automation.
      Therefore, to perform experiments in orbit, it is relevant to know how closely
      culture in the EUs reflects cellular behavior under normal growth conditions. We
      compared the performances in these units of three different human cell types,
      which were recently space flown, i.e. bone mesenchymal stem cells, micro- and
      macrovascular endothelial cells. Endothelial cells are only slightly and
      transiently affected by culture in the EUs, whereas these devices accelerate
      mesenchymal stem cell reprogramming toward osteogenic differentiation, in part by
      increasing the amounts of reactive oxygen species. We conclude that cell culture
      conditions in the EUs do not exactly mimic what happens in a culture dish and
      that more efforts are necessary to optimize these devices for biomedical
      experiments in space. Impact statement Cell cultures represent valuable
      preclinical models to decipher pathogenic circuitries. This is true also for
      biomedical research in space. A lot has been learnt about cell adaptation and
      reaction from the experiments performed on many different cell types flown to
      space. Obviously, cell culture in space has to meet specific requirements for the
      safety of the crew and to comply with the unique environmental challenges. For
      these reasons, specific devices for cell culture in space have been developed. It
      is important to clarify whether these alternative culture systems impact on cell
      performances to allow a correct interpretation of the data.

PMID- 28492350
TI  - The underestimated role of somatostatin analogs in the NETTER-1 trial.

PMID- 28492349
TI  - A novel compressive stress-based osteoarthritis-like chondrocyte system.
AB  - Mechanical stress damage and insufficient self-repair can contribute to
      osteoarthritis (OA) in the affected joint. As the effects of stress on
      chondrocyte metabolism can regulate cartilage homeostasis, the specific stress
      response condition is therefore a key to the generation of an OA disease model.
      We aimed to produce a specific stress- and cell-based OA model after evaluating
      the metabolic responses of chondrocytes in response to a series of static and
      cyclic compression stressors. A static load exceeding 40 psi initiated
      extracellular matrix (ECM) degradation through a decrease in the sulphated
      glycosaminoglycan (GAG) content, upregulation of catabolic matrix
      metalloproteinase (MMP)-13 encoding gene expression, and downregulation of the
      ECM-related aggrecan and type II collagen encoding genes within 24 h. Indicators
      of pro-inflammatory events and oxidative stress were found to correlate with
      increased IL-6 expression and reactive oxygen species (ROS) production,
      respectively. However, chondrocytes stimulated by moderate cyclic loading (30-40
      psi) exhibited increased ECM-related gene expression without significant changes
      in catabolic and pro-inflammatory gene expression. BMP-7 expression increased at
      cyclic loading levels above 30-60 psi. These results demonstrated that static
      compression exceeding 60 psi is sufficient to produce OA-like chondrocytes that
      exhibit signs of ECM degradation and inflammation. These OA-like chondrocytes
      could therefore be used as a novel cell-based drug screening system. Impact
      statement The lack of an effective treatment for osteoarthritis (OA) reflects the
      great need for alternative therapies and drug discovery. Disease models can be
      used for early-stage compound screening and disease studies. Chondrocytes are
      solely responsible for the maintenance of the articular cartilage extracellular
      matrix. Our strategy involved the generation of a cell-based model of OA, a more
      readily studied disease. Instead of using animal cartilage explants, we
      incorporated isolated porcine chondrocytes with hydrogel to form three
      dimensional assemblies. We could identify the specific magnitude-dependent
      metabolic responses of chondrocytes by applying a series of static and cyclic
      compression, and therefore successfully generated a novel OA-like cell-based
      model for drug screening.

PMID- 28492351
TI  - mesT, a unique epoxide hydrolase, is essential for optimal growth of
      Mycobacterium tuberculosis in the presence of styrene oxide.
AB  - AIM: mesT of Mycobacterium tuberculosis, a hypothetical/putative epoxide
      hydrolase, is predicted to convert toxic epoxides to the more water-soluble and
      less toxic diols. Detailed characterization of the protein was carried out.
      RESULTS: mesT demonstrated esterase as well as epoxide hydrolase activity. It was
      membrane bound and was upregulated under hypoxic conditions. The enzyme was able
      to degrade styrene oxide. The presence of antisense against this gene resulted in
      the inhibition of in vitro bacterial growth/survival in the presence of styrene
      oxide. Conclusion & future perspective: We demonstrated that mesT possessed
      epoxide hydrolase activity and styrene oxide might be its physiological
      substrate. Inhibition of mesT reduced the growth of the bacteria in presence of
      styrene oxide and its expression under hypoxic condition suggested its role in
      intracellular survival of bacteria.

PMID- 28492352
TI  - The Physiological Incubation Biosimulator (PIBS): An Improved Ex Vivo
      Experimental Setup for the Mechanical Stability of Biological Sealants in
      Surgical Procedures.
AB  - BACKGROUND: Tissue-bound fibrin sealants are used in a wide array of surgical
      procedures. The microenvironmental interaction between sealant and application
      site is often poorly evaluated due to a lack of suitable experimental models.
      METHODS: A physiological incubation biosimulator (PIBS) was developed to test
      biological sealants in an ex vivo setup under physiological conditions comparable
      to the microenvironment at application site (temperature, humidity, pressure).
      PIBS was validated by a study on the effectiveness of TachoSil for leak closure
      at pancreatic resection sites. Defined defects in a thoracic membrane of porcine
      origin were sealed by TachoSil. Integrity of the sealing was tested in the
      presence of active pancreatic fluid over 60 minutes. Heat-inactivated pancreatic
      fluid and electrolyte solution served as controls. The time to leakage was
      recorded and experimental groups were analyzed by Kaplan-Meier analysis. RESULTS:
      PIBS produced reliable results. TachoSil lead to a leakage rate of 96% after
      incubation with active pancreatic fluid (p = 34), which was significantly higher
      compared with heat-inactivated pancreatic fluid (p = 34, 52%) or electrolyte
      solution (p = 20, 19%). CONCLUSION: PIBS is an effective tool to evaluate
      microenvironmental effects on the adhesive strength of biomaterials. Tissue
      sealing effect of TachoSil is diminished in a "pancreatic" microenvironment rich
      with pancreatic enzymes. Our results might therefore explain the reason of the
      findings of randomized controlled trials recently published on this subject.

PMID- 28492353
TI  - Laparoscopy Using Room Air Insufflation in a Rural African Jungle Hospital: The
      Bongolo Hospital Experience, January 2006 to December 2013.
AB  - INTRODUCTION: Carbon dioxide is the standard insufflation gas for laparoscopy.
      However, in many areas of the world, bottled carbon dioxide is not available.
      Laparoscopy offers advantages over open surgery and has been practiced using
      filtered room air insufflation since 2006 at Bongolo Hospital in Gabon, Africa.
      OBJECTIVE: Our primary goal was to evaluate the safety of room air insufflation
      related to intraoperative and postoperative complications. Our secondary aim was
      to review the types of cases performed laparoscopically at our institution.
      METHODS: This retrospective review evaluates laparoscopic cases performed at
      Bongolo Hospital between January 2006 and December 2013. Demographic and
      perioperative information for patients undergoing laparoscopic procedures was
      collected. Insufflation was achieved using a standard, oil-free air compressor
      using filtered air and a standard insufflation regulator. RESULTS: A total of 368
      laparoscopic procedures were identified within the time period. The majority of
      cases were gynecologic (43%). There was a 2% (8/368) complication rate with one
      perioperative death. The 2 complications related to insufflation were episodes of
      hypotension responsive to standard corrective measures. No intracorporeal
      combustion events were observed in any cases in which the use of diathermy and
      room air insufflation were combined. The other complications and the death were
      unrelated to the use of insufflation with air. CONCLUSION: Insufflation
      complications with room air occurred in our study. However, the complications
      related to insufflation with room air in our study were no different than those
      described in the literature using carbon dioxide. As room air is less costly than
      carbon dioxide and readily available, confirming the safety of room air
      insufflation in prospective studies is warranted. Room air appears to be safe for
      establishing and maintaining pneumoperitoneum, making laparoscopic surgery more
      accessible to patients in low-resource settings.

PMID- 28492354
TI  - Experimental Evaluation of the Optimal Suture Pattern With a Flexible Endoscopic
      Suturing System.
AB  - BACKGROUND: The ability to perform reliable, secure endoluminal closure of the
      gastrointestinal tract wall, is a prerequisite to support the progress of the
      emerging field of endoluminal surgery. Along with advanced clipping systems,
      flexible endoscopic suturing devices are commercially available. Current systems
      can replicate traditional surgical suturing patterns in the endoluminal
      environment. The aim of this study was to evaluate the optimal endoluminal
      suturing technique using a flexible endoscopic suturing device. MATERIALS AND
      METHODS: Procedures were performed on bench-top simulators containing 20
      explanted porcine stomachs. A standardized 3-cm full-thickness incision was
      created on the anterior wall of each stomach using monopolar cautery. The
      gastrotomy was closed endoscopically using an over-the-scope suturing device
      (OverStitch, Apollo Endosurgery; Austin, TX). Three different techniques were
      used: single stitches, figure-of-8 pattern, and running suture. Material
      consumption and operation time were recorded and bursting pressure measurement of
      the closure was performed. RESULTS: No statistically significant differences were
      identified in suturing time. Suturing time (minutes) was slightly shorter with
      the figure-of-8 technique (41.14 +/- 4.6) versus interrupted (45.75 +/- 1.1)
      versus continuous (51.44 +/- 10.0), but the difference was not statistically
      significant. The number of sutures required was greater in the interrupted group.
      No significant difference was found in the burst pressure (mm Hg): figure-of-8
      (45.85 +/- 26.2) versus interrupted (30.5 +/- 22.89) versus continuous (32.0 +/-
      26.5). In the figure-of-8 group, 85.5% of cases were leakproof above 30 mm Hg,
      while in the other groups only 50% of cases were so. CONCLUSION: A figure-of-8
      suturing pattern seems to be the preferable suturing technique with the
      endoscopic suturing device.

PMID- 28492355
TI  - Experimental Procedure of Compression Anastomosis Using Fragmented Rings: A
      Porcine Model.
AB  - BACKGROUND: Compression anastomosis has been recently abandoned because of a
      nonsuperiority compared to stapling anastomosis. Nonremoval of the rings has
      frequently been reported and this technique does not support a routine use. The
      aim of this experimental study was to assess the feasibility of anastomosis using
      compression with a device consisting of fragmented rings. METHODS: A new
      compression device, the "Anastocom," was compared to standard double-stapled
      colocolonic anastomosis in 2 groups of 8 pigs. In each group, colocolonic
      anastomosis was performed with a circular stapler (DST Series EEA Staplers) in 4
      pigs and with the Anastocom device for the other 4 pigs. RESULTS: The anastomotic
      rings were expelled between postoperative day 7 and day 13 from the 4 animals
      sacrificed at day 30. The anastomosis was clean and intact in all pigs. After
      sacrifice, there was no difference in the bursting pressure at day 7 ( P = .226)
      or at day 30 ( P = .885) between the 2 types of anastomosis. After sacrifice at
      day 7, the mean bursting pressure values for the Anastocom and EEA anastomoses
      were 128.6 mm Hg (range 119-143 mm Hg) and 218.9 mm Hg (range 84-240 mm Hg),
      respectively. After sacrifice at day 30, the mean bursting pressure values for
      the Anastocom and EEA anastomoses were 111 mm Hg (range 59-234 mm Hg) and 105 mm
      Hg (range 81-130 mmHg), respectively. CONCLUSION: No bowel obstruction was
      observed with Anastocom. This fragmentation mechanism should better prevent
      nonexpulsion compared to basic compression anastomosis.

PMID- 28492356
TI  - High-Frequency Irreversible Electroporation: Safety and Efficacy of Next
      Generation Irreversible Electroporation Adjacent to Critical Hepatic Structures.
AB  - Irreversible electroporation (IRE) is a nonthermal ablation modality employed to
      induce in situ tissue-cell death. This study sought to evaluate the efficacy of a
      novel high-frequency IRE (H-FIRE) system to perform hepatic ablations across, or
      adjacent to, critical vascular and biliary structures. Using ultrasound guidance
      H-FIRE electrodes were placed across, or adjacent to, portal pedicels, hepatic
      veins, or the gall bladder in a porcine model. H-FIRE pulses were delivered (2250
      V, 2-5-2 pulse configuration) in the absence of cardiac synchronization or
      intraoperative paralytics. Six hours after H-FIRE the liver was resected and
      analyzed. Nine ablations were performed in 3 separate experimental groups (major
      vessels straddled by electrodes, electrodes placed adjacent to major vessels,
      electrodes placed adjacent to gall bladder). Average ablation time was 290 +/- 63
      seconds. No electrocardiogram abnormalities or changes in vital signs were
      observed during H-FIRE. At necropsy, no vascular damage, coagulated-thermally
      desiccated blood vessels, or perforated biliary structures were noted.
      Histologically, H-FIRE demonstrated effective tissue ablation and uniform
      induction of apoptotic cell death in the parenchyma independent of vascular or
      biliary structure location. Detailed microscopic analysis revealed minor
      endothelial damage within areas subjected to H-FIRE, particularly in regions
      proximal to electrode insertion. These data indicate H-FIRE is a novel means to
      perform rapid, reproducible IRE in liver tissue while preserving gross
      vascular/biliary architecture. These characteristics raise the potential for long
      term survival studies to test the viability of this technology toward clinical
      use to target tumors not amenable to thermal ablation or resection.

PMID- 28492357
TI  - Long-Term Effectiveness of Strattice in the Laparoscopic Closure of
      Paraesophageal Hernias.
AB  - Prosthetic reinforcement reduces the recurrence rate of large paraesophageal
      hernias (PEH), but the use of synthetic or biosynthetic mesh in the repair
      remains controversial. PEH repair has reported recurrence rates of 12% to 42%,
      and primary repair of PEH by suture closure under tension is at high risk of
      disruption. Synthetic mesh use in large PEH repair has shown to reduce recurrence
      but can lead to problems including mesh erosion, ulceration, stricture, and
      dysphagia. The objective of this study was to examine the long-term safety and
      efficacy of Strattice biologic mesh, a porcine acellular dermal matrix, in crural
      reinforcement of laparoscopic large PEH repair. Thirty-five patients with
      symptomatic PEH (>5 cm) were consented to receive Strattice for PEH repair.
      Patients were seen in clinic preoperatively, at surgery, and 2 weeks, 6 months,
      and 12 months postoperatively. Patients were given a standard subjective reflux
      test at each visit and a 12-month barium swallow X-ray to test for recurrence.
      Hernia recurrence was documented in 14.3% of cases by the end of the 1-year
      follow-up. Symptoms improved in 75% to 100% of patients by 6 months, and 33% to
      100% of patients were still reporting symptom improvement at 12 months. Strattice
      mesh in PEH repair results in similar outcomes to other absorbable meshes, and
      the recurrence rate is within the 12% to 42% range of recurrences reported in
      studies outside of our institution. The use of Strattice mesh in large PEH repair
      had results similar to other biomaterial meshes and successfully decreased
      patients' symptom scores through surgical intervention.

PMID- 28492358
TI  - Absorbable Meshes in Inguinal Hernia Surgery: A Systematic Review and Meta
      Analysis.
AB  - PURPOSE: Absorbable meshes used in inguinal hernia repair are believed to result
      in less chronic pain than permanent meshes, but concerns remain whether
      absorbable meshes result in an increased risk of recurrence. The aim of this
      study was to present an overview of the advantages and limitations of fully
      absorbable meshes for the repair of inguinal hernias, focusing mainly on
      postoperative pain and recurrence. METHODS: This systematic review with meta
      analyses is based on searches in PubMed, Embase, Cochrane, and Psychinfo.
      Included study designs were case series, cohort studies, randomized controlled
      trials (RCTs), and non-RCTs. Studies had to include adult patients undergoing an
      inguinal hernia repair with a fully absorbable mesh. RESULTS: The meta-analyses
      showed no difference in recurrence rates (median 18 months follow-up) and chronic
      pain rates (1 year follow-up) between absorbable- and permanent meshes. Crude
      chronic pain rates for the RCTs were 2.1% for the absorbable meshes and 7.6% for
      the permanent meshes. For the absorbable meshes, medial hernias were more
      susceptible for recurrence compared with lateral hernias ( P < .0005). None of
      the studies reported allergic reactions or other serious adverse events related
      to the absorbable mesh. CONCLUSIONS: Patients with an absorbable mesh seem to
      have less chronic pain following inguinal hernia surgery compared with permanent
      meshes, without increased risk of recurrence.

PMID- 28492359
TI  - Periodontitis and Endothelial Dysfunction: Periodontal Clinical Parameters and
      Levels of Salivary Markers Interleukin-1beta, Tumor Necrosis Factor-alpha, Matrix
      Metalloproteinase-2, Tissue Inhibitor of Metalloproteinases-2 Complex, and Nitric
      Oxide.
AB  - BACKGROUND: Periodontitis has been associated with a greater risk for
      atherosclerotic cardiovascular disease (ACD). Endothelial dysfunction (ED) is a
      parameter of early ACD, and its association with periodontitis has rarely been
      investigated to date. The objective of this study is to evaluate the association
      between periodontitis and ED by means of periodontal clinical parameters and
      salivary markers interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha,
      nitric oxide (NO), and matrix metalloproteinase (MMP)-2 and tissue inhibitor of
      metalloproteinases (TIMP)-2 complex. METHODS: Forty-seven individuals were
      divided into two groups: 1) 24 individuals with chronic periodontitis (CP); and
      2) 23 individuals without CP. Periodontal examinations of bleeding on probing
      (BOP), probing depth (PD), and clinical attachment level (CAL) were performed. ED
      was evaluated by means of flow-mediated dilatation (FMD) of the brachial artery.
      Salivary concentrations of IL-1beta, TNF-alpha, and MMP-2/TIMP-2 complex were
      assessed using enzyme-linked immunosorbent assay. NO determination was based on
      the reaction of Griess. RESULTS: Individuals with CP presented higher occurrence
      of ED than individuals without CP (P = 0.03 after reactive hyperemia; P = 0.05
      after sublingual nitrate). A significant association among the production of MMP
      2/TIMP-2 complex with the presence of CP (P = 0.008) and periodontal parameters
      PD, CAL, and BOP was identified. Concentration of salivary markers IL-1beta, TNF
      alpha, and NO was similar in individuals with and without CP. A significant
      positive correlation between NO and ED was also identified. CONCLUSIONS:
      Periodontitis was positively associated with ED, expressed by a smaller
      percentage of FMD of the brachial artery and higher salivary levels of MMP-2/TIMP
      2 complex. Additionally, salivary levels of NO were significantly associated with
      better functioning of the vascular endothelium.

PMID- 28492360
TI  - Resveratrol Inhibits Periodontitis-Related Bone Loss in Rats Subjected to
      Cigarette Smoke Inhalation.
AB  - BACKGROUND: Alternative therapeutic approaches have been explored to modulate
      host response to periodontal disease. Knowledge of new strategies to treat
      periodontitis is particularly relevant in patients presenting augmented risk to
      periodontitis, such as smokers. The aim of this study is to investigate the
      impact of resveratrol (RESV) on progression of experimental periodontitis (EP) in
      the presence of cigarette smoke inhalation (CSI). METHODS: Rats were assigned to
      one of three groups: 1) CSI+RESV (n = 20); 2) CSI+placebo (n = 20); and 3) non
      CSI (n = 20). CSI was initiated 1 week prior to initiation of RESV or placebo
      administration (systemically for 30 days) and was continued until the end of the
      study. EP was induced around the first mandibular and second maxillary molars
      using ligatures. Specimens from the mandible were processed for morphometric and
      microcomputed tomography examination of bone volume/levels. Gingival tissues
      surrounding mandibular molars were collected for quantification of interleukin
      (IL)-1beta, IL-4, IL-6, IL-17, and tumor necrosis factor-alpha using an assay
      system. Additional analyses of immunoinflammatory mediator performance (T-helper
      Type 17 [Th17]/Th2 and Th1/Th2 cell levels) were performed according to Th cell
      responses in gingival tissues. Gingival tissues of maxillary molars were
      subjected to real-time polymerase chain reaction for assessment of
      osteoprotegrin, runt-related transcription factor-2, receptor activator of
      nuclear factor-kappa B ligand (RANKL), sclerostin, and Dickkopf Wnt signaling
      pathway inhibitor 1 levels. RESULTS: Higher linear alveolar bone loss (ABL) and
      lower interradicular bone density were detected in ligated molars in the
      CSI+placebo group (P <0.05). IL-4 level was the highest, and Th17/Th2 levels were
      the lowest in RESV-treated rats compared with placebo rats (P <0.05). RESV
      reduced expression of messenger RNA for RANKL in animals receiving CSI (P <0.05).
      CONCLUSION: RESV inhibits EP and CSI-induced supporting ABL and has a beneficial
      effect on osteo-immunoinflammatory markers.

PMID- 28492361
TI  - Influence of rs2228570 on Transcriptional Activation by the Vitamin D Receptor in
      Human Gingival Fibroblasts and Periodontal Ligament Cells.
AB  - BACKGROUND: rs2228570 is the only known single nucleotide polymorphism of the
      vitamin D receptor (VDR) that alters the protein structure. VDRs can be
      distinguished using the restriction endonuclease FokI and accordingly divided
      into three genotypes: FF, Ff, and ff. Influence of rs2228570 on transcriptional
      activation by VDRs in human gingival fibroblasts (hGFs) and periodontal ligament
      cells (hPDLCs) is investigated in this study. METHODS: From 15 donors, hGFs and
      hPDLCs were cultured, genomic DNA was extracted, and genotypes were determined
      using the polymerase chain reaction (PCR)-restriction fragment length
      polymorphism method. Cells were stimulated with calcitriol with or without VDR
      antagonist ZK159222 or osteogenic induction. Alkaline phosphatase, osteocalcin,
      and VDR messenger RNA (mRNA) expression were detected using real-time PCR.
      Alkaline phosphatase and osteocalcin protein expression were detected by enzyme
      activity assays with p-nitrophenyl phosphate substrate and enzyme-linked
      immunosorbent assay, respectively. RESULTS: Among the 15 donor cell cultures, the
      number of FF, ff, and Ff genotypes were 5, 3, and 7, respectively. There were no
      significant differences in expression of alkaline phosphatase or osteocalcin
      among the three genotypes in hGFs. However, after stimulation with calcitriol,
      alkaline phosphatase and osteocalcin mRNA levels in FF-hPDLCs were significantly
      higher than in other hPDLCs genotypes, as was osteocalcin protein expression.
      Furthermore, when ZK159222 was included, this difference disappeared, and when
      osteogenic induction was performed, alkaline phosphatase and osteocalcin mRNA and
      protein levels were higher in FF-hPDLCs than in the other hPDLCs genotypes.
      CONCLUSION: The FF-VDR genotype is associated with the most remarkable
      upregulation of alkaline phosphatase and osteocalcin in hPDLCs.

PMID- 28492362
TI  - Microbiota Analysis of Biofilms on Experimental Abutments Mimicking Dental
      Implants: An In Vivo Model.
AB  - BACKGROUND: The microbiota colonizing dental implants has been said to be similar
      to the microbiome surrounding teeth. In the absence of inflammation, a biofilm
      with pathologic bacteria can cover implant surfaces exposed to the oral cavity,
      for example, due to a remodeling process. The aim of the present study is to
      identify microbiota surrounding exposed dental implants in patients with and
      without a history of periodontitis through a deep-sequencing approach. METHODS:
      An experimental abutment with the same surface and structure as a commercially
      available dental implant was used. Bacterial DNA was isolated, and the 16S
      ribosomal RNA gene was amplified and sequenced. Multiplexed tag-encoded
      sequencing of DNA from the samples was performed, and the reads were processed by
      metagenomic rapid annotation. RESULTS: A wide variety of bacteria, 96 species,
      were identified. The most frequently found bacteria were Fusobacterium nucleatum
      and Prevotella denticola. Some species generally associated with periodontitis
      were found to a greater extent in patients without a history of periodontitis.
      Some bacteria that have never been described as part of the oral microbiome were
      identified in the present sample. CONCLUSIONS: Analysis of data suggests that the
      bacteria surrounding exposed dental implants form a diverse microbiome regardless
      of the periodontal profile of patients. Further research is needed to clarify the
      role of these microorganisms in the oral environment.

PMID- 28492363
TI  - Vagus nerve stimulation improves working memory performance.
AB  - Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major
      depression. While the impact of this treatment on seizures has been established,
      its impact on human cognition remains equivocal. The goal of this study is to
      elucidate the immediate effects of vagus nerve stimulation on attention,
      cognition, and emotional reactivity in patients with epilepsy. Twenty patients
      (12 male and 8 female; 45 +/- 13 years old) treated with VNS due to refractory
      epilepsy participated in the study. Subjects performed a computer-based test of
      executive functions embedded with emotional distractors while their brain
      activity was recorded with electroencephalography. Subjects' cognitive
      performance, early visual event-related potential N1, and frontal alpha asymmetry
      were studied when cyclic vagus nerve stimulation was on and when it was off. We
      found that vagus nerve stimulation improved working memory performance as seen in
      reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63
      (95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) =
      10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction
      time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) =
      11.79, p = .003, in response to threat-related distractors. This is the first
      study to show immediate improvement in working memory performance in humans with
      clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation
      had immediate effects on emotional reactivity evidenced in behavior and brain
      physiology.

PMID- 28492364
TI  - Na+ influx via Orai1 inhibits intracellular ATP-induced mTORC2 signaling to
      disrupt CD4 T cell gene expression and differentiation.
AB  - T cell effector functions require sustained calcium influx. However, the
      signaling and phenotypic consequences of non-specific sodium permeation via
      calcium channels remain unknown. alpha-SNAP is a crucial component of Orai1
      channels, and its depletion disrupts the functional assembly of Orai1 multimers.
      Here we show that alpha-SNAP hypomorph, hydrocephalus with hopping gait,
      Napahyh/hyh mice harbor significant defects in CD4 T cell gene expression and
      Foxp3 regulatory T cell (Treg) differentiation. Mechanistically, TCR stimulation
      induced rapid sodium influx in Napahyh/hyh CD4 T cells, which reduced
      intracellular ATP, [ATP]i. Depletion of [ATP]i inhibited mTORC2 dependent
      NFkappaB activation in Napahyh/hyh cells but ablation of Orai1 restored it.
      Remarkably, TCR stimulation in the presence of monensin phenocopied the defects
      in Napahyh/hyh signaling and Treg differentiation, but not IL-2 expression. Thus,
      non-specific sodium influx via bonafide calcium channels disrupts unexpected
      signaling nodes and may provide mechanistic insights into some divergent
      phenotypes associated with Orai1 function.

PMID- 28492365
TI  - The Hippo pathway effector YAP is an essential regulator of ductal progenitor
      patterning in the mouse submandibular gland.
AB  - Salivary glands, such as submandibular glands (SMGs), are composed of branched
      epithelial ductal networks that terminate in acini that together produce,
      transport and secrete saliva. Here, we show that the transcriptional regulator
      Yap, a key effector of the Hippo pathway, is required for the proper patterning
      and morphogenesis of SMG epithelium. Epithelial deletion of Yap in developing
      SMGs results in the loss of ductal structures, arising from reduced expression of
      the EGF family member Epiregulin, which we show is required for the expansion of
      Krt5/Krt14-positive ductal progenitors. We further show that epithelial deletion
      of the Lats1 and Lats2 genes, which encode kinases that restrict nuclear Yap
      localization, results in morphogenesis defects accompanied by an expansion of
      Krt5/Krt14-positive cells. Collectively, our data indicate that Yap-induced
      Epiregulin signaling promotes the identity of SMG ductal progenitors and that
      removal of nuclear Yap by Lats1/2-mediated signaling is critical for proper
      ductal maturation.

PMID- 28492367
TI  - Correction: Functional double dissociation within the entorhinal cortex for
      visual scene-dependent choice behavior.

PMID- 28492369
TI  - C-Reactive Protein Levels Together with the Ranson Scoring System to
      Differentiate the Mild and Severe Forms of Acute Pancreatitis.

PMID- 28492366
TI  - Digitizing mass spectrometry data to explore the chemical diversity and
      distribution of marine cyanobacteria and algae.
AB  - Natural product screening programs have uncovered molecules from diverse natural
      sources with various biological activities and unique structures. However, much
      is yet underexplored and additional information is hidden in these exceptional
      collections. We applied untargeted mass spectrometry approaches to capture the
      chemical space and dispersal patterns of metabolites from an in-house library of
      marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics
      signals detected were not found in other available datasets of similar nature,
      supporting the hypothesis that marine cyanobacteria and algae possess distinctive
      metabolomes. The data were plotted onto a world map representing eight major
      sampling sites, and revealed potential geographic locations with high chemical
      diversity. We demonstrate the use of these inventories as a tool to explore the
      diversity and distribution of natural products. Finally, we utilized this tool to
      guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine
      cyanobacterium.

PMID- 28492370
TI  - Non-invasive diagnosis of esophageal varices after Baveno VI.
AB  - A major complication of portal hypertension in patients with cirrhosis is the
      development of esophageal varices with the associated risk of variceal bleeding.
      Hence, the Baveno consensus on portal hypertension in its first five editions had
      recommended surveillance with periodic upper endoscopies in these patients to
      identify in a timely fashion the development of esophageal varices and initiate a
      primary prophylaxis strategy in those at a high risk of bleeding. For the first
      time, the Sixth Baveno Consensus on Portal Hypertension (Baveno VI) recommended
      using non-invasive tools to rule out the presence of varices with a high risk of
      bleeding. According to Baveno VI, surveillance endoscopy is not necessary for
      patients with "compensated advanced chronic liver disease" (cACLD) who have
      normal platelets (>150*109/L) and a liver stiffness measure (LSM) <20 kPa. In
      this review, we will briefly describe the currently available non-invasive
      methods to predict the presence of varices, such as serum tests, imaging, and
      elastography. We will also discuss the rationale that led to Baveno VI
      recommendation and describe the studies that have validated Baveno VI criteria
      after its publication. Finally, we will mention some potential caveats and
      suggest some areas for future research.

PMID- 28492371
TI  - Prognostic value of tumoral expression of galectin-9 in gastric cancer.
AB  - BACKGROUND/AIMS: Galectin-9 (Gal-9) is a member of the beta-galactoside-binding
      lectin family. Our previous study revealed that Gal-9 suppresses migration,
      invasion, and epithelial-mesenchymal transition in gastric cancer cells. Gal-9
      was reported to have anti-metastatic activity in patients with malignant
      melanoma, breast cancer, and hepatocellular carcinoma. Therefore, we aimed to
      evaluate the prognostic significance of Gal-9 in patients with gastric cancer.
      MATERIALS AND METHODS: The clinical significance of Gal-9 was explored using
      clinical and pathological data from 619 patients with gastric cancer who
      underwent gastrectomy at National Cancer Center, Korea. Tissue microarray and
      immunohistochemical analyses were used to evaluate Gal-9 expression. The median
      follow-up duration was 65.7 months (range 0-79 months). Kaplan-Meier method was
      used to evaluate survival. Log-rank test was used to assess the differences in
      survival. RESULTS: Based on the tumoral expression of Gal-9, 619 patients with
      gastric cancer were classified into two groups: Gal-9-positive patients (327,
      52.8%) and Gal-9-negative patients (292, 47.2%). The Gal-9-positive group had a
      significantly lower overall (p=0.001, by log-rank test) and gastric cancer
      specific mortalities (p<0.001) compared to the Gal-9-negative group. In
      multivariate analysis, which included the depth of invasion and lymph-node
      metastasis, Gal-9 positivity showed a trend toward improved prognosis but did not
      reach statistical significance (hazard ratio, 0.8; 95% confidence interval, 0.55
      1.31). CONCLUSION: Tumoral expression of Gal-9 may suppress tumor progression in
      patients with gastric cancer.

PMID- 28492372
TI  - Re: HLA is better than serological screening for celiac diseases in
      rheumatological arthritis.

PMID- 28492373
TI  - Re: How to predict the severity of acute pancreatitis? An ongoing debate.

PMID- 28492374
TI  - A miniaturized wall-climbing segment robot inspired by caterpillar locomotion.
AB  - Caterpillars are very successful soft-bodied climbers that navigate in complex
      environments. This paper develops a multi-segmented robot climbing on vertical
      surfaces using dry adhesive pads, inspired by caterpillar locomotion. The
      miniaturized robot consists of four segments, and each segment uses a solenoid
      actuator with a permanent magnet plunger. The head and body segments adapt a
      novel mechanism and Scott-Russell linkages to generate a bi-directional plane
      motion using one solenoid actuator, resulting to reliable attaching and peeling
      motions of gecko pads. A tail is also attached at the back of the last segment to
      avoid falling or exhibiting unstable motion. Gecko-inspired adhesive pads are
      fabricated from polydimethylsiloxane (PDMS) with the area of 20 mm  *  10 mm. We
      have conducted experiments on the locomotion performance of the segment robot
      climbing vertical surfaces for two types of locomotion, achieving the fast and
      stable climbing motion.

PMID- 28492375
TI  - Combat Experience and Mental Health in the Israel National Health Survey.
AB  - OBJECTIVE: To compare the mental health status of those who participated in
      combat related activities during their service with that of soldiers whose army
      service did not include combat related activities Method: A representative sample
      extracted from the National Population Register of non-institutionalized
      residents aged 21 or older of Israel was used in this crosssectional survey. Data
      on mental health disorders, sociodemographic background and army service were
      collected using face-to-face computer-assisted interviews. RESULTS: Combat
      experience per se was not associated with lifetime diagnosis of PTSD. Former
      combat soldiers had significantly lower lifetime prevalence and 12 months
      prevalence of any mood or anxiety disorders including PTSD. CONCLUSION: This work
      is in line with previous literature showing that combat exposure, as such, has
      limited contribution to lifetime PTSD in some groups of veterans. The inverse
      relationship between combat exposure and PTSD might be explained by the selection
      of potential combatants among all recruits and by the heightened preparedness to
      military life stressors.

PMID- 28492376
TI  - Cannabis and Alcohol Abuse Among First Psychotic Episode Inpatients.
AB  - BACKGROUND: Psychoactive substance abuse, which includes abuse of alcohol and
      street drugs, is common among first-episode psychosis patients, but the
      prevalence of cannabis abuse is particularly high. However, there have been very
      few reported studies concerning the occurrence of psychoactive substance abuse
      among first-episode psychotic individuals using standard toxicological testing.
      We study the prevalence of cannabis and alcohol abuse among first
      psychoticepisode inpatients as well as compare the demographic, diagnostic, and
      psychopathological profiles of substance abusers versus nonusers. METHODS:
      Subjects were recruited from the Jerusalem Mental Health Center between 2012 and
      2014. Ninety-one consecutively admitted psychiatric patients diagnosed using the
      DSM-IV criteria with a first psychotic episode due to schizophrenia,
      schizophreniform disorder, bipolar disorder, brief psychotic episode, and
      psychosis NOS disorder entered the study. The diagnoses of schizophrenia (all
      types), psychosis NOS disorder, brief psychotic episode, and schizophreniform
      disorder were categorized as "only psychosis" and those of bipolar disorder manic
      episode with psychotic features (congruent and incongruent) and severe depression
      with psychotic features were categorized as "predominantly affective symptoms."
      Urine tests for tetrahydrocannabinol (THC) were performed during the first 48
      hours of admission, and likewise self-report questionnaires were administered.
      Alcohol abuse and dependence were diagnosed by self-report. RESULTS: Of the 91
      subjects in the study, 49 (53.8%) did not abuse any illegal psychoactive
      substance. Twenty patients (22%) abused only cannabis; 14 (15.4%) abused cannabis
      and another psychoactive substance; 54 (59.3%) of the subjects reported no
      alcohol abuse; 33 (36.3%) reported occasional drinking (between two and ten times
      a month); and 4 (4.4%) reported continuous repeated drinking (more than ten times
      a month). There was no correlation between the demographic characteristics and
      the abuse of cannabis. Two-thirds of the "predominantly affective symptoms"
      subjects were positive for THC, whereas only a third of the "only psychosis"
      subjects screened positive for THC. CONCLUSIONS: The percentage of cannabis and
      alcohol abuse in the study population is much higher than one would expect to see
      in the general Israeli population (according to the Knesset Research Department
      7.6-10.2% of the adult Israeli population abuse cannabis). Different patterns of
      cannabis abuse among "predominantly affective" and "psychotic only" patients may
      lend credence to the preferential use of a specific substance per diagnosis.

PMID- 28492377
TI  - The Association between Obesity and Symptoms of Psychopathology and its
      Relationship with Sedentary Behavior and Mediterranean Diet.
AB  - BACKGROUND: Recent research indicates an association between obesity and symptoms
      of psychopathology, the nature of which remains obscure. This study examined the
      confounding role of behavioral factors on this association. METHOD: One hundred
      and forty-two overweight/obese subjects who sought treatment for obesity, of both
      genders (51 males and 91 females), 18 to 64 years old and 139 normal-weight
      controls of both genders (41 males and 98 females), 18 to 63 years old, were
      enrolled in this study. We measured psychopathology features, using the Symptom
      Checklist 90-Revised (SCL-90-R), dietary habits, using the MedDietScore (MDS)
      questionnaire, and physical activity, using the International Physical Activity
      Questionnaire (IPAQ). A series of regression models were used to estimate the
      mediation of dietary patterns and physical activity on the obesity
      psychopathology association. RESULTS: The associations between obesity and
      depression (beta=0.32/beta=0.15), obsession-compulsion (beta=0.03/beta=-0.13),
      anxiety (beta=-0.25/beta=-0.12), interpersonal sensitivity (beta=0.08/beta=-0.04)
      and psychoticism (beta=-0.01/ beta=0.025) are accounted for by sedentary behavior
      and Mediterranean diet. CONCLUSIONS: Our data suggest that modifiable behavioral
      factors such as sedentary time and dietary patterns positively affect the
      association between obesity and symptoms of psychopathology.

PMID- 28492378
TI  - Short-term Focused Inpatient Treatment Combined with Sensory Regulation of Sexual
      Trauma Victims - Summary of 100 First Hospitalizations.
AB  - BACKGROUND: Treatment of sexual trauma victims may be fraught with crises. In
      situations of de-compensation, the frequency of suicide attempts is high, and
      ambulatory treatment may not always provide the required response. In extreme
      cases, either in close proximity to the sexual offence or even years later, a
      more intense intervention is needed. This includes removing sexual trauma victims
      from their daily lives and hospitalization. Caregivers debate the type of
      hospitalization needed and the best type of treatment in times of decompensation
      and dissociation. METHOD: This paper depicts a hospitalization model in Israel
      that has been created to provide a unique and focused solution for sexual trauma
      victims. The psychological principle of the hospitalization is based on Mann's
      shortterm dynamic psychotherapy method. The patients are integrated in an acute
      psychiatric ward in which a variety of psychopathologies, men and women, are
      treated. RESULTS: The paper summarizes findings and understandings from the first
      100 hospitalizations. The author's main conclusion is that sexual trauma victims
      need a focused specialized treatment plan to best deal with their complex issues
      and that hospitalization should be minimized to two weeks. CONCLUSIONS: The
      author's main recommendation is that funding must be allocated for hospital beds
      for sexual trauma victims in each region in the country to produce adequate
      continuity of care for these patients.

PMID- 28492379
TI  - Psychological Factors Associated with Emotional Distress among Palestinian Arabs
      from East Jerusalem Accessing Psychiatric Care in Israel.
AB  - BACKGROUND: The Palestinian population residing in East Jerusalem is
      characterized by high rates of poverty and unemployment and is subject to
      discrimination in various forms, including infrastructure of mental health
      services. Little is known about the help seeking needs and practices of East
      Jerusalem residents. METHOD: We examined socio-demographic and clinical
      characteristics of a consecutive sample Palestinian residents from East Jerusalem
      (N=50) who accessed a specially assigned psychiatric clinic in Israel. In
      addition, we examined the psychological factors associated with emotional
      distress among these service-users upon entry to care. Participants completed a
      survey in Arabic that included a socio-demographic questionnaire and measures
      assessing emotional distress, perceived exposure to discrimination and social
      support, and mental health stigma. RESULTS: Participants reported high levels of
      emotional distress. Female gender, low socioeconomic status, higher perceived
      exposure to discrimination and higher perceived social support were associated
      with increased emotional distress. CONCLUSIONS: Findings add to the scarce body
      of knowledge on specific mental health characteristics of East Jerusalem
      Palestinian residents.

PMID- 28492380
TI  - Religious-Ethnic Differences in Prevalence and Correlates of Suicidal Ideation
      and Attempts Among Israeli Vocational Education Students.
AB  - BACKGROUND: The current study is the first to examine serious suicidal ideation,
      suicide attempts and psychological distress among students belonging to different
      religious-ethnic groups attending VET high schools. METHOD: 3,553 students
      studying in the VET high schools completed a self-report survey. The survey
      evaluated serious suicidal ideation, suicide attempts, depression, anxiety,
      somatization, self-efficacy, belonging and sociodemographic variables. RESULTS:
      Students coming from minority groups (Arab Muslim, Bedouin Arab Muslim, Druze)
      are more likely to have seriously considered suicide or attempted suicide
      compared to their Jewish counterparts, with the exception of Christian Arabs.
      Bedouin Arab Muslim students were more susceptible to suicide ideation and
      attempts upon high depression levels. CONCLUSIONS: Minority youth at VET schools
      are at greater risk of experiencing suicidal ideation and attempting suicide
      compared to non-minority students. The education system must be highly alert to
      depressive symptoms among Bedouin Arab Muslim students since they may pose a
      greater risk to develop into suicidal ideation and attempt.

PMID- 28492381
TI  - Cultural Impact on SAD: Social Anxiety Disorder among Ethiopian and Former Soviet
      Union Immigrants to Israel, in Comparison to Native-born Israelis.
AB  - BACKGROUND: Social Anxiety Disorder (SAD) is linked to social norms and role
      expectations which are culture dependent, such as the construal of one's self as
      independent or interdependent in relation to others. The current study is the
      first to examine SAD symptoms among Ethiopian and former Soviet Union immigrants
      to Israel compared to a sample of native Israelis. We investigated the
      relationship between SAD, ethnicity and independent/ interdependent self
      construals. METHODS: A total of 261 students (151 native-born Israelis, 60
      Ethiopian immigrants and 50 students from the former USSR) were administrated the
      Liebowitz Scale (LSAS), the Self-construal Scale (SCS), Beck Depression Inventory
      (BDI) and a socio-demographic questionnaire. RESULTS: Ethiopians exhibited
      highest SAD scores while no differences were found between the FSU immigrants and
      native-born Israelis. Additionally, Ethiopians and native-born Israeli students
      exhibited similar high interdependence scores. Finally, SAD scores were predicted
      by gender, origin, independent and interdependent self-construals. CONCLUSION:
      Immigration per se is not a universal risk factor of SAD and ethnological
      cultural factors do contribute specifically to SAD. A possible psychological
      mediator between culture and the susceptibility to SAD are the interdependence
      and independent self-construals. When treating immigrants, clinicians and health
      care providers are advised to consider the effect of cultural influence on the
      mental well-being and integration process of immigrants in to their host country.

PMID- 28492382
TI  - Assessing the Use of the Child Attachment Interview in a Sample of Israeli Jewish
      Children.
AB  - BACKGROUND: This manuscript assesses the use of the Child Attachment Interview
      (CAI) in a sample of Israeli Jewish children in middle childhood in order to add
      to empirical data on this measure. METHOD: Forty-one children between the ages of
      7 and 13 were consecutively recruited to the study. The clinical sample included
      29 children diagnosed with anxiety disorder, major depression or ADHD. The Father
      Focused Referral (FFR) sample included 12 children whose father was unavailable
      to them. Participants were administered the CAI and coded by certified personnel.
      RESULTS: 81.4% concordance was found between maternal and paternal secure
      insecure attachment classifications in the clinical sample; 100% of the children
      in the FFR group were classified as insecurely attached to their fathers
      suggesting convergent validity for the classification of father attachment; 45.4%
      of the children in the FFR sample were also classified as insecurely attached to
      their mothers, pointing to the difference that can be found between the two
      parental attachment classifications in relevant cases, and therefore to
      sufficient discriminant validity between the two classifications. CONCLUSIONS:
      The clinical sample concordance rate, which was lower than in previous studies,
      indicates that parental concordance rates should be further investigated using
      different samples and countries. The study's findings regarding the difference
      that can be found between parental attachment classifications show the
      instrument's relevance in cases which the parental representations may differ. In
      these cases, using an instrument that does not examine the attachment toward both
      parents might not suffice. Study limitations and further implications are
      discussed.

PMID- 28492383
TI  - Parent-child Interaction Treatment for Preschoolers with Feeding Disorders.
AB  - BACKGROUND: This study examined the immediate outcome of Feeding Disorders (FD)
      in preschoolers referred to the family treatment program Cerco Asilo. METHOD: 21
      children (mean age [SD=1]: 39 months [1]; range 9-65 months) with a diagnosis of
      FD were included in the treatment for 24 weeks. Specifically, seven subjects were
      diagnosed with Infantile Anorexia (IA), nine subjects with Sensory Food Aversion
      (SFA), and five subjects with Feeding Disorder of Caregiver-Infant Reciprocity
      (FDCIR). RESULTS: The great majority of patients with SFA and with FDCIR resolved
      the FD, whereas children with IA did not respond well to the treatment.
      LIMITATIONS: The study's main limitations are the relatively small sample size,
      and the lack of a control group. CONCLUSIONS: Findings suggest that changes in
      the parentchild relationship could generally promote FD resolution, other than
      IA. These data may have implications for clinical practice suggesting the need to
      develop ad hoc intervention protocols tailored to children with IA and their
      families.

PMID- 28492384
TI  - Effect of Dexmedetomidine and Propofol on Basal Ganglia Activity in Parkinson
      Disease: A Controlled Clinical Trial.
AB  - BACKGROUND: Deep brain stimulation electrodes can record oscillatory activity
      from deep brain structures, known as local field potentials. The authors'
      objective was to evaluate and quantify the effects of dexmedetomidine (0.2
      MUg.kg.h) on local field potentials in patients with Parkinson disease undergoing
      deep brain stimulation surgery compared with control recording (primary outcome),
      as well as the effect of propofol at different estimated peak effect site
      concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 MUg/ml) from control recording.
      METHODS: A nonrandomized, nonblinded controlled clinical trial was carried out to
      assess the change in local field potentials activity over time in 10 patients
      with Parkinson disease who underwent deep brain stimulation placement surgery (18
      subthalamic nuclei). The relationship was assessed between the activity in nuclei
      in the same patient at a given time and repeated measures from the same nucleus
      over time. RESULTS: No significant difference was observed between the relative
      beta power of local field potentials in dexmedetomidine and control recordings (
      7.7; 95% CI, -18.9 to 7.6). By contrast, there was a significant decline of 12.7%
      (95% CI, -21.3 to -4.7) in the relative beta power of the local field potentials
      for each increment in the estimated peak propofol concentrations at the effect
      site relative to the control recordings. CONCLUSIONS: Dexmedetomidine (0.2
      MUg.kg.h) did not show effect on local field potentials compared with control
      recording. A significant deep brain activity decline from control recording was
      observed with incremental doses of propofol.

PMID- 28492386
TI  - From the Editor.

PMID- 28492385
TI  - The Prognostic Value of Central Venous-to-Arterial CO2 Difference/Arterial
      Central Venous O2 Difference Ratio in Septic Shock Patients with Central Venous
      O2 Saturation >=80.
AB  - BACKGROUND: It is a great challenge for physician to assess the relationship
      between O2 delivery and O2 consumption in septic shock patients with high ScvO2.
      Recently, the venous-to-arterial CO2 difference/arterial-central venous O2
      difference ratio (P(v-a)CO2/C(a-v)O2) has shown potential for reflecting
      anaerobic metabolism. Therefore, we evaluated the value of using the P(v
      a)CO2/C(a-v)O2 ratio to predict mortality and assess anaerobic metabolism in
      septic shock patients with high ScvO2 (>= 80%). METHODS: This was a clinical
      investigation of septic shock patients on the P(v-a)CO2/C(a-v)O2 ratio in the
      intensive care unit (ICU) department. The patients' arterial and central venous
      blood gas levels were measured simultaneously at enrollment (T0) and 24 h (T24)
      after resuscitation. RESULTS: A total of 61 patients with high ScvO2 at T24 after
      resuscitation were selected for analysis. The ICU mortality rate in the septic
      shock patients was 20% (12/61). The nonsurvivors had a significantly higher P(v
      a)CO2, P(v-a)CO2/C(a-v) O2 ratio, arterial lactate level and lower lactate
      clearance at T24 after resuscitation. The P(v-a)CO2/C(a-v)O2 ratio had the
      biggest the areas under the receiver operating characteristic (AUC) for
      predicting ICU mortality. For predicting ICU mortality, a threshold of P(v
      a)CO2/C(a-v)O2 ratio >=1.6 was associated with a sensitivity of 83% and a
      specificity of 63%. Multivariate analysis showed P(v-a)CO2/C(a-v)O2 ratio at both
      T0 (RR 5.597, P = 0.024) and T24 (RR 5.812, P = 0.031) was an independent
      predictor of ICU mortality. Including the ratio into the regression model showed
      a bigger AUC than without the ratio (0.886 vs. 0.833). CONCLUSIONS: The P(v
      a)CO2/C(a-v)O2 ratio is an independent predictor of ICU mortality in septic shock
      patients with high ScvO2 after resuscitation. It is worthy of consideration to
      recruit microcirculation to correct the high ratio in high ScvO2 case.

PMID- 28492387
TI  - Letter to the Editor.

PMID- 28492388
TI  - Letter to the Editor.

PMID- 28492389
TI  - "What About the Next Generation That's Coming?": The Recontextualization of
      Mothering Post-Refugee Resettlement.
AB  - The purpose of this analysis was to explore the recontextualization of mothering
      in Karen refugees from Burma. We collected ethnographic data over an 11-month
      period with a cohort of 12 Karen women postresettlement. Using Spradley's and
      tools of critical discourse analysis, we interpreted the migration narratives of
      women, in particular, experiences they shared as mothers. These narratives were
      grounded in the space of cultural difference; thus, we engaged hybridity as a
      theoretical frame. Findings reflect the negotiation of mothering practices within
      the norms, structures, and policies of the country of resettlement. We identified
      the spaces of transformation a woman constructed to usher change while sustaining
      a connection between herself, her culture, and her children.

PMID- 28492390
TI  - Challenges in tuberculosis/HIV management in a country with a concentrated HIV
      epidemic.

PMID- 28492391
TI  - Hepatitis C virus drives increased type I interferon-associated impairments
      associated with fibrosis severity in antiretroviral treatment-treated HIV-1
      hepatitis C virus-coinfected individuals.
AB  - BACKGROUND: Viral coinfections might contribute to the increased immune
      activation and inflammation that persist in antiretroviral treatment (ART)
      treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV)
      coinfection contributes to such alterations by impairing the plasmacytoid
      dendritic cell (pDC) IFNalpha/TLR7 pathway in a highly homogeneous group of ART
      treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected
      patients with fully suppressive ART were included, 15 of whom being HCV
      coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease,
      and 13 control healthy donors. Cellular activation, plasma levels of inflammatory
      cytokines and pDC transcriptome associated with IFNalpha/TLR7 pathway were
      characterized. RESULTS: Higher plasma levels of type-I interferon (IFN)
      associated cytokines [interferon gamma-induced protein 10 (IP-10), MIP-1beta, IL
      8 and IFN-inducible T-cell alpha chemoattractant) were observed in HIV-1-HCV
      coinfected than in HIV-1-monoinfected patients (P = 0.0007, 0.028, 0.028 and
      0.035, respectively). The pDCs and T cells displayed a more exhausted (LAG-3+ and
      CD57+, respectively) phenotype. The pDC IFNalpha pathway (defined by
      phosphorylated STAT1 expression) was constitutively activated in all patients,
      irrespective of HCV coinfection. Expression of interferon-stimulated genes (ISGs)
      EI2AK2, ISG15, Mx1 and IFI44 was increased in pDCs from HIV-1-HCV-coinfected
      individuals and was correlated with fibrosis score (Fibroscan, www.echosens.com,
      Paris, France and aspartate-aminotransferase/platelet-ratio index score, P =
      0.026 and 0.019, respectively). Plasma levels of IP-10, STAT1 expression in pDCs
      and Mx1 mRNA levels in pDCs decreased after interferon-free anti-HCV treatment.
      CONCLUSION: HCV replication appears to drive increases in type-I IFN-associated
      inflammation and ISGs expression in pDCs, in association with fibrosis severity
      in ART-treated HIV-1-infected patients with mild-to-moderate fibrosis.
      Preliminary results indicate reduction of these alterations with earlier
      interferon-free anti-HCV treatment in those patients.

PMID- 28492392
TI  - Predictors of estimated glomerular filtration rate progression, stabilization or
      improvement after chronic renal impairment in HIV-positive individuals.
AB  - OBJECTIVES: The objectives of this analysis were to investigate predictors of
      progression, stabilization or improvement in estimated glomerular filtration rate
      (eGFR) after development of chronic renal impairment (CRI) in HIV-positive
      individuals. DESIGN: Prospective observational study. METHODS: The Data
      Collection on Adverse events of Anti-HIV Drugs (D:A:D) study participants
      progressing to CRI defined as confirmed, at least 3 months apart, and eGFR 70
      ml/min per 1.73 m or less were included in the analysis. The median of all eGFRs
      measured 24-36 months post-CRI was compared with the median eGFR defining CRI,
      and changes were grouped into improvement (>+10 ml/min per 1.73 m), stabilization
      (-10 to +10 ml/min per 1.73 m) and progression (<-10 ml/min per 1.73 m). Adjusted
      polynomial regression models assessed odds of better eGFR outcomes after CRI,
      assuming that eGFR improvement is better than stabilization which in turn is
      better than progression. RESULTS: Of 2006 individuals developing CRI, 21%
      subsequently improved eGFR, 67% stabilized and 12% progressed. Individuals
      remaining on tenofovir (TDF) or atazanavir boosted with ritonavir (ATV/r) 24
      months post-CRI had worse eGFR outcomes compared with those unexposed [TDF: 0.47
      (0.35-0.63) and ATV/r: 0.63 (0.48-0.82)]. Individuals off TDF for 12-24 months
      [0.75 (0.50-1.13)] or off ATV/r for more than 12 months [1.17 (0.87-1.57)] had
      similar eGFR outcomes as those unexposed to these antiretrovirals. Older age,
      hypertension, later date of CRI and diabetes were associated with worse eGFR
      outcomes. CONCLUSION: Current TDF and ATV/r use after a diagnosis of CRI was
      associated with worse eGFR outcomes. In contrast, TDF and ATV/r discontinuation
      lead to similar longer term eGFR outcomes as in those unexposed, suggesting that
      these drug-associated eGFR declines may be halted or reversed after their
      cessation.

PMID- 28492393
TI  - Long-term alcohol use patterns and HIV disease severity.
AB  - OBJECTIVE: We examined the relationship between alcohol use trajectories and HIV
      disease severity among men and women participating in the Veterans Aging Cohort
      Study (VACS). DESIGN: Prospective cohort of HIV-infected persons in care at eight
      US Veterans Health Administration sites. METHODS: Between 2002 and 2010, we
      assessed alcohol consumption annually using the alcohol use disorders
      identification test-consumption (AUDIT-C). HIV disease severity was ascertained
      using the VACS index, a validated measure of morbidity and all-cause mortality.
      We examined the relationship between alcohol use and HIV disease severity
      patterns using joint trajectory modeling. Alcohol use trajectories were validated
      using phosphatidylethanol - a biomarker of alcohol consumption - measured between
      2005 and 2006 among a subset of participants. We examined associations between
      membership in alcohol use and VACS index trajectories using multinomial
      regression. RESULTS: Among eligible participants, we identified four alcohol
      consumption trajectories: abstainers (24% of the sample), lower risk (44%),
      moderate risk (24%), and higher risk drinkers (8%). Alcohol use trajectories were
      highly correlated with phosphatidylethanol (Cramer's V = 0.465, P < 0.001): mean
      concentrations were 4.4, 17.8, 57.7, and 167.6 ng/ml in the abstainer, lower
      risk, moderate risk, and higher risk groups, respectively. Four VACS index
      trajectories were identified: low (2%), moderate (46%), high (36%), and extreme
      (16%). Higher risk drinkers were most common in the extreme VACS index group, and
      were absent in the low index group. In multivariable analysis, the association
      between alcohol use and VACS index trajectory membership remained significant (P
      = 0.002). CONCLUSION: Alcohol use trajectories characterized by persistent
      unhealthy drinking are associated with more advanced HIV disease severity among
      HIV-infected veterans in the United States.

PMID- 28492394
TI  - Sub-Saharan African migrants have slower initial CD4+ cell recovery after
      combined antiretroviral treatment initiation than French natives.
AB  - OBJECTIVE: Poorer immunologic responses to combined antiretroviral treatment
      (cART) have been reported among sub-Saharan African (SSA) migrants than among
      native Europeans. We studied whether differences in CD4 cell recovery between
      French natives and SSA migrants starting first-line cART could be explained by
      differences in socioeconomic conditions, inflammatory marker levels, and other
      established determinants. METHODS: We compared 319 French natives and 175 SSA
      migrants (ANRS-COPANA cohort). Clinical, biological, and socioeconomic data
      (education, employment, income, and cohabiting partnership) were recorded at
      regular visits. A piecewise linear mixed-effects model was used to analyze CD4
      cell count kinetics on cART. RESULTS: Compared with French natives, SSA migrants
      were more frequently women, younger, less educated, living in more adverse
      conditions, and had more frequent symptoms of depression. The rate of CD4 cell
      recovery during the first 4 months on cART was significantly slower in SSA
      migrants, despite a similar virologic response, but did not differ significantly
      thereafter. The mean CD4 cell count rose from 251 cells/MUl at baseline to 508
      cells/MUl at 36 months in migrants, and from 308 to 623 cells/MUl in natives
      (additional mean gain of 58 cells/MUl in natives). The difference persisted after
      adjustment for clinical, updated socioeconomic, and living conditions (-0.40?CD4
      cells/month, P = 0.04); 25-hydroxyvitamin D, monocyte chemoattractant protein-1
      and soluble tumor necrosis factor receptor 1 (sTNFR1) levels were lower in SSA
      migrants, but only sTNFR1 contributed to the difference in CD4 slope. CONCLUSION:
      Initial CD4 cell recovery on cART was slower among SSA migrants than among French
      natives. This difference was not explained by established clinical and biological
      determinants or by socioeconomic status.

PMID- 28492395
TI  - HIV prevention: response to pre-exposure prophylaxis failure with tenofovir
      disoproxil.

PMID- 28492396
TI  - Preexposure prophylaxis failure with tenofovir disoproxil.

PMID- 28492397
TI  - Post-treatment control in an adult with perinatally acquired HIV following
      cessation of antiretroviral therapy.

PMID- 28492398
TI  - Chronic hepatitis E in HIV/HBV coinfected patient: lack of power of sofosbuvir
      ribavirin.

PMID- 28492399
TI  - Acute Kidney Injury After Pediatric Cardiac Surgery: A Secondary Analysis of the
      Safe Pediatric Euglycemia After Cardiac Surgery Trial.
AB  - OBJECTIVES: To understand the effect of tight glycemic control on cardiac surgery
      associated acute kidney injury. DESIGN: Secondary analysis of data from the Safe
      Pediatric Euglycemia after Cardiac Surgery trial of tight glycemic control versus
      standard care. SETTING: Pediatric cardiac ICUs at University of Michigan, C.S.
      Mott Children's Hospital, and Boston Children's Hospital. PATIENTS: Children 0-36
      months old undergoing congenital cardiac surgery. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Cardiac surgery-associated acute kidney injury was
      assigned using the Acute Kidney Injury Network criteria with the modification
      that a greater than 0.1 mg/dL increase in serum creatinine was required to assign
      cardiac surgery-associated acute kidney injury. We explored associations between
      cardiac surgery-associated acute kidney injury and tight glycemic control and
      clinical outcomes. Of 799 patients studied, cardiac surgery-associated acute
      kidney injury occurred in 289 patients (36%), most of whom had stage II or III
      disease (72%). Cardiac surgery-associated acute kidney injury rates were similar
      between treatment groups (36% vs 36%; p = 0.99). Multivariable modeling showed
      that patients with cardiac surgery-associated acute kidney injury were younger (p
      = 0.002), underwent more complex surgery (p = 0.005), and had longer
      cardiopulmonary bypass times (p = 0.002). Cardiac surgery-associated acute kidney
      injury was associated with longer mechanical ventilation and ICU and hospital
      stays and increased mortality. Patients at University of Michigan had higher
      rates of cardiac surgery-associated acute kidney injury compared with Boston
      Children's Hospital patients (66% vs 15%; p < 0.001), but University of Michigan
      patients with cardiac surgery-associated acute kidney injury had shorter time to
      extubation and ICU and hospital stays compared with Boston Children's Hospital
      patients. CONCLUSIONS: Tight glycemic control did not reduce the cardiac surgery
      associated acute kidney injury rate in this trial cohort. We observed significant
      differences in cardiac surgery-associated acute kidney injury rates between the
      two study sites, and there was a differential effect of cardiac surgery
      associated acute kidney injury on clinical outcomes by site. These findings
      warrant further investigation to identify causal variation in perioperative
      practices that affect cardiac surgery-associated acute kidney injury
      epidemiology.

PMID- 28492400
TI  - Epinephrine Auto-Injector Versus Drawn Up Epinephrine for Anaphylaxis Management:
      A Scoping Review.
AB  - OBJECTIVE: Anaphylaxis is a life-threatening event. Most clinical symptoms of
      anaphylaxis can be reversed by prompt intramuscular administration of epinephrine
      using an auto-injector or epinephrine drawn up in a syringe and delays and errors
      may be fatal. The aim of this scoping review is to identify and compare errors
      associated with use of epinephrine drawn up in a syringe versus epinephrine auto
      injectors in order to assist hospitals as they choose which approach minimizes
      risk of adverse events for their patients. DATA SOURCES: PubMed, Embase, CINAHL,
      Web of Science, and the Cochrane Library were searched using terms agreed to a
      priori. STUDY SELECTION: We reviewed human and simulation studies reporting
      errors associated with the use of epinephrine in anaphylaxis. There were multiple
      screening stages with evolving feedback. DATA EXTRACTION: Each study was
      independently assessed by two reviewers for eligibility. Data were extracted
      using an instrument modeled from the Zaza et al instrument and grouped into
      themes. DATA SYNTHESIS: Three main themes were noted: 1) ergonomics, 2) dosing
      errors, and 3) errors due to route of administration. Significant knowledge gaps
      in the operation of epinephrine auto-injectors among healthcare providers,
      patients, and caregivers were identified. For epinephrine in a syringe, there
      were more frequent reports of incorrect dosing and erroneous IV administration
      with associated adverse cardiac events. For the epinephrine auto-injector,
      unintentional administration to the digit was an error reported on multiple
      occasions. CONCLUSIONS: This scoping review highlights knowledge gaps and a
      diverse set of errors regardless of the approach to epinephrine preparation
      during management of anaphylaxis. There are more potentially life-threatening
      errors reported for epinephrine drawn up in a syringe than with the auto
      injectors. The impact of these knowledge gaps and potentially fatal errors on
      patient outcomes, cost, and quality of care is worthy of further investigation.

PMID- 28492401
TI  - Renal Function Follow-Up and Renal Recovery After Acute Kidney Injury in
      Critically Ill Children.
AB  - OBJECTIVES: To evaluate factors associated with renal recovery from acute kidney
      injury in critically ill children and the extent to which serum creatinine is
      measured before discharge. DESIGN: Retrospective cohort study. SETTING: Two PICUs
      at tertiary centers in Montreal, QC, Canada. PATIENTS: Children (< 18 yr old)
      admitted to the PICU between 2003 and 2005. Patients with end-stage renal
      disease, no healthcare number, died during admission, or admitted postcardiac
      surgery were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute
      kidney injury was defined using internationally accepted criteria (Kidney
      Disease: Improving Global Outcomes). Two renal recovery outcomes commonly used in
      the literature were evaluated: hospital discharge serum creatinine less than 1.5
      and less than 1.15 times baseline. Proportions of patients with 1) serum
      creatinine measurements between PICU and hospital discharge and 2) renal recovery
      were calculated. Univariate and multivariate analyses were performed to determine
      factors associated with serum creatinine monitoring and nonrecovery after acute
      kidney injury. Of 2,033 patients included, 829 (40.8%) had serum creatinine
      measurements between PICU and hospital discharge. The odds of having a discharge
      serum creatinine measurement increased with acute kidney injury severity (stages
      1, 2, 3 adjusted odds ratio [95% CI]: 1.49 [1.03-2.15], 2.52 [1.40-4.54], 7.87
      [3.16-19.60], respectively). Acute kidney injury recovery was 92.5% when defined
      as serum creatinine less than 1.5 times baseline versus 75.9% when defined as
      less than 1.15 times baseline (p < 0.001). Stage 3 acute kidney injury was
      associated with having a discharge serum creatinine greater than or equal to 1.5
      times baseline (adjusted odds ratio = 3.51 [1.33-9.19]). CONCLUSIONS: Less than
      half the PICU population had serum creatinine measured before hospital discharge.
      More severe acute kidney injury was associated with higher likelihood of serum
      creatinine monitoring and lower probability of acute kidney injury recovery.
      Future research should address knowledge translation on post-PICU acute kidney
      injury follow-up before hospital discharge.

PMID- 28492402
TI  - Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical
      Criteria for Sepsis in Children?
AB  - OBJECTIVE: A recent task force has proposed the use of Sequential Organ Failure
      Assessment in clinical criteria for sepsis in adults. We sought to evaluate the
      predictive validity for PICU mortality of the Pediatric Logistic Organ
      Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on
      day 1 in children with suspected infection. DESIGN: Secondary analysis of the
      database used for the development and validation of the Pediatric Logistic Organ
      Dysfunction-2. SETTINGS: Nine university-affiliated PICUs in Europe. PATIENTS:
      Only children with hypotension-low systolic blood pressure or low mean blood
      pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were
      considered in shock. MEASUREMENTS AND MAIN RESULTS: We developed the quick
      Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia,
      hypotension, and altered mentation (Glasgow < 11): one point for each variable
      (range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under
      receiver operating characteristic curve-95% CI) and calibration (goodness of fit
      test) of the scores were studied. This study included 862 children with suspected
      infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve
      of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96)
      in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic
      blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean
      blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49,
      respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater
      than or equal to 8 reflected an overall risk of mortality greater than or equal
      to 9.3% in children with suspected infection. Area under the curve of the quick
      Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with
      systolic blood pressure or mean blood pressure; calibration p value was 0.89 and
      0.72, respectively. A score greater than or equal to 2 reflected a mortality risk
      greater than or equal to 19.8% with systolic blood pressure and greater than or
      equal to 15.9% with mean blood pressure. CONCLUSION: Among children admitted to
      PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on
      day 1 was highly predictive of PICU mortality suggesting its use to standardize
      definitions and diagnostic criteria of pediatric sepsis. Further studies are
      needed to determine the usefulness of the quick Pediatric Logistic Organ
      Dysfunction-2 score on day 1 outside of the PICU.

PMID- 28492403
TI  - Pediatric In-Hospital Acute Respiratory Compromise: A Report From the American
      Heart Association's Get With the Guidelines-Resuscitation Registry.
AB  - OBJECTIVES: The main objectives of this study were to describe in-hospital acute
      respiratory compromise among children (< 18 yr old), and its association with
      cardiac arrest and in-hospital mortality. DESIGN: Observational study using
      prospectively collected data. SETTING: U.S. hospitals reporting data to the "Get
      With The Guidelines-Resuscitation" registry. PATIENTS: Pediatric patients (< 18
      yr old) with acute respiratory compromise. Acute respiratory compromise was
      defined as absent, agonal, or inadequate respiration that required emergency
      assisted ventilation and elicited a hospital-wide or unit-based emergency
      response. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome
      was in-hospital mortality. Cardiac arrest during the event was a secondary
      outcome. To assess the association between patient, event, and hospital
      characteristics and the outcomes, we created multivariable logistic regressions
      models accounting for within-hospital clustering. One thousand nine hundred fifty
      two patients from 151 hospitals were included. Forty percent of the events
      occurred on the wards, 19% in the emergency department, 25% in the ICU, and 16%
      in other locations. Two hundred eighty patients (14.6%) died before hospital
      discharge. Preexisting hypotension (odds ratio, 3.26 [95% CI, 1.89-5.62]; p <
      0.001) and septicemia (odds ratio, 2.46 [95% CI, 1.52-3.97]; p < 0.001) were
      associated with increased mortality. The acute respiratory compromise event was
      temporally associated with a cardiac arrest in 182 patients (9.3%), among whom
      46.2% died. One thousand two hundred eight patients (62%) required tracheal
      intubation during the event. In-hospital mortality among patients requiring
      tracheal intubation during the event was 18.6%. CONCLUSIONS: In this large,
      multicenter study of acute respiratory compromise, 40% occurred in ward settings,
      9.3% had an associated cardiac arrest, and overall in-hospital mortality was
      14.6%. Preevent hypotension and septicemia were associated with increased
      mortality rate.

PMID- 28492405
TI  - A Case-Control Analysis of Postoperative Fluid Balance and Mortality After
      Pediatric Cardiac Surgery.
AB  - OBJECTIVES: A positive fluid balance after cardiac surgery may be associated with
      poor outcomes; however, previous studies looking at this association have been
      limited by the number of deaths in the study population. Our primary aim was to
      determine the relationship between postoperative cumulative fluid balance and
      mortality in cardiac surgical patients. Secondary aims were to study the
      association between fluid balance and duration of mechanical ventilation,
      intensive care and hospital length of stay. DESIGN: Case-control study. SETTING:
      A 30-bed multidisciplinary PICU. PATIENTS: All patients admitted to the PICU
      following cardiac surgery from 2010 to 2014. INTERVENTIONS: Deaths during PICU
      admission following cardiac surgery (cases) were matched 1:3 with children who
      survived to PICU discharge (controls) using the following criteria: age at
      surgery (within a 20% age range), Risk Adjusted Congenital Heart Surgery (RACHS
      1) category, and year of admission. MEASUREMENTS AND MAIN RESULTS: Of 1,996
      eligible children, 46 died (2.3%) of whom 45 (98%) were successfully matched.
      Cumulative fluid balance on days 2 and 7 was not associated with PICU mortality.
      On multivariable analysis, factors associated with mortality were cardiopulmonary
      bypass time (per 10-min increase, odds ratio [95% CI], 1.06 [1.00-1.12]; p =
      0.03), extracorporeal membrane oxygenation requirement within 3 days (46.6 [9.47
      230.11]; p < 0.001), peak serum chloride (mmol/L) in the first 48 hours (1.12
      [1.01-1.23]), and time to start peritoneal dialysis after surgery (in comparison
      to no peritoneal dialysis, odds ratio [95% CI] in those started on early
      peritoneal dialysis was 1.07 [0.33-3.41]; p = 0.90 and in late peritoneal
      dialysis 3.65 [1.21-10.99]; p = 0.02). Children with cumulative fluid balance
      greater than or equal to 5% by day 2 spent longer on mechanical ventilation
      (median [interquartile range], 211 hr [97-539] vs 93 hr [34-225]; p <0.001), in
      PICU (11 d [8-26] vs 6 [3-13]; p < 0.001) and in hospital (22 d [13-39] vs 14 d
      [8-30]; p = 0.001). CONCLUSIONS: Early fluid overload is not associated with
      mortality. However, it is associated with increased duration of mechanical
      ventilation and PICU length of stay. Early peritoneal dialysis commencement
      (compared with late peritoneal dialysis) after surgery was associated with
      decreased mortality.

PMID- 28492407
TI  - The spleen not taken: Differences in management and outcomes of blunt splenic
      injuries in teenagers cared for by adult and pediatric trauma teams in a single
      institution.
AB  - BACKGROUND: Nonoperative management (NOM) of blunt splenic injury, initially
      touted for the care of pediatric patients, has become the standard of care for
      stable trauma patients of all ages. In our institution, trauma patients younger
      than 16 years are managed by the pediatric surgery service and patients 16 years
      or older are managed by the adult trauma service. Angioembolization is routinely
      used for adults with blunt splenic injury but rarely used for pediatric patients.
      A retrospective chart review was performed to determine if more liberal use of
      angioembolization increases the success rate of NOM of blunt splenic injury in
      adolescents. METHODS: Using our institutional trauma registry, we performed a
      retrospective chart review of 13- to 18-year-olds admitted with blunt splenic
      injury from 2007 to 2015. One hundred thirty-three patients were identified; 59
      were 13- to 15-year-olds and cared for by the Pediatric Trauma service, whereas
      74 were 16- to 18-year-olds and cared for by the Adult Trauma service. The
      cohorts were compared with respect to imaging performed, grade of injury, Injury
      Severity Score, presence of active extravasation or pseudoaneurysm, interventions
      performed, blood transfused, intensive care unit days, length of stay,
      complications, and 30-day mortality rates. RESULTS: There were no significant
      differences in Injury Severity Score, incidence of active extravasation or
      pseudoaneurysm identified on computed tomography, or grade of injury between the
      two cohorts. More patients underwent angioembolization in the "adult" group (p =
      0.001) with no difference in the success rate of NOM (p = 0.117). The overall
      failure rate of NOM of high-grade injuries was only 4.1%. CONCLUSION: Failure of
      NOM in high-grade injuries is rare; as a result, the number needed to treat with
      prophylactic angioembolization would be around 37 patients, resulting in undue
      risk to many patients with no therapeutic benefit. No improvement in failure rate
      was seen with aggressive angioembolization, though a larger sample size is needed
      to rule out type 2 error. LEVEL OF EVIDENCE: Therapeutic, level IV.

PMID- 28492404
TI  - Trend and Outcomes of Video Laryngoscope Use Across PICUs.
AB  - OBJECTIVE: Video (indirect) laryngoscopy is used as a primary tracheal intubation
      device for difficult airways in emergency departments and in adult ICUs. The use
      and outcomes of video laryngoscopy compared with direct laryngoscopy has not been
      quantified in PICUs or cardiac ICUs. DESIGN: Retrospective review of
      prospectively collected observational data from a multicenter tracheal intubation
      database (National Emergency Airway Registry for Children) from July 2010 to June
      2015. SETTING: Thirty-six PICUs/cardiac ICUs across the United States, Canada,
      Japan, New Zealand, and Singapore. PATIENTS: Any patient admitted to a PICU or a
      pediatric cardiac ICU and undergoing tracheal intubation. INTERVENTIONS: Use of
      direct laryngoscopy versus video laryngoscopy for tracheal intubation.
      MEASUREMENTS AND MAIN RESULTS: There were 8,875 tracheal intubations reported in
      the National Emergency Airway Registry for Children database, including 7,947
      (89.5%) tracheal intubations performed using direct laryngoscopy and 928 (10.5%)
      tracheal intubations performed using video laryngoscopy. Wide variability in
      video laryngoscopy use exists across PICUs (median, 2.6%; range, 0-55%). Video
      laryngoscopy was more often used in older children (p < 0.001), in children with
      history of a difficult airway (p = 0.01), in children intubated for ventilatory
      failure (p < 0.001), and to facilitate the completion of an elective procedure (p
      = 0.048). After adjusting for patient-level covariates, a secular trend, and site
      level variance, the use of video laryngoscopy significantly increased over a 5
      year period compared with fiscal year 2011 (odds ratio, 6.7; 95% CI, 1.7-26.8 for
      fiscal year 2014 and odds ratio, 11.2; 95% CI, 3.2-38.9 for fiscal year 2015).
      The use of video laryngoscopy was independently associated with a lower
      occurrence of tracheal intubation adverse events (adjusted odds ratio, 0.57; 95%
      CI, 0.42-0.77; p < 0.001) but not with a lower occurrence of severe tracheal
      intubation adverse events (adjusted odds ratio, 0.86; 95% CI, 0.56-1.32; p =
      0.49) or fewer multiple attempts at endotracheal intubation (adjusted odds ratio,
      0.93; 95% CI, 0.71-1.22; p = 0.59). CONCLUSIONS: Using National Emergency Airway
      Registry for Children data, we described patient-centered adverse outcomes
      associated with video laryngoscopy compared with direct laryngoscopy for tracheal
      intubation in the largest reported international cohort of children to date. Data
      from this study may be used to design sufficiently powered prospective studies
      comparing patient-centered outcomes for video laryngoscopy versus direct
      laryngoscopy during endotracheal intubation.

PMID- 28492408
TI  - THE 2017 JOINT INTERNATIONAL CONGRESS OF ILTS, ELITA & LICAGE.

PMID- 28492409
TI  - Papillary Carcinoma Arising in a Thyroglossal Duct Cyst.

PMID- 28492410
TI  - DEXAMETHASONE INTRAVITREAL IMPLANT FOR CHOROIDAL NEOVASCULARIZATION DURING
      PREGNANCY.
AB  - PURPOSE: To describe the management of active choroidal neovascularization (CNV)
      during pregnancy with the use of a dexamethasone intravitreal implant (DXI)
      (Ozurdex). METHODS: Case series of active CNV treated with DXI with at least 12
      month follow-up retrospectively analyzed at 2 high-volume referral centers in
      France. Medical records and multimodal macular imaging were evaluated. RESULTS:
      Three eyes of 3 patients (age 30.0 +/- 3.6 years) were included. One case of
      idiopathic CNV and two cases of CNV secondary to multifocal choroiditis were
      analyzed. Mean follow-up was 20.6 +/- 4.0 months (range, 16-23 months). The DXI
      was given at second trimester of established pregnancy in all cases. Mean central
      retinal thickness decreased from 359 +/- 53 MUm to 301 +/- 17 MUm 1 month after
      DXI and remained stable up to 12 months of follow-up. Visual improvement in all
      cases was observed (mean 10 letters; range, 5-30 letters) 1 month after DXI and
      remained stable/increased up to 12-month follow-up (mean 22 letters; range, 10-30
      letters). All patients had an uneventful prenatal course and delivered a healthy
      full-term infant. CONCLUSION: In the authors' experience, a single DXI revealed
      safe and effective in CNV treatment during pregnancy.

PMID- 28492411
TI  - Advanced glycation end products among patients maintained on antipsychotics.
AB  - The aim of this study was to measure advanced glycation end products (AGEs) among
      participants maintained on antipsychotics using the AGE Reader and to compare
      them with controls from the general population. Participants maintained on
      antipsychotics for at least 6 months were recruited from the Psychiatry
      Department at Rumailah Hospital, Doha, Qatar. Healthy controls were recruited
      from the primary healthcare centers in Doha, Qatar. AGEs of a total of 86
      participants (48 patients and 38 controls) were recorded. Among the group
      maintained on antipsychotics, women, smokers, and Arabs had significantly higher
      AGEs levels compared with men, nonsmokers, and non-Arabs, respectively (P<0.05).
      The levels of AGEs were higher among the group of patients maintained on
      antipsychotics in comparison to controls; however, the difference did not reach
      statistical significance. This is the first study to examine AGEs in patients
      maintained on antipsychotics. Our findings showed that such patients do not
      differ significantly from controls comparing AGEs levels. Future investigations
      might need to consider recruiting a larger sample size using a prospective
      design.

PMID- 28492412
TI  - Patients in prehospital transport to the emergency department: a cohort study of
      risk factors for 7-day mortality.
AB  - BACKGROUND: Ambulance transfer is the first contact with the healthcare system
      for many patients in emergency conditions.We aimed to identify prognostic risk
      factors accessible in the prehospital phase that indicate an increased risk of 7
      day mortality. PATIENTS AND METHODS: We included patients aged 18 years or older,
      transferred by ambulance to the emergency department at Odense University
      Hospital, from 1 April 2012 to 30 September 2014. We carried out multivariate
      logistic regressions, adjusted for age and sex, to describe the relationship
      between vital sign values recorded in the prehospital setting and 7-day
      mortality. RESULTS: A total of 32 076 ambulance transfers were recorded. Of
      these, 20 328 were first-time transfers, including 2692 that received assistance
      from a physician-staffed mobile emergency care unit (MECU). The 7-day mortality
      was 5.3% [95% confidence interval (CI): 5.0-5.6]. The risk of death increased
      with age. The odds ratios (ORs) were 2.0 (95% CI: 1.1-3.5) for ages 30-44 years
      and 7.3 (95% CI: 4.5-11) for ages 45-69 years compared with the 18-29-year-olds.
      All abnormal vital sign values were associated with increased 7-day mortality.
      Glasgow Coma Score of less than 14 had the strongest association (OR: 17, 95% CI:
      14.7-19.7). MECU assistance showed an adjusted OR of 5.3 (95% CI: 4.6-6.1).
      CONCLUSION: The overall 7-day mortality was 5.3%, but differed in the two
      subgroups, with 15.4% in the MECU-assisted ambulance transfers and 3.8% in non
      MECU-assisted transfers. Older age and Glasgow Coma Scores below 14 were the
      strongest of factors associated significantly with 7-day mortality.

PMID- 28492413
TI  - Mentoring in Nursing: An Integrative Review of Commentaries, Editorials, and
      Perspectives Papers.
AB  - Although pivotal to mentoring success, scant data on mentoring relationships
      continue to hamper the application of mentoring programs in nursing education. To
      address this gap and circumnavigate mentoring's context-specific nature, this
      narrative review analyzes the perspectives and opinions of nurse mentors and
      mentees. The aim is to identify common themes in their mentoring experiences to
      better nurture effective mentoring relationships and programs in nursing.

PMID- 28492414
TI  - Motivated Strategies for Learning in Accelerated Second-Degree Nursing Students.
AB  - Students in a second-degree accelerated BSN program experience a rigorous
      curriculum and fast-paced introduction to the nursing profession. This study
      examined the relationships among self-esteem, motivation, learning strategies,
      demographic characteristics, and academic achievement. The results indicated that
      all of the students had good self-esteem; some demographic characteristics
      influenced the type of motivation and learning strategies they endorsed but did
      not influence their current academic performance.

PMID- 28492415
TI  - Anticoagulation Control in Patients With Ventricular Assist Devices.
AB  - Anticoagulation control has been associated with risk of thromboembolism and
      hemorrhage. Herein, we explore the relationship between anticoagulation control
      achieved in left ventricular assist device (LVAD) patients and evaluate the
      association with risk of thromboembolism and hemorrhage. Patients (19 years old
      or older) with a continuous flow LVAD placed from 2006 to 2012. Percent time
      spent in target range (PTTR) for international normalized ratio (INR) was
      estimated with target range of 2.0-3.0. Proportion of time spent in target range
      was categorized into PTTR > 60%, PTTR >= 50 < 60%, and PTTR < 50%. The
      relationship between PTTR and thromboembolism and hemorrhage was assessed. One
      hundred fifteen participants contributed 624.5 months of follow-up time. Only 20%
      of patients achieved anticoagulation control (PTTR > 60% for INR range of 2-3).
      After adjusting for chronic kidney disease, history of diabetes, history of
      atrial fibrillation, and age at implant, compared with patients with PTTR < 50%,
      the relative risk of thromboembolism in patients with PTTR >= 60% (hazard ratio
      [HR]: 0.37; 95% confidence interval [CI]: 0.14-0.96; p = 0.042) was significantly
      lower, but not for patients with a PTTR of >= 50 < 60% (HR: 0.21; 95% CI: 0.02
      1.82; p = 0.16). The relative risk for hemorrhage was also significantly lower
      among patients with a PTTR >= 60% (HR: 0.45; 95% CI: 0.21-0.98; p = 0.045), but
      not among those with PTTR of >= 50 < 60% (HR: 0.47; 95% CI: 0.14-1.56; p = 0.22).
      This current study demonstrates that LVAD patients remain in the INR target range
      an average of 42.9% of the time. To our knowledge, this is the first report with
      regard to anticoagulation control as assessed by PTTR and its association with
      thromboembolism, hemorrhage, or death among patients with ventricular assist
      devices (VADs).

PMID- 28492416
TI  - Cannabinoid 1 receptor blockade in the dorsal hippocampus prevents the
      reinstatement but not acquisition of morphine-induced conditioned place
      preference in rats.
AB  - The cannabinoid 1 receptors (CB1Rs) signaling is strongly linked to conditioned
      rewarding effects of opiates. Learned associations between environmental contexts
      and discrete cues and drug use play an important role in the maintenance and/or
      relapse of morphine addiction. Although previous studies suggest that context
      dependent morphine treatment alters endocannabinoid signaling and synaptic
      plasticity in the hippocampus, the role of endocannabinoid in morphine
      conditioned place preference (CPP) and reinstatement remains unknown. In the
      present study, we found daily escalating doses of morphine induce significant CPP
      in rats. After the extinction of CPP, a priming dose of morphine was sufficient
      to reinstate morphine CPP and was associated with the elevated CB1R levels
      compared with saline control groups, suggesting upregulation of CB1R pathway in
      the hippocampus contribute to the reinstatement of morphine CPP. By using a
      pharmacological inhibitor of CB1R administered into the dorsal hippocampus, we
      showed that blockade of CB1R signaling did not alter the morphine CPP acquisition
      but inhibited the reinstatement of morphine CPP. In addition, no effects were
      induced upon CB1R blockade in the prefrontal cortex on reinstatement of morphine
      CPP. These studies reveal region-specific effects of hippocampal blockade of CB1R
      signaling pathway on the reinstatement of morphine CPP.

PMID- 28492417
TI  - Cognitive control in children with learning disabilities: neuromarker for
      deficient executive functions.
AB  - The neural underpinnings of learning disabilities (LD) are still not known.
      Recent discussions focus over whether domain-specific and/or domain-unspecific
      reasons might be responsible for LD either alone or in combination with each
      other. This study applied standard nonverbal Go-NoGo tasks (visual continuous
      performance test) to LD and healthy control children to examine whether they show
      deficient executive functions. During this Go-NoGo task, electroencephalogram was
      measured in addition to reaction times, hits, omissions, and commissions to the
      Go and NoGo stimuli. It was shown that children with LD reacted slower with
      variable responses to Go stimuli and made more omission errors in comparison with
      the healthy control children. The analysis of the event-related potential
      indicated that the deficient behavior in this task is associated with smaller -
      and in part nonexistent - P3d amplitudes. This neural activation indicates a
      different neural activation pattern during action inhibition in LD children. The
      neural networks involved in controlling action inhibition are mostly located in
      frontal brain areas, for which it has been shown that children with LD show
      neural activation deficiencies. This is possibly a consequence of a maturational
      delay of the frontal cortex.

PMID- 28492418
TI  - Clinical Feasibility of Free-Breathing Dynamic T1-Weighted Imaging With Gadoxetic
      Acid-Enhanced Liver Magnetic Resonance Imaging Using a Combination of Variable
      Density Sampling and Compressed Sensing.
AB  - OBJECTIVES: The purpose of the study was to investigate the clinical feasibility
      of free-breathing dynamic T1-weighted imaging (T1WI) using Cartesian sampling,
      compressed sensing, and iterative reconstruction in gadoxetic acid-enhanced liver
      magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study
      was approved by our institutional review board, and the requirement for informed
      consent was waived. A total of 51 patients at high risk of breath-holding failure
      underwent dynamic T1WI in a free-breathing manner using volumetric interpolated
      breath-hold (BH) examination with compressed sensing reconstruction (CS-VIBE) and
      hard gating. Timing, motion artifacts, and image quality were evaluated by 4
      radiologists on a 4-point scale. For patients with low image quality scores (<3)
      on the late arterial phase, respiratory motion-resolved (extradimension [XD])
      reconstruction was additionally performed and reviewed in the same manner. In
      addition, in 68.6% (35/51) patients who had previously undergone liver MRI, image
      quality and motion artifacts on dynamic phases using CS-VIBE were compared with
      previous BH-T1WIs. RESULTS: In all patients, adequate arterial-phase timing was
      obtained at least once. Overall image quality of free-breathing T1WI was 3.30 +/-
      0.59 on precontrast and 2.68 +/- 0.70, 2.93 +/- 0.65, and 3.30 +/- 0.49 on early
      arterial, late arterial, and portal venous phases, respectively. In 13 patients
      with lower than average image quality (<3) on the late arterial phase, motion
      resolved reconstructed T1WI (XD-reconstructed CS-VIBE) significantly reduced
      motion artifacts (P < 0.002-0.021) and improved image quality (P < 0.0001-0.002).
      In comparison with previous BH-T1WI, CS-VIBE with hard gating or XD
      reconstruction showed less motion artifacts and better image quality on
      precontrast, arterial, and portal venous phases (P < 0.0001-0.013). CONCLUSIONS:
      Volumetric interpolated breath-hold examination with compressed sensing has the
      potential to provide consistent, motion-corrected free-breathing dynamic T1WI for
      liver MRI in patients at high risk of breath-holding failure.

PMID- 28492420
TI  - Helminthic Therapy: A New Era in Immune-Mediated Diseases.

PMID- 28492419
TI  - Seroprevalence of antibodies and antigens against hepatitis A-E viruses in
      refugees and asylum seekers in Germany in 2015.
AB  - BACKGROUND: Migration because of miscellaneous political crises in countries in
      the Middle East and Africa is a global challenge for whole Europe from an
      economic, social, and public health view. There is an urgent need to generate
      comprehensive, evidence-based data to expedite further screening and vaccination
      strategies. METHODS: A total of 604 individuals ranging in age from 2 to 68 years
      who enrolled at a single reception center were tested for the prevalence of
      serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV,
      HDV, HEV), respectively. RESULTS: Anti-HAV antibody prevalence was 91.2 and 70.3%
      in children younger than 18 years of age. The prevalence of anti-HEV antibodies
      was 20.1% among the individuals. 3.0% were positive for hepatitis B surface
      antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of
      the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated
      against hepatitis B and had a protective anti-hepatitis B surface level of at
      least 10 mIU/ml. Significant differences in vaccination status were found between
      the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence
      interval=12.7-19.3%) versus African Region with 1/55 (1.8%; 95% confidence
      interval=0-5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7%
      HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals
      were HCV coinfected (n=3). CONCLUSION: The prevalence of refugees with previous
      exposure to hepatitis viruses was higher than that in the general German
      population, but lower than in other migrant populations in Germany. The
      vaccination status against hepatitis B was poor.

PMID- 28492421
TI  - Description of Malignancy Rates in Childhood- and Adult-Onset Systemic Lupus
      Erythematous by Proportional Meta-analysis.
AB  - OBJECTIVE: Describe malignancy rates in childhood onset and adult onset systemic
      lupus erythematous (SLE) by proportional meta-analysis. METHODS: Two reviewers
      screened data from PubMed (1966-2015), EMBASE (1980-2015), and LILACS (1982-2015)
      for SLE-associated malignancy. Proportional meta-analysis with a random-effects
      model and 95% confidence intervals (CIs) were calculated according to SLE onset
      age and mean follow-up time. Statistical difference was defined by 95% CI
      overlap. RESULTS: Overall the malignancy rate reported in 30 case series with
      96,578 subjects was 3.4% (95% CI, 0.0260-0.0442; I = 97.6%; P < 0.0001). The
      malignancy rate was 4.2% (95% CI, 0.0318-0.0531; I = 98%; P < 0.0001) in 25 adult
      onset SLE series, compared with 0.5% (95% CI, 0.0003-0.0154; I = 62.6%; P = 0.03)
      in 5 childhood-onset SLE series. Overall, in those with less than 5 years' follow
      up, the malignancy rate was 2.8% (95% CI, 0.013-0.047; I = 91%; P < 0.0001)
      compared with 3.6% (95% CI, 0.0226-0.0531; I = 98.3%; P < 0.0001) in those with
      more than 5 years' follow-up, which was not significant, with 95% CI overlap.
      CONCLUSIONS: The meta-analysis indicated lower malignancy rates in pediatric
      onset SLE compared with adult-onset SLE, but accrued data from childhood-onset
      SLE are still needed.

PMID- 28492422
TI  - Increasing Patient-Clinician Concordance About Medical Error Disclosure Through
      the Patient TIPS Model.
AB  - OBJECTIVE: To test whether an educational model involving patients and family
      members (P/F) in medical error disclosure training for interprofessional
      clinicians can narrow existing gaps between clinician and P/F views about
      disclosure. METHOD: Parallel presurveys/postsurveys using Likert scale questions
      for clinicians and P/F. RESULTS: Baseline surveys were completed by 91% (50/55)
      of clinicians who attended the workshops and 74% (65/88) of P/F from a hospital
      patient and family advisory council. P/F's baseline views about disclosure were
      significantly different from clinicians' in 70% (7/10) of the disclosure
      expectation items and 100% (3/3) of the disclosure vignette items. For example,
      compared with clinicians, P/F more strongly agreed that "patients want to know
      all the details of what happened" and more strongly disagreed that "patients find
      explanation(s) more confusing than helpful." In the medication error vignette,
      compared with clinicians, P/F more strongly agreed that the error should be
      disclosed and that the patient would want to know and more strongly disagreed
      that disclosure would do more harm than good (all P < 0.05). After the workshop,
      P/F and clinician views about information sharing, fallibility, truth telling,
      and threshold for disclosure showed greater concordance, with significant
      differences remaining in less than half of the expectation items and none of the
      vignette responses. DISCUSSION: Even with self-selecting clinicians,
      collaborative learning with P/F highlights important differences in patient and
      clinician baseline perspectives about medical error disclosure and brings patient
      and clinicians views closer together.

PMID- 28492423
TI  - A Survey of the Opinion and Experience of UK Dentists Part 3: An Evidence-Based
      Protocol of Surgical Risk Management Strategies in the Mandible.
AB  - BACKGROUND: Implant surgery in the mandible can cause serious complications that
      can be life threatening. The incidence and cause of iatrogenic trigeminal nerve
      injury (TNI) related to dental implant surgery was investigated in a survey of
      the opinion and experience of the UK dentists and reported by the authors in part
      1 of this series of articles. Part 2 reported on the risk assessment and
      management of implant-related inferior alveolar nerve (IAN), mental nerve (MN),
      and lingual nerve (LN) injuries. This article evaluates the significance of these
      findings and recommends an evidence-based protocol of risk management strategies
      to reduce the risk of TNI related to dental implant surgery. METHODS: A survey
      was distributed among 405 dentists attending an Association of Dental
      Implantology (ADI) congress, of which 187 completed the survey. RESULTS: In this
      study, the strategies to manage the risk of TNI included unilateral staging of
      implant placement (57%) and identification the MN when placing implants (43%).
      Twelve percent used drill stops when operating in the mandible. Nineteen dentists
      used steroids (eg, dexamethasone) routinely preoperatively and postoperatively.
      Twenty-six dentists used basic cone beam computed tomography minimally invasive
      techniques, and 70% encountered a large anterior loop of the IAN. Most dentists
      (76%) allowed a 2- to 4-mm safety zone radiologically above the IAN when placing
      implants, and over half of the responders (56%) used implants that were 10 mm in
      length. CONCLUSION: Given the elective nature of implant surgery, TNI should be
      fully avoidable. The evidence suggest that TNI can be minimized with meticulous
      attention to accurate assessment and surgical planning as well as carrying out
      the surgery with a high degree of precision. In part 3 of their series of
      articles, the authors presented an evidence-based protocol that comprises
      preoperative, intraoperative, and postoperative risk management strategies for
      dental implant surgical procedures in the mandible.

PMID- 28492424
TI  - A New Highly Hydrophilic Electrochemical Implant Titanium Surface: A Histological
      and Biomechanical In Vivo Study.
AB  - PURPOSE: The aim was to compare the osseointegration degree and secondary implant
      stability between implants with different surface treatments. MATERIALS AND
      METHODS: A novel electrochemical treatment was applied to modify the sandblasted
      and acid-etched surface (SLA) to obtain the new hydrophilic Feeling (FEL) surface
      presenting a highly soluble and homogenous film made of calcium and phosphorus
      nanocrystals. Twenty 3.8 * 10-mm dynamix implants (Cortex) were inserted in sheep
      iliac crests. Sheep were killed after 2 months. Bone-to-implant contact
      percentage (%BIC) and biomechanical parameters, such as implant stability
      quotient (ISQ) and value of actual micromotion (VAM), were evaluated for each
      implants. RESULTS: No implant failures were observed. Implants of test group
      showed %BIC value 30% higher in respect with control group (P = 0.001). No
      statistical differences were detected between the 2 groups in VAM and ISQ values.
      CONCLUSION: Both surface treatments were highly osteoconductive because they were
      able to significantly increase the bone density onto implant surface in respect
      with that in which they were inserted (D4 bone density). The hydrophilic FEL
      surface demonstrated an increase of about 216% in BIC in respect with host bone
      density and an additional 30% more in respect with SLA surface. Faster
      osseointegration process is desirable in case of early implant loading protocol.

PMID- 28492425
TI  - Identifying Patient and Provider-specific Gaps in Care Among Patients With
      Hepatitis B.
AB  - GOALS: To examine patient, provider, and health system barriers to clinical
      follow-up among US veterans with chronic hepatitis B virus (HBV). BACKGROUND:
      Studies have demonstrated deficiencies in clinical care and follow-up in HBV;
      however, patient, provider, and health-system barriers in non-Asian populations
      are understudied. STUDY: A retrospective cohort of 517 US veterans with chronic
      HBV at 3 diverse Veterans Affairs sites from 1999 to 2015. Laboratory testing and
      completion of clinical appointments were collected for 2 years following initial
      presentation. RESULTS: Among HBV patients, 36% had drug abuse, 41% alcohol
      misuse, and 45% had psychiatric disorders. Patients had an average of 4.4 primary
      care visits within 2 years of the index hepatitis B surface antigen positive
      result, 38% had psychiatry visits, 21% had a psychiatric hospitalization; 26% saw
      gastroenterology/hepatology specialists. Within 1 year of the index hepatitis B
      surface antigen positive result, 75% had alanine aminotransferase testing, 14%
      had HBV entered into the problem list, and 8% had serologic confirmation. In
      multivariable analyses, cirrhosis [odds ratio (OR)=3.42; 95% confidence interval
      (CI), 1.84-6.36] was associated with higher odds of appropriate laboratory
      testing, alcohol misuse (OR=0.45; 95% CI, 0.29-0.80) was associated lower odds.
      Cirrhosis (OR=2.03; 95% CI, 1.11-3.72) and >=2 primary care visits per year
      (OR=1.06; 95% CI, 1.01-1.11) were associated with higher odds of completing
      gastroenterology/hepatology consultation, whereas >=1 psychiatric hospitalization
      in 2 years was associated with lower odds (OR=0.53; 95% CI, 0.34-0.82).
      CONCLUSIONS: In a diverse cohort of veterans with high psychiatric comorbidity
      and substance abuse, important patient and provider factors influence appropriate
      follow-up care. Future studies should evaluate the impact of provider education
      and care coordination strategies in HBV.

PMID- 28492426
TI  - Trichotillomania in Attention-Deficit/Hyperactivity Disorder Under
      Methylphenidate Treatment.

PMID- 28492427
TI  - QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANALYSIS OF RETINAL DEGENERATIVE
      CHANGES IN DIABETIC MACULAR EDEMA AND NEOVASCULAR AGE-RELATED MACULAR
      DEGENERATION.
AB  - PURPOSE: To investigate the relationship of the pre-anti-vascular endothelial
      growth factor (VEGF) retinal tissue area (RTA) and optical density (ODRT) of the
      retinal optical slice portion located in the central subfield, and their ratio
      (RTA/ODRT), in the presence of diabetic macular edema or of inraretinal cystic
      fluid in neovascular age-related macular degeneration, to central retinal
      thickness and best-corrected visual acuity after anti-VEGF treatment with ME
      resolution. METHODS: The optical coherence tomography images and medical records
      of 33 patients (41 eyes) with neovascular age-related macular degeneration, 15
      (21 eyes) with diabetic macular edema and 9 healthy individuals (15 eyes) were
      retrospectively analyzed. RTA, ODRT, and RTA/ODRT were calculated on pre-anti
      VEGF B-scan images. Spearman rank correlation was used to assess the relationship
      of central retinal thickness and best-corrected visual acuity after anti-VEGF
      treatment with the variables under study. RESULTS: Pre-anti-VEGF RTA was
      positively correlated with post-anti-VEGF central retinal thickness (rho = 0.76;
      P < 0.001) and best-corrected visual acuity (rho = 0.67; P < 0.001), whereas pre
      anti-VEGF ODRT was moderately negatively correlated (rho = -0.26; P = 0.049 and
      rho = -0.48; P = 0.001, respectively) and pre-anti-VEGF RTA/ODRT ratio was
      strongly positively correlated (rho = 0.75; P < 0.001 and rho = 0.85; P < 0.001,
      respectively). The area under curve for RTA/ODRT ratio was 0.93 (P < 0.001), and
      the cut-off value for post-anti-VEGF LogMAR best-corrected visual acuity of 0.4
      (20/50 Snellen equivalent) or worse was 1,406.7 MUm/U (sensitivity: 0.94;
      specificity: 0.78). CONCLUSION: Both RTA and ODRT, or, preferably, RTA/ODRT ratio
      alone can be used as predictors of functional and anatomic outcomes in patients
      with diabetic macular edema or neovascular age-related macular degeneration
      treated with anti-VEGF therapy.

PMID- 28492428
TI  - A PROSPECTIVE, RANDOMIZED TRIAL COMPARING PLAIN GUT TO POLYGLACTIN 910 (VICRYL)
      SUTURES FOR SCLEROTOMY CLOSURE AFTER 23-GAUGE PARS PLANA VITRECTOMY.
AB  - PURPOSE: To report a prospective, randomized comparative study assessing clinical
      outcomes of plain gut versus polyglactin 910 (PG910) sutures for sclerotomy
      closure after 23-gauge pars plana vitrectomy. METHODS: A single-masked,
      randomized, prospective study was undertaken with 49 eyes of 49 patients
      undergoing 23-gauge pars plana vitrectomy randomized to sclerotomy closure with
      either plain gut suture, PG910 (Vicryl) suture or a combination of the two.
      Assessment was based on both a postoperative pain scale and a standardized
      assessment of scleral inflammation at each suture site. RESULTS: No wound leakage
      was noted postoperatively in any patient. Across all groups, scleral inflammation
      was significantly higher at the PG910 suture sites compared with the plain gut
      suture sites at both the 1-week (P = 0.04) and 1-month postoperative visits (P <
      0.001). Patients with PG910 sutures reported greater pain at the 1-month
      postoperative visit than those with plain gut sutures (P = 0.018). CONCLUSION:
      This prospective study suggests improved tolerability and reduced inflammation
      using plain gut suture compared with an 8-0 PG910 suture to close 23-gauge
      sclerotomies.

PMID- 28492429
TI  - THREE-DIMENSIONAL ANALYSIS OF SUBMACULAR PERFORATING SCLERAL VESSELS BY ENHANCED
      DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To analyze submacular perforating scleral vessels (PSVs) using enhanced
      depth imaging spectral domain optical coherence tomography (EDI-SDOCT). METHODS:
      Twenty-two eyes of 11 healthy women were included in this retrospective study.
      Central EDI-SDOCT scans (3 * 4.5 * 1.9 mm, 13.5 mm scan area) were acquired and
      postprocessed by denoising, manual sclera segmentation, and PSV investigated by
      five graders. RESULTS: Mean age was 22.4 +/- 6.2 years. Mean refractive error was
      -0.44 +/- 0.8 diopters. Mean axial length was 23.08 +/- 0.63 mm. The coefficient
      of agreement for grading was good. Mean number of submacular PSVs was 0.33 +/-
      0.2 per mm (range from 0 to 9 per eye). Subfield analysis showed 0.2 +/- 0.5
      (range 0-2) and 2.1 +/- 1.8 (range 0-7) vessels, respectively, for central 1-mm
      diameter and 3-mm diameter. Quadrant analysis showed 0.7 +/- 0.9, 0.5 +/- 0.9,
      0.3 +/- 0.6, and 0.4 +/- 0.6 vessels, respectively for superior, inferior, nasal,
      and temporal quadrants. Total number of PSV showed no significant side difference
      (median difference 0.5, confidence interval -3.0 to 3.0, P = 0.94) or an
      influence of axial length (P = 0.16). CONCLUSION: This is the first description
      of three-dimensional EDI-SDOCT visualization of submacular PSV in healthy eyes.
      This method allows for in vivo imaging of a critical component of outer retinal
      perfusion at the posterior pole.

PMID- 28492430
TI  - SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN ENDOGENOUS CANDIDA
      ENDOPHTHALMITIS AND THEIR CLINICAL RELEVANCE.
AB  - PURPOSE: To describe vitreal, retinal, and choroidal features of eyes affected by
      Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical
      coherence tomography (SD-OCT) and to evaluate their clinical impact. METHODS:
      Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and
      uveitis tertiary referral centers were retrospectively evaluated. Spectral domain
      optical coherence tomography images were analyzed to evaluate the structural
      changes occurring in the vitreous, the retina, and the choroid in areas involved
      by ECE. Baseline and final best-corrected visual acuity were correlated with SD
      OCT findings. RESULTS: Fifteen eyes from nine patients were enrolled. Vitreous
      involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15
      eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying
      retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes
      with vitreous involvement. Two patterns of retinal and choroidal findings were
      identified: the first (six eyes) confined within the inner retinal layers
      (Intraretinal Pattern), the second (nine eyes) involving both retina (full
      thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed
      both patterns. None of the eyes, regardless the pattern, showed choroidal
      thickening. Baseline best-corrected visual acuity was not associated with OCT
      pattern (P = 0.09). On the contrary, final best-corrected visual acuity was
      significantly higher in patients showing Intraretinal Pattern (~20/25, 0.06 +/-
      0.08 LogMAR) than in subjects with Chorioretinal Pattern (~20/50, 0.44 +/- 0.30
      LogMAR) (P = 0.01). CONCLUSION: Endogenous candida endophthalmitis showed
      peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement
      influencing the final best-corrected visual acuity were identified. Spectral
      domain optical coherence tomography could be useful in the diagnosis, management,
      and outcome prediction in ECE.

PMID- 28492431
TI  - EXPERIENCE USING A 3D HEAD-MOUNTED DISPLAY SYSTEM IN OPHTHALMIC SURGERY.

PMID- 28492432
TI  - VASCULAR DISTORTION AND DRAGGING RELATED TO APPARENT TISSUE CONTRACTION IN
      MACULAR TELANGIECTASIS TYPE 2.
AB  - PURPOSE: To examine the alterations in retinal vascular morphology over an
      extended follow-up in eyes with macular telangiectasis Type 2 (MacTel2). METHODS:
      Eyes with high-quality digital photographs were evaluated. The geometric
      distortion in baseline images required to emulate the follow-up images was
      determined and vectors were made that represented the direction and magnitude of
      changes, to create a warp field. Optical coherence tomography and optical
      coherence tomography angiography evaluation of the retina was performed. RESULTS:
      There were 7 eyes of 4 patients, who had a mean age of 70.25 years, which were
      followed for a mean of 8.8 years. The eyes showed increasing grayish
      opacification in the temporal macula with straightening and displacement of the
      macular vessels, even those in the nasal macula. The warp field vectors pointed
      to the temporal juxtafoveal macula. There was never any cavitation at the
      epicenter of the retinal distortion in any patient, although cavitations were
      found around this area. Optical coherence tomography imaging showed a
      circumscribed region of hyperreflectivity in the temporal macula. Optical
      coherence tomography angiography showed a deep angular condensed network of
      vessels within the hyperreflective region. One eye showed marked atrophic changes
      including full-thickness macular hole formation, but no increase in graying of
      the retina, loss of retinal laminations, pigmentary infiltration, or alteration
      in the retinal vessels. CONCLUSION: Tissue contraction with retinal vascular
      displacement and contortion seem to be integral aspects of disease manifestation
      in MacTel2. The induced vascular changes may lead to secondary effects that
      increase morbidity in this disease.

PMID- 28492433
TI  - COMBINED PARS PLANA VITRECTOMY AND SCLERAL FIXATION OF AN INTRAOCULAR LENS USING
      GORE-TEX SUTURE: One-Year Outcomes.
AB  - PURPOSE: To report the 1-year clinical outcomes of combined pars plana vitrectomy
      and ab externo scleral fixation of an intraocular lens using Gore-Tex suture.
      METHODS: Retrospective, interventional case series. Outcome measures were change
      in visual acuity and occurrence of intraoperative and postoperative complications
      with minimum follow-up of 1 year. RESULTS: Eighty-four eyes of 83 patients were
      identified. The mean best available visual acuity improved from 20/782
      preoperatively to 20/65 postoperatively (P < 0.001). The mean follow-up was 598
      +/- 183 days (median 533 days, range 365-1,323 days). There were no
      intraoperative complications noted. A Bausch & Lomb Akreos AO60 intraocular lens
      was implanted in 77 eyes and an Alcon CZ70BD in 7 eyes. Postoperative
      complications included transient vitreous hemorrhage in six eyes (7.1%), cystoid
      macular edema in four eyes (4.8%), ocular hypertension in three eyes (3.6%),
      hyphema in two eyes (2.4%), and transient corneal edema in two eyes (2.4%). There
      were no cases of postoperative endophthalmitis, suture erosion/breakage,
      hypotony, retinal detachment, suprachoroidal hemorrhage, choroidal detachment,
      uveitis-glaucoma-hyphema syndrome, or persistent postoperative inflammation
      during the follow-up period. CONCLUSION: Combined pars plana vitrectomy and ab
      externo scleral fixation of an intraocular lens with Gore-Tex suture was well
      tolerated at a minimum of 1-year follow-up. No suture-related complications were
      encountered.

PMID- 28492434
TI  - LONGITUDINAL CHANGE OF OUTER NUCLEAR LAYER AFTER RETINAL PIGMENT EPITHELIAL TEAR
      SECONDARY TO AGE-RELATED MACULAR DEGENERATION.
AB  - PURPOSE: To investigate longitudinal changes of outer nuclear layer (ONL)
      thickness in patients with retinal pigment epithelium tears secondary to
      neovascular age-related macular degeneration. METHODS: This is an institutional
      retrospective interventional case series. Twenty-six eyes of 22 patients with
      retinal pigment epithelium tears identified between April 2009 and March 2015.
      The patients underwent intravitreal injection of anti-vascular endothelial growth
      factor agents as needed. Volume scans of optical coherence tomography at first
      diagnosis of tear (baseline) and after 12 months were analyzed. Outer nuclear
      layer was segmented, and average ONL thickness inside the tear area, at the
      border of the tear, and in areas outside the tear was measured. Change of ONL
      thickness. We also explored several factors for their association with ONL
      thinning including tear area, number of treatments, and the duration with
      persistent subretinal fluid. RESULTS: Thinning of ONL was found in all the
      investigated areas (P < 0.01, respectively). Among the investigated factors,
      larger tear area was associated with greater ONL thinning outside the tear area
      (standardized beta = -0.37, P = 0.030), and younger age was associated with
      greater ONL thinning inside the tear area (standardized beta = 0.37, P = 0.041).
      CONCLUSION: After an retinal pigment epithelium tear, thinning of ONL occurs in
      the area devoid of retinal pigment epithelium and also in adjacent areas. Few
      factors were predictive for the degree of ONL thinning. These results provide new
      insight in disease progression of this particular neovascular age-related macular
      degeneration subphenotype.

PMID- 28492435
TI  - CLINICAL FINDINGS OF EYES WITH MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN
      OCCLUSION REFRACTORY TO RANIBIZUMAB.
AB  - PURPOSE: To determine the relationship between the clinical findings and the
      response to ranibizumab therapy in eyes with macular edema associated with branch
      retinal vein occlusion. METHODS: We reviewed the medical records of 68 patients
      with macular edema associated with a branch retinal vein occlusion. The patients
      were placed in the refractory group if the central foveal thickness remained more
      than 250 MUm throughout the 6-month study period despite the ranibizumab therapy;
      otherwise, they were placed in the responsive group. RESULTS: Sixty (88.2%) of 68
      eyes were placed in the responsive group and the other 8 eyes (11.8%) were placed
      in the refractory group. At the pretreatment examination, fluorescein angiography
      showed extensive leakage from occluded vessels in 52 (86.7%) of the 60 eyes in
      the responsive group and focal leakages from microaneurysms or dilated
      capillaries in the other 8 eyes (13.3%). In the refractory group, 7 (87.5%) of 8
      eyes had only focal leakage and 1 eye (12.5%) had extensive leakage (P < 0.0001).
      The mean initial subfoveal choroidal thickness in the eyes with branch retinal
      vein occlusion in the responsive group was significantly thicker than that in the
      fellow eyes (278.0 +/- 90.5 MUm, 249.9 +/- 94.4 MUm; P < 0.0001). On the other
      hand, the mean initial subfoveal choroidal thickness in the refractory group was
      not significantly different from that of the fellow eyes (P = 0.4002).
      CONCLUSION: The dye leakage pattern in the fluorescein angiography images and
      choroidal thickness may be associated with response to ranibizumab therapy.

PMID- 28492436
TI  - Continuous Regional Anesthesia and Inpatient Rehabilitation for Pediatric Complex
      Regional Pain Syndrome.
AB  - BACKGROUND: Evidence supports treatment of pediatric complex regional pain
      syndromes (CRPS) with physical and occupational therapy and cognitive-behavioral
      therapy. Some patients have persistent pain and/or limb dysfunction despite these
      treatments. We performed a retrospective study of pediatric patients with CRPS
      treated by continuous epidural or peripheral perineural local anesthetic
      infusions along with inpatient rehabilitation at Boston Children's Hospital.
      METHODS: After approval from the institutional review board, electronic medical
      records were reviewed for patients treated between September 2003 and September
      2014. Primary outcomes were pain and functional scores. Data were collected at
      the first encounter, at follow-up visits between 4 months before and after
      admission, and daily while inpatient. Changes over time were assessed using
      Wilcoxon tests with Dunn corrections. Clinical significance of benefit or harm
      was assessed by the method of Jacobson and Truax. Response predictors were
      analyzed using linear mixed models and exploratory logarithmic regression
      analyses. RESULTS: Pain, function, and disability scores improved during
      hospitalization and in follow-up over a 4-month period. Seventy percent of
      patients achieved clinically significant benefit (56% for pain reduction and 40%
      increased functionality, respectively). Univariate and adjusted predictors of
      favorable outcome included preadmission resting Numeric Pain Rating Scale score
      of less than 6 (odds ratio, 5.0; P = 0.0164 and subsequent attendance at the
      Pediatric Pain Rehabilitation Center at Boston Children's Hospital (odds ratio,
      5.0; P = 0.0206). Mean pain scores greater than 3 during the regional anesthesia
      infusion predicted less favorable outcome. CONCLUSIONS: Continuous regional
      anesthesia may be an option to facilitate intensive rehabilitation for selected
      pediatric patients with CRPS. Further research should help clarify the role of
      regional anesthesia in a comprehensive management program.

PMID- 28492437
TI  - Continuous Intrathecal Infusion of Cannabinoid Receptor Agonists Attenuates Nerve
      Ligation-Induced Pain in Rats.
AB  - BACKGROUND AND OBJECTIVES: Cannabinoid receptors (CB1R/CB2R) are known to play
      important roles in pain transmission. In this study, we investigated the effects
      of continuous intrathecal infusion of CB1/2R agonists in the L5/6 spinal nerve
      ligation pain model. METHODS: Under isoflurane anesthesia, rats received nerve
      ligation and intrathecal catheter connected to an infusion pump. After surgery,
      saline (1 MUL/h), CB1/2R agonist WIN55,212-2, CB1R agonist ACEA, or CB2R agonist
      AM1241 (1 MUmol/h) was given intrathecally for 7 days. The mechanical and thermal
      sensitivities of rat hindpaw were determined by von Frey hair and radiant heat
      tests. The expression of CB1/2R and protein levels of CB1/2R, Iba1, glial
      fibrillary acidic protein, and tumor necrosis factor alpha were examined by
      immunofluorescence study and Western blotting. RESULTS: On postligation day 7,
      rats that received WIN55,212-2, ACEA or AM1241 had significantly higher mean
      withdrawal thresholds (6.8, 8.4, and 10.2 g) and latencies (6.3, 7.3, and 9.1
      seconds) than did saline-treated rats (1.7 g, 2.2 seconds). Cannabinoid receptors
      were expressed not only in IB4 (isolectin B4) and CGRP (calcitonin gene-related
      peptide) dorsal root ganglion neurons, their central terminals, and peripheral
      axons, but also in neurons, microglia, and astrocytes in spinal cord. Cannabinoid
      receptor agonists enhanced nerve ligation-induced up-regulation of cannabinoid
      receptor in spinal cord and dorsal root ganglion. Treatment with WIN55,212-2 or
      AM1241, but not ACEA, markedly reduced nerve ligation-induced up-regulation of
      Iba1, glial fibrillary acidic protein, and tumor necrosis factor alpha in spinal
      cord. CONCLUSIONS: Continuous intrathecal infusion of CB1/2R agonists elicits
      antinociception in the pain model. The mechanisms might involve their actions on
      neurons and glial cells. CB2R, but not CB1R, seems to play an important role in
      the regulation of nerve injury-induced neuroinflammation.

PMID- 28492438
TI  - Advancing Safety in Intrathecal Analgesia: A Novel Web-Based Pharmacologic
      Requisition Platform and Data Repository for Intrathecal Drug Delivery Devices.

PMID- 28492439
TI  - Retrobulbar Block in Pediatric Vitreoretinal Surgery Eliminates the Need for
      Intraoperative Fentanyl and Postoperative Analgesia: A Randomized Controlled
      Study.
AB  - BACKGROUND AND OBJECTIVES: Pediatric ophthalmologic surgery is traditionally
      accomplished by general anesthesia with opioids, but respiratory depression
      remains a major concern. Our study compared the efficacy of retrobulbar block
      with systemic fentanyl on pain, hemodynamic, and stress response in pediatric
      vitreoretinal surgery. METHODS: A prospective double-blind, randomized controlled
      study was performed comparing retrobulbar block with intravenously administered
      fentanyl in 28 children aged 1 to 6 years undergoing vitreoretinal surgery. After
      general anesthesia was induced, retrobulbar block with 0.5% ropivacaine was
      accomplished in group RB (general anesthesia plus retrobulbar block) (n = 13),
      and normal saline was injected into retrobulbar space in group F (general
      anesthesia alone) (n = 15). Fentanyl 0.5 MUg/kg was administered when signs of
      inadequate anesthesia were observed. RESULTS: Respiratory depression (defined as
      a persistent respiratory rate <10 breaths/min or persistent oxygen desaturation
      <92%) was observed in 5 of 15 patients in group F after laryngeal mask airway was
      removed in the operating room, compared with none in group RB. All children in
      group F consumed intraoperative fentanyl rescue (average intraoperative fentanyl
      consumption, 1.3 +/- 0.3 MUg/kg) compared with none in group RB. Pain scores
      assessed with Faces, Legs, Activity, Cry and Consolability were significantly
      lower in group RB than in group F (1 [0, 3.5] vs 5 [3, 7], P = 0.003) immediately
      after laryngeal mask airway removal. Heart rate in group RB was significantly
      lower than that in group F before anesthesia induction, at the beginning and end
      of surgery, respectively. Mean blood pressure in group RB was significantly lower
      than that in group F at the beginning of surgery. Postoperative tumor necrosis
      factor alpha concentration in group RB was significantly lower than that in group
      F. CONCLUSIONS: Retrobulbar block is safe and effective as an alternative to
      systemic fentanyl and could provide better pain management, hemodynamic
      suppression, and stress response suppression in pediatric vitreoretinal surgery.

PMID- 28492440
TI  - Diskitis, Osteomyelitis, Spinal Epidural Abscess, Meningitis, and Endocarditis
      Following Sacroiliac Joint Injection for the Treatment of Low-Back Pain in a
      Patient on Therapy for Hepatitis C Virus.
AB  - OBJECTIVE: Sacroiliac joint injections are frequently performed procedures in the
      management of acute and chronic low-back pain, including patients with various
      immunocompromised states. Infectious complications following these procedures
      along with other spinal injections are rarely reported, but the true incidence is
      unknown. The purpose of this report is to highlight the devastating neurologic
      sequela that can occur, and to discuss potential future management strategies.
      CASE REPORT: We present a patient who developed diskitis, osteomyelitis, spinal
      epidural abscess, meningitis, and endocarditis from Staphylococcus aureus, all of
      which developed shortly after a sacroiliac joint injection. The patient was on
      treatment for hepatitis C virus, and the resulting immunocompromised state likely
      contributed to the outcome. CONCLUSIONS: Immunocompromised patients should be
      identified prior to treatment, and the small possibility of devastating
      complications should be thoughtfully weighed against the potential benefit of the
      procedure. Conservative management should be maximized initially, and if a
      procedure is done, strict asepsis must be maintained. Prophylaxis for S. aureus
      should be considered for immunocompromised patients undergoing interventional
      spine procedures.

PMID- 28492441
TI  - Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American
      Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines.
AB  - Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA)
      anticoagulation guidelines recommend that before the performance of a neuraxial
      procedure a minimum of 24 hours should elapse following a treatment dose of
      enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have
      since their inception also consistently recommended against the routine use of
      anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in
      our clinical practice that anti-Xa levels were frequently still elevated despite
      patients meeting the time-based recommendation for treatment dose enoxaparin. To
      further investigate the possibility that residual anticoagulant activity may
      persist longer than 24 hours after a treatment dose of enoxaparin, we assessed
      anti-Xa level activity in patients presenting for elective surgery. Despite
      nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was
      drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19
      patients. While 10 patients had an anti-Xa level within the peak prophylactic
      range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak
      therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant
      anticoagulant activity may persist longer than previously appreciated after the
      last treatment dose of enoxaparin and that the current time-based ASRA
      recommendation may not be conservative enough. Further research is needed to
      delineate the level of anti-Xa activity below which it is likely safe to proceed
      with a neuraxial procedure, but it may be time to reconsider the utility of anti
      Xa level monitoring when it is available.

PMID- 28492442
TI  - Neuroendovascular Intervention: Evolving at the Intersection of Neurosurgery and
      Neuro-Ophthalmology.

PMID- 28492443
TI  - Intracranial Displacement of the Eye After Blunt Trauma: Retraction.

PMID- 28492444
TI  - Neuro-Ophthalmology: Transitioning From Old to New Models of Health Care
      Delivery.
AB  - In contradiction to fundamental laws of supply and demand, 2 decades of payment
      policies have led to some medical specialties experiencing declines in both
      manpower and reimbursement. This paradox has resulted in increasingly long wait
      times to see some specialists, some specialties becoming less attractive to
      potential trainees, and a dearth of new trainees entering these fields. Evolving
      models of health care delivery hold the promise of increasing patient access to
      most providers and may diminish costs and improve outcomes for most
      patients/conditions. However, patients who need care in understaffed fields may,
      in the future, be unable to quickly access a specialist with the requisite
      expertise. Impeding the sickest and most complex patients from seeing physicians
      with appropriate expertise may lead to increased costs and deleterious outcomes
      consequences contrary to the goals of health care reform. To ensure appropriate
      access for these patients requires 2 conditions: 1. Compensation models that do
      not discourage trainees from pursuing nonprocedural specialties, and 2. A care
      delivery model that expediently identifies and routes these patients to the
      appropriate specialist.

PMID- 28492445
TI  - Clomiphene Citrate Associated With Palinopsia.

PMID- 28492446
TI  - Five Community-wide Approaches to Physical Activity Promotion: A Cluster Analysis
      of These Activities in Local Health Jurisdictions in 6 States.
AB  - OBJECTIVE: Local health departments (LHDs) have essential roles to play in
      ensuring the promotion of physical activity (PA) in their communities in order to
      reduce obesity. Little research exists, however, regarding the existence of these
      PA interventions across communities and how these interventions may impact
      community health. DESIGN: In this exploratory study, we used cluster analysis to
      identify the structure of co-occurring PA interventions, followed by regression
      analysis to quantify the association between the patterns of PA interventions and
      prevalence of PA and obesity at a population level. SETTING: Our study setting
      included local health jurisdictions in Colorado, Florida, Minnesota, New Jersey,
      Tennessee, and Washington. PARTICIPANTS: Participating jurisdictions were those
      218 local health jurisdictions (mostly counties) from which LHD leaders had
      provided data in 2013 for the Multi-Network Practice and Outcome Variation
      Examination Study. MAIN OUTCOME MEASURES: We obtained unique public health
      activities data on PA interventions conducted in 2012 from 218 LHDs in 6
      participating states. We categorized jurisdictions using cluster analysis, based
      on PA intervention approaches indicated by LHD leaders as available in their
      communities and then examined associations between categories and prevalence of
      obesity and of residents engaged in PA. RESULTS: We identified 5 distinct PA
      intervention categories representing community-wide approaches-Comprehensive
      Approach, Built Environment, Personal Health, School-Based Interventions, and No
      Apparent Activities. Prevalence rates of obesity and PA among jurisdictions in
      the intervention clusters were significantly different from jurisdictions with No
      Apparent Activities, with more population-level approaches most significantly
      related to beneficial outcomes. CONCLUSION: Our findings suggest the importance
      of standardized public health services data for generating evidence regarding
      health-related outcomes. The intervention categories we identified appear to
      reflect broad, local community-wide prevention approaches and demonstrated that
      population-level PA interventions can be testable and may have particularly
      beneficial relationships to community health. Widespread adoption of such
      standardized data depicting local public health prevention activity could support
      monitoring practice change, performance improvement, comparisons across
      communities that could reduce unnecessary variation, and the generation of
      evidence for public health practice and policy-making.

PMID- 28492447
TI  - The Yellow Fever Vaccine Misadventure of 1942.
AB  - In 1942, a hepatitis B outbreak occurred in the US Army after vaccination with
      contaminated lots of 17D yellow fever vaccine; long-term sequelae were
      surprisingly limited, and retrospective studies of carrier rates, cirrhosis, and
      hepatocellular carcinoma were found to be minimal. Later studies identified the
      contaminant as hepatitis B virus (HBV) in the human serum component of the
      vaccine. Other than 2 follow-up studies of long-term sequelae and reports within
      US Military archives, the event has never been fully elucidated in its proper
      historical context in the medical literature available through MEDLINE (PubMed).
      The outbreak resulted in nearly 50 000 clinical cases, including 29 000 cases of
      overt jaundice. More than 300 000 troops may have been infected with HBV. The
      decision to immunize troops received criticism, but the decision may have been
      reasonable, given the exigencies of an impending war and the possibility that
      yellow fever could spread to future theaters of war. The epidemic was the largest
      and most well-documented vaccine-related epidemic in history. Today, independent
      of war, globalization has actually increased the likelihood of yellow fever
      importations to vulnerable areas of the world.

PMID- 28492448
TI  - Drivers and Barriers for Adopting Accreditation at Local Health Departments for
      Their Performance Improvement Effort.
AB  - CONTEXT: A national system of voluntary public health accreditation for state,
      local, and tribal health departments (local health departments [LHDs]) is part of
      a movement that aims to improve public health performance with ultimate impact on
      population health outcomes. Indiana is a good setting for the study of LHD
      accreditation adoption because several LHDs reported de-adopting accreditation in
      a recent statewide survey and because 71% of Indiana counties serve populations
      of 50 000 or less. DESIGN: A systematic method of analyzing qualitative data
      based on the Performance Improvement Model framework to expand our understanding
      of de-adoption of public health accreditation. SETTING/PARTICIPANTS: In 2015, we
      conducted a key informant interview study of the 3 LHDs that decided to delay
      their engagement in the accreditation based on findings from an Indiana survey on
      LHD accreditation adoption. The study is an exploration of LHD accreditation de
      adoption and of the contributions made to its understanding by the Performance
      Improvement Model. RESULT: The study found that top management team members are
      those who champion accreditation adoption, and that organizational structure and
      culture facilitate the staff's embracing of the change. The Performance
      Improvement Model was found to enhance the elucidation of the inner domain
      elements of Consolidated Framework for Implementation Research in the context of
      de-adoption of public health accreditation. CONCLUSION: Governing entities'
      policies and priorities appear to mediate whether the LHDs are able to continue
      accreditation pursuit. Lacking any of these driving forces appears to be
      associated with decisions to de-adoption of accreditation. Further work is
      necessary to discern specific elements mediating decisions to pursue
      accreditation. This study demonstrates the added knowledge of Performance
      Improvement Model (PIM) to the CFIR framework. A large scale study is called to
      further clarify and discern supports of specific to the needs of individual LHDs
      for their performance improvement effort.

PMID- 28492450
TI  - The Potential Role for Health Impact Assessments in Nonprofit Hospital Community
      Benefit Activities.

PMID- 28492451
TI  - Program-Led Program-Science: The Public Health Impact of the CDC Category C
      Health Department Model for HIV Prevention.

PMID- 28492449
TI  - Measuring Subcounty Differences in Population Health Using Hospital and Census
      Derived Data Sets: The Missouri ZIP Health Rankings Project.
AB  - CONTEXT: Measures of population health at the subcounty level are needed to
      identify areas for focused interventions and to support local health improvement
      activities. OBJECTIVE: To extend the County Health Rankings population health
      measurement model to the ZIP code level using widely available hospital and
      census-derived data sources. DESIGN: Retrospective administrative data study.
      SETTING: Missouri. POPULATION: Missouri FY 2012-2014 hospital inpatient,
      outpatient, and emergency department discharge encounters (N = 36 176 377) and
      2015 Nielsen data. MAIN OUTCOME MEASURES: ZIP code-level health factors and
      health outcomes indices. RESULTS: Statistically significant measures of
      association were observed between the ZIP code-level population health indices
      and published County Health Rankings indices. Variation within counties was
      observed in both urban and rural areas. Substantial variation of the derived
      measures was observed at the ZIP code level with 20 (17.4%) Missouri counties
      having ZIP codes in both the top and bottom quintiles of health factors and
      health outcomes. Thirty of the 46 (65.2%) counties in the top 2 county quintiles
      had ZIP codes in the bottom 2 quintiles. CONCLUSIONS: This proof-of-concept
      analysis suggests that readily available hospital and census-derived data can be
      used to create measures of population health at the subcounty level. These widely
      available data sources could be used to identify areas of potential need within
      counties, engage community stakeholders, and target interventions.

PMID- 28492453
TI  - Late Life.

PMID- 28492452
TI  - The Changing Landscape of HIV Prevention in the United States: Health Department
      Experiences and Local Adaptations in Response to the National HIV/AIDS Strategy
      and High-Impact Prevention Approach.
AB  - OBJECTIVE: HIV prevention has changed substantially in recent years due to
      changes in national priorities, biomedical advances, and health care reform.
      Starting in 2010, motivated by the National HIV/AIDS Strategy (NHAS) and the
      Centers for Disease Control and Prevention's (CDC's) High-Impact Prevention
      (HIP), health departments realigned resources so that cost-effective, evidence
      based interventions were targeted to groups at risk in areas most affected by
      HIV. This analysis describes how health departments in diverse settings were
      affected by NHAS and HIP. METHODS: We conducted interviews and a consultation
      with health departments from 16 jurisdictions and interviewed CDC project
      officers who monitored programs in 5 of the jurisdictions. Participants were
      asked to describe changes since NHAS and HIP and how they adapted. We used
      inductive qualitative analysis to identify themes of change. RESULTS: Health
      departments improved their HIV prevention practices in different ways. They
      aligned jurisdictional plans with NHAS and HIP goals, increased local data use to
      monitor program performance, streamlined services, and strengthened partnerships
      to increase service delivery to persons at highest risk for
      infection/transmission. They shifted efforts to focus more on the needs of people
      with diagnosed HIV infection, increased HIV testing and routine HIV screening in
      clinical settings, raised provider and community awareness about preexposure
      prophylaxis, and used nontraditional strategies to successfully engage out-of
      care people with diagnosed HIV infection. However, staff-, provider-, and data
      related barriers that could slow scale-up of priority programs were consistently
      reported by participants, potentially impeding the ability to meet national
      goals. CONCLUSION: Findings suggest progress toward NHAS and HIP goals has been
      made in some jurisdictions but highlight the need to monitor prevention programs
      in different contexts to identify areas for improvement and increase the
      likelihood of national success. Health departments and federal funders alike can
      benefit from the routine sharing of successes and challenges associated with
      local policy implementation, considering effects on the overall portfolio of
      programs.

PMID- 28492454
TI  - Use of Lithium in Severe Acute Manic Episodes: Retrospective Prescription
      Practice From a Tertiary Inpatient Unit.
AB  - OBJECTIVE: A retrospective chart review was performed to investigate the common
      preferences of clinicians for the pharmacological treatment of acute manic
      episodes, with particular regard to lithium use, and to assess the adherence of
      clinical practice to established guidelines. METHODS: Cases of manic episodes in
      patients admitted to Bakirkoy Mazhar Osman Mental Health and Neurological
      Diseases Education and Research Hospital were retrospectively reviewed. Length of
      stay, medication data, serum levels, and adverse effects were evaluated for
      patients who received lithium therapy (N=98). RESULTS: On the first day of
      lithium treatment, 81 patients received 900 to 1200 mg of lithium. In total, 44
      patients were discharged with the same dose as that given on the first day of
      treatment. With the exception of 1 patient, the dose was increased by 300 to 600
      mg in the remaining patients within the first 10 days on the basis of serum drug
      concentrations. The mean serum concentrations of lithium in the first week were
      0.67+/-0.17 mEq/L in patients with no dose increase, and 0.51+/-0.15 mEq/L in
      patients who did receive a dose increase. In total, 94 patients received at least
      1 antipsychotic medication in addition to lithium. CONCLUSIONS: Clinicians
      attempted to maintain serum lithium levels above 0.60 mEq/L at the time of acute
      treatment initiation, consistent with established guidelines. Clinical practice
      in large inpatient settings may force clinicians to use lithium in combination
      with antipsychotics for the treatment of acute mania; the delayed action of
      lithium and the need for rapid stabilization may drive these practices.

PMID- 28492455
TI  - Reevaluating Antidepressant Selection in Patients With Bruxism and
      Temporomandibular Joint Disorder.
AB  - Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to
      several conditions affecting the temporomandibular joint of the jaw and the
      muscles of mastication. As with most pain disorders, a high prevalence of
      depression and anxiety is associated with TMD. Research has shown that selective
      serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major
      depressive disorder, may not be suitable for TMD patients because SSRIs can
      induce teeth-grinding, otherwise known as bruxism. This is problematic because
      bruxism is believed to further exacerbate TMD. Therefore, the purpose of this
      literature review is to better understand the mechanism of SSRI-induced bruxism,
      as well as discuss alternative antidepressant options for treating depression and
      anxiety in patients with bruxism and TMD. Alternative classes of antidepressants
      reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic
      antidepressants, atypical antidepressants, and monoamine oxidase inhibitors.
      Findings indicate that dopamine agonists and buspirone are currently the most
      effective medications to treat the side effects of SSRI-induced bruxism, but
      results regarding the effectiveness of specific antidepressants that avoid
      bruxism altogether remain inconclusive.

PMID- 28492456
TI  - Calmer Life: A Hybrid Effectiveness-implementation Trial for Late-life Anxiety
      Conducted in Low-income, Mental Health-Underserved Communities.
AB  - OBJECTIVE: Anxiety is common among older adults and is associated with multiple
      negative outcomes. Late-life anxiety is usually unrecognized by providers and
      undertreated, although evidence supports the effectiveness of psychosocial
      treatment. Access to mental health care is especially poor among African American
      seniors. New treatment models are needed to expand the reach of mental health
      care to minority elders. METHODS: Our article outlines a study designed to test
      the effectiveness and implementation potential of Calmer Life (CL), a community
      based, person-centered, flexible and culturally tailored intervention for late
      life anxiety and worry, offered in low-income, mental health-underserved and
      predominantly African American communities. CL is skills-based, but also includes
      resource counseling and an option to integrate religion/spirituality. The study
      population includes individuals 50 years of age and older who are experiencing
      high levels of worry. The program was developed in the context of a community
      academic partnership with organizations that provide services for seniors in
      underserved communities, and it trains nontraditional community providers to
      deliver the intervention. RESULTS: Study progress to date, challenges, and
      lessons learned are discussed. Data collection is ongoing, and study findings
      will be available in late 2017. CONCLUSIONS: CL will offer valuable information
      to help expand the reach of anxiety treatment among minority seniors living in
      underserved neighborhoods.

PMID- 28492457
TI  - The Role of Amantadine Withdrawal in 3 Cases of Treatment-Refractory Altered
      Mental Status.
AB  - Amantadine, which was originally developed as an antiviral medication, functions
      as a dopamine agonist in the central nervous system and consequently is utilized
      in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and
      neuroleptic malignant syndrome. For reasons that are not entirely understood,
      abrupt changes in amantadine dosage can produce a severe withdrawal syndrome.
      Existing medical literature describes case reports of amantadine withdrawal
      leading to delirium, which at times has progressed to neuroleptic malignant
      syndrome. Amantadine withdrawal may be under-recognized by mental health
      clinicians, which has the potential to lead to protracted hospital courses and
      suboptimal outcomes. The goal of this case series is to highlight the role of
      amantadine withdrawal in the cases of 3 medically complex patients with altered
      mental status. In the first case, the cognitive side effects of electroconvulsive
      therapy masked acute amantadine withdrawal in a 64-year-old man with Parkinson
      disease. In the second case, a 75-year-old depressed patient developed a
      catatonic delirium when amantadine was discontinued. Finally, a refractory case
      of neuroleptic malignant syndrome in a 57-year-old patient with schizoaffective
      disorder rapidly resolved with the reintroduction of outpatient amantadine. These
      cases highlight several learning objectives regarding amantadine withdrawal
      syndrome: First, it may be concealed by co-occurring causes of delirium in
      medically complex patients. Second, its symptoms are likely to be related to a
      cortical and limbic dopamine shortage, which may be reversed with
      electroconvulsive therapy or reintroduction of amantadine. Third, its clinical
      presentation may occur on a spectrum and may include features suggestive of
      delirium, catatonia, or neuroleptic malignant syndrome.

PMID- 28492458
TI  - Switching From the Oral to the Depot Formulation of a Medication: Clinically
      Relevant Pharmacokinetic Concepts and Considerations.
AB  - This column presents principles that will aid the prescriber in transitioning
      patients from an oral to a depot antipsychotic medication. The column covers the
      differences in the pharmacokinetics of oral versus depot formulations that are
      critical in making a smooth transition. Also discussed are some of the reasons to
      use these medications, which, in the author's opinion, are currently
      underutilized. This column focuses on the big picture and the fundamentals of
      oral versus depot formulations rather than comparing the relative merits or
      potential advantages of the various marketed depot formulations.

PMID- 28492459
TI  - Making Psychotherapy Great Again?
AB  - Psychotherapy never stopped being as "great" as other treatments. This column
      explores the evidence base for both psychotherapy and medications, using
      depression as a specific example. The limitations are comparable for
      psychotherapy and medication, with much of the evidence based on small degrees of
      "statistically significant" rather than "clinically meaningful" change. Our
      field's biomedical emphasis leads to a false assumption that most patients
      present with single disorders, when comorbidity is the rule rather than the
      exception. This false assumption contributes to limitations in the evidence base
      and in our ability to treat patients optimally.

PMID- 28492460
TI  - Performance Validity Testing in Neuropsychology: Methods for Measurement
      Development and Maximizing Diagnostic Accuracy.
AB  - In the first column in this 2-part series, Performance Validity Testing in
      Neuropsychology: Scientific Basis and Clinical Application-A Brief Review, the
      authors introduced performance validity tests (PVTs) and their function, provided
      a justification for why they are necessary, traced their ongoing endorsement by
      neuropsychological organizations, and described how they are used and interpreted
      by ever increasing numbers of clinical neuropsychologists. To enhance readers'
      understanding of these measures, this second column briefly describes common
      detection strategies used in PVTs as well as the typical methods used to validate
      new PVTs and determine cut scores for valid/invalid determinations. We provide a
      discussion of the latest research demonstrating how neuropsychologists can
      combine multiple PVTs in a single battery to improve sensitivity/specificity to
      invalid responding. Finally, we discuss future directions for the research and
      application of PVTs.

PMID- 28492461
TI  - Overcoming Barriers to Initiating Medication-assisted Treatment for Heroin Use
      Disorder in a General Medical Hospital: A Case Report and Narrative Literature
      Review.
AB  - Deaths due to heroin overdoses are increasing and are the leading cause of death
      among intravenous heroin users. Although medication-assisted treatment (MAT)
      improves morbidity and mortality in patients with opioid use disorders, it is
      underutilized. Most efforts to expand access to MAT have focused on outpatient
      settings. Although the inpatient medical setting presents a critical opportunity
      to initiate treatment, general hospitals are often unfamiliar with MAT, creating
      a number of barriers to its use. In this report, we describe the case of a woman
      with heroin use disorder who was initiated on buprenorphine maintenance treatment
      while hospitalized for cardiac disease related to her intravenous heroin use.
      Barriers to initiating buprenorphine in this case included patient, practitioner,
      and organizational factors, and, ultimately, shared misperceptions about the
      feasibility of administering buprenorphine in a general medical hospital. These
      barriers were addressed, buprenorphine was initiated, and the patient
      demonstrated reduced craving, improved postoperative pain control, improved
      overall well-being, increased engagement in discharge planning, and acceptance of
      referral for addiction specialty aftercare. Our experience with this patient
      suggests that it is feasible to initiate buprenorphine in acute medical settings
      and that such treatment can improve patient outcomes. Our review of the
      literature reveals emerging evidence supporting the value of this practice.

PMID- 28492462
TI  - Synthetic Cannabinoids Use in Elderly Patients.
AB  - Synthetic cannabinoids are becoming a public health concern. No data are
      apparently available concerning use of synthetic cannabinoids in the elderly. We
      report two cases of elderly individuals who used synthetic cannabinoids and were
      admitted to a psychiatric hospital.

PMID- 28492463
TI  - Impact of an Alcohol Withdrawal Treatment Pathway on Hospital Length of Stay: A
      Retrospective Observational Study Comparing Pre and Post Pathway Implementation.
AB  - OBJECTIVE: To determine if the implementation of a hospital-specific alcohol
      withdrawal treatment pathway used in a medical-surgical patient population
      decreased hospital length of stay (LOS) compared with the standard of care.
      METHODS: This retrospective observational study, conducted in a large academic
      tertiary care hospital, involved 582 subjects who met criteria for study
      inclusion, with 275 subjects in the 2010 cohort and 307 in the 2012 cohort. The
      Alcohol Withdrawal Project Team was formed with the goal of creating a
      standardized approach to the recognition and treatment of alcohol withdrawal at
      Duke University Hospital. The group created a computerized physician order entry
      alcohol withdrawal treatment pathway with 4 possible treatment paths chosen on
      the basis of current withdrawal symptoms, vital signs, and alcohol withdrawal
      history. The 4 treatment paths are 1 prophylaxis; 2 mild-to-moderate withdrawal;
      3 moderate-to-severe withdrawal, and 4 severe withdrawal/alcohol withdrawal
      delirium. Each treatment path corresponds to a different lorazepam dose and dose
      schedule and symptom assessment. This pathway was implemented in the hospital at
      the end of 2011. RESULTS: Using a Cox proportional hazards model and adjusting
      for covariates, there was a 1 day [95% confidence interval (CI), 1-2 d] reduction
      in median hospital LOS between the 2010 and 2012 cohorts, 5 versus 4 days,
      respectively. The average ratio in hospital LOS between the 2 cohorts was 1.25
      (95% CI, 1.25-1.67). The CI was estimated by bootstrapping and indicated a
      significantly longer LOS in the 2010 cohort compared with the 2012 cohort.
      Nonsignificant changes were found in the proportion of subjects admitted to the
      intensive care unit (24% in 2010 vs. 29.3% in 2012), LOS in the intensive care
      unit (7.1+/-8 d in 2010 vs. 5.6+/-6.9 d in 2012), and proportion of patients
      discharged with a diagnosis of delirium tremens (17.8% in 2010 vs. 15.3% in
      2012). CONCLUSIONS: This study demonstrates the successful implementation of an
      alcohol withdrawal treatment pathway in a medical-surgical population
      hospitalized in a large tertiary care facility with significant impact on
      hospital LOS.

PMID- 28492464
TI  - Validity of Forced Eyelid Closure Test: A Novel Clinical Screening Test for
      Ocular Myasthenia Gravis.
AB  - BACKGROUND: Forced eyelid closure test (FECT) is a clinical screening test
      developed from the original Cogan lid twitch (CLT) sign to assist in the
      diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and
      specificity of FECT compared with CLT and benchmarked to standard diagnostic
      tests. METHODS: This study was a retrospective chart review of 48 patients using
      electronic medical records of those that presented with ptosis and/or diplopia at
      Doheny Eye Institute, University of California, Los Angeles between February 2015
      and April 2016. Patients without FECT testing were excluded. FECT and CLT
      results, and final diagnosis were recorded. To perform FECT, the patient was
      asked to squeeze his or her eyelids shut for 5-10 seconds then open quickly and
      fixate in primary position. The excessive upward overshoot of eyelids movement
      indicated a positive FECT. The test was performed by a neuro-ophthalmologist
      before establishing the diagnosis. Patients who had equivocal test results and/or
      inconclusive final diagnosis were excluded. RESULTS: Of the 48 patients studied,
      18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG
      (83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48
      patients, 35 patients also had a documented CLT result (72.9%). CLT was positive
      in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24
      patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity
      of FECT were 94% and 91% (joint 95% confidence region: sensitivity * specificity
      = [0.70, 1] * [0.75, 1]). The relative true-positive fraction (rTPF) between FECT
      and CLT was 1.15; the relative false-positive fraction was 1.31. CONCLUSIONS:
      FECT is a simple clinical screening test with good sensitivity and specificity
      for OMG.

PMID- 28492465
TI  - Mitigation of Patulin in Fresh and Processed Foods and Beverages.
AB  - Patulin is a mycotoxin of food safety concern. It is produced by numerous species
      of fungi growing on fruits and vegetables. Exposure to the toxin is connected to
      issues neurological, immunological, and gastrointestinal in nature. Regulatory
      agencies worldwide have established maximum allowable levels of 50 ug/kg in
      foods. Despite regulations, surveys continue to find patulin in commercial food
      and beverage products, in some cases, to exceed the maximum limits. Patulin
      content in food can be mitigated throughout the food processing chain. Proper
      handling, storage, and transportation of food can limit fungal growth and patulin
      production. Common processing techniques including pasteurisation, filtration,
      and fermentation all have an effect on patulin content in food but individually
      are not sufficient safety measures. Novel methods to remove or detoxify patulin
      have been reviewed. Non-thermal processing techniques such as high hydrostatic
      pressure, UV radiation, enzymatic degradation, binding to microorganisms, and
      chemical degradation all have potential but have not been optimised. Until
      further refinement of these methods, the hurdle approach to processing should be
      used where food safety is concerned. Future development should focus on
      determining the nature and safety of chemicals produced from the breakdown of
      patulin in treatment techniques.

PMID- 28492467
TI  - A Study of Pattern Prediction in the Monitoring Data of Earthen Ruins with the
      Internet of Things.
AB  - An understanding of the changes of the rammed earth temperature of earthen ruins
      is important for protection of such ruins. To predict the rammed earth
      temperature pattern using the air temperature pattern of the monitoring data of
      earthen ruins, a pattern prediction method based on interesting pattern mining
      and correlation, called PPER, is proposed in this paper. PPER first finds the
      interesting patterns in the air temperature sequence and the rammed earth
      temperature sequence. To reduce the processing time, two pruning rules and a new
      data structure based on an R-tree are also proposed. Correlation rules between
      the air temperature patterns and the rammed earth temperature patterns are then
      mined. The correlation rules are merged into predictive rules for the rammed
      earth temperature pattern. Experiments were conducted to show the accuracy of the
      presented method and the power of the pruning rules. Moreover, the Ming Dynasty
      Great Wall dataset was used to examine the algorithm, and six predictive rules
      from the air temperature to rammed earth temperature based on the interesting
      patterns were obtained, with the average hit rate reaching 89.8%. The PPER and
      predictive rules will be useful for rammed earth temperature prediction in
      protection of earthen ruins.

PMID- 28492468
TI  - Radon Mitigation Approach in a Laboratory Measurement Room.
AB  - Radon gas is the second leading cause of lung cancer, causing thousands of deaths
      annually. It can be a problem for people or animals in houses, workplaces,
      schools or any building. Therefore, its mitigation has become essential to avoid
      health problems and to prevent radon from interfering in radioactive
      measurements. This study describes the implementation of radon mitigation systems
      at a radioactivity laboratory in order to reduce interferences in the different
      works carried out. A large set of radon concentration samples is obtained from
      measurements at the laboratory. While several mitigation methods were taken into
      account, the final applied solution is explained in detail, obtaining thus very
      good results by reducing the radon concentration by 76%.

PMID- 28492469
TI  - A Blade Tip Timing Method Based on a Microwave Sensor.
AB  - Blade tip timing is an effective method for blade vibration measurements in
      turbomachinery. This method is increasing in popularity because it is non
      intrusive and has several advantages over the conventional strain gauge method.
      Different kinds of sensors have been developed for blade tip timing, including
      optical, eddy current and capacitance sensors. However, these sensors are
      unsuitable in environments with contaminants or high temperatures. Microwave
      sensors offer a promising potential solution to overcome these limitations. In
      this article, a microwave sensor-based blade tip timing measurement system is
      proposed. A patch antenna probe is used to transmit and receive the microwave
      signals. The signal model and process method is analyzed. Zero intermediate
      frequency structure is employed to maintain timing accuracy and dynamic
      performance, and the received signal can also be used to measure tip clearance.
      The timing method uses the rising and falling edges of the signal and an auto
      gain control circuit to reduce the effect of tip clearance change. To validate
      the accuracy of the system, it is compared experimentally with a fiber optic tip
      timing system. The results show that the microwave tip timing system achieves
      good accuracy.

PMID- 28492470
TI  - Improvement of Polylactide Properties through Cellulose Nanocrystals Embedded in
      Poly(Vinyl Alcohol) Electrospun Nanofibers.
AB  - Electrospun nanofibers of poly (vinyl alcohol) (PV) were obtained to improve
      dispersion of cellulose nanocrystals (CNC) within hydrophobic biopolymeric
      matrices, such as poly(lactic acid) (PLA). Electrospun nanofibers (PV/CNC)n were
      successfully obtained with a final concentration of 23% (w/w) of CNC.
      Morphological, structural and thermal properties of developed CNC and electrospun
      nanofibers were characterized. X-ray diffraction and thermal analysis revealed
      that the crystallinity of PV was reduced by the electrospinning process, and the
      incorporation of CNC increased the thermal stability of biodegradable nanofibers.
      Interactions between CNC and PV polymer also enhanced the thermal stability of
      CNC and improved the dispersion of CNC within the PLA matrix. PLA materials with
      CNC lyophilized were also casted in order to compare the properties with
      materials based on CNC containing nanofibers. Nanofibers and CNC were
      incorporated into PLA at three concentrations: 0.5%, 1% and 3% (CNC respect to
      polymer weight) and nanocomposites were fully characterized. Overall, nanofibers
      containing CNC positively modified the physical properties of PLA materials, such
      as the crystallinity degree of PLA which was greatly enhanced. Specifically,
      materials with 1% nanofiber 1PLA(PV/CNC)n presented highest improvements related
      to mechanical and barrier properties; elongation at break was enhanced almost
      four times and the permeation of oxygen was reduced by approximately 30%.

PMID- 28492471
TI  - Autonomous Sensors for Measuring Continuously the Moisture and Salinity of a
      Porous Medium.
AB  - The article describes a new field sensor to monitor continuously in situ moisture
      and salinity of a porous medium via measurements of its dielectric permittivity,
      conductivity and temperature. It intends to overcome difficulties and biases
      encountered with sensors based on the same sensitivity principle. Permittivity
      and conductivity are determined simultaneously by a self-balanced bridge, which
      measures directly the admittance of sensor electrodes in medium. All electric
      biases are reduced and their residuals taken into account by a physical model of
      the instrument, calibrated against reference fluids. Geometry electrode is
      optimized to obtain a well representative sample of the medium. The sensor also
      permits acquiring a large amount of data at high frequency (six points every
      hour, and even more) and to access it rapidly, even in real time, owing to
      autonomy capabilities and wireless communication. Ongoing developments intend to
      simplify and standardize present sensors. Results of field trials of prototypes
      in different environments are presented.

PMID- 28492466
TI  - NGF and Its Receptors in the Regulation of Inflammatory Response.
AB  - There is growing interest in the complex relationship between the nervous and
      immune systems and how its alteration can affect homeostasis and result in the
      development of inflammatory diseases. A key mediator in cross-talk between the
      two systems is nerve growth factor (NGF), which can influence both neuronal cell
      function and immune cell activity. The up-regulation of NGF described in inflamed
      tissues of many diseases can regulate innervation and neuronal activity of
      peripheral neurons, inducing the release of immune-active neuropeptides and
      neurotransmitters, but can also directly influence innate and adaptive immune
      responses. Expression of the NGF receptors tropomyosin receptor kinase A (TrkA)
      and p75 neurotrophin receptor (p75NTR) is dynamically regulated in immune cells,
      suggesting a varying requirement for NGF depending on their state of
      differentiation and functional activity. NGF has a variety of effects that can be
      either pro-inflammatory or anti-inflammatory. This apparent contradiction can be
      explained by considering NGF as part of an endogenous mechanism that, while
      activating immune responses, also activates pathways necessary to dampen the
      inflammatory response and limit tissue damage. Decreases in TrkA expression, such
      as that recently demonstrated in immune cells of arthritis patients, might
      prevent the activation by NGF of regulatory feed-back mechanisms, thus
      contributing to the development and maintenance of chronic inflammation.

PMID- 28492472
TI  - Molecular Surveillance of Cronobacter spp. Isolated from a Wide Variety of Foods
      from 44 Different Countries by Sequence Typing of 16S rRNA, rpoB and O-Antigen
      Genes.
AB  - Cronobacter spp. are emerging infectious bacteria that can cause acute meningitis
      and necrotizing enterocolitis in neonatal and immunocompromised individuals.
      Although this opportunistic human-pathogenic microorganism has been isolated from
      a wide variety of food and environmental samples, it has been primarily linked to
      foodborne outbreaks associated with powdered infant formula. The U.S. Food and
      Drug Administration use the presence of these microbes as one of the criteria to
      assess food adulteration and to implement regulatory actions. In this study, we
      have examined 195 aliquots of enrichments from the nine major categories of foods
      (including baby and medical food, dairy products, dried food, frozen food, pet
      food, produce, ready-to-eat snacks, seafood, and spices) from 44 countries using
      conventional microbiological and molecular techniques. The typical colonies of
      Cronobacter were then identified by VITEK2 and real-time PCR. Subsequently,
      sequence typing was performed on the 51 recovered Cronobacter isolates at the 16S
      rRNA, rpoB and seven O-antigen loci for species identification in order to
      accomplish an effective surveillance program for the control and prevention of
      foodborne illnesses.

PMID- 28492473
TI  - Acquisition and Neural Network Prediction of 3D Deformable Object Shape Using a
      Kinect and a Force-Torque Sensor.
AB  - The realistic representation of deformations is still an active area of research,
      especially for deformable objects whose behavior cannot be simply described in
      terms of elasticity parameters. This paper proposes a data-driven neural-network
      based approach for capturing implicitly and predicting the deformations of an
      object subject to external forces. Visual data, in the form of 3D point clouds
      gathered by a Kinect sensor, is collected over an object while forces are exerted
      by means of the probing tip of a force-torque sensor. A novel approach based on
      neural gas fitting is proposed to describe the particularities of a deformation
      over the selectively simplified 3D surface of the object, without requiring
      knowledge of the object material. An alignment procedure, a distance-based
      clustering, and inspiration from stratified sampling support this process. The
      resulting representation is denser in the region of the deformation (an average
      of 96.6% perceptual similarity with the collected data in the deformed area),
      while still preserving the object's overall shape (86% similarity over the entire
      surface) and only using on average of 40% of the number of vertices in the mesh.
      A series of feedforward neural networks is then trained to predict the mapping
      between the force parameters characterizing the interaction with the object and
      the change in the object shape, as captured by the fitted neural gas nodes. This
      series of networks allows for the prediction of the deformation of an object when
      subject to unknown interactions.

PMID- 28492474
TI  - Fabrication of Silicon Nanobelts and Nanopillars by Soft Lithography for
      Hydrophobic and Hydrophilic Photonic Surfaces.
AB  - Soft lithography allows for the simple and low-cost fabrication of nanopatterns
      with different shapes and sizes over large areas. However, the resolution and the
      aspect ratio of the nanostructures fabricated by soft lithography are limited by
      the depth and the physical properties of the stamp. In this work, silicon
      nanobelts and nanostructures were achieved by combining soft nanolithography
      patterning with optimized reactive ion etching (RIE) in silicon. Using
      polymethylmethacrylate (PMMA) nanopatterned layers with thicknesses ranging
      between 14 and 50 nm, we obtained silicon nanobelts in areas of square
      centimeters with aspect ratios up to ~1.6 and linewidths of 225 nm. The soft
      lithographic process was assisted by a thin film of SiOx (less than 15 nm) used
      as a hard mask and RIE. This simple patterning method was also used to fabricate
      2D nanostructures (nanopillars) with aspect ratios of ~2.7 and diameters of ~200
      nm. We demonstrate that large areas patterned with silicon nanobelts exhibit a
      high reflectivity peak in the ultraviolet C (UVC) spectral region (280 nm) where
      some aminoacids and peptides have a strong absorption. We also demonstrated how
      to tailor the aspect ratio and the wettability of these photonic surfaces
      (contact angles ranging from 8.1 to 96.2 degrees ) by changing the RIE power
      applied during the fabrication process.

PMID- 28492475
TI  - Ambiguity Resolution for Phase-Based 3-D Source Localization under Fixed Uniform
      Circular Array.
AB  - Under fixed uniform circular array (UCA), 3-D parameter estimation of a source
      whose half-wavelength is smaller than the array aperture would suffer from a
      serious phase ambiguity problem, which also appears in a recently proposed phase
      based algorithm. In this paper, by using the centro-symmetry of UCA with an even
      number of sensors, the source's angles and range can be decoupled and a novel
      algorithm named subarray grouping and ambiguity searching (SGAS) is addressed to
      resolve angle ambiguity. In the SGAS algorithm, each subarray formed by two
      couples of centro-symmetry sensors can obtain a batch of results under different
      ambiguities, and by searching the nearest value among subarrays, which is always
      corresponding to correct ambiguity, rough angle estimation with no ambiguity is
      realized. Then, the unambiguous angles are employed to resolve phase ambiguity in
      a phase-based 3-D parameter estimation algorithm, and the source's range, as well
      as more precise angles, can be achieved. Moreover, to improve the practical
      performance of SGAS, the optimal structure of subarrays and subarray selection
      criteria are further investigated. Simulation results demonstrate the satisfying
      performance of the proposed method in 3-D source localization.

PMID- 28492476
TI  - A Case Study of Improving Yield Prediction and Sulfur Deficiency Detection Using
      Optical Sensors and Relationship of Historical Potato Yield with Weather Data in
      Maine.
AB  - In Maine, potato yield is consistent, 38 t.ha-1, for last 10 years except 2016
      (44 t.ha-1) which confirms that increasing the yield and quality of potatoes with
      current fertilization practices is difficult; hence, new or improvised agronomic
      methods are needed to meet with producers and industry requirements. Normalized
      difference vegetative index (NDVI) sensors have shown promise in regulating N as
      an in season application; however, using late N may stretch out the maturation
      stage. The purpose of the research was to test Trimble GreenSeeker(r) (TGS) and
      Holland Scientific Crop CircleTM ACS-430 (HCCACS-430) wavebands to predict potato
      yield, before the second hilling (6-8 leaf stage). Ammonium sulfate, S containing
      N fertilizer, is not advised to be applied on acidic soils but accounts for 60
      70% fertilizer in Maine's acidic soils; therefore, sensors are used on sulfur
      deficient site to produce sensor-bound S application guidelines before
      recommending non-S-bearing N sources. Two study sites investigated for this
      research include an S deficient site and a regular spot with two kinds of soils.
      Six N treatments, with both calcium ammonium nitrate and ammonium nitrate, under
      a randomized complete block design with four replications, were applied at
      planting. NDVI readings from both sensors were obtained at V8 leaf stages (8 leaf
      per plant) before the second hilling. Both sensors predict N and S deficiencies
      with a strong interaction with an average coefficient of correlation (r2) ~45.
      However, HCCACS-430 was observed to be more virtuous than TGS. The correlation
      between NDVI (from both sensors) and the potato yield improved using proprietor
      proxy leaf area index (PPLAI) from HCCACS-430, e.g., r2 value of TGS at Easton
      site improve from 48 to 60. Weather data affected marketable potato yield (MPY)
      significantly from south to north in Maine, especially precipitation variations
      that could be employed in the N recommendations at planting and in season
      application. This case study addresses a substantial need to revise potato N
      recommendations at planting and develop possible in season N recommendation using
      ground based active optical (GBAO) sensors.

PMID- 28492477
TI  - Measuring Tree Properties and Responses Using Low-Cost Accelerometers.
AB  - Trees play a crucial role in the water, carbon and nitrogen cycle on local,
      regional and global scales. Understanding the exchange of momentum, heat, water,
      and CO 2 between trees and the atmosphere is important to assess the impact of
      drought, deforestation and climate change. Unfortunately, ground measurements of
      tree properties such as mass and canopy interception of precipitation are often
      expensive or difficult due to challenging environments. This paper aims to
      demonstrate the concept of using robust and affordable accelerometers to measure
      tree properties and responses. Tree sway is dependent on mass, canopy structure,
      drag coefficient, and wind forcing. By measuring tree acceleration, we can relate
      the tree motion to external forcing (e.g., wind, precipitation and related canopy
      interception) and tree physical properties (e.g., mass, elasticity). Using five
      months of acceleration data of 19 trees in the Brazilian Amazon, we show that the
      frequency spectrum of tree sway is related to mass, canopy interception of
      precipitation, and canopy-atmosphere turbulent exchange.

PMID- 28492479
TI  - Fusion Based on Visible Light Positioning and Inertial Navigation Using Extended
      Kalman Filters.
AB  - With the rapid development of smart technology, the need for location-based
      services (LBS) increases every day. Since classical positioning technology such
      as GPS cannot satisfy the needs of indoor positioning, new indoor positioning
      technologies, such as Bluetooth, Wi-Fi, and Visible light communication (VLC),
      have already cut a figure. VLC positioning has been proposed because it has
      higher accuracy, costs less, and is easier to accomplish in comparison to the
      other indoor positioning technologies. However, the practicality of VLC
      positioning is limited since it is easily affected by multipath effects and the
      layout of LEDs. Thus, we propose a fusion positioning system based on extended
      Kalman filters, which can fuse the VLC position and the inertial navigation data.
      The accuracy of the fusion positioning system is in centimeters, which is better
      compared to the VLC-based positioning or inertial navigation alone. Furthermore,
      the fusion positioning system has high accuracy, saves energy, costs little, and
      is easy to install, making it a promising candidate for future indoor positioning
      applications.

PMID- 28492478
TI  - The Role of the Orbitofrontal and Dorsolateral Prefrontal Cortices in Aesthetic
      Preference for Art.
AB  - The search for the underlying neural activation that occurs during subjective
      aesthetic experiences of artwork has been enhanced through neuroimaging
      techniques. Recently, the dorsolateral prefrontal cortex, alongside the
      orbitofrontal cortex, have been implicated in aesthetic appreciation, and this is
      the focus of the present paper. Here, the validity of this conclusion is examined
      through the discussion of its neuroanatomical connections and functional
      properties. It is proposed that the experimental evidence challenges the view
      that this area could hold a privileged position in a brain network involved in
      aesthetic preference.

PMID- 28492480
TI  - Detection of Soil Nitrogen Using Near Infrared Sensors Based on Soil Pretreatment
      and Algorithms.
AB  - Soil nitrogen content is one of the important growth nutrient parameters of
      crops. It is a prerequisite for scientific fertilization to accurately grasp soil
      nutrient information in precision agriculture. The information about nutrients
      such as nitrogen in the soil can be obtained quickly by using a near-infrared
      sensor. The data can be analyzed in the detection process, which is
      nondestructive and non-polluting. In order to investigate the effect of soil
      pretreatment on nitrogen content by near infrared sensor, 16 nitrogen
      concentrations were mixed with soil and the soil samples were divided into three
      groups with different pretreatment. The first group of soil samples with strict
      pretreatment were dried, ground, sieved and pressed. The second group of soil
      samples were dried and ground. The third group of soil samples were simply dried.
      Three linear different modeling methods are used to analyze the spectrum,
      including partial least squares (PLS), uninformative variable elimination (UVE),
      competitive adaptive reweighted algorithm (CARS). The model of nonlinear partial
      least squares which supports vector machine (LS-SVM) is also used to analyze the
      soil reflectance spectrum. The results show that the soil samples with strict
      pretreatment have the best accuracy in predicting nitrogen content by near
      infrared sensor, and the pretreatment method is suitable for practical
      application.

PMID- 28492481
TI  - A Vision-Aided 3D Path Teaching Method before Narrow Butt Joint Welding.
AB  - For better welding quality, accurate path teaching for actuators must be achieved
      before welding. Due to machining errors, assembly errors, deformations, etc., the
      actual groove position may be different from the predetermined path. Therefore,
      it is significant to recognize the actual groove position using machine vision
      methods and perform an accurate path teaching process. However, during the
      teaching process of a narrow butt joint, the existing machine vision methods may
      fail because of poor adaptability, low resolution, and lack of 3D information.
      This paper proposes a 3D path teaching method for narrow butt joint welding. This
      method obtains two kinds of visual information nearly at the same time, namely 2D
      pixel coordinates of the groove in uniform lighting condition and 3D point cloud
      data of the workpiece surface in cross-line laser lighting condition. The 3D
      position and pose between the welding torch and groove can be calculated after
      information fusion. The image resolution can reach 12.5 MUm. Experiments are
      carried out at an actuator speed of 2300 mm/min and groove width of less than 0.1
      mm. The results show that this method is suitable for groove recognition before
      narrow butt joint welding and can be applied in path teaching fields of 3D
      complex components.

PMID- 28492483
TI  - PCVMZM: Using the Probabilistic Classification Vector Machines Model Combined
      with a Zernike Moments Descriptor to Predict Protein-Protein Interactions from
      Protein Sequences.
AB  - Protein-protein interactions (PPIs) are essential for most living organisms'
      process. Thus, detecting PPIs is extremely important to understand the molecular
      mechanisms of biological systems. Although many PPIs data have been generated by
      high-throughput technologies for a variety of organisms, the whole interatom is
      still far from complete. In addition, the high-throughput technologies for
      detecting PPIs has some unavoidable defects, including time consumption, high
      cost, and high error rate. In recent years, with the development of machine
      learning, computational methods have been broadly used to predict PPIs, and can
      achieve good prediction rate. In this paper, we present here PCVMZM, a
      computational method based on a Probabilistic Classification Vector Machines
      (PCVM) model and Zernike moments (ZM) descriptor for predicting the PPIs from
      protein amino acids sequences. Specifically, a Zernike moments (ZM) descriptor is
      used to extract protein evolutionary information from Position-Specific Scoring
      Matrix (PSSM) generated by Position-Specific Iterated Basic Local Alignment
      Search Tool (PSI-BLAST). Then, PCVM classifier is used to infer the interactions
      among protein. When performed on PPIs datasets of Yeast and H. Pylori, the
      proposed method can achieve the average prediction accuracy of 94.48% and 91.25%,
      respectively. In order to further evaluate the performance of the proposed
      method, the state-of-the-art support vector machines (SVM) classifier is used and
      compares with the PCVM model. Experimental results on the Yeast dataset show that
      the performance of PCVM classifier is better than that of SVM classifier. The
      experimental results indicate that our proposed method is robust, powerful and
      feasible, which can be used as a helpful tool for proteomics research.

PMID- 28492482
TI  - Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by
      Prenatal Alcohol Exposure.
AB  - Prenatal alcohol exposure causes persistent neuropsychiatric deficits included
      under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges
      from a cascade of intrinsic and extrinsic (involving cell-cell interactions and
      signaling) processes that are partially initiated and maintained through changes
      in chromatin structure. Prenatal alcohol exposure influences neuronal and
      astrocyte development, permanently altering brain connectivity. Prenatal alcohol
      exposure also alters chromatin structure through histone and DNA modifications.
      However, the data linking alcohol-induced differentiation changes with
      developmental alterations in chromatin structure remain to be elucidated. In the
      first part of this review, we discuss the sequence of chromatin structural
      changes involved in neural cell differentiation during normal development. We
      then discuss the effects of prenatal alcohol on developmental histone
      modifications and DNA methylation in the context of neurogenesis and
      astrogliogenesis. We attempt to synthesize the developmental literature with the
      FASD literature, proposing that alcohol-induced changes to chromatin structure
      account for altered neurogenesis and astrogliogenesis as well as altered neuron
      and astrocyte differentiation. Together these changes may contribute to the
      cognitive and behavioral abnormalities in FASD. Future studies using standardized
      alcohol exposure paradigms at specific developmental stages will advance the
      understanding of how chromatin structural changes impact neural cell fate and
      maturation in FASD.

PMID- 28492484
TI  - The Potential of Triterpenoids from Loquat Leaves (Eriobotrya japonica) for
      Prevention and Treatment of Skin Disorder.
AB  - The leaves of loquat (Eriobotrya japonica) possess high medicinal value and have
      been used as traditional medicines. However, there are no evidence-based studies
      on the skin-care effects of E. japonica leaves. To explore new biological
      activities of E. japonica leaves against skin disorder and to gain a better
      understanding of the chemical components associated with bioactivities, we
      evaluated 18 triterpenoids from E. japonica leaves on anti-melanogenesis, anti
      acne, anti-allergy and anti-aging activities. Our results revealed that eight
      compounds showed anti-melanogenesis activity, of which ursolic acid (1) and
      maslinic acid (7) were the most potent with the similar selective index to that
      of arbutin. Structure-activity relationship and possible mechanism of active
      compounds were proposed. Twelve compounds exhibited anti-acne effect; ursolic
      acid (1), maslinic acid (7), corosolic acid (8) and euscaphic acid (12) showed
      highest activities against P. acnes. Four compounds displayed anti-allergy and
      anti-inflammatory activity; 3-epicorosolic acid (9) and euscaphic acid (12)
      showed marked activity against beta-hexosaminidase release. Finally, ursolic acid
      (1), pomolic acid (10), colosolic acid (8) and its methylated derivative (6)
      exhibited the highest anti-aging activity by stimulating collagen and hyaluronic
      acid (HA) production. Our findings provide valuable evidence that E. japonica
      leaves have potential applications as ingredients of function foods or cosmetics
      for health benefits and a number of triterpenoids may play an important role in
      these bioactivities.

PMID- 28492486
TI  - A Human Activity Recognition System Based on Dynamic Clustering of Skeleton Data.
AB  - Human activity recognition is an important area in computer vision, with its wide
      range of applications including ambient assisted living. In this paper, an
      activity recognition system based on skeleton data extracted from a depth camera
      is presented. The system makes use of machine learning techniques to classify the
      actions that are described with a set of a few basic postures. The training phase
      creates several models related to the number of clustered postures by means of a
      multiclass Support Vector Machine (SVM), trained with Sequential Minimal
      Optimization (SMO). The classification phase adopts the X-means algorithm to find
      the optimal number of clusters dynamically. The contribution of the paper is
      twofold. The first aim is to perform activity recognition employing features
      based on a small number of informative postures, extracted independently from
      each activity instance; secondly, it aims to assess the minimum number of frames
      needed for an adequate classification. The system is evaluated on two publicly
      available datasets, the Cornell Activity Dataset (CAD-60) and the
      Telecommunication Systems Team (TST) Fall detection dataset. The number of
      clusters needed to model each instance ranges from two to four elements. The
      proposed approach reaches excellent performances using only about 4 s of input
      data (~100 frames) and outperforms the state of the art when it uses
      approximately 500 frames on the CAD-60 dataset. The results are promising for the
      test in real context.

PMID- 28492485
TI  - Sulfated Alginates as Heparin Analogues: A Review of Chemical and Functional
      Properties.
AB  - Heparin is widely recognized for its potent anticoagulating effects, but has an
      additional wide range of biological properties due to its high negative charge
      and heterogeneous molecular structure. This heterogeneity has been one of the
      factors in motivating the exploration of functional analogues with a more
      predictable modification pattern and monosaccharide sequence, that can aid in
      elucidating structure-function relationships and further be structurally
      customized to fine-tune physical and biological properties toward novel
      therapeutic applications and biomaterials. Alginates have been of great interest
      in biomedicine due to their inherent biocompatibility, gentle gelling conditions,
      and structural versatility from chemo-enzymatic engineering, but display limited
      interactions with cells and biomolecules that are characteristic of heparin and
      the other glycosaminoglycans (GAGs) of the extracellular environment. Here, we
      review the chemistry and physical and biological properties of sulfated alginates
      as structural and functional heparin analogues, and discuss how they may be
      utilized in applications where the use of heparin and other sulfated GAGs is
      challenging and limited.

PMID- 28492487
TI  - Application of Soluplus to Improve the Flowability and Dissolution of Baicalein
      Phospholipid Complex.
AB  - In this study, a novel ternary complex system (TCS) composed of baicalein,
      phospholipids, and Soluplus was prepared to improve the flowability and
      dissolution for baicalein phospholipid complex (BPC). TCS was characterized using
      differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray
      diffraction (PXRD), and scanning electron microscopy (SEM). The flowability,
      solubility, oil-water partition coefficient, in vitro dissolution, and in vivo
      pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data
      confirmed that the crystal form of baicalein disappeared in BPC and TCS.
      Furthermore, the angle of repose of TCS of 35 degrees  indicated an improvement
      in flowability, and solubility increased by approximately eight-fold in distilled
      water when TCS was compared with BPC (41.00 +/- 4.89 MUg/mL vs. 5.00 +/- 0.16
      MUg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5%
      SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity
      and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability
      with higher peak plasma concentration (25.55 MUg/mL vs. 6.05 MUg/mL) and
      increased AUC0-infinity (62.47 MUg.h/mL vs. 50.48 MUg.h/mL) with 123.75% relative
      bioavailability compared with BPC. Thus, Soluplus achieved the purpose of
      improving the flowability and solubility of baicalein phospholipid complexes. The
      application of Soluplus to phospholipid complexes has great potential.

PMID- 28492489
TI  - An Automatic Localization Algorithm for Ultrasound Breast Tumors Based on Human
      Visual Mechanism.
AB  - Human visual mechanisms (HVMs) can quickly localize the most salient object in
      natural images, but it is ineffective at localizing tumors in ultrasound breast
      images. In this paper, we research the characteristics of tumors, develop a
      classic HVM and propose a novel auto-localization method. Comparing to
      surrounding areas, tumors have higher global and local contrast. In this method,
      intensity, blackness ratio and superpixel contrast features are combined to
      compute a saliency map, in which a Winner Take All algorithm is used to localize
      the most salient region, which is represented by a circle. The results show that
      the proposed method can successfully avoid the interference caused by background
      areas of low echo and high intensity. The method has been tested on 400
      ultrasound breast images, among which 376 images succeed in localization. This
      means this method has a high accuracy of 94.00%, indicating its good performance
      in real-life applications.

PMID- 28492488
TI  - Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion
      in a Sheep Model: Critical Role of alpha1-Adrenergic Signaling.
AB  - BACKGROUND: Maintenance of brain circulation during shock is sufficient to
      prevent subcortical injury but the cerebral cortex is not spared. This suggests
      area-specific regulation of cerebral blood flow (CBF) during hemorrhage. METHODS:
      Cortical and subcortical CBF were continuously measured during blood loss (<=50%)
      and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean
      arterial blood pressure (MABP), heart rate and renal blood flow were also
      monitored. Urapidil was used for alpha1A-adrenergic receptor blockade in dosages,
      which did not modify the MABP-response to blood loss. Western blot and
      quantitative reverse transcription polymerase chain reactions were used to
      determine adrenergic receptor expression in brain arterioles. RESULTS: During
      hypovolemia subcortical CBF was maintained at 81 +/- 6% of baseline, whereas
      cortical CBF decreased to 40 +/- 4% (p < 0.001). Reperfusion led to peak CBFs of
      about 70% above baseline in both brain regions. alpha1A-Adrenergic blockade
      massively reduced subcortical CBF during hemorrhage and reperfusion, and
      prevented hyperperfusion during reperfusion in the cortex. alpha1A-mRNA
      expression was significantly higher in the cortex, whereas alpha1D-mRNA
      expression was higher in the subcortex (p < 0.001). CONCLUSIONS: alpha1
      Adrenergic receptors are critical for perfusion redistribution: activity of the
      alpha1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the
      alpha1D-receptor subtype may determine the magnitude of redistribution responses.

PMID- 28492490
TI  - The Association between Parent Diet Quality and Child Dietary Patterns in Nine-
      to Eleven-Year-Old Children from Dunedin, New Zealand.
AB  - Previous research investigating the relationship between parents' and children's
      diets has focused on single foods or nutrients, and not on global diet, which may
      be more important for good health. The aim of the study was to investigate the
      relationship between parental diet quality and child dietary patterns. A cross
      sectional survey was conducted in 17 primary schools in Dunedin, New Zealand.
      Information on food consumption and related factors in children and their primary
      caregiver/parent were collected. Principal component analysis (PCA) was used to
      investigate dietary patterns in children and diet quality index (DQI) scores were
      calculated in parents. Relationships between parental DQI and child dietary
      patterns were examined in 401 child-parent pairs using mixed regression models.
      PCA generated two patterns; 'Fruit and Vegetables' and 'Snacks'. A one unit
      higher parental DQI score was associated with a 0.03SD (CI: 0.02, 0.04) lower
      child 'Snacks' score. There was no significant relationship between 'Fruit and
      Vegetables' score and parental diet quality. Higher parental diet quality was
      associated with a lower dietary pattern score in children that was characterised
      by a lower consumption frequency of confectionery, chocolate, cakes, biscuits and
      savoury snacks. These results highlight the importance of parental modelling, in
      terms of their dietary choices, on the diet of children.

PMID- 28492491
TI  - Magnetic Cationic Amylose Nanoparticles Used to Deliver Survivin-Small
      Interfering RNA for Gene Therapy of Hepatocellular Carcinoma In Vitro.
AB  - Amylose is a promising nanocarrier for gene delivery in terms of its good
      biocompatibility and high transfection efficiency. Small interfering RNA against
      survivin (survivin-siRNA) can cause tumor apoptosis by silencing a hepatocellular
      carcinoma (HCC)-specific gene at the messenger RNA level. In this study, we
      developed a new class of folate-functionalized, superparamagnetic iron oxide
      (SPIO)-loaded cationic amylose nanoparticles to deliver survivin-siRNA to HCC
      cells. The cellular uptake of nanocomplexes, cytotoxicity, cell apoptosis, and
      gene suppression mediated by siRNA-complexed nanoparticles were tested. The
      results demonstrated that folate-functionalized, SPIO-loaded cationic amylose
      nanoparticles can mediate a specific and safe cellular uptake of survivin-siRNA
      with high transfection efficiency, resulting in a robust survivin gene
      downregulation in HCC cells. The biocompatible complex of cationic amylose could
      be used as an efficient, rapid, and safe gene delivery vector. Upon SPIO loading,
      it holds a great promise as a theranostic carrier for gene therapy of HCC.

PMID- 28492492
TI  - The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin
      Resistance, and Body Composition in Postmenopausal American Women: An Ancillary
      Study from a Multicenter Protein Supplementation Trial.
AB  - Controversy exists as to whether high glycemic index/glycemic load (GI/GL) diets
      increase the risk of chronic inflammation, which has been postulated as a
      pathogenic intermediary between such diets and age-related alterations in body
      composition and insulin resistance. We conducted an ancillary study to a
      randomized, double-blind trial comparing the effects of a whey protein supplement
      (PRO, n = 38) and a maltodextrin supplement (CHO, n = 46) on bone density to
      evaluate the impact of a calibrated increase in GI/GL on inflammation, insulin
      resistance, and body composition in a healthy aging population. Markers of
      inflammation, HOMA, body composition, and GI/GL (estimated from 3-day food
      records) were assessed at baseline and 18 months. By 18 months, the GL in the CHO
      group increased by 34%, 88.4 +/- 5.2 -> 118.5 +/- 4.9 and did not change in the
      PRO group, 86.5 +/- 4.1 -> 82.0 +/- 3.6 (p < 0.0001). Despite this change there
      were no differences in serum CRP, IL-6, or HOMA at 18 months between the two
      groups, nor were there significant associations between GL and inflammatory
      markers. However, trunk lean mass (p = 0.0375) and total lean mass (p = 0.038)
      were higher in the PRO group compared to the CHO group at 18 months There were
      also significant associations for GL and change in total fat mass (r = 0.3, p =
      0.01), change in BMI (r = 0.3, p = 0.005), and change in the lean-to-fat mass
      ratio (r = -0.3, p = 0.002). Our data suggest that as dietary GL increases within
      the moderate range, there is no detectable change in markers of inflammation or
      insulin resistance, despite which there is a negative effect on body composition.

PMID- 28492493
TI  - Hydration, Fluid Intake, and Related Urine Biomarkers among Male College Students
      in Cangzhou, China: A Cross-Sectional Study-Applications for Assessing Fluid
      Intake and Adequate Water Intake.
AB  - The objectives of this study were to assess the associations between fluid intake
      and urine biomarkers and to determine daily total fluid intake for assessing
      hydration status for male college students. A total of 68 male college students
      aged 18-25 years recruited from Cangzhou, China completed a 7-day cross-sectional
      study. From day 1 to day 7; all subjects were asked to complete a self
      administered 7-day 24-h fluid intake record. The foods eaten by subjects were
      weighed and 24-h urine was collected for three consecutive days on the last three
      consecutive days. On the sixth day, urine osmolality, specific gravity (USG), pH,
      and concentrations of potassium, sodium, and chloride was determined. Subjects
      were divided into optimal hydration, middle hydration, and hypohydration groups
      according to their 24-h urine osmolality. Strong relationships were found between
      daily total fluid intake and 24-h urine biomarkers, especially for 24-h urine
      volume (r = 0.76; p < 0.0001) and osmolality (r = 0.76; p < 0.0001). The
      percentage of the variances in daily total fluid intake (R2) explained by PLS
      (partial least squares) model with seven urinary biomarkers was 68.9%; two urine
      biomarkers-24-h urine volume and osmolality-were identified as possible key
      predictors. The daily total fluid intake for assessing optimal hydration was 2582
      mL, while the daily total fluid intake for assessing hypohydration was 2502 mL.
      Differences in fluid intake and urine biomarkers were found among male college
      students with different hydration status. A strong relationship existed between
      urine biomarkers and fluid intake. A PLS model identified that key variables for
      assessing daily total fluid intake were 24-h urine volume and osmolality. It was
      feasibility to use total fluid intake to judge hydration status.

PMID- 28492495
TI  - Immunotherapy for Colorectal Cancer.
AB  - The recent success of anti-PD1 drugs in metastatic colorectal cancer patients
      with mismatch repair deficiency generated overwhelming enthusiasm for
      immunotherapy in the disease. However, patients with mismatch repair deficient
      colorectal cancer represent only a small subset of the metastatic population.
      Current research focuses on advancing immunotherapy to earlier stages of the
      disease including adjuvant and first-line metastatic settings, and on inducing
      sensitivity to immune checkpoint inhibitor therapy through a combinatorial
      approach. Here, we review the contemporary understanding of the immune and
      molecular landscape in colorectal cancer and discuss ongoing clinical trials
      evaluating novel combination regimens based on immune checkpoint inhibitors.

PMID- 28492494
TI  - Nasal Irrigation: An Imprecisely Defined Medical Procedure.
AB  - Nasal irrigation (NI) is an old practice of upper respiratory tract care that
      likely originated in the Ayurvedic medical tradition. It is used alone or in
      association with other therapies in several conditions-including chronic
      rhinosinusitis and allergic rhinitis-and to treat and prevent upper respiratory
      tract infections, especially in children. However, despite it being largely
      prescribed in everyday clinical practice, NI is not included or is only briefly
      mentioned by experts in the guidelines for treatment of upper respiratory tract
      diseases. In this review, present knowledge about NI and its relevance in
      clinical practice is discussed to assist physicians in understanding the
      available evidence and the potential use of this medical intervention. Analysis
      of the literature showed that NI seems to be effective in the treatment of
      several acute and chronic sinonasal conditions. However, although in recent years
      several new studies have been performed, most of the studies that have evaluated
      NI have relevant methodologic problems. Only multicenter studies enrolling a
      great number of subjects can solve the problem of the real relevance of NI, and
      these studies are urgently needed. Methods for performing NI have to be
      standardized to determine which solutions, devices and durations of treatment are
      adequate to obtain favorable results. This seems particularly important for
      children that suffer a great number of sinonasal problems and might benefit
      significantly from an inexpensive and simple preventive and therapeutic measure
      such as NI.

PMID- 28492496
TI  - Chemical Composition of Laurencia obtusa Extract and Isolation of a New C15
      Acetogenin.
AB  - A new C15-acetogenin, sagonenyne (20), exhibiting an unusual single
      tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia
      obtusa collected on the Corsican coastline. Its structure was established by
      detailed NMR spectroscopic analysis, mass spectrometry, and comparison with
      literature data. Twenty-three known compounds were identified in the same extract
      by means of column chromatography steps, using a 13C-NMR computer aided method
      developed in our laboratory. In addition to sesquiterpenes, which represent the
      main chemical class of this extract, diterpenes, sterols, and C15-acetogenins
      were identified. The crude extract was submitted to a cytotoxicity assay and was
      particularly active against THP-1 cells, a human leukemia monocytic cell line.

PMID- 28492498
TI  - Assessment of Inheritance and Fitness Costs Associated with Field-Evolved
      Resistance to Cry3Bb1 Maize by Western Corn Rootworm.
AB  - The western corn rootworm, Diabrotica virgifera virgifera LeConte, is among the
      most serious insect pests of maize in North America. One strategy used to manage
      this pest is transgenic maize that produces one or more crystalline (Cry) toxins
      derived from the bacterium Bacillus thuringiensis (Bt). To delay Bt resistance by
      insect pests, refuges of non-Bt maize are grown in conjunction with Bt maize. Two
      factors influencing the success of the refuge strategy to delay resistance are
      the inheritance of resistance and fitness costs, with greater delays in
      resistance expected when inheritance of resistance is recessive and fitness costs
      are present. We measured inheritance and fitness costs of resistance for two
      strains of western corn rootworm with field-evolved resistance to Cry3Bb1 maize.
      Plant-based and diet-based bioassays revealed that the inheritance of resistance
      was non-recessive. In a greenhouse experiment, in which larvae were reared on
      whole maize plants in field soil, no fitness costs of resistance were detected.
      In a laboratory experiment, in which larvae experienced intraspecific and
      interspecific competition for food, a fitness cost of delayed larval development
      was identified, however, no other fitness costs were found. These findings of non
      recessive inheritance of resistance and minimal fitness costs, highlight the
      potential for the rapid evolution of resistance to Cry3Bb1 maize by western corn
      rootworm, and may help to improve resistance management strategies for this pest.

PMID- 28492500
TI  - An Introduction to the Toxins Special Issue on "Novel Pharmacological Inhibitors
      for Bacterial Protein Toxins".
AB  - n/a.

PMID- 28492497
TI  - Regulation of TH17 Cells and Associated Cytokines in Wound Healing, Tissue
      Regeneration, and Carcinogenesis.
AB  - Wound healing is a crucial process which protects our body against permanent
      damage and invasive infectious agents. Upon tissue damage, inflammation is an
      early event which is orchestrated by a multitude of innate and adaptive immune
      cell subsets including TH17 cells. TH17 cells and TH17 cell associated cytokines
      can impact wound healing positively by clearing pathogens and modulating mucosal
      surfaces and epithelial cells. Injury of the gut mucosa can cause fast expansion
      of TH17 cells and their induction from naive T cells through Interleukin (IL)-6,
      TGF-beta, and IL-1beta signaling. TH17 cells produce various cytokines, such as
      tumor necrosis factor (TNF)-alpha, IL-17, and IL-22, which can promote cell
      survival and proliferation and thus tissue regeneration in several organs
      including the skin, the intestine, and the liver. However, TH17 cells are also
      potentially pathogenic if not tightly controlled. Failure of these control
      mechanisms can result in chronic inflammatory conditions, such as Inflammatory
      Bowel Disease (IBD), and can ultimately promote carcinogenesis. Therefore, there
      are several mechanisms which control TH17 cells. One control mechanism is the
      regulation of TH17 cells via regulatory T cells and IL-10. This mechanism is
      especially important in the intestine to terminate immune responses and maintain
      homeostasis. Furthermore, TH17 cells have the potential to convert from a pro
      inflammatory phenotype to an anti-inflammatory phenotype by changing their
      cytokine profile and acquiring IL-10 production, thereby limiting their own
      pathological potential. Finally, IL-22, a signature cytokine of TH17 cells, can
      be controlled by an endogenous soluble inhibitory receptor, Interleukin 22
      binding protein (IL-22BP). During tissue injury, the production of IL-22 by TH17
      cells is upregulated in order to promote tissue regeneration. To limit the
      regenerative program, which could promote carcinogenesis, IL-22BP is upregulated
      during the later phase of regeneration in order to terminate the effects of IL
      22. This delicate balance secures the beneficial effects of IL-22 and prevents
      its potential pathogenicity. An important future goal is to understand the
      precise mechanisms underlying the regulation of TH17 cells during inflammation,
      wound healing, and carcinogenesis in order to design targeted therapies for a
      variety of diseases including infections, cancer, and immune mediated
      inflammatory disease.

PMID- 28492499
TI  - Bioactive Natural Products of Marine Sponges from the Genus Hyrtios.
AB  - Marine sponges are known as a rich source for novel bioactive compounds with
      valuable pharmacological potential. One of the most predominant sponge genera is
      Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios
      reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a
      number of undescribed species. Members of the genus Hyrtios are a rich source of
      natural products with diverse and valuable biological activities, represented by
      different chemical classes including alkaloids, sesterterpenes and
      sesquiterpenes. This review covers the literature until June 2016, providing a
      complete survey of all compounds isolated from the genus Hyrtios with their
      corresponding biological activities whenever applicable.

PMID- 28492501
TI  - Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic
      Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.
AB  - To get insight into still elusive pathomechanisms of pediatric obesity and non
      alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS
      studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and
      food preferences (Kid-Med). Intestinal permeability (IP), small intestinal
      bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance
      were investigated in forty children (mean age 9.8 years) categorized as normal
      weight (NW) or obese (body mass index <85th or >95th percentile, respectively) +/
      ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was
      increased in all obese children (p = 0.0022), IP preferentially in those with
      NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary
      metabolome correctly allocated children based on their obesity, NAFLD, visceral
      fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher
      levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients;
      and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter
      especially in children without NAFLD. The metabolic pathways of BCAA and/or their
      metabolites correlated with excess of visceral fat centimeters (leucine/oxo
      valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome
      analysis contributes to define a metabolic fingerprint of pediatric obesity and
      related NAFLD, by identifying metabolic pathways/metabolites reflecting typical
      obesity dietary habits and GLA perturbations.

PMID- 28492502
TI  - Caregiver Supervision Practices and Risk of Childhood Unintentional Injury
      Mortality in Bangladesh.
AB  - Unintentional injury-related mortality rate, including drowning among children
      under five, is disproportionately higher in low- and middle-income countries. The
      evidence links lapse of supervision with childhood unintentional injury deaths.
      We determined the relationship between caregiver supervision and unintentional
      injury mortality among children under five in rural Bangladesh. We conducted a
      nested, matched, case-control study within the cohort of a large-scale drowning
      prevention project in Bangladesh, "SOLID-Saving of Children's Lives from
      Drowning". From the baseline survey of the project, 126 cases (children under
      five with unintentional injury deaths) and 378 controls (alive children under
      five) were selected at case-control ratio of 1:3 and individually matched on
      neighborhood. The association between adult caregiver supervision and fatal
      injuries among children under five was determined in a multivariable conditional
      logistic regression analysis, and reported as adjusted matched odds ratio (MOR)
      with 95% confidence intervals (CIs). Children under five experiencing death due
      to unintentional injuries, including drowning, had 3.3 times increased odds of
      being unsupervised as compared with alive children (MOR = 3.3, 95% CI: 1.6-7.0),
      while adjusting for children's sex, age, socioeconomic index, and adult
      caregivers' age, education, occupation, and marital status. These findings are
      concerning and call for concerted, multi-sectoral efforts to design community
      level prevention strategies. Public awareness and promotion of appropriate adult
      supervision strategies are needed.

PMID- 28492504
TI  - Optical Sensing to Determine Tomato Plant Spacing for Precise Agrochemical
      Application: Two Scenarios.
AB  - The feasibility of automated individual crop plant care in vegetable crop fields
      has increased, resulting in improved efficiency and economic benefits. A systems
      based approach is a key feature in the engineering design of mechanization that
      incorporates precision sensing techniques. The objective of this study was to
      design new sensing capabilities to measure crop plant spacing under different
      test conditions (California, USA and Andalucia, Spain). For this study, three
      different types of optical sensors were used: an optical light-beam sensor (880
      nm), a Light Detection and Ranging (LiDAR) sensor (905 nm), and an RGB camera.
      Field trials were conducted on newly transplanted tomato plants, using an encoder
      as a local reference system. Test results achieved a 98% accuracy in detection
      using light-beam sensors while a 96% accuracy on plant detections was achieved in
      the best of replications using LiDAR. These results can contribute to the
      decision-making regarding the use of these sensors by machinery manufacturers.
      This could lead to an advance in the physical or chemical weed control on row
      crops, allowing significant reductions or even elimination of hand-weeding tasks.

PMID- 28492503
TI  - Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First
      Trimester Cytotrophoblast Cells.
AB  - The cytotrophoblast (CTB) cells of the human placenta have membrane receptors
      that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these,
      marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used
      synthetic receptors (SR) to study their effectiveness on the angiogenic profile
      of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used
      in this study were derived from first trimester chorionic villus tissue. Culture
      media of CTB cells treated with >=1 nM SR level revealed sFlt-1 (Soluble fms-like
      tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial
      growth factor) was significantly decreased in the culture media (* p < 0.05 for
      each) The AT2 receptor (Angiotensin II receptor type 2) expression was
      significantly upregulated in >=1 nM SR-treated CTB cells as compared to basal;
      however, the AT1 (Angiotensin II receptor, type 1) and VEGFR-1 (vascular
      endothelial growth factor receptor 1) receptor expression was significantly
      downregulated (* p < 0.05 for each). Our results show that the anti-proliferative
      and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS.
      The observed anti angiogenic activity of SR on CTB cells demonstrates that the
      functionalized-urea/thiourea molecules may be useful as potent inhibitors to
      prevent CTS-induced impairment of CTB cells.

PMID- 28492505
TI  - Mesoporous Silica Nanoparticles as Carriers for Intracellular Delivery of Nucleic
      Acids and Subsequent Therapeutic Applications.
AB  - Nucleic acids, including DNA, microRNA (miRNA), small interfering RNA (siRNA),
      and antisense oligonucleotide (ASO), are powerful gene regulators, which have
      been demonstrated as promising drug candidates for therapeutic treatments.
      Nevertheless, poor cellular membrane permeability and serum stability have
      greatly hindered the applications of nucleic acids in biomedicine. To address
      these issues, associate carriers that can encapsulate and protect nucleic acids
      are urgently required. Mesoporous silica nanoparticles (MSNs or MSNPs), which are
      nanomaterials with excellent biocompatibility, large surface area for
      functionalization, and tunable pore size for encapsulating different cargos, are
      emerging as novel and ideal biomaterials for different biomedical applications.
      In this review paper, we focus on the applications of MSNs in nucleic acid
      delivery and nucleic acid-guided therapeutic treatments. General strategies for
      the preparation of nucleic acid-MSN complexes will be firstly introduced,
      followed by a summary of recent applications of MSNs in nucleic acid delivery and
      nucleic acid-guided therapeutics.

PMID- 28492507
TI  - Core-Shell Magnetic Gold Nanoparticles for Magnetic Field-Enhanced Radio
      Photothermal Therapy in Cervical Cancer.
AB  - The combination of radiotherapy (RT) and photothermal therapy (PTT) has been
      considered an attractive strategy in cervical cancer treatment. However, it
      remains a challenge to simultaneously enhance the radio-sensitivity of tumor
      tissue, develop tumor tissue-focused radiation therapies and combine dual
      therapeutic modalities. In this study, core-shell type magnetic gold (Fe3O4@Au)
      nanoparticles are exploited to achieve the synergistic efficacy of radio
      photothermal therapy in cervical cancer. Fe3O4@Au nanoparticles (NPs) with
      uniform morphology exhibited superior surface plasmon resonance properties,
      excellent superparamagnetic properties, good biocompatibility and high
      photothermal conversion efficiency. For the in vitro tests, a low concentration
      of Fe3O4@Au NPs after a short period of near-infrared irradiation lead to the
      time-dependent death of cervical cancer cells. Further, the combination of RT and
      PTT induced synergistic anti-cancer effects in vitro. More importantly, an
      external magnetic field could significantly enhance the synergistic efficacy of
      Fe3O4@Au NPs by improving their internalization. Hence, the reported Fe3O4@Au NPs
      have the potential to be good nanoagents with excellent magnetic targeting
      ability for cervical cancer radio-photothermal treatment.

PMID- 28492506
TI  - Implementation of Objective PASC-Derived Taxon Demarcation Criteria for Official
      Classification of Filoviruses.
AB  - The mononegaviral family Filoviridae has eight members assigned to three genera
      and seven species. Until now, genus and species demarcation were based on
      arbitrarily chosen filovirus genome sequence divergence values (~50% for genera,
      ~30% for species) and arbitrarily chosen phenotypic virus or virion
      characteristics. Here we report filovirus genome sequence-based taxon demarcation
      criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool
      of the US National Center for Biotechnology Information (Bethesda, MD, USA).
      Comparison of all available filovirus genomes in GenBank using PASC revealed
      optimal genus demarcation at the 55-58% sequence diversity threshold range for
      genera and at the 23-36% sequence diversity threshold range for species. Because
      these thresholds do not change the current official filovirus classification,
      these values are now implemented as filovirus taxon demarcation criteria that may
      solely be used for filovirus classification in case additional data are absent. A
      near-complete, coding-complete, or complete filovirus genome sequence will now be
      required to allow official classification of any novel "filovirus."
      Classification of filoviruses into existing taxa or determining the need for
      novel taxa is now straightforward and could even become automated using a
      presented algorithm/flowchart rooted in RefSeq (type) sequences.

PMID- 28492508
TI  - Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene
      and Poorly Water-Soluble Drugs Naproxen and Ibuprofen.
AB  - The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes
      with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP)
      were investigated. The effects of the alkyl chain's length and the inner core of
      calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were
      explored. The inclusion complexes of Amphiphiles 1a-c with NAP and IBP increased
      the solubility of these drugs in aqueous media. The interaction of 1a-c with the
      drugs in aqueous media was investigated through fluorescence, molecular modeling,
      and 1H-NMR analysis. TEM studies further supported the formation of inclusion
      complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature
      of cailx[4]arene derivatives 1a-c were found to have a significant impact on the
      solubility of NAP and IBP in pure water.

PMID- 28492509
TI  - Transcriptomic Profiling of the Allorecognition Response to Grafting in the
      Demosponge Amphimedon queenslandica.
AB  - Sponges, despite their simple body plan, discriminate between self and nonself
      with remarkable specificity. Sponge grafting experiments simulate the effects of
      natural self or nonself contact under laboratory conditions. Here we take a
      transcriptomic approach to investigate the temporal response to self and nonself
      grafts in the marine demosponge Amphimedon queenslandica. Auto- and allografts
      were established, observed and sampled over a period of three days, over which
      time the grafts either rejected or accepted, depending on the identity of the
      paired individuals, in a replicable and predictable manner. Fourteen
      transcriptomes were generated that spanned the auto- and allograft responses.
      Self grafts fuse completely in under three days, and the process appears to be
      controlled by relatively few genes. In contrast, nonself grafting results in a
      complete lack of fusion after three days, and appears to involve a broad
      downregulation of normal biological processes, rather than the mounting of an
      intense defensive response.

PMID- 28492510
TI  - Special Issue: Ribozymes and RNA Catalysis.
AB  - Over the past 35 years, RNA has become a molecule of utmost interest for
      researchers in the life sciences. The many functions that RNA fulfills in the
      cellular machinery have been elucidated with constant progress, revealing a
      complex network of RNA-mediated regulation of key processes in the cellular life
      cycle [...].

PMID- 28492511
TI  - Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of
      Life.
AB  - Pregnant women and infants are at risk for selenium deficiency, which is known to
      have negative effects on immune and brain function. We have investigated selenium
      levels in 158 healthy never-pregnant women and in 114 pregnant and lactating
      women and their infants at age 6 months and related this to clinical outcomes
      during the first 6 months of life. Neurodevelopment was assessed with the
      parental questionnaire Ages and Stages (ASQ) at 6 months. A maternal selenium
      level <=0.90 umol/L in pregnancy week 18 was negatively related to infant
      neurodevelopment at 6 months (B = -20, p = 0.01), whereas a selenium level <=0.78
      umol/L in pregnancy week 36 was associated with an increased risk (odds ratio
      4.8) of having an infant infection during the first 6 weeks of life. A low
      maternal selenium status in pregnancy was found to be associated with an
      increased risk of infant infection during the first 6 weeks of life and a lower
      psychomotor score at 6 months. We suggest a cutoff for maternal serum selenium
      deficiency of 0.90 umol/L in pregnancy week 18 and 0.78 umol/L in pregnancy week
      36. This should be reevaluated in an intervention study.

PMID- 28492512
TI  - Aldosterone and Mineralocorticoid Receptors-Physiology and Pathophysiology.
AB  - Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which
      have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand,
      evolved much earlier, and are found in cartilaginous and bony fish, presumptive
      ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone,
      and cortisol; in epithelia, despite much higher cortisol circulating levels,
      aldosterone selectively activates MRs by co-expression of the enzyme 11beta
      hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not
      expressed, MRs are overwhelmingly occupied but not activated by cortisol, which
      normally thus acts as an MR antagonist; in tissue damage, however, cortisol
      mimics aldosterone and acts as an MR agonist. The risk profile for primary
      aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure
      matched essential hypertensives. High levels of aldosterone per se are not the
      problem: in chronic sodium deficiency, as seen in the monsoon season in the
      highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but
      cause neither hypertension nor cardiovascular damage. Such damage occurs when
      aldosterone levels are out of the normal feedback control, and are
      inappropriately elevated for the salt status of the individual (or experimental
      animal). The question thus remains of how excess salt can synergize with elevated
      aldosterone levels to produce deleterious cardiovascular effects. One possible
      mechanism is through the agency of the elusive ouabain-like factors (OLFs). Such
      factors are secreted from the adrenal in response to ACTH (adrenalocortical
      tropic hormone), to angiotensin via AT2R, and-the polar opposite of aldosterone
      to sodium loading. They act on blood vessels to cause vasoconstriction and thus
      elevate blood pressure to dump excess sodium through pressure natriuresis. Their
      levels are chronically elevated in PA in response to the continually elevated
      sodium status, and they thus act to constrict coronary and systemic arteries. In
      the context of the elevated blood volume and total body sodium in a PA patient,
      this raises blood pressure and acts as the proximate cause of cardiovascular
      damage. If this is the case, it would appear to offer new insights into therapy
      for PA. One would be the use of digibindin, or its more recent successors as
      antagonists of OLFs acting on Na/K ATPase at the vessel wall. A second would be
      to routinely combine a low dose MR antagonist, an ENaC inhibitor, and sodium
      restriction as first-line therapy for bilateral aldosterone overproduction.
      Finally, for unilateral cases post-surgery, there is good reason to include low
      dose MRs in drug therapy if required, given the ability of cortisol in damaged
      blood vessels to mimic aldosterone vasoconstrictor action.

PMID- 28492514
TI  - Operating Point Self-Regulator for Giant Magneto-Impedance Magnetic Sensor.
AB  - The giant magneto-impedance (GMI) magnetic sensor based on the amorphous wire has
      been believed to be tiny dimensions, high sensitivity, quick response, and small
      power consumption. This kind of sensor is usually working under a bias magnetic
      field that is called the sensor's operating point. However, the changes in
      direction and intensity of the external magnetic field, or the changes in sensing
      direction and position of the sensor, will lead to fluctuations in operating
      point when the sensor is working without any magnetic shield. In this work, a GMI
      sensor based on the operating point self-regulator is designed to overcome the
      problem. The regulator is based on the compensated feedback control that can
      maintain the operating point of a GMI sensor in a uniform position. With the
      regulator, the GMI sensor exhibits a stable sensitivity regardless of the
      external magnetic field. In comparison with the former work, the developed
      operating point regulator can improve the accuracy and stability of the operating
      point and therefore decrease the noise and disturbances that are introduced into
      the GMI sensor by the previous self-regulation system.

PMID- 28492513
TI  - An AAAG-Rich Oligodeoxynucleotide Rescues Mice from Bacterial Septic Peritonitis
      by Interfering Interferon Regulatory Factor 5.
AB  - A previous study found that an AAAG-rich Oligodeoxynucleotide (ODN), designated
      as MS19, could lessen the acute lung inflammatory injury (ALII) in mice infected
      by influenza viruses. Bioinformatics analysis found that MS19 is consensus with
      the binding site of interferon regulatory factor 5 (IRF5) in the regulatory
      elements of pro-inflammatory genes. This study established a septic peritonitis
      model in Institute of Cancer Research (ICR) mice infected with Escherichia coli
      (E. coli), and found that MS19 prolonged the survival of the mice and down
      regulated the expression of inducible nitric oxide synthase (iNOS), interleukin-6
      (IL-6), and tumor necrosis factor alpha (TNF-alpha). In cultured RAW264.7 cells,
      MS19 significantly reduced the expression of iNOS, IRF5, IL-6, and TNF-alpha and
      inhibited the nuclear translocation of IRF5. This data may provide a new insight
      for understanding how MS19 reduces the excessive inflammatory responses in
      sepsis.

PMID- 28492515
TI  - Remote Sensing for Crop Water Management: From ET Modelling to Services for the
      End Users.
AB  - The experiences gathered during the past 30 years support the operational use of
      irrigation scheduling based on frequent multi-spectral image data. Currently, the
      operational use of dense time series of multispectral imagery at high spatial
      resolution makes monitoring of crop biophysical parameters feasible, capturing
      crop water use across the growing season, with suitable temporal and spatial
      resolutions. These achievements, and the availability of accurate forecasting of
      meteorological data, allow for precise predictions of crop water requirements
      with unprecedented spatial resolution. This information is greatly appreciated by
      the end users, i.e., professional farmers or decision-makers, and can be provided
      in an easy-to-use manner and in near-real-time by using the improvements achieved
      in web-GIS methodologies (Geographic Information Systems based on web
      technologies). This paper reviews the most operational and explored methods based
      on optical remote sensing for the assessment of crop water requirements,
      identifying strengths and weaknesses and proposing alternatives to advance
      towards full operational application of this methodology. In addition, we provide
      a general overview of the tools, which facilitates co-creation and collaboration
      with stakeholders, paying special attention to these approaches based on web-GIS
      tools.

PMID- 28492517
TI  - First Nations Approaches to Childhood Obesity: Healthy Lifestyles in Canada
      Compared with Alternatives for Alaska Native Communities.
AB  - Alaska Native and American Indian children have among the highest prevalence of
      obesity in the United States. Canadian Aboriginal populations including First
      Nations also have high rates of obesity but obesity rates among children are
      noticeably lower. We highlight some of the important differences between American
      and Canadian approaches to healthy lifestyles and Aboriginal/Native health,
      including diet and physical activity, which may in part explain the differences
      in obesity prevalence. Specifically, the Canadian government provides a food
      subsidy program to bring perishable fruits and vegetable to remote, rural
      Canadian areas and secondly supports the use of traditional foods and
      harvesting/gathering through a number of government supported programs. Lastly,
      there may be a better sense of community and overall life satisfaction for
      Aboriginals compared with Alaska Natives, in part because of the incorporation of
      healthcare and other services within the larger overall community, as opposed to
      separate services as is the case for Alaska Natives. This perspective provides
      insight into some of these potential differences.

PMID- 28492516
TI  - Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and
      Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated
      with First-Line Chemotherapy.
AB  - Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic
      and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study,
      we examined the prognostic role of cfDNA and CTCs, in separate and joint
      analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three
      patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were
      analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA
      quantification was performed by quantitative PCR (qPCR) whereas CTCs were
      isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated
      according to malignant features. Patients with baseline cfDNA higher than the
      median value (96.3 hTERT copy number) had a significantly worse overall survival
      (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits
      (CL) = 1.24-3.68; p-value = 0.006). Conversely, an inverse relationship between
      CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In
      addition, we found that in patients reporting stable disease (SD), the baseline
      cfDNA and CTCs were able to discriminate patients at high risk of poor survival.
      cfDNA demonstrated a more reliable biomarker than CTCs in the overall population.
      In the subgroup of SD patients, both biomarkers identified patients at high risk
      of poor prognosis who might deserve additional/alternative therapeutic
      interventions.

PMID- 28492518
TI  - Environmental Barriers to Participation of Preschool Children with and without
      Physical Disabilities.
AB  - Environment plays a vital role in affecting participation of young children in
      home, school, and community. Knowledge of environmental barriers helps to develop
      solutions or strategies that enable participation. The study compared the
      environmental barriers perceived by parents of preschool children with physical
      disabilities (PD, n = 142) and with typical development (TD, n = 192) in Taiwan.
      Parents identified environmental barriers by structured interview using the
      Chinese version of the Child and Adolescent Scale of Environment (CASE-C). The
      CASE-C is an 18-item measure of the impact of problems with physical, social, and
      attitudinal environmental features. Differences between the PD and TD groups in
      the summary scores for the CASE-C and the percentages of parents who perceived a
      problem for each item were examined by the analysis of covariance (ANCOVA) and
      Chi-square test. Parents of children with PD more often identified barriers
      related to family resources and community programs or services, social attitudes,
      assistance and supports outside of home, physical design of home and community,
      transportation, and assistive devices or equipment. Greater impacts of barriers
      were also reported by parents of preschool children with PD. Our findings provide
      evidence of environmental barriers that inform practice and policies to modify
      the barriers and provide an accessible and inclusive environment for families
      with young children.

PMID- 28492520
TI  - An ecologically-controlled exoskeleton can improve balance recovery after
      slippage.
AB  - The evolution to bipedalism forced humans to develop suitable strategies for
      dynamically controlling their balance, ensuring stability, and preventing
      falling. The natural aging process and traumatic events such as lower-limb loss
      can alter the human ability to control stability significantly increasing the
      risk of fall and reducing the overall autonomy. Accordingly, there is an urgent
      need, from both end-users and society, for novel solutions that can counteract
      the lack of balance, thus preventing falls among older and fragile citizens. In
      this study, we show a novel ecological approach relying on a wearable robotic
      device (the Active Pelvis Orthosis, APO) aimed at facilitating balance recovery
      after unexpected slippages. Specifically, if the APO detects signs of balance
      loss, then it supplies counteracting torques at the hips to assist balance
      recovery. Experimental tests conducted on eight elderly persons and two
      transfemoral amputees revealed that stability against falls improved due to the
      "assisting when needed" behavior of the APO. Interestingly, our approach required
      a very limited personalization for each subject, and this makes it promising for
      real-life applications. Our findings demonstrate the potential of closed-loop
      controlled wearable robots to assist elderly and disabled subjects and to improve
      their quality of life.

PMID- 28492521
TI  - Coinjection of IL2 DNA enhances E7-specific antitumor immunity elicited by
      intravaginal therapeutic HPV DNA vaccination with electroporation.
AB  - The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines
      represent an appealing treatment method against HPV-associated cervical cancer
      owing to their safety and durability. Previously, we created a therapeutic HPV
      DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin
      (CRT/E7), which we showed could generate significant E7-specific cytotoxic T
      lymphocyte (CTL)-mediated antitumor immune responses against HPV16 oncogenes
      expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of
      intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation. In
      addition, we examined whether coadministration of DNA-encoding interleukin 2
      (IL2) with the pcDNA3-CRT/E7 could improve the T-cell responses elicited by
      pcDNA3-CRT/E7. TC-1 tumor-bearing mice vaccinated intravaginally with both pcDNA3
      CRT/E7 and IL2 DNA followed by electroporation induced stronger local antitumor
      CTL response in comparison to mice that received other treatment regimens.
      Additionally, we found that coadministration of IL2 DNA with pcDNA3-CRT/E7
      modified the tumor microenvironment by decreasing the population of regulatory T
      cells and myeloid-derived suppressor cells relative to that of CTLs. Our data
      demonstrate the translational potential of local administration of IL2 and pcDNA3
      CRT/E7 followed by electroporation in treating cervicovaginal tumors.

PMID- 28492519
TI  - Theranostic Probes for Targeting Tumor Microenvironment: An Overview.
AB  - Long gone is the time when tumors were thought to be insular masses of cells,
      residing independently at specific sites in an organ. Now, researchers gradually
      realize that tumors interact with the extracellular matrix (ECM), blood vessels,
      connective tissues, and immune cells in their environment, which is now known as
      the tumor microenvironment (TME). It has been found that the interactions between
      tumors and their surrounds promote tumor growth, invasion, and metastasis. The
      dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose
      a challenge for cancer diagnosis, drug design, and therapy. As TME is significant
      in enhancing tumor progression, it is vital to identify the different components
      in the TME such as tumor vasculature, ECM, stromal cells, and the lymphatic
      system. This review explores how these significant factors in the TME, supply
      tumors with the required growth factors and signaling molecules to proliferate,
      invade, and metastasize. We also examine the development of TME-targeted
      nanotheranostics over the recent years for cancer therapy, diagnosis, and
      anticancer drug delivery systems. This review further discusses the limitations
      and future perspective of nanoparticle based theranostics when used in
      combination with current imaging modalities like Optical Imaging, Magnetic
      Resonance Imaging (MRI) and Nuclear Imaging (Positron Emission Tomography (PET)
      and Single Photon Emission Computer Tomography (SPECT)).

PMID- 28492523
TI  - Evaluation of identifier field agreement in linked neonatal records.
AB  - OBJECTIVE: To better address barriers arising from missing and unreliable
      identifiers in neonatal medical records, we evaluated agreement and discordance
      among traditional and non-traditional linkage fields within a linked neonatal
      data set. STUDY DESIGN: The retrospective, descriptive analysis represents
      infants born from 2013 to 2015. We linked children's hospital neonatal physician
      billing records to newborn medical records originating from an academic delivery
      hospital and evaluated rates of agreement, discordance and missingness for a set
      of 12 identifier field pairs used in the linkage algorithm. RESULTS: We linked
      7293 of 7404 physician billing records (98.5%), all of which were deemed valid
      upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non
      matching identifier pairs. Only 4.8% had complete agreement among all 12
      identifier pairs. CONCLUSION: Our approach to selection of linkage variables and
      data formatting preparatory to linkage have generalizability, which may inform
      future neonatal and perinatal record linkage efforts.

PMID- 28492522
TI  - Impact of brain injury on functional measures of amplitude-integrated EEG at term
      equivalent age in premature infants.
AB  - OBJECTIVE: To evaluate the association between qualitative and quantitative
      amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain
      injury on magnetic resonance imaging (MRI) in preterm infants. STUDY DESIGN: A
      cohort of premature infants born at <30 weeks of gestation and with moderate-to
      severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of
      gestational age-matched control infants also born at <30 weeks of gestation with
      none/mild injury on MRI was also recruited. Quantitative aEEG measures, including
      maximum and minimum amplitudes, bandwidth span and spectral edge frequency
      (SEF90), were calculated using an offline software package. The aEEG recordings
      were qualitatively scored using the Burdjalov system. MRI scans, performed on the
      same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42)
      weeks and were scored for abnormality in a blinded manner using an established
      MRI scoring system. RESULTS: Twenty-eight (46.7%) infants had a normal MRI or
      mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain
      abnormality. Univariate regression analysis demonstrated an association between
      severity of brain abnormality and quantitative measures of left and right SEF90
      and bandwidth span (beta=-0.38, -0.40 and 0.30, respectively) and qualitative
      measures of cyclicity, continuity and total Burdjalov score (beta=-0.10, -0.14
      and -0.12, respectively). After correcting for confounding variables, the
      relationship between MRI abnormality score and aEEG measures of SEF90, bandwidth
      span and Burdjalov score remained significant. CONCLUSION: Brain abnormalities on
      MRI at TEA in premature infants are associated with abnormalities on term aEEG
      measures, suggesting that anatomical brain injury may contribute to delay in
      functional brain maturation as assessed using aEEG.

PMID- 28492524
TI  - Sociodemographic and attitudinal predictors of simultaneous and redundant
      multiple marker and cell-free DNA screening among women aged ?35 years.
AB  - OBJECTIVE: To identify characteristics associated with undergoing cell-free DNA
      (cfDNA) and multiple marker screening (MMS) simultaneously or redundantly (after
      receiving negative results from the first screening test) among women aged ?35
      years. STUDY DESIGN: Participants presenting for prenatal testing completed a
      questionnaire that included measures of pregnancy worry and attitudes toward
      potential testing outcomes; data on prenatal test use was obtained via medical
      record review. We used multivariable logistic regression to identify factors
      associated with redundant or simultaneous screening. RESULTS: Among 164
      participants, 69 (42.1%) had cfDNA redundantly (n=51) to, or simultaneously
      (n=18) with, MMS. Compared with the 46 MMS-negative women who did not undergo
      further testing, those who underwent redundant or simultaneous cfDNA/MMS
      screening were more likely to have annual family incomes >$150 000, to feel
      having a miscarriage would be worse than having an intellectually disabled child,
      to desire comprehensive testing for intellectual disability and to have more
      pregnancy worry. CONCLUSION: Providers who counsel patients on prenatal
      aneuploidy screening tests should explain the appropriate utilization of these
      screening tests to avoid unnecessary or minimally informative use of multiple
      tests.

PMID- 28492525
TI  - Neonatal sepsis in rural India: timing, microbiology and antibiotic resistance in
      a population-based prospective study in the community setting.
AB  - OBJECTIVE: To examine the timing and microbiology of neonatal sepsis in a
      population-based surveillance in the Indian community setting. STUDY DESIGN: All
      live born infants in 223 villages of Odisha state were followed at home for 60
      days. Suspect sepsis cases were referred to study hospitals for further
      evaluation including blood culture. RESULTS: Of 12 622 births, 842 were admitted
      with suspected sepsis of whom 95% were 4 to 60 days old. Culture-confirmed
      incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella
      predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high
      level of resistance to penicillin and ampicillin, moderate resistance to
      cephalosporins and extremely low resistance to Gentamicin and Amikacin was
      observed. CONCLUSION: The bacterial burden of sepsis in the Indian community is
      not high. Judicious choice of empiric antibiotics, antibiotic stewardship and
      alternate modalities should be considered for the management or prevention of
      neonatal sepsis in India.

PMID- 28492527
TI  - Single-cell template strand sequencing by Strand-seq enables the characterization
      of individual homologs.
AB  - The ability to distinguish between genome sequences of homologous chromosomes in
      single cells is important for studies of copy-neutral genomic rearrangements
      (such as inversions and translocations), building chromosome-length haplotypes,
      refining genome assemblies, mapping sister chromatid exchange events and
      exploring cellular heterogeneity. Strand-seq is a single-cell sequencing
      technology that resolves the individual homologs within a cell by restricting
      sequence analysis to the DNA template strands used during DNA replication. This
      protocol, which takes up to 4 d to complete, relies on the directionality of DNA,
      in which each single strand of a DNA molecule is distinguished based on its 5'-3'
      orientation. Culturing cells in a thymidine analog for one round of cell division
      labels nascent DNA strands, allowing for their selective removal during genomic
      library construction. To preserve directionality of template strands, genomic
      preamplification is bypassed and labeled nascent strands are nicked and not
      amplified during library preparation. Each single-cell library is multiplexed for
      pooling and sequencing, and the resulting sequence data are aligned, mapping to
      either the minus or plus strand of the reference genome, to assign template
      strand states for each chromosome in the cell. The major adaptations to
      conventional single-cell sequencing protocols include harvesting of daughter
      cells after a single round of BrdU incorporation, bypassing of whole-genome
      amplification, and removal of the BrdU+ strand during Strand-seq library
      preparation. By sequencing just template strands, the structure and identity of
      each homolog are preserved.

PMID- 28492529
TI  - CORRIGENDUM: ACMG recommendations for reporting of incidental findings in
      clinical exome and genome sequencing.

PMID- 28492526
TI  - Differentiation of cardiomyocytes and generation of human engineered heart
      tissue.
AB  - Since the advent of the generation of human induced pluripotent stem cells
      (hiPSCs), numerous protocols have been developed to differentiate hiPSCs into
      cardiomyocytes and then subsequently assess their ability to recapitulate the
      properties of adult human cardiomyocytes. However, hiPSC-derived cardiomyocytes
      (hiPSC-CMs) are often assessed in single-cell assays. A shortcoming of these
      assays is the limited ability to characterize the physiological parameters of
      cardiomyocytes, such as contractile force, due to random orientations. This
      protocol describes the differentiation of cardiomyocytes from hiPSCs, which
      occurs within 14 d. After casting, cardiomyocytes undergo 3D assembly. This
      produces fibrin-based engineered heart tissues (EHTs)-in a strip format-that
      generate force under auxotonic stretch conditions. 10-15 d after casting, the
      EHTs can be used for contractility measurements. This protocol describes parallel
      expansion of hiPSCs; standardized generation of defined embryoid bodies, growth
      factor and small-molecule-based cardiac differentiation; and standardized
      generation of EHTs. To carry out the protocol, experience in advanced cell
      culture techniques is required.

PMID- 28492530
TI  - A comprehensive strategy for exome-based preconception carrier screening.
AB  - PURPOSE: Whole-exome sequencing (WES) provides the possibility of genome-wide
      preconception carrier screening (PCS). Here, we propose a filter strategy to
      rapidly identify the majority of relevant pathogenic mutations. METHODS: Our
      strategy was developed using WES data from eight consanguineous and five fictive
      nonconsanguineous couples and was subsequently applied to 20 other fictive
      nonconsanguineous couples. Presumably pathogenic variants based on frequency and
      database annotations or generic characteristics and mutation type were selected
      in genes shared by the couple and in the female's X-chromosome. Unclassified
      variants were not included. RESULTS: This yielded an average of 29 (19-51)
      variants in genes shared by the consanguineous couples and 15 (6-30) shared by
      the nonconsanguineous couples. For X-linked variants, the numbers per female were
      3 (1-5) and 1 (0-3), respectively. Remaining variants were verified manually. The
      majority were able to be quickly discarded, effectively leaving true pathogenic
      variants. CONCLUSION: We conclude that WES is applicable for PCS, both for
      consanguineous and nonconsanguineous couples, with the remaining number of
      variants being manageable in a clinical setting. The addition of gene panels for
      filtering was not favorable because it resulted in missing pathogenic variants.
      It is important to develop and continuously curate databases with pathogenic
      mutations to further increase the sensitivity of WES-based PCS.Genet Med advance
      online publication 27 October 2016.

PMID- 28492531
TI  - Improving the evaluation of milestones for students completing a clinical
      genetics elective.

PMID- 28492532
TI  - Sherloc: a comprehensive refinement of the ACMG-AMP variant classification
      criteria.
AB  - PurposeThe 2015 American College of Medical Genetics and Genomics-Association for
      Molecular Pathology (ACMG-AMP) guidelines were a major step toward establishing a
      common framework for variant classification. In practice, however, several
      aspects of the guidelines lack specificity, are subject to varied
      interpretations, or fail to capture relevant aspects of clinical molecular
      genetics. A simple implementation of the guidelines in their current form is
      insufficient for consistent and comprehensive variant classification.MethodsWe
      undertook an iterative process of refining the ACMG-AMP guidelines. We used the
      guidelines to classify more than 40,000 clinically observed variants, assessed
      the outcome, and refined the classification criteria to capture exceptions and
      edge cases. During this process, the criteria evolved through eight major and
      minor revisions.ResultsOur implementation: (i) separated ambiguous ACMG-AMP
      criteria into a set of discrete but related rules with refined weights; (ii)
      grouped certain criteria to protect against the overcounting of conceptually
      related evidence; and (iii) replaced the "clinical criteria" style of the
      guidelines with additive, semiquantitative criteria.ConclusionSherloc builds on
      the strong framework of 33 rules established by the ACMG-AMP guidelines and
      introduces 108 detailed refinements, which support a more consistent and
      transparent approach to variant classification.

PMID- 28492534
TI  - Response to de Vries et al.

PMID- 28492533
TI  - Gene patents still alive and kicking: their impact on provision of genetic
      testing for long QT syndrome in the Canadian public health-care system.
AB  - PurposeAlthough the Supreme Court of the United States limited their availability
      in Association for Molecular Pathology v. Myriad Genetics, gene patents remain
      important around the world. We examine the situation in Canada, where gene
      patents continue to exist, in light of recent litigation relating to familial
      long QT syndrome (LQTS).MethodsWe conducted in-depth semistructured interviews
      with 25 stakeholders across five Canadian provinces and supplemented this with a
      case analysis of the litigation.ResultsThe majority of LQTS testing was carried
      out outside Canada. Rising costs prompted several provinces to attempt to
      repatriate testing. However, LQTS gene patents stymied efforts, particularly in
      provinces where testing was more centralized, increasing costs and lowering
      innovation. It was in this context that a hospital launched a test case against
      the LQTS patents, resulting in a novel agreement to free Canadian hospitals from
      the effects of patents.ConclusionOur analysis reveals a rapidly evolving genetic
      test provision landscape under pressure from gene patents, strained budgets and
      poor collaboration. The litigation resulted in a blueprint for free public use of
      gene patents throughout Canada's health-care system, but it will only have value
      if governments are proactive in its use.

PMID- 28492535
TI  - Response to Laissue et al.

PMID- 28492536
TI  - Quantifying family dissemination and identifying barriers to communication of
      risk information in Australian BRCA families.
AB  - PurposeRecommendations for BRCA1 and BRCA2 mutation carriers to disseminate
      information to at-risk relatives pose significant challenges. This study aimed to
      quantify family dissemination, to explain the differences between fully informed
      families (all relatives informed verbally or in writing) and partially informed
      families (at least one relative uninformed), and to identify dissemination
      barriers.MethodsBRCA1 and BRCA2 mutation carriers identified from four Australian
      hospitals (n=671) were invited to participate in the study. Distress was measured
      at consent using the Kessler psychological distress scale (K10). A structured
      telephone interview was used to assess the informed status of relatives,
      geographical location of relatives, and dissemination barriers. Family
      dissemination was quantified, and fully versus partially informed family
      differences were examined. Dissemination barriers were thematically coded and
      counted.ResultsA total of 165 families participated. Information had been
      disseminated to 81.1% of relatives. At least one relative had not been informed
      in 52.7% of families, 4.3% were first-degree relatives, 27.0% were second-degree
      relatives, and 62.0% were cousins. Partially informed families were significantly
      larger than fully informed families, had fewer relatives living in close
      proximity, and exhibited higher levels of distress. The most commonly recorded
      barrier to dissemination was loss of contact.ConclusionLarger, geographically
      diverse families have greater difficulty disseminating BRCA mutation risk
      information to all relatives. Understanding these challenges can inform future
      initiatives for communication, follow-up and support.

PMID- 28492537
TI  - Advantages and Some Remaining Challenges in Hereditary Gastrointestinal Cancer
      Panel Testing.
AB  - Colorectal cancer affects 1 in 20 men and women in their lifetime. About 30% of
      these cases have been shown to be familial while only about 5% are associated
      with a highly penetrant hereditary colon cancer syndrome. In many familial cases,
      however, no mutation in the commonly implicated CRC genes is found. With the
      development of next-generation sequencing, testing laboratories are now able to
      offer hereditary gastrointestinal panel testing, which allows for the
      simultaneous sequencing of a much broader set of genes associated with CRC. We
      discuss the advantages and disadvantages of such testing to inform best clinical
      practice.

PMID- 28492538
TI  - Drosophila caspase activity is required independently of apoptosis to produce
      active TNF/Eiger during nociceptive sensitization.
AB  - Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive
      (pain) sensitization in Drosophila and vertebrates. Nociceptive sensitization in
      Drosophila larvae following UV-induced tissue damage is accompanied by epidermal
      apoptosis and requires epidermal-derived TNF/Eiger and the initiator caspase,
      Dronc. Major gaps remain regarding TNF function in sensitization, including the
      relationship between apoptosis/tissue damage and TNF production, the downstream
      signaling in this context, and the target genes that modulate nociceptive
      behaviors. Here, apoptotic cell death and thermal nociceptive sensitization are
      genetically and procedurally separable in a Drosophila model of UV-induced
      nociceptive sensitization. Activation of epidermal Dronc induces TNF-dependent
      but effector caspase-independent nociceptive sensitization in the absence of UV.
      In addition, knockdown of Dronc attenuated nociceptive sensitization induced by
      full-length TNF/Eiger but not by a constitutively soluble form. UV irradiation
      induced TNF production in both in vitro and in vivo, but TNF secretion into
      hemolymph was not sufficient to induce thermal nociceptive sensitization.
      Downstream mediators of TNF-induced sensitization included two TNF receptor
      associated factors, a p38 kinase, and the transcription factor nuclear factor
      kappa B. Finally, sensory neuron-specific microarray analysis revealed downstream
      TNF target genes induced during thermal nociceptive sensitization. One of these,
      enhancer of zeste (E(z)), functions downstream of TNF during thermal nociceptive
      sensitization. Our findings suggest that an initiator caspase is involved in TNF
      processing/secretion during nociceptive sensitization, and that TNF activation
      leads to a specific downstream signaling cascade and gene transcription required
      for sensitization. These findings have implications for both the evolution of
      inflammatory caspase function following tissue damage signals and the action of
      TNF during sensitization in vertebrates.

PMID- 28492539
TI  - Non-junctional Cx32 mediates anti-apoptotic and pro-tumor effects via epidermal
      growth factor receptor in human cervical cancer cells.
AB  - The role of connexin proteins (Cx), which form gap junctions (GJ), in progression
      and chemotherapeutic sensitivity of cervical cancer (CaCx), is unclear. Using
      cervix specimens (313 CaCx, 78 controls) and CaCx cell lines, we explored
      relationships among Cx expression, prognostic variables and mechanisms that may
      link them. In CaCx specimens, Cx32 was upregulated and cytoplasmically localized,
      and three other Cx downregulated, relative to controls. Cx32 expression
      correlated with advanced FIGO staging, differentiation and increased tumor size.
      In CaCx cell lines, Cx32 expression suppressed streptonigrin/cisplatin-induced
      apoptosis in the absence of functional GJ. In CaCx specimens and cell lines,
      expression of Cx32 upregulated epidermal growth factor receptor (EGFR)
      expression. Inhibition of EGFR signaling abrogated the anti-apoptotic effect of
      Cx32 expression. In conclusion, upregulated Cx32 in CaCx cells produces anti
      apoptotic, pro-tumorigenic effects in vivo and vitro. Abnormal Cx32
      expression/localization in CaCx appears to be both a mechanism and biomarker of
      chemotherapeutic resistance.

PMID- 28492540
TI  - NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.
AB  - N-myc and STAT interactor (NMI) has been proved to bind to different
      transcription factors to regulate a variety of signaling mechanisms including DNA
      damage, cell cycle and epithelial-mesenchymal transition. However, the role of
      NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In
      this study, we investigated the regulation of NMI on CSCs traits in breast cancer
      and uncovered the underlying molecular mechanisms. We found that NMI was lowly
      expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of
      NMI promoted CSCs traits while its overexpression inhibited CSCs traits,
      including the expression of CSC-related markers, the number of CD44+CD24- cell
      populations and the ability of mammospheres formation. We also found that NMI
      mediated regulation of BCSCs traits was at least partially realized through the
      modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while
      its overexpression downregulated hTERT in breast cancer cells, and the changes in
      CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The
      in vivo study also validated that NMI knockdown promoted breast cancer growth by
      upregulating hTERT signaling in a mouse model. Moreover, further analyses for the
      clinical samples demonstrated that NMI expression was negatively correlated with
      hTERT expression and the low NMI/high hTERT expression was associated with the
      worse status of clinical TNM stages in breast cancer patients. Furthermore, we
      demonstrated that the interaction of YY1 protein with NMI and its involvement in
      NMI-mediated transcriptional regulation of hTERT in breast cancer cells.
      Collectively, our results provide new insights into understanding the regulatory
      mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a
      potential therapeutic target for breast cancers.

PMID- 28492541
TI  - Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor
      bearing hosts through prevention of ROS-mediated apoptosis.
AB  - Immunotherapy aiming to rescue or boost antitumor immunity is an emerging
      strategy for treatment of cancers. The efficacy of immunotherapy is strongly
      controlled by the immunological milieu of cancer patients. Myeloid-derived
      suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with
      immunosuppressive functions accumulating in individuals during tumor progression.
      The signaling mechanisms of MDSC activation have been well studied. However,
      there is little known about the metabolic status of MDSCs and the physiological
      role of their metabolic reprogramming. In this study, we discovered that myeloid
      cells upregulated their glycolytic genes when encountered with tumor-derived
      factors. MDSCs exhibited higher glycolytic rate than their normal cell
      compartment did, which contributed to the accumulation of the MDSCs in tumor
      bearing hosts. Upregulation of glycolysis prevented excess reactive oxygen
      species (ROS) production by MDSCs, which protected MDSCs from apoptosis. Most
      importantly, we identified the glycolytic metabolite, phosphoenolpyruvate (PEP),
      as a vital antioxidant agent able to prevent excess ROS production and therefore
      contributed to the survival of MDSCs. These findings suggest that glycolytic
      metabolites have important roles in the modulation of fitness of MDSCs and could
      be potential targets for anti-MDSC strategy. Targeting MDSCs with analogs of
      specific glycolytic metabolites, for example, 2-phosphoglycerate or PEP may
      diminish the accumulation of MDSCs and reverse the immunosuppressive milieu in
      tumor-bearing individuals.

PMID- 28492542
TI  - LncRNA HOTAIR regulates HIF-1alpha/AXL signaling through inhibition of miR-217 in
      renal cell carcinoma.
AB  - Long non-coding RNA HOTAIR was regarded as an oncogene in multiple cancers.
      Previous studies have shown that HOTAIR is involved in the proliferation and
      tumorigenesis of renal carcinoma cells, while microRNA (miR)-217 functions as a
      tumor suppressor in renal cell carcinoma (Rcc). However, the underlying molecular
      mechanism of HOTAIR in Rcc, especially in association with miR-217, has not been
      studied. In this study, we first demonstrated that HOTAIR expression was
      upregulated, which was correlated with tumor progression, and miR-217
      downregulated in Rcc tissues and cells. Importantly, HOTAIR expression was
      negatively correlated with miR-217 expression in Rcc tissues. Gain- and loss-of
      function of HOTAIR revealed that HOTAIR functioned as a ceRNA for miR-217 to
      facilitate HIF-1alpha expression and then upregulated AXL level promoting Rcc
      proliferation, migration, and EMT process, and inhibiting apoptosis. Furthermore,
      HOTAIR knockdown suppressed tumor growth and reduced the expression of
      proliferation antigen ki-67, HIF-1alpha, and AXL, but upregulated the expression
      of miR-217 in vivo. Finally, with AXL inhibitor BGB324, we confirmed that HOTAIR
      promoted Rcc activity through AXL signaling both in vitro and in vivo. In
      conclusion, these results suggest that HOTAIR promotes Rcc tumorigenesis via miR
      217/HIF-1alpha/AXL signaling, which may provide a new target for the diagnosis
      and therapy of Rcc disease.

PMID- 28492543
TI  - BASP1 interacts with oestrogen receptor alpha and modifies the tamoxifen
      response.
AB  - Tamoxifen binds to oestrogen receptor alpha (ERalpha) to elicit distinct
      responses that vary by cell/tissue type and status, but the factors that
      determine these differential effects are unknown. Here we report that the
      transcriptional corepressor BASP1 interacts with ERalpha and in breast cancer
      cells, this interaction is enhanced by tamoxifen. We find that BASP1 acts as a
      major selectivity factor in the transcriptional response of breast cancer cells
      to tamoxifen. In all, 40% of the genes that are regulated by tamoxifen in breast
      cancer cells are BASP1 dependent, including several genes that are associated
      with tamoxifen resistance. BASP1 elicits tumour-suppressor activity in breast
      cancer cells and enhances the antitumourigenic effects of tamoxifen treatment.
      Moreover, BASP1 is expressed in breast cancer tissue and is associated with
      increased patient survival. Our data have identified BASP1 as an ERalpha cofactor
      that has a central role in the transcriptional and antitumourigenic effects of
      tamoxifen.

PMID- 28492544
TI  - Halofuginone dually regulates autophagic flux through nutrient-sensing pathways
      in colorectal cancer.
AB  - Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous
      study found that halofuginone (HF) exerts anticancer activity in colorectal
      cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin
      complex 1) signaling pathway. But whether and how HF regulates autophagy and
      metabolism to inhibit cancer growth remains an open question. Here, we unveil
      that HF activates ULK1 by downregulation of its phosphorylation site at Ser757
      through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux
      under nutrient-rich condition. On the other hand, HF inactivates ULK1 by
      downregulation of its phosphorylation sites at Ser317 and Ser777 through
      LKB1/AMPK signaling pathway, resulting in autophagic inhibition under nutrient
      poor condition. Furthermore, Atg7-dependent autophagosome formation is also
      induced under nutrient-rich condition or blocked in nutrient-poor environment,
      respectively, upon HF treatment. More interestingly, we also found that HF
      inhibits glycolysis under nutrient-rich condition, whereas inhibits
      gluconeogenesis under nutrient-poor condition in an Atg7-dependent manner,
      suggesting that autophagy has a pivotal role of glucose metabolism upon HF
      treatment. Subsequent studies showed that HF treatment retarded tumor growth in
      xenograft mice fed with either standard chow diet or caloric restriction through
      dual regulation of autophagy in vivo. Together, HF has a dual role in autophagic
      modulation depending on nutritional conditions for anti-CRC.

PMID- 28492545
TI  - Chronically stressed or stress-preconditioned neurons fail to maintain stress
      granule assembly.
AB  - Dysregulation of stress granules (SGs) and their resident proteins contributes to
      pathogenesis of a number of (neuro)degenerative diseases. Phosphorylation of
      eIF2alpha is an event integrating different types of cellular stress and it is
      required for SG assembly. Phosphorylated eIF2alpha (p-eIF2alpha) is upregulated
      in the nervous system in some neurodegenerative conditions. We found that
      increasing p-eIF2alpha level by proteasomal inhibition in cultured cells,
      including mouse and human neurons, before a SG-inducing stress ('stress
      preconditioning'), limits their ability to maintain SG assembly. This is due to
      upregulation of PP1 phosphatase regulatory subunits GADD34 and/or CReP in
      preconditioned cells and early decline of p-eIF2alpha levels during subsequent
      acute stress. In two model systems with constitutively upregulated p-eIF2alpha,
      mouse embryonic fibroblasts lacking CReP and brain neurons of tau transgenic
      mice, SG formation was also impaired. Thus, neurons enduring chronic stress or
      primed by a transient mild stress fail to maintain p-eIF2alpha levels following
      subsequent acute stress, which would compromise protective function of SGs. Our
      findings provide experimental evidence on possible loss of function for SGs in
      certain neurodegenerative diseases.

PMID- 28492547
TI  - Autophagy is essential for hearing in mice.
AB  - Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells
      (HCs) are postmitotic at late-embryonic differentiation and postnatal stages, and
      their damage is the major cause of hearing loss. There is no measurable HC
      regeneration in the mammalian cochlea, and the maintenance of cell function is
      crucial for preservation of hearing. Here we generated mice deficient in
      autophagy-related 5 (Atg5), a gene essential for autophagy, in the HCs to
      investigate the effect of basal autophagy on hearing acuity. Deletion of Atg5
      resulted in HC degeneration and profound congenital hearing loss. In autophagy
      deficient HCs, polyubiquitinated proteins and p62/SQSTM1, an autophagy substrate,
      accumulated as inclusion bodies during the first postnatal week, and these
      aggregates increased in number. These findings revealed that basal autophagy has
      an important role in maintenance of HC morphology and hearing acuity.

PMID- 28492546
TI  - Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial
      DNA fragmentation and regulates macrophage cell death after trauma.
AB  - Trauma is a major cause of systemic inflammatory response syndrome and multiple
      organ dysfunction syndrome. Macrophages (Mphi) direct trauma-induced
      inflammation, and Mphi death critically influences the progression of the
      inflammatory response. In the current study, we explored an important role of
      trauma in inducing mitochondrial DNA (mtDNA) damage in Mphi and the subsequent
      regulation of Mphi death. Using an animal pseudo-fracture trauma model, we
      demonstrated that tissue damage induced NADPH oxidase activation and increased
      the release of reactive oxygen species via cold-inducible RNA-binding protein
      (CIRP)-TLR4-MyD88 signaling. This in turn, activates endonuclease G, which serves
      as an executor for the fragmentation of mtDNA in Mphi. We further showed that
      fragmented mtDNA triggered both p62-related autophagy and necroptosis in Mphi.
      However, autophagy activation also suppressed Mphi necroptosis and pro
      inflammatory responses. This study demonstrates a previously unidentified
      intracellular regulation of Mphi homeostasis in response to trauma.

PMID- 28492548
TI  - Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast
      epithelial cells.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin
      signaling pathways and inhibitors against PTP1B are being developed as promising
      drug candidates for treatment of obesity. PTP1B has also been linked to breast
      cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been
      shown to be a regulator of cell adhesion and migration in normal and cancer
      cells. In this study, we analyzed the PTP1B expression in normal breast tissue,
      primary breast cells and the breast epithelial cell line D492. In normal breast
      tissue and primary breast cells, PTP1B is widely expressed in both epithelial and
      stromal cells, with highest expression in myoepithelial cells and fibroblasts.
      PTP1B is widely expressed in branching structures generated by D492 when cultured
      in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and
      another mammary epithelial cell line HMLE resulted in reduced cell proliferation
      and induction of anoikis. These changes were seen when cells were cultured both
      in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression
      of cell adhesion proteins and actin polymerization. Moreover, epithelial to
      mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal
      sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B
      inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using
      miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In
      conclusion, we have shown that PTP1B is widely expressed in the human breast
      gland with highest expression in myoepithelial cells and fibroblasts. Inhibition
      of PTP1B in D492 and HMLE affects cell-cell adhesion and induces anoikis-like
      effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B
      inhibitors making PTP1B a potential candidate for further studies as a target for
      drug development in cancer involving the EMT phenotype.

PMID- 28492549
TI  - Enhanced neuroprotective efficacy of bone marrow mesenchymal stem cells co
      overexpressing BDNF and VEGF in a rat model of cardiac arrest-induced global
      cerebral ischemia.
AB  - Cardiac arrest-induced global cerebral ischemia injury (CA-GCII) usually leads to
      a poor neurological outcome without an effective treatment. Bone marrow-derived
      mesenchymal stem cells (BMMSCs) may provide a potential cell-based therapy
      against neurologic disorders through induction of brain-derived neurotrophic
      factor (BDNF) and vascular endothelial growth factor (VEGF). To optimize the
      neuroprotective efficacy of BMMSCs further, in this study we have derived BMMSCs,
      which co-overexpress both BDNF and VEGF, and tested them for the treatment of CA
      GCII in a rat model. Lentiviruses that express rat BDNF exon IV or VEGF-A were
      created using the bicistronic shuttle vectors of pLVX-IRES-ZsGreen1 and pLVX-IRES
      tdTomato, respectively. BMMSCs that were co-transduced with the engineered
      lentiviruses with co-overexpression of both BDNF and VEGF along with
      corresponding fluorescent protein reporters were injected via jugular vein of
      rats that just recovered from a cardiac arrest. Animals were then scored for
      neurofunctional deficits and examined for brain pathology and gene expression
      relevant to the engraftment seven days after the treatments. We demonstrate that
      anchorage of lentiviral vector-transduced BMMSCs, which co-overexpressed both
      BDNF and VEGF in the hippocampus and temporal cortex along with significantly
      ameliorated brain pathology and improved neurofunctional performance in CA-GCII
      rats after transplantation. These findings provide a proof of concept for the
      further validation of engineered BMMSCs for the treatment of CA-GCII patients in
      clinical practice in the future.

PMID- 28492550
TI  - TXNIP regulates mitophagy in retinal Muller cells under high-glucose conditions:
      implications for diabetic retinopathy.
AB  - Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and
      apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of
      damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains
      unexplored. Here we investigate the associated cellular and molecular mechanisms
      underlying mitophagy in retinal cells under diabetic conditions. For this, we
      maintained a rat Muller cell line (rMC1) under high-glucose (25 mM, HG) or low
      glucose (5.5 mM, LG) condition for 5 days. Our data reveal that HG upregulates
      TXNIP in the cytosol as well as in the MT. Moreover, mitochondrial oxidative
      stress and membrane depolarization occur under prolonged hyperglycemia leading to
      fragmentation. These damaged MT are targeted to lysosome for mitophagic
      degradation, as is evident by co-localization of mitochondrial protein COXIV, a
      subunit of cytochrome c oxidase, with autophagosome marker LC3BII and the
      lysosomal membrane protein LAMP2A. In addition, under HG conditions, there is an
      accumulation of dynamin-related fission protein Drp1 and E3 ubiquitin ligase
      Parkin in damaged MT, suggesting their roles in mitochondrial fragmentation and
      ubiquitination, respectively, which is absent in LG conditions. Subsequently,
      ubiquitin receptors, optineurin and p62/sequestrome 1, bind to the damaged MT and
      target them to LC3BII autophagosomes. Conversely, TXNIP knockout via CRISPR/Cas9
      and TXNIP gRNA prevents the HG-induced mitochondrial damage and mitophagy in
      rMC1. Last, TXNIP level is also significantly upregulated in the diabetic rat
      retina in vivo and induces radial glial fibrillary acidic protein expression, a
      marker for Muller glia activation, and the formation of LC3BII puncta, which are
      prevented by intravitreal injection of TXNIP siRNA. Therefore, TXNIP represents a
      potential target for preventing ocular complications of diabetes.

PMID- 28492552
TI  - All-trans retinoic acid and arsenic trioxide fail to derepress the monocytic
      differentiation driver Irf8 in acute promyelocytic leukemia cells.
AB  - All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads
      to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL)
      cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha
      (PML/RARalpha). Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based
      therapies, and a potential failure of ATRA and ATO in completely reversing
      PML/RARalpha-driven oncogenic alterations has not been comprehensively examined.
      Here we characterized the in vivo primary responses of dysregulated genes in APL
      cells treated with ATRA and ATO using a GFP-labeled APL model. Although induced
      granulocytic differentiation of APL cells was evident after ATRA or ATO
      administration, the expression of the majority of dysregulated genes in the c
      Kit+ APL progenitors was not consistently corrected. Irf8, whose expression
      increased along with spontaneous differentiation of the APL progenitors in vivo,
      represented such a PML/RARalpha-dysregulated gene that was refractory to ATRA/ATO
      signaling. Interestingly, Irf8 induction, but not its knockdown, decreased APL
      leukemogenic potential through driving monocytic maturation. Thus, we reveal that
      certain PML/RARalpha-dysregulated genes that are refractory to ATRA/ATO signaling
      are potentially crucial regulators of the immature status and leukemogenic
      potential of APL cells, which can be exploited for the development of new
      therapeutic strategies for ATRA/ATO-resistant APL cases.

PMID- 28492551
TI  - Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a
      mouse model of neonatal hypoxia-ischemia.
AB  - Mitochondria contribute to neonatal hypoxic-ischemic brain injury by releasing
      potentially toxic proteins into the cytosol. CHCHD4 is a mitochondrial
      intermembrane space protein that plays a major role in the import of
      intermembrane proteins and physically interacts with apoptosis-inducing factor
      (AIF). The purpose of this study was to investigate the impact of CHCHD4
      haploinsufficiency on mitochondrial function and brain injury after cerebral
      hypoxia-ischemia (HI) in neonatal mice. CHCHD4+/- and wild-type littermate mouse
      pups were subjected to unilateral cerebral HI on postnatal day 9. CHCHD4
      haploinsufficiency reduced insult-related AIF and superoxide dismutase 2 release
      from the mitochondria and reduced neuronal cell death. The total brain injury
      volume was reduced by 21.5% at 3 days and by 31.3% at 4 weeks after HI in
      CHCHD4+/- mice. However, CHCHD4 haploinsufficiency had no influence on
      mitochondrial biogenesis, fusion, or fission; neural stem cell proliferation; or
      neural progenitor cell differentiation. There were no significant changes in the
      expression or distribution of p53 protein or p53 pathway-related genes under
      physiological conditions or after HI. These results suggest that CHCHD4
      haploinsufficiency afforded persistent neuroprotection related to reduced release
      of mitochondrial intermembrane space proteins. The CHCHD4-dependent import
      pathway might thus be a potential therapeutic target for preventing or treating
      neonatal brain injury.

PMID- 28492553
TI  - A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem
      cell development during Xenopus intestinal metamorphosis.
AB  - The Myc/Mad/Max network has long been shown to be an important factor in
      regulating cell proliferation, death and differentiation in diverse cell types.
      In general, Myc-Max heterodimers activate target gene expression to promote cell
      proliferation, although excess of c-Myc can also induce apoptosis. In contrast,
      Mad competes against Myc to form Mad-Max heterodimers that bind to the same
      target genes to repress their expression and promote differentiation. The role of
      the Myc/Mad/Max network during vertebrate development, especially, the so-called
      postembryonic development, a period around birth in mammals, is unclear. Using
      thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here
      that Mad1 is induced by T3 in the intestine during metamorphosis when larval
      epithelial cell death and adult epithelial stem cell development take place. More
      importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing
      apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells
      during intestinal metamorphosis, suggesting that Mad1 may have a role in cell
      death during development. By using transcription activator-like effector nuclease
      mediated gene-editing technology, we have generated Mad1 knockout Xenopus
      animals. This has revealed that Mad1 is not essential for embryogenesis or
      metamorphosis. On the other hand, consistent with its spatiotemporal expression
      profile, Mad1 knockout leads to reduced larval epithelial apoptosis but
      surprisingly also results in increased adult stem cell proliferation. These
      findings not only reveal a novel role of Mad1 in regulating developmental cell
      death but also suggest that a balance of Mad and Myc controls cell fate
      determination during adult organ development.

PMID- 28492554
TI  - The novel long intergenic noncoding RNA UCC promotes colorectal cancer
      progression by sponging miR-143.
AB  - The human genome contains thousands of long intergenic noncoding RNAs (lincRNAs).
      However, the functional roles of these transcripts and the mechanisms responsible
      for their deregulation in colorectal cancer (CRC) remain elusive. A novel lincRNA
      termed upregulated in CRC (UCC) was found to be highly expressed in human CRC
      tissues and cell lines. UCC levels correlated with lymph node metastasis, Dukes'
      stage, and patient outcomes. In SW480 and SW620 cells, knockdown of UCC inhibited
      proliferation, invasion, and cell cycle progression and induced apoptosis in
      vitro. Xenograft tumors grown from UCC-silenced SW620 cells had smaller mean
      volumes and formed more slowly than xenograft tumors grown from control cells.
      Inversely, overexpression of UCC in HCT116 promoted cell growth and invasion in
      vitro. Bioinformatics analysis, dual-luciferase reporter assays, and RNA
      immunoprecipitation assays showed that miR-143 can interact with UCC, and we
      found that UCC expression inversely correlates with miR-143 expression in CRC
      specimens. Moreover, mechanistic investigations showed that UCC may act as an
      endogenous sponge by competing for miR-143, thereby regulating the targets of
      this miRNA. Our results suggest that UCC and miR-143 may be promising molecular
      targets for CRC therapy.

PMID- 28492555
TI  - Acidic pH is essential for maintaining mast cell secretory granule homeostasis.
AB  - It has been recognized for a long time that the secretory granules of mast cells
      are acidic, but the functional importance of maintaining an acidic pH in the mast
      cell granules is not fully understood. Here we addressed this issue by examining
      the effects of raising the pH of the mast cell secretory granules. Mast cells
      were incubated with bafilomycin A1, an inhibitor of the vacuolar-type ATPase
      proton pump. Supporting a role of vacuolar-type ATPase in mast cell granule
      acidification, bafilomycin A1 treatment caused a robust increase in granule pH.
      This was accompanied by marked effects on mast cell granules, including swelling
      and acquisition of vacuole-like morphology. Moreover, bafilomycin A1 caused
      extensive, yet selective effects on the granule content. These included aberrant
      processing of pro-carboxypeptidase A3 and a reduction in the level of
      intracellular histamine, the latter being accompanied by an increase in
      extracellular histamine. In contrast, the storage of beta-hexosaminidase, a
      prototype lysosomal hydrolase known to be stored in mast cell granules, was not
      affected by abrogation of granule acidification. Moreover, bafilomycin A1 caused
      a reduction of tryptase enzymatic activity and appearance of tryptase degradation
      products. Tryptase inhibition prevented the formation of such degradation
      products, suggesting that the pH elevation causes tryptase to undergo
      autoproteolysis. Taken together, our findings reveal that mast cell secretory
      granule homeostasis is critically dependent on an acidic milieu.

PMID- 28492556
TI  - PLSCR1/IP3R1/Ca2+ axis contributes to differentiation of primary AML cells
      induced by wogonoside.
AB  - Multiple lines of evidence have demonstrated that increased expression of
      phospholipid scramblase 1 (PLSCR1) is involved in the differentiation of acute
      myeloid leukemia (AML) cells by several differentiation-inducing agents including
      ATRA and phorbol 12-myristate 13-acetate. However, none of these agents can
      achieve nonhomogenous subcellular distribution of PLSCR1. We have demonstrated
      that wogonoside possesses differentiation and anti-leukemic effects in AML cell
      lines by promoting PLSCR1 trafficking into nucleus. Here we report that
      wogonoside promotes the expression of PLSCR1 and enhances its nuclear
      translocation and binding to the 1, 4, 5-trisphosphate receptor 1 (IP3R1)
      promoter in AML patient-derived primary cells. Wogonoside activates IP3R1, in
      turn, promotes release of Ca2+ from endoplasmic reticulum, and eventually leads
      to cell differentiation. Our in vivo study further confirms that wogonoside can
      promote PLSCR1 and IP3R1 expression in primary AML cells and reduce the AML cell
      counts in engrafted nonobese diabetic/severe combined immunodeficient mice. Taken
      together, our findings provide new insight into the mechanism of wogonoside
      induced differentiation and anti-leukemic effect on primary AML cells, suggesting
      the therapeutic potential of wogonoside for AML, especially for non-APL AML.

PMID- 28492557
TI  - Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo
      through SHP-2-dependent inhibition of STAT3 activation.
AB  - Malignant gliomas (MGs) are one of the most common primary brain cancers in
      adults with a high mortality rate and relapse rate. Thus, finding better
      effective approaches to treat MGs has become very urgent. Here, we studied the
      effects of cryptotanshinone (CTS) on MGs in vitro and in vivo, and explored the
      underlying mechanisms. Effects of CTS in vitro on cell proliferation, cycle,
      migration and invasion were evaluated. The activation of JAK/STATs signaling was
      detected by western blot and immunofluorescenc staining. SHP-2 inhibitor or SiRNA
      were used to determine the involvement of SHP-2. The in vivo anti-MGs activity of
      CTS was studied with nude mice bearing intracerebral U87 xenografts. Our results
      revealed that CTS significantly inhibited the proliferation of MGs in vitro via
      inhibiting STAT3 signal pathway. The cell cycle was arrested at G0/G1 phase.
      Although CTS did not change the expression of total SHP-2 protein, the tyrosine
      phosphatase activity of SHP-2 protein was increased by CTS treatment in a dose
      dependent manner in vivo and in vitro. SHP-2 inhibitor or SiRNA could reverse the
      inhibitory effect of CTS on phosphorylation of STAT3 Tyr705. In vivo study also
      showed that CTS inhibited the intracranial tumor growth and extended survival of
      nude mice bearing intracerebral U87 xenografts, confirming an inhibitory effect
      of CTS on MGs. Our results indicated CTS may be a potential therapeutic agent for
      MGs. The inhibitory action of CTS is largely attributed to the inhibition of
      STAT3 Tyr705 phosphorylation with a novel mechanism of upregulating the tyrosine
      phosphatase activity of SHP-2 protein.

PMID- 28492558
TI  - Harnessing combined p19Arf and interferon-beta gene transfer as an inducer of
      immunogenic cell death and mediator of cancer immunotherapy.

PMID- 28492559
TI  - MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by
      inhibiting the AKT/mTOR pathway.
AB  - Despite the development of promising cancer therapeutic drugs, multiple myeloma
      (MM) remains an incurable disease. Bufalin is a bufanolide steroid compound of
      the traditional Chinese medicine Chan Su that was previously shown to exert
      growth suppression effects on myeloma cell lines. Previous studies conducted by
      our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma
      cells, which is considered an essential pathway to disease progression and is
      related to drug resistance in MM. In view of the significant role of AKT in MM,
      the allosteric AKT inhibitor MK2206 was selected in order to enhance the
      antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and
      RPMI8226). The data indicated that MK2206 enhanced the cytotoxicity of bufalin in
      MM cells, via the suppression of cellular proliferation and the induction of
      apoptosis, as demonstrated by cleavage of apoptosis-related proteins. This effect
      was further noted in the presence of exogenous interleukin-6 and/or following the
      co-culture of MM cells with bone marrow stromal cells (BMSC). This process was
      associated with the inhibition of the AKT/mTOR pathway. The combination of
      bufalin with MK2206 reduced the secretion of IL-6 in U266 cells. The combined
      treatment exhibited similar anti-MM effects in bortezomib-resistant cell lines
      (NCI-H929R, U266R). In addition to the in vitro cell line models, the synergistic
      effect was noted in primary MM cells and in MM xenografts of BALB-c and NOD-SCID
      mice. In conclusion, the data suggested that MK2206 significantly enhanced the
      cytocidal effects of bufalin in MM cells, regardless of the sensitivity to
      bortezomib, via the inhibition of the AKT/mTOR pathway. The study provided the
      basis of a promising treatment approach for MM.

PMID- 28492561
TI  - [Sacubitril/valsartan, a new and effective treatment for heart failure with
      reduced ejection fraction].
AB  - Despite significant therapeutic advances, patients with chronic heart failure and
      reduced ejection fraction (HFrEF) remain at high risk for heart failure
      progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF,
      has shown improved cardiovascular outcomes with sacubitril/valsartan
      (Entresto(r), Novartis), previously known as LCZ696, compared with angiotensin
      converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for
      heart failure treatment. Sacubitril/valsartan represents a first-in-class drug
      acting through inhibition of angiotensin receptor and neprilysin, thus modulating
      the renin-angiotensin-aldosterone system and vasoactive substances such as
      natriuretic peptides. This approach can be considered a "paradigm shift" from
      neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF
      results, the European Society of Cardiology and the American Heart
      Association/American College of Cardiology guidelines proposed a substitution of
      ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on"
      strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in
      cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are
      many questions that arise spontaneously from this trial, three recognized experts
      can help us to answer them.

PMID- 28492560
TI  - miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in
      gallbladder cancer.
AB  - Gallbladder cancer (GBC) is one of the most common malignancy of the biliary
      tract characterized by its high chemoresistant tendency. Although great
      progresses have been made in recent decades for treating many cancers with
      anticancer drugs, effective therapeutics methods for anti-GBC are still lacking.
      Therefore, investigations into identifying the mechanisms underlying the drug
      resistance of GBC are greatly needed. In this study, we show that miR-218-5p
      plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were
      significantly lower in GBC than adjacent non-cancer tissues, and which were also
      associated with patient prognosis. While miR-218-5p overexpression abrogated
      gemcitabine resistance of GBC cells, silencing of which exhibited the opposite
      effects. Via six microRNA targets prediction algorithms, we found that PRKCE is a
      potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the
      luciferase activity of reporter constructs containing 3'-UTR of PRKCE and also
      reduced PRKCE expression. Further studies revealed that miR-218-5p promotes
      sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of MDR1/P-gp.
      Taken together, our results imply that an intimate correlation between miR-218-5p
      and PRKCE/MDR1 axis abnormal expression is a key determinant of gemcitabine
      tolerance, and suggest a novel miR-218-5p-based clinical intervention target for
      GBC patients.

PMID- 28492563
TI  - [Follow-up strategies after percutaneous coronary intervention: prognostic
      stratification and multidisciplinary management based on patient risk profile].
AB  - The number of percutaneous coronary interventions (PCI) is increasing worldwide.
      Follow-up strategies after PCI are extremely heterogeneous and can greatly affect
      the cost of medical care. In the present paper, practical advises are provided
      with respect to a tailored follow-up strategy on the basis of patients' risk
      profile. Clinical and interventional cardiologists, cardiac rehabilitators, and
      general practitioners equally contributed to the creation of the present document
      and defined three follow-up strategies and types and timing of clinical and
      instrumental evaluations in post-PCI patients.

PMID- 28492564
TI  - [Heart rate as a therapeutic target after acute coronary syndrome and in chronic
      coronary heart disease].
AB  - For patients with stable coronary artery disease (SCAD), either after
      hospitalization for acute cardiac events or in the chronic phase, comprehensive
      treatment programs should be devoted to: (i) reducing mortality and major adverse
      cardiovascular events, (ii) reducing the ischemic burden and related symptoms,
      and (iii) increasing exercise capacity and quality of life.Heart rate (HR) has
      demonstrated to have prognostic value and patients beyond the limit of 70 bpm
      display increased risk of all the above adverse outcomes, even after adjustment
      for parameters such as the extension of myocardial infarction and the presence of
      heart failure. It is well known that a sustained HR elevation may contribute to
      the pathogenesis of SCAD, being the likelihood of developing ischemia, plaque
      instability, trigger for arrhythmias, increased vascular oxidative stress, and
      endothelial dysfunction the mechanisms resulting in this effect. Moreover, high
      HR could promote chronotropic incompetence, leading to functional disability and
      reduced quality of life.Despite the strong relationship between HR and prognosis,
      there is heterogeneity among current guidelines in considering HR as a formal
      therapeutic target for secondary prevention in SCAD, as far as the cut-off limit.
      This expert opinion document considered major trials and observational registries
      in the modern treatment era with beta-blockers and ivabradine, suggesting that an
      adequate HR control could represent a target for (i), (ii), and (iii) therapeutic
      goals in SCAD patients with systolic dysfunction (with major evidence for reduced
      left ventricular ejection fraction <40%), and a target for (ii) and (iii) goals
      in SCAD patients with preserved left ventricular ejection fraction. The defined
      cut-off limit is 70 bpm. To date, there is room for improvement of HR control,
      since in contemporary SCAD patients HR values <70 bpm are present in less than
      half of cases, even in the vulnerable phase after an acute coronary syndrome.

PMID- 28492565
TI  - ?

PMID- 28492566
TI  - [Speckle tracking echocardiography: a practical guide].
AB  - Speckle tracking echocardiography (STE) has recently emerged as a quantitative
      technique to accurately estimate myocardial function. By the analysis of the
      motion of speckles in the two-dimensional ultrasonic image, this technique allows
      a non-Doppler angle-independent objective analysis of myocardial deformation,
      with the possibility to quantify thickening, shortening and rotation dynamics of
      cardiac function. Since this technique does not require Doppler imaging, the
      analysis is relatively angle-independent and is marginally affected by cardiac in
      plane motion artifacts. Data regarding feasibility, reproducibility and
      diagnostic accuracy appear to be optimal in several clinical contexts. This
      review describes the fundamental concepts of deformation imaging, explains how to
      obtain myocardial deformation measurements in clinical practice and highlights
      current clinical applications of STE. In addition, in relation with the recent
      extension of STE to three-dimensional echocardiography with the potential for a
      more comprehensive analysis of global and segmental myocardial function, a window
      is also opened on the perspectives of three-dimensional STE.

PMID- 28492567
TI  - [Echocardiographic assessment of mitral regurgitation in the perspective of valve
      repair].
AB  - Echocardiography is the most used imaging technique for the study of patients
      with mitral regurgitation because of its wide distribution, non-invasiveness and
      ability to provide diagnostic, functional, hemodynamic and prognostic
      evaluations. Also, echocardiography can provide essential information on surgical
      and percutaneous reparability of the regurgitant valve and can guide the surgical
      and interventional indications relative to valve repair. However, the
      echocardiographic study is not always appropriately performed in clinical
      practice and based on a surgery perspective. Therefore, the purpose of this
      article is to describe how to best use echocardiography for evaluation of
      patients with mitral regurgitation, highlighting the advantages and limitations
      of this technique before and after surgical or interventional repair.

PMID- 28492569
TI  - [Electromagnetic interference in the current era of cardiac implantable
      electronic devices designed for magnetic resonance environment].
AB  - In the last decades we are observing a continuous increase in the number of
      patients wearing cardiac implantable electronic devices (CIEDs). At the same
      time, we face daily with a domestic and public environment featured more and more
      by the presence and the utilization of new emitters and finally, more medical
      procedures are based on electromagnetic fields as well. Therefore, the topic of
      the interaction of devices with electromagnetic interference (EMI) is
      increasingly a real and actual problem.In the medical environment most attention
      is paid to magnetic resonance, nevertheless the risk of interaction is present
      also with ionizing radiation, electrical nerve stimulation and electrosurgery. In
      the non-medical environment, most studies reported in the literature focused on
      mobile phones, metal detectors, as well as on headphones or digital players as
      potential EMI sources, but many other instruments and tools may be intentional or
      non-intentional sources of electromagnetic fields.CIED manufacturers are more and
      more focusing on new technological features in order to make implantable devices
      less susceptible to EMI. However, patients and emitter manufacturers should be
      aware that limitations exist and that there is not complete immunity to EMI.

PMID- 28492568
TI  - [Cardiac tumors: role of magnetic resonance imaging].
AB  - The incidental finding of a cardiac or paracardiac mass constitutes for
      cardiologists a relevant diagnostic and therapeutic problem. In fact, although
      primary cardiac tumors are infrequently, metastases, as well as non-neoplastic
      masses and pseudomasses, are much more frequent. A key role is played by
      echocardiography, but the latter is not always nullifying. Sometimes even the
      currently used imaging techniques may be limited in oncology. Cardiac magnetic
      resonance (CMR) is a multi-parametric technique of imaging considered nowadays
      the gold standard for non-invasive soft tissue characterization. CMR allows (i)
      to better evaluate the relationship between the tumor and adjacent structures,
      (ii) to detect the degree of infiltration or the expansion of the mass in the
      pericardium, and (iii) to predict the possible malignancy of a mass with a higher
      accuracy than other methods. In addition, CMR can favor the choice of the
      technique for surgical resection by providing information regarding cardiac
      function and the possible hemodynamic impairment. In this regard, we here present
      a narrative review on the most frequent cardiac manifestations of tumors, masses
      and pseudomasses, as well as the currently used CMR techniques in this setting.

PMID- 28492570
TI  - [The use of mechanical chest compression devices for both out-of-hospital and in
      hospital refractory cardiac arrest].
AB  - The purpose of cardiopulmonary resuscitation after sudden cardiac arrest is to
      restore minimal blood flow to provide oxygen to the brain and other vital organs.
      Chest compressions and external defibrillation are the first line for circulatory
      support. Although early defibrillation is the main factor influencing survival,
      cardiopulmonary resuscitation must be characterized by high-quality external
      chest compressions. Unfortunately, the performance of manual chest compressions
      decreases during time and in hostile conditions. For these reasons, mechanical
      devices for chest compression are able to support rescuers during cardiopulmonary
      resuscitation. Commonly used mechanical chest compression devices in Europe
      include LUCAS and Autopulse. Routine utilization of mechanical chest compression
      devices cannot be recommended because randomized controlled trials, such as LINC
      and PARAMEDIC for LUCAS and CIRC for Autopulse, have not demonstrated their
      superiority compared with manual chest compressions. The aim of this review is to
      analyze recent data regarding utilization of mechanical chest compression
      devices, and to clarify advantages and limitations.

PMID- 28492571
TI  - [Teamwork for cardiac imaging: coronary computed tomography angiography and low
      dose radiation exposure: a cardiology center experience].
AB  - BACKGROUND: Multidetector coronary computed tomography angiography (CCTA) is
      increasingly used for noninvasive imaging of the coronary arteries. Radiation
      exposure, however, is a potential limitation to a more extensive use of this
      imaging modality. We aimed to demonstrate that a professional teamwork approach,
      including a cardiologist and a radiologist in performing CCTA, may allow to
      obtain best quality exams with very low radiation doses. METHODS: A total of 998
      consecutive patients underwent CCTA in accordance with the most recent
      guidelines. The following procedures were undertaken to reduce the radiation
      dose: (a) preliminary cardiological evaluation to check for CCTA eligibility; (b)
      optimized heart rate control with beta-blockers and/or ivabradine; and (c) the
      use of nonstandardized computed tomography protocols and algorithms for dose
      reduction. RESULTS: All the patients underwent a preliminary cardiological
      evaluation; 89% of them were pretreated with oral or intravenous beta-blockers
      and/or ivabradine; 806 patients (81%) were scanned by means of prospective
      gating, which allowed a radiation dose exposure of 161 +/- 68.64 mGy; 192
      patients (19%) underwent a retrospective gating protocol, with a radiation dose
      exposure of 1135.15 +/- 485.87 mGy. In 13 patients (1%) CCTA was uninterpretable
      because of artifacts. Exam quality was not affected by the use of low-dose
      computed tomography scanning. Coronary calcium score and/or left ventricular
      functional analysis were never performed. CONCLUSIONS: The preliminary selection
      and preparation of patients and optimized scanner utilization allow a substantial
      reduction in radiation dose for most of the patients submitted to CCTA without
      affecting image quality. In our experience, a team approach was necessary to
      allow a "low-dose learning curve" and a progressive reduction in radiation doses
      administered to patients by means of the prospective gating protocol.

PMID- 28492572
TI  - [The spiral of evil: iatrogenic coronary and aortic dissection].
AB  - Iatrogenic coronary and aortic dissection is one of the worst complication during
      a percutaneous coronary intervention. Nevertheless, it can be approached and
      effectively resolved by a percutaneous way, sealing the false lumen "entry door"
      with a covered stent, even if this device is more thrombogenic than other bare
      metal or drug-eluting stents. We report the case of a 60-year-old man with acute
      ST-elevation myocardial infarction complicated by both iatrogenic dissection and
      multiple stent thrombosis.

PMID- 28492573
TI  - [Lotus Sadra valve implantation complicated by type B aortic dissection:
      diagnosis and treatment].
AB  - Transcatheter aortic valve implantation (TAVI) is a validated technique for the
      treatment of aortic valve stenosis in patients with high surgical risk or
      inoperable. We present the case of an 80-year-old woman with severe aortic valve
      stenosis (mean gradient 55 mmHg), mild surgical risk, who refused traditional
      surgery. We implanted a Lotus Sadra 25 mm (Boston Scientific, Marlborough, MA,
      USA) via the transfemoral route. During pull back delivery, the patient
      experienced interscapular pain with angiographic evidence of type B aortic
      dissection effectively treated by implanting a vascular endoprosthesis Valiant 30
      x 150 mm (Medtronic Vascular, Santa Rosa, CA, USA). Type B aortic dissection is a
      rare event during TAVI. The onset of procedural complications, often
      unpredictable, suggests the need for more extensive knowledge of materials and
      techniques, in particular with respect to endovascular treatment of the aortic
      and iliac-femoral district.

PMID- 28492574
TI  - [Magnetic resonance detection of direct ascending aorta invasion by lung cancer].

PMID- 28492575
TI  - Alterations of cerebral white matter structure in psychosis and their clinical
      correlations: a systematic review of Diffusion TensorImaging studies.
AB  - Schizophrenia is a common, severe and chronically disabling mental illness. Most
      of MRI studies in schizophrenia suggest theinvolvement of white matter (WM)
      pathology in multiple cerebral regions in the neurobiology of this condition.
      White matter fiber tracts connecting numerous cortical regions have been the
      focus of a number of studies using a magnetic resonance technique called
      "Diffusion Tensor Imaging" (DTI). A literature search of published DTI studies
      was conducted using the major database National Centre for Biotechnology
      information (NCBI) PubMed (MEDLINE). Our review covers 95 published papers. We
      summarise the main DTI findings involving the different brain regions in patients
      affected by or at high-risk for psychosis; we discuss clinical implications of
      these white matter disruptions and the limitations of current studies, listing
      the potential confounds and suggesting potential future research directions.

PMID- 28492576
TI  - [Mental capacity and capacity to consent: multicentric study in a involuntary
      psychiatric hospitalized patients sample].
AB  - BACKGROUND: The purpose of this longitudinal observational study is to evaluate
      the course and impact of clinical, social, and behavioral variables on the
      involuntary readmission of psychiatric patients, during a 6-months follow-up
      after discharge from a prior involuntary hospitalization. METHODS: N=131
      involuntarily committed psychiatric patients were enrolled in three university
      hospitals (Bari n=57; Perugia n=42; Rome n=32). At the first assessment cognitive
      functioning (MMSE), psychiatric symptoms severity (BPRS-E), capacity to consent
      to treatment (MacCAT-T) as well as principal socio-demographic and clinical
      variables were collected. At 6-months follow-up, we collected data concerning
      involuntary psychiatric readmissions, pharmacotherapy adherence, new deliberate
      self-harm or harm to others as well as having been legally prosecuted. RESULTS:
      N=120 patients were reevaluated at follow-up (M=188 days, SD=12.6); among these
      n=15 (12.5%) have had a new involuntary psychiatric admission due to an acute
      mental disorder. Re-hospitalized patients showed higher rates of harm to others
      (p<0.05) and legal prosecution (p<0.05); there was moreover a trend toward higher
      pharmacological dropout rates in involuntarily rehospitalized patients. We found
      no differences between the two groups in baseline psychiatric symptoms severity
      and cognitive functioning, whereas involuntary re-hospitalization was associated
      with more frequent involuntary hospitalization during last year (p<0.05) and
      higher MacCAT-T reasoning (p<0.05). CONCLUSIONS: Involuntary psychiatric
      readmission rates proved to be poorly associated with clinical features assessed
      during previous hospitalization. Our data suggest that social and legal factors,
      including those connected to patients' dangerousness, could play a role also in a
      civil commitment system based solely on the need for treatment.

PMID- 28492577
TI  - [Neuropsychological profiles, personality features and familial relational
      patterns in parents of children with Autism Spectrum Disorders].
AB  - INTRODUCTION: The study of neuropsychological profiles and personality features
      of parents of persons with Autism Spectrum Disorder (ASD) has highlighted
      specific traits that turned out to be useful for diagnostic purposes. AIM AND
      METHODS: In our study, psychodiagnostic measures have been used to investigate
      cognitive profiles, personality features and familial relational patters in a
      group of parents of children with ASD associated to Intellectual Disability (ID).
      This group was then compared with a another group of parents of children with
      Prader-Willi syndrome. RESULTS: Results show no differences between the two
      groups with regard to Intellectual Quotient, while significant differences were
      found at the intelligence test Wechsler, which partially confirmed data from the
      literature relating to the performances of parents of persons with ASD. No
      differences were found in the executive functioning and memory abilities. As for
      familial relational patters, families of children with ASD showed decreased
      cohesion and higher disengagement. DISCUSSION AND CONCLUSIONS: Results obtained
      in the domains of familial relational patterns and emotional personality
      components seem to confirm how children's disability can significantly impact on
      the entire household, in particular in the case of children with ASD. This data
      suggest the need for intervention programs aimed at supporting the entire
      household, with the objective of improving coping strategies and resilience
      resources of the family.

PMID- 28492578
TI  - Implicit affectivity in patients with borderline personality disorder.
AB  - AIMS: It has been argued that borderline personality disorder (BPD) is related to
      an enhanced affective reactivity. According to findings from research based on
      self-report, individuals with BPD develop and feel more negative and less
      positive affect than healthy individuals. Implicit affectivity, which can be
      measured using indirect assessment methods, relates to processes of the
      impulsive, intuitive system. In the present study, implicit and explicit
      affectivity was examined in patients suffering from BPD compared to healthy
      persons. MATERIALS AND METHODS: Thirty-five women with BPD and 35 healthy women
      participated in the study. Implicit affectivity was assessed using the Implicit
      Positive and Negative Affect Test (IPANAT). Measures of explicit state and trait
      affectivity were also administered. RESULTS: BPD women had lower explicit
      positive state and trait affect scores and higher negative state and trait affect
      scores than healthy women. They had also lower implicit positive affect but they
      did not differ from healthy women regarding implicit negative affect. Total
      number of comorbiddisorders was correlated with both implicit positive and
      implicit negative affect. DISCUSSION AND CONCLUSIONS: According to our data, BPD
      patients exhibit reduced implicit positive affect as well as reduced explicit
      positive affect compared to healthy persons. According to our IPANAT data, BPD
      patients are characterized by a normal disposition to develop negative affective
      reactions which is in line with a number of findings from psycho-physiological
      research on BPD. Self-reports of negative affectivity in BPD could be biased by
      negative distortion.

PMID- 28492579
TI  - Prevalence and factors associated with problematic internet use: an Italian
      survey among L'Aquila students.
AB  - AIM: In this study we examined the prevalence of internet addiction (IA) and its
      associated factors in a sample of Italian students. MATERIALS AND METHODS: This
      is an observational study that involved 1403 students aged 15-24 and conducted in
      L'Aquila, Italy. 1129 students accepted to participate in our study and completed
      the Internet Addiction Test: 41% were male and the mean age of total sample was
      19+/-2.8 years. RESULTS: The prevalence of "average user" was 51% (95% CI: 48
      54). The prevalence of "problematic user" was 23% (95% CI: 21-26). Among the
      students with a problematic use, 8 were addicted, the 0.7% in the whole sample.
      There was a significant age difference (p=0.029), but no gender difference
      (p=0.311) between "average users" and "problematic users". The association of
      internet use and educational level (School or University) was not significant
      (p=0.704). DISCUSSION: Our results showed that about one student out of 100 had
      an IA. Gender and educational level were not significantly associated with IA.
      Instead, we found a strong association with age: there was not a decrease of
      internet use during a lifetime, with negative consequences on quality of life.
      CONCLUSION: Our study reported a percentage of 30% of problematic internet use
      among students. These findings suggest the importance of early detection among
      youth and of structured interventions that should be carried out to prevent
      abnormal global life functioning.

PMID- 28492583
TI  - [Adherence to long-term therapies and its relevance to epidemiology.]
AB  - In Italy, 40% of the population is affected by chronic pathologies, like
      diabetes, chronic obstructive pulmonary disease (COPD) or heart failure. Chronic
      diseases are the leading cause of mortality in the world. Although long-term
      medications are effective, approximately 50% of patients do not take their
      medications as prescribed. The lack of medication adherence is associated with an
      increased risk of hospitalization and death. According to recent research, the
      low adherence to treatment is a multidimensional problem determined by the
      interaction of patient-related factors, physician-related factors and health
      system-related factors. In a study of about 10,000 patients, after a hospital
      discharge for myocardial infarction, only 63% of patients were adherent to poly
      therapy in the following two years. The probability of adherence was influenced
      by disease severity, therapy-related factors, patient's age and comorbidities,
      post-hospital follow-up visits, and network organizational forms in primary care.
      Moreover, a relevant variation in adherence to treatment was observed among
      health care providers. This heterogeneity raises equity concerns in access to
      optimal care.

PMID- 28492584
TI  - [Community pharmacy; towards a new model.]
AB  - In recent years, even in Italy, a new model of "Community pharmacy" is being
      developed, which identifies the pharmacist as the most accessible health care
      professional for citizens, and recognizes his role in preventing chronic
      diseases. A project started in Piedmont (Italy) in 2012 has aimed at applying and
      evaluating this model of pharmacy in the prevention of diabetes, through the
      early detection of individuals with undiagnosed diabetes or at high risk of
      developing the disease, or with counselling to diabetic patients not adhering to
      the optimal therapeutic pathway. The results suggest that the pharmacy might be
      able to implement an effective preventive action, particularly among socio
      economically disadvantaged people, thereby helping to reduce inequalities in
      care. The cost/effectiveness evaluation of long-term outcomes, based on the use
      of existing health information systems, will provide more accurate information on
      the value of the model.

PMID- 28492585
TI  - Biosimilars in oncology: everybody agrees but nobody uses?
AB  - Reducing the cost of biologics is an important avenue for addressing financial
      toxicity in oncology, one of the biggest challenges for health systems. The use
      of biosimilars, the cheaper alternatives to biologics, is an important strategy
      to that end. But the enthusiasm of developing biosimilars is meaningless if they
      get to the market, but they're not prescribed by the physicians, concerned by
      unexpected side effects or inferior efficacy. A recent study found no differences
      between biosimilars and erythropoietin stimulating agents originators in the
      composite outcome including all-cause mortality, blood transfusion and major
      cardiovascular events. Such studies are important to allay the concerns of
      physicians and patients regarding the use of biosimilars. Physician and patient
      education, backed by clinical guidelines and patient advocacy groups, are the
      keys to improving the uptake ofbiosimilars in clinical practice.

PMID- 28492586
TI  - [Risk of pneumonia during long term regular treatment of stable COPD with inhaled
      glucocorticoids: a systematic review.]
AB  - Inhaled glucocorticoids are anti-inflammatory drugs used in combination with long
      acting bronchodilators beta2-agonists for the treatment of stable chronic
      obstructive pulmonary disease (COPD), to improve lung function and symptoms and
      to reduce the future risk COPD exacerbations. However, has been also associated
      to an increased risk of pneumonia. The objective of this systematic review was
      therefore to analyze all randomized controlled trials to identify the risk of
      pneumonia during the regular treatment with long-term inhaled
      glucocorticosteroids compared to treatment with placebo in patients with stable
      COPD. From a literature search on PubMed, 19 randomized, placebo-controlled, long
      term (at least 52-week) studies have been identified. The inhaled glucocorticoids
      administered were: budesonide (6 studies), mometasone furoate (3 studies),
      beclomethasone dipropionate (1 study), triamcinolone acetonide (1 study),
      fluticasone propionate (7 studies) and fluticasone furoate (1 study). Only 7 of
      the 19 trials identified in our systematic review reported data on pneumonia and
      only one study required radiological evidence for diagnosis. The incidence of
      pneumonia was slightly increased in patients treated with glucocorticoid inhaled
      compared to placebo in most studies, regardless of the type of glucocorticoid
      inhalation used, suggesting a class effect. Older age, low body mass index, low
      FEV1, being a smoker are all factors variously associated with increased risk of
      pneumonia.

PMID- 28492587
TI  - [Intentional roundings in general medical practice: the experience of the Azienda
      Ospedali Riuniti Marche Nord (Italy).]
AB  - INTRODUCTION: The "intentional roundings" are planned rounds, conducted at
      regular intervals by nursing staff to anticipate care, comfort, hospitality and
      psychological needs of hospitalized users. These purposes are achieved with a
      structured way to make observations and carry out activities for well-being and
      patient safety, documenting what was done with a structured ad hoc form. In the
      United Kingdom, as well as in the USA, intentional rounding is an established
      model of care that improve the safety of provided care, to reduce the occurrence
      of preventable events, address proactively basic caring needs, and that increase
      users and staff satisfaction. OBJECTIVE: Implementing in a medical pilot unit the
      care model named "intentional rounding". METHODS: The care team carried
      intentional rounds every two hours, in a systematic and documented manner. All
      patients received admission informations about the organizational method and were
      invited to participate by completing a satisfaction questionnaire at discharge.
      At the end of the experimental period organizational impact have been
      investigated, specifically users and hospital staff satisfaction. RESULTS: About
      privacy, courtesy, nurse support and quality of care provided, level of
      satisfaction of patients and caregivers reached high percentage of approval (90
      99%). Nurses and other healthcare personnel have perceived they delivered either
      a safer and most satisfying healthcare (90-94%) as well as inter- and intra
      professional dynamics communications (95%). Value of roundings have been less
      appreciated concerning the optimization about the worktime management (79%).
      Calls to the bell have had a notable change of their reasons unlikely about the
      quantity. CONCLUSIONS: Intentional roundings affects very positively to users
      satisfaction level and to the perception of the quality of care provided; the
      care team, though express the need to make some changes for a real
      implementation, recognize the proactivity of intentional roundings as an added
      value.

PMID- 28492588
TI  - [A rare case of intussusception in a seventeen year old boy: diagnosis,
      management and review of the literature.]
AB  - Intussusception is the most common cause of intestinal obstruction and acute
      abdomen in the first year of life. Approximately in the 80% of cases
      intussusception occurs when the last ileal loop is pulled into the cecum, passing
      through the ileocecal valve, and finally resulting in the displacement of cecum
      in the upper abdominal. It could be related with mesenteric adenitis because
      enlarged lymph nodes, together with peristalsis, can serve as "lead point". Other
      forms of intussusception are ileo-ileal and colo-colic. The aetiology in infants
      and adults can be very variable and most often linked with secondary causes, such
      as benign or malignant lesions (polyps, tumors, lymphomas, intestinal duplication
      cyst, Meckel's diverticulum). In this paper we describe a rare case of idiopathic
      ileo-ileal intussusception in a 17 year old boy. We also discuss, with a careful
      analysis of the literature, the diagnostic and therapeutic protocol in case of
      intussusception ileo-colic approved at the Meyer Children's Hospital.

PMID- 28492590
TI  - ?

PMID- 28492589
TI  - [Marcato aumento delle concentrazioni di procalcitonina dopo idroclorotiazide
      edema polmonare indotta.]
AB  - INTRODUCTION: In the Medline database there are approximately 60 cases reporting
      toxic pulmonary edema, a life-threatening event, induced after consumption of
      hydrochlorothiazide, one of the most common antihypertensive drugs. Moreover,
      increased procalcitonin concentrations have been reported after cardiogenic
      pulmonary edema. We report the rare case of a hydrochlorothiazide-induced
      pulmonary edema, which was followed by a marked increase of the procalcitonin
      concentrations. CLINICAL CASE: A middle-aged woman was admitted to the Emergency
      Department for severe dyspnea and chills. Such symptoms began 30 minutes after
      consumption of hydrochlorothiazide. Her physical examination and chest-X-ray were
      compatible with pulmonary edema, however her brain natriuretic peptide levels and
      echocardiogram were almost normal. Interestingly she had extremely elevated
      procalcitonin concentrations with normal white blood cells count and C-reactive
      protein levels only mildly increased. We hypothesized toxic pulmonary edema and
      started treatment with non-invasive mechanical ventilation, with the patient
      presenting rapid clinical improvement. CONCLUSIONS: Even if extremely rare,
      hydrochlorothiazide may induce pulmonary edema; significant increase of
      procalcitonin concentrations may occur in this condition and perhaps in other
      cases of toxic pulmonary edema. Practitioners should be aware of this condition
      in order to spare expensive and useless, in this case, investigations such as
      blood cultures and treatments (antibiotics) if other signs of infection are
      absent.

PMID- 28492591
TI  - ?

PMID- 28492592
TI  - Electronic collaboration in dermatology resident training through social
      networking.
AB  - The use of online educational resources and professional social networking sites
      is increasing. The field of dermatology is currently under-utilizing online
      social networking as a means of professional collaboration and sharing of
      training materials. In this study, we sought to assess the current structure of
      and satisfaction with dermatology resident education and gauge interest for a
      professional social networking site for educational collaboration. Two surveys
      one for residents and one for faculty-were electronically distributed via the
      American Society for Dermatologic Surgery and Association of Professors of
      Dermatology (APD) listserves. The surveys confirmed that there is interest among
      dermatology residents and faculty in a dermatology professional networking site
      with the goal to enhance educational collaboration.

PMID- 28492593
TI  - Eruptive melanocytic nevi during azathioprine therapy for antisynthetase
      syndrome.
AB  - Eruptive melanocytic nevi (EMN) are rare multiple benign melanocytic nevi that
      develop within a few months. The phenomenon has been associated with a variety of
      dermatologic and systemic conditions, including Stevens-Johnson syndrome, toxic
      epidermal necrolysis, epidermolysis bullosa, Addison disease, human
      immunodeficiency virus infection, and internal malignancy, among others. It also
      is commonly attributed to medications, particularly immunosuppressive and
      chemotherapeutic agents. We report a case of EMN in a 50-year-old man undergoing
      azathioprine therapy for antisynthetase syndrome.

PMID- 28492594
TI  - Improving patient satisfaction in dermatology: a prospective study of an urban
      dermatology clinic.
AB  - Patient satisfaction has become an important measure of quality under the Patient
      Protection and Affordable Care Act. In this study, we assessed and analyzed
      patient satisfaction, nonattendance rates, and cycle times in an outpatient
      dermatology clinic. This study provides a snapshot of patient satisfaction in an
      urban dermatology clinic. Under the Patient Protection and Affordable Care Act,
      providers will be challenged to increase access to care and to validate quality
      of care through patient satisfaction.

PMID- 28492595
TI  - LGBT access to health care: a dermatologist's role in building a therapeutic
      relationship.

PMID- 28492596
TI  - Large hyperpigmented plaques on the trunk of a newborn.

PMID- 28492597
TI  - Pruritic rash on the buttock.

PMID- 28492598
TI  - Microneedling therapy with and without platelet-rich plasma.
AB  - Microneedling therapy is an increasingly popular treatment of several
      dermatologic conditions. Platelet-rich plasma (PRP) may serve as a valuable
      adjunct to improve the regenerative effects of treatment. We review the evidence
      comparing the results of microneedling therapy with and without PRP. Based on the
      current preliminary literature, PRP appears to augment the cosmetic outcomes of
      microneedling without increasing the risk for adverse events.

PMID- 28492599
TI  - Allergic reaction to vanadium causes a diffuse eczematous eruption and titanium
      alloy orthopedic implant failure.
AB  - Allergy as a cause of adverse outcomes in patients with implanted orthopedic
      hardware is controversial. Allergy to titanium-based implants has not been well
      researched, as titanium is traditionally thought to be inert. We highlight the
      case of a patient who developed systemic dermatitis and implant failure after
      surgical placement of a titanium alloy (Ti6Al4V) plate in the left foot. The
      hardware was removed and the eruption cleared in the following weeks. The plate
      and screws were submitted for metal analysis. The elemental composition of both
      the plate and screws included 3 major elements-titanium, aluminum, and vanadium
      as well as trace elements. Metal analysis revealed that the plate and screws had
      different microstructures, and electrochemical studies demonstrated that galvanic
      corrosion could have occurred between the plate and screws due to their different
      microstructures, contributing to the release of vanadium in vivo. The patient was
      patch tested with several metals including components of the implant and had a
      positive patch test reaction only to vanadium trichloride. These findings support
      a diagnosis of vanadium allergy and suggests that clinicians should consider
      including vanadium when patch testing patients with a suspected allergic reaction
      to vanadium-containing implants.

PMID- 28492600
TI  - Efinaconazole solution 10% for treatment of toenail onychomycosis in Latino
      patients.
AB  - Onychomycosis is a common progressive fungal infection of the nail bed, matrix,
      or plate leading to destruction and deformity of the toenails and fingernails.
      The prevalence of onychomycosis is increasing in the United States, particularly
      in the growing population of Latino patients. In this study, we evaluated the
      efficacy and safety of efinaconazole solution 10% in Latino patients with
      onychomycosis. Once-daily application of efinaconazole solution 10% may be an
      effective topical option for treatment of onychomycosis in this patient
      population.

PMID- 28492601
TI  - Flesh-colored nodule with underlying sclerotic plaque.

PMID- 28492602
TI  - Redness and painful ulcerations in the perineal area.

PMID- 28492603
TI  - Recovery of hair in the psoriatic plaques of a patient with coexistent alopecia
      universalis.

PMID- 28492604
TI  - Serpentine supravenous hyperpigmentation following cisplatin and pemetrexed
      chemotherapy.

PMID- 28492605
TI  - Severe refractory atopic dermatitis with elevated serum IgE treated with
      omalizumab.

PMID- 28492606
TI  - Expanding uses of propranolol in dermatology.
AB  - Propranolol as a dermatologic therapeutic tool was first described in 2008. Since
      then, propranolol has had a pivotal role in the dermatology arena for a myriad of
      cutaneous disorders. This article highlights the timeline of the incorporation of
      propranolol as a treatment option for a number of vascular lesions.

PMID- 28492607
TI  - Blepharoplasty markers: comparison of ink drying time and ink spread.
AB  - Marking of the eyelid is a crucial presurgical step in blepharoplasty. A number
      of markers are available for this purpose with variable ink characteristics. In
      this study, we measured the ink drying time and spread width of 13 markers used
      for preoperative marking for blepharoplasty. Based on the results, we propose
      markers that may be best suited for use in this procedure.

PMID- 28492608
TI  - Sinonasal symptom-related sleep disorders before and after surgery for nasal
      polyposis.
AB  - BACKGROUND: Patients with nasal polyposis (NP) complain of several sinonasal
      symptoms that impact their sleep and quality of life. However, data on sleep
      disorders related to NP symptoms, before and after surgery, is poor. The aim of
      the present study was to analyze sleep complaints related to each NP symptom,
      before and after surgery, using the Dynachron questionnaire. METHODOLOGY: 63
      patients operated for NP were included in this prospective study. They filled the
      DyNaChron questionnaire one day before surgery (V0), 6 weeks (V1) and 7 months
      (V2) after surgery. The self-ratings (0-10 point visual analog scale) of nasal
      obstruction, anterior rhinorrhea, postnasal discharge, cough and 5 items related
      to sleep disturbances, due to each symptom of chronic nasal dysfunction, were
      extracted from the questionnaire and analyzed. RESULTS: There was significant
      improvement of symptoms and symptom-related sleep disturbance scores at V1 and V2
      compared to baseline scores. Before surgery, moderate/severe sleep disorders that
      patients attributed to nasal obstruction (the patient thinks it is due to nasal
      obstruction rather than a clinical test to show nasal obstruction) or anterior
      rhinorrhea were reported in two thirds of patients, postnasal discharge in one
      half, and chronic cough in one third. After surgery, less than 10% of patients
      reported moderate/severe sleep disorders at V1. There was a mild increase of
      patients who rated moderate/severe sleep disorders at V2 in comparison to V1. The
      correlation between scores of nasal obstruction and its impacts on sleep quality
      was weak before surgery and strong afterwards. CONCLUSION: Nasalization improved
      sleep quality significantly at 6 weeks and at 7 months after surgery. However,
      there was a mild increase of complaints related to postnasal discharge and cough
      at 7 months after surgery.

PMID- 28492609
TI  - The risk of osteoporosis in oral steroid treatment for nasal polyposis: a
      systematic review.
AB  - BACKGROUND: Systemic glucocorticoids are often used in the treatment of chronic
      rhinosinusitis with nasal polyps (CRSwNP), and osteoporosis is a well-known
      complication to steroid treatment, associated with significant morbidity.
      Nevertheless, the burden of steroid induced osteoporosis is unknown in patients
      with CRSwNP. We aimed to assess the risk of acquiring osteoporosis caused by oral
      steroids in patients with CRSwNP, and provide recommendations on future research
      and guidelines. METHODOLOGY: Cochrane Review Database, EMBASE, Ovid Medline, and
      PubMed were searched for studies including adult patients with CRSwNP treated
      with oral steroids. Outcomes were Bone Mineral Density (BMD) and prevalence of
      fractures in relation to dose and duration of oral steroids. In addition, we
      reviewed general guidelines for treatment with oral steroids. RESULTS: We
      identified two studies (n=243) that met the inclusion criteria. Doses and
      durations of oral steroids were over 5 mg/day for more than 3 months and 1 mg/kg
      body weight/day for 6 to 10 days for 4 or more courses/year. The prevalence of
      low bone mass was 39% and 61%, respectively. It was not possible to quantify the
      overall risk of osteoporosis induced by oral steroids from the studies. No
      studies evaluated prevalence of fracture. CONCLUSIONS: Registry studies and
      randomized controlled trials would be needed to assess the risk of osteoporosis
      in CRSwNP patients and future guidelines should include recommendations regarding
      preventive treatment and recommendations on doses and durations of oral steroids.

PMID- 28492610
TI  - Nasal cytology in children: scraping or swabbing?
AB  - Nasal cytology has become a valuable tool in the assessment of a multitude of
      nasal pathologies in children. Collection methods differ significantly and even
      though the use of the nasal curette is regarded as the most reliable in adults,
      most practitioners use the nasal swab in children. However, no studies have
      validated the reliability and supposed better tolerability of the latter. We have
      compared these two sampling methods regarding their tolerability and analysed the
      diagnostic accuracy of the cotton nasal swab (NSW) to identify nasal cytotypes
      and rhinitis phenotypes, using nasal scraping (NSC) for comparison. In a
      multicentric prospective study we recruited 208 children and performed nasal
      cytology by means of NSW and NSC. Microscopic evaluating of the nasal cytotypes
      was performed and tolerability of NSW and NSC was tested. Our data revealed a
      significantly inferior diagnostic accuracy of NSW compared to NSC regarding
      reliability and cell counts. Our study is the first to shed light on the role of
      the sampling tools for pediatric nasal cytology. We documented a poor diagnostic
      accuracy of NSW, thus suggesting using only the nasal curette in clinical
      practice. Furthermore, tolerability did not differ between the two, refuting the
      common thesis that swabs are to be preferred when doing nasal cytology in
      children.

PMID- 28492611
TI  - The effect of topical treatments for CRS on the sinonasal epithelial barrier.
AB  - BACKGROUND: Several topical treatments are used in the management of Chronic
      Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be
      determined. The purpose of this study was to investigate the effect of commonly
      used topical treatments on the sinonasal epithelial barrier. METHODS: Normal
      saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu
      Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the
      apical side of air-liquid interface (ALI) cultures of primary human nasal
      epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for
      24 hours. Epithelial barrier structure and function was assessed using trans
      epithelial electrical resistance (TEER), measuring the passage of Fluorescein
      Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of
      the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence.
      Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was
      analysed using ANOVA, followed by Tukey HSD post hoc test. RESULTS: Hypertonic
      solution and budesonide significantly increased TEER values in CRS derived HNECs.
      In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes
      after application of the solution followed by an increase in paracellular
      permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after
      application of the solution. CONCLUSIONS: Our findings confirm that isotonic and
      hypertonic saline solutions do not compromise epithelial barrier function in
      vitro but underscore the importance of examining safety and efficacy of over-the
      counter wash solutions.

PMID- 28492612
TI  - A prospective, randomized clinical study comparing drug eluting stent therapy and
      intranasal corticoid steroid therapy in the treatment of patients with chronic
      rhinosinusitis.
AB  - OBJECTIVES: To conduct the first prospective, randomized controlled clinical
      trial comparing the efficacy of a drug-eluting stent (DES) (the Relieva StratusTM
      MicroFlow Spacer) and topical intranasal corticosteroid therapy in patients with
      chronic rhinosinusitis (CRS). METHODS: Sixty-three adult patients with
      ethmoiditis were randomized into either the DES group (n=34) or nasal spray group
      (n=29). The main outcome variable was the Sinonasal Outcome Test 22, Visual
      Analogue Scale, nasal endoscopy, rhinometric measurements were performed at the
      beginning of the study, after three months and six months of follow-up. RESULTS:
      Both treatments significantly improved quality of the life with no significant
      difference being found between the two groups. The VAS score decreased in both
      groups: improvements were significant at three and six months in the nasal spray
      group, but in the DES group a significant difference was noted only at three
      months. There was a statistically significant increase in total nasal cavity
      volumes in the corticosteroid spray group, but not in the DES group. CONCLUSION:
      We found that patients benefitted from DES and the corticosteroid nasal spray. We
      could not find any significant difference between the treatments, except the
      greater increase in the total nasal cavity volumes favouring the nasal spray
      group. Because of the very good results for the nasal spray and the much higher
      material and operating room costs associated with DES, we cannot recommend the
      use of DES over nasal spray as a monotherapeutic treatment for CRS.

PMID- 28492613
TI  - Erratum. Correction to: Hu X, et al. Acoustic Radiation Force Impulse (ARFI)
      Elastography for non-invasive evaluation of hepatic fibrosis in chronic hepatitis
      B and C patients: a systematic review and meta-analysis. Med Ultrason 2017;
      19(1):23-3.
AB  - The authors have been made aware of the errors that appeared at Corresponding
      author: correct phone number 86-10-63138297 and correct email
      qianlinxue2002@163.com, and also at acknowledgements: correct grant no. 2014-3
      009.

PMID- 28492618
TI  - Unexpected coordination number and phase diagram of niobium diselenide under
      compression.
AB  - We discovered several new energetically competitive structures of NbSe2 using the
      multi-algorithm collaborative (MAC) crystal structure prediction algorithm
      combined with the density functional theory. It was found that the coordination
      number of Nb in NbSe2 is increased from 6 to 7, and then to 8 with increasing
      pressure. Furthermore, it was unexpected that an Se atom would be squeezed to the
      center of a cage formed by 12 other Se atoms and then have 12-fold coordination
      when the pressure was increased to 130.4 GPa. The 12-coordination metalloid atom
      has never been discovered in other transition metal dichalcogenides. The new
      C2/m, I4/mmm, and P4/mmm NbSe2 were verified to be stable under both dynamically
      and mechanically stabile conditions. It is especially noteworthy that the new
      C2/m-NbSe2 was predicted to be potentially synthesized at high pressure and
      recovered under ambient conditions. A detailed high-pressure and high-temperature
      phase diagram was constructed based on the quasi-harmonic approximation up to 200
      GPa, and the synthesis conditions of different new NbSe2 materials were also
      analyzed. All the discoveries in this study will guide the future synthesis of
      new NbSe2 materials at specific pressure and under temperature conditions and
      also help to further understand other transition metal dichalcogenides.

PMID- 28492619
TI  - The hot carrier diffusion coefficient of sub-10 nm virgin MoS2: uncovered by non
      contact optical probing.
AB  - We report a novel approach for non-contact simultaneous determination of the hot
      carrier diffusion coefficient (D) and interface thermal resistance (R) of sub-10
      nm virgin mechanically exfoliated MoS2 nanosheets on c-Si. The effect of hot
      carrier diffusion in heat conduction by photon excitation, diffusion, and
      recombination is identified by varying the heating spot size from 0.294 MUm to
      1.14 MUm (radius) and probing the local temperature rise using Raman
      spectroscopy. R is determined as 4.46-7.66 * 10-8 K m2 W-1, indicating excellent
      contact between MoS2 and c-Si. D is determined to be 1.18, 1.07, 1.20 and 1.62
      cm2 s-1 for 3.6 nm, 5.4 nm, 8.4 nm, and 9.0 nm thick MoS2 samples, showing little
      dependence on the thickness. The hot carrier diffusion length (LD) can be
      determined without knowledge of the hot carrier's life-time. The four samples LD
      is determined as 0.344 (3.6 nm), 0.327 (5.4 nm), 0.346 (8.4 nm), and 0.402 MUm
      (9.0 nm). Unlike previous methods that are implemented by making electrical
      contact and applying an electric field for D measurement, our technique has the
      advantage of being truly non-contact and non-invasive, and is able to
      characterize the electron diffusion behavior of virgin 2D materials. Also it
      points out that hot carrier diffusion needs to be taken into serious
      consideration in Raman-based thermal property characterization of 2D materials,
      especially under very tightly focused laser heating whose spot size is comparable
      to the hot carrier diffusion length.

PMID- 28492620
TI  - Novel red phosphors KBaEu(XO4)3 (X = Mo, W) show high color purity and high
      thermostability from a disordered chained structure.
AB  - Two novel red phosphors KBaEu(XO4)3 (X = Mo, W) have been synthesized by high
      temperature solid-state reactions and the crystal structures were determined for
      the first time. Single-crystal X-ray diffraction data reveal that their space
      groups are C2/c. The crystalline structure is constituted of K/BaO8 distorted
      square antiprisms and distorted EuO8 polyhedra which form chains lying along the
      c-axis and two kinds of distorted XO4 tetrahedra. This high disorder of K/Ba
      which might lower the crystal field symmetry around Eu3+ results in the high
      purity of red emission around 615 nm originating from 5D0 -> 7F2 transition under
      near-ultraviolet (NUV) excitation. With increasing temperature, the luminescence
      of KBaEu(XO4)3 (X = Mo, W) phosphors decreases almost linearly with subtle
      alteration for the CIE coordinate. As the temperature reaches 550 K, the red
      emission intensity decreases to 37.3% and 50.7% of that at 300 K for KBaEu(MoO4)3
      and KBaEu(WO4)3, respectively. The analysis of the decay curves of the 5D0 -> 7F2
      emission at variable temperatures indicates the weak cross relaxation and non
      radiative energy transfer between Eu3+ ions. These results demonstrate that the
      investigated phosphors are attractive for application in high power NUV excited
      white LEDs.

PMID- 28492621
TI  - Leaf parts from Greek artichoke genotypes as a good source of bioactive compounds
      and antioxidants.
AB  - Globe artichoke is an important vegetable in the Mediterranean diet. However, the
      marketable part of the plant constitutes a small portion of its total crop
      biomass and large amounts of waste are produced during its cultivation. In this
      study, the phenolic compound content and composition and the antioxidant activity
      of leaf parts [blades (SLB), petioles and midribs (SPM)] from various Greek
      artichoke genotypes were evaluated. The results showed significant variation in
      antioxidant activities and bioactive compound contents between the studied
      genotypes, with the leaf blades of most of the genotypes having a high content of
      flavonoids (mainly luteolin glycoside derivatives), which ranged between 49 and
      78% of total phenolic compounds (TPC). In contrast, in petioles and midribs
      phenolic acids (mainly hydroxycinnamic acid derivatives) were the main phenolic
      compounds, ranging between 64 and 76% of TPC. The antioxidant activity of blades
      was significantly higher than that of petiole and midribs for all the genotypes
      and the tested assays. In conclusion, artichoke leaves (blades, petioles and
      midribs) of the studied genotypes showed different bioactive compound profiles
      and significant antioxidant properties, and could be further used in the food and
      nutraceuticals industries as a cheap source of phenolic compounds and
      antioxidants.

PMID- 28492622
TI  - Isolated, well-defined organovanadium(iii) on silica: single-site catalyst for
      hydrogenation of alkenes and alkynes.
AB  - A well-defined, isolated, single-site organovanadium(iii) catalyst on SiO2
      [(SiO2)V(Mes)(THF)] was synthesized via surface organometallic chemistry, and
      fully characterized using a combination of analytical and spectroscopic
      techniques (EA, ICP, 1H NMR, TGA-MS, EPR, XPS, DR-UV/Vis, UV-Raman, DRIFTS, XAS).
      The catalyst exhibits unprecedented reactivity in liquid- and gas-phase
      alkene/alkyne hydrogenation. Kinetic poisoning experiments revealed that 100% of
      the V sites are active for hydrogenation.

PMID- 28492623
TI  - The use of carboxylic acids as traceless directing groups for regioselective C-H
      bond functionalisation.
AB  - The ability to selectively functionalise a specific C-H bond is a long-standing
      challenge due to the ubiquity of such bonds in organic molecules. One of the most
      common approaches to overcome this obstacle consists of installing directing
      groups into substrates to direct the functionalisation towards the desired C-H
      bond, leaving behind the directing group in the molecule. Alternatively,
      carboxylic acids have been employed as traceless directing groups that are easily
      removed after carboxylic acid-directed installation of the desired functionality.
      This review focuses on the development of this concept and its application to
      organic synthesis during the last decade.

PMID- 28492624
TI  - A simple quinolone Schiff-base containing CHEF based fluorescence 'turn-on'
      chemosensor for distinguishing Zn2+ and Hg2+ with high sensitivity, selectivity
      and reversibility.
AB  - A new simple 'dual' chemosensor MQA ((E)-2-methoxy-N-((quinolin-2
      yl)methylene)aniline) for distinguishing Zn2+ and Hg2+ has been designed,
      synthesized and characterized. The sensor showed excellent selectivity and
      sensitivity with a fluorescence enhancement to Zn2+/Hg2+ over other commonly
      coexisting cations (such as Na+, Mg2+, Al3+, K+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+,
      Cu2+, Ga3+, Cd2+, In3+ and Pb2+) in DMSO-H2O solution (1/99 v/v), which was
      reversible with the addition of ethylenediaminetetraacetic acid (EDTA). The
      detection limit for Zn2+/Hg2+ by MQA both reached the 10-8 M level. The 1 : 1
      ligand-to-metal coordination patterns of the MQA-Zn2+ and MQA-Hg2+ were
      calculated through a Job's plot and ESI-MS spectra, and were further confirmed by
      X-ray crystal structures of complexes MQA-Zn2+ and MQA-Hg2+. This chemosensor can
      recognize similar metal ions by coherently utilizing intramolecular charge
      transfer (ICT) and different electronic affinities of various metal ions. DFT
      calculations have revealed that the energy gap between the HOMO and LUMO of MQA
      has decreased upon coordination with Zn(ii)/Hg(ii).

PMID- 28492625
TI  - Thermal convection in electrochemical cells. Boundaries with heterogeneous
      thermal conductivity and implications for scanning electrochemical microscopy.
AB  - We investigate the heat transfer in a cylinder-shaped electrochemical cell with
      solid, thermally insulating walls. The cell is filled with a liquid and a solid
      substrate that is thermostated from below is situated at its base. The initial
      temperature of the liquid is different from that of the substrate so as to mimic
      imperfect thermostating in an electrochemical experiment; as heat transfer acts
      to diminish the temperature difference between the two, natural convection
      ensues. The influence of inhomogeneities in the thermal conductivity of the solid
      is studied - numerical simulations of the heat transfer in the system are
      conducted for substrates that are comprised of a thermally conductive material,
      an insulating one or a combination thereof. It is shown that the substrate
      structure strongly influences the structure and intensity of the natural
      convective flows emerging in the system. The present work demonstrates that under
      the idealized conditions under consideration, depending on the substrate
      structure, natural convection due to imperfect solution thermostating may give
      rise to flows whose local velocity can reach values as high as 10-3 m s-1.
      Moreover, as comparison between cells of two different radii shows, both the
      intensity and the temporal evolution of the flows arising in this system are
      highly sensitive to the precise geometry of the experimental cell. These results
      can have far-reaching consequences for the interpretation of results from
      experimental techniques such as scanning electrochemical microscopy.

PMID- 28492626
TI  - Alkynyl sulfoxides as alpha-sulfinyl carbene equivalents: gold-catalysed
      oxidative cyclopropanation.
AB  - Alkynyl sulfoxides are shown to act as alpha-sulfinyl metallocarbene synthons
      under oxidative gold catalysis, enabling reactions that are not available from
      diazo-precursors. This strategy is exemplified in the synthesis of fused alpha
      sulfinyl cyclopropanes.

PMID- 28492627
TI  - Analysis of the electron transfer properties of carbon quantum dots on gold
      nanorod surfaces via plasmonic resonance scattering spectroscopy.
AB  - Carbon quantum dot wrapped gold nanorods were fabricated on an ITO electrode
      surface via electrostatic interactions. The electron transfer properties of
      carbon quantum dots on gold nanorod surfaces were systematically investigated by
      plasmonic resonance scattering spectroscopy.

PMID- 28492628
TI  - Lanthanide separation using size-selective crystallization of Ln-MOFs.
AB  - Herein, we report an elaborate method, size-selective crystallization of Ln-MOFs,
      to isolate lanthanide (Ln) ions. Herein, 13 lanthanide ions, except for the
      radioactive Pm(iii) ion, were separated by four types of Ln-MOFs: type I (La-Pr),
      type II (Nd-Eu), type III (Gd-Ho), and type IV (Er-Lu). Further systemic
      investigation also suggested the highly selective separation of lanthanide ions
      by this method.

PMID- 28492629
TI  - Liquid/vapor-induced reversible dynamic structural transformation of a three
      dimensional Cu-based MOF to a one-dimensional MOF showing gate adsorption.
AB  - A new 3D metal-organic framework (MOF), in which 2D layers are interlaced to form
      a 3D architecture, was synthesized by a reaction of Cu(BF4)2 and 1,3-bis(4
      pyridyl)propane (bpp) in a water/1-hexanol solvent system, and the crystal
      structure of the MOF was successfully solved. The MOF is reversibly transformed
      to a 1D chain MOF, which shows gate adsorption properties. The dynamic
      transformation gives crystal size reduction resulting in a slight change in CO2
      adsorption isotherms. The 1D MOF shows selective adsorption/separation properties
      on benzene and its analogues with similar sizes and shapes (benzene, toluene, and
      cyclohexane).

PMID- 28492630
TI  - One-step large-scale highly active g-C3N4 nanosheets for efficient sunlight
      driven photocatalytic hydrogen production.
AB  - The development of highly active, cost-effective, environmentally friendly and
      stable g-C3N4 based photocatalysts for H2 evolution is one of the most
      anticipated potential pathways for future hydrogen utilization. Herein, a facile
      gaseous bubble template approach was designed to prepare large-scale thin g-C3N4
      nanosheets (g-C3N4 NSs) using melamine and ammonium sulphate as the bubble
      template. Through distinctive structural improvements for a large bandgap,
      excellent electron mobility, prolonged lifetime of the photogenerated charge
      carriers and a high specific surface area with highly accessible potential
      reaction sites, the as-synthesized g-C3N4 NSs demonstrated a high photocatalytic
      hydrogen evolution rate of 9871 MUmol h-1 g-1 and efficient photocatalytic
      degradation of Rhodamine B (RhB) and phenol under simulated solar light
      irradiation.

PMID- 28492631
TI  - Molecular tectonics: gas adsorption and chiral uptake of (l)- and (d)-tryptophan
      by homochiral porous coordination polymers.
AB  - Combinations of two enantiomerically pure organic tectons 1 and 3 with either
      Zn(ii) or Cu(ii) cations lead to the formation of four homochiral 3D networks
      among which two, 1-Cu and 3-Cu, are robust porous crystals displaying homochiral
      cavities and permanent microporosity. 3-Cu porous crystals capture 66% and 20% of
      l- and d-tryptophan, respectively, after 30 min of adsorption.

PMID- 28492632
TI  - Photo-assisted inactivation of Escherichia coli bacteria by silver functionalized
      titanate nanotubes, Ag/H2Ti2O5.H2O.
AB  - One-dimensional titanate nanotubes (H2Ti2O5.H2O) functionalized with silver
      nanoparticles (AgNPs) exhibited unique properties for the effective inactivation
      of the Gram-negative Escherichia coli within 45 minutes under irradiation using a
      65 W halogen lamp. The pathway of the photo-assisted catalytic inactivation was
      examined by SEM and TEM using a reproducible biological protocol for sample
      preparations. The membrane integrity of the bacteria was damaged due to the
      oxidative stress caused by the reactive oxygen species, the bacteriostatic effect
      of the highly-dispersed-surface AgNPs (~5 nm) and the sharp nanotube penetration
      that induced the cell death.

PMID- 28492633
TI  - Rational molecular design enhancing the photonic performance of red-emitting
      perylene bisimide dyes.
AB  - We report the synthesis of novel multichromophoric organic architectures, where
      perylene red is decorated with BODIPY and/or hydroxycoumarin dyes acting as light
      harvesters and energy donors. The computationally-aided photophysical study of
      these molecular assemblies reveals a broadband absorption which, regardless of
      the excitation wavelength, leads solely to a bright red-edge emission from
      perylene bisimide after efficient intramolecular energy transfer hops. The
      increase of the absorbance of these molecular antennas at key pumping wavelengths
      enhances the laser action of the commercial perylene red. The herein applied
      strategy based on energy transfer dye lasers should boost the use of perylene
      based dyes as active media for red-emitting lasers.

PMID- 28492634
TI  - Transcriptional regulatory proteins as biosensing tools.
AB  - We have developed sensing systems employing different classes of transcriptional
      regulatory proteins genetically and chemically modified to incorporate a
      fluorescent reporter molecule for detection of arsenic, hydroxylated
      polychlorinated biphenyls (OH-PCBs), and cyclic AMP (cAMP). These are the first
      examples of optical sensing systems based on transcriptional regulatory proteins.

PMID- 28492640
TI  - Impedimetric measurement of DNA-DNA hybridisation using microelectrodes with
      different radii for detection of methicillin resistant Staphylococcus aureus
      (MRSA).
AB  - Due to their electroanalytical advantages, microelectrodes are a very attractive
      technology for sensing and monitoring applications. One highly important
      application is measurement of DNA hybridisation to detect a wide range of
      clinically important phenomena, including single nucleotide polymorphisms (SNPs),
      mutations and drug resistance genes. The use of electrochemical impedance
      spectroscopy (EIS) for measurement of DNA hybridisation is well established for
      large electrodes but as yet remains relatively unexplored for microelectrodes due
      to difficulties associated with electrode functionalisation and impedimetric
      response interpretation. To shed light on this, microelectrodes were initially
      fabricated using photolithography and characterised electrochemically to ensure
      their responses matched established theory. Electrodes with different radii (50,
      25, 15 and 5 MUm) were then functionalised with a mixed film of 6-mercapto-1
      hexanol and a thiolated single stranded DNA capture probe for a specific gene
      from the antibiotic resistant bacterium MRSA. The complementary oligonucleotide
      target from the mecA MRSA gene was hybridised with the surface tethered ssDNA
      probe. The EIS response was evaluated as a function of electrode radius and it
      was found that charge-transfer (RCT) was more significantly affected by
      hybridisation of the mecA gene than the non-linear resistance (RNL) which is
      associated with the steady state current. The discrimination of mecA
      hybridisation improved as electrode radius reduced with the RCT component of the
      response becoming increasingly dominant for smaller radii. It was possible to
      utilise these findings to produce a real time measurement of oligonucleotide
      binding where changes in RCT were evident one minute after nanomolar target
      addition. These data provide a systematic account of the effect of microelectrode
      radius on the measurement of hybridisation, providing insight into critical
      aspects of sensor design and implementation for the measurement of clinically
      important DNA sequences. The findings open up the possibility of developing
      rapid, sensitive DNA based measurements using microelectrodes.

PMID- 28492641
TI  - Rapid synthesis of bicyclic lactones via palladium-catalyzed aminocarbonylative
      lactonizations.
AB  - A novel and efficient palladium-catalyzed aminocarbonylative lactonization of
      amino propargylic alcohols has been developed to provide rapid access to various
      bicyclic lactones especially dihydropyrrole-fused furanones, which are novel
      structures and have not been explored in biological and medicinal settings. This
      method can also be used to access beta-lactone products such as 16. Preliminary
      biological evaluations revealed that compounds 13h and 13s demonstrated promising
      activity against Clostridium difficile and compounds 13h, 13k, 13s, and 16b
      showed activity against several important fungal pathogens.

PMID- 28492642
TI  - Copper-catalyzed remote (delta) C(sp3)-H bond amination: a practical strategy to
      construct pyrrolidine derivatives.
AB  - We report a copper-catalyzed remote C(sp3)-H bond amination reaction that
      converts acyclic amines to pyrrolidines. This reaction occurs selectively at the
      carbon delta to the amine functionality. Primary, secondary and tertiary C-H
      bonds are all suitable for the amination reactions in the presence of an
      inexpensive and commercially available copper catalyst.

PMID- 28492643
TI  - The influence of substituents and the environment on the NMR shielding constants
      of supramolecular complexes based on A-T and A-U base pairs.
AB  - In the present study, we have theoretically analyzed supramolecular complexes
      based on the Watson-Crick A-T and A-U base pairs using dispersion-corrected
      density functional theory (DFT). Hydrogen atoms H8 and/or H6 in the natural
      adenine and thymine/uracil bases were replaced, respectively, by substituents X8,
      Y6 = NH-, NH2, NH3+ (N series), O-, OH, OH2+ (O series), F, Cl or Br (halogen
      series). We examined the effect of the substituents on the hydrogen-bond lengths,
      strength and bonding mechanism, and the NMR shielding constants of the C2-adenine
      and C2-thymine/uracil atoms in the base pairs. The general belief in the
      literature that there is a direct connection between changes in the hydrogen-bond
      strength and the C2-adenine shielding constant is conclusively rejected by our
      computations.

PMID- 28492644
TI  - Temperature switchable Bronsted acid-promoted selective syntheses of spiro
      indolenines and quinolines.
AB  - A high-yielding, temperature switchable divergent approach towards the synthesis
      of either spiro-indolenines or quinolines is described, starting from easily
      available indolyl ynones. The application of TFA at rt promotes the
      dearomatization of the indole, resulting in the formation of the spiro
      indolenine, while at higher temperature, rearrangement results in the formation
      of the quinoline.

PMID- 28492645
TI  - A coordination strategy to realize a sextuply-bonded complex.
AB  - The synthesis of higher-order multiple bonds is a great challenge in chemistry.
      However, no stable compound with a sextuple bond has been reported, except for
      Mo2 in an inert matrix at low temperatures. Herein, we propose a strategy to
      construct a sextuple bond in a dinuclear transition metal complex based on
      complete active space second-order perturbation theory (CASPT2) and density
      functional theory calculations. When the dinuclear core M2 (M = W, Mo, and Re+)
      is capped by two neutral electron-donating ligands at both M-M ends, a sextuple
      bond can be realized. The proposed ligands stabilize the M2 core by the
      coordination, conserve the six bonding orbitals in the occupied space, and
      suppress the weight of the delta-delta* excited electronic configuration.
      Calculated large formation energies of these complexes indicate the large
      possibility of the synthesis. Electronic structures and sextuply bonding
      interactions were analyzed in detail.

PMID- 28492646
TI  - High pressure micromechanical force measurements of the effects of surface
      corrosion and salinity on CH4/C2H6 hydrate particle-surface interactions.
AB  - In order to investigate the mechanism of gas hydrate deposition and agglomeration
      in gas dominated flowlines, a high-pressure micromechanical force (MMF) apparatus
      was applied to directly measure CH4/C2H6 hydrate adhesion/cohesion forces under
      low temperature and high pressure conditions. A CH4/C2H6 gas mixture was used as
      the hydrate former. Adhesion forces between hydrate particles and carbon steel
      (CS) surfaces were measured, and the effects of corrosion on adhesion forces were
      analyzed. The influences of NaCl concentration on the cohesion force between
      CH4/C2H6 hydrate particles were also studied for gas-dominated systems. It was
      observed that there was no measurable adhesion force for pristine (no corrosion)
      and corroded surfaces, when there was no condensed water or water droplet on
      these surfaces. With water on the surface (the estimated water amount was around
      1.7 MUg mm-2), a hydrate film growth process was observed during the measurement.
      CS samples were soaked in NaCl solution to obtain different extents of corrosion
      on surfaces, and adhesion measurements were performed on both pristine and
      corroded samples. The adhesion force was found to increase with increasing soak
      times in 5 wt% NaCl (resulting in more visual corrosion) by up to 500%. For the
      effect of salinity on cohesion forces, it was found that the presence of NaCl
      decreased the cohesion force between hydrate particles, and a possible
      explanation of this phenomenon was given based on the capillary liquid bridge
      model.

PMID- 28492647
TI  - Synthesis of water-soluble palladium(ii) complexes with N-heterocyclic carbene
      chelate ligands and their use in the aerobic oxidation of 1-phenylethanol.
AB  - The synthesis of palladium(ii) complexes containing N-heterocyclic carbene
      chelate ligands is reported. These chelate ligands have methylene or ethylene
      ring bridges and sulfonate, carbonate or ammonium functionalities to render the
      complexes soluble in water. Bis- [(bis-NHC)PdX2] (X = Cl, Br or I) and tetra
      carbene [(bis-NHC)2Pd] complexes have been prepared and the crystal structures of
      two of them have been determined. The NHC ligand is coordinated to the metal
      center in normal (C2-bound) or abnormal (C4-bound) mode. Processes involving the
      formation of NHC-Pd bonds or the transfer of NHC ligands have been explored in
      water. The behavior of the bis-carbene complexes as catalysts for the aerobic
      oxidation of 1-phenylethanol is also discussed.

PMID- 28492648
TI  - Unifying hydrotropy under Gibbs phase rule.
AB  - The task of elucidating the mechanism of solubility enhancement using hydrotropes
      has been hampered by the wide variety of phase behaviour that hydrotropes can
      exhibit, encompassing near-ideal aqueous solution, self-association, micelle
      formation, and micro-emulsions. Instead of taking a field guide or encyclopedic
      approach to classify hydrotropes into different molecular classes, we take a
      rational approach aiming at constructing a unified theory of hydrotropy based
      upon the first principles of statistical thermodynamics. Achieving this aim can
      be facilitated by the two key concepts: (1) the Gibbs phase rule as the basis of
      classifying the hydrotropes in terms of the degrees of freedom and the number of
      variables to modulate the solvation free energy; (2) the Kirkwood-Buff integrals
      to quantify the interactions between the species and their relative contributions
      to the process of solubilization. We demonstrate that the application of the two
      key concepts can in principle be used to distinguish the different molecular
      scenarios at work under apparently similar solubility curves observed from
      experiments. In addition, a generalization of our previous approach to solutes
      beyond dilution reveals the unified mechanism of hydrotropy, driven by a strong
      solute-hydrotrope interaction which overcomes the apparent per-hydrotrope
      inefficiency due to hydrotrope self-clustering.

PMID- 28492649
TI  - Identifying electrochemical effects in a thermal-electrochemical co-driven system
      for CO2 capture.
AB  - Currently, the most promising amine absorption system for CO2 capture still faces
      the challenges of heavy steam consumption and a high energy penalty. Thus, a new
      thermal-electrochemical co-driven system (TECS) for CO2 capture was developed to
      resolve these problems. In the TECS, unknown electrochemical behaviors are quite
      essential to assess the CO2 capture performance. Electrochemical experiments were
      designed using response surface methodology (RSM) to identify electrochemical
      effects. The results show that the cathode process is slow and difficult, which
      is the main limitation in improving the performance of the TECS. Forced
      convection is necessary to improve the diffusion-controlled process and
      accelerate desorption. Four factors (Cu(ii) molality, CO2 loading, temperature,
      KNO3 molality) play an auxo-action role in determining anode and cathode reaction
      rates. A regression model is developed based on the experimental data, and
      optimum operating conditions are obtained. Regeneration energy consumption
      reaches about 1.3 GJ per t CO2, a decline of up to 70% compared with the
      traditional process. In addition, preliminary CO2 desorption experiments suggest
      that the mass transfer ascribed to the electrochemical process accounts for over
      50% of the overall mass transfer coefficient in the CO2 desorption process.

PMID- 28492650
TI  - Stabilization of a t-ZrO2 polymorph in a glassy SiO2 matrix at elevated
      temperatures accomplished by ceria additions.
AB  - Glass-ceramic composites are considered important candidates for load bearing
      orthopaedic applications owing to their combined salient features of bioactivity
      and mechanical strength. Herein, we report the impact of ceria (CeO2) additions
      on the structural and mechanical behaviour of ZrO2-SiO2 binary oxides as a glass
      ceramic composite for hard tissue replacements. A wide range of ceria additions
      to the ZrO2-SiO2 system have been performed via sol-gel synthesis. The structural
      behaviour of the synthesized compositions is investigated at elevated
      temperatures using a combination of XRD, Raman spectroscopy, TEM and SEM. The
      stabilization of tetragonal zirconia (t-ZrO2) and CeO2 in the presence of an
      amorphous SiO2 matrix under heat treatment up to 1300  degrees C was confirmed.
      The t-ZrO2 phase is stabilised through Ce4+ substitution up to 20 wt% CeO2
      additions, and above this CeO2 crystallization occurs in the amorphous matrix.
      The morphological and mechanical behaviour of the ceramic reinforced glass matrix
      is presented with the CeO2 stabilised system showing mechanical properties
      comparable with commercial biomaterial systems.

PMID- 28492651
TI  - The influence of carbon concentration on the electronic structure and magnetic
      properties of carbon implanted ZnO thin films.
AB  - The influence of carbon concentration on the electronic and magnetic properties
      of C-implanted ZnO thin films has been studied using synchrotron radiation based
      X-ray absorption spectroscopic techniques and vibrating sample magnetometer
      measurements. 20 keV carbon ions were implanted in ZnO films with different
      fluences (2 * 1016, 4 * 1016 and 6 * 1016 ions per cm2). The pristine ZnO film
      shows diamagnetic behaviour while the C-implanted films exhibit room temperature
      ferromagnetism. Our first-principles calculations based on density functional
      theory show an appreciable magnetic moment only when the implanted C atom sits
      either in the O-site (2 MUB) or in the interstitial position (1.88 MUB), whereas
      the C atom in the Zn substitutional position does not possess any magnetic
      moment. X-ray absorption near edge structure analysis at the O K-edge reveals
      that the charge transfer from O-2p to the C-defect site causes the ferromagnetism
      in the C-implanted ZnO film at low fluence. However at high fluence, the
      implanted C replaces the lattice and produces more Zn vacancies, as evidenced by
      extended X-ray absorption fine structure studies at the Zn K-edge, which favors
      the ferromagnetism. The persistence of the implanted carbon and ferromagnetism of
      the C-implanted ZnO film has also been studied by isothermal annealing at 500 
      degrees C and discussed in detail.

PMID- 28492652
TI  - Low energy electron-induced decomposition of (eta3-C3H5)Ru(CO)3Br, a potential
      focused electron beam induced deposition precursor with a heteroleptic ligand
      set.
AB  - Here we describe in detail low energy electron induced fragmentation of a
      potential focused electron beam induced deposition (FEBID) precursor, pi-allyl
      ruthenium tricarbonyl bromide, i.e. (eta3-C3H5)Ru(CO)3Br, specially designed to
      allow comparison of the effect of different ligands on the efficiency of low
      energy electron induced fragmentation of FEBID precursors. Specifically, we
      discuss the efficiency of dissociative electron attachment (DEA) and dissociative
      ionization (DI) with respect to electron-induced removal of the allyl, bromide
      and carbonyl ligands. We place this in perspective with a previous surface study
      on the same precursor and we propose a design strategy for FEBID precursor
      molecules to increase their susceptibility towards DEA.

PMID- 28492654
TI  - Microstructure based prediction of the deformation behavior of soft collagenous
      membranes.
AB  - The response of human amnion (HA) and bovine Glisson's capsule (GC) to uniaxial
      and biaxial tensile loading is analyzed on tissue (~mm) and collagen fiber (~MUm)
      length scales. The mechanical behavior of the membranes is rationalized based on
      a discrete fiber network model that relates model parameters with microstructural
      features of the tissues. Parameters were first determined for GC based on the
      quantity and organization of collagen fibers in the tissue. Next, parameters for
      HA were defined by comparing the microstructures of the two membranes, which
      differ in fiber organization in that collagen forms MUm-thick fiber bundles in GC
      while 50 nm-thin fibrils constitute the network in HA. The flexural behavior of
      these structures is phenomenologically represented in the model, indicating that
      shear forces are transmitted through fibrils within GC bundles, but to a much
      lesser extent than in a corresponding solid cross section. The model provides
      excellent predictions of the uniaxial and biaxial mechanical response, as well as
      of the progressive reorientation of fibers associated with uniaxial loading. The
      results are particularly relevant since model parameters were not obtained
      through a fitting procedure of the tissue's tension-stretch curve. Furthermore,
      simulations of representative in vivo deformation states indicated that a large
      part of the fibers are expected to be un-crimped under physiological loading
      conditions. Thus, the crimped shape of collagen fibers in the initial test
      configuration, and typically observed in histological analyses, might be a
      consequence of the contraction occurring when membranes are extracted from their
      environment in the body.

PMID- 28492653
TI  - Self-assembled core-polyethylene glycol-lipid shell nanoparticles demonstrate
      high stability in shear flow.
AB  - A core-polyethylene glycol-lipid shell (CPLS) nanoparticle consists of an
      inorganic core coated with polyethylene glycol (PEG) polymers, surrounded by a
      lipid bilayer shell. It can be self-assembled from a PEGylated core with surface
      tethered PEG chains, where all the distal ends are covalently bonded to lipid
      molecules. Upon adding free lipids, a complete lipid bilayer shell can be formed
      on the surface driven by the hydrophobic nature of lipid tails, leading to the
      formation of a CPLS nanoparticle. The stability of CPLS nanoparticles in shear
      flow has been systematically studied through large scale dissipative particle
      dynamics simulations. CPLS nanoparticles demonstrate higher stability and less
      deformation in shear flow, compared with lipid vesicles. Burst leakage of drug
      molecules inside lipid vesicles and CPLS NPs can be induced by the large pores at
      their tips. These pores are initiated by the maximum stress in the waist region.
      It further grows along with the tank-treading motion of vesicles or CPLS NPs in
      shear flow. However, due to the constraints applied by PEG polymers, CPLS NPs are
      less deformed than vesicles with comparable size under the same flow conditions.
      Thus, the less deformed CPLS NPs express a smaller maximum stress at waists,
      demonstrating higher stability. Pore formation at waists, evolving into large
      pores on vesicles, leads to the burst leakage of drug molecules and complete
      rupture of vesicles. In contrast, although similar drug leakage in CPLS
      nanoparticles can occur at high shear rates, pores initiated at moderate shear
      rates tend to be short-lived and close due to the constraints mediated by PEG
      polymers. This kind of 'self-healing' capability can be observed over a wide
      range of shear rates for CPLS nanoparticles. Our results suggest self-assembled
      CPLS nanoparticles to exhibit high stability during blood circulation without
      rapid drug leakage. These features make CPLS nanoparticles candidates for a
      promising drug delivery platform.

PMID- 28492655
TI  - Formation of modulated phases and domain rigidification in fatty acid-containing
      lipid membranes.
AB  - We investigated the phase behavior of lipid membranes containing fatty acids
      (FAs) by microscopy and differential scanning calorimetry. We used palmitic acid
      (saturated FA), oleic acid (cis-isomer of unsaturated FA), elaidic acid (trans
      isomer of unsaturated FA), and phytanic acid (branched FA) and examined the
      effects of FAs on phase-separated structures in lipid bilayer membranes
      consisting of dioleolylphosphocholine (DOPC)/dipalmitoylphosphocholine
      (DPPC)/cholesterol (Chol). Palmitic acid and elaidic acid exclude Chol from the
      DPPC-rich phase. As a result, the liquid-ordered phase formed by DPPC and Chol
      transforms into a solid-ordered phase. Oleic acid and phytanic acid significantly
      reduce the line tension at the liquid domain boundary. This decrease in line
      tension leads to the formation of modulated phases, such as striped, hexagonal,
      and polygonal domains. We measured the line tension and the interdomain
      interaction in these specific domains by an image analysis. The result showed
      that oleic acid and phytanic acid-containing vesicles as well as palmitic acid
      containing vesicles are not spherical, and this domain-induced deformation is
      explained theoretically.

PMID- 28492656
TI  - A study on one-step laser nanopatterning onto copper-hydrazone-complex thin films
      and its mechanism.
AB  - Semiconductor diode-based laser patterning with visible light has been
      extensively applied to the fabrication of arbitrary structures. However,
      recently, the technique has faced a great challenge because it cannot meet
      nanoscale-resolved patterning fabrication due to the optical diffraction limit,
      which is an inherent drawback in the field of optics. To attack the question,
      copper(ii)-hydrazone-complex (CuL2) thin films are used as laser patterning
      materials. Under the heating of a writing laser spot, one-step laser
      nanopatterning on the CuL2 thin films is obtained. The convex-type and concave
      type pattern structures are directly written without wet-etching and developing
      processes. The minimum pattern feature size is about 31 nm, which is far smaller
      than the diffraction limit and only ~1/20 the writing spot size. Analysis
      indicates that the laser nanopatterning originates from obvious photothermal
      localization responses to the writing spot. Compared with common organic resists,
      the exposure dose of CuL2 is several orders higher than that of the polymer; thus
      CuL2 thin film materials are suitable for maskless direct laser writing
      lithography. This work also provides an effective method for one-step
      nanopatternings through diode-based laser writing at visible light wavelengths.

PMID- 28492657
TI  - Outstanding Reviewers for Chemical Society Reviews in 2016.

PMID- 28492658
TI  - Interconnected macroporous 3D scaffolds templated from gelatin nanoparticle
      stabilized high internal phase emulsions for biomedical applications.
AB  - Here we report on the successful preparation of open-cellular macroporous 3D
      scaffolds templated from gelatin nanoparticle-stabilized HIPEs with acrylamide
      (AM) as the monomer in the continuous phase. Tuning the gelatin nanoparticle
      concentration or AM content led to different porous structures with void
      diameters varying between 30 and 78 MUm. More importantly, keeping HIPEs at room
      temperature to undergo a limited kinetic coarsening before polymerization could
      greatly improve the interconnectivity and pore size of the scaffolds, with the
      average diameters (approx. 118 MUm) being enlarged 1.5-fold. Additionally, the
      scaffolds had a character of soft tissue with compressive modulus more than 150
      kPa. The cell culture assay confirmed that HepG2 cells not only could adsorb on
      but also were grown inside the scaffolds, representing a characteristic of the
      good biocompatibility of the scaffolds. Our work suggests that the 3D scaffolds
      fabricated from gelatin nanoparticle-stabilized HIPE templates are promising
      culture substrates for a wide range of applications in the biomedical field.

PMID- 28492660
TI  - Selective vesicle aggregation achieved via the self-assembly of terpyridine-based
      building blocks.
AB  - Herein, we report the self-assembly of a mono terpyridine-based building block
      modified with long alkyl chains, which gives rise to vesicular aggregates in
      aqueous media. The vesicles are responsive to transition metal ions, and form
      different kinds of aggregates after metal-ligand coordination. In particular,
      Ni(ii) shows a unique influence on morphological transitions, whereby vesicles
      aggregate and fuse upon the addition of Ni(ii) ions. Spectroscopic and
      morphological studies are highlighted in this work. Furthermore, the formed
      vesicles could behave as a matrix for encapsulating fluorescent dyes with similar
      molecular structure via co-assembly, enabling more accurate observation of
      vesicle aggregation via confocal laser scanning techniques.

PMID- 28492659
TI  - Ensemble clustering of phosphoproteomic data identifies differences in protein
      interactions and cell-cell junction integrity of HER2-overexpressing cells.
AB  - Overexpression of HER2, a receptor tyrosine kinase of the ERBB family, in breast
      cancer is related to increased cancer progression and aggressiveness. A breast
      epithelial cell model with the single perturbation of HER2 overexpression is
      capable of replicating the increased aggressiveness of HER2 overexpressing
      cancers. In previous work, Wolf-Yadlin and colleagues (Wolf-Yadlin et al., Mol.
      Syst. Biol., 2006, 2) measured the proximal tyrosine phosphorylation dynamics of
      the parental and HER2 overexpressing cells (24H) in response to EGF. Here, we
      apply an ensemble clustering approach to dynamic phosphorylation measurements of
      the two cell models in order to identify signaling events that explain the
      increased migratory potential of HER2 overexpressing cells. The use of an
      ensemble approach for identifying relationships within a dataset and how these
      relationships change across datasets uncovers relationships that cannot be found
      by the direct comparison of dynamic responses in the two conditions. Of
      particular note is a drastic change in the clustering of SHC1 phosphorylation (on
      site Y349) from an EGFR-MAPK module in parental cells to a module consisting of
      an E-cadherin junction protein phosphorylation site, catenin delta-1 Y228, in
      HER2 overexpressing (24H) cells. Given the importance of E-cadherin junctions in
      healthy epithelial wound healing and migration, we chose to test the
      computationally-derived identification of altered cell junctions and CTNND1:SHC1
      relationships. Our cell and molecular biology experiments demonstrate that SHC
      and CTNND1 interact in an EGF- and HER2-dependent manner and that the cell
      junctions are phenotypically affected by HER2, breaking down in response to EGF
      and yet avoiding apoptosis as a result of cell junction loss. The results suggest
      a mechanism by which HER2 alters the localization of the SHC-MAPK signaling axis
      and a phenotypic effect on cell junction integrity.

PMID- 28492661
TI  - Improved catalysts for hydrogen evolution reaction in alkaline solutions through
      the electrochemical formation of nickel-reduced graphene oxide interface.
AB  - H2 production via water electrolysis plays an important role in hydrogen economy.
      Hence, novel cheap electrocatalysts for the hydrogen evolution reaction (HER) are
      constantly needed. Here, we describe a simple method for the preparation of
      composite catalysts for H2 evolution, consisting in simultaneous reduction of the
      graphene oxide film, and electrochemical deposition of Ni on its surface. The
      obtained composites (Ni@rGO), compared to pure electrodeposited Ni, show an
      improved electrocatalytic activity towards HER in alkaline media. We found that
      the activity of the Ni@rGO catalysts depends on the surface composition (Ni vs. C
      mole ratio) and on the level of structural disorder of the rGO support. We
      suggest that HER activity is improved via Hads spillover from the Ni particles to
      the rGO support, where quick recombination to molecular hydrogen is favored. A
      deeper insight into such a mechanism of H2 production was achieved by kinetic
      Monte-Carlo simulations. These simulations enabled the reproduction of
      experimentally observed trends under the assumption that the support can act as a
      Hads acceptor. We expect that the proposed procedure for the production of novel
      HER catalysts could be generalized and lead to the development of a new
      generation of HER catalysts by tailoring the catalyst/support interface.

PMID- 28492662
TI  - Giant magnetic anisotropy of rare-earth adatoms and dimers adsorbed by graphene
      oxide.
AB  - Nowadays, transition-metal adatoms and dimers with giant magnetic anisotropy have
      attracted much attention due to their potential applications in data storage,
      spintronics and quantum computations. Using density-functional calculations, we
      investigated the magnetic anisotropy of the rare-earth adatoms and dimers
      adsorbed by graphene oxide. Our calculations reveal that the adatoms of Tm, Er
      and Sm possess giant magnetic anisotropy, typically larger than 40 meV. When the
      dimers of (Tm,Er,Sm)-Ir are adsorbed onto graphene oxide, the magnetic anisotropy
      even exceeds 200 meV. The magnetic anisotropy can be tuned by the external
      electric field as well as the environment.

PMID- 28492663
TI  - A versatile microfluidic device for high throughput production of microparticles
      and cell microencapsulation.
AB  - Biocompatible microparticles are valuable tools in biomedical research for
      applications such as drug delivery, cell transplantation therapy, and analytical
      assays. However, their translation into clinical research and the pharmaceutical
      industry has been slow due to the lack of techniques that can produce
      microparticles with controlled physicochemical properties at high throughput. We
      introduce a robust microfluidic platform for the production of relatively
      homogeneous microdroplets at a generation frequency of up to 3.1 MHz, which is
      about three orders of magnitude higher than the production rate of a conventional
      microfluidic drop maker. We demonstrated the successful implementation of our
      device for production of biocompatible microparticles with various crosslinking
      mechanisms and cell microencapsulation with high cell viability.

PMID- 28492664
TI  - Size-tunable, highly sensitive microelectrode arrays enabled by polymer pen
      lithography.
AB  - By combining polymer pen lithography (PPL) patterning with in situ
      polymerization, we report a straightforward and bottom-up approach for bench-top
      fabrication of microelectrode arrays (MEAs) with well-controlled dimensions. The
      as-fabricated MEAs can be used to electrodeposit prussian blue in situ and work
      as a biosensor for H2O2 with a detection limit as low as 5 nM at a sensitivity of
      0.7 A cm-2 M-1.

PMID- 28492666
TI  - DNA-friendly Cu(ii)/TEMPO-catalyzed 5-hydroxymethylcytosine-specific oxidation.
AB  - The mixture of copper(ii) perchlorate and 2,2,6,6-tetramethylpiperidine-1-oxyl
      (TEMPO) mildly and specifically oxidized 5-hydroxymethylcytosine to yield 5
      formylcytosine because of its allyl alcohol specificity. The genomic DNA oxidized
      at 5-hydroxymethylcytosine by the copper(ii)/TEMPO oxidation was efficiently
      analyzed using various practical methods: DNA cleavage by piperidine, specific
      functionalization by hydrazone formation, and genome-wide high-resolution
      microarray.

PMID- 28492670
TI  - Dietary krill oil enhances neurocognitive functions and modulates proteomic
      changes in brain tissues of d-galactose induced aging mice.
AB  - The effects of dietary krill oil on neurocognitive functions and proteomic
      changes in brain tissues of d-galactose-induced aging mice were evaluated.
      Dietary krill oil enhanced the neurocognitive functions of aging mice with a
      significant (P < 0.05) decrease in escape latency and an increase in the number
      of times of crossing over the hidden platform during the Morris water maze test.
      Krill oil was also found to protect against oxidative damage, lipid peroxidation
      and neurodegenerative diseases. Oxidative stress biomarkers of aging mice
      administered with krill oil showed significant (P < 0.05) improvement with an
      increase in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      levels; there were insignificant changes in the serum malondialdehyde (MDA)
      level. In terms of proteomic changes, krill oil resulted in upregulation of the
      Celsr3 and Ppp1r1b gene expression, which contribute to brain development,
      learning and memory behavior processes. In particular, the Ppp1r1b gene is
      associated with the inhibition of dopamine releases, which decreases the
      motivation for learning.

PMID- 28492674
TI  - A phenazine-barbituric acid based colorimetric and ratiometric near-infrared
      fluorescent probe for sensitively differentiating biothiols and its application
      in TiO2 sensor devices.
AB  - A new colorimetric and ratiometric near-infrared fluorescent probe based on
      phenazine-barbituric acid was developed to ultrasensitively detect biothiols. The
      favorable ratiometric changes helped the imaging and differentiation of Cys in
      living cells. Besides, the probe was successfully employed to construct TiO2
      sensor devices, which could quantify Hcy concentration in serum.

PMID- 28492676
TI  - A programmed terminal extension strategy to light up multiple beacons for DNA and
      cellular telomerase detection.
AB  - Here we develop a new method for the sensitive detection of DNA and cellular
      telomerase using an enzyme-triggered terminal extension strategy that the
      produced strand can light up multiple beacons on the surface of gold
      nanoparticles.

PMID- 28492680
TI  - Rare event simulations reveal subtle key steps in aqueous silicate condensation.
AB  - A replica exchange transition interface sampling (RETIS) study combined with Born
      Oppenheimer molecular dynamics (BOMD) is used to investigate the dynamics,
      thermodynamics and the mechanism of the early stages of the silicate condensation
      process. In this process, two silicate monomers, of which one is an anionic
      species, form a negatively charged five-coordinated silicate dimer. In a second
      stage, this dimer can fall apart again, forming the original monomers, or release
      a water molecule into the solution. We studied the association and dissociation
      reaction in the gas phase, and the dissociation and water removal step in the
      aqueous phase. The results on the aqueous phase dissociation suggest two possible
      mechanisms. The breakage of the bond between the intermediate oxygen and the five
      coordinated silicon is sometimes accompanied by a proton transfer. After
      dissociation into silicate monomers, the anionic monomer is either the previously
      four-coordinated silicon or the previously five-coordinated silicon depending on
      whether the hydrogen transfer occurs or not. Our results show that the mechanism
      of proton transfer is highly predominant. Water removal simulations also show two
      possible mechanisms distinguished by the proton transfer reaction path. Proton
      transfer can occur either via a direct or via a water mediated reaction step. The
      calculations reveal that although both mechanisms contribute to the water removal
      process, the direct proton transfer is slightly favorable and occurs roughly in
      six out of ten occasions.

PMID- 28492681
TI  - Statistical modelling and simulation of nanohybrid shish-kebab architecture of PE
      b-PEG copolymers and carbon nanotubes.
AB  - Carbon nanotubes have been known to develop hierarchically ordered polymer
      nanocomposites by virtue of epitaxial crystallization. A unique product of CNT
      induced crystallization is generation of nanohybrid shish-kebab (NHSK) structure,
      which has gained tremendous attention owing to its unique applications. However,
      research faces major challenges in terms of producing tunable patterns on CNTs,
      which are largely governed by precise control of the crystallization parameters.
      Conventional methods of experimentation can mislead the effect of experimental
      conditions on NHSK structure. The effect of crystallization time, undercooling
      temperature and polymer concentration on the NHSK architecture of carbon
      nanotubes (CNTs) and on a block copolymer, polyethylene-b-polyethylene glycol (PE
      b-PEG), was studied in this work by applying the Response Surface Methodology
      (RSM). The present novel investigation mainly reports the statistical models that
      can be used to predict the different NHSK structural features such as diameter,
      periodicity, and thickness by including the interaction and quadratic effects of
      experimental variables. The developed models are in very good agreement with the
      experimental data and are statistically significant. Our novel approach can be
      used to better understand the interplay between various crystallization
      parameters for periodic patterning on carbon nanotubes to generate tunable
      hierarchical structures.

PMID- 28492682
TI  - Scaling description of non-local rheology.
AB  - The plastic flow of amorphous materials displays non-local effects, characterized
      by a cooperativity length scale xi. We argue that these effects enter in the more
      general description of surface phenomena near critical points. Using this
      approach, we obtain a scaling relation between exponents that describe the strain
      rate profiles in shear driven and pressure driven flow, which we confirm both in
      numerical models and experimental data. We find empirically that the cooperative
      length follows closely the characteristic length previously extracted in
      homogenous bulk flows. This analysis shows that the often used mean field
      exponents fail to capture quantitatively the non-local effects. Our analysis also
      explains the unusually large finite size effects previously observed in pressure
      driven flows.

PMID- 28492684
TI  - Oxidative remediation of 4-methylcyclohexanemethanol (MCHM) and propylene glycol
      phenyl ether (PPh). Evidence of contaminant repair reaction pathways.
AB  - A large spill of 4-methylcyclohexanemethanol (MCHM) and propylene glycol phenyl
      ether (PPh) into the Elk River near Charleston, West Virginia on January 9, 2014
      led to serious water contamination and public concerns about appropriate
      remediation. To assess the feasibility of advanced oxidation processes (AOPs) for
      remediation of waters contaminated with these compounds, we induced hydroxyl
      radical (HO) reactions using time-resolved and steady-state radiolysis methods.
      Detailed product analyses showed initial HO attack was at the benzene ring of
      PPh, and occurred through H-atom abstraction reactions for MCHM. Pulse radiolysis
      and steady state radiolysis experiments conducted using pure compound solutions,
      mixtures of the compounds and real water solvents allowed us to obtain
      mechanistic insights of hydroxyl radical attack and establish the fate of the
      compounds using AOP remediation technologies. These results demonstrate that
      hydroxyl radical induced oxidization of PPh can lead to "repair-type" reactions,
      which regenerates this contaminant. The study further highlights the importance
      of such counterproductive reactions for the quantitative estimate of the required
      amount of oxidant in any large-scale treatment approaches.

PMID- 28492685
TI  - Crystal chemistry of Mg substitution in NaMnPO4 olivine: concentration limit and
      cation distribution.
AB  - Metal ion substitution in phospho-olivines is an effective way to improve their
      performance as electrode materials in lithium ion and alternative sodium ion
      batteries. In this contribution, we examine in detail the crystal structure of Mg
      substituted NaMnPO4. The preferential occupancy of the alkaline M1 position by
      Mg2+ ions has been found for the first time - a phenomenon which appears to be
      opposite to the case of Mg-substituted LiMnPO4, where Mg2+ and Mn2+ reside in the
      M2 position. Mg solubility in NaMnPO4 is limited in the range of 0.10 < Mg/(Mg +
      Mn) < 0.15 mole part. Mg-substituted NaMnPO4 is prepared at 200  degrees C by
      ionic exchange reactions involving the participation of mixed dittmarite salts,
      KMn1-xMgxPO4.H2O. The structural aspects of Mg substitution in NaMnPO4 are
      studied by combination of powder X-ray diffraction using the Rietveld analysis
      with IR and electron paramagnetic resonance spectroscopy. The morphologies of
      precursors and target olivines are examined by means of SEM and EDS. In order to
      understand the crystal chemistry of Mg-substituted NaMnPO4, we use solid
      solutions between LiMnPO4 and LiMgPO4 as references. The reference compositions
      of LiMn1-xMgxPO4 are prepared using the same KMn1-xMgxPO4.H2O precursors as in
      the case of Mg-substituted NaMnPO4.

PMID- 28492687
TI  - Packing arrangement of 13C selectively labeled sequence model peptides of Samia
      cynthia ricini silk fibroin fibers studied by solid-state NMR.
AB  - Samia cynthia ricini (S. c. ricini) is one of the wild silkworms. Their silk
      fibroins have been paid attention as potentially valuable biomedical materials as
      well as Bombyx mori silk fibroins, but detailed information on the packing
      arrangement of the fibers is still not currently well understood at a molecular
      level. In this study, 34 mer model peptides, GGAGGGYGGDGG(A)12GGAGDGYGAG with
      different 13C labeled positions have been synthesized as a typical sequence of
      the primary structure of S. c. ricini silk fibroins made up of tandemly repeated
      sequences of polyalanine as the crystalline region and glycin-rich sequences as
      the non-crystalline region. The heterogeneous structure was obtained from the
      determination of the fraction of several conformations depending on the position
      of the Ala residue by 13C cross polarization/magic angle spinning NMR. The
      packing arrangement was studied by 13C dipolar assisted rotational resonance NMR
      and packing in a staggered arrangement rather than a rectangular arrangement of
      this peptide with an anti-parallel beta-sheet structure was clarified, which is
      in good agreement with our previous report on the packing arrangement of (Ala)7
      with an anti-parallel beta-sheet structure.

PMID- 28492688
TI  - Low energy electron attenuation lengths in core-shell nanoparticles.
AB  - A velocity map imaging spectrometer is used to measure photoemission from free
      core-shell nanoparticles, where a salt core is coated with a liquid hydrocarbon
      shell (i.e. squalane). By varying the radial thickness of the hydrocarbon shell,
      electron attenuation lengths (EALs) are determined by measuring the decay in
      photoemission intensity from the salt core. In squalane, electrons with kinetic
      energy (KE) above 2 eV are found to have EALs of 3-5 nm, whereas electrons with
      smaller KE (<2 eV) have significantly larger EALs of >15 nm. These results (in
      the context of other energy-resolved EAL measurements) suggest that the energy
      dependent behavior of low energy electrons is similar in dielectrics when KE > 2
      eV. At this energy the EALs do not appear to exhibit strong energy dependence.
      However, at very low KE (<2 eV), the EALs diverge and appear to be extremely
      material dependent.

PMID- 28492689
TI  - Interconnected LiCuVO4 networks with in situ Cu generation as high-performance
      lithium-ion battery anode.
AB  - Interconnected LiCuVO4 networks were synthesized through a facile surfactant
      assisted approach. Detailed investigations on the lithium storage mechanism
      manifest that metallic Cu nanoparticles are generated in situ during the first
      discharge process and remain mostly intact in the following cycles, thereby
      enhancing conductivity of the electrode. The interconnected networks with
      submicron sized primary particles endow the LiCuVO4 with a large amount of active
      sites and thus high capacitive charge storage. Benefiting from a peculiar
      structure, the resultant interconnected LiCuVO4 networks deliver extraordinary
      rate performance (216 mA h g-1 up to 10 A g-1) and ultralong cycling stability
      (~85% capacity retention after 5000 cycles at 5 A g-1). The exceptional rate
      performance and cycling stability show that the interconnected LiCuVO4 networks
      possess great potential for lithium-ion batteries.

PMID- 28492690
TI  - Coordination nanosheets (CONASHs): strategies, structures and functions.
AB  - Nanosheets, which are two-dimensional polymeric materials, remain among the most
      actively researched areas of chemistry and physics this decade. Generally,
      nanosheets are inorganic materials created from bulk crystalline layered
      materials and have fascinating properties and functionalities. An emerging
      alternative is molecule-based nanosheets containing organic molecular components.
      Molecule-based nanosheets offer great diversity because their molecular, ionic,
      and atomic constituents can be selected and combined to produce a wide variety of
      nanosheets. The present article focuses on coordination nanosheets (CONASHs), a
      class of molecule-based nanosheets comprising organic ligand molecules and metal
      ions/atoms in a framework linked with coordination bonds. Following the
      Introduction, Section 2 describes CONASHs, including their definition, design,
      synthetic procedures, and characterisation techniques. Section 3 introduces
      various examples of CONASHs, and Section 4 explores their functionality and
      possible applications. Section 5 describes an outlook for the research field of
      CONASHs.

PMID- 28492691
TI  - Binding groups for highly ordered SAM formation: carboxylic versus thiol.
AB  - The structure of analogous SAMs chemisorbed on an Ag substrate via a -SH or -COOH
      binding group is reported. Our observations indicate that COOH binding groups can
      be considered as a promising alternative for the current standard based on the
      sulfur binding groups, particularly when 2D ordering, SAM fabrication time and
      stability under ambient conditions are of great importance.

PMID- 28492692
TI  - Pharmacokinetics of table and Port red wine anthocyanins: a crossover trial in
      healthy men.
AB  - This study was designed to evaluate the pharmacokinetics of Port and table red
      wine anthocyanins in healthy men. Volunteers were recruited to drink 250 mL of a
      table red wine (221 mg of anthocyanins) and 150 mL of young Port red wine (49 mg
      of anthocyanins). Venous blood was collected from participants at 0, 15, 30, 60
      and 120 min after wine ingestion. Urine samples were collected at baseline and at
      120 min. Anthocyanins and anthocyanin metabolites in plasma and urine samples
      were quantified by HPLC-DAD and tentatively identified by LC-MS. Red wine
      anthocyanins were detected in their intact forms in both plasma and urine
      samples, but the glucuronylated metabolites of peonidin and malvidin (PnGlucr and
      MvGlucr) were the two main derivatives detected after both red wine consumptions.
      For the first time, and supported by the synthesis of Mv3Glucr, the main pathway
      followed by Mv3glc after absorption was described and involves anthocyanidin
      conjugation with glucuronic acid after glucose removal. Despite the lower total
      content of anthocyanins ingested when volunteers drank Port wine, no differences
      were observed in the plasma Cmax of MvGlucr and PnGlucr after table and Port red
      wine consumption. The relative bioavailability of anthocyanins in Port wine was
      96.58 +/- 5.74%, compared to the anthocyanins present in red wine. In conclusion,
      both Port and table red wines are good sources of bioavailable anthocyanins.

PMID- 28492693
TI  - Nickel catalyzed enantioselective hydroarsination of nitrostyrene.
AB  - A catalytic asymmetric hydroarsination reaction of an activated alkene viz. (E)
      nitrostyrene was developed using chiral PCP Pt-, Pd- and Ni-pincer complexes as
      catalysts. The corresponding chiral tertiary arsine adduct was obtained in ees of
      up to 80% under mild reaction conditions using the PCP Ni-Cl pincer catalyst. The
      arsine adduct was furnished with catalyst loadings of 1-5 mol% and the reaction
      duration ranging from <5 min to 180 min. The subsequent coordination of the
      hydroarsination product to gold(i) chloride allowed for the confirmation of the
      stereochemistry of the arsine adduct via crystallographic analysis.

PMID- 28492694
TI  - Tuning the electronic properties of monolayer and bilayer transition metal
      dichalcogenide compounds under direct out-of-plane compression.
AB  - The band-gap modulation of atomically thin semiconductor transition metal
      dichalcogenides (MX2; M = Mo or W, X = S or Se) under direct out-of-plane
      compression is systematically studied by means of the density functional theory
      (DFT) formalism including spin-orbit coupling (SOC) and dispersion correction
      (D3). The out-of-plane compared with other regimes stress regime significantly
      reduces the pressure threshold at which the semimetal state is achieved (2.7-3.1
      and 1.9-3.2 GPa for mono- and bilayer systems, respectively). Structural,
      electronic and bonding properties are investigated for a better understanding of
      the electronic transitions achieved with compression. A notable relationship with
      the formal ionic radius (M4+ and X2-) is obtained. On one hand, the monolayer
      systems with the smallest transition metal radius (Mo4+ < W4+) reach the
      semimetal state at lower stress, on the other hand, for bilayer specimens the
      transition to semimetal is observed earlier for compounds with the smallest
      chalcogenide radius (S2- < Se2-). Moreover, the appearance of non-covalent
      interaction (NCI) domains in the semimetal state confirms that the out-of-plane
      compression promotes the interaction between sulfur atoms in the single layered
      systems and reduces the interlayer space in bilayer configurations. Our
      predictions, supported by experimental evidences in the case of monolayered MoS2,
      demonstrate new alternative methods for tuning the electronic properties of
      transition metal dichalcogenides under direct out-of-plane compression.

PMID- 28492695
TI  - Joint assessment in von Willebrand disease. Validation of the Haemophilia Joint
      Health score and Haemophilia Activities List.
AB  - Assessment of clinical outcome after joint bleeding is essential to identify
      joint damage and optimise treatment, to prevent disability. However, disease
      specific tools to assess the musculoskeletal status in patients with von
      Willebrand disease (VWD) are lacking. We aimed to determine validity and
      reliability of the Haemophilia Joint Health Score (HJHS) and Haemophilia
      Activities List (HAL) in patients with Von Willebrand disease (VWD). Ninety-six
      patients with VWD were included (mean age 46 years) of whom 27 had more than five
      documented joint bleeds. The HJHS was performed in all patients and all patients
      completed the HAL and Impact on Participation and Autonomy (IPA) questionnaires.
      Health-related quality of life (SF36) results were obtained from the prior
      'Willebrand in the Netherlands' study. Joint X-rays of knees, elbows and ankles
      were scored according to Pettersson (PS). Internal consistency of the HJHS
      (Cronbach's alpha (alpha)=0.75) and HAL (alpha=0.89) were good. Inter-observer
      agreement of the HJHS was good (ICC 0.84; Limits of Agreement +/- 10.3). The HJHS
      showed acceptable correlation with the X-ray PS (Spearman's r (rs)>0.60 all
      joints) and HAL (rs=0.71). The HAL also showed acceptable correlation with the
      SF36 physical functioning (rs=0.65) and IPA (rs=0.69). Hypothesis testing showed
      adequate discriminative power of both instruments: in patients with a history of
      >5 versus <= 5 joint bleeds (median HJHS 10 vs 2 (p<0.01); median HAL 77 vs 98
      (p<0.01)), independent from age. In conclusion, both the HJHS and HAL are
      feasible to assess clinical outcome after joint bleeds in VWD.

PMID- 28492696
TI  - Complex recombination with deletion in the F8 and duplication in the TMLHE
      mediated by int22h copies during early embryogenesis.
AB  - Haemophilia A (HA) is a common X-linked recessive bleeding disorder and almost
      one half of patients with severe HA are caused by intron 22 inversion (Inv22) in
      the F8. Inv22 is considered to be almost exclusively of meiotic origin in germ
      cells during spermatogenesis and only one mosaic Inv22 female carrier with the
      mutation possibly occurring during mitosis of the embryo has been reported so
      far. Previously we have identified a novel complex recombination mediated by
      int22h copies in a sporadic severe HA pedigree and herein we have localised the
      sequences flanking the breakpoint region using genome walking technique, AccuCopy
      technique, gene chip and real-time PCR. The disease causing genetic variant
      registered an 18.1 kb deletion including part of int22h-1 through the intron 23
      of F8 and a 113.3 kb duplication of part of int22h-2 through the intron 1 of
      TMLHE inserted in the religated region of the F8. Two intrinsically linked
      mechanisms of recombination-dependent DNA replication: microhomology-mediated
      break-induced replication (MMBIR) followed by break-induced replication (BIR)
      might be responsible for the incident of the complex recombination during early
      embryogenesis of the proband's mother.

PMID- 28492697
TI  - CD32 inhibition and high dose of rhFVIII suppress murine FVIII-specific recall
      response by distinct mechanisms in vitro.
AB  - Development of neutralising antibodies (inhibitors) against factor VIII (FVIII)
      is a frequent and severe complication of replacement therapy in haemophilia A.
      Previous data from haemophilia A mouse model demonstrates that both CD32
      inhibition and high doses of rhFVIII prevent the differentiation of FVIII
      specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here,
      cellular targets responsible for the suppression of ASC formation by means of
      CD32 inhibition and high dose of rhFVIII were analysed. We investigated apoptosis
      on FVIII-specific MBCs using a pan caspases inhibitor, and screened for defects
      in rhFVIII presentation by analysing T cell release of Th1- and Th2-cytokines in
      vitro. Although high dose of rhFVIII suppressed ASC formation, cytokine response
      was not affected. Upon re-stimulation of splenocytes with high dose of rhFVIII,
      prevention of apoptosis fully restored the FVIII-specific recall response. In
      contrast, genetic deletion or inhibition of CD32 significantly altered Th1- and
      Th2-response. CD32 blockade and inhibition of apoptosis resulted in a partial
      rescue of FVIII-specific ASCs. Normal cytokine secretion could not be restored.
      In conclusion, suppression of FVIII-specific recall response by CD32 and high
      doses of rhFVIII is mediated by distinct mechanisms. High dose of rhFVIII induces
      apoptosis in FVIII-specific MBCs but does not influence FVIII-specific T cell
      response. CD32 blockade, however, may suppress the FVIII-specific recall response
      by two ways: i) increasing apoptosis of FVIII-specific MBCs and ii) disturbing
      FVIII-specific T cell response by modulating presentation of rhFVIII to CD4+ T
      cells in vitro.

PMID- 28492698
TI  - IL-33 stimulates the release of procoagulant microvesicles from human monocytes
      and differentially increases tissue factor in human monocyte subsets.
AB  - Monocytes and monocyte-derived microvesicles (MVs) are the main source of
      circulating tissue factor (TF). Increased monocyte TF expression and increased
      circulating levels of procoagulant MVs contribute to the formation of a
      prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33
      is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory
      diseases, but its role in regulating thrombosis is still unclear. The aim of the
      present study was to investigate the effects of IL-33 on the procoagulant
      properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and
      concentration-dependent increase of monocyte TF mRNA and protein levels via
      binding to the ST2-receptor and activation of the NF-kappaB-pathway. The IL-33
      treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the
      TF activity of both the isolated monocytes and monocyte-derived MVs. The
      monocytes were classified into subsets according to their CD14 and CD16
      expression. Intermediate monocytes (IM) showed the highest ST2 receptor
      expression, followed by non-classical monocytes (NCM), and classical monocytes
      (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a
      tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma
      levels of IL-33 were positively correlated with CD14+TF+ MVs in patients
      undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide
      novel evidence that the proinflammatory cytokine IL-33 induces differential TF
      expression and activity in monocyte subsets, as well as the release of
      procoagulant MVs. In this manner, IL-33 may contribute to the formation of a
      prothrombotic state characteristic for cardiovascular disease.

PMID- 28492699
TI  - Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over
      production.
AB  - The effect of lipopolysaccharide (LPS) on platelet aggregation is still
      controversial. We performed in vitro and ex vivo studies in controls and in
      patients with community-acquired pneumonia (CAP) to assess the effect of LPS on
      platelet activation (PA). LPS (15-100 pg/ml) significantly increased PA only if
      combined with sub-threshold concentrations (STC) of collagen or ADP; this effect
      was associated with increased platelet H2O2 production, Nox2 activation, PLA2
      phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2alpha-III, and was inhibited by
      aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide
      (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and
      PLA2 activation demonstrated that LPS-mediated PA was associated with
      phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP
      patients serum endotoxins were significantly higher compared to 10 controls (145
      [115-187] vs 18 [6-21] pg/ml; p<0.01). Ex vivo study showed that agonist
      stimulated platelets were associated with enhanced PA (p<0.01), Toll-like
      receptor 4 (TLR4) expression (p<0.05), TxA2 (p<0.01) and 8-iso-PGF2alpha-III
      (p<0.01) production in CAP patients compared to controls. The study provides
      evidence that LPS amplifies the platelet response to common agonists via TLR4
      mediated eicosanoid production and suggests LPS as a potential trigger for PA in
      CAP.

PMID- 28492700
TI  - Coagulation factor XI improves host defence during murine pneumonia-derived
      sepsis independent of factor XII activation.
AB  - Bacterial pneumonia, the most common cause of sepsis, is associated with
      activation of coagulation. Factor XI (FXI), the key component of the intrinsic
      pathway, can be activated via factor XII (FXII), part of the contact system, or
      via thrombin. To determine whether intrinsic coagulation is involved in host
      defence during pneumonia and whether this is dependent on FXII activation, we
      infected in parallel wild-type (WT), FXI knockout (KO) and FXII KO mice with two
      different clinically relevant pathogens, the Gram-positive bacterium
      Streptococcus pneumoniae and the Gram-negative bacterium Klebsiella pneumoniae,
      via the airways. FXI deficiency worsened survival and enhanced bacterial
      outgrowth in both pneumonia models. This was accompanied with enhanced
      inflammatory responses in FXI KO mice. FXII KO mice were comparable with WT mice
      in Streptococcus pneumoniae pneumonia. On the contrary, FXII deficiency improved
      survival and reduced bacterial outgrowth following infection with Klebsiella
      pneumoniae. In both pneumonia models, local coagulation was not impaired in
      either FXI KO or FXII KO mice. The capacity to phagocytose bacteria was impaired
      in FXI KO neutrophils and in human neutrophils where activation of FXI was
      inhibited. Deficiency for FXII or blocking activation of FXI via FXIIa had no
      effect on phagocytosis. Taken together, these data suggest that FXI protects
      against sepsis derived from Streptococcus pneumoniae or Klebsiella pneumoniae
      pneumonia at least in part by enhancing the phagocytic capacity of neutrophils by
      a mechanism that is independent of activation via FXIIa.

PMID- 28492701
TI  - Short-term intensive training attenuates the exercise-induced interaction of mono
      1/2 cells and platelets after coronary bypass in cardiac patients.
AB  - The interaction between platelets and monocytes plays a critical role in the
      pathogenesis and progression of cardiovascular diseases. This study investigated
      how short-term intensive training (SIT) influences monocyte subset
      characteristics and exercise-induced monocyte and platelet aggregates (MPAs)
      following elective coronary bypass (CABG) in cardiac patients. Forty-nine
      patients hospitalised for CABG were randomised into SIT (N=26) and conventional
      training (CT, N=23) groups. The SIT subjects underwent supervised aerobic
      training at 80~120 % of the ventilatory anaerobic threshold based on sub-maximal
      exercise tests performed 7 days post-CABG for 20 sessions with two sessions/day
      and 30 min/session, which were completed within four weeks after surgery. The CT
      subjects performed light-intensity conditioning exercise for <=4 sessions.
      Resting and maximal exercise-mediated monocyte characteristics and MPA were
      determined before and following intervention. The SIT group had a larger
      improvement in ventilation efficiency and anaerobic threshold than the CT group;
      the SIT group exhibited larger reductions in blood monocyte subtypes 1 and 2
      (Mono1 and 2) counts at rest than the CT group; the SIT group but not the CT
      group exhibited attenuated formation of Mono1/platelet hetero-aggregation (MPA1)
      and CD42b expression on Mono1/2 caused by strenuous exercise; and plasma levels
      of macrophage inflammatory protein-1beta and soluble P-selectin showed similar
      trends as Mono1/2 and MPA1, respectively. In conclusion, SIT modestly improved
      aerobic capacity in patients following CABG. Moreover, SIT simultaneously
      ameliorated the CD42b expression of Mono1/2 cells and maximal exercise-induced
      MPA1, which may reduce the risk of inflammatory thrombosis.

PMID- 28492702
TI  - Low plasma FVII:C and activated FVII as predictive markers for overt disseminated
      intravascular coagulation.
AB  - In sepsis, binding of factor VII (FVII:C) and activated factor VII (FVIIa) with
      tissue factor is the key step of coagulation resulting in disseminated
      intravascular coagulation (DIC). We conducted a prospective cohort study among 47
      septic patients, aged 8 months to 18.8 years. They were initially divided into
      three groups of no DIC (n=27), non-overt DIC (n=14) and overt DIC (n=6). Blood
      samples were collected at 0, 24 and 48 hours (h) after the onset of sepsis. At
      the onset of sepsis, FVII:C tended to be lower in the non-overt DIC [median 57 %
      (interquartile range [IQR] 41-80)] and overt DIC groups [33 % (23-52)] than that
      in the no DIC group [65 % (44-87)]. Whereas FVIIa tended to be lower in the overt
      DIC group [1.29 % (0.50-4.19)] than those in the non-overt DIC [3.01 % (1.01
      5.24)] and no DIC groups [2.49 % (1.14-3.13)]. At 24 h, FVII:C was significantly
      lower in the non-overt DIC [57 % (41-101)] and overt DIC groups [31 % (28-49)]
      than that in the no DIC group [83 % (70-102)]. While FVIIa was significantly
      lower in the overt DIC group [2.15 % (0.86-3.96)] than that in the no DIC group
      [3.83 % (2.90-5.46)]. Using FVII:C <65 % or FVIIa <3 % at 24 h among patients
      without hepatic dysfunction to determine overt DIC at 24 h, the sensitivity was
      83.9 % and 77.4 %, respectively, and the specificity was both 83.3 %. Patients
      with low FVII:C and low FVIIa at 24 h after the onset of sepsis had a 20.8-fold
      (95 % confidence interval [CI], 2.0-213.0, p=0.010) and 14.4-fold (95 %CI, 1.5
      142.4, p=0.023) chance of overt DIC.

PMID- 28492703
TI  - Prehispanic (Guanches) mummies and natrium salts in burial caves of Las Canadas
      del Teide (Tenerife).
AB  - ABSTRACT: The prehispanic population of Tenerife (Guanches) buried their dead in
      caves. Many corpses are totally or partially mummified. Embalming procedures are
      largely unknown, besides some information recorded by chroniclers and the general
      idea that environmental conditions in some areas may favour natural
      mummification. Detailed observation of burial caves containing mummified corpses
      revealed the presence of a white mineral in form of crusts or powder that was not
      present in the vast majority of non-burial caves, especially in basaltic and
      trachybasaltic lava flows. We analysed these crusts and they consist of natrium
      carbonate salts. Therefore, we conducted a search visiting 30 caves, 3 of them
      harbouring mummified corpses, and made analyses if there were natrium salts in
      these caves and their amount. One burial cave was located in trachyphonolitic
      lava flow, and two further caves in trachybasaltic and basaltic lava flows. There
      was a significant association between presence of natrium salts and use of the
      cave as a burial site (chi2 = 9.37; p = 0.0259). The semiquantitatively assessed
      amount of natrium salts was also by far higher in burial caves than in non-burial
      ones (Z = 2.58, p = 0.01). There are no reports that support the use of natrium
      salts in the embalming process among the Guanches, but we found a clear-cut
      relationship between the presence and/or amount of natrium salts in caves and
      their use as burial sites by the prehispanic population buried in the central
      highlands, suggesting an intentional use of caves containing this mineral as
      burial caves, based perhaps on the observation of the ability of natrium salts to
      preserve corpses.

PMID- 28492704
TI  - Effectiveness of a school-based intervention to reduce the prevalence of
      overweight and obesity in children aged 7-11 years from Poznan (Poland).
AB  - ABSTRACT: The epidemic of obesity, which is one of the most important public
      health problems, appeared paradoxically as a result of improving living
      conditions. The aim of this study was to determine the effects on
      overweight/obesity prevalence of the primary-school-based intervention program.
      The group of 5,293 children (7-11 year-olds) from Poznan (Poland) was divided
      into two subgroups: experimental and control one. The research group was
      participating in extra physical activities. Measurements (height and weight) were
      taken twice: at baseline and after 1-year follow-up. The estimations of the
      prevalence of overweight/obesity were based on the cut-off points of the IOTF
      values. To estimate the risk the odds ratio (OR) were calculated. There were no
      differences in BMI for both boys and girls. Also there were no significant
      differences in prevalence of overweight and obesity, for both sexes. The risk of
      being overweight/obese was not reduced in children in the experimental group - OR
      for boys was 0.93 (0.80, 1.08), and for girls OR = 0.88 (0.76, 1.03). In
      conclusion, the risk of overweight/obesity has not changed after one year of
      extra physical activities and engagement in health-oriented education program.
      This study shows that in case of such programs it is necessary to apply more
      intense interventions, probably also during longer period of time. It is possible
      that other adverse factors have a stronger influence on the body mass, which
      would suggest that the theoretical part of intervention concerning pro-health
      related behaviors was not implemented in practice.

PMID- 28492705
TI  - Race, health, and discrimination: historical and contemporary perspectives from
      Brazil and the United States.

PMID- 28492706
TI  - Confronting racism in health services.

PMID- 28492707
TI  - The strangest of all encounters: racial and ethnic discrimination in US health
      care.
AB  - In 2003, a Committee of the Institute of Medicine of the National Academy of
      Sciences summarized hundreds of studies documenting that US racial minorities,
      especially African Americans, receive poorer quality health care for a wide
      variety of conditions than their White counterparts. These racial differences in
      health care persist after controlling for sociodemographic factors and patients'
      ability to pay for care. The Committee concluded that physicians' unconscious
      negative stereotypes of African Americans, and perhaps other people of color,
      likely contribute to these health care disparities. This paper selectively
      reviews studies published after 2003 on the likely contribution of physicians'
      unconscious bias to US health care disparities. All studies used the Implicit
      Association Test which quantifies the relative speed with which individuals
      associate positive attributes like "intelligent" with Whites compared to Blacks
      or Latino/as. In addition to assessing physicians' unconscious attitudes toward
      patients, some studies focused on the behavioral and affective dimensions of
      doctor-patient communication, such as physicians' "verbal dominance" and whether
      patients felt respected. Studies reviewed found a "pro-white" unconscious bias in
      physicians' attitudes toward and interactions with patients, though some evidence
      suggests that Black and female physicians may be less prone to such bias. Limited
      social contact between White physicians and racial/ethnic minorities outside of
      medical settings, plus severe time pressures physicians often face during
      encounters with patients who have complex health problems could heighten their
      susceptibility to unconscious bias.

PMID- 28492708
TI  - Shadows of doubt: the uneasy incorporation of identification science into legal
      determination of paternity in Brazil.
AB  - The arrival of DNA paternity testing in the 1980s was met with great enthusiasm
      in the Brazilian courts. Yet, over the past two decades, Brazilian legal doctrine
      and jurisprudence have increasingly rejected DNA proof as the sine qua non for
      paternity cases. Instead, DNA paternity testing has generated mountains of
      litigation, as biological proof has been challenged by the argument that
      paternity is primarily "socio-affective". Leading family law specialists describe
      this new conception of paternity as an outcome of the "revolutionary" provisions
      of the 1988 Constitution, which recognizes the "pluralism" of family forms in
      modern society and guarantees equal family rights for all children. Without
      denying the significance of the constitution's dignitary framework, we show that
      new legal understandings of paternity represent less a paradigm shift than a
      continuation of longstanding historical tensions between biological and socio
      cultural understandings of family and identity. In this article, we explore the
      development of biological and eventually genetic typing in Brazil, both of which
      had ties to the fields of criminology and race science. Our review suggests that
      techniques of biological identification, no matter how sophisticated or precise,
      were ineffective means for establishing identity, whether of individual
      personhood, as in the case of paternity, or national make-up. Instead, they
      became incorporated as supplemental methods into complex legal, social, and
      cultural decision-making around families.

PMID- 28492709
TI  - Differential reporting of discriminatory experiences in Brazil and the United
      States.
AB  - There has been little cross-national comparison of perceived discrimination, and
      few studies have considered how intersectional identities shape perception of
      discriminatory treatment in different societies. Using data from the ELSA-Brasil,
      a study of Brazilian civil servants, and the Americans' Changing Lives Study, a
      nationally-representative sample of U.S. adults, we compare reports of lifetime
      discrimination among race-by-gender groups in each society. We also consider
      whether educational attainment explains any group differences, or if differences
      across groups vary by level of education. Results reveal higher lifetime
      discrimination experiences among Black respondents in both countries, especially
      Black men, than among Whites, and lower reports among White women than White men.
      Brown men and women also reported higher levels than White men in Brazil. For all
      race-by-gender groups in both countries, except Brazilian White men, reports of
      discrimination were higher among the more educated, though adjusting for
      educational differences across groups did not explain group differences. In
      Brazil, we found the greatest racial disparities among the college educated,
      while U.S. Black men were more likely to report discrimination than White men at
      all levels of education. Results reveal broad similarities across countries,
      despite important differences in their histories, and an intersectional approach
      contributed to identification of these similarities and some differences in
      discrimination experiences. These findings have implications for social and
      public health surveillance and intervention to address the harmful consequences
      of discrimination.

PMID- 28492710
TI  - Race and U.S. medical experimentation: the case of Tuskegee.

PMID- 28492711
TI  - CURCUMIN IN COMBINATION WITH TRIPLE THERAPY REGIMES AMELIORATES OXIDATIVE STRESS
      AND HISTOPATHOLOGIC CHANGES IN CHRONIC GASTRITIS-ASSOCIATED HELICOBACTER PYLORI
      INFECTION.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) gastric infection is a main cause of
      inflammatory changes and gastric cancers. OBJECTIVE: The aim of this study was
      finding the effects of curcumin on oxidative stress and histological changes in
      chronic gastritis associated with H. pylori. METHODS: In a randomized clinical
      trial, patients were divided into two groups: a standard triple therapy group and
      triple therapy with curcumin group. Endoscopic and histological examinations were
      measured for all patients before and after 8 weeks. RESULTS: Triple therapy with
      curcumin treatment group significantly decreased malondialdehyde markers,
      glutathione peroxides and increased total antioxidant capacity of the gastric
      mucosa at the end of study compared to baseline and triple regimen groups. In
      addition, the oxidative damage to DNA was significantly decreased in triple
      therapy with curcumin group at the end of study compared to baseline and compared
      to triple therapy (P<0.05 for both). Triple therapy group in combination with
      Curcumin significantly decreased all active, chronic and endoscopic inflammation
      scores of patients compared to the baseline and triple therapy group (P<0.05 for
      both). The eradication rate by triple therapy + curcumin was significantly
      increased compared to triple therapy alone (P<0.05). CONCLUSION: Curcumin can be
      a useful supplement to improve chronic inflammation and prevention of
      carcinogenic changes in patients with chronic gastritis associated by H. pylori.

PMID- 28492712
TI  - LUGOL'S IODINE CHROMOENDOSCOPY VERSUS NARROW BAND IMAGE ENHANCED ENDOSCOPY FOR
      THE DETECTION OF ESOPHAGEAL CANCER IN PATIENTS WITH STENOSIS SECONDARY TO
      CAUSTIC/CORROSIVE AGENT INGESTION.
AB  - BACKGROUND: The diagnosis of corrosion cancer should be suspected in patients
      with corrosive ingestion if after a latent period of negligible symptoms there is
      development of dysphagia, or poor response to dilatation, or if respiratory
      symptoms develop in an otherwise stable patient of esophageal stenosis. Narrow
      Band Imaging detects superficial squamous cell carcinoma more frequently than
      white-light imaging, and has significantly higher sensitivity and accuracy
      compared with white-light. OBJECTIVE: To determinate the clinical applicability
      of Narrow Band Imaging versus Lugol's solution chromendoscopy for detection of
      early esophageal cancer in patients with caustic/corrosive agent stenosis.
      METHODS: Thirty-eight patients, aged between 28-84 were enrolled and examined by
      both Narrow Band Imaging and Lugol's solution chromendoscopy. A 4.9mm diameter
      endoscope was used facilitating examination of a stenotic area without dilation.
      Narrow Band Imaging was performed and any lesion detected was marked for later
      biopsy. Then, Lugol's solution chromoendoscopy was performed and biopsies were
      taken at suspicious areas. Patients who had abnormal findings at the routine,
      Narrow Band Imaging or Lugol's solution chromoscopy exam had their stenotic ring
      biopsied. RESULTS: We detected nine suspicious lesions with Narrow Band Imaging
      and 14 with Lugol's solution chromendoscopy. The sensitivity and specificity of
      the Narrow Band Imaging was 100% and 80.6%, and with Lugol's chromoscopy 100% and
      66.67%, respectively. Five (13%) suspicious lesions were detected both with
      Narrow Band Imaging and Lugol's chromoscopy, two (40%) of these lesions were
      confirmed carcinoma on histopathological examination. CONCLUSION: Narrow Band
      Imaging is an applicable option to detect and evaluate cancer in patients with
      caustic /corrosive stenosis compared to the Lugol's solution chromoscopy.

PMID- 28492713
TI  - FLAVONOIDS AND ANTI-OXIDANT ACTIVITY MEDIATED GASTROPROTECTIVE ACTION OF LEATHERY
      MURDAH, TERMINALIA CORIACEA (ROXB.) WIGHT & ARN. LEAF METHANOLIC EXTRACT IN RATS.
AB  - BACKGROUND: Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. from family
      Combretaceae is used in Ayurveda and Siddha traditional systems of medicine to
      heal ulcers. OBJECTIVE: The present study was conducted to assess the
      gastroprotective effect and understand the fundamental mechanism of action of
      Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. Leaf Methanolic
      Extract. METHODS: The test extract was screened for anti-ulcer activity by
      Aspirin induced ulcerogenesis in pyloric ligation and ethanol induced gastric
      ulcers at three doses - 125, 250, and 500 mg/kg, p.o. using Ranitidine 50 mg/kg
      and Misoprostol 100 MUg/kg as standard drug in respective models. Seven
      parameters were carefully examined, that is, ulcer index, total protein, mucin,
      catalase, malondialdehyde, and superoxide dismutase levels and histopathology.
      High Performance Liquid Chromatographic - Ultra Violet profiling and Liquid
      Chromatography - Mass Spectral analysis of crude Terminalia coriacea leaves
      methanolic extract were carried out as a part of chemical characterization to
      identify bioactive compounds. RESULTS: All the test doses exhibited significant
      gastroprotective function, particularly the higher doses demonstrated improved
      action. The results revealed a significant increase in the levels of catalase,
      superoxide dismutase, and Mucin with reduction in ulcer index, the levels of
      total protein, and malondialdehyde. Histopathological observations also
      illustrated the gastroprotective effect of Terminalia coriacea leaves methanolic
      extract. CONCLUSION: Terminalia coriacea leaves methanolic extract exhibited
      strong anti-oxidant and anti-secretory activities mediated gastroprotection
      besides inducing the gastric mucosal production. The observed pharmacological
      response can be attributed to the flavonoidal compounds namely - Quercetin-3-O
      rutinoside, Luteolin-7-O-glucoside, Myricetin hexoside, Quercetin-3-O-glucoside,
      Isorhamnetin-3-O-rhamnosylglucoside and Isorhamnetin-3-O-glucoside identified in
      the extract for the first time with High Performance Liquid Chromatographic -
      Ultra Violet and Liquid Chromatography - Mass Spectral analysis.

PMID- 28492714
TI  - MAST CELLS DISTINGUISH EOSINOPHILIC ESOPHAGITIS IN PEDIATRIC PATIENTS.
AB  - BACKGROUND: : Mast cells exert a substantial role in gastrointestinal allergic
      diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis
      in eosinophilic gastroenteropathy. OBJECTIVE: : To evaluate whether mast cell
      count in the esophageal epithelium can discriminate eosinophilic esophagitis,
      proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and
      gastroesophageal reflux esophagitis. METHODS:: Retrospectively we reviewed the
      files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with
      definitive diagnose established during clinical follow up in a universitary
      outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive
      eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15).
      Eosinophil count in the esophageal epithelium in slides stained with H-E was
      reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS::
      Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out
      of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar
      in eosinophilic esophagitis patients and in those with PPI-responsive
      eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47).
      Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median:
      25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis
      patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001.
      There was no difference between the mean count of mast cells/HPF in the
      esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive
      eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF,
      P=0.391. CONCLUSION: : Tryptase staining of mast cells differentiates
      eosinophilic esophagitis from reflux esophagitis.

PMID- 28492715
TI  - MANIPULATION OF THE INTESTINAL MICROBIOTA: THE MEDICINE REVOLUTION OF THE 21ST
      CENTURY.

PMID- 28492716
TI  - Prevalence of phonological disorders and phonological processes in typical and
      atypical phonological development.
AB  - Purpose: To determine the occurrence of phonological disorders by age, gender and
      school type, and analyze the phonological processes observed in typical and
      atypical phonological development across different age groups. Methods: The
      sample consisted of 866 children aged between 3:0 and 8:11 years, recruited from
      public and private schools in the city of Santa Maria/RS. A phonological
      evaluation was performed to analyze the operative phonological processes.
      Results: 15.26% (n = 132) of the sample presented atypical phonological
      acquisition (phonological disorders). Phonological impairments were more frequent
      in public school students across all age groups. Phonological alterations were
      most frequent between ages 4 -to 6, and more prevalent in males than females in
      all but the youngest age group. The most common phonological processes in typical
      phonological acquisition were: cluster reduction; nonlateral liquid deletion in
      coda; nonlateral liquid substitution in onset; semivocalization of lateral
      liquids in coda; and unstressed syllable deletion. In children with phonological
      disorders, the most common phonological processes were: lateral and nonlateral
      liquid substitution in onset position; nonlateral liquid deletion; fronting of
      fricatives in onset position; unstressed syllable deletion; semivocalization of
      nonlateral liquid in coda; and nonlateral liquid deletion in coda position.
      Conclusion: Phonological processes were highly prevalent in the present sample,
      and occurred more often in boys than in girls. Information regarding the type and
      frequency of phonological processes in both typical phonological acquisition and
      phonological disorders may contribute to early diagnosis and increase the
      efficiency of treatment planning.

PMID- 28492717
TI  - Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of
      Esophageal Leiomyoma.
AB  - OBJECTIVES:: Esophageal leiomyoma is the most common benign tumor of the
      esophagus, and it originates from mesenchymal tissue. This study analyzed the
      clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate
      the role of endoscopic ultrasonography in the diagnosis and treatment selection
      for these lesions. METHODS:: Two hundred and twenty-five patients who had
      suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at
      the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from
      January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic
      and morphological characteristics, symptoms, comparisons of diagnosis and
      treatment methods, adverse events, and prognosis. RESULTS:: One hundred and sixty
      seven patients were diagnosed as having an esophageal leiomyoma by pathological
      examination. The mean patient age was 50.57+/-9.983 years. In total, 62.9% of the
      lesions originated from the muscularis mucosa, and the others originated from the
      muscularis propria. The median distance to the incisors was 30+/-12 cm. The
      median diameter was 0.72+/-0.99 cm. As determined by endoscopic ultrasonography,
      most existing leiomyomas were homogeneous, endophytic, and spherical. The
      leiomyomas from the muscularis mucosa were smaller than those from the muscularis
      propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody)
      (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of
      treatments, patients preferred endoscopic therapies, which led to less adverse
      events (e.g., intraoperative bleeding, local infection, pleural effusion) than
      surgical operations (p<0.05). The superficial leiomyomas presented less adverse
      events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION:: Endoscopic
      ultrasonography has demonstrated high accuracy in the diagnosis of esophageal
      leiomyomas and provides great support in selecting treatments; however, EUS
      cannot completely avoid misdiagnosis, so combining it with other examinations may
      be a good strategy to solve this problem.

PMID- 28492718
TI  - Effects of Motor Learning on Clinical Isokinetic Test Performance in Knee
      Osteoarthritis Patients.
AB  - OBJECTIVES:: To analyze the effects of motor learning on knee extension-flexion
      isokinetic performance in knee osteoarthritis patients. METHODS:: One hundred and
      thirty-six middle-aged and older sedentary individuals (111 women, 64.3+/-9.9
      years) with knee osteoarthritis (130 patients with bilateral) and who had never
      performed isokinetic testing underwent two bilateral knee extension-flexion
      (concentric-concentric) isokinetic evaluations (5 repetitions) at 60 degrees
      /sec. The tests were first performed on the dominant leg with 2 min of recovery
      between test, and following a standardized warm-up that included 3 submaximal
      isokinetic repetitions. The same procedure was repeated on the non-dominant leg.
      The peak torque, peak torque adjusted for the body weight, total work,
      coefficient of variation and agonist/antagonist ratio were compared between
      tests. RESULTS:: Patients showed significant improvements in test 2 compared to
      test 1, including higher levels of peak torque, peak torque adjusted for body
      weight and total work, as well as lower coefficients of variation. The
      agonist/antagonist relationship did not significantly change between tests. No
      significant differences were found between the right and left legs for all
      variables. CONCLUSION:: The results suggest that performing two tests with a
      short recovery (2 min) between them could be used to reduce motor learning
      effects on clinical isokinetic testing of the knee joint in knee osteoarthritis
      patients.

PMID- 28492719
TI  - Does aortic valve repair in valve-sparing aortic root reconstruction compromise
      the longevity of the procedure?
AB  - OBJECTIVES:: The effect of performing aortic valve repair in combination with
      valve-sparing operation on the length of time for which patients are free from
      reoperation is unclear. The objective of this study was to determine if the
      performance of aortic valve repair during valve-sparing operation modified the
      freedom from reoperation time. METHODS:: From January 2003 to July 2014, 78
      patients with a mean age of 49+/-15 years underwent valve-sparing operation.
      Sixty-eight percent of these patients were male. Twenty-two (28%) aortic valve
      repair procedures were performed in this patient population. In the aortic valve
      repair + valve-sparing operation group, 77.3% of patients had moderate/severe
      aortic insufficiency, while in the valve-sparing operation group, 58.6% of
      patients had moderate/severe aortic insufficiency (ns = not significant).
      Additionally, 13.6% of patients in the aortic valve repair + valve-sparing
      operation group had functional class III/IV, while 14.2% of patients in the valve
      sparing operation group had functional class III/IV (ns). RESULTS:: The in
      hospital and late mortality rates, for the aortic valve repair + valve-sparing
      operation and valve-sparing operation groups were similar, as they were 4.5% and
      3.6%; and 0% and 1.8%, respectively. In the aortic valve repair + valve-sparing
      operation group, 0% of patients presented moderate/severe aortic insufficiency
      during late follow-up, while in the valve-sparing operation group, 14.2% of
      patients presented with moderate/severe aortic insufficiency during this period
      (ns). In the aortic valve repair + valve-sparing operation group, 5.3% of
      patients presented with functional class III/IV, while in the valve-sparing
      operation group, 4.2% of patients presented with functional class III/IV (ns). In
      the aortic valve repair + valve-sparing operation group, 0% of patients required
      reoperation, while in the valve-sparing operation group, 3.6% of patients
      required reoperation over a mean follow-up period of 1621+/-1156 days (75
      patients). CONCLUSION:: Valve-sparing operation is a safe and long-lasting
      procedure and performance of aortic valve repair when necessary does not increase
      risk of reoperation on the aortic valve.

PMID- 28492720
TI  - Association between language and hearing disorders - risk identification.
AB  - OBJECTIVE:: To identify children at risk for hearing and/or language disorders
      and to investigate the association between these risks by conducting pre
      validated hearing and language screenings. METHODS:: The study was conducted
      during a polio vaccination campaign in August of 2013 in basic health units in
      western Sao Paulo. Parents of children between 2 and 5 years of age were asked to
      complete two screening tools: a hearing questionnaire (regarding hearing
      development) and a language production and comprehension scale (including the
      major language development milestones). The screening tools were administered by
      different researchers. We compared the risk of having language disorders among
      children at risk for hearing loss versus children not at risk, as well as the
      attributable risk and odds ratios. Chi-squared tests and logistic regression
      analyses were used. RESULTS:: The study included 479 children with a mean age of
      three and one-half years, of whom 26.9% were identified as at risk for deficits
      in language production, 8.6% were at risk for deficits in language comprehension
      and 14% were at risk for hearing disorders. The children at risk for hearing
      disorders were twice as likely as those not at risk to exhibit language
      production and comprehension deficits. CONCLUSION:: The results of this study
      highlight the importance of establishing and adopting low-cost procedures such as
      screenings to identify children at risk of developing language and/or hearing
      disorders in early childhood.

PMID- 28492721
TI  - Treatment of acromegaly patients at the Federal University of Triangulo Mineiro
      (UFTM): Experience Report.
AB  - OBJECTIVE:: To evaluate the effectiveness of the treatment of acromegaly patients
      at the Federal University of Triangulo Mineiro. METHODS:: Cross-sectional and
      retrospective study of thirty cases treated over a period of two decades.
      RESULTS:: 17 men (56.7%) aged 14-67 years and 13 women aged 14-86 years were
      analyzed. Twenty-one patients underwent transphenoidal surgery, whichwas
      associated with somatostatin receptor ligands in 11 patients (39.3%),
      somatostatin receptor ligands + radiotherapyin 5 patients (17.8%), radiotherapy
      in 3 patients (10.7%), and radiotherapy + somatostatin receptorligands +
      cabergoline in 1 patient (3.6%). Additionally, 2 patients underwent radiotherapy
      and surgeryalone. Six patients received somatostatin receptor ligands before
      surgery, and 2 were not treated due to refusal and death. Nine patients have
      died, and 20 are being followed; 13 (65%) have growth hormonelevels o1 ng/mL, and
      11 have normal insulin-like growth factor 1 levels. CONCLUSION:: The current
      treatment options enable patients seen in regional reference centers to achieve
      strict control parameters, which allows them to be treated close to their homes.

PMID- 28492722
TI  - Insulin resistance and associated factors: a cross-sectional study of bank
      employees.
AB  - OBJECTIVE:: Insulin resistance is characterized by the failure of target cells to
      respond to normal levels of circulating insulin, and this condition is related to
      cardiovascular disease. This study sought to evaluate the prevalence of insulin
      resistance and its association with markers of metabolic abnormalities and
      metabolic syndrome in bank employees. METHODS:: A cross-sectional study was
      performed on 498 working men and women aged >=20 years old. The Homeostasis Model
      Assessment (HOMA-IR) was used to determine the presence of insulin resistance
      based on cut-off values of <=2.71 for normal insulin levels and >2.71 for insulin
      resistance, as established for the adult Brazilian population. RESULTS:: It was
      observed that the 52 (10.4%) overweight individuals with insulin resistance were
      4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the
      normal-weight participants; among those who were obese, the likelihood increased
      to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were
      3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than
      those who were within normal parameters. The HOMA-IR values differed between
      subjects with and without metabolic syndrome, with values of 2.83+/-2.5 and
      1.10+/-0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C
      reactive protein and uric acid were also associated with insulin resistance.
      CONCLUSION:: The prevalence of insulin resistance among bank employees is high,
      and insulin resistance is associated with and serves as a marker of metabolic
      syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic
      abnormalities were observed, and insulin resistance may be a risk factor in this
      group of professionals.

PMID- 28492723
TI  - Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and
      the Effects of Pamidronate Treatment.
AB  - OBJECTIVES:: The present study was designed to evaluate the bone phenotypes and
      mechanisms involved in bone disorders associated with hepatic osteodystrophy.
      Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition,
      the effects of disodium pamidronate on bone tissue were evaluated. METHODS:: The
      study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections;
      b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice
      subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4
      and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while
      pamidronate or vehicle was injected at the end of the fourth week. Bone
      histomorphometry and biomechanical analysis were performed in tibiae, while
      femora were used for micro-computed tomography and gene expression. RESULTS::
      CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular
      numbers, as well as increased trabecular separation, as determined by bone
      histomorphometry and micro-computed tomography, but these changes were not
      detected in the group treated with pamidronate. CCl4 mice showed increased
      numbers of osteoclasts and resorption surface. High serum levels of receptor
      activator of nuclear factor-kappaB ligand and the increased expression of
      tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the
      enhancement of bone resorption in these mice. CONCLUSION:: Taken together, these
      results suggest that bone resorption is the main mechanism of bone loss in
      chronic hepatocellular disease in mice.

PMID- 28492724
TI  - Human islet xenotransplantation in rodents: A literature review of experimental
      model trends.
AB  - Among the innovations for the treatment of type 1 diabetes, islet transplantation
      is a less invasive method of treatment, although it is still in development. One
      of the greatest barriers to this technique is the low number of pancreas donors
      and the low number of pancreases that are available for transplantation. Rodent
      models have been chosen in most studies of islet rejection and type 1 diabetes
      prevention to evaluate the quality and function of isolated human islets and to
      identify alternative solutions to the problem of islet scarcity. The purpose of
      this study is to conduct a review of islet xenotransplantation experiments from
      humans to rodents, to organize and analyze the parameters of these experiments,
      to describe trends in experimental modeling and to assess the viability of this
      procedure. In this study, we reviewed recently published research regarding islet
      xenotransplantation from humans to rodents, and we summarized the findings and
      organized the relevant data. The included studies were recent reports that
      involved xenotransplantation using human islets in a rodent model. We excluded
      the studies that related to isotransplantation, autotransplantation and
      allotransplantation. A total of 34 studies that related to xenotransplantation
      were selected for review based on their relevance and current data. Advances in
      the use of different graft sites may overcome autoimmunity and rejection after
      transplantation, which may solve the problem of the scarcity of islet donors in
      patients with type 1 diabetes.

PMID- 28492726
TI  - Theoretical basis, application, reliability, and sample size estimates of a
      Meridian Energy Analysis Device for Traditional Chinese Medicine Research.
AB  - OBJECTIVES:: The Meridian Energy Analysis Device is currently a popular tool in
      the scientific research of meridian electrophysiology. In this field, it is
      generally believed that measuring the electrical conductivity of meridians
      provides information about the balance of bioenergy or Qi-blood in the body.
      METHODS AND RESULTS:: PubMed database based on some original articles from 1956
      to 2014 and the authors clinical experience. In this short communication, we
      provide clinical examples of Meridian Energy Analysis Device application,
      especially in the field of traditional Chinese medicine, discuss the reliability
      of the measurements, and put the values obtained into context by considering
      items of considerable variability and by estimating sample size. CONCLUSION:: The
      Meridian Energy Analysis Device is making a valuable contribution to the
      diagnosis of Qi-blood dysfunction. It can be assessed from short-term and long
      term meridian bioenergy recordings. It is one of the few methods that allow
      outpatient traditional Chinese medicine diagnosis, monitoring the progress,
      therapeutic effect and evaluation of patient prognosis. The holistic approaches
      underlying the practice of traditional Chinese medicine and new trends in modern
      medicine toward the use of objective instruments require in-depth knowledge of
      the mechanisms of meridian energy, and the Meridian Energy Analysis Device can
      feasibly be used for understanding and interpreting traditional Chinese medicine
      theory, especially in view of its expansion in Western countries.

PMID- 28492725
TI  - Breast cancer screening in developing countries.
AB  - Developing countries have limited healthcare resources and use different
      strategies to diagnose breast cancer. Most of the population depends on the
      public healthcare system, which affects the diagnosis of the tumor. Thus, the
      indicators observed in developed countries cannot be directly compared with those
      observed in developing countries because the healthcare infrastructures in
      developing countries are deficient. The aim of this study was to evaluate breast
      cancer screening strategies and indicators in developing countries. A systematic
      review and the Population, Intervention, Comparison, Outcomes, Timing, and
      Setting methodology were performed to identify possible indicators of
      presentation at diagnosis and the methodologies used in developing countries. We
      searched PubMed for the terms "Breast Cancer" or "Breast Cancer Screening" and
      "Developing Country" or "Developing Countries". In all, 1,149 articles were
      identified. Of these articles, 45 full articles were selected, which allowed us
      to identify indicators related to epidemiology, diagnostic intervention
      (diagnostic strategy, diagnostic infrastructure, percentage of women undergoing
      mammography), quality of intervention (presentation of symptoms at diagnosis,
      time to diagnosis, early stage disease), comparisons (trend curves,
      subpopulations at risk) and survival among different countries. The
      identification of these indicators will improve the reporting of methodologies
      used in developing countries and will allow us to evaluate improvements in public
      health related to breast cancer.

PMID- 28492727
TI  - Active caspase-3 expression levels as bioindicator of individual
      radiosensitivity.
AB  - Several molecules and events involved in cell response to radiation-induced
      damage have been investigated towards a personalized radiotherapy. Considering
      the importance of active caspase-3 in the proteolytic cascade that ensures
      radiation-induced apoptosis execution, this research was designed to evaluate the
      expression levels of this protein as a bioindicator of individual
      radiosensitivity. Peripheral blood samples of 10 healthy individuals were gamma
      irradiated (cobalt-60 source) with 1, 2 and 4 Gy (control: non-irradiated
      samples), and active caspase-3 expression levels were measured in lymphocytes, by
      flow cytometry, ex vivo and after different times of in vitro incubation (24, 48
      and 72 hours). Short-term incubation of 24 h was the most adequate condition to
      evidence correlations between dose radiation and active caspase-3 expression. For
      each radiation dose, it was observed a significant inter-individual variation in
      active caspase-3 expression intensity, suggesting that this parameter may be
      suitable for evidence individual radiosensitivity. The methodology presented and
      discussed in this work may help to predict healthy tissues response to radiation
      exposure toward the better patient outcome.

PMID- 28492728
TI  - Evaluation of the predisposition and clinical impact of BK virus replication in
      kidney transplant patients.
AB  - The BK virus (BKV) produces a subclinical kidney infection in immunocompetent
      individuals. However, viremia may occur in kidney transplant patients with
      ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific
      treatment and is a leading cause of organ transplant loss. In this study, we
      evaluated the predisposition and the clinical impact of BKV replication in kidney
      transplant patients during post-transplant monitoring in a reference institution
      in Brazil. Demographic, clinical and laboratory data generated during routine
      outpatient follow-up were retrospectively collected. BK viremia was investigated
      using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41)
      presented BKV replication. Of these, 16 (39%) lost their kidney graft and
      interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among
      the evaluated variables, only the use of the immunosuppressant mycophenolate
      sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to
      26.98). The graft survival estimate in BKV-positive patients was significantly
      reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that
      defining predisposing factors remains an important challenge for the prevention
      and control of BKV activity following kidney transplantation, especially
      considering the development of BKVN and its strong effect on graft maintenance.

PMID- 28492729
TI  - CYP2B6 516 G>T polymorphism and side effects of the central nervous system in HIV
      positive individuals under Efavirenz treatment: Study of a sample from southern
      Brazil.
AB  - This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and
      evaluate its influence on central nervous system (CNS) side effect development in
      HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population
      from southern Brazil. Additionally, we performed a survey on the clinical and
      epidemiological characteristics of our sample. In addition to medical records
      evaluation, whole blood of 89 individuals was analyzed for viral load, T
      lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side
      effects of the CNS reported by individuals but without considering the genetic
      variables, no statistically significant association was noted between the adverse
      effects and the antiretroviral treatment (including or not EFV). In addition, no
      statistically significant difference was noted for the influence of genotype on
      the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals
      undergoing EFV treatment. This is the first study that investigated the impact of
      the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from
      southern Brazil. Its clinical significance indicates the need for prospective
      studies in this population.

PMID- 28492730
TI  - Paleoenvironmental Evolution of Continental Carbonates in West-Central Brazil.
AB  - This paper presents a sedimentological and stratigraphical study of Quaternary
      (Middle to Late Pleistocene/Holocene) continental carbonates outcrops inside
      Pantanal Basin and its surroundings, especially in Serra da Bodoquena, Pantanal
      do Miranda and Corumba/Ladario plateau, in the state of Mato Grosso do Sul, as
      well as in Serra das Araras, in the state of Mato Grosso. The aim is to
      understand the depositional paleoenvironments and analyse climate and tectonic
      influences in their genesis and evolution. The results show that the deposition
      of these continental carbonates started in the Middle to Late Pleistocene and
      have continued, with some interruptions, until the present days. Sedimentary
      successions were identified in the different areas, without complete correlation.
      Two sedimentary successions separated by an erosional surface were described in
      Serra da Bodoquena and Serra das Araras. In Corumba and Pantanal do Miranda, only
      one succession was described. These successions were deposited in elongated lakes
      parallel to fault planes; small lakes, related plains and plateaus; springs
      related to cliffs produced by faulting; rivers conditioned by topographic
      variation. The climatic interpretation, without proper temporal resolution,
      obtained by the stable-isotope composition and stratigraphic interpretation,
      indicates alternation of dry and wet periods. The Neoproterozoic faults with
      their neotectonics and the subsidence of the Pantanal Basin, are the major
      control for carbonated water flow and development of depositional areas,
      gradually turning plateaus into slight tilted areas, allowing the evolution of
      depositional systems from lakes to rivers.

PMID- 28492731
TI  - Brazilian Scientific Mobility Program - Science without Borders - Preliminary
      Results and Perspectives.
AB  - The Brazilian Scientific Mobility Program - Science without Borders (SwB) - saw
      the concession of over 101 thousand scholarships for Brazilian STEM students and
      education professionals to attend universities worldwide. As the first phase of
      this program ends, it is time to take a first look at its impacts, mainly on the
      undergraduate student body (79% of total scholarships implemented). Benefits
      included a 6-month language course (optional), a one year undergraduate course
      and optional 2 month internship in a university, government laboratory or
      technology company. Positive impacts have been seen on entrance into post
      graduate programs (>20% of SwB students compared to <5% of the overall student
      body of similar fields), as well as high representation of lower income families
      (>50% from families with less than 6 minimum wages per month). The impact of the
      program will need to be evaluated over the next years, but innovation on the part
      of the students is already apparent. Any new SwB program needs to take into
      account the lessons learned from this first experience and therefore
      recommendations are presented.

PMID- 28492732
TI  - Going Beyond Academic Integrity Might Broaden our Understanding of Plagiarism in
      Science Education: A Perspective from a Study in Brazil.
AB  - Fostering innovation and creativity is a priority in the science and education
      policy agenda of most countries, which have advocated that innovative minds and
      processes will boost scientific and economic growth. While our knowledge society
      has embraced this view, fostering creativity is among the major challenges faced
      by educators and policymakers. For example, plagiarism, which may be considered a
      form of imitation and repetition, is a global concern at schools and
      universities. However, most discussions focus on academic integrity, which, we
      believe, leaves some gaps in the approach to the problem. As part of an ongoing
      project on plagiarism, science and education policy, we show results from a
      survey sent to 143 high-school science teachers at one of the most highly
      regarded federal schools in Brazil. Among respondents (n=42), about 50% admit
      that students plagiarize in assignments. Additionally, many of these educators
      suggest that the way biology, chemistry and physics are taught at school
      stimulates more repetition than creativity. Our findings are consistent with the
      need for a broader perspective on plagiarism and with initiatives to stimulate
      creativity and critical thinking among students. Although we offer a perspective
      from Brazil, it may illuminate current discussions on plagiarism, particularly in
      emerging countries.

PMID- 28492733
TI  - Simultaneous Determination of Furan and Vinyl Acetate in Vapor Phase of
      Mainstream Cigarette Smoke by GC-MS.
AB  - A simple and sensitive method for simultaneous determination of furan and vinyl
      acetate (VA) in vapor phase of mainstream cigarette smoke with cold trap and gas
      chromatography-mass spectrometry (GC-MS) was developed. A Cambridge filter pad
      (CFP) was placed in front of the impingers of smoking machine to remove the
      particle phase from cigarette smoke. Furan and VA in vapor phase of mainstream
      cigarette smoke were collected in two impingers connected in series by filled
      with methanol at -78 degrees C. The solutions were added with deuterium-labeled
      furan-d4 and VA-d6 as internal standards and analyzed by GC-MS. The results
      showed that the calibration curves for furan and VA were linear (r2 > 0.9995)
      over the studied concentration range. The intra- and inter-day precision values
      for furan and VA were <7.07% and <9.62%, respectively. The extraction recoveries
      of furan and VA were in the range of 94.5-97.7% and 92.3-94.9%, respectively.
      Moreover, the limits of detection for furan and VA were 0.028 ug mL-1 and 1.3 ng
      mL-1, respectively. The validated method has been successfully applied to
      determine the emissions of furan and VA in the vapor phase of mainstream
      cigarette smoke under International Organization for Standardization (ISO) and
      Canadian Intense (CI) smoking regimen.

PMID- 28492734
TI  - Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya:
      an approach on blood parameters.
AB  - This study investigated the anesthetic potential of the essential oil (EO) of
      Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish
      were exposed to different concentrations of EO of A. polystachya to evaluate time
      of induction and recovery from anesthesia. In the second experiment, fish were
      divided into four groups: control, ethanol and 50 or 300 uL L-1 EO of A.
      polystachya, and each group was submitted to induction for 3.5 min and recovery
      for 5 or 10 min. The blood gases and glucose levels showed alterations as a
      function of the recovery times, but Na+ and K+ levels did not show any
      alteration. In conclusion, the EO from leaves of A. polystachya is an effective
      anesthetic for dusky grouper, because anesthesia was reached within the
      recommended time at EO concentrations of 300 and 400 uL L-1. However, most
      evaluated blood parameters showed compensatory responses due to EO exposure.

PMID- 28492735
TI  - Subclinical Diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide, and those
      non-diagnosed or misdiagnosed comprise a significant group compared to those
      diagnosed. Accumulated scientific evidence indicate that the current diagnostic
      markers (fasting glycemia, 2h glycemia after an oral glucose load and HbA1c) are
      indeed late diagnostic criteria when considering the incidence of diabetes
      related complications and comorbidities, which are also at high risk in some
      groups among normoglycemic individuals. Additionally, the earlier identification
      of future risk of diabetes is desirable since it would allow better adherence to
      preventive actions such as lifestyle intervention, ultimately avoiding
      complications and minimizing the economic impact/burden on health care expenses.
      Insulin resistance and hyperhormonemia (insulin, amylin, glucagon) are non
      disputable hallmarks of T2DM, which already takes place among these
      normoglycemic, otherwise health subjects, characterizing a state of subclinical
      diabetes. Insulin resistance and hyperinsulinemia can be computed from fasting
      plasma insulin as an independent variable in normoglycemia. An overview of the
      current diagnostic criteria, disease onset, complications, comorbidities and
      perspectives on lifestyle interventions are presented. A proposal for early
      detection of subclinical diabetes from routine evaluation of fasting plasma
      insulin, which is affordable and robust and thus applicable for the general
      population, is further suggested.

PMID- 28492736
TI  - Effect of drying method on mechanical, thermal and water absorption properties of
      enzymatically crosslinked gelatin hydrogels.
AB  - Enzymatically crossliked gelatin hydrogel was submitted to two different drying
      methods: air drying and freeze drying. The resulting polymeric tridimensional
      arrangement (compact or porous, respectively) led to different thermal and
      swelling properties. Significant differences (p < 0.05) on thermal and mechanical
      characteristics as well as swelling in non-enzymatic gastric and intestinal
      simulated fluids (37 oC) were detected. Water absorption data in such media was
      modelled according to Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin equations.
      Freeze dried hydrogel showed Fickian diffusion behavior while air dried hydrogels
      presented poor adjustment to Higuchi model suggesting the importance of the
      relaxation mechanism at the beginning of swelling process. It was possible to
      conclude that the same gelatin hydrogel may be suitable to different applications
      depending on the drying process used.

PMID- 28492737
TI  - The use of medicinal plants and the role of faith in family care.
AB  - Objective: To understand the use of medicinal plants and the role of faith in the
      family care system. Method: The adopted methodology is qualitative research,
      conducted in April and July 2015, in a municipality of Rio Grande do Sul, Brazil,
      Brazil, with three informants who have knowledge of the healthcare practices. The
      data were interpreted using interpretive anthropology. Results: Data
      interpretation led to two categories: Medicinal plants in health care and Care
      with the use of plants in the blessing ritual. It was identified that the use of
      plants and faith healing is a particular form of self-care in that given
      community. The purpose of this practice is to cure people from a biological and
      comprehensive perspective, involving the body, soul, spirit, and environment.
      Conclusion: The research revealed that medicinal plants go beyond the merely
      biological relationship in the family care system. Use of these plants is not
      based on the principle of buying and selling, but rather on the act of
      exchanging, giving, receiving, and reciprocating.

PMID- 28492739
TI  - Relationship between Resting Heart Rate, Blood Pressure and Pulse Pressure in
      Adolescents.
AB  - Background:: High resting heart rate is considered an important factor for
      increasing mortality chance in adults. However, it remains unclear whether the
      observed associations would remain after adjustment for confounders in
      adolescents. Objectives:: To analyze the relationship between resting heart rate,
      blood pressure and pulse pressure in adolescents of both sexes. Methods:: A cross
      sectional study with 1231 adolescents (716 girls and 515 boys) aged 14-17 years.
      Heart rate, blood pressure and pulse pressure were evaluated using an
      oscillometric blood pressure device, validated for this population. Weight and
      height were measured with an electronic scale and a stadiometer, respectively,
      and waist circumference with a non-elastic tape. Multivariate analysis using
      linear regression investigated the relationship between resting heart rate and
      blood pressure and pulse pressure in boys and girls, controlling for general and
      abdominal obesity. Results:: Higher resting heart rate values were observed in
      girls (80.1 +/- 11.0 beats/min) compared to boys (75.9 +/- 12.7 beats/min) (p <=
      0.001). Resting heart rate was associated with systolic blood pressure in boys
      (Beta = 0.15 [0.04; 0.26]) and girls (Beta = 0.24 [0.16; 0.33]), with diastolic
      blood pressure in boys (Beta = 0.50 [0.37; 0.64]) and girls (Beta = 0.41 [0.30;
      0.53]), and with pulse pressure in boys (Beta = -0.16 [-0.27; -0.04]).
      Conclusions:: This study demonstrated a relationship between elevated resting
      heart rate and increased systolic and diastolic blood pressure in both sexes and
      pulse pressure in boys even after controlling for potential confounders, such as
      general and abdominal obesity. Fundamento:: A frequencia cardiaca de repouso e
      considerada um importante fator de aumento de mortalidade em adultos. Entretanto,
      ainda e incerto se as associacoes observadas permanecem apos ajuste para fatores
      de confusao em adolescentes. Objetivos:: Analisar a relacao entre frequencia
      cardiaca de repouso, pressao arterial e pressao de pulso em adolescentes dos dois
      sexos. Metodos:: Estudo transversal com 1231 adolescentes (716 meninas e 515
      meninos, idade de 14-17 anos). Frequencia cardiaca, pressao arterial e pressao de
      pulso foram avaliadas com esfigmomanometro oscilometrico validado para essa
      populacao. Peso e altura foram medidos com balanca eletronica e estadiometro,
      respectivamente, e a circunferencia abdominal, com uma fita inextensivel. Analise
      multivariada com regressao linear investigou a relacao entre frequencia cardiaca
      de repouso, pressao arterial e pressao de pulso em meninos e meninas, controlando
      para obesidade geral e abdominal. Resultados:: Valores maiores de frequencia
      cardiaca de repouso foram observados em meninas (80,1 +/- 11,0 bpm) em comparacao
      a meninos (75,9 +/- 12,7 bpm) (p <= 0,001). Frequencia cardiaca de repouso
      associou-se com pressao arterial sistolica em meninos [Beta = 0,15 (0,04; 0,26)]
      e meninas [Beta = 0,24 (0,16; 0,33)], com pressao arterial diastolica em meninos
      [Beta = 0,50 (0,37; 0,64)] e meninas [Beta = 0,41 (0,30; 0,53)], e com pressao de
      pulso apenas em meninos [Beta = -0,16 (-0,27; -0,04)]. Conclusoes:: Este estudo
      demonstrou a relacao da frequencia cardiaca de repouso elevada com aumento das
      pressoes arteriais sistolica e diastolica em ambos os sexos e com pressao de
      pulso em meninos, mesmo apos controle para potenciais fatores de confusao, como
      obesidade geral e abdominal.

PMID- 28492738
TI  - Factors Associated With Coronary Artery Disease Progression Assessed By Serial
      Coronary Computed Tomography Angiography.
AB  - Background: Coronary computed tomography angiography (CCTA) allows for
      noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD
      progression are epidemiologically valuable. Objective: To identify factors
      associated with CAD progression in patients undergoing sequential CCTA testing.
      Methods: We retrospectively analyzed 384 consecutive patients who had at least
      two CCTA studies between December 2005 and March 2013. Due to limitations in the
      quantification of CAD progression, we excluded patients who had undergone
      surgical revascularization previously or percutaneous coronary intervention (PCI)
      between studies. CAD progression was defined as any increase in the adapted
      segment stenosis score (calculated using the number of diseased segments and
      stenosis severity) in all coronary segments without stent (in-stent restenosis
      was excluded from the analysis). Stepwise logistic regression was used to assess
      variables associated with CAD progression. Results: From a final population of
      234 patients, a total of 117 (50%) had CAD progression. In a model accounting for
      major CAD risk factors and other baseline characteristics, only age (odds ratio
      [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR
      1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an
      independent relationship with CAD progression. Conclusions: A history of PCI with
      stent placement was independently associated with a 3.7-fold increase in the odds
      of CAD progression, excluding in-stent restenosis. Age and interstudy interval
      were also independent predictors of progression.

PMID- 28492740
TI  - Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A
      Histomorphometric Study in Rats.
AB  - The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone
      quantity and quality were investigated for years. However, there is lack of
      information on the impact of NSAIDs on the quality of tooth-supporting alveolar
      bone in absence of periodontal inflammation. Thus, the aim of this study was to
      evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on
      the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar
      rats were randomly divided into four experimental groups: Subcutaneous injection
      of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and
      subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4;
      n=13). Mineral density was histometrically determined in the inter-radicular area
      of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%).
      Results showed no interaction between time and treatment (p>0.05) and that
      meloxicam did not affect the alveolar bone density. In contrast, it was found
      that inter-radicular alveolar bone density increased with time (91.88+/-3.08% and
      92.86+/-2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the
      limits of this study, daily administration of a selective COX-2 inhibitor
      (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in
      absence of periodontal infection.

PMID- 28492741
TI  - Effect of Alox-15 Polymorphism on GCF Levels of Lipoxin-A4 in Chronic
      Periodontitis: A Preliminary Study.
AB  - Lipoxins play an important role in periodontal resolution, hence, investigation
      of genetic polymorphism of lipoxin gene may provide important information on the
      role of lipoxins in periodontal disease pathogenesis. The aim of this study was
      to investigate a polymorphism of C-to-T substitution at position c.-292 in ALOX15
      (reticulocyte-type 15 lipoxygenase 1) gene in patients with chronic periodontitis
      and to associate the polymorphism with gingival crevicular fluid (GCF) lipoxin A4
      (LXA4) levels. Forty-five chronic periodontitis and 45 periodontally healthy
      patients were included in this case-control study. Plaque index, calculus index,
      sulcus bleeding index, full mouth probing depth (PD) and clinical attachment loss
      (CAL) were recorded. GCF and blood samples were collected. GCF was analyzed for
      LXA4 levels by enzyme linked immunosorbant assay. Genotyping of ALOX15
      polymorphism was studied using PCR. Mean LXA4 was lower in periodontitis group
      compared to the periodontally healthy group. There was a negative correlation
      between CAL and LXA4. The CC genotype was higher in the study group than in the
      control group. In the study group, mean CAL was significantly lower among
      individuals with the CT genotype. Mean LXA4 was significantly lower in CC
      genotype (45.0+/-7.11 ng/mL) compared to CT genotype (50.81+/-5.81 ng/mL) among
      the patients with periodontitis. The results suggest that LXA4 and c.-292T allele
      are associated with periodontal health. Polymorphisms in the ALOX15 gene may
      influence periodontal disease pathogenesis. Hence, investigation of such
      polymorphisms could benefit the evaluation of lipoxins role in periodontal
      disease.

PMID- 28492742
TI  - DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44
      Protein Expression.
AB  - Chromosomal instability, leading to aneuploidy, is one of the hallmarks of human
      cancers. USP44 (ubiquitin specific peptidase 44) is an important molecule that
      plays a regulatory role in the mitotic checkpoint and USP44 loss causes
      chromosome mis-segregation, aneuploidy and tumorigenesis in vivo. In this study,
      it was investigated the immunoexpression of USP44 in 28 malignant salivary gland
      neoplasms and associated the results with DNA ploidy status assessed by image
      cytometry. USP44 protein was widely expressed in most of the tumor samples and no
      clear association could be established between its expression and DNA ploidy
      status or tumor size. On this basis, it may be concluded that the aneuploidy of
      the salivary gland cancers included in this study was not driven by loss of USP44
      protein expression.

PMID- 28492743
TI  - Presence of Cells in Fresh-Frozen Allogeneic Bone Grafts from Different Tissue
      Banks.
AB  - Bone replacement materials have been widely used to reconstruct atrophic
      jawbones. Based on previous reports demonstrating the presence of viable cells in
      bone blocks even after processing by musculoskeletal tissue banks for orthopedic
      use, the aim of this study was to evaluate the presence of cells in bone blocks
      from three Brazilian tissue banks for maxillary reconstructions. All samples were
      processed by the respective tissue banks, according to the guidelines of the
      Brazilian National Sanitary Surveillance Agency. Three samples were removed from
      each block for subsequent histological processing and stained using hematoxylin &
      eosin. Further evaluation included section staining by the Feulgen method and
      ultrastructural analysis using scanning electron microscopy (SEM). Light
      microscopy images from all bone samples showed presence of osteocyte-like cells
      in all groups and intense Feulgen staining, demonstrating presence of DNA in bone
      even after tissue processing. The ultrastructural analysis showed red blood cells
      in lacunae within the bone tissue. In conclusion, despite bone tissue processing
      by the musculoskeletal tissue banks, cells may be found within the bone used for
      allogeneic grafts.

PMID- 28492744
TI  - Surface Properties of Temporary Soft Liners Modified by Minimum Inhibitory
      Concentrations of Antifungals.
AB  - Evaluating the addition of minimum inhibitory concentrations (MICs) of
      antifungals for Candida albicans biofilm on the hardness and roughness of
      temporary denture soft liners. Specimens (n=8; 36*7*6 mm) of tissue conditioner
      (Softone) and resilient liner (Trusoft) were produced either without (control) or
      with incorporation of drugs at MICs: nystatin (0.032 g/mL), chlorhexidine
      diacetate (0.064 g/mL), ketoconazole (0.128 g/mL), miconazole (0.256 g/mL) and
      itraconazole (0.256 g/mL). Specimens were stored in distilled water at 37 
      degrees C for 24 h, 7 days and 14 days prior to the hardness/roughness
      measurements. Data were analyzed by 3-way ANOVA and Tukey HSD test (alpha=0.05).
      The addition of the antifungals into both materials demonstrated no evident
      hardness change or decrease of this property compared with the control, except
      for miconazole in Softone, which increased the hardness after 14 days (p=0.003).
      The addition of nystatin into both materials, chlorhexidine in Trusoft and
      ketoconazole in Softone resulted in no significant changes of roughness compared
      with the control, after 7 days and 14 days (p>0.05). In these periods,
      itraconazole increased the roughness of both materials (p<0.001). The addition of
      all antifungals, except for the miconazole in Softone, resulted in no deleterious
      effects on the materials' hardness over the evaluation time. The MICs of nystatin
      in both temporary soft lining materials, ketoconazole in Softone and
      chlorhexidine in Trusoft resulted in no deleterious effects for roughness up to
      14 days.

PMID- 28492745
TI  - Cytotoxicity Evaluation of Root Canal Sealers Using an In Vitro Experimental
      Model with Roots.
AB  - The aim of the present study was to evaluate the cytotoxicity of root canal
      sealers under conditions closely resembling a clinical reality. A primary human
      fibroblast cell line was seeded in 24-well acrylic plates with Dulbecco's
      modified Eagle's medium supplemented with 10% serum fetal bovine (SFB) and
      incubated for 24 h. Root canals from premolars were filled and individually
      attached to nylon devices to be stabilized in the wells with the already seeded
      cells. Specimens were divided into groups as follows: Control: gutta-percha cones
      (GPC); AH Plus+GPC; Sealapex+GPC; MTA Fillapex+GPC and Endofill+GPC. After 24 and
      48 h, cell viability and morphology were evaluated by MTT assay and scanning
      electron microscopy (SEM), respectively. Statistical analysis was performed by
      Mann-Whitney test, complemented by Kruskal Wallis test (p<0.05). Only Endofill
      presented cytotoxicity after 24 h. MTA Fillapex and Endofill reduced the
      production of succinic desidrogenase after 48 h. AH Plus was non-toxic at any
      time point. SEM showed that the AH Plus and MTA Fillapex groups presented
      fibroblasts with morphology close to the control group, while the Endofill group
      presented few cells with thin extensions cells. The present study showed that
      good results were present in AH Plus and Sealapex, but not the Endofill group
      after 48 h. The method used enabled evaluation of the cytotoxicity of the studied
      sealers that diffused through the root apex.

PMID- 28492746
TI  - ?
AB  - Developing new restorative materials should avoid damage to tissue structures.
      This study evaluated the biocompatibility of a commercial dental glass ionomer
      cement (GIC) mechanically reinforced with cellulose microfibers (GIC+CM) or
      cellulose nanocrystals (GIC+CN) by implantation of three test specimens in
      subcutaneous tissue in the dorsal region of 15 Rattus norvegicus albinus rats.
      Each rat received one specimen of each cement, resulting in the following groups
      (n=15): Group GIC (Control), Group GIC+CM and Group GIC+NC. After time intervals
      of 7, 30 and 60 days, the animals were sacrificed and the following aspects were
      histologically evaluated: type of inflammatory cells, fibroblasts, blood vessels,
      macrophages, giant cells, type of inflammatory reaction and capsule thickness
      (um). These events were scored as (-) absent, (+) light, (++) moderate and (+++)
      intense. The results were statistically analyzed by Kruskal-Wallis test and Mann
      Whitney post test. At 7 days, Group GIC+NC showed more favorable tissue repair
      because quantitatively there were more fibroblasts (p=0.022), fewer macrophages
      (p=0.008) and mononuclear cells (p=0.033). Polymorphonuclear neutrophils and
      giant cells were absent in all experimental periods. At 60 days, test specimens
      in Group GIC+NC were surrounded by a fibrous tissue capsule with reduced
      thickness (26.72+/-2.87 um) in comparison with Group GIC+CM (41.21+/-3.98 um)
      (p=0.025). In general, all biomaterials showed satisfactory biocompatibility, but
      glass ionomer cement modified with cellulose nanocrystals showed a more advanced
      tissue repair.

PMID- 28492747
TI  - Common Operative Procedural Errors and Clinical Factors Associated with Root
      Canal Treatment.
AB  - Operative procedural errors must be well analyzed in order to avoid influence
      negatively the root canal treatment (RCT) prognosis. The successful RCT prevents
      tooth loss and avoids pain and apical periodontitis. This review aimed to
      categorize common operative procedure errors and clinical factors associated with
      RCT. Based on this, will be approached common errors of procedures within the
      clinical operative sequence: endodontic treatment planning, pulp and periapical
      disease diagnosis, anaesthesia, access cavity preparation, isolation with rubber
      dam, root canal preparation, root canal filling and retreatment, restoration of
      endodontically treated teeth, postoperative pain, follow up of endodontically
      treated teeth. The professional must remind that in each phase of RCT an
      operative error may have adverse implication on prognosis, and these errors
      characterize risk factors to failure. The knowledge of probable operative
      procedural errors and its consequences are essentials to avoid future problems to
      the tooth health.

PMID- 28492748
TI  - Influence of Resin Cements on Color Stability of Different Ceramic Systems.
AB  - The purpose of this study was to evaluate color stability of two dental ceramics
      cemented with two resin cements, assessing the color difference (DeltaE00) by the
      measurement of L*, a*, b*, c* and h* of transmittance. The combination of two
      ceramic system (feldspathic and lithium disilicate) and two resin cements - color
      A3 (RelyX ARC and Variolink II) resulted in 4 groups (n=5). Ten disks-shaped
      specimens were fabricated for each ceramic system (10x1.5 mm), etched with
      hydrofluoric acid (10%) and silanized prior to cementation. The color analysis
      was performed 24 h after cementation of the samples and after 6 months of storage
      in relative humidity by means of spectrophotometry. The DeltaE00 values were
      analyzed statistically by two-way ANOVA followed by the Tukey test (p<0.05). One
      way ANOVA were calculated for the means of individual color coordinates (L*, a*,
      b*, c* and h*). Two-way ANOVA showed that only the ceramic factor was significant
      (p=0.003), but there was no difference for the cement factor (p=0.275) nor for
      the ceramic/cement interaction (p=0.161). The feldspathic ceramic showed the
      highest values of DeltaE00. Variations in L*, a*, b*, c* and h* were more
      significant for feldspathic ceramic. In conclusion, storage alters similarly the
      optical properties of the resin cements and feldspathic porcelain was more
      susceptible to cement color change after aging.

PMID- 28492749
TI  - Triazine Compound as Copolymerized Antibacterial Agent in Adhesive Resins.
AB  - The aim of this study was to formulate and evaluate an experimental adhesive
      resin with the addition of 1,3,5-triacryloylhexahydro-1,3,5-triazine at different
      concentrations. Experimental adhesive resins were obtained by mixing 50% wt
      bisphenol A glycol dimethacrylate (BisGMA), 25% wt triethylene glycol
      dimethacrylate (TEGDMA), 25% wt 2-hydroxyethyl methacrylate (HEMA) and
      photoinitiator system. The triazine compound was added in 1, 2.5 and 5% wt to a
      base adhesive resin and one group remained with no triazine as control group. The
      experimental adhesive resins were analyzed for antibacterial activity (n=3),
      degree of conversion (n=3) and softening in solvent (n=3). Data distribution was
      evaluated by Kolmogorov-Smirnov test, paired t test, one-way ANOVA and Tukey's
      with a 0.05 level of significance. All groups with added triazine compound showed
      antibacterial activity against Streptococcus mutans (p<0.05). All groups achieved
      more than 70% degree of conversion, but there was no difference in this chemical
      property (p>0.05). The initial Knoop hardness was higher in 2.5 and 5% wt groups
      (p<0.05) and both groups present lower percentage variation of Knoop hardness
      after solvent degradation. The present study formulated an antibacterial adhesive
      resin with a non-releasing agent able to copolymerize with the comonomeric blend,
      improving the restorative material's properties.

PMID- 28492750
TI  - Relationship between Initial Attendance after Dental Trauma and Development of
      External Inflammatory Root Resorption.
AB  - This clinical study aimed to evaluate the relationship of the delay between
      dental trauma and the initial attendance to the development of external
      inflammatory root resorption in permanent teeth affected by severe luxation.
      Sixty-seven patients, aged between 11 and 56 years, presenting 133 injured teeth
      with closed apex (56 extrusive luxation, 69 lateral luxation and 8 intrusive
      luxation) were followed up for a minimum of 24 months. The time elapsed between
      dental trauma and the initial attendance was recorded. The presence of necrotic
      pulp and external inflammatory resorption for each type of trauma was verified.
      Fisher's exact test was used to verify the influence of the initial attendance
      date at the Dental Trauma Center and the development of inflammatory resorption
      (p<0.05). The odds ratio was used to check the risk of developing external
      inflammatory resorption due to delay in seeking treatment. Pulp necrosis was
      observed in 105 teeth (78.9%) and external inflammatory resorption was detected
      in 17.8% cases of extrusive luxation (10 teeth), 15.9% of lateral luxation (11
      teeth) and 25% of intrusive luxation (2 teeth). For lateral luxation, extended
      delay between the date of injury and initial attendance influenced the occurrence
      of external inflammatory resorption (p=0.0174). Patients who began treatment 45
      days after the injury were 3.4 times more likely to develop external inflammatory
      resorption than patients who sought treatment after the trauma. Treatment late
      after the occurrence of dental trauma can impair the prognosis and result in the
      development of external inflammatory resorption in luxated teeth.

PMID- 28492751
TI  - Influence of Thermal Cycles Number on Bond Strength of Metallic Brackets to
      Ceramic.
AB  - The aim of this study was to evaluate the effect of different number of thermal
      cycles on the shear bond strength (SBS) of metallic orthodontic brackets bonded
      to feldspathic ceramic by a composite resin. Twenty-five ceramic cylinders were
      etched with 10% hydrofluoric acid for 60 s and received two layers of silane.
      Brackets were bonded to the cylinders using Transbond XT and assigned to 5 groups
      (n=5): Group 1 - Control group (without thermal cycling); Group 2 - 500 thermal
      cycles; Group 3 - 5,000 thermal cycles; Group 4 - 7,000 thermal cycles and Group
      5 - 10,000 thermal cycles. Light-activation was carried out by Radii Plus LED.
      SBS testing was carried out after 24 h of storage in deionized water and thermal
      cycling (5/55 oC and 30 s dwell time). Five brackets were bonded to each
      cylinder, totalizing 25 brackets for each group. Data were submitted to one-way
      ANOVA and Tukey's test (alpha=0.05). The Adhesive Remnant Index (ARI) was
      evaluated at 8* magnification. The SBS (MPa) of control group (9.3+/-0.8), 500
      (9.0+/-0.7) and 5,000 (8.4+/-0.9) thermal cycles were significantly higher than
      those after 7,000 (6.8+/-0.6) and 10,000 (4.9+/-1.0) thermal cycles (p<0.05). The
      ARI showed a predominance of Scores 0 (adhesive failure) prevailed in all groups,
      as shown by the ARI, with increased scores 1 and 2 (mixed failures) for control
      group and 500 thermal cycles. In conclusion, thermal fatigue may compromise the
      bonding integration between metallic brackets and ceramic restorations. For in
      vitro testing, use of at least 7,000 cycles is advised to result in significant
      fatigue on the bonding interface.

PMID- 28492752
TI  - Effect of Metal Primers on Bond Strength of a Composite Resin to Nickel-Chrome
      Metal Alloy.
AB  - This study evaluated the effects of three metal primers and one multi-mode
      adhesive system on the shear bond strength (SBS) of a flowable composite resin to
      nickel-chrome metal alloy (Ni-Cr). Ninety plates were cast from Ni-Cr and divided
      in nine groups (n=10). The surfaces were sandblasted with Al2O3 and primed with
      three adhesive primers: Alloy Primer (AP), Universal Primer (TP) and RelyX
      Ceramic Primer (CP), and a multi-mode adhesive (Scotchbond Universal, SU). The
      Adper Single Bond Plus (SB) and SU adhesives were also combined with adhesive
      primers. Control group did not have any surface treatment. The groups were: AP,
      AP+SB, AP+SU, TP+SB, TP+SU, CP+SB, CP+SU and SU. Composite cylinders were built
      on alloy surface. After 24 h, half the specimens were subjected to SBS and the
      other half to thermal cycling before testing. Data were analyzed by two-way ANOVA
      and Tukey's test (a=0.05). Failure modes were assessed by SEM observation. Higher
      SBS were obtained with AP and TP combined with adhesives at 24 h and the lowest
      one for control group. Thermocycling reduced SBS for AP, CP+SU and SU.
      Combination between TP and SU resulted in the highest SBS after the
      thermocycling. TP groups showed all types of failures and high incidence of mixed
      failures. The use of AP and UP metal primers before application of SU and SB
      adhesive systems increased the SBS of composite to Ni-Cr. These combinations
      between metal primers and adhesives had the highest SBS after thermocycling.

PMID- 28492753
TI  - Effect of Erosion/Abrasion Challenge on the Dentin Tubule Occlusion Using
      Different Desensitizing Agents.
AB  - The aim of the study was to evaluate dentinal tubule occlusion, measuring the
      dentin permeability (Lp) and using different desensitizing agents before and
      after abrasive/erosive challenge. Dentin discs from 42 healthy human third molars
      were obtained. Minimum Lp was measured after a smear layer simulation using #600
      SiC paper and maximum Lp after an immersion in 0.5 M EDTA. The specimens were
      treated with different desensitizers: two varnishes (Clinpro XT Varnish-CV, Fluor
      Protector-FP), a paste (Desensibilize Nano P-NP) and a gel (Oxa Gel-OG). The Lp
      of each specimen was measured immediately after the desensitizers' application.
      The discs were subjected to erosion/abrasion cycles for 7 days, with 0.5% citric
      acid solution (6x/day) and tooth brushing (3x/day). Lp was measured after the
      first, fourth and seventh day of the challenge. The data were analyzed by 3-way
      ANOVA with repeated measurements and by a Games-Howell test (alpha=5%). FP and CV
      did not show significant differences in Lp immediately after application until
      the 7th day (p<0.05). OG showed a significant increase in Lp after the 4th and
      7th days. NP resulted in a significantly higher permeability compared to the
      other materials immediately after the application and after the 1st day of
      challenge. All the desensitizers reduced the dentin permeability immediately
      after application. However, only the varnishes were able to maintain the
      occlusive effect after the erosion/abrasion challenge.

PMID- 28492754
TI  - Mandibular Protraction Appliance Effects in Class II Malocclusion in Children,
      Adolescents and Young Adults.
AB  - The aim of this study was to evaluate the effects of the mandibular protraction
      appliance (MPA) for treating mild to moderate Class II malocclusion at different
      stages of dentofacial development. Lateral radiographs were evaluated before (T0)
      and at the end (T1) of orthodontic treatment with fixed appliance associated with
      MPA. Sixty-five consecutively treated patients were divided according to the
      stage of dentofacial development: 21 children in late mixed dentition, 22
      adolescents and 22 young adults with full permanent dentition. The differences
      between and within groups were analyzed by MANOVA at p<0.05. The correction of
      anteroposterior discrepancy (Wits) was significantly reduced in all development
      stages (p<0.01), with no difference between groups. Class II was corrected
      predominantly by dental changes in the mandibular arch, with accentuated
      proclination of the mandibular incisors and mesial displacement of mandibular
      molars. The MPA had no skeletal effects in any of the groups, except for a mild
      reduction of SNA (p=0.018) and ANB angles (p<0.0001) among the mixed dentition
      children. With regard to soft-tissue profile, facial convexity decreased
      significantly in all groups (p<0.01). In conclusion, the MPA associated with
      fixed appliance corrected the Class II occlusion, basically by a mandibular arch
      protrusion. A mild skeletal maxillary change was significant only when this
      treatment protocol began during mixed dentition.

PMID- 28492755
TI  - Association between Root Caries and Depressive Symptoms among Elders in Carlos
      Barbosa, RS, Brazil.
AB  - : The aim of this study was to evaluate the association between depressive
      symptoms and root caries among independent-living older persons. All community
      dwelling older adults (not hospitalized and not bedridden) living in Carlos
      Barbosa, RS, Brazil, were invited to participate, and 785 completed the study
      protocol (standardized questionnaire assessing socio-demographic information and
      health behavior, Geriatric Depression Scale [GDS] - brief version, and oral
      examination [DMFT-Root index, Visible Plaque Index and stimulated salivary
      flow]). Out of them, 390 participants with at least one natural tooth were
      included in the present analysis. The outcome of interest was the ratio between
      the number of decayed roots and the number of roots at risk. The association
      between independent variables (depression and socioeconomic aspects) and the
      outcome was assessed using negative binomial regression models. RESULTS: The
      final, fully adjusted model revealed that age (beta=0.03, p=0.001), female sex
      (beta=-0.23, p=0.08), living in a rural area (beta=0.25, p=0.008), tooth brushing
      frequency (beta=0.43, p=0.025) and stimulated salivary flow (beta=-0.012,
      p<0.0001) were significantly associated with the presence of root caries. In
      addition, the interaction between male sex and the presence of depression
      symptoms (beta=-0.99, p=0.012) was also independently and significantly
      associated with root caries. The interaction between male sex and depression
      symptoms was associated with root caries, suggesting that psychological
      mechanisms may be involved indirectly in the development of root caries in older
      adults.

PMID- 28492756
TI  - A Longitudinal Study of Early Childhood Caries and Associated Factors in
      Brazilian Children.
AB  - Early childhood caries (ECC) affects children all over the world and has high
      prevalence and severity in preschool children. Different social, biological and
      behavioral factors compose a network of causal factors for ECC. The aim was to
      evaluate the association between socioeconomic variables and caries at baseline,
      and the presence of Streptococcus mutans and Lactobacillus spp. microorganisms
      with the progression of caries lesions after two years of follow-up in a group of
      children. At baseline, 163 children (3-4 years old) living in the areas of 12
      primary care services of the Hospital Group Conceicao (GHC, Porto Alegre, RS,
      Brazil) were evaluated. After two years, 119 children were re-evaluated. Clinical
      examinations were conducted by calibrated examiners using the ICDAS criteria. A
      sociodemographic questionnaire was applied to the children's parents and saliva
      samples were collected from the children for microbiological analysis.
      Descriptive statistics and multivariate Poisson regression analysis were
      performed in the statistical analysis. The factors associated with the caries
      progression were marital status of mothers (p=0.040), higher S. mutans counts
      (p=0.031) and the presence of cavitated lesions at baseline (p<0.001). The caries
      lesions progression in preschool children enrolled in primary health care was
      directly associated with marital status, presence of cavitated lesions at
      baseline and higher S. mutans counts at two-year follow-up.

PMID- 28492757
TI  - Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats.
AB  - This study evaluated the action of ionizing radiation and the possible
      radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on
      the bone physiology of rat mandibles by assessing the alveolar socket healing and
      bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control
      (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2
      mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were
      irradiated with 15 Gy radiation dose in the mandible. Forty days after the above
      procedures, the mandibular first molars were extracted and the animals were
      killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were
      used to evaluate alveolar socket healing and bone strength, respectively. At 15
      days, bone volume, bone volume fraction and trabecular thickness were higher in
      the CG and MG than in the IG and MIG; and trabecular separation was higher in the
      IG compared with the others. At 30 days, there was a difference only in
      trabecular separation, which was higher in IG than in CG and MG, and MIG did not
      differ from the others. Bone strength was lower in IG compared with CG and MG,
      and MIG did not differ from the others. In conclusion, the ionizing radiation
      affected the bone physiology of rat mandibles, delaying the alveolar socket
      healing and reducing the bone strength. Moreover, the meloxicam had a positive
      effect on the trabecular separation in alveolar socket healing and on the bone
      strength.

PMID- 28492758
TI  - Giant Epignathus Teratoma Discovered at Birth: A Case Report and 7-Year Follow
      Up.
AB  - Teratomas are tumors composed by tissues derived from the three germ cell layers,
      and they are relatively uncommon in head and neck. The term epignathus has been
      applied to teratomas from the oropharynx. This paper reports the case of a giant
      epignathus teratoma discovered at birth, which was successfully managed and
      followed up for 7 years. A newborn boy presented a polypoid tumor mass
      exteriorizing through the mouth over a length of 9 cm, with some surface areas
      resembling skin and others exhibiting hair. Computed tomography showed that the
      mass arose deep from the left hemiface. Alpha-fetoprotein (AFP) levels were high
      (316,000 ng/mL). Surgery was performed and microscopic analysis confirmed the
      diagnosis of mature teratoma. Because of residual tumor and high AFP levels, the
      patient was submitted to chemotherapy, resulting in complete regression of the
      lesion and normalization of AFP levels. Surgical repair of a cleft palate was
      performed at 5 years of age. At 7 years of age, the patient was in good general
      health and showed no clinical signs of recurrence. Although epignathus is a rare
      condition, it should be diagnosed in the fetus as early as possible. Prenatal
      care provides unquestionable benefits, providing the early diagnosis of anomalies
      that can jeopardize the life of the fetus and contributing to the indication of
      cases that require treatment before birth.

PMID- 28492759
TI  - Ameloblastic Fibrosarcoma: A Case Report and Literature Review.
AB  - Here is described a case of ameloblastic fibrosarcoma (AFS) affecting the
      posterior mandible of a woman who was treated surgically and recovered without
      signs of recurrence or metastasis after 12 years of follow-up. Tumor sections
      were immunostained for cell cycle, epithelial and mesenchymal markers.
      Immunohistochemical analysis evidenced high Ki-67 positivity in stromal cells
      (mean of 20.9 cells/High power field). Epithelial cells displayed strong
      positivity for p53, p63 and cytokeratin 19. In addition to the case report, a
      systematic review of current knowledge is presented on the AFS's clinical
      demographic features and prognostic factors. Based on the review, 88/99 cases
      were diagnosed as AFS, 9/99 as ameloblastic fibro-odontosarcoma and 2/99 as
      ameloblastic fibrodentinosarcoma. All these lesions displayed very similar
      clinical-demographic and prognostic features. Moreover, the review provided
      evidence that first treatment, regional metastasis, distant metastasis and local
      recurrence were significant prognostic values for malignant odontogenic
      mesenchymal lesions. Based on the findings, segregation among ameloblastic
      fibrosarcoma, ameloblastic fibrodentinosarcoma and ameloblastic fibro
      odontosarcoma seems illogical, considering all these lesions have similar
      predilections and outcomes.

PMID- 28492760
TI  - Determinants of tobacco use by students.
AB  - OBJECTIVE: Estimate the prevalence and determinants of tobacco use by students.
      METHODS: This cross-sectional study, carried out between 2013 and 2014, evaluates
      701 public school students between 10 and 79 years of age living in a city in the
      countryside of the State of Goias, Midwest of Brazil. A structured questionnaire
      collected the data and the predictor variables were demographic data, family
      nucleus, religion, physical activity practice, family functionality and parental
      smoking. Two multivariable models were implemented, the first for occasional
      tobacco use and the second for regular use, acquiring the measure of prevalence
      ratio (PR) and their respective 95%CI. Variables with p < 0.10 were included in
      Poisson regression models with robust variance to obtain the adjusted PR (adPR)
      and 95%CI. The Wald Chi-Squared test examined the differences between
      proportions, and values with p < 0.05 were statistically significant. RESULTS:
      The prevalence of occasional and regular tobacco use were 33.4% (95%CI 29.8-36.9)
      and 6.7% (95%CI 5.0-8.8), respectively. The factors associated with occasional
      tobacco consumption were age of 15 to 17 years (adPR = 1.98) and above 18 years
      (adPR = 3.87), male gender (adPR = 1.23), moderate family dysfunction (adPR =
      1.30), high family dysfunction (adPR = 1.97) and parental smoking (adPR = 1.60).
      In regards to regular consumption of tobacco, age above 18 years (adPR = 4.63),
      lack of religion (adPR = 2.08), high family dysfunction (adPR = 2.35) and
      parental smoking (adPR = 2.89) remained associated. CONCLUSIONS: Students exhibit
      a high prevalence of occasional and regular tobacco use. This consumption relates
      to sociodemographic variables and family dysfunction. OBJETIVO: Estimar a
      prevalencia e determinantes do consumo de tabaco por estudantes. METODOS: Neste
      estudo de corte transversal, realizado entre 2013 e 2014, avaliamos 701
      estudantes entre 10 e 79 anos de escolas publicas de um municipio do interior do
      estado de Goias, Centro-Oeste do Brasil. Os dados foram coletados por meio de um
      questionario estruturado, cujas variaveis preditoras foram: dados
      sociodemograficos, nucleo familiar, religiao, pratica de atividade fisica,
      funcionalidade familiar e pai ou mae fumante. Foram implementados dois modelos
      multivariaveis, o primeiro para uso de tabaco na vida e o segundo para uso
      regular, obtendo-se como medida de efeito razao de prevalencia (RP) e seus
      respectivos IC95%. Variaveis com p < 0,10 foram incluidas em modelos de regressao
      de Poisson com variancia robusta, para obtencao da RP ajustada (RPaj) e IC95%. O
      teste Qui-quadrado de Wald foi utilizado para testar as diferencas entre as
      proporcoes, e valores com p < 0,05 foram considerados estatisticamente
      significantes. RESULTADOS: As prevalencias de consumo de tabaco na vida e regular
      foram de 33,4% (IC95% 29,8-36,9) e 6,7% (IC95% 5,0-8,8), respectivamente. Os
      fatores associados ao consumo de tabaco na vida foram: idade de 15 a 17 anos
      (RPaj = 1,98) e superior a 18 anos (RPaj = 3,87), sexo masculino (RPaj = 1,23),
      moderada disfuncionalidade familiar (RPaj = 1,30), elevada disfuncionalidade
      familiar (RPaj = 1,97) e pai ou mae fumante (RPaj = 1,60). Em relacao ao consumo
      regular de tabaco, permaneceram associados a idade superior a 18 anos (RPaj =
      4,63), nao possuir religiao (RPaj = 2,08), elevada disfuncionalidade familiar
      (RPaj = 2,35) e pai ou mae fumante (RPaj = 2,89). CONCLUSOES: Estudantes
      apresentam elevada prevalencia de consumo de tabaco na vida e regular. Esse
      consumo associa-se com variaveis sociodemograficas e disfuncionalidade familiar.

PMID- 28492761
TI  - Hospitalization in older adults: association with multimorbidity, primary health
      care and private health plan.
AB  - OBJECTIVE: Evaluate the association of multimorbidity, primary health care model
      and possession of a private health plan with hospitalization. METHODS: A
      population-based cross-sectional study with 1,593 elderly individuals (60 years
      old or older) living in the urban area of the city of Bage, State of Rio Grande
      do Sul, Brazil. The outcome was hospitalization in the year preceding the
      interview. The multimorbidity was evaluated through two cut-off points (>= 2 and
      >= 3). The primary health care model was defined by residence in areas covered by
      traditional care or by Family Health Strategy. The older adults mentioned the
      possession of a private health plan. We performed a gross and adjusted analysis
      by Poisson regression using a hierarchical model. The adjustment included
      demographic, socioeconomic, functional capacity disability and health services
      variables. RESULTS: The occurrence of overall and non-surgical hospitalization
      was 17.7% (95%CI 15.8-19.6) and 10.6% (95%CI 9.1-12.1), respectively. Older
      adults with multimorbidity were admitted to hospitals more often when to older
      adults without multimorbidity, regardless of the exhibition' form of operation.
      Having a private health plan increased the hospitalization by 1.71 (95%CI 1.09
      2.69) times among residents in the areas of the Family Health Strategy when
      compared to elderly residents in traditional areas without a private health plan.
      CONCLUSIONS: The multimorbidity increased the occurrence of hospitalizations,
      especially non-surgical ones. Hospitalization was more frequent in older adults
      with private health plan and those living in Family Health Strategy areas,
      regardless of the presence of multiple diseases. OBJETIVO: Avaliar a associacao
      da multimorbidade, modelo de atencao basica e posse de plano de saude com
      hospitalizacao. METODOS: Estudo transversal de base populacional com 1.593 idosos
      (60 anos ou mais) residentes na zona urbana do municipio de Bage, Rio Grande do
      Sul. O desfecho foi a hospitalizacao no ano anterior a entrevista. A
      multimorbidade foi avaliada por meio de dois pontos de corte (>= 2 e >= 3). O
      modelo de atencao basica foi definido pela residencia em areas cobertas pela
      atencao tradicional ou da Estrategia Saude da Familia. A posse de plano de saude
      foi referida pelos idosos. Realizou-se analise bruta e ajustada por regressao de
      Poisson utilizando modelo hierarquizado. O ajuste incluiu variaveis demograficas,
      socioeconomicas, capacidades funcionais e de servicos de saude. RESULTADOS: A
      ocorrencia de hospitalizacao geral e nao cirurgica foi de 17,7% (IC95% 15,8-19,6)
      e 10,6% (IC95% 9,1-12,1), respectivamente. Idosos com multimorbidade
      hospitalizaram mais em comparacao com os idosos sem multimorbidade,
      independentemente da forma de operacionalizacao da exposicao. O plano de saude
      aumentou em 1,71 (IC95% 1,09-2,69) vezes a internacao hospitalar entre residentes
      nas areas da Estrategia Saude da Familia em comparacao aos idosos residentes nas
      areas tradicionais sem plano de saude. CONCLUSOES: A multimorbidade aumentou a
      ocorrencia de hospitalizacoes, principalmente aquelas nao cirurgicas. Idosos com
      plano de saude e residentes em areas de Estrategia Saude da Familia internaram
      mais, independentemente da presenca de multiplas doencas.

PMID- 28492762
TI  - Equity in out-of-pocket payment in Chile.
AB  - OBJECTIVE: To assess the distribution of financial burden in Chile, with a focus
      on the burden and progressivity of out-of-pocket payment. METHODS: Based on the
      principle of ability to pay, we explore factors that contribute to inequities in
      the health system finance and issues about the burden of out-of-pocket payment,
      as well as the progressivity and redistributive effect of out-of-pocket payment
      in Chile. Our analysis is based on data from the 2006 National Survey on
      Satisfaction and Out-of-Pocket Payments. RESULTS: Results from this study
      indicate evidence of inequity, in spite of the progressivity of the healthcare
      system. Our analysis also identifies relevant policy variables such as education,
      insurance system, and method of payment that should be taken into consideration
      in the ongoing debates and research in improving the Chilean system. CONCLUSIONS:
      In order to reduce the detected disparities among income groups, healthcare
      priorities should target low-income groups. Furthermore, policies should explore
      changes in the access to education and its impact on equity.

PMID- 28492763
TI  - Sociodemographic and health factors associated with mortality in community
      dwelling elderly.
AB  - OBJECTIVE: The objective of this study is to identify factors associated with
      mortality, with emphasis on gender and age differences. METHODS: This is a cross
      sectional study, which uses data from the FIBRA-2008-2009 network in Campinas,
      State of Sao Paulo, Brazil, with information on non-institutionalized residents
      of the urban area and the Mortality Information System. The dependent variable
      has been death, in 2013. The associations have been tested by odds ratio (OR) and
      their 95% confidence intervals, and the analyses have been conducted using the
      program Stata 12.0. RESULTS: Average age has been 72.3 years, 69.3% have been
      women, and 8.9% have died. We have found greater OR for mortality in individuals
      aged >= 75 years, classified as pre-frail or frail, and in those who have
      reported heart disease. CONCLUSIONS: In this study, the analysis of specific
      subgroups has allowed us to better understand the relationship between the
      factors associated with death in the elderly. With the exception of age,
      strategies based on primary and secondary care, focused on priority groups, can
      have a positive impact on the reduction of mortality among the elderly. OBJETIVO:
      Identificar fatores associados a mortalidade, com enfase nas diferencas de genero
      e idade. METODOS: Trata-se de estudo transversal, utilizando dados provenientes
      da rede FIBRA-2008-2009 em Campinas, SP, com informacoes de pessoas nao
      institucionalizadas residentes na area urbana e pelo Sistema de Informacoes de
      Mortalidade. A variavel dependente foi a ocorrencia de obito, verificada em 2013.
      As associacoes foram testadas pelas razoes de chances (OR) e respectivos
      intervalos de confianca de 95%, e as analises conduzidas no programa Stata 12.0.
      RESULTADOS: A media de idade foi 72,3 anos, 69,3% eram mulheres e 8,9% foram a
      obito. Encontrou-se maior OR para mortalidade nos individuos com idade >= 75
      anos, nos classificados como pre-fragil ou fragil e naqueles que referiram doenca
      do coracao. CONCLUSOES: Neste estudo, a analise para os subgrupos especificos
      permitiu melhor compreender a relacao entre fatores que se associam ao obito no
      idoso. Com excecao da idade, estrategias baseadas no cuidado especifico de
      atencao primaria e secundaria, direcionadas a grupos prioritarios, podem ter um
      impacto positivo na reducao da mortalidade entre os idosos.

PMID- 28492765
TI  - Epidemiology and Health Services: journal of the Brazilian National Health System
      is classified B2 for Public Health at Qualis/Capes.

PMID- 28492764
TI  - Measuring the quality of life in hypertension according to Item Response Theory.
AB  - OBJECTIVE: To analyze the Miniquestionario de Qualidade de Vida em Hipertensao
      Arterial (MINICHAL - Mini-questionnaire of Quality of Life in Hypertension) using
      the Item Response Theory. METHODS: This is an analytical study conducted with 712
      persons with hypertension treated in thirteen primary health care units of
      Fortaleza, State of Ceara, Brazil, in 2015. The steps of the analysis by the Item
      Response Theory were: evaluation of dimensionality, estimation of parameters of
      items, and construction of scale. The study of dimensionality was carried out on
      the polychoric correlation matrix and confirmatory factor analysis. To estimate
      the item parameters, we used the Gradual Response Model of Samejima. The analyses
      were conducted using the free software R with the aid of psych and mirt. RESULTS:
      The analysis has allowed the visualization of item parameters and their
      individual contributions in the measurement of the latent trait, generating more
      information and allowing the construction of a scale with an interpretative model
      that demonstrates the evolution of the worsening of the quality of life in five
      levels. Regarding the item parameters, the items related to the somatic state
      have had a good performance, as they have presented better power to discriminate
      individuals with worse quality of life. The items related to mental state have
      been those which contributed with less psychometric data in the MINICHAL.
      CONCLUSIONS: We conclude that the instrument is suitable for the identification
      of the worsening of the quality of life in hypertension. The analysis of the
      MINICHAL using the Item Response Theory has allowed us to identify new sides of
      this instrument that have not yet been addressed in previous studies. OBJETIVO:
      Analisar o Miniquestionario de Qualidade de Vida em Hipertensao Arterial
      (MINICHAL) por meio da Teoria da Resposta ao Item. METODOS: Estudo analitico
      realizado com 712 pessoas com hipertensao arterial atendidas em 13 unidades de
      atencao primaria em saude de Fortaleza, CE, em 2015. As etapas da analise pela
      Teoria da Resposta ao Item foram: avaliacao da dimensionalidade, estimacao dos
      parametros dos itens e construcao da escala. O estudo da dimensionalidade foi
      realizado sobre a matriz de correlacao policorica e analise fatorial
      confirmatoria. Para a estimacao dos parametros dos itens, foi utilizado o Modelo
      de Resposta Gradual de Samejima. As analises foram conduzidas no software livre R
      com o auxilio dos pacotes psych e mirt. RESULTADOS: A analise permitiu a
      visualizacao dos parametros dos itens e suas contribuicoes individuais na
      mensuracao do traco latente, gerando mais informacao, permitindo a construcao de
      uma escala com um modelo interpretativo que demonstra a evolucao da piora da
      qualidade de vida em cinco niveis. Quanto aos parametros dos itens, houve bom
      desempenho daqueles referentes ao estado somatico, pois apresentaram melhor poder
      de discriminar os individuos com pior qualidade de vida. Os itens relacionados ao
      estado mental foram os que contribuiram com menor quantidade de informacao
      psicometrica no MINICHAL. CONCLUSOES: Conclui-se que o instrumento e indicado
      para a identificacao da deterioracao da qualidade de vida em hipertensao
      arterial. A analise do MINICHAL pela Teoria da Resposta ao Item permitiu
      identificar novas facetas desse instrumento ainda nao abordadas em estudos
      anteriores.

PMID- 28492766
TI  - Clinical-epidemiological description of live births with microcephaly in the
      state of Sergipe, Brazil, 2015.
AB  - OBJECTIVE: to describe the clinical and epidemiological characteristics of
      microcephaly cases in live births in Sergipe, Brazil, and to calculate the
      prevalence in its municipalities. METHODS: this is a descriptive study on live
      births from September 1st to November 30th, 2015, with data from medical records
      and interviews with mothers. RESULTS: 83 cases of microcephaly were confirmed,
      with three deaths; prevalence in the 26 municipalities with confirmed cases
      ranged from 18 to 185/10,000 live births; the median of head circumference was 31
      cm (range: 22.5-33.0); agenesis of corpus callosum (26/43), lissencephaly
      (12/43), absence of midline (10/43) and ventriculomegaly (8/43) were observed in
      the transfontanellar ultrasound; 40 mothers reported rash in pregnancy, 23 in the
      first trimester, with pruritus, arthralgia and headache; seven were positive for
      infections potentially causing malformations. CONCLUSION: there was a high
      occurrence of cases of microcephaly, and reports of signs and symptoms compatible
      with Zika virus infection during pregnancy.

PMID- 28492767
TI  - Syphilis in pregnancy and congenital syphilis in Palmas, Tocantins State, Brazil,
      2007-2014.
AB  - OBJECTIVE: to describe the epidemiological profile of reported cases of syphilis
      in pregnant women and congenital syphilis in the period 2007-2014 in Palmas-TO,
      Brazil. METHODS: this is a descriptive study with data from the Information
      System for Notifiable Diseases (Sinan). RESULTS: 171 pregnant women with syphilis
      (4.7/1,000 live births [LB]) and 204 cases of congenital syphilis (5.6/1,000 LB)
      were identified; most women were brown-skinned (71.3%), had low education level
      (48.0%) and received late diagnosis during prenatal care (71.9%); the incidence
      of congenital syphilis varied from 2.9 to 8.1/1,000 LB in the period; the
      predominant maternal characteristics were age from 20 to 34 years (73.5%), having
      up to complete high school (85.3%), attending prenatal care (81.4%), diagnosis of
      syphilis during prenatal care (48.0%), and untreated partners of mothers who
      attended prenatal care (83.0%), reaching almost 80% of live births with
      congenital syphilis. CONCLUSION: it is necessary to adopt new strategies for the
      effectiveness of the prenatal care provided, and, consequently, to reduce the
      incidence of congenital syphilis.

PMID- 28492768
TI  - Coverage trends of the Information System on Live Births in Mato Grosso, Brazil,
      2000 to 2012.
AB  - OBJECTIVE: to analyze the coverage trends of the Brazilian Information System on
      Live Births (Sinasc) in the state of Mato Grosso and its Health Regions, in the
      period from 2000 to 2012. METHODS: this is a time series study, coverage was
      calculated by the ratio between the number of live births registered in the
      system and the number estimated by the Brazilian Institute of Geography and
      Statistics (IBGE); the trends were analyzed using polynomial regression models.
      RESULTS: Sinasc coverage in Mato Grosso in the studied period presented
      increasing trend, with a median of 94.9%; Araguaia Xingu region presented
      coverage lower than 90% in the period; most of the regions presented coverage
      increasing trends, except for Baixada Cuiabana, Centro Norte and Vale do Peixoto.
      CONCLUSION: Sinasc coverage in Mato Grosso was satisfactory and has been
      increasing in most of Health Regions.

PMID- 28492769
TI  - Census of the Primary Health Care structure in Brazil (2012): potential coverage
      estimates.
AB  - OBJECTIVE: to estimate and discuss selected indicators of Primary Health Care
      (PHC) structure in Brazil in 2012. METHODS: a descriptive ecological study was
      carried out using Primary Health Care Centre census data from the National
      Program for Access and Quality Improvement in Primary Care (PMAQ-AB); potential
      coverage indicators were estimated for infrastructure, health team composition
      and services available. RESULTS: the results revealed high coverage (>=70%) in
      Brazil for Community Health Agents (87.6%), teams providing care 5 days or more a
      week (71.4%), in 2 or more daily periods (70%), with nursing care services
      (70.9%) and dressing changes (70.4%); on the other hand, coverage is still poor
      (<=30%) for teams in health centres with adequate external signage (25.4%),
      delivering care at the weekend (28.4%) and reception of service users by health
      professionals (10.4%). CONCLUSION: the findings of this study point to the great
      inequalities between Brazilian states in potential coverage as shown by APS
      structure indicators.

PMID- 28492770
TI  - Descriptive study on the evolution of hospitalization costs for ambulatory care
      sensitive conditions in Brazil, 2000-2013.
AB  - OBJECTIVE: to analyze the proportions of costs of hospitalizations for ambulatory
      care sensitive conditions (ACSC) in relation to total hospitalization costs
      funded by the Brazilian National Health System (SUS) in Brazil, in 2000, 2005,
      2010 and 2013, according to sex, age and group of causes. METHODS: this is a
      descriptive study, with data from SUS Hospital Information System (SIH/SUS); the
      proportion of hospitalization costs for ACSC was estimated in relation to total
      hospitalization costs. RESULTS: proportions decreased from 23.6% (2000) to 17.4%
      (2013); higher rates occurred among women (29.8%), children (42.3%) and the
      elderly (31.7%); on the other hand, there was a significant increase in the
      proportion of hospitalization costs for angina (237.5%) and pneumonia (84.3%).
      CONCLUSION: there were greater reductions in costs among children, elderly and
      women; however, the persistence of high proportion of costs attributed to
      cardiovascular diseases stands out, especially hospitalizations for angina.

PMID- 28492771
TI  - Functional disability indicators and associated factors in the elderly: a
      population-based study in Bage, Rio Grande do Sul, Brazil.
AB  - OBJECTIVE: to estimate the prevalence of functional disability in basic and
      instrumental daily activities and associated factors in elderly who live in the
      urban area of Bage-RS, Brazil. METHODS: this is a population-based cross
      sectional study, conducted in 2008; functional disability was defined by basic
      and instrumental daily activities, using Katz index and Lawton and Brody scale;
      Poisson regression was used for crude and adjusted analyses. RESULTS: 1,593
      elderly individuals were investigated; the prevalence of disability for basic
      activities was of 10.6% (95%CI: 9.1;12.1) and of 34.2% (95%CI: 31.9;36.6) for
      instrumental activities; both disabilities were statistically associated to the
      increment of age, low education level, alcohol consumption, history of
      cerebrovascular diseases, cognitive impairment, hospitalization and home care.
      CONCLUSION: a high proportion of elderly presented functional disability; the
      outcomes were associated to the following variables: demographic, socioeconomic,
      behavioral, health status and use of health services.

PMID- 28492772
TI  - Life and health conditions among elderly: results of the EpiFloripa Idoso cohort
      study.
AB  - OBJECTIVE: to identify sociodemographic, behavioral and health changes in a
      follow-up of participants in the health survey EpiFloripa Idoso. METHODS: this is
      a population-based longitudinal study with elderly individuals in Florianopolis
      SC, Brazil. RESULTS: 1,702 elderly individuals were interviewed in 2009-2010 and
      1,197 in 2013-2014 (response rate: 89.1% and 70.2%, respectively); among followed
      up individuals, most of them remained with a partner (53.4%), living with other
      people (76.0%), not working (78.0%), with positive health perception (44.0%), not
      using the Internet (67.5%), not smoking (57.5%), not consuming alcohol (53.3%),
      not physically active (56.3%), consuming <5 servings of fruits/vegetables
      (57.3%), independent (60.5%), overweight (47.0%), with negative screening for
      cognitive impairment (69.4%), with no depressive symptoms (72.0%) and not having
      suffered falls (60.6%). CONCLUSION: most elderly did not show significant changes
      in their sociodemographic, behavioral and health characteristics; the need to
      rethink more effective actions to improve the elderly health stands out.

PMID- 28492773
TI  - Prevalence and associated factors of self-medication in adults living in the
      Federal District, Brazil: a cross-sectional, population-based study.
AB  - OBJECTIVE: to assess the prevalence of self-medication and to investigate its
      associated factors in adults living in the Federal District, Brazil. METHODS:
      this is a cross-sectional population-based study conducted with adults selected
      through probabilistic sampling; self-medication prevalence was obtained from
      those who reported having used any medicine in the previous seven days; Poisson
      regression model with robust variance was applied to adjust the prevalence
      ratios. RESULTS: 1,820 individuals were interviewed, of which 646 had taken at
      least one medicine; self-medication prevalence was of 14.9% (95%CI: 12.6%;17.5%);
      the adjusted analysis showed negative association in people aged 50 to 65 years
      (PR=0.26; 95%CI: 0.15;0.47) and with chronic diseases (PR=0.38; 95%CI:
      0.28;0.51); adults with difficulties in performing daily activities (PR=2.25;
      95%CI: 1.43;3.53) practiced more self-medication. CONCLUSION: self-medication was
      associated to young adults and those with problems in performing daily
      activities.

PMID- 28492774
TI  - The burden of cardiovascular diseases in Santa Catarina State, Brazil, in 2009.
AB  - OBJECTIVE: to estimate the burden of cardiovascular diseases in Santa Catarina
      State, Brazil. METHODS: this is an ecological study with the nine health
      macroregions of the state as units of analysis; the number of years of life lost,
      the number of years lived with disability and the number disability-adjusted life
      years (DALYs) for 2009 were estimated. RESULTS: a total of 358,777 DALYs were
      estimated, with a rate of 5,852 DALYs/100,000 inhabitants, 51.1% in males; age
      groups with the highest rates were 45-59, 60-69, and 70-79 years; diseases that
      most contributed to the DALYs were ischemic heart diseases and cerebrovascular
      diseases; health regions with the highest DALYs rates were Planalto Norte, Sul
      and Serra Catarinense. CONCLUSION: the high burden of cardiovascular diseases in
      Santa Catarina shows the need to intensify actions of health promotion and
      prevention in all regions of the state.

PMID- 28492775
TI  - Laboratory Environment Management System - GAL: Assessment of a tool for sentinel
      surveillance of influenza-like illness, Brazil, 2011-2012.
AB  - OBJECTIVE: to evaluate the Brazilian Laboratorial Environment Management System
      (GAL) as a data source for the Sentinel Surveillance of Influenza-Like Illness
      (SSILI). METHODS: this is an evaluation study of GAL, through the analysis of its
      simplicity, flexibility, data quality, acceptability, representativeness,
      timeliness, stability and usefulness for SSILI, based on the guide for system
      evaluation in public health of the Centers for Disease Control and Prevention
      (Atlanta/GA, USA). RESULTS: in 2011 and 2012, a total of 13,765 exams for
      respiratory viruses were registered. GAL presented simple structure, flexibility
      to changes, good data quality, acceptability and timeliness in the access to test
      results, being representative and stable in 23 Brazilian states. CONCLUSION: the
      system is useful in meeting the goals of SSILI; however, there are some
      recommendations for adjustments and for encouraging the adherence by the states
      that do not use the system yet.

PMID- 28492776
TI  - Tuberculosis mortality in Brazilian capitals, 2008-2010.
AB  - OBJECTIVE: to analyze the association between tuberculosis mortality and socio
      demographics and health indicators in the capitals of Brazilian states and the
      Federal District. METHODS: this is an ecological study whose outcome was the
      standardized coefficient of tuberculosis mortality in the 2008-2010 period; the
      independent variables comprised 16 indicators, grouped into three blocks; Pearson
      correlation test and multiple linear regression were applied for analysis.
      RESULTS: 4,744 deaths from tuberculosis were registered in the 27 municipalities
      (2.7 deaths per 100,000 inhabitants); the following indicators were associated
      with tuberculosis mortality (p<0.10): income inequality (Gini index of monthly
      income of individuals over 10 years old: beta=0.454; 95%CI 6.21;28.51),
      proportion of migrants in the municipality (beta=0.537 95%CI 0.12;0.31), poor
      black-skinned individuals (beta=0.302 95%CI 0.004;0.109) and coefficient of
      Tb/HIV coinfection (beta=0.449 95%CI 0.05;0.28). CONCLUSION: tuberculosis
      mortality was higher in capitals with greater income inequality, migration,
      poverty among black-skinned individuals and occurrence of Tb/HIV coinfection.

PMID- 28492777
TI  - Tuberculosis and diabetes: probabilistic linkage of databases to study the
      association between both diseases.
AB  - OBJECTIVE: to describe the profile of cases of tuberculosis and diabetes
      comorbidity in Brazil. METHODS: this is a descriptive study with data from the
      Brazilian Information System for Notifiable Diseases - tuberculosis (Sinan-TB)
      and from the System of Registration and Monitoring of Hypertension and Diabetes
      Mellitus (Hiperdia), from 2007 to 2011; probabilistic linkage was carried out
      with Reclink software. RESULTS: 24,443 cases of comorbidity were found, including
      3,181 cases not registered on Sinan-TB; of the total number of recovered cases,
      mostly were males (57.2%), aged 40-59 years (52.3%), black/brown-skinned (68.4%),
      with five to eight years of schooling (78.4%), with no regular use of alcohol
      (86.5%) and negative serology for the HIV virus (91.8%). CONCLUSION: the cases
      found had similar profile to those registered on Sinan-TB and the probabilistic
      linkage of data from different information systems enabled the detection of cases
      not captured by surveillance.

PMID- 28492778
TI  - Sociodemographic, clinical and epidemiological aspects of Tuberculosis treatment
      abandonment in Pernambuco, Brazil, 2001-2014.
AB  - OBJECTIVE: to describe abandonment rates according to sociodemographic, clinical
      and epidemiological characteristics of new tuberculosis cases being treated in
      Pernambuco State, Brazil. METHODS: this is a descriptive ecological study using
      data from the Information System for Notifiable Diseases from 2001 to 2014; the
      abandonment rate was calculated by the Regional Administration on Health (GERES).
      RESULTS: of the 57,015 new cases, 6,474 (11.3%) abandoned treatment, although
      abandonment decreased from 16.4% (2001) to 9.3% (2014); the abandonment rate in
      GERES I Recife, III Palmares, IV Caruaru, VIII Petrolina and IX Ouricuri was
      still >5% in 2014; the rate was higher in males (11.9%), people aged 20-39
      (12.7%), people with incomplete elementary school (12.1%), black-skinned people
      (13.7%), institutionalized people (12.5%) and those with pulmonary +
      extrapulmonary tuberculosis (14.1%). CONCLUSION: despite the decrease, the
      abandonment rate remained high; males, adults with low education level, black
      skinned people, institutionalized patients and patients with pulmonary +
      extrapulmonary tuberculosis seemed more prone to abandoning treatment.

PMID- 28492779
TI  - Prevalence of Kaposi's sarcoma in patients with AIDS and associated factors, Sao
      Paulo-SP, Brazil, 2003-2010.
AB  - OBJECTIVE: to estimate the prevalence of Kaposi's sarcoma (KS) in patients with
      AIDS and identify the associated factors to the occurrence of this neoplasm.
      METHODS: this is a cross-sectional study with notification data from two AIDS
      reference centers in Sao Paulo-SP, Brazil, from January, 2003 to March, 2010;
      probabilistic linkage and multiple logistic regression methods were applied.
      RESULTS: among 3,557 AIDS cases, 213 (6%) presented KS; 95.3% of them occurred in
      males; male sex (OR=3.1; 95%CI=1.4;6.6), age at the AIDS diagnosis >28 years old
      (OR=1.6; 95%CI=1.0;2.6), MSM (OR=3.2; 95%CI=2.0;4.9), prior use of HAART (OR=0.4;
      95%CI=0.3;0.5), AIDS diagnosis between 2007-2010 (OR=0.3; 95%CI=0.2;0.4), and
      CD4+ T-cell counting under 200cells/mm3 (OR=16.0; 95%CI=6.0;42.7) and 200
      500cells/mm3 (OR=2,5; 95%CI=1.1;6.4) were associated to the occurrence of KS.
      CONCLUSION: KS has a high prevalence in Sao Paulo-SP; strategies for early HIV
      diagnosis may reduce this prevalence.

PMID- 28492780
TI  - [Epidemiological profile of traffic accidents in Marilia, Sao Paulo State,
      Brazil, 2012].
AB  - OBJECTIVE: to describe the profile of victims of traffic accidents and traffic
      related deaths in Marilia-SP, Brazil. METHODS: this is a descriptive study, based
      on data from police reports (PR) and Death Certificates (DC), in 2012. RESULTS:
      1,537 PR were gathered; among the 3,257 individuals involved in traffic
      accidents, 67.3% were men, and 53.3% were between 20-39 years of age; most
      accidents occurred on road intersections (35.2%), at 8 a.m. (6.8%), 1 p.m. (7.2%)
      and 7 p.m. (8.1%); motorcycle was the most involved vehicle in the accidents
      (47.6%); among the 78 deaths reported, 61 were men, 31 were over 50 years old,
      and 23 were motorcyclists; 32 fatal accidents occurred on highways. Conclusion:
      the main victims and fatal victims of traffic accidents were male motorcyclists;
      fatal accidents occurred mainly on highways, and the main victims were over 50
      years old.

PMID- 28492781
TI  - Evaluation of knowledge about the Human Papilloma Virus (HPV) and its vaccination
      among Community Health Agents in the municipality of Tubarao, Santa Catarina,
      Brazil, in 2014.
AB  - OBJECTIVE: to evaluate the knowledge of Community Health Agents (CHA) about the
      Human Papilloma Virus (HPV) and its vaccination. METHODS: this is a cross
      sectional study with CHA who worked in Tubarao-SC, Brazil, in 2014; data were
      collected through an evaluation tool about HPV and its vaccination, validated for
      English language and translated and adapted into Portuguese. RESULTS: 124 CHA
      participated in this study; all of them had already heard about HPV, but only
      25.0% had heard about HPV testing; 72.6% answered correctly less than 70.0% of
      the questions; those who answered correctly more than 70.0% were, in general,
      younger than the other CHA (p=0.010). CONCLUSION: CHA demonstrated little
      knowledge on HPV, which may affect their work as multipliers in the prevention of
      diseases and in education in health.

PMID- 28492782
TI  - [Outbreak of nephritis by Streptococcus equi subspecies zooepidemicus: case
      control study in the municipality of Monte Santo de Minas, Minas Gerais, Brazil,
      2013].
AB  - OBJECTIVE: to investigate an outbreak of nephritis by Streptococcus zooepidemicus
      in Monte Santo de Minas, Minas Gerais State, Brazil. METHODS: a case-control
      study and attempt to isolate the bacterial agent were carried out from January to
      April 2013, using clinical and laboratory data, interviews and inspections.
      RESULTS: 417 suspected cases were reported, of which 175 (42.0%) were confirmed;
      90.9% lived in that municipality, of which 67.4% were female, with median age of
      36 years; 24% of cases were hospitalized; three ice cream shops in the
      municipality used type A milk; there was significant association between the
      illness and the consumption of type A milk (odds ratio [OR]=4.16/95%CI:
      1.55;11.18), one of the ice cream made with this milk (OR=3.09/95%CI: 1.39;6.86)
      and milk shake of non-processed milk (OR=3.25/95%CI: 1.13;9.36); the bacterium
      was not detected in rural properties. CONCLUSION: the outbreak of nephritis by
      Streptococcus zooepidemicus was associated with the consumption of milk and dairy
      products.

PMID- 28492783
TI  - Infant mortality surveillance in Recife, Pernambuco, Brazil: operationalization,
      strengths and limitations.
AB  - OBJECTIVE: to report the experience on infant mortality surveillance (IMS) in the
      municipality of Recife-PE, Brazil. METHODS: a documentary research and a query
      with key-informants who participated in the implementation and consolidation of
      the IMS were conducted; data of the Mortality Information System (SIM) and of the
      surveillance worksheets were used to measure the coverage of the investigated
      deaths. RESULTS: the implementation of the IMS has occurred gradually since 2003;
      the strategy is composed by (i) identification of deaths, (ii) investigation,
      (iii) discussion, (iv) recommendations and correction of vital statistics; upon
      completion of implementation (2006), 98.5% (256) of the deaths had been
      investigated and discussed, with the participation of those involved in the
      cases; in 2015, this coverage corresponded to 97.7%. CONCLUSION: the main
      recommendations consisted of expanding the access, coverage and improvement of
      primary, secondary and tertiary care quality; IMS is able to support changes in
      health care practices, as well as planning and organization of maternal and child
      care.

PMID- 28492784
TI  - Budget impact analysis.

PMID- 28492785
TI  - Union Generates Success.

PMID- 28492786
TI  - The Brazilian Registry of Adult Patient Undergoing Cardiovascular Surgery, the
      BYPASS Project: Results of the First 1,722 Patients.
AB  - Objective: To report the early results of the BYPASS project - the Brazilian
      registrY of adult Patient undergoing cArdiovaScular Surgery - a national,
      observational, prospective, and longitudinal follow-up registry, aiming to chart
      a profile of patients undergoing cardiovascular surgery in Brazil, assessing the
      data harvested from the initial 1,722 patients. Methods: Data collection involved
      institutions throughout the whole country, comprising 17 centers in 4 regions:
      Southeast (8), Northeast (5), South (3), and Center-West (1). The study
      population consists of patients over 18 years of age, and the types of operations
      recorded were: coronary artery bypass graft (CABG), mitral valve, aortic valve
      (either conventional or transcatheter), surgical correction of atrial
      fibrillation, cardiac transplantation, mechanical circulatory support and
      congenital heart diseases in adults. Results: 83.1% of patients came from the
      public health system (SUS), 9.6% from the supplemental (private insurance)
      healthcare systems; and 7.3% from private (out-of -pocket) clinic. Male patients
      comprised 66%, 30% were diabetics, 46% had dyslipidemia, 28% previously sustained
      a myocardial infarction, and 9.4% underwent prior cardiovascular surgery.
      Patients underwent coronary artery bypass surgery were 54.1% and 31.5% to valve
      surgery, either isolated or combined. The overall postoperative mortality up to
      the 7th postoperative day was 4%; for CABG was 2.6%, and for valve operations,
      4.4%. Conclusion: This first report outlines the consecution of the Brazilian
      surgical cardiac database, intended to serve primarily as a tool for providing
      information for clinical improvement and patient safety and constitute a basis
      for production of research protocols.

PMID- 28492787
TI  - Validation of German Aortic Valve Score in a Multi-Surgeon Single Center.
AB  - OBJECTIVE:: Risk assessment for operative mortality is mandatory for all cardiac
      operations. For some operation types such as aortic valve repair, EuroSCORE II
      overestimates the mortality rate and a new scoring system (German AV score) has
      been developed for a more accurate assessment of operative risk. In this study,
      we aimed to validate German Aortic Valve Score in our clinic in patients
      undergoing isolated aortic valve replacement. METHODS:: A total of 35 patients
      who underwent isolated open aortic valve replacement between 2010 and 2013 were
      included. Patients with concomitant procedures and transcatheter aortic valve
      implantation were excluded. Patients' data were collected and analyzed
      retrospectively. Patients' risk scores EuroSCORE II were calculated online
      according to criteria described by EuroSCORE taskforce, Aortic Valve Scores were
      also calculated. RESULTS:: The mean age of patients was 61.14+/-13.25 years
      (range 29-80 years). The number of female patients was 14 (40%) and body mass
      index of 25 (71.43%) patients was in range of 22-35. Mean German Aortic Valve
      Score was 1.05+/-0.96 (min: 0 max: 4.98) and mean EuroSCORE was 2.30+/-2.60 (min:
      0.62, max: 2.30). The Aortic Valve Score scale showed better discriminative
      capacity (AUC 0.647, 95% CI 0.439-0.854). The goodness of fit was x2HL=16.63;
      P=0.436). EuroSCORE II scale had shown less discriminative capacity (AUC 0.397,
      95% CI 0.200-0.597). The goodness of fit was good for both scales. The goodness
      of fit was x2HL=30.10; P=0.610. CONCLUSION:: In conclusion, German AV score
      applies to our population with high predictive accuracy and goodness of fit.

PMID- 28492788
TI  - Hemoglobin A1c Levels Predicts Acute Kidney Injury after Coronary Artery Bypass
      Surgery in Non-Diabetic Patients.
AB  - INTRODUCTION:: Elevated hemoglobin A1c levels in patients with diabetes mellitus
      have been known as a risk factor for acute kidney injury after coronary artery
      bypass grafting. However, the relationship between hemoglobin A1c levels in non
      diabetics and acute kidney injury is under debate. We aimed to investigate the
      association of preoperative hemoglobin A1c levels with acute kidney injury in non
      diabetic patients undergoing isolated coronary artery bypass grafting. METHODS::
      202 non-diabetic patients with normal renal function (serum creatinine <1.4
      mg/dl) who underwent isolated coronary bypass were analyzed. Hemoglobin A1c level
      was measured at the baseline examination. Patients were separated into two groups
      according to preoperative Hemoglobin A1c level. Group 1 consisted of patients
      with preoperative HbA1c levels of < 5.6% and Group 2 consisted of patients with
      preoperative HbA1c levels of >= 5.6%. Acute kidney injury diagnosis was made by
      comparing baseline and postoperative serum creatinine to determine the presence
      of predefined significant change based on the Kidney Disease Improving Global
      Outcomes (KDIGO) definition. RESULTS:: Acute kidney injury occurred in 19 (10.5%)
      patients after surgery. The incidence of acute kidney injury was 3.6% in Group 1
      and 16.7% in Group 2. Elevated baseline hemoglobin A1c level was found to be
      associated with acute kidney injury (P=0.0001). None of the patients became
      hemodialysis dependent. The cut off value for acute kidney injury in our group of
      patients was 5.75%. CONCLUSION:: Our findings suggest that, in non-diabetics,
      elevated preoperative hemoglobin A1c level may be associated with acute kidney
      injury in patients undergoing coronary artery bypass grafting. Prospective
      randomized studies in larger groups are needed to confirm these results.

PMID- 28492789
TI  - Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement
      Patients.
AB  - OBJECTIVE:: Myocardial protection is the most important in cardiac surgery. We
      compared our modified single-dose long-acting lignocaine-based blood cardioplegia
      with short-acting St Thomas 1 blood cardioplegia in patients undergoing single
      valve replacement. METHODS:: A total of 110 patients who underwent single (aortic
      or mitral) valve replacement surgery were enrolled. Patients were divided in two
      groups based on the cardioplegia solution used. In group 1 (56 patients), long
      acting lignocaine based-blood cardioplegia solution was administered as a single
      dose while in group 2 (54 patients), standard St Thomas IB (short-acting blood
      based cardioplegia solution) was administered and repeated every 20 minutes. All
      the patients were compared for preoperative baseline parameters, intraoperative
      and all the postoperative parameters. RESULTS:: We did not find any statistically
      significant difference in preoperative baseline parameters. Cardiopulmonary
      bypass time were 73.8+/-16.5 and 76.4+/-16.9 minutes (P=0.43) and cross clamp
      time were 58.9+/-10.3 and 66.3+/-11.2 minutes (P=0.23) in group 1 and group 2,
      respectively. Mean of maximum inotrope score was 6.3+/-2.52 and 6.1+/-2.13
      (P=0.65) in group 1 and group 2, respectively. We also did not find any
      statistically significant difference in creatine-phosphokinase-MB (CPK-MB),
      Troponin-I levels, lactate level and cardiac functions postoperatively.
      CONCLUSION:: This study proves the safety and efficacy of long-acting lignocaine
      based single-dose blood cardioplegia compared to the standard short-acting multi
      dose blood cardioplegia in patients requiring the single valve replacement.
      Further studies need to be undertaken to establish this non-inferiority in
      situations of complex cardiac procedures especially in compromised patients.

PMID- 28492791
TI  - Respiratory Muscle Training Improves Diaphragm Citrate Synthase Activity and
      Hemodynamic Function in Rats with Heart Failure.
AB  - INTRODUCTION:: Enhanced respiratory muscle strength in patients with heart
      failure positively alters the clinical trajectory of heart failure. In an
      experimental model, respiratory muscle training in rats with heart failure has
      been shown to improve cardiopulmonary function through mechanisms yet to be
      entirely elucidated. OBJECTIVE:: The present report aimed to evaluate the
      respiratory muscle training effects in diaphragm citrate synthase activity and
      hemodynamic function in rats with heart failure. METHODS:: Wistar rats were
      divided into four experimental groups: sedentary sham (Sed-Sham, n=8), trained
      sham (RMT-Sham, n=8), sedentary heart failure (Sed-HF, n=7) and trained heart
      failure (RMT-HF, n=7). The animals were submitted to a RMT protocol performed 30
      minutes a day, 5 days/week, for 6 weeks. RESULTS:: In rats with heart failure,
      respiratory muscle training decreased pulmonary congestion and right ventricular
      hypertrophy. Deleterious alterations in left ventricular pressures, as well as
      left ventricular contractility and relaxation, were assuaged by respiratory
      muscle training in heart failure rats. Citrate synthase activity, which was
      significantly reduced in heart failure rats, was preserved by respiratory muscle
      training. Additionally, a negative correlation was found between citrate synthase
      and left ventricular end diastolic pressure and positive correlation was found
      between citrate synthase and left ventricular systolic pressure. CONCLUSION::
      Respiratory muscle training produces beneficial adaptations in the diaphragmatic
      musculature, which is linked to improvements in left ventricular hemodynamics and
      blood pressure in heart failure rats. The RMT-induced improvements in cardiac
      architecture and the oxidative capacity of the diaphragm may improve the clinical
      trajectory of patients with heart failure.

PMID- 28492790
TI  - Effects of Low-Dose Recombinant Human Brain Natriuretic Peptide on Anterior
      Myocardial Infarction Complicated by Cardiogenic Shock.
AB  - INTRODUCTION:: The mortality due to cardiogenic shock complicating acute
      myocardial infarction (AMI) is high even in patients with early
      revascularization. Infusion of low dose recombinant human brain natriuretic
      peptide (rhBNP) at the time of AMI is well tolerated and could improve cardiac
      function. OBJECTIVE:: The objective of this study was to evaluate the hemodynamic
      effects of rhBNP in AMI patients revascularized by emergency percutaneous
      coronary intervention (PCI) who developed cardiogenic shock. METHODS:: A total of
      48 patients with acute ST segment elevation myocardial infarction (STEMI)
      complicated by cardiogenic shock and whose hemodynamic status was improved
      following emergency PCI were enrolled. Patients were randomly assigned to rhBNP
      (n=25) and control (n=23) groups. In addition to standard therapy, study group
      individuals received rhBNP by continuous infusion at 0.005 ug kg-1 min-1 for 72
      hours. RESULTS:: Baseline characteristics, medications, and peak of cardiac
      troponin I (cTnI) were similar between both groups. rhBNP treatment resulted in
      consistently improved pulmonary capillary wedge pressure (PCWP) compared to the
      control group. Respectively, 7 and 9 patients died in experimental and control
      groups. No drug-related serious adverse events occurred in either group.
      CONCLUSION:: When added to standard care in stable patients with cardiogenic
      shock complicating anterior STEMI, low dose rhBNP improves PCWP and is well
      tolerated.

PMID- 28492792
TI  - Cervical Cannulation for Surgical Repair of Congenital Cardiac Defects in Infants
      and Small Children.
AB  - INTRODUCTION:: The biggest challenge faced in minimally invasive pediatric
      cardiac surgery is cannulation for cardiopulmonary bypass. Our technique and
      experience of cervical cannulation in infants and small children for repair of
      congenital cardiac defects is reported in this study. METHODS:: From January 2013
      to June 2015, 37 children (22 males) with mean age of 17.97+/-8.63 months and
      weight of 8.06+/-1.59 kg were operated on for congenital cardiac defects through
      right lateral thoracotomy. The most common diagnosis was ventricular septal
      defect (18 patients). In all patients, right common carotid artery, right
      internal jugular vein and inferior vena cava were cannulated for institution of
      cardiopulmonary bypass and aorta was cross clamped through right 2nd intercostal
      space. RESULTS:: There were no deaths or any major complications related to
      cervical cannulation. Common carotid artery cannulation provided adequate
      arterial inflow while internal jugular vein with inferior vena cava provided
      adequate venous return in all patients. No patient required conversion to
      sternotomy or developed vascular, neurological or wound related complications.
      Three patients had residual lesions (small leak across ventricular septal defect
      patch-2, Grade II left atrio-ventricular valve regurgitation-1) and one patient
      had mild left ventricular dysfunction. At discharge, both common carotid artery
      and internal jugular vein were patent on color Doppler ultrasonography in all
      patients. In a mean follow-up period of 11.4+/-2.85 months, all patients were
      doing well. No patient had any wound related, neurological or vascular
      complication. No patient had residual leak across ventricular septal defect
      patch. CONCLUSION:: Cervical cannulation of common carotid artery and internal
      jugular vein is a safe, reliable, efficient and quick method for institution of
      cardiopulmonary bypass in minimally invasive pediatric cardiac surgery.

PMID- 28492793
TI  - Left Atrial Ganglionated Plexi Detection is Related to Heart Rate and Early
      Recurrence of Atrial Fibrillation after Surgical Ablation.
AB  - INTRODUCTION:: Left atrial ganglionated plexi ablation is an adjuvant technique
      used to increase the success rate of surgical ablation of atrial fibrillation.
      Ganglionated plexi ablation requires previous detection. We aimed to assess
      determinants of successful ganglionated plexi detection and to correlate range of
      ganglionated plexi ablation with risk of early atrial fibrillation recurrence.
      METHODS:: The study involved 34 consecutive patients referred for surgical
      coronary revascularization with concomitant atrial fibrillation ablation.
      Ganglionated plexi detection was done by inducing vagal reflexes in the area of
      the pulmonary veins and left atrial fat pads. RESULTS:: Detection of GP was
      successful in 85% of the patients. There was no difference in preoperative
      characteristics nor in atrial fibrillation type between patients in whom
      ganglionated plexi detection was successful and others. The number of detected
      ganglionated plexi correlated significantly only with preoperative resting heart
      rate. Significant negative correlation was found in patients with preoperative
      heart rate>75 beat/min in terms of total number of detected ganglionated plexi
      (P=0.04). Average number of detected ganglionated plexi was significantly higher
      in patients with in-hospital atrial fibrillation recurrence requiring electrical
      cardioversion (3.8+/-3) in comparison to rest of the study population (2+/-1.3;
      P=0.02). In patients in whom 4 or more ganglionated plexi were detected,
      significantly increased risk of in-hospital atrial fibrillation recurrence was
      observed (OR 15; 95% CI 1.5-164; P=0.003). CONCLUSION:: Left atrial ganglionated
      plexi detection was unsuccessful in a considerable percentage of patients.
      Preoperative heart rate significantly influenced positive ganglionated plexi
      detection and number of ablated ganglia. Higher number of detected ganglionated
      plexi was related with early recurrence of atrial fibrillation.

PMID- 28492795
TI  - Anterior Spinal Artery Syndrome Following Coronary Artery Bypass Grafting: a Case
      Report.
AB  - We present a patient with unstable angina candidate for coronary artery bypass
      grafting. Saphenous vein graft was used in obtuse marginal and left internal
      mammary artery to left anterior descending artery properly. After surgery, the
      patient experienced flaccid paralysis of lower limb and impaired sensation of
      touch and warmth of knee and below. A computed tomography angiogram of lower
      limbs and thoracolumbar magnetic resonance imaging showed no abnormality. Based
      on the symptom, clinical diagnosis of anterior spinal artery syndrome was
      considered. The artery of Adamkiewicz is an important supplier to the anterior
      spinal artery. Internal thoracic mammary artery, used in coronary artery bypass
      grafting, is suspected as a collateral supplier of the artery of Adamkiewicz and
      has been accused for cause of spinal infarction.

PMID- 28492794
TI  - Exploring Vascular Function Biomarkers: Implications for Rehabilitation.
AB  - The endothelium plays an important role in maintaining vascular homeostasis and
      regulating blood vessel function. Endothelial function is considered an
      independent predictor for risk of future cardiovascular events in cardiovascular
      and non-cardiovascular patients, as well as a predictor for postoperative
      complications in cardiovascular surgery patients. Brachial artery flow-mediated
      dilation by high-resolution ultrasound is widely used to evaluate endothelium
      dependent vasodilation, which is mainly mediated by nitric oxide release.
      Physical exercise exerts beneficial effects on endothelial function and can be
      used in both primary and secondary prevention of cardiac and peripheral artery
      diseases, even in the postoperative period of cardiovascular surgery.

PMID- 28492796
TI  - A Concomitant Intramyocardial and Pulmonary Hydatid Cyst: A Rare Case Report.
AB  - Cardiac hydatid cyst is an uncommon but potentially fatal disease. In cystic
      Echinococcus humans are an accidental host. Liver and lungs are the most
      frequently involved organs. Herein a unique case of intramyocardial hydatid cyst
      of left ventricle along with pulmonary hydatid cyst in a 38-year-old lady is
      reported. Surgical removal of the cardiac hydatid cyst was done with the aid of
      cardiopulmonary bypass followed by removal of pulmonary hydatid cyst.

PMID- 28492797
TI  - Let's Talk about Moving: The Impact of Cardiorespiratory Fitness, Exercise, Steps
      and Sitting on Cardiovascular Risk.

PMID- 28492798
TI  - Medicinal plants profile used by the 3rd District population of Maceio-AL.
AB  - Herein the use of medicinal plants by the population of the 3rd Sanitary District
      of Maceio-AL city is reported. Transversal description was conducted from
      February 2013 to January 2014, with a sample of 116 individuals of both Gender
      Genders aged over 18 years. The ethnobotanical information interviews
      ethnobotanical information were obtained through semi - structured questionnaire
      featuring the use of medicinal plants and social and economical data. Descriptive
      statistics was applied for quantitative variables as mean and standard deviation
      and proportions for qualitative variables in the frequency table format. The
      results showed that 85.34% of the interviewees used plants for medicinal
      purposes. As the majority of these were (73.28%) females in the age group between
      30-60 years of old. Among a total of 45 identified plant species, the highest use
      frequency were for Boldus Peumus (bilberry), Melissa officinalis (lemon balm),
      and Mentha piperita (mint). The most widely used plant foliage part was (53.53%)
      prepared as an infusion (55.5%). The use of medicinal plants in Maceio cityis
      widespread, highlighting the importance of ethnobotanical knowledge for the study
      of medicinal plants.

PMID- 28492799
TI  - Reproductive biology of endemic Solanum melissarum Bohs (Solanaceae) and updating
      of its current geographic distribution as the basis for its conservation in the
      Brazilian Cerrado.
AB  - The genus Solanum (family Solanaceae) includes more than 1400 species and has
      buzz-pollinated flowers with poricidal anthers. The present study aimed to
      describe the distribution, breeding system and pollination mechanism of Solanum
      melissarum, a species endemic to Brazil. The study of breeding system was
      conducted in an urban forest fragment in Jatai, GO. Distribution data were
      gathered from floristic surveys and digital plant databases. The floral
      morphology and the pollination mechanism were studied on through field
      observations and preserved flowers. The breeding system was determined through
      hand pollination treatments. The species has a distribution only in the Brazilian
      Atlantic forest coastal, and this study provides the first records of S.
      melissarum for the state of Goias. The pendulous flowers have poricidal anthers
      close to the stigma, with membranous thecae joined by a connective bearing
      osmophores that attract males of Euglossa cordata bees. As they collect
      fragrances, the bees press the thecae and pollen is released through a bellows
      mechanism. Based on the hand-pollination treatments, this species is self
      incompatible. Isolated forest fragments may not include enough pollinators to
      ensure the pollination of plants with specialized systems. However, they are
      essential for the conservation of species with interesting phytogeographic
      patterns, such as the vicariance observed in S. melissarum, and for the
      conservation of regional diversity.

PMID- 28492800
TI  - Fungal infection control by garlic extracts (Allium sativum L.) and modulation of
      peritoneal macrophages activity in murine model of sporotrichosis.
AB  - Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal
      vegetable since 3,000 BC. Allicin is the main component of garlic, being
      attributed to it the most of its biological activities, such as bactericidal,
      antifungal and antiviral actions. However, other compounds of garlic present
      antioxidant, hypocholesterolemic, vasodilator activities, protective action
      against different types of cancer, and immunomodulatory. Fungal infections are
      important causes of morbidity and mortality in people mainly in immunosuppressed
      ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common
      subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life
      in soil or plants, infecting people and animals mainly through skin injuries and
      bruises. The main of this work was to evaluate the influence of garlic consuming
      on immune modulation of healthy and infected Swiss mice in induced way by S.
      schenckii, since these animals functioning of peritoneal macrophages as well as
      the nitric oxide and cytokines' production (IL-1beta, IL-10 and IL-12) and to
      evaluate the antifungal potential of garlic with S. schenckii through minimum
      inhibitory concentration test and colony-forming units. The results showed that
      garlic offers antifungal potential with S. schenckii. The oral taking of garlic
      extracts influences the releasing of cytokines by macrophages, regular consuming
      shows anti-inflammatory effect, and its acute use may take to an inflammatory
      response. Mice that consumed garlic responded more effectively to fight against
      the infection.

PMID- 28492801
TI  - Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in
      breast cancer.
AB  - OBJECTIVES: Calcitriol antiproliferative effects were observed in xenografts of
      breast cancer cell lines, however they were not yet investigated in tumorgrafts,
      consisting of freshly collected breast cancer samples xenografted into animals.
      To establish a tumorgraft model, from freshly collected breast cancer samples,
      which were directly implanted in nude mice, to study calcitriol effects. METHODS:
      Breast cancer samples collected from 12 patients were orthotopically implanted
      into nude mice. Animals were treated with weekly intratumoral injections of
      calcitriol 3 MUg/Kg, which was previously shown to induce peak serum calcitriol
      levels in the predicted therapeutic range. RESULTS: Success engraftment rate was
      25%. Tumorgrafts were established from aggressive (HER2 positive or histological
      grade 3) highly proliferative samples and original tumor characteristics were
      preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that
      the genomic vitamin D pathway is active in tumorgrafts. However, no differences
      in the expression of proliferation and apoptosis markers (BrdU incorporation,
      Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly
      proliferative tumor samples. CONCLUSIONS: Tumorgrafts seem a promising model to
      explore other calcitriol doses and regimens, considering the heterogeneity of the
      disease and microenvironment interactions.

PMID- 28492802
TI  - Gonadotrophic, prolactin, corticosterone, and gonadal hormones levels over 15
      months in Giant Amazon River Turtles - Podocnemis expansa (Schweigger, 1812)
      (Testudines: Podocnemididae), in captive conditions.
AB  - In order to achieve successful captive breeding the Podocnemis expansa, it is
      necessary to study their reproductive endocrinology. The purpose of this research
      was to evaluate and characterize plasma concentrations in gonadotrophic, gonadic,
      corticosterone and prolactin hormones from Giant Amazon Turtles under captive
      conditions. Blood samples were collected over a 15 month period. The samples were
      assayed by the use of radioimmunoassay, prolactin, corticosterone, LH, FSH,
      testosterone, 17beta-estradiol and progesterone. We verified significant seasonal
      pattern increase in 17beta-estradiol levels and decrease in progesterone levels
      in the course of a year, which indicates vitellogenesis. This is related to
      normal ovarian cycles and possibly to the functional integrity of the
      hypothalamus-pituitary-gonad axis of captive females. There were negative
      correlations between testosterone and corticosterone in the male samples,
      suggestive of stress (management stress) on the reproductive system. The plasma
      concentrations of gonadotrophic, gonadic, prolactin and corticosterone hormones
      may be used as a reference for further research and possible therapeutic
      approaches. The data collected during this research are unprecedented for this
      species and may serve as a reference for future research regarding the
      reproductive cycle of this turtle, also allowing reproductive management while in
      captivity. Information about these hormones must be gathered from wild
      populations during different periods of the year for better clarification of the
      reproductive physiology of this species.

PMID- 28492803
TI  - Tropical forages: morphoanatomy of plants grown in areas with the death of
      pasture syndrome.
AB  - Roots and leaves of Panicum maximum Tanzania, Mombaca and Massai; Urochloa
      brizantha Piata, Marandu and Xaraes; Urochloa humidicola Llanero; Urochloa
      ruziziensis Ruzizienses; Urochloa hybrida Mulato II and Cynodon nlemfuensis
      Estrela-roxa were analyzed, seeking to identify characters for better adaptation
      to the environment that may interfere with digestibility of tissue from the point
      of view of the rumen in cattle. Were planted ten cultivars in a completely
      randomized blocks with three repetitions. Was collected vegetative material,
      which histological slides were prepared from middle third of the sections of
      roots and leaves. Were observed differences (p>0.05) in the roots: higher volume
      of epidermal cells (28.62 um) and overall diameter (1926.41 um) of Llanero;
      thicker vascular cylinder (975.09 um) and more protoxylem (42.25) in Estrela-roxa
      and occurrence of aerenchyma in cultivars Piata, Mulato II, Xaraes, Massai,
      Llanero and Estrela-roxa; Were found higher proportions of bulliform cells in the
      leaves (121.07 um) and thicker leaf mesophyll in U. humidicola Llanero (263.63
      um); higher proportion of sclerenchyma fibers in Xaraes and Marandu; lower
      results for amount of fibers in P. maximum Massai. We conclude that the cultivars
      Estrela-roxa, Llanero and Massai have greater adaptability to the environment and
      better nutritional quality.

PMID- 28492804
TI  - Post-fire reproduction of herbs at a savanna-gallery forest boundary in Distrito
      Federal, Brazil.
AB  - In Cerrado, studies of post-fire vegetation recovery show that some herbaceous
      species are able to flower shortly after fires. However, these were mainly short
      term studies that focused on grasslands and savannas. Little is known about the
      effects of fire on ground layer of forests that border the savannas in Central
      Brazil. Thus, an accidental burning gave us the opportunity to describe the
      reproductive activity of the ground layer vegetation after a fire event along a
      savanna-forest boundary at the IBGE Ecological Reserve, Brasilia, Brazil. During
      the 16-month of the inventory, we registered 170 herbaceous species flowering or
      fruiting, of which 52 species (31%) may have been influenced by fire that changed
      their times of reproduction. In the savanna plots reproduction peaked at the end
      of the rainy season. Of the total number of reproducing species, 90 species
      occurred only in the savanna and four in the forest. Five herbs were recorded in
      the forest, savanna and border environments. Late dry season fire probably lead
      the majority of herbaceous species to have their reproduction spread throughout
      the study time.

PMID- 28492806
TI  - Plankton crustaceans in bays with different trophic status in Llanquihue lake (41
      degrees  S Chile).
AB  - The Llanquihue lake is included in the called Araucanian or Nord Patagonian lakes
      located between 38-41 degrees  S. These lakes are characterized by their oligo
      mesotrophic status due to human intervention which takes to the increase in
      nutrients inputs from industries and towns. Effects on zooplankton assemblages
      are observed with marked increase of daphnids abundance. The aim of the present
      study is to analyze the trophic status and zooplankton relative abundance in
      different bays of Llanquihue lake. It was found direct associations between
      chlorophyll a with daphnids percentage, total dissolved nitrogen with reactive
      soluble phosphorus nitrogen/phosphorus molar radio with cyclopoids percentage,
      and an inverse relation between daphnids and calanoids percentages. The
      occurrence of three kinds of microcrustacean assemblages and environmental
      conditions was evidenced: the first one with high calanoids percentage, low
      species number and low chlorophyll and nutrients concentration, a second with
      moderate chlorophyll and nutrients concentration and moderate daphnids
      percentage; high species number and a third site with high chlorophyll and
      nutrients concentration, high daphnids percentage and high species number.
      Daphnids increase under mesotrophic status, agree with similar results observed
      for southern Argentinean and New Zealand lakes.

PMID- 28492807
TI  - Biochemical parameters of silver catfish (Rhamdia quelen) after transport with
      eugenol or essential oil of Lippia alba added to the water.
AB  - The transport of live fish is a routine practice in aquaculture and constitutes a
      considerable source of stress to the animals. The addition of anesthetic to the
      water used for fish transport can prevent or mitigate the deleterious effects of
      transport stress. This study investigated the effects of the addition of eugenol
      (EUG) (1.5 or 3.0 uL L-1) and essential oil of Lippia alba (EOL) (10 or 20 uL L
      1) on metabolic parameters (glycogen, lactate and total protein levels) in liver
      and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the
      levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS)
      and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in
      the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported
      for four hours in plastic bags (loading density of 169.2 g L-1). The addition of
      various concentrations of EUG (1.5 or 3.0 uL L-1) and EOL (10 or 20 uL L-1) to
      the transport water is advisable for the transportation of silver catfish, since
      both concentrations of these substances increased the levels of NPSH antioxidant
      and decreased the TBARS levels in the liver. In addition, the lower liver levels
      of glycogen and lactate in these groups and lower AChE activity in the brain (EOL
      10 or 20 uL L-1) compared to the control group indicate that the energetic
      metabolism and neurotransmission were lower after administration of anesthetics,
      contributing to the maintenance of homeostasis and sedation status.

PMID- 28492808
TI  - FAMLF is a target of miR-181b in Burkitt lymphoma.
AB  - Burkitt lymphoma (BL) is a highly malignant non-Hodgkin's lymphoma that is
      closely related to the abnormal expression of genes. Familial acute myelogenous
      leukemia related factor (FAMLF; GenBank accession No. EF413001.1) is a novel gene
      that was cloned by our research group, and miR-181b is located in the intron of
      the FAMLF gene. To verify the role of miR-181b and FAMLF in BL, RNAhybrid
      software was used to predict target site of miR-181b on FAMLF and real-time
      quantitative PCR (RQ-PCR) was used to detect expression of miR-181b and FAMLF in
      BL patients, Raji cells and unaffected individuals. miR-181b was then transfected
      into Raji and CA46 cell lines and FAMLF expression was examined by RQ-PCR and
      western blotting. Further, Raji cells viability and proliferation were detected
      by MTT and clone formation, and Raji cell cycle and apoptosis were detected by
      flow cytometry. The results showed that miR-181b can bind to bases 21-42 of the
      FAMLF 5' untranslated region (UTR), FAMLF was highly expressed and miR-181b was
      lowly expressed in BL patients compared with unaffected individuals. FAMLF
      expression was significantly and inversely correlated to miR-181b expression, and
      miR-181b negatively regulated FAMLF at posttranscriptional and translational
      levels. A dual-luciferase reporter gene assay identified that the 5' UTR of FAMLF
      mRNA contained putative binding sites for miR-181b. Down-regulation of FAMLF by
      miR-181b arrested cell cycle, inhibited cell viability and proliferation in a BL
      cell line model. Our findings explain a new mechanism of BL pathogenesis and may
      also have implications in the therapy of FAMLF-overexpressing BL.

PMID- 28492811
TI  - Permanent education in primary health care: perception of local health managers.
AB  - Objectives: To know the health education strategies advocated and developed for
      workers of primary care, in the view of managers. Method: The study is
      characterized as a qualitative, descriptive and exploratory research. A
      semistructured interview was used to collect data. The sample population was
      chosen intentionally, with an audience of 26 municipal health managers ascribed
      to a regional health coordination office, located in the north/northwest of the
      Rio Grande do Sul State. Results: The thematic analysis allowed the construction
      of two empirical categories: educational strategies, compartmentalized,
      discontinuous and with technicist bases; and the insipience/absence of
      educational proposals. Final considerations: The results show a reality that
      needs to be transformed by all people involved in health work process: teachers
      and students, users, members of health councils, workers and managers.
      Realistically, there is a quest for change in services, to qualify the
      comprehensiveness of health care.

PMID- 28492810
TI  - Rimonabant improves metabolic parameters partially attributed to restoration of
      high voltage-activated Ca2+ channels in skeletal muscle in HFD-fed mice.
AB  - Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising
      strategies for the treatment of obesity and other related metabolic disorders.
      Although CB1R inhibition may cause adverse psychiatric effects including
      depression and anxiety, the investigation of the role of peripheral CB1R on
      weight loss and related metabolic parameters are urgently needed. We first
      explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist,
      on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice.
      Then, real-time PCR and electrophysiology were used to explore the contribution
      of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on
      rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD
      feeding caused body weight gain, and decreased glucose/insulin tolerance in mice
      compared to those in the regular diet group (P<0.05), which was restored by
      rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs
      and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the
      control group. Daily treatment with rimonabant for 5 weeks was shown to counter
      such decrease (P<0.05). Collectively, our findings provided a novel understanding
      for peripheral CB1R's role in the modulation of body weight and glucose
      homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as
      potential targets for obesity treatment.

PMID- 28492809
TI  - Serum microRNA-30c levels are correlated with disease progression in Xinjiang
      Uygur patients with chronic hepatitis B.
AB  - We aimed to investigate the potential role and mechanism of microRNA-30c (miR
      30c) in the pathological development of chronic hepatitis B (CHB). The serum
      levels of miR-30c in hepatitis B virus (HBV) carrier Xinjiang Uygur patients with
      inactive, low-replicative, high-replicative and HBe antigen-positive CHB were
      investigated. HepG2 cells were co-transfected with pHBV1.3 and miR-30c mimic or
      inhibitor or scramble RNA. The effects of miR-30c dysregulation on HBV
      replication and gene expression, cell proliferation and cell cycle were then
      investigated. miR-30c was down-regulated in Xinjiang Uygur patients with CHB
      compared to healthy controls and its expression level discriminated HBV carrier
      patients with inactive, low-replicative, high-replicative and HBe antigen
      positive risk for disease progression. Overexpression of miR-30c significantly
      inhibited HBV replication and the expressions of HBV pgRNA, capsid-associated
      virus DNA and Hbx in hepatoma cells. Moreover, overexpression of miR-30c
      significantly inhibited cell proliferation and delayed G1/S phase transition in
      hepatoma cells. Opposite effects were obtained after suppression of miR-30c. Our
      results indicate that miR-30c was down-regulated in Xinjiang Uygur patients with
      CHB, and miR-30c levels could serve as a marker for risk stratification of HBV
      infection. Down-regulation of miR-30c may result in the progression of CHB via
      promoting HBV replication and cell proliferation.

PMID- 28492812
TI  - Palliative care in paediatric oncology in nursing education.
AB  - Objective: To identify and understand the view of students regarding palliative
      care in paediatric oncology during a graduate programme. Methods: Exploratory
      research with a qualitative approach conducted in a school of nursing in Rio de
      Janeiro. Data were collected from September to November 2014, through semi
      structured interviews with 20 students enrolled in the last period of a graduate
      programme. The data were subjected to thematic analysis. Results: The results
      produced two thematic units: the (un)preparedness of nursing students regarding
      palliative care in paediatric oncology and how the subject of palliative care in
      paediatric oncology is approached in the graduate programme. The students
      mentioned difficulties in providing this care and their lack of exposure to the
      topic during their graduate studies. They stated strategies to prepare for the
      provision of care, and talked about how the subject should be addressed in their
      curricular programme. Conclusion: It is necessary to expand discussions on
      palliative care in paediatric oncology during the nurses' graduate programme.

PMID- 28492813
TI  - Patient safety in the care of hospitalised children: evidence for paediatric
      nursing.
AB  - Objectives: To describe evidence of international literature on the safe care of
      the hospitalised child after the World Alliance for Patient Safety and list
      contributions of the general theoretical framework of patient safety for
      paediatric nursing. Method: An integrative literature review between 2004 and
      2015 using the databases PubMed, Cumulative Index of Nursing and Allied Health
      Literature (CINAHL), Scopus, Web of Science and Wiley Online Library, and the
      descriptors Safety or Patient safety, Hospitalised child, Paediatric nursing, and
      Nursing care. Results: Thirty-two articles were analysed, most of which were from
      North American, with a descriptive approach. The quality of the recorded
      information in the medical records, the use of checklists, and the training of
      health workers contribute to safe care in paediatric nursing and improve the
      medication process and partnerships with parents. Conclusion: General information
      available on patient safety should be incorporated in paediatric nursing care.

PMID- 28492814
TI  - Implementation of Rapid Treatment and Interfacility Transport for Patients With
      Suspected Stroke by Large-Vessel Occlusion: In One Door and Out the Other.

PMID- 28492815
TI  - Enhanced Surgical Recovery Through Enhanced Research From Integrated Health
      Systems.

PMID- 28492817
TI  - Different Pediatric Survival After Cardiac Arrest-Reply.

PMID- 28492816
TI  - Enhanced Recovery After Surgery Program Implementation in 2 Surgical Populations
      in an Integrated Health Care Delivery System.
AB  - Importance: Novel approaches to perioperative surgical care focus on optimizing
      nutrition, mobility, and pain management to minimize adverse events after
      surgical procedures. Objective: To evaluate the outcomes of an enhanced recovery
      after surgery (ERAS) program among 2 target populations: patients undergoing
      elective colorectal resection and patients undergoing emergency hip fracture
      repair. Design, Setting, and Participants: A pre-post difference-in-differences
      study before and after ERAS implementation in the target populations compared
      with contemporaneous surgical comparator groups (patients undergoing elective
      gastrointestinal surgery and emergency orthopedic surgery). Implementation began
      in February and March 2014 and concluded by the end of 2014 at 20 medical centers
      within the Kaiser Permanente Northern California integrated health care delivery
      system. Exposures: A multifaceted ERAS program designed with a particular focus
      on perioperative pain management, mobility, nutrition, and patient engagement.
      Main Outcomes and Measures: The primary outcome was hospital length of stay.
      Secondary outcomes included hospital mortality, home discharge, 30-day
      readmission rates, and complication rates. Results: The study included a total of
      3768 patients undergoing elective colorectal resection (mean [SD] age, 62.7
      [14.1] years; 1812 [48.1%] male) and 5002 patients undergoing emergency hip
      fracture repair (mean [SD] age, 79.5 [11.8] years; 1586 [31.7%] male). Comparator
      surgical patients included 5556 patients undergoing elective gastrointestinal
      surgery and 1523 patients undergoing emergency orthopedic surgery. Most process
      metrics had significantly greater changes in the ERAS target populations after
      implementation compared with comparator surgical populations, including those for
      ambulation, nutrition, and opioid use. Hospital length of stay and postoperative
      complication rates were also significantly lower among ERAS target populations
      after implementation. The rate ratios for postoperative complications were 0.68
      (95% CI, 0.46-0.99; P = .04) for patients undergoing colorectal resection and
      0.67 (95% CI, 0.45-0.99, P = .05) for patients with hip fracture. Among patients
      undergoing colorectal resection, ERAS implementation was associated with
      decreased rates of hospital mortality (0.17; 95% CI, 0.03-0.86; P = .03), whereas
      among patients with hip fracture, implementation was associated with increased
      rates of home discharge (1.24; 95% CI, 1.06-1.44; P = .007). Conclusions and
      Relevance: Multicenter implementation of an ERAS program among patients
      undergoing elective colorectal resection and patients undergoing emergency hip
      fracture repair successfully altered processes of care and was associated with
      significant absolute and relative decreases in hospital length of stay and
      postoperative complication rates. Rapid, large-scale implementation of a
      multidisciplinary ERAS program is feasible and effective in improving surgical
      outcomes.

PMID- 28492819
TI  - Inappropriate Comparator Group in Study of Selective Serotonin Reuptake
      Inhibitors and Risk for Intracranial Hemorrhage.

PMID- 28492818
TI  - Different Pediatric Survival After Cardiac Arrest.

PMID- 28492820
TI  - Missing Reference.

PMID- 28492821
TI  - Risk Associated With Complications and Mortality After Urgent Surgery vs Elective
      and Emergency Surgery: Implications for Defining "Quality" and Reporting Outcomes
      for Urgent Surgery.
AB  - Importance: Given the current climate of outcomes-driven quality reporting, it is
      critical to appropriately risk stratify patients using standardized metrics.
      Objective: To elucidate the risk associated with urgent surgery on complications
      and mortality after general surgical procedures. Design, Setting, and
      Participants: This retrospective review used the American College of Surgeons
      National Surgery Quality Improvement Program database to capture all general
      surgery cases performed at 435 hospitals nationwide between January 1, 2013, and
      December 31, 2013. Data analysis was performed from November 11, 2015, to
      February 16, 2017. Exposures: Any operations coded as both nonelective and
      nonemergency were designated into a novel category titled urgent. Main Outcomes
      and Measures: The primary outcome was 30-day mortality; secondary outcomes
      included 30-day rates of complications, reoperation, and readmission in urgent
      cases compared with both elective and emergency cases. Results: Of 173 643
      patients undergoing general surgery (101 632 females and 72 011 males), 130 235
      (75.0%) were categorized as elective, 22 592 (13.0%) as emergency, and 20 816
      (12.0%) as nonelective and nonemergency. When controlling for standard American
      College of Surgeons National Surgery Quality Improvement Program preoperative
      risk factors, with elective surgery as the reference value, the 3 groups had
      significantly distinct odds ratios (ORs) of experiencing any complication (urgent
      surgery: OR, 1.38; 95% CI, 1.30-1.45; P < .001; and emergency surgery: OR, 1.65;
      95% CI, 1.55-1.76; P < .001) and of mortality (urgent surgery: OR, 2.32; 95% CI,
      2.00-2.68; P < .001; and emergency surgery: OR, 2.91; 95% CI, 2.48-3.41; P <
      .001). Surgical procedures performed urgently had a 12.3% rate of morbidity (n =
      2560) and a 2.3% rate of mortality (n = 471). Conclusions and Relevance: This
      study highlights the need for improved risk stratification on the basis of
      urgency because operations performed urgently have distinct rates of morbidity
      and mortality compared with procedures performed either electively or emergently.
      Because we tie quality outcomes to reimbursement, such a category should improve
      predictive models and more accurately reflect the quality and value of care
      provided by surgeons who do not have traditional elective practices.

PMID- 28492822
TI  - Comparing Anti-Vascular Endothelial Growth Factor Therapies for Central Retinal
      Vein Occlusion.

PMID- 28492823
TI  - Assessment of the Focused Practice Improvement Module Pilot Program of the
      American Board of Dermatology for Meeting Requirements of Maintenance of
      Certification.

PMID- 28492825
TI  - Mohs Micrographic Surgery Use in the United States Based on Medicare Data.

PMID- 28492824
TI  - Perceived Discrimination Experienced by Physician Mothers and Desired Workplace
      Changes: A Cross-sectional Survey.

PMID- 28492826
TI  - Association of Cost Sharing With Use of Home Health Services Among Medicare
      Advantage Enrollees.
AB  - Importance: Several policy proposals advocate introducing copayments for home
      health care in the Medicare program. To our knowledge, no prior studies have
      assessed this cost-containment strategy. Objective: To determine the association
      of home health copayments with use of home health services. Design, Setting, and
      Participants: A difference-in-differences case-control study of 18 Medicare
      Advantage (MA) plans that introduced copayments for home health care between 2007
      and 2011 and 18 concurrent control MA plans. The study included 135 302 enrollees
      in plans that introduced copayment and 155 892 enrollees in matched control
      plans. Exposures: Introduction of copayments for home health care between 2007
      and 2011. Main Outcomes and Measures: Proportion of enrollees receiving home
      health care, annual numbers of home health episodes, and days receiving home
      health care. Results: Copayments for home health visits ranged from $5 to $20 per
      visit, which were estimated to be associated with $165 (interquartile range
      [IQR], $45-$180) to $660 (IQR, $180-$720) in out-of-pocket spending for the
      average user of home health care. The increased copayment for home health care
      was not associated with the proportion of enrollees receiving home health care
      (adjusted difference-in-differences, -0.15 percentage points; 95% CI, -0.38 to
      0.09), the number of home health episodes per user (adjusted difference-in
      differences, 0.01; 95% CI, -0.01 to 0.03), and home health days per user
      (adjusted difference-in-differences, -0.19; 95% CI, -3.02 to 2.64). In both
      intervention and control plans and across all levels of copayments, we observed
      higher disenrollment rates among enrollees with greater baseline use of home
      health care. Conclusions and Relevance: We found no evidence that imposing
      copayments reduced the use of home health services among older adults. More
      intensive use of home health services was associated with increased rates of
      disenrollment in MA plans. The findings raise questions about the potential
      effectiveness of this cost-containment strategy.

PMID- 28492828
TI  - Cost Sharing and Home Health Care.

PMID- 28492827
TI  - Mother's Day for Women in Medicine-Better Than Roses.

PMID- 28492831
TI  - Abrupt Onset of Pustules in a Child.

PMID- 28492829
TI  - Inequalities in Life Expectancy Among US Counties, 1980 to 2014: Temporal Trends
      and Key Drivers.
AB  - Importance: Examining life expectancy by county allows for tracking geographic
      disparities over time and assessing factors related to these disparities. This
      information is potentially useful for policy makers, clinicians, and researchers
      seeking to reduce disparities and increase longevity. Objective: To estimate
      annual life tables by county from 1980 to 2014; describe trends in geographic
      inequalities in life expectancy and age-specific risk of death; and assess the
      proportion of variation in life expectancy explained by variation in
      socioeconomic and race/ethnicity factors, behavioral and metabolic risk factors,
      and health care factors. Design, Setting, and Participants: Annual county-level
      life tables were constructed using small area estimation methods from
      deidentified death records from the National Center for Health Statistics (NCHS),
      and population counts from the US Census Bureau, NCHS, and the Human Mortality
      Database. Measures of geographic inequality in life expectancy and age-specific
      mortality risk were calculated. Principal component analysis and ordinary least
      squares regression were used to examine the county-level association between life
      expectancy and socioeconomic and race/ethnicity factors, behavioral and metabolic
      risk factors, and health care factors. Exposures: County of residence. Main
      Outcomes and Measures: Life expectancy at birth and age-specific mortality risk.
      Results: Counties were combined as needed to create stable units of analysis over
      the period 1980 to 2014, reducing the number of areas analyzed from 3142 to 3110.
      In 2014, life expectancy at birth for both sexes combined was 79.1 (95%
      uncertainty interval [UI], 79.0-79.1) years overall, but differed by 20.1 (95%
      UI, 19.1-21.3) years between the counties with the lowest and highest life
      expectancy. Absolute geographic inequality in life expectancy increased between
      1980 and 2014. Over the same period, absolute geographic inequality in the risk
      of death decreased among children and adolescents, but increased among older
      adults. Socioeconomic and race/ethnicity factors, behavioral and metabolic risk
      factors, and health care factors explained 60%, 74%, and 27% of county-level
      variation in life expectancy, respectively. Combined, these factors explained 74%
      of this variation. Most of the association between socioeconomic and
      race/ethnicity factors and life expectancy was mediated through behavioral and
      metabolic risk factors. Conclusions and Relevance: Geographic disparities in life
      expectancy among US counties are large and increasing. Much of the variation in
      life expectancy among counties can be explained by a combination of socioeconomic
      and race/ethnicity factors, behavioral and metabolic risk factors, and health
      care factors. Policy action targeting socioeconomic factors and behavioral and
      metabolic risk factors may help reverse the trend of increasing disparities in
      life expectancy in the United States.

PMID- 28492832
TI  - Dementia Care, Women's Health, and Gender Equity: The Value of Well-Timed
      Caregiver Support.

PMID- 28492830
TI  - Changes in Psychosocial Measures After a 6-Week Field Trial.
AB  - Purpose: The purpose of this study was to assess the extent to which intervention
      with hearing aids, namely, a 6-week hearing aid field trial, can minimize the
      psychosocial consequences of hearing loss in adults who have previously not
      sought treatment for their hearing loss. Method: Twenty-four adults with mild to
      moderate bilateral sensorineural hearing loss, who had never worn hearing aids or
      sought help for their hearing loss, participated in this study. Participants were
      fitted with receiver-in-canal hearing aids, bilaterally, and wore them for 6
      weeks. Participants completed subjective measures of hearing handicap and
      attitudes about hearing loss and hearing aids before, during, and after the
      hearing aid trial. A control group of age-matched participants followed the same
      experimental protocol, except they were not fitted with hearing aids. Results:
      Using hearing aids for 6 weeks significantly reduced participants' perceived
      stigma of hearing aids, personal distress and inadequacy due to hearing
      difficulties, and hearing handicap. Conclusions: A hearing aid trial can have a
      positive effect on a person's attitudes toward wearing hearing aids and decrease
      hearing handicap.

PMID- 28492833
TI  - Treatment of Low Bone Density or Osteoporosis to Prevent Fracture.

PMID- 28492835
TI  - Incorrect Description of Patient Compensation in Methods Section.

PMID- 28492837
TI  - Topical Mercurials for the Treatment of Pediculosis.

PMID- 28492834
TI  - Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial
      Cell Death.
AB  - Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact
      on vocal function. This review article provides an overview of apoptosis, the
      most commonly studied type of programmed cell death. Because apoptosis can damage
      epithelial cells, this article examines the implications of apoptosis on diseases
      affecting the vocal fold cover. Method: A review of the extant literature was
      performed. We summarized the topics of epithelial tissue properties and apoptotic
      cell death, described what is currently understood about apoptosis in the vocal
      fold, and proposed several possible explanations for how the role of abnormal
      apoptosis during wound healing may be involved in vocal pathology. Results and
      Conclusions: Apoptosis plays an important role in maintaining normal epithelial
      tissue function. The biological mechanisms responsible for vocal fold diseases of
      epithelial origin are only beginning to emerge. This article discusses
      speculations to explain the potential role of deficient versus excessive rates of
      apoptosis and how disorganized apoptosis may contribute to the development of
      common diseases of the vocal folds.

PMID- 28492838
TI  - Revisiting the History and Importance of Phototherapy in Dermatology.

PMID- 28492839
TI  - Of Wine Stains and Vases-William Allen Sturge's Diverse Legacy.

PMID- 28492840
TI  - Al Rhazes and the Beginning of the End of Smallpox.

PMID- 28492841
TI  - Skin Disease as Art.

PMID- 28492843
TI  - Spoken Language Production in Young Adults: Examining Syntactic Complexity.
AB  - Purpose: In this study, we examined syntactic complexity in the spoken language
      samples of young adults. Its purpose was to contribute to the expanding knowledge
      base in later language development and to begin building a normative database of
      language samples that potentially could be used to evaluate young adults with
      known or suspected language impairment. Method: Forty adults (mean age = 22
      years, 10 months) with typical language development participated in an interview
      that consisted of 3 speaking tasks: a general conversation about common, everyday
      topics; a narrative retelling task that involved fables; and a question-and
      answer, critical-thinking task about the fables. Each speaker's interview was
      audio-recorded, transcribed, broken into communication units, coded for main and
      subordinate clauses, entered into Systematic Analysis of Language Transcripts
      (Miller, Iglesias, & Nockerts, 2004), and analyzed for mean length of
      communication unit and clausal density. Results: Both the narrative and critical
      thinking tasks elicited significantly greater syntactic complexity than the
      conversational task. It was also found that syntactic complexity was
      significantly greater during the narrative task than the critical-thinking task.
      Conclusion: Syntactic complexity was best revealed by a narrative task that
      involved fables. The study offers benchmarks for language development during
      early adulthood.

PMID- 28492844
TI  - Antibiotic Overuse: Clinicians Are the Solution.

PMID- 28492845
TI  - A Simple, Effective Analogy to Elucidate the Mohs Micrographic Surgery Procedure
      The Peanut Butter Cup.

PMID- 28492846
TI  - A Large Right Shoulder Mass.

PMID- 28492847
TI  - Workplace Factors Associated With Burnout of Family Physicians.

PMID- 28492848
TI  - The Role of Vena Cava Filters for Injured Patients: Please Don't Throw the Baby
      Out With the Bathwater.

PMID- 28492850
TI  - Cancer Screening, Overdiagnosis, and Regulatory Capture.

PMID- 28492849
TI  - Language Development and Brain Magnetic Resonance Imaging Characteristics in
      Preschool Children With Cerebral Palsy.
AB  - Purpose: The purpose of this study was to investigate characteristics of language
      development in relation to brain magnetic resonance imaging (MRI) characteristics
      and the other contributing factors to language development in children with
      cerebral palsy (CP). Method: The study included 172 children with CP who
      underwent brain MRI and language assessments between 3 and 7 years of age. The
      MRI characteristics were categorized as normal, malformation, periventricular
      white matter lesion (PVWL), deep gray matter lesion, focal infarct,
      cortical/subcortical lesion, and others. Neurodevelopmental outcomes such as
      ambulatory status, manual ability, cognitive function, and accompanying
      impairments were assessed. Results: Both receptive and expressive language
      development quotients (DQs) were significantly related to PVWL or deep gray
      matter lesion severity. In multivariable analysis, only cognitive function was
      significantly related to receptive language development, whereas ambulatory
      status and cognitive function were significantly associated with expressive
      language development. More than one third of the children had a language
      developmental discrepancy between receptive and expressive DQs. Children with
      cortical/subcortical lesions were at high risk for this discrepancy. Conclusions:
      Cognitive function is a key factor for both receptive and expressive language
      development. In children with PVWL or deep gray matter lesion, lesion severity
      seems to be useful to predict language development.

PMID- 28492851
TI  - Colposcopic imaging using visible-light optical coherence tomography.
AB  - High-resolution colposcopic optical coherence tomography (OCT) provides key
      anatomical measures, such as thickness and minor traumatic injury of vaginal
      epithelium, of the female reproductive tract noninvasively. This information can
      be helpful in both fundamental investigations in animal models and disease
      screenings in humans. We present a fiber-based visible-light OCT and two probe
      designs for colposcopic application. One probe conducts circular scanning using a
      DC motor, and the other probe is capable of three-dimensional imaging over a 4.6
      * 4.6 - mm 2 area using a pair of galvo scanners. Using this colposcopic vis-OCT
      with both probes, we acquired high-resolution images from whole isolated macaque
      vaginal samples and identified biopsy lesions.

PMID- 28492853
TI  - Polarization gating based on Mueller matrices.
AB  - We present mathematical formulas generalizing polarization gating (PG)
      techniques. PG refers to a collection of imaging methods based on the combination
      of different controlled polarization channels. In particular, we show how using
      the measured Mueller matrix (MM) of a sample, a widespread number of PG
      configurations can be evaluated just from analytical expressions based on the MM
      coefficients. We also show the interest of controlling the helicity of the states
      of polarization used for PG-based metrology, as this parameter has an impact in
      the image contrast of samples. In addition, we highlight the interest of
      combining PG techniques with tools of data analysis related to the MM formalism,
      such as the well-known MM decompositions. The method discussed in this work is
      illustrated with the results of polarimetric measurements done on artificial
      phantoms and real ex-vivo tissues.

PMID- 28492852
TI  - Characterization and correction of the false-discovery rates in resting state
      connectivity using functional near-infrared spectroscopy.
AB  - Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging
      technique that uses low levels of red to near-infrared light to measure changes
      in cerebral blood oxygenation. Spontaneous (resting state) functional
      connectivity (sFC) has become a critical tool for cognitive neuroscience for
      understanding task-independent neural networks, revealing pertinent details
      differentiating healthy from disordered brain function, and discovering
      fluctuations in the synchronization of interacting individuals during
      hyperscanning paradigms. Two of the main challenges to sFC-NIRS analysis are (i)
      the slow temporal structure of both systemic physiology and the response of blood
      vessels, which introduces false spurious correlations, and (ii) motion-related
      artifacts that result from movement of the fNIRS sensors on the participants'
      head and can introduce non-normal and heavy-tailed noise structures. In this
      work, we systematically examine the false-discovery rates of several time- and
      frequency-domain metrics of functional connectivity for characterizing sFC-NIRS.
      Specifically, we detail the modifications to the statistical models of these
      methods needed to avoid high levels of false-discovery related to these two
      sources of noise in fNIRS. We compare these analysis procedures using both
      simulated and experimental resting-state fNIRS data. Our proposed robust
      correlation method has better performance in terms of being more reliable to the
      noise outliers due to the motion artifacts.

PMID- 28492854
TI  - Evidence of anti-inflammatory effect and percutaneous penetration of a topically
      applied fish oil preparation: a photoacoustic spectroscopy study.
AB  - This paper investigates the topical anti-inflammatory effect of a fish oil
      preparation (FOP) in a croton oil (CO) model of skin inflammation. The
      photoacoustic spectroscopy (PAS) was applied to estimate the percutaneous
      penetration of the FOP and as a model to evaluate the topical inflammatory
      response. After applying CO, the groups of mice received a topical application of
      a FOP on the left ear. The right ear received the vehicle that was used to dilute
      the CO. After 6 h, ear tissue was collected to determine the percent inhibition
      of edema, myeloperoxidase (MPO) activity, and cytokine levels and to perform PAS
      measurements. Treatment with FOP reduced edema and MPO activity, which was at
      least partially attributed to a decrease in the levels of tumor necrosis factor,
      interleukin- 1 ? , interleukin-6, keratinocyte-derived chemokine, and monocyte
      chemoattractant protein-1. The topically applied FOP penetrated into the tissue
      and decreased the area of the bands that characterize inflamed tissue. The
      present results demonstrated the topical anti-inflammatory effect of the FOP. PAS
      suggests that FOP anti-inflammatory activity is linked with its ability to
      penetrate through the skin.

PMID- 28492855
TI  - Incremental Cost-effectiveness of Proliferative Diabetic Retinopathy Treatments:
      The Certainty of Uncertainty.

PMID- 28492857
TI  - Inappropriate Comparator Group in Study of Selective Serotonin Reuptake
      Inhibitors and Risk for Intracranial Hemorrhage-Reply.

PMID- 28492856
TI  - Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and
      Women: A Clinical Practice Guideline Update From the American College of
      Physicians.
AB  - Description: This guideline updates the 2008 American College of Physicians (ACP)
      recommendations on treatment of low bone density and osteoporosis to prevent
      fractures in men and women. This guideline is endorsed by the American Academy of
      Family Physicians. Methods: The ACP Clinical Guidelines Committee based these
      recommendations on a systematic review of randomized controlled trials;
      systematic reviews; large observational studies (for adverse events); and case
      reports (for rare events) that were published between 2 January 2005 and 3 June
      2011. The review was updated to July 2016 by using a machine-learning method, and
      a limited update to October 2016 was done. Clinical outcomes evaluated were
      fractures and adverse events. This guideline focuses on the comparative benefits
      and risks of short- and long-term pharmacologic treatments for low bone density,
      including pharmaceutical prescriptions, calcium, vitamin D, and estrogen.
      Evidence was graded according to the GRADE (Grading of Recommendations
      Assessment, Development and Evaluation) system. Target Audience and Patient
      Population: The target audience for this guideline includes all clinicians. The
      target patient population includes men and women with low bone density and
      osteoporosis. Recommendation 1: ACP recommends that clinicians offer
      pharmacologic treatment with alendronate, risedronate, zoledronic acid, or
      denosumab to reduce the risk for hip and vertebral fractures in women who have
      known osteoporosis. (Grade: strong recommendation; high-quality evidence).
      Recommendation 2: ACP recommends that clinicians treat osteoporotic women with
      pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality
      evidence). Recommendation 3: ACP recommends that clinicians offer pharmacologic
      treatment with bisphosphonates to reduce the risk for vertebral fracture in men
      who have clinically recognized osteoporosis. (Grade: weak recommendation; low
      quality evidence). Recommendation 4: ACP recommends against bone density
      monitoring during the 5-year pharmacologic treatment period for osteoporosis in
      women. (Grade: weak recommendation; low-quality evidence). Recommendation 5: ACP
      recommends against using menopausal estrogen therapy or menopausal estrogen plus
      progestogen therapy or raloxifene for the treatment of osteoporosis in women.
      (Grade: strong recommendation; moderate-quality evidence). Recommendation 6: ACP
      recommends that clinicians should make the decision whether to treat osteopenic
      women 65 years of age or older who are at a high risk for fracture based on a
      discussion of patient preferences, fracture risk profile, and benefits, harms,
      and costs of medications. (Grade: weak recommendation; low-quality evidence).

PMID- 28492858
TI  - Clinical Practice Guidelines for Osteoporosis: Translating Data to Patients?

PMID- 28492859
TI  - Epinephrine Concentrations in EpiPens After the Expiration Date.

PMID- 28492860
TI  - Baseline Factors Associated With 6-Month Visual Acuity and Retinal Thickness
      Outcomes in Patients With Macular Edema Secondary to Central Retinal Vein
      Occlusion or Hemiretinal Vein Occlusion: SCORE2 Study Report 4.
AB  - Importance: Macular edema (ME) is the leading cause of decreased visual acuity
      (VA) associated with retinal vein occlusion (RVO). Identifying factors associated
      with better outcomes in RVO eyes treated with anti-vascular endothelial growth
      factor (VEGF) therapy may provide information useful in counseling patients.
      Objective: To investigate baseline characteristics associated with 6-month VA and
      central subfield thickness (CST) outcomes in participants in the Study of
      Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Design, Setting,
      and Participants: A total of 362 patients with central RVO or hemi-RVO were
      enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in
      a masked fashion to receive bevacizumab or aflibercept. At month 6, 348
      participants (96%) had VA outcomes measured and 335 participants (93%) had
      spectral domain optical coherence tomography outcomes measured. The current data
      analysis was conducted from February 27, 2017, to April 7, 2017. Interventions:
      Eyes were randomly assigned to receive an intravitreal injection of bevacizumab,
      1.25 mg, or aflibercept, 2.0 mg, at baseline and every 4 weeks, with the primary
      outcome measured at 6 months. Main Outcomes and Measures: Change from baseline in
      VA letter score (VALS), VALS gain of 15 or more, change from baseline in CST, CST
      less than 300 um, and resolution of ME. Baseline factors associated with 6-month
      outcome at the 0.05 level in univariate regressions were included in multivariate
      regressions, with those significant after multiplicity control by the Hochberg
      method reported. Results: The mean (SD) age of patients was 69 (12) years, and
      43% were women. Younger patient age (odds ratio [OR], 0.95 per year of age; 95%
      CI, 0.93-0.98; P = .007) and lower baseline VALS (OR, 0.96 per letter; 95% CI,
      0.94-0.98; P < .001) were associated with a 6-month VALS gain of 15 or greater.
      Compared with bevacizumab, aflibercept treatment was associated with a higher
      odds of ME resolution (OR, 3.59; 95% CI, 2.22-5.80; P < .001) and CST less than
      300 um (OR,  5.30; 95% CI, 2.40-11.67; P = .001), but not with a better VA
      outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF
      treatment prior to study participation (OR, 0.33; 95% CI, 0.17-0.64; P = .03).
      Conclusions and Relevance: In eyes treated with bevacizumab or aflibercept,
      younger age and worse baseline VALS were associated with better 6-month VA
      outcomes. Aflibercept treatment was associated with more favorable spectral
      domain optical coherence tomography outcomes but not VA outcomes. These findings
      may be useful in assessing expected response at month 6 after monthly injection
      of anti-VEGF agents for treating ME due to CRVO and HRVO. Trial Registration:
      clinicaltrials.gov Identifier: NCT01969708.

PMID- 28492861
TI  - Vena Cava Filter Use in Trauma and Rates of Pulmonary Embolism, 2003-2015.
AB  - Importance: Vena cava filter (VCF) placement for pulmonary embolism (PE)
      prophylaxis in trauma is controversial. Limited research exists detailing trends
      in VCF use and occurrence of PE over time. Objective: To analyze state and
      nationwide temporal trends in VCF placement and PE occurrence from 2003 to 2015
      using available data sets. Design, Setting, and Participants: A retrospective
      trauma cohort study was conducted using data from the Pennsylvania Trauma Outcome
      Study (PTOS) (461 974 patients from 2003 to 2015), the National Trauma Data Bank
      (NTDB) (5 755 095 patients from 2003 to 2014), and the National (Nationwide)
      Inpatient Sample (NIS) (24 449 476 patients from 2003 to 2013) databases. Main
      Outcomes and Measures: Temporal trends in VCF placement and PE rates, filter type
      (prophylactic or therapeutic), and established predictors of PE (obesity,
      pregnancy, cancer, deep vein thrombosis, major procedure, spinal cord paralysis,
      venous injury, lower extremity fracture, pelvic fracture, central line,
      intracranial hemorrhage, and blood transfusion). Prophylactic filters were
      defined as VCFs placed before or without an existing PE, while therapeutic
      filters were defined as VCFs placed after a PE. Results: Of the 461 974 patients
      in PTOS, the mean (SD) age was 47.2 (26.4) and 61.6% (284 621) were men; of the 5
      755 095 patients in NTDB, the mean age (SD) was 42.0 (24.3) and 63.7% (3 666 504)
      were men; and of the 24 449 476 patients in NIS, the mean (SD) age was 58.0
      (25.2) and 49.7% (12 160 231) were men. Of patients receiving a filter (11 405 in
      the PTOS, 71 029 in the NTDB, and 189 957 in the NIS), most were prophylactic
      VCFs (93.6% in the PTOS, 93.5% in the NTDB, and 93.3% in the NIS). Unadjusted and
      adjusted temporal trends for the PTOS and NTDB showed initial increases in filter
      placement followed by significant declines (unadjusted reductions in VCF
      placement rates, 76.8% in the PTOS and 53.3% in the NTDB). The NIS demonstrated a
      similar unadjusted trend, with a slight increase and modest decline (22.2%) in
      VCF placement rates over time; however, adjusted trends showed a slight but
      significant increase in filter rates. Adjusted PE rates for the PTOS and NTDB
      showed significant initial increases followed by slight decreases, with limited
      variation during the declining filter use periods. The NIS showed an initial
      increase in PE rates followed by a period of stagnation. Conclusions and
      Relevance: Despite a precipitous decline of VCF use in trauma, PE rates remained
      unchanged during this period. Taking this association into consideration, VCFs
      may have limited utility in influencing rates of PE. More judicious
      identification of at-risk patients is warranted to determine individuals who
      would most benefit from a VCF.

PMID- 28492863
TI  - Understanding the Emergence of Chronic Posttraumatic Stress Disorder Through
      Acute Stress Symptom Networks.

PMID- 28492862
TI  - Establishing Baseline Normative Values for the Child Sport Concussion Assessment
      Tool.
AB  - Importance: The Child Sport Concussion Assessment Tool (SCAT3) is a
      postconcussion sideline assessment tool measuring symptoms, cognition, and
      balance in preadolescent children. Minimal normative baseline data exist to aid
      decision making in clinical and athletic settings. Objective: To collect
      normative baseline data for the Child SCAT3 in a large cohort of young athletes.
      Design, Setting, and Participants: A cross-sectional study was conducted from May
      31 to August 12, 2014, at various sporting events (basketball, soccer, baseball,
      and swimming) in Central Wisconsin among children 5 to 13 years of age who were
      English-speaking and did not report a lower leg injury within the past 2 months
      or a concussion within the past month. Data were analyzed between October 8,
      2014, and September 12, 2016. Main Outcomes and Measures: All Child SCAT3
      components were assessed: child and parent report of symptom number and severity,
      cognition (Standardized Assessment of Concussion-child version [SAC-C]), and
      balance (modified Balance Error Scoring System [mBESS] and tandem gait). Summary
      statistics, mean differences, and effect sizes were calculated for each test
      component. Results: Participants included 478 children (234 girls and 241 boys;
      mean [SD] age, 9.9 [1.9] years]) and their parents. Age had the largest effect on
      all Child SCAT3 components, with children 5 to 7 years of age reporting higher
      mean (SD) symptom severity scores compared with those 11 to 13 years of age (18.2
      [10.0] vs 11.3 [9.0]; mean difference, 6.86 [95% CI, 4.22-9.50]; effect size,
      0.74) and performing more poorly on the total SAC-C (mean [SD] score, 19.5 [5.1]
      vs 26.1 [2.1]; mean difference, -6.59 [95% CI, -7.49 to -5.68]; effect size, 
      2.1), mBESS (mean [SD] score, 1.67 [1.8] vs 0.76 [1.2]; mean difference, 0.91
      [95% CI, 0.53-1.29]; effect size, 0.68), and tandem gait (mean [SD] time, 22.2
      [8.3] vs 14.0 [3.7] seconds; mean difference, 8.23 seconds [95% CI, 6.63-9.82];
      effect size, 1.55). Sex had a small effect on the mean (SD) number and severity
      of symptoms reported by the child (severity: boys, 15.1 [9.8] vs girls, 11.8
      [9.2]; mean difference, 3.31 [95% CI, 1.60-5.02]; effect size, 0.35), mean (SD)
      number and severity of symptoms reported by the parent (severity: boys, 11.1
      [7.7] vs girls, 9.4 [8.1]; mean difference, 1.63 [95% CI, 0.21-3.05]; effect
      size, 0.21), mean (SD) total SAC-C score (boys, 23.9 [3.9] vs girls, 24.9 [3.5];
      mean difference, -0.92 [95% CI, -1.61 to -0.23]; effect size, -0.25), and mean
      (SD) mBESS score (boys, 1.21 [1.5] vs girls, 0.71 [1.0]; mean difference, 0.50
      [95% CI, 0.27-0.74]; effect size, 0.38). Conclusions and Relevance: Child SCAT3
      baseline normative symptom, cognitive, and balance scores were different, with a
      large main effect for age and a small effect for sex. These findings may assist
      health care professionals with interpretation of Child SCAT3 scores for young
      athletes with a concussion in athletic and clinical settings.

PMID- 28492864
TI  - Induction of Immune Reaction in Benign Melanocytic Nevi Without Halo During
      Nivolumab Therapy in a Patient With Melanoma.

PMID- 28492866
TI  - Response to de Wit et al., 2016, "Characteristics of Auditory Processing
      Disorders: A Systematic Review".
AB  - Purpose: This letter to the editor is in response to a review by de Wit et al.
      (2016), "Characteristics of Auditory Processing Disorders: A Systematic Review,"
      published in April 2016 by Journal of Speech, Language, and Hearing Research.
      Conclusion: The author argues that the conclusions in the de Wit et al. (2016)
      review are unfortunate in light of advances made in the clinical diagnosis and
      treatment of bottom-up auditory processing disorders in children.

PMID- 28492867
TI  - Distracted Driving With Attention-Deficit/Hyperactivity Disorder.

PMID- 28492865
TI  - The Relationship Between Iron Deficiency Anemia and Sensorineural Hearing Loss in
      the Pediatric and Adolescent Population.
AB  - Purpose: A correlation between iron deficiency anemia (IDA) and sudden
      sensorineural hearing loss (SNHL) was described in adults. In this study, we
      examined if there is a relationship between IDA and hearing loss in the pediatric
      population. Method: This was a retrospective cohort study of data collected from
      the Informatics for Integrating Biology and the Bedside database from 2011 to
      2016. Children and adolescents 4-21 years old seen at Penn State Milton S.
      Hershey Medical Center, Hershey, PA, were examined for hearing loss and IDA
      status. Hearing loss was determined by International Classification of Disease-9
      and -10 codes, and IDA was determined by both low hemoglobin and serum ferritin
      levels for age and sex. Results: We identified 20,113 patients. Prevalence of
      hearing loss and IDA was 1.7% and 2.3%, respectively. The prevalence of all
      hearing loss was 3.0% in the IDA cohort and 1.7% in those without IDA. Children
      and adolescents with IDA are at increased odds of developing SNHL (adjusted odds
      ratio: 3.67, 95% CI [1.60-7.30]). Conclusions: Children with IDA demonstrate
      increased likelihood of SNHL. Although correction of IDA in those with hearing
      loss has yet to be linked to improvements in hearing outcomes, screening for and
      correcting IDA among pediatric patients will positively affect overall health
      status. : Supplemental Material: https://doi.org/10.23641/asha.5087071.

PMID- 28492869
TI  - Effects of Magnification on Emotion Perception in Patients With Age-Related
      Macular Degeneration.
AB  - Purpose: Individuals with low vision often experience difficulties in performing
      tasks of daily living, such as face perception. This leads them to having
      difficulties with social interactions, as they can no longer correctly perceive
      the emotion of others. The present study investigated the effects of
      magnification on face perception in participants with age-related macular
      degeneration (AMD), and their ability to detect and categorize emotions. It was
      hypothesized that patients with AMD would be less accurate in comparison to
      healthy controls, but that magnification would improve their performance to that
      of controls. Methods: Faces containing happy, angry, or neutral emotion were both
      doubled (equivalent of arm's length distance) and decreased by half in size
      (equivalent of across the street). The ability to detect and to discriminate
      emotional content was compared between 20 AMD patients and 7 age-matched
      controls. Eye movements were recorded while conducting both tasks. Results:
      Regardless of stimulus size, when compared to controls, we observed that
      individuals with AMD consistently performed with lower accuracy in both emotion
      detection and categorization tasks. Moreover, having images undergo a 2-fold
      increase in size did improve performance, but did not equate AMD participants'
      performance to that of the controls in either the emotion detection or
      categorization task. Eye movements in AMD participants were highly variable in
      position compared to controls. Conclusions: The data suggest that magnification
      alone does not appear to be the answer for improving emotion perception within
      individuals with low vision. Next steps should include an evaluation of the
      effects of viewing strategy.

PMID- 28492870
TI  - Radiologic Parameters of Orbital Bone Remodeling in Thyroid Eye Disease.
AB  - Purpose: To radiologically examine for the presence of bony remodeling of the
      orbit in thyroid eye disease (TED). Methods: Computed tomography (CT) scans of
      248 orbits of 124 patients with TED and 185 orbits of 138 controls were
      retrospectively reviewed, and the following parameters measured: the angle of the
      inferomedial orbital strut (AIOS), the angle of the medial wall (AMW), and the
      diameters of the extraocular muscles. The association of TED with the AIOS or AMW
      was analyzed with linear regression models, and the correlations between the AMW
      or AIOS measurements with the extraocular muscle measurements were determined.
      Results: Overall, the AIOS was found to be larger (P < 0.001) and the AMW smaller
      (P = 0.045) in patients with TED compared to controls. After adjusting for age
      and sex, the larger AIOS in TED remained significant (P < 0.001), but the smaller
      AMW in TED patients was no longer significant (P = 0.07). There was a negative
      correlation between AMW and the calculated average cross-sectional area of the
      medial rectus in TED (r = -0.23, P = 0.01). Conclusions: A difference in the
      structure of the bony orbit in TED compared to controls may be demonstrated by
      the AIOS and AMW radiological parameters. This likely represents the presence of
      bony remodeling in TED, which may be related to the expansion of the intraorbital
      soft tissue volume.

PMID- 28492868
TI  - Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic
      Ventricular Tachycardia: A Randomized Clinical Trial.
AB  - Importance: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a
      potentially lethal genetic arrhythmia syndrome characterized by polymorphic
      ventricular tachycardia with physical or emotional stress, for which current
      therapy with beta-blockers is incompletely effective. Flecainide acetate directly
      suppresses sarcoplasmic reticulum calcium release-the cellular mechanism
      responsible for triggering ventricular arrhythmias in CPVT-but has never been
      assessed prospectively. Objective: To determine whether flecainide dosed to
      therapeutic levels and added to beta-blocker therapy is superior to beta-blocker
      therapy alone for the prevention of exercise-induced arrhythmias in CPVT. Design,
      Setting, and Participants: This investigator-initiated, multicenter, single
      blind, placebo-controlled crossover clinical trial was conducted from December
      19, 2011, through December 29, 2015, with a midtrial protocol change at 10 US
      sites. Patients with a clinical diagnosis of CPVT and an implantable cardioverter
      defibrillator underwent a baseline exercise test while receiving maximally
      tolerated beta-blocker therapy that was continued throughout the trial. Patients
      were then randomized to treatment A (flecainide or placebo) for 3 months,
      followed by exercise testing. After a 1-week washout period, patients crossed
      over to treatment B (placebo or flecainide) for 3 months, followed by exercise
      testing. Interventions: Patients received oral flecainide or placebo twice daily,
      with the dosage guided by trough serum levels. Main Outcomes and Measures: The
      primary end point of ventricular arrhythmias during exercise was compared between
      the flecainide and placebo arms. Exercise tests were scored on an ordinal scale
      of worst ventricular arrhythmia observed (0 indicates no ectopy; 1, isolated
      premature ventricular beats; 2, bigeminy; 3, couplets; and 4, nonsustained
      ventricular tachycardia). Results: Of 14 patients (7 males and 7 females; median
      age, 16 years [interquartile range, 15.0-22.5 years]) randomized, 13 completed
      the study. The median baseline exercise test score was 3.0 (range, 0-4), with no
      difference noted between the baseline and placebo (median, 2.5; range, 0-4)
      exercise scores. The median ventricular arrhythmia score during exercise was
      significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for
      placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%).
      Overall and serious adverse events did not differ between the flecainide and
      placebo arms. Conclusions and Relevance: In this randomized clinical trial of
      patients with CPVT, flecainide plus beta-blocker significantly reduced
      ventricular ectopy during exercise compared with placebo plus beta-blocker and
      beta-blocker alone. Trial Registration: clinicaltrials.gov Identifier:
      NCT01117454.

PMID- 28492871
TI  - Risk Factors for Posterior Subcapsular Cataract in Retinitis Pigmentosa.
AB  - Purpose: Posterior subcapsular cataract (PSC) is a frequent complication in
      patients with retinitis pigmentosa (RP). The risk factors for PSC formation in RP
      are largely unknown. The purpose of this study was to investigate the risk
      factors for PSC. Methods: We retrospectively studied a total of 322 eyes of 173
      patients who were diagnosed with typical RP. We considered the following possible
      risk factors for PSC: age, sex, hypertension, diabetes mellitus, high myopia,
      asthma, history of steroid intake, and aqueous flare. Aqueous flare values were
      measured consecutively in 2012 and 2013 using a laser flare cell meter. The lens
      including PSC was examined with a slit lamp after dilation with tropicamide 1%
      and phenylephrine 2.5%. Results: The geometric mean values of aqueous flare and
      mean values of visual acuity were significantly higher for the RP patients with
      PSC compared to those without PSC (P = 0.0003, P = 0.0004, respectively). When
      the aqueous flare values were assessed continuously, each 1-log-transformed
      increase in flare levels was associated with an elevation of the likelihood of
      having PSC after multivariable adjustment (odds ratio: 1.71; 95% confidence
      interval: 1.05-2.77). There were no significant associations of the other
      possible risk factors with PSC. Conclusions: Our analysis demonstrated that
      elevated aqueous flare is a significant risk factor for PSC formation. This
      result might provide insights into the association of inflammation and the
      pathogenesis of PSC formation in RP.

PMID- 28492872
TI  - Urinary Isoprostane Levels and Age-Related Macular Degeneration.
AB  - Purpose: Oxidative stress, characterized by an excessive production of reactive
      oxygen intermediates has been suggested to play a role in the pathogenesis of age
      related macular degeneration (AMD). We examined the association of urinary F2
      isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable
      marker of oxidative damage with AMD. Methods: We included 238 adults with AMD and
      390 age- and sex-matched controls without AMD who participated in a population
      based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009
      2011). AMD was graded from retinal photographs using the Wisconsin Age-Related
      Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were
      measured by gas chromatography mass spectrometry (GC-MS). The association between
      F2-IsoPs and AMD was examined using unconditional logistic regression models
      adjusted for potential confounders including smoking, body mass index (BMI),
      blood pressure, total and high-density lipoprotein cholesterol, and history of
      cardiovascular disease. Results: Higher levels of F2-IsoPs were associated with
      AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2
      IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles
      2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94),
      respectively. In subgroup analyses comparing Q4 to Q1, this association was
      stronger in women, those with BMI less than 25 kg/m2 and those with hypertension,
      but no significant interaction was found (P interaction > 0.1 for each strata).
      Conclusions: Higher levels of urinary F2-IsoPs levels were associated with AMD
      independent of potential confounders in Chinese adults.

PMID- 28492873
TI  - Sphingosine-1-Phosphate Mediates Fibrosis in Orbital Fibroblasts in Graves'
      Orbitopathy.
AB  - Purpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis
      in orbital fibroblasts in Graves' orbitopathy (GO). Methods: Orbital fibroblasts
      were cultured from orbital adipose/connective tissues of patients with GO and
      healthy control subjects. Effects of treatment with TGF-beta and cigarette smoke
      extract (CSE) on S1P receptor (S1PR) messenger RNA (mRNA) and S1P expression were
      evaluated by real-time polymerase chain reaction and Western blotting. To
      evaluate the role of S1P in fibrosis, cells were pretreated with W146 (S1PR1
      antagonist); JTE013 (S1PR2 antagonist); FTY720 (S1PR1 modulator); or 5C
      (sphingosine kinase-1 blocker) for 1 hour before stimulation with TGF-beta, CSE,
      or IL-1beta. Expression of fibrosis-related proteins (collagen Ialpha,
      fibronectin, and alpha-smooth muscle actin [SMA]) and tissue remodeling-related
      proteins (matrix metalloproteinases [MMPs] and tissue inhibitor of
      metalloproteinase [TIMP]-1) was then evaluated by Western blotting. Results:
      Expression levels of S1PR mRNA and S1P in GO orbital fibroblasts increased upon
      TGF-beta and CSE treatment. Treatment with S1PR blockers and 5C inhibited TGF
      beta and CSE-induced expression of collagen Ialpha, fibronectin, and alpha-SMA,
      as well as IL-1beta-induced expression of MMP-1, MMP-2, MMP-9, and TIMP-1.
      Exogenous S1P treatment without profibrotic stimulants upregulated collagen
      Ialpha, fibronectin, alpha-SMA, MMP-1, MMP-2, MMP-9, and TIMP-1 expression in a
      dose-dependent manner. Conclusions: Blocking of S1PR activity and inhibition of
      S1P synthesis led to decreased expression of fibrosis and tissue remodeling
      related proteins in primary cultures of orbital fibroblasts derived from patients
      with GO. Thus, modulation of S1P activity might have therapeutic potential in the
      suppression of fibrosis in GO.

PMID- 28492875
TI  - The USPSTF Recommendation on Thyroid Cancer Screening: Don't "Check Your Neck".

PMID- 28492874
TI  - Peripapillary Retinal Pigment Epithelium Layer Shape Changes From Acetazolamide
      Treatment in the Idiopathic Intracranial Hypertension Treatment Trial.
AB  - Purpose: Recent studies indicate that the amount of deformation of the
      peripapillary retinal pigment epithelium and Bruch's membrane (pRPE/BM) toward or
      away from the vitreous may reflect acute changes in cerebrospinal fluid pressure.
      The study purpose is to determine if changes in optic-nerve-head (ONH) shape
      reflect a treatment effect (acetazolamide/placebo + weight management) using the
      optical coherence tomography (OCT) substudy of the Idiopathic Intracranial
      Hypertension Treatment Trial (IIHTT) at baseline, 3, and 6 months. Methods: The
      pRPE/BM shape deformation was quantified and compared with ONH volume,
      peripapillary retinal nerve fiber layer (pRNFL), and total retinal (pTR)
      thicknesses in the acetazolamide group (39 subjects) and placebo group (31
      subjects) at baseline, 3, and 6 months. Results: Mean changes of the pRPE/BM
      shape measure were significant and in the positive direction (away from the
      vitreous) for the acetazolamide group (P < 0.01), but not for the placebo group.
      The three OCT measures reflecting the reduction of optic disc swelling were
      significant in both treatment groups but greater in the acetazolamide group (P <
      0.01). Conclusions: Change in the pRPE/BM shape away from the vitreous reflects
      the effect of acetazolamide + weight management in reducing the pressure
      differential between the intraocular and retrobulbar arachnoid space. Weight
      management alone was also associated with a decrease in optic nerve volume/edema
      but without a significant change in the pRPE/BM shape, implying an alternative
      mechanism for improvement in papilledema and axoplasmic flow, independent of a
      reduction in the pressure differential. (ClinicalTrials.gov number,
      NCT01003639.).

PMID- 28492876
TI  - Pulmonary Embolism and Deep Venous Thrombosis in Patients Hospitalized With
      Syncope: A Multicenter Cross-sectional Study in Toronto, Ontario, Canada.

PMID- 28492878
TI  - Investigation Into Opioid Crisis Targets Drug Companies.

PMID- 28492877
TI  - The Center Cannot Hold: Medicine, Music, and the Mind.

PMID- 28492880
TI  - Maker of Duodenoscopes Under Scrutiny Again.

PMID- 28492879
TI  - Hearing Focuses on Proposed Cuts in Cancer Research.

PMID- 28492881
TI  - Incorrect Unit of Measure.

PMID- 28492882
TI  - Misspelling of Author Name.

PMID- 28492883
TI  - Incorrect Funder.

PMID- 28492884
TI  - Introducing "Genomics and Precision Health".

PMID- 28492885
TI  - Treatment of KRAS-Mutant Non-Small Cell Lung Cancer: The End of the Beginning for
      Targeted Therapies.

PMID- 28492886
TI  - How to Look for Thyroid Cancer.

PMID- 28492888
TI  - Finding the Rare Pathogenic Variants in a Human Genome.

PMID- 28492889
TI  - Medicolegal.

PMID- 28492890
TI  - Association Between Long-term Quinine Exposure and All-Cause Mortality.

PMID- 28492891
TI  - Use of the qSOFA Score in the Emergency Department.

PMID- 28492892
TI  - Outlier in Analysis of Cancer Mortality by US County.

PMID- 28492893
TI  - Legal Complexities of Global Vaccine Compensation Systems.

PMID- 28492894
TI  - Use of the qSOFA Score in the Emergency Department-Reply.

PMID- 28492895
TI  - Outlier in Analysis of Cancer Mortality by US County-Reply.

PMID- 28492896
TI  - Legal Complexities of Global Vaccine Compensation Systems-Reply.

PMID- 28492897
TI  - Farewell to a Cancer That Never Was.

PMID- 28492898
TI  - Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free
      Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The
      SELECT-1 Randomized Clinical Trial.
AB  - Importance: There are no specifically approved targeted therapies for the most
      common genomically defined subset of non-small cell lung cancer (NSCLC), KRAS
      mutant lung cancer. Objective: To compare efficacy of the mitogen-activated
      protein kinase kinase (MEK) inhibitor selumetinib + docetaxel with docetaxel
      alone as a second-line therapy for advanced KRAS-mutant NSCLC. Design, Setting,
      and Participants: Multinational, randomized clinical trial conducted at 202 sites
      across 25 countries from October 2013 through January 2016. Of 3323 patients with
      advanced NSCLC and disease progression following first-line anticancer therapy
      tested for a KRAS mutation, 866 were enrolled and 510 randomized. Primary reason
      for exclusion was ineligibility. The data cutoff date for analysis was June 7,
      2016. Interventions: Patients were randomized 1:1; 254 to receive selumetinib +
      docetaxel and 256 to receive placebo + docetaxel. Main Outcomes and Measures:
      Primary end point was investigator assessed progression-free survival. Secondary
      end points included overall survival, objective response rate, duration of
      response, effects on disease-related symptoms, safety, and tolerability. Results:
      Of 510 randomized patients (mean age, 61.4 years [SD, 8.3]; women, 207 [41%]),
      505 patients (99%) received treatment and completed the study (251 received
      selumetinib + docetaxel; 254 received placebo + docetaxel). At the time of data
      cutoff, 447 patients (88%) had experienced a progression event and 346 deaths
      (68%) had occurred. Median progression-free survival was 3.9 months
      (interquartile range [IQR], 1.5-5.9) with selumetinib + docetaxel and 2.8 months
      (IQR, 1.4-5.5) with placebo + docetaxel (difference, 1.1 months; hazard ratio
      [HR], 0.93 [95% CI, 0.77-1.12]; P = .44). Median overall survival was 8.7 months
      (IQR, 3.6-16.8) with selumetinib + docetaxel and 7.9 months (IQR, 3.8-20.1) with
      placebo + docetaxel (difference, 0.9 months; HR, 1.05 [95% CI, 0.85-1.30]; P =
      .64). Objective response rate was 20.1% with selumetinib + docetaxel and 13.7%
      with placebo + docetaxel (difference, 6.4%; odds ratio, 1.61 [95% CI, 1.00-2.62];
      P = .05). Median duration of response was 2.9 months (IQR, 1.7-4.8; 95% CI, 2.7
      4.1) with selumetinib + docetaxel and 4.5 months (IQR, 2.3-7.3; 95% CI, 2.8-5.6)
      with placebo + docetaxel. Adverse events of grade 3 or higher were more frequent
      with selumetinib + docetaxel (169 adverse events [67%] for selumetinib +
      docetaxel vs 115 adverse events [45%] for placebo + docetaxel; difference, 22%).
      Conclusions and Relevance: Among patients with previously treated advanced KRAS
      mutant non-small cell lung cancer, addition of selumetinib to docetaxel did not
      improve progression-free survival compared with docetaxel alone. Trial
      Registration: clinicaltrials.gov: NCT01933932.

PMID- 28492900
TI  - JAMA patient page. Screening for Thyroid Cancer.

PMID- 28492899
TI  - Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and
      Drug Administration Between 2001 and 2010.
AB  - Importance: Postmarket safety events of novel pharmaceuticals and biologics occur
      when new safety risks are identified after initial regulatory approval of these
      therapeutics. These safety events can change how novel therapeutics are used in
      clinical practice and inform patient and clinician decision making. Objectives:
      To characterize the frequency of postmarket safety events among novel
      therapeutics approved by the US Food and Drug Administration (FDA), and to
      examine whether any novel therapeutic characteristics known at the time of FDA
      approval were associated with increased risk. Design and Setting: Cohort study of
      all novel therapeutics approved by the FDA between January 1, 2001, and December
      31, 2010, followed up through February 28, 2017. Exposures: Novel therapeutic
      characteristics known at the time of FDA approval, including drug class,
      therapeutic area, priority review, accelerated approval, orphan status, near
      regulatory deadline approval, and regulatory review time. Main Outcomes and
      Measures: A composite of (1) withdrawals due to safety concerns, (2) FDA issuance
      of incremental boxed warnings added in the postmarket period, and (3) FDA
      issuance of safety communications. Results: From 2001 through 2010, the FDA
      approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There
      were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59
      safety communications) during a median follow-up period of 11.7 years
      (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel
      therapeutics. The median time from approval to first postmarket safety event was
      4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected
      by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In
      multivariable analysis, postmarket safety events were statistically significantly
      more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06
      3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease
      (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval
      (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near-regulatory deadline
      approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically
      significantly less frequent among those with regulatory review times less than
      200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance:
      Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were
      affected by a postmarket safety event. Biologics, psychiatric therapeutics, and
      accelerated and near-regulatory deadline approval were statistically
      significantly associated with higher rates of events, highlighting the need for
      continuous monitoring of the safety of novel therapeutics throughout their life
      cycle.

PMID- 28492902
TI  - A piece of my mind: Medical Education and the Minority Tax.

PMID- 28492904
TI  - Screening for Thyroid Cancer: Updated Evidence Report and Systematic Review for
      the US Preventive Services Task Force.
AB  - Importance: The incidence of detected thyroid cancer cases has been increasing in
      the United States since 1975. The majority of thyroid cancers are differentiated
      cancers with excellent prognosis and long-term survival. Objective: To
      systematically review the benefits and harms associated with thyroid cancer
      screening and treatment of early thyroid cancer in asymptomatic adults to inform
      the US Preventive Services Task Force. Data Sources: Searches of MEDLINE, PubMed,
      and the Cochrane Central Register of Controlled Trials for relevant studies
      published from January 1966 through January 2016, with active surveillance
      through December 2016. Study Selection: English-language studies conducted in
      asymptomatic adult populations. Data Extraction and Synthesis: Two reviewers
      independently appraised the articles and extracted relevant study data from fair-
      or good-quality studies. Random-effects meta-analyses were conducted to pool
      surgical harms. Main Outcomes and Measures: Thyroid cancer morbidity and
      mortality, test accuracy to detect thyroid nodules or thyroid cancer, and harms
      resulting from screening (including overdiagnosis) or treatment of thyroid
      cancer. Results: Of 10 424 abstracts, 707 full-text articles were reviewed, and
      67 studies were included for this review. No fair- to good-quality studies
      directly examined the benefit of thyroid cancer screening. In 2 studies (n =
      354), neck palpation was not sensitive to detect thyroid nodules. In 2
      methodologically limited studies (n = 243), a combination of selected high-risk
      sonographic features was specific for thyroid malignancy. Three studies (n =
      5894) directly addressed the harms of thyroid cancer screening, none of which
      suggested any serious harms from screening or ultrasound-guided fine-needle
      aspiration. No screening studies directly examined the risk of overdiagnosis. Two
      observational studies (n = 39 211) included cohorts of persons treated for well
      differentiated thyroid cancer and persons with no surgery or surveillance;
      however, these studies did not adjust for confounders and therefore were not
      designed to determine if earlier or immediate treatment vs delayed or no surgical
      treatment improves patient outcomes. Based on 36 studies (n = 43 295), the 95% CI
      for the rate of surgical harm was 2.12 to 5.93 cases of permanent
      hypoparathyroidism per 100 thyroidectomies and 0.99 to 2.13 cases of recurrent
      laryngeal nerve palsy per 100 operations. Based on 16 studies (n = 291 796),
      treatment of differentiated thyroid cancer with radioactive iodine is associated
      with a small increase in risk of second primary malignancies and with increased
      risk of permanent adverse effects on the salivary gland, such as dry mouth.
      Conclusions and Relevance: Although ultrasonography of the neck using high-risk
      sonographic characteristics plus follow-up cytology from fine-needle aspiration
      can identify thyroid cancers, it is unclear if population-based or targeted
      screening can decrease mortality rates or improve important patient health
      outcomes. Screening that results in the identification of indolent thyroid
      cancers, and treatment of these overdiagnosed cancers, may increase the risk of
      patient harms.

PMID- 28492906
TI  - How Much Do You Drink?

PMID- 28492905
TI  - Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation
      Statement.
AB  - Importance: The incidence of thyroid cancer detection has increased by 4.5% per
      year over the last 10 years, faster than for any other cancer, but without a
      corresponding change in the mortality rate. In 2013, the incidence rate of
      thyroid cancer in the United States was 15.3 cases per 100 000 persons. Most
      cases of thyroid cancer have a good prognosis; the 5-year survival rate for
      thyroid cancer overall is 98.1%. Objective: To update the US Preventive Services
      Task Force (USPSTF) recommendation on screening for thyroid cancer. Evidence
      Review: The USPSTF reviewed the evidence on the benefits and harms of screening
      for thyroid cancer in asymptomatic adults, the diagnostic accuracy of screening
      (including neck palpation and ultrasound), and the benefits and harms of
      treatment of screen-detected thyroid cancer. Findings: The USPSTF found
      inadequate direct evidence on the benefits of screening but determined that the
      magnitude of the overall benefits of screening and treatment can be bounded as no
      greater than small, given the relative rarity of thyroid cancer, the apparent
      lack of difference in outcomes between patients who are treated vs monitored (for
      the most common tumor types), and observational evidence showing no change in
      mortality over time after introduction of a mass screening program. The USPSTF
      found inadequate direct evidence on the harms of screening but determined that
      the overall magnitude of the harms of screening and treatment can be bounded as
      at least moderate, given adequate evidence of harms of treatment and indirect
      evidence that overdiagnosis and overtreatment are likely to be substantial with
      population-based screening. The USPSTF therefore determined that the net benefit
      of screening for thyroid cancer is negative. Conclusions and Recommendation: The
      USPSTF recommends against screening for thyroid cancer in asymptomatic adults. (D
      recommendation).

PMID- 28492908
TI  - A Path Beyond Advocacy to Improve Mental Health Services for Children and
      Families: Population Health Management.

PMID- 28492907
TI  - Medicaid's Impact on Overdose Rates.

PMID- 28492909
TI  - The Controversial Epidemiology of Left Ventricular Dysfunction in Patients With
      Myotonic Dystrophy Type 1.

PMID- 28492911
TI  - How Much Information Do People With Aphasia Convey via Gesture?
AB  - Purpose : People with aphasia (PWA) face significant challenges in verbally
      expressing their communicative intentions. Different types of gestures are
      produced spontaneously by PWA, and a potentially compensatory function of these
      gestures has been discussed. The current study aimed to investigate how much
      information PWA communicate through 3 types of gesture and the communicative
      effectiveness of such gestures. Method: Listeners without language impairment
      rated the information content of short video clips taken from PWA in
      conversation. Listeners were asked to rate communication within a speech-only
      condition and a gesture + speech condition. Results: The results revealed that
      the participants' interpretations of the communicative intentions expressed in
      the clips of PWA were significantly more accurate in the gesture + speech
      condition for all tested gesture types. Conclusion: It was concluded that all 3
      gesture types under investigation contributed to the expression of semantic
      meaning communicated by PWA. Gestures are an important communicative means for
      PWA and should be regarded as such by their interlocutors. Gestures have been
      shown to enhance listeners' interpretation of PWA's overall communication.

PMID- 28492910
TI  - Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular
      Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical
      Trial.
AB  - Importance: Studies have established the efficacy and safety of aflibercept for
      the treatment of macular edema due to central retinal vein occlusion. Bevacizumab
      is used off-label to treat this condition despite the absence of supporting data.
      Objective: To investigate whether bevacizumab is noninferior to aflibercept for
      the treatment of macular edema secondary to central retinal or hemiretinal vein
      occlusion. Design, Setting, and Participants: The SCORE2 randomized
      noninferiority clinical trial was conducted at 66 private practice or academic
      centers in the United States, and included 362 patients with macular edema due to
      central retinal or hemiretinal vein occlusion who were randomized 1:1 to receive
      aflibercept or bevacizumab. The first participant was randomized on September 17,
      2014, and the last month 6 visit occurred on May 6, 2016. Analyses included data
      available as of December 30, 2016. Interventions: Eyes were randomized to receive
      intravitreal injection of bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg;
      n = 180) every 4 weeks through month 6. Main Outcomes and Measures: The primary
      outcome was mean change in visual acuity (VA) letter score (VALS) from the
      randomization visit to the 6-month follow-up visit, based on the best-corrected
      electronic Early Treatment Diabetic Retinopathy Study VALS (scores range from 0
      100; higher scores indicate better VA). The noninferiority margin was 5 letters,
      and statistical testing for noninferiority was based on a 1-sided 97.5%
      confidence interval. Results: Among 362 randomized participants (mean [SD] age,
      69 [12] years; 157 [43.4%] women; mean [SD] VALS at baseline, 50.3 [15.2]
      [approximate Snellen VA 20/100]), 348 (96.1%) completed the month 6 follow-up
      visit. At month 6, the mean VALS was 69.3 (a mean increase from baseline of 18.6)
      in the bevacizumab group and 69.3 (a mean increase from baseline of 18.9) in the
      aflibercept group (model-based estimate of between-group difference, -0.14; 97.5%
      CI, -3.07 to infinity; P = .001 for noninferiority), meeting criteria for
      noninferiority. Ocular adverse events in the aflibercept group included 4
      participants with intraocular pressure (IOP) more than 10 mm Hg greater than
      baseline; ocular adverse events in the bevacizumab group included 1 participant
      with endophthalmitis (culture negative), 9 with IOP more than 10 mm Hg greater
      than baseline, 2 with IOP higher than 35 mm Hg, and 1 with angle-closure glaucoma
      not attributed to the study drug or procedure. Conclusions and Relevance: Among
      patients with macular edema due to central retinal or hemiretinal vein occlusion,
      intravitreal bevacizumab was noninferior to aflibercept with respect to visual
      acuity after 6 months of treatment.

PMID- 28492912
TI  - Auditory Verbal Working Memory as a Predictor of Speech Perception in Modulated
      Maskers in Listeners With Normal Hearing.
AB  - Purpose: Background noise can interfere with our ability to understand speech.
      Working memory capacity (WMC) has been shown to contribute to the perception of
      speech in modulated noise maskers. WMC has been assessed with a variety of
      auditory and visual tests, often pertaining to different components of working
      memory. This study assessed the relationship between speech perception in
      modulated maskers and components of auditory verbal working memory (AVWM) over a
      range of signal-to-noise ratios. Method: Speech perception in noise and AVWM were
      measured in 30 listeners (age range 31-67 years) with normal hearing. AVWM was
      estimated using forward digit recall, backward digit recall, and nonword
      repetition. Results: After controlling for the effects of age and average pure
      tone hearing threshold, speech perception in modulated maskers was related to
      individual differences in the phonological component of working memory (as
      assessed by nonword repetition) but only in the least favorable signal-to-noise
      ratio. The executive component of working memory (as assessed by backward digit)
      was not predictive of speech perception in any conditions. Conclusions: AVWM is
      predictive of the ability to benefit from temporal dips in modulated maskers:
      Listeners with greater phonological WMC are better able to correctly identify
      sentences in modulated noise backgrounds.

PMID- 28492913
TI  - Mental Health Outcomes After Having or Being Denied an Abortion-Reply.

PMID- 28492914
TI  - Antibiotic Prescribing for Nonbacterial Acute Upper Respiratory Infections in
      Elderly Persons.
AB  - Background: Reducing inappropriate antibiotic prescribing for acute upper
      respiratory tract infections (AURIs) requires a better understanding of the
      factors associated with this practice. Objective: To determine the prevalence of
      antibiotic prescribing for nonbacterial AURIs and whether prescribing rates
      varied by physician characteristics. Design: Retrospective analysis of linked
      administrative health care data. Setting: Primary care physician practices in
      Ontario, Canada (January-December 2012). Patients: Patients aged 66 years or
      older with nonbacterial AURIs. Patients with cancer or immunosuppressive
      conditions and residents of long-term care homes were excluded. Measurements:
      Antibiotic prescriptions for physician-diagnosed AURIs. A multivariable logistic
      regression model with generalized estimating equations was used to examine
      whether prescribing rates varied by physician characteristics, accounting for
      clustering of patients among physicians and adjusting for patient-level
      covariates. Results: The cohort included 8990 primary care physicians and 185 014
      patients who presented with a nonbacterial AURI, including the common cold
      (53.4%), acute bronchitis (31.3%), acute sinusitis (13.6%), or acute laryngitis
      (1.6%). Forty-six percent of patients received an antibiotic prescription; most
      prescriptions were for broad-spectrum agents (69.9% [95% CI, 69.6% to 70.2%]).
      Patients were more likely to receive prescriptions from mid- and late-career
      physicians than early-career physicians (rate difference, 5.1 percentage points
      [CI, 3.9 to 6.4 percentage points] and 4.6 percentage points [CI, 3.3 to 5.8
      percentage points], respectively), from physicians trained outside of Canada or
      the United States (3.6 percentage points [CI, 2.5 to 4.6 percentage points]), and
      from physicians who saw 25 to 44 patients per day or 45 or more patients per day
      than those who saw fewer than 25 patients per day (3.1 percentage points [CI, 2.1
      to 4.0 percentage points] and 4.1 percentage points [CI, 2.7 to 5.5 percentage
      points], respectively). Limitation: Physician rationale for prescribing was
      unknown. Conclusion: In this low-risk elderly cohort, 46% of patients with a
      nonbacterial AURI were prescribed antibiotics. Patients were more likely to
      receive prescriptions from mid- or late-career physicians with high patient
      volumes and from physicians who were trained outside of Canada or the United
      States. Primary Funding Source: Ontario Ministry of Health and Long-term Care,
      Academic Medical Organization of Southwestern Ontario, Schulich School of
      Medicine and Dentistry, Western University, and Lawson Health Research Institute.

PMID- 28492915
TI  - Sildenafil Treatment in Heart Failure With Preserved Ejection Fraction: Targeted
      Metabolomic Profiling in the RELAX Trial.
AB  - Importance: Phosphodiesterase-5 inhibition with sildenafil compared with a
      placebo had no effect on the exercise capacity or clinical status of patients
      with heart failure with preserved ejection fraction (HFpEF) in the
      PhosphodiesteRasE-5 Inhibition to Improve Clinical Status and Exercise Capacity
      in Diastolic Heart Failure with Preserved Ejection Fraction (RELAX) clinical
      trial. Metabolic impairments may explain the neutral results. Objective: To test
      the hypothesis that profiling metabolites in the RELAX trial would clarify the
      mechanisms of sildenafil effects and identify metabolites associated with
      clinical outcomes in HFpEF. Design, Setting, and Participants: Paired baseline
      and 24-week plasma samples of 160 stable outpatient individuals with HFpEF
      enrolled in the RELAX clinical trial were analyzed using flow injection tandem
      mass spectrometry (60 metabolites) and conventional assays (5 metabolites).
      Interventions: Sildenafil (n = 79) or a placebo (n = 81) administered orally at
      20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks.
      Main Outcomes and Measures: The primary measure was metabolite level changes
      between baseline and 24 weeks stratified by treatments. Secondary measures
      included correlations between metabolite level changes and clinical biomarkers
      and associations between baseline metabolite levels and the composite clinical
      score. Results: No metabolites changed between baseline and 24 weeks in the group
      treated with a placebo; however, 7 metabolites changed in the group treated with
      sildenafil, including decreased amino acids (alanine and proline; median change
      [25th-75th], -38.26 [-100.3 to 28.19] and -28.24 [-56.29 to 12.08], respectively;
      false discovery rate-adjusted P = .01 and .03, respectively), and increased short
      chain dicarboxylacylcarnitines glutaryl carnitine, octenedioyl carnitine, and
      adipoyl carnitine (median change, 6.19 [-3.37 to 14.18], 2.72 [-3 to 12.57], and
      10.72 [-11.23 to 29.57], respectively; false discovery rate-adjusted P = .01,
      .04, and .05, respectively), and 1 long-chain acylcarnitine metabolite (palmitoyl
      carnitine; median change, 7.83 [-5.64 to 26.99]; false discovery rate-adjusted P
      = .03). The increases in long-chain acylarnitine metabolites and short-chain
      dicarboxylacylcarnitines correlated with increases in endothelin-1 and
      creatinine/cystatin C, respectively. Higher baseline levels of short-chain
      dicarboxylacylcarnitine metabolite 3-hydroxyisovalerylcarnitine/malonylcarnitine
      and asparagine/aspartic acid were associated with worse clinical rank scores in
      both treatment groups (beta, -96.60, P = .001 and beta, -0.02, P = .01; after
      renal adjustment, P = .09 and .02, respectively). Conclusions and Relevance: Our
      study provides a potential mechanism for the effects of sildenafil that, through
      adverse effects on mitochondrial function and endoplasmic reticulum stress, could
      have contributed to the neutral trial results in RELAX. Short-chain
      dicarboxylacylcarnitine metabolites and asparagine/aspartic acid could serve as
      biomarkers associated with adverse clinical outcomes in HFpEF.

PMID- 28492916
TI  - Myocardial Fibrosis in Duchenne and Becker Muscular Dystrophy.

PMID- 28492917
TI  - Coverage of Magnetic Resonance Imaging for Patients With Cardiac Devices:
      Improving the Coverage With Evidence Development Program.

PMID- 28492919
TI  - Striving for Clarity About the Best Approach to Thyroid Cancer Screening and
      Treatment: Is the Pendulum Swinging Too Far?

PMID- 28492918
TI  - Association of a Primary Stroke Center Protocol for Suspected Stroke by Large
      Vessel Occlusion With Efficiency of Care and Patient Outcomes.
AB  - Importance: While prehospital triage to the closest comprehensive stroke center
      (CSC) may improve the delivery of care for patients with suspected emergent large
      vessel occlusion (ELVO), efficient systems of care must also exist for patients
      with ELVO who first present to a primary stroke center (PSC). Objective: To
      describe the association of a PSC protocol focused on 3 key steps (early CSC
      notification based on clinical severity, vessel imaging at the PSC, and cloud
      based image sharing) with the efficiency of care and the outcomes of patients
      with suspected ELVO who first present to a PSC. Design, Setting, and
      Participants: In this retrospective cohort study, 14 regional PSCs unfamiliar
      with the management of patients with ELVO were instructed on the use of the
      following protocol for patients presenting with a Los Angeles Motor Scale score 4
      or higher: (1) notify the CSC on arrival, (2) perform computed tomographic
      angiography concurrently with noncontract computed tomography of the brain and
      within 30 minutes of arrival, and (3) share imaging data with the CSC using a
      cloud-based platform. A total of 101 patients were transferred from regional PSCs
      to the CSC between July 1, 2015, and May 31, 2016, and received mechanical
      thrombectomy for acute ischemic stroke. The CSC serves approximately 1.7 million
      people and partners with 14 PSCs located between 6.4 and 73.6 km away. All
      consecutive patients with internal carotid artery or middle cerebral artery
      occlusions transferred over an 11-month period were reviewed, and they were
      divided into 2 groups based on whether the PSC protocol was partially or fully
      executed. Main Outcomes and Measures: The primary outcomes were efficiency
      measures including time from PSC door in to PSC door out, time from PSC door to
      CSC groin puncture, and 90-day modified Rankin Scale score (range, 0-6; scores of
      0-2 indicate a good outcome). Results: Although 101 patients were transferred,
      only 70 patients met the inclusion criteria during the study period. The protocol
      was partially executed for 48 patients (68.6%) (mean age, 77 years [interquartile
      range, 65-84 years]; 22 of the 48 patients [45.0%] were women) and fully executed
      for 22 patients (31.4%) (mean age, 76 years [interquartile range, 59-86 years];
      13 of the 22 patients [59.1%] were women). When fully executed, the protocol was
      associated with a reduction in the median time for PSC arrival to CSC groin
      puncture (from 151 minutes [95% CI, 141-166 minutes] to 111 minutes [95% CI, 88
      130 minutes]; P < .001). This was primarily related to an improvement in the time
      from PSC door in to door out that reduced from a median time of 104 minutes (95%
      CI, 82-112 minutes) to a median time of 64 minutes (95% CI, 51-71.0 minutes) (P <
      .001). When the protocol was fully executed, patients were twice as likely to
      have a favorable outcome (50% vs 25%, P < .04). Conclusions and Relevance: When
      fully implemented, a standardized protocol at PSCs for patients with suspected
      ELVO consisting of early CSC notification, computed tomographic angiography on
      arrival to the PSC, and cloud-based image sharing is associated with a reduction
      in time to groin puncture and improved outcomes.

PMID- 28492920
TI  - Cost-effectiveness of Intravitreous Ranibizumab Compared With Panretinal
      Photocoagulation for Proliferative Diabetic Retinopathy: Secondary Analysis From
      a Diabetic Retinopathy Clinical Research Network Randomized Clinical Trial.
AB  - Importance: The Diabetic Retinopathy Clinical Research Network Protocol S
      randomized clinical trial results suggest that ranibizumab is a reasonable
      treatment alternative to panretinal photocoagulation (PRP) when managing
      proliferative diabetic retinopathy (PDR), with or without concomitant baseline
      diabetic macular edema (DME). However, ranibizumab injections are costly. Thus,
      it would be useful to examine the relative cost-effectiveness of these 2
      treatment modalities. Objective: To evaluate incremental cost-effectiveness
      ratios of 0.5-mg ranibizumab therapy vs PRP for PDR. Design, Setting, and
      Participants: Preplanned secondary analysis using efficacy, safety, and resource
      utilization data through 2 years of follow-up at 55 US sites for 213 adults with
      PDR. Data were collected from February 2012 to January 2015. Interventions:
      Intravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks
      based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in
      both groups could receive ranibizumab for concomitant DME. Main Outcomes and
      Measures: Incremental cost-effectiveness ratios of ranibizumab compared with PRP
      evaluated within 2 prespecified subgroups for the study eye: with baseline vision
      impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision
      impairing DME. Results: The study included 305 adults with PDR, the mean age was
      52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and
      vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and
      25 to the PRP group (plus ranibizumab for DME). Among the remaining participants
      without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP
      groups, respectively. For participants with and without baseline vision-impairing
      DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared
      with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted
      life-year, respectively, over 2 years. Conclusions and Relevance: Over 2 years,
      compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50
      000/quality-adjusted life-year to $150 000/quality-adjusted life-year range
      frequently cited as cost-effective in the United States for eyes presenting with
      PDR and vision-impairing DME, but not for those with PDR without vision-impairing
      DME. Trial Registration: Clinicaltrials.gov Identifier: NCT01489189.

PMID- 28492921
TI  - Interim Safety Data Comparing Ranibizumab With Panretinal Photocoagulation Among
      Participants With Proliferative Diabetic Retinopathy.

PMID- 28492922
TI  - Text Messaging and Protected Health Information: What Is Permitted?

PMID- 28492923
TI  - Sex- and Age-Adjusted Population Analysis of Prevalence Estimates for
      Hidradenitis Suppurativa in the United States.
AB  - Importance: The true prevalence of hidradenitis suppurativa (HS) is unknown.
      Objective: To establish standardized overall and group-specific prevalence
      estimates for HS in the United States. Design, Setting, and Participants: This
      retrospective analysis included a demographically heterogeneous population-based
      sample of more than 48 million unique patients across all US census regions. As
      of October 27, 2016, a total of 47 690 patients with HS were identified using
      electronic health record data. Main Outcomes and Measures: Standardized overall
      point prevalence for HS and sex-, age-, and race-specific prevalence estimates of
      HS in the general US population. Results: Of the 47 690 patients with HS (26.2%
      men and 73.8% women), the overall HS prevalence in the US population sample was
      0.10%, or 98 per 100 000 persons (95% CI, 97-99 per 100 000 persons). The
      adjusted prevalence in women was 137 per 100 000 (95% CI, 136-139 per 100 000),
      more than twice that of men (58 per 100 000; 95% CI, 57-59 per 100 000; P <
      .001). The prevalence of HS was highest among patients aged 30 to 39 years (172
      per 100 000; 95% CI, 169-275 per 100 000) compared with all other age groups
      (range, 15-150 per 100 000; P < .001). Adjusted HS prevalences among African
      American (296 per 100 000; 95% CI, 291-300 per 100 000) and biracial (218 per 100
      000; 95% CI, 202-235 per 100 000) patients were more than 3-fold and 2-fold
      greater, respectively, than that among white patients (95 per 100 000; 95% CI, 94
      96 per 100 000; P < .001). Conclusions and Relevance: Hidradenitis suppurativa is
      an uncommon, but not rare, disease in the United States that disproportionately
      affects female patients, young adults, and African American and biracial
      patients.

PMID- 28492925
TI  - Mental Health Outcomes After Having or Being Denied an Abortion.

PMID- 28492924
TI  - Handheld Reflectance Confocal Microscopy for the Detection of Recurrent
      Extramammary Paget Disease.
AB  - Importance: Extramammary Paget disease (EMPD) is commonly refractory to surgical
      and nonsurgical therapies. Identifying recurrent or persistent EMPD is
      challenging because the disease is multifocal, and multiple blind scouting
      biopsies are usually performed in this setting. Handheld reflectance confocal
      microscopy (HRCM) has been used to diagnose and map primary EMPD and therefore
      may be used to identify EMPD recurrences. Objective: To evaluate HRCM's
      diagnostic accuracy in the setting of recurrent or persistent EMPD as well as its
      potential diagnostic pitfalls. Design, Setting, and Participants: This
      prospective case series study included patients referred to the Dermatology
      Service at Memorial Sloan Kettering Cancer Center between January 1, 2014, and
      December 31, 2016, with biopsy-proven EMPD in whom HRCM was used to monitor
      treatment response. Five patients were included, and 22 sites clinically
      concerning for recurrent or persistent disease were evaluated using HRCM and
      histopathologic examination. In 2 patients, video mosaics were created to
      evaluate large areas. Main Outcomes and Measures: Sensitivity and specificity of
      HRCM in identifying recurrent or persistent EMPD; causes for false-negative
      results according to their location, histopathologic findings, and previous
      treatments. Results: Of the 22 clinically suspicious sites evaluated in 5
      patients (4 men, 1 woman; median [range] age, 70 [56-77] years), 9 (40.9%) were
      positive for recurrent disease on HRCM and histopathologically confirmed, and 13
      (59.1%) sites were negative on HRCM, but 3 of the 13 were positive for EMPD on
      histopathological examination. In general, HRCM had a sensitivity of 75% and a
      specificity of 100% in identifying recurrent or persistent EMPD. False-negative
      results were found in 2 patients and occurred at the margins of EMPD, close to
      previous biopsy sites. Creating video mosaics (or video mosaicking) seemed to
      improve the detection of EMPD. Conclusions and Relevance: Handheld reflectance
      confocal microscopy is a useful auxiliary tool for diagnosing EMPD recurrences
      and can be used to guide scouting biopsies, thus reducing the number of biopsies
      needed to render a correct diagnosis.

PMID- 28492926
TI  - Mental Health Outcomes After Having or Being Denied an Abortion.

PMID- 28492927
TI  - Prevalence of Auditory Problems in Children With Feeding and Swallowing
      Disorders.
AB  - Purpose: Although an interdisciplinary approach is recommended for assessment and
      management of feeding or swallowing difficulties, audiologists are not always
      included in the interdisciplinary team. The purpose of this study is to report
      the prevalence of middle ear and hearing problems in children with feeding and
      swallowing disorders and to compare this prevalence with that in typical
      children. Method: A total of 103 children were included in the study: 44 children
      with feeding and swallowing disorders and 59 children without any such disorders.
      Audiological examinations included case-history information, visualization of the
      ear canals through otoscopy, middle ear evaluation through tympanometry, and
      hearing screenings using an audiometer. Results: The odds of excessive cerumen (p
      = .0000, small effect size), middle ear dysfunction (p = .0148, small effect
      size), and hearing screening failure (p = .0000, large effect size) were 22.14%,
      2.97%, and 13.5% higher, respectively, in children with feeding and swallowing
      disorders compared with typically developing children. Conclusion: The
      significantly higher prevalence of hearing problems in children with feeding and
      swallowing disorders compared with typically developing children suggests that
      inclusion of an audiologist on the interdisciplinary team is likely to improve
      overall interventional outcomes for children with feeding and swallowing
      disorders.

PMID- 28492928
TI  - Local Changes to the Distal Femoral Growth Plate Following Injury in Mice.

PMID- 28492929
TI  - Hepatitis C Virus Infection Among Reproductive-Aged Women and Children in the
      United States, 2006 to 2014.
AB  - Background: In the United States, hepatitis C virus (HCV) infection has increased
      among young persons who inject drugs, but the extent of this epidemic among
      reproductive-aged women and their children is unknown. Objective: To estimate
      numbers and describe characteristics of reproductive-aged women with HCV
      infection and of their offspring. Design: Analysis of the National Notifiable
      Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics
      Health Trends national database from 2011 to 2014. Setting: United States.
      Participants: 171 801 women (aged 15 to 44 years) and 1859 children (aged 2 to 13
      years) with HCV infection reported to the NNDSS; 2.1 million reproductive-aged
      women and 56 684 children who had HCV testing by Quest Diagnostics. Measurements:
      NNDSS HCV case reports and Quest laboratory data regarding unique reproductive
      aged women and children who were tested for HCV infection. Results: The number of
      reproductive-aged women with acute and past or present HCV infection in the NNDSS
      doubled, from 15 550 in 2006 to 31 039 in 2014. Of 581 255 pregnant women tested
      by Quest from 2011 to 2014, 4232 (0.73% [95% CI, 0.71% to 0.75%]) had HCV
      infection. Of children tested by Quest, 0.76% (CI, 0.69% to 0.83%) had HCV
      infection, but the percentage was 3.2-fold higher among children aged 2 to 3
      years (1.62% [CI, 1.34% to 1.96%]) than those aged 12 to 13 years (0.50% [CI,
      0.41% to 0.62%]). Applying the Quest HCV infection rate to annual live births
      from 2011 to 2014 resulted in an estimated average of 29 000 women (CI, 27 400 to
      30 900 women) with HCV infection, who gave birth to 1700 infants (CI, 1200 to
      2200 infants) with the infection each year. Limitations: Only a fraction of HCV
      infections is detected and reported to the NNDSS. Quest data are potentially
      biased, because women who are asymptomatic, do not access health care, or have
      unreported risks may be less likely to be tested for HCV infection. Conclusion:
      These data suggest a recent increase in HCV infection among reproductive-aged
      women and may inform deliberations regarding a role for routine HCV screening
      during pregnancy. Primary Funding Source: Centers for Disease Control and
      Prevention.

PMID- 28492930
TI  - Hearing From the Silent Epidemic.

PMID- 28492931
TI  - The Controversial Epidemiology of Left Ventricular Dysfunction in Patients With
      Myotonic Dystrophy Type 1-Reply.

PMID- 28492933
TI  - Myocardial Fibrosis in Duchenne and Becker Muscular Dystrophy-Reply.

PMID- 28492932
TI  - Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults:
      Mayo Clinic Study of Aging.
AB  - Importance: The prevalence of cerebral cavernous malformation (CCM) is unknown.
      Case ascertainment in most previous studies was based on autopsy data or clinical
      convenience samples, often without detailed clinical or radiologic information.
      Objective: To determine the prevalence of CCM in a population-based sample of
      older adults. Design, Setting, and Participants: This prospective imaging study
      included 4721 participants aged 50 to 89 years who were enrolled between January
      1, 2004, and December 15, 2015, in the Mayo Clinic Study of Aging, a
      longitudinal, population-based study of residents of Olmsted County, Minnesota.
      An age- and sex-stratified sampling strategy was used to randomly select
      participants from Olmsted County using the medical records linkage system of the
      Rochester Epidemiology Project. Participants were invited to undergo brain
      magnetic resonance imaging (MRI). Of the 4721 participants, 2715 had an evaluable
      MRI. All images were reviewed by a board-certified neuroradiologist, and MRI
      reports were searched for the terms cavernous malformation, cavernous angioma,
      and cavernoma. Two vascular neurologists reviewed MRIs, and potential CCMs were
      classified using Zabramski classification. Medical records of the identified
      individuals with CCM were reviewed along with their demographic information,
      medical history, and any symptoms referable to the identified CCM lesion. Main
      Outcomes and Measures: Prevalence of CCM and clinical and radiologic
      characteristics of study participants with CCM. Results: Of the 2715 participants
      who underwent MRI scans, 12 (0.44%) had CCM. With the use of inverse probability
      weights to adjust for participation bias, the overall prevalence was 0.46% (95%
      CI, 0.05-0.86). The age-adjusted prevalence was found to be 0.61% (95% CI, 0
      1.47) for the 50- to 59-year age group, 0.17% (95% CI, 0-0.50) for the 60- to 69
      year age group, 0.45% (95% CI, 0.09-0.81) for the 70- to 79-year age group, and
      0.58% (95% CI, 0-1.29) for the 80- to 89-year age group. The sex-adjusted
      prevalence was 0.41% (95% CI, 0-1.00) for women and 0.51% (95% CI, 0-1.07) for
      men. Observed frequencies were similar in men and women, with a slight male
      predominance. Of the 12 participants with CCM, 9 (75%) had a single Zabramski
      type 2 lesion in a supratentorial location. Only 1 participant (0.037%) was
      symptomatic from the CCM during the study period. Conclusions and Relevance: The
      findings and data from this study are important for determining the potential
      number of patients available for cohort studies and anticipated clinical trials
      in older patients with CCM.

PMID- 28492934
TI  - Mohs Micrographic Surgery Use in the United States Based on Medicare Data-Reply.

PMID- 28492936
TI  - Nonsurgical Rhinoplasty.

PMID- 28492935
TI  - Employer Reactions to Adductor Spasmodic Dysphonia: Exploring the Influence of
      Symptom Severity and Disclosure of Diagnosis During a Simulated Telephone
      Interview.
AB  - Purpose: The purpose of this study was to determine the influence of symptom
      severity and disclosure of adductor spasmodic dysphonia (ADSD) on the perceptions
      of human resource personnel members (HRPs) during a simulated phone interview.
      Method: One female speaker with ADSD was recorded reading an interview script at
      two time points: (a) pre-BOTOX injection (severe), and (b) post-BOTOX injection
      (mild). Thirty-two HRPs evaluated the recording in one of the two conditions via
      a qualitative structured interview. HRPs gave their recommendations regarding
      when and how to disclose ADSD. Results: In the mild condition, no HRP perceived
      that the applicant had a voice disorder. Disclosure was not recommended as often,
      as an impairment was not initially noticed. However, 15/16 HRPs commented on the
      applicant's voice in the severe condition, with most suspecting she was a smoker
      or had lung/throat cancer. Disclosure in the severe condition was recommended
      more often, as it clarified symptoms that were noted at the outset. Conclusions:
      Symptom severity in ADSD influences employer perceptions during the phone
      interview process. Incorrect assumptions may be made about applicants with severe
      symptoms, and apparentness of symptoms influences whether or not disclosure is
      recommended. Results have implications for counseling individuals with ADSD who
      are navigating the job interview process.

PMID- 28492937
TI  - Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder
      and Risk of Motor Vehicle Crashes.
AB  - Importance: Motor vehicle crashes (MVCs) are a major public health problem.
      Research has demonstrated that individuals with attention-deficit/hyperactivity
      disorder (ADHD) are more likely to experience MVCs, but the effect of ADHD
      medication treatment on the risk of MVCs remains unclear. Objective: To explore
      associations between ADHD medication use and risk of MVCs in a large cohort of
      patients with ADHD. Design, Setting, and Participants: For this study, a US
      national cohort of patients with ADHD (n = 2 319 450) was identified from
      commercial health insurance claims between January 1, 2005, and December 31,
      2014, and followed up for emergency department visits for MVCs. The study used
      within-individual analyses to compare the risk of MVCs during months in which
      patients received ADHD medication with the risk of MVCs during months in which
      they did not receive ADHD medication. Exposures: Dispensed prescription of ADHD
      medications. Main Outcomes and Measures: Emergency department visits for MVCs.
      Results: Among 2 319 450 patients identified with ADHD, the mean (SD) age was
      32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male
      patients with ADHD had a 38% (odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of
      MVCs in months when receiving ADHD medication compared with months when not
      receiving medication, and female patients had a 42% (odds ratio, 0.58; 95% CI,
      0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar
      reductions were found across all age groups, across multiple sensitivity
      analyses, and when considering the long-term association between ADHD medication
      use and MVCs. Estimates of the population-attributable fraction suggested that up
      to 22.1% of the MVCs in patients with ADHD could have been avoided if they had
      received medication during the entire follow-up. Conclusions and Relevance: Among
      patients with ADHD, rates of MVCs were lower during periods when they received
      ADHD medication. Considering the high prevalence of ADHD and its association with
      MVCs, these findings warrant attention to this prevalent and preventable cause of
      mortality and morbidity.

PMID- 28492939
TI  - Treatment of Macular Edema Due to Central Retinal Vein Occlusion: Another Score
      for Repackaged Bevacizumab.

PMID- 28492938
TI  - Association Between Breast Milk Bacterial Communities and Establishment and
      Development of the Infant Gut Microbiome.
AB  - Importance: Establishment of the infant microbiome has lifelong implications on
      health and immunity. Gut microbiota of breastfed compared with nonbreastfed
      individuals differ during infancy as well as into adulthood. Breast milk contains
      a diverse population of bacteria, but little is known about the vertical transfer
      of bacteria from mother to infant by breastfeeding. Objective: To determine the
      association between the maternal breast milk and areolar skin and infant gut
      bacterial communities. Design, Setting, and Participants: In a prospective,
      longitudinal study, bacterial composition was identified with sequencing of the
      16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of
      107 healthy mother-infant pairs. The study was conducted in Los Angeles,
      California, and St Petersburg, Florida, between January 1, 2010, and February 28,
      2015. Exposures: Amount and duration of daily breastfeeding and timing of solid
      food introduction. Main Outcomes and Measures: Bacterial composition in maternal
      breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal
      RNA gene. Results: In the 107 healthy mother and infant pairs (median age at the
      time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the
      infants were male. Bacterial communities were distinct in milk, areolar skin, and
      stool, differing in both composition and diversity. The infant gut microbial
      communities were more closely related to an infant's mother's milk and skin
      compared with a random mother (mean difference in Bray-Curtis distances, 0.012
      and 0.014, respectively; P < .001 for both). Source tracking analysis was used to
      estimate the contribution of the breast milk and areolar skin microbiomes to the
      infant gut microbiome. During the first 30 days of life, infants who breastfed to
      obtain 75% or more of their daily milk intake received a mean (SD) of 27.7%
      (15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin.
      Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition
      changes were associated with the proportion of daily breast milk intake in a dose
      dependent manner, even after the introduction of solid foods. Conclusions and
      Relevance: The results of this study indicate that bacteria in mother's breast
      milk seed the infant gut, underscoring the importance of breastfeeding in the
      development of the infant gut microbiome.

PMID- 28492949
TI  - The Role of Skin Care in Optimizing Treatment of Acne and Rosacea.
AB  - A triad approach to the treatment of acne and rosacea has been recommended. This
      integrated management approach includes patient education, selection of
      therapeutic agents, and initiation of an appropriate skin care regime. Proper
      skin care in patients undergoing treatment of both acne and rosacea includes use
      of products formulated for sensitive skin that cleanse, moisturize and
      photoprotect the skin. Both acne and rosacea are associated with epidermal
      barrier dysfunction, which can be mitigated by suitable skin care practices.
      Appropriate skin care recommendations for patients with acne and rosacea will be
      discussed.

PMID- 28492950
TI  - Psychoactive constituents of cannabis and their clinical implications: a
      systematic review.
AB  - Objective This systematic review aims to summarize current evidence on which
      naturally present cannabinoids contribute to cannabis psychoactivity, considering
      their reported concentrations and pharmacodynamics in humans. Design Following
      PRISMA guidelines, papers published before March 2016 in Medline, Scopus
      Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a
      priori selection criteria have been included. Results In 40 original papers,
      three naturally present cannabinoids (?-9-Tetrahydrocannabinol, ?-8
      Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had
      clinical relevance. Of these, the metabolite produces the greatest psychoactive
      effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on
      cannabis psychoactive effects. The proportion of 9-THC in plant material is
      higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports
      vary due to differences in methodological aspects (doses, administration route
      and volunteers' previous experience with cannabis). Conclusions Findings reveal
      that 9-THC contributes the most to cannabis psychoactivity. Due to lower
      psychoactive potency and smaller proportions in plant material, other
      psychoactive cannabinoids have a weak influence on cannabis final effects.
      Current lack of standard methodology hinders homogenized research on cannabis
      health effects. Working on a standard cannabis unit considering 9-THC is
      recommended.

PMID- 28492951
TI  - Information and Communications Technologies (ICT): Problematic use of Internet,
      video games, mobile phones, instant messaging and social networks using MULTICAGE
      TIC.
AB  - Use/abuse of Information and Communications Technologies (ICT) has in recent
      years become a topic of great interest. Current discussion addresses whether it
      must be considered addictive behaviour and if it is a problem that primarily
      affects adolescents and youth. This study aims to understand the problems that
      affect people of all ages in controlling the use of these ICTs and whether they
      are related to mental health problems, stress and difficulties in executive
      control of behaviour. A survey was administered through social networks and
      email, using the MULTICAGE-ICT, a questionnaire that explores problems in the use
      of Internet, mobile phones, video games, instant messaging and social networks.
      Additionally, the Prefrontal Symptom Inventory, General Health Questionnaire and
      Perceived Stress Scale were administered. The sample was comprised of 1,276
      individuals of all ages from different Spanish-speaking countries. The results
      indicate that about 50% of the sample, regardless of age or other variables,
      presents significant problems with the use of these technologies, and that these
      problems are directly related to symptoms of poor prefrontal functioning, stress
      and mental health problems. The results reveal the need for reconsidering whether
      we are facing an addictive behaviour or a new problem demanding environmental,
      psychological, sociological and sociopolitical explanations; therefore, it is
      necessary to reformulate actions to be implemented to address and refocus our
      understanding of the problem.

PMID- 28492952
TI  - Brief Sensation Seeking Scale: Latent structure of 8-item and 4-item versions in
      Peruvian adolescents.
AB  - This research intended to validate two brief scales of sensations seeking with
      Peruvian adolescents: the eight item scale (BSSS8; Hoyle, Stephenson, Palmgreen,
      Lorch, y Donohew, 2002) and the four item scale (BSSS4; Stephenson, Hoyle,
      Slater, y Palmgreen, 2003). Questionnaires were administered to 618 voluntary
      participants, with an average age of 13.6 years, from different levels of high
      school, state and private school in a district in the south of Lima. It analyzed
      the internal structure of both short versions using three models: a)
      unidimensional (M1), b) oblique or related dimensions (M2), and c) the bifactor
      model (M3). Results show that both instruments have a single dimension which best
      represents the variability of the items; a fact that can be explained both by the
      complexity of the concept and by the small number of items representing each
      factor, which is more noticeable in the BSSS4. Reliability is within levels found
      by previous studies: alpha: .745 = BSSS8 and BSSS4 =. 643; omega coefficient:
      .747 in BSSS8 and .651 in BSSS4. These are considered suitable for the type of
      instruments studied. Based on the correlation between the two instruments, it was
      found that there are satisfactory levels of equivalence between the BSSS8 and
      BSSS4. However, it is recommended that the BSSS4 is mainly used for research and
      for the purpose of describing populations.

PMID- 28492953
TI  - Muscle dysmorphia: detection of the use-abuse of anabolic adrogenic steroids in a
      Spanish sample.
AB  - Due to a distortion in the body image, the people who suffer from muscle
      dysmorphia have the self-perception of being less muscular than they currently
      are. With the aim of increasing their muscular development, they resort to the
      use of AAS. The purpose of the present study is to know the prevalence of the use
      of AAS in a Spanish sample affected by muscle dysmorphia. 562 male and 172 female
      bodybuilders and weightlifters were provided with different questionnaires in
      order to know, firstly, if they suffered from this disorder and, secondly, the
      percentage of the participants affected who use these substances. Decision trees
      and regression was applied to create explanatory models for muscle dysmorphia (R
      = 0.78 and R2 = 0.62). The results show that almost 50% of the participants, male
      and female, affected by this disorder use this kind of drugs.

PMID- 28492954
TI  - Design and validation of a Cannabis Use Intention Questionnaire (CUIQ) for
      adolescents.
AB  - In Spain, one in four 14 to 18-year-old adolescents has used cannabis during the
      last twelve months. Demand for treatment has increased in European countries.
      These facts have prompted the development of preventive interventions that
      require screening tools in order to identify the vulnerable population and to
      properly asses the efficacy of such interventions. The Theory of Planned
      Behaviour (TPB), widely used to forecast behavioural intention, has also
      demonstrated a good predictive capacity in addictions. The aim of this study is
      to design and validate a Cannabis Use Intention Questionnaire (CUIQ) based on
      TPB. 1,011 teenagers answered a set of tests to assess attitude towards use,
      subjective norms, self-efficacy towards non-use, and intention to use cannabis.
      CUIQ had good psychometric properties. Structural Equation Modelling results
      confirm the predictive model on intention to use cannabis in the Spanish
      adolescent sample, classified as users and non-users, explaining 40% of variance
      of intention to consume. CUIQ is aimed at providing a better understanding of the
      psychological processes that lead to cannabis use and allowing the evaluation of
      programmes. This can be particularly useful for improving the design and
      implementation of selective prevention programmes.

PMID- 28492955
TI  - The association of Self-concept with Substance Abuse and Problematic Use of Video
      Games in University Students: A Structural Equation Model.
AB  - This study aims to define and contrast an explanatory model of consumption of
      alcohol, tobacco consumption, and problematic use of video games based on self
      concept and its dimensions in a sample of university students. The research was
      conducted with a sample of 490 students from the province of Granada (Spain),
      aged between 20 and 29 years (M = 22.80 +/- 3.63), with a homogeneous
      distribution by gender. The instruments used were the Self-concept Form-5
      Questionnaire (Garcia & Musitu, 1999), the Alcohol Use Disorders Identification
      Test (Saunders, Aasland, Babor, De la Fuente, & Grant, 1993), the Fagerstrom Test
      for Nicotine Dependence (Heatherton, Kozlowski, Frecker, & Fagerstrom, 1991) and
      the Questionnaire for Experiences Related to Video Games (Chamarro et al., 2014).
      A model of structural equations was estimated, which was adjusted properly,
      chi2(8) = 19.843, p = .011; CFI = .963, NFI = .943, IFI = .965, RMSEA = .055. As
      main results, a positive relationship between social and physical self-concept
      and consumption of alcohol was obtained, as well as a negative relationship
      between social self-concept and problematic use of videogames. Academic dimension
      was negatively related to alcohol and video game use. Furthermore, alcohol
      consumption was positively related to tobacco consumption and use of video games.
      It is concluded that levels of self-concept may represent a risk factor in
      substance abuse and digital leisure, and their study and consideration are
      appropriate.

PMID- 28492956
TI  - Relationship between the rs1414334 C/G polymorphism in the HTR2C gene and smoking
      in patients treated with atypical antipsychotics.
AB  - An association has been found between the C allele of the rs1414334 polymorphism
      in the HTR2C gene and the metabolic syndrome in psychiatric patients. However, no
      study has yet evaluated whether this allele is associated with smoking. To assess
      this issue, therefore, we performed a cross-sectional study with a sample of 166
      adult patients treated with atypical antipsychotics in 2012-2013 in a region of
      Spain. The primary variable was the presence of the C allele of the rs1414334
      polymorphism in the HTR2C gene. Secondary variables were the number of pack-years
      (number of cigarettes per day x number of smoking years / 20), age, gender,
      schizophrenia, years since diagnosis, metabolic syndrome criteria and SCORE. A
      stepwise binary logistic regression model was constructed to determine
      associations between primary and secondary variables and their area under the ROC
      curve (AUC) was calculated. Of the total sample, 33 patients (19.9%) had the C
      allele of the polymorphism analyzed. Mean cigarette consumption was 11.6 pack
      years. The multivariate analysis showed the following factors as associated with
      the polymorphism: higher cigarette consumption, being a woman, and not having
      abdominal obesity. The AUC was 0.706. An association was found between increased
      cigarette consumption over the years and the presence of the C allele of the
      rs1414334 polymorphism in the HTR2C gene.

PMID- 28492957
TI  - Screening of alcohol use disorders in psychiatric outpatients: influence of
      gender, age, and psychiatric diagnosis.
AB  - Alcohol use disorders (AUD) are 2 times higher among psychiatric patients than in
      the general population. The under-recognition of this dual diagnosis can entail
      several negative outcomes. Early assessment with a screening tool like the CAGE
      questionnaire could be an opportunity to improve patients' prognoses. The
      objective of this study is to assess AUD risk in an outpatient psychiatric sample
      with a modified CAGE, considering the influence of age, gender and clinical
      psychiatric diagnosis. An observational, multicentric, descriptive study was
      carried out. The 4-item CAGE scale, camouflaged in a healthy lifestyle
      questionnaire, was implemented, using a cut-off point of one. 559 outpatients
      were assessed. 54% were female and the average age was 50.07 years. 182 patients
      presented a CAGE score >=1 (45.1% of men and 21.9% of women). Gender was the
      strongest predictor of a positive result in CAGE, as men were 3.03 times more
      likely to score >=1 on the CAGE questionnaire (p < .001, 95% CI: 0.22-0.49).
      Patients with bipolar and personality disorders had the highest rates of CAGE
      scores >=1 (45.2 and 44.9%, respectively), with a significant association between
      diagnosis and a positive score (p = .002). Patients above 60 years were 2.5 times
      less likely to score >=1 on the CAGE (p = .017, 95% CI: 0.19-0.85). Specific
      screening questionnaires, like the CAGE scale, can be an easy and useful tool in
      the assessment of AUD risk in psychiatric outpatients. Male patients with a
      bipolar or personality disorder present a higher risk of AUD.

PMID- 28492958
TI  - Psychometric validation of the POSIT for screening alcohol and other drugs risk
      consumption among adolescents.
AB  - Early detection of alcohol and drug abuse among adolescents is decisive not only
      for rapid referral and intervention in cases of risk, but also as an indicator
      for use in the evaluation of prevention programs and public policies to reduce
      consumption. One of the most widely-used screening instruments in the world is
      the Problem Oriented Screening Instrument for Teenagers (POSIT) (Rahdert, 1991),
      whose substance use and abuse subscale (POSITUAS) is a brief tool of enormous
      applied potential. However, there is still no empirical validation study that
      would ensure its good psychometric performance in Spain. The aim of this paper is
      to analyse the psychometric properties of POSITUAS among Spanish adolescents. For
      this purpose, 569 students aged between 12 and 18 years (M = 14.71; SD = 1.79)
      were personally interviewed. The study sample was selected through two-stage
      sampling. The results obtained, using the Adolescent Diagnostic Interview
      (Winters & Henly, 1993) as the gold criterion, allow us to inform that the
      Spanish version of the POSITUAS has excellent psychometric behaviour, both at the
      level of internal consistency (a  = .82) as well as regards sensitivity (94.3%)
      and specificity (83.9%), with an area under the ROC curve of .953. Also, the
      realisation of a Confirmatory Factor Analysis allows for verifying the one
      dimensional character of the scale. As a result, POSITUAS is made available to
      researchers and professionals in the field of addictive behaviours for use with a
      minimum of psychometric guarantees.

PMID- 28492959
TI  - The relationship between consumption of alcohol and other drugs and problematic
      Internet use among adolescents.
AB  - Alcohol and drug use among adolescents has been causing great concern for decades
      in Spain and in the European Union as a whole. In addition, the technology boom
      experienced over the last two decades has contributed to the emergence of a new
      public healthcare issue: problematic Internet use. The increasing importance that
      both problems have been gaining in recent years has led some authors to analyze
      the relationship between alcohol and the consumption of other drugs alongside
      problematic Internet use, and to provide relevant empirical evidence. Based on a
      sample of 3,882 Spanish adolescents aged between 12 and 18, the results obtained
      confirm that there is a relationship between the consumption of alcohol (measured
      by the AUDIT) and other drugs (measured by the CRAFFT and the CAST), and
      problematic Internet use (measured by the EUPI-a). Problematic Internet users
      among them not only have more significant levels of substance use, but also a
      three-times greater chance of developing hazardous drug use (39.4% vs 13.3%).
      This highlights the need to develop transversal prevention capable of acting on
      the common variables to both issues, beyond developing programs focused on
      specific behaviors. In this sense, values-based education and life skills
      training should be given priority in prevention.

PMID- 28492961
TI  - Chemsex. An emergent phenomenon.
AB  - Letter to the editor.

PMID- 28492960
TI  - Dual diagnosis in Depression: treatment recommendations.
AB  - Comorbidity between substance use disorders (SUD) and major depression (MD) is
      the most common dual pathology in the field of addiction to substances and has
      prevalence rates ranging between 12% and 80%, which complicates the response to
      treatment and worsens the prognosis of patients. Differentiating between
      diagnoses of induced depressive episodes and primary depressive episodes
      concurrent to substance use is especially relevant for therapeutic management.
      This article presents the state of the art of the currently available
      pharmacologic treatments of comorbid depression in patients with SUD, taking into
      account the safety and risk of abuse of antidepressant drugs. Due to the fact
      that comorbidity of MD and SUD is frequent and presents greater
      psychopathological and medical severity, as well as worse social functioning, it
      is crucial to treat MD and SUD simultaneously using the integrated treatment
      model and not to treat both conditions separately.

PMID- 28492962
TI  - Self-quitting in a Spanish sample. An exploratory study.
AB  - Letter to the editor.

PMID- 28492963
TI  - Assessing the decision-making capacity of the addicted population to take part in
      research: myths, barriers, and benefits.
AB  - Letter to the editor.

PMID- 28492964
TI  - Studies into severe famine in early life and diabetes in adulthood: the need to
      control for differences in participant age and location.

PMID- 28492965
TI  - Role of ICG-99mTc-nanocolloid for sentinel lymph node detection in cervical
      cancer: a pilot study.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early
      cervical cancer. For this purpose, the tracers most commonly used are
      radiotracers based on technetium. For the last decade, indocyanine green (ICG)
      has been used as a tracer for SLNB in other malignancies with excellent results
      and, more recently, a combination of ICG and a radiotracer has been shown to have
      the advantages of both tracers. The aim of this study was to evaluate the role of
      ICG-99mTc-nanocolloid in SLN detection in patients with cervical cancer. METHODS:
      This prospective study included 16 patients with cervical cancer. The hybrid
      tracer was injected the day (19-21 h) before surgery for planar and SPECT/CT
      lymphoscintigraphy. Blue dye was administered periorificially in 14 patients.
      SLNs were removed according to their distribution on lymphoscintigraphy and when
      radioactive, fluorescent and/or stained with blue dye. Nodal specimens were
      pathologically analysed for metastases including by immunochemistry. RESULTS:
      Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69
      SLNs were removed, of which 66 were detected by their radioactivity signal and 67
      by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14
      patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases
      were diagnosed in two patients, and were the only lymphatic nodes involved.
      CONCLUSIONS: SLNB with ICG-99mTc-nanocolloid is feasible and safe in patients
      with early cervical cancer. This hybrid tracer provided bilateral SLN detection
      in all patients and a higher detection rate than blue dye, so it could become an
      alternative to the combined technique.

PMID- 28492966
TI  - Complex Genes Are Preferentially Retained After Whole-Genome Duplication in
      Teleost Fish.
AB  - Gene duplication generates new genetic material which, if retained after
      duplication, may contribute to organismal evolution. A whole-genome duplication
      occurred in the ancestry of teleost fish and consequently there are many
      duplicated genes in teleost genomes. Indeed, it has been proposed that the
      evolutionary diversification of teleost fish may have been stimulated by the fish
      specific genome duplication (FSGD). However, it is not clear which factors
      determine which genes are retained as duplicate copies and which return to a
      singleton state after duplication. In the present study, gene complexity, in
      terms of encoded protein length and functional domain number, is compared between
      duplicate and singleton genes for nine well-annotated teleost genomes. A total of
      933 gene families with retained duplicates and 4590 singleton gene families are
      analysed. Genes with retained duplicates are found to be significantly longer
      (27.9-38.2%) and to have more functional domains (20.5-26.5%) than singleton
      genes in all the nine teleost genomes, suggesting that genes encoded longer
      proteins with and more functional domains were preferentially retained after
      whole-genome duplication in teleosts. This differential retention of duplicated
      genes will have increased the genomic complexity of teleost fish after FSGD
      which, together with differential duplicated gene retention as a lineage
      splitting force, may have greatly contributed to the successful diversification
      of teleost fish.

PMID- 28492967
TI  - A Test for Gene Flow among Sympatric and Allopatric Hawaiian Picture-Winged
      Drosophila.
AB  - The Hawaiian Drosophila are one of the most species-rich endemic groups in Hawaii
      and a spectacular example of adaptive radiation. Drosophila silvestris and D.
      heteroneura are two closely related picture-winged Drosophila species that occur
      sympatrically on Hawaii Island and are known to hybridize in nature, yet exhibit
      highly divergent behavioral and morphological traits driven largely through
      sexual selection. Their closest-related allopatric species, D. planitibia from
      Maui, exhibits hybrid male sterility and reduced behavioral reproductive
      isolation when crossed experimentally with D. silvestris or D. heteroneura. A
      modified four-taxon test for gene flow was applied to recently obtained genomes
      of the three Hawaiian Drosophila species. The analysis indicates recent gene flow
      in sympatry, but also, although less extensive, between allopatric species. This
      study underscores the prevalence of gene flow, even in taxonomic groups
      considered classic examples of allopatric speciation on islands. The potential
      confounding effects of gene flow in phylogenetic and population genetics
      inference are discussed, as well as the implications for conservation.

PMID- 28492968
TI  - [Monitoring methods and their results in environmental medicine - implications
      for medical counsellors].
AB  - Besides effect and environmental monitoring, human biomonitoring (HBM) offers an
      attractive method for analyzing the distribution and intensity of anthropogenic
      environmental pollutants in individuals or in particular groups of the
      population. However, no assessment values of comparable reliability are available
      to enable an interpretation of the results of environmental studies from the
      viewpoint of environmental health. This must be taken into account when reporting
      findings of such studies as well as in medical consultation, in order to avoid
      overdiagnosis and unnecessary anxiety for the participant. In medical practice,
      care should be taken when dealing with monitoring results outside the normal
      range! Environmental or biomonitoring results provide only a part of the
      available information alongside medical history and clinical examinations. In the
      case of tests performed for private interests as well as tests carried out within
      the framework of an epidemiological environmental survey, communication of
      results and findings can be problematic. In epidemiological studies, a close co
      operation between the participant's consultant physician and physicians
      conducting the study is beneficial in order to ensure professional advisory
      counselling for subjects with results outside the normal range.

PMID- 28492969
TI  - ?

PMID- 28492970
TI  - Oral and intravenous steroids for multiple sclerosis relapse: a systematic review
      and meta-analysis.
AB  - Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses,
      but the most desirable route of administration is still matter of debate. The aim
      of the study was to compare the efficacy and safety of oral versus intravenous
      steroids for treatment of acute relapses in patients with MS. Randomized or quasi
      randomized, parallel group trials with direct comparison between oral and
      intravenous steroid treatment in MS patients with acute relapse were identified
      through a systematic literature search. Six trials were included involving 419
      participants, 210 for oral, and 209 for intravenous groups, respectively. The
      weighted mean differences (WMDs) in the Kurtzke's Expanded Disability Status
      Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 [(
      0.09 to 0.73); p = 0.129] and 0.11 [(-0.12 to 0.33); p = 0.355] at 1 and 4 weeks
      after treatment, respectively. The risk ratios (RRs) for improvement by at least
      one EDSS point were 0.79 [(0.37-1.68); p = 0.539] at week 1 and 0.92 (0.76-1.12);
      p = 0.400] at week 4. There were no differences in the relapse rate and relapse
      freedom at 6 months between groups. The WMDs in the mean percentage reduction of
      Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (-0.02,
      0.29); p = 0.083] and 0.04 (-0.19, 0.28); p = 0.705] at 1 and 4 weeks from
      treatment. Among the adverse events, insomnia was significantly associated with
      the oral route of steroid administration [RR 1.25 (1.07-1.46); p = 0.005]. In
      adult patients with acute MS relapse, there were no clear-cut differences in the
      efficacy and overall tolerability between oral and intravenous steroids.

PMID- 28492971
TI  - Current conservation status of Germain's langur (Trachypithecus germaini) in
      Vietnam.
AB  - Following the split of the silvered langurs of Indochina into two species based
      on molecular and phenotypic data, there is a need to reevaluate their
      distribution and update their conservation status. Here, we report the
      distribution and assess the population size of Germain's langur (Trachypithecus
      germaini) within its known range across Vietnam. We confirmed this species at six
      of seven survey sites in different habitats within three provinces in the Mekong
      Delta Region, including semi-evergreen forest at the Seven Mountains of An Giang
      Province, mangrove forest in Ngoc Hien and Nam Can Districts and Melaleuca forest
      in U Minh Ha National Park of Ca Mau Province, and limestone forest at Kien Luong
      Karst Area and semi-evergreen and evergreen forests at Phu Quoc National Park of
      Kien Giang Province. We found no evidence of this species in Mui Ca Mau National
      Park, Ca Mau Province where it was previously reported. We conservatively
      estimate that the total population of Germain's langurs in Vietnam consists of
      362-406 individuals, with the largest population found in the Kien Luong Karst
      Area. Hunting and habitat loss are severely impacting Germain's langur, resulting
      in the extirpation of the population in Mui Ca Mau National Park and small,
      isolated populations in the Seven Mountains and Ngoc Hien and Nam Can Districts.
      However, the ability of this species to inhabit a wide range of forest types, and
      its increasing population sizes in Phu Quoc National Park and Kien Luong Karst
      Area, provide signs of hope that continued conservation actions may help in its
      long-term survival.

PMID- 28492972
TI  - Performance of the pediatric logistic organ dysfunction (PELOD) and (PELOD-2)
      scores in a pediatric intensive care unit of a developing country.
AB  - : The study aimed to compare two scores: the pediatric logistic organ dysfunction
      (PELOD) with its updated version (PELOD-2) in describing the severity of organ
      dysfunction in pediatric intensive care unit (PICU) and assess the performance of
      PELOD-2 in the Egyptian population. A prospective cohort study of 200 patients
      consecutively admitted to PICU between July 2015 and A 2016 was included. The
      median age was 6 months, and the male to female ratio was 1.04. The median length
      of PICU stay was 4 days. The overall predicted number of deaths using PELOD was
      76 patients whereas, by PELOD-2, it was 50 patients. The observed mortality was
      50 patients. The area under the receiving operating characteristic curve was
      excellent for both PELOD and PELOD-2 (0.93 and 0.91, respectively). The Hosmer
      and Lemeshow goodness-of-fit test showed good calibration of PELOD-2 (chi 2 =
      9.9, p = 0.27), while PELOD showed poor calibration (chi 2 = 42, p = 0.000) in
      the same studied group. CONCLUSION: Both scores had excellent discrimination.
      PELOD-2 is reproducible and easier to perform and had better calibration compared
      to PELOD score. What is Known: * Pediatric logistic organ dysfunction (PELOD)
      score was developed 1999 and validated in 2003 to describe the organ dysfunction
      severity in pediatric intensive care units. * A new and easier version of (PELOD
      2) was developed 2013 in France and Belgium to replace the old score. It is
      important to assess the performance of the new score in other population else
      than the original. What is New: In an Egyptian pediatric intensive care, the
      performance of the score revealed: * PELOD-2 was an excellent discriminatory
      score comparable to the original score. * PELOD-2 calibrated well in the Egyptian
      population while the old score had poor calibration.

PMID- 28492973
TI  - Fast therapeutic hypothermia prevents post-cardiac arrest syndrome through
      cyclophilin D-mediated mitochondrial permeability transition inhibition.
AB  - The opening of the mitochondrial permeability transition pore (PTP), which is
      regulated by the matrix protein cyclophilin D (CypD), plays a key role in the
      pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that
      therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated
      PTP inhibition in both heart and brain. In addition, we investigated whether
      specific pharmacological PTP inhibition would confer additive protection to
      cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by
      120 min of reperfusion. Five groups (n = 10-15/group) were studied: control group
      (CA only), hypothermia group (HT, hypothermia at 32-34  degrees C induced by
      external cooling at reperfusion), NIM group (injection at reperfusion of 2.5
      mg/kg NIM811, a specific CypD inhibitor), HT + NIM, and sham group. The following
      measurements were taken: hemodynamics, echocardiography, and cellular damage
      markers (including S100beta protein and troponin Ic). Oxidative phosphorylation
      and PTP opening were assessed on mitochondria isolated from both brain and heart.
      Acetylation of CypD was measured by immunoprecipitation in both the cerebral
      cortex and myocardium. Hypothermia and NIM811 significantly prevented
      cardiovascular dysfunction, pupillary areflexia, and early tissue damage.
      Hypothermia and NIM811 preserved oxidative phosphorylation, limited PTP opening
      in both brain and heart mitochondria and prevented increase in CypD acetylation
      in brain. There were no additive beneficial effects in the combination of NIM811
      and therapeutic hypothermia. In conclusion, therapeutic hypothermia limited post
      CA syndrome by preventing mitochondrial permeability transition mainly through a
      CypD-dependent mechanism.

PMID- 28492974
TI  - Influence of drinking water salinity on carcass characteristics and meat quality
      of Santa Ines lambs.
AB  - This study aimed to evaluate the effects of different salinity levels in drinking
      water on the quantitative and qualitative characteristics of lamb carcass and
      meat. Ram lambs (n = 32) were distributed in a completely randomized design with
      four levels of salinity in the drinking water (640 mg of total dissolved solids
      (TDS)/L of water, 3188 mg TDS/L water, 5740 mg TDS/L water, and 8326 mg TDS/L
      water). After slaughter, blending, gutting, and skinning the carcass, hot and
      biological carcass yields were obtained. Then, the carcasses were cooled at 5 
      degrees C for 24 h, and then, the morphometric measurements and the cold carcass
      yield were determined and the commercial cuts made. In the Longissimus lumborum
      muscle color, water holding capacity, cooking loss, shear force, and chemical
      composition were determined. The yields of hot and cold carcass (46.10 and
      44.90%), as well as losses to cooling (2.40%) were not affected (P > 0.05) by the
      salinity levels in the water ingested by the lambs. The meat shear force was 3.47
      kg/cm2 and moisture, crude protein, ether extract, and ash were 73.62, 22.77,
      2.5, and 4.3%, respectively. It is possible to supply water with salinity levels
      of up to 8326 mg TDS/L, because it did not affect the carcass and meat
      characteristics of Santa Ines lambs.

PMID- 28492975
TI  - Practice makes perfect: familiarity of task determines success in solvable tasks
      for free-ranging dogs (Canis lupus familiaris).
AB  - Domestic dogs' (Canis lupus familiaris) socio-cognitive faculties have made them
      highly sensitive to human social cues. While dogs often excel at understanding
      human communicative gestures, they perform comparatively poorly in problem
      solving and physical reasoning tasks. This difference in their behaviour could be
      due to the lifestyle and intense socialization, where problem solving and
      physical cognition are less important than social cognition. Free-ranging dogs
      live in human-dominated environments, not under human supervision and are less
      socialized. Being scavengers, they often encounter challenges where problem
      solving is required in order to get access to food. We tested Indian street dogs
      in familiar and unfamiliar independent solvable tasks and quantified their
      persistence and dependence on a novel human experimenter, in addition to their
      success in solving a task. Our results indicate that free-ranging dogs succeeded
      and persisted more in the familiar task as compared to the unfamiliar one. They
      showed negligible amount of human dependence in the familiar task, but showed
      prolonged gazing and considerable begging behaviour to the human experimenter in
      the context of the unfamiliar task. Cognitive abilities of free-ranging dogs thus
      play a pivotal role in determining task-associated behaviours based on
      familiarity. In addition to that, these dogs inherently tend to socialize with
      and depend on humans, even if they are strangers. Our results also illustrate
      free-ranging dogs' low competence at physical cognitive tasks.

PMID- 28492976
TI  - Squalene promotes cholesterol homeostasis in macrophage and hepatocyte cells via
      activation of liver X receptor (LXR) alpha and beta.
AB  - OBJECTIVE: To examine the effect of squalene on liver X receptors (LXRs) that
      regulate target genes associated with reverse cholesterol transport and thus
      control whole-body cholesterol homeostasis. RESULTS: To examine the effect of
      squalene on liver X receptors (LXRs) that regulate target genes associated with
      reverse cholesterol transport and thus control whole-body cholesterol
      homeostasis. Squalene significantly stimulated the transactivation of liver X
      receptor modulator LXRalpha and LXRbeta. The mRNA expression of LXRs and their
      target genes, including ABCA1, ABCG1 and ApoE, was significantly induced in
      macrophages stimulated with squalene, resulting in removal of cholesterol from
      the cells. Notably, squalene did not induce higher hepatic triacylglycerol levels
      nor did it alter expression of sterol regulatory element-binding protein 1c
      (SREBP-1c) and FAS in hepatocyte cells, primarily because of its upregulation of
      Insig-2a, which delays nuclear translocation of SREBP-1c, a key hepatic lipogenic
      transcription factor. CONCLUSION: Squalene has hypocholesterolemic effect through
      the activation of LXRalpha and beta without inducing hepatic lipogenesis.

PMID- 28492977
TI  - Chaperone-substrate interactions monitored via a robust TEM-1 beta-lactamase
      fragment complementation assay.
AB  - OBJECTIVE: To investigate the application of the TEM-1 beta-lactamase protein
      fragment complementation assay (PCA) in detecting weak and unstable protein
      protein interactions as typically observed during chaperone-assisted protein
      folding in the periplasm of Escherichia coli. RESULTS: The TEM-1 beta-lactamase
      PCA system effectively captured the interactions of three pairs of chaperones and
      substrates. Moreover, the strength of the interactions can be quantitatively
      analyzed by comparing different levels of penicillin resistance, and the assay
      can be performed under 0.5% butanol, a stress condition thought to be
      physiologically relevant. CONCLUSIONS: The beta-lactamase PCA system faithfully
      reports chaperone-substrate interactions in the bacterial cell envelope, and
      therefore this system has the potential to map the complex protein homeostasis
      network under a fluctuating environment.

PMID- 28492978
TI  - Seizure response to perampanel in drug-resistant epilepsy with gliomas: early
      observations.
AB  - Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a
      shared mechanism of AMPA-activation involving both seizure activity and tumor
      growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE
      in low- and high-grade gliomas. Seizure response was defined as 50% drop in
      seizure frequency or as seizure-freedom. Cognitive function was examined by
      computerized test on cognitive speed (CTCS), which is sensitive to the type of
      cognitive dysfunction associated with epilepsy and use of anticonvulsants.
      Treatment policy included reduction of dose or discontinuation of one or more
      concurrent AEDs, once a seizure-free response was observed. Twelve patients were
      included patients, median age 41 years, 9 men versus 3 women and 6 months median
      duration of follow-up. An objective seizure response (75%) was observed in 9
      (75%) out of 12 patients: 50%-seizure response in 3, seizure-freedom in 6, which
      is plainly more than seen with other types of DRE. Side-effects occurred in six
      patients. Cognitive function as examined by CTCS improved in six out of eight
      associated withlowering of concurrent AEDs. The final median dose of PER was 8 mg
      (varying between 2 and 12 mg). These results of an objective seizure response in
      9 (75%) out of 12 patients treated by PER in DRE may be interpreted as a
      surrogate-marker of tumor response secondary to AMPA blockade, advancing
      confirmation by MR imaging. These results warrant further study of PER on tumor
      activity in gliomas.

PMID- 28492980
TI  - [Haemostatic management in postpartum haemorrhage : Nationwide survey in
      Germany].
AB  - BACKGROUND: In order to ensure evidence-based haemostatic management of
      postpartum haemorrhage (PPH, blood loss >500 ml) consistent with guidelines
      appropriate structural conditions must be fulfilled regardless of different
      levels (1-3) in perinatal care. The aim of the survey was to identify differences
      in haemostatic management in PPH under consideration of the different levels of
      perinatal care in Germany. MATERIALS AND METHODS: An electronic questionnaire
      assessing the structural and therapeutic preconditions for haemostatic management
      was sent to 533 anaesthesiology departments serving obstetric units. RESULTS: A
      total of 156 (29 %) questionnaires returned from hospitals of all levels were
      analysed. PPH occur in all and increase with higher level hospitals (level 1 <5
      PPH/year vs. 3 >30 PPH/year). The percentage of PPH requiring red blood cell
      (RBC) transfusion amounts to <25 % (all levels). A bleeding history (35 %, all
      levels), laboratory coagulation tests (29 %, all levels) as well as viscoelastic
      point-of-care coagulation tests (42 %, mainly level 3) are limited in their
      availability. Blood loss is usually estimated (99 %, all levels), not measured.
      Tranexamic acid (>80 %, all levels), fibrinogen (>60 %, all levels) and fresh
      frozen plasma (FFP) (30 %, level 2a) are first line therapeutics. In level 2b and
      3 FFP is a second line therapeutic. RBC transfusion is indicated at haemoglobin
      <5-7 g/dl (57-69 %, all levels), while 15-29 % in level 3 did not base their
      decision to transfuse RBC on haemoglobin only. CONCLUSIONS: Guideline-consistent
      haemostatic management of PPH is provided in almost all hospitals independent of
      the perinatal care level. Deviances from guidelines (measuring blood loss,
      bleeding history of the patient) affect all levels of perinatal care in Germany.

PMID- 28492979
TI  - Ethnic Identity, Acculturation, and 12-Month Psychiatric Service Utilization
      Among Black and Hispanic Adults in the U.S.
AB  - A cross-sectional study design was used to examine the associations of ethnic
      identity, acculturation, and psychiatric service utilization among Wave 2
      respondents of the National Epidemiologic Survey on Alcohol Related Conditions
      with 12-month psychiatric disorders who self-identified as Black (6587, 19%) and
      Hispanic (6359, 18%). Weighted multivariable regression analyses were conducted
      to examine the relationships between ethnic identity, acculturation, and 12-month
      psychiatric service utilization. Stronger ethnic identity was associated with
      decreased odds of using psychiatric services among Black (AOR = 0.956; CI = 0.923
      0.991) and Hispanic individuals (AOR = 0.967; CI = 0.945-0.990). Greater
      acculturation was associated with an increased odds of psychiatric service
      utilization for Hispanic individuals (AOR = 1.025; CI = 1.000-1.050). These
      findings suggest that a sense of pride, belonging, and attachment to one's
      racial/ethnic group and participating in ethnic behaviors is associated with
      lower rates of participation in psychiatric services; alternatively, acquiring
      key elements of the U.S. culture is associated with greater participation in
      psychiatric services.

PMID- 28492981
TI  - Evidence that Osteocytes in Autogenous Bone Fragments can Repair Disrupted
      Canalicular Networks and Connect with Osteocytes in de novo Formed Bone on the
      Fragment Surface.
AB  - Autogenous bone fragments generated during surgery (e.g. implant site
      preparation) accelerate bone formation by the release of a large variety of
      growth factors from the extracellular matrix and the cells contained within.
      Osteocytes, whether viable or apoptotic, within such fragments are able to
      recruit osteoclasts to a site of bone remodelling. Here, using correlative
      scanning electron microscopy, we provide compelling evidence that at one week
      healing in the Sprague Dawley rat tibia, following surgery (and/or the placement
      of a bone-anchored implant), autogenous bone fragments support bone formation on
      their surface. Furthermore, osteocytes within the autogenous fragments are
      frequently able to repair the disrupted canalicular networks and appear to
      connect with osteocytes (or osteoblastic-osteocytes) in the de novo formed bone
      on the surface of the fragment.

PMID- 28492982
TI  - Adenosine A1 Receptors Play an Important Protective Role Against Cognitive
      Impairment and Long-Term Potentiation Inhibition in a Pentylenetetrazol Mouse
      Model of Epilepsy.
AB  - Epilepsy is a complicated neurological disorder that occurs worldwide and
      features several kinds of comorbidities in addition to recurrent seizures. One of
      the most common comorbidities is cognitive impairment, which seriously affects
      patients' quality of life. Through activating pre- and postsynaptic adenosine A1
      receptors (A1Rs), adenosine has demonstrated anticonvulsant and neuroprotective
      effects in many epileptic animal models. However, whether the neuroprotective
      effect of A1Rs will protect cognition during epileptogenesis remains unknown.
      Therefore, by using A1R knockout (KO) mice and establishing a pentylenetetrazole
      (PTZ)-kindled model of epilepsy, the present study investigated A1Rs' influences
      on memory and synaptic function. Morris water maze test results indicated that
      A1R knockout exacerbated the memory impairment induced by PTZ kindling compared
      with the wild-type group. To further study the synaptic function of epileptic
      A1Rs KO mice, we recorded long-term potentiation (LTP) in the hippocampal CA3-CA1
      pathway, and LTP was highly inhibited in kindled A1R KO mice compared with
      kindled wild-type mice. To reveal the mechanisms underlying these effects,
      neuronal loss, cell apoptosis, and relevant synaptic protein levels in
      hippocampus were assessed. Epileptic A1R KO mice exhibited significant reductions
      in neuronal cell survival in the CA1 region and a marked increase in the
      activation of caspase-3 in the hippocampus compared with epileptic wild-type
      mice. In addition, an obvious decrease in the PSD95 and BDNF expression levels of
      epileptic A1R KO mice was observed 7 days after complete kindling. In conclusion,
      these findings indicated that A1Rs play an important protective role against
      cognitive impairment by reducing neuron loss and increasing BDNF and PSD95
      levels. Activation of A1Rs during epileptogenesis might be beneficial to the
      preservation of epileptic individuals' cognitive functions.

PMID- 28492983
TI  - Target enrichment sequencing in cultivated peanut (Arachis hypogaea L.) using
      probes designed from transcript sequences.
AB  - Enabled by the next generation sequencing, target enrichment sequencing (TES) is
      a powerful method to enrich genomic regions of interest and to identify sequence
      variations. The objective of this study was to explore the feasibility of probe
      design from transcript sequences for TES application in calling sequence variants
      in peanut, an important allotetraploid crop with a large genome size. In this
      study, we applied an in-solution hybridization method to enrich DNA sequences of
      seven peanut genotypes. Our results showed that it is feasible to apply TES with
      probes designed from transcript sequences in polyploid peanut. Using a set of
      31,123 probes, a total of 5131 and 7521 genes were targeted in peanut A and B
      genomes, respectively. For each genotype used in this study, the probe target
      capture regions were efficiently covered with high depth. The average on-target
      rate of sequencing reads was 42.47%, with a significant amount of off-target
      reads coming from genomic regions homologous to target regions. In this study,
      when given predefined genomic regions of interest and the same amount of
      sequencing data, TES provided the highest coverage of target regions when
      compared to whole genome sequencing, RNA sequencing, and genotyping by
      sequencing. Single nucleotide polymorphism (SNP) calling and subsequent
      validation revealed a high validation rate (85.71%) of homozygous SNPs, providing
      valuable markers for peanut genotyping. This study demonstrated the success of
      applying TES for SNP identification in peanut, which shall provide valuable
      suggestions for TES application in other non-model species without a genome
      reference available.

PMID- 28492984
TI  - Comparative transcript profiling of fertile and sterile flower buds from multiple
      allele-inherited male sterility in Chinese cabbage (Brassica campestris L. ssp.
      pekinensis).
AB  - We studied the underlying causes of multiple-allele-inherited male sterility in
      Chinese cabbage (Brassica campestris L. ssp. pekinensis) by identifying
      differentially expressed genes (DEGs) related to pollen sterility between fertile
      and sterile flower buds. In this work, we verified the stages of sterility
      microscopically and then performed transcriptome analysis of mRNA isolated from
      fertile and sterile buds using Illumina HiSeq 2000 platform sequencing.
      Approximately 80% of ~229 million high-quality paired-end reads were uniquely
      mapped to the reference genome. In sterile buds, 699 genes were significantly up
      regulated and 4096 genes were down-regulated. Among the DEGs, 28 pollen cell wall
      related genes, 54 transcription factor genes, 45 phytohormone-related genes, 20
      anther and pollen-related genes, 212 specifically expressed transcripts, and 417
      DEGs located on linkage group A07 were identified. Six transcription factor genes
      BrAMS, BrMS1, BrbHLH089, BrbHLH091, BrAtMYB103, and BrANAC025 were identified as
      putative sterility-related genes. The weak auxin signal that is regulated by
      BrABP1 may be one of the key factors causing pollen sterility observed here.
      Moreover, several significantly enriched GO terms such as "cell wall organization
      or biogenesis" (GO:0071554), "intrinsic to membrane" (GO:0031224), "integral to
      membrane" (GO:0016021), "hydrolase activity, acting on ester bonds" (GO:0016788),
      and one significantly enriched pathway "starch and sucrose metabolism" (ath00500)
      were identified in this work. qRT-PCR, PCR, and in situ hybridization experiments
      validated our RNA-seq transcriptome analysis as accurate and reliable. This study
      will lay the foundation for elucidating the molecular mechanism(s) that underly
      sterility and provide valuable information for studying multiple-allele-inherited
      male sterility in the Chinese cabbage line 'AB01'.

PMID- 28492985
TI  - Catheter ablation of paroxysmal atrial fibrillation: circumferential pulmonary
      vein ablation: success rates with and without exclusion of areas adjacent to the
      esophagus.
AB  - BACKGROUND: Catheter ablation has become the first line of therapy in patients
      with symptomatic, recurrent, drug-refractory paroxysmal atrial fibrillation.
      Circumferential pulmonary vein ablation is still the standard approach in these
      patients. The occurrence of an atrioesophageal fistula is a rare but life
      threatening complication after such ablation procedures. This is due to the fact
      that the esophagus does frequently have a very close anatomical relationship to
      the left or right pulmonary vein ostia. The aim of our study was to evaluate
      whether the exclusion of areas adjacent to the esophagus does have a significant
      effect on the success rate after circumferential pulmonary vein ablation.
      METHODS: Two hundred consecutive patients [121 men, 69 women; mean age 59.1 years
      (SD +/- 11.3 years)] with symptomatic paroxysmal atrial fibrillation underwent a
      circumferential pulmonary vein ablation procedure (using the CARTO- or the NAVX
      system). In 100 patients, a complete circumferential pulmonary vein ablation was
      attempted regardless of the anatomical relationship between the ablation sites
      and the esophagus (group A). In the remaining 100 patients, the esophagus was
      marked by a special EP catheter and areas adjacent to the esophagus were excluded
      from the ablation procedure. After discharge, patients were scheduled for
      repeated visits at the arrhythmia clinic at 1, 3, 6, 9, 12, 24 and 36 months
      after the ablation procedure. RESULTS: The ablation procedure could be performed
      as planned in all 200 patients. In group A, all pulmonary veins could be isolated
      successfully in 88 out of 100 patients (88%). A mean number of 3.9 pulmonary
      veins (SD +/- 0.37 PVs) were isolated per patient. The 12 cases of an incomplete
      pulmonary vein isolation were due to poorly accessible pulmonary vein ostia. In
      group B, all pulmonary veins could be isolated successfully in only 58 out of 100
      patients (58%; P < 0.01). A mean number of 3.5 PVs (SD +/- 0.6 PVs) were isolated
      per patient (P < 0.01). This was mostly due to a close anatomical relationship to
      the esophagus. The ablation strategy had to be modified in 46/100 patients in
      group B because of a close anatomical relationship between the right (n = 25) or
      left (n = 21) pulmonary vein ostia and the esophagus. One year after the ablation
      procedure, 87% of patients in group A (87/100) and 79% of patients in group B
      (79/100) were free from an arrhythmia recurrence (P = 0.19). Three years after
      catheter ablation, the success rate was 80% (no arrhythmia recurrence in 80 out
      of 100 patients) in group A and 66% in group B (no arrhythmia recurrence in 66
      out of 100 patients; P = 0.04). There were no major complications during long
      term follow-up. CONCLUSIONS: The exclusion of areas adjacent to the esophagus
      results in a markedly higher percentage of incompletely isolated pulmonary veins
      after circumferential pulmonary vein ablation procedures. This results in a
      significantly higher arrhythmia recurrence rate during long-term follow-up.

PMID- 28492986
TI  - Biosynthesis and bioactivity of glucosinolates and their production in plant in
      vitro cultures.
AB  - MAIN CONCLUSION: Glucosinolates are biologically active compounds which are
      involved in plant defense reaction. The use of plant in vitro cultures and
      genetic engineering is a promising strategy for their sustainable production.
      Glucosinolates are a class of secondary metabolites found mainly in Brassicaceae,
      which contain nitrogen and sulfur in their structures. Glucosinolates are divided
      into three groups depending on the amino acid from which they are biosynthesized.
      Aliphatic glucosinolates are generally derived from leucine, valine, methionine,
      isoleucine and alanine while indole and aromatic glucosinolates are derived from
      tryptophan and phenylalanine or tyrosine, respectively. These compounds are
      hydrolyzed by the enzyme myrosinase when plants are stressed by biotic and
      abiotic factors, obtaining different degradation products. Glucosinolates and
      their hydrolysis products play an important role in plant defense responses
      against different types of stresses. In addition, these compounds have beneficial
      effect on human health because they are strong antioxidants and they have potent
      cardiovascular, antidiabetic, antimicrobial and antitumoral activities. Due to
      all the properties described above, the demand for glucosinolates and their
      hydrolysis products has enormously increased, and therefore, new strategies that
      allow the production of these compounds to be improved are needed. The use of
      plant in vitro cultures is emerging as a biotechnological strategy to obtain
      glucosinolates and their derivatives. This work is focused on the biosynthesis of
      glucosinolates and the bioactivity of these compounds in plants. In addition, a
      detailed study on the strategies used to increase the production of several
      glucosinolates, in particular those synthesized in Brassicaceae, using in vitro
      plant cultures has been made. Special attention has been paid for increasing the
      production of glucosinolates and their derivatives using metabolic engineering.

PMID- 28492987
TI  - Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes
      in Water Regime.
AB  - Increasing efforts have been devoted to exploring the impact of environmental
      stresses on soil bacterial communities, but the work on the archaeal community is
      seldom. Here, we constructed microcosm experiments to investigate the responses
      of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two
      contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution.
      Ten DW cycles were exerted on the two soils with different copper levels,
      followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon
      index) in the high copper-level treatments increased over the incubation period,
      and archaeal community structure changed remarkably as revealed by the non-metric
      multidimensional scaling ordinations. In both soils, copper pollution altered the
      response of dominant operational taxonomic units (OTUs) to the DW disturbance.
      Throughout the incubation and recovery period, the resistance of archaeal
      abundance to the DW disturbance was higher in the copper-polluted soils than
      soils without pollution. Taken together, copper pollution altered the response of
      soil archaeal diversity and community composition to the DW disturbance and
      increased the resistance of the archaeal abundance. These findings have important
      implications for understanding soil microbial responses to ongoing environmental
      change.

PMID- 28492988
TI  - The Threat of Antimicrobial Resistance on the Human Microbiome.
AB  - Ubiquitous in nature, antimicrobial resistance (AMR) has existed long before the
      golden age of antimicrobials. While antimicrobial agents are beneficial to combat
      infection, their widespread use contributes to the increase in and emergence of
      novel resistant microbes in virtually all environmental niches. The human
      microbiome is an important reservoir of AMR with initial exposure occurring in
      early life. Once seeded with AMR, commensal organisms may be key contributors to
      the dissemination of resistance due to the interconnectedness of microbial
      communities. When acquired by pathogens however, AMR becomes a serious public
      health threat worldwide. Our ability to combat the threat of emerging resistance
      relies on accurate AMR detection methods and the development of therapeutics that
      function despite the presence of antimicrobial resistance.

PMID- 28492990
TI  - Field-Scale Pattern of Denitrifying Microorganisms and N2O Emission Rates
      Indicate a High Potential for Complete Denitrification in an Agriculturally Used
      Organic Soil.
AB  - More than 50% of all anthropogenic N2O emissions come from the soil. Drained
      Histosols that are used for agricultural purposes are particularly potent sources
      of denitrification due to higher stocks of organic matter and fertiliser
      application. However, conditions that favour denitrification can vary
      considerably across a field and change significantly throughout the year. Spatial
      and temporal denitrifier dynamics were assessed in a drained, intensely managed
      Histosol by focusing on the genetic nitrite and N2O reduction potential derived
      from the abundance of nirK, nirS and nosZ genes. These data were correlated with
      soil properties at two different points in time in 2013. N2O emissions were
      measured every 2 weeks over three vegetation periods (2012-2014). Very low N2O
      emission rates were measured throughout the entire period of investigation in
      accordance with the geostatistical data that revealed an abundance of microbes
      carrying the N2O reductase gene nosZ. This, along with neutral soil pH values, is
      indicative of high microbial denitrification potential. While the distribution of
      the microbial communities was strongly influenced by total organic carbon and
      nitrogen pools in March, the spatial distribution pattern was not related to the
      distribution of soil properties in October, when higher nutrient availability was
      observed. Different nitrite reducer groups prevailed in spring and autumn. While
      nirS, followed by nosZ and nirK, was most abundant in March, the latter was the
      dominant nitrite reductase in October.

PMID- 28492991
TI  - [Chronic kidney disease is not the same as chronic renal insufficiency].

PMID- 28492989
TI  - Temporal Variations of Microbiota Associated with the Immature Stages of Two
      Florida Culex Mosquito Vectors.
AB  - Microbiota associated with mosquito vector populations impact several traits of
      mosquitoes, including survival, reproduction, control, and immunity against
      pathogens. The influence of seasonal variations and mosquito species on mosquito
      gut microbiota is poorly understood. We sought to determine whether the mosquito
      microbiota associated with immature stages of two congeners (Culex coronator and
      Culex nigripalpus) differ temporally and between the two species. Using high
      throughput 16S rRNA gene sequence analysis, we characterized bacterial and
      archaeal communities found in the immature stages of the two Culex mosquito
      species sampled over three seasons to compare the diversity of bacteria between
      the two species. Beta diversity analyses of the larval microbiota sequences
      revealed that the two Culex species differed significantly, both temporally
      within each species and between the two species. Bacteria in Cx. coronator larvae
      were dominated by Alphaproteobacteria, mainly associated with Roseoccocus and
      unidentified species of Rhizobiales, and two unidentified species of
      Cyanobacteria. In contrast, Cx. nigripalpus was dominated by Thorsellia anophelis
      (Gammaproteobacteria), Clostridium, an unidentified species of Ruminococcacae
      (Clostridiales), and additional unidentified species associated with
      Erysipelotrichaceae (Erysipelotrichales), Bacteroidales, and Mollicutes. Results
      of our study revealed both seasonal and interspecies differences in bacterial
      community composition associated with the immature stages of Cx. coronator and
      Cx. nigripalpus vector populations in Florida. These results have important
      implications for our understanding of the underlying factors of variations in
      disease transmission among seasons, susceptibility to various pesticides, and
      other biotic factors, including the role of the microbiota on the spread of
      invasive species. In addition, our results suggest close associations of certain
      bacteria species with each of the two Culex species that will be further targeted
      for their potential in the development of microbial-based control strategies.

PMID- 28492992
TI  - [Choosing wisely recommendations in gastroenterology].
AB  - The Choosing wisely initiative of the German Society of Internal Medicine
      addresses procedures which are inadequately implemented (deficits in patient
      care) as well as those which are performed too often but without proven benefits
      for patients (misuse or overuse of health services). Based on their guidelines,
      The German Society of Gastroenterology, Digestive and Metabolic Diseases has
      identified such aspects and incorporated them into the respective
      recommendations.

PMID- 28492993
TI  - [Choosing wisely at the end of life : Recommendations of the German Society for
      Palliative Medicine (DGP)].
AB  - In addition to an overuse of unnecessary or no longer indicated diagnostic or
      therapeutic procedures at the end of life in the sense of overtreatment, there is
      often also a lack of therapeutic awareness in terms of a healthcare deficit, for
      example concerning the recognition and treatment of symptoms and complex burden
      of the disease. Sticking closely to the methodology of the German S3 "Palliative
      Medicine" guideline, the Choosing wisely recommendations of the German Society
      for Palliative Medicine address various examples of over- and underuse of
      healthcare services and treatment at the end of life, and thus also mirror basic
      principles of palliative medical care.

PMID- 28492994
TI  - Metabolic characteristics and renal dysfunction in 65 patients with tophi prior
      to gout.
AB  - Tophi typically occur many years after uncontrolled gout. Therefore, their
      development before gout remains unusual. Such patients might exhibit some
      characteristic differences compared with typical tophaceous gout patients. In
      this study, 65 tophaceous gout patients with tophi as the first sign of gout
      (tophi-first group) were enrolled. Their clinical characteristics were compared
      with those of 1421 patients whose tophi occurred after gout (tophi-after group).
      Compared with the tophi-after group, the tophi-first group had a significantly
      higher percentage of female patients and patients with elderly onset of disease
      and a lower percentage of patients with a positive family history; these patients
      had lower body mass indices, serum urate levels, and estimated glomerular
      filtration rates (eGFRs). Female sex and negative family history were identified
      as the principal determinants of tophi development before gout. The decreasing
      eGFR among the tophi-first group was not due to the group per se but was a result
      of older age, longer tophi duration, and hyperuricemia. The most common site of
      initial tophi occurrence in both groups was the toe. In the tophi-first group,
      the occurrence rates for initial tophi sites were significantly higher at the
      finger but were lower at the ankle. The tophi-first group exhibited distinct
      characteristics of age, gender, family history, BMI, serum urate levels, and
      initial tophi site. This group had fewer comorbidities but similar renal
      dysfunction compared with the tophi-after group. Thus, patients presenting with
      tophi should be treated promptly, even if they have no history of gout symptoms.

PMID- 28492995
TI  - General health status of long-term cervical cancer survivors after radiotherapy.
AB  - PURPOSE: To evaluate the global health status of long-term cervical cancer
      survivors (LCCS) who survived for more than 4 years after curative radiation
      treatment (RT). PATIENTS AND METHODS: Medical records of 562 women treated with
      RT in our institution between 2003 and 2010 were reviewed. Excluding 259 women
      who died of disease or were lost to follow-up, disease status and late
      morbidities were evaluated in 303 LCCS. Quality of life (QoL) was analyzed in 168
      LCCS using a questionnaire from the European Organization for the Research and
      Treatment of Cancer, and the results were compared with an age-matched healthy
      Korean female population. RESULTS: Median follow-up was 6.8 years (range 4.1-12.5
      years). There were 14 deaths (7 cancer specific) and 14 recurrences (5 local
      recurrences and 9 distant metastases). The median time to recurrence was 6.0
      years (range 4.1-8.2 years). Grade >=2 late toxicities were frequently observed
      in the bladder (19%) and small/large intestine (15%). Multivariate analysis
      revealed a higher rate of late toxicity in patients aged >=51 years at diagnosis
      (small/large intestine: hazard ratio, HR, 2.5 [1.2-5.5]; bladder: HR 2.4 [1.3
      4.5]; and bone: HR 4.3 [1.2-15.8]) than patients aged <51 years. Compared to the
      general population, LCCS exhibited a significantly higher rate of body image
      concerns, sexual dysfunction, lymphedema, and peripheral neuropathy. CONCLUSION:
      New recurrences occurred in 5% of LCCS and grade >=2 treatment-related
      morbidities were present in 33%. A significant proportion of LCCS also showed
      decreased cervical-cancer-specific QoL. These results suggest the need for long
      term surveillance and follow-up care for LCCS.

PMID- 28492996
TI  - Patient Perspectives on Barriers to Surgical Care and the Impact of Mobile
      Surgery in Ecuador.
AB  - BACKGROUND: An estimated 5 billion people worldwide lack access to timely safe
      surgical care (Gawande in Lancet 386(9993):523-525, 2015). A mere 6% of all
      surgical procedures occur in the poorest countries where over a third of the
      world's population lives (Meara et al. in Surgery 158(1):3-6, 2015). Mobile
      surgical units like the Cinterandes Foundation endeavor to bring surgical care
      directly to these communities who otherwise would lack access to safe surgery.
      This study examines the barriers patients encounter in seeking surgical care in
      rural communities of Ecuador and their impressions on how mobile surgery
      addresses such barriers. METHODS: Open interviews were conducted with
      Cinterandes' patients who had undergone an operation in the mobile surgical unit
      between 06/25/2013 and 06/25/2014 (n = 101). Interviews were structured to
      explore two main domains: (1) examining barriers patients have in accessing
      surgery, (2) assessing patients' opinion of how mobile surgery helped in
      overcoming such barriers. RESULTS: Patient inconvenience (70%), cost (21%), and
      lack of trust in local hospitals (24%) were the main cited barriers to surgical
      access. Increased patient convenience (53%), cheaper surgical care (34%), and
      trust in Cinterandes (47%) were the main cited benefits to mobile surgery.
      CONCLUSION: Mobile surgery provided by Cinterandes effectively overcomes many
      barriers patients encounter when seeking surgical care in rural Ecuador:
      decreased patient wait times, limited number of referrals to multiple locations,
      and decreased cost. Partnering with local clinics within the communities and
      bringing care much closer to patients' homes may provide a better patient
      friendly health care delivery system for rural Ecuador.

PMID- 28492997
TI  - Routine Contrast Esophagram in Anastomotic Leaks After Esophagectomy;
      Methodological Issues on Diagnostic Value: Reply.

PMID- 28492998
TI  - Enhanced Recovery After Surgery: Can We Rely on the Key Factors or Do We Need the
      Bel Ensemble?
AB  - BACKGROUND: The success of enhanced recovery (ERAS) pathways depends on the
      actual application of the intended protocol (adherence), but its full
      implementation remains challenging. In order to potentially streamline the
      pathway, it is indispensable to know the impact of individual items and the
      entire protocol on clinical outcomes. METHODS: Retrospective analysis including
      all consecutive colorectal ERAS patients since implementation (May 2011) until
      February 2014; demographics, adherence and outcomes were retrieved from a
      prospectively maintained database. Primary outcome was the impact of individual
      item and of the entire protocol on complications (overall and major) and length
      of hospital stay. Statistical analysis included logistic multivariate regression
      and adjustment for confounding factors. RESULTS: There were 328 patients with
      complete data sets analyzed. A minimally invasive approach [odd ratio (OR) 0.62;
      confidence interval (CI) 0.4-0.9] was significantly associated with less overall
      complications. In contrast, the use of prophylactic nasogastric tubes (OR 3.18;
      CI 1.4-7.4), prophylactic abdominal and pelvic drains (OR 1.96; 1.2-3.2) and
      intraoperative thoracic epidural analgesia (OR 1.76; CI 1.3-2.4) were associated
      with more overall complications. Minimal invasive approach was further associated
      with reduced hospital stay (OR 0.5; CI 0.4-0.7) and less major complications (OR
      0.58; CI 0.4-0.8). Higher adherence to the entire ERAS protocol was associated
      with significantly less complications (P < 0.001) and shorter hospital stay (P <
      0.001). CONCLUSIONS: Minimally invasive surgery was the single most important
      component of the ERAS pathway while nasogastric tubes, drains and epidurals
      should be avoided. Overall, increasing adherence with the protocol was associated
      with better outcomes and should be the goal.

PMID- 28492999
TI  - Physical activity improves cognition: possible explanations.
AB  - Good cognitive abilities (CA) enable autonomy, improve social inclusion and act
      preventively. Regular physical activity (PA) reduces the risk of developing
      Alzheimer's disease (AD) and, at the same time, it reduces the decline of CA and
      stimulates neurogenesis. So PA in connection with cognitive training, nutrition
      and social interaction has a positive effect on general CA and the central
      nervous system, the central executor, memory and attention, and reduces the
      likelihood of developing dementia. Our objective was to examine which sort and
      intensity of PA is preferred. We did a review, restricted only to human studies,
      of transparent scientific articles and sample surveys carried out and published
      in the period between 2001 and 2016 based on the keywords: age, aging, physical
      activity, physical abilities, cognitive abilities, memory and Alzheimer's
      disease. According to results CA and PA interact, as an increasing PA of only 10%
      reduces the risk of dementia and AD significantly. However, there is a question
      of appropriate intensity of exercise. Low-intensity aerobic exercise has a
      positive effect on the visual spatial perception and attention, whereas moderate
      PA has a positive impact on general CA, working memory and attention, verbal
      memory and attention and vice versa. While the majority of experts recommends
      vigorous or moderate exercise, many of them warn that higher intensity requires
      more attention to PA and less to cognitive processes, particularly in terms of
      reducing reactions, selective attention and flexibility to tasks. There is also a
      further question what PA should be like. Although some experts believe that the
      best combination is aerobic PA and exercises against resistance, it is not
      entirely clear whether the improvement in CA is a result of cardiac vascular
      fitness. On the other hand, for most elderly it is more suitable to perform an
      alternative form (not anaerobic) of PA due to comorbidity and actual fragility.
      We can conclude that PA has a positive effect on CA, but an appropriate intensity
      and the type of exercise remain unsolved. For the relevant findings it is
      absolutely necessary to have an interdisciplinary approach.

PMID- 28493000
TI  - Serological and molecular tests for the diagnosis of Strongyloides stercoralis
      infection in dogs.
AB  - Strongyloides stercoralis can cause severe infection both in humans and dogs.
      Coproparasitological examination has low sensitivity for the diagnosis of this
      parasite; hence, different diagnostic techniques have been implemented. However,
      serology and molecular methods have been assessed almost exclusively in humans.
      In this study, two serologic assays and a real-time PCR (RT-PCR), routinely used
      for the diagnosis of strongyloidiasis in humans, have been tested for the
      diagnosis in dogs. Five dogs living in the same kennel in Bari, southern Italy,
      were diagnosed with S. stercoralis infection by detection of larvae in fecal
      samples processed by the Baermann method. Serum, fecal, and tissue (lungs,
      scraping of intestinal tract) samples from the same dogs were tested with two
      serologic assays (commercial ELISA, in-house IFAT) and with an in-house RT-PCR,
      routinely used for diagnosis in humans. IFAT was positive in all serum samples,
      ELISA in 3/7 (42.8%) samples. RT-PCR was positive in all pre-treatment fecal
      samples, in all fecal debris, and in intestinal scraping (three samples from the
      same deceased dog). The results suggest that IFAT and RT-PCR techniques routinely
      used for S. stercoralis diagnosis in humans could be useful for the diagnosis of
      the infection in dogs.

PMID- 28493001
TI  - Study on the tolerance and adaptation of rats to Angiostrongylus cantonensis
      infection.
AB  - Angiostrongylus cantonensis (A. cantonensis) is the most common infectious agent
      causing eosinophilic meningitis. As an important food-borne parasitic disease,
      angiostrongyliasis cantonensis is an emerging infectious disease which brings
      severe harm to central nerve system of human. Rat, one of the few permissive
      hosts of A. cantonensis known to date, plays an indispensable role in the worm's
      life cycle. However, the tolerance and adaptation of rat to A. cantonensis
      infection is rarely understood. In this study, we infected rats with different
      numbers the third stage larvae (L3) of A. cantonensis and explored their
      tolerance through analysis on survival curve, neurological function score, and
      detection of pathological damages in organs including the brain, lung, and heart
      of the animals. Results indicated that rats' survival condition worsens, and body
      weight dropped more significantly as more worms were used for infection. Death
      appeared in groups infected with 80 and more A. cantonesnsis per rat. Morris
      water maze revealed that the neurological function of rats damaged gradually with
      increasing infection number of A. cantonensis larvae. When the number of infected
      parasite exceeded 240 per animal, rats showed significant neurological
      impairments. Collection of A. cantonensis from rat lung after 35 days of
      infection implied an upper limit for worm entry, and the average length of worm
      was inversely proportional to the infection amount, while the ratio between
      female and male worms was positively related to the infection number. The degree
      of pulmonary and cardiac inflammation was proportional to the infection number of
      A. cantonensis. Meanwhile, there existed considerable amount of adult worms in
      rat's right atrium and right ventricle, leading to a right heart myocardial
      inflammation. The present study firstly reports the tolerance and adaptation of
      rat, a permissive host of A. cantonensis to its infection, which will not only
      provide accurate technical parameters for maintaining A. cantonensis life cycle
      under laboratory conditions but also help unveil the underlying mechanism of the
      distinct pathological outcomes in the permissive and non-permissive hosts with A.
      cantonensis infection.

PMID- 28493002
TI  - Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded
      Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions.
AB  - Incorporation of antioxidants into sunscreens is a logical approach, yet co
      delivery of them with UV filters is a challenge. Here, we purposed a combination
      therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated
      on upper skin while the antioxidant, melatonin, can penetrate deeper layers to
      show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate
      Pickering emulsion were prepared separately. Lyophilized elastic niosomes were
      dispersed into the Pickering emulsion to prepare the proposed combination
      formulation. The characterization studies of the formulations revealed that
      elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering
      emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin
      loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a
      PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter
      size of the combination formulation was 27.8 MUm. Ex vivo permeation studies
      revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated
      through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin
      accumulated in the skin after 24 h. Cell culture studies with real-time cell
      analyzer showed that the proposed formulation consist of melatonin-loaded elastic
      niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on
      the cell proliferation and viability. According to alpha,alpha-diphenyl-beta
      picrylhydrazyl free radical scavenging method, the proposed formulation showed as
      high antioxidant activity as melatonin itself. It is concluded that the proposed
      formulation would be a promising dual therapy for UV-induced skin damage with co
      delivery strategy.

PMID- 28493003
TI  - Bio-shielding In Situ Forming Gels (BSIFG) Loaded With Lipospheres for Depot
      Injection of Quetiapine Fumarate: In Vitro and In Vivo Evaluation.
AB  - Quetiapine fumarate (QF), an anti-schizophrenic drug, suffers from rapid
      elimination and poor bioavailability due to extensive first-pass effect.
      Intramuscularly (IM) injected lipospheres were designed to enhance the drug's
      bioavailability and extend its release. A central composite design was applied to
      optimize the liposphere preparation by a melt dispersion technique using
      Compritol(r) 888 ATO or glyceryl tristearate as lipid component and polyvinyl
      alcohol as surfactant. Lipospheres were evaluated for their particle size,
      entrapment efficiency, and in vitro release. The optimized QF lipospheres were
      prepared using a Compritol(r) 888 ATO fraction of 18.88% in the drug/lipid
      mixture under a stirring rate of 3979 rpm. The optimized lipospheres were loaded
      into a thermoresponsive in situ forming gel (TRIFG) and a liquid crystalline in
      situ forming gel (LCIFG) to prevent in vivo degradation by lipases. The loaded
      gels were re-evaluated for their in vitro release and injectability.
      Bioavailability of QF from liposphere suspension and bio-shielding in situ gels
      loaded with QF lipospheres were assessed in rabbits compared to drug suspension.
      Results revealed that the AUC0-72 obtained from the liposphere-loaded TRIFG was
      ~3-fold higher than that obtained from the aqueous drug suspension indicating the
      bio-shielding effect of Poloxamer(r) 407 gel to inhibit the biodegradation of the
      lipospheres prolonging the residence of the drug in the muscle for higher
      absorption. Our results propose that bio-shielding in situ Poloxamer(r) 407 gels
      loaded with lipospheres is promising for the development of IM depot injection of
      drugs having extensive first-pass metabolism and rapid elimination.

PMID- 28493004
TI  - Efavirenz Dissolution Enhancement IV-Antisolvent Nanocrystallization by
      Sonication, Physical Stability, and Dissolution.
AB  - Efavirenz is a fundamental drug in the HIV therapy; however, it has a low
      bioavailability due to low water solubility. Particle nanonization should enhance
      its dissolution and therefore its bioavailability. Nanocrystallization is a
      promising technique for preparing drug nanocrystals. A solution containing
      efavirenz (EFV) and methanol was added to an aqueous solution of particle
      stabilizers, under sonication. The adequate polymer stabilizer and its
      concentration and drug load were evaluated. Particle size and zeta potential of
      suspensions were measured. Nanosuspensions were freeze-dried and the resulting
      powder was characterized by some techniques, with special attention to
      dissolution. Particle size and zeta potential analysis showed that HMPC and PVP
      were the most suitable polymers. All samples prepared with these stabilizers had
      nanosized particles and proper zeta potential; however, sedimentation and
      particle growth were detected with TurbiscanTM. Time-related destabilization
      occurred when the lowest polymer concentration of 20% was used. SEM analysis of
      the dried powder shows film formation for suspensions with 40% of polymer and
      particle aggregation in samples with less polymer. Dissolution profiles of
      samples were higher than EFV raw material, although the lower the polymer
      concentration, the higher the dissolution.

PMID- 28493005
TI  - Erratum to: Effects of aging on the relationship between cognitive demand and
      step variability during dual-task walking.

PMID- 28493006
TI  - Activity of Combined Antifungal Agents Against Multidrug-Resistant Candida
      glabrata Strains.
AB  - In this study, we evaluated the in vitro activity of echinocandins, azoles, and
      amphotericin B alone and in combination against echinocandin/azole-sensitive and
      echinocandin/azole-resistant Candida glabrata isolates. Susceptibility tests were
      performed using the broth microdilution method in accordance with the Clinical
      and Laboratory Standards Institute document M27-A3. The checkerboard method was
      used to evaluate the fractional inhibitory concentration index of the
      interactions. Cross-resistance was observed among echinocandins; 15% of the
      isolates resistant to caspofungin were also resistant to anidulafungin and
      micafungin. Synergistic activity was observed in 70% of resistant C. glabrata
      when anidulafungin was combined with voriconazole or posaconazole. Higher (85%)
      synergism was found in the combination of caspofungin and voriconazole. The
      combinations of caspofungin with fluconazole, posaconazole and amphotericin B,
      micafungin with fluconazole, posaconazole and voriconazole, and anidulafungin
      with amphotericin B showed indifferent activities for the majority of the
      isolates. Anidulafungin combined with fluconazole showed the same percentage of
      synergism and indifference (45%). Antagonism was detected in 50% of isolates when
      micafungin was combined with amphotericin B. Combinations of echinocandins and
      antifungal azoles have great potential for in vivo assays which are required to
      evaluate the efficacy of these combinations against multidrug-resistant C.
      glabrata strains.

PMID- 28493007
TI  - Gastrointestinal endoscopy in patients receiving novel direct oral
      anticoagulants: results from the prospective Dresden NOAC registry.
AB  - BACKGROUND: Patients receiving direct-acting, non-vitamin K oral anticoagulants
      (NOAC) frequently undergo gastrointestinal endoscopies (GIE) but little is known
      on the management and outcome of these interventions. METHODS: With use of data
      from an ongoing, prospective, noninterventional registry of NOAC patients, the
      management and outcome of GIE were evaluated with use of standard event
      definitions. Patients undergoing GIE were categorized into two subgroups: (1)
      scheduled GIE (scheduled appointment, no acute bleeding) and (2) unscheduled GIE
      (unscheduled including management of acute gastrointestinal bleeding). The rates
      of major bleeding complications, cardiovascular complications, and all-cause
      death within 30 days after the procedure were evaluated. RESULTS: Between October
      1, 2011, and March 31, 2015, 492 patients underwent a total of 713 GIE (44.5%
      gastroscopies, 53.0% colonoscopies, 2.5% endoscopic retrograde
      cholangiopancreatography procedures), with 70.0% being scheduled procedures and
      30.0% being unscheduled procedures. Endoscopies were performed within 24 h after
      the last NOAC intake in 45 of 713 cases (6.3%), between 24 and 48 h after the
      last intake in 336 cases (47.1%), and after NOAC therapy interruption for more
      than 48 h in 213 cases (29.9%). Heparin bridging therapy was used in 180 of 713
      procedures (25.3%) and predominantly (170/180; 94.4%) in cases of NOAC therapy
      interruption for longer than 72 h. Until day 30 after the procedure, the event
      rates were 1.4% for cardiovascular events and 0.7% for major bleeding events.
      CONCLUSION: Continuation or short-term interruption of NOAC therapy seems to be a
      safe strategy for GIE. Heparin bridging therapy is predominantly used in cases of
      prolonged NOAC therapy interruption.

PMID- 28493008
TI  - Role of family history and tumor location on prognosis of patients with
      colorectal cancer and synchronous metastases.
AB  - BACKGROUND/AIMS: Family history of colorectal cancer and tumor location along
      colon-rectum have been reported as prognostic factors. The aim of the current
      study is to analyze the role of both on overall survival in a series of patients
      with metastatic colorectal cancer with synchronous metastases. METHODS: A
      retrospective mono-institutional analysis has been performed on patients, who
      received chemotherapy from 2004 to 2008. A Cox proportional-hazards regression
      was used to calculate hazard ratio (HR) for death, after adjustment for other
      variables (tumor metastasectomy, number of organs involved with metastases,
      number of anti-neoplastic drugs, age, sex, tumor grade, baseline CEA). RESULTS:
      Two hundred and seven patients were included in the study. Only tumor
      metastasectomy was related with a better overall survival (HR 4.995; P < 0.001),
      whereas a positive family history was associated with a poor prognosis (HR 0.386;
      P = 0.021). After exclusion of rectal tumors, the negative prognostic effect of a
      positive family history appeared limited to patients with a left-sided colon
      cancer (HR 0.183; P = 0.036). CONCLUSION: Family history for colorectal cancer in
      a first-degree relative, and not tumor location, has a significant relationship
      with the prognosis of patients with a colorectal cancer and synchronous
      metastases.

PMID- 28493009
TI  - Perivesical cystic duct of the gallbladder.

PMID- 28493010
TI  - Multiple long bone cysts revealed by MRI in trichorhinophalangeal syndrome type
      II predisposing to pathological fractures.
AB  - Trichorhinophalangeal syndrome type II is a rare genetic disorder with the few
      published case reports mainly reporting the radiographic skeletal manifestations.
      There are no published imaging reports of long bone cysts involving multiple
      bones in this condition. We report a unique case of bone cysts involving multiple
      long bones detected with MRI in a patient with trichorhinophalangeal syndrome
      type II complicated by a subsequent pathological fracture. It is possible that
      the bone cysts are a previously undescribed feature of this syndrome; however,
      the evidence is insufficient to establish a definite association. Chromosomal
      abnormality identified in this patient is consistent with trichorhinophalangeal
      syndrome type II with no unusual features. Although the nature of these bone
      cysts is unclear, they are one of the causes of the known increased fracture risk
      observed in this syndrome.

PMID- 28493011
TI  - MRI of thoracic outlet syndrome in children.
AB  - Thoracic outlet syndrome is caused by compression of the neurovascular bundle as
      it passes from the upper thorax to the axilla. The neurovascular bundle can be
      compressed by bony structures such as the first rib, cervical ribs or bone
      tubercles, or from soft-tissue abnormalities like a fibrous band, muscle
      hypertrophy or space-occupying lesion. Thoracic outlet syndrome commonly affects
      young adults but can be seen in the pediatric age group, especially in older
      children. Diagnosis is based on a holistic approach encompassing clinical
      features, physical examination findings including those triggered by various
      maneuvers, electromyography, nerve conduction studies and imaging. Imaging is
      performed to confirm the diagnosis, exclude mimics and classify thoracic outlet
      syndrome into neurogenic, arterial, venous or mixed causes. MRI and MR
      angiography are useful in this process. A complete MRI examination for suspected
      thoracic outlet syndrome should include the assessment of anatomy and any
      abnormalities using routine sequences, vessel assessment with the arms in
      adduction by MR angiography and assessment of dynamic compression of vessels with
      abduction of the arms. The purpose of this paper is to describe the anatomy of
      the thoracic outlet, causes of thoracic outlet syndrome, the MR imaging
      techniques used in its diagnosis and the principles of image interpretation.

PMID- 28493012
TI  - EEG Microstate Correlates of Fluid Intelligence and Response to Cognitive
      Training.
AB  - The neurobiological correlates of human fluid intelligence (Gf) remain elusive.
      Here, we demonstrate that spatiotemporal dynamics of EEG activity correlate with
      baseline measures of Gf and with its modulation by cognitive training. EEG
      dynamics were assessed in 74 healthy participants by examination of fast
      changing, recurring, topographically-defined electric patterns termed
      "microstates", which characterize the electrophysiological activity of
      distributed cortical networks. We find that the frequency of appearance of
      specific brain topographies, spatially associated with visual (microstate B) and
      executive control (microstate C) networks, respectively, is inversely related to
      Gf scores. Moreover, changes in Gf scores with cognitive training are inversely
      correlated with changes in microstate properties, indicating that the changes in
      brain network dynamics are behaviorally relevant. Finally, we find that cognitive
      training that increases Gf scores results in a posterior shift in the topography
      of microstate C. These results highlight the role of fast-changing brain
      electrical states in individual variability in Gf and in the response to
      cognitive training.

PMID- 28493013
TI  - The effects of Hurricane Sandy on trauma center admissions.
AB  - BACKGROUND: Hurricane Sandy was a particularly unusual storm with regard to both
      size and location of landfall. The storm landed in New Jersey, which is unusual
      for a tropical storm of such scale, and created hazardous conditions which caused
      injury to residents during the storm and in the months following. This study aims
      to describe differences in trauma center admissions and patterns of injury during
      this time period when compared to a period with no such storm. METHODS: Data were
      collected for this study from patients who were admitted to the trauma center at
      Morristown Medical Center during Hurricane Sandy or the ensuing cleanup efforts
      (patients admitted between 29 October 2012 and 27 December 2012) as well as a
      control group consisting of all patients admitted to the trauma center between 29
      October 2013 and 27 December 2013. Patient information was collected to compare
      the admissions of the trauma center during the period of the storm and cleanup to
      the control period. RESULTS: A total of 419 cases were identified in the storm
      and cleanup period. 427 were identified for the control. Striking injuries were
      more common in the storm and cleanup group by 266.7% (p = 0.0107); cuts were more
      common by 650.8% (p = 0.0044). Medical records indicate that many of these
      injuries were caused by Hurricane Sandy. Self-inflicted injuries were more common
      by 301.3% (p = 0.0294). There were no significant differences in the total number
      of patients, mortality, or injury severity score between the two cohorts.
      CONCLUSION: The data we have collected show that the conditions caused by
      Hurricane Sandy and the following cleanup had a significant effect on injury
      patterns, with more patients having been injured by being struck by falling or
      thrown objects, cut while using tools, or causing self-inflicted injuries. These
      changes, particularly during the cleanup period, are indicative of environmental
      changes following the storm which increase these risks of injury.

PMID- 28493014
TI  - Commentary on a case of body pushing and radiation exposure in screening of body
      packing.

PMID- 28493015
TI  - U.S. News Media Coverage of Pharmaceutical Pollution in the Aquatic Environment:
      A Content Analysis of the Problems and Solutions Presented by Actors.
AB  - Pharmaceutical pollution in the aquatic environment is an issue of concern that
      has attracted attention by the news media. Understanding the factors that
      contribute to media framing of pharmaceutical pollution may lead to a better
      understanding of the management and governance of this issue, including why these
      pollutants are generally unregulated at this time. This study conducted a content
      analysis of 405 newspaper articles (81 had substantive information on the topic)
      from 2007 to 2014, using the search terms "water" and "pharmaceuticals" in the
      Chicago Tribune, Denver Post, Los Angeles Times, New York Daily News, New York
      Times, USA Today, Wall Street Journal, and Washington Post. We sought to analyze
      the factors that contributed to the news media presentation of pharmaceutical
      pollution in the United States, including the presentation of the risks/safety
      and solutions by various actors. We found that the primary issues in the news
      media were uncertainty regarding public health and harm to the environment. The
      primary solutions recommended within the news media were implementing additional
      water treatment technologies, taking unused pharmaceuticals to predetermined
      sites for disposal (take-back programs), and trash disposal of unused
      pharmaceuticals. Water utilities and scientists presented improved water
      treatment technology, government actors presented take-back programs, and
      pharmaceutical representatives, while sparsely involved in the news media,
      presented trash disposal as their primary solutions. To advance the understanding
      of the management of pharmaceutical pollution, this article offers further
      insight into the debate and potential solutions within the news media
      presentation of this complex scientific topic.

PMID- 28493016
TI  - Modelling the Risk Posed by the Zebra Mussel Dreissena polymorpha: Italy as a
      Case Study.
AB  - We generated a risk map to forecast the potential effects of the spreading of
      zebra mussels Dreissena polymorpha across the Italian territory. We assessed the
      invader's potential impact on rivers, lakes, watersheds and dams at a fine
      grained scale and detected those more at risk that should be targeted with
      appropriate monitoring. We developed a MaxEnt model and employed weighted overlay
      analyses to detect the species' potential distribution and generate risk maps for
      Italy. D. polymorpha has a greater probability of occurring at low to medium
      altitudes in areas characterised by fluviatile deposits of major streams.
      Northern and central Italy appear more at risk. Some hydroelectric power dams are
      at high risk, while most dams for irrigation, drinkable water reservoirs and
      other dam types are at medium to low risk. The lakes and rivers reaches
      (representing likely expansion pathways) at medium-high or high risk mostly occur
      in northern and central Italy. We highlight the importance of modelling potential
      invasions on a country scale to achieve the sufficient resolution needed to
      develop appropriate monitoring plans and prevent the invader's harmful effects.
      Further high-resolution risk maps are needed for other regions partly or not yet
      colonised by the zebra mussel.

PMID- 28493017
TI  - Ecological Equivalence Assessment Methods: What Trade-Offs between
      Operationality, Scientific Basis and Comprehensiveness?
AB  - In many countries, biodiversity compensation is required to counterbalance
      negative impacts of development projects on biodiversity by carrying out
      ecological measures, called offset when the goal is to reach "no net loss" of
      biodiversity. One main issue is to ensure that offset gains are equivalent to
      impact-related losses. Ecological equivalence is assessed with ecological
      equivalence assessment methods taking into account a range of key considerations
      that we summarized as ecological, spatial, temporal, and uncertainty. When
      equivalence assessment methods take into account all considerations, we call them
      "comprehensive". Equivalence assessment methods should also aim to be science
      based and operational, which is challenging. Many equivalence assessment methods
      have been developed worldwide but none is fully satisfying. In the present study,
      we examine 13 equivalence assessment methods in order to identify (i) their
      general structure and (ii) the synergies and trade-offs between equivalence
      assessment methods characteristics related to operationality, scientific-basis
      and comprehensiveness (called "challenges" in his paper). We evaluate each
      equivalence assessment methods on the basis of 12 criteria describing the level
      of achievement of each challenge. We observe that all equivalence assessment
      methods share a general structure, with possible improvements in the choice of
      target biodiversity, the indicators used, the integration of landscape context
      and the multipliers reflecting time lags and uncertainties. We show that no
      equivalence assessment methods combines all challenges perfectly. There are trade
      offs between and within the challenges: operationality tends to be favored while
      scientific basis are integrated heterogeneously in equivalence assessment methods
      development. One way of improving the challenges combination would be the use of
      offset dedicated data-bases providing scientific feedbacks on previous offset
      measures.

PMID- 28493018
TI  - Emerging role of miRNA in attention deficit hyperactivity disorder: a systematic
      review.
AB  - Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder
      whose aetiology still remains elusive. Nevertheless, evidence supports a high
      genetic contribution that interacts with environmental factors, also known to
      modulate epigenetic processes. These epigenetic modulators are a class of non
      coding RNAs, microRNAs (miRNAs), known as post-transcriptional regulators, which
      have emerged as prospective players in neuropsychiatric disorders since they play
      a role in brain development, synapse formation, and the fine-tuning of genes
      underlying synaptic and memory formation. Here, we review the current literature
      following a systematic search up until August 2016. The keywords used were
      "ADHD", "attention deficit hyperactivity disorder", "attention hyperactivity" in
      combination with "miRNA" or "microRNA". A total of 9 studies out of 34 met
      inclusion criteria. The results provide preliminary information, shedding light
      on two important aspects. First, it depicts that miRNAs modulate expression of
      genes (BDNF, DAT1, HTR2C, HTR1B, SNAP-25) linked to ADHD aetiology. Dysregulation
      of miRNAs affects regulatory mechanisms of aforementioned genes, which may affect
      neurodevelopmental processes leading to alterations. Secondly, altered peripheral
      miRNA levels are observed in both ADHD animal model and humans, suggesting a
      notion of utilizing circulatory miRNA in disease diagnosis. Therefore,
      deciphering the role of miRNAs in ADHD seems a promising step in understanding
      its aetiology.

PMID- 28493019
TI  - Surgical treatment of advanced penile cancer.
AB  - PURPOSE: To evaluate the therapeutic effect of surgery in patients with advanced
      penile cancer, who have a dismal prognosis. PATIENTS AND METHODS: Between
      September 2007 and July 2015, we treated 12 patients with surgical therapy.
      RESULTS: The median follow-up period for all the patients was 16 months (range 4
      60 months). The outcome and concomitant symptoms were analyzed, and the survival
      rates were calculated. Three of the patients are currently alive. The median
      overall survival of the patients was 9 months (range 4-13 months). CONCLUSION:
      The present results suggest that surgery is a valuable treatment option for
      patients with advanced penile cancer. The prognosis of advanced penile cancer is
      closely related to lymph node and distant metastases. Flap repair can solve the
      problem of large area skin defect. Advanced penile cancer is difficult to treat
      regardless of chemotherapy or radiotherapy, and surgery cannot prolong the lives
      of patients. However, the dissection of lesions and repair of large area skin
      defects can dramatically improve the quality of life of patients, especially
      those with locally advanced disease without distant metastasis.

PMID- 28493020
TI  - Development and validation of an analytical method based on liquid chromatography
      tandem mass spectrometry detection for the simultaneous determination of 13
      relevant wastewater-derived contaminants in lettuce.
AB  - We present an analytical method developed and validated to study the potential
      uptake of 13 selected drugs (ten pharmaceuticals, one illicit drug, and two
      transformation products) into lettuce plants from contaminated water and soil.
      Some of the selected drugs (i.e., cocaine, methadone, cis-diltiazem, valsartan,
      and valsartan acid), which are commonly present in treated wastewater, were
      investigated for the first time in plant tissues. The method is based on
      ultrasonic solvent extraction with acetonitrile-methanol (1:1, v/v) and
      subsequent automated extract cleanup and analysis by means of online solid-phase
      extraction-liquid chromatography-tandem mass spectrometry. Optimum extraction
      conditions were selected after evaluation of analyte recoveries with four
      different extraction techniques (ultrasonic solvent extraction, solid-liquid
      extraction, pressurized liquid extraction, and a "quick, easy, cheap, effective,
      rugged, and safe" based method) and six different solvent mixtures. Furthermore,
      two different solid-phase extraction cleanup sorbents were evaluated. The method
      developed has high sensitivity (with limits of detection between 0.1 and 12.6 ng
      per gram dry weight and limits of quantification between 0.5 and 42.0 ng per gram
      dry weight), satisfactory accuracy (with analyte relative recoveries above 80%
      for all analytes but acridone and oxcarbazepine), and good repeatability (with
      relative standard deviations below 9% for all analytes). As part of the
      validation procedure, the analytical method was applied to the analysis of
      lettuce plants irrigated with water fortified with the selected compounds for the
      entire growing period. The results obtained evidenced the transfer of all the
      investigated drugs into lettuce leaves. Graphical Abstract ?.

PMID- 28493021
TI  - Cobalt oxyhydroxide nanoflakes with intrinsic peroxidase catalytic activity and
      their application to serum glucose detection.
AB  - Cobalt oxyhydroxide (CoOOH) nanoflakes, an emerging type of two-dimensional
      nanomaterial, show great potential for use in molecular detection. Previous
      assays utilizing such materials have largely been based on their outstanding
      fluorescence quenching ability and oxidizing power. Herein, we report the
      intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes, and
      we show how this activity can be employed for glucose detection. We found that,
      in the presence of hydrogen peroxide (H2O2), the nanoflakes accelerated the
      conversion of peroxidase substrates such as 3,3',5,5'-tetramethylbenzidine (TMB)
      into colored products. By combining the CoOOH nanoflakes with the biological
      enzyme glucose oxidase (GOx), we developed a colorimetric method for the
      detection of glucose within the concentration range 5.3-500 MUM. The proposed
      method was applied to detect elevated blood glucose levels in diabetic patients,
      and the intense color change induced by elevated glucose levels was found to be
      readily apparent to the naked eye, proving the utility of our assay for point-of
      care testing. Graphical abstract The intrinsic peroxidase-like activity of cobalt
      oxyhydroxide (CoOOH) nanoflakes was exploited to enable the direct visualization
      of elevated glucose levels in sera from diabetic patients.

PMID- 28493022
TI  - In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone
      (Haliotis rubra) viscera hydrolysate.
AB  - Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti
      coagulant activities. In this study, a hydrolysate was prepared from blacklip
      abalone (Haliotis rubra) viscera using papain and bromelain and fractionated
      using ion exchange and size exclusion chromatography. Hydrolysates and fractions
      were investigated for in vitro thrombin inhibition mediated through heparin
      cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood.
      On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited
      thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5
      MUg/mL compared with 2.1 MUg/mL for standard heparin. Fractionation concentrated
      HCII-mediated thrombin inhibition down to an IC50 of 1.8 MUg/mL and improved anti
      coagulant activities by significantly delaying clotting time. This study
      confirmed the presence of anti-thrombotic and anti-coagulant molecules in
      blacklip abalone viscera and demonstrated that these activities can be enriched
      with a simple chromatography regime. Blacklip abalone viscera warrant further
      investigation as a source of nutraceutical or functional food ingredients.
      Graphical abstract Schematic showing preparation of bioactive extracts and
      fractions from blacklip abalone.

PMID- 28493023
TI  - The paramedian supracerebellar infratentorial approach.
AB  - BACKGROUND: Lesions of the superior cerebellar surface, pineal region, lateral
      and dorsal midbrain and mesial temporal lobe are challenging to treat and often
      require neurosurgical intervention. METHODS: The paramedian variation of the
      supracerebellar infratentorial approach utilizes the downward slope of the
      cerebellum to facilitate exposure and the lower density of cerebellar bridging
      veins away from the midline decreases the need to sacrifice larger venous
      channels. We also discuss our experiences with the approach, and some of the
      drawbacks and nuances that we have encountered as it has evolved over the years.
      CONCLUSIONS: This approach is versatile and effective and the authors' surgical
      approach of choice for resecting these challenging lesions.

PMID- 28493024
TI  - De novo vertebral artery dissecting aneurysm after internal trapping of the
      contralateral vertebral artery.
AB  - We present the case of a de novo vertebral artery dissecting aneurysm (VADA)
      after endovascular trapping of a ruptured VADA on the contralateral side. The
      first ruptured VADA involved the posterior inferior cerebellar artery, which was
      successfully treated by endovascular internal trapping using a stent. A follow-up
      study at 3 months revealed a de novo VADA on the contralateral side. The second
      VADA was successfully embolized using coils while normal arterial flow in the
      vertebral artery was preserved using a stent. Increased hemodynamic stress may
      cause the development of a de novo VADA on the contralateral side.

PMID- 28493025
TI  - CRNDE Expression Positively Correlates with EGFR Activation and Modulates Glioma
      Cell Growth.
AB  - BACKGROUND: The long non-coding RNA CRNDE has emerged as an important regulator
      in carcinogenesis and cancer progression. While CRNDE has previously been found
      to be the most highly upregulated lncRNA in glioma, detailed information on its
      roles in regulating cancer cell growth remains limited. OBJECTIVE: In the present
      study, we aimed at exploring the functional roles and underlying mechanisms of
      CRNDE in glioma. METHODS: We applied microarray data analysis to determine the
      prognostic significance of CRNDE in glioma patients and its correlation with
      epidermal growth factor receptor (EGFR) activation. EGFR inhibition was used to
      confirm the role of EGFR in regulating CRNDE expression. Functional studies were
      performed upon CRNDE silencing to explore its role in gliomagenesis. RESULTS: We
      confirm that CRNDE acts as an oncogene that is highly up-regulated in glioma, and
      high CRNDE expression correlates with poor prognosis in glioma patients. We
      further demonstrate that the expression of CRNDE correlates with EGFR activation.
      EGF and EGFR tyrosine kinase inhibitor (TKI) enhance and block the up-regulation
      of CRNDE expression, respectively, suggesting that EGFR signaling may positively
      regulate CRNDE expression. Functional assays show that CRNDE depletion inhibits
      glioma cell growth both in vitro and in vivo, and is associated with induced
      cellular apoptosis with decreased Bcl2/Bax ratio. CONCLUSIONS: Our findings
      suggest that the aberrant expression of CRNDE may be mediated by activated EGFR
      signaling and play significant roles in gliomagenesis.

PMID- 28493026
TI  - Structural and functional characterization of a novel immunomodulatory
      glycoprotein isolated from ajowan (Trachyspermum ammi L.).
AB  - Ajowan (Trachyspermum ammi L.) spice has been used in food preparations and also
      as a traditional medicine in Ayurveda. Although a number of pharmacological
      activities have been attributed to ajowan, its role in immunomodulation is not
      known. The main objective of the present study is to examine the macromolecular
      immunomodulatory components. Macrophage activation was studied by nitric oxide
      (NO) release, phagocytosis and secretion of pro-inflammatory cytokines as the
      markers. Ethanol precipitate (fractional) of ajowan aqueous extract was subjected
      to conventional chromatography (Q Sepharose followed by Bio-Gel P-100). One of
      the proteins (30.7 kDa; ajowan glycoprotein or Agp) showed effective mitogenic
      activity towards splenocytes. Agp is a O-linked glycoprotein with the glycans
      contributing to one-third of the molecular mass. It has a high content of
      glutamic acid, serine, aspartic acid and proline whereas galactose (45.7%),
      arabinose (34.5%), glucose (7%), mannose (5%) and xylose (4%) are the constituent
      sugars. Secondary structure analysis indicated that Agp contains 79% alpha
      helices and 21% random coil. Internal sequencing of the tryptic peptides did not
      show homology with the existing proteins in the database (BLAST). Agp at 1 MUg/mL
      induced proliferation of B-cell enriched murine splenocytes and activated
      macrophages in releasing NO and promoted phagocytosis (p < 0.01). RAW 264.7 cells
      produced pro-inflammatory cytokines (IL-12, TNF-alpha and IFN-gamma) at 1 MUg/mL
      Agp (p < 0.01). Deproteinized Agp (dpAgp) failed to elicit activation of murine
      immune cells, whereas deglycosylated Agp (20 kDa; dgAgp) showed compromised
      efficiency. This is the first report of an immunomodulatory protein from ajowan.

PMID- 28493027
TI  - Clinicopathological characteristics of thyroid cancer in the federal state of
      Salzburg.
AB  - OBJECTIVE: The aim of our investigation was to evaluate the clinicopathological
      characteristics and mutation patterns in newly diagnosed cases of thyroid cancer
      in the federal state of Salzburg, Austria, in the year 2013. METHODS: The medical
      records of all patients newly diagnosed with thyroid cancer in 2013 in the
      federal state of Salzburg were retrospectively reviewed. The clinicopathological
      characteristics and mutations of thyroid cancers were analyzed. RESULTS: 63
      patients (mean age: 51.0 years, range: 21-81 years; female 75%, male 25%) were
      identified. 53 patients had papillary (12 follicular variant), 4 patients
      follicular (1 oxyphilic variant), 3 patients medullary, and 3 patients anaplastic
      thyroid cancer. T1 tumors were found in 34 patients (pT1a, 20 patients; pT1b, 14
      patients), T2 tumors in 10 patients, T3 tumors in 16 patients, and T4 tumors in 3
      patients. Lymph node involvement was seen in 15 patients and metastatic disease
      in 1 patient. Mutations of BRAF (B-type Raf kinase) were detected in 23 and
      mutation of NRAS (Neuroblastoma RAS Viral Oncogene Homolog) in 2 papillary
      thyroid cancers. No concomitant mutations of BRAF and NRAS were found.
      CONCLUSION: Females accounted for 75% of the patients with newly diagnosed
      thyroid cancer and the incidence peaked at a younger age than in males. Papillary
      thyroid cancer was the most frequent tumor type, accounting for 84% of the cases.
      A high frequency of T1 tumors and cancers with no lymph node involvement was
      found. Males had a higher proportion of large tumors and more aggressive forms of
      thyroid cancer than females. Mutations (mostly of BRAF) were found in 47% of the
      cases. Neither mutations of KRAS (Kirsten rat sarcoma viral oncogene homologue)
      nor concomitant mutations of BRAF and NRAS were found.

PMID- 28493028
TI  - Every cloud has a silver lining.

PMID- 28493030
TI  - Ambulatory blood pressure response to a bout of HIIT in metabolic syndrome
      patients.
AB  - PURPOSE: The effectiveness of exercise to lower blood pressure may depend on the
      type and intensity of exercise. We study the short-term (i.e., 14-h) effects of a
      bout of high-intensity aerobic interval training (HIIT) on blood pressure in
      metabolic syndrome (MetS) patients. METHODS: Nineteen MetS patients (55.2 +/- 7.3
      years, 6 women) entered the study. Eight of them were normotensive and eleven
      hypertensive according to MetS threshold (>=130 mmHg for SBP and/or >=85 mmHg for
      DBP). In the morning of 3 separated days, they underwent a cycling exercise bout
      of HIIT (>90% of maximal heart rate, ~85% VO2max), or a bout of isocaloric
      moderate-intensity continuous training (MICT; ~70% of maximal heart rate, ~60%
      VO2max), or a control no-exercise trial (REST). After exercise, ambulatory blood
      pressure (ABP; 14 h) was monitored, while subjects continued their habitual daily
      activities wearing a wrist-band activity monitor. RESULTS: No ABP differences
      were found for normotensive subjects. In hypertensive subjects, systolic ABP was
      reduced by 6.1 +/- 2.2 mmHg after HIIT compared to MICT and REST (130.8 +/- 3.9
      vs. 137.4 +/- 5.1 and 136.4 +/- 3.8 mmHg, respectively; p < 0.05). However,
      diastolic ABP was similar in all three trials (77.2 +/- 2.6 vs. 78.0 +/- 2.6 and
      78.9 +/- 2.8 mmHg, respectively). Motion analysis revealed no differences among
      trials during the 14-h. CONCLUSION: This study suggests that the blood pressure
      reducing effect of a bout of exercise is influence by the intensity of exercise.
      A HIIT exercise bout is superior to an equivalent bout of continuous exercise
      when used as a non-pharmacological aid in the treatment of hypertension in MetS.

PMID- 28493029
TI  - Age and sex differences in human skeletal muscle fibrosis markers and
      transforming growth factor-beta signaling.
AB  - PURPOSE: The aim of the study was to determine whether higher fibrosis markers in
      skeletal muscle of older adults are accompanied by increased expression of
      components of the canonical TGF-beta signal transduction pathway. METHODS:
      Fourteen healthy young (21-35 years; 9 males and 5 females) and seventeen older
      (55-75 years; 9 males and 8 females) participants underwent vastus lateralis
      biopsies to determine intramuscular mRNA and protein expression of fibrogenic
      markers and TGF-beta signaling molecules related to TGF-beta1 and myostatin.
      RESULTS: Expression of mRNA encoding the pro-fibrotic factors; axin 2, collagen
      III, beta-catenin and fibronectin, were all significantly higher (all p < 0.05)
      in the older participants (350, 170, 298, and 641%, respectively). Furthermore,
      axin 2 and beta-catenin mRNA were significantly higher in older females than
      older males (p < 0.05). Gene expression of ActRIIB, myostatin, and TGF-beta1 were
      higher in older adults compared to younger adults (all p < 0.05). There was,
      however, no difference in the total protein content of myostatin, myoD or
      myogenin (all p > 0.05), whereas Smad3 protein phosphorylation was 48% lower (p <
      0.05) in muscle from older adults. CONCLUSIONS: Increased abundance of mRNA of
      fibrotic markers was observed in muscle from older adults and was partly
      accompanied by altered abundance of pro-fibrotic ligands in a sex specific
      manner.

PMID- 28493031
TI  - FOXC1 overexpression is a marker of poor response to anthracycline-based adjuvant
      chemotherapy in sporadic triple-negative breast cancer.
AB  - PURPOSE: Because of its aggressive characteristics and poor prognosis, triple
      negative breast cancer (TNBC) has become a hot topic in cancer research.
      Chemotherapy is currently the only treatment for patients with TNBC. The
      transcription factor FOXC1 has been associated with TNBC prognosis, but little is
      known about its effect on chemosensitivity. The aim of this study was to
      investigate the effects of FOXC1 on chemosensitivity. METHODS: A case-control
      study was performed on 25 TNBC patients who experienced relapse and/or
      metastasis. Another 25 patients without relapse or metastasis were randomly
      selected as controls. Medical records were reviewed for relevant information, and
      immunohistochemistry was performed to measure FOXC1 levels. The Kaplan-Meier
      method and Cox analysis were used to analyze differences in disease-free survival
      (DFS) and overall survival (OS). The correlation of FOXC1 expression with
      chemosensitivity was analyzed. Data were analyzed using SPSS 21.0 software, and a
      P value <0.05 was considered to be statistically significant. RESULTS: In 15 of
      22 case patients, FOXC1 was overexpressed, whereas only 8 control patients
      exhibited FOXC1 overexpression (P < 0.05). FOXC1 expression had no correlation
      with pathological indicators. An anthracycline-based regimen was administered to
      21 study patients and 23 control patients. FOXC1 expression was significantly
      associated with a worse DFS (HR 2.62, 95% CI 1.05-6.50, P = 0.038) but presented
      no correlation with OS (HR 2.53, 95% CI 0.76-8.40, P = 0.131) among these 44
      patients. CONCLUSIONS: This study shows that FOXC1 is correlated with
      chemosensitivity to anthracycline and could be used as an indicator of
      chemosensitivity in sporadic TNBC.

PMID- 28493032
TI  - Is there any predictor for hypersensitivity reactions in gynecologic cancer
      patients treated with paclitaxel-based therapy?
AB  - PURPOSE: Recently, generic drugs of paclitaxel have been commonly used mainly by
      economic reasons; however, predictive factors for toxicities are not fully
      determined. Hypersensitivity reaction (HSR) is one of the most important adverse
      events in the paclitaxel-based therapy, and sometimes leads to lethal condition.
      The aim of the study was to identify predictors for HSR in patients treated with
      paclitaxel-based regimens. METHODS: All the patients treated with chemotherapy
      including paclitaxel at our hospital between 1998 and 2013 were retrospectively
      evaluated. Clinicopathological factors of the patients that developed HSR and
      those without HSR were compared, and predictive factors for HSR were identified.
      RESULTS: Among 414 patients enrolled in the study, 26 patients (6.3%) developed
      HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history
      of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1)
      were identified as predictive factors for HSR. There was no significant
      difference in the incidence of HSR between original paclitaxel and generic drug.
      The incidence of HSR was higher as the number of these predictors was
      accumulated. CONCLUSIONS: Three factors were identified as predictive factors for
      HSR: younger age, a history of allergy, and short-course premedication.
      Accumulation of these factors increased the incidence of HSR; however, the use of
      generic drug was not associated HSR in gynecologic cancer patients.

PMID- 28493033
TI  - Is there a genetic anticipation in breast and/or ovarian cancer families with the
      germline c.3481_3491del11 mutation?
AB  - The aim of the current analysis is to evaluate any differences of breast or
      ovarian cancer age at diagnosis between mothers and daughters carrying the
      c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying
      the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who
      reported a first breast or ovarian cancer in their mother carrying the
      c.3481_3491del11 mutation, was identified in 37 different families including
      members with breast and/or ovarian cancer at the Oncology Institute of Lorraine.
      Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers
      daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and
      13 pairs by ovarian cancer. Clinical and genetic data were collected from medical
      files and family pedigrees. Analyses were conducted for each cancer type. We
      investigated an early breast cancer detection effect due to early screening
      programs and also an increased breast tumor aggression. Since major improvements
      in breast cancer clinical management and imaging techniques appeared after 1980,
      we compared the age at breast cancer diagnosis and the age at death in mothers
      and daughters before and after 1980, first, in the group of women including
      mothers and daughters taken together and then in mothers and daughters
      separately. The mean age at breast cancer diagnosis was 45.28 +/- 10.27 years in
      mothers and 39.80 +/- 7.79 years in daughters (p = 0.026). The difference of age
      at ovarian cancer diagnosis in mother-daughter pairs was 8.62 +/- 12.76 years (p
      = 0.032). When considering the group of women including mothers and daughters
      taken together, no significant difference of age at breast cancer diagnosis was
      found between women affected before 1980 and those affected after 1980 (p =
      0.577). However, the age at death increased in these women after 1980 (p =
      0.026). Comparison of age at breast cancer diagnosis in mothers and daughters
      separately, showed that daughters were affected at an earlier age after 1980 (p =
      0.002). Daughters had a poor prognosis and died earlier than mothers after 1980.
      Our results may have reflected genetic anticipation in c.3481_3491del11 mutation
      breast and ovarian cancer families. In order to confirm our findings, a larger
      cohort would provide more precision to the difference of ages at breast or
      ovarian cancer diagnosis between mothers and daughters and more powerful
      statistical analyses. Increased aggression in daughters' tumors compared to those
      of mothers could be also considered as a parameter of genetic anticipation.
      Complete information on tumor profile and proliferation would allow us to study
      genetic anticipation by comparing the tumor phenotypes between mothers and
      daughters in the future.

PMID- 28493034
TI  - [A Japanese in Marburg : Excerpts from the Memories - Jiden - of the Japanese
      Bacteriologist Taichi Kitashima (1870-1956)].
AB  - The heart of this article is the transmission of selected chapters from the
      Japanese bacteriologist Taichi Kitashima's (1870-1956) autobiographical memoirs
      (in Japanese, Jiden) published in 1955, in which Kitashima reports on his stay in
      Marburg in a very personal and subjective way. Like other Japanese physicians of
      his generation, Kitashima spent several years in Germany in order to work with
      the serum researcher Emil von Behring and continued his education there. The
      contact came through Kitashima's teacher Shibasaburo Kitasato, who had worked
      with Behring in Berlin on questions of immunology. The memoir gives insight into
      Behring's laboratory work and his relation to his "subordinates". The editors
      investigate to what extent Kitashima's assessment, made from a distance of fifty
      years, of his stay in Germany as "wasted time" was accurate, given the advantages
      that arose from having been part of a vibrant European scientific community,
      including encounters in the Pasteur Institute in Paris, and why he cultivated his
      contacts with Germany and the Behring family during National Socialism.

PMID- 28493035
TI  - Overlapping MALDI-Mass Spectrometry Imaging for In-Parallel MS and MS/MS Data
      Acquisition without Sacrificing Spatial Resolution.
AB  - Metabolomics experiments require chemical identifications, often through MS/MS
      analysis. In mass spectrometry imaging (MSI), this necessitates running several
      serial tissue sections or using a multiplex data acquisition method. We have
      previously developed a multiplex MSI method to obtain MS and MS/MS data in a
      single experiment to acquire more chemical information in less data acquisition
      time. In this method, each raster step is composed of several spiral steps and
      each spiral step is used for a separate scan event (e.g., MS or MS/MS). One main
      limitation of this method is the loss of spatial resolution as the number of
      spiral steps increases, limiting its applicability for high-spatial resolution
      MSI. In this work, we demonstrate multiplex MS imaging is possible without
      sacrificing spatial resolution by the use of overlapping spiral steps, instead of
      spatially separated spiral steps as used in the previous work. Significant
      amounts of matrix and analytes are still left after multiple spectral
      acquisitions, especially with nanoparticle matrices, so that high quality MS and
      MS/MS data can be obtained on virtually the same tissue spot. This method was
      then applied to visualize metabolites and acquire their MS/MS spectra in maize
      leaf cross-sections at 10 MUm spatial resolution. Graphical Abstract ?.

PMID- 28493036
TI  - Life-cycle of Amblyomma oblongoguttatum (Acari: Ixodidae) under laboratory
      conditions.
AB  - This study evaluated for the first time the life cycle of Amblyomma
      oblongoguttatum in the laboratory. For this purpose, larvae and nymphs were
      exposed to Gallus gallus (chicks), Rattus norvegicus (wistar rat), Calomys
      callosus (vesper mouse), Oryctolagus cuniculus (domestic rabbit), Cavia porcellus
      (guinea pig), and Didelphis albiventris (white-eared opossum). Nymphs were
      exposed to G. gallus, C. callosus, C. porcellus, O. cuniculus, R. norvegicus, and
      Nectomys squamipes (water rat). Adult ticks were exposed to domestic dogs. The
      life-cycle of A. oblongoguttatum in the laboratory could be completed in an
      average period of 188 days, considering prefeeding periods of 25 days for each of
      the parasitic stages. Under laboratory conditions, none of the host species was
      highly suitable for A. oblongoguttatum larvae, since the recovery rates of
      engorged larvae were always <15%, or most of the times <=5%. Similar results were
      obtained for nymphs, with recovery rates of engorged nymphs always <6%. Our
      results, coupled with literature data, suggest that small mammals, especially
      small rodents, do not have an important role in the life-cycle of A.
      oblongoguttatum under field conditions. Domestic dogs showed to be highly
      suitable for the adult stage of A. oblongoguttatum, in agreement with literature
      data that have appointed dogs as important hosts for the adult stage of A.
      oblongoguttatum in South America.

PMID- 28493037
TI  - Toxicity of vegetable oils to the coconut mite Aceria guerreronis and selectivity
      against the predator Neoseiulus baraki.
AB  - The coconut mite, Aceria guerreronis (Acari: Eriophyidae), is a major tropical
      pest of coconut. Here, we assessed the chemical profiles and the potential use of
      babassu, degummed soybean, and coconut oils to control A. guerreronis as well as
      their side-effects on the predatory mite Neoseiulus baraki (Acari: Phytoseiidae),
      a key natural enemy of the coconut mite. Babassu and coconut oils had similar
      fatty acids chemical profiles. All vegetable oils showed toxicity to A.
      guerreronis; degummed soybean oil exhibited the highest toxicity (LC50 = 0.15
      uL/cm2). Although all oils were less toxic to N. baraki, their potential to
      attract/repel this predatory mite differed. Whereas N. baraki females were
      unresponsive to coconut oil at both concentrations (i.e., LC50 and LC99 estimated
      for A. guerreronis), irrespective of exposure period (i.e., 1 or 24 h), the
      babassu oil repelled the predator, independent of exposure period, when applied
      at its LC99 (1.48 uL/cm2). Intriguingly, this oil also exhibited attractiveness
      to N. baraki 24 h after exposure when applied at its LC50 (0.26 uL/cm2). A
      similar attractiveness pattern was recorded 24 h after N. baraki was exposed to
      degummed soybean oil at both concentrations tested (LC50 = 0.15 uL/cm2; LC99 =
      1.39 uL/cm2). However, N. baraki was repelled by degummed soybean oil at its LC50
      after 1 h of exposure. Therefore, the present study demonstrated that all the
      vegetable oils used here had higher toxicity to the coconut mite and considerable
      selectivity to the predator N. baraki, indicating they are promising tools that
      can potentially be included in management programs to control A. guerreronis in
      commercial coconut plantations.

PMID- 28493038
TI  - Perioperative implications of thoracic decortications: a retrospective cohort
      study.
AB  - PURPOSE: An increasing number of thoracic decortications have been performed in
      Manitoba, from five in 2007 to 45 in 2014. The primary objective of this study
      was to define the epidemiology of decortications in Manitoba. The secondary
      objective was to compare patients who underwent decortication due to primary
      infectious vs non-infectious etiology with respect to their perioperative
      outcomes. METHODS: Data for this cohort study were extracted from consecutive
      charts of all adult patients who underwent a decortication in Manitoba from 2007
      2014 inclusive. RESULTS: One hundred ninety-two patients underwent a
      decortication. The most frequent disease processes resulting in a decortication
      were pneumonia (60%), trauma (13%), malignancy (8%), and procedural complications
      (5%). The number of decortications due to complications of pneumonia rose at the
      greatest rate, from three cases in 2007 to 29 cases in 2014. Performing a
      decortication for an infectious vs a non-infectious etiology was associated with
      a higher rate of the composite postoperative outcome of myocardial infarction,
      acute kidney injury, need of vasopressors for > 12 hr, and mechanical ventilation
      for > 48 hr (44.4% vs 24.2%, respectively; relative risk, 1.83; 95% confidence
      interval, 1.1 to 2.9; P = 0.01). CONCLUSION: There has been a ninefold increase
      in decortications over an eight-year period. Potential causes include an increase
      in the incidence of pneumonia, increased organism virulence, host changes, and
      changes in practice patterns. Patients undergoing decortication for infectious
      causes had an increased risk for adverse perioperative outcomes.
      Anesthesiologists need to be aware of the high perioperative morbidity of these
      patients and the potential need for postoperative admission to an intensive care
      unit.

PMID- 28493039
TI  - Complications after surgical treatment of femoral neck fractures in men with
      alcohol dependence syndrome: retrospective register analysis of 154 cases.
AB  - PURPOSE: One-third of hip fractures occur in men. The causes underlying hip
      fractures in men differ from those in women and include alcohol abuse. This
      retrospective register study evaluated the trends and results associated with
      different surgical treatment methods for nondisplaced and displaced femoral neck
      fractures in male patients with alcohol dependence syndrome. METHODS: Men with
      hip fractures were identified from a local district hospital database. Alcohol
      dependence syndrome was identified as a diagnosis in medical records. RESULTS:
      For displaced fractures, implant survival after total hip arthroplasty was
      significantly lower compared to hemiarthroplasty. For nondisplaced fractures,
      implant survival of cannulated screws was significantly lower compared to sliding
      hip screws. Overall patient survival for males with alcohol dependence syndrome
      with hip fracture was 62% at 1 year and 49% at 2 years. Patient survival in this
      population did not differ between displaced and nondisplaced fractures or among
      different surgical methods. CONCLUSION: Patients with alcoholism who had
      documented evidence of alcohol dependence syndrome represented nearly half of
      patients <70 years old with low-energy hip fracture. In patients with
      nondisplaced femoral neck fractures, stability of the internal fixation appeared
      to play a major role in implant survival; sliding hip screws should be considered
      over multiple cannulated screws. In patients with displaced fracture, total hip
      arthroplasty was associated with a significantly higher risk of complications
      leading to revision compared to hemiarthoplasty. LEVEL OF EVIDENCE: Prognostic
      Level III.

PMID- 28493040
TI  - Stability of capsule closure and postoperative anterior knee pain after medial
      parapatellar approach in TKA.
AB  - PURPOSE: Anterior knee pain after total knee arthroplasty (TKA) remains a widely
      discussed postoperative complication. In contrast to sports traumatology, the
      role of the dissected medial patellofemoral ligament (MPFL) using a medial
      parapatellar approach in TKA has not been discussed so far. In the present study,
      it was hypothesized that the attempted repair of the MPFL in TKA by simple
      closure of the joint capsule may not be successful in some cases, causing
      anterior knee pain. Furthermore, it was hypothesized, that the success of repair
      might be influenced by femoral component rotation. METHODS: Forty patients
      received their TKA in a ligament-balanced and forty patients in a conventional
      measured-resection technique. After implantation of the TKA using a medial
      parapatellar approach, two titan clips were attached on both sides of the capsule
      incision. 3 days and 3 months after surgery, the dehiscence of the two clips was
      measured on skyline patella radiographs; additionally patellar tilt, shift, the
      Knee Society Score and the Feller Score were obtained. RESULTS: 48 patients
      showed an increase of capsule dehiscence. Patients with a capsule dehiscence of
      more than 4 mm showed significantly less improvement in the Feller score 3 months
      postoperatively than patients with a capsule dehiscence <=4 mm. Regarding the
      radiological measurements and the clinical outcome, no significant difference
      between the ligament-balanced and the measured-resection group was found.
      CONCLUSIONS: The present results suggest that the successful repair of the MPFL
      after using a medial parapatellar approach in TKA could reduce the high rate of
      postoperative anterior knee pain. Furthermore, the appearance of capsule
      dehiscence and anterior knee pain does not seem to be dependent on the used
      operative technique.

PMID- 28493041
TI  - The sinus tarsi approach in displaced intra-articular calcaneal fractures.
AB  - INTRODUCTION: Although the extended lateral approach is typically considered the
      gold standard of treatment for intra-articular calcaneal fractures, a limited
      lateral approach may be a good alternative in select cases. METHODS: Forty-seven
      consecutive patients with intra-articular calcaneal fractures treated using the
      sinus tarsi approach between March 2010 and April 2015 were retrospectively
      reviewed. The functional outcomes [including arc range of motion, Visual Analog
      Scale (VAS) score, and the American Orthopedic Foot and Ankle Society
      ankle/hindfoot (AOFAS) score], bony outcomes (bony restoration and bony union),
      and complications were evaluated. RESULTS: The mean one-year postoperative VAS
      and AOFAS scores were 0.54 (range 0-3.0), and 94.0 (range 80-100), respectively.
      The VAS and AOFAS scores were correlated with the degree of reduction of the
      posterior facet joint and the amount of Bohler angle restoration. Bony union was
      achieved in every case. The mean union time was 3.2 months (range 3-4 months).
      There were no major soft tissue complications. Three cases of minor soft tissue
      complications healed with no need for subsequent procedures. Painful hardware at
      the posterior calcaneal tuberosity was the most common complication, which
      occurred in seven cases. CONCLUSIONS: The sinus tarsi approach may be a good
      option to treat intra-articular calcaneal fractures in select cases (Sanders type
      II and III) while preventing the major soft tissue complications of the extended
      lateral approach. Level of evidence IV.

PMID- 28493042
TI  - On the stochastic evolution of finite populations.
AB  - This work is a systematic study of discrete Markov chains that are used to
      describe the evolution of a two-types population. Motivated by results valid for
      the well-known Moran (M) and Wright-Fisher (WF) processes, we define a general
      class of Markov chains models which we term the Kimura class. It comprises the
      majority of the models used in population genetics, and we show that many well
      known results valid for M and WF processes are still valid in this class. In all
      Kimura processes, a mutant gene will either fixate or become extinct, and we
      present a necessary and sufficient condition for such processes to have the
      probability of fixation strictly increasing in the initial frequency of mutants.
      This condition implies that there are WF processes with decreasing fixation
      probability-in contradistinction to M processes which always have strictly
      increasing fixation probability. As a by-product, we show that an increasing
      fixation probability defines uniquely an M or WF process which realises it, and
      that any fixation probability with no state having trivial fixation can be
      realised by at least some WF process. These results are extended to a subclass of
      processes that are suitable for describing time-inhomogeneous dynamics. We also
      discuss the traditional identification of frequency dependent fitnesses and pay
      offs, extensively used in evolutionary game theory, the role of weak selection
      when the population is finite, and the relations between jumps in evolutionary
      processes and frequency dependent fitnesses.

PMID- 28493043
TI  - Revisional Surgery After Failed Laparoscopic Sleeve Gastrectomy: Retrospective
      Analysis of Causes, Results, and Technical Considerations.
AB  - BACKGROUND: A failed laparoscopic sleeve gastrectomy (LSG) presents a challenging
      problem for bariatric surgeons. The aim of this study was to evaluate the
      indications, treatment strategies, and surgical outcomes of patients who
      underwent a revisional surgery after a failed LSG. METHODS: This retrospective
      study included the outcomes of 32 patients who required a revisional surgery from
      a series of 500 primary LSGs. The patients' demographic data, indications for
      revisional surgery, perioperative complications, and postoperative outcomes were
      recorded. RESULTS: A total of 500 patients underwent primary LSGs during the
      study period, and 32 of these patients were subjected to revisional bariatric
      surgery after a failed LSG. Weight regain, poor weight loss, and gastroesophageal
      reflux disease (GERD) were the most common causes of revision. A revisional LSG
      (r-LSG) was performed in 23 patients, while 9 patients received a revisional
      laparoscopic Roux-en-Y gastric bypass (r-LRYGB). There were complete sleeve pouch
      dilations in 10 patients. A residual fundus and antrum dilation was detected in 5
      and 8 patients, respectively. The r-LRYGB procedure was performed for GERD
      related symptoms in 6 patients and 3 other patients underwent r-LRYGB due to the
      intake of high-caloric foods. The mean operative time, length of hospital stay,
      and complication rates of revisional surgeries were significantly higher than the
      total cohort. CONCLUSIONS: Although r-LSG and r-LRYGB seem to be safe and
      effective treatment options after a failed LSG, revisional procedures were
      associated with an increased complication rate. Attention to technical details of
      the primary LSG may reduce the revision requirements.

PMID- 28493044
TI  - Postoperative upgrading of prostate cancer in men >=75 years: a propensity score
      matched analysis.
AB  - PURPOSE: Gleason score upgrading should be considered when indicating surgery in
      prostate cancer (PCa) patients. In elderly patients, definitive treatment of low
      risk PCa must be weighed with the risks of overtreatment. Our aim was to evaluate
      rates of Gleason score upgrading in patients >=75 years undergoing radical
      prostatectomy (RP) for localized PCa and to identify predictors associated with
      upgrading. METHODS: 3296 patients undergoing RP were retrospectively evaluated
      and categorized into age groups: <70 years (n = 2971) vs. >=75 years (n = 325).
      We analyzed prostate-specific antigen (PSA), biopsy counts, Gleason score,
      pathologic T- and N-stage, and surgical margin. Propensity score matching was
      performed to compare rates of up- and downgrading on surgical specimen using the
      new five-tier pathologic grading system. Logistic regression was used to identify
      independent predictors of upgrading. RESULTS: Preoperatively, patients >=75 years
      had higher PSA (8.8 vs. 7.3 ng/mL) and lower proportion of grade group 1 (Gleason
      score 6) at biopsy (29.2 vs. 47.9%; both p < 0.001) compared to patients <70
      years. At RP, patients >=75 years were more likely to have extraprostatic disease
      (50 vs. 30%) and lower rates of grade group 1 (14.1 vs. 34.8%; both p < 0.001).
      Postoperative downgrading was similar (15.1 vs. 19.5%). However, patients >=75
      years had higher rates of postoperative upgrading (46.6 vs. 27.9%; p < 0.001).
      Age >=75 years, higher PSA levels at RP, and an increased number of positive
      biopsy cores were associated with upgrading. CONCLUSIONS: Patients >=75 years not
      only demonstrated higher rates of advanced disease but more frequent upgrading on
      RP specimen. Age >=75 years, higher PSA levels at RP, and an increased number of
      positive biopsy cores were predictive for upgrading. The increased risk of
      upgrading should be taken into consideration when discussing optimal treatment
      for this specific cohort.

PMID- 28493045
TI  - Impact of treatment regimen on acute care use during and after adjuvant
      chemotherapy for early-stage breast cancer.
AB  - PURPOSE: The Oncology Care Model was developed, in part, to reduce acute care use
      during the 6 months after chemotherapy initiation. However, little is known about
      the impact of chemotherapy regimen on acute care needs, or about later acute
      care. We sought to assess acute care use over 2 years in patients receiving four
      contemporary adjuvant chemotherapy regimens for breast cancer. METHODS:
      Administrative claims data from a large U.S. commercial insurance database
      (OptumLabs Data Warehouse) were used to retrospectively identify women with early
      stage breast cancer who received adjuvant doxorubicin-cyclophosphamide (AC), AC
      followed or preceded by docetaxel or paclitaxel (AC-T), AC concurrent with
      docetaxel or paclitaxel (TAC), or docetaxel-cyclophosphamide (TC) between 2008
      and 2014. Rates of hospitalizations and emergency department (ED) visits that did
      not lead to hospitalizations were compared during four sequential 6-month periods
      among recipients of these four regimens using negative binomial regression (TC =
      reference). RESULTS: We identified 8621 eligible patients, 87.2% younger than 65.
      Over 6 months, 11.9% were hospitalized and 17.1% had ED visits. Over 24 months,
      17.9% were hospitalized and 28.3% visited the ED. Adjusted rates of
      hospitalizations/100 patients were significantly higher in AC-T and TAC compared
      to TC recipients in the first 6 months (14.9, 21.9, and 11.3, respectively, p <
      0.001). There were no hospitalization rate differences among regimens later. ED
      visit rates did not differ significantly by regimen during any 6-month period.
      CONCLUSION: Higher rates of hospitalizations in recipients of AC-T and TAC were
      restricted to the chemotherapy administration period, and did not persist
      afterwards.

PMID- 28493046
TI  - Trastuzumab uptake and its relation to efficacy in an animal model of HER2
      positive breast cancer brain metastasis.
AB  - PURPOSE: The extent to which efficacy of the HER2 antibody Trastuzumab in brain
      metastases is limited by access of antibody to brain lesions remains a question
      of significant clinical importance. We investigated the uptake and distribution
      of trastuzumab in brain and mammary fat pad grafts of HER2-positive breast cancer
      to evaluate the relationship of these parameters to the anti-tumor activity of
      trastuzumab and trastuzumab emtansine (T-DM1). METHODS: Mouse transgenic breast
      tumor cells expressing human HER2 (Fo2-1282 or Fo5) were used to establish
      intracranial and orthotopic tumors. Tumor uptake and tissue distribution of
      systemically administered 89Zr-trastuzumab or muMAb 4D5 (murine parent of
      trastuzumab) were measured by PET and ELISA. Efficacy of muMAb 4D5, the PI3K/mTOR
      inhibitor GNE-317, and T-DM1 was also assessed. RESULTS: 89Zr-trastuzumab and
      muMAb 4D5 exhibited robust uptake into Fo2-1282 brain tumors, but not normal
      brains. Uptake into brain grafts was similar to mammary grafts. Despite this,
      muMAb 4D5 was less efficacious in brain grafts. Co-administration of muMAb 4D5
      and GNE-317, a brain-penetrant PI3K/mTOR inhibitor, provided longer survival in
      mice with brain lesions than either agent alone. Moreover, T-DM1 increased
      survival in the Fo5 brain metastasis model. CONCLUSIONS: In models of HER2
      positive breast cancer brain metastasis, trastuzumab efficacy does not appear to
      be limited by access to intracranial tumors. Anti-tumor activity improved with
      the addition of a brain-penetrant PI3K/mTOR inhibitor, suggesting that combining
      targeted therapies is a more effective strategy for treating HER2-positive breast
      cancer brain metastases. Survival was also extended in mice with Fo5 brain
      lesions treated with T-DM1.

PMID- 28493047
TI  - Effects of CPAP in patients with obstructive apnoea: is the presence of allergic
      rhinitis relevant?
AB  - PURPOSE: The aim of the study is to compare the effects of continuous positive
      airway pressure (CPAP) on the nasal cavities of patients with obstructive sleep
      apnoea (OSA) and with or without allergic rhinitis (AR/nonAR). METHODS: This
      paper is a prospective, longitudinal study. Thirty-four consecutive CPAP
      treatment-adherent patients with OSA (17 AR and 17 nonAR) were evaluated before
      and 2 months after treatment, by means of clinical (otorhinolaryngological
      symptoms, daytime sleepiness, overall and rhinoconjunctivitis-specific quality of
      life), anatomical (otorhinolaryngological examination), functional (auditory
      function, tubal function, nasal airflow, and mucociliary clearance), and
      biological variables (nasal cytology). No humidifier or anti-allergy medicines
      were used during treatment. RESULTS: Before treatment, patients with AR presented
      a higher score, compared to nonAR in rhinitis symptoms (4.82 +/- 2.53 vs. 0.93 +/
      1.02, p = 0.000), otologic symptoms (2.06 +/- 1.95 vs. 0.44 +/- 0.72, p =
      0.004), cutaneous/ocular symptoms (2.12 +/- 2.17 vs. 0.65 +/- 1.17, p = 0.052),
      immunoglobulin E (181.82 +/- 126.09 vs. 66.13 +/- 97.97, p = 0.004), and nasal
      neutrophils (14.42 +/- 31.94 vs. 0.16 +/- 0.39, p = 0.031). After treatment,
      nonAR and AR groups improved in daytime sleepiness (11.53 +/- 4.60 vs. 7.53 +/-
      2.87, p = 0.000 and 13.76 +/- 4.93 vs. 7.53 +/- 4.41, p = 0.001) respectively and
      increased nasal neutrophil (0.16 +/- 0.39 vs. 5.78 +/- 9.43, p = 0.001 and 14.42
      +/- 31.94 vs. 79.47 +/- 202.08, p = 0.035). The symptoms and quality of life
      improved in patients with AR. NonAR patients, significantly increase nasal
      dryness (1.65 +/- 1.27 vs. 0.00, p = 0.002) and mucociliary clearance times
      (38.59 +/- 24.90 vs. 26.82 +/- 23.18, p = 0.016). CONCLUSIONS: CPAP produces
      inflammation with increased nasal neutrophil levels in AR and nonAR patients.
      Nevertheless, patients with AR observed an improvement in nasal symptoms and
      quality of life, whereas in patients without AR, a relevant worsening of nasal
      dryness and mucociliary transport was observed.

PMID- 28493048
TI  - A Novel omega3-Desaturase in the Deep Sea Giant Tubeworm Riftia pachyptila.
AB  - One paradox of the trophic biochemistry of the deep sea giant tubeworm Riftia
      pachyptila, endemic to hydrothermal vent sites and nourished by polyunsaturated
      fatty acid (PUFA) deficiency chemolitoautotrophic sulfide-oxidizing bacteria, is
      the source of their PUFAs. Biosynthesis of PUFA starts with two precursors C18:2n
      6 and C18:3n-3, which cannot be biosynthesized by most animals due to lack of
      omega6- and omega3-desaturase; thus, C18:2n-6 and C18:3n-3 are generally
      essential fatty acids for animals. Here, we characterized a gene derived from the
      R. pachyptila located by hydrothermal vent, which encoded a novel omega3
      desaturase (Rp3Fad). The gene was identified by searching the R. pachyptila
      transcriptome database using known omega3-desaturases, and its predicted protein
      showed 37-45% identical to omega3-desaturases of fungus and microalgae, and only
      31% identitical to nematode Caenorhabditis elegans omega3-desaturase. Expression
      in yeast Saccharomyces cerevisiae showed that the Rp3Fad could desaturate C18:2n
      6 and C18:3n-6 into C18:3n-3 and C18:4n-3, respectively, displaying a Delta15
      activity similar to plant omega3-desaturase, but it showed no activity towards
      C20 n-6 PUFA substrates, differing from the well-characterized C. elegans omega3
      desaturases. Delta5, Delta6, Delta8, and Delta12 activity were also tested,
      resulting in no corresponding production. The function of omega3-desaturase
      identified in R. pachyptila could produce C18:3n - 3 used in synthesis of n - 3
      series PUFAs, suggesting an adaption to PUFA deficiency environment in deep sea
      hydrothermal vent.

PMID- 28493049
TI  - Identification and Differential Expression of Biomineralization Genes in the
      Mantle of Pearl Oyster Pinctada fucata.
AB  - A series of proteins are involved in shell formation of the pearl oyster Pinctada
      fucata, but the involved mechanisms and the relative expression levels of these
      proteins have not been elucidated. In this study, we sequenced and characterized
      the transcriptome of P. fucata mantle tissue. A total of 100,679 unique
      transcripts were assembled, 43687 Unigenes were annotated, and 48654 CDSs were
      determined. Of these, GO annotated 16353 Unigenes, COG defined 11585 unigenes
      into 25 categories, and KEGG sorted 25053 unigenes into 258 pathways. In total,
      67 biomineralization-related genes were identified, of which 23 genes were newly
      described in P. fucata. These genes included ones that expressed shell matrix
      proteins, regulatory factors, and uncharacterized genes. Differential expression
      of these 67 genes and 9 other biomineralization-related genes was confirmed using
      qPCR. Of the 8 nacreous layer-related genes, MSI60 (774.00) was expressed at a
      much higher level than the others. KRMP2-4 and MSI31 were the most highly
      expressed of the 13 prismatic layer-related genes and KRMP2 was expressed at
      nearly 10000 times of the level of the 18S gene. For genes related to both
      layers, shematrin 2 (3977.84), nacrein (2404.75), PFMG 10 (2113.93), and PFMG 4
      (1015.89) were highly expressed, and ferritin-like protein (877.54) and PFMG 8
      (516.48) were highly expressed among the 16 undefined genes. The expression
      levels of regulation factors were generally low, and the highest level was 324.09
      (EF-hand) and the lowest occurred in the BMP and wnt families. The expression
      levels of the prismatic matrix proteins were much higher than those of nacreous
      ones, consistent with a thicker prismatic layer. MSI60 and nacrein are likely the
      main components of the nacreous layer, and KRMP2-4, MSI31, shematrin 2, and PFMG
      10 gene products are the main components of the prismatic layer. This is the
      first report of transient expression levels of a large number of
      biomineralization-related genes at the same time in mantle tissue of P. fucata.
      These findings provide a novel perspective to understand the molecular mechanisms
      of shell formation and will be beneficial to genetic improvement of P. fucata for
      the production of high-quality pearls as well.

PMID- 28493051
TI  - Erratum to: Genetic analysis of four European huchen (Hucho hucho Linnaeus, 1758)
      broodstocks from Poland, Germany, Slovakia, and Ukraine: implication for
      conservation.

PMID- 28493052
TI  - Development of a colorimetric reverse transcription loop-mediated isothermal
      amplification assay for the detection of Mirafiori lettuce big-vein virus.
AB  - An RT-LAMP assay was developed to detect Mirafiori lettuce big vein virus
      (MiLBVV) and was compared with DAS-ELISA and RT-PCR. All primers were designed on
      the basis of the coat protein gene of the virus. In addition, a novel
      immunocapture (IC) RT-LAMP assay for rapid and easy detection of MiLBVV was
      developed, and factors such as safety, simplicity, cost, user-friendliness and
      safety were compared with those of DAS-ELISA, RT-PCR and RT-LAMP assays. Compared
      with DAS-ELISA and RT-PCR, RT-LAMP and IC-RT-LAMP had higher sensitivity (100
      fold) but similar specificity, with the advantage of a shorter assay time and no
      need for RNA extraction (in IC-RT-LAMP). As RT-LAMP requires only very basic
      instruments and the results can be obtained by visual inspection (using
      GeneFinderTM dye), this technique provides a simple and reliable tool for
      laboratory research.

PMID- 28493050
TI  - Fasudil ameliorates endothelial dysfunction in streptozotocin-induced diabetic
      rats: a possible role of Rho kinase.
AB  - Endothelial dysfunction is a major contributor to the pathogenesis of vascular
      disease in diabetes mellitus and RhoA/Rho-kinase (ROCK) system appears to play a
      crucial role in this setting. The present study was conducted to investigate the
      effect of the selective ROCK inhibitor, fasudil, on diabetes-related endothelial
      dysfunction and elucidated its underlying mechanism(s). Diabetes was induced by a
      single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), and fasudil
      (5 mg/kg per day) was orally administered for 8 weeks. Our results showed that
      fasudil administration attenuated the increased activity/expression of ROCK
      (627.5 +/- 27 vs. 247.8 +/- 19.1) and the NADPH oxidase subunits, NOX2 and
      p47phox, in diabetic rat aorta. Fasudil could reduce the elevated tumor necrosis
      factor (TNF)-alpha (70.2 +/- 14.1 vs. 25.3 +/- 5.2) and transforming growth
      factor (TGF-beta) levels and restored the deficit in antioxidant level of the
      diabetic aorta. Additionally, fasudil markedly improved the endothelial
      dysfunction in the diabetic aorta (73.8 +/- 8.1 vs. 47.42 +/- 8.69) and corrected
      the dysregulated endothelial nitric oxide (eNOS) expression. In conclusion, the
      present study demonstrates that fasudil effectively ameliorates the endothelial
      dysfunction in STZ-induced diabetic rats through inhibition of the Rho/ROCK
      pathway and thereby reducing the TNF-alpha-mediated NADPH oxidase activation.

PMID- 28493053
TI  - Regulation of cathepsin D activity by the FTLD protein progranulin.

PMID- 28493054
TI  - The Dynamics of a SEIR-SIRC Antigenic Drift Influenza Model.
AB  - We consider the dynamics of an influenza model with antigenic drift mechanism.
      Antigenic drift is an antigen mutation on the skin surface of the influenza virus
      that do not produce a new virus strain. The mutation produces the same virus but
      with slightly different antigens that cannot be recognized by the immune
      receptors formed by the previous infection. There are some type of influenza that
      involve the interaction between two populations such as human and animal. In this
      paper, we construct an influenza model with antigenic drift mechanism on the
      human population that has interaction with the animal population. The animal
      population is assumed to follow the SEIR epidemic model. Our model is motivated
      by the fact that some of the influenza cases in human come from the animal such
      as the swine and the avian. The transmission parameter that shows number of
      contact between the susceptible human and the infectious animals are important to
      study. The parameter plays an important role to detect the cycle of infection of
      the disease. The other important parameters are the seasonality degree, which
      shows the pathogen appearance and disappearance via annual migration, and the
      infection rate on the human population. We employ the bifurcation theory to
      analyze the behavior of the system and to detect the cycle of infection types
      when the parameters values are varied.

PMID- 28493055
TI  - A Patient-Specific Anisotropic Diffusion Model for Brain Tumour Spread.
AB  - Gliomas are primary brain tumours arising from the glial cells of the nervous
      system. The diffuse nature of spread, coupled with proximity to critical brain
      structures, makes treatment a challenge. Pathological analysis confirms that the
      extent of glioma spread exceeds the extent of the grossly visible mass, seen on
      conventional magnetic resonance imaging (MRI) scans. Gliomas show faster spread
      along white matter tracts than in grey matter, leading to irregular patterns of
      spread. We propose a mathematical model based on Diffusion Tensor Imaging, a new
      MRI imaging technique that offers a methodology to delineate the major white
      matter tracts in the brain. We apply the anisotropic diffusion model of Painter
      and Hillen (J Thoer Biol 323:25-39, 2013) to data from 10 patients with gliomas.
      Moreover, we compare the anisotropic model to the state-of-the-art Proliferation
      Infiltration (PI) model of Swanson et al. (Cell Prolif 33:317-329, 2000). We find
      that the anisotropic model offers a slight improvement over the standard PI
      model. For tumours with low anisotropy, the predictions of the two models are
      virtually identical, but for patients whose tumours show higher anisotropy, the
      results differ. We also suggest using the data from the contralateral hemisphere
      to further improve the model fit. Finally, we discuss the potential use of this
      model in clinical treatment planning.

PMID- 28493056
TI  - Non-Vitamin K Oral Anticoagulants for Stroke Prevention in Special Populations
      with Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke
      or systemic embolism compared with normal sinus rhythm. These strokes may
      efficiently be prevented in patients with risk factors using oral anticoagulant
      therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist
      oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa
      inhibitors). Owing to their specific risk profiles, some AF populations may have
      increased risks of both thromboembolic and bleeding events. These AF patients may
      be denied oral anticoagulants, whilst evidence shows that the absolute benefits
      of oral anticoagulants are greatest in patients at highest risk. NOACs are an
      alternative to VKAs to prevent stroke in patients with "non-valvular AF", and
      NOACs may offer a greater net clinical benefit compared with VKAs, particularly
      in these high-risk patients. Physicians have to learn how to use these drugs
      optimally in specific settings. We review concrete clinical scenarios for which
      practical answers are currently proposed for use of NOACs based on available
      evidence for patients with kidney disease, elderly patients, women, patients with
      diabetes, patients with low or high body weight, and those with valve disease.

PMID- 28493057
TI  - Absorptance determinations on multicellular tissues.
AB  - The analysis of the variation of the capacity and efficiency of photosynthetic
      tissues to collect solar energy is fundamental to understand the differences
      among species in their ability to transform this energy into organic molecules.
      This analysis may also help to understand natural changes in species distribution
      and/or abundance, and differences in species ability to colonize contrasting
      light environments or respond to environmental changes. Unfortunately, the
      challenge that optical determinations on highly dispersive samples represent has
      strongly limited the progression of this analysis on multicellular tissues,
      limiting our knowledge of the role that optical properties of photosynthetic
      tissues may play in the optimization of photosynthesis and growth of benthonic
      primary producers. The aim of this study is to stimulate the use of optical tools
      in marine eco-physiology, offering a succinct description of the more convenient
      tools and also solutions to resolve the more common technical difficulties that
      arise while performing optical determinations on highly dispersive samples. Our
      study focuses on two-dimensional (2D-) parameters: absorptance, transmittance,
      and reflectance, and illustrates with correct and incorrect examples, specific
      problems and their respective solutions. We also offer a general view of the
      broad variation in light absorption shown by photosynthetic structures of marine
      primary producers, and its low association with pigment content. The ecological
      and evolutionary functional implications of this variability deserve to be
      investigated across different taxa, populations, and marine environments.

PMID- 28493058
TI  - C-terminal cleavage of the LH1 alpha-polypeptide in the Sr2+-cultured
      Thermochromatium tepidum.
AB  - The light-harvesting 1 reaction center (LH1-RC) complex in the thermophilic
      purple sulfur bacterium Thermochromatium (Tch.) tepidum binds Ca ions as
      cofactors, and Ca-binding is largely involved in its characteristic Q y
      absorption at 915 nm and enhanced thermostability. Ca2+ can be biosynthetically
      replaced by Sr2+ in growing cultures of Tch. tepidum. However, the resulting Sr2+
      substituted LH1-RC complexes in such cells do not display the absorption maximum
      and thermostability of those from Ca2+-grown cells, signaling that inherent
      structural differences exist in the LH1 complexes between the Ca2+- and Sr2+
      cultured cells. In this study, we examined the effects of the biosynthetic Sr2+
      substitution and limited proteolysis on the spectral properties and
      thermostability of the Tch. tepidum LH1-RC complex. Preferential truncation of
      two consecutive, positively charged Lys residues at the C-terminus of the LH1
      alpha-polypeptide was observed for the Sr2+-cultured cells. A proportion of the
      truncated LH1 alpha-polypeptide increased during repeated subculturing in the
      Sr2+-substituted medium. This result suggests that the truncation is a
      biochemical adaptation to reduce the electrostatic interactions and/or steric
      repulsion at the C-terminus when Sr2+ substitutes for Ca2+ in the LH1 complex.
      Limited proteolysis of the native Ca2+-LH1 complex with lysyl protease revealed
      selective truncations at the Lys residues in both C- and N-terminal extensions of
      the alpha- and beta-polypeptides. The spectral properties and thermostability of
      the partially digested native LH1-RC complexes were similar to those of the
      biosynthetically Sr2+-substituted LH1-RC complexes in their Ca2+-bound forms.
      Based on these findings, we propose that the C-terminal domain of the LH1 alpha
      polypeptide plays important roles in retaining proper structure and function of
      the LH1-RC complex in Tch. tepidum.

PMID- 28493059
TI  - Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of
      the adult human pancreas.
AB  - Organic anion-transporting polypeptides (OATPs) are membrane proteins that
      mediate cellular uptake of structurally diverse endogenous and exogenous
      compounds, including bile salts, thyroid and sex hormones, pharmacological
      agents, and toxins. Roles of OATPs in human liver are well established. Our
      recent report suggested the presence of the hepatic transporter OATP1B3 in human
      beta cells. The aim of this study was to better characterize cellular
      localization and interindividual variation in OATP1B3 expression in human adult
      islets as a function of age, sex, and pancreatic disease, and to assess the
      expression of other OATPs. High transcript levels of OATP1B3, OATP2B1, OATP1A2,
      but not OATP1B1 were observed in isolated human adult islets. While OATP1B3
      protein expression was variable, the carrier co-localized more frequently with
      glucagon-positive alpha cells than insulin-positive beta cells in islets of
      normal pancreatic tissues from ten subjects using dual immunostaining. Moreover,
      OATP1B3 co-staining with endocrine cells was two- to three-fold higher in older
      (>=60 years) than younger (<60 years) subjects. In comparison, in a subset of
      three individuals, OATP2B1 was primarily found in beta cells, suggesting a
      distinct expression pattern for OATP1B3 and OATP2B1 in islets. Abundant OATP1B3
      staining was also observed in islet as well as ductal cells of diseased tissues
      of patients with pancreatitis or pancreatic adenocarcinoma. Considering the
      abundance of key OATP carriers in beta and alpha cells, potential implications of
      OATP transport in islet cell function may be suggested. Future studies are needed
      to gain insights into their specific endocrine roles as well as pharmacological
      relevance.

PMID- 28493060
TI  - Synthetic Turf Fields, Crumb Rubber, and Alleged Cancer Risk.
AB  - Most synthetic turf fields have crumb rubber interspersed among the simulated
      grass fibers to reduce athletic injuries by allowing users to turn and slide more
      readily as they play sports or exercise on the fields. Recently, the crumbs have
      been implicated in causing cancer in adolescents and young adults who use the
      fields, particularly lymphoma and primarily in soccer goalkeepers. This concern
      has led to the initiation of large-scale studies by local and federal governments
      that are expected to take years to complete. Meanwhile, should the existing
      synthetic turf fields with crumb rubber be avoided? What should parents, players,
      coaches, school administrators, and playground developers do? What should sports
      medicine specialists and other health professionals recommend? Use grass fields
      when weather and field conditions permit? Exercise indoors? Three basic premises
      regarding the nature of the reported cancers, the latency of exposure to
      environmental causes of cancer to the development of clinically detectable
      cancer, and the rarity of environmental causation of cancer in children,
      adolescents, and young adults suggest otherwise.

PMID- 28493061
TI  - Chronotype, Physical Activity, and Sport Performance: A Systematic Review.
AB  - BACKGROUND: Many variables related to sport have been shown to have circadian
      rhythms. Chronotype is the expression of circadian rhythmicity in an individual,
      and three categories of chronotype are defined: morning types (M-types), evening
      types (E-types), and neither types (N-types). M-types show earlier peaks of
      several psychophysiological variables during the day than E-types. The effect of
      chronotype on athletic performance has not been extensively investigated.
      OBJECTIVE: The objective of the present review was to study the effect of
      chronotype on athletic performance and the psychophysiological responses to
      physical activity. METHODS: The present review adheres to the PRISMA (Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines.
      We searched PubMed, Scopus, and Web of Science for scientific papers using the
      keywords "chronotype", "circadian typology", "morningness", and "eveningness" in
      combination with each of the words "sport", "performance", and "athletic."
      Relevant reference lists were inspected. We limited the search results to peer
      reviewed papers published in English from 1985 to 2015. RESULTS: Ten papers met
      our inclusion criteria. Rating of perceived exertion and fatigue scores in
      relation to athletic performances are influenced by chronotype: M-types perceived
      less effort when performing a submaximal physical task in the morning than did N-
      and E-types. In addition, M-types generally showed better athletic performances,
      as measured by race times, in the morning than did N- and E-types. Other results
      concerning chronotype effect on physiological responses to physical activity were
      not always consistent: heterogeneous samples and different kinds of physical
      activity could partially explain these discrepancies. CONCLUSIONS: Sports
      trainers and coaches should take into account the influence of both the time of
      day and chronotype effect when scheduling training sessions into specific time
      periods.

PMID- 28493062
TI  - Comment on: "Are Prepubertal Children Metabolically Comparable to Well-Trained
      Adult Endurance Athletes?"

PMID- 28493063
TI  - Authors' Reply to Dotan and Falk: "Are Prepubertal Children Metabolically
      Comparable to Well-Trained Adult Endurance Athletes?"

PMID- 28493064
TI  - Evidence-Based Prerequisites and Precursors of Athletic Talent: A Review.
AB  - Extensive findings related to nature and nurture in determining athletic talent
      (AT) have been reviewed. Available data demonstrate the important contribution of
      hereditary factors as well as the crucial importance of environmental
      prerequisites for identifying and developing AT. Recent publications provide
      examples of contemporary approaches intended to solve the problem of how to
      discover and nurture AT. A number of cross-sectional and longitudinal studies
      highlighted possibilities of revealing a predisposition to certain sports among
      youthful prospects, but were unable to predict attainment of world-class status.
      Data pertaining to Olympic champions indicate that their superiority compared
      with other elite athletes is determined by high intrinsic motivation,
      determination, dedication, persistence, and creativity. These salient
      manifestations of personality could be successfully recognized even in the
      initial stages of their preparation, where exceptionally gifted individuals
      manifested high learnability and a high rate of athletic improvement. Moreover,
      future champions were characterized by an exceptional attitude to training and a
      willingness to perform more voluminous and high-quality training routines.
      Exceptionally talented athletes in endurance, power, and combat sports attained
      world-class status after 4-7 years of specialized preparation, accumulating 3000
      7000 h of purposeful training. This stands in contradiction to Ericsson's theory
      of deliberate practice and the 10-year rule. In contrast, Olympic artistic
      gymnastics champions attained world-class status following an average of 9.7
      years of specialized preparation, accumulating an average of 8918 h of
      specialized training. Apparently, the theory of 10,000 h of deliberate practice
      and the 10-year rule are selectively applicable to highly coordinative esthetic
      sports but not to general preparation trends in endurance, power, and combat
      sports.

PMID- 28493065
TI  - Healthcare Utilization by Older Age Groups in Northern States of Peninsular
      Malaysia: The Role of Predisposing, Enabling and Need Factors.
AB  - Determining factors that affect healthcare utilization by the elderly is vital
      for the health system to be more responsive in providing care to this vulnerable
      group. The main objective of this paper is to identify the effect of the
      predisposing, enabling, and need factors on doctor visits and in-patient care for
      the elderly residing in the northern region of Malaysia. A multistage cluster
      sampling was used in selecting the sample for the study. A total of 1414
      respondents aged 60 and over were interviewed face-to-face using a structured
      questionnaire. A probit model was used in estimating the utilization equations.
      At a significance level of 0.05, except for age, all predisposing and enabling
      factors were not statistically significant in affecting the doctor visits. On the
      other hand, being a male, smoker, medical insurance holder or had not actively
      involved in social interaction within the reference period increases the
      likelihood of being in-patient. Health-related variables remain the most
      significant factors that determine healthcare utilization, including both doctor
      visits and in-patient stays, in the area of study, which suggests that government
      policies to improve population health may influence the level of healthcare use
      in the future.

PMID- 28493066
TI  - Cognition and balance control: does processing of explicit contextual cues of
      impending perturbations modulate automatic postural responses?
AB  - Processing of predictive contextual cues of an impending perturbation is thought
      to induce adaptive postural responses. Cueing in previous research has been
      provided through repeated perturbations with a constant foreperiod. This
      experimental strategy confounds explicit predictive cueing with adaptation and
      non-specific properties of temporal cueing. Two experiments were performed to
      assess those factors separately. To perturb upright balance, the base of support
      was suddenly displaced backwards in three amplitudes: 5, 10 and 15 cm. In
      Experiment 1, we tested the effect of cueing the amplitude of the impending
      postural perturbation by means of visual signals, and the effect of adaptation to
      repeated exposures by comparing block versus random sequences of perturbation. In
      Experiment 2, we evaluated separately the effects of cueing the characteristics
      of an impending balance perturbation and cueing the timing of perturbation onset.
      Results from Experiment 1 showed that the block sequence of perturbations led to
      increased stability of automatic postural responses, and modulation of magnitude
      and onset latency of muscular responses. Results from Experiment 2 showed that
      only the condition cueing timing of platform translation onset led to increased
      balance stability and modulation of onset latency of muscular responses.
      Conversely, cueing platform displacement amplitude failed to induce any effects
      on automatic postural responses in both experiments. Our findings support the
      interpretation of improved postural responses via optimized sensorimotor
      processes, at the same time that cast doubt on the notion that cognitive
      processing of explicit contextual cues advancing the magnitude of an impending
      perturbation can preset adaptive postural responses.

PMID- 28493068
TI  - Cathepsin S increases tau oligomer formation through limited cleavage, but only
      IL-6, not cathespin S serum levels correlate with disease severity in the
      neurodegenerative tauopathy progressive supranuclear palsy.
AB  - Limited cleavage promotes the aggregation propensity of protein tau in
      neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of
      patients suffering from tauopathies such as Alzheimer's disease (AD).
      Furthermore, CatS serum levels correlate with survival in the elderly. The
      current study investigates whether limited cleavage by CatS promotes tau
      aggregation, and whether CatS serum levels may correlate with disease severity in
      tauopathies. Oligomer formation of fluorescently labeled protein tau was
      monitored by single particle fluorescence spectroscopy after coincubation with
      CatS. Tau cleavage patterns were investigated by SDS-PAGE. For serum analyses,
      samples were collected from 42 patients with probable progressive supranuclear
      palsy (PSP) according to NINDS-PSP criteria. Disease severity was assessed by PSP
      rating scale (PSP-RS), PSP staging system (PSP-S) and Schwab and England
      Activities of Daily Living (SEADL). CatS, cystatin C (CysC) and interleukin 6 (IL
      6) serum levels were determined by ELISA, ECLIA and turbidimetry, respectively.
      SDS-PAGE demonstrated a distinct cleavage pattern of protein tau after
      coincubation with CatS. Furthermore, tau oligomer formation was increased 2.4
      fold (p < 0.05) after limited cleavage. Serum CatS and CysC levels did not
      correlate with disease severity in PSP. Of note, IL-6 correlated with PSP-S (r =
      0.41; 95% CI 0.11-0.65; p = 0.008), SEADL (r = -0.37; 95% CI -0.61 to -0.06; p =
      0.017) and the history and gait/midline subdomains of the PSP-RS. While CatS
      facilitates tau aggregation in vitro, serum levels of CatS appear not to
      correlate with disease severity. The observed correlation of IL-6 with disease
      severity warrants further investigation of inflammatory markers in PSP.

PMID- 28493067
TI  - Visuotactile interaction even in far sagittal space in older adults with
      decreased gait and balance functions.
AB  - Spatial proximity of signals from different sensory modalities is known to be a
      crucial factor in facilitating efficient multisensory processing in young adults.
      However, recent studies have demonstrated that older adults exhibit strong
      visuotactile interactions even when the visual stimuli were presented in a
      spatially disparate position from a tactile stimulus. This suggests that
      visuotactile peripersonal space differs between older and younger adults. In the
      present study, we investigated to what extent peripersonal space expands in the
      sagittal direction and whether this expansion was linked to the decline in
      sensorimotor functions in older adults. Vibrotactile stimuli were delivered
      either to the left or right index finger, while visual stimuli were presented at
      a distance of 5 cm (near), 37.5 cm (middle), or 70 cm (far) from each finger. The
      participants had to respond rapidly to a randomized sequence of unimodal (visual
      or tactile) and simultaneous visuotactile targets (i.e., a redundant target
      paradigm). Sensorimotor functions were independently assessed by the Timed Up and
      Go (TUG) and postural stability tests. Results showed that reaction times to the
      visuotactile bimodal stimuli were significantly faster than those to the unimodal
      stimuli, irrespective of age group [younger adults: 22.0 +/- 0.6 years, older
      adults: 75.0 +/- 3.3 years (mean +/- SD)] and target distance. Of importance, a
      race model analysis revealed that the co-activation model (i.e., visuotactile
      multisensory integrative process) is supported in the far condition especially
      for older adults with relatively poor performance on the TUG or postural
      stability tests. These results suggest that aging can change visuotactile
      peripersonal space and that it may be closely linked to declines in sensorimotor
      functions related to gait and balance in older adults.

PMID- 28493070
TI  - Quality of routine diagnostic abdominal images generated from a novel detector
      based spectral CT scanner: a technical report on a phantom and clinical study.
AB  - PURPOSE: To evaluate the image quality of routine diagnostic images generated
      from a novel detector-based spectral detector CT (SDCT) and compare it with CT
      images obtained from a conventional scanner with an energy-integrating detector
      (Brilliance iCT), Routine diagnostic (conventional/polyenergetic) images are non
      material-specific images that resemble single-energy images obtained at the same
      radiation, METHODS: ACR guideline-based phantom evaluations were performed on
      both SDCT and iCT for CT adult body protocol. Retrospective analysis was
      performed on 50 abdominal CT scans from each scanner. Identical ROIs were placed
      at multiple locations in the abdomen and attenuation, noise, SNR, and CNR were
      measured. Subjective image quality analysis on a 5-point Likert scale was
      performed by 2 readers for enhancement, noise, and image quality. RESULTS: On
      phantom studies, SDCT images met the ACR requirements for CT number and
      deviation, CNR and effective radiation dose. In patients, the qualitative scores
      were significantly higher for the SDCT than the iCT, including enhancement (4.79
      +/- 0.38 vs. 4.60 +/- 0.51, p = 0.005), noise (4.63 +/- 0.42 vs. 4.29 +/- 0.50, p
      = 0.000), and quality (4.85 +/- 0.32, vs. 4.57 +/- 0.50, p = 0.000). The SNR was
      higher in SDCT than iCT for liver (7.4 +/- 4.2 vs. 7.2 +/- 5.3, p = 0.662),
      spleen (8.6 +/- 4.1 vs. 7.4 +/- 3.5, p = 0.152), kidney (11.1 +/- 6.3 vs. 8.7 +/-
      5.0, p = 0.033), pancreas (6.90 +/- 3.45 vs 6.11 +/- 2.64, p = 0.303), aorta
      (14.2 +/- 6.2 vs. 11.0 +/- 4.9, p = 0.007), but was slightly lower in lumbar
      vertebra (7.7 +/- 4.2 vs. 7.8 +/- 4.5, p = 0.937). The CNR of the SDCT was also
      higher than iCT for all abdominal organs. CONCLUSION: Image quality of routine
      diagnostic images from the SDCT is comparable to images of a conventional CT
      scanner with energy-integrating detectors, making it suitable for diagnostic
      purposes.

PMID- 28493069
TI  - Comparison of molecular marker expression in early zebrafish brain development
      following chronic ethanol or morpholino treatment.
AB  - This study was undertaken to ascertain whether defined markers of early zebrafish
      brain development are affected by chronic ethanol exposure or morpholino
      knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors,
      four signaling molecules that are suggested to be ethanol sensitive. Zebrafish
      embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha,
      aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze
      otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early
      brain development. Our results showed that pax6a mRNA expression was decreased in
      eye, forebrain, and hindbrain of both chronic ethanol exposed and select MO
      treatments. Epha4a expression in rhombomere R1 boundary was decreased in chronic
      ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants, but largely
      unaffected in agrin and shha morphants. Ectopic pax6a and epha4a expression in
      midbrain was only found in fgf8a morphants. These results suggest that while
      chronic ethanol induces obvious morphological change in brain architecture, many
      molecular markers of these brain structures are relatively unaffected by ethanol
      exposure.

PMID- 28493071
TI  - Nontraumatic large bowel perforation: spectrum of etiologies and CT findings.
AB  - Large bowel perforation is an abdominal emergency that results from a wide range
      of etiologies. Computed tomography is the most reliable modality in detecting the
      site of large bowel perforation. The diagnosis is made by identifying direct CT
      findings such as extraluminal gas or contrast and discontinuity along the bowel
      wall. Indirect CT findings can help support the diagnosis, and include bowel wall
      thickening, pericolic fat stranding, abnormal bowel wall enhancement, abscess,
      and a feculent collection adjacent to the bowel. Common etiologies that cause
      large bowel perforation are colon cancer, foreign body aspiration, stercoral
      colitis, diverticulitis, ischemia, inflammatory and infectious colitides, and
      various iatrogenic causes. Recognizing a large bowel perforation on CT can be
      difficult at times, and there are various entities that may be misinterpreted as
      a colonic perforation. The purpose of this article is to outline the MDCT
      technique used for evaluation of suspected colorectal perforation, discuss
      relevant imaging findings, review common etiologies, and point out potential
      pitfalls in making the diagnosis of large bowel perforation.

PMID- 28493072
TI  - Arterial injury during transcatheter arterial chemoembolization for
      hepatocellular carcinoma: predictors of risk and outcome.
AB  - PURPOSE: To investigate clinical features and results of follow-up in patients
      with arterial injury during transcatheter arterial chemoembolization (TACE) for
      hepatocellular carcinoma. METHODS: From 2005 to 2015, 2219 TACE procedures were
      performed in 906 patients in our hospital. Iatrogenic arterial injury occurred
      during 38 TACE procedures (sessions) in 35 patients (24 men, 11 women; mean age
      71.8 years). The incidence of arterial injury was 1.7%. We evaluated the
      characteristics of arterial injury, and evaluated the risk factors for incomplete
      recanalization of the injured artery at follow-up angiography conducted after 1
      11 months (mean 102.5 days). RESULTS: Iatrogenic arterial injury was caused by
      the microcatheter in 34 of 38 cases (86.8%). There were 15 cases (39.5%) in which
      the replaced hepatic artery or the extrahepatic artery was the parasitic supply.
      Extravasation occurred in five cases. In 36 of 38 cases, follow-up angiography
      was performed. We divided 36 cases into two groups: complete reopening (n = 24)
      and non-complete reopening (n = 12). The two groups were compared regarding the
      factors associated with incomplete recanalization of the injured artery at follow
      up. Injury length >3 cm (p = 0.0002) and proximal arterial injury (proximal to
      the segmental artery; p = 0.03) were significant risk factors for non-complete
      reopening of the injured artery. CONCLUSION: Iatrogenic arterial injury
      frequently occurred in the extrahepatic artery or replaced hepatic artery.
      Recanalization rate of arterial injury was high; however, injury length >3 cm and
      proximal arterial injury were risk factors for non-complete reopening of the
      injured artery.

PMID- 28493073
TI  - Gastroduodenal and pancreatic surgeries: indications, surgical techniques, and
      imaging features.
AB  - This review article focuses on gastroduodenal and pancreatic surgeries with the
      goal of identifying radiologic findings that translate to important surgical
      considerations. The topics covered include partial gastrectomy with
      reconstruction techniques, total gastrectomy, pancreaticoduodenectomy, and
      pancreaticojejunostomy. Indications, contraindications, surgical techniques, and
      postoperative imaging are described within each of these topics. Knowledge of
      these surgical techniques is extremely helpful for the interpreting radiologists
      to identify expected postoperative anatomy and related complications that would
      remain clinically relevant to our surgical colleagues and direct timely patient
      management.

PMID- 28493074
TI  - Corrective osteotomies of the lower limb show a low intra- and perioperative
      complication rate-an analysis of 1003 patients.
AB  - PURPOSE: The purpose of corrective osteotomies in posttraumatic and congenital
      deformities is anatomic limb reconstruction and joint preservation. The aim of
      the present study was to analyse intra- and perioperative complications of
      osteotomies in the lower limb. METHODS: One thousand and three unselected and
      prospectively registered osteotomies of the long bones of the lower limb,
      performed between 1995 and 2013, were analysed. In 435 women and 568 men (mean
      age 39.8 years), 478 correction osteotomies were performed femoral and 525
      tibial; 696 osteotomies were performed using the oscillating saw, 42 using the
      Gigli saw and 265 using drill hole/chisel osteoclasis. A total of 869 deformities
      were corrected in the acute setting and 134 were corrected continuously via
      callotaxis. RESULTS: Seventeen (1.7%) major complications requiring revision
      surgeries were detected: 4 arterial injuries, 2 haematomas, 4 compartment
      syndromes and 7 deep wound infections. All vascular injuries 4 (0.7%) occurred in
      osteotomies around the knee (n = 563). Nineteen (1.9%) minor complications could
      be managed by conservative means: 3 (0.3%) deep vein thromboses and 16 (1.6%)
      superficial wound infections. No osteomyelitis, pulmonary embolism or death
      occurred. Gigli saw osteotomy was stained by a higher infection rate. In male
      patients (p = 0.02), posttraumatic deformities (ns) and continuous procedures (p
      = 0.025) have a higher risk of superficial infections. No further risks were
      detected for age, weight, smoking habit and anatomic level of surgery.
      CONCLUSION: Osteotomies around the knee show a very low complication rate. Less
      aggressive oscillating saws, saw blades and drills are recommended. Vascular
      injuries, compartment syndromes and deep infections are limb-threatening
      emergencies demanding fast and determined interventions. LEVEL OF EVIDENCE:
      Prospective cohort study, Level III.

PMID- 28493075
TI  - MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related
      growth factors in human gastric cancer.
AB  - BACKGROUND: We recently reported that miR-1 was one of the most significantly
      downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome
      Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in
      gastric carcinogenesis. METHODS: We measured miR-1 expression in human GC cell
      lines and 90 paired primary GC samples, and analyzed the association of its
      status with clinicopathological features. The effect of miR-1 on GC cells was
      evaluated by proliferation and migration assay. To identify the target genes of
      miR-1, bioinformatic analysis and protein array analysis were performed.
      Moreover, the regulation mechanism of miR-1 with regard to these predicted
      targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and
      endothelial cell tube formation. The putative binding site of miR-1 on target
      genes was assessed by a reporter assay. RESULTS: Expression of miR-1 was
      obviously decreased in GC cell lines and primary tissues. Patients with low miR-1
      expression had significantly shorter overall survival compared with those with
      high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited
      proliferation, migration, and tube formation of endothelial cells by suppressing
      expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1
      (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an
      increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low
      malignancy GC cells. CONCLUSIONS: MiR-1 acts as a tumor suppressor by inhibiting
      angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1
      not only promotes cellular proliferation and migration of GC cells, but may
      activates proangiogenesis signaling and stimulates the proliferation and
      migration of endothelial cells, indicating the possibility of new strategies for
      GC therapy.

PMID- 28493076
TI  - Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in
      discrete inflammatory arthropathies.
AB  - OBJECTIVE: Extracellular vesicles (EVs) are subcellular signalosomes. Although
      characteristic EV production is associated with numerous physiological and
      pathological conditions, the effect of blood-derived EVs on bone homeostasis is
      unknown. Herein we evaluated the role of circulating EVs on human
      osteoclastogenesis. METHODS: Blood samples from healthy volunteers, rheumatoid
      arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based
      EV sub-fractions were isolated by gravity-driven filtration and differential
      centrifugation. To investigate the properties of EV samples, resistive pulse
      sensing technique, transmission electron microscopy, flow cytometry and western
      blot were performed. CD14+ monocytes were separated from PBMCs, and stimulated
      with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7
      days, the cells were fixed and stained for tartrate-resistant acid phosphatase
      and counted. RESULTS: EVs isolated by size-based sub-fractions were characterized
      as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n =
      12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p <
      0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory
      effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14+ cells
      were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)
      derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in
      all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect.
      CONCLUSIONS: Our data suggest that blood-derived EXOs are novel regulators of the
      human osteoclastogenesis and may offer discrete effector function in distinct
      inflammatory arthropathies.

PMID- 28493077
TI  - Lung Protective Effects of Low-Volume Resuscitation and Pharmacologic Treatment
      of Swine Subjected to Polytrauma and Hemorrhagic Shock.
AB  - Hemorrhage is a common cause of death in the battlefield. Valproic acid (VPA) has
      been associated with improved outcomes in multiple models of trauma, when
      combined with isotonic fluid resuscitation. However, isotonic fluid administered
      in this setting is logistically impractical and may be associated with
      complications. In this study, we sought to evaluate the feasibility and
      immunologic impact of combining VPA treatment with low-volume hypertonic saline
      (HTS). In vivo: female Yorkshire swine were subjected to hemorrhage (40% total
      blood volume) and polytrauma (rib fracture and delayed liver injury). Animals
      were kept in shock for 30 minutes and resuscitated with (1) normal saline (NS, 3*
      hemorrhaged volume), (2) HTS (7.5% saline, 4 mL/kg), or (3) HTS + VPA (4 mg/kg;
      150 mg/kg; n = 3/cohort). After 18 hours of observation, animals were euthanized
      and the lungs evaluated for acute injury and expression of myeloperoxidase (MPO)
      and caveolin-1 (Cav-1). In vitro: human umbilical vein endothelial cells (HUVECs)
      were exposed to anoxic conditions (5% CO2, 95% N2) for 16 hours in (1)
      normosmotic, (2) hyperosmotic (400 mOsm), or (3) hyperosmotic + VPA (4 mM) media.
      Immunohistochemistry and Western blots were performed to determine Cav-1
      expression. Lungs from VPA-treated animals demonstrated decreased acute injury,
      MPO expression, and endothelial expression of Cav-1 when compared to lungs from
      animals resuscitated with NS or HTS alone. Similarly, HUVECs cultured in
      hyperosmotic media containing VPA demonstrated decreased expression of Cav-1.
      This study demonstrates that combined treatment with VPA and HTS is a viable
      strategy in hemorrhagic shock and polytrauma. Attenuation of lung injury
      following VPA treatment may be related to modulation of the inflammatory
      response.

PMID- 28493078
TI  - The 5-HT3 Receptor Antagonist Ondansetron Attenuates Pancreatic Injury in
      Cerulein-Induced Acute Pancreatitis Model.
AB  - The 5-hydroxytryptamine-3 receptor (5-HT3R) antagonist ondansetron has been
      clinically approved as an anti-emetic agent. Recent findings indicate that
      ondansetron has anti-inflammatory properties. The aim of the present study was to
      assess the therapeutic action of ondansetron in cerulein-induced acute
      pancreatitis model. Male-BALB/c mice were used in the present study. Acute
      pancreatitis was induced by an hourly injection of cerulein. Ondansetron was
      administered subcutaneously at a dose of 3 mg/kg. The messenger RNA (mRNA)
      expression of 5-HT3 R in pancreatic tissue was assessed with RT-PCR. Plasma
      amylase, lipase, and interleukin (IL)-6 levels were evaluated. Pancreatic injury
      was histopathologically graded, and myeloperoxidase (MPO)-positive cells were
      counted. 5-HT3R mRNA was expressed in the pancreas. In acute pancreatitis model
      mice, amylase, lipase, and IL-6 levels were significantly increased in the blood.
      With ondansetron treatment, these levels were significantly decreased.
      Histopathological evaluation revealed that ondansetron attenuated the
      inflammatory damage in acute pancreatitis. The number of infiltrated neutrophils
      stained by MPO was decreased by ondansetron treatment. In summary, the 5-HT3R
      antagonist ondansetron attenuated pancreatic injury through its anti-inflammatory
      action. These findings suggest that ondansetron may potentially be of use for
      therapy of acute pancreatitis.

PMID- 28493079
TI  - TLR2 Regulates Allergic Airway Inflammation and Autophagy Through PI3K/Akt
      Signaling Pathway.
AB  - Toll-like receptors (TLRs) are innate pattern recognition receptors that play a
      critical role in allergic inflammation, yet their contribution to autophagy in
      asthma remains poorly defined. Here, we investigate the role of Toll-like
      receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt)
      pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild
      type (WT) and TLR2-knockout (TLR2-/-) C57BL/6 mice were ovalbumin-sensitized and
      ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of
      TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell
      hyperplasia, and increased mucus production were observed. The number of
      inflammatory cells and interleukin-13 (IL-13) levels increased, while interferon
      gamma (IFN-gamma) levels decreased in bronchoalveolar lavage fluid. Expression of
      PI3K, phospho-Akt, Beclin-1 and LC3-II was enhanced significantly. These changes
      were mitigated dose-dependently in 3-methyl adenine-treated mice. In contrast,
      similar but weaker changes were found in ovalbumin-challenged TLR2-/- mice, and
      the changes were not significantly attenuated by 3-methyl adenine treatment.
      These results indicate that TLR2 confers a pivotal role in allergic airway
      inflammation via regulating the PI3K/Akt signaling pathway-related autophagy in
      mice.

PMID- 28493080
TI  - Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS
      Gene Expression.
AB  - Postoperative ileus is a common complication after intra-abdominal surgery.
      Nitric oxide produced by macrophages in the inflamed gastrointestinal tract plays
      a crucial role in the pathogeny of postoperative ileus. Honokiol, extracted from
      the bark of Magnolia spp., is a natural compound with a biphenolic structure. In
      the present study, we examined the effect of honokiol on postoperative ileus and
      discussed its site of action. Postoperative ileus model mice were generated by
      surgical intestinal manipulation. Mice were administered honokiol (10 mg kg-1,
      per os) 1 h before and after intestinal manipulation. Gastrointestinal transit,
      leukocyte infiltration, and messenger RNA (mRNA) expression of inflammatory
      mediators were measured in postoperative ileus model mice with or without
      honokiol. We also investigated the inflammatory effect of honokiol in
      lipopolysaccharide-stimulated peritoneal macrophages. Gastrointestinal transit
      was delayed in postoperative ileus model mice and honokiol recovered the impaired
      transit. Honokiol significantly inhibited leukocyte infiltration and upregulation
      of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6) and inducible nitric oxide synthase in the ileal muscle layer of
      postoperative ileus model mice. In peritoneal macrophages activated by
      lipopolysaccharide, honokiol significantly inhibited the upregulated mRNA
      expression of proinflammatory cytokines and inducible nitric oxide synthase.
      Honokiol significantly recovered gastrointestinal dysmotility and inhibited
      intestinal inflammation in postoperative ileus. Moreover, honokiol was suggested
      to have effects on macrophages, namely, inhibiting mRNA expression of
      proinflammatory cytokines and inducible nitric oxide synthase. Taken together,
      honokiol represents a potential novel therapeutic agent for postoperative ileus.

PMID- 28493081
TI  - Regulation of iNOS-Derived ROS Generation by HSP90 and Cav-1 in Porcine
      Reproductive and Respiratory Syndrome Virus-Infected Swine Lung Injury.
AB  - In the lungs, endothelial nitric oxide synthase (eNOS) is usually expressed in
      endothelial cells and inducible nitric oxide synthase (iNOS) is mainly expressed
      in alveolar macrophages and epithelial cells. Both eNOS and iNOS are involved in
      lung inflammation. While they play several roles in lung inflammation formation
      and resolution, their expression and activity are also regulated by inflammatory
      factors. Their expression relationship in virus infection-induced lung injury is
      not well addressed. In this report, we analyzed expression of both eNOS and iNOS,
      the production of nitric oxide (NO) and reactive oxygen species (ROS), and
      expression of their associated regulatory proteins, heat shock protein 90 (HSP90)
      and caveolin-1 (Cav-1), in a swine lung injury model induced by porcine
      reproductive and respiratory syndrome virus (PRRSV) infection. The combination of
      upregulation of iNOS and downregulation of eNOS was observed in both natural and
      experimental PRRSV-infected lungs, while the combination is much enhanced in
      natural infected lungs. While NO production is much reduced in both infections,
      ROS was enhanced only in natural infected lungs. Moreover, HSP90 is increased in
      both natural and experimental infection and less Cav-1 expressed was observed
      only in the natural PRRSV-infected lungs. Therefore, the increased ROS generation
      is likely due to the increased iNOS and its unbalanced regulation by HSP90 and
      Cav-1, and it also likely causes higher endothelial dysfunction in clinical PRRSV
      infected lungs.

PMID- 28493082
TI  - Electro-Acupuncture at Zusanli Acupoint (ST36) Suppresses Inflammation in
      Allergic Contact Dermatitis Via Triggering Local IL-10 Production and Inhibiting
      p38 MAPK Activation.
AB  - Acupuncture has shown beneficial effect in the treatment of multiple dermatologic
      conditions including dermatitis, pruritus, urticaria, and hyperhidrosis; however,
      the detailed mechanisms are still kept unclear. This study aimed to investigate
      if electro-acupuncture (EA) treatment prevents 2,4-dinitrofluorobenzene (DNFB)
      induced allergic contact dermatitis (ACD) in rats and explore its underlying
      mechanisms. ACD was induced by sensitizing and challenging with DNFB topically.
      Rats were treated daily following bilateral subcutaneous stimulation of EA at
      Zusanli acupoint (ST36) for 1 week. Ear swelling and serum IgE levels were
      measured. The ear biopsies were obtained for histology. Inflammatory cytokines on
      the dermatological ear and local acupoint tissue were assayed. Spleen lymphocytes
      and the homogenized supernatant of local acupuncture area were used to co-culture
      for flow cytology and immune analysis, respectively. EA treatment at ST36 notably
      inhibited ear swelling and inflammatory cell infiltration on DNFB-induced ACD. EA
      also decreased serum IgE concentrations and alleviated the production of
      inflammatory cytokines in dermatological ear. Additionally, EA treatment
      attenuated the percentage of CD4+IFN-gamma+ and CD4+IL-4+ T cells associated with
      ACD. Interestingly, secretion of interleukin (IL)-10 in the local acupoint tissue
      following EA stimulation was increased and showed suppressive function when co
      cultured with the spleen lymphocytes from DNFB group. Lastly, EA treatment
      demonstrably suppressed p38 MAPK activation in DNFB-treated rats. Our findings
      suggest that EA treatment at ST36 may ameliorate inflammation associated with
      DNFB-induced ACD via triggering local IL-10 production and inhibiting p38 MAPK
      activation, which provide an alternative and promising therapy for ACD.

PMID- 28493083
TI  - Protective Effects of Acupuncture in Cardiopulmonary Bypass-Induced Lung Injury
      in Rats.
AB  - Acute lung injury caused by cardiopulmonary bypass (CPB) increases the mortality
      after cardiac surgery. Our previous clinical study suggested that
      electroacupuncture (EAc) has a protective effect during CPB, but the mechanism
      was unclear. So, we design this study to investigate the effects of EAc on CPB
      induced lung injury and the underlying mechanism. Male Sprague Dawley rats were
      randomly divided into control, CPB, and CPB + EAc groups. A lung injury model was
      created by CPB surgery to serve as the CPB group, and EAc (2/100 Hz) was used
      before CPB in the CPB + EAc group. Lung tissue was collected at 0.5, 1, and 2 h
      after CPB. Pulmonary malondialdehyde (MDA) concentrations as well as superoxide
      dismutase (SOD), myeloperoxidase (MPO), and caspase-3 activity were determined. c
      Jun N-terminal kinase (JNK), ERK, p38 and cleaved caspase 3 in the lung were
      analyzed by western blotting. A549 cells were treated by rat serum from the CPB
      and CPB + EAc groups, and cleaved caspase-3 activity was detected by fluorescent
      immunohistochemistry. CPB significantly increased the MPO activity, MDA content,
      apoptosis, caspase-3 activity, and phosphorylated p38 but decreased SOD activity
      compared with the control group. EAc significantly increased SOD activity at 0.5
      and 2 h (p < 0.01 vs CPB) and reduced CPB-induced histological changes, MPO
      activity at 1 and 2 h (p < 0.05 vs CPB), MDA content at 2 h (p < 0.05 vs CPB),
      caspase-3 activity at 1 h (p < 0.05 vs CPB), and phosphorylated p38 and JNK at
      0.5 h after CPB. The serum from the CPB group increased more positive staining
      cells of cleaved caspase-3 than that from the CPB + EAc group. EAc reversed the
      CPB-induced lung inflammation, oxidative damage, and apoptosis; the mechanism may
      involve decreased phosphorylation of p38 along with caspase-3 activity and
      activation.

PMID- 28493084
TI  - Combined intracoronary 2D-3D optical coherence tomography and intravascular
      ultrasound imaging in left main severe stent malapposition.

PMID- 28493085
TI  - Pericardial Effusion and Cardiac Tamponade in the New Millennium.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review current approaches to
      the diagnosis and treatment of pericardial effusions and cardiac tamponade.
      RECENT FINDINGS: Recent recommendations from the American Society of
      Echocardiography and the European Society of Cardiology have refined our
      approaches to the patient with pericardial effusion and cardiac tamponade, but
      significant knowledge gaps remain. New diagnostic and triage strategies have been
      proposed, and recent data have advanced our ability to assess the presence and
      size of a pericardial effusion, assess its hemodynamic impact, and establish its
      cause. Despite these recent findings, there is a paucity of evidence-based data
      to guide the management of pericardial effusion and cardiac tamponade. While the
      first-line function of echocardiography in managing these disorders is
      unquestioned, there are increasing niche roles for multimodality imaging.

PMID- 28493086
TI  - Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma
      elasticum: 4-year results from the PIXEL study in France.
AB  - PURPOSE: To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg
      in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma
      elasticum (PXE) in a real-world setting. METHODS: A descriptive, observational,
      multicenter study in a retrospective and prospective cohort was conducted in
      France that included patients who had received at least one injection of
      ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV
      secondary to PXE. Eligible patients were identified by review of medical records
      or during routine consultations. The main objectives were to describe patient
      characteristics, assess changes in best-corrected visual acuity [VA, Early
      Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and
      reasons for ranibizumab treatment and overall safety. RESULTS: Of the 72 enrolled
      patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [+/-standard
      deviation (SD)] age was 59.6 (+/-8.3) years. The mean VA was 64.6 letters at the
      first ranibizumab injection, which was maintained at the 1-year follow-up (64.7
      letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4
      years, the proportion of eyes with VA gain of >=15 letters was 3/19 (15.8%) and
      stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (+/-SD)
      annual number of ranibizumab injections was 4.1 (+/-4.0), lower in the second
      versus first year. The most common reason for ranibizumab treatment was
      progression of neovascular activity (42.9%). No deaths or new safety findings
      were reported. CONCLUSIONS: In patients with CNV secondary to PXE, ranibizumab
      0.5 mg resulted in stable VA over 4 years with a limited number of injections.
      Safety findings were consistent with the established safety profile of
      ranibizumab.

PMID- 28493087
TI  - Ciliary body thickness changes after preoperative anti-inflammatory treatment in
      rhegmatogenous retinal detachment complicated by choroidal detachment.
AB  - BACKGROUND: The literature is scant on the state of the ciliary body, its role in
      the development of rhegmatogenous retinal detachment (RRD) complicated by
      choroidal detachment (CD), and on ciliary body changes following the treatment
      aimed at resolving concomitant inflammation and choroidal attachment. This study
      assesses the anatomical position and thickness of the ciliary body and
      investigates the ciliary body changes after anti-inflammatory pre-vitrectomy
      treatment in RRD complicated by CD. METHODS: Forty-nine patients (49 eyes) with
      RRD complicated by CD underwent standard ophthalmological examination (including
      visual acuity assessment, biomicroscopy, ophthalmoscopy, and ocular tonometry)
      and ultrasound biomicroscopy of the ciliary body, choroid, and retina both before
      and following anti-inflammatory pre-vitrectomy treatment. RESULTS: At baseline,
      all subject eyes had ciliary body edema and detachment extending into the
      choroid. Ultrasonographic ciliary features included ciliary body edema and
      disorganization of the supraciliary layer of the pars plana, which was evident by
      the presence of multiple small oblique fibers. In all subject eyes, the treatment
      resulted in reattachment of the choroid and the ciliary body as well as a
      reduction in ciliary body edema (total mean ciliary thickness reduced from 0.83
      (0.09) to 0.65 (0.09) mm, with a difference of 0.18 (0.07) mm, P < 0.001).
      CONCLUSIONS: Preoperative anti-inflammatory treatment in RRD complicated by CD
      results in restoration of the anatomical position of the ciliary body and a
      statistically significant reduction in ciliary body edema.

PMID- 28493088
TI  - Establishing a Framework for a Natural Area Taxonomy.
AB  - The identification of areas of endemism is essential in building an area
      classification, but plays little role in how natural areas are discovered. Rather
      area monophyly, derived from cladistics, is essential in the discovery of natural
      area classifications or area taxonomy. We propose Area Taxonomy to be a new sub
      discipline of historical biogeography, one that can be revised and debated, and
      which has its own area nomenclature. Separately to area taxonomy, we outline how
      natural areas may be discovered by transcribing the concepts of homology and
      monophyly from biological systematics to historical biogeography, in the form of
      area homologues, area homologies and area monophyly.

PMID- 28493090
TI  - [Impaired recognition of environmental sounds in patients with dementia : I can
      hear but I do not understand].
AB  - BACKGROUND: Impairment of central auditory processing is a well-known symptom of
      neurodegenerative dementia; however, whilst numerous studies have examined verbal
      processing impairment, to date few have attempted to describe impairments of non
      verbal, environmental sound recognition in patients with dementia. As these
      impairments may have direct implications on patient support and care, such
      studies are urgently necessary. AIM OF THE STUDY: The aim of the study was to
      determine whether the recognition of meaningful environmental sounds is impaired
      in patients with mild or early stage neurodegenerative dementia. PATIENTS AND
      METHODS: We developed a test of non-verbal sound recognition consisting of 16
      sound sequences from the familiar and unfamiliar environments. We included 18
      patients with mild cognitive impairment and mild dementia caused by Alzheimer's
      disease and frontotemporal dementia, as well as 20 cognitively healthy controls.
      RESULTS: Patients and controls were given the test of recognizing 16 meaningful
      sounds from the familiar and unfamiliar environments. Patients with dementia
      performed significantly worse in comparison to cognitively healthy controls.
      Whilst healthy controls correctly recognized on average 12.1 +/- 2.2 out of 16
      sounds, cognitively impaired patients recognized 9.2 +/- 2.5. Correlation
      analysis showed that the mini mental state examination (MMSE) scores were
      positively correlated with the number of correctly recognized sounds (MMSE: r =
      0.556, p = 0.017). DISCUSSION: The fact that even in mild stages of Alzheimer's
      disease or frontotemporal dementia patients either do not recognize or
      misinterpret environmental sounds must be taken into consideration not only in
      everyday life but in particular when patients need to leave their familiar living
      environment, whether temporarily (e. g. hospitalization) or permanently (e. g.
      nursing home admission).

PMID- 28493091
TI  - [Violence against the elderly in domestic care settings : Short profile of an
      interdisciplinary research project].
AB  - Most elderly people wish to remain and be cared for in their own home.
      Approximately 1.38 million people in Germany are cared for without professional
      support. However, domestic care by relatives can be a risk factor for violence
      against the elderly. This research project deals with the issue from a legal and
      social sciences perspective. The aim of the project is to develop a regulatory
      framework providing aid-oriented prevention and intervention in the family care
      of vulnerable elderly people by public agencies and courts. Firstly, empirical
      data on the situation in family care will be analyzed; secondly, the existing
      legal framework will be examined. In a third step, recommendations for
      legislation and administration will be developed in collaboration with
      practitioners. Initial findings show that, although various support, advice, and
      training services exist, the situation at home is not always safe. There is a
      lack of legal regulation on the issue of abuse in the family care setting,
      especially compared with German legislation on child protection. Thus, the legal
      framework should reinforce the prevention of care problems by giving more
      efficient support to carers and permitting legal intervention in the case of
      abuse. However, at the same time, the proposed legislation should take into
      account the importance of the individual's right to self-determination.

PMID- 28493093
TI  - Insights from mathematical modeling for convection-enhanced intraputamenal
      delivery of GDNF.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potential therapy for
      Parkinson's disease (PD) promoting survival and functional recovery of
      dopaminergic neurons when delivered to the degenerated striatum. To study the
      aspects of intraputamenal delivery of GDNF, a mathematical model of recombinant
      methionyl human GDNF (r-metHuGDNF) convection in the human putamen has been
      developed. The convection-enhanced delivery infusions of r-metHuGDNF were
      simulated at rates up to 5 MUL/min. The high-rate infusions (>=1 MUL/min) permit
      rapid and uniform distribution of drug with up to 75% of the distribution volume
      having a concentration within 5% of the infusate concentration. No relevant
      differences in distribution at infusion rates of 3 and 5 MUL/min were found. The
      patterns of GDNF distribution were analyzed in relation to the anatomy of the
      posterior dorsal putamen, and a cylindrical shape was found to be preferable
      considering risks of target overflow. A magnetic resonance (MR) tracer Gd-DTPA
      (Magnevist(r)) was evaluated as a surrogate in clinical studies, and the most
      accurate prediction of GDNF distribution was calculated immediately after
      infusion. The clearance of GDNF from the striatum is confirmed to be slow, with a
      half-life of ca. 19 h.

PMID- 28493094
TI  - New minimally invasive surgical approach for excision of left atrial myxoma.
AB  - A novel minimally invasive technique for left atrial myxoma surgery involving a
      combination of mini-sternotomy and restricted left atrial dome incision is
      described. Surgery is performed through a mini-J sternotomy at third intercostal
      space and a standard aorto-right atrial cannulation. Exposure of cardiac mass is
      obtained by a restricted incision of the left atrial dome which provides
      excellent view of the entire interatrial septum. Base of the tumor base is
      clearly visualized making the en-bloc excision extremely easy. Three cases were
      successfully treated with this technique and discharged with mild analgesic
      requirements. The limited invasiveness and the avoidance of wide incisions in the
      heart chambers are points of strength of this approach and allow to overcome the
      limitations of the currently used interatrial groove or transeptal approaches, as
      scarce visualization of the septum and site of tumor attachment and risk of
      conduction disturbances or traumatic injury to the mass.

PMID- 28493095
TI  - Can a Saddle Nose Deformity of Granulomatosis with Polyangiitis be Repaired?

PMID- 28493096
TI  - Multiple malignant epithelioid mesotheliomas of the liver and greater omentum: a
      case report and review of the literature.
AB  - BACKGROUND: Malignant mesothelioma commonly arises from the pleura, but can also
      arise from the peritoneum, pericardium, and tunica vaginalis testis. However,
      malignant mesothelioma of the liver is extremely rare and coexistence with
      malignant mesothelioma of the greater omentum has not been described in the
      literature. In this case report, we present a case of multiple malignant
      mesothelioma of the liver and greater omentum. CASE PRESENTATION: A 36-year-old
      woman was admitted to our hospital for the evaluation of an elastic hard mass in
      the right upper abdomen. Abdominal contrast computed tomography showed a cystic
      mass measuring 13 * 14 * 11 cm in the right liver lobe with enhanced mural
      nodule. Abnormal accumulation was identified in the liver and lower abdominal
      area on 18F-fluorodeoxyglucose positron emission tomography. The patient
      underwent hepatectomy of the posterior segment and partial resection of the
      omentum. The final pathological diagnosis was low-grade multiple malignant
      epithelioid mesothelioma based on characteristic immunohistochemical findings. As
      of 6 months postoperatively, the patient has shown no disease recurrence.
      CONCLUSIONS: We present the first case of a 36-year-old woman with multiple
      malignant mesothelioma of the liver and greater omentum.

PMID- 28493097
TI  - Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor:
      a case of a rare malignancy.
AB  - BACKGROUND: A gastric adenosquamous carcinoma (ASC) that produces granulocyte
      colony stimulating factor (G-CSF) is an uncommon malignancy with a poor
      prognosis. Due to the rarity of this lesion, a standard treatment for the disease
      has not been established. CASE PRESENTATION: We describe a case of a 66-year-old
      male with a G-CSF-producing gastric ASC who presented with severe anemia and
      leukocytosis. A radical resection was performed, followed by a course of adjuvant
      chemotherapy. Histopathologic examination revealed that the tumor consisted of
      areas of both squamous cell carcinoma and adenocarcinoma. Immunohistochemical
      staining with an anti-G-CSF antibody was also positive. He was started on
      adjuvant capecitabine and oxaliplatin (CapeOX) 6 weeks after surgery. The patient
      stopped treatment after 3 months due to his own preference. Eight months
      following surgery, the patient was found to have diffuse lymph node, liver, and
      peritoneal metastases. CONCLUSIONS: G-CSF-producing gastric ASC is a rare and
      aggressive tumor. Because patients are usually diagnosed at an advanced stage,
      multidisciplinary evaluation and innovative treatments are needed. The rarity of
      this disease, with its aggressive features, poses a significant challenge in its
      treatment. In this brief case report, we summarize the management and outcomes of
      G-CSF-producing gastric ASC.

PMID- 28493098
TI  - Personalized Therapeutics and Pharmacogenomics: Integral to Personalized Health
      Care.

PMID- 28493099
TI  - Anti-Inflammatory Therapeutic Effect of Adiponectin Gene Delivery Using a
      Polymeric Carrier in an Acute Lung Injury Model.
AB  - PURPOSE: Adiponectin (APN) is an adipokine with anti-inflammatory and
      cytoprotective effects. In this study, the therapeutic effect of APN gene
      delivery using a polymeric carrier was evaluated in an acute lung injury (ALI)
      model. METHODS: Polyethylenimine (2 kDa, PEI2K), PEI25K (25 kDa), polyamidoamine
      (generation 2, PAMG2), dexamethasone-conjugated PEI2k (PEI2K-Dexa), and
      dexamethasone-conjugated PAMG2 (PAMG2-Dexa) were evaluated in vitro and in vivo
      as gene carriers. Formation of plasmid DNA (pDNA)/carrier complexes was confirmed
      by gel retardation and heparin competition assays. Delivery efficiency was
      measured by a luciferase assay and fluorescence microscopy. In an ALI animal
      model, pAPN/carrier complexes were delivered by intratracheal administration.
      Therapeutic effects were evaluated by cytokine assays and hematoxylin and eosin
      (H&E) staining. RESULTS: Gel retardation assays showed that PEI2K-Dexa and PAMG2
      Dexa formed complexes with pDNA. In L2 lung epithelial cells, PAMG2-Dexa yielded
      higher transfection efficiency than PEI2K, PAMG2, PEI25K, lipofectamine, and
      PEI2K-Dexa. In vivo experiments showed that PAMG2-Dexa delivered DNA more
      efficiently to lung tissue than PEI2K-Dexa and PEI25K. Delivery of pAPN/PAMG2
      Dexa complexes upregulated APN expression in the lungs of mice with ALI. As a
      result, the levels of pro-inflammatory cytokines such as TNF-alpha and IL-1beta
      were decreased. H&E staining showed that inflammation in the lungs of mice with
      ALI was reduced by delivery of the APN gene. CONCLUSION: Delivery of the APN gene
      using PAMG2-Dexa reduced inflammation in the lungs of mice with ALI. The APN gene
      could be a useful tool in the development of gene therapy for ALI.

PMID- 28493100
TI  - Characterization of Temperature Profiles in Skin and Transdermal Delivery System
      When Exposed to Temperature Gradients In Vivo and In Vitro.
AB  - PURPOSE: Performance of a transdermal delivery system (TDS) can be affected by
      exposure to elevated temperature, which can lead to unintended safety issues.
      This study investigated TDS and skin temperatures and their relationship in vivo,
      characterized the effective thermal resistance of skin, and identified the in
      vitro diffusion cell conditions that would correlate with in vivo observations.
      METHODS: Experiments were performed in humans and in Franz diffusion cells with
      human cadaver skin to record skin and TDS temperatures at room temperature and
      with exposure to a heat flux. Skin temperatures were regulated with two methods:
      a heating lamp in vivo and in vitro, or thermostatic control of the receiver
      chamber in vitro. RESULTS: In vivo basal skin temperatures beneath TDS at
      different anatomical sites were not statistically different. The maximum
      tolerable skin surface temperature was approximately 42-43 degrees C in vivo. The
      temperature difference between skin surface and TDS surface increased with
      increasing temperature, or with increasing TDS thermal resistance in vivo and in
      vitro. CONCLUSIONS: Based on the effective thermal resistance of skin in vivo and
      in vitro, the heating lamp method is an adequate in vitro method. However, the in
      vitro-in vivo correlation of temperature could be affected by the thermal
      boundary layer in the receiver chamber.

PMID- 28493101
TI  - The German East-West Mortality Difference: Two Crossovers Driven by Smoking.
AB  - Before the fall of the Berlin Wall, mortality was considerably higher in the
      former East Germany than in West Germany. The gap narrowed rapidly after German
      reunification. The convergence was particularly strong for women, to the point
      that Eastern women aged 50-69 now have lower mortality despite lower incomes and
      worse overall living conditions. Prior research has shown that lower smoking
      rates among East German female cohorts born in the 1940s and 1950s were a major
      contributor to this crossover. However, after 1990, smoking behavior changed
      dramatically, with higher smoking intensity observed among women in the eastern
      part of Germany. We forecast the impact of this changing smoking behavior on East
      West mortality differences and find that the higher smoking rates among younger
      East German cohorts will reverse their contemporary mortality advantage.
      Mortality forecasting methods that do not account for smoking would, perhaps
      misleadingly, forecast a growing mortality advantage for East German women.
      Experience from other countries shows that smoking can be effectively reduced by
      strict anti-smoking policies. Instead, East Germany is becoming an example
      warning of the consequences of weakening anti-smoking policies and changing
      behavioral norms.

PMID- 28493102
TI  - MEN2 Syndrome-Related Medullary Thyroid Carcinoma with Focal Tyrosine Hydroxylase
      Expression: Does It Represent a Hybrid Cellular Phenotype or Functional State of
      Tumor Cells?

PMID- 28493103
TI  - Cellulose Derivatives Enhanced Stability of Alginate-Based Beads Loaded with
      Lactobacillus plantarum LAB12 against Low pH, High Temperature and Prolonged
      Storage.
AB  - The susceptibility of probiotics to low pH and high temperature has limited their
      use as nutraceuticals. In this study, enhanced protection of probiotics via
      microencapsulation was achieved. Lactobacillus plantarum LAB12 were immobilised
      within polymeric matrix comprised of alginate (Alg) with supplementation of
      cellulose derivatives (methylcellulose (MC), sodium carboxymethyl cellulose
      (NaCMC) or hydroxypropyl methylcellulose (HPMC)). L. plantarum LAB12 encapsulated
      in Alg-HPMC(1.0) and Alg-MC(1.0) elicited improved survivability (91%) in
      simulated gastric conditions and facilitated maximal release (~100%) in simulated
      intestinal condition. Alg-HPMC(1.0) and Alg-MC(1.0) significantly reduced (P <
      0.05) the viability loss of LAB12 (viability loss <7%) when compared to Alg alone
      (viability loss <13%) under extreme temperatures (75 and 90  degrees C). Four
      week storage of encapsulated LAB12 at 4  degrees C yielded viable counts >7 log
      CFU g-1. Alg-MC and Alg-HPMC improved the survival of LAB12 against simulated
      gastric condition (9.24 and 9.55 log CFU g-1, respectively), temperature up to 90
      degrees C (9.54 and 9.86 log CFU g-1, respectively) and 4-week of storage at 4 
      degrees C (8.61 and 9.23 log CFU g-1, respectively) with sustained release of
      probiotic in intestinal condition (>9 log CFU g-1). These findings strongly
      suggest the potential of cellulose derivatives supplemented Alg bead as
      protective micro-transport for probiotic strains. They can be safely incorporated
      into new functional food or nutraceutical products.

PMID- 28493104
TI  - Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN
      gene.
AB  - Hypomyelinating leukodystrophies are a group of neurodevelopmental disorders that
      affect proper formation of the myelin sheath in the central nervous system. They
      are characterized by developmental delay, hypotonia, spasticity, and variable
      intellectual disability. We used whole exome analysis to study the molecular
      basis of hypomyelinating leukodystrophy in two sibs from a consanguineous family.
      A homozygous mutation, c.3068+5G>A, was identified in the ATRN gene, with the
      consequent insertion of an intronic sequence into the patients' cDNA and a
      predicted premature termination of the ATRN polypeptide. ATRN encodes Attractin,
      which was previously shown to play a critical role in central myelination.
      Several spontaneous ATRN rodent mutants exhibited impaired myelination which was
      attributed to oxidative stress and accelerated apoptosis. ATRN can now be added
      to the growing list of genes associated with hypomyelinating leukodystrophy. The
      disease seems to be confined to the CNS; however, given the young age of our
      patients, longer follow-up may be required.

PMID- 28493105
TI  - Association between cardiovascular disease risk scores and subclinical
      atherosclerosis prevalence in non-elderly adult patients from Argentina.
AB  - The goal of our study was to use statistical analysis to try to associate
      cardiovascular disease (CVD) risk scores and the observed prevalence of
      subclinical atherosclerosis (SA) in a non-elderly adult local population. An
      observational cross-sectional study was carried out (143 male and 131 female) on
      non-elderly adults (20-59 years). CVD risk scores included Framingham Risk Scores
      for 10-year hard (FRS 10 H), 30-year lipid hard or CVD (FRS 30 L H or FRS 30 L
      CVD), 30 year-body mass index hard or CVD (FRS 30 BMI H or FRS 30 BMI CVD) and
      Pooled Cohort Risk Equations for either 10 years (PCE 10) or lifetime (PCE LT).
      The Carotid Ultrasound (CU) study was performed and the Coronary Artery Calcium
      (CAC) score were obtained to assess SA. The Receiving Operating Characteristic
      (ROC) curve analysis followed by Youden's index was used to evaluate and adjust
      the stratification of CVD risk scores. SA was detected in 32.4% of individuals.
      The risk scores that showed the biggest areas under the ROC curve were FRS 30 L
      (H and CVD). When the cut-off values for these CVD risk scores were adjusted, the
      FRS 30 L H increased the negative predictive value for the low risk group from
      87.7 to 97.0% and the FRS 30 L CVD increased the positive predictive values for
      the high risk group from 69.7 to 85.7%. The CVD risk stratification of non
      elderly adults using FRS 30 L H and FRS 30 L CVD may be a useful tool for
      selecting candidate patients for diagnostic imaging studies that assess their SA
      prevalence.

PMID- 28493106
TI  - Human classifier: Observers can deduce task solely from eye movements.
AB  - Computer classifiers have been successful at classifying various tasks using eye
      movement statistics. However, the question of human classification of task from
      eye movements has rarely been studied. Across two experiments, we examined
      whether humans could classify task based solely on the eye movements of other
      individuals. In Experiment 1, human classifiers were shown one of three sets of
      eye movements: Fixations, which were displayed as blue circles, with larger
      circles meaning longer fixation durations; Scanpaths, which were displayed as
      yellow arrows; and Videos, in which a neon green dot moved around the screen.
      There was an additional Scene manipulation in which eye movement properties were
      displayed either on the original scene where the task (Search, Memory, or Rating)
      was performed or on a black background in which no scene information was
      available. Experiment 2 used similar methods but only displayed Fixations and
      Videos with the same Scene manipulation. The results of both experiments showed
      successful classification of Search. Interestingly, Search was best classified in
      the absence of the original scene, particularly in the Fixation condition. Memory
      also was classified above chance with the strongest classification occurring with
      Videos in the presence of the scene. Additional analyses on the pattern of
      correct responses in these two conditions demonstrated which eye movement
      properties successful classifiers were using. These findings demonstrate
      conditions under which humans can extract information from eye movement
      characteristics in addition to providing insight into the relative
      success/failure of previous computer classifiers.

PMID- 28493107
TI  - Beyond immunomodulation: The regenerative role for regulatory T cells in central
      nervous system remyelination.
AB  - Central nervous system regeneration after injury can occur in the form of
      remyelination, the reinstatement of myelin around axons which restores axon
      health and function. However, remyelination often fails in chronic neurological
      diseases, such as progressive multiple sclerosis. The lack of currently approved
      pro-remyelination therapies highlights the need to elucidate the cellular and
      molecular mechanisms underpinning this regenerative process. Whereas some T
      lymphocyte subsets such as Th1 and Th17 are implicated in inducing myelin injury,
      a recent study by Dombrowski et al. reveals a novel role for regulatory T cells
      (Tregs) in directly driving remyelination, independent of immunomodulation (Nat
      Neurosci doi: 10.1038/nn.4528 2017)(Dombrowski et al., 2017). This study is
      summarized in this Bits and Bytes.

PMID- 28493108
TI  - Percutaneous Septectomy in Chronic Dissection with Abdominal Aortic Aneurysm
      Creates Uniluminal Neck for EVAR.
AB  - PURPOSE: The intent of this report is to describe the technical details and
      rationale of endovascular septectomy using a wire saw maneuver in cases of
      chronic aortic dissection and associated infra-renal aortic aneurysm to allow
      standard endovascular abdominal aortic graft placement; preliminary clinical
      experience is also retrospectively reviewed. MATERIALS AND METHODS: Between June
      2013 and June 2016, four consecutive patients (mean age 55.3 years; range 52-58
      years) with chronic type B aortic dissection and isolated infra-renal abdominal
      aortic aneurysm (AAA) underwent endovascular aneurysm repair (EVAR) following
      guidewire septectomy to create a suitable proximal aortic landing zone. Technical
      success was evaluated by angiography performed at the end of the procedure.
      Procedural safety was determined by assessing any major adverse events through 30
      days of follow-up. Endoleaks and longer-term efficacy were evaluated. RESULTS:
      Four patients with chronic aortic dissections had associated AAA with a mean
      maximum diameter of 60 +/- 13 mm (range 50-77 mm). All underwent guidewire saw
      septectomy to facilitate EVAR. Following successful septectomy, standard
      abdominal bifurcated endografts were implanted uneventfully. No major adverse
      events and no endoleaks were noted on CT angiographic examinations through 30
      days following the procedure. Also, no rupture, re-intervention or endoleak has
      been noted during follow-up at a mean of 21.8 +/- 15 months (range 4-39 months).
      CONCLUSIONS: Guidewire saw septectomy is a technique that has the potential to
      create an anatomically suitable proximal neck for successful EVAR management of
      AAA in select patients with associated chronic aortic dissection.

PMID- 28493109
TI  - Effectiveness of the Conservative Therapy for Symptomatic Isolated Celiac Artery
      Dissection.
AB  - OBJECTIVE: To investigate the effectiveness of the conservative therapy for
      symptomatic isolated celiac artery dissection (ICAD). METHODS: Patients with
      symptomatic ICAD diagnosed on CT between February 2006 and June 2016 at three
      institutions were included. RESULTS: During the study period, a total of 24
      patients (22 men, 2 women) were included in this retrospective study. Patients
      most commonly presented with epigastric pain (n = 21) or back pain (n = 3).
      Initial CT findings included celiac arterial calcification (n = 3); compression
      of the true lumen (n = 24), including stenosis of the true lumen <50% (n = 14) or
      >=50% (n = 10); completely thrombosed (n = 11) or partially thrombosed (n = 5)
      false lumen; no thrombosis of the false lumen but presence of dissecting aneurysm
      (n = 8); and dissection extending to the common hepatic (n = 1) or splenic (n =
      6) artery. Twenty-three patients recovered after conservative treatment, and one
      patient who failed conservative treatment recovered after surgical therapy. Of
      the 23 patients who received conservative treatment, complete or partial
      remodeling of ICAD was achieved in 18 (78.3%) and 5 (21.7%) patients during 22.1
      +/- 13.3 months of follow-up. CONCLUSIONS: Conservative treatment can be applied
      successfully in most patients with symptomatic ICAD. Most cases of symptomatic
      ICAD resolve spontaneously within 2 years.

PMID- 28493110
TI  - BEM-based simulation of lung respiratory deformation for CT-guided biopsy.
AB  - PURPOSE: Accurate and real-time prediction of the lung and lung tumor deformation
      during respiration are important considerations when performing a peripheral
      biopsy procedure. However, most existing work focused on offline whole lung
      simulation using 4D image data, which is not applicable in real-time image-guided
      biopsy with limited image resources. In this paper, we propose a patient-specific
      biomechanical model based on the boundary element method (BEM) computed from CT
      images to estimate the respiration motion of local target lesion region, vessel
      tree and lung surface for the real-time biopsy guidance. METHODS: This approach
      applies pre-computation of various BEM parameters to facilitate the requirement
      for real-time lung motion simulation. The resulting boundary condition at end
      inspiratory phase is obtained using a nonparametric discrete registration with
      convex optimization, and the simulation of the internal tissue is achieved by
      applying a tetrahedron-based interpolation method depend on expert-determined
      feature points on the vessel tree model. A reference needle is tracked to update
      the simulated lung motion during biopsy guidance. RESULTS: We evaluate the model
      by applying it for respiratory motion estimations of ten patients. The average
      symmetric surface distance (ASSD) and the mean target registration error (TRE)
      are employed to evaluate the proposed model. Results reveal that it is possible
      to predict the lung motion with ASSD of [Formula: see text] mm and a mean TRE of
      [Formula: see text] mm at largest over the entire respiratory cycle. In the CT
      /electromagnetic-guided biopsy experiment, the whole process was assisted by our
      BEM model and final puncture errors in two studies were 3.1 and 2.0 mm,
      respectively. CONCLUSION: The experiment results reveal that both the accuracy of
      simulation and real-time performance meet the demands of clinical biopsy
      guidance.

PMID- 28493111
TI  - Parasympathetic Regulation and Inhibitory Control Predict the Development of
      Externalizing Problems in Early Childhood.
AB  - The current report examined the longitudinal relations between cognitive self
      regulation, physiological self-regulation, and externalizing problems. At age 4
      (n = 98; 49 girls) and 6 (n = 87; 42 girls), children completed the Day-Night
      task, which taps the inhibitory control dimension of executive function. During
      the task, cardiac activity was measured and respiratory sinus arrhythmia (RSA)
      was derived as an index of parasympathetic activity. Mothers reported on
      externalizing problems. A cross-lagged path model was used to estimate
      longitudinal predictions while controlling for stability in all constructs over
      time. Earlier inhibitory control negatively predicted later externalizing
      problems, but not vice versa. However, RSA reactivity moderated this link; better
      inhibitory control predicted fewer externalizing problems only when reactivity to
      the Day-Night task ranged from mild RSA suppression to RSA augmentation.
      Externalizing problems at 6 years were highest among preschoolers who augmented
      RSA but showed poor inhibitory control performance, suggesting that risk for
      psychopathology may be better delineated by viewing self-regulation from an
      integrated, multi-system perspective.

PMID- 28493112
TI  - The teaching of management of the pulp in primary molars across Europe.
AB  - AIM: To determine which methods of primary pulp therapy are currently being
      taught in European dental schools. METHODS: An online survey tool was employed to
      send questionnaires to paediatric dentistry departments of 202 European dental
      schools. Email addresses were obtained from the European Academy of Paediatric
      Dentistry and questionnaires were sent to one member of each department in
      December 2014. The survey included questions on treatment choices and clinical
      scenarios where respondents indicated how they would advise students to proceed,
      given a particular case. RESULTS: Fifty-one responses from 22 different countries
      were obtained. Eleven schools reported that they taught only undergraduate
      students, 4 only postgraduates and 36 taught both. Forty-three schools taught
      indirect pulp capping, the most popular material being calcium hydroxide; 26
      taught direct pulp capping, mostly using mineral trioxide aggregate (MTA).
      Teaching of pulpotomy was widespread across Europe, with MTA being the most
      popular material, taught in 37 schools, followed by ferric sulphate, in 29.
      Formocresol, however, was still being taught in 12 dental schools. Responses to
      the clinical scenarios were mostly in accordance with previously selected
      choices. CONCLUSIONS: This study had a representative sample, showing a wide
      variation in primary pulp therapies taught in Europe. Comparison with previous
      studies shows new trends in taught therapies, possibly driven by recent research
      in primary pulp management and the development of new materials.

PMID- 28493113
TI  - [Results of scrotal orchidopexie without ligation of an open processus].

PMID- 28493114
TI  - [Management of multiresistant bacteria in urology].
AB  - Contamination and infection with extensive drug resistant (XDR) bacteria are
      increasing in urology with the exception of methicillin resistant Staphylococcus
      aureus (MRSA) (stabilization). They often lead to logistic and therapeutical
      problems. Only 30-50% of XDR cases are of exogenous origin. To slow this trend,
      screening, hygiene programs, isolation, decontamination, targeted therapy of
      symptomatic infections, education programs, and success controls should be
      applied. Furthermore, all regulatory and legal instructions should be followed.
      Local hygiene networks help to find apt measures for XDR control. It is important
      to balance hygiene measures against hygiene hysteria. To prepare urological
      instruments, a local instrument preparation plan that takes into consideration
      all legal instructions should be followed. The efforts in health system general
      prophylactic measures should be supported. Only with consistent implementation in
      all areas of daily life (health care, local environment, animal husbandry, and
      soil contaminated within the framework of animal husbandry) can a substantial
      reduction of XDR bacteria be achieved in the long term.

PMID- 28493115
TI  - Cardiovascular Disease & Cancer Risk Among South Asians: Impact of Sociocultural
      Influences on Lifestyle and Behavior.
AB  - A comprehensive literature review revealed cultural beliefs, societal
      obligations, and gender roles within the South Asian community to be indirect
      contributors to the health of South Asian immigrants (SAIs). Health professionals
      need to increase their work with SAI communities to change less beneficial
      cultural elements such as misconceptions about health and exercise, and lack of
      communication when using alternative medicines. Community engaged efforts and
      continuing medical education are both needed to improve the health of the South
      Asian immigrant population in a culturally appropriate manner.

PMID- 28493116
TI  - General and Ethnic-Biased Bullying Among Latino Students: Exploring Risks of
      Depression, Suicidal Ideation, and Substance Use.
AB  - Using a cross-sectional sample of 534 Latino students from middle and high
      schools in a large North Carolina school district, we examined the relation of
      general and ethnic-biased bullying to depression and the indirect pathways
      through depression to suicidal ideation and substance use outcomes. A structural
      equation model tested the direct and indirect paths. The final model fit was
      excellent, chi2(90) = 127.6, p = .0056, RMSEA = 0.028, CFI = 0.974, TLI = 0.961.
      Ethnic-biased and verbal or relational bullying had a direct effect on
      depression, but general and physical bullying did not. Indirect effects through
      depression were found for ethnic-biased and verbal or relational bullying in
      relation to suicidal ideation, alcohol, and illicit drug use. Child nativity was
      marginally associated with ethnic-biased bullying, indicating foreign-born
      students may experience greater ethnic-biased bullying. Implications for future
      research and bullying prevention are discussed.

PMID- 28493117
TI  - Erratum to: Polar localization of MreB actin is inhibited by anionic
      phospholipids in the rod-shaped bacterium Escherichia coli.

PMID- 28493120
TI  - Strategies and Considerations for Improving Expression of "Difficult to Express"
      Proteins in CHO Cells.
AB  - Despite substantial advances in the field of mammalian expression, there are
      still proteins that are characterized as difficult to express. Determining the
      expression bottleneck requires troubleshooting techniques specific for the given
      molecule and host. The complex array of intracellular processes involved in
      protein expression includes transcription, protein folding, post-translation
      processing, and secretion. Challenges in any of these steps could result in low
      protein expression, while the inherent properties of the molecule itself may
      limit its production via mechanisms such as cytotoxicity or inherent instability.
      Strategies to identify the rate-limiting step and subsequently improve expression
      and production are discussed here.

PMID- 28493119
TI  - CO2 sensing in fungi: at the heart of metabolic signaling.
AB  - Adaptation to the changing environmental CO2 levels is essential for all living
      cells. In particular, microorganisms colonizing and infecting the human body are
      exposed to highly variable concentrations, ranging from atmospheric 0.04 to 5%
      and more in blood and specific host niches. Carbonic anhydrases are highly
      conserved metalloenzymes that enable fixation of CO2 by its conversion into
      bicarbonate. This process is not only crucial to ensure the supply of adequate
      carbon amounts for cellular metabolism, but also contributes to several signaling
      processes in fungi, including morphology and communication. The fungal specific
      carbonic anhydrase gene NCE103 is transcribed in response to CO2 availability. As
      recently shown, this regulation relies on the ATF/CREB transcription factor Cst6
      and the AGC family protein kinase Sch9. Here, we review the regulatory mechanisms
      which control NCE103 expression in the model organism Saccharomyces cerevisiae
      and the pathogenic yeasts Candida albicans and Candida glabrata and discuss which
      additional factors might contribute in this novel CO2 sensing cascade.

PMID- 28493121
TI  - Glycoengineering of CHO Cells to Improve Product Quality.
AB  - Chinese hamster ovary (CHO) cells represent the predominant platform in
      biopharmaceutical industry for the production of recombinant biotherapeutic
      proteins, especially glycoproteins. These glycoproteins include oligosaccharide
      or glycan attachments that represent one of the principal components dictating
      product quality. Especially important are the N-glycan attachments present on
      many recombinant glycoproteins of commercial interest. Furthermore, altering the
      glycan composition can be used to modulate the production quality of a
      recombinant biotherapeutic from CHO and other mammalian hosts. This review first
      describes the glycosylation network in mammalian cells and compares the
      glycosylation patterns between CHO and human cells. Next genetic strategies used
      in CHO cells to modulate the sialylation patterns through overexpression of
      sialyltransfereases and other glycosyltransferases are summarized. In addition,
      other approaches to alter sialylation including manipulation of sialic acid
      biosynthetic pathways and inhibition of sialidases are described. Finally, this
      review also covers other strategies such as the glycosylation site insertion and
      manipulation of glycan heterogeneity to produce desired glycoforms for diverse
      biotechnology applications.

PMID- 28493118
TI  - Position matters: multiple functions of LINC-dependent chromosome positioning
      during meiosis.
AB  - Chromosome positioning is crucial for multiple chromosomal events, including DNA
      replication, repair, and recombination. The linker of nucleoskeleton and
      cytoskeleton (LINC) complexes, which consist of conserved nuclear membrane
      proteins, were shown to control chromosome positioning and facilitate various
      biological processes by interacting with the cytoskeleton. However, the precise
      functions and regulation of LINC-dependent chromosome positioning are not fully
      understood. During meiosis, the LINC complexes induce clustering of telomeres,
      forming the bouquet chromosome arrangement, which promotes homologous chromosome
      pairing. In fission yeast, the bouquet forms through LINC-dependent clustering of
      telomeres at the spindle pole body (SPB, the centrosome equivalent in fungi) and
      detachment of centromeres from the SPB-localized LINC. It was recently found
      that, in fission yeast, the bouquet contributes to formation of the spindle and
      meiotic centromeres, in addition to homologous chromosome pairing, and that
      centromere detachment is linked to telomere clustering, which is crucial for
      proper spindle formation. Here, we summarize these findings and show that the
      bouquet chromosome arrangement also contributes to nuclear fusion during
      karyogamy. The available evidence suggests that these functions are universal
      among eukaryotes. The findings demonstrate that LINC-dependent chromosome
      positioning performs multiple functions and controls non-chromosomal as well as
      chromosomal events, and that the chromosome positioning is stringently regulated
      for its functions. Thus, chromosome positioning plays a much broader role and is
      more strictly regulated than previously thought.

PMID- 28493122
TI  - Large-Scale Transient Transfection of Chinese Hamster Ovary Cells in Suspension.
AB  - We describe a one-liter transfection of suspension-adapted Chinese hamster ovary
      (CHO-DG44) cells using polyethyleneimine (PEI) for DNA delivery. The method
      involves transfection at a high cell density (5 * 106 cells/mL) by direct
      addition of plasmid DNA (pDNA) and PEI to the culture and subsequent incubation
      at 31  degrees C with agitation by orbital shaking. We also describe an
      alternative method in which 90% of the pDNA is replaced by nonspecific (filler)
      DNA, and the production phase is performed at 31  degrees C in the presence of
      0.25% N, N-dimethylacetamide (DMA).

PMID- 28493123
TI  - Cloning of Single-Chain Antibody Variants by Overlap-Extension PCR for Evaluation
      of Antibody Expression in Transient Gene Expression.
AB  - Single-chain fragment variable-fragment crystallizable antibody constructs (scFv
      Fc) are homodimeric proteins representing valuable alternatives to
      heterotetrameric full-length IgG molecules to study protein properties and
      product-dependent cellular behavior. In contrast to naturally occurring
      antibodies, these artificial molecules are assembled from functional antibody
      domains to reduce molecule complexity and enhance antibody expression levels. The
      scFv-Fc format retains critical antibody functions such as antigen binding
      affinity and antibody effector functions. Here, we present a protocol to convert
      the full-length anti-HIV-1 IgG1 antibody 2F5 into a scFv-Fc construct. Variable
      and constant regions are amplified by conventional PCR reactions and assembled by
      a single overlap-extension PCR reaction. The amplified product is then cloned
      into a mammalian expression vector suitable for high-titer transient gene
      expression. This workflow can be applied to any antibody sequence by adapting the
      specific primer sequences to the antibody of choice.

PMID- 28493124
TI  - Anti-Apoptosis Engineering for Improved Protein Production from CHO Cells.
AB  - Improving the time integral of viable cell concentration by overcoming cell
      death, namely apoptosis, is one of the widely used strategies for efficient
      production of therapeutic proteins. By establishing stable cell lines that
      overexpress anti-apoptotic genes or down-regulate pro-apoptotic genes, the final
      product yields can be enhanced as cells become more resistance to environmental
      stresses. From the selection of high-expressing clones to verification of anti
      apoptotic activity, the method to construct a stable anti-apoptotic cell line is
      discussed in this chapter.

PMID- 28493125
TI  - Conditional Knockdown of Endogenous MicroRNAs in CHO Cells Using TET-ON-SanDI
      Sponge Vectors.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs of about 22 nucleotides in length
      and have proven to be useful targets for genetic modifications for desirable
      phenotype in the biotech industry. The use of constitutively expressed "miRNA
      sponge" vectors in which multiple, tandem miRNA binding sites containing
      transcripts are transcriptionally regulated by a constitutive promoter for down
      regulating the levels of endogenous microRNAs in Chinese hamster ovary (CHO)
      cells has shown to be more advantageous than using synthetic antisense
      oligonucleotides. The application of miRNA sponges in biotechnological processes,
      however, could be more effective, if expression of miRNA sponges could be tuned.
      In this chapter, we present a method for the generation of stable CHO cell lines
      expressing a TET-ON-SanDI-miRNA-sponge that is in theory expressed only in the
      presence of an inducer.

PMID- 28493126
TI  - Application of CRISPR/Cas9 Genome Editing to Improve Recombinant Protein
      Production in CHO Cells.
AB  - Genome editing has become an increasingly important aspect of Chinese Hamster
      Ovary (CHO ) cell line engineering for improving production of recombinant
      protein therapeutics. Currently, the focus is directed toward expanding the
      product diversity, controlling and improving product quality and yields. In this
      chapter, we present our protocol on how to use the genome editing tool Clustered
      Regularly Interspaced Short Palindromic Repeat (CRISPR)/CRISPR-associated protein
      9 (Cas9) to knockout engineering target genes in CHO cells. As an example, we
      refer to the glutamine synthetase (GS)-encoding gene as the knockout target gene,
      a knockout that increases the selection efficiency of the GS-mediated gene
      amplification system.

PMID- 28493127
TI  - Improved CHO Cell Line Stability and Recombinant Protein Expression During Long
      Term Culture.
AB  - Therapeutic proteins require proper folding and posttranslational modifications
      to be effective and biologically active. Chinese hamster ovary (CHO) cells are by
      far the most frequently used host for commercial production of therapeutic
      proteins. However, an unpredictable decrease in protein productivity during the
      time required for scale up impairs process yields, time, finance, and regulatory
      approval for the desired product. Therefore, it is important to assess cell lines
      at stages throughout the period of long-term culture in terms of productivity and
      various molecular parameters including plasmid and mRNA copy numbers and location
      of the plasmid on the host cell chromosome. Here, we describe methods, which are
      frequently used to analyze stability of the recombinant CHO cells over long-term
      culture. These procedures include the following; western blotting, ELISA to
      evaluate protein production, real-time PCR to analyze plasmid and mRNA copy
      numbers, and fluorescent in situ hybridization (FISH) to assess the location of
      the inserted plasmid on host cell chromosomes.

PMID- 28493128
TI  - Selection of High-Producing Clones Using FACS for CHO Cell Line Development.
AB  - Cell line development aims to generate and select clones with desirable
      characteristics. One of the most important parameters for biopharmaceutical cell
      selection is cell-specific productivity (Qp) or the quantity of product produced
      per cell per day. Fluorescence-activated cell sorting (FACS) is a powerful, high
      throughput technique that facilitates multiparametric characterization and
      isolation of individual cell clones from heterogeneous populations. Here, we
      describe a FACS-based method for section of high-producing CHO cell clones.

PMID- 28493129
TI  - The 'Omics Revolution in CHO Biology: Roadmap to Improved CHO Productivity.
AB  - Increased understanding of Chinese hamster ovary (CHO) cell physiology has been
      ushered in upon availability of the parental CHO-K1 cell line genome. Free and
      openly accessible sequence information has complemented transcriptomic and
      proteomic studies. The previous decade has also seen an increase in sensitivity
      and accuracy of proteomic methods due to technology development. In this genomic
      era, high-throughput screening methods, sophisticated informatic tools, and
      models continually drive major innovations in cell line development and process
      engineering. This review describes the various achievements in 'omics techniques
      and their application to improve recombinant protein expression from CHO cell
      lines.

PMID- 28493130
TI  - A Bioinformatics Pipeline for the Identification of CHO Cell Differential Gene
      Expression from RNA-Seq Data.
AB  - In recent years, the publication of genome sequences for the Chinese hamster and
      Chinese hamster ovary (CHO) cell lines has facilitated study of these
      biopharmaceutical cell factories with unprecedented resolution. Our understanding
      of the CHO cell transcriptome, in particular, has rapidly advanced through the
      application of next-generation sequencing (NGS) technology to characterize RNA
      expression (RNA-Seq). In this chapter, we present a computational pipeline for
      the analysis of CHO cell RNA-Seq data from the Illumina platform to identify
      differentially expressed genes. The example data and bioinformatics workflow
      required to run this analysis are freely available at
      www.cgcdb.org/rnaseq_analysis_protocol.html .

PMID- 28493131
TI  - Filter-Aided Sample Preparation (FASP) for Improved Proteome Analysis of
      Recombinant Chinese Hamster Ovary Cells.
AB  - Chinese hamster ovary (CHO) cells are the most commonly used mammalian host cell
      line for biopharmaceutical production because of their ability to correctly fold
      and posttranslationally modify recombinant proteins that are compatible with
      human use. Proteomics, along with other 'omic platforms, are being used to
      understand the biology of CHO cells with the ultimate aim of enhancing CHO cell
      factories for more efficient production of biopharmaceuticals. In this chapter,
      we will describe an efficient protocol called Filter Aided Sample Preparation
      (FASP) for the extraction of proteins from CHO cells for proteomic studies. FASP
      uses a common ultrafiltration device whereby the membrane pores are small enough
      to allow contaminating detergents to pass through, while proteins are too large
      and are retained and concentrated in the filter unit. This method of sample
      preparation and protein digestion is universally applicable and can be easily
      employed in any proteomics facilities as standard everyday laboratory reagents
      and equipment are used.

PMID- 28493132
TI  - Phosphopeptide Enrichment and LC-MS/MS Analysis to Study the Phosphoproteome of
      Recombinant Chinese Hamster Ovary Cells.
AB  - The reversible phosphorylation of proteins on serine, threonine, and tyrosine
      residues is one of the most important post-translational modifications that
      regulates many biological processes. The phosphoproteome has not been studied in
      any great detail in recombinant Chinese hamster ovary (CHO) cells to date despite
      phosphorylation playing a crucial role in regulating many molecular and cellular
      processes relevant to bioprocess phenotypes including, for example,
      transcription, translation, growth, apoptosis, and signal transduction. In this
      chapter, we provide a protocol for the phosphoproteomic analysis of Chinese
      hamster ovary cells using phosphopeptide enrichment with metal oxide affinity
      chromatography (MOAC) and immobilized metal affinity chromatography (IMAC)
      techniques, followed by site-specific identification of phosphorylated residues
      using LC-MS (MS2 and MS3) strategies.

PMID- 28493133
TI  - Engineer Medium and Feed for Modulating N-Glycosylation of Recombinant Protein
      Production in CHO Cell Culture.
AB  - Chinese hamster ovary (CHO) cells have become the primary expression system for
      the production of complex recombinant proteins due to their long-term success in
      industrial scale production and generating appropriate protein N-glycans similar
      to that of humans. Control and optimization of protein N-glycosylation is
      crucial, as the structure of N-glycans can largely influence both biological and
      physicochemical properties of recombinant proteins. Protein N-glycosylation in
      CHO cell culture can be controlled and tuned by engineering medium, feed, culture
      process, as well as genetic elements of the cell. In this chapter, we will focus
      on how to carry out experiments for N-glycosylation modulation through medium and
      feed optimization. The workflow and typical methods involved in the experiment
      process will be presented.

PMID- 28493134
TI  - Glycosylation Analysis of Therapeutic Glycoproteins Produced in CHO Cells.
AB  - In the last decades, the number of approved therapeutic proteins drugs is
      increasing exponentially and a large number of new therapeutic entities are
      progressing through clinical trials, solidifying biologics as the most promising
      class of pharmaceuticals on the market. Several cell lines are available for
      biopharmaceutical processes but mammalian cells are preferred since they give
      fewer problems for immunogenicity as they produce human-like post-translational
      modifications (PTMs). Glycosylation is the most common and complex (for both
      bioprocess engineering and quality control) of these modifications. Obtaining the
      desired glycosylation pattern is crucial for therapeutic proteins as it can
      impact significantly stability, half-life and safety as well as driving molecular
      processes, modifying the way drug interacts with patients' cells. As a
      consequence, glycosylation (like other PTMs) needs to be regulated and accurately
      analyzed during biopharmaceutical production. Herein we describe and discuss the
      analytical approaches for glycosylation analysis of therapeutic glycoproteins
      produced in CHO (Chinese Hamster Ovary) cells. This chapter will describe
      glycoprotein purification after separation from producing cell lines, N-glycan
      release and their variants fine structural characterization through mass
      spectrometry techniques.

PMID- 28493135
TI  - Characterization of Host Cell Proteins (HCPs) in CHO Cell Bioprocesses.
AB  - Host cell protein content during bioprocessing of biotherapeutic proteins
      generated from cultured Chinese hamster ovary (CHO) cells is typically measured
      using immunological and gel-based methods. Estimation of HCP concentration is
      usually undertaken using Enzyme-Linked ImmunoSorbent Assays (ELISA), while
      estimation of HCP clearance/presence can be achieved by comparing 2D-PAGE images
      of samples and by undertaking western blotting of 2D-PAGE analyzed samples. Here,
      we describe the analyses of HCP content using these methodologies.

PMID- 28493136
TI  - Risk factors for cardiovascular disease in subclinical hypothyroidism.
AB  - Subclinical hypothyroidism (SH), defined as an increased serum thyrotropin (TSH)
      level and normal plasma-free thyroid hormones' concentrations, is common in the
      general population, in particular, among elderly women. Its prevalence ranges
      from 4 to 15% and up to 20% among females aged > 60 year. Although SH has been
      associated with atherosclerotic cardiovascular disease (CVD), it is acknowledged
      that the high prevalence of dyslipidemia in elderly people is considered a common
      biochemical condition. Therefore, whether SH is associated with a higher risk for
      CVD is still controversial. At the moment, no consensus exists on the clinical
      significance and treatment of the mild form of thyroid failure, although
      available data suggest that only patients with plasma TSH levels above 10 mU/L
      may have an increased risk of CVD. However, treatment of SH in older individual
      requires special consideration with regard to thyroid hormone replacement therapy
      and expected clinical outcomes, since the increase of TSH observed in this
      population may represent a physiological process. It is likely that age affects
      TSH levels, and some studies suggest that modified reference limits for elderly
      populations should be considered in the diagnosis of mild thyroid failure.

PMID- 28493137
TI  - Effective dose rate coefficients for exposure to contaminated soil.
AB  - The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has
      undertaken calculations related to various environmental exposure scenarios. A
      previous paper reported the results for submersion in radioactive air and
      immersion in water using age-specific mathematical phantoms. This paper presents
      age-specific effective dose rate coefficients derived using stylized mathematical
      phantoms for exposure to contaminated soils. Dose rate coefficients for photon,
      electron, and positrons of discrete energies were calculated and folded with
      emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine
      equivalent and effective dose rate coefficients. The MCNP6 radiation transport
      code was used for organ dose rate calculations for photons and the contribution
      of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung
      and annihilation photons of positron emission were evaluated as discrete photons.
      The coefficients calculated in this work compare favorably to those reported in
      the US Federal Guidance Report 12 as well as by other authors who employed voxel
      phantoms for similar exposure scenarios.

PMID- 28493138
TI  - Effect of Light/Dark Regimens on Hydrogen Production by Tetraselmis
      subcordiformis Coupled with an Alkaline Fuel Cell System.
AB  - To improve the photoproduction of hydrogen (H2) by a green algae-based system,
      the effect of light/dark regimens on H2 photoproduction regulated by carbonyl
      cyanide m-chlorophenylhydrazone (CCCP) was investigated. A fuel cell was
      integrated into a photobioreactor to allow online monitoring of the H2 evolution
      rate and decrease potential H2 feedback inhibition by consuming the generated H2
      in situ. During the first 15 h of H2 evolution, the system was subjected to dark
      treatment after initial light illumination (L/D = 6/9 h, 9/6 h, and 12/3 h).
      After the dark period, all systems were again exposed to light illumination until
      H2 evolution stopped. Two peaks were observed in the H2 evolution rate under all
      three light/dark regimens. Additionally, a high H2 yield of 126 +/- 10 mL L-1 was
      achieved using a light/dark regimen of L 9 h/D 6 h/L until H2 production ceased,
      which was 1.6 times higher than that obtained under continuous illumination. H2
      production was accompanied by some physiological and morphological changes in the
      cells. The results indicated that light/dark regimens improved the duration and
      yield of H2 photoproduction by the CCCP-regulated process of Tetraselmis
      subcordiformis.

PMID- 28493139
TI  - [Lipedema: up-to-date of a long forgotten disease].
AB  - Lipedema is a chronic disorder of subcutaneous adipose tissue of unknown etiology
      not uncommon among post-puberty women. The disease has a negative impact on self
      esteem, mobility, and quality of life. Lipedema is characterized by symmetrical,
      disfiguring hyperplastic adipose tissue combined with bruising and pain.
      Untreated lipedema fosters osteoarthritis, secondary lymphedema, limited
      mobility, and psychosocial stigmatization. Treatment consists of conservative
      complex decongestive therapy and surgery by microcannular tumescent liposuction.
      Liposuction is the only available treatment capable to reduce the pathological
      adipose tissue durable and to prevent complications.

PMID- 28493140
TI  - [Health disorders and their prevalence in two primary care practices from the
      perspective of different coding].
AB  - Family practices provide medical care for the majority of health problems. This
      already highlights the importance of primary health care with respect to
      quantity. A detailed five-year survey of cases in two rural practices gives
      insight into everyday practice. During the whole period of this year's prevalence
      survey, 24,541 or 32,605 episodes of care were recorded in a mean practice
      population of 1500 or 1700 persons, respectively. The frequency rates of more
      than 500 different health problems show a typical Pareto distribution. This
      distribution of the cases characterizes the subject of general practice/family
      medicine and essentially determines handling illness in practice. Lack of a
      common technical language, with regard to the classification of health disorders,
      becomes evident when comparing the practices. An issue whose impact on medical
      care, education and research should be further investigated.

PMID- 28493141
TI  - Therapeutic strategies in adrenoleukodystrophy.
AB  - Adrenoleukodystrophy (ALD) is an X-linked hereditary disorder due to mutations of
      the ABCD1 gene, which encodes a peroxisomal transport protein necessary for very
      long-chain fatty acid degradation (VLCFA). Toxic accumulation thereof is
      associated with a proinflammatory state and eventual cell death in multiple
      tissues. ALD may manifest either as a fatal, rapidly progressive demyelinating
      disease in boys and adult men, or as a slowly progressive adult-onset long-tract
      myelopathy along with peripheral neuropathy. Our understanding of manifold
      mechanisms implicated in the disease pathology is currently incomplete, as
      neither genotype-phenotype correlation nor the trigger for cerebral disease has
      been described. Therapy objectives are therefore broadly aimed at correcting
      either the gene mutation or downstream molecular effects, such as oxidative
      stress. Advancements in disease detection, including the newly implemented
      newborn screening in the US and imaging modalities, allow for more timely
      intervention in the form of hematopoietic stem cell transplantation (HSCT), which
      may only be performed in early cerebral disease states.

PMID- 28493142
TI  - Sampling strategy and climatic implication of tree-ring cellulose oxygen isotopes
      of Hippophae tibetana and Abies georgei on the southeastern Tibetan Plateau.
AB  - The tree-ring cellulose oxygen isotopes (delta18O) for four trees of Hippophae
      tibetana and four trees of Abies georgei growing in different locations around
      the terminal moraine in Xincuo from 1951 to 2010 were measured to explore its
      potential for reconstructing climatic variations in the southeastern Tibetan
      Plateau. The mean and standard deviation of tree-ring delta18O at different
      heights do not have significant differences, and there are no significant
      differences in the mean and standard deviation of tree-ring delta18O between
      trees near the brook and trees at the top of moraine, indicating that we can
      collect samples for tree-ring delta18O analysis regardless of sampling heights
      and that the micro-environment does not affect tree-ring delta18O significantly.
      The mean inter-series correlations of cellulose delta18O for A. georgei/H.
      tibetana are 0.84/0.93, and the correlation between delta18O for A. georgei and
      H. tibetana is 0.92. The good coherence between inter-tree and inter-species
      cellulose delta18O demonstrates the possibility of using different species to
      develop a long chronology. Correlation analysis between tree-ring delta18O and
      climate parameters revealed that delta18O for A. georgei/H. tibetana had negative
      correlations (r = -0.62/r = -0.69) with relative humidity in July-August, and
      spatial correlation revealed that delta18O for A. georgei/H. tibetana reflected
      the regional Standardized Precipitation Evapotranspiration Index (29 degrees -32
      degrees  N, 88 degrees -98 degrees  E). In addition, tree-ring delta18O in Xincuo
      has a significant correlation with tree-ring delta18O in Bhutan. The results
      indicate that cellulose delta18O for A. georgei and H. tibetana in Xincuo is a
      good proxy for the regional hydroclimate.

PMID- 28493143
TI  - Differences in the importance of weather and weather-based decisions among
      campers in Ontario parks (Canada).
AB  - Parks and protected areas represent an important resource for tourism in Canada,
      in which camping is a common recreational activity. The important relationship
      between weather and climate with recreation and tourism has been widely
      acknowledged within the academic literature. Howbeit, the need for activity
      specific assessments has been identified as an on-going need for future research
      in the field of tourism climatology. Furthermore, very little is known about the
      interrelationships between personal characteristics and socio-demographics with
      weather preferences and behavioural thresholds. This study uses a stated climate
      preferences approach (survey responses) to explore differences in the importance
      of weather and related weather-based decisions among summer campers in Ontario
      parks. Statistically significant differences were found among campers for each of
      the four dependent variables tested in this study. Physically active campers
      placed greater importance on weather but were still more tolerant of adverse
      weather conditions. Older campers placed greater importance on weather. Campers
      travelling shorter distances placed greater importance on weather and were more
      likely to leave the park early due to adverse weather. Campers staying for longer
      periods of time were less likely to leave early due to weather and were willing
      to endure longer durations of adverse weather conditions. Beginner campers placed
      greater importance on weather, were more likely to leave early due to weather and
      recorded lower temporal weather thresholds. The results of this study contribute
      to the study of tourism climatology by furthering understanding of how personal
      characteristics such as gender, age, activity selection, trip duration, distance
      travelled, travel experience and life cycles affect weather preferences and
      decisions, focusing this time on recreational camping in a park tourism context.

PMID- 28493144
TI  - Differentiated seasonal vegetation cover dynamics of degraded grasslands in Inner
      Mongolia recorded by continuous photography technique.
AB  - Influence of climate change on the grassland phenology has attracted more and
      more attentions of ecologists. Although dozens of studies have been conducted,
      there have been few records examining the phenology differences of grasslands
      with different plant species compositions. Using continuous photography and image
      processing methods, this study examined seasonal vegetation cover dynamics of
      grasslands along a degradation gradient to clarify the influence of vegetation
      composition on the dynamics of vegetation cover during growing season. Our
      results revealed that phenological patterns of grasslands differentiated with
      their degradation status. Abandoned farmland (AF) and severely degraded grassland
      (SD) with most annuals and least climax species had the earliest start of growing
      season, while AF and extremely degraded grassland (ED) dominated by grasses had
      the earliest end of growing season. The start and end of growing season were
      strongly related to the relative cover of climax species and grasses. The results
      presented in this study support the possibility of using digital photography to
      capture the role of plant species composition on vegetation phenology in
      grasslands.

PMID- 28493145
TI  - Influence of the recipient body mass index on the outcomes after kidney
      transplantation.
AB  - PURPOSE: The relationship between the body mass index (BMI) of kidney transplant
      recipients and outcomes after kidney transplantation (KT) is not fully understood
      and remains controversial. We studied the influence of BMI on clinically relevant
      outcomes in kidney transplant recipients. METHODS: In this retrospective single
      centre study, all patients who underwent kidney transplantation at our
      institution between January 2007 and December 2012 were included. Demographic
      data and BMI were correlated with the clinical course of the disease, rejection
      rates, delayed graft function rates, and graft and patient survival. RESULTS:
      During the study period, 384 single KTs (130 women and 254 men) were performed.
      Seventeen percent of the transplants were transplanted within the Eurotransplant
      Senior Programme (ESP). Most of the transplants were performed using organs that
      were obtained from donors after brain death (DBD), and living donor kidney
      transplants were performed in 22.4% of all transplants. The median BMI of the
      recipients was 25.9 kg/m2. Additionally, 13.5% of the recipients had a BMI of 30
      34.9 kg/m2 and 3.9% had a BMI >35 kg/m2. A BMI >30 kg/m2 was significantly
      associated with primary non-function of the kidney (p = 0.047), delayed graft
      function (p = 0.008), and a higher rate of loss of graft function (p = 0.015).
      The glomerular filtration rate 12 months after KT was significantly lower in
      recipients with a BMI >30 kg/m2. Multivariate analysis revealed that recipient
      BMI, among other factors, was an independent risk factor for delayed graft
      function and graft survival. Patients with a BMI >30 kg/m2 had an almost four
      times higher risk for surgical site infection than did recipients with a lower
      BMI. CONCLUSIONS: Increased BMI at kidney transplantation is a predictor of
      adverse outcomes, including delayed graft function. These findings demonstrate
      the importance of the careful selection of patients and pre-transplant weight
      reduction, although the role of weight reduction for improving graft function is
      not clear.

PMID- 28493146
TI  - Laparoscopic proximal gastrectomy with oblique jejunogastrostomy.
AB  - BACKGROUND: Proximal early gastric cancer is a good indication for totally
      laparoscopic proximal gastrectomy (TLPG) with double-tract reconstruction (DTR).
      However, when most of the dietary intake passes through the escape route of the
      jejunum, the functional benefits of proximal gastrectomy might be similar to
      those after total gastrectomy. Our DTR procedure was improved for easy passage
      through the remnant stomach. The purposes of this study were to present a novel
      technique for intracorporeal DTR using linear staplers after TLPG and to
      investigate surgical outcomes. METHODS: DTR was performed using linear staplers
      only. A side-to-side jejunogastrostomy with twisting of both the remnant stomach
      and the anal jejunum was performed for the purpose of passing meals through the
      remnant stomach (an oblique jejunogastrostomy technique). The ten patients who
      underwent TLPG with DTR from January 2011 to August 2016 in Hokkaido University
      Hospital were retrospectively reviewed. Their clinicopathological characteristics
      and surgical and postoperative outcomes were collected and analyzed. RESULTS: The
      median duration of operation was 285 (range 146-440) min. No patients required
      blood transfusions. The number of dissected lymph nodes was 32 (range 22-56).
      There were no intraoperative complications, and no cases were converted to open
      surgery. All the patients were pT1N0M0 stage IA. No anastomotic leakage or
      complications were detected. Postoperative gastrography after reconstruction
      showed that contrast medium flowed mainly to the remnant stomach. The average
      percentage body weight loss was 14.0 +/- 7.1% at 10 months. The average
      percentage decrease in serum hemoglobin was 5.4 +/- 10.4% at 12 months.
      CONCLUSIONS: This novel technique for intracorporeal DTR provided a considerable
      advantage by the passage of dietary intake to the remnant stomach after LPG.

PMID- 28493147
TI  - Modified ALPPS procedures: more safety through less invasive surgery.
AB  - PURPOSE: Although associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) has been advocated for treating advanced liver tumors,
      increased morbidity and mortality remain serious problems. Many modified
      procedures have been devised to improve patient safety, but some confusion
      persists as to benefits and risks. METHODS: Modifications to ALPPS as originally
      reported were reviewed to clarify their contributions to safety and their
      clinical relevance. RESULTS: A variety of modifications are explained and
      considered. Modifications mainly aim to reduce adhesions, prevent tumor spread,
      avoid devascularization during liver splitting, and reduce surgical severity.
      Such changes aiming to increase safety and reduce invasiveness are needed to
      avoid high morbidity and mortality rates with this innovative procedure. However,
      these modified procedures still require more meaningful statistical comparisons
      of outcome. CONCLUSIONS: Prospective controlled studies are needed to confirm
      which modified procedures should be adopted in a standardized manner as an
      alternative to the original ALPPS. Further, we need to further explore mechanisms
      of liver regeneration, functional recovery, histopathologic changes of
      hepatocytes, and blood distribution during ALPPS simultaneously to developing and
      evaluating modifications of the procedure.

PMID- 28493149
TI  - Fitting growth curve models in the Bayesian framework.
AB  - Growth curve modeling is a popular methodological tool due to its flexibility in
      simultaneously analyzing both within-person effects (e.g., assessing change over
      time for one person) and between-person effects (e.g., comparing differences in
      the change trajectories across people). This paper is a practical exposure to
      fitting growth curve models in the hierarchical Bayesian framework. First the
      mathematical formulation of growth curve models is provided. Then we give step-by
      step guidelines on how to fit these models in the hierarchical Bayesian framework
      with corresponding computer scripts (JAGS and R). To illustrate the Bayesian GCM
      approach, we analyze a data set from a longitudinal study of marital relationship
      quality. We provide our computer code and example data set so that the reader can
      have hands-on experience fitting the growth curve model.

PMID- 28493148
TI  - Diversity of bacteria and archaea from two shallow marine hydrothermal vents from
      Vulcano Island.
AB  - To obtain new insights into community compositions of hyperthermophilic
      microorganisms, defined as having optimal growth temperatures of 80  degrees C
      and above, sediment and water samples were taken from two shallow marine
      hydrothermal vents (I and II) with temperatures of 100  degrees C at Vulcano
      Island, Italy. A combinatorial approach of denaturant gradient gel
      electrophoresis (DGGE) and metagenomic sequencing was used for microbial
      community analyses of the samples. In addition, enrichment cultures, growing
      anaerobically on selected polysaccharides such as starch and cellulose, were also
      analyzed by the combinatorial approach. Our results showed a high abundance of
      hyperthermophilic archaea, especially in sample II, and a comparable diverse
      archaeal community composition in both samples. In particular, the strains of the
      hyperthermophilic anaerobic genera Staphylothermus and Thermococcus, and strains
      of the aerobic hyperthermophilic genus Aeropyrum, were abundant. Regarding the
      bacterial community, epsilon-Proteobacteria, especially the genera Sulfurimonas
      and Sulfurovum, were highly abundant. The microbial diversity of the enrichment
      cultures changed significantly by showing a high dominance of archaea,
      particularly the genera Thermococcus and Palaeococcus, depending on the carbon
      source and the selected temperature.

PMID- 28493150
TI  - Assessing liver proteins and enzymes of medical workers exposed to ionizing
      radiation (IR).
AB  - The cross-sectional study was conducted to examine hepatic function via liver
      enzymes/proteins assessments, along with the estimation of an inflammatory
      response from C-reactive protein (CRP)-which is a liver-synthesized protein. The
      liver function tests with aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin (BBN), and CRP
      test were conducted for radiation-exposed workers-REW (n = 32) and radiation
      unexposed workers-RUW (n = 21). The annual average effective doses (AAED) were
      measured from thermoluminescent dosimeter. A t test and bivariate correlation
      analyses were applied. Only one worker had a high AST value (50 U/L), one worker
      had a negligible high ALT value (43 U/L) and only one worker had a negligible
      high bilirubin value (1.3 g/dL). There were normal levels of CRP (up to 6 mg/L)
      in all individuals. There existed a nonsignificant difference (p < 0.050) between
      the mean values of liver enzymes and proteins in all exposed and unexposed
      workers. Nonsignificant weak correlations are reported in liver enzymes/proteins
      parameters: AST, ALT, ALP, BBN, CRP with the AAED range (whole-body: 0.91-3.39
      mSv) during 2011-2015. The normal values of liver enzymes/proteins' (AST, ALT,
      ALP, BBN, CRP) values may ensure a good hepatic health of radiation-exposed
      medical workers with AAED range mentioned. We found that low ionizing radiation
      doses did not alter the liver function test parameters and did not affect the
      concentration of an inflammatory response protein, i.e., CRP.

PMID- 28493151
TI  - Avoidant coping moderates the relationship between stress and depressive
      emotional eating in adolescents.
AB  - BACKGROUND: Studies with adults support an association between emotional eating
      and avoidant and emotion-focused coping styles. While an avoidant coping style
      has been identified as a risk-factor for eating disorders in adolescents, no
      studies to date have specifically examined the relationship between coping styles
      and emotional eating in this population. The purpose of the present study was to
      assess whether coping styles moderate the relationship between perceived stress
      and emotional eating in adolescents. METHOD: Two hundred and seventy-seven middle
      school students (mean age = 13.26 years; SD = 0.49) completed the Emotional
      Eating Scale for Children and Adolescents, the Perceived Stress Scale, the
      Children's Coping Strategies Checklist, and a brief demographic survey. Four
      separate multiple linear regression analyses were conducted to determine the
      interactive effects of perceived stress and coping styles on emotional eating.
      RESULTS: The interaction between perceived stress and an avoidant coping style
      accounted for a significant amount of variance in the Emotional Eating Depression
      subscale score (EES-C-DEP); at higher levels of perceived stress, an avoidant
      coping style increased an adolescent's propensity for depressive emotional
      eating. CONCLUSIONS: The present findings provide preliminary support for
      targeting an avoidant coping style in preventative interventions, particularly
      for youth that have the propensity to overeat in response to feelings of
      depression.

PMID- 28493152
TI  - Inhibition of miR-274-3p increases BmCPV replication by regulating the expression
      of BmCPV NS5 gene in Bombyx mori.
AB  - Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is one of the major pathogens
      that pose a big challenge to the sericulture industry. Growing evidences have
      shown that microRNAs play key roles in the regulations of host-pathogen
      interactions in insects. MicroRNAs have been found in silkworms, whether and how
      they affect the silkworm-BmCPV interactions are still unknown. Here we
      investigate the effect of miR-274-3p on the BmCPV replication in the BmCPV
      infected silkworm larvae. In our study, BmCPV Nonstructural protein 5 (NS5) was
      identified to be the target of miR-274-3p based on bioinformatics analysis and
      luciferase reporter assay. The abundance of NS5 was significantly increased in
      the presence of miR-274-3p inhibitor based on the qRT-PCR and Western blotting
      results. Further, qRT-PCR results revealed that the expression of polyhedrin gene
      of BmCPV in the larvae after applying miR-274-3p inhibitor was significantly
      increased comparing with that of larvae with negative control. Our results
      suggest that inhibition of miR-274-3p could facilitate BmCPV replication by up
      regulating BmCPV NS5 gene expression and are insightful for further exploring the
      interactions between silkworm and BmCPV.

PMID- 28493153
TI  - A Bird's Eye View.

PMID- 28493154
TI  - [Transcutaneous osseointegration (part 2)].

PMID- 28493155
TI  - ?

PMID- 28493156
TI  - Mini-review: high rate algal ponds, flexible systems for sustainable wastewater
      treatment.
AB  - Over the last 20 years, there has been a growing requirement by governments
      around the world for organisations to adopt more sustainable practices.
      Wastewater treatment is no exception, with many currently used systems requiring
      large capital investment, land area and power consumption. High rate algal ponds
      offer a sustainable, efficient and lower cost option to the systems currently in
      use. They are shallow, mixed lagoon based systems, which aim to maximise
      wastewater treatment by creating optimal conditions for algal growth and oxygen
      production-the key processes which remove nitrogen and organic waste in HRAP
      systems. This design means they can treat wastewater to an acceptable quality
      within a fifth of time of other lagoon systems while using 50% less surface area.
      This smaller land requirement decreases both the construction costs and
      evaporative water losses, making larger volumes of treated water available for
      beneficial reuse. They are ideal for rural, peri-urban and remote communities as
      they require minimum power and little on-site management. This review will
      address the history of and current trends in high rate algal pond development and
      application; a comparison of their performance with other systems when treating
      various wastewaters; and discuss their potential for production of added-value
      products. Finally, the review will consider areas requiring further research.

PMID- 28493157
TI  - Determination of the biofilm production capacities and characteristics of members
      belonging to Bacillaceae family.
AB  - The biofilm characteristics of many endospore-forming bacilli, especially the
      thermophiles are still unclear. In this study, a detailed identification and
      description of biofilm production characteristics of totally 145 isolates and
      reference strains belonging to Bacillaceae family, displaying thermophilic (n =
      115), facultative thermophilic (n = 24) and mesophilic (n = 6) growth from genera
      Anoxybacillus, Geobacillus, Thermolongibacillus, Aeribacillus, Brevibacillus,
      Paenibacillus and Bacillus were presented. The incubation temperatures were
      adjusted to 37, 45 and 55-65  degrees C for mesophiles, facultative thermophiles,
      and thermophiles, respectively. The bacilli were evaluated based on their colony
      morphotypes on Congo red (CR) agar, their complex exopolysaccharide production on
      calcofluor supplemented tryptic soy agar, and as well as their pellicle formation
      at the liquid-air surface in tryptic soy broth cultures. Their biofilm production
      capabilities were also tested on abiotic surfaces of both polystyrene and
      stainless steel by crystal violet binding assay and viable biofilm cell
      enumerations, respectively. As a result, the biofilm production capacities of
      Bacillaceae members from genera to species level, the effects of osmolarity,
      temperature, incubation time and abiotic surfaces on biofilm formation as well as
      the CR morphotypes associated with the biofilm production were able to reveal in
      a wide group of bacilli. Besides, general enrichment-inoculation approaches and
      methodologies were also offered, which allow and facilitate the screening and
      determining the biofilm producing endospore forming bacilli.

PMID- 28493159
TI  - [Personalized intensive care in the age of standardization].

PMID- 28493160
TI  - ?

PMID- 28493158
TI  - Common Variable Immunodeficiency Caused by FANC Mutations.
AB  - Common variable immunodeficiency (CVID) is the most common adult-onset primary
      antibody deficiency disease due to various causative genes. Several genes, which
      are known to be the cause of different diseases, have recently been reported as
      the cause of CVID in patients by performing whole exome sequencing (WES)
      analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in
      two patients. B cells were absent and CD4+ T cells were skewed toward CD45RO+
      memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa
      deleting recombination excision circles (sjKRECs) were undetectable in both
      patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using
      WES, we identified compound heterozygous mutations of FANCE in one patient and
      homozygous mutation of FANCA in another patient. The impaired function of FANC
      protein complex was confirmed by a monoubiquitination assay and by chromosome
      fragility test. We then performed several immunological evaluations including
      quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals
      with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have
      immunological abnormalities, suggesting that such immunological findings may be
      common in FA patients. These data indicate that FANC mutations are involved in
      impaired lymphogenesis probably by the accumulation of DNA replication stress,
      leading to CVID. It is important to diagnose FA because it drastically changes
      clinical management. We propose that FANC mutations can cause isolated
      immunodeficiency in addition to bone marrow failure and malignancy.

PMID- 28493162
TI  - Single-setting endoscopic retrograde cholangiopancreatography (ERCP) and
      cholecystectomy improve the rate of surgical site infection.
AB  - INTRODUCTION: Cholecystectomy is a common surgical procedure. The presence of
      common bile duct stones complicates treatment, often requiring a second procedure
      for stone retrieval. For such patients, endoscopic retrograde
      cholangiopancreatography (ERCP) provides adequate therapy, and can be performed
      before, after, or at the same time as cholecystectomy. In 2013, duodenoscopes
      were implicated by the Centers for Disease Control and Prevention in transmission
      of carbapenem-resistant Enterobacteriaceae. In this study, we sought to determine
      if the addition of ERCP to cholecystectomy was associated with higher rates of
      surgical site infections and microbial resistance. HYPOTHESIS: Adding ERCP to
      cholecystectomy increases the SSI rate. METHODS: For this retrospective review,
      we used the SSI surveillance database at our tertiary-care academic hospital.
      Cholecystectomy cases between 2010 and 2015 were included in the analysis. SSI
      was diagnosed using criteria of CDC's National Healthcare Safety Network (NHSN).
      We applied a logistic regression model to our data (SAS Studio software, v3.4,
      Enterprise Edition). RESULTS: Our 6-year study period included 2201
      cholecystectomies. The SSI rate was 4.1 times higher for patients who underwent
      open cholecystectomy as compared with laparoscopic cholecystectomy (95% CI 1.61
      10.24). When adjusted for wound class and procedure type, the SSI rate was
      significantly higher for patients who underwent ERCP within 60 days before
      cholecystectomy (P = 0.04; OR 2.2; CI 1.04-4.49). Rates of resistant pathogens
      were significantly higher in patients who underwent ERCP in addition to
      cholecystectomy (1.1% vs. 0.2%, P = 0.02, Fisher's exact test). CONCLUSIONS: ERCP
      performed in the same setting as cholecystectomy carries no increased risk of SSI
      and should be the treatment of choice in patients with choledocholithiasis. ERCP
      performed separately within 60 days before cholecystectomy doubles the risk of
      SSI. Contaminated equipment might play a role, but other factors are likely at
      play, and should be taken into account when selecting treatment pathways for
      patients with choledocholithiasis.

PMID- 28493161
TI  - Primary versus redo paraesophageal hiatal hernia repair: a comparative analysis
      of operative and quality of life outcomes.
AB  - INTRODUCTION: We compared patient outcomes after initial versus redo
      paraesophageal hernia (PEH) repair at two high-volume GI surgery centers.
      MATERIALS AND METHODS: Retrospective review analyzed one-year outcomes after
      initial versus redo elective laparoscopic PEH repair, including wound/non-wound
      related complications and quality of life benefits as measured by four validated
      instruments: reflux symptom index, gastroesophageal reflux disease health
      related, laryngopharyngeal reflux, and swallowing scales. RESULTS: Three hundred
      and seventeen patients (271 initial and 46 redo) underwent laparoscopic PEH
      repair. Groups differed with respect to age (64.6 vs. 60.2 years, p = 0.027), but
      were comparable in gender (71.2 vs. 67.4% female, p = 0.596), BMI (29.0 vs. 27.6
      kg/m2, p = 0.100), and ASA score (2.3 vs. 2.3 p = 0.666). Redo surgery was more
      complex with longer mean operative times (112.2 vs. 139.1 min, p < 0.001). Groups
      did not statistically differ with respect to 30-day wound (0.7 vs. 2.2%, p =
      0.363) and non-wound (6.0 vs. 8.7%, p = 0.511)-related complications. After one
      year of follow-up, QOL analysis revealed that initial versus redo groups
      significantly benefited from operative intervention. CONCLUSIONS: Although redo
      PEH repairs are more complex, patients enjoy equivalent operative outcomes and
      quality of life benefits compared to initial surgery lending support to the
      significance of surgeon experience and high-volume centers in optimizing
      outcomes.

PMID- 28493163
TI  - A comparison between totally laparoscopic hydrocelectomy and scrotal incision
      hydrocelectomy with laparoscopic high ligation for pediatric cord hydrocele.
AB  - BACKGROUND: The purpose of this study is to report clinical characteristics and
      to investigate the feasibility and safety of totally laparoscopic hydrocelectomy
      (TLH) compared to scrotal incision hydrocelectomy with laparoscopic high ligation
      (SIH) for pediatric cord hydrocele (CH). METHODS: From September 2011 to February
      2016, 148 patients underwent SIH, and 342 patients underwent TLH for CH. In the
      TLH group, a large hydrocele that could not pass through the internal ring was
      removed after percutaneous syringe aspiration. Age, laterality of hydrocele,
      inguinal comorbidities, operation time, surgical complications, and recurrences
      were evaluated. RESULTS: All the patients had spermatic cord cysts and patent
      processus vaginalis in proximity to hydrocele (mixed type). The mean age of CH
      patients was 34.1 +/- 22.1 months. CHs are more common on the right side (61.0%)
      than on the left (35.7%). Bilaterality occurred in 3.3%. Comorbidities such as
      hernia (8.6%) and cryptorchidism (1.2%) were observed. There were no
      complications except for two cases of wound hematoma in SIH group. There was one
      (0.7%) case of recurrence appeared in communicating hydrocele in SIH group. There
      were no significant differences in the age, laterality of hydrocele, inguinal
      comorbidities, operation time, complications, and recurrences between TLH and SIH
      groups. However, TLH for unilateral cord hydrocele had significantly shorter
      operation time compared to SIH. The mean operation time in TLH group was 15.6 +/-
      5.96 min and there was no conversion to open surgery. CONCLUSIONS: TLH for
      pediatric CH is a feasible and safe procedure without additional incisions.
      Therefore, TLH can be one of the surgical options for pediatric CH especially in
      mixed type.

PMID- 28493164
TI  - The model for end-stage liver disease predicts outcomes in patients undergoing
      cholecystectomy.
AB  - BACKGROUND: The magnitude of risk for patients undergoing cholecystectomy with
      high model for end-stage liver disease (MELD) scores is poorly understood.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program database from 2005 to 2013 was used to study patients undergoing
      cholecystectomy. Patients were excluded if they had choledocholithiasis or
      preoperative dialysis. Bivariate data analysis was performed and logistic
      regression modeling was conducted to calculate risk-adjusted 30-day outcomes.
      RESULTS: A total of 63,464 patients were included in the study. Unadjusted
      mortality significantly increased as the MELD score increased in the laparoscopic
      (MELD = 6-10, 0.2%; 11-15, 1.1%; 16-20, 3.2%; >20, 5.8%) and open groups (MELD =
      6-10, 1.5%; 11-15, 3.7%; 16-20, 8.6%; >20, 17.9%) (p-value <0.001 for both).
      Unadjusted morbidity also increased with MELD score increases in the laparoscopic
      (MELD = 6-10, 3.8%; 11-15, 9.9%; 16-20, 16.3%; >20, 22.8%) and open groups (MELD
      = 6-10, 18.7%; 11-15, 28.2%; 16-20, 40.7%; >20, 57.8%) (p-value <0.001 for both).
      Patients with ascites and high MELD scores had higher rates of mortality
      (laparoscopic, MELD > 20, 33.3%; open, MELD > 20, 48.5%) and morbidity
      (laparoscopic, MELD > 20, 66.7%; open, MELD > 20, 75.8%) across all MELD scores.
      After adjustment, MELD score acted as a progressive and independent predictor of
      morbidity and mortality. CONCLUSIONS: The MELD score is an objective and easy to
      calculate scoring system that independently predicts postoperative morbidity and
      mortality in patients undergoing cholecystectomy. Patients with ascites have
      substantially worse outcomes across all MELD scores. Open cholecystectomy is
      associated with significantly more morbidity and mortality than laparoscopic
      cholecystectomy across all MELD groups.

PMID- 28493165
TI  - Minimally invasive distal pancreatectomy: greatest benefit for the frail.
AB  - OBJECTIVE: The benefits of minimally invasive distal pancreatectomy (MIDP) over
      open surgery continue to be investigated. Frailty is a known predictor of
      postoperative outcome. We hypothesized that the benefit of minimally invasive
      distal pancreatectomy is the greatest for the frailest of patients. METHODS: Data
      from the pancreas-targeted National Surgical Quality Improvement Program (NSQIP)
      database for 2014 were reviewed. A modified frailty index (mFI) with 11
      preoperative variables previously validated for use in NSQIP was used to
      determine the correlation between frailty and postoperative outcomes, including
      Clavien grade IV complications. Patients were classified into non-frail (mFI = 0)
      or frail (mIF > 0), in which they were subclassified into mildly frail (mFI 1 or
      2) or severely frail (mFI = 3). RESULTS: A total of 1,038 distal pancreatectomies
      (DP) were included in the analysis, of which 387 were minimally invasive (MIDP:
      laparoscopic: 285, robotic: 102), 558 open DP (ODP), and 93 MIDP converted to
      open (MIDPcODP: laparoscopic: 80, robotic: 13). More than 90% of patients had an
      mFI of 0 or 1 (mFI 0 = 473 (45.6%), 1 = 466 (44.9%), 2 = 94 (9.1%), and 3 = 5
      (0.5%), respectively). Overall, 4.6% of patients experienced Clavien grade IV
      complications and 1.1% a mortality. Non-frail patients experienced a similar rate
      of grade IV Clavien complications with MIDP vs. ODP vs. MIDPcOP (2.3 vs. 2.3 vs.
      4.9%; p = 0.6), whereas frail patients (mFI > 0) had a lower rate of
      complications with MIDP (2.4 vs. 8.3 vs. 11.5; p = 0.007). Worsening frailty
      correlated with an increase in complications (non-frail: 2.5%; mildly frail:
      6.3%; severely frail: 20%; p = 0.005). CONCLUSION: MIDP is associated with a
      lower risk of Clavien grade IV complications compared to ODP for frail patients,
      especially for benign disease. Thus, minimally invasive approach may mitigate
      risk in frail patients.

PMID- 28493166
TI  - Psychometric properties of the Fundamentals of Endoscopic Surgery (FES) skills
      examination.
AB  - BACKGROUND: The Fundamentals of Endoscopic Surgery (FES) manual skills
      examination is a simulation-based assessment of five foundational skills in
      endoscopic surgery. With the FES skills exam becoming part of the board
      certification process in general surgery, continual investigation is needed to
      determine the validity with which the exam is supporting inferences and decision
      making about examinees, as well as how it might be improved. METHODS: The present
      study retrospectively analyzed performance and demographic details for the
      initial 344 examinees completing the FES skills exam. RESULTS: The five tasks
      showed distinct degrees of difficulty, with Loop Reduction being especially
      difficult for examinees. Tasks related to one another positively but moderately,
      suggesting that the exam assesses both general and task-specific skills. The
      number of lower-endoscopic cases completed by an examinee strongly predicted
      performance, while upper endoscopy experience and career level (e.g., resident
      vs. fellow vs. practicing) did not. Hand dominance and the type of simulator used
      were not found to be related to scores. However, three demographic variables that
      related to one another-gender, glove size, and height-were also related to
      performance and pass/fail status. CONCLUSIONS: This study's results generally
      support the validity argument for the FES skills exam while pointing to
      additional investigations to be undertaken as the exam is applied more broadly.

PMID- 28493167
TI  - Diagnostic yield of small histological cores obtained with a new EUS-guided fine
      needle biopsy system.
AB  - BACKGROUND: As endoscopic ultrasound-guided tissue acquisition techniques evolve,
      there is increasing interest in obtaining optimal histological samples to improve
      diagnostic accuracy. In this study, we aimed to assess the tissue acquisition
      success rate and test performance characteristics of a novel endoscopic
      ultrasound-guided fine needle biopsy (EUS-FNB) system. METHODS: We performed a
      retrospective review of consecutive patients undergoing EUS-guided tissue
      sampling of solid lesions using the SharkCore fine needle system in a tertiary
      referral facility. At least two passes were submitted for histology and
      diagnostic accuracy was evaluated. Comparison standard was based on final
      surgical pathology or minimum six-month clinical follow-up. RESULTS: Seventy-nine
      patients underwent 85 EUS-FNB procedures. Of the 85 histology specimens, 78
      (91.7%) were adequate for diagnostic examination (includes six
      atypical/suspicious for adenocarcinoma). The sensitivity, specificity, and
      accuracy for diagnosis of malignancy with FNB were 87.1, 100, and 90.6%,
      respectively. Cytology was simultaneously sent in 43 cases with the same needle
      in addition to histology. Out of the 14 cases that were atypical/suspicious for
      adenocarcinoma or non-diagnostic on cytology, 11 cases (78.6%) achieved definite
      diagnoses on histology. The overall sensitivity, specificity, and accuracy for
      diagnosis of malignancy combining histology and cytology were 90.3, 100, and
      92.9%, respectively. No complications were reported after the procedures.
      CONCLUSION: In this initial experience with a new EUS-guided FNB system,
      obtaining small cores to submit for histological analysis was safe, technically
      feasible, and highly accurate. Most of the histological cores obtained via FNB
      yielded a definite diagnosis including in cases with equivocal cytomorphology.
      Further study is required to confirm these findings.

PMID- 28493168
TI  - Comparative statistical component analysis of transgenic, cyanophycin-producing
      potatoes in greenhouse and field trials.
AB  - Potatoes are a promising system for industrial production of the biopolymer
      cyanophycin as a second compound in addition to starch. To assess the efficiency
      in the field, we analysed the stability of the system, specifically its
      sensitivity to environmental factors. Field and greenhouse trials with transgenic
      potatoes (two independent events) were carried out for three years. The influence
      of environmental factors was measured and target compounds in the transgenic
      plants (cyanophycin, amino acids) were analysed for differences to control
      plants. Furthermore, non-target parameters (starch content, number, weight and
      size of tubers) were analysed for equivalence with control plants. The huge
      amount of data received was handled using modern statistical approaches to model
      the correlation between influencing environmental factors (year of cultivation,
      nitrogen fertilization, origin of plants, greenhouse or field cultivation) and
      key components (starch, amino acids, cyanophycin) and agronomic characteristics.
      General linear models were used for modelling, and standard effect sizes were
      applied to compare conventional and genetically modified plants. Altogether, the
      field trials prove that significant cyanophycin production is possible without
      reduction of starch content. Non-target compound composition seems to be
      equivalent under varying environmental conditions. Additionally, a quick test to
      measure cyanophycin content gives similar results compared to the extensive
      enzymatic test. This work facilitates the commercial cultivation of cyanophycin
      potatoes.

PMID- 28493170
TI  - Eluxadoline: A Review in Diarrhoea-Predominant Irritable Bowel Syndrome.
AB  - Eluxadoline (Truberzi(r)) is an orally administered, minimally absorbed agent
      that acts locally in the gastrointestinal tract as a mixed u-opioid receptor
      agonist and delta-opioid receptor antagonist. The randomized, double-blind,
      placebo-controlled, multinational, phase 3 IBS-3001 and IBS-3002 trials examined
      the efficacy of eluxadoline in patients with diarrhoea-predominant irritable
      bowel syndrome (IBS-D). The composite response rate (i.e. the proportion of
      patients with improvement in both worst abdominal pain and stool consistency on
      >=50% of days; primary endpoint), was significantly higher in patients receiving
      eluxadoline 100 mg twice daily than in those receiving placebo after 12 and 26
      weeks' therapy. Other abdominal and bowel symptoms (e.g. bloating, urgency,
      frequency of bowel movement) and health-related quality of life scores were also
      improved with eluxadoline. Eluxadoline was generally well tolerated in patients
      with IBS-D. Constipation was the most commonly occurring adverse event, although
      no serious constipation events were reported. Pancreatitis and adverse events
      consistent with sphincter of Oddi spasm were uncommon. In conclusion, eluxadoline
      is a new option to consider in the treatment of adult patients with IBS-D.

PMID- 28493169
TI  - Empathy for Distress in Humans and Rodents.
AB  - Empathy is traditionally thought to be a unique ability of humans to feel,
      understand, and share the emotional state of others. However, the notion has been
      greatly challenged by the emerging discoveries of empathy for pain or distress in
      rodents. Because empathy is believed to be fundamental to the formation of
      prosocial, altruistic, and even moral behaviors in social animals and humans,
      studies associated with decoding the neural circuits and unraveling the
      underlying molecular and neural mechanisms of empathy for pain or distress in
      rodents would be very important and encouraging. In this review, the author set
      out to outline and update the concept of empathy from the evolutionary point of
      view, and introduce up-to-date advances in the study of empathy and its neural
      correlates in both humans and rodents. Finally, the author highlights the
      perspectives and challenges for the further use of rodent models in the study of
      empathy for pain or distress.

PMID- 28493171
TI  - Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives.
AB  - Cytotoxic chemotherapy has been the only systemic treatment of locally advanced
      and metastatic urothelial carcinoma for decades. Long-term survival remains
      stagnant around 12-14 months for patients with advanced disease who have
      progressed on or recurred after receiving first-line platinum-based chemotherapy.
      Improving clinical outcomes for patients with urothelial carcinoma in all disease
      settings requires the development of novel treatments, especially for patients
      who failed on first-line chemotherapy. Since the discovery of intravesical
      Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease,
      there have not been any major breakthrough drugs that exploit the immune
      sensitivity of bladder cancer until recently. Immune-checkpoint inhibitors
      targeting the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and
      cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways have shown
      significant anti-tumor activity, tolerable safety profiles and durable, long-term
      responses in clinical trials. Atezolizumab, avelumab, durvalumab, nivolumab and
      pembrolizumab are promising PD-1/PD-L1 blockade drugs under investigation that
      will redefine the standard of care for bladder cancer. CTLA-4 inhibitors are also
      under investigation in this setting. Atezolizumab, approved in May 2016, and
      nivolumab, approved in February 2017, are the first Food and Drug Administration
      (FDA)-approved immune-checkpoint inhibitors in bladder cancer for platinum
      pretreated patients based on phase II data. On March 16, 2017, results from the
      phase III trial KEYNOTE-045 demonstrated that survival was significantly longer
      in patients treated with pembrolizumab when compared with the standard second
      line chemotherapy. Research into biomarkers such as PD-L1 expression, messenger
      RNA subtype, mutational and neoantigen load and gene signature expression will be
      crucial to determining why some patients respond to immunotherapy and others do
      not. This review article describes the advances in immunotherapy since the
      development of BCG, presents results from clinical trials investigating immune
      checkpoint inhibitors and discusses biomarkers and prognostic factors associated
      with response to these new drugs.

PMID- 28493172
TI  - Tenofovir Alafenamide: A Review in Chronic Hepatitis B.
AB  - Tenofovir alafenamide (AF) [Vemlidy(r)], an oral prodrug of tenofovir, was
      developed to optimize the antiviral potency and clinical safety of the active
      moiety tenofovir diphosphate (selective reverse transcriptase nucleotide
      inhibitor). In two identically designed, ongoing, multinational trials in
      treatment-naive and -experienced adult patients with hepatitis B e antigen
      (HBeAg)-positive or -negative chronic hepatitis B virus (HBV) infection, once
      daily tenofovir AF 25 mg provided effective and sustained viral suppression (120
      week analysis), and was generally well tolerated. In the primary 48-week
      analysis, tenofovir AF was noninferior to once-daily tenofovir disoproxil
      fumarate (DF) 300 mg in terms of the proportion of patients achieving viral
      suppression (HBV DNA <29 IU/mL) and was associated with significantly higher
      alanine aminotransferase (ALT) normalization rates than tenofovir DF based on
      AASLD criteria (but not central laboratory criteria). In pooled analyses and/or
      individual trials, ALT normalization rates by AASLD and central laboratory
      criteria were significantly higher in tenofovir AF than tenofovir DF recipients
      at most assessed timepoints up to 96 weeks. Given the bone and renal safety
      concerns associated with long-term tenofovir DF treatment, the more favourable
      pharmacological profile of tenofovir AF permits a marked reduction in the dosage
      of this tenofovir prodrug and thereby reduces systemic exposure to tenofovir,
      potentially improving the bone and renal safety of tenofovir AF versus tenofovir
      DF. Long-term clinical experience will more definitively establish the relative
      bone and renal safety of these tenofovir prodrugs. With its potential for an
      improved safety profile, tenofovir AF is an important emerging first-line option
      for the treatment of chronic HBV infection in adults and adolescents (aged >=12
      years and with a bodyweight of >=35 kg).

PMID- 28493173
TI  - Idiopathic inflammatory myopathy and the risk of venous thromboembolism: a meta
      analysis.
AB  - This study aimed at analyzing published data on the association between
      idiopathic inflammatory myopathy and venous thromboembolism (VTE). We examined
      studies on VTE risk in patients with polymyositis (PM) and/or dermatomyositis
      (DM), in the MEDLINE, EMBASE, and Cochrane databases and via manual searches. We
      performed a meta-analysis on the relative risks (RRs) of VTE, pulmonary embolism
      (PE), and deep vein thrombosis (DVT) in these patients. Five studies, including
      8858 patients with PM/DM met the inclusion criteria. Meta-analysis revealed a
      significant association between PM/DM and VTE risk (RR = 4.364, 95% CI 2.128
      8.949, p = 5.8 * 10-5). A significant association was found between PE risk and
      PM/DM (RR = 3.504, 95% CI 2.856-4.300, p < 1.0 * 10-8). Meta-analysis also
      indicated a significant association between DVT risk and PM/DM (RR = 7.481, 95%
      CI 3.355-16.68, p = 8.7 * 10-7). This meta-analysis demonstrated that both types
      of PM/DM are associated with an elevated risk of VTE, PE, and DVT, suggesting
      that patients with PM/DM should be carefully monitored for development of these
      conditions.

PMID- 28493174
TI  - Genomics, transcriptomics and proteomics to elucidate the pathogenesis of
      rheumatoid arthritis.
AB  - Rheumatoid arthritis is an autoimmune disease that affects several organs and
      tissues, predominantly the synovial joints. The pathogenesis of this disease is
      not completely understood, which maybe involved in the genomic variations, gene
      expression, protein translation and post-translational modifications. These
      system variations in genomics, transcriptomics and proteomics are dynamic in
      nature and their crosstalk is overwhelmingly complex, thus analyzing them
      separately may not be very informative. However, various '-omics' techniques
      developed in recent years have opened up new possibilities for clarifying disease
      pathways and thereby facilitating early diagnosis and specific therapies. This
      review examines how recent advances in the fields of genomics, transcriptomics
      and proteomics have contributed to our understanding of rheumatoid arthritis.

PMID- 28493175
TI  - Treatment for lupus nephritis: an overview of systematic reviews and meta
      analyses.
AB  - The aim is to systematically review the treatment for lupus nephritis (LN) by
      performing an overview of systematic reviews and meta-analyses. Electronic
      databases of OVID MEDLINE, OVID EMBASE, and Cochrane Library were searched to
      identify published systematic reviews and meta-analyses investigating treatments
      for LN up to 13 July 2016. A measurement tool to assess systematic reviews
      (AMSTAR) was used to assess the quality of included studies. Totally, 24 studies
      were included. Of the eligible studies, 3 studies were rated as poor quality, 11
      as moderate, and 10 as good. In LN induction therapy, comparing to
      cyclophosphamide, tacrolimus had higher complete remission rate, response rate,
      and anti-dsDNA negative conversion rate and led to lower risks of
      gastrointestinal symptoms and amenorrhea, and mycophenolate mofetil (MMF) was
      associated with higher response rate and less adverse events of leucopenia,
      alopecia, and ovarian failure. However, there was no difference in the efficacy
      and adverse events between tacrolimus and MMF. In LN maintenance therapy, the
      relapse rate and leucopenia rate were lower in MMF group than in azathioprine
      group, but there were no differences of end-stage kidney disease rate and
      mortality rate between the two groups. For LN induction therapy, both Tacrolimus
      and MMF are more effective and safer than cyclophosphamide, while there are no
      differences of efficacy or safety between the two treatments. For LN maintenance
      therapy, MMF seems to have less adverse events and lower relapse rate than
      azathioprine.

PMID- 28493176
TI  - The Effectiveness of Psychosocial Interventions Delivered by Teachers in Schools:
      A Systematic Review and Meta-Analysis.
AB  - The growing mental health needs of students within schools have resulted in
      teachers increasing their involvement in the delivery of school-based,
      psychosocial interventions. Current research reports mixed findings concerning
      the effectiveness of psychosocial interventions delivered by teachers for mental
      health outcomes. This article presents a systematic review and meta-analysis that
      examined the effectiveness of school-based psychosocial interventions delivered
      by teachers on internalizing and externalizing outcomes and the moderating
      factors that influence treatment effects on these outcomes. Nine electronic
      databases, major journals, and gray literature (e.g., websites, conference
      abstract) were searched and field experts were contacted to locate additional
      studies. Twenty-four studies that met the study inclusion criteria were coded
      into internalizing or externalizing outcomes and further analyzed using robust
      variance estimation in meta-regression. Both publication and risk of bias of
      studies were further assessed. The results showed statistically significant
      reductions in students' internalizing outcomes (d = .133, 95% CI [.002, .263])
      and no statistical significant effect for externalizing outcomes (d = .15, 95% CI
      [-.037, .066]). Moderator analysis with meta-regression revealed that gender
      (%male, b = -.017, p < .05), race (% Caucasian, b = .002, p < .05), and the tier
      of intervention (b = .299, p = .06) affected intervention effectiveness. This
      study builds on existing literature that shows that teacher-delivered Tier 1
      interventions are effective interventions but also adds to this literature by
      showing that interventions are more effective with internalizing outcomes than on
      the externalizing outcomes. Moderator analysis also revealed treatments were more
      effective with female students for internalizing outcomes and more effective with
      Caucasian students for externalizing outcomes.

PMID- 28493177
TI  - What is Single-Payer Health Care? A Review of Definitions and Proposals in the
      U.S.
AB  - BACKGROUND: Single-payer systems have been proposed as a health care reform
      alternative in the United States. However, there is no consensus on the
      definition of single-payer. Most definitions characterize single-payer as one
      entity that collects funds and pays for health care on behalf on an entire
      population. Increased flexibility for state health care reform may provide
      opportunities for state-based single-payer systems to be considered. OBJECTIVE:
      To explore the concept of single-payer and to describe the contents of single
      payer health care proposals. DESIGN: We compared single-payer definitions and
      proposals. We coded the proposal text for provisions that would change how the
      health care system functions and could impact health care access, quality, and
      cost. MAIN MEASURES: The share of proposals that include changes to the
      financing, pooling, purchasing, and delivery of health care; and possible impact
      on access, quality, and costs. KEY RESULTS: We identified 25 proposals for
      national or state single-payer plans from journal and legislative databases. The
      proposals typically call for wide-ranging reform; nearly all include changes
      across the financing, pooling, purchasing, and delivery of health care services.
      Many provisions aiming to improve access, quality, and cost containment are also
      included, but the proposals vary in how they plan to achieve these improvements.
      Common provisions are related to comprehensive benefits, patient choice of
      providers, little or no cost sharing, the role of private insurance, provider
      guidelines and standards, periodic reviews of the benefits package, electronic
      medical records and billing, prescription drug formulary, global budgets,
      administrative cost thresholds, payment reform and studies, and the authority to
      implement cost-containment strategies. CONCLUSIONS: Single-payer systems are
      heterogeneous. Acknowledgment of what is considered as single-payer and the
      characteristics that are variable is important for nuanced policy discussions on
      specific reform proposals.

PMID- 28493178
TI  - Language Barriers, Informed Consent, and Effective Caregiving.

PMID- 28493179
TI  - Where to position osteotomies in genioglossal advancement surgery based on
      locations of the mental foramen, canine, lateral incisor, central incisor, and
      genial tubercle.
AB  - PURPOSE: The study aimed to provide precise measurements of anterior mandibular
      structural anatomy and to explore potential osteotomies for genioglossal
      advancement. METHODS: Cone beam computed tomography was used to analyze 33
      randomly selected patients undergoing surgery for obstructive sleep apnea (OSA)
      between 2014 and 2016 at an academic surgical hospital. The locations of relevant
      mandibular structures were measured and statistical modeling was performed.
      RESULTS: Mean horizontal distances from midline to the mental foramina and the
      roots of the canine, lateral incisor, and central incisor were 22.11 +/- 1.92,
      13.56 +/- 3.01, 6.19 +/- 1.58, and 2.04 +/- 0.87 mm, respectively. Mean vertical
      distances from the inferior border of the mandible were 15.15 +/- 1.77, 17.11 +/-
      3.28, 20.48 +/- 3.10, and 21.81 +/- 3.49 mm, respectively. The superior border of
      the genial tubercle was 15.63 +/- 2.75 mm, and the inferior border was 6.87 +/-
      3.29, from the inferior border of the mandible. The angle of decline of the best
      fit line through the important structures was about 18 degrees  from the
      occlusion plane at the midline. CONCLUSIONS: A straight line estimating the
      mental foramen, canine, lateral incisor, and central incisor tooth roots crosses
      at a mean of 22.3-22.6 mm above the inferior border of the mandible at the
      midline and has an angle of decline of about 18 degrees . Potential osteotomies
      made parallel to and below this line result in tradeoffs between maximizing
      capture of the genioglossus muscle attachment and risk of dental/neurovascular
      injury.

PMID- 28493180
TI  - Erratum to: The Molecular Basis of Evolution and Disease: A Cold War Alliance.

PMID- 28493181
TI  - Assessment of hydrogen sulfide emission from a sewage treatment plant using
      AERMOD.
AB  - Air quality modeling plays an important role in prediction of air pollutants in
      urban areas. Moreover, it is also an essential component to make crucial
      decisions in environmental management. In this study, environmental protection
      agency (EPA) regulatory model (AERMOD) was implemented in order to assess the
      urban air quality in the city of Muscat, Sultanate of Oman. Dispersion modeling
      was employed for the prediction of hydrogen sulfide (H2S) emissions, a
      neighborhood claimed issue, from Al-Ansab sewage treatment plant (STP).
      Meteorological, elevation data, and H2S survey results were implemented into the
      model. From the site survey study, four different H2S emission sources were
      identified as sewage tanker connection points, biofilter, old odor control unit
      (OCU), and open channels of raw sewage. It was observed that based on maximum 24
      h analysis, the ground level concentration outside the STP exceeded the
      concentration limit, 40 MUg/m3, recommended by the local regulating agency in
      Oman. By applying a sensitivity analysis study, the locations with the highest
      predicted H2S levels were identified. The most affected area in the worst-case
      scenario was the nearby expressway with 450.9 MUg/m3 of H2S. The highest ground
      level concentration of H2S was detected in March, while the lowest was measured
      in December. The model also predicted that the impact of odor nuisance is greater
      at the summer season than that of other seasons due to the elevated temperatures.
      The study revealed an adverse environmental impact from the STPs on urban air
      quality, which may pose a threat to the public health.

PMID- 28493182
TI  - Modeling seasonal and spatial contamination of surface waters and upper sediments
      with trace metal elements across industrialized urban areas of the Seybouse
      watershed in North Africa.
AB  - Industrialization and urbanization are the main sources of pollutions worldwide
      and particularly in developing countries. This study aims the determination of
      anthropogenic inputs with trace metals in aquatic ecosystems at the Plain of
      Annaba (NE Algeria), which is known as one of the largest industrial areas in
      Africa. Samples of surface waters and upper sediments were conducted in six
      stations: four in Meboudja wadi and two in Seybouse wadi. Contents of iron,
      copper, chromium, nickel, zinc, and manganese were measured by atomic absorption
      spectrophotometry, whereas Cd and Pb were determined using electrothermal atomic
      absorption spectrometry. Measurements of Hg were carried out using atomic
      fluorescence. Spatiotemporal variations of metal concentrations were tested using
      generalized linear models (GLM), whereas the influence of water pollution on
      sediment contamination was tested with generalized additive models (GAMs). Metal
      contents measured in surface water and sediments varied differently from upstream
      to downstream of the study wadis and between seasons. The results showed that the
      surface water was polluted with high levels of iron, nickel, chromium, lead, and
      cadmium. Values of the contamination index revealed that the surface sediments
      were contaminated by iron, chromium, lead, and cadmium. The GAMs indicated that
      water-phase metal concentrations had no significant effects on trace metal
      concentrations in the sediment. This suggests that seasonal metal concentrations
      in water phase, which are measured during the study period (2012) and are time
      dependent, contribute increasingly and gradually over time-not immediately-to the
      accumulation of metals into the sediments. Therefore, the long-term accumulation
      of metals in the sediments resulted from the continuous discharges of metals in
      the water phase. The anthropogenic impacts are marked by high contaminations of
      Meboudja wadi particularly in downstream areas of the steel factory and the
      nearby industrial areas. The direct industrial discharges into the water and
      atmosphere (iron, lead, cadmium) as well as urban disposals and agricultural
      activities are at the origin of these contaminations.

PMID- 28493183
TI  - Geochemical characterization of fluoride in water, table salt, active sediment,
      rock and soil samples, and its possible relationship with the prevalence of
      enamel fluorosis in children in four municipalities of the department of Huila
      (Colombia).
AB  - Fluoride is an element that affects teeth and bone formation in animals and
      humans. Though the use of systemic fluoride is an evidence-based caries
      preventive measure, excessive ingestion can impair tooth development, mainly the
      mineralization of tooth enamel, leading to a condition known as enamel fluorosis.
      In this study, we investigated the geochemical characterization of fluoride in
      water, table salt, active sediment, rock and soil samples in four endemic enamel
      fluorosis sentinel municipalities of the department of Huila, Colombia (Pitalito,
      Altamira, El Agrado and Rivera), and its possible relationship with the
      prevalence of enamel fluorosis in children. The concentration of fluoride in
      drinking water, table salt, active sediment, rock, and soil was evaluated by
      means of an ion selective electrode and the geochemical analyses were performed
      using X-ray fluorescence. Geochemical analysis revealed fluoride concentrations
      under 15 mg/kg in active sediment, rock and soil samples, not indicative of a
      significant delivery to the watersheds studied. The concentration of fluoride in
      table salt was found to be under the inferior limit (less than 180 MUg/g)
      established by the Colombian regulations. Likewise, exposure doses for fluoride
      water intake did not exceed the recommended total dose for all ages from 6
      months. Although the evidence does not point out at rocks, soils, fluoride
      bearing minerals, fluoridated salt and water, the hypothesis of these elements as
      responsible of the current prevalence of enamel fluorosis cannot be discarded
      since, aqueducts might have undergone significant changes overtime.

PMID- 28493184
TI  - The Moderating Role of Spirituality in the Association between Stress and
      Substance Use among Adolescents: Differences by Gender.
AB  - Adolescents are exposed to various stressors that may increase the risk for
      substance use. Due to the detrimental, and potentially long-lasting, effects
      related to substance use, it is necessary to explore more optimal coping
      strategies. This study explored the association between substance use and stress
      among male and female high school students in relation to spirituality as a
      moderator. To examine these relationships, the study used cross-sectional data
      collected from 27,874 high school students (Male = 50.7%, Female = 49.3%) across
      58 high schools in Maryland that included an ethnically diverse sample (49%
      Caucasian, 30% African American) with an average age of 16 years old. Bivariate
      results showed differences in substance use, stress, and spirituality between
      male and female students. Higher rates of substance use were generally found
      among male students compared to female students; rates tended to be higher among
      female students for stress and spirituality compared to their male counterparts.
      Multilevel analyses indicated a positive association between stress and substance
      use among male and female students after adjusting for demographic and school
      level factors. Both male and female students who reported turning to spiritual
      beliefs when experiencing problems were less likely to use substances. However,
      the interaction between stress and spirituality was significant for males only.
      These findings suggest that stress may increase the propensity for substance use
      and that spirituality might be a viable coping mechanism useful for helping high
      school students adapt to stressful circumstances and situations.

PMID- 28493185
TI  - Dietary PUFA Increase Apoptosis in Stomach of Patients with Dyspeptic Symptoms
      and Infected with H. pylori.
AB  - Drug-resistant strains of Helicobacter pylori and poor treatment response are the
      main reasons for the failure in eradicating it in patients. Polyunsaturated fatty
      acids (PUFA) have an inhibitory effect on bacterial growth. The aim of this study
      was to investigate the effect of PUFA in combination with standard triple therapy
      on apoptosis in H. pylori infected subjects with dyspeptic symptoms. This study
      was a double-blind clinical trial in which 34 H. pylori infected subjects with
      dyspeptic symptoms were randomly divided into two groups of 17 patients. The
      control group received standard triple therapy (amoxicillin, clarithromycin and
      omeprazole) and the experimental group received the standard therapy and PUFA for
      two weeks. Gene expression levels of caspase-3, BCL-2 and Bad proteins were
      studied with real-time PCR, while protein levels were quantified in frozen
      sections and using immunohistochemistry. Compared with the control group, a
      significant increase (p < 0.01) was observed in the expression of caspase-3 and
      Bad genes and a significant reduction (p < 0.05) in the expression of Bcl-2 gene.
      The protein level of active caspase-3 and Bad protein was significantly increased
      and the level of Bcl-2 protein was significantly decreased (p < 0.05). The
      results of this study show that oral administration of PUFA in combination with
      the standard triple therapy increased apoptosis in H. pylori-infected patients
      with dyspeptic symptoms. This increase in apoptosis may partly reduce drug
      resistance in these patients. Our results suggest inclusion of a dietary PUFA
      containing fatty acid supplement may improve treatment of patients that are
      refractory to the standard triple therapy.

PMID- 28493186
TI  - Analysis of ecotoxic influence of waste from the biomass gasification process.
AB  - The purpose of this research was evaluation of the effect of soil contamination
      with waste coming from biomass gasification on chosen indicators of its
      biological activity, growth and development of spring barley, and change of
      physiological parameters of the plant. Chromatographic content and basic
      rheological parameters of the substances under research were also analyzed.
      Liquid wastes, tar, and mixture of tar and engine oil were introduced to the soil
      in the amount of 100 mg kg-1 DM soil. Based on the conducted research, it was
      ascertained that the changes in the number and activity of soil microorganisms
      were determined by the type of waste and its dose. Individual groups of
      microorganisms showed different sensitivity to the presence of pollution;
      however, the impact of tar and engine oil mixture was generally more
      disadvantageous. Presence of contaminants in the soil limited the growth of roots
      and aboveground parts of spring barley, especially when the dose was 10,000 mg kg
      1 DM soil. The unfavorable impact of waste on photosynthesis efficiency on
      assimilation pigment synthesis and water content in the plant was recorded.

PMID- 28493188
TI  - Are renewable energy policies upsetting carbon dioxide emissions? The case of
      Latin America countries.
AB  - The impact of renewable energy policies in carbon dioxide emissions was analysed
      for a panel of ten Latin American countries, for the period from 1991 to 2012.
      Panel autoregressive distributed lag methodology was used to decompose the total
      effect of renewable energy policies on carbon dioxide emissions in its short- and
      long-run components. There is evidence for the presence of cross-sectional
      dependence, confirming that Latin American countries share spatial patterns.
      Heteroskedasticity, contemporaneous correlation, and first-order autocorrelation
      cross-sectional dependence are also present. To cope with these phenomena, the
      robust dynamic Driscoll-Kraay estimator, with fixed effects, was used. It was
      confirmed that the primary energy consumption per capita, in both the short- and
      long-run, contributes to an increase in carbon dioxide emissions, and also that
      renewable energy policies in the long-run, and renewable electricity generation
      per capita both in the short- and long-run, help to mitigate per capita carbon
      dioxide emissions.

PMID- 28493187
TI  - The short-term associations of weather and air pollution with emergency ambulance
      calls for paroxysmal atrial fibrillation.
AB  - A circadian variation in the cardiovascular parameters has been detected. It is
      plausible that the influence of the environment varies during different periods
      of the day. We investigated the association between daily emergency ambulance
      calls (EC) for paroxysmal atrial fibrillation (AF) that occurred during the time
      intervals of 8:00-13:59, 14:00-21:59, and 22:00-7:59, and weather conditions and
      exposure to CO and PM10. We used Poisson regression to explore the association
      between the risk of EC for AF and environmental variables, adjusting for seasonal
      variation. Before noon, the risk was associated with an IQR (0.333 mg/m3)
      increase in CO at lag 2-6 days above the median (RR = 1.15, P = 0.002); a
      protective impact of CO on previous day was observed (RR = 0.91, P = 0.018).
      During 14:00-21:59, a negative effect of air temperature below 1.9  degrees C
      (lag 2-3 days) was detected (per 10  degrees C decrease: RR = 1.17, P = 0.044).
      At night, the elevated risk was associated with wind speed above the median (lag
      2-4 days) (per 1-kt increase: RR = 1.07, P = 0.001) and with PM10 at lag 2-5 days
      below the median (per IQR (7.31 MUg/m3) increase: RR = 1.21, P = 0.002).
      Individuals over 65 years of age were more sensitive to air pollution, especially
      at night (CO lag 2-3 days < median, per IQR (0.12 mg/m3) increase: RR = 1.14, P =
      0.045; PM10 lag 2-5 days < median, per IQR increase: RR = 1.32, P = 0.001). The
      associations of air pollution and other environmental variables with acute events
      may be analyzed depending on the time of the event.

PMID- 28493189
TI  - The treatment of wastewater containing pharmaceuticals in microcosm constructed
      wetlands: the occurrence of integrons (int1-2) and associated resistance genes
      (sul1-3, qacEDelta1).
AB  - The aim of this study was to analyze the occurrence of sulfonamide resistance
      genes (sul1-3) and other genetic elements as antiseptic resistance gene
      (qacEDelta1) and class 1 and class 2 integrons (int1-2) in the upper layer of
      substrate and in the effluent of microcosm constructed wetlands (CWs) treating
      artificial wastewater containing diclofenac and sulfamethoxazole (SMX), which is
      a sulfonamide antibiotic. The bacteria in the substrate and in the effluents were
      equipped with the sul1-2, int1, and qacEDelta1 resistance determinants, which
      were introduced into the CW system during inoculation with activated sludge and
      with the soil attached to the rhizosphere of potted seedlings of Phalaris
      arundinacea 'Picta' roots (int1). By comparing the occurrence of the resistance
      determinants in the upper substrate layer and the effluent, it can be stated that
      they neither were lost nor emerged along the flow path. The implications of the
      presence of antibiotic resistance genes in the effluent may entail a risk of
      antibiotic resistance being spread in the receiving environment. Additionally,
      transformation products of SMX were determined. According to the obtained
      results, four (potential) SMX transformation products were identified. Two major
      metabolites of SMX, 2,3,5-trihydroxy-SMX and 3,5-dihydroxy-SMX, indicated that
      SMX may be partly oxidized during the treatment. The remaining two SMX
      transformation products (hydroxy-glutathionyl-SMX and glutathionyl-SMX) are
      conjugates with glutathione, which suggests the ability of CW bacterial community
      to degrade SMX and resist antimicrobial stress.

PMID- 28493190
TI  - Preparation of a new Fenton-like catalyst from red mud using molasses wastewater
      as partial acidifying agent.
AB  - Using molasses wastewater as partial acidifying agent, a new Fenton-like catalyst
      (ACRM sm ) was prepared through a simple process of acidification and calcination
      using red mud as main material. With molasses wastewater, both the free alkali
      and the chemically bonded alkali in red mud were effectively removed under the
      action of H2SO4 and molasses wastewater, and the prepared ACRM sm was a near
      neutral catalyst. The ACRM sm preparation conditions were as follows: for 3 g of
      red mud, 9 mL of 0.7 mol/L H2SO4 plus 2 g of molasses wastewater as the
      acidifying agent, calcination temperature 573 K, and calcination time 1 h. Iron
      phase of ACRM sm was mainly alpha-Fe2O3 and trace amount of carbon existed in
      ACRM sm . The addition of molasses wastewater not only effectively reduced the
      consumption of H2SO4 in acidification of red mud but also resulted in the
      generation of carbon and significantly improved the distribution of macropore in
      prepared ACRM sm . It was found that near-neutral pH of catalyst, generated
      carbon, and wide distribution of macropore were the main reasons for the high
      catalytic activity of ACRM sm . The generated carbon and wide distribution of
      macropore were entirely due to the molasses wastewater added. In degradation of
      orange II, ACRM sm retained most of its catalytic stability and activity after
      five recycling times, indicating ACRM sm had an excellent long-term stability in
      the Fenton-like process. Furthermore, the performance test of settling showed
      ACRM sm had an excellent settleability. ACRMsm was a safe and green catalytic
      material used in Fenton-like oxidation for wastewater treatment.

PMID- 28493191
TI  - Distribution and variation of mercury in frozen soils of a high-altitude
      permafrost region on the northeastern margin of the Tibetan Plateau.
AB  - The Tibetan Plateau (TP) is home to the largest permafrost bodies at low- and mid
      latitudes, yet little is known about the distribution and variation of mercury
      (Hg) in frozen soil of the permafrost regions. In this study, extensive soil
      sampling campaigns were carried out in 23 soil pits from 12 plots in a high
      altitude permafrost region of the Shule River Basin, northeastern TP. Hg
      distribution, variation, and their dependences on soil properties were analyzed.
      The results have revealed that total Hg (THg) concentrations were low ranging
      from 6.3 to 29.1 ng g-1. A near-surface peak of THg concentrations followed by a
      continuous decrease were observed on the vertical profiles of most soil pits.
      Significant positive relationships among THg concentrations, soil organic carbon
      (SOC) contents, and silty fractions were observed, indicating that SOC content
      and silty fraction are two dominant factors influencing the spatial distribution
      of THg. THg concentrations in soils showed a decreasing trend with altitude,
      which was probably attributed to a lower soil potential to Hg accumulation under
      the condition of lower SOC contents and silty fractions at high altitudes.
      Approximately, 130.6 t Hg in soils (0-60 cm) was estimated and a loss of 64.2% of
      Hg from the highly stable and stable permafrost (H-SP) region via permafrost
      degradation was expected in the upstream regions of the Shule River Basin,
      indicating that the large areas of permafrost regions may become an important
      source of global Hg emission as a result of the ongoing widespread permafrost
      degradation.

PMID- 28493192
TI  - Simulating water and nitrogen loss from an irrigated paddy field under
      continuously flooded condition with Hydrus-1D model.
AB  - Agricultural non-point source pollution is a major factor in surface water and
      groundwater pollution, especially for nitrogen (N) pollution. In this paper, an
      experiment was conducted in a direct-seeded paddy field under traditional
      continuously flooded irrigation (CFI). The water movement and N transport and
      transformation were simulated via the Hydrus-1D model, and the model was
      calibrated using field measurements. The model had a total water balance error of
      0.236 cm and a relative error (error/input total water) of 0.23%. For the solute
      transport model, the N balance error and relative error (error/input total N)
      were 0.36 kg ha-1 and 0.40%, respectively. The study results indicate that the
      plow pan plays a crucial role in vertical water movement in paddy fields. Water
      flow was mainly lost through surface runoff and underground drainage, with
      proportions to total input water of 32.33 and 42.58%, respectively. The water
      productivity in the study was 0.36 kg m-3. The simulated N concentration results
      revealed that ammonia was the main form in rice uptake (95% of total N uptake),
      and its concentration was much larger than for nitrate under CFI. Denitrification
      and volatilization were the main losses, with proportions to total consumption of
      23.18 and 14.49%, respectively. Leaching (10.28%) and surface runoff loss (2.05%)
      were the main losses of N pushed out of the system by water. Hydrus-1D simulation
      was an effective method to predict water flow and N concentrations in the three
      different forms. The study provides results that could be used to guide water and
      fertilization management and field results for numerical studies of water flow
      and N transport and transformation in the future.

PMID- 28493193
TI  - The first survey of airborne trace elements at airport using moss bag technique.
AB  - Air traffic represents an important way of social mobility in the world, and many
      ongoing discussions are related to the impacts that air transportation has on
      local air quality. In this study, moss Sphagnum girgensohnii was used for the
      first time in the assessment of trace element content at the international
      airport. The moss bags were exposed during the summer of 2013 at four sampling
      sites at the airport 'Nikola Tesla' (Belgrade, Serbia): runway (two), auxiliary
      runway and parking lot. According to the relative accumulation factor (RAF) and
      the limit of quantification of the moss bag technique (LOQT), the most abundant
      elements in the samples were Zn, Na, Cr, V, Cu and Fe. A comparison between the
      element concentrations at the airport and the corresponding values in different
      land use classes (urban central, suburban, industrial and green zones) across the
      city of Belgrade did not point out that the air traffic and associated activities
      significantly contribute to the trace element air pollution. This study
      emphasised an easy operational and robust (bio)monitoring, using moss bags as a
      suitable method for assessment of air quality within various microenvironments
      with restriction in positioning referent instrumental devices.

PMID- 28493194
TI  - Effectiveness of quercetin in an experimental rat model of allergic rhinitis.
AB  - We aimed to investigate whether quercetin had a therapeutic effect in an
      experimental rat model of allergic rhinitis. The study was conducted with 35
      rats, which were randomly assigned into 4 groups: group 1 (n = 5), sham group;
      group 2 (quercetin group, n = 10) received 80 mg/kg day quercetin; group 3
      (steroid group, n = 10) received steroid (mometasone furoate); and group 4
      (control group, n = 10), received ovalbumin alone. Rats were sensitized by
      administration of ovalbumin on alternate days over 14 days via an intraperitoneal
      route. On day 15, in addition to ovalbumin via an intranasal route, quercetin and
      steroid were given over 7 days to the corresponding groups. All rats were then
      sacrificed and nasal turbinates were evaluated histopathologically, and serum
      total IgE and ovalbumin (OVA)-specific IgE values were measured before and after
      treatment. A significant increase in OVA-specific IgE values was detected in all
      groups except sham group. A significant increase was detected in post-treatment
      total IgE levels in the control group, while no significant change was detected
      in the sham, quercetin, and intranasal steroid groups. On histopathological
      evaluation, it was observed that findings of allergic rhinitis were suppressed in
      the quercetin group when compared to the control group. In immunohistochemical
      evaluation, it was detected that COX-2 and VIP expressions were weaker in the
      quercetin group compared to the control group. Based on these findings, we
      conclude that quercetin was effective in allergic rhinitis induced by ovalbumin
      in rats both histopathologically and serologically.

PMID- 28493195
TI  - uDISE model: a universal drug-induced sedation endoscopy classification system
      part 1.
AB  - Drug-induced sedation endoscopy (DISE) classification systems play a significant
      role in clinical analysis based on DISE findings, treatment decision process,
      treatment planning process and fundamentally in treatment outcomes. However,
      there is a major problem: there is no universally agreed DISE classification
      system. Hence, for the same DISE examination different DISE classification
      systems can be used to: assess anatomic findings, decide and plan different
      treatments. Hence, this leads to different treatment outcomes. The key objective
      of this study is to propose uDISE model: universal drug-induced sedation
      endoscopy (DISE) classification system. Set theory and relational mapping was
      used to develop a DISE classification system based on anatomical
      structures/level; degree of severity; and configuration of obstruction and its
      relationship with existing DISE classification systems. uDISE model consists of
      seven anatomical sites (nose, velum, tonsils, lateral pharyngeal wall/oropharynx,
      tongue base, epiglottis and larynx), three degrees of obstructive severity (none,
      partial and complete), three configurations of obstruction (anteroposterior,
      lateral and circumferential) and a severity index. uDISE model was mapped to four
      existing DISE classification systems: Pringle and Croft grading system, VOTE,
      NOHL and P-T-L-Tb-E. uDISE model provides a methodology for mapping different
      DISE findings based on different classification systems into one common DISE
      assessments format. This provides a framework for comparing different DISE
      assessments, treatment plan and treatment outcome irrespective of DISE
      classification system used. Further research is required to establish a complete
      relational mapping between uDISE model and other existing DISE classification
      systems.

PMID- 28493196
TI  - Head and neck reconstruction in the elderly patient: a safe procedure?
AB  - Demographic changes strongly affect industrialized countries. While free tissue
      transfer was initially believed to be beneficial only for younger patients, there
      is an increasing number of elderly patients requiring microvascular operations in
      our aging society. Medical and surgical risks for head and neck cancer patients
      over a certain age who undergo free tissue transfer has hardly been investigated.
      A retrospective mono-center cohort study was performed. All patients with the age
      75 or higher undergoing microvascular operations were reviewed. Patient
      characteristics including the ASA-status, the ACE-27-score, flap survival and
      postoperative medical and surgical complications were evaluated. The Clavien
      Dindo-classification system for postoperative complications was applied to assess
      the severity of the complications. A total of 31 patients with an average age of
      78.8 years were included. 4 patients suffered from venous congestion and had to
      undergo revision surgery. All flaps could successfully be salvaged. Higher ASA
      status and ACE-score were significantly associated with postoperative medical and
      surgical complications and a higher severity of the complications. However ,
      neither age nor operating time had influence on the complication rate.
      Microvascular free tissue transfer can be performed with a high degree of
      security in selected elderly patients. However, serious medical complications
      remain a concern, correlating strongly with high ASA and ACE-score. Careful
      patient selection is mandatory to reduce complications to a minimum.

PMID- 28493197
TI  - Risk factors for ventilator-associated pneumonia among patients undergoing major
      oncological surgery for head and neck cancer.
AB  - Patients undergoing major oncological surgery for head and neck cancer (SHNC)
      have a particularly high risk of nosocomial infections. We aimed to identify risk
      factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC.
      The study included 465 patients who underwent SHNC between June 2011 and June
      2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were
      retrospectively evaluated. The incidence of VAP was 19.6% (n = 95) in patients
      who required more than 48 h of mechanical ventilation. Staphylococcus (37.7%),
      Enterobacteriaceae (32.1%), Pseudomonas (20.8%), and Haemophilus (16.9%) were the
      major bacterial species that caused VAP. The independent risk factors for VAP
      were advanced age, current smoking status, chronic obstructive pulmonary disease,
      and a higher simplified acute physiology score system II upon admission.
      Tracheostomy was an independent protective factor for VAP. The median length of
      stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days,
      respectively (P = 0.006). Mortality among patients who did or did not develop VAP
      was 16.8% and 8.4%, respectively (P < 0.001). The potential economic impact of
      VAP was high because of the significantly extended duration of ventilation. A
      predictive regression model was developed with a sensitivity of 95.3% and a
      specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who
      require more than 48 h of mechanical ventilation. Therefore, innovative
      preventive measures should be developed and applied in this high-risk population.

PMID- 28493198
TI  - Risk factors of prognosis after acute kidney injury in hospitalized patients.
AB  - The risk factors, especially laboratory indicators, of prognosis after acute
      kidney injury (AKI) remain unclear. We conducted a retrospective survey of
      Chinese People's Liberation Army General Hospital from January 1, 2012 to
      December 31, 2012 according to the AKI diagnosis standard issued by Kidney
      Disease Improving Global Outcomes. The epidemiological features and factors
      influencing hospital mortality and renal function recovery were evaluated through
      logistic regression analysis. Among 77 662 cases of hospitalized patients, 1387
      suffered from AKI. The incidence rate and mortality of AKI were 1.79% and 14.56%,
      respectively. Multivariate logistic regression analysis revealed that high AKI
      stage, age greater than 80 years, neoplastic disease, low cardiac output,
      increased white blood cell count, and decreased platelet count and serum albumin
      levels were the risk factors affecting the mortality of AKI patients. Conversely,
      body mass index between 28 and 34.9 was a protective factor. Increased AKI stage,
      tumor disease, post-cardiopulmonary resuscitation, and RRT were the risk factors
      of renal function recovery upon discharge. In addition to traditional risk
      factors, white blood cell count, platelet count, albumin, and BMI were the
      predictors of the mortality of AKI patients. No laboratory indicators were found
      to be the risk factors of renal function recovery in AKI patients.

PMID- 28493199
TI  - Selenium-Chromium(VI) Interaction Regulates the Contents and Correlations of
      Trace Elements in Chicken Brain and Serum.
AB  - This study aims to investigate the contents of trace elements in the brain and
      serum of male chickens and the effect of selenium-chromium(VI) interaction. A
      chronic experimental model was established by supplementing 22.14 mg/kg K2Cr2O7
      with 0.00, 0.31, 0.63, 1.25, 2.50, and 5.00 mg/kg Na2SeO3 mg/kg B.W. to water for
      chicken daily. After 14, 28, and 42 days of exposure to the solution, the brain
      and serum of chickens from each group were collected to detect the levels of Ca,
      Cu, Mn, Fe, Zn, and Mg by inductively coupled plasma mass spectrometer (ICP-MS).
      Cr(VI) time-dependently accumulated in the brain and serum. The contents of Cr
      increased both in the brain and serum with prolonged exposure. Cr contents in the
      brain and serum decreased in all Se groups compared with those in only Cr-treated
      groups. Ca contents decreased with prolonged exposure and increasing Se dosage.
      The contents of Cu and Mn increased on the 28th day but decreased on the 42nd day
      in the brain and serum. Fe and Zn contents decreased in the serum under prolonged
      exposure and increased on the 28th day but decreased on the 42nd day in the
      brain. Cr exposure did not significantly affect Mg contents in the brain but
      slightly decreased those in the serum. Therefore, appropriate doses of Se
      affected Cr accumulation, leading to adjustments in the contents and correlations
      of trace elements.

PMID- 28493200
TI  - Reducing radiation exposure from nuclear myocardial perfusion imaging: Time to
      act is now.

PMID- 28493201
TI  - Nuclear cardiology practice in Spain.
AB  - BACKGROUND: In Spain, nuclear cardiology (NC) procedures represent the second
      most frequently performed studies in nuclear medicine (NM) centers. METHODS: The
      NC Working Group of the Spanish Society of Nuclear Medicine and Molecular Imaging
      invited NM departments across the country to answer an online questionnaire
      regarding 2014 activity. RESULTS: Data on 40,161 patients from 42 centers were
      collected. The responding public centers served 39% of Spain's population. The
      estimated NC activity for public hospitals was 2 studies/1,000 population/year.
      Of all the NC procedures, 69% were SPECT myocardial perfusion imaging (MPI), 17%
      equilibrium ventriculography, 12% 18F-FDG PET, 1.3% first pass ventriculography,
      and <1% innervation and amyloidosis imaging, respectively. The most frequent NC
      study was a 99mTc tracer, exercise, 2-day MPI ECG-gated SPECT ordered by a
      cardiologist for diagnosis in an outpatient with 21 days of mean waiting time,
      the stress phase being supervised by both a cardiologist and a NM physician, with
      a NM physician writing a complete report. CONCLUSIONS: A major challenge for NC
      in Spain is the gradual adoption of high-sensitivity, low-dose-dedicated cardiac
      SPECT cameras and the broadening of cardiac PET utilization with more cameras,
      and the availability of MPI tracers alongside the viability/inflammation setup.

PMID- 28493202
TI  - Is measurement of renal function necessary for all trauma patients before
      iodinated contrast administration?
AB  - PURPOSE: The purpose of this study was to identify factors at the time of
      presentation which could quickly exclude or identify renal dysfunction in blunt
      trauma patients, thus negating serum measurement of renal function prior to
      contrast-enhanced imaging and expediting care. METHODS: Patients, >18 years old,
      without renal failure, presenting after blunt trauma, with serum creatinine
      measured at presentation, were retrospectively studied at a single center.
      Variables recorded at presentation including vitals, mechanism, and past medical
      history were analyzed using multivariate regression analysis to identify
      independent predictors of abnormal renal function. RESULTS: From 2009 to 2015, a
      total of 1099 patients met the inclusion criteria. Of those, 75 (6.8%) had renal
      dysfunction at presentation. Patients with renal dysfunction had a mean age of
      74.3 (SD 15.5) years old, and 57.3% were male. Multivariate analysis identified
      independent predictors of renal dysfunction at presentation as age >= 61 (p <
      0.001), hypotension (p = 0.02), and diabetes (p = 0.02). The presence of a single
      identified factor had an 85% sensitivity for renal dysfunction and a 98.5%
      negative predictive value. CONCLUSIONS: Impaired renal function at presentation
      was infrequent in our trauma cohort. Trauma patients who were normotensive, under
      the age of 61, and without diabetes were unlikely to have impaired renal function
      at presentation. In the urgent setting of trauma, patients without these
      comorbidities are likely safe to forgo screening of renal function prior to
      contrast-enhanced imaging.

PMID- 28493204
TI  - Analysis of molecular and (di)atomic dual-descriptor functions and matrices.
AB  - In this work, the dual-descriptor is studied in matrix form [Formula: see text]
      and both coordinates condensed to atoms, resulting in atomic and diatomic (or
      where applicable, bond) condensed single values. This double partitioning method
      of the dual-descriptor matrix is proposed within the Hirshfeld-I atoms-in
      molecule framework although it is easily extended to other atoms-in-molecules
      methods. Diagonalizing the resulting atomic and bond dual-descriptor matrices
      gives eigenvalues and eigenvectors describing the reactivity of atoms and bonds.
      The dual-descriptor function is the diagonal element of the underlying matrix.
      The extra information contained in the atom and bond resolution is highlighted
      and the effect of choosing either the fragment of molecular response or response
      of molecular fragment approach is quantified. Graphical Abstract Atom and bond
      condensed dual descriptor matrices and functions are derived from molecular ones
      using Hirshfeld-I atoms in molecules weight functions.

PMID- 28493203
TI  - Dissection of broad-spectrum resistance of the Thai rice variety Jao Hom Nin
      conferred by two resistance genes against rice blast.
AB  - BACKGROUND: Rice (Oryza sativa) is one of the most important food crops in the
      world. Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of
      the most destructive rice diseases worldwide. To effectively cope with this
      problem, the use of rice blast resistance varieties through innovative breeding
      programs is the best strategy to date. The Thai rice variety Jao Hom Nin (JHN)
      showed broad-spectrum resistance against Thai rice blast isolates. Two QTLs for
      blast resistance in JHN were reported on chromosome 1 (QTL1) and 11 (QTL11).
      RESULTS: Monogenic lines of QTL1 (QTL1-C) and QTL11 (QTL11-C) in the CO39 genetic
      background were generated. Cluster analysis based on the disease reaction pattern
      of QTL1-C and QTL11-C, together with IRBLs, showed that those two monogenic lines
      were clustered with IRBLsh-S (Pish) and IRBL7-M (Pi7), respectively. Moreover,
      sequence analysis revealed that Pish and Pi7 were embedded within the QTL1 and
      QTL11 delimited genomic intervals, respectively. This study thus concluded that
      QTL1 and QTL11 could encode alleles of Pish and Pi7, designated as Pish-J and Pi7
      J, respectively. To validate this hypothesis, the genomic regions of Pish-J and
      Pi7-J were cloned and sequenced. Protein sequence comparison revealed that Pish-J
      and Pi7-J were identical to Pish and Pi7, respectively. The holistic disease
      spectrum of JHN was found to be exactly attributed to the additive ones of both
      QTL1-C and QTL11-C. CONCLUSION: JHN showed broad spectrum resistance against Thai
      and Philippine rice blast isolates. As this study demonstrated, the combination
      of two resistance genes, Pish-J and Pi7-J, in JHN, with each controlling broad
      spectrum resistance to rice blast disease, explains the high level of resistance.
      Thus, the combination of Pish and Pi7 can provide a practical scheme for breeding
      durable resistance in rice against rice blast disease.

PMID- 28493206
TI  - Switching Effects in Molecular Electronic Devices.
AB  - The creation of molecular electronic switches by using smart molecules is of
      great importance to the field of molecular electronics. This requires a
      fundamental understanding of the intrinsic electron transport mechanisms, which
      depend on several factors including the charge transport pathway, the molecule
      electrode coupling strength, the energy of the molecular frontier orbitals, and
      the electron spin state. On the basis of significant progresses achieved in both
      experiments and theory over the past decade, in this review article we focus on
      new insights into the design and fabrication of different molecular switches and
      the corresponding switching effects, which is crucial to the development of
      molecular electronics. We summarize the strategies developed for single-molecule
      device fabrication and the mechanism of these switching effects. These analyses
      should be valuable for deeply understanding the switching effects in molecular
      electronic devices.

PMID- 28493205
TI  - Development of the life impact burn recovery evaluation (LIBRE) profile:
      assessing burn survivors' social participation.
AB  - PURPOSE: Measuring the impact burn injuries have on social participation is
      integral to understanding and improving survivors' quality of life, yet there are
      no existing instruments that comprehensively measure the social participation of
      burn survivors. This project aimed to develop the Life Impact Burn Recovery
      Evaluation Profile (LIBRE), a patient-reported multidimensional assessment for
      understanding the social participation after burn injuries. METHODS: 192
      questions representing multiple social participation areas were administered to a
      convenience sample of 601 burn survivors. Exploratory factor analysis and
      confirmatory factor analysis (CFA) were used to identify the underlying structure
      of the data. Using item response theory methods, a Graded Response Model was
      applied for each identified sub-domain. The resultant multidimensional LIBRE
      Profile can be administered via Computerized Adaptive Testing (CAT) or fixed
      short forms. RESULTS: The study sample included 54.7% women with a mean age of
      44.6 (SD 15.9) years. The average time since burn injury was 15.4 years (0-74
      years) and the average total body surface area burned was 40% (1-97%). The CFA
      indicated acceptable fit statistics (CFI range 0.913-0.977, TLI range 0.904
      0.974, RMSEA range 0.06-0.096). The six unidimensional scales were named:
      relationships with family and friends, social interactions, social activities,
      work and employment, romantic relationships, and sexual relationships. The
      marginal reliability of the full item bank and CATs ranged from 0.84 to 0.93,
      with ceiling effects less than 15% for all scales. CONCLUSIONS: The LIBRE Profile
      is a promising new measure of social participation following a burn injury that
      enables burn survivors and their care providers to measure social participation.

PMID- 28493208
TI  - In memory of Professor Aldo Isidori.

PMID- 28493207
TI  - New Azulene-Type Sesquiterpenoids from the Fruiting Bodies of Lactarius
      deliciosus.
AB  - In the 1H NMR-guided fractionation of extracts from the edible mushroom Lactarius
      deliciosus, two new azulene-type sesquiterpenoids, 7-isopropenyl-4-methyl-azulene
      1-carboxylic acid (1) and 15-hydroxy-3,6-dihydrolactarazulene (2), together with
      seven known compounds were characterized. Their structures were determined on
      basis of spectroscopic evidence, as well as by comparing with literature data.
      Amongst the known metabolites, the 13C NMR assignment of 15-hydroxy-6,7
      dihydrolactarazulene (3) is reported here for the first time. Moreover, 7-acetyl
      4-methylazulene-1-carbaldehyde (5) displayed a moderate antibacterial activity
      against Staphylococcus aureus. *Digital image of L. deliciosus. Retrieved March
      17, 2017 from
      https://upload.wikimedia.org/wikipedia/commons/e/e3/Lactarius_deliciosus_1_(1).jp
      .

PMID- 28493209
TI  - Erratum, corrigenda et emendatio or "mistake, correction and amendment".

PMID- 28493210
TI  - In search of the optimal wound dressing material following total hip and knee
      arthroplasty: a systematic review and meta-analysis.
AB  - BACKGROUND: Various types of dressing materials are available for wound care
      following hip and knee arthroplasty. However, it is unclear if one material is
      more beneficial than the others in terms of wound complications and fluid
      handling capacity. RESEARCH QUESTIONS: We performed a meta-analysis of randomized
      controlled trials comparing alternative wound dressing materials for the post
      operative management of wounds following THA and TKA with respect to (1)
      incidence of wound complications including infection and (2) fluid handling
      capacity. METHODS: Randomized controlled trials comparing alternative dressing
      materials, for post-operative management of wounds following TKA and THA were
      included in the review. Databases searched included the MEDLINE and the EMBASE
      from inception to February 2017. Two authors performed study selection, risk of
      bias assessment and data extraction. Where levels of clinical and statistical
      heterogeneity permitted, data were pooled for meta-analysis. RESULTS: Twelve
      randomized trials with data for the primary outcome were identified. Data were
      available for meta-analysis for two comparisons. Wounds managed with film
      dressings (odds ratio, 0.35; 95% confidence interval [CI], 0.21-0.57) or with
      hydrofiber dressings (odds ratio, 0.28; 95% confidence interval [CI], 0.20-0.40)
      were significantly less likely to have wound complications than those managed
      with passive dressings. There was no evidence that any dressing significantly
      reduced surgical-site infection rates compared with any other dressing.
      Hydrofibre dressings showed better fluid handling capacity than passive dressings
      in terms of mean number of dressing changes (mean difference 1.36; 95% confidence
      interval [CI], 0.15-2.57) and number of patients requiring early dressing change
      (odds ratio, 8.60; 95% confidence interval [CI], 4.68-15.83). CONCLUSION: The
      evidence available in the current literature suggests that advanced dressings
      such as film and Hydrofibre dressings have fewer wound complications and better
      fluid handling capacity. However, insufficient evidence is available to determine
      whether the use of these advanced dressings reduce periprosthetic joint
      infection.

PMID- 28493212
TI  - Composite Bioscaffolds Incorporating Decellularized ECM as a Cell-Instructive
      Component Within Hydrogels as In Vitro Models and Cell Delivery Systems.
AB  - Decellularized tissues represent promising biomaterials, which harness the innate
      capacity of the tissue-specific extracellular matrix (ECM) to direct cell
      functions including stem cell proliferation and lineage-specific differentiation.
      However, bioscaffolds derived exclusively from decellularized ECM offer limited
      versatility in terms of tuning biomechanical properties, as well as cell-cell and
      cell-ECM interactions that are important mediators of the cellular response. As
      an alternative approach, in the current chapter we describe methods for
      incorporating cryo-milled decellularized tissues as a cell-instructive component
      within a hydrogel carrier designed to crosslink under mild conditions. This
      composite strategy can enable in situ cell encapsulation with high cell
      viability, allowing efficient seeding with a homogeneous distribution of cells
      and ECM. Detailed protocols are provided for the effective decellularization of
      human adipose tissue and porcine auricular cartilage, as well as the cryo-milling
      process used to generate the ECM particles. Further, we describe methods for
      synthesizing methacrylated chondroitin sulphate (MCS) and for performing UV
      initiated and thermally induced crosslinking to form hydrogel carriers for
      adipose and cartilage regeneration. The hydrogel composites offer great
      flexibility, and the hydrogel phase, ECM source, particle size, cell type(s) and
      seeding density can be tuned to promote the desired cellular response. Overall,
      these systems represent promising platforms for the development of tissue
      specific 3-D in vitro cell culture models and in vivo cell delivery systems.

PMID- 28493211
TI  - What mechanisms are associated with tibial component failure after kinematically
      aligned total knee arthroplasty?
AB  - PURPOSE: Eight patients treated with kinematically-aligned (KA) total knee
      arthroplasty (TKA) presented with tibial component failure. We determined whether
      radiographic measurements and clinical characteristics are different between
      patients with and without tibial component failure to identify mechanisms of
      failure and strategies to reduce the risk. METHODS: Out of 3,212 primary TKAs
      (2,725 TKAs with a two-year minimum follow up), of which all were performed with
      KA, eight patients presented with tibial component failure. Radiographic
      measurements, clinical characteristics (e.g. age, gender, BMI, etc.), revision
      surgical records, and Oxford knee scores were compared to control cohort patients
      matched 1:3. RESULTS: Tibial component failure presented at an average of 28 +/-
      15 months after primary TKA. Patients with tibial component failure had a 6 kg/m2
      greater body mass index (p = 0.034) and 5 degrees  greater posterior slope of the
      tibia component (p = 0.002) than controls. Final follow-up averaged 56 +/- 19
      months after the primary TKA and 28 +/- 24 months after the revision TKA. The
      final Oxford knee score was 39 +/- 4.6 for patients with tibial component failure
      and 44 +/- 6.5 for the controls (p = 0.005). CONCLUSIONS: The incidence of tibial
      component failure after KA TKA was 0.3% and was caused by posterior subsidence or
      posterior edge wear and not varus subsidence. The strategy for lowering the risk
      of tibial component failure when performing KA is to set the tibial component
      parallel to the flexion-extension plane (slope) and varus-valgus plane of the
      native joint line.

PMID- 28493213
TI  - 3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for
      Bone Tissue Engineering Applications.
AB  - Millions of patients worldwide require bone grafts for treatment of large,
      critically sized bone defects from conditions such as trauma, cancer, and
      congenital defects. Tissue engineered (TE) bone grafts have the potential to
      provide a more effective treatment than current bone grafts since they would
      restore fully functional bone tissue in large defects. Most bone TE approaches
      involve a combination of stem cells with porous, biodegradable scaffolds that
      provide mechanical support and degrade gradually as bone tissue is regenerated by
      stem cells. 3D-printing is a key technique in bone TE that can be used to
      fabricate functionalized scaffolds with patient-specific geometry. Using 3D
      printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB)
      scaffolds can be produced to have the desired mechanical properties, geometry,
      and osteoinductivity needed for a TE bone graft. This book chapter will describe
      the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds.
      Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these
      scaffolds in vitro will be described to demonstrate the osteoinductivity of the
      scaffolds.

PMID- 28493214
TI  - Theoretical-Experimental Photophysical Investigations of the Solvent Effect on
      the Properties of Green- and Blue-Light-Emitting Quinoline Derivatives.
AB  - This paper describes the investigations on the solvatochromic effect and the
      photophysical properties of quinoline derivatives, compounds with potential
      applicability in optoelectronic devices. Using an experimental and theoretical
      approach, the effect of the solvent and the insertion of the phenyl, nitro, amino
      and dimethylamino group in the quinoline backbone were investigated. The use of
      Density Functional Theory (DFT) calculations provided the bases for the
      understanding of the energetic transitions observed in the absorption and
      fluorescence experiments. In general, it was observed a change in the wavelength
      of maximum absorption and fluorescence quantum yield of the studied compounds
      caused by the substituents in the quinoline core. This effect was correlated with
      the solvent dielectric constants.

PMID- 28493215
TI  - Cervical disc replacement surgery: indications, technique, and technical pearls.
AB  - PURPOSE OF REVIEW: Cervical disc replacement (CDR) is a surgical option for
      appropriately indicated patients, and high success rates have been reported in
      the literature. Complications and failures are often associated with patient
      indications or technical variables, and the goal of this review is to assist
      surgeons in understanding these factors. RECENT FINDINGS: Several investigations
      have been published in the last 5 years supporting the use of CDR in specific
      patient populations. CDR has been shown to be comparable or favorable to anterior
      cervical discectomy and fusion in several meta-analyses and mid-term follow-up
      studies. CDR was developed as a technique to preserve motion following a
      decompression procedure while minimizing several of the complications associated
      with fusion and posterior cervical spine procedures. Though success with cervical
      fusion and posterior foraminotomy has been well documented in the literature,
      high rates of mid- and long-term complications have been clearly established. CDR
      has also been associated with several complications and challenges with regard to
      surgical technique, though improvements in implant design have lead to an
      increase in utilization. Several devices currently exist and vary in terms of
      material, design, and outcomes. This review paper discusses indications, surgical
      technique, and technical pearls and reviews the CDR devices currently available.

PMID- 28493216
TI  - Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial
      Fibrillation in Older People: Results of an Evidence-Based Review and
      International Consensus Validation Process (OAC-FORTA 2016).
AB  - BACKGROUND: Age appropriateness of anticoagulants for stroke prevention in atrial
      fibrillation is uncertain. OBJECTIVE: To review oral anticoagulants for the
      treatment of atrial fibrillation in older (age >65 years) people and to classify
      appropriate and inappropriate drugs based on efficacy, safety and tolerability
      using the Fit-fOR-The-Aged (FORTA) classification. METHODS: We performed a
      structured comprehensive review of controlled clinical trials and summaries of
      individual product characteristics to assess study and total patient numbers,
      quality of major outcome data and data of geriatric relevance. The resulting
      evidence was discussed in a round table with an interdisciplinary panel of ten
      European experts. Decisions on age appropriateness were made using a Delphi
      process. RESULTS: For the eight drugs included, 380 citations were identified.
      The primary outcome results were reported in 32 clinical trials with explicit and
      relevant data on older people. Though over 24,000 patients aged >75/80 years were
      studied for warfarin, data on geriatric syndromes were rare (two studies
      reporting on frailty/falls/mental status) and missing for all other compounds.
      Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist
      oral anticoagulants (including low/high-intensity dabigatran and high-intensity
      edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon,
      acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting
      the absence of data. CONCLUSIONS: All non-vitamin K antagonist oral
      anticoagulants and warfarin were classified as beneficial or very beneficial in
      older persons (FORTA-A or -B), underlining the overall positive assessment of the
      risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally
      used in Europe, the lack of evidence should challenge current practice.

PMID- 28493217
TI  - What Is the Mid-term Failure Rate of Revision ACL Reconstruction? A Systematic
      Review.
AB  - BACKGROUND: When anterior cruciate ligament (ACL) reconstruction fails, a
      revision procedure may be performed to improve knee function, correct
      instability, and allow return to activities. The results of revision ACL
      reconstruction have been reported to produce good but inferior patient-reported
      and objective outcomes compared with primary ACL reconstruction, but the degree
      to which this is the case varies widely among published studies and may be
      influenced by heterogeneity of patients, techniques, and endpoints assessed. For
      those reasons, a systematic review may provide important insights.
      QUESTIONS/PURPOSES: In a systematic review, we asked: (1) What is the proportion
      of revision ACL reconstruction cumulative failures defined as rerupture or
      objective failure using prespecified clinical criteria at mean followup of at
      least 5 years? (2) What are the most common complications of revision ACL
      reconstruction? METHODS: A systematic review was performed by searching
      PubMed/Medline, EMBASE, and CENTRAL. We included studies that reported the
      clinical evaluation of revision ACL reconstruction with Lachman test, pivot shift
      test, side-to-side difference with KT-1000/2000 arthrometer, and with a mean
      followup of at least 5 years. We excluded studies that incompletely reported
      these outcomes, that reported only reruptures, or that were not in the English
      language. Extracted data included the number of graft reruptures and objective
      clinical failure, defined as a knee that met one of the following endpoints:
      Lachman test Grade II to III, pivot shift Grade II to III, KT-1000/2000 > 5-mm
      difference, or International Knee Documentation Committee Grade C or D. For each
      study, we determined the proportion of patients who had experienced a rupture of
      the revision ACL graft as well as the proportion of patients who met one or more
      of our clinical failure endpoints. Those proportions were summed for each study
      to generate a percentage of patients who met our definition of cumulative
      failure. Complications and reoperations were recorded but not pooled as a result
      of inconsistency of reporting and heterogeneity of populations across the
      included studies. Of the 663 screened studies, 15 articles were included in the
      systematic review. Because one study reported two separate groups of patients
      with different treatments, 16 case series were considered in the evaluation.
      RESULTS: The proportion of reruptures (range, 0%-25%) was > 5% in only four of 16
      series and > 10% in only one of them. The objective clinical failures (range, 0%
      82%) was > 5% in 15 of 16 series and > 10% in 12 of them. The proportion exceeded
      20% in five of 16 series. The cumulative failures (range, 0%-83%) was > 5% in all
      except one series and > 10% in 12 of 16 series; five series had a cumulative
      failure proportion > 20%. The most frequent complications were knee stiffness and
      anterior knee pain, whereas reoperations were primarily debridement and
      meniscectomies. CONCLUSIONS: Considering rerupture alone as a failure endpoint in
      patients who have undergone revision ACL reconstruction likely underestimates the
      real failure rate, because the percentage of failures noticeably increases when
      objective criteria are also considered. Whether patient-reported and subjective
      scores evaluating knee function, level of activity, satisfaction, and pain might
      also contribute to the definition of failure may be the focus of future studies.
      LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 28493218
TI  - Curriculum Overhaul in Psychiatric Residency: An Innovative Approach to Revising
      the Didactic Lecture Series.

PMID- 28493219
TI  - A critical appraisal of the cost effectiveness of laparoscopic colorectal surgery
      for oncological and non-oncological resections.
AB  - The aim of this study was to critically appraise the cost effectiveness of the
      laparoscopic colorectal (LCRS) surgery using published randomised, control trials
      (RCTs). Published RCTs comparing the cost effectiveness of LCRS with conventional
      open surgery were selected from the search of standard electronic databases and
      the extracted data were analysed using the statistical software RevMan 5.3. Seven
      RCTs on 2197 patients reported the cost effectiveness of the LCRS. There was
      significant heterogeneity (tau 2 = 161,772.25, chi 2 = 166.69, df = 6, p =
      0.00001, I 2 = 96%) among included randomised, controlled trials. In the random
      effects model analysis (MD 320.37, 95% CI -38.21, 678.95, z = 1.75, p < 0.08),
      the LCRS was costing L320.37 more than open colorectal resection but it failed to
      reach the statistical significance indicating that LCRS is as much cost effective
      as the open approach. LCRS is a cost effective intervention and should be offered
      routinely to all patients requiring colorectal resections provided the resources
      and expertise are available.

PMID- 28493220
TI  - Continuous intraoperative neural monitoring in thyroid surgery: a Mexican
      experience.
AB  - Intraoperative continuous neural monitoring (C-IONM) during thyroid surgery has
      been recognized as a useful tool to identify and confirm recurrent laryngeal
      nerve integrity. The aim of the present study is to analyze electromyographic
      features and thresholds for normal vocal fold function in our initial experience
      with C-IONM in thyroid surgery. C-IONM was utilized in 57 patients who underwent
      thyroid surgery between July 2012 and December 2015. EMG parameters were analyzed
      looking for potential predictors of postoperative vocal fold dismotility. There
      were 54 females (94.7%) and 3 males (5.3%) with a mean age of 46.7 +/- 11.6
      years. C-IONM was successfully registered in 89 of 107 nerves at risk (83.1%).
      Mean basal amplitude was 727.31 +/- 471.25 MUV and mean final amplitude was
      650.27 +/- 526.87 MUV (P = 0.095, CI 95% 13.83-167.91). Mean basal latency was
      5.23 +/- 1.42 mS and mean final latency was 5.18 +/- 1.50 mS (P = 0.594, CI 95%
      0.39-0.24). Four patients had transient postoperative vocal fold paresis. None of
      these four patients had loss of signal (LOS), three had transient decrease in
      amplitude, and one had a normal registry throughout the operation. C-IONM is a
      useful tool to identify patients in whom intraoperative RLN is at risk during
      surgery. Final amplitude above 500 MUV and no LOS is associated with RLN
      integrity and normal postoperative vocal fold function.

PMID- 28493222
TI  - [Twelve years of the S3 guideline Fibromyalgia Syndrome-a never-ending war?]

PMID- 28493221
TI  - Radical surgery for gastric cancer in octogenarian patients.
AB  - To valuate feasibility and results of radical surgery in octogenarian patients
      with gastric cancer. We collected data on 60 patients that underwent gastrectomy
      with an R0 resection at our Institution from 2010 to 2015. Patients were divided
      into two groups: octogenarian (OG) (n = 26), consisting of patients aged 80-89
      years, and younger (YG) (n = 34), consisting of patients under 80 years of age.
      All patients were treated with total or subtotal gastrectomy with
      lymphadenectomy. A D2-lymphadenectomy was performed in 11 and 24 patients, a D1+
      in 5 and 4, a D1 in 8 and 6, and a D0 in 2 and 0 cases in OG and YG respectively.
      The overall morbidity rate was 42.3% (11/26) in OG and 29.4% (10/34) in YG, while
      90-days mortality was observed in four (15.4%) and one (2.9%) patients in OG and
      YG, respectively. The median hospital stay was 9 days (2-31) and 9.5 days (6-66)
      in OG and YG, respectively. Gastrectomy with radical resection and limited
      lymphadenectomy should be recommended for octogenarian patients with good
      performance status and low co-morbidity.

PMID- 28493223
TI  - [Physiotherapy, occupational therapy and physical therapy in fibromyalgia
      syndrome : Updated guidelines 2017 and overview of systematic review articles].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n =8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      literature search for systematic reviews of randomized, controlled trials on
      physiotherapy, occupational therapy and physical therapy from December 2010 to
      May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus
      databases. Levels of evidence were assigned according to the classification
      system of the Oxford Centre for Evidence-Based Medicine version 2009. The
      strength of recommendations was achieved by multiple step formalized procedures
      to reach a consensus. Efficacy, risks, patient preferences and applicability of
      available therapies were weighed up against each other. The guidelines were
      reviewed and approved by the board of directors of the societies engaged in the
      development of the guidelines. RESULTS AND CONCLUSION: Low to moderate intensity
      endurance and strength training are strongly recommended. Chiropractic, laser
      therapy, magnetic field therapy, massage and transcranial magnetic stimulation
      are not recommended.

PMID- 28493224
TI  - [Psychotherapy and psychological procedures for fibromyalgia syndrome : Updated
      guidelines 2017 and overview of systematic review articles].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n =8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      systematic search of the literature for systematic reviews of randomized,
      controlled studies on psychological and psychotherapeutic procedures from
      December 2010 to May 2016 was performed in the Cochrane library, MEDLINE,
      PsycINFO and Scopus databases. Levels of evidence were assigned according to the
      classification system of the Oxford Centre for Evidence-Based Medicine version
      2009. The strength of recommendations was achieved by multiple step formalized
      procedures to reach a consensus. Efficacy, risks, patient preferences and
      applicability of available therapies were weighed up against each other. The
      guidelines were reviewed and approved by the board of directors of the societies
      engaged in the development of the guidelines. RESULTS AND CONCLUSION: Cognitive
      behavioral therapies received a strong recommendation but biofeedback, guided
      imagery and hypnosis received a weak recommendation.

PMID- 28493225
TI  - [Definition, diagnostics and therapy of chronic widespread pain and the (so
      called) fibromyalgia syndrome in children and adolescents : Updated guidelines
      2017].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n = 8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      search of the literature for case series (cross-sectional- and longitudinal
      studies) for the topics diagnosis, etiology and pathophysiology and for
      randomised controlled trials (RCT) for treatment modalities from December 2010 to
      May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus
      databases. Levels of evidence were assigned according to the classification
      system of the Oxford Centre for Evidence-Based Medicine version 2009. The
      strength of recommendations was achieved by multiple step formalized procedures
      to reach a consensus. Efficacy, risks, patient preferences and applicability of
      available therapies were weighed up against each other. The guidelines were
      reviewed and approved by the board of directors of the societies engaged in the
      development of the guidelines. RESULTS AND CONCLUSION: No consensus was achieved
      in the guideline group on whether the diagnostic label "juvenile fibromyalgia"
      should be used in the management of children and adolescents with chronic
      widespread pain. There was consensus in the guideline group that antidepressants
      and anticonvulsants should not be used to treat pain in the so-called juvenile
      fibromyalgia syndrome.

PMID- 28493227
TI  - [Complementary and alternative procedures for fibromyalgia syndrome : Updated
      guidelines 2017 and overview of systematic review articles].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n =8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      search of the literature for systematic reviews of randomized controlled trials
      of complementary and alternative therapies from December 2010 to May 2016 was
      performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels
      of evidence were assigned according to the classification system of the Oxford
      Centre for Evidence-Based Medicine version 2009. The strength of recommendations
      was formed by multiple step formalized procedures to reach a consensus. Efficacy,
      risks, patient preferences and applicability of available therapies were weighed
      up against each other. The guidelines were reviewed and approved by the board of
      directors of the societies engaged in the development of the guidelines. RESULTS
      AND CONCLUSION: Meditative movement therapies (e.g. qi gong, tai chi and yoga)
      are strongly recommended. Acupuncture and weight reduction in cases of obesity
      can be considered.

PMID- 28493226
TI  - [Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017,
      overview of systematic review articles and overview of studies on small fiber
      neuropathy in FMS subgroups].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was planned for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n =8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      systematic search of the literature from December 2010 to May 2016 was performed
      in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Prospective
      population-based studies and systematic reviews with meta-analyses of case
      control studies were taken into consideration for the statements. Levels of
      evidence were assigned according to the classification system of the Oxford
      Centre for Evidence-Based Medicine version 2009. The statements were generated by
      multiple step formalized procedures. The guidelines were reviewed and approved by
      the board of directors of the societies engaged in the development of the
      guidelines. RESULTS: Current data do not enable identification of distinct
      factors in the etiology and pathophysiology of fibromyalgia syndrome.
      Fibromyalgia syndrome can be associated with inflammatory rheumatic diseases,
      gene polymorphisms, life style factors (e.g. smoking, obesity and lack of
      physical activity), depressive disorders as well as physical and sexual abuse in
      childhood and adulthood. CONCLUSION: Fibromyalgia syndrome is most probably the
      end result of various pathogenetic factors and pathophysiological mechanisms.

PMID- 28493228
TI  - [Multimodal therapy of fibromyalgia syndrome : Updated guidelines 2017 and
      overview of systematic review articles].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n = 8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      search of the literature for systematic reviews on randomized controlled trials
      of multimodal therapy from December 2010 to May 2016 was performed in the
      Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were
      assigned according to the classification system of the Oxford Centre for Evidence
      Based Medicine version 2009. The strength of recommendations was achieved by
      multiple step formalized procedures to reach a consensus. Efficacy, risks,
      patient preferences and applicability of available therapies were weighed up
      against each other. The guidelines were reviewed and approved by the board of
      directors of the societies engaged in the development of the guidelines. RESULTS
      AND CONCLUSION: The use of multimodal therapy (combination of aerobic exercise
      with at least one psychological therapy) with a duration of at least 24 h is
      strongly recommended for patients with severe forms of fibromyalgia.

PMID- 28493229
TI  - [General treatment principles, coordination of care and patient education in
      fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review
      articles].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n =8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      search of the literature for systematic reviews on randomized, controlled trials
      on patient education and shared decision-making from December 2010 to May 2016
      was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases.
      Levels of evidence were assigned according to the classification system of the
      Oxford Centre for Evidence-Based Medicine version 2009. The strength of
      recommendations was achieved by multiple step formalized procedures to reach a
      consensus. Efficacy, risks, patient preferences, clinical and practical
      applicability of available therapies were weighed up against each other. The
      guidelines were reviewed and approved by the board of directors of the societies
      engaged in the development of the guidelines. RESULTS AND CONCLUSION: The
      diagnosis of fibromyalgia syndrome should be explicitly communicated to the
      affected individual. Shared decision-making with the patient on the therapeutic
      options based on individual preferences of the patient, comorbidities and the
      success of previous treatment is recommended. A step-wise treatment approach
      depending on the severity of fibromyalgia syndrome and the response to
      therapeutic measures is recommended.

PMID- 28493230
TI  - [Methodology report of the 2017 guidelines on fibromyalgia syndrome].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was planned for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n = 8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest.
      RESULTS: A systematic search of the literature from December 2010 to May 2016 was
      performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels
      of evidence were assigned according to the classification system of the Oxford
      Centre for Evidence-Based Medicine version 2009. The strength of recommendations
      was achieved by multiple step formalized procedures to reach a consensus.
      Efficacy, risks, patient preferences and applicability of therapies available
      were weighed up against each other. The guidelines were reviewed and approved by
      the board of directors of the societies engaged in the development of the
      guidelines. CONCLUSION: The guidelines are published in several forms, i.e.
      complete and short scientific versions and clinical practice and patient
      versions.

PMID- 28493231
TI  - [Drug therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of
      systematic review articles].
AB  - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
      number 145/004, was scheduled for April 2017. METHODS: The guidelines were
      developed by 13 scientific societies and 2 patient self-help organizations
      coordinated by the German Pain Society. Working groups (n =8) with a total of 42
      members were formed balanced with respect to gender, medical expertise, position
      in the medical or scientific hierarchy and potential conflicts of interest. A
      literature search for systematic reviews of randomized controlled drug trials
      from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE,
      PsycINFO and Scopus databases. Levels of evidence were assigned according to the
      classification system of the Oxford Centre for Evidence-Based Medicine version
      2009. The strength of recommendations was achieved by multiple step formalized
      procedures to reach a consensus. Efficacy, risks, patient preferences and
      applicability of available therapies were weighed up against each other. The
      guidelines were reviewed and approved by the board of directors of the societies
      engaged in the development of the guidelines. RESULTS AND CONCLUSION:
      Amitriptyline and duloxetine are recommended in the case of comorbid depressive
      disorders or generalized anxiety disorder and pregabalin in the case of
      generalized anxiety disorder. Off-label use of duloxetine and pregabalin can be
      considered if there are no comorbid mental disorders or no generalized anxiety
      disorder. Strong opioids are not recommended.

PMID- 28493232
TI  - Anthracycline induced cardiotoxicity: biomarkers and "Omics" technology in the
      era of patient specific care.
AB  - Anthracyclines are highly effective against a variety of malignancies. However,
      their dose-dependent cardiotoxic effects can potentially limit their use. In the
      past decade, serum biomarkers have been used to diagnose, monitor, predict, and
      prognosticate disease. Biomarkers such as cardiac troponin and natriuretic
      peptides have some predictive value, but still lack reliability in this patient
      population. Novel biomarkers such as galectin-3, soluble ST-2 proteins,
      myeloperoxidase, and fibrocytes are being explored as potential biomarkers to
      reliably predict the onset of cardiotoxicity. Leveraging multiomics technology to
      map highly sensitive biomarkers in an integrated approach through pattern
      deconvolution may better define those at highest risk of developing
      cardiotoxicity and further the goal of precision medicine. In this work, we aim
      to provide a brief overview of traditional serum biomarkers, summarize current
      investigations on novel circulating biomarkers, and discuss a systems-based
      approach to anthracycline-induced cardiotoxicity through "omics" technology.

PMID- 28493234
TI  - Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors.
AB  - Brain tumors are becoming a major cause of death. The classification of brain
      tumors has gone through restructuring with regard to some criteria such as the
      presence or absence of a specific genetic alteration in the 2016 central nervous
      system World Health Organization update. Two categories of genes with a leading
      role in tumorigenesis and cancer induction include tumor suppressor genes and
      oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms
      that result in their loss of function. As for the oncogenes, overexpression and
      amplification are the most common mechanisms of alteration. Important cell cycle
      genes such as p53, ATM, cyclin D2, and Rb have shown altered expression patterns
      in different brain tumors such as meningioma and astrocytoma. Some genes in
      signaling pathways have a role in brain tumorigenesis. These pathways include
      hedgehog, EGFR, Notch, hippo, MAPK, PI3K/Akt, and WNT signaling. It has been
      shown that telomere length in some brain tumor samples is shortened compared to
      that in normal cells. As the shortening of telomere length triggers chromosome
      instability early in brain tumors, it could lead to initiation of cancer. On the
      other hand, telomerase activity was positive in some brain tumors. It is
      suggestive that telomere length and telomerase activity are important diagnostic
      markers in brain tumors. This review focuses on brain tumors with regard to the
      status of oncogenes, tumor suppressors, cell cycle genes, and genes in signaling
      pathways as well as the role of telomere length and telomerase in brain tumors.

PMID- 28493233
TI  - Neurite Outgrowth Stimulated by Oxytocin Is Modulated by Inhibition of the
      Calcium Voltage-Gated Channels.
AB  - Neuropeptide oxytocin contributes to the regulation of the neuron differentiation
      and cell morphology. However, the precise mechanisms are not yet fully
      understood. Oxytocin receptor function and its coupling to calcium entry are
      obvious objects of interest in relation to the neuron morphology. Postsynaptic
      scaffolding proteins including SHANK proteins interact with other synaptic
      molecules and change dendritic morphology. SH-SY5Y neuroblastoma cell line
      represents a useful neurobiological in vitro model to study the short-term
      oxytocin effects on neurite outgrowth and underlying mechanisms. In the present
      study, we show that oxytocin induces an increase in the intracellular calcium in
      SH-SY5Y cells. Specificity of the calcium influx was verified by blockade of the
      oxytocin receptors with oxytocin receptor antagonist L-371,257. Neurite outgrowth
      stimulated by oxytocin was inhibited by specific voltage-gated calcium channel
      blockers. The exposure of SH-SY5Y cells to oxytocin resulted in a significant
      increase in the gene expression of SHANK1 and SHANK3 proteins. Overall, the
      present data indicate that oxytocin may contribute to the regulation of
      scaffolding proteins expression known to be associated with clusters of calcium
      channels at the cell membrane. It appears that oxytocin stimulated neurite
      outgrowth is, at least, in part dependent on the voltage-gated calcium channels.

PMID- 28493235
TI  - The Impact of Radiation and Its Timing on Donor Internal Mammary Vessel
      Histopathology at the Time of Autologous Microvascular Breast Reconstruction.

PMID- 28493236
TI  - Donor-Site Outcomes for the Osteocutaneous Radial Forearm Free Flap.

PMID- 28493237
TI  - Dedicated Barrett's surveillance sessions managed by trained endoscopists improve
      dysplasia detection rate.

PMID- 28493238
TI  - Cold polypectomy for duodenal adenomas: a prospective clinical trial.
AB  - Background and study aims Endoscopic resection is effective in treating
      nonampullary duodenal adenomas but has a high incidence of complications. Cold
      polypectomy, including cold forceps polypectomy (CFP) and cold snare polypectomy
      (CSP), is safe and effective in treating colorectal polyps. However, its utility
      in sporadic nonampullary duodenal adenomas has not been investigated. The purpose
      of this prospective study was to examine the safety and efficacy of cold
      polypectomy for sporadic nonampullary duodenal adenomas. Patients and methods
      Between March 2015 and June 2016, patients who were endoscopically diagnosed with
      sporadic nonampullary duodenal adenomas up to 6 mm underwent cold polypectomy.
      Patients with pathologically confirmed adenomas underwent endoscopic biopsy 3
      months after resection. The main outcomes of interest were incomplete resection
      and complications. Results Overall, 39 lesions in 30 patients were removed via
      cold polypectomy (CFP, 9 lesions in 8 patients; CSP, 30 lesions in 22 patients).
      Seven of 9 (77.8 %) and 29 of 30 (96.7 %) lesions were removed en bloc via CFP
      and CSP, respectively. Pathologically, 34 of the 39 lesions (87.2 %) were
      confirmed as adenomas, and their mean size was 3.9 +/- 1.2 mm (range 2 - 6 mm).
      Of the 34 adenomas, 20 (58.8 %) were R0 resection lesions, of which 3 of 9 (33.3
      %) and 17 of 25 (68.0 %) had undergone CFP and CSP, respectively. No delayed
      bleeding or intraprocedural/delayed perforation was observed. All 30 patients
      with the 34 pathologically confirmed adenomas underwent upper gastrointestinal
      endoscopy 3 months after cold polypectomy, and no morphological or pathological
      recurrence was identified. Conclusions In this small study, cold polypectomy
      appeared to be safe and effective in treating diminutive and small sporadic
      nonampullary duodenal adenomas.(Clinical trial registration number:
      UMIN000016829).

PMID- 28493239
TI  - Erratum: Noninvasive Ventilation in Newborns <= 1,500 g after Tracheal
      Extubation: Randomized Clinical Trial.

PMID- 28493240
TI  - Does Vitamin D Status Correlate with Cardiometabolic Risk Factors in Adults with
      Growth Hormone Deficiency?
AB  - Apart from being individually associated with cardiometabolic health, 25(OH)D and
      IGF-1 interplay with a positive correlation between them, which raises questions
      about the role of vitamin D for the adverse cardiovascular (CV) risk profile in
      hyposomatotropism. Thus, we aimed to investigate vitamin D status in GH
      deficiency (GHD) and the association between 25(OH)D and metabolic syndrome
      (MetS), its components, and other surrogate markers of CV risk. A total of 129
      GHD adults (childhood-onset GHD, 41.9%) underwent blood testing (glucose,
      insulin, lipid profile, uric acid); blood pressure, anthropometric and
      bioelectrical-impedance measurements. Other CV risk markers were examined in a
      subsample of the initial population - hsCRP, adiponectin, and asymmetric
      dimethylarginine (n=88); carotid intima-media thickness (n=44). Total serum
      25(OH)D, measured by electro-chemiluminescence binding assay, was used for
      vitamin D status assessment (adequate,>=30 ng/ml; insufficient, 20-29.9 ng/ml;
      deficient,<20 ng/ml). Data demonstrated high prevalence of hypovitaminosis D in
      GHD (deficiency 79.1%; insufficiency 14.7%), with lower 25(OH)D among adult-onset
      GHD subjects (14.0+/-7.2 vs. 16.8+/-8.0 ng/ml, p=0.039) and patients with MetS
      (11.8+/-4.5 vs. 16.3+/-8.1 ng/ml, p<0.0001). 25(OH)D correlated negatively and
      weakly with BMI, waist circumference, percent body fat, visceral fat area, and
      systolic BP. Regardless of whether vitamin D is a cause or a consequence of these
      metabolic abnormalities, 25(OH)D testing in hyposomatotropism is advisable.
      Normalization of vitamin D status is not proven to improve CV outcomes in general
      population, but it might have favorable effects in GHD, as its benefits might be
      restricted to patients with both low 25(OH)D and certain risk factors.

PMID- 28493241
TI  - [The Use of Jumbo Cups in Revision Total Hip Arthroplasty].
AB  - Extra-large uncemented jumbo cups are among the most common methods of acetabular
      revision. Jumbo cups do not contribute to bone stock restoration, and in the case
      of a subsequent revision, an even larger bone defect is to be expected. Thus,
      understanding long-term survival is essential. The present article discusses the
      literature relevant to this topic and addresses technical and implant-specific
      characteristics of jumbo cups. In summary, jumbo cups show an acceptable long
      term survival rate, with aseptic loosening as the most common reason for revision
      and dislocation being the most common complication. Through the development of
      alternative revision systems, jumbo cups have lost their importance in today's
      practice. However, they can serve as a benchmark for studies of newer
      technologies in revision total hip arthroplasty.

PMID- 28493242
TI  - [Current Status of Spine Surgery in Germany: Results of a Survey of Members of
      the German Spine Society].
AB  - Background Mono- (MSS) and bisegmental spinal fusion (BSS) are frequently
      performed surgical interventions in German hospitals. Despite the high number of
      cases, only few data on treatment procedures and concepts for pre-, peri-, and
      postoperative care are available. The aim of the survey was to gain detailed
      insights into treatment procedures and medical approaches in elective MSS and BSS
      care in Germany in order to extract recommendations for improving patient care.
      Materials and Methods Members of the German Spine Society (DWG) were sent a
      newsletter, inviting them to participate in a survey; 209 senior physicians
      agreed to do so. They were asked about length of stay (LOS), care concepts and
      outcome measurement. Results The data from 142 completed questionnaires were used
      in the analysis. In some aspects, there was a consistency in practice:
      preoperative patient information about the care process and discharge on the
      basis of qualitative criteria. However, there was also considerable variability
      in practice: in rehabilitation, restrictions, radiological control, pre- and
      postoperative outcome measurement and interdisciplinary coordination. Conclusion
      More than half of the surveyed physicians declared that they followed a
      structured care plan. However, the treatment procedures in MSS and BSS care are
      very heterogeneous in German hospitals. It also became clear that this is
      particularly pronounced in aspects of treatment for which evidence is lacking.
      The results give important indications regarding aspects of treatment procedures
      and organizational structures that can be optimized for better patient care.

PMID- 28493243
TI  - [Bridges from Psychosomatics to General Practice and Family Medicine].

PMID- 28493244
TI  - [German Translation of the COPD Self-Efficacy Scale: Development and Validation
      of a Short Form].
AB  - Illness-specific self-efficacy is important in the disease-management of patients
      with COPD (Chronic Obstructive Pulmonary Disease). Nevertheless, there is no
      instrument to measure the illness-specific self-efficacy in the German speaking
      countries. The purposes of the study were to translate the COPD Self-Efficacy
      Scale (CSES) into German (CSES-D) and to determine the psychometric criteria.
      Another objective was to construct a short form of the CSES-D. A total of 199
      participants with COPD were recruited. The factorial structure of the CSES
      including 5 dimensions could not be confirmed with exploratory and confirmatory
      factor analyses. However, the short form of the CSES-D indicated acceptable fit
      indices. The internal consistencies of the subscales psychological stress
      (alpha=0.95) and physical exertion (alpha=0.92) were good. The correlations
      between the CSES-Dkurz and convergent and discriminant questionnaires confirmed
      the validity of the instrument. The results indicate that the CSES-Dkurz is a
      valid and reliable instrument to assess illness-specific self-efficacy of COPD
      patients. Further, studies are needed to verify the factorial construct validity
      of the CSES-Dkurz.

PMID- 28493245
TI  - [The Prognostic Significance of ICF Data with Regard to Realization of
      Recommendations Given in the Medical Discharge Report after In-Patient
      Psychosomatic Rehabilitation].
AB  - Target In this trial, the prognostic significance of ICF-related diagnostics
      compared to social and medical, disease-related and personal factors with regard
      to realization of recommendations given in the medical discharge report after the
      in-patient psychosomatic rehabilitation should be examined. Methodology ICF
      related, social and medical, disease-related and personal prognostic factors were
      surveyed by questionnaires and interviews, on admission, discharge and 6 months
      after discharge from rehabilitation (time of catamnesis). As target criteria,
      realizations of recommendations from the fields of sports and exercise,
      psychotherapy and social medicine were chosen, they could be evaluated by
      telephone from N=344 participants at the time of catamnesis. For determination of
      relevant predictors, bivariate and multi-variate analyses were performed. Results
      70% of patients realized the recommended sports and exercise, 45% the recommended
      psychotherapy and 44% a social and medical recommendation. With regard to the
      target criterion for the realization of recommended sports and exercise, the
      elevated prognostic factors had only a low prognostic value. For the prognosis of
      the target criterion of realizing a recommended psychotherapy, interpersonal
      problems and a low ability to interact in groups (Mini-ICF-APP) turned out to be
      relevant ICF-related predictors. Different problems (e. g., job-related
      conditions) appeared as relevant, ICF-related predictors concerning the
      realization of social and medical recommendations. Disturbances of reliability,
      self-evaluated by means of ICF AT-50 Psych, showed in the bivariate analyses
      significant correlations with the target criteria. Conclusion Besides other
      variables, also ICF-supported attributes turned out to be suitable for the
      prognosis of target criteria. They should be evaluated and considered in the
      rehabilitation process.

PMID- 28493246
TI  - [Posttraumatic Growth after Profession-Related Traumatization in Rescue Workers].
AB  - This study aims to explore the association between self-reported secondary
      traumatization and personal growth in a sample of Belarusians rescue workers,
      focusing on the mediating role of 2 socio-interpersonal processes (disclosure and
      co-rumination). In a cross-sectional survey, self-reported posttraumatic growth
      and secondary traumatization were assessed in a sample of 168 rescue workers.
      Posttraumatic growth was positively linked to the extent of secondary
      traumatization, likewise disclosure and co-rumination were positively linked to
      posttraumatic growth. Mediation analyses revealed that the association between
      secondary traumatization and posttraumatic personal growth was mediated by
      disclosure and co-rumination. The results thus are in favor of a socio
      interpersonal perspective on posttraumatic adjustment.

PMID- 28493247
TI  - [The Systemic and the Subjective Perspective on Schizophrenia or how far Away are
      we from a Patient Centred Psychiatry?]

PMID- 28493248
TI  - [Editor's Comment].

PMID- 28493249
TI  - ?

PMID- 28493250
TI  - ?

PMID- 28493251
TI  - ?

PMID- 28493252
TI  - [Immunotherapy Against Head and Neck Cancer Stem Cells].
AB  - Immunotherapy against head and neck cancer stem cells Immunologic therapies like
      antibodies in solid tumors like squamous cell cancer of the head and neck are
      administered either alone or in combination with radiation and chemotherapy.
      Despite some respectable successes, the effect of this therapy reaches its limits
      due the ability of the tumor to escape the immune system. Cancer stem cells seem
      to play an important role in this process due to their intrinsic resistance to
      conventional therapy and the ability to regenerate tumor heterogeneity. This way
      they substantially contribute to the formation of recurrences and metastases.
      Therefore, future immunotherapies should target specifically this subpopulation,
      possibly in combination with other therapeutic modalities. In this review the
      immunologic features of cancer stem cells and their potential as target for
      immunotherapies is summarized.

PMID- 28493253
TI  - ?

PMID- 28493255
TI  - ?

PMID- 28493254
TI  - [Hearing Aid Fitting in Adults].
AB  - The identification and treatment of hearing disorders belong to the fundamental
      tasks of an ENT-specialist. In this context the fitting of hearing aids has a
      special relevance. To verify a highly qualified medical care the knowledge of the
      audiological threshold values for the indication of the fitting of hearing aids
      and the detection of early signs for impaired communication are essential. The
      current quality assurance agreement defines technical and steric conditions
      pertaining to hearing aid fitting in the context of statutory health insurance.
      Only after approval of these postulated requirements the attending physician is
      allowed to bring to account his effort. The current regulations on medical
      devices specify both the basic requirement for a medical prescription and the
      expenses for hearing aids that are covered by the healthy insurances. A qualified
      hearing aid fitting is only possible if the ENT-specialist not only prescribes
      the device, but also conscientiously checks the comparative adjustments made by
      the hearing aid acoustician. Beside the knowledge about the general mode of
      operation and the different types of hearing aids ENT-specialist should know
      audiological and anatomic limits for the fitting of hearing aids.

PMID- 28493256
TI  - ?

PMID- 28493257
TI  - Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and
      topoisomerase IIalpha) in borderline ovarian tumors: Correlation with
      clinicopathological features.
AB  - BACKGROUND: The expression of p53 has been studied not only in primary human
      ovarian carcinomas, but also in borderline ovarian tumors, however, the results
      were discordant. Expression patterns of proteins involved in cell proliferation
      and apoptosis have been investigated in various human neoplasms, including female
      genital tract neoplasms. OBJECTIVE: The aim of this investigation was to assess
      the staining pattern and immunolocalization of p53 and selected proliferative
      markers (Ki-67, MCM3, PCNA, and topoisomerase IIalpha) in borderline ovarian
      tumors (BOTs). DESIGN: The study group consisted of 42 women who underwent pelvic
      surgery between 2006-2015. The median patients' age was 46 years. The
      immunoperoxidase technique was employed using antibodies against p53, Ki-67,
      MCM3, PCNA, and topoisomerase IIalpha. RESULTS: For p53, nuclear expression was
      observed in BOTs, however, cytoplasmatic immunoreactivity was also detected.
      Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including
      overexpression found in 6 (14%). There were no significant differences in p53
      expression between subgroups of clinicopathological variables. Immunoexpression
      of Ki-67, MCM3, PCNA, and topoisomerase IIalpha was nuclear. Ki-67 expression was
      positive in 12 (29%) cases and there was a trend towards a relationship between
      patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher
      Ki-67 expression was found in tumors of >=10 cm in diameter compared to smaller
      tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA
      expression in 28 (67%), yet none of clinicopathological factors was related to
      them. Topoisomerase IIalpha expression was present in 14 (33%) cases and,
      interestingly, its significantly higher expression was observed in BOTs of >=10
      cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's
      correlation revealed highly significant positive associations between Ki-67 and
      topoisomerase IIalpha (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001).
      CONCLUSIONS: We report a high positive immunostaining rate for p53, suggesting a
      role of TP53 alterations in the development of BOTs in humans. The new finding of
      higher topoisomerase IIalpha immunostaining positivity in BOTs of >=10 cm may be
      clinically relevant and requires further studies on larger patient groups.

PMID- 28493258
TI  - A regional framework for action on substance use and public health.

PMID- 28493259
TI  - Situational analysis: regional review of the substance use Atlas 2015.
AB  - The Atlas project on substance use is a global WHO project that aims to collect
      and disseminate data on resources for the prevention and treatment of substance
      use disorders. Information on resources available in the WHO Eastern
      Mediterranean Region was first published in 2012. The Atlas questionnaire was
      updated in 2014 and data were collected in all WHO Member States. All countries
      of the Region submitted the Atlas questionnaire. This report presents the latest
      key information on resources for the prevention and treatment of substance use
      disorders in the Eastern Mediterranean Region based on the responses of the
      countries to the questionnaire. Current estimates show that the burden
      attributable to drug use disorders in the Region is high. Health system resources
      for the prevention and treatment of substance use disorders vary across
      countries, but are generally still insufficient to provide adequate care and
      treatment for people with these disorders. Countries need to strengthen
      prevention and treatment of substance use disorders, particularly by increasing
      coverage of treatment interventions.

PMID- 28493260
TI  - International drug control system and the United Nations General Assembly Special
      Session (UNGASS) on the world drug problem: an overview.
AB  - The international drug control system is one of the oldest consensus-based
      multilateral systems in existence. It provides the basis for the international
      community and the individual Member States to effectively put in place the
      mechanisms to address the problem of drug production trafficking and use of
      illicit substances at different levels. Currently, the international drug control
      conventions enjoy near universal adherence, with over 180 states party to the
      three international drug control conventions. This level of consensus is
      impressive given the highly contentious nature of the subject matter. Since the
      global drug situation remains very dynamic, the multilateral system has the
      ability to adjust and respond to the changing situation over the years. This
      report summarizes for healthcare managers those developments and their
      implications post UNGASS for the development of policies and in identifying the
      challenges and priorities for their responses to address the drug situation in
      order to achieve the targets set for 2019 and the 2030 agenda for sustainable
      development.

PMID- 28493261
TI  - Out-of-pocket cost of drug abuse consequences: results from Iranian National
      Mental Health Survey.
AB  - Drug abuse has significant cost to the individual, the family and the society.
      This study aimed to assess out of-pocket costs of consequences of drug use
      disorder. Data were drawn from the Iranian Mental Health Survey (IranMHS) through
      face-to-face interviews with 7841 respondents aged 15-64 years. We used a bottom
      up cost-ofillness method for economic analysis. Out-of-pocket costs for treatment
      of mental and drug problems, treatment of medical illnesses, as well as costs of
      crimes were assessed. The average of total annual expense was US$ 2120.6 for
      those with drug use disorder, which was 23.5% of annual income of an average
      Iranian family in the year 2011. The average of total out-of-pocket cost was US$
      674.6 for those with other mental disorder and US$ 421.9 for those with no mental
      disorder. Catastrophic payment was reported in 47.6% of the patients with drug
      use disorder and 14.4% of those with other mental disorder. Thus, considerable
      amount of family resources are spent on the consequences of drug use.

PMID- 28493262
TI  - Level of khat dependence, use patterns, and psychosocial correlates in Yemen: a
      cross-sectional investigation.
AB  - Chronic khat use is associated with negative health consequences. However, no
      study has fully characterized individuals who are khat dependent. This paper
      examines socio-demographic and psychosocial correlates of adult khat dependence.
      A total of 270 khat users (129 women) in Yemen completed face-to-face interviews
      and provided demographic information and data on patterns of khat use, subjective
      mood, and sleep quality. The Severity of Dependence Scale-Khat (SDS-khat) was
      used to assess level of khat dependence. A series of analysis of variance was
      conducted. Khat users, on average, used khat for 5.2 hours a day (SD = 2.3) for
      5.7 days a week (SD = 2.0). Individuals who screened positive for khat dependence
      reported longer duration of khat sessions per day, higher frequency of khat use
      per week, greater levels of negative mood and sleep disturbances, and were more
      likely to endorse physical symptoms after khat use (P < 0.05). Future research
      should elucidate mechanisms responsible for khat dependence symptomatology.

PMID- 28493263
TI  - Pattern of addiction and its relapse among habitual drug abusers in Lahore,
      Pakistan.
AB  - This study assessed the pattern of drug abuse and the reasons for relapse of
      addiction among male drug addicts seeking rehabilitative services in different
      centres in Lahore, Pakistan. A cross-sectional survey was conducted on male drug
      abusers from April to December 2016. Nonprobability purposive sampling was done
      to collect a sample of 119 participants. A structured questionnaire and in-depth
      interviews were used for data collection. Out of 119 participants, 71.4% were in
      the age group 15-35 years. Educational levels were low in the majority, with
      68.1% below secondary education. Unmarried (51.3%) and unemployed (44.5%)
      participants were at the greatest risk of using drugs. The age of addiction in
      45% of patients was < 18 years and 40% had been abusing substances for > 5 years.
      Reasons for starting drug abuse were recreation (37%), curiosity (34.5%), and
      lifechanging events (14.3%). Reasons for relapse included association with former
      addicts, negative reactions from family, inability to manage the craving and
      work/social stress.

PMID- 28493264
TI  - Drop-out from a drug treatment clinic and associated reasons.
AB  - The aim of this study was to assess drop-out rates and associated reasons among
      patients at the Iranian National Center for Addiction Studies (INCAS) clinic. In
      a one-year period (April 2014 to March 2015), all patients with drug dependence
      who had been referred for treatment and attended for a first assessment were
      included in this study (N=242). Those who received treatment were followed until
      March 2016. Survival analysis showed that 70.2% had dropped out from treatment.
      Log rank test showed that treatment drop-out rates differed between the different
      approaches used (P < 0.001), with the lowest slope inbuprenorphine maintenance
      treatment and the highest in the detoxification programme. Drop-out rates within
      the first three months was 62% (SE= 0.05) and 82.4% (SE=0.03) for opioids and
      stimulants dependence, respectively. Analyses were performed using SPSS (Version
      21.0) and STATA software, (version 13.0). From the patients' perspective,
      motivational inconsistencies were considered as the main reason for not starting
      or leaving treatment. The findings of this study could give service providers a
      better grasp of drop-out rates and the associated reasons.

PMID- 28493265
TI  - National Rehabilitation Center programme performance measures in the United Arab
      Emirates, 2013.
AB  - The aim of this study was to measure the performance of the National
      Rehabilitation Center (NRC) programme and the services it provides. A 6-point
      tool was developed based on international standards with appropriate performance
      measures. The elements of the tool were applied to the electronic data files for
      2013. The results showed that there were some operational, quality and data
      system issues. Some items were easily accessible, e.g. capacity, waiting time,
      family involvement. Others were difficult to sort and find and some were not
      available in the electronic system and had to be retrieved from other sources,
      e.g. programme effectiveness. There was a high no-show rate for appointments
      (46%) and readmission rate (52%) and most families did not attend family sessions
      (72%). This was a valuable exercise which identified gaps in operations and
      records. The findings were shared with the different teams to help improve the
      quality of data and services and the tool will be used for annual performance
      evaluations.

PMID- 28493266
TI  - Prevalence, determinants and impacts of khat chewing among professional drivers
      in Southwestern Saudi Arabia.
AB  - The objective of this study was to assess the prevalence and determinants of khat
      chewing, and explore its social, economic and work impacts and examine its
      relation with road traffic accidents (RTA) among professional drivers in Jazan
      region, Saudi Arabia. A cross-sectional study was conducted on 215 drivers
      recruited from transport stations in Jazan region by random cluster sampling. An
      interview questionnaire was utilized for data collection, and 47.4% of drivers
      were currently khat chewers. Using a logistic regression, the independent
      predictors of khat chewing were being a citizen of Saudi Arabia, divorced or
      widowed, working for less than 4 hours/day, and a non-seatbelt user. Khat chewing
      was significantly associated with shorter working hours; higher average number of
      significant RTA, and higher frequency of traffic violation. In conclusion, khat
      chewing habit affected almost half of the professional drivers in Jazan area.
      Moreover, khat chewing was associated with impaired working ability and
      productivity, family conflicts, and violation of traffic rules.

PMID- 28493267
TI  - Substance use prevention: evidence-based intervention.
AB  - The global substance use problem is a serious public health concern that affects
      not only health, safety and well-being of communities, but also social and
      economic development. It particularly affects children, young people and their
      families. All Member States should set substance use prevention measures and
      programmes as a priority in order to promote health and reduce social harm.
      During the past few decades there has been a significant advance in prevention
      science that has led to the development of international prevention standards and
      globally accepted evidence-based interventions. This review looks into the key
      requirements, components and strategic interventions needed for a public health
      approach to prevention of substance use and disorders, and its health and social
      consequences. It aims at supporting Member States and civil society to identify
      the key elements that support countries and local communities to increase the
      number of substance use protective approaches in relation to risk factors across
      all relevant domains.

PMID- 28493268
TI  - Development of services for substance use problems: need for a system-based
      approach.
AB  - This review describes systems-level innovations that may enhance accessibility,
      economy and integration of treatment services for substance-related disorders.
      After introducing a conceptual model to describe the resources, qualities and
      effectiveness of drug treatment services, evidence is reviewed in three areas
      (primary care, criminal justice, and mental health) that illustrate how systems
      level concepts can be used to organize services to maximize their population
      impact. Special attention is given to systems issues in relation to the
      development of services in countries of the Eastern Mediterranean Region.

PMID- 28493269
TI  - Interventions for the management of substance use disorders: an overview.
AB  - For the past 50 years, there has been a systematic effort to expand and improve
      treatment services for individuals with substance use disorders by developing an
      evidence base to guide practice. This policy brief aims to review the available
      interventions for the management of substance use disorders, examine the evidence
      base for these interventions, including the WHO Mental Health Gap Action
      Programme intervention guide, and make recommendations related to the treatment
      of substance use disorders. In the development of this policy brief, numerous
      documents were reviewed. The WHO Mental Health Gap Action Programme intervention
      guide offers the most well synthesized summary of interventions that have
      evidence of support, clinical acceptance, extensive implementation and expert
      consensus. The recommendations within this policy brief incorporate the core
      recommendations on substance use disorder elements included in the mhGAP
      intervention guide.

PMID- 28493270
TI  - Public health alternatives to incarceration for drug offenders.
AB  - Drug users are vastly overrepresented in prison populations. Once inside they
      face increased risks of acquiring infections such as HIV, hepatitis and TB, and
      on release they face an elevated risk of fatal overdose. Relapse and recidivism
      are the norm following release from prison. The implementation of evidence-based
      drug treatment programmes in prison is rare, yet drug treatment in prison reduces
      the transmission of infections, recidivism and fatal overdose on release.
      Recognising the negative returns associated with incarceration, many
      jurisdictions have begun to consider alternatives such as depenalisation of the
      personal use of illicit drugs, provision of treatment and social reintegration of
      drug offenders, and a shift in focus from supply reduction to demand and harm
      reduction measures in the community and in prison. Women with drug problems are
      twice as likely to have been imprisoned for a drug offence as incarcerated men.
      Similarly, HIV prevalence is higher among female inmates. Serious attention
      should be paid to implementation of non-custodial sentences for women,
      particularly during pregnancy and those with young children.

PMID- 28493271
TI  - Alcohol and substance use in humanitarian and postconflict situations.
AB  - A wide range of substance use problems are prevalent in a variety of humanitarian
      settings. The Inter Agency Standing Committee (IASC) guidelines on mental health
      and psychosocial support during emergencies highlights that during humanitarian
      and post conflict situations, substance use is associated with problems including
      gender-based violence, organized crime and the serious neglect of children.
      Although substance use is a public health issue in humanitarian settings it has
      always been a neglected area of public health with very limited information
      available in both published and grey literature on this matter. This review
      presents an overview of the problem and existing assessment and interventions
      tools to address substance use in conflict and post-conflict situations.

PMID- 28493272
TI  - Khat use and related addiction, mental health and physical disorders: the need to
      address a growing risk.
AB  - Khat use is a drug problem characteristic of the Eastern Mediterranean Region,
      which is a widespread culturally accepted practice in some countries and is
      becoming more prevalent in others. Although limited use may not be accompanied by
      serious consequences, prolonged exposure could lead to dependence, psychosis and
      other psychiatric disorders and physical conditions such as hypertension,
      cardiovascular complications, sexual dysfunction, hepatoxicity and reduced birth
      weight of infants born to khat-chewing mothers. The widespread use and its burden
      on health and economy has raised concerns in the Region, although the extent of
      the problem is not well assessed. Additionally, most countries do not have a
      clear policy and plan with regard to khat use, and therefore there is hardly any
      structured prevention and treatment plan in place to respond to the problem. This
      review presents a picture of the extent of the problem, elaborates on related
      existing research initiatives and international treaties, policies and health
      service provisions, and outlines best policy and programme interventions in khat
      use countries.

PMID- 28493273
TI  - Use of amphetamine-type stimulants in the Islamic Republic of Iran, 2004-2015: a
      review.
AB  - Amphetamine-type stimulants (ATS) are the second most commonly used illicit drugs
      in the world, after cannabis. The production of ATS has increased worldwide,
      including in the Middle East. This review aims to assess ATS use in the Islamic
      Republic of Iran. PubMed, Scientific Information Database (a national database)
      and Iranian Center for Addiction Studies were searched. The review included
      studies on the general population, university and high school students, other
      specific populations, and drug users. The result show that self-reported
      methamphetamine and ecstasy use in 2016 was < 1% in the general population and
      university and high-school students, but the prevalence was higher in certain
      groups. There has also been an increase in the proportion of ATS users among
      clients of drug treatment centres. The findings highlight the need for high
      quality epidemiological studies and closer monitoring of stimulant use in
      different populations.

PMID- 28493274
TI  - Developing an interministerial substance use response strategy for Lebanon:
      process, content and lessons learned.
AB  - Evidence on substance use in Lebanon shows an increase in usage, limited
      availability and accessibility to evidence-based services, and high level of
      stigma and discrimination. In line with the "Mental Health and Substance Use
      Strategy for Lebanon 2015-2020", the Ministry of Public Health initiated the
      process of developing a strategy focused on substance use response to address
      these challenges in collaboration with the Ministries of Education and Higher
      Education, Interior and Municipalities, Justice and Social Affairs. The result of
      this process was a strategy launched jointly by the ministries including six
      domains of action covering the whole spectrum of substance use response with
      strategic objectives addressing the challenges identified through stakeholders'
      consultations. The following key principles adopted throughout the process
      contributed to the successful development of the strategy: building on evidence
      and international frameworks, maximizing the participation of all stakeholders,
      prioritising national consensus, maintaining flexibility and maximizing
      transparency.

PMID- 28493275
TI  - Focus issue | Bioartificial organs and tissue engineering.

PMID- 28493276
TI  - Analytical Characterization of the Hydrolysis of Barley Malt Macromolecules
      During Enzymatic Degradation Over Time Using AF4/MALS/RI.
AB  - The changes on the molecular weight distribution (MWD) and particle size
      distribution (PSD) during hydrolysis of barley malt in isothermal mashing
      procedures were determined using asymmetrical flow field flow fractionation
      coupled to multiangle laser light scattering and refractive index (AF4/MALS/RI).
      Mash/trials were focused on amylolytic starch degradation. Therefore,
      temperatures (65, 70, and 75  degrees C) were selected according to alpha- and
      beta-amylases range of activity. Samples were produced by triplicate, tracking
      amylolytic processes over time periods from 10 to 90 min in each mash/trial.
      AF4/MALS/RI analysis demonstrated significant differences on the values of the
      MWD and PSD according to the temperature/time profile used. At mashing times over
      30 min at a temperature of 65  degrees C, when alpha- and beta-amylase are both
      active, the decrease over time of the MWD and PSD was significantly higher (P <
      0.005) than at 70  degrees C when mainly alpha-amylase is active. At 75  degrees
      C, also the activity of alpha-amylase decreased and the MWD and PSD were
      significantly lower (P < 0.005) than at 70 or 65  degrees C at any time of the
      procedure. The MWD and PSD of beer components influence beer palate fullness,
      thus AF4/ MALS/RI would be a powerful tool for breweries to adapt their
      technological processes to obtain beers with particular sensorial attributes.

PMID- 28493277
TI  - Bone mineral density in complete androgen insensitivity syndrome and the timing
      of gonadectomy.
AB  - OBJECTIVE: Low bone mineral density (BMD) has been reported in complete androgen
      insensitivity syndrome (CAIS), but the impact of timing of gonadectomy is not
      known. We aimed to assess the relationship between age of gonadectomy and BMD in
      women with CAIS. DESIGN: Retrospective analysis of pre- and post-gonadectomy
      parameters in women with CAIS attending an adult Disorders of Sex Development
      (DSD) clinic in a tertiary centre. PATIENTS: One hundred and thirteen women with
      CAIS. MEASUREMENTS: Dual-energy X-ray absorptiometry (DXA) before and after
      gonadectomy; and pre-gonadectomy hormone profile. RESULTS: Mean BMD was reduced
      (95% confidence interval); T-score -1.34 (-1.55 to -1.13; P<.001) at the lumbar
      spine and -0.3 (-0.49 to -0.12; P=.001) at the hip. There was no relationship
      between age of gonadectomy and BMD. Thirty-two subjects had BMD measured before
      or within 2 years of gonadectomy, and mean BMD was reduced (95% CI) at the lumbar
      spine; T-score: -1.05 (-1.54 to -0.57; P<.001), but was normal at the hip; T
      score -0.04 (-0.35 to 0.28; P=.8). There was no relationship between BMD and
      history of hernia, testosterone, oestradiol or follicle stimulating hormone
      levels. Twelve subjects had DXA both before and after gonadectomy, and after 4.3
      (1.7-12.8) years, there was no change in BMD. CONCLUSIONS: We found reduced BMD
      at the spine and hip in subjects with CAIS. We found no relationship between age
      of gonadectomy and BMD, and we also found no drop in BMD in subjects followed up
      after gonadectomy.

PMID- 28493278
TI  - The bicellular tensile force sorts the localization of LSRs in bicellular and
      tricellular junctions.
AB  - Lipolysis-stimulated lipoprotein receptors (LSRs) localize to tricellular tight
      junctions. Recent studies have shown that changes in the localization and
      expression profiles of LSRs are associated with malignancy of endometrial
      carcinomas, although the precise mechanisms by which malignant progression
      induces changes in the localization of LSRs are still unknown. In this study, we
      found that changes in cell tension correlated with alterations in the junctional
      localization of LSRs in endometrial cancer Sawano cells. At high cell densities,
      myosin phosphatase target subunit 1 (MYPT1) localized to bicellular junctions,
      whereas activated myosin regulatory light chain 2 (MRLC2) was dislocated from
      these regions, suggesting that circumferential tensile forces decreased at high
      cell densities. Under these conditions, LSRs localized to tricellular junctions.
      In contrast, a phosphorylated form of MRLC2 localized to bicellular regions,
      while MYPT1 was excluded from these regions, suggesting that tensile forces
      formed along the circumferential edge at low cell densities. It is noteworthy
      that, when cells were cultured under these conditions, LSRs localized to
      bicellular regions. Upon treatment with a myosin inhibitor, LSR localization in
      bicellular junctions decreased at low cell densities. Overall, our results
      indicate that the modulation of cellular tension was involved in the
      translocation of LSRs from bicellular to tricellular tight junctions.

PMID- 28493279
TI  - Specific detection of GII-1 lineage of infectious bronchitis virus.
AB  - : Infectious bronchitis virus (IBV) is a worldwide prevalent RNA virus that
      causes highly contagious and economically devastating disease in chicken. The
      virus exists in many different genetic forms which made the disease control very
      difficult. The present study describes the development and validation of TaqMan
      probe-based real-time reverse transcription-polymerase chain reaction (real-time
      RT-PCR) targeting the S1 coding region of S gene characteristic for the GII-1
      lineage (formerly the D1466-like variant) of IBV. These strains are quite
      different from other European IBV belonging to different lineages of the GI
      genotype. The developed method was 30-fold more sensitive than used so far for
      standard nested RT-PCR with detection limit of 56 RNA copies per reaction. The
      specificity of the assay was also evaluated with a panel of different poultry
      pathogens. Repeatability and reproducibility of the method was very high with
      coefficients of variation lower than 4%. One hundred and twenty-seven IBV
      positive samples were tested by this method and GII-1 strains were detected in
      four of them (3.15%) which indicate a decrease in the GII-1 IBV prevalence in
      Poland. The assay was proven to be a valuable tool for rapid diagnosis of GII-1
      lineage of IBV strains and moreover it enabled the monitoring of viral loads
      which can be used to assess disease progression. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study reports a TaqMan probe-based real-time reverse transcription
      polymerase chain reaction (real-time RT-PCR) for rapid and accurate
      identification of GII-1 lineage (formerly D1466-like variant) of infectious
      bronchitis virus (IBV). The assay revealed to be more sensitive than standard
      nested RT-PCR assay, previously used for this purpose. The developed assay has
      been tested on numerous field samples and revealed 3.15% prevalence of this
      lineage of IBV in Polish chicken population. Moreover, this new assay enables the
      assessment of viral load measurement which might be useful for epidemiology and
      pathogenesis studies.

PMID- 28493280
TI  - Aquifers Shared Between Mexico and the United States: Management Perspectives and
      Their Transboundary Nature.
AB  - Totally 36 aquifers have been identified along the Mexico-U.S. border. Of these,
      only 16 have adequate data to provide a reasonable level of confidence to
      categorize them as transboundary. Limited and/or contrasting data over the other
      aquifers in the region reflects the void in transboundary groundwater management
      and assessment mechanisms throughout much of the Mexico-U.S. border. This paper
      identifies management mechanisms, structures, and institutional prioritization
      related to transboundary aquifers shared between Mexico and the United States. It
      also evaluates the differences in the transboundary nature of these aquifers, and
      how their combined hydrological and geographical considerations interrelate with
      local and regional social, economic, political, and even scale dimensions to
      create complex management challenges.

PMID- 28493281
TI  - Editorial: Being a mental health nurse.

PMID- 28493282
TI  - The importance of relationships: Care planning and care coordination in mental
      health.

PMID- 28493283
TI  - The Current Status of Research on the Integration of Sexual and Reproductive
      Health and HIV Services.
AB  - Integration of services for sexual and reproductive health (SRH) and HIV has been
      widely promoted globally in the belief that both clients and health providers
      benefit through improvements in quality, efficient use of resources, and lower
      costs, helping to maximize limited health resources and provide comprehensive
      client-centered care. This article builds on the growing body of research on
      integrated sexual SRH and HIV services. It brings together critical reviews on
      issues within the wider SRH and rights agenda and synthesizes recent research on
      integrated services, drawing on the Integra Initiative and other major research.
      Unintended pregnancy and HIV are intrinsically interrelated SRH issues, however
      broadening the constellation of services, scaling up, and mainstreaming
      integration continue to be challenging. Overcoming stigma, reducing gender-based
      violence, and meeting key populations' SRH needs are critical. Health systems
      research using SRH as the entry point for integrated services and interaction
      with communities and clients is needed to realize universal health coverage.

PMID- 28493284
TI  - Prognostic value of preoperative anti-thyroglobulin antibody in differentiated
      thyroid cancer.
AB  - CONTEXT: The coexistence of differentiated thyroid cancer (DTC) and thyroid
      autoimmune disease could represent a better or worse prognosis. This study
      investigated the prognostic importance of preoperative anti-thyroglobulin
      antibody (TgAb) in DTC patients. DESIGN AND PATIENTS: This retrospective hospital
      cohort study enrolled 1171 consecutive DTC patients with preoperative TgAb data,
      who underwent total thyroidectomy between January 2006 and December 2011.
      Clinical parameters studied included demographics, primary tumour
      characteristics, radioiodine therapy, thyroid function tests, preoperative
      thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. RESULTS: A
      total of 254 (21.7%) patients were preoperatively TgAb positive. The percentage
      positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was
      significantly higher in the TgAb-positive group. The TgAb-positive group had a
      significantly higher rate of lymphatic invasion and lymph node metastasis both
      overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group).
      The mean number of total and central lymph nodes dissected and rate of lateral
      lymph node dissection were significantly higher in the TgAb-positive group, both
      overall and in non-HT patients. In regression analysis, preoperative TgAb was an
      independent risk factor for lateral lymph node metastasis. Over 50.2+/-14.5
      months of follow-up, disease persistence/recurrence was not significantly
      different between patients with and without TgAb, both overall and in non-HT
      patients. Preoperative TgAb showed no significant correlation with final disease
      status. CONCLUSION: Positive preoperative serum TgAb is associated with worse
      primary tumour characteristics but rarely showed poor prognosis, probably due to
      more aggressive treatment of these subjects.

PMID- 28493285
TI  - Hidden floral adaptation to nocturnal moths in an apparently bee-pollinated
      flower, Adenophora triphylla var. japonica (Campanulaceae).
AB  - The discrepancy between observed flower visitors and those predicted based on
      floral phenotype has often cast doubt on the pollination syndrome concept. Here
      we show that this paradox may be alleviated by gaining better knowledge of the
      contributions of different flower visitors to pollination and the effects of
      floral traits that cannot be readily perceived by humans in Adenophora triphylla
      var. japonica. The blue, bell-shaped and pendant flowers of A. triphylla appear
      to fit a bee pollination syndrome. In contrast to this expectation, recent
      studies show that these flowers are frequented by nocturnal moths. We compared
      the flower visitor fauna, their visitation frequency and their relative
      contributions to seed set between day and night in two field populations of A.
      triphylla in Japan. We also determined the floral traits associated with temporal
      changes in the visitor assemblage, i.e. the timing of anthesis, the timing of
      changes in the sexual phase and the diel pattern of nectar production. While A.
      triphylla flowers were visited by both diurnal and nocturnal insects, the results
      from pollination experiments demonstrate that their primary pollinators are
      nocturnal settling-moths. Moreover, the flowers opened just after sunset, changed
      from staminate to pistillate phase in successive evenings and produced nectar
      only during the night, which all conform to the activity of nocturnal/crepuscular
      moths. Our study illustrates that the tradition of stereotyping the pollinators
      of a flower based on its appearance can be misleading and that it should be
      improved with empirical evidence of pollination performance and sufficient trait
      matching.

PMID- 28493286
TI  - Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and
      mortality in Canada reveals changing trends and geographic clustering for this
      malignancy.
AB  - BACKGROUND: Previous reports of geographic clustering of cutaneous T-cell
      lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of
      CTCL in married couples and family members raise a possibility of the existence
      of an external and potentially preventable trigger(s) for this rare skin cancer.
      METHODS: The authors studied CTCL incidence and mortality in Canada using 3
      distinct population-based cancer databases. Data on patients' sex, age at the
      time of diagnosis, subtype of CTCL malignancy, reporting province, city, and
      postal code were analyzed. CTCL cases were mapped across Canada using geographic
      information systems software. RESULTS: In total, 6685 patients with CTCL were
      identified in Canada during 1992 through 2010 (CTCL incidence rate, 11.32 cases
      per million individuals per year), of which 58% were males. The mean age at
      diagnosis was 59.4 +/- 21.5 years. Geographic analysis of patients revealed
      increased CTCL incidence on the provincial and city levels in several eastern
      provinces and in Manitoba. An analysis according to postal codes (Forward
      Sortation Area [FSA]) identified select communities in which several high
      incidence FSAs were contiguous or adjacent. Several of these FSAs were located in
      industrial regions of Canadian cities. Conversely, 3 of 8 low-incidence FSAs were
      clustered in Ottawa, Ontario, which has very little industrial presence. An
      analysis of CTCL mortality in Canada corroborated the current incidence findings.
      CONCLUSIONS: The current results provide a comprehensive analysis of CTCL burden
      in Canada and highlight several important areas of geographic case clustering.
      These findings argue that industrial exposures may play an important role in
      promoting CTCL pathogenesis. Cancer 2017;123:3550-67. (c) 2017 American Cancer
      Society.

PMID- 28493287
TI  - Soft tissue sarcoma nomograms and their incorporation into practice.
AB  - The accurate prediction of prognosis in patients with soft tissue sarcoma (STS)
      is a challenging issue. Extreme variability in the clinical and pathological
      characteristics of this family of tumors hinders the simple stratification of
      patients into meaningful prognostic cohorts. Precision medicine tools for the
      prediction of prognosis, such as nomograms, enable personalized computation of
      outcome based on clinical and pathological characteristics of both patient and
      tumor. The eighth edition of the American Joint Committee on Cancer staging
      manual moved from a "population-based" to a "personalized" approach endorsing
      high-quality nomograms to improve clinician prediction ability in definite
      patient subgroups. The first nomogram for STS was published in 2002, and this was
      followed by several prognostic predictors offered to clinicians. Focusing on a
      specific STS subgroup or site, nomograms can take into consideration highly
      specific factors relevant only in that particular scenario, thereby maximizing
      prognostic ability. The objective of this review was to critically evaluate
      available nomograms for patients with STS to provide clinicians and researchers
      with a choice of the most optimal tool for each specific patient. Cancer
      2017;123:2802-20. (c) 2017 American Cancer Society.

PMID- 28493288
TI  - Outcomes for patients with locally advanced pancreatic adenocarcinoma treated
      with stereotactic body radiation therapy versus conventionally fractionated
      radiation.
AB  - BACKGROUND: As systemic therapy has improved for locally advanced pancreatic
      cancer (LAPC), efforts to improve local control with optimal radiotherapy may be
      critical. Although conventionally fractionated radiation therapy (CFRT) has more
      recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT)
      is an emerging approach with promising results. With no studies to date comparing
      SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to
      evaluate these 2 modalities. METHODS: With the NCDB, patients with American Joint
      Committee on Cancer cT2-4/N0-1/M0 adenocarcinoma of the pancreas diagnosed from
      2004 to 2013 were analyzed. Radiation therapy delivered at <=2 Gy was deemed
      CFRT, and radiation therapy delivered at >=4 Gy per fraction was considered SBRT.
      Kaplan-Meier analysis, log-rank testing, and multivariate Cox proportional
      hazards regression were performed with overall survival (OS) as the primary
      outcome. Propensity score matching was used. RESULTS: Among 8450 patients, 7819
      (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. Receipt of SBRT
      was associated with superior OS in the multivariate analysis (hazard ratio, 0.84;
      95% confidence interval, 0.75-0.93; P < .001). With propensity score matching,
      988 patients in all were matched, with 494 patients in each cohort. Within the
      propensity-matched cohorts, the median OS (13.9 vs 11.6 months) and the 2-year OS
      rate (21.7% vs 16.5%) were significantly higher with SBRT versus CFRT (P =
      .0014). CONCLUSIONS: In this retrospective review using a large national
      database, SBRT was associated with superior OS in comparison with CFRT for LAPC,
      and these findings remained significant in a propensity-matched analysis. Further
      prospective studies investigating these hypothesis-generating results are
      warranted. Cancer 2017;123:3486-93. (c) 2017 American Cancer Society.

PMID- 28493290
TI  - Circulating thyroid cancer biomarkers: Current limitations and future prospects.
AB  - Differentiated thyroid cancer (DTC) is the most common malignancy of the
      endocrine system. There has been a significant increase in its incidence over the
      past two decades attributable mainly to the use of more sensitive diagnostic
      modalities. Ultrasound-guided fine needle aspiration cytology is the mainstay of
      diagnosis of benign disorders and malignancy. However, approximately 20% of
      lesions cannot be adequately categorized as benign or malignant. In the
      postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed
      for the detection of disease recurrence. Unfortunately, Tg antibodies are common
      and interfere with Tg measurement in this subset of patients. Despite this
      limitation, Tg remains the sole widely used thyroid cancer biomarker in the
      clinical setting. In an attempt to bypass antibody interference, research has
      focused mainly on mRNA targets thought to be exclusively expressed in thyroid
      cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been
      extensively studied both for discerning between benign disease and malignancy and
      in postoperative disease surveillance. However, results among reports have been
      inconsistent probably reflecting considerable differences in methodology.
      Recently, microRNA (miRNA) targets are being investigated as potential biomarkers
      in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable
      as mRNA during manipulation. Initial results have been encouraging but large
      scale studies are warranted to verify and elucidate their potential application
      in diagnosis and postoperative surveillance of thyroid cancer. Several other
      novel targets, primarily mutations and circulating cells, are currently emerging
      as promising thyroid cancer circulating biomarkers. Although interesting and
      intriguing, data are limited and derive from small-scale studies in specific
      patient cohorts. Further research findings demonstrating their value are awaited
      with anticipation.

PMID- 28493291
TI  - Prevalence of primary aldosteronism among patients with type 2 diabetes.
AB  - CONTEXT: Diabetes and hypertension coexist in 40%-60% of individuals with type 2
      diabetes. The coexistence of these two conditions is associated with increased
      risk of retinopathy, nephropathy and cardiovascular disease. OBJECTIVE: To
      investigate the prevalence of primary aldosteronism (PA) in a general cohort of
      persons with type 2 diabetes. DESIGN: Cross-sectional study involving six
      diabetes outpatient clinics in Sweden. PATIENTS: were enrolled individuals with
      type 2 diabetes between February 2008 and December 2013. MEASUREMENTS: Plasma
      aldosterone concentrations (PAC pmol/L) and direct renin concentrations (DRC
      mIU/L) were measured. Patients with increased aldosterone renin ratios (ARR) >65
      were further evaluated for PA. RESULTS: Of 578 consecutively screened patients
      with type 2 diabetes, 27 were treated with mineralocorticoid receptor antagonists
      (MRA) and potassium-sparing diuretics not further evaluated. Among the remaining
      551 patients, 38 had increased ARR, including 22 who were clinically indicated
      for PA tests and 16 who were not further evaluated due to severe comorbidities
      and old age. There were five (0.93%) patients with confirmed PA after
      computerized tomography and adrenal venous sampling. Patients with PA had higher
      systolic blood pressure (P=.032) and lower potassium levels (P=.027) than those
      without PA. No significant association was found between plasma aldosterone and
      diabetic complications. CONCLUSIONS: The prevalence of PA in an unselected cohort
      of patients with type 2 diabetes is relatively low, and measures of plasma
      aldosterone are not strong risk factors for micro- and macrovascular diabetic
      complications.

PMID- 28493292
TI  - Organocatalytic Stereoconvergent Synthesis of alpha-CF3 Amides:
      Triketopiperazines and Their Heterocyclic Metamorphosis.
AB  - The highly enantioselective alkylation of alpha-CF3 enolates, generated from
      triketopiperazines, has been accomplished through use of a bifunctional thiourea
      organocatalyst to facilitate 1,4-addition to varied enone acceptors. On treatment
      with appropriate nitrogen nucleophiles, the chiral triketopiperazine products
      undergo a metamorphosis, to provide novel fused heterocyclic lactams such as
      extended pyrazolopyrimidines.

PMID- 28493289
TI  - Intestinal epithelial claudins: expression and regulation in homeostasis and
      inflammation.
AB  - The intestinal epithelium forms a highly dynamic and selective barrier that
      controls absorption of fluid and solutes while restricting pathogen access to
      underlying tissues. Barrier properties are achieved by intercellular junctions
      that include an apical tight junction (TJ) and subjacent adherens junctions and
      desmosomes. The TJ tetraspan claudin proteins form pores between epithelial cells
      to control paracellular fluid and ion movement. In addition to regulation of
      barrier function, claudin family members control epithelial homeostasis and are
      expressed in a spatiotemporal manner in the intestinal crypt-luminal axis. This
      delicate balance of physiologic differential claudin protein expression is
      altered during mucosal inflammation. Inflammatory mediators influence
      transcriptional regulation, as well as endocytic trafficking, targeting, and
      retention of claudins in the TJ. Increased expression of intestinal epithelial
      claudin-1, -2, and -18 with downregulation of claudin-3, -4, -5, -7, -8, and -12
      has been observed in intestinal inflammatory disorders. Such changes in claudin
      proteins modify the epithelial barrier function in addition to influencing
      epithelial and mucosal homeostasis. An improved understanding of the regulatory
      mechanisms that control epithelial claudin proteins will provide strategies to
      strengthen the epithelial barrier function and restore mucosal homeostasis in
      inflammatory disorders.

PMID- 28493293
TI  - Responsiveness to oral prednisolone in severe asthma is related to the degree of
      eosinophilic airway inflammation.
AB  - BACKGROUND: Patients with severe asthma appear relatively corticosteroid
      resistant. Corticosteroid responsiveness is closely related to the degree of
      eosinophilic airway inflammation. The extent to which eosinophilic airway
      inflammation in severe asthma responds to treatment with systemic corticosteroids
      is not clear. OBJECTIVE: To relate the physiological and inflammatory response to
      systemic corticosteroids in asthma to disease severity and the baseline extent of
      eosinophilic inflammation. METHODS: Patients with mild/moderate and severe asthma
      were investigated before and after 2 weeks of oral prednisolone (Clintrials.gov
      NCT00331058 and NCT00327197). We pooled the results from two studies with common
      protocols. The US study contained two independent centres and the UK one
      independent centre. The effect of oral corticosteroids on FEV1 , Pc20, airway
      inflammation and serum cytokines was investigated. Baseline measurements were
      compared with healthy subjects. RESULTS: Thirty-two mild/moderate asthmatics, 50
      severe asthmatics and 35 healthy subjects took part. At baseline, both groups of
      asthmatics had a lower FEV1 and Pc20 and increased eosinophilic inflammation
      compared to healthy subjects. The severe group had a lower FEV1 and more
      eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone
      caused a similar degree of suppression of eosinophilic inflammation in all
      compartments in both groups of asthmatics. There were small improvements in FEV1
      and Pc20 for both mild/ moderate and severe asthmatics with a correlation between
      the baseline eosinophilic inflammation and the change in FEV1 . There was a ~50%
      reduction in the serum concentration of CXCL10 (IP-10), CCL22 (MDC), CCL17
      (TARC), CCL-2 (MCP-1) and CCL-13 (MCP-4) in both asthma groups after oral
      corticosteroids. CONCLUSIONS AND CLINICAL RELEVANCE: Disease severity does not
      influence the response to systemic corticosteroids. The study does not therefore
      support the concept that severe asthma is associated with corticosteroid
      resistance. Only baseline eosinophilic inflammation was associated with the
      physiological response to corticosteroids, confirming the importance of measuring
      eosinophilic inflammation to guide corticosteroid use.

PMID- 28493294
TI  - Commercial Mineral Enhanced Dairy By-Products as Sodium Replacers, Antioxidants
      and Calcium Fortifiers in Sausages.
AB  - Sausages are perceived as high in Na and with a too high Na:K ratio. Frankfurter
      type sausages are regarded as important contributors of sodium in the diet and
      thereby of health risks. Surplus products from the dairy industry are various
      mineral powders enriched in either potassium, calcium, or phosphate and include
      various amounts of lactose. Sausages were produced at 3 sodium levels (equivalent
      to 13, 15, and 17 g NaCl/kg sausage) using 4 different milk ingredients (a dried
      skimmed milk powder, a calcium enriched milk powder, a potassium enriched powder,
      and a lactose enriched powder). The sausages with added calcium and potassium
      enriched milk powders resulted in the hardest sausages when compared at the same
      sodium level. Milk mineral addition also produced whiter and less red sausages.
      No effect on rancidity after 6 wk at chill (4  degrees C) storage was observed by
      adding milk minerals, when compared with adding dried skimmed milk powder. A
      significant advantage of using these milk minerals in sausages is that the Na:K
      ratio can be reduced from an unhealthy (in this study 36) to a far healthier
      ratio (  2) with limited or no taste changes. High additions of milk calcium (6
      g/kg), where Ca-phosphates prevail, added as milk mineral, had no influence on
      sensory bitterness or aftertaste as typically observed for CaCl2 additions. Ca
      additions to sausages are presently presumed to be an advantage with respect to
      human nutrition.

PMID- 28493297
TI  - The error analysis of Lobular and segmental division of right liver by volume
      measurement.
AB  - The aim of this study is to explore the inconsistencies between right liver
      volume as measured by imaging and the actual anatomical appearance of the right
      lobe. Five healthy donated livers were studied. The liver slices were obtained
      with hepatic segments multicolor-infused through the portal vein. In the slices,
      the lobes were divided by two methods: radiological landmarks and real anatomical
      boundaries. The areas of the right anterior lobe (RAL) and right posterior lobe
      (RPL) on each slice were measured using Photoshop CS5 and AutoCAD, and the
      volumes of the two lobes were calculated. There was no statistically significant
      difference between the volumes of the RAL or RPL as measured by the radiological
      landmarks (RL) and anatomical boundaries (AB) methods. However, the curves of the
      square error value of the RAL and RPL measured using CT showed that the three
      lowest points were at the cranial, intermediate, and caudal levels. The U- or V
      shaped curves of the square error rate of the RAL and RPL revealed that the
      lowest value is at the intermediate level and the highest at the cranial and
      caudal levels. On CT images, less accurate landmarks were used to divide the RAL
      and RPL at the cranial and caudal layers. The measured volumes of hepatic
      segments VIII and VI would be less than their true values, and the measured
      volumes of hepatic segments VII and V would be greater than their true values,
      according to radiological landmarks. Clin. Anat. 30:585-590, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28493295
TI  - Towards ultrasound-guided adaptive radiotherapy for cervical cancer: Evaluation
      of Elekta's semiautomated uterine segmentation method on 3D ultrasound images.
AB  - PURPOSE: 3D ultrasound (US) images of the uterus may be used to adapt
      radiotherapy (RT) for cervical cancer patients based on changes in daily anatomy.
      This requires accurate on-line segmentation of the uterus. The aim of this work
      was to assess the accuracy of Elekta's "Assisted Gyne Segmentation" (AGS)
      algorithm in semi-automatically segmenting the uterus on 3D transabdominal
      ultrasound images by comparison with manual contours. MATERIALS & METHODS: Nine
      patients receiving RT for cervical cancer were imaged with the 3D Clarity(r)
      transabdominal probe at RT planning, and 1 to 7 times during treatment. Image
      quality was rated from unusable (0)-excellent (3). Four experts segmented the
      uterus (defined as the uterine body and cervix) manually and using AGS on images
      with a ranking > 0. Pairwise analysis between manual contours was evaluated to
      determine interobserver variability. The accuracy of the AGS method was assessed
      by measuring its agreement with manual contours via pairwise analysis. RESULTS:
      35/44 images acquired (79.5%) received a ranking > 0. For the manual contour
      variation, the median [interquartile range (IQR)] distance between centroids (DC)
      was 5.41 [5.0] mm, the Dice similarity coefficient (DSC) was 0.78 [0.11], the
      mean surface-to-surface distance (MSSD) was 3.20 [1.8] mm, and the uniform margin
      of 95% (UM95) was 4.04 [5.8] mm. There was no correlation between image quality
      and manual contour agreement. AGS failed to give a result in 19.3% of cases. For
      the remaining cases, the level of agreement between AGS contours and manual
      contours depended on image quality. There were no significant differences between
      the AGS segmentations and the manual segmentations on the images that received a
      quality rating of 3. However, the AGS algorithm had significantly worse agreement
      with manual contours on images with quality ratings of 1 and 2 compared with the
      corresponding interobserver manual variation. The overall median [IQR] DC, DSC,
      MSSD, and UM95 between AGS and manual contours was 5.48 [5.45] mm, 0.77 [0.14],
      3.62 [2.7] mm, and 5.19 [8.1] mm, respectively. CONCLUSIONS: The AGS tool was
      able to represent uterine shape of cervical cancer patients in agreement with
      manual contouring in cases where the image quality was excellent, but not in
      cases where image quality was degraded by common artifacts such as shadowing and
      signal attenuation. The AGS tool should be used with caution for adaptive RT
      purposes, as it is not reliable in accurately segmenting the uterus on 'good' or
      'poor' quality images. The interobserver agreement between manual contours of the
      uterus drawn on 3D US was consistent with results of similar studies performed on
      CT and MRI images.

PMID- 28493299
TI  - China's Transboundary Groundwater Cooperation in the Context of Emerging
      Transboundary Aquifer Law.
AB  - China shares more than 20 transboundary aquifers with its coaquifer states, but
      they have not exploited their transboundary groundwater resources, and these
      resources have not been governed by any international agreements. Given the close
      interaction between surface water and groundwater, and the growing demands for
      transboundary groundwater in China and its coaquifer states, there is increasing
      necessity for these countries to undertake international cooperation on this
      issue. This article overviews China's transboundary aquifers, reviews the duty to
      cooperate on China's transboundary groundwater as well as the emerging
      transboundary aquifer law. It concludes by providing some proposals on
      international cooperation in this context, based on the two theories of
      international water law-limited territorial sovereignty and common interests,
      taking into account the practicability of China's cooperation with its coaquifer
      states. The author suggests that China cooperates with its coaquifer states
      through such means as the exchange of data and information, joint monitoring, the
      conclusion of bilateral or multilateral aquifer agreements, the establishment of
      joint management mechanisms, and international technical cooperation.

PMID- 28493298
TI  - Organizing pneumonia as an extraintestinal manifestation of Crohn's disease in a
      child.
AB  - Crohn's disease (CD) is a chronic inflammatory disorder with an unknown etiology
      that commonly involves the gastrointestinal tract, and bronchopulmonary
      manifestations only occur in 0.4% of cases. There have not been any reports about
      pulmonary involvement in pediatric CD patients. We experienced a 14-year-old boy
      with Crohn's disease diagnosed with organizing pneumonia by chest CT-guided
      biopsy examination. His pneumonia was intractable despite the administration of
      multiple antibiotics, and steroid therapy was very effective. In pediatric
      patients with CD whose lung disease does not respond to antibiotics, OP should be
      considered as a possible diagnosis.

PMID- 28493300
TI  - Timing of surgery for placenta previa with suspected abnormally invasive
      placentation: a test of team competency?

PMID- 28493301
TI  - The implementation of the Care Programme Approach for service users with a
      learning disability. Building Bridges to the same Old Horizons?
AB  - : WHAT IS KNOWN ON THE SUBJECT?: People with mental health problems and learning
      disabilities often do not receive the care they require. The Care Programme
      Approach (CPA) is meant to help with this. However, there have been many problems
      in the past with the introduction of the CPA into mental health services. There
      is no literature which explores what factors help or hinder the introduction of
      the CPA for service users with a mental health and learning disability,
      especially from the perspective of those responsible for overseeing this process.
      WHAT DOES THIS ARTICLE ADD TO EXISTING KNOWLEDGE?: The implementation of the CPA
      for this service user group is fragmented, and services are not working together
      in partnership. The CPA is being effectively implemented for people who are
      deemed to present with a risk to themselves or others. If a service user does not
      present with a high risk, they are not provided care through the CPA. Service
      users were not involved in the development or introduction of the policy in
      practice. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Services need to work better
      at engaging service users when they are developing and introducing new policies.
      Rather than applying the CPA for all service users, across all services, it
      should only be considered for those deemed to present with a high risk. It is
      effectively implemented for these people. For those not deemed to present with a
      high risk, services should consider using alternative service user led care
      planning frameworks. ABSTRACT: Introduction The Care Programme Approach was
      introduced in England to ensure services met the needs of people with mental
      health problems and a concurrent learning disability (dual diagnosis). The CPA
      implementation was patchy and services failed to work in partnership. Aim This
      study aimed to explore the factors shaping the recent implementation of the CPA
      for service users with a dual diagnosis. Method A single case study approach was
      undertaken. Data were collected through interview (n = 26), documentary analysis
      (n = 64), steering group observation (n = 3) and the Partnership Assessment Tool
      (n = 26). Data were analysed using the Framework Approach. Results The CPA was
      only effectively implemented for people who were deemed to present with a high
      level of risk. Discussion The problems associated with implementation in the
      1990s continue more recently for those with a dual diagnosis. The CPA has become
      more aligned with risk management protocols than supporting individual service
      user's recovery. Implications for practice Service users should be involved in
      the implementation of policies which have an impact on their recovery. The CPA
      should only be applied for those who present with high-risk issues, whilst
      alternative user-led initiatives should be considered for other service users.

PMID- 28493302
TI  - Instrumental variables estimation of exposure effects on a time-to-event endpoint
      using structural cumulative survival models.
AB  - The use of instrumental variables for estimating the effect of an exposure on an
      outcome is popular in econometrics, and increasingly so in epidemiology. This
      increasing popularity may be attributed to the natural occurrence of instrumental
      variables in observational studies that incorporate elements of randomization,
      either by design or by nature (e.g., random inheritance of genes). Instrumental
      variables estimation of exposure effects is well established for continuous
      outcomes and to some extent for binary outcomes. It is, however, largely lacking
      for time-to-event outcomes because of complications due to censoring and
      survivorship bias. In this article, we make a novel proposal under a class of
      structural cumulative survival models which parameterize time-varying effects of
      a point exposure directly on the scale of the survival function; these models are
      essentially equivalent with a semi-parametric variant of the instrumental
      variables additive hazards model. We propose a class of recursive instrumental
      variable estimators for these exposure effects, and derive their large sample
      properties along with inferential tools. We examine the performance of the
      proposed method in simulation studies and illustrate it in a Mendelian
      randomization study to evaluate the effect of diabetes on mortality using data
      from the Health and Retirement Study. We further use the proposed method to
      investigate potential benefit from breast cancer screening on subsequent breast
      cancer mortality based on the HIP-study.

PMID- 28493303
TI  - Comprehensive profiling of rhizome-associated alternative splicing and
      alternative polyadenylation in moso bamboo (Phyllostachys edulis).
AB  - Moso bamboo (Phyllostachys edulis) represents one of the fastest-spreading plants
      in the world, due in part to its well-developed rhizome system. However, the post
      transcriptional mechanism for the development of the rhizome system in bamboo has
      not been comprehensively studied. We therefore used a combination of single
      molecule long-read sequencing technology and polyadenylation site sequencing (PAS
      seq) to re-annotate the bamboo genome, and identify genome-wide alternative
      splicing (AS) and alternative polyadenylation (APA) in the rhizome system. In
      total, 145 522 mapped full-length non-chimeric (FLNC) reads were analyzed,
      resulting in the correction of 2241 mis-annotated genes and the identification of
      8091 previously unannotated loci. Notably, more than 42 280 distinct splicing
      isoforms were derived from 128 667 intron-containing full-length FLNC reads,
      including a large number of AS events associated with rhizome systems. In
      addition, we characterized 25 069 polyadenylation sites from 11 450 genes, 6311
      of which have APA sites. Further analysis of intronic polyadenylation revealed
      that LTR/Gypsy and LTR/Copia were two major transposable elements within the
      intronic polyadenylation region. Furthermore, this study provided a quantitative
      atlas of poly(A) usage. Several hundred differential poly(A) sites in the rhizome
      root system were identified. Taken together, these results suggest that post
      transcriptional regulation may potentially have a vital role in the underground
      rhizome-root system.

PMID- 28493304
TI  - CPAM type 2-derived mesenchymal stem cells: Malignancy risk study in a 14-month
      old boy.
AB  - INTRODUCTION: The association between congenital pulmonary airway malformations
      (CPAM) and malignancy is reported in the literature. Interactions between the
      tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as
      crucial for understanding tumorigenesis. We characterized MSCs isolated from CPAM
      lesions in order to define potential malignancy risks. METHODS: CPAM II pulmonary
      tissue was used for MSC expansion; a "healthy" lung section from the same child
      was used as a comparator. Morphology, immunophenotype, differentiation and
      immunological capacity, proliferative growth, gene signature telomerase activity,
      and in vivo tumorigenicity in nude mice were evaluated. RESULTS: MSCs were
      successfully isolated and propagated from CPAM tissue. CPAM-MSCs presented the
      typical MSC morphology and phenotype, while exhibiting high proliferative
      capacity, reaching confluence at a median time of 5 days as well as
      differentiation capabilities. CPAM-MSCs at early passages were not neoplastic and
      chromosomally normal, even though unbalanced chromosomal rearrangements were
      noted by molecular karyotype. CONCLUSIONS: CPAM-MSCs exhibited specific features
      similar to tumor derived MSCs. Whilst there was no evidence of malignant
      transformation in the cystic tissue, our results provide evidence that this
      abnormal tissue has malignant potential. MSCs are considered important players in
      the tumor microenvironment and they have been closely linked to regulation of
      tumor survival, growth, and progression. Thus, early lesion resection also in
      asymptomatic patients might be indicated to exclude that the microenvironment may
      be potentially permissive to cancer development.

PMID- 28493305
TI  - Editorial.

PMID- 28493306
TI  - Decisions on Hydraulic Fracturing Must Be Science-Based.

PMID- 28493307
TI  - Hepatitis B virus screening and reactivation and management of patients with
      nasopharyngeal carcinoma: A large-scale, big-data intelligence platform-based
      analysis from an endemic area.
AB  - BACKGROUND: Chemotherapy, target therapy, and immunotherapy are increasingly
      being used in the systematic treatment of nasopharyngeal carcinoma (NPC), during
      which the occurrence of hepatitis B virus (HBV) reactivation might increase.
      However, data regarding HBV screening and reactivation and the clinical
      management of NPC patients with HBV infections are lacking. This study was aimed
      at clarifying the risk of reactivation for NPC patients on different regimens
      while providing evidence concerning HBV screening and management in an endemic
      area. METHODS: With the NPC database from an established big-data intelligence
      platform at Sun Yat-Sen University Cancer Center in China, NPC patients who were
      diagnosed between 2008 and 2016 and underwent HBV screening and regular
      monitoring of liver enzymes and HBV deoxyribonucleic acid (DNA) were analyzed.
      RESULTS: Among the 46,919 patients identified, the HBV screening rate was 24.8%
      (11,616 of 46,919). Among the screened patients with an HBV infection, regular
      monitoring of liver enzymes and HBV DNA occurred for 563 patients. The incidence
      of HBV reactivation and HBV-related hepatitis was 9.1% (51 of 563) and 2.5% (14
      of 563), respectively. The reactivation risk varied for different treatments and
      regimens and ranged from 0.0% to 21.4%. Detectable baseline HBV DNA (odds ratio
      [OR], 2.93; P < .01), the presence of liver metastasis at diagnosis (OR, 7.19; P
      < .01), and antiviral prophylaxis (OR, 0.29; P < .01) were significantly
      associated with reactivation. CONCLUSIONS: In NPC patients with chronic HBV
      infections on high-risk regimens, the reactivation risk is similar to or exceeds
      the risk associated with other immunosuppressive therapies for which screening
      and prophylaxis are recommended. Our findings, therefore, support HBV screening
      and prophylaxis for these patients, whereas regular monitoring might be
      appropriate for patients with resolved HBV infections or those receiving low-risk
      regimens. Cancer 2017;123:3540-9. (c) 2017 American Cancer Society.

PMID- 28493308
TI  - North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of
      pharmacogenetic-based dosing of irinotecan, oxaliplatin, and capecitabine as
      first-line therapy for patients with advanced small bowel adenocarcinoma.
AB  - BACKGROUND: Oxaliplatin in combination with either 5-fluorouracil or capecitabine
      is commonly used as first-line therapy for patients with small bowel
      adenocarcinoma. The addition of irinotecan improves survival in other
      gastrointestinal tumors but at the cost of hematologic toxicity. The authors
      performed a phase 2 cooperative group study (North Central Cancer Treatment Group
      N0543, Alliance) using genotype-dosed capecitabine, irinotecan, and oxaliplatin
      (gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1
      member A1 (UGT1A1) genotype to test: 1) whether the addition of irinotecan would
      improve outcomes; and 2) whether UGT1A1 genotype-based dosing could optimize
      tolerability. METHODS: Previously untreated patients with advanced small bowel
      adenocarcinoma received irinotecan (day 1), oxaliplatin (day 1), and capecitabine
      (days 2-15) in a 21-day cycle and were dosed with gCAPIRINOX according to
      UGT1A1*28 genotypes (6/6, 6/7, and 7/7). RESULTS: A total of 33 patients (17 with
      the 6/6 genotype, 10 with the 6/7 genotype, and 6 with the 7/7 genotype) were
      enrolled from October 2007 to November 2013; 73% were male, with a mean age of 64
      years (range, 41-77 years). Location of the primary tumor included the duodenum
      (58%), jejunum (30%), and ileum (9%). The regimen yielded a confirmed response
      rate of 37.5% (95% confidence interval, 21%-56%), with a median progression-free
      survival of 8.9 months and a median overall survival of 13.4 months. Neither
      hematologic toxicity (grade >=3 in 52.9%, 30.0%, and 33.3%, respectively, of the
      6/6, 6/7, and 7/7 genotype groups) nor tumor response rate (41.2%, 33%, and 33%,
      respectively) were found to differ significantly by UGT1A1 genotype. CONCLUSIONS:
      UGT1A1 genotype-directed dosing (gCAPIRINOX) appears to be feasible with
      favorable rates of hematologic toxicity compared with prior 3-drug studies in
      unselected patients. Larger studies would be needed to determine the regimen's
      comparability to oxaliplatin and capecitabine (CapeOx) alone or if
      response/toxicity differs among patients with different UGT1A1 genotypes. Cancer
      2017;123:3494-501. (c) 2017 American Cancer Society.

PMID- 28493309
TI  - Effect of Nanoemulsified and Microencapsulated Mexican Oregano (Lippia graveolens
      Kunth) Essential Oil Coatings on Quality of Fresh Pork Meat.
AB  - Fresh meat is a highly perishable food. This work aimed to evaluate the influence
      of Mexican oregano (Lippia graveolens Kunth) incorporated into active coatings
      (ACs) spread on fresh pork meat as free (FEO), nanoemulsified (NEO), and
      microencapsulated (MEO) essential oil (EO), on its microbiological,
      physicochemical and sensory properties during 15 d at 4 +/- 1  degrees C. Thymol
      and gamma-terpinene were identified in the EO. In vitro effect of 2.85 mg EO/cm2
      was tested against Brochothrix thermosphacta, Micrococcus luteus, Lactobacillus
      plantarum, Pseudomonas fragi, and Salmonella Infantis. FEO antioxidant capacity
      (DPPH assay) was significantly higher than that of thymol, NEO and MEO (93.53%,
      89.92%, 77.79%, and 78.50% inhibition, respectively), and similar to BHA (96.03%)
      and gallic acid (95.57%). FEO, NEO, and MEO ACs on meat caused growth inhibition
      of lactic acid bacteria (5 log population reduction) and Pseudomonas spp. (4 log
      reduction), whereas <=1.5 log population reduction was observed for B.
      thermosphacta and Salmonella Infantis. Meat microbiota was more efficiently
      controlled by MEO than by FEO or NEO. ACs delayed lipid and oxymyoglobin
      oxidation of fresh pork meat. After 15 d of cold storage meat added with EO
      coatings was desirable for panelists, whereas untreated (UT) samples were
      undesirable. Active coatings are a significant alternative method for fresh meat
      preservation.

PMID- 28493310
TI  - Evolution of Heterogeneous Mixed Siliciclastic/Carbonate Aquifers Containing
      Metastable Sediments.
AB  - Mixed carbonate and siliciclastic marine sediments commonly become freshwater
      aquifers in eastern coastal regions of the United States and many other global
      locations. As these deposits age, the carbonate fraction of the sediment is
      commonly removed by dissolution and the aquifer can become a solely siliciclastic
      system or contain zones or beds of pure quartz sand. During aquifer evolution,
      the sediment grain size characteristics, hydraulic conductivity, and porosity
      change. An investigation of these changes using mixed carbonate/siliciclastic
      sediment samples collected from a modern barrier island beach in southern Florida
      showed that the average mean grain diameter decreased with removal of the
      carbonate fraction, but the average hydraulic conductivity and porosity increased
      slightly, but not to statistical significance. This counterintuitive result
      occurs because of the change in the pore types from a combined shelter and
      intergranular pore system producing a dual porosity system in the mixed sediments
      to a single intergranular pore system in the siliciclastic sediment fraction.
      Within the mixed carbonate/siliciclastic sediment, in the pure carbonate
      fraction, large shell fractions form grain-supported large pores, which become
      filled with sand-sized quartz as the shell fragments decrease in size or as the
      sediment becomes compacted. The hydraulic conductivity increases because the
      shell fragments that were oriented perpendicular to flow caused an increase in
      the length of the flow path, or a larger scale tortuosity, compared with the flow
      through pure quartz sand.

PMID- 28493311
TI  - ETHQV6.3 is involved in melon climacteric fruit ripening and is encoded by a NAC
      domain transcription factor.
AB  - Fruit ripening is divided into climacteric and non-climacteric types depending on
      the presence or absence of a transient rise in respiration rate and the
      production of autocatalytic ethylene. Melon is ideal for the study of fruit
      ripening, as both climacteric and non-climacteric varieties exist. Two
      introgressions of the non-climacteric accession PI 161375, encompassed in the
      QTLs ETHQB3.5 and ETHQV6.3, into the non-climacteric 'Piel de Sapo' background
      are able to induce climacteric ripening independently. We report that the gene
      underlying ETHQV6.3 is MELO3C016540 (CmNAC-NOR), encoding a NAC (NAM, ATAF1,2,
      CUC2) transcription factor that is closely related to the tomato NOR (non
      ripening) gene. CmNAC-NOR was functionally validated through the identification
      of two TILLING lines carrying non-synonymous mutations in the conserved NAC
      domain region. In an otherwise highly climacteric genetic background, both
      mutations provoked a significant delay in the onset of fruit ripening and in the
      biosynthesis of ethylene. The PI 161375 allele of ETHQV6.3 is similar to that of
      climacteric lines of the cantalupensis type and, when introgressed into the non
      climacteric 'Piel de Sapo', partially restores its climacteric ripening capacity.
      CmNAC-NOR is expressed in fruit flesh of both climacteric and non-climacteric
      lines, suggesting that the causal mutation may not be acting at the
      transcriptional level. The use of a comparative genetic approach in a species
      with both climacteric and non-climacteric ripening is a powerful strategy to
      dissect the complex mechanisms regulating the onset of fruit ripening.

PMID- 28493313
TI  - The EPR Spectrum of Triplet Mesitylphosphinidene: Reassignment and New
      Assignment.
AB  - Low-temperature UV-photolysis of mesitylphosphiranes under highly anaerobic
      conditions leads to the formation of the triplet mesitylphosphinidene (MesP). The
      recorded X-band EPR spectrum of triplet MesP and the derived zero-field splitting
      parameter D=4.116 cm-1 differ significantly from those reported previously for
      this intermediate. New magnetic parameters of mesitylphosphinidene are discussed
      along with the results of DFT calculations.

PMID- 28493312
TI  - Minor allergen patterns in birch pollen allergen products-A question of pollen?
AB  - BACKGROUND: Contrary to the scientific differentiation between major and minor
      allergens, the regulatory framework controlling allergen products in the EU
      distinguishes relevant and non-relevant allergens. Given the lack of knowledge on
      their clinical relevance, minor allergens are usually not controlled by allergen
      product specifications. Especially, in birch pollen (BP) allergen products, minor
      allergens are commonly disregarded. OBJECTIVES: To quantify three minor allergens
      in BP allergen products from different manufacturers and to assess the influence
      of the utilized BP on minor allergen patterns. METHODS: Apart from common quality
      parameters such as Bet v 1 content, Bet v 4, Bet v 6 and Bet v 7 were quantified
      in 70 BP allergen product batches from six manufacturers, using ELISA systems
      developed in-house. Batch-to-batch variability was checked for agreement with a
      variability margin of 50%-200% from mean of the given batches for individual
      allergen content. Subsequently, minor allergen patterns were generated via
      multidimensional scaling and related to information on the pollen lots used in
      production of the respective product batches. RESULTS: Like the already
      established Bet v 4 ELISA, the ELISA systems for quantification of Bet v 6 and
      Bet v 7 were successfully validated. Differences in minor allergen content
      between products and batch-to-batch consistency were observed. Correlations
      between minor and major allergen content were low to moderate. About 20% of
      batches exceeded the variability margin for at least one minor allergen.
      Interestingly, these fluctuations could not in all cases be linked to the use of
      certain BP lots. CONCLUSIONS AND CLINICAL RELEVANCE: The impact of the observed
      minor allergen variability on safety and efficacy of BP allergen products can
      currently not be estimated. As the described differences could only in few cases
      be related to the used pollen lots, it is evident that additional factors
      influence minor allergens in BP allergen products.

PMID- 28493314
TI  - Use of LC-HRMS in full scan-XIC mode for multi-analyte urine drug testing - a
      step towards a 'black-box' solution?
AB  - The influx of new psychoactive substances (NPS) has created a need for improved
      methods for drug testing in toxicology laboratories. The aim of this work was to
      design, validate and apply a multi-analyte liquid chromatography-high-resolution
      mass spectrometry (LC-HRMS) method for screening of 148 target analytes belonging
      to the NPS class, plant alkaloids and new psychoactive therapeutic drugs. The
      analytical method used a fivefold dilution of urine with nine deuterated internal
      standards and injection of 2 MUl. The LC system involved a 2.0 MUm 100 * 2.0 mm
      YMC-UltraHT Hydrosphere-C18 column and gradient elution with a flow rate of 0.5
      ml/min and a total analysis time of 6.0 min. Solvent A consisted of 10 mmol/l
      ammonium formate and 0.005% formic acid, pH 4.8, and Solvent B was methanol with
      10 mmol/l ammonium formate and 0.005% formic acid. The HRMS (Q Exactive, Thermo
      Scientific) used a heated electrospray interface and was operated in positive
      mode with 70 000 resolution. The scan range was 100-650 Da, and data for
      extracted ion chromatograms used +/- 10 ppm tolerance. Product ion monitoring was
      applied for confirmation analysis and for some selected analytes also for
      screening. Method validation demonstrated limited influence from urine matrix,
      linear response within the measuring range (typically 0.1-1.0 MUg/ml) and
      acceptable imprecision in quantification (CV <15%). A few analytes were found to
      be unstable in urine upon storage. The method was successfully applied for
      routine drug testing of 17 936 unknown samples, of which 2715 (15%) contained 52
      of the 148 analytes. It is concluded that the method design based on simple
      dilution of urine and using LC-HRMS in extracted ion chromatogram mode may offer
      an analytical system for urine drug testing that fulfils the requirement of a
      'black box' solution and can replace immunochemical screening applied on
      autoanalyzers. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28493315
TI  - Robust mislabel logistic regression without modeling mislabel probabilities.
AB  - Logistic regression is among the most widely used statistical methods for linear
      discriminant analysis. In many applications, we only observe possibly mislabeled
      responses. Fitting a conventional logistic regression can then lead to biased
      estimation. One common resolution is to fit a mislabel logistic regression model,
      which takes into consideration of mislabeled responses. Another common method is
      to adopt a robust M-estimation by down-weighting suspected instances. In this
      work, we propose a new robust mislabel logistic regression based on gamma
      divergence. Our proposal possesses two advantageous features: (1) It does not
      need to model the mislabel probabilities. (2) The minimum gamma-divergence
      estimation leads to a weighted estimating equation without the need to include
      any bias correction term, that is, it is automatically bias-corrected. These
      features make the proposed gamma-logistic regression more robust in model fitting
      and more intuitive for model interpretation through a simple weighting scheme.
      Our method is also easy to implement, and two types of algorithms are included.
      Simulation studies and the Pima data application are presented to demonstrate the
      performance of gamma-logistic regression.

PMID- 28493316
TI  - A profile of lipid dysregulation in harlequin ichthyosis.

PMID- 28493318
TI  - Zinc-Catalyzed Synthesis of Allylsilanes by Si-H Bond Insertion of Vinyl
      Carbenoids Generated from Cyclopropenes.
AB  - Allylsilanes have long been recognized as valuable building blocks for organic
      synthesis. A zinc-catalyzed reaction of cyclopropenes and hydrosilanes provides a
      convenient route to these versatile unsaturated organosilanes. In this
      transformation, ZnBr2 serves as an efficient catalyst, allowing the generation of
      a zinc vinyl carbenoid intermediate, which is subsequently involved in a Si-H
      bond insertion. The process shows broad scope, and is amenable to substituted and
      functionalized cyclopropenes or the functionalization of polysiloxanes. Moreover,
      zinc-catalyzed carbene insertion into a Ge-H bond is reported for the first time.

PMID- 28493317
TI  - Attachment and Biofilm Formation by Selected Strains of Salmonella enterica and
      Entrohemorrhagic Escherichia coli of Fresh Produce Origin.
AB  - This study compared the abilities of selected Salmonella enterica and
      enterohemorrhagic Escherichia coli (EHEC) strains of fresh produce origin to form
      biofilms on polystyrene surface and to attach to alfalfa and bean sprouts. Each
      of the 7 S. enterica and 4 EHEC inocula (2 mL; 107 CFU/mL) was placed in 6
      different broths in 24-well polystyrene tissue culture plates at 28  degrees C
      for 1 to 7 d. Developed biofilms were quantified using the crystal violet binding
      assay. In a separate experiment, alfalfa and mung bean sprouts (5 g) were exposed
      to 25 mL inocula (107 CFU/mL) of S. enterica or EHEC at 22  degrees C for 2 h
      with shaking at 40 rpm. Contaminated sprouts were thoroughly rinsed and
      homogenized in 0.1% peptone water, and bacteria attached to sprouts were
      enumerated. Biofilm mass accumulated on polystyrene surface increased with
      incubation time (P < 0.05). Among the microbiological media used, LB no salt
      (NaCl) broth better supported biofilm development (P < 0.05). Two EHEC strains
      formed more biofilms than the Salmonella and other two EHEC strains (P < 0.05).
      However, more Salmonella cells (5.66 log CFU/g) attached to sprouts than EHEC
      cells (3.46 log CFU/g). Both Salmonella and EHEC attached in higher numbers to
      mung bean, than alfalfa, sprouts (P < 0.05).

PMID- 28493319
TI  - An Elitist Multiobjective Tabu Search for Optimal Design of Groundwater
      Remediation Systems.
AB  - This study presents a new multiobjective evolutionary algorithm (MOEA), the
      elitist multiobjective tabu search (EMOTS), and incorporates it with
      MODFLOW/MT3DMS to develop a groundwater simulation-optimization (SO) framework
      based on modular design for optimal design of groundwater remediation systems
      using pump-and-treat (PAT) technique. The most notable improvement of EMOTS over
      the original multiple objective tabu search (MOTS) lies in the elitist strategy,
      selection strategy, and neighborhood move rule. The elitist strategy is to
      maintain all nondominated solutions within later search process for better
      converging to the true Pareto front. The elitism-based selection operator is
      modified to choose two most remote solutions from current candidate list as seed
      solutions to increase the diversity of searching space. Moreover, neighborhood
      solutions are uniformly generated using the Latin hypercube sampling (LHS) in the
      bounded neighborhood space around each seed solution. To demonstrate the
      performance of the EMOTS, we consider a synthetic groundwater remediation
      example. Problem formulations consist of two objective functions with continuous
      decision variables of pumping rates while meeting water quality requirements.
      Especially, sensitivity analysis is evaluated through the synthetic case for
      determination of optimal combination of the heuristic parameters. Furthermore,
      the EMOTS is successfully applied to evaluate remediation options at the field
      site of the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts.
      With both the hypothetical and the large-scale field remediation sites, the EMOTS
      based SO framework is demonstrated to outperform the original MOTS in achieving
      the performance metrics of optimality and diversity of nondominated frontiers
      with desirable stability and robustness.

PMID- 28493320
TI  - Post Graduate Course.

PMID- 28493322
TI  - Three-year cancer incidence in Blantyre, Malawi (2008-2010).
AB  - In this paper, we present incidence rates of different cancers calculated for the
      population of Blantyre, Malawi for the period 2008-2010, using data from the
      Malawi Cancer Registry. Active methods were used for case finding, with standard
      checks for accuracy and validity performed in CanReg 4. During this 3-year
      period, a total of 3,711 cases were registered comprising 1,643 men (an estimated
      age-standardized incidence rate (ASR) of 169.8 per 100,000) and 2,068 women (ASR
      238.7 per 105 ). Kaposi sarcoma (KS) was the most common cancer in men (40.5% of
      all cancers in men; ASR 54.0 per 105 ) while cervical cancer was the commonest in
      women (33.3%; ASR 88.6 per 105 ). The incidence rates for esophageal cancer
      remain one of the highest in the world (ASR 30.9 per 100,000 in men, 22.1 per
      100,000 in women). Incidence of cancer of the prostate is relatively low in
      Blantyre (5.1%; ASR 16.4 per 105 ), compared with elsewhere in Africa. In
      childhood, the cancer spectrum is dominated by Burkitt lymphoma (32.5% ASR 90.9
      per 106 ) followed by Wilms tumor (11.3%; ASR 35.9 per 106 ) and pediatric KS
      (11.0%; ASR 31.1 per 106 ). The overall percentage of cases with histological
      verification was 47.5%, a slight improvement from 42.4% in late 1990s also
      indicating successful case finding outside laboratories.

PMID- 28493321
TI  - Local genes for local bacteria: Evidence of allopatry in the genomes of
      transatlantic Campylobacter populations.
AB  - The genetic structure of bacterial populations can be related to geographical
      locations of isolation. In some species, there is a strong correlation between
      geographical distance and genetic distance, which can be caused by different
      evolutionary mechanisms. Patterns of ancient admixture in Helicobacter pylori can
      be reconstructed in concordance with past human migration, whereas in
      Mycobacterium tuberculosis it is the lack of recombination that causes allopatric
      clusters. In Campylobacter, analyses of genomic data and molecular typing have
      been successful in determining the reservoir host species, but not geographical
      origin. We investigated biogeographical variation in highly recombining genes to
      determine the extent of clustering between genomes from geographically distinct
      Campylobacter populations. Whole-genome sequences from 294 Campylobacter isolates
      from North America and the UK were analysed. Isolates from within the same
      country shared more recently recombined DNA than isolates from different
      countries. Using 15 UK/American closely matched pairs of isolates that shared
      ancestors, we identify regions that have frequently and recently recombined to
      test their correlation with geographical origin. The seven genes that
      demonstrated the greatest clustering by geography were used in an attribution
      model to infer geographical origin which was tested using a further 383 UK
      clinical isolates to detect signatures of recent foreign travel. Patient records
      indicated that in 46 cases, travel abroad had occurred <2 weeks prior to
      sampling, and genomic analysis identified that 34 (74%) of these isolates were of
      a non-UK origin. Identification of biogeographical markers in Campylobacter
      genomes will contribute to improved source attribution of clinical Campylobacter
      infection and inform intervention strategies to reduce campylobacteriosis.

PMID- 28493323
TI  - Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints
      of Patients With Rheumatoid Arthritis.
AB  - OBJECTIVE: To characterize the specific structural properties of the erosion
      prone bare area of the human joint, and to search for early microstructural
      changes in this region during rheumatoid arthritis (RA). METHODS: In the initial
      part of the study, human cadaveric hand joints were examined for exact
      localization of the bare area of the metacarpal heads, followed by detection of
      cortical micro-channels (CoMiCs) in this region by high-resolution peripheral
      quantitative computed tomography (HR-pQCT) and, after anatomic dissection,
      validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In
      the second part of the study, the number and distribution of CoMiCs were analyzed
      in 107 RA patients compared to 105 healthy individuals of similar age and sex
      distribution. RESULTS: Investigation by HR-pQCT combined with adaptive
      thresholding allowed the detection of CoMiCs in the bare area of human cadaveric
      joints. The existence of CoMiCs in the bare area was additionally validated by
      micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA
      patients showed significantly more CoMiCs compared to healthy individuals (mean
      +/- SD 112.9 +/- 54.7/joint versus 75.2 +/- 41.9/joint; P < 0.001), with 20-49
      year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy
      individuals older than age 65 years. Importantly, CoMiCs were already found in RA
      patients very early in their disease course, with enrichment in the erosion-prone
      radial side of the joint. CONCLUSION: CoMiCs represent a new form of structural
      change in the joints of patients with RA. Although the number of CoMiCs increases
      with age, RA patients develop CoMiCs much earlier in life, and such changes can
      even occur at the onset of the disease. CoMiCs therefore represent an interesting
      new opportunity to assess structural changes in RA.

PMID- 28493324
TI  - Level-specific amputations and resulting regenerative outcomes in the mouse
      distal phalanx.
AB  - Mouse digit tip regeneration involves an intricate coordinated regrowth of the
      terminal phalanx, nail, dermis and epidermis. During this time, regenerating
      digits undergo wound healing, blastema formation, and differentiation. However,
      the regenerative response of the digit is dependent on the level of the
      amputation. Amputation of <30% of the distal phalanx (P3), with part of the base
      nail remaining, results in extensive digit regeneration. In contrast, >60% P3
      removal results in no regeneration. This level-dependent regenerative ability of
      the mouse digit provides a comparative model between regeneration and non
      regeneration that may enable identification of specific factors critical to
      regeneration. Although the ability to create regenerating and non-regenerating
      conditions has been well established, the regenerative response between these
      regions ("intermediate" zone) has received less scrutiny, and may add insight to
      the regenerative processes, including the degree of histolysis, and the level of
      blastema formation. The objective of this study is then to compare the
      regeneration capacity between amputation levels within the regenerating (<30%),
      intermediate (40-59%), and non-regenerating (>60%) regions. Results indicated
      that regenerative and intermediate amputations led to significant histolysis and
      blastema formation of the distal phalanx 14 days post-amputation. Unlike the
      regenerating digits, intermediate amputations led to incomplete regeneration
      whereby regrowth of the digits were not to the levels of the intact or
      regenerating digits. Non-regenerating amputations did not exhibit significant
      histolysis or blastema formation. Remarkably, the histolytic process resulted in
      day 14 P3 lengths that were similar regardless of the initial amputation over
      19%. The differences in histolysis, blastema formation and injury outcomes were
      also marked by changes in the number of proliferating cells and osteoclasts.
      Altogether, these results indicate that although intermediate amputations result
      in histolysis and blastema formation similar to regenerating digits, the
      resulting cellular composition of the blastema differs, contributing to
      incomplete regeneration.

PMID- 28493325
TI  - Developmental ecology of annual killifish Millerichthys robustus
      (Cyprinodontiformes: Cynolebiidae).
AB  - Populations of annual killifishes persist in temporary water bodies over the dry
      season through the expression of diapause in their drought-resistant embryos.
      Environmental cues may influence expression of the diapause phenotype during
      embryonic incubation. Millerichthys robustus is the only annual killifish
      distributed in North America. The aim of this review is to analyze the ecology of
      M. robustus development and contrast this with that of annual killifishes in
      austral locations. The temporary water bodies inhabited by M. robustus present
      the following environmental conditions: flood, drought, and humidity. During the
      flooding period, the environment presents the lowest temperatures, shortest
      photoperiod, and highest precipitation, and embryos were found in diapause I. The
      drought period features the highest temperatures and lowest precipitation, and
      embryos were found in diapause II. In contrast, during the humid period at the
      beginning of the rainy season, embryos were found in diapause I, II, and III,
      associated with the longer photoperiod and high temperatures. These dynamics of
      the diapause phenotypes can be explained by a combination of the strategies of
      phenotypic plasticity during flood and drought periods, and bet-hedging during
      the humid period. Moreover, the microenvironmental conditions in which embryos
      were buried could influence developmental trajectories. Developmental Dynamics
      246:802-806, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28493326
TI  - Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via
      induction of the extracellular matrix component hyaluronan.
AB  - Epidemiological studies have detected a higher incidence of various tumour
      entities in diabetic patients. However, the underlying mechanisms remain
      insufficiently understood. Glucose-derived pericellular and extracellular
      hyaluronan (HA) promotes tumour progression and development. In our study, we
      tested the hypothesis that a diabetic metabolic state, characterised by
      hyperglycaemia and concomitant aberrant insulin signalling, stimulates tumour
      progression via the induction of HA synthesis. In a streptozotocin-induced
      diabetic nude mouse tumour xenograft model, hyperglycaemia and lack of insulin
      caused an increased formation of tumour-associated HA-matrix, which in turn
      accelerated tumour progression and neoangiogenesis. This process was effectively
      attenuated by treatment with 4-methylumbelliferone, a pharmacological inhibitor
      of HA-synthesis. To define the mechanisms behind these in vivo observations, we
      investigated the impact of hyperglycaemia and insulin on the glucose metabolism
      in oesophageal squamous cell cancer cells (ESCC). Hyperglycaemia induced HA
      synthesis while insulin diminished HA production by directing glucose metabolites
      to glycolysis. Vice versa, inhibition of glycolysis, either by knockdown of the
      glycolytic key enzyme phosphofructokinase or by an experimental abrogation of
      insulin signalling (knockdown of the insulin receptor and long-term treatment
      with insulin) augmented HA synthesis. Consequently, these processes induced
      invasion, anchorage-independent growth and adhesion of ESCC to endothelial cells
      in vitro. Thus, the cellular shift in glucose usage from catabolism of glucose to
      anabolism of HA driven by hyperglycaemia and insulin resistance may represent an
      important link between diabetes and cancer progression. Hence, therapeutical
      inhibition of HA synthesis may represent a promising approach for tumour
      treatment in diabetic patients.

PMID- 28493327
TI  - Burden of illness and healthcare resource use in United States patients with
      sporadic inclusion body myositis.
AB  - INTRODUCTION: We analyzed the burden of illness of sporadic inclusion body
      myositis (sIBM) patients and the costs to the healthcare system. METHODS: A
      retrospective cohort analysis of 333 sIBM patients aged >= 50 years was performed
      using United States (U.S.) claims data. sIBM patients were matched in a 1:5 ratio
      to randomly selected individuals with >=1 healthcare encounter within the year of
      index date. RESULTS: sIBM patients presented with higher rates of disease- and
      muscle-related conditions, such as myalgia, myositis, muscle weakness, dysphagia,
      pneumonia, and falls. Use of healthcare resources, including physical therapy,
      office visits, emergency room (ER) visits, and hospitalizations, was greater in
      sIBM patients. This was also reflected in significantly higher overall healthcare
      costs in the sIBM population driven mainly by more all-cause office visits, all
      cause ER visits and hospitalizations. CONCLUSIONS: sIBM imposes a substantial
      burden on U.S. patients in terms of additional healthcare usage and associated
      costs. Muscle Nerve 56: 861-867, 2017.

PMID- 28493328
TI  - Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine
      Deaminase 2 Sheds New Light on the Disease in Adulthood.
AB  - OBJECTIVE: We aimed to test the relevance of deficiency of adenosine deaminase 2
      (DADA2) in patients with antibody deficiency and describe the clinical picture of
      the disease in adulthood. METHODS: We screened for DADA2 in a cohort of 181
      patients with antibody deficiency with or without vascular lesions using next
      generation sequencing and targeted Sanger sequencing. All mutations were
      confirmed by determining the ADA2 enzymatic activity levels in dried plasma
      spots. Clinical data and laboratory values were collected in a standardized
      format. RESULTS: Following the diagnosis of 2 siblings in the index family, we
      identified 9 additional affected patients with compound heterozygous or
      homozygous CECR1 mutations, containing 6 novel and 4 previously published
      mutations. The patients' age at evaluation ranged from 13 to 51 years, with a
      median age of 22 years. Clinically, we saw a broad phenotype, ranging from
      isolated antibody deficiency to recurrent strokes. All but 1 patient had low
      numbers of memory B cells. Moreover, B cell function seemed to correlate with
      inflammation. CONCLUSION: Taken together, our findings indicate that DADA2
      presents not only with vasculopathy but also with an immunodeficiency of the B
      cell compartment. Therefore, patients with antibody deficiency should be screened
      for DADA2. Anti-tumor necrosis factor treatment might improve immunologic
      features over time and might be considered in patients without vascular
      manifestations but with elevated inflammation markers. Conservative management
      has so far proven to be the choice for our less severely affected adolescent and
      adult DADA2 patients; however, in patients with severe cytopenias and bone marrow
      failure, hematopoietic stem cell transplantation should be considered.

PMID- 28493329
TI  - Risk to heroin users of polydrug use of pregabalin or gabapentin.
AB  - AIM: To examine the risk to heroin users of also using gabapentin or pregabalin
      (gabapentoids). DESIGN: Multi-disciplinary study: we (a) examined trends in drug
      related deaths and gabapentoid prescription data in England and Wales to test for
      evidence that any increase in deaths mentioning gabapentin or pregabalin is
      associated with trends in gabapentoid prescribing and is concomitant with opioid
      use; (b) interviewed people with a history of heroin use about their polydrug use
      involving gabapentin and pregabalin; and (c) studied the respiratory depressant
      effects of pregabalin in the absence and presence of morphine in mice to
      determine whether concomitant exposure increased the degree of respiratory
      depression observed. SETTING: England and Wales. PARTICIPANTS: Interviews were
      conducted with 30 participants (19 males, 11 female). MEASUREMENTS: (a) Office of
      National Statistics drug-related deaths from 1 January 2004 to 31 December 2015
      that mention both an opioid and pregabalin or gabapentin; (b) subjective views on
      the availability, use, interactions and effects of polydrug use involving
      pregabalin and gabapentin; and (c) rate and depth of respiration. RESULTS:
      Pregabalin and gabapentin prescriptions increased approximately 24% per year from
      1 million in 2004 to 10.5 million in 2015. The number of deaths involving
      gabapentoids increased from fewer than one per year prior to 2009 to 137 in 2015;
      79% of these deaths also involved opioids. The increase in deaths was correlated
      highly with the increase in prescribing (correlation coefficient 0.94; 5%
      increase in deaths per 100 000 increase in prescriptions). Heroin users described
      pregabalin as easy to obtain. They suggested that the combination of heroin and
      pregabalin reinforced the effects of heroin but were concerned it induced
      'blackouts' and increased the risk of overdose. In mice, a low dose of S
      pregabalin (20 mg/kg) that did not itself depress respiration reversed tolerance
      to morphine depression of respiration (resulting in 35% depression of
      respiration, P < 0.05), whereas a high dose of S-pregabalin (200 mg/kg) alone
      depressed respiration and this effect summated with that of morphine.
      CONCLUSIONS: For heroin users, the combination of opioids with gabapentin or
      pregabalin potentially increases the risk of acute overdose death through either
      reversal of tolerance or an additive effect of the drugs to depress respiration.

PMID- 28493330
TI  - Improved panels for clinical immune phenotyping: Utilization of the violet laser.
AB  - BACKGROUND: Clinical diagnostic laboratories are subject to numerous regulations
      imposed by government agencies. Laboratory developed tests for flow cytometry
      panels are essentially restricted to the use of analyte-specific reagents (ASR)
      antibodies. With the advances in clinical flow cytometry systems, there is a
      trend toward the utilization of blue/red/violet laser flow systems and 8 to 10
      color panels. Currently, the selection of commercially available ASR antibodies
      for the violet laser is very limited. The market is dominated by Brilliant Violet
      421 (BV421) manufactured by BD Biosciences and Pacific Blue (PB) manufactured by
      Beckman Coulter. In this study, we compare BV421 and PB conjugated ASR
      antibodies. METHODS: Whole blood was stained and acquired on a Gallios flow
      cytometer system. For single color staining, the stain index (SI) was calculated.
      For the two panels, the compensation matrix was calculated and the performance of
      the antibody cocktails analyzed in FCS Express. RESULTS: The results show that
      five out of six tested BV421 conjugated antibodies have significantly higher SI
      than their PB counterparts. Furthermore, BV421 antibodies require less
      compensation for spillover than PB. Finally, BV421 conjugated antibodies give
      better separation between negative and positive populations in the context of an
      8 and 10 color panel without affecting the intensity of the other dyes.
      CONCLUSIONS: Overall, using BV421 conjugated antibodies results in better
      separation between populations compared to PB conjugated antibodies without
      negatively affecting other fluorochromes in our panels. We conclude that the
      BV421 conjugated ASR antibodies are currently the better available option for
      clinical flow panels. (c) 2017 International Clinical Cytometry Society.

PMID- 28493332
TI  - P-value calibration in multiple hypotheses testing.
AB  - As p-values are the most common measures of evidence against a hypothesis, their
      calibration with respect to null hypothesis conditional probability is important
      in order to match frequentist unconditional inference with the Bayesian ones. The
      Selke, Bayarri and Berger calibration is one of the most popular attempts to
      obtain such a calibration. This relies on the theoretical sampling null
      distribution of p-values, which is the well-known Uniform(0,1), but arising only
      for specific sampling models. We generalize this calibration by considering a
      sampling null distribution estimated from the data. It is possible to obtain such
      an empirical null distribution, for instance, in the context of multiple testing
      in which many p-values come from the null model. Such a context is purely
      instrumental for the purposes of p-value calibration, and multiple testing still
      needs to be considered with appropriate techniques. The new calibration proposed
      here still remains a simple analytic formula like the original one under the
      Uniform(0,1) and basically provides a stronger interpretation framework for the
      widely used p-value. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28493333
TI  - Treadmill exercise attenuates 3,4-methylenedioxymethamphetamine-induced memory
      impairment through a decrease apoptosis in male rat hippocampus.
AB  - 3,4-methylenedioxymethamphetamine (MDMA) leads to apoptosis in the hippocampus
      with consequent induction of learning and memory impairment. In this study, we
      have investigated the effects of treadmill exercise on memory in relation to
      apoptosis and oxidative stress in the hippocampi of MDMA-treated rats. Male
      Wistar rats received multiple intraperitoneal (IP) injections of MDMA (10 mg/kg)
      and exercised for one month on a treadmill (simultaneously or asynchronously with
      MDMA). We assessed memory function with the Morris water maze (MWM) test. Lipid
      peroxidation (LPO) and expression of caspase 3, Bax, and Bcl-2 were examined by
      the thiobarbituric acid assay (TBA) and western blot, respectively. Our results
      showed that asynchronous treadmill exercise could significantly improve MDMA
      induced memory impairment in the MWM test. Caspase 3 expression decreased in the
      exercise group compared to the MDMA group. Although MDMA treatment caused an
      increase in the Bax/Bcl-2 ratio, the treadmill exercise reduced this ratio.
      Simultaneous exercise caused a reduction in lipid peroxidation in the
      hippocampus. This data suggests that treadmill exercise can be a useful strategy
      for treating memory impairment in persons with neurodegenerative disease and
      stimulant drug users. (c) 2017 Wiley Periodicals, Inc.

PMID- 28493331
TI  - Pilus biogenesis of Gram-positive bacteria: Roles of sortases and implications
      for assembly.
AB  - Successful adherence, colonization, and survival of Gram-positive bacteria
      require surface proteins, and multiprotein assemblies called pili. These surface
      appendages are attractive pharmacotherapeutic targets and understanding their
      assembly mechanisms is essential for identifying a new class of 'anti-infectives'
      that do not elicit microbial resistance. Molecular details of the Gram-negative
      pilus assembly are available indepth, but the Gram-positive pilus biogenesis is
      still an emerging field and investigations continue to reveal novel insights into
      this process. Pilus biogenesis in Gram-positive bacteria is a biphasic process
      that requires enzymes called pilus-sortases for assembly and a housekeeping
      sortase for covalent attachment of the assembled pilus to the peptidoglycan cell
      wall. Emerging structural and functional data indicate that there are at least
      two groups of Gram-positive pili, which require either the Class C sortase or
      Class B sortase in conjunction with LepA/SipA protein for major pilin
      polymerization. This observation suggests two distinct modes of sortase-mediated
      pilus biogenesis in Gram-positive bacteria. Here we review the structural and
      functional biology of the pilus-sortases from select streptococcal pilus systems
      and their role in Gram-positive pilus assembly.

PMID- 28493334
TI  - Feasibility of an endotracheal tube-mounted camera for percutaneous dilatational
      tracheostomy.
AB  - BACKGROUND: Percutaneous dilatational tracheostomy (PDT) in critically ill
      patients is often led by optical guidance with a bronchoscope. This is not
      without its disadvantages. Therefore, we aimed to study the feasibility of a
      recently introduced endotracheal tube-mounted camera (VivaSightTM-SL, ET View,
      Misgav, Israel) in the guidance of PDT. METHODS: We studied 10 critically ill
      patients who received PDT with a VivaSight-SL tube that was inserted prior to
      tracheostomy for optical guidance. Visualization of the tracheal structures
      (i.e., identification and monitoring of the thyroid, cricoid, and tracheal
      cartilage and the posterior wall) and the quality of ventilation (before puncture
      and during the tracheostomy) were rated on four-point Likert scales. Respiratory
      variables were recorded, and blood gases were sampled before the interventions,
      before the puncture and before the insertion of the tracheal cannula. RESULTS:
      Visualization of the tracheal landmarks was rated as 'very good' or 'good' in all
      but one case. Monitoring during the puncture and dilatation was also rated as
      'very good' or 'good' in all but one. In the cases that were rated 'difficult',
      the visualization and monitoring of the posterior wall of the trachea were the
      main concerns. No changes in the respiratory variables or blood gases occurred
      between the puncture and the insertion of the tracheal cannula. CONCLUSION:
      Percutaneous dilatational tracheostomy with optical guidance from a tube-mounted
      camera is feasible. Further studies comparing the camera tube with bronchoscopy
      as the standard approach should be performed.

PMID- 28493335
TI  - Response of Htr3a knockout mice to antidepressant treatment and chronic stress.
AB  - BACKGROUND AND PURPOSE: It has recently been suggested that 5-HT3 receptor
      blockade enhances the efficacy of selective 5-HT (serotonin) reuptake inhibitor
      (SSRI) antidepressants and may reverse stress-induced deficits in rodents.
      EXPERIMENTAL APPROACH: To further explore this hypothesis, we used mice lacking
      the 5-HT3 receptor (Htr3a KO) and their wild-type (WT) controls to assess their
      response in behavioural paradigms relevant to anxiety and depression. Mice were
      studied under basal, antidepressant treatments and chronic social defeat stress
      (CSDS) conditions. KEY RESULTS: In basal conditions, Htr3a KO mice displayed
      anxiolytic- and antidepressant-like behaviours in the elevated plus maze, the
      social interaction and the forced swim tests (FST), but behaved as WT mice in
      response to acute citalopram in the FST. However, the effects of fluoxetine were
      blunted in Htr3a KO mice in these same tests. In an in vitro electrophysiological
      paradigm, a low-dose citalopram treatment triggered 5-HT1A receptor
      desensitization only in the dorsal raphe nucleus of Htr3a KO, although a high
      dose desensitized 5-HT1A autoreceptor function equally in Htr3a KO and WT mice,
      suggesting that citalopram may become effective at lower doses when 5-HT3
      receptors are inactivated. In addition, Htr3a deletion blocked CSDS-induced
      modification in the cortical expression of two genes involved in oxidative
      stress, CaMKIIa and SOD1. CONCLUSIONS AND IMPLICATIONS: Taken together, these
      data show that Htr3a deletion promotes SSRI efficacy and prevents the occurrence
      of stress-induced deleterious effects, suggesting that the 5-HT3 receptor may
      represent an interesting target for the treatment of stress-related disorders.

PMID- 28493336
TI  - De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal
      Correctional Clients.
AB  - Adult antisocial behavior is almost always predated by delinquency during
      childhood or adolescence; however, there is also evidence of adult-onset criminal
      offending. This study examined this controversial subgroup of offenders using
      self-reported and official data from a total population of federal correctional
      clients selected from the Midwestern United States. Difference of means t-tests,
      chi-square tests, and logistic regression models found that 11.7% of clients had
      an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring
      at age 60 years or older. This group-introduced as de novo advanced adult-onset
      offenders-had high socioeconomic status, mixed evidence of adverse childhood
      experiences, and virtually no usage of drugs with the exception of alcohol. These
      offenders were primarily convicted of social security and white-collar crimes and
      evinced remarkably low psychopathology and criminal risk. More research is needed
      to replicate the phenomenon of de novo advanced adult-onset offending.

PMID- 28493337
TI  - Cas6 processes tight and relaxed repeat RNA via multiple mechanisms: A
      hypothesis.
AB  - RNA molecules are flexible yet foldable. Proteins must cope with this structural
      duality when forming biologically active complexes with RNA. Recent studies of
      the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-mediated
      RNA immunity illustrate some remarkable mechanisms with which proteins interact
      with RNA. Currently known structures of CRISPR-Cas6 endoribonucleases bound with
      RNA suggest a conserved protein recognition mechanism mediated by RNA stem-loops.
      However, a survey of CRISPR RNA reveals that many repeats either lack a
      productive stem-loop (Relaxed) or possess stable but inhibitory structures
      (Tight), which raises the question of how the enzyme processes structurally
      diverse RNA. In reviewing recent literature, we propose a bivalent trapping and
      an unwinding mechanism for CRISPR-Cas6 to interact with the Relaxed and the Tight
      repeat RNA, respectively. Both mechanisms aim to create an identical RNA
      conformation at the cleavage site for accurate processing.

PMID- 28493338
TI  - Age-related changes of gustatory function depend on alteration of neuronal
      circuits.
AB  - Studies on age-related gustatory function report a reduction of the taste
      function, but the degeneration of the peripheral papillae alone cannot explain
      this reduction. In the present study, we apply psychophysics and gustatory event
      related potentials (gERPs) to explore age-related differences in the processing
      of gustatory information as indicated by the cerebral sources of the gERP. A
      total of 96 subjects (47 female), subdivided into four groups with increasing
      age, participated in the study. After olfactory and gustatory screening for
      normal function, the subjects were invited to two sessions of gERP acquisition.
      They received a randomized combination of five isointense basic tastants that
      were presented at a medium level. At the same time, we recorded scalp
      electroencephalography (EEG) from 128 scalp locations. Psychophysical testing for
      smell and taste function exhibited a significant decrease with age. Topographical
      analyses of the EEG delineated four basic topographical maps that explained the
      processing of taste in the pre-decline age range, with sources inside the
      relevant gustatory areas. The age-related change of gustatory processing was
      associated with the absence of a specific map with sources inside the cerebellum
      and posterior insula, and the temporal broadening of a map with sources in the
      bilateral inferior frontal gyrus. These results confirm the hypothesis that the
      reduction of taste function with aging is not only due to degradation of
      gustatory peripheral tissues but is also related to different neural signatures
      in the central nervous system.

PMID- 28493342
TI  - Rapid-deployment aortic valve replacement versus standard bioprosthesis
      implantation.
AB  - OBJECTIVE: To compare the outcome and the 1-year hemodynamic results of the rapid
      deployment Intuity valve versus the Perimount Magna bioprosthesis in matched
      populations. METHODS: Between March 2014 and May 2015, 32 patients underwent
      aortic valve replacement with the Intuity valve (Intuity-group). These patients
      were compared to a matched population of Perimount valves implanted during the
      same period of time (Perimount-group). Clinical data were compared and
      echocardiographic 1-year follow-up was performed. RESULTS: There were more female
      patients in the Intuity-group (47% vs 22%, p = 0.035); mean age was 78 +/- 5.6
      and 72.5 +/- 6 years in the Intuity-group and Perimount-group (p < 0.001);
      coronary disease was more common in the Intuity-group (65% vs 25%, p = 0.005).
      Other characteristics were similar. Implants were 100% successful. Mean cross
      clamp (50.3 +/- 25 vs 53 +/- 22 min, p = 0.004), cardiopulmonary bypass (68 +/-
      27 vs 72 +/- 31.8 min; p = 0.006), and surgical times (156.8 +/- 54 vs 165 +/- 40
      min; p = 0.018) were shorter with the Intuity despite more concomitant
      procedures. Mean valve size was 23.7 mm (Intuity-group) and 24.1 mm (Perimount
      group); hospital mortality was zero (Intuity-group) and 3% (Perimount-group); new
      pacemaker implants were 6% (Intuity) and 3% (Perimount) (p = 0.55) and hospital
      stay was equivalent. Mean gradients were: 9.9 +/- 3.4 (Intuity) versus 12.5 +/-
      3.8 mmHg (Perimount) (p = 0.022) at discharge and 9 +/- 4 mmHg (Intuity) versus
      14 +/- 4 mmHg (Perimount) (p = 0.02) at follow-up. At discharge, one Intuity
      valve had 3+ aortic insufficiency (AI) which was unchanged at 1 year and will
      require an intervention. Another patient had 1 + AI which progressed to 2+ at 1
      year. There were no paravalvular leaks in the Perimount valves at discharge and
      follow-up. CONCLUSION: Intuity valves showed lower gradients compared to
      Perimount valves with the same mean size. Paravalvular leaks identified at the
      time of implantation in Intuity valves need to be addressed at the time of
      surgery.

PMID- 28493341
TI  - Design and validation of the first cell-impermeant melatonin receptor agonist.
AB  - BACKGROUND AND PURPOSE: The paradigm that GPCRs are able to prolong or initiate
      cellular signalling through intracellular receptors recently emerged. Melatonin
      binds to G protein-coupled MT1 and MT2 receptors. In contrast to most other
      hormones targeting GPCRs, melatonin and its synthetic analogues are amphiphilic
      molecules easily penetrating into cells, but the existence of intracellular
      receptors is still unclear mainly due to a lack of appropriate tools.
      EXPERIMENTAL APPROACH: We therefore designed and synthesized a series of
      hydrophilic melatonin receptor ligands coupled to the Cy3 cyanin fluorophore to
      reliably monitor its inability to penetrate cells. Two compounds, one lipophilic
      and one hydrophilic, were then functionally characterized in terms of their
      affinity for human and murine melatonin receptors expressed in HEK293 cells and
      their signalling efficacy. KEY RESULTS: Among the different ligands, ICOA-13
      showed the desired properties as it was cell-impermeant and bound to human and
      mouse MT1 and MT2 receptors. ICOA-13 showed differential activities on melatonin
      receptors ranging from partial to full agonistic properties for the Gi /cAMP and
      ERK pathway and beta-arrestin 2 recruitment. Notably, ICOA-13 enabled us to
      discriminate between Gi /cAMP signalling of the MT1 receptor initiated at the
      cell surface and neuronal mitochondria. CONCLUSIONS AND IMPLICATIONS: We report
      here the first cell-impermeant melatonin receptor agonist, ICOA-13, which allows
      us to discriminate between signalling events initiated at the cell surface and
      intracellular compartments. Detection of mitochondrial MT1 receptors may have an
      important impact on the development of novel melatonin receptor ligands relevant
      for neurodegenerative diseases, such as Huntington disease.

PMID- 28493343
TI  - Direct Observation of Confined I- ???I2 ???I- Interactions in a Metal-Organic
      Framework: Iodine Capture and Sensing.
AB  - Herein a strategy is reported for capturing and sensing iodine by strong I- ???I2
      ???I- interaction, confined in a metal-organic framework, [Tb(Cu4 I4 )(ina)3
      (DMF)] (1) (ina=isonicotinate). As revealed by single-crystal X-ray
      crystallography, the uptaken I2 molecules directly contact the {Cu4 I4 }n chains,
      virtually forming an electronically polarizable tetraiodide anion (I42- ) through
      strong I- ???I2 ???I- interaction. As such, a quasi-copper-iodide layer of {Cu4
      I5 }n with semiconducting characteristics results, leading to a significant
      enhancement (Deltasigma =107 times) in electrical conductivity over the I2 -free
      1. The effect observed is several orders of magnitude higher than those reported
      due to iodine???aromatic interactions (Deltasigma =102 times) and by interactions
      between I2 and a redox-active metal centre (Deltasigma =104 times). The drastic
      enhancement in electrical conductivity was used to switch on/off an LED bulb,
      suggesting the possibility of electrically sensing I2 .

PMID- 28493344
TI  - Recreational Sporting Activity Vehicle-Related Deaths.
AB  - Deaths occurring in the setting of nonprofessional, vehicle-related, recreational
      sporting activities occurring on land or in water during warm or winter months
      represent a diverse group of cases. These deaths tend to involve scenarios where
      the participants are purposefully attempting to enjoy themselves prior to
      experiencing sudden, catastrophic accidents resulting in lethal outcomes.
      Ultimately, many of the deaths are related to the high speed at which these
      vehicle-related activities normally occur. Three broad categories of factors may
      play contributory roles in death: human factors, vehicle factors, and
      environmental factors. A series of selected cases are presented, representing
      examples of varying activity types, involving motorized and nonmotorized
      vehicles, land and water activities, and warm weather and cold weather
      environments. For each case, the various human, vehicle and environmental factors
      believed to be contributory to the accident are considered, and strategies for
      prevention of these and similar deaths involving recreational sporting vehicles
      are presented.

PMID- 28493345
TI  - IL-10 expression in pyramidal neurons after neuropathogenic coronaviral
      infection.
AB  - The apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus
      is induced after infection with Mu-3 virus (Mu-3), a neuropathogenic strain of
      the JHM virus (JHMV), at 4-5 days post-inoculation (dpi). The viral antigens in
      the hippocampus are mainly found in the CD11b-positive cells distributed in the
      stratum oriens located outside the pyramidal layer, and only a few pyramidal
      neurons are infected. Furthermore, the apoptotic cells, indicated as showing
      caspase 3 (Cas3) activation, consist of a high number of uninfected cells.
      Therefore, it is considered that the apoptotic lesions occur through the indirect
      effects of infection, and not as a result of direct infection with Mu-3, similar
      to the reported neuronal apoptosis in the hippocampus after other types of
      infection. The apoptosis in the pyramidal neurons is accompanied by various types
      of proinflammatory cytokines depending on the causative agents. Thus, the local
      expression of proinflammatory cytokines was studied, revealing no correlation in
      the distribution of cytokine expression with the subregions showing apoptosis.
      However, the anti-inflammatory cytokine IL-10 was produced by pyramidal neurons
      of CA2 and CA3 at 3 dpi when there is no destructive change or viral invasion in
      the hippocampus.

PMID- 28493346
TI  - No effect of targeted memory reactivation during slow-wave sleep on emotional
      recognition memory.
AB  - Recent work has suggested that the benefits of sleep for memory consolidation are
      enhanced for highly salient (versus non-salient) memories. Using a technique
      known as targeted memory reactivation, it is possible to selectively strengthen
      newly learned memories by re-exposing the sleeping brain to auditory cues. The
      aim of the current study was to examine whether emotionally salient memories are
      also more responsive to targeted memory reactivation in slow-wave sleep than
      neutral memories. In an initial training phase, participants memorised
      emotionally negative and neutral pictures, which were each paired with a
      semantically related sound. Recognition for the pictures was assessed before and
      after a 90-min nap opportunity, during which half the sounds were re-presented
      during slow-wave sleep (as assessed via online polysomnographic sleep
      monitoring). We observed no effect of targeted memory reactivation on the
      recognition of emotionally negative or neutral memories. Our results highlight
      the importance of the memory paradigm used to assess targeted memory
      reactivation, and suggest that the robust and durable nature of recognition
      memory may make it an insensitive measure of behavioural targeted memory
      reactivation benefits. To fully assess the impacts of targeted memory
      reactivation on emotional memory processing in sleep, future studies should adopt
      experimental paradigms that maximise the salience of emotional stimuli while also
      providing a sensitive index of memory accuracy.

PMID- 28493347
TI  - Effects of different loading protocols on the secondary stability and peri
      implant bone density of the single implants in the posterior maxilla.
AB  - BACKGROUND: Immediate or early loading of dental implants becomes a clinically
      feasible concept. PURPOSE: The aim was to evaluate the effects of different
      loading protocols (immediate, early, and delayed) on secondary stability and peri
      implant bone density of single implants in the posterior maxilla. MATERIALS AND
      METHODS: Thirty-nine implants (Dentium, South-Korea) were placed in 39 patients.
      After placement, implant stability values (ISQ) and baseline peri-implant bone
      density values derived from cone-beam computed tomography were recorded. Thirteen
      implants were included randomly in each loading groups. The secondary ISQ values
      were recorded during follow-up visits. Peri-implant bone density values were
      measured 1 year after placement again. Data was statistically analyzed. RESULTS:
      Immediate-loaded group showed the lowest ISQ values, 1 month after placement.
      During the next follow-up visits, delayed-loaded group showed the lowest ISQ
      values while other groups showed comparable results. Early loading increased the
      peri-implant bone density greater than the other groups. CONCLUSIONS: The peri
      implant bone of early-loaded implants was significantly denser than that of
      immediate- and delayed-loaded implants, 1 year after placement. Density increment
      can be judged as the radiological findings of loaded-bone, which may also reduce
      the need for histomorphometric analysis of human biopsy to evaluate the bone
      reaction around the implants.

PMID- 28493348
TI  - Effect of Eye Opening on Single-Unit Activity and Local Field Potentials in the
      Subthalamic Nucleus.
AB  - BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an
      established treatment in Parkinson's disease (PD). We investigate the effect of
      eye opening on neuronal activity and local field potentials (LFPs) in the STN.
      METHODS: We prospectively enrolled 25 PD patients undergoing STN DBS in our
      institution. During DBS, single-unit activity (SUA) and LFPs were measured when
      eyes were open and closed. As movement is known to result in changes in LFPs, we
      tested response to eye opening in the presence and absence of movement. RESULTS:
      Neither eye state nor arm movement has a significant influence on SUA recordings.
      There is a statistically significant interaction between eye state and arm
      movement (p < 0.05). In the presence of movement, STN SUA increase when eyes open
      (p < 0.05). When eyes are closed, STN SUA decrease with movement (p < 0.05). STN
      theta LFP oscillations decrease when eyes are open compared to closed,
      irrespective of movement status (p < 0.05). DISCUSSION: STN activity is
      influenced by eye state and arm movement. It is unclear whether this is
      attributed to a change in the STN's role in oculomotor control or from a change
      in attentional state. Understanding how physiologic normal activity alters neural
      activity is critical for the optimization of DBS therapy, particularly in closed
      loop neuromodulation.

PMID- 28493350
TI  - Reproductive character displacement of female, but not male song discrimination
      in an avian hybrid zone.
AB  - Divergence of male sexual signals and female preferences for those signals often
      maintains reproductive boundaries between closely related, co-occurring species.
      However, contrasting sources of selection, such as interspecific competition, can
      lead to weak divergence or even convergence of sexual signals in sympatry. When
      signals converge, assortative mating can be maintained if the mating preferences
      of females diverge in sympatry (reproductive character displacement; RCD), but
      there are few explicit examples. Pied flycatchers (Ficedula hypoleuca) are
      sympatric with collared flycatchers (F. albicollis) on the Baltic island of
      Oland, where males from both species compete over nestboxes, their songs
      converge, and the two species occasionally hybridize. We compare song
      discrimination of male and female pied flycatchers on Oland and in an allopatric
      population on the Swedish mainland. Using field choice trials, we show that male
      pied flycatchers respond similarly to the songs of both species in sympatry and
      allopatry, while female pied flycatchers express stronger discrimination against
      heterospecific songs in sympatry than in allopatry. These results are consistent
      with RCD of song discrimination of female pied flycatchers where they co-occur
      with collared flycatchers, which should maintain species assortative mating
      despite convergence of male sexual signals.

PMID- 28493349
TI  - Adult acute supraglottitis: Analysis of 358 patients for predictors of airway
      intervention.
AB  - OBJECTIVES/HYPOTHESIS: Acute supraglottitis is a potentially life-threatening
      condition due to rapid onset upper airway obstruction. The study aimed to
      characterize adult acute supraglottitis patients and to recognize factors
      associated with an aggressive disease course. STUDY DESIGN: Retrospective chart
      review. METHODS: All adult acute supraglottitis patients admitted to a single
      academic medical center between 2000 and 2014 were included and their medical
      charts reviewed. The main outcome measures were airway intervention and
      mortality. RESULTS: Three hundred fifty-eight patients were enrolled. Mean age
      was 53 years (range, 16-92 years), with 62.8% males. Sore throat (79%) and
      dysphagia (70.9%) were the most common symptoms. Stridor (3.6%), tachypnea
      (5.7%), and dyspnea (6.4%) were uncommon but significantly associated with airway
      intervention. The epiglottis was most commonly involved (67%). Involvement of the
      epiglottis and aryepiglottic folds showed a trend of correlation to airway
      intervention. Blood glucose levels, C-reactive protein (CRP) levels, and relative
      neutrophilia were significantly higher in patients admitted to the intensive care
      unit or requiring airway intervention. Thirty-four patients (9.5%) required
      intensive care unit admission. Sixteen patients (4.4%) required airway
      intervention. Recurrent episodes of supraglottitis, seen in 19 patients, were
      more common in males (P = .048), and tended to have a more severe clinical
      course, requiring more airway interventions (P = .005) and intensive care unit
      admissions (P = .016). CONCLUSIONS: The typical high risk patient-a male, with
      dyspnea and stridor, presenting with edema of the epiglottis and aryepiglottic
      folds, elevated CRP, hyperglycemia, and a history of recurrent episodes-should
      warrant more aggressive treatment and closer observation. LEVEL OF EVIDENCE: 4
      Laryngoscope, 127:2106-2112, 2017.

PMID- 28493351
TI  - Human Zika and West Nile virus neurological infections: What is the difference?
AB  - The recent epidemic of West Nile Virus (WNV) infection in the United States was
      associated with severe neurological disease in immunocompromised hosts, while the
      emergence of Zika virus infection in the Americas has been notable for an
      association with increased microcephaly in the fetuses of infected mothers. Rare
      autopsies of WNV infected humans have shown multiple organ involvement with a
      clear neurotropism. We have recently had the opportunity to examine the
      distribution of Zika virus in autopsies of newborns from infected pregnancies.
      While both viruses infect multiple organs, Zika appears to cause neurological
      disease in the fetus through two different mechanisms. Infection during the first
      trimester showed the potential to infect neural progenitor cells causing severe
      developmental abnormalities, while infection later in gestation was associated
      with meningeal infection and destructive ischemic lesions of the brain. Both
      viruses infect kidney tubules but Zika shares a prominent hepatotropism
      characteristic of other flaviviruses (e.g., Dengue). Limited transplacental Zika
      infection would be consistent with restriction to primary maternal infections
      with high viremia. In the absence of a vaccine, restriction of travel by
      immunosuppressed and pregnant non-immune individuals to endemic regions seems
      prudent.

PMID- 28493353
TI  - Abstracts of the 51st Annual Scientific Meeting of the European Society for
      Clinical Investigation, Genoa, Italy, 17th - 19th May 2017.

PMID- 28493352
TI  - Should preoperative optimization of colorectal cancer patients supersede the
      demands of the 62-day pathway?

PMID- 28493354
TI  - Acral angioleiomyoma with tumoral calcinosis: a complication of the insertional
      Achilles tendinopathy.

PMID- 28493355
TI  - Consideration of difficulties and exit strategies in a case of face
      allotransplantation resulting in failure.
AB  - We describe the first rescue procedure in a case of total face
      allotransplantation. The recipient was a 54-year-old man with severe
      disfigurement of the entire face following an accidental gunshot injury 5 years
      previously. The large defect included the maxilla, mandible, and mid-face. Full
      face procurement was performed from a multiorgan cadaveric donor and was
      allotransplanted to the recipient. The post-transplant induction
      immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate
      mofetil, and prednisone, while maintenance was provided by the last three of
      these. Although the early postoperative period was uneventful, squamous cell
      carcinoma developed in the upper and lower extremities in the fifth postoperative
      month, and post-transplant lymphoproliferative disorder (PTLD) occurred in the
      sixth month postoperatively. Malignancies were treated, involving both surgical
      and medical approaches. The patient developed opportunistic pulmonary and
      cerebellar aspergillosis. In order to reduce the adverse affects and metabolic
      and immunological load, the transplanted face was removed and replaced with a
      free flap. Although the early postoperative period was promising, with the
      transferred flap surviving totally and all vital signs and general status
      appearing to be improving, the patient was eventually lost due to complicated
      infectious and metabolic events. Although this case was unsuccessful, we suggest
      that the immunological and metabolic load should be reduced as soon as stable
      medical conditions are established in case of diagnosis of a situation involving
      a high rate of mortality, such as PTLD and untreatable opportunistic infections.
      This should include withdrawal of all immunosuppressive drugs and removal of all
      allotransplanted tissues.

PMID- 28493356
TI  - Closing the cervical cancer disparity gap.

PMID- 28493357
TI  - Public Health Nursing and Transnational Agendas: Local to Global Health Advocacy.

PMID- 28493358
TI  - Structural identification of degradants of moexipril by LC-MS/MS.
AB  - A gradient LC-MS method was developed for the identification and characterization
      of degradants of moexipril using liquid chromatography electrospray ionization
      tandem mass spectrometry (LC/ESI-MS/MS). Moexipril was subjected to hydrolysis
      (acid, base and neutral), oxidation, photolytic and thermal degradation
      conditions as mentioned in ICH guidelines Q1A (R2). The drug degraded under
      hydrolysis, oxidation and photolytic conditions, but it was stable under thermal
      conditions. In total, five degradants were formed and separated on an Agilent XDB
      C-18 column (4.6 * 150 mm, 5 MUm) in a gradient elution method. Four degradants
      (D1, D2, D4 and D5) under acidic conditions, three degradants (D2, D3 and D4)
      under basic conditions and three degradants (D1, D4 and D5) under neutral and
      oxidative stress conditions were formed. In addition, two degradants (D4 and D5)
      were formed under photolytic stress conditions. To elucidate the structures of
      degradants, fragmentation of moexipril and its degradants was studied using LC
      MS/MS experiments and accurate mass measurements (HRMS) data. The fragment ions
      in the product ion tandem mass spectra of all the degradants were compared with
      those of moexipril and assigned the probable structures for the degradants.

PMID- 28493359
TI  - Verbal and Non-verbal Fluency in Adults with Developmental Dyslexia: Phonological
      Processing or Executive Control Problems?
AB  - The executive function of fluency describes the ability to generate items
      according to specific rules. Production of words beginning with a certain letter
      (phonemic fluency) is impaired in dyslexia, while generation of words belonging
      to a certain semantic category (semantic fluency) is typically unimpaired.
      However, in dyslexia, verbal fluency has generally been studied only in terms of
      overall words produced. Furthermore, performance of adults with dyslexia on non
      verbal design fluency tasks has not been explored but would indicate whether
      deficits could be explained by executive control, rather than phonological
      processing, difficulties. Phonemic, semantic and design fluency tasks were
      presented to adults with dyslexia and without dyslexia, using fine-grained
      performance measures and controlling for IQ. Hierarchical regressions indicated
      that dyslexia predicted lower phonemic fluency, but not semantic or design
      fluency. At the fine-grained level, dyslexia predicted a smaller number of
      switches between subcategories on phonemic fluency, while dyslexia did not
      predict the size of phonemically related clusters of items. Overall, the results
      suggested that phonological processing problems were at the root of dyslexia
      related fluency deficits; however, executive control difficulties could not be
      completely ruled out as an alternative explanation. Developments in research
      methodology, equating executive demands across fluency tasks, may resolve this
      issue. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28493360
TI  - Ethical reflection for medical electives.
AB  - BACKGROUND: Forty per cent of UK medical students undertake their elective in a
      developing country. Although these opportunities are often rewarding, students
      encounter ethical questions, both in preparation and undertaking these projects.
      The British Medical Association highlights three key ethical considerations for
      elective students: clinical challenges, cultural challenges and impact on the
      host institution. This report reflects on these considerations in the context of
      a 4-week medical elective conducted by UK medical students in the Solomon
      Islands. METHODS: Daily interviews were conducted with a focus group of six
      medical students in the Solomon Islands over a 4-week elective period.
      Descriptive analysis identified key themes. FINDINGS: Students were aware of
      guidelines stating that they must act within their competency, but found it
      difficult to assess their own skills and capacities in unfamiliar non-UK
      settings. Culturally different societal and medical norms proved particularly
      challenging. The impact of the student elective on the host hospital was also
      larger than anticipated. DISCUSSION: In UK medical education, formal assessment
      sets the benchmark for competency. Assessments cannot cover every situation
      encountered on elective, and so students must therefore develop an alternative
      benchmark to measure their ability. The lack of research into the impact of
      electives on host institutions makes assessing the ethical nature of electives
      challenging. The British Medical Association highlights three key ethical
      considerations for elective students CONCLUSION: Prospective elective students
      would benefit from pre-departure training on self-assessment of competency and
      cultural awareness. UK medical schools have an ethical duty to encourage students
      to consider the impact of their elective placements on host institutions.

PMID- 28493361
TI  - Vertically Aligned Niobium Nanowire Arrays for Fast-Charging Micro
      Supercapacitors.
AB  - Planar micro-supercapacitors are attractive for system on chip technologies and
      surface mount devices due to their large areal capacitance and energy/power
      density compared to the traditional oxide-based capacitors. In the present work,
      a novel material, niobium nanowires, in form of vertically aligned electrodes for
      application in high performance planar micro-supercapacitors is introduced.
      Specific capacitance of up to 1 kF m-2 (100 mF cm-2 ) with peak energy and power
      density of 2 kJ m-2 (6.2 MJ m-3 or 1.7 mWh cm-3 ) and 150 kW m-2 (480 MW m-3 or
      480 W cm-3 ), respectively, is achieved. This remarkable power density,
      originating from the extremely low equivalent series resistance value of 0.27
      Omega (2.49 uOmega m2 or 24.9 mOmega cm2 ) and large specific capacitance, is
      among the highest for planar micro-supercapacitors electrodes made of
      nanomaterials.

PMID- 28493363
TI  - Salinity fluctuation influencing biological adaptation: growth dynamics and Na+
      /K+ -ATPase activity in a euryhaline bacterium.
AB  - Although salinity fluctuation is a prominent characteristic of many coastal
      ecosystems, its effects on biological adaptation have not yet been fully
      recognized. To test the salinity fluctuations on biological adaptation,
      population growth dynamics and Na+ /K+ -ATPase activity were investigated in the
      euryhaline bacterium Idiomarina sp. DYB, which was acclimated at different
      salinity exposure levels, exposure times, and shifts in direction of salinity.
      Results showed: (1) bacterial population growth dynamics and Na+ /K+ -ATPase
      activity changed significantly in response to salinity fluctuation; (2) patterns
      of variation in bacterial growth dynamics were related to exposure times, levels
      of salinity, and shifts in direction of salinity change; (3) significant
      tradeoffs were detected between growth rate (r) and carrying capacity (K) on the
      one hand, and Na+ /K+ -ATPase activity on the other; and (4) beneficial
      acclimation was confirmed in Idiomarina sp. DYB. In brief, this study
      demonstrated that salinity fluctuation can change the population growth dynamics,
      Na+ /K+ -ATPase activity, and tradeoffs between r, K, and Na+ /K+ -ATPase
      activity, thus facilitating bacterial adaption in a changing environment. These
      findings provide constructive information for determining biological response
      patterns to environmental change.

PMID- 28493362
TI  - Associations of prenatal and early life dietary inflammatory potential with
      childhood adiposity and cardiometabolic risk in Project Viva.
AB  - BACKGROUND: Limited information exists regarding the association between early
      life diet and cardiometabolic risk. OBJECTIVES: Examine associations of dietary
      inflammatory index (DII) in pregnancy and early childhood (3-5 years) with
      adiposity, blood pressure and metabolic markers in mid-childhood (6-10 years).
      METHODS: Among 992 mother-child pairs from Project Viva, a pre-birth cohort, we
      examined associations of DII scores with outcomes using multivariable linear
      regression adjusted for child age and sex and maternal age, BMI, education,
      parity, smoking, race and income. RESULTS: Mean (SD) maternal DII in pregnancy
      was -2.6(1.4) units and in child DII in early childhood was 0.3(0.7). Mean mid
      childhood BMI z-score was 0.40(0.98) units. In boys only, DII in early childhood
      was associated with higher BMIz (adjusted beta = 0.16 units per unit DII, 95%CI
      0.02, 0.29), waist circumference (0.93 cm; -0.07, 1.92) and skin fold thicknesses
      (1.12 mm; 0.01, 2.23). Dietary inflammatory index in the highest quartiles during
      both pregnancy and in early childhood, compared to the lowest quartiles, was
      associated with higher waist circumference (2.4 cm; 0.14, 4.6) in all children,
      and BMIz in boys (0.78 units; 0.34, 1.22). Associations with BP and metabolic
      markers were null. CONCLUSIONS: A pro-inflammatory diet in pregnancy and early
      childhood may promote the development of adiposity.

PMID- 28493365
TI  - Polymeric spatial resolution test patterns for mass spectrometry imaging using
      nano-thermal analysis with atomic force microscopy.
AB  - RATIONALE: As the spatial resolution of mass spectrometry imaging technologies
      has begun to reach into the nanometer regime, finding readily available or easily
      made resolution reference materials has become particularly challenging for
      molecular imaging purposes. This paper describes the fabrication,
      characterization and use of vertical line array polymeric spatial resolution test
      patterns for nano-thermal analysis/atomic force microscopy/mass spectrometry
      chemical imaging. METHODS: Test patterns of varied line width (0.7 or 1.0 MUm)
      and spacing (0.7 or 1.0 MUm) were created in an ~1-MUm-thick poly(methyl
      methacrylate) thin film using electron beam lithography. The patterns were
      characterized by scanning electron microscopy, energy-dispersive X-ray
      spectroscopy, atomic force microscopy topography and nano-thermal analysis/mass
      spectrometry imaging. RESULTS: The efficacy of these polymeric test patterns for
      the advancement of chemical imaging techniques was illustrated by their use to
      judge the spatial resolution improvement achieved by heating the ionization
      interface of the current instrument platform. The spatial resolution of the mass
      spectral chemical images was estimated to be 1.4 MUm, based on the ability to
      statistically distinguish 0.7-MUm-wide lines separated by 0.7-MUm-wide spacings
      in those images when the interface cross was heated to 200 degrees C.
      CONCLUSIONS: This work illustrates that e-beam lithography is a viable method to
      create spatial resolution test patterns in a thin film of high molecular weight
      polymer to allow unbiased judgment of intra-laboratory advancement and/or inter
      laboratory comparison of instrument advances in nano-thermal analysis/atomic
      force microscopy/mass spectrometry chemical imaging. Published in 2017. This
      article is a U.S. Government work and is in the public domain in the USA.

PMID- 28493364
TI  - Explicating the role of empathic processes in substance use disorders: A
      conceptual framework and research agenda.
AB  - ISSUES: Elucidating the role of empathic processes in developmental pathways to
      substance use disorders could have important implications for prevention.
      APPROACH: We searched the biomedical and social sciences literature to determine
      what is known about empathy and psychopathological manifestations of severe lack
      of empathy in the initiation, development and maintenance of psychoactive
      substance use. Thirty-seven empirical studies were identified and formally
      reviewed. KEY FINDINGS: Adults with alcohol and stimulant use disorders exhibited
      detectable impairments in both cognitive and affective empathy, measured
      behaviourally, neuroanatomically and by self-report, relative to controls. There
      were no developmental studies specifically designed to test the role of empathy
      in substance use pathways, but several studies that included measures of empathy
      suggest that empathy may be protective. Studies on severe empathic deficits were
      mixed regarding a unique role of empathy in substance use trajectories,
      independent of interpersonal style, impulsivity and social deviance. Implications
      and Conclusions. In the context of findings and methodological limitations of
      this review, we recommend more rigorous examination of empathy across the
      spectrum of substance use behaviour. Future work should utilise the following:
      (i) prospective assessment of empathic capacity in substance abusers during and
      following treatment; (ii) large, developmentally based prospective designs
      beginning prior to substance initiation incorporating multiple measures of
      empathy; (iii) assessment of the moderating role of gender, race and ethnicity;
      and (iv) prospective study of empathy in children at elevated risk for substance
      use disorders. [Massey SH, Newmark RL, Wakschlag LS. Explicating the role of
      empathic processes in substance use disorders: A conceptual framework and
      research agenda.

PMID- 28493366
TI  - Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated
      sinonasal carcinomas.
AB  - Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with
      limited treatment options and poor outcome. A morphological spectrum of 47
      sinonasal tumours including 17 (36.2%) SNUCs was analysed at genomic level.
      Thirty carcinomas (cohort 1) were subjected to a hybridization exon-capture next
      generation sequencing assay (MSK-IMPACTTM ) to interrogate somatic variants in
      279 or 410 cancer-related genes. Seventeen sinonasal tumours (cohort 2) were
      examined only for the presence of IDH1/2 exon 4 mutations by Sanger sequencing.
      IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs,
      in two (20%) poorly-differentiated carcinomas with glandular/acinar
      differentiation, and in one of two high-grade neuroendocrine carcinomas, large
      cell type (HGNECs). No IDH2 mutation was detected in any of five olfactory
      neuroblastomas or in any of five SMARCB1-deficient carcinomas. Among 12 IDH2
      mutated cases in cohort 1, five (41.7%) harboured co-existing TP53 mutations,
      four (33.3%) CDKN2A/2B loss-of-function alterations, four (33.3%) MYC
      amplification, and three (25%) had concurrent SETD2 mutations. AKT1 E17K and KIT
      D816V hotspot variants were each detected in one IDH2-mutated SNUC. The vast
      majority of SNUCs and variable proportions of other poorly-differentiated
      sinonasal carcinomas may be amenable to IDH2-targeted therapy. Copyright (c) 2017
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 28493367
TI  - Granulocyte-macrophage colony-stimulating factor, a potent adjuvant for
      polarization to Th-17 pattern: an experience on HIV-1 vaccine model.
AB  - Cytokines are mediators for polarization of immune response in vaccines. Studies
      show that co-immunization of DNA vaccines with granulocyte-macrophage colony
      stimulating factor (GM-CSF) can increase immune responses. Here, experimental
      mice were immunized with HIV-1tat/pol/gag/env DNA vaccine with GM-CSF and boosted
      with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL
      4, IFN-gamma, IL-17 cytokines, total antibody, and IgG1 and IgG2a isotypes were
      assessed with ELISA. Results show that GM-CSF as adjuvant in DNA immunization
      significantly increased lymphocyte proliferation and IFN-gamma cytokines, but CTL
      response was tiny increased. Also GM-CSF as adjuvant decreased IL-4 cytokine vs
      mere vaccine group. IL-17 in the group that immunized with mixture of DNA
      vaccine/GM-CSF was significantly increased vs DNA vaccine group. Result of total
      antibody shows that GM-CSF increased antibody response in which both IgG1 and
      IgG2a increased. Overall, results confirmed the beneficial effect of GM-CSF as
      adjuvant to increase vaccine immunogenicity. The hallmark result of this study
      was to increase IL-17 cytokine with DNA vaccine/GM-CSF immunized group. This
      study for the first time provides the evidence of the potency of GM-CSF in the
      induction of IL-17 in response to a vaccine, which is important for control of
      infection such as HIV-1.

PMID- 28493368
TI  - Microbial nitrous oxide emissions in dryland ecosystems: mechanisms, microbiome
      and mitigation.
AB  - Globally, drylands represent the largest terrestrial biome and are projected to
      expand by 23% by the end of this century. Drylands are characterized by extremely
      low levels of water and nutrients and exhibit highly heterogeneous distribution
      in plants and biocrusts which make microbial processes shaping the dryland
      functioning rather unique compared with other terrestrial ecosystems. Nitrous
      oxide (N2 O) is a powerful greenhouse gas with ozone depletion potential. Despite
      of the pivotal influences of microbial communities on the production and
      consumption of N2 O, we have limited knowledge of the biological pathways and
      mechanisms underpinning N2 O emissions from drylands, which are estimated to
      account for 30% of total gaseous nitrogen emissions on Earth. In this article, we
      describe the key microbial players and biological pathways regulating dryland N2
      O emissions, and discuss how these processes will respond to emerging global
      changes such as climate warming, extreme weather events and nitrogen deposition.
      We also provide a conceptual framework to precisely manipulate the dryland
      microbiome to mitigate N2 O emissions in situ using emerging technologies with
      great specificity and efficacy. These cross-disciplinary efforts will enable the
      development of novel and environmental-friendly microbiome-based solutions to
      future mitigation strategies of climate change.

PMID- 28493369
TI  - Efficacy and safety of secukinumab in Taiwanese patients with moderate to severe
      plaque psoriasis: Subanalysis from ERASURE phase III study.
AB  - The efficacy and safety of secukinumab, a fully human anti-interleukin-17A
      monoclonal antibody, has been evaluated for moderate to severe plaque psoriasis
      in global trials which have included a low proportion of Asian subjects. We
      analyzed the efficacy and safety of secukinumab in Taiwanese patients in a phase
      III global clinical trial (ERASURE). Fifty-one Taiwanese patients were randomized
      into s.c. placebo, 150 and 300 mg secukinumab treatment groups. The proportions
      of patients who achieved 75% or more improvement in Psoriasis Area and Severity
      Index (PASI-75) at week 12 were 87.5% with 300 mg secukinumab, 70% with 150 mg
      secukinumab, 0% with placebo. Of the patients receiving 300 mg secukinumab, 68.8%
      achieved PASI-90 at week 12. Analysis of overall patients receiving 300 mg
      secukinumab for 12 weeks showed that the proportion of PASI-75 responders was
      less in patients with body mass index of 25 or more than less than 25. During the
      entire 52 weeks, the incidence of adverse events (AE) was consistent with the
      overall population in ERASURE. The most common AE (cases/per 100 patient-year)
      during the entire treatment period were upper respiratory tract infection and
      pruritus. The duration of upper respiratory tract infection per 100 patient-year
      was approximately 399 days in placebo, 1261 days in 150 mg secukinumab and 1805
      days in 300 mg secukinumab. The safety and efficacy of secukinumab in Taiwanese
      patients was compatible with the global phase III study in the treatment of
      moderate to severe plaque psoriasis.

PMID- 28493370
TI  - Guided left ventricular lead placement for cardiac resynchronization therapy - an
      opportunity for image integration: reply.

PMID- 28493371
TI  - Effects of repetitive transcranial magnetic stimulation on improvement of
      cognition in elderly patients with cognitive impairment: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: This systematic review and meta-analysis aimed to examine the effects
      of repetitive transcranial magnetic stimulation (rTMS) on cognitive function in
      older patients with cognitive impairment. METHODS: A literature search was
      performed for articles published in English using the 10 databases (MEDLINE,
      EMBASE, PsycINFO, INSPEC, the Cumulative Index to Nursing and Allied Health
      Literature Plus, AMED, Biological Sciences, ClinicalTrials.gov, the Cochrane
      Central Register of Controlled Trials and the Cochrane Database of Systematic
      Reviews) from their inception to May 2016. The primary outcome was cognitive
      function as measured by the Mini-Mental State Examination or the Alzheimer's
      Disease Assessment Scale-cognitive subscale. RESULTS: Seven RCTs were included in
      the meta-analysis, with a sample of 107 active and 87 sham rTMS. Active rTMS was
      found to be more effective in improving cognition (Hedges' g = 0.48; 95%
      confidence interval 0.12 to 0.84). CONCLUSIONS: High-frequency rTMS showed a
      benefit on cognition amongst older patients with mild to moderate Alzheimer's
      disease. rTMS was shown to have great potential as a safe and well-tolerated
      alternative intervention for cognition. Copyright (c) 2017 John Wiley & Sons,
      Ltd.

PMID- 28493372
TI  - Glycosuria and hyperglycemia in the neonatal period as the first clinical sign of
      Fanconi-Bickel syndrome.
AB  - Fanconi-Bickel syndrome is a rare inherited disease characterized by the
      combination of hepatorenal glycogen accumulation, proximal renal tubular
      dysfunction and impaired utilization of glucose and galactose. The first symptoms
      of the disorder are recognized in late infancy as clinical characteristics
      appear. Therapeutic approach is mainly conservative with supplements of calcium,
      phosphate and vitamin D and small frequent feedings to avoid hypoglycemia. We
      report 1 clinical case of very early diagnosis, a 19 days old baby girl, in which
      the first clinical sign of the disease was the detection of glycosuria and
      vomits. Serum alkaline phosphatase levels were very high without rickets. The
      patient presented postprandial hyperglycemia and fasting hypoglycemia. A complete
      24-hour glucose profile was obtained using a continuous glucose monitoring system
      in real time, which was fundamental not only for the diagnosis but also for the
      prevention of hypoglycemia. She received frequent small meals, galactose-free
      milk diet, and oral intakes of calcium, phosphorum, bicarbonate and vitamin D
      supplements with good evolution and normal height and weight gain.

PMID- 28493373
TI  - The novel alphaB-crystallin (CRYAB) mutation p.D109G causes restrictive
      cardiomyopathy.
AB  - Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by
      diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not
      completely known. We identified by a next-generation sequencing panel the novel
      CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in
      combination with skeletal myopathy with an early onset of the disease. CRYAB
      encodes alphaB-crystallin, a member of the small heat shock protein family, which
      is highly expressed in cardiac and skeletal muscle. In addition to in silico
      prediction analysis, our structural analysis of explanted myocardial tissue of a
      mutation carrier as well as in vitro cell transfection experiments revealed
      abnormal protein aggregation of mutant alphaB-crystallin and desmin, supporting
      the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be
      a novel RCM gene, which might have relevance for the molecular diagnosis and the
      genetic counseling of further affected families in the future.

PMID- 28493374
TI  - Polyphenols and Their Role in Obesity Management: A Systematic Review of
      Randomized Clinical Trials.
AB  - Polyphenols have been suggested to reduce body weight and modify body composition
      through different mechanisms. These effects have been extensively studied in
      animals and in vitro and to a lesser extent in humans. The aim of this review is
      to consider the association between polyphenols and body weight status by
      focusing on human intervention studies. We conducted a systematic literature
      search in MEDLINE (via EBSCOhost), ProQuest CENTRAL, and Cochrane CENTRAL without
      time restrictions. Randomized controlled trials assessing the effect of
      polyphenols on weight and/or body composition in the overweight and/or obese
      population were included. Nineteen studies met our inclusion criteria. Results
      suggest that further research is required before supporting a potential role of
      polyphenols in reducing weight in overweight and obese individuals (nine studies
      showed a significant decrease in weight by a mean of 1.47 +/- 0.58 kg).
      Nevertheless, several studies indicated that polyphenols might be effective in
      preventing small increases in weight during periods of overfeeding rather than
      reducing weight as such. The outcomes noted do not yet support polyphenol
      supplementation as a complementary approach in weight loss diets. Further larger
      trials with a duration of 12 months or more are needed to elucidate the effect of
      polyphenols on body weight status. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28493375
TI  - A systematic review of the psychological impact of false-positive colorectal
      cancer screening: What is the role of the general practitioner?
AB  - Screening for colorectal cancer (CRC) has both advantages (e.g. reduction in
      morbidity and mortality) and disadvantages (e.g. false positives and distress). A
      systematic review was therefore performed to improve our understanding of how
      false-positive CRC screening results affect patients psychologically (and to make
      recommendations for primary care). The PubMed, Embase, PsychINFO, CINAHL and
      Cochrane databases were searched in October 2014 and supplemented in December
      2016 to identify studies on the psychological impact of false-positive CRC
      screening. Original studies were eligible when they assessed psychological impact
      in a screening setting, provided they also included false-positive CRC screening
      results. Two authors independently assessed 2,367 available manuscripts and
      included seven. Heterogeneity in their outcome measures meant that data could not
      be pooled. Two studies showed that a false-positive CRC screening result caused
      some moderate psychological distress shortly before and after colonoscopy. The
      remaining five studies illustrated that the psychological distress of patients
      with true-positive and false-positive CRC screening results was comparable. We
      conclude that a false-positive CRC screening result may cause some moderate
      psychological distress, especially just before or after colonoscopy. We recommend
      that general practitioners mention this when discussing CRC screening with
      patients and monitor those with a false-positive outcome for psychological
      distress.

PMID- 28493376
TI  - Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African
      American patients with hypertension.
AB  - The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African
      American patients with hypertension in a 6-week, double-blind, randomized,
      placebo-controlled trial, for which the primary end point was change from
      baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients,
      with a mean age of 52 years, 57% women, and baseline 24-hour BP of 146/91 mm Hg.
      Treatment differences in 24-hour systolic BP between AZL-M 40 mg and placebo (
      5.0 mm Hg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80 mg and placebo (
      7.8 mm Hg; 95% confidence interval, -10.7 to -4.9) were significant (P<=.001 vs
      placebo for both comparisons). Changes in the clinic BPs were similar to the
      ambulatory BP results. Incidence rates of adverse events were comparable among
      the treatment groups, including those of a serious nature. In African-American
      patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs
      in a dose-dependent manner and was well tolerated.

PMID- 28493377
TI  - Neonatal myeloid derived suppressor cells show reduced apoptosis and
      immunosuppressive activity upon infection with Escherichia coli.
AB  - Susceptibility to infection during the neonatal period and reduced control of
      inflammation in neonates are attributed to immunosuppression persisting from
      fetal life. Myeloid-derived suppressor cells (MDSCs) are immature myeloid
      progenitors with suppressive activity and increased numbers in cord blood. We
      hypothesized that MDSCs contribute to innate host defence in neonates, paralleled
      by anti-inflammatory signalling.Phagocytic activity, infection induced apoptosis,
      expression of B-cell lymphoma (Bcl)-2 family proteins, production of reactive
      oxygen species (ROS), cytokine production and T-cell suppression of neonatal
      granulocytic-MDSCs (G-MDSCs) after infection with Escherichia coli (E. coli) were
      compared to neonatal autologous mature polymorphonuclear leukocytes (PMNs).
      Phagocytic activity of G-MDSCs upon infection with E. coli was equal to that of
      mature PMNs, however, apoptosis of G-MDSCs was decreased. G-MDSCs showed enhanced
      Bcl-2-expression and lower ROS production compared to PMNs. Inhibition of Bcl-2
      reduced apoptosis rates of G-MDSCs to that of mature PMNs. Induction of anti
      inflammatory transforming growth factor beta (TGF-beta) was enhanced, while pro
      inflammatory IL-8 decreased in G-MDSCs compared to PMNs. Infected G-MDSCs
      strongly suppressed proliferation of T cells. We show a direct role of G-MDSCs
      for anti-bacterial host defence. Prolonged survival and anti-inflammatory
      capacity suggest that G-MDSCs are important for immune-regulation after bacterial
      infection.

PMID- 28493378
TI  - Blood pressure control and cardiovascular risk in hypertensive patients with type
      2 diabetes: The German T2Target registry.
AB  - Blood pressure control in patients with type 2 diabetes and hypertension is poor.
      It is unclear how effectively general practitioners assess and treat such
      patients. T2Target included hypertensive patients with type 2 diabetes mellitus
      who had undergone ambulatory blood pressure monitoring within the past 3 months.
      Recordings were analyzed by the general practitioner and an independent center
      and the conclusions were compared. Nighttime hypertension was reported less
      frequently by the general practitioner in comparison with central assessment
      (43.9% vs 77.9%, P<.001), as were masked (4.0% vs 13.1%, P<.001) and isolated
      office (4.4% vs 8.8%, P<.001) hypertension. A total of 13.9% of patients were
      deemed to have controlled blood pressure (ambulatory blood pressure monitoring).
      For the 784 patients with uncontrolled blood pressure, 40.7% underwent no change
      to their antihypertensive treatment. Cardiovascular risk was underestimated, with
      11.1% deemed to be at very high risk, in contrast to the 97.0% of patients by
      central assessment. In conclusion, blood pressure control in hypertensive
      patients with type 2 diabetes mellitus is poor and not accurately assessed by
      office-based general practitioners, despite the use of ambulatory blood pressure
      monitoring.

PMID- 28493379
TI  - A highly selective fluorescent chemosensor for Cu2+ : synthesis and properties of
      a rhodamine B-containing diarylethene.
AB  - A diarylethene bearing a triazole-linked rhodamine B unit was synthesized. Its
      fluorescent emission was significantly enhanced in the presence of protons or
      Cu2+ due to transformation from the pirocyclic form to open-ring form. The
      fluorescence was quenched sequentially upon irradiation with 297 nm light based
      on the intramolecular fluorescence resonance energy transfer mechanism. In an
      acetonitrile: water binary solvent (1: 1 v/v), the compound showed significant
      fluorescent enhancement for Cu2+ compared with a wide range of tested metal ions
      with a fast response and a limit of detection of 2.86 * 10-8  mol L-1 . Using
      Cu2+ and UV light as the chemical inputs, and fluorescence intensity at 597 nm as
      the output, a logic gate was developed at the molecular level. Moreover, the
      compound can be used with a high accuracy to detect Cu2+ in a natural water
      sample.

PMID- 28493380
TI  - Post-Synthesis Amine Borane Functionalization of a Metal-Organic Framework and
      Its Unusual Chemical Hydrogen Release Phenomenon.
AB  - A novel strategy for post-synthesis amine borane functionalization of MOFs under
      gas-solid phase transformation, utilizing gaseous diborane, is reported. The
      covalently confined amine borane derivative decorated on the framework backbone
      is stable when preserved at low temperature, but spontaneously liberates soft
      chemical hydrogen at room temperature, leading to the development of an unusual
      borenium type species (-NH=BH2+ ) ion-paired with a hydroborate anion.
      Furthermore, the unsaturated amino borane (-NH=BH2 ) and the MU-iminodiborane (
      MU-NHB2 H5 ) were detected as final products. A combination of DFT based
      molecular dynamics simulations and solid state NMR spectroscopy, utilizing
      isotopically enriched materials, were undertaken to unequivocally elucidate the
      mechanistic pathways for H2 liberation.

PMID- 28493381
TI  - Nitrogen-Doped Graphitic Porous Carbon Nanosheets Derived from In Situ Formed g
      C3 N4 Templates for the Oxygen Reduction Reaction.
AB  - Heteroatom-doped carbon materials have been considered as potential substitutes
      for Pt-based electrocatalysts for the oxygen reduction reaction (ORR) in alkaline
      fuel cells. Here we report the synthesis of oxygen-containing nitrogen-doped
      carbon (ONC) nanosheets through the carbonization of a mixture that contained
      glucose and dicyandiamide (DCDA). In situ formed graphitic carbon nitride (g-C3
      N4 ) derived from DCDA provided a nitrogen-rich template, thereby facilitating
      the formation of ONC nanosheets. The resultant ONC materials with high nitrogen
      content, high specific surface areas, and highly mesoporous total volume
      displayed excellent electrochemical performance, including a similar ORR onset
      potential, half-potential, a higher diffusion-limited current, and excellent
      tolerance to methanol than that of the commercial Pt/C catalyst, respectively.
      Moreover, the ONC-850 nanosheet displayed high long-term durability even after
      1000 cycles as well as a high electron transfer number of 3.92 (4.0 for Pt/C).
      Additionally, this work provides deeper insight into these materials and a
      versatile strategy for the synthesis of cost-effective 2D N-doped carbon
      electrocatalysts.

PMID- 28493382
TI  - Thiomaleimide Functionalization for Selective Biological Fluorescence Detection
      of Peroxynitrite as Tested in HeLa and RAW 264.7 Cells.
AB  - The role of fluorescent molecules in diagnosis, treatment as well as in
      biomedical research has great current medicinal significance and is the focus of
      concentrated effort across the scientific research spectrum. Related research
      continues to reveal new practical sensing systems that bear enhanced features for
      interfacing of substituted molecules with biological systems. As part of an
      effort to better understand chalcogenide systems, a new dithiomaleimide BODIPY
      (BDP-NGM) probe has been designed, synthesized and characterized. The
      fluorescence of BDP-NGM was quenched by the incorporation of [3,4
      bis(phenylthio)] on the maleimide-4-phenyl moiety which is, in turn, placed at
      the meso-position of the BODIPY system. The probe shows a turn-on fluorescence
      response upon reaction with ONOO- ; mass spectral evidence reveals peaks in
      agreement with products involving oxidation of the sulfur groups to sulfone
      groups. An about 18.0-fold emission intensity enhancement was found. By
      comparison, the emission signal from another ROS/RNS, superoxide, gave a modest
      turn on signal (~5.0-fold). The reaction is complete within 10 min, judging from
      the monitoring of the turn-on fluorescence process; the detection limit was found
      to be 0.4 MUm. BDP-NGM can be used for the detection of ONOO- under both acidic
      and basic conditions. Live cell imaging showed that the current probe can be used
      for the selective detection of ONOO- in living systems.

PMID- 28493383
TI  - A large-scale assessment of temporal trends in meta-analyses using systematic
      review reports from the Cochrane Library.
AB  - INTRODUCTION: Previous studies suggest that many systematic reviews contain meta
      analyses that display temporal trends, such as the first study's result being
      more extreme than later studies' or a drift in the pooled estimate. We assessed
      the extent and characteristics of temporal trends using all Cochrane intervention
      reports published 2008-2012. METHODS: We selected the largest meta-analysis
      within each report and analysed trends using methods including a Z-test (first
      versus subsequent estimates); generalised least squares; and cumulative sum
      charts. Predictors considered include meta-analysis size and review group.
      RESULTS: Of 1288 meta-analyses containing at least 4 studies, the point estimate
      from the first study was more extreme and in the same direction as the pooled
      estimate in 738 (57%), with a statistically significant difference (first versus
      subsequent) in 165 (13%). Generalised least squares indicated trends in 717
      (56%); 18% of fixed effects analyses had at least one violation of cumulative sum
      limits. For some methods, meta-analysis size was associated with temporal
      patterns and use of a random effects model, but there was no consistent
      association with review group. CONCLUSIONS: All results suggest that more meta
      analyses demonstrate temporal patterns than would be expected by chance. Hence,
      assuming the standard meta-analysis model without temporal trend is sometimes
      inappropriate. Factors associated with trends are likely to be context specific.

PMID- 28493384
TI  - Risk factors for single crowns supported by short (6-mm) implants in the
      posterior region: A prospective clinical and radiographic study.
AB  - BACKGROUND: The use of short implants is still not a consensus for challenging
      clinical situations, such as unfavorable crown-to-implant (C/I) ratio. PURPOSE:
      This prospective study evaluated the rates of prosthetic complications and
      implant failure, the mean marginal bone loss of 6-mm dental implants with single
      crowns in posterior regions and the potential risk factors. MATERIALS AND
      METHODS: Forty-six dental implants, 6-mm long and 4.1-mm wide, were placed in the
      posterior region in 20 patients. Patients were clinically and radiographically
      examined after the restoration with single crowns and on a yearly basis.
      Potential risk factors (arch, bruxism, maximum bite force, anatomical and
      clinical C/I ratios, and occlusal table area) were analyzed according to the
      following outcomes: implant survival, bone loss, and prosthetic complications.
      RESULTS: The mean follow-up time was 45 +/- 9 (16-57) months. There was no early
      loss of implants. After prosthetic loading, 4 implants were lost (2 in the
      mandible and 2 in the maxilla; 91.3% survival), and there were 13 prosthetic
      complications (28.3%), yielding a 65.2% success rate. The frailty term showed a
      95% greater chance of loss in the mandible than the maxilla. Mean peri-implant
      bone loss was of 0.2 +/- 0.4 mm, 0.1 +/- 0.2 mm, 0.1 +/- 0.3 mm, and 0.2 +/- 0.4
      mm in the first, second, third, and fourth years, respectively, with a mean
      cumulative loss of 0.3 +/- 0.5 mm at 48 months. In the multilevel model, the
      effects of the clinical C/I ratio and time were significant for bone loss (P <
      .001). It was estimated that a mean bone loss of 0.1 mm is associated with both a
      one-unit increase in time (12 months) and a 0.1 increase in the clinical C/I
      ratio. The other potential risk factors showed no significant relationship with
      the outcomes. CONCLUSIONS: The 6-mm implants supporting single crowns performed
      well, but the mandible shows a higher risk of failure. The time and clinical C/I
      ratio are predictors for bone loss.

PMID- 28493385
TI  - Effects of 25-hydroxycholecalciferol with two D3 vitamin levels on production and
      immunity parameters in broiler chickens.
AB  - This study was performed in Ross 308 chickens aged 1-21 days and aimed to
      evaluate whether the addition of 25-hydroxycholecalciferol (25(OH)D3 ) to broiler
      chicken diets affects their growth performance and immunity. A completely random
      2 * 2 factorial arrangement was used with two levels of vitamin D3 and the
      absence or presence of 25(OH)D3 , corresponding to four treatments based on
      sorghum + soya bean diets: (i) 200 IU of vitamin D3 /kg of feed (Diet 1) (NRC, ),
      (ii) Diet 1 + 69 MUg of 25(OH)D3 /kg of feed (Diet 2), (iii) 5,000 IU of vitamin
      D3 /kg of feed (Diet 3) and (iv) Diet 3 + 69 MUg of 25(OH)D3 /kg of feed (Diet
      4). Each treatment was conducted with six replicates of 10 chickens each. Water
      and feed was supplied ad libitum. The results showed significantly increased
      growth and tibia ash (p < .05) in the birds fed 5,000, IU of vitamin D3 /kg +
      25(OH)D3 . Additionally, the cellular immune response increased significantly (p
      < .05) in both treatments with added 25(OH)D3. Based on the results obtained
      under the current test conditions, the addition of 25(OH)D3 at a rate of 69
      MUg/kg to diets containing vitamin D3 improved the cellular immune response and
      mineral deposition in the bones of broilers aged 1-21 days. Because these
      parameters are very important in modern poultry farming, these results indicate
      that supplementation with 25(OH)D3 should improve broiler production.

PMID- 28493386
TI  - A Ferroelectric Ceramic/Polymer Composite-Based Capacitive Electrode Array for In
      Vivo Recordings.
AB  - A new implantable capacitive electrode array for electrocorticography signal
      recording is developed with ferroelectric ceramic/polymer composite. This
      ultrathin and electrically safe capacitive electrode array is capable of
      attaching to the biological tissue conformably. The barium titanate/polyimide
      (BaTiO3 /PI) nanocomposite with high dielectric constant is successfully
      synthesized and employed as the ultrathin dielectric layer of the capacitive
      BaTiO3 /PI electrode array. The performance of the capacitive BaTiO3 /PI
      electrode array is evaluated by electrical characterization and 3D finite-element
      modeling. In vivo, neural experiments on the visual cortex of rats show the
      reliability of the capacitive BaTiO3 /PI electrode array. This work shows the
      potentials of capacitive BaTiO3 /PI electrode array in the field of
      brain/computer interfaces.

PMID- 28493387
TI  - Current Advances in Highly Multiplexed Antibody-Based Single-Cell Proteomic
      Measurements.
AB  - Single-cell measurements have played a critical role in revealing the complex
      signaling dynamics and heterogeneity present in cells, but there is still much to
      learn. Measuring samples from bulk populations of cells often masks the
      information and dynamics present in subsets of cells. Common single-cell protein
      studies rely on fluorescent microscopy and flow cytometry but are limited in
      multiplexing ability owing to spectral overlap. Recently, technology advancements
      in single-cell proteomics have allowed highly multiplexed measurement of multiple
      parameters simultaneously by using barcoded microfluidic enzyme-linked
      immunosorbent assays and mass cytometry techniques. In this review, we will
      describe recent work around multiparameter single-cell protein measurements and
      critically analyze the techniques.

PMID- 28493389
TI  - Contemporary transcatheter aortic valve replacement with third-generation balloon
      expandable versus self-expanding devices.
AB  - OBJECTIVES: To evaluate balloon-expandable and self-expanding third-generation
      transcatheter aortic valve replacement (TAVR) devices according to patient
      selection criteria and outcomes. BACKGROUND: Two competing third-generation TAVR
      technologies are currently commercially available in the US. There are no
      published head-to-head comparisons of the relative performance of these two
      devices. METHODS: 257 consecutive patients undergoing TAVR with a third
      generation balloon-expandable (Edwards Sapien 3) or self-expanding device
      (Medtronic CoreValve Evolut R) at a single US medical center were included.
      Choice of TAVR device was at the discretion of the multidisciplinary Heart Team.
      Baseline clinical characteristics, echocardiographic and CT imaging, procedural
      and 30-day outcomes were prospectively collected. RESULTS: 74 patients received a
      self-expanding valve (SEV) and 183 received a balloon-expandable valve (BEV).
      Patients selected for SEV were more frequently women, with lower body surface
      area and smaller calcified iliofemoral arteries. Three SEV patients required
      implantation of a second valve to successfully treat paravalvular leak. Only one
      BEV patient had moderate paravalvular regurgitation. There was no difference in
      the rate of stroke, major vascular complication or bleeding. Permanent pacemaker
      implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and
      hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30-day
      mortality was comparable (1.4% vs 1.6%, P = 1.00). CONCLUSIONS: Short-term
      outcomes were equivalent between the two technologies. Clinically significant
      paravalvular regurgitation was rare. SEV were more frequently selected in women
      and patients with challenging transfemoral access, but were associated with
      higher permanent pacemaker implantation rate and longer hospital length of stay.

PMID- 28493388
TI  - Magnetic resonance elastography measured shear stiffness as a biomarker of
      fibrosis in pediatric nonalcoholic fatty liver disease.
AB  - : Magnetic resonance elastography (MRE) is a promising technique for noninvasive
      assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty
      liver disease (NAFLD). However, data in children are limited. The purpose of this
      study was to determine the accuracy of MRE for the detection of fibrosis and
      advanced fibrosis in children with NAFLD and to assess agreement between manual
      and novel automated reading methods. We performed a prospective, multicenter
      study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were
      analyzed manually at two reading centers, and using a new automated technique.
      Analysis using each approach was done independently. Correlations were determined
      between MRE analysis methods and fibrosis stage. Thresholds for classifying the
      presence of fibrosis and of advanced fibrosis were computed and cross-validated.
      In 90 children with a mean age of 13.1 +/- 2.4 years, median hepatic stiffness
      was 2.35 kPa. Stiffness values derived by each reading center were strongly
      correlated with each other (r = 0.83). All three analyses were significantly
      correlated with fibrosis stage (center 1, rho = 0.53; center 2, rho = 0.55; and
      automated analysis, rho = 0.52; P < 0.001). Overall cross-validated accuracy for
      detecting any fibrosis was 72.2% for all methods (95% confidence interval [CI],
      61.8%-81.1%). Overall cross-validated accuracy for assessing advanced fibrosis
      was 88.9% (95% CI, 80.5%-94.5%) for center 1, 90.0% (95% CI, 81.9%-95.3%) for
      center 2, and 86.7% (95% CI, 77.9%-92.9%) for automated analysis. CONCLUSION: 2D
      MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and
      validation of automated analysis techniques will be an important step in
      standardizing MRE. How to best integrate MRE into clinical protocols for the
      assessment of NAFLD in children will require prospective evaluation. (Hepatology
      2017;66:1474-1485).

PMID- 28493390
TI  - Discrimination of a nerve fiber that is the origin of a cauda equina tumor using
      acetylcholinesterase staining.
AB  - Spinal nerve sheath tumors are well known to typically originate from dorsal
      sensory nerve roots. However, it is difficult to anatomically identify the origin
      in the case of cauda equina tumors. In this study, we aimed to ascertain whether
      a cauda equina nerve root removed with a nerve sheath tumor was a motor nerve
      using acetylcholinesterase (AchE) staining. Nerve rootlet sections removed with
      tumors were stained for AchE using the AchE Rapid Staining Kit. Additionally, we
      performed intraoperative motor-evoked potential (MEP) monitoring following either
      transcranial electrical stimulation (TES) or electrical stimulation of nerve
      rootlets. The muscular strength of the lower extremities was assessed bilaterally
      before and after surgery using manual muscle testing. An AchE-positive motor
      nerve rootlet that was the origin of a cauda equina tumor was observed in one of
      the 12 patients. In this patient, a MEP in the right quadriceps evoked by
      electrical stimulation of this rootlet was detected. TES-MEP showed a 30%
      decrease in the amplitude in the right quadriceps evoked after tumor resection
      with this nerve rootlet. However, the motor strength in both lower extremities
      did not change after surgery. AchE staining and intraoperative MEP monitoring
      could detect the motor nerve rootlet that was the origin of a cauda equina tumor.
      Nerve sheath tumors originating from the motor nerve might be rare even in cauda
      equina.

PMID- 28493391
TI  - Haplotype reference consortium panel: Practical implications of imputations with
      large reference panels.
AB  - Recently, the Haplotype Reference Consortium (HRC) released a large imputation
      panel that allows more accurate imputation of genetic variants. In this study, we
      compared a set of directly assayed common and rare variants from an exome array
      to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed
      that imputation using the HRC panel improved the concordance between assayed and
      imputed genotypes at common, and especially, low-frequency variants. Furthermore,
      we performed a genome-wide association meta-analysis of vertical cup-disc ratio,
      a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and
      HRC imputations. We compared the results of the meta-analysis using 1000GP to the
      meta-analysis results using HRC. Overall, we found that using HRC imputation
      significantly improved P values (P = 3.07 * 10-61 ), particularly for suggestive
      variants. Both meta-analyses were performed in the same sample size, yet we found
      eight genome-wide significant loci in the HRC-based meta-analysis versus seven
      genome-wide significant loci in the 1000GP-based meta-analysis. This study
      provides supporting evidence of the new avenues for gene discovery and fine
      mapping that the HRC imputation panel offers.

PMID- 28493392
TI  - Interventricular septal hematoma following repair of a ventricular septal defect.
AB  - An interventricular septal hematoma is a rare complication after patch closure of
      a ventricular septal defect (VSD). We describe three cases of interventricular
      septal hematomas following patch VSD and discuss their management.

PMID- 28493393
TI  - Final results of a European, multi-centre, prospective, observational Study of
      PermacolTM collagen paste injection for the treatment of anal fistula.
AB  - AIM: PermacolTM collagen paste (PermacolTM paste) is an acellular cross-linked
      porcine dermal collagen matrix suspension for use in soft tissue repair. The use
      of PermacolTM paste in the filling of anorectal fistula tract is a new sphincter
      preserving method for fistula repair. The MASERATI100 study was a prospective,
      observational clinical study with the objective to assess the efficacy of
      PermacolTM collagen paste for anal fistula repair in 100 patients. METHOD:
      Patients (N=100) with anal fistula were treated at ten European surgical sites
      with a sphincter-preserving technique using PermacolTM paste. Fistula healing was
      assessed at 1, 3, 6, and 12 months post-treatment, with the primary endpoint
      being healing at 6 months. Faecal continence and patient satisfaction were
      surveyed at each follow-up; adverse events (AEs) were monitored throughout the
      follow-up. RESULTS: At 6 months post-surgery, 56.7% of patients were healed, and
      the percentage healed was largely maintained, with 53.5% healed at 12 months.
      29.0% of patients had at least one AE, and 16.0% of patients had one or more
      procedure-related AE. Most AEs reported were minor and similar to those commonly
      observed after fistula treatment, and the incidence of serious adverse events was
      low (4.0% of patients). Regardless of treatment outcome, 73.0% of patients were
      satisfied or very satisfied with the procedure. CONCLUSION: PermacolTM paste
      provides a promising sphincter-preserving treatment for anal fistulas with
      minimal adverse side-effects. This article is protected by copyright. All rights
      reserved.

PMID- 28493394
TI  - Determination of effective charges and ionic mobilities of polycationic
      antimicrobial peptides by capillary isotachophoresis and capillary zone
      electrophoresis.
AB  - Capillary ITP (CITP) and CZE were applied to the determination of effective
      charges and ionic mobilities of polycationic antimicrobial peptides (AMPs).
      Twelve AMPs (deca- to hexadecapeptides) containing three to seven basic amino
      acid residues (His, Lys, Arg) at variable positions of peptide chain were
      investigated. Effective charges of the AMPs were determined from the lengths of
      their ITP zones, ionic mobilities, and molar concentrations, and from the same
      parameters of the reference compounds. Lengths of the ITP zones of AMPs and
      reference compounds were obtained from their CITP analyses in cationic mode using
      leading electrolyte (LE) composed of 10 mM NH4 OH, 40 mM AcOH (acetic acid), pH
      4.1, and terminating electrolyte (TE) containing 40 mM AcOH, pH 3.2. Ionic
      mobilities of AMPs and singly charged reference compounds (ammediol or arginine)
      were determined by their CZE analyses in the BGE of the same composition as the
      LE. The effective charges numbers of AMPs were found to be in the range 1.65
      5.04, i.e. significantly reduced as compared to the theoretical charge numbers
      (2.86-6.99) calculated from the acidity constants of the analyzed AMPs. This
      reduction of effective charge due to tightly bound acetate counterions
      (counterion condensation) was in the range 17-47% depending on the number and
      type of the basic amino acid residues in the AMPs molecules. Ionic mobilities of
      AMPs achieved values (26.5-38.6) * 10-9  m2 V-1 s-1 and in most cases were in a
      good agreement with the ratio of their effective charges and relative molecular
      masses.

PMID- 28493396
TI  - Species sorting and stoichiometric plasticity control community C:P ratio of
      first-order aquatic consumers.
AB  - Ecological stoichiometry has proven to be invaluable for understanding consumer
      response to changes in resource quality. Although interactions between trophic
      levels occur at the community level, most studies focus on single consumer
      species. In contrast to individual species, communities may deal with trophic
      mismatch not only through elemental plasticity but also through changes in
      species composition. Here, we show that a community of first-order consumers
      (e.g. zooplankton) is able to adjust its stoichiometry (C:P) in response to
      experimentally induced changes in resource quality, but only to a limited extent.
      Furthermore, using the Price equation framework we show the importance of both
      elemental plasticity and species sorting. These results illustrate the need for a
      community perspective in ecological stoichiometry, requiring consideration of
      species-specific elemental composition, intraspecific elemental plasticity and
      species turnover.

PMID- 28493398
TI  - Peer facilitation and burnout: the READ-SG pilot.
AB  - BACKGROUND: Although there is much research about the prevalence of burnout among
      doctors and postgraduate doctor trainees, there is a paucity of evidence for
      effective preventive measures. METHODS: First-year postgraduate doctor trainees
      (PGY1s) in Internal Medicine at our institution were given protected time to
      participate in peer-facilitated monthly small group discussions on topics
      regarding humanism and professional development. The authors prompted
      participants before each session and followed a novel reflect, empathise, analyse
      and discuss in small groups (READ-SG) format. During the pilot period the authors
      administered a survey, approved by the Institutional Review Board, asking
      participants to rank the perceived effect of the sessions on their professional
      development and various symptoms of burnout, including levels of empathy, stress
      and motivation. RESULTS: Out of 20 PGY1s available to attend each session over
      the 3-month pilot period, there were an average of 9.6 attendees per session,
      with a 100 per cent survey completion rate, yielding 29 surveys. A total of 21
      survey responses (72.4%) reported speaking during the sessions, and 29 (100%)
      reported that the sessions were important to have. Average scores on a Likert
      scale from 1 to 5 (ranging from negative to positive, respectively) for the
      perceived effect of the sessions on each measure were: 4.59 for professional
      development; 4.38 for empathy; 4.00 for stress; and 4.28 for motivation. There is
      a paucity of evidence for effective preventive measures [for burnout]
      CONCLUSIONS: Peer-facilitated monthly small group discussions using the READ-SG
      method seem to have positive effects on participants' sense of professional
      development and symptoms of burnout among postgraduate doctor trainees.

PMID- 28493397
TI  - A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma.
AB  - Ocular coloboma (OC) is a defect in optic fissure closure and is a common cause
      of severe congenital visual impairment. Bilateral OC is primarily genetically
      determined and shows marked locus heterogeneity. Whole-exome sequencing (WES) was
      used to analyze 12 trios (child affected with OC and both unaffected parents).
      This identified de novo mutations in 10 different genes in eight probands. Three
      of these genes encoded proteins associated with actin cytoskeleton dynamics:
      ACTG1, TWF1, and LCP1. Proband-only WES identified a second unrelated individual
      with isolated OC carrying the same ACTG1 allele, encoding p.(Pro70Leu). Both
      individuals have normal neurodevelopment with no extra-ocular signs of Baraitser
      Winter syndrome. We found this mutant protein to be incapable of incorporation
      into F-actin. The LCP1 and TWF1 variants each resulted in only minor disturbance
      of actin interactions, and no further plausibly causative variants were
      identified in these genes on resequencing 380 unrelated individuals with OC.

PMID- 28493399
TI  - Diagnosis of fatty liver by computed tomography coronary artery calcium score.
AB  - Nonalcoholic fatty liver disease may range from simple steatosis to fibrosis and
      cirrhosis. It is associated with the development of coronary artery calcification
      and appears to be an independent predictor of future adverse cardiovascular
      events. As the presence of a fatty liver appears to portray an independent
      increased risk, it may be beneficial to note this on coronary artery calcium
      scoring reports. Determination of fatty liver is relatively easy to perform. We
      discuss the method used by the Multi-Ethnic Study of Atherosclerosis (MESA) study
      for determination of fatty liver from CT coronary artery calcium scoring
      acquisitions, which may be implemented in clinical analysis.

PMID- 28493400
TI  - Technoference: Parent Distraction With Technology and Associations With Child
      Behavior Problems.
AB  - Heavy parent digital technology use has been associated with suboptimal parent
      child interactions, but no studies examine associations with child behavior. This
      study investigates whether parental problematic technology use is associated with
      technology-based interruptions in parent-child interactions, termed
      "technoference," and whether technoference is associated with child behavior
      problems. Parent reports from 170 U.S. families (child Mage  = 3.04 years) and
      actor-partner interdependence modeling showed that maternal and paternal
      problematic digital technology use predicted greater technoference in mother
      child and father-child interactions; then, maternal technoference predicted both
      mothers' and fathers' reports of child externalizing and internalizing behaviors.
      Results suggest that technological interruptions are associated with child
      problem behaviors, but directionality and transactional processes should be
      examined in future longitudinal studies.

PMID- 28493401
TI  - The effect of adjuvant chemotherapy on survival and recurrence after curative
      rectal cancer surgery in patients who are histologically node negative after
      neoadjuvant chemoradiotherapy.
AB  - AIM: The aim of this study was to evaluate whether adjuvant chemotherapy will
      affect recurrence rate or disease-free and overall survival in patients with
      rectal adenocarcinoma who were staged with MRI node-positive disease (mrN+)
      preoperatively. These patients underwent neoadjuvant chemoradiotherapy with
      curative rectal cancer surgery and their pathological staging was negative for
      nodal disease (ypN0). There is no consensus on the role of adjuvant chemotherapy
      in such patients. METHOD: Patients who received neoadjuvant chemoradiotherapy and
      underwent curative rectal cancer surgery for rectal adenocarcinoma staged as
      [mrTxN+M0] on MRI staging and who on pathological staging were found to be
      [ypTxN0M0] were retrospectively identified from January 2008 December 2012 from
      two tertiary referral centres (Royal Marsden Hospital, London and Saint-Andre
      Hospital, Bordeaux). RESULTS: One hundred and sixty-three patients were recruited
      and, after propensity matching at a ratio of 2:1, n = 80 patients were divided to
      receive adjuvant (n = 28) or no adjuvant treatment (n = 52). A comparison of
      adjuvant chemotherapy vs no adjuvant therapy showed that the mean overall
      survival was 2.67 vs 3.60 years (P = 0.42) and disease-free survival was 2.27 vs
      3.32 years (P = 0.14). CONCLUSION: This study found no significant difference in
      survival or disease recurrence between patients who received adjuvant
      chemotherapy and patients who did not. There is no clear evidence to support or
      dismiss the use of adjuvant chemotherapy for patients who were node positive on
      preoperative MRI and node negative on histopathological staging. Further
      multicentre prospective randomized trials are needed to identify the appropriate
      treatment regime for this group of patients.

PMID- 28493403
TI  - Suicide prevention in mental health services: A qualitative analysis of coroners'
      reports.
AB  - Suicide is a major concern for mental health nurses because of its clear
      correlation with mental illness. In New Zealand, coroners investigate all deaths
      that appear to be a result of suicide, and provide reports to mental health
      services (MHS). The aim of the present study was to investigate coronial
      recommendations to MHS in relation to suicide prevention and to examine clinical
      and family responses to these. The present study was a three-phase design: (i)
      analysis of coroners' recommendations related to suicide in MHS; (ii) interviews
      with clinicians for their response to the recommendations; and (iii) interviews
      with individuals working with families of consumers of MHS for their responses in
      relation to family-related recommendations. A qualitative content analysis was
      conducted on the recommendations from coroners, the interviews with clinical
      leaders, and the focus group for family workers. Coroners recommended that MHS
      should implement suicide-prevention strategies that would facilitate improved
      communication, risk containment, service delivery, and family involvement.
      Clinicians agreed with most recommendations, apart from those related to risk
      containment. Family workers endorsed the coronial perspective that family
      inclusion in MHS was suboptimal. Coroners, MHS, and mental health nurses need to
      consider the latest clinical evidence for suicide prevention. However, given the
      complexity of factors that influence suicide, it is important to be realistic
      about MHS role in preventing suicide, but ensure that MHS provide interventions
      for which there is evidence, including facilitating family participation and
      providing access to psychotherapies.

PMID- 28493402
TI  - Development and validation of HPLC-MS/MS method for the determination of
      lixivaptan in mouse plasma and its application in a pharmacokinetic study.
AB  - The aim of the present study was to develop a simple, sensitive and accurate
      liquid chromatography-electrospray ionization tandem mass spectrometry (ESI
      MS/MS) method for the determination of lixivaptan (LIX) in mouse plasma using
      vildagliptin as the internal standard (IS). A precipitation procedure was used
      for the extraction of LIX and vildagliptin from mouse plasma. Chromatographic
      separation of LIX was achieved using a C18 analytical column (50 * 2.1 mm, 1.8
      MUm) at 25 degrees C. The mobile phase comprised acetonitrile and ammonium
      formate (10 mm, pH 3.1; 40:60, v/v) pumped at a flow rate of 0.3 mL min-1 . A
      tandem mass spectrometer with an electrospray ionization source was used to
      perform the assay. Quantification of LIX at m/z 290 -> 137 and IS at 154 -> 97
      was attained through multiple reaction monitoring. The investigated method was
      authenticated following the bio-analytical method of validation guidelines of the
      US Food and Drug Administration. The developed method showed a good linearity
      over the concentration range from 5 to 500 ng mL-1 , and the calibration curve
      was linear (r = 0.9998). The mean recovery of LIX from mouse plasma was 99.2 +/-
      0.68%. All validation parameters for LIX were within the levels required for
      acceptance. The proposed method was effectively used for a pharmacokinetic study
      of LIX in mouse plasma.

PMID- 28493404
TI  - Accuracy of finite-difference harmonic frequencies in density functional theory.
AB  - Analytic Hessians are often viewed as essential for the calculation of accurate
      harmonic frequencies, but the implementation of analytic second derivatives is
      nontrivial and solution of the requisite coupled-perturbed equations engenders a
      sizable memory footprint for large systems, given that these equations are not
      required for energy and gradient calculations in density functional theory. Here,
      we benchmark the alternative approach to harmonic frequencies based on finite
      differences of analytic first derivatives, a procedure that is amenable to large
      scale parallelization. Not only for absolute frequencies but also for isotopic
      and conformer-dependent frequency shifts in flexible molecules, we find that the
      finite-difference approach exhibits mean errors < 0.1 cm-1 as compared to results
      based on an analytic Hessian. For very small frequencies corresponding to
      nonbonded vibrations in noncovalent complexes (for which the harmonic
      approximation is questionable anyway), the finite-difference error can be larger,
      but even in these cases the errors can be reduced below 0.1 cm-1 by judicious
      choice of the displacement step size and a higher-order finite-difference
      approach. The surprising accuracy and robustness of the finite-difference results
      suggests that availability of the analytic Hessian is not so important in today's
      era of commodity processors that are readily available in large numbers. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28493405
TI  - Australian urban Indigenous smokers' perspectives on nicotine products and
      tobacco harm reduction.
AB  - INTRODUCTION AND AIMS: Indigenous Australians experience a significant gap in
      life expectancy compared with non-Indigenous Australians. Indigenous communities
      have high-smoking prevalence and low engagement with cessation therapies. This
      qualitative research, conducted in an urban Australian Indigenous community,
      explored smokers' views on smoking, quitting and engagement with current nicotine
      replacement therapies. Opinions on acceptability of tobacco harm reduction were
      sought. We explored the acceptability of novel nicotine products, that is, new or
      unfamiliar products, including non-therapeutic options, such as e-cigarettes.
      DESIGN AND METHODS: Focus groups and individual interviews with adult Indigenous
      daily smokers (n = 27) were used. Current and novel nicotine products were
      displayed and demonstrated. Discussions were audio-recorded, transcribed and
      analysed thematically. RESULTS: Participants expressed interest in trying
      existing and novel nicotine products. Short-to-medium term use of nicotine
      replacement therapy for quitting was generally acceptable; views on long-term use
      were mixed. Interest in use of tobacco substitutes depended on their perceived
      effectiveness, providing a 'kick' and 'relieving stress'. Desirable qualities for
      tobacco substitutes were identified with gender differences and product
      preferences noted. The unpleasant taste of existing products is a barrier to both
      short-term and long-term use. DISCUSSION: We found substantial interest in trying
      some existing and novel nicotine products, mostly for short-term use. A number of
      attributes were identified that would make nicotine products potentially
      acceptable as a long-term substitute. CONCLUSIONS: Some participants were
      interested in long-term substitution if acceptable products were available.
      Improvements in current products and access to novel products are needed if
      tobacco harm reduction is to be acceptable. [Yuke K, Ford P, Foley W, Mutch A,
      Fitzgerald L, Gartner C. Australian urban Indigenous smokers' perspectives on
      nicotine products and tobacco harm reduction. Drug Alcohol Rev 2018;37:87-96].

PMID- 28493407
TI  - First-person perspective video to enhance simulation.
AB  - BACKGROUND: Simulation training is increasingly being used as part of the
      undergraduate medical curriculum, but it remains time and faculty member
      intensive. To improve efficacy, videos have been used prior to the simulation of
      practical procedures; however, using videos prior to simulation training
      concerning the management of patients who are unwell has not been investigated.
      The aim of this project was to see whether clinical decision-making and non
      technical skills can be improved if a video is used prior to simulation training,
      and uniquely to enhance the authenticity we filmed it using a first-person
      perspective. METHODOLOGY: We conducted a randomised controlled trial with 40
      final-year medical students randomised into two groups. One group viewed a video
      filmed in first person prior to a simulation scenario, whereas the other group
      did not view the video. The two groups then carried out the simulation and were
      assessed with 'time to' investigation and treatment decisions. Further
      quantitative data were collected for non-technical skills using the Ottawa Crisis
      Resource Management (OCRM) score. Qualitative data were collected from the
      students as to the perceived ease of use and helpfulness of the video. Simulation
      training is increasingly being used as part of the undergraduate medical
      curriculum RESULTS: The students who watched the video appeared to perform better
      in clinical decision-making and non-technical skills. The students were extremely
      receptive to the use of a first-person perspective video, and highlighted its
      perceived realism and its help as a memory aid. DISCUSSION: The use of this style
      of video was warmly received by students and opens the possibility of further use
      to enhance simulation training.

PMID- 28493408
TI  - Monoubiquitination joins polyubiquitination as an esteemed proteasomal targeting
      signal.
AB  - A polyubiquitin chain attached covalently to the target substrate has been
      recognized for long as the "canonical" proteasomal degradation signal. However,
      several proteins have been shown to be targeted for degradation following
      monoubiquitination, indicating that the proteasome can recognize signals other
      than a ubiquitin polymer. A comprehensive screen aiming at determining the extent
      of this mode of recognition revealed that ~40% of mammalian and ~20% of yeast
      proteins are degraded following monoubiquitination. Characterization of these
      proteins showed that on average, the monoubiquitinated proteins are smaller than
      the polyubiquitinated ones, and in humans, are less disordered. Further, proteins
      degraded by the two different modes belong to distinct functional groups. These
      findings along with detailed structural analysis of the proteasome, its ubiquitin
      receptors and deubiquitinating enzymes, suggest that the ubiquitin signal - its
      formation, recognition, editing, and removal - is far more complex and diverse
      than originally assumed. Also see the video abstract here:
      https://youtu.be/QKpN9c6Rg20.

PMID- 28493406
TI  - Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy
      and muscle-wasting conditions.
AB  - Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino
      acid leucine that has been reported to have anabolic effects on protein
      metabolism. The aims of this article were to summarize the results of studies of
      the effects of HMB on skeletal muscle and to examine the evidence for the
      rationale to use HMB as a nutritional supplement to exert beneficial effects on
      muscle mass and function in various conditions of health and disease. The data
      presented here indicate that the beneficial effects of HMB have been well
      characterized in strength-power and endurance exercise. HMB attenuates exercise
      induced muscle damage and enhances muscle hypertrophy and strength, aerobic
      performance, resistance to fatigue, and regenerative capacity. HMB is
      particularly effective in untrained individuals who are exposed to strenuous
      exercise and in trained individuals who are exposed to periods of high physical
      stress. The low effectiveness of HMB in strength-trained athletes could be due to
      the suppression of the proteolysis that is induced by the adaptation to training,
      which may blunt the effects of HMB. Studies performed with older people have
      demonstrated that HMB can attenuate the development of sarcopenia in elderly
      subjects and that the optimal effects of HMB on muscle growth and strength occur
      when it is combined with exercise. Studies performed under in vitro conditions
      and in various animal models suggest that HMB may be effective in treatment of
      muscle wasting in various forms of cachexia. However, there are few clinical
      reports of the effects of HMB on muscle wasting in cachexia; in addition, most of
      these studies evaluated the therapeutic potential of combinations of various
      agents. Therefore, it has not been possible to determine whether HMB was
      effective or if there was a synergistic effect. Although most of the endogenous
      HMB is produced in the liver, there are no reports regarding the levels and the
      effects of HMB supplementation in subjects with liver disease. Several studies
      have suggested that anabolic effects of HMB supplementation on skeletal muscle do
      not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may
      be applied to enhance increases in the mass and strength of skeletal muscles in
      subjects who exercise and in the elderly and (ii) studies examining the effects
      of HMB administered alone are needed to obtain conclusions regarding the specific
      effectiveness in attenuating muscle wasting in various muscle-wasting disorders.

PMID- 28493409
TI  - Unruptured sinus of Valsalva aneurysm mimicking as right atrial tumor.
AB  - Sinus of Valsalva aneurysm is a rare congenital cardiac abnormality and is
      usually diagnosed when it ruptures. An asymptomatic 55-year-old male of
      unruptured sinus of Valsalva aneurysm of noncoronary cusp was on medical follow
      up. At 2-year follow-up, there was thrombus formation in the aneurysm, mimicking
      right atrium tumor on 2D transthoracic echocardiography. Cardiac computed
      tomography showed filling defect in the aneurysm suggestive of thrombus.
      Considering the high risk of systemic emboli surgery was performed, and aneurysm
      was repaired with Dacron patch.

PMID- 28493410
TI  - Expression and prognostic significance of programmed death protein 1 and
      programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes
      of death worldwide. In this study, we assessed the correlation between
      clinicopathologic factors with programmed cell death protein 1 (PD-1) and
      programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated
      molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic
      significance of these proteins in a subgroup of patients. We retrospectively
      evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray
      samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant
      related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001
      and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically
      related to high PD-1 expression. High PD-L1 expression was demonstrated as an
      independent poor prognostic factor for disease-free survival in addition to
      previous known factors, size >5 cm and serum albumin <=3.5 g/dL in high CD8+ TILs
      group. We have demonstrated that the combined high expression of PD-L1 and CD8+
      TIL is an important prognostic factor related to the immune checkpoint pathway in
      HCC and furthermore, there is a possibility that it could be used as a predictor
      of therapeutic response. Also, this result would be helpful in evaluating the
      applicable group of PD-1/PD-L1 blocking agent for HCC patients.

PMID- 28493411
TI  - Insulinaemia and insulin resistance in Caucasian general paediatric population
      aged 2 to 10 years: Associated risk factors.
AB  - BACKGROUND: The aim of this study is to determine values of insulinaemia,
      homeostasis model assessment (HOMA) index and quantitative insulin sensitivity
      check index (QUICKI) among a population of prepubertal Caucasian children, to
      analyse factors associated with insulin resistance (IR), and to study its
      association with cardiovascular risk factors. MATERIALS AND METHODS: Population
      based study conducted on a randomly selected sample of prepubescent Caucasian
      subjects aged 2.00 to 9.99 years old. Anthropometric measurements, blood
      pressure, and fasting blood samples were obtained, including fasting glucose,
      triglycerides, High Density Lipoprotein (HDL)-cholesterol, and insulin. In
      addition, QUICKI and HOMA indices were calculated. Generalised additive models
      for location, scale and shape (GAMLSS) was used to calculate centiles curves and
      multivariate logistic regression analysis to assess factors associated with IR.
      RESULTS: A total of 654 subjects were included. Mean values obtained for
      insulinaemia, HOMA index, and QUICKI were 3.74 MUIU/mL, 0.73, and 0.44,
      respectively, in the overall population and 3.32 MUIU/mL, 0.64 and 0.46,
      respectively, in normal weight subjects. The main factor associated with IR was
      abdominal obesity (odds ratio [OR] 3.38 [95% CI 1.44-7.94] in the subgroup aged
      2.00-5.99 years and OR 9.14 [3.42-24.41] for those aged 6.00-9.99 years). An
      increased risk of hyperglycaemia (P = 0.043), hypertriglyceridaemia (P < .001),
      and HDL < p10 (P = 0.021) was described among children aged 2.00 to 5.99 years
      with IR, and among those aged 6.00 to 9.99 years, IR was associated with an
      increased risk of hypertriglyceridaemia (P < .001). CONCLUSION: Abdominal obesity
      was the main factor associated with IR. Metabolic changes associated with IR seem
      to be present from early stages of life, which highlights the importance of the
      prevention, early diagnosis and treatment of obesity.

PMID- 28493413
TI  - Examining the emerging entrepreneurial mindset in adolescence: A study in
      Nigeria.
AB  - This study investigated the relationship of family environment, network, parental
      socio-economic status, self-efficacy and proactive personality on entrepreneurial
      intention of secondary school adolescents and the mediating role of self
      efficacy. The participants were 250 secondary school SS2 adolescents randomly
      selected from six secondary schools in Ibadan Metropolis, Ibadan, Oyo State,
      Nigeria. Structural Equation Modelling was used to analyse the data obtained from
      the participants. The results showed that all the contextual and individual
      factors had significant relationship with entrepreneurial intention and self
      efficacy partially mediated the relationship. It was suggested that counselling
      psychologists should consider the contextual and individual variables while
      assisting students in building their entrepreneurial intention.

PMID- 28493412
TI  - Reassessment of alkaline phosphatase as serum tumor marker with high specificity
      in osteosarcoma.
AB  - The goal of this study was to reassess serum alkaline phosphatase (ALP) as tumor
      marker in osteosarcoma. We retrospectively examined serum ALP levels at
      diagnosis, every therapeutic step (neoadjuvant chemotherapy, surgery, and
      adjuvant chemotherapy), metastasis, and follow-up and analyzed the role of ALP as
      tumor marker in 210 osteosarcomas. The diagnostic performances of ALP were
      validated with pathology-proven 899 other primary bone lesions. Elevated ALP at
      diagnosis was associated with inferior overall survival (OS) (Log Rank P < 0.001)
      and disease-free survival (Log Rank P = 0.005) and independently significant for
      OS in multivariate analysis (hazard ratio [HR]=2.12, P = 0.032). During therapy,
      the ALP level significantly changed according to therapeutic steps (P < 0.001 for
      patients >=15 years old, P < 0.001 for patients <15 years old) and survival (P =
      0.015 for >=15 years, P = 0.002 for <15 years), and the response of ALP to
      therapy and survival were associated (P = 0.042 for >=15 years, P = 0.036 for <15
      years). Initial ALP level was linearly correlated with tumor burden (total tumor
      volume; P = 0.016 for >=15 years, bone tumor volume; P = 0.012 for >=15 years).
      The sensitivity and specificity of ALP on diagnosis were 53.2% (95% Confidence
      Interval [CI]: 0.475-0.586) and 90.1% (95% CI: 0.888-0.913). The sensitivity of
      ALP on metastasis was 53.2% (95% CI: 0.431-0.624), and the specificity was 78.2%
      (95% CI: 0.720-0.839) at15 months postoperative and 90.0% (95% CI: 0.824-0.952)
      at 3 years postoperative. Serum ALP was found to be a valuable tumor marker with
      high specificity in osteosarcoma.

PMID- 28493414
TI  - Investigating niche partitioning of ectomycorrhizal fungi in specialized rooting
      zones of the monodominant leguminous tree Dicymbe corymbosa.
AB  - Temperate ectomycorrhizal (ECM) fungi show segregation whereby some species
      dominate in organic layers and others favor mineral soils. Weak layering in
      tropical soils is hypothesized to decrease niche space and therefore reduce the
      diversity of ectomycorrhizal fungi. The Neotropical ECM tree Dicymbe corymbosa
      forms monodominant stands and has a distinct physiognomy with vertical crown
      development, adventitious roots and massive root mounds, leading to multi-stemmed
      trees with spatially segregated rooting environments: aerial litter caches,
      aerial decayed wood, organic root mounds and mineral soil. We hypothesized that
      these microhabitats host distinct fungal assemblages and therefore promote
      diversity. To test our hypothesis, we sampled D. corymbosa ectomycorrhizal root
      tips from the four microhabitats and analyzed community composition based on
      pyrosequencing of fungal internal transcribed spacer (ITS) barcode markers.
      Several dominant fungi were ubiquitous but analyses nonetheless suggested that
      communities in mineral soil samples were statistically distinct from communities
      in organic microhabitats. These data indicate that distinctive rooting zones of
      D. corymbosa contribute to spatial segregation of the fungal community and likely
      enhance fungal diversity.

PMID- 28493416
TI  - Parathyroidectomy for the treatment of hyperparathyroidism: Thirty-day morbidity
      and mortality.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate morbidity and mortality rates for patients with
      different levels of hyperparathyroidism (HPT) undergoing parathyroidectomy (PTX),
      specifically comparing primary hyperparathyroidism to secondary and tertiary
      hyperparathyroidism. Assess predictive factors of increased morbidity and
      mortality. STUDY DESIGN: Retrospective national database review. METHODS:
      Patients undergoing PTX, defined by Current Procedural Terminology codes 60500,
      60502, 60505, for the treatment of HPT, were identified in the American College
      of Surgeons National Surgical Quality Improvement Program database between 2006
      and 2014. Incidence of morbidity and mortality was calculated for primary,
      secondary, and tertiary HPT. A t test, analysis of variance, and chi2 analyses
      were used to assess preoperative characteristics among the three groups. RESULTS:
      A total of 21,267 patients were included in the analysis. There was an overall
      7.2% morbidity and mortality rate, including 45 (0.21%) deaths, a 1.8%
      readmission rate, and a 1.9% reoperation rate, but morbidity and mortality rates
      were widely divergent when comparing primary to secondary and tertiary HPT. PTX
      resulted in a 4.9% morbidity and mortality rate for primary HPT (n = 14,500),
      26.8% morbidity and mortality rate for secondary HPT (n = 1661), and 21.8%
      morbidity and mortality rate for tertiary HPT (n = 588). The primary reason for
      readmission was hypocalcemia (18.3%). Hematoma (7.2%) and postoperative
      hemorrhage (3.3%) were the two most common causes of reoperation. Elevated
      preoperative serum creatinine, alkaline phosphatase, and hypertension resulted in
      a higher rate of complications after PTX (P < .0001). CONCLUSIONS: Although
      surgery for primary HPT is an extremely common and safe procedure with minimal
      morbidity and mortality rates, PTX for secondary and tertiary HPT has
      significantly higher rates of morbidity and mortality, requiring special
      attention in the postoperative period. Predictive factors of poor outcomes
      include hypertension, elevated creatinine, and elevated alkaline phosphatase.
      LEVEL OF EVIDENCE: 4. Laryngoscope, 128:528-533, 2018.

PMID- 28493417
TI  - Retroesophageal course of left brachiocephalic vein: The garland vein.

PMID- 28493420
TI  - Comment on: "Comprehensive first-line magnetic resonance imaging in hypertension:
      experience from a single-center tertiary referral clinic".

PMID- 28493418
TI  - Muscle mass and association to quality of life in non-small cell lung cancer
      patients.
AB  - BACKGROUND: Cancer wasting is characterized by muscle loss and may contribute to
      fatigue and poor quality of life (QoL). Our aim was to investigate associations
      between skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) and
      selected QoL outcomes in advanced non-small cell lung cancer (NSCLC) at
      diagnosis. METHODS: Baseline data from patients with stage IIIB/IV NSCLC and
      performance status 0-2 enrolled in three randomized trials of first-line
      chemotherapy (n = 1305) were analysed. Associations between SMI (cm2 /m2 ) and
      SMD (Hounsfield units) based on computed tomography-images at the third lumbar
      level and self-reported physical function (PF), role function (RF), global QoL,
      fatigue, and dyspnoea were investigated by linear regression using flexible non
      linear modelling. RESULTS: Complete data were available for 734 patients, mean
      age 65 years. Mean SMI was 47.7 cm2 /m2 in men (n = 420) and 39.6 cm2 /m2 in
      women (n = 314). Low SMI values were non-linearly associated with low PF and RF
      (men P = 0.016/0.020, women P = 0.004/0.012) and with low global QoL (P = 0.001)
      in men. Low SMI was significantly associated with high fatigue (P = 0.002) and
      more pain (P = 0.015), in both genders, but not with dyspnoea. All regression
      analyses showed poorer physical outcomes below an SMI breakpoint of about 42-45
      cm2 /m2 for men and 37-40 cm2 /m2 for women. In both genders, poor PF and more
      dyspnoea were significantly associated with low SMD. CONCLUSIONS: Low muscle mass
      in NSCLC negatively affects the patients' PF, RF, and global QoL, possibly more
      so in men than in women. However, muscle mass must be below a threshold value
      before this effect can be detected.

PMID- 28493419
TI  - Support for alcohol policies from drinkers in the City of Tshwane, South Africa:
      Data from the International Alcohol Control study.
AB  - INTRODUCTION AND AIMS: South Africa is considering a range of alcohol policy
      reforms. This study aims to determine the magnitude of public support for 13
      alcohol policies in the Tshwane Metropolitan Municipality and whether this varies
      by demographic factors and heavy drinking status. DESIGN AND METHODS: Data are
      from the South African arm of the International Alcohol Control study, a
      household survey of adult drinkers using a multistage stratified cluster random
      sampling design. The sample included 1920 drinkers aged 18-65 years (62% men),
      with complete drinking data for 16 drinking locations on 955 persons (510 heavy
      and 445 not heavy drinkers). RESULTS: Over half (53%) of the sample were found to
      be heavy drinkers. Support varied by alcohol policy, ranging from 31% to 77%,
      with support above 50% for 11 of the 13 policies. Policy support was higher for
      policies increasing the purchase age to 21 years (77%), addressing drink driving
      (58-76%) and restricting physical availability (60-66%). There was slightly less
      support for policies restricting alcohol marketing (59%) or for policies
      increasing the price of alcohol (34-58%), especially if no justification was
      given or the funds were not earmarked. Policy support differed by age, gender,
      heavy drinking status and income. DISCUSSION AND CONCLUSIONS: Public support from
      adult drinkers for a range of alcohol policies is extensive and, as found
      elsewhere, was strongest for raising the minimum drinking age and lowest for
      increasing prices. The support from drinkers to increasing controls on alcohol
      could be one lever to getting control measures implemented. [Parry CDH,
      Trangenstein P, Lombard C, Jernigan DH, Morojele NK. Support for alcohol policies
      from drinkers in the City of Tshwane, South Africa: Data from the International
      Alcohol Control study. Drug Alcohol Rev 2017;00:000-000].

PMID- 28493421
TI  - Quantitative proteomics in plant protease substrate identification.
AB  - Contents Summary 936 I. Introduction 936 II. The quest for plant protease
      substrates - proteomics to the rescue? 937 III. Quantitative proteome comparison
      reveals candidate substrates 938 IV. Dynamic metabolic stable isotope labeling to
      measure protein turnover in vivo 938 V. Terminomics - large-scale identification
      of protease cleavage sites 939 VI. Substrate or not substrate, that is the
      question 940 VII. Concluding remarks 941 Acknowledgements 941 References 941
      SUMMARY: Proteolysis is a central regulatory mechanism of protein homeostasis and
      protein function that affects all aspects of plant life. Higher plants encode for
      hundreds of proteases, but their physiological substrates and hence their
      molecular functions remain mostly unknown. Current quantitative mass spectrometry
      based proteomics enables unbiased large-scale interrogation of the proteome and
      its modifications. Here we provide an overview of proteomics techniques that
      allow profiling of changes in protein abundance, measurement of proteome turnover
      rates, identification of protease cleavage sites in vivo and in vitro and
      determination of protease sequence specificity. We discuss how these techniques
      can help to reveal protease substrates and determine plant protease function,
      illustrated by recent studies on selected plant proteases.

PMID- 28493423
TI  - Development and validation of a sensitive UHPLC-MS/MS method for quantitative
      analysis of farrerol in rat plasma: Application to pharmacokinetic and
      bioavailability studies.
AB  - Farrerol is a 2,3-dihydro-flavonoid isolated from rhododendron. In this study, a
      sensitive and selective ultra-high performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) method was developed for the determination of farrerol
      in rat plasma. Liquid-liquid extraction by ethyl ether was used for sample
      preparation. Chromatographic separation was achieved on an Agilent UHPLC XDB-C18
      column (2.1 * 100 mm, 1.8 MUm) with water and methanol (30:70, v/v) as the mobile
      phase. An electrospray source was applied and operated in negative ion mode;
      selection reaction monitoring was used for quantification using target fragment
      ions m/z 299 -> 179 for farrerol and m/z 267 -> 252 for internal standard.
      Calibration plots were linear in the range of 2.88-1440 ng/mL for farrerol in rat
      plasma. Intra- and inter-day precisions were <11.6%, and the accuracy ranged from
      -13.9 to 11.9%. The UHPLC-MS/MS method was successfully applied in
      pharmacokinetics and bioavailability studies of farrerol in rats.

PMID- 28493422
TI  - Differences in presentation, progression and rates of arthroplasty between hip
      and knee osteoarthritis: Observations from an osteoarthritis cohort study-a clear
      role for conservative management.
AB  - AIM: To describe the natural progression and the rates of arthroplasty of a
      cohort of hip and knee osteoarthritis (OA) patients. METHODS: An observational
      study of 247 consecutive patients who attended an OA clinic between May 2008 and
      August 2009. Follow-up survey was conducted from July 2014 to December 2014, with
      the primary end point being joint replacement surgery. RESULTS: One hundred and
      sixty-seven patients had knee OA and 80 patients had hip OA. When adjusted for
      other variables (age, gender, body mass index, Kellgren-Lawrence stage, symptom
      duration, presence of OA elsewhere and pain score), patients with hip OA
      demonstrated 86% increased hazard of surgery compared to knee OA patients (95% CI
      increase of 19% to 193%). At 6 years after initial consultation, 67% of patients
      with knee OA did not require a knee replacement surgery, while 40% (30, 51) of
      hip OA patients did not undergo surgery (95% CI: 59-74%). Overall at 6 years, 58%
      of patients (95% CI: 51-64%) did not undergo joint replacement surgery.
      CONCLUSION: Knee and hip OA patients appear to behave differently, with hip OA
      patients more likely to undergo arthroplasty. There is a significant number of
      both hip OA and knee OA patients who did not require arthroplasty at the end of 6
      years, suggesting a major role for conservative therapy.

PMID- 28493424
TI  - The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins.
AB  - Protein interactions involving intrinsically disordered proteins (IDPs) comprise
      a variety of binding modes, from the well-characterized folding upon binding to
      dynamic fuzzy complexes. To date, most studies concern the binding of an IDP to a
      structured protein, while the interaction between two IDPs is poorly understood.
      In this study, NMR, smFRET, and molecular dynamics (MD) simulation are combined
      to characterize the interaction between two IDPs, the C-terminal domain (CTD) of
      protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed
      that CTD and NuMA form a fuzzy complex with remaining structural disorder.
      Multiple binding sites on both proteins were identified by molecular dynamics and
      mutagenesis studies. This study provides an atomic scenario in which two IDPs
      bearing multiple binding sites interact with each other in dynamic equilibrium.
      The combined approach employed here could be widely applicable for investigating
      IDPs and their dynamic interactions.

PMID- 28493425
TI  - Law enforcement-derived data on gabapentin diversion and misuse, 2002-2015:
      diversion rates and qualitative research findings.
AB  - PURPOSE: Recent limited epidemiologic and case reports suggest that gabapentin is
      being misused, especially among prescription opioid misusers. However, no
      apparent studies have reported data from law enforcement on the diversion and
      misuse of gabapentin. METHODS: Case report data are drawn from a quarterly survey
      of prescription drug diversion completed by a national sample of law enforcement
      and regulatory agencies who engage in drug diversion investigations. Rates of
      gabapentin diversion per 100 000 population were calculated for each quarter from
      2002 through 2015. Qualitative data are drawn from a brief questionnaire
      completed by a subsample of survey respondents and were organized and presented
      by theme. RESULTS: In total, 407 new cases of diverted gabapentin were reported
      during the time period, with diversion rates steadily increasing from zero cases
      in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population
      in the fourth quarter of 2015. Qualitative data suggest that gabapentin is being
      misused in conjunction with prescription opioids and that gabapentin and heroin
      are being combined and consumed together. Law enforcement reporters found these
      drug use trends to be contributing to gabapentin diversion. CONCLUSIONS: The
      recent increase in gabapentin diversion appears to be related to the opioid
      epidemic, based on law enforcement descriptions of gabapentin being misused in
      combination with opioids. Yet epidemiological data related to this finding is
      limited and research conducted among gabapentin misusers is needed to understand
      this problem in more depth. Greater monitoring of gabapentin abuse and diversion
      appear warranted.

PMID- 28493426
TI  - Optical coherence elastography for strain dynamics measurements in laser
      correction of cornea shape.
AB  - We describe the use of elastographic processing in phase-sensitive optical
      coherence tomography (OCT) for visualizing dynamics of strain and tissue-shape
      changes during laser-induced photothermal corneal reshaping, for applications in
      the emerging field of non-destructive and non-ablative (non-LASIK) laser vision
      correction. The proposed phase-processing approach based on fairly sparse data
      acquisition enabled rapid data processing and near-real-time visualization of
      dynamic strains. The approach avoids conventional phase unwrapping, yet allows
      for mapping strains even for significantly supra-wavelength inter-frame
      displacements of scatterers accompanied by multiple phase-wrapping. These
      developments bode well for real-time feedback systems for controlling the
      dynamics of corneal deformation with 10-100 ms temporal resolution, and for
      suitably long-term monitoring of resultant reshaping of the cornea. In ex-vivo
      experiments with excised rabbit eyes, we demonstrate temporal plastification of
      cornea that allows shape changes relevant for vision-correction applications
      without affecting its transparency. We demonstrate OCT's ability to detect
      achieving of threshold temperatures required for tissue plastification and
      simultaneously characterize transient and cumulative strain distributions,
      surface displacements, and scattering tissue properties. Comparison with
      previously used methods for studying laser-induced reshaping of cartilaginous
      tissues and numerical simulations is performed.

PMID- 28493427
TI  - DNA Identification of Commingled Human Remains from the Cemetery Relocated by
      Flooding in Central Bosnia and Herzegovina.
AB  - The floods in Bosnia and Herzegovina in May 2014 caused landslides all over the
      country. In the small village of Serici, near the town of Zenica, a landslide
      destroyed the local cemetery, relocated graves, and commingled skeletal remains.
      As the use of other physical methods of identification (facial recognition,
      fingerprint analysis, dental analysis, etc.) was not possible, DNA analysis was
      applied. DNA was isolated from 20 skeletal remains (bone and tooth samples) and
      six reference samples (blood from living relatives) and amplified using
      PowerPlex(r) Fusion and PowerPlex(r) Y23 kits. DNA profiles were generated for
      all reference samples and 17 skeletal remains. A statistical analysis
      (calculation of paternity, maternity, and sibling indexes and matching
      probabilities) resulted in 10 positive identifications. In this study, 5
      individuals were identified based on one reference sample. This has once again
      demonstrated the significance of DNA analysis in resolving the most complicated
      cases, such as the identification of commingled human skeletal remains.

PMID- 28493428
TI  - Optical, Thermal, and Mechanical Characterization of Ga2 Se3 -Added GLS Glass.
AB  - Gallium lanthanum sulfide glass (GLS) has been widely studied in the last 40
      years for middle-infrared applications. In this work, the results of the
      substitution of selenium for sulphur in GLS glass are described. The samples are
      prepared via melt-quench method in an argon-purged atmosphere. A wide range of
      compositional substitutions are studied to define the glass-forming region of the
      modified material. The complete substitution of Ga2 S3 by Ga2 Se3 is achieved by
      involving new higher quenching rate techniques compared to those containing only
      sulfides. The samples exhibiting glassy characteristics are further
      characterized. In particular, the optical and thermal properties of the sample
      are investigated in order to understand the role of selenium in the formation of
      the glass. The addition of selenium to GLS glass generally results in a lower
      glass transition temperature and an extended transmission window. Particularly,
      the IR edge is found to be extended from about 9 um for GLS glass to about 15 um
      for Se-added GLS glass defined by the 50% transmission point. Furthermore, the
      addition of selenium does not affect the UV edge dramatically. The role of
      selenium is hypothesized in the glass formation to explain these changes.

PMID- 28493429
TI  - Trust and risk: a model for medical education.
AB  - CONTEXT: Health care delivery, and therefore medical education, is an inherently
      risky business. Although control mechanisms, such as external audit and
      accreditation, are designed to manage risk in clinical settings, another approach
      is 'trust'. The use of entrustable professional activities (EPAs) represents a
      deliberate way in which this is operationalised as a workplace-based assessment.
      Once engaged with the concept, clinical teachers and medical educators may have
      further questions about trust. OBJECTIVES: This narrative overview of the trust
      literature explores how risk, trust and control intersect with current thinking
      in medical education, and makes suggestions for potential directions of enquiry.
      METHODS: Beyond EPAs, the importance of trust in health care and medical
      education is reviewed, followed by a brief history of trust research in the wider
      literature. Interpersonal and organisational levels of trust and a model of trust
      from the management literature are used to provide the framework with which to
      decipher trust decisions in health care and medical education, in which risk and
      vulnerability are inherent. CONCLUSIONS: In workplace learning and assessment,
      the language of 'trust' may offer a more authentic and practical vocabulary than
      that of 'competency' because clinical and professional risks are explicitly
      considered. There are many other trust relationships in health care and medical
      education. At the most basic level, it is helpful to clearly delineate who is the
      trustor, the trustee, and for what task. Each relationship has interpersonal and
      organisational elements. Understanding and considered utilisation of trust and
      control mechanisms in health care and medical education may lead to systems that
      maturely manage risk while actively encouraging trust and empowerment.

PMID- 28493431
TI  - Breaking the real language barrier in care for older people.

PMID- 28493430
TI  - First case of bacteremia caused by Janibacter hoylei.
AB  - Janibacter hoylei has previously been isolated only from an air sample in the
      upper atmosphere and clinical significance of J. hoylei was not yet established.
      Herein, we report a case of bacteremia caused by J. hoylei. An 8-week-old
      previously healthy male infant presented to the emergency room with fever. Blood
      culture yielded growth of Gram-positive bacilli and this microorganism could not
      be identified with conventional phenotypic methods. The isolate was identified by
      16S rRNA gene sequencing, and the patient was successfully treated with
      vancomycin. To our knowledge, this is the first report of the recovery of J.
      hoylei in humans. This case shows that J. hoylei can be a potential pathogen in
      young children.

PMID- 28493432
TI  - Phenol metabolism and preservation of fresh in-hull walnut stored in modified
      atmosphere packaging.
AB  - BACKGROUND: The effects of modified atmosphere packaging (MAP) on phenol
      metabolism and preservation of fresh in-hull walnuts have been investigated.
      Fruit was packaged under MAP1 (film thickness, 30 MUm), MAP2 (45 MUm) and MAP3
      (50 MUm) and stored at -0.5 to 1.0  degrees C for up to 60 days. RESULTS:
      Firmness, soluble solid concentration, total phenols, total flavonoids and total
      antioxidant activity of the green hull were maintained at higher levels under the
      MAP conditions, whereas decay incidence was lower compared to the control during
      storage. Green hull of fruit under MAP conditions contained lower polyphenol
      oxidase activity than the control and the peroxidase activity was at a similar
      level to the control after 18 days. Phenylalanine ammonialyase activity was
      enhanced by MAP conditions, with two peaks on days 18 and 36. Until day 60, the
      peroxide value and acid value of kernel oils under MAP conditions were lower than
      that of the control. CONCLUSION: The MAP3 treatment was most effective for
      maintaining kernel quality. The protective role of MAP conditions on phenolic
      contents in green hull may contribute to the mitigation of decay and the
      maintenance of kernel quality. (c) 2017 Society of Chemical Industry.

PMID- 28493433
TI  - Highly Active and Iso-Selective Catalysts for the Ring-Opening Polymerization of
      Cyclic Esters using Group 2 Metal Initiators.
AB  - A series of alkali and alkaline earth (Ae) metal complexes bearing 1,2
      phenylene(bis-diphenylphosphinothioic/selenoic amine) [{Ph2 P(E)NH}2 C6 H4 ] (E=S
      (1-H2); Se (2-H2) ligands are reported. Alkali metal complexes [{Ph2 P(S)N}2 C6
      H4 ]Na(THF)4 (3 a) [{Ph2 P(Se)N}2 C6 H4 ]Na(THF)4 (3 b), and [{Ph2 P(Se)N}2 C6 H4
      ]K(THF)5 (4 b) were obtained in good yield by treating protic ligands 1-H2 or 2
      H2 with metal hexamethyldisilazides [MN(SiMe3 )2 ] (M=Na or K) at ambient
      temperature. The Ae metal complexes formulated as [{Ph2 P(E)N}2 C6 H4 ]M(THF)3
      [E=S, M=Ca (5 a), Sr (6 a), Ba (7 a); E=Se, M=Ca (5 b), Sr (6 b), Ba (7 b)] can
      be synthesized by using two routes. The molecular structures of the free ligand 1
      H2 and metal complexes 5 a,b-7 a,b in their solid states were established.
      Complexes 3 a and 3 b are isostructural; however, in complex 4 b, an attachment
      different from ligand 2 was observed. The complexes 5 a,b-7 a,b are isostructural
      and each metal ion exhibits a distorted pentagonal bipyramidal geometry around
      it. All Ae metal complexes 5 a,b-7 a,b were tested for the ring-opening
      polymerization (ROP) of racemic lactide (rac-LA) and epsilon-caprolactone
      (epsilon-CL) at room temperature. Calcium complexes 5 a and 5 b show excellent
      iso-selectivity, with Pi values of 0.78-0.87 at 298 K and with a high degree of
      polymerization control, whereas the corresponding strontium complexes 6 a and 6 b
      exhibit moderate iso-selectivity, and barium complexes 7 a and 7 b yield only
      atactic polylactides (PLAs). In all cases, the catalyst initiates the ROP
      catalytic cycle in the absence of any external initiator. Kinetic studies of the
      polymerization reactions indicate the relative order of polymerization rate
      increases with increase in the size of the metal ion: Ba>Sr>Ca.

PMID- 28493434
TI  - Carbon Thin Film Wrapped around a Three-Dimensional Nitrogen-Doped Carbon
      Scaffold for Superior-Performance Supercapacitors.
AB  - A carbon thin film/carbon foam core/sheath structure was synthesized by chemical
      vapor deposition (CVD) on carbonized melamine foam. It has a specific capacitance
      of 310 F g-1 at a current density of 1 A g-1 and shows outstanding
      electrochemical performance in both aqueous and water-in-salt electrolytes.
      Electrochemical analysis by cyclic voltammetry and galvanostatic charge/discharge
      testing revealed a large capacitive contribution up to more than 90 % of its
      total capacitance. The core/sheath structure has advantages in ion transport and
      a high degree of utilization of the electrode surface, and the synthetic process
      provides a way to coat carbon thin film on any substrate by nickel-catalyzed CVD.

PMID- 28493435
TI  - A Fast Peak-Searching Algorithm for Ultrasonic Elastography.
AB  - Tissue axial strain estimation with ultrasound elastography has become a hot
      field in recent years. However, for keypoints tracking-based elastography
      algorithms, locating extrema in multimodal ultrasonic radiofrequency signals is
      still a challenging problem. In this paper, a new method is proposed to locate
      the local maxima and minima of the RF signals directly without derivation
      operation. This algorithm can accurately locate extrema even if disturbed peaks
      resulting from different noise exist. Furthermore, the new algorithm can speed up
      approximately 79% of the implementation process as compared with the standard
      cross-correlation method on the same computing platform. In addition, the
      elastographic signal-to-noise ratio and the contrast-to-noise ratio are also
      significantly improved with this new method.

PMID- 28493436
TI  - Enantioselective analysis of bambuterol in human plasma using microwave-assisted
      chiral derivatization coupled with ultra high performance liquid chromatography
      and tandem mass spectrometry.
AB  - In this study, an enantioselective analytical method based on microwave-assisted
      chiral derivatization coupled with ultra high performance liquid chromatography
      and tandem mass spectrometry was developed for the determination of bambuterol
      enantiomers in human plasma. The chiral derivatization reaction was greatly
      accelerated by microwave irradiation. Under the optimized conditions, both the
      derivatization time and separation time on column was only 3 min, and the lower
      limit of quantification was 2.5 pg/mL. The recoveries were in the range of 90.1
      93.0% without significant matrix effect. Compared with the conventional heating
      chiral derivatization, microwave-assisted chiral derivatization obtained higher
      chiral derivatization yields with much shorter time due to the effect of
      microwave irradiation. Furthermore, the racemization during the derivatization
      reaction was systematically investigated. The results showed the concentration of
      acetic acid and the reaction time had significant effects on the racemization,
      which could be well controlled during microwave-assisted chiral derivatization
      for the short reaction time. Finally, this novel approach was demonstrated by
      determining bambuterol in human plasma of a clinical pharmacokinetic study in
      eight healthy volunteers. On the basis of the results, microwave-assisted chiral
      derivatization coupled with ultra high performance liquid chromatography and
      tandem mass spectrometry as a simple and effective enantioselective analysis
      technique for the determination of chiral drugs in complex biological samples
      showed great promise.

PMID- 28493437
TI  - Extended axial imaging range, widefield swept source optical coherence tomography
      angiography.
AB  - We developed a high-speed, swept source OCT system for widefield OCT angiography
      (OCTA) imaging. The system has an extended axial imaging range of 6.6 mm. An
      electrical lens is used for fast, automatic focusing. The recently developed
      split-spectrum amplitude and phase-gradient angiography allow high-resolution
      OCTA imaging with only two B-scan repetitions. An improved post-processing
      algorithm effectively removed trigger jitter artifacts and reduced noise in the
      flow signal. We demonstrated high contrast 3 mm*3 mm OCTA image with 400*400
      pixels acquired in 3 seconds and high-definition 8 mm*6 mm and 12 mm*6 mm OCTA
      images with 850*400 pixels obtained in 4 seconds. A widefield 8 mm*11 mm OCTA
      image is produced by montaging two 8 mm*6 mm scans. An ultra-widefield (with a
      maximum of 22 mm along both vertical and horizontal directions) capillary
      resolution OCTA image is obtained by montaging six 12 mm*6 mm scans.

PMID- 28493439
TI  - Very late presentation of a disorder of sex development.
AB  - Disorders of sex development generally present in the neonatal period with
      ambiguity of external genitalia. We report a very old male patient presenting at
      75 years because of panhypopituitarism and a large nonsecreting pituitary
      macroadenoma secondary to long-standing primary hypogonadism due to 46,XX sex
      reversal disorder now first diagnosed. Sex development disorders may go
      unrecognised for the entire life span, despite infertility and long-standing
      primary gonadic failure may lead to uncommon complications.

PMID- 28493438
TI  - Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive
      syndrome of progressive microcephaly, hypomyelination, and epileptic
      encephalopathy.
AB  - Aminoacyl-transfer RNA (tRNA) synthetases ligate amino acids to specific tRNAs
      and are essential for protein synthesis. Although alanyl-tRNA synthetase (AARS)
      is a synthetase implicated in a wide range of neurological disorders from Charcot
      Marie-Tooth disease to infantile epileptic encephalopathy, there have been
      limited data on their pathogenesis. Here, we report loss-of-function mutations in
      AARS in two siblings with progressive microcephaly with hypomyelination,
      intractable epilepsy, and spasticity. Whole-exome sequencing identified that the
      affected individuals were compound heterozygous for mutations in AARS gene,
      c.2067dupC (p.Tyr690Leufs*3) and c.2738G>A (p.Gly913Asp). A lymphoblastoid cell
      line developed from one of the affected individuals showed a strong reduction in
      AARS abundance. The mutations decrease aminoacylation efficiency by 70%-90%. The
      p.Tyr690Leufs*3 mutation also abolished editing activity required for hydrolyzing
      misacylated tRNAs, thereby increasing errors during aminoacylation. Our study has
      extended potential mechanisms underlying AARS-related disorders to include
      destabilization of the protein, aminoacylation dysfunction, and defective editing
      activity.

PMID- 28493440
TI  - Tear production, intraocular pressure and conjunctival bacterial flora in
      selected captive wild ruminants.
AB  - OBJECTIVE: Evaluation of tear production (Schirmer's tear test, STT) and
      measurement of intraocular pressure (IOP) were performed in a population of
      captive wild ungulates in a Slovenian ZOO during routine annual health check.
      ANIMALS STUDIED: In total, 10 fallow deer (Dama dama), 25 mouflons (Ovis aries
      musimon), 20 alpine ibexes (Capra ibex), and three alpine chamois (Rupicapra
      rupicapra) were included in the study. METHODS: Tear production was performed by
      Schirmer's tear test, IOP was measured with an applanation tonometer, and
      ophthalmological examination was conducted with slit-lamp biomicroscopy and
      indirect ophthalmoscopy. Conjunctival swabs were taken and submitted for aerobic
      bacteriology and for detection of Chlamydia spp. and Mycoplasma spp. tested by
      PCR. RESULTS: Average tear production (in mm/min) was 17.8 +/- 3.16 for fallow
      deer, 17.9 +/- 3.87 for mouflons, and 11.7 +/- 3.87 for ibexes. Mean intraocular
      pressure (IOP, in mm Hg) was 14.1 +/- 2.48 for fallow deer, 14.9 +/- 2.20 for
      mouflons, and 13.1 +/- 2.43 for ibexes. For chamois, average tear production and
      IOP were 14.5 +/- 3.0 and 10.2 +/- 2.5, respectively; this is the first record of
      STT I and IOP in chamois. Bacteriological swabs were positive for bacteria in
      100% of the fallow deer, 56% of mouflons, 35% of ibexes, and 100% of chamois.
      Gram-positive bacteria were predominant. Moraxella spp., Chlamydia spp., and
      Mycoplasma spp. were not detected. CONCLUSION: The reported values were obtained
      in animals under manual restraint only to be applicative in similar conditions.

PMID- 28493441
TI  - UHPLC-ESI-MS/MS determination and pharmacokinetics of pinoresinol glucoside and
      chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides
      Oliv extract.
AB  - This study aimed to develop a specific UHPLC-ESI-MS/MS method for simultaneous
      determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid
      in rat plasma after oral administration of Eucommia ulmoides. The chromatographic
      separation was achieved on a Hypersil GOLD column with gradient elution by using
      a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile
      phase at a flow rate of 200 MUL/min. A tandem mass spectrometric detection was
      conducted using multiple-reaction monitoring via an electrospray ionization
      source in negative ionization mode. Samples were pre-treated by a single-step
      protein precipitation with acetonitrile, and bergenin was used as internal
      standard. After oral administration of 3 mL/kg E. ulmoides extract in rats, the
      maximum plasma concentrations of pinoresinol glucoside and chlorogenic acid were
      57.44 and 61.04 ng/mL, respectively. The times to reach the maximum plasma
      concentration were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic
      acid, respectively. The intra- and inter-day precision (RSD) values for the two
      analytes were <2.46 and 5.15%, respectively, and the accuracy (RE) values ranged
      from -12.76 to 0.00. This is the first study on pharmacokinetics of bioactive
      compounds in rat plasma after oral administration of E. ulmoides extract.

PMID- 28493442
TI  - uPA-derived peptide, A6 is involved in the suppression of lipopolysaccaride
      promoted inflammatory osteoclastogenesis and the resultant bone loss.
AB  - INTRODUCTION: Chronic inflammatory diseases such as rheumatoid arthritis and
      periodontitis frequently cause bone destruction. Inflammation-induced bone loss
      results from the increase of bone-resorbing osteoclasts. Recently, we
      demonstrated that urokinase type plasminogen activator (uPA) suppressed
      lipopolysaccaride (LPS)-inflammatory osteoclastogenesis through the adenosine
      monophosphate-activated protein kinase (AMPK) pathway, whereas its receptor
      (uPAR) promoted that through the Akt pathway. METHODS: We investigated the
      effects of uPA-derived peptide (A6) in the LPS-induced inflammatory
      osteoclastogenesis and bone destruction. RESULTS: We found that A6 attenuated
      inflammatory osteoclastogenesis and bone loss induced by LPS in mice. We also
      showed that A6 attenuated the LPS-promoted inflammatory osteoclastogenesis by
      inactivation of NF-kappaB in RAW264.7 mouse monocyte/macrophage lineage cells.
      Furthermore, we showed that A6 attenuated the Akt phosphorylation, and promoted
      the AMPK phosphorylation. CONCLUSION: A6 is involved in the suppression of LPS
      promoted inflammatory osteoclastgensis and bone destruction by regulating the
      AMPK and Akt pathways. These findings provide a basis for clinical strategies to
      improve the bone loss caused by inflammatory diseases.

PMID- 28493444
TI  - Impact of hyperlipidaemia on intermediary metabolism, faecal microbial
      metabolites and urinary characteristics of lipoprotein lipase deficient vs.
      normal cats.
AB  - Findings in humans and rats indicate that hyperlipidaemia may be associated with
      enhanced endogenous oxalate (Ox) synthesis, which may be relevant for calcium
      oxalate (CaOx) urolith formation. Moreover, changes in lipid metabolism are
      proposed to negatively affect gut microbiota. This study aimed to investigate
      those potential interactions in hyperlipidaemic cats. Therefore, 10 normal
      control cats and seven lipoprotein lipase (LPL)-deficient cats were fed a low-fat
      diet for seven weeks. During the last week of the study, cats were housed in
      metabolic cages to collect urine and faeces. Blood was taken on the last day of
      the study. The LPL-deficient cats had significantly higher serum triglyceride
      concentrations than normal cats, while lactate dehydrogenase (LDH) activity was
      not different. Urinary relative supersaturation with CaOx, urinary Ox, calcium,
      and citrate excretions, and urine pH did not differ between groups. Lower faecal
      acetic, propionic and total short-chain fatty acid concentrations were observed
      in the LPL-deficient cats. In conclusion, hyperlipidaemia does not appear to be a
      specific risk factor for CaOx urolith formation in cats. In contrast to results
      in rats, hyperlipidaemia was not accompanied by elevated serum LDH activity. As
      LDH can synthesise Ox from glycolate or other precursors, this might be one
      possible explanation for the similar urinary parameters in the LPL-deficient and
      normal cats. Non-diet-induced hyperlipidaemia was not associated with marked
      changes in faecal microbial metabolites, suggesting no differences in the
      composition of the intestinal microbiota.

PMID- 28493443
TI  - Natural alkaloid bouchardatine ameliorates metabolic disorders in high-fat diet
      fed mice by stimulating the sirtuin 1/liver kinase B-1/AMPK axis.
AB  - BACKGROUND AND PURPOSE: Promoting energy metabolism is known to provide
      therapeutic effects for obesity and associated metabolic disorders. The present
      study evaluated the therapeutic effects of the newly identified bouchardatine
      (Bou) on obesity-associated metabolic disorders and the molecular mechanisms of
      these effects. EXPERIMENTAL APPROACH: The molecular mode of action of Bou for its
      effects on lipid metabolism was first examined in 3T3-L1 adipocytes and HepG2
      cells. This was followed by an evaluation of its metabolic effects in mice fed a
      high-fat diet for 16 weeks with Bou being administered in the last 5 weeks.
      Further mechanistic investigations were conducted in pertinent organs of the mice
      and relevant cell models. KEY RESULTS: In 3T3-L1 adipocytes, Bou reduced lipid
      content and increased sirtuin 1 (SIRT1) activity to facilitate liver kinase B1
      (LKB1) activation of AMPK. Chronic administration of Bou (50 mg?kg-1 every other
      day) in mice significantly attenuated high-fat diet-induced increases in body
      weight gain, dyslipidaemia and fatty liver without affecting food intake and no
      adverse effects were detected. These metabolic effects were associated with
      activation of the SIRT1-LKB1-AMPK signalling pathway in adipose tissue and liver.
      Of particular note, UCP1 expression and mitochondrial biogenesis were increased
      in both white and brown adipose tissues of Bou-treated mice. Incubation with Bou
      induced similar changes in primary brown adipocytes isolated from mice.
      CONCLUSIONS AND IMPLICATIONS: Bou may have therapeutic potential for obesity
      related metabolic diseases by increasing the capacity of energy expenditure in
      adipose tissues and liver through a mechanism involving the SIRT1-LKB1-AMPK axis.

PMID- 28493445
TI  - Informed consent, community engagement, and study participation at a research
      site in Kigali, Rwanda.
AB  - People enroll in medical research for many reasons ranging from decisions
      regarding their own or family members' health situation to broader considerations
      including access to health and financial resources. In socially vulnerable
      communities the choice to participate is often based on a risk-benefit assessment
      that goes beyond the medical aspects of the research, and considers the benefits
      received. In this qualitative study, we examined the motivations of Rwandan women
      to participate in a non-commercial collaborative research study examining the
      safety, acceptability, and adherence of a contraceptive vaginal ring in Rwanda
      juxtaposed with the perceptions of the research within the community. 351 women
      attended the screening visit, four were excluded because they were not able to
      complete the assessment of understanding. The remaining participants' ages ranged
      from 17 to 38 and 80% had primary level of education or below. 120 were enrolled.
      Findings highlighted motivations for joining the study that were relayed both
      formally by the clinic (e.g. testing and treatment) and informally by the
      community including the positive aspects of the ring. There were also some
      negative rumors circulating regarding the research site, likely from excluded
      participants who faced potential stigma based on that exclusion. It was
      understood by most participants that they were enrolled in a research study and
      participants actively sought out enrollment in the research for a variety of
      reasons. The experiences demonstrate that although inequalities in access to
      health care may create conflicting situations around the study, it is possible to
      form partnerships between a research center and participants/their partners, for
      research about reproductive health.

PMID- 28493446
TI  - Family perception of unmet support needs following a diagnosis of congenital
      coronary anomaly in children: Results of a survey.
AB  - BACKGROUND: Long-term outcome data on patients with anomalous aortic origin of
      coronary arteries (AAOCA) is sparse and they are often managed in a nonuniform
      manner. There is subjective perception of anxiety and unmet needs in these
      patients and families. METHODS: An online survey of 13 questions was sent to 74
      families of patients with AAOCA between May and October 2015. Descriptive
      statistics were performed. RESULTS: A total of 31 (47%) families responded. Of
      these, 27 expressed the need to interact with other patients/families with AAOCA.
      The majority were interested in either face-to-face meetings (77%) or online
      support groups (71%). Regarding content of the meeting, 74% were interested in
      brief talks by medical personnel/families, 58% suggested informal interactions
      with families, 55% proposed a structured discussion with a moderator and 39%
      mentioned fun activities/games. Regarding participants in these meetings, 90%
      would like to include healthcare providers, 61% suggested including family
      friends, 58% wished to include psychologists and 16% mentioned including social
      workers. The families currently use various social media including Facebook
      (87%), YouTube (39%), Google+ (36%), and LinkedIn (32%). For future online
      resources, 77% of families would like a Facebook site, an informative website
      (58%), a blog (52%), or an open forum (29%). The majority of the families (77%)
      were interested in attending a dedicated AAOCA meeting. CONCLUSION: There appears
      to be an unmet need for family support in those affected by AAOCA, a substantial
      life changing diagnosis for patients and families. Further research is needed to
      assess quality of life in this population.

PMID- 28493448
TI  - Utility of an immunocytochemical assay using aqueous humor in the diagnosis of
      feline infectious peritonitis.
AB  - OBJECTIVE: In cats suffering from feline infectious peritonitis (FIP) without
      effusion, antemortem diagnosis is challenging. Uveitis is common in these cats.
      It was the aim of this study to evaluate sensitivity and specificity of an
      immunocytochemical assay (ICC) in aqueous humor of cats suspected of having FIP.
      ANIMALS STUDIED: The study included 26 cats with immunohistochemically confirmed
      FIP and 12 control cats for which FIP was suspected due to similar clinical or
      laboratory changes, but which suffered from other diseases confirmed via
      histopathology. PROCEDURES: All aqueous humor samples were collected postmortem
      by paracentesis. ICC was carried out as avidin-biotin complex method.
      Sensitivity, specificity, and the overall accuracy including 95% confidence
      intervals (95% CI) were calculated. RESULTS: Immunocytochemistry was positive in
      16 of 25 cats with FIP and 2 of 11 control cats (one cat with lymphoma, one with
      pulmonary adenocarcinoma). Aqueous humor samples of one cat with FIP and of one
      control cat were excluded from statistical analysis. Sensitivity was 64.0% (95%
      CI: 42.5-82.0); specificity 81.8% (95% CI: 48.2-97.7); and overall accuracy 69.4%
      (95% CI: 51.9-83.7). CONCLUSIONS: As false-positive results occurred and
      specificity is most important in the diagnosis of FIP, the diagnostic utility of
      ICC in aqueous humor is limited. Further studies are required to clarify the
      origin of false-positive ICC results.

PMID- 28493447
TI  - The outcomes and prognostic factors of fetal hydrothorax associated with trisomy
      21.
AB  - OBJECTIVES: To determine the characteristics, outcomes, and prognostic factors of
      fetal hydrothorax (FHT) with trisomy 21. METHODS: A nationwide survey was
      conducted on FHT fetuses with trisomy 21 delivered after 22 weeks' gestation
      between January 2007 and December 2011 at perinatal centers. RESULTS: The 91
      cases of FHT with trisomy 21 included 28 (30.8%) diagnosed in utero and 63
      (69.2%) diagnosed after birth. The natural remission rate was 6.6% (6/91).
      Thoracoamniotic shunting was performed in 14.3% (13/91) of cases. The survival
      rates of the hydropic, nonhydropic, and total cases were 47.0% (31/66), 84.0%
      (21/25), and 57.1% (52/91), respectively. The crude odds ratio for death was 8.2
      (p = 0.003) for fetuses diagnosed at 26-30 weeks of gestational age (vs >=30
      weeks), 5.9 (p = 0.003) for hydrops, 4.0 (p = 0.04) for bilateral pleural
      effusion, 0.68 (p = 0.42) for associated cardiovascular anomalies, and 2.1 (p =
      0.26) for thoracoamniotic shunting (vs no fetal therapy). CONCLUSIONS: The
      prognosis of FHT with trisomy 21 was not very poor, but it was still worse than
      that of primary FHT. Hydrops, an early gestational age at the diagnosis and
      bilateral effusion, but not associated anomalies, were risk factors for death.
      Fetal therapy showed no survival benefit for FHT with trisomy 21. (c) 2017 John
      Wiley & Sons, Ltd.

PMID- 28493449
TI  - Formation of Tough Films by Evaporation of Water from Dispersions of Elastomer
      Microspheres Crosslinked with Rotaxane Supramolecules.
AB  - Compared to rigid microspheres that consist, for example, of polystyrene or
      silica, soft and deformable elastomer microspheres can be used to generate
      colorless transparent films upon evaporating the solvent from microsphere
      containing dispersions. To obtain tough films, a post-polymerization reaction to
      crosslink the microspheres is usually necessary, which requires extra additives
      during the drying process. This restriction renders this film-formation
      technology complex and rather unsuitable for applications in which impurities are
      undesirable. In the present study, it is demonstrated that tough elastomer
      microspheres that are crosslinked with rotaxanes can form tough bulk films upon
      evaporation of water from microsphere dispersions, so that post-polymerization
      reactions are not required. The results of this study should thus lead to new
      applications including coatings for biomaterials that need complete removal of
      all impurities from the materials prior to use.

PMID- 28493450
TI  - Functionally specialised birds respond flexibly to seasonal changes in fruit
      availability.
AB  - Interactions between resource and consumer species result in complex ecological
      networks. The overall structure of these networks is often stable in space and
      time, but little is known about the temporal stability of the functional roles of
      consumer species in these networks. We used a trait-based approach to investigate
      whether consumers (frugivorous birds) show similar degrees of functional
      specialisation on resources (plants) in ecological networks across seasons. We
      additionally tested whether closely related bird species have similar degrees of
      functional specialisation and whether birds that are functionally specialised on
      specific resource types within a season are flexible in switching to other
      resource types in other seasons. We analysed four seasonal replicates of two
      species-rich plant-frugivore networks from the tropical Andes. To quantify fruit
      preferences of frugivorous birds, we projected their interactions with plants
      into a multidimensional plant trait space. To measure functional specialisation
      of birds, we calculated a species' functional niche breadth (the extent of
      seasonal plant trait space utilised by a particular bird) and functional
      originality (the extent to which a bird species' fruit preference functionally
      differs from those of other species in a seasonal network). We additionally
      calculated functional flexibility, i.e. the ability of bird species to change
      their fruit preference across seasons in response to variation in plant
      resources. Functional specialisation of bird species varied more among species
      than across seasons, and phylogenetically similar bird species showed similar
      degrees of functional niche breadth (phylogenetic signal lambda = 0.81) and
      functional originality (lambda = 0.89). Additionally, we found that birds with
      high functional flexibility across seasons had narrow functional niche breadth
      and high functional originality per season, suggesting that birds that are
      seasonally specialised on particular resources are most flexible in switching to
      other fruit resources across seasons. The high flexibility of functionally
      specialised bird species to switch seasonally to other resources challenges the
      view that consumer species rely on functionally similar resources throughout the
      year. This flexibility of consumer species may be an important, but widely
      neglected mechanism that could potentially stabilise consumer-resource networks
      in response to human disturbance and environmental change.

PMID- 28493451
TI  - The effect of an electronic health record-based tool on abnormal pediatric blood
      pressure recognition.
AB  - BACKGROUND: Recognition of high blood pressure (BP) in children is poor, partly
      due to the need to compute age-sex-height referenced percentiles. This study
      examined the change in abnormal BP recognition before versus after the
      introduction of an electronic health record (EHR) app designed to calculate BP
      percentiles with a training lecture. METHODS AND RESULTS: Clinical data were
      extracted on all ambulatory, non-urgent encounters for children 3-18 years old
      seen in primary care, endocrinology, cardiology, or nephrology clinics at an
      urban, academic hospital in the year before and the year after app introduction.
      Outpatients with at least 1 BP above the age-gender-height referenced 90th
      percentile were included. Abnormal BP recognition was defined as a BP related ICD
      9 code, referral to nephrology or cardiology, an echocardiogram or renal
      ultrasound to evaluate BP concern, or a follow-up primary care visit for BP
      monitoring. Multivariable adjusted logistic regression compared odds of
      recognition before and after app introduction. Of 78 768 clinical encounters,
      3521 had abnormal BP in the pre- and 3358 in the post-app period. App use
      occurred in 13% of elevated BP visits. Overall, abnormal BP was recognized in
      4.9% pre-app period visits and 7.1% of visits post-app (P < .0001). Recognition
      was significantly higher when the app was actually used (adjusted OR 3.17 95% CI
      2.29-4.41, P < .001). Without app use recognition was not different. CONCLUSIONS:
      BP app advent modestly increased abnormal BP recognition in the entire cohort,
      but actual app use was associated with significantly higher recognition.
      Predictors of abnormal BP recognition deserve further scrutiny.

PMID- 28493452
TI  - Suitability of selected chromatographic columns for analysis of fatty acids in
      dialyzed patients.
AB  - Gas chromatography-mass spectrometry is a preferred method for fatty acid (FA)
      analysis in biofluids from patients with metabolic diseases. Complex
      characteristics of FAs make their analysis particularly challenging. Selection of
      an appropriate chromatographic column is particularly important component of the
      process as it provides optimal separation and detection of possibly all FAs
      present in the sample. However, no accurate protocol for comparative evaluation
      of capillary columns for the analysis of whole serum FA profile in patients with
      chronic kidney disease (CKD) has been developed thus far. Therefore, in the
      present study four columns were examined to select the one providing optimal
      separation and determination of FA profiles in this group of patients. Moreover,
      serum FA profiles obtained with the selected column in CKD patients subjected to
      peritoneal dialysis and healthy controls were compared. Thirty-seven component
      FAME Mix and sera from CKD patients were used to optimize chromatographic
      conditions and to select the most appropriate column. The ZB-5 column turned out
      to be the most appropriate for the analysis of whole FA profile in CKD patients'
      sera. Then, this column was used to compare FA profiles in patients subjected to
      peritoneal dialysis and in healthy controls. The analysis demonstrated many
      abnormalities in the FA profile of CKD patients. Further studies involving larger
      groups of patients presenting with other stages of CKD are required to explain
      the impact of the disease progression on composition of serum FAs.

PMID- 28493453
TI  - A survey to establish current practice in addressing work participation with
      inflammatory arthritis in the Irish clinical setting.

PMID- 28493454
TI  - Cryo scanning electron microscopy of Plasmodium falciparum-infected erythrocytes.
AB  - Plasmodium falciparum invades erythrocytes as an essential part of their life
      cycle. While living inside erythrocytes, the parasite remodels the cell's
      intracellular organization as well as its outer surface. Late trophozoite-stage
      parasites and schizonts introduce numerous small protrusions on the erythrocyte
      surface, called knobs. Current methods for studying these knobs include atomic
      force microscopy and electron microscopy. Standard electron microscopy methods
      rely on chemical fixation and dehydration modifying cell size. Here, a novel
      method is presented using rapid freezing and scanning electron microscopy under
      cryogenic conditions allowing for high resolution and magnification of
      erythrocytes. This novel technique can be used for precise estimates of knob
      density and for studies on cytoadhesion.

PMID- 28493460
TI  - Single-cell genomics reveals pyrrolysine-encoding potential in members of
      uncultivated archaeal candidate division MSBL1.
AB  - Pyrrolysine (Pyl), the 22nd canonical amino acid, is only decoded and synthesized
      by a limited number of organisms in the domains Archaea and Bacteria. Pyl is
      encoded by the amber codon UAG, typically a stop codon. To date, all known Pyl
      decoding archaea are able to carry out methylotrophic methanogenesis. The
      functionality of methylamine methyltransferases, an important component of
      corrinoid-dependent methyltransfer reactions, depends on the presence of Pyl.
      Here, we present a putative pyl gene cluster obtained from single-cell genomes of
      the archaeal Mediterranean Sea Brine Lakes group 1 (MSBL1) from the Red Sea.
      Functional annotation of the MSBL1 single cell amplified genomes (SAGs) also
      revealed a complete corrinoid-dependent methyl-transfer pathway suggesting that
      members of MSBL1 may possibly be capable of synthesizing Pyl and metabolizing
      methylated amines.

PMID- 28493459
TI  - Enhanced NOLC1 promotes cell senescence and represses hepatocellular carcinoma
      cell proliferation by disturbing the organization of nucleolus.
AB  - The nucleolus is a key organelle that is responsible for the synthesis of rRNA
      and assembly of ribosomal subunits, which is also the center of metabolic control
      because of the critical role of ribosomes in protein synthesis. Perturbations of
      rRNA biogenesis are closely related to cell senescence and tumor progression;
      however, the underlying molecular mechanisms are not well understood. Here, we
      report that cellular senescence-inhibited gene (CSIG) knockdown up-regulated
      NOLC1 by stabilizing the 5'UTR of NOLC1 mRNA, and elevated NOLC1 induced the
      retention of NOG1 in the nucleolus, which is responsible for rRNA processing.
      Besides, the expression of NOLC1 was negatively correlated with CSIG in the aged
      mouse tissue and replicative senescent 2BS cells, and the down-regulation of
      NOLC1 could rescue CSIG knockdown-induced 2BS senescence. Additionally, NOLC1
      expression was decreased in human hepatocellular carcinoma (HCC) tissue, and the
      ectopic expression of NOLC1 repressed the proliferation of HCC cells and tumor
      growth in a HCC xenograft model.

PMID- 28493461
TI  - Ophthalmic nepafenac use in the Netherlands and Denmark.
AB  - PURPOSE: To describe nepafenac use in the Netherlands and Denmark with reference
      to its approved indications. For context, we also describe the use of ketorolac
      and diclofenac. METHODS: We identified users in the PHARMO Database Network (the
      Netherlands, 2008-2013) and the Danish national health registers (Denmark, 1994
      2014). We described prevalence of cataract surgery and duration of use in
      patients with cataract surgery with and without diabetes. RESULTS: In the
      Netherlands, 9530 nepafenac users (mean age, 71 years; 60% women) contributed 12
      691 therapy episodes, of which 21% had a recently recorded cataract surgery. Of
      2266 episodes in adult non-diabetic patients with cataract surgery, 60% had one
      bottle dispensed (treatment duration <=21 days). Of 441 episodes in adult
      diabetic patients with cataract surgery, 90% had up to two bottles dispensed
      (<=60 days). Denmark had 60 403 nepafenac users (mean age, 72 years; 58% women)
      and 73 648 episodes (41% had recorded cataract surgery). Of 26 649 nepafenac
      episodes in adult non-diabetic patients with cataract surgery, 92% had one bottle
      dispensed. Of 3801 episodes in adult diabetic patients with cataract surgery,
      99.8% had up to two bottles dispensed. Use patterns of nepafenac, ketorolac and
      diclofenac were roughly similar in the Netherlands, but not in Denmark.
      CONCLUSION: Less than half of therapy episodes were related to cataract surgery;
      around 90% of episodes with surgery were within the approved duration.
      Underrecording of ophthalmic conditions and procedures was a challenge in this
      study.

PMID- 28493462
TI  - Strong Short-Range Cooperativity in Hydrogen-Bond Chains.
AB  - Chains of hydrogen bonds such as those found in water and proteins are often
      presumed to be more stable than the sum of the individual H bonds. However, the
      energetics of cooperativity are complicated by solvent effects and the dynamics
      of intermolecular interactions, meaning that information on cooperativity
      typically is derived from theory or indirect structural data. Herein, we present
      direct measurements of energetic cooperativity in an experimental system in which
      the geometry and the number of H bonds in a chain were systematically controlled.
      Strikingly, we found that adding a second H-bond donor to form a chain can almost
      double the strength of the terminal H bond, while further extensions have little
      effect. The experimental observations add weight to computations which have
      suggested that strong, but short-range cooperative effects may occur in H-bond
      chains.

PMID- 28493463
TI  - Main predators of insect pests: screening and evaluation through comprehensive
      indices.
AB  - BACKGROUND: Predatory natural enemies play key functional roles in integrated
      pest management. However, the screening and evaluation of the main predators of
      insect pests has seldom been reported in the field. Here, we employed
      comprehensive indices for evaluating the predation of a common pest (Ectropis
      obliqua) by nine common spider species in Chinese tea plantations. RESULTS: We
      established the relative dominance of the spider species and their phenological
      overlap with the pest species, and analyzed DNA from the nine spider species
      using targeted real-time quantitative polymerase chain reaction to identify the
      residual DNA of E. obliqua. The predation rates and predation numbers per
      predator were estimated by the positive rates of target fragments and the
      residual minimum number of E. obliqua in predators' guts, respectively. The
      results showed that only four spider species preyed on E. obliqua, and the order
      of potential of the spiders to control E. obliqua from greatest to smallest was
      Neoscona mellotteei, Xysticus ephippiatus, Evarcha albaria and Coleosoma
      octomaculatum by the Z-score method. CONCLUSION: The orb-weaving spider N.
      mellotteei has the maximum potential as a biological control agent of E. obliqua
      in an integrated pest management strategy. An approach of screening and
      evaluating main predators of insect pests through comprehensive indices was
      preliminarily established. (c) 2017 Society of Chemical Industry.

PMID- 28493464
TI  - First-trimester ultrasound screening for trisomy 21 based on maternal age, fetal
      nuchal translucency, and different methods of ductus venosus assessment.
AB  - OBJECTIVE: To examine whether combining the dichotomous assessment of the a-wave
      and the ductus venosus (DV) pulsatility index for veins (PIV) measurement
      improves first-trimester screening performance. METHODS: Retrospective study
      performed at the University Hospital of Tuebingen based on singleton pregnancies
      that underwent first-trimester screening including DV flow assessment. In each
      case, the risk of trisomy 21 was calculated based on maternal age, fetal nuchal
      translucency, and DV flow either as dichotomous classification of the a-wave, as
      measurement of the DV PIV, or both. RESULTS: There were 5280 euploid fetuses and
      127 fetuses with trisomy 21. The DV a-wave was reversed in 2.3% and 66.1% in the
      euploid and trisomy 21 cases, respectively. The DV PIV measurements were above
      the 95th percentile in 8.3% and 77.2% the euploid and trisomy 21 cases,
      respectively. For a false positive rate of 3%, the detection rate for trisomy 21
      based on maternal age, fetal NT, and DV flow is about 87% irrespective of whether
      DV is examined as a continuous or dichotomous variable. The combination of both
      resulted in a small decrease at 3% false positive rate. CONCLUSION: Assessment of
      the DV a-wave and the DV PIV result in similar DRs. Combining these two
      approaches does not appear to improve their individual screening performance. (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28493465
TI  - Changes in right ventricular function assessed by echocardiography in dog models
      of mild RV pressure overload.
AB  - BACKGROUND: The assessment of hemodynamic change by echocardiography is
      clinically useful in patients with pulmonary hypertension. Recently, mild
      elevation of the mean pulmonary arterial pressure (PAP) has been shown to be
      associated with increased mortality. However, changes in the echocardiographic
      indices of right ventricular (RV) function are still unknown. The objective of
      this study was to validate the relationship between echocardiographic indices of
      RV function and right heart catheterization variables under a mild RV pressure
      overload condition. METHODS AND RESULTS: Echocardiography and right heart
      catheterization were performed in dog models of mild RV pressure overload induced
      by thromboxane A2 analog (U46619) (n=7). The mean PAP was mildly increased
      (19.3+/-1.1 mm Hg), and the cardiac index was decreased. Most echocardiographic
      indices of RV function were significantly impaired even under a mild RV pressure
      overload condition. Multivariate analysis revealed that the RV free wall
      longitudinal strain (RVLS), standard deviation of the time-to-peak longitudinal
      strain of RV six segments (RV-SD) by speckle-tracking echocardiography, and Tei
      index were independent echocardiographic predictors of the mean PAP (free wall
      RVLS, beta=-0.60, P<.001; RV-SD, beta=0.40, P=.011), pulmonary vascular
      resistance (free wall RVLS, beta=-0.39, P=.020; RV-SD, beta=0.47, P=.0086; Tei
      index, beta=0.34, P=.047), and cardiac index (Tei index, beta=-0.65, P<.001).
      CONCLUSIONS: Free wall RVLS, RV-SD, and Tei index are useful for assessing the
      hemodynamic change under a mild RV pressure overload condition.

PMID- 28493466
TI  - 'It's Fast, It's Quick, It Stops Me Being Sick': How to influence preparation of
      opioid tablets for injection.
AB  - INTRODUCTION AND AIMS: Injection of pharmaceutical opioids (PO) among people who
      inject drugs has increased in many countries. The common method for preparing PO
      tablets for injection uses heat, resulting in greater particulate matter and
      therefore increased risk of local infection risk and damage to veins and organs.
      A cold preparation process has fewer risks, but this preparation method is not
      commonly used. This study seeks to explore how people who inject PO learn to
      prepare injections and how health promotion efforts could influence practice.
      DESIGN AND METHODS: Between March and December 2013, qualitative interviews were
      undertaken with 33 clients of Sydney's Medically Supervised Injecting Centre who
      inject PO tablets regarding sources of knowledge and current preparation methods
      for injection of POs. RESULTS: Overwhelmingly, the most commonly reported source
      of knowledge around injection of tablets was others who inject. Most participants
      reported heating the solution as the quickest way to administer the drug.
      Attitudes to the use of wheel filters varied, with some participants reporting
      that they would use the filters if they were shown how, while others reported a
      number of barriers to using filters, including complexity of use. DISCUSSION AND
      CONCLUSIONS: Harnessing the power of social connections may provide avenues for
      education about safer injecting of tablets, including the use of wheel filters.
      Further work is required to debunk myths about the relative potencies of cold
      versus hot drug solution. Collaborations between harm reduction workers and peer
      workers would assist in knowledge dissemination regarding safer injecting
      practices.

PMID- 28493467
TI  - Discovery of EGF Receptor Inhibitors That Are Selective for the d746
      750/T790M/C797S Mutant through Structure-Based de Novo Design.
AB  - Next-generation epidermal growth factor receptor (EGFR) inhibitors against the
      d746-750/T790M/C797S mutation were discovered through two-track virtual screening
      and de novo design. A number of nanomolar inhibitors were identified using 2-aryl
      4-aminoquinazoline as the molecular core and the modified binding energy function
      involving a proper dehydration term, which provides important structural insight
      into the key principles for high inhibitory activities against the d746
      750/T790M/C797S mutant. Furthermore, some of these EGFR inhibitors showed a
      greater than 1000-fold selectivity for the d746-750/T790M/C797S mutant over the
      wild type, as well as nanomolar activity against the mutant.

PMID- 28493468
TI  - Insight into the success of whitefly biological control using parasitoids:
      evidence from the Eretmocerus warrae-Trialeurodes vaporariorum system.
AB  - BACKGROUND: Mechanisms behind the success and failure of whitefly biological
      control using parasitoids are largely unknown. Here we use the Eretmocerus warrae
      greenhouse whitefly system to investigate how the fluctuating density of the
      parasitoid and its host affects three key parasitoid fitness parameters, host
      searching, host feeding and parasitization, providing critical knowledge for
      evaluation and development of whitefly biological control programmes. This is the
      first such study in a parasitoid-whitefly system. RESULTS: Models used and
      developed here show that (1) both host feeding and parasitism fit a type II
      functional response; (2) overall parasitoid-caused whitefly mortality
      significantly increases with growing density of both organisms and the parasitoid
      density has a significantly more positive effect; (3) with a pro-synovigenic
      nature, E. warrae allocate significantly more resources to parasitization than to
      host feeding activity in low whitefly density and high parasitoid density; and
      (4) low mutual interference among searching parasitoids encourages parasitoid
      aggregation on host patches of high density. CONCLUSION: Regardless of greenhouse
      whitefly density, the pest can be effectively controlled by release of E. warrae.
      Our study provides insight into the success of whitefly biological control
      programmes using the parasitoid augmentation approach. Models used and developed
      here can also be employed to evaluate biological control programmes for other
      parasitoid-whitefly systems. (c) 2017 Society of Chemical Industry.

PMID- 28493469
TI  - Nature-Inspired Synthesis of Nanostructured Electrocatalysts through
      Mineralization of Calcium Carbonate.
AB  - Biomineralization is a biogenic process that produces elaborate inorganic and
      organic hybrid materials in nature. Inspired by the natural process, this study
      explored a new mineralization approach to create nanostructured CaCO3 films
      composed of amorphous CaCO3 hemispheres by using catechol-rich polydopamine (PDA)
      as a biomimetic mediator. The thus synthesized biomimetic CaCO3 was successfully
      transformed to nanostructured films of metal-oxide minerals, such as FeOOH, CoCO3
      , NiCO3 , and MnOOH, through a simple procedure. The CaCO3 -templated metal-oxide
      minerals functioned as efficient electrocatalysts; a CaCO3 -templated cobalt
      phosphate (nanoCoPi) film exhibited high stability as a water-oxidation
      electrocatalyst with a current density of 1.5 mA cm-2 . The nanostructure of
      nanoCoPi, consisting of individual nanoparticles (~70 nm) and numerous internal
      pores (BET surface area: 3.17 m2  g-1 ), facilitated an additional charge
      transfer pathway from the electrode to individual active sites of the catalyst.
      This work demonstrates a plausible strategy for facile and green synthesis of
      nanostructured electrocatalysts through biomimetic CaCO3 mineralization.

PMID- 28493470
TI  - Prognostic significance of serum immunoglobulin paraprotein in patients with
      diffuse large B cell lymphoma.

PMID- 28493471
TI  - What role does the stress response have in congestive heart failure?
AB  - This review is concerned with cardiac malfunction as a result of an imbalance in
      protein proteostasis, the homeostatic balance between protein removal and
      regeneration in a long remodeling process involving the endoplasmic reticulum
      (ER) and the unfolded protein response (UPR). The importance of this is of
      special significance with regard to cardiac function as a high energy requiring
      muscular organ that has a high oxygen requirement and is highly dependent on
      mitochondria. The importance of mitochondria is not only concerned with high
      energy dependence on mitochondrial electron transport, but it also has a role in
      the signaling between the mitochondria and the ER under stress. Proteins made in
      the ER are folded as a result of sulfhydryl groups (-SH) and attractive and
      repulsive reactions in the tertiary structure. We discuss how this matters with
      respect to an imbalance between muscle breakdown and repair in a stressful
      environment, especially as a result of oxidative and nitrosative byproducts of
      mitochondrial activity. The normal repair is a remodeling, but under this
      circumstance, the cell undergoes or even lysosomal "self eating" autophagy, or
      even necrosis instead of apoptosis. We shall discuss the relationship of the UPR
      pathway to chronic congestive heart failure (CHF).

PMID- 28493472
TI  - Turf wars: exploring splenomegaly in sickle cell disease in malaria-endemic
      regions.
AB  - Sickle cell disease (SCD) is a group of recessively inherited disorders of
      erythrocyte function that presents an ongoing threat to reducing childhood and
      adult morbidity and mortality around the world. While decades of research have
      led to improved survival for SCD patients in wealthy countries, survival remains
      dismal in low- and middle-income countries. Much of the early mortality
      associated with SCD is attributed to increased risk of infections due to early
      loss of splenic function. In the West, bacterial infections with encapsulated
      organisms are a primary concern. In sub-Saharan Africa, where the majority of
      infants with SCD are born, the same is true. However malaria presents an
      additional threat to survival. The search for factors that define variability in
      sickle cell phenotypes should include environmental modifiers, such as malaria.
      Further exploration of this relationship could lead to novel strategies to reduce
      morbidity and mortality attributable to infections. In this review, we explore
      the interactions between SCD, malaria and the spleen to better understand how
      splenomegaly and splenic (dys)function may co-exist in patients with SCD living
      in malaria-endemic areas.

PMID- 28493474
TI  - Effects of heat stress and probiotic supplementation on protein functionality and
      oxidative stability of ground chicken leg meat during display storage.
AB  - BACKGROUND: The present study aimed to evaluate the effects of heat stress and
      probiotic supplementation on protein functionality and oxidative stability of
      ground chicken leg during display storage. Two hundred and forty, 1-day-old male
      chicks (5 birds per pen) were subjected to four treatments in a 2 (thermoneutral
      condition at 21  degrees C and cyclic heat stress at 32-21-32  degrees C for 10 h
      day-1 ) * 2 (regular diet with 0 or 0.25 g kg-1 Bacillus subtilis) factorial
      design. Chickens were harvested at day 46, and pairs of whole legs were collected
      at 1 day postmortem. The chicken legs were deboned, ground, tray-packaged with
      oxygen-permeable film, and displayed for 3 days. RESULTS: Heat stress and
      probiotic supplementation had no impact on pH, water-holding capacity, color,
      protein functionality, lipid lipolysis and lipid/protein oxidation stability (P >
      0.05). Display storage increased the pH and lipid oxidation of ground chicken
      legs (P < 0.05). In addition, protein oxidation occurred during display storage,
      as determined via an increased carbonyl group (P = 0.0109) and reduced thiol
      group (P < 0.0001). CONCLUSION: The results of the present study indicate that
      chronic heat stress and probiotic supplementation had no practical adverse impact
      on protein functionality and oxidative stability of ground chicken leg meat. (c)
      2017 Society of Chemical Industry.

PMID- 28493473
TI  - Dysregulation of mitochondrial bioenergetics and quality control by HIV-1 Tat in
      cardiomyocytes.
AB  - Cardiovascular disease remains a leading cause of morbidity and mortality in HIV
      positive patients, even in those whose viral loads are well controlled with
      antiretroviral therapy. However, the underlying molecular events responsible for
      the development of cardiac disease in the setting of HIV remain unknown. The HIV
      encoded Tat protein plays a critical role in the activation of HIV gene
      expression and profoundly impacts homeostasis in both HIV-infected cells and
      uninfected cells that have taken up released Tat via a bystander effect. Since
      cardiomyocyte function, including excitation-contraction coupling, greatly
      depends on energy provided by the mitochondria, in this study, we performed a
      series of experiments to assess the impact of Tat on mitochondrial function and
      bioenergetics pathways in a primary cell culture model derived from neonatal rat
      ventricular cardiomyocytes (NRVCs). Our results show that the presence of Tat in
      cardiomyocytes is accompanied by a decrease in oxidative phosphorylation, a
      decline in the levels of ATP, and an accumulation of reactive oxygen species
      (ROS). Tat impairs the uptake of mitochondrial Ca2+ ([Ca2+ ]m ) and the
      electrophysiological activity of cardiomyocytes. Tat also affects the protein
      clearance pathway and autophagy in cardiomyocytes under stress due to hypoxia
      reoxygenation conditions. A reduction in the level of ubiquitin along with
      dysregulated degradation of autophagy proteins including SQSTM1/p62 and a
      reduction of LC3 II were detected in cardiomyocytes harboring Tat. These results
      suggest that, by targeting mitochondria and protein quality control, Tat
      significantly impacts bioenergetics and autophagy resulting in dysregulation of
      cardiomyocyte health and homeostasis.

PMID- 28493475
TI  - Change of left ventricular "rigid body rotation" during dipyridamole-induced
      vasodilation: A case from the three-dimensional speckle tracking
      echocardiographic MAGYAR-Stress Study.
AB  - A patient with previous coronary stenting presented with stable angina and
      positive exercise treadmill test. Echocardiography with three-dimensional speckle
      tracking demonstrated left ventricular rigid body rotation (near absence of left
      ventricular twist), whose characteristics changed dramatically during
      dipyridamole-induced vasodilatation. (c) 2017 Wiley Periodicals, Inc. J Clin
      Ultrasound 46:152-156, 2018.

PMID- 28493476
TI  - First report on free and covalently bound microcystins in fish and bivalves from
      Vietnam: Assessment of risks to humans.
AB  - The free and covalently bound microcystins (MCs) in 3 fish and 2 bivalves from
      the Dau Tieng Reservoir in Vietnam were investigated for the first time in the
      present study. The results showed that all species were contaminated with MCs.
      Our findings indicate that eating the muscle of fish from the Dau Tieng Reservoir
      is safe but that eating the bivalves is not safe during toxic cyanobacterial
      bloom episodes. Environ Toxicol Chem 2017;36:2953-2957. (c) 2017 SETAC.

PMID- 28493477
TI  - Superficial basal cell carcinoma: A comparison of superficial only subtype with
      superficial combined with other subtypes by age, sex and anatomic site in 3150
      cases.
AB  - BACKGROUND: Basal cell carcinoma (BCC) may present as superficial subtype alone
      (sBCC) or superficial combined with other subtypes. The objective of this study
      was to compare sBCC without or with other BCC subtypes by age, sex and anatomic
      site. METHODS: We retrospectively collected superficial BCC with the above
      characteristics from an Australian center during 2009 to 2014. RESULTS: We
      recorded 1528 sBCC and 1622 superficial BCC combined with other BCC subtype
      cases. Males numbered 2007 and females 1140. On males, head sites (forehead,
      cheek, nose and ear combined) compared to limb plus trunk sites displayed a
      higher incidence of superficial BCC combined with either nodular and or
      aggressive BCC subtypes (OR 13.15 CI 95% 8.9-19.5 P < .0001). On females a
      similar comparison also found a higher incidence of superficial BCC combined with
      solid subtype BCC on head sites compared to trunk and limb sites (OR 9.66 CI 95%
      5.8-16.1 P < .0001). CONCLUSION: Superficial BCC alone is more likely on younger
      females on trunk and limb sites. Small partial biopsies reported as sBCC may miss
      other BCC subtypes present with higher risk on facial sites for males and
      females. Males had smaller proportions of superficial only subtype BCC on facial
      and ear sites compared to females.

PMID- 28493478
TI  - Three-dimensional models of the segmented human fetal brain generated by magnetic
      resonance imaging.
AB  - Recent advances in imaging technology have enabled us to obtain more detailed
      images of the human fetus in a nondestructive and noninvasive manner. Through
      detailed images, elaborate three-dimensional (3D) models of the developing brain
      can be reconstructed. The segmentation of the developing brain has been
      determined by serial sections. Therefore, in this study, we attempted to develop
      a 3D model of the fetal brain using magnetic resonance image (MRI). MR images
      from 19 specimens (11 embryonic specimens and eight fetal specimens from 5.2 to
      225 mm in crown rump length) were used to reconstruct 3D models of regionalized
      developing brains. From this analysis, we succeeded in registering a maximum of
      nine landmarks on MR images and reconstructing 19 sequential models of the
      regionalized developing brain. To confirm the validity of the landmarks, we also
      compared our results with three serial sections from the Kyoto Collection; the
      same morphological characteristics were observed on both serial sections and MRI.
      The morphological minutiae could be found on MR images, and regionalized models
      of the developing brain could be reconstructed. These results will be useful for
      clinical diagnosis of living fetuses in utero.

PMID- 28493479
TI  - Expectancies mediate the relationship between perceived injustice and return to
      work following whiplash injury: A 1-year prospective study.
AB  - BACKGROUND: Emerging evidence suggests that perceived injustice is a risk factor
      for work disability in individuals with whiplash injury. At present, however,
      little is known about the processes by which perceived injustice impacts on
      return to work. The purpose of this study was to examine whether expectancies
      mediated the relationship between perceived injustice and return to work in
      patients with whiplash injury. METHOD: One hundred and fifty-two individuals (81
      men, 71 women) with a primary diagnosis of whiplash injury completed self-report
      measures of pain intensity, perceived injustice and return-to-work expectancies
      following admission to a rehabilitation programme. Work status was assessed 1
      year after discharge. RESULTS: Consistent with previous research, high scores on
      a measure of perceived injustice were associated with prolonged work disability.
      Results indicated that high perceptions of injustice were associated with low
      return-to-work expectancies. Causal mediation analyses revealed that expectancies
      fully mediated the relationship between perceived injustice and return to work.
      CONCLUSION: The findings suggest that intervention techniques designed to target
      expectancies could improve return-to-work outcomes in patients with whiplash
      injury. Discussion addresses the processes by which expectancies might impact on
      return-to-work outcomes and the manner in which negative return-to-work
      expectancies might be modified through intervention. SIGNIFICANCE: The study
      confirms that expectancies are the mechanism through which perceived injustice
      impacts return to work following whiplash injury. The findings suggest that
      interventions designed to specifically target return-to-work expectancies might
      improve rehabilitation outcomes in patients with whiplash injury.

PMID- 28493480
TI  - Sonographic findings of IgG4-related disease of the salivary glands: Case report
      and review of the literature.
AB  - IgG4-related disease is a relatively newly described entity with findings that
      historically have been confused with a variety of other diseases with markedly
      different treatments and prognoses, including Sjogren's syndrome and MALT
      lymphoma. We present a case of IgG4-related disease of the salivary glands and
      review the literature on sonographic findings of IgG4-related disease. By
      connecting sonographic features of IgG4 disease with common ancillary features of
      IgG4 disease in other sites (pancreas, hilar lymph nodes, biliary tree, thyroid,
      and retroperitoneum), radiologists can play a pivotal role in the early diagnosis
      and identification of IgG4-related disease. (c) 2017 Wiley Periodicals, Inc. J
      Clin Ultrasound 46:73-77, 2018.

PMID- 28493481
TI  - Hospital and Health Insurance Markets Concentration and Inpatient Hospital
      Transaction Prices in the U.S. Health Care Market.
AB  - OBJECTIVE: To examine the effects of hospital and insurer markets concentration
      on transaction prices for inpatient hospital services. DATA SOURCES: Measures of
      hospital and insurer markets concentration derived from American Hospital
      Association and HealthLeaders-InterStudy data are linked to 2005-2008 inpatient
      administrative data from Truven Health MarketScan Databases. STUDY DESIGN: Uses a
      reduced-form price equation, controlling for cost and demand shifters and
      accounting for possible endogeneity of market concentration using instrumental
      variables (IV) technique. PRINCIPAL FINDINGS: The findings suggest that greater
      hospital concentration raises prices, whereas greater insurer concentration
      depresses prices. A hypothetical merger between two of five equally sized
      hospitals is estimated to increase hospital prices by about 9 percent (p < .001).
      A similar merger of insurers would depress prices by about 15.3 percent (p <
      .001). Over the 2003-2008 periods, the estimates imply that hospital
      consolidation likely raised prices by about 2.6 percent, while insurer
      consolidation depressed prices by about 10.8 percent. Additional analysis using
      longer panel data and applying hospital fixed effects confirms the impact of
      hospital concentration on prices. CONCLUSION: The findings provide support for
      strong antitrust enforcement to curb rising hospital service prices and health
      care costs.

PMID- 28493483
TI  - Preoperative imaging and prediction of oesophageal conduit necrosis after
      oesophagectomy for cancer.
AB  - BACKGROUND: Oesophageal conduit necrosis following oesophagectomy is a rare but
      life-threatening complication. The present study aimed to assess the impact of
      coeliac axis stenosis on outcomes after oesophagectomy for cancer. METHODS: The
      study included consecutive patients who had an Ivor Lewis procedure with curative
      intent for middle- and lower-third oesophageal cancer at two tertiary referral
      centres. All patients underwent preoperative multidetector CT with arterial phase
      to detect coeliac axis stenosis. The coeliac artery was classified as normal,
      with extrinsic stenosis due to a median arcuate ligament or with intrinsic
      stenosis caused by atherosclerosis. RESULTS: Some 481 patients underwent an Ivor
      Lewis procedure. Of these, ten (2.1 per cent) developed oesophageal conduit
      necrosis after surgery. Coeliac artery evaluation revealed a completely normal
      artery in 431 patients (91.5 per cent) in the group without conduit necrosis and
      in one (10 per cent) with necrosis (P < 0.001). Extrinsic stenosis of the coeliac
      artery due to a median arcuate ligament was found in two patients (0.4 per cent)
      without conduit necrosis and five (50 per cent) with necrosis (P < 0.001).
      Intrinsic stenosis of the coeliac artery was found in 11 (2.3 per cent) and eight
      (80 per cent) patients respectively (P < 0.001). Eight patients without (1.7 per
      cent) and five (50 per cent) with conduit necrosis had a single and thin left
      gastric artery (P < 0.001). CONCLUSION: This study suggests that oesophageal
      conduit necrosis after oesophagectomy for cancer may be due to pre-existing
      coeliac axis stenosis.

PMID- 28493482
TI  - Emergence of cytochrome bc complexes in the context of photosynthesis.
AB  - The cytochrome bc (cyt bc) complexes are involved in Q-cycling; they oxidize
      membrane quinols by high-potential electron acceptors, such as cytochromes or
      plastocyanin, and generate transmembrane proton gradient. In several prokaryotic
      lineages, and also in plant chloroplasts, the catalytic core of the cyt bc
      complexes is built of a four-helical cytochrome b (cyt b) that contains three
      hemes, a three-helical subunit IV, and an iron-sulfur Rieske protein (cytochrome
      b6 f-type complexes). In other prokaryotic lineages, and also in mitochondria,
      the cyt b subunit is fused with subunit IV, yielding a seven- or eight-helical
      cyt b with only two hemes (cyt bc1 -type complexes). Here we present an updated
      phylogenomic analysis of the cyt b subunits of cyt bc complexes. This analysis
      provides further support to our earlier suggestion that (1) the ancestral version
      of cyt bc complex contained a small four-helical cyt b with three hemes similar
      to the plant cytochrome b6 and (2) independent fusion events led to the formation
      of large cyts b in several lineages. In the search for a primordial function for
      the ancestral cyt bc complex, we address the intimate connection between the cyt
      bc complexes and photosynthesis. Indeed, the Q-cycle turnover in the cyt bc
      complexes demands high-potential electron acceptors. Before the Great Oxygenation
      Event, the biosphere had been highly reduced, so high-potential electron
      acceptors could only be generated upon light-driven charge separation. It appears
      that an ancestral cyt bc complex capable of Q-cycling has emerged in conjunction
      with the (bacterio)chlorophyll-based photosynthetic systems that continuously
      generated electron vacancies at the oxidized (bacterio)chlorophyll molecules.

PMID- 28493485
TI  - Comprehensive characterization of the acute and chronic toxicity of the
      neonicotinoid insecticide thiamethoxam to a suite of aquatic primary producers,
      invertebrates, and fish.
AB  - Thiamethoxam is a neonicotinoid insecticide used widely in agriculture to control
      a broad spectrum of chewing and sucking insect pests. Recent detection of
      thiamethoxam in surface waters has raised interest in characterizing the
      potential impacts of this insecticide to aquatic organisms. We report the results
      of toxicity testing (acute and chronic) conducted under good laboratory practices
      for more than 30 freshwater species (insects, molluscs, crustaceans, algae,
      macrophytes, and fish) and 4 marine species (an alga, a mollusc, a crustacean,
      and a fish). As would be anticipated for a neonicotinoid, aquatic primary
      producers and fish were the least sensitive organisms tested, with acute median
      lethal and effect concentrations (LC50/EC50) observed to be >=80 mg/L in all
      cases, which far exceeds surface water exposure concentrations. Tested molluscs,
      worms, and rotifers were similarly insensitive (EC50 >= 100 mg/L), except for
      Lumbriculus sp., with an EC50 of 7.7 mg/L. In general, insects were the most
      sensitive group in the study, with most acute EC50 values < 1 mg/L. However, the
      crustaceans Asellus aquaticus and Ostracoda exhibited a sensitivity similar to
      that of insects (acute EC50 < 1 mg/L), and the midge larvae Chaoborus sp. were
      relatively insensitive compared with other insects (EC50 > 5.5 mg/L). The most
      sensitive chronic response was for Chironomus riparius, with a 30-d no-observed
      effect concentration (NOEC; emergence) of 0.01 mg/L. Observed toxicity to the
      tested marine organisms was comparable to that of freshwater species. We used the
      reported data to construct species sensitivity distributions for thiamethoxam, to
      calculate 5% hazard concentrations (HC5s) for acute data (freshwater
      invertebrates), and compared these with measured concentrations from relevant
      North American surface waters. Overall, based on acute toxicity endpoints, the
      potential acute risk to freshwater organisms was found to be minimal (likelihood
      of exceeding HC5s < 1%). Environ Toxicol Chem 2017;36:2838-2848. (c) 2017 The
      Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals,
      Inc. on behalf of SETAC.

PMID- 28493484
TI  - Cytoplasmic overexpression of RNA-binding protein HuR is a marker of poor
      prognosis in meningioma, and HuR knockdown decreases meningioma cell growth and
      resistance to hypoxia.
AB  - HuR regulates cytoplasmic mRNA stability and translatability, and the HuR
      expression level has been shown to correlate with poor disease outcome in several
      cancer types; however, the prognostic value and potential pro-oncogenic
      properties of HuR in meningioma remain unclear. Thus, in the present study, we
      analysed 85 meningioma tissue samples to establish the relationship between HuR
      expression, tumour cell proliferation, and/or patient survival. In addition, we
      examined the anti-proliferative effects of HuR knockdown in two meningioma cell
      lines (IOMM-Lee and Ben-Men-1) and conducted transcriptome-wide analyses (IOMM
      Lee cells) to elucidate the molecular consequences of HuR knockdown. The results
      of the present study showed HuR cytoplasmic expression to correlate positively
      with tumour grade (p = 1.2 * 10-8 ) and negatively with progression-free and
      overall survival (p = 0.01) time in human meningioma tissues. In vitro, siHuR
      induced HuR knockdown was shown to reduce the growth of both Ben-Men-1 (p = 2 *
      10-8 ) and IOMM-Lee (p = 4 * 10-9 ) cells. Transcriptome analyses revealed HuR
      knockdown in IOMM-Lee cells to deregulate the HIF1A signalling pathway (p = 1.5 *
      10-6 ) and to up-regulate the expression of genes essential for the assembly of
      the cytoplasmic mRNA processing body, global genome nucleotide-excision repair,
      poly(A)-specific ribonuclease activity, the positive regulation of apoptosis and
      of cell cycle arrest, and the negative regulation of RNA splicing [p(FDR) <
      0.001]. Interestingly, HuR knockdown under hypoxic culture conditions further
      potentiated the effects of HuR knockdown on cell growth, apoptosis, and HIF1A
      expression. We thus conclude that cytoplasmic HuR expression is a marker of poor
      prognosis in meningioma and that HuR is a promising potential therapeutic target
      for use in tumours refractory to standard therapies. Copyright (c) 2017
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 28493486
TI  - Pansteatitis in polluted Olifants River impoundments: nutritional perspectives on
      fish in a eutrophic lake, Lake Loskop, South Africa.
AB  - This study compares the aetiology of pansteatitis in Lake Loskop, relative to two
      other impoundments along the Olifants River. Macroscopic and microscopic
      pathology, age determination and analysis of stomach content, fatty acids and
      stable isotopes explain the high prevalence of pansteatitis in Oreochromis
      mossambicus (Peters) and several other species in Lake Loskop. All the dietary
      indicator comparisons between pansteatitis-affected and healthy fish fail to
      support a systemic cause. Pansteatitis in Lake Loskop was linked to size and
      weight of O. mossambicus, but not to ontogenic age. Fish in Lake Loskop showed
      abnormally high omega-3 to omega-6 fatty acid ratios normally only found in
      marine fish with no significant difference in degree of assimilation of these
      fatty acids between pansteatitis-affected and healthy fish. This explains the
      vulnerability to, but not the occurrence of, pansteatitis. As a cause for the
      pansteatitis, these results point towards sporadic vitamin E-depleting trigger
      events, known sporadic fish die-off occurrences that provide surviving fish with
      a rich source of rancid fats on which to scavenge. The mechanism ties
      pansteatitis to eutrophication and trophic cascade effects, the intrinsic drivers
      of the disease and suggests an adaptive management strategy that might be applied
      by relevant conservation authorities.

PMID- 28493487
TI  - Effect of starvation and refeeding on the hepatopancreas of whiteleg shrimp
      Penaeus vannamei (Boone) using computer-assisted image analysis.
AB  - Under normal farming conditions, shrimp can experience starvation periods
      attributable to disease outbreaks or adverse environmental conditions. Starvation
      leads to significant morphological changes in the hepatopancreas (HP), being the
      main organ for absorption and storage of nutrients. In the literature, limited
      research has described the effect on the HP of periods of starvation followed by
      refeeding and none in whiteleg shrimp (Penaeus vannamei) using computer-assisted
      image analysis (CAIA). This study describes the effect of starvation and
      starvation followed by refeeding on the HP of whiteleg shrimp using CAIA.
      Visiopharm(r) software was used to quantify the following morphological
      parameters, measured as ratio to the total tissue area (TLA): total lumen area
      (TLA:TTA), haemocytic infiltration area in the intertubular spaces (HIA:TTA), B
      cell vacuole area (VBA:TTA), lipid droplet area within R cells (LDA:TTA) and F
      cell area (FCA:TTA). Significant changes were measured for HIA:TTA and LDA:TTA
      during starvation (increase in HIA:TTA associated with decrease in LDA:TTA) and
      starvation followed by refeeding (decrease in HIA:TTA associated with increase in
      LDA:TTA). In the future, HIA:TTA and LDA:TTA have the potential to be used in a
      pre-emptive manner to monitor the health of the HP, facilitate early diagnosis of
      diseases and study the pathophysiology of the organ.

PMID- 28493488
TI  - Seasonality of odonate-mediated methylmercury flux from permanent and
      semipermanent ponds and potential risk to red-winged blackbirds (Agelaius
      phoeniceus).
AB  - Methylmercury (MeHg) is an aquatic contaminant that can be transferred to
      terrestrial predators by emergent aquatic insects such as odonates (damselflies
      and dragonflies). We assessed the effects of month and pond permanence on odonate
      mediated MeHg flux (calculated as emergent odonate biomass * MeHg concentration)
      in 10 experimental ponds and the potential risk to nestling red-winged blackbirds
      (Agelaius phoeniceus) posed by consuming MeHg-contaminated odonates. Emergent
      odonates were collected weekly from permanent ponds with bluegill (Lepomis
      macrochirus; n = 5) and semipermanent ponds without fish (n = 5) over an 8-mo
      period (January-August 2015). The MeHg flux from damselflies, aeshnid
      dragonflies, and libellulid dragonflies began in March and peaked in April, May,
      and June, respectively, and then declined throughout the rest of the summer.
      Odonate-mediated MeHg flux from semipermanent ponds without fish was greater than
      that from permanent ponds with fish. Nesting of red-winged blackbirds overlapped
      with peak odonate emergence and odonate-mediated MeHg flux. Because their diet
      can be dominated by damselflies and dragonflies, we tested the hypothesis that
      MeHg-contaminated odonates may pose a health risk to nestling red-winged
      blackbirds. Concentrations of MeHg in odonates exceeded wildlife values (the
      minimum odonate MeHg concentrations causing physiologically significant doses in
      consumers) for nestlings, suggesting that MeHg-contaminated odonates can pose a
      health risk to nestling red-winged blackbirds. Environ Toxicol Chem 2017;36:2833
      2837. (c) 2017 SETAC.

PMID- 28493490
TI  - The protective effect of humic-rich substances on atypical Aeromonas salmonicida
      subsp. salmonicida infection in common carp (Cyprinus carpio L.).
AB  - When challenged with atypical Aeromonas salmonicida subsp. salmonicida, exposure
      of the common carp (Cyprinus carpio L.) to different humic-rich compounds
      resulted in a significant reduction in infection rates. Specifically, in fish
      exposed to (i) humic-rich water and sludge from a recirculating system, (ii) a
      synthetic humic acid, and (iii) a Leonardite-derived humic-rich extract,
      infection rates were reduced to 14.9%, 17.0% and 18.8%, respectively, as compared
      to a 46.8% infection rate in the control treatment. An additional set of
      experiments was performed to examine the effect of humic-rich components on the
      growth of the bacterial pathogen. Liquid culture medium supplemented with either
      humic-rich water from the recirculating system, the synthetic humic acid or the
      Leonardite humic-rich extract resulted in a growth reduction of 41.1%, 45.2% and
      61.6%, respectively, as compared to the growth of the Aeromonas strain in medium
      devoid of humic substances. Finally, in a third set of experiments it was found
      that while the innate immune system of the carps was not affected by their
      exposure to humic-rich substances, their acquired immune system was affected.
      Fish, immunized against bovine serum albumin, displayed elevated antibody titres
      as compared to immunized carps which were not exposed to the various sources of
      humic substances.

PMID- 28493489
TI  - A path model of different forms of impulsivity with externalizing and
      internalizing psychopathology: Towards greater specificity.
AB  - OBJECTIVES: A growing empirical literature indicates that emotion-related
      impulsivity (compared to impulsivity that is unrelated to emotion) is
      particularly relevant for understanding a broad range of psychopathologies.
      Recent work, however, has differentiated two forms of emotion-related
      impulsivity: A factor termed Pervasive Influence of Feelings captures tendencies
      for emotions (mostly negative emotions) to quickly shape thoughts, and a factor
      termed Feelings Trigger Action captures tendencies for positive and negative
      emotions to quickly and reflexively shape behaviour and speech. This study used
      path modelling to consider links from emotion-related and non-emotion-related
      impulsivity to a broad range of psychopathologies. DESIGN AND METHODS:
      Undergraduates completed self-report measures of impulsivity, depression,
      anxiety, aggression, and substance use symptoms. RESULTS: A path model (N = 261)
      indicated specificity of these forms of impulsivity. Pervasive Influence of
      Feelings was related to anxiety and depression, whereas Feelings Trigger Action
      and non-emotion-related impulsivity were related to aggression and substance use.
      CONCLUSIONS: The findings of this study suggest that emotion-relevant impulsivity
      could be a potentially important treatment target for a set of psychopathologies.
      PRACTITIONER POINTS: Recent work has differentiated two forms of emotion-related
      impulsivity. This study tests a multivariate path model linking emotion-related
      and non-emotion-related impulsivity with multiple forms of psychopathology.
      Impulsive thoughts in response to negative emotions were related to anxiety and
      depression. Impulsive actions in response to emotions were related to aggression
      and substance use, as did non-emotion-related impulsivity. The study was limited
      by the reliance on self-report measures of impulsivity and psychopathology. There
      is a need for longitudinal work on how these forms of impulsivity predict the
      onset and course of psychopathology.

PMID- 28493491
TI  - High doses of recombinant mannan-binding lectin inhibit the binding of influenza
      A(H1N1)pdm09 virus with cells expressing DC-SIGN.
AB  - The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human
      health. Low doses of mannan-binding lectin (MBL) (<1 MUg/mL) were shown not to
      protect against influenza A(H1N1)pdm09 infection. However, the effect of high
      doses of MBL has not been investigated. Dendritic cell-specific intercellular
      adhesion molecule-3 grabbing non-integrin (DC-SIGN) has been proposed as an
      alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined
      the expression of DC-SIGN on DCs as well as on acute monocytic leukemia cell
      line, THP-1. High doses of recombinant or human MBL inhibited binding of
      influenza A(H1N1)pdm09 to both these cell types in the presence of complement
      derived from bovine serum. Further, anti-DC-SIGN monoclonal antibody inhibited
      binding of influenza A(H1N1)pdm09 to both DC-SIGN-expressing DCs and THP-1 cells.
      This study demonstrates that high doses of MBL can inhibit binding of influenza
      A(H1N1)pdm09 virus to DC-SIGN-expressing cells in the presence of complement. Our
      results suggest that DC-SIGN may be an alternative receptor for influenza
      A(H1N1)pdm09 virus.

PMID- 28493492
TI  - Dehydroacetic Acid Derivatives Bearing Amide or Urea Moieties as Effective Anion
      Receptors.
AB  - Derivatives of dehydroacetic acid comprising amide or urea subunits have been
      synthesized and their anion-binding properties investigated. Among a series of
      halides and oxyanions, the studied compounds selectively bind acetate and
      dihydrogen phosphate in acetonitrile and dimethyl sulfoxide. The corresponding
      complexation processes were characterized by means of 1 H NMR titrations, which
      revealed a 1:1 complex stoichiometry in most cases, with the exception of
      dihydrogen phosphate, which formed 2:1 (anion/ligand) complexes in acetonitrile.
      The complex stability constants were determined and are discussed with respect to
      the structural properties of the receptors, the hydrogen-bond-forming potential
      of the anions, and the characteristics of the solvents used. Based on the
      spectroscopic data and results of Monte Carlo simulations, the amide or urea
      groups were affirmed as the primary binding sites in all cases. The results of
      the computational methods indicate that an array of both inter- and
      intramolecular hydrogen bonds can form in the studied systems, and these were
      shown to play an important role in defining the overall stability of the
      complexes. Solubility measurements were carried out in both solvents and the
      thermodynamics of transfer from acetonitrile to dimethyl sulfoxide were
      characterized on a quantitative level. This has afforded a detailed insight into
      the impact of the medium on the complexation reactions.

PMID- 28493493
TI  - Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and mean platelet volume
      in Japanese patients with psoriasis and psoriatic arthritis: Response to therapy
      with biologics.
AB  - Recent studies indicate the presence of systemic inflammation in psoriatic
      patients, and this inflammatory status is significantly associated with a range
      of comorbidities. The aim of this study was to evaluate the clinical significance
      of novel inflammatory biomarkers, neutrophil-lymphocyte ratio (NLR), platelet
      lymphocyte ratio (PLR) and mean platelet volume (MPV) in Japanese patients with
      plaque-type psoriasis (PsV) and psoriatic arthritis (PsA). One hundred and eighty
      six patients with PsV and 50 patients with PsA treated with biologics, including
      infliximab, adalimumab and ustekinumab, were retrospectively analyzed before and
      after treatment. At baseline, NLR and PLR, as well as C-reactive protein (CRP),
      were significantly higher in PsA patients than those in PsV patients, and a
      significant correlation was found between NLR and PLR. In PsV patients, the NLR
      high and PLR-high subgroups exhibited significantly higher Psoriasis Area and
      Severity Index scores compared with the NLR-low and PLR-low subgroups,
      respectively, and the NLR-high subgroup also showed higher CRP levels. MPV value
      was negatively associated with the presence of arthritis, but its association
      with inflammation was less clear than that of NLR or PLR. After treatment of the
      patients with biologics for up to 12 months, NLR and PLR decreased promptly in
      parallel with a decrease of CRP, irrespective of the type of biologics used.
      Altogether, these results indicate that both NLR and PLR may be useful markers to
      evaluate systemic inflammation in psoriatic patients. They may serve as simple,
      convenient and cost-effective biomarkers to monitor the disease course after
      systemic therapy.

PMID- 28493494
TI  - STAT3 promotes bone fracture healing by enhancing the FOXP3 expression and the
      suppressive function of regulatory T cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a key signaling
      protein in the skeletal system as well as in the immune system. Accumulating
      evidence demonstrates that the inflammatory response is deeply involved in the
      healing process of bone fractures, but how the immune system is regulated during
      this process is unclear. In this study, we examined STAT3-mediated regulation of
      immunity in adult patients with closed tibia fracture. In all patients, the
      expression and activation of STAT3 peaked at around day 7 to day 14 after
      surgery, and gradually decreased during the rest of the healing period. At day 7
      (peak STAT3 expression and phosphorylation), the CD4+ CD25+ T cells from bone
      fracture patients presented the highest level of STAT3 activation among
      lymphocyte subsets. Therefore, we investigated the role of STAT3 in CD4+ CD25+ T
      cells. The level of FOXP3 expression by CD4+ CD25+ T cells was directly
      correlated with the level of STAT3 phosphorylation in these cells. The level of
      STAT3 phosphorylation in CD4+ CD25+ T cells was also inversely correlated with
      the level of IFN-gamma and TNF-alpha secretion in peripheral blood mononuclear
      cells. Inhibition of STAT3 significantly suppressed FOXP3 and IL-10 expression by
      CD4+ CD25+ T cells, as well as the ability of CD4+ CD25+ T cells to suppress T
      cell IFN-gamma and TNF-alpha secretion. Furthermore, early healers patients
      presented significantly higher STAT3 expression and phosphorylation than late
      healers, possibly due to the higher IL-6 and IL-10 levels in the serum of early
      healing patients. Together, these data demonstrated that STAT3 was beneficial to
      bone fracture healing, possibly by enhancing Treg-mediated suppression of
      counteracting inflammations, and suggested that STAT3 could be used as a
      prognostic marker to identify otherwise undistinguishable patients at risk of
      developing delayed union or nonunion.

PMID- 28493495
TI  - Silver-Catalyzed Three-Component 1,1-Aminoacylation of Homopropargylamines: alpha
      Additions for Both Terminal Alkynes and Isocyanides.
AB  - The reaction of secondary homopropargylamines, isocyanides, and water in the
      presence of a catalytic amount of silver acetate and subsequent purification by
      chromatography on silica gel afforded substituted proline amides in good to
      excellent yields. Primary homopropargylamines underwent a cyclizative Ugi-Joullie
      three-component reaction with isocyanides and carboxylic acids to afford
      functionalized N-acyl proline amides. High diastereoselectivity was observed in
      the synthesis of 4-alkoxy and 4,5-disubstituted proline derivatives. This work
      represents the first examples of a three-component cyclizative 1,1-aminoacylation
      of terminal alkynes.

PMID- 28493496
TI  - A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the
      Catalytic Site.
AB  - The design and synthesis of a glucose-based acridone derivative (GLAC), a potent
      inhibitor of glycogen phosphorylase (GP) are described. GLAC is the first
      inhibitor of glycogen phosphorylase, the electronic absorption properties of
      which are clearly distinguishable from those of the enzyme. This allows probing
      subtle interactions in the catalytic site. The GLAC absorption spectra,
      associated with X-ray crystallography and quantum chemistry calculations, reveal
      that part of the catalytic site of GP behaves as a highly basic environment in
      which GLAC exists as a bis-anion. This is explained by water-bridged hydrogen
      bonding interactions with specific catalytic site residues.

PMID- 28493497
TI  - Coordination Behavior of [Cp''2 Zr(eta1:1 -P4 )] towards Different Lewis Acids.
AB  - A detailed method for the preparation of [Cp''2 Zr(eta1:1 -P4 )] (1) is
      presented. The coordination behavior of 1 towards Lewis acidic transition metal
      complexes of tungsten, manganese, and iron, respectively, and main group
      compounds (AlMe3 , AlEt3 ) was investigated in detail by computational and
      experimental studies. In doing so, a series of unprecedented complexes with
      different coordination modes and multiple coordination numbers of the
      tetraphosphabicyclo[1.1.0]butane framework were synthesized. All products, as
      well as the starting materials, were comprehensively characterized by NMR
      spectroscopy, mass spectrometry, elemental analysis, and single crystal X-ray
      structural analysis.

PMID- 28493498
TI  - Endoscopic ultrasound-guided retrieval of a toothpick embedded in the stomach
      wall.
AB  - Patients with the complaint of ingested foreign body commonly present in the
      emergency department. Radiographic imaging is always done for the purpose of
      localization. However, radiolucent materials like wood are not easily picked up
      on CT scan. We report the case of a 33-year-old male patient who presented with
      the complaint of progressive abdominal pain and history of ingestion of a
      toothpick. It was removed by endoscopic ultrasound-guided localization-assisted
      targeted endoscopic dissection. Endoscopic ultrasound-guided localization reduced
      the length and depth of the required incision and helped to minimize the risk of
      damage to the surrounding tissue. (c) 2017 Wiley Periodicals, Inc. J Clin
      Ultrasound 45:603-604, 2017.

PMID- 28493499
TI  - Length-mass allometries in amphibians.
AB  - Body mass is rarely recorded in amphibians, and other body measurements (e.g.
      snout to vent length, SVL) are generally collected instead. However, length
      measurements, when used as proxies of body mass in comparative analyses, are
      problematic if different taxa and morphotypes are included. We developed
      allometric relationships to derive body mass from SVL measurements. We fitted
      phylogenetic generalized least square models for frogs (Anura) and salamanders
      (Caudata) and for several families separately. We tested whether allometric
      relationships differed between species with different habitat preferences and
      between morphs in salamanders. Models were fitted with SVL-mass measurements for
      88 frog and 42 salamander species. We assessed the predictive performance of the
      models by cross-validation. Overall, the models showed high explained variance
      and low forecasting errors. Models differed among semi-aquatic, terrestrial and
      arboreal frogs, and between paedomorphic and non-paedomorphic salamanders. Body
      mass estimates derived from our models allow for comparability of studies on
      multiple taxa and can be used for testing theories built upon evolutionary and
      ecological processes which are directly related to body mass.

PMID- 28493500
TI  - Conformational Analysis of the Mannosidase Inhibitor Kifunensine: A Quantum
      Mechanical and Structural Approach.
AB  - The varied yet family-specific conformational pathways used by individual
      glycoside hydrolases (GHs) offer a tantalising prospect for the design of tightly
      binding and specific enzyme inhibitors. A cardinal example of a GH-family
      specific inhibitor, and one that finds widespread practical use, is the natural
      product kifunensine, which is a low-nanomolar inhibitor that is selective for GH
      family 47 inverting alpha-mannosidases. Here we show, through quantum-mechanical
      approaches, that kifunensine is restrained to a "ring-flipped" 1 C4 conformation
      with another accessible, but higher-energy, region around the 1,4 B conformation.
      The conformations of kifunensine in complex with a range of GH47 enzymes
      including an atomic-level resolution (1 A) structure of kifunensine with
      Caulobacter sp. CkGH47 reported herein and with GH family 38 and 92 alpha
      mannosidases-were mapped onto the kifunensine free-energy landscape. These
      studies revealed that kifunensine has the ability to mimic the product state of
      GH47 enzymes but cannot mimic any conformational states relevant to the reaction
      coordinate of mannosidases from other families.

PMID- 28493501
TI  - Enzyme-Inspired Chiral Secondary-Phosphine-Oxide Ligand with Dual Noncovalent
      Interactions for Asymmetric Hydrogenation.
AB  - Inspired by the unique character of enzymes, we developed novel chiral SPO
      (secondary-phosphine-oxide) ligand (SPO-Wudaphos) which can enter into both ion
      pair and H-bond noncovalent interactions. The novel chiral SPO-Wudaphos exhibited
      excellent results in the asymmetric hydrogenation of alpha-methylene-gamma-keto
      carboxylic acids, affording the chiral gamma-keto acids with up to over 99 % ee.
      A series of control experiments and DFT calculations were conducted to illustrate
      the critical roles of both the ion pair and H-bond noncovalent interactions.

PMID- 28493502
TI  - Fasiglifam for glycaemic control in people with type 2 diabetes: A phase III,
      placebo-controlled study.
AB  - AIM: To investigate the effect of fasiglifam on glycaemic control in people with
      type 2 diabetes mellitus (T2DM). METHODS: In total, 421 people with T2DM and
      glycated haemoglobin (HbA1c) >=7.0% and <=10.5% who had received only diet and
      exercise treatment for >=12 weeks prior to screening were randomized to receive
      fasiglifam 25 or 50 mg or placebo. The primary efficacy endpoint was change from
      baseline in HbA1c at week 24. RESULTS: The mean participant age was 53.5 years,
      mean baseline body mass index 32.3 kg/m2 , and mean baseline HbA1c level 8.05%.
      Least squares mean changes in HbA1c from baseline to week 24 were: -0.93%
      (fasiglifam 50 mg), -0.65% (fasiglifam 25 mg) and -0.17% (placebo). Treatment
      emergent adverse events (TEAEs) occurred in 53.3%, 48.2% and 39.9% of
      participants receiving fasiglifam 25 mg, fasiglifam 50 mg, and placebo,
      respectively. Three participants in each group experienced a serious adverse
      event (AE). Nine participants had alanine aminotransferase (ALT) elevations >3*
      upper limit of normal: 5 (3.6%) in the fasiglifam 25-mg group, 4 (2.8%) in the
      fasiglifam 50-mg group, and none in the placebo group. CONCLUSIONS: The data
      indicate that fasiglifam effectively reduced HbA1c from baseline for 24 weeks in
      participants with T2DM. The incidence of TEAEs was higher in the fasiglifam
      groups; however, the incidence of serious AEs was low overall and similar between
      groups. ALT elevations were observed only in the fasiglifam groups, which
      contributed to the decision to terminate the fasiglifam programme after
      completion of the present study.

PMID- 28493503
TI  - Liver of the fish Gymnotus inaequilabiatus and nematode larvae infection:
      Histochemical features and expression of proliferative cell nuclear antigen.
AB  - Histopathological lesions due to third-larval stage of nematode Brevimulticaecum
      sp. within the liver of a subpopulation of 31 Gymnotus inaequilabiatus from the
      Pantanal Region (Brazil) were studied with histochemical and immunohistochemical
      methods. In 93.5% of fish, livers harboured nematode larvae and the intensity of
      infection ranged from 8 to 293. In livers with highest number of larvae, the
      hepatic tissue was occupied primarily by the nematodes. Each larva was encircled
      by focal inflammatory granulomatous reaction. Within the thickness of the
      granuloma, three concentric layers were recognized: an inner layer of densely
      packed epithelioid cells, a middle layer of mast cells (MCs) entrapped in a thin
      fibroblast-connective mesh and an outer layer of fibrous connective tissue with
      fibroblasts. Epithelioid cells and fibroblasts within the thickness of the
      granuloma wall were positive for proliferative cell nuclear antigen (PCNA).
      Moreover, several hepatocytes in infected liver were immunoreactive to PCNA.
      Occurrence of rodlet cells and MCs in parenchyma, in close proximity to the
      encysted nematode larvae and near the blood vessel of infected liver, was
      observed. Macrophage aggregates (MAs) were numerous within the granulomas and
      scattered in parenchyma of the infected liver. High quantity of haemosiderin was
      encountered in MAs and hepatocytes of infected liver.

PMID- 28493504
TI  - Imaging sonographic findings of in a case of proliferating trichilemmal tumor of
      a finger: A case report.
AB  - Proliferating trichilemmal tumor (PTT) is a rare tumor that originates from the
      outer root sheath of a hair follicle. About 90% of PTTs occur on the scalp. The
      sonographic findings of PTT in the subungual region have not been reported
      previously. In our case, sonography showed a heterogeneous mass containing
      echogenic foci with no detectable intratumoral vascularity. These echogenic foci
      probably represent keratin and cholesterol. (c) 2017 Wiley Periodicals, Inc. J
      Clin Ultrasound 46:215-217, 2018.

PMID- 28493505
TI  - Resilience in ecotoxicology: Toward a multiple equilibrium concept.
AB  - The term resilience describes stress-response patterns across scientific
      disciplines. In ecology, advances have been made to clearly define resilience
      based on underlying mechanistic assumptions. Engineering resilience (rebound) is
      used to describe the ability of organisms to recover from adverse conditions
      (disturbances), which is termed the rate of recovery. By contrast, the ecological
      resilience definition considers a systemic change, that is, when ecosystems
      reorganize into a new regime following disturbance. Under this new regime,
      structural and functional aspects change considerably relative to the previous
      regime, without recovery. In this context, resilience is an emergent property of
      complex systems. In the present study, we argue that both definitions and uses
      are appropriate in ecotoxicology, and although the differences are subtle, the
      implications and uses are profoundly different. We discuss resilience concepts in
      ecotoxicology, where the prevailing view of resilience is engineering resilience
      from chemical stress. Ecological resilience may also be useful for describing
      systemic ecological changes because of chemical stress. We present quantitative
      methods that allow ecotoxicologists and risk managers to assess whether an
      ecosystem faces an impending regime shift or whether it has already undergone
      such a shift. We contend that engineering and ecological resilience help to
      distinguish ecotoxicological responses to chemical stressors mechanistically and
      thus have implications for theory, policy, and application. Environ Toxicol Chem
      2017;36:2574-2580. (c) 2017 SETAC.

PMID- 28493506
TI  - Alemtuzumab dose adjusted for body weight is associated with earlier lymphocyte
      repletion and less infective episodes in the first year post renal
      transplantation - a retrospective study.
AB  - The optimal dose of alemtuzumab for renal transplant induction is not known, and
      the doses reported in the literature vary. This study compares two separate
      dosing regimens of alemtuzumab in renal transplantation. The first is a standard
      fixed dose of 30 mg (SD), and the second is a dose adjusted for body weight at
      0.4 mg/kg (AD). In this first year post-transplant, there was no difference in
      patient [HR 0.64 (0.22-1.86), P = 0.39] or allograft survival [HR 1.18 (0.48
      2.90), P = 0.72] between the two groups. There was also no difference in overall
      rejection-free survival [HR 1.12 (0.79-1.58), P = 0.53]. However, absolute
      lymphocyte count was significantly higher at all measured time points in the
      first year in the AD group. There were also less episodes of urosepsis [HR 1.38
      (1.03-1.85), P = 0.037] and fungal infection [HR 5.15 (2.00-13.28), P = 0.015] in
      the AD group compared with the SD group. This study shows that AD alemtuzumab is
      associated with earlier lymphocyte repletion and less infective episodes in the
      first year postrenal transplant, without increasing the risk of rejection. This
      work highlights the need for studies into the optimal dosing of monoclonal
      antibodies used in transplantation.

PMID- 28493507
TI  - PKC, ERK/p38 MAP kinases and NF-kappaB targeted signalling play a role in the
      expression and release of IL-1beta and CXCL8 in Porphyromonas gingivalis-infected
      THP1 cells.
AB  - Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining
      importance in cardiovascular pathogenesis. Protease-activated receptors (PARs),
      toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on
      monocytes recognize the structural components on P. gingivalis, inducing
      inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs,
      NODs, and the role of MAPK and NF-kappaB in IL-1beta and CXCL8 release. THP1
      cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain
      mutants: Rgp mutant E8 and Kgp mutant K1A. We observed modulation of PARs, TLRs,
      NOD, IL-1beta and CXCL8 expression by P. gingivalis. Gingipains hydrolyse IL
      1beta and CXCL8, which is more evident for IL-1beta accumulation at 24 h.
      Inhibition of PKC (protein kinase C), p38 and ERK (extracellular signal-regulated
      kinases) partially reduced P. gingivalis-induced IL-1beta at 6 h, whereas PKC and
      ERK reduced CXCL8 at both 6 and 24 h. Following NF-kappaB inhibition, P.
      gingivalis-induced IL-1beta and CXCL8 were completely suppressed to basal levels.
      Overall, TLRs, PARs and NOD possibly act in synergy with PKC, MAPK ERK/p38 and NF
      kappaB in P. gingivalis-induced IL-1beta and CXCL8 release from THP1 cells. These
      pro-inflammatory cytokines could affect leucocytes in circulation and exacerbate
      other vascular inflammatory conditions such as atherosclerosis.

PMID- 28493508
TI  - Apgar Score Components at 5 Minutes: Risks and Prediction of Neonatal Mortality.
AB  - BACKGROUND: The Apgar score consists of five components: heart rate, respiratory
      effort, muscle tone, reflex irritability, and colour. Although the Apgar score
      has been used for 60 years, the specific contribution of the Apgar score
      components with respect to risks and prediction of neonatal mortality remains
      unknown. Likewise, the value of reduced scores (including less than five Apgar
      score components) has rarely been investigated. METHODS: In a population-based
      cohort study of 148 765 liveborn singleton infants in Sweden 2008-2013, we
      investigated components of Apgar score at 5 min with respect to relative risks
      and prediction (using ROC curves, sensitivity, and positive predictive values) of
      neonatal mortality. RESULTS: Reduced values (0-1) of heart rate, respiratory
      effort, and colour were independently associated with increased relative risks of
      neonatal mortality. For the full Apgar score, the sensitivity and positive
      predictive values of neonatal mortality (cut-off <=3) were by gestational age:
      <=31 weeks: 56.1% and 49.2%; 32-36 weeks: 25.0% and 18.2%; and >=37 weeks: 35.2%
      and 9.3%, respectively. When only heart rate and respiratory effort were
      considered (range 0-4; cut-off <=2), corresponding values were 66.7% and 34.9%;
      37.5% and 13.0%; and 46.3% and 7.6%, respectively. CONCLUSIONS: A reduced Apgar
      score has generally the same predictability of neonatal mortality as the full
      Apgar score. The full Apgar score or reduced scores may be better predictors of
      neonatal mortality in very preterm infants (<=31 weeks) than in infants with
      longer gestations.

PMID- 28493509
TI  - Linking public health nursing competencies and service-learning in a global
      setting.
AB  - BACKGROUND: Nurse educators in baccalaureate programs are charged with addressing
      student competence in public health nursing practice. These educators are also
      responsible for creating nursing student opportunities for civic engagement and
      development of critical thinking skills. The IOM report (2010) on the Future of
      Nursing emphasizes the nurse educator's role in promoting collaborative
      partnerships that incorporate interdisciplinary and intraprofessional efforts to
      promote health. AIM: The purpose of this article is to describe an innovative
      approach to address public health nursing competencies and to improve the health
      and well-being of indigenous populations in a global setting through promotion of
      collaboration and service- learning principles. METHODS: As part of a hybrid
      elective course, baccalaureate nursing students from various nursing tracks
      participated in a 2 week immersion experience in Belize that included
      preimmersion preparation. These students were to collaborate among themselves and
      with Belizean communities to address identified health knowledge deficits and
      health-related needs for school-aged children and adult populations. RESULTS:
      Students successfully collaborated in order to meet health-related needs and to
      engage in health promotion activities in the Toledo district of Belize. They also
      gained practice in developing public health nursing competencies for entry-level
      nursing practice. Implementation of service-learning principles provided students
      with opportunities for civic engagement and self-reflection. DISCUSSION: Some
      challenges existed from the students', faculty, and global community's
      perspectives. Lack of culturally appropriate and country specific health
      education materials was difficult for students and the community. Faculty
      encountered challenges in communicating and collaborating with the Belizean
      partners. CONCLUSION: Commonalities exist between entry-level public health
      nursing competencies and service-learning principles. Using service-learning
      principles in the development of public health experiences increases the
      likelihood of success in achieving these competencies. While students
      demonstrated intraprofessional collaboration in a global setting, these same
      collaborative opportunities can occur in local communities.

PMID- 28493510
TI  - Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with
      sugammadex of high-dose rocuronium for a short procedure.
AB  - Some short procedures require deep neuromuscular blockade, which needs to be
      reversed at the end of the procedure. Forty-four patients undergoing elective
      laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45
      mg.kg-1 with neostigmine (50 MUg.kg-1 with glycopyrrolate 10 MUg.kg-1 ) reversal
      (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 )
      reversal (deep block group). The primary outcome was the intubating conditions
      during laryngoscopy secondary outcomes included recovery of neuromuscular block;
      conditions for tracheal intubation; satisfaction score as determined by the
      surgeon; onset of neuromuscular block; and postoperative sore throat. The onset
      of neuromuscular block was more rapid, and intubation conditions and ease of
      intra-operative laryngoscopy were more favourable, and the satisfaction score was
      lower in the moderate block group compared with the deep block group. No
      difference was found in the incidence of postoperative sore throat. In laryngeal
      micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was
      associated with better surgical conditions and a shorter recovery time than
      rocuronium 0.45 mg.kg-1 with neostigmine.

PMID- 28493512
TI  - Decreased expression of hsa_circ_0003570 in hepatocellular carcinoma and its
      clinical significance.
AB  - BACKGROUND: Circular RNAs (circRNAs) constitute a class of non-coding RNAs
      recently discovered to be widespread and abundant in mammalian cells. However,
      the expression features of most of circRNAs in hepatocellular carcinoma (HCC) are
      unraveled. In this study, we focused on hsa_circ_0003570, which was found to be
      down-regulated in HCC tissues in our previous microarray screening. METHODS: The
      hsa_circ_0003570 levels in HCC cell lines, HepG2, SMMC-7721, MHCC97L, MHCC97H,
      and HCCLM3, and human normal hepatic cell line L02 were detected by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR). Then, its levels in
      107 paired HCC tissues and adjacent non-tumor tissues, 60 liver biopsy samples
      from patients with chronic liver diseases were detected by qRT-PCR. The receiver
      operating characteristic curve (ROC) was used to evaluate the diagnostic value of
      hsa_circ_0003570 for HCC. RESULTS: Hsa_circ_0003570 was not only first found down
      regulated in HCC cell lines (P<.001) but also in HCC tissues (P<.001). Moreover,
      hsa_circ_0003570 was gradually decreased from chronic hepatitis (CH), to liver
      cirrhosis (LC) and to HCC tissues (P<.01). Its expression levels were
      significantly correlated with tumor diameter (P=.035), differentiation (P=.013),
      microvascular invasion (P=.045), Barcelona Clinic Liver Cancer stages (P=.011),
      tumor-node-metastasis stages (P=.016), and serum alpha-fetoprotein levels
      (P=.031). The ROC curve demonstrated that hsa_circ_0003570 had poor performance
      for differentiating HCC from LC and CH, but had relatively good performance for
      differentiating LC from CH. CONCLUSIONS: These results indicated that
      hsa_circ_0003570 expression levels were associated with HCC clinicopathological
      characteristics.

PMID- 28493511
TI  - Direct endovascular treatment: an alternative for bridging therapy in anterior
      circulation large-vessel occlusion stroke.
AB  - BACKGROUND AND PURPOSE: Whether intravenous thrombolysis prior to endovascular
      treatment in patients with anterior circulation large-vessel occlusion (LVO) is
      indispensable remains unclear. The aim was to retrospectively compare, in a
      Chinese population, the effectiveness and safety of direct endovascular treatment
      (DEVT) initiated within 4.5 h after onset with bridging therapy in acute anterior
      circulation LVO stroke patients. METHODS: A total of 363 patients, 160 in the
      bridging therapy group and 203 in the DEVT group, were enrolled between 2014 and
      2016. Using propensity score matching analysis, 276 patients were matched. A
      modified Rankin Scale score of 0-2 was considered as good functional outcome.
      RESULTS: Good functional outcome at 90 days in the DEVT group [40.6% (56/138)]
      did not significantly differ from that in the bridging group [44.9% (62/138)] (P
      = 0.53). Rates of symptomatic intracranial hemorrhage [13.8% (19/138) vs. 13.0%
      (18/138), P = 1.00] and mortality [25.4% (35/138) vs. 23.9% (33/138), P = 0.88]
      within 90 days were also not significantly different. Patients in the DEVT group
      had a lower rate of asymptomatic intracranial hemorrhage [28.3% (39/138) vs.
      44.9% (62/138), P = 0.01] and a higher rate of successful reperfusion [92.0%
      (127/138) vs. 81.9% (113/138), P = 0.02]. CONCLUSIONS: Our results suggest that,
      in Chinese patients with anterior circulation LVO stroke, direct endovascular
      mechanical thrombectomy initiated within an intravenous thrombolysis time window
      carries similar effectiveness to that of bridging therapy and a decreased
      asymptomatic intracranial hemorrhage risk. DEVT may be an alternative for
      bridging therapy. Future randomized controlled trials are warranted.

PMID- 28493513
TI  - Metal-Free Poly-Cycloaddition of Activated Azide and Alkynes toward
      Multifunctional Polytriazoles: Aggregation-Induced Emission, Explosive Detection,
      Fluorescent Patterning, and Light Refraction.
AB  - The metal-free click polymerization (MFCP) of activated alkynes and azides or
      activated azide and alkynes have been developed into powerful techniques for the
      construction of polytriazoles without the obsession of metallic catalyst residues
      problem. However, the MFCP of activated azides and alkynes is rarely applied in
      preparation of functional polytriazoles. In this paper, soluble multifunctional
      polytriazoles (PIa and PIb) with high weight-average molecular weights (Mw up to
      32 000) are prepared via the developed metal-free poly-cycloaddition of activated
      azide and alkynes in high yields (up to 90%). The resultant PIa and PIb are
      thermally stable, and show aggregation-induced emission characteristics, enabling
      their aggregates to detect explosives with superamplification effect. Moreover,
      thanks to their containing aromatic rings and polar moieties, PIa and PIb exhibit
      high refractive indices. In addition, they can also be cross-linked upon UV
      irradiation to generate 2D fluorescent patterning due to their remaining azide
      groups and containing ester groups. Thus, these multifunctional polytriazoles are
      potentially applicable in the optoelectronic and sensing fields.

PMID- 28493514
TI  - Protective effect and antibody response of DNA vaccine against salmonid
      alphavirus 3 (SAV3) in Atlantic salmon.
AB  - This work reports the effect of two DNA vaccines against salmonid alphavirus 3
      (SAV3) in Atlantic salmon. Presmolts were vaccinated by intramuscular injection
      of plasmids encoding the SAV3 structural polyprotein C-E3-E2-6K-E2 (pCSP), E2
      only (pE2), or plasmid without insert (pcDNA3.3). E2 is expressed at the surface
      of cells transfected with pCSP and internally in cells transfected with pE2. A
      commercial vaccine based on inactivated SAV (NCPD) was used for comparison. At 10
      weeks post-vaccination, only fish vaccinated with pCSP showed antibody against E2
      and virus-neutralizing activity. Vaccinated fish were infected with SAV3 to
      determine protection by virus quantitation in serum after 7 days and scoring of
      pathological changes after 21 days. Fish vaccinated with both pCSP and NCPD
      vaccines showed significant virus reduction in serum, while fish vaccinated with
      pE2 did not. All fish vaccinated with pcDNA3.3 and pE2 showed pathological
      changes in organs typical of PD, 60% of fish vaccinated with NCPD showed PD
      pathology, while fish vaccinated with pCSP did not show PD pathology. Taken
      together, DNA vaccination with pCSP provided strong protection for salmon against
      SAV3 infection, which in part may be due to production of virus-neutralizing
      antibodies.

PMID- 28493516
TI  - A Computational Study of a Single-Walled Carbon-Nanotube-Based Ultrafast High
      Capacity Aluminum Battery.
AB  - Exploring suitable electrode materials is a fundamental step toward developing Al
      batteries with enhanced performance. In this work, we explore using density
      functional theory calculations the feasibility of single-walled carbon nanotubes
      (SWNTs) as a cathode material for Al batteries. Carbon nanotubes with hollow
      structures and large surface area are able to overcome the difficulty of
      activating the opening of interlayer spaces as observed in graphite electrode
      during the first intercalation cycle. Our results show that AlCl4 binds strongly
      with the SWNT to result in an energetically and thermally stable AlCl4 -adsorbed
      SWNT system. Diffusion calculations show that the SWNT system allows ultrafast
      diffusion of AlCl4 with a more favorable inner surface diffusion than outer
      surface diffusion. Our charge-density difference and Bader atomic charge analysis
      confirm the oxidation of SWNT upon adsorption of AlCl4 , which shows a similar
      behavior to the previously studied graphite cathode. The average open-circuit
      voltage and AlCl4 storage capacity increases with increasing SWNT diameter and
      can be as high as 1.96 V and 275 mA h g-1 in (25,25) SWNT relative to graphite
      (70 mA h g-1 ). All of these properties show that SWNTs are a potential cathode
      material for high-performance Al batteries and should be explored further.

PMID- 28493515
TI  - Review of methods for measuring beta-cell function: Design considerations from
      the Restoring Insulin Secretion (RISE) Consortium.
AB  - The Restoring Insulin Secretion (RISE) study was initiated to evaluate
      interventions to slow or reverse the progression of beta-cell failure in type 2
      diabetes (T2D). To design the RISE study, we undertook an evaluation of methods
      for measurement of beta-cell function and changes in beta-cell function in
      response to interventions. In the present paper, we review approaches for
      measurement of beta-cell function, focusing on methodologic and feasibility
      considerations. Methodologic considerations included: (1) the utility of each
      technique for evaluating key aspects of beta-cell function (first- and second
      phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin
      effects) and (2) tactics for incorporating a measurement of insulin sensitivity
      in order to adjust insulin secretion measures for insulin sensitivity
      appropriately. Of particular concern were the capacity to measure beta-cell
      function accurately in those with poor function, as is seen in established T2D,
      and the capacity of each method for demonstrating treatment-induced changes in
      beta-cell function. Feasibility considerations included: staff burden, including
      time and required methodological expertise; participant burden, including time
      and number of study visits; and ease of standardizing methods across a
      multicentre consortium. After this evaluation, we selected a 2-day measurement
      procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage
      hyperglycaemic clamp procedure, augmented with arginine.

PMID- 28493517
TI  - Clinicopathological analysis of primary splenic diffuse large B-cell lymphoma.
AB  - Splenic infiltration is often seen in diffuse large B-cell lymphoma (DLBCL).
      However, primary splenic DLBCL is rare and studies on its clinicopathological
      features are limited. We assessed 66 cases of primary splenic DLBCL and 309
      control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B
      symptoms, poor performance status and CD5 positivity differed significantly
      between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL
      cases were classified histopathologically into two groups [white pulp pattern (n
      = 46), red pulp pattern (n = 20)]. Survival analysis showed no difference in
      overall survival between the primary splenic DLBCL and the control group, but the
      former had a more favourable progression-free survival. In the examination of
      primary splenic DLBCL, the white pulp pattern was statistically associated with a
      lower performance status (2-4), and a lower CD5 positivity than the red pulp
      pattern. In the survival analysis, the red pulp pattern demonstrated poorer
      overall survival. Multivariate analysis of overall survival in primary splenic
      DLBCL cases identified CD5 positivity as an indicator of poor prognosis.
      Classifying primary splenic DLBCL into white and red pulp patterns was useful in
      terms of clinicopathological features and overall survival.

PMID- 28493518
TI  - On the relationships between DSM-5 dysfunctional personality traits and social
      cognition deficits: A study in a sample of consecutively admitted Italian
      psychotherapy patients.
AB  - This study aims at testing the hypothesis that the Diagnostic and Statistical
      Manual of Mental Disorders fifth edition (DSM-5) alternative model of personality
      disorder (AMPD) traits may be significantly associated with deficits on 2
      different social cognition tasks, namely, the Reading the Mind in the Eyes Test
      and the Movie for the Assessment of Social Cognition, in a sample of
      consecutively admitted inpatients and outpatients. The sample was composed of 181
      consecutively admitted participants (57.5% women; mean age = 38.58 years).
      Correlation coefficients and partial correlation coefficients were computed in
      order to assess the associations among social cognition tasks, DSM-5 AMPD traits,
      and dimensionally assessed DSM-5 Section II personality disorders. Specific
      maladaptive traits listed in the DSM-5 AMPD were significantly associated with
      Reading the Mind in the Eyes Test scores and Movie for the Assessment of Social
      Cognition scores, even when the effect of selected DSM-5 Section II personality
      disorders was controlled for. Our results support the relevance of studying
      social cognitive functioning in subjects suffering from personality disorders.

PMID- 28493519
TI  - Neurotransmitters behind pain relief with transcranial magnetic stimulation -
      positron emission tomography evidence for release of endogenous opioids.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex
      has been shown to alleviate neuropathic pain. OBJECTIVES: To investigate the
      possible neurobiological correlates of cortical neurostimulation for the pain
      relief. METHODS: We studied the effects of M1/S1 rTMS on nociception, brain
      dopamine D2 and MU-opioid receptors using a randomized, sham-controlled, double
      blinded crossover study design and 3D-positron emission tomography (PET). Ten
      healthy subjects underwent active and sham rTMS treatments to the right M1/S1
      cortex with E-field navigated device. Dopamine D2 and MU-receptor availabilities
      were assessed with PET radiotracers [11 C]raclopride and [11 C]carfentanil after
      each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat
      evoked potential (CHEP) and blink reflex (BR) recordings were performed between
      the PET scans. RESULTS: MU-Opioid receptor availability was lower after active
      than sham rTMS (P <= 0.0001) suggested release of endogenous opioids in the right
      ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate
      cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal
      cortex and precentral gyrus. There were no differences in striatal dopamine D2
      receptor availability between active and sham rTMS, consistent with lack of long
      lasting measurable dopamine release. Active rTMS potentiated the dopamine
      regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP
      remained unchanged after active rTMS. CONCLUSIONS: rTMS given to M1/S1 activates
      the endogenous opioid system in a wide brain network associated with processing
      of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated
      inhibition may partly explain the clinical analgesic effects of rTMS.
      SIGNIFICANCE: Neurobiological correlates of rTMS for the pain relief are unclear.
      rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and
      heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated
      inhibition but not change the sensory discrimination of painful stimuli.

PMID- 28493520
TI  - HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less
      cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor
      immunity.
AB  - In East Asia and sub-Saharan Africa, chronic infection is the main cause of the
      development of hepatocellular carcinoma, an aggressive cancer with low survival
      rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy.
      Here, we investigated the possibility of using HBV-specific CD4+ cytotoxic T
      cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic
      CD4+ and CD8+ T cells were identified by HBV peptide pool stimulation. We found
      that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic
      CD4+ T cells and cytotoxic CD8+ T cells were present at similar numbers. But
      compared to the CD8+ cytotoxic T cells, the CD4+ cytotoxic T cells secreted less
      cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less
      effective at eliminating tumor cells. In addition, despite being able to secrete
      cytolytic factors, CD4+ T cells suppressed the cytotoxicity mediated by CD8+ T
      cells, even when CD4+ CD25+ regulator T cells were absent. Interestingly, we
      found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the
      cytotoxic CD4+ T cells. Neutralization of IL-10 abrogated the suppression of CD8+
      T cells by CD4+ CD25- T cells. Neither the frequency nor the absolute number of
      HBV-specific CD4+ cytotoxic T cells were correlated with the clinical outcome of
      advanced stage hepatocellular carcinoma patients. Together, this study
      demonstrated that in HBV-related hepatocellular carcinoma, CD4+ T cell-mediated
      cytotoxicity was present naturally in the host and had the potential to exert
      antitumor immunity, but its capacity was limited and was associated with
      immunoregulatory properties.

PMID- 28493521
TI  - A Freeze-Concentration and Polyampholyte-Modified Liposome-Based Antigen-Delivery
      System for Effective Immunotherapy.
AB  - Immunotherapy is an exciting new approach to cancer treatment. The development of
      a novel freeze-concentration method is described that could be applicable in
      immunotherapy. The method involves freezing cells in the presence of pH
      sensitive, polyampholyte-modified liposomes with encapsulated ovalbumin (OVA) as
      the antigen. In RAW 264.7 cells, compared to unfrozen, freeze-concentration of
      polyampholyte-modified liposomes encapsulating OVA resulted in efficient OVA
      uptake and also allowed its delivery to the cytosol. Efficient delivery of OVA to
      the cytosol was shown to be partly due to the pH-dependence of the polyampholyte
      modified liposomes. Cytosolic OVA delivery also resulted in significant up
      regulation of the major histocompatibility complex class I pathway through cross
      stimulation, as well as an increase in the release of IL-1beta, IL-6, and TNF
      alpha. The results demonstrate that the combination of a simple freeze
      concentration method and polyampholyte-modified liposomes might be useful in
      future immunotherapy applications.

PMID- 28493522
TI  - National survey on turnaround time of clinical biochemistry tests in 738
      laboratories in China.
AB  - BACKGROUND: This survey was initiated to estimate the current status of
      turnaround time (TAT) monitoring of clinical biochemistry in China, provide
      baseline data for establishment of quality specifications and analyze the impact
      factors of TAT. METHODS: 738 laboratories were included. Questionnaires involved
      general information and data of related indicators of TAT during 1 week were
      provided to participating laboratories. Nine quality indicators were covered,
      which were medians, 90th and outlier rates of pre-examination, examination, and
      post-examination TAT. The 25th percentile, median, and 75th percentile of TATs
      were calculated as optimum, desirable, and minimum quality specifications.
      Percentages and sigma values were used to describe the outlier rates. Mann
      Whitney and Kruskal-Wallis tests were used to identify the potential impacts of
      TAT. RESULTS: Response rate of this survey was 46.44%. More than 50% of the
      laboratories indicated they had set up target TATs in three time intervals and
      monitored TATs generally. The post-examination TAT of most laboratories was 0min,
      while the pre-examination and examination TAT varied. Sigma values of outlier
      rates for 45%~60% of laboratories were above 4, while 15%~20% of labs whose sigma
      values were below 3. Group comparisons suggested nurse or mechanical pipeline
      transportation, link laboratory information system with hospital information
      system, and using computer reporting instead of printing report were related to
      shorter TATs. CONCLUSIONS: Despite of the remarkable progresses of TATs in China,
      there was also room to improve. Laboratories should strengthen the construction
      of information systems, identify reasons for TAT delay to improve the service
      quality continuously.

PMID- 28493523
TI  - Fibrillar collagen genes are not coordinately upregulated with TGF beta1
      expression in finasteride-treated prostate.
AB  - Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary
      tract symptoms (LUTS) in older men. In this regard, recent studies have attempted
      to define the relationships between prostatic fibrosis, LUTS, and increased
      expression of transforming growth factor beta1 (TGF beta1) in BHP. Therapeutic
      approaches for BPH such as 5-alpha-reductase inhibitors and alpha-adrenergic
      blocking agents increase TGF beta1 expression in the prostatic tissue. Here, we
      investigated the effects of the 5-alpha-reductase inhibitor-finasteride-on rat
      ventral prostate tissue, especially with regard to the tissue distribution and
      gene expression of fibrillar collagens. Adult Wistar rats (n = 15) were treated
      with finasteride (25 mg/kg/day) by subcutaneous injection for 7 and 30 days. Age
      matched, vehicle-treated (n = 15) adult Wistar rats were used as control.
      Finasteride treatment reduced prostate size and increased the area of types I and
      III collagen fibers in the prostatic stroma. As expected, TGF beta1 mRNA
      expression was upregulated by finasteride treatment. However, COL1A1 and COL3A1
      mRNA expressions decreased after both 7 and 30 days of finasteride treatment,
      suggesting that finasteride treatment promotes prostate parenchyma and stroma
      changes, which lead to the observed types I and III collagen remodeling without
      de novo collagen synthesis. The upregulation of TGF beta1 mRNA and protein
      associated with the 5-alpha-reductase inhibitor is more closely related to
      epithelial and stromal cell death pathways than to prostatic fibrosis.

PMID- 28493524
TI  - Rapid identification and global characterization of multiple constituents from
      the essential oil of Cortex Dictamni based on GC-MS.
AB  - The root of Dictamnus dasycarpus Turcz., also known as Cortex Dictamni, is a
      Chinese herbal medicine that has been commonly used in the treatment of
      inflammation, microbial infection, cancer, and other diseases in China for
      thousands of years. Recently, the essential oil of Cortex Dictamni has been
      widely studied, and a large number of volatile constituents have been discovered.
      However, the research of the essential oil of Cortex Dictamni in vivo remains
      unknown, especially the constituents absorbed into blood after oral
      administration. Hence, a sensitive and rapid method using gas chromatography with
      mass spectrometry combined with MassHunter software and the National Institute of
      Standards and Technology 2014 database was used to investigate the absorbed
      components in rat serum after oral administration of the essential oil of Cortex
      Dictamni. With the established method, a total of 36 compounds were screened and
      identified in the essential oil of Cortex Dictamni based on the mass spectrometry
      data and compound database. Among them, eight compounds, elemol, thymol methyl
      ether, beta-eudesmol, beta-cyclocostunolid, guaiazulene, trans-4-hydroxystilbene,
      ethyl oleate, and monoelaidin, were tentatively characterized in rat serum. This
      work demonstrated that the established method proved to be a powerful technique
      for rapid, simple, reliable, and automated identification of bioactive components
      of herbal medicine.

PMID- 28493528
TI  - What the neighbors say.

PMID- 28493526
TI  - Real-time MRI guidance of cardiac interventions.
AB  - : Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac
      procedures because it is ionizing radiation-free and offers flexible soft-tissue
      contrast. Interventional cardiac MR promises to improve existing procedures and
      enable new ones for complex arrhythmias, as well as congenital and structural
      heart disease. Guiding invasive procedures demands faster image acquisition,
      reconstruction and analysis, as well as intuitive intraprocedural display of
      imaging data. Standard cardiac MR techniques such as 3D anatomical imaging,
      cardiac function and flow, parameter mapping, and late-gadolinium enhancement can
      be used to gather valuable clinical data at various procedural stages. Rapid
      intraprocedural image analysis can extract and highlight critical information
      about interventional targets and outcomes. In some cases, real-time interactive
      imaging is used to provide a continuous stream of images displayed to
      interventionalists for dynamic device navigation. Alternatively, devices are
      navigated relative to a roadmap of major cardiac structures generated through
      fast segmentation and registration. Interventional devices can be visualized and
      tracked throughout a procedure with specialized imaging methods. In a clinical
      setting, advanced imaging must be integrated with other clinical tools and
      patient data. In order to perform these complex procedures, interventional
      cardiac MR relies on customized equipment, such as interactive imaging
      environments, in-room image display, audio communication, hemodynamic monitoring
      and recording systems, and electroanatomical mapping and ablation systems.
      Operating in this sophisticated environment requires coordination and planning.
      This review provides an overview of the imaging technology used in MRI-guided
      cardiac interventions. Specifically, this review outlines clinical targets,
      standard image acquisition and analysis tools, and the integration of these tools
      into clinical workflow. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn.
      Reson. Imaging 2017;46:935-950.

PMID- 28493527
TI  - Characterization of a sandwich ELISA for the quantification of all human
      periostin isoforms.
AB  - BACKGROUND: Periostin (osteoblast-specific factor OSF-2) is a secreted protein
      occurring in seven known isoforms, and it is involved in a variety of biological
      processes in osteology, tissue repair, oncology, cardiovascular and respiratory
      systems or allergic manifestations. To analyze functional aspects of periostin,
      or the ability of periostin as potential biomarker in physiological and
      pathological conditions, there is the need for a precise, well-characterized
      assay that detects periostin in peripheral blood. METHODS: In this study the
      development of a sandwich ELISA using monoclonal and affinity-purified polyclonal
      anti-human periostin antibodies was described. Antibodies were characterized by
      mapping of linear epitopes with microarray technology, and by analyzing cross
      reactive binding to human periostin isoforms with western blot. The assay was
      validated according to ICH/EMEA guidelines. RESULTS: The monoclonal coating
      antibody binds to a linear epitope conserved between the isoforms. The polyclonal
      detection antibody recognizes multiple conserved linear epitopes. Therefore, the
      periostin ELISA detects all known human periostin isoforms. The assay is
      optimized for human serum and plasma and covers a calibration range between 125
      and 4000 pmol/L for isoform 1. Assay characteristics, such as precision (intra
      assay: <=3%, inter-assay: <=6%), spike-recovery (83%-106%), dilution linearity
      (95%-126%), as well as sample stability meet the standards of acceptance.
      Periostin levels of apparently healthy individuals are 864+/-269 pmol/L (serum)
      and 817+/-170 pmol/L (plasma) respectively. CONCLUSION: This ELISA is a reliable
      and accurate tool for determination of all currently known periostin isoforms in
      human healthy and diseased samples.

PMID- 28493529
TI  - Pain in knee osteoarthritis is associated with variation in the neurokinin
      1/substance P receptor (TACR1) gene.
AB  - BACKGROUND: Substance P (SP) is a pain- and inflammation-related neuropeptide
      which preferentially binds to the neurokinin receptor 1 (NK1 ). SP and NK1
      receptors have been implicated in joint pain, inflammation and damage in animal
      models and human studies of osteoarthritis (OA). The aim of this study was to
      test if genetic variation at the neurokinin 1 receptor gene (TACR1) is associated
      with pain in individuals with radiographic knee OA. METHODS: Participants from
      the Genetics of OA and Lifestyle study were used for the discovery group (n =
      1615). Genotype data for six SNPs selected to cover most variation in the TACR1
      gene were used to test for an association with symptomatic OA. Replication
      analysis was performed using data from the Chingford 1000 Women Study,
      Hertfordshire Cohort Study, Tasmanian Older Adult Cohort Study and the Clearwater
      OA Study. In total, n = 1715 symptomatic OA and n = 735 asymptomatic OA
      individuals were analysed. RESULTS: Out of six SNPs tested in the TACR1 gene, one
      (rs11688000) showed a nominally significant association with a decreased risk of
      symptomatic OA in the discovery cohort. This was then replicated in four
      additional cohorts. After adjusting for age, gender, body mass index and
      radiographic severity, the G (minor) allele at rs11688000 was associated with a
      decreased risk of symptomatic OA compared to asymptomatic OA cases (p = 9.90 * 10
      4 , OR = 0.79 95% 0.68-0.90 after meta-analysis). CONCLUSIONS: This study
      supports a contribution from the TACR1 gene in human OA pain, supporting further
      investigation of this gene's function in OA. SIGNIFICANCE: This study contributes
      to the knowledge of the genetics of painful osteoarthritis, a condition which
      affects millions of individuals worldwide. Specifically, a contribution from the
      TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.

PMID- 28493530
TI  - M2 macrophages induce EMT through the TGF-beta/Smad2 signaling pathway.
AB  - IPF is characterized by fibroblast accumulation, collagen deposition, and ECM
      remodeling, with myofibroblasts believed to be the effector cell type.
      Myofibroblasts develop due to EMT of lung alveolar epithelial cells, which can be
      induced by TGF-beta. M2 macrophages, a macrophage subpopulation, secrete large
      amounts of TGF-beta. To clarify the relationship between IPF, EMT, TGF-beta, and
      M2 macrophages, a bleomycin-induced pulmonary fibrosis mouse model was used.
      Seventeen days after mice were treated with bleomycin, the successful
      establishment of a pulmonary fibrosis model was confirmed by HE stain and
      Masson's trichrome stain. We found evidence in support of EMT, such as elevated
      protein levels of alpha-SMA in lung tissue and decreased levels of E-cadherin and
      CK-18. Additionally, increased TGF-beta levels and TGF-beta/Smad2 signaling
      activation was observed. Macrophages were recruited to pulmonary alveoli.
      Alveolar macrophages were phenotyped and identified as M2 macrophages, with up
      regulated CD206 on the cell surfaces. For in vitro studies, we treated RAW 264.7
      cells with IL-4 for 24 h, and the cells were then utilized as M2 macrophages. TGF
      beta levels increased significantly in the culture supernatant. Forty-eight hours
      after lung epithelial cells (MLE-12) were co-cultured with the M2 macrophages,
      the expression of alpha-SMA increased, and E-cadherin and CK-18 decreased. When a
      TGF-beta receptor inhibitor, LY2109761 was used, the EMT induced by M2
      macrophages was blocked. In conclusion, we demonstrated that M2 macrophages
      induce EMT through the TGF-beta/Smad2 signaling pathway.

PMID- 28493532
TI  - Metrics and the Scientific Literature: Deciding What to Read.

PMID- 28493533
TI  - Combination diagnosis of multi-slice spiral computed tomography and secretary
      phospholipase A2-IIa for solitary pulmonary nodules.
AB  - INTRODUCTION: This study was aimed to compare the diagnostic value of multi-slice
      spiral computed tomography (CT) and secretary phospholipase A2-IIa (sPLA2-IIa) in
      differentiating between malignant and benign solitary pulmonary nodules (SPNs).
      METHODS: A total of 223 patients with SPNs (91 patients with malignant SPNs and
      132 patients with benign SPNs) were included from Weihai Central Hospital during
      October 2014 to December 2016. SPN diagnosis was confirmed in all patients using
      needle biopsy, surgery and bronchoscopy. The patients were managed with dynamic
      multi-slice CT scans, and their sPLA2-IIa levels were also detected. By selecting
      the area of interest of focus, the perfusion parameters of multi-slice CT
      targeting the focus were obtained. RESULTS: The levels of MTT, PS, BV, BF and
      sPLA2-IIa significantly increased with increasing severity of SPNs (P<.05).
      Notably, BV (area under the ROC curve [AUC]=0.915; 95%CI: 0.88-0.95;
      sensitivity=91.21%; specificity=78.79%) showed a higher potential to discriminate
      patients with malignant SPNs from those with benign SPNs than did BF (AUC=0.712;
      95%CI: 0.65-0.78; sensitivity=72.50%; specificity=59.10%), PS (AUC=0.772; 95%CI:
      0.71-0.84; sensitivity=65.93%; specificity=82.58%) and MTT (AUC=0.600; 95%CI:
      0.52-0.68; sensitivity=52.75%; specificity=78.03%). Finally, the combined
      diagnostic value of BV and sPLA2-IIa was quite ideal (AUC=0.947; 95%CI: 0.92
      0.97; sensitivity=85.70%; specificity=92.70%) for malignant and benign SPNs.
      CONCLUSIONS: The combined diagnostic value of BV and sPLA2-IIa appeared as a
      desirable detection method for malignant and benign SPNs.

PMID- 28493531
TI  - Ternary complex of human RORgamma ligand-binding domain, inverse agonist and SMRT
      peptide shows a unique mechanism of corepressor recruitment.
AB  - Retinoid-related orphan receptor gamma (RORgamma) directly controls the
      differentiation of Th17 cell and the production of interleukin-17, which plays an
      integral role in autoimmune diseases. To obtain insight into RORgamma, we have
      determined the first crystal structure of a ternary complex containing RORgamma
      ligand-binding domain (LBD) bound with a novel synthetic inhibitor and a
      repressor peptide, 22-mer peptide from silencing mediator of retinoic acid and
      thyroid hormone receptor (SMRT). Comparison of a binary complex of nonliganded
      (apo) RORgamma-LBD with a nuclear receptor co-activator (NCoA-1) peptide has
      shown that our inhibitor displays a unique mechanism different from those caused
      by natural inhibitor, ursolic acid (UA). The compound unprecedentedly induces
      indirect disruption of a hydrogen bond between His479 on helix 11 (H11) and
      Tyr502 on H12, which is crucial for active conformation. This crystallographic
      study will allow us to develop novel synthetic compounds for autoimmune disease
      therapy.

PMID- 28493534
TI  - Determination of triazine herbicides in juice samples by microwave-assisted ionic
      liquid/ionic liquid dispersive liquid-liquid microextraction coupled with high
      performance liquid chromatography.
AB  - A novel microextraction method, termed microwave-assisted ionic liquid/ionic
      liquid dispersive liquid-liquid microextraction, has been developed for the rapid
      enrichment and analysis of triazine herbicides in fruit juice samples by high
      performance liquid chromatography. Instead of using hazardous organic solvents,
      two kinds of ionic liquids, a hydrophobic ionic liquid (1-hexyl-3
      methylimidazolium hexafluorophosphate) and a hydrophilic ionic liquid (1-butyl-3
      methylimidazolium tetrafluoroborate), were used as the extraction solvent and
      dispersion agent, respectively, in this method. The extraction procedure was
      induced by the formation of cloudy solution, which was composed of fine drops of
      1-hexyl-3-methylimidazolium hexafluorophosphate dispersed entirely into sample
      solution with the help of 1-butyl-3-methylimidazolium tetrafluoroborate. In
      addition, an ion-pairing agent (NH4 PF6 ) was introduced to improve recoveries of
      the ionic liquid phase. Several experimental parameters that might affect the
      extraction efficiency were investigated. Under the optimum experimental
      conditions, the linearity for determining the analytes was in the range of 5.00
      250.00 MUg/L, with the correlation coefficients of 0.9982-0.9997. The practical
      application of this effective and green method is demonstrated by the successful
      analysis of triazine herbicides in four juice samples, with satisfactory
      recoveries (76.7-105.7%) and relative standard deviations (lower than 6.6%). In
      general, this method is fast, effective, and robust to determine triazine
      herbicides in juice samples.

PMID- 28493535
TI  - The mongolian gerbil (Meriones unguiculatus) as a model for inflammation-promoted
      prostate carcinogenesis.
AB  - One of the recognized issues in prostate cancer research is the lack of animal
      models allowing the research of pathological, biochemical, and genetic factors in
      immunocompetent animals. Our research group has successfully employed the gerbil
      in several studies for prostate diseases. In the present work, we aimed to
      analyze the effect of chronic bacterial inflammation on N-methyl-N-nitrosourea
      (MNU)-induced prostate carcinogenesis in gerbils. Histopathological assessment of
      the prostatic complex revealed that treatment combinations with MNU plus
      testosterone or bacterial infection resulted in a promotion of prostate cancer,
      with bacterial inflammation being more effective in increasing premalignant and
      malignant tissular alterations than testosterone in the prostate. Furthermore,
      chronic bacterial inflammation itself induced premalignant lesions in the ventral
      lobe and increased their frequency in the dorsolateral lobe as well as malignant
      lesions in the ventral prostate. These animals showed a rich inflammatory
      microenvironment, characterized as intraluminal and periductal foci. These data
      indicate that chronic inflammation induced by Escherichia coli acts as a potent
      tumor promoter, in the early stages of carcinogenesis in the gerbil, in line with
      the hypothesis of inflammation supporting several steps of tumor development in
      the prostate gland.

PMID- 28493537
TI  - Exploring the expression bar code of SAA variants for gastric cancer detection.
AB  - We reported an integrated platform to explore serum protein variant pattern in
      cancer and its utility as a new class of biomarker panel for diagnosis. On the
      model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass
      spectrometry for enrichment, identification and quantitation of SAA variants from
      serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54
      controls, and 120 patients from other cancer. The result revealed surprisingly
      heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA
      variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N
      terminal-truncated forms, and three novel SAA oxidized isotypes, in which the
      variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic
      model was developed for dimension reduction and computational classification of
      the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 +/- 3.2E
      3) for differentiating gastric cancer group from gastritis and normal groups
      (sensitivity, 0.76; specificity, 0.81) and was validated with external validation
      cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light
      on the occurrence and modification extent of under-represented serum protein
      variants in cancer, but also suggested a new concept of diagnostic platform by
      serum protein variant profile.

PMID- 28493536
TI  - Functional hypergraph uncovers novel covariant structures over neurodevelopment.
AB  - Brain development during adolescence is marked by substantial changes in brain
      structure and function, leading to a stable network topology in adulthood.
      However, most prior work has examined the data through the lens of brain areas
      connected to one another in large-scale functional networks. Here, we apply a
      recently developed hypergraph approach that treats network connections (edges)
      rather than brain regions as the unit of interest, allowing us to describe
      functional network topology from a fundamentally different perspective.
      Capitalizing on a sample of 780 youth imaged as part of the Philadelphia
      Neurodevelopmental Cohort, this hypergraph representation of resting-state
      functional MRI data reveals three distinct classes of subnetworks (hyperedges):
      clusters, bridges, and stars, which respectively represent homogeneously
      connected, bipartite, and focal architectures. Cluster hyperedges show a strong
      resemblance to previously-described functional modules of the brain including
      somatomotor, visual, default mode, and salience systems. In contrast, star
      hyperedges represent highly localized subnetworks centered on a small set of
      regions, and are distributed across the entire cortex. Finally, bridge hyperedges
      link clusters and stars in a core-periphery organization. Notably, developmental
      changes within hyperedges are ordered in a similar core-periphery fashion, with
      the greatest developmental effects occurring in networked hyperedges within the
      functional core. Taken together, these results reveal a novel decomposition of
      the network organization of human brain, and further provide a new perspective on
      the role of local structures that emerge across neurodevelopment. Hum Brain Mapp
      38:3823-3835, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28493538
TI  - Fine-scale analysis of heavily invaded Italian freshwater fish assemblages.
AB  - Inland waters are highly vulnerable to the introduction and spread of non-native
      species, due to heavy human use of aquatic ecosystems and the natural linkages
      among streams and lakes. This is particularly noticeable in freshwater fish
      communities. To better evaluate how these communities are affected by non-native
      species introductions, we conducted a fine-scale analysis of the changes in
      Italian freshwater fish assemblages after species introduction. For this
      analysis, we collected information on fish species present in 44 basins. The
      present Italian freshwater fish fauna is composed of 48 native and 41 established
      introduced species, while a further 15 introduced species have been reported but
      are not yet considered naturalized. The changes in the fish assemblages mostly
      took place in the past 2 centuries and have increased recently, with nearly 60%
      of the species introduced in the past 3 decades. The number of species introduced
      per basin ranged from 0 to 35 (mean 10.85 +/- 7.77 species/basin), and in 10
      basins the number of species introduced is now equal to or even higher than the
      number of native species. In the past, introduced species mainly originated from
      America, but over the past three decades, an increase of introductions from other
      parts of Europe and Asia has been recorded. Our results show that basins already
      rich in native species tend to become even richer as a consequence of the
      establishment of introduced species. This confirms the trend toward a biotic
      homogenization of ecosystems even at a local scale, due to an increase in the
      human-mediated spread of generalist species.

PMID- 28493539
TI  - The influence of bacteria on multitrophic interactions among plants, psyllids,
      and pathogen.
AB  - The recent emergence of several plant diseases caused by psyllid-borne bacterial
      pathogens worldwide (Candidatus Liberibacter spp.) has created renewed interest
      on the interaction between psyllids and bacteria. In spite of these efforts to
      understand psyllid association with bacteria, many aspects of their interactions
      remain poorly understood. As more organisms are studied, subtleties on the
      molecular interactions as well as on the effects of the bacteria on the psyllid
      host are being uncovered. Additionally, psyllid-borne bacterial phytopathogens
      can also affect the host plant, which in turn can impact psyllid physiology and
      behavior. Here, we review the current literature on different aspects of the
      influence of bacteria on multitrophic interactions among plants, psyllids, and
      pathogens. We then highlight gaps that need to be addressed to advance this
      field, which can have significant implications for controlling these newly
      emergent and other plant diseases.

PMID- 28493540
TI  - Corrigendum: A GAL4-inducible transgenic tool kit for the in vivo modulation of
      Rho GTPase activity in zebrafish.

PMID- 28493541
TI  - Sudden gains in exposure-focused cognitive-behavioral group therapy for panic
      disorder.
AB  - : In the context of psychological treatment, a sudden gain is a large and
      enduring improvement in symptom severity that occurs between two single therapy
      sessions. The influence of sudden gains on long-term outcomes and functional
      impairment in anxiety disorders is not well understood, and little is known with
      regard to panic disorder in particular. In addition, previous research on
      patients with anxiety disorders has produced inconsistent results regarding the
      relationship between sudden gains and cognitive change. We examined the incidence
      of sudden gains in a large sample (n = 116) of panic disorder patients undergoing
      exposure-focused cognitive-behavioral group therapy, and compared panic severity,
      functional impairment, and cognitive change in patients with and without sudden
      gains at posttreatment and 6-month follow-up. Participants who experienced sudden
      gains displayed lower levels of panic severity and functional impairment at
      posttreatment and 6-month follow-up than those who did not experience sudden
      gains. However, we observed no difference in cognitive changes between groups,
      either at posttreatment or at follow-up. Our results demonstrate that the
      beneficial effects of sudden gains on therapeutic outcomes not only extend to
      long-term and functional outcome measures but are also evident in less cognitive
      (i.e., exposure-focused) forms of psychological treatment. KEY PRACTITIONER
      MESSAGE: Sudden gains are common in panic disorder patients undergoing exposure
      based cognitive-behavioral group therapy. Sudden gains during exposure-focused
      therapy are linked to greater improvement in panic disorder severity and
      functional impairment. The positive impact of sudden gains on panic disorder
      severity and functional impairment is maintained in the long term.

PMID- 28493542
TI  - Dynamic changes of metabolite accumulation in Scrophulariae Radix based on liquid
      chromatography-tandem mass spectrometry combined with multivariate statistical
      analysis.
AB  - Scrophulariae Radix is one of the most popular traditional Chinese medicines. The
      harvesting time of Scrophulariae Radix is closely related to the quality of
      products in this traditional Chinese medicine. The goal of the study is to
      analyze the dynamic changes of metabolite accumulation in Scrophulariae Radix.
      The difference of constituents in Scrophulariae Radix harvested at different
      times was analyzed by liquid chromatography with triple quadrupole-time of flight
      tandem mass spectrometry coupled with principal component analysis and partial
      least-square discriminant analysis. According to the accurate mass of molecular
      and product ions provided by triple quadrupole-time of flight tandem mass
      spectrometry, a total of 30 differential constituents were identified.
      Furthermore, the contents of ten index differential constituents in Scrophulariae
      Radix were simultaneously determined by liquid chromatography coupled with triple
      quadrupole-linear ion trap tandem mass spectrometry. Gray relational analysis was
      performed to evaluate the samples harvested at different times according to the
      contents of ten constituents. All of the results demonstrated that the quality of
      Scrophulariae Radix collected at traditional harvest time was better. This study
      will provide the basic information for revealing the dynamic change law of
      metabolite accumulation of Scrophulariae Radix and exploring its quality forming
      mechanism.

PMID- 28493543
TI  - Contribution of patient, physician, and environmental factors to demographic and
      health variation in colonoscopy follow-up for abnormal colorectal cancer
      screening test results.
AB  - BACKGROUND: Patient, physician, and environmental factors were identified, and
      the authors examined the contribution of these factors to demographic and health
      variation in colonoscopy follow-up after a positive fecal occult blood test/fecal
      immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT
      positive patients were identified from 120 Veterans Health Administration (VHA)
      facilities between August 16, 2009 and March 20, 2011 and were followed for 6
      months. Patient demographic (race/ethnicity, sex, age, marital status) and health
      characteristics (comorbidities), physician characteristics (training level,
      whether primary care provider) and behaviors (inappropriate FOBT/FIT screening),
      and environmental factors (geographic access, facility type) were identified from
      VHA administrative records. Patient behaviors (refusal, private sector
      colonoscopy use) were estimated with statistical text mining conducted on clinic
      notes, and follow-up predictors and adjusted rates were estimated using
      hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a
      colonoscopy at a VHA facility within 6 months. Age and comorbidity score were
      negatively associated with follow-up. Blacks were more likely to receive follow
      up than whites. Environmental factors attenuated but did not fully account for
      these differences. Patient behaviors (refusal, private sector colonoscopy use)
      and physician behaviors (inappropriate screening) fully accounted for the small
      reverse race disparity and attenuated variation by age and comorbidity score.
      Patient behaviors (refusal and private sector colonoscopy use) contributed more
      to variation in follow-up rates than physician behaviors (inappropriate
      screening). CONCLUSIONS: In the VHA, blacks are more likely to receive
      colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up
      rates markedly decline with advancing age and comorbidity burden. Patient and
      physician behaviors explain race variation in follow-up rates and contribute to
      variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017.
      This article is a US Government work and is in the public domain in the USA.

PMID- 28493544
TI  - Recurrence patterns following irreversible electroporation for hepatic
      malignancies.
AB  - BACKGROUND: Irreversible electroporation (IRE) has emerged as a novel, safe
      ablative therapy for peri-vascular lesions. However, there remains a paucity of
      data on long-term outcomes. METHODS: We identified patients who underwent open
      IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local
      ablation-zone recurrence (LR) was determined by cross-sectional imaging.
      Cumulative incidence (CumI) of LR was calculated and a competing risks regression
      assessed factors associated with LR. RESULTS: Forty patients had 77 lesions
      treated. The majority of lesions were of colorectal origin (74%). Median tumor
      size was 1.3 cm (range 0.5-6). Most patients (86%) had prior systemic therapy and
      29% received systemic therapy following IRE. With a median follow-up of 25.7
      months (range 4.5-58.8 months), 10 lesions in 9 patients recurred locally (CumI:
      13.4%, 95%CI: 7.8-22.2%). Median estimated time to LR was not reached and no LR
      occurred after 19 months. Factors significantly associated with LR included
      ablation zone size (HR 1.58; 95%CI 1.12-2.23; P = 0.0093) and body mass index (HR
      1.21 95%CI 1.10-1.34; P = 0.0001). CONCLUSION: IRE LR rates were low after the
      treatment of well selected, small tumors. This technique is useful for lesions in
      anatomic locations precluding resection or thermal ablation.

PMID- 28493548
TI  - Time for a New Approach to Studying Older People with Ischemic Heart Disease.

PMID- 28493546
TI  - Palmar-plantar erythrodysesthesia syndrome following treatment with high-dose
      methotrexate or high-dose cytarabine.
AB  - BACKGROUND: Palmar-plantar erythrodysesthesia syndrome (PPES) is an uncommon side
      effect of high-dose cytarabine or methotrexate. Prior case reports of PPES have
      been limited, and the predisposing factors for the development of PPES remain
      unknown. METHODS: A review of databases identified 22 patients (1.3%) who
      developed 39 episodes of PPES among 1720 patients after treatment with high-dose
      cytarabine or methotrexate. RESULTS: Symptoms lasted a mean of 6.4 days. Hands
      and feet were both involved in 68% of the initial episodes. Parenteral opioids
      were required for pain control by 27% of the patients. In comparison with the
      1698 children treated with similar therapy, the children who developed PPES were
      older (mean age at diagnosis, 14.3 vs 7.7 years; P = 7.5 * 10-7 ). The frequency
      of PPES was less common in patients receiving methotrexate alone (7 of 946 or
      0.7%) versus cytarabine (7 of 205 or 3.4%; P = .005) but was not different for
      those receiving both high-dose methotrexate and cytarabine (8 of 569 or 1.4%; P =
      .32). Prolonged infusions of methotrexate were associated with less frequent PPES
      in comparison with rapid infusions (P = 1.5 * 10-5 ), as was the co
      administration of dexamethasone with cytarabine (P = 2.5 * 10-6 ). Self-described
      race and sex were not associated with PPES. In a multivariate analysis, older age
      and high-dose cytarabine administration without dexamethasone remained associated
      with PPES (P = 1.1 * 10-4 and P = .038, respectively). A genome-wide association
      study did not identify any associations with PPES meeting the genome-wide
      significance threshold, but top variants were enriched for skin expression
      quantitative trait loci, including rs11764092 in AUTS2 (P = 6.45 * 10-5 ).
      CONCLUSIONS: These data provide new insight into the incidence of PPES as well as
      its risk factors. Cancer 2017;123:3602-8. (c) 2017 American Cancer Society.

PMID- 28493547
TI  - Clinical trial enrollment of adolescents and young adults with sarcoma.
AB  - More than half of all sarcomas occur in adolescents and young adults (AYAs) aged
      15 to 39 years. After the publication of the AYA series in the April 1, 2016
      issue of Cancer, several leaders in the field of sarcoma across disciplines
      gathered to discuss the status of sarcoma clinical research in AYAs. They
      determined that a focused effort to include the underrepresented and understudied
      AYA population in current and future sarcoma clinical trials is overdue. Trial
      enrichment for AYA-aged sarcoma patients will produce more meaningful results
      that better represent the disease's biology, epidemiology, and treatment
      environment. To address the current deficit, this commentary outlines changes
      believed to be necessary to expediently achieve an increase in the enrollment of
      AYAs in sarcoma clinical trials. Cancer 2017;123:3434-40. (c) 2017 American
      Cancer Society.

PMID- 28493549
TI  - Transcription factor RBP-J-mediated signalling regulates basophil
      immunoregulatory function in mouse asthma model.
AB  - Basophils (BA) play an important role in the promotion of aberrant T helper type
      2 (Th2) immune responses in asthma. It is not only the effective cell, but also
      modulates the initiation of Th2 immune responses. We earlier demonstrated that
      Notch signalling regulates the biological function of BAin vitro. However,
      whether this pathway plays the same role in vivo is not clear. The purpose of the
      present study was to investigate the effect of Notch signalling on BA function in
      the regulation of allergic airway inflammation in a murine model of asthma. Bone
      marrow BA were prepared by bone marrow cell culture in the presence of
      recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of
      the CD49b+ microbeads. The recombination signal binding protein J (RBP-J-/- ) BA
      were co-cultured with T cells, and the supernatant and the T-cell subtypes were
      examined. The results indicated disruption of the capacity of BA for antigen
      presentation alongside an up-regulation of the immunoregulatory function. This
      was possibly due to the low expression of OX40L in the RBP-J-/- BA. Basophils
      were adoptively transferred to ovalbumin-sensitized recipient mice, to establish
      an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid,
      airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were
      determined. Overall, our results indicate that the RBP-J-mediated Notch
      signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J
      influences the immunoregulatory functions of BA, which include activation of T
      cells and their differentiation into T helper cell subtypes. The Notch signalling
      pathway is a potential therapeutic target for BA-based immunotherapy against
      asthma.

PMID- 28493550
TI  - Emotion Reactivity, Comfort Expressing Emotions, and Future Suicidal Ideation in
      Emerging Adults.
AB  - OBJECTIVE: Emotion reactivity and difficulties in expressing emotions have been
      implicated in risk for suicidal behavior. This study examined comfort in
      expressing emotions (positive vs. negative) and depressive symptoms as mediators
      of the prospective relation between emotion reactivity and suicidal ideation.
      DESIGN: Emerging adults (N = 143; 72% female; 28% White) completed measures of
      emotion reactivity, comfort expressing emotions, and suicidal ideation at
      baseline and of depressive symptoms and suicidal ideation 12 months later.
      RESULTS: Emotion reactivity predicted suicidal ideation at follow-up through
      depressive symptoms. Difficulty expressing love-but not happiness, sadness, and
      anger-partially mediated the relationship between emotion reactivity and suicidal
      ideation at follow-up before but not after adjusting for baseline ideation.
      CONCLUSION: The relation between high emotion reactivity and suicidal ideation
      may be explained by discomfort in the expression of positive emotions and by
      depressive symptoms. Promotion of comfort in positive emotion expression may
      reduce vulnerability to suicidal ideation.

PMID- 28493552
TI  - Multigene assays: Implications for breast cancer staging.

PMID- 28493551
TI  - Utilization of a Sobering Center for Acute Alcohol Intoxication.
AB  - OBJECTIVE: The objective was to describe the population utilizing a sobering
      center for public alcohol intoxication and compare between single-visit users,
      repeat users, and high users. METHODS: We conducted a secondary analysis of 1,271
      adults cared for in a sobering center from July 2014 to June 2015. We divided the
      population into three groups-single use (one visit), repeat users (two to five
      visits), and high (six or more) users-and evaluated demographics, lifetime health
      diagnoses utilizing the Elixhauser Comorbidity Index, rates of public service
      utilization including ambulance and emergency department, and related costs.
      RESULTS: The population was primarily male, middle-aged, and ethnically diverse.
      Compared to single-visit users (n = 869), repeat (n = 287) and high users (n =
      115) were older, were more likely to be currently homeless, and had spent more
      time homeless. Repeat and high users had significantly higher rates of
      hypertension, liver disease, diabetes, depression, psychoses, and drug abuse
      diagnoses compared to single-visit users. In addition to sobering visits,
      utilization of ambulance and ED and related costs were significantly greater for
      the high users compared to repeat and single-visit users. CONCLUSIONS: From an
      overall heterogeneous population, more frequent utilizers of the sobering center,
      both high and repeat users compared to low users, had significantly greater
      prevalence of chronic disorders, service utilization, and homelessness. Findings
      indicate that a sobering center can have a prominent role in the care for those
      with acute alcohol intoxication, particularly those individuals with chronic
      public intoxication who are likewise homeless. Further longitudinal research
      could offer important insights as to the population served over time,
      investigating changes in utilization and efforts toward health and housing
      stabilization.

PMID- 28493553
TI  - Regulation of cytokinesis during corticogenesis: focus on the midbody.
AB  - Development of the cerebral cortices depends on tight regulation of cell
      divisions. In this system, stem and progenitor cells undergo symmetric and
      asymmetric divisions to ultimately produce neurons that establish the layers of
      the cortex. Cell division culminates with the formation of the midbody, a
      transient organelle that establishes the site of abscission between nascent
      daughter cells. During cytokinetic abscission, the final stage of cell division,
      one daughter cell will inherit the midbody remnant, which can then maintain or
      expel the remnant, but mechanisms and circumstances influencing this decision are
      unclear. This review describes the midbody and its constituent proteins, as well
      as the known consequences of their manipulation during cortical development. The
      potential functional relevance of midbody mechanisms is discussed.

PMID- 28493555
TI  - Parental Secondary Stress: The Often Hidden Consequences of Nonsuicidal Self
      Injury in Youth.
AB  - OBJECTIVE: This study aims to deepen understanding of the effects on parents of
      having a self-injuring child by (a) analyzing differences in dimensions of
      caregiver strain between caregivers of youth with nonsuicidal self-injury (NSSI+)
      and parents of youth with no known mental health history (MH-); (b) identifying
      factors that contribute to caregiver strain; and (c) examining parent outcome
      expectancies. METHOD: Participants were 196 NSSI+ parents and 57 MH- parents.
      Quantitative measures of psychosocial variables, parent mental health and support
      variables, and child self-injury characteristics were assessed in relation to
      caregiver strain, and NSSI+ parental expectancies were assessed via mixed
      methods. RESULTS: Parents with a NSSI+ youth were more likely to exhibit all
      forms of objective and subjective strain than parents of youth with no mental
      health challenges. Despite this, many parents expressed beliefs that their child
      would experience personal growth as a result of their NSSI experience.
      CONCLUSION: Findings reveal the important role of mindful parenting practices and
      informal social support.

PMID- 28493556
TI  - Association of Anticipated and Laboratory-Derived Alcohol Stimulation, Sedation,
      and Reward.
AB  - BACKGROUND: Laboratory alcohol challenges are the "gold standard" for obtaining
      accurate measurements of subjective alcohol stimulation, sedation, and reward.
      However, these approaches are time and resource intensive. This study examined
      the extent to which self-reported anticipated alcohol stimulation, sedation, and
      reward corresponded with those same responses measured with the Biphasic Alcohol
      Effects Scale (BAES), Brief-BAES (B-BAES), and Drug Effects Questionnaire (DEQ)
      during a controlled laboratory alcohol challenge. METHODS: Participants were 106
      light-to-heavy social drinkers (58.5% male; mean +/- SD age = 35.8 +/- 3.2 years)
      who completed the Anticipated BAES and DEQ, as well as laboratory-derived
      versions of these scales 30 and 60 minutes after consuming placebo and 0.8 g/kg
      alcohol on separate days as part of laboratory sessions in the Chicago Social
      Drinking Project. RESULTS: Anticipated BAES/B-BAES and Anticipated DEQ alcohol
      effects were strong predictors of their corresponding laboratory-derived
      responses during both the rising limb and at peak breath alcohol concentrations.
      Effects were significant even when accounting for age, sex, past-month heavy
      drinking frequency, and laboratory session order (placebo or alcohol first).
      CONCLUSIONS: This study provides strong preliminary support for measuring
      anticipated alcohol effects with the Anticipated BAES/B-BAES and Anticipated DEQ
      as a proxy of subjective responses experienced during a controlled laboratory
      alcohol challenge. The findings lend support for these measures as viable
      alternatives to other anticipatory scales when laboratory-derived alcohol
      response measurement is not feasible.

PMID- 28493557
TI  - Couples Coping Through Deployment: Findings From a Sample of National Guard
      Families.
AB  - OBJECTIVE: Military families face numerous changes and stresses as they negotiate
      deployments and other life transitions. How they cope with these events is an
      important part of their overall well-being and resilience. This longitudinal
      study on coping in a sample of National Guard couples examined the association
      between the predeployment coping (active vs. avoidant) of each in the
      relationship, and their own and their significant others' mental health (anxiety,
      depression, posttraumatic stress disorder [PTSD]) and family well-being (dyadic
      adjustment and parenting stress) postdeployment. METHOD: A total of 238 matched
      couples completed the predeployment survey, 143 matched couples completed the
      post, with 122 matched couples completing both pre- and postdeployment surveys.
      RESULTS: While active coping was not significantly associated with any outcomes,
      predeployment avoidant coping in both soldiers and significant others was
      associated with increased anxiety, PTSD, and depression post deployment (actor
      effects). Additionally, soldier avoidant coping predeployment was associated with
      increased parenting stress for soldiers, while significant other avoidant coping
      predeployment was associated with increased relationship distress for significant
      others (actor effects). Finally, significant other avoidant coping predeployment
      was associated with higher parenting distress for soldiers postdeployment
      (partner effect). CONCLUSION: Findings suggest that interventions are needed to
      combat avoidant coping (behavioral disengagement, denial, substance abuse)
      predeployment because this way of coping is strongly related to negative
      outcomes. In addition, those who work clinically with these families should work
      to reduce avoidant coping strategies and any familial dynamics exacerbated by
      this way of coping.

PMID- 28493558
TI  - Comparison of risk of malignancy in a subgroup with atypia of undetermined
      significance/follicular lesion of undetermined significance: A meta-analysis.
AB  - BACKGROUND: As heterogeneous findings are included in the atypia of undetermined
      significance (AUS)/follicular lesion of undetermined significance (FLUS)
      category, differing risks of malignancy in subgroups have been reported in
      several articles. METHODS: We performed a meta-analysis of full-text publications
      written in English found in the Embase and PubMed databases. RESULTS: The 4
      tiered subgroup proportion meta-analysis showed that the 95% confidence interval
      (95% CI) of the risk of malignancy in the cellular atypia group did not overlap
      with the other 3 subgroups and demonstrated a significant difference. Two-tiered
      analysis using the cytologic and architectural atypia groups showed that
      cytologic atypia group had a 2.64-fold increase in the risk of malignancy
      compared with the architectural atypia group. CONCLUSION: The cytologic atypia
      had a significantly higher risk of malignancy than the architectural atypia
      group, and it should be considered as a separate category.

PMID- 28493561
TI  - Distress, omnipotence, and responsibility beliefs in command hallucinations.
AB  - OBJECTIVES: Command hallucinations are considered to be one of the most
      distressing and disturbing symptoms of schizophrenia. Building on earlier
      studies, we compare key attributes in the symptomatic, affective, and cognitive
      profiles of people diagnosed with schizophrenia and hearing voices that do (n =
      77) or do not (n = 74) give commands. METHODS: The study employed a cross
      sectional design, in which we assessed voice severity, distress and control
      (PSYRATs), anxiety and depression (HADS), beliefs about voices (BAVQ-R), and
      responsibility beliefs (RIQ). Clinical and demographic variables were also
      collected. RESULTS: Command hallucinations were found to be more distressing and
      controlling, perceived as more omnipotent and malevolent, linked to higher
      anxiety and depression, and resisted more than hallucinations without commands.
      Commanding voices were also associated with higher conviction ratings for being
      personally responsible for preventing harm. CONCLUSIONS: The findings suggest key
      differences in the affective and cognitive profiles of people who hear commanding
      voices, which have important implications for theory and psychological
      interventions. PRACTITIONER POINTS: Command hallucinations are associated with
      higher distress, malevolence, and omnipotence. Command hallucinations are
      associated with higher responsibility beliefs for preventing harm. Responsibility
      beliefs are associated with voice-related distress. Future psychological
      interventions for command hallucinations might benefit from focussing not only on
      omnipotence, but also on responsibility beliefs, as is done in psychological
      therapies for obsessive compulsive disorder. Limitations The cross-sectional
      design does not assess issues of causality. We did not measure the presence or
      severity of delusions.

PMID- 28493562
TI  - Perioperative practices in thyroid surgery: An international survey.
AB  - BACKGROUND: Perioperative practices in thyroid surgery vary from one specialty,
      institution, or country to the next. We evaluated the preoperative,
      intraoperative, and postoperative practices of thyroid surgeons focusing on
      preoperative ultrasound, vocal cord evaluation, wound drains, and hospitalization
      duration, among others. METHODS: A survey was sent to 7 different otolaryngology
      and endocrine/general surgery associations. RESULTS: There were 965 respondents
      from 52 countries. Surgeon-performed ultrasound is practiced by more than one
      third of respondents. Otolaryngologists perform preoperative and postoperative
      vocal cord evaluation more often than endocrine/general surgeons (p < .001).
      Sixty percent of respondents either never place drains or place drains <50% of
      the time in thyroid lobectomies (43% for total thyroidectomies). Outpatient
      thyroid surgery is most frequently performed by surgeons in the United States
      (63%). CONCLUSION: This epidemiologic study is the first global thyroid survey of
      its kind and clearly demonstrates the variability and evolving trends in thyroid
      surgery. (c) 2017 Wiley Periodicals, Inc. Head Neck 39: 1296-1305, 2017.

PMID- 28493559
TI  - mTOR referees memory and disease through mRNA repression and competition.
AB  - Mammalian target of rapamycin (mTOR) activity is required for memory and is
      dysregulated in disease. Activation of mTOR promotes protein synthesis; however,
      new studies are demonstrating that mTOR activity also represses the translation
      of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that
      memory was due to the induction of positive regulators and removal of negative
      constraints. Are these negative constraints repressed mRNAs that code for
      proteins that block memory formation? Herein, we will discuss the mRNAs coded by
      putative memory suppressors, how activation/inactivation of mTOR repress protein
      expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA
      stability, and translation, and what the possible implications of mRNA repression
      are to memory and neurodegenerative disorders.

PMID- 28493563
TI  - Nalmefene Prevents Alcohol-Induced Neuroinflammation and Alcohol Drinking
      Preference in Adolescent Female Mice: Role of TLR4.
AB  - BACKGROUND: We previously showed that, by activating innate immune receptors Toll
      like 4 (TLR4), adolescent intermittent ethanol (EtOH) exposure causes
      neuroinflammation, myelin damage, and behavioral dysfunctions. Recent findings
      reveal that clinically used opioid antagonists naltrexone (NT) and naloxone (NX)
      inhibit opioid-induced TLR4 signaling and that NT, NX, and nalmefene (NF), the 6
      methylene derivative of NX, are able to reduce alcohol drinking escalation.
      METHODS: NF (0.1 mg/kg, intraperitoneally) was injected 1 hour prior to EtOH (3
      g/kg, intraperitoneally) following intermittent treatment in female (PND35)
      adolescent mice. Inflammatory molecules, myelin proteins, and apoptotic markers
      were assessed in the prefrontal cortex (PFC) and striatum/nucleus accumbens
      (STR/NAcc). The effect of NF on alcohol drinking preference was evaluated in both
      the wild-type and TLR4 knockout (KO) adolescent mice. Using astroglial cells, the
      inhibitory potential of NT, NX, and NF on lipopolysaccharide (LPS), or the EtOH
      triggered TLR4 response, was compared. RESULTS: Our findings indicate that NF
      prevents the up-regulation of cytokines (IL-1beta, IL-17A, TNF-alpha), chemokines
      (MCP-1, MIP-1, KC), and pro-inflammatory mediators (iNOS, COX-2), along with
      myelin damage and apoptotic events, in both PFC and STR/NAcc. NF also abolishes
      EtOH-induced escalation of alcohol preference/consumption, but has no effect when
      administered to TLR4-KO mice. In vitro experiments indicate that NX and NF
      inhibit TLR4 activation upon LPS or EtOH stimulation. Immunofluorescence studies
      and lipid rafts isolation show that NF is able to prevent TLR4 translocation to
      lipid rafts/caveolae in astrocytes. CONCLUSIONS: These results suggest that NF
      prevents neuroinflammation and brain damage by blocking the TLR4 response and
      also support the role of central pro-inflammatory immune signaling in the
      modulation of alcohol consumption/addiction.

PMID- 28493565
TI  - A new simple iterative reconstruction algorithm for SPECT transmission
      measurement.
AB  - This paper proposes a new iterative reconstruction algorithm for transmission
      tomography and compares this algorithm with several other methods. The new
      algorithm is simple and resembles the emission ML-EM algorithm in form. Due to
      its simplicity, it is easy to implement and fast to compute a new update at each
      iteration. The algorithm also always guarantees non-negative solutions.
      Evaluations are performed using simulation studies and real phantom data.
      Comparisons with other algorithms such as convex, gradient, and logMLEM show that
      the proposed algorithm is as good as others and performs better in some cases.

PMID- 28493566
TI  - Confirmation, refinement, and extension of a study in intrafraction motion
      interplay with sliding jaw motion.
AB  - The interplay between a constant scan speed and intrafraction oscillatory motion
      produces interesting fluence intensity modulations along the axis of motion that
      are sensitive to the motion function, as originally shown in a classic paper by
      Yu et al. [Phys. Med. Biol. 43, 91-104 (1998)]. The fluence intensity profiles
      are explored in this note for an intuitive understanding, then compared with Yu
      et al., and finally further explored for the effects of low scan speed and random
      components of both intrafraction and interfraction motion. At slow scan speeds
      typical of helical tomotherapy, these fluence intensity modulations are only a
      few percent. With the addition of only a small amount of cycle-to-cycle
      randomness in frequency and amplitude, the fluence intensity profiles change
      dramatically. It is further shown that after a typical 30-fraction treatment, the
      sensitivities displayed in the single fraction fluence intensity profiles greatly
      diminish.

PMID- 28493568
TI  - A packed building-block compensator (TETRIS-RT) and feasibility for IMRT
      delivery.
AB  - A packed building-block compensator (TETRIS-RT) for IMRT (Intensity Modulated
      Radiation Therapy) delivery has been proposed. The compensator contains two kinds
      of cubic blocks: x-ray absorbing blocks for intensity modulation and x-ray
      transparent blocks for packing. The packed blocks are placed inside a rectangular
      enclosure, and the resulting compensators can be attached to a linac gantry head
      through a rotatable mount for efficient multiportal IMRT. A fabrication device
      and a sorting device were also developed. The fabrication device can
      automatically stack two different types of blocks to produce a compensator while
      the sorting device can separate each type of the blocks for subsequent
      fabrication. Preliminary film experiments have shown that an additional leakage
      dose through the rounded edges of the ten-layered x-ray absorbing blocks was 0.9%
      of the delivered dose with a total shielded dose ratio of 10% including the peak
      leakage. It was observed that the proposed compensator may provide a highly
      modulated dose distribution. This suggests its feasibility for IMRT delivery with
      a limit of 1cm*1cm spatial resolution at isocenter in the plane perpendicular to
      the beam, and larger discrete intensity steps of approximately 10% compared to
      conventional compensators. Advantages of the proposed compensator include that
      the compensator blocks are reusable and can be utilized to automatically and
      quickly fabricate a compensator, thereby minimizing human labor.

PMID- 28493567
TI  - Semiautomated four-dimensional computed tomography segmentation using deformable
      models.
AB  - The purpose of this work is to demonstrate a proof of feasibility of the
      application of a commercial prototype deformable model algorithm to the problem
      of delineation of anatomic structures on four-dimensional (4D) computed
      tomography (CT) image data sets. We acquired a 4D CT image data set of a
      patient's thorax that consisted of three-dimensional (3D) image data sets from
      eight phases in the respiratory cycle. The contours of the right and left lungs,
      cord, heart, and esophagus were manually delineated on the end inspiration data
      set. An interactive deformable model algorithm, originally intended for deforming
      an atlas-based model surface to a 3D CT image data set, was applied in an
      automated fashion. Triangulations based on the contours generated on each phase
      were deformed to the CT data set on the succeeding phase to generate the contours
      on that phase. Deformation was propagated through the eight phases, and the
      contours obtained on the end inspiration data set were compared with the original
      manually delineated contours. Structures defined by high-density gradients, such
      as lungs, cord, and heart, were accurately reproduced, except in regions where
      other gradient boundaries may have confused the algorithm, such as near bronchi.
      The algorithm failed to accurately contour the esophagus, a soft-tissue structure
      completely surrounded by tissue of similar density, without manual interaction.
      This technique has the potential to facilitate contour delineation in 4D CT image
      data sets; and future evolution of the software is expected to improve the
      process.

PMID- 28493569
TI  - Comparison of Monte Carlo calculations around a Fletcher Suit Delclos ovoid with
      radiochromic film and normoxic polymer gel dosimetry.
AB  - The Fletcher Suit Delclos (FSD) ovoids employed in intracavitary brachytherapy
      (ICB) for cervical cancer contain shields to reduce dose to the bladder and
      rectum. Many treatment planning systems (TPS) do not include the shields and
      other ovoid structures in the dose calculation. Instead, TPSs calculate dose by
      summing the dose contributions from the individual sources and ignoring ovoid
      structures such as the shields. The goal of this work was to calculate the dose
      distribution with Monte Carlo around a Selectron FSD ovoid and compare these
      calculations with radiochromic film (RCF) and normoxic polymer gel dosimetry.
      Monte Carlo calculations were performed with MCNPX 2.5.c for a single Selectron
      FSD ovoid with and without shields. RCF measurements were performed in a plane
      parallel to and displaced laterally 1.25 cm from the long axis of the ovoid.
      MAGIC gel measurements were performed in a polymethylmethacrylate phantom. RCF
      and MAGIC gel were irradiated with four 33MUGym2h-1 Cs-137 pellets for a period
      of 24 h. Results indicated that MCNPX calculated dose to within +/-2% or 2 mm for
      98% of points compared with RCF measurements and to within +/-3% or 3 mm for 98%
      of points compared with MAGIC gel measurements. It is concluded that MCNPX 2.5.c
      can calculate dose accurately in the presence of the ovoid shields, that RCF and
      MAGIC gel can demonstrate the effect of ovoid shields on the dose distribution
      and the ovoid shields reduce the dose by as much as 50%.

PMID- 28493570
TI  - Use of simulated annealing for optimization of alignment parameters in limited
      MRI acquisition volumes of the brain.
AB  - Studies suggest that clinical outcomes are improved in repeat trigeminal
      neuralgia (TN) Gamma Knife radiosurgery if a different part of the nerve from the
      previous radiosurgery is treated. The MR images taken in the first and repeat
      radiosurgery need to be coregistered to map the first radiosurgery volume onto
      the second treatment planning image. We propose a fully automatic and robust
      three-dimensional (3-D) mutual information- (MI-) based registration method
      engineered by a simulated annealing (SA) optimization technique. Commonly,
      Powell's method and Downhill simplex (DS) method are most popular in optimizing
      the MI objective function in medical image registration applications. However,
      due to the nonconvex property of the MI function, robustness of those two methods
      is questionable, especially for our cases, where only 28 slices of MR T1 images
      were utilized. Our SA method obtained successful registration results for all the
      41 patients recruited in this study. On the other hand, Powell's method and the
      DS method failed to provide satisfactory registration for 11 patients and 9
      patients, respectively. The overlapping volume ratio (OVR) is defined to quantify
      the degree of the partial volume overlap between the first and second MR scan.
      Statistical results from a logistic regression procedure demonstrated that the
      probability of a success of Powell's method tends to decrease as OVR decreases.
      The rigid registration with Powell's or the DS method is not suitable for the TN
      radiosurgery application, where OVR is likely to be low. In summary, our
      experimental results demonstrated that the MI-based registration method with the
      SA optimization technique is a robust and reliable option when the number of
      slices in the imaging study is limited.

PMID- 28493571
TI  - Dose perturbations due to contrast medium and air in MammoSite(r) treatment: An
      experimental and Monte Carlo study.
AB  - In the management of early breast cancer, a partial breast irradiation technique
      called MammoSite(r) (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated
      in recent years. In MammoSite, a balloon implanted at the surgical cavity during
      tumor excision is filled with a radio-opaque solution, and radiation is delivered
      via a high dose rate brachytherapy source situated at the center of the balloon.
      Frequently air may be introduced during placement of the balloon and/or injection
      of the contrast solution into the balloon. The purpose of this work is to
      quantify as well as to understand dose perturbations due to the presence of a
      high-Z contrast medium and/or an air bubble with measurements and Monte Carlo
      calculations. In addition, the measured dose distribution is compared with that
      obtained from a commercial treatment planning system (Nucletron PLATO system).
      For a balloon diameter of 42 mm, the dose variation as a function of distance
      from the balloon surface is measured for various concentrations of a radio-opaque
      solution (in the range 5%-25% by volume) with a small volume parallel plate ion
      chamber and a micro-diode detector placed perpendicular to the balloon axis.
      Monte Carlo simulations are performed to provide a basic understanding of the
      interaction mechanism and the magnitude of dose perturbation at the interface
      near balloon surface. Our results show that the radio-opaque concentration
      produces dose perturbation up to 6%. The dose perturbation occurs mostly within
      the distances <1mm from the balloon surface. The Plato system that does not
      include heterogeneity correction may be sufficient for dose planning at distances
      ?10mm from the balloon surface for the iodine concentrations used in the
      MammoSite procedures. The dose enhancement effect near the balloon surface (<1mm)
      due to the higher iodine concentration is not correctly predicted by the Plato
      system. The dose near the balloon surface may be increased by 0.5%percm3 of air.
      Monte Carlo simulation suggests that the interface effect (enhanced dose near
      surface) is primarily due to Compton electrons of short range (<0.5mm). For more
      accurate dosimetry in MammoSite delivery, the dose perturbation due to the
      presence of a radio-opaque contrast medium and air bubbles should be considered
      in a brachytherapy planning system.

PMID- 28493572
TI  - Effect of motion on tracer activity determination in CT attenuation corrected PET
      images: A lung phantom study.
AB  - Respiratory motion is known to affect the quantitation of FDG18 uptake in lung
      lesions. The aim of the study was to investigate the magnitude of errors in
      tracer activity determination due to motion, and its dependence upon CT
      attenuation at different phases of the motion cycle. To estimate these errors we
      have compared maximum activity concentrations determined from PET/CT images of a
      lung phantom at rest and under simulated respiratory motion. The NEMA 2001 IEC
      body phantom, containing six hollow spheres with diameters 37, 28, 22, 17, 13,
      and 10 mm, was used in this study. To mimic lung tissue density, the phantom
      (excluding spheres) was filled with low density polystyrene beads and water. The
      phantom spheres were filled with FDG18 solution setting the target-to-background
      activity concentration ratio at 8:1. PET/CT data were acquired with the phantom
      at rest, and while it was undergoing periodic motion along the longitudinal axis
      of the scanner with a range of displacement being 2 cm, and a period of 5 s. The
      phantom at rest and in motion was scanned using manufacturer provided standard
      helical/clinical protocol, a helical CT scan followed by a PET emission scan. The
      moving phantom was also scanned using a 4D-CT protocol that provides volume image
      sets at different phases of the motion cycle. To estimate the effect of motion on
      quantitation of activities in six spheres, we have examined the activity
      concentration data for (a) the stationary phantom, (b) the phantom undergoing
      simulated respiratory motion, and (c) a moving phantom acquired with PET/4D-CT
      protocol in which attenuation correction was performed with CT images acquired at
      different phases of motion cycle. The data for the phantom at rest and in motion
      acquired with the standard helical/clinical protocol showed that the activity
      concentration in the spheres can be underestimated by as much as 75%, depending
      on the sphere diameter. We have also demonstrated that fluctuations in sphere's
      activity concentration from one PET/CT scan to another acquired with standard
      helical/clinical protocol can arise as a consequence of spatial mismatch between
      the sphere's location in PET emission and the CT data.

PMID- 28493573
TI  - The applicability of simultaneous TRUS-CT imaging for the evaluation of prostate
      seed implants.
AB  - To study dose-effect relations of prostate implants with I-125 seeds, accurate
      knowledge of the dose distribution in the prostate is essential. Commonly, a post
      implant computed tomography (CT) scan is used to determine the geometry of the
      implant and to delineate the contours of the prostate. However, the delineation
      of the prostate on CT slices is very cumbersome due to poor contrast between the
      prostate capsule and surrounding tissues. Transrectal Ultrasound (TRUS) on the
      other hand offers good visualization of the prostate but poor visualization of
      the implanted seeds. The purpose of this study was to investigate the
      applicability of combining CT with 3D TRUS by means of image fusion. The
      advantage of fused TRUS-CT imaging is that both prostate contours and implanted
      seeds will be well visible. In our clinic, post-implant imaging was realized by
      simultaneously acquiring a TRUS scan and a CT scan. The TRUS transducer was
      inserted while the patient was on the CT couch and the CT scan was made directly
      after the TRUS scan, with the probe still in situ. With the TRUS transducer being
      visible on both TRUS and CT images, the geometrical relationship between both
      image sets could be defined by registration on the transducer. Having proven the
      applicability of simultaneous imaging, the accuracy of this registration method
      was investigated by additional registration on visible seeds, after
      preregistration on the transducer. In 4 out of 23 investigated cases an automatic
      grey value registration on seeds failed for each of the investigated cost
      functions, and in 2 cases for both cost functions, due to poor visibility of the
      seeds on the TRUS scan. The average deviations of the seed registration with
      respect to the transducer registration were negligible. However, in a few
      individual cases the deviations were significant and probably due to movement of
      the patient between TRUS and CT scan. In case of a registration on the transducer
      it is important to avoid patient movement in-between the TRUS and CT scan and to
      keep the time in-between the scans as short as possible. It can be concluded that
      fusion of a CT scan and a simultaneously made TRUS scan by means of a three
      dimensional (3D) transducer is feasible and accurate when performing a
      registration on the transducer, if necessary, fine-tuned by a registration on
      seeds. These fused images are likely to be of great value for post-implant dose
      distribution evaluations.

PMID- 28493574
TI  - Precise radiochromic film dosimetry using a flat-bed document scanner.
AB  - In this study, a measurement protocol is presented that improves the precision of
      dose measurements using a flat-bed document scanner in conjunction with two new
      GafChromic(r) film models, HS and Prototype A EBT exposed to 6MV photon beams. We
      established two sources of uncertainties in dose measurements, governed by
      measurement and calibration curve fit parameters contributions. We have
      quantitatively assessed the influence of different steps in the protocol on the
      overall dose measurement uncertainty. Applying the protocol described in this
      paper on the Agfa Arcus II flat-bed document scanner, the overall one-sigma dose
      measurement uncertainty for an uniform field amounts to 2% or less for doses
      above around 0.4Gy in the case of the EBT (Prototype A), and for doses above 5Gy
      in the case of the HS model GafChromic(r) film using a region of interest 2*2mm2
      in size.

PMID- 28493575
TI  - Characterization and correction of temporal artifacts in CT.
AB  - Image artifacts, caused by a temporally delayed response of a computed tomography
      (CT) detector, were investigated. To study its consequences, a computer model for
      a standard third generation CT scanner was devised and simulations were carried
      out. Resulting image artifacts were studied for various voxel-based and
      mathematical phantoms using three time constants, which characterize the delayed
      signal responses of different detector configurations. Furthermore, a theory was
      developed to understand temporal artifacts in reconstructed images. A filter
      function was derived, which compensates for temporal artifacts. For a given
      phantom, simulations and theory demonstrate that artifacts scale with the time
      constant, characteristic for the detector, and the angular speed of the scanner.

PMID- 28493576
TI  - Measurement of the detective quantum efficiency in digital detectors consistent
      with the IEC 62220-1 standard: Practical considerations regarding the choice of
      filter material.
AB  - As part of a larger evaluation we attempted to measure the detective quantum
      efficiency (DQE) of an amorphous silicon flat-panel detector using the method
      described in the International Electrotechnical Commission standard 62220-1
      published in October 2003. To achieve the radiographic beam conditions specified
      in the standard, we purchased scientific-grade ultrahigh purity aluminum (99.999%
      purity, type-11999 alloy) filters in thicknesses ranging from 0.1 through 10.0 mm
      from a well-known, specialty metals supplier. Qualitative evaluation of flat
      field images acquired at 71 kV (RQA5 beam quality) with 21 mm of ultrahigh purity
      aluminum filtration demonstrated a low frequency mottle that was reproducible and
      was not observed when the measurement was repeated at 74 kV (RQA5 beam quality)
      with 21 mm of lower-purity aluminum (99.0% purity, type-1100 alloy) filtration.
      This finding was ultimately attributed to the larger grain size (approximately 1
      2 mm) of high purity aluminum metal, which is a well-known characteristic,
      particularly in thicknesses greater than 1 mm. The impact of this low frequency
      mottle is to significantly overestimate the noise power spectrum (NPS) at spatial
      frequencies ?0.2mm-1, which in turn would cause an underestimation of the DQE in
      this range. A subsequent evaluation of ultrahigh purity aluminum, purchased from
      a second source, suggests, that reduced grain size can be achieved by the process
      of annealing. Images acquired with this sample demonstrated vertical striated
      nonuniformities that are attributed to the manufacturing method and which do not
      appear to appreciably impact the NPS at spatial frequencies ?0.5mm-1, but do
      result in an asymmetry in the x- and y-NPS at spatial frequencies ?0.2mm-1. Our
      observations of markedly visible nonuniformities in images acquired with high
      purity aluminum filtration suggest that the uniformity of filter materials should
      be carefully evaluated and taken into consideration when measuring the DQE.

PMID- 28493577
TI  - Design and application of an assessment protocol for electromagnetic tracking
      systems.
AB  - This paper defines a simple protocol for competitive and quantified evaluation of
      electromagnetic tracking systems such as the NDI Aurora (A) and Ascension
      microBIRD with dipole transmitter (B). It establishes new methods and a new
      phantom design which assesses the reproducibility and allows comparability with
      different tracking systems in a consistent environment. A machined base plate was
      designed and manufactured in which a 50 mm grid of holes was precisely drilled
      for position measurements. In the center a circle of 32 equispaced holes enables
      the accurate measurement of rotation. The sensors can be clamped in a small mount
      which fits into pairs of grid holes on the base plate. Relative
      positional/orientational errors are found by subtracting the known
      distances/rotations between the machined locations from the differences of the
      mean observed positions/rotation. To measure the influence of metallic objects we
      inserted rods made of steel (SST 303, SST 416), aluminum, and bronze into the
      sensitive volume between sensor and emitter. We calculated the fiducial
      registration error and fiducial location error with a standard stylus calibration
      for both tracking systems and assessed two different methods of stylus
      calibration. The positional jitter amounted to 0.14 mm(A) and 0.08 mm(B). A
      relative positional error of 0.96mm+/-0.68mm, range -0.06 mm; 2.23 mm(A) and
      1.14mm+/-0.78mm, range -3.72 mm; 1.57 mm(B) for a given distance of 50 mm was
      found. The relative rotation error was found to be 0.51 degrees  (A)/0.04 degrees
      (B). The most relevant distortion caused by metallic objects results from SST
      416. The maximum error 4.2mm(A)/?100mm(B) occurs when the rod is close to the
      sensor(20 mm). While (B) is more sensitive with respect to metallic objects, (A)
      is less accurate concerning orientation measurements. (B) showed a systematic
      error when distances are calculated.

PMID- 28493578
TI  - Internal radionuclide therapy: The ULMDOS software for treatment planning.
AB  - Before therapy with unsealed radionuclides, a dosimetry assessment must be
      performed for each patient. We present the interactive software tool ULMDOS,
      which facilitates dosimetric calculations, enhances traceability, and adequate
      documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under
      Windows XP/2000. First the patient data, the radiotracer data, and optionally
      urine and serum data are entered. After loading planar gamma camera images and
      drawing regions of interest, the residence times can be calculated using fits of
      the time activity data to exponential functions. Data can be saved in ASCII
      format for retrospective examination and further processing. ULMDOS allows one to
      process the dosimetric calculations within a standardized environment, spares the
      time-consuming transfer of data between different software tools, enables the
      documentation of ROI and raw data, and reduces intraindividual variability.
      ULMDOS satisfies the required conditions for traceability and documentation as a
      prerequisite to routine use in clinical settings.

PMID- 28493579
TI  - Investigation of psychophysical measure for evaluation of similar images for
      mammographic masses: Preliminary results.
AB  - We investigated a psychophysical similarity measure for selection of images
      similar to those of unknown masses on mammograms, which may assist radiologists
      in the distinction between benign and malignant masses. Sixty pairs of masses
      were selected from 1445 mass images prepared for this study, which were obtained
      from the Digital Database for Screening Mammography by the University of South
      Florida. Five radiologists provided subjective similarity ratings for these 60
      pairs of masses based on the overall impression for diagnosis. Radiologists'
      subjective ratings were marked on a continuous rating scale and quantified
      between 0 and 1, which correspond to pairs not similar at all and pairs almost
      identical, respectively. By use of the subjective ratings as "gold standard,"
      similarity measures based on the Euclidean distance between pairs in feature
      space and the psychophysical measure were determined. For determination of the
      psychophysical similarity measure, an artificial neural network (ANN) was
      employed to learn the relationship between radiologists' average subjective
      similarity ratings and computer-extracted image features. To evaluate the
      usefulness of the similarity measures, the agreement with the radiologists'
      subjective similarity ratings was assessed in terms of correlation coefficients
      between the average subjective ratings and the similarity measures. A commonly
      used similarity measure based on the Euclidean distance was moderately correlated
      (r=0.644) with the radiologists' average subjective ratings, whereas the
      psychophysical measure by use of the ANN was highly correlated (r=0.798). The
      preliminary result indicates that a psychophysical similarity measure would be
      useful in the selection of images similar to those of unknown masses on
      mammograms.

PMID- 28493580
TI  - On the efficiency of photon beam treatment head simulations.
AB  - The paper presents a theoretical derivation of the photon fluence simulation
      efficiency in photon beam treatment head simulations without and with
      bremsstrahlung splitting. The expressions obtained provide a rigorous explanation
      of the efficiency dependence on scoring zone size and splitting number and
      explain the larger efficiency of the directional bremsstrahlung splitting
      technique compared to uniform bremsstrahlung splitting. They are also very useful
      for determining the optimum splitting number in practical treatment head
      simulations and for understanding the variation of simulation efficiency with
      beam energy and field size.

PMID- 28493581
TI  - Comparison of spirometry and abdominal height as four-dimensional computed
      tomography metrics in lung.
AB  - An important consideration in four-dimensional CT scanning is the selection of a
      breathing metric for sorting the CT data and modeling internal motion. This study
      compared two noninvasive breathing metrics, spirometry and abdominal height,
      against internal air content, used as a surrogate for internal motion. Both
      metrics were shown to be accurate, but the spirometry showed a stronger and more
      reproducible relationship than the abdominal height in the lung. The abdominal
      height was known to be affected by sensor placement and patient positioning while
      the spirometer exhibited signal drift. By combining these two, a normalization of
      the drift-free metric to tidal volume may be generated and the overall metric
      precision may be improved.

PMID- 28493582
TI  - The use of phase sequence image sets to reconstruct the total volume occupied by
      a mobile lung tumor.
AB  - The use of phase sequence image (PSI) sets to reveal the total volume occupied by
      a mobile target is presented. Isocontrast composite clinical target volumes
      (CCTVs) may be constructed from PSI sets in order to reveal the total volume
      occupied by a mobile target during the course of its travel. The ability of the
      CCTV technique to properly account for target motion is demonstrated by
      comparison to contours of the true total volume occupied (TVO) for a number of
      experimental phantom geometries. Finally, using real patient data, the clinical
      utility of the CCTV technique to properly account for internal tumor motion while
      minimizing the volume of healthy lung tissue irradiated is assessed by comparison
      to the standard approach of applying safety margins. Results of the phantom study
      reveal that CCTV cross sections constructed at the 20% isocontrast level yield
      good agreement with the total cross sections (TXO) of mobile targets. These CCTVs
      conform well to the TVOs of the moving targets examined whereby the addition of
      small uniform margins ensures complete circumscription of the TVO with the
      inclusion of minimal amounts of surrounding external volumes. The CCTV technique
      is seen to be clearly superior to the common practice of the addition of safety
      margins to individual CTV contours in order to account for internal target
      motion. Margins required with the CCTV technique are eight to ten times smaller
      than those required with individual CTVs.

PMID- 28493583
TI  - Robust x-ray tubes for use within magnetic fields of MR scanners.
AB  - A hybrid system that combines an x-ray fluoroscopic system and a magnetic
      resonance (MR) system can provide physicians with the synergy of exquisite soft
      tissue contrast (from MR) and high temporal and spatial resolutions (from x ray),
      which may significantly benefit a number of image-guided interventional
      procedures. However, the system configuration may require the x-ray tube to be
      placed in a magnetic field, which can hinder the proper functioning of the x-ray
      tube by deflecting its electron beam. From knowledge of how the magnetic field
      affects the electron trajectories, we propose creating another magnetic field
      along the cathode-anode axis using either solenoids or permanent magnets to
      reduce the deflection of the electron beam for two cases: a strong and slightly
      misaligned field or a weak field that is arbitrary in direction. Theoretical
      analysis is presented and the electron beam is simulated in various external
      magnetic fields with a finite element modeling program. Results show that both
      correction schemes enhance the robustness of the x-ray tube operation in an
      externally applied magnetic field.

PMID- 28493584
TI  - Intracranial stereotactic positioning systems: Report of the American Association
      of Physicists in Medicine Radiation Therapy Committee Task Group No. 68.
AB  - Intracranial stereotactic positioning systems (ISPSs) are used to position
      patients prior to precise radiation treatment of localized lesions of the brain.
      Often, the lesion is located in close proximity to critical anatomic features
      whose functions should be maintained. Many types of ISPSs have been described in
      the literature and are commercially available. These are briefly reviewed. ISPS
      systems provide two critical functions. The first is to establish a coordinate
      system upon which a guided therapy can be applied. The second is to provide a
      method to reapply the coordinate system to the patient such that the coordinates
      assigned to the patient's anatomy are identical from application to application.
      Without limiting this study to any particular approach to ISPSs, this report
      introduces nomenclature and suggests performance tests to quantify both the
      stability of the ISPS to map diagnostic data to a coordinate system, as well as
      the ISPS's ability to be realigned to the patient's anatomy. For users who desire
      to develop a new ISPS system, it may be necessary for the clinical team to
      establish the accuracy and precision of each of these functions. For commercially
      available systems that have demonstrated an acceptable level of accuracy and
      precision, the clinical team may need to demonstrate local ability to apply the
      system in a manner consistent with that employed during the published testing.
      The level of accuracy and precision required of an individual ISPS system is
      dependent upon the clinical protocol (e.g., fractionation, margin, pathology,
      etc.). Each clinical team should provide routine quality assurance procedures
      that are sufficient to support the assumptions of accuracy and precision used
      during the planning process. The testing of ISPS systems can be grouped into two
      broad categories, type testing, which occurs prior to general commercialization,
      and site testing, performed when a commercial system is installed at a clinic.
      Guidelines to help select the appropriate tests as well as recommendations to
      help establish the required frequency of testing are provided. Because of the
      broad scope of different systems, it is important that both the manufacturer and
      user rigorously critique the system and set QA tests appropriate to the
      particular device and its possible weaknesses. Major recommendations of the Task
      Group include: introduction of a new nomenclature for reporting repositioning
      accuracy; comprehensive analysis of patient characteristics that might adversely
      affect positioning accuracy; performance of testing immediately before each
      treatment to establish that there are no gross positioning errors; a general
      request to the Medical Physics community for improved QA tools; implementation of
      weekly portal imaging (perhaps cone beam CT in the future) as a method of
      tracking fractionated patients (as per TG 40); and periodic routine reviews of
      positioning accuracy.

PMID- 28493585
TI  - Partial volume segmentation of brain magnetic resonance images based on maximum a
      posteriori probability.
AB  - Noise, partial volume (PV) effect, and image-intensity inhomogeneity render a
      challenging task for segmentation of brain magnetic resonance (MR) images. Most
      of the current MR image segmentation methods focus on only one or two of the
      above-mentioned effects. The objective of this paper is to propose a unified
      framework, based on the maximum a posteriori probability principle, by taking all
      these effects into account simultaneously in order to improve image segmentation
      performance. Instead of labeling each image voxel with a unique tissue type, the
      percentage of each voxel belonging to different tissues, which we call a mixture,
      is considered to address the PV effect. A Markov random field model is used to
      describe the noise effect by considering the nearby spatial information of the
      tissue mixture. The inhomogeneity effect is modeled as a bias field characterized
      by a zero mean Gaussian prior probability. The well-known fuzzy C-mean model is
      extended to define the likelihood function of the observed image. This framework
      reduces theoretically, under some assumptions, to the adaptive fuzzy C-mean
      (AFCM) algorithm proposed by Pham and Prince. Digital phantom and real clinical
      MR images were used to test the proposed framework. Improved performance over the
      AFCM algorithm was observed in a clinical environment where the inhomogeneity,
      noise level, and PV effect are commonly encountered.

PMID- 28493586
TI  - Plastic scintillation dosimetry: Optimal selection of scintillating fibers and
      scintillators.
AB  - Scintillation dosimetry is a promising avenue for evaluating dose patterns
      delivered by intensity-modulated radiation therapy plans or for the small fields
      involved in stereotactic radiosurgery. However, the increase in signal has been
      the goal for many authors. In this paper, a comparison is made between plastic
      scintillating fibers and plastic scintillator. The collection of scintillation
      light was measured experimentally for four commercial models of scintillating
      fibers (BCF-12, BCF-60, SCSF-78, SCSF-3HF) and two models of plastic
      scintillators (BC-400, BC-408). The emission spectra of all six scintillators
      were obtained by using an optical spectrum analyzer and they were compared with
      theoretical behavior. For scintillation in the blue region, the signal intensity
      of a singly clad scintillating fiber (BCF-12) was 120% of that of the plastic
      scintillator (BC-400). For the multiclad fiber (SCSF-78), the signal reached 144%
      of that of the plastic scintillator. The intensity of the green scintillating
      fibers was lower than that of the plastic scintillator: 47% for the singly clad
      fiber (BCF-60) and 77% for the multiclad fiber (SCSF-3HF). The collected light
      was studied as a function of the scintillator length and radius for a cylindrical
      probe. We found that symmetric detectors with nearly the same spatial resolution
      in each direction (2 mm in diameter by 3 mm in length) could be made with a
      signal equivalent to those of the more commonly used asymmetric scintillators.
      With augmentation of the signal-to-noise ratio in consideration, this paper
      presents a series of comparisons that should provide insight into selection of a
      scintillator type and volume for development of a medical dosimeter.

PMID- 28493587
TI  - Image-guided adaptive radiation therapy (IGART): Radiobiological and dose
      escalation considerations for localized carcinoma of the prostate.
AB  - The goal of this work was to evaluate the efficacy of various image-guided
      adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the
      prostate in the presence of geometric uncertainties. Five prostate patients with
      15-16 treatment CT studies each were retrospectively analyzed. All patients were
      planned with an 18 MV, six-field conformal technique with a 10 mm margin size and
      an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed
      in this work for patient-specific dose escalation was to increase the
      prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue
      complication probability (NTCP) reached a level equal to that of the nominal plan
      NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques
      simulated were: (1) daily laser-guided alignment to skin tattoo marks that
      represents treatment without image-guidance, (2) alignment to bony landmarks with
      daily portal images, and (3) alignment to the clinical target volume (CTV) with
      daily CT images. Techniques (1) and (3) were resimulated with a reduced margin
      size of 5 mm to investigate further dose escalation. When delivering the original
      clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration"
      technique yielded the highest tumor control probability (TCP) most frequently,
      followed by the "bone registration" and "tattoo registration" techniques.
      However, the differences in TCP among the three techniques were minor when the
      margin size was 10 mm (?1.1%). Reducing the margin size to 5 mm significantly
      degraded the TCP values of the "tattoo registration" technique in two of the five
      patients, where a large difference was found compared to the other techniques
      (?11.8%). The "CTV registration" technique, however, did maintain similar TCP
      values compared to their 10 mm margin counterpart. In terms of normal tissue
      sparing, the technique producing the lowest NTCP varied from patient to patient.
      Reducing the margin size seemed the only sure way to reduce the NTCP
      significantly, irrespective of the IGART technique employed. In escalating the
      dose with the iso-NTCP constraint, the largest average gain in dose was observed
      with the "tattoo registration" technique, followed by the "CTV registration" and
      "bone registration" techniques. This is attributed to the fact that in three of
      the five patients, the "tattoo registration" technique yielded the lowest NTCP,
      hence a greater window of opportunity to escalate the dose was possible with this
      technique. However, the variation among the five patients was also largest with
      the "tattoo registration" technique where, in the case of one patient, the
      required dose actually needed to be below the original prescription dose of 70 Gy
      to satisfy the iso-NTCP constraint. This was not the case with the "CTV
      registration" technique where positive and similar dose escalation was allowed on
      all five patients. Based on these data, an attractive dose escalation strategy
      may be to implement the "CTV registration" technique (for consistent dosimetric
      coverage) for daily target localization in combination with a margin reduction
      (for increased normal tissue sparing).

PMID- 28493588
TI  - Ion recombination correction for very high dose-per-pulse high-energy electron
      beams.
AB  - The parallel-plate ionization chamber is the recommended tool for the absorbed
      dose measurement in pulsed high-energy electron beams. Typically, the electron
      beams used in radiotherapy have a dose-per-pulse value less then 0.1cGy/pulse. In
      this range the factor to correct the response of an ionization chamber for the
      lack of complete charge collection due to ion recombination (ksat) can be
      properly evaluated with the standard "two voltage" method proposed by the
      international dosimetric reports. Very high dose-per-pulse electron beams are
      employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy
      (IORT). The high dose-per-pulse values (3-13cGy/pulse) characterizing the IORT
      electron beams allow to deliver the therapeutic dose (10-20Gy) in less than a
      minute. This considerably reduces the IORT procedure time, but some dosimetric
      problems arise because the standard method to evaluate ksat overestimates its
      value by 20%. Moreover, if the dose-per-pulse value >1cGy/pulse, the dependence
      of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry.
      In this work the dependence of ksat on the dose-per-pulse value is derived, based
      on the general equation that describes the ion recombination in the Boag theory.
      A new equation for ksat, depending on known or measurable quantities, is
      presented. The new ksat equation is experimentally tested by comparing the
      absorbed doses to water measured with parallel-plate ionization chambers (Roos
      and Markus) to that measured using dose-per-pulse independent dosimeters, such as
      radiochromic films and chemical Fricke dosimeters. These measurements are
      performed in the high dose-per-pulse (3-13cGy/pulse) electron beams of the IORT
      dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements
      made using the parallel-plate chambers and those made using the dose-per-pulse
      independent dosimeters are in good agreement (<3%). This demonstrates the
      possibility of using the parallel-plate ionization chambers also for the very
      high dose-per-pulse (>1cGy/pulse) electron-beam dosimetry.

PMID- 28493589
TI  - Over the next decade the success of radiation treatment planning will be judged
      by the immediate biological response of tumor cells rather than by surrogate
      measures such as dose maximization and uniformity.

PMID- 28493590
TI  - Brain SPECT with short focal-length cone-beam collimation.
AB  - Single-photon emission-computed tomography (SPECT) imaging of deep brain
      structures is compromised by loss of photons due to attenuation. We have
      previously shown that a centrally peaked collimator sensitivity function can
      compensate for this phenomenon, increasing sensitivity over most of the brain.
      For dual-head instruments, parallel-hole collimators cannot provide variable
      sensitivity without simultaneously degrading spatial resolution near the center
      of the brain; this suggests the use of converging collimators. We have designed
      collimator pairs for dual-head SPECT systems to increase sensitivity,
      particularly in the center of the brain, and compared the new collimation
      approach to existing approaches on the basis of performance in estimating
      activity concentration of small structures at various locations in the brain. The
      collimator pairs we evaluated included a cone-beam collimator, for increased
      sensitivity, and a fan-beam collimator, for data sufficiency. We calculated
      projections of an ellipsoidal uniform background, with 0.9-cm-radius spherical
      lesions at several locations in the background. From these, we determined ideal
      signal-to-noise ratios (SNRCRB) for estimation of activity concentration within
      the spheres, based on the Cramer-Rao lower bound on variance. We also
      reconstructed, by an ordered-subset expectation-maximization (OS-EM) procedure,
      images of this phantom, as well as of the Zubal brain phantom, to allow visual
      assessment and to ensure that they were free of artifacts. The best of the
      collimator pairs evaluated comprised a cone-beam collimator with 20 cm focal
      length, for which the focal point is inside the brain, and a fan-beam collimator
      with 40 cm focal length. This pair yielded increased SNRCRB, compared to the
      parallel-parallel pair, throughout the imaging volume. The factor by which SNRCRB
      increased ranged from 1.1 at the most axially extreme location to 3.5 at the
      center. The gains in SNRCRB were relatively robust to mismatches between the
      center of the brain and the center of the imaging volume. Artifact-free
      reconstructions of simulated data acquired using this pair were obtained.
      Combining fan-beam and short-focusing cone-beam collimation should greatly
      improve dual-head brain SPECT imaging, especially for centrally located
      structures.

PMID- 28493591
TI  - Transcatheter interventions in adults with congenital heart disease: Surveys from
      the Society for Cardiovascular Angiography and Interventions to identify current
      patterns of care and perception on training requirements.
AB  - BACKGROUND: Interventional catheterization is central to the care of Adults with
      Congenital Heart Disease (ACHD). Current standards for care provision and
      training in ACHD intervention are lacking. We sought to examine trends in current
      practice and training among interventionalists. METHODS: We analyzed the results
      of two separate international surveys in June 2016. One was sent to all active
      members from the Society of Cardiovascular Angiography and Interventions (SCAI)
      who self-identified Structural Heart Disease or Congenital Heart Disease as a
      practice area. The second survey was conducted through the Pediatric
      Interventional Early Career Society (PICES) aimed at pediatric and adult
      congenital interventionalists in their first seven years after training. The
      total survey sample sizes were 1,535 and 112, respectively. RESULTS: Response
      rates for the SCAI and PICES surveys were 15% (237/1,535) and 75% (84/112),
      respectively. Most respondents (74%) worked at institutions with pediatric and
      adult facilities in proximity (major medical centers). While 75% of SCAI
      respondents believed complex transcatheter procedures should be performed by ACHD
      trained interventionalists or multidisciplinary teams, only 32% reported such
      care is being provided at the present time. Most pediatric and adult
      cardiologists surveyed (73%) do not believe current interventional fellowships
      provide adequate training for proficiency in ACHD interventions. CONCLUSIONS:
      ACHD management remains underdeveloped in relative terms, particularly in the
      United States. Significant gaps in interventional standards of practice and
      future training needs were recognized by this study. Our survey should serve as
      an impetus to establish training guidelines for physicians who seek to perform
      ACHD interventions.

PMID- 28493592
TI  - Experiences of outcome monitoring in service users with psychosis: Findings from
      an Improving Access to Psychological Therapies for people with Severe Mental
      Illness (IAPT-SMI) demonstration site.
AB  - OBJECTIVES: Psychological therapy services are increasingly required to instate
      routine outcome monitoring (ROM), to demonstrate the clinical and economic impact
      of interventions. Professionals' views of ROM are an acknowledged barrier to
      implementation. Service user perspectives have rarely been examined, but
      acceptability and perceptions of ROM are critical to successful implementation.
      We investigated service users' experiences of ROM in an Improving Access to
      Psychological Therapies for people with Severe Mental Illness psychosis
      demonstration site. DESIGN: ROM comprised a periodic assessment battery completed
      at baseline, mid-therapy, and end-of-therapy and a single measure completed
      session-by-session. Qualitative and quantitative feedback were sought at each
      periodic ROM administration, and, for sessional ROM, at mid-therapy and end-of
      therapy. Demographic and clinical correlates of satisfaction were examined cross
      sectionally at baseline. Consistency of satisfaction over time and associations
      of satisfaction with engagement were examined longitudinally. METHODS: Service
      users rated baseline (n = 281/289), mid-therapy (n = 114/121), end-of-therapy (n
      = 124/154), and session-by-session (mid-therapy n = 63/87 and end-of-therapy n =
      90/123) ROM from 0 ('extremely unhelpful') to 10 ('extremely helpful') and gave
      qualitative feedback. RESULTS: Service users predominantly found ROM helpful
      (score 6-10; 64-72%) or neutral (score 5; 19-29%). Finding ROM less helpful was
      associated with younger age and poorer general outcomes, but not with psychotic
      symptoms or therapy dropout. Emerging qualitative themes included feeling
      understood, valuing opportunities to reflect, expressing feelings, and tracking
      progress towards goals. Shorter batteries would be preferable, particularly for
      younger respondents, and those with poorer outcomes. CONCLUSIONS: ROM is
      acceptable for people with psychosis. Tailoring assessments to specific subgroups
      should be considered. PRACTITIONER POINTS: Routine outcome monitoring for
      psychological therapy is acceptable to people with psychosis. Most respondents
      experienced outcome monitoring as an opportunity to feel understood. Younger
      people and those with poorer functioning and well-being might be at higher risk
      of dissatisfaction. Short assessment batteries and less frequent outcome
      monitoring might be preferable for some service users. Limitations of the study
      Feedback about session-by-session outcome monitoring was not contemporaneous with
      completion and may be subject to memory or other biases. Only two-thirds of
      service users provided feedback about session-by-session ROM (compared to >94%
      for periodic ROM) so findings may not be fully representative. Feedback about
      measures was not provided anonymously, and it is possible that service users were
      reluctant to express criticism about ROM to the assessor.

PMID- 28493593
TI  - Superior parathyroid gland approach to the recurrent laryngeal nerve.
AB  - BACKGROUND: The superior parathyroid gland is known to be almost constant in its
      location under the false thyroid capsule. Could it be a landmark to point to the
      site of incision of the false thyroid capsule and find the plane of the recurrent
      laryngeal nerve (RLN) during thyroidectomy? METHODS: The study included 48
      patients with benign goiter scheduled for hemithyroidectomy or total
      thyroidectomy; there were 16 cases of solitary thyroid nodules, 27 cases of
      multinodular goiter, and 5 cases of toxic goiter. RESULTS: This study included 80
      lobectomies. All patients showed no evidence of postoperative RLN palsy,
      bleeding, or hypoparathyroidism. The superior parathyroid gland was consistently
      found within the false capsule in all cases, whereas the inferior parathyroid was
      found within the same layer in 64 sides (80%). CONCLUSION: The described approach
      can accurately guide dissection between true and false capsules of the thyroid to
      reach and preserve both the RLN and the superior parathyroid gland. (c) 2017
      Wiley Periodicals, Inc. Head Neck 39: 1287-1290, 2017.

PMID- 28493594
TI  - Catalytic Asymmetric [3+1]-Cycloaddition Reaction of Ylides with Electrophilic
      Metallo-enolcarbene Intermediates.
AB  - The first asymmetric [3+1]-cycloaddition was successfully achieved by copper(I)
      triflate/double-sidearmed bisoxazoline complex catalyzed reactions of beta
      triisopropylsilyl-substituted enoldiazo compounds with sulfur ylides. This
      methodology delivered a series of chiral cyclobutenes in good yields with high
      enantio- and diastereoselectivities (up to 99 % ee, and >20:1 d.r.).
      Additionally, the [3+1]-cycloaddition of catalytically generated metallo
      enolcarbenes was successfully extended to reaction with a stable benzylidene
      dichlororuthenium complex.

PMID- 28493596
TI  - Overcoming the Tower of Babel in Medical Science by Finding the "EQUATOR":
      Research Reporting Guidelines.

PMID- 28493595
TI  - Empathy in paediatric intensive care nurses part 1: Behavioural and psychological
      correlates.
AB  - AIM: To determine if differences exist between paediatric intensive care nurses
      and allied health professionals in empathy, secondary trauma, burnout, pain
      exposure and pain ratings of self and others. Early and late career differences
      were also examined. BACKGROUND: Nurses are routinely exposed to patient pain
      expression. This work context may make them vulnerable to adverse outcomes such
      as desensitization to patient pain or a compromise in personal well-being.
      DESIGN: Cross-sectional study. METHODS: Data were collected from a convenience
      sample of paediatric intensive care nurses (n = 27) and allied health
      professionals (n = 24), from September 2014-June 2015, at a Canadian health
      centre. Both groups completed one demographic and three behavioural scales.
      Participants underwent fMRI while rating the pain of infant and adult patients in
      a series of video clips. Data were analyzed using parametric and non-parametric
      methods. fMRI results are reported in a second paper. RESULTS: Nurses were
      significantly more likely to be exposed to pain at work than allied health
      professionals and scored significantly higher on dimensions of empathy, secondary
      trauma and burnout. Nurses scored their own pain and the pain of infant and adult
      patients, higher than allied health participants. Less experienced nurses had
      higher secondary trauma and burnout scores than more experienced nurses.
      CONCLUSIONS: Paediatric intensive care work demands, such as patient pain
      exposure, may be associated with nurse's higher report of empathy and pain in
      self and others, but also with higher levels of secondary trauma and burnout,
      when compared with allied health professionals.

PMID- 28493597
TI  - R-warfarin anticoagulant effect.

PMID- 28493598
TI  - Bystander Cardiopulmonary Resuscitation Is Clustered and Associated With
      Neighborhood Socioeconomic Characteristics: A Geospatial Analysis of Kent County,
      Michigan.
AB  - OBJECTIVES: Geographic clustering of bystander cardiopulmonary resuscitation
      (CPR) is associated with demographic and socioeconomic features of the community
      where out-of-hospital cardiac arrest (OHCA) occurred, although this association
      remains largely untested in rural areas. With a significant rural component and
      relative racial homogeneity, Kent County, Michigan, provides a unique setting to
      externally validate or identify new community features associated with bystander
      CPR. Using a large, countywide data set, we tested for geographic clustering of
      bystander CPR and its associations with community socioeconomic features.
      METHODS: Secondary analysis of adult OHCA subjects (2010-2015) in the Cardiac
      Arrest Registry to Enhance Survival (CARES) data set for Kent County, Michigan.
      After linking geocoded OHCA cases to U.S. census data, we used Moran's I-test to
      assess for spatial autocorrelation of population-weighted cardiac arrest rate by
      census block group. Getis-Ord Gi statistic assessed for spatial clustering of
      bystander CPR and mixed-effects hierarchical logistic regression estimated
      adjusted associations between community features and bystander CPR. RESULTS: Of
      1,592 subjects, 1,465 met inclusion criteria. Geospatial analysis revealed
      significant clustering of OHCA in more populated/urban areas. Conversely,
      bystander CPR was less likely in these areas (99% confidence) and more likely in
      suburban and rural areas (99% confidence). Adjusting for clinical, demographic,
      and socioeconomic covariates, bystander CPR was associated with public location
      (odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.03-1.39), initially
      shockable rhythms (OR = 1.48; 95% CI = 1.12-1.96), and those in urban
      neighborhoods (OR = 0.54; 95% CI = 0.38-0.77). CONCLUSIONS: Out-of-hospital
      cardiac arrest and bystander CPR are geographically clustered in Kent County,
      Michigan, but bystander CPR is inversely associated with urban designation. These
      results offer new insight into bystander CPR patterns in mixed urban and rural
      regions and afford the opportunity for targeted community CPR education in areas
      of low bystander CPR prevalence.

PMID- 28493600
TI  - Endurance training selectively increases high-density lipoprotein-bound
      sphingosine-1-phosphate in the plasma.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in
      relatively high concentration in human plasma. Erythrocytes, endothelial cells,
      and activated platelets are the main sources of circulating S1P. The majority of
      plasma S1P is transported bound to high-density lipoprotein (HDL) and albumin. In
      recent years, HDL-bound S1P attracted much attention due to its cardioprotective
      and anti-atherogenic properties. We have previously found that endurance-trained
      athletes are characterized by higher plasma S1P concentration compared to
      untrained individuals. This finding prompted us to examine the effect of
      endurance training on S1P metabolism in blood. Thirteen healthy, untrained, male
      subjects completed an 8-week training program on a rowing ergometer. Three days
      before the first, and 3 days after the last training session, blood samples were
      drawn from an antecubital vein. We found that total plasma S1P concentration was
      increased after the training. Further analysis of different plasma fractions
      showed that the training selectively elevated HDL-bound S1P. This effect was
      associated with activation of sphingosine kinase in erythrocytes and platelets
      and enhanced S1P release from red blood cells. We postulate that increase in HDL
      bound S1P level is one of the mechanisms underlying beneficial effects of regular
      physical activity on cardiovascular diseases.

PMID- 28493599
TI  - Spinal Cord Stimulator Implant Infection Rates and Risk Factors: A Multicenter
      Retrospective Study.
AB  - OBJECTIVES: Spinal cord stimulation is an evidence-based treatment for a number
      of chronic pain conditions. While this therapy offers improvement in pain and
      function it is not without potential complications. These complications include
      device failure, migration, loss of therapeutic paresthesia, and infection. This
      article looked to establish a modern infection rate for spinal cord stimulators,
      assess the impact of known risk factors for surgical site infections and to
      determine the impact of certain preventative measures on the rate of infection.
      METHODS: After institutional review board approval, a multisite, retrospective
      review was conducted on 2737 unique implants or revisions of SCS systems. Patient
      demographics, risk factors including diabetes, tobacco use, obesity, revision
      surgery, trial length, implant location, implant type, surgeon background,
      prophylactic antibiotic use, utilization of a occlusive dressing, and post
      operative antibiotic use were recorded and analyzed. RESULTS: The overall
      infection rate was 2.45% (n = 67). Diabetes, tobacco use, and obesity did not
      independently increase the rate of infection. Revision surgeries had a trend
      toward higher infection rate; however, this did not meet statistical
      significance. There was no difference in the rate of infection between implants
      performed by physicians of different base specialties, cylinder leads vs. paddle
      leads, or between different prophylactic antibiotics. Implants performed at
      academic centers had a higher rate of infection when compared to implants
      performed in nonacademic settings. When patients received an occlusive dressing
      or post-operative antibiotics they had a lower rate of infection. CONCLUSIONS:
      The infection rate (2.45%) reported in this study is lower than the previously
      reported rates (3-6%) and are on par with other surgical specialties. This study
      did not show an increased rate of infection for patients that used tobacco, had
      diabetes or were obese. It's possible that given the low overall infection rate a
      larger study is needed to establish the true impact of these factors on
      infection. In addition, this study did not address the impact of poorly
      controlled diabetes mellitus (elevated hemoglobin A1c) vs. well-controlled
      diabetes. It can be concluded from this study that utilizing an occlusive
      dressing over the incision in the post-operative period decreases the rate of
      infection and should become the standard of care. This study also demonstrated
      the positive impact of post-operative antibiotics in decreasing the rate of
      infection. Studies in other surgical specialties have not shown this impact which
      would suggest that further research is needed.

PMID- 28493601
TI  - Accommodating interruptions: A grounded theory of young people with asthma.
AB  - AIMS AND OBJECTIVES: The aim of this study was to develop an explanatory theory
      on the lives of young people with asthma, issues affecting them and the impact of
      asthma on their day-to-day lives. BACKGROUND: Accommodating Interruptions is a
      theory that explains young people's concerns about living with asthma. Although
      national and international asthma management guidelines exist, it is accepted
      that the symptom control of asthma among the young people population is poor.
      DESIGN: This study was undertaken using Classic Grounded Theory. METHODS: Data
      were collected through in-depth interviews and clinic consultations with young
      people aged 11-16 years who had asthma for over 1 year. Data were also collected
      from participant diaries. Constant comparative analysis, theoretical coding and
      memo writing were used to develop the substantive theory. RESULTS: The theory
      explains how young people resolve their main concern of being restricted by
      Accommodating Interruptions in their lives. They do this by assimilating
      behaviours in balance finding, moderating influence, fitting in and assuming
      control minimising the effects of asthma on their everyday lives. CONCLUSION: The
      theory of Accommodating Interruptions explains young people's asthma management
      behaviours in a new way. It allows us to understand how and why young people
      behave the way they do because they want to participate and be included in
      everyday activities, events and relationships. The theory adds to the body of
      knowledge on how young people with asthma live their day-to-day lives and it
      challenges some existing viewpoints in the literature regarding their behaviours.
      RELEVANCE TO CLINICAL PRACTICE: The findings have implications for developing
      services to support young people in a more meaningful way as they accommodate the
      interruptions associated with asthma in their lives.

PMID- 28493602
TI  - Avenacosides: Metabolism, and potential use as exposure biomarkers of oat intake.
AB  - SCOPE: Exposure biomarkers used for objective estimation of whole-grain (WG)
      intake are essential for epidemiologic studies of WG consumption, however, up to
      now, no exposure biomarkers were developed for WG oat intake. This study
      investigates the potential of oat unique components, Avenacoside-B (AVE-B) and -A
      (AVE-A), as exposure biomarkers of oat intake. METHODS AND RESULTS: An in vivo
      study performed in mice and an in vitro batch fecal fermentation study were used
      to investigate the potential metabolic routes of AVE-B and -A. Twelve healthy
      volunteers were recruited in the human urinary pharmacokinetic study, each
      participant received a single dose of oat bran as breakfast, 48 h urine samples
      were collected at baseline and after treatment period, and AVE-B and -A were
      quantified by LC-MS/MS. Deglycosylation metabolic route was identified as the
      major metabolic path for AVE-B and -A. Urinary AVE-B and -A concentrations
      increased rapidly after oat ingestion, reached their maximum excretion rates
      (ERmax ) fairly simultaneously within 5 h, then decreased gradually. And the mean
      eliminate half-lives (T1/2 ) for AVE-B and -A were determined as 6.22 and 4.55 h,
      respectively. CONCLUSION: Oat AVE-B and -A have great potential to be used as
      specific exposure biomarkers to reflect oat intake.

PMID- 28493603
TI  - Age-related endothelial dysfunction in human skeletal muscle feed arteries: the
      role of free radicals derived from mitochondria in the vasculature.
AB  - AIM: This study sought to determine the role of free radicals derived from
      mitochondria in the vasculature in the recognized age-related endothelial
      dysfunction of human skeletal muscle feed arteries (SMFAs). METHODS: A total of
      44 SMFAs were studied with and without acute exposure to the mitochondria
      targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative
      abundance of proteins from the electron transport chain, phosphorylated (p-) to
      endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD) and the
      mitochondria-derived superoxide (O2-) levels were assessed in SMFA. Endothelium
      dependent and endothelium-independent SMFA vasodilation was assessed in response
      to flow-induced shear stress, acetylcholine (ACh) and sodium nitroprusside (SNP).
      RESULTS: MitoQ restored endothelium-dependent vasodilation in the old to that of
      the young when stimulated by both flow (young: 68 +/- 5; old: 25 +/- 7; old +
      MitoQ 65 +/- 9%) and ACh (young: 97 +/- 4; old: 59 +/- 10; old + MitoQ: 98 +/-
      5%), but did not alter the initially uncompromised, endothelium-independent
      vasodilation (SNP). Compared to the young, MitoQ in the old diminished the
      initially elevated mitochondria-derived O2- levels and appeared to attenuate the
      breakdown of MnSOD. Furthermore, MitoQ increased the ratio of p-eNOS to NOS and
      the restoration of endothelium-dependent vasodilation in the old by MitoQ was
      ablated by NOS blockade. CONCLUSION: This study demonstrated that MitoQ reverses
      age-related vascular dysfunction by what appears to be an NO-dependent mechanism
      in human SMFAs. These findings suggest that mitochondria-targeted antioxidants
      may have utility in terms of counteracting the attenuated blood flow and vascular
      dysfunction associated with advancing age.

PMID- 28493604
TI  - CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4
      sarcomas: a clinicopathological and molecular study.
AB  - AIMS: Approximately 60-70% of high-grade round-cell sarcomas that lack the Ewing
      sarcoma breakpoint region 1 (EWSR1) rearrangement harbour a rearrangement of the
      CIC gene, most commonly CIC-DUX4. Recent studies have established that CIC
      rearranged sarcomas constitute a distinct group characterized by recognizable
      histology and immunoprofiles, such as positivity for ETV4 and WT1 and negativity
      for NKX2.2. Although these sarcomas are diagnosed increasingly in practice by
      fluorescence in-situ hybridization (FISH) with CIC break-apart probes, the
      optimal modality to diagnose these sarcomas has not been determined. In this
      study, we describe four round-cell sarcomas that showed false-negative results by
      CIC break-apart FISH assays. METHODS AND RESULTS: These sarcomas showed
      characteristic histology of CIC-rearranged sarcomas, and all were
      immunohistochemically positive for ETV4 and WT1 and negative for NKX2.2. Although
      FISH showed non-atypical negative signals for CIC rearrangement, high-throughput
      RNA sequencing identified CIC-DUX4 and its fusion breakpoint in all cases. Their
      clinical and histological findings, as well as fusion points determined by RNA
      sequencing, did not differ significantly from those of nine FISH-positive CIC
      DUX4 sarcoma cases. We estimated that the FISH false-negative rate for CIC
      rearranged sarcomas was 14%. Although neither histology nor immunoprofiles (e.g.
      ETV4 and WT1) are entirely sensitive or specific for CIC-rearranged sarcomas, the
      observation that these four cases were identified successfully by such phenotypes
      suggested their practical utility. CONCLUSIONS: CIC break-apart FISH assays
      missed a significant minority of CIC-DUX4 sarcomas, and full awareness of typical
      morphology and judicious immunohistochemical work-ups, including analyses of ETV4
      and WT1, should complement diagnostic assessment.

PMID- 28493606
TI  - MicroRNAs as potential biomarkers to predict the risk of urinary retention
      following intradetrusor onabotulinumtoxin-A injection.
AB  - AIMS: MicroRNAs (miRs) control post-transcriptional gene expression, and this is
      relevant in understanding better chronic diseases and treatment outcomes. The
      role of miRs in the pathology and treatment outcomes of overactive bladder (OAB)
      is unknown. In this study, we assessed the differential expression of miRs in OAB
      patients responding with either normal or elevated post-void residual volumes
      (PVRs) >=200 mL following intradetrusor injection of onabotulinumtoxin-A (onaBoNT
      A). METHODS: Female OAB patients refractory to OAB drugs were consented for this
      study. Cystoscopic-guided punch bladder biopsy was obtained at the time of
      injection of onaBoNT-A 100 units. The expression of 13 miR species, selected for
      their known effect on neurotrophin expression and smooth muscle function, was
      measured. PVRs and urine nerve growth factor (NGF) levels were measured at
      baseline and at the follow-up visit. RESULTS: Fourteen patients with mean age of
      66 years were consented. Of these patients, nine maintained PVRs <200 mL after
      onaBoNT-A injection to comprise the low PVR group. The other five patients with
      PVRs >=200 mL comprised the high PVR group. The expression of miR221 and miR125b
      was upregulated by 11- and 2-fold, respectively, in patients who responded with
      low PVRs after onaBoNT-A (P < 0.05). Urine NGF levels at baseline were not
      different between the two groups. CONCLUSIONS: This study suggests that
      deficiency in the pretreatment expression of miR221 and miR125b may predispose
      OAB patients to high PVRs following intradetrusor onaBoNT-A. Additional studies
      are needed to better understand the role of miRs in OAB.

PMID- 28493605
TI  - Adverse effects of obesity on cognitive functions in individuals at ultra high
      risk for bipolar disorder: Results from the global mood and brain science
      initiative.
AB  - BACKGROUND: The burden of illness associated with bipolar disorder (BD) warrants
      early pre-emption/prevention. Prediction models limited to psychiatric
      phenomenology have insufficient predictive power. Herein, we aimed to evaluate
      whether the presence of overweight/obesity is associated with greater cognitive
      decline in individuals at high risk (HR) or ultra high risk (UHR) for BD.
      METHODS: We conducted a retrospective analysis to investigate the moderational
      role of body mass index (BMI) on measures of cognitive function. Subjects between
      the ages of 8 and 28 years with a positive family history of BD were compared to
      age-matched controls with a negative family history of BD. Subjects with at least
      one biological parent with bipolar I/II disorder were further stratified into UHR
      or HR status by the presence or absence, respectively, of subthreshold hypomanic,
      major depressive, attenuated psychotic, and/or attention-deficit/hyperactivity
      disorder symptoms. RESULTS: A total of 36 individuals at HR for BD, 33
      individuals at UHR for BD, and 48 age-matched controls were included in the
      analysis. Higher BMI was significantly associated with lower performance on
      measures of processing speed (i.e. Brief Assessment of Cognition in Schizophrenia
      symbol coding: r=-.186, P=.047) and attention/vigilance (i.e. Continuous
      Performance Test-Identical Pairs: r=-.257, P=.006). There were trends for
      negative correlations between BMI and measures of working memory (i.e. Wechsler
      Memory Scale-III Spatial Span: r=-0.177, P=.059) and overall cognitive function
      (i.e. Measurement and Treatment Research to Improve Cognition in Schizophrenia
      composite score: r=-.157, P=.097). Negative associations between BMI and
      cognitive performance were significantly stronger in the UHR group than in the HR
      group, when compared to controls. CONCLUSIONS: Individuals at varying degrees of
      risk for BD exhibit greater cognitive impairment as a function of co-existing
      overweight/obesity. Prediction models for BD may be substantively informed by
      including information related to overweight/obesity and, perhaps, other general
      medical conditions that share pathology with BD. Our findings herein, as well as
      the salutary effects of bariatric surgery on measures of cognitive function in
      obese populations, provide the rationale for hypothesizing that mitigating excess
      weight in individuals at elevated risk for BD may forestall or prevent
      declaration of illness.

PMID- 28493607
TI  - Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted
      Malononitriles.
AB  - beta-Ketonitriles bearing a quaternary carbon at the 2-position were prepared
      through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted
      malononitriles. In contrast to the previously described transnitrilative
      cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction
      avoids retro-Thorpe collapse of the intermediate addition product through the use
      of a milder base. The reaction was amenable to a variety of aryl boronic acids
      and disubstituted malononitriles, providing a diverse array of beta-ketonitriles.
      The products could be further derivatized to valuable chiral alpha,alpha
      disubstituted-beta-aminonitriles through addition reactions to the corresponding
      N-tert-butanesulfinyl imines.

PMID- 28493609
TI  - Second cancer risk assessments after involved-site radiotherapy for mediastinal
      Hodgkin lymphoma.
AB  - PURPOSE: This study was conducted to provide second cancer risk assessments
      attributable to involved-site radiotherapy (ISRT) of mediastinal Hodgkin lymphoma
      (HL) and to compare these risks with those from the conventional involved-field
      radiation therapy (IFRT). METHODS: Both ISRT and IFRT plans were made for 11
      patients (six females, five males) with HL in the region of mediastinum. All
      three-dimensional plans involved 6 MV photon beams and delivered 30 Gy to the
      target site. Differential dose-volume histograms were defined for the lung,
      female breast, and esophagus which were partly included within the planned
      treatment fields. The patient-specific organ equivalent dose (OED) and the
      relevant lifetime attributable risk (LAR) of developing malignancies in each of
      the above critical organs were determined with the aid of a mechanistic, plateau
      and bell-shaped models. The LAR estimates were compared with the baseline risks
      for unexposed people. RESULTS: The OED range of lung, breast, and esophagus
      calculated by the ISRT plans was 176.1-360.2, 19.5-124.1, and 42.6-157.7 cGy,
      respectively. The resultant LARs of developing lung and breast cancer as
      estimated by the three different models were at least 1.8 and 5.3 times lower
      than the baseline risks, respectively. The probability for the appearance of
      radiation-induced esophageal malignancies from ISRT in males was also up to 3.8
      times smaller than the nominal incidence cancer rates. The corresponding
      probability in irradiated females exceeded the baseline risks. The estimated
      lifetime risks for lung and breast cancer induction due to ISRT were
      systematically and significantly lower than those from the IFRT irrespective of
      the model used for analysis (P < 0.05). No significant difference was found
      between the LARs for esophageal cancer development estimated by the ISRT and IFRT
      plans (P = 0.63). CONCLUSIONS: The presented second cancer risk data may be of
      value in the selection of the optimal radiotherapy technique for the management
      of mediastinal HL and in the subsequent follow-up of irradiated patients.

PMID- 28493610
TI  - Fractionated aliphatic alcohols as synthetic precursors of ultra long-chain
      monoacylglycerols for cosmetic applications.
AB  - BACKGROUND: Xerosis is an abnormally dry and flaky skin condition that is
      associated with a change in the packing behaviour of the lipid matrix in the
      stratum corneum (SC), the outermost layer of the skin. This skin condition can
      lead to an increase in transepidermal water loss (TEWL). As ultralong-chain fatty
      acids have a positive effect on maintaining the packing behaviour of the SC lipid
      matrix, a moisturizer which contains glycerides of ultralong-chain fatty acids
      could act as a semi-occlusive layer on the surface of the skin. This will lower
      the rate of water evaporation through the epidermis and consequently help prevent
      or improve skin xerosis. OBJECTIVE: To identify a novel source of ultralong-chain
      lipids and develop monoacylglycerols with mixed fatty acyl chain lengths that
      have occlusive properties superior to petrolatum. METHODS: Initially, Performacol
      425, a mixture of very long-chain fatty alcohols, was fractionated using short
      path distillation to yield a fraction enriched with C22:0-C26:0 fatty alcohols.
      The fatty alcohol fraction was then oxidized using Jones reagent, and the
      resulting fatty acids were esterified with glycerol to yield the corresponding
      monoglycerides using Novozym 435. These were then evaluated using Fourier
      transform infrared spectroscopy, differential scanning calorimetry and water
      vapour transmission rate measurements. RESULTS: The monoacylglycerols enriched
      with C22:0-C26:0 displayed a melting point of 80 degrees C and orthorhombic
      packing; packing behaviour mainly present in healthy SC. In addition, a
      phospholipid-structured emulsion containing 3% of the monoglycerides displayed
      occlusive properties superior to the vehicle containing 3% petrolatum jelly.
      CONCLUSIONS: Performacol 425 can be a potential source of fatty alcohols to
      synthesize monoacylglycerols that can improve the occlusive behaviour of
      phospholipid-structured emulsions.

PMID- 28493608
TI  - The Epidemiology of Emergency Department Trauma Discharges in the United States.
AB  - OBJECTIVE: Injury-related morbidity and mortality is an important emergency
      medicine and public health challenge in the United States. Here we describe the
      epidemiology of traumatic injury presenting to U.S. emergency departments (EDs),
      define changes in types and causes of injury among the elderly and the young,
      characterize the role of trauma centers and teaching hospitals in providing
      emergency trauma care, and estimate the overall economic burden of treating such
      injuries. METHODS: We conducted a secondary retrospective, repeated cross
      sectional study of the Nationwide Emergency Department Data Sample (NEDS), the
      largest all-payer ED survey database in the United States. Main outcomes and
      measures were survey-adjusted counts, proportions, means, and rates with
      associated standard errors (SEs) and 95% confidence intervals. We plotted annual
      age-stratified ED discharge rates for traumatic injury and present tables of
      proportions of common injuries and external causes. We modeled the association of
      Level I or II trauma center care with injury fatality using a multivariable
      survey-adjusted logistic regression analysis that controlled for age, sex, injury
      severity, comorbid diagnoses, and teaching hospital status. RESULTS: There were
      181,194,431 (SE = 4,234) traumatic injury discharges from U.S. EDs between 2006
      and 2012. There was a mean year-to-year decrease of 143 (95% CI = -184.3 to 
      68.5) visits per 100,000 U.S. population during the study period. The all-age,
      all-cause case-fatality rate for traumatic injuries across U.S. EDs during the
      study period was 0.17% (SE = 0.001%). The case-fatality rate for the most
      severely injured averaged 4.8% (SE = 0.001%), and severely injured patients were
      nearly four times as likely to be seen in Level I or II trauma centers (relative
      risk = 3.9 [95% CI = 3.7 to 4.1]). The unadjusted risk ratio, based on group
      counts, for the association of Level I or II trauma centers with mortality was
      risk ratio = 4.9 (95% CI = 4.5 to 5.3); however, after sex, age, injury severity,
      and comorbidities were accounted for, Level I or II trauma centers were not
      associated with an increased risk of fatality (odds ratio = 0.96 [95% CI = 0.79
      to 1.18]). There were notable changes at the extremes of age in types and causes
      of ED discharges for traumatic injury between 2009 and 2012. Age-stratified rates
      of diagnoses of traumatic brain injury increased 29.5% (SE = 2.6%) for adults
      older than 85 and increased 44.9% (SE = 1.3%) for children younger than 18.
      Firearm-related injuries increased 31.7% (SE = 0.2%) in children 5 years and
      younger. The total inflation-adjusted cost of ED injury care in the United States
      between 2006 and 2012 was $99.75 billion (SE = $0.03 billion). CONCLUSIONS:
      Emergency departments are a sensitive barometer of the continuing impact of
      traumatic injury as an important cause of morbidity and mortality in the United
      States. Level I or II trauma centers remain a bulwark against the tide of severe
      trauma in the United States, but the types and causes of traumatic injury in the
      United States are changing in consequential ways, particularly at the extremes of
      age, with traumatic brain injuries and firearm-related trauma presenting
      increased challenges.

PMID- 28493611
TI  - Fucoidan ameliorates pancreatic beta-cell death and impaired insulin synthesis in
      streptozotocin-treated beta cells and mice via a Sirt-1-dependent manner.
AB  - SCOPE: Several beneficial biological functions of fucoidan (FO) isolated from
      brown algae have been demonstrated. The purpose of this study was to investigate
      whether FO derived from Sargassum hemiphyllum ameliorates pancreatic beta-cell
      damage and impaired insulin synthesis under diabetic condition. METHODS AND
      RESULTS: The effects of FO were studied in streptozotocin (STZ)-treated
      pancreatic beta-cell line, NIT-1cells, and mice. The cell apoptosis, protein
      analyses, histological examination, and pancreatic function assays were
      performed. The increased pancreatic beta-cell apoptosis and decreased insulin
      secretion observed in STZ-treated NIT-1 cells and mice were greatly attenuated by
      FO. Moreover, FO has an ability to enhance glucagon-like peptide-1 receptor (GLP
      1R) and sirtuin 1 (Sirt-1) activity through activation of AMPK/GAPDH/PDX-1
      cascade in STZ-treated beta cells. However, the effects of FO were significantly
      reversed by EX527, a specific Sirt-1 inhibitor. Similarly, the hyperglycemia,
      lower expression of Sirt-1, PDX-1, and GLP-1R in the pancreas of diabetic mice
      were markedly improved after FO administration. CONCLUSION: We demonstrated that
      FO exhibits an anti-diabetic effect mainly through attenuation of beta-cell
      death, thereby elevating insulin synthesis by upregulating PDX-1 and GLP1-R via a
      Sirt-1-dependent manner. Therefore, FO-containing food or supplements may have a
      therapeutic effect for diabetes by preventing beta-cell damage and dysfunction.

PMID- 28493612
TI  - Identification of extracellular matrix protein 1 as a potential plasma biomarker
      of ESCC by proteomic analysis using iTRAQ and 2D-LC-MS/MS.
AB  - PURPOSE: This study was aimed to conduct a proteomics profiling analysis on
      plasma obtained from ESCC patients with the goal of identifying appropriate
      plasma protein biomarkers in the progression of ESCC. EXPERIMENTAL DESIGN: Plasma
      from 28 ESCC patients and 28 healthy controls (HC) were analyzed by iTRAQ
      combined with 2D-LC-MS/MS. ProteinPilot software was used to identify the
      differentially expressed plasma proteins in ESCC compared to HC. Western blot was
      performed to verify the expression of selected proteins in 37 independent ESCC
      patients and 37 HC. Transwell and MTT assays were used to detect the biological
      function of ECM1 protein in vitro. RESULTS: Nineteen (four upregulated and
      fifteen downregulated) proteins were identified as differentially expressed
      between ESCC and HC (p <0.05). Biological functions of these proteins are
      involved in cell adhesion, cell apoptosis and metabolic processes, visual
      perception and immune response. Of these, extracellular matrix 1 (ECM1) and
      lumican (LUM) were selected further confirmation by Western blot (p <0.05), which
      were consistent with the iTRAQ results. Furthermore, the migration ability of
      EC9706 cell line after overexpressing ECM1 was increased significantly (p <0.05).
      The proliferation ability of HUVEC cell was enhanced when treated with the
      culture supernatants of EC9706 overexpressed ECM1(p <0.05). CONCLUSION AND
      CLINICAL RELEVANCE: This proteome analysis indicate that ECM1 is a potential
      novel plasma protein biomarker for the detection of primary ESCC and evaluation
      of neoplasms progression.

PMID- 28493613
TI  - Subtle blood-brain barrier leakage rate and spatial extent: Considerations for
      dynamic contrast-enhanced MRI.
AB  - PURPOSE: Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain
      barrier (BBB) leakage. In neurodegenerative disorders such as small vessel
      disease and dementia, the leakage can be very subtle and the corresponding signal
      can be rather noisy. For these reasons, an optimized DCE-MRI measurement and
      study design is required. To this end, a new measure indicative of the spatial
      extent of leakage is introduced and the effects of scan time and sample size are
      explored. METHODS: Dual-time resolution DCE-MRI was performed in 16 patients with
      early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (Ki )
      and volume fraction of detectable leaking tissue (vL ) to quantify the spatial
      extent of BBB leakage were calculated in cortical gray matter and white matter
      using noise-corrected histogram analysis of leakage maps. Computer simulations
      utilizing realistic Ki histograms, mimicking the strong effect of noise and
      variation in Ki values, were performed to understand the influence of scan time
      on the estimated leakage. RESULTS: The mean Ki was very low (order of 10-4 min-1
      ) and highly influenced by noise, causing the Ki to be increasingly overestimated
      at shorter scan times. In the white matter, the Ki was not different between
      patients with early AD and controls, but was higher in the cortex for patients,
      reaching significance after 14.5 min of scan time. To detect group differences,
      vL proved more suitable, showing significantly higher values for patients
      compared with controls in the cortex after 8 minutes of scan time, and in white
      matter after 15.5 min. CONCLUSIONS: Several ways to improve the sensitivity of a
      DCE-MRI experiment to subtle BBB leakage were presented. We have provided vL as
      an attractive and potentially more time-efficient alternative to detect group
      differences in subtle and widespread blood-brain barrier leakage compared with
      leakage rate Ki . Recommendations on group size and scan time are made based on
      statistical power calculations to aid future research.

PMID- 28493614
TI  - Accuracy of Physical Examination, Ankle-Brachial Index, and Ultrasonography in
      the Diagnosis of Arterial Injury in Patients With Penetrating Extremity Trauma: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Penetrating Extremity Trauma (PET) may result in arterial injury, a
      rare but limb- and life-threatening surgical emergency. Timely, accurate
      diagnosis is essential for potential intervention in order to prevent significant
      morbidity. OBJECTIVES: Using a systematic review/meta-analytic approach, we
      determined the utility of physical examination, Ankle-Brachial Index (ABI), and
      Ultrasonography (US) in the diagnosis of arterial injury in emergency department
      (ED) patients who have sustained PET. We applied a test-treatment threshold model
      to determine which evaluations may obviate CT Angiography (CTA). METHODS: We
      searched PubMed, Embase, and Scopus from inception to November 2016 for studies
      of ED patients with PET. We included studies on adult and pediatric subjects. We
      defined the reference standard to include CTA, catheter angiography, or surgical
      exploration. When low-risk patients did not undergo the reference standard,
      trials must have specified that patients were observed for at least 24 hours. We
      used the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) to
      evaluate bias and applicability of the included studies. We calculated positive
      and negative likelihood ratios (LR+ and LR-) of physical examination ("hard
      signs" of vascular injury), US, and ABI. Using established CTA test
      characteristics (sensitivity = 96.2%, specificity = 99.2%) and applying the
      Pauker-Kassirer method, we developed a test-treatment threshold model (testing
      threshold = 0.14%, treatment threshold = 72.9%). RESULTS: We included eight
      studies (n = 2,161, arterial injury prevalence = 15.5%). Studies had variable
      quality with most at high risk for partial and double verification bias. Some
      studies investigated multiple index tests: physical examination (hard signs) in
      three studies (n = 1,170), ABI in five studies (n = 1,040), and US in four
      studies (n = 173). Due to high heterogeneity (I2  > 75%) of the results, we could
      not calculate LR+ or LR- for hard signs or LR+ for ABI. The weighted prevalence
      of arterial injury for ABI was 14.3% and LR- was 0.59 (95% confidence interval
      [CI] = 0.48-0.71) resulting in a posttest probability of 9% for arterial injury.
      Ultrasonography had weighted prevalence of 18.9%, LR+ of 35.4 (95% CI = 8.3-151),
      and LR- of 0.24 (95% CI = 0.08-0.72); posttest probabilities for arterial injury
      were 89% and 5% after positive or negative US, respectively. The posttest
      probability of arterial injury with positive US (89%) exceeded the CTA treatment
      threshold (72.9%). The posttest probabilities of arterial injury with negative US
      (5%) and normal ABI (9%) exceeded the CTA testing threshold (0.14%). Normal
      examination (no hard or soft signs) with normal ABI in combination had LR- of
      0.01 (95% CI = 0.0-0.10) resulting in an arterial injury posttest probability of
      0%. CONCLUSIONS: In PET patients, positive US may obviate CTA. In patients with a
      normal examination (no hard or soft signs) and a normal ABI, arterial injury can
      be ruled out. However, a normal ABI or negative US cannot independently exclude
      arterial injury. Due to high study heterogeneity, we cannot make recommendations
      when hard signs are present or absent or when ABI is abnormal. In these
      situations, one should use clinical judgment to determine the need for further
      observation, CTA or catheter angiography, or surgical exploration.

PMID- 28493615
TI  - Why we need fairer allocation rules for patients with hepatocellular carcinoma
      awaiting a liver transplant?

PMID- 28493616
TI  - Impact of a webcast on nurses' delivery of tobacco dependence treatment.
AB  - AIMS AND OBJECTIVES: To evaluate an educational programme about nurses' role in
      tobacco dependence treatment, and its webcast component, on the long-term impact
      of increasing the frequency of nurses' self-reported changes in practice related
      to delivery of smoking cessation interventions. BACKGROUND: Healthcare
      professionals' knowledge about evidence-based tobacco dependence treatment using
      the 5As framework (Ask about tobacco use, Advise users to quit, Assess
      willingness to quit, Assist in making a quit plan and Arrange for follow-up,
      including referral to a quitline) is essential to increase smoking cessation
      rates in the United States. DESIGN: A 6-month pre-post design. METHODS: A
      convenience sample of nurses (N = 283) from Kentucky and Louisiana was provided
      access to the webcast and printed toolkit. Responses from those who completed an
      online survey at baseline, and at 3 or 6 months postimplementation of the
      educational programme were included in an analysis of changes in the consistent
      (always/usually) delivery of the 5As plus referral to the quitline. RESULTS:
      After 3 months, the intervention had a significant impact on increasing nurses'
      reports of consistently providing the 5As to patients who smoked, which was
      largely sustained at 6 months. Nurses who viewed the webcast were three times
      more likely to refer smokers to a quitline at 3 months; and four times more
      likely at 6 months than those who did not. CONCLUSIONS: An online educational
      programme, plus printed toolkit about tobacco dependence treatment increased
      nurses' delivery of smoking cessation interventions over time. This study
      provided preliminary evidence that including a webcast in a nurse-targeted
      educational programme could significantly increase the proportion of nurses who
      referred smokers to a quitline beyond the benefit of access to printed materials
      and web-based resources. RELEVANCE TO CLINICAL PRACTICE: Distance learning is a
      feasible mechanism for enhancing nurses' involvement in tobacco dependence
      treatment and promoting evidence-based clinical practice.

PMID- 28493617
TI  - Anti-inflammatory bioactive equivalence of combinatorial components beta
      carboline alkaloids identified in Arenaria kansuensis by two-dimensional
      chromatography and solid-phase extraction coupled with liquid-liquid extraction
      enrichment technology.
AB  - Bioactive equivalent combinatorial components play a critical role in herbal
      medicines. However, how to discover and enrich them efficiently is a question for
      herbal pharmaceuticals researchers. In our work, a novel two-dimensional reversed
      phase/hydrophilic interaction high-performance liquid chromatography method was
      established to perform real-time components trapping and combining for
      preparation and isolation of coeluting components. Arenaria kansuensis was taken
      as an example, and solid-phase extraction coupled with liquid-liquid extraction
      as a simple and efficient method for enriching trace components, reversed phase
      column coupled with hydrophilic interaction liquid chromatography XAmide column
      as two-dimensional chromatography technology for isolation and preparation of
      coeluting constituents, enzyme-linked immune-sorbent assay as bio-guided assay,
      and anti-inflammatory bioactivity evaluation for bioactive constituents. A
      combination of 12 beta-carboline alkaloids was identified as anti-inflammatory
      bioactive equivalent combinatorial components from A. kansuensis, which accounts
      for 1.9% w/w of original A. kansuensis. This work answers the key question of
      which are real anti-inflammatory components from A. kansuensis and provides a
      fast and efficient approach for discovering and enriching trace beta-carboline
      alkaloids from herbal medicines for the first time. More importantly, the
      discovery of bioactive equivalent combinatorial components could improve the
      quality control of herbal products and inspire a herbal medicine based on
      combinatorial therapeutics.

PMID- 28493618
TI  - Pondering practice: Enhancing the art of reflection.
AB  - AIMS AND OBJECTIVES: The aim of this study was to describe the effect that
      immersive simulation experiences and guided reflection can have on the
      undergraduate nurses' understanding of how stressful environments impact their
      emotions, performance and ability to implement safe administration of
      medications. BACKGROUND: Patient safety can be jeopardised if nurses are unsure
      of how to appropriately manage and respond to interruptions. Medication
      administration errors are a major patient safety issue and often occur as a
      consequence of ineffective interruption management. The skills associated with
      medication administration are most often taught to, and performed by,
      undergraduate nurses in a controlled environment. However, the clinical
      environment in which nurses are expected to administer medications is often
      highly stressed and nurses are frequently interrupted. DESIGN/METHODS: This study
      used role-play simulation and written reflections to facilitate deeper levels of
      student self-awareness. A qualitative approach was taken to explore students'
      understanding of the effects of interruptions on their ability to undertake safe
      medication administration. Convenience sampling of second-year undergraduate
      nursing students enrolled in a medical-surgical subject was used in this study.
      Data were obtained from 451:528 (85.42%) of those students and analysed using
      thematic analysis. RESULTS: Students reported increasing consciousness and the
      importance of reflection for evaluating performance and gaining self-awareness.
      They described self-awareness, effective communication, compassion and empathy as
      significant factors in facilitating self-efficacy and improved patient care
      outcomes. CONCLUSIONS: Following a role-play simulation experience, student
      nurses reported new knowledge and skill acquisition related to patient safety,
      and new awareness of the need for empathetic and compassionate care during
      medication administration. Practicing medication administration in realistic
      settings adds to current strategies that aim to reduce medication errors by
      allowing students to reflect on and in practice and develop strategies to ensure
      patient safety. RELEVANCE TO CLINICAL PRACTICE: Experiencing clinical scenarios
      within the safety of simulated environments, offers undergraduate student nurses
      an opportunity to reflect on practice to provide safer, more empathetic and
      compassionate care for patients in the future.

PMID- 28493619
TI  - Access to Hexahydrocarbazoles: The Thorpe-Ingold Effects of the Ligand on
      Enantioselectivity.
AB  - A novel cyclization reaction of methylenemalonate with indoles is reported, and
      it provides efficient access to a variety of hexahydrocarbazoles. The
      enantioselective version was realized by a finely tuned ligand/CuII catalyst. The
      optically active hexahydrocarbazoles contain three quaternary carbon centers and
      are obtained in up to 99 % yield with greater than 99:1 d.r. and up to greater
      than 99 % ee. This reaction can be carried out on gram scale and stereoselective
      transformation of the product led to the core structure of a series of alkaloids
      from Kopsia plants.

PMID- 28493621
TI  - Substituent Effects in Parallel-Displaced pi-pi Stacking Interactions: Distance
      Matters.
AB  - Host-guest systems with Rebek imide type receptors and a 2,6
      di(isobutyramido)pyridine ligand were employed to investigate substituent effects
      in parallel-displaced pi-pi stacking interactions. Changing the intermolecular
      distance between the para substituent on the aromatic platform of the receptor
      and the pyridine ring of the guest results in a strongly different substituent
      effect. With a short ethyne-1,2-diyl spacer between the Rebek imide and the
      aromatic platform, partial overlap of substituent and guest stabilizes the pi-pi
      stacking interactions independent of the electronic nature of the substituent
      (Wheeler-Houk model). When the substituent is shifted further away by using a
      buta-1,3-diyne-1,4-diyl spacer, direct, through-space interactions between
      substituent and guest are prevented. A linear correlation between logKa (Ka
      =association constant) and the Hammett substituent constant sigmapara is
      observed, confirming predictions by the Hunter-Sanders model experimentally.

PMID- 28493620
TI  - Engineering a Small HOMO-LUMO Gap and Intramolecular C-H Borylation by
      Diborene/Anthracene Orbital Intercalation.
AB  - The diborene 1 was synthesized by reduction of a mixture of 1,2-di-9-anthryl-1,2
      dibromodiborane(4) (6) and trimethylphosphine with potassium graphite. The X-ray
      structure of 1 shows the two anthryl rings to be parallel and their pi(C14 )
      systems perpendicular to the diborene pi(B=B) system. This twisted conformation
      allows for intercalation of the relatively high-lying pi(B=B) orbital and the low
      lying pi* orbital of the anthryl moiety with no significant conjugation,
      resulting in a small HOMO-LUMO gap (HLG) and ultimately a C-H borylation of the
      anthryl unit. The HLG of 1 was estimated to be 1.57 eV from the onset of the long
      wavelength band in its UV/Vis absorption spectrum (THF, lambdaonset =788 nm). The
      oxidation of 1 with elemental selenium afforded diboraselenirane 8 in
      quantitative yield. By oxidative abstraction of one phosphine ligand by another
      equivalent of elemental selenium, the B-B and C1 -H bonds of 8 were cleaved to
      give the cyclic 1,9-diborylanthracene 9.

PMID- 28493622
TI  - IUAPC 2017 Distinguished Women in Chemistry or Chemical Engineering.

PMID- 28493624
TI  - The effect of acute exercise on blood concentrations of brain-derived
      neurotrophic factor in healthy adults: a meta-analysis.
AB  - It has been hypothesized that one mechanism through which physical activity
      provides benefits to cognition and mood is via increasing brain-derived
      neurotrophic factor (BDNF) concentrations. Some studies have reported immediate
      benefits to mood and various cognitive domains after a single session of
      exercise. This meta-analysis sought to determine the effect of a single exercise
      session on concentrations of BDNF in peripheral blood, in order to evaluate the
      potential role of BDNF in mediating the beneficial effects of exercise on brain
      health. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine
      Source, and CINAHL databases were searched for original, peer-reviewed reports of
      peripheral blood BDNF concentrations before and after acute exercise
      interventions. Risk of bias within studies was assessed using standardized
      criteria. Standardized mean differences (SMDs) were generated from random effects
      models. Risk of publication bias was assessed using a funnel plot and Egger's
      test. Potential sources of heterogeneity were explored in subgroup analyses. In
      55 studies that met inclusion criteria, concentrations of peripheral blood BDNF
      were higher after exercise (SMD = 0.59, 95% CI: 0.46-0.72, P < 0.001). In meta
      regression analysis, greater duration of exercise was associated with greater
      increases in BDNF. Subgroup analyses revealed an effect in males but not in
      females, and a greater BDNF increase in plasma than serum. Acute exercise
      increased BDNF concentrations in the peripheral blood of healthy adults. This
      effect was influenced by exercise duration and may be different across genders.

PMID- 28493625
TI  - Significant OH production under surface cleaning and air cleaning conditions:
      Impact on indoor air quality.
AB  - We report measurements of hydroxyl (OH) and hydroperoxy (HO2 ) radicals made by
      laser-induced fluorescence spectroscopy in a computer classroom (i) in the
      absence of indoor activities (ii) during desk cleaning with a limonene-containing
      cleaner (iii) during operation of a commercially available "air cleaning" device.
      In the unmanipulated environment, the one-minute averaged OH concentration
      remained close to or below the limit of detection (6.5*105  molecule cm-3 ),
      whilst that of HO2 was 1.3*107  molecule cm-3 . These concentrations increased to
      ~4*106 and 4*108  molecule cm-3 , respectively during desk cleaning. During
      operation of the air cleaning device, OH and HO2 concentrations reached ~2*107
      and ~6*108  molecule cm-3 respectively. The potential of these OH concentrations
      to initiate chemical processing is explored using a detailed chemical model for
      indoor air (the INDCM). The model can reproduce the measured OH and HO2
      concentrations to within 50% and often within a few % and demonstrates that the
      resulting secondary chemistry varies with the cleaning activity. Whilst terpene
      reaction products dominate the product composition following surface cleaning,
      those from aromatics and other VOCs are much more important during the use of the
      air cleaning device.

PMID- 28493623
TI  - Aripiprazole Suppression of Drinking in a Clinical Laboratory Paradigm: Influence
      of Impulsivity and Self-Control.
AB  - BACKGROUND: Aspects of impulsivity have been implicated in the development, or
      maintenance, of alcohol use disorder (AUD). The brain dopamine system is
      implicated in both reward processing/memory (typically subcortical) and in brain
      inhibitory control mechanisms (typically cortical). Using a validated clinical
      laboratory paradigm, the dopamine/serotonin "stabilizing" drug, aripiprazole was
      evaluated in non-treatment-seeking AUD individuals based on their level of
      impulsivity/self-control. METHODS: Ninety-nine individuals (77% male; mean age
      27; 7.5 drinks per day; 83% heavy drinking days) meeting DSM-IV criteria for
      alcohol dependence were randomized to aripiprazole (N = 47 evaluable) or placebo
      (N = 48 evaluable) based on their Barratt Impulsiveness Scale (BIS-11) score
      (above or below 68). Aripiprazole, or similar placebo, was titrated to 15 mg over
      8 days. Drinking was recorded over 6 days under natural conditions. On Day 8,
      after 1 day of required abstinence, individuals participated in a bar laboratory
      paradigm that included a priming drink (breath alcohol concentration [BAC] target
      0.02 to 0.03 g/dl) and free-choice consumption of up to 8 drinks (max BAC 0.1
      g/dl) in exchange for a "bar credit" of $2 per drink (max $16). End points were
      drinks per day under natural conditions and drinks consumed in the bar laboratory
      after the priming drink. RESULTS: There was no significant main effect of
      aripiprazole or interaction with BIS-11 score during the natural drinking period.
      However, there was a main effect of aripiprazole on bar laboratory drinking (p =
      0.04) and aripiprazole reduced the total number of drinks consumed more among
      individuals with low self-control (p = 0.034) and increased latency to consume
      those drinks (p = 0.045) more among those with high impulsivity. Relative to
      placebo, aripiprazole caused more side effects and increased alcohol-induced
      sedation, but neither significantly influenced its interaction with
      impulsivity/self-control scores on drinking. CONCLUSIONS: This paradigm forced a
      choice between immediate drinking reward and delayed monetary reward. In those
      with high impulsivity and/or low self-control, aripiprazole shifts the balance
      away from immediate drinking toward a later reward. Medications targeting
      cortical dopamine/serotonin balance might show clinical benefit of reduced
      drinking, among individuals with impulsivity/low self-control.

PMID- 28493626
TI  - Why Do People Choose Emergency and Urgent Care Services? A Rapid Review Utilizing
      a Systematic Literature Search and Narrative Synthesis.
AB  - OBJECTIVES: Rising demand for emergency and urgent care services is well
      documented, as are the consequences, for example, emergency department (ED)
      crowding, increased costs, pressure on services, and waiting times. Multiple
      factors have been suggested to explain why demand is increasing, including an
      aging population, rising number of people with multiple chronic conditions, and
      behavioral changes relating to how people choose to access health services. The
      aim of this systematic mapping review was to bring together published research
      from urgent and emergency care settings to identify drivers that underpin patient
      decisions to access urgent and emergency care. METHODS: Systematic searches were
      conducted across Medline (via Ovid SP), EMBASE (via Ovid), The Cochrane Library
      (via Wiley Online Library), Web of Science (via the Web of Knowledge), and the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL; via EBSCOhost).
      Peer-reviewed studies written in English that reported reasons for accessing or
      choosing emergency or urgent care services and were published between 1995 and
      2016 were included. Data were extracted and reasons for choosing emergency and
      urgent care were identified and mapped. Thematic analysis was used to identify
      themes and findings were reported qualitatively using framework-based narrative
      synthesis. RESULTS: Thirty-eight studies were identified that met the inclusion
      criteria. Most studies were set in the United Kingdom (39.4%) or the United
      States (34.2%) and reported results relating to ED (68.4%). Thirty-nine percent
      of studies utilized qualitative or mixed research designs. Our thematic analysis
      identified six broad themes that summarized reasons why patients chose to access
      ED or urgent care. These were access to and confidence in primary care; perceived
      urgency, anxiety, and the value of reassurance from emergency-based services;
      views of family, friends, or healthcare professionals; convenience (location, not
      having to make appointment, and opening hours); individual patient factors (e.g.,
      cost); and perceived need for emergency medical services or hospital care,
      treatment, or investigations. CONCLUSIONS: We identified six distinct reasons
      explaining why patients choose to access emergency and urgent care services:
      limited access to or confidence in primary care; patient perceived urgency;
      convenience; views of family, friends, or other health professionals; and a
      belief that their condition required the resources and facilities offered by a
      particular healthcare provider. There is a need to examine demand from a whole
      system perspective to gain better understanding of demand for different parts of
      the emergency and urgent care system and the characteristics of patients within
      each sector.

PMID- 28493627
TI  - Oxidative-Insertion Reactivity Across a Geometrically Constrained Metal->Borane
      Interaction.
AB  - While interest in cooperative reactivity of transition metals and Lewis acids is
      receiving significant attention, the scope of known reactions that directly
      exploit the polarized reverse-dative sigma-bond of metal-borane complexes (i.e.,
      M->BR3 ) remains limited. Described herein is that the platinum
      (boryl)iminomethane (BIM) complex [Pt(kappa2 -N,B-Cy2 BIM)(CNArDipp2 )] can
      effect the oxidative insertion of a range of unsaturated organic substrates,
      including azides, isocyantes, and nitriles, as well as CO2 and elemental sulfur
      (S8 ). In addition, alkyl migration processes available to the BIM framework
      allow for post-insertion reaction sequences resulting in product release from the
      metal center.

PMID- 28493628
TI  - The confidence of undergraduate dental students when carrying out prosthodontic
      treatment and their perception of the quality of prosthodontic education.
AB  - INTRODUCTION: Despite the falling number of edentulous patients within the UK,
      there is still a large demand for the provision of removable prostheses. On
      qualification, dentists should have the knowledge and skills to provide these
      prostheses, but previous studies have shown that final-year dental undergraduate
      confidence in treating denture patients is lacking. AIM: To explore undergraduate
      dental student confidence whilst carrying out prosthodontic treatment, and to
      explore their perceptions of the quality of their prosthodontic education.
      METHOD: An anonymous questionnaire was distributed to all (n=203) dental
      undergraduates in Years 3 to 5 at the University of Bristol. The questionnaire
      utilised a range of data collection methods including confidence interval ranked
      responses and qualitative measures. The data were analysed using SPSS. RESULTS:
      The response rate was 51%. Undergraduate perception of confidence increased
      throughout the years of study (P<.001). There was also an increase in the number
      of partial and complete denture cases treated as students progressed through the
      course (P<.001). Overall, students were satisfied with their prosthodontic
      teaching, although students thought that too much time was allocated to
      laboratory teaching, and that increasing their clinical experience would be most
      beneficial in increasing their confidence levels. CONCLUSION: Student confidence
      in carrying out prosthetic treatment increased as students progressed through the
      course, and confidence levels would be increased further with increased clinical
      experience.

PMID- 28493629
TI  - It is the time to rethink the criteria to define transplantable kidneys. Should
      we combine histological and clinical evaluation?

PMID- 28493630
TI  - Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a
      nationwide cohort study.
AB  - This was a nationwide cohort study to investigate the impact of anti-A/B and
      donor-specific anti-HLA (HLA-DSA) antibodies on the clinical outcomes in kidney
      transplant recipients (KTRs). We classified a total of 1964 KTRs into four
      groups: transplants from ABO-incompatible donors (ABOi, n = 248); transplants in
      recipients with HLA-DSA (HLAi, n = 144); transplants from combined ABOi and HLAi
      donors (ABOi + HLAi, n = 31); and a control group for whom neither ABOi nor HLAi
      was applicable (CONT, n = 1541). We compared the incidence of biopsy-proven acute
      rejection (BPAR), allograft and patient survival rates. The incidence of BPAR was
      higher in the HLAi and ABOi + HLAi groups relative to the CONT group; in
      contrast, it was not higher in the ABOi group. Death-censored graft survival
      rates did not differ across the four groups. However, relative to the CONT group,
      patient survival rate was reduced in the ABOi and ABOi + HLAi groups, and with
      infection being the most common cause of death. Further, multivariable analysis
      revealed that desensitization therapy because of ABOi or HLAi was independent
      risk factors for patient mortality. HLAi was a more important risk factor for
      BPAR compared with ABOi. However, pretransplant desensitization therapy for
      either ABOi or HLAi significantly increased the risk of infection-related
      mortality.

PMID- 28493632
TI  - Dangerously mixed.

PMID- 28493633
TI  - Capturing the Role of Explicit Solvent in the Dimerization of RuV (bda) Water
      Oxidation Catalysts.
AB  - A ground-breaking empirical valence bond study for a soluble transition-metal
      complex is presented. The full reaction of catalyst monomers approaching and
      reacting in the RuV oxidation state were studied. Analysis of the solvation shell
      in the reactant and along the reaction coordinate revealed that the oxo itself is
      hydrophobic, which adds a significant driving force to form the dimer. The effect
      of the solvent on the reaction between the prereactive dimer and the product was
      small. The solvent seems to lower the barrier for the isoquinoline (isoq) complex
      while it is increased for pyridines. By comparing the reaction in the gas phase
      and solution, the proposed pi-stacking interaction of the isoq ligands is found
      to be entirely driven by the water medium.

PMID- 28493631
TI  - Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and
      meta-analysis.
AB  - BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in
      the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic
      Rhinoconjunctivitis. To inform the development of clinical recommendations, we
      undertook a systematic review to assess the effectiveness, cost-effectiveness,
      and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We
      searched nine international biomedical databases for published, in-progress, and
      unpublished evidence. Studies were independently screened by two reviewers
      against predefined eligibility criteria and critically appraised using
      established instruments. Our primary outcomes of interest were symptom,
      medication, and combined symptom and medication scores. Secondary outcomes of
      interest included cost-effectiveness and safety. Data were descriptively
      summarized and then quantitatively synthesized using random-effects meta
      analyses. RESULTS: We identified 5960 studies of which 160 studies satisfied our
      eligibility criteria. There was a substantial body of evidence demonstrating
      significant reductions in standardized mean differences (SMD) of symptom (SMD 
      0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and
      combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on
      treatment that were robust to prespecified sensitivity analyses. There was in
      comparison a more modest body of evidence on effectiveness post-discontinuation
      of AIT, suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is
      effective in improving symptom, medication, and combined symptom and medication
      scores in patients with allergic rhinoconjunctivitis while on treatment, and
      there is some evidence suggesting that these benefits are maintained in relation
      to symptom scores after discontinuation of therapy.

PMID- 28493634
TI  - An experimental study of the recovery of injured porcine lungs with prolonged
      normothermic cellular ex vivo lung perfusion following donation after circulatory
      death.
AB  - Donation after circulatory death (DCD) is an underused source of donor lungs.
      Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving
      standard donor lungs but may also be useful in the preservation and assessment of
      DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm
      ischemia and postmortem ventilation on graft recovery were evaluated. Adult male
      swine underwent general anesthesia and heparinization. In the control group (n =
      4), cardioplegic arrest was induced and the lungs were procured immediately. In
      the four treatment groups, a period of agonal hypoxia was followed by either 1 h
      of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm
      ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on
      an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on
      EVLP were worse in all DCD lungs compared with controls. Hemodynamics and
      compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated
      impaired oxygenation. Normothermic cellular EVLP is effective in preserving and
      monitoring of DCD lungs. Early donor postmortem ventilation and timely
      procurement lead to improved graft function.

PMID- 28493635
TI  - The double-edged experience of healthcare encounters among women with
      endometriosis: A qualitative study.
AB  - AIMS AND OBJECTIVES: To identify and describe the experience of healthcare
      encounters among women with endometriosis. BACKGROUND: Endometriosis is a
      "hidden" chronic gynaecological disease appearing in every 10th woman of fertile
      age. Different manifestations of pain are the main symptoms, often leading to
      impaired physical and mental health, and lower quality of life. Previous research
      on healthcare experiences among women with endometriosis has focused on
      diagnostic delay and experiences of encountering general practitioners. DESIGN: A
      qualitative, interpretive, phenomenological approach was used. METHODS: We
      interviewed nine women aged 23-55, with a laparoscopy-confirmed diagnosis of
      endometriosis. The interviews were recorded and transcribed verbatim. The data
      were analysed following the steps of the interpretive phenomenological approach.
      RESULTS: Two themes were identified in the interview transcripts: being treated
      with ignorance and being acknowledged. The essence: "the double-edged experience
      of healthcare encounters" emerged from the themes. The women's experience was
      double-edged as it involved contradictory feelings: the encounters were
      experienced as both destructive or constructive. On the one hand, the destructive
      side was characterised by ignorance, exposure and disbelief. On the other hand,
      the constructive side made the women feel acknowledged and confirmed, boosting
      their self-esteem. CONCLUSIONS: The new and important aspects of the findings are
      that the experience of healthcare encounters is for the first time expressed as
      double-edged: both destructive and constructive. The experience was of specific
      importance as it affected the women's perceptions of themselves and of their
      bodies. RELEVANCE TO CLINICAL PRACTICE: The information about the constructive
      side of the experience is of clinical valuable for all healthcare professionals
      (nurses, midwives and doctors) encountering these women, as it provides a new
      level of understanding of the experiences. The findings demonstrate both
      psychological and practical aspects that can help professionals to improve the
      encounters.

PMID- 28493636
TI  - Families' perceptions of the contribution of intellectual disability clinical
      nurse specialists in Ireland.
AB  - AIM AND OBJECTIVES: To explore families' perceptions of the contribution of
      clinical nurse specialists in intellectual disability nursing in Ireland.
      BACKGROUND: Clinical nurse specialists roles have developed over the years and
      are seen as complex and multifaceted, causing confusion, frustration and
      controversy. 2001 saw the formal introduction of clinical nurse specialists roles
      in Ireland across nursing including intellectual disability. DESIGN: A
      exploratory qualitative approach using semistructured one-to-one interviews with
      10 family members regarding their perceptions of the clinical nurse specialists
      in intellectual disability. METHODS: Data were audio-recorded, transcribed and
      analysed using Burnard's framework. Ethical approval was gained and access
      granted by service providers. FINDINGS: The study highlights that intellectual
      disability clinical nurse specialists contribute and support care deliver across
      a range of areas, including personal caring, supporting and empowering families,
      liaison, education and leadership. CONCLUSIONS: Clinical nurse specialists have
      an important role and contribution in supporting families and clients, and
      Ireland is in a unique position to develop knowledge regarding specialist care
      for people with intellectual disability that can be shared nationally and
      internationally. RELEVANCE TO CLINICAL PRACTICE: Ireland is in a unique position
      to develop knowledge regarding specialist care for people with intellectual
      disability that can be shared and adapted by other healthcare professionals in
      other countries that do not have a specialised intellectual disability nurses.

PMID- 28493637
TI  - Single-Molecule Photoactivation FRET: A General and Easy-To-Implement Approach To
      Break the Concentration Barrier.
AB  - Single-molecule fluorescence resonance energy transfer (sm-FRET) has become a
      widely used tool to reveal dynamic processes and molecule mechanisms hidden under
      ensemble measurements. However, the upper limit of fluorescent species used in sm
      FRET is still orders of magnitude lower than the association affinity of many
      biological processes under physiological conditions. Herein, we introduce single
      molecule photoactivation FRET (sm-PAFRET), a general approach to break the
      concentration barrier by using photoactivatable fluorophores as donors. We
      demonstrate sm-PAFRET by capturing transient FRET states and revealing new
      reaction pathways during translation using MUm fluorophore labeled species, which
      is 2-3 orders of magnitude higher than commonly used in sm-FRET measurements. sm
      PAFRET serves as an easy-to-implement tool to lift the concentration barrier and
      discover new molecular dynamic processes and mechanisms under physiological
      concentrations.

PMID- 28493638
TI  - Chemically Controlled Spatiotemporal Oscillations of Colloidal Assemblies.
AB  - We report an autonomous oscillatory micromotor system in which active colloidal
      particles form clusters, the size of which changes periodically. The system
      consists of an aqueous suspension of silver orthophosphate microparticles under
      UV illumination, in the presence of varying concentrations of hydrogen peroxide.
      The colloid particles first attract each other to form clusters. After a short
      delay, these clusters abruptly disperse and oscillation begins, alternating
      between clustering and dispersion of particles. After a cluster oscillation
      initiates, the oscillatory wave propagates to nearby clusters and eventually all
      the clusters oscillate in phase-shifted synchrony. The oscillatory behavior is
      governed by an electrolytic self-diffusiophoretic mechanism which involves
      alternating electric fields generated by the competing reduction and oxidation of
      silver. The oscillation frequency is tuned by changing the concentration of
      hydrogen peroxide. The addition of inert silica particles to the system results
      in hierarchical sorting and packing of clusters. Densely packed Ag3 PO4 particles
      form a non-oscillating core with an oscillating shell composed largely of silica
      microparticles.

PMID- 28493639
TI  - Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation
      of Alkenes with Alcohols.
AB  - A conceptually novel strategy with achiral pyridine as the ancillary ligand to
      stabilize high-valent copper species for the first asymmetric radical
      oxytrifluoromethylation of alkenes with alcohols under CuI /phosphoric acid dual
      catalysis has been developed. The transformation features mild reaction
      conditions, a remarkably broad substrate scope and excellent functional group
      tolerance, offering an efficient approach to a wide range of trifluoromethyl
      substituted tetrahydrofurans bearing an alpha-tertiary stereocenter with
      excellent enantioselectivity. Mechanistic studies support the presumed role of
      the achiral pyridine as a coordinative ligand on copper metal to stabilize the
      key transient reaction species involved in the asymmetric induction process.

PMID- 28493640
TI  - Synthesis of Dibenzo[hi,st]ovalene and Its Amplified Spontaneous Emission in a
      Polystyrene Matrix.
AB  - A large number of graphene molecules, or large polycyclic aromatic hydrocarbons
      (PAHs), have been synthesized and display various optoelectronic properties.
      Nevertheless, their potential for application in photonics has remained largely
      unexplored. Herein, we describe the synthesis of a highly luminescent and stable
      graphene molecule, namely a substituted dibenzo[hi,st]ovalene (DBO 1), with
      zigzag edges and elucidate its promising optical-gain properties by means of
      ultrafast transient absorption spectroscopy. Upon incorporation of DBO into an
      inert polystyrene matrix, amplified stimulated emission can be observed with a
      relatively low power threshold (ca. 60 MUJ cm-2 ), thus highlighting its high
      potential for lasing applications.

PMID- 28493641
TI  - Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical
      outcomes following transcatheter aortic valve replacement: Results from the BRAVO
      3 randomized trial.
AB  - BACKGROUND: Prior studies have suggested that patients with atrial fibrillation
      (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk
      for adverse cardiovascular events. Whether procedural bivalirudin compared with
      unfractionated heparin (UFH) has a beneficial effect on early outcomes in these
      patients is unknown. We examined for the effect of baseline or new-onset AF
      within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by
      AF status, on 30-day outcomes from the BRAVO 3 trial. METHODS: The BRAVO-3 trial
      multicenter randomized trial included 802 patients undergoing transfemoral TAVR
      randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined
      for 30-day Bleeding Academic Research Consortium type >=3b bleeding, major
      vascular complications and all ischemic endpoints. Adjusted outcomes were
      analyzed using logistic regression methods. RESULTS: Of the study population,
      41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR,
      whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of
      renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE
      I compared with their counterparts without AF. Among AF and no-AF patients, there
      were no significant baseline differences between bivalirudin and UFH groups. At
      30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs.
      2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n =
      38) was associated with significantly greater crude risk of 30-day stroke
      compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there
      were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by
      anticoagulation type. CONCLUSIONS: Prior or new-onset AF is noted in more than
      one-third of patients undergoing transfemoral TAVR. Despite greater baseline
      comorbidities than non-AF patients, AF was not associated with significantly
      higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes
      were similar regardless of anticoagulant strategy in each group.

PMID- 28493644
TI  - The quality of life of people who have chronic wounds and who self-treat.
AB  - AIMS AND OBJECTIVES: The aim of this study was to investigate the effect of
      chronic wounds on the physical, emotional, social, lifestyle and financial
      domains of quality of life among people who self-treat their wounds. BACKGROUND:
      Patient-centred models of care have received increased attention over recent
      decades because of the potential to contribute positively to the patient's health
      and well-being. A contemporary understanding of the effect of chronic wounds on
      quality of life may assist care providers and healthcare systems to respond to
      patient needs and improve patient outcomes. METHOD: A qualitative, exploratory
      study was conducted in Victoria, Australia. Participants were aged 18 years or
      older and had a chronic wound that was currently or previously self-treated. A
      sample of 25 participants was recruited from the community, and in-depth
      interviews were conducted in participants' homes. A thematic analysis was
      conducted to identify themes that represented the physical, emotional, social,
      lifestyle and financial domains of quality of life. RESULTS: Study participants
      (n = 25) were 71 years of age (average), and the majority had a leg wound.
      Participants experienced a negative effect on quality of life. Physical
      limitations affected activity and compromised the management of other health
      conditions. Participants felt frustrated with and distrusting of healthcare
      professionals from whom they received advice and care. Daily lifestyle and
      workforce participation were disrupted when receiving professional care. Wound
      treatment and professional care expenses negatively affected personal finances.
      CONCLUSION: Continued effort is required to develop relationships and treatment
      regimens that are conducive to healing and to optimise well-being. Additionally,
      healthcare systems should identify and address structural shortcomings of care
      services to create more patient-centred models of wound care in the community
      setting.

PMID- 28493642
TI  - Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A
      Double-blind, Randomized Controlled Trial.
AB  - OBJECTIVES: The goal of our study was to compare the frequency and severity of
      recovery reactions between ketamine and ketamine-propofol 1:1 admixture
      ("ketofol"). METHODS: We performed a multicentric, randomized, double-blind trial
      in which adult patients received emergency procedural sedations with ketamine or
      ketofol. Our primary outcome was the proportion of unpleasant recovery reactions.
      Other outcomes were frequency of interventions required by these recovery
      reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction
      of patients as well as providers. RESULTS: A total of 152 patients completed the
      study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction
      in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic
      interventions required by these reactions. There was no serious adverse event in
      both groups. Rates in hemodynamic or respiratory events as well as satisfaction
      scores were similar. Significantly fewer patients experienced emesis with
      ketofol, with a threefold reduction in incidence compared with ketamine.
      CONCLUSION: We found a significant reduction in recovery reactions and emesis
      frequencies among adult patients receiving emergency procedural sedations with
      ketofol, compared with ketamine.

PMID- 28493645
TI  - Carbon-Fluorine Reductive Elimination from Nickel(III) Complexes.
AB  - We report a C-F reductive elimination from a characterized first-row aryl metal
      fluoride complex. Reductive elimination from the presented nickel(III) complexes
      is faster than C-F bond formation from any other characterized aryl metal
      fluoride complex.

PMID- 28493646
TI  - Validation of the No Objective Testing Rule and Comparison to the HEART Pathway.
AB  - BACKGROUND: The no objective testing rule (NOTR) is a decision aid designed to
      safely identify emergency department (ED) patients with chest pain who do not
      require objective testing for coronary artery disease. OBJECTIVES: The objective
      was to validate the NOTR in a cohort of U.S. ED patients with acute chest pain
      and compare its performance to the HEART Pathway. METHODS: A secondary analysis
      of 282 participants enrolled in the HEART Pathway randomized controlled trial was
      conducted. Each patient was classified as low risk or at risk by the NOTR.
      Sensitivity for major adverse cardiac events (MACE) at 30 days was calculated in
      the entire study population. NOTR and HEART Pathways were compared among patients
      randomized to the HEART Pathway in the parent trial using McNemar's test and the
      net reclassification improvement (NRI). RESULTS: Major adverse cardiac events
      occurred in 22/282 (7.8%) participants, including no deaths, 16/282 (5.6%) with
      myocardial infarction (MI), and 6/282 (2.1%) with coronary revascularization
      without MI. NOTR was 100% (95% confidence interval [CI] = 84.6%-100%) sensitive
      for MACE and identified 78/282 patients (27.7%, 95% = CI 22.5-33.3%) as low risk.
      In the HEART Pathway arm (n = 141), both NOTR and HEART Pathway identified all
      patients with MACE as at risk. Compared to NOTR, the HEART Pathway was able to
      correctly reclassify 27 patients without MACE as low risk, yielding a NRI of
      20.8% (95% CI = 11.3%-30.2%). CONCLUSIONS: Within a U.S. cohort of ED patients
      with chest pain, the NOTR and HEART Pathway were 100% sensitive for MACE at 30
      days. However, the HEART Pathway identified more patients suitable for early
      discharge than the NOTR.

PMID- 28493647
TI  - The liminality of the patient with dementia in hospital.
AB  - AIMS AND OBJECTIVES: The aim was to explore the experiences of people with
      dementia in subacute geriatric rehabilitation hospitals to critically evaluate
      the care received by such patients. BACKGROUND: Globally, the number of people
      with dementia is growing and is expected to impact progressively more on health
      systems. People with dementia can become deconditioned and deteriorate in
      cognitive function while in hospital. The unfamiliar environment and people can
      cause the person to become disorientated, which then leads to behavioural
      symptoms which complicate care. DESIGN: Critical ethnography. METHODS: Methods
      included observation with field notes and 30 audio-recorded conversational
      interviews with patients with dementia in an Australian subacute care setting.
      Data were collected in May-December 2014, transcribed verbatim and analysed using
      thematic analysis. RESULTS: The central theme identified that patients with
      dementia described a liminal experience and felt like outsiders in the hospital
      environment. This was supported by the subthemes of not understanding why they
      were being kept in hospital, feeling lost in the space, bored, anxious about
      discharge plans and lacking intersubjective relationships. Many felt imprisoned
      by the locked wards. There was little evidence of nursing care delivered in an
      empathetic person-centred way. Nurses were busy and engaged with the patients
      only superficially. CONCLUSIONS: People with dementia can have a liminal
      experience and feel like outsiders in this environment, which does not cater for
      the specific needs of this patient group. It should be acknowledged that people
      with dementia require additional resources. A caring nurse-patient relationship
      is fundamental to the patient experience. Nurses require further support and
      education about dementia in order to deliver quality care to this patient group.
      RELEVANCE TO CLINICAL PRACTICE: These findings will influence nurse leaders to
      advocate for improved resources for nurses to provide appropriate care for
      patients with dementia in subacute geriatric hospitals. The clinical practice of
      nurses needs to be supported with education, pyschological and material support
      to improve the therapeutic environment for patients with cognitive impairment
      resulting from dementia.

PMID- 28493648
TI  - Detection of Localized Hepatocellular Amino Acid Kinetics by using Mass
      Spectrometry Imaging of Stable Isotopes.
AB  - Mass spectrometry imaging (MSI) simultaneously detects and identifies the spatial
      distribution of numerous molecules throughout tissues. Currently, MSI is limited
      to providing a static and ex vivo snapshot of highly dynamic systems in which
      molecules are constantly synthesized and consumed. Herein, we demonstrate an
      innovative MSI methodology to study dynamic molecular changes of amino acids
      within biological tissues by measuring the dilution and conversion of stable
      isotopes in a mouse model. We evaluate the method specifically on hepatocellular
      metabolism of the essential amino acid l-phenylalanine, associated with liver
      diseases. Crucially, the method reveals the localized dynamics of l-phenylalanine
      metabolism, including its in vivo hydroxylation to l-tyrosine and co-localization
      with other liver metabolites in a time course of samples from different animals.
      This method thus enables the dynamics of localized biochemical synthesis to be
      studied directly from biological tissues.

PMID- 28493649
TI  - Temperature-Driven Planar Chirality Switching of a Pillar[5]arene-Based Molecular
      Universal Joint.
AB  - The study of an enantiopure bicyclic pillar[5]arene-based molecular universal
      joint (MUJ) by single-crystal X-ray diffraction allowed for the first time the
      unequivocal assignment of the absolute configuration of a planar chiral
      pillar[5]arene by circular dichroism spectroscopy. Crucially, the absolute
      configuration of the MUJ was switched reversibly by temperature, with an
      accompanying sign inversion of the anisotropy factor that varied by as much as
      0.03, which is the largest value ever reported. Mechanistically, the reversible
      chirality switching of the MUJ is driven by the threading/dethreading motion of
      the fused ring and hence is dependent on both the size and nature of the ring and
      the solvent employed, reflecting the critical balance between the self
      complexation of the ring by pillar[5]arene, the solvation to the excluded ring,
      and the inclusion of solvent molecules in the cavity.

PMID- 28493650
TI  - Pro-survival redox signalling in progesterone-mediated retinal neuroprotection.
AB  - Retinitis pigmentosa (RP) is a group of hereditary retinal diseases,
      characterised by photoreceptor cell loss. Despite a substantial understanding of
      the mechanisms leading to cell death, an effective therapeutic strategy is
      sought. Our laboratory has previously demonstrated the neuroprotective properties
      of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in
      part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other
      retinal studies, we have also presented a pro-survival role for reactive oxygen
      species (ROS), downstream of bFGF. Thus, we hypothesized that Norgestrel utilises
      bFGF-driven ROS production to promote photoreceptor survival. Using the 661W
      photoreceptor-like cell line, we now show that Norgestrel, working through
      progesterone receptor membrane complex 1 (PGRMC1); generates an early burst of
      pro-survival bFGF-induced ROS. Using the rd10 mouse model of RP, we confirm that
      Norgestrel induces a similar early pro-survival increase in retinal ROS.
      Norgestrel-driven protection in the rd10 retina was attenuated in the presence of
      antioxidants. This study therefore presents an essential role for ROS signalling
      in Norgestrel-mediated neuroprotection in vitro and demonstrates that Norgestrel
      employs a similar pro-survival mechanism in the degenerating retina.

PMID- 28493651
TI  - Hydroxoiridium-Catalyzed Hydroalkylation of Terminal Alkenes with Ureas by C(sp3
      )-H Bond Activation.
AB  - Direct alkylation of a methyl group, on di- and trisubstituted ureas, with
      terminal alkenes by C(sp3 )-H bond activation proceeded in the presence of a
      hydroxoiridium/bisphosphine catalyst to give high yields of the corresponding
      addition products. The hydroxoiridium/bisphosphine complex generates an
      amidoiridium intermediate by reaction with ureas having an N-H bond.

PMID- 28493652
TI  - Vitamin D Deficiency Associated With Cognitive Functioning in Psychotic
      Disorders.
AB  - BACKGROUND: Cognitive dysfunctions are core features of psychotic disorders with
      substantial impact on daily functioning. Vitamin D deficiency has been found to
      be related to cognitive dysfunctions, but the associations between vitamin D
      deficiency and cognition in persons with a psychotic disorder are largely
      unknown. METHODS: This cross-sectional study included 225 patients with a DSM-IV
      psychotic disorder consecutively recruited from 2003 to 2014 and 159 randomly
      selected healthy controls, assessed by a cognitive test battery, a clinical
      protocol (including Structured Clinical Interview for DSM-IV Axis I Disorders and
      Positive and Negative Syndrome Scale), and a physical examination including
      vitamin D measurements. Multiple regression models were performed to evaluate the
      effect of vitamin D deficiency (defined serum 25-hydroxyvitamin D [25(OH)D] < 25
      nmol/L) on key cognitive domains: processing speed, verbal learning, verbal
      memory, and executive functioning. RESULTS: Vitamin D deficiency was
      significantly associated with decreased processing speed (ie, Digit Symbol
      Coding) (t = -2.6, P = .01; total model: adjusted R2 = 0.40, F6, 374 = 43.8, P <
      .001) and decreased fluency (ie, verbal fluency) (t = -2.1, P = .04; total model:
      adjusted R2 = 0.35, F6, 373 = 34.2, P < .001) when the results were controlled
      for age, ethnicity, IQ, patient versus control status, and substance or alcohol
      abuse. Additional analyses indicated that negative symptoms diluted the
      association between vitamin D deficiency and processing speed (t = -1.72, P =
      .09) and verbal fluency (t = -1.35, P = .18) in patients. CONCLUSION: The
      associations between vitamin D deficiency and processing speed and verbal fluency
      are good arguments for planning large-scale randomized controlled studies in
      target populations so conclusions can be made about the potential beneficial
      effect of vitamin D on cognition in psychotic disorders.

PMID- 28493653
TI  - Technology-Assisted Parent Training Programs for Children and Adolescents With
      Disruptive Behaviors: A Systematic Review.
AB  - OBJECTIVE: To systematically review digitally assisted parent training programs
      (DPTs) targeting the treatment of children and adolescents with disruptive
      behaviors. DATA SOURCES: A search was conducted using PubMed, PsycINFO, and
      EMBASE databases for peer-reviewed studies published between January 1, 2000, and
      March 1, 2016. Reference lists of included and review articles were searched
      manually for additional references. STUDY SELECTION: Broad search terms in
      varying combinations for parent, training, technologies, and disruptive behavior
      problems were used. We included English-language articles reporting on the
      effectiveness of DPTs targeting child or adolescent disruptive behaviors (eg,
      conduct disorder, oppositional defiant disorder). DPTs designed to use digital
      media or software programs not to be primarily used within a therapy setting (eg,
      group, face-to-face) were included. DATA EXTRACTION: Study design, recruitment
      and sample characteristics, theoretical background, digital program features,
      user's engagement, and measures of child behavior were extracted. RESULTS:
      Fourteen intervention studies (n = 2,427, 58% male, 1,500 in DPT conditions, 12
      randomized trials) examining 10 programs met inclusion criteria. Interventions
      included self-directed noninteractive (eg, podcasts; 3 studies) and interactive
      (eg, online software; 4 studies) DPTs, remotely administered DPTs combined with
      professional phone-based coaching (2 studies), and a smartphone enhancement of
      standard treatment. Interventions were delivered over a mean +/- SD period of 8.7
      +/- 4.2 weeks, most (11/14; 78.6%) were remotely administered, and all
      recruitment procedures included an outreach for parents outside of mental health
      care settings. For programs with > 5 sessions, the mean +/- SD completion rate of
      available sessions was 68.6% +/- 13.1%. In comparison to no treatment control,
      self-directed programs yielded significant improvements in child behavior for
      children (age < 9 years, Cohen d = 0.47-0.80, 4 studies) and adolescents (d =
      0.17, 0.20, 2 studies). Overall, reduced professional support combined with DPT
      was not inferior to full-contact conditions and showed small improvement in
      comparison to usual care (d = 0.34). Preliminary indicators also suggested that
      technology enhancements may increase engagement and outcomes of standard
      treatment. CONCLUSIONS: The current review indicates the efficacy of DPT across a
      range of therapy formats applied in real-world settings demonstrating the
      potential for increased accessibility of evidence-based treatment for youth with
      disruptive behaviors. Additional studies are needed to extend these findings and
      to determine moderating effects of different designs.

PMID- 28493655
TI  - Development of a Computerized Adaptive Test Suicide Scale-The CAT-SS.
AB  - OBJECTIVE: Current suicide risk screening and measurement are inefficient, have
      limited measurement precision, and focus entirely on suicide-related items. For
      this study, a psychometric harmonization between related suicide, depression, and
      anxiety symptom domains that provides a more balanced and complete spectrum of
      suicidal symptomatology was developed. The objective of this article is to
      describe the results of the early stages of computerized adaptive testing
      development for a suicide scale and pave the way for the final stage of
      validation. METHODS: Data from psychiatric outpatients at the University of
      Pittsburgh and a community health clinic were collected from January 2010 through
      June 2012. 789 participants were enrolled in the calibration phase; 70% were
      female, and 30% were male. The rate of major depressive disorder as diagnosed by
      DSM-5 was 47%. The item bank contained 1,008 items related to depression,
      anxiety, and mania, including 11 suicide items. Data were analyzed using a
      bifactor model to identify a core dimension between suicidal ideation,
      depression, anxiety, and mania items. A computerized adaptive test was developed
      via simulation from the actual complete item responses in 308 subjects. RESULTS:
      111 items were identified that provided an extension of suicidality assessment to
      include statistically related responses from depression and anxiety domains that
      are syndromally associated with suicidality. All items had high loadings on the
      primary suicide dimension (average = 0.67; range, 0.49-0.88). Analyses revealed
      that a mean of 10 items (5-20) had a correlation of 0.96 with the 111-item scale,
      with a precision of 5 points on a 100-point scale metric. Preliminary validation
      data based on 290 clinician interviews revealed a 52-fold increase in the
      likelihood of current suicidal ideation across the range of the Computerized
      Adaptive Test Suicide Scale (CAT-SS). CONCLUSIONS: The CAT-SS is able to
      accurately measure the latent suicide dimension with a mean of 10 items in
      approximately 2 minutes. Further validation against an independent clinician
      administered assessment of suicide risk (ideation and attempts) and prediction of
      suicidal behavior is underway.

PMID- 28493654
TI  - The US Food and Drug Administration's Perspective on the New Antipsychotic
      Pimavanserin.
AB  - OBJECTIVE: To summarize the US Food and Drug Administration's (FDA's) review of
      the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the
      treatment of hallucinations and delusions associated with Parkinson's disease
      psychosis. We describe the regulatory and clinical issues important to the FDA's
      approval of this New Drug Application, with special focus on the risk-benefit
      balance. We also describe a new labeling feature that presents additional
      efficacy data to clinicians. DATA SOURCES: Data sets for all relevant clinical
      trials of pimavanserin and the Applicant's and FDA's analyses of these data were
      considered in this review. Data were available from 616 patients with Parkinson's
      disease with hallucinations and delusions who received at least 1 dose of
      pimavanserin, with a total exposure of 825 patient-years in the Parkinson's
      disease psychosis population. RESULTS: Pimavanserin 34 mg/d was effective in
      treating hallucinations and delusions associated with Parkinson's disease. In the
      Applicant's single pivotal trial, 80.5% of pimavanserin patients experienced at
      least some improvement in symptoms compared to 58.1% of patients taking placebo.
      Pimavanserin did not worsen motor function, an adverse effect commonly observed
      with other antipsychotics, probably because of a lack of consequential dopamine
      binding. CONCLUSIONS: Pimavanserin is the only FDA-approved treatment for the
      hallucinations and delusions seen in patients with psychosis of Parkinson's
      disease. Although pimavanserin appears to have a pharmacologic mechanism that is
      different from other atypical antipsychotics, concern remained that the increased
      risk of death seen with antipsychotic use in elderly demented patients, and
      described in all approved antipsychotic labels, would also occur with
      pimavanserin. Pimavanserin bears the same boxed warning about the risk of death
      associated with antipsychotic use in elderly patients with dementia.

PMID- 28493656
TI  - Perceived Stigma and Quality of Life in Patients Following Recovery From
      Delirium.
AB  - OBJECTIVE: To elucidate the factors related to perceived stigma and quality of
      life (QoL) in patients who have recovered from delirium. METHODS: This
      prospective cohort investigation of patients with delirium, as diagnosed
      according to DSM-IV-TR criteria, was conducted from July 2011 to May 2013. The
      perceived stigma level and QoL of each patient was assessed using the Perceived
      Stigma of Delirium Scale (PSDS) and European Quality of Life Visual Analog Scale
      (EQ-VAS), respectively, following recovery from delirium. Several clinical
      characteristics were assessed at baseline and after recovery from delirium, and a
      multivariate linear regression analysis was conducted. RESULTS: This study
      included 128 patients who completed a follow-up assessment after recovery from
      delirium. A multivariate analysis revealed that patients who had a history of
      depression (B = 3.34, P = .026), could recall their experiences with delirium (B
      = 1.71, P = .011), and had a longer duration from delirium detection to recovery
      (B = 1.39, P = .012) obtained higher PSDS scores than patients without these
      characteristics. The ability to recall delirium experiences (B = -7.17, P = .026)
      and the use of antipsychotics at follow-up assessment (B = -7.87, P = .039) were
      associated with lower EQ-VAS scores. Additionally, PSDS scores were negatively
      correlated with EQ-VAS scores (r = -0.37, P < .001). CONCLUSIONS: This study
      found that patients who experienced an episode of delirium reported varying
      degrees of perceived stigma and that the ability to recall their delirium
      experiences was associated with a higher stigma and a poorer QoL. These findings
      suggest that care teams should pay more attention to perceived stigma in patients
      with delirium.

PMID- 28493657
TI  - Introduction.
AB  - We are pleased to bring you the second of two special issues on mood and anxiety
      disorders focussing on data from the 2014 Survey on Living with Chronic Diseases
      in Canada-Mood and Anxiety Disorder Component (SLCDC-MA). In December of 2016, we
      published the first issue, which included three articles describing various
      aspects of Canadian adults with a self-reported diagnosed mood and/or anxiety
      disorder including their sociodemographic characteristics, health status,
      activity limitations and level of disability and factors associated with well
      being. The three articles in this (second) issue investigate topics related to
      the management of these disorders. Collectively, the articles explore key
      sociodemographic factors known to influence health-related outcomes and discuss
      strategies aimed at promoting the recovery and well-being of Canadian adults with
      a self-reported mood and/or anxiety disorder diagnosis.

PMID- 28493658
TI  - Factors associated with delayed diagnosis of mood and/or anxiety disorders.
AB  - INTRODUCTION: This study examined the association between time to diagnosis and
      sociodemographic and clinical characteristics as well as time to diagnosis and
      physical and mental health status, among Canadian adults with a self-reported
      mood and/or anxiety disorder diagnosis. METHODS: We used data from the 2014
      Survey on Living with Chronic Diseases in Canada-Mood and Anxiety Disorders
      Component. The study sample (n=3212) was divided into three time to diagnosis
      subgroups: long (> 5 years), moderate (1-5 years) and short (< 1 year). We
      performed descriptive and multinomial multivariate logistic regression analyses.
      Estimates were weighted to represent the Canadian adult household population
      living in the 10 provinces with diagnosed mood and/or anxiety disorders. RESULTS:
      The majority (61.6%) of Canadians with a mood and/or anxiety disorder diagnosis
      reported having received their diagnosis more than one year after symptom onset
      (30.0% reported a moderate delay and 31.6% a long delay). Upon controlling for
      individual characteristics, we found significant associations between a moderate
      delay and having no or few physical comorbidities; a long delay and older age;
      and both moderate and long delays and early age of symptom onset. In addition, a
      long delay was significantly associated with "poor" or "fair" perceived mental
      health and the greatest number of activity limitations. CONCLUSION: These
      findings affirm that a long delay in diagnosis is associated with negative health
      outcomes among Canadian adults with mood and/or anxiety disorders. Time to
      diagnosis is particularly suboptimal among older adults and people with early
      symptom onset. Tailored strategies to facilitate an early diagnosis for those at
      greatest risk of a delayed diagnosis, especially for those with early symptom
      onset, are needed.

PMID- 28493659
TI  - Self-management of mood and/or anxiety disorders through physical
      activity/exercise.
AB  - INTRODUCTION: Physical activity/exercise is regarded as an important self
      management strategy for individuals with mental illness. The purpose of this
      study was to describe individuals with mood and/or anxiety disorders who were
      exercising or engaging in physical activity to help manage their disorders versus
      those who were not, and the facilitators for and barriers to engaging in physical
      activity/exercise. METHODS: For this study, we used data from the 2014 Survey on
      Living with Chronic Diseases in Canada-Mood and Anxiety Disorders Component.
      Selected respondents (n = 2678) were classified according to the frequency with
      which they exercised: (1) did not exercise; (2) exercised 1 to 3 times a week; or
      (3) exercised 4 or more times a week. We performed descriptive and multinomial
      multiple logistic regression analyses. Estimates were weighted to represent the
      Canadian adult household population living in the 10 provinces with diagnosed
      mood and/or anxiety disorders. RESULTS: While 51.0% of the Canadians affected
      were not exercising to help manage their mood and/or anxiety disorders, 23.8%
      were exercising from 1 to 3 times a week, and 25.3% were exercising 4 or more
      times a week. Increasing age and decreasing levels of education and household
      income adequacy were associated with increasing prevalence of physical
      inactivity. Individuals with a mood disorder (with or without anxiety) and those
      with physical comorbidities were less likely to exercise regularly. The most
      important factor associated with engaging in physical activity/exercise was to
      have received advice to do so by a physician or other health professional. The
      most frequently cited barriers for not exercising at least once a week were as
      follows: prevented by physical condition (27.3%), time constraints/too busy
      (24.1%) and lack of will power/self-discipline (15.8%). CONCLUSION: Even though
      physical activity/exercise has been shown beneficial for depression and anxiety
      symptoms, a large proportion of those with mood and/or anxiety disorders did not
      exercise regularly, particularly those affected by mood disorders and those with
      physical comorbidities. It is essential that health professionals recommend
      physical activity/exercise to their patients, discuss barriers and support their
      engagement.

PMID- 28493661
TI  - Letter to the Editor - The implications of the professionalization of health
      promotion in Canada: a response to JR Graham's letter to the editor.
AB  - This letter is in response to the following Letter to the Editor: http://www.phac
      aspc.gc.ca/publicat/hpcdp-pspmc/37-1/ar-04-eng.php.

PMID- 28493662
TI  - Implementing the New ANA Standard 8: Culturally Congruent Practice
AB  - The American Nurses Association (ANA) is responsible for the contract between
      society and the nursing profession, including the nursing scope and standards of
      practice. In 2015, an ANA workgroup produced Nursing: Scope and Standards of
      Practice, 3rd Ed during a time of social change and an increase of culturally and
      ethnically diverse consumers. Subsequently, a subset of workgroup members and an
      invited transcultural nursing expert led to the creation of the new Standard 8:
      Culturally Congruent Practice, describing nursing care that is in agreement with
      the preferred values, beliefs, worldview, and practices of the healthcare
      consumer. This article records the history of the revised scope and standards and
      new Standard 8, the reasoning behind this standard and its impact on nursing
      practice, education, and research. The article also guides nurses in the
      application of Standard 8 to nursing practice and offers discussion about
      implementing culturally congruent practice through the nursing process. We also
      discuss cultural congruence for the graduate-prepared nurse; offer brief comments
      related to evaluation of culturally congruent practice using Standard 8 and
      future research; and conclude with a call to action.

PMID- 28493660
TI  - Use of medication and psychological counselling among Canadians with mood and/or
      anxiety disorders.
AB  - INTRODUCTION: This study describes the use of prescription medications and
      psychological counselling in the past 12 months among Canadian adults with a self
      reported mood and/or anxiety disorder diagnosis; the sociodemographic and
      clinical characteristics associated with their use; and reasons for not using
      them. METHODS: We used data from the 2014 Survey on Living with Chronic Diseases
      in Canada-Mood and Anxiety Disorders Component. The study sample (n = 2916) was
      divided into four treatment subgroups: (1) taking medication only; (2) having
      received counselling only; (3) both; or (4) neither. We combined the first three
      subgroups and carried out descriptive and multivariate logistic regression
      analyses comparing those who are taking medication and/or have received
      counselling in the past 12 months, versus those doing neither. Estimates were
      weighted to represent the Canadian adult household population living in the 10
      provinces with diagnosed mood and/or anxiety disorders. RESULTS: The majority
      (81.8%) of Canadians with a mood and/or an anxiety disorder diagnosis reported
      they are taking medications and/or have received counselling (47.6% taking
      medications only; 6.9% received counselling only; and 27.3% taking/having
      received both). Upon controlling for individual characteristics, taking
      medications and/or having received counselling was significantly associated with
      older age; higher household income; living in the Atlantic region or Quebec
      versus Ontario; and having concurrent disorders or mood disorders only. Symptoms
      controlled without medication was the most common reason for not taking
      medications, while preferring to manage on their own and taking medications were
      among the common reasons for not having received counselling. CONCLUSION: The
      majority of Canadian adults with a mood and/or an anxiety disorder diagnosis are
      taking medications, while few have received counselling. Insights gained
      regarding the factors associated with these treatments, and reasons for not using
      them, emphasize the importance of discussing treatment options and perceived
      barriers with patients to ensure they receive the best treatment according to
      their needs and preference.

PMID- 28493663
TI  - Gate-Tunable Electron Injection Based Organic Light-Emitting Diodes for Low-Cost
      and Low-Voltage Active Matrix Displays.
AB  - Low-cost and low-voltage active matrix displays were fabricated by simply
      patterning gate electrode arrays on a polymer electrolyte (PE)-coated polymer
      light-emitting diode (PLED). Structurally, a PE capacitor seamlessly stacked on a
      PLED by sharing a common Al:LiF composite electrode (PEC|PLED). This monolithic
      integrated organic optoelectronic device was characterized and interpreted as the
      tunable work function (surface potential) because of the perturbation of
      accumulated ions on Al:LiF composite electrode by PEC charging and discharging.
      The modulation of electron injection by the PEC resulted in increases in the
      electroluminescent brightness, from <100 cd m-2 to >8000 cd m-2, and the external
      quantum efficiency from <0.025% to 2.4%.

PMID- 28493664
TI  - Structure and Spectroscopy of Alkene-Cleaving Dioxygenases Containing an
      Atypically Coordinated Non-Heme Iron Center.
AB  - Carotenoid cleavage oxygenases (CCOs) are non-heme iron enzymes that catalyze
      scission of alkene groups in carotenoids and stilbenoids to form biologically
      important products. CCOs possess a rare four-His iron center whose resting-state
      structure and interaction with substrates are incompletely understood. Here, we
      address this knowledge gap through a comprehensive structural and spectroscopic
      study of three phyletically diverse CCOs. The crystal structure of a fungal
      stilbenoid-cleaving CCO, CAO1, reveals strong similarity between its iron center
      and those of carotenoid-cleaving CCOs, but with a markedly different substrate
      binding cleft. These enzymes all possess a five-coordinate high-spin Fe(II)
      center with resting-state Fe-His bond lengths of ~2.15 A. This ligand set
      generates an iron environment more electropositive than those of other non-heme
      iron dioxygenases as observed by Mossbauer isomer shifts. Dioxygen (O2) does not
      coordinate iron in the absence of substrate. Substrates bind away (~4.7 A) from
      the iron and have little impact on its electronic structure, thus excluding
      coordination-triggered O2 binding. However, substrate binding does perturb the
      spectral properties of CCO Fe-NO derivatives, indicating proximate organic
      substrate and O2-binding sites, which might influence Fe-O2 interactions.
      Together, these data provide a robust description of the CCO iron center and its
      interactions with substrates and substrate mimetics that illuminates
      commonalities as well as subtle and profound structural differences within the
      CCO family.

PMID- 28493667
TI  - Scaffold Diversity from N-Acyliminium Ions.
AB  - N-Acyliminium ions are powerful reactive species for the formation of carbon
      carbon and carbon-heteroatom bonds. Strategies relying on intramolecular
      reactions of N-acyliminium intermediates, also referred to as N-acyliminium ion
      cyclization reactions, have been employed for the construction of structurally
      diverse scaffolds, ranging from simple bicyclic skeletons to complex polycyclic
      systems and natural-product-like compounds. This review aims to provide an
      overview of cyclization reactions of N-acyliminium ions derived from various
      precursors for the assembly of structurally diverse scaffolds, covering the
      literature over the past 12 years (from 2004 to 2015).

PMID- 28493666
TI  - Flexible Transparent Supercapacitors Based on Hierarchical Nanocomposite Films.
AB  - Flexible transparent electronic devices have recently gained immense popularity
      in smart wearable electronics and touch screen devices, which accelerates the
      development of the portable power sources with reliable flexibility, robust
      transparency and integration to couple these electronic devices. For potentially
      coupled as energy storage modules in various flexible, transparent and portable
      electronics, the flexible transparent supercapacitors are developed and assembled
      from hierarchical nanocomposite films of reduced graphene oxide (rGO) and aligned
      polyaniline (PANI) nanoarrays upon their synergistic advantages. The
      nanocomposite films are fabricated from in situ PANI nanoarrays preparation in a
      blended solution of aniline monomers and rGO onto the flexible, transparent, and
      stably conducting film (FTCF) substrate, which is obtained by coating silver
      nanowires (Ag NWs) layer with Meyer rod and then coating of rGO layer on
      polyethylene terephthalate (PET) substrate. Optimization of the transparency, the
      specific capacitance, and the flexibility resulted in the obtained all-solid
      state nanocomposite supercapacitors exhibiting enhanced capacitance performance,
      good cycling stability, excellent flexibility, and superior transparency. It
      provides promising application prospects for exploiting flexible, low-cost,
      transparent, and high-performance energy storage devices to be coupled into
      various flexible, transparent, and wearable electronic devices.

PMID- 28493665
TI  - MnO2 Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live
      Cells.
AB  - Sensitive assay and imaging of multiple low-abundance microRNAs (miRNAs) in
      living cells remain a grand challenge. Herein, based on polyelectrolyte-induced
      reduction, a facile approach has been proposed to synthesize novel MnO2
      nanotubes. Owing to the remarkably strong fluorescence quenching ability, low
      cytotoxicity, and excellent colloid stability, the as-prepared MnO2 nanotubes
      showed great potential for simultaneous detection and imaging of multiple miRNAs
      in vitro and in situ in living cells for the first time. Besides, MnO2 nanotubes
      can be reduced to Mn2+ by intracellular acid pH or glutathione, which may serve
      as an activatable contrast reagent for MRI. Therefore, the MnO2 nanotube-based
      probes, termed "NanoSearchlight", provide a promising, multimodal imaging tool
      for precise and accurate diagnosis and prognosis of cancers.

PMID- 28493668
TI  - Photothermal Effect Induced Negative Photoconductivity and High Responsivity in
      Flexible Black Phosphorus Transistors.
AB  - This paper reports negative photoconductivity mechanism in flexible black
      phosphorus (BP) transistors built on freestanding polyimide film. Near-infrared
      laser (lambda = 830 nm) excitation leads to significantly suppressed device on
      state current with a very high responsivity of up to 53 A/W. The underlying
      mechanism of the negative photoconductivity is attributed to the strong
      photothermal effect induced by the low thermal conductivity of the polyimide
      substrate used. The heat generated by the infrared light illumination results in
      enhanced phonon scattering, reduced carrier mobility, and consequently negative
      photocurrent. Such a phenomenon was not observed in similar BP devices built on
      SiO2/Si substrates whose thermal conductivity is much higher. The above
      photothermal mechanism is also supported by temperature-dependent electrical
      characterization and device simulation. Such a flexible BP infrared photodetector
      with ultrahigh responsivity may find potential applications in future wearable
      and biointegrated imaging systems.

PMID- 28493670
TI  - Speed up Ferroelectric Organic Transistor Memories by Using Two-Dimensional
      Molecular Crystalline Semiconductors.
AB  - Ferroelectric organic field-effect transistors (Fe-OFETs) have attracted
      intensive attention because of their promising potential in nonvolatile memory
      devices. The quick switching between binary states is a significant fundamental
      feature in evaluating Fe-OFET memories. Here, we employ 2D molecular crystals via
      a solution-based process as the conducting channels in transistor devices, in
      which ferroelectric polymer acts as the gate dielectric. A high carrier mobility
      of up to 5.6 cm2 V-1 s-1 and a high on/off ratio of 106 are obtained. In
      addition, the efficient charge injection by virtue of the ultrathin 2D molecular
      crystals is beneficial in achieving rapid operations in the Fe-OFETs; devices
      exhibit short switching time of ~2.9 and ~3.0 ms from the on- to the off-state
      and from the off- to the on-state, respectively. Consequently, the presented
      strategy is capable of speeding up Fe-OFET memory devices by using solution
      processed 2D molecular crystals.

PMID- 28493669
TI  - Amyloid-like Fibrils from an alpha-Helical Transmembrane Protein.
AB  - The propensity to misfold and self-assemble into stable aggregates is
      increasingly being recognized as a common feature of protein molecules. Our
      understanding of this phenomenon and of its links with human disease has improved
      substantially over the past two decades. Studies thus far, however, have been
      almost exclusively focused on cytosolic proteins, resulting in a lack of detailed
      information about the misfolding and aggregation of membrane proteins. As a
      consequence, although such proteins make up approximately 30% of the human
      proteome and have high propensities to aggregate, relatively little is known
      about the biophysical nature of their assemblies. To shed light on this issue, we
      have studied as a model system an archetypical representative of the ubiquitous
      major facilitator superfamily, the Escherichia coli lactose permease (LacY). By
      using a combination of established indicators of cross-beta structure and
      morphology, including the amyloid diagnostic dye thioflavin-T, circular dichroism
      spectroscopy, Fourier transform infrared spectroscopy, X-ray fiber diffraction,
      and transmission electron microscopy, we show that LacY can form amyloid-like
      fibrils under destabilizing conditions. These results indicate that transmembrane
      alpha-helical proteins, similarly to cytosolic proteins, have the ability to
      adopt this generic state.

PMID- 28493672
TI  - Correction to "Living Biomaterials".

PMID- 28493671
TI  - Cationic Polythiophenes as Gene Delivery Enhancer.
AB  - There is urgent demand of easily available and highly effective method to improve
      transgene performance of polymeric gene carriers at low consumption of delivery
      materials. We developed biocompatible multicomponent nanocomposites in which
      small quantities of cationic polythiophenes were engineered into the outer shell
      of polypeptide/DNA polyplexes without covalent linkages. We revealed the
      introduction of polythiophenes in small quantities led to multiple outcomes
      including modulation of polyplex size and zeta potential, increase in polyplex
      stability, promotion of endolysosome membrane disruption, light-induced
      generation of reactive oxygen species (ROS), and significant enhancement of gene
      delivery to tumor cells. The factors such as structural architectures, molecular
      weights, photosensitizing capability, and percentage composition of
      polythiophenes were investigated.

PMID- 28493673
TI  - Controlled Crystal Grain Growth in Mixed Cation-Halide Perovskite by Evaporated
      Solvent Vapor Recycling Method for High Efficiency Solar Cells.
AB  - We developed a new and simple solvent vapor-assisted thermal annealing (VA)
      procedure which can reduce grain boundaries in a perovskite film for fabricating
      highly efficient perovskite solar cells (PSCs). By recycling of solvent molecules
      evaporated from an as-prepared perovskite film as a VA vapor source, named the
      pot-roast VA (PR-VA) method, finely controlled and reproducible device
      fabrication was achieved for formamidinium (FA) and methylammonium (MA) mixed
      cation-halide perovskite (FAPbI3)0.85(MAPbBr3)0.15. The mixed perovskite was
      crystallized on a low-temperature prepared brookite TiO2 mesoporous scaffold.
      When exposed to very dilute solvent vapor, small grains in the perovskite film
      gradually unified into large grains, resulting in grain boundaries which were
      highly reduced and improvement of photovoltaic performance in PSC. PR-VA-treated
      large grain perovskite absorbers exhibited stable photocurrent-voltage
      performance with high fill factor and suppressed hysteresis, achieving the best
      conversion efficiency of 18.5% for a 5 * 5 mm2 device and 15.2% for a 1.0 * 1.0
      cm2 device.

PMID- 28493674
TI  - Surface Enhanced Spatially Offset Raman Spectroscopy Detection of Neurochemicals
      Through the Skull.
AB  - The ability to noninvasively detect neurotransmitters through the skull would aid
      in understanding brain function and the development of neurological diseases.
      Surface enhanced spatially offset Raman spectroscopy (SESORS) is a powerful
      technique that combines the sensitivity of surface-enhanced Raman spectroscopy
      (SERS) with the ability of spatially offset Raman spectroscopy (SORS) to probe
      subsurface layers. Here we present SERS measurements of neurotransmitters
      (melatonin, serotonin, and epinephrine) at various concentrations followed by the
      SESORS measurements of the neurotransmitters to a concentration as low as 100 MUM
      in a brain tissue mimic through a cat skull. Principal components analysis was
      performed to distinguish between the surface bone layer and the subsurface layer,
      comprised of a brain tissue mimic modified with neurotransmitters, and to
      determine if each individual neurotransmitter could be accurately identified.

PMID- 28493675
TI  - Investigation of Thermal Stability of P2-NaxCoO2 Cathode Materials for Sodium Ion
      Batteries Using Real-Time Electron Microscopy.
AB  - Here, we take advantage of in situ transmission electron microscopy (TEM) to
      investigate the thermal stability of P2-type NaxCoO2 cathode materials for sodium
      ion batteries, which are promising candidates for next-generation lithium ion
      batteries. A double-tilt TEM heating holder was used to directly characterize the
      changes in the morphology and the crystallographic and electronic structures of
      the materials with increase in temperature. The electron diffraction patterns and
      the electron energy loss spectra demonstrated the presence of cobalt oxides
      (Co3O4, CoO) and even metallic cobalt (Co) at higher temperatures as a result of
      reduction of Co ions and loss of oxygen. The bright-field TEM images revealed
      that the surface of NaxCoO2 becomes porous at high temperatures. Higher cutoff
      voltages result in degrading thermal stability of NaxCoO2. The observations
      herein provide a valuable insight that thermal stability is one of the important
      factors to be considered in addition to the electrochemical properties when
      developing new electrode materials for novel battery systems.

PMID- 28493676
TI  - Skin Sensitization QMM for HRIPT NOEL Data: Aldehyde Schiff-Base Domain.
AB  - The general chemistry principles underlying skin sensitization for Schiff base
      (SB) electrophiles may be used to develop a quantitative mechanistic model (QMM),
      based on reactivity supplemented with a hydrophobicity parameter for some but not
      all structures within the SB reaction domain. For aliphatic Schiff base
      electrophiles, the log of the no observed effect level (NOEL) values (pNOEL) from
      the human repeated insult patch test (HRIPT) can be calculated by the reactivity
      parameter summation of sigma star values (Sigmasigma*) and a hydrophobicity
      parameter (logP). Specifically, the QMM, pNOEL = 2.34(+/-0.33) Sigmasigma* +
      0.19(+/-0.07) logP - 2.62(+/-0.22), n = 19, R2 = 0.77, R2(adj) = 0.74, s = 0.20,
      F = 27, was developed. Not all parts of the Schiff base domain are modeled with
      one equation. Particularly, predicting aromatic aldehydes and ketones appears to
      require a separate equation. Interestingly, the same physical organic chemical
      properties originally applied to modeling the local lymph node assay potency of
      Schiff base electrophiles apply to human potency as represented by the HRIPT.

PMID- 28493677
TI  - The N6-Position of Adenine Is a Blind Spot for TAL-Effectors That Enables
      Effective Binding of Methylated and Fluorophore-Labeled DNA.
AB  - Transcription-activator-like effectors (TALEs) are programmable DNA binding
      proteins widely used for genome targeting. TALEs consist of multiple concatenated
      repeats, each selectively recognizing one nucleobase via a defined repeat
      variable diresidue (RVD). Effective use of TALEs requires knowledge about their
      binding ability to epigenetic and other modified nucleobases occurring in target
      DNA. However, aside from epigenetic cytosine-5 modifications, the binding ability
      of TALEs to modified DNA is unknown. We here study the binding of TALEs to the
      epigenetic nucleobase N6-methyladenine (6mA) found in prokaryotic and recently
      also eukaryotic genomes. We find that the natural, adenine (A)-binding RVD NI is
      insensitive to 6mA. Model-assisted structure-function studies reveal
      accommodation of 6mA by RVDs with altered hydrophobic surfaces and abilities of
      hydrogen bonding to the N6-amino group or N7 atom of A. Surprisingly, this
      tolerance of N6 substitution was transferrable to bulky N6-alkynyl substituents
      usable for click chemistry and even to a large rhodamine dye, establishing the N6
      position of A as the first site of DNA that offers label introduction within TALE
      target sites without interference. These findings will guide future in vivo
      studies with TALEs and expand their applicability as DNA capture probes for
      analytical applications in vitro.

PMID- 28493678
TI  - Deciphering the Structural Relationships of Five Cd-Based Metal-Organic
      Frameworks.
AB  - The one-pot reaction of Cd(NO3)2.4H2O and 5-(6-(hydroxymethyl)pyridin-3
      yl)isophthalic acid (H2L) in DMF/H2O (DMF = N,N-dimethylformamide) produced a two
      dimensional (2D) metal-organic framework (MOF) of [Cd(L)(H2O)2] (A) bearing aqua
      bridged Cd centers, accompanied by two three-dimensional (3D) MOFs
      [Cd(L)(DMF)0.5] (B) and [Cd(L)] (C). Removing the bridging aqua molecules of A by
      heating led to the formation of an additional 3D MOF of [Cd(L)] (D) in a single
      crystal to single-crystal (SCSC) manner. The search for the preceding compound
      that could convert to A resulted in the isolation of a 2D MOF [Cd(L)(DMF)] (E)
      that readily converted to A in water, but with the loss of single crystallinity.
      Upon excitation at 350 nm, A, D, E, and the ligand H2L fluoresced at 460 nm, 468
      nm, 475 nm, and 411 nm, respectively. The fluorescence of A could be used for the
      selective detection of Fe3+ in water down to 0.58 ppm. This quenching was not
      affected by the presence of other common metal ions.

PMID- 28493679
TI  - Light-Induced Fluorescence Modulation of Quantum Dot-Crystal Violet Conjugates:
      Stochastic Off-On-Off Cycles for Multicolor Patterning and Super-Resolution.
AB  - Photoswitching or modulation of quantum dots (QDs) can be promising for many
      fields that include display, memory, and super-resolution imaging. However, such
      modulations have mostly relied on photomodulations of conjugated molecules in QD
      vicinity, which typically require high power of high energy photons at UV. We
      report a visible light-induced facile modulation route for QD-dye conjugates. QD
      crystal violets conjugates (QD-CVs) were prepared and the crystal violet (CV)
      molecules on QD quenched the fluorescence efficiently. The fluorescence of QD-CVs
      showed a single cycle of emission burst as they go through three stages of (i)
      initially quenched "off" to (ii) photoactivated "on" as the result of chemical
      change of CVs induced by photoelectrons from QD and (iii) back to photodarkened
      "off" by radical-associated reactions. Multicolor on-demand photopatterning was
      demonstrated using QD-CV solid films. QD-CVs were introduced into cells, and
      excitation with visible light yielded photomodulation from "off" to "on" and
      "off" by nearly ten fold. Individual photoluminescence dynamics of QD-CVs was
      investigated using fluorescence correlation spectroscopy and single QD emission
      analysis, which revealed temporally stochastic photoactivations and
      photodarkenings. Exploiting the stochastic fluorescence burst of QD-CVs,
      simultaneous multicolor super-resolution localizations were demonstrated.

PMID- 28493680
TI  - Legacy and Current-Use Insecticides in Agricultural Sediments from South China:
      Impact of Application Pattern on Occurrence and Risk.
AB  - Legacy and current-use insecticides were analyzed in sediments collected from a
      typical rice-planting region in South China. Total concentrations of insecticides
      varied from 1.63 to 775 ng g-1 with mean and median values of 67.0 and 11.5 ng g
      1, respectively. Pyrethroids predominated pesticide composition (31.7%), followed
      by organophosphates (23.0%) and fiproles (20.8%). Sediment risk analysis showed
      that pyrethroids, fiproles, and abamectin posed significant risk to benthic
      invertebrates in one-third of sediments. Different distributions of pyrethroids
      and organophosphates in urban and agricultural areas were consistent with their
      application patterns, whereas legacy organochlorine pesticides showed no region
      specific distribution because of rapid transition of land use pattern from
      agricultural to urban areas. Likely illegal use of pyrethroids and fipronil
      caused serious ecological risks in agricultural waterways. Pyrethroids and
      fipronil were restricted to use in paddy fields, but their occurrence and risk in
      agricultural waterways were high, calling for better measures to regulate the
      illegal use of insecticides.

PMID- 28493681
TI  - Self-Assembled Molecular Hybrids of CoS-DNA for Enhanced Water Oxidation with Low
      Cobalt Content.
AB  - Water oxidation in alkaline medium was efficiently catalyzed by the self
      assembled molecular hybrids of CoS-DNA that had 20 times lower Co loading than
      the commonly used loading. The morphological outcome was directed by varying the
      molar ratio of metal precursor Co(Ac)2 and DNA and three different sets of CoS
      DNA molecular hybrids, viz. CoS-DNA(0.036), CoS-DNA(0.06), and CoS-DNA(0.084)
      were prepared. These morphologically distinct hybrids had shown similar
      electrocatalytic behavior, because of the fact that they all contained the same
      cobalt content. The CoS-DNA(0.036), CoS-DNA(0.06), and CoS-DNA(0.084) required
      very low overpotentials of 350, 364, and 373 mV at a current density of 10 mA cm
      2 (1 M KOH), respectively. The advantages of lower overpotential, lower Tafel
      slope (42.7 mV dec-1), high Faradaic efficiency (90.28%), high stability and
      reproducibility after all, with a lower cobalt loading, have certainly shown the
      worth of these molecular hybrids in large-scale water oxidation. Moreover, since
      DNA itself a good binder, CoS-DNA molecular hybrids were directly casted on
      substrate electrodes and used after drying. It also showed minimum intrinsic
      resistance as DNA is a good ionic and electronic conductor. Besides, the present
      method may also be extended for the preparation of other active electrocatalysts
      for water splitting.

PMID- 28493682
TI  - A New Split Charge Equilibration Model and REPEAT Electrostatic Potential Fitted
      Charges for Periodic Frameworks with a Net Charge.
AB  - Periodic frameworks that possess a net charge, such as zeolites, are an important
      class of materials in wide use. For guest-host interactions to be simulated in
      these materials, partial atomic charges are often used. In this work, we
      investigate two methods for the generation of partial atomic charges in periodic
      systems having a net framework charge. We first examine the validity of
      generating REPEAT electrostatic potential fitted charges derived from periodic
      electronic structure calculations, where a constant background charge is added to
      neutralize the net charge on the framework. The constant background charge
      obviates the need to add neutralizing counterions, which may induce artifacts
      such as polarization in the infinite periodic system. The second method we
      explore is the split charge equilibration (SQE) method for the rapid generation
      of partial atomic charges. The original formulation of the SQE method cannot be
      applied to systems with a net charge. In this work, we reformulate the SQE method
      by transforming the split charges into an atomic charge basis that allows for non
      neutral systems to be treated. The new SQE model, which we call SQEAB (for atomic
      basis), was validated with a series of tests using both charged and neutral metal
      organic frameworks and zeolites. It was shown that SQEAB gives equivalent results
      to those of the original SQE model for neutral systems. We then demonstrated that
      the SQEAB method is able to "capture" the chemical structure of a charged
      framework better than that of the charge equilibration model by comparing to
      REPEAT electrostatic potential fitted charges.

PMID- 28493683
TI  - Plant Uptake and Metabolism of Nitrofuran Antibiotics in Spring Onion Grown in
      Nitrofuran-Contaminated Soil.
AB  - Environmental pollution caused by the discharge of mutagenic and carcinogenic
      nitrofurans to the aquatic and soil environment is an emerging public health
      concern because of the potential in producing drug-resistant microbes and being
      uptaken by food crops. Using liquid chromatography-tandem mass spectrometry
      analysis and with spring onion (Allium wakegi Araki) as the plant model, we
      investigated in this study the plant uptake and accumulation of nitrofuran from a
      contaminated environment. Our study revealed for the first time high uptake and
      accumulation rates of nitrofuran in the edible parts of the food crop.
      Furthermore, results indicated highly efficient plant metabolism of the absorbed
      nitrofuran within the plant, leading to the formation of genotoxic hydrazine
      containing metabolites. The results from this study may disclose a previously
      unidentified human exposure pathway through contaminated food crops.

PMID- 28493684
TI  - What Makes a Density Functional Approximation Good? Insights from the Left Fukui
      Function.
AB  - This work proposes, justifies, and reports tests of the chemically relevant left
      Fukui function of Li, C, and F on a range of density functional approximations.
      Analysis indicates that functionals can be good at densities and bad at Fukui
      functions, and vice versa, analogous with energies and ionization potentials.
      "TPSSh", "SOGGA11X", and "B2PLYP" are star performers on both, however. Many
      "Minnesota functionals" fare much better here than in a recent analysis of
      electron densities. In this context, new optimizing strategies are mentioned.

PMID- 28493686
TI  - First Do No Harm: The Need to Explore Potential Adverse Health Implications of
      Drinking Rainwater.

PMID- 28493685
TI  - Selective Detection of Shiga-like Toxin 1 from Complex Samples Using Pigeon
      Ovalbumin Functionalized Gold Nanoparticles as Affinity Probes.
AB  - Escherichia coli O157:H7 is a foodborne pathogen. This bacterial strain can
      generate Shiga-like toxins (SLTs), which can cause serious sickness and even
      death. Thus, it is important to develop effective and sensitive methods that can
      be used to rapidly identify the presence of SLTs from complex samples. Pigeon egg
      white (PEW) contains abundant glycoproteins, including pigeon ovalbumin (POA)
      (~60%). POA possesses Gal-alpha(1->4)-Gal-beta(1->4)-GlcNAc termini, which can
      recognize the B subunits in SLT type 1 (SLT-1B). Thus, POA is a suitable probe
      for trapping SLT-1B. In this work, we used PEW proteins as starting materials to
      react with aqueous tetrachloroauric acid for generation of PEW-protein
      immobilized gold nanoparticles (AuNPs@PEW) via one-pot reactions. We demonstrated
      that the generated AuNPs@PEW were mainly dominated by POA-immobilized Au NPs. The
      as-prepared AuNPs@PEW were used as affinity probes to selectively probe SLT-1B
      from complex cell lysates derived from E. coli O157:H7. The selective trapping
      step can be completed within ~90 s under microwave heating (power = 450 W) to
      enrich sufficient SLT-1B for matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometric analysis. Furthermore, this approach can be used to detect SLT
      1B at a concentration as low as ~40 pM. The feasibility of using the proposed
      method to selectively detect SLT-1B from ham contaminated by E. coli O157:H7 was
      also demonstrated.

PMID- 28493687
TI  - Comparative Metabolic Response between Cucumber ( Cucumis sativus) and Corn ( Zea
      mays) to a Cu(OH)2 Nanopesticide.
AB  - Due to their unique properties, copper-based nanopesticides are emerging in the
      market. Thus, understanding their effect on crop plants is very important.
      Metabolomics can capture a snapshot of cellular metabolic responses to a
      stressor. We selected maize and cucumber as model plants for exposure to
      different doses of Cu(OH)2 nanopesticide. GC-TOF-MS-based metabolomics was
      employed to determine the metabolic responses of these two species. Results
      revealed significant differences in metabolite profile changes between maize and
      cucumber. Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming
      in both species, but in different manners. In maize, several intermediate
      metabolites of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up
      regulated, indicating the energy metabolism was activated. In addition, the
      levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and
      their precursors (phenylalanine, tyrosine) were enhanced, indicating the
      activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an
      antioxidant defense-related pathway. In cucumber, arginine and proline metabolic
      pathways were the most significantly altered pathway. Both species exhibited
      altered levels of fatty acids and polysaccharides, suggesting the cell membrane
      and cell wall composition may change in response to Cu(OH)2 nanopesticide. Thus,
      metabolomics helps to deeply understand the differential response of these plants
      to the same nanopesticide stressor.

PMID- 28493688
TI  - Isolation and Characterization of a Human Intestinal Bacterium Eggerthella sp.
      AUH-JLD49s for the Conversion of (-)-3'-Desmethylarctigenin.
AB  - Arctiin is the most abundant bioactive compound contained in the Arctium lappa
      plant. In our previous study, we isolated one single bacterium capable of
      bioconverting arctigenin, an aglycone of arctiin, to 3'-desmethylarctigenin (3'
      DMAG) solely. However, to date, a specific bacterium capable of producing other
      arctiin metabolites has not been reported. In this study, we isolated one single
      bacterium, which we named Eggerthella sp. AUH-JLD49s, capable of bioconverting 3'
      DMAG under anaerobic conditions. The metabolite of 3'-DMAG by strain AUH-JLD49s
      was identified as 3'-desmethyl-4'-dehydroxyarctigenin (DMDH-AG) based on
      electrospray ionization mass spectrometry (ESI-MS) and 1H and 13C nuclear
      magnetic resonance spectroscopy. The bioconversion kinetics and bioconversion
      capacity of strain AUH-JLD49s were investigated. In addition, the metabolite DMDH
      AG showed an inhibitory effect on cell growth of human colon cancer cell line
      HCT116 and human breast cancer cell line MDA-MB-231.

PMID- 28493690
TI  - Chemically Propelled Molecules and Machines.
AB  - Self-propelled, synthetic active matters that transduce chemical energy into
      mechanical motion are examples of biomimetic nonequilibrium systems. They are of
      great current interest, with potential applications in nanomachinery, nanoscale
      assembly, fluidics, and chemical/biochemical sensing. Many of the physical
      challenges associated with generating motility on the micro- and nanoscale have
      recently been overcome, leading to the first generation of autonomous motors and
      pumps on scales ranging from microns to nanometers. This perspective focuses on
      catalytically powered motile systems, outlining major advances to date in
      motor/pump design, propulsion mechanisms and directional control, and intermotor
      communications leading to collective behavior. We conclude by discussing the
      possible future directions, from the fundamental questions that remain to be
      addressed to the design principles required for useful applications.

PMID- 28493689
TI  - A Bis-calix[4]pyrrole Enzyme Mimic That Constrains Two Oxoanions in Close
      Proximity.
AB  - Herein we describe a large capsule-like bis-calix[4]pyrrole 1, which is able to
      host concurrently two dihydrogen phosphate anions within a relatively large
      internal cavity. Evidence for the concurrent, dual recognition of the
      encapsulated anions came from 1H NMR and UV-vis spectroscopies and ITC titrations
      carried out in CD2Cl2/CD3OD (9/1, v/v) or dichloroethane (DCE), as well as single
      crystal X-ray diffraction analyses. Receptor 1 was also found to bind two
      dianionic sulfate anions bridged by two water molecules in the solid state. The
      resulting sulfate dimer was retained in DCE solution, as evidenced by
      spectroscopic analyses. Finally, receptor 1 was found capable of accommodating
      two trianionic pyrophosphate anions in the cavity. The present experimental
      findings are supported by DFT calculations along with 1H NMR and UV-vis
      spectroscopies, ITC studies, and single crystal X-ray diffraction analyses.

PMID- 28493691
TI  - Surface Proton Transfer Promotes Four-Electron Oxygen Reduction on Gold
      Nanocrystal Surfaces in Alkaline Solution.
AB  - Four-electron oxygen reduction reaction (4e-ORR), a key pathway in energy
      conversion, is preferred over the two-electron reduction pathway that falls short
      in dissociating dioxygen molecules. Gold surfaces exhibit high sensitivity of the
      ORR pathway to its atomic structures. A long-standing puzzle remains unsolved:
      why the Au surfaces with {100} sub-facets were exceptionally capable to catalyze
      the 4e-ORR in alkaline solution, though limited within a narrow potential window.
      Herein we report the discovery of a dominant 4e-ORR over the whole potential
      range on {310} surface of Au nanocrystal shaped as truncated ditetragonal prism
      (TDP). In contrast, ORR pathways on single-crystalline facets of shaped
      nanoparticles, including {111} on nano-octahedra and {100} on nanocubes, are
      similar to their single-crystal counterparts. Combining our experimental results
      with density functional theory calculations, we elucidate the key role of surface
      proton transfers from co-adsorbed H2O molecules in activating the facet- and
      potential-dependent 4e-ORR on Au in alkaline solutions. These results elucidate
      how surface atomic structures determine the reaction pathways via bond scission
      and formation among weakly adsorbed water and reaction intermediates. The new
      insight helps in developing facet-specific nanocatalysts for various reactions.

PMID- 28493692
TI  - Uptake Kinetics and Subcellular Compartmentalization Explain Lethal but Not
      Sublethal Effects of Cadmium in Two Closely Related Amphipod Species.
AB  - Eulimnogammarus cyaneus and Eulimnogammarus verrucosus, closely related amphipod
      species endemic to Lake Baikal, differ with respect to body size (10- to 50-fold
      lower fresh weights of E. cyaneus) and cellular stress response (CSR) capacity,
      potentially causing species-related differences in uptake, internal
      sequestration, and toxic sensitivity to waterborne cadmium (Cd). We found that,
      compared to E. verrucosus, Cd uptake rates, related to a given exposure
      concentration, were higher, and lethal concentrations (50%; LC50) were 2.3-fold
      lower in E. cyaneus (4 weeks exposure; 6  degrees C). Upon exposures to species
      specific subacutely toxic Cd concentrations (nominal LC1; E. cyaneus: 18 nM (2.0
      MUg L-1); E. verrucosus: 115 nM (12.9 MUg L-1); 4 weeks exposure; 6  degrees C),
      Cd amounts in metal sensitive tissue fractions (MSF), in relation to fresh
      weight, were similar in both species (E. cyaneus: 0.25 +/- 0.06 MUg g-1; E.
      verrucosus: 0.26 +/- 0.07 MUg g-1), whereas relative Cd amounts in the
      biologically detoxified heat stable protein fraction were 35% higher in E.
      cyaneus. Despite different potencies in detoxifying Cd, body size appears to
      mainly explain species-related differences in Cd uptake and sensitivities. When
      exposed to Cd at LC1 over 4 weeks, only E. verrucosus continuously showed 15-36%
      reduced oxygen consumption rates indicating metabolic depression and pointing to
      particular sensitivity of E. verrucosus to persisting low-level toxicant
      pressure.

PMID- 28493693
TI  - Development of Lennard-Jones and Buckingham Potentials for Lanthanoid Ions in
      Water.
AB  - New sets of Lennard-Jones and Buckingham potentials have been developed to be
      used in classical molecular dynamics simulations of Ln3+-containing systems for
      the whole lanthanoid series. The force-field parameters have been refined by
      directly comparing the hydration structure obtained from the simulations with the
      extended X-ray absorption fine structure (EXAFS) experimental data, in order to
      reproduce Ln3+-water EXAFS experimentally inferred mean distances. Analysis of
      the simulation results has shown that both Lennard-Jones and Buckingham
      potentials are able to properly describe the radial distribution of water
      molecules around the Ln3+ ions, the smooth decrease of the hydration number along
      the lanthanoid series, as well as the geometry of the first-shell hydration
      complex formed by Ln3+ ions in water. The newly optimized interaction potential
      parameters can be used in conjunction with force fields available in the
      literature to investigate the solvation properties of Ln3+ ions in different
      disordered systems.

PMID- 28493694
TI  - Community Vulnerability to Health Impacts of Wildland Fire Smoke Exposure.
AB  - Identifying communities vulnerable to adverse health effects from exposure to
      wildfire smoke may help prepare responses, increase the resilience to smoke and
      improve public health outcomes during smoke days. We developed a Community Health
      Vulnerability Index (CHVI) based on factors known to increase the risks of health
      effects from air pollution and wildfire smoke exposures. These factors included
      county prevalence rates for asthma in children and adults, chronic obstructive
      pulmonary disease, hypertension, diabetes, obesity, percent of population 65
      years of age and older, and indicators of socioeconomic status including poverty,
      education, income and unemployment. Using air quality simulated for the period
      between 2008 and 2012 over the continental U.S. we also characterized the
      population size at risk with respect to the level and duration of exposure to
      fire-originated fine particulate matter (fire-PM2.5) and CHVI. We estimate that
      10% of the population (30.5 million) lived in the areas where the contribution of
      fire-PM2.5 to annual average ambient PM2.5 was high (>1.5 MUg/m3) and that 10.3
      million individuals experienced unhealthy air quality levels for more than 10
      days due to smoke. Using CHVI we identified the most vulnerable counties and
      determined that these communities experience more smoke exposures in comparison
      to less vulnerable communities.

PMID- 28493695
TI  - Unexpected Observation of the Dimroth Rearrangement in the Ribosylation of 4
      Aminopyrimidines.
AB  - A method for the preparation of 1-(N-ribofuranosyl)-6-imino-1,6-dihydropyrimidin
      4-amines 3 or 4-(N-ribofuranosyl)-6-aminopyrimidines 4 via glycosylation of 4
      aminopyrimidines 2 or 5 is described. Silylated 4-aminopyrimidines 2 or 5 upon
      ribosylation with 1 provide products 3. When intermediates 3 contain a strongly
      electron-withdrawing group, such as C(4)-Cl or C(5)-NO2, they rearrange to
      products 4 in the presence of aqueous ammonia. A mechanism is proposed that
      involves a ring-opening/ring-closing (Dimroth) rearrangement.

PMID- 28493696
TI  - Impact of Conjugation and Hyperconjugation on the Radical Stability of Allylic
      and Benzylic Systems: A Theoretical Study.
AB  - Resonantly stabilized radicals are some of the most investigated chemical species
      due to their preferential formation in a wide variety of chemical environments.
      Density functional theory and post-Hartree-Fock calculations were utilized to
      elucidate the chemical interactions that contribute to the stability of two
      ubiquitous, resonantly stabilized radicals, allyl and benzyl radicals. The
      relative stability of these radical species was quantified through bond
      dissociation energies and relative rotational energy barriers, with a difference
      of only 0.1 kcal/mol. To clarify and contextualize the energetic results, natural
      bond orbitals were used to evaluate the atomic spin density distribution in the
      given molecules. The benzyl radical was found to be ~3 kcal/mol less stable than
      the allyl radical, which was attributed to the inability to efficiently
      delocalize the spin on a phenyl unit, starkly contrary to general chemistry
      knowledge. Increasing the degree of pi-conjugation and hyperconjugation was shown
      to benefit allyl radicals to a greater degree than benzyl radicals, again due to
      more efficient radical delocalization in allyl radicals. This work highlights
      that more resonance structures do not always lead to a more stabilized radical
      species, and provides fundamental knowledge about how conjugation and
      hyperconjugation impact the stabilization of nonbonding electrons in these
      systems.

PMID- 28493697
TI  - Molecular Explanation for the Abnormal Flux of Material into a Hot Spot in Ester
      Monolayers.
AB  - Langmuir monolayers of certain surfactants show a negative derivative of the
      surface pressure with respect to temperature. In these monolayers, a local
      temperature gradient leads to local yielding of the solid phase to a kinetically
      flowing liquid, so that the material flows toward the hotter regions that act as
      sinks. The accumulation of material leads to the formation of nonequilibrium
      multilamellar bubbles of different sizes. Here we investigate the molecular
      factors leading to such a peculiar behavior. First, we identify the required
      structural molecular moieties, and second we vary the composition of the subphase
      in order to analyze its influence. We conclude that esters appear to be unique in
      two key aspects: they form monolayers whose compression isotherms shift to lower
      areas as the temperature increases, and thus collapse into a hot spot; and they
      bind weakly to the aqueous subphase, i.e., water does not attach to the monolayer
      at the molecular level, but only supports it. Molecular simulations for a
      selected system confirm and help explain the observed behavior: surfactant
      molecules form a weak hydrogen bonding network, which is disrupted upon heating,
      and also the molecular tilting changes with temperature, leading to changes in
      the film density.

PMID- 28493699
TI  - Electrochemical Oxidation of Phenolic Compounds at Boron-Doped Diamond Anodes:
      Structure-Reactivity Relationships.
AB  - Electrochemical oxidation of phenolic compounds using boron-doped diamond (BDD)
      anodes has been shown as an effective approach to remove these contaminants from
      water. However, the understanding of the reaction mechanisms of substituted
      phenolic compounds at the BDD anode remains incomplete. In the present work, we
      investigated the electrochemical oxidation of 12 representative phenolic
      compounds (with varied substitution groups (e.g., -CH3, -OCH3, -NH2, -Cl, -OH, 
      COOH, -NO2, -CHO) and positions (-ortho, -meta, and -para)) at the BDD anode. Our
      analysis shows that unlike previous studies the two parameters, the Hammett
      constants of the substituents and the highest atomic charge on the aromatic ring,
      fail to adequately describe the reaction rate change when the chemical structures
      become complicated (i.e., with increased steric effects). Instead, a quantitative
      structure-property relationship (QSPR) was established with 26 molecular
      descriptors and using a partial least-squares regression approach. The QSPR
      analysis shows that the energy gap between the lowest unoccupied molecular
      orbital and the highest occupied molecular orbital, ELUMO - EHOMO, which reflects
      the chemical stability of a molecule, is the predominant molecular descriptor
      determining the reaction rate constant. Furthermore, the predicated rate
      constants agree well with the observed ones. The findings are consistent with
      previous studies of SnO2 anodes, suggesting that chemical structural parameters
      such as the molecular orbital energies are critical to consider when elucidating
      and predicating the electrochemical reactivity of phenolic compounds at these
      nonactive anodes.

PMID- 28493700
TI  - Effect of Fluorination on the Competition of Halogen Bonding and Hydrogen
      Bonding: Complexes of Fluoroiodomethane with Dimethyl Ether and Trimethylamine.
AB  - To further rationalize the competition between halogen and hydrogen bonding, a
      combined experimental and theoretical study on the weakly bound molecular
      complexes formed between the combined halogen bond/hydrogen bond donor
      fluoroiodomethane and the Lewis bases dimethyl ether and trimethylamine (in
      standard and fully deuterated form) is presented. The experimental data are
      obtained by recording infrared and Raman spectra of mixtures of the compounds in
      liquid krypton, at temperatures between 120 and 156 K. The experiments are
      supported by ab initio calculations at the MP2/aug-cc-pVDZ-PP level, statistical
      thermodynamics and Monte Carlo free energy perturbation calculations. For the
      mixtures containing fluoroiodomethane and dimethyl ether a hydrogen-bonded
      complex with an experimental complexation enthalpy of -7.0(2) kJ mol-1 is
      identified. Only a single weak spectral feature is observed which can be
      tentatively assigned to the halogen-bonded complex. For the mixtures involving
      trimethylamine, both halogen- and hydrogen-bonded complexes are observed, the
      experimental complexation enthalpies being -12.5(1) and -9.6(2) kJ mol-1
      respectively. To evaluate the influence of fluorination on the competition
      between halogen and hydrogen bonding, the results obtained for fluoroiodomethane
      are compared with those of a previous study involving difluoroiodomethane.

PMID- 28493698
TI  - 4-Methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridine-Based P2X7 Receptor Antagonists:
      Optimization of Pharmacokinetic Properties Leading to the Identification of a
      Clinical Candidate.
AB  - The synthesis and preclinical characterization of novel 4-(R)-methyl-6,7-dihydro
      4H-triazolo[4,5-c]pyridines that are potent and selective brain penetrant P2X7
      antagonists are described. Optimization efforts based on previously disclosed
      unsubstituted 6,7-dihydro-4H-triazolo[4,5-c]pyridines, methyl substituted 5,6,7,8
      tetrahydro[1,2,4]triazolo[4,3-a]pyrazines, and several other series lead to the
      identification of a series of 4-(R)-methyl-6,7-dihydro-4H-triazolo[4,5
      c]pyridines that are selective P2X7 antagonists with potency at the rodent and
      human P2X7 ion channels. These novel P2X7 antagonists have suitable
      physicochemical properties, and several analogs have an excellent pharmacokinetic
      profile, good partitioning into the CNS and show robust in vivo target engagement
      after oral dosing. Improvements in metabolic stability led to the identification
      of JNJ-54175446 (14) as a candidate for clinical development. The drug discovery
      efforts and strategies that resulted in the identification of the clinical
      candidate are described herein.

PMID- 28493702
TI  - Copper-Catalyzed Functionalizations of C60 with Amino Alcohols.
AB  - CuI-catalyzed diverse functionalizations of C60 with amino alcohols with aerobic
      oxygen as the sole oxidant have been explored. For 2-/3-amino alcohols, an
      aminooxygenation reaction occurs to generate fulleromorpholine and
      fullerooxazepane derivatives. When a tethered furan ring exists, a further
      intramolecular [4 + 2] reaction with the neighboring double bond occurs to
      furnish the cis-1 products. In the case of 4-/5-amino alcohols, methanofullerenes
      linking with cyclic amides are obtained through cyclic enamine intermediates.

PMID- 28493703
TI  - Theoretical Study of the BF3-Promoted Rearrangement of Oxiranyl N
      Methyliminodiacetic Acid Boronates.
AB  - The mechanism of the rearrangement of oxiranyl N-methyliminodiacetyl (MIDA)
      boronates in dicholoromethane has been extensively investigated with density
      functional theory. Several reaction pathways were examined. Our results revealed
      that the most-favorable mechanisms for the BF3-promoted rearrangement of 2-phenyl
      oxiranyl MIDA boronate (1) and 1-phenyl oxiranyl MIDA boronate (24) comprise two
      steps: ring opening of the epoxide to a carbocation intermediate followed by
      migration of a MIDA-boryl group (for the reaction of 1) and hydrogen (for the
      reaction of 24), to give the same BF3-coordinated alpha-boryl aldehyde in both
      cases. The first step of the ring opening of the epoxide is the rate-determining
      step of these reactions. In the rearrangement step for the reaction of 1, the
      MIDA-boryl group migrates easily, probably because of its electron-rich sp3
      hybridized boron center. For 24, the most-favorable pathway involves a rare boryl
      substituted carbocation. The course of these reactions is mainly controlled by
      electronic effects, although steric effects are also significant. The higher
      energy barrier calculated for the unsubstituted oxiranyl MIDA boronate (31)
      explains the lack of reactivity in the studied BF3-promoted rearrangement.

PMID- 28493701
TI  - Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as
      Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A
      (TMEM16A).
AB  - Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium
      activated chloride channel expressed widely mammalian cells, including epithelia,
      vascular smooth muscle tissue, electrically excitable cells, and some tumors.
      TMEM16A inhibitors have been proposed for treatment of disorders of epithelial
      fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we
      report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3
      carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48
      synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure
      activity studies indicated the importance of benzene substituted as 2- or 4
      methyl, or 4-fluoro, and defined the significance of thiophene substituents and
      size of the cycloalkylthiophene core. The most potent compound (10bm), which
      contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC50
      of ~30 nM, ~3.6-fold more potent than the most potent previously reported TMEM16A
      inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and
      reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp
      analysis. AACTs may be useful as pharmacological tools to study TMEM16A function
      and as potential drug development candidates.

PMID- 28493704
TI  - Chemoselective Reduction of Azlactones Using Schwartz's Reagent.
AB  - Highly chemoselective addition of Schwartz's reagent to widely available
      azlactones is described. This method allows the preparation of challenged
      functionalized alpha-amino aldehydes, in good to high isolated yields at room
      temperature, after only 2 min reaction. The presence of sensitive functionalities
      or electronic factors does not compromise the potential of the method. The use of
      an excess of the reducing reagent gave a very functionalized allylic alcohol
      derivative in 86% yield.

PMID- 28493706
TI  - Correction to Multilayered Modeling of Particulate Matter Removal by a Growing
      Forest over Time, From Plant Surface Deposition to Washoff via Rainfall.

PMID- 28493707
TI  - General Physical Description of the Behavior of Oppositely Charged
      Polyelectrolyte/Surfactant Mixtures at the Air/Water Interface.
AB  - This work reports a unifying general physical description of the behavior of
      oppositely charged polyelectrolyte/surfactant mixtures at the air/water interface
      in terms of equilibrium vs nonequilibrium extremes. The
      poly(diallyldimethylammonium chloride)/sodium dodecyl sulfate system with added
      NaCl at two different bulk polyelectrolyte concentrations and the poly(sodium
      styrenesulfonate)/dodecyltrimethylammonium bromide system have been
      systematically examined using a variety of bulk and surface techniques.
      Similarities in the general behavior are observed for all the investigated
      systems. Following the slow precipitation of aggregates in the equilibrium two
      phase region, which can take several days or even weeks, depletion of surface
      active material can result in a surface tension peak. The limiting time scale in
      the equilibration of the samples is discussed in terms of a balance between those
      of aggregate growth and settling. Bulk aggregates may spontaneously dissociate
      and spread material in the form of a kinetically trapped film if they interact
      with the interface, and a low surface tension then results out of equilibrium
      conditions. These interactions can occur prior to bulk equilibration while there
      remains a suspension of aggregates that can diffuse to the interface and
      following bulk equilibration if the settled precipitate is disturbed. Two clear
      differences in the behavior of the systems are the position in the isotherm of
      the surface tension peak and the time it takes to evolve. These features are both
      rationalized in terms of the nature of the bulk binding interactions.

PMID- 28493705
TI  - Quantification of Hemoglobin and White Blood Cell DNA Adducts of the Tobacco
      Carcinogens 2-Amino-9H-pyrido[2,3-b]indole and 4-Aminobiphenyl Formed in Humans
      by Nanoflow Liquid Chromatography/Ion Trap Multistage Mass Spectrometry.
AB  - Aromatic amines covalently bound to hemoglobin (Hb) as sulfinamide adducts at the
      cysteine 93 residue of the Hb beta chain have served as biomarkers to assess
      exposure to this class of human carcinogens for the past 30 years. In this study,
      we report that 2-amino-9H-pyrido[2,3-b]indole (AalphaC), an abundant carcinogenic
      heterocyclic aromatic amine formed in tobacco smoke and charred cooked meats,
      also reacts with Hb to form a sulfinamide adduct. A novel nanoflow liquid
      chromatography/ion trap multistage mass spectrometry (nanoLC-IT/MS3) method was
      established to assess exposure to AalphaC and the tobacco-associated bladder
      carcinogen 4-aminobiphenyl (4-ABP) through their Hb sulfinamide adducts.
      Following mild acid hydrolysis of Hb in vitro, the liberated AalphaC and 4-ABP
      were derivatized with acetic anhydride to form the N-acetylated amines, which
      were measured by nanoLC-IT/MS3. The limits of quantification (LOQ) for AalphaC-
      and 4-ABP-Hb sulfinamide adducts were <=7.1 pg/g Hb. In a pilot study, the mean
      level of Hb sulfinamide adducts of AalphaC and 4-ABP were, respectively, 3.4-fold
      and 4.8-fold higher in smokers (>20 cigarettes/day) than nonsmokers. In contrast,
      the major DNA adducts of 4-ABP, N-(2'-deoxyguanosin-8-yl)-4-aminobiphenyl, and
      AalphaC, N-(2'-deoxyguanosin-8-yl)-2-amino-9H-pyrido[2,3-b]indole, were below the
      LOQ (3 adducts per 109 bases) in white blood cell (WBC) DNA of smokers and
      nonsmokers. These findings reaffirm that tobacco smoke is a major source of
      exposure to AalphaC. Hb sulfinamide adducts are suitable biomarkers to biomonitor
      4-ABP and AalphaC; however, neither carcinogen binds to DNA in WBC, even in heavy
      smokers, at levels sufficient for biomonitoring.

PMID- 28493708
TI  - Discrimination of Diverse Coherences Allows Identification of Electronic
      Transitions of a Molecular Nanoring.
AB  - The role of quantum coherence in photochemical functions of molecular systems
      such as photosynthetic complexes is a broadly debated topic. Coexistence and
      intermixing of electronic and vibrational coherences has been proposed to be
      responsible for the observed long-lived coherences and high energy transfer
      efficiency. However, clear experimental evidence of coherences with different
      origins operating at the same time has been elusive. In this work,
      multidimensional spectra obtained from a six-porphyrin nanoring system are
      analyzed in detail with support from theoretical modeling. We uncover a great
      diversity of separable electronic, vibrational, and mixed coherences and show
      their cooperation in shaping the spectroscopic response. The results permit
      direct assignment of electronic and vibronic states and characterization of the
      excitation dynamics. The clear disentanglement of coherences in molecules with
      extended pi-conjugation opens up new avenues for exploring coherent phenomena and
      understanding their importance for the function of complex systems.

PMID- 28493709
TI  - Rh/DuanPhos-Catalyzed Asymmetric Hydrogenation of beta-Acetylamino Vinylsulfides:
      An Approach to Chiral beta-Acetylamino Sulfides.
AB  - Rh/DuanPhos-catalyzed asymmetric hydrogenation of challenging beta-acetylamino
      vinylsulfides has been developed, affording chiral beta-acetylamino sulfides with
      high yields and excellent ee's (up to 99% ee). This novel methodology provides an
      efficient and concise synthetic route to chiral beta-acetylamino sulfides. The
      potential utility of this protocol in the synthesis of Apremilast has also been
      disclosed.

PMID- 28493711
TI  - Structural Evolution of Sub-10 nm Octahedral Platinum-Nickel Bimetallic
      Nanocrystals.
AB  - Octahedral Pt alloy nanocrystals (NCs) have shown excellent activities as
      electrocatalysts toward oxygen reduction reaction (ORR). As the activity and
      stability of NCs are highly dependent on their structure and the elemental
      distribution, it is of great importance to understand the formation mechanism of
      octahedral NCs and to rationally synthesize shape-controlled alloy catalysts with
      optimized ORR activity and stability. However, the factors controlling the
      structural and compositional evolution during the synthesis have not been well
      understood yet. Here, we systematically investigated the structure and
      composition evolution pathways of Pt-Ni octahedra synthesized with the assistance
      of W(CO)6 and revealed a unique core-shell structure consisting of a Pt core and
      a Pt-Ni alloy shell. Below 140  degrees C, sphere-like pure Pt NCs with the
      diameter of 3-4 nm first nucleated, followed by the isotropic growth of Pt-Ni
      alloy on the seeds at temperatures between 170 and 230  degrees C forming Pt@Pt
      Ni core-shell octahedra with {111} facets. Owing to its unique structure, the
      Pt@Pt-Ni octahedra show an unparalleled stability during potential cycling, that
      is, no activity drop after 10 000 cycles between 0.6 and 1.0 V. This work
      proposes the Pt@Pt-Ni octahedra as a high profile electrocatalyst for ORR and
      reveals the structural and composition evolution pathways of Pt-based bimetallic
      NCs.

PMID- 28493710
TI  - Nuclear Localizing Peptide-Conjugated, Redox-Sensitive Polymersomes for
      Delivering Curcumin and Doxorubicin to Pancreatic Cancer Microtumors.
AB  - Improving the therapeutic index of anticancer agents is an enormous challenge.
      Targeting decreases the side effects of the therapeutic agents by delivering the
      drugs to the intended destination. Nanocarriers containing the nuclear localizing
      peptide sequences (NLS) translocate to the cell nuclei. However, the nuclear
      localization peptides are nonselective and cannot distinguish the malignant cells
      from the healthy counterparts. In this study, we designed a "masked" NLS peptide
      which is activated only in the presence of overexpressed matrix metalloproteinase
      7 (MMP-7) enzyme in the pancreatic cancer microenvironment. This peptide is
      conjugated to the surface of redox responsive polymersomes to deliver doxorubicin
      and curcumin to the pancreatic cancer cell nucleus. We have tested the
      formulation in both two- and three-dimensional cultures of pancreatic cancer and
      normal cells. Our studies revealed that the drug-encapsulated polymeric vesicles
      are significantly more toxic toward the cancer cells (shrinking the spheroids up
      to 49%) compared to the normal cells (shrinking the spheroids up to 24%). This
      study can lead to the development of other organelle targeted drug delivery
      systems for various human malignancies.

PMID- 28493712
TI  - Stimulus-Responsive Degradable Polylactide-Based Block Copolymer Nanoassemblies
      for Controlled/Enhanced Drug Delivery.
AB  - Polylactide (PLA) is biocompatible and FDA-approved for clinical use and thus has
      been a choice of the materials valuable for extensive applications in biomedical
      fields. However, conventionally designed PLA-based amphiphilic block copolymer
      (ABP) nanoassemblies exhibit slow and uncontrolled release of encapsulated drugs
      because of the slow biodegradation of hydrophobic PLA in physiological
      conditions. To improve potentials for clinical use and commercialization of
      conventional PLA-based nanoassemblies, stimulus-responsive degradation (SRD)
      platform has been introduced into the design of PLA-based nanoassemblies for
      enhanced/controlled release of encapsulated drugs. This review summarizes recent
      strategies that allow for the development of PLA-based ABPs and their self
      assembled nanostructures exhibiting SRD-induced enhanced drug release. The review
      focuses on the design, synthesis, and evaluation of the nanoassemblies as
      intracellular drug delivery nanocarriers for cancer therapy. Further, the outlook
      is briefly discussed on the important aspects for the current and future
      development of more effective SRD PLA-based nanoassemblies toward tumor-targeting
      intracellular drug delivery.

PMID- 28493714
TI  - Relativistic Polarizable Embedding.
AB  - Most chemistry, including chemistry where relativistic effects are important,
      occurs in an environment, and in many cases, this environment has a significant
      effect on the chemistry. In nonrelativistic quantum chemistry, a lot of progress
      has been achieved with respect to including environments such as a solvent or
      protein in the calculations, and now is the time to extend the possibilities for
      also doing this in relativistic quantum chemistry. The polarizable embedding (PE)
      model efficiently incorporates electrostatic effects of the environment by
      describing it as a collection of localized electric multipoles and
      polarizabilities obtained through quantum chemical calculations. In this article,
      we present the theory and implementation of four- and exact two-component
      Hamiltonians within a PE framework. We denote the methods the PE-4c-DFT and PE
      X2C-DFT models. The models include a linear response formalism to calculate time
      dependent (TD) properties: PE-TD-4c-DFT and PE-TD-X2C-DFT. With this first
      implementation, we calculate the PE-TD-4c-PBE0 excitation energies of the TcO4-
      and ReO4- ions in an explicit water solvent. This initial investigation focuses
      on the relative size of relativistic and solvent contributions to the excitation
      energies. The solvent effect is divided into an indirect solvent effect due to
      the structural perturbation of the XO4- ion and a direct electrostatic effect.
      The relativistic effects as well as both types of solvent effects are found to
      contribute to a shift in the excitation energies, but they do so to different
      extents depending on the ion and the electronic transition in question.

PMID- 28493715
TI  - Recent Trends in Quantum Chemical Modeling of Enzymatic Reactions.
AB  - The quantum chemical cluster approach is a powerful method for investigating
      enzymatic reactions. Over the past two decades, a large number of highly diverse
      systems have been studied and a great wealth of mechanistic insight has been
      developed using this technique. This Perspective reviews the current status of
      the methodology. The latest technical developments are highlighted, and
      challenges are discussed. Some recent applications are presented to illustrate
      the capabilities and progress of this approach, and likely future directions are
      outlined.

PMID- 28493716
TI  - Bifenthrin Causes Toxicity in Urban Stormwater Wetlands: Field and Laboratory
      Assessment Using Austrochiltonia (Amphipoda).
AB  - Stormwater wetlands are engineered to accumulate sediment and pollutants from
      stormwater and provide environmental value to urban environments. Therefore,
      contaminated sediment risks causing toxicity to aquatic fauna. This research
      identifies contaminants of concern in urban wetland sediments by assessing
      sediment toxicity using the amphipod Austrochiltonia subtenuis. Sediments from 98
      wetlands were analyzed for contaminants, and laboratory bioassays were performed
      with A. subtenuis. Wild Austrochiltonia spp. were also collected from wetlands to
      assess field populations. Random forest modeling was used to identify the most
      important variables predicting survival, growth, and field absence of
      Austrochiltonia spp. Bifenthrin was the most frequently detected pesticide and
      also the most important predictor of Austrochiltonia spp. responses. Copper,
      permethrin, chromium, triclosan, and lead were also important. The median lethal
      effect concentration (LC50) of bifenthrin to laboratory-based A. subtenuis (1.09
      (+/-0.08) MUg/gOC) exposed to wetland sediments was supported by a bifenthrin
      spiked sediment experiment, indicating A. subtenuis is a suitable test species.
      Furthermore, Austrochiltonia spp. were absent from all sites that exceeded the
      calculated bifenthrin LC50, demonstrating the impact of this contaminant on wild
      populations. This research demonstrates the sensitivity of Austrochiltonia spp.
      to urban sediment contamination and identifies bifenthrin as a contaminant of
      concern in urban wetlands.

PMID- 28493713
TI  - Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal
      Growth Factor Dependent Regulation of Renal Drug Transporters.
AB  - The combination of methotrexate with epidermal growth factor receptor (EGFR)
      recombinant antibody, cetuximab, is currently being investigated in treatment of
      head and neck carcinoma. As methotrexate is cleared by renal excretion, we
      studied the effect of cetuximab on renal methotrexate handling. We used human
      conditionally immortalized proximal tubule epithelial cells overexpressing either
      organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and
      OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug
      resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling
      upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based
      pathway analysis were used to predict EGFR-mediated transporter regulation.
      Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol
      bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein
      uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS
      MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial
      transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1
      and BCRP as well as their membrane expressions and transport activities, while
      MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced
      modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological
      inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were
      increased. AKT inhibition reduced all transporters. Exposure to methotrexate for
      24 h led to a decreased viability, an effect that was reversed by cetuximab. In
      conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and
      MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways.
      Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens
      possibilities for further research into nephroprotective comedication therapies.

PMID- 28493717
TI  - [2 + 2]-type Reaction of Metal-Metal sigma-Bond with Fullerene Forming an eta1
      C60 Metal Complex: Mechanistic Details of Formation Reaction and Prediction of a
      New eta1-C60 Metal Complex.
AB  - C60[CpRu(CO)2]2 is only one transition-metal fullerene complex with pure eta1
      coordinated bonds, which was recently synthesized through the reaction between
      dinuclear Ru complex [CpRu(CO)2]2 and C60. Though new properties can be expected
      in the eta1-coordinated metal-fullerene complex, its characteristic features are
      unclear, and the [2 + 2]-type formation reaction is very slow with a very small
      yield. A density functional theory study discloses that the eta1-coordinated bond
      is formed by a large overlap between the Ru dsigma orbital and C psigma one
      involved in the lowest unoccupied molecular orbital (LUMO) (pi*) of C60 unlike
      the well-known eta2-coordinated metal-fullerene complex which has a pi-type
      coordinate bond with metal dpi orbital. The binding energy per one Ru-C bond is
      much smaller than those of eta2-coordinated Pt(PMe3)2(C60) and IrH(CO)(PH3)2(C60)
      because the Ru d orbital exists at low energy. The formation reaction occurs via
      Ru-Ru bond cleavage on the C60 surface followed by a direction change of
      CpRu(CO)2 to afford C60[CpRu(CO)2]2 in a stepwise manner via two asymmetrical
      transition states to avoid a symmetry-forbidden character. The calculated Gibbs
      activation energy (DeltaG degrees ?) is very large and the Gibbs reaction energy
      (DeltaG degrees ) is moderately negative, which are consistent with a very slow
      reaction rate and very small yield. The charge transfer from CpRu(CO)2 to
      fullerene CT(Ru -> C60) is important in the reaction, but it is small due to the
      presence of the Ru d orbital at low energy, which is the reason for the large
      DeltaG degrees ? and moderately negative DeltaG degrees . The use of Li+@C60 is
      theoretically predicted to accelerate the reaction and increase the yield of
      Li+@C60[CpRu(CO)2]2, because the CT(Ru -> C60) is enhanced by the low energy LUMO
      of Li+@C60. It is also predicted that Li+@C60[Re(CO)4(PMe3)]2 is a next promising
      target for the synthesis of the eta1-coordinated metal-fullerene complex, but
      syntheses of C60[Co(CO)4]2, C60[Re(CO)5]2, Li+@C60[Co(CO)4]2, and
      Li+@C60[Re(CO)5]2 are difficult. The use of nonpolar solvent is another important
      factor for the synthesis of the eta1-coordinated metal complex with Li+@C60.

PMID- 28493718
TI  - Tamarixetin 3-O-beta-d-Glucopyranoside from Azadirachta indica Leaves:
      Gastroprotective Role through Inhibition of Matrix Metalloproteinase-9 Activity
      in Mice.
AB  - Neem (Azadirachta indica) is a well-known medicinal and insecticidal plant.
      Although previous studies have reported the antiulcer activity of neem leaf
      extract, the lead compound is still unidentified. The present study reports
      tamarixetin 3-O-beta-d-glucopyranoside (1) from a methanol extract of neem leaves
      and its gastroprotective activity in an animal model. Compound 1 showed
      significant protection against indomethacin-induced gastric ulceration in mice in
      a dose-dependent manner. Moreover, ex vivo and circular dichroism studies
      confirmed that 1 inhibited the enzyme matrix metalloproteinase-9 (MMP-9) activity
      with an IC50 value of ca. 50 MUM. Molecular docking and dynamics showed the
      binding of 1 into the pocket of the active site of MMP-9, forming a coordination
      complex with the catalytic zinc, thus leading to inhibition of MMP-9 activity.

PMID- 28493719
TI  - Theoretical Study on the Open-Shell Singlet Nature and the Second
      Hyperpolarizabilities of Corannulene Derivatives with Two Phenoxyl Radicals.
AB  - Using the spin-unrestricted density functional theory method, we investigate the
      interplay between the diradical character y and second hyperpolarizabilities
      gamma (the third-order nonlinear optical (NLO) properties at the molecular scale)
      of corannulene derivatives with two phenoxyl radicals. This molecule in the
      singlet state exhibits intermediate y and thus displays a significantly larger
      gamma value than the triplet state and the closed-shell bis-phenol analogue. We
      also examine the planar molecules involving a coronene moiety in place of the
      curved corannulene. The intermediate y and large gamma values of the corannulene
      systems are found to originate not from their curved skeleton but from the
      equilibrium between benzenoid/quinoid resonance forms due to delocalization of
      the radical electrons of the terminal phenoxyl rings. The longitudinal gamma
      value of the singlet state is found to be comparable to that of s-indaceno[1,2,3
      cd;5,6,7-c'd']diphenalene, which is known to be one of the organic molecules with
      the largest two-photon absorption cross section in this size of pure
      hydrocarbons. The present system is thus expected to be a promising candidate for
      highly efficient open-shell NLO molecules.

PMID- 28493720
TI  - Tandem Catalysis for CO2 Hydrogenation to C2-C4 Hydrocarbons.
AB  - Conversion of carbon dioxide to C2-C4 hydrocarbons is a major pursuit in clean
      energy research. Despite tremendous efforts, the lack of well-defined catalysts
      in which the spatial arrangement of interfaces is precisely controlled hinders
      the development of more efficient catalysts and in-depth understanding of
      reaction mechanisms. Herein, we utilized the strategy of tandem catalysis to
      develop a well-defined nanostructured catalyst CeO2-Pt@mSiO2-Co for converting
      CO2 to C2-C4 hydrocarbons using two metal-oxide interfaces. C2-C4 hydrocarbons
      are found to be produced with high (60%) selectivity, which is speculated to be
      the result of the two-step tandem process uniquely allowed by this catalyst.
      Namely, the Pt/CeO2 interface converts CO2 and H2 to CO, and on the neighboring
      Co/mSiO2 interface yields C2-C4 hydrocarbons through a subsequent Fischer-Tropsch
      process. In addition, the catalysts show no obvious deactivation over 40 h. The
      successful production of C2-C4 hydrocarbons via a tandem process on a rationally
      designed, structurally well-defined catalyst demonstrates the power of
      sophisticated structure control in designing nanostructured catalysts for
      multiple-step chemical conversions.

PMID- 28493721
TI  - Effects of Hydrotropic Salt on the Nanoscopic Dynamics of DTAB Micelles.
AB  - Effects of a hydrotropic salt, sodium salicylate (NaSal), on the dynamic behavior
      of cationic dodecyltrimethylammonium bromide (DTAB) micelles as studied using
      dynamic light scattering (DLS) and quasielastic neutron scattering (QENS)
      techniques are reported here. DLS study showed that the addition of NaSal leads
      to a decrease in the apparent diffusion coefficient of the whole micelle
      indicating micellar growth. QENS data analysis suggested that observed dynamics
      involves two distinct motions, lateral motion of the surfactant over the curved
      micellar surface and localized segmental motion of the surfactant. It is found
      that the addition of NaSal slows down the lateral motion of DTAB while the
      localized segmental motion of the DTAB chain is not affected much. An atomistic
      molecular dynamics (MD) simulation was performed to gain further insight into the
      underlying phenomena. MD simulation results are found to be consistent with the
      experimental observations. MD simulation revealed that location of the salicylate
      ions on the micellar surface and their strong electrostatic association with
      their oppositely charged surfactant headgroup are the major factors in slowing
      down the lateral motion of the DTAB molecule. In the present work, a quantitative
      description of the effects of NaSal on the nanoscopic dynamics of DTAB micelles
      and its correlation with the microstructure of the micelle is provided.

PMID- 28493722
TI  - Synthesis of 4-Halo-3(2H)-furanones Using Intramolecular Cyclization of Sulfonium
      Salts.
AB  - A simple and efficient synthesis of 4-halo-3(2H)-furanones by halogenative
      intramolecular cyclization of sulfonium salts is described, which can expedite
      the production of a variety of 4-bromo- or 4-iodo-3(2H)-furanones, useful
      synthetic building blocks, in good to high yield under mild conditions.

PMID- 28493723
TI  - Influence of Conventional Surfactants on the Self-Assembly of a Bola Type
      Amphiphilic Peptide.
AB  - Structural and morphological regulation is a distinctly important topic in
      peptide self-assembly, and is also regarded as the fundamental point in peptide
      based biomaterials development. In this paper, we showed that adding anionic
      surfactant SDS to a bola amphiphilic peptide KI4K could result in the
      reconstruction of beta-sheet secondary structure besides the changes in self
      assembly morphologies from nanotubes to helical ribbons, nanofibers, or straight
      nanotapes according to the negatively stained transmission electron microscopy,
      atomic force microscopy, circular dichroism spectroscopy, and Fourier transform
      infrared spectroscopy results. The inducing effect of SDS was observed at both
      above and below its CMC but with different transformation rates. Through
      comparison to other surfactants, including CTAB, C12EO4, and AOT, we proposed
      that the transitions of KI4K self-assemblies induced by anionic surfactants could
      be mainly attributed to the effect of hydrophobic interaction and electrostatic
      attraction between surfactants and peptide molecules. Rheological property
      measurement and dye adsorption experiments were also carried out to evaluate the
      properties of hydrogels formed by the peptide/surfactant hybrids. The samples
      formed self-supporting hydrogels at proper SDS or AOT concentrations, and the
      charges of hydrogel could be regulated by peptide to surfactant ratio.

PMID- 28493724
TI  - Tuning the Viscoelasticity of Peptide Vesicles by Adjusting Hydrophobic Helical
      Blocks Comprising Amphiphilic Polypeptides.
AB  - Amphiphilic block polypeptides of poly(sarcosine)-b-(l-Val-Aib)6 and
      poly(sarcosine)-b-(l-Leu-Aib)6 and their stereoisomers were self-assembled in
      water. Three kinds of binary systems of poly(sarcosine)-b-(l-Leu-Aib)6 with
      poly(sarcosine)-b-poly(d-Leu-Aib)6, poly(sarcosine)-b-poly(l-Val-Aib)6, or
      poly(sarcosine)-b-(d-Val-Aib)6 generated vesicles of ca. 200 nm diameter. The
      viscoelasticity of the vesicle membranes was evaluated by the nanoindentation
      method using AFM in water. The elasticity of the poly(sarcosine)-b-(l-Leu
      Aib)6/poly(sarcosine)-b-poly(d-Leu-Aib)6 vesicle was 11-fold higher than that of
      the egg yolk liposome but decreased in combinations of the Leu- and Val-based
      amphiphilic polypeptides. The membrane elasticity is found to be adjustable by a
      suitable combination of helical blocks in terms of stereocomplex formation and
      the interdigitation of side chains among helices in the molecular assemblies.

PMID- 28493725
TI  - Questionnaire and behavioral task measures of impulsivity are differentially
      associated with body mass index: A comprehensive meta-analysis.
AB  - Although impulsivity has been implicated in the development and maintenance of
      obesity, evidence linking impulsivity to obesity has been mixed. These mixed
      findings may be related to differences in the type of impulsivity measures used
      and the varied domains of impulsivity assessed by each measure. The present meta
      analysis aimed to examine the impact of measurement selection on the relationship
      between impulsivity and body mass index (BMI). A total of 142 articles met
      inclusion criteria and were comprised of 315,818 participants. Effect sizes
      consisted of Fisher's z-transformed correlation coefficients, which were weighted
      by the inverse variance to establish the grand mean estimate of the relationship
      between impulsivity and BMI. Overall weighted mean effect sizes also were
      computed for each type and domain of impulsivity measure. Moderator analyses were
      conducted using a mixed-effects approach to determine if the relationship between
      impulsivity and BMI varied between the types of impulsivity measures used. On
      average, participants were 32.25 (SD = 12.41) years of age, with a BMI of 26.63
      (SD = 5.73) kg/m2. The overall relationship between impulsivity and BMI was small
      but significant (r = .07). Behavioral task measures of impulsivity produced
      significantly larger effect sizes (r = .10) than did questionnaire measures of
      impulsivity (r = .05). Domains of impulsivity that assessed disinhibited
      behaviors (r = .10), attentional deficits (r = .11), impulsive decision-making (r
      = .10), and cognitive inflexibility (r = .17) produced significant effect sizes.
      These meta-analytic findings demonstrate that impulsivity is positively
      associated with BMI and further document that this association varies by the type
      of impulsivity measure used and the domain of impulsivity assessed. (PsycINFO
      Database Record

PMID- 28493726
TI  - Anticipatory coarticulation and the minimal planning unit of speech.
AB  - One of the most persistent arguments against the segment as the minimal planning
      unit is that the seemingly ubiquitous, thus, presumed obligatory, nature of
      anticipatory coarticulation (AC) effects favors the syllable or a larger unit. By
      contrast, we present the results of 3 experiments showing that AC is not
      ubiquitous, but graded and variable based on (a) phonological availability and
      (b) the specific criterion to initiate articulation adopted by a speaker. We
      further argue that phonological encoding is parallel. These results point to (a)
      the segment, and not the syllable, as the minimal planning unit and (b) a
      flexible planning scope. Implications with respect to the current formulation of
      AC regarding phonological availability and the minimal unit of speech
      articulation are discussed. (PsycINFO Database Record

PMID- 28493727
TI  - Military sexual trauma is associated with eating disorders, while combat exposure
      is not.
AB  - OBJECTIVE: There are strong associations among trauma and eating disorders.
      However, while trauma and eating disorders are more common among veterans than
      other populations, there is little information on how military-specific stressors
      affect eating disorder risk. This study's objective was to determine whether
      military sexual trauma and combat exposure were independent predictors of eating
      disorders among women veterans, a high-risk group. METHOD: Participants were
      women age 18-70, using VA medical center services, without psychotic disorders or
      suicidal ideation (N = 407). We estimated a cross-sectional logistic regression
      model to predict eating disorders (anorexia, bulimia, binge eating disorder) as a
      function of military sexual trauma and combat exposure, adjusting for demographic
      variables. RESULTS: Sixty-six percent of participants reported military sexual
      trauma, 32% reported combat exposure, and 15% met eating disorder criteria. Mean
      age was 49 years (SD = 13); 40% were veterans of color. Women reporting military
      sexual trauma had twice the odds of an eating disorder compared to women who did
      not (odds ratio [OR]: 2.03; 95% CI [1.03-3.98]). Combat exposure was not
      associated with eating disorders. Asian race (OR: 3.36; 95% CI [1.26-8.97]) and
      age (OR: 1.03; 95% CI [1.01-1.06]) were associated with eating disorders.
      CONCLUSIONS: The high rates of military sexual trauma and eating disorders
      highlight a need for continued work. Results suggest that it may be useful to
      focus on women reporting military sexual trauma when implementing eating disorder
      screening and treatment programs. Given associations among trauma, eating
      disorders, obesity, and mortality, such efforts could greatly improve veteran
      health. (PsycINFO Database Record

PMID- 28493728
TI  - Internal and community recourses' contribution to level of posttraumatic symptoms
      The case of tourists after the earthquake in Nepal, 2015.
AB  - OBJECTIVE: The current study focused on tourists who were caught in the middle of
      Nepal's, 2015 earthquake, and survived. We examined the contribution of internal
      (coping flexibility and emotional regulation) and community resources (sense of
      belonging to the community) to tourist's level of post traumatic stress disorder
      symptoms. METHOD: A cross-sectional sample survey was conducted to collect data
      from 145 tourists between 2 week to 3 months after the earthquake. RESULTS: The
      findings indicated first, that longer time which had elapsed since the earthquake
      was correlated with lower level of posttraumatic symptoms. In addition, higher
      versatility and cognitive reappraisal were associated with fewer symptoms of
      posttrauma, whereas higher expressive suppression was associated with a higher
      level of symptoms. Finally, the more the tourists believed they would get help
      from other Israelis, the lower was their level of posttraumatic symptoms.
      CONCLUSIONS: Tourists in a disaster area can be aided to develop a variety of
      emotional, cognitive, and behavioral strategies that will assist them in coping
      with the trauma. Furthermore, gathering tourists from the same country to conduct
      interventions on the community level can be helpful. (PsycINFO Database Record

PMID- 28493730
TI  - Behavioral health services in urban American Indian health organizations: A
      descriptive portrait.
AB  - The federal Indian Health Service (IHS) is the primary funding source for health
      services designated for American Indians (AIs; Gone & Trimble, 2012). Urban
      Indian health organizations (UIHOs), funded in part by IHS, are typically the
      only sites in large metropolitan settings offering treatments tailored to AI
      health needs. This is a first look at how mental health treatment is structured
      at UIHOs. UIHO staff at 17 of 34 UIHOs responded to our request to participate
      (50%), 14 employed behavioral health program directors who could complete the
      survey on behalf of their programs, and 11 of these submitted complete data
      regarding their current treatment practices and personal attitudes toward
      empirically supported treatments. Reported treatment profiles differed less than
      expected from available data on national outpatient clinics from the National
      Mental Health Services Survey (Substance Abuse and Mental Health Services
      Administration [SAMHSA], 2014), and program director attitudes toward empirically
      supported treatments were similar to national norms reported by Aarons et al.
      (2010). One way in which treatment differed was in the reported use of
      traditional AI healing services. All program directors indicated that traditional
      AI healing services were available within their behavioral health programs in
      some form. These findings seem promising for the development of new empirically
      supported treatments for AI clients, but also raise concerns, given what is known
      about AI treatment preferences and mental health disparities. For example,
      traditional healing services are often considered "alternative medicine," outside
      the purview of evidence-based practice as typically construed by mental health
      services researchers. This potential conflict is a subject for future research.
      (PsycINFO Database Record

PMID- 28493729
TI  - The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial
      psychometric evaluation in military veterans.
AB  - The Clinician-Administered PTSD Scale (CAPS) is an extensively validated and
      widely used structured diagnostic interview for posttraumatic stress disorder
      (PTSD). The CAPS was recently revised to correspond with PTSD criteria in the
      fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      5; American Psychiatric Association, 2013). This article describes the
      development of the CAPS for DSM-5 (CAPS-5) and presents the results of an initial
      psychometric evaluation of CAPS-5 scores in 2 samples of military veterans (Ns =
      165 and 207). CAPS-5 diagnosis demonstrated strong interrater reliability (k =
      .78 to 1.00, depending on the scoring rule) and test-retest reliability (k =
      .83), as well as strong correspondence with a diagnosis based on the CAPS for DSM
      IV (CAPS-IV; k = .84 when optimally calibrated). CAPS-5 total severity score
      demonstrated high internal consistency (alpha = .88) and interrater reliability
      (ICC = .91) and good test-retest reliability (ICC = .78). It also demonstrated
      good convergent validity with total severity score on the CAPS-IV (r = .83) and
      PTSD Checklist for DSM-5 (r = .66) and good discriminant validity with measures
      of anxiety, depression, somatization, functional impairment, psychopathy, and
      alcohol abuse (rs = .02 to .54). Overall, these results indicate that the CAPS-5
      is a psychometrically sound measure of DSM-5 PTSD diagnosis and symptom severity.
      Importantly, the CAPS-5 strongly corresponds with the CAPS-IV, which suggests
      that backward compatibility with the CAPS-IV was maintained and that the CAPS-5
      provides continuity in evidence-based assessment of PTSD in the transition from
      DSM-IV to DSM-5 criteria. (PsycINFO Database Record

PMID- 28493731
TI  - Pilot data of a brief veteran peer intervention and its relationship to mental
      health treatment engagement.
AB  - Underutilization of mental health care is a significant problem among veterans.
      Offering peer support may improve mental health care engagement. This
      observational pilot study was conducted using an institutional review board
      approved data repository to preliminarily evaluate the association and potential
      impact of a clinic-based veteran peer outreach strategy on treatment engagement
      and dropout. Veteran peer outreach coordinators (VPOCs) provided systematic
      contact (a) within 1 week after clinical evaluation and (b) 1 month after the
      patient's first treatment session to patients entering treatment at a specialty
      mental health clinic that provides military-informed mental health care to post
      9/11 veterans and service members. Individuals were 102 consecutive Operation
      Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veteran psychotherapy
      referrals seen at an outpatient clinic. At 6 months, participants who received
      both contacts from VPOC had more psychotherapy sessions (M = 10.85, SD = 8.25)
      compared with those who had received no contact (M = 5.47, SD = 6.41) from VPOCs,
      t = 2.56, p < .05. The dropout rate was also significantly lower for those who
      received both peer outreach contacts (17.39%) compared with those who received
      only 1 VPOC contact (51.11%) or no VPOC contact (43.75%), chi2 = 7.27, p < .05.
      Veteran peer outreach may be associated with better engagement in mental health
      treatment and lower dropout. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 28493732
TI  - Psychological flexibility mitigates effects of PTSD symptoms and negative urgency
      on aggressive behavior in trauma-exposed veterans.
AB  - Recent literature suggests that posttraumatic stress disorder (PTSD) symptoms can
      interact with personality factors to predict externalizing behaviors. Engagement
      in externalizing behaviors such as substance abuse and aggressive behavior may,
      in turn, increase risk for further trauma exposure and a more chronic course of
      PTSD. In order to better understand how to intervene on this cycle, the current
      study aimed to identify factors that could explain risk for externalizing
      behaviors among trauma-exposed veterans. Moreover, we aimed to identify whether
      psychological flexibility, a skill drawn from acceptance and commitment therapy
      (ACT), may mitigate risk for engagement in externalizing behavior. Results
      indicated that PTSD symptoms indirectly predicted externalizing behavior via
      negative urgency, or the propensity to act rashly in the context of distress.
      Moreover, psychological flexibility moderated this relationship such that
      negative urgency was less strongly associated with aggressive behavior at high
      levels of psychological flexibility. These results highlight moments of intense
      distress as important targets for therapeutic intervention, and psychological
      flexibility as a potentially important therapeutic skill for reducing
      externalizing behavior among trauma-exposed individuals. (PsycINFO Database
      Record

PMID- 28493733
TI  - Dimensional conceptualizations of impulsivity.
AB  - Impulsivity is a transdiagnostic dimension of crucial importance to understanding
      psychopathology, as it is highly relevant to a wide array of maladaptive life
      outcomes including substance use, criminality, and other risky behaviors. There
      exist a variety of operationalizations of impulsivity across the literature
      distinct nomological networks. In fact, research suggests that "impulsivity" is a
      multifaceted construct comprised of at least 4 distinct traits that have unique
      pathways to maladaptive behaviors. Those traits are positive and negative
      urgency, sensation seeking, premeditation, and perseverance. Thus, it is crucial
      that any diagnostic system, or model of maladaptive traits, capture the nuances
      among these impulsigenic traits. The present study investigated the
      conceptualization of impulsigenic traits within the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013).
      Alternative personality disorder model and an alternative trait model to
      determine how well they captured these variants. This study obtained
      questionnaire ratings and behavioral task data from 450 community-dwelling adults
      oversampled for a history of involvement in the legal and/or mental health
      systems. The results showed that although the DSM-5 trait model captures well a
      broad conceptualization of impulsivity, some lower-order facets lack specificity.
      (PsycINFO Database Record

PMID- 28493734
TI  - Pubertal timing, racial identity, neighborhood, and school context among Black
      adolescent females.
AB  - OBJECTIVES: This study bridges the empirical research on pubertal timing effects,
      racial identity, and school and neighborhood context to understand the pubertal
      development and depression link among Black adolescent females. We examined
      whether racial identity content dimensions moderated the relation between
      pubertal timing and depressive symptoms among Black adolescent females and the
      moderating capacity of school and neighborhood racial composition. METHOD: We
      administered measures of pubertal development, racial identity, and depressive
      symptoms to a sample of 217 Black adolescent females, aged 14 to 18. We assessed
      racial centrality, private regard, and public regard and used archival data to
      obtain the racial composition of participants' neighborhoods and schools.
      RESULTS: The results indicated that high racial centrality levels were linked to
      depressive symptoms for adolescent girls with late pubertal timing relative to
      their early counterparts, which was stronger for girls attending not majority
      Black schools. The results also indicated that low public regard levels were
      linked to depressive symptoms among adolescent girls with early pubertal timing
      relative to their late counterparts, which was stronger for girls attending not
      majority Black schools. CONCLUSIONS: The current study provides evidence that
      racial identity and school racial context moderate the effects of pubertal timing
      differentially for early and late maturing Black girls. The results support the
      notion that the psychological effects of pubertal timing on internalizing
      symptoms are context dependent. (PsycINFO Database Record

PMID- 28493735
TI  - Greater than the sum of its parts: Development of a measure of collectivism among
      Asians.
AB  - OBJECTIVES: Collectivism can contextualize subjective cultural experiences, yet
      operationalization and measurement approaches for understanding this construct
      among Asians and Asian Americans have been discrepant. Inconsistency has resulted
      from diverse levels of analyses, unidimensional versus multidimensional
      approaches to organizing related subconstructs, and different degrees of cultural
      specificity of existing instruments. The Brief Collectivism Questionnaire (BCQ)
      was developed to address these limitations in assessing general collectivism in
      Asian cultures, while capturing its diverse attitudinal and behavioral
      manifestations, using a bifactor framework. METHOD: Data were collected from 2
      samples of Asian American and Asian international students (N1 = 267: Mage =
      20.4, 48.7% women; N2 = 375: Mage = 19.0, 55.6% women). The structure underlying
      collectivism was examined in exploratory (Study 1) and confirmatory (Study 2)
      factor analyses. Correlational and hierarchical multiple regression analyses
      tested the BCQ's validity, particularly the extent to which broadband
      collectivism and content-specific subdomains overlapped with existing measures of
      the construct (Study 3). RESULTS: A bifactor structure with 1 general factor of
      collectivism and 3 specific factors (Prosocial Motivations, Maintaining Harmony,
      and Concern for Face) demonstrated the best fit for the data and supported the
      conceptual framework. The BCQ showed adequate internal consistency reliability,
      convergent and discriminant validity, and concurrent and incremental validity
      predicting depression and openness toward treatment seeking. CONCLUSIONS: The BCQ
      appears to be a multidimensional, psychometrically sound measure that assesses
      broadband and narrowband contents of collectivism among Asians. The bifactor
      structure integrates diverse conceptualizations of individual-level collectivism,
      and clarifies how this construct is related to adjustment outcomes. (PsycINFO
      Database Record

PMID- 28493736
TI  - Promoting mental health recovery and improving clinical assessment using video
      technology.
AB  - TOPIC: Although individuals with medical problems (e.g., diabetes, hypertension)
      can monitor their symptoms using objective measures (e.g., blood glucose, blood
      pressure), objective measures are not typically used by individuals with
      psychotic disorders to monitor symptoms of mental illness. PURPOSE: To examine
      the benefits and limitations of the use of video self-observation for treatment
      of individuals with psychotic disorders. SOURCES USED: The authors reviewed
      studies examining video self-observation among individuals with severe mental
      illnesses. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Individuals with psychotic
      disorders who viewed videos of themselves while symptomatic reported some benefit
      to this approach, with 1 study showing sustained improvement in understanding of
      mental illness. Still, some individuals reported negative feelings about the
      process, and also attributed symptoms to stress or drug abuse rather than their
      psychotic disorder. The authors found no studies examining the potential for
      video self-observation as a strategy to improve clinical decision-making in the
      context of mental health care. Implications of this approach for mental health
      recovery and clinical practice are discussed. (PsycINFO Database Record

PMID- 28493737
TI  - Autonomy support for conflictual and stigmatized identities: Effects on ownership
      and psychological health.
AB  - Important others' perceptions influence self-perceptions. This presents a
      challenge for the critical developmental task of integrating all aspects of
      identity, as identities that are devalued or stigmatized by society are harder to
      own than valued ones. Across 3 studies, we tested the idea that conflictual or
      stigmatized identities are harder to own, or integrate into the self, than are
      nonconflictual ones, and we examine how receiving autonomy support for an
      identity-support for authentic identity exploration and expression-can facilitate
      ownership of that identity. Cross-sectional (n = 543), experience-sampling (n =
      66), and experimental methods (n = 209) tested the dynamics of autonomy
      supportive others on identity ownership. Data from these studies converge to show
      that conflictual identities are indeed harder to own than nonconflictual ones,
      but that autonomy support predicts greater ownership and psychological health,
      especially for conflictual identities. In the final study, we replicate these
      dynamics in 3 identities stigmatized by society: sexual minority, ethnic
      minority, and gender minority identities. Findings reveal the importance of
      integrating all aspects of identity-particularly those that are conflictual or
      stigmatized-into one's self-concept. We consider implications for counseling and
      clinical practice, as well as broadly for the psychological health of stigmatized
      individuals. (PsycINFO Database Record

PMID- 28493738
TI  - Helping others increases meaningful work: Evidence from three experiments.
AB  - The aim of the current research was to examine whether manipulating task
      significance increased the meaningfulness of work among students (Study 1), an
      online sample of working adults (Study 2), and public university employees (Study
      3). In Study 1, students completed a typing task for the benefit of themselves, a
      charity, or someone they knew would directly benefit from their work. People who
      worked to benefit someone else, rather than themselves, reported greater task
      meaningfulness. In Study 2, a representative, online sample of employees
      reflected on a time when they worked to benefit themselves or someone else at
      work. Results revealed that people who reflected on working to benefit someone
      else, rather than themselves, reported greater work meaningfulness. In Study 3,
      public university employees participated in a community intervention by working
      as they normally would, finding new ways to help people each day, or finding
      several new ways to help others on a single day. People who helped others many
      times in a single day experienced greater gains in work meaningfulness over time.
      Across 3 experimental studies, we found that people who perceived their work as
      helping others experienced more meaningfulness in their work. This highlights the
      potential mechanisms practitioners, employers, and other parties can use to
      increase the meaningfulness of work, which has implications for workers' well
      being and productivity. (PsycINFO Database Record

PMID- 28493739
TI  - Sample size determination for examining interaction effects in factorial designs
      under variance heterogeneity.
AB  - Moderation analysis is a vital aspect of research in education, management,
      psychology, and related disciplines. Although several methodological artifacts
      have been identified and examined, heterogeneity of variance remains one of the
      unique and problematic factors known as detrimental to statistical power in the
      detection of moderating effects. To alleviate the difficulty in assessing
      moderation because of low statistical power, this article describes feasible
      solutions to sample size calculations for tests of hypothesized interactions
      between categorical variables under variance heterogeneity. Detailed numerical
      illustrations and simulation studies are presented to demonstrate the feature and
      usefulness of the suggested technique for 2- and 3-way factorial designs.
      Moreover, SAS and R programs are provided to facilitate the implementation of the
      proposed sample size procedure. (PsycINFO Database Record

PMID- 28493740
TI  - Independent learning of spatial and nonspatial sequences.
AB  - A small number of studies have examined whether learning the structures of two
      uncorrelated sequences can proceed independently of one another. Limitations in
      those studies have left their results open to alternative explanations. The
      present study addressed the limitations. The visuospatial serial reaction time
      task, initially introduced by Mayr (1996), was used to examine whether learning
      the structure of a sequence of visuospatial target locations (spatial sequence)
      and learning the structure of a sequence of target identities and responses
      (nonspatial sequence) can proceed independently of one another. Employing a dual
      sequence/single-sequence paradigm, learning a nonspatial sequence did not affect
      learning a spatial sequence. This suggests that spatial sequence learning and
      nonspatial sequence learning can proceed independently of one another. (PsycINFO
      Database Record

PMID- 28493741
TI  - How actions taken (or not) under alcohol influence inhibitory control and
      perceived impairment.
AB  - Consumption of alcohol can lead to the impairment of the ability to suppress
      inappropriate responses. However, alcohol-induced disinhibition does not occur in
      all contexts in the real world. Therefore, the purpose of this study was to
      examine if actions taken (or not) under alcohol will impact observed inhibitory
      control and how behavioral control requirements under alcohol alter perceived
      levels of impairment. Participants (n = 40) of equal sex who were social drinkers
      participated in a 3 session laboratory study that involved the administration of
      placebo, 0.45g/kg, and 0.65g/kg doses of alcohol. Participants were randomly
      assigned to a modified cued go/no-go reaction time (RT) task that included more
      go trials (activational condition) or more no-go trials (inhibitory condition).
      On all sessions after dose administration, participants completed their assigned
      cued go/no-go computer task and gave subjective ratings of impairment. The
      results indicated that participants in the activational condition under all doses
      of alcohol, but particularly the highest dose of alcohol, displayed poorer
      behavioral control (i.e., greater inhibitory failures) but self-reported lower
      perceived impairment, when compared to participants in the inhibitory condition.
      Therefore, this study provides laboratory evidence that alcohol consumption in an
      active setting will lead to greater disinhibition and reduced perceptions of
      impairment of behavior. The findings highlight the importance of the drinking
      setting when examining the acute effects of alcohol and suggest potential avenues
      for harm reduction for individuals who have difficulty controlling their alcohol
      intake. (PsycINFO Database Record

PMID- 28493742
TI  - Effects of alcohol, initial gambling outcomes, impulsivity, and gambling
      cognitions on gambling behavior using a video poker task.
AB  - Drinking and gambling frequently co-occur, and concurrent gambling and drinking
      may lead to greater negative consequences than either behavior alone. Building on
      prior research on the effects of alcohol, initial gambling outcomes, impulsivity,
      and gambling cognitions on gambling behaviors using a chance-based (nonstrategic)
      slot-machine task, the current study explored the impact of these factors on a
      skill-based (strategic) video poker task. We anticipated larger average bets and
      greater gambling persistence under alcohol relative to placebo, and expected
      alcohol effects to be moderated by initial gambling outcomes, impulsivity, and
      gambling cognitions. Participants (N = 162; 25.9% female) were randomly assigned
      to alcohol (target BrAC = .08g%) or placebo and were given $10 to wager on a
      simulated video poker task, which was programmed to produce 1 of 3 initial
      outcomes (win, breakeven, or lose) before beginning a progressive loss schedule.
      Despite evidence for validity of the video poker task and alcohol administration
      paradigm, primary hypotheses were not supported. Individuals who received alcohol
      placed smaller wagers than participants in the placebo condition, though this
      effect was not statistically significant, and the direction of effects was
      reversed in at-risk gamblers (n = 41). These findings contradict prior research
      and suggest that alcohol effects on gambling behavior may differ by gambling type
      (nonstrategic vs. strategic games). Interventions that suggest alcohol is
      universally disinhibiting may be at odds with young adults' lived experience and
      thus be less effective than those that recognize the greater complexity of
      alcohol effects. (PsycINFO Database Record

PMID- 28493743
TI  - Stimulus selectivity of drug purchase tasks: A preliminary study evaluating
      alcohol and cigarette demand.
AB  - The use of drug purchase tasks to measure drug demand in human behavioral
      pharmacology and addiction research has proliferated in recent years. Few studies
      have systematically evaluated the stimulus selectivity of drug purchase tasks to
      demonstrate that demand metrics are specific to valuation of or demand for the
      commodity under study. Stimulus selectivity is broadly defined for this purpose
      as a condition under which a specific stimulus input or target (e.g., alcohol,
      cigarettes) is the primary determinant of behavior (e.g., demand). The overall
      goal of the present study was to evaluate the stimulus selectivity of drug
      purchase tasks. Participants were sampled from the Amazon.com's crowdsourcing
      platform Mechanical Turk. Participants completed either alcohol and soda purchase
      tasks (Experiment 1; N = 139) or cigarette and chocolate purchase tasks
      (Experiment 2; N = 46), and demand metrics were compared to self-reported use
      behaviors. Demand metrics for alcohol and soda were closely associated with
      commodity-similar (e.g., alcohol demand and weekly alcohol use) but not commodity
      different (e.g., alcohol demand and weekly soda use) variables. A similar pattern
      was observed for cigarette and chocolate demand, but selectivity was not as
      consistent as for alcohol and soda. Collectively, we observed robust selectivity
      for alcohol and soda purchase tasks and modest selectivity for cigarette and
      chocolate purchase tasks. These preliminary outcomes suggest that demand metrics
      adequately reflect the specific commodity under study and support the continued
      use of purchase tasks in substance use research. (PsycINFO Database Record

PMID- 28493745
TI  - "Treating adult survivors of childhood emotional abuse and neglect: A new
      framework": Correction to Grossman et al. (2017).
AB  - Reports an error in "Treating adult survivors of childhood emotional abuse and
      neglect: A new framework" by Frances K. Grossman, Joseph Spinazzola, Marla Zucker
      and Elizabeth Hopper (American Journal of Orthopsychiatry, 2017, Vol 87[1], 86
      93). In the article, in the second sentence of the third paragraph of the "The
      Empirical Base for CBP" section, "construction of a life narrative" should have
      read "construction of a trauma narrative." The full corrected sentence follows:
      "Therefore, the trauma treatment component traditionally focused upon
      construction of a trauma narrative must be expanded to address the effects of
      trauma on our clients' entire life narratives, including their development of a
      sense of self and social identity." (The following abstract of the original
      article appeared in record 2017-01147-002.) This article provides the outline of
      a new framework for treating adult survivors of childhood emotional abuse and
      neglect. Component-based psychotherapy (CBP) is an evidence-informed model that
      bridges, synthesizes, and expands upon several existing schools, or theories, of
      treatment for adult survivors of traumatic stress. These include approaches to
      therapy that stem from more classic traditions in psychology, such as
      psychoanalysis, to more modern approaches including those informed by feminist
      thought. Moreover, CBP places particular emphasis on integration of key concepts
      from evidence-based treatment models developed in the past few decades predicated
      upon thinking and research on the effects of traumatic stress and processes of
      recovery for survivors. (PsycINFO Database Record

PMID- 28493746
TI  - Sexual objectification: The common thread connecting myriad forms of sexual
      violence against women.
AB  - In this article, the authors focus on the linkages between objectification and
      current societal manifestations of sexual violence toward women to make the case
      that everyday instances of objectification can provide the foundation for more
      extreme forms of violence. First, they formally introduce the notion of
      objectification and explain its origins and its consequences in those who
      perpetrate and those who experience it. Next, they use objectification as a lens
      through which to consider several related, but distinct, societal problems,
      including: sexual assault of college women, harassment of women in work settings,
      and sex trafficking of women in the United States and around the world. Finally,
      they offer potential solutions, which, if implemented at individual,
      organizational, and societal levels, could reduce violence against women in its
      many forms. (PsycINFO Database Record

PMID- 28493744
TI  - Does menthol cigarette use moderate the effect of nicotine metabolism on short
      term smoking cessation?
AB  - The nicotine metabolite ratio (NMR) has been shown to predict response to the
      transdermal nicotine patch, such that faster nicotine metabolism is associated
      with a lower abstinence rate. Menthol cigarette use, versus nonmenthol cigarette
      use, slows nicotine metabolism and therefore may attenuate the effect of NMR on
      smoking abstinence. In this study, we evaluated whether cigarette type (menthol
      vs. nonmenthol) modified the association between NMR and short-term abstinence.
      This was a secondary analysis examining treatment in the first 8 weeks of 21
      mg/day nicotine patch therapy in a completed clinical trial (n = 474). Menthol
      cigarette use was based on self-report. NMR was defined dichotomously (0 = fast,
      1 = slow) to distinguish between fast (>=0.47) versus slow NMR. Using logistic
      regression analysis, we tested whether cigarette type moderated the association
      between NMR and bioverified 7-day point prevalence abstinence at Week 8.
      Covariates include nicotine dependence, age, race, and gender. Three hundred two
      participants reported smoking menthol cigarettes, of which 234 (77%) were
      classified as slow NMR. Among the 172 nonmenthol smokers, 136 were classified as
      slow NMR (79%). Contrary to our expectations, the NMR *Cigarette Type interaction
      effect on abstinence was not significant (odds ratio [OR] = 0.91, p = .86).
      Excluding the interaction variable, fast NMR was associated with decreased
      likelihood of abstinence (OR = 0.55, p = .03), but menthol cigarette use was not
      (OR = 1.15, p = .56). Further exploration of risk factors among menthol cigarette
      smokers, especially among racially diverse and light smokers, could clarify the
      association between menthol cigarette use and poorer smoking outcomes. (PsycINFO
      Database Record

PMID- 28493747
TI  - Leader social accounts of subordinates' unethical behavior: Examining observer
      reactions to leader social accounts with moral disengagement language.
AB  - When providing social accounts (Sitkin & Bies, 1993) for the unethical conduct of
      subordinates, leaders may use language consistent with cognitive strategies
      described by Bandura (1991, 1999) in his work on moral disengagement. That is,
      leader's social accounts may reframe or reconstrue subordinates' unethical
      conduct such that it appears less reprehensible. We predict observers will
      respond negatively to leaders when they use moral disengagement language within
      social accounts and, specifically, observers will ostracize these leaders. In
      addition, we predict that observer moral disengagement propensity moderates this
      effect, such that the relationship between leaders' use of moral disengagement
      language within a social account and ostracism is stronger when observer moral
      disengagement propensity is lower versus higher. Finally, we predict that the
      reason why observers ostracize the leader is because observers perceive the
      leader's social account with moral disengagement language as unethical. Thus,
      perceived leader social account ethicality is predicted to mediate the
      interaction effect of leader's use of moral disengagement language within social
      accounts and observer moral disengagement propensity on ostracism. Results from
      an experiment and field study support our predictions. Implications for theory
      and practice are discussed. (PsycINFO Database Record

PMID- 28493748
TI  - The face of fear and anger: Facial width-to-height ratio biases recognition of
      angry and fearful expressions.
AB  - The ability to rapidly and accurately decode facial expressions is adaptive for
      human sociality. Although judgments of emotion are primarily determined by
      musculature, static face structure can also impact emotion judgments. The current
      work investigates how facial width-to-height ratio (fWHR), a stable feature of
      all faces, influences perceivers' judgments of expressive displays of anger and
      fear (Studies 1a, 1b, & 2), and anger and happiness (Study 3). Across 4 studies,
      we provide evidence consistent with the hypothesis that perceivers more readily
      see anger on faces with high fWHR compared with those with low fWHR, which
      instead facilitates the recognition of fear and happiness. This bias emerges when
      participants are led to believe that targets displaying otherwise neutral faces
      are attempting to mask an emotion (Studies 1a & 1b), and is evident when faces
      display an emotion (Studies 2 & 3). Together, these studies suggest that target
      facial width-to-height ratio biases ascriptions of emotion with consequences for
      emotion recognition speed and accuracy. (PsycINFO Database Record

PMID- 28493749
TI  - Maternal emotion dysregulation and the functional organization of preschoolers'
      emotional expressions and regulatory behaviors.
AB  - Although psychopathology in mothers is known to be a significant risk factor for
      child outcomes, less is known about how emotion dysregulation, a transdiagnostic
      feature that cuts across many diagnoses, shapes emotion-related parenting
      practices and the development of emotion regulation in offspring. Building upon
      previous research that examined the functional relations between emotions and
      regulatory actions in children, we sought to examine the association of maternal
      emotion dysregulation and emotion socialization with these functional links in an
      at-risk community sample of mother-preschooler (children ages 36-60 months) dyads
      that oversampled for mothers with elevated symptoms of borderline personality
      disorder (n = 68). We found that maternal emotion dysregulation was associated
      with children displaying more sadness and engaging in less problem solving during
      the Locked Box Task, which is designed to elicit anger. Maternal emotion
      dysregulation was also associated with children being more distracted and talking
      less in the context of sadness. Maternal nonsupportive emotion socialization
      responses were associated with children engaging in more defiant behaviors
      throughout the task and using less problem solving in the context of happiness,
      whereas maternal supportive emotion socialization responses were associated with
      more play throughout the task and less talking in the context of sadness, above
      and beyond the effect of maternal emotion dysregulation. These findings indicate
      that maternal emotion dysregulation and nonsupportive emotion socialization
      practices are both meaningfully associated with the development of aberrant
      patterns of emotional and behavioral responding during the preschool years.
      (PsycINFO Database Record

PMID- 28493750
TI  - The ideal road not taken: The self-discrepancies involved in people's most
      enduring regrets.
AB  - Research on the structural features of people's most enduring regrets has focused
      on whether they result from having acted or having failed to act. Here we focus
      on a different structural feature, their connection to a person's self-concept.
      In 6 studies, we predict and find that people's most enduring regrets stem more
      often from discrepancies between their actual and ideal selves than their actual
      and ought selves. We also provide evidence that this asymmetry is at least partly
      due to differences in how people cope with regret. People are quicker to take
      steps to cope with failures to live up to their duties and responsibilities
      (ought-related regrets) than their failures to live up to their goals and
      aspirations (ideal-related regrets). As a consequence, ideal-related regrets are
      more likely to remain unresolved, leaving people more likely to regret not being
      all they could have been more than all they should have been. (PsycINFO Database
      Record

PMID- 28493751
TI  - Identity change among smokers and ex-smokers: Findings from the ITC Netherlands
      Survey.
AB  - Successful smoking cessation appears to be facilitated by identity change, that
      is, when quitting or nonsmoking becomes part of smokers' and ex-smokers' self
      concepts. The current longitudinal study is the first to examine how identity
      changes over time among smokers and ex-smokers and whether this can be predicted
      by socioeconomic status (SES) and psychosocial factors (i.e., attitude, perceived
      health damage, social norms, stigma, acceptance, self-evaluative emotions, health
      worries, expected social support). We examined identification with smoking (i.e.,
      smoker self-identity) and quitting (i.e., quitter self-identity) among a large
      sample of smokers (n = 742) and ex-smokers (n = 201) in a cohort study with
      yearly measurements between 2009 and 2014. Latent growth curve modeling was used
      as an advanced statistical technique. As hypothesized, smokers perceived
      themselves more as smokers and less as quitters than do ex-smokers, and
      identification with smoking increased over time among smokers and decreased among
      ex-smokers. Furthermore, psychosocial factors predicted baseline identity and
      identity development. Socioeconomic status (SES) was particularly important.
      Specifically, lower SES smokers and lower SES ex-smokers identified more strongly
      with smoking, and smoker and quitter identities were more resistant to change
      among lower SES groups. Moreover, stronger proquitting social norms were
      associated with increasing quitter identities over time among smokers and ex
      smokers and with decreasing smoker identities among ex-smokers. Predictors of
      identity differed between smokers and ex-smokers. Results suggest that SES and
      proquitting social norms should be taken into account when developing ways to
      facilitate identity change and, thereby, successful smoking cessation. (PsycINFO
      Database Record

PMID- 28493752
TI  - Problem gambling symptomatology and alcohol misuse among adolescents: A parallel
      process latent growth curve model.
AB  - The objective of the current study was to examine the possible temporal
      associations between alcohol misuse and problem gambling symptomatology from
      adolescence through to young adulthood. Parallel-process latent growth curve
      modeling was used to examine the trajectories of alcohol misuse and symptoms of
      problem gambling over time. Data were from a sample of adolescents recruited for
      the Leisure, Lifestyle, and Lifecycle Project in Alberta, Canada (n = 436), which
      included 4 assessments over 5 years. There was an average decline in problem
      gambling symptoms followed by an accelerating upward trend as the sample reached
      the legal age to gamble. There was significant variation in the rate of change in
      problem gambling symptoms over time; not all respondents followed the same
      trajectory. There was an average increase in alcohol misuse over time, with
      significant variability in baseline levels of use and the rate of change over
      time. The unconditional parallel process model indicated that higher baseline
      levels of alcohol misuse were associated with higher baseline levels of problem
      gambling symptoms. In addition, higher baseline levels of alcohol misuse were
      associated with steeper declines in problem gambling symptoms over time. However,
      these between-process correlations did not retain significance when covariates
      were added to the model, indicating that one behavior was not a risk factor for
      the other. The lack of mutual influence in the problem gambling symptomatology
      and alcohol misuse processes suggest that there are common risk factors
      underlying these two behaviors, supporting the notion of a syndrome model of
      addiction. (PsycINFO Database Record

PMID- 28493753
TI  - Visual attention to alcohol cues and responsible drinking statements within
      alcohol advertisements and public health campaigns: Relationships with drinking
      intentions and alcohol consumption in the laboratory.
AB  - Both alcohol advertising and public health campaigns increase alcohol consumption
      in the short term, and this may be attributable to attentional capture by alcohol
      related cues in both types of media. The present studies investigated the
      association between (a) visual attention to alcohol cues and responsible drinking
      statements in alcohol advertising and public health campaigns, and (b) next-week
      drinking intentions (Study 1) and drinking behavior in the lab (Study 2). In
      Study 1, 90 male participants viewed 1 of 3 TV alcohol adverts (conventional
      advert; advert that emphasized responsible drinking; or public health campaign;
      between-subjects manipulation) while their visual attention to alcohol cues and
      responsible drinking statements was recorded, before reporting their drinking
      intentions. Study 2 used a within-subjects design in which 62 participants (27%
      male) viewed alcohol and soda advertisements while their attention to
      alcohol/soda cues and responsible drinking statements was recorded, before
      completing a bogus taste test with different alcoholic and nonalcoholic drinks.
      In both studies, alcohol cues attracted more attention than responsible drinking
      statements, except when viewing a public health TV campaign. Attention to
      responsible drinking statements was not associated with intentions to drink
      alcohol over the next week (Study 1) or alcohol consumption in the lab (Study 2).
      However, attention to alcohol portrayal cues within alcohol advertisements was
      associated with ad lib alcohol consumption in Study 2, although attention to
      other types of alcohol cues (brand logos, glassware, and packaging) was not
      associated. Future studies should investigate how responsible drinking statements
      might be improved to attract more attention. (PsycINFO Database Record

PMID- 28493754
TI  - Discrepancy in caregiving expectations predicts problematic alcohol use among
      caregivers of trauma injury patients six months after ICU admission.
AB  - This prospective study examined the influence of caregiving variables on the
      development of problematic alcohol use among family members of patients admitted
      to an urban Level I trauma center. Data were collected from 124 caregivers 48 hrs
      after initial hospitalization of their family member. The final sample included
      81 participants (24.6% male; Mage = 47.8) who completed their follow-up
      assessment at 6 months. Hierarchical linear and logistic regression analyses
      assessed increases in consumption and odds of a positive screen for problematic
      alcohol use in association with caregiver burden, actual time spent in the
      caregiving role, and caregiving differential (i.e., anticipated time spent
      caregiving at baseline in relation to actual time caregiving at 6 months). At 6
      months, 24.7% of caregivers screened positive for problematic alcohol use.
      Results uniquely highlighted caregiving differential as a significant predictor
      of both increases in general alcohol consumption (DeltaR2 = .06, p < .01) and
      odds of screening positive for problematic alcohol use at 6 months (Odds Ratio =
      1.05, 95% CI [1.02-1.09]). More specifically, our adjusted model found that
      providing 10% more time caregiving, relative to expectations at baseline, was
      associated with an increase in the probability of problematic alcohol use by 22%
      (95% CI: 8-37%) at 6 months. These results suggest that a discrepancy in
      expectations regarding anticipated time caregiving and actual time caregiving,
      rather than solely the amount of caregiving or perceived caregiver burden, may be
      an important predictor of caregiver alcohol use 6 months after a family member's
      ICU hospitalization. (PsycINFO Database Record

PMID- 28493755
TI  - Affect contagion between mothers and infants: Examining valence and touch.
AB  - Mothers and their babies represent one of the closest dyadic units and thus
      provide a powerful paradigm to examine how affective states are shared, and
      result in, synchronized physiologic responses between two people. We recruited
      mothers and their 12- to 14-month-old infants (Ndyads = 98) to complete a lab
      study in which mothers were initially separated from their infants and assigned
      to either a low-arousal positive/relaxation condition, intended to elicit
      parasympathetic nervous system (PNS) reactivity, or a high-arousal
      negative/stress task, intended to elicit sympathetic nervous system (SNS)
      reactivity. Upon reunion, infants were placed either on their mothers' laps
      (touch condition) or in a high chair next to the mother (no-touch condition). We
      then examined if the babies SNS and/or PNS responses changed from their baseline
      levels and how the dyads' physiological responses-both PNS and SNS responses
      synchronized over time as a function of mothers' affect manipulation and touch
      condition. Three noteworthy findings were observed. First, infants of mothers
      assigned to the relaxation task showed greater PNS increases and PNS covariation.
      Second, infants of mothers assigned to the stress task showed stronger SNS
      covariation with their mothers over time. Finally, infants who sat on their
      mothers' laps (i.e., touch condition) showed stronger SNS covariation than those
      in the no-touch condition. Taken together, these results suggest that mothers'
      affective states-low-arousal positive states as well as high-arousal negative
      states-can be "caught" by their infants, and that touch can play a critical role
      in stress contagion. (PsycINFO Database Record

PMID- 28493756
TI  - Functional consequences of compositional spatial representations elicited during
      conceptual control of visual spatial attention.
AB  - Reference frames are ubiquitous in spatial cognition, and they have been
      especially important in the visual attention literature. Researchers typically
      invoke these constructs to explain how the same physical location can be defined
      in different ways depending on changes in the reference point. However, when
      researchers invoke reference frames for this purpose, they also tend to invoke a
      construct-the Cartesian coordinate system-that has a specific compositional
      structure. This conclusion may not be warranted though because reference frames
      can be used to define a location without being compositional in nature. The
      present study used an attention cuing paradigm to examine the potential
      consequences of encoding spatial locations within compositional (coordinate)
      spatial representations. Experiment 1 used 75% valid, compositional cues that
      conveyed separate information about the likely direction and distance of the
      target. The main results were consistent with the notion that a Cartesian
      coordinate reference system was used to interpret these cues which in turn
      elicited a compositional gradient that reflected the combined activation arising
      from the separate spatial dimensions. Experiment 2 ruled out an alternative
      account and Experiment's 3 and 4 examined the dynamic nature of these gradients
      over time. These findings were interpreted within a theory of conceptual control
      that distinguished between conceptual and perceptual representations of space.
      Conceptual representations are compositional and can be used to guide attention
      from one object to another. But conceptual representations depend on
      noncompositional, perceptual representations to bind the activations arising from
      their separate spatial dimensions, much like nonspatial feature dimensions do.
      (PsycINFO Database Record

PMID- 28493757
TI  - Argumentation and the diffusion of counter-intuitive beliefs.
AB  - Research in cultural evolution has focused on the spread of intuitive or
      minimally counterintuitive beliefs. However, some very counterintuitive beliefs
      can also spread successfully, at least in some communities-scientific theories
      being the most prominent example. We suggest that argumentation could be an
      important factor in the spread of some very counterintuitive beliefs. A first
      experiment demonstrates that argumentation enables the spread of the
      counterintuitive answer to a reasoning problem in large discussion groups,
      whereas this spread is limited or absent when participants can show their answers
      to each other but cannot discuss. A series of experiments using the technique of
      repeated transmission show that, in the case of the counterintuitive belief
      studied: (a) arguments can help spread this belief without loss; (b) conformist
      bias does not help spread this belief; and (c) authority or prestige bias play a
      minimal role in helping spread this belief. Thus, argumentation seems to be
      necessary and sufficient for the spread of some counterintuitive beliefs.
      (PsycINFO Database Record

PMID- 28493758
TI  - Lying because we care: Compassion increases prosocial lying.
AB  - Prosocial lies, or lies intended to benefit others, are ubiquitous behaviors that
      have important social and economic consequences. Though emotions play a central
      role in many forms of prosocial behavior, no work has investigated how emotions
      influence behavior when one has the opportunity to tell a prosocial lie-a
      situation that presents a conflict between two prosocial ethics: lying to prevent
      harm to another, and honesty, which might also provide benefits to the target of
      the lie. Here, we examine whether the emotion of compassion influences prosocial
      lying, and find that compassion causally increases and positively predicts
      prosocial lying. In Studies 1 and 2, participants evaluated a poorly written
      essay and provided feedback to the essay writer. Experimentally induced
      compassion felt toward the essay writer (Study 1) and individual differences in
      trait compassion (Study 2) were positively associated with inflated feedback to
      the essay writer. In both of these studies, the relationship between compassion
      and prosocial lying was partially mediated by an enhanced importance placed on
      preventing emotional harm. In Study 3, we found moderation such that
      experimentally induced compassion increased lies that resulted in financial gains
      for a charity, but not lies that produced financial gains for the self. This
      research illuminates the emotional underpinnings of the common yet morally
      complex behavior of prosocial lying, and builds on work highlighting the
      potentially harmful effects of compassion-an emotion typically seen as socially
      beneficial. (PsycINFO Database Record

PMID- 28493759
TI  - "Characterizing autism-relevant social behavior in poodles (Canis familiaris) via
      owner report": Correction to Zamzow et al. (2017).
AB  - Reports an error in "Characterizing Autism-Relevant Social Behavior in Poodles
      via Owner Report" by Rachel M. Zamzow, Lisa Lit, Shelley Hamilton and David Q.
      Beversdorf (Journal of Comparative Psychology, Advanced Online Publication, Mar
      13, 2017, np). In the article, the scientific name for the species was missing in
      the title. All versions of this article have been corrected. (The following
      abstract of the original article appeared in record 2017-11247-001.) Autism
      spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by
      deficits in social communication and the presence of restricted, repetitive
      behaviors. It can be difficult to model the complex behavioral features of this
      disorder with rodent models, which have limited similarity to human behaviors.
      The domestic dog may be a promising model of complex human behavior, including
      core features of ASD. The present study examines ASD-relevant social behavior in
      Miniature and Standard Poodles using an owner-report questionnaire with questions
      adapted from the Autism Diagnostic Observation Schedule (Lord, Rutter, DiLavore,
      & Risi, 2000). A previous study identified 3 behavioral constructs examined by
      this questionnaire: initiation of reciprocal social behaviors, response to social
      interaction, and communication. In the present study, confirmatory and
      experimental factor analyses used to assess how collected data fit with the
      previous model revealed moderate model fit and a similar factorial structure.
      Between-breed comparisons across these factors and at the individual question
      level revealed differences between Miniature and Standard Poodles in showing
      behaviors. Cluster analyses used to group dogs within each breed according to
      social behavior identified smaller subgroups of dogs with less social behavior
      across all 3 factors compared with the average within each breed. Within- and
      between-breed differences in social behavior warrant investigation of genetic
      variation underlying this complex trait as it relates to ASD-relevant behavior.
      (PsycINFO Database Record

PMID- 28493760
TI  - Exploration of the ASCO and ESMO Value Frameworks for Antineoplastic Drugs.
AB  - PURPOSE: In 2015, both ASCO and the European Society for Medical Oncology (ESMO)
      proposed frameworks to quantify the benefit of antineoplastic drugs in the face
      of rising costs. We applied these frameworks to drugs approved by the US Food and
      Drug Administration over the past 12 years and examined relationships between
      costs and benefits. METHODS: We searched FDA.gov for drugs that received initial
      approval for solid tumors from 2004 to 2015 and calculated the ASCO Net Health
      Benefit version 2016 (NHB16) and 2015 (NHB15) and the ESMO Magnitude of Clinical
      Benefit Scale scores for each drug. We calculated descriptive statistics and
      explored correlations and associations among benefit scores, cost, and
      independent variables. RESULTS: We identified 55 drug approvals supported by
      phase II (18.2%) and III (81.8%) trials, with primary outcomes of overall
      survival (36.4%), progression-free survival (43.6%), or response rate (20.0%). No
      significant association was found between NHB16 and year of approval ( P = .81),
      organ system ( P = .20), or trial comparator arm ( P = .17), but trials with
      progression-free survival outcomes were associated with higher scores ( P =
      .007). Both NHB15 and Magnitude of Clinical Benefit Scale scores were
      approximately normally distributed, but only a moderate correlation existed
      between them ( r = 0.40, P = .006). No correlation between benefit score and cost
      (NHB16, r = 0.19; ESMO, r = -0.07) was found. Before 2010, two (15.3%) of 13
      approved drugs exceeded $500/NHB point * month compared with 10 (25.0%) of 40
      drugs subsequently approved. CONCLUSION: Our analysis of the ASCO and ESMO value
      frameworks illuminates the heterogeneous benefit of new medications and
      highlights challenges in constructing a unified concept of drug value. Drug
      benefit does not correlate with cost, and the number of high cost/benefit
      outliers has increased.

PMID- 28493761
TI  - Pursuing Interventions for an Incurable Cancer: Adding to Hope or Delusion?

PMID- 28493762
TI  - Why Burnout Is So Hard to Fix.

PMID- 28493763
TI  - Fluorescent PCR detection of mecA in drug resistant MRSA: a methodological study.

PMID- 28493764
TI  - Nursing: it's just what we do.

PMID- 28493765
TI  - Long-term urethral catheterisation: guidelines for community nurses.
AB  - An estimated 3% of people living in the community and 12% of those living in
      residential care use long-term urethral catheterisation for the management of
      urine drainage. This article provides an overview of safe practice for
      catheterisation in the community setting, highlighting the need for competent and
      safe patient assessments. It also aims to provide a rationale for product
      choices.

PMID- 28493766
TI  - UK Chief Nursing Officers: shaping the future of the profession.
AB  - In celebration of International Nurses Day, Jane Cummings, Charlotte McArdle,
      Fiona McQueen and Jean White, Chief Nursing Officers (CNOs) for England, Northern
      Ireland, Scotland and Wales.

PMID- 28493767
TI  - Nursing a critically ill tetanus patient in an intensive care unit in Zambia.
AB  - The global incidence of tetanus has been gradually reducing. Improvements in
      vaccination and health education programmes and the World Health Organization
      campaign to eradicate maternal and neonatal tetanus have all resulted in fewer
      presentations globally. Unfortunately, tetanus mortality remains a significant
      problem for many developing countries, owing to inadequate vaccination programmes
      or to conflict or humanitarian disasters during which vaccination programmes are
      stopped or there is sporadic cover. This case study explores the care of a
      tetanus patient in an intensive care unit in Zambia, a lower-middle-income
      country in sub-Saharan Africa.

PMID- 28493769
TI  - We have made history, but what about our future?

PMID- 28493768
TI  - Protecting whistleblowers against discrimination in the NHS.
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
      new Department of Health proposals to prohibit discrimination against former
      whistleblowers when they apply for another job in the NHS.

PMID- 28493770
TI  - Lower urinary tract infections in women.
AB  - In her lifetime, a woman is highly likely to develop at least one lower urinary
      tract infection. Early detection and treatment are key. Being aware of
      predisposing factors for infection and understanding appropriate diagnosis and
      treatment regimens will help nurses in both primary and acute care manage these
      patients correctly. This will not only benefit patients but will also help
      prevent incorrect antimicrobial management and avoid unplanned admissions. This
      aim of this article is to provide nurses with the information they need to best
      advise both colleagues and patients on how to manage lower urinary tract
      infections in women.

PMID- 28493771
TI  - Introducing a device to assist in the application of anti-embolism stockings.
AB  - Using a device to help with the application and removal of anti-embolism
      stockings, often called thromboembolic deterrent stockings (TEDS), can
      potentially facilitate greater adherence to the use of stockings, and potentially
      reduce the risk of deep-vein thrombosis (DVT). This article describes a quality
      improvement project which used the Plan, Do, Study, Act (PDSA) cycle to
      facilitate the introduction of a device to aid in the application of
      thromboembolic deterrent stockings in an orthopaedic ward. The project findings
      showed that Neo-slip(r), a product designed to facilitate the use of compression
      stockings, can be effectively introduced into an orthopaedic ward, with positive
      feedback from both staff and patients.

PMID- 28493772
TI  - Strength through adversity: developing resilience though international working.

PMID- 28493773
TI  - How amendments to the Mental Health Act 1983 will change police powers.
AB  - Richard Griffith, Senior Lecturer in Health Law at Swansea University, considers
      the impact on nursing practice of amendments to police powers under the Mental
      Health Act 1983 introduced by the Policing and Crime Act 2017.

PMID- 28493774
TI  - Urinary catheter-related visits to the emergency department and implications for
      community services.
AB  - : Thousands of patients live with urinary catheters and the potential
      complications deriving from long-term use. Disjointed community services may
      result in patients attending the emergency department (ED) to manage catheter
      complications. AIM: to conduct a service review of catheterised patients
      attending the ED of a large London hospital; to describe incidence, reasons for
      attendance and cost to inform future planning for out-of-hospital care. METHOD: a
      catheter collaborative, consisting of multidisciplinary health professionals and
      patients, formulated survey questions. Patients were identified from the
      electronic patient record by searching for the code 'urological complaint'. One
      month of clinical records were retrospectively reviewed and analysed using
      descriptive statistics. RESULTS: 287 patients attended the department with
      urological complaints: 41 (14%) had urinary catheter problems, of these 24 (59%)
      patients were discharged and 17 (41%) were admitted for further treatment. Stays
      in ED varied from 1 hour 13 minutes to 17 hours (mean = 4.8 hours). A total of 9
      patients (38%) were sent home during antisocial hours (9 pm to 7 am), 4 patients
      were discharged between midnight and 2 am. Patients admitted had mean stays of
      4.11 days. Most admissions were short term for intravenous (IV) treatments; 3
      patients were hospitalised for 20 days. A total of 14 patients (34%) were
      diagnosed with catheter-related infections: 11 (79%) had bladder infections and 3
      (21%) had septicaemia. All 14 patients (100%) had urine-culture-confirmed
      infections, mainly from coliform, proteus and pseudomonas species. A total of 20
      patients (49%) received antibiotic treatment. The majority of patients received
      an initial IV dose followed, where required, by oral treatment on discharge.
      CONCLUSIONS: many catheterised patients had complex needs with high rates of
      urinary infections and admissions for urosepsis. High attendance related less to
      old age but more to complexity of history, such as neurological conditions and
      disability. Only a proportion of these patients could be safely treated by
      district nurse teams. A significant proportion would require more responsive
      community services with several spells of short-term input (e.g. daily or more
      than once-daily visits) and access to diagnostics, microbiology, pharmaceutical
      input and IV treatments.

PMID- 28493776
TI  - Nurses: A Voice to Lead.
AB  - The International Council of Nurses celebrates nurses' contributions to the
      Sustainable Development Goals.

PMID- 28493775
TI  - The key to personalised medicine.
AB  - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, has been
      brushing up on her understanding of genomics, and the opportunities it presents
      to the NHS.

PMID- 28493777
TI  - Let's face the future together.

PMID- 28493778
TI  - Urinary continence care for older people in the acute setting.

PMID- 28493779
TI  - Understanding the global causes and costs of patient harm.
AB  - John Tingle, Reader in Health Law at Nottingham Trent University, discusses the
      Organisation for Economic Co-operation and Development's report on the economics
      of patient safety.

PMID- 28493780
TI  - Nursing students' experiences of mentorship in their final placement.
AB  - AIM: The aim of this study was to explore final-year students' experiences of the
      mentorship role in their final placement and, in particular, to establish their
      expectations of the mentorship role, as well as their support and supervision
      needs. METHOD: Seven final-placement students were recruited from one Scottish
      university, using purposive sampling. Heideggerian phenomenology was chosen as
      the underpinning philosophical approach because of its emphasis on the 'lived
      experience'. Data were generated using unstructured interviews and analysed using
      a modified version of Colaizzi's procedural steps. RESULTS: Five themes emerged
      from the data: 'being more independent', 'support', 'belongingness', 'feedback'
      and 'anticipatory anxiety'. DISCUSSION: Participants who had a positive
      experience of mentorship were exposed to a 'good' learning environment. As a
      result, they felt supported, received adequate opportunities to practise
      management skills, had a sense of 'belonging' within the nursing team and had
      regular feedback. Those who had a negative experience complained of not getting
      the opportunity to develop essential management skills and being dismissed for
      trying to be proactive. In addition, feedback was reported to be lacking. This
      experience resulted in reduced confidence levels, which left them feeling
      unprepared for the transition to registered nurse. CONCLUSION: The clinical
      learning environment itself and support from the mentor are key factors that
      influence student preparation for registration. Without this level of support,
      students may be left feeling unprepared to deal with the transition.

PMID- 28493781
TI  - Juggling two roles: flexibility is the key.

PMID- 28493782
TI  - Is CPR always appropriate? A personal perspective from working in East Africa.

PMID- 28493783
TI  - Your nursing degree: an international ticket to see the world.

PMID- 28493784
TI  - Religion, spirituality and belief: is this the business of nurses?
AB  - Janet Scammell, Associate Professor (Nursing), Bournemouth University, considers
      whether nurses receive sufficient education on religion and spirituality in pre
      registration education.

PMID- 28493785
TI  - Working in partnership: Somaliland.

PMID- 28493786
TI  - Mitigating perceptual error with 'look, listen, feel'.
AB  - Duncan Hamilton, Second Year Student, Adult Nursing, University of Surrey, shares
      how he came to reconsider the arguments for a hands-on approach to taking a
      pulse.

PMID- 28493787
TI  - Impact of Therapy on Recovery during Rehabilitation in Patients with Traumatic
      Spinal Cord Injury.
AB  - Evidence-based planning of rehabilitation interventions is important to improving
      cost efficiency while maintaining patient and system outcomes. This article aims
      to explore the relationship between rehabilitation therapy, functional outcome,
      bed utilization, and care costs after traumatic spinal cord injury (tSCI). A
      retrospective review of 262 persons with tSCI admitted to an inpatient
      rehabilitation facility from 2005-2012 was conducted. Treatment variables and
      outcome measures included rehabilitation length of stay (LOS), days to
      rehabilitation (onset), hours and intensity of therapy, and Functional
      Independence Measure (FIM). Polynomial regression models and generalized additive
      models were applied to explore the relationship between therapy hours and motor
      FIM change. Simulation modeling was used to assess the impact of hypothetically
      increasing therapy intensity. Patients were grouped by injury as: C1-4 American
      Spinal Injury Association (ASIA) Impairment Scale (AIS) A,B,C; C5-8 AIS A,B,C; T1
      S5 AIS A,B,C; and AIS D. The sample was 85% male, mean age 45.9, median LOS 102
      days, and mean therapy intensity 5.7 h/week. Motor FIM change was positively
      associated with total hours of therapy (beta = 0.40, p < 0.0001) up to a certain
      time point, adjusted for age, gender, injury, complications, and rehabilitation
      onset. Hypothetically increasing therapy intensity by 50% and 100% resulted in
      average motor FIM efficiency gain ranging between 0.04-0.07 and 0.1-0.17,
      respectively, across injury groups. The hypothetical changes resulted in
      reductions in the average LOS and bed utilization rate, translating to cost
      savings of $20,000 and $50,000 (2011 CAD) for the +50% and +100% scenarios,
      respectively. The results highlight the importance of monitoring functional
      change throughout rehabilitation after tSCI and the need for customized
      therapeutic strategies.

PMID- 28493788
TI  - Development of In Vitro Embryo Production System Using Collagen Matrix Gel
      Attached with Vascular Endothelial Growth Factor Derived from Interleukin-1 Beta
      Treated Porcine Endometrial Tissue.
AB  - The aim of this study was to establish an embryo culture system using collagen
      gel attached with vascular endothelial growth factor (VEGF) derived from
      interleukin-1 beta (IL-1beta)-treated endometrial tissues from pigs. Endometria
      were separated from the porcine uterus at the follicular phase of the estrous
      cycle and were cultured with IL-1beta. The collagen gels coincubated with IL
      1beta-treated endometria (C, without endometrial tissue; CE, with endometrial
      tissue; and CEI, IL-1beta-treated endometrial tissue) were used for embryo
      culture. We found that, compared with the comparable figures in the control
      group, prostaglandin synthase-2 (PTGS-2) mRNA was increased in IL-1beta-treated
      endometrial tissue (p < 0.05). The VEGF protein was not observed in collagen gel
      coincubated without endometrial tissue (C); however, it was detected in collagen
      gels coincubated with endometrial tissue (CE and CEI). The embryo cleavage rates
      and blastocyst formation did not differ among the treatment groups. The
      proportion of blastocysts did not differ among the groups. However, the number of
      blastocyst cells was significantly (p < 0.05) higher in the CEI group than in the
      other groups. These results clarify the effects of the intrauterine environment
      on preimplantation embryos and may be useful in research on the effects of
      extracellular matrix- and cytokine-treated endometrial tissue on embryo
      development.

PMID- 28493789
TI  - Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of
      Fibrosis at Baseline and 15-Month Follow-up.
AB  - Purpose To evaluate associations between pulmonary function and both quantitative
      analysis and visual assessment of thin-section computed tomography (CT) images at
      baseline and at 15-month follow-up in subjects with idiopathic pulmonary fibrosis
      (IPF). Materials and Methods This retrospective analysis of preexisting
      anonymized data, collected prospectively between 2007 and 2013 in a HIPAA
      compliant study, was exempt from additional institutional review board approval.
      The extent of lung fibrosis at baseline inspiratory chest CT in 280 subjects
      enrolled in the IPF Network was evaluated. Visual analysis was performed by using
      a semiquantitative scoring system. Computer-based quantitative analysis included
      CT histogram-based measurements and a data-driven textural analysis (DTA). Follow
      up CT images in 72 of these subjects were also analyzed. Univariate comparisons
      were performed by using Spearman rank correlation. Multivariate and longitudinal
      analyses were performed by using a linear mixed model approach, in which models
      were compared by using asymptotic chi2 tests. Results At baseline, all CT-derived
      measures showed moderate significant correlation (P < .001) with pulmonary
      function. At follow-up CT, changes in DTA scores showed significant correlation
      with changes in both forced vital capacity percentage predicted (rho = -0.41, P <
      .001) and diffusing capacity for carbon monoxide percentage predicted (rho = 
      0.40, P < .001). Asymptotic chi2 tests showed that inclusion of DTA score
      significantly improved fit of both baseline and longitudinal linear mixed models
      in the prediction of pulmonary function (P < .001 for both). Conclusion When
      compared with semiquantitative visual assessment and CT histogram-based
      measurements, DTA score provides additional information that can be used to
      predict diminished function. Automatic quantification of lung fibrosis at CT
      yields an index of severity that correlates with visual assessment and functional
      change in subjects with IPF. (c) RSNA, 2017.

PMID- 28493790
TI  - Endometrial Carcinoma: MR Imaging-based Texture Model for Preoperative Risk
      Stratification-A Preliminary Analysis.
AB  - Purpose To evaluate the associations among mathematical modeling with the use of
      magnetic resonance (MR) imaging-based texture features and deep myometrial
      invasion (DMI), lymphovascular space invasion (LVSI), and histologic high-grade
      endometrial carcinoma. Materials and Methods Institutional review board approval
      was obtained for this retrospective study. This study included 137 women with
      endometrial carcinomas measuring greater than 1 cm in maximal diameter who
      underwent 1.5-T MR imaging before hysterectomy between January 2011 and December
      2015. Texture analysis was performed with commercial research software with
      manual delineation of a region of interest around the tumor on MR images (T2
      weighted, diffusion-weighted, and dynamic contrast material-enhanced images and
      apparent diffusion coefficient maps). Areas under the receiver operating
      characteristic curve and diagnostic performance of random forest models
      determined by using a subset of the most relevant texture features were estimated
      and compared with those of independent and blinded visual assessments by three
      subspecialty radiologists. Results A total of 180 texture features were extracted
      and ultimately limited to 11 features for DMI, 12 for LVSI, and 16 for high-grade
      tumor for random forest modeling. With random forest models, areas under the
      receiver operating characteristic curve, sensitivity, specificity, accuracy,
      positive predictive value, and negative predictive value were estimated at 0.84,
      79.3%, 82.3%, 81.0%, 76.7%, and 84.4% for DMI; 0.80, 80.9%, 72.5%, 76.6%, 74.3%,
      and 79.4% for LVSI; and 0.83, 81.0%, 76.8%, 78.1%, 60.7%, and 90.1% for high
      grade tumor, respectively. Sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of visual assessment for DMI were
      84.5%, 82.3%, 83.2%, 77.7%, and 87.8% (reader 3). Conclusion The mathematical
      models that incorporated MR imaging-based texture features were associated with
      the presence of DMI, LVSI, and high-grade tumor and achieved equivalent accuracy
      to that of subspecialty radiologists for assessment of DMI in endometrial cancers
      larger than 1 cm. However, these preliminary results must be interpreted with
      caution until they are validated with an independent data set, because the small
      sample size relative to the number of features extracted may have resulted in
      overfitting of the models. (c) RSNA, 2017 Online supplemental material is
      available for this article.

PMID- 28493792
TI  - Transthoracic Echocardiography: Pitfalls and Limitations as Delineated at Cardiac
      CT and MR Imaging-Erratum.

PMID- 28493791
TI  - Recurrent Shoulder Instability in a Young, Active, Military Population and Its
      Professional Implications.
AB  - BACKGROUND: Shoulder instability is a topic of significant interest within the
      sports medicine literature, particularly regarding recurrence rates and the ideal
      treatment indications and techniques. Little has been published specifically
      addressing the occupational implications of symptomatic recurrent shoulder
      instability. HYPOTHESIS: Previous arthroscopic repair will continue to be a
      significant predisposing factor for recurrent instability in a young, active
      population, and that recurrent instability may have a negative effect on college
      graduation and postgraduate occupational selection. STUDY DESIGN: Case series.
      LEVEL OF EVIDENCE: Level 4. METHODS: We conducted a retrospective review of
      approved medical waivers for surgical treatment of anterior shoulder dislocation
      or instability prior to matriculation at the US Military Academy or the US Naval
      Academy for the graduating classes of 2010 to 2013. Statistical analysis was
      performed to determine the incidence and risk factors for recurrence and to
      determine the impact on graduation rate and occupation selection. RESULTS: Fifty
      nine patients were evaluated; 34% developed recurrent anterior instability.
      Patients with previous arthroscopic repair had a significantly higher incidence
      of recurrence (38%, P = 0.044). Recurrent shoulder instability did not
      significantly affect graduation rates or self-selected occupation ( P >= 0.05).
      CONCLUSION: There is a significant rate of recurrent shoulder instability after
      primary surgical repair, particularly among young, active individuals. In
      addition, arthroscopic repair resulted in a significantly higher recurrence rate
      compared with open repair in our population. Surgical repair for shoulder
      instability should not necessarily preclude young individuals from pursuing (or
      being considered for) occupations that may place them at greater risk of
      recurrence. CLINICAL RELEVANCE: The risk of recurrent instability is greater than
      the rate typically described, which may suggest that some subpopulations are at
      greater risk than others. A unique data point regarding instability is the effect
      on occupation selection.

PMID- 28493794
TI  - The Thymus: A Comprehensive Review-Erratum.

PMID- 28493795
TI  - Diagnosis and Management of Complications from Percutaneous Biliary Tract
      Interventions-Erratum.

PMID- 28493796
TI  - Traumatic Rib Injury: Patterns, Imaging Pitfalls, Complications, and Treatment
      Erratum.

PMID- 28493797
TI  - Invited Commentary on "Radiologic-Pathologic Correlation of Primary and Secondary
      Cardiomyopathies".

PMID- 28493798
TI  - Nontraumatic Lesions of the Scalp: Practical Approach to Imaging Diagnosis:
      Neurologic/Head and Neck Imaging.

PMID- 28493800
TI  - IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms.
AB  - Thymic epithelial neoplasms are rare malignancies that arise from the thymus and
      include thymoma, thymic carcinoma, and thymic neuroendocrine tumors. At least 15
      different stage classifications have been proposed for thymic epithelial
      neoplasms and used to varying degrees in clinical practice, many of which have
      been constructed from small groups of patients. Traditionally, the Masaoka and
      Masaoka-Koga staging systems have been the schemes most commonly employed, and
      the latter has been recommended for use by the International Thymic Malignancy
      Interest Group (ITMIG). An official, consistent stage classification system has
      recently been recognized by the American Joint Committee on Cancer (AJCC) and the
      Union for International Cancer Control (UICC), which are responsible for defining
      stage classifications for neoplasms. To establish this stage classification
      system, the International Association for the Study of Lung Cancer (IASLC) and
      ITMIG amassed a large retrospective database and evaluated this group of cases to
      develop proposals for the eighth edition of the stage classification manuals. For
      this endeavor, IASLC provided funding and statistical analysis and ITMIG provided
      the involvement of the clinicians and researchers actively participating in the
      study of thymic epithelial neoplasms. To accomplish this, a Thymic Domain of the
      Staging and Prognostic Factors Committee (TD-SPFC) was established to formulate
      the rationale, methodology, and definitions of this tumor-node-metastasis (TNM)
      staging system, which is presented in this article. (c) RSNA, 2017.

PMID- 28493799
TI  - Shear-Wave Elastography: Basic Physics and Musculoskeletal Applications.
AB  - In the past 2 decades, sonoelastography has been progressively used as a tool to
      help evaluate soft-tissue elasticity and add to information obtained with
      conventional gray-scale and Doppler ultrasonographic techniques. Recently
      introduced on clinical scanners, shear-wave elastography (SWE) is considered to
      be more objective, quantitative, and reproducible than compression
      sonoelastography with increasing applications to the musculoskeletal system. SWE
      uses an acoustic radiation force pulse sequence to generate shear waves, which
      propagate perpendicular to the ultrasound beam, causing transient displacements.
      The distribution of shear-wave velocities at each pixel is directly related to
      the shear modulus, an absolute measure of the tissue's elastic properties. Shear
      wave images are automatically coregistered with standard B-mode images to provide
      quantitative color elastograms with anatomic specificity. Shear waves propagate
      faster through stiffer contracted tissue, as well as along the long axis of
      tendon and muscle. SWE has a promising role in determining the severity of
      disease and treatment follow-up of various musculoskeletal tissues including
      tendons, muscles, nerves, and ligaments. This article describes the basic
      ultrasound physics of SWE and its applications in the evaluation of various
      traumatic and pathologic conditions of the musculoskeletal system. (c)RSNA, 2017.

PMID- 28493801
TI  - Imaging of Hydatid Disease with a Focus on Extrahepatic Involvement.
AB  - Hydatid disease (HD) is a parasitic infection caused by the larvae of a tapeworm
      that is endemic to many regions around the world-South America, Africa, and Asia,
      in particular. Humans are infected as intermediate hosts in the parasite's life
      cycle; thus, HD can be seen in persons living in areas where animal husbandry is
      practiced. However, owing to the varied patterns of migration and immigration
      during the past several decades, HD can be diagnosed in individuals living
      anywhere. The liver is the most common organ involved, with hepatic HD accounting
      for the majority of published cases. However, HD can affect multiple organs and
      tissues other than the liver, including the spleen, kidneys, lungs, heart,
      peritoneum, muscles, and brain. Knowledge of the route of spread, clinical
      findings at presentation, and possible complications involving each extrahepatic
      location can be useful for the radiologist when evaluating imaging findings in
      patients suspected of having HD. The ultrasonographic, computed tomographic, and
      magnetic resonance imaging findings of extrahepatic hydatid lesions frequently
      simulate those of hepatic HD, as long as rupture, bleeding, and/or superimposed
      bacterial infection has not occurred. Specific features of HD seen at different
      extrahepatic sites can help tailor the diagnosis. The differential diagnoses that
      can mimic HD at every nonhepatic location should be considered, as many of these
      entities are common, especially in nonendemic areas. (c)RSNA, 2017.

PMID- 28493802
TI  - Placental Imaging: Normal Appearance with Review of Pathologic Findings.
AB  - The placenta plays a crucial role throughout pregnancy, and its importance may be
      overlooked during routine antenatal imaging evaluation. Detailed systematic
      assessment of the placenta at ultrasonography (US), the standard imaging
      examination during pregnancy, is important. Familiarity with the normal and
      abnormal imaging appearance of the placenta along with the multimodality and
      methodical approach for evaluation of its related abnormalities is necessary, so
      that radiologists can alert clinicians regarding appropriate prompt management
      decisions. This will potentially decrease fetal and maternal morbidity and
      mortality. This article reviews early placental formation and the expected
      imaging appearance of the placenta during pregnancy, as well as variations in its
      morphology. It also discusses various placental diseases and their potential
      clinical consequences. Placental pathologic conditions include abnormalities of
      placental size, cord insertion, placental and cord location, and placental
      adherence. Other conditions such as bleeding in and around the placenta, as well
      as trophoblastic and nontrophoblastic tumors of the placenta, are also discussed.
      US with Doppler imaging is the initial imaging modality of choice for placental
      evaluation. Magnetic resonance (MR) imaging is reserved for equivocal cases or
      when additional information is needed. Computed tomography (CT) has a limited
      role in evaluation of placental abnormalities because of the ionizing radiation
      exposure and the relatively limited assessment of the placenta; however, CT can
      provide important information in specific circumstances, particularly evaluation
      of trauma and staging of choriocarcinoma. This article also addresses recent
      techniques and updates in placental imaging, including elastography, diffusion
      weighted MR imaging, and blood oxygen level-dependent (BOLD) MR imaging. These
      advanced imaging techniques may provide additional information in evaluation of
      abnormal placental adherence and new insights into placental pathophysiology in
      selected patients. Online supplemental material is available for this article.
      (c)RSNA, 2017.

PMID- 28493803
TI  - Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features,
      Part 2-Uncommon Sarcomas.
AB  - Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but
      important group of malignancies. Recent changes to the World Health Organization
      classification of soft-tissue tumors include the movement of gastrointestinal
      stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the
      most common intraperitoneal sarcoma. Liposarcoma is the most common
      retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST,
      liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered
      in the abdomen and pelvis and are discussed in part 1 of this article.
      Undifferentiated pleomorphic sarcoma (previously called malignant fibrous
      histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant
      peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous
      sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly
      arise in the abdomen and pelvis and the abdominal wall. Although these lesions
      are rare sarcomas and their imaging features overlap, familiarity with the
      locations where they occur and their imaging features is important so they can be
      diagnosed accurately. The anatomic location and clinical history are important
      factors in the differential diagnosis of these lesions because metastasis, more
      common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors),
      and endometriosis have imaging findings that overlap with those of these uncommon
      sarcomas. In this article, the clinical, pathologic, and imaging findings of
      uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall
      are reviewed, with an emphasis on their differential diagnosis.

PMID- 28493804
TI  - Hereditary Renal Cystic Disorders: Imaging of the Kidneys and Beyond.
AB  - The purpose of this article is to review the hereditary renal cystic diseases
      that can manifest in children and adults, with specific attention to pathogenesis
      and imaging features. Various common and uncommon hereditary renal cystic
      diseases are reviewed in terms of their underlying etiology, including the
      involved genetic mutations and the affected proteins and cellular structures.
      Focus is placed on the morphologic findings in each condition and the features
      that distinguish one disorder from another. The two most common categories of
      hereditary renal cystic disease are (a) the ciliopathic disorders, which are
      related to mutations affecting the primary cilia (called "ciliopathies"), and (b)
      the phakomatoses. Autosomal dominant polycystic kidney disease, autosomal
      recessive polycystic kidney disease, and the "medullary cystic disease complex"
      are all ciliopathies but have different phenotypes. Tuberous sclerosis complex
      and the associated "contiguous gene syndrome," as well as von Hippel-Lindau
      syndrome, are phakomatoses that can manifest with cystic renal lesions but have
      uniquely different extrarenal manifestations. Finally, DICER1 mutations can
      manifest with renal cystic lesions (typically, cystic nephromas) in patients
      predisposed to other malignancies in the chest, ovaries, and thyroid. Although
      some overlap exists in the appearance of the renal cysts associated with each of
      these diseases, there are clear morphologic differences (eg, cyst size, location,
      and complexity) that are emphasized in this review. To improve patient outcomes,
      it is important for the radiologist to recognize the various hereditary renal
      cystic diseases so that a correct diagnosis is assigned and so that the patient
      is adequately evaluated and followed up. (c)RSNA, 2017.

PMID- 28493805
TI  - Creating Three-dimensional Printed Models of Acetabular Fractures for Use as
      Educational Tools.
AB  - Acetabular fractures are frequently encountered in some clinical practices, and
      the precise classification of these fractures greatly influences treatments and
      outcomes. The authors identified the need for an educational aid when teaching
      acetabular fracture classifications, given the complex spatial anatomy and the
      nonintuitive classification system that is commonly used. Three-dimensional ( 3D
      three-dimensional ) printing is an evolving technique that has applications as an
      educational aid, providing the student with a tangible object to interact with
      and learn from. In this article, the authors review their experience creating 3D
      three-dimensional printed models of the hip for educational purposes. Their goal
      was to create 3D three-dimensional printed models for use as educational aids
      when teaching acetabular fracture classifications. Complex cases involving a
      combination of fracture types, subtle nondisplaced fractures, and/or fractures
      with associated osteopenia or artifacts were excluded. The selected computed
      tomographic (CT) scans were loaded into a medical 3D three-dimensional volume
      rendering program, and a 3D three-dimensional volumetric model was created.
      Standard Tessellation Language ( STL Standard Tessellation Language ) files were
      then exported to STL Standard Tessellation Language model-editing software and
      edited to retain only the involved hemipelvis. In some cases, the proximal femur
      and ipsilateral hemisacrum may be included to emphasize hip alignment or
      disruption of the force transfer. Displaced fracture fragments can be printed as
      separate segments or a single unit after the addition of struts. Printing was
      performed by using an additive manufacturing principle, with approximately 36-48
      hours needed for printing, postprocessing, and drying. The cost to print a 1:1
      scale model was approximately $100-$200, depending on the amount of plastic
      material used. These models can then be painted according to the two-column
      theory regarding acetabular fractures. (c)RSNA, 2017.

PMID- 28493806
TI  - Pediatric Benign Bone Tumors: What Does the Radiologist Need to Know?: Pediatric
      Imaging.

PMID- 28493807
TI  - What Is Actually Affected by the Scrambling of Objects When Localizing the
      Lateral Occipital Complex?
AB  - The lateral occipital complex (LOC), the cortical region critical for shape
      perception, is localized with fMRI by its greater BOLD activity when viewing
      intact objects compared with their scrambled versions (resembling texture).
      Despite hundreds of studies investigating LOC, what the LOC localizer
      accomplishes-beyond distinguishing shape from texture-has never been resolved. By
      independently scattering the intact parts of objects, the axis structure defining
      the relations between parts was no longer defined. This led to a diminished BOLD
      response, despite the increase in the number of independent entities (the parts)
      produced by the scattering, thus indicating that LOC specifies interpart
      relations, in addition to specifying the shape of the parts themselves. LOC's
      sensitivity to relations is not confined to those between parts but is also
      readily apparent between objects, rendering it-and not subsequent "place" areas
      as the critical region for the representation of scenes. Moreover, that these
      effects are witnessed with novel as well as familiar intact objects and scenes
      suggests that the relations are computed on the fly, rather than being retrieved
      from memory.

PMID- 28493808
TI  - Prestimulus Alpha Oscillations and the Temporal Sequencing of Audiovisual Events.
AB  - Perceiving the temporal order of sensory events typically depends on
      participants' attentional state, thus likely on the endogenous fluctuations of
      brain activity. Using magnetoencephalography, we sought to determine whether
      spontaneous brain oscillations could disambiguate the perceived order of auditory
      and visual events presented in close temporal proximity, that is, at the
      individual's perceptual order threshold (Point of Subjective Simultaneity [PSS]).
      Two neural responses were found to index an individual's temporal order
      perception when contrasting brain activity as a function of perceived order
      (i.e., perceiving the sound first vs. perceiving the visual event first) given
      the same physical audiovisual sequence. First, average differences in prestimulus
      auditory alpha power indicated perceiving the correct ordering of audiovisual
      events irrespective of which sensory modality came first: a relatively low alpha
      power indicated perceiving auditory or visual first as a function of the actual
      sequence order. Additionally, the relative changes in the amplitude of the
      auditory (but not visual) evoked responses were correlated with participant's
      correct performance. Crucially, the sign of the magnitude difference in
      prestimulus alpha power and evoked responses between perceived audiovisual orders
      correlated with an individual's PSS. Taken together, our results suggest that
      spontaneous oscillatory activity cannot disambiguate subjective temporal order
      without prior knowledge of the individual's bias toward perceiving one or the
      other sensory modality first. Altogether, our results suggest that, under high
      perceptual uncertainty, the magnitude of prestimulus alpha (de)synchronization
      indicates the amount of compensation needed to overcome an individual's prior in
      the serial ordering and temporal sequencing of information.

PMID- 28493809
TI  - Buildings, Beauty, and the Brain: A Neuroscience of Architectural Experience.
AB  - A burgeoning interest in the intersection of neuroscience and architecture
      promises to offer biologically inspired insights into the design of spaces. The
      goal of such interdisciplinary approaches to architecture is to motivate
      construction of environments that would contribute to peoples' flourishing in
      behavior, health, and well-being. We suggest that this nascent field of
      neuroarchitecture is at a pivotal point in which neuroscience and architecture
      are poised to extend to a neuroscience of architecture. In such a research
      program, architectural experiences themselves are the target of neuroscientific
      inquiry. Here, we draw lessons from recent developments in neuroaesthetics to
      suggest how neuroarchitecture might mature into an experimental science. We
      review the extant literature and offer an initial framework from which to
      contextualize such research. Finally, we outline theoretical and technical
      challenges that lie ahead.

PMID- 28493810
TI  - Rapid Statistical Learning Supporting Word Extraction From Continuous Speech.
AB  - The identification of words in continuous speech, known as speech segmentation,
      is a critical early step in language acquisition. This process is partially
      supported by statistical learning, the ability to extract patterns from the
      environment. Given that speech segmentation represents a potential bottleneck for
      language acquisition, patterns in speech may be extracted very rapidly, without
      extensive exposure. This hypothesis was examined by exposing participants to
      continuous speech streams composed of novel repeating nonsense words. Learning
      was measured on-line using a reaction time task. After merely one exposure to an
      embedded novel word, learners demonstrated significant learning effects, as
      revealed by faster responses to predictable than to unpredictable syllables.
      These results demonstrate that learners gained sensitivity to the statistical
      structure of unfamiliar speech on a very rapid timescale. This ability may play
      an essential role in early stages of language acquisition, allowing learners to
      rapidly identify word candidates and "break in" to an unfamiliar language.

PMID- 28493811
TI  - Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for
      Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger
      Patients Who Participated in US National Cancer Institute Cooperative Group
      Studies.
AB  - Purpose Concurrent chemoradiotherapy is standard treatment for patients with
      stage III non-small-cell lung cancer. Elderly patients may experience increased
      rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy.
      Patients and Methods Individual patient data were collected from 16 phase II or
      III trials conducted by US National Cancer Institute-supported cooperative groups
      of concurrent chemoradiotherapy alone or with consolidation or induction
      chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall
      survival (OS), progression-free survival, and AEs were compared between patients
      age >= 70 (elderly) and those younger than 70 years (younger). Unadjusted and
      adjusted hazard ratios (HRs) for survival time and CIs were estimated by single
      predictor and multivariable frailty Cox models. Unadjusted and adjusted odds
      ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable
      generalized linear mixed-effect models. Results A total of 2,768 patients were
      classified as younger and 832 as elderly. In unadjusted and multivariable models,
      elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95%
      CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly
      and younger patients had similar progression-free survival (HR, 1.01; 95% CI,
      0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients
      had a higher rate of grade >= 3 AEs in unadjusted and multivariable models (OR,
      1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively).
      Grade 5 AEs were significantly higher in elderly compared with younger patients
      (9% v 4%; P < .01). Fewer elderly compared with younger patients completed
      treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs
      (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused
      further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in
      concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had
      a higher rate of death during treatment than younger patients.

PMID- 28493813
TI  - Further Advances in the Management of Anaplastic Lymphoma Kinase-Mutated Non
      Small-Cell Lung Cancer.

PMID- 28493814
TI  - Obesity and Modifiable Cardiovascular Disease Risk Factors Among Chinese
      Americans in New York City, 2009-2012.
AB  - We used the Racial and Ethnic Approaches to Community Health Across the US (REACH
      US) Risk Factor Survey from 2009 through 2012 to examine the association between
      body mass index (BMI, calculated as kg/m2) and 3 cardiovascular disease risk
      factors among Chinese Americans in New York City. We used traditional BMI cut
      points and cut points modified for the Asian population. Compared with
      normal/underweight Chinese American adults (BMI <23.0), obese Chinese American
      adults (BMI >=27.5) had significantly higher odds of having each risk factor in
      fully adjusted logistic regression models: diabetes (odds ratio [OR], 4.2; 95%
      confidence interval [CI], 2.8-6.2), high blood pressure (OR, 5.5; 95% CI, 3.9
      7.7), and high cholesterol (OR, 1.7; 95% CI, 1.2-2.4). Regression results were
      similar across BMI definitions, suggesting that both BMI categorizations should
      be considered in CVD research among Chinese Americans.

PMID- 28493815
TI  - The biology of JC polyomavirus.
AB  - JC polyomavirus (JCPyV) is the causative agent of a fatal central nervous system
      demyelinating disease known as progressive multifocal leukoencephalopathy (PML).
      PML occurs in people with underlying immunodeficiency or in individuals being
      treated with potent immunomodulatory therapies. JCPyV is a DNA tumor virus with a
      double-stranded DNA genome and encodes a well-studied oncogene, large T antigen.
      Its host range is highly restricted to humans and only a few cell types support
      lytic infection in vivo or in vitro. Its oncogenic potential in humans has not
      been firmly established and the international committee on oncogenic viruses
      lists JCPyV as possibly carcinogenic. Significant progress has been made in
      understanding the biology of JCPyV and here we present an overview of the field
      and discuss some important questions that remain unanswered.

PMID- 28493812
TI  - Treatment Decision Regret Among Long-Term Survivors of Localized Prostate Cancer:
      Results From the Prostate Cancer Outcomes Study.
AB  - Purpose To determine the demographic, clinical, decision-making, and quality-of
      life factors that are associated with treatment decision regret among long-term
      survivors of localized prostate cancer. Patients and Methods We evaluated men who
      were age <= 75 years when diagnosed with localized prostate cancer between
      October 1994 and October 1995 in one of six SEER tumor registries and who
      completed a 15-year follow-up survey. The survey obtained demographic,
      socioeconomic, and clinical data and measured treatment decision regret, informed
      decision making, general- and disease-specific quality of life, health worry,
      prostate-specific antigen (PSA) concern, and outlook on life. We used
      multivariable logistic regression analyses to identify factors associated with
      regret. Results We surveyed 934 participants, 69.3% of known survivors. Among the
      cohort, 59.1% had low-risk tumor characteristics (PSA < 10 ng/mL and Gleason
      score < 7), and 89.2% underwent active treatment. Overall, 14.6% expressed
      treatment decision regret: 8.2% of those whose disease was managed
      conservatively, 15.0% of those who received surgery, and 16.6% of those who
      underwent radiotherapy. Factors associated with regret on multivariable analysis
      included reporting moderate or big sexual function bother (reported by 39.0%; OR,
      2.77; 95% CI, 1.51 to 5.0), moderate or big bowel function bother (reported by
      7.7%; OR, 2.32; 95% CI, 1.04 to 5.15), and PSA concern (mean score 52.8; OR, 1.01
      per point change; 95% CI, 1.00 to 1.02). Increasing age at diagnosis and report
      of having made an informed treatment decision were inversely associated with
      regret. Conclusion Regret was a relatively infrequently reported outcome among
      long-term survivors of localized prostate cancer; however, our results suggest
      that better informing men about treatment options, in particular, conservative
      treatment, might help mitigate long-term regret. These findings are timely for
      men with low-risk cancers who are being encouraged to consider active
      surveillance.

PMID- 28493816
TI  - Sample types applied for molecular diagnosis of therapeutic management of
      advanced non-small cell lung cancer in the precision medicine.
AB  - In this era of precision medicine, molecular biology is becoming increasingly
      significant for the diagnosis and therapeutic management of non-small cell lung
      cancer. The specimen as the primary element of the whole testing flow is
      particularly important for maintaining the accuracy of gene alteration testing.
      Presently, the main sample types applied in routine diagnosis are tissue and
      cytology biopsies. Liquid biopsies are considered as the most promising
      alternatives when tissue and cytology samples are not available. Each sample type
      possesses its own strengths and weaknesses, pertaining to the disparity of
      sampling, preparation and preservation procedures, the heterogeneity of inter- or
      intratumors, the tumor cellularity (percentage and number of tumor cells) of
      specimens, etc., and none of them can individually be a "one size to fit all".
      Therefore, in this review, we summarized the strengths and weaknesses of
      different sample types that are widely used in clinical practice, offered
      solutions to reduce the negative impact of the samples and proposed an optimized
      strategy for choice of samples during the entire diagnostic course. We hope to
      provide valuable information to laboratories for choosing optimal clinical
      specimens to achieve comprehensive functional genomic landscapes and formulate
      individually tailored treatment plans for NSCLC patients that are in advanced
      stages.

PMID- 28493817
TI  - The relationship between anxiety, depression and risk behaviors in adolescents.
AB  - Aim Adolescence is a developmental period often associated with high-risk
      behaviors. While some risk-taking behavior is considered normative in
      adolescents, research has indicated an association between risky behaviors and
      mental ill-health. The current research aimed to examine the relationship between
      anxiety and depression with the occurrence of high-risk behaviors in adolescents
      and also determine the predictive factors of these main variables. Methods A
      descriptive, cross-sectional, correlational design was used to collect data from
      399 adolescents between the ages of 14 and 19 residing in Qazvin, Iran using the
      Revised Child Anxiety and Depression Scale (RCADS) and the Iranian Adolescents
      Risk-taking Scale (IARS) between the period of October and November 2015. Data
      analysis included descriptive and inferential statistics powered by SPSS (v. 23).
      Results Mean scores for anxiety, depression and risky behaviors were 37.70 +/-
      21.11 and 80.76 +/- 31.30, respectively. Participants' frequency of suicidal
      thoughts (beta = 0.126, p < 0.05) positively predicted anxiety and depression,
      while age (beta = -0.126, p < 0.01) and self-confidence (beta = -0.307, p <
      0.001) negatively predicted anxiety and depression. Moreover, having friends that
      smoke (beta = 0.366, p < 0.001), suicidal thoughts (beta = 0.127, p < 0.01), and
      the strength of suicidal thoughts (beta = 0.100, p < 0.05) were positive
      predictors of occurrence of risky behaviors. Furthermore, religious belief (beta
      = -0.204, p < 0.001) negatively predicted occurrence of risky behaviors in
      Iranian adolescents. Male respondents were more likely to have higher level of
      occurrence of risky behaviors than females (beta = -0.193, p < 0.001). Conclusion
      Findings of the present study suggest that anxiety and depression positively and
      significantly predict the occurrence of risky behaviors in addition to having
      friends that smoke, suicidal thoughts, and strong suicidal thinking. The
      implications of these findings have relevance for screening, prevention, and
      treatment interventions targeting mental health in adolescents.

PMID- 28493818
TI  - Group Tests for High-dimensional Failure Time Data with the Additive Hazards
      Models.
AB  - Statistical analysis of high-dimensional data has been attracting more and more
      attention due to the abundance of such data in various fields such as genetic
      studies or genomics and the existence of many interesting topics. Among them, one
      is the identification of a gene or genes that have significant effects on the
      occurrence of or are significantly related to a certain disease. In this paper,
      we will discuss such a problem that can be formulated as a group test or testing
      a group of variables or coefficients when one faces right-censored failure time
      response variable. For the problem, we develop a corrected variance reduced
      partial profiling (CVRPP) linear regression model and a likelihood ratio test
      procedure when the failure time of interest follows the additive hazards model.
      The numerical study suggests that the proposed method works well in practical
      situations and gives better performance than the existing one. An illustrative
      example is provided.

PMID- 28493819
TI  - The choice of freely preferred cadence by trained nonprofessional cyclists may
      not be characterized by mechanical efficiency.
AB  - BACKGROUND: Most cycling studies involve professional cyclists. Because training
      may affect riding style, it is of interest to determine the physiological basis
      for the personal choice of cycling cadence in nonprofessional cyclists. METHODS:
      Eleven nonprofessional (5.2+/-1.7-year-riding experience) male road cyclists,
      aged 35.0+/-11.0 years, underwent four separate laboratory test sessions. The
      first two sessions included habituation, anthropometry, VO2max,$?dot
      V{{?text{O}}_{?text{2}}}{?text{max}},$ and lactate threshold (LaTH) measurements.
      Freely preferred cadence at LaTH was determined during the second session (mean+/
      SD=94.7+/-2.9 rev.min-1). During the third and fourth sessions participants
      performed LaTH tests at 60 and 95 rev.min-1 in a randomized order, with power
      output (PO) increments of 25 W every 4 min, up to ~90% of VO2max.$?dot
      V{{?text{O}}_{?text{2}}}{?text{max}}{?text{.}}$ Results: VO2,$?dot
      V{{?text{O}}_{?text{2}}},$ expired ventilation (VE),$({?dot V_E}),$ blood lactate
      (La), and calculated net mechanical efficiency (MEnet) rose with increased PO. At
      95 rev.min-1, VO2, VE,$?dot V{{?text{O}}_2},{?text{ }}{?dot V_{?text{E}}},$ and
      La were significantly higher than at 60 rev.min-1 at all POs. MEnet at 95 rev.min
      1 was lower than at 60 rev.min-1. Mean PO attained at LaTh did not differ
      significantly between 60 and 95 rev.min-1 (220.9+/-29.0 and 214.5+/-9.2 W,
      respectively). La values at LaTH were higher at 95 rev.min-1 than at 60 rev.min-1
      (3.01+/-0.17 vs. 2.10+/-0.13 mM, p<0.05, respectively). CONCLUSIONS: Our findings
      indicate that mechanical and physiological efficiencies may not determine the
      choice of cycling cadence by nonprofessional cyclists. This choice may reflect
      the need to maintain endurance at the expense of riding at a lower than optimal
      riding efficiency.

PMID- 28493820
TI  - Deoxyguanosine kinase deficiency: a report of four patients.
AB  - BACKGROUND: Hepatic involvement is a common feature in childhood mitochondrial
      disorders. Deoxyguanosine kinase (DGUOK) deficiency is one of the mitochondrial
      DNA depletion syndromes associated with hepatocerebral syndrome. Hepatic disease
      and neurologic dysfunction occurs within weeks after birth. Low birth weight is
      one of the common features. This study aims to describe the clinical and
      laboratory features of four infants carrying four different pathogenic variants
      in the DGUOK gene. CASE PRESENTATION: Common clinical findings were progressive
      cholestatic liver failure, hypoglycemia, hypotonia and rotatory nystagmus in our
      DGUOK deficiency patients. Lactic acidosis, elevated serum tyrosine and ferritin
      levels were the striking laboratory features. Cholestasis, iron deposits,
      microvesicular steatosis and fibrosis were the histopathological findings seen in
      liver biopsies of two patients. All patients died with multi-organ failure
      between the ages of 42 days and 6 months. CONCLUSIONS: While neurologic findings
      may occur later in the course of the disease, elevated serum tyrosine levels may
      alert the physicians to a DGUOK deficiency in a baby with hepatopathy in the
      presence of the mentioned signs. Early diagnosis is important not only for
      genetic counseling but also for a possible liver transplantation.

PMID- 28493821
TI  - Multicentric studies of the fetal neurobehavior by KANET test.
AB  - Assessment of fetal neurobehavior and detection of neurological impairment
      prenatally has been a great challenge in perinatal medicine. The evolution of
      four-dimensional (4D) ultrasound not only enabled a better visualization of fetal
      anatomy but also allowed the study of fetal behavior in real time. Kurjak
      Antenatal Neurodevelopmental Test (KANET) was developed for the assessment of
      fetal neurobehavior and the detection of neurological disorders, based on the
      assessment of the fetus by application of 4D ultrasound in the same way that a
      neonate is assessed postnatally. KANET is a method that has been applied for the
      past 10 years and studies show that it is a strong diagnostic tool and can be
      introduced into everyday clinical practice. We present all data from studies
      performed up to now on KANET.

PMID- 28493822
TI  - Diagnosis of fetal syndromes by three- and four-dimensional ultrasound: is there
      any improvement?
AB  - With all of our present knowledge, high technology diagnostic equipment,
      electronic databases and other available supporting resources, detection of fetal
      syndromes is still a challenge for healthcare providers in prenatal as well as in
      the postnatal period. Prenatal diagnosis of fetal syndromes is not
      straightforward, and it is a difficult puzzle that needs to be assembled and
      solved. Detection of one anomaly should always raise a suspicion of the existence
      of more anomalies, and can be a trigger to investigate further and raise
      awareness of possible syndromes. Highly specialized software systems for three-
      and four-dimensional ultrasound (3D/4D US) enabled detailed depiction of fetal
      anatomy and assessment of the dynamics of fetal structural and functional
      development in real time. With recent advances in 3D/4D US technology, antenatal
      diagnosis of fetal anomalies and syndromes shifted from the 2nd to the 1st
      trimester of pregnancy. It is questionable what can and should be done after the
      prenatal diagnosis of fetal syndrome. The 3D and 4D US techniques improved
      detection accuracy of fetal abnormalities and syndromes from early pregnancy
      onwards. It is not easy to make prenatal diagnosis of fetal syndromes, so tools
      which help like online integrated databases are needed to increase diagnostic
      precision. The aim of this paper is to present the possibilities of different US
      techniques in the detection of some fetal syndromes prenatally.

PMID- 28493848
TI  - Investigating multi-objective fluence and beam orientation IMRT optimization.
AB  - Radiation Oncology treatment planning requires compromises to be made between
      clinical objectives that are invariably in conflict. It would be beneficial to
      have a 'bird's-eye-view' perspective of the full spectrum of treatment plans that
      represent the possible trade-offs between delivering the intended dose to the
      planning target volume (PTV) while optimally sparing the organs-at-risk (OARs).
      In this work, the authors demonstrate Pareto-aware radiotherapy evolutionary
      treatment optimization (PARETO), a multi-objective tool featuring such bird's-eye
      view functionality, which optimizes fluence patterns and beam angles for
      intensity-modulated radiation therapy (IMRT) treatment planning. The problem of
      IMRT treatment plan optimization is managed as a combined monolithic problem,
      where all beam fluence and angle parameters are treated equally during the
      optimization. To achieve this, PARETO is built around a powerful multi-objective
      evolutionary algorithm, called Ferret, which simultaneously optimizes multiple
      fitness functions that encode the attributes of the desired dose distribution for
      the PTV and OARs. The graphical interfaces within PARETO provide useful
      information such as: the convergence behavior during optimization, trade-off
      plots between the competing objectives, and a graphical representation of the
      optimal solution database allowing for the rapid exploration of treatment plan
      quality through the evaluation of dose-volume histograms and isodose
      distributions. PARETO was evaluated for two relatively complex clinical cases, a
      paranasal sinus and a pancreas case. The end result of each PARETO run was a
      database of optimal (non-dominated) treatment plans that demonstrated trade-offs
      between the OAR and PTV fitness functions, which were all equally good in the
      Pareto-optimal sense (where no one objective can be improved without worsening at
      least one other). Ferret was able to produce high quality solutions even though a
      large number of parameters, such as beam fluence and beam angles, were included
      in the optimization.

PMID- 28493839
TI  - Hypoxia inducible factors in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is one of the most prevalent and lethal cancers with
      limited therapeutic options. Pathogenesis of this disease involves tumor hypoxia
      and the activation of hypoxia inducible factors. In this review, we describe the
      current understanding of hypoxia signaling pathway and summarize the expression,
      function and target genes of hypoxia inducible factors in hepatocellular
      carcinoma. We also highlight the recent progress in hypoxia-targeted therapeutic
      strategies in hepatocellular carcinoma and discuss further the future efforts for
      the study of hypoxia and/or hypoxia inducible factors in this deadly disease.

PMID- 28493842
TI  - Mesenchymal stem cell infiltration during neoplastic transformation of the human
      prostate.
AB  - Mesenchymal Stem Cells (MSCs) have been identified in prostate cancer, raising
      the critical question of their physical and temporal source. Therefore, MSCs were
      quantified and characterized in benign and malignant prostate tissue representing
      different disease states and a wide range of age groups from fetal development
      through adult death using analytical and functional methodologies. In contrast to
      lineage-restricted Mesenchymal Progenitor Cells (MPCs) found in normal prostate
      tissue, MSCs with tri-lineage differentiation potential (adipogenesis,
      osteogenesis, and chondrogenesis) are identified in prostate tissue from a subset
      of men with prostate cancer, consistent with an influx of more stem-like
      progenitors (i.e. MSCs) from the bone marrow. Additionally, prostate tissue from
      a subset of these patients is highly enriched in MSCs, suggesting their
      enumeration may have prognostic value for identifying men with aggressive
      disease. This influx is an ongoing process continuing throughout disease
      progression as documented by the presence of MSCs in metastatic lesions from
      multiple organ sites harvested at the time of death in metastatic castration
      resistant prostate cancer (mCRPC) patients. This infiltration of MSCs from
      systemic circulation provides the rationale for their use as a cell-based vector
      to deliver therapeutic agents.

PMID- 28493849
TI  - Effects of pressure variation and atrial fibrillation on CardioMEMSTM HF measured
      pulmonary artery diastolic pressure: comparison of device-averaged and visually
      inspected waveforms.
AB  - OBJECTIVE: Heart failure (HF) management guided by implantable hemodynamic
      monitoring reduces hospitalization rates. Hemodynamic data from the CardioMEMSTM
      HF system includes device-averaged pulmonary artery pressures (PAP) and heart
      rate. Agreement of device-averaged values compared to the standard method of
      visual inspection of pressure waveforms at end-expiration is unknown. We
      evaluated the agreement between device-averaged and visually inspected end
      expiratory PAP. APPROACH: Twenty-one patients implanted with the CardioMEMSTM HF
      system were evaluated. Eight-hundred twenty-three PAP waveforms from the Merlin
      remote monitoring website were visually inspected and pulmonary artery systolic
      pressure (PASP) and pulmonary artery diastolic pressure (PADP) at end-expiration
      were recorded. Waveforms were evaluated for pressure variation (PV), defined as
      the difference between highest and lowest PASP measurement of  ?20 mmHg. Bland
      Altman analysis quantified differences between device-averaged and visually
      inspected waveforms. MAIN RESULTS: All patients were NYHA functional class III,
      mean age was 67  +/-  15 years and 15 (71%) had AF. Bland-Altman analysis of all
      waveforms revealed a mean-difference in PADP of  -1.4 mmHg, indicating that
      visually inspected values were higher than device-averaged values. For PV  ?20
      mmHg, this value increased to  -2.8 mmHg. The mean-difference comparing waveforms
      from patients with or without AF was  -1.3 and  -1.6 mmHg, respectively. The 95%
      limits of agreement were  >50% wider for waveforms from patients with versus
      without AF (10.3 versus 6.7 mmHg). SIGNIFICANCE: There is good agreement between
      device-averaged and visually inspected waveforms when pressure variation is  <20
      mmHg and for patients without atrial fibrillation.

PMID- 28493850
TI  - Importance of endogenous extracellular matrix in biomechanical properties of
      human skin model.
AB  - The physical and mechanical properties of cells modulate their behavior such
      proliferation rate, migration and extracellular matrix remodeling. In order to
      study cell behavior in a tissue-like environment in vitro, it is of utmost
      importance to develop biologically and physically relevant 3D cell models. Here,
      we characterized the physical properties of a single cell type growing in
      configurations of increasing complexity. From one human skin biopsy, primary
      dermal fibroblasts were isolated and seeded to give monolayer (2D model),
      spheroid (3D model poor in extracellular matrix) and tissue-engineered cell sheet
      (3D model rich in endogenous extracellular matrix). Living native human dermis
      tissue was used as a gold standard. Nanomechanical and viscoelastic properties at
      the cell scale were measured by atomic force microscopy (AFM) while biphoton
      microscopy allowed collagen detection by second harmonic generation and scanning
      electron microscopy helped in model morphological characterization. In all
      models, fibroblasts presented a similar typical elongated cell shape, with a
      cytoskeleton well-arranged along the long axis of the cell. However, elastic
      moduli of the tissue-engineered cell sheet and native dermis tissue were similar
      and statistically lower than monolayer and spheroid models. We successfully
      carried out AFM force measurements on 3D models such as spheroids and tissue
      engineered cell sheets, as well as on living native human tissue. We demonstrated
      that a tissue-engineered dermal model recapitulates the mechanical properties of
      human native dermal tissue unlike the classically used monolayer and spheroid
      models. Furthermore, we give statistical evidence to indicate a correlation
      between cell mechanical properties and the presence of collagens in the models
      studied.

PMID- 28493852
TI  - Notes from the Field: Severe Human Metapneumovirus Infections - North Dakota,
      2016.

PMID- 28493851
TI  - Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on
      Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines.
AB  - BACKGROUND Experiments on porcine heart scaffold represent significant assays in
      development of immunoneutral materials for cardiac surgery. Characterization of
      cell-cell and cell-scaffold interactions is essential to understand the homing
      process of cardiac cells into the scaffolds. MATERIAL AND METHODS In the present
      study, the highly sensitive and real-time impedimetric technique of xCELLigence
      SP was used to monitor cell adhesion, which is the key process of
      recellularization in heart scaffolds. Our objectives were: (i) to characterize
      the effect of decellularized porcine heart scaffold on cell adhesion of human
      cardiovascular cells potentially used in the recellularization process; and (ii)
      to investigate cell-extracellular matrix element interactions for building
      artificial multi-layer systems, applied as cellular models of recellularization
      experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were
      investigated and the effect of decellularized porcine heart scaffold (HS) and
      fibronectin on cell adhesion was examined. Adhesion was quantified as slope of
      curves. RESULTS Heart scaffold had neutral effect on cardiomyocytes as well as on
      endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin
      (1.480+/-0.021) compared to control (0.745+/-0.029). The combination of
      fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407+/-0.634)
      than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly
      strong adhesion profiles with marked enhancer effect by fibronectin. CONCLUSIONS
      Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells
      at the cell biological level, while fibronectin has strong cell adhesion-inducer
      effect, as well as an enhancer effect on activity of HS. Consequently,
      decellularized porcine hearts could be used as scaffolds for recellularization
      with cardiomyocytes and endothelial cells with fibronectin acting as a regulator,
      leading to construction of working bioartificial hearts.

PMID- 28493853
TI  - Erratum: Vol. 66, No. 17.
AB  - In the report "Vital Signs: Racial Disparities in Age-Specific Mortality Among
      Blacks or African Americans - United States, 1999-2015," on page 446, under
      "Results," the last sentence of the first paragraph should have read "Among
      adults aged >=65 years, the death rate in 2015 relative to that in 1999 declined
      27% for blacks and 17% for whites, resulting in a crossover in death rates after
      2010, when blacks had lower age-specific death rates than whites."

PMID- 28493855
TI  - Announcement: Community Preventive Services Task Force Recommendation for Family
      Based Interventions to Increase Physical Activity.
AB  - The Community Preventive Services Task Force recently posted new information on
      its website: "Physical Activity: Family-Based Interventions." This information is
      available at https://www.thecommunityguide.org/findings/physical-activity-family
      based-interventions.

PMID- 28493854
TI  - State HCV Incidence and Policies Related to HCV Preventive and Treatment Services
      for Persons Who Inject Drugs - United States, 2015-2016.
AB  - Hepatitis C is associated with more deaths in the United States than 60 other
      infectious diseases reported to CDC combined. Despite curative hepatitis C virus
      (HCV) therapies and known preventive measures to interrupt transmission, new HCV
      infections have increased in recent years (1,2). Injection drug use is the
      primary risk factor for new HCV infections (2). One potential strategy to
      decrease the prevalence of HCV is to create and strengthen public health laws and
      policies aimed specifically at reducing transmission risks among persons who
      inject drugs. To evaluate factors affecting access to HCV preventive and
      treatment services, CDC assessed state laws governing access to safe injection
      equipment and Medicaid policies related to sobriety requirements for approval of
      HCV treatment for persons who inject drugs. Acute HCV incidence rates were
      obtained from CDC's National Notifiable Disease Surveillance System (NNDSS).
      States were categorized based on analysis of laws related to access to clean
      needles and syringes and Medicaid HCV treatment policies associated with sobriety
      requirements. In 2015, HCV incidence remained high in the United States, with
      rates in 17 states exceeding the national average. Three states were determined
      to have state laws and Medicaid policies capable of comprehensively preventing
      and treating HCV among persons who inject drugs. Opportunities exist for states
      to adopt laws and policies that could help increase access to HCV preventive and
      treatment services reducing the number of persons at risk for HCV transmission
      and disease.

PMID- 28493856
TI  - CDC Grand Rounds: Public Health Strategies to Prevent and Treat Strokes.
AB  - Worldwide, stroke is the second leading cause of death and a leading cause of
      serious long-term disability. In the United States, nearly 800,000 strokes occur
      each year; thus stroke is the fifth leading cause of death overall and the fourth
      leading cause of death among women (1). Major advances in stroke prevention
      through treatment of known risk factors has led to stroke being considered
      largely preventable. For example, in the United States, stroke mortality rates
      have declined 70% over the past 50 years, in large part because of important
      reductions in hypertension, tobacco smoking, and more recently, increased use of
      anticoagulation for atrial fibrillation (2,3). Although the reduction in stroke
      mortality is recognized as one of the 10 great public health achievements of the
      20th century (4), gains can still be made. Approximately 80% of strokes could be
      prevented by screening for and addressing known risks with measures such as
      improving hypertension control, smoking cessation, diabetes prevention,
      cholesterol management, increasing use of anticoagulation for atrial
      fibrillation, and eliminating excessive alcohol consumption (5,6).

PMID- 28493858
TI  - QuickStats: Age-Adjusted Death Rates* Attributable to Alcohol-Induced Causes,? by
      Race/Ethnicity - United States, 1999-2015.
AB  - In 2015, mortality from alcohol-induced causes reached the highest rate during
      1999-2015 of 9.1 deaths per 100,000 U.S. standard population. Alcohol-induced
      death rates for the Hispanic population remained the highest (9.9 per 100,000
      U.S. standard population), followed by the non-Hispanic white population (9.6).
      For the non-Hispanic black population, the alcohol-induced death rate decreased
      33% from 1999 to 2015, while the rate increased by 50% during the same period for
      the non-Hispanic white population. Overall, from 1999 to 2015, mortality from
      alcohol-induced causes increased 28% (7.1 to 9.1).

PMID- 28493857
TI  - Current and Binge Drinking Among High School Students - United States, 1991-2015.
AB  - Excessive drinking accounted for approximately 4,300 deaths each year among
      persons aged <21 years during 2006-2010,* and underage drinking cost the United
      States $24.3 billion in 2010 (1). CDC analyzed data from the national Youth Risk
      Behavior Survey (YRBS) for the years 1991-2015 to examine trends in drinking by
      U.S. high school students, and from the 2015 YRBS to assess the usual source of
      alcohol consumed? and binge drinking intensity (i.e., the average number of
      drinks consumed per binge drinking occasion).S During 1991-2007, the prevalence
      of current drinking  among high school students declined significantly, from
      50.8% (1991) to 44.7% (2007), and then significantly declined to 32.8% in 2015.
      The prevalence of binge drinking** increased from 31.3% in 1991 to 31.5% in 1999,
      and then significantly declined to 17.7% in 2015. Most high school students who
      drank were binge drinkers (57.8%), and 43.8% of binge drinkers consumed eight or
      more drinks in a row. Despite progress, current drinking and binge drinking are
      common among high school students, and many students who binge drink do so at
      high intensity (i.e., eight or more drinks in a row). Widespread use of evidence
      based strategies for preventing excessive drinking (e.g., increasing alcohol
      taxes, regulating alcohol outlet density, and having commercial host liability
      laws) could help reduce underage drinking and related harms.??.

PMID- 28493859
TI  - Recommendations of the Advisory Committee on Immunization Practices for Use of
      Cholera Vaccine.
AB  - Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup
      O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can
      be severe and rapidly fatal without prompt rehydration. Cholera is endemic in
      approximately 60 countries and causes epidemics as well. Globally, cholera
      results in an estimated 2.9 million cases of disease and 95,000 deaths annually
      (1). Cholera is rare in the United States, and most U.S. cases occur among
      travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases
      were reported in 2011 after a cholera epidemic began in Haiti (2); however, <25
      cases per year have been reported in the United States since 2012.

PMID- 28493860
TI  - Hepatitis C Virus Infection Among Women Giving Birth - Tennessee and United
      States, 2009-2014.
AB  - Hepatitis C virus (HCV) affects an estimated 3.5 million persons in the United
      States (1), making it the most common bloodborne infection in the country. Recent
      surveillance data showed increased rates of HCV infection among adolescents and
      adults who are predominantly white, live in nonurban areas, and have a history of
      injection drug use.* U.S. birth certificate data were used to analyze trends and
      geographic variations in rates of HCV infection among women giving birth during
      2009-2014. Birth certificates from Tennessee were used to examine individual
      characteristics and outcomes associated with HCV infection, using a multivariable
      model to calculate adjusted odds of HCV-related diagnosis in pregnancy among
      women with live births. During 2009-2014, HCV infection present at the time of
      delivery among pregnant women from states reporting HCV on the birth certificate
      increased 89%, from 1.8 to 3.4 per 1,000 live births. The highest infection rate
      in 2014 (22.6 per 1,000 live births) was in West Virginia; the rate in Tennessee
      was 10.1. In adjusted analyses of Tennessee births, the odds of HCV infection
      were approximately threefold higher among women residing in rural counties than
      among those in large urban counties, 4.5-fold higher among women who smoked
      cigarettes during pregnancy, and nearly 17-fold higher among women with
      concurrent hepatitis B virus (HBV) infection. HCV infection among pregnant women
      is an increasing and potentially modifiable threat to maternal and child health.
      Clinicians and public health officials should consider individual and population
      level opportunities for prevention and risk mitigation.

PMID- 28493861
TI  - Maternal pre-pregnancy obesity and neuropsychological development in pre-school
      children: a prospective cohort study.
AB  - BackgroundMaternal pre-pregnancy obesity may impair infant neuropsychological
      development, but it is unclear whether intrauterine or confounding factors drive
      this association.MethodsWe assessed whether maternal pre-pregnancy obesity was
      associated with neuropsychological development in 1,827 Spanish children. At 5
      years, cognitive and psychomotor development was assessed using McCarthy Scales
      of Children's Abilities, attention deficit hyperactivity disorder (ADHD) symptoms
      using the Criteria of Diagnostic and Statistical Manual of Mental Disorders, and
      autism spectrum disorder symptoms using the Childhood Asperger Syndrome Test.
      Models were adjusted for sociodemographic factors and maternal intelligence
      quotient. We used paternal obesity as negative control exposure as it involves
      the same source of confounding than maternal obesity.ResultsThe percentage of
      obese mothers and fathers was 8% and 12%, respectively. In unadjusted models,
      children of obese mothers had lower scores than children of normal weight mothers
      in all McCarthy subscales. After adjustment, only the verbal subscale remained
      statistically significantly reduced (beta: -2.8; 95% confidence interval: -5.3, 
      0.2). No associations were observed among obese fathers. Maternal and paternal
      obesity were associated with an increase in ADHD-related symptoms. Parental
      obesity was not associated with autism symptoms.ConclusionMaternal pre-pregnancy
      obesity was associated with a reduction in offspring verbal scores at pre-school
      age.

PMID- 28493862
TI  - FIMTrack: An open source tracking and locomotion analysis software for small
      animals.
AB  - Imaging and analyzing the locomotion behavior of small animals such as Drosophila
      larvae or C. elegans worms has become an integral subject of biological research.
      In the past we have introduced FIM, a novel imaging system feasible to extract
      high contrast images. This system in combination with the associated tracking
      software FIMTrack is already used by many groups all over the world. However, so
      far there has not been an in-depth discussion of the technical aspects. Here we
      elaborate on the implementation details of FIMTrack and give an in-depth
      explanation of the used algorithms. Among others, the software offers several
      tracking strategies to cover a wide range of different model organisms,
      locomotion types, and camera properties. Furthermore, the software facilitates
      stimuli-based analysis in combination with built-in manual tracking and
      correction functionalities. All features are integrated in an easy-to-use
      graphical user interface. To demonstrate the potential of FIMTrack we provide an
      evaluation of its accuracy using manually labeled data. The source code is
      available under the GNU GPLv3 at https://github.com/i-git/FIMTrack and pre
      compiled binaries for Windows and Mac are available at http://fim.uni
      muenster.de.

PMID- 28493863
TI  - Visceral leishmaniasis complicating idiopathic CD4+ T-cell lymphocytopenia: 2
      case reports.

PMID- 28493864
TI  - Power provides protection: Genetic robustness in yeast depends on the capacity to
      generate energy.
AB  - The functional basis of genetic robustness, the ability of organisms to suppress
      the effects of mutations, remains incompletely understood. We exposed a set of 15
      strains of Saccharomyces cerevisiae form diverse environments to increasing doses
      of the chemical mutagen EMS. The number of the resulting random mutations was
      similar for all tested strains. However, there were differences in immediate
      mortality after the mutagenic treatment and in defective growth of survivors. An
      analysis of gene expression revealed that immediate mortality was lowest in
      strains with lowest expression of transmembrane proteins, which are rich in thiol
      groups and thus vulnerable to EMS. A signal of genuine genetic robustness was
      detected for the other trait, the ability to grow well despite bearing non-lethal
      mutations. Increased tolerance of such mutations correlated with high expression
      of genes responsible for the oxidative energy metabolism, suggesting that the
      negative effect of mutations can be buffered if enough energy is available. We
      confirmed this finding in three additional tests of the ability to grow on (i)
      fermentable or non-fermentable sources of carbon, (ii) under chemical inhibition
      of the electron transport chain and (iii) during overexpression of its key
      component, cytochrome c. Our results add the capacity to generate energy as a
      general mechanism of genetic robustness.

PMID- 28493865
TI  - Preheating of urine improves the specificity of urinary cryptococcal antigen
      testing using the lateral flow assay.

PMID- 28493866
TI  - Initial assessment of the infant with neonatal cholestasis-Is this biliary
      atresia?
AB  - INTRODUCTION: Optimizing outcome in biliary atresia (BA) requires timely
      diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses
      (Non-BA). Identification of clinical features of neonatal cholestasis that would
      expedite decisions to pursue subsequent invasive testing to correctly diagnose or
      exclude BA would enhance outcomes. The analytical goal was to develop a
      predictive model for BA using data available at initial presentation. METHODS:
      Infants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2
      mg/dl [34.2 MUM]) were enrolled prior to surgical exploration in a prospective
      observational multi-centered study (PROBE-NCT00061828). Clinical features
      (physical findings, laboratory results, gallbladder sonography) at enrollment
      were analyzed. Initially, 19 features were selected as candidate predictors. Two
      approaches were used to build models for diagnosis prediction: a hierarchical
      classification and regression decision tree (CART) and a logistic regression
      model using a stepwise selection strategy. RESULTS: In PROBE April 2004-February
      2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis
      identified 13 features that were significantly different between BA and Non-BA.
      Using a CART predictive model of BA versus Non-BA (significant factors: gamma
      glutamyl transpeptidase, acholic stools, weight), the receiver operating
      characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA
      infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as
      BA. Stepwise logistic regression identified seven factors in a predictive model
      (ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357)
      yielded an 81% true positive rate for BA; <0.2 (n = 120) yielded an 11% false
      negative rate. CONCLUSION: Despite the relatively good accuracy of our optimized
      prediction models, the high precision required for differentiating BA from Non-BA
      was not achieved. Accurate identification of BA in infants with neonatal
      cholestasis requires further evaluation, and BA should not be excluded based only
      on presenting clinical features.

PMID- 28493867
TI  - Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction.
AB  - BACKGROUND: Induced pluripotent stem cells (iPSC) can be differentiated into
      cardiomyocytes and represent a possible autologous cell source for myocardial
      repair. We analyzed the engraftment and functional effects of murine iPSC-derived
      cardiomyocytes (iPSC-CMs) in a murine model of myocardial infarction. METHODS AND
      RESULTS: To maximize cardiomyocyte yield and purity a genetic purification
      protocol was applied. Murine iPSCs were genetically modified to express a
      ZeocinTM resistance gene under control of the cardiac-specific alpha-myosin heavy
      chain (alpha-MHC, MYH6) promoter. Thus, CM selection was performed during in
      vitro differentiation. iPSC-CM aggregates ("cardiac bodies", CBs) were
      transplanted on day 14 after LAD ligation into the hearts of previously LAD
      ligated mice (800 CBs/animal; 2-3x106 CMs). Animals were treated with placebo
      (PBS, n = 14) or iPSC-CMs (n = 35). Myocardial remodeling and function were
      evaluated by magnetic resonance imaging (MRI), conductance catheter (CC) analysis
      and histological morphometry. In vitro and in vivo differentiation was
      investigated. Follow up was 28 days (including histological assessment and
      functional analysis). iPSC-CM purity was >99%. Transplanted iPSC-CMs formed
      mature grafts within the myocardium, expressed cardiac markers and exhibited
      sarcomeric structures. Intramyocardial transplantation of iPSC-CMs significantly
      improved myocardial remodeling and left ventricular function 28 days after LAD
      ligation. CONCLUSIONS: We conclude that iPSCs can effectively be differentiated
      into cardiomyocytes and genetically enriched to high purity. iPSC derived
      cardiomyocytes engraft within the myocardium of LAD-ligated mice and contribute
      to improve left ventricular function.

PMID- 28493868
TI  - Vertical ground reaction force marker for Parkinson's disease.
AB  - Parkinson's disease (PD) patients regularly exhibit abnormal gait patterns.
      Automated differentiation of abnormal gait from normal gait can serve as a
      potential tool for early diagnosis as well as monitoring the effect of PD
      treatment. The aim of current study is to differentiate PD patients from healthy
      controls, on the basis of features derived from plantar vertical ground reaction
      force (VGRF) data during walking at normal pace. The current work presents a
      comprehensive study highlighting the efficacy of different machine learning
      classifiers towards devising an accurate prediction system. Selection of
      meaningful feature based on sequential forward feature selection, the swing time,
      stride time variability, and center of pressure features facilitated successful
      classification of control and PD gaits. Support Vector Machine (SVM), K-nearest
      neighbor (KNN), random forest, and decision trees classifiers were used to build
      the prediction model. We found that SVM with cubic kernel outperformed other
      classifiers with an accuracy of 93.6%, the sensitivity of 93.1%, and specificity
      of 94.1%. In comparison to other studies, utilizing same dataset, our designed
      prediction system improved the classification performance by approximately 10%.
      The results of the current study underscore the ability of the VGRF data obtained
      non-invasively from wearable devices, in combination with a SVM classifier
      trained on meticulously selected features, as a tool for diagnosis of PD and
      monitoring effectiveness of therapy post pathology.

PMID- 28493869
TI  - Identification of the potentiating mutations and synergistic epistasis that
      enabled the evolution of inter-species cooperation.
AB  - Microbes often engage in cooperation through releasing biosynthetic compounds
      required by other species to grow. Given that production of costly biosynthetic
      metabolites is generally subjected to multiple layers of negative feedback,
      single mutations may frequently be insufficient to generate cooperative
      phenotypes. Synergistic epistatic interactions between multiple coordinated
      changes may thus often underlie the evolution of cooperation through
      overproduction of metabolites. To test the importance of synergistic mutations in
      cooperation we used an engineered bacterial consortium of an Escherichia coli
      methionine auxotroph and Salmonella enterica. S. enterica relies on carbon by
      products from E. coli if lactose is the only carbon source. Directly selecting
      wild-type S. enterica in an environment that favored cooperation through
      secretion of methionine only once led to a methionine producer, and this producer
      both took a long time to emerge and was not very effective at cooperating. On the
      other hand, when an initial selection for resistance of S. enterica to a toxic
      methionine analog, ethionine, was used, subsequent selection for cooperation with
      E. coli was rapid, and the resulting double mutants were much more effective at
      cooperation. We found that potentiating mutations in metJ increase expression of
      metA, which encodes the first step of methionine biosynthesis. This increase in
      expression is required for the previously identified actualizing mutations in
      metA to generate cooperation. This work highlights that where biosynthesis of
      metabolites involves multiple layers of regulation, significant secretion of
      those metabolites may require multiple mutations, thereby constraining the
      evolution of cooperation.

PMID- 28493871
TI  - Ileus in children presenting with diarrhea and severe acute malnutrition: A chart
      review.
AB  - BACKGROUND: Severely malnourished children aged under five years requiring
      hospital admission for diarrheal illness frequently develop ileus during
      hospitalization with often fatal outcomes. However, there is no data on risk
      factors and outcome of ileus in such children. We intended to evaluate predictive
      factors for ileus during hospitalization and their outcomes.
      METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective chart review that
      enrolled severely malnourished children under five years old with diarrhea,
      admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease
      Research, Bangladesh between April 2011 and August 2012. We used electronic
      database to have our chart abstraction from previously admitted children in the
      hospital. The clinical and laboratory characteristics of children with (cases =
      45), and without ileus (controls = 261) were compared. Cases were first
      identified by observation of abnormal bowel sounds on physical examination and
      confirmed with abdominal radiographs. For this comparison, Chi-square test was
      used to measure the difference in proportion, Student's t-test to calculate the
      difference in mean for normally distributed data and Mann-Whitney test for data
      that were not normally distributed. Finally, in identifying independent risk
      factors for ileus, logistical regression analysis was performed. Ileus was
      defined if a child developed abdominal distension and had hyperactive or sluggish
      or absent bowel sound and a radiologic evidence of abdominal gas-fluid level
      during hospitalization. Logistic regression analysis adjusting for potential
      confounders revealed that the independent risk factors for admission for ileus
      were reluctance to feed (odds ratio [OR] = 3.22, 95% confidence interval [CI] =
      1.24-8.39, p = 0.02), septic shock (OR = 3.62, 95% CI = 1.247-8.95, p<0.01), and
      hypokalemia (OR = 1.99, 95% CI = 1.03-3.86, p = 0.04). Mortality was
      significantly higher in cases compared to controls (22% vs. 8%, p<0.01) in
      univariate analysis; however, in multivariable regression analysis, after
      adjusting for potential confounders such as septic shock, no association was
      found between ileus and death (OR = 2.05, 95% CI = 0.68-6.14, p = 0.20). In a
      separate regression analysis model, after adjusting for potential confounders
      such as ileus, reluctance to feed, hypokalemia, hypocalcemia, and blood
      transfusion, septic shock (OR = 168.84, 95% CI = 19.27-1479.17, p<0.01) emerged
      as the only independent predictor of death in severely malnourished diarrheal
      children. CONCLUSIONS/SIGNIFICANCE: This study suggests that the identification
      of simple independent admission risk factors for ileus and risk factors for death
      in hospitalized severely malnourished diarrheal children may prompt clinicians to
      be more vigilant in managing these conditions, especially in resource-limited
      settings in order to decrease ileus and ileus-related fatal outcomes in such
      children.

PMID- 28493872
TI  - Geographic distribution of vestibular schwannomas in West Scotland between 2000
      2015.
AB  - BACKGROUND: Although the natural history of vestibular schwannomas (VS) has been
      previously studied, few studies have investigated associated epidemiological
      factors, primarily because of the lack of large available cohorts. OBJECTIVE: The
      objective of this study was to perform a multi-scale geographical analysis of the
      period prevalence of VS in West Scotland from 2000 to 2015. METHODS: Adults
      diagnosed with sporadic VS were identified through the National Health Services
      of West Scotland database and geocoded to the unit postcode. To assess whether
      the cohort of VS cases could be pooled into a period prevalence measure, the
      locations of VS cases were analyzed by sex using Cross-L and Difference-K
      functions. VS period prevalence was examined at two aggregate spatial scales: the
      postcode district and a coarser scale of NHS Health Boards. The spatial structure
      of period prevalence within each level of spatial aggregation was measured using
      univariate global and local Moran's I. Bivariate local Moran's I was used to
      examine the between-scale variability in period prevalence from the postcode
      district level to the NHS Health Boards levels. Prior to spatial autocorrelation
      analyses, the period prevalence at the postcode district was tested for
      stratified spatial heterogeneity within the NHS Health Boards using Wang's q
      Statistic. RESULTS: A total of 512 sporadic VS were identified in a population of
      over 3.1 million. Between 2000 and 2015, VS period prevalence was highest within
      the NHS Health Boards of Greater Glasgow and Clyde, Ayrshire and Arran and the
      Western Isles. However, at the NHS scale, period prevalence exhibited no spatial
      autocorrelation globally or locally. At the district scale, Highland exhibited
      the most unusual local spatial autocorrelation. Bivariate local Moran's I results
      indicated general stability of period prevalence across the postcode district to
      Health Boards scales. However, locally, some postcode districts in Greater
      Glasgow and Clyde, Ayrshire and Arran exhibited unusually low district to zone
      spatial autocorrelation in period prevalence, as did the southern parts of the
      Western Isles. Some unusually high period prevalence values between the postcode
      district to Health Board scale were found in Tayside, Forth Valley and Dumfries
      and Galloway. CONCLUSION: Geographic variability in VS in West Scotland was
      identified in this patient population, showing that there are areas, even remote,
      with unusually high or low period prevalence. This can be partially attributed to
      links between primary and tertiary care. Potential genetic or environmental risk
      factors that may contribute to geographic variation in this disease within
      Scotland are also a possibility but require further investigation.

PMID- 28493870
TI  - Functional male accessory glands and fertility in Drosophila require novel
      ecdysone receptor.
AB  - In many insects, the accessory gland, a secretory tissue of the male reproductive
      system, is essential for male fertility. Male accessory gland is the major source
      of proteinaceous secretions, collectively called as seminal proteins (or
      accessory gland proteins), which upon transfer, manipulate the physiology and
      behavior of mated females. Insect hormones such as ecdysteroids and juvenoids
      play a key role in accessory gland development and protein synthesis but little
      is known about underlying molecular players and their mechanism of action.
      Therefore, in the present study, we examined the roles of hormone-dependent
      transcription factors (Nuclear Receptors), in accessory gland development,
      function and male fertility of a genetically tractable insect model, Drosophila
      melanogaster. First, we carried out an RNAi screen involving 19 hormone
      receptors, individually and specifically, in a male reproductive tissue
      (accessory gland) for their requirement in Drosophila male fertility.
      Subsequently, by using independent RNAi/ dominant negative forms, we show that
      Ecdysone Receptor (EcR) is essential for male fertility due to its requirement in
      the normal development of accessory glands in Drosophila: EcR depleted glands
      fail to make seminal proteins and have dying cells. Further, our data point to a
      novel ecdysone receptor that does not include Ultraspiracle but is probably
      comprised of EcR isoforms in Drosophila male accessory glands. Our data suggest
      that this novel ecdysone receptor might act downstream of homeodomain
      transcription factor paired (prd) in the male accessory gland. Overall, the study
      suggests novel ecdysone receptor as an important player in the hormonal
      regulation of seminal protein production and insect male fertility.

PMID- 28493873
TI  - Modeling of a negative feedback mechanism explains antagonistic pleiotropy in
      reproduction in domesticated Caenorhabditis elegans strains.
AB  - Most biological traits and common diseases have a strong but complex genetic
      basis, controlled by large numbers of genetic variants with small contributions
      to a trait or disease risk. The effect-size of most genetic variants is not
      absolute and is instead dependent upon multiple factors such as the age and
      genetic background of an organism. In order to understand the mechanistic basis
      of these changes, we characterized heritable trait differences between two
      domesticated strains of C. elegans. We previously identified a major effect
      locus, caused in part by a mutation in a component of the NURF chromatin
      remodeling complex, that regulates reproductive output in an age-dependent
      manner. The effect-size of this locus changes from positive to negative over the
      course of an animal's reproductive lifespan. Here, we use a previously published
      macroscale model of the egg-laying rate in C. elegans to show that time-dependent
      effect-size is explained by an unequal use of sperm combined with negative
      feedback between sperm and ovulation rate. We validate key predictions of this
      model with controlled mating experiments and quantification of oogenesis and
      sperm use. Incorporation of this model into QTL mapping allows us to identify and
      partition new QTLs into specific aspects of the egg-laying process. Finally, we
      show how epistasis between two genetic variants is predicted by this modeling as
      a consequence of the unequal use of sperm. This work demonstrates how modeling of
      multicellular communication systems can improve our ability to predict and
      understand the role of genetic variation on a complex phenotype. Negative
      autoregulatory feedback loops, common in transcriptional regulation, could play
      an important role in modifying genetic architecture in other traits.

PMID- 28493874
TI  - SrCrxFe12-xO19 nanoceramics as an effective catalyst for desulfurization of
      liquid fuels: Green sol-gel synthesis, characterization, magnetic and optical
      properties.
AB  - In this work, SrCrxFe12-xO19 (x = 0.0, 0.5, 1.0, 1.5) nanostructures were
      successfully synthesized by sol-gel auto-combustion method, and different
      aminoacids were used as green reductants. Various analysis results show that
      SrCrxFe12-xO19 nanoparticles synthesized successfully.The present study shows
      that SrCrxFe12-xO19 nanoparticle could be used as adsorbent for the
      desulfurization of liquid fuels. Increasing of nanoparticles concentration was
      caused to increase the adsorption rate of sulfur contents of fuel. The adsorption
      rate of sulfur contents of fuel in various concentrations 4.5, 9.5, and 18.5 g. L
      -1 of SrCrxFe12-xO19 nanoparticles in solution was estimated about 39, 50, and
      62% for 30 min, respectively. The results of catalytic tests reveals that
      SrCrxFe12-xO19 nanoparticles have the potential to be used as a new kind of
      semiconductor catalysts for the desulfurization of liquid fuels. Magnetic
      property of the final sample was measured at room temperature by a vibration
      sample magnetometer (VSM) and shown that the intrinsic coercivity of product is
      about 6000 Oe and it exhibits characteristics of single magnetic domains (Mr/ Ms
      = 0.53).

PMID- 28493875
TI  - Effect of a high-fat diet and alcohol on cutaneous repair: A systematic review of
      murine experimental models.
AB  - BACKGROUND AND PURPOSE: Chronic alcohol intake associated with an inappropriate
      diet can cause lesions in multiple organs and tissues and complicate the tissue
      repair process. In a systematic review, we analyzed the relevance of alcohol and
      high fat consumption to cutaneous and repair, compared the main methodologies
      used and the most important parameters tested. Preclinical investigations with
      murine models were assessed to analyze whether the current evidence support
      clinical trials. METHODS: The studies were selected from MEDLINE/PubMed and
      Scopus databases, according to Fig 1. All 15 identified articles had their data
      extracted. The reporting bias was investigated according to the ARRIVE (Animal
      Research: Reporting of in Vivo Experiments) strategy. RESULTS: In general,
      animals offered a high-fat diet and alcohol showed decreased cutaneous wound
      closure, delayed skin contraction, chronic inflammation and incomplete re
      epithelialization. CONCLUSION: In further studies, standardized experimental
      design is needed to establish comparable study groups and advance the overall
      knowledge background, facilitating data translatability from animal models to
      human clinical conditions.

PMID- 28493876
TI  - The effect of sphingosine-1-phosphate on colonic smooth muscle contractility:
      Modulation by TNBS-induced colitis.
AB  - AIM: Increased levels of circulating sphingosine-1-phosphate (S1P) have been
      reported in ulcerative colitis. The objective of this study was to examine the
      effect of S1P on colonic smooth muscle contractility and how is it affected by
      colitis. METHODS: Colonic inflammation was induced by intrarectal administration
      of trinitrobenzene sulfonic acid. Five days later colon segments were isolated
      and used for contractility experiments and immunoblotting. RESULTS: S1P
      contracted control and inflamed colon segments and the contraction was
      significantly greater in inflamed colon segments. S1P-induced contraction was
      mediated by S1PR1 and S1PR2 in control and S1PR2 in inflamed colon segments.
      S1PR3 did not play a significant role in S1P-induced contractions in control or
      inflamed colon. S1PR1, S1PR2 and S1PR3 proteins were expressed in colon segments
      from both groups. The expression of S1PR1 and S1PR2 was significantly enhanced in
      control and inflamed colon segments, respectively. S1PR3 levels however were not
      significantly different between the two groups. Nifedipine significantly reduced
      S1P-induced contraction in control but not inflamed colon segments. Thapsigargin
      significantly reduced S1P-induced contraction of the inflamed colon. GF 109203X
      and Y-27632, alone abolished S1P-induced contraction of the control but not
      inflamed colon segments. Combination of GF 109203X, Y-27632 and thapsigargin
      abolished S1P-induced contraction of inflamed colon segments. CONCLUSION: S1P
      contracted control colon via S1PR1 and S1PR2 and inflamed colon exclusively via
      S1PR2. Calcium influx (control) or release (inflamed) and calcium sensitization
      are involved in S1P-induced contraction. Exacerbated response to S1P in colitic
      colon segments may explain altered colonic motility reported in patients and
      experimental models of inflammatory bowel disease.

PMID- 28493877
TI  - CO2 driven endotracheal tube cuff control in critically ill patients: A
      randomized controlled study.
AB  - BACKGROUND: To determine the safety and clinical efficacy of an innovative
      integrated airway system (AnapnoGuardTM 100 system) that continuously monitors
      and controls the cuff pressure (Pcuff), while facilitating the aspiration of
      subglottic secretions (SS). METHODS: This was a prospective, single centre, open
      label, randomized, controlled feasibility and safety trial. The primary endpoint
      of the study was the rate of device related adverse events (AE) and serious AE
      (SAE) as a result of using AnapnoGuard (AG) 100 during mechanical ventilation.
      Secondary endpoints were: (1) mechanical complications rate (2) ICU staff
      satisfaction; (3) VAP occurrence; (4) length of mechanical ventilation; (5)
      length of Intensive Care Unit stay and mortality; (6) volume of evacuated
      subglottic secretions. Sixty patients were randomized to be intubated with the AG
      endotracheal-tube (ETT) and connected to the AG 100 system allowing Pcuff
      adjustment and SS aspiration; or with an ETT combined with SS drainage and Pcuff
      controlled manually. RESULTS: No difference in adverse events rate was identified
      between the groups. The use of AG system was associated with a significantly
      higher incidence of Pcuff determinations in the safety range (97.3% vs. 71%;
      p<0.01) and a trend to a greater volume of aspirated SS secretions: (192.0[64
      413] ml vs. 150[50-200], p = 0.19 (total)); (57.8[20-88.7] ml vs. 50[18.7-62] ml,
      p = 0.11 (daily)). No inter-group difference was detected using AG system vs.
      controls in terms of post-extubation throat pain level (0 [0-2] vs. 0 [0-3]; p =
      0.7), hoarseness (42.9% vs. 75%; p = 0.55) and tracheal mucosa oedema (16.7% vs.
      10%; p = 0.65). Patients enrolled in the AG group had a trend to reduced VAP risk
      of ventilator-associated pneumonia(VAP) (14.8% vs. 40%; p = 0.06), which were
      more frequently monomicrobial (25% vs. 70%; p = 0.03). No statistically
      significant difference was observed in duration of mechanical ventilation, ICU
      stay, and mortality. CONCLUSIONS: The use AG 100 system and AG tube in critically
      ill intubated patients is safe and effective in Pcuff control and SS drainage.
      Its protective role against VAP needs to be confirmed in a larger randomized
      trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01550978. Date of registration:
      February 21, 2012.

PMID- 28493878
TI  - 5alpha-reductase 1 mRNA levels are positively correlated with TRAMP mouse
      prostate most severe lesion scores.
AB  - BACKGROUND: The contribution of 5alpha-reductase 1 and 5alpha-reductase 2 to
      prostate cancer development and progression is not clearly understood. TRAMP mice
      are a common prostate cancer model, in which 5alpha-reductase 1 and 5alpha
      reductase 2 expression levels, along with prostate lesions scores, have not been
      investigated at different time points to further understand prostate
      carcinogenesis. METHOD/PRINCIPAL FINDINGS: To this end, 8-, 12-, 16-, and 20-week
      old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion
      scores, 5alpha-reductase 1 and 5alpha-reductase 2 in situ hybridization
      expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry
      levels were measured. Levels of these markers were quantified in prostate
      epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade
      prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common
      lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12
      and 16 weeks as the most severe lesion in all lobes. Moderately differentiated
      adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated
      carcinoma was not observed in any lobe until 12-weeks-old. 5alpha-reductase 1 and
      5alpha-reductase 2 were not significantly decreased in tumors compared to
      prostate epithelium and hyperplasia in all groups, while proliferation,
      apoptosis, and androgen receptor were either notably or significantly decreased
      in tumors compared with prostate epithelium and hyperplasia in most or all
      groups. Prostate 5alphaR1 levels were positively correlated with adjusted
      prostate most severe lesion scores. CONCLUSION: Downregulation of androgen
      receptor and 5alpha-reductase 2, along with upregulation of 5alpha-reductase 1 in
      tumors may promote prostatic intraepithelial neoplasia and prostate cancer
      development in TRAMP mice.

PMID- 28493879
TI  - Heterogeneous Ag-TiO2-SiO2 composite materials as novel catalytic systems for
      selective epoxidation of cyclohexene by H2O2.
AB  - TiO2-SiO2 composites were synthesized using cetyl trimethyl ammonium bromide
      (CTAB) as the structure directing template. Self-assembly hexadecyltrimethyl-
      ammonium bromide TiO2-SiO2/(CTAB) were soaked into silver nitrate (AgNO3) aqueous
      solution. The Ag-TiO2-SiO2(Ag-TS) composite were prepared via a precipitation of
      AgBr in soaking process and its decomposition at calcination stage. Structural
      characterization of the materials was carried out by various techniques including
      X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), N2 adsorption-desorption and ultraviolet visible
      spectroscopy (UV-Vis). Characterization results revealed that Ag particles were
      incorporated into hierarchical TiO2-SiO2 without significantly affecting the
      structures of the supports. Further heating-treatment at 723 K was more favorable
      for enhancing the stability of the Ag-TS composite. The cyclohexene oxide was the
      major product in the epoxidation using H2O2 as the oxidant over the Ag-TS
      catalysts. Besides, the optimum catalytic activity and stability of Ag-TS
      catalysts were obtained under operational conditions of calcined at 723 K for 2
      h, reaction time of 120 min, reaction temperature of 353 K, catalyst amount of 80
      mg, aqueous H2O2 (30 wt.%) as oxidant and chloroform as solvent. High catalytic
      activity with conversion rate up to 99.2% of cyclohexene oxide could be
      obtainable in water-bathing. The catalyst was found to be stable and could be
      reused three times without significant loss of catalytic activity under the
      optimized reaction conditions.

PMID- 28493880
TI  - Identifying stochastic oscillations in single-cell live imaging time series using
      Gaussian processes.
AB  - Multiple biological processes are driven by oscillatory gene expression at
      different time scales. Pulsatile dynamics are thought to be widespread, and
      single-cell live imaging of gene expression has lead to a surge of dynamic,
      possibly oscillatory, data for different gene networks. However, the regulation
      of gene expression at the level of an individual cell involves reactions between
      finite numbers of molecules, and this can result in inherent randomness in
      expression dynamics, which blurs the boundaries between aperiodic fluctuations
      and noisy oscillators. This underlies a new challenge to the experimentalist
      because neither intuition nor pre-existing methods work well for identifying
      oscillatory activity in noisy biological time series. Thus, there is an acute
      need for an objective statistical method for classifying whether an
      experimentally derived noisy time series is periodic. Here, we present a new data
      analysis method that combines mechanistic stochastic modelling with the powerful
      methods of non-parametric regression with Gaussian processes. Our method can
      distinguish oscillatory gene expression from random fluctuations of non
      oscillatory expression in single-cell time series, despite peak-to-peak
      variability in period and amplitude of single-cell oscillations. We show that our
      method outperforms the Lomb-Scargle periodogram in successfully classifying cells
      as oscillatory or non-oscillatory in data simulated from a simple genetic
      oscillator model and in experimental data. Analysis of bioluminescent live-cell
      imaging shows a significantly greater number of oscillatory cells when luciferase
      is driven by a Hes1 promoter (10/19), which has previously been reported to
      oscillate, than the constitutive MoMuLV 5' LTR (MMLV) promoter (0/25). The method
      can be applied to data from any gene network to both quantify the proportion of
      oscillating cells within a population and to measure the period and quality of
      oscillations. It is publicly available as a MATLAB package.

PMID- 28493881
TI  - shinyheatmap: Ultra fast low memory heatmap web interface for big data genomics.
AB  - BACKGROUND: Transcriptomics, metabolomics, metagenomics, and other various next
      generation sequencing (-omics) fields are known for their production of large
      datasets, especially across single-cell sequencing studies. Visualizing such big
      data has posed technical challenges in biology, both in terms of available
      computational resources as well as programming acumen. Since heatmaps are used to
      depict high-dimensional numerical data as a colored grid of cells, efficiency and
      speed have often proven to be critical considerations in the process of
      successfully converting data into graphics. For example, rendering interactive
      heatmaps from large input datasets (e.g., 100k+ rows) has been computationally
      infeasible on both desktop computers and web browsers. In addition to memory
      requirements, programming skills and knowledge have frequently been barriers-to
      entry for creating highly customizable heatmaps. RESULTS: We propose
      shinyheatmap: an advanced user-friendly heatmap software suite capable of
      efficiently creating highly customizable static and interactive biological
      heatmaps in a web browser. shinyheatmap is a low memory footprint program, making
      it particularly well-suited for the interactive visualization of extremely large
      datasets that cannot typically be computed in-memory due to size restrictions.
      Also, shinyheatmap features a built-in high performance web plug-in, fastheatmap,
      for rapidly plotting interactive heatmaps of datasets as large as 105-107 rows
      within seconds, effectively shattering previous performance benchmarks of heatmap
      rendering speed. CONCLUSIONS: shinyheatmap is hosted online as a freely available
      web server with an intuitive graphical user interface: http://shinyheatmap.com.
      The methods are implemented in R, and are available as part of the shinyheatmap
      project at: https://github.com/Bohdan-Khomtchouk/shinyheatmap. Users can access
      fastheatmap directly from within the shinyheatmap web interface, and all source
      code has been made publicly available on Github: https://github.com/Bohdan
      Khomtchouk/fastheatmap.

PMID- 28493882
TI  - Selective pre-priming of HA-specific CD4 T cells restores immunological
      reactivity to HA on heterosubtypic influenza infection.
AB  - A hallmark of the immune response to influenza is repeated encounters with
      proteins containing both genetically conserved and variable components.
      Therefore, the B and T cell repertoire is continually being remodeled, with
      competition between memory and naive lymphocytes. Our previous work using a mouse
      model of secondary heterosubtypic influenza infection has shown that this
      competition results in a focusing of CD4 T cell response specificity towards
      internal virion proteins with a selective decrease in CD4 T cell reactivity to
      the novel HA epitopes. Strikingly, this shift in CD4 T cell specificity was
      associated with a diminished anti-HA antibody response. Here, we sought to
      determine whether the loss in HA-specific reactivity that occurs as a consequence
      of immunological memory could be reversed by selectively priming HA-specific CD4
      T cells prior to secondary infection. Using a peptide-based priming strategy, we
      found that selective expansion of the anti-HA CD4 T cell memory repertoire
      enhanced HA-specific antibody production upon heterosubtypic infection. These
      results suggest that the potentially deleterious consequences of repeated
      exposure to conserved influenza internal virion proteins could be reversed by
      vaccination strategies that selectively arm the HA-specific CD4 T cell
      compartment. This could be a potentially useful pre-pandemic vaccination strategy
      to promote accelerated neutralizing antibody production on challenge with a
      pandemic influenza strain that contains few conserved HA epitopes.

PMID- 28493883
TI  - Lithocholic acid controls adaptive immune responses by inhibition of Th1
      activation through the Vitamin D receptor.
AB  - Bile acids are established signaling molecules next to their role in the
      intestinal emulsification and uptake of lipids. We here aimed to identify a
      potential interaction between bile acids and CD4+ Th cells, which are central in
      adaptive immune responses. We screened distinct bile acid species for their
      potency to affect T cell function. Primary human and mouse CD4+ Th cells as well
      as Jurkat T cells were used to gain insight into the mechanism underlying these
      effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation
      as measured by i) decreased production of the Th1 cytokines IFNgamma and
      TNFalphaalpha, ii) decreased expression of the Th1 genes T-box protein expressed
      in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1alpha/beta
      phosphorylation. Importantly, we observed that LCA impairs Th1 activation at
      physiological relevant concentrations. Profiling of MAPK signaling pathways in
      Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA
      exposure, which could provide an explanation for the impaired Th1 activation. LCA
      induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA
      silencing abrogated these effects. These data reveal for the first time that LCA
      controls adaptive immunity via inhibition of Th1 activation. Many factors
      influence LCA levels, including bile acid-based drugs and gut microbiota. Our
      data may suggest that these factors also impact on adaptive immunity via a yet
      unrecognized LCA-Th cell axis.

PMID- 28493884
TI  - Non-linear growth in tree ferns, Dicksonia antarctica and Cyathea australis.
AB  - Tree ferns are an important structural component of forests in many countries.
      However, because their regeneration is often unrelated to major disturbances,
      their age is often difficult to determine. In addition, rates of growth may not
      be uniform, which further complicates attempts to determine their age. In this
      study, we measured 5 years of growth of Cyathea australis and Dicksonia
      antarctica after a large wildfire in 2009 in south-eastern Australia. We found
      growth rates of these two species were unaffected by aspect and elevation but
      slope had a minor effect with D. antarctica growing 0.3mm faster for each
      additional degree of slope. Geographic location influenced growth in both species
      by up to 12 - 14mm/yr. The most consistent factor influencing growth rate,
      however, was initial height at the time of the 2009 fire; a finding consistent in
      both species and all geographic locations. For both tree fern species,
      individuals that were taller at the commencement of the study had greater overall
      growth for the duration of the study. This effect did not decrease even among the
      tallest tree ferns in our study (up to 6 metres tall). Overall, Cyathea australis
      averaged 73 (+/- 22)mm/year of growth (+/- 1SD), with the rate increasing 5mm/yr
      per metre of additional height. Dicksonia antarctica averaged 33 (+/- 13)mm/year,
      increasing by 6mm/yr/m. Growth rates dependent on initial height were unexpected
      and we discuss possible reasons for this finding. Variable growth rates also
      suggest that common age estimation methods of dividing height by average growth
      rate are likely to underestimate the age of short tree ferns, while
      overestimating the age of tall tree ferns, particularly if they have been subject
      to a fire.

PMID- 28493886
TI  - Narrow microtunnel technology for the isolation and precise identification of
      axonal communication among distinct hippocampal subregion networks.
AB  - Communication between different sub regions of the hippocampus is fundamental to
      learning and memory. However accurate knowledge about information transfer
      between sub regions from access to the activity in individual axons is lacking.
      MEMS devices with microtunnels connecting two sub networks have begun to approach
      this problem but the commonly used 10 MUm wide tunnels frequently measure signals
      from multiple axons. To reduce this complexity, we compared polydimethylsiloxane
      (PDMS) microtunnel devices each with a separate tunnel width of 2.5, 5 or 10 MUm
      bridging two wells aligned over a multi electrode array (MEA). Primary rat
      neurons were grown in the chambers with neurons from the dentate gyrus on one
      side and hippocampal CA3 on the other. After 2-3 weeks of culture, spontaneous
      activity in the axons inside the tunnels was recorded. We report
      electrophysiological, exploratory data analysis for feature clustering and visual
      evidence to support the expectation that 2.5 MUm wide tunnels have fewer axons
      per tunnel and therefore more clearly delineated signals than 10 or 5 MUm wide
      tunnels. Several measures indicated that fewer axons per electrode enabled more
      accurate detection of spikes. A clustering analysis comparing the variations of
      spike height and width for different tunnel widths revealed tighter clusters
      representing unique spikes with less height and width variation when measured in
      narrow tunnels. Wider tunnels tended toward more diffuse clusters from a
      continuum of spike heights and widths. Standard deviations for multiple cluster
      measures, such as Average Dissimilarity, Silhouette Value (S) and Separation
      Factor (average dissimilarity/S value), support a conclusion that 2.5 MUm wide
      tunnels containing fewer axons enable more precise determination of individual
      action potential peaks, their propagation direction, timing, and information
      transfer between sub networks.

PMID- 28493885
TI  - Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates,
      their comparison with strain GG and their recognition by complement system.
AB  - Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the
      human body where they are commensals naturally present in the normal microbiota
      composition of gut, vagina and skin. However, in some cases, Lactobacillus spp.
      have been implicated in bacteremia. The aim of the study was to examine the
      genomic and immunological properties of 16 clinical blood isolates of L.
      rhamnosus and to compare them to the well-studied L. rhamnosus probiotic strain
      GG. Blood cultures from bacteremic patients were collected at the Helsinki
      University Hospital laboratory in 2005-2011 and L. rhamnosus strains were
      isolated and characterized by genomic sequencing. The capacity of the L.
      rhamnosus strains to activate serum complement was studied using immunological
      assays for complement factor C3a and the terminal pathway complement complex
      (TCC). Binding of complement regulators factor H and C4bp was also determined
      using radioligand assays. Furthermore, the isolated strains were evaluated for
      their ability to aggregate platelets and to form biofilms in vitro. Genomic
      comparison between the clinical L. rhamnosus strains showed them to be clearly
      different from L. rhamnosus GG and to cluster in two distinct lineages. All L.
      rhamnosus strains activated complement in serum and none of them bound complement
      regulators. Four out of 16 clinical blood isolates induced platelet aggregation
      and/or formed more biofilms than L. rhamnosus GG, which did not display platelet
      aggregation activity nor showed strong biofilm formation. These findings suggest
      that clinical L. rhamnosus isolates show considerable heterogeneity but are
      clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus
      strains are still normally recognized by the human complement system.

PMID- 28493887
TI  - Effect of lifestyle interventions on cardiovascular risk factors among adults
      without impaired glucose tolerance or diabetes: A systematic review and meta
      analysis.
AB  - Structured lifestyle interventions can reduce diabetes incidence and
      cardiovascular disease (CVD) risk among persons with impaired glucose tolerance
      (IGT), but it is unclear whether they should be implemented among persons without
      IGT. We conducted a systematic review and meta-analyses to assess the
      effectiveness of lifestyle interventions on CVD risk among adults without IGT or
      diabetes. We systematically searched MEDLINE, EMBASE, CINAHL, Web of Science, the
      Cochrane Library, and PsychInfo databases, from inception to May 4, 2016. We
      selected randomized controlled trials of lifestyle interventions, involving
      physical activity (PA), dietary (D), or combined strategies (PA+D) with follow-up
      duration >=12 months. We excluded all studies that included individuals with IGT,
      confirmed by 2-hours oral glucose tolerance test (75g), but included all other
      studies recruiting populations with different glycemic levels. We stratified
      studies by baseline glycemic levels: (1) low-range group with mean fasting plasma
      glucose (FPG) <5.5mmol/L or glycated hemoglobin (A1C) <5.5%, and (2) high-range
      group with FPG >=5.5mmol/L or A1C >=5.5%, and synthesized data using random
      effects models. Primary outcomes in this review included systolic blood pressure
      (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density
      lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C),
      and triglycerides (TG). Totally 79 studies met inclusion criteria. Compared to
      usual care (UC), lifestyle interventions achieved significant improvements in SBP
      (-2.16mmHg[95%CI, -2.93, -1.39]), DBP (-1.83mmHg[-2.34, -1.31]), TC (-0.10mmol/L[
      0.15, -0.05]), LDL-C (-0.09mmol/L[-0.13, -0.04]), HDL-C (0.03mmol/L[0.01, 0.04]),
      and TG (-0.08mmol/L[-0.14, -0.03]). Similar effects were observed among both low
      and high-range study groups except for TC and TG. Similar effects also appeared
      in SBP and DBP categories regardless of follow-up duration. PA+D interventions
      had larger improvement effects on CVD risk factors than PA alone interventions.
      In adults without IGT or diabetes, lifestyle interventions resulted in
      significant improvements in SBP, DBP, TC, LDL-C, HDL-C, and TG, and might further
      reduce CVD risk.

PMID- 28493889
TI  - Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin
      (NCX-4040) on Candida albicans isolates from denture stomatitis patients.
AB  - Candida albicans biofilms play a key role in denture stomatitis, one of the most
      common oral pathologies in elderly people. Because biofilms are highly resistant
      to antifungals, new pharmacological strategies are needed. Aspirin and nitric
      oxide-donor molecules have both shown antibiofilm effects on C. albicans, making
      them promising candidates for treatment. In this study, we evaluated the
      antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C.
      albicans isolates from denture stomatitis patients in vitro. Disk diffusion
      assays showed that while NO-ASA had no antifungal effect, the drug potentiated
      fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20
      30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was
      evaluated using light microscopy after inducing hyphae formation. For all
      clinical strains assayed, 125 MUM NO-ASA significantly decreased the number of
      filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical
      event for biofilm formation, was evaluated in 96-well polystyrene plates using
      crystal violet assay; 125 MUM NO-ASA significantly inhibited adhesion. Biofilms
      were observed with scanning electron microscopy (SEM) and quantified using XTT
      reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 MUM to
      700 MUM), consistent with SEM findings of altered biofilm microarchitecture. PGE2
      and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO
      ASA, suggesting that the efficacy of NO-ASA may be associated with both
      inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel
      antibiofilm agent for treating fluconazole-resistant strains of C. albicans.

PMID- 28493888
TI  - The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani
      growth and infectivity.
AB  - BACKGROUND: Leishmania donovani, a protozoan parasite is the major causative
      agent of visceral leishmaniasis. Increased toxicity and resistance to the
      existing repertoire of drugs has been reported. Hence, an urgent need exists for
      identifying newer drugs and drug targets. Previous reports have shown sirtuins
      (Silent Information Regulator) from kinetoplastids as promising drug targets.
      Leishmania species code for three SIR2 (Silent Information Regulator) related
      proteins. Here, we for the first time report the functional characterization of
      SIR2 related protein 2 (SIR2RP2) of L. donovani. METHODOLOGY: Recombinant L.
      donovani SIR2RP2 was expressed in E. coli and purified. The enzymatic functions
      of SIR2RP2 were determined. The subcellular localization of LdSIR2RP2 was done by
      constructing C-terminal GFP-tagged full-length LdSIR2RP2. Deletion mutants of
      LdSIR2RP2 were generated in Leishmania by double targeted gene replacement
      methodology. These null mutants were tested for their proliferation, virulence,
      cell cycle defects, mitochondrial functioning and sensitivity to known SIR2
      inhibitors. CONCLUSION: Our data suggests that LdSIR2RP2 possesses NAD+-dependent
      ADP-ribosyltransferase activity. However, NAD+-dependent deacetylase and
      desuccinylase activities were not detected. The protein localises to the
      mitochondrion of the promastigotes. Gene deletion studies showed that
      DeltaLdSIR2RP2 null mutants had restrictive growth phenotype associated with
      accumulation of cells in the G2/M phase and compromised mitochondrial
      functioning. The null mutants had attenuated infectivity. Deletion of LdSIR2RP2
      resulted in increased sensitivity of the parasites to the known SIR2 inhibitors.
      The sirtuin inhibitors inhibited the ADP-ribosyltransferase activity of
      recombinant LdSIR2RP2. In conclusion, sirtuins could be used as potential new
      drug targets for visceral leishmaniasis.

PMID- 28493890
TI  - Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr
      virus-associated gastric carcinomas.
AB  - Multiple human diseases including cancer have been associated with a
      dysregulation in RNA splicing patterns. In the current study, modifications to
      the global RNA splicing landscape of cellular genes were investigated in the
      context of Epstein-Barr virus-associated gastric cancer. Global alterations to
      the RNA splicing landscape of cellular genes was examined in a large-scale screen
      from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing
      data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were
      also used to experimentally validate and investigate the differential alternative
      splicing (AS) events that were observed through RNA-seq studies. Our study
      identifies alterations in the AS patterns of approximately 900 genes such as
      tumor suppressor genes, transcription factors, splicing factors, and kinases.
      These findings allowed the identification of unique gene signatures for which AS
      is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV
      negative gastric cancer. Moreover, we show that the expression of Epstein-Barr
      nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular
      genes and that the EBNA1 protein interacts with cellular splicing factors. These
      findings provide insights into the molecular differences between various types of
      gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of
      cellular AS.

PMID- 28493892
TI  - HIV infection as vascular risk: A systematic review of the literature and meta
      analysis.
AB  - IMPORTANCE: The vascular risk attributable to HIV infection is rising. The
      heterogeneity of the samples studied is an obstacle to understanding whether HIV
      is a vascular risk across geographic regions. OBJECTIVE: To test the hypothesis
      that HIV infection is a vascular risk factor, and that the risk conferred by HIV
      varies by geographical region. DATA SOURCES: A systematic search of publications
      was carried out in seven electronic databases: PubMed, The Cochrane Library,
      EMBASE, Web of Science, LILACS, ClinicalTrials.gov, and WHO International
      Clinical Trials Registry Platform from inception to July 2015. STUDY SELECTION:
      We included longitudinal studies of HIV+ individuals and their risk of vascular
      outcomes of >= 50 HIV+ cases and excluded studies on biomarkers of vascular
      disease as well as clinical trials. DATA EXTRACTION AND SYNTHESIS: Data was
      extracted by one of the authors and independently confirmed by the other two
      authors. We used incidence rate (IR), incidence risk ratio (IRR) and hazard ratio
      (HR) with their 95% confidence intervals as measures of risk. MAIN OUTCOME: All
      death, myocardial infarction (MI), coronary heart disease (CHD), any stroke,
      ischemic stroke (IS) or intracranial hemorrhage (ICH). RESULTS: We screened
      11,482 references for eligibility, and selected 117 for analysis. Forty-four
      cohorts represented 334,417 HIV+ individuals, 49% from the United States.
      Compared with their European counterparts, HIV+ individuals in the United States
      had higher IR of death (IRR 1.78, 1.69-1.88), MI (IRR 1.61, 1.29-2.01), CHD (IRR
      2.27, 1.92-2.68), any stroke (IRR 1.94, 1.59-2.38), IS (IRR 1.56, 1.23-1.98), and
      ICH (IRR 4.03, 2.72-6.14). Compared with HIV- controls and independent of
      geographical region, HIV was a risk for death (HR 4.77, 4.55-5.00), MI (HR 1.60,
      1.49-1.72), any CHD (HR 1.20, 1.15-1.25), any stroke (HR 1.82, 1.53-2.16), IS (HR
      1.27, 1.15-1.39) and ICH (HR 2.20, 1.61-3.02). Use of antiretroviral therapy was
      a consistent risk for cardiac outcomes, while immunosuppression and unsuppressed
      viral load were consistent risks for cerebral outcomes. CONCLUSIONS: HIV should
      be considered a vascular risk, with varying magnitudes across geographical and
      anatomical regions. We think that strategies to reduce the HIV-related vascular
      burden are urgent, and should incorporate the disparities noted here.

PMID- 28493893
TI  - Comparison of influencing factors on outcomes of single and multiple road traffic
      injuries: A regional study in Shanghai, China (2011-2014).
AB  - INTRODUCTION: To identify key intervention factors and reduce road traffic injury
      (RTI)-associated mortality, this study compared outcomes and influencing factors
      of single and multiple road traffic injuries (RTIs) in Shanghai. METHODS: Based
      on the design of National Trauma Data Bank, this study collected demographic,
      injury, and outcome data from RTI patients treated at the four largest trauma
      centers in Shanghai from January 2011 to January 2015. Data were analyzed with
      descriptive statistics, univariate analysis, and hierarchical logistic regression
      analysis. RESULTS: Among 2397 participants, 59.4% had a single injury, and 40.6%
      had multiple injuries. Most patients' outcome was cure or improvement. For single
      RTI patients, length of stay, body region, central nervous system injury, acute
      renal failure, multiple organ dysfunction syndrome, bacterial infection, and coma
      were significantly related to outcome. For multiple-RTI patients, age, admission
      pathway, prehospital time, length of stay, number of body regions, body region,
      injury condition, injury severity score, and coma were significantly related to
      outcome. CONCLUSIONS: Emergency rescue in road traffic accidents should focus on
      high-risk groups (the elderly), high-incidence body regions (head, thorax,
      pelvis) and number of injuries, injury condition (central nervous system injury,
      coma, complications, admission pathway), injury severity (critically injured
      patients), and time factors (particularly prehospital time).

PMID- 28493894
TI  - Multi-scale temporal patterns in fish presence in a high-velocity tidal channel.
AB  - The natural variation of fish presence in high-velocity tidal channels is not
      well understood. A better understanding of fish use of these areas would aid in
      predicting fish interactions with marine hydrokinetic (MHK) devices, the effects
      of which are uncertain but of high concern. To characterize the patterns in fish
      presence at a tidal energy site in Cobscook Bay, Maine, we examined two years of
      hydroacoustic data continuously collected at the proposed depth of an MHK turbine
      with a bottom-mounted, side-looking echosounder. The maximum number of fish
      counted per hour ranged from hundreds in the early spring to over 1,000 in the
      fall. Counts varied greatly with tidal and diel cycles in a seasonally changing
      relationship, likely linked to the seasonally changing fish community of the bay.
      In the winter and spring, higher hourly counts were generally confined to ebb
      tides and low slack tides near sunrise and sunset. In summer and fall of each
      year, the highest fish counts shifted to night and occurred during ebb, low
      slack, and flood tides. Fish counts were not linked to current speed, and did not
      decrease as current speed increased, contrary to observations at other tidal
      power sites. As fish counts may be proportional to the encounter rate of fish
      with an MHK turbine at the same depth, highly variable counts indicate that the
      risk to fish is similarly variable. The links between fish presence and
      environmental cycles at this site will likely be present at other locations with
      similar environmental forcing, making these observations useful in predicting
      potential fish interactions at tidal energy sites worldwide.

PMID- 28493891
TI  - Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2
      infection in HSV-2 seronegative women.
AB  - BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX(r)
      B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination.
      The bivalent AIDSVAX(r) B/E vaccine contains two gp120 envelope glycoproteins,
      one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244
      isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV
      1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV
      2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected
      females against HSV-2 acquisition in RV144. METHODS: Of the women enrolled in
      RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected
      according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis.
      Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding
      antibody multiplex assay and HSV-2 serostatus was determined by Western blot
      analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG
      and IgA responses two weeks post last vaccination, respectively. There was no
      evidence of reduction in HSV-2 infection by vaccination compared to placebo
      recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in
      individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2
      indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the
      vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect
      subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2
      infection by Week 78 for female placebo recipients who were baseline HSV-1
      positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66
      to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection
      by vaccination was detected. CONCLUSIONS: AIDSVAX(r) B/E containing gD did not
      confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite
      eliciting anti-gD serum antibodies.

PMID- 28493895
TI  - The cardiac glycoside ouabain activates NLRP3 inflammasomes and promotes cardiac
      inflammation and dysfunction.
AB  - Cardiac glycosides such as digoxin are Na+/K+-ATPase inhibitors that are widely
      used for the treatment of chronic heart failure and cardiac arrhythmias; however,
      recent epidemiological studies have suggested a relationship between digoxin
      treatment and increased mortality. We previously showed that nucleotide-binding
      oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)
      inflammasomes, which regulate caspase-1-dependent interleukin (IL)-1beta release,
      mediate the sterile cardiovascular inflammation. Because the Na+/K+-ATPase is
      involved in inflammatory responses, we investigated the role of NLRP3
      inflammasomes in the pathophysiology of cardiac glycoside-induced cardiac
      inflammation and dysfunction. The cardiac glycoside ouabain induced cardiac
      dysfunction and injury in wild-type mice primed with a low dose of
      lipopolysaccharide (LPS), although no cardiac dysfunction was observed in mice
      treated with either ouabain or LPS alone. Ouabain also induced cardiac
      inflammatory responses, such as macrophage infiltration and IL-1beta release,
      when mice were primed with LPS. These cardiac manifestations were all
      significantly attenuated in mice deficient in IL-1beta. Furthermore, deficiency
      of NLRP3 inflammasome components, NLRP3 and caspase-1, also attenuated ouabain
      induced cardiac dysfunction and inflammation. In vitro experiments revealed that
      ouabain induced NLRP3 inflammasome activation as well as subsequent IL-1beta
      release from macrophages, and this activation was mediated by K+ efflux. Our
      findings demonstrate that cardiac glycosides promote cardiac inflammation and
      dysfunction through NLRP3 inflammasomes and provide new insights into the
      mechanisms underlying the adverse effects of cardiac glycosides.

PMID- 28493896
TI  - Candidemia in the elderly: What does it change?
AB  - BACKGROUND: Candidemia is a life-threatening fungal infection and it can affect
      patients of all ages. Characterization of candidemia in the elderly is lacking.
      METHODS: We performed a retrospective study of adults (>= 18 years) with
      candidemia diagnosed in our center in 2010-2015. Demographics, comorbidities,
      clinical and microbiologic characteristics, antifungal treatment and outcome were
      compared between older (<=65 years) and younger (>65 years) patients. RESULTS:
      Among 302 patients with candidemia identified during the study period, 188 (62%)
      belonged to the elderly group. Comorbidities were significantly more frequent in
      older patients and included chronic pulmonary diseases, cardiovascular diseases,
      diabetes mellitus, and chronic renal failure (p ranging from <0.0001 to 0.017). A
      significantly higher proportion of older patients had septic shock (p = 0.040) at
      the time of candidemia. Candida albicans accounted for 53% of isolates and there
      were no significant differences between patients' age and Candida species. Thirty
      day mortality was significantly higher in older (45%) than in younger (28%)
      patients (p = 0.003). Factors associated with a significant higher proportion of
      death in the elderly included older age (i.e.: old-old), being hospitalized in
      ICU rather than in other wards, suffering from chronic pulmonary diseases, the
      presence of septic shock, multiple organ failure, dialysis and being infected
      with C. glabrata (p ranging from <0.0001 to 0.034). On multivariate analysis
      septic shock (HR 1.744 [CI95% 1.049-2.898], p = 0.032) and multiple organ failure
      (HR 2.242 [CI95% 1.070-4.698], p = 0.032) were independently associated with a
      higher risk of death. The probability of 30-days survival of older patients was
      significantly reduced when compared to that of younger patients (p = 0.005) who
      did not receive any treatment. In the elderly, there was a trend toward higher
      MICs for fluconazole/C. albicans, fluconazole/C. glabrata, amphotericin B/C.
      albicans, and caspofungin/C. glabrata. CONCLUSIONS: In our study, we found that
      elderly patients with Candida bloodstream infections are characterized by a high
      mortality rate. In particular, the lack of any antifungal therapy as well as the
      occurrence of septic shock increased significantly the overall mortality.
      Additionally, we found that there was a trend of higher MIC for specific
      drug/Candida combination.

PMID- 28493897
TI  - Characterization of a Bvg-regulated fatty acid methyl-transferase in Bordetella
      pertussis.
AB  - The whooping cough agent Bordetella pertussis controls the expression of its
      large virulence regulon in a coordinated manner through the two-component signal
      transduction system BvgAS. In addition to the genes coding for bona fide
      virulence factors, the Bvg regulon comprises genes of unknown function. In this
      work, we characterized a new Bvg-activated gene called BP2936. Homologs of BP2936
      are found in other pathogenic Bordetellae and in several other species, including
      plant pathogens and environmental bacteria. We showed that the gene product of
      BP2936 is a membrane-associated methyl-transferase of free fatty acids. We thus
      propose to name it FmtB, for fatty acid methyl-transferase of Bordetella. The
      role of this protein was tested in cellular and animal models of infection, but
      the loss of BP2936 did not appear to affect host-pathogen interactions in those
      assays. The high level of conservation of BP2936 among B. pertussis isolates
      nevertheless argues that it probably plays a role in the life cycle of this
      pathogen.

PMID- 28493898
TI  - Apathy, but not depression, is associated with executive dysfunction in cerebral
      small vessel disease.
AB  - OBJECTIVE: To determine the prevalence of apathy and depression in cerebral small
      vessel disease (SVD), and the relationships between both apathy and depression
      with cognition. To examine whether apathy is specifically related to impairment
      in executive functioning and processing speed. METHODS: 196 patients with a
      clinical lacunar stroke and an anatomically corresponding lacunar infarct on MRI
      were compared to 300 stroke-free controls. Apathy and depression were measured
      using the Geriatric Depression Scale, and cognitive functioning was assessed
      using an SVD cognitive screening tool, the Brief Memory and Executive Test, which
      measures executive functioning/processing speed and memory/orientation. Path
      analysis and binary logistic regression were used to assess the relation between
      apathy, depression and cognitive impairment. RESULTS: 31 participants with SVD
      (15.8%) met criteria for apathy only, 23 (11.8%) for both apathy and depression,
      and 2 (1.0%) for depression only. In the SVD group the presence of apathy was
      related to global cognition, and specifically to impaired executive
      functioning/processing speed, but not memory/orientation. The presence of
      depression was not related to global cognition, impaired executive
      functioning/processing speed or memory/orientation. CONCLUSIONS: Apathy is a
      common feature of SVD and is associated with impaired executive
      functioning/processing speed suggesting the two may share biological mechanisms.
      Screening for apathy should be considered in SVD, and further work is required to
      develop and evaluate effective apathy treatment or management in SVD.

PMID- 28493899
TI  - Distinct behavioral and brain changes after different durations of the modified
      multiple platform method on rats: An animal model of central fatigue.
AB  - The modified multiple platform method (MMPM) is a classical sleep deprivation
      model. It has been widely used in behavioral and brain research, due to its
      effects on physical and mental functions. However, different MMPM protocols can
      promote distinct effects in rats. Although the MMPM has been proved to induce
      central fatigue, the effects of different durations of subjection to the MMPM
      remain undetermined. This study aims to investigate the changes in behavior, N
      Methyl-d-Aspartate receptor 1 (NR1) and 2A (NR2A), as well as the ultrastructural
      alteration in the hippocampus after different MMPM modelling, to compare the
      central fatigue effect induced by dynamic MMPM. Rats were randomly divided into
      four groups: 5-, 14- and 21- day MMPM groups, and a control group. Each MMPM
      group underwent a 14-hour daily MMPM modelling. After each training session, open
      field and elevated plus maze tests were performed. Corticosterone levels were
      detected by ELISA, and the hippocampal NR1 and NR2A were measured by RT-PCR and
      Western blot analysis. In addition, ultrastructural changes in the hippocampal
      cornu ammonis 1(CA1) region were determined by transmission electron microscopy
      (TEM). The findings showed that the 5 and 14 days of MMPM induced a high-stress
      state, while the 21 days of MMPM induced anxiety and degenerative alteration in
      the hippocampal morphology. Additionally, hippocampal NR1 and NR2A gene
      expression decreased in all MMPM groups, whereas the protein expression only
      decreased in the 21-day group. Overall, different durations of MMPM caused
      distinct behavioral and brain changes, and the 21 days of MMPM could induce
      central fatigue.

PMID- 28493901
TI  - The feasibility of local participation in Measuring, Reporting and Verification
      (PMRV) for REDD.
AB  - The studies in this PLOS ONE collection investigated the feasibility of community
      participation in Measuring, Reporting and Verifying (Participatory MRV-PMRV)
      initiatives in the context of national programs to reduce emissions from
      deforestation and forest degradation (REDD+). While such participation is
      desirable, its feasibility has been uncertain. This collection builds the
      empirical foundations for putting PMRV into practice. The authors of this article
      identified five crucial considerations: (1) clarify the stakeholders, (2)
      understand their motivation to participate, (3) integrate knowledge and
      information from multiple disciplines and sources, (4) convey knowledge and
      information across multiple levels of governance, and (5) clarify and enable the
      links to REDD+ safeguards. We conclude that local communities and other local
      actors can play a major role in achieving REDD+ MRV, however, this requires
      attention to their needs and motivations. Future activities should include
      assessment of past PMRV experiences, costs and benefits, operationalization of
      reporting and verification, formalization of PMRV and full scale testing on the
      ground.

PMID- 28493900
TI  - Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue
      predict later life neurological outcomes.
AB  - BACKGROUND: Preterm birth is a major risk factor for neurodevelopmental delays
      and disorders. This study aimed to identify genomic biomarkers of intrauterine
      inflammation in umbilical cord tissue in preterm neonates that predict cognitive
      impairment at 10 years of age. STUDY DESIGN: Genome-wide messenger RNA (mRNA)
      levels from umbilical cord tissue were obtained from 43 neonates born before 28
      weeks of gestation. Genes that were differentially expressed across four
      indicators of intrauterine inflammation were identified and their functions
      examined. Exact logistic regression was used to test whether expression levels in
      umbilical cord tissue predicted neurocognitive function at 10 years of age.
      RESULTS: Placental indicators of inflammation were associated with changes in the
      mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased
      expression showed significant enrichment for biological signaling processes
      related to neuronal development and growth. The altered expression of six genes
      was found to predict neurocognitive impairment when children were 10 years old
      These genes include two that encode for proteins involved in neuronal
      development. CONCLUSION: Prenatal intrauterine inflammation is associated with
      altered gene expression in umbilical cord tissue. A set of six of the
      differentially expressed genes predict cognitive impairment later in life,
      suggesting that the fetal environment is associated with significant adverse
      effects on neurodevelopment that persist into later childhood.

PMID- 28493902
TI  - Circulating levels of sclerostin but not DKK1 associate with laboratory
      parameters of CKD-MBD.
AB  - INTRODUCTION: Mounting evidence indicates that a disturbed Wnt-beta-catenin
      signaling may be involved in the pathogenesis of chronic kidney disease-mineral
      and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating
      levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1)
      and the relationship with laboratory parameters of CKD-MBD are incomplete.
      METHODS: We analyzed serum sclerostin and DKK1 in 308 patients across the stages
      of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage
      4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49
      healthy controls. We investigated associations with demographics, renal function,
      parameters of mineral metabolism including 25(OH) vitamin D, 1,25(OH)2 vitamin D,
      biointact fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and
      bone turnover markers. RESULTS: Serum sclerostin, but not DKK1, increases in more
      advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH)2 vitamin
      D concentrations. Bone turnover markers are highest in hemodialysis patients
      presenting the combination of high PTH with low sclerostin level. Serum DKK1
      levels are lower in CKD patients than in controls and are not associated with
      laboratory parameters of mineral metabolism. Interestingly, a direct association
      between DKK1 and platelet count was observed. CONCLUSION: In CKD, serum levels of
      the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites
      of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to
      DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients.
      DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet
      counts.

PMID- 28493903
TI  - A novel multifunctional peptide oligomer of bacitracin with possible
      bioindustrial and therapeutic applications from a Korean food-source Bacillus
      strain.
AB  - CONCLUSION: CSP32 has stable characteristics and may find bio-industrial and
      therapeutic applications.

PMID- 28493904
TI  - Factors associated with help-seeking behaviour among individuals with major
      depression: A systematic review.
AB  - Psychological models can help to understand why many people suffering from major
      depression do not seek help. Using the 'Behavioral Model of Health Services Use',
      this study systematically reviewed the literature on the characteristics
      associated with help-seeking behaviour in adults with major depression. Articles
      were identified by systematically searching the MEDLINE, EMBASE and PsycInfo
      databases and relevant reference lists. Observational studies investigating the
      associations between individual or contextual characteristics and professional
      help-seeking behaviour for emotional problems in adults formally diagnosed with
      major depression were included. The quality of the included studies was assessed,
      and factors associated with help-seeking behaviour were qualitatively
      synthesized. In total, 40 studies based on 26 datasets were included. Several
      studies investigated predisposing (age (N = 17), gender (N = 16), ethnicity (N =
      9), education (N = 11), marital status (N = 12)), enabling (income (N = 12)),
      need (severity (N = 14), duration (N = 9), number of depressive episodes (N = 6),
      psychiatric comorbidity (N = 10)) and contextual factors (area (N = 8)). Socio
      demographic and need factors appeared to influence help-seeking behaviour.
      Although existing studies provide insight into the characteristics associated
      with help seeking for major depression, cohort studies and research on beliefs
      about, barriers to and perceived need for treatment are lacking. Based on this
      review, interventions to increase help-seeking behaviour can be designed.

PMID- 28493906
TI  - A diffusion based study of population dynamics: Prehistoric migrations into South
      Asia.
AB  - A diffusion equation has been used to study migration of early humans into the
      South Asian subcontinent. The diffusion equation is tempered by a set of
      parameters that account for geographical features like proximity to water
      resources, altitude, and flatness of land. The ensuing diffusion of populations
      is followed in time-dependent computer simulations carried out over a period of
      10,000 YBP. The geographical parameters are determined from readily-available
      satellite data. The results of our computer simulations are compared to recent
      genetic data so as to better correlate the migratory patterns of various
      populations; they suggest that the initial populations started to coalesce around
      4,000 YBP before the commencement of a period of relative geographical isolation
      of each population group. The period during which coalescence of populations
      occurred appears consistent with the established timeline associated with the
      Harappan civilization and also, with genetic admixing that recent genetic mapping
      data reveal. Our results may contribute to providing a timeline for the movement
      of prehistoric people. Most significantly, our results appear to suggest that the
      Ancestral Austro-Asiatic population entered the subcontinent through an easterly
      direction, potentially resolving a hitherto-contentious issue.

PMID- 28493907
TI  - Edema is not a reliable diagnostic sign to exclude small brain metastases.
AB  - No prior systematic study on the extent of vasogenic edema (VE) in patients with
      brain metastases (BM) exists. Here, we aim to determine 1) the general volumetric
      relationship between BM and VE, 2) a threshold diameter above which a BM shows
      VE, and 3) the influence of the primary tumor and location of the BM in order to
      improve diagnostic processes and understanding of edema formation. This single
      center, retrospective study includes 173 untreated patients with histologically
      proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted
      images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images
      was conducted. Statistical analyses were performed using a paired-samples t-test,
      linear regression/generalized mixed-effects model, and receiver-operating
      characteristic (ROC) curve controlling for the possible effect of non-uniformly
      distributed metastases among patients. For BM with non-confluent edema (n = 545),
      there was a statistically significant positive correlation between the volumes of
      the BM and the VE (P < 0.001). The optimal threshold for edema formation was a
      diameter of 9.4 mm for all BM. The primary tumors as interaction term in
      multivariate analysis had a significant influence on VE formation whereas
      location had not. Hence VE development is dependent on the volume of the
      underlying BM and the site of the primary neoplasm, but not from the location of
      the BM.

PMID- 28493908
TI  - Missed diagnostic opportunities within South Africa's early infant diagnosis
      program, 2010-2015.
AB  - BACKGROUND: Samples submitted for HIV PCR testing that fail to yield a positive
      or negative result represent missed diagnostic opportunities. We describe HIV PCR
      test rejections and indeterminate results, and the associated delay in diagnosis,
      within South Africa's early infant diagnosis (EID) program from 2010 to 2015.
      METHODS: HIV PCR test data from January 2010 to December 2015 were extracted from
      the National Health Laboratory Service Corporate Data Warehouse, a central data
      repository of all registered test-sets within the public health sector in South
      Africa, by laboratory number, result, date, facility, and testing laboratory.
      Samples that failed to yield either a positive or negative result were
      categorized according to the rejection code on the laboratory information system,
      and descriptive analysis performed using Microsoft Excel. Delay in diagnosis was
      calculated for patients who had a missed diagnostic opportunity registered
      between January 2013 and December 2015 by means of a patient linking-algorithm
      employing demographic details. RESULTS: Between 2010 and 2015, 2 178 582 samples
      were registered for HIV PCR testing of which 6.2% (n = 134 339) failed to yield
      either a positive or negative result, decreasing proportionally from 7.0% (n = 20
      556) in 2010 to 4.4% (n = 21 388) in 2015 (p<0.001). Amongst 76 972 coded missed
      diagnostic opportunities, 49 585 (64.4%) were a result of pre-analytical error
      and 27 387 (35.6%) analytical error. Amongst 49 694 patients searched for follow
      up results, 16 895 (34.0%) had at least one subsequent HIV PCR test registered
      after a median of 29 days (IQR: 13-57), of which 8.4% tested positive compared
      with 3.6% of all samples submitted for the same period. CONCLUSIONS: Routine
      laboratory data provides the opportunity for near real-time surveillance and
      quality improvement within the EID program. Delay in diagnosis and wastage of
      resources associated with missed diagnostic opportunities must be addressed and
      infants actively followed-up as South Africa works towards elimination of mother
      to-child transmission.

PMID- 28493905
TI  - Melioidosis: Clinical impact and public health threat in the tropics.
AB  - This review briefly summarizes the geographical distribution and clinical impact
      of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram
      negative bacterium) is the major causative agent for melioidosis, which is
      prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia.
      Melioidosis patients are increasingly being recognized in other parts of the
      world. The bacteria are intrinsically resistant to many antimicrobial agents, but
      prolonged treatment, especially with combinations of antibiotics, may be
      effective. Despite therapy, the overall case fatality rate of septicemia in
      melioidosis remains significantly high. Intracellular survival of the bacteria
      within macrophages may progress to chronic infections, and about 10% of patients
      suffer relapses. In the coming decades, melioidosis will increasingly afflict
      travelers throughout many global regions. Clinicians managing travelers returning
      from the subtropics or tropics with severe pneumonia or septicemia should
      consider acute melioidosis as a differential diagnosis. Patients with open skin
      wounds, diabetes, or chronic renal disease are at higher risk for melioidosis and
      should avoid direct contact with soil and standing water in endemic regions.
      Furthermore, there are fears that B. pseudomallei may be used as a biological
      weapon. Technological advancements in molecular diagnostics and antibiotic
      therapy are improving the disease outcomes in endemic areas throughout Asia.
      Research and development efforts on vaccine candidates against melioidosis are
      ongoing.

PMID- 28493909
TI  - HNF1alpha defect influences post-prandial lipid regulation.
AB  - PURPOSE: Hepatocyte nuclear factor 1 alpha (HNF1alpha) defects cause Mature Onset
      Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell
      insulin secretion. However, HNF1alpha is involved in many other metabolic
      pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to
      investigate gut hormones, lipids, and insulin regulation in response to a meal
      test in HNF1alpha defect carriers (MODY3) compared to non-diabetic subjects
      (controls) and type 2 diabetes (T2D). METHODS: We administered a standardized
      liquid meal to each participant. Over 6 hours, we measured post-meal responses of
      insulin regulation (blood glucose, c-peptide, insulin), gut hormones (ghrelin,
      glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1) and lipids
      (non-esterified fatty acids [NEFA] and triglycerides). RESULTS: We found that
      MODY3 participants had lower insulin secretion indices than controls and T2D
      participants, showing the expected beta-cell defect. MODY3 had similar glycated
      hemoglobin levels (HbA1c median [IQR]: 6.5 [5.6-7.6]%) compared to T2D (median:
      6.6 [6.2-6.9]%; P<0.05). MODY3 had greater insulin sensitivity (Matsuda index:
      71.9 [29.6; 125.5]) than T2D (3.2 [4.0; 6.0]; P<0.05). MODY3 experienced a larger
      decrease in the ratio of NEFA to insulin (NEFA 30-0 / insulin 30-0: -39 [-78; 
      30] x104) in the early post-prandial period (0-30 minutes) compared to controls
      and to T2D (-2.0 [-0.6; -6.4] x104; P<0.05). MODY3 had lower fasting (0.66 [0.46;
      1.2] mM) and post-meal triglycerides levels compared to T2D (fasting: 2.3 [1.7;
      2.7] mM; P<0.05). We did not detect significant post-meal differences in ghrelin
      and incretins between MODY3 and other groups. CONCLUSION: In response to a
      standard meal test, MODY3 showed greater early post-prandial NEFA diminution in
      response to relatively low early insulin secretion, and they maintained very low
      post-prandial triglycerides levels.

PMID- 28493910
TI  - A new two-stage method for revealing missing parts of edges in protein-protein
      interaction networks.
AB  - With the increasing availability of high-throughput data, various computational
      methods have recently been developed for understanding the cell through protein
      protein interaction (PPI) networks at a systems level. However, due to the
      incompleteness of the original PPI networks those efforts have been significantly
      hindered. In this paper, we propose a two stage method to predict underlying
      links between two originally unlinked protein pairs. First, we measure gene
      expression and gene functional similarly between unlinked protein pairs on
      Saccharomyces cerevisiae benchmark network and obtain new constructed networks.
      Then, we select the significant part of the new predicted links by analyzing the
      difference between essential proteins that have been identified based on the new
      constructed networks and the original network. Furthermore, we validate the
      performance of the new method by using the reliable and comprehensive PPI dataset
      obtained from the STRING database and compare the new proposed method with four
      other random walk-based methods. Comparing the results indicates that the new
      proposed strategy performs well in predicting underlying links. This study
      provides a general paradigm for predicting new interactions between protein pairs
      and offers new insights into identifying essential proteins.

PMID- 28493911
TI  - Long-term fertilization determines different metabolomic profiles and responses
      in saplings of three rainforest tree species with different adult canopy
      position.
AB  - BACKGROUND: Tropical rainforests are frequently limited by soil nutrient
      availability. However, the response of the metabolic phenotypic plasticity of
      trees to an increase of soil nutrient availabilities is poorly understood. We
      expected that increases in the ability of a nutrient that limits some plant
      processes should be detected by corresponding changes in plant metabolome profile
      related to such processes. METHODOLOGY/PRINCIPAL FINDINGS: We studied the foliar
      metabolome of saplings of three abundant tree species in a 15 year field NPK
      fertilization experiment in a Panamanian rainforest. The largest differences were
      among species and explained 75% of overall metabolome variation. The saplings of
      the large canopy species, Tetragastris panamensis, had the lowest concentrations
      of all identified amino acids and the highest concentrations of most identified
      secondary compounds. The saplings of the "mid canopy" species, Alseis blackiana,
      had the highest concentrations of amino acids coming from the biosynthesis
      pathways of glycerate-3P, oxaloacetate and alpha-ketoglutarate, and the saplings
      of the low canopy species, Heisteria concinna, had the highest concentrations of
      amino acids coming from the pyruvate synthesis pathways.
      CONCLUSIONS/SIGNIFICANCE: The changes in metabolome provided strong evidence that
      different nutrients limit different species in different ways. With increasing P
      availability, the two canopy species shifted their metabolome towards larger
      investment in protection mechanisms, whereas with increasing N availability, the
      sub-canopy species increased its primary metabolism. The results highlighted the
      proportional distinct use of different nutrients by different species and the
      resulting different metabolome profiles in this high diversity community are
      consistent with the ecological niche theory.

PMID- 28493912
TI  - Effects of intensity and amount of exercise on measures of insulin and glucose:
      Analysis of inter-individual variability.
AB  - AIM: To determine the separate effects of exercise amount and intensity on the
      rate of response for glucose and insulin variables, where rate of response was
      defined as the number of individuals with improvement in glucose and insulin
      values that was beyond the day-to-day variability of measurement. METHODS:
      Participants were 171 sedentary, middle-aged abdominally obese adults who
      completed a 24-week intervention. Participants were randomly assigned to (1) no
      exercise control (n = 51), (2) low-amount, low-intensity exercise (LALI, n = 38),
      (3) high-amount, low-intensity exercise (HALI, n = 52), or (4) high-amount, high
      intensity exercise (HAHI, n = 30). Two-hour glucose, insulin area under the curve
      (AUC), and fasting insulin were measured during a 2-hour, 75g oral glucose
      challenge. The day-to-day variability for these measures was calculated to be +/
      2.2 mmol/L, +/-940.2 pmol/L, and +/-38.9 pmol/L, respectively. RESULTS: At 24
      weeks, the number of nonresponders for 2-hr glucose was 98.0%, 86.8%, 94.2%,
      86.7% in the control, LALI, HALI, and HAHI groups, respectively. The number of
      nonresponders for insulin AUC was 88.0%, 75.7%, 75.0%, 80.0% in the control,
      LALI, HALI, and HAHI groups, respectively. The number of nonresponders for
      fasting insulin was 88.2%, 84.2%, 84.6%, 93.3% in the control, LALI, HALI, and
      HAHI groups, respectively. The rate of response was not different between control
      and any of the exercise groups for any measure (p>0.05). CONCLUSION: The
      improvement in glucose and insulin measures did not exceed the day-to-day
      variability of measurement for approximately 80% of the participants independent
      of exercise amount or intensity.

PMID- 28493914
TI  - Take me where I want to go: Institutional prestige, advisor sponsorship, and
      academic career placement preferences.
AB  - Placement in prestigious research institutions for STEM (science, technology,
      engineering, and mathematics) PhD recipients is generally considered to be
      optimal. Yet some doctoral recipients are not interested in intensive research
      careers and instead seek alternative careers, outside but also within academe
      (for example teaching positions in Liberal Arts Schools). Recent attention to non
      academic pathways has expanded our understanding of alternative PhD careers.
      However, career preferences and placements are also nuanced along the academic
      pathway. Existing research on academic careers (mostly research-centric) has
      found that certain factors have a significant impact on the prestige of both the
      institutional placement and the salary of PhD recipients. We understand less,
      however, about the functioning of career preferences and related placements
      outside of the top academic research institutions. Our work builds on prior
      studies of academic career placement to explore the impact that prestige of PhD
      granting institution, advisor involvement, and cultural capital have on the
      extent to which STEM PhDs are placed in their preferred academic institution
      types. What determines whether an individual with a preference for research
      oriented institutions works at a Research Extensive university? Or whether an
      individual with a preference for teaching works at a Liberal Arts college? Using
      survey data from a nationally representative sample of faculty in biology,
      biochemistry, civil engineering and mathematics at four different Carnegie
      Classified institution types (Research Extensive, Research Intensive, Master's I
      & II, and Liberal Arts Colleges), we examine the relative weight of different
      individual and institutional characteristics on institutional type placement. We
      find that doctoral institutional prestige plays a significant role in matching
      individuals with their preferred institutional type, but that advisor involvement
      only has an impact on those with a preference for research oriented institutions.
      Gender effects are also observed, particularly in the role of the advisor in
      affecting preferred career placement.

PMID- 28493915
TI  - An African grassland responds similarly to long-term fertilization to the Park
      Grass experiment.
AB  - We compared the results of a long-term (65 years) experiment in a South African
      grassland with the world's longest-running ecological experiment, the Park Grass
      study at Rothamsted, U.K. The climate is warm and humid in South Africa and cool
      and temperate in England. The African grassland has been fertilized with two
      forms of nitrogen applied at four levels, phosphorus and lime in a crossed design
      in 96 plots. In 1951, about 84% of plant cover consisted of Themeda triandra,
      Tristachya leucothrix and Setaria nigrirostris. Currently, the dominant species
      are Panicum maximum, Setaria sphacelata and Eragrostis curvula, making up 71% of
      total biomass. As in the Park Grass experiment, we found a significant (additive)
      interaction effect on ANPP of nitrogen and phosphorus, and a (marginally
      significant) negative correlation between ANPP and species richness. Unlike the
      Park Grass experiment, there was no correlation between ANPP and species richness
      when pH was included as a covariate. There was also a significant negative effect
      of nitrogen amount and nitrogen form and a positive effect of lime on species
      richness and species diversity. Soil pH had an important effect on species
      richness. Liming was insufficient to balance the negative effects on species
      richness of nitrogen fertilization. There was a significant effect of pH on
      biomass of three abundant species. There were also significant effects of light
      on the biomass of four species, with only Panicum maximum having a negative
      response to light. In all of the abundant species, adding total species richness
      and ANPP to the model increased the amount of variance explained. The biomass of
      Eragrostis curvula and P. maximum were negatively correlated with species
      richness while three other abundant species increased with species richness,
      suggesting that competition and facilitation were active. Consistent with the
      results from the Park Grass and other long-term fertilization experiments of
      grasslands, we found a positive effect of soil pH and a negative effect of
      nitrogen amount on species richness, a more acutely negative effect on species
      richness of acidic ammonium sulphate fertilizer than limestone ammonium nitrate,
      a negative relationship between species richness and biomass, and a positive
      effect on species richness of lime interacting with nitrogen.

PMID- 28493913
TI  - Pathogenic variants screening in seventeen candidate genes on 2p15 for
      association with ankylosing spondylitis in a Han Chinese population.
AB  - OBJECTIVES: Previous studies have found the association between rs10865331 in
      2p15 area and ankylosing spondylitis (AS). This study aimed to identify
      additional functional genetic variants in 2p15 region associated with AS
      susceptibility. METHODS: We used next generation sequencing (NGS) in 100 AS cases
      and 100 healthy controls to screen AS susceptible genetic variants, and validated
      these variants in 620 cases and 620 controls by using imLDRTM technique for
      single nucleotide polymorphism (SNP) genotyping. RESULTS: Totally, we identified
      12 SNPs that might confer susceptibility to AS. Of those SNPs, three (rs14170,
      rs2123111 and rs1729674) were nominally associated (P<0.05) with AS, but were no
      longer statistically significant after Bonferroni correction. After stratified by
      gender, another two SNPs (rs11428092 and rs10208769 in USP34) were associated
      with AS in males but not females, though this was not statistically significant
      after Bonferroni correction. In addition, rs1729674, rs14170, rs2123111 and
      rs10208769 were in strong linkage disequilibrium (LD) and were further enrolled
      in haplotype analysis. A novel haplotype TAGA was found to be associated with a
      decreased risk of AS (odds ratio (OR) (95% confidence interval (CI)) = 0.832
      (0.705-0.982)). Beyond that, we also demonstrated a strong relationship between
      rs10865331 and AS susceptibility (OR (95% CI) = 1.303(1.111-1.526)). CONCLUSIONS:
      rs14170 and rs2123111 inUSP34 and rs1729674 in C2orf74 may be associated with AS
      susceptibility in Han Chinese population. USP34 and C2orf74 in 2p15 region may be
      AS novel susceptibility genes.

PMID- 28493916
TI  - Vesicular glutamate transporters play a role in neuronal differentiation of
      cultured SVZ-derived neural precursor cells.
AB  - The role of glutamate in the regulation of neurogenesis is well-established, but
      the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid
      transporters (EAATs) in controlling adult neurogenesis is unknown. Here we
      investigated the implication of VGLUTs in the differentiation of subventricular
      zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs
      express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression
      increases during differentiation closely associated with the expression of marker
      genes. In expression analyses we show that VGLUT1 and VGLUT2 are preferentially
      expressed by cultured SVZ-derived doublecortin+ neuroblasts, while VGLUT3 is
      found on GFAP+ glial cells. In cultured NPCs, inhibition of VGLUT by Evans Blue
      increased the mRNA level of neuronal markers doublecortin, B3T and MAP2, elevated
      the number of NPCs expressing doublecortin protein and promoted the number of
      cells with morphological appearance of branched neurons, suggesting that VGLUT
      function prevents neuronal differentiation of NPCs. This survival- and
      differentiation-promoting effect of Evans blue was corroborated by increased AKT
      phosphorylation and reduced MAPK phosphorylation. Thus, under physiological
      conditions, VGLUT1-3 inhibition, and thus decreased glutamate exocytosis, may
      promote neuronal differentiation of NPCs.

PMID- 28493917
TI  - The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling
      study on people who inject drugs in Ho Chi Minh City, Vietnam.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)
      coinfection is a major global health problem especially among people who inject
      drugs (PWID), with significant clinical implications. Mathematical models have
      been used to great effect to shape HIV care, but few have been proposed for
      HIV/HCV. METHODS: We constructed a deterministic compartmental ODE model that
      incorporated layers for HIV disease progression, HCV disease progression and PWID
      demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT)
      scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment
      roll-out was modeled beginning in 2026, after a variety of MMT scale-up
      scenarios, and projected forward 10 years. RESULTS: Our results indicate that
      scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up
      has an impact on incidence of both infections. HCV treatment roll-out has a
      measurable impact on reductions of deaths, increasing multifold the mortality
      reductions afforded by just ART/MMT scale-ups. CONCLUSION: HCV treatment roll-out
      can have major and long-lasting effects on averting PWID deaths on top of those
      averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV
      interventions is critical in Vietnam.

PMID- 28493918
TI  - Using null models to infer microbial co-occurrence networks.
AB  - Although microbial communities are ubiquitous in nature, relatively little is
      known about the structural and functional roles of their constituent organisms'
      underlying interactions. A common approach to study such questions begins with
      extracting a network of statistically significant pairwise co-occurrences from a
      matrix of observed operational taxonomic unit (OTU) abundances across sites. The
      structure of this network is assumed to encode information about ecological
      interactions and processes, resistance to perturbation, and the identity of
      keystone species. However, common methods for identifying these pairwise
      interactions can contaminate the network with spurious patterns that obscure true
      ecological signals. Here, we describe this problem in detail and develop a
      solution that incorporates null models to distinguish ecological signals from
      statistical noise. We apply these methods to the initial OTU abundance matrix and
      to the extracted network. We demonstrate this approach by applying it to a large
      soil microbiome data set and show that many previously reported patterns for
      these data are statistical artifacts. In contrast, we find the frequency of three
      way interactions among microbial OTUs to be highly statistically significant.
      These results demonstrate the importance of using appropriate null models when
      studying observational microbiome data, and suggest that extracting and
      characterizing three-way interactions among OTUs is a promising direction for
      unraveling the structure and function of microbial ecosystems.

PMID- 28493919
TI  - Genomic variation in Plasmodium vivax malaria reveals regions under selective
      pressure.
AB  - BACKGROUND: Although Plasmodium vivax contributes to almost half of all malaria
      cases outside Africa, it has been relatively neglected compared to the more
      deadly P. falciparum. It is known that P. vivax populations possess high genetic
      diversity, differing geographically potentially due to different vector species,
      host genetics and environmental factors. RESULTS: We analysed the high-quality
      genomic data for 46 P. vivax isolates spanning 10 countries across 4 continents.
      Using population genetic methods we identified hotspots of selection pressure,
      including the previously reported MRP1 and DHPS genes, both putative drug
      resistance loci. Extra copies and deletions in the promoter region of another
      drug resistance candidate, MDR1 gene, and duplications in the Duffy binding
      protein gene (PvDBP) potentially involved in erythrocyte invasion, were also
      identified. For surveillance applications, continental-informative markers were
      found in putative drug resistance loci, and we show that organellar polymorphisms
      could classify P. vivax populations across continents and differentiate between
      Plasmodia spp. CONCLUSIONS: This study has shown that genomic diversity that lies
      within and between P. vivax populations can be used to elucidate potential drug
      resistance and invasion mechanisms, as well as facilitate the molecular barcoding
      of the parasite for surveillance applications.

PMID- 28493920
TI  - Haemolytic activity of soil from areas of varying podoconiosis endemicity in
      Ethiopia.
AB  - BACKGROUND: Podoconiosis, non-filarial elephantiasis, is a non-infectious disease
      found in tropical regions such as Ethiopia, localized in highland areas with
      volcanic soils cultivated by barefoot subsistence farmers. It is thought that
      soil particles can pass through the soles of the feet and taken up by the
      lymphatic system, leading to the characteristic chronic oedema of the lower legs
      that becomes disfiguring and disabling over time. METHODS: The close association
      of the disease with volcanic soils led us to investigate the characteristics of
      soil samples in an endemic area in Ethiopia to identify the potential causal
      constituents. We used the in vitro haemolysis assay and compared haemolytic
      activity (HA) with soil samples collected in a non-endemic region of the same
      area in Ethiopia. We included soil samples that had been previously
      characterized, in addition we present other data describing the characteristics
      of the soil and include pure phase mineral standards as comparisons. RESULTS: The
      bulk chemical composition of the soils were statistically significantly different
      between the podoconiosis-endemic and non-endemic areas, with the exception of CaO
      and Cr. Likewise, the soil mineralogy was statistically significant for iron
      oxide, feldspars, mica and chlorite. Smectite and kaolinite clays were widely
      present and elicited a strong HA, as did quartz, in comparison to other mineral
      phases tested, although no strong difference was found in HA between soils from
      the two areas. The relationship was further investigated with principle component
      analysis (PCA), which showed that a combination of an increase in Y, Zr and
      Al2O3, and a concurrent increase Fe2O3, TiO2, MnO and Ba in the soils increased
      HA. CONCLUSION: The mineralogy and chemistry of the soils influenced the HA,
      although the interplay between the components is complex. Further research should
      consider the variable biopersistance, hygroscopicity and hardness of the minerals
      and further characterize the nano-scale particles.

PMID- 28493921
TI  - Mapping the emotional face. How individual face parts contribute to successful
      emotion recognition.
AB  - Which facial features allow human observers to successfully recognize expressions
      of emotion? While the eyes and mouth have been frequently shown to be of high
      importance, research on facial action units has made more precise predictions
      about the areas involved in displaying each emotion. The present research
      investigated on a fine-grained level, which physical features are most relied on
      when decoding facial expressions. In the experiment, individual faces expressing
      the basic emotions according to Ekman were hidden behind a mask of 48 tiles,
      which was sequentially uncovered. Participants were instructed to stop the
      sequence as soon as they recognized the facial expression and assign it the
      correct label. For each part of the face, its contribution to successful
      recognition was computed, allowing to visualize the importance of different face
      areas for each expression. Overall, observers were mostly relying on the eye and
      mouth regions when successfully recognizing an emotion. Furthermore, the
      difference in the importance of eyes and mouth allowed to group the expressions
      in a continuous space, ranging from sadness and fear (reliance on the eyes) to
      disgust and happiness (mouth). The face parts with highest diagnostic value for
      expression identification were typically located in areas corresponding to action
      units from the facial action coding system. A similarity analysis of the
      usefulness of different face parts for expression recognition demonstrated that
      faces cluster according to the emotion they express, rather than by low-level
      physical features. Also, expressions relying more on the eyes or mouth region
      were in close proximity in the constructed similarity space. These analyses help
      to better understand how human observers process expressions of emotion, by
      delineating the mapping from facial features to psychological representation.

PMID- 28493922
TI  - Comparison of the long-term clinical performance of a biodegradable and a
      titanium fixation system in maxillofacial surgery: A multicenter randomized
      controlled trial.
AB  - BACKGROUND: Biodegradable fixation systems could reduce or eliminate problems
      associated with titanium removal of implants in a second operation. AIM: The aim
      of this study was to compare the long-term (i.e. >5 years postoperatively)
      clinical performance of a titanium and a biodegradable system in oral and
      maxillofacial surgery. MATERIALS AND METHODS: The present multicenter Randomized
      Controlled Trial (RCT) was performed in four hospitals in the Netherlands.
      Patients treated with a bilateral sagittal split osteotomy (BSSO) and/or a Le
      Fort-I osteotomy, and those treated for fractures of the mandible, maxilla, or
      zygoma were included from December 2006 to July 2009. The patients were randomly
      assigned to either a titanium (KLS Martin) or a biodegradable group (Inion CPS).
      RESULTS: After >5 years postoperatively, plate removal was performed in 22 of the
      134 (16.4%) patients treated with titanium and in 23 of the 87 (26.4%) patients
      treated with the biodegradable system (P = 0.036, hazard ratio (HR) biodegradable
      (95% CI) = 2.0 (1.05-3.8), HR titanium = 1). Occlusion, VAS pain scores, and MFIQ
      showed good and (almost) pain free mandibular function in both groups.
      CONCLUSION: In conclusion, the performance of the Inion CPS biodegradable system
      was inferior compared to the KLS Martin titanium system regarding plate/screws
      removal in the abovementioned surgical procedures. TRIAL REGISTRATION:
      http://controlled-trials.com ISRCTN44212338.

PMID- 28493923
TI  - Brief relaxation training is not sufficient to alter tolerance to experimental
      pain in novices.
AB  - Relaxation techniques, such as deep breathing and muscle relaxation, are aspects
      common to most forms of mindfulness training. There is now an abundance of
      research demonstrating that mindfulness training has beneficial effects across a
      wide range of clinical conditions, making it an important tool for clinical
      intervention. One area of extensive research is on the beneficial effects of
      mindfulness on experiences of pain. However, the mechanisms of these effects are
      still not well understood. One hypothesis is that the relaxation components of
      mindfulness training, through alterations in breathing and muscle tension, leads
      to changes in parasympathetic and sympathetic nervous system functioning which
      influences pain circuits. The current study seeks to examine how two of the
      relaxation subcomponents of mindfulness training, deep breathing and muscle
      relaxation, influence experiences of pain in healthy individuals. Participants
      were randomized to either a 10 minute deep breathing, progressive muscle
      relaxation, or control condition after which they were exposed to a cold pain
      task. Throughout the experiment, measures of parasympathetic and sympathetic
      nervous system activity were collected to assess how deep breathing and
      progressive muscle relaxation alter physiological responses, and if these changes
      moderate any effects of these interventions on responses to pain. There were no
      differences in participants' pain tolerances or self-reported pain ratings during
      the cold pain task or in participants' physiological responses to the task.
      Additionally, individual differences in physiological functioning were not
      related to differences in pain tolerance or pain ratings. Overall this study
      suggests that the mechanisms through which mindfulness exerts its effects on pain
      are more complex than merely through physiological changes brought about by
      altering breathing or muscle tension. This indicates a need for more research
      examining the specific subcomponents of mindfulness, and how these subcomponents
      might be acting, to better understand their utility as a clinical treatment.

PMID- 28493924
TI  - Cognitive function in multiple sclerosis improves with telerehabilitation:
      Results from a randomized controlled trial.
AB  - : Cognitive impairment affects more than half of all individuals living with
      multiple sclerosis (MS). We hypothesized that training at home with an adaptive
      online cognitive training program would have greater cognitive benefit than
      ordinary computer games in cognitively-impaired adults with MS. This was a double
      blind, randomized, active-placebo-controlled trial. Participants with MS were
      recruited through Stony Brook Medicine and randomly assigned to either the
      adaptive cognitive remediation (ACR) program or active control of ordinary
      computer games for 60 hours over 12 weeks. Training was remotely-supervised and
      delivered through a study-provided laptop computer. A computer generated, blocked
      stratification table prepared by statistician provided the randomization schedule
      and condition was assigned by a study technician. The primary outcome,
      administered by study psychometrician, was measured by change in a
      neuropsychological composite measure from baseline to study end. An intent-to
      treat analysis was employed and missing primary outcome values were imputed via
      Markov Chain Monte Carlo method. Participants in the ACR (n = 74) vs. active
      control (n = 61) training program had significantly greater improvement in the
      primary outcome of cognitive functioning (mean change in composite z score+/-SD:
      0.25+/-0.45 vs. 0.09+/-0.37, p = 0.03, estimated difference = 0.16 with 95% CI:
      0.02-0.30), despite greater training time in the active control condition (mean+/
      SD:56.9 +/- 34.6 vs. 37.7 +/-23 .8 hours played, p = 0.006). This study provides
      Class I evidence that adaptive, computer-based cognitive remediation accessed
      from home can improve cognitive functioning in MS. This telerehabilitation
      approach allowed for rapid recruitment and high compliance, and can be readily
      applied to other neurological conditions associated with cognitive dysfunction.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT02141386.

PMID- 28493925
TI  - A novel Filamentous Flower mutant suppresses brevipedicellus developmental
      defects and modulates glucosinolate and auxin levels.
AB  - BREVIPEDICELLUS (BP) encodes a class-I KNOTTED1-like homeobox (KNOX)
      transcription factor that plays a critical role in conditioning a replication
      competent state in the apical meristem, and it also governs growth and cellular
      differentiation in internodes and pedicels. To search for factors that modify BP
      signaling, we conducted a suppressor screen on bp er (erecta) plants and
      identified a mutant that ameliorates many of the pleiotropic defects of the
      parent line. Map based cloning and complementation studies revealed that the
      defect lies in the FILAMENTOUS FLOWER (FIL) gene, a member of the YABBY family of
      transcriptional regulators that contribute to meristem organization and function,
      phyllotaxy, leaf and floral organ growth and polarity, and are also known to
      repress KNOX gene expression. Genetic and cytological analyses of the fil-10
      suppressor line indicate that the role of FIL in promoting growth is independent
      of its previously characterized influences on meristem identity and lateral organ
      polarity, and likely occurs non-cell-autonomously from superior floral organs.
      Transcription profiling of inflorescences revealed that FIL downregulates
      numerous transcription factors which in turn may subordinately regulate
      inflorescence architecture. In addition, FIL, directly or indirectly, activates
      over a dozen genes involved in glucosinolate production in part by activating
      MYB28, a known activator of many aliphatic glucosinolate biosynthesis genes. In
      the bp er fil-10 suppressor mutant background, enhanced expression of CYP71A13,
      AMIDASE1 (AMI) and NITRILASE genes suggest that auxin levels can be modulated by
      shunting glucosinolate metabolites into the IAA biosynthetic pathway, and
      increased IAA levels in the bp er fil-10 suppressor accompany enhanced internode
      and pedicel elongation. We propose that FIL acts to oppose KNOX1 gene function
      through a complex regulatory network that involves changes in secondary
      metabolites and auxin.

PMID- 28493926
TI  - Obesity and access to kidney transplantation in patients starting dialysis: A
      prospective cohort study.
AB  - BACKGROUND: Obesity has been linked to poor access to medical care. Although
      scientific evidence suggest that kidney transplantation improves survival and
      quality of life in obese patients with end-stage renal disease (ESRD), few data
      exist on the impact of obesity on access to kidney transplantation in this
      population. OBJECTIVES: We aimed to characterize the relationships between body
      mass index (BMI) at the start of dialysis, changes in BMI after the start of
      dialysis, and either access to kidney transplantation or overall mortality in
      dialysis or transplantation among ESRD patients. METHODS: Between 2002 and 2011,
      19524 dialysis patients with ESRD were included in the study via the French
      nationwide Renal Epidemiology and Information Network. Data on sociodemographic
      factors, comorbidities and laboratory test results were recorded upon entry into
      the registry. BMI were obtained at the start of dialysis and then yearly. Cubic
      spline regression analyses provided a graphic evaluation of the relationships
      between BMI at the start of dialysis and outcomes. Joint models were used to
      evaluate the association between the change over time in BMI and outcomes.
      RESULTS: During a median follow-up of 20.3 months, 6634 patients underwent kidney
      transplantation. A BMI >31 kg/m2 at the start of the dialysis was associated with
      a lower likelihood of receiving a kidney transplant, and the likelihood decreased
      even further with higher BMI values. For patients with BMI >=30kg/m2 at the start
      of the dialysis, a 1 kg/m2 decrease in BMI during follow-up was associated with a
      9% to 11% increase in the likelihood of receiving a transplant. There was an L
      shaped relationship between BMI at the start of dialysis and overall mortality.
      We showed that obese patients with ESRD face barriers to the receipt of a kidney
      transplant without valid reasons. CONCLUSION: Greater attention to this issue
      would improve the fairness of the organ allocation process and might improve
      outcomes for obese patients with ESRD.

PMID- 28493928
TI  - NMR quantification of diffusional exchange in cell suspensions with relaxation
      rate differences between intra and extracellular compartments.
AB  - Water transport across cell membranes can be measured non-invasively with
      diffusion NMR. We present a method to quantify the intracellular lifetime of
      water in cell suspensions with short transverse relaxation times, T2, and also
      circumvent the confounding effect of different T2 values in the intra- and
      extracellular compartments. Filter exchange spectroscopy (FEXSY) is specifically
      sensitive to exchange between compartments with different apparent diffusivities.
      Our investigation shows that FEXSY could yield significantly biased results if
      differences in T2 are not accounted for. To mitigate this problem, we propose
      combining FEXSY with diffusion-relaxation correlation experiment, which can
      quantify differences in T2 values in compartments with different diffusivities.
      Our analysis uses a joint constrained fitting of the two datasets and considers
      the effects of diffusion, relaxation and exchange in both experiments. The method
      is demonstrated on yeast cells with and without human aquaporins.

PMID- 28493927
TI  - Protective effects and functional mechanisms of Lactobacillus gasseri SBT2055
      against oxidative stress.
AB  - Lactobacillus gasseri SBT2055 (LG2055) is one of the probiotic lactic acid
      bacteria. Recently, we demonstrated that feeding with LG2055 extended the
      lifespan of Caenorhabditis elegans and that the prolongevity effect was dependent
      upon the regulation of oxidative stress response. In this study, we assessed
      whether LG2055 regulated the oxidative stress response of mammalian cells. In NIH
      3T3 cells and primary mouse embryonic fibroblast cells, low cell proliferation
      rates and high reactive oxygen species levels were observed following paraquat
      treatment. LG2055 treatment suppressed these responses in paraquat-treated cells,
      indicating that LG2055 protected against oxidative stress in mammalian cells. The
      mRNA expression of oxidative stress-related genes, total nuclear factor-erythroid
      2-related factor 2 (Nrf2) protein levels, and the nuclear translocation of Nrf2
      were increased by LG2055 treatment. These results suggested that the Nrf2
      antioxidant response element (ARE) signaling pathway was activated by LG2055.
      Furthermore, c-Jun NH2-terminal kinase (JNK) was activated by LG2055 treatment
      and the inhibition of JNK suppressed the activation of the Nrf2-ARE signaling
      pathway in LG2055-treated cells. Together, these findings suggest that LG2055
      activated the Nrf2-ARE signaling pathway by JNK activation, thus strengthening
      the defense system against oxidative stress in mammalian cells.

PMID- 28493929
TI  - Selecting the best stable isotope mixing model to estimate grizzly bear diets in
      the Greater Yellowstone Ecosystem.
AB  - Past research indicates that whitebark pine seeds are a critical food source for
      Threatened grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem
      (GYE). In recent decades, whitebark pine forests have declined markedly due to
      pine beetle infestation, invasive blister rust, and landscape-level fires. To
      date, no study has reliably estimated the contribution of whitebark pine seeds to
      the diets of grizzlies through time. We used stable isotope ratios (expressed as
      delta13C, delta15N, and delta34S values) measured in grizzly bear hair and their
      major food sources to estimate the diets of grizzlies sampled in Cooke City
      Basin, Montana. We found that stable isotope mixing models that included
      different combinations of stable isotope values for bears and their foods
      generated similar proportional dietary contributions. Estimates generated by our
      top model suggest that whitebark pine seeds (35+/-10%) and other plant foods
      (56+/-10%) were more important than meat (9+/-8%) to grizzly bears sampled in the
      study area. Stable isotope values measured in bear hair collected elsewhere in
      the GYE and North America support our conclusions about plant-based foraging. We
      recommend that researchers consider model selection when estimating the diets of
      animals using stable isotope mixing models. We also urge researchers to use the
      new statistical framework described here to estimate the dietary responses of
      grizzlies to declines in whitebark pine seeds and other important food sources
      through time in the GYE (e.g., cutthroat trout), as such information could be
      useful in predicting how the population will adapt to future environmental
      change.

PMID- 28493930
TI  - Clinical laboratory reference values amongst children aged 4 weeks to 17 months
      in Kilifi, Kenya: A cross sectional observational study.
AB  - Reference intervals for clinical laboratory parameters are important for
      assessing eligibility, toxicity grading and management of adverse events in
      clinical trials. Nonetheless, haematological and biochemical parameters used for
      clinical trials in sub-Saharan Africa are typically derived from industrialized
      countries, or from WHO references that are not region-specific. We set out to
      establish community reference values for haematological and biochemical
      parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We
      conducted a cross sectional study nested within phase II and III trials of RTS, S
      malaria vaccine candidate. We analysed 10 haematological and 2 biochemical
      parameters from 1,070 and 423 community children without illness prior to
      experimental vaccine administration. Statistical analysis followed Clinical and
      Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and
      their respective 90% confidence intervals were determined using non-parametric
      methods. Findings were compared with published ranges from Tanzania, Europe and
      The United States. We determined the reference ranges within the following age
      partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months
      to 17 months for the haematological parameters; and 4 weeks to 17 months for the
      biochemical parameters. There were no gender differences for all haematological
      and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference
      ranges in infants largely overlapped with those from United States or Europe,
      except for the lower limit for Hb, Hct and platelets (lower); and upper limit for
      platelets (higher) and haematocrit(lower). Community norms for common
      haematological and biochemical parameters differ from developed countries. This
      reaffirms the need in clinical trials for locally derived reference values to
      detect deviation from what is usual in typical children in low and middle income
      countries.

PMID- 28493931
TI  - Asymptomatic carotid artery stenosis and retinal nerve fiber layer thickness. A
      community-based, observational study.
AB  - PURPOSE: To examine whether an abnormally thin retinal nerve fiber layer (RNFL)
      is associated with cerebrovascular insufficiency. DESIGN: Community-based study.
      METHODS: The Asymptomatic Polyvascular Abnormalities in Community Study included
      Chinese aged 40+ years and without histories of cerebrovascular incidents or
      coronary heart disease. Using transcranial Doppler and carotid duplex ultrasound
      examination, we assessed presence and degree of an intracranial arterial stenosis
      (ICAS) and extracranial carotid arterial stenosis (ECAS) and we measured the RNFL
      thickness by spectral-domain optical coherence tomography. RESULTS: The study
      included 3,376 participants with a mean age of 54.3+/-10.3 years. Thinner RNFL
      was significantly correlated with a higher prevalence of ECAS (P = 0.035;
      standardized regression coefficient beta:-0.04; non-standardized regression
      coefficient B:-0.99; 95% confidence intervals(CI):-1.90,-0.07), after adjusting
      for age (P<0.001;beta:-0.25;B:-0.26;95%CI:-0.30,-0.22), gender (P = 0.001;beta:
      0.07;B:-1.36;95%CI:-2.14,-0.58) and blood concentration of low-density
      lipoproteins (P = 0.03;beta:0.04;B:0.52;95%CI:0.05,0.98). In a reverse manner,
      prevalence of ECAS was associated with a thinner RNFL thickness (P = 0.007; odds
      ratio (OR):0.99; 95%CI:0.98,0.99) after adjusting for older age
      (P<0.001;OR:1.06;95%CI:10.05,10.7), higher prevalence of ICAS (P =
      0.01;OR:1.34;95%CI:1.07,1.69) and higher prevalence of carotid artery plaques
      (P<0.001;OR:9.18;95%CI:6.93,12.2), and higher blood concentration of total
      cholesterol (P = 0.03;OR:1.12;95%CI:1.01,1.23). In univariate analysis, an
      increasing degree of ECAS was significantly correlated with a thinner RNFL.
      CONCLUSIONS: Higher prevalence and degree of ECAS were correlated with thinner
      RNFL and vice versa. Patients with abnormally thin RNFL without ocular disease
      may undergo carotid artery examination to detect asymptomatic carotid artery
      stenosis. Examination of the RNFL is useful for the diagnosis of cerebrovascular
      disease.

PMID- 28493932
TI  - Safety and tolerability of high-dose ulinastatin after 2-hour intravenous
      infusion in adult healthy Chinese volunteers: A randomized, double-blind, placebo
      controlled, ascending-dose study.
AB  - Ulinastatin, is a broad-spectrum protease inhibitor purified from human urine,
      inhibits endogenous proteases such as trypsin, alpha-chymotrypsin, hyaluronidase,
      and plasmin. It is widely being used at increasingly higher doses for the
      treatment of acute or chronic pancreatitis, severe infection, and acute organ
      failure. We aimed to evaluate the safety and tolerability of high-dose
      ulinastatin in healthy volunteers in our single center, randomized, double-blind,
      placebo-controlled, single-dose escalation study. Fifty-one healthy Chinese
      subjects were enrolled in 9 dose cohorts (3*105 U, 6*105 U, 12*105 U, 20*105 U,
      30*105 U, 45*105 U, 60*105 U, 70*105 U, or 80*105 U of ulinastatin) and
      randomized to UTI or matching placebo (n = 1). Each dose cohort was composed of 3
      7 subjects. All subjects were required to have 2 h of intravenous infusion.
      Safety and tolerability were assessed throughout the study via monitoring of
      vital signs, physical examinations, clinical laboratory tests, 12-lead
      electrocardiograms, and interviews with the subjects about adverse events. Fifty
      one subjects (35 men and 16 women) completed the study. A total of 13 AEs were
      reported by 10 subjects: 11 adverse events in the ulinastatin groups and 2
      adverse events in the placebo group. Twelve of the adverse events were possibly
      related to the study drug. The most common drug-related adverse events included
      dizziness, pain at injection site, and a decrease in white blood cell count. All
      adverse events were of mild severity; none were serious. In conclusion, 2 hours
      of intravenous infusion of ulinastatin (3*105 to 80*105 U) was well tolerated by
      healthy Chinese subjects.

PMID- 28493933
TI  - Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to
      lumretuzumab and pertuzumab in ER+ breast cancer.
AB  - Bidirectional cross talk between members of the human epidermal growth factor
      family of receptors (HER) and the estrogen receptor (ER) is believed to underlie
      resistance mechanisms that develop in response to treatment with anti-HER agents
      and endocrine therapy. We investigated the interaction between HER2, HER3 and the
      ER in vitro using human embryonic kidney cells transfected with human HER2, HER3,
      and ERalpha. We also investigated the additive efficacy of combination regimens
      consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine
      (fulvestrant) therapy in vivo. Our data show that both HER2 and HER3 can directly
      complex with the ER and can mediate phosphorylation of the ER. Phosphorylation of
      the ER was only observed in cells that expressed both HER2 and ERalpha or in
      heregulin-stimulated cells that expressed both HER3 and ERalpha. Using a mouse
      xenograft model of ER+/HER2-low (HER2 immunohistochemistry 1+ or 2+ without gene
      amplification) human breast cancer we show that the combination of lumretuzumab
      and pertuzumab is highly efficacious and induces long-lasting tumor regression in
      vivo and adding endocrine therapy (fulvestrant) to this combination further
      improved efficacy. In addition, a prolonged clinical response was observed with
      the combination of lumretuzumab and pertuzumab in a patient with ER+/HER2-low
      breast cancer who had failed endocrine therapy. These preclinical data confirm
      that direct cross talk exists between HER2/HER3 and ER which may explain the
      resistance mechanisms to endocrine therapy and monoclonal antibodies that target
      HER2 and HER3. Our data also indicate that the triplet of anti-HER2, anti-HER3,
      and endocrine therapy might be an efficacious combination for treating patients
      with ER+/HER2-low breast cancer, which is an area of significant unmet medical
      need.

PMID- 28493934
TI  - Taking stock of the social determinants of health: A scoping review.
AB  - BACKGROUND: In recent decades, the social determinants of health (SDOH) has
      gained increasing prominence as a foundational concept for population and public
      health in academic literature and policy documents, internationally. However,
      alongside its widespread dissemination, and in light of multiple conceptual
      models, lists, and frameworks, some dilution and confusion is apparent. This
      scoping review represents an attempt to take stock of SDOH literature in the
      context of contemporary population and public health. METHODS: We conducted a
      scoping review to synthesize and map SDOH literature, informed by the methods of
      Arksey and O'Malley (2005). We searched 5 academic and 3 grey literature
      databases for "social determinants of health" and "population health" or "public
      health" or "health promotion," published 2004-2014. We also conducted a search on
      "inequity" or "inequality" or "disparity" or "social gradient" and "Canad*" to
      ensure that we captured articles where this language was used to discuss the
      SDOH. We included articles that discussed SDOH in depth, either explicitly or in
      implicit but nuanced ways. We hand-searched reference lists to further identify
      relevant articles. FINDINGS: Our synthesis of 108 articles showed wide variation
      by study setting, target audience, and geographic scope, with most articles
      published in an academic setting, by Canadian authors, for policy-maker
      audiences. SDOH were communicated by authors as a list, model, or story; each
      with strengths and weaknesses. Thematic analysis identified one theme: health
      equity as an overarching and binding concept to the SDOH. Health equity was
      understood in different ways with implications for action on the SDOH.
      CONCLUSIONS: Among the vast SDOH literature, there is a need to identify and
      clearly articulate the essence and implications of the SDOH concept. We recommend
      that authors be intentional in their efforts to present and discuss SDOH to
      ensure that they speak to its foundational concept of health equity.

PMID- 28493935
TI  - Reproductive effort affects oxidative status and stress in an Antarctic penguin
      species: An experimental study.
AB  - The oxidative cost of reproduction has been a matter of debate in recent years
      presumably because of the lack of proper experimental studies. Based on the
      hypothesis that different brood sizes produce differential reproductive costs, an
      experimental manipulation during breeding of Adelie penguins was conducted at
      Hope Bay, Antarctica, to study oxidative status and stress. We predict that a
      lower reproductive effort should be positively related to low oxidative and
      physiological stress. We randomly assigned nests with two chicks to a control
      reproductive effort group (CRE), and by removing one chick from some nests with
      two chicks, formed a second, low reproductive effort group (LRE). We examined how
      oxidative status in blood plasma (reactive oxygen metabolites, ROMs, and total
      antioxidant capacity, OXY) and stress (heterophil/lymphocyte ratio, H/L)
      responded to a lower production of offspring total biomass. Our nest manipulation
      showed significant differences in offspring total biomass, which was lower in the
      LRE group. As predicted, the LRE group had higher antioxidant capacity than
      individuals in the CRE group. We have also found, although marginally
      significant, interactions between sex and treatment in the three variables
      analysed. Females had higher OXY, lower ROMs and lower H/L ratio when rearing one
      chick, whereas males did so when rearing two except for OXY which was high
      regardless of treatment. Moreover, there was a significant negative correlation
      between the H/L ratio and OXY in females. Finally, we have found a negative and
      significant relationship between the duration of the experiment and OXY and ROMs
      and positive with H/L ratio which suggests that indeed breeding penguins are
      paying an effort in physiological terms in relation to the duration of the chick
      rearing. In conclusion, a reduction of the reproductive effort decreased
      oxidative stress in this long-lived bird meaning that a link exists between
      breeding effort and oxidative stress. However, our findings suggest different sex
      strategies which results in opposite physiological responses presumably depending
      on different life-history strategies in males and females.

PMID- 28493936
TI  - Serum folate concentration and the incidence of lung cancer.
AB  - BACKGROUND: Lung cancer is a leading cause of cancer-related mortality globally.
      Folate helps to maintain DNA integrity and to regulate gene expression. Serum
      folate levels may affect the risk of several cancers, including lung cancer. In
      this study we evaluated the association between serum folate concentration and
      variations in genes involved in folate metabolism with lung cancer incidence in
      Poland. METHODS: The study included 366 lung cancer patients and 366 control
      subjects. We measured serum folate concentration and genotyped six variants in
      MTHFR, MTR and MTRR genes. The odds ratios of being diagnosed with lung cancer
      were calculated using conditional univariable and multivariable logistic
      regression with respect to folate level and genotypes. RESULTS: The mean serum
      folate level was lower in lung cancer cases than in control group (20.07 nmol/l
      vs. 22.52 nmol/l, p = 0.002). The odds ratio for lung cancer declined with
      increasing serum content of the folate. The folate concentration of >25.71 nmol/l
      (IVth quartile) in comparison to <15.92 nmol/l (Ist quartile) was associated with
      an odds ratio of 0.61 (95%CI 0.40-0.95, p = 0.03). The analysis of variations in
      MTHFR, MTR and MTRR genes did not reveal any significant difference between lung
      cancer cases and controls in univariable and multivariable analyses. CONCLUSION:
      In this case-control study, lower serum folate concentrations were associated
      with a higher risk of lung cancer diagnosis. Although previous findings have been
      somewhat mixed, our results add to the evidence that circulating folate levels
      may be an indicator of lung cancer risk.

PMID- 28493937
TI  - Action of tyrosinase on alpha and beta-arbutin: A kinetic study.
AB  - The known derivatives from hydroquinone, alpha and beta-arbutin, are used as
      depigmenting agents. In this work, we demonstrate that the oxy form of tyrosinase
      (oxytyrosinase) hydroxylates alpha and beta-arbutin in ortho position of the
      phenolic hydroxyl group, giving rise to a complex formed by met-tyrosinase with
      the hydroxylated alpha or beta-arbutin. This complex could evolve in two ways: by
      oxidizing the originated o-diphenol to o-quinone and deoxy-tyrosinase, or by
      delivering the o-diphenol and met-tyrosinase to the medium, which would produce
      the self-activation of the system. Note that the quinones generated in both cases
      are unstable, so the catalysis cannot be studied quantitatively. However, if 3
      methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is used, the o-quinone
      is attacked, so that it becomes an adduct, which can be oxidized by another
      molecule of o-quinone, generating o-diphenol in the medium. In this way, the
      system reaches the steady state and originates a chromophore, which, in turn, has
      a high absorptivity in the visible spectrum. This reaction allowed us to
      characterize alpha and beta-arbutin kinetically as substrates of tyrosinase for
      the first time, obtaining a Michaelis constant values of 6.5 +/- 0.58 mM and 3 +/
      0.19 mM, respectively. The data agree with those from docking studies that
      showed that the enzyme has a higher affinity for beta-arbutin. Moreover, the
      catalytic constants obtained by the kinetic studies (catalytic constant = 4.43 +/
      0.33 s-1 and 3.7 +/- 0.29 s-1 for alpha and beta-arbutin respectively) agree
      with our forecast based on 13 C NMR considerations. This kinetic characterization
      of alpha and beta-arbutin as substrates of tyrosinase should be taken into
      account to explain possible adverse effects of these compounds.

PMID- 28493938
TI  - Sleep spindle detection based on non-experts: A validation study.
AB  - Accurate and efficient detection of sleep spindles is a methodological challenge.
      The present study describes a method of using non-experts for manual detection of
      sleep spindles. We recruited five experts and 168 non-experts to manually
      identify spindles in stage N2 and stage N3 sleep data using a MATLAB interface.
      Scorers classified each spindle into definite and indefinite spindle (with
      weights of 1 and 0.5, respectively). First, a method of optimizing the thresholds
      of the expert/non-expert group consensus according to the results of experts and
      non-experts themselves is described. Using this method, we established expert and
      non-expert group standards from expert and non-expert scorers, respectively, and
      evaluated the performance of the non-expert group standards by compared with the
      expert group standard (termed EGS). The results indicated that the highest
      performance was the non-expert group standard when definite spindles were only
      considered (termed nEGS-1; F1 score = 0.78 for N2; 0.68 for N3). Second, four
      automatic spindle detection methods were compared with the EGS. We found that the
      performance of nEGS-1 versus EGS was higher than that of the four automated
      methods. Our results also showed positive correlation between the mean F1 score
      of individual expert in EGS and the F1 score of nEGS-1 versus EGS across 30
      segments of stage N2 data (r = 0.61, P < 0.001). Further, we found that six and
      nine non-experts were needed to manually identify spindles in stages N2 and N3,
      respectively, while maintaining acceptable performance of nEGS-1 versus EGS (F1
      score = 0.79 for N2; 0.64 for N3). In conclusion, this study establishes a
      detailed process for detection of sleep spindles by non-experts in a
      crowdsourcing scheme.

PMID- 28493939
TI  - Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell
      activation and Klebsiella pneumonia liver translocation.
AB  - Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess
      in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The
      effect and mechanism of diabetes on KP liver abscess was examined in
      streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP
      translocation to liver and plasma alaine transaminase levels were increased and
      liver clearance of KP was decreased in DM mice. Diabetic mice exhibited
      overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas
      growth in intestine, increased intestinal iNOS protein and nitrite levels in
      portal vein, and increased IL-1beta and TNF-alpha expression of Kupffer cells.
      Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation
      reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP
      translocation to liver. L-NAME treatment decreased intestinal iNOS protein
      expression as well as Kupffer cell activation and increased liver clearance of KP
      in DM mice. Dead E.coli (2*108 CFU/ml) feeding for one week induced iNOS and TLR4
      expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL
      1beta and TNF-alpha expression of Kupffer cells in GF mice but not in GF TLR4-/-
      mice. In conclusion, balance of intestinal microflora is important for preventing
      intestinal iNOS expression, Kupffer cell activation, and KP liver translocation
      in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L.
      salivarius decreases diabetes-induced intestinal iNOS expression and KP liver
      translocation. Diabetes induces Kupffer cell activation and KP liver
      translocation through enteric dysbiosis and nitric oxide production.

PMID- 28493940
TI  - Monte Carlo simulation for scanning technique with scattering foil free electron
      beam: A proof of concept study.
AB  - This study investigated the potential of a newly proposed scattering foil free
      (SFF) electron beam scanning technique for the treatment of skin cancer on the
      irregular patient surfaces using Monte Carlo (MC) simulation. After benchmarking
      of the MC simulations, we removed the scattering foil to generate SFF electron
      beams. Cylindrical and spherical phantoms with 1 cm boluses were generated and
      the target volume was defined from the surface to 5 mm depth. The SFF scanning
      technique with 6 MeV electrons was simulated using those phantoms. For
      comparison, volumetric modulated arc therapy (VMAT) plans were also generated
      with two full arcs and 6 MV photon beams. When the scanning resolution resulted
      in a larger separation between beams than the field size, the plan qualities were
      worsened. In the cylindrical phantom with a radius of 10 cm, the conformity
      indices, homogeneity indices and body mean doses of the SFF plans (scanning
      resolution = 1 degrees ) vs. VMAT plans were 1.04 vs. 1.54, 1.10 vs. 1.12 and 5
      Gy vs. 14 Gy, respectively. Those of the spherical phantom were 1.04 vs. 1.83,
      1.08 vs. 1.09 and 7 Gy vs. 26 Gy, respectively. The proposed SFF plans showed
      superior dose distributions compared to the VMAT plans.

PMID- 28493941
TI  - Influence of three lighting regimes during ten weeks growth phase on laying
      performance, plasma levels- and tissue specific gene expression- of reproductive
      hormones in Pengxian yellow pullets.
AB  - The study was conducted to optimize lighting schedule for pre-pubertal (12 to 22
      weeks) Chinese native breed Pengxian yellow pullet. A total of 414 healthy
      pullets (10 weeks), with similar body weight were randomly distributed into three
      groups (n = 138) and housed in individual cages for up to 12 weeks of age in
      light controlled rooms and provided normal lighting schedule (10L:14D). At 12 to
      18 weeks of age, pullets were housed in three rooms, having varying lighting
      schedule viz. G1 (8L: 16D), G2 (10L:14D), or G3 (12L:12D). From 19th week onwards
      lighting schedule was gradually increased every week in incremental manner till
      all groups started receiving 16L:8D lighting schedule. The age at first egg,
      weight of first egg laid, percent peak hen day egg production, concentration of
      plasma luteinizing and follicle-stimulating hormones and expression of genes
      regulating synthesis or/and secretion of hypothalamic gonadotropin-releasing
      hormone-I (GnRH-I), and pituitary LH-beta and FSH-beta were studied during
      experimental period (12 to 43 weeks of age) of this study. The result indicated
      that pullets of long day length (G3) group had higher plasma levels of FSH and LH
      and also better mRNA expression that regulates synthesis or/and secretion of GnRH
      I, FSH-beta, and LH-beta before egg laying. The age at first egg (151.3 days) in
      pullets of G3 group receiving longer lighting hours (12L:12D) was 8.8 days less
      (P<0.05) compared to pullets of G1 group, while it was 6.9 days less (P>0.05)
      compared to G2. However, significantly higher (P<0.05) plasma levels of LH and
      FSH in pullets of G1 as compared to pullets belonging to G3 group corresponded
      with the higher (P<0.05) cumulative egg production during the experimental
      period, while these attributes in G2 group didn't differ from either G1 or G3
      groups. Pullets of G1 group had significantly higher levels (P<0.05) of GnRH-I,
      FSH-beta, and LH-beta mRNA abundances at 43 weeks of age than other two groups
      and this corresponded with the percent (hen day) peak egg production (75.38%) in
      pullets in this G1 group that was attained at 32 weeks of age, while the peak
      production of 71.24% was attained at 30 weeks of age in G3 group. There was no
      effect of lighting schedule on body weight of pullets, recorded during
      experimental period, at all occasions; belonging to three groups (G1,G2 and G3)
      and receiving varying hours of photo-stimulation (P>0.05). It was inferred that
      the optimum lighting schedule for Chinese native breed Pengxian yellow pullets
      during 10 weeks of pre-pubertal growth period is short hours of photo-stimulation
      (i.e 8L:16D).

PMID- 28493943
TI  - Open lung approach versus standard protective strategies: Effects on driving
      pressure and ventilatory efficiency during anesthesia - A pilot, randomized
      controlled trial.
AB  - BACKGROUND: Low tidal volume (VT) during anesthesia minimizes lung injury but may
      be associated to a decrease in functional lung volume impairing lung mechanics
      and efficiency. Lung recruitment (RM) can restore lung volume but this may
      critically depend on the post-RM selected PEEP. This study was a randomized, two
      parallel arm, open study whose primary outcome was to compare the effects on
      driving pressure of adding a RM to low-VT ventilation, with or without an
      individualized post-RM PEEP in patients without known previous lung disease
      during anesthesia. METHODS: Consecutive patients scheduled for major abdominal
      surgery were submitted to low-VT ventilation (6 ml.kg-1) and standard PEEP of 5
      cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM
      and were randomly allocated to either continue with the same PEEP (RM-5 group, n
      = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA
      group, n = 18) defined as the level resulting in maximal Cdyn during a
      decremental PEEP trial. We compared the effects on driving pressure and lung
      efficiency measured by volumetric capnography. RESULTS: OL-PEEP was found at 8+/
      2 cmH2O. 36 patients were included in the final analysis. When compared with pre
      RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving
      pressure when compared to pre-RM. These parameters did not improve in the RM-5.
      The trend of the DP was significantly different between the OLA and RM-5 groups
      (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p
      = 0.035). CONCLUSIONS: Lung recruitment applied during low-VT ventilation
      improves driving pressure and lung efficiency only when applied as an open-lung
      strategy with an individualized PEEP in patients without lung diseases undergoing
      major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02798133.

PMID- 28493942
TI  - Amplifying recombination genome-wide and reshaping crossover landscapes in
      Brassicas.
AB  - Meiotic recombination by crossovers (COs) is tightly regulated, limiting its key
      role in producing genetic diversity. However, while COs are usually restricted in
      number and not homogenously distributed along chromosomes, we show here how to
      disrupt these rules in Brassica species by using allotriploid hybrids (AAC, 2n =
      3x = 29), resulting from the cross between the allotetraploid rapeseed (B. napus,
      AACC, 2n = 4x = 38) and one of its diploid progenitors (B. rapa, AA, 2n = 2x =
      20). We produced mapping populations from different genotypes of both diploid AA
      and triploid AAC hybrids, used as female and/or as male. Each population revealed
      nearly 3,000 COs that we studied with SNP markers well distributed along the A
      genome (on average 1 SNP per 1.25 Mbp). Compared to the case of diploids,
      allotriploid hybrids showed 1.7 to 3.4 times more overall COs depending on the
      sex of meiosis and the genetic background. Most surprisingly, we found that such
      a rise was always associated with (i) dramatic changes in the shape of
      recombination landscapes and (ii) a strong decrease of CO interference. Hybrids
      carrying an additional C genome exhibited COs all along the A chromosomes, even
      in the vicinity of centromeres that are deprived of COs in diploids as well as in
      most studied species. Moreover, in male allotriploid hybrids we found that Class
      I COs are mostly responsible for the changes of CO rates, landscapes and
      interference. These results offer the opportunity for geneticists and plant
      breeders to dramatically enhance the generation of diversity in Brassica species
      by disrupting the linkage drag coming from limits on number and distribution of
      COs.

PMID- 28493944
TI  - A decade of viral mutations and associated drug resistance in a population of HIV
      1+ Puerto Ricans: 2002-2011.
AB  - Puerto Rico has one of the highest rates of HIV/AIDS seen for any US state or
      territory, and antiretroviral therapy has been a mainstay of efforts to mitigate
      the HIV/AIDS public health burden on the island. We studied the evolutionary
      dynamics of HIV-1 mutation and antiretroviral drug resistance in Puerto Rico by
      monitoring the population frequency of resistance-associated mutations from 2002
      to 2011. Whole blood samples from 4,475 patients were analyzed using the TRUGENE
      HIV-1 Genotyping Kit and OpenGene DNA Sequencing System in the Immunoretrovirus
      Research Laboratory at Universidad Central del Caribe. Results show that 64.0% of
      female and 62.9% of male patients had HIV-1 mutations that confer resistance to
      at least one antiretroviral medication. L63P and M184V were the dominant
      mutations observed for the protease (PRO) and reverse transcriptase (RT) encoding
      genes, respectively. Specific resistance mutations, along with their associated
      drug resistance profiles, can be seen to form temporal clusters that reveal a
      steadily changing landscape of resistance trends over time. Both women and men
      showed resistance mutations for an average of 4.8 drugs over the 10-year period,
      further underscoring the strong selective pressure exerted by antiretrovirals
      along with the rapid adaptive response of HIV. Nevertheless, both female and male
      patients showed a precipitous decrease for overall drug resistance, and for PRO
      mutations in particular, over the entire course of the study, with the most rapid
      decrease in frequency seen after 2006. The reduced HIV-1 mutation and drug
      resistance trends that we observed are consistent with previous reports from
      multi-year studies conducted around the world. Reduced resistance can be
      attributed to the use of more efficacious antiretroviral drug therapy, including
      the introduction of multi-drug combination therapies, which limited the ability
      of the virus to mount rapid adaptive responses to antiretroviral selection
      pressure.

PMID- 28493945
TI  - Ebola virus RNA detection on fomites in close proximity to confirmed Ebola
      patients; N'Zerekore, Guinea, 2015.
AB  - OBJECTIVE: Health care workers (HCWs) in contact with patients with Ebola virus
      disease (EVD) are exposed to a risk of viral contamination. Fomites contaminated
      with the patient's blood or body fluids represents this risk. Our study aims to
      detect Ebola virus (EBOV) RNA within the high- and low-risk areas of an Ebola
      treatment unit (ETU) located in inland Guinea during the 2014-2015 West African
      Ebola epidemics. For samples from patients' immediate vicinity, we aim to seek an
      association between viral RNA detectability and level of plasma viral load of
      patients (intermediate to high, or very high). METHODS: Swabbing was performed on
      immediate vicinity of Ebola patients, on surfaces of an ETU, and on personal
      protective equipment (PPE) of HCWs after patient care and prior to doffing. All
      samples were assessed by quantitative reverse-transcribed PCR (RT-qPCR). RESULTS:
      32% (22/68) of swabs from high-risk areas were tested positive for EBOV RNA,
      including 42% (18/43) from patients' immediate vicinity, and 16% (4/25) from HCWs
      PPE. None of specimens from low-risk areas were tested positive (0/19). Swabs
      were much more often viral RNA positive in the vicinity of patients with a very
      high plasma viral load (OR 6.7, 95% CI [1.7-23.4]). CONCLUSION: Our findings show
      the persistence of EBOV RNA in the environment of Ebola patients and of HCWs, in
      a Guinean ETU, despite strict infection prevention and control measures. This
      detection raises the possibility that patients' environment could be a potential
      source of contamination with the virus.

PMID- 28493946
TI  - Functional decline in nursing home residents: A prognostic study.
AB  - AIM: To verify the probability of maintaining functional capacity in basic
      activities of daily living and identify the prognostic factors of functional
      decline in institutionalized older adults. METHODS: A longitudinal study is
      presented herein, with 5 waves every 6 months, throughout 2 years (2013-2015),
      conducted with individuals >=60 years old in 10 nursing homes in the city of
      Natal-RN (Brazil). Functional capacity was assessed by the items 'eating',
      'personal hygiene', 'dressing', 'bathing', 'transferring', 'toileting' and
      'walking', through a 5-item Likert scale. Sociodemographic, institution-related
      and health-related variables were considered to establish the baseline. Time
      dependent variables included continence decline, cognitive decline, increase in
      the number of medication, and incidences of falls, hospitalizations and
      fractures. The actuarial method, the log-rank test and Cox's regression were
      applied as statistical methods. RESULTS: The cumulative probability of functional
      maintenance was 78.2% (CI 95%: 72.8-82.7%), 65.1% (CI 95%: 58.9-70.5%), 53.5% (CI
      95%: 47.2-59.5%) and 44.0% (CI 95%: 37.7-50.2%) at 6, 12, 18 and 24 months,
      respectively. Predicting factors for functional decline were: severe cognitive
      impairment (HR = 1.96; p = 0.001), continence decline (HR = 1.85; p = 0.002) and
      incidence of hospitalizations (HR = 1.62; p = 0.020), adjusted by the incidence
      of depression, age, education level, presence of chronic diseases and low weight.
      CONCLUSIONS: The cumulative probability of maintaining functional capacity in
      institutionalized older adults was only 44% at the 2-year follow-up. Prognostic
      factors for functional decline included severe cognitive impairment, continence
      decline and incidence of hospitalizations.

PMID- 28493948
TI  - Gender bias in clinical case reports: A cross-sectional study of the "big five"
      medical journals.
AB  - BACKGROUND: Gender bias in medical journals can affect the science and the
      benefit to patients. It has never been investigated in clinical case reports. The
      oversight is important because of the role clinical case reports play in
      hypothesis generation and medical education. We investigated contemporary gender
      bias in case reports for the highest ranked journals in general and internal
      medicine. METHODS: PubMed case reports data from 2011 to 2016 were extracted for
      the Annals of Internal Medicine, British Medical Journal, the Journal of the
      American Medical Association, The Lancet, and New England Journal of Medicine.
      The gender of the patients were identified and a text analysis of the Medical
      Subject Headings conducted. RESULTS: A total of 2,742 case reports were
      downloaded and 2,582 (95.6%) reports contributed to the final analysis. A pooled
      analysis showed a statistically significant gender bias against female case
      reports (0.45; 95%CI: 0.43-0.47). The Annals of Internal Medicine was the only
      journal with a point estimate (non significant) in the direction of a bias
      against male patients. The text analysis identified no substantive difference in
      the focus of the case reports and no obvious explanation for the bias.
      CONCLUSION: Gender bias, previously identified in clinical research and in
      clinical authorship, extends into the patients presented in clinical case
      reports. Whether it is driven by authors or editors is not clear, but it likely
      contributes to and supports an overall male bias of clinical medicine.

PMID- 28493947
TI  - Post-translational modifications of FDA-approved plasma biomarkers in
      glioblastoma samples.
AB  - Liquid chromatography-tandem mass spectrometry was used to analyze plasma
      proteins of volunteers (control) and patients with glioblastoma multiform (GBM).
      A database search was pre-set with a variable post-translational modification
      (PTM): phosphorylation, acetylation or ubiquitination. There were no significant
      differences between the control and the GBM groups regarding the number of
      protein identifications, sequence coverage or number of PTMs. However, in GBM
      plasma, we unambiguously observed a decreased fraction in post-translationally
      modified peptides identified with high quality. The disease-specific PTM patterns
      were extracted and mapped to the set of FDA-approved plasma protein markers.
      Decreases of 46% and 24% in the number of acetylated and ubiquitinated peptides,
      respectively, were observed in the GBM samples. Significance of capturing disease
      associated patterns of protein modifications was envisaged.

PMID- 28493949
TI  - Prediction of pancreatic fistula after pancreatoduodenectomy by preoperative
      dynamic CT and fecal elastase-1 levels.
AB  - OBJECTIVE: To validate preoperative dynamic CT and fecal elastase-1 level in
      predicting the development of pancreatic fistulae after pancreatoduodenectomy.
      MATERIALS AND METHODS: For 146 consecutive patients, CT attenuation values of the
      nontumorous pancreatic parenchyma were retrospectively measured on precontrast,
      arterial and equilibrium phase images for calculation of enhancement ratios. CT
      enhancement ratios and preoperative fecal elastase-1 levels were correlated with
      the development of pancreatic fistulae using independent t-test, logistic
      regression models, ROC analysis, Youden method and tree analysis. RESULTS: The
      mean value of enhancement ratio on equilibrium phase was significantly higher (p
      = 0.001) in the patients without pancreatic fistula (n = 107; 2.26+/-3.63) than
      in the patients with pancreatic fistula (n = 39; 1.04+/-0.51); in the logistic
      regression analyses, it was significant predictor for the development of
      pancreatic fistulae (odds ratio = 0.243, p = 0.002). The mean preoperative fecal
      elastase-1 levels were higher (odds ratio = 1.003, p = 0.034) in the pancreatic
      fistula patients than other patients, but there were no significant differences
      in the areas under the curve between the prediction values of CT enhancement
      ratios and fecal elastase-1 combined and those of CT enhancement ratios alone (P
      = 0.897, p = 0.917) on ROC curve analysis. Tree analysis revealed that the CT
      enhancement ratio was more powerful predictor of pancreatic fistula than fecal
      elastase-1 levels. CONCLUSION: The preoperative CT enhancement ratio of pancreas
      acquired at equilibrium phase regardless of combination with fecal elastase-1
      levels might be a useful predictor of the risk of developing a pancreatic fistula
      following pancreatoduodenectomy.

PMID- 28493950
TI  - SAS profile correlations reveal SAS hierarchical nature and information content.
AB  - In structural biology, Small-Angle Scattering experiments (SAS) are unique,
      because although they provide low resolution data, they can be performed in
      closer-to-native conditions than those arising in X-Ray crystallography. A number
      of questions on SAS, however, remain unsolved, particularly in the light of
      modelling ensembles of conformers in solution. In this article, we study the
      ensemble average and covariance of SAS profiles analytically. Using this ensemble
      covariance, we demonstrate the hierarchical nature of SAS profiles. Furthermore,
      we show that the information content is not uniform and reaches its maximum in
      the intermediate q range. The arguments are generalized using microsecond-scale
      molecular dynamics trajectories of the lysozyme and on an ensemble of the
      intrinsically disordered protein p15PAF. We show that for highly flexible
      systems, the SAS profile is a representation of the ensemble of conformers in
      solution, and not that of one conformer in particular.

PMID- 28493951
TI  - Properties of biochar derived from wood and high-nutrient biomasses with the aim
      of agronomic and environmental benefits.
AB  - Biochar production and use are part of the modern agenda to recycle wastes, and
      to retain nutrients, pollutants, and heavy metals in the soil and to offset some
      greenhouse gas emissions. Biochars from wood (eucalyptus sawdust, pine bark),
      sugarcane bagasse, and substances rich in nutrients (coffee husk, chicken manure)
      produced at 350, 450 and 750 degrees C were characterized to identify agronomic
      and environmental benefits, which may enhance soil quality. Biochars derived from
      wood and sugarcane have greater potential for improving C storage in tropical
      soils due to a higher aromatic character, high C concentration, low H/C ratio,
      and FTIR spectra features as compared to nutrient-rich biochars. The high ash
      content associated with alkaline chemical species such as KHCO3 and CaCO3,
      verified by XRD analysis, made chicken manure and coffee husk biochars potential
      liming agents for remediating acidic soils. High Ca and K contents in chicken
      manure and coffee husk biomass can significantly replace conventional sources of
      K (mostly imported in Brazil) and Ca, suggesting a high agronomic value for these
      biochars. High-ash biochars, such as chicken manure and coffee husk, produced at
      low-temperatures (350 and 450 degrees C) exhibited high CEC values, which can be
      considered as a potential applicable material to increase nutrient retention in
      soil. Therefore, the agronomic value of the biochars in this study is
      predominantly regulated by the nutrient richness of the biomass, but an increase
      in pyrolysis temperature to 750 degrees C can strongly decrease the adsorptive
      capacities of chicken manure and coffee husk biochars. A diagram of the agronomic
      potential and environmental benefits is presented, along with some guidelines to
      relate biochar properties with potential agronomic and environmental uses. Based
      on biochar properties, research needs are identified and directions for future
      trials are delineated.

PMID- 28493952
TI  - A mutation in the CACNA1C gene leads to early repolarization syndrome with
      incomplete penetrance: A Chinese family study.
AB  - BACKGROUND: Early repolarization syndrome (ERS) may be a near-Mendelian or an
      oligogenic disease; however, no direct evidence has been provided to support this
      theory. METHODS AND RESULTS: We described a large Chinese family with nocturnal
      sudden cardiac death induced by ERS in most of the young male adults. One
      missense mutation (p.Q1916R) was found in the major subunit of the L-type calcium
      channel gene CACNA1C by the direct sequencing of candidate genes. A concomitant
      gain-of-function variant in the sodium channel gene SCN5A (p.R1193Q) was found to
      rescue the phenotype of the female CACNA1C-Q1916R mutation carriers, which led to
      the incomplete penetrance. The functional studies, via the exogenous expression
      approach, revealed that the CACNA1C-Q1916R mutation led to a decreasing L-type
      calcium current and the protein expression defect. The decreased calcium current
      produced by the mutant channel was improved by isoproterenol but exacerbated by
      testosterone. The effects of CACNA1C-Q1916R mutation and testosterone on cellular
      electrophysiology were further confirmed by the human ventricular action
      potential simulation. CONCLUSIONS: Our results demonstrated that the loss-of
      function CACNA1C-Q1916R mutation contributed to ERS-related sudden cardiac death,
      and the phenotypic incomplete penetrance was modified by the SCN5A-R1193Q variant
      and sex. These findings suggest that phenotypes of ERS are modified by multiple
      genetic factors, which supports the theory that ERS may be an oligogenic disease.

PMID- 28493953
TI  - The association between vacA or cagA status and eradication outcome of
      Helicobacter pylori infection: A meta-analysis.
AB  - BACKGROUND: H. pylori virulence factors, especially vacA and cagA are important
      in gastroduodenal disease pathogenesis and affect cure rates. This meta-analysis
      aimed to clarify the association between vacA or cagA status and eradication
      outcome of H. pylori infection. METHODS: A literature search was performed using
      electronic databases to identify studies. Twenty-six prospective studies were
      determined eligible. Meta-analytical techniques were conducted to calculate
      eradication rates and pooled relative ratios (RR). RESULTS: The eradication rate
      was greater approximately 10% in vacA s1 compared with vacA s2 infected patients,
      and the pooled RR was 1.164 (95%CI: 1.040-1.303, P = 0.008). A significant
      association existed between vacA s1 and higher eradication rates in Europe (RR:
      1.203, 95%CI: 1.003-1.442, P = 0.046) and Asia (RR: 1.187, 95%CI: 1.028-1.371, P
      = 0.020), in triple therapy patients (RR: 1.175, 95%CI: 1.012-1.365, P = 0.035).
      Eradication rates were similar for vacA m1 and m2 genotypes (RR: 0.981, 95%CI:
      0.891-1.080, P = 0.690), whereas they were higher by approximately 8% in cagA
      positive compared with cagA-negative infected patients, with a pooled RR of 1.094
      (95%CI: 1.025-1.168, P = 0.007). A significant association existed between cagA
      positive and increased eradication rates in Europe (RR: 1.138, 95%CI: 1.000
      1.295, P = 0.049) and Asia (RR: 1.118, 95%CI: 1.051-1.190, P<0.001), in using PCR
      (RR: 1.232, 95%CI: 1.142-1.329, P<0.001) and protein chips (RR: 1.200, 95%CI:
      1.060-1.359, P = 0.004), in triple therapy patients (RR: 1.090, 95%CI: 1.006
      1.181, P = 0.034). CONCLUSIONS: Evidence indicates that infection with vacA s1,
      cagA-positive strains, but not vacA s2, cagA-negative, is more conducive to H.
      pylori eradication.

PMID- 28493954
TI  - A model for predicting Xanthomonas arboricola pv. pruni growth as a function of
      temperature.
AB  - A two-step modeling approach was used for predicting the effect of temperature on
      the growth of Xanthomonas arboricola pv. pruni, causal agent of bacterial spot
      disease of stone fruit. The in vitro growth of seven strains was monitored at
      temperatures from 5 to 35 degrees C with a Bioscreen C system, and a calibrating
      equation was generated for converting optical densities to viable counts. In
      primary modeling, Baranyi, Buchanan, and modified Gompertz equations were fitted
      to viable count growth curves over the entire temperature range. The modified
      Gompertz model showed the best fit to the data, and it was selected to estimate
      the bacterial growth parameters at each temperature. Secondary modeling of
      maximum specific growth rate as a function of temperature was performed by using
      the Ratkowsky model and its variations. The modified Ratkowsky model showed the
      best goodness of fit to maximum specific growth rate estimates, and it was
      validated successfully for the seven strains at four additional temperatures. The
      model generated in this work will be used for predicting temperature-based
      Xanthomonas arboricola pv. pruni growth rate and derived potential daily
      doublings, and included as the inoculum potential component of a bacterial spot
      of stone fruit disease forecaster.

PMID- 28493956
TI  - Socio-demographic predictors and average annual rates of caesarean section in
      Bangladesh between 2004 and 2014.
AB  - BACKGROUND: Globally the rates of caesarean section (CS) have steadily increased
      in recent decades. This rise is not fully accounted for by increases in clinical
      factors which indicate the need for CS. We investigated the socio-demographic
      predictors of CS and the average annual rates of CS in Bangladesh between 2004
      and 2014. METHODS: Data were derived from four waves of nationally representative
      Bangladesh Demographic and Health Survey (BDHS) conducted between 2004 and 2014.
      Rate of change analysis was used to calculate the average annual rate of increase
      in CS from 2004 to 2014, by socio-demographic categories. Multi-level logistic
      regression was used to identify the socio-demographic predictors of CS in a cross
      sectional analysis of the 2014 BDHS data. RESULT: CS rates increased from 3.5% in
      2004 to 23% in 2014. The average annual rate of increase in CS was higher among
      women of advanced maternal age (>=35 years), urban areas, and relatively high
      socio-economic status; with higher education, and who regularly accessed
      antenatal services. The multi-level logistic regression model indicated that
      lower (<=19) and advanced maternal age (>=35), urban location, relatively high
      socio-economic status, higher education, birth of few children (<=2), antenatal
      healthcare visits, overweight or obese were the key factors associated with
      increased utilization of CS. Underweight was a protective factor for CS.
      CONCLUSION: The use of CS has increased considerably in Bangladesh over the
      survey years. This rising trend and the risk of having CS vary significantly
      across regions and socio-economic status. Very high use of CS among women of
      relatively high socio-economic status and substantial urban-rural difference call
      for public awareness and practice guideline enforcement aimed at optimizing the
      use of CS.

PMID- 28493955
TI  - Molecular diversity analysis, drought related marker-traits association mapping
      and discovery of excellent alleles for 100-day old plants by EST-SSRs in cassava
      germplasms (Manihot esculenta Cranz).
AB  - Cassava is the third largest food crop of the world and has strong ability of
      drought tolerance. In order to evaluate the molecular diversity and to discover
      novel alleles for drought tolerance in cassava germplasms, we examined a total of
      107 abiotic stress related expressed sequence tags-simple sequence repeat (EST
      SSR) markers in 134 cassava genotypes coming from planting regions worldwide and
      performed drought related marker-traits association mapping. As results, we
      successfully amplified 98 of 107 markers in 97 polymorphic loci and 279 alleles,
      with 2.87 alleles per locus, gene diversity of 0.48 and polymorphic information
      content (PIC) of 0.41 on average. The genetic coefficient between every two lines
      was 0.37 on average, ranging from 0.21 to 0.82. According to our population
      structure analysis, these samples could be divided into three sub-populations
      showing obvious gene flow between them. We also performed water stress
      experiments using 100-day old cassava plants in two years and calculated the
      drought tolerance coefficients (DTCs) and used them as phenotypes for marker
      trait association mapping. We found that 53 markers were significantly associated
      with these drought-related traits, with a contribution rate for trait variation
      of 8.60% on average, ranging between 2.66 and 28.09%. Twenty-four of these 53
      associated genes showed differential transcription or protein levels which were
      confirmed by qRT-PCR under drought stress when compared to the control conditions
      in cassava. Twelve of twenty-four genes were the same differential expression
      patterns in omics data and results of qRT-PCR. Out of 33 marker-traits
      combinations on 24 loci, 34 were positive and 53 negative alleles according to
      their phenotypic effects and we also obtained the typical materials which carried
      these elite alleles. We also found 23 positive average allele effects while 10
      loci were negative according to their allele effects (AAEs). Our results on
      molecular diversity, locus association and differential expression under drought
      can prove beneficial to select excellent materials through marker assisted
      selection and for functional genes research in the future.

PMID- 28493958
TI  - Evolutionary transition towards permanent chloroplasts? - Division of
      kleptochloroplasts in starved cells of two species of Dinophysis (Dinophyceae).
AB  - Species within the marine toxic dinoflagellate genus Dinophysis are phagotrophic
      organisms that exploit chloroplasts (kleptochloroplasts) from other protists to
      perform photosynthesis. Dinophysis spp. acquire the kleptochloroplasts from the
      ciliate Mesodinium rubrum, which in turn acquires the chloroplasts from a unique
      clade of cryptophytes. Dinophysis spp. digest the prey nuclei and all other cell
      organelles upon ingestion (except the kleptochloroplasts) and they are therefore
      believed to constantly acquire new chloroplasts as the populations grow. Previous
      studies have, however, indicated that Dinophysis can keep the kleptochloroplasts
      active during long term starvation and are able to produce photosynthetic
      pigments when exposed to prey starvation. This indicates a considerable control
      over the kleptochloroplasts and the ability of Dinophysis to replicate its
      kleptochloroplasts was therefore re-investigated in detail in this study. The
      kleptochloroplasts of Dinophysis acuta and Dinophysis acuminata were analyzed
      using confocal microscopy and 3D bioimaging software during long term starvation
      experiments. The cell concentrations were monitored to confirm cell divisions and
      samples were withdrawn each time a doubling had occurred. The results show direct
      evidence of kleptochloroplastidic division and that the decreases in total
      kleptochloroplast volume, number of kleptochloroplasts and number of
      kleptochloroplast centers were not caused by dilution due to cell divisions. This
      is the first report of division of kleptochloroplasts in any protist without the
      associated prey nuclei. This indicates that Dinophysis spp. may be in a
      transitional phase towards possessing permanent chloroplasts, which thereby
      potentially makes it a key organism to understand the evolution of phototrophic
      protists.

PMID- 28493957
TI  - Ezrin interacts with S100A4 via both its N- and C-terminal domains.
AB  - Ezrin belongs to the ERM (ezrin, radixin, moesin) protein family that has a role
      in cell morphology changes, adhesion and migration as an organizer of the
      cortical cytoskeleton by linking actin filaments to the apical membrane of
      epithelial cells. It is highly expressed in a variety of human cancers and
      promotes metastasis. Members of the Ca2+-binding EF-hand containing S100 proteins
      have similar pathological properties; they are overexpressed in cancer cells and
      involved in metastatic processes. In this study, using tryptophan fluorescence
      and stopped-flow kinetics, we show that S100A4 binds to the N-terminal ERM domain
      (N-ERMAD) of ezrin with a micromolar affinity. The binding involves the F2 lobe
      of the N-ERMAD and follows an induced fit kinetic mechanism. Interestingly,
      S100A4 binds also to the unstructured C-terminal actin binding domain (C-ERMAD)
      with similar affinity. Using NMR spectroscopy, we characterized the complex of
      S100A4 with the C-ERMAD and demonstrate that no ternary complex is simultaneously
      formed with the two ezrin domains. Furthermore, we show that S100A4 co-localizes
      with ezrin in HEK-293T cells. However, S100A4 very weakly binds to full-length
      ezrin in vitro indicating that the interaction of S100A4 with ezrin requires
      other regulatory events such as protein phosphorylation and/or membrane binding,
      shifting the conformational equilibrium of ezrin towards the open state. As both
      proteins play an important role in promoting metastasis, the characterization of
      their interaction could shed more light on the molecular events contributing to
      this pathological process.

PMID- 28493959
TI  - Novel genetic locus at MHC region for esophageal squamous cell carcinoma in
      Chinese populations.
AB  - BACKGROUND: Our previous genome-wide association study (GWAS) identified three
      independent single nucleotide polymorphisms (SNPs) in human major
      histocompatibility complex (MHC) region showing association with esophageal
      squamous cell carcinoma (ESCC). In this study, we increased GWAS sample size on
      MHC region and performed validation in an independent ESCC cases and normal
      controls with aim to find additional loci at MHC region showing association with
      an increased risk to ESCC. METHODS: The 1,077 ESCC cases and 1,733 controls were
      genotyped using Illumina Human 610-Quad Bead Chip, and 451 cases and 374 controls
      were genotyped using Illumina Human 660W-Quad Bead Chip. After quality control,
      the selected SNPs were replicated by TaqMan genotyping assay on another 2,026
      ESCC cases and 2,384 normal controls. RESULTS: By excluding low quality SNPs in
      primary GWAS screening, we selected 2,533 SNPs in MHC region for association
      analysis, and identified 5 SNPs with p <10-4. Further validation analysis in an
      independent case-control cohort confirmed one of the 5 SNPs (rs911178) that
      showed significant association with ESCC. rs911178 (PGWAS = 6.125E-04, OR = 0.644
      and Preplication = 1.406E-22, OR = 0.489) was located at upstream of SCAND3.
      CONCLUSION: The rs911178 (SCAND3 gene) in MHC region is significantly associated
      with high risk of ESCC. This study not only reveal the potential role of MHC
      region for the pathogenesis of ESCC, but also provides important clues for the
      establishment of tools and methods for screening high risk population of ESCC.

PMID- 28493960
TI  - Diagnostic of students' misconceptions using the Biological Concepts Instrument
      (BCI): A method for conducting an educational needs assessment.
AB  - Concept inventories, constructed based on an analysis of students' thinking and
      their explanations of scientific situations, serve as diagnostics for identifying
      misconceptions and logical inconsistencies and provide data that can help direct
      curricular reforms. In the current project, we distributed the Biological
      Concepts Instrument (BCI) to 17-18-year-old students attending the highest track
      of the Swiss school system (Gymnasium). Students' performances on many questions
      related to evolution, genetics, molecular properties and functions were diverse.
      Important common misunderstandings were identified in the areas of evolutionary
      processes, molecular properties and an appreciation of stochastic processes in
      biological systems. Our observations provide further evidence that the BCI is
      efficient in identifying specific areas where targeted instruction is required.
      Based on these observations we have initiated changes at several levels to
      reconsider how biological systems are presented to university biology studies
      with the goal of improving student's foundational understanding.

PMID- 28493962
TI  - Genetic diversity and population structure of Chinese natural bermudagrass
      [Cynodon dactylon (L.) Pers.] germplasm based on SRAP markers.
AB  - Bermudagrass [Cynodon dactylon (L.) Pers.], an important turfgrass used in public
      parks, home lawns, golf courses and sports fields, is widely distributed in
      China. In the present study, sequence-related amplified polymorphism (SRAP)
      markers were used to assess genetic diversity and population structure among 157
      indigenous bermudagrass genotypes from 20 provinces in China. The application of
      26 SRAP primer pairs produced 340 bands, of which 328 (96.58%) were polymorphic.
      The polymorphic information content (PIC) ranged from 0.36 to 0.49 with a mean of
      0.44. Genetic distance coefficients among accessions ranged from 0.04 to 0.61,
      with an average of 0.32. The results of STRUCTURE analysis suggested that 157
      bermudagrass accessions can be grouped into three subpopulations. Moreover,
      according to clustering based on the unweighted pair-group method of arithmetic
      averages (UPGMA), accessions were divided into three major clusters. The UPGMA
      dendrogram revealed that accessions from identical or adjacent areas were
      generally, but not entirely, clustered into the same cluster. Comparison of the
      UPGMA dendrogram and the Bayesian STRUCTURE analysis showed general agreement
      between the population subdivisions and the genetic relationships among
      accessions. Principal coordinate analysis (PCoA) with SRAP markers revealed a
      similar grouping of accessions to the UPGMA dendrogram and STRUCTUE analysis.
      Analysis of molecular variance (AMOVA) indicated that 18% of total molecular
      variance was attributed to diversity among subpopulations, while 82% of variance
      was associated with differences within subpopulations. Our study represents the
      most comprehensive investigation of the genetic diversity and population
      structure of bermudagrass in China to date, and provides valuable information for
      the germplasm collection, genetic improvement, and systematic utilization of
      bermudagrass.

PMID- 28493961
TI  - Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the
      distal nephron from type 1 diabetic rats.
AB  - Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We
      evaluated the participation of aldosterone (ALD), and the effect of
      spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions
      of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal
      tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar
      rats by a single tail vein injection of streptozotocin (STZ), and SPL was
      administrated daily by gavage, from days 3-21. Twenty-one days after STZ
      injection the rats were sacrificed. In diabetic rats, the serum ALD levels were
      increased, and SPL-treatment did not have effect on these levels or in
      hyperglycemia, however, proteinuria decreased in SPL-treated diabetic rats.
      Glomerular damage, evaluated by nephrin and Wilm's tumor 1 (WT1) protein
      expressions, and proximal tubular damage, evaluated by kidney injury molecule 1
      (Kim-1) and heat shock protein 72 kDa (Hsp72) expressions, were ameliorated by
      SPL. Also, SPL prevented decrement in claudin-5 in glomeruli, and claudin-2 and
      occludin in proximal tubules by decreasing oxidative stress, evaluated by
      superoxide anion (O2?-) production, and oxidative stress markers. In distal
      tubules, SPL ameliorated increase in mRNA, protein expression, and
      phosphorylation in threonine residues of claudin-4 and -8, through a serum and
      glucocorticoid-induced kinase 1 (SGK1), and with-no-lysine kinase 4 (WNK4)
      signaling pathway. In conclusion, this is the first study that demonstrates that
      ALD modulates the expression of renal TJ proteins in diabetes, and that the
      blockade of its actions with SPL, may be a promising therapeutic strategy to
      prevent alterations of TJ proteins in diabetic nephropathy.

PMID- 28493963
TI  - Expression in Sf9 insect cells, purification and functional reconstitution of the
      human proton-coupled folate transporter (PCFT, SLC46A1).
AB  - The proton-coupled folate transporter (PCFT) provides an essential uptake route
      for the vitamin folic acid (B9) in mammals. In addition, it is currently of high
      interest for targeting chemotherapeutic agents to tumors due to the increased
      folic acid requirement of rapidly dividing tumor cells as well as the upregulated
      PCFT expression in several tumors. To understand its function, determination of
      its atomic structure and molecular mechanism of transport are essential goals
      that require large amounts of functional PCFT. Here, we present a high-level
      heterologous expression system for human PCFT using a recombinant baculovirus and
      Spodoptera frugiperda (Sf9) insect cells. We demonstrate folate transport
      functionality along the PCFT expression, isolation, and purification process.
      Importantly, purified PCFT transports folic acid after reconstitution. We thus
      succeeded in overcoming heterologous expression as a major bottleneck of PCFT
      research. The availability of an overexpression system for human PCFT provides
      the basis for future biochemical, biophysical and structural studies.

PMID- 28493964
TI  - Non-human primate orthologues of TMPRSS2 cleave and activate the influenza virus
      hemagglutinin.
AB  - The cellular serine protease TMPRSS2, a member of the type II transmembrane
      serine protease (TTSP) family, cleaves and activates the hemagglutinin of
      influenza A viruses (FLUAV) in cell culture and is essential for spread of
      diverse FLUAV in mice. Non-human primates (NHP), in particular rhesus and
      cynomolgus macaques, serve as animal models for influenza and experimental FLUAV
      infection of common marmosets has recently also been reported. However, it is
      currently unknown whether the NHP orthologues of human TMPRSS2 cleave and
      activate FLUAV hemagglutinin and contribute to viral spread in respiratory
      tissue. Here, we cloned and functionally analyzed the macaque and marmoset
      orthologues of human TMPRSS2. In addition, we analyzed the macaque orthologues of
      human TMPRSS4 and HAT, which also belong to the TTSP family. We found that all
      NHP orthologues of human TMPRSS2, TMPRSS4 and HAT cleave and activate HA upon
      directed expression and provide evidence that endogenous TMPRSS2 is expressed in
      the respiratory epithelium of rhesus macaques. Finally, we demonstrate that a
      serine protease inhibitor active against TMPRSS2 suppresses FLUAV spread in
      precision-cut lung slices of human, macaque and marmoset origin. These results
      indicate that FLUAV depends on serine protease activity for spread in diverse NHP
      and in humans. Moreover, our findings suggest that macaques and marmosets may
      serve as models to study FLUAV activation by TMPRSS2 in human patients.

PMID- 28493965
TI  - Assessing the greenhouse gas emissions of Brazilian soybean biodiesel production.
AB  - Soybean biodiesel (B100) has been playing an important role in Brazilian energy
      matrix towards the national bio-based economy. Greenhouse gas (GHG) emissions is
      the most widely used indicator for assessing the environmental sustainability of
      biodiesels and received particular attention among decision makers in business
      and politics, as well as consumers. Former studies have been mainly focused on
      the GHG emissions from the soybean cultivation, excluding other stages of the
      biodiesel production. Here, we present a holistic view of the total GHG emissions
      in four life cycle stages for soybean biodiesel. The aim of this study was to
      assess the GHG emissions of Brazilian soybean biodiesel production system with an
      integrated life cycle approach of four stages: agriculture, extraction,
      production and distribution. Allocation of mass and energy was applied and
      special attention was paid to the integrated and non-integrated industrial
      production chain. The results indicated that the largest source of GHG emissions,
      among four life cycle stages, is the agricultural stage (42-51%) for B100
      produced in integrated systems and the production stage (46-52%) for B100
      produced in non-integrated systems. Integration of industrial units resulted in
      significant reduction in life cycle GHG emissions. Without the consideration of
      LUC and assuming biogenic CO2 emissions is carbon neutral in our study, the
      calculated life cycle GHG emissions for domestic soybean biodiesel varied from
      23.1 to 25.8 gCO2eq. MJ-1 B100 and those for soybean biodiesel exported to EU
      ranged from 26.5 to 29.2 gCO2eq. MJ-1 B100, which represent reductions by 65% up
      to 72% (depending on the delivery route) of GHG emissions compared with the EU
      benchmark for diesel fuel. Our findings from a life cycle perspective contributed
      to identify the major GHG sources in Brazilian soybean biodiesel production
      system and they can be used to guide mitigation priority for policy and decision
      making. Projected scenarios in this study would be taken as references for
      accounting the environmental sustainability of soybean biodiesel within a
      domestic and global level.

PMID- 28493967
TI  - Water permeation through the internal water pathway in activated GPCR rhodopsin.
AB  - Rhodopsin is a light-driven G-protein-coupled receptor that mediates signal
      transduction in eyes. Internal water molecules mediate activation of the receptor
      in a rhodopsin cascade reaction and contribute to conformational stability of the
      receptor. However, it remains unclear how internal water molecules exchange
      between the bulk and protein inside, in particular through a putative solvent
      pore on the cytoplasmic. Using all-atom molecular dynamics simulations, we
      identified the solvent pore on cytoplasmic side in both the Meta II state and the
      Opsin. On the other hand, the solvent pore does not exist in the dark-adapted
      rhodopsin. We revealed two characteristic narrow regions located within the
      solvent pore in the Meta II state. The narrow regions distinguish bulk and the
      internal hydration sites, one of which is adjacent to the conserved structural
      motif "NPxxY". Water molecules in the solvent pore diffuse by pushing or
      sometimes jumping a preceding water molecule due to the geometry of the solvent
      pore. These findings revealed a total water flux between the bulk and the protein
      inside in the Meta II state, and suggested that these pathways provide water
      molecules to the crucial sites of the activated rhodopsin.

PMID- 28493966
TI  - Improving drug delivery strategies for lymphatic filariasis elimination in urban
      areas in Ghana.
AB  - The Global Program to Eliminate Lymphatic Filariasis (GPELF) advocates for the
      treatment of entire endemic communities, in order to achieve its elimination
      targets. LF is predominantly a rural disease, and achieving the required
      treatment coverage in these areas is much easier compared to urban areas that are
      more complex. In Ghana, parts of the Greater Accra Region with Accra as the
      capital city are also endemic for LF. Mass Drug Administration (MDA) in Accra
      started in 2006. However, after four years of treatment, the coverage has always
      been far below the 65% epidemiologic coverage for interrupting transmission. As
      such, there was a need to identify the reasons for poor treatment coverage and
      design specific strategies to improve the delivery of MDA. This study therefore
      set out to identify the opportunities and barriers for implementing MDA in urban
      settings, and to develop appropriate strategies for MDA in these settings. An
      experimental, exploratory study was undertaken in three districts in the Greater
      Accra region. The study identified various types of non-rural settings, the
      social structures, stakeholders and resources that could be employed for MDA.
      Qualitative assessment such as in-depth interviews (IDIs) and focus group
      discussions (FGDs) with community leaders, community members, health providers,
      NGOs and other stakeholders in the community was undertaken. The study was
      carried out in three phases: pre-intervention, intervention and post-intervention
      phases, to assess the profile of the urban areas and identify reasons for poor
      treatment coverage using both qualitative and quantitative research methods. The
      outcomes from the study revealed that, knowledge, attitudes and practices of
      community members to MDA improved slightly from the pre-intervention phase to the
      post-intervention phase, in the districts where the interventions were readily
      implemented by health workers. Many factors such as adequate leadership, funding,
      planning and community involvement, were identified as being important in
      improving implementation and coverage of MDA in the study districts. Implementing
      MDA in urban areas therefore needs to be given significant consideration and
      planning, if the required coverage rates are to be achieved. This paper, presents
      the recommendations and strategies for undertaking MDA in urban areas.

PMID- 28493968
TI  - The dead, hardened floral bracts of dispersal units of wild wheat function as
      storage for active hydrolases and in enhancing seedling vigor.
AB  - It is commonly assumed that the dead, hardened floral bracts of the dispersal
      unit of grasses have been evolved to protect seeds from predation and / or assist
      in fruit/caryopsis dispersal. While these structures have important agronomical
      and economical implications, their adaptive value has not been fully explored. We
      investigated the hypothesis that the maternally derived hardened floral bracts
      have been evolved not just as a means for caryopsis protection and dispersal, but
      also as storage for substances that might affect seed germination and seedling
      vigor. Dead glumes as well as lemmas and paleas of wild emmer wheat (Triticum
      turgidum var dicoccoides) were found to store and release upon hydration active
      hydrolases including nucleases and chitinases. High nuclease activity was
      released upon hydration from glumes derived from wild strains of wheat including
      Triticum urartu and wild emmer wheat, while very low nuclease activity was
      detected in glumes derived from domesticated, free-threshing wheat cultivars
      (e.g., durum wheat). Germination from the intact dispersal unit of wild emmer
      wheat was delayed, but post germination growth was better than those of separated
      caryopses. Most notable was a significant increase in lateral root production on
      seedlings germinated from the intact dispersal unit. Proteome analysis of wild
      emmer wheat glumes revealed many proteins stored and released upon hydration
      including S1-type nucleases, peptidases, antifungal hydrolases such as chitinases
      and beta-1,3-glucanase as well as pectin acetylesterase, a protein involved in
      cell wall degradation and remodeling. Also, reactive oxygen species (ROS)
      detoxifying enzymes such as superoxide dismutase and ascorbate peroxidase were
      overrepresented in dead glumes of wild emmer wheat. Thus our study highlighted
      previously unknown features of the dispersal unit in wild wheat in which the
      dead, hardened floral bracts enclosing the caryopsis store active hydrolases and
      nutritional elements and probably growth promoting substances that facilitate
      seed longevity and germination and increase seedling vigor.

PMID- 28493969
TI  - Activation and inactivation of Bacillus pumilus spores by kiloelectron volt X-ray
      irradiation.
AB  - In this study, we investigated the inactivation efficacy of endospore-forming
      bacteria, Bacillus pumilus, irradiated by low-energy X-rays of different beam
      qualities. The different low-energy X-rays studied had cut-off energies of 50,
      100 and 150 keV. Bacillus pumilus spores (in biological indicator strips) were
      irradiated at step doses between 6.5 to 390 Gy. The resulting bacteria
      populations were then quantified by a pour plate method. Results showed that X
      rays of lower energies were more effective in inactivating bacterial spores. In
      addition, an increment in bacterial population was observed at doses below 13Gy.
      We attributed this increase to a radiation-induced activation of bacterial
      spores. Four kinetic models were then evaluated for their prediction of bacterial
      spore behavior under irradiation. This included: (i) first-order kinetics model;
      (ii) Shull model; (iii) Sapru model; and (iv) probabilistic model. From R2 and
      AIC analyses, we noted that the probabilistic model performed the best, followed
      by the Sapru model. We highlighted that for simplicity in curve fitting the Sapru
      model should be used instead of the probabilistic model. A 12-log reduction in
      bacterial population (corresponding to a sterility assurance level of 10-6 as
      required in the sterilization of medical devices) was computed to be achievable
      at doses of 1000, 1600 and 2300 Gy for the three different X-ray cut-off energies
      respectively. These doses are an order in magnitude lesser than that required in
      gamma irradiation. This highlights the applicability of cheaper and safer table
      top X-ray sources for sterilization application.

PMID- 28493970
TI  - Elevation of secondary metabolites synthesis in Brassica campestris ssp.
      chinensis L. via exogenous inoculation of Piriformospora indica with appropriate
      fertilizer.
AB  - This work evaluated the impact of exogenous soil inoculation of beneficial fungal
      strain Piriformospora indica on phytochemical changes and the related genes
      expression of Chinese cabbage (Brassica campestris ssp. chinensis L.) by
      greenhouse pot experiments. High performance liquid chromatography (HPLC)
      affirmed that among the different combinations of fungal and organic fertilizer
      treatments, the phenolic acids and flavonoids were considerably enriched in
      organic fertilizer and fungi (OP) followed by organic fertilizer, biochar, fungi
      (OBP) treated plants. The antiradical activity was higher in OP (61.29%) followed
      by P (60%) and organic fertilizer (OF) (53.84%) inoculated plants which
      positively correlated with chlorophyll, carotenoids and flavonoids level
      (P<0.05). Furthermore, results showed that the exogenous application of P. indica
      significantly (P<0.05) enhanced plant growth, as well as stimulating the
      activation of chlorophyll, carotenoids and other antioxidant related pathways.
      The RT-qPCR analysis indicated that key FLS gene triggering the synthesis of
      kaemferol was up-regulated by the inoculation of P. indica. In conclusion, the
      results revealed that organic fertilizer and P. indica (OP) is the most
      appropriate combination for improving phytochemical and antiradical properties in
      Pakchoi.

PMID- 28493971
TI  - Nonsense variant in COL7A1 causes recessive dystrophic epidermolysis bullosa in
      Central Asian Shepherd dogs.
AB  - A rare hereditary mechanobullous disorder called epidermolysis bullosa (EB)
      causes blistering in the skin and the mucosal membranes. To date, nineteen EB
      related genes have been discovered in human and other species. We describe here a
      novel EB variant in dogs. Two newborn littermates of Central Asian Shepherd dogs
      with severe signs of skin blistering were brought to a veterinary clinic and
      euthanized due to poor prognosis. In post-mortem examination, the puppies were
      shown to have findings in the skin and the mucosal membranes characteristic of
      EB. A whole-genome sequencing of one of the affected puppies was performed to
      identify the genetic cause. The resequencing data were filtered under a recessive
      model against variants from 31 other dog genomes, revealing a homozygous case
      specific nonsense variant in one of the known EB-causing genes, COL7A1
      (c.4579C>T, p.R1527*). The variant results in a premature stop codon and likely
      absence of the functional protein in the basement membrane of the skin in the
      affected dogs. This was confirmed by immunohistochemistry using a COL7A1
      antibody. Additional screening of the variant indicated full penetrance and breed
      specificity at ~28% carrier frequency. In summary, this study reveals a novel
      COL7A1 variant causing recessive dystrophic EB and provides a genetic test for
      the eradication of the disease from the breed.

PMID- 28493973
TI  - Prevalence of Coxiella burnetii in cattle at South Korean national breeding stock
      farms.
AB  - This is the first study to evaluate the serologic and molecular prevalence of
      Coxiella burnetii in cattle at national breeding stock farms in South Korea.
      These government farms have well-organized biosecurity and management systems to
      prevent livestock diseases. Of the 736 cattle in this study, 77 tested positive
      for antibodies against C. burnetii antigens (10.5%, 95% CI: 8.3-12.7) and 11 were
      positive for a C. burnetti infection on PCR analysis (1.5%, 95% CI: 0.6-2.4).
      Since the 16S rRNA sequences of C. burnetii from all 11 PCR-positive samples were
      identical, three representative samples (C-CN-3 from the southern region, C-JJ-9
      from Jeju Island, and C-CB-37 from the central region) are described in this
      paper. These three sequences had 99.3-100% identity to those of C. burnetii
      deposited in GenBank. These sequences clustered with those from USA, Japan, and
      Greenland, underscoring the sequence similarity among C. burnetii isolates in
      these countries. Because C. burnetii was detected in cattle at well-managed
      national breeding stock farms, cattle at non-government operated farms may be
      more likely to be exposed to C. burnetii in South Korea. Thus, continuous
      surveillance and control strategies in animals and humans are required to prevent
      the transmission of C. burnetii to humans.

PMID- 28493972
TI  - Positive radionuclide imaging of miRNA expression using RILES and the human
      sodium iodide symporter as reporter gene is feasible and supports a protective
      role of miRNA-23a in response to muscular atrophy.
AB  - MicroRNAs (miRNAs) are key players in many biological processes and are
      considered as an emerging class of pharmacology drugs for diagnosis and therapy.
      However to fully exploit the therapeutic potential of miRNAs, it is becoming
      crucial to monitor their expression pattern using medical imaging modalities.
      Recently, we developed a method called RILES, for RNAi-Inducible Luciferase
      Expression System that relies on an engineered regulatable expression system to
      switch-ON the expression of the luciferase gene when a miRNA of interest is
      expressed in cells. Here we investigated whether replacing the luciferase
      reporter gene with the human sodium iodide symporter (hNIS) reporter gene will be
      also suited to monitor the expression of miRNAs in a clinical setting context. We
      provide evidence that radionuclide imaging of miRNA expression using hNIS is
      feasible although it is not as robust as when the luciferase reporter gene is
      used. However, under appropriate conditions, we monitored the expression of
      several miRNAs in cells, in the liver and in the tibialis anterior muscle of mice
      undergoing muscular atrophy. We demonstrated that radiotracer accumulation in
      transfected cells correlated with the induction of hNIS and with the expression
      of miRNAs detected by real time PCR. We established the kinetic of miRNA-23a
      expression in mice and demonstrated that this miRNA follows a biphasic expression
      pattern characterized by a loss of expression at a late time point of muscular
      atrophy. At autopsy, we found an opposite expression pattern between miRNA-23a
      and one of the main transcriptional target of this miRNA, APAF-1, and as
      downstream target, Caspase 9. Our results report the first positive monitoring of
      endogenously expressed miRNAs in a nuclear medicine imaging context and support
      the development of additional work to establish the potential therapeutic value
      of miRNA-23 to prevent the damaging effects of muscular atrophy.

PMID- 28493974
TI  - Serum alpha-1 Antitrypsin (AAT) antagonizes intrinsic apoptosis induction in
      neutrophils from patients with systemic inflammatory response syndrome.
AB  - Excessive neutrophil activation accompanied by delayed apoptotic cell death in
      inflammatory conditions causes progressive damage of cells and tissues, leading
      to life-threatening multiple organ dysfunction syndrome. Previous work suggested
      that circulating serum factors during inflammation are critically involved in the
      suppression of neutrophil cell death although the identity of these antiapoptotic
      mediators remained elusive. In this study, we identified the acute phase protein
      alpha-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced
      apoptosis in human neutrophils through a mechanism implicating caspases
      independent pathways. We show here that serum levels of AAT, potentially in part
      released by stimulated neutrophils, are markedly elevated in major trauma
      patients suffering from systemic inflammatory response syndrome (SIRS). Notably,
      AAT depletion from serum increased sensitivity of human neutrophils for STS
      induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis
      resistance by preventing PKC/Akt inactivation and subsequent proteasomal
      degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither
      MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered
      antiapoptotic pathways in neutrophils. In summary, these results establish a
      novel pivotal role of circulating AAT in mediating survival by antagonizing the
      proapoptotic action of the PKC inhibitor STS and should be considered for AAT
      augmentation therapies in future.

PMID- 28493976
TI  - "Passive victim - strong survivor"? Perceived meaning of labels applied to women
      who were raped.
AB  - Three experiments (total N = 464) were conducted in parallel with English- and
      German-speaking participants to examine the perceived meanings and effects of the
      labels "victim" versus "survivor" (and their German equivalents) when applied to
      a woman who was raped. In Study 1 (N = 179), participants read a rape vignette
      and then rated the meaning of the label it contained (either "victim" or
      "survivor") on a 15-item semantic differential. Independent of language and
      participant gender, "survivor" was perceived more positively overall (e.g., as
      strong, brave, active) than was "victim" (weak, passive, but also innocent). In
      Study 2 (N = 95), labels were varied within items assessing judgments of an
      acquaintance-rape case (e.g., "Does the victim [survivor] ... carry a certain
      responsibility for what happened?"), focusing on short-term outcomes. Significant
      interaction effects of label and participants' gender emerged on case-related
      judgments. Participants in both language samples judged "survivor" to be a less
      appropriate term than "victim". In Study 3 (N = 190), participants read a text in
      which a woman who had been raped labeled herself as either "victim" or
      "survivor", focusing on the coping with sexual violence. As in Study 2, German
      language participants showed no significant effects of the label on their case
      judgments but rejected the term "survivor" as inappropriate; English-language
      participants, by contrast, perceived the woman describing herself as "survivor"
      to be more psychologically stable and regarded the use of both labels as
      appropriate. Results are discussed in terms of their applied relevance for
      communicating about sexual violence.

PMID- 28493975
TI  - Molecular characterization, expression of chicken TBK1 gene and its effect on
      IRF3 signaling pathway.
AB  - TRAF family member-associated NF-kappaB activator (TANK)-binding kinase1 (TBK1)
      is a serine-threonine kinase at the crossroads of multiple interferon (IFN)
      inducing signaling pathways in innate immunity. The importance of TBK1 in
      antiviral immunity is well established in mammal models, but in chicken, the
      molecular characterization and potential function of TBK1 remain unclear. In the
      present study, the open-reading frame (ORF) of chicken TBK1 (chTBK1) was cloned
      and characterized. The sequencing results revealed that the chTBK1 ORF consists
      of 2190 base pairs (bp) encoding a deduced protein of 729 amino acid residues.
      Multiple sequence alignment analysis demonstrated chTBK1 similarity to other
      birds and mammals, which indicates that it is evolutionarily conserved.
      Quantitative real-time PCR (qRT-PCR) results showed that chTBK1 was ubiquitously
      expressed in chicken tissues and expression was especially high in immune
      tissues. In addition, the expression of chTBK1 was significantly up-regulated by
      infection with avian leukosis virus subgroup J (ALV-J) both in vivo and in
      chicken embryo fibroblasts (CEFs) challenged with ALV-J or stimulated with poly
      I:C in vitro. Consistent with the activation of chTBK1, the interferon regulatory
      factor 3 (IRF3) and IFNbeta gene in CEFs were also up-regulated after challenge
      with ALV-J or polyI:C. In contrast, the expression of IRF3 and IFNbeta in CEFs
      was significantly reduced by siRNA targeting the chTBK1 gene compared with a
      negative control (NC) during ALV-J infection or polyI:C transfection. In
      conclusion, our results demonstrated that chTBK1 may be an important
      immunoregulator for IRF3 and IFNbeta induction in response to viral stimulation
      in chicken.

PMID- 28493977
TI  - Robust multiple frequency multiple power localization schemes in the presence of
      multiple jamming attacks.
AB  - Localization of the wireless sensor network is a vital area acquiring an
      impressive research concern and called upon to expand more with the rising of its
      applications. As localization is gaining prominence in wireless sensor network,
      it is vulnerable to jamming attacks. Jamming attacks disrupt communication
      opportunity among the sender and receiver and deeply impact the localization
      process, leading to a huge error of the estimated sensor node position.
      Therefore, detection and elimination of jamming influence are absolutely
      indispensable. Range-based techniques especially Received Signal Strength (RSS)
      is facing severe impact of these attacks. This paper proposes algorithms based on
      Combination Multiple Frequency Multiple Power Localization (C-MFMPL) and Step
      Function Multiple Frequency Multiple Power Localization (SF-MFMPL). The
      algorithms have been tested in the presence of multiple types of jamming attacks
      including capture and replay, random and constant jammers over a log normal
      shadow fading propagation model. In order to overcome the impact of random and
      constant jammers, the proposed method uses two sets of frequencies shared by the
      implemented anchor nodes to obtain the averaged RSS readings all over the
      transmitted frequencies successfully. In addition, three stages of filters have
      been used to cope with the replayed beacons caused by the capture and replay
      jammers. In this paper the localization performance of the proposed algorithms
      for the ideal case which is defined by without the existence of the jamming
      attack are compared with the case of jamming attacks. The main contribution of
      this paper is to achieve robust localization performance in the presence of
      multiple jamming attacks under log normal shadow fading environment with a
      different simulation conditions and scenarios.

PMID- 28493978
TI  - Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in
      breast cancer.
AB  - Metastasis is the ultimate cause of breast cancer related mortality. Epithelial
      mesenchymal transition (EMT) is thought to play a crucial role in the metastatic
      potential of breast cancer. Growing evidence has implicated the SUMO E3 ligase
      PIAS1 in the regulation of EMT in mammary epithelial cells and breast cancer
      metastasis. However, the relevance of PIAS1 in human cancer and mechanisms by
      which PIAS1 might regulate breast cancer metastasis remain to be elucidated.
      Using tissue-microarray analysis (TMA), we report that the protein abundance and
      subcellular localization of PIAS1 correlate with disease specific overall
      survival of a cohort of breast cancer patients. In mechanistic studies, we find
      that PIAS1 acts via sumoylation of the transcriptional regulator SnoN to suppress
      invasive growth of MDA-MB-231 human breast cancer cell-derived organoids. Our
      studies thus identify the SUMO E3 ligase PIAS1 as a prognostic biomarker in
      breast cancer, and suggest a potential role for the PIAS1-SnoN sumoylation
      pathway in controlling breast cancer metastasis.

PMID- 28493979
TI  - Tissue lithography: Microscale dewaxing to enable retrospective studies on
      formalin-fixed paraffin-embedded (FFPE) tissue sections.
AB  - We present a new concept, termed tissue lithography (TL), and its implementation
      which enables retrospective studies on formalin-fixed paraffin-embedded tissue
      sections. Tissue lithography uses a microfluidic probe to remove microscale areas
      of the paraffin layer on formalin-fixed paraffin-embedded biopsy samples. Current
      practices in sample utilization for research and diagnostics require complete
      deparaffinization of the sample prior to molecular testing. This imposes strong
      limitations in terms of the number of tests as well as the time when they can be
      performed on a single sample. Microscale dewaxing lifts these constraints by
      permitting deprotection of a fraction of a tissue for testing while keeping the
      remaining of the sample intact for future analysis. After testing, the sample can
      be sent back to storage instead of being discarded, as is done in standard
      workflows. We achieve this microscale dewaxing by hydrodynamically confining
      nanoliter volumes of xylene on top of the sample with a probe head. We
      demonstrate micrometer-scale, chromogenic and fluorescence-based
      immunohistochemistry against multiple biomarkers (p53, CD45, HER2 and beta-actin)
      on tonsil and breast tissue sections and microarrays. We achieve stain patterns
      as small as 100 MUm * 50 MUm as well as multiplexed immunostaining within a
      single tissue microarray core with a 20-fold time reduction for local dewaxing as
      compared to standard protocols. We also demonstrate a 10-fold reduction in the
      rehydration time, leading to lower processing times between different stains. We
      further show the potential of TL for retrospective studies by sequentially
      dewaxing and staining four individual cores within the same tissue microarray
      over four consecutive days. By combining tissue lithography with the concept of
      micro-immunohistochemistry, we implement each step of the IHC protocol-dewaxing,
      rehydration and staining-with the same microfluidic probe head. Tissue
      lithography brings a new level of versatility and flexibility in sample
      processing and budgeting in biobanks, which may alleviate current sample
      limitations for retrospective studies in biomarker discovery and drug screening.

PMID- 28493980
TI  - Characterization of the juvenile green turtle (Chelonia mydas) microbiome
      throughout an ontogenetic shift from pelagic to neritic habitats.
AB  - The gut microbiome of herbivorous animals consists of organisms that efficiently
      digest the structural carbohydrates of ingested plant material. Green turtles
      (Chelonia mydas) provide an interesting model of change in these microbial
      communities because they undergo a pronounced shift from a surface-pelagic
      distribution and omnivorous diet to a neritic distribution and herbivorous diet.
      As an alternative to direct sampling of the gut, we investigated the cloacal
      microbiomes of juvenile green turtles before and after recruitment to neritic
      waters to observe any changes in their microbial community structure. Cloacal
      swabs were taken from individual turtles for analysis of the 16S rRNA gene
      sequences using Illumina sequencing. One fecal sample was also obtained, allowing
      for a preliminary comparison with the bacterial community of the cloaca. We found
      significant variation in the juvenile green turtle bacterial communities between
      pelagic and neritic habitats, suggesting that environmental and dietary factors
      support different bacterial communities in green turtles from these habitats.
      This is the first study to characterize the cloacal microbiome of green turtles
      in the context of their ontogenetic shifts, which could provide valuable insight
      into the origins of their gut bacteria and how the microbial community supports
      their shift to herbivory.

PMID- 28493981
TI  - Within-session decrement of the emission of licking bursts following reward
      devaluation in rats licking for sucrose.
AB  - We previously observed that dopamine D2-like receptor blockade in rats licking
      for sucrose produced a within-session decrement of the emission of licking bursts
      similar to the effect of either reward devaluation, or neuroleptics, on operant
      responding for different rewards, which, accordingly, we interpreted as an
      extinction-like effect. This implies that exposing animals to reward devaluation
      would result in a drop of burst number taking place only after the contact with
      the devalued reward. To test this prediction, we compared the difference in the
      within-session time course of burst number in response to high (10%) versus low
      (2%) concentration sucrose solutions, either in a condition of reward devaluation
      (exposure to 2% after daily 10%), or in a condition which does not involve
      changes in the reward value (two groups of subjects each repeatedly exposed to
      only one of the two concentrations). Reward devaluation resulted in a within
      session decrement of the burst number, with the response rate dropping only after
      the contact with the devalued reward, as predicted. This response pattern was
      reliably observed only in subjects at their first devaluation experience. In
      contrast, exposure of separate groups of animals to the two different
      concentrations yielded lower levels of burst number in the low concentration
      group apparent since the beginning of the session, as previously observed with
      dopamine D1-like receptor blockade. These results show that the analysis of burst
      number, but not of burst size, reveals a specific activation pattern in response
      to reward devaluation, which differs from the pattern observed comparing the
      response to two different sucrose concentrations in separate groups of subjects,
      i.e. in a condition not involving reward devaluation. Finally, the
      characterisation of the experimental measures of the analysis of licking
      microstructure in behaviourally (and psychologically) meaningful functional
      terms, might be relevant for the investigation of the mechanisms underlying
      behavioural activation and the related evaluation processes.

PMID- 28493982
TI  - Comparison of spectral-domain optical coherence tomography for intra-retinal
      layers thickness measurements between healthy and diabetic eyes among Chinese
      adults.
AB  - PURPOSE: To compare intra-retinal layer thickness measurements between eyes with
      no or mild diabetic retinopathy (DR) and age-matched controls using Spectralis
      spectral-domain optical coherence tomography (SD-OCT). METHODS: Cross-sectional
      observational analysis study. High-resolution macular volume scans (30 degrees  *
      25 degrees ) were obtained for 133 type 2 diabetes mellitus (T2DM) patients with
      no DR, 42 T2DM patients with mild DR and 115 healthy controls. The mean thickness
      was measured in all 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors
      for 8 separate layers, inner retinal layer (IRL), outer retinal layer (ORL) and
      total retina (TR), after automated segmentation. The ETDRS grid consisted of
      three concentric circles of 1-, 3-, and 6-mm diameter. The superior, inferior,
      temporal, and nasal sectors of the 3- and 6-mm circles were respectively
      designated as S3, I3, T3, and N3 and S6, I6, T6, and N6. Linear regression
      analyses were conducted to evaluate the associations between the intra-retinal
      layer thicknesses, age, diabetes duration, fasting blood glucose and HbA1c.
      RESULTS: The mean age and duration of T2DM were 61.1 and 13.7 years,
      respectively. Although no significant differences in the average TR and ORL
      volumes were observed among the groups, significant differences were found in the
      volume and sectorial thicknesses of the inner plexiform layer (IPL), outer
      plexiform layer (OPL) and IRL among the groups. In particular, the thicknesses of
      the IPL (S3, T3, S6, I6 and T6 sectors) and the IRL (S6 sector) were decreased in
      the no-DR group compared with the controls (P < 0.05). The thickness of the OPL
      (S3, N3, S6 and N6 sectors) was thinner in the no-DR group than in mild DR (P <
      0.05). The average IPL thickness was significantly negatively correlated with age
      and the duration of diabetes. CONCLUSION: The assessment of the intra-retinal
      layer thickness showed a significant decrease in the IPL and IRL thicknesses in
      Chinese adults with T2DM, even in the absence of visible microvascular signs of
      DR.

PMID- 28493983
TI  - New opportunities and challenges to engineer disease resistance in cassava, a
      staple food of African small-holder farmers.

PMID- 28493984
TI  - Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid
      sensitivity in asthmatic children.
AB  - BACKGROUND: Many asthmatic patients exhibit uncontrolled asthma despite high-dose
      inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct
      activation profiles that can influence ICS response. OBJECTIVES: A pilot study to
      identify gene expression markers of AEC dysfunction and markers of corticosteroid
      sensitivity in asthmatic and non-asthmatic control children, for comparison with
      published reports in adults. METHODS: AEC were obtained by nasal brushings and
      primary submerged cultures, and incubated in control conditions or in the
      presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based
      expression of FKBP51 (a steroid hormone receptor signalling regulator), NF-kB, IL
      6, LIF (an IL-6 family neurotrophic cytokine), serpinB2 (which inhibits
      plasminogen activation and promotes fibrin deposition) and porin (a marker of
      mitochondrial mass) were determined. RESULTS: 6 patients without asthma (median
      age 11yr; min-max: 7-13), 8 with controlled asthma (11yr, 7-13; median daily
      fluticasone dose = 100 MUg), and 4 with uncontrolled asthma (12yr, 7-14; 1000 MUg
      fluticasone daily) were included. Baseline expression of LIF mRNA was
      significantly increased in uncontrolled vs controlled asthmatic children.
      TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar
      trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51
      expression in all groups but the response was blunted in asthmatic children. No
      significant upregulation was identified regarding NF-kB, serpinB2 and porin.
      CONCLUSION: LIF and FKBP51 expression in epithelial cells were the most
      interesting markers of AEC dysfunction/response to corticosteroid treatment.

PMID- 28493985
TI  - Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin
      conjugate 4I: In vitro and in vivo studies.
AB  - Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective
      therapeutic modality to eradicate drug resistant bacteria without provoking
      multidrug resistance, has attracted increasing attention. This study examined the
      antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I
      with four lysine groups against two different clinical isolated strains (drug
      sensitive and multidrug resistant) of the Acinetobacter baumannii species and its
      toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect
      of PACT on acute, potentially lethal multidrug resistant strain excisional wound
      infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high
      antimicrobial efficacy on two different strains due to a high yield of reactive
      oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation
      effects of 4I against two different strains were dose-dependent. At 3.9 MUM and
      7.8 MUM, PACT induced 6 log units of inactivation of sensitive and multidrug
      resistant strains. In contrast, 4I alone and illumination alone treatments had no
      visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great
      safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I
      mediated PACT was not only able to kill bacteria but also accelerated wound
      recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug
      resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h
      post-treatment. These results imply that 4I-mediated PACT therapy is an effective
      and safe alternative to conventional antibiotic therapy and has clinical
      potential for superficial drug-resistant bacterial infections.

PMID- 28493987
TI  - Barriers to utilization of childbirth services of a rural birthing center in
      Nepal: A qualitative study.
AB  - BACKGROUND: Maternal mortality and morbidity are public health problems in Nepal.
      In rural communities, many women give birth at home without the support of a
      skilled birth attendant, despite the existence of rural birthing centers. The aim
      of this study was to explore the barriers and provide pragmatic recommendations
      for better service delivery and use of rural birthing centers. METHODS: We
      conducted 26 in-depth interviews with service users and providers, and three
      focus group discussions with community key informants in a rural community of
      Rukum district. We used the Adithya Cattamanchi logic model as a guiding
      framework for data analysis. RESULTS: Irregular and poor quality services,
      inadequate human and capital resources, and poor governance were health system
      challenges which prevented service delivery. Contextual barriers including
      difficult geography, poor birth preparedness practices, harmful culture practices
      and traditions and low level of trust were also found to contribute to
      underutilization of the birthing center. CONCLUSION: The rural birthing center
      was not providing quality services when women were in need, which meant women did
      not use the available services properly because of systematic and contextual
      barriers. Approaches such as awareness-raising activities, local resource
      mobilization, ensuring access to skilled providers and equipment and other long
      term infrastructure development works could improve the quality and utilization
      of childbirth services in the rural birthing center. This has resonance for other
      centers in Nepal and similar countries.

PMID- 28493986
TI  - Impact of treatment in long-term survival patients with follicular lymphoma: A
      Spanish Lymphoma Oncology Group registry.
AB  - BACKGROUND: Follicular lymphoma is the second most common non-Hodgkin lymphoma in
      the United States and Europe. However, most of the prospective randomized studies
      have very little follow-up compared to the long natural history of the disease.
      The primary aim of this study was to investigate the long-term survival of our
      series of patients with follicular lymphoma. PATIENTS AND METHODS: A total of
      1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were
      prospectively enrolled from 1980 to 2013. RESULTS: Median follow-up was 54.9
      months and median overall survival is over 20 years in our series. We analyzed
      the patients who are still alive beyond 10 years from diagnosis in order to fully
      assess the prognostic factors that condition this group. Out of 166 patients who
      are still alive after more than 10 years of follow-up, 118 of them (73%) are free
      of evident clinical disease. Variables significantly associated with survival at
      10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p
      <0.002), normal beta2 microglobulin (p <0.005), no B symptoms upon diagnosis (p
      <0.02), Performance Status 0-1 (p <0.03) and treatment with anthracyclines and
      rituximab (p <0.001), or rituximab (p <0.0001). CONCLUSIONS: A longer follow-up
      and a large series demonstrated a substantial population of patients with
      follicular lymphoma free of disease for more than 10 years.

PMID- 28493988
TI  - Prediction of whole-body fat percentage and visceral adipose tissue mass from
      five anthropometric variables.
AB  - BACKGROUND: The conventional measurement of obesity utilises the body mass index
      (BMI) criterion. Although there are benefits to this method, there is concern
      that not all individuals at risk of obesity-associated medical conditions are
      being identified. Whole-body fat percentage (%FM), and specifically visceral
      adipose tissue (VAT) mass, are correlated with and potentially implicated in
      disease trajectories, but are not fully accounted for through BMI evaluation. The
      aims of this study were (a) to compare five anthropometric predictors of %FM and
      VAT mass, and (b) to explore new cut-points for the best of these predictors to
      improve the characterisation of obesity. METHODS: BMI, waist circumference (WC),
      waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist/height0.5
      (WHT.5R) were measured and calculated for 81 adults (40 women, 41 men; mean (SD)
      age: 38.4 (17.5) years; 94% Caucasian). Total body dual energy X-ray
      absorptiometry with Corescan (GE Lunar iDXA, Encore version 15.0) was also
      performed to quantify %FM and VAT mass. Linear regression analysis, stratified by
      sex, was applied to predict both %FM and VAT mass for each anthropometric
      variable. Within each sex, we used information theoretic methods (Akaike
      Information Criterion; AIC) to compare models. For the best anthropometric
      predictor, we derived tentative cut-points for classifying individuals as obese
      (>25% FM for men or >35% FM for women, or > highest tertile for VAT mass).
      RESULTS: The best predictor of both %FM and VAT mass in men and women was WHtR.
      Derived cut-points for predicting whole body obesity were 0.53 in men and 0.54 in
      women. The cut-point for predicting visceral obesity was 0.59 in both sexes.
      CONCLUSIONS: In the absence of more objective measures of central obesity and
      adiposity, WHtR is a suitable proxy measure in both women and men. The proposed
      DXA-%FM and VAT mass cut-offs require validation in larger studies, but offer
      potential for improvement of obesity characterisation and the identification of
      individuals who would most benefit from therapeutic intervention.

PMID- 28493989
TI  - Dynamics of initial drop splashing on a dry smooth surface.
AB  - We simulate the onset and evolution of the earliest splashing of an infinite
      cylindrical liquid drop on a smooth dry solid surface. A tiny splash is observed
      to be emitted out of the rim of the lamella in the early stage of the impact. We
      find that the onset time of the splash is primarily dependent on the
      characteristic timescale, which is defined by the impact velocity as well as the
      drop radius, with no strong dependence on either the liquid viscosity or surface
      tension. Three regimes are found to be responsible for different splashing
      patterns. The outermost ejected droplets keep extending radially at a uniform
      speed proportional to the impact speed. Finally, we discuss the underlying
      mechanism which is responsible for the occurrence of the initial drop splash in
      the study.

PMID- 28493990
TI  - MiR-338-3p regulates neuronal maturation and suppresses glioblastoma
      proliferation.
AB  - Neurogenesis is a highly-regulated process occurring in the dentate gyrus that
      has been linked to learning, memory, and antidepressant efficacy. MicroRNAs
      (miRNAs) have been previously shown to play an important role in the regulation
      of neuronal development and neurogenesis in the dentate gyrus via modulation of
      gene expression. However, this mode of regulation is both incompletely described
      in the literature thus far and highly multifactorial. In this study, we designed
      sensors and detected relative levels of expression of 10 different miRNAs and
      found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of
      miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is
      expressed most highly in the mature neuron. We also designed a viral "sponge" to
      knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down,
      neurons sprout multiple primary dendrites that branch off of the soma in a
      disorganized manner, cellular proliferation is upregulated, and neoplasms form
      spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma
      cell lines slows their proliferation in vitro. Further, low miR-338-3p expression
      is associated with increased mortality and disease progression in patients with
      glioblastoma. These data identify miR-338-3p as a clinically relevant tumor
      suppressor in glioblastoma.

PMID- 28493991
TI  - Changes in gene expression between a soybean F1 hybrid and its parents are
      associated with agronomically valuable traits.
AB  - Soybean [Glycine max (L.) Merr.] genetic diversity is limited because
      domesticated soybean has undergone multiple genetic bottlenecks. Its progenitor,
      the wild soybean [Glycine soja Siebold & Zucc], has not undergone the same
      intense selection and is much more genetically diverse than domesticated soybean.
      However, the agronomic importance of diversity in wild soybean is unclear, and
      its weedy nature makes assessment difficult. To address this issue, we chose for
      study a highly selected, adapted F4-derived progeny of wild soybean, NMS4-44-329.
      This breeding line is derived from the hybridization between G. max cultivar
      N7103 and G. soja PI 366122. Agronomic comparisons were made among N7103, NMS4-44
      329 and their F1 and F2 progeny in replicated yield trials at two North Carolina
      locations. Significant F1 mid-parent heterosis was observed at each location for
      seed yield (189 and 223 kgha-1, P<0.05 and P<0.10, respectively), seed protein
      content (1.1g/100g, P<0.01) and protein production per hectare (101 and 100 kgha
      1, P<0.01 and P<0.06, respectively). Increased yield, seed protein content and
      protein production per hectare in the hybrids suggested that wild soybean has the
      potential to improve agronomic traits in applied breeding. Comparisons of
      differentially-expressed genes in the hybrid vs. parents identified genes
      associated with N metabolism. Non-additive changes in gene expression in the
      hybrids relative to the parents could reasonably explain the improved protein
      levels in the F1 hybrids. Changes in gene expression were influenced by
      environmental effects; however, allele specific bias in the hybrids were well
      correlated between environments. We propose that changes in gene expression, both
      additive and non-additive, and changes in allele specific expression bias may
      explain agronomic traits, and be valuable tools for plant breeders in the
      assessment of breeding populations.

PMID- 28493992
TI  - Correction: Distribution and evolution of stable single alpha-helices (SAH
      domains) in myosin motor proteins.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174639.].

PMID- 28493993
TI  - Mechanism of down regulation of Na-H exchanger-2 in experimental colitis.
AB  - BACKGROUND: The Na-H exchanger [NHE] performs an electroneutral uptake of NaCl
      and water from the lumen of the gastrointestinal tract. There are several
      distinct NHE isoforms, some of which show an altered expression in the
      inflammatory bowel diseases (IBD). In this study, we examined a role of NHE-2 in
      experimental colitis. METHODS: Colitis was induced in male Sprague-Dawley rats by
      intra-rectal administration of trinitrobenzenesulphonic acid (TNBS). On day 6
      post-TNBS, the animals were sacrificed, colonic and ileal segments were taken
      out, cleaned with phosphate buffered saline and used in this study. RESULTS:
      There was a significant decrease in the level of NHE-2 protein as measured by ECL
      western blot analysis and confocal immunofluorescence microscopy. The levels of
      NHE-2 mRNA and heteronuclear RNA measured by an end-point RT-PCR and a real time
      PCR were also decreased significantly in the inflamed colon. However, there was
      no change in the level of NHE-2 protein in response to in vitro TNF-alpha
      treatment of uninflamed rat colonic segment. These changes were selective and
      localized to the colon as actin, an internal control, remained unchanged.
      Confocal immunofluorescence microscopy revealed co-localization of NHE-2 and NHE
      3 in the brush borders of colonic epithelial cells. Inflamed colon showed a
      significant increase in myeloperoxidase activity and colon hypertrophy. In
      addition, there was a significant decrease in body weight and goblet cells' mucin
      staining in the TNBS treated colon. These changes were not conspicuous in the non
      inflamed ileum. CONCLUSIONS: These findings demonstrate suppression of NHE-2
      expression on the brush borders in the colonic epithelial cells which is
      regulated transcriptionally. However a role of TNF-alpha in the regulation of NHE
      2 is discounted in the present model of colitis. This decrease in the NHE-2
      expression will lead to a loss of electrolyte and water uptake thus contributing
      to the symptoms associated with IBD.

PMID- 28493995
TI  - Influence of site index on the relationship between forest net primary
      productivity and stand age.
AB  - Previous studies show that forest net primary productivity (NPP) varies
      pronouncedly with stand age, and these variations play a crucial role in
      determining forest carbon sinks or sources at regional scales. Some forest carbon
      cycling models, eg. InTEC (The integrated terrestrial ecosystem C-budget model),
      calculates annual forest NPP in the long term according to normalized NPP-age
      relationships and the reference forest NPP at a given age. Therefore, the
      accurate NPP-age relationship is important for forest NPP estimation. In this
      study, NPP at various stand ages for twelve major forest stand types in
      Heilongjiang Province in northeast China is derived from yield tables with
      consideration of the total biomass increment and foliage and fine-root turnovers.
      Similar to previous studies, our results also show that forest NPP increases
      quickly at young ages, reaches the maximum value at middle age (10-40 years old),
      and then decreases to a relative stable level at old ages. However, we
      additionally found that forests under better site conditions have faster growth
      rates in young ages and steeper declines after reaching the maximum. Therefore,
      when the NPP-age curves for different site indices are normalized against the
      maximum value of each curve, there are significant differences among them. These
      differences have implications on the methodology for estimating the spatial
      distribution of forest carbon sources and sinks.

PMID- 28493994
TI  - Spatiotemporal analysis of microbial community dynamics during seasonal
      stratification events in a freshwater lake (Grand Lake, OK, USA).
AB  - Many freshwater lakes undergo seasonal stratification, where the formation of
      phototrophic blooms in the epilimnion and subsequent sedimentation induces
      hypoxia/anoxia in the thermocline and hypolimnion. This autochthonously produced
      biomass represents a major seasonal organic input that impacts the entire
      ecosystem. While the limnological aspects of this process are fairly well
      documented, relatively little is known regarding the microbial community response
      to such events, especially in the deeper anoxic layers of the water column. Here,
      we conducted a spatiotemporal survey of the particle-associated and free-living
      microbial communities in a warm monomictic freshwater reservoir (Grand Lake O'
      the Cherokees) in northeastern Oklahoma, USA. Pre-stratification samples (March)
      harbored a homogeneous community throughout the oxygenated water column dominated
      by typical oligotrophic aquatic lineages (acl clade within Actinobacteria, and
      Flavobacterium within the Bacteroidetes). The onset of phototrophic blooming in
      June induced the progression of this baseline community into two distinct
      trajectories. Within the oxic epilimnion, samples were characterized by the
      propagation of phototrophic (Prochlorococcus), and heterotrophic (Planctomycetes,
      Verrucomicrobia, and Beta-Proteobacteria) lineages. Within the oxygen-deficient
      thermocline and hypolimnion, the sedimentation of surface biomass induced the
      development of a highly diverse community, with the enrichment of Chloroflexi,
      "Latescibacteria", Armatimonadetes, and Delta-Proteobacteria in the particle
      associated fraction, and Gemmatimonadetes and "Omnitrophica" in the free-living
      fraction. Our work documents the development of multiple spatially and temporally
      distinct niches during lake stratification, and supports the enrichment of
      multiple yet-uncultured and poorly characterized lineages in the lake's deeper
      oxygen-deficient layers, an ecologically relevant microbial niche that is often
      overlooked in lakes diversity surveys.

PMID- 28493996
TI  - Left ventricular functional, structural and energetic effects of normal aging:
      Comparison with hypertension.
AB  - OBJECTIVES: Both aging and hypertension are significant risk factors for heart
      failure in the elderly. The purpose of this study was to determine how aging,
      with and without hypertension, affects left ventricular function. METHODS: Cross
      sectional study of magnetic resonance imaging and 31P spectroscopy-based
      measurements of left ventricular structure, global function, strains, pulse wave
      velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated
      hypertensive patients (though no other cardiovascular disease or diabetes)
      stratified into 3 age deciles from 50-79 years. RESULTS: Normal aging was
      associated with significant increases in systolic blood pressure, vascular
      stiffness, torsion, and impaired diastolic function (all P<0.05). Age-matched
      hypertension exacerbated the effects of aging on systolic pressure, and diastolic
      function. Hypertension alone, and not aging, was associated with increased left
      ventricular mass index, reduced energetic reserve, reduced longitudinal
      shortening and increased endocardial circumferential shortening (all P<0.05).
      Multiple linear regression analysis showed that these unique hypertensive
      features were significantly related to systolic blood pressure (P<0.05).
      CONCLUSIONS: 1) Hypertension adds to the age-related changes in systolic blood
      pressure and diastolic function; 2) hypertension is uniquely associated with
      changes in several aspects of left ventricular structure, function, systolic
      strains, and energetics; and 3) these uniquely hypertensive-associated parameters
      are related to the level of systolic blood pressure and so are potentially
      modifiable.

PMID- 28493998
TI  - Metabolomics analysis: Finding out metabolic building blocks.
AB  - In this paper we propose a new methodology for the analysis of metabolic
      networks. We use the notion of strongly connected components of a graph, called
      in this context metabolic building blocks. Every strongly connected component is
      contracted to a single node in such a way that the resulting graph is a directed
      acyclic graph, called a metabolic DAG, with a considerably reduced number of
      nodes. The property of being a directed acyclic graph brings out a background
      graph topology that reveals the connectivity of the metabolic network, as well as
      bridges, isolated nodes and cut nodes. Altogether, it becomes a key information
      for the discovery of functional metabolic relations. Our methodology has been
      applied to the glycolysis and the purine metabolic pathways for all organisms in
      the KEGG database, although it is general enough to work on any database. As
      expected, using the metabolic DAGs formalism, a considerable reduction on the
      size of the metabolic networks has been obtained, specially in the case of the
      purine pathway due to its relative larger size. As a proof of concept, from the
      information captured by a metabolic DAG and its corresponding metabolic building
      blocks, we obtain the core of the glycolysis pathway and the core of the purine
      metabolism pathway and detect some essential metabolic building blocks that
      reveal the key reactions in both pathways. Finally, the application of our
      methodology to the glycolysis pathway and the purine metabolism pathway reproduce
      the tree of life for the whole set of the organisms represented in the KEGG
      database which supports the utility of this research.

PMID- 28493999
TI  - Leopard in a tea-cup: A study of leopard habitat-use and human-leopard
      interactions in north-eastern India.
AB  - There is increasing evidence of the importance of multi-use landscapes for the
      conservation of large carnivores. However, when carnivore ranges overlap with
      high density of humans, there are often serious conservation challenges. This is
      especially true in countries like India where loss of peoples' lives and property
      to large wildlife are not uncommon. The leopard (Panthera pardus) is a large
      felid that is widespread in India, often sharing landscapes with high human
      densities. In order to understand the ecology of leopards in a human use
      landscape and the nature of human-leopard interactions, we studied (i) the
      spatial and temporal distribution and the characteristics of leopard attacks on
      people, (ii) the spatial variability in the pattern of habitat use by the
      leopard, and (iii) the spatial relationship between attack locations and habitat
      use by leopards. The study site, located in northern West Bengal, India, is a
      densely populated mixed-use landscape of 630 km2, comprising of forests, tea
      plantations, agriculture fields, and human settlements. A total of 171 leopard
      attacks on humans were reported between January 2009 and March 2016, most of
      which occurred within the tea-gardens. None of the attacks was fatal. We found
      significant spatial clustering of locations of leopard attacks on humans.
      However, most of the attacks were restricted to certain tea estates and occurred
      mostly between January and May. Analysis of habitat use by leopards showed that
      the probability of use of areas with more ground vegetation cover was high while
      that of areas with high density of buildings was low. However, locations of
      leopard attacks on people did not coincide with areas that showed a higher
      probability of use by leopards. This indicates that an increased use of an area
      by leopards, by itself, does not necessarily imply an increase in attacks on
      people. The spatial and temporal clustering of attack locations allowed us to use
      this information to prioritize areas to focus mitigation activities in order
      reduce negative encounters between people and leopards in this landscape which
      has had a long history of conflict.

PMID- 28493997
TI  - Adenosine A1 receptor activation increases myocardial protein S-nitrosothiols and
      elicits protection from ischemia-reperfusion injury in male and female hearts.
AB  - Nitric oxide (NO) plays an important role in cardioprotection, and recent work
      from our group and others has implicated protein S-nitrosylation (SNO) as a
      critical component of NO-mediated protection in different models, including
      ischemic pre- and post-conditioning and sex-dependent cardioprotection. However,
      studies have yet to examine whether protein SNO levels are similarly increased
      with pharmacologic preconditioning in male and female hearts, and whether an
      increase in protein SNO levels, which is protective in male hearts, is sufficient
      to increase baseline protection in female hearts. Therefore, we pharmacologically
      preconditioned male and female hearts with the adenosine A1 receptor agonist N6
      cyclohexyl adenosine (CHA). CHA administration prior to ischemia significantly
      improved functional recovery in both male and female hearts compared to baseline
      in a Langendorff-perfused heart model of ischemia-reperfusion injury (% of
      preischemic function +/- SE: male baseline: 37.5+/-3.4% vs. male CHA: 55.3+/
      3.2%; female baseline: 61.4+/-5.7% vs. female CHA: 76.0+/-6.2%). In a separate
      set of hearts, we found that CHA increased p-Akt and p-eNOS levels. We also used
      SNO-resin-assisted capture with LC-MS/MS to identify SNO proteins in male and
      female hearts, and determined that CHA perfusion induced a modest increase in
      protein SNO levels in both male (11.4%) and female (12.3%) hearts compared to
      baseline. These findings support a potential role for protein SNO in a model of
      pharmacologic preconditioning, and provide evidence to suggest that a modest
      increase in protein SNO levels is sufficient to protect both male and female
      hearts from ischemic injury. In addition, a number of the SNO proteins identified
      with CHA treatment were also observed with other forms of cardioprotective
      stimuli in prior studies, further supporting a role for protein SNO in
      cardioprotection.

PMID- 28494000
TI  - Validating Bayesian truth serum in large-scale online human experiments.
AB  - Bayesian truth serum (BTS) is an exciting new method for improving honesty and
      information quality in multiple-choice survey, but, despite the method's
      mathematical reliance on large sample sizes, existing literature about BTS only
      focuses on small experiments. Combined with the prevalence of online survey
      platforms, such as Amazon's Mechanical Turk, which facilitate surveys with
      hundreds or thousands of participants, BTS must be effective in large-scale
      experiments for BTS to become a readily accepted tool in real-world applications.
      We demonstrate that BTS quantifiably improves honesty in large-scale online
      surveys where the "honest" distribution of answers is known in expectation on
      aggregate. Furthermore, we explore a marketing application where "honest" answers
      cannot be known, but find that BTS treatment impacts the resulting distributions
      of answers.

PMID- 28494001
TI  - Partial spleen embolization reduces the risk of portal hypertension-induced upper
      gastrointestinal bleeding in patients not eligible for TIPS implantation.
AB  - INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a severe and life
      threatening complication among patients with portal hypertension (PH). Covered
      transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice
      for patients with refractory or recurrent UGIB despite pharmacological and
      endoscopic therapy. In some patients, TIPS implantation is not possible due to co
      morbidity or vascular disorders. Spleen embolization (SE) may be a promising
      alternative in this setting. MATERIALS AND METHODS: We retrospectively analyzed 9
      patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All
      patients met the following criteria: (i) upper gastrointestinal hemorrhage with
      primary or secondary failure of endoscopic interventions and (ii) TIPS
      implantation not possible. Each patient was followed for at least 6 months after
      embolization. RESULTS: Five patients (56%) suffered from cirrhotic PH, 4 patients
      (44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from
      gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and
      finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the
      patients treated with partial SE experienced re-bleeding episodes or required
      blood transfusions during a total follow-up time of 159 months, including both
      patients with cirrhotic- and non-cirrhotic PH. DISCUSSION: Partial SE, as a
      minimally invasive intervention with low procedure-associated complications, may
      be a valuable alternative for patients with recurrent PH-induced UGIB refractory
      to standard therapy.

PMID- 28494002
TI  - Involvement of Band3 in the efflux of sphingosine 1-phosphate from erythrocytes.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator that is thought to be
      involved in various diseases. Although the main source of S1P in the plasma is
      erythrocytes, how S1P is exported from erythrocytes has not been elucidated. When
      we differentiated K562 cells into erythroblast-like cells with sodium butyrate,
      we observed that the efflux of S1P was increased without increased expression of
      previously proposed S1P transporters, while the expression levels of Band3 were
      increased. Therefore, in this study, we investigated the involvement of Band 3,
      the most characteristic membranous transporter for erythrocytes, in S1P efflux,
      using 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid, disodium salt
      (H2DIDS), which is an inhibitor of Band3. First, we treated human washed
      erythrocytes with H2DIDS and found that H2DIDS decreased the S1P levels in the
      supernatant, while it increased the cellular S1P contents. Next, when we injected
      H2DIDS into mice, the plasma S1P level was significantly decreased. Finally, when
      we overexpressed or suppressed Band3 in K562 cells, S1P efflux was enhanced or
      decreased, respectively, while the overexpression of Band3 in HEK293 cells did
      not modulate S1P efflux. These results suggested the possible involvement of
      Band3 in the transport of S1P, a multi-functional bioactive phospholipid, from
      erythrocytes.

PMID- 28494004
TI  - Increasing land-use intensity reverses the relative occupancy of two quadrupedal
      scavengers.
AB  - Human land use is continuously altering the natural environment, yet the greater
      ecological implications of this change for many groups that are key to healthy
      ecosystem functioning remains uncharacterised in the tropics. Terrestrial
      scavenging vertebrates are one such group, providing integral ecosystem services
      through the removal of carrion which is a crucial component of both nutrient
      cycling and disease dynamics. To explore how anthropogenic processes may affect
      forest scavengers, we investigated the changes in the relative occupancy of two
      important terrestrial scavengers along a gradient of land use intensity, ranging
      from protected forest to oil palm plantation in Borneo. We found the Malay civet
      (Viverra tangalunga) had highest, albeit variable, occupancy in areas of low land
      use intensity and the Southeast Asian water monitor (Varanus salvator
      macromaculatus) had highest occupancy in areas of high land use intensity. Land
      use had no effect on the combined occupancy of the two species. In high land use
      intensity sites, individual water monitors were larger and had better body
      condition, but at population level had a highly biased sex ratio with more males
      than females and increased signs of intraspecific conflict. We did not assess
      scavenging rate or efficiency as a process, but the high occupancy rates and
      apparent health of the scavengers in high land use intensity landscapes suggests
      this ecological process is robust to land use change.

PMID- 28494003
TI  - P2Y6 receptors are involved in mediating the effect of inactivated avian
      influenza virus H5N1 on IL-6 & CXCL8 mRNA expression in respiratory epithelium.
AB  - One of the key pathophysiologies of H5N1 infection is excessive proinflammatory
      cytokine response (cytokine storm) characterized by increases in IFN-beta, TNF
      alpha, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced
      cytokine release can occur via an infection-independent mechanism, however,
      detail of the cellular signaling involved is poorly understood. To elucidate this
      mechanism, the effect of inactivated (beta-propiolactone-treated) H5N1 on the
      cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial
      cells was investigated. We found that the inactivated-H5N1 increased mRNA for IL
      6 and CXCL8 but not TNF-alpha, CCL5 or CXCL10. This effect of the inactivated
      H5N1 was inhibited by sialic acid receptor inhibitor (alpha-2,3 sialidase),
      adenosine diphosphatase (apyrase), P2Y receptor (P2YR) inhibitor (suramin), P2Y6R
      antagonist (MRS2578), phospholipase C inhibitor (U73122), protein kinase C
      inhibitors (BIM and Go6976) and cell-permeant Ca2+ chelator (BAPTA-AM).
      Inhibitors of MAPK signaling, including of ERK1/2 (PD98059), p38 MAPK (SB203580)
      and JNK (SP600125) significantly suppressed the inactivated-H5N1-induced mRNA
      expression of CXCL8. On the other hand, the inactivated-H5N1-induced mRNA
      expression of IL-6 was inhibited by SB203580, but not PD98059 or SP600125,
      whereas SN-50, an inhibitor of NF-kappaB, inhibited the effect of virus on mRNA
      expression of both of IL-6 and CXCL8. Taken together, our data suggest that,
      without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by
      a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and
      alpha-2,3 sialic acid receptors at the cell membrane of host cells, and involves
      activation of P2Y6 purinergic receptors.

PMID- 28494005
TI  - Relationship between regulatory pattern of gene expression level and gene
      function.
AB  - Regulation of gene expression levels is essential for all living systems and
      transcription factors (TFs) are the main regulators of gene expression through
      their ability to repress or induce transcription. A balance between synthesis and
      degradation rates controls gene expression levels. To determine which rate is
      dominant, we analyzed the correlation between expression levels of a TF and its
      regulated gene based on a mathematical model. We selected about 280,000
      expression patterns of 355 TFs and 647 regulated genes using DNA microarray data
      from the Gene Expression Omnibus (GEO) data repository. Based on our model,
      correlation between the expressions of TF-regulated gene pairs corresponds to
      tuning of the synthesis rate, whereas no correlation indicates excessive
      synthesis and requires tuning of the degradation rate. The gene expression
      relationships between TF-regulated gene pairs were classified into four types
      that correspond to different gene regulatory mechanisms. It was surprising that
      fewer than 20% of these genes were governed by the familiar regulatory mechanism,
      i.e., through the synthesis rate. Moreover, we performed pathway analysis and
      found that each classification type corresponded to distinct gene functions:
      cellular regulation pathways were dominant in the type with synthesis rate
      regulation and terms associated with diseases such as cancer, Parkinson's
      disease, and Alzheimer's disease were dominant in the type with degradation rate
      regulation. Interestingly, these diseases are caused by the accumulation of
      proteins. These results indicated that gene expression is regulated structurally,
      not arbitrarily, according to the gene function. This funding is indicative of a
      systematic control of transcription processes at the whole-cell level.

PMID- 28494006
TI  - The change of longitudinal relaxation rate in oxygen enhanced pulmonary MRI
      depends on age and BMI but not diffusing capacity of carbon monoxide in healthy
      never-smokers.
AB  - OBJECTIVE: Oxygen enhanced pulmonary MRI is a promising modality for functional
      lung studies and has been applied to a wide range of pulmonary conditions. The
      purpose of this study was to characterize the oxygen enhancement effect in the
      lungs of healthy, never-smokers, in light of a previously established
      relationship between oxygen enhancement and diffusing capacity of carbon monoxide
      in the lung (DL,CO) in patients with lung disease. METHODS: In 30 healthy never
      smoking volunteers, an inversion recovery with gradient echo read-out (Snapshot
      FLASH) was used to quantify the difference in longitudinal relaxation rate, while
      breathing air and 100% oxygen, DeltaR1, at 1.5 Tesla. Measurements were performed
      under multiple tidal inspiration breath-holds. RESULTS: In single parameter
      linear models, DeltaR1 exhibit a significant correlation with age (p = 0.003) and
      BMI (p = 0.0004), but not DL,CO (p = 0.33). Stepwise linear regression of DeltaR1
      yields an optimized model including an age-BMI interaction term. CONCLUSION: In
      this healthy, never-smoking cohort, age and BMI are both predictors of the change
      in MRI longitudinal relaxation rate when breathing oxygen. However, DL,CO does
      not show a significant correlation with the oxygen enhancement. This is possibly
      because oxygen transfer in the lung is not diffusion limited at rest in healthy
      individuals. This work stresses the importance of using a physiological model to
      understand results from oxygen enhanced MRI.

PMID- 28494007
TI  - Child malnutrition in sub-Saharan Africa: A meta-analysis of demographic and
      health surveys (2006-2016).
AB  - BACKGROUND: Sub-Saharan Africa has one of the highest levels of child
      malnutrition globally. Therefore, a critical look at the distribution of
      malnutrition within its sub-regions is required to identify the worst affected
      areas. This study provides a meta-analysis of the prevalence of malnutrition
      indicators (stunting, wasting and underweight) within four sub-regions of sub
      Saharan Africa. METHODS: Cross-sectional data from the most recent Demographic
      and Health Surveys (2006-2016) of 32 countries in sub-Saharan Africa were used.
      The countries were grouped into four sub-regions (East Africa, West Africa,
      Southern Africa and Central Africa), and a meta-analysis was conducted to
      estimate the prevalence of each malnutrition indicator within each of the sub
      regions. Significant heterogeneity was detected among the various surveys (I2
      >50%), hence a random effect model was used, and sensitivity analysis was
      performed, to examine the effects of outliers. Stunting was defined as HAZ<-2;
      wasting as WHZ<-2 and underweight as WAZ<-2. RESULTS: Stunting was highest in
      Burundi (57.7%) and Malawi (47.1%) in East Africa; Niger (43.9%), Mali (38.3%),
      Sierra Leone (37.9%) and Nigeria (36.8%) in West Africa; Democratic Republic of
      Congo (42.7%) and Chad (39.9%) in Central Africa. Wasting was highest in Niger
      (18.0%), Burkina Faso (15.50%) and Mali (12.7%) in West Africa; Comoros (11.1%)
      and Ethiopia (8.70%) in East Africa; Namibia (6.2%) in Southern Africa; Chad
      (13.0%) and Sao Tome & Principle (10.5%) in Central Africa. Underweight was
      highest in Burundi (28.8%) and Ethiopia (25.2%) in East Africa; Niger (36.4%),
      Nigeria (28.7%), Burkina Faso (25.7%), Mali (25.0%) in West Africa; and Chad
      (28.8%) in Central Africa. CONCLUSION: The prevalence of malnutrition was highest
      within countries in East Africa and West Africa compared to the WHO Millennium
      development goals target for 2015. Appropriate nutrition interventions need to be
      prioritised in East Africa and West Africa if sub-Saharan Africa is to meet the
      WHO global nutrition target of improving maternal, infant and young child
      nutrition by 2025.

PMID- 28494008
TI  - Blocking of stromal interaction molecule 1 expression influence cell
      proliferation and promote cell apoptosis in vitro and inhibit tumor growth in
      vivo in head and neck squamous cell carcinoma.
AB  - Calcium signal plays an important role in a variety of cancer cell metabolism,
      but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is
      limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry
      mechanism that maintains calcium concentration and produces calcium signal in non
      excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1),
      which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many
      studies demonstrated that STIM1 and SOCE play important functions in the
      regulation of many cancer progressions, their clinical relevance in HNSCC remains
      unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC
      tissues compared with those in adjacent normal tissues. Meanwhile, this
      overexpression was close associated with tumor size but not with neck lymph node
      metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor
      growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2
      (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer
      cell line) with STIM1 expression level lower than previous two cell lines, were
      selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and
      Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell
      proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell
      apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER
      stress was amplified when STIM1 expression was downregulated but was attenuated
      as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models
      confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study
      provides new insight into HNSCC molecular mechanism and potential therapeutic
      target through targeting SOCE-dependent process. However, whether STIM1
      participates in HNSCC metastasis requires further study.

PMID- 28494009
TI  - Postnatal changes and sexual dimorphism in collagen expression in mouse skin.
AB  - To investigate sexual dimorphism and postnatal changes in skin collagen
      expression, mRNA levels of collagens and their regulatory factors in male and
      female skin were examined during the first 120 days of age by quantitative
      realtime PCR. Levels of mRNAs encoding extracellular matrices did not show any
      differences between male and female mice until day 15. Col1a1 and Col1a2 mRNAs
      noticeably increased at day 30 and remained at high levels until day 120 in male
      mice, while those in female mice remained at low levels during the period.
      Consistent with the mRNA expression, pepsin-soluble type I collagen contents in
      skin was very high in mature male as compared to female. Col3a1 mRNA in male mice
      also showed significantly high level at day 120 as compared to female. On the
      other hand, expression of mRNAs encoding TGF-betas and their receptors did not
      show apparent sexual dimorphism although small significant differences were
      observed at some points. Castration at 60 days of age resulted in a significant
      decrease in type I collagen mRNA expression within 3 days, and noticeably
      decreased expression of all fibril collagen mRNAs examined within 14 days, while
      administration of testosterone tube maintained the mRNA expression at high
      levels. Despite the in vivo effect of testosterone, administration of
      physiological concentrations of testosterone did not affect fibril collagen mRNA
      expression in either human or mouse skin fibroblasts in vitro, suggesting that
      testosterone does not directly affect collagen expression in fibroblasts. In
      summary, present study demonstrated dynamic postnatal changes in expression of
      collagens and their regulatory factors, and suggest that testosterone and its
      effects on collagen expression are responsible for the skin sexual dimorphism but
      the effects of testosterone is not due to direct action on dermal fibroblasts.

PMID- 28494010
TI  - Calcification in dermal fibroblasts from a patient with GGCX syndrome accompanied
      by upregulation of osteogenic molecules.
AB  - Gamma-glutamyl carboxylase (GGCX) gene mutation causes GGCX syndrome (OMIM:
      137167), which is characterized by pseudoxanthoma elasticum (PXE)-like symptoms
      and coagulation impairment. Here, we present a 55-year-old male with a novel
      homozygous deletion mutation, c.2,221delT, p.S741LfsX100, in the GGCX gene.
      Histopathological examination revealed calcium deposits in elastic fibers and
      vessel walls, and collagen accumulation in the mid-dermis. Studies of dermal
      fibroblasts from the patient (GGCX dermal fibroblasts) demonstrated that the
      mutated GGCX protein was larger, but its expression level and intracellular
      distribution were indistinguishable from those of the wild-type GGCX protein.
      Immunostaining and an enzyme-linked immunosorbent assay showed an increase in
      undercarboxylated matrix gamma-carboxyglutamic acid protein (ucMGP), a
      representative substrate of GGCX and a potent calcification inhibitor, indicating
      that mutated GGCX was enzymatically inactive. Under osteogenic conditions,
      calcium deposition was exclusively observed in GGCX dermal fibroblasts.
      Furthermore, GGCX dermal fibroblast cultures contained 23- and 7.7-fold more
      alkaline phosphatase (ALP)-positive cells than normal dermal fibroblast cultures
      (n = 3), without and with osteogenic induction, respectively. Expression and
      activity of ALP were higher in GGCX dermal fibroblasts than in normal dermal
      fibroblasts upon osteogenic induction. mRNA levels of other osteogenic markers
      were also higher in GGCX dermal fibroblasts than in normal dermal fibroblasts,
      which including bone morphogenetic protein 6, runt-related transcription factor
      2, and periostin (POSTN) without osteogenic induction; and osterix, collagen type
      I alpha 2, and POSTN with osteogenic induction. Together, these data indicate
      that GGCX dermal fibroblasts trans-differentiate into the osteogenic lineage.
      This study proposes another mechanism underlying aberrant calcification in
      patients with GGCX syndrome.

PMID- 28494011
TI  - Changes in the use practitioner-based complementary and alternative medicine over
      time in Canada: Cohort and period effects.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) is growing.
      However the factors contributing to changes over time and to birth cohort
      differences in CAM use are not well understood. SETTING: We used data from 10186
      participants, who were aged 20-69 years at the first cycle of data collection in
      the longitudinal component of the Canadian National Population Health Survey
      (1994/95-2010/11). We examined chiropractic and other practitioner-based CAM use
      with a focus on five birth cohorts: pre-World War II (born 1925-1934); World War
      II (born 1935-1944); older baby boomers (born 1945-1954); younger baby boomers
      (born 1955-1964); and Gen Xers (born 1965-1974). The survey collected data every
      two years on predisposing (e.g., sex, education), enabling (e.g., income),
      behavior-related factors (e.g., obesity), need (e.g., chronic conditions), and
      use of conventional care (primary care and specialists). RESULTS: The findings
      suggest that, at corresponding ages, more recent cohorts reported greater CAM (OR
      = 25.9, 95% CI: 20.0; 33.6 for Gen Xers vs. pre-World War) and chiropractic use
      than their predecessors (OR = 2.2, 95% CI: 1.7; 2.8 for Gen Xers vs. pre-World
      War). There was also a secular trend of increasing CAM use, but not chiropractic
      use, over time (period effect) across all ages. Factors associated with cohort
      differences were different for CAM and chiropractic use. Cohort differences in
      CAM use were partially related to a period effect of increasing CAM use over time
      across all ages while cohort differences in chiropractic use were related to the
      higher prevalence of chronic conditions among recent cohorts. The use of
      conventional care was positively related to greater CAM use (OR = 1.8, 95% CI:
      1.6; 2.0) and chiropractic use (OR = 1.2, 95% CI: 1.1; 1.4) but did not
      contribute to changes over time or to cohort differences in CAM and chiropractic
      use. CONCLUSION: The higher CAM use over time and in recent cohorts could reflect
      how recent generations are approaching their healthcare needs by expanding
      conventional care to include CAM therapies and practice for treatment and health
      promotion. The findings also underscore the importance of doctors discussing CAM
      use with their patients.

PMID- 28494012
TI  - Fabrication of malleable three-dimensional-printed customized bolus using three
      dimensional scanner.
AB  - A three-dimensional (3D)-printed customized bolus (3D bolus) can be used for
      radiotherapy application to irregular surfaces. However, bolus fabrication based
      on computed tomography (CT) scans is complicated and also delivers unwanted
      irradiation. Consequently, we fabricated a bolus using a 3D scanner and evaluated
      its efficacy. The head of an Alderson Rando phantom was scanned with a 3D
      scanner. The 3D surface data were exported and reconstructed with Geomagic Design
      X software. A 3D bolus of 5-mm thickness designed to fit onto the nose was
      printed with the use of rubber-like printing material, and a radiotherapy plan
      was developed. We successfully fabricated the customized 3D bolus, and further, a
      CT simulation indicated an acceptable fit of the 3D bolus to the nose. There was
      no air gap between the bolus and the phantom surface. The percent depth dose
      (PDD) curve of the phantom with the 3D bolus showed an enhanced surface dose when
      compared with that of the phantom without the bolus. The PDD of the 3D bolus was
      comparable with that of a commercial superflab bolus. The radiotherapy plan
      considering the 3D bolus showed improved target coverage when compared with that
      without the bolus. Thus, we successfully fabricated a customized 3D bolus for an
      irregular surface using a 3D scanner instead of a CT scanner.

PMID- 28494013
TI  - Modeling spatial variation in risk of presence and insecticide resistance for
      malaria vectors in Laos.
AB  - Climatic, sociological and environmental conditions are known to affect the
      spatial distribution of malaria vectors and disease transmission. Intensive use
      of insecticides in the agricultural and public health sectors exerts a strong
      selective pressure on resistance genes in malaria vectors. Spatio-temporal models
      of favorable conditions for Anopheles species' presence were developed to
      estimate the probability of presence of malaria vectors and insecticide
      resistance in Lao PDR. These models were based on environmental and
      meteorological conditions, and demographic factors. GIS software was used to
      build and manage a spatial database with data collected from various geographic
      information providers. GIS was also used to build and run the models. Results
      showed that potential insecticide use and therefore the probability of resistance
      to insecticide is greater in the southwestern part of the country, specifically
      in Champasack province and where malaria incidence is already known to be high.
      These findings can help national authorities to implement targeted and effective
      vector control strategies for malaria prevention and elimination among
      populations most at risk. Results can also be used to focus the insecticide
      resistance surveillance in Anopheles mosquito populations in more restricted
      area, reducing the area of surveys, and making the implementation of surveillance
      system for Anopheles mosquito insecticide resistance possible.

PMID- 28494014
TI  - Singularity: Scientific containers for mobility of compute.
AB  - Here we present Singularity, software developed to bring containers and
      reproducibility to scientific computing. Using Singularity containers, developers
      can work in reproducible environments of their choosing and design, and these
      complete environments can easily be copied and executed on other platforms.
      Singularity is an open source initiative that harnesses the expertise of system
      and software engineers and researchers alike, and integrates seamlessly into
      common workflows for both of these groups. As its primary use case, Singularity
      brings mobility of computing to both users and HPC centers, providing a secure
      means to capture and distribute software and compute environments. This ability
      to create and deploy reproducible environments across these centers, a previously
      unmet need, makes Singularity a game changing development for computational
      science.

PMID- 28494015
TI  - Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species
      production in macrophages.
AB  - Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized
      by insulin resistance and resulting hyperglycemia, which is associated with
      impaired wound healing. The clinical complications associated with hyperglycemia
      are attributed, in part, to the increased production of reactive oxygen species
      (ROS). Recent studies revealed that long non-coding RNAs (lncRNAs) play important
      regulatory roles in many biological processes. Specifically, lncRNA Lethe has
      been described as exhibiting an anti-inflammatory effect by binding to the p65
      subunit of NFkappaB and blocking its binding to DNA and the subsequent activation
      of downstream genes. We therefore hypothesize that dysregulation of Lethe's
      expression plays a role in hyperglycemia-induced ROS production. To test our
      hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM) or high
      glucose (25 mM) for 24h. High glucose conditions significantly induced ROS
      production and NOX2 gene expression in RAW cells, while significantly decreasing
      Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the
      increased ROS production induced by high glucose conditions, while also
      attenuating the upregulation of NOX2 expression. Similar results was found also
      in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage
      (BMM). Furthermore, overexpression of Lethe in RAW cells treated with high
      glucose significantly reduced the translocation of p65-NFkB to the nucleus, which
      resulted in decreased NOX2 expression and ROS production. Interestingly, these
      findings are consistent with the decreased Lethe gene expression and increased
      NOX2 gene expression observed in a mouse model of diabetic wound healing. These
      findings provide the first evidence that lncRNA Lethe is involved in the
      regulation of ROS production in macrophages through modulation of NOX2 gene
      expression via NFkappaB signaling. Moreover, this is the first report to describe
      a role of lncRNAs, in particular Lethe, in impaired diabetic wound healing.
      Further studies are warranted to determine if correction of Lethe expression in
      diabetic wounds could improve healing.

PMID- 28494016
TI  - The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human
      cytomegalovirus replication.
AB  - The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical
      drivers of virus replication and are considered pivotal in determining the
      balance between productive and latent infection. IE1 and IE2 are derived from the
      same primary transcript by alternative splicing and regulation of their
      expression likely involves a complex interplay between cellular and viral
      factors. Here we show that knockdown of the host ubiquitin-dependent segregase
      VCP/p97, results in loss of IE2 expression, subsequent suppression of early and
      late gene expression and, ultimately, failure in virus replication. RNAseq
      analysis showed increased levels of IE1 splicing, with a corresponding decrease
      in IE2 splicing following VCP knockdown. Global analysis of viral transcription
      showed the expression of a subset of viral genes is not reduced despite the loss
      of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies
      demonstrated that VCP strongly colocalised with the viral replication
      compartments in the nucleus. Finally, we show that NMS-873, a small molecule
      inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host
      targeting therapeutic for HCMV infection.

PMID- 28494017
TI  - Distinct cellular toxicity of two mutant huntingtin mRNA variants due to
      translation regulation.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat
      expansion within exon1 of the HTT gene. The gene generates two mRNA variants that
      carry either a short or long 3' untranslated region (3'UTR) while encoding the
      same protein. It remains unknown whether the two mRNA variants play distinct
      roles in HD pathogenesis. We found that the long HTT 3'UTR was capable of guiding
      mRNA to neuronal dendrites, suggesting that some long-form HTT mRNA is
      transported to dendrites for local protein synthesis. To assay roles of two HTT
      mRNA variants in cell bodies, we expressed mRNA harboring HTT exon1 containing
      23x or 145x CAGs with the short or long 3'UTR. We found that mutant mRNA
      containing the short 3'UTR produced more protein aggregates and caused more
      apoptosis in both cultured neurons and HEK293 cells, compared with mutant mRNA
      containing the long 3'UTR. Although the two 3'UTRs did not affect mRNA stability,
      we detected higher levels of protein synthesis from mRNA containing the short
      3'UTR than from mRNA containing the long 3'UTR. These results indicate that the
      long HTT 3'UTR suppresses translation. Thus, short-form mutant HTT mRNA will be
      more efficient in producing toxic protein than its long-form counterpart.

PMID- 28494018
TI  - Pathogenic outcome following experimental infection of sheep with Chlamydia
      abortus variant strains LLG and POS.
AB  - This study investigated the pathogenesis of two variant strains (LLG and POS) of
      Chlamydia abortus, in comparison to a typical wild-type strain (S26/3) which is
      known to be responsible for late term abortion in small ruminants. Challenge with
      the three strains at mid-gestation resulted in similar pregnancy outcomes, with
      abortion occurring in approximately 50-60% of ewes with the mean gestational
      lengths also being similar. However, differences were observed in the severity of
      placental pathology, with infection appearing milder for strain LLG, which was
      reflected in the lower number of organisms shed in vaginal swabs post-partum and
      less gross pathology and organisms present in placental smears. Results for
      strain POS were somewhat different than LLG with a more focal restriction of
      infection observed. Post-abortion antibody responses revealed prominent
      differences in seropositivity to the major outer membrane protein (MOMP) present
      in elementary body (EB) preparations under denaturing conditions, most notably
      with anti-LLG and anti-POS convalescent sera where there was no or reduced
      detection of MOMP present in EBs derived from the three strains. These results
      and additional analysis of whole EB and chlamydial outer membrane complex
      preparations suggest that there are conformational differences in MOMP for the
      three strains. Overall, the results suggest that gross placental pathology and
      clinical outcome is not indicative of bacterial colonization and the severity of
      infection. The results also highlight potential conformational differences in
      MOMP epitopes that perhaps impact on disease diagnosis and the development of new
      vaccines.

PMID- 28494019
TI  - The issue of plasma asymmetric dimethylarginine reference range - A systematic
      review and meta-analysis.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
      nitric oxide synthase, marker and mediator of endothelial dysfunction. Several
      studies have demonstrated its value in cardiovascular risk stratification and all
      cause mortality prediction. The aim was to determine the reference range of
      plasma ADMA in healthy adults. METHODS AND RESULTS: Taking into account the most
      widely used ADMA measurement methods, only studies using either high performance
      liquid chromatography (HPLC) -with fluorescence or mass spectrometric detection-,
      or enzyme-linked immunosorbent assay (ELISA) to quantify plasma ADMA
      concentrations were enrolled. 66 studies were included in the quantitative
      analysis (24 using ELISA and 42 using HPLC) reporting a total number of 5528 non
      diabetic, non-hypertensive, non-obese adults without any medication (3178 men and
      2350 women, 41.6 +/- 16.9 years old). The reference range of ADMA (in MUmol/l
      with 95% confidence interval in parenthesis) was 0.34 (0.29-0.38)- 1.10 (0.85
      1.35) with a mean of 0.71 (0.57-0.85) (n = 4093) measured by HPLC and 0.25 (0.18
      0.31)- 0.92 (0.76-1.09) with a mean of 0.57 (0.48-0.66) (n = 1435) by ELISA.
      CONCLUSIONS: Numerous publications suggested that asymmetric dimethylarginine is
      not only an outstanding tool of disease outcome prediction but also a new
      potential therapeutic target substance; the reference range provided by this meta
      analysis can become of great importance and aid to further investigations.
      However, developing a standard measurement method would be beneficial to
      facilitate the clinical usage of ADMA.

PMID- 28494020
TI  - Pannexin 3 regulates proliferation and differentiation of odontoblasts via its
      hemichannel activities.
AB  - Highly coordinated regulation of cell proliferation and differentiation
      contributes to the formation of functionally shaped and sized teeth; however, the
      mechanism underlying the switch from cell cycle exit to cell differentiation
      during odontogenesis is poorly understood. Recently, we identified pannexin 3
      (Panx3) as a member of the pannexin gap junction protein family from tooth germs.
      The expression of Panx3 was predominately localized in preodontoblasts that arise
      from dental papilla cells and can differentiate into dentin-secreting
      odontoblasts. Panx3 also co-localized with p21, a cyclin-dependent kinase
      inhibitor protein, in preodontoblasts. Panx3 was expressed in primary dental
      mesenchymal cells and in the mDP dental mesenchymal cell line. Both Panx3 and p21
      were induced during the differentiation of mDP cells. Overexpression of Panx3 in
      mDP cells reduced cell proliferation via up-regulation of p21, but not of p27,
      and promoted the Bone morphogenetic protein 2 (BMP2)-induced phosphorylation of
      Smad1/5/8 and the expression of dentin sialophosphoprotein (Dspp), a marker of
      differentiated odontoblasts. Furthermore, Panx3 released intracellular ATP into
      the extracellular space through its hemichannel and induced the phosphorylation
      of AMP-activated protein kinase (AMPK). 5-Aminoimidazole-4-carboxamide
      ribonucleoside (AICAR), an activator of AMPK, reduced mDP cell proliferation and
      induced p21 expression. Conversely, knockdown of endogenous Panx3 by siRNA
      inhibited AMPK phosphorylation, p21 expression, and the phosphorylation of
      Smad1/5/8 even in the presence of BMP2. Taken together, our results suggest that
      Panx3 modulates intracellular ATP levels, resulting in the inhibition of
      odontoblast proliferation through the AMPK/p21 signaling pathway and promotion of
      cell differentiation by the BMP/Smad signaling pathway.

PMID- 28494021
TI  - Rice black streaked dwarf virus P7-2 forms a SCF complex through binding to Oryza
      sativa SKP1-like proteins, and interacts with GID2 involved in the gibberellin
      pathway.
AB  - As a core subunit of the SCF complex that promotes protein degradation through
      the 26S proteasome, S-phase kinase-associated protein 1 (SKP1) plays important
      roles in multiple cellular processes in eukaryotes, including gibberellin (GA),
      jasmonate, ethylene, auxin and light responses. P7-2 encoded by Rice black
      streaked dwarf virus (RBSDV), a devastating viral pathogen that causes severe
      symptoms in infected plants, interacts with SKP1 from different plants. However,
      whether RBSDV P7-2 forms a SCF complex and targets host proteins is poorly
      understood. In this study, we conducted yeast two-hybrid assays to further
      explore the interactions between P7-2 and 25 type I Oryza sativa SKP1-like (OSK)
      proteins, and found that P7-2 interacted with eight OSK members with different
      binding affinity. Co-immunoprecipitation assay further confirmed the interaction
      of P7-2 with OSK1, OSK5 and OSK20. It was also shown that P7-2, together with
      OSK1 and O. sativa Cullin-1, was able to form the SCF complex. Moreover, yeast
      two-hybrid assays revealed that P7-2 interacted with gibberellin insensitive
      dwarf2 (GID2) from rice and maize plants, which is essential for regulating the
      GA signaling pathway. It was further demonstrated that the N-terminal region of
      P7-2 was necessary for the interaction with GID2. Overall, these results
      indicated that P7-2 functioned as a component of the SCF complex in rice, and
      interaction of P7-2 with GID2 implied possible roles of the GA signaling pathway
      during RBSDV infection.

PMID- 28494022
TI  - The effect of biological sealants and adhesive treatments on matrix
      metalloproteinase expression during renal injury healing.
AB  - BACKGROUND: Renal injuries are relatively common in cases of abdominal trauma.
      Adhesives and sealants can be used to repair and preserve damaged organs. Using a
      rat model, this study explores the activity of different matrix
      metalloproteinases (MMP) during the healing of renal injuries treated by two
      biological adhesives (TachoSil and GelitaSpon) and a new synthetic elastic
      cyanoacrylate (Adhflex). METHODS: Renal traumatic injuries were experimentally
      induced in 90 male Wistar rats by a Stiefel Biopsy Punch in the anterior aspect
      of the left kidney. Animals were divided into five groups: 1, sham non-injured (n
      = 3); 2, non-treated standard punch injury (n = 6); 3, punch injury treated with
      TachoSil (n = 27); 4, punch injury treated with GelitaSpon (n = 27); and, 5,
      punch injury treated with Adhflex (n = 27). Wound healing was evaluated 2, 6, and
      18 days after injury by determining the expression of MMPs, and the
      histopathological evolution of lesions. FINDINGS: Histologically, the wound size
      at 6 days post-injury was larger in Adhflex-treated samples than in the other
      treatments, but the scarring tissue was similar at 18 days post-injury. Only the
      MMPs subtypes 1, 2, 8, 9, and 13 were sufficiently expressed to be quantifiable.
      Both time since injury and treatment type had a significant influence on MMPs
      expression. Two days after injury, the expression of MMP8 and MMP9 was
      predominant. MMP2 expression was greater 6 days after injury. The Adhflex-treated
      group had a significantly higher MMPs expression than the other treatment groups
      at all healing stages. CONCLUSIONS: All three sealant treatments induced almost
      similar expression of MMPs than untreated animals indicating a physiological
      healing process. Given that all renal trauma injuries must be considered
      emergencies, both biological and synthetic adhesives, such as Adhflex, should be
      considered as a treatment options.

PMID- 28494023
TI  - Your move: The effect of chess on mathematics test scores.
AB  - We analyse the effect of substituting a weekly mathematics lesson in primary
      school grades 1-3 with a lesson in mathematics based on chess instruction. We use
      data from the City of Aarhus in Denmark, combining test score data with a
      comprehensive data set obtained from administrative registers. We use two
      different methodological approaches to identify and estimate treatment effects
      and we tend to find positive effects, indicating that knowledge acquired through
      chess play can be transferred to the domain of mathematics. We also find larger
      impacts for unhappy children and children who are bored in school, perhaps
      because chess instruction facilitates learning by providing an alternative
      approach to mathematics for these children. The results are encouraging and
      suggest that chess may be an important and effective tool for improving
      mathematical capacity in young students.

PMID- 28494024
TI  - Household food security and adequacy of child diet in the food insecure region
      north in Ghana.
AB  - BACKGROUND AND OBJECTIVES: Adequate diet is of crucial importance for healthy
      child development. In food insecure areas of the world, the provision of adequate
      child diet is threatened in the many households that sometimes experience having
      no food at all to eat (household food insecurity). In the context of food
      insecure northern Ghana, this study investigated the relationship between level
      of household food security and achievement of recommended child diet as measured
      by WHO Infant and Young Child Feeding Indicators. METHODS: Using data from
      households and 6-23 month old children in the 2012 Feed the Future baseline
      survey (n = 871), descriptive analyses assessed the prevalence of minimum meal
      frequency; minimum dietary diversity, and minimum acceptable diet. Logistic
      regression analysis was used to examine the association of minimum acceptable
      diet with household food security, while accounting for the effects of child sex
      and age, maternal -age, -dietary diversity, -literacy and -education, household
      size, region, and urban-rural setting. Household food security was assessed with
      the Household Hunger Scale developed by USAID's Food and Nutrition Technical
      Assistance Project. RESULTS: Forty-nine percent of children received minimum
      recommended meal frequency, 31% received minimum dietary diversity, and 17% of
      the children received minimum acceptable diet. Sixty-four percent of the children
      lived in food secure households, and they were significantly more likely than
      children in food insecure households to receive recommended minimum acceptable
      diet [O.R = 0.53; 95% CI: 0.35, 0.82]. However, in 80% of food secure households,
      children did not receive a minimal acceptable diet by WHO standards. CONCLUSIONS:
      Children living in food secure households were more likely than others to receive
      a minimum acceptable diet. Yet living in a food secure household was no guarantee
      of child dietary adequacy, since eight of 10 children in food secure households
      received less than a minimum acceptable diet. The results call for research into
      factors besides household food security in the search for determinants of child
      diet adequacy. In this study at least, household food security was a very weak
      marker of child diet adequacy. This finding is of significance to public health
      practice, since it calls into question any assumption that having enough food in
      a household necessarily results in adequately fed children.

PMID- 28494026
TI  - Correction: Role of Interleukin-10 on Nasal Polypogenesis in Patients with
      Chronic Rhinosinusitis with Nasal Polyps.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0161013.].

PMID- 28494025
TI  - Sequencing of small RNAs of the fern Pleopeltis minima (Polypodiaceae) offers
      insight into the evolution of the microrna repertoire in land plants.
AB  - MicroRNAs (miRNAs) are short, single stranded RNA molecules that regulate the
      stability and translation of messenger RNAs in diverse eukaryotic groups. Several
      miRNA genes are of ancient origin and have been maintained in the genomes of
      animal and plant taxa for hundreds of millions of years, playing key roles in
      development and physiology. In the last decade, genome and small RNA (sRNA)
      sequencing of several plant species have helped unveil the evolutionary history
      of land plants. Among these, the fern group (monilophytes) occupies a key
      phylogenetic position, as it represents the closest extant cousin taxon of seed
      plants, i.e. gymno- and angiosperms. However, in spite of their evolutionary,
      economic and ecological importance, no fern genome has been sequenced yet and few
      genomic resources are available for this group. Here, we sequenced the small RNA
      fraction of an epiphytic South American fern, Pleopeltis minima (Polypodiaceae),
      and compared it to plant miRNA databases, allowing for the identification of
      miRNA families that are shared by all land plants, shared by all vascular plants
      (tracheophytes) or shared by euphyllophytes (ferns and seed plants) only. Using
      the recently described transcriptome of another fern, Lygodium japonicum, we also
      estimated the degree of conservation of fern miRNA targets in relation to other
      plant groups. Our results pinpoint the origin of several miRNA families in the
      land plant evolutionary tree with more precision and are a resource for future
      genomic and functional studies of fern miRNAs.

PMID- 28494027
TI  - No evidence of genome editing activity from Natronobacterium gregoryi Argonaute
      (NgAgo) in human cells.
AB  - The argonaute protein from the thermophilic bacterium Thermus thermophilus shows
      DNA-guided DNA interfering activity at high temperatures, complicating its
      application in mammalian cells. A recent work reported that the argonaute protein
      from Natronobacterium gregoryi (NgAgo) had DNA-guided genome editing activity in
      mammalian cells. We compared the genome editing activities of NgAgo and
      Staphylococcus aureus Cas9 (SaCas9) in human HEK293T cells side by side. EGFP
      reporter assays and DNA sequencing consistently revealed high genome editing
      activity from SaCas9. However, these assays did not demonstrate genome editing
      activity by NgAgo. We confirmed that the conditions allowed simultaneous
      transfection of the NgAgo expressing plasmid DNA and DNA guides, as well as
      heterologous expression of NgAgo in the HEK293T cells. Our data show that NgAgo
      is not a robust genome editing tool, although it may have such activity under
      other conditions.

PMID- 28494028
TI  - Rosemary supplementation (Rosmarinus oficinallis L.) attenuates cardiac
      remodeling after myocardial infarction in rats.
AB  - BACKGROUND: Myocardial infarction (MI) is one of the leading causes of morbidity
      and mortality worldwide. Dietary intervention on adverse cardiac remodeling after
      MI has significant clinical relevance. Rosemary leaves are a natural product with
      antioxidant/anti-inflammatory properties, but its effect on morphology and
      ventricular function after MI is unknown. METHODS AND RESULTS: To determine the
      effect of the dietary supplementation of rosemary leaves on cardiac remodeling
      after MI, male Wistar rats were divided into 6 groups after sham procedure or
      experimental induced MI: 1) Sham group fed standard chow (SR0, n = 23); 2) Sham
      group fed standard chow supplemented with 0.02% rosemary (R002) (SR002, n = 23);
      3) Sham group fed standard chow supplemented with 0.2% rosemary (R02) (SR02, n =
      22); 4) group submitted to MI and fed standard chow (IR0, n = 13); 5) group
      submitted to MI and fed standard chow supplemented with R002 (IR002, n = 8); and
      6) group submitted to MI and fed standard chow supplemented with R02 (IR02, n =
      9). After 3 months of the treatment, systolic pressure evaluation,
      echocardiography and euthanasia were performed. Left ventricular samples were
      evaluated for: fibrosis, cytokine levels, apoptosis, energy metabolism enzymes,
      and oxidative stress. Rosemary dietary supplementation attenuated cardiac
      remodeling by improving energy metabolism and decreasing oxidative stress.
      Rosemary supplementation of 0.02% improved diastolic function and reduced
      hypertrophy after MI. Regarding rosemary dose, 0.02% and 0.2% for rats are
      equivalent to 11 mg and 110 mg for humans, respectively. CONCLUSION: Our findings
      support further investigations of the rosemary use as adjuvant therapy in adverse
      cardiac remodeling.

PMID- 28494030
TI  - Antibody-nanoparticle conjugates to enhance the sensitivity of ELISA-based
      detection methods.
AB  - Accurate antigen detection is imperative for clinicians to diagnose disease,
      assess treatment success, and predict patient prognosis. The most common
      technique used for the detection of disease-associated biomarkers is the enzyme
      linked immunosorbent assay (ELISA). In an ELISA, primary antibodies are incubated
      with biological samples containing the biomarker of interest. Then, detectible
      secondary antibodies conjugated with horseradish peroxidase (HRP) bind the
      primary antibodies. Upon addition of a color-changing substrate, the samples
      provide a colorimetric signal that directly correlates to the targeted biomarker
      concentration. While ELISAs are effective for analyzing samples with high
      biomarker content, they lack the sensitivity required to analyze samples with low
      antigen levels. We hypothesized that the sensitivity of ELISAs could be enhanced
      by replacing freely delivered primary antibodies with antibody-nanoparticle
      conjugates that provide excess binding sites for detectible secondary antibodies,
      ultimately leading to increased signal. Here, we investigated the use of
      nanoshells (NS) decorated with antibodies specific to epidermal growth factor
      receptor (EGFR) as a model system (EGFR-NS). We incubated one healthy and two
      breast cancer cell lines, each expressing different levels of EGFR, with EGFR-NS,
      untargeted NS, or unconjugated EGFR antibodies, as well as detectable secondary
      antibodies. We found that EGFR-NS consistently increased signal intensity
      relative to unconjugated EGFR antibodies, with a substantial 13-fold enhancement
      from cells expressing high levels of EGFR. Additionally, 40x more unconjugated
      antibodies were required to detect EGFR compared to those conjugated to NS. Our
      results demonstrate that antibody-nanoparticle conjugates lower the detection
      limit of traditional ELISAs and support further investigation of this strategy
      with other antibodies and nanoparticles. Owing to their enhanced sensitivity, we
      anticipate that nanoparticle-modified ELISAs can be used to detect low levels of
      biomarkers found in various diseases, such as cancers, tuberculosis, and
      rheumatoid arthritis, and may ultimately enable earlier diagnosis, better
      prognostication, and improved treatment monitoring.

PMID- 28494029
TI  - Characterization of miR-122-independent propagation of HCV.
AB  - miR-122, a liver-specific microRNA, is one of the determinants for liver tropism
      of hepatitis C virus (HCV) infection. Although miR-122 is required for efficient
      propagation of HCV, we have previously shown that HCV replicates at a low rate in
      miR-122-deficient cells, suggesting that HCV-RNA is capable of propagating in an
      miR-122-independent manner. We herein investigated the roles of miR-122 in both
      the replication of HCV-RNA and the production of infectious particles by using
      miR-122-knockout Huh7 (Huh7-122KO) cells. A slight increase of intracellular HCV
      RNA levels and infectious titers in the culture supernatants was observed in Huh7
      122KO cells upon infection with HCV. Moreover, after serial passages of HCV in
      miR-122-knockout Huh7.5.1 cells, we obtained an adaptive mutant, HCV122KO,
      possessing G28A substitution in the 5'UTR of the HCV genotype 2a JFH1 genome, and
      this mutant may help to enhance replication complex formation, a possibility
      supported by polysome analysis. We also found the introduction of adaptive
      mutation around miR-122 binding site in the genotype 1b/2a chimeric virus, which
      originally had an adenine at the nucleotide position 29. HCV122KO exhibited
      efficient RNA replication in miR-122-knockout cells and non-hepatic cells without
      exogenous expression of miR-122. Competition assay revealed that the G28A mutant
      was dominant in the absence of miR-122, but its effects were equivalent to those
      of the wild type in the presence of miR-122, suggesting that the G28A mutation
      does not confer an advantage for propagation in miR-122-rich hepatocytes. These
      observations may explain the clinical finding that the positive rate of G28A
      mutation was higher in miR-122-deficient PBMCs than in the patient serum, which
      mainly included the hepatocyte-derived virus from HCV-genotype-2a patients. These
      results suggest that the emergence of HCV mutants that can propagate in non
      hepatic cells in an miR-122-independent manner may participate in the induction
      of extrahepatic manifestations in chronic hepatitis C patients.

PMID- 28494031
TI  - Evaluation of Pink and White Esthetic Scores for Immediately Placed and
      Provisionally Restored Implants in the Anterior Maxilla.
AB  - PURPOSE: To evaluate the esthetic result of immediately placed implants with
      immediate provisional restorations in the anterior maxilla using the pink
      esthetic score (PES) and white esthetic score (WES). MATERIALS AND METHODS: The
      records of patients were evaluated retrospectively. The evaluation was carried
      out by two examiners using 12 evaluation criteria. RESULTS: The average PES value
      from the evaluation of 53 images obtained from the 53 selected patients (22 men
      and 31 women) was 8.63 +/- 2.4 (range, 1-14), whereas the average WES value was
      6.92 +/- 1.67 (range, 2-10). The mesial papilla had the highest average PES (1.39
      +/- 0.4) and the distal papilla had the lowest PES (0.87 +/- 0.54). Texture had
      the highest average WES (1.54 +/- 0.34) and tooth shape had the lowest average
      WES (1.25 +/- 0.43). CONCLUSION: Treatment with immediate implants providing
      immediate provisional restoration in the anterior maxilla yields good clinical
      esthetic outcomes, as assessed by PES/WES values. The PES and WES values showed
      strong intraexaminer agreement, but weak interexaminer agreement.

PMID- 28494032
TI  - Radiographic Appearance of Interocclusal Record Materials for Cone Beam Computed
      Tomography-Guided Implant Surgeries.
AB  - PURPOSE: To select an ideal interocclusal record material for cone beam computed
      tomography (CBCT)-guided implant surgery based on the material's radiodensity on
      the scan. MATERIALS AND METHODS: Twelve commonly used interocclusal record
      materials were used for this investigation: two were waxes, one was polyether,
      and nine were polyvinyl-siloxane-type materials. A scan template was fabricated
      by duplicating existing dentures in Ortho-Jet acrylic resin mixed with 30% barium
      powder for the teeth and 10% barium powder for the denture base between the teeth
      and the tissue. An interocclusal record was fabricated with each material, and
      the same template was used to obtain a CBCT scan with an ICAT machine (Imaging
      Sciences International) at 0.3 voxel and 14-bit depth settings. Twelve CBCT scans
      were obtained and analyzed. The radiopacity of the barium teeth was used as a
      control and was compared with the opacity of the 12 materials using a paired t
      test. A post hoc analysis of variance (ANOVA) test was used to compare the
      densities of the various materials with each other. RESULTS: There was a
      statistically significant difference between the radiopacity of barium teeth
      (gray value: 1,959.475) and that of Modelling Wax (gray value: 750; P = .0026),
      Aluwax (gray value: 795.22; P = .0022), Blu-Bite CT (gray value: 1,105; P =
      .005), Ramitec (gray value: 1,105.3; P = .08), Memosil 2 (gray value: 1,202; P =
      .01) followed by Reprosil (gray value: 1,407.73; P = .01). Compared with the
      barium teeth, there was no statistically significant difference between the
      densities of Futar D (gray value: 1,866.5; P = .51), Jet Bite (gray value:
      1,660.04; P = .08), Lab-Putty (gray value: 1,402.14; P = .19), and Memoreg 2
      (gray value: 1,754.72; P = .1). The highest radiodensity was seen with Blu-Mousse
      (gray value: 2,949; P = .007) and Take 1 (gray value: 2,229.85; P = .025), which
      were also significantly different from the density of the barium teeth but in the
      opposite direction, making them more opaque. CONCLUSION: Within the limitations
      of this in vitro study, the most radiolucent appearance of Modelling Wax, Aluwax,
      Memosil 2, Blu-Bite CT, and Ramitec made them the suitable materials of choice of
      those tested, as the interocclusal registration record during CBCT scanning
      allowed clear visualization of barium teeth.

PMID- 28494033
TI  - Intraoperative Complications During Sinus Floor Elevation with Lateral Approach:
      A Systematic Review.
AB  - PURPOSE: To analyze the occurrence of intraoperative complications during sinus
      floor elevation with a lateral approach and their correlations with the technique
      adopted by surgeons. MATERIALS AND METHODS: Electronic and manual searches
      resulted in 4,417 records on sinus floor elevation. Twenty-one randomized
      clinical trials (RCTs) and 11 prospective controlled clinical trials (CCTs)
      reporting occurrence of intraoperative complications were included. Risk of bias
      was assessed according to the Cochrane tool and a modified Downs and Black
      quality analysis for RCTs and CCTs, respectively. RESULTS: Sinus membrane
      perforation and hemorrhagic events following vascular lesions were the only
      intraoperative complications reported by the selected studies with overall
      occurrences of 15.7% and 0.4%, respectively. Three different surgical devices
      (rotary instruments, piezoelectric osteotomes, and manual bone scrapers) were
      used to perform the lateral antrostomy. Ultrasonic devices and bone scrapers
      showed a lower incidence (10.9% and 6.0%, respectively) of membrane perforation
      compared with that of rotary instruments (20.1%). Among the different ultrasonic
      procedures, erosion of the lateral antral wall showed the lowest membrane
      perforations (4.7% incidence). Hemorrhagic complications seemed to be extremely
      infrequent with any surgical technique. CONCLUSION: Sinus membrane perforation
      was the most frequently described intraoperative complication during sinus floor
      elevation with a lateral approach. Thinning the lateral wall of the sinus before
      performing the antrostomy (either with ultrasonic devices or manual bone
      scrapers) seemed to be an important factor in preventing membrane perforation
      during sinus surgery. Further high-quality RCTs specifically investigating
      intraoperative complication occurrence are needed.

PMID- 28494034
TI  - Efficacy of Local and Systemic Statin Delivery on the Osseointegration of
      Implants: A Systematic Review.
AB  - PURPOSE: In indexed literature, a systematic review of the efficacy of statins in
      enhancing osseointegration is lacking. The aim of this systematic review was to
      assess the efficacy of local and systemic statin delivery on the osseointegration
      of implants. MATERIALS AND METHODS: To address the focused question, "Does local
      and systemic statin delivery affect osseointegration around implants?", indexed
      databases were searched from 1965 through November 2015 using various keywords.
      Letters to the Editor, case reports/case series, historic reviews, and
      commentaries were excluded. The pattern of this systematic review was customized
      to primarily summarize the pertinent data. RESULTS: Nineteen studies were
      included. All studies were experimental and were performed in animal models. In
      seven studies, statins were delivered systemically via oral, intraperitoneal,
      intraosseous, subcutaneous, and percutaneous routes. Among the 12 studies, where
      statins were delivered locally, statin-coated implants were used in seven
      studies, whereas in the remaining studies, statins were delivered via topical
      application on the bone cavities. The follow-up duration ranged between 1 and 12
      weeks. Results from 18 studies showed that statin administration enhanced new
      bone formation (NBF) around implants and/or bone-to-implant contact. One study
      showed that statin-coated implant surfaces impaired osseointegration. Seven
      studies reported that statin administration enhanced NBF around implants in
      osteoporotic rats. CONCLUSION: On experimental grounds, local and systemic statin
      delivery seems to enhance osseointegration; however, from a clinical perspective,
      further studies are needed to assess the role of statins in promoting
      osseointegration around dental implants.

PMID- 28494035
TI  - An In Vitro Model to Evaluate the Accuracy of Guided Implant Placement Based on
      the Surgeon's Experience.
AB  - PURPOSE: To evaluate whether there are differences in the accuracy of guided
      implant placement based on the surgeon's experience level. MATERIALS AND METHODS:
      Fifteen surgeons, divided into three groups based on experience level (group I,
      expert; group II, intermediate; group III, novice), placed six implants in five
      identical mandibles (75 mandibles and 450 implants). A planning and
      stereolithographic guide was generated using cone beam computed tomography (CBCT)
      images and implant planning software (Nemoscan, Nemotec) and was used in all
      cases. After the implants were placed in each mandible, another scan was taken,
      and the three-dimensional (3D) images of each scan were blended with the images
      in the planning guide to evaluate any deviations. Any differences in platform and
      apex position and the angle of the implant were measured. The differences between
      each surgeon and each group were compared using multivariate analysis of variance
      (MANOVA). RESULTS: There were significant differences in the implant angles among
      the three groups (P = .001). Group III (novices) presented the greatest angle
      deviation and showed more deviations than group I (experts) (P = .024) and group
      II (intermediate) (P = .001) did. There were no significant differences between
      groups I and II (P = .368). There were no significant differences among the
      groups in terms of platform (P = .135) and apex position (P = .092). CONCLUSION:
      Some degree of deviation can occur between the planned placement of the implant
      and its definitive placement, and this deviation may be influenced by the
      surgeon's experience. Expert surgeons show less angle deviation than novice
      surgeons. Although these differences (less than 0.5 degrees) are statistically
      significant, they may be considered clinically irrelevant.

PMID- 28494036
TI  - Epidemiology of Implant Mortality Disparity Among Intraoral Positions and
      Prosthesis Types.
AB  - PURPOSE: To examine the disparity of single-crown implant failure with a similar
      loss of the splinted prosthesis in differing anatomical locations while
      controlling for other demographic and clinical variables that may confound the
      relationship between prosthesis types and implant loss. MATERIALS AND METHODS: A
      multicenter retrospective cohort study was designed to include patients treated
      with dental implants from 2003 to 2014. The variables included age, sex, systemic
      disease, bone graft, implant placement date, position of dental implant, length
      of dental implant, diameter of dental implant, loading time, type of prosthesis,
      type of opposing occlusion, latest check date, and survival or loss of the dental
      implant. The demographic and clinical variables' influence on the survival of
      dental implants was estimated by the Kaplan-Meier method. The position and
      diameter were adjusted for the accurate estimation of the relationship between
      the prosthesis type and survival of the dental implant with the Cox proportional
      hazard method. RESULTS: A total of 1,151 dental implants from 403 patients were
      ascertained. After adjusting for the confounding effect of position and diameter,
      single-crown prostheses were 38.1 (95% CI: 15.1-118) times more likely to be lost
      than the connected-type prostheses. For single-crown implants, the waiting time
      for osseointegration before loading was the highest for the maxillary molar
      position and the lowest for the mandibular molar position (P < .0001), while the
      most frequent implant loss occurred in the maxillary anterior area, and the
      second frequent area was the maxillary molar position; the lowest occurrence of
      implant loss was for the mandibular molar position. This disparity was
      statistically significant (P = .0271). CONCLUSION: Despite the high survival
      rates of endosseous implants as a whole, since the variation of implant loss was
      observed among the different anatomical positions for single-crown implants,
      special attention has to be given to the maxillary anterior and maxillary molar
      positions. A longer healing time assuming compensation for disadvantageous bone
      quality was not directly effective in increasing implant longevity in the
      vulnerable positions.

PMID- 28494037
TI  - Effect of Abutment Preparation and Fatigue Loading in a Moist Environment on the
      Fracture Resistance of the One-Piece Zirconia Dental Implant.
AB  - PURPOSE: One-piece zirconia dental implants have been widely used in Europe for
      many years. This in vitro study was done to evaluate the effect of abutment
      preparation and fatigue (cyclic) loading in a moist environment on the fracture
      resistance of the one-piece zirconia dental implant. MATERIALS AND METHODS:
      Twenty-four Cera Root zirconium oxide dental implants, divided into three groups
      of eight, were used in this study: group 1 (control group): implants with no
      preparation, tested in a dry environment; group 2: implants with no preparation,
      tested in a moist environment (simulating clinical conditions); and group 3:
      implants after abutment preparation tested in a moist environment. All implants
      received IPS e.max porcelain crowns. All samples were subjected to nearly 1
      million cycles of sinusoidal fatigue loading (-10 N to -200 N) in a universal
      testing machine. The postfatigue samples were loaded to fracture. Significant
      differences (alpha = .05) in mean fracture loads were statistically analyzed.
      RESULTS: There was no catastrophic failure of any of the implants during the
      fatigue tests. The mean (SD) of the fracture loads in postfatigue load-to-failure
      tests were: group 1: 1,202.9 (62.6); group 2: 1,164.6 (73.8); and group 3: 953.5
      (103). Analysis of variance (ANOVA) and post hoc Tukey-Kramer contrast revealed a
      statistically significant difference (P < .05) between the mean fracture load of
      group 3 and those of groups 1 and 2, but no significant difference (P > .05)
      between groups 1 and 2. CONCLUSION: While there was a statistically significant
      adverse effect of abutment preparation and fatigue loading in a moist environment
      on the postfatigue implant failure load, the load-to-fracture mean of surface
      prepared implants after fatigue tests was nevertheless significantly higher than
      the mean fracture load of the crowns (P < .05) as well as the minimum load
      bearing requirement (300 N) for anterior restorations. Abutment preparation in a
      one-piece zirconia implant is therefore considered clinically safe and
      acceptable.

PMID- 28494038
TI  - Role of Metformin in Reversing the Negative Impact of Hyperglycemia on Bone
      Healing Around Implants Inserted in Type 2 Diabetic Rats.
AB  - PURPOSE: There is interest in establishing hypoglycemiant agents able to
      contain/revert the impact of diabetes mellitus on osseointegration. The purpose
      of this study was to assess the possible effect of metformin in reversing the
      negative effects of hyperglycemia on the healing of bone surrounding implants
      inserted in rats. MATERIALS AND METHODS: Rats (10 per group) were assigned to one
      of the following groups: DM group: type 2 diabetic rats deprived of metformin (M)
      treatment; MDM group: type 2 diabetic rats under M treatment (40 mg/kg/day,
      starting on the 15th day after implant placement); control group: nondiabetic
      rats without M treatment. At 30 days after streptozotocin injection, titanium
      implants were placed in tibiae. Animals were euthanized 30 days after implant
      surgery. Bone-to-implant contact (BIC), bone area (BA), and the number of
      receptor activator of nuclear factor kappaB ligand (RANKL)- and osteoprotegerin
      (OPG)-stained cells were assessed in cortical and medullary areas. RESULTS: The
      percentages of BIC and BA in the cortical bone were reduced in the DM and MDM
      groups compared with the control group (P < .05). The percentage of BA in the
      medullary region was reduced in the DM group compared with the control group (P <
      .05). The MDM group showed the greatest number of OPG-stained cells, while the DM
      group presented the greatest ratio of RANKL/OPG in the medullary area (P < .05).
      CONCLUSION: Metformin did not modulate the damaging effect of hyperglycemia on
      bone healing around implants at histometric levels, but increased the expression
      of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some
      molecular benefits in the osseointegration of implants under the hyperglycemic
      state.

PMID- 28494039
TI  - Top-Cited Articles in Implant Dentistry.
AB  - PURPOSE: Citation analysis is the field of bibliometrics that uses citation data
      to evaluate the scientific recognition and the influential performance of a
      research article in the scientific community. The aim of this study was to
      conduct a bibliometric analysis of the top-cited articles pertaining to implant
      dentistry, to analyze the main characteristics, and to display the most
      interesting topics and evolutionary trends. MATERIALS AND METHODS: The 100 top
      cited articles published in "Dentistry, Oral Surgery, and Medicine" journals were
      identified using the Science Citation Index Database. The articles were further
      reviewed, and basic information was collected, including the number of citations,
      journals, authors, publication year, study design, level of evidence, and field
      of study. RESULTS: The highly cited articles in implant dentistry were cited
      between 199 and 2,229 times. The majority of them were published in four major
      journals: Clinical Oral Implants Research, International Journal of Oral &
      Maxillofacial Implants, Journal of Clinical Periodontology, and Journal of
      Periodontology. The publication year ranged from 1981 to 2009, with 45% published
      in a nine-year period (2001 to 2009). Publications from the United States (29%)
      were the most heavily cited, followed by those from Sweden (23%) and Switzerland
      (17%). The University of Goteborg from Sweden produced the highest number of
      publications (n = 19), followed by the University of Bern in Switzerland (n =
      13). There was a predominance of clinical papers (n = 42), followed by reviews (n
      = 25), basic science research (n = 21), and proceedings papers (n = 12). Peri
      implant tissue healing and health (24%), implant success/failures (19.2%), and
      biomechanical topics (16.8%) were the most common fields of study. CONCLUSION:
      Citation analysis in the field of implant dentistry reveals interesting
      information about the topics and trends negotiated by researchers and elucidates
      which characteristics are required for a paper to attain a "classic" status.
      Clinical science articles published in high-impact specialized journals are most
      likely to be cited in the field of implant dentistry.

PMID- 28494040
TI  - Micro- to Macroroughness of Additively Manufactured Titanium Implants in Terms of
      Coagulation and Contact Activation.
AB  - PURPOSE: This study aimed to evaluate how as-built electron beam melting (EBM)
      surface properties affect the onset of blood coagulation. The properties of EBM
      manufactured implant surfaces for placement have, until now, remained largely
      unexplored in literature. Implants with conventional designs and custom-made
      implants have been manufactured using EBM technology and later placed into the
      human body. Many of the conventional implants used today, such as dental
      implants, display modified surfaces to optimize bone ingrowth, whereas custom
      made implants, by and large, have machined surfaces. However, titanium in itself
      demonstrates good material properties for the purpose of bone ingrowth. MATERIALS
      AND METHODS: Specimens manufactured using EBM were selected according to their
      surface roughness and process parameters. EBM-produced specimens, conventional
      machined titanium surfaces, as well as PVC surfaces for control were evaluated
      using the slide chamber model. RESULTS: A significant increase in activation was
      found, in all factors evaluated, between the machined samples and EBM
      manufactured samples. The results show that EBM-manufactured implants with as
      built surfaces augment the thrombogenic properties. CONCLUSION: EBM that uses
      Ti6Al4V powder appears to be a good manufacturing solution for load-bearing
      implants with bone anchorage. The as-built surfaces can be used "as is" for
      direct bone contact, although any surface treatment available for conventional
      implants can be performed on EBM-manufactured implants with a conventional
      design.

PMID- 28494041
TI  - Innovative Single-Tooth Replacement with an Individual Root-Analog Hybrid Implant
      in the Esthetic Zone: Case Report.
AB  - The goal of this study was to explore an innovative approach to single-tooth
      replacement using an individually custom-fabricated, root-analog, hybrid dental
      implant, in the esthetic zone, to avoid the microgap and micromovements between
      the implant and abutment. Moreover, the use of burs to prepare the implant
      recipient site is not necessary in this technique, reducing the bone removal,
      heating, and trauma. The process requires capturing accurate root geometry
      through combined computer-aided design/computer-assisted manufacturing (CAD/CAM)
      and a three-dimensional (3D) visualization (digital volume tomography [DVT]) of
      the tooth in situ, which might result in reduced remodeling after insertion. A
      good esthetic and functional outcome was obtained. The use of a root-shaped tooth
      analog implant might be in selected cases a viable alternative to current
      threaded cylindrical and cone-shaped implants. The new concept avoids the
      microgap between the implant and the abutment and reduces the trauma to the
      tissue and bone.

PMID- 28494042
TI  - Three-Dimensional Implant Positioning with a Piezosurgery Implant Site
      Preparation Technique and an Intraoral Surgical Navigation System: Case Report.
AB  - This case report describes new implant site preparation techniques joining the
      benefits of using an intraoral navigation system to optimize three-dimensional
      implant site positioning in combination with an ultrasonic osteotomy. A report of
      five patients is presented, and the implant positions as planned in the
      navigation software with the postoperative scan image were compared. The
      preliminary results are useful, although further clinical studies with larger
      populations are needed to confirm these findings.

PMID- 28494043
TI  - Maxillary Sinus Floor Augmentation Using Xenograft: Gene Expression and
      Histologic Analysis.
AB  - PURPOSE: Many histologic and histomorphometric studies as well as systematic
      reviews have shown the clinical success of the use of anorganic bovine bone (ABB,
      Bio-Oss) in maxillary sinus floor augmentation (MSFA). The molecular processes
      involved in bone healing are, however, still unknown. The aims of this study were
      to explore gene expression associated with bone remodeling and inflammation in
      MSFA sites. MATERIALS AND METHODS: The mRNA expression levels of runt related
      transcription factor 2 (RUNX2), receptor activator of NF-kB ligand (RANKL),
      osteoprotegerin (OPG), matrix metallopeptidase 9 (MMP-9), tartrate-resistance
      acid phosphatase (TRAP), and interleukin-1beta (IL-1beta), as well as the ratio
      of RANKL/OPG were compared between alveolar bone of a group after MSFA with ABB
      and a maxillary posterior edentulous bone group. Twenty-one bone samples were
      collected at the time of implant placement after 6 months of MSFA or tooth
      extraction. Fourteen bone samples from the MSFA group and from the maxillary
      posterior edentulous bone without MSFA group were taken to analyze gene
      expression by real-time reverse transcription polymerase chain reaction (RT-PCR).
      Seven bone samples from the MSFA group were used for histologic analysis.
      RESULTS: Real time RT-PCR revealed no statistically significant difference in
      gene expression level of RUNX2, RANKL, OPG, MMP-9, TRAP, and IL-1beta, or in the
      ratio of RANKL/OPG. Histology showed bone-lining cells at the edge and osteocyte
      inside newly formed bone. Residual grafted particles were in close contact with
      new bone. CONCLUSION: After a healing period of 6 months, ABB particles did not
      have an effect on the expression of genes associated with bone remodeling and
      inflammation. In addition, histologic evidence supports that ABB particles are
      replaced by new bone formation and do not affect bone healing.

PMID- 28494044
TI  - Placement of Zygomatic Implants into the Malar Prominence of the Maxillary Bone
      for Apical Fixation: A Clinical Report of 5 to 13 Years.
AB  - PURPOSE: This study was designed to evaluate long-term performance of zygomatic
      implants using an alternative apical fixation point to establish the posterior
      restorative foundation for fixed full-arch restoration. MATERIALS AND METHODS: A
      retrospective study of all consecutively treated patients with advanced maxillary
      resorption who were treated with zygomatic implants to support fixed prostheses
      from August 14, 2001 through November 24, 2009 was conducted; the final follow-up
      was August 31, 2015. All zygomatic implants were placed using the malar
      prominence of the maxillary bone for apical fixation. Initial study casts were
      analyzed to compute the anterior/posterior implant distribution, distance between
      bilateral zygomatic implants, and variation from ideal zygomatic implant
      positioning relative to the soft tissue crest. Soft tissue, implant, and
      restorative complications also were recorded. RESULTS: Fifty-eight consecutively
      treated patients with advanced maxillary resorption were included in the study-
      18 men and 40 women, with a mean +/- SD age of 65.3 +/- 8.0 years and range of 49
      to 85 years. Forty-nine patients received bilateral zygomatic implants placed
      apically into the malar process of the maxillary bone, and nine patients received
      similarly placed unilateral zygomatic implants with 107 zygomatic implants
      reported. All patients had supplemental anterior implants and were restored with
      a one-piece splint framework and fully implant-supported restoration. Follow-up
      of 5 to 13 years was conducted, with a mean follow-up time of 8.4 years per
      zygomatic implant. No losses of zygomatic implants occurred. No major surgical or
      restorative complications were observed. CONCLUSION: Utilizing the malar
      prominence of the maxilla for apical fixation of zygomatic implants predictably
      allows prosthetic placement of the implant platform in a favorable first molar
      position, eliminating prosthetic compromise.

PMID- 28494045
TI  - Survival Analysis of Orbital Implants and Potential Influencing Factors: A
      Retrospective Long-Term Study.
AB  - PURPOSE: Application of endosseous implants in prosthetic orbital reconstruction
      seems to be very successful, but few reports have evaluated cumulative survival
      rates of orbital implants over a long period. The aim of this study was to
      analyze long-term survival rates and potential influencing factors of orbital
      implants. MATERIALS AND METHODS: A retrospective evaluation of patients treated
      with extraoral screw implants for retaining orbital prostheses from 1991 to 2014
      was performed. Patient records were assessed for implant survival, demographic
      data, defect etiology, irradiation status, location of implant placement, implant
      systems, length, and retention type. Data were analyzed using the Kaplan-Meier
      method and log-rank test to compare survival curves. RESULTS: A total of 282
      orbital implants placed in 78 patients were evaluated during an observation
      period ranging from 2 to 268 months (mean: 94.97 months). The cumulative implant
      survival rate was 91.3% at 2 years, 80.5% at 5 years, 68.7% at 10 years, and
      62.2% after 15 years. The survival rate was significantly higher in females
      (75.3%) vs males (47.3%), in supraorbital vs infraorbital implants (67.4% vs
      51.5%), and in Branemark implants (70.2%) vs Straumann implants (54.5%).
      CONCLUSION: The presented data suggest that the long-term predictability of
      orbital implants revealed good to acceptable results. Factors such as female
      gender, localization in the supraorbital rim, a machined surface of the implant
      system, length, and magnetic retention seem to affect the implant survival rate
      positively, whereas irradiation status does not show any influence. These factors
      should be considered in planning future patient rehabilitation.

PMID- 28494047
TI  - Comparison of Marginal Bone Level Changes of Immediately Loaded Implants, Delayed
      Loaded Nonsubmerged Implants, and Delayed Loaded Submerged Implants: A Randomized
      Clinical Trial.
AB  - PURPOSE: The aim of this randomized clinical trial was to radiographically
      compare peri-implant marginal bone level changes between immediately loaded
      implants without the removal of an abutment placed at the time of surgery (IL),
      delayed loaded nonsubmerged implants (NS), and delayed loaded submerged implants
      (SI). MATERIALS AND METHODS: Patients' edentulous sites were randomly allocated
      to the three groups of implants so that each patient received one implant of each
      group. Digital periapical radiographs were obtained at baseline as well as three
      (T1), six (T2), and nine (T3) months after implant insertion. The mesial and
      distal bone crest levels adjacent to each implant were measured, and the mean
      values were calculated for each implant at each period. The data were
      statistically analyzed by repeated measures analysis of variance (ANOVA) and the
      Tukey test (P < .05). RESULTS: The patient sample comprised 15 subjects (13 women
      and 2 men; mean age: 47.7 years) with partially edentulous sites in the
      mandibular posterior area. Forty-five implants were inserted (15 IL implants, 15
      NS implants, and 15 SI implants). There was no statistically significant
      difference between the three groups with regard to changes in the marginal bone
      level during the follow-up period. The study achieved a 93.3% cumulative survival
      rate for both delayed loaded groups (NS and IS) and a 100% survival rate for the
      IL group. CONCLUSION: In the 9-month period following the implants, no
      statistically significant differences were found between immediately and delayed
      loaded implants or between submerged and nonsubmerged implants in bone level
      changes in patients with partial posterior mandibular edentulism.

PMID- 28494046
TI  - Traditional Postextractive Implant Site Preparation Compared with Pre-extractive
      Interradicular Implant Bed Preparation in the Mandibular Molar Region, Using an
      Ultrasonic Device: A Randomized Pilot Study.
AB  - PURPOSE: The immediate placement of single postextractive implants is increasing
      in the everyday clinical practice. Due to insufficient bone tissue volume, proper
      primary stability, essential for subsequent osseointegration, is sometimes not
      reached. The aim of this work was to compare two different approaches: implant
      bed preparation before and after root extraction. MATERIALS AND METHODS: Twenty
      two patients of both sexes were selected who needed an implant-prosthetic
      rehabilitation of the fractured first mandibular molar or presented an
      untreatable endodontic pathology. The sites were randomly assigned to the test
      group (treated with implant bed preparation before molar extractions) or control
      group (treated with implant bed preparation after molar extractions) by a
      computer-generated table. All implants were placed by the same operator, who was
      experienced in both traditional and ultrasonic techniques. The implant stability
      quotient (ISQ) and the position of the implant were evaluated. Statistical
      analysis was carried out. RESULTS: In the control group, three implants were
      placed in the central portion of the bone septum, while eight implants were
      placed with a tilted axis in relation to the septum; in the test group, all
      implants were placed in ideal positions within the root extraction sockets. The
      different position of the implants between the two procedures was statistically
      significant. CONCLUSION: This work presented an innovative approach for implant
      placement at the time of mandibular molar extraction. Preparing the implant bed
      with an ultrasonic device before root extraction is a simple technique and also
      allows greater stability to be reached in a selective case.

PMID- 28494048
TI  - Satisfaction and Patient-Related Outcomes in 128 Patients with Single Implant
      Crowns In Situ for up to 14 Years.
AB  - PURPOSE: To assess patient satisfaction and patient-related outcomes across the
      domains of appearance, cleansibility, and costs; the perceived value and worth
      when single implant crowns (SICs) had been in situ up to 14 years; whether
      satisfaction differed between patients; and whether certain characteristics might
      affect the questionnaire response rate. MATERIALS AND METHODS: Patients treated
      at a private prosthodontic practice between 2001 and 2014 (n = 207) who received
      a SIC (n = 256) were prospectively included. A previously validated patient
      satisfaction questionnaire (PSQ) exploring patient-centered outcomes was mailed
      to participants. Demographic (sex, age) and treatment data (number of SICs, time
      in situ, failure experience, complication experience) were collected. Visual
      analog scale (VAS) responses were converted to percentages. Differences between
      respondents and nonrespondents, differences in satisfaction between prosthesis
      placement and survey date, and differences with respect to demographic and
      treatment data were assessed. Averages were medians bounded by interquartile
      ranges. Statistical significance was set at P = .05. RESULTS: Respondents (n =
      128, 61.8%) and nonrespondents (n = 79, 38.2%) had similar demographic and
      treatment characteristics. Prostheses had been in situ for up to 14 years
      (median, 5 years; interquartile range [IQR], 24 to 96 months). Participants
      reported that treatment met their expectations (median, 93%; IQR, 85% to 100%);
      they reported high satisfaction with tooth color, tooth contour, peri-implant
      mucosa, appearance overall, and ease of cleaning (medians ranging from 90.5% to
      95%, IQR ranging from 80% to 100%) and medium satisfaction with costs when
      prostheses were placed (median, 50%; IQR, 29% to 80%). Satisfaction with tooth
      contour, peri-implant tissues, overall appearance, and costs significantly
      improved over time (96%, 92.5%, 91.7%, and 75%, respectively; P < .001 to P =
      .049). Levels of satisfaction did not differ by sex, number of implants,
      survival, complications, number of complications, and time in situ. Younger
      patients were less satisfied with the overall appearance and costs than older
      patients (P = .004, P = .007, respectively). All patients would choose to undergo
      treatment again and would recommend it to a friend. CONCLUSION: Patients with
      SICs that were in situ up to 14 years who responded to the validated PSQ were
      highly satisfied with the appearance and cleansibility, noted improvements in
      peri-implant tissue contours, and found the treatment to be valuable and
      worthwhile. They reported that upfront costs were high, but this concern
      decreased when the SICs had been in the mouth for a period of time.

PMID- 28494049
TI  - Assessment of Adhesion and Proliferation of Bone Marrow Mesenchymal Stem Cells in
      Polymer Matrices with rhGH.
AB  - PURPOSE: Biomaterials, as an alternative to autogenous bone and other biologic
      tissues, have been widely used in oral and maxillofacial surgery. In this
      context, a biomaterial that functions as a scaffold (osteoconductor), combined
      with a growth factor (osteoinductor), would be of great interest for clinical
      application. Biodegradable polymers used for slow drug release have been
      investigated, demonstrating good results and interesting potential. Growth
      hormone (GH) may be released by incorporating it into these polymers. This study
      aimed to evaluate cell adhesion and proliferation of a polymeric biomaterial for
      slow release of recombinant human GH (rhGH). MATERIALS AND METHODS: Poly(lactic
      co-glycolic acid) (PLGA) and PLGA/polycaprolactone (PCL) (at a 70/30 ratio of
      PLGA to PCL) matrices were prepared by the solvent evaporation method, combined
      or not with GH. Biomaterials were tested for cell adhesion and proliferation by
      culture in mesenchymal stem cells derived from Wistar rat bone marrow, 4',6
      diamidino-2-phenylindole (DAPI) staining, and subsequent cell counting, in
      addition to scanning electron microscopy. Cell adhesion and proliferation was
      assessed at 24 and 72 hours of biomaterial exposure to culture medium. RESULTS:
      All tested polymers exhibited cell adhesion and proliferation. However, PLGA
      based biomaterials, especially when combined with GH, showed greater cell
      proliferation when the difference in growth from 24 to 72 hours was evaluated. GH
      appeared to modify the polymer surface, with increased roughness and
      microporosity. This feature was more evident in the PLGA + GH combination.
      CONCLUSION: The biomaterials tested showed pronounced cell adhesion in all test
      groups, and GH appeared to contribute to the increase in cell proliferation,
      especially when combined with PLGA as compared with pure PLGA. Further studies
      are required to clarify this potential for development of new biomaterials.

PMID- 28494050
TI  - Determinants, Associations, Consequences, and Prevention of Readmissions After
      Transcatheter Aortic Valve Replacement.

PMID- 28494051
TI  - Declining Incidence Rates of Prostate Cancer in the United States: Is This Good
      News or Not?

PMID- 28494053
TI  - Myeloma Minimal Residual Disease and Surrogacy-Reply.

PMID- 28494054
TI  - Conservative Treatment of Isolated Cricoid Cartilage Fractures From Blunt Trauma.

PMID- 28494052
TI  - Association of Minimal Residual Disease With Clinical Outcome in Pediatric and
      Adult Acute Lymphoblastic Leukemia: A Meta-analysis.
AB  - Importance: Minimal residual disease (MRD) refers to the presence of disease in
      cases deemed to be in complete remission by conventional pathologic analysis.
      Assessing the association of MRD status following induction therapy in patients
      with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve
      the efficiency of clinical trials and accelerate drug development. Objective: To
      quantify the relationships between event-free survival (EFS) and overall survival
      (OS) with MRD status in pediatric and adult ALL using publications of clinical
      trials and other databases. Data Sources: Clinical studies in ALL identified via
      searches of PubMed, MEDLINE, and clinicaltrials.gov. Study Selection: Our search
      and study screening process adhered to the PRISMA Guidelines. Studies that
      addressed EFS or OS by MRD status in patients with ALL were included; reviews,
      abstracts, and studies with fewer than 30 patients or insufficient MRD
      description were excluded. Data Extraction and Synthesis: Study sample size,
      patient age, follow-up time, timing of MRD assessment (postinduction or
      consolidation), MRD detection method, phenotype/genotype (B cell, T cell,
      Philadelphia chromosome), and EFS and OS. Searches of PubMed and MEDLINE
      identified 566 articles. A parallel search on clinicaltrials.gov found 67 closed
      trials and 62 open trials as of 2014. Merging results of 2 independent searches
      and applying exclusions gave 39 publications in 3 arms of patient populations
      (adult, pediatric, and mixed). We performed separate meta-analyses for each of
      these 3 subpopulations. Results: The 39 publications comprised 13 637 patients:
      16 adult studies (2076 patients), 20 pediatric (11 249 patients), and 3 mixed
      (312 patients). The EFS hazard ratio (HR) for achieving MRD negativity is 0.23
      (95% Bayesian credible interval [BCI] 0.18-0.28) for pediatric patients and 0.28
      (95% BCI, 0.24-0.33) for adults. The respective HRs in OS are 0.28 (95% BCI, 0.19
      0.41) and 0.28 (95% BCI, 0.20-0.39). The effect was similar across all subgroups
      and covariates. Conclusions and Relevance: The value of having achieved MRD
      negativity is substantial in both pediatric and adult patients with ALL. These
      results are consistent across therapies, methods of and times of MRD assessment,
      cutoff levels, and disease subtypes. Minimal residual disease status warrants
      consideration as an early measure of disease response for evaluating new
      therapies, improving the efficiency of clinical trials, accelerating drug
      development, and for regulatory approval. A caveat is that an accelerated
      approval of a particular new drug using an intermediate end point, such as MRD,
      would require confirmation using traditional efficacy end points.

PMID- 28494055
TI  - Modern Management of Nasal Hemangiomas.
AB  - Importance: Current treatment approaches for infantile hemangiomas of the nose
      include observation, pharmacologic agents, surgery, and/or laser therapy. Because
      of the known functional, social, and cosmetic effect of nasal deformities,
      obtaining the best possible result is critical. Optimal timing, type, duration,
      and extent of therapy remain unclear. Observations: Results of a review of 86
      patients (64 females and 22 males; mean age, 4.8 months [range, 2 days-23 years])
      with infantile hemangiomas of the nose treated from January 1, 1999, to December
      31, 2015, and a review of the literature are presented to gain insight into the
      preferred approach to the treatment of these lesions. Patients underwent single
      modality and multimodality treatment with pulsed-dye laser (n = 73), oral
      corticosteroids (n = 11), intralesional corticosteroids (n = 2), propranolol
      hydrochloride (n = 30), and surgery (n = 50). The treatment decision algorithms
      and outcomes based on tumor phase and infantile hemangioma subtype are reviewed
      in detail. Nine articles met the criteria to be included in the literature
      review. Literature from the era before the approval of propranolol advocates for
      early use of oral or intralesional corticosteroids followed by surgery or pulsed
      dye laser in cases of unacceptable outcomes. Literature from the era after the
      approval of propranolol supports early initiation of oral beta-blockers until
      proliferation ceases or until additional intervention is necessary. Conclusions
      and Relevance: Despite a lack of higher levels of evidence, there exists a
      general consensus between the literature and clinical experience advocating for
      early multimodality treatment to achieve the best result possible by the time the
      children reach certain sociodevelopmental milestones.

PMID- 28494057
TI  - Biomechanics Education Redux.

PMID- 28494056
TI  - Comparison of Automated Posttonsillectomy Bleed Capture With Self-report.
AB  - Importance: Tonsillectomy is one of the most common procedures performed by
      otolaryngologists and is associated with postoperative bleeding. Bleed rates are
      usually monitored by self-report. Objective: To evaluate whether using automated
      capture and reporting of pediatric posttonsillectomy bleeding is feasible and
      accurate compared with traditional self-reporting by the surgical team. Design,
      Setting, and Participants: An automated complication-reporting algorithm was
      designed to query the local health information exchange and then tested against
      self-reported tonsillectomy complication data collected from January 1, 2014,
      through December 31, 2015, at a tertiary pediatric hospital. The algorithm
      identified patients undergoing tonsillectomy and searched their postoperative
      encounters for a hand-selected set of diagnosis codes from the International
      Classification of Diseases, Ninth Revision and International Statistical
      Classification of Diseases and Related Health Problems, Tenth Revision and free
      text words to identify complication events. Five months of the 2014-2015 data set
      were used to help design the algorithm. Data from the remaining 19 months were
      compared with self-reported complications. Main Outcomes and Measures: Automated
      system findings compared with self-reported bleeding events. Results: During the
      19-month period, 1017 tonsillectomies were performed. We compared the algorithm's
      effectiveness in finding tonsillectomy and adenotonsillectomy procedures for the
      evaluated surgeons with the hand-reviewed master tonsillectomy list. The
      algorithm reported 51 false-positive (5.01% missed) and 74 false-negative (7.28%
      misidentified) procedures. The algorithm agreed with self-report for 986
      tonsillectomies and disagreed on 31 cases (3.05%) (kappa = 0.69; 95% CI, 0.66
      0.73). The algorithm was found to be sensitive to correctly identifying 60.53%
      (95% CI, 48.63%-71.34%) of tonsillectomies as having bleeding complications, with
      a specificity of 98.30% (95% CI, 97.19%-98.99%). Conclusions and Relevance:
      Capture of posttonsillectomy bleeding is possible through an automatic search of
      the medical record, although the algorithm will require continued refinement.
      Leveraging health information exchange data increases the possibilities of
      capturing complications at hospitals outside the local health system. Use of
      these algorithms will allow repeatable automated feedback to be provided to
      surgeons on a cyclical basis.

PMID- 28494058
TI  - Management of Chronic Pain in the Aftermath of the Opioid Backlash.

PMID- 28494059
TI  - Health Literacy in Patients With Head and Neck Cancer: An Understudied Issue.

PMID- 28494060
TI  - beta-Zone Parapapillary Atrophy and Rates of Glaucomatous Visual Field
      Progression: African Descent and Glaucoma Evaluation Study.
AB  - Importance: beta-zone parapapillary atrophy (betaPPA) has been reported as a risk
      factor for glaucoma onset and progression. Previous studies have shown that the
      prevalence of betaPPA differs between individuals of African descent (AD) and
      European descent (ED). Objective: To test whether the association between the
      presence and progression of betaPPA vs visual field progression of glaucoma
      differs between these 2 ancestry groups. Design, Setting, and Participants: In a
      prospective, multicenter, longitudinal cohort study, 634 individuals (1090 eyes)
      enrolled in the African Descent and Evaluation Study (ADAGES) with a diagnosis of
      glaucomatous optic neuropathy (GON) or ocular hypertension (OHT) and at least 2
      disc stereophotographs were included. Two graders masked to clinical and ancestry
      data reviewed and graded the baseline and last disc stereophotographs for the
      presence of betaPPA at baseline and betaPPA progression (development or
      enlargement). Mixed-effects linear models were tested with visual field mean
      deviation as a dependent variable and time (alone and with interaction terms) as
      independent variables. ADAGES enrollment began in January 2003 and ended in July
      2006; follow-up ended in 2016. Exposures: Disc stereophotographs. Main Outcomes
      and Measures: Progression of betaPPA in AD and ED individuals. Results: In 634
      patients, a total of 814 eyes of AD (395 eyes) and ED (419) patients with GON and
      276 eyes of AD (106) and ED (170) patients with OHT who were enrolled in ADAGES
      were analyzed. There were 336 (53.0%) women in the study; mean (SD) age was 61.9
      (12.7) years. In the OHT group, the association between betaPPA at baseline and
      visual field progression was not significantly different between AD and ED eyes
      (beta = 0.071; 95% CI, -0.016 to 0.158; P = .11), nor was the association between
      betaPPA progression and visual field progression (beta = 0.020; 95% CI, -0.465 to
      0.506; P = .93). In the GON group, ED eyes with baseline betaPPA progressed
      faster than did AD eyes with baseline betaPPA (beta = -0.124; 95% CI, -0.241 to 
      0.007; P = .04), although the association between betaPPA progression and visual
      field progression did not differ significantly between race groups (beta = 
      0.101; 95% CI, -0.323 to 0.119; P = .37). Conclusions and Relevance: Race had a
      significant effect on the association between baseline betaPPA and rates of
      visual field progression in eyes with GON. Progression of betaPPA was not
      associated with faster visual field progression in either racial group.

PMID- 28494062
TI  - Conjunctival Lesion in a Patient With Ocular Graft-vs-Host Disease.

PMID- 28494061
TI  - Association Between Hospital Volume and 30-Day Readmissions Following
      Transcatheter Aortic Valve Replacement.
AB  - Importance: With the approval of transcatheter aortic valve replacement (TAVR)
      for patients with severe symptomatic aortic stenosis at intermediate surgical
      risk, TAVR volume is projected to increase exponentially in the United States.
      The 30-day readmission rate for TAVR was recently reported at 17.9%. The
      association between institutional TAVR volume and the 30-day readmission metric
      has not been examined. Objective: To assess the association between hospital TAVR
      volume and 30-day readmission. Design, Setting, and Participants: In this
      observational study, we used the 2014 Nationwide Readmissions Database to
      identify hospitals with established TAVR programs (performing at least 5 TAVRs in
      the first quarter of 2014). Based on annual TAVR volume, hospitals were
      classified as low (<50), medium (>=50 to <100), and high (>=100) volume. Rates,
      causes, and costs of 30-day readmissions were compared between low-, medium-, and
      high-volume hospitals. Data were analyzed from November to December 2016.
      Exposure: Transcatheter aortic valve replacement. Main Outcomes and Measures:
      Thirty-day readmissions. Results: Of 129 hospitals included in this study, 20
      (15.5%) were categorized as low volume, 47 (36.4%) as medium volume, and 62
      (48.1%) as high volume. Of 16 252 index TAVR procedures, 663 (4.1%), 3067
      (18.9%), and 12 522 (77.0%) were performed at low-, medium-, and high-volume
      hospitals, respectively. Thirty-day readmission rates were significantly lower in
      high-volume compared with medium-volume (adjusted odds ratio, 0.76; 95% CI, 0.68
      0.85; P < .001) and low-volume (adjusted odds ratio, 0.75; 95% CI, 0.60-0.92; P =
      .007) hospitals. Noncardiac readmissions were more common in low-volume hospitals
      (65.6% vs 60.6% in high-volume hospitals), whereas cardiac readmissions were more
      common in high-volume hospitals (39.4% vs 34.4% in low-volume hospitals). There
      were no significant differences in length of stay and costs per readmission among
      the 3 groups (mean [SD], 5.5 [5.0] days vs 5.9 [7.5] days vs 6.0 [5.8] days; P =
      .74, and $13 886 [18 333] vs $14 135 [17 939] vs $13 432 [15 725]; P = .63,
      respectively). Conclusions and Relevance: We report for the first time, to our
      knowledge, an inverse association between hospital TAVR volume and 30-day
      readmissions. Lower readmission at higher-volume hospitals was associated with
      significantly lower cost to the health care system.

PMID- 28494064
TI  - Myeloma Minimal Residual Disease and Surrogacy.

PMID- 28494065
TI  - Alternative Pathways to Board Recertification: To What End?

PMID- 28494063
TI  - Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis.
AB  - Importance: Some uncertainty about the clinical value and dosing of atropine for
      the treatment of myopia in children remains. Objective: To evaluate the efficacy
      vs the adverse effects of various doses of atropine in the therapy for myopia in
      children. Data Sources: Data were obtained from PubMed, EMBASE, and the Cochrane
      Central Register of Controlled Trials, from inception to April 30, 2016. The
      reference lists of published reviews and clinicaltrials.gov were searched for
      additional relevant studies. Key search terms included myopia, refractive errors,
      and atropine. Only studies published in English were included. Study Selection:
      Randomized clinical trials and cohort studies that enrolled patients younger than
      18 years with myopia who received atropine in at least 1 treatment arm and that
      reported the annual rate of myopia progression and/or any adverse effects of
      atropine therapy were included in the analysis. Data Extraction and Synthesis:
      Two reviewers independently abstracted the data. Heterogeneity was statistically
      quantified by Q, H, and I2 statistics, and a meta-analysis was performed using
      the random-effects model. The Cochrane Collaboration 6 aspects of bias and the
      Newcastle-Ottawa Scale were used to assess the risk for bias. Main Outcomes and
      Measures: The primary outcome was a difference in efficacy and the presence of
      adverse effects at different doses of atropine vs control conditions. The
      secondary outcomes included the differences in adverse effects between Asian and
      white patients. Results: Nineteen unique studies involving 3137 unique children
      were included in the analysis. The weighted mean differences between the atropine
      and control groups in myopia progression were 0.50 diopters (D) per year (95% CI,
      0.24-0.76 D per year) for low-dose atropine, 0.57 D per year (95% CI, 0.43-0.71 D
      per year) for moderate-dose atropine, and 0.62 D per year (95% CI, 0.45-0.79 D
      per year) for high-dose atropine (P < .001), which translated to a high effect
      size (Cohen d, 0.97, 1.76, and 1.94, respectively). All doses of atropine,
      therefore, were equally beneficial with respect to myopia progression (P = .15).
      High-dose atropine were associated with more adverse effects, such as the 43.1%
      incidence of photophobia compared with 6.3% for low-dose atropine and 17.8% for
      moderate-dose atropine (chi22 = 7.05; P = .03). In addition, differences in the
      incidence of adverse effects between Asian and white patients were not identified
      (chi21 = 0.81; P = .37 for photophobia). Conclusions and Relevance: This meta
      analysis suggests that the efficacy of atropine is dose independent within this
      range, whereas the adverse effects are dose dependent.

PMID- 28494066
TI  - Association Between Middle Ear Cholesteatoma and Chronic Rhinosinusitis.
AB  - Importance: Chronic rhinosinusitis (CRS) can cause an obstruction of the tubal
      orifice and thereby compromise ventilation of the middle ear. The resulting
      negative pressure in the middle ear may, in turn, lead to the formation of an
      eardrum retraction pocket and subsequent acquired cholesteatoma. This study
      hypothesizes that CRS may increase the risk of cholesteatoma. Objective: To
      evaluate the risk of cholesteatoma in patients with CRS. Design, Setting, and
      Participants: This study used a nationwide, population-based claims database to
      test the hypothesis that CRS may increase the risk of cholesteatoma. The
      Longitudinal Health Insurance Database of Taiwan was used to compile data from
      (1) 12 670 patients with newly diagnosed CRS between January 1, 1997, and
      December 31, 2002, and (2) a comparison cohort of 63 350 matched individuals
      without CRS, resulting in a CRS vs control ratio of 1:5. Data analysis was
      performed from June 1 to October 27, 2015. Each patient was followed up for 8
      years to identify those in whom cholesteatoma subsequently developed. The Kaplan
      Meier method was used to determine the cholesteatoma-free survival rate, and the
      log-rank test was used to compare survival curves. Cox proportional hazards
      regression models were used to compute the 8-year hazard ratios (HRs). Main
      Outcomes and Measures: Diagnosis of cholesteatoma. Results: Among the 76 020
      patients enrolled in this study, 35 220 (46.3%) were female; mean (SD) age was
      27.57 (22.03) years. A total of 209 patients developed cholesteatoma, 66 (101 084
      person-years) individuals from the CRS cohort and 143 (506 540 person-years) from
      the comparison cohort were diagnosed with cholesteatoma during the 8-year follow
      up period. The incidence of cholesteatoma per 1000 person-years was more than
      twice as high among patients with CRS (0.65; 95% CI, 0.50-0.81 person-years) than
      among those without CRS (0.28; 95% CI, 0.24-0.33). The absolute difference in the
      incidence density between CRS and non-CRS group was 0.37 (95% CI, 0.21-0.53) per
      1000 patient-years. After adjusting for potential confounders, patients with CRS
      had a 69% increased risk of cholesteatoma within 8 years, compared with those
      without CRS (HR, 1.69; 95% CI, 1.23-2.32). Patients with CRS presented a
      significantly lower 8-year cholesteatoma-free survival rate than did those in the
      comparison group. The absolute difference in the 8-year cholesteatoma-free
      survival rate between the CRS and non-CRS groups was 0.0029 (95% CI, 0.0016
      0.0043). Conclusions and Relevance: This is the first large-scale study, to date,
      to demonstrate a prospective link between CRS and the subsequent development of
      cholesteatoma within a follow-up period of 8 years. The purpose of the study was
      to draw attention to the possibility of development of cholesteatoma among
      patients with CRS. Because that possibility exists, clinicians should keep this
      association in mind as well as the importance of a thorough head and neck
      examination.

PMID- 28494067
TI  - Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery
      in an Adult Mediterranean Population: A Secondary Analysis of a Randomized
      Clinical Trial.
AB  - Importance: Cataract, one of the most frequent causes of blindness in developed
      countries, is strongly associated with aging. The exact mechanisms underlying
      cataract formation are still unclear, but growing evidence suggests a potential
      role of inflammatory and oxidative processes. Therefore, antioxidant and anti
      inflammatory factors of the diet, such as vitamin K1, could play a protective
      role. Objective: To examine the association between dietary vitamin K1 intake and
      the risk of incident cataracts in an elderly Mediterranean population. Design,
      Setting, and Participants: A prospective analysis was conducted in 5860
      participants from the Prevencion con Dieta Mediterranea Study, a randomized
      clinical trial executed between 2003 and 2011. Participants were community
      dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1)
      years. Main Outcomes and Measures: Dietary vitamin K1 intake was evaluated using
      a validated food frequency questionnaire. The time to the cataract event was
      calculated as the time between recruitment and the date of the occurrence to
      cataract surgery, the time to the last visit of the follow-up, date of death, or
      the end of the study. Hazard ratios and 95% CIs for cataract incidence were
      estimated with a multivariable Cox proportional hazards model. Results:
      Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n =
      1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years
      follow-up, we documented a total of 768 new cataracts. Participants in the
      highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than
      those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P = .002),
      after adjusting for potential confounders. Conclusions and Relevance: High intake
      of dietary vitamin K1 was associated with a reduced risk of cataracts in an
      elderly Mediterranean population even after adjusting by other potential
      confounders. Trial Registration: isrctn.org: ISRCTN35739639.

PMID- 28494068
TI  - A Comparison of Costal Cartilage Warping Using Oblique Split vs Concentric
      Carving Methods.
AB  - Importance: Warping of costal cartilage is well described; however, its strength
      and abundance still make it a desirable graft material, especially in complex
      reconstructive rhinoplasty. Despite multiple methods of cartilage harvest,
      carving, and preimplantation treatment being developed over the years, warp
      remains a challenging clinical problem. Objective: To assess whether the 30
      degrees  oblique split method of preparing costal cartilage grafts produces less
      warping of the graft than the current standard of harvesting the central segment
      of a rib using the concentric carving method. Design, Setting, and Participants:
      This in vitro cadaveric study evaluated the warping of costal cartilage grafts
      using the oblique split method with an angle of 30 degrees  or the concentric
      carving method during a 3-month period beginning in December 2014. Main Outcomes
      and Measures: Millimeters of warp from baseline (at 1 hour) and at 1, 2, and 3
      months, measured in the frontal and lateral planes. Results: Among 74 costal
      cartilage grafts (using the oblique split method with an angle of 30 degrees  in
      41 and the concentric carving method in 33), the mean amount of warp in the
      frontal plane was between 1.12 mm (95% CI, 0.96-1.28 mm) and 1.57 mm (95% CI,
      0.94-2.20 mm) for the oblique group and between 1.18 mm (95% CI, 0.98-1.38 mm)
      and 1.29 mm (95% CI, 0.86-1.72 mm) for the concentric group during the 3-month
      period. There was no statistically significant difference in the frontal plane
      between the 2 methods at 1 hour (P = .45; 0.10 mm, 95% CI, -0.38 to 0.17 mm), 1
      month (P = .32; 0.13 mm, 95% CI, -0.13 to 0.40 mm), 2 months (P = .50; 0.28 mm,
      95% CI, -0.55 to 1.11 mm), or 3 months (P = .15; 0.22 mm, 95% CI, -0.08 to 0.52
      mm) using the t test, regression analysis, or panel data analysis. Similarly, no
      significant difference was found in the lateral plane at 1 hour (P = .89; 0.04
      mm, 95% CI, -0.49 to 0.56 mm), 1 month (P = .82; 0.07 mm, 95% CI, -0.56 to 0.70
      mm), 2 months (P = .29; 0.40 mm, 95% CI, -0.36 to 1.17 mm), or 3 months (P = .63;
      0.22 mm, 95% CI, -0.70 to 1.13 mm) using the t test. Two grafts were excluded due
      to desiccation. Conclusions and Relevance: The 30 degrees  oblique split and
      concentric carving methods of costal cartilage graft carving are equivalent in
      terms of the amount of warp. The oblique split method may be superior because of
      easier carving and the increased volume of material. Level of Evidence: NA.

PMID- 28494072
TI  - Prognostic and Predictive Value of a Breast Cancer Expression Signature in
      Localized Prostate Cancer.

PMID- 28494071
TI  - Correlation Between Dynamic Contour Tonometry, Uncorrected and Corrected Goldmann
      Applanation Tonometry, and Stage of Glaucoma.
AB  - Importance: Accurate determination of intraocular pressure (IOP) is crucial for
      the diagnosis and management of glaucoma. Objective clinical evaluation of the
      correction equations for Goldmann applanation tonometry (GAT) is lacking.
      Objectives: To investigate the difference between corrected and conventional GAT
      and Pascal dynamic contour tonometry (DCT) measurements, as well as the
      correlation between discordant IOP values and stage of glaucoma. Design, Setting,
      and Participants: This prospective cross-sectional case series was conducted at
      the Department of Ophthalmology, University Hospital Zurich, and Talacker Eye
      Center between July 1, 2011, and May 31, 2016, among 112 white patients with
      glaucoma. Interventions: Intraocular pressure measurements were performed with
      GAT and DCT in a randomized order. Goldmann applanation tonometry measurements
      were modified with 5 correction equations. Main Outcomes and Measures: The
      primary end point was degree of concordance between corrected or uncorrected GAT
      and DCT measurements. The secondary end point was association between discordant
      IOP measurements and the stage of glaucoma, as assessed by the Glaucoma Severity
      Score. Results: Among the 112 patients (67 women and 45 men; mean [SD] age, 66.3
      [13.1] years), 63 of the eyes in the study (56.3%) were left eyes and 85 patients
      (75.9%) were taking ocular antihypertensive medications. Mean (SD) IOP was 20.3
      (4.5) mm Hg (95% CI, 19.4-21.1) as measured by DCT and 17.0 [4.1] mm Hg (95% CI,
      16.3-17.8) as measured by GAT. The mean (SD) discordance between DCT and GAT
      measurements was -3.3 (2.0) mm Hg (95% CI, 2.9-3.6). The 5 corrected GAT values
      ranged from -2.7 to -5.4 mm Hg compared with DCT. The mean (SD) result of the
      Dresdner correction formula (17.6 [4.1] mm Hg) was closer to the DCT measurement
      than the original GAT measurement. The mean (SD) Glaucoma Severity Score was 4.7
      (3.4) (95% CI, 4.1-5.4). The uncorrected discordance IOPDCT - IOPGAT showed a
      positive correlation with the Glaucoma Severity Score (rs = 0.33; P < .001) and a
      negative correlation with central corneal thickness (rs = -0.22; P = .02).
      Conclusions and Relevance: In comparison with DCT measurements, these data
      suggest that GAT values are significantly discordant in eyes with thin corneas
      and advanced glaucoma. Application of GAT-based correction formulas involves a
      possible risk of creating an even greater number of unpredictable measurement
      errors. Hence, we advise with caution, especially pertaining to eyes with thin
      corneas, to not place reliance on GAT readings, and abandon any correction
      formula. Trial Registration: clinicaltrials.gov Identifier: NCT01474070.

PMID- 28494074
TI  - Stop "Adjusting" Intraocular Pressure Measurements.

PMID- 28494073
TI  - Associations of Luminal and Basal Subtyping of Prostate Cancer With Prognosis and
      Response to Androgen Deprivation Therapy.
AB  - Importance: There is a clear need for a molecular subtyping approach in prostate
      cancer to identify clinically distinct subgroups that benefit from specific
      therapies. Objectives: To identify prostate cancer subtypes based on luminal and
      basal lineage and to determine associations with clinical outcomes and response
      to treatment. Design, Setting, and Participants: The PAM50 classifier was used to
      subtype 1567 retrospectively collected (median follow-up, 10 years) and 2215
      prospectively collected prostate cancer samples into luminal- and basal-like
      subtypes. Main Outcomes and Measures: Metastasis, biochemical recurrence, overall
      survival, prostate cancer-specific survival, associations with biological
      pathways, and clinicopathologic variables were the main outcomes. Results: Among
      the 3782 samples, the PAM50 classifier consistently segregated prostate cancer
      into 3 subtypes in both the retrospective and prospective cohorts: luminal A
      (retrospective, 538 [34.3%]; prospective, 737 [33.3%]), luminal B (retrospective,
      447 [28.5%]; prospective, 723 [32.6%]), and basal (retrospective, 582 [37.1%];
      prospective, 755 [34.1%]). Known luminal lineage markers, such as NKX3.1 and
      KRT18, were enriched in luminal-like cancers, and the basal lineage CD49f
      signature was enriched in basal-like cancers, demonstrating the connection
      between these subtypes and established prostate cancer biology. In the
      retrospective cohort, luminal B prostate cancers exhibited the poorest clinical
      prognoses on both univariable and multivariable analyses accounting for standard
      clinicopathologic prognostic factors (10-year biochemical recurrence-free
      survival [bRFS], 29%; distant metastasis-free survival [DMFS], 53%; prostate
      cancer-specific survival [PCSS], 78%; overall survival [OS], 69%), followed by
      basal prostate cancers (10-year bRFS, 39%; DMFS, 73%; PCSS, 86%; OS, 80%) and
      luminal A prostate cancers (10-year bRFS, 41%; DMFS, 73%; PCSS, 89%; OS, 82%).
      Although both luminal-like subtypes were associated with increased androgen
      receptor expression and signaling, only luminal B prostate cancers were
      significantly associated with postoperative response to androgen deprivation
      therapy (ADT) in a subset analysis in our retrospective cohorts (n = 315)
      matching patients based on clinicopathologic variables (luminal B 10-year
      metastasis: treated, 33% vs untreated, 55%; nonluminal B 10-year metastasis:
      treated, 37% vs untreated, 21%; P = .006 for interaction). Conclusions and
      Relevance: Luminal- and basal-like prostate cancers demonstrate divergent
      clinical behavior, and patients with luminal B tumors respond better to
      postoperative ADT than do patients with non-luminal B tumors. These findings
      contribute novel insight into prostate cancer biology, providing a potential
      clinical tool to personalize ADT treatment for prostate cancer by predicting
      which men may benefit from ADT after surgery.

PMID- 28494076
TI  - The Balance Between Access and Quality in Transcatheter Valve Therapies.

PMID- 28494077
TI  - Inadvertent Subconjunctival Injection of a Dexamethasone Implant.

PMID- 28494078
TI  - Exclusion of Traumatic Anterior Capsule Laceration Using Anterior Segment Optical
      Coherence Tomography.

PMID- 28494075
TI  - Six-Year Incidence and Progression of Age-Related Macular Degeneration in Kenya:
      Nakuru Eye Disease Cohort Study.
AB  - Importance: The incidence of age-related macular degeneration (AMD) is unknown in
      Africa. Objective: To estimate the 6-year cumulative incidence and progression of
      AMD in older adults (>=50 years old) in Nakuru, Kenya. Design, Setting, and
      Participants: This study assessed a population-based cohort with 6-year follow-up
      of 4414 participants who had a complete assessment. Random cluster sampling with
      probability proportionate to size procedures was used to select a representative,
      cross-sectional sample of adults 50 years and older from January 26, 2007,
      through November 11, 2008. A 6-year follow-up was undertaken from January 7,
      2013, through March 12, 2014. On both occasions, a comprehensive ophthalmic
      examination was performed that included logMAR visual acuity, digital retinal
      photography, and grading of images at Moorfields Eye Hospital Reading Centre.
      Data were collected on general health and risk factors. Main Outcomes and
      Measures: Incident AMD in participants with no AMD at baseline and progression
      from early to late AMD. Results: A total of 1453 of the 2900 individuals (50.1%)
      at risk for AMD were followed up after 6 years (mean [SD] age, 60.7 [8.2] years;
      635 female [49.5%]; 799 Kikuyu [62.3%], 324 Kalenjin [25.3%], and 159 other
      [12.4%]); 1282 had data on AMD status at follow-up. Of these, 202 developed early
      AMD, and no participants developed late AMD. The 6-year weighted (for loss to
      follow-up) cumulative incidence of early AMD was 164.2 per 1000 persons (95% CI,
      136.7-195.9 per 1000 persons). Two individuals with baseline early AMD from the
      142 at risk had developed late AMD at follow-up, with a 6-year cumulative
      incidence of progression from early to late AMD of 24.5 per 1000 persons (95% CI,
      5.0-111.7 per 1000 persons). Cumulative incidence of AMD increased with age (>=80
      years old vs 50-59 years old: 1.8; 95% CI, 0.9-3.5) and was higher in women
      (female vs male: 1.6; 95% CI, 1.2-2.1) and persons with diabetes (diabetes vs no
      diabetes: 1.7; 95% CI, 1.0-2.8). Conclusions and Relevance: In Kenya, more than
      100 000 estimated new cases of AMD, mainly early AMD, will develop every year in
      individuals 50 years or older, although a 50% loss to follow-up and wide CIs for
      progression to late AMD limit definitive conclusions from these findings.

PMID- 28494079
TI  - Numerous Smokestack and Inkblot Pattern Leaks in Central Serous
      Chorioretinopathy.

PMID- 28494080
TI  - Maxillary Sinus Wall Thickening in Silent Sinus Syndrome.

PMID- 28494084
TI  - The use of high throughput DNA sequence analysis to assess the endophytic
      microbiome of date palm roots grown under different levels of salt stress.
AB  - Date palms are able to grow under diverse abiotic stress conditions including in
      saline soils, where microbial communities may be help in the plant's salinity
      tolerance. These communities able to produce specific growth promoting substances
      can enhance date palm growth in a saline environment. However, these communities
      are poorly defined. In the work reported here, the date palm endophytic bacterial
      and fungal communities were identified using the pyrosequencing method, and the
      microbial differential abundance in the root upon exposure to salinity stress was
      estimated. Approximately 150,061 reads were produced from the analysis of six
      ribosomal DNA libraries, which were prepared from endophytic microorganisms
      colonizing date palm root tissues. DNA sequence analysis of these libraries
      predicted the presence of a variety of bacterial and fungal endophytic species,
      some known and others unknown. The microbial community compositions of 30% and 8%
      of the bacterial and fungal species, respectively, were significantly (p <= 0.05)
      altered in response to salinity stress. Differential enrichment analysis showed
      that microbe diversity indicated by the Chao, Shannon and Simpson indices were
      slightly reduced, however, the overall microbial community structures were not
      significantly affected as a consequence of salinity. This may reflect a buffering
      effect by the host plant on the internal environments that these communities are
      colonizing. Some of the endophytes identified in this study were strains that
      were previously isolated from saline and marine environments. This suggests
      possible interactions with the plant that are favorable to salinity tolerance in
      date palm. [Int Microbiol 19(3):143-155 (2016)].

PMID- 28494083
TI  - Phosphate: from stardust to eukaryotic cell cycle control.
AB  - Phosphorus is a pivotal element in all biochemical systems: it serves to store
      metabolic energy as ATP, it forms the backbone of genetic material such as RNA
      and DNA, and it separates cells from the environment as phospholipids. In
      addition to this "big hits", phosphorus has recently been shown to play an
      important role in other important processes such as cell cycle regulation. In the
      present review, we briefly summarize the biological processes in which phosphorus
      is involved in the yeast Saccharomyces cerevisiae before discussing our latest
      findings on the role of this element in the regulation of DNA replication in this
      eukaryotic model organism. We describe both the role of phosphorus in the
      regulation of G1 progression by means of the Cyclin Dependent Kinase (CDK) Pho85
      and the stabilization of the cyclin Cln3, as well as the role of other molecule
      composed of phosphorus-the polyphosphate-in cell cycle progression, dNTP
      synthesis, and genome stability. Given the eminent role played by phosphorus in
      life, we outline the future of phosphorus in the context of one of the main
      challenges in human health: cancer treatment. [Int Microbiol 19(3):133-141
      (2016)].

PMID- 28494085
TI  - Atypical enteropathogenic Escherichia coli (aEPEC) in children under five years
      old with diarrhea in Quito (Ecuador).
AB  - Enteropathogenic Escherichia coli (EPEC) remain one the most important pathogens
      infecting children and they are one of the main causes of persistent diarrhea
      worldwide. In this study, we have isolated EPEC from 94 stool samples of children
      under five years old with diarrheal illness in the area of Quito (Ecuador), and
      we have determined the occurrence of the two subtypes of EPEC, typical EPEC
      (tEPEC) and atypical (aEPEC), by PCR amplification of the genes eae (attaching
      and effacing) and bfp (bundle- forming pilus). Typical EPEC is positive for eae
      and bfp genes while aEPEC is positive only for eae. Our results suggest that
      aEPEC is the most prevalent subtype in Quito (89.36 %), while subtype tEPEC is
      less prevalent (10.64 %). [Int Microbiol 19(3):157-160 (2016)].

PMID- 28494086
TI  - Functional ecology of soil microbial communities along a glacier forefield in
      Tierra del Fuego (Chile).
AB  - A previously established chronosequence from Pia Glacier forefield in Tierra del
      Fuego (Chile) containing soils of different ages (from bare soils to forest ones)
      is analyzed. We used this chronosequence as framework to postulate that microbial
      successional development would be accompanied by changes in functionality. To
      test this, the GeoChip functional microarray was used to identify diversity of
      genes involved in microbial carbon and nitrogen metabolism, as well as other
      genes related to microbial stress response and biotic interactions. Changes in
      putative functionality generally reflected succession-related taxonomic
      composition of soil microbiota. Major shifts in carbon fixation and catabolism
      were observed, as well as major changes in nitrogen metabolism. At initial
      microbial dominated succession stages, microorganisms could be mainly involved in
      pathways that help to increase nutrient availability, while more complex
      microbial transformations such as denitrification and methanogenesis, and later
      degradation of complex organic substrates, could be more prevalent at vegetated
      successional states. Shifts in virus populations broadly reflected changes in
      microbial diversity. Conversely, stress response pathways appeared relatively
      well conserved for communities along the entire chronosequence. We conclude that
      nutrient utilization is likely the major driver of microbial succession in these
      soils. [Int Microbiol 19(3):161-173 (2016)].

PMID- 28494087
TI  - Investigation of twenty selected medicinal plants from Malaysia for anti
      Chikungunya virus activity.
AB  - Chikungunya virus is a reemerging arbovirus transmitted mainly by Aedes
      mosquitoes. As there are no specific treatments available, Chikungunya virus
      infection is a significant public health problem. This study investigated 120
      extracts from selected medicinal plants for anti-Chikungunya virus activity. The
      plant materials were subjected to sequential solvent extraction to obtain six
      different extracts for each plant. The cytotoxicity and antiviral activity of
      each extract were examined using African monkey kidney epithelial (Vero) cells.
      The ethanol, methanol and chloroform extracts of Tradescantia spathacea
      (Commelinaceae) leaves showed the strongest cytopathic effect inhibition on Vero
      cells, resulting in cell viabilities of 92.6% +/- 1.0% (512 MUg/ml), 91.5% +/-
      1.7% (512 MUg/ml) and 88.8% +/- 2.4% (80 MUg/ml) respectively. However,
      quantitative RT-PCR analysis revealed that the chloroform extract of Rhapis
      excelsa (Arecaceae) leaves resulted in the highest percentage of reduction of
      viral load (98.1%), followed by the ethyl acetate extract of Vernonia amygdalina
      (Compositae) leaves (95.5%). The corresponding 50% effective concentrations
      (EC50) and selectivity indices for these two extracts were 29.9 +/- 0.9 and 32.4
      +/- 1.3 MUg/ml, and 5.4 and 5.1 respectively. Rhapis excelsa and Vernonia
      amygdalina could be sources of anti-Chikungunya virus agents. [Int Microbiol
      19(3):175-182 (2016)].

PMID- 28494088
TI  - Peripheral nerve blocks for hip fractures.
AB  - BACKGROUND: Various nerve blocks with local anaesthetic agents have been used to
      reduce pain after hip fracture and subsequent surgery. This review was published
      originally in 1999 and was updated in 2001, 2002, 2009 and 2017. OBJECTIVES: This
      review focuses on the use of peripheral nerves blocks as preoperative analgesia,
      as postoperative analgesia or as a supplement to general anaesthesia for hip
      fracture surgery. We undertook the update to look for new studies and to update
      the methods to reflect Cochrane standards. SEARCH METHODS: For the updated
      review, we searched the following databases: the Cochrane Central Register of
      Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE (Ovid SP, 1966 to August week
      1 2016), Embase (Ovid SP, 1988 to 2016 August week 1) and the Cumulative Index to
      Nursing and Allied Health Literature (CINAHL) (EBSCO, 1982 to August week 1
      2016), as well as trial registers and reference lists of relevant articles.
      SELECTION CRITERIA: We included randomized controlled trials (RCTs) involving use
      of nerve blocks as part of the care provided for adults aged 16 years and older
      with hip fracture. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed new trials for inclusion, determined trial quality using the Cochrane
      tool and extracted data. When appropriate, we pooled results of outcome measures.
      We rated the quality of evidence according to the GRADE Working Group approach.
      MAIN RESULTS: We included 31 trials (1760 participants; 897 randomized to
      peripheral nerve blocks and 863 to no regional blockade). Results of eight trials
      with 373 participants show that peripheral nerve blocks reduced pain on movement
      within 30 minutes of block placement (standardized mean difference (SMD) -1.41,
      95% confidence interval (CI) -2.14 to -0.67; equivalent to -3.4 on a scale from 0
      to 10; I2 = 90%; high quality of evidence). Effect size was proportionate to the
      concentration of local anaesthetic used (P < 0.00001). Based on seven trials with
      676 participants, we did not find a difference in the risk of acute confusional
      state (risk ratio (RR) 0.69, 95% CI 0.38 to 1.27; I2 = 48%; very low quality of
      evidence). Three trials with 131 participants reported decreased risk for
      pneumonia (RR 0.41, 95% CI 0.19 to 0.89; I2 = 3%; number needed to treat for an
      additional beneficial outcome (NNTB) 7, 95% CI 5 to 72; moderate quality of
      evidence). We did not find a difference in risk of myocardial ischaemia or death
      within six months, but the number of participants included was well below the
      optimal information size for these two outcomes. Two trials with 155 participants
      reported that peripheral nerve blocks also reduced time to first mobilization
      after surgery (mean difference -11.25 hours, 95% CI -14.34 to -8.15 hours; I2 =
      52%; moderate quality of evidence). One trial with 75 participants indicated that
      the cost of analgesic drugs was lower when they were given as a single shot block
      (SMD -3.48, 95% CI -4.23 to -2.74; moderate quality of evidence). AUTHORS'
      CONCLUSIONS: High-quality evidence shows that regional blockade reduces pain on
      movement within 30 minutes after block placement. Moderate-quality evidence shows
      reduced risk for pneumonia, decreased time to first mobilization and cost
      reduction of the analgesic regimen (single shot blocks).

PMID- 28494089
TI  - Evaluation of the tumor registration error in biopsy procedures performed under
      real-time PET/CT guidance.
AB  - PURPOSE: The purpose of this study is to quantify tumor displacement during real
      time PET/CT guided biopsy and to investigate correlations between tumor
      displacement and false-negative results. METHODS: 19 patients who underwent real
      time 18 F-FDG PET-guided biopsy and were found positive for malignancy were
      included in this study under IRB approval. PET/CT images were acquired for all
      patients within minutes prior to biopsy to visualize the FDG-avid region and plan
      the needle insertion. The biopsy needle was inserted and a post-insertion CT scan
      was acquired. The two CT scans acquired before and after needle insertion were
      registered using a deformable image registration (DIR) algorithm. The DIR
      deformation vector field (DVF) was used to calculate the mean displacement
      between the pre-insertion and post-insertion CT scans for a region around the tip
      of the biopsy needle. For 12 patients one biopsy core from each was tracked
      during histopathological testing to investigate correlations of the mean
      displacement between the two CT scans and false-negative or true-positive biopsy
      results. For 11 patients, two PET scans were acquired; one at the beginning of
      the procedure, pre-needle insertion, and an additional one with the needle in
      place. The pre-insertion PET scan was corrected for intraprocedural motion by
      applying the DVF. The corrected PET was compared with the post-needle insertion
      PET to validate the correction method. RESULTS: The mean displacement of tissue
      around the needle between the pre-biopsy CT and the postneedle insertion CT was
      5.1 mm (min = 1.1 mm, max = 10.9 mm and SD = 3.0 mm). For mean displacements
      larger than 7.2 mm, the biopsy cores gave false-negative results. Correcting pre
      biopsy PET using the DVF improved the PET/CT registration in 8 of 11 cases.
      CONCLUSIONS: The DVF obtained from DIR of the CT scans can be used for evaluation
      and correction of the error in needle placement with respect to the FDG-avid
      area. Misregistration between the pre-biopsy PET and the CT acquired with the
      needle in place was shown to correlate with false negative biopsy results.

PMID- 28494090
TI  - Technical Note: Transconvolution based equalization of positron energy effects
      for the use of 68 Ge/68 Ga phantoms in determining 18 F PET recovery.
AB  - PURPOSE: Avoiding measurement variability from 18 F phantom preparation by using
      68 Ge/68 Ga phantoms for the determination of 18 F recovery curves (RC) in
      clinical quality assurance measurements and for PET/CT site qualification in
      multicentre clinical trials. METHODS: RCs were obtained from PET/CT measurements
      of seven differently sized phantom spheres filled either with 18 F or with 68 Ga.
      RCs for the respective other isotope were then determined by two different
      methods: In the first method, images were convolved with positron range
      transconvolution functions derived from positron annihilation distributions found
      in literature. This method generated recasted images matching images using the
      respective other isotope. In the second method, the PET/CT system's isotope
      independent (intrinsic) point spread function was determined from said phantom
      measurements and convolved with numerical representations simulating hot spheres
      filled with the respective other isotope. These simulations included the isotope
      specific positron annihilation distributions. Recovered activity concentrations
      were compared between recasted images, simulated images, and the originally
      acquired images. RESULTS: 18 F and 68 Ga recovery was successfully determined
      from image acquisitions of the respective opposite isotope as well as from the
      simulations. 68 Ga RCs derived from 18 F data had a normalized root-mean-square
      deviation (NRMSD) from real 68 Ga measurements of 0.019% when using the first
      method and of 0.008% when using the second method. 18 F RCs derived from 68 Ga
      data had a NRMSD from real 18 F measurements of 0.036% when using the first
      method and of 0.038% when using the second method. CONCLUSIONS: Applying the
      principles of transconvolution, 18 F RCs can be recalculated from 68 Ga phantom
      measurements with excellent accuracy. The maximal additionally introduced error
      was below 0.4% of the error currently accepted for RCs in the site qualification
      of multicentre clinical trials by the EARL program of the European Association of
      Nuclear Medicine (EANM). Therefore, our methods legitimately allow for the use of
      long-lived solid state 68 Ge/68 Ga phantoms instead of manually prepared 18 F
      phantoms to characterize comparability of 18 F measurements across different
      imaging sites or of longitudinal 18 F measurements at a single PET/CT system.

PMID- 28494092
TI  - Incidence of human cytomegalovirus infection and T-cell response in patients with
      psoriasis before and during antitumour necrosis factor-alpha therapy.

PMID- 28494091
TI  - Fermentation Characteristics and Aromatic Profile of Plum Wines Produced with
      Indigenous Microbiota and Pure Cultures of Selected Yeast.
AB  - The aim of this study was to assess and compare fermentation characteristics and
      aromatic profile of plum wines produced with indigenous microbiota and pure
      cultures of different selected yeast. Experiments were carried out with plum
      (Prunus domestica L.) varieties of different fruit ripening times (Cacanska rana,
      Cacanska lepotica, and Pozegaca). Wine fermentations were conducted by the
      activity of indigenous microbiota, commercially available Saccharomyces
      cerevisiae and Saccharomyces bayanus yeast strains and joint activity of
      Schizosaccharomyces pombe and S. cerevisiae (sequential inoculation).
      Statistically significant differences in fermentative characteristics and the
      content of certain volatile compounds were observed as a result of metabolic
      activity of various indigenous and/or selected yeasts during fermentation of plum
      pomace. Minimal duration of fermentation (4 to 5 d) and fastest ethanol
      production rate (from 12.3 to 15.5 g/L/d) were the characteristics of the studied
      S. cerevisiae strains. Isobutanol, 3-methyl-1-butanol, 1-heptanol, and 1-octanol
      were the most prevalent higher alcohols in the tested plum wine samples. The
      predominant ester in plum wines was ethyl acetate, ethyl lactate, amyl acetate,
      isoamyl acetate, and ethyl palmitate, esters responsible for the floral and
      fruity olfactory tones, were also present in large amounts. Also, the use of S.
      cerevisiae strains resulted in the production of plum wines with better sensory
      characteristics than ones produced with other investigated yeasts. Obtained
      results are significant since there is limited data on the compounds responsible
      for the unique flavor of plum wine, as well as on the impact of different yeast
      starter cultures application on the overall quality of fruit wines.

PMID- 28494093
TI  - Study on the Removal of Cadmium in Rice Using Microbial Fermentation Method.
AB  - This work mainly examined how to remove cadmium in rice by fermentation, the
      removal mechanisms, and the quality of fermented rice in order to utilize cadmium
      contaminated rice. The fermentation time, temperature, liquid ratio, inoculant
      levels, and number of washes were varied to optimize the efficiency of cadmium
      removal. The optimum fermentation process, in which the rate of cadmium removal
      from the rice is 80.84%, required an inoculant amount of 0.1%, a liquid ratio of
      1:1, a period of 60 h at 37  degrees C, and subsequently washed with water 4
      times. The physicochemical properties of raw cadmium-contaminated rice and
      fermented rice were studied. Results showed that the pasting temperature of the
      fermented rice became lower, and temperature at which pasting starts dropped but
      the endothermic enthalpy increased, implying that the protein content in the rice
      decreased during the fermentation. It suggested that the crystal structure of
      rice starch changed and fermentation did not result in the formation of new
      chemical bonds or functional groups in the rice. Microbial fermentation method
      can therefore effectively reduce cadmium level in contaminated rice.

PMID- 28494094
TI  - Effect of Different Extrusion Parameters on Dietary Fiber in Wheat Bran and Rye
      Bran.
AB  - Wheat bran and rye bran are mostly used as animal feed today, but their high
      content of dietary fiber and bioactive components are beneficial to human health.
      Increased use of bran as food raw material could therefore be desirable. However,
      bran mainly contains unextractable dietary fiber and deteriorates the sensory
      properties of products. Processing by extrusion could increase the extractability
      of dietary fiber and increase the sensory qualities of bran products. Wheat bran
      and rye bran were therefore extruded at different levels of moisture content,
      screw speed and temperature, in order to find the optimal setting for increased
      extractability of dietary fiber and positive sensory properties. A water content
      of 24% for wheat bran and 30% for rye bran, a screw speed of 400 rpm, and a
      temperature of 130  degrees C resulted in the highest extractability of total
      dietary fiber and arabinoxylan. Arabinoxylan extractability increased from 5.8%
      in wheat bran to 9.0% in extruded wheat bran at those settings, and from 14.6% to
      19.2% for rye bran. Total contents of dietary fiber and arabinoxylan were not
      affected by extrusion. Content of beta-glucan was also maintained during
      extrusion, while its molecular weight decreased slightly and extractability
      increased slightly. Extrusion at these settings is therefore a suitable process
      for increasing the use of wheat bran and rye bran as a food raw material.

PMID- 28494095
TI  - Comparison of 192 Ir, 169 Yb, and 60 Co high-dose rate brachytherapy sources for
      skin cancer treatment.
AB  - PURPOSE: To evaluate the possibility of utilizing the high-dose rate (HDR) 169 Yb
      and 60 Co sources, in addition to 192 Ir, for the treatment of skin malignancies
      with conical applicators. METHODS: Monte Carlo (MC) simulations were used to
      benchmark the dosimetric parameters of single 169 Yb (4140), 60 Co (Co0.A86), and
      192 Ir (mHDR-V2) brachytherapy sources in a water phantom and compared their
      results against published data. A standard conical tungsten alloy Leipzig-style
      applicator (Stand.Appl) was used for determination of the dose distributions at
      various depths with a single dwell position of the HDR sources. The HDR sources
      were modeled with its long axis parallel to the treatment plane within the
      opening section of the applicator. The source-to-surface distance (SSD) was 1.6
      cm, which included a 0.1 cm thick removable plastic end-cap used for clinical
      applications. The prescription depth was considered to be 0.3 cm in a water
      phantom following the definitions in the literature for this treatment technique.
      Dose distributions generated with the Stand.Appl and the 169 Yb and 60 Co sources
      have been compared with those of the 192 Ir source, for the same geometry. Then,
      applicator wall thickness for the 60 Co source was increased (doubled) in MC
      simulations in order to minimize the leakage dose and penumbra to levels that
      were comparable to that from the 192 Ir source. For each source-applicator
      combination, the optimized plastic end-cap dimensions were determined in order to
      avoid over-dosage to the skin surface. RESULTS: The normalized dose profiles at
      the prescription depth for the 169 Yb-Stand.Appl and the 60 Co-double-wall
      applicator were found to be similar to that of the 192 Ir-Stand.Appl, with
      differences < 2.5%. The percentage depth doses (PDD) for the 192 Ir-, 169 Yb- and
      60 Co-Stand.Appl were found to be comparable to the values with the 60 Co-double
      walled applicator, with differences < 1.7%. The applicator output-factors at the
      prescription depth were also comparable at 0.309, 0.316, and 0.298 (cGy/hU) for
      the 192 Ir-, 169 Yb-Stand.Appl, and 60 Co-double-wall applicators respectively.
      The leakage dose around the Stand.Appl for distance > 2 cm from the applicator
      surface was < 5% for 192 Ir, < 1% for 169 Yb, and < 18% for 60 Co relative to the
      prescription dose. However, using the double-walled applicator for the 60 Co
      source reduced the leakage dose to around 5% of the prescription dose, which is
      comparable with that of the 192 Ir source. The optimized end-cap thicknesses for
      the 192 Ir-, 169 Yb-Stand.Appl, and the 60 Co-double-wall applicator were found
      to be 1.1, 0.6, and 3.7 mm respectively. CONCLUSIONS: Application of the 169 Yb
      (with Stand.Appl) or the 60 Co source (with double-wall applicator) has been
      evaluated as alternatives to the existing 192 Ir source (with Stand.Appl) for the
      HDR brachytherapy of skin cancer patients. These alternatives enable the clinics
      that may have 169 Yb or 60 Co sources instead of the 192 Ir source to perform the
      skin brachytherapy and achieve comparable results. The conical surface
      applicators must be used with a protective plastic end-cap to eliminate the
      excess electrons that are created in the source and applicator, in order to avoid
      skin surface over-dosage. The treatment times for the 60 Co source remain to be
      determined. Additionally, for 169 Yb, the source needs to be changed on monthly
      basis due to its limited half-life.

PMID- 28494096
TI  - Physicochemical Properties and Antioxidant Capacity of Chinese Olive (Canarium
      album L.) Cultivars.
AB  - In this study, the physicochemical characteristics and antioxidant potentials of
      10 Chinese olive cultivars were investigated. Considerable differences were found
      between cultivars in weight, edible yield, water content, size, shape, total
      soluble solids, and total titratable acidity. The major sugars and organic acids
      in all the cultivars were glucose, fructose, and malic acid. Phenolics were the
      most abundant antioxidants (1174.0 to 1799.6 mg gallic acid equivalents/100 g
      fresh weight). Twelve phenolic compounds were identified and quantified by UPLC
      MS/MS. Six compounds were identified first in the Chinese olive, with 3-O
      galloylquinic acid and geraniin isomers as the most abundant compounds. The
      results also indicated that the phenolic content (TPC) correlated with the
      antioxidant properties of Chinese olive fruit extracts. A principal component
      analysis indicated that the Tantou and Tanxiang cultivars were a valuable source,
      with high TPC and antioxidant activity, whereas Maken22, Changying, and Green
      changying cultivars may be eaten fresh and had high sugar and low phenolic
      contents. This information will be useful for selecting suitable cultivars for
      industry and the market.

PMID- 28494097
TI  - An open, multicentre, randomized clinical study in patients with bullous
      pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone
      and dapsone.
AB  - BACKGROUND: Current treatment of bullous pemphigoid (BP) is based on the long
      term use of topical and/or systemic corticosteroids, which are associated with a
      high rate of adverse events and increased mortality. OBJECTIVES: To study the
      corticosteroid-sparing potential of azathioprine and dapsone. METHODS: This was a
      prospective, multicentre, randomized, nonblinded clinical trial that compared the
      efficacy and safety of two parallel groups of patients with BP treated with oral
      methylprednisolone 0.5 mg kg-1 per day in combination with either azathioprine
      1.5-2.5 mg kg-1 per day or dapsone 1.5 mg kg-1 per day. Nine German and Austrian
      departments of dermatology included 54 patients based on clinical lesions,
      positive direct immunofluorescence (IF) microscopy and detection of serum
      autoantibodies by indirect IF microscopy, immunoblotting or enzyme-linked
      immunosorbent assay. The primary end point was the time until complete tapering
      of methylprednisolone, and the most important secondary end point was the
      cumulative corticosteroid dose. RESULTS: In eight patients (five azathioprine,
      three dapsone), methylprednisolone could be discontinued after a median time of
      251 days in the azathioprine group and 81 days in the dapsone group. The median
      cumulative corticosteroid dose was 2.65 g for azathioprine compared with 1.92 g
      for dapsone (P = 0.06). The median numbers of days when corticosteroids were
      applied were 148 and 51, respectively (P = 0.24). No significant difference in
      the number of adverse events was seen between the treatment arms. Four patients
      (8%) died within the observation period of 12 months. CONCLUSIONS: Due to the
      lower than intended number of patients, the results of the primary and secondary
      end points were not or only barely significant. Dapsone appeared to have a
      moderately higher corticosteroid-sparing potential than azathioprine. The
      combination regimen of either drug with oral methylprednisolone is associated
      with a relatively low 1-year mortality in this vulnerable patient population.

PMID- 28494098
TI  - Core elements to understand and improve coping with Parkinson's disease in
      patients and family carers: A focus group study.
AB  - AIMS: The aim of this study were: (1) To explore the meaning that coping with
      Parkinson's disease has for patients and family carers; (2) To suggest the
      components of an intervention focused on enhancing their coping with the disease.
      BACKGROUND: Adapting to Parkinson's disease involves going through many difficult
      changes; however, it may improve quality of life in patients and family carers.
      One of the key aspects for facilitating the psychosocial adjustment to
      Parkinson's disease is the strengthening of coping skills. DESIGN: A sequential
      explanatory mixed methods study was carried out. Findings from the qualitative
      phase are presented. METHODS: Data were collected in May 2014 through three focus
      groups: one of people with Parkinson's disease (n = 9), one of family carers (n =
      7) and one of healthcare professionals (n = 5). All focus groups were digitally
      recorded and transcribed verbatim and content analysis was independently carried
      out by two researchers. FINDINGS: The participants coincided in highlighting that
      coping with Parkinson's disease helped the patient and the family carer in their
      search for balance; and it implied a transformation in their lives. To aid the
      process of coping with Parkinson's disease, a multifaceted intervention is
      proposed. CONCLUSION: Coping with Parkinson's disease is a complex process for
      both patients and family carers and it should therefore be considered a standard
      service in healthcare policies aimed at this group. The proposed intervention
      constitutes a nursing tool which has great potential to improve the quality of
      life in Parkinson's disease and in other long-term conditions.

PMID- 28494099
TI  - Prevalence of gestational diabetes mellitus evaluated by universal screening with
      a 75-g, 2-hour oral glucose tolerance test and IADPSG criteria.
AB  - OBJECTIVE: To determine the prevalence of gestational diabetes mellitus (GDM) and
      its association with maternal age among Turkish women diagnosed by International
      Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. METHODS: A
      cross-sectional study was conducted in 2013-2015 among non-diabetic pregnant
      women aged 18-49 years who were universally screened for GDM by IADPSG criteria.
      The percentage of women meeting each diagnostic threshold and the prevalence of
      GDM by age group were calculated. Linear trends were evaluated by logistic
      regression. RESULTS: Among 1434 women screened, 159 (11.1%, 95% confidence
      interval 9.5%-12.7%) were diagnosed with GDM; eleven of these women had been
      diagnosed according to a fasting glucose level in the first trimester. The
      prevalence of GDM was 6.6% (10/151), 7.3% (37/507), 8.8% (42/479), 16.7%
      (45/270), and 35.2% (25/71) among women aged younger than 25, 25-29, 30-34, 35
      39, and 40 years or older, respectively. GDM prevalence increased with age
      (P<0.001). The numbers of women diagnosed with GDM in the second trimester who
      exceeded one, two, and three thresholds of the 2-hour oral glucose tolerance test
      were 66 (44.6%), 52 (35.1%), and 30 (20.3%), respectively. CONCLUSION: Prevalence
      of GDM was correlated with maternal age. Most women diagnosed in the second
      trimester exceeded the threshold at only one of the three timepoints.

PMID- 28494100
TI  - Paracrine regulation of melanogenesis.
AB  - Melanocytes are generally characterized by the basic ability of melanin synthesis
      and transfer to adjacent keratinocytes. This constitutes an individual skin
      phenotype and provides epidermal protection from various stimuli, such as
      ultraviolet irradiation, through a complex process called melanogenesis, which
      can be regulated by autocrine or paracrine factors. Recent evidence has revealed
      the paracrine effects of keratinocytes on melanogenesis by secreting cytokines,
      including alpha-melanocyte stimulating hormone and endothelin-1. In addition to
      keratinocytes, there are other types of cells in the skin, such as fibroblasts
      and immune cells, which are also actively involved in the regulation of
      melanocyte behaviour through the production of paracrine factors. In addition,
      extracellular matrix proteins, which are secreted mainly by skin-resident cells,
      not only play direct roles in regulating melanocyte morphology and functions but
      also provide structural support between the epidermis and dermis to control the
      distribution of various secreted cytokines from keratinocytes and/or fibroblasts,
      which are potentially involved in the regulation of melanogenesis. Moreover,
      understanding the origin of melanocytes (neural crest cells) and the presence of
      nerve endings in the epidermis can reveal the intimate contact between
      melanocytes and cutaneous specific nervous system proteins. Melanocytes are
      associated with all these networks with corresponding receptors expressed on the
      cell surface. In this review, we provide an overview of recent advances in
      determining the intimate relationships between melanocytes and their surrounding
      elements, which provide insights into the complex nature of the regulation of
      melanogenesis.

PMID- 28494101
TI  - Stability Enhancement of Ocimum Sanctum Linn. Essential Oils Using Stearic Acid
      in Aluminum Carboxymethyl Cellulose Film-Coated Gelatin Microcapsules.
AB  - Holy basil essential oils (HBEO) can be used in many food applications due to
      antioxidant and antimicrobial attributes, but they are susceptible to degradation
      upon storage. Therefore, a protective system is required to extend their shelf
      life. HBEO was microencapsulated by coacervation using gelatin and the
      microcapsules were subsequently coated with stearic acid (1%, 2%, and 3%) in
      carboxymethyl cellulose emulsions. The results showed that HBEO contents
      decreased with increasing stearic acid concentrations from 76% to 59%. Fourier
      transform infrared spectroscopy analysis suggested that HBEO was stable during
      microencapsulation. After 3-month storage, changes in appearance were detected in
      all samples, especially the uncoated and 3% stearic acid-coated microcapsules.
      Additionally, the surface HBEO content increased significantly, consistent with a
      distinct increase in darkness and agglomeration. X-ray diffraction analysis
      revealed the physical change of microcapsules, attributed to the renaturation of
      gelatin and recrystallization of stearic acid. The antioxidant activity of both
      non-encapsulated and encapsulated HBEO after storage decreased significantly,
      except the microcapsule coated with 1% stearic acid (half maximal inhibitory
      concentration of 0.35 mg/mL), whereas the antimicrobial activity remained
      constant. The findings suggest that HBEO microcapsules coated with 1% stearic
      acid could serve as antioxidant and antimicrobial additives in food industries.

PMID- 28494102
TI  - Noninvasive carotid artery elastography using multielement synthetic aperture
      imaging: Phantom and in vivo evaluation.
AB  - PURPOSE: Vascular elastography can visualize the strain distribution in the
      carotid artery, which could be useful in assessing the propensity of advanced
      plaques to rupture. In our previous studies, we demonstrated that sparse
      synthetic aperture (SA) imaging can produce high quality vascular strain
      elastograms. However, the low output power of SA imaging may hamper its clinical
      utility. In this study, we hypothesize that multi-element defocused emissions can
      overcome this limitation and improve the quality of the vascular strain
      elastograms. METHODS: To assess the impact of attenuation on the elastographic
      performance of SA and (multi-element synthetic aperture) MSA imaging, we
      conducted experiments using heterogeneous vessel phantoms with ideal (0.1 dB cm-1
      MHz-1 ) and realistic (0.75 dB cm-1 MHz-1 ) attenuation. Further, we validated
      the results of the phantom study in vivo, on a healthy male volunteer. All echo
      imaging was performed at a transmit frequency of 5 MHz, using a commercially
      available ultrasound scanner (Sonix RP, Ultrasonix Medical Corp., Richmond, BC,
      Canada). RESULTS: The results from the phantom results demonstrated that plaques
      were visible in all strain elastograms, but those produced using MSA imaging had
      less artifacts. MSA imaging improved the elastographic contrast to noise ratio
      (CNRe) of the vascular elastograms by 14.58 dB relative to SA imaging, and 9.1 dB
      relative to compounded plane wave (CPW) imaging. Further, the results
      demonstrated that the elastographic performance of MSA imaging improved with
      increase in (a) the number of transmit-receive events and (b) the size of the
      transmit sub-aperture, up to 13 elements. Using larger sub-apertures degraded the
      elastographic performance. The results from the in vivo study were in good
      agreement with the phantom results. Specifically, using a defocused multi-element
      transmit sub-aperture for SA imaging improved the performance of vascular
      elastography. CONCLUSIONS: The results suggested that MSA imaging can produce
      reliable vascular stain elastograms. Future studies will involve using coded
      excitations to improve the CNRe and frame-rate of the proposed technique for
      vascular elastography.

PMID- 28494103
TI  - Recruiting nurses through social media: Effects on employer brand and
      attractiveness.
AB  - AIM: To investigate whether and how nurses' exposure to a hospital's profile on
      social media affects their perceptions of the hospital's brand and attractiveness
      as an employer. BACKGROUND: Since in many places across the globe hospitals are
      struggling with nursing shortages, competition is rising to be perceived as an
      attractive employer by this target group. Organizations are increasingly using
      social media for recruitment, however, little is known about its effects on
      potential applicants' perceptions of the organization as an employer. We thus
      examine whether these effects occur and rely on the media richness theory to
      explain the mechanisms at play. DESIGN: A between-subjects experimental design
      was applied. Three conditions were used: a control group, one condition that
      required visiting the Facebook page of a hospital and one condition that required
      visiting the LinkedIn page. METHOD: The focal organization was an existing
      Belgian hospital which had a LinkedIn and a Facebook page. An online
      questionnaire was sent to nursing students and employed nurses over 5 months in
      2015-2016. RESULTS: Nurses' exposure to the hospital's Facebook or LinkedIn page
      had a significant positive effect on a majority of the employer brand dimensions,
      both instrumental and symbolic. In addition, nurses who visited the Facebook page
      felt more attracted to working at the hospital. Most of these effects were
      mediated by social presence. CONCLUSION: Nurses' perceptions of employers can be
      positively influenced by seeing a hospital's social media page. Hospitals can
      thus employ social media to improve their employer brand image and
      attractiveness.

PMID- 28494104
TI  - Prevalence of metabolic syndrome and its association with lifestyle and
      cardiovascular biomarkers among postmenopausal women in western Algeria.
AB  - OBJECTIVE: To evaluate the prevalence of metabolic syndrome (MetS), its
      components, and their relationship with lifestyle, inflammation, and oxidative
      stress among postmenopausal Algerian women. METHODS: A prospective cross
      sectional survey was conducted among postmenopausal women at a clinic in Oran,
      Algeria, from March 1 to June 28, 2015. A diagnosis of MetS was made using the
      National Cholesterol Education Program Adult Treatment Panel III guidelines.
      Demographic, clinical, metabolic, inflammatory, dietary, and energy variables
      were assessed. RESULTS: Among 183 participants, 106 (57.9%) were diagnosed with
      MetS. Components of MetS included hypertension (n=144, 78.7%), hyperglycemia
      (n=135, 73.8%), hypertriglyceridemia (n=125, 68.3%), abdominal obesity (n=123,
      67.2%), and low levels of high-density lipoprotein cholesterol (n=121, 66.1%).
      Although daily energy expenditure was similar among the women with or without
      MetS, total energy intake was increased in the group with MetS (P<0.001). The
      following measures were also increased among women with MetS: saturated fatty
      acid intake (P<0.001), C-reactive protein (P=0.051), thiobarbituric acid reactive
      substances (P<0.001), and carbonyls (P<0.001). By contrast, decreased
      monounsaturated fatty acid intake (P=0.024) and catalase activity (P<0.001) were
      observed in this group. CONCLUSION: Postmenopausal status could predict MetS,
      with inflammation and oxidative stress arising from an unhealthy lifestyle
      potentially increasing cardiovascular risk.

PMID- 28494105
TI  - Empathy in paediatric intensive care nurses part 2: Neural correlates.
AB  - AIMS: To determine if there are brain activity differences between paediatric
      intensive care nurses and allied health professionals during pain intensity
      rating tasks and test whether these differences are related to the population
      observed (infant or adult) and professional experience. BACKGROUND: The
      underestimation of patients' pain by healthcare professionals has generally been
      associated with patterns of change in neural response to vicarious pain, notably
      reduced activation in regions associated with affective sharing and increased
      activation in regions associated with regulation, compared with controls.
      Paediatric nurses, however, have recently been found to provide higher estimates
      of infants' pain in comparison to allied health controls, suggesting that changes
      in neural response of this population might be different than other health
      professionals. DESIGN: Cross-sectional study. METHODS: Functional MRI data were
      acquired from September 2014-June 2015 and used to compare changes in brain
      activity in 27 female paediatric care nurses and 24 allied health professionals
      while rating the pain of infants and adults in a series of video clips. RESULTS:
      Paediatric nurses rated infant and adult pain higher than allied health
      professionals, but the two groups' neural response only differed during
      observation of infant pain; paediatric nurses mainly showed significantly less
      activation in the medial prefrontal cortex (linked to cognitive empathy) and in
      the left anterior insula and inferior frontal cortex (linked to affective
      sharing). CONCLUSIONS: Patterns of neural activity to vicarious pain may vary
      across healthcare professions and patient populations and the amount of
      professional experience might explain part of these differences.

PMID- 28494106
TI  - Closed-loop control of compression paddle motion to reduce blurring in
      mammograms.
AB  - BACKGROUND: Since the introduction of full field digital mammography (FFDM) a
      large number of UK breast cancer screening centers have reported blurred images,
      which can be caused by movement at the compression paddle during image
      acquisition. PURPOSE: To propose and investigate the use of position feedback
      from the breast side of the compression paddle to reduce the settling time of
      breast side motion. METHOD: Movement at the breast side of the paddle was
      measured using two calibrated linear potentiometers. A mathematical model for the
      compression paddle, machine drive, and breast was developed using the paddle
      movement data. Simulation software was used to optimize the position feedback
      controller parameters for different machine drive time constants and simulate the
      potential performance of the proposed system. RESULTS: The results obtained are
      based on simulation alone and indicate that closed-loop control of breast side
      paddle position dramatically reduced the settling time from over 90 s to less
      than 4 s. The effect of different machine drive time constants on the open-loop
      response is insignificant. With closed-loop control, the larger the time constant
      the longer the time required for the breast side motion to settle. CONCLUSIONS:
      Paddle motion induced blur could be significantly reduced by implementing the
      proposed closed-loop control.

PMID- 28494107
TI  - Recommendation to test limonene hydroperoxides 0.3% and linalool hydroperoxides
      1.0% in the British baseline patch test series.
AB  - BACKGROUND: There is a significant rate of sensitization worldwide to the
      oxidized fragrance terpenes limonene and linalool. Patch testing to oxidized
      terpenes is not routinely carried out; the ideal patch test concentration is
      unknown. OBJECTIVES: To determine the best test concentrations for limonene and
      linalool hydroperoxides, added to the British baseline patch test series, to
      optimize detection of true allergy and to minimize irritant reactions. METHODS:
      During 2013-2014, 4563 consecutive patients in 12 U.K. centres were tested to
      hydroperoxides of limonene in petrolatum (pet.) 0.3%, 0.2% and 0.1%, and
      hydroperoxides of linalool 1.0%, 0.5% and 0.25% pet. Irritant reactions were
      recorded separately from doubtful reactions. Concomitant reactions to other
      fragrance markers and clinical relevance were documented. RESULTS: Limonene
      hydroperoxide 0.3% gave positive reactions in 241 (5.3%) patients, irritant
      reactions in 93 (2.0%) and doubtful reactions in 110 (2.4%). Linalool
      hydroperoxide 1.0% gave positive reactions in 352 (7.7%), irritant reactions in
      178 (3.9%) and doubtful reactions in 132 (2.9%). A total of 119 patients with
      crescendo reactions to 0.3% limonene would have been missed if only tested with
      0.1% and 131 patients with crescendo reactions to 1.0% linalool would have been
      missed if only tested with 0.25%. In almost two-thirds of patients with positive
      patch tests to limonene and linalool the reaction was clinically relevant. The
      majority of patients did not react to any fragrance marker in the baseline
      series. CONCLUSIONS: We recommend that limonene hydroperoxides be tested at 0.3%
      and linalool hydroperoxides at 1.0% in the British baseline patch test series.

PMID- 28494109
TI  - Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the
      Literature.
AB  - Gilbert syndrome (GS) is a hereditary condition that affects ~10% of the
      population. It is characterized by intermittent, unconjugated hyperbilirubinemia
      in the absence of hepatocellular damage and hemolysis. Although GS is often
      described as a benign laboratory finding, it may alter drug metabolism by
      decreasing the ability to conjugate drugs. Genetic polymorphisms, specifically
      the UGT1A1*28 allele, may reduce glucuronidation by 30% that severely impacts the
      ability to metabolize certain medications. Antineoplastic agents used in
      oncologic settings have toxic side effects, and alterations in metabolism may
      result in severe or even life-threatening toxicities. Many of the drug monographs
      provided by manufacturers contain dose adjustment parameters for hepatic
      function, using serum bilirubin as a surrogate marker. However, in patients with
      GS, hepatic function remains normal in the setting of hyperbilirubinemia, and
      scant literature is available to provide guidance on empirical dosage adjustment.
      In this review, we conducted a literature search of routinely used oncology
      medications and assessed the need for empirical dose adjustments in the setting
      of GS.

PMID- 28494110
TI  - Computerized detection of lung nodules through radiomics.
AB  - PURPOSE: Lung cancer is a major cause of cancer deaths, and the 5-year survival
      rate of stage IV lung cancer patients is only 2%. However, the 5-year survival
      rate of stage I lung cancer patients significantly increases to 50%. As such,
      spiral computed tomography (CT) scans are necessary to diagnose high-risk lung
      cancer patients in early stages. In this study, a computer-aided detection (CAD)
      system with radiomics was proposed. This system could automatically detect
      pulmonary nodules and reduce radiologists' workloads and human errors. METHODS:
      In the proposed scheme, a nodular enhancement filter was used to segment nodule
      candidates and extract radiomic features. A synthetic minority over-sampling
      technique was also applied to balance the samples, and a random forest method was
      utilized to distinguish between real nodules and false positive detections. The
      radiomics approach quantified intratumor heterogeneity and multifrequency
      information, which are highly correlated with lung nodules. RESULTS: The proposed
      method was used to evaluate 1004 CT cases from the well-known Lung Image Database
      Consortium, and 88.9% sensitivity with four false positive detections per CT scan
      was obtained by randomly selecting 502 cases for training and 502 other cases for
      testing. CONCLUSIONS: The proposed scheme yielded a high performance on the LIDC
      database. Therefore, the proposed scheme is possibly effective for various CT
      configurations used in routine diagnosis and lung cancer screening.

PMID- 28494108
TI  - Selective kappa receptor partial agonist HS666 produces potent antinociception
      without inducing aversion after i.c.v. administration in mice.
AB  - BACKGROUND AND PURPOSE: The kappa receptor has a central role in modulating
      neurotransmission in central and peripheral neuronal circuits that subserve pain
      and other behavioural responses. Although kappa receptor agonists do not produce
      euphoria or lead to respiratory suppression, they induce dysphoria and sedation.
      We hypothesized that brain-penetrant kappa receptor ligands possessing biased
      agonism towards G protein signalling over beta-arrestin2 recruitment would
      produce robust antinociception with fewer associated liabilities. EXPERIMENTAL
      APPROACH: Two new diphenethylamines with high kappa receptor selectivity, HS665
      and HS666, were assessed following i.c.v. administration in mouse assays of
      antinociception with the 55 degrees C warm-water tail withdrawal test, locomotor
      activity in the rotorod and conditioned place preference. The [35 S]-GTPgammaS
      binding and beta-arrestin2 recruitment in vitro assays were used to characterize
      biased agonism. KEY RESULTS: HS665 (kappa receptor agonist) and HS666 (kappa
      receptor partial agonist) demonstrated dose-dependent antinociception after
      i.c.v. administration mediated by the kappa receptor. These highly selective
      kappa receptor ligands displayed varying biased signalling towards G protein
      coupling in vitro, consistent with a reduced liability profile, reflected by
      reduced sedation and absence of conditioned place aversion for HS666. CONCLUSIONS
      AND IMPLICATIONS: HS665 and HS666 activate central kappa receptors to produce
      potent antinociception, with HS666 displaying pharmacological characteristics of
      a kappa receptor analgesic with reduced liability for aversive effects
      correlating with its low efficacy in the beta-arrestin2 signalling pathway. Our
      data provide further understanding of the contribution of central kappa receptors
      in pain suppression, and the prospect of dissociating the antinociceptive effects
      of HS665 and HS666 from kappa receptor-mediated adverse effects.

PMID- 28494111
TI  - Evaluation of indicated non-cosmetic panniculectomy at time of gynecologic
      surgery.
AB  - OBJECTIVE: To report postoperative outcomes among patients undergoing indicated
      non-cosmetic panniculectomy at the time of gynecologic surgery. METHODS: Medical
      charts were retrospectively reviewed for patients who underwent panniculectomy
      coupled with gynecologic surgery at a university-affiliated hospital in the USA
      in 1990-2014. The data reviewed included age, body mass index (BMI, calculated as
      weight in kilograms divided by the square of height in meters), surgical
      procedure, estimated blood loss, pathology, wound complication, diabetes,
      hypertension, smoking, and readmission rate. One-way analysis of variance and
      logistic regression were used to evaluate the data. RESULTS: In total, 300
      patients underwent panniculectomy; the mean age was 51 years and the mean BMI was
      46. Overall, there were 94 (31.3%) complications, including 85 (28.3%) cases of
      superficial cellulitis and 9 (3.0%) cases of surgical-site infection. In logistic
      regression, diabetes, hypertension, and smoking were significant predictors of
      wound complications, identifying 78% of women who subsequently developed wound
      complications. CONCLUSION: Panniculectomy combined with gynecologic surgery was
      found to be safe and effective for obese patients, with an acceptable incidence
      of wound infection. History of diabetes, hypertension, and smoking increased the
      risk of postoperative wound complications. These factors will help to predict
      patients at risk of wound complication.

PMID- 28494113
TI  - The diagnostic conundrum of bacterial infections in cirrhotic patients.

PMID- 28494112
TI  - Using the Lewis Acid Me3 Si-F-Al(ORF )3 To Prepare Phosphino-Phosphonium Cations
      with the Least-Coordinating Anion [(RF O)3 Al-F-Al(ORF )3 ].
AB  - By reaction of two equivalents of Me3 Si-F-Al(ORF )3 1 with an equimolar amount
      of PPh2 Cl, the salt [Ph2 P-PPh2 Cl]+ [(RF O)3 Al-F-Al(ORF )3 ]- 2 is prepared
      smoothly in 91 % yield (NMR, XRD). The synthesis of [Ph2 P-PPh3 ]+ [(RF O)3 Al-F
      Al(ORF )3 ]- 3 is best achieved by a two-step reaction: first, two equivalents of
      1 react with one PPh3 to give [Me3 Si-PPh3 ]+ [(RF O)3 Al-F-Al(ORF )3 ]- 4 (NMR,
      XRD), which, upon reaction with PPh2 Cl, yields pure 3 and Me3 SiCl (NMR, XRD).
      Typically, a stoichiometry of two equivalents of 1 with respect to one equivalent
      of the chloride donor should be used. Otherwise, the residual strong Lewis
      acidity of the [(RF O)3 Al-F-Al(ORF )3 ]- anion in the presence of the [F-Al(ORF
      )3 ]- anion-that forms with less than two equivalents of 1-leads to further
      chloride exchange reactions that complicate work-up. This route presents the
      easiest way to introduce the least-coordinating [(RF O)3 Al-F-Al(ORF )3 ]- anion
      into a system. We expect a wide use of this route in all areas, in which chloride
      bond heterolysis in combination with very weakly coordinating anions is
      desirable. Additionally, we performed calculations on the bond dissociation
      mechanisms of [R2 P-PMe3 ]+ and the isoelectronic Me2 P-SiMe3 and Me2 Si-PMe3 in
      dependence of the solvent permittivity. These calculations show, especially for
      the neutral reference compounds, a heavy influence of the solvent on the
      dissociation mechanism, which is why we suggest investigating these properties in
      solution instead of gas phase.

PMID- 28494114
TI  - A Sustainable Redox-Flow Battery with an Aluminum-Based, Deep-Eutectic-Solvent
      Anolyte.
AB  - Nonaqueous redox-flow batteries are an emerging energy storage technology for
      grid storage systems, but the development of anolytes has lagged far behind that
      of catholytes due to the major limitations of the redox species, which exhibit
      relatively low solubility and inadequate redox potentials. Herein, an aluminum
      based deep-eutectic-solvent is investigated as an anolyte for redox-flow
      batteries. The aluminum-based deep-eutectic solvent demonstrated a significantly
      enhanced concentration of circa 3.2 m in the anolyte and a relatively low redox
      potential of 2.2 V vs. Li+ /Li. The electrochemical measurements highlight that a
      reversible volumetric capacity of 145 Ah L-1 and an energy density of 189 Wh L-1
      or 165 Wh kg-1 have been achieved when coupled with a I3- /I- catholyte. The
      prototype cell has also been extended to the use of a Br2 -based catholyte,
      exhibiting a higher cell voltage with a theoretical energy density of over 200 Wh
      L-1 . The synergy of highly abundant, dendrite-free, multi-electron-reaction
      aluminum anodes and environmentally benign deep-eutectic-solvent anolytes reveals
      great potential towards cost-effective, sustainable redox-flow batteries.

PMID- 28494115
TI  - Disentangling species and functional group richness effects on soil N cycling in
      a grassland ecosystem.
AB  - Species richness (SR) and functional group richness (FGR) are often confounded in
      both observational and experimental field studies of biodiversity and ecosystem
      function. This precludes discernment of their separate influences on ecosystem
      processes, including nitrogen (N) cycling, and how those influences might be
      moderated by global change factors. In a 17-year field study of grassland
      species, we used two full factorial experiments to independently vary SR (one or
      four species, with FGR = 1) and FGR (1-4 groups, with SR = 4) to assess SR and
      FGR effects on ecosystem N cycling and its response to elevated carbon dioxide
      (CO2 ) and N addition. We hypothesized that increased plant diversity (either SR
      or FGR) and elevated CO2 would enhance plant N pools because of greater plant N
      uptake, but decrease soil N cycling rates because of greater soil carbon inputs
      and microbial N immobilization. In partial support of these hypotheses,
      increasing SR or FGR (holding the other constant) enhanced total plant N pools
      and decreased soil nitrate pools, largely through higher root biomass, and
      increasing FGR strongly reduced mineralization rates, because of lower root N
      concentrations. In contrast, increasing SR (holding FGR constant and despite
      increasing total plant C and N pools) did not alter root N concentrations or net
      N mineralization rates. Elevated CO2 had minimal effects on plant and soil N
      metrics and their responses to plant diversity, whereas enriched N increased
      plant and soil N pools, but not soil N fluxes. These results show that functional
      diversity had additional effects on both plant N pools and rates of soil N
      cycling that were independent of those of species richness.

PMID- 28494116
TI  - Randomised clinical study of plaque removal efficacy of a power toothbrush in a
      paediatric population.
AB  - BACKGROUND: Clinical investigations of plaque removal efficacy of power
      toothbrushes in children are limited. AIM: To compare plaque removal of a power
      versus manual toothbrush in a paediatric population. DESIGN: This was a
      randomised, replicate-use, single-brushing, examiner-blinded, two-treatment, four
      period crossover clinical trial in children 8-11 years of age. Subjects were
      randomly assigned to a treatment sequence involving an oscillating-rotating power
      toothbrush and a manual toothbrush control. Subjects brushed under supervision
      with a NaF dentifrice. Plaque was assessed pre- (baseline) and post-brushing
      using the Turesky Modification of the Quigley-Hein Plaque Index by two examiners.
      Plaque scores were averaged for mixed and permanent dentition on a per-subject
      basis and analysed using a mixed-model ancova for a crossover design. RESULTS:
      Forty-one subjects (mean 9.0 years) were randomised and completed the trial. Both
      the power brush and manual brush provided statistically significant mean plaque
      reductions versus baseline in all analyses (P < 0.001). For both examiners,
      plaque removal was significantly (P < 0.001) larger for the power brush in
      permanent and mixed dentitions. The interexaminer correlations for the permanent
      dentition were strong (ICC = 0.68-0.88) for pre-brushing plaque across all
      periods. CONCLUSIONS: An oscillating-rotating power toothbrush provided superior
      plaque reduction versus a manual toothbrush in children.

PMID- 28494117
TI  - Something old, something new, something borrowed, something green.

PMID- 28494118
TI  - Objective automated quantification of fluorescence signal in histological
      sections of rat lens.
AB  - Visual quantification and classification of fluorescent signals is the gold
      standard in microscopy. The purpose of this study was to develop an automated
      method to delineate cells and to quantify expression of fluorescent signal of
      biomarkers in each nucleus and cytoplasm of lens epithelial cells in a
      histological section. A region of interest representing the lens epithelium was
      manually demarcated in each input image. Thereafter, individual cell nuclei
      within the region of interest were automatically delineated based on watershed
      segmentation and thresholding with an algorithm developed in MatlabTM.
      Fluorescence signal was quantified within nuclei, cytoplasms and juxtaposed
      backgrounds. The classification of cells as labelled or not labelled was based on
      comparison of the fluorescence signal within cells with local background. The
      classification rule was thereafter optimized as compared with visual
      classification of a limited dataset. The performance of the automated
      classification was evaluated by asking 11 independent blinded observers to
      classify all cells (n = 395) in one lens image. Time consumed by the automatic
      algorithm and visual classification of cells was recorded. On an average, 77% of
      the cells were correctly classified as compared with the majority vote of the
      visual observers. The average agreement among visual observers was 83%. However,
      variation among visual observers was high, and agreement between two visual
      observers was as low as 71% in the worst case. Automated classification was on
      average 10 times faster than visual scoring. The presented method enables
      objective and fast detection of lens epithelial cells and quantification of
      expression of fluorescent signal with an accuracy comparable with the variability
      among visual observers. (c) 2017 International Society for Advancement of
      Cytometry.

PMID- 28494119
TI  - Noncovalent Interactions between Dopamine and Regular and Defective Graphene.
AB  - The role of noncovalent interactions in the adsorption of biological molecules on
      graphene is a subject of fundamental interest regarding the use of graphene as a
      material for sensing and drug delivery. The adsorption of dopamine on regular
      graphene and graphene with monovacancies (GV) is theoretically studied within the
      framework of density functional theory. Several adsorption modes are considered,
      and notably those in which the dopamine molecule is oriented parallel or quasi
      parallel to the surface are the more stable. The adsorption of dopamine on
      graphene implies an attractive interaction of a dispersive nature that competes
      with Pauli repulsion between the occupied pi orbitals of the dopamine ring and
      the pi orbitals of graphene. If dopamine adsorbs at the monovacancy in the A-B
      stacking mode, a hydrogen bond is produced between one of the dopamine hydroxy
      groups and one carbon atom around the vacancy. The electronic charge
      redistribution due to adsorption is consistent with an electronic drift from the
      graphene or GV surface to the dopamine molecule.

PMID- 28494121
TI  - Biomimetic Total Synthesis of (+/-)-Homodimericin A.
AB  - A biomimetic total synthesis of racemic homodimericin A was achieved in seven
      steps, including two cascade reactions. Aqueous buffer solutions are found to
      help both the oxidative dimerization cascade and the intramolecular Diels-Alder
      cascade. This synthetic sequence validates key steps in the biogenetic proposal
      of homodimericin A.

PMID- 28494120
TI  - Posttraumatic stress disorder symptom severity is associated with reduced default
      mode network connectivity in individuals with elevated genetic risk for
      psychopathology.
AB  - BACKGROUND: Accumulating evidence suggests that posttraumatic stress disorder
      (PTSD) is associated with disrupted default mode network (DMN) connectivity, but
      findings across studies have not been uniform. Individual differences in relevant
      genes may account for some of the reported variability in the relationship
      between DMN connectivity and PTSD. In this study, we investigated this
      possibility using genome-wide association study (GWAS) derived polygenic risk
      scores (PRSs) for relevant psychiatric traits. We hypothesized that the
      association between PTSD and DMN connectivity would be moderated by genetic risk
      for one or more psychiatric traits such that individuals with elevated polygenic
      risk for psychopathology and severe PTSD would exhibit disrupted DMN
      connectivity. METHODS: Participants were 156 white, non-Hispanic veterans of the
      wars in Iraq and Afghanistan who were genotyped and underwent resting state
      functional magnetic resonance imaging and clinical assessment. PRSs for
      neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based
      on five psychiatric disorders) were calculated using summary statistics from
      published large-scale consortia-based GWASs. RESULTS: Cross-disorder polygenic
      risk influenced the relationship between DMN connectivity and PTSD symptom
      severity such that individuals at greater genetic risk showed a significant
      negative association between PTSD symptom severity and connectivity between the
      posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for
      neuroticism, anxiety, and major depressive disorder did not influence DMN
      connectivity directly or through an interaction with PTSD. CONCLUSIONS: Findings
      illustrate the potential power of genome-wide PRSs to advance understanding of
      the relationship between PTSD and DMN connectivity, a putative neural
      endophenotype of the disorder.

PMID- 28494122
TI  - Comprehensive database of Manufactured Gas Plant tars. Part B. Aliphatic and
      aromatic compounds.
AB  - RATIONALE: Coal tars are a mixture of organic and inorganic compounds that were
      produced as a by-product from the manufactured gas and coke making industries.
      The composition of the tar produced varies depending on many factors; these
      include the temperature of production and the type of retort used. As different
      production processes produce different tars, a comprehensive database of the
      compounds present within coal tars from different production processes is a
      valuable resource. Such a database would help to understand how their chemical
      properties differ and what hazards the compounds present within these tars might
      pose. This study focuses on the aliphatic and aromatic compounds present in a
      database of 16 different tars from five different production processes. METHODS:
      Samples of coal tar were extracted using accelerated solvent extraction (ASE) and
      derivatised post-extraction using N,O-bis(trimethylsilyl)trifluoroacetamide
      (BSTFA) with 1% trimethylchlorosilane (TMCS). The derivatised samples were
      analysed using two-dimensional gas chromatography combined with time-of-flight
      mass spectrometry (GCxGC/TOFMS). RESULTS: A total of 198 individual aliphatic and
      951 individual aromatic compounds were detected within 16 tar samples produced by
      five different production processes. The polycyclic aromatic hydrocarbon (PAH)
      content of coal tars varies greatly depending on the production process used to
      obtain the tars and this is clearly demonstrated within the results. The
      aliphatic composition of the tars provided an important piece of analytical
      information that would have otherwise been missed with the detection of
      petrogenic compounds such as alkyl cyclohexanes. CONCLUSIONS: The aromatic
      compositions of the tar samples varied greatly between the different production
      processes investigated and useful analytical information was obtained about the
      individual production process groups. Alkyl cyclohexanes were detected in all
      samples from sites known to operate Carbureted Water Gas plants and not detected
      in those that did not. This suggests that petrogenic material may be expected at
      many UK gaswork sites.

PMID- 28494123
TI  - Ecological momentary interventions for depression and anxiety.
AB  - Ecological momentary interventions (EMIs) are becoming more popular and more
      powerful resources for the treatment and prevention of depression and anxiety due
      to advances in technological capacity and analytic sophistication. Previous work
      has demonstrated that EMIs can be effective at reducing symptoms of depression
      and anxiety as well as related outcomes of stress and at increasing positive
      psychological functioning. In this review, we highlight the differences between
      EMIs and other forms of treatment due to the nature of EMIs to be deeply
      integrated into the fabric of people's day-to-day lives. EMIs require unique
      considerations in their design, deployment, and evaluation. Furthermore, given
      that EMIs have been advanced by changes in technologies and that the use of
      behavioral intervention technologies for mental health has been increasing, we
      discuss how technologies and analytics might usher in a new era of EMIs. Future
      EMIs might reduce user burden and increase intervention personalization and
      sophistication by leveraging digital sensors and advances in natural language
      processing and machine learning. Thus, although current EMIs are effective, the
      EMIs of the future might be more engaging, responsive, and adaptable to different
      people and different contexts.

PMID- 28494124
TI  - Professor Crispian Scully CBE, DSc, DChD, DMed (HC), Dhc (multi), MD, PhD, PhD
      (HC), FMedSci, MDS, MRCS, BSc, FDSRCS, FDSRCPS, FFDRCSI, FDSRCSEd FRCPath, FHEA
      (1945-2017).

PMID- 28494125
TI  - Harassment and Mental Distress Among Adolescent Female Students by Sexual
      Identity and BMI or Perceived Weight Status.
AB  - OBJECTIVE: Sexual minority girls (lesbian/bisexual) and girls with
      overweight/obesity experience high rates of discrimination and mental distress.
      This study explored whether BMI or perceived weight status might compound sexual
      minority girls' risk for harassment and mental distress. METHODS: Data on female
      students from the national 2015 Youth Risk Behavior Survey (n = 7,006) were
      analyzed. Logistic regression was used to examine differences in bullying,
      harassment, and mental distress across sexual identity/BMI groups:
      heterosexual/normal-weight, heterosexual/overweight, sexual minority/normal
      weight, and sexual minority/overweight. Procedures were repeated with four
      analogous groups created from sexual identity and perceived weight. RESULTS:
      Across sexual identity/BMI groups, being overweight increased heterosexual
      females' odds of being bullied or experiencing suicidal thoughts and behaviors.
      Regardless of weight status, sexual minority females had greater odds for each
      outcome than heterosexual females. Sexual minority females who perceived
      themselves as overweight had greater odds of suicidality than all other sexual
      minority/perceived weight groups. CONCLUSIONS: Double jeopardy may exist for
      sexual minority female students who perceive themselves as overweight.
      Professional development with school staff on how to create a positive climate
      for sexual minorities and those with overweight/obesity and addressing positive
      identity and body image within school-based suicide prevention efforts may be
      important to the well-being of adolescent girls.

PMID- 28494127
TI  - Does iron reduction control the release of dissolved organic carbon and phosphate
      at catchment scales? Need for a joint research effort.
AB  - Increasing concentrations of dissolved iron and DOC are likely linked to
      decreasing nitrogen depositon.

PMID- 28494128
TI  - Alcohol consumption, cigarette smoking and incidence of aortic valve stenosis.
AB  - BACKGROUND: Alcohol consumption and cigarette smoking are modifiable lifestyle
      factors with important impact on public health. It is unclear whether these
      factors influence the risk of aortic valve stenosis (AVS). OBJECTIVE: To
      investigate the associations of alcohol consumption and smoking, including
      smoking intensity and time since cessation, with AVS incidence in two prospective
      cohorts. METHODS: This analysis was based on data from the Swedish Mammography
      Cohort and the Cohort of Swedish Men, comprising 69 365 adults without
      cardiovascular disease at baseline. Participants were followed for AVS incidence
      and death by linkage to the Swedish National Patient and Causes of Death
      Registers. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated
      by Cox proportional hazards regression. RESULTS: Over a mean follow-up of 15.3
      years, 1249 cases of AVS (494 in women and 755 in men) were recorded. Compared
      with never drinkers of alcohol (lifelong abstainers), the risk of AVS was
      significantly lower in current light drinkers (1-6 drinks per week [1 drink = 12
      g alcohol]; multivariable HR 0.82; 95% CI: 0.68-0.99). The risk of AVS increased
      with increasing smoking intensity. Compared with never smokers, the HR was 1.46
      (95% CI: 1.16-1.85) in current smokers of >=30 pack-years. Former smokers who had
      quit smoking 10 or more years previously had similar risk for AVS as never
      smokers. CONCLUSIONS: This study suggests that current light alcohol consumption
      is associated with a lower risk of AVS, and indicates that the association
      between smoking and AVS risk is reversible.

PMID- 28494126
TI  - Real-life glycemic control in patients with type 2 diabetes treated with insulin
      therapy: A prospective, longitudinal cohort study (Diabetes Distress and Care
      Registry at Tenri [DDCRT 9]).
AB  - AIMS/INTRODUCTION: We investigated the association between four insulin regimens,
      and increase in glycated hemoglobin (HbA1c) and insulin dose in a real-life
      clinical setting because there are no data about them among insulin regimens.
      MATERIALS AND METHODS: Participants included 757 patients with type 2 diabetes
      having been treated with insulin therapy for more than 1 year. The four insulin
      regimens were regimen 1 (long-acting insulin, once daily), regimen 2 (biphasic
      insulin, twice daily), regimen 3 (biphasic insulin, three times daily) and
      regimen 4 (basal-bolus therapy). Main outcomes were increases in HbA1c levels
      >0.5% and increases in daily insulin units after 1 year. We carried out
      multivariable analyses to examine differences in glycemic control and insulin
      dose with adjustment for possible confounders. RESULTS: Mean HbA1c level and
      duration of insulin therapy were 7.8% and 11.3 years, respectively. HbA1c levels
      increased by >0.5% at follow up in 22.8, 24.9, 20.7, and 29.3% of participants
      using regimen 1, 2, 3 and 4, respectively, with no significant differences
      between groups. Daily insulin doses increased in 62.3, 68.8, 65.3 and 38.6% of
      patients, respectively (P < 0.001). Multivariable regression analysis showed that
      patients who received regimen 4 had significantly lower odds of requiring future
      insulin dose increases than those who had received regimen 2 (adjusted odds ratio
      0.24, 95% confidence interval 0.14-0.41; P < 0.001). CONCLUSIONS: Many patients
      receiving insulin therapy showed increases in HbA1c levels and insulin doses 1
      year later. The smallest increase in insulin dose was observed in the basal-bolus
      therapy group compared with other regimens.

PMID- 28494129
TI  - When trust is threatened: Qualitative study of parents' perspectives on
      problematic clinical relationships in child cancer care.
AB  - OBJECTIVE: We explored parents' accounts of the parent-clinician relationship in
      childhood cancer to understand how parents who perceive threats to the
      relationship can be supported. METHODS: Multicentre longitudinal qualitative
      study, with 67 UK parents of children (aged 1-12 years) receiving treatment for
      acute lymphoblastic leukaemia. Analyses drew on the wider sample but focussed on
      50 semistructured interviews with 20 parents and were informed by constant
      comparison. RESULTS: All 20 parents described problems with clinical care such as
      inadequate information or mistakes by staff but varied in how much the problems
      threatened their sense of relationship with clinicians. Some parents saw the
      problems as having no relevance to the parent-clinician relationship. Others saw
      the problems as threats to the clinical relationship but worked to "contain" the
      threat in ways that preserved a trusting relationship with at least one senior
      clinician. Parents' containment work protected the security they needed from the
      parent-clinician relationship, but containment was a tenuous process for some. A
      few parents were unable to contain the problems at all; lacking trust in
      clinicians, these parents suffered considerably. CONCLUSIONS: Given the
      complexity of childhood cancer care, problems with clinical care are inevitable.
      By engaging in containment work, parents met their needs to feel secure in the
      face of these problems, but the extent to which parents should have to do this
      work is debatable. Parents could benefit from support to seek help when problems
      arise which threaten their trust in clinicians. Attachment theory can guide
      clinicians in giving this support.

PMID- 28494130
TI  - Visualization of stereoscopic anatomic models of the paranasal sinuses and
      cervical vertebrae from the surgical and procedural perspective.
AB  - Recent improvements in three-dimensional (3D) virtual modeling software allows
      anatomists to generate high-resolution, visually appealing, colored, anatomical
      3D models from computed tomography (CT) images. In this study, high-resolution CT
      images of a cadaver were used to develop clinically relevant anatomic models
      including facial skull, nasal cavity, septum, turbinates, paranasal sinuses,
      optic nerve, pituitary gland, carotid artery, cervical vertebrae, atlanto-axial
      joint, cervical spinal cord, cervical nerve root, and vertebral artery that can
      be used to teach clinical trainees (students, residents, and fellows) approaches
      for trans-sphenoidal pituitary surgery and cervical spine injection procedure.
      Volume, surface rendering and a new rendering technique, semi-auto-combined, were
      applied in the study. These models enable visualization, manipulation, and
      interaction on a computer and can be presented in a stereoscopic 3D virtual
      environment, which makes users feel as if they are inside the model. Anat Sci
      Educ 10: 598-606. (c) 2017 American Association of Anatomists.

PMID- 28494132
TI  - Issue Information - ToC.

PMID- 28494131
TI  - Neuropsychological functioning in college students who misuse prescription
      stimulants.
AB  - BACKGROUND AND OBJECTIVES: Relatively little is known about the
      neuropsychological profiles of college students who misuse prescription stimulant
      medications. METHODS: Data presented are from college students aged 18-28 years
      who misused prescription stimulants prescribed for attention
      deficit/hyperactivity disorder and controls (no prescription stimulant misuse).
      Students were assessed neuropsychologically using the self-report Behavioral
      Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated
      Neuropsychological Test and Battery (CANTAB), and other tests of cognitive
      functioning. The analyses included 198 controls (age 20.7 +/- 2.6 years) and 100
      prescription stimulant misusers (age 20.7 +/- 1.7 years). RESULTS: On the BRIEF
      A, misusers were more likely than controls to endorse greater dysfunction on 8 of
      12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and
      Plan/Organize, when adjusting for race and sex (all p's < .05). Similarly, when
      dichotomizing the BRIEF-A as abnormal (T score >= 65), misusers had more
      abnormalities on five of nine subscales, as well as all major indices (p's <
      .05). Misusers also performed worse on several subtests of the CANTAB and
      standardized cognitive battery (p's < .05). A proxy of prescription stimulant
      misuse frequency was positively correlated with greater executive dysfunction on
      the BRIEF-A. DISCUSSION AND CONCLUSIONS: These data demonstrate elevated risk for
      neuropsychological dysfunction among students who misuse prescription stimulants
      compared to non-misusing peers. The presence of ADHD contributed significantly to
      these cognitive findings. Students who misuse prescription stimulants should be
      screened for neuropsychological dysfunction. SCIENTIFIC SIGNIFICANCE: These data
      may better elucidate the neuropsychological profile of college-aged prescription
      stimulant misusers. (Am J Addict 2017;26:379-387).

PMID- 28494134
TI  - Issue Information - Editorial Board.

PMID- 28494133
TI  - Interaction between ADH1B*3 and alcohol-facilitating social environments in
      alcohol behaviors among college students of african descent.
AB  - BACKGROUND AND OBJECTIVES: Although alcohol-facilitating social environmental
      factors, such as alcohol offers and high perceived peer drinking norms, have been
      extensively studied as determinants of college drinking, their role among college
      students of African descent remains understudied. Furthermore, gene-environment
      interaction research suggests that the effects of alcohol-facilitating
      environments may differ as a function of genetic factors. Specifically, the
      alcohol dehydrogenase gene's ADH1B*3 allele, found almost exclusively in persons
      of African descent, may modulate the association of risky social environments
      with alcohol behaviors. The current study examined whether the ADH1B*3 allele
      attenuated the relationship between alcohol-facilitating environments (ie,
      alcohol offers and perceived peer drinking norms) and alcohol behaviors. METHOD:
      Participants were 241 undergraduate students who self-identified as being of
      African descent (mean age = 20 years [SD = 4.11]; 66% female). RESULTS:
      Significant interaction effects of ADH1B*3 with alcohol offers were found on
      alcohol use frequency (incidence rate ratio [IRR] = 1.14) and on drinking
      consequences (IRR = 1.21). ADH1B*3 also interacted with perceived peer norms on
      drinking consequences (IRR = 1.41). Carriers of the ADH1B*3 allele drank less
      frequently and experienced fewer negative consequences than non-carriers when
      exposed to lower levels of alcohol offers and perceived peer drinking. In
      contrast, in high alcohol-facilitating environments, no protective genetic effect
      was observed. DISCUSSION AND CONCLUSION: This study demonstrates that ADH1B*3 may
      protect college students of African descent against alcohol outcomes, although
      only in low alcohol-facilitating environments. SCIENTIFIC SIGNIFICANCE: Findings
      add to the growing body of knowledge regarding genetic and social determinants of
      alcohol behaviors among college students of African descent. (Am J Addict
      2017;26:349-356).

PMID- 28494135
TI  - Prospective association between body mass index at midlife and healthy aging
      among French adults.
AB  - OBJECTIVE: To assess the association between midlife body mass index (BMI) and
      healthy aging (HA) in the French SU.VI.MAX cohort. METHODS: HA was assessed in
      2007 to 2009 among 2,733 individuals, aged 45 to 60 years and free of diabetes,
      cardiovascular disease and cancer at baseline (1994-1995). HA was defined as not
      developing any major chronic disease, good physical and cognitive functioning, no
      limitations in instrumental activities of daily living, no depressive symptoms,
      no health-related limitations in social life, good overall self-perceived health,
      and no function-limiting pain. Associations between anthropometric indicators
      (measured in 1995-1996) and HA were assessed using robust-error-variance Poisson
      regression. RESULTS: After adjustment for potential confounders, BMI (continuous)
      was negatively associated with HA: relative risk (RR) = 0.97 (95% confidence
      interval = 0.96-0.99). Moreover, the detrimental role of obesity (RRobesity vs.
      normal weight  = 0.67 [0.51-0.88]) was substantially stronger than that of
      overweight (RRoverweight vs. normal weight  = 0.91 [0.81-1.01]). Furthermore,
      while metabolically healthy individuals with overweight had a similar HA
      probability as metabolically healthy individuals with normal weight,
      metabolically unhealthy overweight individuals had a substantially lowered HA
      probability. CONCLUSIONS: This study provides novel evidence that an elevated BMI
      at midlife may jeopardize the preservation of health during aging. Our results
      also highlight the importance of maintaining a healthy metabolic profile during
      midlife.

PMID- 28494136
TI  - Effects of an abbreviated obesity intervention supported by mobile technology:
      The ENGAGED randomized clinical trial.
AB  - OBJECTIVE: To determine the effects on weight loss of three abbreviated
      behavioral weight loss interventions with and without coaching and mobile
      technology. METHODS: A randomized controlled efficacy study of three 6-month
      weight loss treatments was conducted in 96 adults with obesity: 1) self-guided
      (SELF), 2) standard (STND), or 3) technology-supported (TECH). STND and TECH
      received eight in-person group treatment sessions. SELF and STND used paper
      diaries to self-monitor diet, activity, and weight; TECH used a smartphone
      application with social networking features and wireless accelerometer. RESULTS:
      Weight loss was greater for TECH and STND than SELF at 6 months (-5.7 kg [95%
      confidence interval: -7.2 to -4.1] vs. -2.7 kg [95% confidence interval: -5.1 to 
      0.3], P < 0.05) but not 12 months. TECH and STND did not differ except that more
      STND (59%) than TECH (34%) achieved >= 5% weight loss at 6 months (P < 0.05).
      Self-monitoring adherence was greater in TECH than STND (P < 0.001), greater in
      both interventions than SELF (P < 0.001), and covaried with weight loss (r(84) =
      0.36-0.51, P < 0.001). CONCLUSIONS: Abbreviated behavioral counseling can produce
      clinically meaningful weight loss regardless of whether self-monitoring is
      performed on paper or smartphone, but long-term superiority over standard of care
      self-guided treatment is challenging to maintain.

PMID- 28494137
TI  - Acute radiology rarely confirms sinus disease in suspected recurrent acute
      rhinosinusitis.
AB  - BACKGROUND: Episodic or recurrent sinonasal symptoms are often suspected as
      "sinus" in origin. With normal sinus radiology between events, the diagnosis of
      recurrent acute rhinosinusitis (RecARS) is made. However, other conditions can
      produce episodic symptoms. In this study we analyze acutely performed computed
      tomography (CT) in a population with suspected or self-diagnosed "sinus" disease.
      METHODS: Patients referred to a tertiary clinic for suspected RecARS were
      assessed. Sinus changes were defined by CT (initial assessment) and during the
      acute event, by a semiurgent CT performed during the symptomatic episode. Mucosal
      thickening, ostiomeatal compromise, and severe septal deformity were recorded.
      Symptom profile was assessed during both time-points with the 22-item Sino-Nasal
      Outcome Test (SNOT-22). RESULTS: Forty-eight patients (49.5 +/- 14.7 years of
      age, 70.8% female) were assessed. At presentation, 75% were resolute in a
      diagnosis of "sinus." Baseline Lund-Mackay scores were <6 (median 0
      [interquartile range 1]). Ostiomeatal compromise was 6.8% left and 4.5% right at
      baseline. Of the patients who returned for acute CT (n = 27), SNOT-22 and
      subdomains were similar to baseline. Septal deviation was similar (13.6% vs
      15.3%). Acutely, ostiomeatal compromise was 0% left and 7.4% right (n = 2). Of
      these 2 patients with ostiomeatal compromise, 1 was diagnosed with RecARS (4%)
      and the other with triptan-responsive migraine, with incidental sinus changes.
      Final diagnosis was rhinitis (47%), headache/migraine (37%), and facial pain
      otherwise undefined (12.5%). CONCLUSION: Patients with a history of "recurrent
      acute sinusitis" and normal CT scans between episodes rarely have abnormal CT
      findings during acute exacerbations of symptoms. Antibiotics and surgical
      intervention are often inappropriate in this population.

PMID- 28494138
TI  - Rational Design and Synthesis of 1-(Arylideneamino)-4-aryl-1H-imidazole-2-amine
      Derivatives as Antiplatelet Agents.
AB  - Based on previous studies indicating the pharmacophoric role of a hydrazone group
      and azole rings for antiplatelet aggregation activity, a few series of compounds
      with both hydrazone and an azole (imidazole) ring in their structures were
      synthesized, and their platelet aggregation inhibitory effects were evaluated.
      Two of these 1-(arylideneamino)-4-aryl-1H-imidazole-2-amine derivatives,
      compounds 4 a [(E)-1-(benzylideneamino)-4-phenyl-1H-imidazol-2-amine] and 4 p
      [(E)-4-phenyl-1-((thiophen-2-ylmethylene)amino)-1H-imidazol-2-amine], exhibited
      IC50 values similar to that of acetylsalicylic acid against collagen as a
      platelet aggregation inducer. Structural comparison of the synthesized compounds
      revealed that those with a para-substituted phenyl ring on the imidazole were
      among the most active compounds against platelet aggregation induced by
      arachidonic acid (AA), and the presence of a thiophene ring in these compounds
      maximized their antiplatelet activity.

PMID- 28494139
TI  - Corrigendum to Hsueh (2016), "Neurofeedback training of EEG alpha rhythm enhances
      episodic and working memory."

PMID- 28494140
TI  - Identification of alpha7 Nicotinic Acetylcholine Receptor Silent Agonists Based
      on the Spirocyclic Quinuclidine-Delta2 -Isoxazoline Scaffold: Synthesis and
      Electrophysiological Evaluation.
AB  - Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'
      bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic
      ligands as a suitable model compound for the design of new silent agonists of
      alpha7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little
      or no channel activation but can induce the alpha7 desensitized Ds state, which
      is sensitive to a type II positive allosteric modulator, such as PNU-120596.
      Introduction of meta substituents into the benzyloxy moiety of 11 led to two sets
      of tertiary amines and quaternary ammonium salts based on the spirocyclic
      quinuclidinyl-Delta2 -isoxazoline scaffold. Electrophysiological assays performed
      on Xenopus laevis oocytes expressing human alpha7 nAChRs highlighted four
      compounds that are endowed with a significant silent-agonism profile. Structure
      activity relationships of this group of analogues provided evidence of the
      crucial role of the positive charge at the quaternary quinuclidine nitrogen atom.
      Moreover, the present study indicates that meta substituents, in particular
      halogens, on the benzyloxy substructure direct specific interactions that
      stabilize a desensitized conformational state of the receptor and induce silent
      activity.

PMID- 28494141
TI  - Metformin induces osteoblastic differentiation of human induced pluripotent stem
      cell-derived mesenchymal stem cells.
AB  - Metformin, a first-line antidiabetic drug used by millions of patients, has been
      shown to have potential osteogenic properties. The present study was performed to
      test the hypothesis that clinically relevant doses of metformin promote the
      osteogenic differentiation and mineralization of induced pluripotent stem cell
      derived mesenchymal stem cells (iPSC-MSCs). iPSC-MSCs were treated with metformin
      (10 MUm) to assess cell viability, osteogenic differentiation, mineralization and
      activation of the LKB1/AMP-activated protein kinase (AMPK) signalling pathway, a
      surrogate marker of metformin action. To determine its potential application in
      MSC-based bone and periodontal tissue engineering, iPSC-MSCs were also treated
      with metformin when seeded on to calcium phosphate cement (CPC) scaffolds.
      Immunoblotting and cellular uptake assays showed that iPSC-MSCs express
      functional organic cation transporter-1 (OCT-1), a transmembrane protein that
      mediates the intracellular uptake of metformin. Although metformin treatment did
      not impair iPSC-MSC viability, it significantly stimulated alkaline phosphatase
      activity, enhanced mineralized nodule formation and increased expression of
      osteogenic markers, including Runt-related transcription factor 2 (RUNX2) and
      osterix. Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly
      reversed metformin-induced AMPK activation, RUNX2 expression and nuclear
      localization. Moreover, metformin substantially increased mineralized nodule
      formation of iPSC-MSC seeded on CPC scaffolds. Collectively, functional OCT
      expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in
      part mediated by the LKB1/AMPK pathway. Considering the widespread use of
      metformin in diabetics, this work may lead to novel tissue-engineering platforms
      where autogenous OCT-expressing iPSC-MSCs might be used to enhance bone and
      periodontal regeneration in diabetic patients prescribed with daily doses of
      metformin.

PMID- 28494142
TI  - Blood pressure circadian rhythms and adverse outcomes in type 2 diabetes patients
      diagnosed with orthostatic hypotension.
AB  - AIMS/INTRODUCTION: Patients with diabetes frequently develop orthostatic
      hypotension (OH). The present study was designed to examine the relationship of
      blood pressure (BP) circadian rhythms and outcomes in diabetes with OH. MATERIALS
      AND METHODS: In the present study, 173 inpatients with type 2 diabetes were
      enrolled. Patients were divided into an OH group and a non-OH group according to
      the BP changes detected in the supine and standing position. Then, 24-h
      ambulatory BP was monitored. Patients were followed up for an average of 45 +/-
      10 months post-discharge. Outcomes - death and major adverse cardiac and
      cerebrovascular events, including heart failure, myocardial infarction and stroke
      - were recorded. RESULTS: There were 61 patients (35.26%) in the OH group and 112
      patients (64.74%) in the non-OH group. In the OH group, the night-time systolic
      BP and night-time diastolic BP were higher, the blood BP rhythms were
      predominantly of the riser type (67.21%). OH was as an independent marker of
      riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval
      2.579-7.966). In the OH group, the incidence rates of mortality, and major
      adverse cardiac and cerebrovascular events were increased significantly compared
      with those in the non-OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P <
      0.01). CONCLUSIONS: In patients who had type 2 diabetes diagnosed with OH, the BP
      circadian rhythm usually showed riser patterns, and they had increased rates of
      mortality, and major adverse cardiac and cerebrovascular events.

PMID- 28494144
TI  - Thermo-optical Characterization of Photothermal Optical Phase Shift Detection in
      Extended-Nano Channels and UV Detection of Biomolecules.
AB  - The expansion of microfluidics research to nanofluidics requires absolutely
      sensitive and universal detection methods. Photothermal detection, which utilizes
      optical absorption and nonradiative relaxation, is promising for the sensitive
      detection of nonlabeled biomolecules in nanofluidic channels. We have previously
      developed a photothermal optical phase shift (POPS) detection method to detect
      nonfluorescent molecules sensitively, while a rapid decrease of the sensitivity
      in nanochannels and the introduction of an ultraviolet (UV) excitation system
      were issues to be addressed. In the present study, our primary aim is to
      characterize the POPS signal in terms of the thermo-optical properties and
      quantitatively evaluate the causes for the decrease in sensitivity. The UV
      excitation system is then introduced into the POPS detector to realize the
      sensitive detection of nonlabeled biomolecules. The UV-POPS detection system is
      designed and constructed from scratch based on a symmetric microscope. The
      results of simulations and experiments reveal that the sensitivity decreases due
      to a reduction of the detection volume, dissipation of the heat, and cancellation
      of the changes in the refractive indices. Finally, determination of the
      concentration of a nonlabeled protein (bovine serum albumin) is performed in a
      very thin 900 nm deep nanochannel. As a result, the limit of detection (LOD) is
      2.3 MUM (600 molecules in the 440 attoliter detection volume), which is as low as
      that previously obtained for our visible POPS detector. UV-POPS detection is thus
      expected be a powerful technique for the study of biomolecules, including DNAs
      and proteins confined in nanofluidic channels.

PMID- 28494143
TI  - Normal meal tolerance test is preferable to the glucagon stimulation test in
      patients with type 2 diabetes that are not in a hyperglycemic state: Comparison
      with the change of C-peptide immunoreactivity.
AB  - AIMS/INTRODUCTION: The aim of the present study was to evaluate the properties of
      the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in
      patients with type 2 diabetes. MATERIALS AND METHODS: We enrolled 142 patients
      with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT
      using a calorie-controlled meal based on an intake of 30 kcal/kg ideal
      bodyweight/day. We calculated the change in C-peptide immunoreactivity (DeltaCPR)
      by subtracting fasting CPR from the CPR 6 min after the 1-mg glucagon injection
      (GST) or 120 min after the meal (NMTT). RESULTS: Mean DeltaCPR for the GST was
      2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater
      DeltaCPR in the NMTT than the GST, and the mean DeltaCPR was significantly
      greater in the NMTT than the GST (P < 0.05). To exclude any influence of
      antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents,
      and found the mean DeltaCPR was significantly greater in the NMTT than the GST
      (GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose
      toxicity, we carried out receiver operating characteristic analyses with fasting
      plasma glucose and glycated hemoglobin. The optimal cut-off levels predicting GST
      DeltaCPR to be larger than NMTT DeltaCPR were fasting plasma glucose 147 mg/dL
      and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64,
      specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity
      0.56, specificity 0.71, area under the curve 0.66). CONCLUSIONS: The NMTT is a
      reliable insulin secretion test in patients with type 2 diabetes, except for
      those in a hyperglycemic state.

PMID- 28494145
TI  - Direct Plasmon-Accelerated Electrochemical Reaction on Gold Nanoparticles.
AB  - Direct photocatalysis making use of plasmonic metals has attracted significant
      attention due to the light-harnessing capabilities of these materials associated
      with localized surface plasmon resonance (LSPR) features. Thus far, most reported
      work has been limited to plasmon-induced chemical transformations. Herein, we
      demonstrate that electrochemical reactions can also be accelerated by plasmonic
      nanoparticles upon LSPR excitation. Using glucose electrocatalysis as a model
      reaction system, the direct plasmon-accelerated electrochemical reaction (PAER)
      on gold nanoparticles is observed. The wavelength- and solution-pH-dependent
      electrochemical oxidation rate and the dark-field scattering spectroscopy results
      confirm that the hot charge carriers generated during plasmon decay are
      responsible for the enhanced electrocatalysis performance. Based on the proposed
      PAER mechanism, a plasmon-improved glucose electrochemical sensor is constructed,
      demonstrating the enhanced performance of the non-enzyme sensor upon LSPR
      excitation. This plasmon-accelerated electrochemistry promises potential
      applications in (bio)electrochemical energy conversion, electroanalysis, and
      electrochemical devices.

PMID- 28494146
TI  - Redox-Induced Gating of the Exchange Interactions in a Single Organic Diradical.
AB  - Embedding a magnetic electroactive molecule in a three-terminal junction allows
      for the fast and local electric field control of magnetic properties desirable in
      spintronic devices and quantum gates. Here, we provide an example of this control
      through the reversible and stable charging of a single all-organic neutral
      diradical molecule. By means of inelastic electron tunnel spectroscopy we show
      that the added electron occupies a molecular orbital distinct from those
      containing the two radical electrons, forming a spin system with three
      antiferromagnetically coupled spins. Changing the redox state of the molecule
      therefore switches on and off a parallel exchange path between the two radical
      spins through the added electron. This electrically controlled gating of the
      intramolecular magnetic interactions constitutes an essential ingredient of a
      single-molecule [Formula: see text] quantum gate.

PMID- 28494147
TI  - Structural Insight into the Stabilizing Effect of O-Glycosylation.
AB  - Protein glycosylation has been shown to have a variety of site-specific and
      glycan-specific effects, but so far, the molecular logic that leads to such
      observations has been elusive. Understanding the structural changes that occur
      and being able to correlate those with the physical properties of the
      glycopeptide are valuable steps toward being able to predict how specific
      glycosylation patterns will affect the stability of glycoproteins. By
      systematically comparing the structural features of the O-glycosylated
      carbohydrate-binding module of a Trichoderma reesei-derived Family 7
      cellobiohydrolase, we were able to develop a better understanding of the
      influence of O-glycan structure on the molecule's physical stability. Our results
      indicate that the previously observed stabilizing effects of O-glycans come from
      the introduction of new bonding interactions to the structure and increased
      rigidity, while the decreased stability seemed to result from the impaired
      interactions and increased conformational flexibility. This type of knowledge
      provides a powerful and potentially general mechanism for improving the stability
      of proteins through glycoengineering.

PMID- 28494148
TI  - Raman Spectroscopy of Lattice-Matched Graphene on Strongly Interacting Metal
      Surfaces.
AB  - Regardless of the widely accepted opinion that there is no Raman signal from
      single-layer graphene when it is strongly bonded to a metal surface, we present
      Raman spectra of a graphene monolayer on Ni(111) and Co(0001) substrates. The
      high binding energy of carbon to these surfaces allows formation of lattice
      matched (1 * 1) structures where graphene is significantly stretched. This is
      reflected in a record-breaking shift of the Raman G band by more than 100 cm-1
      relative to the case of freestanding graphene. Using electron diffraction and
      photoemission spectroscopy, we explore the aforementioned systems together with
      polycrystalline graphene on Co and analyze possible intercalation of oxygen at
      ambient conditions. The results obtained are fully supported by Raman
      spectroscopy. Performing a theoretical investigation of the phonon dispersions of
      freestanding graphene and stretched graphene on the strongly interacting Co
      surface, we explain the main features of the Raman spectra. Our results create a
      reliable platform for application of Raman spectroscopy in diagnostics of
      chemisorbed graphene and related materials.

PMID- 28494149
TI  - Comparison of Three Antihapten VHH Selection Strategies for the Development of
      Highly Sensitive Immunoassays for Microcystins.
AB  - Owing to their reproducibility, stability, and cost-effective production, the
      recombinant variable domains of heavy-chain-only antibodies (VHHs) are becoming a
      salient option as immunoassay reagents. Recently, there have been several reports
      describing their application to the detection of small molecules (haptens).
      However, lacking the heavy-light chain interface of conventional antibodies, VHHs
      are not particularly apt to bind small analytes and failures are not uncommon.
      Here we describe the construction of a VHH phage display library against the
      cyanobacterial hepatotoxin microcystin LR and its selection using competitive
      panning and two novel panning strategies. The outcome of each strategy was
      evaluated by a large-scale screening using in vivo biotinylated nanobodies. The
      three methods selected for different nonoverlapping subsets of VHHs, allowing one
      to optimize the immunodetection of the toxin. The best results were obtained by
      promoting the isolation of VHHs with the slowest koff (off-rate selection). Among
      these, the biotinylated nanobody A2.3 performed in ELISA with excellent recovery
      and high sensitivity, IC50 = 0.28 MUg/L, with a limit of detection that is well
      below the most rigorous guidelines for the toxin. While it may be case-specific,
      these results highlight the importance of exploring different panning strategies
      to optimize the selection of antihapten nanobodies.

PMID- 28494150
TI  - Nondestructive Redox Quantification Reveals Glassmaking of Rare French Gothic
      Stained Glasses.
AB  - The sophisticated colors of medieval glasses arise from their transition metal
      (TM) impurities and capture information about ancient glassmaking techniques.
      Beyond the glass chemical composition, the TM redox is also a key factor in the
      glass color, but its quantification without any sampling is a challenge. We
      report a combination of nondestructive and noninvasive quantitative analyses of
      the chemical composition by particle-induced X-ray emission-particle-induced
      gamma-ray emission mappings and of the color and TM element speciation by optical
      absorption spectroscopy performed on a red-blue-purple striped glass from the
      stained glass windows of the Sainte-Chapelle in Paris, France, during its
      restoration. These particular glass pieces must have been produced as a single
      shot, which guarantees that the chemical variations reflect the recipe in use in
      a specific medieval workshop. The quantitative elemental mappings demonstrate
      that the colored glass parts are derived from the same base glass, to which TMs
      were deliberately added. Optical absorption spectra reveal the origin of the
      colors: blue from CoII, red from copper nanoparticles, and purple from MnIII.
      Furthermore, the derivation of the quantitative redox state of each TM in each
      color shows that the contents of Fe, Cu, and Mn were adjusted to ensure a
      reducing glass matrix in the red stripe or a metastable overoxidized glass in the
      purple stripe. We infer that the agility of the medieval glassmaker allowed him
      to master the redox kinetics in the glass by rapid shaping and cooling to obtain
      a snapshot of the thermodynamically unstable glass colors.

PMID- 28494151
TI  - Design of HIV Coreceptor Derived Peptides That Inhibit Viral Entry at
      Submicromolar Concentrations.
AB  - HIV/AIDS continues to pose an enormous burden on global health. Current HIV
      therapeutics include inhibitors that target the enzymes HIV protease, reverse
      transcriptase, and integrase, along with viral entry inhibitors that block the
      initial steps of HIV infection by preventing membrane fusion or virus-coreceptor
      interactions. With regard to the latter, peptides derived from the HIV coreceptor
      CCR5 were previously shown to modestly inhibit entry of CCR5-tropic HIV strains,
      with a peptide containing residues 178-191 of the second extracellular loop
      (peptide 2C) showing the strongest inhibition. Here we use an iterative approach
      of amino acid scanning at positions shown to be important for binding the HIV
      envelope, and recombining favorable substitutions to greatly improve the potency
      of 2C. The most potent candidate peptides gain neutralization breadth and inhibit
      CXCR4 and CXCR4/CCR5-using viruses, rather than CCR5-tropic strains only. We
      found that gains in potency in the absence of toxicity were highly dependent on
      amino acid position and residue type. Using virion capture assays we show that 2C
      and the new peptides inhibit capture of CD4-bound HIV-1 particles by antibodies
      whose epitopes are located in or around variable loop 3 (V3) on gp120. Analysis
      of antibody binding data indicates that interactions between CCR5 ECL2-derived
      peptides and gp120 are localized around the base and stem of V3 more than the
      tip. In the absence of a high-resolution structure of gp120 bound to coreceptor
      CCR5, these findings may facilitate structural studies of CCR5 surrogates, design
      of peptidomimetics with increased potency, or use as functional probes for
      further study of HIV-1 gp120-coreceptor interactions.

PMID- 28494152
TI  - Low-Temperature Synthesis of Carbon-Rich Nanoparticles with a Clickable Surface
      for Functionalization.
AB  - Carbon nanoparticles (CNPs) are promising materials for optoelectronic and
      biomedical applications thanks to their optical properties, low production cost,
      and superior biocompatibility compared to traditional semiconductor quantum dots.
      The countless synthetic methods reported allow a library of diverse CNP
      structures and optical properties, guiding their subsequent applications.
      However, the current drawbacks lie mainly within these synthetic processes, as
      many of them require harsh conditions preventing control over morphology and
      often generating chemically inert nanoparticles. Thus, more advances on low
      temperature and controllable synthetic processes are desirable. In this study, we
      suggest a new strategy to synthesize CNPs with tunable size, while avoiding the
      use of harsh conditions and allowing easy surface functionalization. The
      metastable state of polyyne-containing materials appoints them as ideal
      precursors for low-temperature preparation of carbon-rich structures. Our
      approach is to synthesize octatetrayne-containing particles prompt to spontaneous
      reaction, including topochemical polymerization, followed by aromatization, to
      avoid harsh carbonization steps. For the particle synthesis, the well-known
      dispersion polymerization process has been adapted for homocoupling of terminal
      butadiynes, generating the octatetrayne-containing particles. The method was
      proven reproducible, scalable, and versatile, as the particles' size can be
      modulated between 50 and 170 nm. Surface functionalization via thiol-yne click
      chemistry was completed with a pyrene-modified thiol ligand to provide the CNPs
      with photoactive properties in the visible range. The functionalized particles
      exhibit fluorescence at 470 nm arising from excimer formation.

PMID- 28494153
TI  - Polyaniline and Perfluorosulfonic Acid Co-Stabilized Metal Catalysts for Oxygen
      Reduction Reaction.
AB  - A proton (perfluorosulfonic acid, PFSA) and electron (polyaniline, PANI)
      conductor polymer costabilized Pt catalyst (Pt-PFSA/C@PANI) is synthesized to
      improve the long-term stability of polymer electrolyte membrane fuel cells
      (PEMFCs). The prepared catalyst not only displays comparable oxygen reduction
      reaction (ORR) activity, but significantly higher electrochemical stability than
      commercial porous carbon nanosphere supported Pt catalysts (Pt/C). This robust
      electrochemical property can be due to the result of PFSA and PANI. PANI as
      protector inhibits carbon nanospheres from corrosion of carbon supports in harsh
      chemical and electrochemical conditions. Meanwhile, PFSA wrapped Pt NPs (Pt@PFSA)
      can also anchor Pt NPs on C@PANI to avoid aggregation and detachment of Pt NPs,
      due to the increased metal-support interaction caused by the strong electrostatic
      attraction between PANI and PFSA with corresponding positive and negative
      charges. Significantly, after coating PANI on carbon supports (C@PANI), almost
      all micropores in the surface of carbon disappear, effectively avoiding the
      embedding of Pt nanopaticles into micropores. Furthermore, the triple-phase
      boundary toward ORR catalysis can be facilitated by PFSA as proton conductor
      (solid electrolyte). These are of benefit to increase utilization of Pt noble
      metals and ORR activity of our new catalysts.

PMID- 28494154
TI  - Adsorption of Estrogen Contaminants by Graphene Nanomaterials under Natural
      Organic Matter Preloading: Comparison to Carbon Nanotube, Biochar, and Activated
      Carbon.
AB  - Adsorption of two estrogen contaminants (17beta-estradiol and 17alpha-ethynyl
      estradiol) by graphene nanomaterials was investigated and compared to those of a
      multi-walled carbon nanotube (MWCNT), a single-walled carbon nanotube (SWCNT),
      two biochars, a powdered activated carbon (PAC), and a granular activate carbon
      (GAC) in ultrapure water and in the competition of natural organic matter (NOM).
      Graphene nanomaterials showed comparable or better adsorption ability than carbon
      nanotubes (CNTs), biochars (BCs), and activated carbon (ACs) under NOM
      preloading. The competition of NOM decreased the estrogen adsorption by all
      adsorbents. However, the impact of NOM on the estrogen adsorption was smaller on
      graphenes than CNTs, BCs, and ACs. Moreover, the hydrophobicity of estrogens also
      affected the uptake of estrogens. These results suggested that graphene
      nanomaterials could be used to removal estrogen contaminants from water as an
      alternative adsorbent. Nevertheless, if transferred to the environment, they
      would also adsorb estrogen contaminants, leading to great environmental hazards.

PMID- 28494155
TI  - Principles for Tuning Hydrophobic Ligand-Receptor Binding Kinetics.
AB  - We investigate how to tune the rate of hydrophobic ligand-receptor association
      due to the role of solvent in adjustable receptor pockets by explicit-water
      molecular dynamics (MD) simulations. Our model considers the binding of a
      spherical ligand (key/guest) to a concave surface recess in a nonpolar wall as
      receptor (lock/host). We systematically modify the receptor's physicochemical
      properties in terms of geometry and dispersion attraction which, in turn, alter
      the water occupancy and fluctuations within the pocket. We demonstrate that even
      minor pocket modifications can lead to a significant acceleration of the water
      mediated association. For example, the binding switches from comparably slow to
      fast if the binding pocket becomes only slightly deeper. We find that the degree
      of hydrophobicity, characterized by hydration occupancy and its fluctuations,
      clearly correlates with the binding times and, for instance, links the sudden
      acceleration to an abrupt increase in hydrophobicity. For a deeper analysis based
      on passage time theory, we quantify the intimate coupling between solvent
      fluctuations and the ligand's local dynamics and friction. The coupling exhibits
      substantial nonequilibrium effects and maximizes shortly before binding, which
      slows down the binding kinetics in all cases. In summary, we rationalize how the
      physicochemical properties of a nonpolar, concave binding site tune key-lock
      binding kinetics due to water-mediated forces and fluctuations. Our study thus
      complements the profound understanding of the solvent's influence in host-guest
      binding, which is essential for tailored solutions in catalysis and
      pharmaceutical applications.

PMID- 28494156
TI  - Spatial Control of Condensation on Chemically Homogeneous Pillar-Built Surfaces.
AB  - The random nature of dropwise condensation impedes spatial control hereof and its
      use for creating microdroplet arrays, yet here we demonstrate the spatial control
      of dropwise condensation on a chemically homogeneous pillar array surface,
      yielding ~8000 droplets/mm2 under normal atmospheric pressure conditions. The
      studied pillar array surface is defined by photolithography and etched in silicon
      by deep reactive ion etching. Subsequently, the surface is covered with a self
      assembled monolayer of perfluorodecyltrichlorosilane (FDTS) to render the surface
      hydrophobic. To obtain a perfect droplet array, with one droplet per pillar, we
      exploit a phenomenon where the water vapor flux is focused on the apexes of
      surface asperities by diffusion while matching the nucleation point density to
      the array dimensions. Matching is here achieved through the variation of
      interpillar distance and vapor flow conditions.

PMID- 28494157
TI  - Side Fenestrations Provide an "Anchor" for a Stable Binding of A1899 to the Pore
      of TASK-1 Potassium Channels.
AB  - A1899 is a potent and selective inhibitor of the two-pore domain potassium (K2P)
      channel TASK-1. It was previously reported that A1899 acts as an open-channel
      blocker and binds to residues of the P1 and P2 regions, the M2 and M4 segments,
      and the halothane response element. The recently described crystal structures of
      K2P channels together with the newly identified side fenestrations indicate that
      residues relevant for TASK-1 inhibition are not purely facing the central cavity
      as initially proposed. Accordingly, the TASK-1 binding site and the mechanism of
      inhibition might need a re-evaluation. We have used TASK-1 homology models based
      on recently crystallized K2P channels and molecular dynamics simulation to
      demonstrate that the highly potent TASK-1 blocker A1899 requires binding to
      residues located in the side fenestrations. Unexpectedly, most of the previously
      described residues that interfere with TASK-1 blockade by A1899 project their
      side chains toward the fenestration lumina, underlining the relevance of these
      structures for drug binding in K2P channels. Despite its hydrophobicity, A1899
      does not seem to use the fenestrations to gain access to the central cavity from
      the lipid bilayer. In contrast, binding of A1899 to residues of the side
      fenestrations might provide a physical "anchor", reflecting an energetically
      favorable binding mode that after pore occlusion stabilizes the closed state of
      the channels.

PMID- 28494158
TI  - "Electron/Ion Sponge"-Like V-Based Polyoxometalate: Toward High-Performance
      Cathode for Rechargeable Sodium Ion Batteries.
AB  - One key challenge facing room temperature Na-ion batteries lies in identifying
      earth-abundant, environmentally friendly and safe materials that can provide
      efficient Na+ storage sites in Na-ion batteries. Herein, we report such a
      material, polyoxometalate Na2H8[MnV13O38] (NMV), with entirely different
      composition and structure from those cathode compounds reported before. Ex-situ
      XPS and FTIR analyses reveal that NMV cathode behaves like an "electron/Na-ion
      sponge", with 11 electrons/Na+ acceptability per mole, which has a decisive
      contribution to the high capacity. The extraordinary structural features,
      evidenced by X-ray crystallographic analysis, of Na2H8[MnV13O38] with a flexible
      2D lamellar network and 1D open channels provide diverse Na ion migration
      pathways, yielding good rate capability. First-principle calculations demonstrate
      that a super-reduced state, [MnV13O38]20-, is formed with slightly expanded size
      (ca. 7.5%) upon Na+ insertion compared to the original [MnV13O38]9-. This "ion
      sponge" feature ensures the good cycling stability. Consequently, benefiting from
      the combinations of "electron/ion sponge" with diverse Na+ diffusion channels,
      when revealed as the cathode materials for Na-ion batteries, Na2H8[MnV13O38]/G
      exhibits a high specific capacity (ca. 190 mA h/g at 0.1 C), associates with a
      good rate capability (130 mA h/g at 1 C), and a good capacity retention (81% at
      0.2 C). Our results promote better understanding of the storage mechanism in
      polyoxometalate host, enrich the existing rechargeable SIBs cathode chemistry,
      and enlighten an exciting direction for exploring promising cathode materials for
      Na-ion batteries.

PMID- 28494159
TI  - Association of Visual Acuity with Ocular Dominance in 2045 Myopic Patients.
AB  - PURPOSE: Previous studies of the relationship between visual acuity (VA) and
      ocular dominance have produced conflicting results. We hypothesized that (1) the
      discrepancies were related mostly to sample size and interocular visual acuity
      difference (IOVAD); (2) in large samples of individuals with marked IOVADs, the
      eye with the better uncorrected distance visual acuity (UDVA) would be dominant.
      These hypotheses were tested in a large group of myopic patients. METHODS: This
      prospective study of cycloplegic refraction involved 2045 myopic refractive
      surgery candidates. Patients with amblyopia or strabismus were excluded. Ocular
      dominance was assessed using the hole-in-the-card test. RESULTS: In 2045
      patients, the dominant eye had significantly better UDVA (p = 0.028) and was less
      astigmatic (p = 0.000) than the nondominant eye. In 426 patients with marked
      interocular difference in the UDVA (>=0.2 logMAR), the dominant eye not only had
      significant UDVA (p = 0.022) but also significantly less myopic (p = 0.028) and
      had a shorter axial length (AL; p = 0.001). In patients with smaller differences
      in UDVA (0.1 logMAR, n = 411) or no difference (n = 1208), the dominant and
      nondominant eyes did not differ significantly with respect to UDVA, myopic power,
      and AL (p > 0.05). CONCLUSIONS: The present study showed that the dominant eyes
      had significantly better UDVA than the nondominant eyes, especially in
      individuals with marked differences in UDVA. These results supported our
      hypothesis regarding the relationship between better VA and ocular dominance.

PMID- 28494160
TI  - Forensic Psychological Assessment in Forensic Practice: Case Studies.

PMID- 28494161
TI  - The Anxiety Depression Distress Inventory-27 (ADDI-27): New Evidence of Factor
      Structure, Item-Level Measurement Invariance, and Validity.
AB  - Three studies examining the factor structure and psychometric properties of the
      Anxiety Depression Distress Inventory-27 (ADDI-27) extended the initial
      instrument development studies for this recently introduced inventory. The ADDI
      27 is an empirically derived short form of the Mood and Anxiety Questionaire-90
      (MASQ-90) comprising three scales: Positive Affect, Somatic Anxiety, and General
      Distress. The main objectives of Study 1 (N = 700) were to examine the factor
      structure of the ADDI-27 and its measurement invariance across gender at the item
      level. The objective of Study 2 (N = 538) was to examine evidence for the
      convergent and discriminant validity of scores on the ADDI-27. The objective of
      Study 3 (N = 240) was to assess further evidence for the nomological network and
      convergent and discriminant validity of the ADDI-27 scores. Results of
      exploratory structural equation modeling yielded strong support for a 3-factor
      model, with approximate fit indexes meeting or exceeding the conventional
      cutoffs. With p <= .001 as the criterion for detecting noninvariance, results of
      measurement invariance analysis suggested that all of the ADDI-27 items were
      invariant across gender. Results of multivariate validity analyses across 2
      studies provided support for the convergent and discriminant validity of scores
      on the ADDI-27 scales.

PMID- 28494162
TI  - Are automatic systems the future of motorcycle safety? A novel methodology to
      prioritize potential safety solutions based on their projected effectiveness.
AB  - OBJECTIVE: Motorcycle riders are involved in significantly more crashes per
      kilometer driven than passenger car drivers. Nonetheless, the development and
      implementation of motorcycle safety systems lags far behind that of passenger
      cars. This research addresses the identification of the most effective motorcycle
      safety solutions in the context of different countries. METHODS: A knowledge
      based system of motorcycle safety (KBMS) was developed to assess the potential
      for various safety solutions to mitigate or avoid motorcycle crashes. First, a
      set of 26 common crash scenarios was identified from the analysis of multiple
      crash databases. Second, the relative effectiveness of 10 safety solutions was
      assessed for the 26 crash scenarios by a panel of experts. Third, relevant
      information about crashes was used to weigh the importance of each crash scenario
      in the region studied. The KBMS method was applied with an Italian database, with
      a total of more than 1 million motorcycle crashes in the period 2000-2012.
      RESULTS: When applied to the Italian context, the KBMS suggested that automatic
      systems designed to compensate for riders' or drivers' errors of commission or
      omission are the potentially most effective safety solution. The KBMS method
      showed an effective way to compare the potential of various safety solutions,
      through a scored list with the expected effectiveness of each safety solution for
      the region to which the crash data belong. A comparison of our results with a
      previous study that attempted a systematic prioritization of safety systems for
      motorcycles (PISa project) showed an encouraging agreement. CONCLUSIONS: Current
      results revealed that automatic systems have the greatest potential to improve
      motorcycle safety. Accumulating and encoding expertise in crash analysis from a
      range of disciplines into a scalable and reusable analytical tool, as proposed
      with the use of KBMS, has the potential to guide research and development of
      effective safety systems. As the expert assessment of the crash scenarios is
      decoupled from the regional crash database, the expert assessment may be
      reutilized, thereby allowing rapid reanalysis when new crash data become
      available. In addition, the KBMS methodology has potential application to injury
      forecasting, driver/rider training strategies, and redesign of existing road
      infrastructure.

PMID- 28494163
TI  - Expression of 14-3-3 Zeta Protein in Dexamethasone-Treated Mice and Human TM-1
      Cells.
AB  - PURPOSE: 14-3-3 zeta protein plays a potential protective role in
      neurodegenerative disease. Given that glaucoma and neurodegenerative diseases
      share a similar pathogenesis, it is possible that 14-3-3 zeta may have a similar
      protective effect in the glaucomatous process. In the present study, we measured
      the expression of 14-3-3 zeta in vivo (mouse eyes) and in vitro in a transformed
      human trabecular meshwork (HTM) cell line, TM-1, and assessed the possible roles
      of this protein in dexamethasone (DEX)-treated eyes and HTM cells. METHODS: Mouse
      eyes were randomly treated with 0.1% dexamethasone (DEX) eye drops or phosphate
      buffered solution (PBS) for 28 days. The expression and distribution of 14-3-3
      zeta protein in mouse eyes were examined using immunofluorescence. TM-1 cells
      were treated with DEX (10-6 or 10-7 M) or PBS for 1, 4, or 7 days, and the mRNA
      and protein expression of 14-3-3 zeta were detected by real-time RT-PCR and
      Western blotting. RESULTS: 14-3-3 zeta protein was highly expressed in the mouse
      cornea, trabecular meshwork (TM), and ciliary body. Intraocular pressure (IOP)
      was significantly elevated, whereas the 14-3-3 zeta expression was significantly
      decreased in mouse TM after 0.1% DEX treatment for 28 days. In vitro, treatment
      with 10-7 M DEX mildly increased 14-3-3 zeta mRNA and protein expression (p >
      0.05), whereas 10-6 M DEX significantly decreased expression of 14-3-3 zeta mRNA
      and protein (p < 0.05) compared to the control (Ctrl) group at the seventh day.
      CONCLUSIONS: DEX can increase IOP in mouse eyes and concurrently downregulate 14
      3-3 zeta protein expression in mouse TM. The effects of DEX on 14-3-3 zeta
      expression in vitro were both dose- and time-related. Our results suggest that
      alterations in 14-3-3 zeta protein may be implicated in DEX-induced pathological
      elevated IOP.

PMID- 28494164
TI  - Effects of enhancing vitamin D status by 25-hydroxycholecalciferol
      supplementation, alone or in combination with calcium and phosphorus, on sternum
      mineralisation and breast meat quality in broilers.
AB  - 1. The aim of the present study was to examine the effects of improving vitamin D
      status in broiler diets by supplementary 25-hydroxycholecalciferol (25OHD3),
      alone or in combination with calcium (Ca) and available phosphorus (aP), on live
      performance, sternum mineralisation and breast meat quality in broilers. 2. A
      total of 936 1-d-old Ross 308 broilers were used in the study. After gender
      determination at the hatchery, chicks from each sex were randomly distributed
      into three dietary treatments. The following dietary treatments were used in the
      experiment from hatch to 38 d: (1) A control diet formulated to meet all of the
      nutrient requirements of broiler chicks according to the management guide; (2)
      The control diet supplemented with 18.7-15.0 ug/kg of 25OHD3; and (3) The control
      diet supplemented with 18.7-15.0 ug/kg of 25OHD3 plus Ca + aP. 3. Improvement in
      vitamin D status by 25OHD3 supplementation, alone or in combination with Ca and
      aP, had no effect on body weight and feed conversion ratio of broilers. 4. The
      serum 25OHD3 concentration significantly increased with 25OHD3 and 25OHD3 plus Ca
      + aP supplementation (P < 0.05), whereas the ionised Ca and Mg concentrations
      remained unchanged. 5. Sternum absolute weight, ash content and the
      concentrations of Ca and P significantly increased (P < 0.01) with
      supplementation of 25OHD3, alone or in combination with Ca + aP. 6. Supplemental
      25OHD3, alone or in combination with Ca + aP, slightly increased pH24 (P = 0.05)
      and decreased (P < 0.01) squeezable water loss in breast meat, whereas it had no
      significant effect on lightness, yellowness and sarcoplasmic protein solubility.
      7. In conclusion, the results suggested that enhancing vitamin D status by 25OHD3
      supplementation alone or in combination with Ca + aP may improve sternum
      structure and mineral accretion. Furthermore, supplemental 25OHD3, even in a
      nutritionally complete diet, may offer an effective way to improve protein
      solubility in female broilers.

PMID- 28494165
TI  - Effect of feed supplementation with Satureja khuzistanica essential oil on
      performance and physiological parameters of broilers fed on wheat- or maize-based
      diets.
AB  - 1. The aim of this study was to evaluate various levels of Satureja khuzistanica
      essential oil (SKEO) on performance and physiological parameters of broilers fed
      on wheat- or maize-based diets. 2. Treatments consisted of two cereals (maize- or
      wheat-based diets) and three levels of SKEO)0, 250 and 500 mg/kg). 3. Feed intake
      (FI) and body weight gain (BWG) decreased in broilers fed on the wheat-based
      diets compared to the control diet. Dietary supplementation of 500 mg/kg SKEO
      increased FI and BWG. Dietary SKEO supplementation was effective in improving FI
      and BWG only in wheat-based diets and was effective in improving feed conversion
      ratio (FCR) in both diets. 4. Dietary supplementation of 500 mg/kg SKEO caused a
      significant decrease in plasma cholesterol and triglycerides. Also, plasma low
      density lipoprotein concentration was decreased in broilers fed on 250 and 500
      mg/kg of SKEO. Plasma cholesterol levels in birds fed on the wheat-based diets
      were lower than in those fed on maize-based diets. 5. Dietary supplementation of
      500 mg/kg SKEO increased caecal population of Lactobacillus and reduced total
      bacterial and Escherichia coli count. Caecal population of Lactobacillus
      decreased in broilers fed on the wheat-based diets. 6. Digesta viscosity was
      increased in broilers fed on the wheat-based diets and decreased in broilers fed
      on 500 mg/kg SKEO compared to the control diet. Dietary SKEO supplementation was
      effective in reducing digesta viscosity values only in wheat-based diets. 7.
      Villus height of the duodenum and jejunum decreased in broilers fed on the wheat
      based diets. Dietary supplementation of 500 mg/kg SKEO increased villus height
      and villus height-to-crypt depth ratios and decreased crypt depth of the duodenum
      compared to the control diet. 8. It can be concluded that dietary SKEO
      supplementation was effective in improving FI, BWG and FCR values in wheat-based
      diets.

PMID- 28494166
TI  - Ocular Safety of Intravitreal Connective Tissue Growth Factor Neutralizing
      Antibody.
AB  - PURPOSE: To detect the safety of intravitreal injection of anti-connective tissue
      growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing
      antibody for experimental animal studies. METHODS: Forty-five Lister Hooded male
      pigmented rats were divided into five groups that received IVAC (2 MUl)
      corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 MUg/ml (E), equal
      to 1.25, 2.5, 6.25, and 12.5 ug/ml of antibody concentration in rat vitreous,
      respectively. The sham group (A) received 2 MUl of normal saline. Full field
      electroretinography (ERG) was performed at baseline and on days 7 and 28 after
      IVAC. The animals were euthanized and the corresponding eyes were subjected to
      routine histopathology, immunohistochemistry for glial fibrillary acidic protein
      (GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay. RESULTS:
      Scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89
      +/- 71.2 and 178.57 +/- 55.58 MUV, respectively, at baseline which significantly
      reduced to 79.31 +/- 52.59 and 128.73 +/- 41.61 MUV, respectively, after 28 days
      in group E (p < 0.05). There was no significant reduction of amplitudes in other
      groups with lower doses of anti-CTGF antibody. Retinal ganglion cells were
      significantly decreased in group E as compared to other groups. GFAP immune
      reactivity was not significant in any of the groups. TUNEL test showed inner
      retinal neural cell apoptosis only in group E. CONCLUSIONS: ERG, histopathologic,
      and apoptotic assays revealed no toxic effects of 10-50 MUg/ml of IVAC in rat
      eyes. Using 100 MUg/ml IVAC led to a significant toxic effect in terms of
      functional, histopathologic, and TUNEL findings.

PMID- 28494167
TI  - "My Whole Life is Ethics!" Ordinary Ethics and Gene Therapy Clinical Trials.
AB  - What and where is ethics in gene therapy? Historical debates have identified a
      set of ethical issues with the field, and current regulatory systems presume a
      discrete ethics that can be achieved or protected. Resisting attempts at
      demarcation or resolution, we use the notions of "ordinary" or "everyday" ethics
      to develop a better understanding of the complexities of experimental gene
      therapy for patients, families, and practitioners and create richer imaginings of
      ethics in the gene therapy sphere. Drawing on ethnographic research in several
      clinical trials, we show that patients/parents can acquire some control in
      difficult medical situations, and practitioners can attune their care to their
      patients' needs. The human provenance of gene therapy practice, and the
      irreducible sociality of ethics, means that understanding the ethics of this
      medical field also requires understanding the everyday worlds and relationships
      of those at its heart.

PMID- 28494168
TI  - Uveal Melanoma Risk Factors: A Systematic Review of Meta-Analyses.
AB  - PURPOSE: There is currently no clinical risk-assessment tool allowing
      identification of patients at risk for developing uveal melanoma (UM) who might
      benefit from regular screening. As a first step toward the elaboration of such a
      tool, we systematically reviewed UM risk factors already established by meta
      analysis. METHODS: Two reviewers independently screened Pubmed, Medline, Embase,
      and Web of Science from their respective inception dates until July 2016 using a
      combination of keywords and MeSH terms. Eligible studies were meta-analyses or
      systematic reviews providing pooled odds ratios (ORs) of risk factors for UM
      development or sufficient information to calculate them. Methodological quality
      was evaluated using the Assessment of Multiple Systematic Reviews tool. RESULTS:
      Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%;
      max: 72.7%) were included. The following significant risk factors were
      identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10-7.26), welding (OR
      2.05, 95% CI 1.20-3.51), occupational cooking (OR 1.81, 95% CI 1.33-2.46), fair
      skin color (OR 1.80, 95% CI 1.31-2.47), light eye color (OR 1.75, 95% CI 1.31
      2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27-2.39), propensity to sunburn
      (OR 1.64, 95% CI 1.29-2.09), iris nevi (OR 1.53, 95% CI 1.03-2.27), and cutaneous
      freckles (OR 1.27, 95% CI 1.09-1.49). Non-significant factors included outdoor
      leisure activity, occupational sunlight exposure, latitude of birth, and hair
      color. CONCLUSION: Moderate quality of evidence determined nine significant risk
      factors for developing UM. Knowledge of these variables will assist researchers
      in the elaboration of a formal risk-assessment tool allowing clinicians to
      estimate susceptibility to the disease and necessity of regular screening.

PMID- 28494169
TI  - Companion Animals in Natural Disasters: A Scoping Review of Scholarly Sources.
AB  - During a disaster, people may make evacuation decisions based on their companion
      animal's welfare, therefore exposing themselves, their companion animals, and
      emergency responders to increased risk for injury or death. The loss and
      suffering of companion animals in disasters causes deep distress, diminishing
      people's capacity to rebuild their lives. This scoping review presents scholarly
      research studies and reviews relating to people and their companion animals in
      the context of disasters, with an aim of informing researchers, policymakers, and
      practitioners and providing direction for future research. Using the Arksey and
      O'Malley framework, articles in scholarly journals from 2004 to 2014 are
      discussed. Analysis included 38 articles: 20 research studies, 12 reviews, and 6
      editorials. Findings revealed 2 central themes: companion animals as a risk
      factor to human health and safety and companion animals being "at risk"
      themselves. An emerging theme was "responsibility": Who is responsible for
      companion animals in disasters and how? Understanding the implications of human
      nonhuman animal relationships for disaster response and having a broader public
      consensus on what is owed to animals at times of emergency are important to
      community preparedness and resilience.

PMID- 28494170
TI  - Why High-Intensity NPPV is Favourable to Low-Intensity NPPV: Clinical and
      Physiological Reasons.
AB  - High-intensity non-invasive positive pressure ventilation (NPPV) was originally
      described for chronic hypercapnic chronic obstructive pulmonary disease (COPD)
      patients in 2009, and refers to a specific ventilatory approach whereby NPPV
      settings are aimed at achieving the lowest arterial partial pressure of carbon
      dioxide (PaCO2) values possible. Thus, high-intensity NPPV requires ventilator
      settings to be increased in a stepwise approach to either an individually
      tolerated maximum, or to the levels necessary to achieve normocapnia. This
      differs from the classic approach to low-intensity NPPV, which comprises
      considerably lower ventilator settings and typically fails to lower elevated
      PaCO2 values. The ongoing discussion about whether or not long-term NPPV should
      be used in chronic hypercapnic COPD patients is based on the observation that
      many studies in the last two decades have failed to provide evidence for this
      particular patient cohort. In addition, these trials preferably used low
      intensity NPPV. There is now, however, increasing evidence to suggest that high
      intensity NPPV is capable of improving important physiological parameters such as
      blood gases and lung function, as well as health-related quality of life.
      Moreover, this approach also produced positive outcomes following two recent
      randomized controlled trials, e.g., improved survival rates in stable COPD
      patients, and admission-free survival in patients with persisting hypercapnia
      following acute in-hospital NPPV to treat acute acidotic respiratory failure. As
      a consequence, the time has now come to evaluate the impact of long-term NPPV on
      both the physiological and clinical outcomes, with emphasis on the different
      approaches to NPPV. Therefore, the aim of the current review article is to
      elaborate on the clinical and physiological reasons for why high-intensity NPPV
      is favourable to low-intensity NPPV.

PMID- 28494172
TI  - An investigation of clear speech effects on articulatory kinematics in talkers
      with ALS.
AB  - Amyotrophic lateral sclerosis (ALS) affects the speech motor system and causes a
      substantial decline in intelligibility. Clear speech strategies have been found
      to benefit intelligibility in talkers with dysarthria and the purpose of this
      study was to examine clear speech effects on tongue, lip, and jaw movements in
      persons with ALS and healthy controls. For this purpose, participants produced 10
      repetitions of the sentence 'I owe you a yoyo' using both habitual and clear
      speech. Movement variability as well as maximum speed, range, and duration of
      movement of the articulators were obtained for both conditions. The results show
      significantly lower jaw movement variability during habitual speech but greater
      variability for clear speech in ALS relative to controls. The kinematic data was
      consistent with expectations for individuals with dysarthria. Based on these
      results, clear speech may be considered a mode of speech that produces high
      movement variability in talkers with ALS.

PMID- 28494171
TI  - Zinc oxide nanoparticles antagonize the effect of Cetuximab on head and neck
      squamous cell carcinoma in vitro.
AB  - Zinc oxide nanoparticles (ZnO-NPs) are being used in many cosmetic products and
      have been shown to induce tumor-selective cell death in human head and neck
      squamous cell carcinoma (HNSCC) in vitro. Cetuximab is a monoclonal antibody
      directed against the epidermal growth factor receptor (EGFR), whose effectiveness
      for HNSCC, alone or in combination with cytostatic drugs, has been demonstrated
      intensively in the last decades. Nanoparticles are known to interact with protein
      structures and thus may influence their functionality. The aim of the current
      study was to evaluate the effect of ZnO-NPs on the antitumor properties of
      Cetuximab in HNSCC in vitro. Two HNSCC cell lines (FaDu and HLaC-78) were treated
      with 0.1, 1 or 10 MUM Cetuximab as well as 0, 0.1 or 1 MUg/ml ZnO-NP. Qualitative
      assessment of ZnO-NP was conducted via transmission electron microscopy (TEM) and
      immunofluorescence staining. Evaluation was done via the MTT-assay after 24, 48
      and 72 hours of incubation with Cetuximab and ZnO-NPs. ZnO-NPs were shown to
      antagonize the anti-tumor effects of Cetuximab in a time-dependent as well as
      dose-dependent way. These findings suggest an inhibitory interaction of ZnO-NPs
      with Cetuximab, which warrants further investigation.

PMID- 28494173
TI  - Suicide attempt with acetonitrile ingestion in a nursing mother.
AB  - CONTEXT: Acetonitrile (ACN) is a solvent rapidly absorbed through lungs and
      intestinal tract, and is slowly metabolized to cyanide (CN) by enzymatic
      processes mediated by CYP2E1. OBJECTIVE: To describe the clinical and laboratory
      evolution, ACN elimination half-life, and its presence in breast milk in a
      nursing mother who attempted suicide. CASE DETAILS: A 25-year-old 2-month nursing
      mother ingested an estimated dose of 2.1 g/kg of ACN. Blood and urine samples
      were collected 24 h later for ACN, CN and thiocyanate analysis, and 12.5 g sodium
      thiosulfate i.v. in 1-h infusion was started and repeated every 24 h for 4 days.
      ACN results showed 200 mg/L in blood and 235 mg/L in urine. ACN analysis in the
      breast milk at Day 6 showed level of 21 mg/L compared to 27 mg/L in blood
      collected at the same time, suggesting a possible relationship of 1.3:1.0 ratio.
      An elimination half-life of 40.4 h was calculated, compared to 32 and 36 h showed
      in other studies. DISCUSSION: The clinical management must involve the use of CN
      antidotes for more than 24 h depending on the symptoms and blood levels of ACN.
      Furthermore, our data showed the possible existence of a close relationship
      between plasma and breast milk levels.

PMID- 28494174
TI  - Human endometrial stromal cell plasticity: Reversible sFlt1 expression negatively
      coincides with decidualization.
AB  - Preeclampsia (PE) is a major complication of pregnancy in which the placenta is
      known to have shallow implantation into the uterine decidua. Studies have
      implicated soluble fms-like tyrosine kinase-1 (sFlt1), a soluble vascular
      endothelial growth factor (VEGF) receptor protein, in the pathogenesis of PE.
      sFlt1 has the ability to bind to and neutralize the angiogenic functions of VEGF
      and placental growth factor (PlGF). The presence of sFlt1 and its action in the
      endometrium is yet to be determined. We hypothesize that endometrial stromal
      cells (ESC) at the maternal-fetal interface may play a role in sFlt-1 regulation
      during pregnancy. In this study, we seek to understand the dynamic regulation of
      sFlt1 production in primary human ESC as a result of hormone stimulation and
      withdrawal. To mimic a biphasic menstrual cycle, ESC were treated with cAMP to
      induce endometrial decidualization that occurs during the luteal secretory phase,
      followed by cAMP withdrawal reflecting the follicular proliferative phase. Here,
      we present data to show that (1) ESC produce detectable amounts of sFlt1, (2)
      sFlt1 expression is turned off during decidualization at both the protein and RNA
      level (3) ESC decidualization and resulting sFlt1 expression are reversible
      phenomenon, and (4) Decidualization markers prolactin (PRL) and VEGF expressions
      in ESC are negatively correlated with sFlt1. These findings may have important
      implications in diseases such as PE that involve abnormal decidualization,
      implantation and angiogenesis at the maternal-fetal interface.

PMID- 28494175
TI  - The effect of plasmapheresis on treating disseminated intravascular coagulation
      (DIC) caused by a Hemiscorpius lepturus (Gadim) sting.
AB  - INTRODUCTION: The highest mortality from scorpion stings in Iran is due to the
      stings of a particular type of scorpion known as Hemiscorpius lepturus (H.
      lepturus, Gadim in local language). The present study aimed at investigating the
      use of plasmapheresis to treat severe cases of H. lepturus stings. METHOD: This
      pilot study was a randomized clinical trial conducted from June 2015 to June 2016
      in Razi hospital of Ahvaz, Iran. Twenty-nine patients who had been stung by H.
      lepturus and admitted to ICU because of disseminated intravascular coagulation
      (DIC) were randomly assigned into control (15 patients, supportive treatments)
      and plasmapheresis (14 patients, supportive treatments + plasmapheresis) groups,
      and the patient outcomes were compared between the two groups. FINDINGS: Eighteen
      patients were female (62%), and the mean of patient age was 24 +/- 7. Most of the
      sting cases had occurred in the torso (15 patients, 52%). Only 10 patients (34%)
      arrived in the hospital within 12 h of being stung. There was no significant
      difference between the two groups in terms of the demographic and sting features.
      In the plasmapheresis group, hemoglobin level was significantly lower, while the
      PT and INR were measurably higher. In total, the plasmapheresis group experienced
      29 sessions of treatment (an average of two sessions for each patient). Overall,
      19 patients (66%) expired, whereas 10 patients (34%) experienced recovery with or
      without complications. The rate of recovery was significantly higher in the
      plasmapheresis group compared with controls, with eight patients (57%) in the
      plasmapheresis group surviving compared with two (14%) in the control group
      (p=.045). The duration of hospitalization was higher in the plasmaphersis group
      (p < .001). A comparison of the dead and recovered patients' features indicated
      that the dead patients arrived in the hospital significantly later than the
      recovered ones, and they also had lower platelet counts. CONCLUSIONS: The
      findings of this small-scale pilot study show that using plasmapheresis in
      treating DIC in patients stung by H. lepturus can prevent death and encourage
      recovery. However, prior to using plasmapheresis as a routine treatment for
      severe cases of people stung by this scorpion or other similar ones, further
      controlled studies with a larger sample size are needed.

PMID- 28494177
TI  - Influence of low-level laser on pain and inflammation in type 2 diabetes mellitus
      with diabetic dermopathy - A case report.
AB  - Numerous skin lesions have been commonly observed in individuals with diabetes
      mellitus. The common skin manifestations of diabetes mellitus are erythrasma,
      xanthomatosis, xanthelasma, phycomycetes and cutaneous infections like
      furuncolosis, candidiasis, carbuncle, dermatophytosis, etc. Diabetic dermopathy
      is the most common skin lesion found in patients with diabetes. It is typically
      seen in men aged above 50 years. In low-level laser therapy (LLLT), the entire
      lower limb was illuminated with the frequency of 20 Hz and wavelength of 830 nm
      for 9 min, and the treatment was divided into four parts. With the continued
      sessions of LLLT, the skin manifestations and neuropathy conditions improved
      drastically. On the 21st day, the skin colour was found to be normal. Also, there
      were significant changes in clinical findings for diabetic peripheral neuropathy.
      LLLT with specific exercises can promote healing of skin manifestations in
      individuals with type 2 diabetes mellitus. It can be used as an effective
      treatment modality for treating diabetic dermopathy.

PMID- 28494176
TI  - Comparative analysis of the effects of a sphingosine kinase inhibitor to
      temozolomide and radiation treatment on glioblastoma cell lines.
AB  - Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment
      of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell
      heterogeneity. Accordingly, there is a need to target alternative molecules
      enhancing specific GBM autocrine or paracrine mechanisms and amplifying the
      effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid
      target molecule with an important role in cell invasion and proliferation.
      Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased
      production of reactive oxygen species (ROS), which may potentiate radiation
      cytotoxicity. We analyzed the effect of SKI singular versus combined treatments
      with TMZ and radiation on 2 human GBM cell lines characterized by a lack of MGMT
      expression and low or high expression of the anti-oxidant enzyme, glutathione
      peroxidase 1 (GPx1). Effects were drug concentration-, cell line-dependent and
      partly ROS-mediated. Clonogenic survival assay demonstrates that SKI was more
      effective than TMZ in increasing the sensitivity of U87 cells, which express low
      GPx1 amount, to a 2 Gy X-ray dose. Addition of both SKI and TMZ drastically
      decreased U87 cells survival compared with the combination
      temozolomide/radiation. SKI less effectively than TMZ sensitized LN229 cells to
      the 2 Gy X-ray dose. Its combination to TMZ in absence of irradiation was as
      efficient as TMZ combination with X-ray. We provide first evidence for SKI as an
      alternative or complementary treatment to TMZ, and for efficient combinations of
      low doses of drugs and X-ray. These may help as novel bi-modal and tri-modal
      therapies to contend with GBM heterogeneity.

PMID- 28494178
TI  - Suicide attempt with self-made Taxus baccata leaf capsules: survival following
      the application of extracorporeal membrane oxygenation for ventricular arrythmia
      and refractory cardiogenic shock.
AB  - CONTEXT: Yew intoxication has been known for many years; high dose ingestion of
      Taxus baccata leads to cardiac toxicity mediated by calcium and sodium channel
      blocking properties. We present a case report of a patient who attempted suicide
      after T. baccata ingestion, causing refractory cardiogenic shock requiring
      temporary circulatory assistance by veno-arterial extra corporeal membrane
      oxygenation (VA ECMO). CASE DETAILS: A 28-year-old man was admitted to the
      critical care unit of a university hospital for arrhythmia after ingestion of
      self-made T. baccata leaf capsules. He rapidly developed cardiovascular collapse
      requiring mechanical ventilation, high dose intravenous catecholamines and
      electrical cardioversion. A femoro-femoral VA ECMO was implanted due to severe
      biventricular dysfunction and ventricular arrhythmia, associated with continuous
      renal replacement therapy. Taxol A, taxol B and baccatin III were detected and
      measured in both blood and urine samples by high-performance liquid
      chromatography tandem mass spectrometry, and kinetics suggested urinary
      excretion. Two days after hospital admission, VA ECMO and continuous renal
      replacement therapy were removed with full recovery of cardiac function.
      DISCUSSION: Our experience suggests that circulatory assistance by VA ECMO and
      continuous renal replacement therapy seem to be effective safe second-line
      therapeutic options in critically ill cases of severe yew intoxication with
      refractory cardiogenic shock due to arrhythmia.

PMID- 28494179
TI  - Predictive biomarkers for triple negative breast cancer treated with platinum
      based chemotherapy.
AB  - Treatment of triple negative breast cancer (TNBC) has been a big challenge since
      it is defined. To date, platinum-based chemotherapy has played a significant role
      in the treatment of TNBC patients. However, some patients do not respond to
      platinum salts or gradually develop chemoresistance, resulting in little effect,
      or even some adverse effects. Here, we review numerous preclinical and clinical
      investigations to summarize possible mechanisms and potential predictive
      biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD)
      resulting from the loss of BRCA function is the main rationale of platinum
      efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be
      important potential biomarkers. Based on genome-wide effects, BRCA-like
      classifier can identify the functional loss of BRCA and work as the predictor.
      HRD score that is able to identify the "BRCAness" and predict the sensitivity of
      platinum is increasingly considered. Taken together, all findings suggest that HR
      deficiency profile encompassed by BRCA mutation and high HRD score could predict
      response to platinum, even to other DNA-damage inducing agents. p53 family
      members and molecular subtypes of TNBC are also important alternative
      considerations for predicting platinum response based on the preclinical trials.
      Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging
      as predictive biomarkers.

PMID- 28494181
TI  - Characterization of Asthma-Chronic Obstructive Pulmonary Disease Overlap
      Syndrome: A Qualitative Analysis.
AB  - Approximately 15-20% of patients with chronic obstructive pulmonary disease
      (COPD) also display characteristics of asthma. In May 2014, the asthma-COPD
      overlap syndrome (ACOS) was briefly addressed in the Global Initiative for Asthma
      (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy
      documents. We evaluated how pulmonologists diagnose and treat ACOS and how they
      assess its control. Pulmonologists from two university healthcare centers, having
      >= 1 year experience, treating patients with asthma, COPD, or ACOS, were invited
      to participate in focus groups. Two focus groups (1 hour duration) were convened
      with seven and five participants, respectively. According to pulmonologists from
      both institutions, ACOS is a new name for an existing syndrome rather than a new
      disease. It is characterized by incomplete reversible airflow limitations and
      changes in forced expiratory volume in one second over time. The pulmonologists
      noted that its diagnosis must be based on clinical characteristics, pulmonary
      function test results, and clinical intuition. To diagnose ACOS, pulmonologists
      must rely on their clinical judgment. They also agreed that the treatment of
      patients with ACOS should target the features of both asthma and COPD.
      Pulmonologists from both institutions used asthma control criteria to assess ACOS
      control. A deeper understanding would enable clinicians to establish specific
      criteria for the diagnosis, treatment, and follow-up of subjects with ACOS.

PMID- 28494180
TI  - Intra-arterial administration of tumor-targeting Salmonella typhimurium A1-R
      regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived
      orthotopic xenograft (PDOX) mouse model.
AB  - Previously, a patient-derived orthotopic xenograft (PDOX) model was established
      with a lung metastasis from an osteosarcoma patient which developed after
      adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated
      the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In
      the present report, osteosarcoma tissue was implanted orthotopically in the
      distal femur of mice which were randomized into the following groups when tumor
      volume reached approximately 100 mm3; On day 14 after initiation of treatment,
      all but CDDP significantly inhibited tumor volume growth compared with untreated
      controls. Control (G1): 793.7 +/- 215.0 mm3; CDDP (G2): 588.1 +/- 176.9 mm3;
      Salmonella typhimurium A1-R (S. typhimurium A1-R) intravenous (i.v.) (G3): 269.7
      +/- 72.7 mm3; S. typhimurium A1-R intra-arterial (i.a.) (G4): 70.2 +/- 18.9 mm3
      (CDDP: p = 0.056; S. typhimurium A1-R i.v.: p = 0.0001; S. typhimurium A1-R i.a.:
      p = 0.00003, all vs. untreated controls). i.a. administration of S. typhimurium
      A1-R was significantly more effective than either CDDP (p = 0.00007), or i.v.
      administration of S. typhimurium A1-R (p = 0.00007) and significantly regressed
      the tumor volume compared with day 0 (p = 0.001). The new model of i.a.
      administration of S. typhimurium A1-R has great promise for the treatment of
      recalcitrant osteosarcoma.

PMID- 28494182
TI  - FabG can function as PhaB for poly-3-hydroxybutyrate biosynthesis in
      photosynthetic cyanobacteria Synechocystis sp. PCC 6803.
AB  - The production of poly-3-hydroxybutyrate (PHB) by photosynthetic cyanobacteria is
      a potentially sustainable production method for the biodegradable plastics
      industry. beta-Ketoacyl-ACP reductase (FabG), from the photosynthetic
      cyanobacterium Synechocystis sp. PCC 6803 (SpFabG), is the first NADPH-dependent
      reductase in the fatty acid biosynthesis pathway. Its structure is similar to
      that of acetoacetyl-CoA reductase (SpPhaB), which is critical for PHB synthesis
      and can replace SpPhaB for acetoacetyl-CoA reduction in vitro. However, the
      specific function of SpFabG in fatty acid synthesis and whether SpFabG could
      participate in PHB synthesis in vivo were not yet clear. In this study, the role
      of SpFabG in fatty acid synthesis was first verified in vivo by knocking down and
      overexpressing of fabG. It was shown that SpFabG was essential yet not rate
      limiting for fatty acid biosynthesis. The biochemical characterization of SpFabG
      using acetoacetyl-CoA as the substrate showed that the optimum temperature,
      optimum pH, Km and kcat were 30 degrees C, 7, 2.30 mM, and 19.85 s-1,
      respectively, which exemplified the ability of SpFabG to reduce acetoacetyl-CoA
      with a relatively low affinity and weak catalytic efficiency. Functional analysis
      of SpFabG in vivo indicated that SpFabG was able to partially complement SpPhaB
      under nitrogen-deprived conditions, and overexpression of fabG led to the
      diversion of partial carbon flux from fatty acid toward PHB synthesis.

PMID- 28494183
TI  - Resolution of cannabis hyperemesis syndrome with topical capsaicin in the
      emergency department: a case series.
AB  - BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms
      of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged
      cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may
      be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS;
      it binds TRPV1 with high specificity, impairing substance P signaling in the area
      postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may
      explain its apparent antiemetic effect in this syndrome. PURPOSE: We describe a
      series of thirteen cases of suspected cannabis hyperemesis syndrome treated with
      capsaicin in the emergency departments of two academic medical centers. METHODS:
      A query of the electronic health record at both centers identified thirteen
      patients with documented daily cannabis use and symptoms consistent with CHS who
      were administered topical capsaicin cream for symptom management. RESULTS: All 13
      patients experienced symptom relief after administration of capsaicin cream.
      CONCLUSION: Topical capsaicin was associated with improvement in symptoms of CHS
      after other treatments failed.

PMID- 28494184
TI  - Current status of research and treatment for non-small cell lung cancer in never
      smoking females.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide with over 1
      million deaths each year. The overall prognosis of lung cancer patients remains
      unsatisfactory, with a 5-year overall survival rate of less than 15%. Although
      most lung cancers are a result of smoking, approximately 25% of lung cancer cases
      worldwide are not attributable to tobacco use. Notably, more than half of the
      lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer
      (NSCLC) cases, cigarette-smokers have a greater association with squamous cell
      carcinoma than adenocarcinoma, which is more common in non-smokers. These
      findings imply that specific molecular and pathological features may associate
      with lung adenocarcinoma arising in non-smoker female patients. Over the past
      decade, whole genome sequencing and other '-omics' technologies led to the
      discovery of pathogenic mutations that drive tumor cell formation. These
      technological developments may enable tailored patient treatments throughout the
      course of their disease, potentially leading to improved patient outcomes. Some
      clinical and laboratory studies have shown success outcomes using epidermal
      growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine
      kinase inhibitors (TKI) in patients with EGFR mutations and ALK rearrangements,
      respectively. In fact, these 2 mutations are predominantly present in female non
      smokers with adenocarcinoma. Immunotherapy has also recently emerged as a major
      therapeutic modality in NSCLC. In this review, we summarize the current
      understanding of NSCLC biology and new therapeutic molecular targets, focusing on
      the pathogenesis of non-smoker female NSCLC patients.

PMID- 28494185
TI  - Functional analysis of rare variants in mismatch repair proteins augments results
      from computation-based predictive methods.
AB  - The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA
      mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6, and PMS2. A major
      challenge for clinical diagnosis of LS is the frequent identification of variants
      of uncertain significance (VUS) in these genes, as it is often difficult to
      determine variant pathogenicity, particularly for missense variants. Generic
      programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON
      MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS
      in MMR genes. We evaluated the performance of multiple predictive programs in the
      context of functional biologic data for 15 VUS in MLH1, MSH2, and PMS2. Using
      cell line models, we characterized VUS predicted to range from neutral to
      pathogenic on mRNA and protein expression, basal cellular viability, viability
      following treatment with a panel of DNA-damaging agents, and functionality in DNA
      damage response (DDR) signaling, benchmarking to wild-type MMR proteins. Our
      results suggest that the MMR gene-specific classifiers do not always align with
      the experimental phenotypes related to DDR. Our study highlights the importance
      of complementary experimental and computational assessment to develop future
      predictors for the assessment of VUS.

PMID- 28494186
TI  - Small interference ITGA6 gene targeting in the human thymic epithelium
      differentially regulates the expression of immunological synapse-related genes.
AB  - The thymus supports differentiation of T cell precursors. This process requires
      relocation of developing thymocytes throughout multiple microenvironments of the
      organ, mainly with thymic epithelial cells (TEC), which control intrathymic T
      cell differentiation influencing the formation and maintenance of the
      immunological synapse. In addition to the proteins of the major
      histocompatibility complex (MHC), this structure is supported by several adhesion
      molecules. During the process of thymopoiesis, we previously showed that laminin
      mediated interactions are involved in the entrance of T-cell precursors into the
      thymus, as well as migration of differentiating thymocytes within the organ.
      Using small interference RNA strategy, we knocked-down the ITGA6 gene (which
      encodes the CD49f integrin alpha-chain) in cultured human TEC, generating a
      decrease in the expression of the corresponding CD49f subunit, in addition to
      modulation in several other genes related to cell adhesion and migration.
      Thymocyte adhesion to TEC was significantly impaired, comprising both immature
      and mature thymocyte subsets. Moreover, we found a modulation of the MHC, with a
      decrease in membrane expression of HLA-ABC, in contrast with increase in the
      expression of HLA-DR. Interestingly, the knockdown of the B2M gene (encoding the
      beta-2 microglobulin of the HLA-ABC complex) increased CD49f expression levels,
      thus unraveling the existence of a cross-talk event in the reciprocal control of
      CD49f and HLA-ABC. Our data suggest that the expression levels of CD49f may be
      relevant in the general control of MHC expression by TEC and consequently the
      corresponding synapse with developing thymocytes mediated by the T-cell receptor.

PMID- 28494187
TI  - The screening of the functional microRNA binding site SNPs in sporadic colorectal
      cancer genes.
AB  - Sporadic colorectal cancer (sCRC) is one of the most commonly diagnosed cancers
      worldwide, but few genetic markers have been identified and used for its early
      detection. MicroRNAs are diverse cellular regulators in cancer pathogenesis that
      bind to the 3'-untranslated region (3'-UTR) of their target mRNAs, and variants
      within the miRNA target sites on sCRC-related genes may influence its
      pathogenesis. To investigate this possibility, we used a bioinformatical method
      to screen SNPs for putative changes in miRNA recognition sites within the 3'-UTR
      of sCRC-related genes. The rs11466537 single nucleotide polymorphism was
      predicted to modify the regulation of hsa-miR-1193 on the Transforming Growth
      Factor beta Receptor II (TGFBR2) gene. Additionally, luciferase reporter assays
      indicated that hsa-miR-1193 bound the T allele more strongly than the A allele of
      rs11466537 (with A being the less frequent variant), and real time-polymerase
      chain reaction and western blot analysis showed that TGFBR2 is significantly
      repressed by hsa-miR-1193. Furthermore, overexpression of hsa-miR-1193 promoted
      HT-29 cell proliferation, while the loss of hsa-miR-1193 inhibited the process.
      Finally, the rs11466537 genotyping result revealed that the frequency of A allele
      carriers was 1.5% in the control blood samples, but 0 in the sCRC patients'
      normal colon tissue samples. Our results demonstrated that hsa-miR-1193 may be
      involved in sCRC tumourigenesis at least in part by suppression of TGFBR2, and
      the A allele of rs11466537 disturbed the regulation of hsa-miR-1193 on TGFBR2.

PMID- 28494188
TI  - Depletion of signal recognition particle 72kDa increases radiosensitivity.
AB  - The identification of genetic determinants that underpin tumor radioresistance
      can help the development of targeted radiosensitizers or aid personalization of
      radiotherapy treatment. Here we identify signal recognition particle 72kDa
      (SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted
      in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24
      (bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony
      formation assays. SRP72 depletion also resulted in the radiosensitization of
      normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect
      is not restricted to tumor cells. Increased radiosensitivity was not due to
      impaired DNA damage signaling or repair as assessed by gamma-H2AX foci formation.
      Instead SRP72 depletion was associated with elevated levels of apoptosis after
      irradiation, as measured by caspase 3/7 activity, PARP-cleavage and Annexin-V
      staining, and with an induction of the unfolded protein response. Together, our
      results show that SRP72 is a novel gene involved in radioresistance.

PMID- 28494189
TI  - Increased placental sFlt-1 but unchanged PlGF expression in late-onset
      preeclampsia.
AB  - OBJECTIVE: To investigate whether differences between late-onset preeclampsia
      (PE) and intrauterine growth restriction (IUGR) can be explained by differential
      placental expression patters of sFlt-1, Flt-1, and placental growth factor
      (PlGF). METHODS: Placental tissues and maternal blood samples from seven patients
      with PE, five IUGR, and seven age-matched controls were studied for mRNA and
      protein levels as well as protein localization and expression intensity. RESULTS:
      Placental PlGF mRNA and protein expression were not altered by placental
      dysfunction while placental villous trophoblast expression intensity of PlGF was
      increased. CONCLUSION: High sFlt-1 concentrations may account for diminished
      maternal serum PlGF levels.

PMID- 28494190
TI  - Formate-nitrite transporters: Monoacids ride the dielectric slide.

PMID- 28494191
TI  - Biomarker for early renal microvascular and diabetic kidney diseases.
AB  - Recognition of early stage of diabetic kidney disease, under common practice
      using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL
      and accepted definition of diabetic kidney disease associated with creatinine
      clearance value below 60 mL/min/1.73 m2, is unlikely. This would lead to delay
      treatment associated with therapeutic resistance to vasodilator due to a
      defective vascular homoeostasis. Other alternative biomarkers related to the
      state of microalbuminuria is not sensitive to screen for early diabetic kidney
      disease (stages I, II). In this regard, a better diagnostic markers to serve for
      this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg),
      cystatin C. Recently, renal microvascular disease and renal ischemia have been
      demonstrated to correlate indirectly with the development of diabetic kidney
      disease and its function. Among these are angiogenic and anti-angiogenic factors,
      namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to
      therapeutic prevention, implementation of treatment at early stage of diabetic
      and nondiabetic kidney disease is able to restore renal perfusion and function.

PMID- 28494192
TI  - Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in
      haemodialysis patients, two-year follow-up.
AB  - Oxidative stress and inflammation are highly intertwined pathophysiological
      processes. We analyzed the markers of these processes and high-sensitive troponin
      I (hsTnI) for mortality prediction in patients on haemodialysis. This study
      enrolled a total of 62 patients on regular haemodialysis. The patients were
      monitored for two years, and the observed outcomes were all-cause and
      cardiovascular mortality. Blood samples were taken before one dialysis session
      for analysis of the baseline concentrations of prooxidant-antioxidant balance
      (PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP
      and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%.
      By univariate and multivariate logistic regression, our findings suggest that
      good predictors of all-cause mortality include hsCRP and PAB (p < .05) and of CVD
      mortality hsCRP (p < .05) and hsTnI (p < .001). To evaluate the relationship
      between the combined parameter measurements and all-cause/CVD mortality risk,
      patients were divided into three groups according to their PAB, hsCRP and hsTnI
      concentrations. The cutoffs for hsCRP and hsTnI and the median for PAB were used.
      Kaplan-Meier survival curves pointed out that the highest mortality risk of all
      cause mortality was in the group with hsCRP levels above the cutoff and PAB
      levels above the median (p < .001). The highest risk of CVD mortality was found
      in the group with hsCRP and hsTnI levels above the cutoff levels (p = .001). Our
      data suggest that hsCRP and PAB are very good predictors of all-cause mortality.
      For CVD complications and mortality prediction in HD patients, the most sensitive
      parameters appear to be hsTnI and hsCRP.

PMID- 28494194
TI  - 17beta-Estradiol mineralization under field and laboratory incubations.
AB  - Mineralization studies of natural steroid hormones (e.g., 17beta-estradiol, E2)
      are performed in environmental incubators, usually under a constant temperature
      such as 20 degrees C. In this paper, we present a microcosm protocol that
      quantified the mineralization of E2 in soils under field temperatures. The nine
      agricultural soils tested had a wide range of soil organic carbon (1.1 to 5.2%)
      and clay (9 to 57%) contents. The calculated time over which half of the applied
      E2 was mineralized (E2-1/2) ranged from 299 to 910 d, and total E2 mineralization
      at 48 d (E2-TOT48) ranged from 4 to 13%. In subsequent laboratory incubations,
      the same soils were incubated under a constant temperature of 20 degrees C, as
      well as under cyclic temperatures of 14.5 degrees C (14 h) and 11.5 degrees C
      (10h), which was within the temperature extremes observed in the field
      microcosms. E2-1/2 ranged from 157 to 686 d at 20 degrees C and from 103 to 608 d
      at the cyclic temperatures, with the E2-TOT48 ranging from 6 to 21% at 20 degrees
      C and from 7 to 30% under cyclic temperatures. Despite the overall 6.75 degrees C
      lower mean temperatures under the cyclic versus constant temperatures, E2
      mineralization was stimulated by the temperature cycles in three soils.
      Regardless of the incubation, the same loamy sand soil always showed larger E2
      mineralization than the other eight soils and this loamy sand soil also had the
      smallest E2 sorption. Current modeling approaches do not take into consideration
      the effects of temperature fluctuations in the field because the input parameters
      used to describe degradation are derived from laboratory incubations at a
      constant temperature. Across the eight soils, E2-1/2 was on average 1.7 times
      larger and E2-TOT48 was on average 0.8 times smaller under field temperatures
      than under a constant 20 degrees C. Hence, we conclude that incubations at 20
      degrees C give a reasonable representation of E2 mineralization occurring under
      field conditions to be expected in a typical Prairie summer season.

PMID- 28494193
TI  - Long-term trends in invasive pneumococcal disease in Manitoba, Canada.
AB  - Invasive pneumococcal disease (IPD) remains a significant public health problem
      in Manitoba, Canada although publically-funded pneumococcal conjugate (PCV7 and
      PCV13) and polysaccharide (PPV23) vaccination programs exist. We analyzed routine
      surveillance and administrative health data to examine trends in IPD rates as
      these vaccines were introduced. Data on all individuals with a laboratory
      confirmed diagnosis of IPD between 2001 and 2014 were obtained from the
      provincial Communicable Diseases Surveillance database and linked with Manitoba's
      provincial immunization registry and physician and hospital databases. We
      calculated IPD incidence rates overall, by serotype and for different population
      subgroups defined by socio-demographic and clinical (e.g., chronic diseases,
      immune status) characteristics. Annual IPD incidence (95%CI) was 8.6 (8.2
      9.1)/100,000 people during the study period (n = 1092), and rates were higher in
      recent years and in regions with predominately indigenous populations. Reduction
      in the incidence of serotypes included in PCV7 have been offset by rising rates
      of PCV13-only serotypes in children, and more recently by rising rates of PPV
      only serotypes and non-vaccine serotypes among young children and older adults
      (>= 65 years). Rates were 3 times higher in those with a chronic disease and
      highest (> 175-fold) among alcoholics, organ-transplant, and chronic kidney
      failure patients. The case fatality rate was 12.0% within 30 d of diagnosis.
      Despite the introduction of several vaccination programs, overall rates of IPD
      have not declined in Manitoba in the last decade, due to increase in incidence of
      non-PCV7 serotypes. A disproportionately high burden of disease impacts
      indigenous communities and people with chronic disease.

PMID- 28494195
TI  - Functionally inactivated dominant viral antigens of human cytomegalovirus
      delivered in replication incompetent adenovirus type 6 vectors as vaccine
      candidates.
AB  - T cell immunity is critical in controlling human cytomegalovirus (HCMV) infection
      in transplant recipients, and T cells targeting viral immediate early proteins
      such as IE1, IE2 and pp65 have been speculated to be more effective against
      reactivation. Here we report efforts to construct replication incompetent
      adenovirus 6 vectors expressing these viral antigens as vaccine candidates. To
      reduce the potential liabilities of these viral proteins as vaccine antigens, we
      introduced mutations to inactivate their reported functions including their
      nuclear localization signals. The modifications greatly reduced their
      localization to the nuclei, thus limiting their interactions with cellular
      proteins important for cell cycle modulation and transactivation. The
      immunogenicity of modified pp65, IE1 and IE2 vaccines was comparable to their
      wild-type counterparts in mice and the immunogenicity of the modified antigens
      was demonstrated in non-human primates.

PMID- 28494197
TI  - Learning Disabilities and Emotional Intelligence.
AB  - The literature is conflicted around the subject of the emotional abilities of
      individuals with Specific Learning Disabilities (SLDs): While many claim
      cognitive challenges are associated with emotional difficulties, some suggest
      emotional and interpersonal abilities are not compromised in such disorders and
      may help individuals compensate and cope effectively with the challenges they
      meet in learning environments. Two studies explored differences in emotional
      intelligence (EI) between young adults with and without SLD. Two samples (matched
      on gender, approximate age, and program of study; n = 100, and unmatched; n =
      584) of college students took self-report and performance-based tests of EI
      (Ability-EI) as well as a measure of self-esteem and demographics associated with
      college performance (e.g.: SAT scores, gender, etc.). The results showed that
      while SAT scores and ability emotional intelligence (Ability-EI) were associated
      with college GPA, Ability-EI did not differ between the two groups, while self
      report measures of EI and self-esteem did show differences, with the group with
      learning disabilities ranking lower. The effects remained stable when we
      controlled for demographics and potential intervening factors. The results
      suggest that EI may play a protective role in the association between background
      variables and college attainment in students with SLD. The results may provide a
      basis for interventions to empower students with SLD in academia.

PMID- 28494196
TI  - Misremembering Past Affect Predicts Adolescents' Future Affective Experience
      During Exercise.
AB  - PURPOSE: Increasing physical activity among adolescents is a public health
      priority. Because people are motivated to engage in activities that make them
      feel good, this study examined predictors of adolescents' feelings during
      exercise. METHOD: During the 1st semester of the school year, we assessed 6th
      grade students' (N = 136) cognitive appraisals of the importance of exercise.
      Participants also reported their affect during a cardiovascular fitness test and
      recalled their affect during the fitness test later that semester. During the 2nd
      semester, the same participants rated their affect during a moderate-intensity
      exercise task. RESULTS: Affect reported during the moderate-intensity exercise
      task was predicted by cognitive appraisals of the importance of exercise and by
      misremembering affect during the fitness test as more positive than it actually
      was. This memory bias mediated the association between appraising exercise as
      important and experiencing a positive change in affect during the moderate
      intensity exercise task. CONCLUSION: These findings highlight the roles of both
      cognitive appraisals and memory as factors that may influence affect during
      exercise. Future work should explore whether affect during exercise can be
      modified by targeting appraisals and memories related to exercise experiences.

PMID- 28494198
TI  - MicroRNA-338 modulates cortical neuronal placement and polarity.
AB  - The precise spatial and temporal regulation of gene expression orchestrates the
      many intricate processes during brain development. In the present study we
      examined the role of the brain-enriched microRNA-338 (miR-338) during mouse
      cortical development. Reduction of miR-338 levels in the developing mouse cortex,
      using a sequence-specific miR-sponge, resulted in a loss of neuronal polarity in
      the cortical plate and significantly reduced the number of neurons within this
      cortical layer. Conversely, miR-338 overexpression in developing mouse cortex
      increased the number of neurons, which exhibited a multipolar morphology. All
      together, our results raise the possibility for a direct role for this non-coding
      RNA, which was recently associated with schizophrenia, in the regulation of
      cortical neuronal polarity and layer placement.

PMID- 28494199
TI  - Fine particulate matter (PM2.5) enhances allergic sensitization in BALB/c mice.
AB  - Ambient particulate matter (PM), a component of air pollution, exacerbates airway
      inflammation and hyperreactivity in asthmatic patients. Studies showed that PM
      possesses adjuvant-like properties that enhance the allergic inflammatory
      response; however, the mechanism (or mechanisms) by which PM enhances the
      allergic response remains to be determined. The aim of this study was to assess
      how exposure to fine PM collected from Sacramento, CA, shapes the allergic airway
      immune response in BALB/c mice undergoing sensitization and challenge with
      ovalbumin (OVA). Eight-week-old BALB/c male mice were sensitized/challenged with
      phosphate-buffered saline (PBS/PBS; n = 6), PM/PBS (n = 6), OVA/OVA (n = 6), or
      OVA + PM/OVA (n = 6). Lung tissue, bronchoalveolar lavage fluid (BALF), and
      plasma were analyzed for cellular inflammation, cytokines, immunoglobulin E, and
      heme oxygenase-1 (HO-1) expression. Mice in the OVA + PM/OVA group displayed
      significantly increased airway inflammation compared to OVA/OVA animals. Total
      cells, macrophages, and eosinophils recovered in BALF were significantly elevated
      in the OVA + PM/OVA compared to OVA/OVA group. Histopathological grading
      indicated that OVA + PM/OVA treatment induced significant inflammation compared
      to OVA/OVA. Both immunoglobulin (Ig) E and tumor necrosis factor (TNF) alpha
      levels were significantly increased in OVA/OVA and OVA + PM /OVA groups compared
      to PBS/PBS control. The number of HO-1 positive alveolar macrophages was
      significantly elevated in lungs of mice treated with OVA + PM /OVA compared to
      OVA/OVA. Our findings suggest that fine PM enhances allergic inflammatory
      response in pulmonary tissue through mechanisms involving increased oxidative
      stress.

PMID- 28494200
TI  - A new therapeutic potential for cancers: One CAR with 2 different engines!
AB  - Tumor cells escape from immune recognition by several mechanisms such as down
      regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose
      of cancer immunotherapy is to robust or reconstruct the capacity of the immune
      system to recognize and kill tumor cells by overwhelming the mechanisms by which
      tumors escape the immune response. One of the novel immunotherapeutic strategies
      were used to potentiate NK- and T cell functions is chimeric antigen receptor
      (CAR). CARs are composed of an antigen-binding domain of a molecule such as an
      antibody (that binds to a tumor associated antigens expressed on the surface of
      tumor cells) and an intracellular T cell activation domain. The CARs provide the
      recognition of target antigen in a MHC-independent manner. CAR-armed T cells may
      be unable to kill their targets in the absence of co-stimulators like NK cells.
      On the other hand, CAR-armed NK cells may also be unable to destroy their targets
      without receiving help signals from Th cells. Thus, if CAR-armed NK cells use
      together with CAR-armed T cells, NK cells will be aggregated to the tumor site.
      Thus, not only CAR T cells will obtain the necessary cytokines/costimulators from
      NK cells, but also other tumor specific T cells will be primed by recognition of
      tumor specific antigen (TSA) associated with MHC class I. These new specific
      primed T cells probably combat against tumor cells which have lost their TAAs
      that CAR-T cells are redirected to them.

PMID- 28494201
TI  - Exploring sexual behaviors and health communication among older women.
AB  - Older women around the globe are generally depicted as asexual beings, which may
      impact patient-provider discussions about sex. We examined data on 703 aging
      women in the United States to compare factors associated with women perceiving
      sex as important and women discussing sex with their physicians since turning 50.
      While 65.1% of participants perceived sex to be important, only 23.8% discussed
      sex with their providers since turning 50. Factors related to discussing sex
      included age, education, having a chronic condition, and consuming alcohol.
      Provider training and tools about sexual health communication could help launch
      those discussions about sex and increase advocacy for older women's sexual
      health.

PMID- 28494202
TI  - Abscisic acid signaling is involved in regulating the mitogen-activated protein
      kinase cascade module, AIK1-MKK5-MPK6.
AB  - Abscisic acid (ABA) plays roles in plant growth and development and in stress
      responses. Recently, we found that ABA regulates ABA-insensitive protein kinase 1
      (AIK1), a mitogen-activated protein kinase kinase kinase. Compared with wild
      type, aik1-1 showed downregulation of ABA-responsive genes (RD29A, MYC2, ABI3 and
      ABI4). Under ABA treatment, the transcript level of KRP1 (Kip-related protein, a
      cyclin-dependent kinase inhibitor) was lower in aik1-1 than in wild-type. The
      activity of ABA-activated MPK6 was decreased in abi1 abi2, and abi1 abi2 hab1,
      and increased in snrk2.2 snrk2.3 and pyr1 pyl1 pyl2 pyl4 mutants. These results
      indicated that AIK1-MKK5-MPK6 functions in ABA responses and requires ABA
      responsive gene expression to regulate ABA-inhibited root growth and cell
      division. The ABA signaling pathway regulates this MAPK cascade.

PMID- 28494203
TI  - Carbofuran degraded by iron-doped anatase: Weakening the cholinesterase
      inhibitory activity in the photoproducts mixture.
AB  - Carbofuran is a toxic carbamate pesticide, and its use has increased in recent
      years. While marketing information indicates stability in different chemical
      media, carbofuran exhibits relative photolability. The aim of this research was
      to decompose carbofuran and to identify the photoproducts achieved when two
      different doped titania photocatalysts were employed under UV irradiation. The
      iron-doped TiO2 materials were obtained (a) via a hydrothermal method and (b) by
      an ultrasound-assisted sol-gel method. The precursors were TiOSO4?xH2O and
      Fe3(NO3).9H2O. X-ray studies confirmed that the anatase phase of the iron-doped
      TiO2 resulted from the two preparation methods. The photocatalytic performance of
      the prepared materials was monitored by LC/ESI-QTOF-MS, enabling the
      identification of photoproducts: oxo-carbamates, hydroxylated benzofuranes, a
      carboxamide, and one amine. By using the iron-doped TiO2 materials, 2,2-dimethyl
      2,3-dihydrobenzofuran-3,7-diol was the most abundant photoproduct, and N,2,2
      trimethyl-2,3-dihydrobenzofuran-7-amine was the only compound that had not been
      previously reported in the photolysis and photocatalysis of carbofuran. The
      product 3-hydroxy carbofuran, a cholinesterase inhibitor, was quantified and was
      found to be transformed into compounds that lack this inhibitive property.

PMID- 28494204
TI  - Bio- and toxic elements in mushrooms from the city of Umea and outskirts, Sweden.
AB  - Edible mushrooms (Albatrellus ovinus, Boletus edulis, Clitocybe odora, Gomphidius
      glutinosus, Leccinum scabrum, Leccinum versipelle, Lycoperdon perlatum, Suillus
      bovinus, Suillus luteus, and Xerocomus subtomentosus) collected from unpolluted
      areas of the city of Umea and its outskirts in the northern part of Sweden were
      examined for contents of toxic metallic elements (Cd, Pb, and Ag) and essential
      macro- and microelements (K, Na, Ca, Mg, Cu, Fe, Mn, and Zn) using a validated
      method and a final measurement by flame atomic absorption spectroscopy (F-AAS).
      The median values of the toxic metallic element concentrations (in mg kg-1 dry
      biomass, db) ranged from: 0.12-3.9, 0.46-5.1, and 0.91-6.2 for Ag, Cd and Pb,
      respectively. For the essential metallic elements, the median values of
      concentrations ranged from: 24000-58000, 15-2000, 59-610, 520-1900, 2.0-97, 16
      150, 15-120, and 4.3-26 mg kg-1 db for K, Na, Ca, Mg, Cu, Zn, Fe, and Mn,
      respectively. The baseline concentrations of the metallic elements determined in
      mushrooms were mainly affected by the fungal species. The assessed probable
      maximal dietary intake of Cd (0.002 mg kg-1 body mass) solely from a mushroom
      meal was only slightly below a revised value of the tolerable weekly intake for
      this element, while for Pb (0.003 mg kg-1 body mass) it was tenfold below the
      provisionally tolerable weekly intake.

PMID- 28494205
TI  - What determines supportive behaviors following bereavement? A systematic review
      and call to action.
AB  - Very few factors that impact the grieving process can be modified after the fact
      to the extent that social support can. However, social support has received
      limited research attention, resulting in little conceptual understanding of the
      mechanisms behind perceptions of, and intentions to support, grieving persons.
      This systematic review aimed to explore bereaved, decedent, and respondent
      related determinants of the provision of social support. The review yielded 42
      studies impacted by various methodological and sampling limitations. This review
      poses a call to the field for more rigorous study of social support determinants
      to better assist the bereaved and their natural supporters.

PMID- 28494206
TI  - Component-resolved evaluation of the content of major allergens in therapeutic
      extracts for specific immunotherapy of honeybee venom allergy.
AB  - Allergen-specific immunotherapy is the only curative treatment of honeybee venom
      (HBV) allergy, which is able to protect against further anaphylactic sting
      reactions. Recent analyses on a molecular level have demonstrated that HBV
      represents a complex allergen source that contains more relevant major allergens
      than formerly anticipated. Moreover, allergic patients show very diverse
      sensitization profiles with the different allergens. HBV-specific immunotherapy
      is conducted with HBV extracts which are derived from pure venom. The allergen
      content of these therapeutic extracts might differ due to natural variations of
      the source material or different down-stream processing strategies of the
      manufacturers. Since variations of the allergen content of therapeutic HBV
      extracts might be associated with therapeutic failure, we adressed the component
      resolved allergen composition of different therapeutic grade HBV extracts which
      are approved for immunotherapy in numerous countries. The extracts were analyzed
      for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and
      Api m 10. Using allergen-specific antibodies we were able to demonstrate the
      underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api
      m 10 in particular therapeutic extracts. Taken together, standardization of
      therapeutic extracts by determination of the total allergenic potency might imply
      the intrinsic pitfall of losing information about particular major allergens.
      Moreover, the variable allergen composition of different therapeutic HBV extracts
      might have an impact on therapy outcome and the clinical management of HBV
      allergic patients with specific IgE to particular allergens.

PMID- 28494207
TI  - Psychological Vulnerability and Gambling in Later Life.
AB  - OBJECTIVES: Because behavioral problems often emerge from maladaptive coping
      methods, we investigated whether unmet basic psychological needs evolve toward a
      level of psychological vulnerability that puts older adults who gamble at risk
      for becoming problem gamblers. METHODS: Data from a community sample of 379
      adults ages 60 and above were analyzed using structural equation modeling.
      Participants responded to items regarding their demographics, gambling frequency,
      engagement in at-risk gambling behaviors, and the extent to which their basic
      psychological needs were met. RESULTS: Satisfaction of basic psychological needs
      among older adults who gamble was negatively associated with their being at risk
      for developing a gambling problem. Satisfaction of basic psychological needs also
      mediated the negative effect of socioeconomic status on at-risk gambling
      behavior. CONCLUSION: Social workers should become mindful of how older adults,
      who are confronting psychological vulnerabilities in later life, might well turn
      to gambling as a maladaptive coping mechanism.As per journal style, abstract must
      not exceed100 words. Please amend accordingly.

PMID- 28494208
TI  - Silicon nanowires enhanced proliferation and neuronal differentiation of neural
      stem cell with vertically surface microenvironment.
AB  - Owing to its biocompatibility, noncytotoxicity, biodegradability and three
      dimensional structure, vertically silicon nanowires (SiNWs) arrays are a
      promising scaffold material for tissue engineering, regenerative medicine and
      relevant medical applications. Recently, its osteogenic differentiation effects,
      reorganization of cytoskeleton and regulation of the fate on stem cells have been
      demonstrated. However, it still remains unknown whether SiNWs arrays could affect
      the proliferation and neuronal differentiation of neural stem cells (NSCs) or
      not. In the present study, we have employed vertically aligned SiNWs arrays as
      culture systems for NSCs and proved that the scaffold material could promote the
      proliferation and neuronal differentiation of NSCs while maintaining excellent
      cell viability and stemness. Immunofluorescence imaging analysis, Western blot
      and RT-PCR results reveal that NSCs proliferation and neuronal differentiation
      efficiency on SiNWs arrays are significant greater than that on silicon wafers.
      These results implicate SiNWs arrays could offer a powerful platform for NSCs
      research and NSCs-based therapy in the field of neural tissue engineering.

PMID- 28494210
TI  - Tobacco-Free Policy Compliance Behaviors among College Students: A Theory of
      Planned Behavior Perspective.
AB  - The purpose of this study was to examine the theory of planned behavior (TPB) as
      a framework for understanding tobacco-free policy compliance behaviors.
      Undergraduate student smokers (n = 479) on a college campus with a tobacco-free
      policy were randomly selected to report their tobacco-free compliance behaviors
      and respond to TPB items. A path analysis found all constructs of the TPB model
      to be significantly related to tobacco-free policy compliance behaviors. The
      results obtained from this study fill gaps in the mostly atheoretical literature
      regarding our understanding of tobacco-free policy compliance behaviors as well
      as extend our knowledge of the TPB. Implications for this study provide
      recommendations for universities, health organizations, and government agencies
      currently attempting to enforce compliance with a tobacco-free policy.

PMID- 28494209
TI  - Antibiotic resistance, virulence factors and biofilm formation ability in
      Escherichia coli strains isolated from chicken meat and wildlife in the Czech
      Republic.
AB  - Attachment of pathogenic bacteria to food contact surfaces and the subsequent
      biofilm formation represent a serious threat for the food industry, since these
      bacteria are more resistant to antimicrobials or possess more virulence factors.
      The main aim of this study was to investigate the correlation between antibiotic
      resistance against 13 antibiotics, distribution of 10 virulence factors and
      biofilm formation in 105 Escherichia coli strains according to their origin. The
      high prevalence of antibiotic resistance that we have found in wildlife isolates
      could be acquired by horizontal transfer of resistance genes from human or
      domestic or farm animals. Consequently, these commensal bacteria might serve as
      indicator of antimicrobial usage for human and veterinary purposes in the Czech
      Republic. Further, 46 out of 66 resistant isolates (70%) were able to form
      biofilm and we found out statistically significant correlation between prevalence
      of antibiotic resistance and biofilm formation ability. The highest prevalence of
      antibiotic resistance was observed in weak biofilm producers. Biofilm formation
      was not statistically associated with any virulence determinant. However, we
      confirmed the correlation between prevalence of virulence factors and host
      origin. Chicken isolates possessed more virulence factors (66%), than isolates
      from wildlife (37%). We can conclude that the potential spread of antibiotic
      resistance pattern via the food chain is of high concern for public health. Even
      more, alarming is that E. coli isolates remain pathogenic potential with ability
      to form biofilm and these bacteria may persist during food processing and
      consequently lead to greater risks of food contamination.

PMID- 28494211
TI  - Pecoramyces ruminantium, gen. nov., sp. nov., an anaerobic gut fungus from the
      feces of cattle and sheep.
AB  - The anaerobic gut fungi (AGF) inhabit the rumen and alimentary tracts of multiple
      ruminant and nonruminant herbivores, belong to a distinct phylum-level lineage
      (Neocallimastigomycota), and play an important role in plant biomass degradation
      in many herbivores. As part of a wider effort to obtain AGF with high
      lignocellulolytic capacities, we isolated and characterized four different AGF
      strains from the feces of cattle and sheep. Microscopically, isolates produced
      monocentric thalli and monoflagellated zoospores. Phylogenetic analysis revealed
      that all isolates formed a monophyletic cluster with strong bootstrap support as
      a sister clade to the genus Orpinomyces and close to Neocallimastix, an
      unexpected result because these two genera of AGF form polyflagellated zoospores.
      Isolates displayed a smooth biofilm-like growth in liquid medium and formed small
      (0.5-1 mm) pinpoint circular colonies on agar roll tubes. Both endogenous and
      exogenous sporangia were observed with variable shapes and sizes. Zoospores were
      mainly spherical, with diameters ranging between 3.8 and 12.5 um, and mostly a
      single flagellum. All strains exhibited similar substrate utilization patterns
      and comparable cellulolytic and xylanolytic activities. Similar ITS1 sequences
      falling within the same distinctive clade were found on GenBank, with all
      environmental samples obtained from diverse ruminant and pseudoruminant hosts
      from three continents, but not from any hindgut-fermenting hosts. Given the high
      level of sequence divergence between our strains and closest cultured
      representatives and their distinct microscopic/macroscopic features, we propose a
      new genus, Pecoramyces, from the name of the taxonomic infraorder Pecora ("horned
      ruminants" or "higher ruminants"; derived from the Latin word for horned
      livestock), and a new species, P. ruminantium (since occurrence seems to be
      specific to ruminant/pseudoruminant foregut, but not hindgut-fermenting mammals).

PMID- 28494212
TI  - Retinal Toxicity of Acai Fruit (Euterpe Oleracea) Dye Concentrations in Rabbits:
      Basic Principles of a New Dye for Chromovitrectomy in Humans.
AB  - PURPOSE: Evaluate toxicity of acai fruit (Euterpe oleracea) dye concentrations in
      a rabbit model. METHODS: Rabbits were injected intravitreously with 10%, 25%, and
      35% acai dye concentrations. Control eyes received balanced salt solution (BSS).
      Electroretinogram (ERG), fundus imaging, fluorescein angiography (FA), optical
      coherence tomography (OCT), and light and transmission electron microscopy
      (LM/TEM) were performed. RESULTS: Fundus imaging showed increased vitreous
      opacity with increased dye concentrations. FA and OCT showed normality with all
      concentrations. Comparisons between BSS and dye concentrations were analyzed
      using Kruskal-Wallis and Mood's median test (p < 0.05). At 24 h, ERGs showed
      reduced amplitudes from baseline in all eyes. Median b-wave amplitudes
      nonsignificantly decreased and latency increased with 10% and 25%; findings were
      significant (p < 0.05) for 35%. LM and TEM showed no abnormalities for 10% and
      25%. With 35%, TEM showed ganglion cell edema at 24 h that resolved after 7 days.
      Vacuolization, multilamellar bodies, and nerve bundle damage occurred at 24 h/7
      days in the inner nuclear layer. Mitochondrial cristae disruption occurred in the
      inner photoreceptor segment at 24 h that decreased by 7 days. CONCLUSION: Ten and
      twenty-five percent concentrations were safe and may improve identification of
      the posterior hyaloid and internal limiting membrane during chromovitrectomy in
      humans.

PMID- 28494213
TI  - Tumor-like microenvironment in oral lichen planus: evidence of malignant
      transformation?
AB  - INTRODUCTION: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory
      autoimmune disease affecting 0.1% to 4% of the world population. The WHO has
      already recognized it as an oral potentially malignant disorder. However, the
      reasons for the malignant transformation of OLP are far from being elucidated
      clearly. The purpose of this review is to clarify how the tumor-like
      microenvironment in OLP mediates its potentially malignant transformation. Areas
      covered: We review published articles on the microenvironment characteristics of
      tumors, the pathogenesis of OLP, and clinical studies of OLP. The main sources of
      literature derive from MEDLINE/Pubmed and Thomson Reuter's Web of Science. Expert
      commentary: The tumor-like microenvironment, including hypoxic, inflammatory,
      immune and acid microenvironment, greatly contributes to carcinogenesis of OLP
      patients. In order to effectively monitor the malignant transformation of OLP,
      future studies should focus on long-term follow-up and select important detection
      biomarkers.

PMID- 28494214
TI  - The role and therapeutic targeting of IL-6 in rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune chronic disease with
      joint and systemic inflammation and it has been found that interleukin-6 (IL-6)
      plays a key role in RA. Indeed, various clinical studies have proved that the
      first-in-class IL-6 inhibitor, tocilizumab, a humanized anti-IL-6 receptor
      monoclonal antibody, showed outstanding efficacy in RA. Areas covered: We review
      here the role of IL-6 in the inflammatory conditions and how IL-6 contributes to
      pathogenesis of RA, what induces IL-6 and how IL-6 expression is regulated.
      Furthermore, clinical studies of tocilizumab for RA are summarized, Expert
      commentary: We review and discuss the prospects for future applications of IL-6
      targeting therapy and new therapeutic strategies targeting IL-6. Finally, we
      discuss relevant issues with regard to the clinical management of IL-6 blockade
      in RA.

PMID- 28494215
TI  - Potential ultrastructure predicting factors for hepatocellular carcinoma in HCV
      infected patients.
AB  - Hepatitis C virus represents one of the rising causes of hepatocellular carcinoma
      (HCC). Although the early diagnosis of HCC is vital for successful curative
      treatment, the majority of lesions are diagnosed in an irredeemable phase. This
      work deals with a comparative ultrastructural study of experimentally gradually
      induced HCC, surgically resected HCC, and potential premalignant lesions from HCV
      infected patients, with the prospect to detect cellular criteria denoting
      premalignant transformation. Among the main detected pathological changes which
      are postulated to precede frank HCC: failure of normal hepatocyte regeneration
      with star shape clonal fragmentation, frequent elucidation of hepatic progenitor
      cells and Hering canals, hepatocytes of different electron density loaded with
      small sized rounded monotonous mitochondria, increase junctional complexes
      bordering bile canaliculi and in between hepatocyte membranes, abundant cellular
      proteinaceous material with hypertrophied or vesiculated rough endoplasmic
      reticulum (RER), sequestrated nucleus with proteinaceous granular material or
      hypertrophied RER, formation of lipolysosomes, large autophagosomes, and micro
      vesicular fat deposition. In conclusion, the present work has visualized new
      hepatocytic division or regenerative process that mimic splitting or clonal
      fragmentation that occurs in primitive creature. Also, new observations that may
      be of value or assist in predicting HCC and identifying the appropriate patient
      for surveillance have been reported. Moreover, it has pointed to the possible
      malignant potentiality of liver stem/progenitor cells. For reliability, the
      results can be subjected to cohort longitudinal study.

PMID- 28494216
TI  - Cough reflex hypersensitivity: A role for neurotrophins.
AB  - Cough is one of the most common complaints for which sufferers seek medical
      assistance. However, currently available drugs are not very effective in treating
      cough, particularly that which follows an upper respiratory tract infection.
      Nonetheless, there has been a significant increase in our understanding of the
      mechanisms and pathways of the defensive cough as well as the
      hypersensitive/pathophysiological cough, both at airway and central nervous
      system (CNS) levels. Numerous molecules and signaling pathways have been
      identified as potential targets for antitussive drugs, including neurotrophins
      (NTs). NTs belong to a family of trophic factors and are critical for the
      development and maintenance of neurons in the central and peripheral nervous
      system including sympathetic efferents, sensory neuron afferents, and immune
      cells. Nerve growth factor (NGF) was the first member of the NT family to be
      discovered, with wide ranging actions associated with synapse formation,
      survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression
      and activity of functionally important proteins such as ion channels, receptors,
      and neurotransmitters. In addition, NGF has been implicated in several disease
      states particularly neuropathic pain and most recently in the sensitization of
      the cough reflex. This review will briefly address the peripheral and central
      sensitization mechanisms of airway neurons and will then focus on NGF signaling
      and its role in cough hypersensitivity.

PMID- 28494217
TI  - Urinary IL-8 is a marker of early and long-term graft function after renal
      transplantation.
AB  - In this study, we examined whether the IL-8 content of urine sampled on day 1 and
      day 14 after renal transplantation is a marker of early and long-term renal
      function. Moreover, we assessed whether its concentration is positively
      correlated with the matrix metalloproteinase-9 (MMP-9) content of urine sampled
      on day 1 and day 30 and 12 months after renal transplantation. Our analysis
      covered 87 patients who underwent a kidney transplant. The patients were observed
      for an average of 30 months (12-60 months). The IL-8 concentration determined on
      day 1 was significantly negatively correlated with creatinine clearance early
      after renal transplantation (on days 1, 7, 14 and 30), as well as during long
      term observations. IL-8 concentration in urine sampled on day 1 and day 14 was
      higher in patients demonstrating DGF than in those without DGF. No relationship
      was found between IL-8 content and cold ischaemia time. MMP-9 activity determined
      on day 1 and month 3 after renal transplantation was positively correlated with
      the IL-8 content determined in urine sampled on day 1, Rs = +0.32, p < .05 and Rs
      = +0.31, p < .05, respectively. The results of this study suggest that a high IL
      8 content in urine sampled on day 1 after renal transplantation is an
      unfavourable marker of early and long-term (years-long) graft function. A high IL
      8 content in urine sampled on day 1 after renal transplantation was positively
      correlated with the activity of metalloproteinase-9 in urine. This proves that
      both of these chemokines cooperate in ischaemia-reperfusion injuries in
      transplanted kidneys.

PMID- 28494218
TI  - Maternal cigarette smoking during pregnancy and offspring DNA methylation in
      midlife.
AB  - Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in
      specific CpG sites (CpGs) in infants and children. We investigated whether MSP,
      independent of own personal active smoking, was associated with midlife DNA
      methylation in CpGs that were previously identified in studies of MSP-DNA
      methylation in children. We used data on MSP collected from pregnant mothers of
      89 adult women born in 1959-1964 and measured DNA methylation in blood
      (granulocytes) collected in 2001-2007 (mean age: 43 years). Seventeen CpGs were
      differentially methylated by MSP, with multiple CpGs mapping to CYP1A1, MYO1G,
      AHRR, and GFI1. These associations were consistent in direction with prior
      studies (e.g., MSP associated with more and less methylation in AHRR and CYP1A1,
      respectively) and, with the exception of AHRR CpGs, were not substantially
      altered by adjustment for active smoking. These preliminary results confirm prior
      prospective reports that MSP influences the offspring DNA methylation, and
      extends the timeframe to midlife, and suggest that these effects may persist into
      adulthood, independently of active smoking.

PMID- 28494219
TI  - Oxidative degradation of tetramethylammonium hydroxide (TMAH) by UV/persulfate
      and associated acute toxicity assessment.
AB  - Tetramethylammonium hydroxide (TMAH) is widely used in high-tech industries as a
      developing agent. Ultraviolet (UV) light-activated persulfate (PS, S2O82-) can be
      used to generate strongly oxidative sulfate radicals, and it also exhibits the
      potential to treat TMAH-containing wastewater. This study initially investigated
      the effect of S2O82- concentration and UV strength on the UV/S2O82- process for
      the degradation of TMAH in a batch reactor. The results suggested that 15 watts
      (W) of UV-activated S2O82- at concentrations of 10 or 50 mM resulted in pseudo
      first-order TMAH degradation rate constants of 3.1-4.2 * 10-2 min-1, which was
      adopted for determining the hydraulic retention time (HRT) in a continuous
      stirred tank reactor (CSTR). The operating conditions (15 W UV/10 mM S2O82-) with
      a HRT of 129 min resulted in stable residual concentrations of S2O82- and TMAH at
      approximately 2.6 mM and 20 mg L-1 in effluent, respectively. Several TMAH
      degradation intermediates including trimethylamine, dimethylamine, and
      methylamine were also detected. The effluent was adjusted to a neutral pH and
      evaluated for its biological acute toxicity using Cyprinus carpio as a bioassay
      organism. The "bio-acute toxicity unit" (TUa) was determined to be 1.41, which
      indicated that the effluent was acceptable for being discharged into an aquatic
      ecosystem.

PMID- 28494220
TI  - Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in
      Piglets.
AB  - Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological
      effects, including antimicrobial and immunomodulatory activities. Recently, it
      was shown that LF also regulates bone cell activity, suggesting its therapeutic
      effect on postmenopausal bone loss. However, a minimal amount is known regarding
      the effects of recombinant human LF (rhLF) supplementation on bone status in
      young healthy infants. We found osteoblast cell differentiation was significantly
      promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF
      rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase
      (p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone
      status in vivo, we used a piglet model, which is a useful model for human
      infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation
      markers, Serum calcium concentration, bone mineral density (BMD), bone mineral
      content (BMC), tibia bone strength, and the overall metabolite profile analysis
      showed that rhLF was advantageous to the bone growth in piglets. These findings
      suggest that rhLF supplementation benefits neonate bone health by modulating bone
      formation.

PMID- 28494221
TI  - Does copy number variation of APOL1 gene affect the susceptibility to focal
      segmental glomerulosclerosis?
AB  - BACKGROUND: APOL1 risk variants (G1 and G2) are associated with increased
      susceptibility to focal segmental glomerulosclerosis (FSGS) in African
      population. However, the two risk mutations were not found in Chinese FSGS
      patients. In this study, we explored the association between the copy number
      variation (CNV) of APOL1 gene and FSGS. METHODS: APOL1 copy number variations
      were detected by quantitative real-time PCR with TaqMan probes and compared
      between 133 FSGS patients and 123 controls. The association between CNV of APOL1
      gene and clinical parameters was also investigated. RESULTS: The distribution of
      APOL1 CNV did not show significant difference between FSGS patients and controls.
      The creatinine and proteinuria in the high copy number group (CN >= 3) were
      higher than the other two groups, but the difference was not significant (p >
      .05). The FSGS pathological types were different among the three groups.
      CONCLUSION: There was no significant difference in the distribution of APOL1 gene
      copy variants between FSGS patients and normal controls, and there was no
      significant correlation between the APOL1 gene CNV and the FSGS patients'
      clinical manifestations. APOL1 CNVs may be not associated with susceptibility to
      FSGS.

PMID- 28494222
TI  - Distribution and incorporation mode of the herbicide MCPA in soil derived organo
      clay complexes.
AB  - The incorporation of xenobiotics into soil, especially via covalent bonds or
      sequestration has a major influence on the environmental behavior including
      toxicity, mobility, and bioavailability. The incorporation mode of 4-chloro-2
      methylphenoxyacetic acid (MCPA) into organo-clay complexes has been investigated
      under a low (8.5 mg MCPA/kg soil) and high (1000 mg MCPA/kg soil) applied
      concentration, during an incubation period of up to 120 days. Emphasis was laid
      on the elucidation of distinct covalent linkages between non-extractable MCPA
      residues and humic sub-fractions (humic acids, fulvic acids, and humin). The
      cleavage of compounds by a sequential chemical degradation procedure (OH-, BBr3,
      RuO4, TMAH thermochemolysis) revealed for both concentration levels ester/amide
      bonds as the predominate incorporation modes followed by ether linkages. A
      possible influence of the soil microbial activity on the mode of incorporation
      could be observed in case of the high level samples. Structure elucidation
      identified MCPA as the only nonextractable substance, whereas the metabolite 4
      chloro-2-methylphenol was additionally found as bioavailable and bioaccessible
      compound.

PMID- 28494223
TI  - Audiovisual integration supports face-name associative memory formation.
AB  - Prior multisensory experience influences how we perceive our environment, and
      hence how memories are encoded for subsequent retrieval. This study investigated
      if audiovisual (AV) integration and associative memory formation rely on
      overlapping or distinct processes. Our functional magnetic resonance imaging
      results demonstrate that the neural mechanisms underlying AV integration and
      associative memory overlap substantially. In particular, activity in anterior
      superior temporal sulcus (STS) is increased during AV integration and also
      determines the success of novel AV face-name association formation. Dynamic
      causal modeling results further demonstrate how the anterior STS interacts with
      the associative memory system to facilitate successful memory formation for AV
      face-name associations. Specifically, the connection of fusiform gyrus to
      anterior STS is enhanced while the reverse connection is reduced when
      participants subsequently remembered both face and name. Collectively, our
      results demonstrate how multisensory associative memories can be formed for
      subsequent retrieval.

PMID- 28494224
TI  - Trauma, Case Studies, and Dual Diagnosis Consequences.

PMID- 28494225
TI  - What about me? The loss of self through the experience of traumatic childbirth.
AB  - BACKGROUND AND OBJECTIVE: birth trauma has become an increasingly recognised
      maternal mental health issue and has important implications for both mother and
      infant. The importance of subjective birth experience in the development of birth
      trauma has been identified and may mediate the lack of theoretical consistency in
      this area. The current study aims to explore the subjective experience of birth
      trauma among first time mothers in Ireland. It aims to separate the potential
      effects of peripartum depression (PPD) from this in limiting this qualitative
      investigation to women who reported birth trauma, without PPD. DESIGN: mixed
      methods: Quantitative methods facilitated the recruitment of participants, the
      selection of a homogenous sample and addressed previous methodological flaws in
      birth trauma research. Interpretative Phenomenological Analysis (IPA) was used to
      explore the subjective experience of traumatic childbirth. PARTICIPANTS: seven,
      first- time mothers who reported a traumatic childbirth, without significant
      symptoms of PPD participated. MEASUREMENT AND FINDINGS: screening measures of
      birth trauma and PPD were completed by participants. A semi-structured interview
      was then conducted with each participant about their childbirth experience.
      Interviews were transcribed and analysed using IPA. The primary superordinate
      theme recounted how the identity and individuality of women is ignored and
      discounted, throughout the process of childbirth. Identity is challenged and
      altered as a result of women's incompatibility with the maternity system.
      CONCLUSIONS: this study supports the existence of birth trauma in an Irish
      context and highlights the subjective experience of women as central to the
      development of birth trauma. IMPLICATIONS FOR PRACTICE: acknowledgement and
      inclusion of the mother as an individual throughout the process of childbirth may
      be protective in limiting the experience of birth trauma.

PMID- 28494226
TI  - The effect of prior experience on children's tool innovation.
AB  - Spontaneous tool innovation to solve physical problems is difficult for young
      children. In three studies, we explored the effect of prior experience with tools
      on tool innovation in children aged 4-7years (N=299). We also gave children an
      experience more consistent with that experienced by corvids in similar studies to
      enable fairer cross-species comparisons. Children who had the opportunity to use
      a premade target tool in the task context during a warm-up phase were
      significantly more likely to innovate a tool to solve the problem on the test
      trial compared with children who had no such warm-up experience. Older children
      benefited from either using or merely seeing a premade target tool prior to a
      test trial requiring innovation. Younger children were helped by using a premade
      target tool. Seeing the tool helped younger children in some conditions. We
      conclude that spontaneous innovation of tools to solve physical problems is
      difficult for children. However, children from 4years of age can innovate the
      means to solve the problem when they have had experience with the solution
      (visual or haptic exploration). Directions for future research are discussed.

PMID- 28494227
TI  - Spontaneous quorum sensing mutation modulates electroactivity of Pseudomonas
      aeruginosa PA14.
AB  - Pseudomonas aeruginosa is able to interact with the anode of a bioelectrochemical
      system through redox active phenazines. Earlier studies showed that this
      interaction is strain and carbon source dependent. With a spontaneously formed
      DeltalasR mutant of P. aeruginosa PA14 and the wildtype, we investigated the
      connection between the complex quorum sensing network and current production.
      Depending on the carbon source, phenazine production and subsequently current
      generation are effected differently in these two populations. In glucose-fed
      cultures, the lack of the LasR regulator led to a shift in phenazine
      concentration, relative composition, and time profiles. In contrast, with the
      common fermentation product 2,3-butanediol as carbon substrate, no phenazine
      production was detected for the DeltalasR mutant. For the wildtype, this carbon
      source is known to induce phenazine synthesis and elevated current production.
      This work supports the earlier hypothesis of a signaling link between 2,3
      butanediol and the quorum-sensing regulatory system and extends this hypothesis
      to predict a lasR-dependent interaction. The wildtype and mutant population were
      also evaluated in direct competition, showing strong initial dominance of the
      wildtype but a higher survival rate of the DeltalasR mutant in later stages of
      growth. We found no evidence for strong social interactions between these two
      subpopulations.

PMID- 28494228
TI  - Enhanced oxygen reducing biocathode electroactivity by using sediment extract as
      inoculum.
AB  - Autotrophic bacteria are able to catalyze cathodic oxygen reduction as a
      renewable and sustainable inexpensive catalyst. However, the performance of
      biocathode varied over reactors, and we still not know how inoculums affect this
      system. Using three different inoculum of wastewater (WW), sediment extract (SE)
      and soil extract (SO) in parallel reactors, we found that SE achieved the
      shortest setup time (17-25% shorter) as well as the highest power density
      compared to those of SO and WW. Cyclic voltammetry (CV) further revealed that the
      current densities of SE biocathodes (100+/-1A/m3) was 150% and 67% higher than
      those of WW biocathodes (40+/-1A/m3) and SO biocathodes (65+/-1A/m3). Community
      analysis showed the selective pressure on biocathode facilitated the growth of
      Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria families. Different
      from WW and SO biocathodes, Nitrospirae was selectively enriched in SE
      biocathodes, corresponding to an obvious increase in Unidentified Nitrospiraceae
      population at genus level, which may play an important role on the cathodic
      electroactivity. These results confirmed that sediment extract is a better
      bacteria source than soil and wastewater for the acclimation of autotrophic
      electroactive bacteria, and the community comparison provided broader knowledge
      on biocathode microbiology.

PMID- 28494229
TI  - An algorithm for quantitatively modeling reflected ultrasonic bounded pulses and
      beams.
AB  - The study of the reflected acoustic waves plays an important role in our
      understanding of media. We provide an algorithm to propagate the ultrasonic
      bounded beam source and study its reflection from any horizontal and homogenous
      water-solid boundary. This algorithm implements a hybrid combination of the phase
      advance wavefield continuation in the frequency domain and the complex analytic
      solution for the acoustic reflectivity. The peak amplitude of the specularly
      reflected beam is in agreement with the laboratory measured acoustic reflection
      from water-Aluminum and water-Copper alloy boundaries. The algorithm is able to
      model the observed critical reflection as well as the null in the reflected
      amplitude at the Rayleigh critical angle from the acoustic wave. This algorithm
      is a crucial tool to understand the full reflected wave from material immersed in
      water in any azimuthal or incidental angles. The software of this algorithm and
      acoustic reflectivity from both solid materials are provided.

PMID- 28494230
TI  - Study on chemical mechanical polishing of silicon wafer with megasonic vibration
      assisted.
AB  - Chemical mechanical polishing (CMP) is the primary method to realize the global
      planarization of silicon wafer. In order to improve this process, a novel method
      which combined megasonic vibration to assist chemical mechanical polishing (MA
      CMP) is developed in this paper. A matching layer structure of polishing head was
      calculated and designed. Silicon wafers are polished by megasonic assisted
      chemical mechanical polishing and traditional chemical mechanical polishing
      respectively, both coarse polishing and precision polishing experiments were
      carried out. With the use of megasonic vibration, the surface roughness values Ra
      reduced from 22.260nm to 17.835nm in coarse polishing, and the material removal
      rate increased by approximately 15-25% for megasonic assisted chemical mechanical
      polishing relative to traditional chemical mechanical polishing. Average Surface
      roughness values Ra reduced from 0.509nm to 0.387nm in precision polishing. The
      results show that megasonic assisted chemical mechanical polishing is a feasible
      method to improve polishing efficiency and surface quality. The material removal
      and finishing mechanisms of megasonic vibration assisted polishing are
      investigated too.

PMID- 28494231
TI  - HIV Latency Gets a New Histone Mark.
AB  - Transcriptional latency of integrated HIV-1 provirus represents a major obstacle
      to curing HIV. In this issue of Cell Host & Microbe, Boehm et al. (2017) identify
      a new lysine methyltransferase that writes a repressive histone mark associated
      with HIV-1 latency. The results are important for strategies to pharmacologically
      reverse HIV-1 latency.

PMID- 28494232
TI  - RAS and ROS-A Story of Pseudomonas Survival.
AB  - Some pathogens block generation of reactive oxygen species to evade neutrophil
      killing, but how that is accomplished is poorly understood. In this issue of Cell
      Host & Microbe, Vareechon et al. (2017) describe ADP-ribosylation of Ras as a
      strategy to inhibit assembly of neutrophil NADPH oxidase.

PMID- 28494233
TI  - Don't Bite the Hand that Feeds You.
AB  - Eukaryotic-bacterial symbioses are ubiquitous in nature. Pathogens and symbionts
      employ similar machinery, yet symbionts can minimize host damage. In this issue
      of Cell Host & Microbe, Enomoto et al. (2017) demonstrate how quorum sensing
      regulates expression of virulence genes at appropriate times, thereby enabling
      symbiont retention throughout the host lifespan.

PMID- 28494234
TI  - An Elegan(t) Screen for Drug-Microbe Interactions.
AB  - Microbes affect drug responses, but mechanisms remain elusive. Two papers in Cell
      exploit C. elegans to infer anticancer drug mechanisms. Through high-throughput
      screens of drug-microbe-host interactions, Garcia-Gonzalez et al. (2017) and
      Scott et al. (2017) determine that bacterial metabolism underpins
      fluoropyrimidine cytotoxicity, providing a paradigm for unraveling bacterial
      mechanisms in drug metabolism.

PMID- 28494235
TI  - ADE-ing and Abetting Zika.
AB  - Although dengue virus (DENV) antibodies can neutralize or enhance Zika virus
      (ZIKV) infection in vitro, their contribution to ZIKV infection in vivo remains
      unclear. In a recent issue of Science, Bardina et al. (2017) explore the
      protective versus pathogenic roles of DENV-immune antibodies in ZIKV infection
      using a mouse model.

PMID- 28494236
TI  - Allied Commensal Forces against Vancomycin-Resistant Enterococci.
AB  - In this issue of Cell Host & Microbe, Caballero et al. (2017) define a precise,
      limited consortium of commensal bacteria that restores resistance to colonization
      by clinically vexing vancomycin-resistant Enterococcus species.

PMID- 28494237
TI  - Microbial Vertical Transmission during Human Pregnancy.
AB  - Congenital infections with pathogens such as Zika virus, Toxoplasma gondii,
      Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster
      virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity
      and mortality worldwide. Despite the devastating impact of microbial infections
      on the developing fetus, relatively little is known about how pathogens
      associated with congenital disease breach the placental barrier to transit
      vertically during human pregnancy. In this Review, we focus on transplacental
      transmission of pathogens during human gestation. We introduce the structure of
      the human placenta and describe the innate mechanisms by which the placenta
      restricts microbial access to the intrauterine compartment. Based on current
      knowledge, we also discuss the potential pathways employed by microorganisms to
      overcome the placental barrier and prospects for the future.

PMID- 28494238
TI  - SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency.
AB  - Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin
      remodeling complexes and post-translational histone modifications likely play key
      roles in HIV-1 reactivation, but the underlying mechanisms are incompletely
      understood. We performed an RNAi-based screen of human lysine methyltransferases
      and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme
      that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological
      inhibition reactivated latent HIV-1 in T cell lines and in primary CD4+ T cells.
      SMYD2 associated with latent HIV-1 promoter chromatin, which was enriched in
      monomethylated lysine 20 at histone H4 (H4K20me1), a mark lost in cells lacking
      SMYD2. Further, we find that lethal 3 malignant brain tumor 1 (L3MBTL1), a reader
      protein with chromatin-compacting properties that recognizes H4K20me1, was
      recruited to the latent HIV-1 promoter in a SMYD2-dependent manner. We propose
      that a SMYD2-H4K20me1-L3MBTL1 axis contributes to HIV-1 latency and can be
      targeted with small-molecule SMYD2 inhibitors.

PMID- 28494239
TI  - CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency
      Factors.
AB  - Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (BL) and
      immunosuppression-related lymphomas. These B cell malignancies arise by distinct
      transformation pathways and have divergent viral and host expression programs. To
      identify host dependency factors resulting from these EBV+, B cell-transformed
      cell states, we performed parallel genome-wide CRISPR/Cas9 loss-of-function
      screens in BL and lymphoblastoid cell lines (LCLs). These highlighted 57 BL and
      87 LCL genes uniquely important for their growth and survival. LCL hits were
      enriched for EBV-induced genes, including viral super-enhancer targets. Our
      systematic approach uncovered key mechanisms by which EBV oncoproteins activate
      the PI3K/AKT pathway and evade tumor suppressor responses. LMP1-induced cFLIP was
      found to be critical for LCL defense against TNFalpha-mediated programmed cell
      death, whereas EBV-induced BATF/IRF4 were critical for BIM suppression and MYC
      induction in LCLs. Finally, EBV super-enhancer-targeted IRF2 protected LCLs
      against Blimp1-mediated tumor suppression. Our results identify viral
      transformation-driven synthetic lethal targets for therapeutic intervention.

PMID- 28494240
TI  - Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant
      Enterococcus faecium.
AB  - Antibiotic-mediated microbiota destruction and the consequent loss of
      colonization resistance can result in intestinal domination with vancomycin
      resistant Enterococcus (VRE), leading to bloodstream infection in hospitalized
      patients. Clearance of VRE remains a challenging goal that, if achieved, would
      reduce systemic VRE infections and patient-to-patient transmission. Although
      obligate anaerobic commensal bacteria have been associated with colonization
      resistance to VRE, the specific bacterial species involved remain undefined.
      Herein, we demonstrate that a precisely defined consortium of commensal bacteria
      containing the Clostridium cluster XIVa species Blautia producta and Clostridium
      bolteae restores colonization resistance against VRE and clears VRE from the
      intestines of mice. While C. bolteae did not directly mediate VRE clearance, it
      enabled intestinal colonization with B. producta, which directly inhibited VRE
      growth. These findings suggest that therapeutic or prophylactic administration of
      defined bacterial consortia to individuals with compromised microbiota
      composition may reduce inter-patient transmission and intra-patient dissemination
      of highly antibiotic-resistant pathogens.

PMID- 28494241
TI  - Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in
      Inflammatory Bowel Diseases.
AB  - The gut microbiome plays a central role in inflammatory bowel diseases (IBDs)
      pathogenesis and propagation. To determine whether the gut microbiome may predict
      responses to IBD therapy, we conducted a prospective study with Crohn's disease
      (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy
      (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14,
      30, and 54 after therapy initiation were assessed. Community alpha-diversity was
      significantly higher, and Roseburia inulinivorans and a Burkholderiales species
      were more abundant at baseline among CD patients achieving week 14 remission.
      Several significant associations were identified with microbial function; 13
      pathways including branched chain amino acid synthesis were significantly
      enriched in baseline samples from CD patients achieving remission. A neural
      network algorithm, vedoNet, incorporating microbiome and clinical data, provided
      highest classifying power for clinical remission. We hypothesize that the
      trajectory of early microbiome changes may be a marker of response to IBD
      treatment.

PMID- 28494242
TI  - Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human
      Neutrophils.
AB  - Neutrophils are the first line of defense against bacterial infections, and the
      generation of reactive oxygen species is a key part of their arsenal. Pathogens
      use detoxification systems to avoid the bactericidal effects of reactive oxygen
      species. Here we demonstrate that the Gram-negative pathogen Pseudomonas
      aeruginosa is susceptible to reactive oxygen species but actively blocks the
      reactive oxygen species burst using two type III secreted effector proteins, ExoS
      and ExoT. ExoS ADP-ribosylates Ras and prevents it from interacting with and
      activating phosphoinositol-3-kinase (PI3K), which is required to stimulate the
      phagocytic NADPH-oxidase that generates reactive oxygen species. ExoT also
      affects PI3K signaling via its ADP-ribosyltransferase activity but does not act
      directly on Ras. A non-ribosylatable version of Ras restores reactive oxygen
      species production and results in increased bacterial killing. These findings
      demonstrate that subversion of the host innate immune response requires ExoS
      mediated ADP-ribosylation of Ras in neutrophils.

PMID- 28494243
TI  - A Rab20-Dependent Membrane Trafficking Pathway Controls M. tuberculosis
      Replication by Regulating Phagosome Spaciousness and Integrity.
AB  - The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within
      phagosomes and also disrupts these organelles to access the cytosol. The host
      pathways and mechanisms that contribute to maintaining Mtb phagosome integrity
      have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb
      containing phagosomes and identified an interferon-gamma-stimulated and Rab20
      dependent membrane trafficking pathway in macrophages that maintains Mtb in
      spacious proteolytic phagolysosomes. This pathway functions to promote endosomal
      membrane influx in infected macrophages, and is required to preserve Mtb
      phagosome integrity and control Mtb replication. Rab20 is specifically and
      significantly upregulated in the sputum of human patients with active
      tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of
      defense that promotes maintenance of Mtb within intact membrane-bound
      compartments for efficient elimination.

PMID- 28494244
TI  - Quorum Sensing Attenuates Virulence in Sodalis praecaptivus.
AB  - Sodalis praecaptivus is a close relative and putative environmental progenitor of
      the widely distributed, insect-associated, Sodalis-allied symbionts. Here we show
      that mutant strains of S. praecaptivus that lack genetic components of a quorum
      sensing (QS) apparatus have a rapid and potent killing phenotype following
      microinjection into an insect host. Transcriptomic and genetic analyses indicate
      that insect killing occurs as a consequence of virulence factors, including
      insecticidal toxins and enzymes that degrade the insect integument, which are
      normally repressed by QS at high infection densities. This method of regulation
      suggests that virulence factors are only utilized in early infection to initiate
      the insect-bacterial association. Once bacteria reach sufficient density in host
      tissues, the QS circuit represses expression of these harmful genes, facilitating
      a long-lasting and benign association. We discuss the implications of the
      functionality of this QS system in the context of establishment and evolution of
      mutualistic relationships involving these bacteria.

PMID- 28494246
TI  - Catalytic hydrodechlorination of triclosan using a new class of anion-exchange
      resin supported palladium catalysts.
AB  - We prepared a new class of anion-exchange-resin supported Pd catalysts for
      efficient hydrodechlorination of triclosan in water. The catalysts were prepared
      through an initial ion-exchange uptake of PdCl42- and subsequent reduction of
      Pd(II) to Pd(0) nanoparticles at ambient temperature. Two standard strong-base
      anion exchange resins (IRA-900 and IRA-958) with different matrices (polystyrene
      and polyacrylic) were chosen as the supports. SEM and TEM images showed that
      Pd(0) nanoparticles were evenly attached on the resin surface with a mean size of
      3-5 nm. The resin supported Pd catalysts (Pd@IRA-900 and Pd@IRA-958) were able to
      facilitate rapid and complete hydrodechlorination of triclosan. At a Pd loading
      of 2.0 wt.%, the observed pseudo first-order rate constant (kobs) was 1.25 +/-
      0.06 and 1.6 +/- 0.1 L/g/min for Pd@IRA-900 and Pd@IRA-958, respectively. The
      catalysts were more resistant to Cl- poisoning and natural organic matter fouling
      than other supported-Pd catalysts. The presence of 10 mM NaCl suppressed the kobs
      value by 31% and 23% for Pd@IRA-900 and Pd@IRA-958, whereas the presence of humic
      acid at 30 mg/L as TOC lowered the rates by 28% and 27%, respectively. The better
      performance of Pd@IRA-958 was attributed to the polymeric matrix properties
      (i.e., hydrophobicity, pore size, and surface area) as well as Pd particle size.
      GC/MS analyses indicated that very low concentrations of chlorinated
      intermediates were detected in the early stage of the hydrodechlorination
      process, with 2-phenoxyphenol being the main byproduct. The catalysts can be
      repeatedly used in multiple operations without significant bleeding. The
      catalysts eliminate the need for calcination in preparing conventional supported
      catalysts, and the resin supports conveniently facilitate control of Pd loading
      and material properties.

PMID- 28494247
TI  - Removal of micropollutants in biofilters: Hydrodynamic effects on biofilm
      assembly and functioning.
AB  - Global water resources contain a variety of micropollutants (MPs), including
      pharmaceuticals, personal care products, and pesticides. This study investigated
      the removal of MPs during drinking water production by means of biofiltration.
      The objective of this work was to investigate the influence of hydrodynamics on
      biofilm growth and development in a biofiltration process and the consequent
      effect on MP biotransformation rates. We operated three groups of biofiltration
      columns continuously for 381 days under three distinct hydrodynamic regimes
      (superficial velocity: 10, 20, 40 cm h-1) and fed them a mixture of 29
      micropollutants at low concentrations. Total protein concentrations were used as
      a surrogate measurement for attached biomass and periodic tracer experiments were
      conducted to estimate dispersivity and assess changes in the depth of the
      biological zone in each biofilter. These data revealed significant differences in
      biofilm assembly among the biofilters; higher superficial velocities led to less
      concentrated surface biomass but a deeper biological zone and more total biomass.
      Eleven of the 29 MPs were biotransformed and nine of those could be evaluated to
      estimate biotransformation rates. The second-order rate constants for all nine
      MPs were not significantly different among the hydrodynamic regimes. However, a
      depth-based analysis of biotransformation rates revealed significantly greater
      second-order rate constants for 5 of the MPs at increasing biofilter depths,
      suggesting that sparse microbial communities found in deeper and more
      oligotrophic biofilters had a greater activity for the biotransformation of these
      MPs. The identification of several transformation products at similar relative
      distributions suggests that the greater activity was not the result of changing
      metabolic processes under more oligotrophic conditions. These results improve our
      fundamental understanding of biofilm assembly and functioning in biofiltration
      processes.

PMID- 28494248
TI  - NLR diversity, helpers and integrated domains: making sense of the NLR IDentity.
AB  - Plant innate immunity relies on genetically predetermined repertoires of immune
      receptors to detect pathogens and trigger an effective immune response. A large
      proportion of these receptors are from the Nucletoide Binding Leucine Rich Repeat
      (NLR) gene family. As plants live longer than most pathogens, maintaining
      diversity of NLRs and deploying efficient 'pathogen traps' is necessary to
      withstand the evolutionary battle. In this review, we summarize the sources of
      diversity in NLR plant immune receptors giving an overview of genomic, regulatory
      as well as functional studies, including the latest concepts of NLR helpers and
      NLRs with integrated domains.

PMID- 28494245
TI  - Global Reprogramming of Host Kinase Signaling in Response to Fungal Infection.
AB  - Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular
      lifestyle is important for virulence. Host mechanisms controlling fungal
      phagocytosis and replication remain obscure. Here, we perform a global
      phosphoproteomic analysis of the host response to Cryptococcus infection. Our
      analysis reveals numerous and diverse host proteins that are differentially
      phosphorylated following fungal ingestion by macrophages, thereby indicating
      global reprogramming of host kinase signaling. Notably, phagocytosis of the
      pathogen activates the host autophagy initiation complex (AIC) and the upstream
      regulatory components LKB1 and AMPKalpha, which regulate autophagy induction
      through their kinase activities. Deletion of Prkaa1, the gene encoding
      AMPKalpha1, in monocytes results in resistance to fungal colonization of mice.
      Finally, the recruitment of AIC components to nascent Cryptococcus-containing
      vacuoles (CnCVs) regulates the intracellular trafficking and replication of the
      pathogen. These findings demonstrate that host AIC regulatory networks confer
      susceptibility to infection and establish a proteomic resource for elucidating
      host mechanisms that regulate fungal intracellular parasitism.

PMID- 28494249
TI  - Evaluation of problematic psychoactive substances use in people placed in police
      custody.
AB  - INTRODUCTION AND AIMS: In France, the law states that any person held in custody
      could be examined by a doctor. The main objective of the medical examination is
      to give medical evidence of health compatibility with custody. This review
      identifies health risks such as addictive behaviour. We wanted to know which
      psychoactive substances are used in this particular population, and how
      problematic these uses are. DESIGN AND METHODS: A prospective, monocentric, open
      ended study conducted via a structured questionnaire was carried out on detainees
      who reported having taken drugs or illegal substances. Practitioners investigated
      desired effects for each substance, and characteristics of use, by means of the
      dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders,
      4th edition (American Psychiatric Association, 1994). Problematic use was
      assessed when at least 3 items of the DSM IV were positive. RESULTS: 604
      questionnaires were examined. 90.7% of questionnaires reported tobacco use, 76.2%
      cannabis, 57.3% alcohol, 12.5% psychostimulants, 10.0% opiates and 0.7%
      benzodiazepines or Z-drugs. The frequency of problematic use was 74.6% for
      opiates, 44.9% for cocaine and 25.3% for cannabis. Compared to non-problematic
      users, problematic users were older, more likely to be jobless without financial
      means, more likely to have a medical history, including a greater likelihood of
      mental illness, and more chance of undergoing prescribed medical treatment. They
      included more women and more homeless people. DISCUSSION AND CONCLUSIONS: These
      results show characteristics of psychoactive substance use in a sample of people
      in custody. Psychoactive substances mentioned by respondents are not different
      from those observed in the general population, but for certain users, the desired
      effects are far from the pharmacologically expected ones. For some, taking
      substances seems to be part of their way of life, for others it is a means to
      compensate for an underlying feeling of uneasiness. Furthermore, problematic
      users present severity criteria which seem to be greater than in psychoactive
      substance users in the general population.

PMID- 28494250
TI  - Recent developments of coumarin-containing derivatives and their anti-tubercular
      activity.
AB  - Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease
      caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily
      the lungs (pulmonary TB) apart from other vital organs. The emergence of drug
      resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant
      TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards
      currently accessible standard drugs was increased up to alarming level in the
      recent decades. In pursuit of searching new anti-TB agents, numerous of
      derivatives have been synthesized and screened for their anti-TB activity.
      Coumarins are one of the most important classes of natural products that
      exhibited various biological activities, and their derivatives regarded as a new
      class of effective anti-TB candidates owing to their potential anti-TB activity.
      Thus, coumarin skeleton has attracted great interest in the development of new
      anti-TB agents. This review outlines the advances in the application of coumarin
      containing derivatives as anti-TB agents and the critical aspects of design and
      structure-activity relationship of these derivatives.

PMID- 28494251
TI  - Nitric oxide-releasing derivatives of brefeldin A as potent and highly selective
      anticancer agents.
AB  - A series of NO-donating mono- or diester derivatives of brefeldin A were
      designed, synthesized and biologically evaluated. Some derivatives exhibited
      potent antiproliferative activity with low IC50 values. The most potent NO
      donating hybrid 13b exhibited stronger cytotoxicity against human prostate cancer
      PC-3 cells, human colon carcinoma HT-29 cells and human liver cancer HepG-2 cells
      than BFA with IC50 values of 25 nM, 160 nM and 180 nM, respectively. More
      importantly, compound 13b showed good selectivity between human normal and tumor
      liver cells with selectivity index of 33. Additionally, 13b released higher
      levels of NO in HepG-2 cells than L-02 cells. Further mechanism concerning
      cellular apoptosis showed that 13b induced apoptosis and S phase cell cycle
      arrest in HepG-2 cells. Incubation with 13b increased the number of HepG-2 cells
      with collapsed mitochondrial membrane at low concentrations in dose-dependent
      manner. In addition, by using the Human Apoptosis Protein Array kit, several
      apoptosis-related proteins, including HO-1, HO-2 and survivin, were found to be
      markedly downregulated by 13b in HepG-2 cells. Furthermore, in western blot
      assay, 13b increased the expression of Bax, Cyt c and caspase 3, and reduced the
      relative levels of Bcl-2, Bcl-xl and pro-caspase 3 in HepG-2 cells.

PMID- 28494252
TI  - Design, synthesis and primary biological evaluation of the novel 2-pyridone
      derivatives as potent non-nucleoside HBV inhibitors.
AB  - In continuation of our efforts toward the discovery of potent non-nucleoside
      hepatitis B virus (HBV) inhibitors with novel structures, we have employed
      bioisosterism and hybrid pharmacophore-based strategy to explore the chemically
      diverse space of bioactive compounds. Cytotoxicity, anti-HBV antigen secretion
      activities and anti-HBV DNA replication activity were assayed with cell counting
      kit-8 (CCK-8), enzyme linked immunosorbent assay (ELISA) and a real-time PCR,
      respectively. Some of the new compounds were able to inhibit the replication of
      HBV DNA activity in the low micromolar range. In particular, compound 8u
      displayed the most potent activity against the replication of HBV DNA with IC50
      value of 3.4 MUM. The preliminary structure-activity relationship (SAR) of these
      new compounds was investigated, which may help designing more potent molecules.

PMID- 28494253
TI  - Structure-activity relationship study of the tumour-targeting peptide A20FMDV2
      via modification of Lys16, Leu13, and N- and/or C-terminal functionality.
AB  - The 20-residue linear peptide A20FMDV2 has been shown to exhibit high selectivity
      and affinity for the tumour-related alphavbeta6 integrin and has potential as a
      vector for therapeutic drugs. However, it exhibits poor half-life in plasma in
      part due to its high susceptibility to serum proteases. In this study fourteen
      A20FMDV2 analogues incorporating non-proteinogenic substitutes of the native
      Lys16 and Leu13 residues and six A20FMDV2 analogues containing modified N- and C
      termini were synthesised to increase the half-life and activity of A20FMDV2. The
      analogues incorporating modified terminal motifs of A20FMDV2 were found to
      strongly bind to the alphavbeta6 integrin and were subsequently functionalized
      with the diethylenetriaminepentaacetic acid chelating agent to facilitate
      coupling with radioactive indium-111 for human plasma stability and in vivo
      biodistribution studies. A20FMDV2 peptide variants incorporating an N-terminal d
      Asn and C-terminal d-Thr exhibited improved relative activity in vitro and were
      less susceptible to plasma degradation.

PMID- 28494254
TI  - Design, synthesis and antimicrobial evaluation of novel benzimidazole
      incorporated sulfonamide analogues.
AB  - A novel series of benzimidazole-incorporated sulfonamide analogues were designed
      and synthesized with an effort to overcome the increasing antibiotic resistance.
      Compound 5c gave potent activities against Gram-positive bacteria and fungi, and
      2,4-dichlorobenzyl derivative 5g showed good activities against Gram-negative
      bacteria. Both of these two active molecules 5c and 5g could effectively
      intercalate into calf thymus DNA to form compound-DNA complex respectively, which
      might block DNA replication to exert their powerful antimicrobial activity.
      Molecular docking experiments suggested that compounds 5c and 5g could insert
      into base-pairs of DNA hexamer duplex by the formation of hydrogen bonds with
      guanine of DNA. The transportation behavior of these highly active compounds by
      human serum albumin (HSA) demonstrated that the electrostatic interactions played
      major roles in the strong association of active compounds with HSA, and which was
      also confirmed by the full geometry calculation optimizations.

PMID- 28494255
TI  - Design and synthesis of bis(indolyl)ketohydrazide-hydrazones: Identification of
      potent and selective novel tubulin inhibitors.
AB  - A novel series of ketohydrazide-hydrazones as analogues of naturally occurring
      coscinamides has been synthesized and evaluated for their anticancer activity
      against five cancer cell lines. Of the twenty-synthesized ketohydrazide
      hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less
      than 50% cell survival) against multiple cancer cell lines when tested at a final
      concentration of 10 MUM. IC50 of three compounds 21f, 21k and 21o was determined
      to be less than 5 MUM for all tested cancer cell lines. Compound 21k exhibited
      significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT
      cancer cell lines with IC50 values of 0.8 MUM, 0.50 MUM, 0.15 MUM, and 0.22 MUM,
      respectively. Also, 21k was found to be more selectively cytotoxic against tumor
      cells when compared to normal cells. Preliminary mechanism of action studies
      indicated that the most active compound 21k induced caspase-dependent apoptosis
      in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin
      polymerization (IC50 = 0.6 MUM).

PMID- 28494256
TI  - Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.
AB  - The dominant paradigm in drug discovery is to design ligands with maximum
      selectivity to act on individual drug targets. With the target-based approach,
      many new chemical entities have been discovered, developed, and further approved
      as drugs. However, there are a large number of complex diseases such as cancer
      that cannot be effectively treated or cured only with one medicine to modulate
      the biological function of a single target. As simultaneous intervention of two
      (or multiple) cancer progression relevant targets has shown improved therapeutic
      efficacy, the innovation of multi-targeted drugs has become a promising and
      prevailing research topic and numerous multi-targeted anticancer agents are
      currently at various developmental stages. However, most multi-pharmacophore
      scaffolds are usually discovered by serendipity or screening, while rational
      design by combining existing pharmacophore scaffolds remains an enormous
      challenge. In this review, four types of multi-pharmacophore modes are discussed,
      and the examples from literature will be used to introduce attractive lead
      compounds with the capability of simultaneously interfering with different enzyme
      or signaling pathway of cancer progression, which will reveal the trends and
      insights to help the design of the next generation multi-targeted anticancer
      agents.

PMID- 28494257
TI  - Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: Synthesis,
      characterization and anticancer activity.
AB  - Cancer treatment still requires new compounds to be discovered. Chalcone and its
      derivatives exhibit anticancer potential in different cancer cells. A new series
      of benzofuran substituted chalcone derivatives was synthesized by the base
      catalyzed Claisen-Schmidt reaction of the 1-(7-ethoxy-1-benzofuran-2-yl) ethanone
      with different aromatic aldehydes to yield 1-(7-ethoxy-1-benzofuran-2-yl)
      substituted chalcone derivatives 3a-j. The derivatives were characterized by
      elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy techniques. The anti
      growth effect of chalcone compounds was tested in breast cancer (MCF-7), non
      small cell lung cancer (A549) and prostate cancer (PC-3) cell lines by the SRB
      and ATP cell viability assays. Apoptosis was detected by mitochondrial membrane
      potential, Annexin V staining and caspase 3/7 activity. Formation of reactive
      oxygen species was determined by DCFDA. The results revealed that chalcone
      derivatives have anticancer activity with especially chalcone derivative 3a
      showing cytotoxic effects on cancer cells. In addition, chalcone derivative 3a
      induced apoptosis through caspase dependent pathways in prostate, lung and breast
      cancer cells.

PMID- 28494258
TI  - Stress-related psychosocial factors at work, fatigue, and risky driving behavior
      in bus rapid transport (BRT) drivers.
AB  - INTRODUCTION: There is consistent scientific evidence that professional drivers
      constitute an occupational group that is highly exposed to work related
      stressors. Furthermore, several recent studies associate work stress and fatigue
      with unsafe and counterproductive work behaviors. This study examines the
      association between stress-related work conditions of Bus Rapid Transport (BRT)
      drivers and risky driving behaviors; and examines whether fatigue is a mechanism
      that mediates the association between the two. METHOD: A sample of 524 male Bus
      Rapid Transit (BRT) operators were drawn from four transport companies in Bogota,
      Colombia. The participants answered a survey which included an adapted version of
      the Driver Behavior Questionnaire (DBQ) for BRT operators, as well as the Effort
      Reward Imbalance and Job Content Questionnaires, the Subjective Fatigue subscale
      of the Checklist Individual Strength (CIS) and the Need for Recovery after Work
      Scale (NFR). RESULTS: Utilizing Structural Equation Models (SEM) it was found
      that risky driving behaviors in BRT operators could be predicted through job
      strain, effort-reward imbalance and social support at work. It was also found
      that fatigue and need for recovery fully mediate the associations between job
      strain and risky driving, and between social support and risky driving, but not
      the association between effort/reward imbalance (ERI) and risky driving.
      CONCLUSIONS: The results of this study suggest that a) stress related working
      conditions (Job Strain, Social Support and ERI) are relevant predictors of risky
      driving in BRT operators, and b) that fatigue is the mechanism which links
      another kind of stress related to working conditions (job strain and low social
      support) with risky driving. The mechanism by which ERI increases risky driving
      in BRT operators remains unexplained. PRACTICAL APPLICATIONS: This research
      suggests that in addition to the individual centered stress-reduction
      occupational programs, fatigue management interventions aimed to changing some
      working conditions may reduce risky driving behaviors and promote safety in the
      professional drivers' jobs and on the road.

PMID- 28494259
TI  - Mechanisms underlying cognitive conspicuity in the detection of cyclists by car
      drivers.
AB  - OBJECTIVE: The aim of this study was to evaluate the visibility of cyclists for
      motorists in a simulated car driving task. BACKGROUND: In several cases involving
      collisions between cars and cyclists, car drivers failed to detect the latter in
      time to avoid collision because of their low conspicuity. METHOD: 2 groups of
      motorists (29.2 years old), including 12 cyclist-motorists and 13 non-cyclist
      motorists, performed a vulnerable road user detection task in a car-driving
      simulator. They had to detect cyclists and pedestrians in an urban setting and
      evaluate the realism of the cyclists, the traffic, the city, the infrastructure,
      the car driven and the situations. Cyclists appeared in critical situations
      derived from previous accounts given by injured cyclists and from cyclists'
      observations in real-life situations. Cyclist's levels of visibility for car
      drivers were either high or low in these situations according to the cyclists.
      RESULTS: Realism scores were similar and high in both groups. Cyclist-motorists
      had fewer collisions with cyclists and detected cyclists at a greater distance in
      all situations, irrespective of cyclist visibility. Several mechanisms underlying
      the cognitive conspicuity of cyclists for car drivers were considered.
      CONCLUSION: The attentional selection of a cyclist in the road environment during
      car driving depends on top-down processing. APPLICATION: We consider the
      practical implications of these results for the safety of vulnerable road users
      and future directions of research.

PMID- 28494260
TI  - Examination of the reliability of the crash modification factors using empirical
      Bayes method with resampling technique.
AB  - There have been plenty of studies intended to use different methods, for example,
      empirical Bayes before-after methods, to get accurate estimation of CMFs. All of
      them have different assumptions toward crash count if there was no treatment.
      Additionally, another major assumption is that multiple sites share the same true
      CMF. Under this assumption, the CMF at an individual intersection is randomly
      drawn from a normally distributed population of CMFs at all intersections. Since
      CMFs are non-zero values, the population of all CMFs might not follow normal
      distributions, and even if it does, the true mean of CMFs at some intersections
      may be different from that at others. Therefore, a bootstrap method based on
      before-after empirical Bayes theory was proposed to estimate CMFs, but it did not
      make distributional assumptions. This bootstrap procedure has the added benefit
      of producing a measure of CMF stability. Furthermore, based on the bootstrapped
      CMF, a new CMF precision rating method was proposed to evaluate the reliability
      of CMFs. This study chose 29 urban four-legged intersections as treated sites,
      and their controls were changed from stop-controlled to signal-controlled.
      Meanwhile, 124 urban four-legged stop-controlled intersections were selected as
      reference sites. At first, different safety performance functions (SPFs) were
      applied to five crash categories, and it was found that each crash category had
      different optimal SPF form. Then, the CMFs of these five crash categories were
      estimated using the bootstrap empirical Bayes method. The results of the
      bootstrapped method showed that signalization significantly decreased Angle+Left
      Turn crashes, and its CMF had the highest precision. While, the CMF for Rear-End
      crashes was unreliable. For KABCO, KABC, and KAB crashes, their CMFs were proved
      to be reliable for the majority of intersections, but the estimated effect of
      signalization may be not accurate at some sites.

PMID- 28494261
TI  - Relationship between physical performance and self-reported function in healthy
      individuals across the lifespan.
AB  - BACKGROUND: Functional outcome measures in clinical trials of musculoskeletal
      conditions need to be meaningful to individuals. OBJECTIVES: To investigate the
      relationship between physical performance and self/proxy-reported function in
      1000 healthy children and adults. DESIGN: Cross-sectional observational study
      (1000 Norms Project). METHODS: One thousand males and females aged 3-101 years,
      healthy by self-report and without major physical disability, were recruited.
      Twelve performance-based tests were analysed: vertical and long jump, two hand
      dexterity tests, four balance tests, stepping reaction time, 30-second chair
      stand, timed up-and-down stairs, and six-minute walk. Self/proxy-reported
      function was assessed using the Infant-Toddler Quality of Life questionnaire,
      Child Health Questionnaire, Assessment of Quality of Life (AQoL)-6D Adolescent,
      AQoL-8D, International Physical Activity Questionnaire and work ability question.
      Bivariate and multivariate correlational analyses were constructed for infants (3
      4y), children (5-10y), adolescents (11-17y), adults (18-59y) and older adults
      (60+). RESULTS/FINDINGS: Socio-demographic characteristics were similar to the
      Australian population. Among infants/children, greater jump and sit-to-stand
      performance correlated with higher proxy-reported function (p < 0.05). There were
      no significant relationships observed for adolescents (p > 0.05). Greater jump,
      dexterity, balance, reaction time, sit-to-stand, stair-climbing and six-minute
      walk performance correlated with higher self-reported function in adults (r = 
      0.097 to.231; p < 0.05) and older adults (r = -0.135 to 0.625; p < 0.05).
      Multivariate regression modelling revealed a collection of independent
      performance measures explaining up to 46% of the variance in self/proxy-reported
      function. CONCLUSIONS: Many performance-based tests were significantly associated
      with self/proxy-reported function. We have identified a set of physical measures
      which could form the basis of age-appropriate functional scales for clinical
      trials of musculoskeletal conditions.

PMID- 28494262
TI  - Repositioning error, pressure pain threshold, catastrophizing and anxiety in
      adolescents with chronic idiopathic neck pain.
AB  - BACKGROUND: Impaired proprioception, increased pain sensitivity, higher levels of
      anxiety and catastrophizing are present in adults with chronic idiopathic neck
      pain. Despite the high prevalence of neck pain, studies in adolescents are
      scarce. OBJECTIVES: The main aim was to compare pressure pain thresholds (PPTs)
      and joint repositioning error (JRE) between adolescents with chronic idiopathic
      neck pain and adolescents without neck pain. Secondary aims were to compare these
      groups for catastrophizing and anxiety and to investigate the association between
      PPTs, JRE and psychosocial variables and pain characteristics. METHODS: 80
      adolescents (40 with and 40 without chronic neck pain) were assessed for: neck
      repositioning error, neck, upper trapezius and tibialis anterior PPTs, anxiety
      and catastrophizing. Neck pain was characterized in terms of intensity,
      frequency, duration and associated disability. MANCOVA was used for between group
      comparisons and Pearson and Spearman coefficients for correlational analysis.
      RESULTS: Adolescents with neck pain showed higher levels of catastrophizing (p <
      0.001) and anxiety (trait: p < 0.001; state: p = 0.028), lower PPTs (p < 0.001)
      and higher JRE (p < 0.001) than asymptomatic controls. Pain intensity, frequency
      and duration were moderately correlated with anxiety, and disability was
      moderately correlated with anxiety (r between 0.43 and 0.50, p < 0.05) and
      catastrophizing (r = 0.40, p < 0.05). CONCLUSIONS: This study suggests that
      functional changes and maladaptive cognitive processes are present in adolescents
      with neck pain aged 16-18 years old. These findings need to be replicated in
      future studies.

PMID- 28494263
TI  - Zipf's Law of Abbreviation and the Principle of Least Effort: Language users
      optimise a miniature lexicon for efficient communication.
AB  - The linguist George Kingsley Zipf made a now classic observation about the
      relationship between a word's length and its frequency; the more frequent a word
      is, the shorter it tends to be. He claimed that this "Law of Abbreviation" is a
      universal structural property of language. The Law of Abbreviation has since been
      documented in a wide range of human languages, and extended to animal
      communication systems and even computer programming languages. Zipf hypothesised
      that this universal design feature arises as a result of individuals optimising
      form-meaning mappings under competing pressures to communicate accurately but
      also efficiently-his famous Principle of Least Effort. In this study, we use a
      miniature artificial language learning paradigm to provide direct experimental
      evidence for this explanatory hypothesis. We show that language users optimise
      form-meaning mappings only when pressures for accuracy and efficiency both
      operate during a communicative task, supporting Zipf's conjecture that the
      Principle of Least Effort can explain this universal feature of word length
      distributions.

PMID- 28494265
TI  - Intramyocardial fate and effect of iron nanoparticles co-injected with MACS(r)
      purified stem cell products.
AB  - BACKGROUND: Magnetic activated cell sorting (MACS(r)) is routinely used to
      isolate stem cell subpopulations intended for the treatment of cardiovascular
      diseases. In strong contrast, studies examining the amount, effect and
      intramyocardial distribution of iron nanoparticles used for magnetic cell
      labelling are missing, although iron excess can cause functional disorders in the
      heart. METHODS AND RESULTS: CD133+ haematopoietic and CD271+ mesenchymal stem
      cells were purified from bone marrow using automatically and manually MACS(r)
      based systems. Flow cytometric measurements demonstrated a rapid loss of MACS(r)
      MicroBeads from cells under culture conditions, while storage under hypothermic
      conditions decelerated their detachment. Moreover, an average loading of ~11 fg
      iron/cell caused by magnetic labelling was determined in magnetic particle
      spectroscopy. Importantly, hemodynamic measurements as well as histological
      examinations using a myocardial ischemia/reperfusion mouse model showed no
      influence of MACS(r) MicroBeads on cardiac regeneration, while the
      transplantation of stem cells caused a significant improvement. Furthermore,
      immunostainings demonstrated the clearance of co-injected iron nanoparticles from
      stem cells and the surrounding heart tissue within 48 h post transplantation.
      CONCLUSIONS: Our results indicate that iron amounts typically co-injected with
      MACS(r) purified stem cells do not harm cardiac functions and are cleared from
      heart tissue within a few hours. Therefore, we conclude that MACS(r) MicroBeads
      exhibit a good compatibility in the cardiac environment.

PMID- 28494266
TI  - Pelvic organ prolapse surgery in Finland from 1987 to 2009: A national register
      based study.
AB  - OBJECTIVES: To establish the trends in pelvic floor surgery in Finnish female
      population and to evaluate the age-specific incidence as well as the lifetime
      risk for pelvic organ prolapse surgery. STUDY DESIGN: We conducted a population
      based register study, which includes all Finnish women (n=77 906), who underwent
      surgery for pelvic organ prolapse in Finland 1987-2009. The women were identified
      in the Care Register for Health Care based on the procedure codes. Number of
      procedures, age-adjusted incidence, age-specific incidence, cumulative incidence,
      lifetime risk were calculated. RESULTS: A total of 93 226 surgical procedures for
      POP were performed. The age-adjusted incidence of prolapse surgery was 1.3/1000
      women in 1987. After that there was an increase which peaked in 1996 with
      1.9/1000, and a decline thereafter back to 1.3/1000 in 2009. The lifetime risk
      for a woman to have undergone at least one surgical procedure for prolapse was
      12.8%. Surgery was most common within women aged 70 to 79 years, followed by
      women aged 60 to 69 years. The most popular procedure until 1991 was cervix
      amputation with colporraphies, surpassed thereafter by colporraphies only or with
      combined vaginal hysterectomy. CONCLUSION: Surgery for pelvic organ prolapse is
      common and more than every tenth woman underwent such surgery during lifetime.

PMID- 28494264
TI  - High yield, scalable and remotely drug-loaded neutrophil-derived extracellular
      vesicles (EVs) for anti-inflammation therapy.
AB  - Extracellular vesicles (EVs) are nanoscale membrane-formed compartments naturally
      secreted from cells, which are intercellular mediators regulating physiology and
      pathogenesis, therefore they could be a novel therapeutic carrier for targeted
      delivery. However, the translation of EVs is hindered by the heterogeneous
      composition, low yield, inefficient drug loading and unlikely scalability. Here
      we report a strategy to generate EVs using nitrogen cavitation (NC-EVs) that
      instantly disrupts neutrophils to form nanosized membrane vesicles. NC-EVs are
      similar to naturally secreted EVs (NS-EVs), but contain less subcellular
      organelles and nuclear acids. The production of NC-EVs was increased by 16 folds
      and is easy to scale up for clinical use compared to NS-EVs. To examine the
      usefulness of NC-EVs as a drug delivery platform, piceatannol (an anti
      inflammation drug) was remotely loaded in NC-EVs via the pH gradient. We found
      that piceatannol-loaded NC-EVs dramatically alleviated acute lung
      inflammation/injury and sepsis induced by lipopolysaccharide (LPS). Our studies
      reveal that nitrogen cavitation is a novel approach to efficiently generate EVs
      from any cell type and could be exploited for personalized nanomedicine.

PMID- 28494267
TI  - Advanced glycation products' levels and mechanical properties of vaginal tissue
      in pregnancy.
AB  - OBJECTIVES: Non-enzymatic glycation is closely associated with altered mechanical
      properties of connective tissue. Pregnancy, marked with high levels of female
      hormones, confers unique alteration to the mechanical properties of pelvic
      connective tissues in order to meet their physiological demands. However, there
      are few studies on glycation content and its influence on the mechanical
      properties of pelvic connective tissues during pregnancy. We hypothesise that the
      glycation content in pelvic tissues will change with a corresponding alteration
      in their mechanical properties, and that these changes are influenced by hormone
      levels. This study aims to investigate the correlation of vaginal tissue
      glycation content and mechanical property changes during pregnancy in association
      with the expression of a key pregnancy hormone (oestrogen) receptor, and an
      antioxidant enzyme, glyoxalase I. STUDY DESIGN: A rat vaginal tissue model
      (tissues from non-pregnant and E15-E18 (last trimester) pregnant rats) was used
      in this study. Mechanical characteristics of vaginal tissues were analysed by a
      ball-indentation technique while modulus and morphology of the collagen fibrils
      within the tissues were measured with atomic force microscopy. A glycation
      marker, pentosidine, was quantified by a high performance liquid chromatography.
      The expression of oestrogen receptor and glyoxalase I in the tissue was qualified
      by immunochemical staining. The glycosaminoglycan (GAG) concentration difference
      in the tissues were quantified by a biochemical assay. RESULTS: Pregnant rat
      vaginal tissue was characterised by significantly lower amounts of pentosidine,
      higher oestrogen receptor and glyoxalase I expression with larger creep, lower
      elastic modulus, larger fibril diameter and higher GAG content than their non
      pregnant counterpart. There was a negative correlation between pentosidine and
      vaginal tissue creep. CONCLUSION: There was a reduction in vaginal tissue
      pentosidine in pregnancy with an associated increase in oestrogen receptor and
      glyoxalase I immunoexpression. Reduced glycation was associated with increased
      creeping of vaginal tissue. Oestrogen may therefore play a role in the increase
      of the vaginal wall's capacity to stretch through glyoxalase I up-regulation and
      subsequent glycation reduction. The new insight of the correlation of women's
      oestrogen level, glycation reaction and pelvic tissue mechanical property from
      this study may enhance our understanding of some pelvic organ diseases.

PMID- 28494268
TI  - Pregnancy outcome and cord blood cotinine level: A cross-sectional comparative
      study between secondhand smokers and non-secondhand smokers.
AB  - OBJECTIVE: To compare the pregnancy outcome and cord blood cotinine levels
      between secondhand smokers and non-secondhand smokers. STUDY DESIGN: This was a
      cross-sectional comparative study in a Malaysian tertiary obstetric hospital
      involving 200 non-smoking pregnant women at term, of whom 100 were secondhand
      smokers and 100 were non-secondhand smokers. Those with multiple pregnancies,
      with a body mass index (BMI) of more than 30kg/m2 or who delivered by Caesarean
      section were excluded. The participants' basic demographic details, delivery
      details, neonatal outcome and placental weight were recorded. Umbilical cord
      blood samples were obtained, and cord blood cotinine levels were measured with a
      Cotinine ELISA kit. The primary outcomes were baby's birth weight, length, and
      head circumference, Apgar score at 5min and placental weight. The secondary
      outcome was difference in cord blood cotinine levels between the two groups and
      the correlation of these differences with the neonatal outcome. RESULTS: The
      secondhand smoker group had significantly lower baby weight (2.94+/-0.31kg vs
      3.05+/-0.40kg), head circumference (30.87+/-2.35cm vs 37.13+/-2.36cm), length
      (46.58+/-1.95cm vs 51.53+/-2.05cm) and placental weight (520+/-73.5g vs 596+/
      61.3g) and significantly higher cord blood cotinine levels (16.35+/-12.84ng/mL vs
      0.56+/-0.22ng/mL). Cord blood cotinine levels had significant negative
      correlations with placental weight (r=-0.461), baby's weight (r=-0.297), baby's
      head circumference (r=-0.501) and baby's length (r=-0.374). CONCLUSION:
      Secondhand smoke increases the incidence of adverse pregnancy outcomes
      (newborns'anthropometric measurements and placental weight) and causes higher
      cord blood cotinine levels.

PMID- 28494269
TI  - Medical conditions associated with recurrent miscarriage-Is BMI the tip of the
      iceberg?
AB  - BACKGROUND: In contrast to sporadic miscarriage, recurrent miscarriage (RM) is a
      rare entity which affects 1% of couples attempting conception. It is distressing
      for couples and healthcare professionals as the aetiology is unclear with limited
      treatment options. Apart from anti-phospholipid syndrome (APS), the strength of
      associations between RM and commonly investigated endocrine, autoimmune,
      thrombophilic and uterine structural abnormalities remains uncertain and
      variable. OBJECTIVES: To assess the prevalence of commonly investigated medical
      conditions associated with RM. STUDY DESIGN: A 9-year retrospective analysis of a
      prospectively collected database was conducted for 592 patients seen between 2008
      and 2016, in tertiary level RM clinic in South Africa. RESULTS: In this period,
      592 patients were assessed. The mean age was 29.73+/-5.46 (mean+/-SD), gravidity
      4.6+/-1.82 and parity 0.98+/-1.05. The mean number of miscarriages per patient
      was 3.34+/-1.63, of which two-thirds (61.3%) were in the first trimester, a third
      (33%) in the second trimester and intrauterine fetal deaths (IUFDs) constituted
      6% of total losses. Of the 50% of patients with no identified associated
      disorders, 15% were unexplained (investigations complete but no associations
      found), 10% became pregnant during investigation (investigations incomplete) and
      25% were lost to follow-up (investigations incomplete). Nearly forty percent
      (38%) of patients had an associated endocrine disorder (22% PCOS, 11% IGT, 3%
      Diabetes Mellitus and 2% Thyroid Dysfunction) and 10% a uterine factor (4%
      Cervical Incompetence, 2% Fibroids, 2% Synechiae and 2% Anomalies). APS and
      Thrombophilias constituted 3% and 2% of patients respectively. The BMI (mean+/
      SD) amongst patients with Unexplained RM, PCOS and IGT were 28.85+/-5.95, 30.86+/
      7.79 and 33.40+/-6.47 respectively. Patients with IGT had significantly higher
      mean BMI in comparison to those with Unexplained RM (p<0.0001)*** and PCOS
      (p<0.001)**. CONCLUSION: PCOS, IGT and Type II Diabetes are all likely surrogates
      for elevated BMI and constitute 70% of those women with RM and identified
      associated medical disorders. In our population, BMI seems to have a substantial
      impact on recurrent pregnancy loss and future studies should interrogate its
      effect on recurrent miscarriage.

PMID- 28494270
TI  - Vaginal wind: A literature review.
AB  - OBJECTIVE: In the medical literature, there is little known about vaginal wind,
      though from clinical expertise, it turns out to be a consistent and underreported
      problem. The aim of this review was to collect the available literature about the
      different aspects of vaginal wind. STUDY DESIGN: A systematic literature search
      was conducted using three databases until December 2015. The search strategy was
      built using relevant synonyms of vaginal wind. Study characteristics were
      extracted. Risk of bias, the quality of the relevant studies and the level of
      evidence was judged. RESULTS: Eleven studies met the inclusion criteria. Vaginal
      wind occurs on random movements and during or after coitus. The prevalence ranges
      from one to 69%. The pathophysiology is unclear and the incidence unknown. Known
      risk factors are vaginal delivery and urinary incontinence. Provoking factors are
      coitus, digital stimulation, cunnilingus and exercising. Female sexual function
      is decreased. The sexual function of male partners with vaginal wind is not
      influenced. Overall vaginal wind leads to a decrease in the quality of live and
      can have cause social isolation. The treatment is related to the cause and mainly
      not successful. Tampons can be used for treatment as well as prevention.
      CONCLUSION: Vaginal wind is an underestimated health issue with a severe impact
      on sexual functioning. Adequate research is needed regarding the influence of
      sexual activity, weight, age, parity, the underlying pathophysiological
      mechanisms, prevention and treatment.

PMID- 28494271
TI  - Motion-robust parameter estimation in abdominal diffusion-weighted MRI by
      simultaneous image registration and model estimation.
AB  - Quantitative body DW-MRI can detect abdominal abnormalities as well as monitor
      response-to-therapy for applications including cancer and inflammatory bowel
      disease with increased accuracy. Parameter estimates are obtained by fitting a
      forward model of DW-MRI signal decay to the observed data acquired with several b
      values. The DW-MRI signal decay models typically used do not account for
      respiratory, cardiac and peristaltic motion, however, which may deteriorate the
      accuracy and robustness of parameter estimates. In this work, we introduce a new
      model of DW-MRI signal decay that explicitly accounts for motion. Specifically,
      we estimated motion-compensated model parameters by simultaneously solving image
      registration and model estimation (SIR-ME) problems utilizing the interdependence
      of acquired volumes along the diffusion-weighting dimension. To accomplish this,
      we applied the SIR-ME model to the in-vivo DW-MRI data sets of 26 Crohn's disease
      (CD) patients and achieved improved precision of the estimated parameters by
      reducing the coefficient of variation by 8%, 24% and 8% for slow diffusion (D),
      fast diffusion (D*) and fast diffusion fraction (f) parameters respectively,
      compared to parameters estimated with independent registration in normal
      appearing bowel regions. Moreover, the parameters estimated with the SIR-ME model
      reduced the error rate in classifying normal and abnormal bowel loops to 12% for
      D and 10% for f parameter with a reduction in error rate by 13% and 11% for D and
      f parameters, respectively, compared to the error rate in classifying parameter
      estimates obtained with independent registration. The experiments in DW-MRI of
      liver in 20 subjects also showed that the SIR-ME model improved the precision of
      parameter estimation by reducing the coefficient of variation to 7% for D, 23%
      for D*, and 8% for the f parameter. Using the SIR-ME model, the coefficient of
      variation was reduced by 4%, 14% and 6% for D, D* and f parameters, respectively,
      compared to parameters estimated with independent registration. These results
      demonstrate that the proposed SIR-ME model improves the accuracy and robustness
      of quantitative body DW-MRI in characterizing tissue microstructure.

PMID- 28494272
TI  - A new inverse method for estimation of in vivo mechanical properties of the
      aortic wall.
AB  - The aortic wall is always loaded in vivo, which makes it challenging to estimate
      the material parameters of its nonlinear, anisotropic constitutive equation from
      in vivo image data. Previous approaches largely relied on either computationally
      expensive finite element models or simplifications of the geometry or material
      models. In this study, we investigated a new inverse method based on aortic wall
      stress computation. This approach consists of the following two steps: (1)
      computing an "almost true" stress field from the in vivo geometries and loading
      conditions, (2) building an objective function based on the "almost true" stress
      fields, constitutive equations and deformation relations, and estimating the
      material parameters by minimizing the objective function. The method was
      validated through numerical experiments by using the in vivo data from four
      ascending aortic aneurysm (AsAA) patients. The results demonstrated that the
      method is computationally efficient. This novel approach may facilitate the
      personalized biomechanical analysis of aortic tissues in clinical applications,
      such as in the rupture risk analysis of ascending aortic aneurysms.

PMID- 28494274
TI  - Personalized T cell-mediated cancer immunotherapy: progress and challenges.
AB  - Immunotherapies are yielding effective treatments for several previously
      untreatable cancers. Until recently, vaccines and adoptive cell therapies have
      been designed to target public tumor antigens common to multiple patients rather
      than private antigens specific to a single patient. Due to the difficulty of
      identifying public antigens that are expressed exclusively on tumor cells, these
      studies have yielded both clinical successes and serious immune-related adverse
      events. Multiple avenues of research now underscore the centrality of tumor
      specific mutated private antigens to endogenous anti-tumor immunity.
      Immunotherapies that target these neoantigens may enable safer and more durable
      tumor regression, but personalized targeting presents a number of challenges.
      Foremost among these is to develop processes that accelerate advancement from
      neoantigen discovery to use of these neoantigens as vaccines or as targets for
      adoptive cell therapies. Exome sequencing has facilitated discovery of
      neoantigens for melanoma and other highly mutated cancers. New technologies -
      possibly proceeding from T cell receptor repertoire sequencing - are needed to
      identify antigens for cancers with low mutational burden and few neoantigens. In
      this review, we discuss progress toward personalizing T cell-mediated
      immunotherapy for cancer as well as challenges going forward.

PMID- 28494273
TI  - Fatigue limit of monolithic Y-TZP three-unit-fixed dental prostheses: Effect of
      grinding at the gingival zone of the connector.
AB  - OBJECTIVES: To determine the fatigue limits of three-unit monolithic zirconia
      fixed dental prosthesis (FDPs) before and after grinding of the gingival areas of
      connectors with diamond burs. MATERIAL AND METHODS: FDPs were milled from pre
      sintered blocks of zirconia simulating the absence of the first mandibular molar.
      Half of the specimens were subjected to grinding, simulating clinical adjustment,
      and all of them were subjected to glazing procedure. Additional specimens were
      manufactured for roughness analysis. FDPs were adhesively cemented onto glass
      fiber reinforced epoxy resin abutments. Fatigue limits and standard deviations
      were obtained using a staircase fatigue method (n=20, 100,000 loading
      cycles/5Hz). The initial test load was 70% of the mean load-to-fracture (n=3) and
      load increments were 5% of the initial test load for both the control and ground
      specimens. Data were compared by Student's T-test (alpha<=0.05). RESULTS: Both
      the control and ground groups exhibited similar values of load-to-fracture and
      fatigue limits. Neither the surface treatments nor ageing affected the surface
      roughness of the specimens. CONCLUSIONS: The damage induced by grinding with fine
      grit diamond bur in the gingival area of the connectors did not decrease the
      fatigue limit of the three-unit monolithic zirconia FDP.

PMID- 28494275
TI  - Synthetic biological approaches for RNA labelling and imaging: design principles
      and future opportunities.
AB  - RNA is the most mercurial of all biomacromolecules. In contrast to DNA, where the
      predominant role is the storage of genetic information, the biological role of
      RNA varies; ranging from a template-based intermediary in gene expression to
      playing a direct role in catalysis. Their high turnover and metabolic lability
      makes the detection of specific sequences particularly challenging. This review
      describes the latest synthetic biological developments that enable the direct
      imaging of RNA both in vitro and in their native cellular environment.

PMID- 28494276
TI  - Prediction of ligand effects in platinum-amyloid-beta coordination.
AB  - Ligand field molecular mechanics (LFMM) and semi-empirical Parametric Model 7
      (PM7) methods are applied to a series of six PtII-Ligand systems binding to the N
      terminal domain of the amyloid-beta (Abeta) peptide. Molecular dynamics using a
      combined LFMM/Assisted Model Building with Energy Refinement (AMBER) approach is
      used to explore the conformational freedom of the peptide fragment, and
      identifies favourable platinum binding modes and peptide conformations for each
      ligand investigated. Platinum coordination is found to depend on the nature of
      the ligand, providing evidence that binding mode may be controlled by suitable
      ligand design. Boltzmann populations at 310K indicate that each Pt-Abeta complex
      has a small number of thermodynamically accessible states. Ramachandran maps are
      constructed for the sampled Pt-Abeta conformations and secondary structural
      analysis of the obtained complex structures is performed and contrasted with the
      free peptide; coordination of these platinum complexes disrupts existing
      secondary structure in the Abeta peptide and promotes formation of ligand
      specific turn-type secondary structure.

PMID- 28494277
TI  - Toxicity of Quaternary Ammonium Compounds (QACs) as single compounds and mixtures
      to aquatic non-target microorganisms: Experimental data and predictive models.
AB  - The toxic effects of five Quaternary Ammonium Compounds (QACs) that are widely
      used as active ingredients in personal care products were assessed using the
      bioluminescent bacterium Aliivibrio fischeri (formerly Vibrio fischeri)
      (Microtox(r) test system). The experimental results showed a relevant toxicity
      for almost all of the single QACs, with IC50 values lower than 1mgL-1. Analysis
      of the mode of action through the application of the Quantitative Structure
      Activity Relationship (QSAR) models indicated an a-specific reactivity for most
      of the QACs toward A. fischeri. Only hexadecyl trimethyl ammonium chloride (ATMAC
      16) behaved as a polar-narcotic, with a low reactivity toward the bacterial cell
      membrane. The concentration response curves of the different binary and
      multicomponent mixtures of QACs were also evaluated with respect to the
      predictions from the Concentration Addition (CA) and Independent Action (IA)
      models. For almost all of the binary and multicomponent mixtures (7 out of 11
      mixtures tested), an agreement between the experimental and predicted ICx was
      observed and confirmed via application of the Model Deviation Ratio (MDR). In
      four cases, some deviations from the expected behaviour were observed (potential
      antagonistic and synergistic interactions) at concentrations on the order of
      hundreds of ugL-1, which could be of environmental concern, especially in the
      case of synergistic effects. The analysis of aquatic ecotoxicity data and the few
      available values of the measured environmental concentrations (MECs) from the
      literature for wastewaters and receiving waterbodies suggest that a potential
      risk toward aquatic life cannot be excluded.

PMID- 28494278
TI  - Outcomes of ultrasound-guided axillary lymph node sampling in the absence of
      primary breast cancer.
AB  - PURPOSE: To evaluate outcomes of lymph node sampling in patients with suspicious
      axillary nodes without a diagnosis of breast cancer. MATERIALS AND METHODS: We
      retrospectively identified all axillary ultrasound-guided sampling performed at
      our institution from 2003 to 2016 in patients. without malignancy. RESULTS:
      Seventy-eight lymph nodes met inclusion criteria. Two of the 78 sampled nodes
      (2.6%) were malignant. CONCLUSION: Sampling of suspicious nodes in patients
      without a history of breast cancer rarely yields malignancy. The malignancy rate
      approaches the 2% BIRADS 3 threshold. Further data may demonstrate that short
      interval imaging follow-up is a safe alternative to sampling in this cohort.

PMID- 28494279
TI  - Gastrointestinal stromal tumor presenting as a right adnexal mass with
      histopathologic correlation.
AB  - The authors report and discuss a rare case of a gastrointestinal stromal tumor
      (GIST) in a 35-year-old female, which was pre-procedurally characterized as a
      right ovarian mass by magnetic resonance imaging (MRI) features. This manuscript
      reviews the imaging and clinical features of GISTs with pathologic correlation,
      and emphasizes how this entity may present a diagnostic challenge in certain
      anatomic regions owing in large part to its exophytic nature. This case is unique
      among similarly reported cases in that there was a "claw sign" with the right
      ovary, which provided convincing evidence of its point of origin.

PMID- 28494280
TI  - Iron mineralogy as a fingerprint of former steelmaking activities in river
      sediments.
AB  - Submerged sediment cores were collected upstream of a dam in the Orne River,
      northeastern France. This dam was built in the context of steelmaking to
      constitute a water reservoir for blast furnace cooling and wet cleaning of
      furnace smokes. The dam also enhanced sediment deposition in the upstream zone.
      This study was performed to unravel the contamination status of sediments and to
      evidence possible contribution sources. The sediment layers were analyzed for
      water content, grain size, chemical composition, crystalline phases at a bulk
      scale and poorly crystalline and amorphous phases at a sub-micrometer scale.
      Visual aspect, texture, color, and chemical and mineralogical analyses showed
      that the settled sediments were mainly composed of fine black matter, certainly
      comprising steelmaking by-products. Those materials were highly enriched with Fe,
      Zn, Pb and other trace metals, except for a relatively thin layer of surficial
      sediments that had settled more recently. Bulk mineralogy revealed crystalline
      iron minerals, such as magnetite, goethite, wuestite and pyrite, in the deep
      layers of the sediment cores. Furthermore, microscopic investigations evidenced
      the presence of ferrospheres, goethite nanoparticles and newly formed Fe
      aluminosilicates; all originating from the former steelmaking facilities. The
      variation of iron mineralogy, combined with specific chemical profiles and other
      sediment features, demonstrate the different contributions that constitute the
      sediment deposit. Furthermore, chemical and mineralogical features of goethite
      and Fe-aluminosilicates could be used as a fingerprint for such contaminated
      sediments.

PMID- 28494281
TI  - Using deltaDn-alkane as a proxy for paleo-environmental reconstruction: A good
      choice to sample at the site dominated by woods.
AB  - Some studies have demonstrated that leaf wax deltaDn-alkane values for a single
      species varied significantly with seasons. However, it is still not clear that
      the seasonality patterns of leaf wax deltaDn-alkane values in higher plants.
      Meanwhile, few efforts have been pursued to assess the effect of the light slopes
      (sunny vs. cloudy) on leaf wax deltaDn-alkane values. In this study, we
      systematically investigated plant wax deltaDn-alkane values and soil n-alkane
      deltaD values along different light slopes in different seasons (spring vs.
      autumn), as well as the relationship of n-alkane deltaD values between plant
      leaves and soil. We found that plant wax deltaDn-alkane values were D-enriched by
      ca. 200/00 in spring relative to autumn, and ca. 100/00 in the sunny slope than
      in the cloudy slope. Moreover, surface soil n-alkane deltaD values varied
      consistently with plant wax deltaDn-alkane values for different seasons and light
      slopes. More importantly, plant wax deltaDn-alkane values showed clear seasonal
      variations, but varied slightly with light slopes. The variations of plant wax
      deltaDn-alkane values can be recorded in soil n-alkane deltaDn-alkane values. In
      addition, we found that leaf wax deltaDn-alkane values in a majority of species
      differed significantly among woods, non-woods and grasses at a site. Therefore,
      we suggested a good choice to sample at the site dominated by woods when leaf wax
      deltaDn-alkane values are utilized as a proxy for the reconstruction of the
      paleoenvironment.

PMID- 28494282
TI  - Anthropogenic fibres in the Baltic Sea water column: Field data, laboratory and
      numerical testing of their motion.
AB  - Distribution of microplastics particles (MPs) in the water column is investigated
      on the base of 95 water samples collected from various depths in the Baltic Sea
      Proper in 2015-2016. Fibres are the prevalent type of MPs: 7% of the samples
      contained small films; about 40% had (presumably) paint flakes, while 63%
      contained coloured fibres in concentrations from 0.07 to 2.6 items per litre.
      Near-surface and near-bottom layers (defined as one tenth of the local depth)
      have 3-5 times larger fibre concentrations than intermediate layers. Laboratory
      tests demonstrated that sinking behaviour of a small and flexible fibre can be
      complicated, with 4-fold difference in sinking velocity for various random
      fibres' curvature during its free fall. Numerical tests on transport of fibres in
      the Baltic Sea Proper were performed using HIROMB reanalysis data (2007) for the
      horizontal velocity field and laboratory order-of-magnitude estimates for the
      sinking velocity of fibres. The model takes into account (i) motion of fibres
      together with currents, (ii) their very slow sinking, and (iii) their low re
      suspension threshold. Sensitivity of the final distribution of fibres to
      variations of those parameters is examined. These experiments are the first step
      towards modelling of transport of fibres in marine environment and they seem to
      reproduce the main features of fibres distribution quite well.

PMID- 28494283
TI  - Preliminary study of phytoremediation of brownfield soil contaminated by PAHs.
AB  - Our project was aimed at improving a brownfield in the city of Kladno, where an
      old steel producing facility used to be in operation. Ecological risk is mainly
      caused by the processing of co-products during coal production (tars, oils).
      Knowledge of toxicology and environmental aspects can help us protect human
      health and the environment. Primarily, we focused on soil sampling and
      identification of pollutants. Results showed that organic contamination on the
      site is very high. Average concentration of total petroleum carbon in the soil
      was about 13g/kg DW, which is much more than the maximum allowed concentration.
      For selection of suitable plant species for phytoremediation at the site,
      experiments were conducted in a greenhouse. Biomass growth, root morphology, and
      pigment content in the leaves of Brassica napus var. Opus-C1 and
      Sorghum*drummondii var. Honey Graze BMR plants were studied. Plant analysis
      confirmed that polyaromatic hydrocarbons (PAHs) accumulated in the shoots of both
      plant species. B. napus plants grown on Poldi soil in a greenhouse were able to
      survive the toxicity of PAHs in soil, and their ability to accumulate PAHs from
      soil was evident. However, more studies are needed to decide if the plants are
      usable for phytoremediation of this brownfield.

PMID- 28494284
TI  - Evaluating the impact of irrigation on surface water - groundwater interaction
      and stream temperature in an agricultural watershed.
AB  - Changes in groundwater discharge to streams caused by irrigation practices can
      influence stream temperature. Observations along two currently flood-irrigated
      reaches in the 640-square-kilometer upper Smith River watershed, an important
      agricultural and recreational fishing area in west-central Montana, showed a
      downstream temperature decrease resulting from groundwater discharge to the
      stream. A watershed-scale coupled surface water and groundwater flow model was
      used to examine changes in streamflow, groundwater discharge to the stream and
      stream temperature resulting from irrigation practices. The upper Smith River
      watershed was used to develop the model framework including watershed climate,
      topography, hydrography, vegetation, soil properties and current irrigation
      practices. Model results were used to compare watershed streamflow, groundwater
      recharge, and groundwater discharge to the stream for three scenarios: natural,
      pre-irrigation conditions (PreIrr); current irrigation practices involving mainly
      stream diversion for flood and sprinkler irrigation (IrrCurrent); and a
      hypothetical scenario with only groundwater supplying sprinkler irrigation
      (IrrGW). Irrigation increased groundwater recharge relative to natural PreIrr
      conditions because not all applied water was removed by crop evapotranspiration.
      Groundwater storage and groundwater discharge to the stream increased relative to
      natural PreIrr conditions when the source of irrigation water was mainly stream
      diversion as in the IrrCurrent scenario. The hypothetical IrrGW scenario, in
      which groundwater withdrawals were the sole source of irrigation water, resulted
      in widespread lowering of the water table and associated decreases in groundwater
      storage and groundwater discharge to the stream. A mixing analysis using model
      predicted groundwater discharge along the reaches suggests that stream diversion
      and flood irrigation, represented in the IrrCurrent scenario, has led to cooling
      of stream temperatures relative to natural PreIrr conditions improving fish
      thermal habitat. However, the decrease in groundwater discharge in the IrrGW
      scenario resulting from large-scale groundwater withdrawal for irrigation led to
      warmer than natural stream temperatures and possible degradation of fish habitat.

PMID- 28494285
TI  - Effects of in situ exposure to tritiated natural environments: A multi-biomarker
      approach using the fathead minnow, Pimephales promelas.
AB  - Aquatic ecosystems are chronically exposed to radionuclides as well as other
      pollutants. Increased concentrations of pollutants in aquatic environments can
      present a risk to exposed organisms, including fish. The goal of this study was
      to characterize the effects of tritium, in the context of natural environments,
      on the health of fathead minnow, Pimephales promelas. Fish were exposed to
      tritium (activity concentrations ranging from 2 to 23,000Bq/L) and also to
      various concentrations of several metals to replicate multiple-stressor
      environments. Fish were exposed for 60days, then transferred to the tritium
      background site where they stayed for another 60days. Tritium, in the forms of
      tritiated water (HTO) and organically bound tritium (OBT), and a series of fish
      health indicators were measured in fish tissues at seven time points throughout
      the 120days required to complete the exposure and the depuration phases. Results
      showed effects of environmental exposure following the increase of tritium
      activity and metals concentrations in water. The internal dose rates of tritium,
      estimated from tissue HTO and OBT activity concentrations, were consistently low
      (maximum of 0.2MUGy/h) compared to levels at which population effects may be
      expected (>100MUGy/h) and no effects were observed on survival, fish condition,
      gonado-somatic, hepato-somatic, spleno-somatic and metabolic indices (RNA/DNA,
      proteins/DNA and protein carbonylation (in gonads and kidneys)). Using
      multivariate analyses, we showed that several biomarkers (DNA damages, MN
      frequency, gamma-H2AX, SFA/MUFA ratios, lysosomal membrane integrity, AChE, SOD,
      phagocytosis and esterase activities) were exclusively correlated with fish
      tritium internal dose rate, showing that tritium induced genotoxicity, DNA repair
      activity, changes in fatty acid composition, and immune, neural and antioxidant
      responses. Some biomarkers were responding to the presence of metals, but
      overall, more biomarkers were linked to internalized tritium. The results are
      discussed in the context of multiple stressors involving metals and tritium.

PMID- 28494286
TI  - Slurry photocatalytic membrane reactor technology for removal of pharmaceutical
      compounds from wastewater: Towards cytostatic drug elimination.
AB  - The potential of photocatalytic membrane reactors (PMR) to degrade cytostatic
      drugs is presented in this work as an emerging technology for wastewater
      treatment. Cytostatic drugs are pharmaceutical compounds (PhCs) commonly used in
      cancer treatment. Such compounds and their metabolites, as well as their degraded
      by-products have genotoxic and mutagenic effects. A major challenge of cytostatic
      removal stands in the fact that most drugs are delivered to ambulant patients
      leading to diluted concentration in the municipal waste. Therefore safe
      strategies should be developed in order to collect and degrade the micro
      pollutants using appropriate treatment technologies. Degradation of cytostatic
      compounds can be achieved with different conventional processes such as chemical
      oxidation, photolysis or photocatalysis but the treatment performances obtained
      are lower than the ones observed with slurry PMRs. Therefore the reasons why
      slurry PMRs may be considered as the next generation technology will be discussed
      in this work together with the limitations related to the mechanical abrasion of
      polymeric and ceramic membranes, catalyst suspension and interferences with the
      water matrix. Furthermore key recommendations are presented in order to develop a
      renewable energy powered water treatment based on long lifetime materials.

PMID- 28494287
TI  - 137Cs contamination over Transylvania region (Romania) after Chernobyl Nuclear
      Power Plant Accident.
AB  - Following the radionuclide releases due to Chernobyl Nuclear Power Plant
      accident, various studies were completed by researchers all over the world in
      order to measure the surface contaminations by artificial radionuclides. The aim
      of this study was to evaluate 137Cs surface contamination and to create an
      inventory distribution for Transylvania region (Romania) after the Chernobyl
      event using gamma spectrometric measurements on soil samples collected from 153
      locations. The results were compared to measured data from the Danube Delta and
      Moldova Republic, as well as to 137Cs concentrations from the rest of Europe
      reported by literature. The 137Cs surface concentrations in soil samples ranged
      between 0.4+/-0.1kBqm-2 and 301.1+/-3.0kBqm-2, having an average of 8.3+/-0.2kBqm
      2, with more elevated values in the mountain areas (18.3+/-0.6kBqm-2) compared to
      the hills and plains (2.6+/-0.1kBqm-2). Taking into consideration the cardinal
      regions, the northern and western regions received the least amount of 137Cs
      (2.9+/-0.1kBqm-2), while the southern part received 16.3+/-0.6kBqm-2. Sampling
      points with eastern slope exposure received the highest average (27.8+/-0.5kBqm
      2), while southern, north-western and north-eastern ones received less than 8kBqm
      2. Two hotspots are reported at Iezer-Ighiel (72.7+/-5.9kBqm-2) and Tulghes areas
      (51.5+/-0.6kBqm-2).

PMID- 28494288
TI  - Growth trends of beech and Norway spruce in Switzerland: The role of nitrogen
      deposition, ozone, mineral nutrition and climate.
AB  - Understanding the effects of nitrogen deposition, ozone and climate on tree
      growth is important for planning sustainable forest management also in the
      future. The complex interplay of all these factors cannot be covered by
      experiments. Here we use observational data of mature forests for studying
      associations of various biotic and abiotic factors with tree growth. A 30year
      time series on basal area increment of Fagus sylvatica L. and Picea abies Karst.
      in Switzerland was analyzed to evaluate the development in relation to a variety
      of predictors. Basal area increment of Fagus sylvatica has clearly decreased
      during the observation period. For Picea abies no trend was observed. N
      deposition of more than 26 (beech) or 20-22kgNha-1year-1 (Norway spruce) was
      negatively related with basal area increment, in beech stronger than in Norway
      spruce. High N deposition loads and low foliar K concentrations in Fagus were
      correlated with increased drought sensitivity. High air temperatures in winter
      were negatively related with basal area increment in Norway spruce in general and
      in beech at high N:Mg ratio or high N deposition while on an average the relation
      was positive in beech. Fructification in beech was negatively related to basal
      area increment. The increase of fructification observed during the last decades
      contributed thus to the growth decrease. Ozone flux was significantly and
      negatively correlated with basal area increment both in beech and Norway spruce.
      The results show clear non-linear effects of N deposition on stem increment of
      European beech and Norway spruce as well as strong interactions with climate
      which have contributed to the growth decrease in beech and may get more important
      in future. The results not only give suggestions for ecological processes but
      also show the potential of an integral evaluation of observational data.

PMID- 28494289
TI  - Observational evidence of a long-term increase in precipitation due to
      urbanization effects and its implications for sustainable urban living.
AB  - Although projected precipitation increases in East Asia due to future climate
      change have aroused concern, less attention has been paid by the scientific
      community and public to the potential long-term increase in precipitation due to
      rapid urbanization. A ten-year precipitation dataset was analysed for both a
      rapidly urbanized megacity and nearby suburban/rural stations in southern China.
      Rapid urbanization in the megacity was evident from satellite observations. A
      statistically significant, long-term, increasing trend of precipitation existed
      only at the megacity station (45.6mm per decade) and not at the other stations.
      The increase was attributed to thermal and dynamical modifications of the
      tropospheric boundary layer related to urbanization, which was confirmed by the
      results of our WRF-SLUCM simulations. The results also suggested that a long-term
      regional increase in precipitation, caused by greenhouse gas-induced climate
      change, for instance, was not evident within the study period. The urbanization
      induced increase was found to be higher than the precipitation increase (18.3mm
      per decade) expected from future climate change. The direct climate impacts due
      to rapid urbanization is highlighted with strong implications for urban
      sustainable development and the planning of effective adaptation strategies for
      issues such as coastal defenses, mosquito-borne disease spread and heat stress
      mortality.

PMID- 28494290
TI  - Importance of aerosol non-sphericity in estimating aerosol radiative forcing in
      Indo-Gangetic Basin.
AB  - Aerosols are usually presumed spherical in shape while estimating the direct
      radiative forcing (DRF) using observations or in the models. In the Indo-Gangetic
      Basin (IGB), a regional aerosol hotspot where dust is a major aerosol species and
      has been observed to be non-spherical in shape, it is important to test the
      validity of this assumption. We address this issue using measured chemical
      composition at megacity Delhi, a representative site of the western IGB. Based on
      the observation, we choose three non-spherical shapes - spheroid, cylinder and
      chebyshev, and compute their optical properties. Non-spherical dust enhances
      aerosol extinction coefficient (betaext) and single scattering albedo (SSA) at
      visible wavelengths by >0.05km-1 and >0.04 respectively, while it decreases
      asymmetry parameter (g) by ~0.1. Accounting non-sphericity leads top-of-the
      atmosphere (TOA) dust DRF to more cooling due to enhanced backscattering and
      increases surface dimming due to enhanced betaext. Outgoing shortwave flux at TOA
      increases by up to 3.3% for composite aerosols with non-spherical dust externally
      mixed with other spherical species. Our results show that while non-sphericity
      needs to be accounted for, choice of shape may not be important in estimating
      aerosol DRF in the IGB.

PMID- 28494291
TI  - Distribution and sensorial relevance of volatile organic compounds emitted
      throughout wastewater biosolids processing.
AB  - A diverse range of volatile organic compounds (VOCs) are emitted from wastewater
      biosolids processing. Odorous emissions are predominately made up of volatile
      sulfur compounds (VSCs) which are typically the only odorants measured. However,
      a range of VOCs are known to contribute to malodours yet previous studies often
      overlook the contribution of VOCs in comparison with VSCs. This study aims to
      evaluate how emissions are affected by different biosolids processing
      configurations, and if any non-sulfur VOCs should be included in odour
      measurement and management. Non-sulfur VOCs emitted from biosolids throughout six
      wastewater treatment plants in the Sydney, Australia region were measured at six
      locations on average twice each week over 2-3weeks at each site. Variations in
      types of VOCs emitted throughout and between the sites were assigned to
      differences in WWTP processing configurations, plant operation and variations in
      industrial and municipal flows to the sewer network, referred to as sewer
      catchments. The presence of VOCs is likely due to biotic generation as well as
      industrial or residential additions to the sewer network. The dewatered and
      stored biosolids samples had the highest levels of VOC emissions. Sensorially
      important odorants were p-cresol and butanoic acid, based on the frequency of
      detection and odour activity values. Other compounds with a high risk of nuisance
      impacts were trimethylamine, indole and phenol emitted from the dewatered and
      stored biosolids, and volatile fatty acids from the anaerobic digester inlet and
      outlet at one particular site. The findings show that non-sulfur VOCs should be
      added to odorant monitoring campaigns at WWTPs. Identification of VOCs as
      sensorially important odorants opens opportunities for the more efficient
      management of nuisance odours, through targeted odour control or process
      improvement.

PMID- 28494292
TI  - Trace element levels in an area impacted by old mining operations and their
      relationship with beehive products.
AB  - The environmental status of an area impacted by Roman mining activities was
      assessed in order to establish the current risks posed by such old mine
      emplacements. For this purpose, soil samples were collected throughout the mining
      area and analysed for their total, mobile and mobilizable trace element (As, Cd,
      Mo, Sb and Zn) contents. Additionally, beehive products (honey and pollen) were
      also sampled and evaluated for their use as environmental indicators of the area.
      The results obtained were compared with those from a control non-polluted area.
      The mine soils presented slightly increased levels of Cd and Sb (about 2- to -3
      fold their normal soil concentrations), whereas the enrichment of As reached
      considerable levels, with concentrations almost ten-fold of those considered the
      threshold for causing toxicity. Leachable As contents exhibited very high values
      (1.2-21.9mgkg-1), indicating the need for risk attenuation measures. All trace
      elements were mainly partitioned in the soil residual fraction, especially Mo (76
      99%) and Sb (61-91%). Significant partitioning levels were also found in the
      reducible fraction of As (up to 35%) and Cd (up to 38%), and in the oxidizable
      fraction of Mo (up to 23%). The reducible pool of As was particularly relevant
      due to the eventual mobilization of this element under reducing conditions. Among
      the beehive products tested, honey proved not to be useful as an environmental
      indicator, whereas pollen showed great potential as an indicator when the
      contamination levels were moderate to high.

PMID- 28494293
TI  - Fate of arsenic before and after chemical-enhanced washing of an arsenic
      containing soil in Hong Kong.
AB  - This study evaluated the feasibility of 2-h chemical-enhanced washing of As
      containing soil resulting from geogenic sources in Hong Kong and the fate of As
      before and after remediation. The soil morphology and As speciation in soil was
      elucidated by scanning electron microscopy with energy dispersive X-ray
      spectroscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, and X-ray
      absorption spectroscopy. Integrated analysis of the results suggests that the As
      (>90%) resides predominantly as arsenate bound to ferric iron oxides, with a
      minor contribution (<10%) from an AsIII-sulphide phase. This accounts for the
      marginal leachability, mobility, and bioaccessibility of geogenic As in the
      untreated soil despite its high concentration. Among the five types of reagents
      (organic ligands, reductants, alkaline solvents, inorganic acids, and chelants),
      only dithionite-citrate-bicarbonate method and alkaline solvents (NaOH and
      Na2CO3) extracted 37-78% and 26-42% of the As by mineral dissolution. However,
      these extraction methods notably increased the leachability, mobility, and
      bioaccessibility of remaining As after soil washing, suggesting that a
      significant proportion of newly released As is prone to re-adsorption onto the
      soil surface and becomes highly mobile and bioaccessible. While inorganic acids
      and chelating agents had marginal effects on the fate of remaining As, organic
      ligands (citrate, oxalate, or pyrophosphate) probably destabilized the bonding of
      geogenic As and increased its mobility/bioaccessibility despite marginal
      extraction. The applicability of chemical extraction of geogenic As is
      questionable regardless of chemical agents, thus proper management of the As
      containing soil by containment or physical encapsulation may be considered before
      land development.

PMID- 28494294
TI  - Quantifying the impact of climate change on crop yield and water footprint of
      rice in the Nam Oon Irrigation Project, Thailand.
AB  - Northeast Thailand makes a significant contribution to fragrant and high-quality
      rice consumed within Thailand and exported to other countries. The majority of
      rice is produced in rainfed conditions while irrigation water is supplied to rice
      growers in the dry season. This paper quantifies the potential impact of climate
      change on the water footprint of rice production using the DSSAT (CERES-Rice)
      crop growth model for the Nam Oon Irrigation Project located in Northeast
      Thailand. Crop phenology data was obtained from field experiments and used to set
      up and validate the CERES-Rice model. The present and future water footprint of
      rice, the amount of water evaporated during the growing period, was calculated
      under current and future climatic condition for the irrigation project area. The
      outputs of three regional climate models (ACCESS-CSIRO-CCAM, CNRM-CM5-CSIRO-CCAM,
      and MPI-ESM-LR-CSIRO-CCAM) for scenarios RCP 4.5 and RCP 8.5 were downscaled
      using quantile mapping method. Simulation results show a considerably high
      increase in the water footprint of KDML-105 and RD-6 rice varieties ranging from
      56.5 to 92.2% and 27.5 to 29.7%. respectively for the future period under RCP
      4.5, and 71.4 to 76.5% and 27.9 to 37.6%, respectively under RCP 8.5 relative to
      the simulated baseline water footprint for the period 1976-2005. Conversely, the
      ChaiNat-1 variety shows a decrease in projected water footprint of 42.1 to 39.4%
      under RCP 4.5 and 38.5 to 31.7% under RCP 8.5. The results also indicate a huge
      increase in the future blue water footprint, which will consequently cause a high
      increment in the irrigation water requirement in order to meet the plant's
      evaporation demand. The research outcome highlights the importance of proper
      adaptation strategies to reduce or maintain acceptable water footprints under
      future climate conditions.

PMID- 28494295
TI  - Using a multi-criteria analysis to identify rivers with hydromorphological
      restoration priority: Braided rivers in the south-eastern Subcarpathians
      (Romania).
AB  - In order to systematically plan river restoration actions at a regional scale,
      this paper develops a multi-criteria analysis that classifies rivers, based on
      their priority for hydromorphological restoration. This priority is defined by
      severe human pressures within the erodible corridor of the river, drastic
      alteration of the stream channel, and low intensity of river pattern functioning.
      Based on relevant indicators for three groups of features (human pressures,
      channel changes, and river functionality), a Hydromorphological Restoration
      Priority Index (HRPI) was designed. The high values (>66%) of HRPI reflect an
      urgent need for hydromorphological restoration while low values (<33%) reveal a
      less immediate necessity for restoration. The proposed methodology was applied on
      braided sectors of rivers crossing the south-eastern (Curvature) Subcarpathians
      (Romania). The values of the total HRPI ranged between 21% (Zabraut River) and
      almost 44% (Prahova River). According to our results, most of the analyzed
      sectors have a low need for hydromorphological restoration of the braided
      pattern, while some have a moderate necessity for restoration. Whereas the
      Prahova River has the highest HRPI, it should be given priority for restoration
      at a regional scale, which corresponds to the objectives of River Basin
      Management Plans for the interval beyond 2021.

PMID- 28494297
TI  - Episodic acidification of 5 rivers in Canada's oil sands during snowmelt: A 25
      year record.
AB  - Episodic acidification during snowmelt is a natural phenomenon that can be
      intensified by acidic deposition from heavy industry. In Canada's oil sands
      region, acid deposition is estimated to be as much as 5% of the Canadian total
      and large tracks of northeastern Alberta are considered acid-sensitive because of
      extensive peatland habitats with poorly weathered soils. To identify the
      frequency, duration and severity of acidification episodes during snowmelt (the
      predominant hydrological period for delivery of priority pollutants from
      atmospheric oil sands emissions to surface waters), a 25-year record (1989 to
      2014) of automated water quality data (pH, temperature, conductivity) was
      assembled for 3 rivers along with a shorter record (2012-2014) for another 2
      rivers. Acidic episodes (pH<7, ANC<0) were recorded during 39% of all 83 snowmelt
      events. The severity (duration x magnitude) of episodic acidification increased
      exponentially over the study period (r2=0.56, P<0.01) and was strongly correlated
      (P<0.01) with increasing maximum air temperature and weakly correlated with
      regional land development (P=0.06). Concentrations of aluminum and 11 priority
      pollutants (Sb, As, Be, Cd, Cr, Cu, Pb, Se, Ag, Tl and Zn) were greatest (P<0.01)
      during low (<6.5) pH episodes, particularly when coincident with high discharge,
      such that aluminum and copper concentrations were at times high enough to pose a
      risk to juvenile rainbow trout (Oncorhynchus mykiss). Although low pH (pH<6.5)
      was observed during only 8% of 32 acidification episodes, when present, low pH
      typically lasted 10days. Episodic surface water acidification during snowmelt,
      and its potential effects on aquatic biota, is therefore an important
      consideration in the design of long-term monitoring of these typically alkaline
      (pH=7.72+/-0.05) rivers.

PMID- 28494296
TI  - Quantification of ozone exposure- and stomatal uptake-yield response
      relationships for soybean in Northeast China.
AB  - High ground-level O3 is a new threat to agricultural production in Northeast
      China with the increasing ambient O3 concentration. Little is known about its
      impacts on soybean production in this key agricultural region. Accumulated O3
      exposure-response and stomatal O3 flux-response relationships were developed
      during two continuous growing seasons to evaluate O3-induced yield reduction of
      four typical soybean cultivars in Northeast China. Results showed that critical
      levels of AOT40 (accumulated hourly O3 concentrations over a threshold of
      40nmol.mol-1), SUM06 (sum of all hourly average O3 concentrations over
      0.06MUmol.mol-1) and W126 (sum of O3 concentrations weighted by a sigmoidal
      function) in relation to 5% reduction in relative seed yield were 4.2, 7.6 and
      6.8MUmol.mol-1.h, respectively. The effect of O3 on plants was influenced by leaf
      position in canopy. An improved Jarvis stomatal conductance model including leaf
      (node) position fitted well with field measurements. The best linear relationship
      between stomatal O3 flux and relative soybean yield was obtained when phytotoxic
      ozone dose was integrated over a threshold of 9.6nmol.m-2.s-1 (POD9.6) to
      represent the detoxification capacity of soybean. POD9.6 and the commonly used
      POD6 in relation to 5% reduction in relative seed yield of soybean were 0.9mmol.m
      2 and 1.8mmol.m-2, respectively. O3 concentrations above ~38nmol.mol-1
      contributed to POD9.6 and caused seed yield loss in soybean. Current annual yield
      loss of soybean at ambient O3 was estimated to range between 23.4% and 30.2%. The
      O3 dose-response relationships and corresponding thresholds obtained here will
      benefit regional O3 risk assessment on soybean production in Northeast China.

PMID- 28494298
TI  - Remediation of PAH polluted soils using a soil microbial fuel cell: Influence of
      electrode interval and role of microbial community.
AB  - The soil microbial fuel cells (SMFCs) were constructed to remediate soils
      contaminated by polycyclic aromatic hydrocarbons (PAHs). With a maximum power
      density of 12.1mWm-2 and an internal resistance of 470Omega, a closed SMFC showed
      electricity generation comparable to that by an open SMFC after 175days of
      operation and meanwhile increased the removal rates of anthracene, phenanthrene,
      and pyrene to 54.2+/-2.7%, 42.6+/-1.9% and 27.0+/-2.1% from 20.8+/-1.1%, 17.3+/
      1.2% and 11.7+/-0.9%, respectively, by the open SMFC. Both the electricity
      generation and the removal of PAHs increased with the decreased electrode
      interval. When the electrode interval ranged between 4cm and 10cm, the more
      closely the electrodes were positioned, the more efficient the electricity
      generation and removal of PAHs became. Dominated by the genus of Geobacter, the
      SMFC was enriched in electrogenic bacteria at the anode surface, and the growth
      of certain microbes other than electrogenic bacteria in the soil was improved by
      electrical stimulation. This finding reveals the critical mechanism underlying
      electricity generation and improved the removal of PAHs.

PMID- 28494299
TI  - Mycorrhization protects Betula pubescens Ehr. from metal-induced oxidative stress
      increasing its tolerance to grow in an industrial polluted soil.
AB  - In recent years, the use of woody plants in phytoremediation has gained
      popularity due to their high biomass production and their association with
      mycorrhizal fungi, which can improve their survival and development rates under
      stress conditions. In this study, mycorrhized and non-mycorrhized white birch
      plants (Betula pubescens Ehr.) were grown in control and a metal-polluted
      industrial soil. After 60days of culture, plant growth and metal accumulation,
      the content of photosynthetic pigments and oxidative-stress markers, as well as
      the enzymatic activities and gene expressions of antioxidant enzymes were
      measured. According to our results, mycorrhized birch plants grown in control
      soil showed an increased activity and gene expression of catalase and ascorbate
      peroxidase, along with hydrogen peroxide overproduction, which could support the
      importance of the reactive oxygen species as signaling molecules in the
      regulation of plant-fungus interactions. Additionally, in polluted soil
      mycorrhized plants had higher biomass but lower metal accumulation, probably
      because the symbiotic fungus acted as a barrier to the entrance of metals into
      the host plants. This behavior led to mitigation in the oxidative challenge,
      reduced hydrogen peroxide content and diminished activities of the antioxidant
      enzymes in comparison to non-mycorrhized plants.

PMID- 28494300
TI  - Behaviour of the main nonsteroidal anti-inflammatory drugs in a membrane
      bioreactor treating urban wastewater at high hydraulic- and sludge-retention
      time.
AB  - The behaviour and removal efficiency of ibuprofen (IBU), diclofenac (DCF),
      ketoprofen (KPF), and naproxen (NPX) during the real urban wastewater treatment
      by an experimental full-scale MBR working at high sludge and hydraulic retention
      time (SRT, HRT) were determined. The MBR worked in denitrification/nitrification
      conformation at 35.4h of HRT (Q=0.45m3/h), 37 d of SRT and a recirculation flow
      rate of 4Q. The experiments were made under steady-state conditions, reaching a
      biodegradable organic matter removal higher than 99.5%. The MBR system showed
      similar removal capacity for IBU, NPX, and KTP (>95%), whose main transformation
      occurred in the aerobic reactor with a low contribution from the anoxic reactor.
      The system worked with complete nitrification, also achieving an effective
      retention of the unbiodegradable organic matter due to recirculation. DCF removal
      was low with negative removal yields for several samplings. Both removal and
      increase transformation of DCF also occurred in the aerobic reactor, this not
      being observed in the anoxic one. DCF tends to accumulate in the system and to be
      recirculated. Thus, during the sampling in which DCF influent concentration
      decreases, removal yields turn negative. The increase of DCF concentration in the
      aerobic bioreactor also contributes to the negative removal yields.

PMID- 28494301
TI  - Transformation of hazardous lead into lead ferrite ceramics: Crystal structures
      and their role in lead leaching.
AB  - This study quantitatively determined the transformation of lead into lead ferrite
      ceramics and examined the influence of structural defects in lead ferrites (i.e.
      Pb2Fe2O5, PbFe4O7 and PbFe12O19) on lead leaching. Mechanisms of metal
      incorporation were examined from quantifying the phase compositions of lead
      ferrites in the products of sintering lead oxide with hematite. At low
      temperature of 700 degrees C, Pb was preferentially incorporated into the
      Pb2Fe2O5 crystals, and the incorporation efficiency ranged from 25.7 to 97.5%
      depending on different Pb/Fe molar ratios. By increasing temperatures to 750-850
      degrees C, Pb2Fe2O5 was subsequently reacted with hematite for the formation of
      PbFe4O7 and PbFe12O19 in Pb/Fe of 1/4 and 1/12 systems. PbFe12O19 was found to be
      the high-temperature (1000 degrees C) stable phase for incorporating lead, and
      the incorporation efficiency ranged from 28.6 to 92.1% by different Pb/Fe molar
      ratios. Leaching tests demonstrated that PbFe12O19 was more resistant to acid
      attack than Pb2Fe2O5 and PbFe4O7. The crystal structural defects in Pb2Fe2O5 and
      PbFe4O7 were determined to be the factors influencing their intrinsic phase
      durability. On the other hand, PbFe12O19 was relatively free of structural
      defects and was found to be the preferred stabilization product to reduce the
      environmental hazard posed by lead.

PMID- 28494302
TI  - Super high removal capacities of heavy metals (Pb2+ and Cu2+) using CNT
      dendrimer.
AB  - This research demonstrates the capability of carbon nanotubes (CNT) modified with
      four generations of poly-amidoamine dendrimer (PAMAM, G4) to remove Cu2+ and Pb2+
      heavy metals from aqueous solution in single and binary component systems.
      Uniquely high adsorption capacities for copper and lead, which are 3333 and
      4870mg/g respectively, were achieved. FTIR, H1 NMR, Zeta potential, SEM and TEM
      techniques were employed for characterizing the synthetic nanocomposite and
      indicated that the dendrimer functionalized CNTs have been synthesized. The
      effects of several parameters including initial metal ion concentration, solution
      pH and the nanocomposite dosage were studied. The experimental data were analyzed
      by the Langmuir and Freundlich isotherms and the pseudo-first order and pseudo
      second order kinetics models. The maximum adsorption occurred at pH=7. The
      adsorption process for Cu2+ and Pb2+ in single and binary component systems fit
      the Langmuir and extended Langmuir models respectively. This study also tested
      the kinetic sorption of the metals on PAMAM/CNT in single and binary component
      metal systems at various metal ions concentrations. The results showed that
      PAMAM/CNT nanocomposite was a super-adsorbent, able to uptake uniquely large
      quantities of heavy metal from single and binary component liquid phase.

PMID- 28494303
TI  - Hemocompatibility of inhaled environmental nanoparticles: Potential use of in
      vitro testing.
AB  - Hemocompatibility testing is an important part in the evaluation of nano-based
      medicines. However, it is not systematically used for the assessment of
      environmental particles since they do not come in contact with blood immediately.
      Studies on human exposure to air-borne particles and pulmonary exposure of
      rodents have reported alterations in blood physiology. It is not clear, whether
      these effects are majorly caused by tissue inflammation or translocated particles
      in blood. This review addresses the question, if in vitro hemocompatibility
      testing could help in the risk evaluation of inhaled particles. Particle blood
      concentrations were estimated based on exposure levels, ventilation volume,
      deposition rate, lung surface area, and permeability of the alveolar epithelium
      to particles. The categories of hemocompatibility, thrombosis, coagulation,
      platelets, hematology, and immunology, were introduced. Also, concentrations of
      ultrafine particles, silver nanoparticles, carbon nanotubes that caused adverse
      effects in human blood samples were compared to the estimated concentrations of
      translocated particles. The comparison suggested that, it is unlikely for
      translocated nanoparticles to be the sole cause of adverse blood effects.
      Nevertheless, the testing of specific hemocompatibility parameters (hemolysis and
      clotting) in healthy blood might help to compare biological effect of inhaled
      particles containing different amounts of contamination. Testing of samples from
      healthy and diseased persons might help to identify pathological dispositions
      that increase the possibility of adverse reaction of nanoparticles in blood.

PMID- 28494304
TI  - Successful sulfur recovery in low sulfurate compounds obtained from the zinc
      industry: Evaporation-condensation method.
AB  - The improvement of an evaporation-condensation method allows for successful
      recovery of elemental sulfur from sulfide concentrates from the zinc industry.
      Elemental sulfur can be obtained with this method in samples with a low (60%)
      sulfur content. The effects of heating temperature between 150 degrees C and 250
      degrees C and heating time up to 120min on the recovery of sulfur are also
      studied. Elemental sulfur obtained in this way is of high purity and therefore,
      there is no need for further purification. The treatment of these industrial
      residues would help removing sulfur from the environment.

PMID- 28494306
TI  - Membranes based on polymer miscibility for selective transport and separation of
      metallic ions.
AB  - Polymer inclusion membranes (PIM) used for selective transport and separation of
      metallic ions have emerged in recent times. Their expansion depends on the method
      of preparation and their suitable structure and physico-chemical characteristics.
      In this paper, a novel category of membranes for ions separation is reported. The
      membranes were synthesized by thermally induced phase separation using a mixture
      of polyvinylidene fluoride (PVDF) and cellulose triacetate (CTA) plasticized by
      tris(2-ethylhexyl) phosphate (TEHP) and with di-(2-ethylhexyl) phosphoric acid
      (D2EHPA) incorporated into the polymer as carrier to increase specific
      interactions between polymers. PIM membrane exhibited a hydrophobic (~100 degrees
      ) and thermally stable up to ~200 degrees C porous homogenous structure. The
      transport of Ni(II), Zn(II) and Pb(II) from aqueous solutions was studied by
      competitive transport across polymer inclusion membranes (PIM). Competitive
      transport of ions in solution across PIM provide the selectivity order: Ni2+
      (45%)>Pb2+ (35%)>Zn2+ (5%). A long-term transport experiment was carried out to
      study the durability of the system.

PMID- 28494305
TI  - Photovoltage response of (XZn)Fe2O4-BiFeO3 (X=Mg, Mn or Ni) interfaces for highly
      selective Cr3+, Cd2+, Co2+ and Pb2+ ions detection.
AB  - High-photostability fluorescent (XZn)Fe2O4 (X=Mg, Mn or Ni) embedded in BiFeO3
      spinel-perovskite nanocomposites were successfully fabricated via a novel bio
      induced phase transfer method using shewanella oneidensis MR-1. These
      nanocomposites have the near-infrared fluorescence response (XZn or Fe)-O-O-(Bi)
      interfaces (785/832nm), and the (XZn)Fe2O4/BiFeO3 lattices with high/low
      potentials (572.15-808.77meV/206.43-548.1meV). Our results suggest that heavy
      metal ion (Cr3+, Cd2+, Co2+ and Pb2+) d? orbitals hybridize with the paired-spin
      X-Zn-Fe d?-d?-d?? orbitals to decrease the average polarization angles (-29.78 to
      44.71 degrees ), qualitatively enhancing the photovoltage response selective
      potentials (39.57-487.84meV). The fluorescent kinetic analysis shows that both
      first-order and second-order equilibrium adsorption isotherms are in line and
      meet the Langmuir and Freundlich modes. Highly selective fluorescence detection
      of Co2+, Cr3+ and Cd2+ can be achieved using Fe3O4-BiFeO3 (Langmuir mode),
      (MgZn)Fe2O4-BiFeO3 and (MnZn)Fe2O4-BiFeO3 (Freundlich mode), respectively. Where
      the corresponding max adsorption capacities (qmax) are 1.5-1.94, 35.65 and 43.7
      multiple, respectively, being more competitive than that of other heavy metal
      ions. The present bio-synthesized method might be relevant for high
      photostability fluorescent spinel-perovskite nanocomposites, for design of heavy
      metal ion sensors.

PMID- 28494307
TI  - A resonance Rayleigh scattering sensor for detection of Pb2+ ions via cleavage
      induced G-wire formation.
AB  - A resonance Rayleigh scattering (RRS) aptasensor was fabricated for detection of
      Pb2+via hairpin-like label-free substrate and G-wire for signal amplification. A
      hairpin-like DNA substrate contains a sequence in the loop labeled with
      ribonucleobase A and c-myc sequence in the stem. When hybridized with 8-17
      DNAzyme in the presence of Pb2+, the sequence in the loop was activated and
      cleaved. Hundreds of c-myc sequences departing from the 8-17 DNAzyme yield
      nanowires superstructure called G-wire in the presence of Mg2+. The polymer G
      wire was demonstrated by the RRS spectrum, polyacrylamide gel electrophoresis,
      and AFM. The RRS intensity was enhanced by the product G-wires, and the RRS
      signal at 370nm was linear with the logarithm of Pb2+ concentration in the range
      of 2.0nM to 5.0MUM. This method was selective for Pb2+ even coexisting with other
      metal ions at high concentrations and was successfully applied to the
      determination of Pb2+ in real samples. The aptasensor holds a great promise for
      universal RRS sensing platform for sensitive detection of various metal ions just
      by changing the sequence of the probe in the loop and DNAzyme.

PMID- 28494308
TI  - Unravelling cadmium toxicity and nitric oxide induced tolerance in Cucumis
      sativus: Insight into regulatory mechanisms using proteomics.
AB  - Nitric oxide (NO) is a signal molecule that can mediate a wide range of
      physiological processes against cadmium (Cd) toxicity in plants. However, little
      information can be used to reveal the global and systematic mitigative mechanism
      of NO in improving Cd stress tolerance of cucumber plants. In the present study,
      we used Isobaric Tag for Relative and Absolute Quantification (iTRAQ) analysis to
      identify 1691 proteins, which can be used to determine the role of NO in
      regulating the molecular changes of proteome in cucumber leaves exposed to Cd
      stress. Several dysregulated key proteins indicated that Cd-induced physiological
      deterioration of cucumber leaves were mainly involved in metabolic process,
      cellular process, response to stimulus and so on. Metabolic pathway analysis
      indicated that several Cd-disruptive pathways were markedly reversed by NO
      treatments, including Cd transport and localization, photosynthesis, chlorophyll
      metabolism, redox homeostasis, glutathione-mediated Cd detoxification and Ca2+
      signaling transduction. Taken together, this iTRAQ analysis provides more
      comprehensive insights into the physiological and molecular mechanisms of NO
      against Cd toxicity in cucumber plants.

PMID- 28494309
TI  - Macroscopic and spectroscopic studies of the enhanced scavenging of Cr(VI) and
      Se(VI) from water by titanate nanotube anchored nanoscale zero-valent iron.
AB  - Herein, a promising titanate nanotubes (TNT) anchored nanoscale zero-valent iron
      (NZVI) nanocomposite (NZVI/TNT) was synthesized, characterized and used for the
      enhanced scavenging of Cr(VI) and Se(VI) from water. The structural
      identification indicated that NZVI was uniformly loaded on TNT, thereby, the
      oxidation and aggregation of NZVI was significantly minimized. The macroscopic
      experimental results indicated that NZVI/TNT exhibited higher efficiency as well
      as rate on Cr(VI) and Se(VI) scavenging resulted from the good synergistic effect
      between adsorption and reduction. Besides, TNT can weaken the inhibitory effect
      of co-existing humic acid (HA) and fulvic acid (FA) on the scavenging of Cr(VI)
      and Se(VI) by NZVI, since TNT showed strong adsorption for HA and FA that inhibit
      potential reactivity. XPS analysis suggested that surface-bound Fe(II) played a
      critical role in Cr(VI) and Se(VI) scavenging. XANES analysis demonstrated that
      TNT acted as a promoter for the almost complete transformation of Cr(VI) into
      Cr(III), and Se(VI) into Se(0)/Se(-II) in NZVI system. EXAFS analysis indicated
      that TNT acted as a scavenger for insoluble products, and thus more reactive
      sites can be used for Cr(VI) and Se(VI) reduction. The excellent performance of
      NZVI/TNT provide a potential material for purification and detoxification of
      Cr(VI) and Se(VI) from wastewater.

PMID- 28494310
TI  - A novel and facile strategy for highly flame retardant polymer foam composite
      materials: Transforming silicone resin coating into silica self-extinguishing
      layer.
AB  - In this study, a novel strategy was developed to fabricate highly flame retardant
      polymer foam composite materials coated by synthesized silicone resin (SiR)
      polymer via a facile dip-coating processing. Applying the SiR polymer coating,
      the mechanical property and thermal stability of SiR-coated polymer foam (PSiR)
      composites are greatly enhanced without significantly altering their structure
      and morphology. The minimum oxygen concentration to support the combustion of
      foam materials is greatly increased, i.e. from LOI 14.6% for pure foam to LOI 26
      29% for the PSiR composites studied. Especially, adjusting pendant group to SiOSi
      group ratio (R/Si ratio) of SiRs produces highly flame retardant PSiR composites
      with low smoke toxicity. Cone calorimetry results demonstrate that 44-68%
      reduction in the peak heat release rate for the PSiR composites containing
      different R/Si ratios over pure foam is achieved by the presence of appropriate
      SiR coating. Digital and SEM images of post-burn chars indicate that the SiR
      polymer coating can be transformed into silica self-extinguishing porous layer as
      effective inorganic barrier effect, thus preserving the polymer foam structure
      from fire. Our results show that the SiR dip-coating technique is a promising
      strategy for producing flame retardant polymer foam composite materials with
      improved mechanical properties.

PMID- 28494311
TI  - Bromination of petroleum coke for elemental mercury capture.
AB  - Activated carbon injection has been proven to be an effective control technology
      of mercury emission from coal-fired power plants. Petroleum coke is a waste by
      product of petroleum refining with large quantities readily available around the
      world. Due to its high inherent sulfur content, petroleum coke is an attractive
      raw material for developing mercury capture sorbent, converting a waste material
      to a value-added product of important environmental applications. In this study,
      petroleum coke was brominated by chemical-mechanical bromination. The brominated
      petroleum coke was characterized for thermal stability, mercury capture capacity,
      and potential mercury and bromine leaching hazards. Bromine loaded on the
      petroleum coke was found to be stable up to 200 degrees C. Even after treating
      the brominated petroleum coke for 30min at 600 degrees C, 1/3 bromine remained on
      the solid. The sorbent from bromination of sulfur-containing petroleum coke was
      shown to be a promising alternative to commercial brominated activated carbon for
      capture of elemental mercury from coal combustion flue gases.

PMID- 28494312
TI  - Anagyrine desensitization of peripheral nicotinic acetylcholine receptors. A
      potential biomarker of quinolizidine alkaloid teratogenesis in cattle.
AB  - Anagyrine, a teratogenic quinolizidine alkaloid found in Lupinus spp., is
      proposed to undergo metabolism by pregnant cattle to a piperidine alkaloid which
      inhibits fetal movement, the putative mechanism behind crooked calf syndrome. The
      objective of this study was to test the hypothesis that anagyrine but not
      lupanine or sparteine can directly, without metabolism, desensitize nicotinic
      acetylcholine receptors (nAChR) in a cell culture model. SH-SY5Y cells expressing
      autonomic nAChR, and TE-671 cells expressing fetal muscle-type nAChR were exposed
      to lupine alkaloids or Dimethylphenylpiperazinium (DMPP) in log10 molar
      increments from 10nM to 100MUM and then to a fixed concentration of acetylcholine
      (ACh) (10MUM for SH-SY5Y cells and 1MUM for TE-671 cells) and the responses
      measured with a membrane potential sensing dye to assess nAChR activation and
      desensitization. The selective ganglionic nAChR agonist DMPP used as a positive
      control, was a potent activator and desensitizer of nAChR expressed by SH-SY5Y
      cells. Lupanine was a weak agonist and desensitizer in SH-SY5Y cells and
      sparteine was without effect. Anagyrine acted as a partial agonist in both cell
      lines with EC50 values of 4.2 and 231MUM in SH-SY5Y and TE-671 cells,
      respectively. Anagyrine was a desensitizer of nAChR with DC50 values of 6.9 and
      139MUM in SH-SY5Y and TE-671 cells, respectively. These results confirm the
      hypothesis that anagyrine is a potent and effective desensitizer of nAChR, and
      that anagyrine can directly, without metabolism, desensitize nAChR. Moreover,
      serum anagyrine concentrations may be a potential biomarker for lupine
      teratogenicity in cattle.

PMID- 28494313
TI  - Heavy metals translocation and accumulation from the rhizosphere soils to the
      edible parts of the medicinal plant Fengdan (Paeonia ostii) grown on a metal
      mining area, China.
AB  - Fengdan (Paeonia ostii) is one of Chinese 34 famous medicinal materials. This
      study investigated the concentrations of Arsenic (As), Chromium (Cr), Cadmium
      (Cd), Copper (Cu), Lead (Pb), Iron (Fe), Manganese (Mn), and Zinc (Zn) in
      rhizosphere soils, cortex mouton and seeds of Fengdan planted in a metal mining
      area, China. The mean concentrations of As, Cd, Cu, and Zn in the rhizosphere
      soils were above the limits set by the Chinese Soil Environmental Quality
      Standard (GB 15618-1995). The contamination factor (CF) of Cd was >5, while it
      was >2for As, Cu, Pb, and Zn in all the soils. The integrated pollution index for
      all the soils was >3 and ? 5. Metal concentrations in the edible parts of Fengdan
      were in the following decreasing order: Mn>Fe>Zn>Cu>Pb>As>Cr>=Cd. The transfer
      factor mean values for As, Cu, Cd and Fe in the cortex moutan of old Fengdan
      (over 6 years) were significantly higher than in young Fengdan. Available metal
      concentrations, pH and soil organic matter content influenced the metal
      concentrations of the cortex moutan. The results indicated that mining and
      smelting operations have led to heavy metals contamination of soils and medicinal
      parts of Fengdan. The major metal pollutants were elemental Cd, Cu, Pb, and Zn.
      Heavy metals mainly accumulated in the cortex moutan of Fengdan. The mean
      concentrations of Cd, Cu, and Pb in the old cortex moutan (over 6 years) were
      above those of the Chinese Green Trade Standards for Medicinal Plants and
      Preparations in Foreign Trade (WM/T2-2004).

PMID- 28494314
TI  - Structure and gene cluster of the O-antigen of Escherichia albertii O1 resembling
      the O-antigen of Pseudomonas aeruginosa O5.
AB  - The O-specific polysaccharide (O-antigen) was obtained by mild acid degradation
      of the lipopolysaccharide of Escherichia albertii serotype O1 strain SP20140089
      and studied by sugar analysis along with 1D and 2D 1H and 13C NMR spectroscopy.
      The following structure was established for the trisaccharide repeating unit of
      the O-polysaccharide: ->4)-beta-d-ManpNAc3NAcA-(1 -> 4)-beta-d-GlcpNAm3NAcA-(1 ->
      3)-alpha-d-GlcpNAc-(1-> where ManNAc3NAcA and GlcNAm3NAcA indicate 2,3
      diacetamido-2,3-dideoxymannuronic acid and 2-acetimidoylamino-3-acetamido-2,3
      dideoxyglucuronic acid, respectively. While showing some similarity with O
      polysaccharide structures of a group of Pseudomonas aeruginosa serotypes (O2, O5,
      O16, O18, and O20), that of E. albertii O1 is unique among known bacterial
      polysaccharide structures. The gene cluster for biosynthesis of the O1-antigen
      was sequenced and functions of the genes were predicted by comparison with
      sequences in the available databases, including those involved in the synthesis
      of nucleotide precursors of 2,3-diamino-2,3-dideoxyhexuronic acid derivatives in
      P. aeruginosa O5.

PMID- 28494315
TI  - Glycoengineering and glycosite-specific labeling of serum IgGs from various
      species.
AB  - Chemoenzymatic glycoengineering of immunoglobulin G (IgG) catalyzed by Endo-S is
      a powerful approach to remodel the heterogeneous N-glycoforms of Fc domain with a
      homogeneous synthetic glycan structure for enhanced Fc receptor-mediated effector
      functions. The previous researches on the method development mainly focused on
      human or humanized IgGs with therapeutic potentials. Here, for the first time we
      report the extended application of this method on glycan-remodeling of serum IgGs
      from other species including rabbit, mouse, and goat. Harnessing an azido-tagged
      non-natural N-glycan substrate and successive click reaction, glycosite-specific
      fluorescent labeling of IgGs was enabled. This study provided a new avenue for
      glycoengineering and Fc-specific labeling of IgGs with minimized influence on
      antigen-binding domains, and this method was adaptive to thousands of commercial
      antibody reagents from various species with great application potentials.

PMID- 28494316
TI  - Combinatorial chemistry in drug discovery.
AB  - Several combinatorial methods have been developed to create focused or diverse
      chemical libraries with a wide range of linear or macrocyclic chemical molecules:
      peptides, non-peptide oligomers, peptidomimetics, small-molecules, and natural
      product-like organic molecules. Each combinatorial approach has its own unique
      high-throughput screening and encoding strategy. In this article, we provide a
      brief overview of combinatorial chemistry in drug discovery with emphasis on
      recently developed new technologies for design, synthesis, screening and decoding
      of combinatorial library. Examples of successful application of combinatorial
      chemistry in hit discovery and lead optimization are given. The limitations and
      strengths of combinatorial chemistry are also briefly discussed. We are now in a
      better position to truly leverage the power of combinatorial technologies for the
      discovery and development of next-generation drugs.

PMID- 28494317
TI  - Consumer evaluations of processed meat products reformulated to be healthier - A
      conjoint analysis study.
AB  - Recent innovations in processed meats focus on healthier reformulations through
      reducing negative constituents and/or adding health beneficial ingredients. This
      study explored the influence of base meat product (ham, sausages, beef burger),
      salt and/or fat content (reduced or not), healthy ingredients (omega 3, vitamin
      E, none), and price (average or higher than average) on consumers' purchase
      intention and quality judgement of processed meats. A survey (n=481) using
      conjoint methodology and cluster analysis was conducted. Price and base meat
      product were most important for consumers' purchase intention, followed by
      healthy ingredient and salt and/or fat content. In reformulation, consumers had a
      preference for ham and sausages over beef burgers, and for reduced salt and/or
      fat over non reduction. In relation to healthy ingredients, omega 3 was preferred
      over none, and vitamin E was least preferred. Healthier reformulations improved
      the perceived healthiness of processed meats. Cluster analyses identified three
      consumer segments with different product preferences.

PMID- 28494318
TI  - Moving beyond description: Closing the health equity gap by redressing racism
      impacting Indigenous populations.

PMID- 28494319
TI  - No baby booms or birth sex ratio changes following Fifty Shades of Grey in the
      United States.
AB  - INTRODUCTION: The Fifty Shades of Grey (FSOG) trilogy were publicised by the
      media as inflaming increased coital activity, and that this would result a baby
      boom. Furthermore, increased coital activity skews the sex ratio at birth (M/T)
      toward male births. This study was carried out in order to ascertain whether
      there were any spikes in total births or in M/T in the United States (US) circa
      nine months following the FSOG books. METHODS: Monthly male and female births for
      the US were obtained directly from the website of the Centre for Disease Control
      (01/2007-12/2015). RESULTS: This study analysed 36,499,163 live births (M/T
      0.5117, 95% CI 0.5116-0.5119). There are no discernible spikes in total births or
      M/T at annual level, or circa nine months after FSOG book releases i.e. 04/2012
      and 01/2013. DISCUSSION: The absence of spikes in births or M/T may have been due
      to exaggeration of the FSOG effect, it may only have provoked planned
      pregnancies, or modern contraception was sufficiently effective to prevent extra
      conceptions. The media build-up may also have stimulated a Hawthorne effect, with
      FSOG-affected individuals employing effective contraception. This study
      highlights the importance of measurement of cause and effect since anticipated
      results may not always ensue from events.

PMID- 28494320
TI  - Can segmental model reductions quantify whole-body balance accurately during
      dynamic activities?
AB  - When investigating whole-body balance in dynamic tasks, adequately tracking the
      whole-body centre of mass (CoM) or derivatives such as the extrapolated centre of
      mass (XCoM) can be crucial but add considerable measurement efforts. The aim of
      this study was to investigate whether reduced kinematic models can still provide
      adequate CoM and XCoM representations during dynamic sporting tasks. Seventeen
      healthy recreationally active subjects (14 males and 3 females; age, 24.9+/
      3.2years; height, 177.3+/-6.9cm; body mass 72.6+/-7.0kg) participated in this
      study. Participants completed three dynamic movements, jumping, kicking, and
      overarm throwing. Marker-based kinematic data were collected with 10
      optoelectronic cameras at 250Hz (Oqus Qualisys, Gothenburg, Sweden). The
      differences between (X)CoM from a full-body model (gold standard) and (X)CoM
      representations based on six selected model reductions were evaluated using a
      Bland-Altman approach. A threshold difference was set at +/-2cm to help the
      reader interpret which model can still provide an acceptable (X)CoM
      representation. Antero-posterior and medio-lateral displacement profiles of the
      CoM representation based on lower limbs, trunk and upper limbs showed strong
      agreement, slightly reduced for lower limbs and trunk only. Representations based
      on lower limbs only showed less strong agreement, particularly for XCoM in
      kicking. Overall, our results provide justification of the use of certain model
      reductions for specific needs, saving measurement effort whilst limiting the
      error of tracking (X)CoM trajectories in the context of whole-body balance
      investigation.

PMID- 28494321
TI  - Objective assessment of movement competence in children using wearable sensors:
      An instrumented version of the TGMD-2 locomotor subtest.
AB  - Movement competence (MC) is defined as the development of sufficient skill to
      assure successful performance in different physical activities. Monitoring
      children MC during maturation is fundamental to detect early minor delays and
      define effective intervention. To this purpose, several MC assessment batteries
      are available. When evaluating movement strategies, with the aim of identifying
      specific skill components that may need improving, widespread MC assessment is
      limited by high time consumption for scoring and the need for trained operators
      to ensure reliability. This work aims to facilitate and support the assessment by
      designing, implementing and validating an instrumented version of the TGMD-2
      locomotor subtest based on Inertial Measurement Units (IMUs) to quantify MC in
      children rapidly and objectively. 45 typically developing children, aged 6-10,
      performed the TGMD-2 locomotor subtest (six skills). During the tests, children
      wore five IMUs mounted on lower back, on ankles and on wrists. Sensor and video
      recordings of the tests were collected. Three expert evaluators performed the
      standard assessment of TGMD-2. Using theoretical and modelling approaches,
      algorithms were implemented to automatically score children tests based on IMUs'
      data. The automatic assessment, compared to the standard one, showed an agreement
      higher than 87% on average on the entire group for each skill and a reduction of
      time for scoring from 15 to 2min per participant. Results support the use of IMUs
      for MC assessment: this approach will allow improving the usability of MC
      assessment, supporting objectively evaluator decisions and reducing time
      requirement for the evaluation of large groups.

PMID- 28494322
TI  - Constituent Lower Extremity Work (CLEW) approach: A novel tool to visualize joint
      and segment work.
AB  - Work can reveal the mechanism by which movements occur. However, work is less
      physically intuitive than more common clinical variables such as joint angles,
      and are scalar quantities which do not have a direction. Therefore, there is a
      need for a clearly reported and comprehensively calculated approach to easily
      visualize and facilitate the interpretation of work variables in a clinical
      setting. We propose the Constituent Lower Extremity Work (CLEW) approach, a
      general methodology to visualize and interpret cyclic tasks performed by the
      lower limbs. Using six degree-of-freedom power calculations, we calculated the
      relative work of the four lower limb constituents (hip, knee, ankle, and distal
      foot). In a single pie chart, the CLEW approach details the mechanical cost-of
      transport, the percentage of positive and negative work performed in stance phase
      and swing phase, and the individual contributions of positive and negative work
      from each constituent. This approach can be used to compare the constituent-level
      adaptations occurring between limbs of individuals with impairments, or within a
      limb at different gait intensities. In this article, we outline how to generate
      and interpret the CLEW pie charts in a clinical report. As an example of the
      utility of the approach, we created a CLEW report using average reference data
      from eight unimpaired adult subjects walking on a treadmill at 0.8 statures/s
      (1.4m/s) compared with data from the intact and prosthetic limbs of an individual
      with a unilateral amputation walking with an above-knee passive prosthesis.

PMID- 28494323
TI  - Stress regulation in drug-resistant epilepsy.
AB  - The prevalence of psychological distress, especially depressive and anxiety
      disorders, is higher in epilepsy than in other chronic health conditions. These
      comorbid conditions contribute even more than epileptic seizures themselves to
      impaired quality of life in patients with epilepsy (PWE). The link between these
      comorbidities and epilepsy appears to have a neurobiological basis, which is at
      least partly mediated by stress through psychological and pathophysiological
      pathways. The impact of stress in PWE is also particularly important because it
      is the most frequently reported seizure trigger. It is therefore crucial for
      clinicians to take stress-related conditions and psychiatric comorbidities into
      account when managing PWE and to propose clinical support to enhance self-control
      of stress. Screening tools have been specially designed and validated in PWE for
      depressive disorders and anxiety disorders (e.g. NDDI-E, GAD-7). Other
      instruments are useful for measuring stress-related variables (e.g. SRRS, PSS,
      SCS, MHLCS, DSR-15, ERP-R, QOLIE-31) in order to help characterize the individual
      "stress profile" and thus orientate patients towards the most appropriate
      treatment. Management includes both pharmacological treatment and
      nonpharmacological methods for enhancing self-management of stress (e.g.
      mindfulness-based therapies, yoga, cognitive-behavioral therapies, biofeedback),
      which may not only protect against psychiatric comorbidities but also reduce
      seizure frequency.

PMID- 28494324
TI  - An unexpected diagnosis of primary omental endometrial stromal sarcoma in a
      patient with acute right abdominal pain: A case report and review of literature.
AB  - INTRODUCTION: Extrauterine Endometrial Stromal Sarcoma (EESS) is an extremely
      rare mesenchymal tumour that simulates other pathologies, and therefore poses a
      diagnostic challenge. This report outlines a case of EESS arising from the
      greater omentum mimicking a colonic tumour, with review of literature.
      PRESENTATION OF CASE: A 47-year-old woman, with history of hysterectomy for
      menorrhagia and hormone replacement therapy (HRT), presented with right sided
      abdominal pain and localized peritonism. On exploratory laparoscopy an omental
      tumour, suspected to arise from the transverse colon was identified and biopsied.
      The histological features suggested an EESS. Colonoscopy ruled out colonic
      lesion. A laparoscopic tumour resection and bilateral salpingo-oophorectomy (BSO)
      was performed. Immunohistochemistry confirmed the diagnosis. No additional
      lesions or associated endometriosis were found. Resection was followed by
      adjuvant medroxyprogesterone-acetate therapy. DISCUSSION: We reviewed 20 cases of
      EESS originating from extragenital abdominopelvic organs reported since 1990.
      Acute presentation is rare, as well as upper abdominal occurrence. Isolated
      omental involvement was previously reported in only one case. Endometriosis is a
      risk factor for development of EESS and history and/or histological evidence for
      endometriosis is usually present. HRT is another acknowledged risk factor, mostly
      on the background of endometriosis. To our knowledge, this is the only report of
      EESS occurring in a woman on HRT treatment without background of endometriosis.
      CONCLUSION: EESS can occur without endometriosis and HRT may be an aetiological
      factor. The condition can mimic a chronic or acute abdominal pathology and
      laparoscopic core biopsy is the best way to achieve a diagnosis and formulate
      management.

PMID- 28494325
TI  - HIV-1 integrase inhibitor resistance among treatment naive patients in the West
      of Scotland.
AB  - BACKGROUND: Transmitted integrase inhibitor resistance is rare, with only a small
      number of cases reported world-wide to date. OBJECTIVES: The aim of this study
      was to assess whether transmitted integrase inhibitor resistance has occurred in
      Scotland and if so, could there be a case for performing genotypic integrase
      resistance testing at baseline. STUDY DESIGN: The study population consisted of
      106 treatment naive, newly diagnosed, HIV positive patients. The patient samples
      were collected between October 2015 and March 2016 at the time of HIV diagnosis
      and prior to initiation of anti-retroviral therapy. The integrase region was
      amplified and sequenced. RESULTS: We detected integrase inhibitor resistance
      (T66I/T) at baseline in one patient sample. This is a non-polymorphic mutation
      seen in patients receiving elvitegravir which confers high-level resistance to
      elvitegravir and intermediate resistance to raltegravir. A further 10 patients
      had accessory mutations which have minimal or no effect on susceptibility to
      integrase inhibitors. CONCLUSIONS: Transmitted integrase inhibitor resistance
      remains rare. The results of the present study do not support performing
      integrase resistance testing at baseline.

PMID- 28494326
TI  - MAIT cells and MR1-antigen recognition.
AB  - Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that
      recognise antigens presented by the monomorphic MHC-I related molecule, MR1.
      Distinct from the conventional MHC-restricted T cell system, MR1 presents small
      molecule precursors, derived from microbial biosynthesis of riboflavin, to
      activate the innate MAIT cell effector potential. Recent data demonstrates how:
      vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT
      cell development; variation in the MAIT cell antigen receptor sequence impacts
      MR1-antigen recognition; and most notably, how MR1 can capture chemical
      identities distinct from riboflavin precursors, including drugs and drug-like
      molecules. With mounting evidence demonstrating their roles in immunity and
      pathology, understanding the MAIT-MR1-antigen axis may have profound implications
      for human diseases.

PMID- 28494327
TI  - Magnetic field-induced effects on NMR properties.
AB  - In principle, all the NMR observables, spin-spin coupling J, nuclear shielding
      sigma and quadrupole coupling q, are magnetic field-dependent. The field
      dependence may be classified into two categories: direct and indirect (apparent)
      dependence. The former arises from the magnetic field-induced deformation of the
      molecular electronic cloud, while the latter stems from a slightly anisotropic
      orientation distribution of molecules, due to the interaction between the
      anisotropy of the molecular susceptibility tensor and the external magnetic
      field. Here we use 1,3,5-D3-benzene as a model system to investigate the indirect
      effect on the one-bond 1H-13C and 2H-13C spin-spin couplings (J couplings) and
      the 2H quadrupole coupling. Experiments carried out at four magnetic fields (4.7,
      9.4, 14.1, and 18.8 T) show that the indirect effect is significant already at
      the magnetic fields commonly used in NMR spectrometers. A joint fit of the data
      extracted at the different field strengths provides experimental results for the
      susceptibility anisotropy, 2H quadrupole coupling constant and the related
      asymmetry parameter, as well as the one-bond CH and CD coupling constants
      extrapolated to vanishing field strength. The field-induced contributions are
      found to exceed the commonly assumed error margins of the latter. The data also
      indicate a primary isotope effect on the one-bond CH coupling constant. There is
      a tendency to further increase the magnetic field of NMR spectrometers, which
      leads to more pronounced indirect contributions and eventually significant direct
      effects as well.

PMID- 28494328
TI  - Robust stability analysis of quaternion-valued neural networks with time delays
      and parameter uncertainties.
AB  - This paper addresses the problem of robust stability for quaternion-valued neural
      networks (QVNNs) with leakage delay, discrete delay and parameter uncertainties.
      Based on Homeomorphic mapping theorem and Lyapunov theorem, via modulus
      inequality technique of quaternions, some sufficient conditions on the existence,
      uniqueness, and global robust stability of the equilibrium point are derived for
      the delayed QVNNs with parameter uncertainties. Furthermore, as direct
      applications of these results, several sufficient conditions are obtained for
      checking the global robust stability of QVNNs without leakage delay as well as
      complex-valued neural networks (CVNNs) with both leakage and discrete delays.
      Finally, two numerical examples are provided to substantiate the effectiveness of
      the proposed results.

PMID- 28494329
TI  - Hopfield networks as a model of prototype-based category learning: A method to
      distinguish trained, spurious, and prototypical attractors.
AB  - We present an investigation of the potential use of Hopfield networks to learn
      neurally plausible, distributed representations of category prototypes. Hopfield
      networks are dynamical models of autoassociative memory which learn to recreate a
      set of input states from any given starting state. These networks, however, will
      almost always learn states which were not presented during training, so called
      spurious states. Historically, spurious states have been an undesirable side
      effect of training a Hopfield network and there has been much research into
      detecting and discarding these unwanted states. However, we suggest that some of
      these states may represent useful information, namely states which represent
      prototypes of the categories instantiated in the network's training data. It
      would be desirable for a memory system trained on multiple instance tokens of a
      category to extract a representation of the category prototype. We present an
      investigation showing that Hopfield networks are in fact capable of learning
      category prototypes as strong, stable, attractors without being explicitly
      trained on them. We also expand on previous research into the detection of
      spurious states in order to show that it is possible to distinguish between
      trained, spurious, and prototypical attractors.

PMID- 28494330
TI  - New models to support the professional education of health visitors: A
      qualitative study of the role of space and place in creating 'community of
      learning hubs'.
AB  - BACKGROUND: In response to a policy-driven workforce expansion in England new
      models of preparing health visitors for practice have been implemented.
      'Community of Learning hubs' (COLHs) are one such model, involving different
      possible approaches to student support in clinical practice placements (for
      example, 'long arm mentoring' or 'action learning set' sessions). Such models
      present opportunities for studying the possible effects of spatiality on the
      learning experiences of students and newly qualified health visitors, and on team
      relationships more broadly. OBJECTIVES: To explore a 'community of learning hub'
      model in health visitor education and reflect on the role of space and place in
      the learning experience and professional identity development of student health
      visitors. DESIGN: Qualitative research conducted during first year of
      implementation. SETTINGS: Three 'community of learning hub' projects based in two
      NHS community Trusts in London during the period 2013-2015. PARTICIPANTS:
      Managers and leads (n=7), practice teachers and mentors (n=6) and newly qualified
      and student health visitors (n=16). METHODS: Semi-structured, audio-recorded
      interviews analysed thematically. RESULTS: Participants had differing views as to
      what constituted a 'hub' in their projects. Two themes emerged around the spaces
      that shape the learning experience of student and newly qualified health
      visitors. Firstly, a generalised need for a 'quiet place' which allows pause for
      reflection but also for sharing experiences and relieving common anxieties.
      Secondly, the role of physical arrangements in open-plan spaces to promote access
      to support from more experienced practitioners. CONCLUSIONS: Attention to
      spatiality can shed light on important aspects of teaching and learning
      practices, and on the professional identities these practices shape and support.
      New configurations of time and space as part of educational initiatives can
      surface new insights into existing practices and learning models.

PMID- 28494331
TI  - Graduate nurses' evaluation of mentorship: Development of a new tool.
AB  - AIM: Develop and test an instrument to measure graduate-nurses' perceptions of a
      structured mentorship program. BACKGROUND: New graduate nurses may experience
      difficulties in the transition from student to practitioner. Mentoring is
      commonly used to support graduates. However, there is a lack of published tools
      measuring graduate nurses' perceptions of mentorship. As mentoring is resource
      intensive, development and testing of a validated tool are important to assist in
      determining program effectiveness. METHODS: A pretest-posttest interventional
      design was used. Following a critical review of literature and content experts'
      input, the 10-item National University Hospital Mentorship Evaluation (NUH ME)
      instrument was tested with a convenience sample of 83 graduate nurses.
      Psychometric tests included internal reliability, stability, content validity,
      and factor analysis. Changed scores were evaluated using paired samples t-test.
      RESULTS: Seventy-three graduates (88%) out of a possible 83 completed the pre-and
      post-program survey. Internal reliability was excellent with a Cronbach's alpha
      of 0.92. Test-retest reliability was stable over time (ICC=0.81). Exploratory
      factor analysis supported a 1-factor solution explaining 58.2% of variance.
      Paired samples t-test showed statistical significance between the pre- and post
      program scores (p<0.001). CONCLUSIONS: The NUH-ME measure was found to be valid
      and reliable. Confirmatory Factor Analysis of the tool with different groups of
      nursing graduates is required. Mentorship programs can be an effective
      recruitment and retention strategy, but are also resource intensive. Measuring
      new graduates' perceptions of mentoring contributes to program relevance in
      addressing their personal, professional and clinical skill development needs. As
      mentoring engages a diverse range of mentors, feedback through measurement may
      also positively alter organizational learning culture.

PMID- 28494332
TI  - Polymorphism in ABC transporter genes of Dirofilaria immitis.
AB  - Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and
      occasionally in humans. Prevention of the disease has been mainly by monthly use
      of the macrocyclic lactone (ML) endectocides during the mosquito transmission
      season. Recently, ML resistance has been confirmed in D. immitis and therefore,
      there is a need to find new classes of anthelmintics. One of the mechanisms
      associated with ML resistance in nematodes has been the possible role of ATP
      binding cassette (ABC) transporters in reducing drug concentrations at receptor
      sites. ABC transporters, mainly from sub-families B, C and G, may contribute to
      multidrug resistance (MDR) by active efflux of drugs out of the cell. Gene
      products of ABC transporters may thus serve as the targets for agents that may
      modulate susceptibility to drugs, by inhibiting drug transport. ABC transporters
      are believed to be involved in a variety of physiological functions critical to
      the parasite, such as sterol transport, and therefore may also serve as the
      target for drugs that can act as anthelmintics on their own. Knowledge of
      polymorphism in these ABC transporter genes in nematode parasites could provide
      useful information for the process of drug design. We have identified 15 ABC
      transporter genes from sub-families A, B, C and G, in D. immitis, by comparative
      genomic approaches and analyzed them for polymorphism. Whole genome sequencing
      data from four ML susceptible (SUS) and four loss of efficacy (LOE) pooled
      populations were used for single nucleotide polymorphism (SNP) genotyping. Out of
      231 SNPs identified in those 15 ABC transporter genes, 89 and 75 of them were
      specific to the SUS or LOE populations, respectively. A few of the SNPs
      identified may affect gene expression, protein function, substrate specificity or
      resistance development and may be useful for transporter inhibitor/anthelmintic
      drug design, or in order to anticipate resistance development.

PMID- 28494333
TI  - Implementing monitoring technologies in care homes for people with dementia: A
      qualitative exploration using Normalization Process Theory.
AB  - BACKGROUND: Ageing societies and a rising prevalence of dementia are associated
      with increasing demand for care home places. Monitoring technologies (e.g. bed
      monitoring systems; wearable location-tracking devices) are appealing to care
      homes as they may enhance safety, increase resident freedom, and reduce staff
      burden. However, there are ethical concerns about the use of such technologies,
      and it is unclear how they might be implemented to deliver their full range of
      potential benefits. OBJECTIVE: This study explored facilitators and barriers to
      the implementation of monitoring technologies in care homes. DESIGN: Embedded
      multiple-case study with qualitative methods. SETTING: Three dementia-specialist
      care homes in North-West England. PARTICIPANTS: Purposive sample of 24 staff
      (including registered nurses, clinical specialists, senior managers and care
      workers), 9 relatives and 9 residents. METHODS: 36 semi-structured interviews
      with staff, relatives and residents; 175h of observation; resident care record
      review. Data collection informed by Normalization Process Theory, which seeks to
      account for how novel interventions become routine practice. Data analysed using
      Framework Analysis. RESULTS: Findings are presented under three main themes: 1.
      Reasons for using technologies: The primary reason for using monitoring
      technologies was to enhance safety. This often seemed to override consideration
      of other potential benefits (e.g. increased resident freedom) or ethical concerns
      (e.g. resident privacy); 2. Ways in which technologies were implemented: Some
      staff, relatives and residents were not involved in discussions and decision
      making, which seemed to limit understandings of the potential benefits and
      challenges from the technologies. Involvement of residents appeared particularly
      challenging. Staff highlighted the importance of training, but staff training
      appeared mainly informal which did not seem sufficient to ensure that staff fully
      understood the technologies; 3. Use of technologies in practice: Technologies
      generated frequent alarms that placed a burden upon staff, but staff were able to
      use their contextual knowledge to help to counter some of this burden. Some
      technologies offered a range of data-gathering capabilities, but were not always
      perceived as useful complements to practice. CONCLUSION: Implementation of
      monitoring technologies may be facilitated by the extent to which the
      technologies are perceived to enhance safety. Implementation may be further
      facilitated through greater involvement of all stakeholders in discussions and
      decision-making in order to deepen understandings about the range of potential
      benefits and challenges from the use of monitoring technologies. Staff training
      might need to move beyond functional instruction to include deeper exploration of
      anticipated benefits and the underlying rationale for using monitoring
      technologies.

PMID- 28494334
TI  - Coincidence of role expectations between staff and volunteer members of drug free
      community coalitions.
AB  - Community coalitions have proliferated as a means of addressing a range of
      complex community problems. Such coalitions often consist of a small paid staff
      and volunteer members. The present study examines one likely contributor to
      coalition effectiveness: the degree of agreement on role expectations between
      paid staff and volunteer members. Role confusion occurs when paid staff and
      volunteers differ in their expectations of who is responsible for accomplishing
      specific tasks. Staff and volunteer members from 69 randomly selected Drug Free
      Coalitions in the United States as well as 21 Drug Free Coalitions in Connecticut
      were asked to respond to an online survey asking about 37 specific coalition
      tasks critical for effective coalition functioning and the degree to which paid
      staff and/or voluntary members should be responsible for accomplishing each. Our
      final sample consisted of 476 individuals from 35 coalitions. Using coalitions as
      the unit of analysis, we found significant differences between paid staff and
      volunteer coalition members on nine tasks reflecting four domains: meeting
      leadership and participation, (2) planning and implementation leadership, (3)
      publicity/media relations, and (4) logistical functions. Implications of these
      differences and ways that evaluators could help coalitions deal with differing
      role expectations were discussed.

PMID- 28494335
TI  - Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction
      for the simultaneous determination of 12 new antidepressants and 2 antipsychotics
      in whole blood by gas chromatography-mass spectrometry.
AB  - Antidepressant drugs are widely used in the treatment of different psychiatric
      disorders, as well as in conjunction with antipsychotics for the treatment of
      major depressive disorder. In this study, a simple and rapid ultrasound-assisted
      low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME)
      method was developed for the simultaneous determination of 12 new antidepressants
      (norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide,
      melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram,
      paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood
      by gas chromatography-mass spectrometry (GC-MS). Different parameters affecting
      the UA-LDS-DLLME were optimized and the optimal conditions were as follows:
      100MUL of toluene as extraction solvent, extraction pH 12 and 3min of ultrasound
      stirring. Good linearity (R2>=0.991) was obtained at the concentration range of
      15-1500ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline
      and citalopram, and 5-500ng/mL for agomelatine, mirtazapine, moclobemide, N
      desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The
      intra-day and inter-day precision were all less than 10%, and accuracy of intra
      day and inter-day were in the range of -12.7% to 7.9% and -13.9 to 11.8%,
      respectively. The extraction recoveries of most analytes were more than 60%. The
      UA-LDS-DLLME/GC-MS method was demonstrated with acceptable precision, accuracy
      and good specificity for the simultaneous determination of 12 antidepressants and
      2 antipsychotics, and has been successfully applied in a real case.

PMID- 28494336
TI  - Metabolite profiling of flavonols and in vitro antioxidant activity of young
      shoots of wild Humulus lupulus L. (hop).
AB  - Humulus lupulus L., commonly named hop, is well-known for its sedative and
      estrogenic activity. While hop cones are widely characterized, only few works
      have been carried out on the young shoots of this plant. In the light of this,
      the aim of this study was to identify for the first time the flavonoids present
      in young hop shoots and to compare the composition of samples harvested from
      different locations in Northern Italy with their antioxidant activity. The
      samples were extracted by means of dynamic maceration with methanol. The HPLC
      UV/DAD, HPLC-ESI-MS and MS2 analysis were carried out by using an Ascentis C18
      column (250*4.6mm I.D., 5MUm), with a mobile phase composed of 0.1M formic acid
      in both water and acetonitrile, under gradient elution. Quercetin and kaempferol
      glycosides were the main compounds identified and quantified in hop shoot
      extracts. Total flavonols ranged from 2698+/-185 to 517+/-48MUg/g (fresh weight).
      The antioxidant activity was determined by means of the radical scavenging
      activity assay against diphenylpicrylhydrazyl (DPPH) and by using a
      photochemiluscence assay with a Photochem(r) apparatus. The results showed that
      hop shoots represent a new source of flavonols; therefore, they can be useful for
      a possible incorporation in the diet as a functional food or applied in the
      nutraceutical ambit.

PMID- 28494337
TI  - Quantification of apigenin trimethyl ether in rat plasma by liquid chromatography
      tandem mass spectrometry: Application to a pre-clinical pharmacokinetic study.
AB  - Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE) is a naturally occurring
      polymethoxyflavone with a wide range of health-promoting activities. In this
      study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method was developed and validated for the quantification of ATE in rat plasma.
      Protein precipitation was applied as plasma clean-up procedure; the electrospray
      ionization was operated in its positive ion mode while ATE and formononetin
      (internal standard) were measured by multiple reactions monitoring (ATE: m/z
      313.1->298.1; formononetin: 269.2->213.3). This LC-MS/MS method displayed good
      selectivity, sensitivity (lower limit of quantification=2.5ng/ml), accuracy (both
      intra- and inter-day analytical recovery within 100+/-10%) and precision (both
      intra- and inter-day RSD <10%). The matrix effect was found to be insignificant.
      The pharmacokinetic profiles of ATE were subsequently examined in Sprague-Dawley
      rats after single oral administration (10mg/kg). When given in an aqueous
      suspension, ATE was slowly absorbed with quite low plasma exposure (AUC). Fasting
      further attenuated its oral absorption and led to ~70% drops in average maximal
      plasma concentration (Cmax) and AUC. When dosed in a solution formulated with 2
      hydroxypropyl-beta-cyclodextrin, the oral absorption of ATE was substantially
      improved with ~500% increases in average Cmax and AUC. Clearly, aqueous
      solubility has been identified as a barrier to the oral absorption of ATE. The
      information obtained from this study will facilitate further medicinal
      exploration on ATE.

PMID- 28494338
TI  - Simultaneous analysis of regorafenib and sorafenib and three of their metabolites
      in human plasma using LC-MS/MS.
AB  - A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, performed
      by electrospray ionization in positive mode using a triple quadrupole mass
      spectrometry, has been developed and validated for the simultaneous determination
      of regorafenib (REGO), its two metabolites regorafenib-M2 and regorafenib-M5,
      sorafenib (SORA), and its N-oxide metabolite in human plasma. Separation is
      achieved on an Hypersil Gold(r) column using a gradient elution of 10mM ammonium
      formate containing 0.1% formic acid (A) and acetonitrile containing 0.1% formic
      acid (B) at a flow rate of 0.3mL/min. After addition of two internal standards
      and a protein precipitation, the supernatant is diluted two-fold in a 0.1% (v/v)
      formic acid solution. Two selected reaction monitoring transitions are used, for
      each analyte, one for quantitation and the second one for confirmation. The
      standard curves are ranged from 50 to 5 000ng/mL for REGO and its metabolites and
      80 to 5 000ng/mL for SORA and its metabolite and were fitted to a 1/x weighted
      linear regression model. The method also showed satisfactory results in terms of
      sensitivity, specificity, precision (intra- and inter-day CV from 2.4 to 10.2%),
      accuracy (from 91.0 to 111.7%), recovery as well as stability of the analytes
      under various conditions. The method is usually used in clinical practice in
      order to improve the SORA treatment for renal carcinoma, REGO treatment for
      colorectal cancer and both for hepatocellular carcinoma.

PMID- 28494339
TI  - Application of protein A-modified capillary-channeled polymer polypropylene
      fibers to the quantitation of IgG in complex matrices.
AB  - Polypropylene (PP) capillary-channeled polymer (C-CP) fibers loaded with
      recombinant Staphyloccocus aureus protein A (rSPA) were used as an affinity
      chromatography stationary phase for the quantitation of immunoglobulin G (IgG) in
      complex biological matrices. Optimization of the chromatographic method regarding
      mobile phase components and load/elution conditions was performed. The six-minute
      analysis, including a load step with 12mM phosphate at pH 7.4, an elution step
      with 0.025% phosphoric acid and a re-equilibration step, was employed for
      quantitation of IgG1 from 0.075 to 3.00mgmL-1 in an IgG-free CHO cell supernatant
      matrix. Quantification of IgG1 content in a different CHO cell line was
      accomplished using the external calibration curve as well as using a standard
      addition approach. The high level of agreement between the two approaches
      suggests that the protein A-modified C-CP fiber phase is immune from matrix
      effects due to concomitant species such as host cell proteins (HCPs), host cell
      DNA, media components and other leachables and extractables. The inter-day and
      intra-day precision of the method were 3.1 and 3.5%RSD respectively for a single
      column. Column-to-column variability was 1.31 and 6.62%RSD for elution time and
      peak area, respectively, across columns prepared in different batches. The method
      reported here is well-suited for IgG analysis in complex harvest cell culture
      media in both the development and production environments.

PMID- 28494340
TI  - Simple and rapid quantification of vancomycin in serum, urine and
      peritoneal/pleural effusion via UHPLC-MS/MS applicable to personalized antibiotic
      dosing research.
AB  - Management of the therapy of life-threatening bacterial infection is extremely
      based on an optimal antibiotic treatment. Achieving the correct vancomycin dosage
      in blood and target tissues can be complicated in special situations, e.g., where
      large fluid sequestration and/or acute renal failure occur. A UHPLC-MS/MS method
      operating in electrospray (ESI) positive ion mode was applied for the
      determination of vancomycin in serum, urine and peritoneal/pleural effusion.
      Sample pretreatment was composed of dilution and simple protein precipitation
      where only a small volume (50MUL) of serum, urine or peritoneal/pleural effusion
      was required. The separation of vancomycin was performed on a Meteoric Core C18
      BIO column (100*4.6mm, 2.7MUm) by gradient elution with 0.1% formic acid in water
      and acetonitrile. The total time of analysis was 4.5min. The method was found to
      be linear in the range of 2-60MUM (or 0.5-10MUM) for serum, 0.27-10MUM (or 2
      60MUM) for peritoneal/pleural effusion and 25-300MUM for urine, which was
      adequate for the determination of vancomycin in patient samples. The intra- and
      inter-day precision was below 8% RSD, and accuracy was from 89 to 104%. The
      UHPLC/MS-MS method offers a fast and reliable approach to determine vancomycin
      concentrations in three different human body fluid samples (serum, urine and
      peritoneal/pleural effusion) with a simple sample pretreatment that was the same
      for all selected specimens. This method should be applicable to large sample
      series in clinical (pharmacokinetic/pharmacodynamic) studies.

PMID- 28494341
TI  - Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but
      not gelatinase activities.
AB  - Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging
      and antiinflammatory activities; however, little is known about the effects of
      persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer
      (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and
      antiproliferative effects of a persimmon phenolic extract (80% acetone in water),
      using an in vivo model of experimental colitis and a model of cancer cell
      invasion. Our results show, for the first time, a beneficial effect of a
      persimmon phenolic extract in the attenuation of experimental colitis and a
      potential antiproliferative effect on cultured colon cancer cells. Administration
      of persimmon phenolic extract to mice with TNBS-induced colitis led to a
      reduction in several functional and histological markers of colon inflammation,
      namely: attenuation of colon length decrease, reduction of the extent of visible
      injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate,
      reduction of mucosal hemorrhage and reduction of general histological features of
      colon inflammation. In vitro studies also showed that persimmon phenolic extract
      successfully impaired cell proliferation and invasion in HT-29 cells. Further
      investigation showed a decreased expression of COX-2 and iNOS in the colonic
      tissue of colitis mice, two important mediators of intestinal inflammation, but
      there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the
      role of inflammatory processes in the progression of CRC and the important link
      between inflammation and cancer, our results highlight the potential of persimmon
      polyphenols as a pharmacological tool in the treatment of patients with IBD.

PMID- 28494342
TI  - Genome sequence variation among isolates of monkey B virus (Macacine
      alphaherpesvirus 1) from captive macaques.
AB  - Complete genome sequences of 19 strains of monkey B virus (Macacine
      alphaherpesvirus 1; BV) isolated from several macaque species were determined. A
      low level of sequence variation was present among BV isolates from rhesus
      macaques. Most variation among BV strains isolated from rhesus macaques was
      located in regions of repetitive or quasi-repetitive sequence. Variation in
      coding sequences (polypeptides and miRNAs) was minor compared to regions of non
      coding sequences. Non-coding sequences in the long and short repeat regions of
      the genome did however exhibit islands of conserved sequence. Oral and genital
      isolates from a single monkey were identical in sequence and varied only in the
      number of iterations of repeat units in several areas of repeats. Sequence
      variation between BV isolates from different macaque species (different BV
      genotypes) was much greater and was spread across the entire genome, confirming
      the existence of different genotypes of BV in different macaque species.

PMID- 28494343
TI  - Gene end-like sequences within the 3' non-coding region of the Nipah virus genome
      attenuate viral gene transcription.
AB  - The regulation of transcription during Nipah virus (NiV) replication is poorly
      understood. Using a bicistronic minigenome system, we investigated the
      involvement of non-coding regions (NCRs) in the transcriptional re-initiation
      efficiency of NiV RNA polymerase. Reporter assays revealed that attenuation of
      NiV gene expression was not constant at each gene junction, and that the
      attenuating property was controlled by the 3' NCR. However, this regulation was
      independent of the gene-end, gene-start and intergenic regions. Northern blot
      analysis indicated that regulation of viral gene expression by the phosphoprotein
      (P) and large protein (L) 3' NCRs occurred at the transcription level. We
      identified uridine-rich tracts within the L 3' NCR that are similar to gene-end
      signals. These gene-end-like sequences were recognized as weak transcription
      termination signals by the viral RNA polymerase, thereby reducing downstream gene
      transcription. Thus, we suggest that NiV has a unique mechanism of
      transcriptional regulation.

PMID- 28494344
TI  - PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus
      by suppressing early immune responses in swine.
AB  - Previous studies have identified a functional role of PA-X for influenza viruses
      in mice and avian species; however, its role in swine remains unknown. Toward
      this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple
      reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X
      in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral
      replication and host protein synthesis shutoff, and inhibited the mRNA levels of
      type I IFNs and proinflammatory cytokines in porcine cells. A delay of
      proinflammatory responses was observed in lungs of pigs infected by wild type SIV
      (Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted
      more efficiently than Sw-FS in pigs. These results highlight the importance of PA
      X in the moderation of virulence and immune responses of TR SIV in swine, which
      indicated that PA-X is a pro-virulence factor in TR SIV in pigs.

PMID- 28494345
TI  - Weight gain after STN-DBS: The role of reward sensitivity and impulsivity.
AB  - Weight gain has been reported after deep brain stimulation of the subthalamic
      nucleus (STN-DBS), a widely used treatment for Parkinson's disease (PD). This
      nucleus has been repeatedly found to be linked both to reward and to inhibitory
      control, two key aspects in the control of food intake. In this study, we
      assessed whether weight gain experienced by patients with PD after STN-DBS, might
      be due to an alteration of reward and inhibitory functions. Eighteen patients
      with PD were compared to eighteen healthy controls and tested three times: before
      surgery, in ON medication and after surgery, respectively five days after the
      implantation in ON medication/OFF stimulation and at least three months after
      surgery in ON medication/ON stimulation. All participants were assessed for
      depression (Beck Depression Inventory), anhedonia (Snaith-Hamilton Pleasure
      Scale) and impulsiveness (Barratt Impulsiveness Scale). They performed a battery
      of tests assessing food reward sensitivity (Liking, Wanting and Preference) and a
      food go/no-go task. Results showed that body weight significantly increased after
      STN-DBS. A few days after surgery, patients were slower and more impulsive in the
      go/no-go task, showed a higher preference for high calorie (HC) foods and rated
      foods as less tasty. Months after subthalamic stimulation, the performance on the
      go/no-go task improved while no differences were observed in reward sensitivity.
      Interestingly, weight gain resulted greater in patients with higher levels of
      attentional impulsiveness pre-surgery, higher wanting for low calorie (LC) foods
      and impulsivity in the go/no-go task in ON medication/ON stimulation. However,
      only wanting and attentional impulsivity significantly predicted weight change.
      Furthermore, weight gain resulted associated with the reduction of l-Dopa after
      surgery and disease's duration. In conclusion, our findings are consistent with
      the view that weight gain in PD after STN-DBS has a multifactorial nature, which
      reflects the complex functional organization of the STN.

PMID- 28494346
TI  - Glutamatergic and neural dysfunction in postpartum depression using magnetic
      resonance spectroscopy.
AB  - Although postpartum depression (PPD) is a prevalent subtype of major depressive
      disorder, neuroimaging studies on PPD are rare, particularly those identifying
      neurochemical abnormalities obtained by proton magnetic resonance spectroscopy
      (1H-MRS). The dorsolateral prefrontal (DLPF) and the anterior cingulate gyrus
      (ACG) are part of the neural pathways involved in executive functions and
      emotional processing, and both structures have been implicated in the
      neurobiology of depressive disorders. This study aimed to evaluate brain
      metabolites abnormalities in women with PPD compared with healthy postpartum (HP)
      women. Thirty-six PPD (34 without antidepressants) and 25 HP women underwent a 1H
      MRS acquired on a 3-T MRI system, with the volume of interest positioned in ACG
      and DLPF. An ANCOVA was conducted with age, postpartum time, and contraceptive
      type as covariates. PPD group presented significantly lower Glutamate+Glutamine
      (Glx, -0.95mM) and N-acetylaspartate+N-acetylaspartylglutamate (NAA, -0.60mM)
      values in DLPF. There were no significant differences between groups in ACG, but
      we found a significant increase of Glutamate (Glu, 2.18mM) and Glx (1.84mM) in
      participants using progestogen-only contraceptives. These findings suggest
      glutamatergic dysfunction and neuronal damage in the DLPF of PPD patients,
      similarly to other subtypes of depressive disorders. Progestogens seem to
      interfere in the neurochemistry of ACG.

PMID- 28494347
TI  - Structural brain abnormalities in patients with type I bipolar disorder and
      suicidal behavior.
AB  - Some studies have identified brain morphological changes in the frontolimbic
      network (FLN) in bipolar subjects who attempt suicide (SA). The present study
      investigated neuroanatomical abnormalities in the FLN to find a possible neural
      signature for suicidal behavior in patients with bipolar disorder type I (BD-I).
      We used voxel-based morphometry to compare euthymic patients with BD-I who had
      attempted suicide (n=20), who had not attempted suicide (n=19) and healthy
      controls (HCs) (n=20). We also assessed the highest medical lethality of their
      previous SA. Compared to the participants who had not attempted suicide, the
      patients with BD-I who had attempted suicide exhibited significantly increased
      gray matter volume (GMV) in the right rostral anterior cingulate cortex (ACC),
      which was more pronounced and extended further to the left ACC in the high
      lethality subgroup (p<0.05, with family-wise error (FWE) correction for multiple
      comparisons using small-volume correction). GMV in the insula and orbitofrontal
      cortex was also related to suicide lethality (p<0.05, FWE-corrected). The current
      findings suggest that morphological changes in the FLN could be a signature of
      previous etiopathogenic processes affecting regions related to suicidality and
      its severity in BD-I patients.

PMID- 28494348
TI  - Withaferin A Inhibits Prostate Carcinogenesis in a PTEN-deficient Mouse Model of
      Prostate Cancer.
AB  - We recently demonstrated that AKT activation plays a role in prostate cancer
      progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT
      inhibition and Par-4 induction suppressed prostate cancer progression in
      preclinical models. Here, we investigate the chemopreventive effect of the
      phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten
      conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment
      was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle
      over 45 weeks. Oral administration of WA for 45 weeks effectively inhibited
      primary tumor growth in comparison to vehicle controls. Pathological analysis
      showed the complete absence of metastatic lesions in organs from WA-treated mice,
      whereas discrete metastasis to the lungs was observed in control tumors.
      Immunohistochemical analysis revealed the down-regulation of pAKT expression and
      epithelial-to-mesenchymal transition markers, such as beta-catenin and N
      cadherin, in WA-treated tumors in comparison to controls. This result
      corroborates our previous findings from both cell culture and xenograft models of
      prostate cancer. Our findings demonstrate that the daily administration of a
      phytonutrient that targets AKT activation provides a safe and effective treatment
      for prostate cancer in a mouse model with strong potential for translation to
      human disease.

PMID- 28494349
TI  - Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell
      of-Origin Sarcoma Models.
AB  - Trabectedin has been approved for second-line treatment of soft tissue sarcomas.
      However, its efficacy to target sarcoma initiating cells has not been addressed
      yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and
      undifferentiated pleomorphic sarcoma (UPS) developed from transformed human
      mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in
      the cell type responsible for initiating sarcomagenesis and their derived cancer
      stem cells (CSC) subpopulations. We found that low nanomolar concentrations of
      trabectedin efficiently inhibited the growth of sarcoma-initiating cells, induced
      cell cycle arrest, DNA damage and apoptosis. Interestingly, trabectedin treatment
      repressed the expression of multiple genes responsible for the development of the
      CSC phenotype, including pluripotency factors, CSC markers and related signaling
      pathways. Accordingly, trabectedin induced apoptosis and reduced the survival of
      CSC-enriched tumorsphere cultures with the same efficiency that inhibits the
      growth of bulk tumor population. In vivo, trabectedin significantly reduced the
      mitotic index of MRCLS xenografts and inhibited tumor growth at a similar extent
      to that observed in doxorubicin-treated tumors. Combination of trabectedin with
      campthotecin (CPT), a chemotherapeutic drug that shows a robust anti-tumor
      activity when combined with alkylating agents, resulted in a very strong
      synergistic inhibition of tumor cell growth and highly increased DNA damage and
      apoptosis induction. Importantly, the enhanced anti-tumor activity of this
      combination was also observed in CSC subpopulations. These data suggest that
      trabectedin and CPT combination may constitute a novel strategy to effectively
      target both the cell-of-origin and CSC subpopulations in sarcoma.

PMID- 28494350
TI  - Liquid chromatography-tandem mass spectrometry quantification of acetamiprid and
      thiacloprid residues in butterbur grown under regulated conditions.
AB  - An analytical method was developed to quantify the residual levels of the
      neonicotinoid insecticides, acetamiprid and thiacloprid, in field-incurred
      butterbur samples using liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Samples were extracted with acetonitrile and partitioned with
      dichloromethane. After partitioning, purification was conducted using a
      Florisil(r) cartridge. Linearity of a matrix-matched calibration curve of the two
      compounds over a concentration range of 0.004-0.4MUg/g was excellent, with
      determination coefficients (R2)>=0.9998. The limits of detection (LOD) and
      quantitation (LOQ) for both acetamiprid and thiacloprid were 0.0006 and
      0.002mg/kg, respectively. The average recoveries for acetamiprid and thiacloprid
      at two spiking levels (0.02 and 0.1mg/kg, i.e., 10*LOQ and 50*LOQ) were between
      78.23 to 82.17%, with relative standard deviations (RSDs)<=7.22%. The method was
      successfully applied to field-incurred samples treated with a commercial
      pesticide product, either once (zero or 7 days before harvest) or twice (0 and 7,
      7 and 14, or 14 and 21 days before harvest). The highest and lowest residues were
      obtained for the 7 and 0 days' treatment and the 21 and 14 days' treatment,
      respectively. The developed method is simple and accurate and can be extrapolated
      to other leafy vegetables.

PMID- 28494351
TI  - Development and validation of a sensitive UPLC-MS/MS instrumentation and alkaline
      nitrobenzene oxidation method for the determination of lignin monomers in wheat
      straw.
AB  - A method to determine the lignin monomers (p-hydroxybenzaldehyde, vanillin and
      syringaldehyde) in plant cell wall of wheat internode was developed and validated
      using a high-throughput nitrobenzene oxidation step and ultra performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) for quantification. UPLC
      analyses were carried out using an reversed phase C18 column (ACQUITY UPLC BEH,
      1.7MUm, 2.1*100mm) and gradient elution with water and acetonitrile. This method
      was completely validated in terms of analyzing speed, linearity, sensitivity,
      limits of detection (LODs) and limits of quantification (LOQs).The three lignin
      monomers were successfully separated within 6min and only 2min were required to
      regain its equilibrium. The method linearity with regression coefficients values
      (R2) greater than 0.997. Additionally, LODs ranged from 0.21 to 0.89MUgL-1 and
      LOQs ranged from 0.69 to 2.95MUgL-1. The applicability of this analytical
      approach for determining the three lignin monomers was confirmed by the
      successful analysis of real samples of wheat stem internodes. The nitrobenzene
      oxidation method was used for the analysis of lignin monomers. We have optimized
      the treatment temperature (170 degrees C, 1h) and realized the high-throughput
      using the microwave digestion instrument. Recovery of this extraction method
      ranged from 68.4% to 77.7%. The analysis result showed that the guaiacyl unit (G)
      was the major component of lignin and there was a higher content of the syringyl
      unit (S) than that of the hydroxybenzyl unit (H).

PMID- 28494352
TI  - IL-33 protects murine viral fulminant hepatitis by targeting coagulation hallmark
      protein FGL2/fibroleukin expression.
AB  - Fulminant hepatitis (FH) is characterized by rapid liver failure and high
      mortality. The pathogenesis of viral FH includes virus-induced immune activation,
      inflammation, and subsequent hepatic apoptosis and necrosis. However, the
      mechanisms that underlie FH progression are unclear. IL-33 is a member of the IL
      1-related cytokines, considered to be an "alarmin" that participates in various
      diseases, but its precise role in the coagulation of FH is not very clear. In our
      study, we found that IL-33 is significantly elevated in mice infected with murine
      hepatitis virus strain 3 (MHV-3). This is accompanied by an increase in pro
      coagulant fibrinogen-like protein 2 (FGL2) in the liver. Previous studies have
      suggested that an increase in FGL2 is diagnostic of FH and liver necrosis, and
      animals with no FGL2 had better survivorship during FH. Our studies showed that
      IL-33 administration in a MHV-3 infection promoted survival during FH, with a
      significant reduction in FGL2 expression and liver inflammation. In vitro IL-33
      treatment abrogated MHV-3 and IFN-gamma induced FGL2 expression in RAW264.7 and
      THP-1 cells, respectively. In conclusion, our research suggests that IL-33
      protects against viral fulminant hepatitis in mice by antagonizing expression of
      the pro-coagulant protein FGL2.

PMID- 28494353
TI  - Removal of pesticides and ecotoxicological changes during the simultaneous
      treatment of triazines and chlorpyrifos in biomixtures.
AB  - Biopurification systems constitute a biological approach for the treatment of
      pesticide-containing wastewaters produced in agricultural activities, and contain
      an active core called biomixture. This work evaluated the performance of a
      biomixture to remove and detoxify a combination of three triazine herbicides
      (atrazine/terbuthylazine/terbutryn) and one insecticide (chlorpyrifos), and this
      efficiency was compared with dissipation in soil alone. The potential enhancement
      of the process was also assayed by bioaugmentation with the ligninolytic fungi
      Trametes versicolor. Globally, the non-bioaugmented biomixture exhibited faster
      pesticide removal than soil, but only in the first stages of the treatment. After
      20 d, the largest pesticide removal was achieved in the biomixture, while
      significant removal was detected only for chlorpyrifos in soil. However, after 60
      d the removal values in soil matched those achieved in the biomixture for all the
      pesticides. The bioaugmentation failed to enhance, and even significantly
      decreased the biomixture removal capacity. Final removal values were 82.8% (non
      bioaugmented biomixture), 43.8% (fungal bioaugmented biomixture), and 84.7%
      (soil). The ecotoxicological analysis revealed rapid detoxification (from 100 to
      170 TU to <1 TU in 20 d) towards Daphnia magna in the biomixture and soil, and
      slower in the bioaugmented biomixture, coinciding with pesticide removal. On the
      contrary, despite important herbicide elimination, no clear detoxification
      patterns were observed in the phytotoxicity towards Lactuca sativa. Findings
      suggest that the proposed biomixture is useful for fast removal of the target
      pesticides; even though soil also removes the agrochemicals, longer periods would
      be required. On the other hand, the use of fungal bioaugmentation is discouraged
      in this matrix.

PMID- 28494354
TI  - Development of collection, storage and analysis procedures for the quantification
      of cyclic volatile methylsiloxanes in wastewater treatment plant effluent and
      influent.
AB  - A reliable and accurate method for collection and analysis of
      octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and
      dodecamethylcyclohexasiloxane (D6) in wastewater treatment plant influent,
      effluent and surface waters was developed. Due to the use of cyclic volatile
      methylsiloxanes (cVMS) in industrial and consumer products including some
      personal care products, the wastewater stream represents a potential post-use
      disposal route and cVMS may subsequently enter the environment through wastewater
      treatment plant effluents. cVMS in the environment has come under increased
      regulatory scrutiny with regard to their potential for persistence,
      bioaccumulation and toxicity indicating a need for monitoring programs with
      reliable analytical methods. The developed method is unique in that it utilizes
      low density polyethylene (LDPE) to inhibit loss of cVMS during sampling and
      transport to the laboratory. The samples are then processed with a simple solvent
      extraction and analyzed by gas chromatography mass spectrometry with stable
      isotope internal standard calibration. This method utilizes readily available
      laboratory supplies and requires minimal field processing, reducing contamination
      potential. Method detection limits of 17 ng/L, 57 ng/L, and 20 ng/L were obtained
      for D4, D5, and D6, respectively. Additionally a robust quality control program
      was employed to ensure sample integrity. The method described herein can readily
      be adopted for use in monitoring studies where the amount of cVMS in water
      samples will be quantified.

PMID- 28494355
TI  - A hierarchical assembly of flower-like hybrid Turkish black radish peroxidase
      Cu2+ nanobiocatalyst and its effective use in dye decolorization.
AB  - Effective dye decolorization in wastewater still shows a big challenge. Although
      the biological methods, especially using enzymes, offer alternative and effective
      process for dye degradation and overcome the limitations of chemical and physical
      methods such as the instability, lack of reusability and high cost of free
      enzymes strictly, which limit their use in many scientific and technical
      applications. Enzymes rapidly lose their activities in aqueous solutions and
      against environmental changes due to their very susceptibility and unfavorable
      conformations. Herein, we report preparation of the enzyme-inorganic hybrid
      nanostructures with flower-like shape consisting of Turkish black radish
      peroxidase and Cu2+ metal ions using an encouraging enzyme immobilization
      approach. The peroxidase-Cu2+ hybrid nanoflowers (NFs) exhibited enhanced
      stability and activity towards various pH values and provided excellent dye
      decolorization efficiency for Victoria blue (VB) dye with more than 90% within 1
      h. The NFs were also repeatedly used in efficient and caused 77% VB
      decolorization efficiency even at tenth cycles. However, to the best of our
      knowledge, for the first time, we prepared peroxidase enzyme isolated from
      Turkish black radish incorporated NFs and used them for dye decolorization. We
      believe that the NFs can be promising materials for dye decolorization in real
      wastewater treatment.

PMID- 28494356
TI  - Appraising the role of environment friendly chelants in alleviating lead by
      Coronopus didymus from Pb-contaminated soils.
AB  - In a screenhouse experiment, we investigated the role of two environment friendly
      chelants, Ammonium molybdate and EDDS for Pb mobilisation and its extraction by
      Coronopus didymus under completely randomized controlled conditions. Seedlings of
      C. didymus were grown in pots having Pb-contaminated soil (1200 and 2200 mg kg-1)
      for 6 weeks. Plants were harvested, 1 week after the addition of A. molybdate and
      EDDS. Results revealed that A. molybdate and EDDS enhanced the uptake and
      accumulation of Pb in roots and shoots of C. didymus. At 2200 mg kg-1 Pb level,
      compared to Pb-alone treatment, the maximal concentration of Pb was increased
      upto ~10% and ~19%, in roots whereas ~8% and ~18%, respectively, in shoots on
      addition of 2 mmol kg-1 A. molybdate and EDDS. Additionally, Pb + EDDS treatments
      enhanced the plant biomass and triggered strong antioxidative response, more
      efficaciously than Pb + A. molybdate and Pb-alone treated plants. In this study,
      EDDS relative to A. molybdate was more efficient in mobilising and extracting Pb
      from soil. Although, EDDS followed by A. molybdate had good efficacy in
      mitigating Pb from contaminated soils but C. didymus itself has the inherent
      affinity to tolerate and accumulate Pb from contaminated soils and hence in
      future, can be used either alone or with some other eco-friendly amendments for
      soil remediation purposes.

PMID- 28494357
TI  - Biosurfactant-producing microorganism Pseudomonas sp. SB assists the
      phytoremediation of DDT-contaminated soil by two grass species.
AB  - Phytoremediation together with microorganisms may confer the advantages of both
      phytoremediation and microbial remediation of soils containing organic
      contaminants. In this system biosurfactants produced by Pseudomonas sp. SB may
      effectively help to increase the bioavailability of organic pollutants and
      thereby enhance their microbial degradation in soil. Plants may enhance the
      rhizosphere environment for microorganisms and thus promote the bioremediation of
      contaminants. In the present pot experiment study,
      dichlorodiphenyltrichloroethane (DDT) residues underwent an apparent decline
      after soil bioremediation compared with the original soil. The removal efficiency
      of fertilizer + tall fescue, fertilizer + tall fescue + Pseudomonas, fertilizer +
      perennial ryegrass, and fertilizer + perennial ryegrass + Pseudomonas treatments
      were 59.4, 65.6, 69.0, and 65.9%, respectively, and were generally higher than
      that in the fertilizer control (40.3%). Principal coordinates analysis (PCoA)
      verifies that plant species greatly affected the soil bacterial community
      irrespective of inoculation with Pseudomonas sp. SB. Furthermore, community
      composition analysis shows that Proteobacteria, Acidobacteria and Actinobacteria
      were the three dominant phyla in all groups. In particular, the relative
      abundance of Pseudomonas for fertilizer + tall fescue + Pseudomonas (0.25%) was
      significantly greater than fertilizer + tall fescue and this was related to the
      DDT removal efficiency.

PMID- 28494358
TI  - Herbicide effects on the growth and photosynthetic efficiency of Cassiopea
      maremetens.
AB  - Herbicides from agricultural run-off have been measured in coastal systems of the
      Great Barrier Reef over many years. Non-target herbicide exposure, especially
      photosystem II herbicides has the potential to affect seagrasses and other marine
      species. The symbiotic benthic jellyfish Cassiopea maremetens is present in
      tropical/sub-tropical estuarine and marine environments. Jellyfish (n = 8 per
      treatment) were exposed to four separate concentrations of agricultural
      formulations of diuron or hexazinone to determine their sensitivity and potential
      for recovery to pulsed herbicide exposure. Jellyfish growth, symbiont
      photosynthetic activity and zooxanthellae density were analysed for herbicide
      induced changes for 7 days followed by a 7 day recovery period. Both the
      jellyfish and endosymbiont were more sensitive to diuron than hexazinone. The 7
      day EC50 for jellyfish growth was 0.35 MUg L-1 for Diuron and 17.5 MUg L-1 for
      Hexazinone respectively. Diuron exposure caused a significant decrease (p < 0.05)
      in jellyfish growth at 0.1 MUg L-1, a level that is below the regional Great
      Barrier Reef guideline value. Jellyfish recovery was rapid with growth rates
      similar to control animals following removal from herbicide exposure. Both diuron
      and hexazinone caused significant decreases in photosynthetic efficiency
      (effective quantum yield) in all treatment concentrations (0.1 MUg L-1 and above)
      and this effect continued in the post-exposure period. As this species is
      frequently found in near-shore environments, they may be particularly vulnerable
      to herbicide run-off.

PMID- 28494359
TI  - Impacts of solids retention time on trace organic compound attenuation and
      bacterial resistance to trimethoprim and sulfamethoxazole.
AB  - Bacteria can grow in the presence of trimethoprim and sulfamethoxazole by
      expressing antibiotic resistance genes or by acquiring thymine or thymidine from
      environmental reservoirs to facilitate DNA synthesis. The purpose of this study
      was to evaluate whether activated sludge serves as a reservoir for thymine or
      thymidine, potentially impacting the quantification of antibiotic resistant
      bacteria. This study also assessed the impacts of varying solids retention time
      (SRT) on trimethoprim and sulfamethoxazole removal during wastewater treatment
      and single and multi-drug resistance. When assayed in the presence of the
      antibiotics at standard clinical concentrations, up to 40% increases in the
      relative prevalence of resistant bacteria were observed with (1) samples manually
      augmented with reagent-grade thymidine, (2) samples manually augmented with
      sonicated biomass (i.e., cell lysate), (3) samples manually augmented with
      activated sludge filtrate, and (4) activated sludge samples collected from
      reactors with longer SRTs. These observations suggest that longer SRTs may select
      for antibiotic resistant bacteria and/or result in false positives for antibiotic
      resistance due to higher concentrations of free thymine, thymidine, or other
      extracellular constituents.

PMID- 28494360
TI  - Fluoride induces apoptosis in H9c2 cardiomyocytes via the mitochondrial pathway.
AB  - Numerous studies have shown that chronic excessive fluoride intake can adversely
      affect different organ systems. In particular, the cardiovascular system is
      susceptible to disruption by a high concentration of fluoride. The objectives of
      this study were to explore the mechanism of apoptosis by detecting the toxic
      effects of different concentrations of sodium fluoride (NaF) in H9c2 cells
      exposed for up to 96 h. NaF not only inhibited H9c2 cell proliferation but also
      induced apoptosis and morphological damage. With increasing NaF concentrations,
      early apoptosis of H9c2 cells was increased while the mitochondrial membrane
      potential was decreased. Compared with the control group, the mRNA levels of
      caspase-3, caspase-9, and cytochrome c all increased with increasing
      concentrations of NaF. In summary, these data suggest that apoptosis is involved
      in NaF-induced H9c2 cell toxicity and that activation of the mitochondrial
      pathway may occur.

PMID- 28494361
TI  - Ferrocene-functionalized graphitic carbon nitride as an enhanced heterogeneous
      catalyst of Fenton reaction for degradation of Rhodamine B under visible light
      irradiation.
AB  - To enhance degradation of Rhodamine B (RhB), a toxic xanthene dye, an iron-doped
      graphitic carbon nitride (CN) is prepared by establishing a covalent bond (-CN-)
      bridging ferrocene (Fc) and CN via a Schiff base reaction. The pi-conjugation
      between the aromatic Fc and CN can be much enhanced by the covalent bond, thereby
      facilitating the bulk-to-surface charge transfer and separation as well as
      reversible photo-redox reactions during photocatalytic reactions. Thus, the
      resulting Fc-CN exhibits a much higher catalytic activity than CN to activate
      hydrogen peroxide (HP) for RhB degradation, because the photocatalytically
      generated electrons from CN can activate HP and effectively maintain the
      bivalence state of Fe in Fc, which also induces the activation of HP. The RhB
      degradation by the Fc-CN activated HP process (Fc-CN-HP) is validated to involve
      OH* by examining the effect of radical probe agent as well as electron
      paramagnetic resonance (EPR) spectroscopic analysis. Fc-CN is also proven to
      activate HP for RhB degradation over multiple times without loss of catalytic
      activity. Through determining the degradation intermediates, RhB is indeed fully
      decomposed by Fc-CN-HP into much lower-molecular-weight organic compounds. These
      features indicate that Fc-functionalization can be an advantageous technique to
      enhance the catalytic activity of CN for activating HP. The results obtained in
      this study are essential to further design and utilize Fc-functionalized CN for
      Fenton-like reactions. The findings shown here, especially the degradation
      mechanism and pathway, are also quite important for treating xanthene dyes in
      wastewater.

PMID- 28494362
TI  - Transformation of carbon tetrachloride and chloroform by trichloroethene
      respiring anaerobic mixed cultures and supernatant.
AB  - Carbon tetrachloride (CT) and chloroform (CF) were transformed in batch reactor
      experiments conducted with anaerobic dechlorinating cultures and supernatant (ADC
      + S) harvested from continuous flow reactors. The Evanite (EV) and
      Victoria/Stanford (VS) cultures, capable of respiring trichloroethene (TCE), 1,2
      cis-dichloroethene (cDCE), and vinyl chloride (VC) to ethene (ETH), were grown in
      continuous flow reactors receiving an influent feed of saturated TCE (10 mM; 60
      mEq) and formate (45 mM; 90 mEq) but no CT or CF. Cells and supernatant were
      harvested from the chemostats and inoculated into batch reactors at the onset of
      each experiment. CT transformation was complete following first order kinetics
      with CF, DCM and CS2 as the measurable transformation products, representing 20
      40% of the original mass of CT, with CO2 likely the unknown transformation
      product. CF was transformed to DCM and likely CO2 at an order of magnitude rate
      lower than CT, while DCM was not further transformed. An analytical first order
      model including multiple key reactions effectively simulated CT transformation,
      product formation and transformation, and provided reasonable estimates of
      transformation rate coefficients. Biotic and abiotic treatments indicated that CT
      was mainly transformed via abiotic processes. However, the presence of live cells
      was associated with the transformation of CF to DCM. In biotic tests both TCE and
      CT were simultaneously transformed, with TCE transformed to ETH and approximately
      15-53% less CF formed via CT transformation. A 14-day exposure to CF (CFmax = 1.4
      MUM) reduced all rates of chlorinated ethene respiration by a factor of 10 or
      greater.

PMID- 28494363
TI  - Reductive solidification/stabilization of chromate in municipal solid waste
      incineration fly ash by ascorbic acid and blast furnace slag.
AB  - Fly ash is a hazardous byproduct of municipal solid waste incineration (MSWI).
      Cementitious material that is based on ground-granulated blast furnace slag
      (GGBFS) has been tested and proposed as a binder to stabilize Pb, Cd, and Zn in
      MSWI fly ash (FA). Cr, however, still easily leaches from MSWI FA. Different
      reagents, such as ascorbic acid (VC), NaAlO2, and trisodium salt nonahydrate,
      were investigated as potential Cr stabilizers. The results of the toxicity
      characteristic leaching procedure (TCLP) showed that VC significantly improved
      the stabilization of Cr via the reduction of Cr(VI) to Cr(III). VC, however,
      could interfere with the hydration process. Most available Cr was transformed
      into stable Cr forms at the optimum VC content of 2 wt%. Cr leaching was strongly
      pH dependent and could be represented by a quintic polynomial model. The results
      of X-ray diffraction and scanning electron microscopy-energy dispersive analysis
      revealed that hollow spheres in raw FA were partially filled with hydration
      products, resulting in the dense and homogeneous microstructure of the solidified
      samples. The crystal structures of C-S-H and ettringite retained Zn and Cr ions.
      In summary, GGBFS-based cementitious material with the low addition of 2 wt% VC
      effectively immobilizes Cr-bearing MSWI FA.

PMID- 28494364
TI  - Novel integrated electrodialysis/electro-oxidation process for the efficient
      degradation of 2,4-dichlorophenoxyacetic acid.
AB  - This work presents a novel approach of wastewater treatment technology that
      consists of a combined electrodialysis/electro-oxidation process, specially
      designed to allow increasing the efficiency in the oxidation of ionic organic
      pollutants contained in diluted waste. Respect to conventional electrolysis, the
      pollutant is simultaneously concentrated and oxidized, enhancing the performance
      of the cell due to the higher concentration achieved in the nearness of the
      anode. A proof of concept is tested with the ionic pesticide 2,4-D (2,4
      dichlorophenoxyacetic acid) and results show that the efficiency of this new
      technology overcomes that electrolysis by more than double, regardless the
      supporting electrolyte used (either NaCl or Na2SO4). Moreover, the removal rate
      of 2,4-D when using NaCl was found to be more efficient, due to the best
      performance of the electrode material selected (DSA(r)) towards the formation of
      oxidants in chloride supporting electrolyte. These results open the way for
      overcoming the efficiency limitations of electrochemical treatment processes for
      the treatment of solutions with low concentrated ionic pollutants.

PMID- 28494365
TI  - A critical review on effects, tolerance mechanisms and management of cadmium in
      vegetables.
AB  - Cadmium (Cd) accumulation in vegetables is an important environmental issue that
      threatens human health globally. Understanding the response of vegetables to Cd
      stress and applying management strategies may help to reduce the Cd uptake by
      vegetables. The aim of the present review is to summarize the knowledge
      concerning the uptake and toxic effects of Cd in vegetables and the different
      management strategies to combat Cd stress in vegetables. Leafy vegetables grown
      in Cd contaminated soils potentially accumulate higher concentrations of Cd,
      posing a threat to food commodities. The Cd toxicity decreases seed germination,
      growth, biomass and quality of vegetables. This reduces the photosynthesis,
      stomatal conductance and alteration in mineral nutrition. Toxicity of Cd toxicity
      also interferes with vegetable biochemistry causing oxidative stress and
      resulting in decreased antioxidant enzyme activities. Several management options
      have been employed for the reduction of Cd uptake and toxicity in vegetables. The
      exogenous application of plant growth regulators, proper mineral nutrition, and
      the use of organic and inorganic amendments might be useful for reducing Cd
      toxicity in vegetables. The use of low Cd accumulating vegetable cultivars in
      conjunction with insolubilizing amendments and proper agricultural practices
      might be a useful technique for reducing Cd exposure in the food chain.

PMID- 28494366
TI  - Aligned copper nanowires as a cut-and-paste exclusive electrochemical transducer
      for free-enzyme highly selective quantification of intracellular hydrogen
      peroxide in cisplatin-treated cells.
AB  - The role and reliable quantification of intracellular hydrogen peroxide during
      cancer therapy constitutes an unexplored and fascinating application. In this
      work, we report the fabrication of vertically aligned copper nanowires (v-CuNWs)
      using electrosynthesis on templates, and their application as a cut-and-paste
      exclusive and flexible electrochemical transducer. This easily adaptable
      electrodic platform is demonstrated for a fast, simple and free-enzyme selective
      quantification of intracellular hydrogen peroxide in Cisplatin-treated human
      renal HK-2 cells. The v-CuNWs sensor was compared with an HRP-enzyme-based
      biosensor showing excellent correlation and indicates the good selectivity and
      analytical performance of the v-CuNWs. This sensing approach opens novel avenues
      for monitoring cell death processes and shows the potential of H2O2 as a cellular
      damage biomarker, with a clear potency for further developments for in vitro
      diagnosis and its implication in cancer therapy.

PMID- 28494367
TI  - Enhanced detection sensitivity of carcinoembryonic antigen on a plasmonic
      nanoimmunosensor by transmission grating-based total internal reflection
      scattering microscopy.
AB  - Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal
      carcinomas and is commonly used as a clinical tumor marker. Enhanced detection
      sensitivity for the assay of CEA molecules was achieved on a plasmonic
      nanoimmunosensor by wavelength-dependent transmission grating (TG)-based total
      internal reflection scattering microscopy (TIRSM). The plasmonic nanoparticles
      were placed in an evanescent field layer on a glass nanoimmunosensor that
      produced evanescent wave scattering by the total internal reflection of light
      from two lasers. The light scattered by target protein (CEA)-bound 20-nm silver
      nanoparticles (plasmonic nanoprobes) was collected and spectrally isolated in
      first-order spectral images (n=+1) by a TG (70 grooves/mm). The combination of
      evanescent wave scattering and TG significantly enhanced the detection
      sensitivity and selectivity due to the minimized spectroscopic interference and
      background noise. The TG-TIRSM method detected the CEA molecules at
      concentrations down to 19.75zM with a wide linear dynamic range of 19.75zM
      39.50nM (correlation coefficient, R=0.9903), which was 45 to 1.25*109 times lower
      than the detection limits and 2*105 to 2*1011 times wider than the dynamic ranges
      of previous assay methods. In particular, by simply changing the antibody of the
      target molecule, this technique can be used to detect various disease-related
      protein biomarkers directly in human biological samples at the single-molecule
      level.

PMID- 28494368
TI  - Metal carbonyl-gold nanoparticle conjugates for highly sensitive SERS detection
      of organophosphorus pesticides.
AB  - The binding of organometallic osmium carbonyl clusters onto the surface of gold
      nanoparticles (10OsCO-Au NPs) greatly enhanced the CO stretching vibration signal
      at ~2100cm-1, which is relatively free from interference due to the absorbance of
      biomolecules. By utilizing the acetylcholinesterase (AChE) mediated hydrolysis of
      acetylthiocholine to thiocholine where the activity of AChE is inhibited by the
      presence of organophosphate pesticides (OPPs), the subsequent thiocholine-induced
      aggregation of 10OsCO-Au NPs can be monitored by the change in color of the NPs
      solution and the variation in intensity of the SERS CO signal. The change in
      color offers a fast pre-screening method, whereas monitoring via SERS is used for
      greater accuracy and lower limit of detection (0.1 ppb) for quantitative
      detection. Its potential as a quick and accurate method of OPPs monitoring in
      consumer products was demonstrated in the detection of OPPs in real spiked
      samples such as beer.

PMID- 28494370
TI  - A novel sensitive sensor for serotonin based on high-quality of AuAg nanoalloy
      encapsulated graphene electrocatalyst.
AB  - A high quality graphene-encapsulated AuAg alloy (AuAg-GR) nanohybrid with
      homogeneous structure and good reproducibility over a desired area was
      successfully fabricated. Taking benefits of the unique architecture, such
      nanohybrid was employed as an efficient electrocatalyst for sensing application.
      The AuAg-GR based sensor could sensitively detected neurotransmitter serotonin (5
      HT) with wide linear detection range (2.7nM to 4.82MUM), very low detection limit
      (1.6nM), negligible interference, and excellent reproducibility. In addition,
      AuAg-GR based sensor accurately determined 5-HT in human serum samples. This is
      due to the enhanced catalytic activity of GR nanosheets-encapsulated AuAg
      nanostructures, which possessed well monodispersion of AuAg alloy, greater
      electrochemical active sites, and good charge transfer possibility. The obtained
      results imply that such nanohybrid is a potential candidate for synthesizing
      electrochemical sensors in requirement of high sensitivity, long-term stability,
      and good reproducibility.

PMID- 28494369
TI  - Lateral flow assay-based bacterial detection using engineered cell wall binding
      domains of a phage endolysin.
AB  - The development of a cost-effective and efficient bacterial detection assay is
      essential for diagnostic fields, particularly in resource-poor settings. Although
      antibodies have been widely used for bacterial capture, the production of soluble
      antibodies is still expensive and time-consuming. Here, we developed a
      nitrocellulose-based lateral flow assay using cell wall binding domains (CBDs)
      from phage as a recognition element and colloidal gold nanoparticles as a
      colorimetric signal for the detection of a model pathogenic bacterium, Bacillus
      cereus (B. cereus). To improve conjugation efficiency and detection sensitivity,
      cysteine-glutathione-S-transferase-tagged CBDs and maltose-binding protein-tagged
      CBDs were produced in Escherichia coli (E. coli) and incorporated in our assays.
      The sensitivity of the strip to detect B. cereus was 1*104 CFU/mL and the overall
      assay time was 20min. The assay showed superior results compared to the antibody
      based approach, and did not show any significant cross-reactivity. This proof of
      concept study indicates that the lateral flow assay using engineered CBDs hold
      considerable promise as simple, rapid, and cost-effective biosensors for whole
      cell detection.

PMID- 28494371
TI  - Improving surface EMG burst detection in infrahyoid muscles during swallowing
      using digital filters and discrete wavelet analysis.
AB  - The visual inspection is a widely used method for evaluating the surface
      electromyographic signal (sEMG) during deglutition, a process highly dependent of
      the examiners expertise. It is desirable to have a less subjective and automated
      technique to improve the onset detection in swallowing related muscles, which
      have a low signal-to-noise ratio. In this work, we acquired sEMG measured in
      infrahyoid muscles with high baseline noise of ten healthy adults during water
      swallowing tasks. Two methods were applied to find the combination of cutoff
      frequencies that achieve the most accurate onset detection: discrete wavelet
      decomposition based method and fixed steps variations of low and high cutoff
      frequencies of a digital bandpass filter. Teager-Kaiser Energy operator, root
      mean square and simple threshold method were applied for both techniques. Results
      show a narrowing of the effective bandwidth vs. the literature recommended
      parameters for sEMG acquisition. Both level 3 decomposition with mother wavelet
      db4 and bandpass filter with cutoff frequencies between 130 and 180Hz were
      optimal for onset detection in infrahyoid muscles. The proposed methodologies
      recognized the onset time with predictive power above 0.95, that is similar to
      previous findings but in larger and more superficial muscles in limbs.

PMID- 28494372
TI  - Separation and preconcentration of riboflavin from human plasma using
      polythionine coated magnetite/hydroxyapatite nanocomposite prior to analysis by
      surfactant-enhanced fluorimetry.
AB  - The exploration of novel adsorption properties of conductive polymers based on
      hybridization with biocompatible nanomaterials receives an increasing interest.
      In this regard, hydroxyapatite (HA) bioceramic is of critical importance mainly
      owing to its facile synthesis, high surface area, economic and low toxicity in
      biological environments. In this work, we first prepared and characterized a
      magnetite/hydroxyapatite (Fe3O4/HA) nanocomposite using the bio-waste chicken
      eggshell via an attractive green way that involved low cost and irrespective of
      toxicity. Then, polythionine as a novel class of conductive polymers was in situ
      coated on the synthesized magnetic bioceramic for the separation and
      preconcentration of riboflavin (vitamin B2) in human plasma before its
      fluorimetric determination. Considering the putative role of riboflavin in
      protecting against cancer and cardiovascular diseases, it is essential to
      evaluate this vitamin in biological fluids. The described method possesses a
      linear range of 0.75-262.5MUgL-1 (R2=0.9985) and a detection limit of 0.20MUgL-1
      (signal-to-noise ratio of 3). The relative standard deviations (RSDs) for single
      sorbent repeatability and sorbent-to-sorbent reproducibility were less than 4.0%
      and 7.6% (n=5), respectively. The respective enrichment factor and extraction
      recovery of the method found to be 35.7 and 98.4%. The analytical performance of
      method for riboflavin was characterized by good consistency of the results with
      those obtained by the enzyme-linked immunosorbent assay (ELISA) conventional
      method (p-value of <0.05). The optimized protocol intended for control
      determinations of riboflavin in human subjects and is addressed to clinical
      laboratories.

PMID- 28494373
TI  - Influence of Li+ charge compensator ion on the energy transfer from Pr3+ to Gd3+
      ions in Ca9Mg(PO4)6F2:Gd3+, Pr3+, Li+ phosphor.
AB  - Phototherapy is a renowned treatment for curing skin diseases since ancient
      times. Phototherapeutic treatment for psoriasis and many other diseases require
      narrow band ultra violet-B (NB-UVB) light with peak intensity at 313nm to be
      exposed to the affected part of body. In this paper, we report combustion
      synthesis of NB-UVB -313nm emitting Ca9Mg(PO4)6F2 phosphors doped with Gd3+, Pr3+
      and Li+ ions. The phase formation was confirmed by obtaining X-ray diffraction
      (XRD) pattern and morphology was studied with the Scanning electron microscopy
      (SEM) images. Photoluminescence (PL) emission spectra show intense narrow band
      emission at 313nm under 274nm excitation wavelengths. Emission intensity was
      enhanced when Ca9Mg(PO4)6F2 compound is co-doped with Pr3+ ions. Excitation
      spectra of Ca9Mg(PO4)6F2:Gd3+, Pr3+ doped samples shows broad excitation in ultra
      violet C (UVC) region. Diffuse reflectance spectra (DRS), obtained by UV-visible
      spectrophotometer, measures the absorption properties of the material. By
      applying Kubelka Munk function on the diffuse reflectance spectra, band gap of
      the material is determined. PL decay curves were examined which indicates
      efficient energy transfer between Pr3+ and Gd3+ ions. Charge compensation effect
      was also studied by co-doping Li+ ion in host. Emission intensity was found to
      increase with the addition of charge compensator. The prepared phosphor has
      potential to convert UVC light into NB-UVB. The luminescence intensity of Gd3+
      shows remarkable increase when it is sensitized with Pr3+, and an addition of
      charge compensator in the form of Li+, show even better results. This phosphor
      surely has the potential to be used as phototherapy lamp phosphor.

PMID- 28494374
TI  - Eigenvalue-eigenvector decomposition (EED) analysis of dissimilarity and
      covariance matrix obtained from total synchronous fluorescence spectral (TSFS)
      data sets of herbal preparations: Optimizing the classification approach.
AB  - The present work compares the dissimilarity and covariance based unsupervised
      chemometric classification approaches by taking the total synchronous
      fluorescence spectroscopy data sets acquired for the cumin and non-cumin based
      herbal preparations. The conventional decomposition method involves eigenvalue
      eigenvector analysis of the covariance of the data set and finds the factors that
      can explain the overall major sources of variation present in the data set. The
      conventional approach does this irrespective of the fact that the samples belong
      to intrinsically different groups and hence leads to poor class separation. The
      present work shows that classification of such samples can be optimized by
      performing the eigenvalue-eigenvector decomposition on the pair-wise
      dissimilarity matrix.

PMID- 28494375
TI  - Thin film assembly of nanosized cobalt(II) bis(5-phenyl-azo-8-hydroxyquinolate)
      using static step-by-step soft surface reaction technique: Structural
      characterization and optical properties.
AB  - Nanosized (NS) cobalt (II) bis(5-phenyl-azo-8-hydroxyquinolate) (NS Co(II)-(5PA
      8HQ)2) thin films have been synthesized using static step-by-step soft surface
      reaction (SS-b-SSR) technique. Structural and optical characterizations of these
      thin films have been carried out using thermal gravimetric analysis (TGA),
      Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), high
      resolution transmission electron microscopy (HR-TEM) and X-ray diffraction (XRD).
      The HR-TEM results revealed that the assembled Co(II)-complex exhibited a
      uniformly NS structure particles in the form of nanorods with width and length up
      to 16.90nm and 506.38nm, respectively. The linear and nonlinear optical
      properties have been investigated. The identified energy gap of the designed thin
      film materials was found 4.01eV. The refractive index of deposited Co(II)-complex
      thin film was identified by thickness-dependence and found as 1.9 at wavelength
      1100nm. In addition, the refractive index was varied by about 0.15 due to an
      increase in the thickness by 19nm.

PMID- 28494376
TI  - Luminescent properties of heterotrinuclear 3d-4f complexes constructed from a
      naphthalenediol-based acyclic bis(salamo)-type ligand.
AB  - Heterotrinuclear 3d-4f complexes with a naphthalenediol-based acyclic bis(salamo)
      type ligand have been synthesized and structurally characterized. Spectral
      titrations clearly show that the heterotrinuclear complexes [Zn2(L)La(OAc)3] (1),
      [Zn2(L)Ce(OAc)3] (2) and [Zn2(L)Dy(OAc)3(CH3OH)].CH2Cl2 (3) are acquired by the
      substitution reaction of the obtained homotrinuclear Zn(II) complex with 1 equiv.
      of Ln(NO3)3 (Ln3+=La3+, Ce3+ and Dy3+). Two Zn(II) ions are penta- and hexa
      coordinated with geometries of distorted tetragonal pyramid and octahedron.
      La(III) ion is deca-coordinated, adopting a distorted bicapped square antiprism
      geometry. Ce(III) ion is nona-coordinated with geometry of distorted capped
      square antiprism as well as Dy(III) ion. The different coordination modes of
      acetate ions in complexes 1, 2 and 3 lead to different coordination numbers of
      the lanthanide(III) ions. Furthermore, the structures and fluorescence properties
      have been discussed.

PMID- 28494377
TI  - Preparation and characterization of electrodeposited SnS:In thin films: Effect of
      In dopant.
AB  - SnS:In thin films were grown on fluorine doped tin oxide (FTO) substrate by
      cathodic electrodeposition technique. The solution was containing 2mM SnCl2 and
      16mM Na2S2O3 and different amounts of 1mM InCl3 as In-dopant. The pH, bath
      temperature, deposition time, and deposition potential (E) were fixed at 2.1, 60
      degrees C, 30min, and -1V, respectively. The XRD results showed that the
      synthesized films were polycrystalline orthorhombic SnS. The XPS results
      demonstrated that the films were composed of Sn, S and In. According to the FESEM
      images, an increase in In-dopant concentration leads to a change in morphology
      from grain-like to sheet-like having a nanoscale thickness of 20-80nm and fiber
      like. The PL spectra of undoped SnS exhibited four emission peaks including a UV
      peak, two blue emission peaks, and an IR emission peak. According to the UV-Vis
      spectra, the direct band gap of SnS:In thin films was estimated to be 1.40
      1.66eV.

PMID- 28494378
TI  - FTIR cryospectroscopic and ab initio studies of desflurane-dimethyl ether H
      bonded complexes.
AB  - The IR spectra of mixtures of desflurane and dimethyl ether are studied with the
      help of FTIR cryospectroscopy in liquefied Kr at T~118-158K. Comparative analysis
      of the experimental data and results of ab initio calculations show that either
      of the two C-H groups of desflurane is involved in heterodimer formation of
      comparable strengths. The blue frequency shift is found for stretching vibrations
      of those C-H donors which directly participate in H-bond formation. Additionally
      the complexes are stabilized by weaker contacts between hydrogen atoms of
      dimethyl ether and fluorine atoms of desflurane.

PMID- 28494379
TI  - Study on molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO,
      QTAIM, HOMO-LUMO energies and docking studies of 5-fluorouracil, a substance used
      to treat cancer.
AB  - Cancer cells can expand to other parts of body through blood system and nodes
      from a mechanism known as metastasis. Due to the large annual growth of cancer
      cases, various biological targets have been studied and related to this disorder.
      A very interesting target related to cancer is human epidermal growth factor
      receptor 2 (HER2). In this study, we analyzed the main intermolecular
      interactions between a drug used in the cancer treatment (5-fluorouracil) and
      HER2. Molecular modeling methods were also employed to assess the molecular
      structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM and HOMO-LUMO
      energies of 5-FU. From the docking simulations it was possible to analyze the
      interactions that occur between some residues in the binding site of HER2 and 5
      FU. To validate the choice of basis set that was used in the NBO and QTAIM
      analyses, theoretical calculations were performed to obtain FT-IR and UV/Vis
      spectra, and the theoretical results are consistent with the experimental data,
      showing that the basis set chosen is suitable. For the maximum lambda from the
      theoretical calculation (254.89nm) of UV/Vis, the electronic transition from HOMO
      to LUMO occurs at 4.89eV. From NBO analyses, we observed interactions between
      Asp863 and 5-FU, i.e. the orbitals with high transfer of electrons are LP O15
      (donor NBO) and BD* (pi) N1-H10 (acceptor NBO), being that the value of this
      interaction is 7.72kcal/mol. Results from QTAIM indicate one main intermolecular
      H bond, which is necessary to stabilize the complex formed between the ligands
      and the biological target. Therefore, this study allowed a careful evaluation on
      the main structural, spectroscopic and electronic properties involved in the
      interaction between 5-FU and HER2, an important biological complex related to the
      cancer treatment.

PMID- 28494380
TI  - A highly sensitive turn-on fluorescent chemosensor for recognition of Zn2+ and
      Hg2+ and applications.
AB  - A fluorescence probe has been designed and synthesized, and applied with a
      combined theoretical and experimental study. Research suggests that the probe can
      be used to sense Zn2+ and Hg2+ through selective turn-on fluorescence responses
      in the aqueous HEPES buffer (0.05M, pH=7.4). The limit of detection (LOD) were
      determined as 1.46*10-7M (Zn2+) and 2.50*10-7M (Hg2+). Moreover, based on DFT,
      the geometry optimizations of probe 1, [1-Hg2+] complex and [1-Zn2+] complex were
      carried out using the Gaussian 09 program, in which the B3LYP function was used.
      The electronic properties of free probe 1 and the metal complexes were studied
      based on the Natural Bond Orbital (NBO) analyses. The probe 1 has also been
      successfully applied to detection of Zn2+ and Hg2+ in living cells.

PMID- 28494381
TI  - Spectroscopic analysis of hot-water- and dilute-acid-extracted hardwood and
      softwood chips.
AB  - Hot-water and dilute sulfuric acid pretreatments were performed prior to chemical
      pulping for silver/white birch (Betula pendula/B. pubescens) and Scots pine
      (Pinus sylvestris) chips to determine if varying pretreatment conditions on the
      original wood material were detectable via attenuated total reflectance (ATR)
      infrared spectroscopy. Pretreatment conditions varied with respect to temperature
      (130 degrees C and 150 degrees C) and treatment time (from 30min to 120min). The
      effects of the pretreatments on the composition of wood chips were determined by
      ATR infrared spectroscopy. The spectral data were compared to those determined by
      common wood chemistry analyses to evaluate the suitability of ATR spectroscopy
      method for rapid detection of changes in the wood chemical composition caused by
      different pretreatment conditions. In addition to determining wood species
      dependent differences in the wood chemical composition, analytical results
      indicated that most essential lignin- and carbohydrates-related phenomena taking
      place during hot-water and acidic pretreatments could be described by applying
      this simple spectral method requiring only a small sample amount and sample
      preparation. Such information included, for example, the cleavage of essential
      lignin bonds (i.e., mainly beta-O-4 linkages in guaiacyl and syringyl lignin) and
      formation of newly condensed lignin structures under different pretreatment
      conditions. Carbohydrate analyses indicated significant removal of hemicelluloses
      (especially hardwood xylan) and hemicelluloses-derived acetyl groups during the
      pretreatments, but they also confirmed the highly resistant nature of cellulose
      towards mild pretreatments.

PMID- 28494382
TI  - A computer-supported management of photographic documentation in plastic surgery 
      System development and its clinical application.
AB  - Photographic documentation is very important for plastic, reconstructive, and
      especially aesthetic surgery procedures. It can be used to improve patient care
      as well as to carry out scientific research. The results of our previous studies
      confirmed a strong demand for Information Technology (IT) systems dedicated to
      plastic surgery. Unfortunately, most of the solutions of this type are not suited
      to the actual needs. For this reason we decided to develop a reliable system for
      photographic documentation storage. The Plastic Reconstructive Esthetic Surgery
      Photo System (PRESsPhoto) was developed and finally deployed in the Plastic,
      Reconstructive and Aesthetic Surgery Clinic of the Medical University in Lodz
      (Poland). Preliminary single-center performance tests proved that the PRESsPhoto
      system is easy to use and provides, inter alia, rapid data search and data entry
      as well as data security. In the future the PRESsPhoto system should be able to
      cooperate with Hospital Information Systems (HIS). The process of development and
      deployment of the PRESsPhoto system is an example of good cooperation between
      health care providers and the informatics, which resulted in a system that meets
      the expectations of plastic surgeons.

PMID- 28494383
TI  - A robust construction algorithm of the centerline skeleton for complex aortic
      vascular structure using computational fluid dynamics.
AB  - Centerlines of blood vessels are useful tools to make important anatomical
      measurements (length, diameter, area), which cannot be accurately obtained using
      2D images. In this paper a brand new method for centerline extraction of vascular
      trees is presented. By using computational fluid dynamics (CFD) we are able to
      obtain a robust and purely functional centerline allowing us to support better
      measurements than classic purely geometrical-based centerlines. We show that the
      CFD-based centerline is within a few pixels from the geometrical centerline where
      the latter is defined (far away from inlet/outlets and from the branches). We
      show that the centerline computed with our method is not affected by traditional
      errors of other classical volume-based algorithms such as topological thinning,
      and could be a potential alternative to be considered for future studies.

PMID- 28494384
TI  - Attentional blink to alcohol cues in binge drinkers versus non-binge drinkers.
AB  - Previous studies have shown alcohol-related attentional biases in social
      drinkers; however, the temporal dynamics of these biases are not well understood.
      The current study examined this issue in 94 participants (27 male) categorized as
      binge drinkers (BD) or non-binge drinkers (NBD). Two versions of an alcohol
      related attentional blink (AB) paradigm were used: one with words and one with
      images. It was predicted that BDs (versus NBDs) would exhibit reduced AB for
      alcohol cues, which would be enhanced for the pictorial version of the task
      (versus words). The relationships between AB and alcohol craving, quantity and
      frequency of alcohol consumption, symptoms of alcohol use disorder, and family
      history of alcohol use disorder (AUD) were also examined. While an AB was
      observed for both alcohol and non-alcohol targets in the NBD group, no AB was
      found for alcohol targets in the BD group. Furthermore, the magnitude of the AB
      was related to drinking, such that higher self-reported hazardous drinking was
      associated with smaller ABs to alcohol-related targets. However, AB was not
      related to craving or family history of AUD. These results suggest that alcohol
      related stimuli are processed more efficiently by BDs, especially those with
      hazardous alcohol consumption patterns. These results may inform treatment and
      prevention efforts targeting binge drinkers.

PMID- 28494385
TI  - L-leucine dietary supplementation modulates muscle protein degradation and
      increases pro-inflammatory cytokines in tumour-bearing rats.
AB  - Cancer cachexia is characterised by involuntary weight loss associated with
      systemic inflammation and metabolic changes. Studies aimed at maintaining lean
      body mass in cachectic tumour-bearing hosts have made important contributions
      reducing the number of deaths and improving the quality of life. In recent years,
      leucine has demonstrated effective action in maintaining lean body mass by
      decreasing muscle protein degradation. Currently, there is a growing need to
      understand how leucine stimulates protein synthesis and acts protectively in a
      cachectic organism. Thus, this study aimed to assess the effects of a leucine
      rich diet on protein degradation signalling in muscle over the course of tumour
      growth. Animals were distributed into four experimental groups, which did or did
      not receive 2*106 viable Walker-tumour cells. Some were fed a leucine-rich diet,
      and the groups were subsequently sacrificed at three different time points of
      tumour evolution (7th, 14th, and 21st days). Protein degradation signals, as
      indicated by ubiquitin-proteasome subunits (11S, 19S, and 20S) and pro- and anti
      inflammatory cytokines, were analysed in all experimental groups. In tumour
      bearing animals without nutritional supplementation (W7, W14, and W21 groups), we
      observed that the tumour growth promoted a concurrent decrease in muscle protein,
      a sharp increase in pro-inflammatory cytokines (TNFalpha, IL-6, and IFNgamma),
      and a progressive increase in proteasome subunits (19S and 20S). Thus, the
      leucine-supplemented tumour-bearing groups showed improvements in muscle mass and
      protein content, and in this specific situation, the leucine-rich diet led to an
      increase on the day in cytokine profile and proteasome subunits mainly on the
      14th day, which subsequently had a modulating effect on tumour growth on the 21st
      day. These results indicate that the presence of leucine in the diet may modulate
      important aspects of the proteasomal pathway in cancer cachexia and may prevent
      muscle wasting due to the decrease in the cachexia index.

PMID- 28494386
TI  - Effect of efferent activation on binaural frequency selectivity.
AB  - Binaural notched-noise experiments indicate a reduced frequency selectivity of
      the binaural system compared to monaural processing. The present study
      investigates how auditory efferent activation (via the medial olivocochlear
      system) affects binaural frequency selectivity in normal-hearing listeners.
      Thresholds were measured for a 1-kHz signal embedded in a diotic notched-noise
      masker for various notch widths. The signal was either presented in phase
      (diotic) or in antiphase (dichotic), gated with the noise. Stimulus duration was
      25 ms, in order to avoid efferent activation due to the masker or the signal. A
      bandpass-filtered noise precursor was presented prior to the masker and signal
      stimuli to activate the efferent system. The silent interval between the
      precursor and the masker-signal complex was 50 ms. For comparison, thresholds for
      detectability of the masked signal were also measured in a baseline condition
      without the precursor and, in addition, without the masker. On average, the
      results of the baseline condition indicate an effectively wider binaural filter,
      as expected. For both signal phases, the addition of the precursor results in
      effectively wider filters, which is in agreement with the hypothesis that
      cochlear gain is reduced due to the presence of the precursor.

PMID- 28494387
TI  - A review of sociocultural factors that may underlie differences in African
      American and European American anxiety.
AB  - Preliminary evidence indicates there may be differences in the prevalence and
      severity of anxiety in African Americans and European Americans. A number of
      sociocultural risk and protective factors have been suggested to contribute to
      these group differences, such as salience of physical illnesses, discrimination,
      stigma toward mental illness, religiosity, and ethnic identity. In this paper,
      the literature concerning each of these factors is reviewed. Overall, the
      strongest evidence was found for ethnic identity and stigma toward mental illness
      as factors underlying group differences in anxiety. Ethnic identity and stigma
      toward mental illness consistently differed by racial group and were associated
      with anxiety in African Americans. Ethnic identity may buffer against the
      negative consequences of anxiety, reducing prevalence rates in African Americans.
      Stigma toward mental illness may decrease African Americans willingness to report
      anxiety symptoms, reducing overall prevalence rates but increasing the severity
      of treated cases. The research regarding discrimination, salience of physical
      illnesses, and religiosity was less clear. Much more research is required, but
      the findings of this review suggest that future studies should put particular
      emphasis on stigma toward mental illness and ethnic identity as important factors
      in understanding African American anxiety outcomes.

PMID- 28494388
TI  - Skills-based childbirth preparation reduces stress for midwives.
AB  - OBJECTIVE: to explore the potential benefits of skills-based childbirth
      preparation on the work related stress levels of midwives. DESIGN: a
      questionnaire was sent out to midwives who had clients participating in an RCT of
      an education package for childbirth preparation (The Pink Kit (PK) Method for
      Birthing Better(r)) delivered to parents. SETTING: midwives were in private
      practice and acted as lead maternity carers to New Zealand first time mothers.
      PARTICIPANTS: one hundred and four independent midwives participated.
      MEASUREMENTS: a brief questionnaire using a Visual Analogue Scale to portray
      perceptions of work-related stress and a yes/no question about expected and/or
      unexpected physical complications. FINDINGS: midwives working with clients in the
      intervention group experienced less work-related stress after correction for
      medical complications compared to the two control groups. KEY CONCLUSIONS:
      working with mothers who have used a programme that increased their childbirth
      self-efficacy decreased the work-related stress experienced by midwives.
      IMPLICATIONS FOR PRACTICE: encouraging pregnant women to develop childbirth
      skills merits further investigation in an effort to reduce the work-related
      stress experienced by midwives.

PMID- 28494389
TI  - Breastfeeding support and opiate dependence: A think aloud study.
AB  - OBJECTIVE: international guidelines recommend the promotion and protection of
      breastfeeding for the substance exposed mother and baby. Yet few studies have
      explored the facilitators, moderators and barriers to successful breastfeeding
      for women enrolled on opiate maintenance treatment, or suggested targeted support
      strategies. The aim of this study was to explore the views of women with opiate
      dependence on proposed elements for inclusion in a breastfeeding support
      intervention. DESIGN: a qualitative study using think aloud technique. SETTING:
      tertiary maternity hospital in the North-East of Scotland. Interviews conducted
      between November 2013 and March 2014. PARTICIPANTS: 6 opiate dependent women
      within 6 months of giving birth. Participants were enrolled on opiate medication
      treatment during their pregnancy, had initiated breastfeeding and accessed in
      hospital breastfeeding support. FINDINGS: an intervention founded on practical,
      informational and environmental elements was endorsed as supportive of continued
      breastfeeding of an infant at risk of Neonatal Abstinence Syndrome. Opiate
      dependent women were more receptive to strategies promoting a person-centered
      approach that were specific to their individualized infant feeding needs and
      delivered within an emotionally supportive environment. Barriers to the
      acceptability of breastfeeding advice included discouraging, prescriptive and
      judgemental healthcare actions and attitudes. KEY CONCLUSIONS: there are distinct
      facilitators, modifiers and barriers to breastfeeding within the context of
      opiate exposure. Using this awareness to underpin the key features of the design
      should enhance maternal receptiveness, acceptability and usability of the support
      intervention. IMPLICATIONS FOR PRACTICE: additional and tailored support
      interventions are required to meet the specific needs of breastfeeding an infant
      experiencing opiate withdrawal. The elimination of disempowering institutional
      actions and attitudes is imperative if a conducive environment in which opiate
      dependent women feel supported is to be achieved.

PMID- 28494390
TI  - Bipolar patients treated with long-acting injectable risperidone in Taiwan: A 1
      year mirror-image study using a national claims database.
AB  - OBJECTIVE: Bipolar disorder (BD) is burdensome for patients and healthcare
      systems. This study evaluated changes in concomitant medication patterns,
      healthcare utilization, and costs after the initiation of risperidone long-acting
      injection (RLAI) treatment among BD patients. METHOD: 287 BD patients receiving
      regular RLAI treatment for 1 year were identified from the Taiwan National Health
      Insurance Research database during 2007-2012. The bootstrapping procedure was
      performed to create 1000 samples to generate normally distributed data. The
      paired t-tests with a correction for multiple comparisons using Bonferroni
      correction were used to compare the proportion of patients of concomitant
      psychiatric medication and resource use and costs between pre- and post-RLAI
      periods. Rapid and non-rapid cycling stratification was performed based on the
      number of change-in-mood episodes within 1 year prior to the index date. RESULTS:
      The mean annual dose of RLAI was 638.41mg, which was equal to an average dose of
      24.6mg every 2 weeks. The prevalence of concomitant use of conventional
      antipsychotics, atypical antipsychotics, lithium, and antidepressants decreased
      from the pre-RLAI period to the post-RLAI period by 23.75%, 31.91%, 1.29%, and
      7.08%, respectively. RLAI use decreased emergency room (ER) visits, hospital
      admissions, length of hospital stay, and non-medication costs (all P<0.0001). The
      cost savings with RLAI were attributed to lower hospitalization costs in spite of
      higher medication costs. Moreover, rapid cycling patients (n=36) demonstrated
      greater reduction in ER and inpatient services with RLAI than non-rapid cycling
      patients (n=251). LIMITATIONS: Of the patients who initiated RLAI, 15% of them
      who had regular treatment were included. Furthermore, data on measures of symptom
      severity, side effects, and hyperprolactinemia were not available. CONCLUSION: BD
      patients had lower inpatient and ER utilization, and non-medication costs after
      using RLAI. In addition, RLAI use decreased the number of change-in-mood episodes
      in rapid cycling patients; which provides additional insights into the treatment
      of rapid cycling BD patients.

PMID- 28494391
TI  - Living with parents or with parents-in-law and postpartum depression: A
      preliminary investigation in China.
AB  - BACKGROUND: Few studies have investigated the association between puerperal
      women's living situation and postpartum depression. The aim of this study was to
      examine the association between living with parents or with parents-in-law and
      postpartum depression among Chinese puerperal women. METHODS: A total of 1126
      participants who completed questionnaire were included in our analysis.
      Postpartum depression status was assessed using the Edinburgh Postnatal
      Depression Scale. Logistic regression models were used to estimate the
      association between living with puerperal women's parents or with parents-in-law
      and risk of postpartum depression after adjustment for potential confounders.
      RESULTS: The prevalence of postpartum depression among participants was 11.8%. Of
      the 1126 participants, 524 (46.5%) lived only with their husbands, 387 (34.4%)
      lived with their parents-in-law, and 215 (19.1%) lived with their parents.
      Compared with those living only with their husbands, puerperal women living with
      their parents-in-law had higher risk of postpartum depression after adjustment
      for potential confounders (OR=2.48; 95% CI: 1.20, 5.15). No association between
      living with puerperal women's parents and postpartum depression was found after
      adjustment for confounders (OR=1.05; 95%CI: 0.42, 2.65). LIMITATIONS: Although we
      adjusted for a wide range of potential confounders, we cannot rule out the
      possibility of residual confounding by other unmeasured factors, such as
      breastfeeding, intimate partner violence, and marital relationship. CONCLUSIONS:
      Our findings suggest that living with parents-in-law may be a risk factor for
      postpartum depression among Chinese puerperal women. Future preventive
      interventions should include strategies that target the puerperal women who lived
      with parents-in-law.

PMID- 28494392
TI  - Opposed effects of hyperthymic and cyclothymic temperament in substance use
      disorder (heroin- or alcohol-dependent patients).
AB  - INTRODUCTION: In the last decade, the comprehension of affective temperaments has
      helped us to outline the boundaries of mood disorders, and to expand our
      knowledge of nosographic areas other than those of affectivity, even if
      affectivity is closely related to them. In the field of substance use disorders,
      the temperamental profile of heroin addicts and alcoholics has been discussed
      elsewhere, but no comparison has yet been made between these two patient
      populations. Such a comparison would help to shed light on the pathogenetic
      mechanisms that link temperament with substance abuse. METHODS: 63 Heroin Use
      Disorder (HUD) and 94 Alcohol Use Disorder (AUD) patients were compared with 130
      healthy controls, with the aim of outlining affective temperament quantity and
      typology according to the formulation of Akiskal and Mallya. RESULTS: Cyclothymic
      temperamental quantity differentiated - both at the univariate and multivariate
      levels - between patients who had various different types of Substance Use
      Disorder, largely irrespective of the principal substance of abuse (heroin or
      alcohol); irritable temperament quantity differentiated HUD patients from AUD
      patients. Hyperthymic temperament typology seemed to be more frequent in healthy
      controls at both univariate and multivariate levels. LIMITATION: Cross-sectional
      study. CONCLUSIONS: Our analyses suggest that cyclothymic temperament quantity
      could best correspond to the temperamental profile of Substance Use Disorder
      patients independently of principal substance of abuse (alcohol or heroin), and
      that irritable temperament quantity may differentiate HUD from AUD patients.
      Hyperthymic temperament typology seemed to be highly protective for HUD and,
      though a bit less, for AUD patients, and was a typical feature of healthy
      controls.

PMID- 28494393
TI  - Alterations in growth, oxidative damage, and metal uptake of five aromatic rice
      cultivars under lead toxicity.
AB  - Lead (Pb) affects plant growth and its related physio-biochemical functions
      negatively. The present study investigated the responses of five different
      fragrant rice cultivars viz., Meixiangzhan (MXZ-2), Xiangyaxiangzhan (XYXZ),
      Guixiangzhan (GXZ), Basmati-385 (B-385), and Nongxiang-18 (NX-18) to four
      different Pb concentrations viz., 0, 400, 800 and 1200 MUM. Results depicted that
      Pb toxicity significantly (P < 0.05) reduced the plant height, tillering ability
      and biomass accumulation by causing oxidative damage to rice plants; nonetheless,
      a significant variation was found in the sensitivity of rice cultivars to Pb
      toxicity. Soluble sugars increased significantly only at 1200 MUM in GXZ and 800
      MUM in B-385, whilst the maximum reductions in protein contents were observed at
      1200 MUM Pb for all rice cultivars. Proline contents were reduced for XYXZ and NX
      18 at Pb1200 MUM. Activities of superoxide dismutase (SOD), peroxidase (POD),
      catalase (CAT) and ascorbate peroxidase (APX) as well as reduced glutathione
      (GSH) and oxidized glutathione (GSSG) showed differential behavior among Pb
      treatments and rice cultivars. Among rice cultivars, GXZ showed better
      antioxidative defense system under Pb toxicity compared with all other cultivars.
      For all rice cultivars, the trend for Pb accumulation was recorded as: roots >
      stems > leaves. Furthermore, significant but negative correlations among Pb
      uptake and plant height (r = -0.79), tillers per plant (r = -0.91) and plant dry
      biomass (r = -0.81) were recorded for all rice cultivars whereas the values of
      translocation factor (TF) from stems to leaves were higher than roots to stems.
      In sum, Pb reduced the early growth and caused physio-biochemical changes in all
      rice cultivars, nonetheless, GXZ proved better able to tolerate Pb stress than
      all other rice cultivars under study.

PMID- 28494394
TI  - Physiological and biochemical changes attenuate the effects of drought on the
      Cerrado species Vatairea macrocarpa (Benth.) Ducke.
AB  - Drought is considered the main abiotic stress because it influences the
      distribution of plant species and limits the productivity of ecosystems. The aim
      of this study was to evaluate the effects of drought on physiological and
      biochemical parameters during the initial development of Vatairea macrocarpa, a
      native cerrado species. Plants were subjected to daily watering (control);
      suppression of watering during 90 days with field capacity (fc) 50% and 25% and
      then followed by rewatering. Relative leaf water content (RWC), gas exchange,
      photosynthetic pigments content, carbohydrate and amino acids content,
      antioxidant activities and growth were recorded. The RWC decreased according to
      the soil water restriction, causing reduction in stomatal conductance and
      decrease of 76.4% in net photosynthesis in plants submitted to 25% fc. Water
      restriction decreased the chlorophyll content, however increased carotenoid
      content and also improved the antioxidant activities of superoxide dismutase
      (SOD), ascorbate peroxidase (APX) and catalase (CAT). In addition, high levels of
      sugars (sucrose, raffinose) and amino acids (proline, tryptophan, valine,
      glutamine and GABA) were detected in drought stressed plants, contributing to
      osmoregulation and as sources of carbon and nitrogen after rehydration. Decreases
      in carbon assimilation promoted a reduction of the leaf area, however an increase
      in the root surface area was observed. After rewatering, the analized parameters
      became similar to the control plants indicating that the severe water stress did
      not impair the survival of young plants. Instead, adjustments were made to
      protect them against drought such as the maintenance of the assimilatory
      metabolism at minimal levels.

PMID- 28494395
TI  - Conformational and vibrational reassessment of solid paracetamol.
AB  - This work provides an answer to the urge for a more detailed and accurate
      knowledge of the vibrational spectrum of the widely used analgesic/antipyretic
      drug commonly known as paracetamol. A comprehensive spectroscopic analysis -
      including infrared, Raman, and inelastic neutron scattering (INS) - is combined
      with a computational approach which takes account for the effects of
      intermolecular interactions in the solid state. This allows a full reassessment
      of the vibrational assignments for Paracetamol, thus preventing the propagation
      of incorrect data analysis and misassignments already found in the literature. In
      particular, the vibrational modes involving the hydrogen-bonded NH and OH groups
      are correctly reallocated to bands shifted by up to 300cm-1 relatively to
      previous assignments.

PMID- 28494396
TI  - A comparative study of the spectral, fluorometric properties and photostability
      of natural curcumin, iron- and boron- complexed curcumin.
AB  - Curcumin is a yellow phenolic compound with a wide range of reported biological
      effects. However, two main obstacles hinder the use of curcumin therapeutically,
      namely its poor bioavailability and photostability. We have synthesized two
      curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an
      iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence
      efficiency (quantum yield) and greater photostability in solution. The improved
      photostability could be attributed to the coordination structures and the removal
      of beta-diketone group from curcumin. The fluorescence and ultra violet/visible
      absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral
      pattern when dissolved in the same organic solvent. However, a shift towards a
      lower wavelength was observed when moving from polar to non-polar solvents,
      possibly due to differences in solvent polarity. A plot of Stokes' shift vs the
      orientation polarity parameter (Deltaf) or vs the solvent polarity parameter (ET
      30) showed an improved correlation between the solvent polarity parameter than
      with the orientation polarity parameter and indicating that the red shift
      observed could be due to hydrogen-bonding between the solvent molecules. A
      similar association was obtained when Stokes' shift was replaced by maximum
      synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than
      curcumin, suggesting they may be good candidates for medical imaging and in vitro
      studies.

PMID- 28494397
TI  - Bioaccumulation and elimination of bisphenol a (BPA) in the alga Chlorella
      pyrenoidosa and the potential for trophic transfer to the rotifer Brachionus
      calyciflorus.
AB  - In this study, we investigated the bioaccumulation and elimination of 14C-labeled
      BPA by the green alga Chlorella pyrenoidosa and the subsequent transfer of 14C
      BPA residues from the contaminated alga to the rotifer Brachionus calyciflorus.
      After 10 days of BPA exposure, the algal cells accumulated 15% of the initial
      radioactivity from the medium, with 71% of the accumulated radioactivity
      occurring in the form of non-extractable bound residues. An approximate steady
      state of the accumulation of the 14C-BPA residues in the algae was reached after
      about 4 days of exposure. The bioconcentration factor of total radioactivity in
      the algae was 106 mL (g dry weight)-1 at steady state. During the elimination
      phase, only the extractable residues were released from the algae into the water
      whereas the bound residues, following their ingestion by the rotifers, were
      converted to extractable forms and then also released. Furthermore, our results
      demonstrated the biomagnification of BPA-related residues in the food chain
      between algae and rotifers. The trophic transfer of these BPA-derived residues
      from the algae to rotifers and thus the environmental hazard may posed by this
      pathway, because of subsequent effects on the food chain.

PMID- 28494398
TI  - Oil uptake by plant-based sorbents and its biodegradation by their naturally
      associated microorganisms.
AB  - The plant waste-products, wheat straw, corn-cobs and sugarcane bagasse took up
      respectively, 190, 110 and 250% of their own weights crude oil. The same
      materials harbored respectively, 3.6 * 105, 8.5 * 103 and 2.3 * 106 g-1 cells of
      hydrocarbonoclastic microorganisms, as determined by a culture-dependent method.
      The molecular, culture-independent analysis revealed that the three materials
      were associated with microbial communities comprising genera known for their
      hydrocarbonoclastic activity. In bench-scale experiments, inoculating oily media
      with samples of the individual waste products led to the biodegradation of 34.0
      44.9% of the available oil after 8 months. Also plant-product samples, which had
      been used as oil sorbents lost 24.3-47.7% of their oil via their associated
      microorganisms, when kept moist for 8 months. In this way, it is easy to see that
      those waste products are capable of remediating spilled oil physically, and that
      their associated microbial communities can degrade it biologically.

PMID- 28494399
TI  - Comparative toxic responses of male and female lizards (Eremias argus) exposed to
      (S)-metolachlor-contaminated soil.
AB  - Soil contamination caused by the widespread use of pesticides is one of the main
      environmental problems facing conservation organizations. (S)-metolachlor (SM) is
      a selective pre-emergent herbicide that poses potential risks to soil-related
      organisms such as reptiles. The present study elucidated the toxic effects of SM
      (3 and 30 mg/kg soil weight) in Eremias argus. The results showed that growth
      pattern was similar between the sexes in breeding season. For males, both kidney
      coefficient (KC) and testis coefficient in the exposure group were significantly
      different from those in the control group, while only KC in the high-dose group
      was significantly higher for females. Based on histopathological analysis, the
      livers of female lizards were more vulnerable than those of males in the exposure
      group. A reduction in total egg output was observed in SM exposed lizards.
      Accumulation studies indicated that skin exposure may be an important route for
      SM uptake in E. argus, and that the liver and lung have strong detoxification
      abilities. In addition, the body burdens of the lizards increased with increasing
      SM concentration in the soil.

PMID- 28494400
TI  - Maternal serum lead level during pregnancy is positively correlated with risk of
      preterm birth in a Chinese population.
AB  - Lead (Pb) is a well-known developmental toxicant. The aim of the present study
      was to analyze the association between maternal serum Pb level and risk of
      preterm birth in a population-based birth cohort study. The present study
      analyzed a sub-study of the China-Anhui Birth Cohort that recruited 3125 eligible
      mother-and-singleton-offspring pairs. Maternal serum Pb level was measured by
      graphite furnace atomic absorption spectrometry. All subjects were classified
      into three groups by tertile division according to serum Pb level: Low-Pb (L-Pb,
      <1.18 MUg/dl), Medium-Pb (M-Pb, 1.18-1.70 MUg/dl), and High-Pb (H-Pb, >=1.71
      MUg/dl). The rate of preterm birth was 2.8% among subjects with L-Pb, 6.1% among
      subjects with M-Pb, and 8.1% among subjects with H-Pb, respectively. After
      controlling confounding factors, the adjusted OR for preterm birth was 2.33
      (95%CI: 1.49, 3.65) among subjects with M-Pb and 3.09 (95%CI: 2.01, 4.76) among
      subjects with H-Pb. Of interest, maternal Pb exposure in early gestational stage
      than in middle gestational stage was more susceptible to preterm birth. Moreover,
      maternal serum Pb level was only associated with increased risk of late preterm
      birth. The present study provides evidence that maternal serum Pb level during
      pregnancy is positively associated with risk of preterm birth in a Chinese
      population.

PMID- 28494401
TI  - Using two-dimensional correlation size exclusion chromatography (2D-CoSEC) to
      explore the size-dependent heterogeneity of humic substances for copper binding.
AB  - Knowledge of the heterogeneous distribution of humic substances (HS) reactivities
      along a continuum of molecular weight (MW) is crucial for the systems where the
      HS MW is subject to change. In this study, two dimensional correlation
      spectroscopy combined with size exclusion chromatography (2D-CoSEC) was first
      utilized to obtain a continuous and heterogeneous presence of copper binding
      characteristics within bulk HS with respect to MW. HS solutions with varying
      copper concentrations were directly injected into a size exclusion chromatography
      (SEC) system with Tris-HCl buffer as a mobile phase. Several validation tests
      confirmed neither structural disruption of HS nor competition effect of the
      mobile phase used. Similar to batch systems, fluorescence quenching was observed
      in the chromatograms over a wide range of HS MW. 2D-CoSEC maps of a soil-derived
      HS (Elliot soil humic acid) showed the greater fluorescence quenching degrees
      with respect to the apparent MW on the order of 12500 Da > 10600 Da > 7000 Da >
      15800 Da. The binding constants calculated based on modified Stern-Volmer
      equation were consistent with the 2D-CoSEC results. More heterogeneity of copper
      binding affinities within bulk HS was found for the soil-derived HS versus an
      aquatic HS. The traditional fluorescence quenching titration method using
      ultrafiltered HS size fractions failed to delineate detailed distribution of the
      copper binding characteristics, exhibiting a much shorter range of the binding
      constants than those obtained from the 2D-CoSEC. Our proposed technique
      demonstrated a great potential to describe metal binding characteristics of HS at
      high MW resolution, providing a clear picture of the size-dependent metal-HS
      interactions.

PMID- 28494402
TI  - Polycyclic aromatic hydrocarbons in ocean sediments from the North Pacific to the
      Arctic Ocean.
AB  - Eighteen polycyclic aromatic hydrocarbons (PAHs) were measured in surficial
      sediments along a marine transect from the North Pacific into the Arctic Ocean.
      The highest average Sigma18PAHs concentrations were observed along the
      continental slope of the Canada Basin in the Arctic (68.3 +/- 8.5 ng g-1 dw),
      followed by sediments in the Chukchi Sea shelf (49.7 +/- 21.2 ng g-1 dw) and
      Bering Sea (39.5 +/- 11.3 ng g-1 dw), while the Bering Strait (16.8 +/- 7.1 ng g
      1 dw) and Central Arctic Ocean sediments (13.1 +/- 9.6 ng g-1 dw) had relatively
      lower average concentrations. The use of principal components analysis with
      multiple linear regression (PCA/MLR) indicated that on average oil related or
      petrogenic sources contributed ~42% of the measured PAHs in the sediments and
      marked by higher concentrations of two methylnaphthalenes over the non-alkylated
      parent PAH, naphthalene. Wood and coal combustion contributed ~32%, and high
      temperature pyrogenic sources contributing ~26%. Petrogenic sources, such as oil
      seeps, allochthonous coal and coastally eroded material such as terrigenous
      sediments particularly affected the Chukchi Sea shelf and slope of the Canada
      Basin, while biomass and coal combustion sources appeared to have greater
      influence in the central Arctic Ocean, possibly due to the effects of episodic
      summertime forest fires.

PMID- 28494403
TI  - HER2 status predicts for upfront AI benefit: A TRANS-AIOG meta-analysis of 12,129
      patients from ATAC, BIG 1-98 and TEAM with centrally determined HER2.
AB  - BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within
      the first 2-3 years of adjuvant endocrine therapy, has the potential to inform
      patient selection for upfront aromatase inhibitor (AI) therapy or switching
      strategy tamoxifen followed by AI. The pre-existing standardisation of
      methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization)
      facilitates analysis of existing data for this key marker. METHODS: Following a
      prospectively designed statistical analysis plan, patient data from 3 phase III
      trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast
      International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre
      Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant
      endocrine treatment were collected and a treatment-by-marker analysis of distant
      recurrence-free interval-censored at 2-3 years treatment - for HER2 status * AI
      versus tamoxifen treatment was performed to address the clinical question
      relating to efficacy of 'upfront' versus 'switch' strategies for AIs. RESULTS: A
      prospectively planned, patient-level data meta-analysis across 3 trials
      demonstrated a significant treatment (AI versus tamoxifen) by marker (HER2)
      interaction in a multivariate analysis; (interaction hazard ratio [HR] = 1.61,
      95% CI 1.01-2.57; p < 0.05). Heterogeneity between trials did not reach
      statistical significance. The HER2 negative (HER2-ve) group gained greater
      benefit from AI versus tamoxifen (HR = 0.70, 95% CI 0.56-0.87) than the HER2
      positive (HER2+ve) group (HR = 1.13, 95% CI 0.75-1.71). However, the small number
      of HER2+ve cases (n = 1092 across the 3 trials) and distant recurrences (n = 111)
      may explain heterogeneity between trials. CONCLUSIONS: A patient-level data meta
      analysis demonstrated a significant interaction between HER2 status and treatment
      with AI versus tamoxifen in the first 2-3 years of adjuvant endocrine therapy.
      Patients with HER2-ve cancers experienced improved outcomes (distant relapse)
      when treated with upfront AI rather than tamoxifen, whilst patients with HER2+ve
      cancers fared no better or slightly worse in the first 2-3 years. However, the
      small number of HER2+ve cancers/events may explain a large degree of
      heterogeneity in the HER2+ve groups across all 3 trials. Other causes, perhaps
      related to subtle differences between AIs, cannot be excluded and warrant further
      exploration.

PMID- 28494404
TI  - Treatment and pattern of bone metastases in 1094 patients with advanced breast
      cancer - Results from the prospective German Tumour Registry Breast Cancer cohort
      study.
AB  - A high proportion of patients with breast cancer develop bone metastases, yet
      data on routine treatment with bone-targeted agents (BTA) are rare. We report
      real-life outcome data of patients with breast cancer metastasised to the bone
      treated by office-based oncologists in Germany. The ongoing, prospective,
      multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK)
      was started in 2007 in 140 centres across Germany. This interim analysis of 1094
      patients with bone metastases revealed differences among the tumour subtypes: at
      start of first-line therapy, 36% of the patients with hormone receptor (HR)
      positive and only 20% of the patients with HR-negative tumours presented with
      bone-only metastasis. The majority of patients with bone metastases (89%, n =
      976) received BTA therapy. In 2014-2015, 37% of the patients received the
      bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of
      BTA therapy was 20 months (interquartile range 31.5 months), starting a median of
      3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before
      death. The median overall survival (OS) also varied among the types of metastasis
      at start of first-line therapy ranging from 54 months (95% confidence interval
      [CI] 37.6-70.8), 38 months (95% CI 29.4-44.2) to 28 months (95% CI 24.2-31.0) for
      patients with bone-only metastases, non-visceral with or without bone metastases
      and visceral with or without bone metastases respectively. We show that choice
      and duration of BTA therapies are in conformity with guidelines applicable in
      Germany. To our knowledge, this is the first presentation of data on incidence,
      metastatic pattern, treatment and survival of patients with bone metastases in
      routine practice.

PMID- 28494405
TI  - Radical treatment of oligometastatic non-small cell lung cancer: Ready for prime
      time?
AB  - Oligometastatic non-small cell lung cancer (NSCLC), defined as a disease with low
      metastatic burden and limited organ involvement, is conceived as an intermediate
      condition between a truly localised disease and a widely metastatic tumour.
      Traditionally, local ablative therapies (LATs), such as surgery and radiotherapy,
      have been limited to symptoms' palliation in advanced NSCLC. Several
      retrospective studies suggest that using local ablative therapy for
      oligometastatic disease could offer good local control of the disease and
      improvement in terms of progression-free survival. The first randomised study of
      local consolidative therapy versus maintenance therapy or observation in
      oligometastatic NSCLC has been recently published. The results of this phase II
      trial showed an impressive improvement in median progression-free survival with
      local therapy and a delay in the appearance of new lesions, suggesting a
      systemically extended benefit of consolidation therapies. Nevertheless, further
      confirmation of this evidence with additional future trials is needed to
      definitively consider the combination of local treatment techniques with novel
      systemic agents recently approved for NSCLC therapy, such as immune checkpoint
      inhibitors.

PMID- 28494406
TI  - Relative dose intensity as a proxy measure of quality and prognosis in adjuvant
      chemotherapy for breast cancer in daily clinical practice.
AB  - AIM: Adjuvant chemotherapy treatment of women with breast cancer is frequently
      complicated by toxic side-effects, resulting in dose reduction and delay. In
      Dutch guidelines, a relative dose intensity (RDI) of at least 85% is recommended
      for optimal treatment. The aim was to investigate predictors of low RDI and its
      effect on prognosis. METHODS: All patients treated in the St. Antonius Hospital
      with adjuvant chemotherapy for breast cancer between 2008 and 2013 were included
      (N = 605). RDI was calculated for each single chemotherapeutic agent and for
      chemotherapy regimens in total. Incidence and causes of RDI <85% were studied, as
      well as the effect of RDI on prognosis. RESULTS: About 10% of 605 patients had
      RDIs <85%. Predictive factors included age, episodes of febrile neutropenia and
      grade III or IV hypersensitivity reaction to taxanes. Other adverse events, such
      as peripheral neuropathy, did not affect RDI. The incidence of febrile
      neutropenia in the 5-fluorouracil, epirubicin, cyclofosfamide, docetaxel (FEC-D)
      protocol was 24% and therefore was above the threshold set by the European
      Organisation for Research and Treatment of Cancer for primary granulocyte colony
      stimulating factor (G-CSF) prophylaxis. No relationship between RDI and (disease
      free) survival was found with a median follow-up of 38 months. Apart from the
      stage of disease, obesity is a predictor of poor outcome. CONCLUSIONS: RDI <85%
      is predicted by patients' age, febrile neutropenia and hypersensitivity reactions
      to taxanes. The incidence of febrile neutropenia in FEC-D treatment indicates
      primary prophylaxis with G-CSF following docetaxel treatment. No relationship was
      found between RDI and (disease-free) survival, but longer follow-up is needed.

PMID- 28494407
TI  - Streptococcus mutans membrane lipid composition: Virulence factors and structural
      parameters.
AB  - OBJECTIVE: The aim of the present work was to analyze whether the location of the
      dental biofilm was associated with shifts in the membrane fatty acid profile, and
      whether such shifts could affect certain virulence factors of strains of
      Streptococcus mutans. DESIGN: An experimental study was conducted to assess the
      behavior of S. mutans strains isolated from dental biofilm collected from sound
      and carious smooth and occlusal surfaces of the oral cavity of children. The
      lipid composition of the bacterial membrane, structural membrane parameters, acid
      survival, and ATPase activity were tested at pH 7 and 5. RESULTS: At pH 5, an
      increase in both the unsaturated and the long chain fatty acids as well as in
      proton ATPase hydrolytic activity was observed in strains isolated from carious
      smooth surface biofilm but not in carious occlusal surface strains. The observed
      changes correlated with the studied structural parameters, and were found to be
      associated with membrane organization. The changes correlated with a decreased in
      DeltaC (sn-1 and sn-2 acyl chain inequivalence), indicative of increased acyl
      chain interaction. CONCLUSIONS: The obtained results suggest that the acidic
      environment (pH 5) of smooth surface caries affects membrane organization,
      inducing a shift in membrane lipid profile, which would likely induce better
      protein/lipid hydrophobic matching, resulting in increased ATPase activity and
      higher acid survival.

PMID- 28494408
TI  - Solubilisation of oils in aqueous solutions of a random cationic copolymer.
AB  - HYPOTHESIS: Reports of random copolymers capable of solubilising hydrophobic oils
      are rare. This is primarily because random copolymers are unlikely to self
      assemble into suitable aggregates (or micelles) in water. A random copolymer with
      a "blocky" (or lumpy) microstructure may have potential to solubilise hydrophobic
      oils in water. This type of polymer would have advantages over block copolymers
      which are more laborious and costly to synthesise. EXPERIMENTS: The solubilising
      capacity of a blocky random copolymer, namely poly(methyl methacrylate-co-2
      dimethylaminoethyl methacrylate) (PMMA-co-PDMAEMA) is assessed by UV-visible
      spectroscopy and compared with common reference surfactants. The relative
      solubilising performance of random copolymers (across a narrow range of DMAEMA
      mol % fraction) for aromatic and aliphatic oils was also studied. The morphology
      of the aggregates was monitored as a function of the solubilisation capacity by
      small-angle neutron scattering (SANS) and dynamic-light scattering (DLS).
      FINDINGS: Similarly to well-defined block copolymers, these random copolymers
      have a specific preference for solubilising aromatic over aliphatic oils.
      Increasing hydrophobicity of the copolymer enhances the solubilisation capacity.
      SANS has highlighted that aggregates become swollen and more uniform/spherical
      with increasing concentration of aromatic solubilisate, and that the aromatic
      solubilisate partitions throughout the random copolymer aggregates.

PMID- 28494409
TI  - Effect of alkaline pretreatment on mesophilic and thermophilic anaerobic
      digestion of a submerged macrophyte: Inhibition and recovery against dissolved
      lignin during semi-continuous operation.
AB  - The long-term effect of alkaline pretreatment on semi-continuous anaerobic
      digestion (AD) of the lignin-rich submerged macrophyte Potamogeton maackianus was
      investigated using mesophilic and thermophilic conditions. In pretreated
      reactors, dissolved lignin accumulated to high levels. CH4 production under the
      pretreated condition was higher than that of the untreated condition, but
      decreased from Days 22 (mesophilic) and 42 (thermophilic). However, CH4
      production subsequently recovered, although dissolved lignin accumulated.
      Further, the change in the microbial community was observed between conditions.
      These results suggest that dissolved lignin temporarily inhibited AD, although
      acclimatization to dissolved lignin occurred during long-term operation. During
      the steady state period, mesophilic conditions achieved a 42% increase in the CH4
      yield using pretreatment, while thermophilic conditions yielded an 8% increment.
      Because volatile fatty acids accumulated even after acclimatization during the
      thermophilic pretreated condition and was discharged with the effluent,
      improvement of the methanogenic step would enable enhanced CH4 recovery.

PMID- 28494410
TI  - Carboxylic acid functionalized sesame straw: A sustainable cost-effective
      bioadsorbent with superior dye adsorption capacity.
AB  - This study prepared a carboxylic functionalized bioadsorbent that met the "4-E"
      criteria: Efficient, Economical, Environmentally friendly, and Easily-produced.
      Sesame straw (Sesamum indicum L.) was functionalized through treatment with
      citric acid (SSCA) and tartaric acid (SSTA). The products were examined for
      adsorption capacity and mechanisms. Langmuir model gave the best fit for the
      isotherm data, and the maximum monolayer adsorption capacity of SSCA was 650mgg-1
      for methylene blue (MB). The excellent dye adsorption capacity of SSCA can be
      attributed to the introduction of ester groups during citric-acid modification
      and the tube-like structures (i.e., sesame straw cell wall remnants). At last,
      the cost of carboxylic acid functionalized bioadsorbents was evaluated, which
      showed that SSCA would be the most cost-effective bioadsorbent. Additionally,
      this study presents a thermo-decomposition methodology for contaminant-loaded
      bioadsorbent. Results showed that SSCA is probably one of the few bioadsorbents
      that can be produced and applied in industrial scale.

PMID- 28494411
TI  - Deep eutectic solvents' ability to solubilize lignin, cellulose, and
      hemicellulose; thermal stability; and density.
AB  - An environmentally-friendly method to separate cellulose and hemicelluloses from
      lignin in recalcitrant biomass for subsequent conversion is desirable to reduce
      greenhouse gas generation. Easily-prepared, deep eutectic solvents (DESs) have
      low volatility, wide liquid range, non-flammability, nontoxicity,
      biocompatibility, and biodegradability. This study shows the DESs (formic
      acid:choline chloride, lactic acid:choline chloride, acetic acid:choline
      chloride, lactic acid:betaine, and lactic acid:proline) to be capable of
      preferentially dissolving lignin at 60 degrees C. Thermogravimetric analysis show
      DES to be stable at typical biomass processing temperatures. Pretreating loblolly
      pine in one DES increased glucose yield after enzymatic hydrolysis to more than
      seven times that of raw or glycerol-pretreated pine. The density of DES
      pretreated biomass was found to be 40% higher than the untreated pine's density.

PMID- 28494412
TI  - Long-term reliability and stability of behavioral measures among adolescents: The
      Delay Discounting and Stroop tasks.
AB  - Delay Discounting (DD) and the Stroop test are two fundamental tasks for the
      assessment of impulsivity and inhibitory control, core features of several
      behavioral disorders. Although the study of reliability and temporal stability is
      important, only studies with adults and small samples have been carried out. The
      aim of this study is to assess the one-year reliability and temporal stability of
      both tasks among adolescents. A total of 1375 adolescents (M = 13.08 years old,
      SD = 0.51) made up the final sample (53.5% males). The results showed moderate
      stability and good reliability for both DD (alpha = 0.90) and Stroop (alpha =
      0.85). Indices based on the reaction times and not the number of errors are
      recommended when using the Stroop test. These results support the use of both
      behavioral tasks in longitudinal research among adolescents.

PMID- 28494414
TI  - Relationship violence victimization and binge drinking trajectories among a
      nationally representative sample of adolescents.
AB  - The present study evaluated the impact of relationship violence (RV)
      victimization on the longitudinal trajectory of binge drinking (BD) among 3614 US
      adolescents (51.2% male) who participated in an initial telephone interview
      regarding physical and sexual RV victimization and binge drinking. Two follow-up
      phone interviews were completed over approximately three years. Multilevel
      modeling revealed small, but significant, increases in BD over time; older
      adolescents and those who had ever experienced RV victimization were more likely
      to report BD at Wave 1 compared to younger adolescents and non-victims. Although
      new RV victimization reported during the study predicted an increase in the
      likelihood of BD at that occasion, those who had ever experienced RV
      victimization were less likely to report BD over time compared to non-victims.
      Contrary to expectations, no sex differences emerged. Findings indicate that BD
      may precede RV. Interventions to reduce alcohol-related RV may be especially
      useful in this population.

PMID- 28494413
TI  - Household chaos as a context for intergenerational transmission of executive
      functioning.
AB  - Executive functioning (EF) may be transmitted across generations such that
      strengths or deficiencies in parent EF are similarly manifested in the child. The
      present study examined the contributions of parent EF and impulsivity on
      adolescent EF, and investigated whether household chaos is an environmental
      moderator that alters these transmission processes. American adolescents (N =
      167, 47% female, 13-14 years old at Time 1) completed behavioral measures of EF
      and reported household chaos at Time 1 and one year later at Time 2. Parents
      completed behavioral measures of EF and self-reported impulsivity at Time 1.
      Results indicated that lower parent EF at Time 1 predicted lower adolescent EF at
      Time 2 (controlling for adolescent EF and IQ at Time 1), but only in the context
      of high household chaos. Findings suggest that household chaos may be a risk
      factor that compounds influences of poor parent EF and compromises adolescent EF
      development.

PMID- 28494415
TI  - Studies on curative efficacy of monoterpene eugenol on anti- leukemic drug
      arsenic trioxide induced cardiotoxicity.
AB  - BACKGROUND: Arsenic trioxide (As2O3) is emerging as a frontline agent for the
      treatment of acute promyelocytic leukemia (APL) but the therapeutic application
      is limited by its toxicity. QT prolongation, torsades de pointes and sudden
      cardiac death have been implicated in the As2O3 therapy. So eugenol is a
      monoterpene compound is well known for its antioxidant properties and protective
      effect on the cardiovascular system. OBJECTIVE: In this study, the
      cardioprotective effect of eugenol on cardiac electrical conductivity, tissue
      electrolytes, myocardial markers, antioxidant system, lipid peroxidation and
      nitric oxide production was investigated in male Wistar rats treated with arsenic
      trioxide. RESULTS: The Inductively coupled plasma emission spectroscopic (ICP
      OES) analysis pointed out the accumulation of arsenic in heart tissue. The rats
      administered with arsenic trioxide (4mg/kg body wt) exhibited myocardial damage
      that was manifested by the elevation of cardiac markers (LDH, CK-MB) enzymes and
      deterioration in the antioxidant enzymes (GSH, GST, GPx). Combination treatment
      with eugenol (5mg/kg of body wt) upholds the tissue antioxidant level, Na+/K+ -
      ATPase and Ca2+- ATPase activity and brings the cytosolic Ca2+, K+ and Na +
      levels near to normal value. Conjoined therapy with eugenol ameliorated the
      membrane peroxidation, restored the normal heart rate and rectified the
      prolongation of QT interval in the electrocardiogram. Histological examination of
      cardiac segments also supported the beneficial role of eugenol against arsenic
      induced oxidative damages. CONCLUSION: Our in vivo experimental findings suggest
      that monoterpenoid eugenol could be a potent and novel cytoprotective agent of
      clinical application against As2O3 induced cardiotoxicity.

PMID- 28494416
TI  - Ameliorative effect of vitamin E and selenium against oxidative stress induced by
      sodium azide in liver, kidney, testis and heart of male mice.
AB  - The study purported to define the effects of daily administration of vitamin E
      (Vit E) and selenium (Se) on antioxidant enzyme activity in mice treated with
      high doses of sodium azide (SA). Male mice were randomly split into nine groups.
      Groups 1, 2 and 3 were injected daily with saline, Vit E, and Se, respectively,
      while groups 4, 5 and 6 administrated with different doses of SA (low, medium and
      high, respectively). The mice in groups 7, 8 and 9 received 100mg/kg Vit E,
      17.5mg/kg Se, and a combination of Vit E and Se, respectively before the SA
      treatment. Hepatic, renal, testis and heart, antioxidant enzymes as well as
      levels of lipid peroxidation and total antioxidant capacity levels were
      determined. Vit E alone affected on the antioxidant parameters of the examined
      tissues. Se had a preventive effect on the decrease of antioxidant parameters
      caused by SA and improved the diminished activities of all of them. The study
      demonstrates that a high dose of SA may alter the effects of normal level
      antioxidant/oxidative status of male mice and that Se is effective in reducing
      the SA-damage. Se acts as a synergistic agent with the effect of Vit E in various
      damaged caused by SA.

PMID- 28494417
TI  - The role of free kappa and lambda light chains in the pathogenesis and treatment
      of inflammatory diseases.
AB  - Kappa (kappa) or lambda (lambda) free light chains (FLCs) are produced from B
      cells during immunoglobulin synthesis. FLCs have been shown to participate in
      several key processes of immune responses. They are necessary to adjust PMN
      functions and assist PMN pre-stimulation. Moreover, they cause mast cell
      degranulation which releases pro-inflammatory mediators and stimulates local
      inflammatory responses in some conditions such as inflammatory bowel disease
      (IBD). Having low molecular weights which may straightly be toxic to proximal
      tubule cells (PTCs), FLCs can also have an important role in renal diseases. In
      this review we have highlighted the involvement of light chains in the
      pathogenesis of some inflammatory diseases and discussed their potential to be
      the targets of therapeutic purposes.

PMID- 28494418
TI  - Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and
      oxidative stress induced by mercuric chloride in male rats: A protective
      approach.
AB  - Mercury toxicity is an emerging problem in the world as its concentration is
      rising continuously due to increased industrial, medicinal and domestic uses.
      Exposure to mercury represents a serious challenge to humans and other living
      biomes. The aim of the present study was to assess the protective effect of
      natural products as Zingiber officinale extract and its active compound (6
      gingerol) against mercuric chloride-induced hepatorenal toxicity and oxidative
      stress in male rats. Male Sprague-Dawley rats (150+/-10g, n=6 per group) were
      administered HgCl2 (12MUmol/kg, ip; once only) the treatment of Zingiber
      officinale Rosc. extract (ZO: 125mg/kg, po) and 6-gingerol (GG: 50mg/kg, po) for
      three days after 24h of HgCl2 administration. Acute HgCl2 administration altered
      various biochemical parameters, including transaminases, alkaline phosphatase,
      lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and
      cholesterol, urea, creatinine, uric acid and blood urea nitrogen contents with a
      concomitant decline in protein and albumin concentration in serum. In addition, a
      significant rise in lipid peroxidation level with concomitant decrease in reduced
      glutathione content and the antioxidant enzymes activities of superoxide
      dismutase, catalase, glutathione reductase, glutathione peroxidase and
      glutathione-S-transferase after acute HgCl2 exposure. Results of the present
      investigation clearly showed that both treatments as Zingiber officinale extract
      and 6-gingerol provide protection against acute mercuric chloride-intoxication by
      preventing oxidative degradation of a biological membrane from metal mediated
      free radical attacks. Biochemical data were well supported by histopathological
      findings. In conclusion, natural products may be an ideal choice against
      oxidative damage induced by mercury poisoning.

PMID- 28494419
TI  - Neuroprotective effects of total flavonoid fraction of the Epimedium koreanum
      Nakai extract on dopaminergic neurons: In vivo and in vitro.
AB  - Flavonoids, the active components of Epimedii Genus, have been demonstrated to
      protect against osteoporosis, cardiovascular diseases and rheumatoid arthritis.
      The present study aimed to investigate the neuroprotective effects of total
      flavonoid (TF) fraction of Epimedium koreanum Nakai on dopaminergic neurons in
      the cellular and mice models of Parkinson's disease (PD). TF pretreatment could
      ameliorate the decrease of striatal dopamine (DA) content and the loss of
      tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars
      compacta (SNpc) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      TF treatment could reverse the changes of Bcl-2 and Bax protein expressions in
      the striatum of PD mice. 1-Methyl-4-phenylpyridinium ion (MPP+) significantly
      decreased the cell viability and mitochondrial membrane potential in MES23.5
      cells. These effects could be reversed by TF treatment. In addition, MPP+-induced
      changes of Bcl-2 and Bax mRNA and protein expressions were also reversed by TF
      pretreatment. These data demonstrated that TF of E. koreanum Nakai could protect
      against MPTP-induced dopaminergic neuronal death in mice and MPP+-induced
      neurotoxicity in dopaminergic MES23.5 cells. Anti-apoptosis might be involved in
      this process.

PMID- 28494420
TI  - Egg shell waste as heterogeneous nanocatalyst for biodiesel production: Optimized
      by response surface methodology.
AB  - Worldwide consumption of hen eggs results in availability of large amount of
      discarded egg waste particularly egg shells. In the present study, the waste
      shells were utilized for the synthesis of highly active heterogeneous calcium
      oxide (CaO) nanocatalyst to transesterify dry biomass into methyl esters
      (biodiesel). The CaO nanocatalyst was synthesied by calcination-hydration
      dehydration technique and fully characterized by infrared spectroscopy, X-ray
      powder diffraction (XRD), scanning electron microscope (SEM), transmission
      electron microscope (TEM), brunauer-emmett-teller (BET) elemental and
      thermogravimetric analysis. TEM image showed that the nano catalyst had spherical
      shape with average particle size of 75 nm. BET analysis indicated that the
      catalyst specific surface area was 16.4 m2 g-1 with average pore diameter of 5.07
      nm. The effect of nano CaO catalyst was investigated by direct
      transesterification of dry biomass into biodiesel along with other reaction
      parameters such as catalyst ratio, reaction time and stirring rate. The impact of
      the transesterification reaction parameters and microalgal biodiesel yield were
      analyzed by response surface methodology based on a full factorial, central
      composite design. The significance of the predicted mode was verified and 86.41%
      microalgal biodiesel yield was reported at optimal parameter conditions 1.7%
      (w/w), catalyst ratio, 3.6 h reaction time and stirring rate of 140.6 rpm. The
      biodiesel conversion was determined by 1H nuclear magnetic resonance spectroscopy
      (NMR). The fuel properties of prepared biodiesel were found to be highly comply
      with the biodiesel standard ASTMD6751 and EN14214.

PMID- 28494421
TI  - Forest protected areas governance in Zimbabwe: Shift needed away from a long
      history of local community exclusion.
AB  - In this literature review based paper we explored the concept of exclusion of
      local communities from accessing resources in forest protected areas (FPAs) in
      Zimbabwe. We discussed the colonial and post-colonial forms, causes and
      mechanisms of exclusion and their social, economic and ecological outcomes. We
      examined the range of powers embodied in and exercised through various
      mechanisms, processes and social relations and their impact on local communities'
      access to FPA resources and associated benefits along the historical trajectory
      of forest governance in Zimbabwe. Results showed that the forms and extent of
      exclusion changed over time in tandem with the shifting political and economic
      landscape. During the colonial period, it was total exclusion whereby people were
      evicted from forest land as well as being denied access to basic resources for
      their livelihoods. Local communities' access to low value FPA resources improved
      during the post-colonial period but access to high value resources like
      commercial timber as well as sharing income benefits derived from FPA commercial
      activities remained a pipe dream. Regulation, legitimation, force and markets
      constituted the mixture of the power elements that FPA governing authorities used
      to exclude local communities. These powers remained intact despite attempts at
      collaborative governance in the 1990s. However, from the year 2000, local
      communities expressed their dissatisfaction with the centralised exclusionary
      governance system by invading the FPAs rendering them ungovernable. There is
      therefore a need for policy reform within the FPA sector to improve the current
      dire situation.

PMID- 28494422
TI  - Cyanobacteria blooms before and during the restoration process of a shallow urban
      lake.
AB  - Swarzedzkie Lake (near Poznan) has been heavily polluted. To improve the water
      quality, the restoration of lake by three methods: aeration, phosphorus
      inactivation using small doses of iron sulphate and magnesium chloride (FeSO4 and
      MgCl2) and biomanipulation was initiated at the end of 2011. The aim of the
      present study was to determine whether sustainable restoration has a significant
      impact on phytoplankton, especially cyanobacterial blooms in a shallow, urban,
      degraded lake. Therefore, phytoplankton and the physico-chemical parameters of
      water at the summer thermal stratification and autumn water mixing before (2011)
      and during restoration (2012-2014) was studied. Samples were collected at the
      deepest place of the lake in depth profile, every 1 m. Phytoplankton samples were
      preserved with Lugol's solution. The phytoplankton was counted using a Sedgewick
      Rafter chamber with a volume of 0.46 ml. Measurements of water temperature were
      made in the field with a YSI multiparameter meter, transparency - using a Secchi
      disk. Concentrations of nitrogen, phosphorus and chlorophyll a were analysed in
      the laboratory according to Polish standards. As a result of restoration the
      water quality of the lake has improved. Cyanobacteria had almost disappeared
      during the first year of restoration, however, a short bloom was observed
      (dominated by Pseudanabeana limnetica) in the second year. The main reason for
      this reappearance was a higher water temperature stimulating cyanobacteria
      growth, but an increased supply of phosphorus from the bottom sediments also
      contributed. A decrease in the temperature in the third year of restoration
      limited the growth of cyanobacteria again. Although the decrease in the
      phosphorus concentration as a result of restoration proved to be sufficient for
      average climatic conditions, it is highly likely to be more intense in the case
      of increased water temperature caused by global warming.

PMID- 28494423
TI  - Investigating sources of pharmaceutical pollution: Survey of over-the-counter and
      prescription medication purchasing, use, and disposal practices among university
      students.
AB  - Pharmaceutical pollution in surface waters poses a range of risks to public
      health and aquatic ecosystems. Consumers contribute to pharmaceutical pollution
      via use and disposal of medications, though data on such behaviors is limited.
      This paper investigates the purchasing, use, and disposal practices among a
      population that has been researched only minimally to date, yet will determine
      pharmaceutical pollution for decades to come: young adults represented by a
      university student population. We employed an online, 21-question survey to
      examine behaviors related to pharmaceuticals among students at the University of
      Vermont (n = 358). Results indicate that the majority of respondents had
      purchased medications in the previous 12 months (94%), and had leftover drugs
      (61%). Contrary to previous studies of older populations, only a small proportion
      of students had disposed of drugs (18%); municipal trash was the primary route of
      drug disposal (25%), and very few students disposed drugs via flushing (1%). Less
      than a quarter of students were aware of drug take-back programs (24%), and only
      4% had ever used take-back services. These findings indicate that the university
      student population may be storing a large volume of unused drugs that will
      require future disposal. Increasing awareness of, access to, and participation in
      pro-environment pharmaceutical behaviors, such as purchasing over-the-counter
      medication in smaller quantities and utilizing drug take-back programs, could
      minimize future pharmaceutical pollution from this population.

PMID- 28494424
TI  - Is environmental sustainability a strategic priority for logistics service
      providers?
AB  - Despite an increasing number of third-party logistics service providers (3PLs)
      regard environmental sustainability as a key area of management, there is still
      great uncertainty on how 3PLs implement environmental strategies and on how they
      translate green efforts into practice. Through a multiple case study analysis,
      this paper explores the environmental strategies of a sample of medium-sized 3PLs
      operating in Italy and the UK, in terms of environmental organizational culture,
      initiatives, and influencing factors. Our analysis shows that, notwithstanding
      environmental sustainability is generally recognised as a strategic priority, a
      certain degree of diversity in the deployment of environmental strategies still
      exists. This paper is original since the extant literature on green strategies of
      3PLs provides findings predominantly from a single country perspective and mainly
      investigates large/multinational organizations. It also provides indications to
      help managers of medium-sized 3PLs in positioning their business. This is
      particularly meaningful in the 3PL industry, where medium-sized organizations
      significantly contribute to the generated turnover and market value.

PMID- 28494425
TI  - Application of the WEAP model in strategic environmental assessment: Experiences
      from a case study in an arid/semi-arid area in China.
AB  - This article investigated how the use of a water resources assessment model
      contributed to one of the first strategic environmental assessments (SEA)
      conducted for arid/semi-arid regions in China. The study was based on the SEA of
      a coal industry development plan in Ordos, an arid/semi-arid region of northwest
      China, where a temporally and spatially simplified version of the WEAP (Water
      Evaluation And Planning System) model was applied for assessing the impact of the
      planned activities on local water resource system. Four scenarios were developed
      to simulate various alternatives using a diverse range of water utilisation
      measures such as irrigation efficiency, treatment and the reuse of water. The
      WEAP model itself was found to be a useful tool for efficient water resources
      assessment in SEA: 1) WEAP provides built-in simulation modules for water
      assessment, which improve the SEA's efficiency significantly; 2) WEAP temporally
      has the flexibility in both delivering information on a reasonably aggregated
      level by evaluating water resource on an annual time step, which fits most SEA
      cases, and being possible to take a finer time step analysis monthly, weekly even
      daily; 3) Spatially, WEAP has advantage in dealing with distributed demand sites
      in large spatial scale. However, although WEAP appears as a useful tool in
      providing support for decision-making, in this SEA case we experienced difficulty
      in building a feasible scenario to mitigate the impact of the proposed activities
      on the local water system, so that solution had to be found outside of the
      assessed scenarios - which led to the discussion on the fact that the proposed
      activities in SEA cases are rarely regarded as an uncertainty. Therefore future
      research on the scope of SEA scenarios could be valuable.

PMID- 28494426
TI  - The performance of the intensified constructed wetlands for organic matter and
      nitrogen removal: A review.
AB  - The effects of different aeration strategies including tidal flow (TF), effluent
      recirculation (ER) and artificial aeration (AA) on performance of vertical flow
      constructed wetland (VFCW), horizontal flow constructed wetland (HFCW) and hybrid
      constructed wetland (HCW) are comprehensively and critically reviewed in this
      paper. The removal efficiencies of nine types of intensified constructed wetlands
      (CWs) were examined in detail and their mean and standard deviation were
      estimated at 89 +/- 11%, 84 +/- 12%, 81 +/- 17% and 63 +/- 20% for total
      suspended solids (TSS), chemical oxygen demand (COD), ammonium-nitrogen (NH4+N)
      and total nitrogen (TN), respectively. From the studied CWs, ER-HCW, TF-HCW, AA
      VFCW and ER-VFCW emerged as the four best performing systems. The overall removal
      efficiency of TSS, COD, NH4+N and TN by ER-HCW was 98 +/- 2%, 85 +/- 11%, 83 +/-
      15% and 73 +/- 11%, respectively. Specifically, the ER enhances the interactions
      between pollutants and micro-organisms, consequently, the efficient removal of
      NH4+N and TN has been achieved in ER-HCW. The TF has a positive effect in
      refreshing the wetland with fresh air to enhance the dissolved oxygen (DO) in the
      system. In case of AA, intermittent aeration is more effective than continuous
      aeration, as it facilitates the establishment of aerobic and anaerobic conditions
      suitable for nitrification and denitrification. Statistical analysis shows that
      DO, organic loading rate and specific surface area requirement are the most
      significant factors that influence the performance of intensified CWs.

PMID- 28494427
TI  - On-line detection of Escherichia coli intrusion in a pilot-scale drinking water
      distribution system.
AB  - Improvements in microbial drinking water quality monitoring are needed for the
      better control of drinking water distribution systems and for public health
      protection. Conventional water quality monitoring programmes are not always able
      to detect a microbial contamination of drinking water. In the drinking water
      production chain, in addition to the vulnerability of source waters, the
      distribution networks are prone to contamination. In this study, a pilot-scale
      drinking-water distribution network with an on-line monitoring system was
      utilized for detecting bacterial intrusion. During the experimental Escherichia
      coli intrusions, the contaminant was measured by applying a set of on-line
      sensors for electric conductivity (EC), pH, temperature (T), turbidity, UV
      absorbance at 254 nm (UVAS SC) and with a device for particle counting. Monitored
      parameters were compared with the measured E. coli counts using the integral
      calculations of the detected peaks. EC measurement gave the strongest signal
      compared with the measured baseline during the E. coli intrusion. Integral
      calculations showed that the peaks in the EC, pH, T, turbidity and UVAS SC data
      were detected corresponding to the time predicted. However, the pH and
      temperature peaks detected were barely above the measured baseline and could
      easily be mixed with the background noise. The results indicate that on-line
      monitoring can be utilized for the rapid detection of microbial contaminants in
      the drinking water distribution system although the peak interpretation has to be
      performed carefully to avoid being mixed up with normal variations in the
      measurement data.

PMID- 28494429
TI  - Decompose the association between heatwave and mortality: Which type of heatwave
      is more detrimental?
AB  - BACKGROUND: Heatwaves is the most hazardous natural disaster in Australia and its
      health impacts need to be well unveiled, but how to properly define a heatwave is
      still debatable. This study aimed to identify which type of heatwave is more
      detrimental to health and to elucidate which temperature indicator is more
      suitable for heatwave definition and early warning. METHODS: We categorized
      temperature into extremely-hot and not-extremely-hot, and extremely-hot
      temperature refers to temperature at least >=96th percentile of the monthly
      temperature distribution, and accordingly, heatwaves were categorized into four
      types: 1) Type I: extremely-hot days followed by extremely-hot nights (HWboth);
      2) Type II: extremely-hot days followed by not-extremely-hot nights (HWday); 3)
      Type III: not-extremely-hot days followed by extremely-hot nights (HWnight); and
      4) Type IV: not-extremely-hot days followed by not-extremely-hot nights (HWwarm).
      A Poisson regression allowing for over-dispersion was used to examine the
      relationship between different types of heatwaves and mortality in Sydney,
      Melbourne and Brisbane using the data from 1988 to 2011. RESULTS: Mortality in
      Brisbane increased significantly during HWboth and HWwarm, and mortality in
      Melbourne increased significantly during HWboth and HWday. For Sydney, HWboth,
      HWwarm, and HWday were all associated with mortality increase, although no
      appreciable difference in the magnitudes of mortality increase among these three
      heatwave types was observed. HWnight was not associated with any significant
      mortality increase in these cities. Mean temperature is the best temperature
      indicator for heatwaves in Brisbane and maximum temperature is the best
      temperature indicator for heatwaves in Melbourne. CONCLUSIONS: Extremely-hot days
      rather than extremely-hot nights played a critical role in heatwave-related
      mortality. City-specific heatwave early warning may be optimal for Australia.

PMID- 28494428
TI  - Shotgun lipidomics in substantiating lipid peroxidation in redox biology: Methods
      and applications.
AB  - Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) has made
      profound advances for comprehensive analysis of cellular lipids. It represents
      one of the most powerful tools in analyzing lipids directly from lipid extracts
      of biological samples. It enables the analysis of nearly 50 lipid classes and
      thousands of individual lipid species with high accuracy/precision. The redox
      imbalance causes oxidative stress, resulting in lipid peroxidation, and
      alterations in lipid metabolism and homeostasis. Some lipid classes such as
      oxidized fatty acids, 4-hydroxyalkenal species, and plasmalogen are sensitive to
      oxidative stress or generated corresponding to redox imbalance. Therefore,
      accurate assessment of these lipid classes can provide not only the redox states,
      but also molecular insights into the pathogenesis of diseases. This review
      focuses on the advances of MDMS-SL in analysis of these lipid classes and
      molecular species, and summarizes their recent representative applications in
      biomedical/biological research. We believe that MDMS-SL can make great
      contributions to redox biology through substantiating the aberrant lipid
      metabolism, signaling, trafficking, and homeostasis under oxidative stress
      related condition.

PMID- 28494430
TI  - Novel cosmetic formulations containing a biosurfactant from Lactobacillus
      paracasei.
AB  - Cosmetic and personal care products including toothpaste, shampoo, creams,
      makeup, among others, are usually formulated with petroleum-based surfactants,
      although in the last years the consume trend for "green" products is inducing the
      replacement of surface-active agents in these formulations by natural
      surfactants, so-called biosurfactants. In addition to their surfactant capacity,
      many biosurfactants can act as good emulsifiers, which is an extra advantage in
      the preparation of green cosmetic products. In this work, a biosurfactant
      obtained from Lactobacillus paracasei was used as a stabilizing agent in oil-in
      water emulsions containing essential oils and natural antioxidant extract. In the
      presence of biosurfactant, maximum percentages of emulsion volumes (EV=100%) were
      observed, with droplets sizes about 199nm. These results were comparable with the
      ones obtained using sodium dodecyl sulfate (SDS), a synthetic well known
      surfactant with high emulsify capacity. Moreover, the biosurfactant and emulsions
      cytotoxicity was evaluated using a mouse fibroblast cell line. Solutions
      containing 5g/L of biosurfactant presented cell proliferation values of 97%,
      whereas 0.5g/L of SDS showed a strong inhibitory effect. Overall, the results
      herein gathered are very promising towards the development of new green cosmetic
      formulations.

PMID- 28494431
TI  - Silica nanoparticles as sources of silicic acid favoring wound healing in vitro.
AB  - There is good evidence that certain silicon-containing materials promote would
      healing and their common feature is the delivery of orthosilicic acid (Si(OH)4)
      either directly or following metabolism. In this respect, amorphous silica
      nanoparticles (NP), which dissolve in aqueous environments releasing up to 2mM
      orthosilicic acid, may be appropriate 'slow release' vehicles for bioactive
      silicon. Here we studied the impact of silica NP suspensions (primary
      particles~10nm) in undersaturated conditions (below 2mM Si) with differing
      degrees of surface charge and dissolution rate on human dermal fibroblasts (CCD
      25SK cells) viability, proliferation and migration in a cellular wound model.
      Silica was shown to be non-toxic for all forms and concentrations tested and
      whilst the anticipated stimulatory effect of orthosilicic acid was observed, the
      silica NPs also stimulated fibroblast proliferation and migration. In particular,
      the amine-functionalized particles promoted wound closure more rapidly than
      soluble orthosilicic acid alone. We suggest that this effect is related to easy
      cellular internalization of these particles followed by their intracellular
      dissolution releasing silicic acid at a faster rate than its direct uptake from
      the medium. Our findings indicate that amorphous silica-based NPs may favour the
      delivery and release of bioactive silicic acid to cells, promoting wound healing.

PMID- 28494432
TI  - Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels
      for ocular drug delivery.
AB  - Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via
      surfactant-free free-radical polymerization technique in aqueous conditions
      utilizing N,N'-methylene-bis-acrylamide (MBA) as a crosslinking agent. The
      PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to
      yield mucoadhesive materials which incorporate two mucoadhesive concepts;
      electrostatic interactions and covalent bond forming acrylate groups. The native
      PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo
      bovine conjunctival tissues, which was found to increase proportionally with the
      degree of quaternization. With a view to determine the ocular drug delivery
      capabilities of the materials, both quaternized and native nanogels were loaded
      with pilocarpine hydrochloride via an absorption method, and their in vitro
      release profiles were analysed. The nanogels were found to exhibit a high loading
      capacity (>20% of total weight) and a sustained release over 6h.

PMID- 28494433
TI  - Electrospun ultrathin PBAT/nHAp fibers influenced the in vitro and in vivo
      osteogenesis and improved the mechanical properties of neoformed bone.
AB  - Combining polyester scaffolds with synthetic nanohydroxyapatite (nHAp), which is
      bioactive and osteoconductive, is a plausible strategy to improve bone
      regeneration. Here, we propose the combination of PBAT [poly(butylene-adipate-co
      terephthalate)] and synthetic nHAp (at 3 and 5wt%). PBAT is a relatively a new
      polymer with low crystallinity and attractive biodegradability and mechanical
      properties for orthopedic applications, however, with a still underexplored
      potential for in vivo applications. Then, we performed a careful biological in
      vitro and in vivo set of experiments to evaluate the influence of PBAT containing
      two different nHAp loads. For in vitro assays, osteoblast-like MG63 cells were
      used and the bioactivity and gene expression related to osteogenesis were
      evaluated by qRT-PCR. For in vivo experiments, twenty-four male rats were used
      and a tibial defect model was applied to insert the scaffolds. Micro-computed
      tomography (Micro-CT) and histological analysis were used to assess e bone
      neoformation after 6 weeks of implantation. Three point flexural tests measured
      the mechanical properties of the neoformed bone. All scaffolds showed promising
      in vitro properties, since they were not cytotoxic against MG-63 cells and
      promoted high cell proliferation and formation of mineralized nodules. From a
      mechanistic point-of-view, nHAp loading increased hydrophilicity, which in turn
      allowed for a better adsorption of proteins and consequent changes in the
      phenotypic expression of osteoblasts. nHAp induced better cellular responses
      on/in the scaffolds, which was mainly attributed to its osteoconductive and
      osteoinductive properties. Micro-CT images showed that nHAp at 3% and 5wt% led to
      more effective bone formation, presenting the highest bone volume after 6 weeks
      of implantation. Considering the three point flexural tests, 5wt% of nHAp
      positively influenced the flexural mode of the neoformed bone, but the stiffiness
      was similar between the 3% and 5wt% groups. In summary, this investigation
      demonstrated great potential for the application of these novel scaffolds towards
      bone regeneration and, thus, should be further studied.

PMID- 28494434
TI  - P-Cadherin is necessary for retinal stem cell behavior in vitro, but not in vivo.
AB  - Adult retinal stem cells (RSCs) are rare quiescent cells within the ciliary
      epithelium of the eye, which is made up of non-pigmented N-Cadherin+ve inner and
      pigmented P-Cadherin+ve outer cell layers. Through FACs and single cell analyses,
      we have shown that RSCs arise from single cells from within the pigmented CE and
      express P-Cadherin. However, whether the expression of P-Cadherin is required for
      maintenance of the stem cell in vivo or in the formation of the clonal stem cell
      spheres in vitro is not known. Using cadherin functional blocking antibody
      experiments and a P-Cadherin -/- mouse to test whether the RSC population is
      affected by the loss of P-Cadherin expression, our experiments demonstrate that
      the RSCs reside in the pigmented CE layer and express P-Cadherin, which is
      important to the formation of adherent sphere colonies in vitro, however P
      Cadherin is not required for maintenance of RSCs in vivo.

PMID- 28494435
TI  - Impact of respiratory viruses in hospital-acquired pneumonia in the intensive
      care unit: A single-center retrospective study.
AB  - BACKGROUND: Data on the frequency and role of respiratory viruses (RVs) in
      hospital-acquired pneumonia (HAP) are still scarce. OBJECTIVES: We assessed the
      proportion of RVs and their impact on the outcome of hospital-acquired pneumonia
      (HAP) in the intensive care unit (ICU). STUDY DESIGN: Cases of HAP were
      retrospectively selected among patients who underwent screening for RVs by
      multiplex PCR (mPCR) in the ICU of a French tertiary care hospital from May 2014
      to April 2016. ICU length of stay and in-hospital mortality were compared between
      four groups defined according to the identified pathogens: virus only (V),
      virus/bacteria (V/B), bacteria only (B) and no pathogen (Neg). When available,
      previous mPCR was retrieved in order to assess possible chronic viral carriage.
      RESULTS: Overall, 95/999 (10%) ICU patients who underwent mPCR had HAP
      (V(17,18%), V/B(13,14%), B(60,63%), Neg(5,5%)). Median age was 61 years and 45
      (47%) were immunocompromised. Influenza (27%) and rhinovirus (27%) were the most
      common RVs. V/B group had higher mortality rate than B and V groups (62% vs. 40%
      and 35%, p=0.3) and a significantly longer length of stay (31days (18-48)) than V
      group (5days (3-11), p=0.0002)) and B group (14.5days (5.5-25.5), p=0.007)).
      Among the 15 patients with available mPCR tests before viral HAP, seven were
      negative and eight were positive corresponding to long-term carriage of community
      acquired viruses. DISCUSSION: RVs were detected in 32% of HAP patients who
      underwent mPCR. Two situations were encountered: (i) acute acquired viral
      infection; (ii) long-term viral carriage (mostly rhinovirus) especially in
      immunocompromised patients complicated by a virus/bacteria coinfection. The
      latter was associated with a longer length of stay and a trend toward a higher
      mortality.

PMID- 28494436
TI  - Neuronal tetraploidization in the cerebral cortex correlates with reduced
      cognition in mice and precedes and recapitulates Alzheimer's-associated
      neuropathology.
AB  - A controversy exists as to whether de novo-generated neuronal tetraploidy (dnNT)
      occurs in Alzheimer's disease. In addition, the presence of age-associated dnNT
      in the normal brain remains unexplored. Here we show that age-associated dnNT
      occurs in both superficial and deep layers of the cerebral cortex of adult mice,
      a process that is blocked in the absence of E2F1, a known regulator of cell cycle
      progression. This blockage correlates with improved cognition despite compromised
      neurogenesis in the adult hippocampus was confirmed in mice lacking the E2f1
      gene. We also show that the human cerebral cortex contains tetraploid neurons. In
      normal humans, age-associated dnNT specifically occurs in the entorhinal cortex
      whereas, in Alzheimer, dnNT also affects association cortices prior to
      neurofibrillary tangle formation. Alzheimer-associated dnNT is likely potentiated
      by altered amyloid precursor protein (APP) processing as it is enhanced in the
      cerebral cortex of young APPswe/PS1deltaE9 mice, long before the first amyloid
      plaques are visible in their brains. In contrast to age-associated dnNT, enhanced
      dnNT in APPswe/PS1deltaE9 mice mostly affects the superficial cortical layers.
      The correlation of dnNT with reduced cognition in mice and its spatiotemporal
      course, preceding and recapitulating Alzheimer-associated neuropathology, makes
      this process a potential target for intervention in Alzheimer's disease.

PMID- 28494437
TI  - Nanosecond pulsed electric field induced changes in cell surface charge density.
AB  - This study reports that the surface charge density changes in Jurkat cells with
      the application of single 60 nanosecond pulse electric fields, using atomic force
      microscopy. Using an atomic force microscope tip and Jurkat cells on silica in a
      0.01M KCl ionic concentration, we were able to measure the interfacial forces,
      while also predicting surface charge densities of both Jurkat cell and silica
      surfaces. The most important finding is that the pulsing conditions varyingly
      reduced the cells' surface charge density. This offers a novel way in which to
      examine cellular effects of pulsed electric fields that may lead to the
      identification of unique mechanical responses. Compared to a single low field
      strength NsPEF (15kV/cm) application, exposure of Jurkat cells to a single high
      field strength NsPEF (60kV/cm) resulted in a further reduction in charge density
      and major morphological changes. The structural, physical, and chemical
      properties of biological cells immensely influence their electrostatic force; we
      were able to investigate this through the use of atomic force microscopy by
      measuring the surface forces between the AFM's tip and the Jurkat cells under
      different pulsing conditions as well as the interfacial forces in ionic
      concentrations.

PMID- 28494438
TI  - Assessment of Intra- and Inter-Rater Reliability of Three Methods for Measuring
      Atopic Dermatitis Severity: EASI, Objective SCORAD, and IGA.
AB  - BACKGROUND: Numerous different scoring systems have been proposed for assessing
      the severity of atopic dermatitis (AD). Many of these methods did not undergo
      proper validation and reliability testing. OBJECTIVE: The aim of our study was to
      compare the reliability and reproducibility of the Eczema Area and Severity Index
      (EASI), objective Scoring Atopic Dermatitis (oSCORAD), and Investigator Global
      Assessment (IGA). METHODS: On the scoring day, 10 trained dermatologists
      evaluated 10 adult patients with AD using the EASI, oSCORAD, and IGA. All
      subjects were assessed twice by each physician. Correlations between measures
      were analysed using the Pearson correlation coefficient. The intra-class
      correlation coefficient (ICC) was calculated to assess intra-rater reliability;
      the coefficient of variation (CV) was used to assess inter-rater variability.
      RESULTS: Significant positive correlations were observed between each scale in
      both assessments. The ICCs for the EASI and oSCORAD were 0.71 and 0.66,
      respectively, indicating good reliability, while the ICC for the IGA (0.54)
      indicated only fair reliability. The CVs for the oSCORAD and IGA were 28.1 and
      33.0, respectively, indicating moderate variability. The CV for the EASI was
      66.5, indicating high variability. CONCLUSION: Among the 3 compared scales, the
      oSCORAD had the highest inter-rater reliability, whereas the EASI had the highest
      intra-rater reliability. None of the 3 scoring methods showed a significant
      advantage over the other. Thus, a reliable assessment of AD severity requires the
      use of at least 2 independent measurements simultaneously.

PMID- 28494439
TI  - Centromere Repositioning in Cattle (Bos taurus) Chromosome 17.
AB  - Eukaryotic organisms have developed a structure, called centromere, able to
      preserve the integrity of the genome during cell division. A young bull from the
      Marchigiana breed, with a normal external phenotype, underwent routine
      cytogenetic analysis to enter the reproduction center. All metaphases analyzed
      showed an unusual biarmed chromosome of medium size despite a diploid set of
      chromosomes (2n = 60,XY). FISH analysis excluded a pericentric inversion or a
      reciprocal translocation, but highlighted a repositioning of the centromere in
      BTA17. The satellite DNA was still in an acrocentric position. The telomeres were
      normally present. The primary constriction on the abnormal chromosome was C-band
      negative. Finally, the absence of a large genomic deletion in the BTA17
      pericentromeric region was demonstrated by both array-CGH analysis and SNP array.
      To our knowledge, this is the first case of centromere repositioning reported in
      cattle.

PMID- 28494440
TI  - Nuclear Architecture of Mouse Spermatocytes: Chromosome Topology,
      Heterochromatin, and Nucleolus.
AB  - The nuclear organization of spermatocytes in meiotic prophase I is primarily
      determined by the synaptic organization of the bivalents that are bound by their
      telomeres to the nuclear envelope and described as arc-shaped trajectories
      through the 3D nuclear space. However, over this basic meiotic organization, a
      spermatocyte nuclear architecture arises that is based on higher-ordered patterns
      of spatial associations among chromosomal domains from different bivalents that
      are conditioned by the individual characteristics of chromosomes and the
      opportunity for interactions between their domains. Consequently, the nuclear
      architecture is species-specific and prone to modification by chromosomal
      rearrangements. This model is valid for the localization of any chromosomal
      domain in the meiotic prophase nucleus. However, constitutive heterochromatin
      plays a leading role in shaping nuclear territories. Thus, the nuclear
      localization of nucleoli depends on the position of NORs in nucleolar bivalents,
      but the association among nucleolar chromosomes mainly depends on the presence of
      constitutive heterochromatin that does not affect the expression of the ribosomal
      genes. Constitutive heterochromatin and nucleoli form complex nuclear territories
      whose distribution in the nuclear space is nonrandom, supporting the hypothesis
      regarding the existence of a species-specific nuclear architecture in first
      meiotic prophase spermatocytes.

PMID- 28494441
TI  - Different Successful Management Strategies for Obstructing Renal Parapelvic
      Cysts.
AB  - Parapelvic cysts originate in the renal parenchyma and extend into the renal
      sinus. A series of 3 patients with symptomatic obstructing parapelvic cysts is
      described, 2 with acute presentations, and 1 with chronic symptoms. In 2 of the 3
      cases, there was a significant delay in establishing a diagnosis. Although one
      individual was successfully managed by image-guided cyst aspiration, the second
      patient required repeated aspiration due to cyst re-accumulation. A high index of
      clinical suspicion and a combination of imaging modalities, including serial
      ultrasound, excretory-phase CT, and MAG3 renogram, are necessary to establish the
      diagnosis and monitor response to treatment.

PMID- 28494442
TI  - Efficacy of Hyaluronic Acid/Carboxymethyl Cellulose-Based Bioresorbable Membranes
      in Reducing Perihepatic Adhesion Formation: A Prospective Cohort Study.
AB  - BACKGROUND: Perihepatic adhesions induced by hepatectomy make the subsequent
      repeat hepatectomy technically demanding. The aim of this study was to verify the
      effect of hyaluronic acid/carboxymethyl cellulose-based bioresorbable membrane
      (HA membrane) in preventing posthepatectomy adhesion formation by focusing on the
      ease of the adhesiolysis in subsequent hepatectomy for recurrent tumors. METHODS:
      A total of 201 patients who underwent hepatectomy using HA membrane were
      prospectively followed-up for 3 years. Thirty of the 201 patients underwent a
      repeat hepatectomy for recurrence. The operative data of 85 cases of repeat
      hepatectomy, the primary hepatectomy of which had been performed without the use
      of HA membrane, served as the historical control data. The primary endpoint was
      the time interval between the skin incision and the start of hepatic parenchymal
      transection (the preparation time) including adhesiolysis. Secondary endpoints
      were blood loss during the operation, incidence of postoperative complications,
      and the biochemical data. RESULTS: The median preparation time (183 vs. 228 min;
      p = 0.027) and total operation time (374 vs. 439 min; p = 0.041) were
      significantly shorter in the HA membrane group than in the control group.
      CONCLUSION: Use of HA membranes during hepatectomy enabled significant shortening
      of the adhesiolysis time during the sequential hepatectomy performed for
      recurrent tumors.

PMID- 28494443
TI  - Short-Term Clinical and Oncological Outcomes after Single-Incision Plus One Port
      Laparoscopic Anterior Resection for Rectal Cancer.
AB  - AIM: In the past, we developed and reported single-incision plus one port
      laparoscopic anterior resection (SILS + 1-AR) of the rectum. In this study, we
      reviewed our experiences with 141 consecutive patients admitted in a community
      hospital for undergoing SILS + 1-AR for rectal cancer and evaluated the short
      term clinical and oncological outcomes. METHODS: A lap protector (LP) was
      inserted through a 2.5 cm transumbilical incision; an EZ-access was mounted to
      the LP and three 5-mm ports were placed. A 12-mm port was inserted in the right
      lower quadrant. RESULTS: One hundred thirty-six patients (96.5%) completed their
      treatment with SILA+1-AR. The number of tumor locations in the rectosigmoid,
      rectum area above the peritoneal reflection (Ra), and rectum area below the
      peritoneal reflection (Rb) were 44, 63, and 29 respectively. Six (5.6%) tumor
      recurrences or metastasis occurred in 107 patients with stages I-III disease with
      a median follow-up of 30 months. One patient with a positive surgical margin
      rejected additional resection of the positive margin and died of recurrent
      disease. CONCLUSION: Our initial experiences suggested that SILS + 1-AR is a
      feasible and a safe treatment option for rectal cancer patients treated by
      experienced surgeons specialized in SILS. However, further studies are needed to
      demonstrate the advantages of this procedure compared to the benefits of
      conventional laparoscopic AR.

PMID- 28494444
TI  - Associations of Usual 24-Hour Sodium and Potassium Intakes with Blood Pressure
      and Risk of Hypertension among Adults in China's Shandong and Jiangsu Provinces.
AB  - BACKGROUND/AIMS: High sodium intake and low intake of potassium can increase
      blood pressure (BP) and risk of developing hypertension. Few studies have
      examined the association between 24-h urinary sodium and potassium excretion and
      BP or risk of hypertension in China, and most used only a single 24-h urinary
      sample. METHODS: We analyzed data on 2281 participants aged 18-69 years by using
      two 24-h urinary sodium and potassium excretions from the supplemental baseline
      survey of the Shandong-Ministry of Health Action on Salt Reduction and
      Hypertension (SMASH) project. We used measurement error models to estimate usual
      intakes, multivariable linear regression to assess their association with B P,
      and logistic regression to estimate the risk of hypertension. RESULTS: The
      average usual intakes of sodium and potassium, and the mean sodium-potassium
      ratio, were 166.9 mmol/day, 25.3 mmol/day, and 6.8, respectively. All three
      measures were significantly associated with systolic BP (SBP) and diastolic BP
      (DBP), with an increase of 1.39 mmHg (95% confidence interval [CI] 0.44?2.34) in
      SBP and 0.94 mmHg (95% CI 0.34?1.55) in DBP for a 1-standard deviation (SD)
      (25.6mmol/day) increase in sodium intake, a decrease of 1.42 mmHg (95% CI -2.37? 
      0.47) in SBP and 0.91 mmHg (95% CI -1.52? -0.30) in DBP for a 1-SD (3.4 mmol/day)
      increase in potassium intake, and an increase of 0.97 mmHg (95% CI 0.36?1.58) in
      SBP and of 0.65 mmHg (95% CI 0.26?1.04) in DBP per unit increase in the sodium-to
      potassium ratio. The adjusted odds ratios comparing the risk of hypertension
      among adults in the highest with those in the lowest quintile differ
      significantly for potassium (0.51; 95% CI 0.29?0.88) and sodium-to-potassium
      ratio (1.40; 95% CI 1.01?1.94). CONCLUSIONS: Our results suggested that higher
      sodium and lower potassium intakes are associated with increased BP and risk of
      hypertension in the Shandong and Jiangsu adults.

PMID- 28494445
TI  - Mechanisms of Improved Exercise Performance under Hyperoxia: On Haldane, Geppert,
      Zunz, and Eschenbacher Transformations.

PMID- 28494446
TI  - Mutation Load of Multiple Ion Channel Gene Mutations in Brugada Syndrome.
AB  - Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all
      sudden cardiac death cases in individuals with a structurally normal heart.
      Pathogenic variants associated with Brugada syndrome have been identified in over
      19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In
      contrast to other arrhythmogenic channelopathies (such as long QT syndrome),
      digenic inheritance has never been reported in Brugada syndrome. Exploring 66
      cardiac genes using a new custom next-generation sequencing panel, we identified
      a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada
      syndrome patient. The parents were heterozygous for each variation. This novel
      finding highlights the role of mutation load in Brugada syndrome and strongly
      suggests the adoption of a gene panel to obtain an accurate genetic diagnosis,
      which is mandatory for risk stratification, prevention, and therapy.

PMID- 28494447
TI  - Stromal Growth Differentiation Factor 15 and Its Association with Ovarian Cancer.
AB  - BACKGROUND/AIMS: Growth differentiation factor 15 (GDF-15) is induced by pro
      inflammatory cytokines. Higher levels of GDF-15 have been associated with
      malignancy. The aim of the study was to evaluate both tissue and serum levels of
      GDF-15 in ovarian neoplasms. METHODS: A cohort study evaluated 31 patients with
      benign ovarian tumors and 34 patients with ovarian cancer were evaluated in 2
      years. The inclusion criterion was histopathological diagnosis of ovarian
      epithelial neoplasia. Exclusion criteria were secondary malignant ovarian
      neoplasia and preoperative treatment. Serum and tissue levels of GDF-15 were
      assessed by enzyme-linked immunosorbent assay and immunohistochemistry,
      respectively. Chi-square test and unpaired t test were performed. RESULTS: Serum
      levels were higher in the patients with malignant neoplasms than in the patients
      with benign tumors, yet the difference was not statistically significant. GDF-15
      immunostaining was significantly more frequent in the stroma of the malignant
      tumors than in the stroma of the benign tumors (p = 0.0034). CONCLUSION: GDF-15
      staining is elevated in the stroma of ovarian cancer, demonstrating that it may
      be a potential diagnostic and therapeutic target.

PMID- 28494448
TI  - Effects of CYP2C19 Variants on Fluoxetine Metabolism in vitro.
AB  - AIMS: CYP2C19 is an important member of the cytochrome P450 enzyme superfamily.
      We recently identified 31 CYP2C19 alleles in the Han Chinese population. The aim
      of this study was to assess the catalytic activities of these allelic isoforms
      and their effects on the metabolism of fluoxetine in vitro. METHODS: The wild
      type and 30 CYP2C19 variants were expressed in insect cells and each variant was
      characterized using fluoxetine as the substrate. Reactions were performed at 37
      degrees C with 20-1,000 umol/L substrate for 30 min. By using ultra-high
      performance liquid chromatography-mass spectrometry to detect the products, the
      kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of norfluoxetine
      were determined. RESULTS: Among the CYP2C19 variants tested, T130M showed similar
      intrinsic clearance (Vmax/Km) values with CYP2C19*1, while the intrinsic
      clearance values of other variants were significantly decreased (from 9.56 to
      77.77%). In addition, CYP2C19*3 and *35FS could not be detected because they have
      no detectable enzyme activity. CONCLUSION: In China, the assessment of CYP2C19
      variants in vitro offers valuable information relevant to the personalized
      medicine for CYP2C19-metabolized drug.

PMID- 28494449
TI  - Effect of the Serum Inhibited Gene (Si1) on Autophagy and Apoptosis in MCF-7
      Breast Cancer Cells.
AB  - BACKGROUND/AIMS: The serum inhibited gene (Si1) was named according to its
      inhibited expression in response to serum exposure. Si1 has an important
      relationship with tumors. Autophagy and apoptosis are two types of cell death.
      However, there are few studies regarding the association between Si1 and
      autophagy, or apoptosis in tumors. In this, we investigated the effect of Si1 on
      the proliferation and cell cycle progression of MCF-7 cells and its influence on
      autophagy and apoptosis in MCF-7 cells. METHODS: To investigate these functions
      of Si1 in tumor cells, we firstly constructed a pEGFP-Si1 overexpression vector
      and a pSilencer-Si1 interference vector, and we subsequently tested the
      proliferation and cell cycle progression of MCF-7 cells using the MTT assay and
      flow cytometry, and we then detected autophagy by western blotting and MDC
      (Monodansylcadaverine) staining as well as apoptosis by western blotting and
      Hoechst 33258 staining. RESULTS: We found that the Si1 gene can significantly
      inhibit the viability of MCF-7 cells and arrest the cell cycle at the G2/M phase.
      Si1 can induce autophagy through upregulation of LC3-II and Beclin1, it can
      induce apoptosis through cleavage of PARP in MCF-7 cells. CONCLUSION: Altogether,
      our study indicated that Si1 can inhibit cell proliferation of MCF-7, and also
      induces autophagy and apoptosis. This study firstly investigated the effect of
      Si1 on autophagy and apoptosis in MCF-7 cells. Moreover, it also improves the
      current understanding of the mechanisms related to the effect of Si1 on tumor
      cells and also provides a foundation for gene-targeted therapy.

PMID- 28494450
TI  - Stachydrine Protects Against Pressure Overload-Induced Cardiac Hypertrophy by
      Suppressing Autophagy.
AB  - BACKGROUND: Autophagy is required for the maintenance of cardiomyocyte
      homeostasis. However, excessive autophagy plays a maladaptive role in pressure
      overload-induced heart failure. To identify mechanisms by which Stachydrine
      inhibits pressure overload-induced cardiac hypertrophy, we determined inhibitory
      activities against activation of NADPH oxidase, reactive oxygen species(ROS)
      production and excessive activation of autophagy. METHODS: Stachydrine was
      administered intragastrically to Wistar rats after Transverse aortic
      constriction(TAC) and H9c2 cells were treated with Stachydrine after Angiotension
      II stimulation. The activation of NADPH oxidase2 required the membrane
      translocation of p47phox and p67phox. Cell membrane fraction was isolated by
      ultracentrifuge in sucrose. The expression of p67phox, p47phox, gp91phox subunit
      in the cell membrane were determined by western blot. The combination of p67phox
      and gp91 phox subunit was detected by immunofluorescence staining. The expression
      of phosphorylated p47phox subunit was determined by western blot. The
      intracellular ROS were measured with DCF-DA fluoresence. The autophagic flux was
      measured by recording the fluorescence emission of the fusion protein mRFP-GFP
      LC3 by dynamic live-cell imaging. Reuslts: We report here that stachydrine, a
      major constituent of Leonurus heterophyllus Sweet, inhibited AngII-induced
      excessive autophagy within H9c2 cells. Stachydrine blocked the over
      phosphorylation of the p47phox subunit, decreased the translocation of p47phox
      and p67phox to the membrane, inhibited the activity of NOX2, and reduced the
      generation of ROS. We also demonstrated that stachydrine ameliorated TAC-induced
      cardiac hypertrophy, dysfunction and excessive autophagy in vivo. CONCLUSIONS:
      Our study highlights the importance of regulating NOX2 when autophagy is
      obviously activated. By inhibiting NOX2, Stachydrine inhibits ROS production,
      thus exerting a remarkable activity of inhibiting hypertrophy, which could have
      considerable effect on clinical practice.

PMID- 28494451
TI  - Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model.
AB  - BACKGROUND: Colorectal cancer is the main leading cause of cancer-related deaths
      worldwide. Present data suggest that plant-derived anthocyanins have anti
      inflammatory and chemopreventive properties. This study was aimed at evaluating
      the effect of an anthocyanin-rich extract from bilberries on colorectal tumour
      development and growth in the administration of azoxymethan (AOM)/dextran sodium
      sulfate (DSS) mouse model. METHODS: Colonic carcinogenesis was induced by AOM and
      DSS 3 or 5%, respectively, in 50 female Balb/c mice. Mice received either normal
      food (controls) or a diet containing either 10 or 1% anthocyanin-rich bilberry
      extract. Colonoscopy took place at week 4 and 9 after initiation of
      carcinogenesis. After termination at week 9, colon samples were analysed
      macroscopically and microscopically. RESULTS: Mice receiving 10% anthocyanins
      showed significantly (p < 0.004) less reduced colon length (12.1 cm [8.5-14.4
      cm]) as compared to controls (11.2 cm [9.8-12.3]) indicating less inflammation.
      Mice fed with 10% anthocyanin-rich extract revealed significantly less mean
      tumour numbers (n = 1.2) compared to control (n = 14) and anthocyanin 1% treated
      mice (n = 10.6, p < 0.001). CONCLUSION: Anthocyanins prevented the formation and
      growth of colorectal cancer in AOM/DSS-treated Balb/c mice. Further studies
      should investigate the mechanisms of how anthocyanins influence the development
      of colorectal cancer.

PMID- 28494452
TI  - The Novel Ser18del AVP Variant Causes Inherited Neurohypophyseal Diabetes
      Insipidus by Mechanisms Shared with Other Signal Peptide Variants.
AB  - BACKGROUND/AIM: Variability in the severity and age at onset of autosomal
      dominant familial neurohypophyseal diabetes insipidus (adFNDI) may be associated
      with certain types of variants in the arginine vasopressin (AVP) gene. In this
      study, we aimed to describe a large family with an apparent predominant female
      occurrence of polyuria and polydipsia and to determine the underlying cause.
      METHODS: The family members reported their family demography and symptoms. Two
      subjects were diagnosed by fluid deprivation and dDAVP challenge tests. Eight
      subjects were tested genetically. The identified variant along with 3 previously
      identified variants in the AVP gene were investigated by heterologous expression
      in a human neuronal cell line (SH-SY5Y). RESULTS: Both subjects investigated
      clinically had a partial neurohypophyseal diabetes insipidus phenotype. A
      g.276_278delTCC variant in the AVP gene causing a Ser18del deletion in the signal
      peptide (SP) of the AVP preprohormone was perfectly co-segregating with the
      disease. When expressed in SH-SY5Y cells, the Ser18del variant along with 3 other
      SP variants (g.227G>A, Ser17Phe, and Ala19Thr) resulted in reduced AVP mRNA,
      impaired AVP secretion, and partial AVP prohormone degradation and retention in
      the endoplasmic reticulum. Impaired SP cleavage was demonstrated directly in
      cells expressing the Ser18del, g.227G>A, and Ala19Thr variants, using state-of
      the-art mass spectrometry. CONCLUSION: Variants affecting the SP of the AVP
      preprohormone cause adFNDI with variable phenotypes by a mechanism that may
      involve impaired SP cleavage combined with effects at the mRNA, protein, and
      cellular level.

PMID- 28494453
TI  - The Peptidoglycan Recognition Proteins PGRPLA and PGRPLB Regulate Anopheles
      Immunity to Bacteria and Affect Infection by Plasmodium.
AB  - Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators
      that is conserved from insects to mammals. In the malaria vector mosquito
      Anophelescoluzzii, the peptidoglycan receptor PGRPLC activates the immune
      deficiency (Imd) pathway limiting both the microbiota load and Plasmodium
      infection. Here, we carried out an RNA interference screen to examine the role of
      all 7 Anopheles PGRPs in infections with Plasmodium berghei and P. falciparum. We
      show that, in addition to PGRPLC, PGRPLA and PGRPS2/PGRPS3 also participate in
      antiparasitic defenses, and that PGRPLB promotes mosquito permissiveness to P.
      falciparum. We also demonstrate that following a mosquito blood feeding, which
      promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and
      negatively regulate the activation of the Imd pathway, respectively. Our data
      demonstrate that PGRPs are important regulators of the mosquito epithelial
      immunity and vector competence.

PMID- 28494454
TI  - Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent
      System.
AB  - Previously, we have shown that extracellular basic pH plays a significant role in
      both the direct and indirect regulation of cellular processes in a wound; this in
      turn affects the wound-healing process. Several studies have demonstrated the
      importance of apoptosis modulation in the wound-healing process, especially in
      removing inflammatory cells and in inhibiting scar formation. However, the
      effects of extracellular basic pH on wound healing-related skin damage are yet to
      be examined. Therefore, we investigated the induction of accelerated apoptosis by
      extracellular basic pH in skin. Apoptosis-related protein levels were measured
      using an array kit, target protein expression levels were detected by
      immunostaining, lactate dehydrogenase was analyzed spectrophotometrically, and
      Annexin V levels were measured by fluorescence staining. Basic pH (8.40) strongly
      upregulated extrinsic apoptosis proteins (Fas, high temperature requirement A,
      and p21) and slightly upregulated intrinsic apoptosis proteins (cytochrome c, B
      cell lymphoma 2 [Bcl-2], Bcl-2-associated death promoter, and Bcl-2-like protein
      4) in a 3D human skin equivalent system. Moreover, basic pH (8.40) induced heat
      shock protein (HSP) 60 and 70. In addition, basic pH-exposed Fas- and HSP60
      knockdown cells showed significantly decreased levels of apoptosis. Taken
      together, these results indicate that extracellular basic pH increases early
      stage apoptosis through Fas/FasL via modulation of HSP60 and HSP70.

PMID- 28494455
TI  - The Clinical Impact of Bet v 6 in Birch Pollen-Sensitized Patients.
AB  - BACKGROUND: Bet v 6, a minor birch pollen allergen, is commercially available for
      allergen-specific IgE antibody testing. However, there is hardly any literature
      on the clinical impact of Bet v 6. The aim of the present study was to analyze if
      testing specific IgE against Bet v 6 can add valuable benefit to the standard
      diagnostics of birch pollen-sensitized patients, especially in patients with
      unknown sensitization-eliciting allergens. METHODS: Birch pollen-sensitized
      patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for
      specific IgE antibodies against Bet v 6. For comparison, an equal number of
      randomly selected patients with birch pollen sensitization, regardless of their
      individual sensitization patterns, were tested for specific anti-Bet v 6.
      RESULTS: Of 57 cases with missing reactivity against the standard birch pollen
      allergens, 2 patients were positive for Bet v 6. In the representative sample, 3
      patients showed specific IgE against Bet v 6 - resulting in a total prevalence of
      5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure
      to birch pollen or an oral allergy syndrome. An increased prevalence of asthma
      and a higher degree of sensitization were the only distinctive clinical features
      in Bet v 6-positive patients. CONCLUSIONS: Among birch pollen-sensitized
      patients, the prevalence of specific IgE against Bet v 6 is low. Further,
      sensitization to Bet v 6, which shows characteristics of a panallergen, remains
      clinically silent. Therefore, determination of anti-Bet v 6 is not considered
      useful in the clinical routine.

PMID- 28494456
TI  - Proton Magnetic Resonance Spectroscopy Study on the Metabolism Changes of
      Cerebellum in Patients with Post-Stroke Depression.
AB  - OBJECTIVE: To study the metabolic changes of cerebellum by proton magnetic
      resonance Spectroscopy (1H-MRS) and discuss the relationships between the
      cerebellar changes and depression severity in patients with post-stroke
      depression. METHODS AND RESULTS: Data of demographic characteristics, individual
      history and life style of all subjects were collected. 40 patients with stroke
      and 20 controls were enrolled. All groups received T1WI, T2WI, DWI and 1H-MRS
      examination. The cerebral infarction volume and the distribution and severity of
      leukoaraiosis were evaluated. The ratios of NAA/Cr, Cho/Cr and Cho/NAA in the
      cerebellum were calculated. There were no statistical significant difference in
      the NAA/Cr, Cho/Cr and Cho/NAA ratios in bilateral cerebellum between CONT group
      and NORM group. The Cho/Cr and Cho/NAA ratios in the cerebellum contralateral to
      the stroke region were higher in PSD group than those in NORM and CONT groups,
      and the Cho/Cr and Cho/NAA ratios in the cerebellum ipsilateral to the stroke
      region were similar with those in NORM and CONT groups. However, there were no
      statistical significant difference in the NAA/Cr ratios in bilateral cerebellum
      among three groups. CONCLUSION: The result shows preliminarily that the
      cerebellum involves in the development of post-stroke depression.

PMID- 28494457
TI  - Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via
      Activation of Silent Information Regulator 1.
AB  - BACKGROUND/OBJECTIVES: The polyphenol resveratrol (Rev) has been found to exhibit
      various beneficial effects including prevention of pulmonary arterial
      hypertension (PAH). The present study was designed to investigate the action and
      potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent
      Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells
      (PASMCs). METHODS: PAH rats were established by exposure to hypoxia for 21 days.
      Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by
      gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then
      treated with Rev or SRT1720 in vitro. Western blot was performed to detect the
      protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out
      to verify cell proliferation. In addition, the TUNEL positive assay and flow
      cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability
      transition (mPT) was identified by confocal microscopy. Right ventricular
      systolic pressure (RVSP) was determined with a Gould pressure transducer, and
      right ventricular hypertrophy (RVH) was determined by weighing the cardiac
      muscle. RESULTS: We demonstrated that Rev could reverse the remodelling of the
      pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down
      regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious
      effect on the protein expression of SIRT1. In addition, Rev could induce
      mitochondrial swelling and nuclear pyknosis, leading to small, dense, and
      dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited
      PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720,
      a specific activator of SIRT1, significantly retarded PASMC proliferation and
      promoted PASMC apoptosis in vitro. The mechanism could be associated with
      inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and
      reduced RVH. CONCLUSION: Rev produced a beneficial effect partially by enhancing
      the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation
      increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel
      future strategy for the treatment of PAH.

PMID- 28494458
TI  - Improvement of Anal Function by Adipose-Derived Stem Cell Sheets.
AB  - AIM: One of the most troublesome complications of anal preserving surgery is anal
      sphincter dysfunction. The aim of this study was to evaluate functional recovery
      after implantation of adipose-derived stem cell (ADSC) sheets, novel
      biotechnology, for an anal sphincter resection animal model. METHODS: Eighteen
      female Sprague-Dawley rats underwent removal of the nearest half of the internal
      and external anal sphincter muscle. Nine rats received transplantation with ADSC
      sheets to the resected area while the remaining rats received no transplantation.
      The rats were evaluated for the anal function by measuring their resting pressure
      before surgery and on postoperative days 1, 7, 14, 28, and 56. In addition, the
      rats were examined for the presence of smooth muscle and also to determine its
      origin. RESULTS: The improvement of the anal pressure was significantly greater
      in the ADSC sheet transplantation group compared with the control group.
      Histologically, at the vicinity of the remaining smooth muscle, reproduction of
      smooth muscle was detected. Using in fluorescence in situ hybridization, the
      cells were shown to be from the recipient. CONCLUSION: Regenerative therapy using
      ADSC sheet has the potential to recover anal sphincter dysfunction due to
      anorectal surgery.

PMID- 28494459
TI  - Influence of Bovine Serum Lipids and Fetal Bovine Serum on the Expression of Cell
      Surface Markers in Cultured Bovine Preadipocytes.
AB  - To establish the influence of fetal bovine serum (FBS) and bovine serum lipids
      (BSL) on cell differentiation marker expression, bovine adipose-derived stem
      cells from subcutaneous tissue were incubated for 14 days in 4 types of
      differentiation media containing 10% FBS and 10 uL/mL BSL (TRT-1), no FBS and 10
      uL/mL of BSL (TRT-2), 10% FBS and no BSL (TRT-3), or no supplements (TRT-4).
      Cells were subjected to Nile red staining, immunocytochemistry (CD73, CD90,
      CD105, DLK1, FabP4), and quantitative real-time PCR (CD73, CD90, CD105, FabP4).
      The number of cells presenting FabP4 and the percentage of mature adipocytes with
      large lipid droplets were increased in TRT-2, accompanied by a robust increase in
      FabP4 mRNA abundance and a decrease in DLK1-positive cells. In preadipocytes,
      CD73 was present around the nucleus and translocated towards cell membranes
      during differentiation. Although the percentage of CD73-positive cells was not
      different among treatments, its mRNA abundance, immunocytochemical staining
      intensity, and translocation towards cell membranes were decreased when the
      medium contained no FBS (TRT-2 and TRT-4). All cells showed a diffuse
      distribution of CD90 and CD105 and remained positive for these markers
      irrespective of the treatment. However, the CD90 and CD105 mRNA abundance was
      decreased in TRT-2 and TRT-4; i.e., in media containing no FBS. The presence of
      FBS increased the absolute number of cell nuclei as assessed by DAPI
      fluorescence. Our results suggest that bovine subcutaneous preadipocytes display
      typical stem cell markers. The differentiation into mature adipocytes is promoted
      by BSL, whereas FBS endorses cell proliferation.

PMID- 28494460
TI  - Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain
      Injury.
AB  - Excitotoxicity plays a key role during insults to the developing brain such as
      neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults
      affect many thousands of infants each year. Excitotoxicity causes frank lesions
      due to cell death and gliosis and disturbs normal developmental process, leading
      to deficits in learning, memory, and social integration that persist into
      adulthood. Understanding the underlying processes of the acute effects of
      excitotoxicity and its persistence during brain maturation provides an
      opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and
      designing possible therapies. We applied mass spectrometry to provide metabolic
      profiles of brain tissue and plasma over time following an excitotoxic lesion
      (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found
      no differences between the plasma from the control (PBS-injected) and excitotoxic
      (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In
      the brain, we found that variations in amino acids (arginine, glutamine,
      phenylananine, and proline) and glycerophospholipids were sustaining acute and
      delayed (tertiary) responses to injury. In particular, the effect of the
      excitotoxic lesion on the normal profile of development was linked to alterations
      in a fingerprint of glycerophospolipids and amino acids. Specifically, we
      identified increases in the amino acids glutamine, proline, serine, threonine,
      tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the
      glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine
      (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic
      profiling is a useful approach to identify acute and tertiary effects in an
      excitotoxic lesion model, and generating a short list of targets with future
      potential in the hunt for identification, stratification, and possibly therapy.

PMID- 28494461
TI  - Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound
      Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for
      Improvement.
AB  - INTRODUCTION: Since the WHO Classification of Tumours of the Digestive System has
      been published in 2010, resected pancreatic neuroendocrine tumours (pNETs) are
      graded as grade 1 (G1), grade 2 (G2) or grade 3 (G3) using the Ki67 labelling
      index (Ki67-LI). Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is
      often used for diagnosis, but few studies have assessed its value for grading.
      AIMS: The aims of this study were to compare the Ki67-LI obtained by cytological
      grading (cG) with that obtained by histological grading (hG) and to assess (1)
      the influence of tumour size and the number of counted cells on FNA grading as
      well as (2) the overall survival (OS) and progression-free survival based on cG.
      MATERIALS AND METHODS: EUS-FNA was performed for 102 pNETs (57 resected). cG (200
      cells counted) was done on all FNAs. For 29 FNAs, >2,000 cells were counted (14
      resected). A comparison was made between hG and cG for the 57 resected patients.
      Patients were followed up until June 2016. RESULTS: cG was consistent with hG in
      39 of 57 patients with a concordance rate of 72% using a Ki67-LI cut-off of 5%
      for G1/G2. For Ki67-LI absolute values, the correlation was r = 0.443 and
      increased to r = 0.824 (p < 0.001) when only FNAs with >2,000 cells were counted.
      Twenty-one of 22 pNETs <2 cm had the same grading on cG and hG, whereas grading
      was discordant for 15 of 16 pNETs >2 cm. Thirty-eight patients died after 70.5
      months of follow-up. OS for the whole cohort was 235 months and differed between
      cG1 (235 months), cG2 (36.3 months) and cG3 (10.9 months). CONCLUSION: cG of
      pNETs is more accurate when tumours measure <2 cm and more cells are counted on
      FNA. Discrepancies are seen between G2 tumours which are often considered G1 on
      FNA due to tumour heterogeneity. EUS-FNA is valuable to distinguish between
      patients with good (cG1) and poor (cG3) prognosis.

PMID- 28494462
TI  - In vitro Growth Pattern of Primary Human Osteoblasts on Calcium Phosphate- and
      Polymethylmethacrylate-Based Bone Cement.
AB  - BACKGROUND/PURPOSE: Polymethylmethacrylate (PMMA) and calcium phosphate (Ca-P)
      cements are widely used for arthroplasty surgery and augmentation of bone
      defects. However, aseptic implant loosening in absence of wear-induced osteolysis
      indicates an unfavourable interaction between the cement surface and human
      osteoblasts. Our underlying hypothesis is that cement surfaces directly modify
      cell viability, proliferation rate, and cell differentiation. METHODS: To test
      this hypothesis, we examined primary human osteoblasts harvested from six
      individuals. These cells were pooled and subsequently seeded directly on cement
      pellets prepared from Palacos(r) R, Palacos(r) R+G, and Norian(r) Drillable
      cements. After incubation for 24 and 72 h, cell viability, proliferation rate,
      apoptosis rate, and cell differentiation were analysed. RESULTS: Upon cultivation
      of human osteoblasts on cement surfaces, we observed a significantly reduced cell
      viability and DNA content compared to the control. Analysis of the apoptosis rate
      revealed an increase for cells on Palacos R and Norian Drillable, but a
      significant decrease on Palacos R+G compared to the control. Regarding osteogenic
      differentiation, significantly lower values of alkaline phosphatase enzyme
      activity were identified for all cement surfaces after 24 and 72 h compared to
      cultivation on tissue culture plastic, serving as control. CONCLUSIONS: In
      summary, these data suggest a limited biocompatibility of both PMMA and Ca-P
      cements, necessitating further research to reduce unfavourable cell-cement
      interactions and consequently extend implant survival.

PMID- 28494463
TI  - Plasma Drug Concentrations in Patients with Pulmonary Arterial Hypertension on
      Combination Treatment.
AB  - BACKGROUND: Combination therapy with the phosphodiesterase type 5 inhibitors (PDE
      5i) sildenafil or tadalafil and the endothelin receptor antagonists (ERA)
      bosentan, ambrisentan, or macitentan may cause mutual pharmacokinetic
      interactions in patients with pulmonary arterial hypertension (PAH). OBJECTIVE:
      The objective of this study was to analyze plasma drug concentrations in PAH
      patients receiving different combination treatments. METHODS: PAH patients
      receiving a stable combination treatment with ERA and PDE-5i with targeted dosage
      for at least 1 month were routinely assessed, including clinical parameters and
      plasma drug concentrations. Concentrations were normalized considering dose and
      time from last medication intake and presented as multiples of the expected mean
      (MoM) of the respective monotherapies. RESULTS: A total of 125 PAH patients (84
      female, 41 male, 57% idiopathic/heritable) were included. Sildenafil and
      tadalafil concentrations were lowest in combination with bosentan (MoM 0.44 +/-
      0.42, 95% confidence interval [CI] 0.30-0.57, and MoM 0.89 +/- 0.53, 95% CI 0.50
      1.28, respectively) compared to the combination with ambrisentan (MoM 1.3 +/-
      0.97, 95% CI 0.86-1.73, and MoM 1.67 +/- 0.63, 95% CI 1.40-1.94, respectively)
      and macitentan (MoM 1.16 +/- 0.87, 95% CI 0.86-1.46, and MoM 1.59 +/- 0.99, 95%
      CI 0.80-2.38, respectively). The combination of sildenafil and bosentan led to
      more than twice the expected bosentan concentrations in 53.8%. Patients switching
      from sildenafil-bosentan to macitentan showed a significant increase in
      sildenafil concentrations (p < 0.001). CONCLUSIONS: Only the combination with
      macitentan or ambrisentan led to targeted mean PDE-5i plasma concentrations and
      should therefore be preferred to combination with bosentan. Sildenafil-bosentan
      showed the strongest interaction, with low sildenafil and high bosentan
      concentrations. The study was not powered to analyze whether lower PDE-5i
      concentrations cause unsatisfying clinical response. However, plasma
      concentrations within a targeted range are desirable and may become of increasing
      importance.

PMID- 28494464
TI  - Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus
      Calmette-Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling
      Pathway.
AB  - BACKGROUND/AIMS: The purpose of this study is to explore the immunoregulatory
      role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in
      macrophages in response to Bacillus Calmette-Guerin (BCG) infection. METHODS:
      After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG,
      miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG,
      inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway),
      and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were
      used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL
      6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell
      viability was measured using an MTT assay. Cell apoptosis and necrosis rates were
      detected using flow cytometry. RESULTS: Compared with the control group, miR-21
      expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and
      necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as
      cell viability, were reduced in BCG infection groups. Compared with the BCG
      group, miR-21 expression was increased in the miR-21 mimic + BCG group but
      decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG
      groups. The expression of TLR4 and MyD88, as well as the cell viability, were
      decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and
      necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups.
      The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with
      the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher
      expression of TLR4 and MyD88 as well as higher cell viability and lower levels of
      TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21
      inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with
      the miR-21 inhibitor + BCG group. CONCLUSION: Our results suggest that miR-21 can
      negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell
      viability, increased cell apoptosis and increased levels of inflammatory factors
      following BCG infection in macrophages.

PMID- 28494465
TI  - Congenital Salivary Gland Anlage Tumor: An Unusual Anterior Skull Base Mass in
      the Neonatal Period.
AB  - Congenital salivary gland anlage tumor (SGAT) is a benign nasopharyngeal mass
      that presents with respiratory distress in infancy. Prior case reports have
      characterized SGAT as a lesion of the nasopharynx without intracranial extension.
      We report a unique case of SGAT extending through the anterior skull base and
      discuss the differential diagnosis and management of this unusual entity.

PMID- 28494466
TI  - Let-7a Inhibits T-Cell Proliferation and IFN-gamma Secretion by Down-Regulating
      STAT3 Expression in Patients with Psoriasis.
AB  - OBJECTIVE: This study aimed to explore the effects of STAT3 targeting by let-7a
      on T-cell proliferation and IFN-gamma secretion in psoriasis. METHODS: From
      January 2013 to January 2015, 40 patients with psoriasis (psoriasis group) and 38
      volunteers undergoing plastic surgery (control group) were enrolled in this
      study. Pearson correlation analysis was performed to evaluate the correlation
      between let-7a and STAT3 expression. T-cells were isolated and subjected to
      different transfection methods. A dual luciferase reporter assay was carried out
      to confirm STAT3 as a target gene of let-7a. Let-7a, STAT3 and IFN-gamma mRNA
      expression was detected by quantitative real-time fluorescent polymerase chain
      reaction (qRT-PCR), and pSTAT3 protein levels were determined by Western blot. T
      cell proliferation was evaluated with a cell counting kit-8 (CCK-8) assay.
      RESULTS: The level of STAT3 mRNA and pSTAT3 was higher, but let-7a expression was
      lower in the psoriasis group than the control group. Pearson correlation analysis
      indicated that STAT3 expression was negatively correlated with let-7a expression.
      T-cells transfected with inhibitors exhibited greater IFN-gamma mRNA expression
      and T-cell proliferation than transfected T-cells and T-cells transfected with a
      non-sense sequence, while T-cells transfected with let-7a mimics exhibited lower
      IFN-gamma mRNA expression and T-cell proliferation than transfected T-cells and T
      cells transfected with a non-sense sequence. This suggested that siRNA-STAT3
      could reverse the increase in IFN-y mRNA expression and T-cell proliferation
      induced by let-7a inhibitors. CONCLUSION: Our results demonstrated that let-7a
      inhibits T-cell proliferation and IFN-gamma secretion by down-regulating STAT3 in
      psoriasis.

PMID- 28494467
TI  - Expression and Characterization of Functional Recombinant Bet v 1.0101 in the
      Chloroplast of Chlamydomonas reinhardtii.
AB  - BACKGROUND: Allergen immunotherapy (AIT) still plays a minor role in the
      treatment of allergic diseases. To improve the acceptance of AIT by allergic
      patients, the treatment has to become more convenient and efficacious. One
      possibility is the oral application of allergens or derivatives thereof.
      Therefore, we sought to produce a recombinant allergen in the green alga
      Chlamydomonas reinhardtii as a novel production platform. METHODS: The major
      birch pollen allergen Bet v 1 was selected as candidate molecule, and a codon
      optimized gene was synthesized and stably integrated into the microalga C.
      reinhardtii FUD50. Positive transformants were identified by PCR, cultured, and
      thereafter cells were disrupted by sonication. Bet v 1 was purified from algal
      total soluble protein (TSP) by affinity chromatography and characterized
      physicochemically as well as immunologically. RESULTS: All transformants showed
      expression of the allergen with yields between 0.01 and 0.04% of TSP. Algal
      derived Bet v 1 displayed similar secondary structure elements as the Escherichia
      coli-produced reference allergen. Moreover, Bet v 1 produced in C. reinhardtii
      showed binding comparable to human IgE as well as murine Bet v 1-specific IgG.
      CONCLUSION: We could successfully produce recombinant Bet v 1 in C. reinhardtii.
      As microalgae are classified as GRAS (generally recognized as safe), the pilot
      study supports the development of novel allergy treatment concepts such as the
      oral administration of allergen-containing algal extracts for therapy.

PMID- 28494468
TI  - Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder:
      CACNA1C, CHRNA1, and MAPK1.
AB  - BACKGROUND: Bipolar disorder (BPD) is a common and severe mental disorder. The
      involvement of genetic factors in the pathophysiology of BPD is well known. In
      the present study, we tested the association of several single-nucleotide
      polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1)
      with BPD. These genes are involved in monoamine-related pathways, as well as in
      dendrite development, neuronal survival, synaptic plasticity, and
      memory/learning. METHODS: One hundred and thirty-two subjects diagnosed with BPD
      and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within
      CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes
      within each gene were compared in cases and controls. Interactions between
      variants in different loci were also tested. RESULTS: Significant differences in
      the distribution of alleles between the cases and controls were detected for
      rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and
      rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also
      confirmed an involvement of variations within these genes in BPD. Finally,
      exploratory epistatic analyses demonstrated potential interactive effects,
      especially regarding variations in CACNA1C and CHRNA7. LIMITATIONS: Limited
      sample size and risk of false-positive findings. DISCUSSION: Our data suggest a
      possible role of these 3 genes in BPD. Alterations of 1 or more common brain
      pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may
      explain the obtained results.

PMID- 28494470
TI  - Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using
      electronic primary care records.
AB  - BACKGROUND: Pre-existing non-cancer conditions may complicate and delay
      colorectal cancer diagnosis. METHOD: Incident cases (aged ?40 years, 2007-2009)
      with colorectal cancer were identified in the Clinical Practice Research
      Datalink, UK. Diagnostic interval was defined as time from first symptomatic
      presentation of colorectal cancer to diagnosis. Comorbid conditions were
      classified as 'competing demands' (unrelated to colorectal cancer) or
      'alternative explanations' (sharing symptoms with colorectal cancer). The
      association between diagnostic interval (log-transformed) and age, gender,
      consultation rate and number of comorbid conditions was investigated using linear
      regressions, reported using geometric means. RESULTS: Out of the 4512 patients
      included, 72.9% had ?1 competing demand and 31.3% had ?1 alternative explanation.
      In the regression model, the numbers of both types of comorbid conditions were
      independently associated with longer diagnostic interval: a single competing
      demand delayed diagnosis by 10 days, and four or more by 32 days; and a single
      alternative explanation by 9 days. For individual conditions, the longest delay
      was observed for inflammatory bowel disease (26 days; 95% CI 14-39). CONCLUSIONS:
      The burden and nature of comorbidity is associated with delayed diagnosis in
      colorectal cancer, particularly in patients aged ?80 years. Effective clinical
      strategies are needed for shortening diagnostic interval in patients with
      comorbidity.

PMID- 28494469
TI  - Mutation status among patients with sinonasal mucosal melanoma and its impact on
      survival.
AB  - BACKGROUND: Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas and
      lacks well-characterised molecular markers. Our aim was to determine the
      frequencies of common mutations and examine their utility as molecular markers in
      a large series of primary SNMMs. METHODS: SNMM patients seen at our institution
      from August 1991 through July 2016 were identified. Genomic DNA was extracted
      from 66 formalin-fixed paraffin-embedded tumours and screened for mutations by
      direct sequencing. We investigated the association of mutations with
      clinicopathological features and survival outcomes. RESULTS: Overall, 41% (27 out
      of 66) of the SNMMs harboured mutations. BRAF and KIT mutations were identified
      in 8% (five patients) and 5% (three patients) of SNMMs, respectively, whereas
      NRAS mutations were detected in 30% (20 patients) of SNMMs. Mutation rates in
      these oncogenes were similar between SNMMs located in the paranasal sinuses and
      those in the nasal cavity (30% and 13%, respectively, P=0.09). In a multivariate
      analysis, patients with negative margins had significantly better overall
      survival (hazard ratio 5.43, 95% confidence interval 1.44-21.85, P=0.01) and
      disease-specific survival (hazard ratio 21.9, 95% confidence interval 3.71-180,
      P=0.0004). The mutation status of the tumours showed no association with survival
      outcomes. CONCLUSIONS: In SNNM, mutation status does not affect survival
      outcomes, but NRAS mutations are relatively frequent and could be targeted in
      this disease by MEK inhibitors.

PMID- 28494472
TI  - A tale of two islands-trauma care in New Zealand.

PMID- 28494473
TI  - Improving outcomes in orthopaedic care.

PMID- 28494471
TI  - Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a
      3p/Bcl-w axis in glioblastoma.
AB  - : Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in
      the central nervous system. Previously, we found that neurotensin (NTS) and its
      high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and
      invasiveness of glioblastoma. Unexpectedly, cell death also appeared by
      inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were
      remained to be further explored. METHODS: Cells treated with SR48692, a selective
      antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the
      apoptosis was assessed by flow cytometry. Cytochrome c release was detected by
      using immunofluorescence. Mitochondrial membrane potential (MMP, DeltaPsim) loss
      was stained by JC-1 and detected by immunofluorescence or flow cytometry.
      Apoptosis antibody array and microRNA microarray were performed to seek the
      potential regulators of NTSR1 inhibition-induced apoptosis. Interaction between
      let-7a-3p and Bcl-w 3'UTR was evaluated by using luciferase assay. RESULTS:
      SR48692 induced massive apoptosis, which was related to mitochondrial cytochrome
      c release and MMP loss. Knockdown of NTSR1 induced slight apoptosis and
      significant MMP loss. In addition, NTSR1 inhibition sensitised glioblastoma cells
      to actinomycin D or doxorubicin-induced apoptosis. Consistently, NTSR1 inhibition
      induced mitochondrial apoptosis was accompanied by downregulation of Bcl-w and
      Bcl-2. Restoration of Bcl-w partly rescued NTSR1 deficiency-induced apoptosis. In
      addition, NTSR1 deficiency promoted higher let-7a-3p expression and inhibition
      let-7a-3p partly rescued NTSR1 inhibition-induced apoptosis. In addition, let-7a
      3p inhibition promoted 3'UTR activities of Bcl-w and the expression of c-Myc and
      LIN28, which were the upstream of let-7a-3p, decreased after NTSR1 inhibition.
      CONCLUSIONS: NTSR1 had an important role in protecting glioblastoma from
      intrinsic apoptosis via c-Myc/LIN28/let-7a-3p/Bcl-w axis.

PMID- 28494474
TI  - The 'six hour target' in New Zealand is associated with reduced mortality and
      greater efficiency.

PMID- 28494475
TI  - Impact of a national time target for ED length of stay on patient outcomes.
AB  - AIM: The impact of national targets for emergency department (ED) length of stay
      (LOS) on patient care is unclear. This study aimed to determine the effect of New
      Zealand's six-hour time target (95% of ED patients discharged or admitted to
      hospital within six hours) on a range of quality indicators. METHODS: A
      nationwide observational study from 2006 to 2012 modelled differences in changes
      over time before and after target introduction in 2009. The observed model
      estimates in 2012 were compared to those predicted if pre-target trends had
      continued. Differences are absolute values except for morality, which is
      presented as a relative change. RESULTS: There were 5,793,767 ED presentations
      and 2,082,374 elective admissions from 18 out of a possible 20 district health
      boards included in the study. There were clinically important reductions in
      hospital LOS (-0.29 days), EDLOS (-1.1 hours), admitted patients EDLOS (-2.9
      hours), ED crowding (-26.8%), ED mortality (-57.8%), elective inpatient mortality
      (-42.2%) and the proportion not waiting for assessment (-2.8%). Small changes
      were seen in time to assessment in the ED (-3.4 minutes), re-presentation to ED
      within 48 hours of the index ED discharge (-0.7%), re-presentation to ED within
      48 hours from ward discharge (+0.4%) and acute admissions (+3.9%). An increase
      was observed in re-admission to a ward within 30 days of discharge (1.0%). These
      changes were all statistically significant (p<0.001). CONCLUSION: Most outcomes
      we investigated either improved or were unchanged after the introduction of the
      time target policy in New Zealand. However, attention is required to ensure that
      reductions in hospital length of stay are not at the expense of subsequent re
      admissions.

PMID- 28494476
TI  - Effect of the Shorter Stays in Emergency Departments time target policy on key
      indicators of quality of care.
AB  - AIM: To determine whether implementation of a national health target called
      Shorter Stays in Emergency Departments impacted on clinical markers of quality of
      care. METHOD: A retrospective pre- and post-intervention study from 2006 to 2012
      examined quality of care metrics for five different indicators at different sites
      in relation to the implementation of the target using a general linear model for
      times to treatment. Explanatory variables included period (pre- or post-target),
      ethnicity, age, deprivation and severity of condition. Back transformed least
      square means were used to describe the outcomes. RESULTS: The times to treatment
      for ST elevation myocardial infarction; 36.9 (28-49) vs 47.6 (36-63) minutes
      p=0.14, antibiotics for severe sepsis; 105.9 (73-153) vs 104.3 (70-155) minutes
      p=0.93, analgesia for moderate or severe pain; 48 (31-75) vs 46 (32-66) minutes p
      =0.77, theatre for fractured neck of femur; 35.4 (32.1-39.1) vs 32.4 (29.2-36.1)
      hours, and to theatre for appendicitis; 14.1 (12-17) vs 16.4 (14-20) hours were
      unchanged after implementation of the target. Treatment adequacy was also
      unchanged for these indicators. CONCLUSION: Introduction of the Shorter Stays in
      Emergency Departments target was not associated with any clinically important or
      statistically significant changes in the time to treatment and adequacy of care
      for five different clinical indicators of quality of care in Aotearoa New
      Zealand. For those indicators measured at one site only, it is unknown whether
      these results can be generalised to other sites.

PMID- 28494477
TI  - New Zealand plastic surgeons' life-time contribution to peer-reviewed literature.
AB  - AIM: The New Zealand Medical Association commits the New Zealand doctor to
      evidence-based medicine, scholarship, teaching, collaboration and communication.
      To assess this commitment, one measure, contribution to the peer-reviewed
      literature, was examined for one group of New Zealand doctors: plastic surgeons.
      METHOD: Plastic surgeons with a current practising certificate were identified on
      the New Zealand medical register (April 2016). Scopus database was searched for
      publications by each. RESULTS: Sixty-five surgeons authored 541 unique items in
      134 journals, generating 8,047 citations. Between medical graduation and
      specialty qualification, a mean 1.8 items were published per practitioner (range
      0-11). Twenty-three practitioners (35.4%) did not publish during this time.
      Between specialty qualification and the end of 2015, mean number of items
      published per surgeon was 7.3 (range 0-97). Thirteen (20.0%) surgeons had not
      published since specialist qualification. The general trend was for surgeons to
      become less productive with increasing time in practice. Mean surgeon h-index was
      4.4 (range 0-26). Four surgeons (6.2%) had not published at any time. CONCLUSION:
      As a group, but with exceptions and less so in later practice, New Zealand
      plastic surgeons would seem to demonstrate commitment to evidence-based medicine,
      scholarship, teaching, collaboration and communication expected of a New Zealand
      doctor, as evidenced by peer-review publication.

PMID- 28494478
TI  - Survival of Legionella in earthquake-induced soil disturbance (liquefaction) in
      residential areas, Christchurch, New Zealand: implications for disease.
AB  - AIM: To investigate a possible link between liquefaction dust exposure and the
      noticeable increase in legionellosis cases in response to major earthquakes in
      2010 and 2011 that resulted in widespread soil disturbance (liquefaction) in
      parts of Christchurch, New Zealand. METHOD: We culture tested liquefaction
      affected soil for Legionella spp. in the six months following the first
      earthquake in 2010. Thirty silt samples were collected randomly from locations
      within Christchurch's metropolitan area that were affected by liquefaction. The
      samples were tested to determine the presence of Legionella using qualitative and
      quantitative methods. Liquefaction-affected soil samples from three sites were
      further subjected to particle size distribution analysis and determination of
      major oxides. A controlled field study was established using six silt samples and
      one control (commercial compost), seeded with a wild-type strain of Legionella
      bozemanae serogroup (sg) 1 and persistence monitored over a 60-day period by
      culturing for the presence of Legionella. Dry matter determinations were
      undertaken so that total Legionella could be calculated on a dry weight basis.
      RESULTS: Legionella bacteria were undetectable after day one in the silt samples.
      However, L. bozemanae sg1 was detected in the control sample for the entire study
      period. CONCLUSION: This study showed that the liquefaction-affected soil could
      not contribute directly to the observed increase in legionellosis cases after the
      earthquakes due to its inability to support growth and survival of the Legionella
      bacteria.

PMID- 28494479
TI  - A walking stick in one hand and a chainsaw in the other: patients' perspectives
      of living with multimorbidity.
AB  - AIMS: Multimorbidity is common, yet there are major gaps in research,
      particularly among younger and indigenous populations. This research aimed to
      understand patients' perspectives of living with multimorbidity. METHODS: A
      qualitative study of 61 people living with multimorbidity, 27 of whom were Maori
      and a third aged under 65, from urban and rural regions in New Zealand. Six focus
      groups and 14 interviews were conducted, recorded, transcribed and analysed.
      RESULTS: For many participants, living with multimorbidity disrupted their
      'normal' lives, posing challenges in everyday activities such as eating and
      toileting, working and managing medications. Dealing with the health system posed
      challenges such as accessing appointments and having enough time in
      consultations. Cultural competency, good communication and continuity of care
      from healthcare providers were all valued. Participants had many recommendations
      to improve management, including a professional single point of contact to
      coordinate all specialist care. CONCLUSIONS: Living with multimorbidity is often
      challenging requiring people to manage their conditions while continuing to live
      their lives. This research suggests changes are needed in the health system in
      New Zealand and elsewhere to better manage multimorbidity thus improving
      patient's lives and reducing costs to the health sector and wider society.

PMID- 28494480
TI  - Implementation and effects of Enhanced Recovery After Surgery for hip and knee
      replacements and fractured neck of femur in New Zealand orthopaedic services.
AB  - AIM: The National Orthopaedic Enhanced Recovery After Surgery (ERAS)
      Collaborative was launched in November 2013 to implement ERAS protocols for hip
      and knee total joint arthroplasty (TJA) and fractured neck of femur (NOF) in
      participating district health boards (DHBs) by December 2014. This paper reports
      on the results. METHOD: ERAS protocols were developed for hip and knee TJA and
      fractured NOF. Breakthrough Series collaborative methodology was used to
      implement the ERAS protocols in 18 DHBs. We collected monthly data on compliance
      with protocols and average length of stay (ALOS). Data were analysed using run
      charts and Shewhart control charts. RESULTS: The national percentage of ERAS
      components achieved across all DHBs rose from 33% to 75% on the elective knee TJA
      pathway, from 31% to 78% on the elective hip TJA pathway and from 29% to 51% on
      the acute fractured NOF pathway. The ALOS for knee TJA reduced from 5.4 days to
      4.5 days. The ALOS for hip TJA reduced from 5.1 days to 4.3 days. There was no
      change in the ALOS for fractured NOF. CONCLUSION: The National Orthopaedic ERAS
      Collaborative increased uptake of ERAS protocols across all three pathways and
      decreased ALOS for the elective pathways among participating DHBs. There was no
      decrease in ALOS for the fractured NOF pathway. Collaborative improvement
      methodology can be used successfully to implement orthopaedic ERAS across New
      Zealand DHBs.

PMID- 28494481
TI  - Enhanced hip fracture management: use of statistical methods and dataset to
      evaluate a fractured neck of femur fast track pathway-pilot study.
AB  - The increasing elderly population and subsequent rise in total hip fracture(s) in
      this group means more effective management strategies are necessary to improve
      efficiency. We have changed our patient care strategy from the emergency
      department (ED), acute orthopaedic wards, operating theatre, post-operation and
      rehabilitation, and called it Fracture Neck of Femur Fast Track Pathway. All
      clinical data and actions were captured, integrated and displayed on a weekly
      basis using 'signalfromnoise' (SFN) software. The initial four months analysis of
      this project showed significant improvement in patient flow within the hospitals.
      The overall length of stay was reduced by four days. Time in ED was reduced by 30
      minutes, and the wait for rehabilitation reduced by three days. Overall time in
      rehabilitation reduced by 3-7 days depending on facility. On average, fast track
      patients spent 95 less hours in hospital, resulting in 631 bed days saved in this
      period, with projected savings of NZD700,000. No adverse effects were seen in
      mortality, readmission and functional improvement status. Fractured neck of femur
      has increasing clinical demand in a busy tertiary hospital. Length of stay, co
      morbidities and waiting time for theatres are seen as major barriers to treatment
      for these conditions. Wait for rehabilitation can significantly lengthen hospital
      stay; also poor communication between the individual hospital management facets
      of this condition has been an ongoing issue. Lack of instant and available
      electronic information on this patient group has also been seen as a major
      barrier to improvement. This paper demonstrates how integration of service
      components that are involved in fractured neck of femur can be achieved. It also
      shows how the use of electronic data capture and analysis can give a very quick
      and easily interpretable data trend that will enable change in practice. This
      paper indicates that cooperation between health professionals and practitioners
      can significantly improve the length of stay and the time in which patients can
      be returned home. Full interdisciplinary involvement was the key to this
      approach. The use of electronic data capture and analysis can be used in many
      other health pathways within the health system.

PMID- 28494482
TI  - Increased use of police and health-related services among those with heavy
      drinkers in their lives in New Zealand.
AB  - AIMS: To report population estimates of service use because of someone else's
      drinking in New Zealand, investigate whether greater exposure to heavy drinkers
      relates to greater service use and examine demographic predictors of such service
      use. METHODS: A general population survey of respondents aged 12-80 years was
      conducted in New Zealand. The sample size was 3,068 and response rate 64%.
      Respondents' use of police and health-related services because of someone else's
      drinking were measured along with self-reports of heavy drinkers in their lives,
      demographic variables and own drinking. RESULTS: Ten percent of New Zealanders
      reported having called the police at least once in the past 12 months because of
      someone else's drinking-corresponding to 378,843 New Zealanders making at least
      one call to police. Almost 7% of the sample, representing 257,613 New Zealanders,
      reported requiring health-related services at least once for the same reason.
      CONCLUSIONS: There are considerable numbers of New Zealanders requiring
      intervention from police or health-related services due to the effects of someone
      else's drinking. Further, increased exposure to heavy drinkers among respondents
      predicted increased service use. Heavy drinkers place increased burden on police
      and health-related services, not only because of directly attributable effects
      but because they impact others.

PMID- 28494483
TI  - The cost of major head and neck cancer surgery.
AB  - AIM: This study quantified the cost of major head and neck cancer (HNC) surgery.
      METHODS: Consecutive patients undergoing major HNC surgery between July 2007 and
      June 2012 were identified from our head and neck database. Patient demographics,
      tumour type, site, stage and types of resection and reconstruction, length of
      stay and surgical complications occurring within six months of initial surgery
      were retrospectively analysed. The actual cost of initial surgical treatment and
      hospital income were calculated. RESULTS: Two hundred and forty-five patients
      underwent major HNC surgery, most commonly for mucosal squamous cell carcinoma
      (SCC) and metastatic and/or locally advanced cutaneous SCC. Neck dissection and
      parotidectomy were the commonest resection procedures and free flaps the
      commonest reconstructive procedures performed. Forty-two patients developed
      surgical complications within six months of the initial major HNC surgery. Over
      the five-year period, surgery cost a total of NZ$5,130,639.00, averaging
      NZ$20,941.38 per patient, not including costs such as incidentals, while the
      hospital received NZ$4,976,559.61 averaging NZ$20,229.91/patient. On average,
      oral cavity cancer, metastatic and/or locally advanced skin cancer, and skull
      base cancer cost NZ$22,694.72/patient, NZ$17,373.64/patient and
      NZ$47,295.95/patient, respectively. CONCLUSION: Calculated hospital income
      marginally covered the actual cost of major HNC surgery, which places substantial
      financial burden on the hospital. The anatomic site of the tumour determines the
      cost of treatment.

PMID- 28494484
TI  - Is high-quality trauma care "business as usual" in New Zealand?
AB  - New Zealand is on the cusp of establishing a world-class trauma system. Many of
      the building blocks are in place with national and regional guidelines in both
      the pre-hospital and hospital phases of care established. A dedicated clinical
      workforce is available in all DHBs and national data available through the Major
      Trauma Registry. The greatest threat to achieving high-quality trauma care in New
      Zealand at this point is governance stability rather than clinical variability.
      Now is the time to lock the trauma system into a framework not subject to
      political or bureaucratic whims.

PMID- 28494485
TI  - Rotorua, hydrogen sulphide and Parkinson's disease-A possible beneficial link?
AB  - AIM: Rotorua city (New Zealand) is known for its 'rotten egg' smell, due to high
      levels of hydrogen sulphide (H2S) concentrations emitted from local geothermal
      vents. Studies have shown H2S as potentially toxic if too high in concentration.
      However, some health benefits have been observed at lower concentrations. This
      article summarises what is known about effects of H2S on health and postulates
      whether ambient air inhalation levels of H2S in Rotorua might have a therapeutic
      role in the management of motor symptoms in Parkinson's disease (PD). RESULTS:
      Chronic H2S inhalation has been shown to have a protective factor on dopaminergic
      neurons of animal models of PD. A large-scale survey of long-term Rotorua
      residents showed no evidence of health detriment nor impairment of cognitive
      functions. Intriguingly, however, participants in higher H2S exposures showed a
      tendency for faster motor response times in a finger tapping test. One of the PD
      Motor Rating Scale examination tests for PD is finger tapping speed, as this is
      associated with motor performance. Might it be that relatively high, but safe,
      H2S levels in Rotorua could help protect the degradation of dopaminergic neurons
      associated with PD? CONCLUSION: An observed beneficial link between chronic H2S
      inhalation in PD animal models and improved finger tapping scores in a sample of
      the Rotorua population, linked to dopaminergic nerve function, is worth
      investigating further.

PMID- 28494486
TI  - Acute calcific tendinitis of the longus colli muscle.

PMID- 28494487
TI  - A case of confirmed primary hyperaldosteronism diagnosed despite normal screening
      investigations.
AB  - Primary hyperaldosteronism is a common cause of hypertension in the adult
      population. We report a case of histologically and biochemically confirmed
      hyperaldosteronism related to an adrenal adenoma, where initial screening and
      biochemical tests were potentially misleading. The case highlights the importance
      of clinical suspicion in the current diagnostic approach to primary
      hyperaldosteronism.

PMID- 28494488
TI  - Unmet need and antenatal care.

PMID- 28494489
TI  - Coeliac disease and fertility in New Zealand women.

PMID- 28494490
TI  - Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change
      Assessed by Optical Coherence Tomography in Glaucoma Eyes.
AB  - Purpose: The purpose of this study was to measure change in anterior lamina
      cribrosa depth (ALD) globally and regionally in glaucoma eyes at different
      intraocular pressures (IOP). Methods: Twenty-seven glaucoma patients were imaged
      before and after IOP-lowering procedures using optical coherence tomography. The
      anterior lamina was marked in approximately 25 locations in each of six radial
      scans to obtain global and regional estimates of ALD. ALD and its change with IOP
      were compared with optic disc damage, nerve fiber layer thickness, and visual
      field loss. Results: Variables associated with deeper baseline ALD included
      larger cup/disc ratio, thinner rim area, larger cup volume, thinner central
      corneal thickness, and male sex (all P <= 0.02). When IOP was lowered, ALD
      position became more anterior, more posterior, or was unchanged. The mean ALD
      change after lowering was 27 +/- 142 MUm (P = 0.3). The mean absolute value of
      ALD change was 112 +/- 90 MUm (P = 0.002). Change in ALD was greater in eyes with
      lower IOP in paired comparisons (P = 0.006) but was not associated with the
      magnitude of IOP lowering between imaging sessions (P = 0.94). Eyes with no
      significant change in ALD tended to have more visual field loss than those with
      significant anterior ALD displacement (P = 0.07). Areas within each optic nerve
      head that corresponded to zones with thicker nerve fiber layer had greater ALD
      positional change (P = 0.0007). Conclusions: The lamina can move either
      anteriorly or posteriorly with IOP decrease, with greater displacement at lower
      IOP. Glaucoma eyes and regions within glaucoma eyes associated with greater
      glaucoma damage exhibited smaller responses.

PMID- 28494491
TI  - Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell
      Penetrating Peptides.
AB  - Purpose: To evaluate the efficacy of anti-VEGF agents for treating choroidal
      neovascularization (CNV) when delivered topically using novel cell-penetrating
      peptides (CPPs) compared with delivery by intravitreal (ivit) injection. Methods:
      CPP toxicity was investigated in cell cultures. Ivit concentrations of
      ranibizumab and bevacizumab after topical administration were measured using
      ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared
      with ivit anti-VEGF injections using an established model of CNV. Results: CPPs
      were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were
      present in the rat anterior chamber within 6 minutes. A single application of CPP
      + bevacizumab eye drop delivered clinically relevant concentrations of
      bevacizumab to the posterior chamber of the rat eye in vivo. Similarly,
      clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were
      detected in the porcine vitreous and retina ex vivo. In an established model of
      CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily
      CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had
      significantly reduced areas of CNV when compared with lasered eyes without
      treatment. Conclusions: CPPs are nontoxic to ocular cells and can be used to
      deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop
      to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug
      complexes were cleared from the retina within 24 hours, suggesting a daily eye
      drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as
      efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in
      vivo.

PMID- 28494492
TI  - Biomechanical Differences Between Femtosecond Lenticule Extraction (FLEx) and
      Small Incision Lenticule Extraction (SmILE) Tested by 2D-Extensometry in Ex Vivo
      Porcine Eyes.
AB  - Purpose: To evaluate the biomechanical stability of ex vivo porcine corneas after
      femtosecond lenticule extraction (FLEx) and small incision lenticule extraction
      (SmILE) refractive surgeries. Methods: Forty-five porcine eyes were equally
      divided into three groups: Groups 1 and 2 were treated with FLEx and SmILE
      procedure, respectively. Group 3 served as control. A refractive correction of 
      14 diopters (D) with a 7-mm zone using either a 160-MUm flap (FLEx) or a 160-MUm
      cap (SmILE) was performed. For two-dimensional (2D) elastic and viscoelastic
      biomechanical characterization, two testing cycles (preconditioning stress-strain
      curve from 1.27 to 12.5 N, stress-relaxation at 12.5 N during 120 seconds) were
      conducted. Young's modulus and Prony constants were calculated. Results: At 0.8%
      of strain, FLEx (370 +/- 36 kPa) could resist a significantly lower stress than
      SmILE (392 +/- 19 kPa, P = 0.046) and the control group (402 +/- 30 kPa, P =
      0.013). Also, FLEx (46.1 +/- 4.5 MPa) had a significantly lower Young's modulus
      than the control group (50.2 +/- 3.4 MPa, P = 0.008). The Young's modulus of
      SmILE (48.6 +/- 2.5 MPa) had values situated between untreated corneas and FLEx
      treated corneas. When compared to untreated controls, the stress resistance
      decreased by 8.0% with FLEx and 2.5% with SmILE; Young's modulus decreased by
      5.1% with FLEx and 1.04% with SmILE. With a cap-based procedure, both anterior
      cap and stromal bed carry the intraocular pressure, while in a flap-based
      procedure, only the stromal bed does. Conclusions: Compared to flap-based
      procedures like FLEx, the cap-based technique SmILE can be considered superior in
      terms of biomechanical stability, when measured experimentally in ex vivo porcine
      corneas.

PMID- 28494493
TI  - Flexible Optical Waveguides for Uniform Periscleral Cross-Linking.
AB  - Purpose: Scleral cross-linking (SXL) with a photosensitizer and light is a
      potential strategy to mechanically reinforce the sclera and prevent progressive
      axial elongation responsible for severe myopia. Current approaches for light
      delivery to the sclera are cumbersome, do not provide uniform illumination, and
      only treat a limited area of sclera. To overcome these challenges, we developed
      flexible optical waveguides optimized for efficient, homogeneous light delivery.
      Methods: Waveguides were fabricated from polydimethylsiloxane elastomer. Blue
      light (445 nm) is coupled into the waveguide with an input fiber. Light delivery
      efficiency from the waveguide to scleral tissue was measured and fit to a
      theoretical model. SXL was performed on fresh porcine eyes stained with 0.5%
      riboflavin, using irradiances of 0, 25, and 50 mW/cm2 around the entire equator
      of the eye. Stiffness of scleral strips was characterized with tensiometry.
      Results: Light delivery with a waveguide of tapered thickness (1.4-0.5 mm)
      enhanced the uniformity of light delivery, compared to a flat waveguide,
      achieving a coefficient of variation of less than 10%. At 8% strain, sclera cross
      linked with the waveguides at 50 mW/cm2 for 30 minutes had a Young's modulus of
      10.7 +/- 1.0 MPa, compared to 5.9 +/- 0.5 MPa for no irradiation, with no
      difference in stiffness between proximally and distally treated halves. The
      stiffness of waveguide-irradiated samples did not differ from direct irradiation
      at the same irradiance. Conclusions: We developed flexible waveguides for
      periscleral cross-linking. We demonstrated efficient and uniform stiffening of a
      5-mm-wide equatorial band of scleral tissue.

PMID- 28494494
TI  - Multifocal ERG Responses in Subjects With a History of Preterm Birth.
AB  - Purpose: The purpose of this study is to assess cone-mediated central retinal
      function in children with a history of preterm birth, including subjects with and
      without retinopathy of prematurity (ROP). The multifocal electroretinogram
      (mfERG) records activity of the postreceptor retinal circuitry. Methods: mfERG
      responses were recorded to an array of 103 hexagonal elements that subtended 43
      degrees  around a central fixation target. The amplitude and latency of the first
      negative (N1) and first positive (P1) response were evaluated in six concentric
      rings centered on the fovea. Responses were recorded from 40 subjects with a
      history of preterm birth (severe ROP, mild ROP, no ROP) and 19 term-born control
      subjects. Results: The amplitude of N1 and P1 varied significantly with
      eccentricity and ROP severity. For all four groups, these amplitudes were largest
      in the center and decreased with eccentricity. At all eccentricities, N1
      amplitude was significantly smaller in severe ROP and did not differ
      significantly among the other three groups (mild ROP, no ROP, term-born
      controls). P1 amplitude in all preterm groups was significantly smaller than in
      controls; P1 amplitude was similar in no ROP and mild ROP and significantly
      smaller in severe ROP. Conclusions: These results provide evidence that premature
      birth alone affects cone-mediated central retinal function and that the magnitude
      of the effect varies with severity of the antecedent ROP. The lack of difference
      in mfERG amplitude between the mild and no ROP groups is evidence that the effect
      of ROP on the neurosensory retina may not depend solely on appearance of abnormal
      retinal vasculature.

PMID- 28494495
TI  - Mutations in LRP5,FZD4, TSPAN12, NDP, ZNF408, or KIF11 Genes Account for 38.7% of
      Chinese Patients With Familial Exudative Vitreoretinopathy.
AB  - Purpose: Familial exudative vitreoretinopathy (FEVR) is a severe hereditary
      retinal disorder characterized by defects in retinal vascular development. To
      date, six genes have been reported to be responsible for this disease, including
      LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to
      investigate the genetic defects in Chinese patients with FEVR through mutational
      analyses of 31 pedigrees. Methods: Clinical data and peripheral blood were
      collected from 31 pedigrees with FEVR. All coding sequences and intron/exon
      junctions were amplified and sequenced comprehensively, followed by cosegregation
      testing to verify suspected variants in the family members. Finally, we assessed
      clinical relevance of the identified mutations, according to the standards and
      guidelines from the American College of Medical Genetics and Genomics. Results:
      Twelve index cases (12/31, 38.7%) were confirmed to harbor mutations in the known
      genes, including one previously reported mutation and 11 novel mutations. Among
      the detected mutations, LRP5 accounted for the largest proportion with a mean
      mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31,
      6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were
      predicted to be pathogenic by a series of bioinformatics analyses. Conclusions:
      We comprehensively screened six known disease-causing genes in 31 pedigrees with
      FEVR and achieved a clear picture of the mutation spectrum in Chinese patients
      with FEVR, which highlights the importance and utility of clinical genetic
      diagnosis.

PMID- 28494496
TI  - Sensitivity to Binocular Disparity is Reduced by Mild Traumatic Brain Injury.
AB  - Purpose: The impairment of visual functions is one of the most common complaints
      following mild traumatic brain injury (mTBI). Traumatic brain injury-associated
      visual deficits include blurred vision, reading problems, and eye strain. In
      addition, previous studies have found evidence that TBI can diminish early
      cortical visual processing, particularly for second-order stimuli. We
      investigated whether cortical processing of binocular disparity is also affected
      by mTBI. Methods: In order to investigate the influence of mTBI on global
      stereopsis, we measured the quick Disparity Sensitivity Function (qDSF) in 22
      patients with mTBI. Patients with manifest strabismus and double vision were
      excluded. Compared with standard clinical tests, the qDSF is unique in that it
      offers a quick and accurate estimate of thresholds across the whole spatial
      frequency range. Results: Results show that disparity sensitivity in the mTBI
      patients were significantly reduced compared with the normative dataset (n = 61).
      The peak spatial frequency was not affected. Conclusions: Our results suggest
      that the reduced disparity sensitivity in patients with mTBI is more likely
      caused by cortical changes (e.g., axonal shearing, or reduced interhemispheric
      communication) rather than oculomotor dysfunction.

PMID- 28494497
TI  - Effect of Anatomical and Developmental Factors on the Risk of Unplanned
      Extubation in Critically Ill Newborns.

PMID- 28494498
TI  - Antenatal Exposure to Magnesium Sulfate and Spontaneous Intestinal Perforation
      and Necrotizing Enterocolitis in Extremely Preterm Neonates.

PMID- 28494499
TI  - ?
AB  - The present study aimed to evaluate the diagnostic value of echocardiography in
      measuring the thickness of epicardial adipose tissue (EAT) of the patients of
      type 2 diabetes mellitus (T2DM) and its correlation with the intimal-medial
      thickness of the carotid artery (cIMT) to investigate the relationship between
      EAT and cIMT. 68 patients of T2DM were enrolled and were divided into 2 groups:
      group of T2DM with duration<=10 years (35 cases) and group of T2DM with
      duration>10 years (33 cases). And 30 healthy subjects were enrolled as the
      control group. The thickness of EAT and cIMT were measured by echocardiography
      and high-frequency ultrasonography. The thickness of EAT and IMT of the carotid
      artery of 2 type 2 diabetic groups (duration<=10 years and>10 years) were
      significantly higher than that of the control group (all p<0.05), and the
      thickness of EAT and cIMT of the group of T2DM with duration>10 years were
      significantly higher than that of the group of T2DM with duration<=10 years
      (p<0.05). In univariate analysis, the thickness of EAT was positively and
      significantly associated with age (r=0.412, p<0.05), BMI (r=0.566, p<0.05), waist
      circumference (r=0.475, p<0.05), LDL (r=0.425, p<0.05), TG (r=0.496, p<0.05),
      duration of diabetes (r=0.384, p<0.05) and cIMT (r=0.456, p<0.05). In multiple
      stepwise regression analyses, age, BMI and IMT of carotid artery were appeared to
      be significantly associated with EAT (p<0.05 for all). In conclusion, routine
      screening of EAT and cIMT by ultrasonography in type 2 diabetic patients helps us
      to predict cardiovascular risks and prevent further development of cardiovascular
      complications.

PMID- 28494500
TI  - ?
AB  - Metabolic syndrome (MetS) consist in a combination of cardiovascular risk factors
      including elevated blood pressure, dyslipidemia, insulin resistance,
      hyperglycemia and abdominal obesity. Exercise performed before, during and after
      pregnancy can exert positive effects to counteract MetS risk factors. Here this
      review aims to analyze the effects of exercise performed before (fathers and
      mothers) and after periconception (mothers) by using experimental models and its
      effects on MetS risk factors in offspring. All selected studies investigated the
      effects of aerobic exercise before, during and after periconception on MetS risk
      factors in offspring, while no studies utilizing resistance exercise were found.
      Exercise performed before, and after periconception exerted preventive effects in
      the offspring, with regards to MetS risk factors. However, more studies focusing
      on the dose-response of exercise before, and after periconception may reveal
      interesting results on MetS risk factor in offspring. Thus, the prevention from
      chronic degenerative diseases can be improved by mother exercise and might be
      associated with epigenetic mechanisms, such as DNA methylation, hPTMs (histone
      post translational modifications), non-coding RNAs (ex: MicroRNAs) which results
      phenotypic modifications by individual genome reprograming. Otherwise, results
      from paternal exercise are inconclusive at this time.

PMID- 28494501
TI  - European Pediatric Surgical Training.

PMID- 28494502
TI  - Role of New Media for the Young Pediatric Surgeon: Fighting Exponential Knowledge
      Growth with Moore's Law.

PMID- 28494503
TI  - Leadership in Pediatric Surgery from a Trainee's Perspective.

PMID- 28494504
TI  - Metabolic Syndrome and Aggressive Prostate Cancer at Initial Diagnosis.
AB  - Links between metabolic syndrome and prostate cancer after androgen deprivation
      therapy are emerging. The aim of the research was to investigate the association
      of metabolic syndrome and aggressive prostate malignancy, at initial diagnosis,
      without the influence of hormonal treatment. Retrospective analysis of 133
      patients with prostate tumor diagnosis between 2007 and 2009 was conducted.
      Patients with prostate cancer were subdivided in 2 groups according to Gleason
      score: Gleason score>=7 as high-grade prostate tumor (Group 1) and <7 (Group 2)
      as low-grade prostate tumor. Metabolic syndrome was defined according to
      International Diabetes Federation and the American Heart Association/National
      Heart, Lung, and Blood Institute definition. Metabolic syndrome was significantly
      associated with aggressive prostate cancer (OR 1.87, p<0.05) and a reduced risk
      of low-grade prostate cancer (OR 0.53, p<0.05) at initial diagnosis, without the
      influence of endocrine therapy. In our study, patients with metabolic syndrome
      were more likely to present with more aggressive prostate carcinoma vs. patients
      without metabolic syndrome. Further research should elucidate these relations in
      larger samples to confirm these associations and to stabilize future prevention
      and therapeutic strategies.

PMID- 28494505
TI  - Genome-wide analysis of somatic copy number alterations and chromosomal breakages
      in osteosarcoma.
AB  - Osteosarcoma (OS) is the most common primary malignant bone tumor in children and
      adolescents. It is characterized by highly complex karyotypes with structural and
      numerical chromosomal alterations. The observed OS-specific characteristics in
      localization and frequencies of chromosomal breakages strongly implicate a
      specific set of responsible driver genes or a specific mechanism of fragility
      induction. In this study, a comprehensive assessment of somatic copy number
      alterations (SCNAs) was performed in 160 OS samples using whole-genome CytoScan
      High Density arrays (Affymetrix, Santa Clara, CA). Genes or regions frequently
      targeted by SCNAs were identified. Breakage analysis revealed OS specific
      unstable regions in which well-known OS tumor suppressor genes, including TP53,
      RB1, WWOX, DLG2 and LSAMP are located. Certain genomic features, such as
      transposable elements and non-B DNA-forming motifs were found to be significantly
      enriched in the vicinity of chromosomal breakage sites. A complex breakage
      pattern-chromothripsis-has been suggested as a widespread phenomenon in OS. It
      was further demonstrated that hyperploidy and in particular chromothripsis were
      strongly correlated with OS patient clinical outcome. The revealed OS-specific
      fragility pattern provides novel clues for understanding the biology of OS.

PMID- 28494507
TI  - Subepidermal moisture detection of pressure induced tissue damage on the trunk:
      The pressure ulcer detection study outcomes.
AB  - We examined the relationship between subepidermal moisture measured using surface
      electrical capacitance and visual skin assessment of pressure ulcers at the trunk
      location (sacral, ischial tuberosities) in 417 nursing home residents residing in
      19 facilities. Participants were on average older (mean age of 77 years), 58%
      were female, over half were ethnic minorities (29% African American, 12% Asian
      American, and 21% Hispanic), and at risk for pressure ulcers (mean score for
      Braden Scale for Predicting Pressure Ulcer Risk of 15.6). Concurrent visual
      assessments and subepidermal moisture were obtained at the sacrum and right and
      left ischium weekly for 16 weeks. Visual assessment was categorized as normal,
      erythema, stage 1 pressure ulcer, Deep Tissue Injury or stage 2+ pressure ulcer
      using the National Pressure Ulcer Advisory Panel 2009 classification system.
      Incidence of any skin damage was 52%. Subepidermal moisture was measured with a
      dermal phase meter where higher readings indicate greater moisture (range: 0-70
      tissue dielectric constant), with values increasing significantly with the
      presence of skin damage. Elevated subepidermal moisture values co-occurred with
      concurrent skin damage in generalized multinomial logistic models (to control for
      repeated observations) at the sacrum, adjusting for age and risk. Higher
      subepidermal moisture values were associated with visual damage 1 week later
      using similar models. Threshold values for subepidermal moisture were compared to
      visual ratings to predict skin damage 1 week later. Subepidermal moisture of 39
      tissue dielectric constant units predicted 41% of future skin damage while visual
      ratings predicted 27%. Thus, this method of detecting early skin damage holds
      promise for clinicians, especially as it is objective and equally valid for all
      groups of patients.

PMID- 28494508
TI  - Look into my eyes: An unusual first presentation of sickle cell disease.

PMID- 28494506
TI  - Minimal residual disease eradication with epigenetic therapy in core binding
      factor acute myeloid leukemia.
AB  - Recurrent translocations, t(8;21) or inv(16), in core binding factor acute
      myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual
      disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR).
      Despite a favorable prognosis, disease relapse remains the single cause of
      treatment failure in CBF-AML. Fusion products of these translocations recruit
      epigenetic silencing complexes resulting in hematopoietic maturation arrest. We
      hypothesized that maintenance therapy with hypomethylating agents (HMA),
      including decitabine (DAC) and azacitidine (AZA) after induction/consolidation,
      can be used for MRD elimination to ultimately prolong relapse free survival. Real
      time quantitative (RTPCR) trends were reviewed in 23 patients (median age 53
      years) with CBF-AML that received HMA therapy following induction/consolidation
      with fludarabine, cytarabine, and G-CSF (FLAG) with low dose gemtuzumab or
      idarubicin (NCT00801489). Of the 23 patients evaluated, 17 had a detectable RTPCR
      at HMA initiation. Five patients had progressive disease and a notable increase
      in RTPCR values over 1-2 cycles of HMA therapy. Twelve patients did not fail HMA
      and had a median RTPCR at HMA initiation of 0.06 (range, 0.01-0.91). Unlike the
      HMA failure subset, 11 of these patients had a reduction in RTPCR after the first
      or second cycle of HMA. Our data suggests that CBF-AML patients with low levels
      of RTPCR (between 0.01 and 0.05) at the conclusion of induction/consolidation
      chemotherapy benefit most from maintenance HMA, particularly those that have a
      reduction in the RTPCR within the first two cycles of HMA therapy.

PMID- 28494509
TI  - Estimates of total body iron indicate 19 mg and 38 mg oral iron are equivalent
      for the mitigation of iron deficiency in individuals experiencing repeated
      phlebotomy.
AB  - Iron deficiency anemia is a common clinical condition often treated with tablets
      containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side
      effects lowering patient compliance. Oral iron supplements also increase hepcidin
      production causing decreased fractional absorption of subsequent doses. Frequent
      blood donors often become iron deficient. Therefore, they were enrolled in a two
      year study involving continued blood donations and randomization to receive no
      pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI)
      did not change for the subset of donors in the no pill and placebo groups who
      completed both enrollment and final visits (P = .21 and P = .28, respectively).
      However, repeated measures regression analysis on the complete dataset estimated
      a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (P
      = .001). The effects of 19 and 38 mg iron supplementation on TBI were
      indistinguishable (P = .54). TBI increased by 229 mg after the initial 60 days of
      iron supplementation (P < .0001) and was maintained at this higher level with
      continued iron supplementation following each subsequent donation. The TBI
      increase was apportioned 51 mg to red cell iron (P < .0001) and 174 mg to storage
      iron (P < .0001). Changes in storage iron were negatively impacted by 57 mg due
      to concurrent antacid use (P = .04). These findings in blood donors suggest that
      much lower doses of iron than are currently used will be effective for clinical
      treatment of iron deficiency anemia.

PMID- 28494510
TI  - Response to 'Colorectal cancer resection in the Australian nonagenarian patient'.

PMID- 28494511
TI  - The ethnic distribution of sessile serrated polyps in the United States is
      inversely associated with Helicobacter pylori prevalence.
AB  - AIM: Little is known about the epidemiology of sessile serrated polyps (SSP). Our
      study aimed to investigate the influence of Helicobacter pylori gastritis and
      patient demographic characteristics (age, gender, ethnicity) on the prevalence of
      SSP using a large national database of patients undergoing bi-directional
      endoscopy. METHOD: De-identified patient data were extracted from the Miraca Life
      Sciences electronic database of histopathological reports. Using multivariate
      logistic regression analysis, the influence of H. pylori gastritis and
      demographic characteristics on the occurrence of SSP were expressed as odds
      ratios (OR) with their 95% confidence intervals (CI). RESULTS: The total study
      population comprised 228 506 subjects, of whom 28 890 carried a diagnosis of H.
      pylori gastritis and 11 285 SSP. Age (OR 4.35, 95% CI: 3.82-4.96), female gender
      (0.92, 0.88-0.95) and H. pylori gastritis (0.94, 0.88-0.99) exerted the strongest
      influence on the occurrence of SSP. In comparison with the population comprising
      Caucasians and African Americans, SSP were less common among subjects of Hispanic
      (0.67, 0.62-0.73), East Asian (0.59, 0.50-0.69), Indian (0.43, 0.27-0.64) or
      Middle Eastern descent (0.61, 0.41-0.87). All these ethnic subgroups were also
      characterized by a higher prevalence of H. pylori than the comparison group. A
      low prevalence of H. pylori was significantly associated with a high prevalence
      of SSP (R2  = 0.82, P < 0.001). CONCLUSION: The prevalence of SSP within the
      United States is characterized by a marked ethnic variation. The inverse
      correlation between the prevalence of H. pylori and SSP suggests that gastric
      infection with H. pylori may be partly responsible for the observed ethnic
      distribution of SSP.

PMID- 28494512
TI  - Gene expression profiling of skeletal muscle after volumetric muscle loss.
AB  - Volumetric muscle loss (VML), usually occurring following traumatic injury,
      results in a composite loss of muscle mass. These injuries manifest as decreased
      strength and functional impairments. Clinically, these injuries often heal with
      fibrosis, as opposed to skeletal muscle regeneration. This study examines the
      healing patterns of a skeletal muscle following VML in a murine model. Eight-week
      old male C57BL/6J mice used in the study underwent either bilateral VML injury or
      cryoinjury, a widely used model known to induce skeletal muscle regeneration.
      Skeletal muscle was harvested at 2 and 4 weeks following injury and subjected to
      histological analysis. H&E staining demonstrated skeletal muscle regeneration
      following cryoinjury, but not VML, at either timepoint post-injury. Additionally,
      samples were analyzed using a wound-healing PCR array to identify differentially
      regulated genes of interest in VML and cryoinjury, as compared to noninjured
      controls. The gene array data further demonstrated prolonged inflammation and
      increased pro-fibrotic activity in the VML injured muscles, as compared to
      cryoinjury. In addition, IGF1, a known myogenic factor, was significantly
      decreased following VML, as compared to cryoinjury, in both ELISA and PCR. This
      study offers an insight into the pathophysiology of VML injury and reveals a gene
      profile of a nonregenerating skeletal muscle.

PMID- 28494513
TI  - Patients with 'interval' colorectal cancers have worse outcomes compared with
      cancers in patients who decline the National Bowel Cancer Screening Programme -
      Results from a Multicentre Study.

PMID- 28494514
TI  - Urinary prednisolone excretion is a determinant of serum hepcidin levels in renal
      transplant recipients.

PMID- 28494515
TI  - Potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1
      labeled with carbon-13 and carbon-14.
AB  - (S)-6-(2-Hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4
      yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (1) and (4aR,9aS)-1-(1H
      benzo[d]midazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1-H-indeno[2,1-b]pyridine-6
      carbonitrile hydrochloride (2) are potent and selective inhibitor of 11beta
      hydroxysteroid dehydrogenase type 1 enzyme. These 2 drug candidates developed for
      the treatment of type-2 diabetes were prepared labeled with carbon-13 and carbon
      14 to enable drug metabolism, pharmacokinetics, bioanalytical, and other studies.
      In the carbon-13 synthesis, benzoic-13 C6 acid was converted in 7 steps and in
      16% overall yield to [13 C6 ]-(1). Aniline-13 C6 was converted in 7 steps to 1H
      benzimidazole-1-2,3,4,5,6-13 C6 -5-carboxylic acid and then coupled to a
      tricyclic chiral indenopiperidine to afford [13 C6 ]-(2) in 19% overall yield.
      The carbon-14 labeled (1) was prepared efficiently in 2 radioactive steps in 41%
      overall yield from an advanced intermediate using carbon-14 labeled methyl
      magnesium iodide and Suzuki-Miyaura cross coupling via in situ boronate
      formation. As for the synthesis of [14 C]-(2), 1H-benzimidazole-5-carboxylic-14 C
      acid was first prepared in 4 steps using potassium cyanide-14 C, then coupled to
      the chiral indenopiperidine using amide bond formation conditions in 26% overall
      yield.

PMID- 28494516
TI  - The Modulation of the Startle Reflex as Predictor of Alcohol Use Disorders in a
      Sample of Heavy Drinkers: A 4-Year Follow-Up Study.
AB  - BACKGROUND: Previous studies demonstrated that patients with alcohol use
      disorders (AUDs) show altered startle reflex responses to alcohol-related
      stimuli. However, there is little information about the role of these altered
      responses in the development of AUDs. This study examined the startle reflex
      response to different visual stimuli and the role of these patterns in the
      development of AUDs in a 4-year follow-up. METHODS: Two hundred and thirty-nine
      (nondependent) heavy-drinking participants were selected. In the baseline period,
      the startle reflex responses to alcohol-related, aversive, appetitive, and
      neutral pictures were assessed. Startle reflex responses to these pictures were
      used as predictive variables. Status drinking (alcohol dependence and
      nondependence) assessed at 4-year follow-up was used as outcome measure. RESULTS:
      At the 4-year follow-up assessment, 46% of participants fulfilled DSM-IV alcohol
      abuse or dependence criteria. Alcohol dependence status was predicted by an
      attenuated startle reflex response to alcohol-related and aversive pictures.
      CONCLUSIONS: This study revealed that an attenuated modulation of startle reflex
      response to alcohol-related and aversive stimuli could be used as a clinical
      marker to predict the development of AUDs in participants with previous alcohol
      consumption.

PMID- 28494517
TI  - Exploration of peripapillary vessel density in highly myopic eyes with
      peripapillary intrachoroidal cavitation and its relationship with ocular
      parameters using optical coherence tomography angiography.
AB  - IMPORTANCE: Identifying changes of peripapillary vessel density in highly myopic
      eyes with peripapillary intrachoroidal cavitation by optical coherence tomography
      angiography. BACKGROUND: To investigate peripapillary vessel density and its
      relationship with other ocular parameters in highly myopic eyes with
      peripapillary intrachoroidal cavitation. DESIGN: Hospital-based, cross-sectional
      study. PARTICIPANTS: Thirty-five highly myopic eyes with peripapillary
      intrachoroidal cavitation, 46 highly myopic eyes without peripapillary
      intrachoroidal cavitation and 36 normal eyes were included in this study.
      METHODS: All participants underwent optical coherence tomography angiography to
      image the retinal vasculature in the peripapillary areas, including the radial
      peripapillary capillaries and optic nerve head layer. Correlations between vessel
      density and ocular metrics were analysed. MAIN OUTCOME MEASURES: Peripapillary
      vessel density. RESULTS: In highly myopic eyes, vessel density was significantly
      lower in eyes with peripapillary intrachoroidal cavitation than in those without
      in peripapillary (P = 0.014, P = 0.037), inferotemporal (P < 0.001, P < 0.001)
      and superotemporal (P = 0.014, P = 0.009) areas. In the radial peripapillary
      capillaries layer, vessel density was negatively correlated with peripapillary
      atrophy area (P = 0.012) and myopic maculopathy (P = 0.002), and in the optic
      nerve head layer, it was negatively associated with a diagnosis of peripapillary
      intrachoroidal cavitation (P = 0.012) and myopic maculopathy (P < 0.001). In
      addition, it was positively correlated with retinal nerve fibre layer thickness
      in both layers (P < 0.001). CONCLUSIONS AND RELEVANCE: Highly myopic eyes with
      peripapillary intrachoroidal cavitation had lower peripapillary vessel densities,
      especially in the temporal area, than those without.

PMID- 28494518
TI  - Correlates of resistance and relapse during blinatumomab therapy for
      relapsed/refractory acute lymphoblastic leukemia.
AB  - We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who
      were treated with blinatumomab for predictors of leukemia response as well as
      clinical patterns of relapse and resistance with particular focus on
      downregulation of CD19 expression and extramedullary disease (EM-ALL). The
      complete remission (CR) rate was 51%, and 15 (45%) responders underwent
      allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden
      (bone marrow blasts >50%) (P = .02), history of prior EM-ALL (P = .005), and
      active EM-ALL at the time of initiating blinatumomab (P = .05) predicted lower CR
      rate. Among refractory cases, 13 (41%) had evidence of EM-ALL progression, and
      CD19 expression was negative or dim in 18% and 23%, respectively. Among
      responders, 20 (61%) subsequently relapsed among whom EM-ALL relapse occurred in
      8 (40%) patients, and CD19 expression was negative or dim in 35 and 6% of
      evaluable cases, respectively. Pretreatment moderate/strong CD19 expression (P =
      .01) and history of prior EM-ALL during ALL course (P = .04) were risk factors
      for developing EM-ALL at progression/relapse. However, no pretreatment factors
      predicted progression/relapse with CD19-negative ALL. Overall-survival (OS) and
      even-free survival were improved for patients underwent allogeneic HCT compared
      to responders who did not. Furthermore, OS was superior for patients responded to
      blinatumomab compared to those who did not. Extramedullary and CD19-negative
      disease are common during blinatumomab failure in r/r ALL. In addition to high
      leukemia burden, concurrent or prior history EM-ALL were associated with lower
      response to blinatumomab. Higher CD19 expression as well as prior history of EM
      ALL were associated with EM-ALL at the time of blinatumomab failure.

PMID- 28494519
TI  - Molecular insights into Cassava brown streak virus susceptibility and resistance
      by profiling of the early host response.
AB  - Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV)
      are responsible for significant cassava yield losses in eastern sub-Saharan
      Africa. To study the possible mechanisms of plant resistance to CBSVs, we
      inoculated CBSV-susceptible and CBSV-resistant cassava varieties with a mixed
      infection of CBSVs using top-cleft grafting. Transcriptome profiling of the two
      cassava varieties was performed at the earliest time point of full infection (28
      days after grafting) in the susceptible scions. The expression of genes encoding
      proteins in RNA silencing, salicylic acid pathways and callose deposition was
      altered in the susceptible cassava variety, but transcriptional changes were
      limited in the resistant variety. In total, the expression of 585 genes was
      altered in the resistant variety and 1292 in the susceptible variety.
      Transcriptional changes led to the activation of beta-1,3-glucanase enzymatic
      activity and a reduction in callose deposition in the susceptible cassava
      variety. Time course analysis also showed that CBSV replication in susceptible
      cassava induced a strong up-regulation of RDR1, a gene previously reported to be
      a susceptibility factor in other potyvirus-host pathosystems. The differences in
      the transcriptional responses to CBSV infection indicated that susceptibility
      involves the restriction of callose deposition at plasmodesmata. Aniline blue
      staining of callose deposits also indicated that the resistant variety displays a
      moderate, but significant, increase in callose deposition at the plasmodesmata.
      Transcriptome data suggested that resistance does not involve typical antiviral
      defence responses (i.e. RNA silencing and salicylic acid). A meta-analysis of the
      current RNA-sequencing (RNA-seq) dataset and selected potyvirus-host and virus
      cassava RNA-seq datasets revealed that the conservation of the host response
      across pathosystems is restricted to genes involved in developmental processes.

PMID- 28494520
TI  - Characterization of TP53 mutations in clonal cytopenia of undetermined
      significance.

PMID- 28494521
TI  - Topical 1% propranolol cream promotes cutaneous wound healing in spontaneously
      diabetic mice.
AB  - : Diabetic foot ulcers (DFUs) are a constant threat to diabetic patients and can
      lead to amputations and even death. Intralesional administration of propranolol
      in diabetic wounds has not been reported previously. This study aimed to
      investigate the efficacy of propranolol cream in diabetic wounds. Fifty-six
      spontaneously diabetic mice were divided into the propranolol group and the
      control group. After preparing full-thickness wounds on the back of the mice, 1%
      propranolol cream was topically applied to wounds in the experimental group and
      0% propranolol cream in controls. The wound sizes were measured and calculated
      against the original area. The wounds were analyzed up to 21 days after injury.
      At all evaluation time-points, the wound size (%) in the propranolol group was
      significantly smaller than in the controls. Epidermal growth factor (EGF) protein
      expression increased in the experimental vs. CONTROL GROUP: Vascular endothelial
      growth factor (VEGF) expression was significantly lower in the experimental vs.
      control group whereas NG2 proteoglycan was increased throughout the study.
      However, matrix metallopeptidase (MMP)-9 expression was at first significantly
      higher in the experimental vs. control group then the MMP-9 protein level in the
      control group increased and surpassed that in the experimental group. In
      conclusion, intralesional administration of 1% propranolol cream promotes
      reepithelialization and regulates abnormal angiogenesis in diabetic wounds.
      Propranolol cream may become a new drug for the treatment of DFUs.

PMID- 28494522
TI  - Response to Bethune et al.

PMID- 28494523
TI  - Korean Thyroid Imaging Reporting and Data System features of follicular thyroid
      adenoma and carcinoma: a single-center study.
AB  - PURPOSE: This study aimed to assess the diagnostic efficacy of Korean Thyroid
      Imaging Reporting and Data System (K-TIRADS) features for distinguishing
      follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC).
      METHODS: From January 2013 to July 2016, 46 follicular neoplasms in 45 patients
      who underwent preoperative thyroid ultrasonography (US) and thyroid surgery were
      included. The US features of each thyroid nodule were retrospectively evaluated
      by a single radiologist using a picture archiving and communication system. The
      diagnostic indices of K-TIRADS for follicular neoplasms were calculated according
      to whether K-TIRADS category 4 lesions were excluded or classified as benign or
      malignant. RESULTS: Of the 46 follicular neoplasms (mean size, 3.1+/-1.6 cm), 37
      were FTAs (mean size, 3.1+/-1.7 cm) and nine were FTCs (mean size, 3.0+/-1.5 cm).
      A statistically significant difference was found between FTAs and FTCs regarding
      the margin (P=0.035), while no significant differences were observed in the
      composition, echogenicity, shape, orientation, calcification, or vascularity of
      the lesions (P<0.05). The FTAs belonged to K-TIRADS categories 3 (n=22) and 4
      (n=15), while the FTCs belonged to K-TIRADS categories 3 (n=4), 4 (n=4), and 5
      (n=1). However, there was no statistically significant difference in the
      distribution of K-TIRADS categories between FTAs and FTCs (P=0.184). CONCLUSION:
      K-TIRADS features were not helpful for distinguishing FTA from FTC, although
      follicular neoplasms showed a high prevalence of K-TIRADS categories 3 and 4.

PMID- 28494524
TI  - Ultrasonographic findings of posterior interosseous nerve syndrome.
AB  - PURPOSE: The purpose of this study was to evaluate the ultrasonographic findings
      associated with posterior interosseous nerve (PIN) syndrome. METHODS: Approval
      from the Institutional Review Board was obtained. A retrospective review of 908
      patients' sonographic images of the upper extremity from January 2001 to October
      2010 revealed 10 patients suspicious for a PIN abnormality (7 male and 3 female
      patients; mean age of 51.8+/-13.1 years; age range, 32 to 79 years). The
      ultrasonographic findings of PIN syndrome, including changes in the PIN and
      adjacent secondary changes, were evaluated. The anteroposterior diameter of the
      pathologic PIN was measured in eight patients and the anteroposterior diameter of
      the contralateral asymptomatic PIN was measured in six patients, all at the level
      immediately proximal to the proximal supinator border. The size of the pathologic
      nerves and contralateral asymptomatic nerves was compared using the Mann-Whitney
      U test. RESULTS: Swelling of the PIN proximal to the supinator canal by
      compression at the arcade of Frohse was observed in four cases. Swelling of the
      PIN distal to the supinator canal was observed in one case. Loss of the
      perineural fat plane in the supinator canal was observed in one case. Four soft
      tissue masses were noted. Secondary denervation atrophy of the supinator and
      extensor muscles was observed in two cases. The mean anteroposterior diameter of
      the pathologic nerves (n=8, 1.79+/-0.43 mm) was significantly larger than that of
      the contralateral asymptomatic nerves (n=6, 1.02+/-0.22 mm) (P=0.003).
      CONCLUSION: Ultrasonography provides high-resolution images of the PIN and helps
      to diagnose PIN syndrome through visualization of its various causes and adjacent
      secondary changes.

PMID- 28494526
TI  - Ultrasonographic evaluation of women with pathologic nipple discharge.
AB  - Nipple discharge is a common symptom that is alarming for the patient since it
      can be a presenting symptom of breast cancer. Breast imaging is used to examine
      women with pathologic nipple discharge in order to detect any lesions that may be
      present and to assist in the differential diagnosis. The modalities of breast
      imaging include mammography, breast ultrasonography (US), and magnetic resonance
      imaging. Breast US is currently considered to be useful for the visualization of
      ductal structures and intraductal lesions that cause nipple discharge. In this
      review, we discuss US techniques that assist in the clear visualization of ductal
      structures and intraductal lesions in patients with nipple discharge. Controversy
      remains regarding the evaluation and management of patients with nipple
      discharge, and we summarize the results available in the currently published
      literature.

PMID- 28494525
TI  - Ultrasonography of pediatric urogenital emergencies: review of classic and new
      techniques.
AB  - Urogenital emergencies are fairly common in the pediatric population, and a
      timely and correct diagnosis is necessary to avoid possible future infertility.
      In this field, ultrasonography is essential, as it has the advantages of being
      radiation-free and readily accessible. In particular, a high-frequency transducer
      allows precise evaluation of the morphology and vascularity of the scrotum, which
      is on the surface of the body. Beyond conventional techniques, new advanced
      imaging techniques have been developed, including elastography and contrast
      enhanced ultrasonography. However, several pitfalls remain in the diagnosis of
      urogenital diseases using ultrasonography. Thus, accurate knowledge and
      sufficient experience with the technique are essential for making a correct
      diagnosis. This review provides an overview of pediatric urogenital emergency
      pathologies and recent ultrasonography techniques.

PMID- 28494527
TI  - Relationships Among Factors Relevant to Abdominal Fat and Age-Related Hearing
      Loss.
AB  - OBJECTIVES: Metabolic syndrome is related with abdominal fat and with age-related
      hearing loss (ARHL). In this study, we evaluated the association between a
      variety of factors relevant to abdominal fat (FRAs) and hearing thresholds.
      METHODS: We reviewed retrospectively the medical records of 2,602 subjects aged
      over 40 years with symmetrical sensorineural hearing loss who underwent abdominal
      fat computed tomography (CT) scans. Univariate and multivariate linear regression
      analyses were used to demonstrate the association between each FRA and hearing
      thresholds at low and high frequencies. RESULTS: Four of 5 FRAs were associated
      with hearing thresholds at high frequencies in males. All FRAs examined showed a
      relationship with hearing thresholds at low frequencies in females. Diabetes
      mellitus (DM) among clinical factors and visceral adipose tissue (VAT) among the
      5 FRAs were the most reflective of hearing thresholds in both males and females.
      CONCLUSION: We found that FRAs were associated with hearing loss with frequency
      specific characteristics according to sex and reinforced that DM and VAT is
      particularly an important role for hearing.

PMID- 28494528
TI  - A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic
      Liver Cancer-stage C hepatocellular carcinoma with poor liver function.
AB  - BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in
      comparatively low doses as a continuous chemotherapeutic agent. The aim of this
      study was to evaluate the feasibility and overall survival (OS) of MET compared
      to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal
      vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC
      and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53
      patients who had undergone sorafenib therapy were analyzed as the control group.
      The primary endpoint of this study was OS. RESULTS: The median number of MET
      cycles was two (1-15). The OS values for the MET group and sorafenib group were
      158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox
      proportional-hazard model showed that a higher risk of death was correlated with
      higher serum alpha fetoprotein level (>=400 mg/dL, hazard ratio [HR]=1.680,
      P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was
      associated with more favorable outcomes in terms of overall survival than was
      sorafenib in patients with advanced HCC with PVTT, especially in patients with
      poor liver function. Therefore, MET can be considered as a treatment option in
      patients with advanced HCC with PVTT and poor liver function.

PMID- 28494529
TI  - NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin
      drugs.
AB  - Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic
      fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis,
      portal hypertension and primary liver cancer. Therapy is evolving with a
      substantial number of trials of promising new agents now in progress. In this
      article however, we will examine data for several older forms of therapy which
      have been fairly extensively studied over the years: Polyunsaturated Fatty Acid
      (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on
      pioglitazone and statin agents. Early interest in PUFA derived from their
      potential benefit in cardio-metabolic disease and the close association of
      NAFLD/NASH with Metabolic Syndrome. Results have been variable although most
      studies show reduction of liver fat without other major effects and their effects
      are influenced by concomitant weight loss and underlying genetic factors. Vitamin
      E has had some efficacy in pediatric NASH but questionable efficacy in even mild
      NASH among adults. Pioglitazone has shown significant histological benefit in a
      number of trials but concern over side-effects (especially weight gain) have
      dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown
      promise in a small randomized, controlled trial. Very limited data exists
      regarding the histological effects of the statins in NASH and these agents appear
      to be fairly neutral with neither clear cut benefit nor detriment. Their use is
      best guided by cardiovascular risks rather than liver histology.

PMID- 28494530
TI  - Radioembolization for the treatment of hepatocellular carcinoma.
AB  - Transarterial radioembolization (TARE) with yttrium 90 (90Y), an intra-arterial
      procedure performed by interventional radiologists, has begun being utilized in
      managing hepatocellular carcinoma (HCC) in Korea. There are two available TARE
      products: glass and resin microspheres with different physical characteristics.
      All patients undergoing TARE must be assessed with clinical examination and
      laboratory tests as well as a thorough angiographic evaluation. TARE is safe and
      effective in the treatment of unresectable HCC, as it has longer time-to
      progression, greater ability to downsize tumors for liver transplantation, less
      post-embolization syndrome, and shorter hospitalization compared with
      chemoembolization. TARE can also serve as an alternative to ablation, surgical
      resection, portal vein embolization, and sorafenib. The utility of TARE continues
      to expand with new insights in interventional oncology.

PMID- 28494531
TI  - Stages of Adoption for Fecal Occult Blood Test and Colonoscopy Tests for
      Colorectal Cancer Screening in Korea.
AB  - PURPOSE: While colorectal cancer (CRC) is common in Asian countries, screening
      for CRC is not. Moreover, CRC screening behaviors in Asian populations remain
      largely unknown. The present study aimed to investigate the stages of adopting
      CRC screening in Korea according to screening modality. MATERIALS AND METHODS:
      Data were obtained from the 2014 Korean National Cancer Screening Survey, a cross
      sectional survey that utilized nationally representative random sampling to
      investigate cancer screening rates. A total of 2,066 participants aged 50-74
      years were included in this study. Chi-square test and multinomial logistic
      regressionwere applied to determine stages of adoption for fecal occult blood
      test (FOBT) and colonoscopy and factors associated with each stage. RESULTS: Of
      1,593 participants included in an analysis of stage of adoption for FOBT, 36%
      were in action/maintenance stages, while 18%, 40%, and 6% were in
      precontemplation, contemplation, and relapse/relapse risk stages, respectively.
      Of 1,371 subjects included in an analysis of stage of adoption for colonoscopy,
      48% were in action/maintenance stages, with 21% in precontemplation, 21% in
      contemplation, and 11% in relapse/relapse risk stages. Multinomial logistic
      regression highlighted sex, household income, place of residency, family history
      of cancer, having private cancer insurance, smoking status, alcohol use, and
      regular exercise as being associated with stages of adoption for FOBT and
      colonoscopy. CONCLUSION: This study outlines the distributions of stages of
      adoption for CRC screening by screening modality. Interventions to improve
      screening rates should be tailored to individuals in particular stages of
      adoption for CRC screening by modality.

PMID- 28494532
TI  - Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A
      Nationwide Cohort Study.
AB  - PURPOSE: Previous western studies have found Caucasians with skin cancer, either
      melanoma or nonmelanoma skin cancer (NMSC), have an elevated risk of second
      primary cancer. Our objective was to assess the risk of second primary cancer in
      Taiwanese with NMSC. MATERIALS AND METHODS: By using data from Taiwan's National
      Health Insurance Research Database, we conducted a population-based cohort study
      to assess the risk of incident second primary cancer in Taiwanese affected by
      NMSC. RESULTS: We identified 505 subjects with NMSC and 2,020 matched controls.
      After adjustment for potential confounders including age, sex, urbanization, and
      Charlson Comorbidity Index, people who had NMSC had a 1.43-fold (95% confidence
      interval [CI], 1.05 to 1.96) risk for the development of second primary cancer as
      comparedwith control group. Menwith NMSC had a 2.99-fold (95% CI, 1.00 to 9.10)
      risk for second primary cancer involving the lip, oral cavity, and pharynx and a
      3.51-fold (95% CI, 1.21 to 10.17) risk for second primary cancer involving the
      genitourinary organs when compared to the control group. By contrast, women with
      NMSC did not have an increased risk of second primary cancer. CONCLUSION: This
      study revealed Asians with NMSC have an increased risk of second primary cancer.
      Our findings can be a useful reference for health care for people diagnosed with
      NMSC.

PMID- 28494533
TI  - Awareness of and Attitudes toward Human Papillomavirus Vaccination among Adults
      in Korea: 9-Year Changes in Nationwide Surveys.
AB  - PURPOSE: Human papillomavirus (HPV) vaccination has been included in the National
      Immunization Program in Korea since 2016. We aimed to evaluate changes in the
      awareness of and attitudes toward HPV vaccination, among adults in Korea since
      the first introduction of the vaccines in 2007. MATERIALS AND METHODS: A
      nationwide population-based survey was conducted in 2016 for 1,200 nationally
      representative Korean men and women; the data obtained were compared with the
      data from the nationwide survey conducted in 2007. RESULTS: A significant
      increase in the awareness of HPV infection (35.8%) and vaccination (36.9%) was
      observed in 2016 from 13.3% and 8.6% in 2007, respectively. Willingness to be
      vaccinated against HPV decreased from 55.0% in 2007 to 25.8% in 2016, and the
      proportion of respondents expressing uncertainty increased from 28.3% in 2007 to
      43.3% in 2016. Only 12.1% of men and 22.0% of women knew about the free national
      HPV vaccination program for girls, launched in June 2016. Younger women, with
      higher income level, awareness of the HPV vaccine, and perception of the
      seriousness of infections had a higher willingness to be vaccinated. A high
      education level, awareness of HPV infection and vaccination, and perception of
      the seriousness of infection were positively associated with the willingness of
      respondents to vaccinate their daughters. CONCLUSION: Raising the awareness of
      HPV infection and vaccination with appropriate knowledge is necessary for the
      successful implementation of the national HPV vaccination program.

PMID- 28494534
TI  - Ferroptosis: A Novel Anti-tumor Action for Cisplatin.
AB  - PURPOSE: Ferroptosis is a new mode of regulated cell death, which is completely
      distinct from other cell death modes based on morphological, biochemical, and
      genetic criteria. This study evaluated the therapeutic role of ferroptosis in
      classic chemotherapy drugs, including the underlying mechanism. MATERIALS AND
      METHODS: Cell viabilitywas detected by using the methylthiazoltetrazlium dye
      uptake method. RNAiwas used to knockout iron-responsive element binding protein
      2, and polymerase chain reaction, western blot was used to evaluate the
      efficiency. Intracellular reduced glutathione level and glutathione peroxidases
      activitywere determined by related assay kit. Intracellularreactive oxygen
      species levelswere determined by flowcytometry. Electron microscopywas used to
      observe ultrastructure changes in cell. RESULTS: Among five chemotherapeutic
      drugs screened in this study, cisplatin was found to be an inducer for both
      ferroptosis and apoptosis in A549 and HCT116 cells. The depletion of reduced
      glutathione caused by cisplatin and the inactivation of glutathione peroxidase
      played the vital role in the underlying mechanism. Besides, combination therapy
      of cisplatin and erastin showed significant synergistic effect on their anti
      tumor activity. CONCLUSION: Ferroptosis had great potential to become a new
      approach in anti-tumor therapies and make up for some classic drugs, which open
      up a new way for their utility in clinic.

PMID- 28494535
TI  - TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced
      Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open
      Label, Non-randomized Phase 1 Study.
AB  - PURPOSE: This phase 1 dose-escalation portion of the study evaluated the safety,
      pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with
      advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or
      gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC).
      MATERIALS AND METHODS: Adult patients with advanced GI malignancies expressing
      GCC (H-score >= 10) received TAK-264 on day 1 of 3-week cycles as 30-minute
      intravenous infusions for up to 1 year or until disease progression or
      unacceptable toxicity. The primary objectives were to evaluate the safety profile
      including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum
      tolerated dose (MTD), and characterize the PK profile of TAK-264. RESULTS: Twelve
      patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8
      mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1
      to 10). None of the patients experienced a DLT and the MTD was not determined.
      Ten patients (83%) experienced adverse events (AEs). The most common were
      neutropenia, anorexia, and nausea (each reported by four patients). Five patients
      (42%) experienced grade >= 3 AEs consisting of tumor hemorrhage and hypertension,
      ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK
      264 increased proportionally with the dose and the median half-life was
      approximately 5.5-6.6 days. No patients experienced an objective response.
      CONCLUSION: TAK-264 demonstrated a manageable safety profile with limited
      antitumor activity consistent with studies conducted in Western patients with
      advanced GI malignancies. TAK-264 exposure increased proportionally with the
      dose.

PMID- 28494536
TI  - Clinical Significance of Discordance between Carcinoembryonic Antigen Levels and
      RECIST in Metastatic Colorectal Cancer.
AB  - PURPOSE: The purpose of this study was to investigate the prognostic implications
      of carcinoembryonic antigen (CEA) levels that are inconsistent with Response
      Evaluation Criteria in Solid Tumor (RECIST) responses in metastatic colorectal
      cancer patients. MATERIALS AND METHODS: We retrospectively evaluated 360 patients
      with at least one measurable lesion who received first-line palliative
      chemotherapy. CEA-response was defined as CEA-complete response (CR; CEA
      normalization), CEA-partial response (PR; >= 50% decrease in CEA levels), CEA
      progressive disease (PD; >= 50% increase in CEA levels), and CEA-stable disease
      (SD; non-CR/PR/PD). Overall survival (OS) and progression-free survival (PFS)
      were evaluated according to CEA-response. RESULTS: In RECIST-PR patients, poorer
      CEA-response was associated with disease progression at the subsequent
      evaluation. In RECIST-SD patients, CEA-CR and -PR were associated with lower
      disease progression rates than CEA-PD at the subsequent evaluation. Correlations
      between survival outcome and CEA-response in same-category RECIST patients were
      assessed. In RECIST-PR patients, discordant CEA-response (CEA-PD/SD) was
      associated with poorer survival than CEA-CR/PR (median OS and PFS, 44.0 and 15.4
      [CEA-CR], 28.9 and 12.5 [CEA-PR], 21.0 and 9.8 [CEA-SD], and 13.0 and 7.0 [CEA
      PD] months, respectively; all p < 0.001). In RECIST-SD patients, favorable CEA
      response produced better survival (median OS and PFS, 26.8 and 21.0 [CEA-CR],
      21.0 and 11.0 [CEA-PR], 16.1 and 8.2 [CEA-SD], and 12.2 and 6.0 [CEA-PD] months,
      respectively; all p < 0.001). RECIST-PD patients with CEA-CR showed longer OS
      than those with CEA-PD. Multivariate analysis demonstrated that discordant CEA
      response is a powerful prognostic factor for RECIST-PR and RECIST-SD patients.
      CONCLUSION: Among patients of the same RECIST-response categories, CEA-response
      patterns are significantly prognostic and strongly predictive of subsequent
      evaluation outcomes.

PMID- 28494537
TI  - Interstitial Lung Disease and Lung Cancer Development: A 5-Year Nationwide
      Population-Based Study.
AB  - PURPOSE: In this nationwide 5-year longitudinal population-based study, we aimed
      at investigating the incidence of lung cancer among patients with interstitial
      lung disease. MATERIALS AND METHODS: Data was collected from the Korean National
      Health Insurance Research Database from 49,773,195 Korean residents in 2009.
      Thirteen thousand six hundred and sixty-six patients with interstitial lung
      disease diagnosed January-December 2009. The end of follow-up was June 30, 2014.
      Up to four matching chronic obstructive pulmonary disease controls were selected
      to compare the lung cancer high-risk group based on age, sex, diagnosis date
      (within 30 days), and hospital size. The number of patients with newly developed
      lung cancer was determined. RESULTS: The incidences of lung cancer were 126.98,
      156.62, and 370.38 cases per 10,000 person-years (2,732, 809, and 967 cases of
      cancer, respectively) in the chronic obstructive pulmonary disease, interstitial
      lung disease, and chronic obstructive pulmonary disease with interstitial lung
      disease groups, respectively. Of the 879 patients with idiopathic pulmonary
      fibrosis, 112 developed lung cancer (incidence, 381.00 cases per 10,000 person
      years). CONCLUSION: Incidence of lung cancer among patients with interstitial
      lung disease was high. Interstitial lung diseases have a high potential for
      developing into lung cancer, even when concurrent with chronic obstructive
      pulmonary disease.

PMID- 28494538
TI  - The exposome and the future of epidemiology: a vision and prospect.
AB  - It is widely accepted that a relatively small proportion of chronic disease can
      be explained by genetic factors alone. Although information about environmental
      exposure is important to comprehensively evaluate chronic diseases, this
      information is not sufficiently or accurately assessed by comparison with genomic
      factors. To emphasize the importance of more complete evaluation of environmental
      exposure, the concept of the exposome, which indicates the entirety of
      environmental exposure from conception onwards, was introduced in 2005. Since the
      2010s several epidemiological studies, such as the Human Early-Life Exposome
      project, have applied the exposome concept. The exposome consists of three
      overlapping domains: the general external, the specific external, and the
      internal environments. General external factors include the broader socioeconomic
      environment, and specific external factors include lifestyles, occupations, and
      pollutant exposures. Internal factors include biological effects and responses.
      Because the exposome covers exposures from conception to death, the birth cohort
      is an important part of the exposome study. Although there is not yet an
      established consensus in selecting what, when, and where to measure concerning
      the exposome, the use of omics analyses, especially analysis of the metabolome,
      should be considered in order to implement the exposome concept in the birth
      cohort. The exposome needs to be measured repeatedly in certain important phases
      of life, such as during pregnancy and infancy. To perform exposome-informed
      epidemiological studies, untargeted data-driven approaches in conjunction with
      dimension reduction techniques need to be developed and refined. The exposome
      concept has the potential to make a breakthrough in overcoming some of the
      limitations of conventional epidemiology. Concerted national and international
      efforts are required for future exposome studies.

PMID- 28494539
TI  - [Current status and perspectives of diagnosis and treatment of complications
      related to liver cirrhosis].
AB  - Liver cirrhosis is the severe period of chronic liver diseases, especially
      decompensated liver cirrhosis and its complications, such as ascites,
      esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury,
      and hepatocellular carcinoma, which greatly affect patients' quality of life and
      even threaten their lives. Early prevention and treatment of the causes of
      development and progression and pathogenic mechanism may slow down or reverse
      liver cirrhosis and its severe complications. Once the disease progresses to
      portal hypertension and related complications, it is very important to select
      preventive measures for acute exacerbation of different complications, as well as
      the methods and timing for treatment in acute stage, which may help to save
      patients' lives and improve their prognosis.

PMID- 28494540
TI  - [Research advances in pathophysiology and diagnosis and treatment of hepatorenal
      syndrome].
AB  - Hepatorenal syndrome (HRS) is functional renal injury in patients with liver
      cirrhosis or fulminant liver failure and is one of the complications of
      progressive liver failure which threatens patients' lives. With the progression
      of liver diseases, hemodynamic disturbance may eventually cause HRS. Achievements
      have been made in the pathophysiology, diagnostic criteria, and treatment of HRS.
      This article introduces the research advances in the pathophysiology, diagnosis,
      and treatment of HRS.

PMID- 28494541
TI  - [New therapeutic paradigm and concepts for patients with cirrhotic refractory
      ascites].
AB  - The activation of renin-angiotensin-aldosterone-vasopressin system is a key
      factor in the formation of ascites due to splanchnic vasodilation in cirrhosis.
      In theory, aldosterone antagonists, contraction of blood vessels, vasopressin V2
      receptor, and angiotensin receptor antagonists are important targets for the
      prevention and treatment of cirrhotic ascites. The 15%-20% of patients with
      cirrhotic ascites that show no response to at least one week's treatment with
      potent diuretics (spironolactone 160 mg/d combined with furosemide 80 mg/d) are
      considered to have refractory ascites. At present, effective treatments for
      refractory ascites include tolvaptan, large-volume paracentesis (4000-6000
      ml/time/day) combined with albumin (4 g/L ascites), ascites ultrafiltration and
      reinfusion, transjugular intrahepatic portosystemic shunt, and liver
      transplantation. In the future, with the development of vasoactive drugs,
      rifaximin, ascites drainage pump, and other new therapies, the treatment of
      refractory ascites may be more effective to reduce the need for liver
      transplantation.

PMID- 28494542
TI  - [Management algorithm for interrupting mother-to-child transmission of hepatitis
      B].

PMID- 28494543
TI  - [Effects of Anluohuaxianwan on transforming growth factor-beta1 and related
      signaling pathways in rats with carbon tetrachloride-induced liver fibrosis].
AB  - Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used
      to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection.
      However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This
      study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to
      explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven
      male Wistar rats were randomly assigned to control group, model group, and
      treatment group (n = 9 per group). Rats in the model and treatment group were
      injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control
      group were administered saline twice a week for 6 weeks. Starting at week 4
      following model construction, rats in the treatment group received daily gavages
      with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control
      and model groups were given saline for a total of 6 weeks. Alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from
      blood samples collected at the end of weeks 3, 6 and 9. Histopathological
      examination of liver tissue was performed to evaluate liver fibrosis at week 9.
      At the same time, the mRNA expression of TGF-beta1 and Smads in liver tissues was
      quantified by real-time reverse transcription polymerase chain reaction (RT-PCR),
      and TGF-beta1 protein level in the liver was measured by Western blot. Inter
      group comparison was performed using analysis of variance (ANOVA) when the
      continuous data were normally distributed and satisfied the homogeneity of
      variance; otherwise, nonparametric tests were used. Categorical data were
      compared between groups using nonparametric tests. Results: ALHXW markedly
      alleviated liver injury in the treatment group after 3 weeks of therapy as
      indicated by a significantly reduced level of ALT compared with the model group
      [(162.98 +/- 73.14)U/L vs (322.52 +/- 131.76)U/L, P = 0.047], and a 39.8%
      reduction in AST level compared with the model group[ (537.56 +/- 306.06)U/L vs
      (892.98 +/- 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy,
      histopathological diagnosis showed that liver fibrosis was significantly reduced
      in the ALHXW-treated group compared with that in the model group (P = 0.002). The
      relative expression of TGF-beta1 mRNA and protein in the liver were significantly
      lower in ALHXW-treated rats than that in model rats (1.34 +/- 0.31 vs 1.78 +/-
      0.45, P = 0.025; 0.39 +/- 0.02 vs 0.57 +/- 0.04, P = 0.003). Conclusion: ALHXW
      treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of
      anti-fibrosis may occur through the inhibition of TGF-beta1 synthesis and TGF
      beta1/Smads signaling pathway, which in turn suppress the activation of hepatic
      stellate cells and thereby reverses fibrosis.

PMID- 28494544
TI  - [Association between high expression of intrahepatic programmed death-1 and liver
      inflammation in patients with autoimmune hepatitis].
AB  - Objective: To investigate the expression of programmed death-1 (PD-1) in liver
      tissue and its association with liver pathology in patients with autoimmune
      hepatitis (AIH). Methods: A total of 54 AIH patients (38 in the active stage and
      16 in the remission stage) were enrolled, and 9 healthy volunteers were enrolled
      as control group. Immunohistochemistry combined with quantitative image analysis
      was used to measure the expression of PD-1 in liver tissue. The t-test, rank sum
      test, one-way analysis of variance, least significant difference t-test, Mann
      Whitney U test, and Pearson relation analysis were used for statistical analysis
      of different types of data. Results: The AIH group had a significantly higher
      positive rate of PD-1 in liver tissue than the control group (13.57%+/-6.84% vs
      2.22%+/-0.66%, P < 0.01), and the patients in the active stage of AIH had a
      significantly higher positive rate of PD-1 in liver tissue than those in the
      remission stage (16.53%+/-7.72% vs 6.56%+/-3.16%, P < 0.01). The positive rate of
      PD-1 in liver tissue was 6.56%+/-3.16% in G0 group, 14.33%+/-5.08% in G1-2 group,
      and 19.23%+/-5.41% in G3-4 group (P < 0.01), but there was no significant
      difference in the positive rate of PD-1 between S0, S1-2, and S3-4 groups (P >
      0.05). In AIH patients, the positive rate of PD-1 in liver tissue was positively
      correlated with the levels of total bilirubin, alanine aminotransferase,
      aspartate aminotransferase, and IgG (r = 0.665, 0.721, 0.711, and 0.813, all P <
      0.01). Conclusion: AIH patients have regulated PD-1 expression in liver tissue,
      which is closely associated with liver inflammation and is not associated with
      fibrosis degree, suggesting that PD-1 is involved in the development and
      progression of inflammation in AIH patients.

PMID- 28494545
TI  - [Regulatory effect of faciogenital dysplasia 6 gene on hepatic stem cell
      differentiation].
AB  - Objective: To investigate the regulatory effect of faciogenital dysplasia 6
      (FGD6) gene on hepatic stem cell differentiation. Methods: FGD6 gene was selected
      for the co-intervention of target sequence, the AdEasy system was used for the
      construction of adenovirus vector and the packaging and multiplication of the
      recombinant adenovirus vector pSES-FGD6-siRNA, and the HP14.5 cells were
      infected. Immunofluorescence assay was used to measure the expression of FGD6
      protein in HP14.5 cells, quantitative real-time PCR was used to measure the mRNA
      expression of FGD6, alpha-fetoprotein (AFP), and albumin (Alb), and Western blot
      was used to measure the protein expression of FGD6, AFP, and Alb. The empty pSES
      Ad-RFP adenovirus vector was constructed as control in each group. All data were
      expressed as x+/-s, and a one-way analysis of variance was performed. Results:
      FGD6 protein was mainly expressed in the nucleus of HP14.5 cells. The pSES-FGD6
      siRNA adenovirus vector was successfully constructed and it downregulated the
      expression of FGD6 gene and the mRNA and protein expression of AFP in HP14.5
      cells and upregulated the mRNA and protein expression of Alb (P < 0.01).
      Conclusion: The inhibition of the expression of FGD6 gene in HP14.5 cells may
      differentiate HP14.5 cells into hepatocytes. Therefore, FGD6 gene plays an
      important role in the differentiation regulation of hepatic stem cells.

PMID- 28494546
TI  - [Regulatory effect of bone marrow mesenchymal stem cells on polarization of
      macrophages].
AB  - Objective: To examine the regulatory effect of bone marrow mesenchymal stem cells
      (BM-MSCs) on the polarization of bone marrow-derived macrophages, and to provide
      a theoretical support for the application of mesenchymal stem cells in the
      treatment of liver fibrosis. Methods: MSCs and macrophages were first isolated
      from the bone marrow of mice. Macrophages were polarized to M1 macrophages with
      lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), and to M2 macrophages
      with interleukin-4 (IL-4). The macrophages were then co-cultured with BM-MSCs in
      a Transwell for 24 h, and changes in the percentages of M1 and M2 macrophages
      were examined using flow cytometry. The mRNA levels of the M1 macrophage
      associated cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-23a
      (IL-23a), and M2 macrophage-associated molecules, arginase-1 (Arg-1) and CD163,
      were measured by real-time quantitative PCR. The two samples were compared using
      the t test, and P < 0.05 was considered as statistically significant. Results:
      Flow cytometry showed that the percentage of M1 macrophages was significantly
      lower in the (macrophage + LPS + IFN-gamma + BM-MSC) co-culture group than in the
      (macrophage + LPS + IFN-gamma) group (62.5% +/- 4.6% vs 86.6% +/- 6.9%, t =
      5.034, P = 0.0073). In addition, the relative mRNA expression of TNF-alpha and IL
      23a was also significantly reduced in the co-culture group compared with those in
      the macrophage control group as measured by RT-qPCR (t = 11.57 and 10.57,
      respectively, P < 0.05). Compared with that in the macrophage control group, the
      percentage of M2 macrophages in the (macrophage+BM-MSC) co-culture group was
      significantly increased (89.5% +/- 5.8% vs 70.1% +/- 6.3%, t = 3.924, P =
      0.0172), along with significantly elevated relative mRNA expression of Arg1
      (14.35+/-1.05 vs 1.00+/-0.03, t = 21.96, P < 0.05) and CD163 (3.04 +/- 0.27 vs
      1.00 +/- 0.03, t = 13.14, P < 0.05). Conclusion: BM-MSCs can inhibit LPS + IFN
      gamma-induced polarization to M1 macrophages and promote polarization to M2
      macrophages through the release of paracrine factors.

PMID- 28494547
TI  - [Dynamic expression of carnitine palmitoyltransferase II in the mitochondrial
      inner membrane during hepatocyte malignant transformation induced by lipid
      accumulation].
AB  - Objective: To investigate the dynamic expression of hepatic carnitine
      palmitoyltransferase-II (CPT-II) in the mitochondrial inner membrane during
      hepatocyte malignant transformation induced by lipid accumulation. Methods: Male
      Sprague-Dawley rats were divided randomly into control, fatty liver, and induced
      cancer groups, which were fed with normal, high-fat (HF), and HF containing 2
      fluorenylacetamide (0.05%, 2-FAA) diets, respectively, for 14 weeks. One rat from
      each group was sacrificed every two weeks and the blood and liver samples were
      collected. Liver morphological changes were evaluated with hematoxylin and eosin
      staining, and the liver tissue samples were divided into control, fatty liver,
      degeneration, precancerous, and cancerous groups accordingly. Hepatic lipids were
      dyed by the oil red O method. The CPT-II expression was measured by
      immunohistochemistry and compared with the specific CPT-II concentration (ng/mg
      liver protein, ng/mg P) among different groups. Serum levels of circulating total
      cholesterol (Tch), triglyceride (TG), alanine aminotransferase (ALT), and
      aspartate aminotransferase (AST) were quantitatively analyzed. Results: Massive
      lipid accumulation hepatocytes was seen in rats on HF and HF containing 2-FAA
      diets. The lipid levels in the control group were significantly lower than those
      in the fatty liver (t = -11.556, P < 0.001), degeneration (t = -4.847, P = 0.04),
      precancerous (t = -13.652, P = 0.005), and cancerous groups (t = -10.896, P =
      0.008). The serum TG and Tch levels in the degeneration, precancerous, and
      cancerous groups were 2-3 times higher than those in the control group (P <
      0.05). After 2-FAA treatment, the morphological changes of rat hepatocytes showed
      the progression from degeneration and precancerosis to cancerosis, with
      hepatocyte injury. The serum AST and ALT levels in the degeneration,
      precancerous, and cancerous groups were significantly higher (4-8 times) than
      those in the control group (P < 0.05). The specific concentration of liver CPT-II
      expression was significantly reduced during hepatocyte malignant transformation,
      as confirmed by immunohistochemistry, with the CPT-II levels significantly lower
      in the cancerous group than in any of other groups (P < 0.05). Conclusion: Low
      hepatic CPT-II expression might lead to abnormal lipid accumulation in
      hepatocytes, which should promote the malignant transformation of hepatocytes.

PMID- 28494548
TI  - [The role of cytochrome P450 in nonalcoholic fatty liver induced by high-fat
      diet: a gene expression profile analysis].
AB  - Objective: To clarify the role of cytochrome P450 in nonalcoholic fatty liver
      disease (NAFLD) by RNA-Seq and bioinformatics analysis. Methods: A total of 20
      male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60%
      kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice
      were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end
      of the experiment, the body weight, liver weight, and hepatic triglyceride (TG)
      content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed
      for the liver tissues. The differentially expressed genes were screened out and
      subjected to bioinformatics analysis, including KEGG and GO BP enrichment
      analyses and interaction network analysis. Comparison of means between the two
      groups was made using t-test. Results: Compared with the control group, the mice
      in the model group were obviously obese, with significantly increased body weight
      (41.41 +/- 6.01 g vs 28.78 +/- 1.79 g, t = 6.04, P < 0.01) and liver weight (1.38
      +/- 0.30 g vs 1.08 +/- 0.10 g, t = 2.89, P < 0.01). The mice in the model group
      showed obvious steatosis, accompanied by a small amount of inflammatory cell
      infiltration, but with no obvious fibrosis, according to the results of HE
      staining. In addition, the hepatic TG content in the model group was
      significantly increased compared with that in the control group (0.64 +/- 0.01
      mg/mg vs 0.29 +/- 0.06 mg/mg, t = 10.11, P = 0.04). Compared with the control
      group, a total of 367 differentially expressed genes, including 211 down
      regulated and 156 up-regulated ones, were identified in the model group according
      to the RNA-seq results. Meanwhile, 19 CYP450 subtypes, accounting for 5% of the
      differentially expressed genes, were identified, and CYP2E1, CYP2C70, CYP3A11,
      CYP3A25, CYP2D26, CYP4A10, CYP17A1, CYP2B10, and CYP2C38 were involved in
      oxidative stress, steroid hormone metabolism, fatty acid metabolism, arachidonic
      acid metabolism, and the PPAR signaling pathway. An interaction network was
      constructed with 30 nodes, and CYP2E1 and CYP2C70 were identified as key nodes.
      RT-PCR validation results showed that the expression changes of CYP450 subtypes
      and lipid metabolism-related genes were consistent with the findings of
      sequencing. Conclusion: The CYP450 family plays a vital role in the pathogenesis
      of fatty liver by regulating lipid metabolism-related pathways, including
      oxidative stress, arachidonic acid metabolism, steroid hormone metabolism , and
      fatty acid metabolism.

PMID- 28494549
TI  - [Changes in the composition of intestinal microbiota in mice with acute liver
      failure induced by D-galactosamine].
AB  - Objective: To investigate the changes in the composition of intestinal microbiota
      in mice with acute liver failure and identify characteristic bacteria, and to
      provide a basis for the diagnosis and treatment of acute liver failure with
      intestinal microbiota disorders. Methods: A total of 30 specific pathogen-free
      male BALB/c mice were used in this study, including 25 mice in the model group
      and 5 mice in the control group. An acute liver failure model was induced by D
      galactosamine. Microbial DNA was extracted from intestinal contents in different
      segments of the lower digestive tract (ileum and colon) and feces and then were
      amplified using PCR. The regions of 16S V3-V4 were subjected to high-throughput
      sequencing, followed by bioinformatics analyses, including OTU hierarchical
      clustering, species annotation, alpha-diversity analysis, and LEfSe (LDA Effect
      Size) analysis. Comparison of continuous data was made using t-test, while
      comparison of categorical data was made using chi2 test. Results: A total of 10
      mice survived in the two groups, with 80% mortality rate in the model group. The
      alpha-diversity analysis revealed increased bacterial diversity and abundance in
      the ileum, increased bacterial diversity and reduced bacterial abundance in the
      colon, and reduced bacterial diversity and insignificantly changed bacterial
      abundance in feces in the model group compared with the control group. Based on
      the optimized classification level, significantly reduced abundance of
      Clostridiaceae (44.95% +/- 19.28% vs 7.51% +/- 16.57%, P = 0.011) in the ileum,
      whereas significantly increased abundance of Rikenellaceae (1.08% +/- 1.01% vs
      4.18% +/- 2.39%, P = 0.028), S24-7 (4.75% +/- 4.87% vs 22.77% +/- 13.05%, P =
      0.020), and F16 (0.24% +/- 0.28% vs 2.18% +/- 1.61%, P = 0.029) in the colon were
      found in model group compared with the control group. The LEfSe analysis
      demonstrated that there were significant differences in Staphylococcaceae and S24
      7 between the two groups, and S24-7 could be defined as the characteristic
      bacteria. Conclusion: Intestinal microbiota disorders, especially the excessive
      growth of microbes in the ileum, are observed in mice with acute liver failure.
      Moreover, acute liver failure may be closely associated with the excessive growth
      of S24-7.

PMID- 28494550
TI  - [Regulatory effect of vitamin D on proliferation and apoptosis of hepatic
      stellate cells].

PMID- 28494551
TI  - [Value of liver transplantation in treatment of angiosarcoma: a report of 2
      cases].

PMID- 28494552
TI  - [Liver cirrhosis with liver hemochromatosis: a case report].

PMID- 28494553
TI  - [Glycogenosis type IX caused by a novel mutation of phosphorylase kinase alpha
      subunit: a family analysis].

PMID- 28494554
TI  - [Minutes of the 26th Conference of the Asian Pacific Association for the Study of
      the Liver].

PMID- 28494555
TI  - [Liver sinusoidal endothelial cells regulate adaptive immune tolerance in the
      liver].
AB  - Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in
      the liver and are involved in immunological surveillance of the liver through the
      expression of various scavenger receptors and pattern recognition receptors.
      However, in case of several physiological states, viral infections, and tumor
      environment, liver sinusoidal endothelial cells maintain immune tolerance in the
      liver through various mechanisms and cause persistent viral infection and tumor
      metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T
      cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial
      cells.

PMID- 28494556
TI  - [Clinical value of health-related quality of life evaluation in community
      patients with hepatitis B].
AB  - Chronic hepatitis B (CHB) is a major infectious disease which threatens people's
      health around the world. Health-related quality of life (HRQoL) has become an
      important index for evaluating the treatment and prognosis of patients with CHB.
      Many studies abroad have shown that the HRQoL of patients with CHB is influenced
      by various factors. Disease severity, clinical symptoms, and low self-efficacy
      are important influencing factors for patients' quality of life. Anti-viral
      therapy, proper physical therapy, or psychological intervention can significantly
      improve the HRQoL of community CHB patients, and HRQoL is even significantly
      improved in patients undergoing liver transplantation one year ago. These studies
      provide valid evidence for antiviral therapy for hepatitis B patients and liver
      transplantation techniques from the psychological level. At present, there still
      lacks studies on HRQoL of CHB patients in China. This article summarizes the
      measurement tools for HRQoL widely used in recent years in China and foreign
      countries, reviews the research advances in HRQoL in community patients with CHB,
      and discusses the perspectives for future studies.

PMID- 28494557
TI  - [Clinicopathologic features of drug-induced vanishing bile duct syndrome].
AB  - Vanishing bile duct syndrome (VBDS) manifests as progressive destruction and
      disappearance of the intrahepatic bile duct caused by various factors and
      cholestasis. VBDS associated with drug-induced liver injury (D-VBDS) is an
      important etiology of VBDS, and immune disorder or immune imbalance may be the
      main pathogenesis. According to its clinical symptoms, serological markers, and
      course of the disease, D-VBDS is classified into major form and minor form, and
      its clinical features are based on various pathomorphological findings. Its
      prognosis is associated various factors including regeneration of bile duct
      cells, number of bile duct injuries, level and range of bile duct injury, bile
      duct proliferation, and compensatory shunt of bile duct branches. This disease
      has various clinical outcomes; most patients have good prognosis after drug
      withdrawal, and some patients may experience cholestatic cirrhosis, liver
      failure, and even death. Due to the clinical manifestation and biochemical
      changes are similar to the primary biliary cholangitis (PBC) and primary
      sclerosing cholangitis (PSC), it need to identify by clinical physician.

PMID- 28494558
TI  - [Complications of minimally invasive vitreous surgery can not be ignored].
AB  - Pars plana vitrectomy (PPV) has become an important means of treating complex
      vitreoretinopathy, and the introduction of small-gauge PPV instrumentation and
      techniques has even considerably widened the surgery choice. Though the small
      gauge PPV systems have many advantages, ophthalmologists must realize that the
      small-gauge PPV does not necessarily refer to minimally invasive PPV.
      Ophthalmologists should not just pursue the small incision, ignore the principle
      of minimally invasive PPV and the rational choice of indications, and
      underestimate surgical risks and postoperative complications. Ophthalmologists
      must be familiar with the advantages and limitations of minimally invasive PPV so
      as to achieve the best therapeutic effects with minimized trauma. (Chin J
      Ophthalmol, 2017, 53: 321-324).

PMID- 28494559
TI  - [Comparative study of the effects of sterilized air and perfluoropropane gas
      tamponades on recovery after idiopathic full-thickness macular hole surgery].
AB  - Objective: To compare the effects of sterilized air and perfluoropropane
      (C(3)F(8)) tamponades on recovery after vitrectomy for the treatment of
      idiopathic full-thickness macular hole (IFTMH). Methods: Case control study.
      Seventy-three eyes of 69 consecutive cases underwent vitrectomy with air (53
      eyes) or 10% C(3)F(8) gas (20 eyes) tamponade. Surgical outcomes were
      retrospectively analyzed between the two groups, including logarithm of the
      minimal angle of resolution (logMAR) and optical coherence tomography findings
      like the size of the macular hole and the photoreceptor layer defect. Results:
      Preoperatively, the mean best corrected visual acuity (BCVA) was (0.10+/-0.49),
      the mean hole diameter was (777.9+/-320.7) MUm, and the mean diameter of the
      photoreceptor layer defect was (1 709.3+/-516.0) MUm in the sterilized air group,
      while in the C(3)F(8) group, the mean BCVA was (0.07+/-0.50), the mean hole
      diameter was (853.9+/-355.0) MUm, and the mean defect diameter was (1 480.5+/
      429.9) MUm. The primary closure rate was 90.6% in the sterilized air group and
      95.0% in the C(3)F(8) group. One month after surgery, the mean BCVA was (0.17+/
      0.41), and the mean diameter of the photoreceptor layer defect was (820.5+/
      598.0) MUm in the sterilized air group, while in the C(3)F(8) group, the mean
      BCVA was 0.12+/-0.49, and the mean defect diameter was (762.5+/-658.0) MUm. There
      was no statistically significant difference in the closure rate (chi(2)=0.019),
      BCVA (t=-1.689), hole diameter (t=0.837) and diameter of the photoreceptor layer
      defect (t=0.338) between the two groups(P>0.05). Conclusions: Vitrectomy with
      sterilized air tamponade is safe and effective for the treatment of IFTMH and
      even cases with relatively large diameters. (Chin J Ophthalmol, 2017, 53: 327
      331).

PMID- 28494560
TI  - [Visual impact of sub-tenon's anesthesia during surgery for retinal detachment].
AB  - Objective: To investigate the visual impact and influence factors of sub-Tenon's
      anesthesia in retinal detachment patients during pars plana vitrectomy (PPV) or
      combined phacoemulsification and PPV surgery. Methods: In this prospective case
      series study, 104 consecutive patients who underwent PPV or combined
      phacoemulsification and PPV under sub-Tenon's anesthesia between October 2012 and
      December 2013 were enrolled. Intraoperatively, the patients were asked whether
      they could see the light of the operating microscope or not at 5 minutes after
      sub-Tenon's anesthesia, and at the end of phacoemulsification, core vitreous
      removal, peripheral vitreous removal and the whole surgery, with their
      contralateral eyes being covered tightly and no photobleaching. The best
      corrected visual acuity and visual evoked potentials were examined and compared
      with each other preoperatively and at 1.5 months and 3 months postoperatively.
      Chi-square test was used to compare the detection rate of amaurosis between
      different modus operandi and whether covered contra-lateral eye. Student-t test
      was used to compare the difference of age and preoperative BCVA between the
      patients with or without experienced amaurois. Lastly, BCVA between different
      times were tested by one-way ANOVA analysis. Results: Without covering the
      contralateral eyes, the incidence of no light perception in various surgical
      steps was 0%, while it was 72.1%(75/104), 93.8%(75/80), 96.2%(100/104),
      96.2%(100/104) and 86.5%(90/104) at the five timepoints, respectively, when the
      contralateral eyes were covered tightly. The incidence was 51.9%(54/104),
      85.0%(68/80), 85. 6%(89/104), 84.6%(69/104) and 66.3%(88/104), respectively,
      after photobleaching was excluded. Approximately 95.2%(99/104) of patients
      reported no light perception at least once, 54.5%(54/99) reported no light
      perception 5 minutes after sub-Tenon's anesthesia, and 30.3%(30/99) recovered
      light perception when the surgery was finished. All eyes recovered to at least
      light perception on the first postoperative day. The best corrected visual acuity
      and visual evoked potentials at 1.5 months and 3 months postoperatively were
      significantly better than those before surgery. The BCVA was 1.75+/-0.78
      preoperative, 0.96+/-0.63 1.5 months after operation, and 0.92+/-0.57 3 months
      after operation. There was a significant statistical difference between
      preoperative BCVA and postoperative BCVA (F=50.61, P<0.01) . In patients without
      waveform detection preoperatively, PVEP waveform could be found in 43.6% and
      61.4% of the pactients at 1.5 months and 3 months after operation respectively.
      In those had certain waveform preoperatively, PVEP amplitudes rise significantly
      after surgery (t(1.5)=-2.69, t(3)=-2.97, P<0.05) . Conclusions: No light
      perception was detected in various surgical steps of vitrectomy under sub-Tenon's
      anesthesia in most patients. The blocking of optic nerve conduction may be caused
      by sub-Tenon' s anesthesia. Photobleaching can also have some effect. The
      incidence of no light perception during the surgery was not correlated with
      preoperative visual acuity, age and gender. Moreover, the effect was transient
      and harmless to visual function.(Chin J Ophthalmol, 2017, 53: 332-337).

PMID- 28494561
TI  - [Observation of single-layered inverted internal limiting membrane flap technique
      for macular hole with retinal detachment in high myopia].
AB  - Objective: To compare the outcome of pars plana vitrectomy (PPV) with a single
      layered inverted internal limiting membrane (ILM) flap versus PPV with ILM
      peeling for the treatment of macular hole associated retinal detachment (MHRD) in
      high myopia. Methods: In a retrospective cohort study, PPV with 2 kinds of
      adjuvant surgical procedures were used in 35 moderately high myopia eyes with
      MHRD. These eyes were divided into 2 groups: group 1 (17 eyes) receiving PPV and
      ILM peeling and group 2 (18 eyes) receiving PPV with a single-layered inverted
      ILM flap. Anatomical reattachment of the retina, macular hole closure, and best
      corrected visual acuity (BCVA) were measured at 6 months after surgery. Results:
      The retina was successfully reattached in all cases. The difference of the
      retinal reattachment rate between the two groups was not statistically
      significant (Fisher's exact test, P=1.000). The rate of macular hole closure was
      47.1% in group 1 (8 eyes) and 88.9% in group 2 (16 eyes). The difference of the
      macular hole closure rate between the two groups was statistically significant
      (Fisher's exact test, P= 0.012). Significant improvement in logarithm of minimal
      angle of resolution (logMAR) BCVA was achieved in both groups. There was no
      difference in the initial, final, or improved logMAR BCVA in the 2 groups.
      Conclusion: Single-layered inverted ILM flap technique effectively helps close
      the macular hole in moderately high myopia with MHRD. This may prevent the
      possible redetachment from the macular hole. (Chin J Ophthalmol, 2017, 53: 338
      343).

PMID- 28494562
TI  - [Intraoperative risk factors associated with visual acuity outcomes of pars plana
      vitrectomy in idiopathic epiretinal membrane].
AB  - Objective: To evaluate intraoperative risk factors related to the postoperative
      visual acuity in idiopathic epiretinal membrane (IERM) . Methods: According to
      the well-established study criterion, a retrospective observational study was
      carried out on 37 eyes of 37 patients with epiretinal membrane peeling surgery
      for IERM between January 2014 and January 2015. Intraoperative situations during
      membrane peeling were documented, including complexity of operation, superficial
      hemorrhage and the state of indocyanine green (ICG) staining. Best-corrected
      visual acuity (BCVA) measurement and optical coherence tomography were performed
      before and 1, 3, 6 and 12 months after surgery. Multifocal electroretinography
      and fundus fluorescein angiography were conducted at 6 months postoperatively.
      The patients were divided into two groups based on the BCVA (>=0.5 and<0.5) at 6
      months after surgery. The BCVA was converted to logarithm of the minimum angle of
      resolution (logMAR) equivalents for statistical analysis. The relationship
      between intraoperative factors and postoperative visual acuity was analyzed by
      multiple logistic regression analysis. Results: All patients completed follow-ups
      in an average duration of (14.41+/-2.33) months. Among the 37 patients, 28
      patients (75.7%) were in the BCVA >=0.5 group. and 9 patients (24.3%) were in the
      BCVA<0.5 group. Statistical analysis revealed that superficial hemorrhage during
      membrane peeling was associated with poor visual acuity after surgery (OR: 7.221,
      95% CI: 1.775-29.372, P=0.006) . The peeling complexity was positively increased
      with presence of superficial hemorrhage (gamma=0.336, P=0.042) and ICG staining
      (gamma=0.593, P=0.000) . The electroretinography revealed that the average
      latency of N1 wave at ring 1 in eyes with superficial hemorrhage (16.88+/-1.27)ms
      was longer than that in eyes without superficial hemorrhage (12.80+/-4.21)ms at 6
      months postoperatively (t=-2.187, P= 0.042). The fluorescein angiography showed 8
      in 10 eyes with superficial hemorrhage had leakage on the macular fovea.
      Conclusions: Superficial hemorrhage in IERM peeling is a risk factor for the poor
      postoperative visual function. Complex peeling contributes to superficial
      hemorrhage and the positive staining of ICG. (Chin J Ophthalmol, 2017, 53:344
      351).

PMID- 28494563
TI  - [The clinical manifestations and imaging characteristics of acute syphilitic
      posterior placoid chorioretinitis].
AB  - Objective: To investigate the clinical manifestations and imaging characteristics
      of acute syphilitic posterior placoid chorioretinitis (ASPPC). Methods:
      Retrospective study of 10 patients diagnosed ASPPC in the Department of
      Ophthalmology, Beijing Tongren Hospital from 2011 to 2016, including 6 males (10
      eyes involved) and 4 females (8 eyes involved) with an age of (43.4+/-11.6) years
      (range, 26-60 years). Their clinical manifestations and imaging characteristics
      were summarized. Results: All 10 ASPPC patients complained about the reduction of
      visual acuity, and the majority of them had both eyes involved. The initial
      visual acuity ranged from finger count to 0.8, with an average of 0.4 and a
      median visual acuity of 0.3. The intraocular pressure was in the normal range.
      The inflammation of anterior chamber occurred in only one patient (1/10). The
      lesions were located at the posterior pole as shown on fundus photographs. There
      are six placoid lesions, four yellowish massive lesions and seven mixed lesions
      (placoid and yellowish massive lesions). Partial or whole disappearance,
      abnormality and opacity of the ellipsoid layer, retinal pigment epithelial (RPE)
      nodules, and cells in the vitreous body were observed by optical coherence
      tomography. There were partial detachment between the neuronal retina and RPE
      layer with fine-sand like hypereflective dots. The lesion size and morphology on
      autofluorescence (AF), fundus fluorescence angiography (FFA) and indocyanine
      green angiography (ICG) were almost consistent with those on fundus photography.
      The lesions were hyperautofluorescent in a placoid or massive shape. The lesions
      on FFA showed slight hyperfluorescence with unclear edges from the venous phase,
      and the fluorescence increased with the time and leaked in the late phase.
      Vascular walls showed blood staining in the late phase. The lesions on ICG showed
      hypofluorescence with hyperfluorescence and hypofluorescence dots like fine
      needles in the middle and late phases. Conclusion: ASPPC mainly occurs among the
      young adults without gender difference. The characteristic is the contradiction
      between sever clinical symptoms and slight signs on the fundus. The lesion area
      shown on fundus photography, FFA, ICG and AF is consistent, as well as injuries
      of the ellipsoid layer, RPE nodules and cells in the vitreous body. The above
      manifestations and imaging characteristics of ASPPC are significant for the
      diagnosis and differential diagnosis. (Chin J Ophthalmol, 2017, 53:352-357).

PMID- 28494564
TI  - [Clinical observation and related factors analysis of neonatal asphyxia
      complicated with retinal hemorrhage].
AB  - Objective: To observe and analyze related factors of neonatal asphyxia
      complicated with retinal hemorrhage. Methods: It was a retrospective case series.
      Seven hundred and twenty-one cases with neonatal asphyxia after 72 hours of birth
      were enrolled in this study. Fundus examination was performed on these newborns
      using the third generation wide-angle digital retina imaging system (RetCamIII),
      and the bleeding level was divided into level I, level II and level III. The
      conditions of the newborn and the mother during pregnancy were correlatively
      analyzed. The other factors were also analyzed including delivery mode, birth
      weight, gestational age, gender, grade of neonatal asphyxia, scalp hematoma,
      intracranial hemorrhage, fetal intrauterine distress, mother's age and antenatal
      complications. Single factor chi(2) test and multivariate logistic regression
      analysis were used to screen and judge risk factors causing retinal hemorrhage
      related to neonatal asphyxia. Results: In 721 cases of neonatal asphyxia, retinal
      hemorrhage was found in 204 newborns (28.29%). The hemorrhage was at level I in
      77 cases (37.75%) , at level II in 38 cases (18.63%) and at level III in 89 cases
      (43.63%) . Four cases also had vitreous hemorrhage. Asphyxia was mild in 673
      infants (93.34%) and severe in 48 infants (6.66%). The difference in the degree
      of retinal hemorrhage between the patients with mild and severe asphyxia was
      significant (chi(2)=22.336, P=0.000). When asphyxia was aggravated, the degree of
      retinal hemorrhage increased. Relative factors analysis showed that delivery mode
      (chi(2)=158.643, P<0.05), gestational age (chi(2)=24.522, P<0.05), birth weight
      (chi(2)=11.916, P<0.05) and grade of neonatal asphyxia (chi(2)=19.809, P<0.05)
      had correlations with retinal hemorrhage. Logistic regression analysis indicated
      that grade of neonatal asphyxia and delivery mode were risk factors of retinal
      hemorrhage in neonatal asphyxia (OR=0.304, 0.085). Conclusion: The incidence of
      retinal hemorrhage in neonatal asphyxia was 28.29%. The degree of neonatal
      asphyxia and delivery mode may play roles in the occurrence of retinal hemorrhage
      in newborns with asphyxia. With aggravation of asphyxia, the degree of retinal
      hemorrhage may increase. (Chin J Ophthalmol, 2017, 53: 358-362).

PMID- 28494565
TI  - [The protection of hydrogen-rich saline on a rat dry eye model induced by
      scopolamine hydrobromide].
AB  - Objective: To evaluate the effect of hydrogen-rich saline (HRS) on dry eye rats
      induced by subcutaneous injection of scopolamine hydrobromide. Methods:
      Experiment research. Thirty female Wistar rats at about six weeks old were
      randomly divided into the normal group, dry eye group, HRS eyedrops group, normal
      saline eyedrops group (NS), HRS intraperitoneal injection group and NS
      intraperitoneal injection group, with 5 rats in each group. The dry eye was
      induced by subcutaneous injection of scopolamine hydrobromide in the latter five
      groups. The clinical signs of dry eye such as tear volume (SIt), tear break-up
      time (BUT) and corneal epithelial fluorescein staining scores were evaluated on
      day 7, 14, 21 and 28. On the 28th day, ten eyes in each group were enucleated and
      processed for paraffin sections for HE, PAS and immunohistochemistry stainings.
      Analysis of variance was used to test the data, and independent samples t-test
      was used for comparison between the two groups. Two-way repeated measure ANOVA
      was used to compare the difference among groups at different time points, one-way
      ANOVA was used to test the comparisons of the clinical signs at one time, and LSD
      was used to for comparison between two groups. Results: Before and after the
      experiment of the day 7, 14, 21, 28, the values of SIt in HRS eyedrops group and
      HRS intraperitoneal injection group were respectively:(3.625+/-1.157),(3.313+/
      0.704),(3.250+/-0.535),(3.313+/-0.372), (3.375+/-0.582)mm and (3.500+/-1.019),
      (2.893+/-0.656), (3.321+/-0.668), (3.179+/-0.575), (3.214+/-0.871)mm. The values
      of BUT were respectively: (2.750+/-0.707), (2.688+/-0.594), (2.813+/-0.753),
      (3.000+/-0.756), (2.750+/-0.707)s and (3.000+/-0.679), (2.321+/-0.464), (2.750+/
      0.753), (3.214+/-0.699), (2.679+/-0.608)s. The values of fluorescein staining
      score were respectively: (6.250+/-0.707), (8.875+/-0.641), (8.750+/-0.707),
      (9.250+/-0.463), (8.250+/-1.282) and (6.000+/-0.679), (9.143+/-1.027), (8.857+/
      0.770), (9.143+/-0.949), (8.500+/-0.760). The difference of SIt, BUT and
      fluorescein staining score between the groups was statistically significant on
      the 14th day(F=5.194, 3.894, 16.487, P<0.05), the values of SIt, BUT and
      fluorescein staining score of HRS eyedrops group showed significantly better than
      NS eyedrops group(P<0.05), HRS intraperitoneal injection group showed
      significantly better than NS intraperitoneal injection group(P<0.05), and there
      was no significant difference between HRS eyedrops group and HRS intraperitoneal
      injection group(P>0.05), which remained stable until the day 28. On the 28(th)
      day, HE, PAS and immunohistochemistry stainings showed the corneal and
      conjunctival epithelia became smooth and regular, the cell layer number
      decreased, the tissue hyperplasia and edema were lightened, and the size of
      goblet cells tended to be normal, and the squamous metaplasia and inflammation
      were relieved. In HRS eyedrops group and HRS intraperitoneal injection group.
      Conclusions: HRS eyedrops group and HRS intraperitoneal injection group can
      relieve the signs of dry eye, improve the pathological damage of cornea and
      conjunctiva, and protect the ocular surface of a rat dry eye model, which is
      better than NS groups from the 14(th) day. (Chin J Ophthalmol, 2017, 53: 363
      372).

PMID- 28494567
TI  - [The advances in research on precisely inducing retinal ganglion cells from stem
      cells].
AB  - The injury and repair of retinal neurons is a common scientific problem in the
      occurrence, development and prognosis of neuronal visual impairment. Transplant
      of retinal ganglion cells (RGCs) differentiated from stem cells opens a new
      avenue for treatment of glaucoma and optic neuronal degenerative diseases. For
      the goal to explore the optimal method for RGCs replacement, this review
      summarizes the current information regarding the classification and application
      of stem cells, the growth characteristics of RGCs and the precise methods to
      induce RGCs, and discusses some important issues that need resolving and are
      related to RGCs transplantation. It is hoped that this article will provide
      useful theoretical basis for the research of this field. (Chin J Ophthalmol,
      2017, 53: 381-385).

PMID- 28494566
TI  - [The prevalence of blindness caused by primary angle closure glaucoma in middle
      aged Chinese population: a systematic review and meta-analysis].
AB  - Objective: To evaluate the rate of blindness caused by primary angle closure
      glaucoma (PACG) in Chinese population of more than 40 years old, and to explore
      the effectiveness of a prevention and treatment system on PACG. Methods: We
      searched the databases of Pubmed, ScienceDirect, Springer Link, CNKI and Wanfang
      Data and collected all the original studies of the prevalence and blindness of
      angle closure glaucoma in China. The population was limited to over 40 years old.
      The research site was limited to the community-based, while the published time
      was not limited. Two researchers completed the literature search, data extraction
      and methodological quality assessment independently, with same criteria. Meta
      analysis was performed using R software. Results: Five papers were included in
      this study finally. A total of 26 437 cases of natural population over the age of
      40 were observed, and 306 cases of angle closure glaucoma were found, of which
      113 cases had binocular or monocular blindness caused by PACG. The random effect
      model meta-analysis results showed that the overall blindness rate was 38.3%
      [95%CI (28.1%, 49.6%)]. In Beijing, where the prevention and treatment system was
      well established, the blindness rate was far lower than that in the areas where
      the system was poorly established. Compared with the past, the blindness rate
      caused by PACG in Beijing decreased sharply. Conclusions: The rate of blindness
      caused by PACG is still high in the mainland of China. The prevention and
      treatment system is effective and worth promoting. (Chin J Ophthalmol, 2017, 53:
      373-377).

PMID- 28494568
TI  - [The research advances and applications of genome editing in hereditary eye
      diseases].
AB  - Genome editing is a cutting-edge technology that generates DNA double strand
      breaks at the specific genomic DNA sequence through nuclease recognition and
      cleavage, and then achieves insertion, replacement, or deletion of the target
      gene via endogenous DNA repair mechanisms, such as non-homologous end joining,
      homology directed repair, and homologous recombination. So far, more than 600
      human hereditary eye diseases and systemic hereditary diseases with ocular
      phenotypes have been found. However, most of these diseases are of incompletely
      elucidated pathogenesis and without effective therapies. Genome editing
      technology can precisely target and alter the genomes of animals, establish
      animal models of the hereditary diseases, and elucidate the relationship between
      the target gene and the disease phenotype, thereby providing a powerful approach
      to studying the pathogenic mechanisms underlying the hereditary eye diseases. In
      addition, correction of gene mutations by the genome editing brings a new hope to
      gene therapy for the hereditary eye diseases. This review introduces the
      molecular characteristics of 4 major enzymes used in the genome editing,
      including homing endonucleases, zinc finger nucleases, transcription activator
      like effector nucleases, and clustered regularly interspaced short palindromic
      repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9), and summarizes the current
      applications of this technology in investigating the pathogenic mechanisms
      underlying the hereditary eye diseases. (Chin J Ophthalmol, 2017, 53: 386-371).

PMID- 28494569
TI  - [Research advances on cortical functional and structural deficits of amblyopia].
AB  - Previous studies have observed functional deficits in primary visual cortex. With
      the development of functional magnetic resonance imaging and electrophysiological
      technique, the research of the striate, extra-striate cortex and higher-order
      cortical deficit underlying amblyopia reaches a new stage. The neural mechanisms
      of amblyopia show that anomalous responses exist throughout the visual processing
      hierarchy, including the functional and structural abnormalities. This review
      aims to summarize the current knowledge about structural and functional deficits
      of brain regions associated with amblyopia. (Chin J Ophthalmol, 2017, 53: 392
      395).

PMID- 28494570
TI  - Investigation of Bulk Traps by Conductance Method in the Deep Depletion Region of
      the Al2O3/GaN MOS Device.
AB  - Conductance method was employed to study the physics of traps (e.g., interface
      and bulk traps) in the Al2O3/GaN MOS devices. By featuring only one single peak
      in the parallel conductance (G p/omega) characteristics in the deep depletion
      region, one single-level bulk trap (E C-0.53 eV) uniformly distributed in GaN
      buffer was identified. While in the subthreshold region, the interface traps with
      continuous energy of E C-0.4~0.57 eV and density of 0.6~1.6 * 1012 cm-2 were
      extracted from the commonly observed multiple G p/omega peaks. This methodology
      can be used to investigate the traps in GaN buffer and facilitates making the
      distinction between bulk and interface traps.

PMID- 28494571
TI  - Synthesis of n-type Mg2Si/CNT Thermoelectric Nanofibers.
AB  - Magnesium silicide (Mg2Si)/carbon nanotube (CNT) thermoelectric nanofibers for
      use as a flexible thermoelectric material were successfully synthesized through
      the combined processes of the sol-gel method, magnesiothermic reduction, and
      liquid-solid phase reaction. In the resulting product, each CNT was coated with
      Mg2Si which was an approximately 60-nm-thick single crystal. The synthesized
      Mg2Si-coated CNTs exhibited n-type thermoelectric behavior confirming that n-type
      thermoelectric composite nanofibers were successfully obtained.

PMID- 28494572
TI  - SERS Detection of Biomolecules by Highly Sensitive and Reproducible Raman
      Enhancing Nanoparticle Array.
AB  - This paper describes the preparation of nanoarrays composed of silver
      nanoparticles (AgNPs: 20-50 nm) for use as surface-enhanced Raman scattering
      (SERS) substrates. The AgNPs were grown on porous anodic aluminum oxide (AAO)
      templates by electrochemical plating, and the inter-channel gap of AAO channels
      is between 10 and 20 nm. The size and interparticle gap of silver particles were
      adjusted in order to achieve optimal SERS signals and characterized by scanning
      electron microscopy, atomic force microscopy, and Raman spectroscopy. The
      fluctuation of SERS intensity is about 10-20% when measuring adenine solutions,
      showing a great reproducible SERS sensing. The nanoparticle arrays offer a large
      potential for practical applications as shown by the SERS-based quantitative
      detection and differentiation of adenine (A), thymine (T), cytosine (C), guanine
      (G), beta-carotene, and malachite green. The respective detection limits are <1
      ppb for adenine and <0.63 ppm for beta-carotene and malachite green,
      respectively. Uniform and reproducible Raman enhancement enabled by Ag
      nanoparticle array embedded in anodic aluminum oxide differentiates and helps
      quantify DNA canonical nucleobases (adenine, thymine, cytosine, and guanine).

PMID- 28494573
TI  - Hysteresis of Low-Temperature Thermal Conductivity and Boson Peak in Glassy (g)
      As2S3: Nanocluster Contribution.
AB  - Experimental results of the thermal conductivity (k(T)) of nanostructured g-As2S3
      during cooling and heating processes within the temperature range from 2.5 to 100
      K have been analysed. The paper has considered thermal conductivity is weakly
      temperature k(T) dependent from 2.5 to 100 K showing a plateau in region from 3.6
      to 10.7 K during both cooling and heating regimes. This paper is the first
      attempt to consider the k(T) hysteresis above plateau while heating in the range
      of temperature from 11 to 60 K. The results obtained have not been reported yet
      in the scientific literature. Differential curve Deltak(T) of k(T) (heating k(T)
      curve minus cooling k(T) curve) possesses a complex asymmetric peak in the energy
      range from 1 to 10 meV. Deltak(T) reproduces the density of states in a
      g(omega)/omega 2 representation estimated from a boson peak experimentally
      obtained by Raman measurement within the range of low and room temperatures.
      Theoretical and experimental spectroscopic studies have confirmed a glassy
      structure of g-As2S3 in cluster approximation. The origin of the low-frequency
      excitations resulted from a rich variety of vibrational properties. The
      nanocluster vibrations can be created by disorder on atomic scale.

PMID- 28494574
TI  - Endoscopic Management of Peri-Pancreatic Fluid Collections.
AB  - In the past decade, there has been a progressive paradigm shift in the management
      of peri-pancreatic fluid collections after acute pancreatitis. Refinements in the
      definitions of fluid collections from the updated Atlanta classification have
      enabled better communication amongst physicians in an effort to formulate optimal
      treatments. Endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts
      has emerged as the procedure of choice over surgical cystogastrostomy. The
      approach provides similar success rates with low complications and better quality
      of life compared with surgery. However, an endoscopic "step up" approach in the
      management of pancreatic walled-off necrosis has also been advocated. Both
      endoscopic and percutaneous drainage routes may be used depending on the
      anatomical location of the collections. New-generation large diameter EUS
      specific stent systems have also recently been described. The device allows
      precise and effective drainage of the collections and permits endoscopic
      necrosectomy through the stents.

PMID- 28494575
TI  - Combination Therapy for Chronic Hepatitis B: Current Updates and Perspectives.
AB  - Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades
      to treat chronic hepatitis B; however, the therapeutic response remains
      unsatisfactory. Although NUC therapy exhibits potent on-treatment viral
      suppression, frequent off-therapy virological relapses suggest an indefinite
      treatment course. Interferon modulates the innate and adaptive antiviral immune
      responses and thus increases the chance of viral eradication. Interferon therapy
      has the advantage of a finite duration, absence of drug resistance, and durable
      posttreatment responses. Therefore, the combination of NUCs and interferon can
      theoretically facilitate a synergistic therapeutic effect. This paper summarizes
      the current strategies of various combination therapies into three categories:
      the simultaneous "dual" strategy, sequential combination "add-on" strategy, and
      "switch" strategy. Generally, dual therapy exhibits greater on-treatment and off
      therapy viral suppression and lower drug resistance compared with NUC
      monotherapy. Compared with interferon monotherapy, dual therapy has greater on
      treatment viral suppression but shows no difference in off-therapy sustained
      virological responses. Specific add-on or switch strategies provide promising on
      treatment efficacy in select patients. Pretreatment or on-treatment quantitative
      hepatitis B surface antigen and e antigen are predictive for the treatment
      efficacy of combination therapy. The optimal schedule of combination regimens and
      individualized therapy remain to be comprehensively evaluated.

PMID- 28494576
TI  - Diverticular Disease: An Update on Pathogenesis and Management.
AB  - Diverticular disease is one of the most common conditions in the Western world
      and one of the most common findings identified at colonoscopy. Recently, there
      has been a significant paradigm shift in our understanding of diverticular
      disease and its management. The pathogenesis of diverticular disease is thought
      to be multifactorial and include both environmental and genetic factors in
      addition to the historically accepted etiology of dietary fiber deficiency.
      Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a
      type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome.
      Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some
      patients with SUDD, although their role(s) in preventing complications remain
      unclear. Antibiotic use for acute diverticulitis and elective prophylactic
      resection surgery are considered more individualized treatment modalities that
      take into account the clinical status, comorbidities and lifestyle of the
      patient. Our understanding of the pathogenesis of diverticular disease continues
      to evolve and is likely to be diverse and multifactorial. Paradigm shifts in
      several areas of the pathogenesis and management of diverticular disease are
      explored in this review.

PMID- 28494578
TI  - Early and late ureteral complications after renal transplant.
AB  - BACKGROUND: Ureteral strictures occur in approximately 3-8% of kidney transplant
      (KTx) recipients. They are usually a late event which needs surgical re
      intervention with a subsequent increased risk of graft loss. This retrospective
      study presents a single-centre experience in managing ureteral complications
      using firstly a minimally invasive approach. METHODS: Between January 2000 and
      November 2012, 838 patients underwent KTx with Lich-Gregoire uretero-vesical
      anastomosis. Ureteral complications consisting in 6 fistulas and 18 strictures
      were observed in 24 grafts, with an overall incidence of 2.6%. The retrograde
      placement of a double J stent was attempted first in 16 grafts and succeeded in
      12 (75%); the remaining 4 cases underwent open repair with anastomosis to the
      native ureter. Antegrade/combined ureteral stenting via a percutaneous
      nephrostomy was attempted in 8 grafts and succeeded in 4 (50%); the remaining 4
      (2 fistulas and 2 strictures) underwent open repair with anastomosis to the
      native ureter. RESULTS: After an average period of 8.36 months (range 1-36) the
      double J stents were removed and the ureters were unobstructed in 11 (45.8%),
      while open surgical treatment was necessary in the remaining 5. Repeated
      cystoscopic stent changes were successfully performed in 13 patients. Early onset
      ureteral stenoses were found in 10 out of 19 patients and successfully treated by
      a mini-invasive approach in 50% of the cases. Three renal grafts were lost, but
      this was not due to ureteral complications. CONCLUSIONS: Minimally invasive
      procedures are recommended in early complications, although open reconstructive
      surgery maintains a role in late severe obstructions after KTx.

PMID- 28494577
TI  - Sessile Serrated Adenomas: How to Detect, Characterize and Resect.
AB  - Serrated polyps are important contributors to the burden of colorectal cancers
      (CRC). These lesions were once considered to have no malignant potential, but
      currently up to 30% of all CRC are recognized to arise from the serrated
      neoplasia pathway. The primary premalignant lesions are sessile serrated
      adenomas/polyps (SSA/Ps), although traditional serrated adenomas are relatively
      uncommon. Compared to conventional adenomas, SSA/Ps are morphologically subtle
      with indistinct borders, may be difficult to detect endoscopically, are more
      prevalent than previously thought, are associated with synchronous and
      metachronous advanced neoplasia, and have a higher risk of incomplete resection.
      Although many lesions remain "dormant," progressive disease is associated with
      the development of dysplasia and more rapid progression to CRC. As a result,
      SSA/Ps are strongly implicated in the development of interval cancers. These
      factors represent unique challenges that require a meticulous approach to their
      management. In this review, we summarize the contemporary literature on the
      characterization, detection and resection of SSA/Ps.

PMID- 28494579
TI  - Multiparametric prostate MRI: technical conduct, standardized report and clinical
      use.
AB  - Multiparametric prostate MRI (mp-MRI) is an emerging imaging modality for
      diagnosis, characterization, staging, and treatment planning of prostate cancer
      (PCa). The technique, results reporting, and its role in clinical practice have
      been the subject of significant development over the last decade. Although mp-MRI
      is not yet routinely used in the diagnostic pathway, almost all urological
      guidelines have emphasized the potential role of mp-MRI in several aspects of PCa
      management. Moreover, new MRI sequences and scanning techniques are currently
      under evaluation to improve the diagnostic accuracy of mp-MRI. This review
      presents an overview of mp-MRI, summarizing the technical applications, the
      standardized reporting systems used, and their current roles in various stages of
      PCa management. Finally, this critical review also reports the main limitations
      and future perspectives of the technique.

PMID- 28494580
TI  - Access to Chiral Silicon Centers for Application to Circularly Polarized
      Luminescence Materials.
AB  - Asymmetric arylation of secondary silanes catalyzed by a Pd-chiral
      phosphoramidite complex was developed for application to low-molecular-weight
      circularly polarized luminescence (CPL) materials. The asymmetric arylation
      provided a convenient, efficient synthetic method for a variety of chiral
      tertiary silanes (2-21), which were key intermediates for preparing the
      quaternary silicon center. A stepwise, one-pot procedure was used to transform
      the appropriate aryl iodide to the quaternary silane (22) with good yield and
      enantioselectivity. Among compounds synthesized in this work, four optically pure
      tertiary silanes (18-21) were selected to investigate the relationship between
      the structure and optical properties. Optically pure (S,S)-21 displayed the
      highest CPL emission with a high fluorescence quantum yield (glum: +0.008, PhiF:
      0.42). This simple molecular design provides new strategies for developing small
      organic CPL dyes.

PMID- 28494581
TI  - Synthesis of 5-Amino and 3,5-Diamino Substituted 1,2,4-Thiadiazoles by I2
      Mediated Oxidative N-S Bond Formation.
AB  - An oxidative N-S bond formation reaction has been established for 1,2,4
      thiadiazole synthesis employing molecular iodine as the sole oxidant. The
      features of the present reaction include no use of transition metals, mild
      reaction conditions, simple operation, and short reaction time. This versatile
      synthetic approach is broadly applicable to a variety of imidoyl and guanyl
      thiourea substrates to produce 5-amino and 3,5-diamino substituted 1,2,4
      thiadiazole derivatives, respectively, in an efficient and scalable fashion.

PMID- 28494583
TI  - Isolation, Identification, and Biological Evaluation of Phenolic Compounds from a
      Traditional North American Confectionery, Maple Sugar.
AB  - Maple sap, collected from the sugar maple (Acer saccharum) tree, is boiled to
      produce the popular plant-derived sweetener, maple syrup, which can then be
      further evaporated to yield a traditional North American confectionery, maple
      sugar. Although maple sap and maple syrup have been previously studied, the
      phytochemical constituents of maple sugar are unknown. Herein, 30 phenolic
      compounds, 1-30, primarily lignans, were isolated and identified (by HRESIMS and
      NMR) from maple sugar. The isolates included the phenylpropanoid-based lignan
      tetramers (erythro,erythro)-4",4'''-dihydroxy-3,3',3",3''',5,5'-hexamethoxy
      7,9';7',9-diepoxy-4,8";4',8'''-bisoxy-8,8'-dineolignan-7",7''',9",9'''-tetraol,
      29, and (threo,erythro)-4",4'''-dihydroxy-3,3',3",3''',5,5'-hexamethoxy-7,9';7',9
      diepoxy-4,8";4',8'''-bisoxy-8,8'-dineolignan-7",7''',9",9'''-tetraol, 30, neither
      of which have been identified from maple sap or maple syrup before. Twenty of the
      isolates (selected on the basis of sample quantity available) were evaluated for
      their potential biological effects against lipopolysaccharide-induced
      inflammation in BV-2 microglia in vitro and juglone-induced oxidative stress in
      Caenorhabditis elegans in vivo. The current study increases scientific knowledge
      of possible bioactive compounds present in maple-derived foods including maple
      sugar.

PMID- 28494582
TI  - Highly Oxygenated Grayanane Diterpenoids from Flowers of Pieris japonica and
      Structure-Activity Relationships of Antifeedant Activity against Pieris
      brassicae.
AB  - Six new highly oxygenated grayanane diterpenoids, neopierisoids G-L, 1-6,
      together with 10 known related compounds, 7-16, were identified from the flowers
      of the poisonous plant Pieris japonica. The structures were elucidated on the
      basis of comprehensive NMR spectroscopy and mass analysis. The relative
      configurations of 1-6 were elucidated by analysis of ROESY spectra and comparison
      of NMR data with the analogues. The absolute configurations of 1-6 were
      established by the X-ray diffraction analysis of 1 and comparison of the CD
      spectra of 1-6. Compared with the skeleton of the normal grayanane diterpenoids,
      compounds 1-6 shared an unusual seco A ring moiety. The antifeedant activities of
      compounds 1-16 against Pieris brassicae were evaluated by using a dual-choice
      bioassay, and compounds 1-10 with a normal grayanane skeleton showed potent
      antifeedant activity against P. brassicae. The structure-activity relationships
      of antifeedant activities of 1-16 against P. brassicae are discussed.

PMID- 28494584
TI  - Development of a Common Procedure for the Determination of Methylmercury,
      Ethylmercury, and Inorganic Mercury in Human Whole Blood, Hair, and Urine by
      Triple Spike Species-Specific Isotope Dilution Mass Spectrometry.
AB  - We report the first common methodology for the simultaneous determination of
      methylmercury (MeHg), ethylmercury (EtHg), and inorganic mercury (Hg(II)) in
      human blood hair and urine. With the exception of the initial sample mass (0.15 g
      for blood, 0.5 g for urine, and 0.1 g for hair), the same sample preparation and
      gas chromatography-inductively coupled plasma mass spectrometry (GC-ICPMS)
      measurement conditions are employed for the three matrixes providing experimental
      values in agreement with the certified values in the analysis of NIST SRM 955c
      (Caprine Blood) Level 3 and the certified human hairs IAEA 085 and IAEA 086.
      Also, the method provides quantitative recoveries for the three Hg species in the
      analysis of fortified human urine samples at 1, 2, and 5 ng Hg g-1. Mercury
      species concentrations for levels 2 and 4 of SRM 955c are reported here for the
      first time. A systematic interconversion of EtHg into Hg(II) was obtained for all
      matrixes reaching values up to 95% in blood, 29% in hair, and 11% in urine. MeHg
      dealkylation was also observed in a lesser extent in blood and hair analyses, but
      it was not observed when analyzing urine samples. Hg methylation was not observed
      in any matrix. The amount of NaBPr4 added for derivatization has been found to be
      the main factor responsible for Hg species interconversion. This work
      demonstrates for the first time that experimental conditions optimized for SRM
      955c (caprine blood) are not valid for human blood samples as the optimum initial
      sample amount for a real sample is more than 3 times lower than that for SRM
      955c.

PMID- 28494585
TI  - Induced Fit Is a Special Case of Conformational Selection.
AB  - Conformational selection (CS) and induced fit (IF) are two widely used
      interpretations of binding of a ligand to biological macromolecules. Both
      mechanisms envision a two-step reaction in which a conformational transition
      either precedes (CS) or follows (IF) the binding step. Under pseudo-first-order
      conditions where the ligand is in excess compared to the macromolecule, both
      mechanisms produce two relaxations. A fast one eventually increases linearly with
      ligand concentration and reflects the binding interaction. A slow one saturates
      to a constant value after decreasing or increasing hyperbolically with ligand
      concentration. This relaxation is the one most often accessible to experimental
      measurements and is potentially diagnostic of the mechanism involved. A
      relaxation that decreases unequivocally identifies CS, but a hyperbolic increase
      is compatible with both CS and IF. The potential ambiguity between the two
      mechanisms is more than qualitative. Here we show that the entire kinetic
      repertoire of IF is nothing but a mathematical special case of CS as revealed by
      a simple transformation of the rate constants, which emphasizes the need for
      independent support of either mechanism from additional experimental evidence. We
      discuss a simple strategy for distinguishing between IF and CS under the most
      common conditions encountered in practice, i.e., when the ligand is in excess
      compared to the macromolecule and a single relaxation is accessible to
      experimental measurements.

PMID- 28494586
TI  - Thermodynamic Study of the Interaction of Bovine Serum Albumin and Amino Acids
      with Cellulose Nanocrystals.
AB  - The interaction of bovine serum albumin (BSA) with sulfated, carboxylated, and
      pyridinium-grafted cellulose nanocrystals (CNCs) was studied as a function of the
      degree of substitution by determining the adsorption isotherm and by directly
      measuring the thermodynamics of interaction. The adsorption of BSA onto
      positively charged pyridinium-grafted cellulose nanocrystals followed Langmuirian
      adsorption with the maximum amount of adsorbed protein increasing linearly with
      increasing degree of substitution. The binding mechanism between the positively
      charged pyridinum-grafted cellulose nanocrystals and BSA was found to be
      endothermic and based on charge neutralization. A positive entropy of adsorption
      associated with an increase of the degree of disorder upon addition of BSA
      compensated for the unfavorable endothermic enthalpy and enabled formation of
      pyridinium-g-CNC-BSA complexes. The endothermic enthalpy of adsorption was
      further found to decrease as a function of increasing degree of substitution.
      Negatively charged cellulose nanocrystals bearing sulfate and/or carboxylic
      functionalities were found to not interact significantly with the BSA protein. To
      investigate in more detail the role of single amino acids in the adsorption of
      proteins onto cellulose nanocrystals, we also studied the interaction of
      different types of amino acids with CNCs, i.e., charged (lysine, aspartic acid),
      aromatic (tryptophan, tyrosine), and polar (serine) amino acids. We found that
      none of the single amino acids bound with CNCs irrespective of surface charge and
      that therefore the binding of proteins with CNCs appears to require larger amino
      acid sequences that induce a greater entropic contribution to stabilize binding.
      Single amino acids are thus not adsorbed onto cellulose nanocrystals.

PMID- 28494587
TI  - Fabrication and Electrochemical Performance of Structured Mesoscale Open Shell
      V2O5 Networks.
AB  - Crystalline vanadium pentoxide (V2O5) has attracted significant interest as a
      potential cathode material for energy storage applications due to its high
      theoretical capacity. Unfortunately, the material suffers from low conductivity
      as well as slow lithium ion diffusion, both of which affect how fast the
      electrode can be charged/discharged and how many times it can be cycled.
      Colloidal crystal templating (CCT) provides a simple approach to create well
      organized 3-D nanostructures of materials, resulting in a significant increase in
      surface area that can lead to marked improvements in electrochemical performance.
      Here, a single layer of open shell V2O5 architectures ca. 1 MUm in height with
      ca. 100 nm wall thickness was fabricated using CCT, and the electrochemical
      properties of these assemblies were evaluated. A decrease in polarization
      effects, resulting from the higher surface area mesostructured features, was
      found to produce significantly enhanced electrochemical performance. The
      discharge capacity of an unpatterned thin film of V2O5 (~8.1 MUAh/cm2) was found
      to increase to ~10.2 MUAh/cm2 when the material was patterned by CCT, affording
      enhanced charge storage capabilities as well as a decrease in the irreversible
      degradation during charge-discharge cycling. This work demonstrates the
      importance of creating mesoscale electrode surfaces for improving the performance
      of energy storage devices and provides fundamental understanding of the means to
      improve device performance.

PMID- 28494588
TI  - Cyclization of Methyl-Coumalate-Derived Methyl 1-Benzamido-6-oxo-1,6
      dihydropyridine-3-carboxylates: Assembly of the [1,2,4]Triazolo[1,5-a]pyridine
      Ring System.
AB  - An efficient three-step synthesis of a series of fused bicyclic s
      [1,2,4]triazolo[1,5-a]pyridines 1 was accomplished utilizing novel intermediates
      derived from inexpensive, commercially available hydrazides A and methyl
      coumalate B. A significant feature of this approach was the formation of a
      dihydrazide intermediate 2, bypassing the need for oxidative N-N bond formation
      in the 1,2,4-triazole synthesis. Further purification of the dihydrazides 2,
      beyond simple isolation, proved to be unnecessary owing to the impurity rejection
      afforded by the crystalline oxadiazolium salts 3. Additionally, the prepared
      oxadiazolium perchlorate salts showed excellent moisture stability, an unusual
      feature in compounds of this type.

PMID- 28494589
TI  - Complexes Covered with Phosphorylcholine Groups Prepared by Mixing Anionic
      Diblock Copolymers and Cationic Surfactants.
AB  - Anionic diblock copolymers (PmAn) composed of biocompatible polybetaine, poly(2
      (methacryloyloxy)ethyl phosphorylcholine) (PMPC), and anionic poly(sodium 2
      (acrylamido)-2-methylpropanesulfonate) (PAMPS) were synthesized via reversible
      addition-fragmentation chain transfer (RAFT) radical polymerization. Two types of
      diblock copolymers (P24A217 and P100A99) were prepared with different
      compositions. The PmAn/CTAB complexes were formed by a stoichiometrically charge
      neutralized mixture of anionic PmAn and cationic cetyltrimethylammonium bromide
      (CTAB) micelles in water. The complexes prepared using P24A217 and P100A99 were
      vesicles and micelles, respectively, and were covered with hydrophilic PMPC
      shells. The complexes dissociated upon addition of NaCl because the complex was
      maintained through electrostatic interactions. The P24A217/CTAB vesicles could
      encapsulate uncharged hydrophilic guest molecules into the interior of the
      aqueous phase.

PMID- 28494590
TI  - Linking Silica Support Morphology to the Dynamics of Aminopolymers in Composites.
AB  - A combined computational and experimental approach is used to elucidate the
      effect of silica support morphology on polymer dynamics and CO2 adsorption
      capacities in aminopolymer/silica composites. Simulations are based on coarse
      grained molecular dynamics simulations of aminopolymer composites where a
      branched aminopolymer, representing poly(ethylenimine) (PEI), is impregnated into
      different silica mesoporous supports. The morphology of the mesoporous supports
      varies from hexagonally packed cylindrical pores representing SBA-15, double
      gyroids representing KIT-6 and MCM-48, and cagelike structures representing SBA
      16. In parallel, composites of PEI and the silica supports SBA-15, KIT-6, MCM-48,
      and SBA-16 are synthesized and characterized, including measuring their CO2
      uptake. Simulations predict that a 3D pore morphology, such as those of KIT-6,
      MCM-48, and SBA-16, will have faster segmental mobility and have lower
      probability of primary amine and surface silanol associations, which should
      translate to higher CO2 uptake in comparison to a 2D pore morphology such as that
      of SBA-15. Indeed, it is found that KIT-6 has higher CO2 uptake than SBA-15 at
      equivalent PEI loading, even though both supports have similar surface area and
      pore volume. However, this is not the case for the MCM-48 support, which has
      smaller pores, and SBA-16, whose pore structure rapidly degrades after PEI
      impregnation.

PMID- 28494591
TI  - In Situ Multimodal 3D Chemical Imaging of a Hierarchically Structured Core@Shell
      Catalyst.
AB  - A Cu/ZnO/Al2O3@ZSM-5 core@shell catalyst active for one-step conversion of
      synthesis gas to dimethyl ether (DME) was imaged simultaneously and in situ using
      synchrotron-based micro X-ray fluorescence (MU-XRF), X-ray diffraction (MU-XRD),
      and scanning transmission X-ray microscopy (STXM) computed tomography (CT) with
      micrometer spatial resolution. An identical sample volume was imaged stepwise,
      first under oxidizing and reducing atmospheres (imitating calcination and
      activation processes), and then under model reaction conditions for DME synthesis
      (H2:CO:CO2 ratio of 16:8:1, up to 250  degrees C). The multimodal imaging methods
      offered insights into the active metal structure and speciation within the
      catalyst, and allowed imaging of both the catalyst core and zeolite shell in a
      single acquisition. Dispersion of nanosized Cu species was observed in the
      catalyst core during reduction, with formation of a metastable Cu+ phase at the
      core-shell interface. Under DME reaction conditions at 1 bar, the coexistence of
      Cu0 in the active catalyst core together with partially oxidized Cu species was
      unraveled. The zeolite shell and core-shell interface remained stable under all
      conditions, preserving the bifunctional nature of the catalyst. These
      observations are inaccessible using standard bulk techniques like X-ray
      absorption spectroscopy (XAS) and XRD, demonstrating the potential of multimodal
      in situ X-ray CT for characterization of hierarchically designed materials, which
      stand to benefit tremendously from such 3D spatially resolved measurements.

PMID- 28494592
TI  - ACS Infectious Diseases Special Issue Focused on Drug Discovery for Global
      Health.

PMID- 28494593
TI  - Laser irradiation of Mg-Al-Zn alloy: Reduced electrochemical kinetics and
      enhanced performance in simulated body fluid.
AB  - As a lightweight metal with mechanical properties similar to natural bone, Mg and
      its alloys are great prospects for biodegradable, load bearing implants. However,
      rapid degradation and H2 gas production in physiological media has prevented
      widespread use of Mg alloys. Surface heterogeneities in the form of intermetallic
      particles dominate the corrosion response. This research shows that surface
      homogenization significantly improved the biological corrosion response observed
      during immersion in simulated body fluid (SBF). The laser processed Mg alloy
      exhibited a 50% reduction in mass loss and H2 evolution after 24 h of immersion
      in SBF when compared to the wrought, cast alloy. The laser processed samples
      exhibited increased wettability as evident from wetting angle studies, further
      suggesting improved biocompatibility. Electrochemical analysis by potentiodynamic
      polarization measurements showed that the anodic and cathodic kinetics were
      reduced following laser processing and are attributed to the surface chemical
      homogeneity.

PMID- 28494594
TI  - Caring for baby's teeth starts before birth.
AB  - Care for a child's teeth and gums can start even before the baby is born.
      Pregnancy causes many hormonal changes, among these the rise of estrogen and
      progesterone increases the risk of developing oral health problems, like
      gingivitis and periodontitis.The presence of maternal periodontal diseases and
      active infections has been associated with adverse pregnancy outcomes, such as
      preterm birth, preeclampsia, gestational diabetes and foetal loss. Therefore, it
      is important to educate pregnant women about their oral hygiene and the
      importance of taking care of their newborn's oral health. J. Courtad and A.
      Horowitz devised six steps to help us in promoting oral health (ADA Convention-
      2016 Denver): 1. Asking right questions such as "Has there been any change in
      your health history since your last visit?" and "When did you brush your teeth
      last?" is recommended in order to find out wether your patient is pregnant and to
      get to know her dental care better. 2. Know your audience: Mothers are
      increasingly informed about childbearing, however not every piece of information
      is correct! Let them know what they are doing well and do not sound like you are
      preaching to them. 3. Use informal language. 4. Emphasize the need to get dental
      treatments and to prevent decay: Parents can pass bacteria to their newborns,
      therefore we want mothers to have a healthy mouth before they give birth! 5. Mom
      and dad as first dentists: Teach parents about nutrition and when and how to
      clean their children's mouth. 6. Listen to patients and confirm what they heard:
      Ask the patient to tell you what she is going to do at home and confirm. As
      pregnant women are more receptive to oral health information than in any other
      moment in their life, our aim is to take this opportunity by providing good
      prevention information and instilling healthy habits as early as possible.

PMID- 28494595
TI  - Clinical performance of a glass ionomer sealant protected with two different
      resin-based agents over a 2-year follow-up period.
AB  - AIM: To evaluate the effects of two different resin coating materials on the
      clinical performance of a conventional glass ionomer sealant. MATERIALS AND
      METHODS: Permanent first mandibular molars of 60 children aged 6-9 years were
      sealed with Fuji VII. In each child, G-Coat Plus coating agent was applied to
      molars on one side and Heliobond coating agent to molars on the opposite side of
      the mouth. Clinical evaluations were carried out at 1, 6, 12, 18 and 24 months
      after sealant and coating application. RESULTS: At 1, 6, 12, 18 and 24 months
      after sealant and coating application, total sealant retention rates were 88%,
      40%, 19%, 15% and 9% for molars coated with G-Coat Plus, and 93%, 47%, 17%, 15%
      and 7% for those coated with Heliobond. The differences between the two coating
      agents were not statistically significant (p>0.05). No incidence of caries was
      observed in either group during the two-year evaluation period. STATISTICS:
      Wilcoxon signed rank test was used to compare differences in retention rates and
      caries incidence by coating agent. CONCLUSION: Although retention rates of Fuji
      VII were relatively low and similar for both resin coating agents tested, dental
      caries were not observed in either group during the 24-month study period. In
      children with a high risk of caries and partially erupted molars, the use of a
      glass ionomer sealant with a resin-based coating agent should be encouraged.

PMID- 28494596
TI  - Dental caries, parents educational level, family income and dental service
      attendance among children in Italy.
AB  - AIM: The aim of this study was to verify whether socioeconomic determinants, such
      as parents' educational level, family income and dental service attendance by
      children, are associated with the presence of caries among an Italian population
      of children. MATERIALS AND METHODS: An observational retrospective study was
      carried out in a population of children aged 4-14 years who visited the
      Paediatric Dentistry Department of the University of Perugia, Italy. Children
      were stratified according to familial socioeconomic level (father's and mother's
      educational level, family income) and dental service attendance of children. Age-
      and sex- adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were
      calculated by means of multivariate logistic regression models. RESULTS: A sample
      of 231 children (mean age 8.1 yrs, SD 2.6; 127 males, 104 females) was recruited.
      One hundred and sixty three (70.46%) children in the study had caries. Caries
      presence in children was higher in children where the mothers' educational level
      was lower (OR =6.1; 95% CI = 3.1 to 12.7), in children where the fathers'
      educational level was lower (OR =2.9; 95% CI =1.6 to 5.5) and in children with
      lower family income (OR = 9.9; 95% 95% CI = 5.1 to 20.1). No statistically
      significant difference were observed in terms of caries presence between the
      children who were visited at least once by a dentist and children who were not
      previously seen by a dental practitioner (OR = 0.8; 95% CI = 0.4 to 1.6).
      CONCLUSION: Socioeconomic level was an important predictor of caries presence
      among children. Both low income and low parental educational level were related
      to an increased presence of caries, whereas previous dental visits experience did
      not affect caries presence in children.

PMID- 28494597
TI  - Surgical management of impacted primary teeth: report of two cases.
AB  - AIM: Impaction of deciduous teeth is an uncommon event. The purpose of this
      report is to describe two unusual eruption failures of a second primary molar and
      their treatment management. CASE REPORT: The diagnostic and therapeutic protocol
      of two cases selected at the Unit of Paediatric Dentistry, Department of Oral and
      Maxillofacial Science, "Sapienza" University of Rome, Italy, are presented. In
      both cases, the second deciduous molar was impacted, while no mechanical obstacle
      like odontomas or supernumerary teeth were present. CONCLUSION: The two case
      reports presented in this work are of scientific relevance, due to the rarity of
      this type of pathology.

PMID- 28494598
TI  - Dental trauma in Italian children and adolescents with special health care needs.
      A cross-sectional retrospective study.
AB  - AIM: Dental trauma is a frequent finding in people with special health care
      needs. The aim of this study was to determine the prevalence of dental trauma in
      a sample of Italian children and adolescents with special health care needs.
      MATERIALS AND METHODS: 556 medical and dental records of children and adolescents
      visited from January 2010 to March 2015 were examined. Information about medical
      diagnosis, gender, site and type of dental trauma (DT) were collected. According
      to age and reflecting the dentition stage, the sample was divided into 3 groups:
      subjects aged 0-5 years (group A, primary dentition), 6-11 years (group B, mixed
      dentition), 12-18 years (group C, permanent dentition). RESULTS: 113 individuals
      experienced a DT (prevalence 20.3%), with no difference in relation to gender.
      Individuals with cerebral palsy and autism showed the highest frequency of DT:
      39.6% and 30.4%, respectively. The highest frequency of DT occurred both in group
      A (21.8%) and B (21.5%), which differed significantly from group C (9%). Avulsion
      was the most frequent type of DT in the primary dentition (24%) and enamel-dentin
      fracture without pulp exposure in the permanent dentition (60%). Upper central
      incisors were the most affected teeth. CONCLUSION: The prevalence of DT in a
      sample of Italian children and adolescents with special health care needs is
      high, especially in young individuals with cerebral palsy and autism. Preventive
      strategies for those patients should be developed in order to reduce the risk of
      DT.

PMID- 28494599
TI  - A combined approach with passive and active repositioning of a traumatically
      intruded immature permanent incisor.
AB  - BACKGROUND: Severe damage to the tooth, periodontal ligament, and pulpal tissue
      often occurs with intrusive luxation, and outcomes are quite unpredictable
      because of the variable ways in which the injury may occur, which influences both
      the choice of treatment and prognosis. CASE REPORT: This case presents a novel
      method for the management of an intruded permanent maxillary central incisor with
      an immature apex. At first, watchful waiting for spontaneous re-eruption was the
      chosen treatment option. A palatal gingivectomy was performed and endodontic
      access was established, following which, an intracanal medicament of calcium
      hydroxide was applied. A root canal treatment was completed, and apexification
      with mineral trioxide aggregate was performed. Re-eruption failed to reach
      completion, so complete repositioning was performed with the aid of orthodontics
      for two months. CONCLUSION: The present case illustrates the partial re-eruption
      of a severely intruded immature permanent tooth with the use of interim
      medication in the root canal. This case also shows complete re-eruption with the
      aid of timely orthodontic repositioning after apexification.

PMID- 28494600
TI  - Cephalometric changes after headgear anchored to the deciduous second molars in
      the early mixed dentition.
AB  - AIM: The present study aimed to evaluate the cephalometric effects of a headgear
      anchored to the deciduous second molars in the early mixed dentition. MATERIALS
      AND METHODS: Study design: The study followed a retrospective longitudinal design
      and enrolled 31 consecutive patients (17 females and 14 males) treated with high
      pull (HP) headgear anchored to the deciduous second molars, average age 8y 5m+/-
      5m at pre-treatment time (T0) and 9y 8m+/- 6m at post-treatment time (T1). All
      the patients wore the headgear for approximately 8-10 hours at night, with a
      force of 250 g per side. The active phase of treatment ended once patients
      obtained a distal step on permanent molars of at least 2 mm. Lateral cephalograms
      at T0 and T1 were taken; 10 angular measurements were chosen as variables of the
      study. The paired sample t-test was employed to assess the significance of the
      differences of each variable between T0 and T1. RESULTS AND CONCLUSION: In this
      group of Class II patients, HP headgear anchored to the deciduous second molars
      in the early mixed dentition produced: significant reduction of SNA angle,
      significant increase of SN/NL angle with no significant change in SN/ML angle,
      significant labial flaring of upper incisors. As clinically evaluated, the
      correction of the Class II occlusal relationship and the anterior crowding of
      maxillary arch were also accomplished.

PMID- 28494601
TI  - Relationship between oro and nasopharynx permeability and the direction of facial
      growth.
AB  - AIM: Most scientific literature relates vertical growth to individuals with
      decreased upper airway permeability. However, we often find subjects with a long
      face and a normal breathing pattern, most likely caused by other aetiological
      factors. And, frequently, we also find decreased upper airway permeability with
      horizontal growth. The aim of the study was to compare the cephalometric
      measurements of the oro and nasopharynx permeability with the facial growth
      direction and to identify the most common facial growth direction in individuals
      with decreased upper airway permeability. MATERIALS AND METHODS: Cephalometric
      analysis was carried out in 158 pre-adolescent patients at the Orthodontic
      appointment, using facial profile teleradiographs. Parameters used were Jabarak's
      ratio and measurement of oro-nasopharynx space. Data collected were submitted to
      statistical treatment. RESULTS: This study points to the presence of an
      intermediate growth in individuals with diminished oro and nasopharynx
      permeability, either simultaneous or separate. The number of individuals with
      diminished permeability and vertical growth is close to the number of individuals
      with horizontal growth. CONCLUSIONS: The individuals with diminished permeability
      of the upper airway present an intermediate growth direction, representing the
      most frequent type. In the less common growth directions, there is a slight
      tendency to horizontal facial growth verified in individuals with diminished
      nasopharynx permeability. Also, a light tendency to vertical facial growth is
      present when oropharynx permeability is reduced.

PMID- 28494602
TI  - Are there any differences between first and second primary molar pulpectomy
      prognoses? A retrospective clinical study.
AB  - AIM: To determine if there are any significant differences between the prognoses
      of pulpectomies done on first and second primary molars of the upper and lower
      dental arch. MATERIALS AND METHODS: Study Design: The clinical study included 55
      children who had undergone 86 pulpectomy treatments, 41 on the first molars and
      45 on the second molars. The root canal filling material consisted of a paste
      based on Walkhoff formula, containing Kri-1, calcium hydroxide and meta-cresol
      formaldehyde. The same clinician carried out all pulpectomies. RESULTS: After the
      analysis there were a total of 7 treatment failures (3 in the upper arch and 4 in
      the lower). Four of the 7 failures were first primary molars and three were
      second primary molars. STATISTICS: There were no significant differences in the
      prognoses of the different kinds of primary molars. CONCLUSION: The anatomy of
      the primary molars changes considerably. Significant differences were not
      observed in the prognosis of different types of primary molars after pulpectomy.

PMID- 28494603
TI  - Dental fear and caries in 6-12 year old children in Greece. Determination of
      dental fear cut-off points.
AB  - AIM: To present: the normative data on dental fear and caries status; the dental
      fear cut-off points of young children in the city of Thessaloniki, Greece.
      METHODS: Study Design: This is a cross-sectional study with two independent study
      groups. A first representative sample consisted of 1484 children from 15 primary
      public schools of Thessaloniki. A second sample consisted of 195 randomly
      selected age-matched children, all patients of the Postgraduate Paediatric Dental
      Clinic of Aristotle University of Thessaloniki. First sample: In order to select
      data on dental fear and caries, dental examination took place in the classroom
      with disposable mirrors and a penlight. All the children completed the Dental
      Subscale of the Children's Fear Survey Schedule (CFSS-DS). Second sample: In
      order to define the cut-off points of the CFSS-DS, dental treatment of the 195
      children was performed at the University Clinic. Children&#x2041;s dental fear
      was assessed using the CFSS-DS and their behaviour during dental treatment was
      observed by one calibrated examiner using the Venham scale. STATISTICS:
      Statistical analysis of the data was performed with IBM SPSS Statistics 20 at a
      statistical significance level of <0.05. RESULTS: First sample: The mean CFSS-DS
      score was 27.1&#177;10.8. Age was significantly (p<0.05) related to dental fear.
      Mean differences between boys and girls were not significant. Caries was not
      correlated with dental fear. Second sample: CFSS-DS< 33 was defined as 'no dental
      fear', scores 33-37 as 'borderline' and scores > 37 as 'dental fear'. In the
      first sample, 84.6% of the children did not suffer from dental fear (CFSS-DS<33).
      CONCLUSION: Dental fear was correlated to age and not to caries and gender. The
      dental fear cut-off point for the CFSS-DS was estimated at 37 for 6-12 year old
      children (33-37 borderlines).

PMID- 28494604
TI  - Use of bioactive materials and limited FOV CBCT in the treatment of a replanted
      permanent tooth affected by inflammatory external root resorption: a case report.
AB  - BACKGROUND: Inflammatory external root resorption is one of the possible
      complications of replantation of an avulsed tooth. Several studies have shown
      that limited FOV CBCT is an efficient diagnostic support and in treatment
      planning of these cases in paediatric patients because of its high resolution
      combined with low radiation doses. The recent literature has suggested that
      Biodentine is an effective material for resolution of inflammatory root
      resorption. CASE REPORT: This article describes the successful therapy of a
      replanted tooth affected by inflammatory root resorption. In the present case, a
      CBCT exam was performed to detect the extent of the damage, and the canal was
      filled with Biodentine in the apical third. At present, the threated tooth is
      asymptomatic, and the twelve months follow-up examination showed healing of
      periradicular hard tissues.

PMID- 28494605
TI  - Intra-pulpal and subsurface temperature rise during tooth irradiation with 808 nm
      diode laser: an in vitro study.
AB  - AIM: This in vitro study evaluated the pulpal and subsurface temperatures during
      proximal tooth surface irradiation with different settings of an 808 nm diode
      laser. MATERIALS AND METHODS: The elevation of pulpal and subsurface temperature
      during irradiation was measured using thermocouples positioned in the centre of
      the pulp chamber (n=30) and in the centre of a prepared 1.5 mm deep coronal
      cavity (n=30). Each sample was irradiated 3 times within one-week interval using
      different exposure settings. A temperature increase of 3.5 degrees C was regarded
      as critical value for pulpal heath. Results were analysed with one-way ANOVA and
      Duncan post hoc tests. Micromorphological investigation by digital microscopy was
      carried out for the irradiated and non-irradiated tooth surface. RESULTS
      Measurable temperature increase within the pulp chamber (delta PT) and the
      subsurface (delta ST) were observed with all laser settings tested. The highest
      recorded delta PT and delta ST were 3.1 degrees C and 8.5 degrees C,
      respectively. Delivery mode, beam diameter, and exposure time influenced the
      temperature rise. No alterations on the enamel surface were observed when
      inspected by the digital microscope after undergoing irradiation with the tested
      parameters. Cconclusion: From the thermal point of view, under the conditions of
      the present study the application of an 808 nm diode laser on the outer surface
      of the tooth at 1W in the continuous mode and at 5W in the pulsed mode for two
      cycles of 30 s each proved to be safe.

PMID- 28494606
TI  - Split-mouth design in Paediatric Dentistry clinical trials.
AB  - AIM: The aim of this article was to describe the essential concepts of the split
      mouth design, its underlying assumptions, advantages, limitations, statistical
      considerations, and possible applications in Paediatric Dentistry clinical
      investigation. DISCUSSION: In Paediatric Dentistry clinical investigation, and as
      part of randomised controlled trials, the split-mouth design is commonly used.
      The design is characterised by subdividing the child's dentition into halves
      (right and left), where two different treatment modalities are assigned to one
      side randomly, in order to allow further outcome evaluation. Each participant
      acts as their own control by making within- patient rather than between-patient
      comparisons, thus diminishing inter-subject variability and increasing study
      accuracy and power. However, the main problem with this design comprises the
      potential contamination of the treatment effect from one side to the other, or
      the "carry-across effect"; likewise, this design is not indicated when the oral
      disease to be treated is not symmetrically distributed (e.g. severity) in the
      mouth of children. Thus, in spite of its advantages, the split-mouth design can
      only be applied in a limited number of strictly selected cases. CONCLUSION: In
      order to obtain valid and reliable data from split mouth design studies, it is
      necessary to evaluate the risk of carry-across effect as well as to carefully
      analise and select adequate inclusion criteria, sample-size calculation and
      method of statistical analysis.

PMID- 28494607
TI  - SCN9A channelopathy associated autosomal recessive Congenital Indifference to
      Pain. A case report.
AB  - BACKGROUND: Congenital Indifference to Pain (CIP) is a rare condition that
      inhibits the ability of patients to perceive physical pain but otherwise keeps
      normal sensory modalities. The condition has been mapped to an autosomal
      recessive trait to chromosome 2q 24.3 with mutations on the SCN9A gene. CASE
      REPORT: A 2 year old Caucasian female presented with CIP. Bite injuries, tongue
      wounds and unaccounted dental trauma episodes were frequently reported.
      Preventive instructions and possible treatment modalities were discussed with the
      parents. CONCLUSION: The cornerstone of treating CIP patients is an extensive
      preventive approach alongside regular oral examination at home by parents as well
      as routine recall appointments with dentists.

PMID- 28494608
TI  - Parenteral nutrition in childhood and consequences for dentition and gingivae.
AB  - AIM: Assessment of dentition in children under parenteral nutrition, risk factors
      for caries, and dental developmental abnormalities. MATERIALS AND METHODS: The
      study involved 63 patients (aged 2.25-16.6 years), i.e. 32 subjects receiving
      parenteral nutrition for a mean period of 5.6&#177;2.94 years, and 31 healthy
      control subjects. Oral hygiene (OHI-S, PL-I), gingival (GI), and dentition status
      (caries, DMFT/dmft, enamel defects, shape alterations), frequency of oral meals
      and frequency of cariogenic snacks consumption were evaluated. Medical records
      provided information on parenteral meals per week, age parenteral nutrition
      started, birth body mass, Apgar score, weight deficiency, and antibiotic therapy
      until aged 1 year. The Mann-Whitney test, chi-squared test, and Spearman rank
      correlation coefficient were used (p&#8804;0.05). RESULTS: Dental developmental
      abnormalities occurred more often in PN subjects (71.87% vs. 25.80%). The
      prevalence of caries in PN (56.25% vs. 90.32%) and dmft (2.00&#177;3.30 vs.
      4.21&#177;3.33) and DMFT (2.47&#177;4.08 vs. 3.33&#177;3.50) were lower. Positive
      caries Spearman's rank correlation coefficients: frequency of oral meals and
      frequency of cariogenic snacks consumption, and GI. Negative correlation
      coefficients: low birth body mass, antibiotic therapy, and low body mass in the
      first year of life. Positive dental developmental abnormality Spearman's
      coefficients: low birth body mass, Apgar score < 7, parenteral nutrition
      duration, low body mass and antibiotic therapy in the first year of life. Beta-
      lactam, aminoglycoside, glycopeptide and nitroimidazole treatments were related
      to enamel hypoplasia. CONCLUSION: Parenteral nutrition in childhood is related to
      the risk of dental developmental abnormalities, promoted by malnutrition and
      antibiotic therapy in infancy. Limiting the number of meals and cariogenic
      snacks, and most probably administration of antibiotics, decreases the risk of
      caries.

PMID- 28494609
TI  - Odontomas in developmental age: confocal laser scanning microscopy analysis of a
      case.
AB  - BACKGROUND: Odontomas are the most common benign odontogenic tumors (especially
      in children and adolescents) and consist of odontogenic ectomesenchyma and
      odontogenic epithelium with the formation of dental hard tissues. They are also
      simply considered hamartomas. The WHO Classification defines them as complex and
      compound odontomas. The diagnosis is often occasional, in conjunction with x-ray
      routine examinations, or it is suggested by eruption disorders or abnormal
      position of teeth in the dental arch. The mainstay therapy is surgical excision
      of the lesion followed by orthodontic treatment to take in the arch the impacted
      teeth. CASE REPORT: The aim of this work is the presentation of a case of
      mandibular bilateral compound odontoma in a young patient, and the confocal laser
      scanning microscopic analysis of the surgical specimens.

PMID- 28494610
TI  - Paediatric laser dentistry. Part 1: General introduction.
AB  - AIM: Knowledge of the physical characteristics of different laser lights and
      optical and thermal properties of oral tissues is very important to understand
      the interaction of dental lasers with biological tissues. Choosing the correct
      dental laser is crucial to match specific wavelengths with target chromophores of
      different tissues; this affinity makes laser irradiation selective and therefore
      minimally invasive. Various types of lasers are used in dentistry, offering a
      viable alternative to low and high-speed handpieces and surgical blades, and also
      minimising fear and discomfort of the patient. Lasers can provide innovative and
      minimally invasive therapies in different branches of dentistry including
      preventive and restorative dentistry, traumatic injury treatments and surgical
      procedures. Laser has also biostimulating and anti-inflammatory effects, as well
      as analgesic effect.

PMID- 28494611
TI  - Development of a return-to-work planning tool for cancer survivors: Elaboration
      d'un outil de planification du retour au travail pour les survivants du cancer.
AB  - BACKGROUND: The ability to return to work (RTW) after a cancer diagnosis can
      present significant challenges for survivors and can be an important predictor of
      their long-term quality of life. Survivors report concerns related to disclosing
      their cancer diagnosis, describing ongoing late effects of cancer, and
      negotiating workplace accommodations. PURPOSE: This paper outlines the
      development of an RTW planning template (RTW-PT) designed to improve
      communication with stakeholders involved in the RTW process. Lessons learned
      throughout the process of developing the RTW-PT and implications for clinical
      practice are presented. KEY ISSUES: The RTW-PT assists the survivor and his or
      her health care provider to prioritize job demands during a graded RTW and to
      identify potential accommodations. The RTW-PT also helps survivors plan how they
      will communicate their RTW needs, particularly with employers and insurance
      representatives. IMPLICATIONS: The RTW-PT offers a structured approach to support
      communication among stakeholders involved in the RTW process and to assist
      survivors in negotiating workplace accommodations.

PMID- 28494612
TI  - Oxidative Stress and Inflammation Induced by Environmental and Psychological
      Stressors: A Biomarker Perspective.
AB  - SIGNIFICANCE: The environment can elicit biological responses such as oxidative
      stress (OS) and inflammation as a consequence of chemical, physical, or
      psychological changes. As population studies are essential for establishing these
      environment-organism interactions, biomarkers of OS or inflammation are critical
      in formulating mechanistic hypotheses. Recent Advances: By using examples of
      stress induced by various mechanisms, we focus on the biomarkers that have been
      used to assess OS and inflammation in these conditions. We discuss the difference
      between biomarkers that are the result of a chemical reaction (such as lipid
      peroxides or oxidized proteins that are a result of the reaction of molecules
      with reactive oxygen species) and those that represent the biological response to
      stress, such as the transcription factor NRF2 or inflammation and inflammatory
      cytokines. CRITICAL ISSUES: The high-throughput and holistic approaches to
      biomarker discovery used extensively in large-scale molecular epidemiological
      exposome are also discussed in the context of human exposure to environmental
      stressors. FUTURE DIRECTIONS: We propose to consider the role of biomarkers as
      signs and to distinguish between signs that are just indicators of biological
      processes and proxies that one can interact with and modify the disease process.
      Antioxid. Redox Signal. 28, 852-872.

PMID- 28494613
TI  - New natural product -an efficient antimicrobial applications of new newly
      synthesized pyrimidine derivatives by the electrochemical oxidation of hydroxyl
      phenol in the presence of 2-mercapto-6-(trifluoromethyl) pyrimidine-4-ol as
      nucleophile.
AB  - Some new pyrimidine derivatives have been synthesised by electrochemical
      oxidation of catechol (1a) in the existence of 2-mercapto-6-(trifluoromethyl)
      pyrimidine-4-ol (3) as a nucleophile in aqueous solution using Cyclic
      Voltammetric and Controlled Potential Coulometry. The catechol has been oxidised
      to o-quinone through electrochemical method and participative in Michael addition
      reaction, leading to the development of some new pyrimidine derivatives. The
      products were achieved in good yield with high pureness. The mechanism of the
      reaction has been conformed from the Cyclic Voltammetric data and Controlled
      Potential Coulometry. After purification, the compounds were characterised using
      modern techniques. The synthesised materials were screened for antimicrobial
      actions using Gram positive and Gram negative strain of bacteria. These new
      synthesised pyrimidine derivatives showed very good antimicrobial activity.

PMID- 28494614
TI  - Evaluation of pigments from methanolic extract of Tagetes erecta and Beta
      vulgaris as antioxidant and antibacterial agent.
AB  - The Total Phenolic Content (TPC), antioxidant and antibacterial activities of
      methanolic extract of Marigold flower (MF) (Tagetes erecta) and Beet root (BR)
      (Beta vulgaris) were examined. The present work reveals that MF contained greater
      amount of TPC (42.5 mg/g GAE) as compared to BR (39.4 mg/g GAE). Methanolic
      extract of MF exhibited excellent DPPH free radical scavenging power (IC50 0.0716
      mg/mL) and reducing power at 1 mg/mL concentration. Similar results have been
      obtained in FTC and TBA method. The results of antibacterial test indicated that
      the methanolic extract of MF and BR is significantly effective against both type
      of Gram-negative (Escherichia coli, Shigella dysenteriae) and Gram-positive
      (Bacillus subtilis, Staphylococcus aureus) bacterial strains. Therefore, the
      present study suggests that the Marigold and BR are promising source of herbal
      medicinal products with noteworthy antioxidant and antibacterial activity.

PMID- 28494615
TI  - Effects of time perspective and self-control on procrastination and Internet
      addiction.
AB  - Background and aims College students experiencing stress show tendencies to
      procrastinate and can develop Internet addiction problems. This study
      investigated the structural relationship between time perspective and self
      control on procrastination and Internet addiction. Methods College students (N =
      377) residing in South Korea completed the following questionnaires: the
      Pathological Internet Use Behavior Symptom Scale for Adults, the Zimbardo Time
      Perspective Inventory, the Self-Control Rating Scale, and the Aitken
      Procrastination Inventory. The sample variance-covariance matrix was analyzed
      using AMOS 20.0. Results Time perspective had a direct effect on self-control and
      an indirect effect on Internet use and procrastination. In addition, self-control
      affected procrastination and Internet use. Conclusions Individuals with a present
      oriented time perspective tend to evidence poorer self-control, increasing the
      likelihood of procrastination and Internet addiction. Individuals with a future
      oriented time perspective, on the other hand, tend to have stronger self-control,
      decreasing their risk of procrastination and Internet addiction.

PMID- 28494616
TI  - Breakdown of Thalamo-Cortical Connectivity Precedes Spike Generation in Focal
      Epilepsies.
AB  - Electroencephalography (EEG) spikes and focal epileptic seizures are generated in
      circumscribed cerebral networks that have been insufficiently described. For
      precise time and spatial domain network characterization, we applied in patients
      with focal epilepsy dense array 256-channel EEG recordings with causal
      connectivity estimation by using time-resolved partial directed coherence and 3T
      magnetic resonance imaging-derived cortical and thalamus integrity
      reconstruction. Before spike generation, significant theta and alpha bands driven
      information flows alterations were noted from both temporal and frontal lobes to
      the thalamus and from the thalamus to the frontal lobe. Medial dorsal and ventral
      anterior nuclei of the thalamus were delimited as possible pacemakers. Markedly
      reduced thalamic volumes and impaired cortical integrity in widespread areas
      predicted the altered information flows. Our data reveal distinct patterns of
      connectivity involving the thalamus and frontal cortex that are both directly and
      causally involved in spike generation. These structures might play an essential
      role in epileptogenesis and could be targeted in future therapeutic approaches.

PMID- 28494617
TI  - First report of the in vitro antileishmanial properties of extremophile plants
      from the Algarve Coast.
AB  - This work reports for the first time the in vitro anti Leishmania infantum
      activity of acetone and dichloromethane (DCM) extracts from 25 extremophile
      plants from Southern Portugal. DCM extracts from Inula chritmoides and
      Spergularia rubra were active against axenic promastigotes and intracellular
      amastigotes, had anti-inflammatory properties on lipopolysaccharide (LPS)
      stimulated macrophages, inhibited acetylcholinesterase and had no haemolytic
      activity on human erythrocytes. Eleven phenolics were identified by high
      performance liquid chromatography with diode-array detection (HPLC-DAD) in I.
      crithmoides and one phenolic in S. rubra. Isolation and identification of the
      active molecules is in progress.

PMID- 28494618
TI  - Machine Learning Methods to Predict Diabetes Complications.
AB  - One of the areas where Artificial Intelligence is having more impact is machine
      learning, which develops algorithms able to learn patterns and decision rules
      from data. Machine learning algorithms have been embedded into data mining
      pipelines, which can combine them with classical statistical strategies, to
      extract knowledge from data. Within the EU-funded MOSAIC project, a data mining
      pipeline has been used to derive a set of predictive models of type 2 diabetes
      mellitus (T2DM) complications based on electronic health record data of nearly
      one thousand patients. Such pipeline comprises clinical center profiling,
      predictive model targeting, predictive model construction and model validation.
      After having dealt with missing data by means of random forest (RF) and having
      applied suitable strategies to handle class imbalance, we have used Logistic
      Regression with stepwise feature selection to predict the onset of retinopathy,
      neuropathy, or nephropathy, at different time scenarios, at 3, 5, and 7 years
      from the first visit at the Hospital Center for Diabetes (not from the
      diagnosis). Considered variables are gender, age, time from diagnosis, body mass
      index (BMI), glycated hemoglobin (HbA1c), hypertension, and smoking habit. Final
      models, tailored in accordance with the complications, provided an accuracy up to
      0.838. Different variables were selected for each complication and time scenario,
      leading to specialized models easy to translate to the clinical practice.

PMID- 28494619
TI  - Improving quality of care for end-stage respiratory disease: Changes in attitude,
      changes in service.
AB  - The illness trajectory for many patients with severe respiratory disease is
      characterized by steady decline. Yet most healthcare resources are poured into
      managing acute exacerbations that are only temporarily effective. Further, 'bad
      deaths' can result from inappropriate medical interventions at times of crisis.
      In this article, we describe a range of changes in attitudes, behaviour and
      service provision that together focus on improving quality of care for
      respiratory patients with frequent crises. These changes include prognostic
      conversations, developing and implementing anticipatory care plans both in
      hospital and in the outpatient settings, and establishing a supportive care
      clinic devoted to complex disease and optimizing palliative care. The
      underpinning philosophy is that common sense and compassion should motivate
      broader and more flexible care much more than adherence to the 'curative
      restorative' guidelines-based model.

PMID- 28494620
TI  - Genetic testing improves identification of transthyretin amyloid (ATTR) subtype
      in cardiac amyloidosis.
AB  - Amyloidosis is a group of conditions characterized by the accumulation of amyloid
      deposits in various tissues. Among these disorders, ATTR amyloidosis occurs
      either with or without a TTR pathogenic variant. Treatment for amyloidosis
      depends on the subtype, which is often identified through a tissue biopsy
      followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Genetic
      testing may be done to confirm these results for patients with ATTR amyloidosis;
      however, the necessity of genetic testing after LC-MS/MS has not been evaluated.
      A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR
      amyloidosis, and 56 of these patients underwent both genetic testing and LC
      MS/MS. LC-MS/MS and proteomics correctly reported the mutant peptide and
      heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who
      were homozygous for the ATTRV122I mutation and failed to detect the following
      mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and
      ATTRV122I. Therefore, LC-MS/MS is not sufficient to rule out a pathogenic
      mutation in cases of ATTR amyloid, and genetic testing should be performed in
      most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR
      amyloidosis is important for estimating prognosis, proper familial counselling
      and guiding use of therapies, such as liver transplantation.

PMID- 28494621
TI  - Chinese cross-cultural adaptation and validation of the Foot Function Index as
      tool to measure patients with foot and ankle functional limitations.
AB  - PURPOSE: To perform a cross-cultural adaptation and validation of the Foot
      Function Index (FFI) questionnaire to develop the Chinese version. MATERIALS AND
      METHODS: Three hundred and six patients with foot and ankle neuromusculoskeletal
      diseases participated in this observational study. Construct validity, internal
      consistency and criterion validity were calculated for the FFI Chinese version
      after the translation and transcultural adaptation process. RESULTS: Internal
      consistency ranged from 0.996 to 0.998. Test-retest analysis ranged from 0.985 to
      0.994; minimal detectable change 90: 2.270; standard error of measurement: 0.973.
      Load distribution of the three factors had an eigenvalue greater than 1. Chi
      square value was 9738.14 (p < 0.001). Correlations with the three factors were
      significant between Factor 1 and the other two: r = -0.634 (Factor 2) and r = 
      0.191 (Factor 1). Foot Function Index (Taiwan Version), Short-Form 12 (Version 2)
      and EuroQol-5D were used for criterion validity. Factors 1 and 2 showed
      significant correlation with 15/16 and 14/16 scales and subscales, respectively.
      CONCLUSIONS: Foot Function Index Chinese version psychometric characteristics
      were good to excellent. Chinese researchers and clinicians may use this tool for
      foot and ankle assessment and monitoring. Implications for rehabilitation A cross
      cultural adaptation of the FFI has been done from original version to Chinese.
      Consistent results and satisfactory psychometric properties of the Foot Function
      Index Chinese version have been reported. For Chinese speaking researcher and
      clinician FFI-Ch could be used as a tool to assess patients with foot disease.

PMID- 28494622
TI  - Presence of inflammatory proteins S100A8 and S100A9 in a giant intracranial
      aneurysm after flow diverter treatment.
AB  - We demonstrate the presence of S100A8 and S100A9 proteins in the wall and
      thrombosed lumen of an enlarged intracranial aneurysm after flow diverter
      treatment. These proteins have shown to play an important role in vascular
      inflammation and may serve as a biomarker and potential therapeutic target for
      intracranial aneurysms.

PMID- 28494623
TI  - Validity of the Wisconsin Card Sorting Test in patients with stroke.
AB  - BACKGROUND: The Wisconsin Card Sorting Test (WCST) is the most widely used
      measure for assessing executive functions in patients with stroke. However, no
      study has examined the ecological, discriminative and convergent validities of
      the WCST in patients with stroke. This study aimed to examine the above
      validities of the WCST in patients with stroke. METHODS: Ninety-eight patients
      were administered the WCST, two measures of activities of daily living and one
      cognitive measure. Seven indexes of the WCST were used in this study. RESULTS:
      Two WCST indexes ("total number correct" and "number of categories completed")
      had moderate correlations with two measures of activities of daily living
      (Pearson's r = 0.39-0.49). The other indexes showed low or moderate correlations
      with two measures of activities of daily living (r = 0.26-0.53). The results of
      independent t-test showed statistically significant difference between patients
      with and without disability for the seven WCST indexes (p = 0.001-0.013) and
      nonsignificant differences between patients with different affected regions of
      the brain (p > 0.05). Moderate correlations (r = 0.35-0.54) were found among the
      seven WCST indexes and one cognitive measure. CONCLUSIONS: The WCST has poor to
      adequate ecological validity, acceptable discriminative validity and acceptable
      convergent validity in patients with stroke. The two WCST indexes ("total number
      correct" and "number of categories completed") are recommended for use to reflect
      the degree of living independence in patients with stroke. Implications for
      rehabilitation The Wisconsin Card Sorting Test showed poor to adequate ecological
      validity, acceptable discriminative validity, and acceptable convergent validity
      in patients with stroke. Two indexes of the Wisconsin Card Sorting Test (i.e.,
      "total number correct" and "number of categories completed") can adequately
      reveal the degrees of living independence in patients with stroke.

PMID- 28494624
TI  - An Overview of the Performance Improvement Initiatives by the Ministry of Health
      in the Kingdom of Saudi Arabia.
AB  - Saudi Arabia's Ministry of Health (MOH) use corporate performance improvement
      methodologies to develop and implement performance improvement initiatives
      designed to continue building on the Ministry's vision of transforming hospital
      operations and instituting a culture of quality and performance focused on the
      "patient first" principle. We evaluated the feasibility of setting up a
      performance improvement unit (PIU) within the MOH to apply the principles of Lean
      Six Sigma and to change management methodologies. The MOH collaborated with
      external consultants to implement PIU initiatives in 4 steps: PIU Setup, PIU
      Capability Building, High-Impact Project Implementation, and Project
      Sustainability and Knowledge Transfer. PIU units were setup across the 13
      provinces over 90 days. The process included the promotion of knowledge sharing
      to strengthen the skill set of Saudi health care professionals and develop local
      performance improvement champions within the MOH who could lead, implement, and
      sustain future projects. Implementation was a challenge; though, early results
      from the High-Impact Project Implementation phase were encouraging. However, the
      sustainability of PIU interventions was poor, with performance improvement
      processes returning to baseline levels within 9 months. This case study shows
      that PIU implementation is a feasible approach for improving health care delivery
      in Saudi Arabia. Poor sustainability despite initial success highlights the need
      to further improve the engagement, incentivization, and training of team leaders
      and members to achieve long-term success with the program.

PMID- 28494625
TI  - S100-alarmins: potential therapeutic targets for arthritis.
AB  - INTRODUCTION: In arthritis, inflammatory processes are triggered by numerous
      factors that are released from joint tissues, promoting joint destruction and
      pathological progression. During inflammation, a novel family of pro-inflammatory
      molecules called alarmins is released, amplifying inflammation and joint damage.
      Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the
      pathogenesis of arthritis, recent advances and the future prospects in terms of
      therapeutic implications are considered. Expert opinion: There is still an urgent
      need for novel treatment strategies addressing the local mechanisms of joint
      inflammation and tissue destruction, offering promising therapeutic alternatives.
      S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are
      endogenous triggers of inflammation, defining these proteins as promising targets
      for local suppression of arthritis. In murine models, the blockade of
      S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there
      are several lines of evidence that S100-alarmins may already be targeted in
      therapeutic approaches in man.

PMID- 28494626
TI  - Desoximetasone 0.25% spray, adrenal suppression and efficacy in extensive plaque
      psoriasis.
AB  - BACKGROUND: In extensive psoriasis, topical corticosteroids are generally only
      used to supplement phototherapy and systemic therapy. Spray formulations are
      easier than other vehicle preparations to apply and may be an option for treating
      extensive psoriasis. OBJECTIVE: To evaluate the potential for hypothalamic
      pituitary-adrenal axis suppression and efficacy of topical desoximetasone 0.25%
      spray formulation in patients with extensive psoriasis. METHODS: A multicenter,
      open label, nonrandomized, clinical trial was conducted. Two groups of 12 adults
      with moderate to severe plaque-type psoriasis were treated with 0.25%
      desoximetasone spray for 28 days. Physician global assessment (PGA) and body
      surface area (BSA) were assessed. Cortisol-induced suppression test was performed
      at baseline, day 14 and day 28 to assess safety. RESULTS: No statistically
      significant difference was seen in adrenal suppression; odds ratio of 0.779 (p =
      .85). The mean PGA improvement from baseline was 1.83 and 1.33 for moderate and
      severe psoriasis, respectively. Mean BSA involvement at baseline for moderate and
      severe psoriasis was 11% and 23%, respectively, improving to 5% and 19%,
      respectively. CONCLUSIONS: Considerable improvement can be achieved with short
      term potent topical corticosteroid treatment even in patients with severe,
      extensive psoriasis. For such use, topical desoximetasone has less risk of HPA
      suppression than does topical clobetasol.

PMID- 28494627
TI  - Problem-based learning in occupational therapy curriculum - implications and
      challenges.
AB  - PURPOSE: Problem-based learning (PBL) is an educational method that fosters self
      directed study in small groups. The purpose of this study was to describe the Tel
      Aviv University's occupational therapy (OT) program and the challenges
      implementing such program. In addition, the study compared the PBL grades
      obtained by students who are native Hebrew speakers with those students who are
      native Arabic speakers; and, assessed the correlation between the grades in the
      PBL course and the grades in the clinical fieldwork studies. METHOD: 166-second
      year OT undergraduate students participated. All completed three PBL courses and
      seven weeks of clinical fieldwork studies. Data collection included students'
      grades in PBL course (based on PBL evaluation forms) and in clinical fieldwork
      studies (based on preceptor's evaluation and a written assignment). RESULTS:
      Pearson correlations revealed significant correlations between PBL grades and
      clinical fieldwork studies grades. T-test analysis between students who are
      native Hebrew speakers and those who are native Arabic speakers revealed
      significant differences in PBL grades. CONCLUSIONS: Findings imply partial
      congruence between students' grades in the PBL course and their achievements in
      the fieldwork studies. Findings might suggest that adjustments should be made in
      order to assist students from minorities (challenged by language requirements) in
      gaining higher grades in the PBL program. Implications for Rehabilitation Problem
      Based Learning (PBL) is an educational method, which fosters independent, self
      directed study in small groups. PBL studies have the potential to prepare
      students for their clinical experience during studies. The PBL program should be
      adjusted for students from minorities (challenged by language requirements and
      different cultural backgrounds) in order to assist them in gaining more benefits
      from the program.

PMID- 28494628
TI  - Probabilistic risk assessment of emerging materials: case study of titanium
      dioxide nanoparticles.
AB  - The development and use of emerging technologies such as nanomaterials can
      provide both benefits and risks to society. Emerging materials may promise to
      bring many technological advantages but may not be well characterized in terms of
      their production volumes, magnitude of emissions, behaviour in the environment
      and effects on living organisms. This uncertainty can present challenges to
      scientists developing these materials and persons responsible for defining and
      measuring their adverse impacts. Human health risk assessment is a method of
      identifying the intrinsic hazard of and quantifying the dose-response
      relationship and exposure to a chemical, to finally determine the estimation of
      risk. Commonly applied deterministic approaches may not sufficiently estimate and
      communicate the likelihood of risks from emerging technologies whose uncertainty
      is large. Probabilistic approaches allow for parameters in the risk assessment
      process to be defined by distributions instead of single deterministic values
      whose uncertainty could undermine the value of the assessment. A probabilistic
      approach was applied to the dose-response and exposure assessment of a case study
      involving the production of nanoparticles of titanium dioxide in seven different
      exposure scenarios. Only one exposure scenario showed a statistically significant
      level of risk. In the latter case, this involved dumping high volumes of nano
      TiO2 powders into an open vessel with no personal protection equipment. The
      probabilistic approach not only provided the likelihood of but also the major
      contributing factors to the estimated risk (e.g. emission potential).

PMID- 28494629
TI  - Cisplatin and paclitaxel co-delivered by folate-decorated lipid carriers for the
      treatment of head and neck cancer.
AB  - CONTEXT: For head and neck cancer therapy, co-delivery of two drugs, cisplatin
      (DDP) plus paclitaxel (PTX), are more effective than single drug therapy. Lipid
      carriers are promising drug carriers for anti-cancer delivery. OBJECTIVE: The aim
      of this study is to construct a folate (FA) decorated nanostructured lipid
      carriers (NLCs) as nanocarriers for DDP and PTX delivery. MATERIALS AND METHODS:
      In this study, DDP and PTX were incorporated into NLCs. Folate-PEG-DSPE (FA-PEG
      DSPE) was synthesized and decorated the drugs-loaded NLCs (FA-DDP/PTX NLCs).
      Their average size, zeta potential, drug encapsulation efficiency, drug loading
      capacity, and in vitro drug release were evaluated. Head and neck cancer cells
      (FaDu cells) were used for the testing of in vitro cytotoxicity, and in vivo
      transfection efficiency of NLC was evaluated on mice bearing FaDu cells model.
      RESULTS: The size of FA-DDP/PTX NLCs was around 127 nm, with a positive zeta
      potential of 26.7 mV. FA-DDP/PTX NLCs showed the highest cytotoxicity and
      synergistic effect of two drugs in head and neck cancer cells (FaDu cells) in
      vitro. The in vivo study revealed the greatest anti-tumor activity than all the
      other formulations in murine-bearing head and neck cancer model. DISCUSSION AND
      CONCLUSION: FA-DDP/PTX NLCs effectively improves anticancer efficiency for head
      and neck cancer in vitro and in vivo. The constructed NLCs could be used as a
      novel carrier to co-delivery DDP and PTX for head and neck cancer therapy.

PMID- 28494630
TI  - Harnessing public domain data to discover and validate therapeutic targets.
AB  - INTRODUCTION: Discovering, developing and validating new disease treatments is a
      challenging and time-consuming endeavor. Successful drug discovery hinges on
      selecting the best drug targets with relevance to human disease and evidence that
      modulating them will be beneficial for patients. Open data initiatives are
      increasingly placing such knowledge into the public domain. Areas covered: In
      this review, the authors discuss emerging resources such as Open Targets which
      integrate key information to prioritize target-disease connections. Researchers
      can use it, along with other resources, to select potential new therapeutic
      targets to initiate drug discovery projects. They also discuss public resources
      such as DrugBank and ChEMBL that offer potential tools to interrogate these
      targets. Expert opinion: In our opinion, publically available resources are
      democratizing and connecting information, enabling disease experts to access and
      prioritize targets of interest in ways that were not possible a few years ago.
      Moreover, there are several modalities in addition to small molecule perturbation
      to modulate a target's activity. Drug discovery scientists can now utilize these
      new resources to simultaneously evaluate a much larger number of targets than
      previously possible.

PMID- 28494631
TI  - Learning from the failures of drug discovery in B-cell non-Hodgkin lymphomas and
      perspectives for the future: chronic lymphocytic leukemia and diffuse large B
      cell lymphoma as two ends of a spectrum in drug development.
AB  - INTRODUCTION: Despite substantial recent advances, there is still an unmet need
      for better therapies in B-cell non Hodgkin lymphomas (B-NHL), especially in
      relapsed or refractory disease. Many novel targeted drugs have been developed
      based on a better molecular understanding of B-NHL. Areas covered: This article
      focuses on chronic lymphocytic leukemia (CLL) as a representative for indolent
      lymphomas and paradigmatic for the tremendous progress in treating B-NHL on the
      one hand and diffuse large B-cell lymphoma (DLBCL) as a representative for
      aggressive lymphomas and paradigmatic for many unsolved problems in lymphoma
      treatment or the other hand. We highlight salient points in current therapies
      targeting genetic, epigenetic, immunological and microenvironmental alterations.
      Possible reasons for drug failure in clinical trials like tumor heterogeneity,
      clonal evolution and drug resistance mechanisms are discussed. Based thereon,
      some perspectives for further drug discovery are given. Expert opinion: In view
      of the pathogenetic complexity of lymphomas, therapies targeting exclusively a
      single alteration may fail because resistance mechanisms are present either
      initially or evolve during treatment. Therefore, future therapies in B-NHL may
      have to target the greatest possible number of genetic, immunological or
      epigenetic alterations still allowing tolerability and to monitor these
      alterations during therapy.

PMID- 28494632
TI  - Children's and teachers' perspectives on adjustments needed in school settings
      after acquired brain injury.
AB  - BACKGROUND: Children with acquired brain injury (ABI) often present with
      functional deficits that influence their societal participation and well-being.
      Successful reintegration into school calls for individual support to meet each
      child's adjustment needs. The adjustment needs of children with ABI in school
      settings have not previously been explored. AIM: The objectives of the present
      study were (a) to describe adjustment needs in school settings for children with
      ABI and (b) to explore differences and similarities between reports from the
      children and their teachers. METHODS: In this cross-sectional study, 20 children
      with ABI (mean age 12.8 +/- 3.4 years; class grade 1-10) and their teachers were
      interviewed individually, using the School Setting Interview (SSI). Data were
      analyzed with descriptive and with non-parametric statistics. RESULTS: (a) In the
      overall group, children rated that 55.6% of the 16 activities in the SSI needed
      no adjustment. The corresponding percentage for teachers was 48.4%. (b) In the
      child-teacher pairs, there was a positive relationship between teachers' and
      children's responses only in 3 out of 16 school activities and agreement varied
      strongly according to the activity in question. CONCLUSIONS AND SIGNIFICANCE: It
      is important for occupational therapists and other professionals to specifically
      consider adjustment needs relating to school activities from various perspectives
      when aiming to provide individualized interventions.

PMID- 28494633
TI  - Comparison of in-clinic point-of-care and reference laboratory total thyroxine
      immunoassays for diagnosis and post-treatment monitoring of hyperthyroid cats.
AB  - Objectives The Catalyst One Chemistry Analyzer (IDEXX Laboratories) is a point-of
      care instrument that can measure total thyroxine (TT4) by immunoassay. The aims
      of this study were to evaluate the analytic performance of the Catalyst TT4 assay
      in feline sera and to examine agreement of the Catalyst TT4 results with those
      measured by immunoassay at a veterinary reference laboratory. Methods Assay
      precision, reproducibility and linearity were evaluated for the Catalyst TT4
      assay. For method comparison, TT4 concentrations in serum samples from 157 cats
      (127 hyperthyroid, 30 radioiodine-treated cats) were analyzed by both in-clinic
      and reference laboratory methods. Results The Catalyst TT4 demonstrated good
      precision and reproducibility (coefficients of variation ?8.5%) and excellent
      linearity in the diagnostic range of 6-150 nmol/l. Differences between the two
      TT4 methods showed no proportional or fixed bias (Bland-Altman plots) but did
      demonstrate greater spread of values at higher TT4 concentrations. Statistical
      analysis of percent differences between methods indicated 95% limits of agreement
      of +/- 30%. When serum TT4 concentrations were classified as low, high or within
      the reference interval (12-50 nmol/l) for each assay, there was strong agreement
      (96.8%) in classification between methods. Conclusions and relevance The Catalyst
      TT4 assay provided precise serum TT4 concentrations in the 157 samples analyzed,
      which agreed well with results provided by a reference laboratory. Cats with
      Catalyst TT4 concentrations near decision thresholds (eg, normal vs high) should
      either have TT4 concentration repeated a few weeks later and/or undergo further
      testing (eg, free T4, serum thyroid-stimulating hormone, thyroid scintigraphy) to
      determine thyroid status.

PMID- 28494635
TI  - Trends in Management and Mortality in Adults Hospitalized With Cardiac Arrest in
      the United States.
AB  - BACKGROUND: We sought to examine temporal trends in management (ie, use of
      extracorporeal membrane oxygenation [ECMO], therapeutic hypothermia [TH],
      coronary angiogram, and percutaneous coronary intervention [PCI]) and in-hospital
      mortality in adults hospitalized with cardiac arrest. METHODS: Utilizing the
      Nationwide Inpatient Sample, medical history, clinical management, and in
      hospital mortality were assessed in 942 495 hospitalizations in adults with
      cardiac arrest (identified through International Classification of Diseases-9
      codes) from 2006 to 2012. RESULTS: From 2006 to 2012, there was an overall rise
      in the use of coronary angiogram (12.8%, 13.0%, 14.7%, 15.0%, 14.3%, 14.7%, and
      15.8%), PCI (7.5%, 7.1%, 8.4%, 8.1%, 8.1%, 8.4%, and 8.9%), TH (0.2%, 0.3%, 0.6%,
      1.2%, 1.9%, 2.8%, and 3.0%), and ECMO (0.1%, 0.1%, 0.1%, 0.2%, 0.2%, 0.3%, and
      0.4%; P < .001 for all). In-hospital mortality significantly decreased over the 7
      year study period (65.5%, 63.4%, 59.3%, 57.9%, 57.0%, 56.0%, and 56.3% from 2006
      to 2012). In multivariable analysis, a 31% decrease in mortality was accompanied
      by a concomitant 24% and 27% increase in coronary angiogram and PCI,
      respectively, during the study period. Therapeutic hypothermia and ECMO were
      associated with an approximate 11-fold and 7-fold increase, respectively, from
      2006 to 2012. The strongest predictors of use of ECMO, TH, coronary angiogram,
      and PCI were younger age and the presence of coronary artery disease. CONCLUSION:
      During 2006 to 2012, a decline in mortality was accompanied by a steady rise in
      the use of ECMO, TH, coronary angiogram, and PCI in adults hospitalized with
      cardiac arrest. Patients of younger age and with coronary artery disease were
      more likely to receive these advanced therapies.

PMID- 28494634
TI  - Changing place of death in children who died after discharge from paediatric
      intensive care units: A national, data linkage study.
AB  - BACKGROUND: Although child mortality is decreasing, more than half of all deaths
      in childhood occur in children with a life-limiting condition whose death may be
      expected. AIM: To assess trends in place of death and identify characteristics of
      children who died in the community after discharge from paediatric intensive care
      unit. DESIGN: National data linkage study. SETTING/PARTICIPANTS: All children
      resident in England and Wales when admitted to a paediatric intensive care unit
      in the United Kingdom (1 January 2004 and 31 December 2014) were identified in
      the Paediatric Intensive Care Audit Network dataset. Linkage to death certificate
      data was available up to the end of 2014. Place of death was categorised as
      hospital (hospital or paediatric intensive care unit) or community (hospice, home
      or other) for multivariable logistic modelling. RESULTS: The cohort consisted of
      110,328 individuals. In all, 7709 deaths occurred after first discharge from
      paediatric intensive care unit. Among children dying, the percentage in-hospital
      at the time of death decreased from 83.8% in 2004 to 68.1% in 2014; 852 (0.8%) of
      children were discharged to palliative care. Children discharged to palliative
      care were eight times more likely to die in the community than children who died
      and had not been discharged to palliative care (odds ratio = 8.06 (95% confidence
      interval = 6.50-10.01)). CONCLUSIONS: The proportion of children dying in
      hospital is decreasing, but a large proportion of children dying after discharge
      from paediatric intensive care unit continue to die in hospital. The involvement
      of palliative care at the point of discharge has the potential to offer choice
      around place of care and death for these children and families.

PMID- 28494636
TI  - Higher iron bioavailability of a human-like collagen iron complex.
AB  - Iron deficiency remains a public health problem around the world due to low iron
      intake and/or bioavailability. FeSO4, ferrous succinate, and ferrous glycinate
      chelate are rich in iron but have poor bioavailability. To solve the problem of
      iron deficiency, following previous research studies, a thiolated human-like
      collagen-ironcomplex supplement with a high iron content was prepared in an
      anaerobic workstation. In addition, cell viability tests were evaluated after
      conducting an MTT assay, and a quantitative analysis of the thiolated human-like
      collagen-iron digesta samples was performed using the SDS-PAGE method coupled
      with gel filtration chromatography. The iron bioavailability was assessed using
      Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed
      that (1) one mole of thiolated human-like collagen-iron possessed approximately
      35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit
      cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher
      bioavailability than other iron supplements, including FeSO4, ferrous succinate,
      ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the
      iron bioavailability was significantly enhanced by vitamin C. These results
      indicated that thiolated human-like collagen-iron is a promising iron supplement
      for use in the future.

PMID- 28494637
TI  - Does Anxiety Enhance or Hinder Attentional and Impulse Control in Youth With
      ADHD? An ERP Analysis.
AB  - OBJECTIVE: Youth with ADHD and comorbid anxiety (ADHD+ANX) experience increased
      social and academic impairment compared with youth with ADHD without anxiety
      (ADHD). Group differences in attentional and impulse control may underlie this
      increased impairment. Examination of group differences using behavioral measures
      of attentional and impulse control has yielded inconsistent findings. This study
      explored group differences using event-related potentials (ERPs), which provide
      neural information concerning early information processing. METHOD: ERPs (early
      frontal positivity [EFP], N2) were collected while youth aged 11 to 17 with ADHD
      ( n = 31) and ADHD+ANX ( n = 35) completed a visual and an auditory computer
      task. RESULTS: Compared with the ADHD group, the ADHD+ANX group exhibited larger
      N2 amplitudes to no-go stimuli and larger EFP amplitudes to target auditory
      stimuli, with variable attention allocation to nontarget stimuli. CONCLUSION: The
      addition of anxiety to ADHD appears to alter early attentional processing, which
      may be an important aspect of this comorbidity.

PMID- 28494638
TI  - An environmental scan of emergency response systems and services in remote First
      Nations communities in Northern Ontario.
AB  - BACKGROUND: Approximately 24,000 Ontarians live in remote Indigenous communities
      with no road access. These communities are a subset of Nishnawbe Aski Nation
      (NAN), a political grouping of 49 First Nations communities in Northern Ontario,
      Canada. Limited information is available regarding the status of emergency care
      in these communities. OBJECTIVE: We aimed to understand emergency response
      systems, services, and training in remote NAN communities. DESIGN: We used an
      environmental scan approach to compile information from multiple sources
      including community-based participatory research. This included the analysis of
      data collected from key informant interviews (n=10) with First Nations community
      health leaders and a multi-stakeholder roundtable meeting (n=33) in October 2013.
      RESULTS: Qualitative analysis of the interview data revealed four issues related
      to emergency response systems and training: (1) inequity in response capacity and
      services, (2) lack of formalised dispatch systems, (3) turnover and burnout in
      volunteer emergency services, and (4) challenges related to first aid training.
      Roundtable stakeholders supported the development of a community-based emergency
      care system to address gaps. CONCLUSIONS: Existing first response, paramedical,
      and ambulance service models do not meet the unique geographical, epidemiological
      and cultural needs in most NAN communities. Sustainable, context-appropriate, and
      culturally relevant emergency care systems are needed.

PMID- 28494639
TI  - Photocatalytic degradation of polyvinylpyrrolidone in aqueous solution using
      TiO2/H2O2/UV system.
AB  - The photocatalytic degradation of high molecular weight polyvinylpyrrolidone
      (PVP), a water-soluble polymer, using a TiO2/H2O2/UV system was studied in an
      annular photoreactor using a mercury vapor lamp (125 W) as the radiation source.
      The effect of the initial hydrogen peroxide concentration and the operating
      conditions, such as initial concentration of PVP, photocatalyst dosage and
      initial pH, on the reaction rate was also evaluated. It was observed that the
      efficiency of the TiO2/H2O2/UV system was 33% higher than that of a system
      without H2O2, reaching total organic carbon removals of above 80% in 6 h of
      reaction, depending on the experimental conditions. The optimal photocatalyst
      dosage was found to be 0.50 g L-1. Also, the results demonstrate that the
      reaction rate increases as the pH and initial concentration of PVP decrease. This
      treatment can be carried out successfully under optimal conditions and enhance
      the biodegradability of the organic matter remaining at the end of the
      application of the TiO2/H2O2/UV system, as assessed by biochemical oxygen
      demand/chemical oxygen demand measurements.

PMID- 28494640
TI  - Identification of 3-MCPD esters to verify the adulteration of extra virgin olive
      oil.
AB  - The adulteration of olive oil is an important issue around the world. This paper
      reports an indirect method by which to identify 3-monochloropropane-1,2-diol (3
      MCPD) esters in olive oils. Following sample preparation, the samples were spiked
      with 1,2-bis-palmitoyl-3-chloropropanediol standard for analysis using gas
      chromatograph-tandem mass spectrometry. The total recovery ranged from 102.8% to
      105.5%, the coefficient of variation ranged from 1.1% to 10.1%, and the limit of
      quantification was 0.125 mg/kg. The content of 3-MCPD esters in samples of
      refined olive oil (0.97-20.53 mg/kg) exceeded those of extra virgin olive oil
      (non-detected to 0.24 mg/kg). These results indicate that the oil refining
      process increased the content of 3-MCPD esters, which means that they could be
      used as a target compound for the differentiation of extra virgin olive oil from
      refined olive oil in order to prevent adulteration.

PMID- 28494641
TI  - Establishment and Evaluation of Patient-Specific Virtual Ureteroscopy in
      Assisting Flexible Ureteroscopy for Urolithiasis.
AB  - OBJECTIVES: To establish virtual ureteroscopy (VU) through computed tomography
      urography (CTU) data from patients with upper urinary tract (UUT) stones
      indicated for flexible ureteroscopy (fURS) and to validate its effectiveness.
      METHODS: Patient-specific VU generation was accomplished through incorporating
      CTU data into specialized software (Crusher) developed on the open access
      Visualization Tools Kit (VTK). These were then presented to fURS experts and
      novice urologists for evaluation and comparison using modified Likert-type
      questionnaire of 10-point rating scales (1 = not at all useful/not at all
      realistic/poor, 10 = very useful/very realistic/ excellent). RESULTS: Face and
      content validation of VU from 5 fURS experts in 3 different centers: overall
      usefulness 7.4 +/- 0.5, graphics 7.4 +/- 0.5, intrarenal anatomy 8.4 +/- 0.5,
      stone details 7.8 +/- 0.4, usefulness in surgical planning and training 7.6 +/-
      0.9. Significant increase of detection in the number of calyces and stones was
      found from using CTU only to CTU-VU combined in the novice group ( P = .000).
      Before VU observation, novices found much fewer calyces and stones than experts (
      P = .004 and .000, respectively). However, this gap disappeared after VU
      observation ( P = .327 and .292, respectively). VU feedback from the novices was
      superb. CONCLUSIONS: Establishing patient-specific VU through CTU data from renal
      stone patients is feasible. The present VU can significantly improve novice
      urologists' comprehension of intrarenal anatomy and stone information before fURS
      procedures. Face and content validity is also proved. This novel modality may
      serve as an important tool for fURS surgical planning, navigation, and training.

PMID- 28494642
TI  - Normal anatomy and variations in the confluence of sinuses using digital
      subtraction angiography.
AB  - OBJECTIVES: The configuration of the confluence of sinuses differs not only
      between individuals, but also between the two brain hemispheres, making the
      anatomical classification of this region difficult. In this study, we evaluated
      the anatomy of the confluence of sinuses and ascertained the accuracy and
      usefulness of digital subtraction angiography (DSA) in the evaluation of cerebral
      veins. METHODS: Bilateral carotid and vertebral artery angiographies were
      performed in 500 adult patients to evaluate the anatomy of the confluence of
      sinuses and contributory venous sinuses. We appraised the anatomy of the sinuses
      adjacent to the confluence, the lateralization of venous draining into the
      transverse sinuses (TSs), the communications between the TSs, and the
      presentation of the occipital sinus (OS). RESULTS: Based on the anatomical
      descriptions of Osborn's Brain (Diagnostic Cerebral Angiography, 2nd edition), we
      delineated 10 different configurations of the confluence of sinuses that showed
      connections among the superior sagittal sinus, the straight sinus, and the left
      and right TSs. Right side dominant transverse sinus accounted for 49% of the
      cases. Direct communication between the TSs accounted for 46.4% of the cases.
      Indirect communication accounted for 51.6% of the case, and absence of
      communication between the left and the right TS accounted for 2%. Lastly, the
      presence of OS was observed in 6% of the cases. CONCLUSION: DSA promises to be an
      effective technique for studying the anatomy and normal variations of the
      confluence of sinuses, providing useful information for the diagnosis of cerebral
      venous diseases, and ensuring safer surgical procedures.

PMID- 28494643
TI  - Randomised clinical trial of early specialist palliative care plus standard care
      versus standard care alone in patients with advanced cancer: The Danish
      Palliative Care Trial.
AB  - BACKGROUND: Beneficial effects of early palliative care have been found in
      advanced cancer, but the evidence is not unequivocal. AIM: To investigate the
      effect of early specialist palliative care among advanced cancer patients
      identified in oncology departments. SETTING/PARTICIPANTS: The Danish Palliative
      Care Trial (DanPaCT) (ClinicalTrials.gov NCT01348048) is a multicentre randomised
      clinical trial comparing early referral to a specialist palliative care team plus
      standard care versus standard care alone. The planned sample size was 300. At
      five oncology departments, consecutive patients with advanced cancer were
      screened for palliative needs. Patients with scores exceeding a predefined
      threshold for problems with physical, emotional or role function, or
      nausea/vomiting, pain, dyspnoea or lack of appetite according to the European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC QLQ-C30) were eligible. The primary outcome was the change in each
      patient's primary need (the most severe of the seven QLQ-C30 scales) at 3- and 8
      week follow-up (0-100 scale). Five sensitivity analyses were conducted. Secondary
      outcomes were change in the seven QLQ-C30 scales and survival. RESULTS: Totally
      145 patients were randomised to early specialist palliative care versus 152 to
      standard care. Early specialist palliative care showed no effect on the primary
      outcome of change in primary need (-4.9 points (95% confidence interval -11.3 to
      +1.5 points); p = 0.14). The sensitivity analyses showed similar results.
      Analyses of the secondary outcomes, including survival, also showed no
      differences, maybe with the exception of nausea/vomiting where early specialist
      palliative care might have had a beneficial effect. CONCLUSION: We did not
      observe beneficial or harmful effects of early specialist palliative care, but
      important beneficial effects cannot be excluded.

PMID- 28494644
TI  - The Alpha 7 Nicotinic Acetylcholine Receptor of Deciduous Dental Pulp Stem Cells
      Regulates Osteoclastogenesis During Physiological Root Resorption.
AB  - The physiological root resorption of deciduous teeth is a normal phenomenon, but
      the mechanisms underlying this process are still unclear. In this study,
      deciduous dental pulp stem cells (DDPSCs) and permanent dental pulp stem cells
      (DPSCs) were derived from deciduous teeth and normal permanent teeth at different
      stages of resorption. In the middle stage of root resorption, DDPSCs exhibited an
      increase in the ability to induce osteoclast differentiation. Activation of the
      alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) by secretory mammalian Ly
      6 urokinase-type plasminogen activator receptor-associated protein 1 (SLURP-1)
      caused a significant increase in the expression levels of NF-kappaB, receptor
      activator of nuclear factor-kappa B ligand (RANKL), and the ratio of
      RANKL/osteoprotegerin (OPG). These effects were inhibited by alpha-bungarotoxin
      (alpha-BTX). Furthermore, the expression levels of RANKL/OPG were significantly
      reduced following inhibition of NF-kappaB. High-strength, dynamic positive
      pressure increased the expression of SLURP-1 and alpha7 nAChR in DDPSCs in the
      stable stage. These data indicated that mechanical stress stimulated the
      expression of SLURP-1 and alpha7 nAChR in DDPSCs. Additionally, SLURP-1 activated
      alpha7 nAChR, thereby upregulating the expression of NF-kappaB and enhancing its
      activity, thus regulating RANKL/OPG expression and affecting the ability of
      DDPSCs to influence osteoclastogenesis, which likely enhances root resorption and
      leads to the physiological loss of deciduous teeth.

PMID- 28494645
TI  - Whistle-blowing process in healthcare: From suspicion to action.
AB  - BACKGROUND: Whistle-blowing is an ethical activity that tries to end wrongdoing.
      Wrongdoing in healthcare varies from inappropriate behaviour to illegal action.
      Whistle-blowing can have negative consequences for the whistle-blower, often in
      the form of bullying or retribution. Despite the wrongdoing and negative tone of
      whistle-blowing, there is limited literature exploring them in healthcare.
      OBJECTIVE: The aim was to describe possible wrongdoing in Finnish healthcare and
      to examine whistle-blowing processes described on the basis of the existing
      literature in healthcare as perceived by healthcare professionals. RESEARCH
      DESIGN: The study was a cross-sectional descriptive survey. The data were
      collected using the electronic questionnaire Whistle-blowing in Health Care and
      analysed statistically. Participants and research context: A total of 397 Finnish
      healthcare professionals participated, 278 of whom had either suspected or
      observed wrongdoing in healthcare, which established the data for this article.
      Ethical considerations: Ethical approval was obtained from the Ethics Committee
      of the University (20/2015). Permission to conduct the study was received
      according to the organisation's policies. FINDINGS: Wrongdoing occurs in
      healthcare, as 96% of the participants had suspected and 94% had observed
      wrongdoing. Regarding the frequency, wrongdoing was suspected (57%) and observed
      (52%) more than once a month. Organisation-related wrongdoing was the most common
      type of wrongdoing (suspected 70%, observed 66%). In total, two whistle-blowing
      processes were confirmed in healthcare: (1) from suspicion to consequences
      occurred to 27%, and (2) from observation to consequences occurred to 37% of the
      participants. DISCUSSION AND CONCLUSION: Wrongdoing occurs in healthcare quite
      frequently. Whistle-blowing processes were described based on the existing
      literature, but two separate processes were confirmed by the empirical data. More
      research is needed on wrongdoing and whistle-blowing on it in healthcare.

PMID- 28494646
TI  - A Randomized Study Comparing Stem Cell Transplantation Versus Conventional
      Therapy for Low- and Intermediate-Risk Myelodysplastic Syndromes Patients.
AB  - The treatment of myelodysplastic syndromes (MDS) involves improving patient
      survival and quality of life (QoL) and decreasing the likelihood of progression
      to AML. Although the treatment outcomes of MDS remain unsatisfactory, few
      comparative studies have been performed while comparing the outcomes of low-risk
      and intermediate-risk patients treated with supportive care and chemotherapeutics
      to those of patients treated with allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). Therefore, we designed a clinical control study to
      compare the outcomes of supportive care and chemotherapeutics versus allo-HSCT
      treatment in MDS patients. A total of 182 patients with MDS were enrolled in the
      study, including 91 in the no-HSCT (control) group and 91 in the allo-HSCT group.
      The complete remission (CR) rate in the allo-HSCT group was significantly higher
      than that in the control group (53.8% vs. 33.0%; P < 0.05). The QoL of patients
      in the HSCT group was much higher than that in the control group (53.8% vs.
      37.4%; P < 0.05). The overall survival (OS) rates were 79.0% and 56.0% (P < 0.05)
      in the HSCT group and the control group, respectively. In conclusion, a high-dose
      fludarabine (Flu), busulfan (Bu), cyclophosphamide (CTX)-based conditioning
      regimen was well tolerated and significantly speeded hematopoietic recovery. In
      addition, this regimen increased procedure-related toxicity and improved QoL and
      OS.

PMID- 28494647
TI  - Which dimensions of impulsivity are related to problematic practice of physical
      exercise?
AB  - Background and aims Problematic practice of physical exercise (PPPE) has been
      suggested to be a behavioral addiction. Impulsivity represents a core dimension
      of behavioral addictions. However, little is known about impulsivity facets in
      PPPE. The aim of this study was to investigate the role of impulsivity facets in
      PPPE. Methods A total of 684 students (between 18 and 25 years) took part in this
      study and filled up a battery of questionnaire, which consisted of following
      measures - Global Physical Activity Questionnaire, Exercise Dependence Scale -
      Revised, and the UPPS Impulsive Behavior Scale. Multiple regression analyses were
      utilized to investigate the predictive role of each impulsivity facet in PPPE.
      Results Age, the total level of physical activity per day, sex (male), negative
      urgency, and sensation seeking were found to be significant predictors of PPPE. A
      categorical analysis of PPPE revealed that negative urgency, positive urgency,
      and sensation seeking were significantly higher in the dependent category of
      PPPE. Discussion and conclusions Associations to negative urgency and sensation
      seeking might indicate that PPPE serves to regulate or alleviate negative affect
      or aversive emotional states. Thus, PPPE could be conceptualized as a short-term
      coping strategy dedicated to relieving negative affective states, like other
      maladaptive behaviors such as binge eating, binge drinking, or compulsive buying.

PMID- 28494648
TI  - Social networking addiction, attachment style, and validation of the Italian
      version of the Bergen Social Media Addiction Scale.
AB  - Aim Research into social networking addiction has greatly increased over the last
      decade. However, the number of validated instruments assessing addiction to
      social networking sites (SNSs) remains few, and none have been validated in the
      Italian language. Consequently, this study tested the psychometric properties of
      the Italian version of the Bergen Social Media Addiction Scale (BSMAS), as well
      as providing empirical data concerning the relationship between attachment styles
      and SNS addiction. Methods A total of 769 participants were recruited to this
      study. Confirmatory factor analysis (CFA) and multigroup analyses were applied to
      assess construct validity of the Italian version of the BSMAS. Reliability
      analyses comprised the average variance extracted, the standard error of
      measurement, and the factor determinacy coefficient. Results Indices obtained
      from the CFA showed the Italian version of the BSMAS to have an excellent fit of
      the model to the data, thus confirming the single-factor structure of the
      instrument. Measurement invariance was established at configural, metric, and
      strict invariances across age groups, and at configural and metric levels across
      gender groups. Internal consistency was supported by several indicators. In
      addition, the theoretical associations between SNS addiction and attachment
      styles were generally supported. Conclusion This study provides evidence that the
      Italian version of the BSMAS is a psychometrically robust tool that can be used
      in future Italian research into social networking addiction.

PMID- 28494649
TI  - Herbicidal activity of pure compound isolated from rhizosphere inhabiting
      Aspergillus flavus.
AB  - In the quest for bioactive natural products of fungal origin, Aspergillus flavus
      was isolated from rhizosphere of Mentha piperita using Potato Dextrose Agar (PDA)
      and Czapec Yeast Broth (CYB) nutrient media for metabolites production. In total,
      three different metabolites were purified using HPLC/LCMS and the structures were
      established using 500 Varian NMR experiments. Further the isolated metabolites in
      different concentrations (10, 100, 1000 MUg/mL) were tested for herbicidal
      activity using Completely Randomized design (CRD) against the seeds of Silybum
      marianum and Avena fatua which are major threats to wheat crop in Pakistan. Among
      the isolated metabolites, one compound was found active against the test weed
      species whose activity is reported in the present work. The chemical name of the
      compound is 2-(1, 4-dihydroxybutan-2-yl)-1, 3-dihydroxy-6, 8-dimethoxyanthracene
      9, 10(4aH, 9aH)-dione with mass of 388. Results showed that all seeds germinated
      in control treatment; however, with the metabolite treated, the growth was
      retarded to different levels in all parts of the weeds. At a dose of 1000 MUg/mL
      of the pure compound, 100% seeds of S. marianum and 60% seeds of A. fatua were
      inhibited. Interestingly, the pure compound exhibited less inhibition of 10%
      towards the seeds of common wheat (Triticum aestivum).

PMID- 28494650
TI  - Spinal metastatic lung adenocarcinoma with dural invasion and concomitant
      intradural and extradural components: a case report.
AB  - We report the case of a metastatic lung carcinoma that had metastasized to the
      thoracic extradural space and penetrated the dura, resulting in a combined extra
      and intradural spinal tumour. To our knowledge this is the first such report of a
      metastatic lung adenocarcinoma demonstrating direct dural invasion.

PMID- 28494651
TI  - Isolation and structure elucidation of a new compound from the fungus Aspergillus
      flavipes PJ03-11.
AB  - A new diphenyl ether 3-methylpentyl-2, 4-dichloroasterrate (2), along with a
      known diphenyl ether butyl 2, 4-dichloroasterrate (1) were isolated from the
      metabolites of a wetland fungus Aspergillus flavipes. PJ03-11. The structures of
      1 and 2 were determined by extensive NMR and HR-ESI-MS experiments. Compounds 1
      and 2 showed weak cytotoxic activity, but both of them showed no antimicrobial
      activity.

PMID- 28494652
TI  - The Keap1-Nrf2 Stress Response Pathway Promotes Mitochondrial Hyperfusion Through
      Degradation of the Mitochondrial Fission Protein Drp1.
AB  - AIMS: Mitochondrial function is coupled to metabolic and survival pathways
      through both direct signaling cascades and dynamic changes in mitochondrial
      morphology. For example, a hyperfused mitochondrial reticulum is activated upon
      cellular stress and is protective against cell death. As part of a genome-wide
      small inhibitory ribonucleic acid screen, we identified the central redox
      regulator, Keap1, as a novel regulator of mitochondrial morphology. Here, we
      aimed to determine the mechanism through which redox signaling and Keap1 mediate
      changes in mitochondrial morphology. RESULTS: We found that the Nrf2
      transcription factor is required for mitochondrial hyperfusion induced by
      knockdown of Keap1. Nrf2, which is negatively regulated by Keap1, mediates the
      cell's response to stress by controlling the expression of several hundred genes,
      including proteasome expression. We next showed that increased proteasome
      activity, a result of increased Nrf2 activity, is responsible for the degradation
      of the mitochondrial fission protein Drp1, which occurs in an ubiquitin
      independent manner. INNOVATION: Our study described a novel pathway by which Nrf2
      activation, known to occur in response to increased oxidative stress, decreases
      mitochondrial fission and contributes to a hyperfused mitochondrial network.
      CONCLUSION: This study has identified the Keap1-Nrf2 nexus and modulation of
      proteasomal activity as novel avenues to inhibit mitochondrial fission. These
      findings are important, because inhibiting mitochondrial fission is a promising
      therapeutic approach to restore the balance between fission and fusion, which is
      attractive for an increasing number of disorders linked to mitochondrial
      dysfunction. Antioxid. Redox Signal. 27, 1447-1459.

PMID- 28494653
TI  - Patterns and Yearly Time Trends in the Use of Radiation Therapy During the Last
      30 Days of Life Among Patients With Metastatic Rectal Cancer in the United States
      From 2004 to 2012.
AB  - PURPOSE: Although radiation therapy (RT) can provide palliative benefits for
      patients with metastatic rectal cancer, its role at the end of life remains
      unclear. The objective of this study was to assess sociodemographic and clinical
      factors associated with the use of RT during the last 30 days of life and to
      evaluate yearly time trends in RT utilization among stage IV patients with rectal
      cancer. METHODS: The 2004 to 2012 National Cancer DataBase was queried for
      patients with metastatic rectal cancer who had a documented death during follow
      up. A Bayesian multilevel logistic regression model was used to characterize
      predictive factors and yearly time trends associated with RT use in the last 30
      days of life. RESULTS: Among 10 431 patients who met inclusion criteria, 345 (3%)
      received RT during the last 30 days of life. Factors independently associated
      with RT use included older age, female sex, African American race, nonprivate
      insurance, higher comorbidity burden, and worse grade. The odds of RT use at the
      end of life decreased by 28% between 2007 and 2009 (odds ratio [OR] = 0.72, 95%
      Credible Interval (CI) = 0.58-0.93), but then increased by 16% from 2010 to 2012
      (OR = 1.16, 95% CI = 1.13-1.33), relative to 2004 to 2006. CONCLUSION: Radiation
      therapy use for patients with metastatic rectal cancer is beneficial, and efforts
      to optimize its appropriate use are important. Several factors associated with RT
      use during the last 30 days of life included disparities in sociodemographic and
      clinical subgroups. Research is needed to understand the underlying causes of
      these inequalities and the role of predictive models in clinical decision-making.

PMID- 28494654
TI  - New formulations of tacrolimus and prevention of acute and chronic rejections in
      adult kidney-transplant recipients.
AB  - : Introduction: As tolerance is not yet achievable, the kidney-transplanted
      patients have to take on a daily-basis immunosuppressive drugs in order to avoid
      acute rejection-AR-. The cornerstone of immunosuppression relies on tacrolimus
      therapy which is potentially nephrotoxic. Areas Covered: We identified from the
      studies published in the recent years those who were reporting on AR in de novo
      kidney-transplant recipients under tacrolimus-based therapy, as well as those who
      reported on the attempt to minimize tacrolimus-therapy. RESULTS: There are many
      formulations of tacrolimus: immediate-release (Prograf(r)), slow-release
      (Advagraf(r)), or extended-release (Envarsus(r)). All demonstrate a very good
      efficacy in preventing AR episodes. Studies in which tacrolimus was minimized or
      even weaned-off have shown that it was unsafe, i.e. in resulting in AR episode
      and/or de novo donor-specific alloantibodies. Recent data show that Tacrobell(r),
      a generic of tacrolimus, was as efficient as Prograf(r) in the short- and long
      term. Expert-opinion: Tacrolimus-based immunosuppression is very effective in
      preventing rejection in kidney-transplant recipients. It might be associated with
      nephrotoxicity, that can be reduced by avoiding tacrolimus trough levels too high
      in the long-term. Conversely, tacrolimus ultraminimization should not be
      attempted.

PMID- 28494656
TI  - In-Service Training for Increasing Teachers' ADHD Knowledge and Self-Efficacy.
AB  - OBJECTIVE: The aim of this article is to evaluate the efficacy of a brief in
      service training workshop at increasing primary school teachers' ADHD knowledge
      and sense of self-efficacy. METHOD: Teachers from 10 schools participated in the
      study ( n = 274) and were allocated into either an intervention or waitlist
      control group. Teachers' ADHD knowledge and self-efficacy were assessed following
      the provision of a brief training workshop on ADHD. Knowledge and self-efficacy
      retention were also assessed at a 1-month follow-up. RESULTS: Within the
      intervention group, ADHD knowledge and self-efficacy increased following the
      intervention (both ps < .001). Knowledge increased more than twofold, from very
      low to high levels, although increases in self-efficacy were more modest. Both
      knowledge and self-efficacy decreased at the 1-month follow-up but, nevertheless,
      remained higher than baseline levels ( p < .001). CONCLUSION: Results demonstrate
      that a brief training workshop can increase primary school teachers' ADHD
      knowledge and self-efficacy. Whilst increases in self-efficacy were modest, our
      findings suggest that a brief professional development intervention can be
      utilized to greatly increase teachers' ADHD knowledge, providing a cost
      effective, practical solution to address this well-evidenced gap in teachers'
      training and knowledge about the disorder.

PMID- 28494657
TI  - Ward sister in Swansea is RCNi Nurse of the Year.
AB  - The ultimate prize at the 2017 RCNi Nurse Awards has gone to Melanie Davies for
      her work championing the wellbeing of people with learning disabilities.

PMID- 28494658
TI  - 'Be honest with yourself'.
AB  - What is your job? I am trainee consultant practitioner emergency care at Health
      Education England in Wessex. The three-year consultant practitioner development
      programme prepares practitioners for consultant practice. It provides high-level
      training and mentoring across professional leadership, education, service
      development and expert clinical practice. It also combines academic study with
      clinical placements in different settings and trusts.

PMID- 28494660
TI  - Young people's changing demands for emergency services.
AB  - A ten-year study has highlighted some eye-opening statistics concerning children
      and emergency care: significantly more children are now being admitted for
      jaundice, acute bronchitis, acute and chronic tonsillitis, and viral infections.

PMID- 28494661
TI  - Duty of care has never been more relevant.
AB  - The recent attack on Westminster Bridge in London sparked an immediate response
      from the emergency services who tried to save the lives of the many people who
      had been mowed down by a single perpetrator. The emergency teams should be
      commended for their work during such an extreme and difficult situation.

PMID- 28494662
TI  - Make your vote count at the general election.
AB  - Before any general election the NHS is an important subject of every manifesto,
      where each party sets out the aims - some may say promises - that it will follow
      if it is elected: its 'big sell'.

PMID- 28494663
TI  - What is person-centred care and can it be achieved in emergency departments?
AB  - Contemporary nursing in all disciplines focuses on the concept of person-centred
      care, and how this improves patients' experiences. This article defines person
      centred care, and considers whether it can be upheld in emergency departments,
      which are facing unprecedented pressures, and in which staff resilience and
      morale are challenged continually.

PMID- 28494664
TI  - Handwashing.
AB  - Our clinical update on new National Institute for Health and Care Excellence
      (NICE) guidance on tackling antimicrobial resistance.

PMID- 28494665
TI  - Remote clinical decision-making: a clinician's definition.
AB  - Aims Remote clinical decision-making (RCDM), commonly known as 'telephone triage'
      or 'hear and treat', describes clinicians' non-face-to-face involvement with
      patient care, and is an established strategy in UK ambulance services for
      managing increasing demand. However, there is no suitable definition of RCDM that
      fully explains the roles undertaken by clinicians in 999 hubs, or for its use as
      an ambulance quality indicator (AQI). The aim of this study, which is part of a
      larger evaluation of a new RCDM module in higher education, is to determine how
      clinicians define RCDM. Methods Three participants were asked, during semi
      structured interviews, to define RCDM. The interviews were recorded, transcribed
      and thematically analysed. Results Clinicians do not focus on outcomes when
      defining RCDM, but on the efficacy of the process and the appropriateness of the
      determined outcome. Conclusion There is no precise description of the role of
      healthcare professionals in 999 clinical hubs, but there is a need for role
      clarity, for employees and organisations. The study questions the suitability of
      the definition of hear and treat as an AQI, as it does not appear to represent
      fully the various duties undertaken by 999 clinical hub healthcare professionals.
      More research is needed to consider the definition of RCDM in all its forms.

PMID- 28494666
TI  - Unlocking the NMC code of conduct.
AB  - A new student resource, Unlocking the Code, aims to help nursing students get to
      grips with the Nursing and Midwifery Council (NMC) code of conduct.

PMID- 28494667
TI  - Meet Drew - winner in the Child Health category.
AB  - 'My goal as a nurse is to ensure that every child attending our department is
      given the best care possible. We should treat the families as if they were our
      own, and I knew we were not good enough at dealing with sepsis.'

PMID- 28494655
TI  - Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide
      Association Study of Anorexia Nervosa.
AB  - OBJECTIVE: The authors conducted a genome-wide association study of anorexia
      nervosa and calculated genetic correlations with a series of psychiatric,
      educational, and metabolic phenotypes. METHOD: Following uniform quality control
      and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case
      control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the
      authors performed standard association analysis followed by a meta-analysis
      across cohorts. Linkage disequilibrium score regression was used to calculate
      genome-wide common variant heritability (single-nucleotide polymorphism [SNP]
      based heritability [h2SNP]), partitioned heritability, and genetic correlations
      (rg) between anorexia nervosa and 159 other phenotypes. RESULTS: Results were
      obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele
      frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa
      was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based
      heritability arises from common genetic variation. The authors identified one
      genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring
      a previously reported type 1 diabetes and autoimmune disorder locus. Significant
      positive genetic correlations were observed between anorexia nervosa and
      schizophrenia, neuroticism, educational attainment, and high-density lipoprotein
      cholesterol, and significant negative genetic correlations were observed between
      anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.
      CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this
      study has uncovered the first genome-wide significant locus. Anorexia nervosa
      also has large and significant genetic correlations with both psychiatric
      phenotypes and metabolic traits. The study results encourage a
      reconceptualization of this frequently lethal disorder as one with both
      psychiatric and metabolic etiology.

PMID- 28494669
TI  - Bedside handovers 'improve rapport'.
AB  - Staff at a hospital emergency assessment unit have introduced bedside nurse
      handovers to boost interaction with patients.

PMID- 28494668
TI  - Hands-on senior clinicians 'could reduce demand'.
AB  - Having senior clinicians on hand to assess emergency department (ED) patients can
      transform patient demand, according to a new report from the Institute of
      Healthcare Management.

PMID- 28494670
TI  - Number of children being admitted rises.
AB  - Emergency department admissions for babies and young children have risen by
      almost one third in a decade, a report has found.

PMID- 28494671
TI  - More MS nurses needed to reduce waiting lists.
AB  - New analysis shows the number of emergency department admissions for people with
      multiple sclerosis (MS) continues to rise, costing the NHS millions.

PMID- 28494672
TI  - Nursing and Healthcare Research at a Glance Glasper Alan Rees Colin Nursing and
      Healthcare Research at a Glance 224pp L26.99 Wiley Blackwell 9781118778791
      1118778790 [Formula: see text].
AB  - This book could appeal to all levels of nursing researchers, academics, students
      and anyone trying to rise up the clinical research ladder.

PMID- 28494673
TI  - Law and Ethics in Nursing and Healthcare: An Introduction Avery Graham Law and
      Ethics in Nursing and Healthcare: An Introduction 392pp L26.99 Sage 9781412961745
      1412961742 [Formula: see text].
AB  - The aim of this book, now in its second edition, is to set out the main concepts
      of law and ethics in healthcare. Its content is up to date, comprehensive and
      practical, and encourages readers to seek out further resources.

PMID- 28494675
TI  - Cornstarch gel found to be an alternative for ultrasound use.
AB  - Ultrasound images produced using cornstarch-based (known as cornflour in the UK)
      gel are of similar quality to those using commercial gel, according to a study in
      Emergency Medicine Journal.

PMID- 28494674
TI  - Should nurses receive formal commendations?
AB  - On 22 March news broke that an incident had occurred at the Palace of Westminster
      in London. The Metropolitan Police, London Ambulance Service and the Helicopter
      Emergency Medical Service responded and, as details emerged, it became clear
      there had been a terrorist attack.

PMID- 28494679
TI  - First rib fracture treatment should focus on other injuries.
AB  - Management of patients with fractures of the first rib should focus on
      identifying and treating associated life-threatening injuries, says a study in
      Emergency Medicine Journal.

PMID- 28494680
TI  - End of life care in emergency departments: a review of the literature.
AB  - Providing end of life care (EOLC) in emergency departments (EDs) is challenging
      because of minimal resources, lack of staff education and outdated models of
      care. Dynamic, chaotic environments like EDs require systematic, clear and
      concise principles and goals for patient care. Death in EDs is inevitable,
      therefore staff should be equipped to provide optimal care to this vulnerable
      patient group. This article reviews the literature on the barriers to providing
      EOLC in EDs, and makes recommendations for clinical practice and further
      research. EOLC refers to care of terminally and critically ill patients in their
      final days and hours of life.

PMID- 28494681
TI  - Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.
AB  - CONTEXT: The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse
      bioactivities, but little safety data are reported. OBJECTIVE: This study
      examines the toxicological profiles of C. cajan leaf extracts. MATERIALS AND
      METHODS: The leaves were extracted by water or 90% ethanol to obtain water or
      ethanol extract (WEC or EEC). EEC was suspended in water and successively
      fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker
      compounds of the extracts were monitored by high-performance liquid
      chromatography (HPLC). Kunming mice were administered with a single maximum
      acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to
      determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity
      investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or
      6.0 g/kg doses for four weeks and observed for two weeks after dosing to
      determine toxicological symptoms, histopathology, biochemistry and haematology.
      RESULTS: Flavonoids and stilbenes in the extracts were assayed. In acute toxicity
      test, no mortality and noted alterations in weight and behavioural abnormality
      were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic
      toxicity study, no mortality and significant variances in haematological and
      biochemical parameters or organ histopathology were observed, but increased
      kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and
      reduced testes and epididymis weight in EEC-treated male rats were recorded.
      These changes returned to the level of control after recovery period. CONCLUSION:
      Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.

PMID- 28494682
TI  - Operative transvaginal hydrolaparoscopy improve ovulation rate after clomiphene
      failure in polycystic ovary syndrome.
AB  - Aim of our study was to assess the ovulation rate, with mid-luteal progesterone
      level and ultrasound follicles monitoring, in PCOS CC-resistant patients
      undergone transvaginal hydrolaparoscopy ovarian drilling. A prospective
      observational study was carried out in 123 PCOS, infertile, CC-resistant patients
      who undergone THL ovarian drilling. Each woman was evaluated by hormonal
      measurement, and ultrasound evaluation during 6 months follow-up. Progesterone
      serum levels were assessed on days 20-24 of the cycle after surgical treatment.
      Pg levels >3 ng/mL were considered as ovulation. Ovulation frequency and the
      highest mean follicular diameters during the monitoring were recorded. 117
      patients complete the study, since six patients were lost to follow-up. Mean
      follicular diameter during ovulation monitoring was 16.37 mm. Ovulation rate at
      the follow up was 64.1% one month after treatment, 79.5% after three months and
      82.9% after six months. 28 patients conceived during follow-up period. Pregnancy
      rate was 70.1%. Our study has shown that THL ovarian drilling improves ovulation
      and pregnancy rate in women with CC-resistant PCOS. We believe that this approach
      should be offered as second-line therapy at all PCOS CC-resistant women who fail
      the medical methods of ovulation induction.

PMID- 28494683
TI  - What is clearance worth? Patients' stated risk tolerance for psoriasis
      treatments.
AB  - PURPOSE: The purpose of this study was to provide quantitative evidence of
      patients' tolerance for therapeutic risks associated with psoriasis treatments
      that could offer psoriasis improvements beyond the PASI 75 benchmark. MATERIALS
      AND METHODS: We used a discrete-choice experiment in which respondents chose
      between competing psoriasis treatments characterized by benefits (i.e. reduced
      plaque severity, reduced plaque area), risks (i.e. 10-year risk of tuberculosis,
      10-year risk of death from infection), and treatment regimen. We analyzed choice
      data using random-parameters logit models for psoriasis affecting the body, face,
      or hands. RESULTS: Of 927 eligible members of the National Psoriasis Foundation
      who completed the survey, 28% were unwilling to accept any greater risk of
      treatment-related infection mortality. Among the remaining 72%, respondents were
      willing to accept higher risks of infection-related mortality associated with
      treatment to completely remove plaques covering only 1% of the body, compared to
      reducing lesions from 10 to 1% of the affected area. This finding was more
      pronounced for lesions on the face. CONCLUSIONS: Most patients placed greater
      value on eliminating even very small plaques compared to avoiding treatment
      related risks. The perceived importance of complete versus near-complete
      clearance was stronger than previously documented.

PMID- 28494684
TI  - Effectiveness of Telementoring in Surgery Compared With On-site Mentoring: A
      Systematic Review.
AB  - BACKGROUND: Mentorship is important but may not be feasible for distance
      learning. To bridge this gap, telementoring has emerged. The purpose of this
      systematic review was to evaluate the effectiveness of telementoring compared
      with on-site mentoring. METHODS: A search was done up to March 2015. Studies were
      included if they used telementoring between surgeons during a clinical encounter
      and if they compared on-site mentoring and telementoring. RESULTS: A total of 11
      studies were included. All reported no difference in complication rates, and 9
      (82%) reported similar operative times; 4 (36%) reported technical issues, which
      was 3% of the total number of cases in the 11 studies. No study reported on
      higher levels of evidence for effectiveness of telementoring as an educational
      intervention. CONCLUSION: Studies reported that telementoring is associated with
      similar complication rates and operative times compared with on-site mentoring.
      However, the level of evidence to support the effectiveness of telementoring as a
      training tool is limited. There is a need for studies that provide evidence for
      the equivalence of the effectiveness of telementoring as an educational
      intervention in comparison with on-site mentoring.

PMID- 28494685
TI  - Greek Surgeon Pavlos Ioannou's Possible Influence on William Halsted's Famous
      Radical Mastectomy.
AB  - Pavlos Ioannou performed an innovative surgical operation for breast cancer in
      Vienna University Hospital in 1861. A few years later, after his return to
      Greece, an operation performed on his closest friend's child, which led to fatal
      complications, led him to retire from surgical practice. William Halsted
      travelled to Europe in order to master European surgery, including at Vienna
      University, and about 20 years later he published his famous method for radical
      mastectomy, which appears to be identical to Ioannou's operation. This article
      debates whether Halsted studied Ioannou's method in the archives of Vienna
      University (and was encouraged by Ioannou's retirement to develop this
      technique), whether he learned about it through his peers, or whether this was
      simply a historical coincidence.

PMID- 28494688
TI  - Evolution in psoriasis management.

PMID- 28494686
TI  - Clinical pharmacology, efficacy, and safety of selexipag for the treatment of
      pulmonary arterial hypertension.
AB  - INTRODUCTION: Selexipag is the first oral, non-prostanoid, selective prostacyclin
      receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary
      arterial hypertension (PAH) in adult patients. Areas covered: This article
      reviews the clinical pharmacology, efficacy, and safety of selexipag in the
      treatment of PAH. Expert opinion: Selexipag is the first oral drug that
      selectively targets the prostacyclin pathway, and has evidence of long-term
      efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH
      patients, selexipag significantly reduced the risk of the primary composite
      outcome of morbidity/mortality (M/M). The adverse events in the selexipag group
      were consistent with the known side effects of prostacyclin, including headache,
      nausea, jaw pain, and diarrhea. Importantly, selexipag was efficacious and safe
      irrespective of whether or not patients were already receiving other PAH
      therapies. With selexipag approval, triple oral combination therapy addressing
      three important pathways is available for patients with PAH. Selexipag has one
      major metabolite, ACT-333679, which is also a selective IP receptor agonist, with
      37-fold higher potency than selexipag. Pharmacokinetic properties of ACT-333679
      permit twice-daily dosing of selexipag, providing a more convenient treatment
      compared to prostacyclin or its analogs. For patients with moderate hepatic
      impairment a once-daily regimen is recommended.

PMID- 28494690
TI  - Acrylamide in thermal-processed carbohydrate-rich foods from Chinese market.
AB  - Acrylamide content in food market in China was determined with the goal to
      evaluate related health concern. In this survey, products of rice, potato corn,
      wheat as well as dried fruit slices and instant foods were analysed. All these
      types of thermal-processed carbohydrate-rich foods were frequently consumed in
      China. They were purchased from markets in Zhejiang province and analysed using a
      liquid chromatography tandem/mass spectrometry method. Acrylamide was detected in
      94.3% of 105 investigated samples, ranging from 10 to 3649 MUg/kg with an average
      value of 231 MUg/kg and a median of 114 MUg/kg. In this study, high levels were
      found in potato products (564 +/- 285 MUg/kg), corn products (524 +/- 187 MUg/kg)
      and instant foods (180 +/- 35 MUg/kg) while low levels were measured in rice
      products (82 +/- 17 MUg/kg), wheat products (96 +/- 29 MUg/kg) and dried fruit
      slices (83 +/- 13 MUg/kg).

PMID- 28494691
TI  - Central poststroke pain: A systematic review.
AB  - Background Physical, psychological, and/or social impairment can result after a
      stroke and can be exacerbated by pain. One type of pain after stroke, central
      poststroke pain, is believed to be due to primary central nervous system
      mechanisms. Estimated prevalence of central poststroke pain ranges widely from 8%
      to 55% of stroke patients, suggesting a difficulty in reliably, accurately, and
      consistently identifying central poststroke pain. This may be due to the absence
      of a generally accepted definition. Aim We aimed to clarify the role of thalamic
      strokes and damage to the spinothalamic pathway in central poststroke pain
      patients. Also, we aimed to gain a current understanding of anatomic substrates,
      brain imaging, and treatment of central poststroke pain. Summary of review Two
      independent reviewers identified 10,144 publications. Based on Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we extracted
      data from 23 papers and categorized the articles' aims into four sections:
      somatosensory deficits, pathway stimulation, clinical trials, and brain imaging.
      Conclusions Our systematic review suggests that damage to the spinothalamic
      pathway is associated with central poststroke pain and this link could provide
      insights into mechanisms and treatment. Moreover, historical connection of
      strokes in the thalamic region of the brain and central poststroke pain should be
      reevaluated as many studies noted that strokes in other regions of the brain have
      high occurrence of central poststroke pain as well.

PMID- 28494693
TI  - Keeping up with stroke meetings from around the world.

PMID- 28494692
TI  - Capsular warning syndrome as a manifestation of isolated middle cerebral artery
      dissection in a Latin American patient.

PMID- 28494694
TI  - Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or
      intracranial hemorrhage in Germany - A national case collection.
AB  - Background Idarucizumab is a monoclonal antibody fragment with high affinity for
      dabigatran that reverses its anticoagulant effects within minutes. It may exhibit
      the potential for patients under dabigatran therapy suffering ischemic stroke to
      regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in
      patients with intracerebral hemorrhage on dabigatran. Aims To provide insights
      into the clinical use of idarucizumab in patients under effective dabigatran
      anticoagulation presenting with signs of ischemic stroke or intracranial
      hemorrhage. Methods Retrospective data collected from German
      neurological/neurosurgical departments administering idarucizumab following
      product launch from January to August 2016 were used. Results Thirty-one patients
      presenting with signs of stroke received idarucizumab in 22 stroke centers.
      Nineteen patients treated with dabigatran presented with ischemic stroke and 12
      patients suffered from intracranial bleeding. In patients receiving rt-PA
      thrombolysis following idarucizumab, 79% benefitted from i.v. thrombolysis with a
      median improvement of five points in NIHSS. No bleeding complications occurred.
      Hematoma growth was observed in 2 out of 12 patients with intracranial
      hemorrhage. The outcome was favorable with a median NIHSS improvement of 5.5
      points and mRS 0-3 in 67%. Overall, mortality was low with 6.5% (one patient in
      each group). Conclusion Administration of rt-PA after reversing dabigatran
      activity with idarucizumab in case of ischemic stroke is feasible, easy to
      manage, effective, and appears to be safe. In dabigatran-associated intracranial
      hemorrhage, idarucizumab has the potential to prevent hematoma growth and improve
      outcome. Idarucizumab represents a new therapeutic option for patients under
      dabigatran treatment presenting with ischemic stroke or intracranial hemorrhage.

PMID- 28494696
TI  - Oxidative injuries induced by maternal low-protein diet in female brainstem.
AB  - Many studies have shown that a maternal low-protein diet increases the
      susceptibility of offspring to cardiovascular disease in later-life. Moreover, a
      lower incidence of cardiovascular disease in females than in males is understood
      to be largely due to the protective effect of high levels of estrogens throughout
      a woman's reproductive life. However, to our knowledge, the role of estradiol in
      moderating the later-life susceptibility of offspring of nutrient-deprived
      mothers to cardiovascular disease is not fully understood. The present study is
      aimed at investigating whether oxidative stress in the brainstem caused by a
      maternal low-protein diet administered during a critical period of fetal/neonatal
      brain development (i.e during gestation and lactation) is affected by estradiol
      levels. Female Wistar rat offspring were divided into four groups according to
      their mothers' diets and to the serum estradiol levels of the offspring at the
      time of testing: (1) 22 days of age/control diet: (2) 22 days of age/low-protein
      diet; (3) 122 days of age/control diet: (4) 122 days of age/low-protein diet.
      Undernutrition in the context of low serum estradiol compared to undernutrition
      in a higher estradiol context resulted in increased levels of oxidative stress
      biomarkers and a reduction in enzymatic and non-enzymatic antioxidant defenses.
      Total global oxy-score showed oxidative damage in 22-day-old rats whose mothers
      had received a low-protein diet. In the 122-day-old group, we observed a decrease
      in oxidative stress biomarkers, increased enzymatic antioxidant activity, and a
      positive oxy-score when compared to control. We conclude from these results that
      following a protein deficiency in the maternal diet during early development of
      the offspring, estrogens present at high levels at reproductive age may confer
      resistance to the oxidative damage in the brainstem that is very apparent in pre
      pubertal rats.

PMID- 28494697
TI  - Talking Circles to Improve Diabetes Self-care Management.
AB  - Purpose The purpose of this study was to determine if the use of both the Talking
      Circles (TCs) and diabetes self-management education (DSME) results in better
      adherence and outcomes for diabetes self-management than DSME alone in American
      Indians (AIs) with type 2 diabetes mellitus (T2DM). Methods A quasiexperimental,
      mixed-methods approach was used for AIs with uncontrolled T2DM, defined by an A1C
      > 7.0%. The experimental group (n = 20) participated in a TC and received DSME.
      The control group (n = 19) received only DSME. Talking Circles were audio-taped
      and analyzed qualitatively. Quantitative data were analyzed using the generalized
      estimating equation and Fisher exact test for all study participants every 3
      months for 1 year. Results Themes identified by TC participants were
      spirituality, gratitude, and sharing. Major topics of discussion were the
      experiences of living with T2DM, including challenges and coping. Evidence of
      positive trends for the experimental group who received the TC intervention
      included lower systolic blood pressure, lower A1C, lower weight over time, and
      increased adherence without incentives. Conclusion Talking Circles may have
      utility in improving adherence in AI adults with uncontrolled T2DM. Further
      studies are warranted, including extending the use of the TCs after completion of
      DSME sessions.

PMID- 28494695
TI  - The Role of Integrin alpha6 (CD49f) in Stem Cells: More than a Conserved
      Biomarker.
AB  - Stem cells have the capacity for self-renewal and differentiation into
      specialized cells that form and repopulated all tissues and organs, from
      conception to adult life. Depending on their capacity for differentiation, stem
      cells are classified as totipotent (ie, zygote), pluripotent (ie, embryonic stem
      cells), multipotent (ie, neuronal stem cells, hematopoietic stem cells,
      epithelial stem cells, etc.), and unipotent (ie, spermatogonial stem cells).
      Adult or tissue-specific stem cells reside in specific niches located in, or
      nearby, their organ or tissue of origin. There, they have microenvironmental
      support to remain quiescent, to proliferate as undifferentiated cells (self
      renewal), and to differentiate into progenitors or terminally differentiated
      cells that migrate from the niche to perform specialized functions. The presence
      of proteins at the cell surface is often used to identify, classify, and isolate
      stem cells. Among the diverse groups of cell surface proteins used for these
      purposes, integrin alpha6, also known as CD49f, may be the only biomarker
      commonly found in more than 30 different populations of stem cells, including
      some cancer stem cells. This broad expression among stem cell populations
      indicates that integrin alpha6 may play an important and conserved role in stem
      cell biology, which is reaffirmed by recent demonstrations of its role
      maintaining self-renewal of pluripotent stem cells and breast and glioblastoma
      cancer stem cells. Therefore, this review intends to highlight and synthesize new
      findings on the importance of integrin alpha6 in stem cell biology.

PMID- 28494698
TI  - Extemporaneously preparative biodegradable injectable polymer systems exhibiting
      temperature-responsive irreversible gelation.
AB  - On clinical application of biodegradable injectable polymer (IP) systems, quick
      extemporaneous preparation of IP formulations and longer duration time gel state
      after injection into the body are the important targets to be developed.
      Previously, we had reported temperature-responsive covalent gelation systems via
      bio-orthogonal thiol-ene reaction by 'mixing strategy' of amphiphilic
      biodegradable tri-block copolymer (tri-PCG) attaching acryloyl groups on both
      termini (tri-PCG-Acryl) with reactive polythiol. In other previous works, we
      found 'freeze-dry with PEG/dispersion' method as quick extemporaneous preparation
      method of biodegradable IP formulations. In this study, we applied this quick
      preparative method to the temperature-triggered covalent gelation system. The
      instant formulation (D-sample) could be prepared by 'freeze-dry with
      PEG/dispersion' just mixing of tri-PCG-Acryl micelle dispersion and tri-PCG/DPMP
      micelle dispersion with PEG, that can be prepared in 30 s from the dried samples.
      The obtained D-sample showed irreversible gelation and long duration time of gel
      state, which was basically the same as the formulations prepared by the usual
      heating dissolution method (S-sample). Interestingly, the D-sample could maintain
      its sol state for a longer time (24 h) after preparing the formulation at r.t.
      compared with the S-sample, which became a gel in 3 h after preparing. The IP
      system showed good biocompatibility and long duration time of the gel state after
      subcutaneous implantation. These characteristics of D-samples, quick
      extemporaneous preparation and high stability in the sol state before injection,
      would be very convenient in a clinical setting.

PMID- 28494699
TI  - Lens Capsule Perforation Without Inflammation in 4 Rabbits From Intravitreal
      Injection Studies.
AB  - Historically, it was thought that lens protein was sequestered, and injury to the
      lens capsule causing release of lens material into the eye would always result in
      ocular inflammation. Currently, it is believed that lens antigens are recognized
      as self, subject to normal T-cell tolerance. Three different single-dose
      intravitreal injection/implantation studies of 4 different test materials,
      ranging from 4 to 6 weeks in length, were performed in New Zealand White rabbits.
      The test materials included polymer microspheres, polymer rods, a solvent, and a
      hydrogel. Intravitreal injection/implantation procedures were performed on day 1,
      and indirect ophthalmoscopy and slit-lamp biomicroscopy examinations were
      performed by board-certified veterinary ophthalmologists periodically throughout
      the course of each study. None of the affected animals received corticosteroids
      or other immunomodulatory agents during the course of the studies. Four rabbits
      had perforation of the posterior lens capsule during the injection/implantation
      procedure on day 1, visible on clinical ophthalmic examination as lens capsule
      alterations described as "lens hits" and/or incipient posterior cataracts.
      Findings on slit-lamp biomicroscopy examination were limited to vitreous cells in
      2 of the animals, although not centered on the area of lens capsule disturbance.
      Histologically, there was no evidence of inflammation in association with
      extruded lens protein material in any of the affected eyes. These results
      indicate that iatrogenic damage to the lens capsule during aseptically performed
      intravitreal injections/implantations does not appear to induce inflammation in
      rabbits.

PMID- 28494700
TI  - Invasive Front Grading and Epithelial-Mesenchymal Transition in Canine Oral and
      Cutaneous Squamous Cell Carcinomas.
AB  - Oral and cutaneous tissues are the most frequent origin in canine squamous cell
      carcinoma (SSC). In SCC, changes in adhesion molecule expression and transition
      from epithelial to mesenchymal phenotype are thought to be important in
      development of invasive behavior of neoplastic cells at the leading front of the
      tumor. We therefore investigated histological invasive front grading and
      epithelial-mesenchymal transition (EMT) in both oral SCCs and cutaneous SCCs. EMT
      was assessed by evaluating immunohistochemical expression of E-cadherin, beta
      catenin, desmoglein, vimentin, and N-cadherin. Regardless of the anatomic
      location, invasive front grading resulted in higher histological grades than
      grading of the surface. Most oral SCCs were of significantly higher histologic
      grade than cutaneous SCCs ( P < .01). Expression of E-cadherin, beta-catenin, and
      desmoglein was significantly lower in oral SCC compared with cutaneous SCC ( P <
      .01). A significant association was found between invasive front grading and loss
      of E-cadherin, beta-catenin, and desmoglein ( P < .01). Also, vimentin-positive
      neoplastic cells had low immunoreactivity of these adhesion molecules, and a few
      of these neoplastic cells were positive for N-cadherin. These results suggest not
      only E-cadherin and beta-catenin but also desmoglein as markers for predicting
      biological behavior of canine SCC. Depending on their primary sites, EMT
      correlates with biological behavior and therefore histological grade of canine
      SCC. We suggest that combining invasive front grading with assessment of
      immunohistochemical expression of E-cadherin, beta-catenin, and desmoglein may
      allow more accurate prediction of biological behavior of canine SCCs.

PMID- 28494701
TI  - Spindle Cell Lipoma in Dogs.
AB  - Spindle cell lipoma (SCL) is a benign neoplasm of the adipose tissue that may
      resemble an undifferentiated soft tissue sarcoma (STS). This report describes the
      histopathological features of 6 SCLs in dogs. All SCLs were located in the
      subcutis and were composed of bland, occasionally vacuolated spindle cells
      intermixed with ropey collagen and myxoid matrix. Sudan IV stain performed in 1
      case demonstrated the lipid content of vacuoles. Mature adipocytes represented
      less than 10% of the neoplasm in 3 cases and were absent in the remaining 3.
      Average mitotic count in 10 high-power fields was 0.17. Neoplastic cells were
      immunohistochemically positive for vimentin and negative for S100 protein, smooth
      muscle actin, factor VIII-ra, and MDM2. Awareness of SCL and its specific
      histopathological features is essential to diagnose this specific tumor. Further
      studies are needed to document the biological behavior of these tumors in dogs.

PMID- 28494702
TI  - An Australian Newcastle Disease Virus With a Virulent Fusion Protein Cleavage
      Site Produces Minimal Pathogenicity in Chickens.
AB  - Newcastle disease is an important disease of poultry caused by virulent strains
      of Newcastle disease virus (NDV). During the 1998 to 2002 outbreaks of Newcastle
      disease in Australia, it was observed that the mild clinical signs seen in some
      chickens infected with NDV did not correlate with the viruses' virulent fusion
      protein cleavage site motifs or standard pathogenicity indices. The pathogenicity
      of 2 Australian NDV isolates was evaluated in experimentally challenged chickens
      based on clinical evaluation, histopathology, immunohistochemistry, and molecular
      techniques. One of these virus isolates, Meredith/02, was shown to induce only
      very mild clinical signs with no mortalities in an experimental setting, in
      contrast to the velogenic Herts 33/56 and Texas GB isolates. This minimal
      pathogenicity was associated with decreased virus replication and antigen
      distribution in tissues. This demonstrates that the Australian Meredith/02 NDV,
      despite possessing a virulent fusion protein cleavage site, did not display a
      velogenic phenotype.

PMID- 28494703
TI  - Globule Leukocytes and Other Mast Cells in the Mouse Intestine.
AB  - Only 2 major mast cell (MC) subtypes are commonly recognized in the mouse: the
      large connective tissue mast cells (CTMCs) and the mucosal mast cells (MMCs).
      Interepithelial mucosal inflammatory cells, most commonly identified as globule
      leukocytes (GLs), represent a third MC subtype in mice, which we term
      interepithelial mucosal mast cells (ieMMCs). This term clearly distinguishes
      ieMMCs from lamina proprial MMCs (lpMMCs) while clearly communicating their
      common MC lineage. Both lpMMCs and ieMMCs are rare in normal mouse intestinal
      mucosa, but increased numbers of ieMMCs are seen as part of type 2 immune
      responses to intestinal helminth infections and in food allergies. Interestingly,
      we found that increased ieMMCs were consistently associated with decreased
      mucosal inflammation and damage, suggesting that they might have a role in
      controlling helminth-induced immunopathology. We also found that ieMMC
      hyperplasia can develop in the absence of helminth infections, for example, in
      Treg-deficient mice, Arf null mice, some nude mice, and certain graft-vs-host
      responses. Since tuft cell hyperplasia plays a critical role in type 2 immune
      responses to intestinal helminths, we looked for (but did not find) any direct
      relationship between ieMMC and tuft cell numbers in the intestinal mucosa. Much
      remains to be learned about the differing functions of ieMMCs and lpMMCs in the
      intestinal mucosa, but an essential step in deciphering their roles in mucosal
      immune responses will be to apply immunohistochemistry methods to consistently
      and accurately identify them in tissue sections.

PMID- 28494705
TI  - Brucellosis in Endangered Hector's Dolphins (Cephalorhynchus hectori).
AB  - Brucella spp infections of marine mammals are often asymptomatic but have been
      associated with reproductive losses and deaths. Zoonotic infections originating
      from marine isolates have also been described. Hector's dolphins (Cephalorhynchus
      hectori) are an endangered species with a declining population, and the role of
      infectious disease in population dynamics is not fully understood. In this study,
      27 Hector's dolphins found dead around the New Zealand coastline between November
      2006 and October 2010 were evaluated for lesions previously associated with
      cetacean brucellosis. Tissues were examined using histological,
      immunohistochemical, and molecular (polymerase chain reaction [PCR]) techniques.
      Seven of 27 dolphins (26%) had at least 1 tissue that was positive on PCR for
      Brucella spp. Lesions consistent with brucellosis were present in 10 of 27 (37%)
      dolphins, but in 8 of these dolphins Brucella infection could not be demonstrated
      in lesional tissues. Two dolphins (7%) were diagnosed with active brucellosis: 1
      female with placentitis and metritis, and 1 stillborn male fetus. Brucella
      identified in these 2 dolphins had genetic similarity (99%) to Brucella
      pinnipedialis. The omp2a gene amplicon from the uterus of the female had 100%
      homology with ST27 genotype isolates from a human in New Zealand and a bottlenose
      dolphin of Pacific origin. The remaining 5 PCR-positive dolphins were assessed as
      having asymptomatic or latent infection. While most Brucella infections
      identified in this study appeared to be subclinical, the finding of 2 dolphins
      with reproductive disease due to Brucella infection suggests that this disease
      has the potential to affect reproductive success in this species.

PMID- 28494704
TI  - Endoscopic Cytology for the Diagnosis of Chronic Enteritis and Intestinal
      Lymphoma in Dogs.
AB  - Although cytology is a rapid diagnostic procedure in dogs, the cytologic criteria
      of endoscopic biopsies for chronic enteritis and intestinal lymphoma are not well
      defined. An immediate diagnosis using cytology would benefit patients by enabling
      prompt initiation of therapy. The objective of this study was to investigate the
      correlation between the results of endoscopic cytology and histopathology. In
      this study, 167 dogs with clinical signs of chronic gastrointestinal disease were
      included. On the basis of histopathology, the following diagnoses were
      determined: lymphocytic-plasmacytic enteritis in 93 dogs; eosinophilic enteritis
      in 5 dogs; small cell intestinal lymphoma in 45 dogs; and large cell intestinal
      lymphoma in 24 dogs. Two clinical pathologists retrospectively evaluated the
      endoscopic cytology of squash-smear preparations. The cytologic diagnoses of
      inflammation, small cell lymphoma, and large cell lymphoma were based on the
      severity of lymphocyte infiltration, the size of infiltrated lymphocytes, and
      eosinophil/mast cell infiltration. The clinical severity score was significantly
      increased along with the degree of lymphocyte infiltration evaluated by cytology.
      The cytologic diagnosis was in complete agreement with the histopathologic
      diagnosis in 136 of 167 (81.4%) cases. For the differentiation between enteritis
      and lymphoma, endoscopic cytology had a sensitivity of 98.6%, a specificity of
      73.5%, a positive predictive value of 72.3%, and a negative predictive value of
      98.6%. The log-rank test and Cox regression analysis showed that the results of
      cytology predicted the prognosis. These results suggest that endoscopic cytology
      is a useful technique to aid diagnosis of intestinal inflammation and lymphoma in
      dogs.

PMID- 28494706
TI  - Ranid Herpesvirus 3 and Proliferative Dermatitis in Free-Ranging Wild Common
      Frogs (Rana Temporaria).
AB  - Amphibian pathogens are of current interest as contributors to the global decline
      of amphibians. However, compared with chytrid fungi and ranaviruses,
      herpesviruses have received relatively little attention. Two ranid herpesviruses
      have been described: namely, Ranid herpesvirus 1 (RHV1) and Ranid herpesvirus 2
      (RHV2). This article describes the discovery and partial characterization of a
      novel virus tentatively named Ranid herpesvirus 3 (RHV3), a candidate member of
      the genus Batrachovirus in the family Alloherpesviridae. RHV3 infection in wild
      common frogs (Rana temporaria) was associated with severe multifocal epidermal
      hyperplasia, dermal edema, a minor inflammatory response, and variable mucous
      gland degeneration. Intranuclear inclusions were numerous in the affected
      epidermis together with unique extracellular aggregates of herpesvirus-like
      particles. The RHV3-associated skin disease has features similar to those of a
      condition recognized in European frogs for the last 20 years and whose cause has
      remained elusive. The genome of RHV3 shares most of the features of the
      Alloherpesviruses. The characterization of this presumptive pathogen may be of
      value for amphibian conservation and for a better understanding of the biology of
      Alloherpesviruses.

PMID- 28494707
TI  - Histologic and Ultrastructural Findings in Dogs With Chronic Respiratory Disease
      Suspected of Ciliary Dyskinesia.
AB  - Mucociliary clearance is a main defense mechanism of the respiratory tract, which
      can be inherently impaired in primary ciliary dyskinesia (PCD) or reversibly
      altered in secondary ciliary dyskinesia (SCD). Limited diagnostic test
      availability likely leads to misdiagnosis or underdiagnosis of PCD in animals.
      This study evaluated the light and transmission electron microscopy (TEM) changes
      in the respiratory mucosa of 15 dogs with chronic respiratory disease suspected
      of PCD. Necropsy was performed in 1 case and 2 dogs were used as negative
      controls. PCD was confirmed in 1 dog, which presented with chronic otitis,
      bronchopneumonia, hydrocephalus and ultrastructural abnormalities in 84% of the
      assessed cilia, including absence of dynein arms and microtubular changes. The 14
      other cases showed only nonspecific alterations, such as ciliary disorientation,
      compound cilia, ciliary edema, and axoneme bubbles in a minority of the evaluated
      cilia and were classified as SCD. Ciliary ultrastructural analysis can confirm a
      diagnosis of PCD if specific abnormalities exist. TEM remains an important
      investigational tool in veterinary medicine, as no other specific test for PCD in
      dogs has been standardized yet.

PMID- 28494708
TI  - Ovis aries Papillomavirus 3 in Ovine Cutaneous Squamous Cell Carcinoma.
AB  - Squamous cell carcinoma (SCC) is a common malignancy affecting humans and other
      animals. Papillomaviruses (PVs) are frequently reported as causal agents of
      cutaneous benign and malignant epithelial lesions in different animal species,
      but only few studies have investigated their role in ovine SCC. In this study, we
      explore the possible involvement of the Ovine aries PVs (OaPV1, OaPV2, OaPV3) in
      cutaneous SCC using an integrated histological and molecular approach. Forty
      cutaneous SCCs from different anatomical locations of Sardinian sheep and 40
      matched non-SCC samples were evaluated histologically and by polymerase chain
      reaction (PCR) to assess the presence of ovine PVs. In addition, DNA in situ
      hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR)
      were carried out to evaluate the cellular localization and viral transcriptional
      activity, respectively. OaPV3 DNA was detected in 26 of 40 (65%) SCCs and in 12
      of 40 (30%) non-SCC samples using PCR. OaPV1 and OaPV2 were not detected. OaPV3
      viral DNA was observed by ISH in malignant epithelial squamous cells of 18 of 40
      (45%) SCCs. In addition, the viral transcriptional activity was identified in 24
      of 40 (60%) SCCs by RT-PCR. Notably, a higher viral positivity was observed in
      SCCs compared with non-SCC samples. The considerable infection rate of OaPV3 in
      the most common skin tumor of the sheep suggests that PV could represent a key
      factor in the onset of ovine SCC.

PMID- 28494709
TI  - Hypervirulent Klebsiella pneumoniae in California Sea Lions ( Zalophus
      californianus): Pathologic Findings in Natural Infections.
AB  - Tissues of stranded California sea lions ( Zalophus californianus) naturally
      infected with a hyperviruluent strain of Klebsiella pneumoniae were examined by
      histopathology and immunohistochemistry against the K. pneumoniae K2 capsular
      antigen. In 7 of 8 animals, there was severe purulent bronchopneumonia, sometimes
      complicated by fibrinonecrotizing pleuritis with pyothorax. In affected areas of
      lung, large numbers of degenerate neutrophils and macrophages were admixed with
      rare large extracellular and intracellular gram-negative bacilli surrounded by a
      prominent capsule. Through serotyping, polymerase chain reaction, sequencing, and
      immunohistochemistry, these bacteria were confirmed to be a K2 serotype of K.
      pneumoniae. The same bacteria were identified through double immunolabeling
      within macrophages in blood vessels, lymph nodes, spleen, and liver. Intact K.
      pneumoniae were identified on epithelial surfaces of the nasopharyngeal,
      tracheal, and small intestine mucosae and within distal renal tubules. Our
      findings indicate that hypervirulent K. pneumoniae causes severe respiratory
      disease and intrahistiocytic bacteremia in California sea lions.

PMID- 28494711
TI  - Abstracts to be presented at the 28th Annual Scientific Sessions.

PMID- 28494712
TI  - Membership spotlight.

PMID- 28494710
TI  - 2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity
      Peripheral Artery Disease: Executive Summary.

PMID- 28494713
TI  - Vascular complications associated with transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) is now an accepted pathway for
      aortic valve replacement for patients who are at prohibitive, severe and
      intermediate risk for traditional aortic valve surgery. However, with this rising
      uptrend and adaptation of this new technology, vascular complications and their
      management remain an Achilles heel for percutaneous aortic valve replacement. The
      vascular complications are an independent predictor of mortality for patients
      undergoing TAVR. Early recognition of these complications and appropriate
      management is paramount. In this article, we review the most commonly encountered
      vascular complications associated with currently approved TAVR devices and their
      optimal percutaneous management techniques.

PMID- 28494714
TI  - Is the Hepatic Factor a miRNA that Maintains the Integrity of Pulmonary
      Microvasculature by Inhibiting the Vascular Endothelial Growth Factor?
AB  - BACKGROUND: The "hepatic factor," a molecule or group of molecules present in the
      hepatic venous blood, essential for the prevention of the development of
      pulmonary arteriovenous malformations (PAVMs) and right-to-left shunting has been
      a conceptual enigma in the understanding of many related conditions. METHODS:
      Patients with various forms of liver diseases including acute hepatic failure,
      and others with normal hepatic function like hereditary hemorrhagic
      telangiectasia (HHT), inflammatory and parasitic disorders, cardiogenic
      hepatopulmonary syndrome (cHPS) and skin disorders like Dyskeratosis congenita
      are all known to cause PAVMs. Over a period of the last two decades our
      understanding of the pathogenesis of PAVMs has changed, but the mechanisms are
      still not clearly understood. The presence of PAVMs once considered a
      contraindication for liver transplantation is now a cure for PAVMs in patients
      with HPS. RESULTS: In this article the molecular mechanisms and the underlying
      pathogenesis of PAVMs are discussed and the role of microRNA (miRNA) in its
      pathogenesis is favorably argued. Identifying and preventing or treating the
      underlying mechanisms will significantly influence the management of a large
      group of patients who at present cannot be effectively treated with a very poor
      prognosis. Progressive polycythemia, desaturation, stroke, and infection are
      serious complications of PAVMs. CONCLUSION: The clinical data and current
      understanding leads to the possible role of miRNA, which inhibits Vascular
      Endothelial Growth Factor (VEGF) synthesis as a pathogenic mechanism for the
      development of PAVMs.

PMID- 28494715
TI  - The Click Test: A Novel Tool to Quantify the Age-Related Decline of Fast Motor
      Sequencing of the Thumb.
AB  - BACKGROUND: The thumb plays a critical role for manual tasks during the
      activities of daily life and the incidence of neurological or musculoskeletal
      disorders affecting the voluntary movements of the thumb is high in the elderly.
      There is currently no tool to assess repetitive motor sequencing of the thumb
      during ageing. OBJECTIVES: To report a novel procedure (the Click Test) assessing
      the effects of ageing on fast motor sequencing of the thumb. METHOD: Healthy
      subjects (n = 252; mean age +/- SD: 49.76 +/- 19.97 years; range: 19-89 years;
      F/M: 151/101) were asked to perform fast repeated flexion/extension movements of
      the thumb using a mechanical counter. RESULTS: Motor performances (assessed by
      the number of clicks during 3 time periods: 15, 30 and 45 sec), significantly
      decreased as a function of age for both the dominant (age effect; p< 0.0001 for
      15, 30 and 45 sec) and the non-dominant hand (p<0.0001 for 15, 30 and 45 sec).
      The number of clicks was significantly higher in males (gender effect; p<0.001)
      and was higher on the dominant side as compared to the non-dominant side
      (handedness effect: p<0.001). The Click Test is characterized by high
      repeatability (coefficients of variation from 3.20 to 4.47%), excellent intra
      rater reliability (intra-class coefficients ICC ranging from 0.89 to 0.98), high
      inter-rater reproducibility (Pearson's product correlation ranging from 0.85 to
      0.96), high internal consistency (Cronbach alpha coefficient=0.95) and is highly
      correlated in terms of relative performances with the box and block test and the
      9-hole peg test (positive linear correlation with the results of the box and
      block test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non
      dominant hand; negative linear correlation with the results of the 9-hole peg
      test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant
      hand). CONCLUSION: The Click Test is an entirely novel and very low cost tool to
      reliably discriminate the ageing effects upon the performances during fast
      repetitive motor sequencing of the thumb. The potential clinical and research
      applications for motor functions are multiple, especially in acute and chronic
      neurological disorders affecting the thumb as well as in the field of
      rheumatology and orthopedics.

PMID- 28494716
TI  - Gender Medicine and Pharmacoeconomics: A Narrative Review of the International
      Literature of the Last 5 Years. A Revision of Evidences about the Relationship
      Between Gender and Economic Consumption in Health.
AB  - INTRODUCTION: The influence of patient gender on the economic impact of health
      care has increasingly been examined in the recent literature. Gender appears to
      have an impact on healthcare resource consumption, due to possible differences in
      the patient's response to a chosen therapeutic management strategy or to a
      healthcare intervention. OBJECTIVE: The present work is aimed at collecting and
      reviewing evidences about the relationship between gender and economic
      consumption in health based on worldwide scientific literature published in the
      last 5 years. METHOD: We conducted a narrative review of evidence from an initial
      pool of 904 articles, selecting information about gender-specific economic impact
      in any therapeutic area. RESULTS: After title, abstract and full text review, 111
      articles were relevant to the paper scope. The reviewed studies seem to be
      confirming that a difference exists between males and females in the economic
      implications of healthcare management and that those differences are particularly
      relevant for cardiovascular and metabolic pathologies. Preliminary evidence
      suggests overall healthcare costs are slightly higher in females than males,
      while some specific and non-quantitative items of resource consumption, such as
      quality of prescriptions, might favour male patients. Results do not allow to
      clearly claiming an overall cost shift towards males or females, since their
      polarization varies depending on the considered cost item or event category.
      CONCLUSION: Studies suggested the presence of a gender difference in overall
      healthcare resource consumption and costs. Nevertheless, these aspects still lack
      thorough examination in literature and further analyses would be required on
      longer time periods.

PMID- 28494717
TI  - Gelatin as Biomaterial for Tissue Engineering.
AB  - Tissue engineering is considered one of the most important therapeutic strategies
      of regenerative medicine. The main objective of these new technologies is the
      development of substitutes made with biomaterials that are able to heal, repair
      or regenerate injured or diseased tissues and organs. These constructs seek to
      unlock the limited ability of human tissues and organs to regenerate. In this
      review, we highlight the convenient intrinsic properties of gelatin for the
      design and development of advanced systems for tissue engineering. Gelatin is a
      natural origin protein derived from collagen hydrolysis. We outline herein a
      state of the art of gelatin-based composites in order to overcome limitations of
      this polymeric material and modulate the properties of the formulations. Control
      release of bioactive molecules, formulations with conductive properties or
      systems with improved mechanical properties can be obtained using gelatin
      composites. Many studies have found that the use of calcium phosphate ceramics
      and diverse synthetic polymers in combination with gelatin improve the mechanical
      properties of the structures. On the other hand, polyaniline and carbon-based
      nanosubstrates are interesting molecules to provide gelatin-based systems with
      conductive properties, especially for cardiac and nerve tissue engineering.
      Finally, this review provides an overview of the different types of gelatin-based
      structures including nanoparticles, microparticles, 3D scaffolds, electrospun
      nanofibers and in situ gelling formulations. Thanks to the significant progress
      that has already been made, along with others that will be achieved in a near
      future, the safe and effective clinical implementation of gelatin-based products
      is expected to accelerate and expand shortly.

PMID- 28494718
TI  - 'Osteoimmunology' Offers New Perspectives for the Treatment of Pathological Bone
      Loss.
AB  - New evidence of the interactions between the immune system and bone has
      accumulated in bone diseases, including osteoporosis, periodontitis and
      rheumatoid arthritis. A marked imbalance between bone resorption and formation is
      central to the onset of pathological bone loss. Osteoimmunology has revealed that
      the immune system, including T cells, B cells and inflammatory cytokines, is a
      key regulator of both osteoclasts and osteoblasts. Th1 cells, which differentiate
      from CD4+T cells, are thought to play a major function during bone loss.
      Moreover, the correlated expression of Th1 cytokines (interleukin-12 (IL-12),
      interferon-gamma (IFN-gamma)) and bone-resorbing cytokines (tumor necrosis factor
      alpha (TNF-alpha), IL-1) also plays a key role during inflammatory induced bone
      resorption. Furthermore, a relatively new member of the CD4+T cell family Th17
      displays the ability to promote osteoclast activity. The effect of IFN-gamma and
      IL-17 released by Th 17 cells on pre-osteoclast proliferation, differentiation
      and apoptosis provides the preliminary basis for the immune mechanism of
      pathological bone loss. The role of B cells in osteoimmunological interactions
      has long been suspected based on findings of B cells as active regulators of the
      RANK/RANKL/OPG axis. Pathological bone loss, including osteoporosis and human
      immunodeficiency virus-associated bone loss, are related to the altered RANKL/OPG
      through modified production by B cells, supporting this assumption. All of the
      above evidence may provide new theoretical explanations for the relationship
      between bone metabolism and the immune system as well as offer perspectives for
      the prevention and treatment of pathological bone loss.

PMID- 28494720
TI  - HLA-C Single Nucleotide Polymorphism Associated with Increased Viral Load Level
      in HIV-1 Infected Individuals from Northeast Brazil.
AB  - BACKGROUND: Genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon
      domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes are known to
      influence the HIV-1 replication and disease progression. OBJECTIVE AND METHOD: We
      evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321)
      and ZNRD1-AS1 (rs3869068), single nucleotide polymorphisms (SNPs) in 266 HIV-1
      infected and 223 unexposed-uninfected individuals from Northeast Brazil and their
      relation to HIV-1 infection, CD4 T cells count and viral load pre-treatment.
      RESULTS: HLA-C SNPs were in Linkage Disequilibrium (D'=0.84), constituting four
      possible haplotypes. Our results showed that HLA-C, ZNRD1 and ZNRD1-AS1 SNPs as
      well as HLA-C haplotypes frequencies were not significantly different between HIV
      1-infected and unexposed-uninfected individuals. In addition, we analyzed HLA-C
      and ZNRD-1 and ZNRD1-AS1 SNPs considering CD4+ T cell counts and viral load
      before the antiretroviral treatment. Individuals carrying HLA-C rs9264942 TT
      genotype showed a significant increased level of HIV-1 viral load pre-treatment,
      in comparison with individuals carrying the CC genotype (p-value = 0.0092).
      Finally, we stratified our findings according to CCR5Delta32 allele presence
      along with the studied SNPs: no statistically significant influence over viral
      load pre-treatment has been found. CONCLUSION: The association between HLA-C
      rs9264942 SNP and viral load prior treatment in an admixed population from North
      East Brazil was in agreement with findings from previous studies obtained on
      different ethnic groups; however more studies should be conducted in order to
      clarify how HLA-C impair the HIV-1 replication.

PMID- 28494721
TI  - m6A Modification and Implications for microRNAs.
AB  - OBJECTIVE: RNA is chemically modified with over 100 distinct reactions. Among
      these reactions, methylation is probably the most extensively studied
      modification on the RNA molecule. Studies suggest methylation of Adenine residues
      (m6A) to be widespread in the transcriptome with potentially important roles in
      biological processes. METHOD: Here, we review recent literature on m6A
      modification and potential implications for microRNA (miRNA) mediated gene
      expression regulation. These implications involve miRNA biogenesis, mRNA-miRNA
      interactions and m6A target selection. CONCLUSION: Understanding the extent and
      functions of m6A is likely to improve our understanding of the complexities of
      the transcriptome regulation in normal and in disease states.

PMID- 28494719
TI  - Levodopa in Parkinson's Disease: Current Status and Future Developments.
AB  - BACKGROUND: Ever since the pioneering reports in the 60s, L-3,4
      Dioxyphenylalanine (levodopa) has represented the gold standard for the treatment
      of Parkinson's Disease (PD). However, long-term levodopa (LD) treatment is
      frequently associated with fluctuations in motor response with serious impact on
      patient quality of life. The pharmacokinetic and pharmacodynamic properties of LD
      are pivotal to such motor fluctuations: discontinuous drug delivery, short half
      life, poor bioavailability, and narrow therapeutic window are all crucial for
      such fluctuations. During the last 60 years, several attempts have been made to
      improve LD treatment and avoid long-term complications. METHODS: Research and
      trials to improve the LD pharmacokinetic since 1960s are reviewed, summarizing
      the progressive improvements of LD treatment. RESULTS: Inhibitors of peripheral
      amino acid decarboxylase (AADC) have been introduced to achieve proper LD
      concentration in the central nervous system reducing systemic adverse events.
      Inhibitors of catechol-O-methyltransferase (COMT) increased LD half-life and
      bioavailability. Efforts are still being made to achieve a continuous
      dopaminergic stimulation, with the combination of oral LD with an AADC inhibitor
      and a COMT inhibitor, or the intra-duodenal water-based LD/ carbidopa gel.
      Further approaches to enhance LD efficacy are focused on new non-oral
      administration routes, including nasal, intra-duodenal, intrapulmonary (CVT-301)
      and subcutaneous (ND0612), as well as on novel ER formulations, including IPX066,
      which recently concluded phase III trial. CONCLUSION: New LD formulations, oral
      compounds as well as routes have been tested in the last years, with two main
      targets: achieve continuous dopaminergic stimulation and find an instant deliver
      route for LD.

PMID- 28494722
TI  - Adult Stem Cells and Hydrogels for Cartilage Regeneration.
AB  - Cartilage tissue engineering is emerging as a therapeutic approach for the repair
      and regeneration of cartilage tissue defects resulting from trauma and disease.
      It is still essential to explore approaches that employ combinations of ideal
      seed cells, biomaterials, and growth factors to repair defect areas because
      cartilage lacks spontaneous regenerative capabilities and traditional treatments
      do not fully satisfy clinical requirements. The purpose of this review is to
      summarize key advances in this area with an emphasis on adult stem cells because
      these cells possess a self-renewal ability and the potential for multi
      directional differentiation when cultured under appropriate conditions, such as
      chondrocyte differentiation to synthesize cartilage-specific matrix proteins.
      Additionally, hydrogels and their synergistic action with growth factors to co
      regulate cell behaviors and cartilage regeneration will be addressed. Hydrogels
      are three-dimensional water-swollen networks that provide a unique
      microenvironment to promote the chondrogenic phenotype by encapsulating cells as
      a functional cartilage substitute in a defect area. Ultimately, this review
      presents the prospect of combining adult stem cells, hydrogels, and growth
      factors using interdisciplinary approaches that may lead to significant
      breakthroughs in cartilage regeneration in the future.

PMID- 28494723
TI  - Recent Advances in Vaccines Against Leishmania Based on Patent Applications.
AB  - BACKGROUND: Leishmaniasis is caused by parasites of the genus Leishmania, and
      represents a group of chronic diseases with an epidemiological and clinical
      diversity. The disease is endemic in tropical regions, being found in 98
      countries, affecting around 12 million people, with an estimated increase of 1.5
      million per year. METHODS: The present review aims to analyze recent and most
      important patents regarding development of vaccines to improve immunization
      against leishmaniasis. For this purpose, the Web of Science - Derwent Innovations
      Index was consulted. There is also a short description of the licensed vaccines
      already on the market for commercialization, and a critical opinion on future
      developments. RESULTS: The data herein presented comprises national and
      international filings, thus considering the patent's country of origin, and can
      be used an indicator of a country's technological development regarding a
      specific field. Several types of vaccines against Leishmania were studied. The
      main classes comprise: vaccines using live cells (virulent or attenuated); dead
      cells; containing recombinant protein; using DNA of the parasite. United States
      (74 patents) leads the ranking of patent applications for vaccines against
      Leishmania, followed by Brazil (36 patents), which is an endemic region of
      leishmaniasis with 20,000 human cases of cutaneous leishmaniasis and over 3,000
      cases of visceral form. CONCLUSION: This review showed that there is still a lot
      of space for development regarding the creation of a feasible, effective vaccine
      against leishmaniasis. The scientific community appears to be taking steps in the
      right direction, though.

PMID- 28494724
TI  - C-type Lectin Receptor: Old Friend and New Player.
AB  - During the last two decades, C-type lectin receptors (CLRs) have been
      demonstrated to play key roles in initiating the host immune response against
      fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2,
      Dectin-3 and Mincle recognize the cell wall component from the infected
      microorganisms by using their carbohydrate recognition domain (CRD). Upon
      stimulation, CLRs induce multiple signal transduction cascades through their own
      immunereceptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM
      containing adaptor proteins such as FcRgamma, which then lead to the activation
      of nuclear factor kappa B (NF-kappaB) through Syk- and CARD9-dependent pathway.
      Dissecting CLR signal cascades and their effects on host immune cells is
      essential to understand the molecular mechanisms in regulating host antifungal
      immunity. Recently, the activated CLRs including Dectin-1 and Dectin-2 are
      reported to undergo lysome-mediated degradation by an E3 ubiquitin ligase CBL-b.
      Moreover, structural analysis will help understand the molecular mechanism of
      these CLRs and provide clues to rational design for effective anti-fungal drugs.
      Overall, we summarize the current knowledge on activating and inhibitory CLRs and
      discuss how to boost host immune system to fight against invasive fungal
      infection.

PMID- 28494725
TI  - Computational Methods for Predicting ncRNA-protein Interactions.
AB  - BACKGROUND: RNA-protein interactions (RPIs) play an important role in many
      cellular processes. In particular, noncoding RNA-protein interactions (ncRPIs)
      are involved in various gene regulations and human complex diseases. High
      throughput experiments have provided a large number of valuable information about
      ncRPIs, but these experiments are expensive and timeconsuming. Therefore, some
      computational approaches have been developed to predict ncRPIs efficiently and
      effectively. METHODS: In this work, we will describe the recent advance of
      predicting ncRPIs from the following aspects: i) the dataset construction; ii)
      the sequence and structural feature representation, and iii) the machine learning
      algorithm. RESULTS: The current methods have successfully predicted ncRPIs, but
      most of them trained and tested on the small benchmark datasets derived from
      ncRNA-protein complexes in PDB database. The generalization performance and
      robust of these existing methods need to be further improved. CONCLUSION:
      Concomitant with the large numbers of ncRPIs generated by high-throughput
      technologies, three future directions for predicting ncRPIs with machine learning
      should be paid attention. One direction is that how to effectively construct the
      negative sample set. Another is the selection of novel and effective features
      from the sequences and structures of ncRNAs and proteins. The third is the design
      of powerful predictor.

PMID- 28494726
TI  - Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma
      (NSCLC) Cells.
AB  - OBJECTIVE: Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has
      been widely used as a food supplement and reported to have antioxidant and
      anticancer properties. The current study was designed to assess the cytotoxic,
      apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water
      C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. METHODS: A549
      cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at
      various concentrations (0-300 MUg/ml) for 24 hr. The comet assay and gammaH2AX
      assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation
      of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel
      electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells.
      RESULTS: Chlorella vulgaris hot water extract induced apoptosis and DNA damage in
      human lung carcinoma cells. CONCLUSION: CGF can thus be considered a potential
      cytotoxic or genotoxic drug for treatment of lung carcinoma.

PMID- 28494727
TI  - Expression of Toll-like Receptor 2 and Toll-like Receptor 4 in Tuberculous
      Pleural Effusion.
AB  - BACKGROUND: Toll-like receptor-2 (TLR2) and Toll-like receptor-4 (TLR4) have been
      reported to play a crucial role in tuberculosis, however, little is known about
      their expression in tuberculous pleuritis. OBJECTIVE: The goal of this work is to
      explore the expressions of TLR2 and TLR4 in tuberculous pleuritis and their
      predominant expressions on cells. METHODS: Levels of soluble TLR2 and TLR4 by
      enzyme linked immunosorbent assay (ELISA) in 58 patients with tuberculous pleural
      effusion (PE) and 43 patients with malignant PE were determined. The related
      genes were analyzed by RT-PCR and the membrane expressions of TLR2 and TLR4 on
      CD3+, CD14+, and CD19+ monocytes were assessed by using flow cytometry in 20 of
      58 patients with tuberculous pleuritis. RESULTS: Our results showed that the
      levels of ADA, IL-27 and IFN-gamma in tuberculous PE were obviously higher than
      in malignant PE. Moreover, the concentrations of soluble TLR2 and soluble TLR4 in
      PE were significantly higher than those in peripheral blood of the same patients,
      as well as the levels of soluble TLR2 in tuberculous PE were significantly higher
      than those in malignant effusions. Furthermore, the levels of TLR2, TLR4 and IFN
      gamma mRNA expression were marked increased in the tuberculous PE when compared
      with the correspondent serum. Importantly, we found that the predominant
      expressions of TLR2 in monocyte were on CD19 B cells, and the predominant
      expressions of TLR4 were on CD14 monocytes/macrophages. CONCLUSION: Our findings
      provided the evidence of a role for TLRs expression in tuberculous PE.

PMID- 28494728
TI  - Design of Ru-arene Complexes for Antitumor Drugs.
AB  - Recently, a number of promising ruthenium complexes have been investigated as
      anticancer drugs. Ru-arene complexes with [(eta6-arene)Ru(X)(Y)(Z)] type, which
      exhibit a great structural variety, offer much potential in drug design. In this
      review we provide an overview of the progress in the field of arene ruthenium
      chemistry. We focus our attention particularly on the molecular structures and
      the anticancer applications of the Ru-arene complexes. Recent developments in the
      chemistry of arene ruthenium complexes will provide information for the
      investigation of novel anticancer organometallic drugs.

PMID- 28494729
TI  - Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents.
AB  - BACKGROUND: On account of significant biological activities, quinoline
      derivatives have drawn more attention to the synthesis and biological activities
      in the search for new therapeutic agents. Several new synthetic approaches have
      been implemented to derive new molecules from quinoline and all the synthesized
      molecules showed effective anticancer activity. METHOD: Some molecules are
      synthesized using quinolones as precursor reactant, which is another effective
      product of quinoline, also showing significant activity against malignant tumors.
      The presence of nitrogen in it and its ability to bind with enzymes like gyrase,
      topoisomerase II and kinase have also proven it with antitumor activity.
      CONCLUSION: This review encapsulates the recent advances in the synthesis and
      anticancer activity of Quinoline derivatives.

PMID- 28494730
TI  - Small Molecule Efflux Pump Inhibitors in Mycobacterium tuberculosis: A Rational
      Drug Design Perspective.
AB  - Drug resistance in Mycobacterium tuberculosis (M. tuberculosis) complicates
      management of tuberculosis. Efflux pumps contribute to low level resistance and
      acquisition of additional high level resistance mutations through sub-therapeutic
      concentrations of intracellular antimycobacterials. Various efflux pump
      inhibitors (EPIs) have been described for M. tuberculosis but little is known
      regarding the mechanism of efflux inhibition. As knowledge relating to the
      mechanism of action and drug target is central to the rational drug design of
      safe and sufficiently selective EPIs, this review aims to examine recent
      developments in the study of EPIs in M. tuberculosis from a rational drug
      development perspective and to provide an overview to facilitate systematic
      development of therapeutically effective EPIs. Review of literature points to a
      reduction in cellular energy or direct binding to the efflux pump as likely
      mechanisms for most EPIs described for M. tuberculosis. This review demonstrates
      that, where a direct interaction with efflux pumps is expected, both molecular
      structure and general physicochemical properties should be considered to
      accurately predict efflux pump substrates and inhibitors. Non-competitive EPIs do
      not necessarily demonstrate the same requirements as competitive inhibitors and
      it is therefore essential to differentiate between competitive and non
      competitive inhibition to accurately determine structure activity relationships
      for efflux pump inhibition. It is also evident that there are various
      similarities between inhibitors of prokaryotic and eukaryotic efflux pumps but,
      depending on the specific chemical scaffolds under investigation, it may be
      possible to design EPIs that are less prone to inhibition of human P
      glycoprotein, thereby reducing side effects and drug-drug interactions.

PMID- 28494731
TI  - Microwave Assisted Grafting of Gums and Extraction of Natural Materials.
AB  - BACKGROUND: Microwave assisted modification of polymers has become an established
      technique for modifying the functionality of polymers. Microwave irradiation
      reduces reaction time as well as the use of toxic solvents with enhanced
      sensitivity and yields of quality products. OBJECTIVE: In this review article
      instrumentation and basic principles of microwave activation have been discussed.
      Microwave assisted grafting of natural gums, characterization of grafted polymers
      and their toxicological parameters have also been listed. Pharmaceutical
      applications viz. drug release retardant, mucoahesion and tablet
      superdisintegrant potential of microwave assisted gums has also been discussed.
      CONCLUSION: An overview of microwave assisted extraction of plant based natural
      materials has also been presented.

PMID- 28494732
TI  - Pharmacokinetics of Botanical Drugs and Plant Extracts.
AB  - BACKGROUND: Botanical drugs contain plant extracts, which are complex mixtures of
      compounds. As with conventional drugs, it is necessary to validate their efficacy
      and safety through preclinical and clinical studies. However, pharmacokinetic
      studies for active constituents or characteristic markers in botanical drugs are
      rare. OBJECTIVE: The objective of this review was to investigate the global state
      of the art in pharmacokinetic studies of active ingredients present in plant
      extracts and botanical drugs. A review of pharmacokinetics studies of chemical
      constituents of plant extracts and botanical drugs was performed, with a total of
      135 studies published between January 2004 and February 2015 available in
      recognized scientific databases. Botanical preparations were mainly found in the
      form of aqueous extracts of roots and rhizomes. The most widely studied species
      was Salvia miltiorrhiza Bunge, and the compound most frequently used as a
      pharmacokinetic marker was berberine. CONCLUSION: Most studies were performed
      using the Sprague Dawley rat model, and the preparations were mainly administered
      orally in a single dose. Quantification of plasma concentrations of
      pharmacokinetic markers was performed mainly by liquid-liquid extraction,
      followed by high performance liquid chromatography coupled to mass spectrometry
      detector. In conclusion, in recent years there has been an increasing interest
      among researchers worldwide in the study of pharmacokinetics of bioactive
      compounds in botanical drugs and plant extracts, especially those from the
      Traditional Chinese Medicine.

PMID- 28494733
TI  - Phage-Mediated Gene Therapy.
AB  - BACKGROUND: Bacteriophages (bacterial viruses) have long been under investigation
      as vectors for gene therapy. Similar to other viral vectors, the phage coat
      proteins have evolved over millions of years to protect the viral genome from
      degradation post injection, offering protection for the valuable therapeutic
      sequence. MATERIALS AND METHODS: However, what sets phage apart from other viral
      gene delivery vectors is their safety for human use and the relative ease by
      which foreign molecules can be expressed on the phage outer surface, enabling
      highly targeted gene delivery. The latter property also makes phage a popular
      choice for gene therapy target discovery through directed evolution. Although
      promising, phage-mediated gene therapy faces several outstanding challenges, the
      most notable being lower gene delivery efficiency compared to animal viruses,
      vector stability, and nondesirable immune stimulation. RESULT: This review
      presents a critical review of promises and challenges of employing phage as gene
      delivery vehicles as well as an introduction to the concept of phage-based
      microbiome therapy as the new frontier and perhaps the most promising application
      of phage-based gene therapy.

PMID- 28494734
TI  - Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug
      Delivery.
AB  - There is a growing interest in transdermal delivery systems because of their
      noninvasive, targeted, and on-demand delivery of gene and drugs. However,
      efficient penetration of therapeutic compounds into the skin is still challenging
      largely due to the impermeability of the outermost layer of the skin, known as
      stratum corneum. Recently, there have been major research activities to enhance
      the skin penetration depth of pharmacological agents. This article reviews recent
      advances in the development of various strategies for skin penetration
      enhancement. We show that approaches such as ultrasound waves, laser, and
      microneedle patches have successfully been employed to physically disrupt the
      stratum corneum structure for enhanced transdermal delivery. Rather than physical
      approaches, several non-physical route have also been utilized for efficient
      transdermal delivery across the skin barrier. Finally, we discuss some clinical
      applications of transdermal delivery systems for gene and drug delivery. This
      paper shows that transdermal delivery devices can potentially function for
      diverse healthcare and medical applications while further investigations are
      still necessary for more efficient skin penetration of gene and drugs.

PMID- 28494735
TI  - Perspectives of Gene Therapies in Autosomal Dominant Polycystic Kidney Disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common inherited kidney disease in the clinic. The predominant clinical
      manifestation is bilateral and progressive cysts formation in the kidneys,
      impairs normal renal parenchyma, and ultimately leads to endstage renal disease
      (ESRD). ADPKD is a heterogenic disease which is resulted from the mutations of
      PKD1 or PKD2 genes which encode polycystin-1 (PC1) and -2 (PC2), thereby multiple
      cell signaling pathways are involved. METHOD: Although causative genes and
      aberrant signaling pathways have been investigated for decades, lack of effective
      and less side-effect treatment for the disease still perplex vast clinicians.
      Therefore, development of new therapeutic approaches for ADPKD is currently very
      much desired. CONCLUSION: This review will center on pathogenesis of ADPKD, and
      thereafter gene transfer will be discussed as potential treatment for the
      disease. New therapeutic interventions will bring further hope to improve
      prognosis of this incurable disease.

PMID- 28494736
TI  - Smart Micro/Nano-robotic Systems for Gene Delivery.
AB  - BACKGROUND: Small scale robotics have attracted growing attention for the
      prospect of targeting and accessing cell-sized sites, necessary for high
      precision biomedical applications and drug/gene delivery. The loss of controlled
      gene therapy, inducing systemic side effects and reduced therapeutic efficiency,
      can be settled utilizing these intelligent carriers. METHODS: Newly proposed
      solutions for the main challenges of control, power supplying, gene release and
      final carrier extraction/degradation have shifted these smart miniature robots to
      the point of being employed for practical applications of transferring
      oligonucleotides (pDNA, siRNA, mRNA, etc.) in near future. CONCLUSION: In this
      paper, different scenarios and their endeavors to address the vital working
      demands and steps, in particular, carrier attachment and release, cell
      internalization, manipulation concerns as well as actuation systems are
      discussed.This review highlights some promising experimental results showing
      controlled gene release of robotic systems in comparison with current non
      specific gene delivery methods.

PMID- 28494737
TI  - Lipid Nanoparticles as Potential Gene Therapeutic Delivery Systems for Oral
      Administration.
AB  - BACKGROUND: Gene therapy has experimented an increasing attention in the last
      decades, due to its enormous potential applications in the medical field. It can
      be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides)
      to treat or prevent a disease state, generally a geneticbased one. APPLICATION:
      Other applications, like treating viral, bacterial or parasite infections or
      development of vaccines are gaining also interest. Efficient gene therapy is
      mainly dependent on the ability of the highly labile genetic material to reach
      the therapeutic target. For this purpose, different delivery systems have been
      designed and extensively investigated. Nanoparticles offer a broad range of
      possibilities in design, being prepared using biocompatible and biodegradable
      excipients, being therefore generally considered as safe. CONCLUSION: Oral
      delivery of the genetic material is also a great challenge, due to the complexity
      of this specific biological barrier. Special attention to all the intrinsic
      hazards for gene delivery due to the barrier must be taken into account during
      the particle design process. Particle design will also allow targeting to
      specific sites of the gastrointestinal tract. Solid lipid nanoparticles have been
      extensively studied in the oral drug delivery field, and also in gene delivery
      through other administration routes, but still not explored in oral gene
      delivery. In this manuscript, design considerations and particle-cell interaction
      mechanisms will be extensively reviewed, focusing on the oral route to encourage
      the scientific community to explore these valuable carriers for oral gene
      delivery.

PMID- 28494738
TI  - Smart and Controllable rAAV Gene Delivery Carriers in Progenitor Cells for Human
      Musculoskeletal Regenerative Medicine with a Focus on the Articular Cartilage.
AB  - Cell therapy using mesenchymal stem cells (MSCs) is a powerful tool for the
      treatment of various diseases and injuries. Still, important limitations
      including the large amounts of cells required for application in vivo and the age
      related decline in lifespan, proliferation, and potency may hinder the use of
      MSCs in patients. In this regard, gene therapy may offer strong approaches to
      optimize the use of MSCs for regenerative medicine. Diverse nonviral and viral
      gene vehicles have been manipulated to genetically modify MSCs, among which the
      highly effective and relatively safe recombinant adeno-associated viral (rAAV)
      vectors that emerged as the preferred gene delivery system to treat human
      disorders. Yet, clinical adaptation of such gene vehicles may be limited by
      several hurdles, including the possibility of dissemination to nontarget sites
      and the presence of immune and toxic responses in the host organism that may
      impair their therapeutic actions. The use of smart biomaterials acting as
      interfaces to enhance the temporal and spatial presentation of therapeutic agents
      in the target place and/or acting as scaffolding for MSC growth is an innovative,
      valuable approach to overcome these shortcomings that else restrain the efficacy
      of such potent cell populations. Here, we provide an overview on the most recent
      tissue engineering approaches based on the use of biomaterials acting as vehicles
      for rAAV vectors to target MSCs directly in the recipient (in vivo strategy) or
      as supportive matrices for rAAV-modified MSCs for indirect cell reimplantation
      (ex vivo strategy) as means to activate the reparative processes in tissues of
      the musculoskeletal system.

PMID- 28494739
TI  - Gene Delivery Particle Engineering Strategies for Shape-dependent Targeting of
      Cells and Tissues.
AB  - BACKGROUND: Successful gene delivery requires overcoming both systemic and
      intracellular obstacles before the nucleic acid cargo can successfully reach its
      tissue and subcellular target location. Materials & Methods: Non-viral mechanisms
      to enable targeting while avoiding off-target delivery have arisen via
      biological, chemical, and physical engineering strategies. DISCUSSION: Herein we
      will discuss the physical parameters in particle design that promote tissue- and
      cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such
      as circulation, tissue localization, and clearance, as well as cell-scale
      obstacles, such as cellular uptake and nucleic acid packaging. CONCLUSION: In
      particular, we will focus on engineering particle shape and size in order to
      enhance delivery and promote precise targeting. We will also address methods to
      program or change particle shape in situ using environmentally triggered cues.

PMID- 28494740
TI  - Nucleic Acids-based Nanotherapeutics Crossing the Blood Brain Barrier.
AB  - The restless endeavors revealing the molecular pathways underlying many
      neurodegenerative diseases and brain tumors have paved the way for the
      introduction of the selective exogenous gene-based therapeutics. The implicated
      active biomolecules encompass mainly negatively-charged nucleic acids ranging
      from DNA, mRNA, non-coding RNAs (small-interfering RNA, siRNA, and microRNA,
      miRNA), to antisense oligonucleotides. They selectively interfere with the genes
      translational and/or transcriptional processes. Although many reviews previously
      addressed brain targeting, a thorough correlation between the molecular
      properties of these biomacromolecules, the nature of blood brain barrier (BBB) in
      the accompanying pathological condition, the intracellular targets, as well as
      the design of the delivery system which will transport the bioactive cargo to the
      target cells attempting efficient delivery to the active sites in the brain will
      be appraised. In this review, we will further discuss the tremendous advances in
      non-viral gene delivery nanosystems currently investigated (starting from self
      assembled nanoplexes using cationic polymers or lipids and going through
      liposomes, aptamers, polymersomes, exosomes, dendrimers and nanoparticles).
      Unlike previous reviews on this topic, functionalization strategies of the
      nanocarriers promoting either surface receptor binding or intracellular targeting
      of the cranial cells will be highlighted, with special emphasis on tailoring
      smart nanomedicines according to the CNS disease condition. In addition, newly
      developed evaluation approaches, cell culture models studying BBB permeability
      and manipulation of the barrier function of the brain via focused ultrasound will
      be addressed.

PMID- 28494741
TI  - Delivering siRNA with Dendrimers: In Vivo Applications.
AB  - Over the last decades, gene therapy has emerged as a pioneering therapeutic
      approach to treat or prevent several diseases. Among the explored strategies, the
      short-term silencing of protein coding genes mediated by siRNAs has a good
      therapeutic potential in a clinical setting. However, the widespread use of siRNA
      will require the development of clinically suitable, safe and effective vehicles
      with the ability to complex and deliver siRNA into target cells with minimal
      toxicity. Lately, dendrimers have gained considerable attention as non-viral
      vectors in nucleic acid delivery due to their unique structural characteristics
      (globular, well defined and highly branched structure, multivalency, low
      polydispersity and tunable nanosize), along with their relevant capacity to
      complex and protect nucleic acids in compact nanostructures, which can be
      functionalized with targeting moieties in order to get cell specificity. Here, we
      present an overview of the state-of-the-art of the most significant and recent
      advances on the use of dendrimers as siRNA delivery vectors, with particular
      focus on the in vivo applications. We will cover the use of different dendrimers,
      distinct administration routes, toxicity issues, as well as the target tissue or
      disease, highlighting the potential of dendrimers as nanocarriers for therapeutic
      and biomedical applications.

PMID- 28494742
TI  - Potential Gene Therapy Towards Treating Neurodegenerative Disea ses Employing
      Polymeric Nanosystems.
AB  - BACKGROUND: Recent integrated approaches involving nanotechnology and gene
      therapy have accelerated development of efficient drug delivery to the central
      nervous system (CNS). Neurodegenerative disorders are closely associated with
      genetic inheritance and mutation. MATERIALS: Nanotechnology has allowed effective
      engineering of various such polymeric structures. Moreover, availability of a
      wide array of polymeric materials has enabled fabrication of biocompatible and
      biodegradable delivery vehicles. Our manuscript focuses on the ideal features and
      properties of polymeric nanoparticles that have enabled successful gene therapy
      for neurodegenerative disorders, as well as the challenges that are posing
      difficulties in their practical application. We have highlighted these aspects
      through examples of polymeric nanoparticles that have exhibited therapeutic
      promise in the treatment of neurological disorders and mutations. METHODS:
      Complete cure of these diseases is a challenging task and gene therapy appears as
      a realistic approach for their treatment. Gene therapy allows effective
      replacement or suppression of faulty genes, thereby increasing chances for neuron
      survival and repair. However, successful delivery of naked genetic material to
      CNS faces severe obstacles due to possible degradation and restricted
      transportation of these biological entities across the blood brain barrier (BBB).
      Structurally, the BBB is composed of several tight junctions, making the membrane
      highly selective towards the entry of molecules. CONCLUSION: In order to target
      BBB for treating neurodegenerative diseases, it is essential to develop a tailor
      made system that may not only cross this barrier, but also effectively modulate
      the expression of disease-causing genes. Stabilization of therapeutic genes and
      their effective, targeted delivery may be possible using polymeric nanoparticles
      as carriers.

PMID- 28494743
TI  - Osteonecrosis of the Jaw and Angiogenesis inhibitors: A Revival of a Rare but
      Serous Side Effect.
AB  - Osteonecrosis of the jaw (ONJ) is a rare treatment related side effect that was
      firstly described in 2002 through a case report in metastatic bone cancer patient
      treated with bisphosphonates (BPs) therapy. ONJ is defined as an eight weeks or
      longer clinical finding of exposed bone in the oral cavity without response to
      appropriate therapy. The diagnosis is mainly clinical but often requires a
      radiological confirmation with an orthopantomography. So it must be made by a
      dental specialist with sufficient experience on ONJ and requires a detailed
      anamnestic exploration of comorbidities and treatments history. In particular,
      ONJ affects a wide number of oncologic patients treated with BPs for bone
      metastatic cancers and, more recently, with anti-angiogenic drugs. The aim of
      this this paper is to describe diagnosis and classification of this rare but
      serious side effect and its pathophysiology. In particular, we provide a detailed
      description of clinical evidences upon the relationship between anti-angiogenic
      drugs and ONJ. Considering the evolving of cancer epidemiology with a greater
      number of cancer surviving patients, this side effect always deserves more
      attention. We conclude that ONJ must be always carefully investigated and
      prevented with a multidisciplinary approach involving oncologist, radiation
      oncologist and skilled dental practitioner when a cancer patient must begin a BP
      or an antiangiogenic treatment.

PMID- 28494744
TI  - Targeting Nrf2 in Protection Against Renal Disease.
AB  - BACKGROUND: Renal disease is a serious health problem, with increasing incidence
      and prevalence. Oxidative stress and inflammation play a key role in the
      pathogenesis and progression of renal disease. Therefore, therapeutic approaches
      to decrease oxidative stress should be of interest. OBJECTIVE: This review aims
      to provide a comprehensive and updated overview of the protective mechanisms
      mediated by Nrf2 (nuclear factor erythroid 2-related factor 2), a description of
      novel compounds that target Nrf2, its effectiveness to prevent renal disease and
      the on-going clinical trials for this pathological condition. METHODS: We
      undertook a structured search of bibliographic databases for peer-reviewed
      research in literature about Nrf2 activators and renal disease. RESULTS: The
      transcription factor Nrf2 is an emerging regulator of cellular resistance to
      oxidants and inflammation. Nrf2 controls the basal and induced expression of a
      couple of cytoprotective and antiinflammatory genes that regulate the
      physiological and pathophysiological outcomes of oxidant exposure. We have
      analyzed numerous findings showing that Nrf2 induction protects against oxidative
      stress and modulates inflammation in acute kidney injury and chronic kidney
      disease progression. However, few clinical trials have been performed in humans.
      Recent studies suggested that renoprotective effects of Nrf2 activation are
      observed at low doses, whereas harmful effects appear at higher concentrations.
      CONCLUSION: The findings of this review confirm that novel studies are necessary
      to address whether Nrf2-targeting may be a safe therapeutic approach to decrease
      renal disease progression in humans.

PMID- 28494745
TI  - Global View on Rare Diseases: A Mini Review.
AB  - BACKGROUND: Rare diseases are often serious, life-threatening and debilitating
      group of disorders. Nowadays, there are approximately 8,000 rare diseases and it
      is estimated that 350 million people are affected by these conditions worldwide.
      Unfortunately, rare diseases are quite complex and chronic, only a small number
      of these diseases can be relevantly diagnosed and treated, and lifelong treatment
      is often required. OBJECTIVE: The purpose of this mini review is to explore the
      issue of rare diseases, describe their classification, discuss the current
      treatment and management and set future research in this field. METHODS: The
      methods applied in this review include literature review of the world's
      acknowledged databases such as PubMed, Springer and Web of Science, especially in
      the period of 2000 to 2015. Furthermore, a method of comparison and evaluation of
      the findings from the relevant sources is used. RESULTS: The findings confirm
      that rare diseases are still quite difficult to diagnose due to their
      comorbidities. Once they are diagnosed, they demand costly and long-term
      treatment, which raises concerns of national governments. CONCLUSION: Therefore
      more research should be done in the space of rare diseases in order to broaden
      knowledge about them, their diagnosis and treatment, which will then lead to
      better training of medical staff, and ultimately will benefit the patients.

PMID- 28494746
TI  - Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.
AB  - BACKGROUND: Fungi are a well-known and valuable source of compounds of
      therapeutic relevance, in particular of novel anticancer compounds. Although
      seldom obtainable through isolation from the natural source, the total organic
      synthesis still remains one of the most efficient alternatives to resupply them.
      Furthermore, natural product total synthesis is a valuable tool not only for
      discovery of new complex biologically active compounds but also for the
      development of innovative methodologies in enantioselective organic synthesis.
      METHODS: We undertook an in-depth literature searching by using chemical
      bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive
      insight into the wide research field. The literature has been then screened,
      refining the obtained results by subject terms focused on both biological
      activity and innovative synthetic procedures. RESULTS: The literature on fungal
      metabolites has been recently reviewed and these publications have been used as a
      base from which we consider the synthetic feasibility of the most promising
      compounds, in terms of anticancer properties and drug development. In this paper,
      compounds are classified according to their chemical structure. CONCLUSION: This
      review summarizes the anticancer potential of fungal metabolites, highlighting
      the role of total synthesis outlining the feasibility of innovative synthetic
      procedures that facilitate the development of fungal metabolites into drugs that
      may become a real future perspective. To our knowledge, this review is the first
      effort to deal with the total synthesis of these active fungi metabolites and
      demonstrates that total chemical synthesis is a fruitful means of yielding fungal
      derivatives as aided by recent technological and innovative advancements.

PMID- 28494747
TI  - New Diagnostic and Therapeutic Aspects of Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of
      its silent nature, the disease is often only diagnosed once it has reached an
      advanced, frequently inoperable stage. To date, we have no biomarkers that
      facilitate earlier diagnosis, leaving sufficient time for curative therapy that
      effectively lowers the very high mortality rate of this cancer entity. Because of
      this, the life expectancy of patients with PDAC is low (i.e. <= 6% five-year
      survival rates). New data, including particular genetic signatures and features
      of the stromal architecture of PDAC tumors, may better explain their
      aggressiveness, their relatively long-lasting painless expansion, and why
      chemotherapy so frequently fails. The typical tumor-induced stromal desmoplasia
      is characterized by cancer-associated fibroblasts (CAFs), decreased immune
      surveillance, cancer-associated neural remodeling, and a very low vascular
      density. This stromal microenvironment generates hypoxia, nutrient deficiency,
      immune suppression, and chemoresistance. The combination of factors results in a
      vicious disease that begins with the long-lasting, asymptomatic development of a
      large tumor mass, followed by a delayed diagnosis with a high percentage of
      inoperable states, exhibiting a poor response to all conservative therapeutic
      options, including radiation, and which ends with metastasis resulting in a rapid
      fatal outcome. OBJECTIVE: In this article, we review coherences on genetic,
      cellular, immunological, Nano medical and stromal characteristics of PDAC tissue,
      and discuss metabolic abnormalities associated with and/or preceding the tumor
      progression rate. CONCLUSION: A more comprehensive understanding of the
      underlying mechanisms can improve the diagnostic and therapeutic management of
      patients suffering from this devastating type of cancer.

PMID- 28494748
TI  - The novelty of bupropion as a dopaminergic antidepressant for the treatment of
      adult attention deficit hyperactive disorder.
AB  - Attention deficit hyperactive disorder (ADHD), a hyperactivity disorder that is
      prevalent among children may continue as an adulthood attention deficit. To date,
      treating an individual with an adult ADHD may be an arduous task as it involved
      numerous challenges, such as a need for high index of suspicion to diagnose this
      medical condition. Many psychiatric disorders masquerade as ADHD and delayed the
      necessary assessment and proper treatment for the debilitating medical condition.
      Adult ADHD would also be misdiagnosed (or under diagnosed) due to the facts that
      this medical condition is being masked by his or her high level of
      intellectuality achievement. As the ADHD in adult persisted, it may end-up with
      impairment in the personal-social-occupational function, in which the management
      became a great challenge. The treatment of ADHD can be optimized by using various
      drugs targets agents like a norepinephrine-dopamine reuptake inhibitor (NDRI),
      with or without psycho stimulants like methylphenidate, which was marketed as
      ritalin. Bupropion, a NDRI has a novel effect on ADHD as the molecule exerts its
      effects by modulating the reward-pleasure mesolimbic dopaminergic system, and at
      the same time regulating the elevating mood dimension of the noradrenergic
      neurotransmission. The role of bupropion in the neural and psychopharmacological
      perspective treatment of ADHD was deliberated. This review highlights the novelty
      effects of bupropion in treating ADHD, together with the help of other successful
      bio-psycho-social measures, which may offer a great assistance to the
      psychiatrists in treating their patients to the level best.

PMID- 28494749
TI  - Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How
      They All Come Together?
AB  - In the past decade, many studies have highlighted the role of metabotropic
      glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related
      biological effects such as alcohol consumption, alcohol-seeking and relapse-like
      behaviors. Taken together, these findings suggest that pharmacological agents
      acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are
      present abundantly in brain regions known to be involved in emotion regulation,
      motivation and drug administration. On a cellular level, they are primarily
      located at the postsynaptic part of the neuron where the receptor is functionally
      linked to various downstream proteins that are involved in cell signaling and
      gene transcription that mediate the alcohol-induced neuroplasticity. As well, the
      discovery of a functional link between mGlu5 and a specific isozyme, Protein
      Kinase C epsilon (PKCepsilon) in mediating the attenuating effects of selective
      negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine
      (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked
      interesting speculations. In this article, we shall review the following: the
      effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of
      mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being
      studied both at pre-clinical and clinical stages; and the mechanisms underlying
      the pharmacological effects of these drugs.

PMID- 28494750
TI  - Direct and indirect risk associated with the use of dietary supplements among
      persons with dementia in a Norwegian memory clinic.
AB  - BACKGROUND: The use of dietary supplements (DS) is common among persons with
      dementia. Direct risks associated with DS use include adverse events and DS-drug
      interactions. A direct risk is a risk caused by the treatment itself. Indirect
      risks are related to the treatment setting, such as the conditions of use, and
      not to the treatment itself. Because dementia symptoms may reduce a person's
      ability to cope with the administration of DS, the use of DS may pose a threat to
      safety as an indirect risk. The aim of this study was to describe the extent of
      DS use among persons with dementia in ambulatory care and to identify some
      relevant direct and indirect risks related to DS use. METHODS: We conducted a
      survey among 151 persons with dementia attending an outpatient memory clinic in
      Northern Norway. Study measurements included: the participants' characteristics,
      cognitive functioning, functioning in the activities of daily living (ADL), and
      the use of DS and prescription drugs (PD). We assessed direct risks by evaluating
      potential DS-drug interactions and indirect risks by evaluating the conditions
      under which it was used. RESULTS: Forty-six percent (n = 70) of the persons with
      dementia used DS. Ninety-seven percent (n = 147) used PD. We found potentially
      clinically relevant DS-drug interactions representing a direct risk in eight
      persons with dementia (11% of users). While only 36% (n = 26) of the participants
      received assistance with the administration of DS, 73% (n = 106) received
      assistance with the administration of PD. Persons with dementia living alone were
      at risk of not receiving assistance, as home care service seldom was involved in
      DS administration. Data indicated that assistance with DS administration was not
      provided for all persons with dementia in need, representing an indirect risk to
      these persons. Only one-third of the persons with dementia and half of the
      caregivers were aware of the general risks of adverse events and interactions
      associated with the use of DS. CONCLUSIONS: Persons with dementia use DS
      frequently, yet DS use may be associated with direct and indirect risks to
      patient safety as potentially clinically relevant interactions were discovered
      and DS intake often was unsupervised.

PMID- 28494751
TI  - Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension.
AB  - BACKGROUND: Droxidopa, a prodrug of norepinephrine, was approved for treatment of
      neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based
      on 3 randomized double-blind studies. We performed safety and efficacy analyses
      of this pooled dataset (n = 460). METHODS: Efficacy was assessed using
      Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual
      items). Safety and tolerability were also examined. RESULTS: Droxidopa improved
      virtually all nOH symptom scores compared with placebo, significantly reducing
      OHQ composite score (-2.68 +/- 2.20 vs -1.82 +/- 2.34 units; P < 0.001),
      dizziness/lightheadedness score (-3.0 +/- 2.9 vs -1.8 +/- 3.1 units; P < 0.001),
      and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue
      [P <= 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of
      daily living (standing a long time, walking a short time, and walking a long time
      [P <= 0.003]) and significantly increased upright systolic blood pressure (11.5
      +/- 20.5 vs 4.8 +/- 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in
      patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts
      droxidopa to norepinephrine), but its efficacy was numerically greater in non
      DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were
      similar between groups. Supine hypertension rates were low, but slightly higher
      in patients receiving droxidopa (<=7.9% vs <=4.6% for placebo); patients with
      severe hypertension at screening were excluded from these studies. CONCLUSIONS:
      Droxidopa is effective for the treatment of nOH in patients with primary
      autonomic disorders and is generally well-tolerated. A longer trial is underway
      to confirm efficacy beyond the <=2 to 10 - week period assessed in the current
      trials. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00782340 , first
      received October 29, 2008; NCT00633880 , first received March 5, 2008; and
      NCT01176240 , first received July 30, 2010.

PMID- 28494752
TI  - MDA-MET-conditioned-medium augments the chemoattractant-dependent migration of
      MDA-MET cells towards hFOB-conditioned medium and increases collagenase activity.
AB  - BACKGROUND: Metastasis of breast cancer displays site-specificity towards bone.
      Recently, studies have emerged indicating that primary tumors may remotely
      influence creation of a pre-metastatic niche. In this study, we used human fetal
      osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing
      derivative of the breast cancer cell line MDA-MB-231. We examined 1) whether
      secreted factors from MDA-MET cells increase generation of chemoattractants by
      human foetal osteoblastic cells 2) whether MDA-MET cells were responsive to these
      chemoattractants and 3) the identity of these chemoattractants. METHODS: Human
      foetal osteoblastic cells were treated with conditioned medium of MDA-MET cells
      for 24 hours and then washed with phosphate-buffered saline. Serum-free
      replacement medium was conditioned by treated hFOB cells for 18 hours, before its
      use in in vitro quantification of MDA-MET migration. We also quantified collagen
      levels and collagenase activity in conditioned medium from human foetal
      osteoblastic cells. RESULTS: Conditioned medium from human foetal osteoblastic
      cells that had been treated with MDA-MET-conditioned medium attracted more MDA
      MET cells than hFOB cells pre-exposed to their own medium. This conditioned
      medium had increased collagenase activity. The addition of bacterial collagenase
      removed the ability of conditioned medium from human foetal osteoblastic cells to
      attract MDA-MET cells. CONCLUSIONS: Our data suggest that an increase in
      collagenase activity in osteoblastic cells induced by their exposure to breast
      cancer cell-secreted factors may increase their ability to attract breast cancer
      cells.

PMID- 28494753
TI  - Preventing sickness absenteeism among employees with common mental disorders or
      stress-related symptoms at work: Design of a cluster randomized controlled trial
      of a problem-solving based intervention versus care-as-usual conducted at the
      Occupational Health Services.
AB  - BACKGROUND: Common mental disorders (CMDs) are among the leading causes of sick
      leave in Sweden and other OECD countries. They result in suffering for the
      individual and considerable financial costs for the employer and for society at
      large. The occupational health service (OHS) can offer interventions in which
      both the individual and the work situation are taken into account. The aim of
      this paper is to describe the design of a study evaluating the effectiveness of
      an intervention given at the OHS to employees with CMDs or stress-related
      symptoms at work. In addition, intervention fidelity and its relation to the
      outcome will be assessed in a process analysis. METHODS: The study is designed as
      a cluster randomized trial in which the participating OHS consultants are
      randomized into either delivering the intervention or performing care as usual.
      Employees with CMDs or stress-related symptoms at work are recruited
      consecutively by the OHS consultants. The intervention aims to improve the match
      between the employee and the job situation. Interviews are held individually with
      the employee and the nearest supervisor, after which a joint meeting with both
      the employee and the supervisor takes place. A participatory approach is applied
      by which the supervisor and the employee are guided by the OHS consultant and
      encouraged to actively take part in problem solving concerning the work
      situation. Outcomes will be assessed at baseline and at six and 12 months. A long
      term follow-up at 3 years will also be performed. The primary outcome is
      registered sickness absence during a 1-year period after study inclusion.
      Secondary outcomes are mental health and work ability. The intervention's cost
      effectiveness, compared to treatment as usual, both for society and for the
      employer will be evaluated. A process evaluation by both the OHS consultants and
      the employee will be carried out. DISCUSSION: The study includes analyses of the
      effectiveness of the intervention (clinical and economic) as well as an analysis
      of its implementation at the participating OHSs. Possible methodological
      challenges such as selection bias and risk of contamination between OHS
      consultants delivering the experimental condition and consultants giving usual
      care are discussed. TRIAL REGISTRATION: ClinicalTrials NCT02563743 Sep 28 2015.

PMID- 28494754
TI  - Circulating cathelicidin levels correlate with mucosal disease activity in
      ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical
      prognosis in inflammatory bowel disease.
AB  - BACKGROUND: Cathelicidin (LL-37) is an antimicrobial peptide known to be
      associated with various autoimmune diseases. We attempt to determine if
      cathelicidin can accurately reflect IBD disease activity. We hypothesize that
      serum cathelicidin correlates with mucosal disease activity, stricture, and
      clinical prognosis of IBD patients. METHODS: Serum samples were collected from
      two separate cohorts of patients at the University of California, Los Angeles.
      Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted
      of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA.
      Data from both cohorts were combined for calculation of accuracies in indicating
      mucosal disease activity, relative risks of stricture, and odds ratios of
      predicting disease development. RESULTS: Serum cathelicidin levels were inversely
      correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of
      CD patients. Among IBD patients with moderate or severe initial disease activity,
      the patients with high initial LL-37 levels had significantly better recovery
      than the patients with low initial LL-37 levels after 6-18 months, suggesting
      that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and
      CRP levels was more accurate than CRP alone or LL-37 alone in the correlation
      with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a
      significantly elevated risk of intestinal stricture in CD patients. CONCLUSION:
      Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC
      patients. LL-37 can predict future clinical activity in IBD patients and indicate
      risk of intestinal stricture in CD patients.

PMID- 28494755
TI  - Transcriptome analysis of the whitefly, Bemisia tabaci MEAM1 during feeding on
      tomato infected with the crinivirus, Tomato chlorosis virus, identifies a
      temporal shift in gene expression and differential regulation of novel orphan
      genes.
AB  - BACKGROUND: Whiteflies threaten agricultural crop production worldwide, are
      polyphagous in nature, and transmit hundreds of plant viruses. Little is known
      how whitefly gene expression is altered due to feeding on plants infected with a
      semipersistently transmitted virus. Tomato chlorosis virus (ToCV; genus
      Crinivirus, family Closteroviridae) is transmitted by the whitefly (Bemisia
      tabaci) in a semipersistent manner and infects several globally important
      agricultural and ornamental crops, including tomato. RESULTS: To determine
      changes in global gene regulation in whiteflies after feeding on tomato plants
      infected with a crinivirus (ToCV), comparative transcriptomic analysis was
      performed using RNA-Seq on whitefly (Bemisia tabaci MEAM1) populations after 24,
      48, and 72 h acquisition access periods on either ToCV-infected or uninfected
      tomatoes. Significant differences in gene expression were detected between
      whiteflies fed on ToCV-infected tomato and those fed on uninfected tomato among
      the three feeding time periods: 447 up-regulated and 542 down-regulated at 24 h,
      4 up-regulated and 7 down-regulated at 48 h, and 50 up-regulated and 160 down
      regulated at 72 h. Analysis revealed differential regulation of genes associated
      with metabolic pathways, signal transduction, transport and catabolism,
      receptors, glucose transporters, alpha-glucosidases, and the uric acid pathway in
      whiteflies fed on ToCV-infected tomatoes, as well as an abundance of
      differentially regulated novel orphan genes. Results demonstrate for the first
      time, a specific and temporally regulated response by the whitefly to feeding on
      a host plant infected with a semipersistently transmitted virus, and advance the
      understanding of the whitefly vector-virus interactions that facilitate virus
      transmission. CONCLUSION: Whitefly transmission of semipersistent viruses is
      believed to require specific interactions between the virus and its vector that
      allow binding of virus particles to factors within whitefly mouthparts. Results
      provide a broader understanding of the potential mechanism of crinivirus
      transmission by whitefly, aid in discerning genes or loci in whitefly that
      influence virus interactions or transmission, and subsequently facilitate
      development of novel, genetics-based control methods against whitefly and
      whitefly-transmitted viruses.

PMID- 28494756
TI  - Solving the master equation for Indels.
AB  - BACKGROUND: Despite the long-anticipated possibility of putting sequence
      alignment on the same footing as statistical phylogenetics, theorists have
      struggled to develop time-dependent evolutionary models for indels that are as
      tractable as the analogous models for substitution events. MAIN TEXT: This paper
      discusses progress in the area of insertion-deletion models, in view of recent
      work by Ezawa (BMC Bioinformatics 17:304, 2016); (BMC Bioinformatics 17:397,
      2016); (BMC Bioinformatics 17:457, 2016) on the calculation of time-dependent gap
      length distributions in pairwise alignments, and current approaches for extending
      these approaches from ancestor-descendant pairs to phylogenetic trees.
      CONCLUSIONS: While approximations that use finite-state machines (Pair HMMs and
      transducers) currently represent the most practical approach to problems such as
      sequence alignment and phylogeny, more rigorous approaches that work directly
      with the matrix exponential of the underlying continuous-time Markov chain also
      show promise, especially in view of recent advances.

PMID- 28494757
TI  - COPD monocytes demonstrate impaired migratory ability.
AB  - BACKGROUND: Increased lung macrophage numbers in COPD may arise from upregulation
      of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine
      receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are
      known to be elevated in COPD lungs. The objective of this study was to
      investigate mechanisms of monocyte recruitment to the lung in COPD, including the
      role of CCR5 signalling. METHODS: Ninety one COPD patients, 29 smokers (S) and 37
      non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and
      soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by
      flow cytometry) and monocyte isolation for cell migration and quantitative
      polymerase chain reaction studies. Lung tissue was used for immunohistochemistry.
      RESULTS: Plasma IL-6 and sIL-6R levels were increased in COPD. Greater
      proportions of COPD CD14++CD16+ monocytes expressed CCR5 compared to controls.
      Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression. COPD
      monocytes demonstrated impaired migration towards sputum supernatant compared to
      NS (% migration, 4.4 vs 11.5, respectively; p < 0.05). Pulmonary microvessels
      showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS,
      (9.3% vs 83.1%, respectively). The proportion of replicating Ki67+ alveolar
      macrophages was reduced in COPD compared to NS. All alveolar macrophages from
      COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present
      in non-smokers or COPD ex-smokers. CONCLUSION: COPD monocytes show decreased
      migratory ability despite increased CCR5 expression. Increased COPD lung
      macrophage numbers may be due to delayed apoptosis.

PMID- 28494758
TI  - Physician job satisfaction related to actual and preferred job size.
AB  - BACKGROUND: Job satisfaction is essential for physicians' well-being and patient
      care. The work ethic of long days and hard work that has been advocated for
      decades is acknowledged as a threat for physicians' job satisfaction, well-being,
      and patient safety. Our aim was to determine the actual and preferred job size of
      physicians and to investigate how these and the differences between them
      influence physicians' job satisfaction. METHOD: Data were retrieved from a
      larger, longitudinal study among physicians starting medical training at
      Groningen University in 1982/83/92/93 (N = 597). Data from 506 participants (85%)
      were available for this study. We used regression analysis to investigate the
      influence of job size on physicians' job satisfaction (13 aspects) and ANOVA to
      examine differences in job satisfaction between physicians wishing to retain,
      reduce or increase job size. RESULTS: The majority of the respondents (57%) had
      an actual job size less than 1.0 FTE. More than 80% of all respondents preferred
      not to work full-time in the future. Respondents' average actual and preferred
      job sizes were .85 FTE and .81 FTE, respectively. On average, respondents who
      wished to work less (35% of respondents) preferred a job size reduction of 0.18
      FTE and those who wished to work more (12%) preferred an increase in job size of
      0.16 FTE. Job size influenced satisfaction with balance work-private hours most
      (beta = -.351). Physicians who preferred larger job sizes were - compared to the
      other groups of physicians - least satisfied with professional accomplishments.
      CONCLUSIONS: A considerable group of physicians reported a gap between actual and
      preferred job size. Realizing physicians' preferences as to job size will hardly
      affect total workforce, but may greatly benefit individual physicians as well as
      their patients and society. Therefore, it seems time for a shift in work ethic.

PMID- 28494760
TI  - The Picture Talk Project: Starting a Conversation with Community Leaders on
      Research with Remote Aboriginal Communities of Australia.
AB  - BACKGROUND: Researchers are required to seek consent from Indigenous communities
      prior to conducting research but there is inadequate information about how
      Indigenous people understand and become fully engaged with this consent process.
      Few studies evaluate the preference or understanding of the consent process for
      research with Indigenous populations. Lack of informed consent can impact on
      research findings. METHODS: The Picture Talk Project was initiated with senior
      Aboriginal leaders of the Fitzroy Valley community situated in the far north of
      Western Australia. Aboriginal people were interviewed about their understanding
      and experiences of research and consent processes. Transcripts were analysed
      using NVivo10 software with an integrated method of inductive and deductive
      coding and based in grounded theory. Local Aboriginal interpreters validated
      coding. Major themes were defined and supporting quotes sourced. RESULTS:
      Interviews with Aboriginal leaders (n = 20) were facilitated by a local
      Aboriginal Community Navigator who could interpret if necessary and provide
      cultural guidance. Participants were from all four major local language groups of
      the Fitzroy Valley; aged 31 years and above; and half were male. Themes emerging
      from these discussions included Research-finding knowledge; Being respectful of
      Aboriginal people, Working on country, and Being flexible with time; Working
      together with good communication; Reciprocity-two-way learning; and Reaching
      consent. CONCLUSION: The project revealed how much more there is to be learned
      about how research with remote Aboriginal communities should be conducted such
      that it is both culturally respectful and, importantly, meaningful for
      participants. We identify important elements in community consultation about
      research and seeking consent.

PMID- 28494759
TI  - Time-resolved dual transcriptomics reveal early induced Nicotiana benthamiana
      root genes and conserved infection-promoting Phytophthora palmivora effectors.
AB  - BACKGROUND: Plant-pathogenic oomycetes are responsible for economically important
      losses in crops worldwide. Phytophthora palmivora, a tropical relative of the
      potato late blight pathogen, causes rotting diseases in many tropical crops
      including papaya, cocoa, oil palm, black pepper, rubber, coconut, durian, mango,
      cassava and citrus. Transcriptomics have helped to identify repertoires of host
      translocated microbial effector proteins which counteract defenses and reprogram
      the host in support of infection. As such, these studies have helped in
      understanding how pathogens cause diseases. Despite the importance of P.
      palmivora diseases, genetic resources to allow for disease resistance breeding
      and identification of microbial effectors are scarce. RESULTS: We employed the
      model plant Nicotiana benthamiana to study the P. palmivora root infections at
      the cellular and molecular levels. Time-resolved dual transcriptomics revealed
      different pathogen and host transcriptome dynamics. De novo assembly of P.
      palmivora transcriptome and semi-automated prediction and annotation of the
      secretome enabled robust identification of conserved infection-promoting
      effectors. We show that one of them, REX3, suppresses plant secretion processes.
      In a survey for early transcriptionally activated plant genes we identified a N.
      benthamiana gene specifically induced at infected root tips that encodes a
      peptide with danger-associated molecular features. CONCLUSIONS: These results
      constitute a major advance in our understanding of P. palmivora diseases and
      establish extensive resources for P. palmivora pathogenomics, effector-aided
      resistance breeding and the generation of induced resistance to Phytophthora root
      infections. Furthermore, our approach to find infection-relevant secreted genes
      is transferable to other pathogen-host interactions and not restricted to plants.

PMID- 28494762
TI  - The North American opioid epidemic: current challenges and a call for treatment
      as prevention.
AB  - There is a need for creative, public health-oriented solutions to the
      increasingly intractable problems associated with the North American opioid
      epidemic. This epidemic is a fundamentally continental problem, as routes of
      migration, drug demand, and drug exchange link the USA with Mexico and Canada.
      The challenges faced throughout North America include entrenched prescribing
      practices of opioid medications, high costs and low availability of medication
      assisted treatment (MAT), and policy approaches that present substantial barriers
      to care.We advocate for the scale up of a low-threshold treatment model for MAT
      that incorporates the best practices in addiction treatment. Such a model would
      remove barriers to care through widespread treatment availability and
      affordability and also a policy of decriminalization. Given that MAT reduces the
      frequency of drug injecting among opioid injectors, this treatment model should
      also be guided by an understanding of the socially communicable nature of
      injection drug use, such that increasing MAT availability may also prevent the
      spread of injecting practices to individuals at risk of transitions from non
      injection to injection drug use. To that end, the "Treatment as Prevention" model
      employed to respond to the individual- and population-level risks for HIV/AIDS
      prevention could be adapted to efforts to halt the North American opioid
      epidemic.

PMID- 28494761
TI  - Production of fuels and chemicals from xylose by engineered Saccharomyces
      cerevisiae: a review and perspective.
AB  - Efficient xylose utilization is one of the most important pre-requisites for
      developing an economic microbial conversion process of terrestrial
      lignocellulosic biomass into biofuels and biochemicals. A robust ethanol
      producing yeast Saccharomyces cerevisiae has been engineered with heterologous
      xylose assimilation pathways. A two-step oxidoreductase pathway consisting of
      NAD(P)H-linked xylose reductase and NAD+-linked xylitol dehydrogenase, and one
      step isomerase pathway using xylose isomerase have been employed to enable xylose
      assimilation in engineered S. cerevisiae. However, the resulting engineered yeast
      exhibited inefficient and slow xylose fermentation. In order to improve the yield
      and productivity of xylose fermentation, expression levels of xylose assimilation
      pathway enzymes and their kinetic properties have been optimized, and additional
      optimizations of endogenous or heterologous metabolisms have been achieved. These
      efforts have led to the development of engineered yeast strains ready for the
      commercialization of cellulosic bioethanol. Interestingly, xylose metabolism by
      engineered yeast was preferably respiratory rather than fermentative as in
      glucose metabolism, suggesting that xylose can serve as a desirable carbon source
      capable of bypassing metabolic barriers exerted by glucose repression.
      Accordingly, engineered yeasts showed superior production of valuable metabolites
      derived from cytosolic acetyl-CoA and pyruvate, such as 1-hexadecanol and lactic
      acid, when the xylose assimilation pathway and target synthetic pathways were
      optimized in an adequate manner. While xylose has been regarded as a sugar to be
      utilized because it is present in cellulosic hydrolysates, potential benefits of
      using xylose instead of glucose for yeast-based biotechnological processes need
      to be realized.

PMID- 28494764
TI  - Possible benefits of tomato juice consumption: a pilot study on irradiated human
      lymphocytes from healthy donors.
AB  - BACKGROUND: Reactive oxygen species (ROS) mediate much of the DNA damage caused
      by ionizing radiation. Among carotenoids, lycopene and beta-carotene, present in
      tomato juice, are known to be strong radical scavengers. The aim of the study was
      to investigate the effect of tomato juice intake on the levels of DNA damage and
      oxidative stress in human whole blood induced by in vitro exposure to X-rays.
      METHODS: Ten healthy adults were asked to drink 190 g of tomato juice, containing
      17 mg lycopene and 0.25 mg beta-carotene, per day for 3 weeks and then refrain
      from drinking it for 3 weeks. Peripheral whole blood samples were collected
      before and after the intake period of tomato juice and after the washout period.
      The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy.
      Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN)
      assay and the dicentrics (DIC) assay. The level of oxidative stress was
      determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma
      reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of
      carotenoids in plasma was measured at the three time points. RESULTS: The levels
      of 8-oxo-dG tended to decrease during the intake period and increase during the
      washout period. A non-significant inverse correlation was noted between the
      plasma concentration of lycopene plus beta-carotene and the level of 8-oxo-dG (P
      = 0.064). The radiation-induced MN and DIC frequencies increased in a dose
      dependent manner, and when compared at the same dose, the MN and DIC frequencies
      decreased during the intake period compared with those at baseline and then
      increased during the washout period. The results suggest that continuous tomato
      juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and
      MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG
      and d-ROMs. For most radiation doses, continuously tomato juice intake lowered
      the levels of MN and DIC. CONCLUSION: Tomato juice consumption may suppress human
      lymphocyte DNA damage caused by radiation, but further examination is required.
      TRIAL REGISTRATION: 2014-001 and 2014-R06.

PMID- 28494763
TI  - Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum
      isolates from Cambodia.
AB  - BACKGROUND: Artemisinin resistance is associated with delayed parasite clearance
      half-life in vivo and correlates with ring-stage survival under
      dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the
      PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and
      emerging piperaquine resistance in Southeast Asia show that artemisinin
      combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical
      effectiveness, prompting investigation of drug resistance mechanisms and
      development of strategies to surmount emerging anti-malarial resistance. METHODS:
      Sixty-eight parasites isolates with in vivo clearance data were obtained from two
      Tracking Resistance to Artemisinin Collaboration study sites in Cambodia, culture
      adapted, and genotyped for pfkelch13 and other mutations including pfmdr1 copy
      number; and the RSA0-3h survival rates and response to antimalarial drugs in
      vitro were measured for 36 of these isolates. RESULTS: Among these 36 parasites
      one isolate demonstrated increased ring-stage survival for a PfKelch13 mutation
      (D584V, RSA0-3h = 8%), previously associated with slow clearance but not yet
      tested in vitro. Several parasites exhibited increased ring-stage survival, yet
      lack pfkelch13 mutations, and one isolate showed evidence for piperaquine
      resistance. CONCLUSIONS: This study of 68 culture-adapted Plasmodium falciparum
      clinical isolates from Cambodia with known clearance values, associated the D584V
      PfKelch13 mutation with increased ring-stage survival and identified parasites
      that lack pfkelch13 mutations yet exhibit increased ring-stage survival. These
      data suggest mutations other than those found in pfkelch13 may be involved in
      conferring artemisinin resistance in P. falciparum. Piperaquine resistance was
      also detected among the same Cambodian samples, consistent with reports of
      emerging piperaquine resistance in the field. These culture-adapted parasites
      permit further investigation of mechanisms of both artemisinin and piperaquine
      resistance and development of strategies to prevent or overcome anti-malarial
      resistance.

PMID- 28494765
TI  - Duration of the common cold and similar continuous outcomes should be analyzed on
      the relative scale: a case study of two zinc lozenge trials.
AB  - BACKGROUND: The relative scale has been used for decades in analysing binary data
      in epidemiology. In contrast, there has been a long tradition of carrying out
      meta-analyses of continuous outcomes on the absolute, original measurement,
      scale. The biological rationale for using the relative scale in the analysis of
      binary outcomes is that it adjusts for baseline variations; however, similar
      baseline variations can occur in continuous outcomes and relative effect scale
      may therefore be often useful also for continuous outcomes. The aim of this study
      was to determine whether the relative scale is more consistent with empirical
      data on treating the common cold than the absolute scale. METHODS: Individual
      patient data was available for 2 randomized trials on zinc lozenges for the
      treatment of the common cold. Mossad (Ann Intern Med 125:81-8, 1996) found 4.0
      days and 43% reduction, and Petrus (Curr Ther Res 59:595-607, 1998) found 1.77
      days and 25% reduction, in the duration of colds. In both trials, variance in the
      placebo group was significantly greater than in the zinc lozenge group. The
      effect estimates were applied to the common cold distributions of the placebo
      groups, and the resulting distributions were compared with the actual zinc
      lozenge group distributions. RESULTS: When the absolute effect estimates, 4.0 and
      1.77 days, were applied to the placebo group common cold distributions, negative
      and zero (i.e., impossible) cold durations were predicted, and the high level
      variance remained. In contrast, when the relative effect estimates, 43 and 25%,
      were applied, impossible common cold durations were not predicted in the placebo
      groups, and the cold distributions became similar to those of the zinc lozenge
      groups. CONCLUSIONS: For some continuous outcomes, such as the duration of
      illness and the duration of hospital stay, the relative scale leads to a more
      informative statistical analysis and more effective communication of the study
      findings. The transformation of continuous data to the relative scale is simple
      with a spreadsheet program, after which the relative scale data can be analysed
      using standard meta-analysis software. The option for the analysis of relative
      effects of continuous outcomes directly from the original data should be
      implemented in standard meta-analysis programs.

PMID- 28494767
TI  - Intestinal differentiated mucinous adenocarcinoma of the endometrium with
      sporadic MSI high status: a case report.
AB  - BACKGROUND: Intestinal differentiation of primary mucinous adenocarcinoma of the
      uterine corpus is exceedingly rare in comparison to the approximately 25% rate in
      endocervical and ovarian mucinous carcinoma. Additionally, little is known about
      the related genetic and epigenetic alterations, even though large-scale molecular
      characterisation of the different types of endometrial cancer took place in the
      TCGA project along the entities defined by the recent WHO classification. CASE
      PRESENTATION: We present a 62-year-old patient harbouring a primary mucinous
      carcinoma of the uterine corpus with a morphological resemblance to mucinous
      colorectal adenocarcinoma. The intestinal differentiation was substantiated by
      CDX2 and CK20 positivity in the absence of PAX8, p16, WT1, p53, ER, PgR, AFP,
      SALL4 and Glypican3. A high MSI status with MLH1 hypermethylation was revealed by
      molecular testing. CONCLUSION: Intestinal differentiation of mucinous
      adenocarcinoma of the endometrium is a unique observation. Besides morphology, it
      obviously can share molecular features of sporadic MSI colorectal cancers. It can
      be speculated that either CDX2 positive morula formation or intestinal metaplasia
      of the endometrium as rare conditions might be the origin of carcinogenesis for
      this type II endometrial cancer. Both conditions were not detectable in this
      case. Of note, categorising endometrial cancers in genetic subgroups like MSI
      high cancers alone might lead to the integration of likewise morphologically
      different tumours like the case presented here with intestinal differentiation.
      Hence, careful genotype-phenotype correlations are warranted for studies of
      mucinous adenocarcinoma of the endometrium.

PMID- 28494769
TI  - Retraction Note: Anti-cancer effects of grailsine-al-glycoside isolated from
      Rhizoma Sparganii.

PMID- 28494766
TI  - FilmArrayTM GI panel performance for the diagnosis of acute gastroenteritis or
      hemorragic diarrhea.
AB  - BACKGROUND: Acute gastroenteritis is a common cause of morbidity and mortality in
      humans worldwide. The rapid and specific identification of infectious agents is
      crucial for correct patient management. However, diagnosis of acute
      gastroenteritis is usually performed with diagnostic panels that include only a
      few pathogens. In the present bicentric study, the diagnostic value of
      FilmArrayTM GI panels was assessed in unformed stool samples of patients with
      acute gastroenteritis and in a series of samples collected from pediatric
      patients with heamorragic diarrhea. The clinical performance of the FilmArrayTM
      gastrointestinal (GI) panel was assessed in 168 stool samples collected from
      patients with either acute gastroenteritis or hemorragic diarrhea. Samples
      showing discordant results between FilmArray and routine methods were further
      analyzed with an additional assay. RESULTS: Overall, the FilmArrayTM GI panel
      detected at least one potential pathogen in 92/168 (54.8%) specimens. In 66/92
      (71.8%) samples, only one pathogen was detected, while in 26/92 (28.2%) multiple
      pathogens were detected. The most frequent pathogens were rotavirus 13.9%
      (22/168), Campylobacter 10.7% (18/168), Clostridium difficile 9.5% (16/168), and
      norovirus 8.9% (15/168). Clostridium difficile was identified only in patients
      with acute gastroenteritis (p < 0.01), while STEC was detected exclusively in
      patients with hemorragic diarrhea (p < 0.01). In addition, Campylobacter spp.,
      Salmonella spp., EPEC and E. coli producing Shiga-like toxin were more frequently
      detected in patients with hemorragic diarrhea (p < 0.05). The overall percent
      agreement calculated in samples was 73.8% and 65.5%, while 34.5% were discordant.
      After additional confirmatory analyses, the proportion of discordant samples
      decreased to 7.7%. Rotavirus and astrovirus were the most frequently unconfirmed
      pathogens. CONCLUSION: In conclusion, the FilmArrayTM GI panel has proved to be a
      valuable new diagnostic tool for improving the diagnostic efficiency of GI
      pathogens.

PMID- 28494770
TI  - Exploring linkages between research, policy and practice in the Netherlands:
      perspectives on sexual and reproductive health and rights knowledge flows.
AB  - BACKGROUND: The attention to and demand for stronger linkages between research,
      policy and practice are increasing, especially in fields concerned with sensitive
      and challenging issues such as sexual and reproductive health and rights (SRHR).
      The study described in this article was conducted in the Netherlands among actors
      working in international development, especially the domain of SRHR. It explores
      the perceived flow of knowledge between research, policy and practice, the
      perceived impeding factors, and suggested strategies for improvement. METHODS: A
      narrative literature review was performed and 28 key informants were interviewed
      between May and August 2015. Most interviewees were either active or passive
      members of Share-Net Netherlands, an SRHR knowledge platform. All interviews,
      which lasted 70 minutes on average, were recorded, transcribed verbatim and coded
      in MAXQDA. RESULTS: Linkages between research, policy and practice are many and
      diffuse. The demands for and supplies of knowledge within and across the fields
      vary and do not always match, which is shown by participants' research purposes
      and approaches. Participants identified various barriers to strengthening
      knowledge flows, including a lack of familiarity with practices in other fields,
      power relations and the undervaluation of tacit knowledge. They suggested a more
      visible and concrete demand for and supply of knowledge, the development of a
      joint knowledge agenda, more opportunities for the interdisciplinary creation of
      knowledge, and the development of a system for learning and sharing knowledge.
      CONCLUSION: This study shows the willingness to undertake, and the perceived
      advantages of, interdisciplinary dialogues and joint creation of knowledge to
      advance SRHR research, policies and practices. Whereas barriers to the flow of
      knowledge may maintain present understandings of knowledge and of whose knowledge
      is valid, enabling factors, such as interactions between research, policy and
      practice in knowledge-sharing activities, may challenge such perceptions and
      create an enabling environment for generating innovative knowledge and increasing
      knowledge use. Knowledge platforms are recommended to place more emphasis on
      sharing and documenting tacit knowledge through interdisciplinary dialogues, to
      address power relations and to set criteria for interdisciplinary funding.

PMID- 28494771
TI  - Probable DRESS syndrome induced by IL-1 inhibitors.
AB  - Interleukin (IL)-1 inhibitors have been increasingly used for treating
      autoinflammatory diseases during the last 10 years, but the spectrum of their
      possible side effects is not yet fully known. Here, we bring physicians'
      attention to a new severe complication of IL-1 inhibitors, manifesting as a
      probable drug reaction with eosinophilia and systemic symptoms (DRESS) in two
      patients.

PMID- 28494768
TI  - Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002
      reduces neuroinflammation.
AB  - BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a
      key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS).
      Strategies that aim to inhibit leukocyte migration across the blood-brain barrier
      (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As
      the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in
      myeloid cells to induce inflammation and leukocyte trafficking, we explored the
      hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate
      neuro-inflammation. METHODS: Human monocytes were treated with a small molecule
      inhibitor (SMI) of CD40-TRAF6 interactions (6877002), and migration capacity
      across human brain endothelial cells was measured. To test the therapeutic
      potential of the CD40-TRAF6-blocking SMI under neuro-inflammatory conditions in
      vivo, Lewis rats and C57BL/6J mice were subjected to acute experimental
      autoimmune encephalomyelitis (EAE) and treated with SMI 6877002 for 6 days (rats)
      or 3 weeks (mice). RESULTS: We here show that a SMI of CD40-TRAF6 interactions
      (6877002) strongly and dose-dependently reduces trans-endothelial migration of
      human monocytes. Moreover, upon SMI treatment, monocytes displayed a decreased
      production of ROS, tumor necrosis factor (TNF), and interleukin (IL)-6, whereas
      the production of the anti-inflammatory cytokine IL-10 was increased. Disease
      severity of EAE was reduced upon SMI treatment in rats, but not in mice. However,
      a significant reduction in monocyte-derived macrophages, but not in T cells, that
      had infiltrated the CNS was eminent in both models. CONCLUSIONS: Together, our
      results indicate that SMI-mediated inhibition of the CD40-TRAF6 pathway skews
      human monocytes towards anti-inflammatory cells with reduced trans-endothelial
      migration capacity, and is able to reduce CNS-infiltrated monocyte-derived
      macrophages during neuro-inflammation, but minimally ameliorates EAE disease
      severity. We therefore conclude that SMI-mediated inhibition of the CD40-TRAF6
      pathway may represent a beneficial treatment strategy to reduce monocyte
      recruitment and macrophage activation in the CNS and has the potential to be used
      as a co-treatment to combat MS.

PMID- 28494772
TI  - Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer.
AB  - Targeted therapy and immunotherapy have revolutionized treatment of various
      cancers in the past decade. Despite targeted therapy with trastuzumab in Her2
      positive gastric cancer patients, survival has been dismal, mostly due to disease
      progression and toxicity related to the treatments. One area of active
      development is looking for ideal monoclonal antibodies (IMAB) specific to the
      proteins only on the tumor and hence avoiding unnecessary side effects. Claudin
      proteins with isoform 2 are one such protein, specific for several cancers,
      particularly gastric cancer and its metastases, leading to the development of
      anti-claudin 18.2 specific antibody, claudiximab. This review will highlight the
      latest development of claudiximab as first in class IMAB for the treatment of
      gastric cancer.

PMID- 28494773
TI  - Domains of quality of life freely expressed by cancer patients and their
      caregivers: contribution of the SEIQoL.
AB  - BACKGROUND: The purposes of this study, performed on a large sample of cancer
      patient-caregiver dyads, were: i) to simultaneously investigate, using an
      individualized quality of life (QoL) measure (Schedule for the Evaluation of
      Individual QoL, SEIQoL), the QoL domains freely expressed by cancer patients and
      their caregivers, and ii) to explore overlapping between the SEIQoL assessment
      and QoL assessment using traditional instruments. METHODS: The study employed a
      cross-sectional design including cancer patients who were going to receive
      chemotherapy treatment and their caregivers. Quality of life was assessed using
      condition-specific questionnaires (EORTC QLQ-C30 and CarGOQoL), generic health
      related questionnaire (SF-36), and open individualized measure (SEIQoL). RESULTS:
      The final sample included 205 patient-caregiver dyads. From the SEIQoL, Family,
      Health, and Leisures were the most freely expressed QoL domains by patients and
      caregivers, but reported with different weights. Love life and financial issues
      were less spontaneously mentioned. The SEIQoL index was moderately correlated to
      the condition-specific QoL questionnaires (R lower than |0.40|) and to SF-36
      (correlation coefficients: R ranging from 0.17 to 0.31). CONCLUSION:
      Individualized QoL measures allow individuals to spontaneously express important,
      non-predefined domains. This study highlights the need to explore QoL using a
      combination of individualized questionnaires and standardized questionnaires,
      capturing complementary facets that patients consider important in their life.

PMID- 28494774
TI  - Expanding conceptualizations of harm reduction: results from a qualitative
      community-based participatory research study with people who inject drugs.
AB  - BACKGROUND: The perspectives of people who use drugs are critical in
      understanding why people choose to reduce harm in relation to drug use, what
      practices are considered or preferred in conceptualizations of harm reduction,
      and which environmental factors interfere with or support the use of harm
      reduction strategies. This study explores how people who inject drugs (PWID)
      think about harm reduction and considers the critical imperative of equity in
      health and social services delivery for this community. METHODS: This community
      based participatory research study was conducted in a Canadian urban centre.
      Using a peer-based recruitment and interviewing strategy, semi-structured
      qualitative interviews were conducted by and with PWID. The Vidaview Life Story
      Board, an innovative tool where interviewers and participant co-construct a
      visual "life-scape" using a board, markers, and customized picture magnets, was
      used to facilitate the interviews. The topics explored included injection drug
      use and harm reduction histories, facilitators and barriers to using harm
      reduction strategies, and suggestions for improving services and supports.
      RESULTS: Twenty-three interviews with PWID (14 men and 9 women) were analysed,
      with a median age of 50. Results highlighted an expanded conceptualization of
      harm reduction from the perspectives of PWID, including motivations for adopting
      harm reduction strategies and a description of harm reduction practices that went
      beyond conventional health-focused concerns. The most common personal practices
      that PWID used included working toward moderation, employing various cognitive
      strategies, and engaging in community activities. The importance of social or
      peer support and improving self-efficacy was also evident. Further, there was a
      call for less rigid eligibility criteria and procedures in health and social
      services, and the need to more adequately address the stigmatization of drug
      users. CONCLUSIONS: These findings demonstrated that PWID incorporate many
      personal harm reduction practices in their daily lives to improve their well
      being, and these practices highlight the importance of agency, self-care, and
      community building. Health and social services are needed to better support these
      practices because the many socio-structural barriers this community faces often
      interfere with harm reduction efforts. Finally, "one size does not fit all" when
      it comes to harm reduction, and more personalized or de-medicalized
      conceptualizations are recommended.

PMID- 28494775
TI  - Gender blind? An analysis of global public-private partnerships for health.
AB  - BACKGROUND: The Global Public Private Partnerships for Health (GPPPH) constitute
      an increasingly central part of the global health architecture and carry both
      financial and normative power. Gender is an important determinant of health
      status, influencing differences in exposure to health determinants, health
      behaviours, and the response of the health system. We identified 18 GPPPH -
      defined as global institutions with a formal governance mechanism which includes
      both public and private for-profit sector actors - and conducted a gender
      analysis of each. RESULTS: Gender was poorly mainstreamed through the
      institutional functioning of the partnerships. Half of these partnerships had no
      mention of gender in their overall institutional strategy and only three
      partnerships had a specific gender strategy. Fifteen governing bodies had more
      men than women - up to a ratio of 5:1. Very few partnerships reported sex
      disaggregated data in their annual reports or coverage/impact results. The
      majority of partnerships focused their work on maternal and child health and
      infectious and communicable diseases - none addressed non-communicable diseases
      (NCDs) directly, despite the strong role that gender plays in determining risk
      for the major NCD burdens. CONCLUSIONS: We propose two areas of action in
      response to these findings. First, GPPPH need to become serious in how they "do"
      gender; it needs to be mainstreamed through the regular activities, deliverables
      and systems of accountability. Second, the entire global health community needs
      to pay greater attention to tackling the major burden of NCDs, including
      addressing the gendered nature of risk. Given the inherent conflicts of interest
      in tackling the determinants of many NCDs, it is debatable whether the emergent
      GPPPH model will be an appropriate one for addressing NCDs.

PMID- 28494776
TI  - Aggregated N-of-1 trials for unlicensed medicines for small populations: an
      assessment of a trial with ephedrine for myasthenia gravis.
AB  - BACKGROUND: Inexpensive medicines with a long history of use may currently be
      prescribed off-label for rare indications. Reimbursement is at the discretion of
      health insurance companies, and may be unpredictable. The example addressed was
      ephedrine as add-on treatment for myasthenia gravis. Stakeholders from academia,
      a patient organization, the Dutch National Health Care Institute (NHCI) and Dutch
      Medicines Evaluation Board (MEB) advised on the trial design. The NHCI and MEB
      agreed to provide scientific advice on the suitability of the evidence generated
      by the trial, for regulatory decisions. This paper describes the feasibility of
      the trial and the utility of its aggregated results. RESULTS: The trialists
      experienced the trial as feasible. Retrospective interviews showed that the trial
      as performed was acceptable to patients. The treatment effect in the primary
      outcome measure, muscle strength, was statistically significant when inferred to
      the population level, though the effect size was modest. Secondary outcomes were
      statistically significant in a preplanned, fixed effects analysis within the four
      patients. The NHCI advised that it could potentially make reimbursement decisions
      based on the Fitting Evidence framework, should the trialists decide to apply for
      reimbursement. The MEB advised that for a licensing decision, the N-of-1 design
      is a last-resort option for demonstrating treatment benefit in a rare disease. N
      of-1 trials alone do not provide enough evidence on potential risk. The MEB found
      the current trial inconclusive. It suggested doing a 2-armed trial of longer
      duration, possibly with a different outcome measure (postponement of
      corticosteroid use). It suggested engaging a consultancy or commercial sponsor,
      should the trialists decide to seek market authorization of the drug.
      CONCLUSIONS: In theory, evidence from aggregated N-of-1 trials is suitable for
      use in licensing and reimbursement decisions. The current example illustrates
      differences in interpretation of N-of-1 results by health authorities. In the era
      of personalized medicine, consensus is required on the interpretation of data
      from study designs geared to small groups. Demonstrating effectiveness of
      inexpensive medicines in small populations may require involvement of non
      commercial parties, to preserve affordability.

PMID- 28494777
TI  - Platelet desialylation is a novel mechanism and a therapeutic target in
      thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled
      trial.
AB  - BACKGROUND: Studies in murine models suggested that platelet desialylation was an
      important mechanism of thrombocytopenia during sepsis. METHODS: First, we
      performed a prospective, multicenter, observational study that enrolled septic
      patients with or without thrombocytopenia to determine the association between
      platelet desialylation and thrombocytopenia in patients with sepsis, severe
      sepsis, and septic shock. Gender- and age-matched healthy adults were selected as
      normal controls in analysis of the platelet desialylation levels (study I). Next,
      we conducted an open-label randomized controlled trial (RCT) in which the
      patients who had severe sepsis with thrombocytopenia (platelet counts <=50 *
      109/L) were randomly assigned to receive antimicrobial therapy alone (control
      group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1
      ratio (study II). The primary outcomes were platelet desialylation level at study
      entry, overall platelet response rate within 14 days post-randomization, and all
      cause mortality within 28 days post-randomization. Secondary outcomes included
      platelet recovery time, the occurrence of bleeding events, and the amount of
      platelets transfused within 14 days post-randomization. RESULTS: The platelet
      desialylation levels increased significantly in the 127 septic patients with
      thrombocytopenia compared to the 134 patients without thrombocytopenia. A
      platelet response was achieved in 45 of the 54 patients in the oseltamivir group
      (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P =
      0.045). The median platelet recovery time was 5 days (interquartile range 4-6) in
      the oseltamivir group compared with 7 days (interquartile range 5-10) in the
      control group (P = 0.003). The amount of platelets transfused decreased
      significantly in the oseltamivir group compared to the control group (P = 0.044).
      There was no difference in the overall 28-day mortality regardless of whether
      oseltamivir was used. The Sequential Organ Failure Assessment score and platelet
      recovery time were independent indicators of oseltamivir therapy. The main reason
      for all of the mortalities was multiple-organ failure. CONCLUSIONS:
      Thrombocytopenia was associated with increased platelet desialylation in septic
      patients. The addition of oseltamivir could significantly increase the platelet
      response rate, shorten platelet recovery time, and reduce platelet transfusion.
      TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .

PMID- 28494778
TI  - Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant
      phospholipid alterations in clear cell renal cell carcinoma.
AB  - BACKGROUND: The involvement of lipid metabolism in tumourigenesis and the
      progression of clear cell renal cell carcinoma (ccRCC) have been reported.
      However, the role of phospholipid profile alterations in ccRCC has not yet been
      systematically explored. In the present study, we compared the phospholipid
      compositions between ccRCC and paired normal renal tissues. METHODS: The
      phospholipid compositions of paired ccRCC and normal renal tissues were evaluated
      using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the
      mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which
      converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR,
      western blotting and immunohistochemistry were performed. The correlations of
      LPCAT1 expression with clinicopathological features and prognosis were assessed.
      In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines,
      and its effect on cell proliferation, cell cycle, migration and invasion were
      investigated. RESULTS: The phospholipid compositions of ccRCC and normal renal
      tissues were significantly different. Multiple LPC species were decreased and
      corresponding PC species were increased in cancer tissues. The mRNA and protein
      levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal
      tissues, and LPCAT1 expression was significantly correlated with unfavourable
      pathological features (higher tumour grade, higher TNM stage and larger tumour
      size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted
      PCs, inhibited cell proliferation, migration and invasion and induced cell cycle
      arrest at the G0/G1 phase. CONCLUSION: Selective changes in PC and LPC
      composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes
      the development and progression of ccRCC, likely through the conversion of LPC to
      PC.

PMID- 28494779
TI  - Blood homocysteine concentration and mood disorders with mixed features among
      patients with alcohol use disorder.
AB  - BACKGROUND: Blood homocysteine concentration (BHC) is higher in patients with
      alcohol use disorder (AUD). Previous studies have found a relationship between
      depressive symptoms severity and BHC in AUD patients and recently some authors
      have found high BHC among patients with bipolar disorder, both during manic and
      depressive episodes and in euthymic state. However, BHC in patients with mixed
      mood episode has not yet been investigated. The aim of this study was to evaluate
      the BHC of patients with AUD and mixed mood episode. METHODS: A sample of AUD
      outpatients was assessed by Mini-International Neuropsychiatric Interview (MINI
      Plus): those with a DSM-IV-TR mood disorder with mixed features were included in
      the MIXED group (n = 45), whereas those without mood episode were gathered in the
      NO MOOD group (n = 23). Two subgroups, MIXMANIA and MIXDEPRESSION, were formed
      according to the prevalence of manic or depressive symptoms, assessed by Young
      Mania Rating Scale (YMRS), and Hamilton Rating Scale for Depression (HDRS). The
      Alcohol Use Disorder Identification Test (AUDIT) was used to appraise the AUD.
      BHC was determined by High-Performance Liquid Chromatography. RESULTS: The MIXED
      group showed greater severity of both depressive (26.35 +/- 9.96 vs. 4.77 +/-
      0.92; p < 0.001) and manic (22.35 +/- 3.30 vs. 6.14 +/- 1.12; p < 0.001)
      symptoms, and higher BHC (28.80 +/- 11.47 vs. 10.83 +/- 2.81; p < 0.001), than
      the NO MOOD group. BHC was strongly correlated to the HDRS, YMRS and AUDIT
      scores, just as HDRS was to YMRS, and AUDIT was to both HDRS and YMRS, in the
      MIXED group only (p < 0.001). The MIXDEPRESSION subgroup showed higher BHC than
      the MIXMANIA subgroup (Mdn = 42.96, IQR = 10.44 vs. Mdn = 19.77, IQR = 5.93; p <
      0.001). A linear regression model conducted on the MIXED group found a
      significant predictive value for BHC of both HDRS (beta = 0.560, t = 2.43, p =
      0.026) and AUDIT (beta = 0.348, t = 2.17, p = 0.044). CONCLUSIONS: Depressive
      symptoms seem to be mainly implicated in the BHC elevation among patients with
      both mixed features mood disorder and AUD.

PMID- 28494780
TI  - Metastatic non-muscle invasive bladder cancer with meningeal carcinomatosis: case
      report of an unexpected response.
AB  - BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) is usually treated with
      local therapy including transurethral resection of the bladder tumor and
      intravesical therapy depending on the stage of the tumor. NMIBC is a rarely a
      metastatic diseases with lymph node invasion in less of 10%. In the other hand
      meningeal carcinomatosis is a rare location for metastases with extremely poor
      outcomes. We described a case report of a patient presenting a metastatic disease
      to bones and meninges, several years after the treatment of NMIBC, which had been
      in complete response (CR) for 4 years after chemotherapy treatment. CASE
      PRESENTATION: A 63-years old men was treated by TURBT in 2008 for a high grade
      NMIBC, pT1b. Three years later he presented an acute binocular diplopy with right
      trochlear nerve paralysis, and labial hypoesthesia. Brain scan and MRI were
      performed finding a clivus infiltration and a pachymeningitis. A vertebral biopsy
      was performed finding an invasive carcinoma, CK7+/CK20+, TTF1-, PSA-,
      Thyroglobulin- and GATA3+. The metastatic event was in relation to the high grade
      NMIBC treated 3 years previously. Palliative chemotherapy was started with
      cisplatin gemcitabine. After 6 cycles and to date, 4 years later, the patient is
      therefore considered in complete response. CONCLUSION: Metastasis in non-muscle
      invasive urothelial carcinoma is rare. Meningeal carcinomatosis outcome is poor,
      usually appearing in widely metastatic and progressive cancers but also because
      most systemic agents fail to pass the blood-brain barrier and penetrate into the
      cerebrospinal fluid. We described an unexpected response with complete response
      after chemotherapy for meningeal carcinomatosis of non muscle invasive urothelial
      carcinoma.

PMID- 28494781
TI  - Preparation and characterization of small-diameter decellularized scaffolds for
      vascular tissue engineering in an animal model.
AB  - BACKGROUND: The development of a suitable extracellular matrix (ECM) scaffold is
      the first step in vascular tissue engineering (VTE). Synthetic vascular grafts
      are available as an alternative to autologous vessels in large-diameter arteries
      (>8 mm) and medium-diameter arteries (6-8 mm). In small-diameter vessels (<6 mm),
      synthetic vascular grafts are of limited use due to poor patency rates. Compared
      with a vascular prosthesis, natural tissue ECM has valuable advantages. Despite
      considerable progress in recent years, identifying an optimal protocol to create
      a scaffold for use in small-diameter (<6 mm) fully natural tissue-engineered
      vascular grafts (TEVG), remains elusive. Although reports on different
      decellularization techniques have been numerous, combination of and comparison
      between these methods are scarce; therefore, we have compared five different
      decellularization protocols for making small-diameter (<6 mm) ECM scaffolds and
      evaluated their characteristics relative to those of fresh vascular controls.
      RESULTS: The protocols differed in the choice of enzymatic digestion solvent, the
      use of non-ionic detergent, the durations of the individual steps, and UV
      crosslinking. Due to their small diameter and ready availability, rabbit arteria
      carotis were used as the source of the ECM scaffolds. The scaffolds were
      subcutaneously implanted in rats and the results were evaluated using various
      microscopy and immunostaining techniques. CONCLUSIONS: Our findings showed that a
      2 h digestion time with 1* EDTA, replacing non-ionic detergent with double
      distilled water for rinsing and the application of UV crosslinking gave rise to
      an ECM scaffold with the highest biocompatibility, lowest cytotoxicity and best
      mechanical properties for use in vivo or in situ pre-clinical research in VTE in
      comparison.

PMID- 28494782
TI  - Health workforce and governance: the crisis in Nigeria.
AB  - BACKGROUND: In Nigeria, several challenges have been reported within the health
      sector, especially in training, funding, employment, and deployment of the health
      workforce. We aimed to review recent health workforce crises in the Nigerian
      health sector to identify key underlying causes and provide recommendations
      toward preventing and/or managing potential future crises in Nigeria. METHODS: We
      conducted a scoping literature search of PubMed to identify studies on health
      workforce and health governance in Nigeria. A critical analysis, with extended
      commentary, on recent health workforce crises (2010-2016) and the health system
      in Nigeria was conducted. RESULTS: The Nigerian health system is relatively weak,
      and there is yet a coordinated response across the country. A number of health
      workforce crises have been reported in recent times due to several months'
      salaries owed, poor welfare, lack of appropriate health facilities and emerging
      factions among health workers. Poor administration and response across different
      levels of government have played contributory roles to further internal crises
      among health workers, with different factions engaged in protracted supremacy
      challenge. These crises have consequently prevented optimal healthcare delivery
      to the Nigerian population. CONCLUSIONS: An encompassing stakeholders' forum in
      the Nigerian health sector remain essential. The national health system needs a
      solid administrative policy foundation that allows coordination of priorities and
      partnerships in the health workforce and among various stakeholders. It is hoped
      that this paper may prompt relevant reforms in health workforce and governance in
      Nigeria toward better health service delivery in the country.

PMID- 28494783
TI  - Genome-wide association study confirm major QTL for backfat fatty acid
      composition on SSC14 in Duroc pigs.
AB  - BACKGROUND: Fatty acid composition contributes importantly to meat quality and is
      essential to the nutritional value of the meat. Identification of genetic factors
      underlying levels of fatty acids can be used to breed for pigs with healthier
      meat. The aim of this study was to conduct genome-wide association studies (GWAS)
      to identify QTL regions affecting fatty acid composition in backfat from the pig
      breeds Duroc and Landrace. RESULTS: Using data from the Axiom porcine 660 K
      array, we performed GWAS on 454 Duroc and 659 Landrace boars for fatty acid
      phenotypes measured by near-infrared spectroscopy (NIRS) technology (C16:0,
      C16:1n-7, C18:0, C18:1n-9, C18:2n-6, C18:3n-3, total saturated fatty acids,
      monounsaturated fatty acids and polyunsaturated fatty acids). Two QTL regions on
      SSC4 and SSC14 were identified in Duroc for the de novo synthesized fatty acids
      traits, whereas one QTL on SSC8 was detected in Landrace for C16:1n-7. The QTL
      region on SSC14 has been reported in previous studies and a putative causative
      mutation has been suggested in the promoter region of the SCD gene. Whole genome
      re-sequencing data was used for genotype imputation and to fine map the SSC14 QTL
      region in Norwegian Duroc. This effort confirms the location of the QTL on this
      chromosome as well as suggesting other putative candidate genes in the region.
      The most significant single nucleotide polymorphisms (SNPs) located on SSC14
      explain between 55 and 76% of the genetic variance and between 27 and 54% of the
      phenotypic variance for the de novo synthesized fatty acid traits in Norwegian
      Duroc. For the QTL region on SSC8 in Landrace, the most significant SNP explained
      19% of the genetic variance and 5% of the phenotypic variance for C16:1n-7.
      CONCLUSIONS: This study confirms a major QTL affecting fatty acid composition on
      SSC14 in Duroc, which can be used in genetic selection to increase the level of
      fatty acid desaturation. The SSC14 QTL was not segregating in the Landrace
      population, but another QTL on SSC8 affecting C16:1n-7 was identified and might
      be used to increase the level of desaturation in meat products from this breed.

PMID- 28494784
TI  - Influence of neoadjuvant chemotherapy on prognosis of patients with synovial
      sarcoma.
AB  - BACKGROUND: This study aimed to explore the clinical efficacy of neoadjuvant
      chemotherapy combined with surgery in primary synovial sarcoma of the limbs and
      trunk through retrospective analysis of patients with primary synovial sarcoma of
      the limbs and trunk treated by this treatment in our hospital. METHODS: A total
      of 89 patients diagnosed with synovial sarcoma were enrolled in this study
      between January 2005 and December 2011 in PLA General Hospital. Most of the
      patients received neoadjuvant chemotherapy combined with operative treatment
      (84.3%), 10.1% of them received adjuvant chemotherapy combined with operative
      treatment, and only 5.6% received merely operative treatment. The influence on
      the prognosis of patients with synovial sarcoma was analyzed by the statistics
      overall survival (OS), progression-free survival (PFS), local control (LC), and
      freedom from distant metastasis (FFDM). RESULTS: The median follow-up time was
      68.6 months. The 5-year OS, 5-year PFS, 5-year LC, and 5-year FFDM of the
      patients were 80.2, 60.5, 78.8, and 80.8%, respectively. The OS of the patients
      with a tumor size >5 cm was lower (91.4 vs 73.1%, P < 0.05). Besides, the OS and
      FFDM of neoadjuvant chemotherapy were better than those of adjuvant chemotherapy
      (84.5 vs 55.6%, P = 0.015, and 83.8 vs 55.6%, P = 0.028, respectively). However,
      there was no significant difference in the LC and PFS. CONCLUSIONS: Neoadjuvant
      chemotherapy was beneficial for patients with synovial sarcoma, and it could
      improve survival time and control distant metastasis. Tumor size was an important
      factor influencing patients' prognosis.

PMID- 28494785
TI  - Assessing pre- and postoperative activity levels with an accelerometer: a proof
      of concept study.
AB  - BACKGROUND: Postoperative recovery after abdominal surgery is measured mostly
      based on subjective or self-reported data. In this article we aim to evaluate
      whether recovery of daily physical activity levels can be measured
      postoperatively with the use of an accelerometer. METHODS: In this multicenter,
      observational pilot study, 30 patients undergoing laparoscopic abdominal surgery
      (hysterectomy, adnexal surgery, cholecystectomy and hernia inguinal surgery) were
      included. Patients were instructed to wear an Actigraph wGT3X-BT accelerometer
      during one week before surgery (baseline) and during the first, third and fifth
      week after surgery. Wear time, steps taken and physical activity intensity levels
      (sedentary, light, moderate and vigorous) were measured. Patients were blinded
      for the accelerometer outcomes. Additionally, an activity diary comprising
      patients' self-reported time of being recovered and a list of 18 activities, in
      which the dates of resumption of these 18 activities were recorded after surgery,
      was completed by the patient. RESULTS: Five patients were excluded from analyses
      because of technical problems with the accelerometer (n = 1) and protocol non
      adherence (n = 4). Light, moderate, vigorous, combined moderate and vigorous
      intensity physical activity (MVPA), and step counts showed a clear recovery curve
      after surgery. Patients who underwent minor surgery reached their baseline step
      count and MVPA three weeks after surgery. Patients who underwent intermediate
      surgery had not yet reached their baseline step count during the last measuring
      week (five weeks after surgery). The results of the activity diaries showed a
      fair agreement with the accelerometer results (Cohens Kappa range: 0.273-0.391).
      Wearing the accelerometer was well tolerated and not regarded as being burdensome
      by the patients. CONCLUSIONS: The accelerometer appeared to be a feasible way to
      measure recovery of postoperative physical activity levels in this study and was
      well tolerated by the patients. The agreement with self-reported physical
      recovery times was fair.

PMID- 28494787
TI  - Missing heritability and where to find it.
AB  - A report on the 11th Genomics of Rare Disease meeting held at the Wellcome Genome
      Campus, Hinxton, Cambridge, UK, 5-7 April, 2017.

PMID- 28494786
TI  - Compositionally and functionally distinct sinus microbiota in chronic
      rhinosinusitis patients have immunological and clinically divergent consequences.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized
      by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of
      this heterogeneity is poorly understood. We sought to address the hypothesis that
      a limited number of compositionally distinct pathogenic bacterial microbiota
      exist in CRS patients and invoke discrete immune responses and clinical
      phenotypes in CRS patients. RESULTS: Sinus brushings from patients with CRS (n =
      59) and healthy individuals (n = 10) collected during endoscopic sinus surgery
      were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA
      profiling of the mucosal immune response. We show that CRS patients cluster into
      distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co
      colonization (permutational multivariate analysis of variance (PERMANOVA); p =
      0.001, r 2 = 0.318). Each sub-group was typically dominated by a pathogenic
      family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae
      [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was
      predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2 = 0.217) and
      encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI),
      tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR
      gamma signaling pathway [DSIII(a)]. Each is also associated with significantly
      distinct host immune responses; DSI, II, and III(b) invoked a variety of pro
      inflammatory, TH1 responses, while DSIII(a), which exhibited significantly
      increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk =
      2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045).
      CONCLUSIONS: A large proportion of CRS patient heterogeneity may be explained by
      the composition of their sinus bacterial microbiota and related host immune
      response-features which may inform strategies for tailored therapy in this
      patient population.

PMID- 28494788
TI  - Comprehensive analysis of treatment response phenotypes in rheumatoid arthritis
      for pharmacogenetic studies.
AB  - BACKGROUND: An individual patient's response to a particular drug is influenced
      by multiple factors, which may include genetic predisposition. Pharmacogenetic
      studies attempt to discover and estimate the contributions of genetic variants to
      the variability in response to a drug treatment. The task of identifying the
      genetic contribution is often complicated by response phenotypes that are based
      on imprecise or subjective clinical observations. Because the success of a
      pharmacogenetic study depends on the analysis of a heritable phenotype, it is
      important to identify phenotypes with a significant heritable component to ensure
      reliable and reproducible results in subsequent genetic association studies.
      METHODS: We retrospectively analyzed data collected from 436 rheumatoid arthritis
      patients treated with golimumab during the phase III GO-FURTHER study. We
      investigated the reliability of several potential response outcomes after
      golimumab treatment. Using whole-genome sequencing of the clinical trial cohort,
      we estimated the heritability of each potential outcome measure. We further
      performed a longitudinal analysis of the clinical data to estimate variability of
      outcome measures over time and the degree to which each response metric could be
      confounded by placebo response. RESULTS: We determined that the high degree of
      within-patient variation over time makes a single follow-up visit insufficient to
      assess an individual patient's response to golimumab treatment. We found that
      different potential response outcomes had varying degrees of heritability and
      that averaging across multiple follow-up visits yielded higher heritability
      estimates than single follow-up estimates. Importantly, we found that the change
      in swollen and tender joint counts were the most heritable outcome metrics we
      tested; however, we showed that they are also more likely to be confounded by a
      placebo response than objective phenotypes like the change in C-reactive protein
      levels. CONCLUSIONS: Our rigorous approach to finding robust and heritable
      response phenotypes could be beneficial to all pharmacogenetic studies and may
      lead to more reliable and reproducible results. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00973479 . Registered 4 September 2009.

PMID- 28494789
TI  - microRNAs: important regulators of stem cells.
AB  - Stem cells are undifferentiated cells and have multi-lineage differentiation
      potential. Generally, stem cells are classified into adult stem cells, embryonic
      stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Stem cells have
      great potential in clinical therapy due to their pluripotency and self-renewal
      ability. microRNAs (miRNAs) are small non-coding RNAs which are evolutionarily
      conserved and participate in the pathogenesis of many diseases, cell cycle
      regulation, apoptosis, aging, cell fate decisions, and different signaling
      pathways. Different kinds of stem cells possess distinct miRNA expression
      profiles. Our review summarizes the critical roles of miRNAs in stem cell
      reprogramming, pluripotency maintenance, and differentiation. In the future,
      miRNAs may greatly contribute to stem cell clinical therapy and have potential
      applications in regenerative medicine.

PMID- 28494790
TI  - Erratum to: Keratinocyte growth factor in acute lung injury to reduce pulmonary
      dysfunction - a randomised placebo-controlled trial (KARE): study protocol.

PMID- 28494791
TI  - A cohort study examining emergency department visits and hospital admissions
      among people who use drugs in Ottawa, Canada.
AB  - BACKGROUND: The health of people who use drugs (PWUD) is characterized by
      multimorbidity and chronicity of health conditions, necessitating an
      understanding of their health care utilization. The objective of this study was
      to evaluate emergency department (ED) visits and hospital admissions among a
      cohort of PWUD. METHODS: We used a retrospective observational design between
      2012 and 2013. The population was a marginalized cohort of PWUD (the PROUD study)
      for whom survey data was linked (n = 663) to provincial health administrative
      data housed at the Institute for Clinical Evaluative Sciences. We constructed a
      5:1 comparison group matched by age, sex, income quintile, and region. The main
      outcomes were defined as having two or more ED visits, or one or more hospital
      admissions, in the year prior to survey completion. We used multivariable
      logistic regression analyses to identify factors associated with these outcomes.
      RESULTS: Compared to the matched cohort, PWUD had higher rates of ED visits (rate
      ratio [RR] 7.0; 95% confidence interval [95% CI] 6.5-7.6) and hospitalization (RR
      7.7; 95% CI 5.9-10.0). After adjustment, factors predicting more ED visits were
      receiving disability (adjusted odds ratio [AOR] 3.0; 95% CI 1.7-5.5) or income
      assistance (AOR 2.7; 95% CI 1.5-5.0), injection drug use (AOR 2.1; 95% CI 1.3
      3.4), incarceration within 12 months (AOR 1.6; 95% CI 1.1-2.4), mental health
      comorbidity (AOR 2.1; 95% CI 1.4-3.1), and a suicide attempt within 12 months
      (AOR 2.1; 95% CI 1.1-3.4). Receiving methadone (AOR 0.5; 95% CI 0.3-0.9) and
      having a regular family physician (AOR 0.5; 95% CI 0.2-0.9) were associated with
      lower odds of having more ED visits. Factors associated with more hospital
      admissions included Aboriginal identity (AOR 2.4; 95% CI 1.4-4.1), receiving
      disability (AOR 2.4; 95% CI 1.1-5.4), non-injection drug use (opioids and non
      opioids) (AOR 2.2; 95% CI 1.1-4.4), comorbid HIV (AOR 2.4; 95% CI 1.2-5.6),
      mental health comorbidity (AOR 2.4; 95% CI 1.3-4.2), and unstable housing (AOR
      1.9; 95% CI 1.0-3.4); there were no protective factors for hospitalization.
      CONCLUSIONS: Improved post-incarceration support, housing services, and access to
      integrated primary care services including opioid replacement therapy may be
      effective interventions to decrease acute care use among PWUD, including targeted
      approaches for people receiving social assistance or with mental health concerns.

PMID- 28494792
TI  - Heterosis as a consequence of regulatory incompatibility.
AB  - BACKGROUND: The merging of genomes in inter-specific hybrids can result in novel
      phenotypes, including increased growth rate and biomass yield, a phenomenon known
      as heterosis. Heterosis is typically viewed as the opposite of hybrid
      incompatibility. In this view, the superior performance of the hybrid is
      attributed to heterozygote combinations that compensate for deleterious mutations
      accumulating in each individual genome, or lead to new, over-dominating
      interactions with improved performance. Still, only fragmented knowledge is
      available on genes and processes contributing to heterosis. RESULTS: We describe
      a budding yeast hybrid that grows faster than both its parents under different
      environments. Phenotypically, the hybrid progresses more rapidly through cell
      cycle checkpoints, relieves the repression of respiration in fast growing
      conditions, does not slow down its growth when presented with ethanol stress, and
      shows increased signs of DNA damage. A systematic genetic screen identified
      hundreds of S. cerevisiae alleles whose deletion reduced growth of the hybrid.
      These growth-affecting alleles were condition-dependent, and differed greatly
      from alleles that reduced the growth of the S. cerevisiae parent. CONCLUSIONS:
      Our results define a budding yeast hybrid that is perturbed in multiple
      regulatory processes but still shows a clear growth heterosis. We propose that
      heterosis results from incompatibilities that perturb regulatory mechanisms,
      which evolved to protect cells against damage or prepare them for future
      challenges by limiting cell growth.

PMID- 28494793
TI  - Real-time PCR assays for hepatitis B virus DNA quantification may require two
      different targets.
AB  - BACKGROUND: Quantification Hepatitis B virus (HBV) DNA plays a critical role in
      the management of chronic HBV infections. However, HBV is a DNA virus with high
      levels of genetic variation, and drug-resistant mutations have emerged with the
      use of antiviral drugs. If a mutation caused a sequence mismatched in the primer
      or probe of a commercial DNA quantification kit, this would lead to an
      underestimation of the viral load of the sample. The aim of this study was to
      determine whether commercial kits, which use only one pair of primers and a
      single probe, accurately quantify the HBV DNA levels and to develop an improved
      duplex real-time PCR assay. METHODS: We developed a new duplex real-time PCR
      assay that used two pairs of primers and two probes based on the conserved S and
      C regions of the HBV genome. We performed HBV DNA quantitative detection of HBV
      samples and compared the results of our duplex real-time PCR assays with the
      COBAS TaqMan HBV Test version 2 and Daan real-time PCR assays. The target region
      of the discordant sample was amplified, sequenced, and validated using plasmid.
      RESULTS: The results of the duplex real-time PCR were in good accordance with the
      commercial COBAS TaqMan HBV Test version 2 and Daan real-time PCR assays. We
      showed that two samples from Chinese HBV infections underestimated viral loads
      when quantified by the Roche kit because of a mismatch between the viral sequence
      and the reverse primer of the Roche kit. The HBV DNA levels of six samples were
      undervalued by duplex real-time PCR assays of the C region because of mutations
      in the primer of C region. CONCLUSIONS: We developed a new duplex real-time PCR
      assay, and the results of this assay were similar to the results of commercial
      kits. The HBV DNA level could be undervalued when using the COBAS TaqMan HBV Test
      version 2 for Chinese HBV infections owing to a mismatch with the primer/probe. A
      duplex real-time PCR assay based on the S and C regions could solve this problem
      to some extent.

PMID- 28494794
TI  - Juvenile idiopathic arthritis in relation to perinatal and maternal
      characteristics: a case control study.
AB  - BACKGROUND: Existing data on associations between maternal and early childhood
      exposures and juvenile idiopathic arthritis (JIA) risk is scant and inconsistent
      with previous studies showing potential role for prematurity, number of siblings
      and infections. We explored JIA and International League of Associations for
      Rheumatology (ILAR) JIA categories in relation to selected infant (birthweight,
      size-for-gestational-age, gestational age), and maternal (parity, delivery type,
      prior fetal loss) characteristics that may be markers for exposures related to
      two pathways (hygiene hypothesis, microchimerism) potentially associated with
      autoimmune disorder occurrence. METHODS: A case-control analysis with 1,234 JIA
      cases and 5,993 birth year-matched controls was conducted. Exposure information
      was obtained from WA state birth certificates. Multivariable logistic regression
      was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI)
      for associations with maternal and early life exposures for JIA and JIA
      categories. RESULTS: Greater maternal parity was associated with a decreased OR
      for JIA (most marked for persistent oligoarticular JIA, OR 0.32, 95% CI 0.15;
      0.71, p for trend = 0.0001). Prior fetal loss (except for oligoarticular JIA) was
      associated with an increased OR for JIA. Prematurity was associated with
      increased risk of enthesitis related arthritis (OR 1.9, 95% CI: 1.3-2.9) and
      rheumatoid factor positive polyarticular JIA (OR 2.2, 95% CI: 1.0-4.8).
      CONCLUSIONS: We observed associations of selected maternal factors with JIA, some
      of which varied across JIA categories. The findings of decreased ORs for JIA in
      relation to greater maternal parity may be consistent with the hygiene and
      microchimerism hypotheses. Future studies with biomarkers relevant to these
      hypotheses will help elucidate any associations.

PMID- 28494795
TI  - A bio-behavioral intervention to decrease intravaginal practices and bacterial
      vaginosis among HIV infected Zambian women, a randomized pilot study.
AB  - BACKGROUND: Intravaginal practices (IVP) (cleansing or introducing products
      inside the vagina for hygiene, health or to please sexual partners) are common
      among women with HIV. IVP increase the risk of developing bacterial Vaginosis
      (BV), the most common genital infection associated with transmission of sexually
      transmitted infections and HIV. This study tested a pilot intervention to reduce
      IVP and BV in HIV infected women in Zambia. METHODS: One hundred twenty-eight HIV
      infected women engaging in IVP were randomized to two conditions: enhanced
      standard of care (n = 70) and experimental (n = 58) from May 1, 2013 to February
      28, 2014. All participants received a brief educational counseling session on
      discontinuation of IVP, and those with BV, were provided with medical treatment
      for BV. Women in the experimental condition received an additional group-based,
      culturally tailored intervention. Participants completed questionnaires assessing
      sexual risk factors and IVP and were assessed for BV using Nugent criteria at
      baseline, 6 months and 12 months. RESULTS: At 12-month, the proportion of self
      reported use of IVPs decreased in the experimental condition: soap (28% vs. 47%);
      cloth or a rag (19% vs. 38%); and traditional medicines (22% vs. 42%) (all p <
      0.05)) compared with the enhanced standard of care condition. The prevalence of
      BV at 6 and 12 months did not differ by study condition but averaging over study
      condition, prevalence of BV decreased from 64.2% at baseline to 15.6% at 6 months
      (p < 0.01) and to 23.6% at 12 months (p = 0.15). Using an enhanced standard of
      care approach and an enhanced standard of care + a group intervention, IVP and BV
      decreased over time, but the experimental condition had greater reduction in self
      reported use of IVP. CONCLUSIONS: Future studies should address interventions in
      communities with high burden of IVP, BV and HIV. Interventions that could be
      administered during routine medical care and decrease IVP and BV are needed, and
      should be considered part of women's health programs. TRIAL REGISTRATION NUMBER:
      NCT03134924 (retrospectively registered 21st April 2017).

PMID- 28494796
TI  - A malignant solitary fibrous tumour arising from the first lumbar vertebra and
      mimicking an osteosarcoma: a case report.
AB  - BACKGROUND: A solitary fibrous tumour (SFT) is an unusual neoplasm typically
      found in soft tissues. Although SFTs can arise in the bones, they very rarely
      arise in the vertebral arch. Here, we describe a case of a SFT that arose in the
      vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked
      osteosarcoma. CASE PRESENTATION: A 49-year-old woman presented with a 2-month
      history of lower back pain and a lumbar region mass. Magnetic resonance imaging
      demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The
      patient received neoadjuvant chemotherapy, followed by a surgical procedure
      comprising an anterior spinal fusion and en bloc resection. Histologically, our
      initial diagnosis was osteosarcoma. The postoperative course was uneventful, and
      the patient received adjuvant chemotherapy. However, the tumour metastasised to
      the lung 5 years after the first surgery, and a second surgery was performed for
      lung tumour resection. The histology of the metastatic lung tumour appeared
      similar to that of the malignant SFT, and the specimen from the first surgery was
      re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse
      transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus
      confirming our final diagnosis of malignant SFT. The patient died of disease
      progression 8 years after the first surgery; however, there was no evidence of
      local recurrence. CONCLUSIONS: Malignant SFT in the vertebral arch is extremely
      rare and very difficult to distinguish histologically an osteoid from lace-like
      collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from
      other neoplasms. Although it is difficult to completely resect a SFT arising from
      the spine, we demonstrated the feasibility of an en bloc resection of spinal
      tumours arising from posterior elements, without local recurrence.

PMID- 28494797
TI  - AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways
      in triple-negative breast cancer.
AB  - BACKGROUND: AHNAK, also known as desmoyokin, is a giant protein with the
      molecular size of approximately 700 kDa and exerts diverse functions in different
      types of cancer. RESULTS: In the present study, we demonstrated that AHNAK mRNA
      levels were down-regulated in 7 out of 8 human breast cancer cell lines,
      especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in
      patients with TNBC, the expression of AHNAK gene was inversely correlated with
      the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN)
      infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated
      AHNAK expression was considered an independent prognostic factor associated with
      the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell
      lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and
      colony formation, and inhibited the in vivo TNBC xenograft growth and lung
      metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the
      AKT/MAPK signaling pathway and Wnt/beta-catenin pathway. Consistent results were
      observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells. CONCLUSIONS:
      Taken together, our results suggest that AHNAK acts as a tumor suppressor that
      negatively regulates TNBC cell proliferation, TNBC xenograft growth and
      metastasis via different signaling pathways.

PMID- 28494798
TI  - Androstenedione response to recombinant human FSH is the most valid predictor of
      the number of selected follicles in polycystic ovarian syndrome: (a case-control
      study).
AB  - BACKGROUND: We aimed to test the hypothesis that the correlation of the changes
      in the blood Androstenedione (A4) levels to the number of selected follicles
      during ovulation induction with low-dose recombinant human follicle stimulating
      hormone (rhFSH) is as strong as the correlation to changes in the blood Estradiol
      (E2) levels in polycystic ovary syndrome (PCOS). METHODS: Prospective Case
      control study conducted from October 2014 to January 2016. 61 non-PCOS control
      (Group I) and 46 PCOS (Group II) patients treated with the chronic low-dose step
      up protocosl with rhFSH. A4, E2, progesterone blood levels and follicular growth
      were monitored.. Univariate and hierarchical multivariable analysis were
      performed for age, BMI, HOMA-IR, A4 and E2 (with the number of selected follicles
      as the dependent variable in both groups). ROC analysis was performed to define
      threshold values for the significant determinants of the number of selected
      follicles to predict cyle cancellations due to excessive ovarian response.
      RESULTS: The control group (Group I) was comprised of 61 cycles from a group of
      primary infertile non-PCOS patients, and the study group (Group II) of 46 cycles
      of PCOS patients. The analysis revealed that the strongest independent predictor
      of the total number of selected follicles in Group I was the E2(AUC) (B =
      0.0006[0.0003-0.001]; P < 0.001); whereas for Group II, it was the A4 (AUC) (B =
      0.114[0.04-0.25]; P = 0.01). Optimum thresholds for the A4 related parameters
      were defined to predict excessive response within Group II were 88.7%, 3.1 ng/mL
      and 5.4 ng*days for the percentage increase in A4, the maximum A4 value and area
      under the curve values for A4, respectively. CONCLUSION: A4 response to low-dose
      rhFSH in PCOS has a stronger association with the number of follicles selected
      than the E2 reponse. A4 response preceding the E2 response is essential for
      progressive follicle development. Monitoring A4 rather than E2 may be more
      preemptive to define the initial ovarian response and accurate titration of the
      rhFSH doses. TRIAL REGISTRATION: The study was registered as a prospective case
      control study in the ClinicalTrials.gov registry with the identifier NCT02329483
      .

PMID- 28494799
TI  - A systematic review of electronic audit and feedback: intervention effectiveness
      and use of behaviour change theory.
AB  - BACKGROUND: Audit and feedback is a common intervention for supporting clinical
      behaviour change. Increasingly, health data are available in electronic format.
      Yet, little is known regarding if and how electronic audit and feedback (e-A&F)
      improves quality of care in practice. OBJECTIVE: The study aimed to assess the
      effectiveness of e-A&F interventions in a primary care and hospital context and
      to identify theoretical mechanisms of behaviour change underlying these
      interventions. METHODS: In August 2016, we searched five electronic databases,
      including MEDLINE and EMBASE via Ovid, and the Cochrane Central Register of
      Controlled Trials for published randomised controlled trials. We included studies
      that evaluated e-A&F interventions, defined as a summary of clinical performance
      delivered through an interactive computer interface to healthcare providers. Data
      on feedback characteristics, underlying theoretical domains, effect size and risk
      of bias were extracted by two independent review authors, who determined the
      domains within the Theoretical Domains Framework (TDF). We performed a meta
      analysis of e-A&F effectiveness, and a narrative analysis of the nature and
      patterns of TDF domains and potential links with the intervention effect.
      RESULTS: We included seven studies comprising of 81,700 patients being cared for
      by 329 healthcare professionals/primary care facilities. Given the extremely high
      heterogeneity of the e-A&F interventions and five studies having a medium or high
      risk of bias, the average effect was deemed unreliable. Only two studies
      explicitly used theory to guide intervention design. The most frequent
      theoretical domains targeted by the e-A&F interventions included 'knowledge',
      'social influences', 'goals' and 'behaviour regulation', with each intervention
      targeting a combination of at least three. None of the interventions addressed
      the domains 'social/professional role and identity' or 'emotion'. Analyses
      identified the number of different domains coded in control arm to have the
      biggest role in heterogeneity in e-A&F effect size. CONCLUSIONS: Given the high
      heterogeneity of identified studies, the effects of e-A&F were found to be highly
      variable. Additionally, e-A&F interventions tend to implicitly target only a
      fraction of known theoretical domains, even after omitting domains presumed not
      to be linked to e-A&F. Also, little evaluation of comparative effectiveness
      across trial arms was conducted. Future research should seek to further unpack
      the theoretical domains essential for effective e-A&F in order to better support
      strategic individual and team goals.

PMID- 28494800
TI  - Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune
      responses in ovalbumin-induced airway inflammation in BALB/c mice.
AB  - BACKGROUND: Recently the role of gastrointestinal nematodes in modulating the
      immune responses in inflammatory and immune-mediated conditions such as allergy
      and autoimmune diseases has been introduced. This is mainly due to the
      suppressive effects of somatic and excretory secretory (ES) products of nematodes
      on the immune responses. In this study, we evaluated the immunomodulatory
      potentials of somatic products of Marshallagia marshalli, a gastrointestinal
      nematodes of sheep, to suppress the immune-mediated responses in a murine model
      of allergic airway inflammation. BALB/c mice were intraperitoneally (IP)
      sensitized with ovalbumin (OVA)/Alum and then challenged with 1% OVA. Somatic
      products of M. marshalli were administered during each sensitization. The effects
      of somatic products on development of allergic airway inflammation were evaluated
      by analyzing inflammatory cells recruitment, histopathological changes, cytokines
      production (IL-4, IL-13, IL-10, TGF-beta) and serum antibody titers (IgG1,
      IgG2a). RESULTS: Somatic products of M. marshalli were able to suppress the
      induction of allergic airway inflammation in mice. Modulation of Th2 type
      responses (IL-4, IL-13, IgG1) via upregulations of IL-10 and TGF-beta production
      was observed after injection of somatic products of M. marshalli. In addition,
      inflammatory cells infiltration and pathological disorders were significantly
      diminished following administration of somatic products. CONCLUSIONS: Our data
      raised the possibility that helminths could be a potential therapeutic candidate
      to alleviate the inflammatory conditions in allergic asthma. According to these
      results, we concluded that M. marshalli may contain immune-modulatory molecules
      that attenuate allergic airway inflammation via induction of regulatory
      cytokines. Further investigations are required to identify molecules that might
      have potentials for development of novel therapeutic targets.

PMID- 28494801
TI  - Spectral imaging toolbox: segmentation, hyperstack reconstruction, and batch
      processing of spectral images for the determination of cell and model membrane
      lipid order.
AB  - BACKGROUND: Spectral imaging with polarity-sensitive fluorescent probes enables
      the quantification of cell and model membrane physical properties, including
      local hydration, fluidity, and lateral lipid packing, usually characterized by
      the generalized polarization (GP) parameter. With the development of commercial
      microscopes equipped with spectral detectors, spectral imaging has become a
      convenient and powerful technique for measuring GP and other membrane properties.
      The existing tools for spectral image processing, however, are insufficient for
      processing the large data sets afforded by this technological advancement, and
      are unsuitable for processing images acquired with rapidly internalized
      fluorescent probes. RESULTS: Here we present a MATLAB spectral imaging toolbox
      with the aim of overcoming these limitations. In addition to common operations,
      such as the calculation of distributions of GP values, generation of pseudo
      colored GP maps, and spectral analysis, a key highlight of this tool is reliable
      membrane segmentation for probes that are rapidly internalized. Furthermore,
      handling for hyperstacks, 3D reconstruction and batch processing facilitates
      analysis of data sets generated by time series, z-stack, and area scan microscope
      operations. Finally, the object size distribution is determined, which can
      provide insight into the mechanisms underlying changes in membrane properties and
      is desirable for e.g. studies involving model membranes and surfactant coated
      particles. Analysis is demonstrated for cell membranes, cell-derived vesicles,
      model membranes, and microbubbles with environmentally-sensitive probes Laurdan,
      carboxyl-modified Laurdan (C-Laurdan), Di-4-ANEPPDHQ, and Di-4-AN(F)EPPTEA (FE),
      for quantification of the local lateral density of lipids or lipid packing.
      CONCLUSIONS: The Spectral Imaging Toolbox is a powerful tool for the segmentation
      and processing of large spectral imaging datasets with a reliable method for
      membrane segmentation and no ability in programming required. The Spectral
      Imaging Toolbox can be downloaded from
      https://uk.mathworks.com/matlabcentral/fileexchange/62617-spectral-imaging
      toolbox .

PMID- 28494802
TI  - Reducing depressive symptomatology with a smartphone app: study protocol for a
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Depression has become one of the leading contributors to the global
      disease burden. Evidence-based treatments for depression are available, but
      access to them is still limited in some instances. As technology has become more
      integrated into mental health care, computerized cognitive behavioral therapy
      (CBT) protocols have become available and have been recently transposed to mobile
      environments (e.g., smartphones) in the form of "apps." Preliminary research on
      some depression apps has shown promising results in reducing subthreshold or mild
      to moderate depressive symptoms. However, this small number of studies reports a
      low statistical power and they have not yet been replicated. Moreover, none of
      them included an active placebo comparison group. This is problematic, as a
      "digital placebo effect" may explain some of the positive effects documented
      until now. The aim of this study is to test a newly developed mobile app firmly
      grounded in the CBT theory of depression to determine whether this app is
      clinically useful in decreasing moderate depressive symptoms when compared with
      an active placebo. Additionally, we are interested in the app's effect on
      emotional wellbeing and depressogenic cognitions. METHODS/DESIGN: Romanian
      speaking adults (18 years and older) with access to a computer and the Internet
      and owning a smartphone are included in the study. A randomized, three-arm
      clinical trial is being conducted (i.e., active intervention, placebo
      intervention and delayed intervention). Two hundred and twenty participants with
      moderate depressive symptoms (i.e., obtaining scores >9 and <=16 on the Patient
      Health Questionnaire, PHQ-9) will be randomized to the three conditions.
      Participants undergoing therapy, presenting serious mental health problems, or
      legal or health issues that would prevent them from using the app, as well as
      participants reporting suicidal ideation are excluded. Participants randomized to
      the active and placebo interventions will use the smartphone app for 6 weeks. A
      short therapist check-in via phone will take place every week. Participants in
      the delayed-intervention condition will be given access to the app after 6 weeks
      from randomization. The primary outcome is the level of depressive
      symptomatology. The intervention delivered through the app to the active
      condition includes psychoeducational materials and exercises based on CBT for
      depression, while the placebo intervention uses a sham version of the app (i.e.,
      similar structure of courses and exercises). DISCUSSION: To our knowledge, this
      study protocol is the first to test the efficacy of a smartphone app for
      depressive symptomatology in the form of a randomized controlled trial (RCT) that
      includes an active placebo condition. As such, this can substantially add to the
      body of evidence supporting the use of apps designed to decrease depression.
      TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03060200 . Registered on 1
      February 2017. The first participant was enrolled on 17 February 2017.

PMID- 28494803
TI  - Alzheimer's disease, dementia, and stem cell therapy.
AB  - Alzheimer's disease (AD) represents arguably the most significant social,
      economic, and medical crisis of our time. Characterized by progressive
      neurodegenerative pathology, AD is first and foremost a condition of neuronal and
      synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by
      exogenous stem cells is therefore a rational therapeutic strategy. This review
      will focus on recent advances in stem cell therapies utilizing animal models of
      AD, as well as detailing the human clinical trials of stem cell therapies for AD
      that are currently undergoing development.

PMID- 28494804
TI  - Validity of the posttraumatic stress disorders (PTSD) checklist in pregnant
      women.
AB  - BACKGROUND: The PTSD Checklist-civilian (PCL-C) is one of the most commonly used
      self-report measures of PTSD symptoms, however, little is known about its
      validity when used in pregnancy. This study aims to evaluate the reliability and
      validity of the PCL-C as a screen for detecting PTSD symptoms among pregnant
      women. METHODS: A total of 3372 pregnant women who attended their first prenatal
      care visit in Lima, Peru participated in the study. We assessed the reliability
      of the PCL-C items using Cronbach's alpha. Criterion validity and performance
      characteristics of PCL-C were assessed against an independent, blinded Clinician
      Administered PTSD Scale (CAPS) interview using measures of sensitivity,
      specificity and receiver operating characteristics (ROC) curves. We tested
      construct validity using exploratory and confirmatory factor analytic approaches.
      RESULTS: The reliability of the PCL-C was excellent (Cronbach's alpha =0.90). ROC
      analysis showed that a cut-off score of 26 offered optimal discriminatory power,
      with a sensitivity of 0.86 (95% CI: 0.78-0.92) and a specificity of 0.63 (95% CI:
      0.62-0.65). The area under the ROC curve was 0.75 (95% CI: 0.71-0.78). A three
      factor solution was extracted using exploratory factor analysis and was further
      complemented with three other models using confirmatory factor analysis (CFA). In
      a CFA, a three-factor model based on DSM-IV symptom structure had reasonable fit
      statistics with comparative fit index of 0.86 and root mean square error of
      approximation of 0.09. CONCLUSION: The Spanish-language version of the PCL-C may
      be used as a screening tool for pregnant women. The PCL-C has good reliability,
      criterion validity and factorial validity. The optimal cut-off score obtained by
      maximizing the sensitivity and specificity should be considered cautiously; women
      who screened positive may require further investigation to confirm PTSD
      diagnosis.

PMID- 28494806
TI  - What makes weekend allied health services effective and cost-effective (or not)
      in acute medical and surgical wards? Perceptions of medical, nursing, and allied
      health workers.
AB  - BACKGROUND: There is strong public support for acute hospital services to move to
      genuine 7-day models, including access to multidisciplinary team assessment. This
      study aimed to identify factors that might enable an effective and cost-effective
      weekend allied health services on acute hospital wards. METHODS: This qualitative
      study included 22 focus groups within acute wards with a weekend allied health
      service and 11 telephone interviews with weekend service providers. Data were
      collected from 210 hospital team members, including 17 medical, 97 nursing, and
      96 allied health professionals from two Australian tertiary public hospitals. All
      were recorded and imported into nVivo 10 for analysis. Thematic analysis methods
      were used to develop a coding framework from the data and to identify emerging
      themes. RESULTS: Key themes identified were separated into issues perceived as
      being enablers or barriers to the effective or cost-effective delivery of weekend
      allied health services. Perceived enablers of effectiveness and cost
      effectiveness included prioritizing interventions that prevent decline, the right
      person delivering the right service, improved access to the patient's family, and
      ability to impact patient flow. Perceived barriers were employment of
      inexperienced weekend staff, insufficient investment to see tangible benefit,
      inefficiencies related to double-handling, unnecessary interventions and/or
      inappropriate referrals, and difficulty recruiting and retaining skilled staff.
      CONCLUSIONS: Suggestions for ensuring effective and cost effective weekend allied
      health care models include minimization of task duplication and targeting
      interventions so that the right patients receive the right interventions at the
      right time. Further research into the effectiveness and cost effectiveness of
      these services should factor in hidden costs, including those associated with
      managing the service.

PMID- 28494805
TI  - Relative incidence and individual-level severity of seasonal influenza A H3N2
      compared with 2009 pandemic H1N1.
AB  - BACKGROUND: Two subtypes of influenza A currently circulate in humans: seasonal
      H3N2 (sH3N2, emerged in 1968) and pandemic H1N1 (pH1N1, emerged in 2009). While
      the epidemiological characteristics of the initial wave of pH1N1 have been
      studied in detail, less is known about its infection dynamics during subsequent
      waves or its severity relative to sH3N2. Even prior to 2009, few data was
      available to estimate the risk of severe outcomes following infection with one
      circulating influenza strain relative to another. METHODS: We analyzed antibodies
      in quadruples of sera from individuals in Hong Kong collected between July 2009
      and December 2011, a period that included three distinct influenza virus
      epidemics. We estimated infection incidence using these assay data and then
      estimated rates of severe outcomes per infection using population-wide clinical
      data. RESULTS: Cumulative incidence of infection was high among children in the
      first epidemic of pH1N1. There was a change towards the older age group in the
      age distribution of infections for pH1N1 from the first to the second epidemic,
      with the age distribution of the second epidemic of pH1N1 more similar to that of
      sH3N2. We found no serological evidence that individuals were infected in both
      waves of pH1N1. The risks of excess mortality conditional on infection were
      higher for sH3N2 than for pH1N1, with age-standardized risk ratios of 2.6 [95%
      CI: 1.8, 3.7] for all causes and 1.5 [95% CI: 1.0, 2.1] for respiratory causes
      throughout the study period. CONCLUSIONS: Overall increase in clinical incidence
      of pH1N1 and higher rates of severity in older adults in post pandemic waves were
      in line with an age-shift in infection towards the older age groups. The absence
      of repeated infection is good evidence that waning immunity did not cause the
      second wave. Despite circulating in humans since 1968, sH3N2 is substantially
      more severe per infection than the pH1N1 strain. Infection-based estimates of
      individual-level severity have a role in assessing emerging strains; updating
      seasonal vaccine components; and optimizing of vaccination programs.

PMID- 28494807
TI  - Concordant clear cell "mesonephric" carcinoma of the bladder and lung
      adenocarcinoma with clear cell features - multiple primaries versus metastatic
      neoplasms: a case report.
AB  - BACKGROUND: Clear cell carcinoma of the bladder is a rare variant of urinary
      bladder adenocarcinoma. We report a case of a patient with clear cell carcinoma
      of the bladder and a concordant right upper lobe pulmonary adenocarcinoma with
      clear cell features, and we address the role of immunohistochemistry and
      cytogenetic analysis in distinguishing the two primary malignancies. CASE
      PRESENTATION: Our patient was a 59-year-old African American woman who presented
      with hematuria. Her past medical history included invasive mammary carcinoma and
      end-stage renal disease treated with hemodialysis. A computed tomographic urogram
      revealed a 3-cm polypoid bladder mass. A follow-up chest computed tomographic
      scan revealed a 1-cm right upper lobe nodule. The patient underwent transurethral
      biopsy and subsequent radical cystectomy, as well as a transthoracic core needle
      biopsy of the lung nodule. Histologically, the bladder tumor consisted of flat,
      cuboidal to columnar cells with clear or eosinophilic cytoplasm and a hobnail
      appearance, organized in tubulocystic and papillary patterns. The neoplastic
      cells were diffusely positive for alpha-methylacyl-coenzyme A racemase, cancer
      antigen 125, and cytokeratin 7; focally positive for cytokeratin 20, P53, and
      carcinoembryonic antigen; and negative for thyroid transcription factor 1. The
      lung tumor demonstrated a glandular architecture with mucin production (positive
      for mucin with mucicarmine and periodic acid-Schiff with diastase stain). The
      neoplastic cells were diffusely positive for cytokeratin 7, napsin A, and thyroid
      transcription factor 1, and they were negative for cytokeratin 20 and cancer
      antigen 125. Genetic testing of the pulmonary neoplasm demonstrated ARID2 genomic
      alterations. CONCLUSIONS: The presence of clear cell features in both neoplasms
      raised the possibility of lung metastasis from the primary bladder tumor.
      However, the glandular architecture of the lung neoplasm along with its
      distinctive immunohistochemical and genetic profiles confirmed the presence of
      two separate primaries.

PMID- 28494808
TI  - Observational studies: goldmines of information on rare diseases.
AB  - The article by Savina et al. from the large METASARC database of the French
      Sarcoma Group (BMC Med 15:78, 2017) provides a wealth of information about the
      natural history and therapy of patients with metastatic soft tissue sarcomas. The
      information complements - and in some cases surpasses - that obtained from
      randomized clinical trials, and should not be overlooked because of its
      retrospective nature. For rare diseases, retrospective data are often more
      important than data from randomized trials because of the inherent restrictions
      on sample size. The article provides clear information regarding the different
      behaviors of different histological types of sarcoma, the importance of localized
      therapy for metastatic disease, and the critical role of combination chemotherapy
      in initial treatment to improve survival.Please see related article:
      https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0831-7.

PMID- 28494810
TI  - Education and equipment for people who smoke crack cocaine in Canada: progress
      and limits.
AB  - BACKGROUND: People who smoke crack cocaine experience a wide variety of health
      related issues. However, public health programming designed for this population
      is limited, particularly in comparison with programming for people who inject
      drugs. Canadian best practice recommendations encourage needle and syringe
      programs (NSPs) to provide education about safer crack cocaine smoking practices,
      distribute safer smoking equipment, and provide options for safer disposal of
      used equipment. METHODS: We conducted an online survey of NSP managers across
      Canada to estimate the proportions of NSPs that provide education and distribute
      safer smoking equipment to people who smoke crack cocaine. We also assessed
      change in pipe distribution practices between 2008 and 2015 in the province of
      Ontario. RESULTS: Analysis of data from 80 programs showed that the majority
      (0.76) provided education to clients on reducing risks associated with sharing
      crack cocaine smoking equipment and about when to replace smoking equipment
      (0.78). The majority (0.64) also distributed safer crack cocaine smoking
      equipment and over half of these programs (0.55) had done so for less than 5
      years. Among programs that distributed pipes, 0.92 distributed the recommended
      heat-resistant Pyrex and/or borosilicate glass pipes. Only 0.50 of our full
      sample reported that their program provides clients with containers for safer
      disposal of used smoking equipment. The most common reasons for not distributing
      safer smoking equipment were not enough funding (0.32) and lack of client demand
      (0.25). Ontario-specific sub-analyses showed a significant increase in the
      proportion of programs distributing pipes in Ontario from 0.15 (2008) to 0.71
      (2015). CONCLUSIONS: Our findings point to important efforts by Canadian NSPs to
      reduce harm among people who smoke crack cocaine through provision of education
      and equipment, but there are still limits that could be addressed. Our study can
      provide guidance for future cross-jurisdiction studies to describe relationships
      involving harm reduction programs and provision of safer crack cocaine smoking
      education and equipment.

PMID- 28494809
TI  - The PED-t trial protocol: The effect of physical exercise -and dietary therapy
      compared with cognitive behavior therapy in treatment of bulimia nervosa and
      binge eating disorder.
AB  - BACKGROUND: Sufferers from bulimia nervosa (BN) and binge eating disorder (BED)
      underestimate the severity risk of their illness and, therefore, postpone seeking
      professional help for years. Moreover, less than one in five actually seek
      professional help and only 50% respond to current treatments, such as cognitive
      behavioral therapy (CBT). The impetus for the present trial is to explore a novel
      combination treatment approach adapted from physical exercise- and dietary
      therapy (PED-t). The therapeutic underpinnings of these separate treatment
      components are well-known, but their combination to treat BN and BED have never
      been previously tested. The purpose of this paper is to provide the rationale for
      this new treatment approach and to outline the specific methods and procedures.
      METHODS: The PED-t trial uses a prospective randomized controlled design. It
      allocates women between 18 and 40 years (BMI range 17.5-35.0) to groups
      consisting of 5-8 members who receive either CBT or PED-t for 16 weeks. Excess
      participants are allocated to a waiting list control group condition. All
      participants are assessed at baseline, post-treatment, 6, 12 and 24 months' post
      follow-up, respectively, and monitored for changes in biological, psychological
      and therapy process variables. The primary outcome relates to the ED symptom
      severity, while secondary outcomes relates to treatment effects on physical
      health, treatment satisfaction, therapeutic alliance, and cost-effectiveness. We
      aim to disseminate the results in high-impact journals, preferable open access,
      and at international conferences. DISCUSSION: We expect that the new treatment
      will perform equal to CBT in terms of behavioral and psychological symptoms, but
      better in terms of reducing somatic symptoms and complications. We also expect
      that the new treatment will improve physical fitness and thereby, quality of
      life. Hence, the new treatment will add to the portfolio of evidence-based
      therapies and thereby provide a good treatment alternative for females with BN
      and BED. TRIAL REGISTRATION: Prospectively registered in REC the 16th of December
      2013 with the identifier number 2013/1871 , and in Clinical Trials the 17th of
      February 2014 with the identifier number NCT02079935 .

PMID- 28494811
TI  - The association between implementation strategy use and the uptake of hepatitis C
      treatment in a national sample.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a common and highly morbid illness. New
      medications that have much higher cure rates have become the new evidence-based
      practice in the field. Understanding the implementation of these new medications
      nationally provides an opportunity to advance the understanding of the role of
      implementation strategies in clinical outcomes on a large scale. The Expert
      Recommendations for Implementing Change (ERIC) study defined discrete
      implementation strategies and clustered these strategies into groups. The present
      evaluation assessed the use of these strategies and clusters in the context of
      HCV treatment across the US Department of Veterans Affairs (VA), Veterans Health
      Administration, the largest provider of HCV care nationally. METHODS: A 73-item
      survey was developed and sent to all VA sites treating HCV via electronic survey,
      to assess whether or not a site used each ERIC-defined implementation strategy
      related to employing the new HCV medication in 2014. VA national data regarding
      the number of Veterans starting on the new HCV medications at each site were
      collected. The associations between treatment starts and number and type of
      implementation strategies were assessed. RESULTS: A total of 80 (62%) sites
      responded. Respondents endorsed an average of 25 +/- 14 strategies. The number of
      treatment starts was positively correlated with the total number of strategies
      endorsed (r = 0.43, p < 0.001). Quartile of treatment starts was significantly
      associated with the number of strategies endorsed (p < 0.01), with the top
      quartile endorsing a median of 33 strategies, compared to 15 strategies in the
      lowest quartile. There were significant differences in the types of strategies
      endorsed by sites in the highest and lowest quartiles of treatment starts. Four
      of the 10 top strategies for sites in the top quartile had significant
      correlations with treatment starts compared to only 1 of the 10 top strategies in
      the bottom quartile sites. Overall, only 3 of the top 15 most frequently used
      strategies were associated with treatment. CONCLUSIONS: These results suggest
      that sites that used a greater number of implementation strategies were able to
      deliver more evidence-based treatment in HCV. The current assessment also
      demonstrates the feasibility of electronic self-reporting to evaluate ERIC
      strategies on a large scale. These results provide initial evidence for the
      clinical relevance of the ERIC strategies in a real-world implementation setting
      on a large scale. This is an initial step in identifying which strategies are
      associated with the uptake of evidence-based practices in nationwide healthcare
      systems.

PMID- 28494812
TI  - Whole blood gene expression in adolescent chronic fatigue syndrome: an
      exploratory cross-sectional study suggesting altered B cell differentiation and
      survival.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition
      affecting adolescents. The pathophysiology is poorly understood, but immune
      alterations might be an important component. This study compared whole blood gene
      expression in adolescent CFS patients and healthy controls, and explored
      associations between gene expression and neuroendocrine markers, immune markers
      and clinical markers within the CFS group. METHODS: CFS patients (12-18 years
      old) were recruited nation-wide to a single referral center as part of the
      NorCAPITAL project. A broad case definition of CFS was applied, requiring 3
      months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas
      no accompanying symptoms were necessary. Healthy controls having comparable
      distribution of gender and age were recruited from local schools. Whole blood
      samples were subjected to RNA sequencing. Immune markers were blood leukocyte
      counts, plasma cytokines, serum C-reactive protein and immunoglobulins.
      Neuroendocrine markers encompassed plasma and urine levels of catecholamines and
      cortisol, as well as heart rate variability indices. Clinical markers consisted
      of questionnaire scores for symptoms of post-exertional malaise, inflammation,
      fatigue, depression and trait anxiety, as well as activity recordings. RESULTS: A
      total of 29 CFS patients and 18 healthy controls were included. We identified 176
      genes as differentially expressed in patients compared to controls, adjusting for
      age and gender factors. Gene set enrichment analyses suggested impairment of B
      cell differentiation and survival, as well as enhancement of innate antiviral
      responses and inflammation in the CFS group. A pattern of co-expression could be
      identified, and this pattern, as well as single gene transcripts, was
      significantly associated with indices of autonomic nervous activity, plasma
      cortisol, and blood monocyte and eosinophil counts. Also, an association with
      symptoms of post-exertional malaise was demonstrated. CONCLUSION: Adolescent CFS
      is characterized by differential gene expression pattern in whole blood
      suggestive of impaired B cell differentiation and survival, and enhanced innate
      antiviral responses and inflammation. This expression pattern is associated with
      neuroendocrine markers of altered HPA axis and autonomic nervous activity, and
      with symptoms of post-exertional malaise. Trial registration Clinical Trials
      NCT01040429.

PMID- 28494814
TI  - Erratum to: Analysis of necroptotic proteins in failing human hearts.

PMID- 28494815
TI  - Association between fluid intake and mortality in critically ill patients with
      negative fluid balance: a retrospective cohort study.
AB  - BACKGROUND: Compared to positive fluid balance (FB), negative FB is associated
      with improved clinical outcomes in critically ill patients. However, as to
      whether achieving more negative FB can further improve outcomes has not been
      investigated. This study aimed to investigate whether more negative FB and
      restricted fluid intake were associated with improved outcomes in critically ill
      patients. METHOD: Data were extracted from the Multi-parameter Intelligent
      Monitoring in Intensive Care III Database. Patients achieving negative FB at 48
      hours after intensive care unit (ICU) admission were screened. The primary
      outcome was hospital mortality. Logistic models were built to explore the
      association between FB, fluid intake and mortality, using FB and fluid intake
      (both four levels) as design variables and using the linear spline function
      method. RESULTS: There were 2068 patients meeting the inclusion criteria.
      Compared to slight negative FB (level 1), there was a decreased tendency towards
      mortality with FB level 2 (OR 0.88, 95% CI 0.69-1.11) and level 3 (OR 0.79, 95%
      CI 0. 65-1.11); however, only extreme negative FB (level 4) was significant (OR
      0.56, 95% CI 0. 33-0.95). Fluid intake and urine output were evenly distributed
      over the first 48 hours after ICU admission. Fluid intake was inversely
      associated with hospital mortality, with the OR decreased stepwise from level 2
      (OR 0.73, 95% CI 0.56-0.96) to level 4 (OR 0.47, 95% CI 0.30-0.74), referred to
      level 1. Urine output also showed a similar pattern. Diuretic use was associated
      with higher mortality in both models. CONCLUSION: In critically ill patients with
      negative FB, both increased fluid intake and urine output were associated with
      decreased hospital mortality. However, compared to slight FB, achieving more
      negative FB was not associated with reduced mortality.

PMID- 28494813
TI  - Not only dominant, not only optic atrophy: expanding the clinical spectrum
      associated with OPA1 mutations.
AB  - BACKGROUND: Heterozygous mutations in OPA1 are a common cause of autosomal
      dominant optic atrophy, sometimes associated with extra-ocular manifestations.
      Few cases harboring compound heterozygous OPA1 mutations have been described
      manifesting complex neurodegenerative disorders in addition to optic atrophy.
      RESULTS: We report here three patients: one boy showing an early-onset
      mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely
      progressive, leading to early death because of multiorgan failure; two unrelated
      sporadic girls manifesting a spastic ataxic syndrome associated with peripheral
      neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132
      genes associated with mitochondrial disorders, in two probands we found compound
      heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a
      frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a
      missense change (p.Ile437Met), which has recently been reported to have clinical
      impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the
      p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A
      (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing
      approach. One of the patients presented also variants in mitochondrial DNA that
      may have contributed to the peculiar phenotype. The deleterious effect of the
      identified missense changes was experimentally validated in yeast model. OPA1
      level was reduced in available patients' biological samples, and a clearly
      fragmented mitochondrial network was observed in patients' fibroblasts.
      CONCLUSIONS: This report provides evidence that bi-allelic OPA1 mutations may
      lead to complex and severe multi-system recessive mitochondrial disorders, where
      optic atrophy might not represent the main feature.

PMID- 28494816
TI  - A giant squamous cell carcinoma of the skin of the thoracic wall: a case report
      and review of the literature.
AB  - BACKGROUND: We report a case of a 48-year-old white woman who presented with a
      huge cutaneous protruding tumor of the thoracic wall below her left breast. CASE
      PRESENTATION: The lesion was excised with clear margins from the adjacent skin,
      and subcutaneous tissue was left to heal with second intention. A histological
      examination of the surgical specimen revealed a well-differentiated infiltrative
      cutaneous squamous cell carcinoma. Our patient neglected to attend our
      Oncological Department to receive chemotherapy. Today, 12 months after surgery,
      she is alive and without evidence of disease recurrence. CONCLUSIONS: Cutaneous
      squamous cell carcinoma can reach a huge size if left untreated. Surgery is the
      primary mode of treatment, followed by chemotherapy if applicable.

PMID- 28494817
TI  - Comparison of cognitive functioning as measured by the Ruff Figural Fluency Test
      and the CogState computerized battery within the LifeLines Cohort Study.
AB  - BACKGROUND: The Ruff Figural Fluency Test (RFFT; a pencil and paper test) and the
      CogState (a computerized cognitive test battery) are well-validated and suitable
      tests to evaluate cognitive functioning in large observational studies at the
      population level. The LifeLines Cohort Study includes the RFFT as baseline
      measurement and incorporated the CogState as replacement for the RFFT at follow
      up. It is unknown how these two tests relate to each other. Therefore, the aim of
      this study is to examine the correlation between the RFFT and the CogState and
      the impact of demographic characteristics on this association. METHODS: A
      subcohort of the LifeLines Cohort Study, a large population based cohort study,
      participated in this study. Correlations between the RFFT and six subtasks of the
      CogState were examined. Subgroup analyses were performed to investigate the
      influence of age, education, and gender on the results. With sensitivity analyses
      we investigated the influence of computer experience and (physical) impairments.
      RESULTS: A total of 509 participants (mean age (SD): 53 years (14.6); range 18-87
      years) participated in this study. All correlations between the RFFT and the
      CogState were statistically significant (except for the correlation between the
      RFFT error ratio and the CogState One Back Task), ranging from -0.39 to 0.28.
      Stratifying the analyses for age, education, and gender did not substantially
      affect our conclusions. Sensitivity analyses showed no substantial influence of
      level of computer experience or (physical) impairments. CONCLUSIONS: Correlations
      found in the present study were only weak to moderate, indicating that cognitive
      functioning measured by the RFFT does not measure the same components of
      cognitive functioning as six subtasks of the CogState. Computerized testing such
      as the CogState may be very well suited for large cohort studies to assess
      cognitive functioning in the general population and to identify cognitive changes
      as early as possible, as it is a less time- and labor intensive tool.

PMID- 28494818
TI  - Is there echinococcosis in West Africa? A refugee from Niger with a liver cyst.
AB  - BACKGROUND: Italy is presently facing an increase in immigration from sub-Saharan
      Africa through the Mediterranean Sea. Case reports of human cystic echinococcosis
      (CE) have been reported from most sub-Saharan countries. Therefore, an increase
      in the number of patients with CE coming from these areas in the Italian and
      European centers for infectious diseases is expected. Unfortunately, the
      epidemiology of CE in sub-Saharan countries is poorly known, which makes clinical
      suspicion and diagnosis of such infection difficult in patients coming from these
      areas. RESULTS: Here we report a case of hepatic CE in a patient from Niger who
      arrived in Italy through Libya and visited in a Tropical Medicine referral center
      in Northern Italy. The parasite was identified molecularly as the G6 "camel"
      strain of Echinococcus granulosus (E. canadensis). The diagnosis and management
      of a chronic and clinically complex infection like CE in such situation is
      difficult. Only 40 cases of CE from Niger have been reported; of these, 75% had
      extra-hepatic localization. To our knowledge, no strain characterization of human
      isolates from Niger has been reported so far. The CE cyst of the patient was in
      CE3a stage, indicating active transmission from the area in which the patient
      came. However, prevalence data from Niger, and from any other country in West
      Africa, are almost inexistent. CONCLUSIONS: We argue that population epidemiology
      surveys with ultrasound are warranted in Sahelian countries, including Niger.
      These studies could improve the knowledge of CE epidemiology, provide health
      authorities with important information for public health interventions targeting
      this zoonosis, and shed light on any difference between tissue tropism and
      clinical manifestations caused by the different E. granulosus strains.

PMID- 28494819
TI  - Mild Cognitive Impairment in Parkinson's Disease: Clustering and Switching
      Analyses in Verbal Fluency Test.
AB  - OBJECTIVES: Mild cognitive impairment is common in non-demented Parkinson disease
      patients (PD-MCI) and is considered as a risk factor for dementia. Executive
      dysfunction has been widely described in PD and the Verbal Fluency Tests (VFT)
      are often used for executive function assessment in this pathology. The Movement
      Disorder Society (MDS) published guidelines for PD-MCI diagnosis in 2012.
      However, no investigation has focused on the qualitative analysis of VFT in PD
      MCI. The aim of this work was to study the clustering and switching strategies in
      VFT in PD-MCI patients. Moreover, these variables are considered as predictors
      for PD-MCI diagnosis. METHODS: Forty-three PD patients and twenty normal controls
      were evaluated with a neuropsychological protocol and the MDS criteria for PD-MCI
      were applied. Clustering and switching analysis were conducted for VFT. RESULTS:
      The percentage of patients diagnosed with PD-MCI was 37.2%. The Mann-Whitney U
      test analysis showed that PD-MCI performed poorly in different cognitive measures
      (digit span, Wisconsin Card Sorting Test, judgment of line orientation, and
      comprehension test), compared to PD patients without mild cognitive impairment
      (PD-nMCI). Phonemic fluency analyses showed that PD-MCI patients produced fewer
      words and switched significantly less, compared to controls and PD-nMCI.
      Concerning semantic fluency, the PD-MCI group differed significantly, compared to
      controls and PD-nMCI, in switches. Discriminant function analyses and logistic
      regression analyses revealed that switches predicted PD-MCI. CONCLUSIONS: PD-MCI
      patients showed poor performance in VFT related to the deficient use of
      production strategies. The number of switches is a useful predictor for incident
      PD-MCI. (JINS, 2017, 23, 511-520).

PMID- 28494820
TI  - Positive and Negative Consequences of Making Coffee among Breakfast Related
      Irrelevant Objects: Evidence from MCI, Dementia, and Healthy Ageing.
AB  - OBJECTIVES: Previous studies have reported impairments in activities of daily
      living (ADL) performance in the presence of irrelevant but
      physically/functionally related objects in dementia patients. The aim of the
      present study was to increase our knowledge about the impact of the presence of
      contextually related non-target objects on ADL execution in patients with multi
      domain mild cognitive impairment (MCI) and dementia. METHODS: We compared ADL
      execution in patients with MCI, dementia, and healthy elderly participants under
      two experimental conditions: One in which the target objects were embedded with
      contextually related non-target items that constituted the object set necessary
      to complete two additional (but unrequired) ADL tasks related to the target task,
      and a second, control condition where target objects were surrounded by isolated
      objects (they never constituted a whole set needed to complete an alternative ADL
      task). RESULTS: Separate analysis of ADL errors associated with the target task
      versus errors involving the non-target objects revealed that, although the
      presence of contextually related objects facilitated the accomplishment of the
      target task, such a condition also led to errors involving the use of irrelevant
      objects in dementia and MCI. CONCLUSIONS: The presence of contextually related
      non-target items produces both positive and negative effects on ADL performance.
      These types of non-target objects might help to cue the retrieval of the action
      schema related to the target task, particularly in patients with MCI. In
      contrast, the presence of these objects might also lead to distraction in
      dementia and MCI. (JINS, 2017, 23, 481-492).

PMID- 28494821
TI  - Abstracts for the 24th Annual Meeting of the American Society for Neural Therapy
      and Repair.

PMID- 28494822
TI  - Nursing: The Balance of Mind, Body, and Spirit.

PMID- 28494823
TI  - An Introduction to Epigenetics.
AB  - Epigenetics refers to the heritable information that is exclusive of DNA. Several
      syndromes have been found to occur as the result of the process of epigenetics.
      This process causes changes in the expression of genes, without changing the
      actual DNA sequence. The factors influencing this process include both internal
      and external triggers, leading to modulation of the epigenome through different
      mechanisms. This article aims to describe how the process of epigenetics gives
      rise to the multitude of possible syndromes seen in neonates. The article will
      also discuss the role of assisted reproductive technology may play in epigenetic
      changes when compared with the naturally conceived embryo.

PMID- 28494824
TI  - Beckwith-Wiedemann Syndrome Review: A Guide for the Neonatal Nurse.
AB  - Beckwith-Wiedemann syndrome (BWS) is the most common pediatric overgrowth
      syndrome. Features characteristic of the BWS phenotype include both physical
      attributes, such as macroglossia, abdominal wall defects, gigantism, nevus
      flammeus, visceromegaly, and mid-face hypoplasia, as well as biochemical
      abnormalities such as hypoglycemia. It is essential for the neonatal nurse to be
      able to recognize BWS in the patient's early years of life because of the
      increased frequency of medical complications, malformations, and the increased
      risk of embryonic malignancies. This article focuses on the presentation of BWS
      as an aid to early detection.

PMID- 28494825
TI  - Prader-Willi Syndrome: Background and Management.
AB  - The imprinting disorder, Prader-Willi syndrome, is a condition associated with
      the gene region 15q11.2-q.13. The phenotype includes multiple characteristics,
      most of which are endocrine-related. An accurate diagnosis is done mostly through
      pre- or postnatal genetic testing. Management is mainly aimed at correcting the
      endocrine dysfunctions present in these patients. Genetic testing is also
      important to distinguish between the different causes and to calculate the
      recurrence risk for parents with affected children. Although a lot has been
      discovered and this syndrome can be managed to a satisfactory degree, further
      research is still important especially regarding new potential treatments with
      greater efficiency and reduced invasiveness. The neonatal nurse has an important
      role because the management requires thorough monitoring as well as high
      compliance from both the patient and the carers. Thus, it is essential for the
      neonatal nurse to have a good knowledge of this condition.

PMID- 28494826
TI  - Angelman Syndrome: Identification and Management.
AB  - Angelman syndrome (AS) is a neurobehavioral and genetically determined condition,
      which affects approximately 1 in 15,000 individuals. It is caused by various
      genetic mutations and deletions of the maternally-inherited UBE3A gene, on the
      15q11-13 chromosomal region. The UBE3A gene, which encodes E3 ubiquitin ligase,
      shows tissue-specific imprinting, being expressed entirely from the maternal
      allele.The diagnosis of AS is confirmed either by methylation test or by mutation
      analysis. A more severe clinical picture is linked with the deletion
      phenotype.Patients with AS have a behavioral and motor pattern defined as "happy
      puppet" because it is characterized by puppet-like ataxic jerky movements; a
      happy, sociable disposition; and paroxysms of laughter. There is currently no
      cure for AS, and management is mainly symptomatic. Novel therapeutic options are
      directed toward the possibility of activating the silenced paternal copy of the
      UBE3A gene.

PMID- 28494827
TI  - Use of Placental/Umbilical Blood Sampling for Neonatal Admission Blood Cultures:
      Benefits, Challenges, and Strategies for Implementation.
AB  - Placental blood remains an underused resource for early neonatal care despite
      ample evidence that placental blood provides the same clinical decision making
      information without the need for painful, invasive blood sampling procedures.
      Potential benefits of placental/umbilical blood sampling (PUBS) for neonatal
      admission labs include decreases in pain reactivity, rates of anemia, need for
      blood transfusions, use of vasopressors, and rates of intraventricular
      hemorrhage. Here, we present a unique case study of a critically ill infant with
      contradictory blood culture results from PUBS and direct infant sampling. A
      negative admission direct sample blood culture result compared with a positive
      admission PUBS blood culture result suggests that infection may have been missed
      in the direct infant sample. Relevant placental embryology and circulation is
      also described, as well as the benefits of PUBS for neonatal admission labs (with
      focus on the blood culture), challenges associated with PUBS practice, and
      strategies for implementation of PUBS.

PMID- 28494829
TI  - Faith's Lodge: A Place of Peace for NICU Families in Grief or in Complex Health
      Situations.
AB  - Parents confronting the death of a child or working through the complex health
      needs of a child often feel isolated in their communities. They seek a personal
      connection with others who are going through similar emotions. Faith's Lodge is a
      unique respite for those families to find a place to reflect, find peace, and
      more.

PMID- 28494830
TI  - Continuing Education Course.

PMID- 28494828
TI  - Treatment of Persistent Pulmonary Hypertension of the Newborn: Use of Pulmonary
      Vasodilators in Term Neonates.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) represents a challenging
      condition associated with significant morbidity. A successful transition from
      intrauterine to extrauterine life is contingent on adequate pulmonary
      vasodilation. Several pathophysiologies contribute to the failure of this cascade
      and may result in life-threatening hypoxia and acidosis in the newborn.
      Management includes optimal respiratory support, adequate sedation and analgesia,
      and support of vascular tone and cardiac function. Pulmonary vasodilation has the
      potential to overcome the cycle of hypoxia and acidosis, improving outcome in
      these infants. Oxygen and inhaled nitric oxide represent the foundation of
      therapy. Tertiary pulmonary vasodilators represent a greater challenge, selecting
      between therapies that include prostanoids, sildenafil, and milrinone. Variable
      levels of evidence exist for each agent. Thorough review of available data
      informing efficacy and adverse effects contributes to the development of an
      informed approach to neonates with refractory PPHN.

PMID- 28494831
TI  - News of the Academy of Neonatal Nursing.

PMID- 28494834
TI  - Prediction of 10-year Atherosclerotic Cardiovascular Disease Risk among Adults
      Aged 40-79 Years in China: a Nationally Representative Survey.
AB  - OBJECTIVE: To establish the distribution of 10-year atherosclerotic
      cardiovascular disease (ASCVD) risk among Chinese adults. METHODS: We estimated
      the 10-year ASCVD risk by applying the 2013 American College of Cardiology/
      American Heart Association pooled cohort equations (PCEs) to the data obtained
      from the 2010 China Chronic Disease and Risk Factor Surveillance that involved
      61,541 participants (representing 520,158,652 Chinese adults) aged 40-79 years.
      We also compared the ASCVD risk with the 10-year ischemic cardiovascular disease
      (ICVD) risk, which was calculated using the simplified scoring tables recommended
      by the Chinese Guidelines for Prevention of Cardiovascular Diseases (Chinese
      model). RESULTS: Based on the PCEs, the average 10-year ASCVD risk among adults
      without self-reported stroke or myocardial infraction was 12.5%. Approximately
      247 million (47.4%) and 107 million (20.6%) adults had ? 7.5% and > 20% 10-year
      ASCVD risks, respectively. The 10-year ASCVD risk > 20% was higher among men,
      less educated individuals, smokers, drinkers, and physically inactive individuals
      than among their counterparts. Overall, 29.0% of adults categorized using the
      Chinese model were overclassified with the PCEs. CONCLUSION: Our results define
      the distribution of 10-year ASCVD risk among Chinese adults. The 10-year ASCVD
      risk predicted by the PCEs was higher than the ICVD risk predicted by the Chinese
      model.

PMID- 28494833
TI  - Impact of Smoking Status on Lipoprotein Subfractions: Data from an Untreated
      Chinese Cohort.
AB  - OBJECTIVE: Cigarette smoking is one of the established risk factors of
      atherosclerotic cardiovascular disease, however, its impact on lipids is not
      completely understood, especially in the Chinese population. Therefore, this
      study evaluated the impact of smoking status (non, former, and current smoking)
      on the distribution of lipoprotein subfractions in untreated patients with angina
      like chest pain. METHODS: A total of 877 patients were consecutively enrolled and
      divided into nonsmoking (n = 518), former smoking (n = 103), and current smoking
      (n = 256) groups. Both low- and high-density lipoprotein cholesterol (LDL-C and
      HDL-C) subfractions were measured using the Quantimetrix Lipoprint System. The
      distributions of lipoprotein subfractions were evaluated among the groups.
      RESULTS: Compared with nonsmoking subjects, the current smoking group had
      significantly lower large/medium HDL-C (both P < 0.001) concentration and large
      HDL subfraction percentage but higher small HDL-C and medium LDL-C concentrations
      as well as medium LDL subfraction percentage. Importantly, former smoking
      subjects showed elevated levels of large HDL-C concentration, large HDL particle
      percentage, and mean LDL particle size and attenuation in small HDL/LDL
      percentages and small LDL-C concentration, but these levels did not reach the
      optimal status compared with those of the non-smoking group (data not shown).
      CONCLUSION: Smoking has an adverse impact on the lipoprotein subfractions,
      presented as lower large HDL particles besides higher small HDL and medium LDL
      particles, whereas smoking cessation could reverse these change to a certain
      degree.

PMID- 28494835
TI  - Validation of the Simplified Chinese-character Version of the International
      Physical Activity Questionnaire-Long Form in Urban Community-dwelling Adults: a
      Cross-sectional Study in Hangzhou, China.
AB  - OBJECTIVE: To assess the test-retest reliability and criterion validity of the
      Simplified Chinese-character version of the International Physical Activity
      Questionnaire Long form (IPAQ-L) in urban community-dwelling adults in Hanghzou,
      China. METHODS: A total of 158 eligible participants aged 25-59 years from 6
      neighbourhoods in two central districts of Hangzhou completed the IPAQ-L
      questionnaire twice within a 7-day interval. Half of the subjects wore pedometers
      during the first 7 days. Test-retest reliability was examined by comparing the
      first (Day 1) and the second (Day 9) survey of IPAQ-L. Criterion validity was
      assessed by comparing IPAQ-L with pedometer data. RESULTS: Modest to good test
      retest reliability was found with intraclass correlation coefficients of 0.67 for
      total PA, 0.37 to 0.73 for specific dimensions, and 0.56 to 0.71 for different
      intensities of PA. Total PA measured by IPAQ-L was moderately correlated with
      exercise levels (partial r = 0.27, P = 0.020) and walking distance (partial r =
      0.31, P = 0.007), which were measured by a pedometer, after adjusting for gender,
      age, educational attainment and employment status. CONCLUSION: Our results
      indicate that the IPAQ-L is a reliable and validated measure for assessing
      physical activity levels in this population and possibly the adult population in
      other mainland Chinese cities.

PMID- 28494836
TI  - Pulmonary Toxicity in Rats Caused by Exposure to Intratracheal Instillation of
      SiO2 Nanoparticles.
AB  - OBJECTIVE: The effect of the silica nanoparticles (SNs) on lungs injury in rats
      was investigated to evaluate the toxicity and possible mechanisms for SNs.
      METHODS: Male Wistar rats were instilled intratracheally with 1 mL of saline
      containing 6.25, 12.5, and 25.0 mg of SNs or 25.0 mg of microscale SiO2 particles
      suspensions for 30 d, were then sacrificed. Histopathological and ultrastructural
      change in lungs, and chemical components in the urine excretions were
      investigated by light microscope, TEM and EDS. MDA, NO and hydroxyproline (Hyp)
      in lung homogenates were quantified by spectrophotometry. Contents of TNF-alpha,
      TGF-beta1, IL-1beta, and MMP-2 in lung tissue were determined by
      immunohistochemistry staining. RESULTS: There is massive excretion of Si
      substance in urine. The SNs lead pulmonary lesions of rise in lung/body
      coefficients, lung inflammation, damaged alveoli, granuloma nodules formation,
      and collagen metabolized perturbation, and lung tissue damage is milder than
      those of microscale SiO2 particles. The SNs also cause increase lipid
      peroxidation and high expression of cytokines. CONCLUSION: The SNs result into
      pulmonary fibrosis by means of increase lipid peroxidation and high expression of
      cytokines. Milder effect of the SNs on pulmonary fibrosis comparing to microscale
      SiO2 particles is contributed to its elimination from urine due to their
      ultrafine particle size.

PMID- 28494837
TI  - The Association between the C5263T Mutation in the Mitochondrial ND2 Gene and
      Coronary Heart Disease among Young Chinese Han People.
AB  - OBJECTIVE: This study aimed to investigate the genetic background of
      mitochondrial genes in young patients with Coronary heart disease (CHD) to
      provide a foundation for the early prevention of young patients with CHD.
      METHODS: 115 cases of young (? 45 years) CHD Chinese Han patients (case group),
      100 cases of older (> 45 years) Chinese Han CHD patients (experimental group)
      hospitalized and 100 cases of healthy people through physical examination
      (control group) at the General Hospital of PLA between January 2014 and December
      2015 were selected. General information, clinical assessment, pedigree analysis,
      and mitochondrial full sequence scanning were performed. The pedigrees of one
      patient harbouring the C5263T mutation were recruited. Mitochondrial functional
      analysis including cellular reactive oxygen species (ROS) levels and
      mitochondrial membrane potential (MMP) were performed on pedigrees with the
      C5263T mutation (mutation group) and without the mutation (non-mutation group).
      RESULTS: The differences in biochemical tests (P > 0.05) between the case group
      and experimental group were not significant. The C5263T single-nucleotide
      mutation of the mitochondrial ND2 gene was observed in 2 young CHD patients in
      the case group. The premature CHD of these 2 patients followed a pattern of
      maternal inheritance. The mutation group (I1, II2) had higher ROS levels (4750.82
      +/- 1045.55 vs. 3888.58 +/- 487.60, P = 0.022) and lower MMP levels (P = 0.045)
      than the non-mutation group (II1, III1, III2). CONCLUSION: We speculated that the
      mitochondrial C5263T mutation might be associated with the occurrence CHD in
      Chinese Han young people.

PMID- 28494838
TI  - Association between the SUMO4 M55V Polymorphism and Susceptibility to Type 2
      Diabetes Mellitus: A Meta-analysis.
AB  - OBJECTIVE: The aim of this study is to determine whether the SUMO4 M55V
      polymorphism is associated with susceptibility to type 2 diabetes mellitus
      (T2DM). METHODS: A meta-analysis was performed to detect the potential
      association of the SUMO4 M55V polymorphism and susceptibility to T2DM under
      dominant, recessive, co-dominant (homogeneous and heterogeneous), and additive
      models. RESULTS: A total of eight articles including 10 case-control studies,
      with a total of 2932 cases and 2679 controls, were included in this meta
      analysis. The significant association between the SUMO4 M55V polymorphism and
      susceptibility to T2DM was observed in the dominant model (GG + GA versus AA: OR
      = 1.21, 95% CI = 1.05-1.40, P = 0.009), recessive model (GG versus GA + AA: OR =
      1.29, 95% CI = 1.07-1.356, P = 0.010), homozygous model (GG versus AA: OR = 1.41,
      95% CI = 1.06-1.56, P = 0.001), and additive model (G versus A: OR = 1.18, 95% CI
      = 1.08-1.29, P = 0.001), and marginally significant in the heterozygous model (GA
      versus AA: OR = 1.16, 95% CI = 0.98-1.36, P = 0.080). In subgroup analyses,
      significant associations were observed in the Chinese population under four
      genetic models excluding the heterozygous model, whereas no statistically
      significant associations were observed in the Japanese population under each of
      the five genetic models. CONCLUSION: The meta-analysis demonstrated that the G
      allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to T2DM,
      mainly in the Chinese population, while the association in other ethnic
      population needs to be further validated in studies with relatively large
      samples.

PMID- 28494839
TI  - Hexabromocyclododecane-induced Genotoxicity in Cultured Human Breast Cells
      through DNA Damage.
AB  - To investigate the genotoxicity and reveal the potential toxicological mechanisms
      of Hexabromocyclododecane (HBCD), human breast cells HBL-100 were exposed to a
      sequence of HBCD concentrations (0, 5, 10, and 50 mg/L) for 24 h. With a series
      of zymology and molecular biology methods, we found that HBCD induced dose
      dependent oxidative stress on HBL-100 DNA. As revealed in qRT-PCR, activated
      prognostic factor ATM down-regulated tumor suppressor gene BRCA1 and prompted DNA
      repair genes hOGG1 and hMTH1 expression in lower concentrations of HBCD (< 10
      mg/L). However, DNA repair were inhibited as well as cell proliferation rate by
      higher concentrations of HBCD (50 mg/L). The results inferred that the
      genotoxicity of HBCD was dose-dependent and related to DNA repair pathway.

PMID- 28494840
TI  - Differential Proteomics Reveals the Potential Injury Mechanism Induced by Heavy
      Ion Radiation in Mice Ovaries.
AB  - In the present study, we used a proteomics approach based on a two-dimensional
      electrophoresis (2-DE) reference map to investigate protein expression in the
      ovarian tissues of pubertal Swiss-Webster mice subjected to carbon ion radiation
      (CIR). Among the identified proteins, ubiquitin carboxy-terminal hydrolase L1
      (UCH-L1) is associated with the cell cycle[1] and that it influences
      proliferation in ovarian tissues. We analyzed the expression of UCH-L1 and the
      proliferation marker proliferation cell nuclear antigen (PCNA) following CIR
      using immunoblotting and immunofluorescence. The proteomics and biochemical
      results provide insight into the underlying mechanisms of CIR toxicity in ovarian
      tissues.

PMID- 28494841
TI  - Quercetin Attenuates Benzo(alpha)pyrene-induced CYP1A Expression.
AB  - We studied effects of nutrient quercetin on cytochromes' R450 1A (CYP1A)
      activities (measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1
      and 7-methoxy-resorufin for CYP1A2 as substrates), on mRNA levels (measured by RT
      PCR), and on DNA-binding activities (evaluated by an electrophoretic mobility
      shift assay) of proteins regulating CYP1A expression in untreated and
      benzo(alpha)pyrene (BaP)-treated rats. Wistar rats received quercetin, BaP, or
      both once daily for 1-3 days. Quercetin did not influence CYP1A1 in untreated
      rats but inhibited BaP-mediated CYP1A induction on the transcriptional level
      decreasing positive input (AhR functional activity) and increasing negative input
      (AhRR/ARNT expression and Oct-1 and C/EBP functional activities).

PMID- 28494842
TI  - Two consecutive large outbreaks of Salmonella Muenchen linked to pig farming in
      Germany, 2013 to 2014: Is something missing in our regulatory framework?
AB  - In 2013, raw pork was the suspected vehicle of a large outbreak (n = 203 cases)
      of Salmonella Muenchen in the German federal state of Saxony. In 2014, we
      investigated an outbreak (n = 247 cases) caused by the same serovar affecting
      Saxony and three further federal states in the eastern part of Germany. Evidence
      from epidemiological, microbiological and trace-back investigations strongly
      implicated different raw pork products as outbreak vehicles. Trace-back analysis
      of S. Muenchen-contaminated raw pork sausages narrowed the possible source down
      to 54 pig farms, and S. Muenchen was detected in three of them, which traded
      animals with each other. One of these farms had already been the suspected source
      of the 2013 outbreak. S. Muenchen isolates from stool of patients in 2013 and
      2014 as well as from food and environmental surface swabs of the three pig farms
      shared indistinguishable pulsed-field gel electrophoresis patterns. Our results
      indicate a common source of both outbreaks in the primary production of pigs.
      Current European regulations do not make provisions for Salmonella control
      measures on pig farms that have been involved in human disease outbreaks. In
      order to prevent future outbreaks, legislators should consider tightening
      regulations for Salmonella control in causative primary production settings.

PMID- 28494843
TI  - Passive enhanced safety surveillance for Vaxigrip and Intanza 15 ug in the United
      Kingdom and Finland during the northern hemisphere influenza season 2015/16.
AB  - Enhanced safety surveillance (ESS) was conducted in the United Kingdom and
      Finland for Vaxigrip and Intanza 15 ug to comply with the European Medicines
      Agency interim guidance aimed to detect any potential increase in reactogenicity
      in near real time following the annual update of the influenza vaccine strain
      composition. This pilot passive ESS was established to strengthen safety
      monitoring by facilitating spontaneous vaccinee reports and estimating near real
      time vaccinee exposure. The primary objective was to estimate the reporting rates
      of suspected adverse reactions (ARs) occurring within 7 days post vaccination
      during the northern hemisphere 2015/16 influenza season. Among the Vaxigrip
      vaccinees (n = 1,012), 32 (3.2%) reported a total of 122 suspected ARs, including
      110 suspected ARs that occurred within 7 days post vaccination. Among the Intanza
      15 ug vaccinees (n = 1,017), 31 (3.0%) reported a total of 114 suspected ARs,
      including 99 that occurred within 7 days post-vaccination. These results were
      consistent with the known safety profile of the two vaccines and did not show any
      change in reactogenicity or safety concerns. This passive ESS showed improved
      data reporting and demonstrated its suitability to health authorities'
      requirements; further fine tuning of the methodology is under discussion between
      all stakeholders.

PMID- 28494844
TI  - West Nile virus surveillance in Europe: moving towards an integrated animal-human
      vector approach.
AB  - This article uses the experience of five European countries to review the
      integrated approaches (human, animal and vector) for surveillance and monitoring
      of West Nile virus (WNV) at national and European levels. The epidemiological
      situation of West Nile fever in Europe is heterogeneous. No model of surveillance
      and monitoring fits all, hence this article merely encourages countries to
      implement the integrated approach that meets their needs. Integration of
      surveillance and monitoring activities conducted by the public health
      authorities, the animal health authorities and the authorities in charge of
      vector surveillance and control should improve efficiency and save resources by
      implementing targeted measures. The creation of a formal interagency working
      group is identified as a crucial step towards integration. Blood safety is a key
      incentive for public health authorities to allocate sufficient resources for WNV
      surveillance, while the facts that an effective vaccine is available for horses
      and that most infected animals remain asymptomatic make the disease a lesser
      priority for animal health authorities. The examples described here can support
      other European countries wishing to strengthen their WNV surveillance or
      preparedness, and also serve as a model for surveillance and monitoring of other
      (vector-borne) zoonotic infections.

PMID- 28494845
TI  - Monitoring influenza virus susceptibility to oseltamivir using a new rapid assay,
      iART.
AB  - A new rapid assay for detecting oseltamivir resistance in influenza virus, iART,
      was used to test 149 clinical specimens. Results were obtained for 132, with iART
      indicating 41 as 'resistant'. For these, sequence analysis found known and
      suspected markers of oseltamivir resistance, while no such markers were detected
      for the remaining 91 samples. Viruses isolated from the 41 specimens showed
      reduced or highly reduced inhibition by neuraminidase inhibition assay. iART may
      facilitate broader antiviral resistance testing.

PMID- 28494846
TI  - Can a science-based definition of acupuncture improve clinical outcomes?
AB  - Research on acupuncture has been muddled by attempts to bridge the ancient with
      the modern. Barriers to effectiveness research are reflected in recurring
      conflicts that include disagreement on use of the most basic terms, lack of
      standard intervention controls, and the absence of functional measures for
      assessing treatment effect. Acupuncture research has stalled at the "placebo
      barrier" wherein acupuncture is "no better than placebo." The most widely
      recognized comparative effectiveness research in acupuncture does not compare
      acupuncture treatment protocols within groups, thereby, mutating large scale
      effectiveness studies into large scale efficacy trials. Too often research in
      acupuncture attempts to tie outcomes to traditional belief systems thereby
      limiting usefulness of the research. The acupuncture research paradigm needs to
      focus more closely on a scientific definition of treatments and outcomes that
      compare protocols in terms of prevalent clinical issues such as relative
      effectiveness for treating pain.

PMID- 28494847
TI  - History of cupping (Hijama): a narrative review of literature.
AB  - Cupping (Hijama in Arabic) is an ancient, holistic method for the treatment of a
      variety of diseases. Though the exact origin of cupping therapy is a matter of
      controversy, its use has been documented in early Egyptian and Chinese medical
      practices. Diverse human civilizations have contributed to the historical
      development and continuation of cupping therapy. This narrative review describes
      the history of cupping, historical definitions, cupping instruments and uses of
      cupping therapy. Electronic searches of relevant databases (PubMed, Google
      Scholar and OvidSP) were conducted using keywords and Boolean operators. Manual
      searches and references of published articles and books were also conducted. A
      number of articles (N = 625) were retained for extensive review, and finally 83
      articles were included in this paper. The historical descriptions of cupping
      therapy were found in ancient human civilizations of the Eastern and Western
      world. There were inconsistent data concerning the origin of cupping,
      definitions, instruments, procedures, definite advancements and research in
      Hijama over centuries. Cupping therapy fell out of favor in 17th and mid-18th
      centuries but recovered popularity in modern medicine. Currently, cupping therapy
      is used for health promotion, prophylaxis and treatment of a variety of diseases
      around the world. Cupping therapy with a good safety profile has a checkered
      history and is a well-recognized traditional method for managing medical
      conditions. Currently, the scope of cupping therapy is expanding, and a growing
      body of research is providing additional evidence-based data for the further
      advancement of cupping therapy in the treatment of a variety of diseases.

PMID- 28494848
TI  - Standards of Reporting Kampo Products (STORK) in research articles.
AB  - There had been no standardized rules for citing ethical Kampo products used in
      clinical trials in journal articles. Although the name of a Kampo manufacturer
      was described in 77.9% of research articles, the name and ratios of crude drug
      components of Kampo formulas were not described in 77.5% of these papers.
      Considering the importance of proper characterization of interventions in the
      Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose
      the use of the Standards of Reporting Kampo Products (STORK) website,
      http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will
      provide an official source on the internet for verified information on individual
      Kampo formulations for citation purposes in clinical research articles.

PMID- 28494849
TI  - Identification and classification of traditional Chinese medicine syndrome types
      among senior patients with vascular mild cognitive impairment using latent tree
      analysis.
AB  - OBJECTIVE: To treat patients with vascular mild cognitive impairment (VMCI) using
      traditional Chinese medicine (TCM), it is necessary to classify the patients into
      TCM syndrome types and to apply different treatments to different types. In this
      paper, we investigate how to properly carry out the classification for patients
      with VMCI aged 50 or above using a novel data-driven method known as latent tree
      analysis (LTA). METHOD: A cross-sectional survey on VMCI was carried out in
      several regions in Northern China between February 2008 and February 2012 which
      resulted in a data set that involves 803 patients and 93 symptoms. LTA was
      performed on the data to reveal symptom co-occurrence patterns, and the patients
      were partitioned into clusters in multiple ways based on the patterns. The
      patient clusters were matched up with syndrome types, and population statistics
      of the clusters are used to quantify the syndrome types and to establish
      classification rules. RESULTS: Eight syndrome types are identified: Qi
      deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire
      heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence
      characteristics of each syndrome type are determined. Quantitative classification
      rules are established for determining whether a patient belongs to each of the
      syndrome types. CONCLUSION: A solution for the TCM syndrome classification
      problem for patients with VMCI and aged 50 or above is established based on the
      LTA of unlabeled symptom survey data. The results can be used as a reference in
      clinic practice to improve the quality of syndrome differentiation and to reduce
      diagnosis variances across physicians. They can also be used for patient
      selection in research projects aimed at finding biomarkers for the syndrome types
      and in randomized control trials aimed at determining the efficacy of TCM
      treatments of VMCI.

PMID- 28494850
TI  - Efficacy of a traditional Persian medicine preparation for radiation-induced
      xerostomia: a randomized, open-label, active-controlled trial.
AB  - BACKGROUND: Xerostomia is one of the most common side effects of radiation
      therapy among patients with head and neck cancers (HNC). However, conventional
      medicine lacks an effective treatment for radiation-induced xerostomia.
      OBJECTIVE: Synthesizing the traditional use of Alcea digitata and Malva
      sylvestris with their known beneficial effects from recent studies, we evaluated
      the efficacy of the herbs in the quality of life (QOL) of HNC patients with
      radiation-induced xerostomia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
      This study is a randomized, double-arm, open-label active-controlled clinical
      trial. We evaluated the effect of A. digitata and M. sylvestris on QOL of HNC
      patients with radiation-induced xerostomia compared with Hypozalix (artificial
      saliva). Patients were enrolled from the Imam Hossein Hospital's oncology clinic
      in Shahid Beheshti University of Medical Sciences, Tehran, Iran. MAIN OUTCOME
      MEASURES: Primary outcome measures in this trial were changes in patients' QOL
      assessed by the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire, Head and Neck Module (EORTC QLQ-H&N 35). RESULTS:
      Between-group analysis showed that the intervention group patients obtained
      significantly lower (better) total EORTC QLQ-H&N 35 scores as compared to the
      control group at the end of the intervention period (P = 0.007). Mean scores of
      dry mouth of EORTC QLQ-H&N 35 was also significantly lower (better) in the
      intervention group as compared to the control group (P = 0.017). CONCLUSION:
      Traditional Persian medicine preparation of hollyhocks and common mallow should
      be considered as a suitable treatment for xerostomia and improving QOL in HNC
      patients with radiation-induced xerostomia. TRIAL REGISTRATION: The trial was
      registered in ClinicalTrials.gov with Identifier: NCT02854358.

PMID- 28494851
TI  - Effects of homoeopathic ultrahigh dilutions of Aconitum napellus on Baker's yeast
      induced fever in rabbits.
AB  - OBJECTIVE: To evaluate the effects of homoeopathic ultrahigh dilutions of
      Aconitum napellus in Baker's yeast-induced fever in rabbits. METHODS: Rabbits
      were divided into 4 groups and each group contained 6 rabbits. Baker's yeast
      suspension (20%) was injected subcutaneously. After fever induction, paracetamol
      and homoeopathic ultrahigh dilutions (A. napellus 200c and 1 000c) were given
      orally. Rectal temperature was measured with digital thermometer hourly. RESULTS:
      Fever was induced in all the rabbits after 4 hours of Baker's yeast
      administration. A. napellus 200c and 1000c significantly reduced the temperature
      (P < 0.05). In positive control, temperature decrease was more significant (P <
      0.001). CONCLUSION: The above findings indicate the effectiveness of ultrahigh
      dilutions of A. napellus in Baker's yeast-induced fever in rabbits. However, the
      effects were slower and less significant than standard medicine. Moreover, future
      research is required to know their mechanism of reducing temperature.

PMID- 28494852
TI  - Atomic force microscopy correlates antimetastatic potentials of HepG2 cell line
      with its redox/energy status: effects of curcumin and Khaya senegalensis.
AB  - OBJECTIVE: The fatality of cancer is mostly dependent on the possibility of
      occurrence of metastasis. Thus, if the development of metastasis can be prevented
      through novel therapeutic strategies targeted against this process, then the
      success of cancer treatment will drastically increase. In this study, therefore,
      we evaluated the antimetastatic potentials of an extract of Khaya senegalensis
      and curcumin on the metastatic liver cell line HepG2, and also assessed the
      anticancer property of the extract. METHODS: Cells were cultured and treated with
      graded concentrations of test substances for 24, 48, or 72 h with provisions made
      for negative controls. Treated cells were assessed as follows:
      nanotechnologically - atomic force microscopy (AFM) was used to determine cell
      stiffness; biochemically - cell cytotoxicity, glutathione level and adenosine
      triphosphate status, caspase activation and mitochondrial toxicity were
      considered; and microbiologically - a carrot disk assay was used to assess the
      anticancer property of the extract of K. senegalensis. RESULTS: Curcumin and K.
      senegalensis increased the cell stiffness by 2.6- and 4.0-fold respectively,
      indicating their antimetastatic effects. Corresponding changes in redox
      (glutathione level) and energy (adenosine triphosphate) status of the cells were
      also demonstrated. Further mechanistic studies indicated that curcumin was not
      mitotoxic in HepG2 cells unlike the K. senegalensis extract. In addition, the
      extract potently inhibited the Agrobacterium tumefaciens-induced genetic
      transformation based on carrot disk assay. CONCLUSION: Cell elasticity
      measurement data, using AFM, strongly suggested, for the first time, that both
      curcumin and the extract of K. senegalensis exhibited antimetastatic properties
      on HepG2 cells.

PMID- 28494853
TI  - In vitro antioxidant assessment and a rapid HPTLC bioautographic method for the
      detection of anticholinesterase inhibitory activity of Geophila repens.
AB  - OBJECTIVE: Geophila repens (L.) I. M. Johnst. (Rubiaceae), a small, creeping,
      perennial herb, is claimed to have memory-enhancing property. The goal of this
      study was to assess its antioxidant and anticholinesterase activity and conduct a
      rapid bioautographic enzyme assay for screening acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) inhibition of G. repens extracts. METHODS:
      Antioxidant activity of G. repens extracts was assessed by performing 1,1
      diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide (SOD), hydroxyl
      (OH) and total antioxidant capacity (TAC) assays. Anticholinesterase activity was
      investigated by quantifying the AChE and BChE inhibitory activities of chloroform
      (CGR), ethyl acetate (EGR) and methanol (MGR) extract fractions from G. repens
      leaves. A rapid high-performance thin-layer chromatography (HPTLC) bioautographic
      method for the detection of AChE and BChE inhibition was performed. RESULTS:
      Among all extract fractions, EGR exhibited the highest half maximal inhibitory
      concentration (IC50) in DPPH, SOD, NO, OH and TAC assays, with IC50 of (38.33 +/-
      3.21), (45.14 +/- 1.78), (59.81 +/- 1.32), (39.45 +/- 0.79) and (43.76 +/- 0.81)
      MUg/mL respectively. EGR displayed competitive, reversible inhibition of AChE and
      BChE activities with IC50 of (68.63 +/- 0.45) and (59.45 +/- 0.45) MUg/mL,
      respectively. Total phenolic and flavonoids contents of EGR were found to be
      360.42 mg gallic acid equivalents and 257.31 mg quercetin equivalents per gram of
      extract. Phytoconstituents of the EGR extract that were inhibitors of
      cholinesterase produced white spots on the yellow background of HPTLC plates in
      the bioautographic test. CONCLUSION: The results of this study revealed that
      phenols and flavonoids could be responsible for the antioxidant,
      anticholinesterase activities of G. repens.

PMID- 28494854
TI  - Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with
      cisplatin, inhibits growth of lung cancer cells through transforming growth
      factor-beta1 signaling pathway.
AB  - OBJECTIVE: To investigate the tumor inhibition effect of Yangfei Kongliu Formula
      (YKF), a compound Chinese herbal medicine, combined with cisplatin (DDP) and its
      action mechanisms. METHODS: C57BL/6 mice with Lewis lung carcinoma were divided
      into six groups: control group (C), DDP group (2 mg/kg, DDP), low-dose YKF group
      (2.43 g/kg, L), high-dose YKF group (24.3 g/kg, H), low-dose YKF combined with
      DDP group (L + DDP) and high-dose YKF combined with DDP group (H + DDP).
      Transforming growth factor-beta1 (TGF-beta1), mothers against decapentaplegic
      homolog 3 (Smad3) and Smad7 levels were measured with quantitative real-time
      polymerase chain reaction (qPCR), Western blotting and immunohistochemistry. An
      enzyme-linked immunosorbent assay was used to analyze the expressions of
      interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: YKF
      combined with DDP significantly inhibited the growth and metastasis of tumors
      relative to the control group, and YKF groups (P < 0.05). There was no
      significant difference between high-dose YKF group and low-dose YKF group (P >
      0.05). We also found that the expression levels of TGF-beta1 and Smad3 were both
      significantly decreased by YKF relative to the control group (P < 0.05).
      Furthermore, after treatment with YKF combined with DDP, the expression levels of
      TGF-beta1 and Smad3 were decreased but the expression level of Smad7 was
      increased relative to the DDP group (P < 0.05). Compared to the DDP group, the
      combination of YKF and DDP enhanced the effect of tumor inhibition (P < 0.05),
      showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased
      serum levels of IL-2 and TNF-alpha relative to the control group (P < 0.05).
      Furthermore, the expression levels of IL-2 and TNF-alpha were significantly
      decreased when treated with YKF in combination with DDP. Co-treatment with YKF
      and DDP significantly inhibited tumor growth, decreased the expressions of TGF
      beta1, Smad3, IL-2 and TNF-alpha and increased the expression of Smad7; these
      differences were significant relative to both YKF groups and the control group (P
      < 0.05). CONCLUSION: YKF can inhibit tumor growth synergistically with DDP,
      mainly through the TGF-beta1 signaling pathway.

PMID- 28494855
TI  - A complication of wet cupping therapy: vesiculobullous plaque on an erythematous
      base.

PMID- 28494856
TI  - Addressing the ethical issues raised by synthetic human entities with embryo-like
      features.
AB  - The "14-day rule" for embryo research stipulates that experiments with intact
      human embryos must not allow them to develop beyond 14 days or the appearance of
      the primitive streak. However, recent experiments showing that suitably cultured
      human pluripotent stem cells can self-organize and recapitulate embryonic
      features have highlighted difficulties with the 14-day rule and led to calls for
      its reassessment. Here we argue that these and related experiments raise more
      foundational issues that cannot be fixed by adjusting the 14-day rule, because
      the framework underlying the rule cannot adequately describe the ways by which
      synthetic human entities with embryo-like features (SHEEFs) might develop morally
      concerning features through altered forms of development. We propose that limits
      on research with SHEEFs be based as directly as possible on the generation of
      such features, and recommend that the research and bioethics communities lead a
      wide-ranging inquiry aimed at mapping out solutions to the ethical problems
      raised by them.

PMID- 28494857
TI  - Correction: Addressing the ethical issues raised by synthetic human entities with
      embryo-like features.

PMID- 28494858
TI  - mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis
      through Post-transcriptional Control of ATF4.
AB  - The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of
      cell growth that is commonly deregulated in human diseases. Here we find that
      mTORC1 controls a transcriptional program encoding amino acid transporters and
      metabolic enzymes through a mechanism also used to regulate protein synthesis.
      Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element
      recognized by activating transcription factor 4 (ATF4), a key effector of the
      integrated stress response. ATF4 translation is normally induced by the
      phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) through a
      mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR.
      mTORC1 also controls ATF4 translation through uORFs, but independently of changes
      in eIF2alpha phosphorylation. mTORC1 instead employs the 4E-binding protein (4E
      BP) family of translation repressors. These results link mTORC1-regulated demand
      for protein synthesis with an ATF4-regulated transcriptional program that
      controls the supply of amino acids to the translation machinery.

PMID- 28494860
TI  - Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast
      Fate in Embryonic Stem Cells.
AB  - The first cell fate choice of the preimplantation embryo generates the
      extraembryonic trophoblast and embryonic epiblast lineages. Embryonic stem cells
      (ESCs) and trophoblast stem cells (TSCs) can be utilized to investigate molecular
      mechanisms of this first cell fate decision. It has been established that ESCs
      can be induced to acquire trophoblast lineage characteristics upon manipulation
      of lineage-determining transcription factors. Here, we have interrogated the
      potential of microRNAs (miRNAs) to drive trans-differentiation of ESCs into the
      trophoblast lineage. Analysis of gene expression data identified a network of TSC
      enriched miRNAs that were predicted to target mRNAs enriched in ESCs. Ectopic
      expression of these miRNAs in ESCs resulted in a stable trophoblast phenotype,
      supported by gene expression changes and in vivo contribution potential. This
      process is highly miRNA-specific and dependent on Hdac2 inhibition. Our
      experimental evidence suggests that these miRNAs promote a mural trophectoderm
      (TE)-like cell fate with physiological properties that differentiate them from
      the polar TE.

PMID- 28494859
TI  - HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue
      Destructive Phenotype.
AB  - While highly active anti-retroviral therapy has dramatically improved the
      survival of HIV-infected individuals, there is an increased risk for other co
      morbidities, such as COPD, manifesting as emphysema. Given that emphysema
      originates around the airways and that human airway basal cells (BCs) are adult
      airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a
      distinct phenotype that contributes to the development of emphysema. Our data
      indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs
      induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9
      expression through activation of MAPK signaling pathways. This HIV-induced
      "destructive" phenotype may contribute to degradation of extracellular matrix and
      tissue damage relevant to the development of emphysema commonly seen in HIV+
      individuals.

PMID- 28494861
TI  - Excitatory Microcircuits within Superficial Layers of the Medial Entorhinal
      Cortex.
AB  - The distinctive firing pattern of grid cells in the medial entorhinal cortex
      (MEC) supports its role in the representation of space. It is widely believed
      that the hexagonal firing field of grid cells emerges from neural dynamics that
      depend on the local microcircuitry. However, local networks within the MEC are
      still not sufficiently characterized. Here, applying up to eight simultaneous
      whole-cell recordings in acute brain slices, we demonstrate the existence of
      unitary excitatory connections between principal neurons in the superficial
      layers of the MEC. In particular, we find prevalent feed-forward excitation from
      pyramidal neurons in layer III and layer II onto stellate cells in layer II,
      which might contribute to the generation or the inheritance of grid cell
      patterns.

PMID- 28494862
TI  - Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance
      via a Neuronal Ca2+ Sensor Protein.
AB  - Excitation-inhibition imbalance in neural networks is widely linked to
      neurological and neuropsychiatric disorders. However, how genetic factors alter
      neuronal activity, leading to excitation-inhibition imbalance, remains unclear.
      Here, using the C. elegans locomotor circuit, we examine how altering neuronal
      activity for varying time periods affects synaptic release pattern and animal
      behavior. We show that while short-duration activation of excitatory cholinergic
      neurons elicits a reversible enhancement of presynaptic strength, persistent
      activation results to asynchronous and reduced cholinergic drive, inducing
      imbalance between endogenous excitation and inhibition. We find that the neuronal
      calcium sensor protein NCS-2 is required for asynchronous cholinergic release in
      an activity-dependent manner and dampens excitability of inhibitory neurons non
      cell autonomously. The function of NCS-2 requires its Ca2+ binding and membrane
      association domains. These results reveal a synaptic mechanism implicating
      asynchronous release in regulation of excitation-inhibition balance.

PMID- 28494864
TI  - Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the
      Neonatal Auditory Cortex.
AB  - GABAergic activity is important in neocortical development and plasticity.
      Because the maturation of GABAergic interneurons is regulated by neural activity,
      the source of excitatory inputs to GABAergic interneurons plays a key role in
      development. We show, by laser-scanning photostimulation, that layer 4 and layer
      5 GABAergic interneurons in the auditory cortex in neonatal mice (<P7) receive
      extensive translaminar glutamatergic input via NMDAR-only synapses. Extensive
      translaminar AMPAR-mediated input developed during the second postnatal week,
      whereas NMDAR-only presynaptic connections decreased. GABAergic interneurons
      showed two spatial patterns of translaminar connection: inputs originating
      predominantly from supragranular or from supragranular and infragranular layers,
      including the subplate, which relays early thalamocortical activity. Sensory
      deprivation altered the development of translaminar inputs. Thus, distinct
      translaminar circuits to GABAergic interneurons exist throughout development, and
      the maturation of excitatory synapses is input-specific. Glutamatergic signaling
      from subplate and intracortical sources likely plays a role in the maturation of
      GABAergic interneurons.

PMID- 28494863
TI  - Multiplexed Spike Coding and Adaptation in the Thalamus.
AB  - High-frequency "burst" clusters of spikes are a generic output pattern of many
      neurons. While bursting is a ubiquitous computational feature of different
      nervous systems across animal species, the encoding of synaptic inputs by bursts
      is not well understood. We find that bursting neurons in the rodent thalamus
      employ "multiplexing" to differentially encode low- and high-frequency stimulus
      features associated with either T-type calcium "low-threshold" or fast sodium
      spiking events, respectively, and these events adapt differently. Thus, thalamic
      bursts encode disparate information in three channels: (1) burst size, (2) burst
      onset time, and (3) precise spike timing within bursts. Strikingly, this latter
      "intraburst" encoding channel shows millisecond-level feature selectivity and
      adapts across statistical contexts to maintain stable information encoded per
      spike. Consequently, calcium events both encode low-frequency stimuli and, in
      parallel, gate a transient window for high-frequency, adaptive stimulus encoding
      by sodium spike timing, allowing bursts to efficiently convey fine-scale temporal
      information.

PMID- 28494865
TI  - Transformation of Astrocytes to a Neuroprotective Phenotype by Microglia via P2Y1
      Receptor Downregulation.
AB  - Microglia and astrocytes become reactive following traumatic brain injury (TBI).
      However, the coordination of this reactivity and its relation to pathophysiology
      are unclear. Here, we show that microglia transform astrocytes into a
      neuroprotective phenotype via downregulation of the P2Y1 purinergic receptor. TBI
      initially caused microglial activation in the injury core, followed by reactive
      astrogliosis in the peri-injured region and formation of a neuroprotective
      astrocyte scar. Equivalent changes to astrocytes were observed in vitro after
      injury. This change in astrocyte phenotype resulted from P2Y1 receptor
      downregulation, mediated by microglia-derived cytokines. In mice, astrocyte
      specific P2Y1 receptor overexpression (Astro-P2Y1OE) counteracted scar formation,
      while astrocyte-specific P2Y1 receptor knockdown (Astro-P2Y1KD) facilitated scar
      formation, suggesting critical roles of P2Y1 receptors in the transformation.
      Astro-P2Y1OE and Astro-P2Y1KD mice showed increased and reduced neuronal damage,
      respectively. Altogether, our findings indicate that microglia-astrocyte
      interaction, involving a purinergic signal, is essential for the formation of
      neuroprotective astrocytes.

PMID- 28494866
TI  - Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating
      Local Lymphocyte Activation.
AB  - Mucosal tissues are constantly in direct contact with diverse beneficial and
      pathogenic microbes, highlighting the need for orchestrating complex microbial
      signals to sustain effective host defense. Here, we show an essential role for
      intestinal epithelial cell expression of histone deacetylase 3 (HDAC3) in
      responding to pathogenic microbes and activating protective innate immunity. Mice
      lacking HDAC3 in intestinal epithelial cells were more susceptible to Citrobacter
      rodentium when under tonic stimulation by the commensal microbiota. This impaired
      host defense reflected significantly decreased IFNgamma production by
      intraepithelial CD8+ T cells early during infection. Further, HDAC3 was necessary
      for infection-induced epithelial expression of the IFNgamma-inducing factor IL
      18, and administration of IL-18 restored IFNgamma activity to resident CD8+ T
      cells and reduced infection. Thus, HDAC3 mediates communication between
      intestinal epithelial cells and resident lymphocytes, revealing that epithelial
      priming by an epigenetic modifier may direct mucosal regulation of host defense
      against pathogenic microbes.

PMID- 28494867
TI  - Essential Roles of SATB1 in Specifying T Lymphocyte Subsets.
AB  - T cell receptor (TCR) signaling by MHC class I and II induces thymocytes to
      acquire cytotoxic and helper fates via the induction of Runx3 and ThPOK
      transcription factors, respectively. The mechanisms by which TCR signaling is
      translated into transcriptional programs for each cell fate remain elusive. Here,
      we show that, in post-selection thymocytes, a genome organizer, SATB1, activates
      genes for lineage-specifying factors, including ThPOK, Runx3, CD4, CD8, and Treg
      factor Foxp3, via regulating enhancers in these genes in a locus-specific manner.
      Indeed, SATB1-deficient thymocytes are partially re-directed into inappropriate T
      lineages after both MHC class I- and II-mediated selection, and they fail to
      generate NKT and Treg subsets. Despite its essential role in activating enhancers
      for the gene encoding ThPOK in TCR-signaled thymocytes, SATB1 becomes dispensable
      for maintaining ThPOK in CD4+ T cells. Collectively, our findings demonstrate
      that SATB1 shapes the primary T cell pool by directing lineage-specific
      transcriptional programs in the thymus.

PMID- 28494868
TI  - Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression.
AB  - PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be
      induced in tumors by interferon exposure, leading to immune evasion. This process
      is important for immunotherapy based on PD-1 blockade. We examined the specific
      molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2
      expression in melanoma cells. These studies revealed that the interferon-gamma
      JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with
      IRF1 binding to its promoter. PD-L2 responded equally to interferon beta and
      gamma and is regulated through both IRF1 and STAT3, which bind to the PD-L2
      promoter. Analysis of biopsy specimens from patients with melanoma confirmed
      interferon signature enrichment and upregulation of gene targets for
      STAT1/STAT2/STAT3 and IRF1 in anti-PD-1-responding tumors. Therefore, these
      studies map the signaling pathway of interferon-gamma-inducible PD-1 ligand
      expression.

PMID- 28494869
TI  - Mitochondrial ROS Production Protects the Intestine from Inflammation through
      Functional M2 Macrophage Polarization.
AB  - Mitochondria are signaling hubs in cellular physiology that play a role in
      inflammatory diseases. We found that partial inhibition of the mitochondrial ATP
      synthase in the intestine of transgenic mice triggers an anti-inflammatory
      response through NFkappaB activation mediated by mitochondrial mtROS. This
      shielding phenotype is revealed when mice are challenged by DSS-induced colitis,
      which, in control animals, triggers inflammation, recruitment of M1 pro
      inflammatory macrophages, and the activation of the pro-oncogenic STAT3 and
      Akt/mTOR pathways. In contrast, transgenic mice can polarize macrophages to the
      M2 anti-inflammatory phenotype. Using the mitochondria-targeted antioxidant MitoQ
      to quench mtROS in vivo, we observe decreased NFkappaB activation, preventing its
      cellular protective effects. These findings stress the relevance of mitochondrial
      signaling to the innate immune system and emphasize the potential role of the ATP
      synthase as a therapeutic target in inflammatory and other related diseases.

PMID- 28494870
TI  - Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic
      Perturbations.
AB  - Microbes have shown a remarkable ability in evading the killing actions of
      antimicrobial agents, such that treatment of bacterial infections represents once
      more an urgent global challenge. Understanding the initial bacterial response to
      antimicrobials may reveal intrinsic tolerance mechanisms to antibiotics and
      suggest alternative and less conventional therapeutic strategies. Here, we used
      mass spectrometry-based metabolomics to monitor the immediate metabolic response
      of Escherichia coli to a variety of antibiotic perturbations. We show that rapid
      metabolic changes can reflect drug mechanisms of action and reveal the active
      role of metabolism in mediating the first stress response to antimicrobials. We
      uncovered a role for ammonium imbalance in aggravating chloramphenicol toxicity
      and the essential function of deoxythymidine 5'-diphosphate (dTDP)-rhamnose
      synthesis for the immediate transcriptional upregulation of GyrA in response to
      quinolone antibiotics. Our results suggest bacterial metabolism as an attractive
      target to interfere with the early bacterial response to antibiotic treatments
      and reduce the probability for survival and eventual evolution of antibiotic
      resistance.

PMID- 28494872
TI  - Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance.
AB  - Proviral factors are host proteins hijacked by viruses for processes essential
      for virus propagation such as cellular entry and replication. Pathogens and their
      hosts co-evolve. It follows that replacing a proviral factor with a functional
      ancestral form of the same protein could prevent viral propagation without
      fatally compromising organismal fitness. Here, we provide proof of concept of
      this notion. Thioredoxins serve as general oxidoreductases in all known cells. We
      report that several laboratory resurrections of Precambrian thioredoxins display
      substantial levels of functionality within Escherichia coli. Unlike E. coli
      thioredoxin, however, these ancestral thioredoxins are not efficiently recruited
      by the bacteriophage T7 for its replisome and therefore prevent phage propagation
      in E. coli. These results suggest an approach to the engineering of virus
      resistance. Diseases caused by viruses may have a devastating effect in
      agriculture. We discuss how the suggested approach could be applied to the
      engineering of plant virus resistance.

PMID- 28494871
TI  - miRNA-32 Drives Brown Fat Thermogenesis and Trans-activates Subcutaneous White
      Fat Browning in Mice.
AB  - Brown adipose tissue (BAT) activation and subcutaneous white fat browning are
      essential components of the thermogenic response to cold stimulus in mammals.
      microRNAs have been shown to regulate both processes in cis. Here, we identify
      miR-32 as a BAT-specific super-enhancer-associated miRNA in mice that is
      selectively expressed in BAT and further upregulated during cold exposure.
      Inhibiting miR-32 in vivo led to impaired cold tolerance, decreased BAT
      thermogenesis, and compromised white fat browning as a result of reduced serum
      FGF21 levels. Further examination showed that miR-32 directly represses its
      target gene Tob1, thereby activating p38 MAP kinase signaling to drive FGF21
      expression and secretion from BAT. BAT-specific miR-32 overexpression led to
      increased BAT thermogenesis and serum FGF21 levels, which further promotes white
      fat browning in trans. Our results suggested miR-32 and Tob1 as modulators of
      FGF21 signaling that can be manipulated for therapeutic benefit against obesity
      and metabolic syndrome.

PMID- 28494873
TI  - A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking
      In Vivo.
AB  - EGF receptor (EGFR) is a critical signaling node throughout life. However, it has
      not been possible to directly visualize endogenous Egfr in mice. Using
      CRISPR/Cas9 genome editing, we appended a fluorescent reporter to the C terminus
      of the Egfr. Homozygous reporter mice appear normal and EGFR signaling is intact
      in vitro and in vivo. We detect distinct patterns of Egfr expression in
      progenitor and differentiated compartments in embryonic and adult mice. Systemic
      delivery of EGF or amphiregulin results in markedly different patterns of Egfr
      internalization and trafficking in hepatocytes. In the normal intestine, Egfr
      localizes to the crypt rather than villus compartment, expression is higher in
      adjacent epithelium than in intestinal tumors, and following colonic injury
      expression appears in distinct cell populations in the stroma. This reporter,
      under control of its endogenous regulatory elements, enables in vivo monitoring
      of the dynamics of Egfr localization and trafficking in normal and disease
      states.

PMID- 28494875
TI  - C/EBPalpha Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma
      and Leukemia Cell Lines and Impairs Their Tumorigenicity.

PMID- 28494874
TI  - Molecular-Subtype-Specific Biomarkers Improve Prediction of Prognosis in
      Colorectal Cancer.
AB  - Colorectal cancer (CRC) is characterized by major inter-tumor diversity that
      complicates the prediction of disease and treatment outcomes. Recent efforts help
      resolve this by sub-classification of CRC into natural molecular subtypes;
      however, this strategy is not yet able to provide clinicians with improved tools
      for decision making. We here present an extended framework for CRC stratification
      that specifically aims to improve patient prognostication. Using transcriptional
      profiles from 1,100 CRCs, including >300 previously unpublished samples, we
      identify cancer cell and tumor archetypes and suggest the tumor microenvironment
      as a major prognostic determinant that can be influenced by the microbiome.
      Notably, our subtyping strategy allowed identification of archetype-specific
      prognostic biomarkers that provided information beyond and independent of UICC
      TNM staging, MSI status, and consensus molecular subtyping. The results
      illustrate that our extended subtyping framework, combining subtyping and subtype
      specific biomarkers, could contribute to improved patient prognostication and may
      form a strong basis for future studies.

PMID- 28494876
TI  - Comparing performance of Fastrach ILMA vs flexible bronchoscope for awake
      intubation.

PMID- 28494877
TI  - Prevalence of malignant hyperthermia diagnosis in hospital discharge records in
      California, Florida, New York, and Wisconsin.
AB  - STUDY OBJECTIVE: Malignant hyperthermia (MH) is a rare yet potentially fatal
      pharmacogenetic disorder triggered by exposure to inhalational anesthetics and
      the depolarizing neuromuscular blocking agent succinylcholine. Epidemiologic data
      on the geographic variation in MH prevalence is scant. The objective of this
      study is to examine the prevalence of recorded MH diagnosis in patients
      discharged from hospitals in four states in the United States. DESIGN:
      Observational study. SETTING: Healthcare Cost and Utilization Project (HCUP)
      State Inpatient Database (SID) for California (2011), Florida (2011), New York
      (2012) and Wisconsin (2012). PATIENTS: A total of 164 hospital discharges that
      had a recorded diagnosis of MH using the International Classification of Disease,
      9th Revision, Clinical Modification code 995.86. METHODS: MH prevalence was
      assessed by patient demographic and clinical characteristics. MAIN RESULTS: The
      prevalence of MH per 100,000 hospital discharges ranged from 1.23 (95% Confidence
      Interval [CI], 0.80-1.66) in New York to 1.91 (95% CI, 1.48-2.34) in California,
      and the prevalence of MH per 100,000 surgical discharges ranged from 1.47 (95%
      CI, 0.93-2.02) in New York to 2.86 (95% CI, 2.00-3.71) in Florida. The prevalence
      of MH in male patients was more than twice the prevalence in female patients. Of
      the 164 patients with MH diagnosis, 11% were dead on discharge. CONCLUSIONS:
      There exists a modest variation in the prevalence of recorded MH diagnosis in
      hospital discharges in California, Florida, New York and Wisconsin. Epidemiologic
      patterns of MH diagnosis in hospital discharges appear to be similar across the
      four states. Further research is needed to better understand the geographic
      variation and contributing factors of MH in different populations.

PMID- 28494879
TI  - Could Brugada Syndrome complicate anesthesia?

PMID- 28494878
TI  - Factors influencing postoperative pain following discharge in pediatric
      ambulatory surgery patients.
AB  - STUDY OBJECTIVE: To identify demographic, intraoperative, and parental factors
      that influence the postoperative pain experience in ambulatory surgery pediatric
      patients. We also monitored postoperative maladaptive behavior changes (PMBCs) to
      investigate the relationship between pain and PMBCs. DESIGN: Prospective cohort
      study. SETTING: Discharge period after ambulatory surgery. PATIENTS: 204 patients
      ages 1-6years undergoing ambulatory orthopedic, urology, general surgery, and
      otolaryngology surgical procedures who were American Society of Anesthesiologists
      (ASA) physical status I or II. INTERVENTIONS: None. MEASUREMENTS: We administered
      telephone questionnaires to parents of ambulatory surgery patients 1-6years old
      exploring pain ratings, behavior change ratings, and medication compliance at 2
      3days and 1-2weeks after surgery. Pain and behavioral change scores were obtained
      using the Parents Postoperative Pain Measure (PPPM) and Post-Hospital Behavior
      Questionnaire (PHBQ). Parental medication compliance was defined as parents who
      followed the discharge instructions for pain medication administration. MAIN
      RESULTS: For our cohort, 69% of patients experienced pain after 2-3days and 17%
      after 1-2weeks post-discharge. PMBCs were reported in 55% after 2-3days, and in
      15% after 1-2weeks. In addition, PMBCs occurred in the absence of pain (PPPM=0)
      at rates of 20% and 5% at 2-3days and 1-2weeks after surgery, respectively.
      Female sex, anesthesia duration, and otolaryngology procedures correlated with
      higher postoperative pain (PPPM) scores in univariate and multivariate analysis.
      Intraoperative medications did not correlate with PPPM or PHBQ scores. Higher
      pain scores were associated with parents who were compliant with discharge
      instructions for pain medications. CONCLUSIONS: Many pediatric patients
      experienced short-term pain and PMBCs after ambulatory surgery, but these largely
      resolved by 1-2weeks following discharge. Patient sex, anesthesia duration, and
      surgical procedure influenced postoperative pain and/or PMBCs. Furthermore, PMBCs
      were associated with, but not solely a manifestation of, postoperative pain.

PMID- 28494880
TI  - Noninvasive mechanical ventilation during spontaneous breathing anaesthesia: Can
      electrical impedance tomography be a useful bedside tool to titrate PEEP level?

PMID- 28494881
TI  - Effective nasal mask ventilation of a difficult airway in a patient with advanced
      salivary gland cancer.

PMID- 28494882
TI  - Use of the Laryngeal Mask Airway (LMA) ProtectorTM for shoulder surgeries in
      beach-chair position.

PMID- 28494883
TI  - Optimal timing for telescoping endotracheal tube into an introducer during
      nasotracheal intubation.

PMID- 28494884
TI  - Less postoperative sore throat after nasotracheal intubation using a fiberoptic
      bronchoscope than using a Macintosh laryngoscope: A double-blind, randomized,
      controlled study.
AB  - STUDY OBJECTIVE: To evaluate whether nasotracheal intubation using a fiberoptic
      bronchoscope reduces postoperative sore throat. DESIGN: Prospective, double
      blinded, randomized, and controlled study. SETTING: Postoperative areas and
      surgical ward of a university hospital. PATIENTS: Seventy-four patients with
      American Society of Anesthesiologists physical status I-II who were scheduled for
      elective general anesthesia requiring nasotracheal intubation. INTERVENTIONS:
      Patients were randomized to one of two intubation groups, F (fiberoptic
      bronchoscope-guided) and M (Macintosh laryngoscope-guided), and after induction
      of general anesthesia, the patients' tracheas were intubated via the nose.
      MEASUREMENTS: The intensity of postoperative sore throat was evaluated using a
      numerical rating score (0=none, 10=severe) at 24 hours postoperatively, and the
      incidence of nasal mucosal trauma, time to completion of intubation, and
      hemodynamic responses were recorded and compared between groups. MAIN RESULTS:
      The numerical rating score value was significantly lower in group F than in group
      M (P=.0047), but the incidence of nasal mucosal trauma was comparable between the
      two groups. The median time to completion of intubation was shorter for group F
      than group M (P<.0001). Hemodynamic responses were not significantly different.
      CONCLUSIONS: Fiberoptic bronchoscope-guided intubation is associated with less
      sore throat after nasotracheal intubation than M intubation. The time to
      completion of intubation was significantly shorter using the fiberoptic
      bronchoscope than that using the Macintosh laryngoscope.

PMID- 28494885
TI  - Importance of relying on examples for both anesthesiologists and other physicians
      to assign unbiased American Society of Anesthesiologists Physical Status
      Classifications.

PMID- 28494886
TI  - Determining predictive value of preoperative tests for difficult intubation.

PMID- 28494887
TI  - Preoperative risk stratification of critically ill patients.
AB  - STUDY OBJECTIVE: Risk assessment historically emphasized cardiac morbidity and
      mortality in elective, outpatient, non-cardiac surgery. However, critically ill
      patients increasingly present for therapeutic interventions. Our study
      investigated the relationship of American Society of Anesthesiologists (ASA)
      class, revised cardiac risk index (RCRI), and sequential organ failure assessment
      (SOFA) score with survival to discharge in critically ill patients with
      respiratory failure. DESIGN: Retrospective cohort analysis over a 21-month
      period. SETTING: Five adult intensive care units (ICUs) at a single tertiary
      medical center. PATIENTS: Three hundred fifty ICU patients in respiratory
      failure, who underwent 501 procedures with general anesthesia. MEASUREMENTS:
      Demographic, clinical, and surgical variables were collected from the pre
      anesthesia evaluation forms and preoperative ICU charts. The primary outcome was
      survival to discharge. MAIN RESULTS: Ninety-six patients (27%) did not survive to
      discharge. There were significant differences between survivors and non-survivors
      for ASA (3.7 vs. 3.9, p=0.001), RCRI (1.6 vs. 2.0, p=0.003), and SOFA score (8.1
      vs. 11.2, p<0.001). Based on the area under the receiver operating characteristic
      curve for these relationships, there was only modest discrimination between the
      groups, ranging from the most useful SOFA (0.68) to less useful RCRI (0.60) and
      ASA (0.59). CONCLUSIONS: This single center retrospective study quantified a high
      perioperative risk for critically ill patients with advanced airways: one in four
      did not survive to discharge. Preoperative ASA score, RCRI, and SOFA score only
      partially delineated survivors and non-survivors. Given the existing limitations,
      future research may identify assessment tools more relevant to discriminating
      survival outcomes for critically ill patients in the perioperative environment.

PMID- 28494888
TI  - Cerebral infarction in cervical plexus block.

PMID- 28494889
TI  - Influence of the perioperative administration of magnesium sulfate on the total
      dose of anesthetics during general anesthesia. A systematic review and meta
      analysis.
AB  - BACKGROUND: Magnesium sulfate displays numerous characteristics that make it a
      useful drug in anesthesiology (N-methyl-d-aspartate receptor antagonist,
      vasodilator, antiarrhythmic, inhibitor of catecholamine release and of
      acetylcholine in the terminal motor plate). The perioperative use of this drug as
      an adjuvant capable of decreasing the required dose of anesthetics, has been
      proposed. OBJECTIVES: To assess the influence of intravenous magnesium sulfate
      administration during general anesthesia on the overall dose of required
      anesthetics. DESIGN: A systematic review of controlled randomized trials and meta
      analysis. DATA SOURCES: An electronic bibliography search in MEDLINE and in the
      Cochrane Database of Controlled trials (CENTRAL) up to 2015. STUDY ELIGIBILITY
      CRITERIA, PARTICIPANTS AND INTERVENTIONS: Randomized, double-blind trials
      relating to general anesthesia in elective surgery using intravenous magnesium
      sulfate that provide information about the anesthetic requirements in ASA I and
      II patients. RESULTS: 20 clinical trials were selected for the qualitative
      analysis and 19 for the quantitative one. The use of perioperative intravenous
      magnesium sulfate reduces the requirement of the anesthetic, propofol during
      induction (-28.52mg; CI 95% -35.22-1.82; p<0.001) and maintenance (-213.56mg; CI
      95% -322.93, -104.18; p<0.001) of anesthesia. Additionally, magnesium sulfate
      reduces the requirement of neuromuscular non-despolarizing blocking agents (
      2.99mg; CI 95% -44.47, -1.99; p<0.001) and the intraoperative consumption of
      fentanile(-53.57 mcg; CI 95% -75.01, -32.12; p<0.001). CONCLUSIONS: We conclude
      that perioperative magnesium sulfate acts as a coadjuvant drug capable of
      reducing anesthetic requirements.

PMID- 28494890
TI  - The predictive value of pre-recruitment achievement on resident performance in
      anesthesiology.
AB  - STUDY OBJECTIVE: Selecting candidates for residency positions is challenging and
      there is little research on the correlation between commonly used selection
      criteria and subsequent performance in anesthesiology. This study examined the
      association between the selection measures and post-recruitment performance in
      residency. DESIGN: Retrospective review of archival data. SETTING: Anesthesiology
      residency program at a large academic anesthesiology department. SUBJECTS:
      Residents who were matched to the anesthesiology program over 9years (graduation
      classes of 2006 to 2014). INTERVENTIONS: None. MEASUREMENTS: The pre-recruitment
      achievements included a comprehensive list of measures obtained from residents'
      application portfolios in conjunction with interview performance. The post
      recruitment examination outcomes consisted of the in-training examination (ITE)
      scores in the three clinical anesthesia (CA) years and first-attempt success on
      the written board certification examination administered by the American Board of
      Anesthesiology (ABA). Scholarly output during residency was measured by
      publication record. Clinical performance at the conclusion of residency was
      independently rated by three faculty members. Bivariate analysis and regression
      models were conducted to examine association between predictors and outcomes.
      MAIN RESULTS: High United States Medical Licensing Examination (USMLE) scores,
      class rank in medical school and interview performance were predictive of high
      examination scores in residency and good clinical performance. Class rank
      appeared to be the best predictor of scholarly publication and pursuing an
      academic career beyond residency. CONCLUSIONS: Comparative performance with
      classmates (i.e., class rank) in medical school appeared to be an effective
      predictor of overall performance in residency, which warrants more attention in
      future study. Although interview performance is subject to recruitment team
      members' interpretation, it is an important measure to include in recruitment
      decisions.

PMID- 28494891
TI  - Clinical experiences of ultrasound-guided lateral thoracolumbar Interfascial
      plane (TLIP) block.

PMID- 28494892
TI  - Postoperative analgesic efficacy of single-shot and continuous transversus
      abdominis plane block after laparoscopic cholecystectomy: A randomized controlled
      clinical trial.
AB  - STUDY OBJECTIVE: To compare the analgesic efficacy of ultrasound-guided single
      shot and continuous transversus abdominis plane (TAP) block to that of IV-PCA in
      patients undergoing laparoscopic cholecystectomy. DESIGN: Prospective randomized
      controlled trial. SETTING: Post-anesthesia care unit and General ward. PATIENTS:
      108 American Society of Anesthesiologist (ASA) physical status I-II patients
      undergoing laparoscopic cholecystectomy. INTERVENTIONS: Group A received IV-PCA;
      group B received both ultrasound-guided single-shot TAP block with 0.2%
      ropivacaine (20mL) and IV-PCA; and group C received continuous TAP block using an
      ultrasound-guidance-inserted indwelling catheter. In group C, infusion of 0.2%
      ropivacaine at a basal rate of 3mL/h, bolus dose of 4mL, and a lockout interval
      of 30min was maintained for 48h postoperatively. The primary outcome was
      evaluated analgesic efficacy using the numeric rating scale (NRS) for 48h
      postoperatively. Other outcomes included the number of patients requiring
      additional analgesics, patient satisfaction with postoperative pain control, and
      incidence of postoperative adverse events. MAIN RESULTS: Compared to other
      groups, group C had higher deep abdominal NRS at 1h postoperatively (P<0.05), and
      lower incidence of postoperative urinary retention (P<0.05). There were no
      significant intergroup differences in the number of patients requiring additional
      analgesics, and patient satisfaction with postoperative pain control.
      CONCLUSIONS: Compared to IV-PCA with or without single-shot TAP block, ultrasound
      guided continuous TAP block provided similar analgesia in somatic pain and less
      analgesia in visceral pain. Moreover, the latter resulted in a lower incidence of
      postoperative urinary retention.

PMID- 28494893
TI  - Successful tracheal intubation with the McGRATHTM MAC during chest compression in
      a difficult airway patient.

PMID- 28494894
TI  - Dexamethasone for nerve blocks: Design matters!

PMID- 28494895
TI  - The efficacy of Labetalol versus Nitroglycerin for induction of controlled
      hypotension during sinus endoscopic surgery. A prospective, double-blind and
      randomized study.
AB  - OBJECTIVE: To assess the efficacy of labetalol versus nitroglycerin for induction
      of controlled hypotension during sinus endoscopic surgery. DESIGN: A prospective,
      double-blind and randomized study. SETTING: Carried out in operating room in
      university hospital. PATIENTS: 60 patients of both sexes, American Society of
      Anesthesiologists (ASA) physical status I and II, age range from 20 to 60years;
      scheduled for elective sinus endoscopic surgery under general anesthesia (GA).
      INTERVENTIONS: Patients were divided into two groups (30 each). NTG group
      received nitroglycerin infusion at a dose of 2-5MUg/kg/min, LAB group received
      labetalol infusion at a dose of 0.5-2mg/min. MEASUREMENTS: Surgical condition was
      assessed by surgeon using average category scale (ACS) of 0-5, a value of 2-3
      being ideal. In both groups mean arterial blood pressure (MAP) was gradually
      reduced till the ideal ACS for assessment of surgical condition, the target of
      ACS was 2-3 or lower. RESULTS: Both studied drugs achieved desired hypotension
      and improved visualization of surgical field by decreasing bleeding in the
      surgical site, but ideal surgical conditions were created at mild hypotension
      (MAP 70-75) in LAB group while same conditions were created at MAP of 65-69mmHg
      in NTG group. Mean heart rate (HR) was significantly higher in NTG group as
      compared to LAB group. Blood loss decreased significantly in LAB group.
      CONCLUSION: Both labetalol and NTG are effective and safe drugs for induction of
      controlled hypotension during sinus endoscopic surgery. While, labetalol was
      better as it offered optimum operative condition with mild decrease in blood
      pressure, decreased surgical bleeding and less tachycardia during the surgery.

PMID- 28494896
TI  - Occupational stress of anesthesia: Effects on aging.
AB  - BACKGROUND: Anesthesiology has been identified as a stressful specialty. Chronic
      psychological stress may lead to biological aging and skin aging. STUDY
      OBJECTIVE: The primary outcome was to measure physical health and emotional well
      being. Secondary outcomes include skin aging analysis, telomere shortening in
      anesthetists. DESIGN: This is a prospective observational study. SETTINGS:
      University of Alexandria. PATIENTS: Study was carried out on 366 ASA I-II
      physicians 30-50yr. INTERVENTIONS: Physicians were categorized into two equal
      groups, Group A (183) were anesthesia physicians and Group B (183) were
      physicians in less stressful specialties (laboratory specialties). Subgroup
      analysis was performed comparing 10years' intervals from (30-40) and from (40
      50). MEASUREMENTS: Physical health and emotional well-being were evaluated. All
      physicians were exposed to validated assessment scales for the upper face and the
      lower face for skin aging analysis. Blood sampling were drowned from all
      physicians during their working hours for analysis of telomere length, markers of
      oxidative stress. RESULTS: The two studied groups showed comparable demographic
      data and years of work. Physical health score and emotional health score showed
      higher values in Group A than Group B. Upper and lower face aesthetic unit
      summary score showed higher values in Group A than Group B. Telomere (TTAGGG)
      repeats for terminal restriction fragments (TRF) of Group A individuals revealed
      a significant decrease of TRF compared to Group B (p=0.001*). CONCLUSION:
      Biological and skin aging is evident in anesthetists who are chronically exposed
      to occupational stress, with obvious shorter telomere length, higher lower and
      upper face scores, and free radicals.

PMID- 28494897
TI  - Successful one-lung ventilation using a bronchial blocker tube for a large
      tracheal carcinoma resection.

PMID- 28494898
TI  - The effect of desflurane versus propofol anesthesia on postoperative delirium in
      elderly obese patients undergoing total knee replacement: A randomized,
      controlled, double-blinded clinical trial.
AB  - STUDY OBJECTIVE: The goal of this study was to investigate the incidence of
      delirium, wake-up times and early post-operative cognitive decline in one hundred
      obese elderly patients undergoing total knee arthroplasty. DESIGN: Prospective
      randomized trial. SETTINGS: Operating room, postoperative recovery area, hospital
      wards. PATIENTS: 100 obese patients (ASA II and III) undergoing primary total
      knee replacement under general anesthesia with a femoral nerve block catheter.
      INTERVENTION: Patients were prospectively randomized to maintenance anesthesia
      with either propofol or desflurane. MEASUREMENTS: The primary endpoint assessed
      by a blinded investigator was delirium as measured by the Confusion Assessment
      Method. Secondary endpoints were wake-up times and a battery of six different
      tests of cognitive function. MAIN RESULTS: Four of the 100 patients that gave
      informed consent withdrew from the study. Of the remaining 96 patients, 6
      patients did not complete full CAM testing. Preoperative pain scores, durations
      of surgery and anesthesia, and amount of intraoperative fentanyl were not
      different between groups. One patient in the propofol group developed delirium
      compared to zero in desflurane. One patient in desflurane group developed a
      confused state not characterized as delirium. Fifty percent of the patients
      exhibited a 20% decrease in the results of at least one cognitive test on the
      first 2days after surgery, with no difference between groups. There were no
      differences in the time to emergence from anesthesia, incidence of postoperative
      nausea and vomiting, and length of postanesthesia care unit (PACU) stay between
      the two groups. CONCLUSIONS: In conclusion we found a low incidence of delirium
      but significant cognitive decline in the first 48h after surgery. In this
      relatively small sample size of a hundred patients there was no difference in the
      incidence of postoperative delirium, early cognitive outcomes, or wake up times
      between the desflurane or propofol group.

PMID- 28494899
TI  - Perioperative management of patients with renal cell carcinoma with high level of
      IVC tumor thrombus invasion revisited.

PMID- 28494900
TI  - Perioperative strokes after coronary artery bypass grafting with staged carotid
      endarterectomy: A nationwide perspective.
AB  - STUDY OBJECTIVE: To examine the risk of perioperative stroke on in-hospital
      morbidity and mortality in staged coronary artery bypass grafting (CABG) and
      carotid endarterectomy (CEA) procedures. DESIGN: The National Inpatient Sample
      (NIS) database was used to extract data on all patients who underwent staged CABG
      CEA procedures. They were identified using the ICD-9 (International
      Classification of Diseases, Ninth Revision-Clinical Modification) diagnosis and
      procedure codes. SETTING: Multi-institutional. PATIENTS: Patients who underwent
      staged CABG and CEA from 1999 to 2011. INTERVENTIONS: Staged CABG and CEA
      procedures. MEASUREMENTS: Various pre-operative, and perioperative risk factors
      and their association with in-hospital mortality and morbidity were studied. MAIN
      RESULTS: The study cohort was grouped into 2761 patients who underwent staged CEA
      and CABG. The average age of the patient population was 69years. An in-hospital
      mortality of 4.96% (137) was observed. Staged procedures showed a morbidity rate
      of 69.21%. Patients with perioperative strokes had a mortality rate of 16.73%
      following staged procedures. Other notable risk factors for mortality and
      morbidity were post-operative myocardial infarction (MI) and congestive heart
      failure (CHF). CONCLUSION: Analysis of 2761 patients over a period of 12years
      (1999-2011) indicate perioperative stroke to be a strong post-operative
      predicator of in-hospital mortality and morbidity for staged procedures. Other
      significant factors such as advancing age, female gender and comorbidities like
      CHF, left ventricular dysfunction (LVD) and post-operative MI should also be
      considered when determining patient risk. Further investigative studies on staged
      CABG and CEA procedures are needed for better patient selection and for
      implementing preventative strategies such as neuroprotective medication and
      neuromonitoring to minimize the risk of ischemic strokes.

PMID- 28494901
TI  - A novel skin traction method to facilitate ultrasound-guided femoral nerve block
      in morbidly obese patients.

PMID- 28494902
TI  - Intraoperative anxiety and acute glaucoma: A possible link?

PMID- 28494903
TI  - Mom....Stop stressing me out!! Parental presence and its effect on cortisol
      levels in children.

PMID- 28494904
TI  - Complex regional pain syndrome type 1 predictors - Epidemiological perspective
      from a national database analysis.
AB  - OBJECTIVE: Complex regional pain syndrome type 1 is a disabling pain disorder
      with unclear etiology. It is usually triggered by an injury to a limb with or
      without specific nerve injury. The objective of this study is to explore the risk
      factors and predictors for this disease utilizing a large national database.
      DESIGN: Retrospective analysis of the Nationwide Inpatient Sample database from
      2007 to 2011 in the United States. SETTING AND PATIENTS: Adult inpatients
      diagnosed with complex regional pain syndrome type 1. STATISTICAL ANALYSIS: Chi
      square, simple and multivariate logistic regression analyses were conducted. The
      regression model was adjusted to the patient's demographics and comorbidities.
      MAIN RESULTS: There were 22,533 patients with the discharge diagnosis of complex
      regional pain syndrome type 1 of an inpatient sample of 33,406,123. It peaks
      between age 45 and 55. Female gender, Caucasian race, higher median household
      income, headache, depression, drug abuse and private insurance patients (vs
      Medicaid patients) were associated with higher rate of complex regional pain
      syndrome type 1. On the other hand, diabetes, obesity, hypothyroidism, and anemia
      were associated with a lower rate. CONCLUSIONS: Utilizing a large database, our
      study added more information to the risk profile of the complex regional pain
      syndrome type 1 in an inpatient population. Such information should be useful for
      physician for early recognition, diagnosis of patients at risk.

PMID- 28494905
TI  - Role of sugammadex in accelerating postoperative discharge: A meta-analysis.
AB  - STUDY OBJECTIVE: Sugammadex has been introduced for reversal of neuromuscular
      blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and
      safety have been established, data are conflicting as to whether it accelerates
      discharge to the surgical ward compared with neostigmine, which is traditionally
      used for reversing NMB. The object of this systematic review and meta-analysis
      was to review the research comparing sugammadex and neostigmine in the context of
      patient discharge after general anesthesia. DESIGN: Systematic review and meta
      analysis. SETTING: University medical hospital. PATIENTS: Five-hundred eighteen
      patients from six studies were included. METHODS: A comprehensive search was
      conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library
      electronic databases to identify randomized controlled trials written in English.
      Two reviewers independently selected the studies, extracted data regarding
      postoperative discharge, and assessed the trials' methodological quality and
      evidence level. Postoperative discharge time was determined from the operating
      room (OR) to the postanesthesia care unit (PACU) and from the PACU to the
      surgical ward. This study was conducted using PRISMA methodology. MEASUREMENTS:
      Time to discharge after NMB reversal with sugammadex or neostigmine. MAIN
      RESULTS: Compared with neostigmine, sugammadex was associated with a
      significantly faster discharge from the OR to the PACU (mean difference
      [MD]=22.14min, 95% CI (14.62, 29.67), P<0.0001, I2=0%) and from the PACU to the
      surgical ward (MD=16.95min, 95% CI (0.23, 33.67), P=0.0469, I2=98.4%). Similarly,
      discharge-readiness was shorter for sugammadex than for neostigmine from the OR
      to the PACU (MD=5.58min, 95% CI (3.03, 8.14), P<=0.0001, I2=0%). However,
      discharge-readiness was similar in both groups for patients moving from the PACU
      to the surgical ward (MD=-1.10min, 95% CI (-5.69, 3.50), P=0.6394, I2=25.3%).
      CONCLUSIONS: Results from this meta-analysis suggest that sugammadex accelerates
      postoperative discharge of patients after general anesthesia compared with
      neostigmine.

PMID- 28494906
TI  - The effect of morphine added to bupivacaine in ultrasound guided transversus
      abdominis plane (TAP) block for postoperative analgesia following lower abdominal
      cancer surgery, a randomized controlled study.
AB  - OBJECTIVES: Transversus abdominis plane (TAP) block used for management of
      surgical abdominal pain by injecting local anesthetics into the plane between the
      internal oblique and transversus abdominis muscles. We aimed to explore the
      effect of adding morphine to bupivacaine in ultrasound guided TAP-block in
      patients undergoing lower abdominal cancer surgery. STUDY DESIGN: Randomized,
      double-blind, prospective study. Clinical trial identifier: NCT02566096. SETTING:
      Academic medical center. PATIENTS: Sixty patients were enrolled in this study
      after ethical committee approval. INTERVENTIONS: Patients divided into 2 groups
      (30 each): Bupivacaine group (GB): given ultrasound guided TAP-block 20ml 0.5%
      bupivacaine diluted in 20ml saline; Morphine group (GM): given ultrasound guided
      TAP-block with 20ml 0.5% bupivacaine+10mg morphine sulphate diluted in 20ml
      saline. MEASUREMENTS: Patients were observed for total morphine consumption, time
      for first request of rescue analgesia, sedation scores, hemodynamics and side
      effects for 24h postoperatively. RESULTS: Morphine added to bupivacaine in TAP
      block compared to bupivacaine alone reduced total morphine consumption (5.33+/
      1.28mg) (10.70+/-3.09mg) respectively (p<0.001), prolonged the time to first
      request of analgesia (10.40+/-4.96h) (6.97+/-3.26h) respectively (p<0.008), with
      a statistically significant decrease in (VAS-M) in GM compared with GB at 12h
      postoperatively (p<0.002). No significant differences in hemodynamics,
      respiratory rate, oxygen saturation, sedation score, and side effects except for
      nausea were observed (p>0.05). CONCLUSION: Addition of morphine to bupivacaine in
      TAP block is effective method for pain management in patients undergoing major
      abdominal cancer surgery without serious side effects.

PMID- 28494907
TI  - Internet-delivered, preoperative, preparation program (I-PPP): Development and
      examination of effectiveness.
AB  - STUDY OBJECTIVE: Limited evidence-based, interactive, Internet-delivered
      preoperative preparation programs for children and their parents exist. The
      purpose of this investigation was to develop and examine the effectiveness of the
      Internet-delivered, preoperative program (I-PPP) in alleviating prepoperative
      anxiety in children undergoing outpatient surgery. In Study 1, the I-PPP was
      developed and then evaluated by parent/child dyads and health care professionals.
      In Study 2, the effectiveness of I-PPP was examined. DESIGN: This study was a
      development and effectiveness study. SETTING: For Study 1, participants were
      recruited from the community. For Study 2, participants were recruited from the
      Royal University Hospital. PATIENTS: In Study 1, participants were 9 parent/child
      dyads and 5 health care professionals. In Study 2, participants were 32 children
      (3-7years) scheduled for outpatient surgery and one parent for each child.
      INTERVENTION: In Study 1, I-PPP modules were created and parent/child dyads and
      health care professionals evaluated I-PPP modules and treatment credibility. In
      Study 2, child patients and their parents completed the I-PPP prior to day of
      surgery. MEASUREMENTS: Observer-rated anxiety of child participants was measured
      during the day surgery experience. Parent state anxiety was measured prior to
      completing I-PPP, pre- and post-surgery. Post-surgery parents provided comments
      regarding the I-PPP. Post-surgery child behaviour change was assessed. MAIN
      RESULTS: For Study 1, ratings for I-PPP components and treatment credibility
      surpassed our acceptability criterion. Minor changes were made to I-PPP. For
      Study 2, mYPAS scores were stable across day surgery. mYPAS scores in current
      study at induction did not differ significantly from benchmark studies.
      Significant reduction in parent anxiety was observed pre- to post-surgery.
      Parents positively endorsed the program. Negative post-operative behaviours were
      observed in a proportion of children. CONCLUSIONS: Our findings suggest that I
      PPP represents a viable option for preoperative preparation for children and
      their parents.

PMID- 28494908
TI  - For assessment of changes in intraoperative red blood cell transfusion practices
      over time, the pooled incidence of transfusion correlates highly with total units
      transfused.
AB  - STUDY OBJECTIVE: Multiple studies nationwide and at single hospitals have
      examined changes over time in the incidence of perioperative red blood cell (RBC)
      transfusion. However, the cost of RBC transfusions is related to the number of
      RBC units transfused, not to the incidence. We evaluate whether the readily
      available incidence of RBC transfusion can be used as a valid surrogate measure.
      DESIGN: Observational retrospective study. SETTING: One tertiary, academic
      hospital. PATIENTS: 394,789 cases of 1885 procedures over N=42 quarters of the
      year. INTERVENTIONS: None. MEASUREMENT: Incidence and number of RBC units
      transfused intraoperatively. MAIN RESULTS: The number of RBC units transfused per
      case did not follow a Poisson distribution, confirming that the number of units
      and incidence of transfusion are not interchangeable for analyzing decisions by
      case. However, with all cases of each quarter combined, the Spearman correlation
      was 0.98+/-0.01 between each quarter's incidence of RBC transfusion and mean RBC
      units transfused per case (P<0.0001). CONCLUSIONS: For assessment of changes in
      intraoperative RBC transfusion practices over years, it is sufficient to analyze
      the pooled incidence of transfusion, rather than to calculate the number of units
      transfused.

PMID- 28494909
TI  - Remifentanil as an alternative to epidural analgesia for vaginal delivery: A meta
      analysis of randomized trials.
AB  - OBJECTIVES: Although epidural analgesia is considered the gold standard for labor
      pain management, its use may be restricted in some conditions due to clinical
      contraindications or availability, and suitable alternatives may be required. The
      objective of this meta-analysis was to determine whether evidence from randomized
      trials suggests remifentanil PCA (R-PCA) results in significant differences in
      maternal satisfaction, analgesic efficacy, and safety compared with conventional
      epidural analgesia (EA). DESIGN: We conducted a meta-analysis after
      systematically searching MEDLINE, EMBASE and Cochrane Library for all randomized
      controlled trials (RCTs) allocating parturients to R-PCA or EA and reporting at
      least one outcome of interest. PATIENTS: Eight randomized trials of R-PCA vs EA
      with 2351 patients were included. MEASUREMENTS: The primary outcome of interest
      was maternal satisfaction. Secondary outcomes included visual analog pain score
      (VAS at 1, 2, 3h postoperatively), nausea, vomiting, pruritus, hypoxemia, acute
      respiratory depression or death (maternal or neonatal), need for Cesarean
      section, and neonatal Apgar score. MAIN RESULTS: Meta-analysis of the randomized
      trials showed no significant differences between the R-PCA and EA groups for
      maternal satisfaction, VAS at 2 or 3h, nausea, vomiting, need for cesarean
      section, respiratory depression, umbilical pH, and neonatal Apgar score at 1min
      and 5min. However, incidence of hypoxemia was higher [OR 7.48, 95%CI 3.42-16.36]
      and VAS at 1h was slightly higher [WMD 1.33, 95%CI 0.30-2.36] with R-PCA versus
      EA. Pruritus was less frequent in the R-PCA group [OR 0.54, 95%CI 0.32-0.89].
      Acute respiratory failure and death were not reported in any of the studies.
      CONCLUSIONS: While no significant differences were detected for maternal
      satisfaction or for most clinical outcomes, this meta-analysis remains
      underpowered to rule out clinically-important differences due to the few existing
      randomized trials. For obstetric patients who are not candidates for EA, R-PCA
      may provide an alternative for analgesia in the peri-partum period, but caution
      is warranted particularly regarding hypoxemia, and suggests the need for
      increased surveillance and monitoring for R-PCA. Further adequately powered
      randomized trials with a focus on clinically-relevant maternal and neonatal
      outcomes are required to more accurately characterize the relative benefits and
      risks of R-PCA versus EA in this population.

PMID- 28494910
TI  - The effects of maternal presence during anesthesia induction on salivary cortisol
      levels in children undergoing tonsillectomy and/or adenoidectomy.
AB  - OBJECTIVE: Although parental presence during anesthesia induction is suggested to
      diminish operative stress level in children, there have been conflicting results
      about this strategy. The aim of this study was to evaluate the effects of
      maternal presence during induction on operative stress level in children who had
      tonsillectomy and/or adenoidectomy by determining the salivary cortisol levels.
      DESIGN: Non-randomized clinical study. SETTING: Preoperative and postoperative
      recovery rooms, operating room. PATIENTS: The study included 48 children between
      the ages of 5-12years who underwent tonsillectomy and/or adenoidectomy.
      INTERVENTIONS: The patients were divided into 2 groups. The children in group 1
      were separated from their mothers at the preparation room. The children in group
      2 stayed together with their mothers till the anesthesia induction. MEASUREMENTS:
      State Trait Anxiety Inventory (STAI) was performed to the mothers and children
      preoperatively. Salivary cortisol levels were evaluated in 4 different time
      frames: 1) in preparation room, 2) after anesthesia induction, 3) at the 30th
      minute of operation, and 4) in postoperative recovery room. MAIN RESULTS: There
      were no statistically significant differences between groups regarding
      demographic features, and operation or anesthesia times. The child's or mothers'
      preoperative anxiety scores were not different between the groups. Salivary
      cortisol levels in group 1 were significantly increased after induction and in
      recovery room compared to those in group 2 (p: 0.001, and p: 0.02, respectively).
      CONCLUSIONS: We have determined decreased salivary cortisol levels during
      anesthesia induction and recovery in the maternal presence revealing diminished
      stress in these periods. Further studies are warranted to determine the effects
      of parental presence during anesthesia induction especially on surgical outcomes.

PMID- 28494912
TI  - ASA physical status classification system: Is it consistent amongst providers and
      useful in determining need for pre-operative evaluation resources?

PMID- 28494911
TI  - Levosimendan does not provide mortality benefit over dobutamine in adult patients
      with septic shock: A meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: Despite of advancement in intensive care medicine, sepsis and septic
      shock carry a high mortality. Levosimendan, an inodilator, may be promising for
      septic shock patients with myocardial dysfunction; however, firm evidence is
      lacking. In this meta- analysis of randomized controlled trials, levosimendan has
      been compared with dobutamine in adult patients with sepsis and septic shock.
      DESIGN: Meta-analysis of randomized controlled trial. SETTING: Intensive-care
      unit. PARTICIPANTS: Adult septic shock patients. INTERVENTION: Adult septic shock
      patients received dobutamine or levosimendan. MAIN OUTCOME MEASURE: Mortality at
      longest follow-up, blood lactate level, cardiac index and noradrenaline
      requirement. RESULTS: Data from 7 randomized trials have been included in this
      meta-analysis. Levosimendan has no benefit in terms of mortality at longest
      follow up in comparison to dobutamine (Odds ratio 0.77, 95% CI 0.45, 132; p=0.34)
      and length of ICU stay (MD -4.7days, 95% CI -10.3, 0.9days, p=0.10). Patients
      received levosimendan had less blood lactate level (standardized mean difference 
      0.95; 95% CI -1.64, -0.27; p=0.006) and higher cardiac index (mean difference
      0.44; 95% CI 0.17, 0.71; p=0.001). Noradrenaline requirements are similar in both
      the groups. CONCLUSION: There is no evidence that levosimendan is superior to
      dobutamine in adult patients with sepsis and septic shock. Further large
      randomized trials are necessary in this area.

PMID- 28494913
TI  - Epidural catheter cutting: mechanisms and management.

PMID- 28494914
TI  - The effect of melatonin on early postoperative cognitive decline in elderly
      patients undergoing hip arthroplasty: A randomized controlled trial.
AB  - STUDY OBJECTIVE: The purpose of the present study was to investigate whether
      exogenous melatonin supplementation could ameliorate early postoperative
      cognitive decline (POCD) in aged patients undergoing hip arthroplasty with spinal
      anesthesia. DESIGN: Prospective cohort study. SETTING: Department of
      Anesthesiology, Jinling Hospital, Nanjing University, Nanjing, China. PATIENTS:
      One hundred and thirty-nine patients with ASA I-III, older than 65yr of age (mean
      age: 74.5+/-5.5; gender: male 53 and female 86), scheduled for hip arthroplasty
      were included in the present study. INTERVENTIONS: Patients were randomized to
      receive 1mg oral melatonin or placebo daily 1h before bedtime one day before
      surgery and for another 5 consecutive days postoperatively. MEASUREMENTS: The
      subject assessment, including Mini-Mental State Examination (MMSE) score,
      subjective sleep quality, general well-being, postoperative fatigue, and visual
      analogue scale for pain were evaluated pre-operatively and at days 1, 3, 5, and 7
      after surgery. MAIN RESULTS: The MMSE score in the control group decreased
      significantly after surgery when compared with its own preoperative value or the
      melatonin group at days 1, 3, and 5. However, the MMSE score in the melatonin
      group remained unchanged during the 7days of monitoring. In addition, significant
      postoperative impairments of subjective sleep quality, general well-being, and
      fatigue were found in the control group when compared with the melatonin group.
      CONCLUSION: Peroperative melatonin supplementation might improve early POCD,
      suggesting restoration of normal circadian function with good sleep quality may
      be one of the key factors in preventing or treating POCD.

PMID- 28494915
TI  - Injection speed of spinal anaesthesia for Caesarean delivery in Asian women and
      the incidence of hypotension: A randomised controlled trial.
AB  - STUDY OBJECTIVE: The purpose of this investigation was to determine if a slower
      speed of spinal anaesthesia injection would reduce the incidence of hypotension.
      STUDY DESIGN: Randomised controlled trial. SETTING: Tertiary level hospital in
      Malaysia. PATIENTS: 77 patients undergoing elective Caesarean delivery.
      INTERVENTION: Differing speeds of spinal injection. MEASUREMENTS: Systolic blood
      pressure was assessed every minute for the first 10min and incidence of
      hypotension (reduction in blood pressure of >30% of baseline) was recorded. The
      use of vasopressor and occurrence of nausea/vomiting were also recorded. MAIN
      RESULTS: 36 patients in SLOW group and 41 patients in FAST group were recruited
      into the study. There was no significant difference in blood pressure drop of
      >30% (p=0.497) between the two groups. There was no difference in the amount of
      vasopressor used and incidence of nausea/vomiting in both groups. CONCLUSION: In
      our study population, there was no difference in incidence of hypotension and
      nausea/vomiting when spinal injection time is prolonged beyond 15s to 60s. TRIAL
      REGISTRATION: ClinicalTrials.govNCT02275897. Registered on 15 October 2014.

PMID- 28494916
TI  - Best practices for our most delicate patients.

PMID- 28494918
TI  - Do we need another short-acting beta-blocker? A definite maybe....

PMID- 28494917
TI  - Validation of the Nexfin(r) non-invasive continuous blood pressure monitoring
      validated against Riva-Rocci/Korotkoff in a bariatric patient population.
AB  - STUDY OBJECTIVE: The present study aimed to validate the Nexfin(r) monitor and to
      assess the accuracy compared to classical sphygmomanometry (Riva-Rocci/Korotkoff
      (RRK)) blood pressure (BP) measurements in patients with obesity scheduled for
      bariatric surgery. DESIGN: Validation study. SETTING: Outpatient clinic for
      bariatric surgery. PATIENTS: 33 patients scheduled for bariatric surgery.
      MEASUREMENTS: The validation process was done according to the protocols
      developed by the European Society of Hypertension from 2010. The Nexfin(r)
      monitor (Edwards Lifesciences/BMEYE B.V., Amsterdam, The Netherlands) calculates
      beat-to-beat blood pressure from finger pulse wave analysis. Measurements of
      systolic and diastolic BP were obtained using classical sphygmomanometry and the
      Nexfin(r) alternatingly. MAIN RESULTS: In total 99 pairs of BP measurements were
      used. The device failed pass phase 1 as 65 systolic readings fell within 5mmHg
      (73 required). And 61, 76 and 90 diastolic readings fell within 5, 10 and 15mmHg
      respectively. Finally, it failed to pass phase 2 as 23 patients for systolic and
      25 for diastolic had at least 2/3 of their comparisons falling within 5mmHg (24
      required) but 10 subjects for systolic and 8 for diastolic had all three
      comparisons more than 5mmHg different from the RRK readings (zero allowed). Mean
      differences were 7.8+/-6.9mmHg for SBP and 8.0+/-7.2mmHg for DBP. CONCLUSION:
      Using the revised protocol, the Nexfin(r) device was not able to pass validation.
      However using the original protocol, the Nexfin(r) device passed phase 1 and 2.1
      of the validation process and failed to pass phase 2.2.

PMID- 28494919
TI  - Multimodal therapy facilitates a fast-track recovery after surgery - are
      potential drug-drug interactions of clinical significance in the perioperative
      period?

PMID- 28494921
TI  - Proliferative diabetic retinopathy: laser or eye injection?

PMID- 28494920
TI  - Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation
      for best corrected visual acuity in patients with proliferative diabetic
      retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised,
      controlled, phase 2b, non-inferiority trial.
AB  - BACKGROUND: Proliferative diabetic retinopathy is the most common cause of severe
      sight impairment in people with diabetes. Proliferative diabetic retinopathy has
      been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We
      report the 1 year safety and efficacy of intravitreal aflibercept. METHODS: In
      this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged >=18
      years) with type 1 or 2 diabetes and previously untreated or post-laser treated
      active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic
      centres. Patients were randomly assigned (1:1) to repeated intravitreal
      aflibercept (2 mg/0.05 mL at baseline, 4 weeks, and 8 weeks, and from week 12
      patients were reviewed every 4 weeks and aflibercept injections were given as
      needed) or PRP standard care (single spot or mutlispot laser at baseline,
      fractionated fortnightly thereafter, and from week 12 patients were assessed
      every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by
      minimisation with a web-based computer generated system. Primary outcome
      assessors were masked optometrists. The treating ophthalmologists and
      participants were not masked. The primary outcome was defined as a change in best
      corrected visual acuity at 52 weeks with a linear mixed-effect model that
      estimated adjusted treatment effects at both 12 weeks and 52 weeks, having
      excluded fluctuations in best corrected visual acuity owing to vitreous
      haemorrhage. This modified intention-to-treat analysis was reapplied to the per
      protocol participants. The non-inferiority margin was prespecified as -5 Early
      Treatment Diabetic Retinopathy Study letters. Safety was assessed in all
      participants. This trial is registered with ISRCTN registry, number 32207582.
      FINDINGS: We recruited 232 participants (116 per group) between Aug 22, 2014 and
      Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group)
      contributed to the modified intention-to-treat model, and 210 participants (104
      in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was
      non-inferior and superior to PRP in both the modified intention-to-treat
      population (mean best corrected visual acuity difference 3.9 letters [95% CI 2.3
      5.6], p<0.0001) and the per-protocol population (4.0 letters [2.4-5.7],
      p<0.0001). There were no safety concerns. The 95% CI adjusted difference between
      groups was more than the prespecified acceptable margin of -5 letters at both 12
      weeks and 52 weeks. INTERPRETATION: Patients with proliferative diabetic
      retinopathy who were treated with intravitreal aflibercept had an improved
      outcome at 1 year compared with those treated with PRP standard care. FUNDING:
      The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and
      National Institute for Health Research partnership.

PMID- 28494922
TI  - Analysis of JAK-STAT signaling pathway genes and their microRNAs in the
      intestinal mucosa of genetically disparate chicken lines induced with necrotic
      enteritis.
AB  - The JAK-STAT signaling pathway plays a key role in cytokine and growth factor
      activation and is involved in several cellular functions and diseases. The main
      objective of this study was to investigate the expression of candidate JAK-STAT
      pathway genes and their regulators and interactors in the intestinal mucosal
      layer of two genetically disparate chicken lines [Marek's disease (MD)-resistant
      line 6.3 and MD-susceptible line 7.2] induced with necrotic enteritis (NE).
      Through RNA-sequencing, we investigated 116 JAK-STAT signaling pathway-related
      genes that were significant and differentially expressed between the intestinal
      mucosa of the two lines compared with respective uninfected controls. About 15
      JAK-STAT pathway genes were further verified by qRT-PCR, and the results were in
      agreement with our sequencing data. All the identified 116 genes were annotated
      through Gene Ontology and mapped to the KEGG chicken JAK-STAT signaling pathway.
      To the best of our knowledge, this is the first study to represent the
      transcriptional analysis of a large number of candidate genes, regulators, and
      potential interactors in the JAK-STAT pathway of the two chicken lines induced
      with NE. Several key genes of the interactome, namely, STAT1/3/4, STAT5B, JAK1-3,
      TYK2, AKT1/3, SOCS1-5, PIAS1/2/4, PTPN6/11, and PIK3, were determined to be
      differentially expressed in the two lines. Moreover, we detected 68 known miRNAs
      variably targeting JAK-STAT pathway genes and differentially expressed in the two
      lines induced with NE. The RNA-sequencing and bioinformatics analyses in this
      study provided an abundance of data that will be useful for future studies on JAK
      STAT pathways associated with the functions of two genetically disparate chicken
      lines induced with NE.

PMID- 28494923
TI  - Effects of serum amyloid A on matrix metalloproteinase-9 production in feline
      lymphoma-derived cell lines.
AB  - Serum amyloid A (SAA) concentration and plasma matrix metalloproteinase-9 (MMP-9)
      levels are increased in cats with lymphoma. In the present study, the association
      between SAA and MMP-9 production was evaluated using recombinant feline SAA
      (rfSAA) and three feline lymphoma-derived cell lines: 3201, MS4, and MCC. MMP-9
      mRNA expression was significantly increased by rfSAA stimulation only in MCC
      cells. Secreted MMP-9 protein in culture media was confirmed by gelatin
      zymography, with clear bands of MMP-9 detected in MCC cells following rfSAA
      stimulation. A significant increase in semi-quantified MMP-9 levels was observed
      with 5 and 25MUg/ml of rfSAA stimulation. The infiltrative activities of feline
      lymphoma cells, assessed by the matrigel transwell assay, showed that rfSAA
      stimulated cell infiltration in MCC cells, in addition to MMP-9 expression.
      Although the response to rfSAA stimulation varied between cell lines, the results
      showed that rfSAA can stimulate MMP-9 production and infiltration of feline
      lymphoma-derived cells. The findings of this study have identified a novel role
      for SAA in the progression of some forms of feline lymphoma.

PMID- 28494924
TI  - Loss of CD45 cell surface expression in canine T-zone lymphoma results from
      reduced gene expression.
AB  - Canine T-zone lymphoma (TZL) is a peculiar lymphoma subtype characterized by an
      indolent clinical course and aberrant CD45-negative phenotype, commonly
      recognized by flow cytometry (FC). Recent studies have described clinical
      presentation and behavior, but to date the mechanisms behind the loss of CD45
      protein expression have never been investigated. The aims of this study were: 1)
      to confirm the absence of CD45 in canine TZL via the concomitant use of FC and
      immunohistochemistry with two different sources of antibody; and 2) to
      investigate the amount of CD45 transcript and the presence of CD45 gene in the
      neoplastic cells of dogs affected by TZL. 57 lymph node aspirates were included
      in the present study: 40 (70.2%) TZLs, 7 (12.3%) high grade T-cell lymphomas and
      10 (17.5%) reactive lymph nodes. Neoplastic cells and normal T-cells were
      isolated from TZL and reactive lymph nodes, respectively, via cell sorting.
      Immunohistochemistry was performed on 2 TZL, 2 reactive lymph nodes and 2
      Peripheral T-cell Lymphomas. Total RNA and genomic DNA were extracted from lymph
      nodes aspirates. Two different quantitative real-time PCR experiments were
      designed, to determine the amount of the CD45 transcript and of the corresponding
      gene fragment. All TZL cases were negative for CD45 at immunohistochemistry. CD45
      transcript amount was significantly lower in TZL compared to controls (p<0.001).
      This difference was not significant (p=0.584) for CD45 DNA load, that was similar
      between TZL and controls. Moreover, CD45 transcript amount was inversely
      correlated with the percentage of neoplastic cells in each TZL sample (p=0.010).
      These results confirm that CD45 protein is lacking on cell surface irrespective
      of the technique and antibody source adopted. This phenotypic aberrancy is
      apparently due to the absence of gene transcription, as CD45 DNA was present,
      whereas CD45 transcript was virtually absent in the neoplastic cells. The data
      here reported support further studies investigating possible factors impairing
      CD45 gene transcription.

PMID- 28494925
TI  - Comparison of humoral and T-cell-mediated immune responses to a single dose of
      Bovela(r) live double deleted BVDV vaccine or to a field BVDV strain.
AB  - The objective of this study was to determine and compare the humoral and cellular
      immune responses of calves exposed to a single dose of Bovela(r) bovine viral
      diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV)
      of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old
      Holstein steer calves that tested negative for persistent BVDV by ear notch
      immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves
      were screened by multi-parameter flow cytometry (MP-FCM) 1 week before
      vaccination to ensure that they were negative for T cell responses to the BVDV
      types 1 and 2 viruses in the Bovela(r) vaccine. Calves were assigned to 3
      treatment groups: control (PBS), FSV inoculated, and Bovela(r) vaccinated. The
      humoral response was tested by standard serum virus neutralization (SVN) test to
      BVDV types 1 (Singer strain) and 2 (strain 125). The response by CD4, CD8, and
      gamma delta (gammadelta TCR) T cells was evaluated by MP-FCM using individual
      BVDV types 1 and 2 from Bovela(r) vaccine as recall antigens at 5, 6, and 7 weeks
      after vaccination. Activation markers used were upregulation of surface CD25 (IL
      2R), intracellular interferon gamma (IFNgamma) and intracellular interleukin 4
      (IL-4). Each T cell subset was evaluated for increased expression of each
      activation marker compared to non-antigen stimulated cells of the same animal.
      All Bovela(r) vaccinated and FSV inoculated calves produced SVN antibodies to
      both BVDV types 1 and 2 while control animals remained seronegative throughout
      the study. The mean (weeks 5, 6, and 7) T cell recall responses to Bovela(r) BVDV
      type 1 and type 2 recall antigens were numerically higher in all three T cell
      subsets (CD4, CD8, and gammadelta TCR) for all three activation markers (CD25,
      IFNgamma, and IL-4) when compared to either the control animals or to the FSV
      inoculated animals. These differences were often, but not always, statistically
      significant (P<0.05).

PMID- 28494926
TI  - Gastrokine mRNA expression in gastric tissue from dogs with helicobacter
      colonisation but without inflammatory change during treatment.
AB  - Gastrokines (GKNs) are bioactive substances secreted by gastric cells. Evidence
      supports functional roles for GKNs in gastric homeostasis, immune responses and
      tumour suppression. Down-regulation has been reported in Helicobacter pylori
      associated gastritis and other inflammatory gastrointestinal conditions in mice
      and people. The aim of this study was to evaluate GKN gene expression in dogs
      positive for other Helicobacter spp. both before and after treatment. Expression
      of Gkn-1 and Gkn-2 mRNA was studied in endoscopic biopsy samples collected from
      seven healthy dogs over three time-points pre- (T0) and at 1 and 18 weeks post
      treatment for Helicobacter spp. colonisation (T1 & T2). The relative expression
      software tool (REST) was used to provide efficiency corrected expression ratios
      for comparisons between groups and these results were compared to a standard
      2DeltaDeltaCT methodology. Compared with T1 Gkn1 and Gkn2 mRNA expression was
      greater at T0 by a mean factor of 2.53 (SE=1.83-3.54) for Gkn1 (P=0.000) and 2.85
      (SE=2.23-3.75) for Gkn2 (P=0.000). This difference was attenuated when
      comparisons were made between T0 and T2. Histopathological evidence of gastritis
      was not present in any Helicobacter spp. positive sample. When compared to post
      eradication samples Gkn gene expression is increased in the presence of
      Helicobacter spp. in dogs without evidence for concurrent inflammation. Further
      evaluation is required to determine the relevance of this finding, however given
      a suspected role in gastric homeostasis, up-regulation of GKN1 and GKN2 could
      limit development of gastritis in Helicobacter spp. positive dogs.

PMID- 28494927
TI  - Comparison of interferon and bovine herpesvirus-1-specific IgA levels in nasal
      secretions of dairy cattle administered an intranasal modified live viral vaccine
      prior to calving or on the day of calving.
AB  - Thirty-two Holstein cows were allocated to receive intranasal vaccination with
      modified live bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus
      (BRSV) and parainfluenza type 3 virus (PI3V) vaccine either two weeks prior to
      their projected calving date, or within 24h after calving. Nasal secretions were
      collected twice at a 12-h interval on the day prior to vaccination (day 0) and at
      2, 4, 7, 10 and 14days post vaccination to measure interferon (IFN) alpha, IFN
      beta, IFN-gamma, and BHV-1-specific IgA by ELISA. Serum neutralizing antibody
      titers to BHV-1 and BRSV were measured on days 0, 7, and 14. There was a
      significant treatment effect (p<0.0004) and interaction (p<0.05) on nasal BHV-1
      IgA levels, with higher IgA levels in cows vaccinated within 24h after calving.
      There was a significant treatment effect on nasal IFN-gamma concentration
      (p<0.05) and on nasal total IFN concentration (p<0.05), with higher IFN-gamma and
      total IFN concentrations seen in cows vaccinated within 24h after calving. There
      was no significant treatment or interaction effect on nasal IFN-alpha or IFN-beta
      concentrations, or on serum neutralizing titers to BRSV. In spite of prior viral
      vaccination during the previous lactation, cows vaccinated on the day of calving
      responded to an intranasal viral vaccination with increased concentrations of IFN
      gamma and increased titers of IgA following vaccination which was significantly
      higher than cows vaccinated precalving. This study is the first to examine
      respiratory mucosal responses in immunologically mature dairy cattle vaccinated
      intranasally before and after calving.

PMID- 28494928
TI  - Shotgun proteomic analysis of the secretome of bovine endometrial mesenchymal
      progenitor/stem cells challenged or not with bacterial lipopolysaccharide.
AB  - The use of the conditioned medium (CM) for diseases treatment is based on its
      enrichment with biomolecules with therapeutic properties and themselves have a
      beneficial effect. Secretome of bovine endometrial mesenchymal progenitor/stem
      cells (eMSCs) using a proteomics approach is until now unknown. This work aimed
      to evaluate the secretome of bovine eMSCs-CM challenged or not with
      lipopolysaccharide (LPS). For this, eMSCs characterized were challenged (TG) or
      not (CG). The CM was collected 12h after stimulation and submitted to mass
      spectrometry analysis. The classification of identified proteins was done by
      PANTHER according to biological processes, molecular function, cellular component
      and protein class. 397 protein groups were identified in TG and 302 in CG. We
      observed positive enrichment for antibacterial response proteins, macrophage
      activation function, receptor-mediated endocytosis, hydrolase activity,
      inhibitory enzyme in TG, and for activity structural molecule and intermediate
      filament cytoskeleton in the CG. Our experimental model shows that eMSCs respond
      to LPS in the concentration used and can be used to study immune-inflammatory
      response, besides of the secretion of proteins mainly related to tissue
      remodeling, immune response and angiogenesis which is an interesting feature for
      use in cell therapy.

PMID- 28494929
TI  - Investigation of corneal autoantibodies in horses with immune mediated keratitis
      (IMMK).
AB  - Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in
      horses causing intermittent ocular pain, eventually resulting in visual
      impairment. Affected horses typically respond to immunomodulatory treatment.
      However, the underlying cause of the disease remains enigmatic. The current study
      was undertaken to investigate the presence of autoantibodies in horses with
      immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls
      screening for serum autoantibodies against the corneal proteome using indirect
      immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis
      (2DE) with subsequent western blot analysis was performed followed by mass
      spectrometric identification of bands or spots of interest. Indirect
      immunofluorescence did not reveal a difference in immune response towards corneal
      proteins between healthy horses and those with IMMK. Using western blot analysis
      some horses affected by IMMK (4/28) showed a single band (1D) or a single spot
      (2DE) (5/28) not detected in healthy controls. The corresponding spot was
      identified as maspin (SERPINB5), a protein responsible for the inhibition of
      corneal vascularisation, cell migration and cell adhesion to the extracellular
      matrix. Tests with a recombinant human protein commercially available did not
      verify blot findings, but the human protein may not be fully cross-reactive.
      Still, maspin might play a role in some cases of equine IMMK. Further research is
      needed to clarify the etiology of this disease.

PMID- 28494931
TI  - Hemophagocytic lymphohistiocytosis in acute African swine fever clinic.
AB  - INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) usually has been defined
      as the combination of a proliferation of cytologically benign, actively
      phagocytic macrophages in bone marrow, spleen, lymph nodes, etc. in association
      with fever, cytopenia, splenomegaly, and hypertriglyceridemia. HLH is often
      triggered by viral infection. The aim of this study was to ascertain the features
      of HLH involvement in African swine fever virus (ASFV) (genotype II)
      pathogenesis. METHODS: The serum levels of macrophage colony-stimulating factor
      (MCSF) and granulocyte-macrophage colony-stimulating factor (GMCSF), as well as
      the histological constitution (for hemophagocytic macrophages detection) of
      various organs of pigs infected with ASFV genotype II were investigated. The
      diagnosis of HLH was made according to universally accepted human criteria.
      RESULTS: The association of fever, cytopenias, splenomegaly, and hemophagocytosis
      was present in 87.5% of the infected pigs (absence of hyperthermia in one of
      eight pigs). Marked hypertriglyceridemia was observed at 3-4days post infection.
      Previously it was shown that ASFV induced a significant decrease in the level of
      fibrinogen from day 5 till the end of experiment. Progression of the HLH
      coincided with a temporary increase in the serum levels of MCSF levels (early
      stage of disease) and GMCSF levels (2-3 pays post infection). CONCLUSIONS:
      Hemophagocytic syndrome should be suspected in ASFV (genotypeII) infected pigs.

PMID- 28494930
TI  - A ROS-dependent and Caspase-3-mediated apoptosis in sheep bronchial epithelial
      cells in response to Mycoplasma Ovipneumoniae infections.
AB  - Mycoplasma Ovipneumoniae (M. ovipneumoniae) is a primary etiological agent of
      enzootic pneumonia in sheep and goats. It can enter and colonize ovine
      respiratory epithelial cells to establish an infection, which leads a serious
      cell death of epithelial cells. However, the nature of the interaction between
      pathogen of M. ovipneumoniae and host cells in the cell injury is currently not
      well understood. In this study, we investigated the epithelial cell apoptosis
      caused by an infection of M. ovipneumoniae in sheep primary air-liquid interface
      (ALI) epithelial cultures. The results showed that M. ovipneumoniae could
      specifically bind to ciliated cells at early stage of infection. Flow cytometric
      analysis demonstrated that an infection of M. ovipneumoniae induced a time
      dependent cell apoptotic cell death, accompanied with an increased production of
      extracellular nitric oxide (NO), intracellular reactive oxygen species (ROS)
      production and activation of caspase-3 signaling in sheep bronchial epithelial
      cells. The induced cell apoptosis was further confirmed by a transferase-mediated
      deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay. Interestingly,
      the M. ovipneumoniae-induced apoptosis and activation of caspase-3 were
      correlated with the production of ROS but not NO. Mechanistically, M.
      ovipneumoniae-induced cell apoptosis was mediated by a mechanism by increasing
      the expression of phosphorylation of p38 and pro-apoptotic proteins, and
      activating caspase-3, caspase-8 and poly ADP-ribose polymerase (PARP) cleavage.
      These results suggest a ROS-dependent and caspase-3-mediated cell apoptosis in
      sheep bronchial epithelial cells in response to M. ovipneumoniae infections.

PMID- 28494932
TI  - Comparison of growth performance and immune parameters of three commercial
      chicken lines used in organic production.
AB  - Owing to the higher demands for avoiding medication and antibiotics, health
      status of the production animals plays an important role in the poultry industry,
      especially in organic poultry systems. Immunity plays a major role in keeping the
      host free from disease, and it is evident that the host's genetic make-up
      influences immunity and disease resistance/susceptibility in chickens.
      Previously, breeding strategies aimed at selection for resistance against
      specific diseases with the risk of creating less disease resistance against other
      pathogens. Changing breeding strategies towards selection of chickens with a more
      general and broad disease resistance or robustness may therefore improve the
      overall health status, animal welfare, and food security in the poultry
      production. The aim of this study was therefore to compare the immunocompetence
      of the presumed "robust" Hellevad chickens with two chicken lines widely used in
      organic production, Bovans Brown (Bovans) and Hisex White (Hisex). The chickens
      were subjected to a routine vaccination program comprising one parasite and four
      viral vaccines. The current study indicates that considerable differences in
      immunocompetence may exist between commercial layer lines used in organic
      production. The Hellevad chickens were found to have higher body weight at the
      end of the experiment (17 weeks of age) than the other two lines. Furthermore,
      Hellevad and Hisex chickens were found to have higher levels of humoral innate
      immunity with regard to sample to positive ratio of natural antibodies in serum
      and concentration of mannose-binding lectin in serum as compared to Bovans.
      Moreover, indications of an inflammatory response were observed in the Bovans at
      week 5, corresponding to 1 week after vaccination with live infectious bursal
      disease virus. With regard to adaptive immune parameters such as IgY
      concentration in blood and infectious bursal disease virus (IBDV)-specific
      antibody titres, the Hellevad and Hisex chickens had lower levels than the
      Bovans. How the differences observed in growth and immune parameters in the three
      chicken lines influence the immune protection against infection needs to be
      studied further.

PMID- 28494933
TI  - Comparative phenotypic and functional analyses of the effects of autologous
      plasma and recombinant human macrophage-colony stimulating factor (M-CSF) on
      porcine monocyte to macrophage differentiation.
AB  - Porcine monocyte-derived macrophages (moMPhi) have been employed as a model cell
      in numerous studies of the porcine immune system. However, the lack of a
      standardized method for moMPhi differentiation hampers the comparison of results
      coming from the use of different laboratory protocols. In this study we compared
      the use of varying concentrations of autologous plasma (10, 20 and 30% v/v) or
      recombinant human macrophage-colony stimulating factor (hM-CSF; 50, 100, and
      200ng/ml) to differentiate porcine monocytes into macrophages. Changes in cell
      morphology and surface marker expression were assessed by confocal microscopy and
      flow cytometry. Macrophage differentiation was evaluated by analysing TNF-alpha
      response to LPS stimulation and determining cytokine secretion patterns under
      both basal conditions and after classical and alternative activation. The effects
      of the differentiation methods on metabolic activity and susceptibility to
      infection with the myelotropic African swine fever virus (ASFV) were also
      evaluated. Monocytes cultured using the different culture conditions tested
      augmented in dimension and cellular complexity, but increasing porcine plasma
      concentrations resulted in a dose dependent enhancement in granularity and a
      marked pleomorphism. As expected, CD163, MHC class II DR and CD203a expression
      were up-regulated in both hM-CSF (M-CSF-moMPhi) and autologous plasma cultured
      macrophages (AP-moMPhi), although a lower percentage of CD163+ cells were found
      following differentiation with high percentages of porcine plasma. We observed
      enhanced number of viable cells using high concentration of hM-CSF compared to
      porcine plasma, suggesting a proliferative effect. Irrespective of
      differentiation conditions, monocyte differentiation into macrophages resulted in
      an increased susceptibility to ASFV and yielded larger amounts of LPS-induced TNF
      alpha. AP-moMPhi showed a higher basal release of IL-1RA compared to those
      cultured with hM-CSF and displayed a reduced ability to respond to classical
      activation, suggesting that the use of high percentages of porcine plasma led to
      the acquisition of a M2-like phenotype. We conclude that all the protocols tested
      in this study can be considered as suitable to produce porcine moMPhi, although
      the use of hM-CSF provides high responsiveness to M1 polarization. Since a higher
      phenotypic and functional inter-animal variability was observed in AP-moMPhi, we
      propose that the use of low concentration of hM-CSF should be adopted as the
      method of choice to provide a better reproducibility between experiments.

PMID- 28494934
TI  - The expression of NKG2D on porcine IEL and its possible relation to the adaptive
      intestinal immune system.
AB  - The gastrointestinal tract contains a multitude of components which include
      intraepithelial lymphocytes (IEL). IELs have been reported to express a variety
      of surface receptors that enable cross talk among various cell populations. The
      purpose of the reported investigation was to determine which IEL populations
      express the natural killer cell receptor NKG2D which is an activating receptor
      that plays a role in cytolytic responses. In a feeding experiment with piglets,
      IELs were isolated from jejunal tissue at three different stages post weaning.
      The time dependent development of different cell populations was evaluated and an
      elevated number of lymphocytes (CD45+) shortly after weaning was observed
      compared to later time points. The number of T cells (CD3), including cytotoxic T
      cells (CD8beta/CD16-), appeared to be particularly affected by the weaning
      period. Correlation analysis revealed an association between the NKG2D expression
      in jejunal tissue and the frequency of lymphocytes, esp. CD8beta+ cytotoxic T
      cells. Gene expression analysis of NKG2D were performed on several isolated IEL
      populations and support the hypothesis that cytotoxic T cells (CD8beta) in the
      porcine gut epithelium are capable of communicating with the surrounding
      enterocytes and inducing immune reactions via NKG2D. Unlike previous observations
      in porcine blood, the gammadelta T cells of the gut epithelium also showed
      expression of the stress factor binding NKG2D receptor. Subsequent analysis of
      the isolated IELs revealed that T cells appear to only express the receptor after
      isolation with an anti-CD3 mab, indicating that a previous stimulation of the
      TCR/CD3 complex may reinforce this signal transduction pathway.

PMID- 28494935
TI  - Corrigendum to "Transplantation of VEGFl65-overexpressing vascular endothelial
      progenitor cells relieves endothelial injury after deep vein thrombectomy"
      [Thromb. Res. 137 (2016) 41-45].

PMID- 28494936
TI  - Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell
      Clones of Sjogren's Syndrome.
AB  - Although it is important to clarify the pathogenic functions of T cells in human
      samples, their examination is often limited due to difficulty in obtaining
      sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells,
      especially in autoimmune diseases. We describe the generation of DCs from induced
      pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T
      cell clones from a patient with Sjogren's syndrome (SS) into iPSCs, which were
      differentiated into DCs (T-iPS-DCs). T-iPS-DCs had dendritic cell-like
      morphology, and expressed CD11c, HLA-DR, CD80, CD86, and also BDCA-3. Compared
      with monocyte-derived DCs, the capacity for antigen processing was similar, and T
      iPS-DCs induced the proliferative response of autoreactive CD4+ T cells.
      Moreover, we could evaluate T cell functions of the patient with SS. In
      conclusion, we obtained adequate numbers of DCs from T-iPSCs, which could be used
      to characterize pathogenic T cells in autoimmune diseases such as SS.

PMID- 28494937
TI  - MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune
      Murine Models: Type 1 Diabetes and Uveoretinitis.
AB  - Accumulating evidence shows that extracellular vesicles (EVs) produced by
      mesenchymal stem/stromal cells (MSCs) exert their therapeutic effects in several
      disease models. We previously demonstrated that MSCs suppress autoimmunity in
      models of type 1 diabetes (T1D) and experimental autoimmune uveoretinitis (EAU).
      Therefore, here, we investigated the therapeutic potential of MSC-derived EVs
      using our established mouse models for autoimmune diseases affecting the pancreas
      and the eye: T1D and EAU. The data demonstrate that MSC-derived EVs effectively
      prevent the onset of disease in both T1D and EAU. In addition, the mixed
      lymphocyte reaction assay with MSC-derived EVs indicated that EVs inhibit
      activation of antigen-presenting cells and suppress development of T helper 1
      (Th1) and Th17 cells. These results raise the possibility that MSC-derived EVs
      may be an alternative to cell therapy for autoimmune disease prevention.

PMID- 28494938
TI  - PI3K/AKT/mTOR Signaling Mediates Valproic Acid-Induced Neuronal Differentiation
      of Neural Stem Cells through Epigenetic Modifications.
AB  - Although valproic acid (VPA), has been shown to induce neuronal differentiation
      of neural stem cells (NSCs), the underlying mechanisms remain poorly understood.
      Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is
      involved in the neuronal differentiation of VPA-induced NSCs. Our data
      demonstrated that mTOR activation not only promoted but also was necessary for
      the neuronal differentiation of NSCs induced by VPA. We further found that
      inhibition of mTOR signaling blocked demethylation of neuron-specific gene
      neurogenin 1 (Ngn1) regulatory element in induced cells. These are correlated
      with the significant alterations of passive DNA demethylation and the active DNA
      demethylation pathway in the Ngn1 promoter, but not the suppression of lysine
      specific histone methylation and acetylation in the promoter region of Ngn1.
      These findings highlight a potentially important role for mTOR signaling, by
      working together with DNA demethylation, to influence the fate of NSCs via
      regulating the expression of Ngn1 in VPA-induced neuronal differentiation of
      NSCs.

PMID- 28494939
TI  - Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis.
AB  - Clinical trials of stem cell therapy to treat ischemic heart disease primarily
      use heterogeneous stem cell populations. Small benefits occur via paracrine
      mechanisms that include stimulating angiogenesis, and increased understanding of
      these mechanisms would help to improve patient outcomes. Cardiosphere-derived
      cells (CDCs) are an example of these heterogeneous stem cell populations,
      cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds
      specific transforming growth factor beta (TGFbeta) family ligands, including bone
      morphogenetic protein 9 (BMP9). In endothelial cells endoglin regulates
      angiogenic responses, and we therefore hypothesized that endoglin is required to
      promote the paracrine pro-angiogenic properties of CDCs. Cre/LoxP technology was
      used to genetically manipulate endoglin expression in CDCs, and we found that the
      pro-angiogenic properties of the CDC secretome are endoglin dependent both in
      vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs
      restores their pro-angiogenic paracrine properties. As BMP9 signaling is normally
      required to maintain endoglin expression, we propose that media containing BMP9
      could be critical for therapeutic CDC preparation.

PMID- 28494940
TI  - Differentiation-Defective Human Induced Pluripotent Stem Cells Reveal Strengths
      and Limitations of the Teratoma Assay and In Vitro Pluripotency Assays.
AB  - The ability to form teratomas in vivo containing multiple somatic cell types is
      regarded as functional evidence of pluripotency for human pluripotent stem cells
      (hPSCs). Since the Teratoma assay is animal dependent, laborious, and only
      qualitative, the PluriTest and the hPSC ScoreCard assay have been developed as in
      vitro alternatives. Here we compared normal hPSCs, induced hPSCs (hiPSCs) with
      reactivated reprogramming transgenes, and human embryonal carcinoma cells (hECs)
      in these assays. While normal hPSCs gave rise to typical teratomas, the
      xenografts of the hECs and the hiPSCs with reactivated reprogramming transgenes
      were largely undifferentiated and malignant. The hPSC ScoreCard assay confirmed
      the line-specific differentiation propensities in vitro. However, when
      undifferentiated cells were analyzed by the PluriTest, only hECs were identified
      as abnormal whereas all other cell lines were indistinguishable and resembled
      normal hPSCs. Our results indicate that pluripotency assays are best selected on
      the basis of intended downstream applications.

PMID- 28494941
TI  - Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using
      CRISPR/Cas9.
AB  - Efficient methodologies for recreating cancer-associated chromosome
      translocations are in high demand as tools for investigating how such events
      initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics
      of these complex rearrangements at native loci while maintaining the architecture
      and regulatory elements. However, the CRISPR system remains inefficient in human
      stem cells. Here, we compared three strategies aimed at enhancing the efficiency
      of the CRISPR-mediated t(11;22) translocation in human stem cells, including
      mesenchymal and induced pluripotent stem cells: (1) using end-joining DNA
      processing factors involved in repair mechanisms, or (2) ssODNs to guide the
      ligation of the double-strand break ends generated by CRISPR/Cas9; and (3) all-in
      one plasmid or ribonucleoprotein complex-based approaches. We report that the
      generation of targeted t(11;22) is significantly increased by using a combination
      of ribonucleoprotein complexes and ssODNs. The CRISPR/Cas9-mediated generation of
      targeted t(11;22) in human stem cells opens up new avenues in modeling Ewing
      sarcoma.

PMID- 28494943
TI  - Kinematic analysis of the scaphoid using gated four-dimensional CT.
AB  - AIM: To investigate the kinematics of the scaphoid while the wrist was in
      radioulnar motion using gated four-dimensional computed tomography (4DCT)
      imaging. MATERIALS AND METHODS: Six cadaveric wrist specimens were scanned in the
      following order of capsulotomy and ligament sectioning: (1) ligaments intact, (2)
      capsulotomy, (3) scapholunate ligament division, and lastly, (4) lunotriquetral
      ligament division. A three-dimensional model was then reconstructed to analyse
      the translation and angular displacements of the scaphoid. RESULTS: The magnitude
      of displacement was found to increase with each consecutive ligament sectioning.
      Translation along the y-axis was statistically significant, with the scaphoid
      shifting up to 1.39 mm from its original position after complete sectioning of
      the ligaments while the wrist was deviating radially. Angular displacement about
      all three axes was statistically significant, with the highest occurring in the
      flexion-extension plane when the scaphoid flexed by 9.1 degrees  from its
      original position after total sectioning of the ligaments. CONCLUSION: The
      present study showed that changes in the kinematics of the scaphoid can be
      detected using 4DCT, thus demonstrating its feasibility in the diagnosis of
      dynamic carpal instability, which only presents during motion.

PMID- 28494942
TI  - RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA+ and
      SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.
AB  - POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is
      required for maintenance of stem cell state through mechanisms not known in
      detail. To explore how POLR3G regulates stem cell state, we carried out deep
      sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs and
      regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a
      specific subset of the hPSC transcriptome, including multiple transcript types,
      such as protein-coding genes, long intervening non-coding RNAs, microRNAs and
      small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is
      in the maintenance rather than repression of transcription. The majority of
      POLR3G polyA+ transcriptome is regulated during differentiation, and the key
      pluripotency factors bind to the promoters of at least 30% of the POLR3G
      regulated transcripts. Among the direct targets of POLR3G, POLG is potentially
      important in sustaining stem cell status in a POLR3G-dependent manner.

PMID- 28494944
TI  - How to Make a Worm Twitch.

PMID- 28494945
TI  - Tug of War at the Cell-Matrix Interface.

PMID- 28494947
TI  - AESOP: A Python Library for Investigating Electrostatics in Protein Interactions.
AB  - Electric fields often play a role in guiding the association of protein
      complexes. Such interactions can be further engineered to accelerate complex
      association, resulting in protein systems with increased productivity. This is
      especially true for enzymes where reaction rates are typically diffusion limited.
      To facilitate quantitative comparisons of electrostatics in protein families and
      to describe electrostatic contributions of individual amino acids, we previously
      developed a computational framework called AESOP. We now implement this
      computational tool in Python with increased usability and the capability of
      performing calculations in parallel. AESOP utilizes PDB2PQR and Adaptive Poisson
      Boltzmann Solver to generate grid-based electrostatic potential files for protein
      structures provided by the end user. There are methods within AESOP for
      quantitatively comparing sets of grid-based electrostatic potentials in terms of
      similarity or generating ensembles of electrostatic potential files for a library
      of mutants to quantify the effects of perturbations in protein structure and
      protein-protein association.

PMID- 28494946
TI  - Tropomodulins and Leiomodins: Actin Pointed End Caps and Nucleators in Muscles.
AB  - Cytoskeletal structures characterized by actin filaments with uniform lengths,
      including the thin filaments of striated muscles and the spectrin-based membrane
      skeleton, use barbed and pointed-end capping proteins to control subunit
      addition/dissociation at filament ends. While several proteins cap the barbed
      end, tropomodulins (Tmods), a family of four closely related isoforms in
      vertebrates, are the only proteins known to specifically cap the pointed end.
      Tmods are ~350 amino acids in length, and comprise alternating tropomyosin- and
      actin-binding sites (TMBS1, ABS1, TMBS2, and ABS2). Leiomodins (Lmods) are
      related in sequence to Tmods, but display important differences, including most
      notably the lack of TMBS2 and the presence of a C-terminal extension featuring a
      proline-rich domain and an actin-binding WASP-Homology 2 domain. The Lmod
      subfamily comprises three somewhat divergent isoforms expressed predominantly in
      muscle cells. Biochemically, Lmods differ from Tmods, acting as powerful
      nucleators of actin polymerization, not capping proteins. Structurally, Lmods and
      Tmods display crucial differences that correlate well with their different
      biochemical activities. Physiologically, loss of Lmods in striated muscle results
      in cardiomyopathy or nemaline myopathy, whereas complete loss of Tmods leads to
      failure of myofibril assembly and developmental defects. Yet, interpretation of
      some of the in vivo data has led to the idea that Tmods and Lmods are
      interchangeable or, at best, different variants of two subfamilies of pointed-end
      capping proteins. Here, we review and contrast the existing literature on Tmods
      and Lmods, and propose a model of Lmod function that attempts to reconcile the in
      vitro and in vivo data, whereby Lmods nucleate actin filaments that are
      subsequently capped by Tmods during sarcomere assembly, turnover, and repair.

PMID- 28494948
TI  - Microvessel Chaste: An Open Library for Spatial Modeling of Vascularized Tissues.
AB  - Spatial models of vascularized tissues are widely used in computational
      physiology. We introduce a software library for composing multiscale,
      multiphysics models for applications including tumor growth, angiogenesis,
      osteogenesis, coronary perfusion, and oxygen delivery. Composition of such models
      is time consuming, with many researchers writing custom software. Recent advances
      in imaging have produced detailed three-dimensional (3D) datasets of vascularized
      tissues at the scale of individual cells. To fully exploit such data there is an
      increasing need for software that allows user-friendly composition of efficient,
      3D models of vascularized tissues, and comparison of predictions with in vivo or
      in vitro experiments and alternative computational formulations. Microvessel
      Chaste can be used to build simulations of vessel growth and adaptation in
      response to mechanical and chemical stimuli; intra- and extravascular transport
      of nutrients, growth factors and drugs; and cell proliferation in complex 3D
      geometries. In addition, it can be used to develop custom software for
      integrating modeling with experimental data processing workflows, facilitated by
      a comprehensive Python interface to solvers implemented in C++. This article
      links to two reproducible example problems, showing how the library can be used
      to build simulations of tumor growth and angiogenesis with realistic vessel
      networks.

PMID- 28494949
TI  - Molecular Counting with Localization Microscopy: A Bayesian Estimate Based on
      Fluorophore Statistics.
AB  - Superresolved localization microscopy has the potential to serve as an accurate,
      single-cell technique for counting the abundance of intracellular molecules.
      However, the stochastic blinking of single fluorophores can introduce large
      uncertainties into the final count. Here we provide a theoretical foundation for
      applying superresolved localization microscopy to the problem of molecular
      counting based on the distribution of blinking events from a single fluorophore.
      We also show that by redundantly tagging single molecules with multiple, blinking
      fluorophores, the accuracy of the technique can be enhanced by harnessing the
      central limit theorem. The coefficient of variation then, for the number of
      molecules M estimated from a given number of blinks B, scales like ~1/Nl, where
      Nl is the mean number of labels on a target. As an example, we apply our theory
      to the challenging problem of quantifying the cell-to-cell variability of plasmid
      copy number in bacteria.

PMID- 28494950
TI  - Simultaneous Determination of Two Subdomain Folding Rates Using the "Transfer
      Quench" Method.
AB  - The investigation of the mechanism of protein folding is complicated by the
      context dependence of the rates of intramolecular contact formation. Methods
      based on site-specific labeling and ultrafast spectroscopic detection of
      fluorescence signals were developed for monitoring the rates of individual
      subdomain folding transitions in situ, in the context of the whole molecule.
      However, each site-specific labeling modification might affect rates of folding
      of near-neighbor structural elements, and thus limit the ability to resolve fine
      differences in rates of folding of these elements. Therefore, it is highly
      desirable to be able to study the rates of folding of two or more neighboring
      subdomain structures using a single mutant to facilitate resolution of the order
      and interdependence of such steps. Here, we report the development of the
      "Transfer-Quench" method for measuring the rate of formation of two structural
      elements using a single triple-labeled mutant. This method is based on Forster
      resonance energy transfer combined with fluorescence quenching. We placed the
      donor and acceptor at the loop ends, and a quencher at an alpha-helical element
      involved in the node forming the loop. The folding of the triple-labeled mutant
      is monitored by the acceptor emission. The formation of nonlocal contact (loop
      closure) increases the time-dependent acceptor emission, while the closure of the
      labeled helix turn reduces this emission. The method was applied in a study of
      the folding mechanism of the common model protein, the B domain of staphylococcal
      protein A. Only natural amino acids were used as probes, and thus possible
      structural perturbations were minimized. Tyr and Trp residues served as donor and
      acceptor at the ends of a long loop between helices I and II, and a Cys residue
      as a quencher for the acceptor. We found that the closure of the loop (segment 14
      33) occurs with the same rate constant as the nucleation of helix HII (segment 33
      29), in line with the nucleation-condensation model.

PMID- 28494951
TI  - The N-Terminal Domain of Ribosomal Protein L9 Folds via a Diffuse and Delocalized
      Transition State.
AB  - The N-terminal domain of L9 (NTL9) is a 56-residue mixed alpha-beta protein that
      lacks disulfides, does not bind cofactors, and folds reversibly. NTL9 has been
      widely used as a model system for experimental and computational studies of
      protein folding and for investigations of the unfolded state. The role of side
      chain interactions in the folding of NTL9 is probed by mutational analysis. phi
      values, which represent the ratio of the change in the log of the folding rate
      upon mutation to the change in the log of the equilibrium constant for folding,
      are reported for 25 point mutations and 15 double mutants. All phi-values are
      small, with an average over all sites probed of only 0.19 and a largest value of
      0.4. The effect of modulating unfolded-state interactions is studied by measuring
      phi-values in second- site mutants and under solvent conditions that perturb
      unfolded-state energetics in a defined way. Neither of these alterations
      significantly affects the distribution of phi-values. The results, combined with
      those of earlier studies that probe the role of hydrogen-bond formation in
      folding and the burial of surface area, reveal that the transition state for
      folding contains extensive backbone structure and buries a significant fraction
      of hydrophobic surface area, but lacks well developed side-chain-side-chain
      interactions. The folding transition state for NTL9 does not contain a specific
      "nucleus" consisting of a few key residues; rather, it involves extensive
      backbone hydrogen bonding and partially formed structure delocalized over almost
      the entire domain. The potential generality of these observations is discussed.

PMID- 28494952
TI  - Fast Protein Translation Can Promote Co- and Posttranslational Folding of
      Misfolding-Prone Proteins.
AB  - Chemical kinetic modeling has previously been used to predict that fast
      translating codons can enhance cotranslational protein folding by helping to
      avoid misfolded intermediates. Consistent with this prediction, protein
      aggregation in yeast and worms was observed to increase when translation was
      globally slowed down, possibly due to increased cotranslational misfolding.
      Observation of similar behavior in molecular simulations would confirm
      predictions from the simpler chemical kinetic model and provide a molecular
      perspective on cotranslational folding, misfolding, and the impact of translation
      speed on these processes. All-atom simulations cannot reach the timescales
      relevant to protein synthesis, and most conventional structure-based coarse
      grained models do not allow for nonnative structure formation. Here, we introduce
      a protocol to incorporate misfolding using the functional forms of publicly
      available force fields. With this model we create two artificial proteins that
      are capable of undergoing structural transitions between a native and a misfolded
      conformation and simulate their synthesis by the ribosome. Consistent with the
      chemical kinetic predictions, we find that rapid synthesis of misfolding-prone
      nascent-chain segments increases the fraction of folded proteins by kinetically
      partitioning more molecules through on-pathway intermediates, decreasing the
      likelihood of sampling misfolded conformations. Novel to this study, to our
      knowledge, we observe that differences in protein dynamics, arising from
      different translation-elongation schedules, can persist long after the nascent
      protein has been released from the ribosome, and that a sufficient level of
      energetic frustration is needed for fast-translating codons to be beneficial for
      folding. These results provide further evidence that fast-translating codons can
      be as biologically important as pause sites in coordinating cotranslational
      folding.

PMID- 28494953
TI  - Analysis of O2-binding Sites in Proteins Using Gas-Pressure NMR Spectroscopy:
      Outer Surface Protein A.
AB  - Internal cavities in proteins produce conformational fluctuations and enable the
      binding of small ligands. Here, we report a NMR analysis of O2-binding sites by
      O2-induced paramagnetic relaxation enhancements (PREs) on amide groups of
      proteins in solution. Outer surface protein A contains a nonglobular single-layer
      beta-sheet that connects the N- and C-terminal globular domains. Several cavities
      have been observed in both domains of the crystallized protein structure. The
      receptor-binding sites are occluded and line the largest cavity of the C-terminal
      domain. We observed significant O2-induced PREs for amide protons located around
      the largest cavity and at the central beta-sheet. We suggested three potential O2
      accessible sites in the protein based on the 1/r6 distance dependence of the PRE.
      Two sites were in or close to the largest cavity and the third site was in the
      surface crevice of the central beta-sheet. These results provide, to our
      knowledge, the first evidence of ligand binding to the surface crevice and cavity
      of the protein in solution. Because O2 generally binds more specifically to
      hydrophobic rather than hydrophilic cavities within a protein, the results also
      indicated that the receptor-binding sites lining the largest cavity were in the
      hydrophobic environment in the ground-state conformation. Molecular dynamics
      simulations permitted the visualization of the rotational and translational
      motions of O2 within the largest cavity, egress of O2 from the cavity, and
      ingress of O2 in the surface crevice of the beta-sheet. These molecular dynamics
      simulation results qualitatively explained the O2-induced changes in NMR
      observations. Exploring cavities that are sufficiently dynamic to enable access
      by small molecules can be a useful strategy for the design of stable proteins and
      their ligands.

PMID- 28494954
TI  - Competing Pathways and Multiple Folding Nuclei in a Large Multidomain Protein,
      Luciferase.
AB  - Proteins obtain their final functional configuration through incremental folding
      with many intermediate steps in the folding pathway. If known, these intermediate
      steps could be valuable new targets for designing therapeutics and the sequence
      of events could elucidate the mechanism of refolding. However, determining these
      intermediate steps is hardly an easy feat, and has been elusive for most
      proteins, especially large, multidomain proteins. Here, we effectively map part
      of the folding pathway for the model large multidomain protein, Luciferase, by
      combining single-molecule force-spectroscopy experiments and coarse-grained
      simulation. Single-molecule refolding experiments reveal the initial nucleation
      of folding while simulations corroborate these stable core structures of
      Luciferase, and indicate the relative propensities for each to propagate to the
      final folded native state. Both experimental refolding and Monte Carlo
      simulations of Markov state models generated from simulation reveal that
      Luciferase most often folds along a pathway originating from the nucleation of
      the N-terminal domain, and that this pathway is the least likely to form
      nonnative structures. We then engineer truncated variants of Luciferase whose
      sequences corresponded to the putative structure from simulation and we use
      atomic force spectroscopy to determine their unfolding and stability. These
      experimental results corroborate the structures predicted from the folding
      simulation and strongly suggest that they are intermediates along the folding
      pathway. Taken together, our results suggest that initial Luciferase refolding
      occurs along a vectorial pathway and also suggest a mechanism that chaperones may
      exploit to prevent misfolding.

PMID- 28494955
TI  - Environmental Calcium Controls Alternate Physical States of the Caulobacter
      Surface Layer.
AB  - Surface layers (S-layers) are paracrystalline, proteinaceous structures found in
      most archaea and many bacteria. Often the outermost cell envelope component, S
      layers serve diverse functions including aiding pathogenicity and protecting
      against predators. We report that the S-layer of Caulobacter crescentus exhibits
      calcium-mediated structural plasticity, switching irreversibly between an
      amorphous aggregate state and the crystalline state. This finding invalidates the
      common assumption that S-layers serve only as static wall-like structures. In
      vitro, the Caulobacter S-layer protein, RsaA, enters the aggregate state at
      physiological temperatures and low divalent calcium ion concentrations. At higher
      concentrations, calcium ions stabilize monomeric RsaA, which can then transition
      to the two-dimensional crystalline state. Caulobacter requires micromolar
      concentrations of calcium for normal growth and development. Without an S-layer,
      Caulobacter is even more sensitive to changes in environmental calcium
      concentration. Therefore, this structurally dynamic S-layer responds to
      environmental conditions as an ion sensor and protects Caulobacter from calcium
      deficiency stress, a unique mechanism of bacterial adaptation. These findings
      provide a biochemical and physiological basis for RsaA's calcium-binding
      behavior, which extends far beyond calcium's commonly accepted role in aiding S
      layer biogenesis or oligomerization and demonstrates a connection to cellular
      fitness.

PMID- 28494956
TI  - Resolution of Submillisecond Kinetics of Multiple Reaction Pathways for Lactate
      Dehydrogenase.
AB  - Enzymes are known to exhibit conformational flexibility. An important consequence
      of this flexibility is that the same enzyme reaction can occur via multiple
      reaction pathways on a reaction landscape. A model enzyme for the study of
      reaction landscapes is lactate dehydrogenase. We have previously used temperature
      jump (T-jump) methods to demonstrate that the reaction landscape of lactate
      dehydrogenase branches at multiple points creating pathways with varied
      reactivity. A limitation of this previous work is that the T-jump method makes
      only small perturbations to equilibrium and may not report conclusively on all
      steps in a reaction. Therefore, interpreting T-jump results of lactate
      dehydrogenase kinetics has required extensive computational modeling work. Rapid
      mixing methods offer a complementary approach that can access large perturbations
      from equilibrium; however, traditional enzyme mixing methods like stopped-flow do
      not allow for the observation of fast protein dynamics. In this report, we apply
      a microfluidic rapid mixing device with a mixing time of <100 MUs that allows us
      to study these fast dynamics and the catalytic redox step of the enzyme reaction.
      Additionally, we report UV absorbance and emission T-jump results with improved
      signal-to-noise ratio at fast times. The combination of mixing and T-jump results
      yields an unprecedented view of lactate dehydrogenase enzymology, confirming the
      timescale of substrate-induced conformational change and presence of multiple
      reaction pathways.

PMID- 28494957
TI  - Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from
      Oxidation.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is
      involved in a growing number of functions in peripheral tissues. Recent studies
      have shown nonpharmacological functions of 5-HT linked to its chemical
      properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid
      membranes and, on the other hand, protect red blood cells through a mechanism
      independent of its specific receptors. To better understand these underevaluated
      properties of 5-HT, we combined biochemical, biophysical, and molecular dynamics
      simulations approaches to characterize, at the molecular level, the antioxidant
      capacity of 5-HT and its interaction with lipid membranes. To do so, 5-HT was
      added to red blood cells and lipid membranes bearing different degrees of
      unsaturation. Our results demonstrate that 5-HT acts as a potent antioxidant and
      binds with a superior affinity to lipids with unsaturation on both alkyl chains.
      We show that 5-HT locates at the hydrophobic-hydrophilic interface, below the
      glycerol group. This interfacial location is stabilized by hydrogen bonds between
      the 5-HT hydroxyl group and lipid headgroups and allows 5-HT to intercept
      reactive oxygen species, preventing membrane oxidation. Experimental and
      molecular dynamics simulations using membrane enriched with oxidized lipids
      converge to further reveal that 5-HT contributes to the termination of lipid
      peroxidation by direct interaction with active groups of these lipids and could
      also contribute to limit the production of new radicals. Taken together, our
      results identify 5-HT as a potent inhibitor of lipid peroxidation and offer a
      different perspective on the role of this pleiotropic molecule.

PMID- 28494959
TI  - Mechanosensitive Conformation of Vinculin Regulates Its Binding to MAPK1.
AB  - Extracellular matrix stiffness sensing by living cells is known to play a major
      role in a variety of cell mechanobiological processes, such as migration and
      differentiation. Various membrane and cytoplasmic proteins are involved in
      transmitting and transducing environmental signals to biochemical cascades.
      Protein kinases play a key role in regulating the activity of focal adhesion
      proteins. Recently, an interaction between mitogen-activated protein kinase
      (MAPK1) and vinculin was experimentally shown to mediate this process. Here, we
      adopt a molecular modeling approach to further investigate this interaction and
      its possible regulatory effects. Using a combination of data-driven flexible
      docking and molecular dynamics simulations guided by previous experimental
      studies, we predict the structure of the MAPK1-vinculin complex. Furthermore, by
      comparing the association of MAPK1 with open versus closed vinculin, we
      demonstrate that MAPK1 exhibits preferential binding toward the open conformation
      of vinculin, suggesting that the MAPK1-vinculin interaction is conformationally
      selective. Finally, we demonstrate that changes in the size of the D3-D4 cleft
      provide a structural basis for the conformational selectivity of the interaction.

PMID- 28494958
TI  - Integrated Analysis of Intracellular Dynamics of MenaINV Cancer Cells in a 3D
      Matrix.
AB  - The intracellular environment is composed of a filamentous network that exhibits
      dynamic turnover of cytoskeletal components and internal force generation from
      molecular motors. Particle tracking microrheology enables a means to probe the
      internal mechanics and dynamics. Here, we develop an analytical model to capture
      the basic features of the active intracellular mechanical environment, including
      both thermal and motor-driven effects, and show consistency with a diverse range
      of experimental microrheology data. We further perform microrheology experiments,
      integrated with Brownian dynamics simulations of the active cytoskeleton, on
      metastatic breast cancer cells embedded in a three-dimensional collagen matrix
      with and without the presence of epidermal growth factor to probe the
      intracellular mechanical response in a physiologically mimicking scenario. Our
      results demonstrate that EGF stimulation can alter intracellular stiffness and
      power output from molecular motor-driven fluctuations in cells overexpressing an
      invasive isoform of the actin-associated protein Mena.

PMID- 28494960
TI  - Laser-Activated Polymeric Microcapsules for Ultrasound Imaging and Therapy: In
      Vitro Feasibility.
AB  - Polymeric microcapsules with a light-absorbing dye incorporated in their shell
      can generate vapor microbubbles that can be spatiotemporally controlled by pulsed
      laser irradiation. These contrast agents of 6-8 MUm in diameter can circulate
      through the vasculature, offering possibilities for ultrasound (molecular)
      imaging and targeted therapies. Here, we study the impact of such vapor bubbles
      on human endothelial cells in terms of cell poration and cell viability to
      establish the imaging and therapeutic windows. Two capsule formulations were
      used: the first one consisted of a high boiling point oil (hexadecane), whereas
      the second was loaded with a low boiling point oil (perfluoropentane). Poration
      probability was already 40% for the smallest bubbles that were formed (<7.5 MUm
      diameter), and reached 100% for the larger bubbles. The hexadecane-loaded
      capsules also produced bubbles while their shell remained intact. These
      encapsulated bubbles could therefore be used for noninvasive ultrasound imaging
      after laser activation without inducing any cell damage. The controlled and
      localized cell destruction achieved by activation of both capsule formulations
      may provide an innovative approach for specifically inducing cell death in vivo,
      e.g., for cancer therapy.

PMID- 28494961
TI  - Rolling Adhesion of Schizont Stage Malaria-Infected Red Blood Cells in Shear
      Flow.
AB  - To avoid clearance by the spleen, red blood cells infected with the human malaria
      parasite Plasmodium falciparum (iRBCs) adhere to the vascular endothelium through
      adhesive protrusions called "knobs" that the parasite induces on the surface of
      the host cell. However, the detailed relation between the developing knob
      structure and the resulting movement in shear flow is not known. Using flow
      chamber experiments on endothelial monolayers and tracking of the parasite inside
      the infected host cell, we find that trophozoites (intermediate-stage iRBCs) tend
      to flip due to their biconcave shape, whereas schizonts (late-stage iRBCs) tend
      to roll due to their almost spherical shape. We then use adhesive dynamics
      simulations for spherical cells to predict the effects of knob density and
      receptor multiplicity per knob on rolling adhesion of schizonts. We find that
      rolling adhesion requires a homogeneous coverage of the cell surface by knobs and
      that rolling adhesion becomes more stable and slower for higher knob density. Our
      experimental data suggest that schizonts are at the border between transient and
      stable rolling adhesion. They also allow us to establish an estimate for the
      molecular parameters for schizont adhesion to the vascular endothelium and to
      predict bond dynamics in the contact region.

PMID- 28494962
TI  - Nuclear Positioning and Its Translational Dynamics Are Regulated by Cell
      Geometry.
AB  - The collective activity of several molecular motors and other active processes
      generate large forces for directional motion within the cell, which is vital for
      a multitude of cellular functions such as migration, division, contraction,
      transport, and positioning of various organelles. These processes also generate a
      background of fluctuating forces, which influence intracellular dynamics and
      thereby create unique biophysical signatures, which are altered in many diseases.
      In this study, we have used the nucleus as a probe particle to understand the
      microrheological properties of altered intracellular environments by using
      micropatterning to confine cells in two structurally and functionally extreme
      geometries. We find that nuclear positional dynamics is sensitive to the
      cytoskeletal organization by studying the effect of actin polymerization and
      nuclear rigidity on the diffusive behavior of the nucleus. Taken together, our
      results suggest that mapping nuclear positional dynamics provides important
      insights into biophysical properties of the active cytoplasmic medium. These
      biophysical signatures have the potential to be used as an ultrasensitive single
      cell assay for early disease diagnostics.

PMID- 28494964
TI  - Near-Membrane Refractometry Using Supercritical Angle Fluorescence.
AB  - Total internal reflection fluorescence (TIRF) microscopy and its variants are key
      technologies for visualizing the dynamics of single molecules or organelles in
      live cells. Yet truly quantitative TIRF remains problematic. One unknown
      hampering the interpretation of evanescent-wave excited fluorescence intensities
      is the undetermined cell refractive index (RI). Here, we use a combination of
      TIRF excitation and supercritical angle fluorescence emission detection to
      directly measure the average RI in the "footprint" region of the cell during
      image acquisition. Our RI measurement is based on the determination on a back
      focal plane image of the critical angle separating evanescent and far-field
      fluorescence emission components. We validate our method by imaging mouse
      embryonic fibroblasts and BON cells. By targeting various dyes and fluorescent
      protein chimeras to vesicles, the plasma membrane, as well as mitochondria and
      the endoplasmic reticulum, we demonstrate local RI measurements with subcellular
      resolution on a standard TIRF microscope, with a removable Bertrand lens as the
      only modification. Our technique has important applications for imaging axial
      vesicle dynamics and the mitochondrial energy state or detecting metabolically
      more active cancer cells.

PMID- 28494963
TI  - Design and Properties of Genetically Encoded Probes for Sensing Macromolecular
      Crowding.
AB  - Cells are highly crowded with proteins and polynucleotides. Any reaction that
      depends on the available volume can be affected by macromolecular crowding, but
      the effects of crowding in cells are complex and difficult to track. Here, we
      present a set of Forster resonance energy transfer (FRET)-based crowding
      sensitive probes and investigate the role of the linker design. We investigate
      the sensors in vitro and in vivo and by molecular dynamics simulations. We find
      that in vitro all the probes can be compressed by crowding, with a magnitude that
      increases with the probe size, the crowder concentration, and the crowder size.
      We capture the role of the linker in a heuristic scaling model, and we find that
      compression is a function of size of the probe and volume fraction of the
      crowder. The FRET changes observed in Escherichia coli are more complicated,
      where FRET-increases and scaling behavior are observed solely with probes that
      contain the helices in the linker. The probe with the highest sensitivity to
      crowding in vivo yields the same macromolecular volume fractions as previously
      obtained from cell dry weight. The collection of new probes provides more
      detailed readouts on the macromolecular crowding than a single sensor.

PMID- 28494965
TI  - Multiscale Determinants of Delayed Afterdepolarization Amplitude in Cardiac
      Tissue.
AB  - Spontaneous calcium (Ca) waves in cardiac myocytes underlie delayed
      afterdepolarizations (DADs) that trigger cardiac arrhythmias. How these
      subcellular/cellular events overcome source-sink factors in cardiac tissue to
      generate DADs of sufficient amplitude to trigger action potentials is not fully
      understood. Here, we evaluate quantitatively how factors at the subcellular scale
      (number of Ca wave initiation sites), cellular scale (sarcoplasmic reticulum (SR)
      Ca load), and tissue scale (synchrony of Ca release in populations of myocytes)
      determine DAD features in cardiac tissue using a combined experimental and
      computational modeling approach. Isolated patch-clamped rabbit ventricular
      myocytes loaded with Fluo-4 to image intracellular Ca were rapidly paced during
      exposure to elevated extracellular Ca (2.7 mmol/L) and isoproterenol (0.25
      MUmol/L) to induce diastolic Ca waves and subthreshold DADs. As the number of
      paced beats increased from 1 to 5, SR Ca content (assessed with caffeine pulses)
      increased, the number of Ca wave initiation sites increased, integrated Ca
      transients and DADs became larger and shorter in duration, and the latency period
      to the onset of Ca waves shortened with reduced variance. In silico analysis
      using a computer model of ventricular tissue incorporating these experimental
      measurements revealed that whereas all of these factors promoted larger DADs with
      higher probability of generating triggered activity, the latency period variance
      and SR Ca load had the greatest influences. Therefore, incorporating quantitative
      experimental data into tissue level simulations reveals that increased
      intracellular Ca promotes DAD-mediated triggered activity in tissue predominantly
      by increasing both the synchrony (decreasing latency variance) of Ca waves in
      nearby myocytes and SR Ca load, whereas the number of Ca wave initiation sites
      per myocyte is less important.

PMID- 28494966
TI  - Mechanotransduction Dynamics at the Cell-Matrix Interface.
AB  - The ability of cells to sense and respond to mechanical cues from the surrounding
      environment has been implicated as a key regulator of cell differentiation,
      migration, and proliferation. The extracellular matrix (ECM) is an oft-overlooked
      component of the interface between cells and their surroundings. Cells assemble
      soluble ECM proteins into insoluble fibrils with unique mechanical properties
      that can alter the mechanical cues a cell receives. In this study, we construct a
      model that predicts the dynamics of cellular traction force generation and
      subsequent assembly of fibrils of the ECM protein fibronectin (FN). FN fibrils
      are the primary component in primordial ECM and, as such, FN assembly is a
      critical component in the cellular mechanical response. The model consists of a
      network of Hookean springs, each representing an extensible domain within an
      assembling FN fibril. As actomyosin forces stretch the spring network,
      simulations predict the resulting traction force and FN fibril formation. The
      model accurately predicts FN fibril morphometry and demonstrates a mechanism by
      which FN fibril assembly regulates traction force dynamics in response to
      mechanical stimuli and varying surrounding substrate stiffness.

PMID- 28494967
TI  - Visualizing Calcium Flux in Freely Moving Nematode Embryos.
AB  - The lack of physiological recordings from Caenorhabditis elegans embryos stands
      in stark contrast to the comprehensive anatomical and gene expression datasets
      already available. Using light-sheet fluorescence microscopy to address the
      challenges associated with functional imaging at this developmental stage, we
      recorded calcium dynamics in muscles and neurons and developed analysis
      strategies to relate activity and movement. In muscles, we found that the
      initiation of twitching was associated with a spreading calcium wave in a dorsal
      muscle bundle. Correlated activity in muscle bundles was linked with early
      twitching and eventual coordinated movement. To identify neuronal correlates of
      behavior, we monitored brainwide activity with subcellular resolution and
      identified a particularly active cell associated with muscle contractions.
      Finally, imaging neurons of a well-defined adult motor circuit, we found that
      reversals in the eggshell correlated with calcium transients in AVA interneurons.

PMID- 28494968
TI  - Bistability and Nonmonotonic Induction of the lac Operon in the Natural Lactose
      Uptake System.
AB  - The Escherichia coli lac operon is regulated by a positive feedback loop whose
      potential to generate an all-or-none response in single cells has been a paradigm
      for bistable gene expression. However, so far bistable lac induction has only
      been observed using gratuitous inducers, raising the question about the
      biological relevance of bistable lac induction in the natural setting with
      lactose as the inducer. In fact, the existing experimental evidence points to a
      graded rather than an all-or-none response in the natural lactose uptake system.
      In contrast, predictions based on computational models of the lactose uptake
      pathway remain controversial. Although some argue in favor of bistability, others
      argue against it. Here, we reinvestigate lac operon expression in single cells
      using a combined experimental/modeling approach. To this end, we parameterize a
      well-supported mathematical model using transient measurements of LacZ activity
      upon induction with different amounts of lactose. The resulting model predicts a
      monostable induction curve for the wild-type system, but indicates that
      overexpression of the LacI repressor would drive the system into the bistable
      regime. Both predictions were confirmed experimentally supporting the view that
      the wild-type lac induction circuit generates a graded response rather than
      bistability. More interestingly, we find that the lac induction curve exhibits a
      pronounced maximum at intermediate lactose concentrations. Supported by our data,
      a model-based analysis suggests that the nonmonotonic response results from
      saturation of the LacI repressor at low inducer concentrations and dilution of
      Lac enzymes due to an increased growth rate beyond the saturation point. We
      speculate that the observed maximum in the lac expression level helps to save
      cellular resources by limiting Lac enzyme expression at high inducer
      concentrations.

PMID- 28494969
TI  - Rate-Dependent Role of IKur in Human Atrial Repolarization and Atrial
      Fibrillation Maintenance.
AB  - The atrial-specific ultrarapid delayed rectifier K+ current (IKur) inactivates
      slowly but completely at depolarized voltages. The consequences for IKur rate
      dependence have not been analyzed in detail and currently available mathematical
      action-potential (AP) models do not take into account experimentally observed
      IKur inactivation dynamics. Here, we developed an updated formulation of IKur
      inactivation that accurately reproduces time-, voltage-, and frequency-dependent
      inactivation. We then modified the human atrial cardiomyocyte Courtemanche AP
      model to incorporate realistic IKur inactivation properties. Despite markedly
      different inactivation dynamics, there was no difference in AP parameters across
      a wide range of stimulation frequencies between the original and updated models.
      Using the updated model, we showed that, under physiological stimulation
      conditions, IKur does not inactivate significantly even at high atrial rates
      because the transmembrane potential spends little time at voltages associated
      with inactivation. Thus, channel dynamics are determined principally by
      activation kinetics. IKur magnitude decreases at higher rates because of AP
      changes that reduce IKur activation. Nevertheless, the relative contribution of
      IKur to AP repolarization increases at higher frequencies because of reduced
      activation of the rapid delayed-rectifier current IKr. Consequently, IKur block
      produces dose-dependent termination of simulated atrial fibrillation (AF) in the
      absence of AF-induced electrical remodeling. The inclusion of AF-related ionic
      remodeling stabilizes simulated AF and greatly reduces the predicted
      antiarrhythmic efficacy of IKur block. Our results explain a range of
      experimental observations, including recently reported positive rate-dependent
      IKur-blocking effects on human atrial APs, and provide insights relevant to the
      potential value of IKur as an antiarrhythmic target for the treatment of AF.

PMID- 28494971
TI  - Introduction to Biophysics Week: What is Biophysics?

PMID- 28494970
TI  - Image-Based Measurement of H2O2 Reaction-Diffusion in Wounded Zebrafish Larvae.
AB  - Epithelial injury induces rapid recruitment of antimicrobial leukocytes to the
      wound site. In zebrafish larvae, activation of the epithelial NADPH oxidase Duox
      at the wound margin is required early during this response. Before injury,
      leukocytes are near the vascular region, that is, ~100-300 MUm away from the
      injury site. How Duox establishes long-range signaling to leukocytes is unclear.
      We conceived that extracellular hydrogen peroxide (H2O2) generated by Duox
      diffuses through the tissue to directly regulate chemotactic signaling in these
      cells. But before it can oxidize cellular proteins, H2O2 must get past the
      antioxidant barriers that protect the cellular proteome. To test whether, or on
      which length scales this occurs during physiological wound signaling, we
      developed a computational method based on reaction-diffusion principles that
      infers H2O2 degradation rates from intravital H2O2-biosensor imaging data. Our
      results indicate that at high tissue H2O2 levels the peroxiredoxin-thioredoxin
      antioxidant chain becomes overwhelmed, and H2O2 degradation stalls or ceases.
      Although the wound H2O2 gradient reaches deep into the tissue, it likely
      overcomes antioxidant barriers only within ~30 MUm of the wound margin. Thus,
      Duox-mediated long-range signaling may require other spatial relay mechanisms
      besides extracellular H2O2 diffusion.

PMID- 28494973
TI  - Retention in high-performance liquid chromatography at -196 degrees C.
AB  - Recently, we have developed ultralow-temperature high-performance liquid
      chromatography (HPLC) at -196 degrees C using liquid nitrogen-based mobile
      phases. In this study, a retention model for ultralow-temperature HPLC, in which
      adsorption exchange and "pseudo partition" modes are combined, is proposed to
      describe the effect of the mobile phase composition on the retention of analytes.
      The experimental results agreed well with the equation of the proposed model. It
      was revealed that, in the low and high additive concentration regions, adsorption
      exchange and pseudo partition retention, respectively, dominate the analyte
      retention. The difference in the retention behavior between bare-silica and
      octadecylsilyl-modified silica (ODS) columns was also studied. Retention of
      alkanes in the ODS column was greater than that in the bare-silica one. Addition
      of both ethane and ethylene to the mobile phase in the ODS column afforded the
      elution of propylene, which was not eluted with the bare-silica column at -196
      degrees C.

PMID- 28494972
TI  - Synaptic Impairment in Alzheimer's Disease: A Dysregulated Symphony.
AB  - Alzheimer's disease (AD) is characterized by memory loss, cognitive decline, and
      devastating neurodegeneration, not only as a result of the extracellular
      accumulation of beta-amyloid peptide (Abeta) and intracellular accumulation of
      tau, but also as a consequence of the dysfunction and loss of synapses. Although
      significant advances have been made in our understanding of the relationship of
      the pathological role of Abeta and tau in synapse dysfunction, several questions
      remain as to how Abeta and tau interdependently cause impairments in synaptic
      function in AD. Overall, more insight into these questions should enable
      researchers in this field to develop novel therapeutic targets to mitigate or
      delay the cognitive deficits associated with this devastating disease.

PMID- 28494975
TI  - Navigating Choices Among a Sea of Comorbidities.

PMID- 28494974
TI  - Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT
      CRT Long-Term Follow-Up.
AB  - BACKGROUND: Data regarding cardiac resynchronization therapy (CRT) in patients
      with multiple comorbidities are limited. OBJECTIVES: This study evaluated the
      association of multiple comorbidities with the benefits of CRT over implantable
      cardioverter-defibrillator (ICD) alone. METHODS: We examined 1,214 MADIT-CRT
      (Multicenter Automatic Defibrillator Implantation Trial with Cardiac
      Resynchronization Therapy) study patients with left bundle branch block (LBBB)
      and 0, 1, 2, or >=3 comorbidities, including renal dysfunction, hypertension
      (HTN), diabetes, coronary artery disease, history of atrial arrhythmias, history
      of ventricular arrhythmias, current smoking, and cerebrovascular accident. In an
      adjusted analysis, we analyzed risk of heart failure (HF) events or death by
      comorbidity group in all patients and in patients with CRT with defibrillator
      (CRT-D) versus ICD. Then we examined percent change in left ventricular (LV) end
      diastolic volume, LV end-systolic volume, LV ejection fraction, left atrial
      volume, and LV dyssynchrony at 1-year in CRT-D patients by comorbidity group.
      RESULTS: There was an inverse relationship between comorbidity burden and
      improvements in LV end-systolic volume, LV end-diastolic volume, left ventricular
      ejection fraction, left atrial volume, and LV dyssynchrony. In an adjusted model,
      there was an increasing risk of death or nonfatal HF events with increasing
      comorbidity burden regardless of treatment group (p < 0.001). During a mean
      follow-up of 4.65 years, there was no interaction with respect to comorbidity
      burden and the benefit of CRT-D versus ICD only for death or nonfatal HF events
      (interaction p = 0.943). In the groups with greatest comorbidity burden (2 and
      >=3), the absolute risk reduction associated with CRT-D over ICD alone appeared
      greater than that seen for groups with less comorbidity burden (0 and 1).
      CONCLUSIONS: During long-term follow-up of MADIT-CRT study patients with LBBB
      randomized to CRT-D, there were differences in HF or death risk and in the degree
      of reverse remodeling among comorbidity groups. However, the burden of
      comorbidity does not appear to compromise the clinical benefits of CRT-D compared
      with ICD alone.

PMID- 28494977
TI  - Aortic Stenosis Is Still Very Tricky, Especially When it Is Moderate.

PMID- 28494976
TI  - Prognostic Implications of Moderate Aortic Stenosis in Patients With Left
      Ventricular Systolic Dysfunction.
AB  - BACKGROUND: Left ventricular (LV) systolic dysfunction and moderate aortic
      stenosis (AS) are more frequent with advancing age and often coexist. Afterload
      reduction is the mainstay of pharmacological treatment of heart failure (HF).
      Aortic valve replacement (AVR) is only formally indicated for symptomatic severe
      AS. OBJECTIVES: This study sought to determine the clinical outcome of patients
      with concomitant moderate AS and LV systolic dysfunction. METHODS:
      Echocardiographic and clinical data of patients with moderate AS and LV systolic
      dysfunction between 2010 and 2015 from 4 large academic institutions were
      retrospectively analyzed. Moderate AS was defined as aortic valve area between
      1.0 and 1.5 cm2 and LV systolic dysfunction defined as LV ejection fraction <50%.
      The primary endpoint was a composite of all-cause death, AVR, and HF
      hospitalization. RESULTS: A total of 305 patients (mean age 73 +/- 11 years; 75%
      male) were included. The majority were symptomatic at the time of index
      echocardiogram (New York Heart Association [NYHA] functional class II: 42%; NYHA
      functional class III: 28%; and NYHA functional class IV: 4%). Ischemic heart
      disease was present in 72% of patients. At 4-year follow-up, the primary
      composite endpoint occurred in 61%. The main predictors for the primary endpoint
      were male sex (p = 0.022), NYHA functional class III or IV (p < 0.001), and peak
      aortic jet velocity (p < 0.001). The rate of the composite of all-cause death or
      HF hospitalization was 48%, rate of all-cause death was 36%, and rate of HF
      hospitalization was 27%. AVR occurred in 24% of patients. CONCLUSIONS: Patients
      with concomitant moderate AS and LV systolic dysfunction are at high risk for
      clinical events. Further studies are needed to determine if earlier AVR in these
      patients might improve clinical outcome.

PMID- 28494978
TI  - Post-Operative Chylothorax in Patients With Congenital Heart Disease.
AB  - BACKGROUND: Post-operative chylothorax in patients with congenital heart disease
      is a challenging problem with substantial morbidity and mortality. Currently, the
      etiology of chylothorax is poorly understood and treatment options are limited.
      OBJECTIVES: This study aimed to report lymphatic imaging findings, determine the
      mechanism of chylothorax after cardiac surgery, and analyze the outcomes of
      lymphatic embolization. METHODS: We conducted a retrospective review of 25
      patients with congenital heart disease and post-operative chylothorax who
      presented for lymphatic imaging and intervention between July 2012 and August
      2016. RESULTS: Based on dynamic contrast-enhanced magnetic resonance
      lymphangiography and intranodal lymphangiography, we identified 3 distinct
      etiologies of chylothorax: 2 patients (8%) with traumatic leak from a thoracic
      duct (TD) branch, 14 patients (56%) with pulmonary lymphatic perfusion syndrome
      (PLPS), and 9 patients (36%) with central lymphatic flow disorder (CLFD), the
      latter defined as abnormal central lymphatic flow, effusions in more than 1
      compartment, and dermal backflow. Patients with traumatic leak and PLPS were
      combined into 1 group of 16 patients without CLFD, of whom 14 (88%) had an intact
      TD. Sixteen patients underwent lymphatic intervention, including complete TD
      embolization. All 16 patients had resolution of chylothorax, with a median of 7.5
      days from intervention to chest tube removal and 15 days from intervention to
      discharge. The 9 patients with CLFD were considered a separate group, of whom 3
      (33%) had an intact TD. Seven patients underwent lymphatic intervention but none
      survived. CONCLUSIONS: Most patients in this study had nontraumatic chylothorax
      and dynamic contrast-enhanced magnetic resonance lymphangiography was essential
      to determine etiology. Lymphatic embolization was successful in patients with
      traumatic leak and PLPS and, thus, should be considered first-line treatment.
      Interventions in patients with CLFD were not successful to resolve chylothorax
      and alternate approaches need to be developed.

PMID- 28494979
TI  - Lymphodynamics in Congenital Heart Disease: The Forgotten Circulation.

PMID- 28494982
TI  - Advocacy for Health Care: All Hands on Deck!

PMID- 28494983
TI  - Chest Pain Unit Network in Germany: Its Effect on Patients With Acute Coronary
      Syndromes.

PMID- 28494981
TI  - Using Predicted Cardiovascular Disease Risk in Conjunction With Blood Pressure to
      Guide Antihypertensive Medication Treatment.
AB  - Using cardiovascular disease (CVD) risk instead of or in addition to blood
      pressure (BP) to guide antihypertensive treatment is an active area of research.
      The purpose of this review is to provide an overview of studies that could inform
      this treatment paradigm. We review data from randomized trials on relative and
      absolute CVD risk reduction that can occur when antihypertensive treatment is
      guided by CVD risk. We also review population-level data on using CVD risk in
      conjunction with BP to guide antihypertensive treatment, the broad distribution
      in CVD risk for people with similar BP levels, and the use of CVD risk for
      guiding antihypertensive treatment among subgroups including older adults, young
      adults, and those with diabetes mellitus or chronic kidney disease. In addition,
      we review potential challenges in implementing antihypertensive treatment
      recommendations that incorporate CVD risk. In closing, we provide recommendations
      for using CVD risk in combination with BP to guide antihypertensive treatment.

PMID- 28494980
TI  - Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure: Current
      Status and Prospects for Further Research.
AB  - More than 1 million heart failure hospitalizations occur annually, and congestion
      is the predominant cause. Rehospitalizations for recurrent congestion portend
      poor outcomes independently of age and renal function. Persistent congestion
      trumps serum creatinine increases in predicting adverse heart failure outcomes.
      No decongestive pharmacological therapy has reduced these harmful consequences.
      Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital
      settings, but with conflicting results regarding safety and efficacy.
      Ultrafiltration performed at fixed rates after onset of therapy-induced increased
      serum creatinine was not superior to standard care and resulted in more
      complications. In contrast, compared with diuretic agents, some data suggest that
      adjustment of ultrafiltration rates to patients' vital signs and renal function
      may be associated with more effective decongestion and fewer heart failure
      events. Essential aspects of ultrafiltration remain poorly defined. Further
      research is urgently needed, given the burden of congestion and data suggesting
      sustained benefits of early and adjustable ultrafiltration.

PMID- 28494984
TI  - Global Cardiovascular Health: A Role for the Interventionalist.

PMID- 28494985
TI  - Role of Acquired Cardiovascular Disease in Tetralogy of Fallot Patients >50 Years
      of Age.

PMID- 28494986
TI  - Truncating Variants in Titin Independently Predict Early Arrhythmias in Patients
      With Dilated Cardiomyopathy.

PMID- 28494987
TI  - Neurocognitive Risk With PCSK9 Inhibitors: Need for More Robust Evidence.

PMID- 28494988
TI  - The Enigma of Left Ventricular Hypertrabeculation: Knowledge About Pregnancies,
      Sports, and Neuromuscular Disorders Is Needed.

PMID- 28494989
TI  - Reply: The Enigma of Left Ventricular Non-Compaction.

PMID- 28494990
TI  - Reply: Mortality and Acute Kidney Injury in Asians With Atrial Fibrillation
      Treated With Dabigatran or Warfarin.

PMID- 28494992
TI  - Correction.

PMID- 28494991
TI  - Mortality and Acute Kidney Injury in Asians With Atrial Fibrillation Treated With
      Dabigatran or Warfarin.

PMID- 28494993
TI  - Robust activation detection methods for real-time and offline fMRI analysis.
AB  - We propose two contributions with novel approaches to fMRI activation analysis.
      The first is to apply confidence intervals to locate activations in real-time,
      and second is a new metric based on robust regression of fMRI signals. These
      contributions are implemented in our four proposed methods; Instantaneous
      Activation Method (IAM), Instantaneous Activation Method with Past Blocks (IAMP)
      for real-time analysis, Task Robust Regression Distance Method (TRRD) for the new
      metric with robust regression and Instantaneous Robust Regression Distance Method
      (IRRD) for both contributions. For comparison, a statistical offline method
      called Task Activation Method (TAM) and a correlation analysis method are also
      implemented. The methods are initially evaluated with synthetic data generated
      using two different approaches; first using varying hemodynamic response function
      signals to simulate a wide range of stimuli responses, along with a Gaussian
      white noise, and second using no activity state data of a real fMRI experiment,
      which removes the need to generate noise. The methods are also tested with real
      fMRI experiments and compared with the results obtained by the widely used SPM
      tool. The results show that instantaneous methods reveal activations that are
      lost statistically in an offline analysis. They also reveal further improvements
      by robust fitting application, which minimizes the outlier effect. TRRD has an
      area under the ROC curve of 0,7127 for very noisy synthetic images, is reaching
      up to 0,9608 as the noise decreases, while the instantaneous score is in the
      range of 0,6124 to 0,8019 in the same noise levels.

PMID- 28494994
TI  - Predicting return visits to the emergency department for pediatric patients:
      Applying supervised learning techniques to the Taiwan National Health Insurance
      Research Database.
AB  - BACKGROUND AND OBJECTIVE: Return visits (RVs) to the emergency department (ED)
      consume medical resources and may represent a patient safety issue. The
      occurrence of unexpected RVs is considered a performance indicator for ED care
      quality. Because children are susceptible to medical errors and utilize
      considerable ED resources, knowing the factors that affect RVs in pediatric
      patients helps improve the quality of pediatric emergency care. METHODS: We
      collected data on visits made by patients aged <=18years to EDs from the National
      Health Insurance Research Database. The outcome of interest was a RV within 3days
      of the initial visit. Potential factors were categorized into demographics,
      medical history, features of ED visits, physician characteristics, hospital
      characteristics, and treatment-seeking behavior. A multivariate logistic
      regression was used to identify independent predictors of RVs. We compared the
      performance of various data mining techniques, including Naive Bayes,
      classification and regression tree (CART), random forest, and logistic
      regression, in predicting RVs. Finally, we developed a decision tree to stratify
      the risk of RVs. RESULTS: Of 125,940 visits, 6,282 (5.0%) were followed by a RV
      within 3 days. Predictors of RVs included younger age, higher acuity, intravenous
      fluid, more examination types, complete blood count, consultation, lower hospital
      level, hospitalization within one week before the initial visit, frequent ED
      visits in the past one year, and visits made in Spring or on Saturdays. Patients
      with allergic diseases and those underwent ultrasound examination were less
      likely to return. Decision tree models performed better in predicting RVs in
      terms of area under curve. The decision tree constructed using the CART technique
      showed that the number of ED visits in the past one year, diagnosis category,
      testing of complete blood count, and age were important discriminators of risk of
      RVs. CONCLUSIONS: We identified several factors which are associated with RVs to
      the ED in pediatric patients. The knowledge of these factors may help assess risk
      of RVs in the ED and guide physicians to reevaluate and provide interventions to
      children belonging to the high risk groups before ED discharge.

PMID- 28494995
TI  - High-accuracy detection of airway obstruction in asthma using machine learning
      algorithms and forced oscillation measurements.
AB  - BACKGROUND AND OBJECTIVES: The main pathologic feature of asthma is episodic
      airway obstruction. This is usually detected by spirometry and body
      plethysmography. These tests, however, require a high degree of collaboration and
      maximal effort on the part of the patient. There is agreement in the literature
      that there is a demand of research into new technologies to improve non-invasive
      testing of lung function. The purpose of this study was to develop automatic
      classifiers to simplify the clinical use and to increase the accuracy of the
      forced oscillation technique (FOT) in the diagnosis of airway obstruction in
      patients with asthma. METHODS: The data consisted of FOT parameters obtained from
      75 volunteers (39 with obstruction and 36 without). Different supervised machine
      learning (ML) techniques were investigated, including k-nearest neighbors (KNN),
      random forest (RF), AdaBoost with decision trees (ADAB) and feature-based
      dissimilarity space classifier (FDSC). RESULTS: The first part of this study
      showed that the best FOT parameter was the resonance frequency (AUC = 0.81),
      which indicates moderate accuracy (0.70-0.90). In the second part of this study,
      the use of the cited ML techniques was investigated. All the classifiers improved
      the diagnostic accuracy. Notably, ADAB and KNN were very close to achieving high
      accuracy (AUC = 0.88 and 0.89, respectively). Experiments including the cross
      products of the FOT parameters showed that all the classifiers improved the
      diagnosis accuracy and KNN was able to reach a higher accuracy range (AUC =
      0.91). CONCLUSIONS: Machine learning classifiers can help in the diagnosis of
      airway obstruction in asthma patients, and they can assist clinicians in airway
      obstruction identification.

PMID- 28494996
TI  - Prediction of labor onset type: Spontaneous vs induced; role of
      electrohysterography?
AB  - BACKGROUND AND OBJECTIVE: Induction of labor (IOL) is a medical procedure used to
      initiate uterine contractions to achieve delivery. IOL entails medical risks and
      has a significant impact on both the mother's and newborn's well-being. The
      assistance provided by an automatic system to help distinguish patients that will
      achieve labor spontaneously from those that will need late-term IOL would help
      clinicians and mothers to take an informed decision about prolonging pregnancy.
      With this aim, we developed and evaluated predictive models using not only
      traditional obstetrical data but also electrophysiological parameters derived
      from the electrohysterogram (EHG). METHODS: EHG recordings were made on singleton
      term pregnancies. A set of 10 temporal and spectral parameters was calculated to
      characterize EHG bursts and a further set of 6 common obstetrical parameters was
      also considered in the predictive models design. Different models were
      implemented based on single layer Support Vector Machines (SVM) and with
      aggregation of majority voting of SVM (double layer), to distinguish between the
      two groups: term spontaneous labor (<=41 weeks of gestation) and IOL late-term
      labor. The areas under the curve (AUC) of the models were compared. RESULTS: The
      obstetrical and EHG parameters of the two groups did not show statistically
      significant differences. The best results of non-contextualized single input
      parameter SVM models were achieved by the Bishop Score (AUC= 0.65) and GA at
      recording time (AUC= 0.68) obstetrical parameters. The EHG parameter median
      frequency, when contextualized with the two obstetrical parameters improved these
      results, reaching AUC= 0.76. Multiple input SVM obtained AUC= 0.70 for all EHG
      parameters. Aggregation of majority voting of SVM models using contextualized EHG
      parameters achieved the best result AUC= 0.93. CONCLUSIONS: Measuring the
      electrophysiological uterine condition by means of electrohysterographic
      recordings yielded a promising clinical decision support system for
      distinguishing patients that will spontaneously achieve active labor before the
      end of full term from those who will require late term IOL. The importance of
      considering these EHG measurements in the patient's individual context was also
      shown by combining EHG parameters with obstetrical parameters. Clinicians
      considering elective labor induction would benefit from this technique.

PMID- 28494997
TI  - Multiple model predictive control for optimal drug administration of mixed
      immunotherapy and chemotherapy of tumours.
AB  - BACKGROUND: Mixed immunotherapy and chemotherapy of tumours is one of the most
      efficient ways to improve cancer treatment strategies. However, it is important
      to 'design' an effective treatment programme which can optimize the ways of
      combining immunotherapy and chemotherapy to diminish their imminent side effects.
      Control engineering techniques could be used for this. METHODS: The method of
      multiple model predictive controller (MMPC) is applied to the modified Stepanova
      model to induce the best combination of drugs scheduling under a better health
      criteria profile. The proposed MMPC is a feedback scheme that can perform global
      optimization for both tumour volume and immune competent cell density by
      performing multiple constraints. RESULTS: Although current studies usually assume
      that immunotherapy has no side effect, this paper presents a new method of mixed
      drug administration by employing MMPC, which implements several constraints for
      chemotherapy and immunotherapy by considering both drug toxicity and autoimmune.
      With designed controller we need maximum 57% and 28% of full dosage of drugs for
      chemotherapy and immunotherapy in some instances, respectively. Therefore,
      through the proposed controller less dosage of drugs are needed, which contribute
      to suitable results with a perceptible reduction in medicine side effects.
      CONCLUSION: It is observed that in the presence of MMPC, the amount of required
      drugs is minimized, while the tumour volume is reduced. The efficiency of the
      presented method has been illustrated through simulations, as the system from an
      initial condition in the malignant region of the state space (macroscopic tumour
      volume) transfers into the benign region (microscopic tumour volume) in which the
      immune system can control tumour growth.

PMID- 28494998
TI  - A novel method for planning liver resections using deformable Bezier surfaces and
      distance maps.
AB  - BACKGROUND AND OBJECTIVE: For more than a decade, computer-assisted surgical
      systems have been helping surgeons to plan liver resections. The most widespread
      strategies to plan liver resections are: drawing traces in individual 2D slices,
      and using a 3D deformable plane. In this work, we propose a novel method which
      requires low level of user interaction while keeping high flexibility to specify
      resections. METHODS: Our method is based on the use of Bezier surfaces, which can
      be deformed using a grid of control points, and distance maps as a base to
      compute and visualize resection margins (indicators of safety) in real-time.
      Projection of resections in 2D slices, as well as computation of resection volume
      statistics are also detailed. RESULTS: The method was evaluated and compared with
      state-of-the-art methods by a group of surgeons (n=5, 5-31 years of experience).
      Our results show that theproposed method presents planning times as low as state
      of-the-art methods (174 s median time) with high reproducibility of results in
      terms of resected volume. In addition, our method not only leads to smooth
      virtual resections easier to perform surgically compared to other state-of-the
      art methods, but also shows superior preservation of resection margins.
      CONCLUSIONS: Our method provides clinicians with a robust and easy-to-use method
      for planning liver resections with high reproducibility, smoothness of resection
      and preservation of resection margin. Our results indicate the ability of the
      method to represent any type of resection and being integrated in real clinical
      work-flows.

PMID- 28494999
TI  - Modeling and control of operator functional state in a unified framework of fuzzy
      inference petri nets.
AB  - BACKGROUND AND OBJECTIVE: In human-machine (HM) hybrid control systems, human
      operator and machine cooperate to achieve the control objectives. To enhance the
      overall HM system performance, the discrete manual control task-load by the
      operator must be dynamically allocated in accordance with continuous-time
      fluctuation of psychophysiological functional status of the operator, so-called
      operator functional state (OFS). The behavior of the HM system is hybrid in
      nature due to the co-existence of discrete task-load (control) variable and
      continuous operator performance (system output) variable. METHODS: Petri net is
      an effective tool for modeling discrete event systems, but for hybrid system
      involving discrete dynamics, generally Petri net model has to be extended.
      Instead of using different tools to represent continuous and discrete components
      of a hybrid system, this paper proposed a method of fuzzy inference Petri nets
      (FIPN) to represent the HM hybrid system comprising a Mamdani-type fuzzy model of
      OFS and a logical switching controller in a unified framework, in which the task
      load level is dynamically reallocated between the operator and machine based on
      the model-predicted OFS. Furthermore, this paper used a multi-model approach to
      predict the operator performance based on three electroencephalographic (EEG)
      input variables (features) via the Wang-Mendel (WM) fuzzy modeling method. The
      membership function parameters of fuzzy OFS model for each experimental
      participant were optimized using artificial bee colony (ABC) evolutionary
      algorithm. Three performance indices, RMSE, MRE, and EPR, were computed to
      evaluate the overall modeling accuracy. RESULTS: Experiment data from six
      participants are analyzed. The results show that the proposed method (FIPN with
      adaptive task allocation) yields lower breakdown rate (from 14.8% to 3.27%) and
      higher human performance (from 90.30% to 91.99%). CONCLUSION: The simulation
      results of the FIPN-based adaptive HM (AHM) system on six experimental
      participants demonstrate that the FIPN framework provides an effective way to
      model and regulate/optimize the OFS in HM hybrid systems composed of continuous
      time OFS model and discrete-event switching controller.

PMID- 28495000
TI  - Prognostic value of tumor volume for patients with advanced lung cancer treated
      with chemotherapy.
AB  - BACKGROUND AND OBJECTIVE: We aim to develop a reference system utilizing computed
      tomography to calculate changes in tumor volume of lung cancer patients after
      chemotherapy to assist physicians in clinical treatment and evaluation. METHODS:
      Image processing techniques were used to analyze the computed tomography of lung
      cancer, locate the tumor, and calculate the tumor volume. The medical indicator
      was then evaluated and analyzed. We examined the correlation between reduced
      tumor volume and survival duration of 88 patients after chemotherapy at Tri
      Service General Hospital, Taiwan. The innovative survival prediction index was
      obtained by four statistical methods: receiver operating characteristic curve,
      Youden index, Kaplan-Meier method, and log rank test. RESULTS: From the image
      processing techniques, tumor volume from each patient were obtained within an
      average of 7.25 seconds. The proposed method was shown to achieve rapid
      positioning of lung tumors and volume reconstruction with an estimation error of
      1.92% when calibrated with an irregularly shaped stone. In medical indicator
      evaluation and analysis, the area below the receiver operating characteristic
      curve is greater than 0.8, indicating good predictability of the medical index
      used herein. The Youden index spotted the best cut-off point of volume, and the
      correlation between the volume's cut-off point and survival time was confirmed
      again by Kaplan-Meier and log rank test. The p-values were all less than 0.05,
      presenting a high degree of correlation between the two, indicating that this
      medical indicator is highly reliable. CONCLUSIONS: The proposed techniques can
      automatically find the location of tumors in the lung, reconstruct the volume,
      and calculate changes in volume before and after treatment, thus obtaining an
      innovative survival prediction index. This will help facilitate early and
      accurate predictions of disease outcomes during the course of therapy, and
      categorize patient stratification into risk groups for more efficient therapies.

PMID- 28495002
TI  - A hybrid energy model for region based curve evolution - Application to CTA
      coronary segmentation.
AB  - BACKGROUND AND OBJECTIVE: State-of-the-art medical imaging techniques have
      enabled non-invasive imaging of the internal organs. However, high volumes of
      imaging data make manual interpretation and delineation of abnormalities
      cumbersome for clinicians. These challenges have driven intensive research into
      efficient medical image segmentation. In this work, we propose a hybrid region
      based energy formulation for effective segmentation in computed tomography
      angiography (CTA) imagery. METHODS: The proposed hybrid energy couples an
      intensity-based local term with an efficient discontinuity-based global model of
      the image for optimal segmentation. The segmentation is achieved using a level
      set formulation due to the computational robustness. After validating the
      statistical significance of the hybrid energy, we applied the proposed model to
      solve an important clinical problem of 3D coronary segmentation. An improved seed
      detection method is used to initialize the level set evolution. Moreover, we
      employed an auto-correction feature that captures the emerging peripheries during
      the curve evolution for completeness of the coronary tree. RESULTS: We evaluated
      the segmentation accuracy of the proposed energy model against the existing
      techniques in two stages. Qualitative and quantitative results demonstrate the
      effectiveness of the proposed framework with a consistent mean sensitivity and
      specificity measures of 80% across the CTA data. Moreover, a high degree of
      agreement with respect to the inter-observer differences justifies the
      generalization of the proposed method. CONCLUSIONS: The proposed method is
      effective to segment the coronary tree from the CTA volume based on hybrid image
      based energy, which can improve the clinicians ability to detect arterial
      abnormalities.

PMID- 28495001
TI  - A comparison between swallowing sounds and vibrations in patients with dysphagia.
AB  - The cervical auscultation refers to the observation and analysis of sounds or
      vibrations captured during swallowing using either a stethoscope or
      acoustic/vibratory detectors. Microphones and accelerometers have recently become
      two common sensors used in modern cervical auscultation methods. There are open
      questions about whether swallowing signals recorded by these two sensors provide
      unique or complementary information about swallowing function; or whether they
      present interchangeable information. This study aims to compare of swallowing
      signals recorded by a microphone and a tri-axial accelerometer from 72 patients
      (mean age 63.94 +/- 12.58 years, 42 male, 30 female), who had videofluoroscopic
      examination. The participants swallowed one or more boluses of thickened liquids
      of different consistencies, including thin liquids, nectar-thick liquids, and
      pudding. A comfortable self-selected volume from a cup or a controlled volume by
      the examiner from a 5 ml spoon was given to the participants. A broad feature set
      was extracted in time, information-theoretic, and frequency domains from each of
      881 swallows presented in this study. The swallowing sounds exhibited
      significantly higher frequency content and kurtosis values than the swallowing
      vibrations. In addition, the Lempel-Ziv complexity was lower for swallowing
      sounds than those for swallowing vibrations. To conclude, information provided by
      microphones and accelerometers about swallowing function are unique and these two
      transducers are not interchangeable. Consequently, the selection of transducer
      would be a vital step in future studies.

PMID- 28495003
TI  - Viral warts (Human Papilloma Virus) as a potential risk for breast cancer among
      younger females.
AB  - INTRODUCTION: There have been several reports on the role of human papillomavirus
      (HPV) in the etiology of breast cancer. To our knowledge, this is first study to
      use disease-disease association data-mining approach to analyzing viral warts and
      breast cancer to be conducted in Taiwanese population. MATERIALS AND METHODS: We
      analyzed the Taiwan's National Health Insurance database (NHIDM data comprising
      of 23 million patient data) to examine the association between viral warts and
      female breast carcinoma. The patients were categorized into three groups: breast
      cancer only, viral warts only, and those with both breast cancer and viral warts.
      The Cox proportion hazard regression analysis was used to measure the effect of
      HPV on the time to breast cancer diagnosis. Multivariable analyzes and stratified
      analyzes using hazard ratios (HRs) were presented with 95% confidence intervals
      (CIs) after adjusting for age, and CCI. RESULT: Among 807,578 HPV population, we
      identified 6014 breast cancer cases. The HPV group was associated with a
      significantly higher risk of developing breast cancer (HR, 1.18; 95% CI, 1.15
      1.21; p< 0.001) compared with the non-HPV group. HPV patients with age group 18
      39 was slightly higher risk of breast cancer occurrence (HR, 1.07; 95% CI, 1.01
      1.13; p<.05). The risk of breast cancer in 10-year incidence was 7% higher for
      females less than 40 years and 23% for over 40 year's patients when compared with
      non-HPV patients of the same age group. CONCLUSION: Our study indicates that
      women who develop viral warts are at a significantly higher risk of developing
      breast cancer than women who have not diagnosed with viral warts. Thus, the
      presence of viral warts is a potential risk to breast cancer. Therefore, we
      suggest patients diagnosed with viral warts may get early screening for breast
      cancer.

PMID- 28495004
TI  - Optimized PID control of depth of hypnosis in anesthesia.
AB  - BACKGROUND AND OBJECTIVE: This paper addresses the use of proportional-integral
      derivative controllers for regulating the depth of hypnosis in anesthesia by
      using propofol administration and the bispectral index as a controlled variable.
      In fact, introducing an automatic control system might provide significant
      benefits for the patient in reducing the risk for under- and over-dosing.
      METHODS: In this study, the controller parameters are obtained through genetic
      algorithms by solving a min-max optimization problem. A set of 12 patient models
      representative of a large population variance is used to test controller
      robustness. The worst-case performance in the considered population is minimized
      considering two different scenarios: the induction case and the maintenance case.
      RESULTS: Our results indicate that including a gain scheduling strategy enables
      optimal performance for induction and maintenance phases, separately. Using a
      single tuning to address both tasks may results in a loss of performance up to
      102% in the induction phase and up to 31% in the maintenance phase. Further on,
      it is shown that a suitably designed low-pass filter on the controller output can
      handle the trade-off between the performance and the noise effect in the control
      variable. CONCLUSIONS: Optimally tuned PID controllers provide a fast induction
      time with an acceptable overshoot and a satisfactory disturbance rejection
      performance during maintenance. These features make them a very good tool for
      comparison when other control algorithms are developed.

PMID- 28495005
TI  - Developing a ubiquitous health management system with healthy diet control for
      metabolic syndrome healthcare in Taiwan.
AB  - BACKGROUND AND OBJECTIVE: Self-management in healthcare can allow patients
      managing their health data anytime and everywhere for prevention of chronic
      diseases. This study established a prototype of ubiquitous health management
      system (UHMS) with healthy diet control (HDC) for people who need services of
      metabolic syndrome healthcare in Taiwan. METHODS: System infrastructure comprises
      of three portals and a database tier with mutually supportive components to
      achieve functionality of diet diaries, nutrition guides, and health risk
      assessments for self-health management. With the diet, nutrition, and personal
      health database, the design enables the analytical diagrams on the interactive
      interface to support a mobile application for diet diary, a Web-based platform
      for health management, and the modules of research and development for medical
      care. For database integrity, dietary data can be stored at offline mode prior to
      transformation between mobile device and server site at online mode. RESULTS: The
      UHMS-HDC was developed by open source technology for ubiquitous health management
      with personalized dietary criteria. The system integrates mobile, internet, and
      electronic healthcare services with the diet diary functions to manage healthy
      diet behaviors of users. The virtual patients were involved to simulate the self
      health management procedure. The assessment functions were approved by capturing
      the screen snapshots in the procedure. The proposed system development was
      capable for practical intervention. CONCLUSION: This approach details the
      expandable framework with collaborative components regarding the self-developed
      UHMS-HDC. The multi-disciplinary applications for self-health management can
      support the healthcare professionals to reduce medical resources and improve
      healthcare effects for the patient who requires monitoring personal health
      condition with diet control. The proposed system can be practiced for
      intervention in the hospital.

PMID- 28495006
TI  - E-health internationalization requirements for audit purposes.
AB  - BACKGROUND AND OBJECTIVE: In the 21st century, e-health is proving to be one of
      the strongest drivers for the global transformation of the health care industry.
      Health information is currently truly ubiquitous and widespread, but in order to
      guarantee that everyone can appropriately access and understand this information,
      regardless of their origin, it is essential to bridge the international gap. The
      diversity of health information seekers languages and cultures signifies that e
      health applications must be adapted to satisfy their needs. METHODS: In order to
      achieve this objective, current and future e-health programs should take into
      account the internationalization aspects. This paper presents an
      internationalization requirements specification in the form of a reusable
      requirements catalog, obtained from the principal related standards, and
      describes the key methodological elements needed to perform an e-health software
      audit by using the internationalization knowledge previously gathered. RESULTS: S
      Health, a relevant, well-known Android application that has more than 150 million
      users in over 130 countries, was selected as a target for the e-health
      internationalization audit method and requirements specification presented above.
      This application example helped us to put into practice the proposal and show
      that the procedure is realistic and effective. CONCLUSIONS: The approach
      presented in this study is subject to continuous improvement through the
      incorporation of new knowledge originating from additional information sources,
      such as other standards or stakeholders. The application example is useful for
      early evaluation and serves to assess the applicability of the
      internationalization catalog and audit methodology, and to improve them. It would
      be advisable to develop of an automated tool with which to carry out the audit
      method.

PMID- 28495007
TI  - A lightweight QRS detector for single lead ECG signals using a max-min difference
      algorithm.
AB  - BACKGROUND AND OBJECTIVES: Detection of the R-peak pertaining to the QRS complex
      of an ECG signal plays an important role for the diagnosis of a patient's heart
      condition. To accurately identify the QRS locations from the acquired raw ECG
      signals, we need to handle a number of challenges, which include noise, baseline
      wander, varying peak amplitudes, and signal abnormality. This research aims to
      address these challenges by developing an efficient lightweight algorithm for QRS
      (i.e., R-peak) detection from raw ECG signals. METHODS: A lightweight real-time
      sliding window-based Max-Min Difference (MMD) algorithm for QRS detection from
      Lead II ECG signals is proposed. Targeting to achieve the best trade-off between
      computational efficiency and detection accuracy, the proposed algorithm consists
      of five key steps for QRS detection, namely, baseline correction, MMD curve
      generation, dynamic threshold computation, R-peak detection, and error
      correction. Five annotated databases from Physionet are used for evaluating the
      proposed algorithm in R-peak detection. Integrated with a feature extraction
      technique and a neural network classifier, the proposed ORS detection algorithm
      has also been extended to undertake normal and abnormal heartbeat detection from
      ECG signals. RESULTS: The proposed algorithm exhibits a high degree of robustness
      in QRS detection and achieves an average sensitivity of 99.62% and an average
      positive predictivity of 99.67%. Its performance compares favorably with those
      from the existing state-of-the-art models reported in the literature. In regards
      to normal and abnormal heartbeat detection, the proposed QRS detection algorithm
      in combination with the feature extraction technique and neural network
      classifier achieves an overall accuracy rate of 93.44% based on an empirical
      evaluation using the MIT-BIH Arrhythmia data set with 10-fold cross validation.
      CONCLUSIONS: In comparison with other related studies, the proposed algorithm
      offers a lightweight adaptive alternative for R-peak detection with good
      computational efficiency. The empirical results indicate that it not only yields
      a high accuracy rate in QRS detection, but also exhibits efficient computational
      complexity at the order of O(n), where n is the length of an ECG signal.

PMID- 28495008
TI  - A fully automatic approach for multimodal PET and MR image segmentation in gamma
      knife treatment planning.
AB  - BACKGROUND AND OBJECTIVES: Nowadays, clinical practice in Gamma Knife treatments
      is generally based on MRI anatomical information alone. However, the joint use of
      MRI and PET images can be useful for considering both anatomical and metabolic
      information about the lesion to be treated. In this paper we present a co
      segmentation method to integrate the segmented Biological Target Volume (BTV),
      using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target
      Volume (GTV), on the respective co-registered MR images. The resulting volume
      gives enhanced brain tumor information to be used in stereotactic neuro
      radiosurgery treatment planning. GTV often does not match entirely with BTV,
      which provides metabolic information about brain lesions. For this reason, PET
      imaging is valuable and it could be used to provide complementary information
      useful for treatment planning. In this way, BTV can be used to modify GTV,
      enhancing Clinical Target Volume (CTV) delineation. METHODS: A novel fully
      automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife(r)
      treatments is proposed. This approach improves and combines two computer-assisted
      and operator-independent single modality methods, previously developed and
      validated, to segment BTV and GTV from PET and MR images, respectively. In
      addition, the GTV is utilized to combine the superior contrast of PET images with
      the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total
      of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were
      retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI
      segmentation is also presented. Overlap-based and spatial distance-based metrics
      were considered to quantify similarity concerning PET and MRI segmentation
      approaches. Statistics was also included to measure correlation among the
      different segmentation processes. Since it is not possible to define a gold
      standard CTV according to both MRI and PET images without treatment response
      assessment, the feasibility and the clinical value of BTV integration in Gamma
      Knife treatment planning were considered. Therefore, a qualitative evaluation was
      carried out by three experienced clinicians. RESULTS: The achieved experimental
      results showed that GTV and BTV segmentations are statistically correlated
      (Spearman's rank correlation coefficient: 0.898) but they have low similarity
      degree (average Dice Similarity Coefficient: 61.87 +/- 14.64). Therefore, volume
      measurements as well as evaluation metrics values demonstrated that MRI and PET
      convey different but complementary imaging information. GTV and BTV could be
      combined to enhance treatment planning. In more than 50% of cases the CTV was
      strongly or moderately conditioned by metabolic imaging. Especially, BTVMRI
      enhanced the CTV more accurately than BTV in 25% of cases. CONCLUSIONS: The
      proposed fully automatic multimodal PET/MRI segmentation method is a valid
      operator-independent methodology helping the clinicians to define a CTV that
      includes both metabolic and morphologic information. BTVMRI and GTV should be
      considered for a comprehensive treatment planning.

PMID- 28495010
TI  - Predictive Analytics through Machine Learning in the clinical settings.

PMID- 28495009
TI  - A two-step convolutional neural network based computer-aided detection scheme for
      automatically segmenting adipose tissue volume depicting on CT images.
AB  - Accurately assessment of adipose tissue volume inside a human body plays an
      important role in predicting disease or cancer risk, diagnosis and prognosis. In
      order to overcome limitation of using only one subjectively selected CT image
      slice to estimate size of fat areas, this study aims to develop and test a
      computer-aided detection (CAD) scheme based on deep learning technique to
      automatically segment subcutaneous fat areas (SFA) and visceral fat areas (VFA)
      depicting on volumetric CT images. A retrospectively collected CT image dataset
      was divided into two independent training and testing groups. The proposed CAD
      framework consisted of two steps with two convolution neural networks (CNNs)
      namely, Selection-CNN and Segmentation-CNN. The first CNN was trained using 2,240
      CT slices to select abdominal CT slices depicting SFA and VFA. The second CNN was
      trained with 84,000pixel patches and applied to the selected CT slices to
      identify fat-related pixels and assign them into SFA and VFA classes. Comparing
      to the manual CT slice selection and fat pixel segmentation results, the accuracy
      of CT slice selection using the Selection-CNN yielded 95.8%, while the accuracy
      of fat pixel segmentation using the Segmentation-CNN was 96.8%. This study
      demonstrated the feasibility of applying a new deep learning based CAD scheme to
      automatically recognize abdominal section of human body from CT scans and segment
      SFA and VFA from volumetric CT data with high accuracy or agreement with the
      manual segmentation results.

PMID- 28495011
TI  - Solitary fibrous tumour of pleura: CT differentiation of benign and malignant
      types.
AB  - AIM: To analyse and compare the computed tomography (CT) features of benign and
      malignant types of histopathologically proven cases of solitary fibrous tumours
      of pleura (SFTP). MATERIALS AND METHODS: Retrospective analysis of preoperative
      CT images of 28 cases of histopathologically proven and classified SFTP from
      three participating institutions was performed. Patient demographics and lesion
      characteristics including size, borders, presence of a pedicle, extension into
      the fissure, attenuation, enhancement, pleural effusion, and calcifications were
      recorded and correlated with the final histopathological diagnosis. Type and
      results of preoperative biopsy were also recorded. Follow-up imaging and the
      clinical charts were reviewed to identify recurrence. RESULTS: Out of 28 cases
      (15 women and 13 men), 18 were proven to be benign and 10 were malignant. The
      mean age of patients was 58.1+/-15.9 and 66.5+/-11.8 years (p=0.1564) for benign
      and malignant tumours, respectively. The median (interquartile range) diameter
      was 6.05 (3.2-10.9) cm for benign and 15.7 (7.1-17.5) cm for malignant type
      tumours (p=0.0291). Tumours had lobulate borders in 28% (5/18) of benign cases
      and in 80% (8/10) of malignant cases (p=0.0163). Extension into adjacent fissure
      was seen in 22% (4/18) of benign lesions and 40% (4/10) of malignant lesions
      (p=0.40). A pedicle was present in 17% (3/18) of benign and 10% (1/10) of
      malignant lesions (p=1). Heterogeneous attenuation was present in 61% (11/18) of
      benign and 90% (9/10) of malignant lesions (p=0.19). Calcification was present in
      17% (3/18) of benign tumours and in 70% (7/10) of malignant tumours (p=0.0113).
      Pleural effusion was present in 6% (1/18) of benign and 40% (4/10) of malignant
      lesions (p=0.04). Only 1/13 preoperative fine-needle aspirates yielded diagnosis
      of SFTP. Preoperative diagnosis of SFTP was made in all cases (11/11) with core
      biopsies. At follow-up (1-10 years, mean 3 years), local recurrence occurred in
      3/6 (50%) patients with malignant SFTP and in none of the 10 patients with benign
      SFTP. CONCLUSION: No definite imaging feature to differentiate benign from
      malignant SFTP was found. Large size, lobulate borders, presence of
      calcification, and ipsilateral pleural effusion were the only CT features
      predictive of malignancy. In suspected cases, core biopsies should be performed
      rather than fine-needle aspiration.

PMID- 28495012
TI  - What do clinicians treat: Diagnoses or symptoms? The incremental validity of a
      symptom-based, dimensional characterization of emotional disorders in predicting
      medication prescription patterns.
AB  - BACKGROUND: Although practice guidelines are based on disorders specified in
      diagnostic manuals, such as the DSM, practitioners appear to follow symptoms when
      making treatment decisions. Psychiatric medication is generally prescribed in a
      transdiagnostic manner, further highlighting how symptoms, not diagnoses, often
      guide clinical practice. A quantitative approach to nosology promises to provide
      better guidance as it describes psychopathology dimensionally and its
      organization reflects patterns of covariation among symptoms. AIM: To investigate
      whether a quantitative classification of emotional disorders can account for
      naturalistic medication prescription patterns better than traditional diagnoses.
      METHODS: Symptom dimensions and DSM diagnoses of emotional disorders, as well as
      prescribed medications, were assessed using interviews in a psychiatric
      outpatient sample (N=318, mean age 42.5years old, 59% female, 81% Caucasian).
      RESULTS: Each diagnosis was associated with prescription of multiple medication
      classes, and most medications were associated with multiple disorders. This was
      largely due to heterogeneity of clinical diagnoses, with narrow, homogenous
      dimensions underpinning diagnoses showing different medication profiles. Symptom
      dimensions predicted medication prescription better than DSM diagnoses,
      irrespective of whether this was examined broadly across all conditions, or
      focused on a specific disorder and medication indicated for it. CONCLUSIONS:
      Psychiatric medication was prescribed in line with symptoms rather than DSM
      diagnoses. A quantitative approach to nosology may better reflect treatment
      planning and be a more effective guide to pharmacotherapy than traditional
      diagnoses. This adds to a diverse body of evidence about superiority of the
      quantitative system in practical applications and highlights its potential to
      improve psychiatric care.

PMID- 28495014
TI  - Bisphosphonates or denosumab discontinuation and risk of fractures.

PMID- 28495013
TI  - The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to
      Classifying Acute Pain Conditions.
AB  - OBJECTIVE: With the increasing societal awareness of the prevalence and impact of
      acute pain, there is a need to develop an acute pain classification system that
      both reflects contemporary mechanistic insights and helps guide future research
      and treatment. Existing classifications of acute pain conditions are limiting,
      with a predominant focus on the sensory experience (eg, pain intensity) and
      pharmacologic consumption. Consequently, there is a need to more broadly
      characterize and classify the multidimensional experience of acute pain. SETTING:
      Consensus report following expert panel involving the Analgesic, Anesthetic, and
      Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks
      (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine
      (AAPM). METHODS: As a complement to a taxonomy recently developed for chronic
      pain, the ACTTION public-private partnership with the US Food and Drug
      Administration, the APS, and the AAPM convened a consensus meeting of experts to
      develop an acute pain taxonomy using prevailing evidence. Key issues pertaining
      to the distinct nature of acute pain are presented followed by the agreed-upon
      taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following
      dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4)
      impact/functional consequences, and 5) putative pathophysiologic pain mechanisms.
      Future efforts will consist of working groups utilizing this taxonomy to develop
      diagnostic criteria for a comprehensive set of acute pain conditions.
      PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a
      multidimensional acute pain classification system designed to classify acute pain
      along the following dimensions: 1) core criteria, 2) common features, 3)
      modulating factors, 4) impact/functional consequences, and 5) putative
      pathophysiologic pain mechanisms. CONCLUSIONS: Significant numbers of patients
      still suffer from significant acute pain, despite the advent of modern multimodal
      analgesic strategies. Mismanaged acute pain has a broad societal impact as
      significant numbers of patients may progress to suffer from chronic pain. An
      acute pain taxonomy provides a much-needed standardization of clinical diagnostic
      criteria, which benefits clinical care, research, education, and public policy.
      For the purposes of the present taxonomy, acute pain is considered to last up to
      seven days, with prolongation to 30 days being common. The current understanding
      of acute pain mechanisms poorly differentiates between acute and chronic pain and
      is often insufficient to distinguish among many types of acute pain conditions.
      Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook
      a similar approach to organizing various acute pain conditions.

PMID- 28495015
TI  - Erratum to 'Pleiotropic protective effects of vitamin D against high fat diet
      induced metabolic syndrome in rats: One for all' [Eur. J. Pharmacol. 792 (2016)
      38-47].

PMID- 28495016
TI  - Corrigendum to "Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate
      exhibits antihypertensive activity in rats through increase in intracellular cGMP
      level and blockade of calcium channels" [Eur. J. Pharmacol. 799 (2017) 84-93].

PMID- 28495017
TI  - Graphene for the development of the next-generation of biocomposites for dental
      and medical applications.
AB  - OBJECTIVE: Graphene and its derivatives, graphene oxide (GO) and reduced graphene
      oxide (rGO), are 2D carbon-based materials with remarkable physical, chemical and
      biological properties. Graphene sheets have high specific surface area and
      mechanical strength. Moreover, they have been shown to influence the
      differentiation of stem cells and to improve properties of biomaterials. METHODS:
      Here, we present the recent achievements on the use of graphene and its
      derivatives to improve properties and enhance bioactivity of biomaterials. We
      also discuss the biosafety constraints to be solved to translate these
      carbonaceous materials to the clinic. RESULTS: Graphene and its derivatives can
      be functionalized and further modified with several bioactive molecules. They can
      be combined with several biomaterials used in regenerative and reconstructive
      dentistry and medicine. The resultant graphene-modified composites often present
      improved physico-mechanical properties and enhanced bioactivity. Moreover,
      graphene-modified composites are promising candidates to deliver growth factors,
      drugs and others bioactive compounds. SIGNIFICANCE: Graphene can improve the
      physical, chemical and mechanical properties of biomaterials. As it can be
      functionalized and combined with several biomolecules, graphene holds enormous
      potential to be used as drug carriers or substrates and scaffolds for cell-based
      tissue engineering strategies.

PMID- 28495018
TI  - Effects of leptin administration on development, vascularization and function of
      Corpus luteum in alpacas submitted to pre-ovulatory fasting.
AB  - The objective of this study was to determine the effect of leptin administration
      on the development, vascularization and function of Corpus luteum (CL) in alpacas
      submitted to pre-ovulatory fasting. Fourteen alpacas were kept in fasting
      conditions for 72h and received five doses of o-leptin (2MUg/kg e.v.; Leptin
      group) or saline (Control group) every 12h. Ovulation was induced with a GnRH
      dose (Day 0). The ovaries were examined every other day by trans-rectal
      ultrasonography (7.5MHz; mode B and power Doppler) from Day 0 to 13 to determine
      the pre-ovulatory follicle diameter and ovulation, and then to monitor CL
      diameter and vascularization until the regression phase. Serial blood samples
      were taken after GnRH treatment to determine plasma LH concentration; and every
      other day from Days 1 to 13 to determine plasma progesterone and leptin
      concentrations. The pre-ovulatory follicle and CL diameter, LH, progesterone and
      leptin plasma concentrations were not affected by treatment (P>0.05). The
      vascularization area of the CL was, nevertheless, affected by the treatment
      (P<0.01) with significant differences between groups at Days 3, 7 and 9 (P<0.05).
      The Leptin group had a larger maximum vascularization area (0.67+/-0.1 compared
      with 0.35+/-0.1cm2; P<0.05). In addition, there was a positive correlation
      between CL vascularization, CL diameter and plasma progesterone. The exogenous
      administration of leptin during pre-ovulatory fasting increased the
      vascularization of the CL in alpacas in vivo.

PMID- 28495019
TI  - Response to letter: Psychometric properties of the Tinnitus Functional Index
      (TFI): Assessment in a UK research volunteer population.

PMID- 28495020
TI  - UPLC-MS/MS method for determination of sofosbuvir in human plasma.
AB  - INTRODUCTION: A sensitive and rapid method for quantitation of Sofosbuvir in
      human plasma has been established using ultra performance liquid chromatography
      electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). MATERIALS AND
      METHODS: Sofosbuvir d3 was used as an internal standard. Sofosbuvir and internal
      standard in plasma sample were extracted using ethyl acetate (liquid liquid
      extraction). A centrifuged upper layer was then evaporated and reconstituted with
      the mobile phase of 0.5% formic acid: methanol (30:70, v/v). The reconstituted
      samples were injected into a Gemini C18 (50*4.6mm, 5MUm) column. RESULTS: Using
      MS/MS in the multiple reaction monitoring mode, Sofosbuvir and Sofosbuvir d3 were
      detected without severe interferences from human plasma matrix. Sofosbuvir
      produced a protonated precursor ion ([M+H]+) at m/z 428.35 and a corresponding
      product ion at m/z 279.26. The internal standard produced a protonated precursor
      ion ([M+H]+) at m/z 431.38 and a corresponding product ion at m/z 282.37. The
      calibration curves for the analyte was linear (R2>=0.9956, n=4) over the
      concentration range of 4.063-8000.010ng/mL. Stability studies revealed that
      Sofosbuvir was stable in plasma during bench top (7h at room temperature), in
      injector (20h), at the end of five successive freeze and thaw cycles and long
      term at -70 degrees C+/-15 degrees C for 15 days. CONCLUSION: The developed
      method was validated as per the guidelines of USFDA and the obtained results were
      found to be within the limits and could be successfully employed for the
      determination of Sofosbuvir in human plasma for regular and pharmacokinetic
      studies.

PMID- 28495021
TI  - Damage control and intramedullary nailing for long bone fractures in polytrauma
      patients.
AB  - The early fracture treatment in patients with multiple injuries should be focused
      on damage control. The fracture type and its location, local soft tissue
      condition as well as the patient's physiological condition shall determine the
      time and type of fracture treatment. Prevention of local and systemic
      complications must be immediately considered and included in the treatment
      planning. The use of external fixator (ExFix), which will be replaced by IM
      implants in most cases at a later stage, provides adequate temporary fracture
      stabilization with less collateral damage. Good clinical results can be expected
      in patients with long bone fractures if the principles of damage control surgery
      are applied and local complications are prevented through proper reduction, firm
      fixation, early soft tissue reconstruction, and early rehabilitation.

PMID- 28495023
TI  - Reduction of SPECT MPI Radiation Dose Using Contemporary Protocols and
      Technology.

PMID- 28495022
TI  - Delineating the joint hierarchical structure of clinical and personality
      disorders in an outpatient psychiatric sample.
AB  - BACKGROUND: A large body of research has focused on identifying the optimal
      number of dimensions - or spectra - to model individual differences in
      psychopathology. Recently, it has become increasingly clear that ostensibly
      competing models with varying numbers of spectra can be synthesized in
      empirically derived hierarchical structures. METHODS AND MATERIALS: We examined
      the convergence between top-down (bass-ackwards or sequential principal
      components analysis) and bottom-up (hierarchical agglomerative cluster analysis)
      statistical methods for elucidating hierarchies to explicate the joint
      hierarchical structure of clinical and personality disorders. Analyses examined
      24 clinical and personality disorders based on semi-structured clinical
      interviews in an outpatient psychiatric sample (n=2900). RESULTS: The two methods
      of hierarchical analysis converged on a three-tier joint hierarchy of
      psychopathology. At the lowest tier, there were seven spectra - disinhibition,
      antagonism, core thought disorder, detachment, core internalizing, somatoform,
      and compulsivity - that emerged in both methods. These spectra were nested under
      the same three higher-order superspectra in both methods: externalizing, broad
      thought dysfunction, and broad internalizing. In turn, these three superspectra
      were nested under a single general psychopathology spectrum, which represented
      the top tier of the hierarchical structure. CONCLUSIONS: The hierarchical
      structure mirrors and extends upon past research, with the inclusion of a novel
      compulsivity spectrum, and the finding that psychopathology is organized in three
      superordinate domains. This hierarchy can thus be used as a flexible and
      integrative framework to facilitate psychopathology research with varying levels
      of specificity (i.e., focusing on the optimal level of detailed information,
      rather than the optimal number of factors).

PMID- 28495024
TI  - Live-Cell Nanoscopy in Antiadhesion Therapy.
AB  - Live-cell nanoscopy has contributed significantly to assessing the inhibition of
      adhesion of uropathogenic Escherichia coli and Staphylococcus aureus by
      glycoconjugates and monoclonal antibodies, respectively, and of S. aureus surface
      attachment and cell-cell association by a synthetic peptide. This new technology
      shows promise for the development of antiadhesion therapies against bacterial
      pathogens.

PMID- 28495025
TI  - The cognitive neuroscience of source memory: Moving the ball forward.

PMID- 28495026
TI  - Neck-Related Physical Function, Self-Efficacy, and Coping Strategies in Patients
      With Cervical Radiculopathy: A Randomized Clinical Trial of Postoperative
      Physiotherapy.
AB  - OBJECTIVE: The purpose of this study was to compare postoperative rehabilitation
      with structured physiotherapy to the standard approach in patients with cervical
      radiculopathy (CR) in a prospective randomized study at 6 months follow-up based
      on measures of neck-related physical function, self-efficacy, and coping
      strategies. METHODS: Patients with persistent CR and scheduled for surgery (N =
      202) were randomly assigned to structured postoperative physiotherapy or a
      standard postoperative approach. Structured postoperative physiotherapy combined
      neck-specific exercises with a behavioral approach. Baseline, 3-month, and 6
      month evaluations included questionnaires and clinical examinations. Neck muscle
      endurance, active cervical range of motion, self-efficacy, pain catastrophizing
      (CSQ-CAT), perceived control over pain, and ability to decrease pain were
      analyzed for between-group differences using complete case and per-protocol
      approaches. RESULTS: No between-group difference was reported at the 6-month
      follow-up (P = .05-.99), but all outcomes had improved from baseline (P < .001).
      Patients undergoing structured postoperative physiotherapy with >=50% attendance
      at treatment sessions had larger improvements in CSQ-CAT (P = .04) during the
      rehabilitation period from 3 to 6 months after surgery compared with the patients
      who received standard postoperative approach. CONCLUSIONS: No between-group
      difference was found at 6 months after surgery based on measures of neck-related
      physical function, self-efficacy, and coping strategies. However, the results
      confirm that neck-specific exercises are tolerated by patients with CR after
      surgery and may suggest a benefit from combining surgery with structured
      postoperative physiotherapy for patients with CR.

PMID- 28495027
TI  - Medial Femoral Condyle Microvascular Bone Transfer as a Treatment for Capitate
      Avascular Necrosis: Surgical Technique and Case Report.
AB  - : Avascular necrosis (AVN) of the capitate is a rare clinical entity for which a
      variety of treatment options have been described, ranging from immobilization to
      microvascular bone transfer. Outcomes following medial femoral condyle
      corticocancellous free flap reconstruction have not been reported for this
      specific pathology. We present the case of a 16-year-old girl with posttraumatic
      capitate AVN who was treated with curettage and medial femoral condyle
      corticocancellous vascularized bone grafting. At 18 months after surgery, the
      patient remains pain-free and had resumed all activities including lifeguarding
      by 6 months after surgery. This microsurgical technique, described previously for
      AVN of the scaphoid and lunate, may be applied in a similar fashion for the
      capitate with promising clinical results. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic V.

PMID- 28495028
TI  - Real-world Clinical Outcomes Among Patients With Type 2 Diabetes Receiving
      Canagliflozin at a Specialty Diabetes Clinic: Subgroup Analysis by Baseline HbA1c
      and Age.
AB  - PURPOSE: Canagliflozin, a sodium glucose co-transporter 2 inhibitor developed for
      the treatment of type 2 diabetes mellitus (T2DM), has demonstrated effectiveness
      in patients with T2DM receiving care at a specialty diabetes clinic. We report
      the outcomes in these patients in subgroups classified by baseline hemoglobin A1c
      (HbA1c) and age. METHODS: This subgroup analysis was based on a review of data
      from the electronic health records of adults with T2DM who were prescribed
      canagliflozin at a specialty diabetes clinic and who returned for >=1 follow-up
      office visit. Mean changes from baseline to the first and second follow-up office
      visits in HbA1c, body weight, and systolic and diastolic blood pressure (BP) were
      calculated in each subgroup classified by baseline HbA1c (>=7.0%, >=8.0%, and
      >9.0%) and age (<65 and >=65 years). FINDINGS: Of the 462 patients included in
      the study, 430, 305, and 169 patients had baseline HbA1c >=7.0%, >=8.0%, and
      >9.0%, respectively; 396 and 66 patients were aged <65 and >=65 years,
      respectively. With canagliflozin use, patients across subgroups classified by
      baseline HbA1c and age experienced clinically and statistically significant
      reductions from baseline in HbA1c, body weight, and systolic BP that were
      sustained over 2 office visits; diastolic BP was also reduced across baseline
      HbA1c and age subgroups. Greater reductions in HbA1c were seen among the
      canagliflozin-treated patients with higher baseline HbA1c and among younger
      versus older patients. IMPLICATION: These findings from clinical practice
      demonstrate real-world effectiveness of canagliflozin in lowering HbA1c, body
      weight, and systolic BP among patients with T2DM, regardless of baseline HbA1c
      levels or age.

PMID- 28495029
TI  - The Pharmacokinetics of the CYP3A Substrate Midazolam After Steady-state Dosing
      of Delafloxacin.
AB  - PURPOSE: Delafloxacin is a novel anionic fluoroquinolone in Phase III development
      for the treatment of serious skin infections. The objective of this study was to
      evaluate the effects of delafloxacin on the pharmacokinetics of midazolam, a
      cytochrome P450 (CYP) 3A substrate. METHODS: CYP3A activity using midazolam as a
      probe was assessed before and after multiple doses of delafloxacin to reach
      steady state. In this nonrandomized, open-label, single-sequence, Phase I study,
      22 healthy male and female subjects were administered a single 5-mg oral dose of
      midazolam on days 1 and 8, with oral delafloxacin 450 mg every 12 hours
      administered from days 3 to 8. Full pharmacokinetic profiles were obtained on
      days 1 and 8 (midazolam and 1-hydroxymidazolam) and days 3 and 7 (delafloxacin).
      FINDINGS: The geometric mean ratios (90% CIs) for AUC0-infinity and Cmax of
      midazolam coadministered with delafloxacin versus midazolam alone were 89.4 (83.2
      96.0) and 93.6 (83.7-104.6). Similarly, the geometric ratio for the AUC0-infinity
      of 1-hydroxymidazolam, the primary metabolite of midazolam, was 105.7 (97.7
      114.3); the ratio of Cmax was not equivalent at 116.1 (101.7-132.4), which was
      outside the CI of 80% to 125%. Multiple doses of oral delafloxacin for 6 days
      were generally well tolerated. IMPLICATIONS: Steady-state dosing of delafloxacin
      produced no significant changes in midazolam pharmacokinetics, except for a small
      but not clinically relevant change in the Cmax of 1-hydroxymidazolam.
      ClinicalTrials.gov identifier: NCT02505997.

PMID- 28495030
TI  - Intubation and salicylate overdose.

PMID- 28495031
TI  - A pilot mobile integrated healthcare program for frequent utilizers of emergency
      department services.
AB  - PURPOSE: To examine whether or not a mobile integrated health (MIH) program may
      improve health-related quality of life while reducing emergency department (ED)
      transports, ED admissions, and inpatient hospital admissions in frequent
      utilizers of ED services. METHODS: A small retrospective evaluation assessing pre
      and post-program quality of life, ED transports, ED admissions, and inpatient
      hospital admissions was conducted in patients who frequently used the ED for non
      emergent or emergent/primary care treatable conditions. RESULTS: Pre- and post
      program data available on 64 program completers are reported. Of those with
      mobility problems (n=42), 38% improved; those with problems performing usual
      activities (N=45), 58% reported improvement; and of those experiencing moderate
      to extreme pain or discomfort (N=48), 42% reported no pain or discomfort after
      program completion. Frequency of ED transports decreased (5.34+/-6.0 vs. 2.08+/
      3.3; p <0.000), as did ED admissions (9.66+/-10.2 vs. 3.30+/-4.6; p<0.000), and
      inpatient hospital admissions (3.11+/-5.5 vs. 1.38+/-2.5; p=0.003). CONCLUSION:
      Results suggest that MIH participation is associated with improved quality of
      life, reduced ED transports, ED admissions, and inpatient hospital admissions.
      The MIH program may have potential to improve health outcomes in patients who are
      frequent ED users for non-emergent or emergent/primary care treatable conditions
      by teaching them how to proactively manage their health and adhere to therapeutic
      regimens. Programmatic reasons for these improvements may include psychosocial
      bonding with participants who received in-home care, health coaching, and the MIH
      team's 24/7 availability that provided immediate healthcare access.

PMID- 28495032
TI  - Meat science from 1976: A history of the journal.
AB  - The journal Meat Science was first published in 1976/77 and it initially
      comprised 4 issues per year. The first issue contained 4 papers and the first
      volume (4 issues) contained 27 articles, a mixture of papers and research notes.
      Its growth/popularity increased, and it has continued to thrive and in 2016 of
      the 1010 papers processed 292 were accepted. Over 90% of the papers published in
      the first volume were concerned with muscle biochemistry/meat properties. During
      the last years of the 20th century, meat products and their properties became a
      far larger proportion of the submissions as did those concerned with nutrition
      and safety. More recently there has been a resurgence of papers concerned with
      meat quality. Over the last 40years, the journal has reported on the major
      developments in meat science research and this paper will discuss both the
      history of the journal, and aspects of meat research as reflected in its
      publications. Possible future research trends are also discussed.

PMID- 28495033
TI  - Clinical applications of 3-dimensional printing in radiation therapy.
AB  - Three-dimensional (3D) printing is suitable for the fabrication of complex
      radiotherapy bolus. Although investigated from dosimetric and feasibility
      standpoints, there are few reports to date of its use for actual patient
      treatment. This study illustrates the versatile applications of 3D printing in
      clinical radiation oncology through a selection of patient cases, namely, to
      create bolus for photon and modulated electron radiotherapy (MERT), as well as
      applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were
      3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum
      and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a
      mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To
      treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was
      made. The structures' fit to the anatomy and the radiotherapy treatment plans
      were assessed. Based on the treatment planning computed tomography (CT), the size
      of the largest air gap at the interface of the 3D-printed structure was 3 mm for
      the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis
      fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment
      plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of
      planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of
      PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For
      the latter, compared with a plan with a uniform thickness bolus, the one
      featuring the MERT bolus achieved relative sparing of all the organs at risk
      (OARs) distal to the target volume, while maintaining similar target volume
      coverage. The surface brachytherapy plan for the SCC of the nose had adequate
      coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively
      high dose to the left eye, owing to its proximity to the tumor. 3D printing can
      be implemented effectively in the clinical setting to create highly conformal
      bolus for photon and MERT, as well as applicators for surface brachytherapy.

PMID- 28495034
TI  - [Presence of Acanthamoeba spp. in watering trough in La Pampa province,
      Argentina].
AB  - Free-living Amoebae of Acanthamoeba genus include non-pathogenic and pathogenic
      strains that are currently classified in 18 different genotypes, T1-T18. In this
      study, a survey was carried out to evaluate the presence of Acanthamoeba strains
      inwatering trough sample in La Pampa province, Argentina. Sample were inoculated
      onto non-nutrient agar plates and were checked for the presence of Acanthamoeba.
      Polymerase chain reaction was performed with genus-specific primers JDP1/JDP2,
      followed by direct sequencing of the polymerase chain reaction product for
      molecular identification. Sequencing results revealed the presence of T4, T5 and
      T15 genotypes within the studied samples. Sequencing revealed presence of T4, T5
      and T15 in the samples studied genotypes, the most frequent T4. Our study reveals
      importance of the presence of Acanthamoeba in the livestock environment and the
      need for further studies to associate the presence of these organisms and the
      role in veterinary pathology. To the best of our knowledge, this is the first
      report demonstrating the presence Acanthamoeba in La Pampa province and the first
      study at the genotype level in Argentina.

PMID- 28495035
TI  - Selection of Bacillus thuringiensis strains toxic to cotton boll weevil
      (Anthonomus grandis, Coleoptera: Curculionidae) larvae.
AB  - Preliminary bioassays with whole cultures (WC) of 124 Bacillus thuringiensis
      strains were performed with neonate larvae of Anthonomus grandis, a major cotton
      pest in Argentina and other regions of the Americas. Three exotic and four native
      strains were selected for causing more than 50% mortality. All of them were beta
      exotoxin producers. The native strains shared similar morphology of parasporal
      crystals, similar protein pattern and identical insecticidal gene profiles. These
      features resembled Lepidoptera-toxic strains. Furthermore, these strains showed a
      Rep-PCR pattern identical to lepidoptericidal strain HD-1, suggesting that these
      strains may belong to serovar kurstaki. However, some differences were observed
      in the plasmid profiles and in the production of beta-exotoxin. To determine the
      culture fractions where the insecticidal metabolites were present, bioassays
      including resuspended spore-crystal pellets, filtered supernatants (FS) were
      compared with those of WC. Both fractions tested showed some level of
      insecticidal activity. The results may suggest that the main toxic factors can be
      found in FS and could be directly correlated with the presence of beta-exotoxin.
      Based on the bioassays with FS and autoclaved FS, the participation of
      thermolabile virulence factors such as Cry1I in toxicity is neither discarded. In
      the selected strains, beta-exotoxin would be the major associated virulence
      factor; therefore, their use in biological control of A. grandis should be
      restricted. Nevertheless, these strains could be the source of genes (e.g.,
      cry1Ia) to produce transgenic cotton plants resistant to this pest.

PMID- 28495036
TI  - Fungal endophytes isolated from Protium heptaphyllum and Trattinnickia rhoifolia
      as antagonists of Fusarium oxysporum.
AB  - Control of fungal pathogens is mainly addressed by the use of chemically
      synthesized fungicides which result in environmental pollution, developing
      resistance after prolonged use. In this context, endophytes have been recognized
      as potential biocontrollers, and also as a promising source of antifungal
      metabolites. Therefore, as part of our research on phytopathogen controllers, 355
      fungal endophytes were isolated from Protium heptaphyllum and Trattinnickia
      rhoifolia (Burseraceae), both ethnobotanically important tree species that
      produce secondary metabolites of agronomic and industrial interest. Endophytes
      were tested by in vitro dual culture against Fusarium oxysporum, a phytopathogen
      of agronomic importance. Five endophytes exerted at least 40% inhibition on F.
      oxysporum growth. Ethyl acetate (EtOAc) extracts were obtained from the most
      active antagonistic fungi, after growing them in three different liquid media.
      The extracts were tested against a conidial suspension of F. oxysporum by direct
      bioautography. Two extracts derived from fungi identified as Chaetomium globosum,
      F211_UMNG and Meyerozima sp. F281_UMNG showed inhibition of pathogen growth.
      Isolate C. globosum, F211_UMNG was selected for a chemical analysis by RP-HPLC
      DAD-ESI-MS and antifungal molecules such as cladosporin, chaetoatrosin A and
      chaetoviridin A were annotated and identified based on their MS data.

PMID- 28495037
TI  - Efforts to Increase Global Food Security: Implications for International
      Nutrition Education.

PMID- 28495038
TI  - More Than Reading, Writing, and Arithmetic.

PMID- 28495039
TI  - Emotional Symptoms and Dietary Patterns in Early Adolescence: A School-Based
      Follow-up Study.
AB  - OBJECTIVE: To examine the relationship between early emotional symptoms and
      dietary patterns over 3 years in a school-based sample. DESIGN: Three-year
      longitudinal prospective study. SETTING: Thirteen schools in Reus, Spain.
      PARTICIPANTS: From a sample of 562 preadolescents with and without emotional
      symptoms, 165 were observed and were classified as either showing (n = 100) or
      not showing emotional symptoms (n = 65). MAIN OUTCOME MEASURE: Emotional symptoms
      were assessed at baseline and after 1 and 3 years. In the third year, data were
      collected on food consumption, adherence to the Mediterranean diet (MD), and
      physical activity. ANALYSIS: Dietary patterns were created by principal component
      analysis. Multivariate logistic regression was conducted with P < .05 considered
      significant. RESULTS: Girls with emotional symptoms scored significantly lower in
      assessments for MD (score of 5.41 +/- 2.19) and physical activity (score of 4.97
      +/- 2.05) than did girls who had no emotional symptoms (scores: MD, 6.19 +/-
      1.67; physical activity: 5.86 +/- 1.94). Approximately 39.68% of girls with
      emotional symptoms showed high adherence to a sweet and fatty food pattern. After
      adjusted logistic regression, girls with emotional symptoms were 4 times as
      likely to have high adherence to a sweet and fatty food pattern (odds ratio,
      4.79; 95% confidence interval, 1.55-15.10). No differences were observed among
      boys. CONCLUSIONS AND IMPLICATIONS: Girls with emotional symptoms during early
      adolescence have high adherence to a pattern rich in sweet and fat foods and low
      adherence to MD, and engage in low levels of physical activity. These findings
      highlight the importance of managing emotional distress to prevent it from having
      a negative effect on eating behavior.

PMID- 28495040
TI  - Overweight and Obesity, Weight Perception, and Weight Management Practices Among
      Supplemental Nutrition Assistance Program-Education (SNAP-Ed) Participants in
      Georgia: A Needs Assessment.
AB  - OBJECTIVE: Examine associations among weight status, weight perception, and
      weight management practices of Supplemental Nutrition Assistance Program
      Education (SNAP-Ed) participants in Georgia. METHODS: Self-reported weight,
      height, and weight-related practices were assessed and analyzed in 270 SNAP-Ed
      participants. RESULTS: Almost three quarters of the sample self-reported
      overweight or obesity. Among overweight and obese subjects, 39% and 69%,
      respectively, accurately perceived themselves as overweight. More than half of
      the sample desired weight loss and 44% had attempted weight loss in the past
      year. Overweight/obese subjects who accurately perceived their weight were more
      likely to desire and to have attempted weight loss than those who under-perceived
      their weight. Approximately 58% of all subjects who had attempted to lose weight
      reported use of both methods suggested for weight loss: exercise and dietary
      changes. CONCLUSIONS AND IMPLICATIONS: The high prevalence of self-reported
      overweight/obesity combined with a desire to lose weight among the study sample
      demonstrated the necessity to develop SNAP-Ed curricula emphasizing weight
      management.

PMID- 28495041
TI  - Staff Workshop Improves Child Care Center Menus in South Central Texas: A Best
      Food for Families, Infants, and Toddlers (Best Food FITS) Intervention.
AB  - OBJECTIVE: To assess the efficacy of an educational workshop for child care
      center staff to improve menus. METHODS: Staff from 18 centers attended a
      nutrition educational workshop that included an activity that compared center
      menus to MyPlate standards. Four weeks of menus collected before and after the
      workshop were imported into SuperTracker; the Food Details report produced menu
      data clustered by day and center. Changes in pre-post menus were assessed using
      Healthy Eating Index scores and the SAS software macro, MIXCORR. RESULTS: After
      the workshop, there was a lower probability that fruit juice (P = .03) and
      starchy vegetables (P = .004) and a higher probability that non-starchy
      vegetables (P < .001) and whole grains (P = .004) were on menus; amounts of
      refined grains (P = .004), savory snacks (P < .001), and cheese (P = .004) were
      significantly lower. Total Healthy Eating Index scores improved after the
      workshop (P = .009). CONCLUSIONS AND IMPLICATIONS: Comparing 4 weeks of menus
      revealed menu changes. Workshop interventions show promise for improving
      children's health.

PMID- 28495042
TI  - Confirming the Reliability and Validity of Others' Evaluation Tools Before
      Adopting for Your Programs.
AB  - OBJECTIVE: To confirm the reliability and validity of a previously validated
      evaluation instrument in a new context. METHODS: In a cross-sectional study, the
      processes and results of testing Cooking Matters' (CM) use of the Expanded Food
      and Nutrition Education Program's Behavior Checklist as a retrospective
      pretest/posttest were described. The researchers determined reliability, face and
      content validity, and response-shift bias with 95 CM participants. RESULTS: Most
      items had acceptable face validity and moderate reliability; other items lacked
      reliability, or face or content validity (were unrelated to the CM curriculum).
      CONCLUSIONS AND IMPLICATIONS: Proper match between evaluation tools and curricula
      is needed for appropriate program assessment without which outcome data can be
      misleading or potentially invalid. Confirmation of validity is essential when
      adopting others' evaluation tools in new contexts, particularly for programs with
      widespread use such as federally funded programs and national nonprofit
      organizations.

PMID- 28495043
TI  - Setting Research Priorities for Kidney Cancer.
AB  - Defining disease-specific research priorities in cancer can facilitate better
      allocation of limited resources. Involving patients and caregivers as well as
      expert clinicians in this process is of value. We undertook this approach for
      kidney cancer as an example. The Kidney Cancer Research Network of Canada
      sponsored a collaborative consensus-based priority-setting partnership that
      identified ten research priorities in the management of kidney cancer. These are
      discussed in the context of current initiatives and gaps in knowledge.

PMID- 28495045
TI  - Deterioration in gait and functional ambulation in children and adolescents with
      Charcot-Marie-Tooth disease over 12 months.
AB  - Children and adolescents with Charcot-Marie-Tooth disease (CMT) report problems
      with gait. Little is known about gait changes over time in children with this
      degenerative disease. This prospective longitudinal study investigated change in
      spatio-temporal gait parameters and functional ambulation. Two assessments were
      conducted 12 months apart. Assessments included: barefoot gait on an electronic
      walkway; functional ambulation with a six minute walk test and the Functional
      Mobility Scale; and disease severity with the CMT Pediatric Scale. Gait and
      strength data were normalised to body anthropometrics. Twenty-seven children
      (mean age 12.2, SD 3.7 years) with various CMT subtypes (CMT1A 52%) were
      evaluated. Over 12 months, normalised variables of gait speed, stride length and
      six minute walk distance significantly decreased. The CMT Pediatric Scale
      increased 0.7 points, indicating marginal but not significant worsening of
      disease; notably calf strength decreased significantly over 12 months. Baseline
      maximum ankle dorsiflexion angle, gastrocnemius and hamstrings length, and calf
      strength correlated with decline in gait speed, with maximum ankle dorsiflexion
      angle as the strongest predictor. Deterioration over one year in normalised
      variables of gait speed, stride length and distance walked in six minutes are
      indicators of functional decline and disease progression in children and
      adolescents with CMT.

PMID- 28495044
TI  - Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe
      disease: A longitudinal follow-up.
AB  - This study examines the long-term cognitive and academic outcomes of 11
      individuals with infantile onset Pompe disease (IOPD) (median age=11years,
      1month, range=5years, 6months through 17years of age) treated with enzyme
      replacement therapy from an early age. All participants (7 males, 4 females) were
      administered individual intelligence tests (Wechsler or Leiter scales or both), a
      measure of their academic skill levels (Woodcock-Johnson Tests of Achievement),
      and a screening measure of visual-motor integration ability (Beery-Buktenica).
      Consistent with our earlier findings, median IQ scores for the entire group on
      the Wechsler (median=84) and Leiter (median=92) scales continue to fall at the
      lower end of the average range compared to same-aged peers. The median scores for
      the group on a measure of visual-motor integration (median=76), visual perception
      (median=74) and motor coordination (median=60) were below average. Two distinct
      subgroups emerged based on participants' average or below average performance on
      the majority of academic subtests. Those participants with below average academic
      skills (n=6) demonstrated average nonverbal cognitive abilities on the Leiter,
      but had weaknesses in speech and language skills and greater medical involvement.
      Their profiles were more consistent with a learning disability diagnosis than an
      intellectual disability. Two of these participants showed a significant decline
      (15 and 23 points, respectively) on repeated Wechsler scales, but one continued
      to earn average scores on the Leiter scales where the verbal and motor demands
      are minimal. Participants with average academic skills (n=5) demonstrated average
      cognitive abilities (verbal and nonverbal) on the Wechsler scales and less
      medical involvement. Their speech and language skills appeared to be more intact.
      However, both groups earned below average median scores on the Beery-Buktenica
      motor coordination task. This study highlights the importance of using
      appropriate tests to capture both verbal and nonverbal abilities, considering
      each individual's motor skills, speech and language abilities, hearing status and
      native language. This will allow for a more accurate assessment of whether there
      is a learning disability or an intellectual disability. Long-term outcomes may be
      related to the stability of an individual's expressive and/or receptive language
      abilities over time. Changes in the speech and language domain may account for
      the decline in IQ observed in some IOPD long-term survivors, reflecting a
      learning disability rather than a decline in overall cognition or an intellectual
      disability. These observations, in conjunction with neuroimaging, will further
      our understanding of the neurocognitive profile of long-term IOPD survivors.

PMID- 28495046
TI  - Transient neonatal myasthenia gravis due to a mother with ocular onset of anti
      muscle specific kinase myasthenia gravis.
AB  - We describe a 27-year-old pregnant female with new onset of conjugate gaze
      deficit during the third trimester of pregnancy. Repetitive nerve stimulation
      tests, neostigmine tests, and acetylcholine receptor antibody assays were all
      negative. The patient delivered a normal healthy baby at a local clinic via
      cesarean section. The baby became hypotonic and had respiratory failure several
      minutes after birth. The result of acetylcholine receptor antibody was negative
      in the neonate. The neonate became healthy spontaneously and was extubated after
      21 days of ventilation care. Two months after delivery, the mother developed
      ptosis and generalized symptoms and subsequent workup revealed she was muscle
      specific kinase (MuSK) antibody positive. The neonate was presumed to have an
      anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody
      testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is
      necessary in pregnant women who are presumed ocular myasthenia gravis to warn
      occurrence of transient neonatal myasthenia gravis.

PMID- 28495047
TI  - Similar clinical, pathological, and genetic features in Chinese patients with
      autosomal recessive and dominant Charcot-Marie-Tooth disease type 2K.
AB  - Mutations in the ganglioside-induced differentiation-associated protein 1 gene
      (GDAP1) cause rare subtypes of Charcot-Marie-Tooth disease (CMT2K and CMT4A).
      CMT2K is an axonal neuropathy while CMT4A is a demyelinating type. In a series of
      169 Chinese CMT patients (79 CMT1, 52 CMT2 and 38 unclassified), four unrelated
      patients (2.37%) were identified with GDAP1 mutations, including two with
      autosomal recessive CMT2K (AR-CMT2K) and two dominant CMT2K (AD-CMT2K). All
      patients had disease onset before 5 years of age, and presented with muscle
      weakness, atrophy, and mild sensory disturbance in distal limbs. Motor nerve
      conduction velocities of the median nerve were within normal ranges, and compound
      muscle action potential ranged from 1.5 to 3.8 mV. Sural nerve biopsy revealed
      loss of large myelinated fibers with regeneration clusters and a few onion bulbs.
      Electron microscopy showed mitochondrial aggregation in both axons and Schwann
      cells, and neurofilament accumulation in giant unmyelinated fibers. The p.H256R
      mutation was found in all patients with GDAP1 compound heterozygous mutations,
      suggesting that it might be a common mutation in Chinese patients. This study
      observed no difference in the disease onset, phenotype severity,
      electrophysiological findings, or pathological changes between AR-CMT2K and AD
      CMT2K patients.

PMID- 28495049
TI  - Selective or predominant triceps muscle weakness in African-American patients
      with myasthenia gravis.
AB  - Myasthenia gravis (MG) can lead to weakness in different patterns of muscle
      groups. Limb muscle weakness is most typically seen in a limb girdle pattern,
      although variants exist. In the current study, we aimed to describe a unique MG
      phenotype consisting of selective or predominant triceps muscle weakness. We
      performed a retrospective review of MG patients who developed focal or
      predominant triceps muscle weakness between 2006 and 2016. The clinical,
      electrophysiological and serological characteristics of these patients were
      examined. 8 MG patients were identified, including 7 males, all of whom were
      African-American. Two patients underwent muscle biopsy, and one patient underwent
      cervical spine decompression surgery. All showed significant improvement
      following immunosuppressive treatment, although one patient experienced a relapse
      of muscle weakness. This case series highlights a relatively uncommon MG clinical
      phenotype of selective triceps muscle weakness, mainly in African-American males,
      in line with previous literature. Familiarity with this phenotype is important in
      order to facilitate diagnosis and appropriate treatment for this group, and avoid
      unnecessary investigations or treatments.

PMID- 28495048
TI  - HLA and age of onset in myasthenia gravis.
AB  - The aetiology of MG is unknown, but both genetic and environmental factors are
      important. Over the years association of MG with Human Leucocyte Antigens (HLA)
      has been described in different populations. We investigated a possible
      association between HLA-DRB1 alleles and age of onset in MG. One hundred and
      fourteen MG patients (82 females) and 282 control individuals (CP) were studied.
      Patients were classified according to the age of onset (early-onset <50, n = 74
      and late-onset >= 50, n = 20). Patients with thymoma (n = 20) were analyzed
      separately. HLA-DRB1 and HLA-B*08 genotyping was performed using PCR-SSP
      methodology. HLA-DRB1*03 allele was overrepresented in the global MG. When the
      early-onset subgroup was considered, this association became even stronger.
      Regarding the late-onset subgroup, the frequency of HLA-DRB1*01 allele was higher
      than in the CP. For the thymoma subgroup, the HLA-DRB1*10 allele frequency was
      significantly higher when compared to the CP. These results have shown a strong
      association of HLA-DRB1*03 with MG, especially for EOMG also in our population.
      HLA-DRB1*01 was associated to LOMG suggesting that is a susceptibility factor for
      this subgroup of the disease. This study confirms a different genetic background
      of MG subgroups regarding age of onset.

PMID- 28495050
TI  - Deep intronic variants introduce DMD pseudoexon in patient with muscular
      dystrophy.
AB  - Dystrophinopathies are X-linked muscle diseases caused by mutations in the large
      DMD gene. The most common mutations are detected by standard diagnostic
      techniques. However, some patients remain without detectable mutation, most
      likely due to changes in the non-coding sequence. We report on a boy with
      complete absence of dystrophin in muscle biopsy but no causative mutation
      according to standard diagnostics. To search for deep intronic variations (DIV)
      in the DMD gene we isolated mRNA from muscle tissue and amplified overlapping
      cDNA fragments using RT-PCR. One cDNA product revealed an augmented fragment size
      showing an insertion of 77 bp between the exons 7 and 8 by sequencing. We
      sequenced the flanking sequences of gDNA and found two hemizygous single
      nucleotide variants (c.650-39575 A>C and c.650-39498 A>G) surrounding the
      inserted fragment. Both variants create cryptic splice sites which initiate the
      formation of a pseudoexon that produces a frameshift in the DMD gene.

PMID- 28495051
TI  - Bone histological correlates of soaring and high-frequency flapping flight in the
      furculae of birds.
AB  - The furcula is a specialized bone in birds involved in flight function. Its
      morphology has been shown to reflect different flight styles from soaring/gliding
      birds, subaqueous flight to high-frequency flapping flyers. The strain
      experienced by furculae can vary depending on flight type. Bone remodeling is a
      response to damage incurred from different strain magnitudes and types. In this
      study, we tested whether a bone microstructural feature, namely Haversian bone
      density, differs in birds with different flight styles, and reassessed previous
      work using phylogenetic comparative methods that assume an evolutionary model
      with additional taxa. We show that soaring birds have higher Haversian bone
      densities than birds with a flapping style of flight. This result is probably
      linked to the fact that the furculae of soaring birds provide less protraction
      force and more depression force than furculae of birds showing other kinds of
      flight. The whole bone area is another explanatory factor, which confirms the
      fact that size is an important consideration in Haversian bone development. All
      birds, however, display Haversian bone development in their furculae, and other
      factors like age could be affecting the response of Haversian bone development.

PMID- 28495052
TI  - Geographic variation in factors that influence timing of moult and breeding in
      waterfowl.
AB  - Waterfowl flight-feather moult is expected to occur when energy is not needed for
      breeding and when a suitable safe habitat is available. Flight-feather regrowth
      is an energetically costly stage in the annual cycle of waterfowls. In this
      study, we tested the hypothesis that moult will coincide with the time of year
      when food and aquatic habitats are most abundant. We investigated how the timing
      of rainfall relates to the timing of breeding and flight-feather moult in five
      common southern African waterfowl at two sites in South Africa with opposite
      rainfall regimes (one summer, one winter). We then incorporated published data to
      compare and contrast the relative timing of breeding and moult in southern
      hemisphere (southern African and Australian) waterfowl with northern hemisphere
      (European and North American) species. Our results showed that southern African
      waterfowl breed in the wet season and moult during the dry season. Tadorna cana
      was an exception, breeding in the dry season and moulting during the wet season
      in the summer-rainfall area. There was also a long lag period between peak
      breeding and peak moult in southern hemisphere waterfowl species, the longest lag
      being that of birds in the summer-rainfall area. By comparison, northern
      hemisphere waterfowl species breed and moult during the warm season, with a
      shorter lag period between peak breeding and peak moult compared to southern
      hemisphere species. We concluded that waterfowl in southern Africa (with the
      exception of T. cana), southeast Australia, Europe and North America time their
      breeding period to coincide with peaks in the availability of both food and
      breeding sites. Northern hemisphere species moult where chances of predation are
      low, when temperatures are warm, and before food and aquatic habitats approach
      their winter minima. By contrast, southern hemisphere waterfowl delay the onset
      of moult until the dry season, opting to moult when both food and aquatic
      moulting habitats are scarce.

PMID- 28495053
TI  - Evaluation of Preoperative Aspartate Transaminase/Alanine Transaminase Ratio as
      an Independent Predictive Biomarker in Patients With Metastatic Renal Cell
      Carcinoma Undergoing Cytoreductive Nephrectomy: A Propensity Score Matching
      Study.
AB  - BACKGROUND: The usefulness of the aspartate transaminase (AST)/alanine
      transaminase (ALT) ratio (De Ritis ratio) as a predictive biomarker for patients
      with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy
      (CN) remains unclear. PATIENTS AND METHODS: The data from 118 patients were
      retrospectively evaluated. The endpoints were cancer-specific survival (CSS) and
      overall survival (OS) after CN. We compared these according to the AST/ALT ratio
      before and after 1:1 propensity score matching. The independent predictors for
      CSS and OS were also analyzed. RESULTS: The area under the receiver operating
      characteristic curve was 0.603. The maximum Youden index indicated that the
      cutoff value for the AST/ALT ratio was 1.24. Before matching, a high AST/ALT
      ratio was significantly associated with inferior CSS and OS (P < .05 for all).
      After matching, 34 patients each were allocated to the high and low AST/ALT ratio
      groups. In the matched cohort, CSS and OS tended to be lower in the high AST/ALT
      ratio group, although the results were not statistically significant (median CSS,
      18.4 months vs. not reached, P = .121; OS, 18.4 months vs. not reached, P =
      .0957). Furthermore, multivariate analyses revealed that the AST/ALT ratio was an
      independent predictor for CSS and OS (CSS hazard ratio, 2.17, P = .0472; OS
      hazard ratio, 2.30, P = .0258). CONCLUSION: The preoperative AST/ALT ratio can be
      an effective predictive biomarker for CSS and OS in patients with mRCC.

PMID- 28495054
TI  - Phasic availability of terminal electron acceptor on oxygen reduction reaction in
      microbial fuel cell.
AB  - Oxygen-reduction reactions (ORR) plays a pivotal role in determining microbial
      fuel cells (MFC) performance. In this study, an attempt to determine the
      influence of the phasic availability of terminal electron acceptor (TEA) on ORR
      was made. Two MFCs operated with dissolved oxygen (MFC-DC) and air (MFC-SC) as
      TEA were constructed and analyzed in continuous mode under open and closed
      circuit conditions. The bio-electrochemical analysis showed a marked influence of
      dissolved oxygen resulting in a maximum power density with MFC-DC (769mW/m2)
      compared to MFC-SC (684mW/m2). The availability of O2 in dissolved phase has
      lowered the activation losses during the MFC operation as a result of effective
      ORR. The cyclic voltammetry analysis revealed the TEA dependent biocatalyst
      activity of NADH and cytochrome complex which enabled electron transfer kinetics
      and improved substrate utilization. Finally, the study evidenced the critical
      role of TEA phasic availability to regulate the bio-electrogenic and substrate
      degradation potential in MFC.

PMID- 28495055
TI  - Production and characterization of chars from cherry pulp via pyrolysis.
AB  - Pyrolysis is an eco-friendly process to achieve valuable products like bio-oil,
      char and gases. In the last decades, biochar production from pyrolysis of a wide
      variety of industrial and agricultural wastes become popular, which can be
      utilized as adsorbent instead of the expensive activated carbons. In this study,
      cherry pulp was pyrolyzed in a fixed bed tubular reactor at five different
      temperatures (400, 500,550, 600 and 700  degrees C) and three different heating
      rates (10, 100 and 200  degrees C/min) to obtain biochar. Proximate, ultimate,
      nitrogen adsorption/desorption isotherms, scanning electron microscopy,
      thermogravimetric analysis, x-ray fluorescence, x-ray diffraction, and Fourier
      transform infrared spectroscopy were performed on cherry pulp and its chars to
      examine the chemical alterations after the pyrolysis process. Biochar yields were
      decreased with increasing pyrolysis temperature and heating rate, based on
      experimental results. Porous biochars are carbon rich and includes high potassium
      content. The aromaticity of biochars increased and O/C mass ratio reduced with an
      increase in the pyrolysis temperature as a result of the development of compact
      aromatic structure in char. Pyrolysis provides a promising conversion procedure
      for the production of high energy density char which has promising applications
      in existing coal-fired boilers without any upgrading.

PMID- 28495056
TI  - A novel minimally invasive near-infrared thoracoscopic localization technique of
      small pulmonary nodules: A phase I feasibility trial.
AB  - OBJECTIVES: Localization and resection of nonvisible, nonpalpable pulmonary
      nodules during video-assisted thoracoscopic surgery are challenging. Our study
      was to determine the feasibility and safety of indocyanine green fluorescence
      localization and resection of small nodules using a near-infrared fluorescence
      thoracoscope. METHODS: Twenty patients with undiagnosed peripheral nodules
      smaller than 3 cm scheduled for computed tomography-guided microcoil placement
      followed by video-assisted thoracoscopic surgery wedge resection were enrolled.
      After microcoil deployment, 100 to 150 MUL of diluted indocyanine green was
      injected percutaneously near the nodule. The nodule initially was localized
      solely by using a near-infrared thoracoscope to visualize indocyanine green
      fluorescence. Thoracoscopic instruments were used to determine the staple line.
      Wedge resection was performed after confirmation of the location of the microcoil
      using fluoroscopy. RESULTS: Twenty patients underwent near-infrared, image
      guided, video-assisted thoracoscopic surgery resection. The median computed
      tomography tumor size was 1.2 cm. The median depth from the pleural surface was
      1.4 cm (range, 0.2-4.8 cm). The median computed tomography-guided intervention
      time was 35 minutes, and video-assisted thoracoscopic surgery procedural time was
      54 minutes. Indocyanine green fluorescence was clearly identified in 18 of 20
      patients (90%). The surgical margins were all negative on final pathology without
      the need for additional resection. The final diagnoses included 18 primary lung
      cancers, 1 metastatic lung cancer, and 1 benign lung tumor. CONCLUSIONS: Computed
      tomography-guided percutaneous indocyanine green injection and intraoperative
      near-infrared localization of small nodules are safe and feasible. These offer
      surgeons the ease of localization through direct indocyanine green fluorescence
      imaging without the use of fluoroscopy and may be a complementary technique to
      preoperative microcoil placement for nonvisible, nonpalpable intrapulmonary
      nodules.

PMID- 28495057
TI  - Cardiac surgery training in Canada: Current state and future perspectives.

PMID- 28495058
TI  - miRNA profiling of primary lung and head and neck squamous cell carcinomas:
      Addressing a diagnostic dilemma.
AB  - OBJECTIVE: To determine whether microRNA (miRNA) profiling of primary lung and
      head and neck squamous cell carcinomas could be useful to identify a specific
      miRNA signature that can be used to further discriminate between primary lung
      squamous carcinomas and metastatic lesions in patients with a history of head and
      neck squamous cell cancer. METHODS: Specimens of resected primary head and neck
      and lung squamous cell carcinomas were obtained from formalin-fixed, paraffin
      embedded blocks. Paraffin blocks were sectioned and deparaffinized, and total RNA
      was isolated and profiled. Quantitative polymerase chain reaction was performed
      to verify array results. RESULTS: Twelve head and neck and 16 lung squamous cell
      carcinoma samples met quality control metrics and were included for analysis.
      Forty-eight miRNAs were differentially expressed (P < .05) between the 2 groups.
      Of these, 30 were also significantly associated (q < .25) with tumor type in 2
      independent sets of primary head and neck and lung squamous carcinomas profiled
      by The Cancer Genome Atlas consortium, including miR-34a and miR-10a. The ratio
      of miR-10a and miR-10b was especially predictive of primary cancer site in all 3
      data sets, with area under the (receiver operating characteristics) curve values
      ranging from 0.922 to 0.982. Quantitative polymerase chain reaction confirmed the
      association of miR-34a expression and the miR-10:miR-10b ratio with tumor type.
      CONCLUSIONS: MicroRNA expression may be useful for discriminating between head
      and neck and lung squamous cell carcinomas, including miR-34a and the miR-10a:miR
      10b ratio. This differentiation has clinical importance because it could help
      determine the appropriate therapeutic approach.

PMID- 28495059
TI  - Bicuspid aortic valve aortopathy is not cancer.

PMID- 28495060
TI  - Hot nodules and histologic features: The emerging story of stage IA lung
      adenocarcinoma.

PMID- 28495061
TI  - High-risk cardiac surgery as an alternative to transplant or mechanical support
      in patients with end-stage heart failure.
AB  - OBJECTIVE: Although the results of cardiac surgery in patients with poor left
      ventricular function have been widely published, the outcomes in patients with
      end-stage heart failure who meet criteria for advanced therapies are not well
      investigated. As access to transplantation and ventricular assist device therapy
      remains limited, we explored the possibility of conventional surgery as an
      alternative option for highly selected patients with end-stage heart failure.
      METHODS: We identified patients with left ventricular ejection fraction <20% and
      VO2 max <14 mL/min/m2, who were initially referred for advanced therapies but
      were instead offered a conventional procedure from 2002 to 2012. We examined the
      short- and midterm outcomes and compared survival with that after our advanced
      therapies in the same era. RESULTS: A total of 133 patients were identified; 68
      were deemed to be transplant-eligible, whereas 65 were transplant-ineligible.
      Seventy-nine percent were in New York Heart Association class III/IV. In-hospital
      mortality was 12%. Actuarial survival at 5 and 10 years was 72% +/- 4% and 39% +/
      8%, respectively. Nonischemic etiology was identified as a predictor of late
      mortality. In the propensity-adjusted model, our transplant-eligible patients had
      comparable long-term survival to our transplantation patients (HR 1.48 [95%
      confidence interval, 0.66-3.2], P = .34), whereas the survival in our transplant
      ineligible subset was comparable to the survival after our left ventricular
      assist device therapy (HR 0.49 [95% confidence interval, 0.16-1.50], P = .21).
      CONCLUSIONS: Despite high perioperative risk, the midterm survival after
      conventional surgery in patients eligible for advanced therapies seems to be
      acceptable and may be an alternative option for highly selected patients with end
      stage heart failure.

PMID- 28495062
TI  - Discussion.

PMID- 28495064
TI  - Discussion.

PMID- 28495063
TI  - Topical amiodarone during cardiac surgery: Does epicardial application of
      amiodarone prevent postoperative atrial fibrillation?
AB  - OBJECTIVES: Atrial fibrillation (AF) is a common complication after cardiac
      surgery. Topical amiodarone on the epicardium may help prevent postoperative AF
      while avoiding the side effects of its systemic administration. The purpose of
      this study was to evaluate the all-comer strategy of epicardial amiodarone
      application for the prevention of postoperative AF. METHODS: A retrospective
      observational study was performed that evaluated the incidence of new-onset AF in
      a consecutive series of cardiac surgery patients who were treated with either no
      amiodarone (historical control, n = 100), epicardial application of amiodarone
      mixed in a topical hydrogel (n = 50), or epicardial application of an amiodarone
      soaked sealant patch (n = 50). Perioperative data were compared between the 3
      groups, with all patients receiving continuous postoperative telemetry to monitor
      for new-onset AF. RESULTS: The cohort consisted of 200 cardiac surgery patients
      (coronary bypass 82%, valve surgery 24%) who had no history of AF (mean age 71.0
      years, 28% female). Among the 3 groups, the incidence of postoperative AF did not
      significantly differ, with 29 of 100 (29%) patients in the historical control
      group having new AF, compared with 18 of 50 (36%) in the amiodarone-hydrogel
      group, and 18 of 50 (36%) in the amiodarone-patch group (P = .56). The results
      did not differ when the analysis was restricted to coronary bypass patients only
      (n = 142, 27% vs 38% vs 32%, no-amiodarone vs amiodarone-hydrogel vs amiodarone
      patch, respectively, P = .56). In multivariate logistic regression analysis, only
      older age (P = .001) was significantly associated with new-onset AF, but the use
      of topical amiodarone was not. CONCLUSIONS: Routine epicardial application of
      topical amiodarone was not associated with a reduction in the incidence of new
      onset postoperative AF in this observational study of older patients, leading us
      to question its role in contemporary cardiac surgical practice.

PMID- 28495065
TI  - The miniaturized pediatric continuous-flow device: Preclinical assessment in the
      chronic sheep model.
AB  - BACKGROUND: The Infant Jarvik 2015 is an implantable axial-flow ventricular
      assist device (VAD) that has undergone the major evolutionary design
      modifications to improve hemocompatibility. This study was conducted in
      anticipation of data submission to the US Food and Drug Administration to obtain
      Investigational Device Exemption approval. METHODS: The VAD was implanted via a
      left thoracotomy in Barbado sheep (n = 10, 26 (19-34] kg). Anticoagulation was
      maintained with coumadin, with a target international normalized ratio of greater
      than the individual sheep's baseline values. The VAD was managed at the highest
      possible speed as clinically tolerable. Complete necropsy was performed at the
      end of the study. RESULTS: There were 2 early mortalities: tension pneumothorax
      (n = 1) and shower emboli of the fragmented myocardium (n = 1). The remaining 8
      sheep (2 with 30-day and 6 with 60-day protocols) completed the anticipated study
      duration in excellent condition, with the 6 completing 60-day sheep showing
      appropriate weight gain during support. There were no signs of clinically
      significant hemolysis, with the final plasma-free hemoglobin of 2 (1-17) mg/dL.
      Necropsy showed old renal infarction in 7 sheep. Although thromboembolism can be
      the potential etiology, given the mild anticoagulation regimen, other sources of
      emboli were identified in 2 sheep (graft coating material and fragmented
      myocardium). Flow study demonstrated favorable increase in flow (up to 3.0 L/min)
      in proportion to change in pump speed. CONCLUSIONS: This study has demonstrated
      that the Infant Jarvik 2015 VAD is capable of maintaining its functionality for
      an extended period of time with minimal hemolysis.

PMID- 28495066
TI  - Salvage pulmonary resection after stereotactic body radiotherapy: A feasible and
      safe option for local failure in selected patients.
AB  - OBJECTIVE: For inoperable patients with pulmonary malignancy, stereotactic body
      radiotherapy is a reasonable therapeutic option. Despite good early tumor
      control, local failure occurs in up to 10% of patients by 3 years. Because
      management of local recurrence after stereotactic body radiotherapy is unclear,
      we evaluated use of surgery as a salvage option. METHODS: A retrospective review
      was conducted of consecutive patients from a single institution who underwent
      salvage resection of primary and metastatic pulmonary malignancies previously
      treated with stereotactic body radiotherapy. In addition, a literature search was
      conducted to identify previous reports of pulmonary resection for local
      stereotactic body radiotherapy failures, to allow cumulative analyses with
      previously published cases. RESULTS: A total of 21 patients met inclusion
      criteria. The median time between stereotactic body radiotherapy and salvage
      surgery was 16.2 months (range, 6.4-71.5). Postoperative complications occurred
      in 7 patients (18.9%), in whom atrial arrhythmias and prolonged air leaks (>5
      days) were most frequent (n = 2 each, 5.4%). There was no local recurrence after
      salvage surgery. Distant failure occurred in 5 of 21 patients (23.8%) at a median
      of 36.2 months, and median disease-free survival was 19.2 months. The 30- and 90
      day mortality was 4.8% (1 patient). Cumulative analysis included 37 patients from
      4 institutions and comprised 26 (78.8%) primary non-small cell lung cancers and
      11 (29.7%) lung metastases. Median overall survival after salvage surgery was
      46.9 months, and 3-year survival was 71.8%. CONCLUSIONS: After local failure of
      stereotactic body radiotherapy, salvage resection remains a viable option for
      operable patients, with acceptable morbidity and survival. As use of stereotactic
      body radiotherapy continues to expand, further studies to evaluate the optimal
      management for local failure are needed.

PMID- 28495067
TI  - Discussion.

PMID- 28495068
TI  - Discussion.

PMID- 28495069
TI  - The importance of arch geometry after Norwood reconstruction.

PMID- 28495071
TI  - Perioperative and economic analysis of surgical treatments for benign prostatic
      hyperplasia: A study of the French committee on LUT.
AB  - PURPOSE: To evaluate perioperative cost related to surgical treatments of benign
      prostatic obstruction (BPO): photoselective vaporization of the prostate (pvp),
      holmium/thullium laser enucleation (HoLEP/ThuLEP), transurethral resection of the
      prostate (TURP) and open prostatectomy (OP). MATERIAL AND METHODS: We
      retrospectively collected data from 237 patients who consecutively underwent a
      surgical treatment for BPH between January 2012 and June 2013 at nine
      institutions in France. An economic simulation model was constructed to estimate
      the cost of hospitalization related to surgical procedure from the hospital
      perspective and a cost minimization analysis was performed. RESULTS: TURP, OP,
      HoLEP/ThuLEP and PVP were performed in 99 (42%), 23 (10%), 64 (27%) and 51 (21%)
      patients, respectively. For men with prostate size<80mL: mean operative time was
      shorter with mTURP and PVP than HoLEP/thuLEP (P<0.001); Mean postoperative length
      of stay were 1.9, 3 vs. 3.4 days, for HoLEP/Thulep, PVP and TURP respectively
      (P=0.006); Costs of first hospitalization were comparable between HoLEP/ThuLEP
      and TURP but higher with PVP (P<0.001). For men with prostate size>=80mL:
      Compared to PVP and HoLEP/ThuLEP, OP was associated with shorter operative time
      (P<0.001) but longer length of stay (2.4, 4.2 vs. 7.8 days, respectively,
      P<0.0001); Costs of first hospitalization were significantly higher with OP than
      HoLEP/ThuLEP or PVP (P<0.001). CONCLUSIONS: PVP and HoLEP/ThuLEP were associated
      with a shorter LOS than TURP and OP. This benefit suggests these procedures could
      be more cost effective than OP, but still not cheaper alternatives to TURP. LEVEL
      OF EVIDENCE: 5.

PMID- 28495072
TI  - Reprint of "Application of next generation sequencing in clinical microbiology
      and infection prevention".
AB  - Current molecular diagnostics of human pathogens provide limited information that
      is often not sufficient for outbreak and transmission investigation. Next
      generation sequencing (NGS) determines the DNA sequence of a complete bacterial
      genome in a single sequence run, and from these data, information on resistance
      and virulence, as well as information for typing is obtained, useful for outbreak
      investigation. The obtained genome data can be further used for the development
      of an outbreak-specific screening test. In this review, a general introduction to
      NGS is presented, including the library preparation and the major characteristics
      of the most common NGS platforms, such as the MiSeq (Illumina) and the Ion PGMTM
      (ThermoFisher). An overview of the software used for NGS data analyses used at
      the medical microbiology diagnostic laboratory in the University Medical Center
      Groningen in The Netherlands is given. Furthermore, applications of NGS in the
      clinical setting are described, such as outbreak management, molecular case
      finding, characterization and surveillance of pathogens, rapid identification of
      bacteria using the 16S-23S rRNA region, taxonomy, metagenomics approaches on
      clinical samples, and the determination of the transmission of zoonotic micro
      organisms from animals to humans. Finally, we share our vision on the use of NGS
      in personalised microbiology in the near future, pointing out specific
      requirements.

PMID- 28495070
TI  - Is social support associated with post-transplant medication adherence and
      outcomes? A systematic review and meta-analysis.
AB  - Although social support is used to determine transplant eligibility, the
      relationship between social support, medication adherence, and survival among
      transplant recipients remains unclear. We estimated the relationship between
      social support and post-transplant medication adherence and outcomes using 10
      electronic databases from inception to January 2016. Study quality was assessed
      and all review stages were conducted independently by 2 reviewers. Systematic
      review and meta-analysis were conducted. Thirty-two studies (9102 participants)
      met inclusion criteria: 21 assessed medication adherence (5197 participants), and
      13 assessed clinical outcomes (3905 participants). Among high quality studies,
      neither social support nor marital status was predictive of medication adherence
      or post-transplant outcomes. Social support was not associated with medication
      adherence. It was associated with superior post-transplant outcomes, but the
      relationship was not significant among high quality studies. Compared to
      unmarried recipients, married recipients were more likely to adhere to medication
      post-transplant, but this relationship was not significant among high quality
      studies. Marital status was not significantly associated with transplant success.
      Social support is weakly and inconsistently associated with post-transplant
      adherence and outcomes. Larger prospective studies using consistent and validated
      measures are needed to justify the use of inadequate social support as a
      contraindication to transplantation.

PMID- 28495074
TI  - The Rationale for GesEPOC in Our Environment.

PMID- 28495073
TI  - Expert Statement on the Single-Agent Use of Inhaled Bronchodilator in the
      Treatment of Stable Mild-Moderate Chronic Obstructive Pulmonary Disease.
AB  - OBJECTIVE: To describe the evidence- and experience-based expert consensus on the
      use of single-agent bronchodilators in patients with stable mild-moderate chronic
      obstructive pulmonary disease (COPD). METHODS: Using Delphi methodology, a panel
      of 7 respiratory medicine experts was established, who, in the first nominal
      group meeting defined the scope, users, and document sections. The panel drew up
      14 questions on the use of single-agent bronchodilators in patients with mild
      moderate stable COPD to be answered with a systematic review of the literature.
      The results of the review were discussed in a second nominal group meeting and 17
      statements were generated. Agreement/disagreement with the statements was tested
      among16 different experts including respiratory medicine experts and primary care
      physicians. Statements were scored from1 (total disagreement) to10 (total
      agreement). Agreement was considered if at least 70% voted >=7. The level of
      evidence and grade of recommendation of the systematic literature review was
      assessed using the Oxford Centre for Evidence-based Medicine levels. RESULTS: A
      total of 12 of the 17 statements were selected. Specific statements were
      generated on different profiles of patients with stable mild-moderate COPD in
      whom single-agent bronchodilators could be prescribed. CONCLUSIONS: These
      statements on the use of single-agent bronchodilators might improve the outcomes
      and prognosis of patients with stable mild-moderate COPD.

PMID- 28495075
TI  - Relationship Between Chronic Obstructive Pulmonary Disease and Air Pollutants
      Depending on the Origin and Trajectory of Air Masses in the North of Spain.
AB  - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a common respiratory
      condition and one of the leading causes of death. Our aim was to analyze the
      association between emergency room visits due to this disease and meteorological
      variables and atmospheric contaminant levels in Santander, depending on the
      origin and trajectory of air masses. METHODS: Data from emergency room visits at
      Hospital Marques de Valdecilla were collected on a daily basis during an 8-year
      period. Data on concentrations of the main atmospheric pollutants and
      meteorological variables were also recorded.Retrotrajectories leading to
      Santander at a height of1,500 meters above sea level were then calculated.
      Finally, a correlation model was produced to evaluate the effect of the
      contaminants on emergency visitsdue to COPD. RESULTS: There is a direct
      association between PM 10 levels and the number of visits to the emergency room
      due to COPD. For every 10MUg/m3 increase in pollutantlevels, emergency
      visitsincrease by3.34% (p=0.00005), and thiseffect is enhanced in individualsover
      74 years of age. This effect is heightened when PM10 levels depend on air masses
      from the South and when air recirculation occurs. There is no association
      betweenother pollutants and the number of visits to the emergency room.
      CONCLUSIONS: Exposure to high levels of PM10 causes exacerbations in COPD
      patients. By studying the atmospheric circulation pattern, we can predict whether
      PM10 levels will be inappropriately high, and we can also obtain information
      about the particle components.

PMID- 28495076
TI  - Fungal Empyema: An Uncommon Entity With High Mortality.

PMID- 28495077
TI  - Consensus on the Asthma-COPD Overlap Syndrome (ACOS) Between the Spanish COPD
      Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma
      (GEMA).
AB  - Following a proposal by the Spanish Society of Pulmonology and Thoracic Surgery
      (SEPAR), sponsor of the Spanish COPD Guidelines (GesEPOC) and the Spanish
      Guidelines on the Management of Asthma (GEMA), authors of both papers have
      unified the criteria for the diagnosis of asthma-COPD overlap syndrome (ACOS).
      This consensus defines ACOS as the presence in a given patient of three elements:
      significant smoking exposure, chronic airflow limitation and asthma. Diagnosis is
      confirmed when a patient (35years of age or older), smoker or ex-smoker of more
      than 10 pack-years, presents airflow limitation (post-bronchodilator
      FEV1/FVC<0.7) that persists after treatment with bronchodilators and inhaled
      corticosteroids (even after systemic corticosteroids in selected cases), and an
      objective current diagnosis of asthma (according to GEMA criteria). In cases in
      which the diagnosis of asthma cannot be demonstrated, marked positive results on
      a bronchodilator test (FEV1>=15% and >=400mL) or elevated blood eosinophil count
      (>=300eosinophils/MUL) will also be diagnostic of ACOS. The opinion of another 33
      experts who had not participated in the consensus was sought using a modified
      Delphi survey. Up to 80% of respondents gave a very positive opinion of the
      consensus, and declared that it was better than other previous proposals. The
      GesEPOC-GEMA consensus on ACOS provides a unique perspective of the diagnostic
      problem, using a simple proposal and a pragmatic diagnostic algorithm that can be
      applied at any healthcare level.

PMID- 28495078
TI  - Favourable effect of early versus late start of enzyme replacement therapy on
      plasma globotriaosylsphingosine levels in men with classical Fabry disease.
AB  - BACKGROUND: The level of plasma globotriaosylsphingosine (lysoGb3) is an
      indication of disease severity in Fabry disease (FD) and its decrease during
      enzyme replacement therapy could be a reflection of treatment efficacy. Early
      treatment of FD may improve clinical outcome, but data to support this hypothesis
      are scarce. In this study we compared lysoGb3 decrease after ERT initiation in
      men with classical FD who started ERT before the age of 25 (early-treatment) with
      those who started later in life (late-treatment). METHODS: Treatment naive men
      with classical FD from three centers of excellence in Europe were included.
      Measurements of lysoGb3 levels by tandem mass spectroscopy and antibodies by an
      inhibitory assay were performed in a single laboratory. Results were adjusted for
      lysoGb3 at baseline, first ERT (i.e. agalsidase alfa or beta) and the average ERT
      dose. RESULTS: 85 patients were included, 21 in the early-treatment and 64 in the
      late-treatment group. LysoGb3 level at baseline was not different between the two
      groups (112 vs 114nmol/L, p=0.92). The adjusted odds ratio for reaching a lysoGb3
      level<20nmol/L was 7.38 for the early-treatment versus late-treatment group (95%
      CI: 1.91-34.04, p=0.006). The adjusted lysoGb3 levels one year after ERT
      initiation was 12.9nmol/L lower in the early-treatment (95% CI: -20.1--5.8,
      p<0.001) compared to the late-treatment group. CONCLUSION: The current
      retrospective cohort study shows that initiation of ERT at younger age in men
      with classical Fabry disease results in a better biochemical response.

PMID- 28495079
TI  - Behavior of macroporous vinyl silica and silica monolithic columns in high
      pressure gas chromatography.
AB  - 80% vinyltrimethoxysilane-based hybrid silica monoliths (80-VTMS), which have
      been initially developed for separation in reversed-phase liquid chromatography,
      have been investigated in high pressure gas chromatography separations (carrier
      gas pressure up to 60bar) and compared to silica monolithic columns. The behavior
      of both silica and 80-VTMS monolithic columns was investigated using helium,
      nitrogen and carbon dioxide as carrier gas. The efficiency of 80-VTMS monolithic
      columns was shown to vary differently than silica monolithic columns according to
      the temperature and the carrier gas used. Carrier gas nature was a significant
      parameter on the retention for both silica and vinyl columns in relation to its
      adsorption onto the stationary phase in such high pressure conditions. The
      comparison of retention and selectivity between 80-VTMS monoliths and silica was
      performed under helium using the logarithm of the retention factor according to
      the number of carbon atoms combined to Kovats indexes. The very good performances
      of these columns were demonstrated, allowing the separation of 8 compounds in
      less than 1min.

PMID- 28495080
TI  - Determine equilibrium dissociation constant of drug-membrane receptor affinity
      using the cell membrane chromatography relative standard method.
AB  - The equilibrium dissociation constant (KD) of drug-membrane receptor affinity is
      the basic parameter that reflects the strength of interaction. The cell membrane
      chromatography (CMC) method is an effective technique to study the
      characteristics of drug-membrane receptor affinity. In this study, the KD value
      of CMC relative standard method for the determination of drug-membrane receptor
      affinity was established to analyze the relative KD values of drugs binding to
      the membrane receptors (Epidermal growth factor receptor and angiotensin II
      receptor). The KD values obtained by the CMC relative standard method had a
      strong correlation with those obtained by the frontal analysis method.
      Additionally, the KD values obtained by CMC relative standard method correlated
      with pharmacological activity of the drug being evaluated. The CMC relative
      standard method is a convenient and effective method to evaluate drug-membrane
      receptor affinity.

PMID- 28495082
TI  - Synthesis and alpha-glucosidase inhibition activity of dihydroxy pyrrolidines.
AB  - A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides
      of 3,4-dihydroxypyrrolidines as alpha-glucosidase inhibitors were designed and
      synthesized. The biological screening test against alpha-glucosidase showed that
      some of these compounds have the positive inhibitory activity against alpha
      glucosidase. Saturated aliphatic amides were more potent than the olefinic
      amides. Among all the compounds, 5o/6o having polar -NH2 group, 10f/11f having
      polar -OH group on phenyl ring displayed 3-4-fold more potent than the standard
      drugs. Acarbose, Voglibose and Miglitol were used as standard references. The
      promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified.
      Molecular docking simulations were done for compounds to identify important
      binding modes responsible for inhibition activity of alpha-glucosidase.

PMID- 28495081
TI  - Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea.
AB  - A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5
      hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3),
      together with nine known compounds (4-12) have been isolated from the active
      fractions, CHCl3 (IC50, 0.32MUgmL-1) and EtOAc (IC50, 0.55MUgmL-1) fractions of
      the leaves of Calotropis gigantea. Their structures were elucidated based on NMR
      and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent
      cytotoxicity against PANC-1 human pancreatic cancer cell line under the
      normoglycemic condition with IC50 values of 3.7 and 3.3MUM, respectively. 9'
      Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1
      cells in a concentration-dependent manner.

PMID- 28495083
TI  - Design and synthesis of potent inhibitors of the mono(ADP-ribosyl)transferase,
      PARP14.
AB  - A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were
      synthesized and tested for their ability to inhibit the mono-(ADP
      ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were
      established for this series and several compounds were identified as sub
      micromolar inhibitors of PARP14, the most potent of which was compound 4t,
      IC50=160nM. Furthermore, profiling other members of this series identified
      compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity
      over PARP10, a closely related mono-(ADP-ribosyl)transferase.

PMID- 28495084
TI  - Structural insight into the active site of mushroom tyrosinase using
      phenylbenzoic acid derivatives.
AB  - So far, many inhibitors of tyrosinase have been discovered for cosmetic and
      clinical agents. However, the molecular mechanisms underlying the inhibition in
      the active site of tyrosinase have not been well understood. To explore this
      problem, we examined here the inhibitory effects of 4'-hydroxylation and
      methoxylation of phenylbenzoic acid (PBA) isomers, which have a unique scaffold
      to inhibit mushroom tyrosinase. The inhibitory effect of 3-PBA, which has the
      most potent inhibitory activity among the isomers, was slightly decreased by 4'
      hydroxylation and further decreased by 4'-methoxylation against mushroom
      tyrosinase. Surprisingly, 4'-hydroxylation but not methoxylation of 2-PBA
      appeared inhibitory activity. On the other hand, both 4'-hydroxylation and
      methoxylation of 4-PBA increased the inhibitory activity against mushroom
      tyrosinase. In silico docking analyses using the crystallographic structure of
      mushroom tyrosinase indicated that the carboxylic acid or 4'-hydroxyl group of
      PBA derivatives could chelate with cupric ions in the active site of mushroom
      tyrosinase, and that the interactions of Asn260 and Phe264 in the active site
      with the adequate-angled biphenyl group are involved in the inhibitory activities
      of the modified PBAs, by parallel and T-shaped pi-pi interactions, respectively.
      Furthermore, Arg268 could fix the angle of the aromatic ring of Phe264, and
      Val248 is supposed to interact with the inhibitors as a hydrophobic manner. These
      results may enhance the structural insight into mushroom tyrosinase for the
      creation of novel tyrosinase inhibitors.

PMID- 28495085
TI  - Reevaluation of fenpropimorph as a sigma receptor ligand: Structure-affinity
      relationship studies at human sigma1 receptors.
AB  - Fenpropimorph (1) is considered a "super high-affinity" sigma1 receptor ligand
      (Ki=0.005nM for guinea pig sigma1 receptors). Here, we examine the binding of 1
      and several of its deconstructed analogs at human sigma1 (hsigma1) receptors. We
      monitored their subtype selectivity by determining the binding affinity at sigma2
      receptors. In addition, we validated an existing pharmacophore model at the
      molecular level by conducting 3D molecular modeling studies, using the crystal
      structure of hsigma1 receptors, and Hydrophatic INTeractions (HINT) analysis. Our
      structure affinity relationship studies showed that 1 binds with lower affinity
      at hsigma1 receptors (Ki=17.3nM) compared to guinea pig; moreover, we found that
      none of the fenpropimorph methyl groups is important for its binding at hsigma1
      receptors, nor is stereochemistry. For example, removal of all methyl groups as
      seen in 4 resulted in an almost 5-fold higher affinity at hsigma1 receptors
      compared to 1 and 350-fold selectivity versus sigma2 receptors. In addition,
      although the O atom of the morpholine ring does not contribute to affinity at
      hsigma1 receptors (and might even detract from it), it plays role in subtype
      (sigma1 versus sigma2 receptor) selectivity.

PMID- 28495086
TI  - Cell line studies and analytical measurements of three paclitaxel complex
      variations.
AB  - The copper(II) cation, sucrose, and hydroxychloroquine were complexed with the
      chemotherapy agent paclitaxel and studied for medicinal activity. Data (GI50,
      LD50) from single dose and five dose National Cancer Institute sixty cell line
      panels are presented. Analytical measurements of different complexes were made
      using Nuclear Magnetic Resonance (1H NMR), Matrix Assisted Laser Desorption
      Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) and Fourier Transform
      Ion Cyclotron Resonance (FT-ICR). Molecular modeling is utilized to better
      understand the impact that species could have on physical parameters associated
      with Lipinski's Rule of Five, such as logP and TPSA. On average, Cu(II) and
      hydroxychloroquine decreased GI50 values, while sucrose increased GI50 values of
      paclitaxel.

PMID- 28495087
TI  - Gemcitabine anti-proliferative activity significantly enhanced upon conjugation
      with cell-penetrating peptides.
AB  - Gemcitabine proven efficiency against a wide range of solid tumors and undergoes
      deamination to its inactive uridine metabolite, which underlies its low
      bioavailability, and tumour resistance was also associated with nucleoside
      transporter alterations. Hence, we have conjugated gemcitabine to cell
      penetrating peptides (CPP), in an effort to both mask its aniline moiety and
      facilitate its delivery into cancer cells. Two CPP-drug conjugates have been
      synthesized and studied regarding both the time-dependent kinetics of gemcitabine
      release and their anti-proliferative activity on three different human cancer
      cell lines. Results obtained reveal a dramatic increase in the anti-proliferative
      activity of gemcitabine in vitro, upon conjugation with the CPPs. As such, CPP
      gemcitabine conjugates emerge as promising leads for cancer therapy.

PMID- 28495088
TI  - Fluorescence guided resection with 5-aminolevulinic acid of a pilomyxoid
      astrocytoma of the third ventricle.
AB  - Fluorescence-guided resection with 5-aminolevulinic acid has been shown to be
      useful in the resection of certain brain tumors other than high grade gliomas,
      facilitating the intraoperative differentiation of neoplastic tissue. The
      technique enables the surgeon to ensure that no tumor fragments remain, thereby
      achieving higher rates of complete resection. Tihan first described pilomyxoid
      astrocytomas in 1999. They are currently classified as grade II astrocytoma
      according to the WHO classification system and, because of their tendency to
      recur and their dissemination through the cerebrospinal fluid pathways, they are
      considered to be more aggressive than pilocytic astrocytoma. As a result,
      management of these tumors must be more aggressive, always aiming for complete
      macroscopic resection whenever possible. In this article, we present a case of
      pilomyxoid astrocytoma of the third ventricle in which the use of fluorescence
      guided resection with 5-ALA facilitated complete resection. Imaging tests
      performed after five years revealed no signs of recurrence and no adjuvant
      radiotherapy or chemotherapy was required. This article also comprises a review
      of the literature concerning the characteristics and management of this tumor,
      which was recently considered to be a different histopathological entity.

PMID- 28495089
TI  - Simultaneous measurements of cations and anions using diffusive gradients in thin
      films with a ZrO-Chelex mixed binding layer.
AB  - A new method for the simultaneous measurements of eight cations [Fe(II), Mn(II),
      Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II)] and eight oxyanions [P(V),
      V(V), Cr(VI), As(III)/As(V), Se(VI), Mo(VI), Sb(V), and W(VI)] was established in
      this study using the diffusive gradients in thin films (DGT) technique with an
      improved ZrO-Chelex binding gel. The binding kinetics of each analyte in a mixed
      solution indicated a rapid uptake on the ZrO-Chelex gel. The anions exhibited
      slower absorption rates compared to the cations, which did not affect the DGT
      uptake. Stable elution efficiencies for these cations and anions were obtained
      based on a two-step extraction procedure using 1.0 M HNO3 for elution of the
      cations followed by a mixed solution containing 0.2 M NaOH and 0.5 M H2O2 for
      elution of the anions. Simultaneous measurements of the cations and anions with
      the ZrO-Chelex DGT were validated in mixed solutions and found to be independent
      of solution pH (5-9) and ionic strength (2-3 mM to 750 mM). The capacities of the
      ZrO-Chelex DGT for single measurements of Fe(II), P(V), Cd(II), As(III), and
      As(V) were determined at 99.5, 127.6, 301.2, 33.3, and 87.4 MUg cm-2. Except for
      Se(VI) in seawater, accurate measurements of all of these cations and anions in
      natural freshwater and seawater were obtained using the ZrO-Chelex DGT. The
      performance of this technique for simultaneous measurements of 16 elements was
      also tested in sediments.

PMID- 28495090
TI  - Separation of ten phosphorylated mono-and disaccharides using HILIC and ion
      pairing interactions.
AB  - Phosphorylated carbohydrates are indispensable cogs in several key metabolic
      wheels for all forms of life. Here, a straightforward liquid chromatography
      method coupled to mass spectrometry detection was developed for phosphorylated
      sugars. For separation of the targeted compounds, hydrophilic interaction
      chromatography (HILIC) was used with a bridged-ethylene hybrid amide column under
      alkaline conditions using triethylamine as a mobile phase modifier.
      Methylphosphonic acid was added to the aqueous mobile phase to reduce the tailing
      of compounds containing phosphate groups, which are known to interact with
      stainless steel components of the separation system. Under alkaline conditions
      and addition of methylphosphonic acid, the retention behavior can be attributed
      to both conventional HILIC mechanisms as well as ion-pairing interactions in the
      mobile phase. This hypothesis is supported by comparing the retention behavior of
      phosphorylated sugars and unmodified sugars. The HILIC method resolved eight
      biologically important phosphorylated sugars and thereby enables simultaneous
      detection and quantification of these compounds: fructose-1,6-bisphosphate,
      glucose-1-phosphate, glucose-6-phosphate, lactose-1-phosphate, mannose-6
      phosphate, ribose-5-phosphate, sucrose-6-phosphate, and threhalose-6-phosphate.
      Fructose-1-phosphate and fructose-6-phosphate were not resolved but
      quantification of total fructose-phosphate is possible.

PMID- 28495091
TI  - Commentary: Comments regarding Becker et al. (Analytica Chimica Acta, 835, 2014,
      1-18).

PMID- 28495092
TI  - Response-surface fits and calibration transfer for the correction of the oxygen
      effect in the quantification of carbon dioxide via FTIR spectroscopy.
AB  - During routine Fourier-Transform Infrared Spectroscopy (FTIR) based
      quantification of carbon dioxide in breath, it is necessary to account for a non
      linear signal response to the analyte concentration and disturbance factors
      arising from the gas background matrix. These factors as well as day-to-day
      fluctuation should be corrected via calibration. We present a novel strategy to
      combine the information of previous calibrations with a minimal number of actual
      calibration measurements to obtain a precise calibration. After decomposition of
      the FTIR spectra via principal component analysis (PCA) into scores
      (corresponding to intensity) and loadings (corresponding to spectral curves), an
      empirical response surface fit equation between scores, analyte concentration and
      disturbance factors is established. The fit equation can be characterized via the
      coefficients determined by calibration. Out of a pool of coefficients gained from
      several calibrations, a multivariate inter-day distribution is generated. By
      requiring the coefficient set of the actual calibration to be a sample of the
      multivariate inter-day distribution, the number of necessary routine calibration
      samples is reduced to two. The corresponding coefficients are determined using
      the Lagrange Multipliers approach and the inter-day variability of coefficients
      is estimated using Bayesian statistics and Hierarchical models. The best
      calibration parameters in terms of calibration equation, wavelength region,
      preprocessing options and choice of routine calibration samples were determined;
      optimized for minimal number of calibration samples.

PMID- 28495093
TI  - Microfabricated disposable nanosensor based on CdSe quantum dot/ionic liquid
      mediated hollow fiber-pencil graphite electrode for simultaneous electrochemical
      quantification of uric acid and creatinine in human samples.
AB  - In this research, a novel sensitive electrochemical nanosensor based on the
      cadmium selenide quantum dots (QDs)/ionic liquid mediated hollow fiber-pencil
      graphite electrode (HF-PGE) was prepared and applied for simultaneous
      determination of uric acid (UA) and creatinine (Crn) in urine and serum samples.
      The electrocatalytic oxidation of the analytes was investigated via differential
      pulse (DPV) and cyclic voltammetry (CV). The experiments were designed, in two
      different steps, according to Taguchi's method; OA9 L9 (33) and OA9 L9 (34)
      orthogonal array to optimize experimental runs. The results revealed that the
      electrode response was initially influenced by the types of sensor and types of
      ionic liquids and their ratios. The amount of QD, buffer pH, equilibration time
      and scan rate also influenced electrode response efficiency. According to the
      results of Taguchi analysis, the amount of tetra phenyl phosphonium chloride
      (TPPC) and QD were the most influencing parameters on the yield response of the
      modified electrodes. Linear ranges were obtained between 0.297-2.970 * 103 and
      0.442-8.840 * 103 MUM, with the detection limits of 0.083 and 0.229 MUM and
      relative standard deviations (RSD) of 2.4% and 1.8%, for UA and Crn,
      respectively. Finally, the proposed method was successfully examined for
      simultaneous determination of UA and Crn in human urine and serum samples.

PMID- 28495094
TI  - Determination of diclofenac using electromembrane extraction coupled with
      stripping FFT continuous cyclic voltammetry.
AB  - For the first time, on-line and ultra-sensitive determination of trace amount of
      diclofenac in whole blood sample was performed by coupling of electromembrane
      extraction (EME) and stripping fast Fourier transform continuous cyclic
      voltammetry (SFFTCCV). In SFFTCCV, the potential waveform was continuously
      applied on a carbon paste electrode and the electrode response was obtained by
      subtracting the background current and integrating the current in potential range
      of the analyte oxidation. A central composite design was used for the
      optimization of the parameters influencing the extraction efficiency. By applying
      a DC potential of 20 V during 28 min of extraction, diclofenac was migrated from
      the sample solution (pH 5), into a thin layer of 1-octanol immobilized in the
      pores of a porous flat sheet membrane and then into the acceptor solution (pH 7).
      The method presented a good linearity within the range of 5-1000 ng mL-1 with a
      determination coefficient of 0.993 in whole blood samples. Limits of detection
      (LOD) and quantification (LOQ) were found to be 1.0 ng mL-1 and 5.0 ng mL-1
      respectively.

PMID- 28495095
TI  - On-cartridge derivatisation using matrix solid phase dispersion for the
      determination of cyclamate in foods.
AB  - A novel method for determination of sodium cyclamate in foods was developed. In
      this method, a syringe was loaded with the homogeneous mixture of the sample,
      KMnO4 powder and silica dispersant and used as a matrix solid phase dispersion
      (MSPD) reactor. As the reactor was infiltrated with small amounts of concentrated
      HCl, cyclamate was converted to 2-chlorocyclohexanone quickly and effectively
      within 5 min and determined by HPLC on a reversed-phase column using UV detection
      at a wavelength of 310 nm. Comparing with the traditional derivatisation in
      solution, the better clean-up was provided using on-cartridge derivatisation of
      MSPD, and much time, labor, and expense were saved. The results showed good
      linearity (r2 = 0.9998) over the concentration range of 1-500 mg/L. The limit of
      detection (LOD) and limits of quantification (LOQ) of the cyclamate were 0.3 mg/L
      and 1 mg/L respectively. The recoveries ranged from 91.6% to 101.3% with the
      relative standard deviations (RSDs) in the range of 2.5%-4.3%.

PMID- 28495096
TI  - Sequential extraction protocol for organic matter from soils and sediments using
      high resolution mass spectrometry.
AB  - A vast number of organic compounds are present in soil organic matter (SOM) and
      play an important role in the terrestrial carbon cycle, facilitate interactions
      between organisms, and represent a sink for atmospheric CO2. The diversity of
      different SOM compounds and their molecular characteristics is a function of the
      organic source material and biogeochemical history. By understanding how SOM
      composition changes with sources and the processes by which it is
      biogeochemically altered in different terrestrial ecosystems, it may be possible
      to predict nutrient and carbon cycling, response to system perturbations, and
      impact of climate change will have on SOM composition. In this study, a
      sequential chemical extraction procedure was developed to reveal the diversity of
      organic matter (OM) in different ecosystems and was compared to the previously
      published protocol using parallel solvent extraction (PSE). We compared six
      extraction methods using three sample types, peat soil, spruce forest soil and
      river sediment, so as to select the best method for extracting a representative
      fraction of organic matter from soils and sediments from a wide range of
      ecosystems. We estimated the extraction yield of dissolved organic carbon (DOC)
      by total organic carbon analysis, and measured the composition of extracted OM
      using high resolution mass spectrometry. This study showed that OM composition
      depends primarily on soil and sediment characteristics. Two sequential extraction
      protocols, progressing from polar to non-polar solvents, were found to provide
      the highest number and diversity of organic compounds extracted from the soil and
      sediments. Water (H2O) is the first solvent used for both protocols followed by
      either co-extraction with methanol-chloroform (MeOH-CHCl3) mixture, or
      acetonitrile (ACN) and CHCl3 sequentially. The sequential extraction protocol
      developed in this study offers improved sensitivity, and requires less sample
      compared to the PSE workflow where a new sample is used for each solvent type.
      Furthermore, a comparison of SOM composition from the different sample types
      revealed that our sequential protocol allows for ecosystem comparisons based on
      the diversity of compounds present, which in turn could provide new insights
      about source and processing of organic compounds in different soil and sediment
      types.

PMID- 28495097
TI  - Workflow development for targeted lipidomic quantification using parallel
      reaction monitoring on a quadrupole-time of flight mass spectrometry.
AB  - Advances in high-resolution mass spectrometers with faster scanning capabilities
      and higher sensitivities have expanded these instruments' functionality beyond
      traditional data-dependent acquisition in targeted metabolomics. Apart from the
      traditional multiple reaction monitoring strategy, the parallel reaction
      monitoring (PRM) strategy is also used for targeted metabolomics quantification.
      The high resolution and mass accuracy of full-scan (MS1) and tandem mass
      spectrometry (MS/MS) scan result in sufficient selectivity by monitoring all
      MS/MS fragment ions for each target precursor and simultaneously providing
      flexibility in assay method construction and post-acquisition data analysis. In
      this study, using an orthogonal quadrupole-time of flight liquid chromatography
      mass spectrometry system (QTOF LC-MS), we investigated the applicability of a
      large-scale targeted lipidomic assay using scheduled PRM. This method monitored
      222 lipids belonging to 15 lipid species in serum. Robustness, reproducibility,
      and quantitative performance were assessed using chemical standards and serum
      samples. Finally, we demonstrated the application of this PRM-based targeted
      metabolomic workflow to systemic lupus erythematosus, a severe autoimmunological
      disease. Results showed that 63 lipids belonging to 11 lipid species were
      significantly changed. In summary, at the first time, a robust targeted lipidomic
      workflow was established using PRM acquisition strategy on a Q-TOF platform,
      providing another powerful tool for targeted metabolomic analysis.

PMID- 28495098
TI  - Polarization-dependent surface-enhanced Raman scattering (SERS) from microarrays.
AB  - The convergence between nanometric sensing (e.g. surface-enhanced Raman
      scattering - SERS) and lab-on-chip technologies has emerged as a potential
      revolutionary approach for a variety of "real-world" applications. Surface
      plasmons (SPs) can be excited on metal interfaces through light coupling to
      metallic surface gratings. The generation of SPs is a fundamental requirement for
      SERS. The work reported in this paper demonstrates a versatile procedure to
      prepare both large area (i.e. one inch2) and microarrays (MUarrays) metallic
      gratings structures capable of supporting SP excitation (and SERS). Laser
      interference lithography (LIL), either alone or combined with traditional laser
      photolithography (LPL), was used to generate the periodic patterns. The
      fabrication procedure was simple, high-throughput, and reproducible, with array
      to-array variations in geometrical parameters of less than 5%. Since the basic
      pattern of the nanostructures was a one-dimensional grating, the polarization
      anisotropy nature of the substrates was also explored. The use of these
      polarization-dependent properties to eliminate non-polarization sensitive
      interferences (e.g. spurious spectral background) was demonstrated. Lastly, the
      nanostructured gold MUarrays were integrated on a chip for SERS detection of ppm
      levels of 8-quinolinol, an emerging pharmaceutical contaminant in aquatic
      systems. A low-cost structure for fluid handling was realized by simply using
      perforated epoxy membranes. The results demonstrated that the procedure described
      here is suitable for the generation of simple integrated MUarrays for SERS
      applications in environmental analysis.

PMID- 28495099
TI  - A new colorimetric chemosensors for Cu2+ and Cd2+ ions detection: Application in
      environmental water samples and analytical method validation.
AB  - A new heterocyclic thiophene-2-caboxylic acid hydrazide based chemosensor R1 to
      R4 were designed, synthesized and characterized by various spectroscopic
      techniques like FT-IR, UV-Vis, 1H NMR, 13C NMR, Mass and SC-XRD. The chemosensor
      R3 showed a significant color change from colorless to yellow in the presence of
      Cu2+ ions and chemosensor R4 showed a significant color change from colorless to
      yellow in the presence of Cd2+ ions over the other tested cations such as Cr3+,
      Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Zn2+, Ag2+, Al3+, Pb2+, Hg2+, K+, Ca2+ and Mg2+.
      The high selective and sensitivity of R3 towards Cu2+ and R4 towards Cd2+ ions
      was confirmed by UV-Vis spectroscopic study. The R3 showed a red shift in the
      presence of Cu2+ ions by Deltalambdamax 67 nm and R4 showed a red shift in the
      presence of Cd2+ ions by Deltalambdamax 105 nm in the absorption spectrum. The
      binding stoichiometric ratio of the complex between R3 - Cu2+ and R4 - Cd2+ ions
      have been found to be 1:1 using the B-H plot. Under optimized experimental
      conditions, the R3 and R4 exhibits a dynamic linear absorption response range,
      from 0 to 50 MUM for Cu2+ ions and 0 to 30 MUM for Cd2+ ions, with the detection
      limit of 2.8 * 10-6 M for Cu2+ and 2.0 * 10-7 M for Cd2+ ions. The proposed
      analytical method for the quantitative determination of Cu2+ and Cd2+ ions was
      validated and successfully applied for the environmental samples with good
      precision and accuracy.

PMID- 28495100
TI  - Ultrasensitive direct competitive FLISA using highly luminescent quantum dot
      beads for tuning affinity of competing antigens to antibodies.
AB  - Herein, for the first time we report a novel direct competitive fluorescence
      linked immunosorbent assay (dcFLISA) for the ultrasensitive detection of
      ochratoxin A (OTA) by introducing a large size polymer beads loaded with quantum
      dots (QBs) as carrier of competing antigen for decreasing binding affinity to
      antibody and enhancing the fluorescent signal intensity. When using 255 nm QBs as
      carrier of competing antigen, the equilibrium dissociation constant of QB based
      competing antigen to antibodies can be tuned to 100 times higher than that of the
      horseradish peroxidase (HRP) based competing antigen by controlling labeled
      amounts of antigen on the surface of QBs. Various parameters that influenced the
      sensitivity of dcFLISA were investigated and optimized. Under optimum detection
      parameters, the dynamic linear range of developed dcFLISA for detecting OTA was
      established at 0.05 pg/mL to 1.56 pg/mL with a half maximal inhibitory
      concentration at 0.14 +/- 0.04 pg/mL (n = 5), which is three orders of magnitude
      lower than that of conventional HRP-based dcELISA (0.24 ng/mL). The developed
      FLISA is also highly accurate, reliable, and shows no cross reaction to other
      mycotoxins. In summary, the proposed method offers a straightforward approach to
      improve the sensitivity of direct competitive immunoassay for trace small
      chemical molecule detection in food quality control, environmental monitoring,
      and clinical diagnosis.

PMID- 28495101
TI  - Maternal and child health in Israel: building lives.
AB  - Israel is home to a child-oriented society that values strong family ties,
      universal child benefits, and free education for all children from 3 years of age
      to school grade 12. Alongside the universal health-care services that are
      guaranteed by the National Health Insurance Law and strong, community-based
      primary and preventive care services, these values have resulted in good maternal
      and child health. In 2015, infant and maternal mortality (3.1 deaths per 1000
      livebirths and 2.0 deaths per 100 000 livebirths, respectively) were lower than
      the mean infant and maternal mortality of countries within the Organisation for
      Economic Co-operation and Development. Israel has already exceeded the developed
      regions' Sustainable Development Goal 2030 targets for maternal mortality,
      neonatal mortality, and mortality in children younger than 5 years in all
      population groups. Yet these accomplishments are marred by Israel's high
      prevalence of child poverty (more than 30%), particularly among Arabs (63%) and
      ultra-Orthodox Jews (67%). Although infant mortality has improved in all
      subpopulations since Israel was founded in 1948, infant mortality among Arabs is
      still more than twice as high as among Jews. To address these disparities in
      health, the Israeli Ministry of Health has created a special division and has
      funded an intervention programme to reduce the infant mortality among Bedouin
      Arabs. Other interventions include targeted and culturally appropriate health
      care programmes and services for communities with a high number of at-risk
      children and young adults, dental health service for all children up to 15 years,
      and improved collaboration between health, education, and welfare services. The
      challenges faced by the Israeli health-care system include a growing trend
      towards medicalisation of prenatal care, ensuring staff are trained to treat
      developmental, behavioural, and psychosocial issues in children and their
      families, securing sustainable funding for health promotion and injury prevention
      programmes, expanding and improving the coordination of services for children
      with special needs or who are at risk, and programme assessment. Ensuring
      adequate funding for dedicated, preventive paediatric care and taking action on a
      nationwide scale to reduce child poverty are essential for maintaining health
      gains in children. In this Series paper, we describe the health indices,
      highlight disparities, and discuss the challenges in delivering and maintaining
      maternal and child health care in Israel.

PMID- 28495102
TI  - Dr David Nabarro is the best candidate for WHO Director-General.

PMID- 28495103
TI  - Orly Manor: public health leader in Israel's health system.

PMID- 28495104
TI  - Rafael Beyar: a meeting of medicine, science, and technology.

PMID- 28495105
TI  - Digital health nation: Israel's global big data innovation hub.

PMID- 28495106
TI  - Israel: health and beyond.
AB  - The principle that global human identity and dignity supersede other values is a
      broadly accepted conviction that guides practice and policies in the realm of
      human health in most of the world. An assessment of the level of success that
      Israel has achieved in health, in the face of formidable challenges, including
      rapid population growth, diverse and often divided ethnic affiliations, and
      existential security threats, leads us to propose that extension of this
      principle of global human identity and dignity, together with the objective of a
      decent society, as overriding values beyond health to other domains of human
      endeavour within Israel and in its relations with neighbouring peoples,
      represents an entirely achievable imperative. The result will be to further
      advance Israel's aspiration to serve as a model for societal decency with wide
      international acceptance and engagement. We have identified several determinants
      of Israel's advancement in health, including: articulation of a clear vision,
      national purpose, and long-term commitment that seeks to take the health of its
      citizens seriously; a multi-ethnic population that brings diversity and energy to
      national progress; a political democracy, which is characterised by robust debate
      and discussion about the nation's future; national legislation governing cardinal
      health-care processes; cultural and religious histories that respect and revere
      scholarship, learning, research, and charitable donation; an expanding economy,
      with recent but increasing appreciation of the economic, social, and political
      underpinnings of health and health inequalities; a strong base of international
      support from the Diaspora Jewish community; and a strong desire for acceptance by
      the international community in key arenas, especially science and health. As a
      result, despite the fewer than seven decades since its establishment, Israel has
      achieved important milestones in health. Nevertheless, this trajectory of
      achievement is threatened by several serious challenges, including the capacity
      to sustain high-quality universal health coverage, especially for an ageing
      population living with multiple comorbidities in the face of a stagnant level of
      the percentage of treasury funding to health care at a level that is well below
      the average of the Organisation for Economic Co-operation and Development; ever
      increasing transfer of services and care covered by the mandatory public health
      services basket to private programmes; insufficient progress in resolving health
      disparities among and between communities, populations, and regions of the
      country congruent with disparities in income and employment; gender inequities; a
      looming increase in the already alarming shortfall in health-care professionals;
      and failure to match inpatient and acute care facilities to manage growing needs.
      These challenges within Israel are magnified in the context of health disparities
      with the neighbouring Palestinian population, a situation in which ongoing-but
      fragile and limited-health cooperation and training arrangements cannot stand in
      for a solution that will address Palestinian national aspirations. We come away
      from this Series with a great sense of optimism, but with specific
      recommendations that are based on the foregoing challenges. We believe that by
      increasing the investment in the health sector, which includes investing in the
      societal, political, educational, and environmental underpinnings of health, far
      more can be achieved to move Israel to a model international leadership position
      in health care, education, and research, and turn health into an engine for
      economic wellbeing and development. Religious leadership in Israel, with its
      formidable political influence, can be harnessed to promote health initiatives in
      areas ranging from smoking cessation and healthy diet to organ transplantation,
      and most of all condemnation of hostility and its replacement by peaceful
      resolution of even the deepest conflicts. Most of all, this Series showed that
      there is an enormous opportunity, which Israel can lead, to leverage the
      universally accepted principles of health as a sanctuary against conflict and
      inequity, to achieve a brighter future for a deeply troubled region of the world.

PMID- 28495107
TI  - Helping hands across a war-torn border: the Israeli medical effort treating
      casualties of the Syrian Civil War.

PMID- 28495108
TI  - Medical genetics in Israel's diverse population.

PMID- 28495109
TI  - Health and health care in Israel: an introduction.
AB  - Starting well before Independence in 1948, and over the ensuing six decades,
      Israel has built a robust, relatively efficient public system of health care,
      resulting in good health statistics throughout the life course. Because of the
      initiative of people living under the British Mandate for Palestine (1922-48),
      the development of many of today's health services predated the state's
      establishment by several decades. An extensive array of high-quality services and
      technologies is available to all residents, largely free at point of service, via
      the promulgation of the 1994 National Health Insurance Law. In addition to a
      strong medical academic culture, well equipped (albeit crowded) hospitals, and a
      robust primary-care infrastructure, the country has also developed some model
      national projects such as a programme for community quality indicators, an annual
      update of the national basket of services, and a strong system of research and
      education. Challenges include increasing privatisation of what was once largely a
      public system, and the underfunding in various sectors resulting in, among other
      challenges, relatively few acute hospital beds. Despite substantial
      organisational and financial investment, disparities persist based on ethnic
      origin or religion, other socioeconomic factors, and, regardless of the country's
      small size, a geographic maldistribution of resources. The Ministry of Health
      continues to be involved in the ownership and administration of many general
      hospitals and the direct payment for some health services (eg, geriatric
      institutional care), activities that distract it from its main task of planning
      for and supervising the whole health structure. Although the health-care system
      itself is very well integrated in relation to the country's two main ethnic
      groups (Israeli Arabs and Israeli Jews), we think that health in its widest sense
      might help provide a bridge to peace and reconciliation between the country and
      its neighbours.

PMID- 28495110
TI  - Women and health in Israel.

PMID- 28495111
TI  - Medical ethics in Israel-bridging religious and secular values.

PMID- 28495112
TI  - Inequalities in non-communicable diseases between the major population groups in
      Israel: achievements and challenges.
AB  - Israel is a high-income country with an advanced health system and universal
      health-care insurance. Overall, the health status has improved steadily over
      recent decades. We examined differences in morbidity, mortality, and risk factors
      for selected non-communicable diseases (NCDs) between subpopulation groups.
      Between 1975 and 2014, life expectancy in Israel steadily increased and is
      currently above the average life expectancy for the Organisation for Economic Co
      operation and Development countries. Nevertheless, life expectancy has remained
      lower among Israeli Arabs than Israeli Jews, and this gap has recently widened.
      Age-adjusted mortality as a result of heart disease, stroke, or diabetes remains
      higher in Arabs, whereas age-adjusted incidence and mortality of cancer were
      higher among Jews. The prevalence of obesity and low physical activity in Israel
      is considerably higher among Arabs than Jews. Smoking prevalence is highest for
      Arab men and lowest for Arab women. Health inequalities are also evident by the
      indicators of socioeconomic position and in subpopulations, such as immigrants
      from the former Soviet Union, ultra-Orthodox Jews, and Bedouin Arabs. Despite
      universal health coverage and substantial improvements in the overall health of
      the Israeli population, substantial inequalities in NCDs persist. These
      differences might be explained, at least in part, by gaps in social determinants
      of health. The Ministry of Health has developed comprehensive programmes to
      reduce these inequalities between the major population groups. Sustained
      coordinated multisectoral efforts are needed to achieve a greater impact and to
      address other social inequalities.

PMID- 28495113
TI  - The medical education system in Israel.

PMID- 28495115
TI  - A personal perspective on health in Israel.

PMID- 28495114
TI  - Coming of age: health-care challenges of an ageing population in Israel.
AB  - Although Israel is still young in years, with relatively high birth rates and
      older people (individuals aged 65 years or older) constituting only about 11% of
      its population, the absolute number of older people is growing rapidly. Life
      expectancy is high, and increasing numbers of people are living to advanced old
      age (older than 85 years). A wide spectrum of geriatric care is provided within a
      universal system providing health services to all citizens. Community and
      institutional care is available, and many innovative programmes are being
      developed. The unique demographic characteristics of the ageing society in Israel
      reflect cultural and multiethnic diversity, in addition to a high rate of
      immigration of older people. To meet the growing challenges, address disparities,
      and search for innovation will require planning and development of adequate
      services at the highest level.

PMID- 28495116
TI  - Israel: a start-up life science nation.

PMID- 28495117
TI  - First experience with the Watchman FLX occluder for percutaneous left atrial
      appendage closure.
AB  - BACKGROUND: We aimed to evaluate efficacy and safety of left atrial appendage
      (LAA) closure with the new Watchman FLX and analyze procedural features in a
      consecutive series of high risk non-valvular atrial fibrillation patients.
      METHODS AND RESULTS: Twelve consecutive non-valvular atrial fibrillation patients
      (age 76.6+/-7.8years) at high risk for stroke (CHA2DS2-VASc-Score 5.5+/-0.9) and
      bleeding (HAS-BLED-Score 3.8+/-0.9), received LAA closure with the Watchman FLX.
      Bench testing demonstrated easy repositioning as well as optimized sealing and
      anchoring. Follow-up was done at 30days, and at 3 and 6months including
      transesophageal echocardiography after 3months. Compression was calculated as
      occluder size to diameter at shoulder in final position. The device was
      successfully implanted in all patients. Partial recapture was necessary in 6
      (50%) of cases, and full recapture in one (8.3%). There were no procedure-related
      complications. In 83.3% of cases (N=10/12) compression was between 10 and 27%,
      and mean compression was 24.0+/-11.1%. Mean implantation depth was 4.0+/-4.4mm
      distal of LAA ostium. There was no residual flow. Proximal shift in device
      position was noticed in 2 patients. One device was embolized at 30day follow-up,
      and another device showed thrombus formation. There was no disabling or non
      disabling stroke through 6months of follow-up with dual antiplatelet therapy for
      3months. CONCLUSION: LAA closure with the new Watchman FLX is associated with a
      good periprocedural safety, complete sealing of the LAA and simple repositioning.
      SUMMARY: We evaluated the efficacy and safety of left atrial appendage (LAA)
      closure with the new Watchman FLX and analyzed procedural features in a
      consecutive series of high risk non-valvular atrial fibrillation patients. This
      is a first observational study demonstrating procedural safety, complete sealing
      of the LAA and simple technique for repositioning. There was no stroke within a
      6month follow-up.

PMID- 28495118
TI  - Complication of descompressive craniectomy: An early "syndrome of the trephined".

PMID- 28495119
TI  - Toll-like receptor 3 mediates UVB-induced MMP-13 and MMP-3 expressions in mice.

PMID- 28495120
TI  - Combined treatment with H1 and H4 receptor antagonists reduces inflammation in a
      mouse model of atopic dermatitis.
AB  - BACKGROUND: Histamine 4 receptor (H4R) antagonists are considered as new
      therapeutics for the treatment of atopic dermatitis (AD) and first clinical
      trials have already shown promising results. Histamine 1 receptor (H1R)
      antagonists are traditionally used to treat AD although the evidence for the
      efficacy is weak. The combined blockade of both, H1R and H4R, might provide
      synergistic anti-inflammatory. OBJECTIVE: The study was performed to test the
      anti-inflammatory potential of a combined treatment with an H1R and an H4R
      antagonist in a mouse AD model. METHODS: The development of ovalbumin-induced AD
      like skin lesions was analysed mice treated with the H1R inverse agonist
      mepyramine, the H4R antagonist JNJ-39758979 or a combination of both. RESULTS:
      Mice treated with mepyramine plus JNJ-39758979 showed less severe skin lesions,
      with a diminished influx of inflammatory cells, a reduced epidermal thickening
      and a lower level of IL-33 in lesional skin. Scratching behaviour was ameliorated
      in mice treated with the combination. Moreover, total numbers of skin-draining
      lymph node cells and splenocytes were significantly reduced. Both substances
      given alone did not elicit this strong anti-inflammatory effect. CONCLUSION: H1R
      and H4R antagonists provide synergistic anti-inflammatory effects in a mouse
      model of AD. The combined therapy with H1R and H4R antagonists might represent a
      new strategy for the treatment of AD.

PMID- 28495121
TI  - Approaches to appropriate care delivery from a policy perspective: A case study
      of Australia, England and Switzerland.
AB  - BACKGROUND: Appropriateness is a conceptual way for health systems to balance
      Triple Aim priorities for improving population health, containing per capita
      cost, and improving the patient experience of care. Comparing system approaches
      to appropriate care delivery can help health systems establish priorities and
      facilitate appropriate care practices. METHODS: We conceptualized system
      appropriateness by identifying policies that aim to achieve the Triple Aim and
      their consequent trade-offs for financing, clinical practice, and the individual
      patient. We used secondary data sources to compare the appropriate care
      approaches of Australia, England, and Switzerland according to financial,
      clinical, and individual appropriateness policies. FINDINGS: Health system
      approaches to appropriate care delivery varied. England prioritizes public
      health, equity and efficiency at the expense of individual choice, while
      Switzerland focuses on individual patient preferences, but has higher per capita
      and out of pocket costs. Australia provides equity in public care access and
      private health care options that allows for more patient choice, with health care
      costs falling between the two. CONCLUSIONS: Integrating the Triple Aim into
      health system design and policy can facilitate appropriate care delivery at the
      system, clinical, and individual levels. Approaches will vary and require
      countries to negotiate and justify priorities and trade-offs within the context
      of thehealth system.

PMID- 28495123
TI  - In Response to "Hypothermia for Neuroprotection in Convulsive Status
      Epilepticus".

PMID- 28495122
TI  - Next Generation Sequencing uncovers within-host differences in the genetic
      diversity of Cryptosporidium gp60 subtypes.
AB  - The extent of within-host genetic diversity of parasites has implications for our
      understanding of the epidemiology, disease severity and evolution of parasite
      virulence. As with many other species, our understanding of the within-host
      diversity of the enteric parasite Cryptosporidium is changing. The present study
      compared Sanger and Next Generation Sequencing of glycoprotein 60 (gp60)
      amplicons from Cryptosporidium hominis (n=11), Cryptosporidium parvum (n=22) and
      Cryptosporidium cuniculus (n=8) DNA samples from Australia and China. Sanger
      sequencing identified only one gp60 subtype in each DNA sample: one C. hominis
      subtype (IbA10G2) (n=11), four C. parvum subtypes belonging to IIa (n=3) and IId
      (n=19) and one C. cuniculus subtype (VbA23) (n=8). Next Generation Sequencing
      identified the same subtypes initially identified by Sanger sequencing, but also
      identified additional gp60 subtypes in C. parvum and C. cuniculus but not in C.
      hominis, DNA samples. The number of C. parvum and C. cuniculus subtypes
      identified by Next Generation Sequencing within individual DNA samples ranged
      from two to four, and both C. parvum IIa and IId subtype families were identified
      within the one host in two samples. The finding of the present study has
      important implications for Cryptosporidium transmission tracking as well as
      vaccine and drug studies.

PMID- 28495124
TI  - Using visual demonstrations in young adults to promote smoking cessation:
      Preliminary findings from a French pilot study.
AB  - BACKGROUND: A personalised, smoking cessation message was successfully delivered
      in Australian community pharmacies to motivate behavioural change in young
      smoking adults. OBJECTIVE: The purpose of this pilot study was to test the
      acceptability and effectiveness of the innovative, proven smoking cessation
      intervention to another population of young adults with a higher prevalence of
      smoking and associated morbidities. METHODS: Ninety eight university students in
      Paris, France were recruited to a pilot study (50 intervention: 48 control). All
      students received smoking cessation counselling sessions and half also received a
      visual demonstration of themselves, both as a lifelong smoker and non-smoker.
      RESULTS: There was no statistical significant difference between the groups in
      smoking dependence at recruitment. At the three month follow-up, the proportion
      who had attempted to quit smoking were 37% (control) vs 46% (intervention). These
      percentages suggested a positive result for the intervention, although the
      difference was not statistically significant (p = 0.39). CONCLUSION: This is one
      of the first studies conducted in France using visual demonstrations combined
      with healthcare counselling to promote smoking cessation amongst young adult
      smokers. Further research, recruiting from the general French public, is needed
      to better understand if the innovative personalised health message can motivate
      young French adult smokers to quit.

PMID- 28495125
TI  - Comparative study of presurgical hand hygiene with hydroalcoholic solution versus
      traditional presurgical hand hygiene.
AB  - OBJECTIVE: To compare presurgical hand hygiene with hydroalcoholic solution
      following the WHO protocol with traditional presurgical hand hygiene. METHODS:
      Cultures of the hands of surgeons and surgical nurses were performed before and
      after presurgical hand hygiene and after removing gloves at the end of surgery.
      Cultures were done in 2different days: the first day after traditional
      presurgical hand hygiene, and the second day after presurgical hand hygiene with
      hydroalcoholic solution following the WHO protocol. The duration of the
      traditional hand hygiene was measured and compared with the duration (3min) of
      the WHO protocol. The cost of the products used in the traditional technique was
      compared with the cost of the hydroalcoholic solution used. The variability of
      the traditional technique was determined by observation. RESULTS: Following
      presurgical hand hygiene with hydroalcoholic solution, colony-forming units (CFU)
      were detected in 5 (7.3%) subjects, whereas after traditional presurgical hand
      hygiene CFU were detected in 14 subjects (20.5%) (p < 0.05). After glove removal,
      the numbers of CFU were similar. The time employed in hand hygiene with
      hydroalcoholic solution (3min) was inferior to the time employed in the
      traditional technique (p < 0.05), its cost was less than half, and there was no
      variability. CONCLUSIONS: Compared with other techniques, presurgical hand
      hygiene with hydroalcoholic solution significantly decreases CFU, has similar
      latency time, a lower cost, and saves time.

PMID- 28495126
TI  - Recanalisation of Bronchial Venous Plexuses in Superior Venous Cava Occlusion.

PMID- 28495127
TI  - Spontaneous Regression of a Gigantic Cardiac Rhabdomyoma.

PMID- 28495128
TI  - Ulcerative nodules on the perineum.

PMID- 28495129
TI  - [Generic drugs controversy in oncology].

PMID- 28495130
TI  - Prognostic value of oligoclonal IgG bands in Japanese clinically isolated
      syndrome converting to clinically definite multiple sclerosis.
AB  - We evaluated the impact of brain MRI findings and oligoclonal IgG bands (OCBs) on
      conversion to clinically definite multiple sclerosis (CDMS) in 26 Japanese
      patients with clinically isolated syndrome (CIS). 19.2% had OCBs positivity and
      3.8% had fulfillment of Barkhof criteria at baseline. 60.0% of CIS patients with
      positive OCBs and 9.5% of those with negative OCBs developed CDMS during
      60.6months. Japanese CIS patients with positive OCBs have an equivalent risk of
      developing CDMS. A hypothesis that Japanese CIS patients may have substantially
      less OCBs positivity, MRI lesions, and conversion ratio than Caucasians, should
      be further tested.

PMID- 28495131
TI  - Massive intracerebral Epstein-Barr virus reactivation in lethal multiple
      sclerosis relapse after natalizumab withdrawal.
AB  - Rebound of disease activity in multiple sclerosis patients after natalizumab
      withdrawal is a potentially life-threatening event. To verify whether highly
      destructive inflammation after natalizumab withdrawal is associated with Epstein
      Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage
      cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient
      who died during a fulminating MS relapse following natalizumab withdrawal.
      Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white
      matter lesions; the highest frequency of EBV lytically infected cells and
      granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These
      results may encourage switching to B-cell depleting therapy after natalizumab
      discontinuation.

PMID- 28495132
TI  - Predicting the effects of potentially therapeutic modified peptides on polyclonal
      T cell populations in a mouse model of multiple sclerosis.
AB  - Altered peptide ligands (APLs) have routinely been studied in clonal populations
      of Th cells that express a single T cell receptor (TCR), but results generated in
      this manner poorly predict the effects of APLs on polyclonal Th cells in vivo,
      contributing to the failure of phase II clinical trials of APLs in autoimmune
      diseases such as multiple sclerosis (MS). We have used a panel of APLs derived
      from an encephalitogenic epitope of myelin proteolipid protein to investigate the
      relationship between antigen cross-reactivity in a polyclonal environment,
      encephalitogenicity, and the capacity of an APL to provide protection against
      experimental autoimmune encephalomyelitis (EAE) in SJL mice. In general,
      polyclonal Th cell lines specific for encephalitogenic APLs cross-reacted with
      other encephalitogenic APLs, but not with non-encephalitogenic APLs, and vice
      versa. This, alongside analysis of TCR Vbeta usage, suggested that
      encephalitogenic and non-encephalitogenic subgroups of APLs expand largely non
      cross-reactive Th cell populations. As an exception to the rule, one non
      encephalitogenic APL, L188, induced proliferation in polyclonal CD4+ T cells
      specific for the native encephalitogen, with minimal induction of cytokine
      production. Co-immunization of L188 alongside the native encephalitogen slightly
      enhanced disease development. In contrast, another APL, A188, which induced IL-10
      production without proliferation in CD4+ T cells specific for the native
      encephalitogen, was able to protect against development of EAE in a dose
      dependent fashion when co-immunized alongside the native encephalitogen. These
      results suggest that testing against polyclonal Th cell lines in vitro may be an
      effective strategy for distinguishing between potentially therapeutic and non
      therapeutic APLs.

PMID- 28495134
TI  - Reevaluating the role of IDO1: Examining NAD+ metabolism in inflammation.

PMID- 28495133
TI  - Multiple sclerosis in India: Iceberg or volcano.
AB  - Multiple sclerosis (MS)1 is a chronic neurodegenerative disease involving
      destruction of the myelin sheath around axons of the brain, spinal cord and optic
      nerve. There has been a tremendous transformation in its perspective across
      globe. In recent years, its prevalence has changed dramatically worldwide and
      India is no exception. Initially, MS was believed to be more common in the
      Caucasians of Northern Europe and United States; however, it has been found to be
      present in Indian subcontinent as well. There has been a considerable shift in MS
      prevalence in India and this has really changed the notion of considering India
      as a low risk zone for MS. In this review, a concise overview and latest update
      on changing scenario of MS in India is presented along with some major challenges
      regarding it persisting across globe even today. In India, remarkable upsurge is
      needed in carrying out large scale population-based epidemiological studies to
      get an idea about the true incidence and prevalence rates of MS viz a viz disease
      burden. Through this review, we have probably tried to identify the actual
      picture of MS prevalence in India and this could serve as harbinger for upcoming
      research and at the same time it would definitely aid in working out future
      strategies for MS management in the country.

PMID- 28495135
TI  - Inflammatory cytokines and functional impairment in drug-free subjects with mood
      disorder.
AB  - OBJECTIVE: To assess the association between peripheral levels of inflammatory
      cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major
      Depressive Disorder (MDD) and population controls. METHODS: This was a cross
      sectional study with a matched sample of drug-free young adults with BD (n=48),
      MDD (n=48) and population controls (n=48). Mood disorder was confirmed by a
      certified psychologist using the Structured Clinical Interview for DSM-IV (SCID
      I). Functional impairment was assessed using the Functional Assessment Short Test
      (FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. RESULTS:
      Peripheral levels of IL-6 and IL-10 were not significantly different between
      subjects with BD, MDD compared to controls. Higher levels of functional
      impairment were verified in subjects with BD and MDD compared to population
      controls (p<=0.001). In addition, IL-6 and IL-10 levels were positively
      correlated with functional impairment in subjects with BD (IL-6: r=0.349,
      p=0.016; and IL-10: r=0.351, p=0.016). CONCLUSION: Inflammatory dysregulation was
      associated with functional impairment among drug-free subjects with BD. This
      finding suggests that inflammatory dysregulation may be involved in the
      neuroprogression of BD.

PMID- 28495137
TI  - Early predictors of rapidly evolving multiple sclerosis: A case report.
AB  - : Objective The aim of this case report is to highlight some important features
      of rapidly evolving Multiple Sclerosis. BACKGROUND: In a small proportion of
      patients, Multiple Sclerosis (MS) can present as a fulminant disease
      characterised by severe and frequent relapses. This form of rapidly evolving MS
      is associated with significant morbidity and mortality. It is therefore important
      to identify these patients as early as possible, so that they can be managed
      effectively. However, due to the rarity of fulminant forms of MS, there is
      limited data on the natural history and management of this condition. CASE
      REPORT: We present a young man with rapidly evolving Multiple Sclerosis (MS) who
      had 2 disabling relapses within 14weeks. He had an unusually high CSF white cell
      count at presentation (86per mm3; 100% lymphocytes, 97% T cells, 3% B cells),
      with positive oligoclonal bands. Brain MRI showed large, cavitating lesions, with
      no enhancement. He required a prolonged course of intravenous methyl-prednisolone
      and plasma exchange. CONCLUSIONS: This case suggests that male gender, young age
      at onset, time to second relapse, relapse severity, high CSF white cell count at
      presentation, large and cavitating lesions on MRI may be early predictors of
      rapidly evolving MS. It also highlights the therapeutic value of plasma exchange
      and longer courses of intravenous methylprednisolone in managing severe MS
      relapses. Enhancement may not always be a reliable indicator of disease activity,
      particularly in clinical settings where single dose gadolinium is used, due to
      its low sensitivity in detecting blood brain barrier leakage.

PMID- 28495136
TI  - Heritability of plasma neopterin levels in the Old Order Amish.
AB  - BACKGROUND: We examined the heritability of neopterin, a biomarker for cell
      mediated immunity and oxidative stress, and potentially for psychiatric
      disorders, in the Old Order Amish. METHODS: Plasma neopterin levels were
      determined in 2015 Old Order Amish adults. Quantitative genetic procedures were
      used to estimate heritability of neopterin. RESULTS: Heritability of log
      neopterin was estimated at 0.07 after adjusting for age, gender, and household
      (p=0.03). The shared household effect was 0.06 (p<0.02). CONCLUSIONS: We found a
      low heritability of neopterin and small household effect, suggesting that non
      household environmental factors are more important determinants of variance of
      neopterin levels in the Amish.

PMID- 28495138
TI  - Effect of ethnic origin and gender on the clinical manifestations of myasthenia
      gravis among the Jewish population in Israel.
AB  - Reports on patients with myasthenia gravis (MG) of different ethnic origins
      demonstrated differences in weakness distribution and serological results. We
      studied MG characteristics in a cohort of Ashkenazi (ASH) and non-Ashkenazi
      (NASH) Jewish origin according to their ethnic origins and gender. The frequency
      of age of MG onset was distributed in a bi-modal fashion in the female patients
      and increased gradually over time, with a peak around 70years of age in the male
      patients. Ocular MG was more frequent in males and ASH patients. Unlike previous
      reports, our male patients had a higher proportion of positive serum anti-acetyl
      choline receptor (AChR) than female patients, with no ethnic-based differences in
      the rates of anti-AChR or anti-muscle specific kinase. Comorbidity with another
      autoimmune disease was more frequent among female patients with late-onset MG and
      NASH patients (mainly Israel-born). Male MG patients tended to have more
      malignant comorbidities than female MG patients. These results demonstrate the
      effect of ethnicity on clinical aspects of MG within the Jewish population in
      Israel, and reveal novel effects of gender-associated comorbidities in patients
      with MG.

PMID- 28495139
TI  - High yield primary microglial cultures using granulocyte macrophage-colony
      stimulating factor from embryonic murine cerebral cortical tissue.
AB  - BACKGROUND: Microglia play vital roles in neurotrophic support and modulating
      immune or inflammatory responses to pathogens or damage/stressors during disease.
      This study describes the ability to establish large numbers of microglia from
      embryonic tissues with the addition of granulocyte-macrophage stimulating factor
      (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo
      as well as their responses to inflammatory mediators. METHOD: Microglia were
      seeded from a primary embryonic mixed cortical suspension with the addition of GM
      CSF. Microglial expression of CD45, CD11b, CD11c, MHC class I and II, CD40, CD80,
      and CD86 was analyzed by flow cytometry and compared to those isolated using
      different culture methods and to the BV-2 cell line. GM-CSF microglia
      immunoreactivity and cytokine production was examined in response to
      lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). RESULTS: Our results
      demonstrate GM-CSF addition during microglial culture yields higher cell numbers
      with greater purity than conventionally cultured primary microglia. We found that
      the expression of immune markers by GM-CSF microglia more closely resemble adult
      microglia than other methods or an immortalized BV-2 cell line. Primary
      differences amongst the different groups were reflected in their levels of CD39,
      CD86 and MHC class I expression. GM-CSF microglia produce CCL2, tumor necrosis
      factor-alpha, IL-6 and IL-10 following exposure to LPS and alter costimulatory
      marker expression in response to LPS or IFN-gamma. Notably, GM-CSF microglia were
      often more responsive than the commonly used BV-2 cell line which produced
      negligible IL-10. CONCLUSION: GM-CSF cultured microglia closely model the
      phenotype of adult microglia examined ex vivo. GM-CSF microglia are robust in
      their responses to inflammatory stimuli, altering immune markers including Iba-1
      and expressing an array of cytokines characteristic of both pro-inflammatory and
      reparative processes. Consequently, the addition of GM-CSF for the culturing of
      primary microglia serves as a valuable method to increase the potential for
      studying microglial function ex vivo.

PMID- 28495140
TI  - Multiple sclerosis risk pathways differ in Caucasian and Chinese populations.
AB  - Large-scale genome-wide association study (GWAS) datasets provide strong support
      for investigations of the mechanisms underlying multiple sclerosis (MS) by using
      pathway analysis methods. In our recent study, we conducted a three-stage pathway
      analysis of GWAS and expression datasets. After identifying 15 shared MS pathways
      in separate MS GWAS datasets, we found that dysregulated MS genes were
      significantly enriched in 10 of the 15 MS risk pathways. Evidence showed that 17%
      30% of genes are differentially expressed among individual ethnic populations. We
      then verified the potential disruption of genes in the 10 MS risk pathways cited
      above in Chinese MS patients. Here, we investigated potential up- and down
      regulation of 42 MS genes in these 10 MS risk pathways using 132 Chinese MS
      patients and 76 healthy control subjects. We then identified 31 differentially
      expressed genes in Chinese MS patients compared to healthy control subjects.
      Moreover, the expression patterns of 28 of these genes were consistent with those
      obtained from Caucasian (European and American) MS patients, although 14 genes
      differed from the latter group's. Our results provide clinically useful clues
      about the link between these risk genes and MS susceptibility in the Chinese
      population.

PMID- 28495141
TI  - Association of lower serum Brain-derived neurotrophic factor levels with larger
      infarct volumes in acute ischemic stroke.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays a potential role in
      stroke recovery, as it promotes plasticity. The aim of this study is to
      investigate the association between infarct volume using DWI and BDNF at
      admission in patients with acute ischemic stroke (AIS). METHODS: The study
      population comprised consecutive patients with an AIS diagnosis who had been
      referred to our hospital between January 2015 and June 2016. The severity of
      stroke was evaluated by the National Institutes of Health Stroke Scale (NIHSS) at
      admission. Infarct volumes indicated by DWI were measured with MIPAV software.
      The relationship between median DWI infarct volume and serum BDNF level quartiles
      was evaluated using a semiparametric approach with univariate and multivariate
      quartile regression analysis. RESULTS: In this study, 270 patients were included
      and met the study criteria. The median DWI infarct volumes for the serum BDNF
      level quartiles (lowest to highest) were 10.56, 5.13, 3.75 and 2.43ml.
      Nonparametric Spearman rank correlation revealed a statistically significant
      negative correlation between serum BDNF level and DWI infarct volume (r=-0.363;
      P<0.001). The median DWI infarct volume in the lowest BDNF quartile was
      significantly larger than those in the upper 3 quartiles (P<0.001). Further,
      median adjusted DWI infarct volumes (IQR) for each of the BDNF level quartiles
      were 7.77, 4.56, 3.75, and 2.43ml from lowest to highest quartiles. CONCLUSIONS:
      Larger stroke infarct volumes using DWI are associated with lower levels of BDNF
      at admission. Further investigations are suggested to elucidate the role of BDNF
      as part of a potential neuroprotective strategy.

PMID- 28495142
TI  - N-methyl-d-aspartate receptor-mediated calcium overload and endoplasmic reticulum
      stress are involved in interleukin-1beta-induced neuronal apoptosis in rat
      hippocampus.
AB  - Increased levels of interleukin (IL)-1beta and its gene expression are implicated
      in the etiology of Alzheimer's disease (AD). IL-1beta activates microglia and
      stimulates glutamatergic N-methyl-d-aspartate receptor NMDA receptor expression,
      thereby disturbing intracellular Ca2+ homeostasis. Ca2+ disequilibrium, in turn,
      may trigger endoplasmic reticulum (ER) stress, contributing to overall
      excitotoxicity and neuronal death that evoke AD. However, it is unclear whether
      IL-1beta-induced neuronal apoptosis is mediated by the glutamatergic system, ER
      stress and/or Ca2+ dysfunction. The present study investigated the role of NMDA
      receptor (NMDAR) in ER stress and IL-1beta-evoked neuronal death by assessing
      NMDAR-induced Ca2+ overload and NMDA-mediated ER stress. Male Long Evans rats
      were treated with IL-1beta (with or without NMDAR antagonist MK801) injected
      intracerebroventricularly for 8days. Glutamate concentration was measured by
      HPLC, and mRNA and protein expression of microglial biomarkers and NMDAR, as well
      as markers of Ca2+ overload (caplain2) and ER stress (glucose-regulated protein
      78, GRP78, and C/EBP homologous protein-10, CHOP), were assessed by real-time PCR
      and western blot. Apoptosis was also evaluated in the hippocampal neurons using
      TUNEL. Overall, IL-1beta induced robust neuronal apoptosis, accompanied by
      upregulated NMDAR, caplain2, GRP78 and CHOP. MK801 pretreatment significantly
      attenuated neuronal apoptosis and NMDA up-regulation, also reducing GRP78 and
      CHOP expression. In summary, these results suggest that IL-1beta may disturb
      intracellular Ca2+ homeostasis via NMDAR-mediated mechanism, thereby triggering
      neuronal apoptosis by enhancing ER stress.

PMID- 28495143
TI  - Central and peripheral nervous system immune-mediated demyelinating disease after
      allogeneic hematopoietic stem cell transplantation.
AB  - OBJECTIVE: We aimed to evaluate clinical and diagnostic features of central and
      peripheral immune-mediated demyelinating disease (CPID) in allogeneic
      hematopoietic stem cell transplantation (aHSCT) recipients. BACKGROUND: CPID
      refers to the late-onset, immune-mediated neurological complications following
      aHSCT, when other frequent differential diagnoses have been ruled out, and when
      symptoms and signs of systemic GvHD manifestations are absent. METHODS: Case
      records at the University of Tuebingen, between 2001 and 2015, were screened to
      identify patients with CPID after aHSCT. RESULTS: Seven patients who developed
      CPID after aHSCT were identified. The average time interval from aHSCT until
      onset of CPID was 2.6 (+/-2.8) years (mean+/-SD). The most prevalent
      manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy.
      Cerebrospinal fluid analyses involved elevated protein concentration and
      lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were
      detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI
      studies showed features suggestive of demyelination processes, with cerebral
      and/or spinal cord white-matter involvement, and features compatible with
      cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide,
      Rituximab and Interferon beta-1a showed marginal treatment responses, whereas
      plasma exchange resulted in marked clinical improvement in two treated patients.
      A chronic disease-course with persisting neurological deficits was prevalent.
      CONCLUSIONS: CPID may comprise a rare complication of aHSCT, which manifests as
      optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy.
      A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis.
      Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical
      awareness is required, as early diagnosis and aggressive treatment may be
      prognostically advantageous.

PMID- 28495144
TI  - Expansion of IL-6+ Th17-like cells expressing TLRs correlates with microbial
      translocation and neurological disabilities in NMOSD patients.
AB  - Different microbial antigens, by signaling through toll-like receptors (TLR), may
      contribute to Th17-mediated autoimmune diseases, such as neuromyelitis optica
      spectrum disorder (NMOSD). The objective of this study was to determine the
      proportion of different Th17-like cell subsets that express TLR in NMOSD
      patients. For this study, the frequency of different Th17 cell subsets expressing
      TLR subsets in healthy individuals (n=20) and NMOSD patients (n=20) was evaluated
      by cytometry. The peripheral levels of soluble CD14 (sCD14) and cytokines were
      determined by ELISA. Our results demonstrated that the proportion of peripheral
      CD4+ T cells expressing TLR2, 4 and 9 was significantly higher in NMOSD samples
      than in healthy subjects. In NMOSD, these cells are CD28+PD-1-CD57- and produce
      elevated levels of IL-17. Among different TLRs+ Th17-like subsets, the proportion
      of those that co-express IL-17 and IL-6 was significantly higher in NMOSD
      patients, which was positively correlated with sCD14 levels and EDSS score. By
      contrast, the percentage of TLRs+Treg17 cells (IL-10+IL-17+) was negatively
      related to sCD14 and the severity of NMOSD. In conclusion, the expansion of
      peripheral IL-6-producing TLR+ Th17-like cells in NMOSD patients was associated
      with both bacterial translocation and disease severity.

PMID- 28495145
TI  - Medication discrepancy rates among Medicaid recipients at hospital discharge.
AB  - OBJECTIVES: To compare the rate of discrepancies per patient for medications
      changed during hospitalization in patients with and without prescription provider
      comments at hospital discharge. Secondary objectives included comparing 35-day
      readmission rates, describing the overall medication discrepancy rate stratified
      by age group and type of discrepancy, collecting average number of medication
      changes, and reporting percentage change in admission medications at discharge.
      METHODS: This single-center prospective cohort included NC Medicaid recipients
      discharged from East Carolina University Family Medicine service from November 1,
      2015, to January 31, 2016. Patients were assigned to a group based on presence or
      absence of provider comments on discharge prescriptions. Outpatient pharmacy
      claims were compared with the discharge summary to identify medication
      discrepancies. Medication discrepancy rates between groups were to be compared by
      means of independent-samples t test. Medication discrepancy rates were compared
      according to 35-day readmission status, age group, and type of discrepancy by
      means of independent-samples t tests and analysis of variance. Descriptive
      statistics were used for other secondary outcomes. RESULTS: Of 118 patients
      included, only 1 had provider comments. Therefore, a medication discrepancy rate
      comparison was not performed. Patients had a mean of 4 medication changes made to
      their regimen and 21.3% change in admission medications. Sixty-one percent of
      patients had at least 1 medication discrepancy, with an overall rate of 1.19.
      Patients readmitted within 35 days had a significantly greater medication
      discrepancy rate than those not readmitted (1.63 vs. 1.05, respectively; P =
      0.044). Patients 18-49 years of age had the highest discrepancy rate and those
      older than 80 years of age the lowest (1.58 and 0.50, respectively). New or
      changed discharge medication not filled accounted for 69% of discrepancies.
      CONCLUSION: Although medication discrepancies were common, use of provider
      comments was rare. Future studies should address more effective ways to
      communicate pertinent information to community pharmacists and methods to improve
      adherence in obtaining new medications.

PMID- 28495146
TI  - Neonatal Vein of Labbe Infarction Size is Associated With Long-Term Language
      Outcomes.
AB  - BACKGROUND: The vein of Labbe is a superficial cortical vein, which drains the
      lateral surface of the temporal lobe. Thrombosis of the vein of Labbe can occur
      in the neonatal period. The developmental outcomes of infants who had vein of
      Labbe thrombosis are unknown as few studies of outcomes exist. METHODS: We
      completed a retrospective review of infants born >=34 weeks of gestation,
      diagnosed with vein of Labbe thrombosis, and/or infarction on neuroimaging during
      the first 30 days of life. Size of each temporal lobe infarction was estimated
      based on the number of temporal lobe segments involved. Primary outcomes were the
      presence of major neurodevelopmental impairments in childhood and Bayley scores
      at two years. RESULTS: Our cohort of 19 infants had a median gestational age of
      38 weeks (interquartile range 36 to 39) and mean birth weight 2892 +/- 920 grams.
      The most common presenting symptoms of vein of Labbe thrombosis and infarction of
      surrounding tissue were seizures, apnea, lethargy, and either hypertonia or
      hypotonia. At the latest clinical follow-up appointment documented in the
      electronic medical record (mean 4.4 +/- 3.08 years), 44% had major
      neurodevelopmental impairment. Patients with large vein of Labbe infarctions had
      significantly worse average Bayley scores than those with small to moderate
      lesions, and differences in language composite were statistically significant
      (72.7 vs 107.8, P = 0.017). CONCLUSIONS: Neonates with large vein of Labbe
      infarctions are more likely to have poor language outcomes. This finding suggests
      a need for targeted surveillance to ensure early identification of deficits and
      referral for intervention.

PMID- 28495148
TI  - Analysis of urinary PSA glycosylation is not indicative of high-risk prostate
      cancer.
AB  - The levels of core fucosylation and alpha2,3-linked sialic acid in serum Prostate
      Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and
      Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic
      Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the
      present work we evaluated whether these glycosylation determinants could also be
      altered in urinary PSA obtained after digital rectal examination (DRE) and could
      also be useful for diagnosis determinations. For this purpose, alpha2,6-sialic
      acid and alpha1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy
      negative and 35 PCa patients of different aggressiveness degree, were analyzed by
      sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the
      levels of specific glycosylation determinants, that in serum PSA samples were
      indicative of PCa aggressiveness, were not found in PSA from DRE urine samples.
      Although urine is a simpler matrix for analyzing PSA glycosylation compared to
      serum, an immunopurification step was necessary to specifically detect the
      glycans on the PSA molecule. Those specific glycosylation determinants on urinary
      PSA were however not useful to improve PCa diagnosis. This could be probably due
      to the low proportion of PSA from the tumor in urine samples, which precludes the
      identification of aberrantly glycosylated PSA.

PMID- 28495147
TI  - Discrepancies between two immunoassays for the determination of MPO and PR3
      autoantibodies.
AB  - BACKGROUND: Testing for autoantibodies to myeloperoxidase (MPO) and proteinase 3
      (PR3) is part of anti-neutrophil cytoplasmic antibodies (ANCA) test that aids the
      diagnosis of a number of autoimmune diseases including small-vessel vasculitis.
      We characterized the differences between two automated immunoassays at three
      facilities for measuring MPO- and PR3-ANCA autoantibodies. METHODS: 117 serum
      samples were analyzed for MPO and PR3 autoantibodies. The INOVA QUANTA Lite(r)
      IgG assay (INOVA Diagnostics) were performed at two facilities and the Bio
      Plex(r) 2200 Vasculitis Panel (Bio-Rad) were performed at a third reference lab.
      The results were compared both qualitatively (between INOVA QUANTA Lite(r) and
      Bio-Plex(r) methods) and quantitatively (between two sites performing INOVA
      QUANTA Lite(r) assays). RESULTS: Comparison of the INOVA QUNATA Lite(r) assays at
      two different facilities (n=36) demonstrated high concordance (97.2% for MPO and
      94.4% for PR3) and quantitative correlation (R2=0.973 for MPO and R2=0.935 for
      PR3). Conversely, INOVA QUNATA Lite(r) and Bio-Plex(r) methods showed poor
      concordance at 70.4% for MPO (n=81; 95% CI: 59.7% to 79.2%) and at 76.5% for PR3
      (n=81; 95% CI: 66.2% to 84.4%). CONCLUSION: This study demonstrated low
      concordance between two methods for MPO-ANCA and PR3-ANCA measurements. Given the
      discrepancies, the performance of different autoantibody immunoassay methods
      should be taken into consideration when evaluating MPO-ANCA and PR3-ANCA results.

PMID- 28495151
TI  - Research integrity-have we made progress?

PMID- 28495149
TI  - United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for
      Keratoconus Treatment.
AB  - PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking
      (CXL) for the treatment of progressive keratoconus. DESIGN: Prospective,
      randomized, multicenter, controlled clinical trial. PARTICIPANTS: Patients with
      progressive keratoconus (n = 205). METHODS: The treatment group underwent
      standard CXL and the sham control group received riboflavin alone without removal
      of the epithelium. MAIN OUTCOME MEASURES: The primary efficacy criterion was the
      change over 1 year of topography-derived maximum keratometry value, comparing
      treatment with control group. Secondary outcomes evaluated were corrected
      distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA),
      manifest refraction spherical equivalent, endothelial cell count, and adverse
      events. RESULTS: In the CXL treatment group, the maximum keratometry value
      decreased by 1.6 diopters (D) from baseline to 1 year, whereas keratoconus
      continued to progress in the control group. In the treatment group, the maximum
      keratometry value decreased by 2.0 D or more in 28 eyes (31.5%) and increased by
      2.0 D or more in 5 eyes (5.6%). The CDVA improved by an average of 5.7 logarithm
      of the minimum angle of resolution (logMAR) units. Twenty-three eyes (27.7%)
      gained and 5 eyes lost (6.0%) 10 logMAR or more. The UDVA improved 4.4 logMAR.
      Corneal haze was the most frequently reported CXL-related adverse finding. There
      were no significant changes in endothelial cell count 1 year after treatment.
      CONCLUSIONS: Corneal collagen crosslinking was effective in improving the maximum
      keratometry value, CDVA, and UCVA in eyes with progressive keratoconus 1 year
      after treatment, with an excellent safety profile. Corneal collagen crosslinking
      affords the keratoconic patient an important new option to decrease progression
      of this ectatic corneal process.

PMID- 28495152
TI  - An ounce of prevention.

PMID- 28495150
TI  - Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059
      Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture.
AB  - PURPOSE: To determine the personalized rate of uveal melanoma-related metastasis
      on the basis of individual tumor cytogenetic profile. DESIGN: Retrospective case
      series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine
      needle aspiration biopsy (FNAB) for DNA amplification and whole genome array
      based assay were performed for analysis of chromosomes 3, 6, and 8. MAIN OUTCOME
      MEASURES: Melanoma-related metastasis. RESULTS: The mean patient age was 57
      years, and most were white (1026/1059, 97%). The melanoma involved the choroid
      (938/1059, 89%), ciliary body (85/1059, 8%), or iris (36/1059, 3%), with 19%
      being macular in location. The mean largest basal diameter was 11 mm (median, 12
      mm; range, 3-24 mm), and mean thickness was 5 mm (median, 4 mm; range, 1-20 mm).
      On the basis of individual chromosomal mutations, risk for metastasis was
      increased for chromosome 3 partial monosomy (hazard ratio [HR], 2.84; P = 0.001),
      3 complete monosomy (HR, 6.7, P < 0.001), 6q loss (HR, 3.1, P = 0.003), 8p loss
      (HR, 21.5, P < 0.001), and 8q gain (HR, 9.8, P < 0.001). Kaplan-Meier estimate
      for melanoma-related metastasis in 1, 3, 5, and 7 years for 3 partial monosomy
      was 1%, 5%, 14%, and 17%; for 3 complete monosomy was 3%, 19%, 28%, and 37%; for
      6q loss was 8%, 23%, 49%, and 49%; for 8p loss was 8%, 29%, not estimable (NE),
      and NE; and for 8q gain was 6%, 21%, 35%, 48%, respectively. On the basis of
      personalized cytogenetic profiles, Kaplan-Meier estimates (1, 3, and 5 years) for
      melanoma-related metastasis for 3, 6, and 8 disomy (1%, 1%, 4% [HR, 1]) were low
      compared with the higher-risk combinations of 3 complete monosomy, 6p gain, and
      8q gain (0%, 29%, 29% [HR, 10.6, P = 0.02]); 3 complete monosomy, 6 disomy, 8q
      gain, and 8p gain (14%, 14%, NE [HR, 18.3, P = 0.02]); 3 complete monosomy, 6
      disomy, and 8q gain (8%, 27%, 39% [HR, 19.5, P < 0.001]); and 3 complete
      monosomy, 6 disomy, 8q gain, and 8p loss (3%, 28%, NE [HR, 31.6, P < 0.001]),
      respectively. CONCLUSIONS: Risk for melanoma-related metastasis strongly
      correlates with personalized cytogenetic profiles, with 5-year Kaplan-Meier
      estimates ranging from 4% with chromosomes 3, 6, and 8 disomy up to 39% for 3
      complete monosomy, 6 disomy, and 8q gain.

PMID- 28495153
TI  - The next chapter in malaria eradication.

PMID- 28495154
TI  - The prescribing cascade revisited.

PMID- 28495155
TI  - Making sense of polycystic kidney disease.

PMID- 28495156
TI  - Offline: Is the NHS in crisis?

PMID- 28495157
TI  - Concern over India's move to cut funds for PHFI.

PMID- 28495158
TI  - Frontline: Providing care in the midst of the crisis in Yemen.

PMID- 28495159
TI  - Health care in Turkey in the Erdogan era.

PMID- 28495160
TI  - Who is responsible for the health care of refugees?

PMID- 28495161
TI  - Early use of the microscope.

PMID- 28495162
TI  - Mortality decrease according to socioeconomic groups.

PMID- 28495163
TI  - Mortality decrease according to socioeconomic groups.

PMID- 28495164
TI  - Steroid withdrawal and bone disease after kidney transplantation.

PMID- 28495165
TI  - Mortality decrease according to socioeconomic groups - Authors' reply.

PMID- 28495166
TI  - Steroid withdrawal and bone disease after kidney transplantation - Authors'
      reply.

PMID- 28495167
TI  - Bioresorbable vascular scaffolds and late lumen loss.

PMID- 28495168
TI  - Bioresorbable vascular scaffolds and late lumen loss - Authors' reply.

PMID- 28495169
TI  - An error of omission in the report on the clinical trial scene in India.

PMID- 28495170
TI  - Targeted enrichment sequencing in two midterm pregnancies with severe
      abnormalities on ultrasound.

PMID- 28495171
TI  - Tailored genetic testing provides answer to fetal anomaly.

PMID- 28495172
TI  - Cysteine cathepsins B and X promote epithelial-mesenchymal transition of tumor
      cells.
AB  - Cathepsins B and X are lysosomal cysteine carboxypeptidases suggested as having a
      redundant role in cancer. They are involved in a number of processes leading to
      tumor progression but their role in the epithelial-mesenchymal transition (EMT)
      remains unknown. We have investigated the contribution of both cathepsins B and X
      in EMT using tumor cell lines differing in their expression of epithelial and
      mesenchymal markers and cell morphology. Higher levels of both cathepsins are
      shown to promote EMT and are associated with the mesenchymal-like cell phenotype.
      Moreover, simultaneous knockdown of the two peptidases triggers a reverse,
      mesenchymal to epithelial transition. Of the two cathepsins, cathepsin B appears
      to be the stronger promotor of EMT. Furthermore, we evaluated the involvement of
      cathepsin B and X in the transforming growth factor-beta1 (TGF-beta1) signaling
      pathway, one of the key signaling mechanisms triggering EMT in cancer. In MCF-7
      cells the expression of cathepsin B was shown to depend on their activation with
      TGF-beta1 while, for cathepsin X, a TGF-beta1 independent mechanism of induction
      during EMT is indicated. EMT is thus shown to be another mechanism linking
      cathepsins B and X with tumor progression. With silencing of their expression or
      inhibition of enzymatic activity, the tumor cells could be reverted to less
      aggressive epithelial-like phenotype.

PMID- 28495173
TI  - Late treatment of obstetrical brachial plexus palsy by humeral rotational
      osteotomy and lengthening with an intramedullary elongation nail.
AB  - To date, all the authors who have recommended external rotation osteotomy (ERO)
      in the late treatment of obstetrical brachial plexus palsy (OBPP), have neglected
      upper limb length discrepancy, which is an another sequelae of OBPP. In this
      paper, a new technique is reported for the late treatment of OBPP patients with
      upper limb length discrepancy, in which both humeral external rotation osteotomy
      (ERO) and lengthening are applied with an intramedullary elongation nail. With
      this technique, upper limb function is improved through re-orientation of the
      shoulder arc to a more functional range, and further improvements will be seen in
      the appearance of the upper limb with the elimination of length discrepancy. It
      is also advocated that there is a potentiating effect of the humeral lengthening
      on shoulder movements gained by ERO when the osteotomy is applied above the
      deltoid insertion, as this allows more lateralized placement of the deltoid
      insertion.

PMID- 28495174
TI  - PPARgamma-mediated G-protein coupled receptor 120 signaling pathway promotes
      transcriptional activation of miR-143 in adipocytes.
AB  - MicroRNAs (miRNAs), the small noncoding RNAs, regulate various biological
      processes such as adipogenesis. MicroRNA-143 (miR-143) promotes adipocyte
      differentiation, and is correlated with obesity in mice fed a high-fat diet.
      However, the transcriptional regulation of miR-143 is largely unknown. In this
      study, we identified that miR-143 is a target of peroxisome proliferator
      activated receptor gamma (PPARgamma), a key transcription factor in adipogenesis.
      Four putative peroxisome proliferator response elements (PPREs) were identified
      in the miR-143 promoter region. Using chromatin immune-precipitation, we observed
      that PPARgamma was bound with two PPRE regions of the miR-143 promoter in 3T3-L1
      adipocytes. A luciferase reporter assay showed that the PPRE1 region (-1330/
      1309) of the miR-143 promoter played an important role in PPARgamma
      transcriptional activation. In addition, we determined that G-protein coupled
      receptor 120 (GPR 120), which functions as an omega 3 fatty acid receptor,
      affected miR-143 expression in adipocytes. GPR120 silencing in adipocytes
      inhibited the expression of PPARgamma and miR-143, whereas GPR120 overexpression
      led to increased expressions of PPARgamma and miR-143. Silencing of PPARgamma
      inhibited the induction of miR-143 by GPR-120. These results suggested that a
      PPARgamma-mediated GPR120 signaling pathway promotes transcriptional activation
      of miR-143 in adipocytes.

PMID- 28495175
TI  - A case of ureteric polypoid endometriosis presenting in a post-menopausal woman.

PMID- 28495176
TI  - Pubertal Timing and Cardiometabolic Markers at Age 16 Years.
AB  - OBJECTIVE: To examine the association between pubertal timing and cardiometabolic
      markers among adolescents. STUDY DESIGN: We used data from Dutch adolescents
      participating in a birth cohort study. The study population for the current study
      consisted of 799 adolescents of whom data were available for at least 1 of the
      exposure variables (pubertal timing and/or age at menarche) and any of the
      cardiometabolic markers (waist circumference, cholesterol, blood pressure [BP],
      glycated hemoglobin) measured at age 16 years. Adolescents self-reported pubertal
      development at ages 11, 14, and 16 years. We categorized participants with early
      (84 girls, 88 boys), intermediate (240 girls, 211 boys), or late pubertal timing
      (89 girls, 85 boys). We estimated differences in cardiometabolic markers using
      linear regression analysis. RESULTS: Girls with early pubertal timing had 1.54 cm
      larger waist circumference (95% CI .05; 3.03) and 3.98 mm Hg higher systolic BP
      (95% CI 1.69; 6.27) at age 16 years than girls with intermediate pubertal timing.
      The association with systolic BP remained after adjusting for childhood body mass
      index (BMI) (age 8 years) but attenuated after adjusting for BMI in adolescence
      (age 16 years). Boys with early pubertal timing had 0.79 mmol/mol lower glycated
      hemoglobin (95%CI -1.38; -0.20) than boys with intermediate pubertal timing.
      CONCLUSIONS: Girls with early pubertal timing had unfavorable BP levels at age 16
      years, independent of BMI in childhood. Girls and boys with late pubertal timing
      had a tendency for lower waist circumference, but no differences in other
      cardiometabolic markers. Late pubertal timing does not appear to be a risk factor
      for unfavorable cardiometabolic markers in adolescence.

PMID- 28495177
TI  - Three-Month Old with a Tongue Mass.

PMID- 28495178
TI  - Transurethral resection of ejaculatory ducts: a step-by-step guide.
AB  - OBJECTIVE: To demonstrate the key components for completing a successful
      transurethral resection of ejaculatory ducts (TURED) for completely obstructed
      ejaculatory ducts (EDs). DESIGN: Video presentation. SETTING: University
      Hospital. PATIENT(S): A 40-year-old man presenting with primary infertility and
      abnormal semen analysis (pH 6.4, volume of 0.7 cc, concentration 16 million/cc,
      and 7% motility) in whom a transrectal ultrasonography revealed dilated seminal
      vesicles measuring more than 1.5 cm and seminal vesicle aspiration detected no
      sperm in the aspirate. INTERVENTION(S): Transurethral resection of ejaculatory
      ducts. MAIN OUTCOME MEASURE(S): Intraoperative technique with commentary
      highlighting tips for a successful TURED. RESULT(S): This video provides a step
      by-step guide for TURED, including transrectal ultrasonography-guided seminal
      vesicle puncture for instillation of methylene blue to allow more precise
      identification of EDs. Vesiculography was performed near the end of the procedure
      to assess for patency of EDs and confirm both sides had been opened.
      (Institutional review board approval was obtained for this presentation.)
      CONCLUSION(S): The key portions for performing a successful TURED includes
      seminal vesicle instillation of methylene blue for easier identification of EDs.
      Vesiculography is performed near the end of the procedure to ensure both EDs have
      been opened as well as to assess for passive drainage of the seminal vesicles
      through the newly open EDs.

PMID- 28495179
TI  - Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low
      Density Lipoprotein Cholesterol Levels.
AB  - BACKGROUND: Dyslipidemia is a well-known risk factor for carotid stenosis
      progression, but triglycerides have attracted little attention. The aim of this
      study was to assess if serum triglycerides affect progression of carotid stenosis
      in patients with well-controlled low-density lipoprotein cholesterol (LDL-C)
      levels. METHODS: This is a retrospective study in a single hospital consisting of
      71 Japanese patients with internal carotid artery stenosis greater than or equal
      to 50% and normal serum LDL-C levels who underwent angiographic examination with
      or without the resultant carotid artery stenting or endarterectomy from 2007 to
      2011, and were subsequently followed up for 4 years. Clinical factors including
      fasting serum triglyceride values were compared between the progression (>=10%
      increase in degree of carotid stenosis on ultrasonography) and the nonprogression
      groups. RESULTS: During 4 years, 15 patients (21.1%) had carotid stenosis
      progression on either side. Cox regression analysis demonstrated that symptomatic
      cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial
      arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR,
      6.228; P = .011) were associated with subsequent progression of carotid stenosis.
      Kaplan-Meier plots demonstrated that the progression-free survival rate was
      significantly higher in patients without hypertriglyceridemia and intracranial
      arteriosclerotic stenosis at baseline. CONCLUSIONS: Among patients with moderate
      to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an
      important risk factor for progression of carotid stenosis irrespective of
      surgical treatments. It would be worthwhile to test if triglyceride-lowering
      medications suppress carotid stenosis progression.

PMID- 28495180
TI  - Conicity index: An anthropometric measure to be evaluated.

PMID- 28495181
TI  - Assessment of left ventricular function with tissue Doppler echocardiography and
      of B-type natriuretic peptide levels in patients undergoing transcatheter aortic
      valve implantation.
AB  - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an emerging
      minimally invasive treatment modality in high surgical risk or inoperable
      patients. AIM: The aim of this study was to ascertain the effect of TAVI on left
      ventricular (LV) systolic and diastolic function and serum B-type natriuretic
      peptide (BNP) levels in high surgical risk or inoperable patients with severe
      aortic stenosis. METHODS: Fifty-five patients were included in our retrospective
      study. LV systolic and diastolic function was assessed with conventional and
      tissue Doppler imaging (TDI) prior to and after TAVI. Additionally, BNP was
      measured 24 h before and three months after the procedure. Echocardiographic
      controls were performed at one, three and six months and one year and mean values
      were taken. At the end of the study, LV systolic and diastolic function, serum
      BNP levels and New York Heart Association functional capacity were assessed and
      compared to baseline parameters. RESULTS: The TAVI procedure was successful in
      all patients. In-hospital mortality was 1.8% (one patient). There was a
      substantial improvement in LV function and functional capacity at follow-up. In
      addition, a statistically significant decrease was detected in serum BNP levels
      post-TAVI (median 380 pg/ml [176.6-929.3] vs. 215 pg/ml [96.0-383.0], p=0.0001).
      Only one patient required a permanent pacemaker (1.8%) and there was no mortality
      after TAVI during follow-up. There were significant increases in LV ejection
      fraction and aortic valve area (51.0+/-13.1% vs. 58.4+/-9.1%, p<0.001, and 0.6+/
      0.1 cm2 vs. 2.1+/-0.2 cm2, p=0.0001, respectively). At the end of the study,
      conventional Doppler echocardiography revealed improvement in diastolic function,
      with an increase in mitral E wave, a decrease in mitral A wave and an increase in
      E/A ratio. Deceleration time and isovolumetric relaxation time were shortened and
      myocardial performance (Tei) index decreased. TDI showed an increase in systolic
      myocardial velocity (Sm) and early diastolic velocity (Em). Septal mitral annular
      Sm and Em were increased, whereas MPI was reduced. CONCLUSION: We found that LV
      structural changes and diastolic dysfunction occur in patients with severe aortic
      stenosis and that TAVI is able to reverse these abnormalities, which we
      demonstrated by both conventional echocardiography and TDI. In addition, serum
      BNP levels were decreased after TAVI.

PMID- 28495182
TI  - Threats to internal validity in renal sympathetic denervation trials.

PMID- 28495183
TI  - IDF Clinical Practice Recommendation on the Diabetic Foot: A guide for healthcare
      professionals.

PMID- 28495184
TI  - Interleukin-1beta as emerging therapeutic target in hematological malignancies
      and potentially in their complications.
AB  - Interleukin-1beta (IL-1beta) is a pleiotropic cytokine that exerts multiple roles
      in both physiological and pathological conditions. It is produced by different
      cell subsets, and drives a wide range of inflammatory responses in numerous
      target cells. Enhanced IL-1beta signaling is a common event in patients of
      hematological malignancies. Recent body of evidence obtained in preclinical
      models shows the pathogenic role of these alterations, and the promising
      therapeutic value of IL-1 targeting. In this review, we further highlight a
      potential contribution of IL-1beta linking to complications and autoimmune
      disease that should be investigated in future studies. Hence, drugs that target
      IL-1 may be helpful to improve outcome or reduce morbidity in patients. Some of
      them are FDA-approved, and used efficiently against autoimmune diseases, like IL
      1 receptor antagonist. In the clinic, however, this agent seems to have limited
      properties. Current improved drugs will allow to determine the true potential of
      IL-1 and IL-1beta targeting as therapy in hematological malignancies and their
      related complications.

PMID- 28495185
TI  - Association of circulatory asymmetric dimethylarginine (ADMA) with diabetic
      nephropathy in Asian Indians and its causative role in renal cell injury.
AB  - AIM: Asymmetric dimethylarginine (ADMA) is involved in the regulation of nitric
      oxide synthesis and in the maintenance of vascular tone and structure. But the
      role and status of ADMA in diabetes induced kidney injury is not clear. Hence
      this study is investigating the role of ADMA in the progression of kidney injury
      and its circulatory status in Asian Indians with and without diabetic
      nephropathy. METHODS: Recruited study subjects were divided into normal glucose
      tolerance (NGT), type 2 diabetes mellitus (T2DM) and T2DM with micro or
      macroalbuminuria. Albuminuria was calculated using urinary albumin and creatinine
      ratio (UACR). ADMA was measured using ELISA. Kidney cell damage in terms of
      fibrotic markers and ADMA metabolism in terms of DDAH activity were investigated
      in kidney fibroblasts and mesangial cells. RESULTS: There was a significant
      elevation in plasma ADMA levels in micro and macroalbuminuric diabetic patients.
      We found a significant positive correlation between ADMA and UACR, serum
      creatinine, HbA1C and fasting plasma glucose. A cut-off value of ADMA, 0.666MUM/l
      had a sensitivity and specificity of 70.0% and 65.6%, respectively for detecting
      diabetic nephropathy. DDAH activity was significantly decreased and fibrotic
      markers such as fibronectin and alpha-SMA were significantly increased upon high
      glucose and ADMA treatment. CONCLUSION: We are suggesting a causative role of
      ADMA in the development of kidney injury in terms of renal fibrosis and also a
      cut point of 0.666MUM/l of plasma ADMA level appears to be a predictive risk
      threshold for diabetic nephropathy in south Asian Indian population.

PMID- 28495186
TI  - Puerperal uterine inversion from two viewpoints: Its recurrence at the next
      pregnancy and "unavoidable"-procedure-associated inversion.

PMID- 28495187
TI  - Comment on "Potentized estrogen in homeopathic treatment of endometriosis
      associated pelvic pain: A 24-week, randomized, double-blind, placebo-controlled
      study".

PMID- 28495188
TI  - Comparison of two environmental sampling tools for the detection of Clostridium
      difficile spores on hard bathroom surfaces in the hospital setting.

PMID- 28495189
TI  - Genetic analysis of Rhipicephalus sanguineus sensu lato ticks parasites of dogs
      in Africa north of the Sahara based on mitochondrial DNA sequences.
AB  - The aim of this work was to determine the evolutionary relationship among tick
      populations of Rhipicephalus sanguineus sensu lato distributed in Africa north of
      the Sahara and different lineages of R. sanguineus s.l. distributed in different
      regions of Sub-Saharan Africa, America and Europe through the analysis of DNA
      sequences of two mitochondrial genes. One hundred and thirty six 16S rRNA gene
      sequences and twenty-seven 12S rRNA gene sequences of R. sanguineus s.l. were
      analyzed. Phylogenetic analyses were performed including different lineages of R.
      sanguineus s.l. from America, Europe and Africa, and species belonging to the R.
      sanguineus group as Rhipicephalus camicasi, Rhipicephalus guilhoni, Rhipicephalus
      sulcatus, Rhipicephalus rossicus, Rhipicephalus pusillus, Rhipicephalus turanicus
      and Rhipicephalus leporis. At least two different lineages of R. sanguineus s.l.
      are living in sympatry in Africa north of the Sahara. One of these mitochondrial
      lineages belongs to the same evolutionary entity that R. sanguineus s.l. from
      tropical areas of America, R. sanguineus s.l. from Sub-Saharan Africa, R.
      camicasi and R. guilhoni. The other mitochondrial lineage of R. sanguineus s.l.
      present in Africa north of the Sahara is phylogenetically associated to R.
      sanguineus s.l. ticks from southeastern Europe (Romania, Turkey and Greece). Both
      evolutionary entities are clearly different to the evolutionary entity formed by
      R. sanguineus s.l. from western Europe and temperate areas of America. Thus, the
      name R. sanguineus s.s. cannot be assigned to any of the two evolutionary
      entities present in Africa north of the Sahara. The taxonomic status of these
      taxa will remain unresolved until new lines of evidence become available to
      complement the current results based on mitochondrial DNA.

PMID- 28495190
TI  - Antibodies to Toxoplasma gondii and Leishmania spp. in domestic cats from Luanda,
      Angola.
AB  - Toxoplasma gondii and Leishmania spp. are zoonotic protozoa of importance to
      animal and public health. The present study aimed to assess for the first time
      the seroprevalence of these zoonotic parasites in a domestic feline population
      living in Luanda, Angola. One hundred and two cats were sampled at a veterinary
      medical centre, from May 2014 to February 2016. The age of the cats ranged from
      2.5 to 143 months (median: 12 months; interquartile range: 7.5-24). Serum samples
      were tested for immunoglobulin (Ig) G antibodies to T. gondii at two-fold
      dilutions of 1:20 to 1:2560 with a modified agglutination test (MAT) commercial
      kit. The direct agglutination test (DAT) for titration of IgG antibodies specific
      to Leishmania spp. used a standard freeze-dried antigen at a concentration of
      5*107 promastigotes per milliliter, following a predefined protocol. Two-fold
      dilution series ranging from 1:25 to 1:800 were tested, with a cut-off titre of
      100 chosen for seropositivity. Four out of 102 cats (3.9%; 95% confidence
      interval [CI]: 1.1-9.7) had antibodies to T. gondii: one had a titer of 20, one a
      titer of 160, and two had a titer>=2560. No cat (0.0%; CI: 0.0-3.5) was found
      seropositive for Leishmania spp. A statistically significant difference was found
      between T. gondii seroprevalence and Leishmania spp. seroprevalence (p=0.043).
      The odds of a cat being seropositive to T. gondii increased by an average factor
      of 1.58 for each 1-year increase in age (p=0.003). The sampled cats were well
      cared animals and may not represent the overall feline population of Angola at
      the national and city levels. The fact that only 12 out of the 102 sampled cats
      ate or had access to raw or undercooked meat and/or viscera may have reduced the
      likelihood of finding seropositive results. Under these circumstances, additional
      studies, including a larger number of cats, are necessary for a more
      comprehensive assessment of the zoonotic risk posed by these animals in Angola.

PMID- 28495191
TI  - Review on the immunological and molecular diagnosis of neosporosis (years 2011
      2016).
AB  - Neosporosis, caused by the apicomplexan protozoan Neospora caninum, is a disease
      which affects a wide range of mammalian hosts (mainly cattle and dogs). N.
      caninum infection is considered the major cause of livestock abortions worldwide,
      and therefore is responsible for great losses in the industry. Because there are
      no effective treatments or vaccines, diagnosis is essential for pathogen control.
      Studies of N. caninum mechanisms of pathogenesis have led to the identification
      of new antigens, including NcSRS2, NcSAG1, Ncp40, NcSUB1, NcMIC10, and NcGRAs;
      and a variety of molecular and immunological assays, based on these molecules,
      have been proposed to detect N. caninum in tissues or serum samples. We report
      advances achieved in the last five years in neosporosis control, based on the
      immunological and molecular diagnostic tests.

PMID- 28495192
TI  - Effect of creep-fed supplement on the susceptibility of pasture-grazed suckling
      lambs to gastrointestinal helminths.
AB  - This study evaluated the effect of creep feeding a protein supplement on the
      susceptibility of suckling lambs to infection with gastrointestinal helminths.
      Male and female lambs were grazed on Brachiaria spp. pastures next to their
      mothers. Animals were allocated to one of two treatments: creep feeding (261g/d)
      and control (no supplementation). The trial period was the suckling of lambs
      during two years of study: May-October 2013 and March-July 2014. Supplementary
      creep feeding of lambs improved animal performance (P<0.05). Creep-fed lambs
      reached 18kg body weight in 64 d, but unsupplemented lambs required 77 d to reach
      the same weight. Lambs were susceptible to helminth infection during lactation;
      lambs in both treatments had high fecal egg counts (FECs), with means >1000 eggs
      per gram, as early as 45days of age, when the daily grazing time per animal
      increased. Creep feeding reduced the FECs of suckling lambs >60days of age in
      infections dominated by Haemonchus contortus. Totals of 20 and 48 anthelmintic
      treatments were administered to the supplemented and unsupplemented animals,
      respectively. The effect of this variable, however, was significant (P<0.05) only
      after 60days, when nine and 28 treatments had been administered to the
      supplemented and unsupplemented lambs, respectively. The number of strongyloid
      larvae recovered from the paddock did not differ significantly (P >0.05) between
      the two treatments, indicating similar challenges by infective larvae to both
      groups. The supplementation of lambs by creep feeding can thus be a strategy for
      the sustainable control of helminth infection, because it reduces the dependence
      on anthelmintic treatment.

PMID- 28495193
TI  - First genetic characterization of Toxoplasma gondii in stray cats from Algeria.
AB  - Toxoplasmosis is a parasitic disease with worldwide distribution and a major
      public health problem. In Algeria, no data are currently available about
      genotypes of Toxoplasma gondii isolated from animals or humans. The present study
      assesses for the first time the seroprevalence of toxoplasmosis in stray cats,
      and provides molecular characterization of T. gondii strains circulating in this
      feline population in Algiers, the capital city of Algeria. Sera from 96 stray
      cats were tested for the presence of antibodies against T. gondii using the
      modified agglutination test. The seroprevalence was 50% (48/96) using 1:6 as the
      positivity cut-off. Different organs samples from stray cats, including heart
      samples, were tested for the presence of Toxoplasma DNA using real-time PCR. T.
      Gondii DNA was detected in 90.6% (87/96) of hearts. Of these parasitic DNAs, 22
      were submitted to genotyping through the analysis of 15 microsatellite markers.
      The identified genotypes (12 of 22) mainly belonged to the type II lineage.

PMID- 28495194
TI  - Neospora caninum abortion in a Malayan tapir (Tapirus indicus).
AB  - A captive 17-year old female Malayan tapir (Tapirus indicus) aborted a fetus with
      a crown rump length of 19cm in early pregnancy. The fetus showed an early state
      of mummification. Histologically, a multifocal mononuclear encephalitis,
      myocarditis and periportal hepatitis was present indicating a possible protozoal
      cause of abortion. Although immunohistologically, Neospora (N.) caninum antigen
      could not be demonstrated, N. caninum DNA was detected by Polymerase Chain
      Reaction (PCR) in brain, heart, liver and lung of the fetus. N. caninum DNA was
      extracted from the aborted fetus and the microsatellite marker MS10 was amplified
      by PCR and sequenced. The obtained MS10 microsatellite pattern has not been
      described in Germany yet. Nevertheless, the MS10 pattern was very similar to
      those reported for N. caninum isolated from dogs and cattle in Germany. Because
      of the histological pattern and extent of the lesions, neosporosis was suspected
      as the cause of fetal death and abortion. This case report describes for the
      first time transplacental transmission of N. caninum and abortion due to
      neosporosis in a tapir.

PMID- 28495195
TI  - In vitro repellency of DEET and beta-citronellol against the ticks Rhipicephalus
      sanguineus sensu lato and Amblyomma sculptum.
AB  - Rhipicephalus sanguineus sensu lato and Amblyomma sculptum can parasite humans
      and domestic animals and are vectors of pathogens, including zoonoses. Repellents
      are an important tool of tick control. This study aimed to compare the efficacy
      of N,N-diethyl- 3-methylbenzamide (DEET), a standard repellent, versus beta
      citronellol in a Petri dish bioassay. A semicircle of filter paper (31.8cm2) was
      treated with 87MUl of one of four concentrations (0.200, 0.100, 0.050 and
      0.025mg/cm2) of beta-citronellol, DEET or solvent (ethanol). A head-to-head test
      was developed treating one side with increasing concentrations of beta
      citronellol as above mentioned, against the highest concentration of DEET.
      Besides that a blank assay was performed. Three males and three females were
      placed in the middle of the plate and their location was evaluated 5, 10 and
      30min after the test was initiated. As a result, the time had no significant
      effect on repellency response of the ticks exposed to both compounds and their
      concentrations. The repellency response raised according with the increase of
      concentration. Additionally, our findings indicate that the tick A. sculptum was
      more sensitive to the compounds tested and beta-citronellol showed a higher
      efficacy than DEET. In addition, beta-citronellol could be formulated to protect
      humans and other animals from R. sanguineus s. l. and A. sculptum infestation, as
      well as the diseases transmitted by these species.

PMID- 28495196
TI  - Pharmacokinetics of a novel spot-on formulation of praziquantel for dogs.
AB  - Praziquantel (PZQ) is an anthelmintic drug used both in humans and animals that
      can be administered through various routes. There are transdermal formulations
      for cats, but only oral or subcutaneous dosage forms for dogs. Given the fact
      that the cat's skin and the dog's skin have different characteristics, which in
      turn affect bioavailability, we developed a PZQ spot-on formulation for dogs.
      This study was aimed at determining the plasmatic behavior of topically
      administered PZQ (Labyes(r)) in adult dogs. Dogs were administered PZQ (14.5mg/kg
      PZQ, from a solution of 100mg/ml). Blood samples were drawn before treatment
      onset and at the following time points after PZQ administration: 1, 2, 4, 6, 12,
      24 and 48h. PZQ plasma concentration was determined by ultra-high performance
      liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS/MS).
      Observed maximum concentration (Cmax), area under the concentration-time curve
      from the time of drug administration to infinity (AUCinf) and time to maximum
      concentration (Tmax) were calculated for each animal, and mean+/-SD for each
      parameter was obtained. Results were as follows: Cmax=56.0+/-15ng/ml;
      AUCinf=910.2+/-220ng*h/ml, Tmax=5.0+/-1.1h. This is the first study to provide
      pharmacokinetic data of a praziquantel spot-on formulation for dogs.

PMID- 28495197
TI  - Randomized, allopurinol-controlled trial of the effects of dietary nucleotides
      and active hexose correlated compound in the treatment of canine leishmaniosis.
AB  - First-line treatment for canine leishmaniosis (CanL) is N-methylglucamine
      antimoniate (MGA) combined with allopurinol. However, in some dogs allopurinol
      may induce hyperxanthinuria leading to urolithiasis. Moreover, allopurinol
      resistance has recently been described in Leishmania infantum isolates from
      treated dogs with a relapse of the disease. Alternative treatments are thus
      needed. Since the type of host immune response strongly influences CanL
      progression and prognosis, dogs could benefit from treatments targeted at
      modulating such response, such as nucleotides and active hexose correlated
      compound (AHCC). The aim of this study was to evaluate the effects of an oral
      combination of nucleotides and AHCC in dogs with clinical leishmaniosis. Sixty
      nine dogs with naturally-occurring clinical leishmaniosis were included in this
      multicenter, open-label, positively-controlled clinical trial and randomized to
      receive 10mg/kg allopurinol PO BID (allopurinol group) or 17mg/kg AHCC plus
      32mg/kg nucleotides PO SID (supplement group) for 180 days. All dogs were also
      given 50mg/kg MGA SC BID during the first 28 days. At the time points 0, 30, and
      180 days of the trial, dogs underwent a clinical examination, and blood, urine,
      and bone marrow samples were submitted for analytical tests. Final data analyses
      (allopurinol group: n=29; supplement group: n=24) revealed a significant
      improvement in both groups in clinical scores and ELISA-determined antibody
      titers after treatment. However, the supplement group showed a significantly
      lower clinical score (P=0.005) and significantly higher antibody titers (P=0.032)
      after 180 days, compared to the allopurinol group. RT-PCR parasite loads were
      reduced in groups (mean+/-SD supplement: 0.38+/-0.56 vs 5.23+/-18.9; allopurinol:
      0.45+/-1.47 vs 3.09+/-8.36 parasites/ng of DNA), but there were no significant
      differences over time or between groups. During the study, 12 dogs in the
      allopurinol group developed xanthinuria (41%) compared to no dogs (0%) in the
      supplement group (P=0.000). Both treatments led to significantly increased
      CD4+/CD8+ ratio, and improvements in protein electrophoretic pattern and acute
      phase response. In conclusion, 6-month oral treatment with nucleotides and AHCC
      in addition to MGA showed similar efficacy to the current first-line treatment
      for CanL, without producing xanthinuria. This combination could be a good
      alternative to MGA-allopurinol combination treatment for CanL, especially for
      dogs suffering allopurinol-related adverse events.

PMID- 28495198
TI  - Phenotypic expression of parasite susceptibility to Haemonchus contortus in
      Pelibuey sheep.
AB  - The objective of this study was to determine if the mean faecal egg count (FEC)
      from a first experimental Haemonchus contortus infection could be used to
      classify parasite-naive Pelibuey hair sheep as parasite-resistant high responders
      and parasite-susceptible low responders. Twenty 6- to 7-month-old Pelibuey male
      sheep raised free of gastrointestinal nematodes were challenged with 7500+/-1412
      H. contortus L3 larvae administrated orally on day 0 of the study. Faecal samples
      from each lamb were obtained daily from 21 to 41days post-infection (Stage I).
      Lambs received a second artificial infection of 8420+/-1545L3 larvae on day 42,
      with faecal samples collected from day 65 to day 78 (Stage III). The mean FEC for
      each lamb in Stage I was used to classify 8 lambs with means for FEC that were
      more than two standard errors (SE) below the overall mean (i.e., <4764 eggs per
      gram of feces; epg) as high responders. The remaining 12 lambs were classified as
      low responders. Means for FEC in Stage I were 2449+/-194 epg for high responders
      and 14,461+/-1044 epg for low responders (P<0.05). High responders also had lower
      FEC than low responders in Stage III (actual means of 650+/-220 vs. 5933+/-1990
      epg; P<0.05 following log transformation to normalize the FEC distribution).
      Lambs were then reclassified as high and low responders based on their mean FEC
      in Stage III. Fourteen lambs with means for FEC that were more than one standard
      error (SE) below the overall mean (i.e., below 1537 epg) were classified as high
      responders. The remaining six lambs were classified as low responders. Use of the
      Stage I responder class to predict the Stage III responder class resulted in an
      83.3% sensitivity but only a 50% specificity. The positive predictive value was
      41.7% and the negative predictive value was 87.5%. The poor positive predictive
      value was caused by 5 animals with high FEC in Stage I, but low FEC in Stage III.
      The first infection thus identified most high-responder lambs, but a second
      infection may improve accuracy by separating lambs with an intermediate level of
      resistance from truly susceptible lambs. This protocol now requires additional
      validation under more practical conditions involving natural parasite infections
      and larger lamb numbers.

PMID- 28495199
TI  - An automated, multiplex-tandem PCR platform for the diagnosis of gastrointestinal
      nematode infections in cattle: An Australian-European validation study.
AB  - Detecting the genera and species of gastrointestinal (GI) nematode infections in
      faecal samples obtained from cattle requires the incubation of faeces ('larval
      culture') followed by identification of the third-stage larvae that are harvested
      after 10-14days. Substantial research in the development of PCR-based methods for
      the rapid and specific identification GI nematodes has been conducted for small
      ruminants, whilst only few such assays have been developed for cattle. In the
      present paper we describe the development of an automated, robotic PCR platform
      for the detection and genus and/or species-specific identification of GI
      nematodes from bovine faecal samples. This test was then validated using samples
      from different regions of three countries (Australia, Belgium and Scotland). The
      PCR platform was found to be highly sensitive and specific for the identification
      of the important GI nematodes in naturally infected cattle (both estimates >90%).
      The PCR platform can also estimate the percentage of genera or species present in
      a mixed-species infection, and was found superior to larval culture in terms of
      speed (1-2days versus 1-2 weeks for culture), sensitivity and specificity. The
      PCR was simple to use and the operator requires no knowledge or experience to
      identify the nematodes present, compared to larval culture where even experienced
      operators can make substantial errors due to considerable overlap in the
      published characteristics of key species.

PMID- 28495200
TI  - Genotyping of Theileria lestoquardi from sheep and goats in Sudan to support
      control of Malignant Ovine Theileriosis.
AB  - Theileriosis, caused by parasitic protozoa of the genus Theileria parasites, are
      among the major tick-borne diseases of ruminant livestock. The largest economic
      losses are attributed in particular to those caused by the leukoproliferative
      species of Theileria: T. parva, T. annulata and T. lestoquardi. Theileria
      lestoquardi is transmitted by Hyalomma ticks and causes malignant ovine
      theileriosis (MOT), a disease that is particularly prevalent in Sudan. The
      disease is considered of a high economic importance in Sudan, where export of
      sheep is a major component of the national economy. A live vaccine based on a
      Sudanese isolate of T. lestoquardi (Atbara strain) was previously developed for
      the control of MOT in Sudan, but not yet deployed in the field. The present study
      aims to genetically characterize and compare samples of T. lestoquardi
      circulating in Sudan as well as the live vaccine isolate in order to understand
      vaccine breakthroughs and failure that may occur. Sheep and goats blood samples
      were collected from six regions in Sudan that are known to be endemic for T.
      lestoquardi infection or have experienced outbreaks of MOT. Blood samples
      infected with T. lestoquardi were identified by PCR or RLB. Genotyping was
      carried out by (1) sequencing the homologues of two T. parva CD8+ T cell antigen
      genes, Tp1 and Tp2, and (2) using a panel of seven micro- and mini-satellite
      markers. A total of 100 T. lestoquardi positive field samples and the T.
      lestoquardi (Atbara) vaccine were genotyped. The results showed that all samples
      had mixed genotypes, with several alleles identified at one or more loci. The
      gene diversity ranged from 0.7840 (TS8) to 0.2133 (TS12) with mean values of
      0.5470. PCA revealed three clusters of the parasite in Sudan; interestingly one
      independent cluster was clearly seen, corresponding to the vaccine isolate. The
      T. lestoquardi Tp1 homologue showed higher homology with T. annulata than with T.
      parva sequences included the defined single CD8+ T cell target epitope region.
      The result indicates that multiple genotypes are a common feature of T.
      lestoquardi infection in Sudan. Both genotyping and the sequencing results
      clearly showed that the vaccine isolate is highly distinct from the field
      samples. This finding raised the question whether vaccination with the prepared
      lived vaccine will effectively protect animals against challenges by the field
      isolates of T. lestoquardi. The results of this work will inform on the best
      approach for controlling MOT in Sudan.

PMID- 28495201
TI  - Self-reported balance status is not a reliable indicator of balance performance
      in adolescents at one-month post-concussion.
AB  - OBJECTIVES: To determine if self-reported balance symptoms can be used as a proxy
      for measures of the center of pressure (COP) to identify balance deficits in a
      group of concussed adolescents. DESIGN: Case-control. METHODS: Thirteen
      adolescents 1-month post-concussion who reported ongoing balance problems
      (Balance+), 20 adolescent 1-month post-concussion who reported no balance
      problems (Balance-), and 30 non-injured adolescents (control) completed a series
      of balance tests. Participants completed two 2-min trials standing on a Nintendo
      Wii Balance BoardTM during which the COP under their feet was recorded: i) double
      leg stance, eyes open; ii) double-leg stance, eyes closed. Participants also
      completed a dual-task condition combining a double-leg stance and a Stroop Colour
      word test. RESULTS: Participants in both the Balance+ and Balance- group swayed
      over a larger ellipse area compared to the control group while completing the
      Eyes Closed (Balance+, p=0.002; Balance-, p=0.002) and Dual-Task (Balance+,
      p=0.001; Balance-, p=0.004) conditions and performed the Dual-Task condition with
      faster medio-lateral velocity (Balance+, p=0.003; Balance-, p=0.009). The
      participants in the Balance- group also swayed over a larger ellipse area
      compared to the control group while completing the Eyes Open condition (p=0.005).
      No significant differences were identified between the Balance+ and Balance-
      groups. CONCLUSIONS: At 1-month post-concussion, adolescents demonstrated balance
      deficits compared to non-injured adolescents regardless of whether they reported
      balance problems. These results suggest that self-reported balance status might
      not be an accurate reflection of balance performance following a concussion in
      adolescents.

PMID- 28495202
TI  - Editor's Perspectives - May 2017.

PMID- 28495203
TI  - Treatment of air leak in polytrauma patients with blunt chest injury.
AB  - INTRODUCTION: Precise diagnostics and an adequate therapeutic approach are
      mandatory in the treatment of air leak in polytrauma patients with blunt chest
      trauma. The aim of this study was to evaluate the incidence, characteristics, and
      management of air leak following this injury pattern. PATIENTS AND METHODS: Data
      from 110 polytrauma patients was collected retrospectively. Fifty-four patients
      received initial treatment by chest tube placement for pneumothorax. These
      patients were classified into two groups, one with severe air leak and one with
      minor air leak. An evaluation of injury pattern, chest wall injuries in
      particular, duration of air leak, reason for drainage maintenance in place,
      hospital length of stay, ICU stay, ventilator duration, type of treatment, and
      the delay to surgical intervention was performed. RESULTS: Whereas 4 patients
      showed severe air leak and were subsequently scheduled for timely surgical
      intervention, the remaining 50 patients only showed minor air leak. Only 7
      patients with minor air leak suffered from prolonged air leak (>5days), which
      spontaneously resolved in all of them after a mean duration of 7.7days (range 6
      12days). Absence of a prolonged air leak resulted in a shorter length of stay and
      a shorter duration of mechanical ventilation, although no statistical
      significance was observed. CONCLUSIONS: Early spontaneous cessation of most minor
      air leaks as well as early surgical intervention for severe air leak lead to very
      satisfactory patient outcomes with a relatively short hospital stay in our
      patients. We therefore advocate early surgery for lacerations of the pulmonary
      parenchyma resulting in severe air leak, whereas minor air leaks can usually be
      treated conservatively.

PMID- 28495204
TI  - Intracranial pressure monitoring in severe traumatic brain injuries: a closer
      look at level 1 trauma centers in the United States.
AB  - INTRODUCTION: The Brain Trauma Foundation (BTF) recently updated recommendations
      for intracranial pressure (ICP) monitoring in severe traumatic brain injury
      (TBI). The effect of ICP monitoring on outcomes is controversial, and compliance
      with BTF guidelines is variable. The purpose of this study was to assess both
      compliance and outcomes at level I trauma centers. MATERIALS AND METHODS: The
      American College of Surgeons Trauma Quality Improvement Program database was
      queried for all patients admitted to level I trauma centers with isolated blunt
      severe TBI (AIS>3, GCS<9) who met criteria for ICP monitoring. Patients who had
      severe extracranial injuries, craniectomy, or death in the first 24h were
      excluded. Comparison between groups with and without ICP monitoring was made,
      analyzing demographics, comorbidities, mechanism of injury, head Abbreviated
      Injury Scale (AIS), vital signs on admission, head CT scan findings. Outcomes
      included in-hospital mortality, mechanical ventilation days, intensive care unit
      (ICU) length of stay, hospital length of stay, systemic complications, and
      functional independence at discharge. Multivariable analysis was used to identify
      independent risk factors for each of the outcomes. RESULTS: Overall, 4880
      patients were included. ICP monitoring was used in 529 patients (10.8%). Stepwise
      logistic regression analysis identified ICP monitor placement as an independent
      risk factor for mortality (OR 1.63; 95% CI 1.28-2.07; p<0.001), mechanical
      ventilation (OR 5.74 95% CI 4.42-7.46; p<0.001), ICU length of stay (OR 4.03; 95%
      CI 2.94-5.52; p<0.001), systemic complications (OR 2.78; 95% CI 2.29-3.37;
      p<0.001), and decreased functional independence at discharge (OR 1.71 95% CI 1.29
      2.26; p<0.001). Subgroup analysis of patients with head AIS 3, 4, and 5 confirmed
      that ICP monitors remained an independent risk factor for mortality in both head
      AIS 4 and 5. CONCLUSIONS: Compliance with BTF guidelines for ICP monitoring is
      low, even at level I trauma centers. In this study, ICP monitoring was associated
      with poor outcomes, and was found to be an independent risk factor for mortality.
      Further studies are needed to determine the optimal role of ICP monitoring in the
      management of severe TBI.

PMID- 28495205
TI  - Gatekeeping and the utilization of physician services in France: Evidence on the
      Medecin traitant reform.
AB  - In 2005, France implemented a gatekeeping reform designed to improve care
      coordination and to reduce utilization of specialists' services. Under this
      policy, patients designate a medecin traitant, typically a general practitioner,
      who will be their first point of contact during an episode of care and who will
      provide referrals to specialists. A key element of the policy is that patients
      who self-refer to a specialist face higher cost sharing than if they received a
      referral from their medecin traitant. We consider the effect of this policy on
      the utilization of physician services. Our analysis of administrative claims data
      spanning the years 2000-2008 indicates that visits to specialists, which were
      increasing in the years prior to the implementation of the reform, fell after the
      policy was in place. Additional evidence from the administrative claims as well
      as survey data suggest that this decline arose from a reduction in self
      referrals, which is consistent with the objectives of the policy. Visits fell
      significantly both for specialties targeted by the policy and specialties for
      which self-referrals are still allowed for certain treatments. This apparent
      spillover effect may suggest that, at least initially, patients did not
      understand the subtleties of the policy.

PMID- 28495206
TI  - Universal block diagram based modeling and simulation schemes for fractional
      order control systems.
AB  - Universal block diagram based schemes are proposed for modeling and simulating
      the fractional-order control systems in this paper. A fractional operator block
      in Simulink is designed to evaluate the fractional-order derivative and integral.
      Based on the block, the fractional-order control systems with zero initial
      conditions can be modeled conveniently. For modeling the system with nonzero
      initial conditions, the auxiliary signal is constructed in the compensation
      scheme. Since the compensation scheme is very complicated, therefore the
      integrator chain scheme is further proposed to simplify the modeling procedures.
      The accuracy and effectiveness of the schemes are assessed in the examples, the
      computation results testify the block diagram scheme is efficient for all Caputo
      fractional-order ordinary differential equations (FODEs) of any complexity,
      including the implicit Caputo FODEs.

PMID- 28495207
TI  - Targeting the Hsp90 C-terminal domain to induce allosteric inhibition and
      selective client downregulation.
AB  - BACKGROUND: Inhibition of Hsp90 is desirable due to potential downregulation of
      oncogenic clients. Early generation inhibitors bind to the N-terminal domain
      (NTD) but C-terminal domain (CTD) inhibitors are a promising class because they
      do not induce a heat shock response. Here we present a new structural class of
      CTD binding molecules with a unique allosteric inhibition mechanism. METHODS: A
      hit molecule, NSC145366, and structurally similar probes were assessed for
      inhibition of Hsp90 activities. A ligand-binding model was proposed indicating a
      novel Hsp90 CTD binding site. Client protein downregulation was also determined.
      RESULTS: NSC145366 interacts with the Hsp90 CTD and has anti-proliferative
      activity in tumor cell lines (GI50=0.2-1.9MUM). NSC145366 increases Hsp90
      oligomerization resulting in allosteric inhibition of NTD ATPase activity
      (IC50=119MUM) but does not compete with NTD or CTD-ATP binding. Treatment of
      LNCaP prostate tumor cells resulted in selective client protein downregulation
      including AR and BRCA1 but without a heat shock response. Analogs had similar
      potencies in ATPase and chaperone activity assays and variable effects on
      oligomerization. In silico modeling predicted a binding site at the CTD dimer
      interface distinct from the nucleotide-binding site. CONCLUSIONS: A set of
      symmetrical scaffold molecules with bisphenol A cores induced allosteric
      inhibition of Hsp90. Experimental evidence and molecular modeling suggest that
      the binding site is independent of the CTD-ATP site and consistent with unique
      induction of allosteric effects. GENERAL SIGNIFICANCE: Allosteric inhibition of
      Hsp90 via a mechanism used by the NSC145366-based probes is a promising avenue
      for selective oncogenic client downregulation.

PMID- 28495209
TI  - Young children consider individual authority and collective agreement when
      deciding who can change rules.
AB  - Young children demonstrate awareness of normativity in various domains of social
      learning. It is unclear, however, whether children recognize that rules can be
      changed in certain contexts and by certain people or groups. Across three
      studies, we provided empirical evidence that children consider individual
      authority and collective agreement when reasoning about who can change rules. In
      Study 1, children aged 4-7years watched videos of children playing simply sorting
      and stacking games in groups or alone. Across conditions, the group game was
      initiated (a) by one child, (b) by collaborative agreement, or (c) by an adult
      authority figure. In the group games with a rule initiated by one child, children
      attributed ability to change rules only to that individual and not his or her
      friends, and they mentioned ownership and authority in their explanations. When
      the rule was initiated collaboratively, older children said that no individual
      could change the rule, whereas younger children said that either individual could
      do so. When an adult initiated the rule, children stated that only the adult
      could change it. In contrast, children always endorsed a child's decision to
      change his or her own solitary rule and never endorsed any child's ability to
      change moral and conventional rules in daily life. Age differences corresponded
      to beliefs about friendship and agreement in peer play (Study 2) and disappeared
      when the decision process behind and normative force of collaboratively initiated
      rules were clarified (Study 3). These results show important connections between
      normativity and considerations of authority and collaboration during early
      childhood.

PMID- 28495208
TI  - Presence of Viral microRNA in Extracellular Environments.

PMID- 28495210
TI  - 3 Tesla 23Na Magnetic Resonance Imaging During Acute Kidney Injury.
AB  - RATIONALE AND OBJECTIVES: Sodium and proton magnetic resonance imaging (23Na/1H
      MRI) have shown that muscle and skin can store Na+ without water. In chronic
      renal failure and in heart failure, Na+ mobilization occurs, but is variable
      depending on age, dialysis vintage, and other features. Na+ storage depots have
      not been studied in patients with acute kidney injury (AKI). MATERIALS AND
      METHODS: We studied 7 patients with AKI (mean age: 51.7 years; range: 25-84) and
      14 age-matched and gender-matched healthy controls. All underwent 23Na/1H-MRI at
      the calf. Patients were studied before and after acute hemodialysis therapy
      within 5-6 days. The 23Na-MRI produced grayscale images containing Na+ phantoms,
      which served to quantify Na+ contents. A fat-suppressed inversion recovery
      sequence was used to quantify H2O content. RESULTS: Plasma Na+ levels did not
      change. Mean Na+ contents in muscle and skin did not significantly change
      following four to five cycles of hemodialysis treatment (before therapy: 32.7 +/-
      6.9 and 44.2 +/- 13.5 mmol/L, respectively; after dialysis: 31.7 +/- 10.2 and
      42.8 +/- 11.8 mmol/L, respectively; P > .05). Water content measurements did not
      differ significantly before and after hemodialysis in muscle and skin (P > .05).
      Na+ contents in calf muscle and skin of patients before hemodialysis were
      significantly higher than in healthy subjects (16.6 +/- 2.1 and 17.9 +/- 3.2) and
      remained significantly elevated after hemodialysis. CONCLUSIONS: Na+ in muscle
      and skin accumulates in patients with AKI and, in contrast to patients receiving
      chronic hemodialysis and those with acute heart failure, is not mobilized with
      hemodialysis within 5-6 days.

PMID- 28495211
TI  - Maximum Aortic Valve Opening Phase for Annulus Sizing in Pre-TAVR CTA.
AB  - RATIONALE AND OBJECTIVES: The optimal phase for the measurement of the aortic
      annular area for transcatheter aortic valve replacement (TAVR) is not
      standardized, although most agree that systolic measurements are preferred, when
      the annulus is larger. We hypothesized that the maximum annular area occurs at
      the cardiac phase of the maximum aortic valve opening (MAVO) and that this phase
      can be accurately and reproducibly assessed by visual inspection only. MATERIALS
      AND METHODS: The aortic valve opening area was inspected visually by two readers
      to determine the MAVO phase. The annular area was measured at the MAVO phase and
      the typical systolic phase (35% of the R-R interval). Differences in the annular
      area that would change valve sizing for prostheses were noted. RESULTS: Fifty
      patients (mean age 81) were studied. Ninety percent had the MAVO at the 15%-25% R
      R interval. There was high interobserver correlation (0.89) for determining the
      MAVO phase by visual inspection. For 49 out of 50 patients, the annular area was
      maximal at the MAVO phase. The mean difference in the annular area between the
      MAVO phase and 35% was 22.3 (+/-4.57) mm2. In 12% of the patients, the difference
      in the annular area changed the recommended size of a self-expanding prosthesis
      and would have altered the procedure in 32% for balloon-expandable prostheses.
      CONCLUSIONS: Visually assessed MAVO occurs in early systole for most patients and
      is almost always the cardiac phase of the maximal aortic annular area. This
      method allows rapid and reproducible determination of the appropriate phase for
      TAVR planning measurements. Consideration should be given to optimizing pre-TAVR
      computed tomography acquisitions for early systolic reconstruction and visual
      determination of the MAVO.

PMID- 28495212
TI  - Quantification of Mouse Renal Perfusion Using Arterial Spin Labeled MRI at 1 T.
AB  - RATIONALE AND OBJECTIVES: Quantitative measurement of renal perfusion in murine
      models provides important information on the organ physiology and disease states.
      The 1-T desktop magnetic resonance imaging has a small footprint and a self
      contained fringe field. This resultant flexibility in siting makes the system
      ideal for preclinical imaging research. Our objective was to evaluate the
      capability of the 1-T desktop magnetic resonance imaging to measure mouse renal
      perfusion without the administration of exogenous contrast agents. MATERIALS AND
      METHODS: We implemented a flow-sensitive alternating inversion recovery (FAIR)
      based arterial spin labeling sequence with a mouse volume coil on a 1-T desktop
      magnetic resonance scanner. The validity of the implementation was tested by
      comparing obtained renal perfusion results with literature values for normal mice
      and challenging the technique with mice treated with furosemide, a blood vessel
      vasoconstrictor drug. RESULTS: The measured cortical and medullary perfusions
      were quantified to be 402 +/- 95 and 184 +/- 52 mL/100 g/min, respectively, in
      agreement with literature values. The ratio of cortical to medullary renal blood
      flow was between 2 and 3 and was independent of the mouse weight. As expected,
      upon furosemide injection, a decrease (~50%) in cortical perfusion was observed
      in the mice population, at 1 hour post injection compared to baseline (P <
      0.0001), which returned to baseline after 24 hours (P = 0.68). CONCLUSIONS: We
      reported the successful application of FAIR-based arterial spin labeling for
      noncontrast perfusion measurement of mouse kidneys using a 1-T desktop scanner.
      The easy implementation of FAIR sequence on a 1-T desktop scanner offers the
      potential for longitudinal perfusion studies in limited access areas such as
      behind the barrier in mouse facilities and in multimodality preclinical imaging
      laboratories without the administration of exogenous contrast agents.

PMID- 28495213
TI  - Breast Density Legislation in New England: A Survey Study of Practicing
      Radiologists.
AB  - RATIONALE AND OBJECTIVES: This study aimed to assess radiologists' knowledge
      about breast density legislation as well as perceived practice changes resulting
      from the enactment of breast density legislation. MATERIALS AND METHODS: This is
      an institutional review board-exempt anonymous email survey of 523 members of the
      New England Roentgen Ray Society. In addition to radiologist demographics, survey
      questions addressed radiologist knowledge of breast density legislation,
      knowledge of breast density as a risk factor for breast cancer, recommendations
      for supplemental screening, and perceived practice changes resulting from density
      notification legislation. RESULTS: Of the 523 members, 96 responded, yielding an
      18% response rate. Seventy-three percent of respondents practiced in a state with
      breast density legislation. Sixty-nine percent felt that breast density
      notification increased patient anxiety about breast cancer, but also increased
      patient (74%) and provider (66%) understanding of the effect of breast density on
      mammographic sensitivity. Radiologist knowledge of the relative risk of breast
      cancer when comparing breasts of different density was variable. CONCLUSIONS:
      Considerable confusion and controversy regarding breast density persists, even
      among practicing radiologists.

PMID- 28495214
TI  - Lesson Learned with the Use of Iliac Branch Devices: Single Centre 10 Year
      Experience in 157 Consecutive Procedures.
AB  - OBJECTIVE/BACKGROUND: Absence of an adequate iliac seal rarely represents an
      absolute contraindication to endovascular abdominal aortic aneurysm repair. Iliac
      branch devices (IBD) are increasingly used in patients with extensive aorto-iliac
      aneurysmal disease, but few data are available on the long-term results of these
      procedures. METHODS: Between 2006 and 2016, 157 consecutive IBD procedures
      performed at a single centre were entered into a prospective database.
      Indications included unilateral or bilateral common iliac artery aneurysms
      combined or not with abdominal aortic aneurysms. Long-term results were reported
      according to the Kaplan-Meier method. RESULTS: During the study period 149
      patients were treated with an iliac branched endograft. Isolated IBD was
      implanted in 17.8% of the cases; technical success rate was 97.5%. Peri-operative
      procedure failure occurred in seven patients, four during surgery and three
      within 30 days of the procedure. Presence of ipsilateral hypogastric aneurysm (p
      = .031; Exp [B] = 6.72) and intervention performed during the initial study
      period (p = .006; Exp [B] = 10.40) were predictive of early failure on
      multivariate analysis. After a mean follow-up of 44.2 months actuarial freedom
      from IBD related re-intervention was 97.4%, 95.6%, 94.0%, and 91.8% at 1, 3, 5,
      and 9 years, respectively. Hypogastric artery patency was 94.7%, 92.6%, and 90.4%
      at 1, 3, and 10 years, respectively. Presence of a hypogastric aneurysm was an
      independent predictor of target artery occlusion during follow-up on multivariate
      analysis (p = .007; Exp [B] = 5.93). CONCLUSION: Iliac branched endografting can
      now be performed with a high technical success rate; long-term freedom from re
      intervention is comparable with patients treated with standard aortic
      endografting. IBD should be considered a first-option treatment in patients with
      adequate vascular anatomy unsuitable for standard endovascular aortic repair.

PMID- 28495215
TI  - Vertebral Penetration of an Inferior Vena Cava Filter.

PMID- 28495216
TI  - What it should mean for an algorithm to pass a statistical Turing test for
      detection of epileptiform discharges.

PMID- 28495217
TI  - Individuals with mild MS with poor sleep quality have impaired visuospatial
      memory and lower perceived functional abilities.
AB  - BACKGROUND: Sleep disturbances are common in individuals with Multiple Sclerosis
      (MS), but the impact of poor sleep quality on cognitive and physical function in
      individuals with MS is less clear. OBJECTIVE/HYPOTHESIS: The purpose of this
      study was to examine the relationship between sleep quality and cognitive and
      physical function in individuals with mild MS. METHODS: Forty individuals with
      relapsing-remitting or secondary-progressive MS (50.3 +/- 11.6 years of age)
      participated. The Pittsburgh Sleep Quality Index (PSQI) was used to index sleep
      quality. A PSQI of <=5 was considered good sleep quality and >5 was considered
      poor sleep quality. Cognitive function was assessed using a battery of cognitive
      tests, and physical function was assessed using 2 objective measures and a self
      report measure. RESULTS: Thirteen individuals (32.5%) indicated good sleep
      quality and 27 (67.5%) of the participants reported poor sleep quality. Those
      with good sleep quality performed significantly better on a visuospatial memory
      test (p = 0.025) and reported higher functional abilities (p < 0.001) compared to
      those with poor sleep quality. There was no difference in performance on the
      cognitive tests of verbal memory, information processing, or executive function,
      or the objective function measures. Individuals with poor sleep quality had
      higher levels of fatigue, depression, and anxiety, and lower quality of life.
      CONCLUSIONS: Visuospatial memory appears to be the memory domain particularly
      associated with poor sleep quality in people with mild MS. Also, individuals with
      mild MS with poor sleep quality may underestimate their functional abilities.

PMID- 28495218
TI  - Effects of hippocampal low-frequency stimulation in idiopathic non-human primate
      epilepsy assessed via a remote-sensing-enabled neurostimulator.
AB  - Individuals with pharmacoresistant epilepsy remain a large and under-treated
      patient population. Continued technologic advancements in implantable
      neurostimulators have spurred considerable research efforts directed towards the
      development of novel antiepileptic stimulation therapies. However, the lack of
      adequate preclinical experimental platforms has precluded a detailed
      understanding of the differential effects of stimulation parameters on neuronal
      activity within seizure networks. In order to chronically monitor seizures and
      the effects of stimulation in a freely-behaving non-human primate with idiopathic
      epilepsy, we employed a novel simultaneous video-intracranial EEG recording
      platform using a state-of-the-art sensing-enabled, rechargeable clinical
      neurostimulator with real-time seizure detection and wireless data streaming
      capabilities. Using this platform, we were able to characterize the
      electrographic and semiologic features of the focal-onset, secondarily
      generalizing tonic-clonic seizures stably expressed in this animal. A series of
      acute experiments exploring low-frequency (2Hz) hippocampal stimulation
      identified a pulse width (150MUs) and current amplitude (4mA) combination which
      maximally suppressed local hippocampal activity. These optimized stimulation
      parameters were then delivered to the seizure onset-side hippocampus in a series
      of chronic experiments. This long-term testing revealed that the suppressive
      effects of low-frequency hippocampal stimulation 1) diminish when delivered
      continuously but are maintained when stimulation is cycled on and off, 2) are
      dependent on circadian rhythms, and 3) do not necessarily confer seizure
      protective effects.

PMID- 28495219
TI  - Increases in Use and Activity Due to Urban Renewal: Effect of a Natural
      Experiment.
AB  - INTRODUCTION: Urban green space and other recreational facilities are associated
      with physical activity. For adolescents living in multistory housing, public
      outdoor spaces that support physical activity may play an important role in
      activity promotion strategies. However, stronger evidence for a relation between
      the built environment and adolescent physical activity is scarce. DESIGN: A
      natural experiment with a pre-experimental design was used with data collected in
      2010 and 2012 before and after an urban renewal. Data were analyzed in 2016.
      SETTING/PARTICIPANTS: Adolescents aged 11-16 years spending a minimum of 10
      minutes daily within a 400-m buffer of the renewal district were included in the
      analyses, resulting in 354 adolescents at baseline and 319 post-renewal.
      INTERVENTION: A multicomponent urban renewal project of approximately 35 million
      Euros in a disadvantaged neighborhood in the capital of Denmark occurred between
      2010 and 2012. MAIN OUTCOME MEASURES: The main outcomes were changes in time
      spent and physical activity within the area among adolescents, measured by
      accelerometry (ActiGraph GT3X) and GPS devices (Qstarz BT-Q1000XT). RESULTS: Time
      spent in the area was greater in 2012 than 2010 with an additional 24.6 minutes
      per day (p=0.017). Of this time, 7.8 minutes were spent in light and 4.5 minutes
      in moderate to vigorous physical activity. CONCLUSIONS: The present study
      indicates that a multicomponent urban renewal strategy in a disadvantaged
      district has the potential to increase time spent and physical activity in the
      district for adolescents living in or close to the district.

PMID- 28495220
TI  - Other Tobacco Product Use Among Sexual Minority Young Adult Bar Patrons.
AB  - INTRODUCTION: Lesbian, gay, and bisexual (LGB) individuals smoke at rates 1.5-2
      times higher than the general population, but less is known about LGB consumption
      of other tobacco products (OTPs) and gender differences. OTP use among young
      adult LGB bar patrons and the relationship among past quit attempts, intention to
      quit, and binge drinking with OTP use was examined. METHODS: A cross-sectional
      survey of young adults (aged 18-26) in bars/nightclubs in seven U.S. cities
      between 2012 and 2014 (N=8,010; 1,101 LGB participants) was analyzed in 2016.
      Logistic regressions examined current use of five OTPs (cigarillos, electronic
      cigarettes, hookah, chewing tobacco, and snus) and sexual minority status,
      adjusting for demographics and comparing LB women and GB men with their
      heterosexual counterparts. RESULTS: LGB bar/nightclub patrons used all OTPs more
      than their heterosexual counterparts. LB women were more likely than heterosexual
      women to use cigarillos, electronic cigarettes, hookah, chew, and snus. GB men
      were more likely than heterosexual men to smoke cigarillos, electronic
      cigarettes, hookah, and use chew and snus. Past-year quit attempt was associated
      with increased odds of electronic cigarette use in men and women, and increased
      odds of dual use (cigarettes and OTPs) among men. Intention to quit was
      negatively associated with dual use among women. Binge drinking was associated
      with increased use of all OTPs across genders. CONCLUSIONS: LGB bar-going young
      adults are at higher risk for OTP use than their heterosexual counterparts. Bar
      based interventions are needed to address all forms of tobacco use in this high
      risk group.

PMID- 28495221
TI  - Impact of Provider Recommendation on Tdap Vaccination of Adolescents Aged 13-17
      Years.
AB  - INTRODUCTION: Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination has
      been recommended for adolescents in the U.S. since 2006. Information on Tdap
      vaccination by provider recommendation is limited. The purpose of this study is
      to assess recent Tdap vaccination by provider recommendation status among
      adolescents aged 13-17 years. METHODS: The 2013 National Immunization Survey-Teen
      data (N=18,948) were analyzed in 2016 to assess national and state-specific Tdap
      vaccination coverage disparities among adolescents by provider recommendation
      status, and other demographic and access to care variables. Multivariable
      logistic regression analysis and predictive marginal modeling evaluated
      associations between Tdap vaccination and provider recommendation status and
      other factors among adolescents aged 13-17 years. RESULTS: Overall, only 56.9% of
      adolescents aged 13-17 years received a provider recommendation for Tdap.
      Coverage was significantly higher among adolescents with a provider
      recommendation (88.6%) compared with those without a provider recommendation
      (80.5%) (p<0.05). Multivariable logistic regression showed that characteristics
      independently associated with a higher likelihood of Tdap vaccination included
      receiving a provider recommendation, Hispanic ethnicity, having two to three
      physician contacts in the past 12 months, having one or two vaccination
      providers, and receiving vaccinations from more than one type of facility
      (p<0.05). CONCLUSIONS: Provider recommendations were significantly associated
      with Tdap vaccination among adolescents aged 13-17 years. However, 43% of parents
      of adolescents did not receive a provider recommendation. Evidence-based
      strategies such as standing orders and provider reminders alone or health systems
      interventions in combination should be taken to improve provider recommendation
      and Tdap vaccination coverage.

PMID- 28495222
TI  - Job Characteristics Associated With Self-Rated Fair or Poor Health Among U.S.
      Workers.
AB  - INTRODUCTION: Approximately 60% of the U.S. adult population is employed. Many
      aspects of a person's job may influence health, but it is unclear which job
      characteristics are most strongly associated with health at a population level.
      The purpose of this study was to identify important associations between job
      characteristics and workers' self-rated health in a nationally representative
      survey of U.S. workers. METHODS: Data from the 2010 National Health Interview
      Survey were used to calculate weighted prevalence rates for self-reported
      fair/poor health for five categories of job characteristics: occupation;
      pay/benefits (economic); work organization; chemical/environmental hazards; and
      psychosocial factors. Backward elimination methods were used to build a
      regression model for self-reported health with the significant job
      characteristics, adjusting for sociodemographic variables and health behaviors.
      Data were collected in 2010 and analyzed in 2012-2016. RESULTS: After adjusting
      for covariates, workers were more likely to have fair/poor health if they were
      employed in business operations occupations (e.g., buyers, human resources
      workers, event planners, marketing specialists; adjusted prevalence ratio
      [APR]=1.85, 95% CI=1.19, 2.88); had no paid sick leave (APR=1.35, 95% CI=1.11,
      1.63); worried about becoming unemployed (APR=1.43, 95% CI=1.22, 1.69); had
      difficulty combining work and family (APR=1.23, 95% CI=1.01, 1.49); or had been
      bullied/threatened on the job (APR=1.82, 95% CI=1.44, 2.29). CONCLUSIONS:
      Occupation, lack of paid sick leave, and multiple psychosocial factors were
      associated with fair/poor health among U.S. workers at the population level in
      2010. Public health professionals and employers should consider these factors
      when developing interventions to improve worker health.

PMID- 28495223
TI  - Feasibility of Text Message Influenza Vaccine Safety Monitoring During Pregnancy.
AB  - INTRODUCTION: The feasibility and accuracy of text messaging to monitor events
      after influenza vaccination throughout pregnancy and the neonatal period has not
      been studied, but may be important for seasonal and pandemic influenza vaccines
      and future maternal vaccines. METHODS: This prospective observational study was
      conducted during 2013-2014 and analyzed in 2015-2016. Enrolled pregnant women
      receiving inactivated influenza vaccination at a gestational age <20 weeks were
      sent text messages intermittently through participant-reported pregnancy end to
      request fever, health events, and neonatal outcomes. Text message response rates,
      Day 0-2 fever (>=100.4 degrees F), health events, and birth/neonatal outcomes
      were assessed. RESULTS: Most (80.2%, n=166) eligible women enrolled. Median
      gestational age was 8.9 (SD=3.9) weeks at vaccination. Response rates remained
      high (80.0%-95.2%). Only one Day 0-2 fever was reported. Women reported via text
      both pregnancy- and non-pregnancy-specific health events, not all associated with
      medical visits. Most pregnancy-specific events in the electronic medical record
      (EMR) were reported via text message. Of all enrollees, 84.9% completed the study
      (131 reported live birth, ten reported pregnancy loss). Two losses reported via
      text were not medically attended; there was one additional EMR-identified loss.
      Gestational age and weight at birth were similar between text message-reported
      and EMR-abstracted data and 95% CIs were overlapping for proportions of
      prematurity, low birth weight, small for gestational age, and major birth
      defects, as identified by text message-reported versus EMR-abstracted plus text
      message-reported versus EMR-abstracted data only. CONCLUSIONS: This study
      demonstrated the feasibility of text messaging for influenza vaccine safety
      surveillance sustained throughout pregnancy. In these women receiving inactivated
      influenza vaccination during pregnancy, post-vaccination fever was infrequent and
      a typical pattern of maternal and neonatal health outcomes was observed.

PMID- 28495224
TI  - A solid swing and ... contact [or miss]? Commentary on "Towards a Grand Unified
      Theory of sports performance".

PMID- 28495225
TI  - Detection and molecular status of Isospora sp. from the domestic pigeon (Columba
      livia domestica).
AB  - The domestic pigeon, Columba livia domestica, is reared for meat production, as a
      pet, or for racing. Few reports have characterized the parasitic protists from
      the genus Isospora isolated from Columbiformes. We detected Isospora-like oocysts
      from C. livia reared for racing. The oocyst contained two sporocysts, and each
      sporocyst included four sporozoites. The sporulated oocysts (n=4) were spherical;
      their mean diameters were 25.6 (24.0-27.2)*24.7 (23.4-26.0) MUm. Micropyles,
      polar granules, and oocyst residuum were absent. The mean length and width of the
      sporocysts (n=8) were 19.5 (18.5-20.5) and 11.2 (10.2-12.1) MUm, respectively.
      Stieda and sub-Stieda bodies were observed. Single-oocyst PCR revealed two
      different 18S rRNA gene sequences and one 28S rRNA gene sequence in a single
      oocyst of Isospora sp. Based on a phylogenetic analysis of the 18S rRNA gene, the
      two sequences made a group which fell within a cluster of known avian Isospora
      species. A tree based on the 28S rRNA gene sequence indicated that sequences from
      the pigeon Isospora sp. fell within a cluster of avian Isospora species. Both
      trees failed to clarify the phylogenetic relationships among the avian Isospora
      species due to limited resolution. Because the morphological description of
      Isospora sp. is based on only four oocysts, Isospora sp. is not proposed as a
      novel species here. This is the first description of Isospora sp. isolated from
      the domestic pigeon C. livia.

PMID- 28495226
TI  - A gas flow model for layered landfills with vertical extraction wells.
AB  - This paper developed a two-dimensional axisymmetric analytical model for layered
      landfills with vertical wells. The model uses a horizontal layered structure to
      describe the waste non-homogeneity with depth in gas generation, permeability and
      temperature. The governing equations in the cylindrical coordinate system were
      transformed to dimensionless forms and solved using a method of eigenfunction
      expansion. After verification, the effects of different well boundary conditions
      and gas extraction systems on recovery efficiency were investigated. A
      dimensionless double-layer system, consisting of a cover and a waste layer, was
      also explored. The results show that a constant vacuum pressure boundary
      condition can be enough to describe a perforated pipe surrounded by drainage
      gravel with a reasonable value of well radius, such as half the radius of gravel
      fill. Also, the 7 independent variables (one marked with an asterisk is
      dimensionless) of a double-layer system can be integrated into 3 dimensionless
      ones: Cover permeability Kv1*/(Vertical gas permeability of waste Kv2**Cover
      thickness h1*),-Vacuum pressure pw*PatmKv2*/(MURgT2*Gas generation rate of waste
      s2) and ln(Well radius rw*)/(Anisotropy degree of waste k2*). The integration is
      based on the inherent mechanism of this flow system with certain simplification.
      The effects of these variables are then quantitatively characterized for a better
      understanding of gas recovery efficiency. Same recovery efficiency can be
      achieved with different variable combinations. For example, increasing h1* (such
      as doubling it) has the same effect with decreasing Kv1* (such as halving it).
      Along with the reduction of variables by half, the integration can facilitate the
      preliminary design, and is a small but important advance in the consideration of
      MSW non-homogeneity.

PMID- 28495227
TI  - Lab-scale co-digestion of kitchen waste and brown water for a preliminary
      performance evaluation of a decentralized waste and wastewater management.
AB  - An overall interaction is manifested between wastewater and solid waste
      management schemes. At the Laboratory of Environmental Engineering (LISA) of the
      University of Padova, Italy, the scientific and technical implications of putting
      into practice a decentralized waste and wastewater treatment based on the
      separation of grey water, brown water (BW - faecal matter) and yellow water (YW -
      urine) are currently undergoing investigation in the Aquanova Project. An
      additional aim of this concept is the source segregation of kitchen waste (KW)
      for subsequent anaerobic co-digestion with BW. To determine an optimal mixing
      ratio and temperature for use in the treatment of KW, BW, and eventually YW, by
      means of anaerobic digestion, a series of lab-scale batch tests were performed.
      Organic mixtures of KW and BW performed much better (max. 520mlCH4/gVS) in terms
      of methane yields than the individual substrates alone (max. 220mlCH4/gVS). A
      small concentration of urine proved to have a positive effect on anaerobic
      digestion performance, possibly due to the presence of micronutrients in YW. When
      considering high YW concentrations in the anaerobically digested mixtures, no
      ammonia inhibition was observed until a 30% and 10% YW content was added under
      mesophilic and thermophilic conditions, respectively.

PMID- 28495228
TI  - Post-operative spondylodiscitis due to Propionibacterium acnes: A case report.
AB  - Post-operative spondylodiscitis due to Propionibacterium acnes is rare, with only
      a few cases reported in the literature. In this article, we report the case of a
      76-year-old patient who suffered from spondylodiscitis T12-L1 discovered after 1
      month of pain and fever. Antibiotic treatment was administered for 6 weeks
      without revision surgery. Diagnosis remains incomplete, and preventive therapy
      against this infection is not well known. There is no link between
      immunosuppression and this infection. A cure has been reported in 98% of cases,
      but further investigation is still required for the establishment of treatment
      guidelines.

PMID- 28495229
TI  - Intramedullary epidermoid cysts in adults: Case report and updated literature
      review.
AB  - Epidermoid cysts are classical tumors in neurosurgery, but spinal locations are
      rare and intramedullary locations represent only approximately 80 cases in the
      literature. Intramedullary epidermoid cysts arise from ectodermic tissue
      inclusion during neural tube closure. Intramedullary epidermoid cysts are more
      frequent in young patients and in a thoracic location. We report the case of a 61
      year-old patient consulting for bilateral asymmetrical progressive paraparesis
      and proprioceptive ataxia revealing a T3-T4 exophytic medullar epidermoid cyst.
      The tumor was surgically removed with a favorable outcome. The capsule was
      partially removed. The authors present an updated literature review of
      intramedullary epidermoid cyst diagnosis, management and recommendations.

PMID- 28495230
TI  - Electrocardiogram voltage discordance: Interpretation of low QRS voltage only in
      the precordial leads.
AB  - OBJECTIVES: To define clinical correlates of low voltage isolated to precordial
      leads on the surface electrocardiogram (ECG). INTRODUCTION: Low voltage (V) on
      the ECG is defined as QRS V<5mm in all limb leads and <10mm in all precordial
      leads. The diagnostic use of ECGs with low voltage isolated to the precordial
      leads with normal limb lead voltages is unclear. METHODS: Twelve-lead ECGs with
      QRS V>5mm in one or more limb leads and <10mm in all precordial leads were
      collected. Associated clinical conditions were determined from clinical data,
      echocardiograms, and chest radiographs. RESULTS: Low precordial voltage was found
      in 256 of 150,000 ECGs (~0.2%). 50.4% of patients had discordant ECGs that
      correlated with classic etiologies, with a higher incidence of LV dilation in
      those with classic etiologies than those without. CONCLUSION: Low precordial
      voltage is associated with classic etiologies and LV dilation.

PMID- 28495231
TI  - Descriptive study of the parkinsonian population in the north of France:
      Epidemiological analysis and healthcare consumption.
AB  - BACKGROUND: The "neurodegenerative diseases plan" under elaboration for the Hauts
      de-France region requires better knowledge of the patient population and care
      pathways. In France, the prevalence of Parkinson's disease (PD) has been
      estimated from cohorts to be about 1-3 per 1000 inhabitants, but exhaustive data
      are scarce for the general population. The purpose of this study was to evaluate
      the prevalence of PD in the Hauts-de-France region and to assess PD-related
      healthcare consumption. METHOD: A descriptive study was conducted to identify the
      parkinsonian population in the Hauts-de-France region (including the
      administrative districts of Pas-de-Calais and Picardie) for the year 2014.
      Parkinsonian patients were identified from health insurance fund reimbursement
      data using the following criteria: (i) reimbursement for a PD-specific
      medication; (ii) attribution of long-duration disease status coded as PD; (iii)
      hospital stay with PD diagnosis in the standard discharge report contained in the
      French medico-economic database on hospital activity (PMSI). RESULTS: The raw
      prevalence of PD in the region was 5.03 per 1000 inhabitants aged 20 years and
      older. The standardized prevalence by health territory ranged from 4.0 to 9.0 per
      1000 inhabitants aged 20 years and older. During the 1-year study period, 33.5%
      of patients had a neurology consultation, 57.1% attended a physiotherapy session,
      and 7.7% received speech therapy. Most of patients (79.6%) were treated with
      levodopa, sometimes in combination with a catechol-O-methyl transferase inhibitor
      (14.4%). Dopaminergic agonists were prescribed in 33.5% of cases. A neuroleptic
      was prescribed for 6.9% of the population (clozapine for 25.9%). CONCLUSION: The
      prevalence of PD is high in the Hauts-de-France region with a heterogeneous
      distribution by health territory. Neurology consultations were attended by a
      minority of patients in 2014. This work provides perspectives for necessary
      improvement in specialized care for this disease, both in terms of follow-up
      consultations and home care.

PMID- 28495232
TI  - Management and outcome of cerebral venous thrombosis after head trauma: A case
      series.
AB  - Cerebral venous thrombosis (CVT) is an underdiagnosed complication of head
      trauma. To date, initiation of anticoagulation is still a matter of debate
      because of the risk of worsening traumatic hemorrhage. This report describes a
      case series of five patients admitted for head injury complicated by CVT. The
      main associated radiological signs were skull fractures crossing the venous sinus
      and adjacent traumatic hematoma. In four patients, anticoagulation was introduced
      within 48-72h of CVT diagnosis, with no subsequent hemorrhagic complications. The
      present report and data from the literature raise the question of systematic
      additional venoscans when confronted by associated radiological features of post
      traumatic CVT. The safety of anticoagulation in selected patients is also
      discussed.

PMID- 28495233
TI  - Sorption and speciation of iodine in groundwater system: The roles of organic
      matter and organic-mineral complexes.
AB  - Characterizing the properties of main host of iodine in soil/sediment and the
      geochemical behaviors of iodine species are critical to understand the mechanisms
      of iodine mobilization in groundwater systems. Four surface soil and six
      subsurface sediment samples were collected from the iodine-affected area of
      Datong basin in northern China to conduct batch experiments and to evaluate the
      effects of NOM and/or organic-mineral complexes on iodide/iodate geochemical
      behaviors. The results showed that both iodine contents and kf-iodate values had
      positive correlations with solid TOC contents, implying the potential host of NOM
      for iodine in soil/sediment samples. The results of chemical removal of easily
      extracted NOM indicated that the NOM of surface soils is mainly composed of
      surface embedded organic matter, while sediment NOM mainly occurs in the form of
      organic-mineral complexes. After the removal of surface sorbed NOM, the decrease
      in kf-iodate value of treated surface soils indicates that surface sorbed NOM
      enhances iodate adsorption onto surface soil. By contrast, kf-iodate value
      increases in several H2O2-treated sediment samples, which was considered to
      result from exposed rod-like minerals rich in Fe/Al oxyhydroxide/oxides. After
      chemical removal of organic-mineral complexes, the lowest kf-iodate value for
      both treated surface soils and sediments suggests the dominant role of organic
      mineral complexes on controlling the iodate geochemical behavior. In comparison
      with iodate, iodide exhibited lower affinities on all (un)treated soil/sediment
      samples. The understanding of different geochemical behaviors of iodine species
      helps to explain the occurrence of high iodine groundwater with iodate and iodide
      as the main species in shallow (oxidizing conditions) and deep (reducing
      conditions) groundwater.

PMID- 28495234
TI  - Oxidative stress-induced Akt downregulation mediates green tea toxicity towards
      prostate cancer cells.
AB  - Green tea consumption has been shown to possess cancer chemopreventive activity.
      Polyphenol E (PE) is a widely used standardized green tea extract formulation.
      This study was designed to investigate the impact of PE on prostate cancer cells
      (PC3), analyze the potential signals involved and elucidate whether anti- or pro
      oxidant effects may be implicated. Treatment of PC3 cells with 30 and 100MUg/ml
      PE significantly decreased cell viability and proliferation. At the tested
      concentrations, PE did not exert any antioxidant activity, eliciting instead a
      pro-oxidant effect at concentrations 30 and 100MUg/ml, which was consistent with
      the observed PE cytotoxicity. PE-induced cell death was associated with
      mitochondrial dysfunction and downregulation of Akt activation, thus suggesting
      their implication in the PE-elicited cell dysfunction. Cell exposure to the ROS
      scavenger N-Acetyl Cysteine prevented PE-induced ROS increase, pAkt impairment,
      and cell death, clearly indicating the causative role of ROS in the observed
      phenomena. Failure of PE to induce PC3 damage in cells overexpressing Akt further
      confirms its implication in the PE-elicited cell death. Our findings showed an
      association between the antiproliferative and the pro-oxidant effect elicited by
      PE on PC3 cells and delineates a molecular signaling pattern potentially
      implicated in the toxicity of PE towards prostate cancer cells.

PMID- 28495235
TI  - Prenatal detection of megacystis: not always an adverse prognostic factor.
      Experience in 25 consecutive cases in a tertiary referral center, with complete
      neonatal outcome and follow-up.
AB  - INTRODUCTION: Megacystis is a condition of abnormal enlarged fetal bladder for
      gestational age, which is usually associated with urological malformations that
      may constitute a life-threatening condition for the baby. OBJECTIVE: The purpose
      of this study was to assess the prognostic and etiological criteria of fetal
      megacystis and to describe the neonatal outcome in a large series collected in a
      single tertiary center. STUDY DESIGN: A retrospective observational study was
      conducted between 2008 and 2012. We reviewed all consecutive cases of fetal
      megacystis diagnosed during routine ultrasound (US) screening. The following data
      were collected and analyzed: maternal age, gestational age at diagnosis, prenatal
      ultrasonographic details of the urinary system, extra-urinary ultrasonographic
      anomalies, fetal karyotype, pregnancy outcome, postnatal diagnosis, and
      medical/surgical follow-up. RESULTS: Of the 25 fetuses included in this study,
      76% were males. The mean gestational age (GA) at diagnosis was 23.1 +/- 7.5 weeks
      (range 12-34), among them only four (16%) were diagnosed during the first
      trimester. Associated urological malformations were detected in 92% (n = 23) of
      the cases, while other malformations were detected in 36% (n = 9).
      Oligohydramnios or anyhydramnios were observed in 52% (n = 13) of the cases.
      Twelve (48%) fetuses were considered as having poor prognosis for renal function.
      Vesicocentesis with or without vesico-amniotic infusion were performed in 28% (n
      = 7) of the cases. Pregnancy outcome was surprisingly good, with only one case of
      prenatal death and survival rate of 96% (n = 24) of liveborn babies. Posterior
      urethral valve (PUV) (n = 9, 36%) was the most common etiology of the fetal
      megacystis, followed by persistent urogenital sinus (n = 2, 8%), Prune belly
      syndrome (n = 2, 8%) and bilateral vescico-ureteral reflux (VUR) (n = 2, 8%).
      Surgical or endoscopic procedures were performed in 75% (n = 18) of the cases.
      Six (24%) newborns presented with moderate/severe respiratory distress that
      requested invasive assisted ventilation. Three cases (n = 3, 12%) of perinatal
      death were observed due to severe impaired renal function. After a median follow
      up of 29 months renal function was good in 79% (n = 19) of the cases.
      CONCLUSIONS: Fetal megacystis may underline a wide range of associated
      pathologies with the highest prevalence of urinary malformation. Optimal
      counseling of the involved parents requires a multidisciplinary approach to allow
      the best management during the pregnancy and the perinatal period. Despite the
      high risk of renal failure, lung hypoplasia, and severe associated anomalies, the
      outcome of fetuses with megacystis could be improved thanks to an appropriate
      perinatal diagnosis and neonatal management.

PMID- 28495236
TI  - Fireworks type, injury pattern, and permanent impairment following severe
      fireworks-related injuries.
AB  - BACKGROUND: There is a paucity of clinical data on severe fireworks-related
      injuries, and the relationship between firework types, injury patterns, and
      magnitude of impairment is not well understood. Our objective was to describe the
      relationship between fireworks type, injury patterns, and impairment. METHODS:
      Retrospective case series (2005-2015) of patients who sustained consumer
      fireworks-related injuries requiring hospital admission and/or an operation at a
      Level 1 Trauma/Burn Center. Fireworks types, injury patterns (body region, injury
      type), operation, and permanent impairment were examined. RESULTS: Data from 294
      patients 1 to 61years of age (mean 24years) were examined. The majority (90%)
      were male. 119 (40%) patients were admitted who did not undergo surgery, 163
      (55%) patients required both admission and surgery, and 12 (5%) patients
      underwent outpatient surgery. The greatest proportion of injuries was related to
      shells/mortars (39%). There were proportionally more rocket injuries in children
      (44%), more homemade firework injuries in teens (34%), and more shell/mortar
      injuries in adults (86%). Brain, face, and hand injuries were disproportionately
      represented in the shells/mortars group. Seventy percent of globe-injured
      patients experienced partial or complete permanent vision loss. Thirty-seven
      percent of hand-injured patients required at least one partial or whole
      finger/hand amputation. The greatest proportion of eye and hand injuries
      resulting in permanent impairment was in the shells/mortars group, followed by
      homemade fireworks. Two patients died. CONCLUSIONS: Severe fireworks-related
      injuries from homemade fireworks and shells/mortars have specific injury
      patterns. Shells/mortars disproportionately cause permanent impairment from eye
      and hand injury.

PMID- 28495237
TI  - Multigene panels in Ashkenazi Jewish patients yield high rates of actionable
      mutations in multiple non-BRCA cancer-associated genes.
AB  - OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi
      Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the
      medical records for all patients who underwent multigene panel testing and
      targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical
      actionability for identified pathogenic mutations was characterized based on the
      National Comprehensive Cancer Network (NCCN) guidelines and consensus statements
      and expert opinion for genes not addressed by these guidelines. RESULTS: Four
      hundred and fifty-four patients underwent multigene panel screening, including
      138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three
      hundred and fifty-four patients (78%) had a personal history of cancer. Two
      hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine
      cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and
      291 variants of uncertain significance in 196 patients. Among the 56 patients
      with mutations, 51 (91%) had actionable mutations. Twenty mutations were
      identified by multigene panels among Ashkenazi Jewish patients, 18 of which were
      in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over
      the same study period included 103 patients and identified six mutations in
      BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi
      Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of
      which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2
      genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a
      pressing need to understand how this testing will affect patient management.
      While traditionally many Ashkenazi Jewish patients have undergone targeted
      BRCA1/2 testing, our data suggest consideration of multigene panels in this
      population as the majority of the results are clinically actionable and often in
      genes other than BRCA1/2.

PMID- 28495238
TI  - Uncovering the role of nuclear Lysyl oxidase (LOX) in advanced high grade serous
      ovarian cancer.
AB  - OBJECTIVE: Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of
      collagen and elastin in the extracellular matrix, thus controlling the tensile
      strength of tissues. Along with this primary function, there are evidences
      supporting a role for LOX in many critical biological functions, including gene
      expression regulation, cell growth, adhesion and migration. Accordingly, recent
      studies have supported a pivotal role for LOX in cancer progression and
      metastasis. The current study aimed at investigating the prognostic significance
      and the functional role of intracellular LOX in ovarian cancer. METHODS: To this
      end, we analyzed LOX expression by immunohistochemistry in archived tumor
      material from advanced high grade serous ovarian cancer (HGSOC) patients (n=70)
      and correlated data with clinicopathological parameters and with response to
      chemotherapy. In vitro experiments were also used to investigate the functional
      consequences of LOX expression on behavioral aspects of HGSOC cells. RESULTS: Our
      results showed that nuclear LOX expression is associated with unfavorable outcome
      in advanced HGSOC, being an independent prognostic factor for disease recurrence.
      Besides, high nuclear levels were seen to be associated with resistance to first
      line chemotherapy. Through gene expression modulation experiments in HGSOC cell
      lines, we demonstrate that LOX positively regulates cell proliferation, migration
      and anchorage-independent growth. CONCLUSIONS: Collectively, our data suggest
      that LOX functions as a tumor promoter in HGSOC and positively regulates several
      aspects of the metastatic cascade.

PMID- 28495239
TI  - Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian
      cancer.
AB  - OBJECTIVE: The presence of miliary disease during initial ovarian cancer
      debulking may reflect a distinct mode of peritoneal spread independent from size
      based tumor staging and may explain variation in response to treatment and
      survival outcomes. To infer the prevalence, presentation and clinical
      implications of miliary disease we reviewed existing surgical records. METHODS:
      Reports were available for 1008 primary debulking surgeries for ovarian, primary
      peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005
      to 2015). Clinical outcome data was available for 938 patients. We analyzed a
      high-stage sub-cohort for survival (N=436). RESULTS: Most records were evaluable
      for miliary disease (761/938); for these, the miliary phenotype was highly
      prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While
      optimal debulking rates were unaffected by miliary disease, total resection (R0)
      rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically
      involved while the omentum, mesentery, bowel, peritoneum and diaphragm were
      affected simultaneously (Spearman rho>0.5). Overall, miliary disease was
      associated with worse progression free survival, overall survival, and time from
      relapse to death independent of stage. Survival effects were particularly strong
      for Stage IV disease where median overall survival varied by over 30months (log
      rank p=0.002). CONCLUSIONS: Miliary disease is an identifiable surgical phenotype
      reflecting a distinct clinical trajectory that adds prognostic information to
      standard disease burden-based staging. These findings should permit further
      retrospective investigation in a wider cohort and prompt the consideration of
      prospective structured operative reporting standards and treatment strategies.

PMID- 28495240
TI  - Risk factors for pulmonary complication following fixation of spine fractures.
AB  - BACKGROUND CONTEXT: Previous studies have suggested pulmonary complications are
      common among patients undergoing fixation for traumatic spine fractures. This
      leads to prolonged hospital stay, worse functional outcomes, and increased
      economic burden. However, only limited prognostic information exists regarding
      which patients are at greatest risk for pulmonary complications. PURPOSE: This
      study aimed to identify factors predictive of perioperative pulmonary
      complications in patients undergoing fixation of spine fractures. STUDY
      DESIGN/SETTING: A retrospective review in a level 1 trauma center was carried
      out. PATIENT SAMPLE: The patient sample comprised 302 patients with spinal
      fractures who underwent operative fixation. OUTCOME MEASURES: The outcome
      measures were postoperative pulmonary complications (physiological and functional
      measures). MATERIALS AND METHODS: Demographic and injury features were recorded,
      including age, gender, body mass index (BMI), American Society of
      Anesthesiologists (ASA) classification, mechanism of injury, injury
      characteristics, and neurologic status. Treatment details, including surgery
      length, timing, and approach were reviewed. Postoperative pulmonary complications
      were recorded after a minimum of 6 months' follow-up. RESULTS: Forty-seven
      pulmonary complications occurred in 42 patients (14%), including pneumonia (35),
      adult respiratory distress syndrome (ARDS) (10), and pulmonary embolism (2).
      Logistic regression found spinal cord injury (SCI) to be most predictive of
      pulmonary complications (odds ratio [OR]=4.4, 95% confidence interval [CI] 1.9
      10.1), followed by severe chest injury (OR 2.7, 95% CI 1.1-6.9), male gender (OR
      2.7, 95% CI 1.1-6.8), and ASA classification (OR 2.3, 95% CI 1.4-4.0). Pulmonary
      complications were associated with significantly longer hospital stays (23.9 vs.
      7.7 days, p<.01), stays in the intensive care unit (ICU) (19.9 vs. 3.4 days,
      p<.01), and increased ventilator times (13.8 days vs. 1.9 days, p<.01).
      CONCLUSIONS: Several factors predicted development of pulmonary complications
      after operative spinal fracture, including SCI, severe chest injury, male gender,
      and higher ASA classification. Practitioners should be especially vigilant for of
      postoperative complications and associated injuries following upper-thoracic
      spine fractures. Future study must focus on appropriate interventions necessary
      for reducing complications in these high-risk patients.

PMID- 28495241
TI  - The natural course of prevertebral soft tissue swelling after anterior cervical
      spine surgery: how long will it last?
AB  - BACKGROUND CONTEXT: Prevertebral soft tissue swelling (PSTS) after anterior
      cervical spine surgery (ACSS) has been regarded as one of the critical
      complications that cause airway obstruction. Still, however, no research has
      dealt with how PSTS returns to presurgery status after ACSS; most recommendations
      are being performed without information about its natural course, focusing on
      acute-phase swelling after surgery. PURPOSE: The study aimed to examine how long
      postsurgery PSTS lasts and when it returns to its presurgery state, and to
      analyze the actual influence of a number of factors to observe the natural
      progress of postsurgery PSTS. STUDY DESIGN/SETTING: This is a prospective
      observational study. PATIENT SAMPLE: The sample included a total of 160 patients
      who underwent ACSS, including anterior cervical discectomy and fusion (ACDF) and
      cervical total disc replacement (TDR). OUTCOME MEASURES: The diameter of PSTS
      measured at each set time point after surgeries was compared with PSTS
      measurements before surgery, and analyzed with factors influencing PSTS. METHODS:
      Anterior and posterior diameters of the anterior soft tissue of C3 (pharyngeal
      airway) and C6 (laryngeal airway) were measured using simple lateral radiography
      before surgery, immediately after surgery, at 2 weeks, 1, 3, 6, and 12 months
      after surgery. The progress of postsurgery PSTS was analyzed according to
      patients' individual characteristics, such as age, gender, weight, body mass
      index (BMI), smoking status, use of antiplatelet therapy, hypertension and
      diabetes mellitus, complaints of dysphagia, along with surgical factors such as
      anesthesia time, operation time, numbers of involved operation segments,
      transfusion, estimated blood loss , and operation method. Multivariable analysis
      by generalized linear mixed model was used to perform additional univariable
      analysis on variables found to be related to PSTS. In addition, to find the
      postsurgery interval at which PSTS naturally stabilizes, repeated measures
      analysis of variance and Bonferroni method were used to perform post-hoc tests.
      There were no sources of funding and no conflicts of interest associated with
      this study. RESULTS: For ACDF, the mean values (95% confidence interval [CI]) of
      PSTS in C3 were 4.38 (4.04~4.71), 10.40 (9.64~11.17), 7.72 (7.10~8.35), 6.24
      (5.74~6.69), 5.43 (5.03~5.82), 5.14 (4.77~5.50), and 4.96 (4.59~5.33) mm at each
      follow-up time, respectively. In C6, the average values (95% CI) of PSTS were
      14.43 (13.96~14.91), 19.18 (18.59~19.77), 17.92 (17.37~18.47), 16.98
      (16.45~17.51), 16.18 (15.67~16.69), 15.95 (15.50~16.40), and 15.49 (15.50~16.40)
      mm. For cervical TDR, the mean values (95% CI) of PSTS in C3 were 3.67
      (3.45~3.89), 8.05 (7.17~8.93), 5.42 (4.92~5.91), 4.57 (4.21~4.92), 4.12
      (3.99~4.36), 4.10 (3.87~4.34), and 3.90 (3.66~4.14) mm at each follow-up time,
      respectively. In C6, the average values (95% CI) of PSTS were 13.61
      (12.96~14.25), 16.51 (15.80~17.21), 15.77 (15.13~16.42), 15.24 (14.61~15.87),
      14.62 (14.01~15.22), 14.52 (13.88~15.17), and 13.94 (13.20~14.68) mm. It is
      discovered that PSTS after surgery returned to presurgery status within 1 to 3
      months in the pharyngeal airway (C3) and within 3 to 6 months in the laryngeal
      airway (C6), and gender, BMI, and surgery method (ACDF) were determined to be the
      factors having influence on PSTS after surgery. CONCLUSIONS: It is necessary to
      pay attention to PSTS and patient conditions after ACSS for at least 1 to 6
      months postsurgery, depending on surgical method and operation levels.

PMID- 28495242
TI  - The association between the Hospital Consumer Assessment of Healthcare Providers
      and Systems (HCAHPS) survey and real-world clinical outcomes in lumbar spine
      surgery.
AB  - BACKGROUND CONTEXT: The patient experience of care as measured by the Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is
      currently used to determine hospital reimbursement. The current literature
      inconsistently demonstrates an association between patient satisfaction and
      surgical outcomes. PURPOSE: To determine whether patient satisfaction with
      hospital experience is associated with better clinical outcomes in lumbar spine
      surgery. STUDY DESIGN: A retrospective cohort study conducted at a single
      institution. PATIENT SAMPLE: A total of 249 patients who underwent lumbar spine
      surgery between 2013 and 2015 and completed the HCAHPS survey. OUTCOME MEASURES:
      Self-reported health status measures, including the EuroQol 5 Dimensions (EQ-5D),
      Pain Disability Questionnaire (PDQ), and visual analog score for back pain (VAS
      BP). METHODS: All patients undergoing lumbar spine surgery between 2013 and 2015
      who completed an HCAHPS survey were studied. Patients were excluded from the
      study if they had been diagnosed with spinal malignancy, scoliosis, or had less
      than 1 year of follow-up. Patients who selected a 9 or 10 overall hospital rating
      (OHR) on HCAHPS were placed in the satisfied group, and the remaining patients
      comprised the unsatisfied group. The primary outcomes of this study include
      patient-reported health status measures such as EQ-5D, PDQ, and VAS-BP. No funds
      were received in support of this study, and the authors report no conflict of
      interest-associated biases. RESULTS: Our study population consisted of 249
      patients undergoing lumbar spine surgery. Of these, 197 (79%) patients selected
      an OHR of 9 or 10 on the HCAHPS survey and were included in the satisfied group.
      The only preoperative characteristics that differed significantly between the
      twogroups were gender, a diagnosis of degenerative disc disease (DDD), heavy
      preoperative narcotic use, and a diagnosis of chronic renal failure. At 1 year
      follow-up, no statistically significant differences in EQ-5D, PDQ, or VAS-BP were
      observed. After using multivariable linear regression models to assess the
      association between patient satisfaction and pre- to 1-year postoperative changes
      in health status measures, selecting a top-box OHR was not found to be
      significantly associated with change in either EQ-5D (beta=0.055 [95% confidence
      interval {CI}: -0.035 to 0.145]), PDQ (beta=-9.013 [95% CI: -23.782 to 5.755]),
      or VAS-BP (beta=-0.849 [95% CI: -2.125 to 0.426]). These results suggest high
      satisfaction with the hospital experience may not necessarily correlate with
      favorable clinical outcomes. CONCLUSIONS: Top-box OHR was not associated with pre
      to 1-year postoperative improvement in EQ-5D, PDQ, and VAS-BP. Although the
      associations between high satisfaction and improvement in health status did not
      reach statistical significance, the best estimates from our multivariable models
      reflect greater clinical improvement with top-box satisfaction. Future studies
      should seek to investigate whether HCAHPS are a reliable indicator of quality
      care in lumbar spine surgery.

PMID- 28495243
TI  - Validation of topographic hybrid single-photon emission computerized tomography
      with computerized tomography scan in patients with and without nonspecific
      chronic low back pain. A prospective comparative study.
AB  - BACKGROUND CONTEXT: The evidence for the treatment for nonspecific chronic low
      back pain (ns CLBP) is very weak. Besides the complexity of the pain experience,
      a good biological marker or tool enabling identification of a pain generator is
      lacking. Hybrid imaging, combining single-photon emission computerized tomography
      (SPECT) with computerized tomography (CT) scan, has been proposed as useful in
      the diagnostic workup of patients with CLBP. PURPOSE: To evaluate the sensitivity
      of SPECT-CT in patients with ns CLBP (Group I) as compared with patients without
      CLBP (Group II). STUDY DESIGN: A prospective comparative study. PATIENT SAMPLE:
      Two hundred patients were enrolled: 96 in Group I and 104 in Group II. OUTCOME
      MEASURES: Only the physiological measurement of the incidence of hot spots was
      performed. The hot spots were rated as follows: 0=normal; 1=slightly colored (no
      hot spot on whole-body bone scan); and 2=clear hot spot (can be identified on the
      whole-body bone scan and confirmed on SPECT). To analyze the interobserver
      agreement when using this scoring system, a second independent reading was
      performed for 50 randomly chosen records. METHODS: Two hundred patients divided
      into two groups were referred to the department of Medical and Molecular Imaging
      for a topographic SPECT-CT. The first group consisted of patients with ns CLBP,
      diagnosed by a neurosurgeon. The control group consisted of patients referred for
      SPECT-CT for non-spinal conditions. Hot spots were assessed for all patients. A
      second independent reading, blinded for the results of the first reader, was
      performed on 25 randomly selected patients in each group. This study was
      investigator initiated, and no funding was received. None of the authors or their
      proxies have a potential conflict of interest. RESULTS: The odds of finding a
      normal image in the control group are 2.05 times higher than in Group I. The
      sensitivity score equals 2.37, meaning that the probability of detecting a hot
      spot (levels 1 or 2) is more than two times higher in Group I. When focusing on
      level 2 hot spots only, this score rises to 7.02, indicative of a high
      sensitivity. CONCLUSIONS: Single-photon emission computerized tomography with
      computerized tomography might have potential in the diagnostic workup of patients
      with ns CLBP, owing to its higher sensitivity when compared with other advanced
      medical imaging modalities.

PMID- 28495245
TI  - Massive parallel sequencing identifies RAPSN and PDHA1 mutations causing fetal
      akinesia deformation sequence.
AB  - INTRODUCTION: Fetal akinesia deformation sequence (FADS) or arthrogryposis
      multiplex congenita (AMC) is characterized by clinical ambiguity and genetic
      heterogeneity, hampering genetic diagnosis via traditional sequencing methods.
      Next generation sequencing (NGS) of all known disease-causing genes offers an
      elegant solution to identify the genetic etiology of AMC/FADS in a diagnostic
      setting. METHODS: An in-house developed disease-associated gene panel was
      conducted in two unrelated fetuses with FADS. First, a de novo analysis was
      performed on the entire disease-associated gene panel. If no pathogenic mutation
      was identified, analysis of variants retained in a specific subpanel with
      arthrogryposis/fetal akinesia-causing genes was performed. RESULTS: In the first
      family, FADS relates to a homozygous c.484G > A (p.Glu162Lys) mutation in the
      gene RAPSN. The second case concerns a sporadic patient with brain anomalies and
      arthrogryposis due to a de novo hemizygous c.498C > T splice-site mutation in the
      pyruvate dehydrogenase-alpha 1 (PDHA1) gene. DISCUSSION: NGS facilitated genetic
      diagnosis, and hence genetic counseling, for both families with AMC/FADS.
      Biallelic RAPSN mutations typically result in congenital myasthenia syndrome, or
      occasionally in FADS. This is the first report attributing the RAPSN mutation
      c.484G > A, identified in a homozygous state in patient 1, to FADS. The second
      patient represents the first case of AMC due to a PDHA1 mutation, advocating that
      pyruvate dehydrogenase deficiency should be considered in the differential
      diagnosis of fetal akinesia. This study illustrates the relevance of a disease
      associated-gene panel as a diagnostic tool in pregnancies complicated by this
      genetically heterogeneous condition.

PMID- 28495244
TI  - Rumen prokaryotic communities of ruminants under different feeding paradigms on
      the Qinghai-Tibetan Plateau.
AB  - Yak and Tibetan sheep are the major indigenous ruminants on the Qinghai-Tibetan
      Plateau in China. The aim of this work was to study the differences in ruminal
      fermentation parameters and rumen prokaryotic community composition between hosts
      and feeding paradigms. The 16S rRNA genes targeting bacteria and archaea were
      sequenced using the MiSeq platform. The results showed that the prokaryotic
      community structure between yak and Tibetan sheep was significantly different
      (P<0.01). A significant difference in structure was also found between groups of
      yaks barn fed with a total mixed ration (TMR) and those naturally grazing (NG)
      (P=0.034), as well as for Tibetan sheep of the two groups (P=0.026). The core
      prokaryotic populations that existed in the rumen mostly dominated the structure.
      There was an obvious correlation of the prokaryotic community composition at the
      phylum and genus levels with the host or the feeding pattern. In addition,
      Tibetan sheep showed significantly higher yields of volatile fatty acids (VFAs)
      than yak, as did the NG group compared with the TMR group. In conclusion, both
      the host and feeding pattern may influence rumen microbial ecology system, with
      host effects being more important than those of the feeding pattern.

PMID- 28495246
TI  - Clonidine adhesive patch for the treatment of tic disorders: A systematic review
      and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
      clonidine adhesive patch for tic disorders (TDs). METHODS: Medline, Embase,
      Cochrane central register of controlled trials and Chinese databases of CBM, CNKI
      were searched from inception to 08.2016 for randomized controlled studies (RCTs),
      open-label control studies of clonidine adhesive patch versus other medications
      or/and placebo for TDs. The cochrane Handbook for Systematic Reviews of
      Interventions was used to guide our study. RESULTS: Six studies involving 1145
      participants were included in this study. Among these studies, two study (N = 513
      patients) used placebo as a control and four studies (N = 632 patients) used
      positive drug controls. The results of meta-analysis suggested that clonidine
      adhesive patch may be as effective as haloperidol or tiapride for TDs. Adverse
      events (AEs) were reported in all studies, and the most common AEs of clonidine
      adhesive patch were rash (8.9%), lightheadedness (8.0%), dry mouth (4.0%). The
      AEs of clonidine adhesive patch were slight. CONCLUSION: These data provide
      moderate quality evidence that clonidine adhesive patch might be an effective and
      safe treatment option for TDs, and results from further trials are urgently
      needed to extend the evidence base.

PMID- 28495248
TI  - Clinical benefits, echocardiographic and MRI assessment after pulmonary
      sequestration treatment.
AB  - BACKGROUND: This study aimed to explore systematically procedural results,
      clinical benefits with echocardiographic and chest-MRI assessment of pulmonary
      sequestration percutaneous treatment. METHODS: 13 consecutive infants and
      children with diagnosis of isolated pulmonary sequestration (PS) had percutaneous
      closure of the aberrant artery supplying pulmonary sequestration between 2010 and
      2015. By protocol, echocardiographic and chest-MRI assessment was performed
      before and respectively at 6-12months and 1year with the aim to study the effects
      of embolization on heart volume overload and regression of pulmonary
      sequestration. RESULTS: Median age at diagnosis was 1year (95%CI 0-2.6); median
      age at treatment was 1.3years (95%CI1.01-2.85). In all pts the PS was confirmed
      by chest-MRI. Procedural success was 100%. After treatment, pts experiencing
      previously respiratory symptoms/infections remained asymptomatic at 2.9year
      follow-up. In pts with significant shunt due to PS, treatment resulted in
      amelioration in left or right cardiac chamber enlargement at 6 and 12month follow
      up. At distance from PS closure (median 14months), chest-MRI confirmed the
      closure of the aberrant artery and PS regression in 12 patients. In one case,
      despite the acute procedural success and the supplying artery remained closed,
      MRI detected residual PS revascularization. CONCLUSIONS: Percutaneous PS closure
      in infants and children is safe and provide regression in respiratory symptoms
      and heart chamber dilatation if significant shunt is present. MRI is able to
      define aberrant artery course and PS parenchima, and might represent a valid
      instrument to study residual PS parenchima during growth.

PMID- 28495247
TI  - Hospital variation in treatment and outcomes in acute coronary syndromes:
      Insights from the Alberta Contemporary Acute Coronary Syndrome Patients Invasive
      Treatment Strategies (COAPT) study.
AB  - BACKGROUND: We examined variation in hospital treatment and its relationship to
      clinical outcome in a large population-based cohort of ACS patients within a
      single payer-government funded health care system. METHODS: Patients hospitalized
      in 106 hospitals in Alberta, Canada with a primary diagnosis of ACS were included
      (July 1, 2010-March 31, 2013) with comparisons made across the three cardiac
      catheterization-capable hospitals (Sites A-C). Cox proportional-hazard regression
      models were used to examine the multivariable-adjusted association between site
      and 1-year death or repeat cardiovascular (CV) hospitalization (primary
      endpoint). RESULTS: Of 14,155 patients, 1938 (13.7%) were admitted to a community
      hospital without transfer to an invasive hospital (10.7% in-hospital death). The
      remaining were admitted (n=4514, 36.9%) or transferred (n=7703, 63.1%) to an
      invasive hospital (A:5480; B:3621; C:3116) where 11,247 (92.1%) underwent
      catheterization. Comorbidities and angiographic disease burden differed across
      sites. Variation in 30-day revascularization (PCI: 71.3%, 72.0%, 68.7%, p<0.001;
      CABG: 6.2%, 6.4%, 9.3%, p<0.001) and drug-eluting stent use for PCI (24.3%,
      54.6%, 50.5%, p<0.001) were observed. After adjustment for patient demographics
      and comorbidities, variation in rates of 1-year death or CV hospitalization was
      observed among those with 30-day revascularization (p(interaction)<0.001; B
      versus A: HR 0.78, 95%CI 0.66-0.91; C versus A: HR 0.77, 95%CI 0.65-0.91; B
      versus C: HR 1.01, 95%CI 0.84-1.21). CONCLUSIONS: Despite a government funded
      health system, we have shown variation in hospital treatment exists. Following
      adjustment hospital site was associated with differences in clinical outcome
      within 1year. Hence, further efforts may be warranted to help address potential
      disparities in ACS care.

PMID- 28495249
TI  - Heart rate variability to monitor performance in elite athletes: Criticalities
      and avoidable pitfalls.
AB  - BACKGROUND: Spectral analysis of Heart Rate Variability (HRV) is a simple, non
      invasive technique that is widely used in sport to assess sympatho-vagal
      regulation of the heart. Its employment is increasing partly due to the rising
      usage of wearable devices. However data acquisition using these devices may be
      suboptimal because they cannot discriminate between sinus and non-sinus beats and
      do not record any data regarding respiratory frequency. This information is
      mandatory for a correct clinical interpretation. METHODS: This study involved 974
      elite athletes, all of them underwent a complete autonomic assessment, by way of
      Autoregressive HRV analysis. RESULTS: In 91 subjects (9% of the total population)
      we observed criticalities of either cardiac rhythm or respiration. Through
      perusal of one-lead ECG analysis we observed that 77 subjects had atrial or
      ventricular ectopy, i.e. conditions which impair stationarity and sinus rhythm.
      Running anyway autonomic nervous system analysis in this population, we observed
      that RR variance and raw values of LF and HF regions are significantly higher in
      arrhythmic subjects. In addition 14 subjects had slow (about 6 breath/min, 0.1Hz)
      respiration. This condition clouds the separation between LF from HF spectral
      regions of RR interval variability, respectively markers of the prevalent
      sympathetic and vagal modulation of SA node and of their synergistic interaction.
      CONCLUSIONS: Caution must be payed when assessing HRV with non-ECG wearable
      devices. Recording ECG signal and ensuring that respiratory rate is higher than
      10 breath/min are both prerequisites for a more reliable analysis of HRV
      particularly in athletes.

PMID- 28495250
TI  - Austerity and its implications for immigrant health in France.
AB  - The ongoing economic crisis in France increasingly has affected immigrant rights,
      including access to health care. Consistent with a 2014 League Against Cancer
      survey, we identify the ways in which sickness produces a "double penalty" for
      immigrants with serious illness. Immigrants with chronic illnesses such as
      cancer, diabetes, and other debilitating conditions divert vital funds from daily
      needs to deal with sickness and loss of work while at the same time national
      austerity measures shred the state's traditional safety net of social services
      and support. We examine how immigrants strategize to manage financial exigencies,
      therapeutic itineraries and social relations in the face of these converging
      pressures. We base our findings on two studies related by this theme: an
      investigation of health inequalities in the Medoc region, in which 88 women, 44
      of North African and Eastern European origin, were interviewed over a three-year
      period (2010-2013); and a three-year study (2014-2017) of West African immigrant
      women with breast cancer seeking treatment in the greater Paris region, 70
      members of immigrant associations, and clinical personnel in three hospitals.

PMID- 28495251
TI  - Vector control: time for a planetary health approach.

PMID- 28495252
TI  - Smoking status and HIV in low-income and middle-income countries.

PMID- 28495253
TI  - Every breath you take....

PMID- 28495254
TI  - Maternal hepatitis B virus infection and risk of preterm birth in China.

PMID- 28495255
TI  - Women leaders in global health.

PMID- 28495256
TI  - Research capacity building-obligations for global health partners.

PMID- 28495257
TI  - The Lancet Global Health Commission on High Quality Health Systems-where's the
      complexity?

PMID- 28495258
TI  - The Lancet Global Health Commission on High Quality Health Systems-where's the
      complexity? - Authors' reply.

PMID- 28495259
TI  - Unreliable estimation of prevalence of fetal alcohol syndrome.

PMID- 28495260
TI  - Unreliable estimation of prevalence of fetal alcohol syndrome.

PMID- 28495261
TI  - Unreliable estimation of prevalence of fetal alcohol syndrome - Authors' reply.

PMID- 28495262
TI  - Access to Chagas disease treatment in non-endemic countries: the case of Spain.

PMID- 28495263
TI  - Tobacco use among people living with HIV: analysis of data from Demographic and
      Health Surveys from 28 low-income and middle-income countries.
AB  - BACKGROUND: Tobacco use among people living with HIV results in excess morbidity
      and mortality. However, very little is known about the extent of tobacco use
      among people living with HIV in low-income and middle-income countries (LMICs).
      We assessed the prevalence of tobacco use among people living with HIV in LMICs.
      METHODS: We used Demographic and Health Survey data collected between 2003 and
      2014 from 28 LMICs where both tobacco use and HIV test data were made publicly
      available. We estimated the country-specific, regional, and overall prevalence of
      current tobacco use (smoked, smokeless, and any tobacco use) among 6729 HIV
      positive men from 27 LMICs (aged 15-59 years) and 11 495 HIV-positive women from
      28 LMICs (aged 15-49 years), and compared them with those in 193 763 HIV-negative
      men and 222 808 HIV-negative women, respectively. We estimated prevalence
      separately for males and females as a proportion, and the analysis accounted for
      sampling weights, clustering, and stratification in the sampling design. We
      computed pooled regional and overall prevalence estimates through meta-analysis
      with the application of a random-effects model. We computed country, regional,
      and overall relative prevalence ratios for tobacco smoking, smokeless tobacco
      use, and any tobacco use separately for males and females to study differences in
      prevalence rates between HIV-positive and HIV-negative individuals. FINDINGS: The
      overall prevalence among HIV-positive men was 24.4% (95% CI 21.1-27.8) for
      tobacco smoking, 3.4% (1.8-5.6) for smokeless tobacco use, and 27.1% (22.8-31.7)
      for any tobacco use. We found a higher prevalence in HIV-positive men of any
      tobacco use (risk ratio [RR] 1.41 [95% CI 1.26-1.57]) and tobacco smoking (1.46
      [1.30-1.65]) than in HIV-negative men (both p<0.0001). The difference in
      smokeless tobacco use prevalence between HIV-positive and HIV-negative men was
      not significant (1.26 [1.00-1.58]; p=0.050). The overall prevalence among HIV
      positive women was 1.3% (95% CI 0.8-1.9) for tobacco smoking, 2.1% (1.1-3.4) for
      smokeless tobacco use, and 3.6% (95% CI 2.3-5.2) for any tobacco use. We found a
      higher prevalence in HIV-positive women of any tobacco use (RR 1.36 [95% CI 1.10
      1.69]; p=0.0050), tobacco smoking (1.90 [1.38-2.62]; p<0.0001), and smokeless
      tobacco use (1.32 [1.03-1.69]; p=0.030) than in HIV-negative women.
      INTERPRETATION: The high prevalence of tobacco use in people living with HIV in
      LMICs mandates targeted policy, practice, and research action to promote tobacco
      cessation and to improve the health outcomes in this population. FUNDING: South
      African Medical Research Council and the UK Medical Research Council.

PMID- 28495264
TI  - Community engagement and integrated health and polio immunisation campaigns in
      conflict-affected areas of Pakistan: a cluster randomised controlled trial.
AB  - BACKGROUND: Pakistan faces huge challenges in eradicating polio due to widespread
      poliovirus transmission and security challenges. Innovative interventions are
      urgently needed to strengthen community buy-in, to increase the coverage of oral
      polio vaccine (OPV) and other routine immunisations, and to enhance immunity
      through the introduction of inactivated polio vaccine (IPV) in combination with
      OPV. We aimed to evaluate the acceptability and effect on immunisation coverage
      of an integrated strategy for community engagement and maternal and child health
      immunisation campaigns in insecure and conflict-affected polio-endemic districts
      of Pakistan. METHODS: We did a community-based three-arm cluster randomised trial
      in healthy children aged 1 month to 5 years that resided within the study sites
      in three districts of Pakistan at high risk of polio. Clusters were randomly
      assigned by a computer algorithm using restricted randomisation in blocks of 20
      by an external statistician (1:1:1) to receive routine polio programme activities
      (control, arm A), additional interventions with community outreach and
      mobilisation using an enhanced communication package and provision of short-term
      preventive maternal and child health services and routine immunisation (health
      camps), including OPV (arm B), or all interventions of arm B with additional
      provision of IPV delivered at the maternal and child health camps (arm C). An
      independent team conducted surveys at baseline, endline, and after each round of
      supplementary immunisation activity for acceptability and effect. The primary
      outcome measures for the study were coverage of OPV, IPV, and routine extended
      programme on immunisation vaccines and changes in the proportion of unvaccinated
      and fully vaccinated children. This trial is registered with ClinicalTrials.gov,
      number NCT01908114. FINDINGS: Between June 4, 2013, and May 31, 2014, 387
      clusters were randomised (131 to arm A, 127 to arm B, and 129 to arm C). At
      baseline, 28 760 children younger than 5 years were recorded in arm A, 30 098 in
      arm B, and 29 126 in arm C. 359 clusters remained in the trial until the end (116
      in arm A, 120 in arm B, and 123 in arm C; with 23 334 children younger than 5
      years in arm A, 26 110 in arm B, and 25 745 in arm C). The estimated OPV coverage
      was 75% in arm A compared with 82% in arm B (difference vs arm A 6.6%; 95% CI 4.8
      8.3) and 84% in arm C (8.5%, 6.8-10.1; overall p<0.0001). The mean proportion of
      routine vaccine doses received by children younger than 24 months of age was 43%
      in arm A, 52% in arm B (9%, 7-11) and 54% in arm C (11%, 9-13; overall p<0.0001).
      No serious adverse events requiring hospitalisation were reported after
      immunisation. INTERPRETATION: Despite the challenges associated with the polio
      end-game in high-risk, conflict-affected areas of Pakistan, a strategy of
      community mobilisation and targeted community-based health and immunisation camps
      during polio immunisation campaigns was successful in increasing vaccine
      coverage, including polio vaccine coverage. FUNDING: Bill & Melinda Gates
      Foundation.

PMID- 28495265
TI  - Continuous positive airway pressure for children with undifferentiated
      respiratory distress in Ghana: an open-label, cluster, crossover trial.
AB  - BACKGROUND: In low-income and middle-income countries, invasive mechanical
      ventilation is often not available for children at risk of death from respiratory
      failure. We aimed to determine if continuous positive airway pressure (CPAP), a
      form of non-invasive ventilation, decreases all-cause mortality in children with
      undifferentiated respiratory distress in Ghana. METHODS: This open-label,
      cluster, crossover trial was done in two Ghanaian non-tertiary hospitals where
      invasive mechanical ventilation is not routinely available. Eligible participants
      were children aged from 1 month to 5 years with a respiratory rate of more than
      50 breaths per min in children 1-12 months old, or more than 40 breaths per min
      in children older than 12 months, and use of accessory muscles or nasal flaring.
      CPAP machines were allocated to one hospital during each study block, while the
      other hospital served as the control site. The initial intervention site was
      randomly chosen using a coin toss. 5 cm of water pressure was delivered via CPAP
      nasal prongs. The primary outcome measure was all-cause mortality rate at 2 weeks
      after enrolment in patients for whom data were available after 2 weeks. We also
      did post-hoc regression analysis and subgroup analysis of children by malaria
      status, oxygen saturation, and age. This study is registered with
      ClinicalTrials.gov, number NCT01839474. FINDINGS: Between Jan 20, 2014, and Dec
      5, 2015, 2200 children were enrolled: 1025 at the intervention site and 1175 at
      the control site. Final analysis included 1021 patients in the CPAP group and
      1160 patients in the control group. 2 weeks after enrolment, 26 (3%) of 1021
      patients in the CPAP group, and 44 (4%) of 1160 patients in the control group,
      had died (relative risk [RR] of mortality 0.67, 95% CI 0.42-1.08; p=0.11). In
      children younger than 1 year, all-cause mortality was ten (3%) of 374 patients in
      the CPAP group, and 24 (7%) of 359 patients in the control group (RR 0.40, 0.19
      0.82; p=0.01). After adjustment for study site, time, and clinically important
      variables, the odds ratio for 2-week mortality in the CPAP group versus the
      control group was 0.4 in children aged up to 6 months, 0.5 for children aged 12
      months, 0.7 for children aged 24 months, and 1.0 for those aged 36 months. 28
      patients (3%) in the CPAP group and 24 patients (2%) in the control group had
      CPAP-related adverse events, such as vomiting, aspiration, and nasal, skin, or
      eye trauma. No serious adverse events were observed. INTERPRETATION: In the
      unadjusted analysis the use of CPAP did not decrease all-cause 2-week mortality
      in children 1 month to 5 years of age with undifferentiated respiratory distress.
      After adjustment for study site, time, and clinically important variables, 2-week
      mortality in the CPAP group versus the control group was significantly decreased
      in children 1 year of age and younger. CPAP is safe and improves respiratory rate
      in a non-tertiary setting in a lower-middle-income country. FUNDING: General
      Electric Foundation.

PMID- 28495266
TI  - Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm
      birth: a population-based cohort study.
AB  - BACKGROUND: Preterm birth is the leading cause of child death in children younger
      than 5 years. Large cohort studies in developed countries have shown that
      maternal hepatitis B virus infection is associated with preterm birth, but there
      is little reliable evidence from China and other developing countries, where
      hepatitis B virus prevalence is intermediate or high. Hence, we designed this
      study to investigate the association between pre-pregnancy hepatitis B virus
      infection and risk of preterm and early preterm birth. METHODS: Between Jan 1,
      2010, and Dec 31, 2012, we did a population-based cohort study using data from
      489 965 rural women aged 21-49 years who had singleton livebirths from 220
      counties of China who participated in the National Free Preconception Health
      Examination Project. Participants were divided into three groups according to
      their pre-pregnancy status of hepatitis B virus infection: women uninfected with
      hepatitis B virus (control group), women who were HBsAg positive and HBeAg
      negative (exposure group 1), and women who were both HBsAg and HBeAg positive
      (exposure group 2). The primary outcome was preterm birth (gestation at less than
      37 weeks). We used log-binomial regression to estimate adjusted risk ratios (aRR)
      of preterm birth for women with pre-pregnancy hepatitis B virus infection, and
      risk of early preterm birth (gestation less than 34 weeks). FINDINGS: 489 965
      women met inclusion criteria and were included in this study; of these, 20 827
      (4.3%) were infected with hepatitis B virus. Compared with women who were not
      infected with hepatitis B virus, women who were HBsAg positive and HBeAg negative
      had a 26% higher risk of preterm birth (aRR 1.26, 95% CI 1.18-1.34) and women who
      were both HBsAg and HBeAg positive had a 20% higher risk of preterm birth (aRR
      1.20, 1.08-1.32). Compared with women who were not infected with hepatitis B
      virus, women who were HBsAg positive and HBeAg negative manifested an 18% higher
      risk of early preterm birth (gestation less than 34 weeks; aRR 1.18, 1.04-1.34)
      and women who were both HBsAg and HBeAg positive had a 34% higher risk of early
      preterm birth (aRR 1.34, 1.10-1.61). Maternal pre-pregnancy hepatitis B virus
      infection was independently associated with higher risk of preterm birth and
      early preterm birth. These associations were similar in subgroups of participants
      as defined by baseline characteristics. INTERPRETATION: Besides mother-to-child
      transmission, the risk of preterm birth in women infected with hepatitis B virus
      should not be neglected. Comprehensive programmes that focus on early detection
      of hepatitis B virus infection before pregnancy and provide appropriate medical
      intervention for women infected with hepatitis B virus before and during
      pregnancy would be helpful in improving maternal and neonatal outcomes and
      reducing child mortality. FUNDING: Chinese Association of Maternal and Child
      Health Studies.

PMID- 28495267
TI  - The Evolutionary Interplay between Adaptation and Self-Fertilization.
AB  - Genome-wide surveys of nucleotide polymorphisms, obtained from next-generation
      sequencing, have uncovered numerous examples of adaptation in self-fertilizing
      organisms, especially regarding changes to climate, geography, and reproductive
      systems. Yet existing models for inferring attributes of adaptive mutations often
      assume idealized outcrossing populations, which risks mischaracterizing
      properties of these variants. Recent theoretical work is emphasizing how various
      aspects of self-fertilization affects adaptation, yet empirical data on these
      properties are lacking. We review theoretical and empirical studies demonstrating
      how self-fertilization alters the process of adaptation, illustrated using
      examples from current sequencing projects. We propose ideas for how future
      research can more accurately quantify aspects of adaptation in self-fertilizers,
      including incorporating the effects of standing variation, demographic history,
      and polygenic adaptation.

PMID- 28495268
TI  - The presence of VEGF and Notch2 during preantral-antral follicular transition in
      infantile rats: Anatomical evidence and its implications.
AB  - Folliculogenesis is a process that depends on angiogenesis, in which VEGF and
      Notch signaling pathway members are involved. Although this pathway is present in
      preantral and antral follicular structures during the second stage of
      folliculogenesis, this association has not been described. Therefore, this study
      aimed to identify VEGF and Notch2 in ovary structures of infantile rats after
      induction of follicular development with a gonadotropin stimulus. In order to
      explore this possibility we analyzed rat ovary morphology from days 10-25 after
      birth; subsequently, the transition from preantral follicle to an antral stage
      was analyzed by the induction of follicular development with equine chorionic
      gonadotropin (eCG) and VEGF and Notch were identified in the rat ovary by
      fluorescence. The histological analysis revealed that the ovary of a 10-day-old
      rat has the highest percentage of preantral follicles and based on this a 10IU
      eCG dose promoted an increase in the number of antral follicles, as well as a
      decrease in the number of preantral follicles, related to which there was an
      increase in ovary weight and size. In addition, a higher concentration of
      circulating estradiol was observed, proliferation of granulosa cells in both
      follicle groups was stimulated, and the accumulation of VEGF in granulosa and
      theca cells and in the antral follicle oocyte was increased (p<0.05), whereas the
      presence of Notch2 was limited to mural granulosa cells, in granulosa cells that
      formed the cumulus oophorus and in the oocyte of both groups of follicles. The
      multiple correspondence analysis allowed us to support an association between
      VEGF and Notch2 during the transition from preantral to antral follicles in the
      ovary of an infantile rat.

PMID- 28495269
TI  - Identification of novel regulatory GRE-binding elements in the porcine IP3R1 gene
      promoter and their transcriptional activation under glucocorticoid stimulation.
AB  - Inositol 1,4,5-trisphosphate receptor 1 (IP3R1) is a type of ligand-gated calcium
      channel that is expressed predominantly in mammalian skeletal muscle, where it
      acts as a key regulator of calcium homeostasis. In meat, calcium disequilibrium
      is accompanied by the deterioration of meat quality. Here we show that serum
      cortisol concentration was higher and the IP3R1 gene expression level increased
      markedly in pigs exposed to high stress. In porcine primary muscle cells,
      dexamethasone (DEX, a synthetic glucocorticoid) increased the protein levels of
      porcine IP3R1 and GRalpha, and cell apoptosis, and the specific GRalpha inhibitor
      RU486 attenuated these effects. DEX also increased the expression of IP3R1 at
      both the gene and protein levels, and this expression was attenuated by RU486,
      siRNA against GRalpha, and the transcriptional inhibitor actinomycin D. DEX
      significantly reduced cell viability and increased the intracellular calcium
      concentration, and these effects were attenuated by siRNA against GRalpha.
      Bioinformatics analyses predicted a potential glucocorticoid response element
      (GRE) located in the region -326 to -309 upstream of the IP3R1 promoter and
      highly conserved in pigs and other mammalian species. Promoter analysis showed
      that this region containing the GRE was critical for transcriptional activity of
      porcine IP3R1 under DEX stimulation. This was confirmed by deletion and site
      mutation methods. EMSA and ChIP assays showed that this potential GRE bound
      specifically to GRalpha and this complex activated the transcription of the IP3R1
      gene. Taken together, these data suggest that DEX-mediated induction of IP3R1
      influences porcine muscle cells through the transcriptional activation of a
      mechanism involving interactions between GRalpha and a GRE present in the
      proximal IP3R1 promoter. This process can lead to an imbalance in intracellular
      calcium concentration, which may subsequently activate the apoptosis signal and
      decrease cell activity, and cause deterioration of meat quality.

PMID- 28495270
TI  - Egg deposition of maternal testosterone is primarily controlled by the
      preovulatory peak of luteinizing hormone in Japanese quail.
AB  - Differential transfer of maternal testosterone (T) into egg yolk provides a means
      of adjusting an offspring's phenotype to ambient environmental conditions. While
      the environmental and genetic driven variability in yolk T levels is widely
      described, the underlying mechanisms are poorly understood. Here, we investigated
      whether neuroendocrine mechanisms controlling ovulatory processes are associated
      with the regulation of yolk T deposition. Circulatory profiles of luteinizing
      hormone (LH), T and estradiol levels were analysed during the last 7h before
      ovulation in Japanese quail selected for contrasting yolk T concentrations.
      Moreover, the pituitary responsiveness to a single challenge with gonadotropin
      releasing hormone (GnRH) was evaluated. High egg T (HET) birds displayed higher
      concentrations of LH at 3.5h before ovulation than low egg T (LET) birds while no
      differences were found around the time of expected ovulation. The pre-ovulatory
      profile of T and estradiol levels did not differ between LET and HET females but
      pre-ovulatory plasma T positively correlated with LH concentrations at 6.5h and
      3.5h before ovulation. The LH response to GnRH did not differ between LET and HET
      females. Our results demonstrate that the pre-ovulatory LH surge can determine
      the amount of T transferred into the egg yolk. This link between yolk T
      deposition and the ovulatory cycle driven variation of reproductive hormones may
      explain balance between the effects of circulating T on female's reproductive
      physiology and yolk T on offspring phenotype.

PMID- 28495271
TI  - The melanocortin-2 receptor of the rainbow trout: Identifying a role for critical
      positions in transmembrane domain 4, extracellular loop 2, and transmembrane
      domain 5 in the activation of rainbow trout MC2R.
AB  - The activation of either teleost or tetrapod melanocortin-2 receptor (MC2R)
      orthologs requires interaction between the HFRW motif and R/KKRRP motif in the
      primary sequence of ACTH, and two corresponding sites on the melanocortin 2
      receptor. While the HFRW contact site on MC2R appears to involve residues in TM2,
      TM3, and TM6, several studies on human MC2R point to the EC2/TM5 region of MC2R
      as a possible location for the R/KKRRP contact site. In this study nineteen
      single-alanine mutants of rainbow trout (rt) MC2R were made beginning at V153 in
      TM4, at all positions in EC2 (extracellular loop 2), to F175 in TM5. For twelve
      of these alanine mutants (i.e., V153, G155, C162, D163, T165, V166, I167, H169,
      F170, H172, V173, L174), alanine substitution did not have a statistically
      significant effect on activation of the receptor. For four of these alanine
      mutations (i.e., V157, M158, F161, K168), while the negative shift in ligand
      sensitivity was statistically significant, the magnitude of the negative shift in
      activation was fivefold or less. However, for substitution at V159 in TM4
      (negative shift in activation: 110 fold), F171 in TM5 (negative shift in
      activation: 48-fold), and F175 in TM5 (negative shift in activation: 100 fold),
      the effect on activation was both statistically significant and may be
      physiologically relevant. To support this conclusion, a triple alanine mutant of
      rtMC2R (V159/A, F171/A, F175/A), and this mutant receptor could not be activated
      by ACTH at concentrations as high as 10-6M. A Cell Surface ELISA analysis
      indicated that the trafficking of the triple alanine mutant rtMC2R to the plasma
      membrane was not impaired by the alanine substitutions. Collectively, these
      observations point to a critical role for TM4 and TM5 in the activation of the
      rainbow trout melanocortin-2 receptor.

PMID- 28495272
TI  - Pannexins in vision, hearing, olfaction and taste.
AB  - In mammals, the pannexin gene family consists of three members (Panx1, 2, 3),
      which represent a class of integral membrane channel proteins sharing some
      structural features with chordate gap junction proteins, the connexins. Since
      their discovery in the early 21st century, pannexin expression has been detected
      throughout the vertebrate body including eye, ear, nose and tongue, making the
      investigation of the roles of this new class of channel protein in health and
      disease very appealing. The localization in sensory organs, coupled with unique
      channel properties and associations with major signaling pathways make Panx1, and
      its relative's, significant contributors for fundamental functions in sensory
      perception. Until recently, cell-based studies were at the forefront of pannexin
      research. Lately, the availability of mice with genetic ablation of pannexins
      opened new avenues for testing pannexin functions and behavioural phenotyping.
      Although we are only at the beginning of understanding the roles of pannexins in
      health and disease, this review summarizes recent advances in elucidating the
      various emerging roles pannexins play in sensory systems, with an emphasis on
      unresolved conflicts.

PMID- 28495273
TI  - The Key of the Maze: The role of mental imagery and cognitive flexibility in
      navigational planning.
AB  - Spatial navigation planning ability relies on both mental imagery and cognitive
      flexibility. Considering the importance of planning ability in everyday life,
      several neuropsychological tests are used in clinical practice for its
      assessment, although some of these are not aimed at assessing the strategies of
      navigational planning. The Porteus Maze Test (PMT) and the Key Search Task (KST)
      require to plan a strategy in a maze and in an imagined space, respectively. To
      the best of our knowledge, although these two tests share some features, the
      relationship between them has never been explored. The purpose of the present
      study was to investigate, for the first time, the relationship between the PMT
      and the KST performances in 38 healthy subjects in order to understand the
      implications of this association for the assessment of spatial navigation
      ability. Subjects were subdivided in bad or good navigation planners on the basis
      of the their KST score. The results of the study have revealed a significant
      difference (t=2.35; p=0.03) in the number of errors made at the PMT by bad
      navigational planners (0.78+/-0.28) and good navigational planners (0.10+/-0.06).
      The first group (bad navigational planners) made more errors at the PMT than the
      good navigational planners (who made less errors at the PMT). This provides
      evidence of the possibility to use the KST and the PMT in a combined way as a new
      tool for the assessment of spatial navigational planning ability. Furthermore,
      this finding highlights the importance of mental imagery and cognitive
      flexibility in spatial navigation, suggesting that these functions could be the
      link between a good planning ability and a successful spatial navigation. In
      conclusion, this study suggests that an efficient navigation would not be
      possible without a good navigational planning ability.

PMID- 28495274
TI  - Females are sensitive to unpleasant human emotions regardless of the emotional
      context of photographs.
AB  - Previous studies have demonstrated that females exhibit higher sensitivity than
      males to the emotional state of a person in a photograph. The present study
      examined whether such females' sensitivity to human emotions could be observed
      even when the background emotional contexts were incongruent with facial
      expressions. The late positive potential (LPP) was measured while 19-female and
      15-male participants viewed a photograph of a face with varied emotional
      expressions (pleasant, neutral, or unpleasant) superimposed on a background
      photograph with varied valences (pleasant, neutral, or unpleasant). The results
      showed that unpleasant background photographs elicited a larger LPP compared to
      pleasant and neutral background photographs in both female and male participants.
      In contrast, a larger LPP for the unpleasant face photographs was observed only
      in female participants. Furthermore, the effect of face photographs did not
      interact with the effect of background photographs. These results suggest that
      females are sensitive to human emotions regardless of the emotional context.

PMID- 28495275
TI  - Cancer risk paradox: grand plans fall short?

PMID- 28495276
TI  - Immune checkpoint inhibitors in malignant pleural mesothelioma.

PMID- 28495277
TI  - Poorly specified fasting conditions in clinical research could lead to treatment
      failure.

PMID- 28495278
TI  - Engaging specialist oncologists in the assessment of oncology drugs in Canada.

PMID- 28495279
TI  - Beauties of the Night.

PMID- 28495280
TI  - Sentinel-lymph-node mapping in endometrial cancer.

PMID- 28495281
TI  - Sentinel-lymph-node mapping in endometrial cancer.

PMID- 28495282
TI  - Sentinel-lymph-node mapping in endometrial cancer - Authors' reply.

PMID- 28495283
TI  - Molecular diagnoses of century-old childhood tumours.

PMID- 28495284
TI  - Genomic biomarkers for precision radiation medicine.

PMID- 28495285
TI  - Genomic biomarkers for precision radiation medicine - Authors' reply.

PMID- 28495286
TI  - Widening the gap: additional concerns with crowdfunding in health care.

PMID- 28495287
TI  - Peri-operative chemotherapy with or without bevacizumab in operable
      oesophagogastric adenocarcinoma.

PMID- 28495288
TI  - Peri-operative chemotherapy with or without bevacizumab in operable
      oesophagogastric adenocarcinoma.

PMID- 28495289
TI  - Peri-operative chemotherapy with or without bevacizumab in operable
      oesophagogastric adenocarcinoma - Authors' reply.

PMID- 28495290
TI  - Correction to Lancet Oncol 2017; 18: e186.

PMID- 28495291
TI  - Mid-face bone destruction involving the palate.

PMID- 28495292
TI  - The living organism: Strengthening the basis.
AB  - In spite of the considerable amount of literature dedicated to the living
      organism, it retains its mysteries. One of the most discussed aspects nowadays is
      whether the term "cognition" can be attributed to all classes of organisms, or
      whether it only refers to a metaphoric use of one human reality. Our approach
      consists of retaining the term "cognition" and making it a technical term, in
      order to propose a generic model. In this way, cognition becomes what finally
      characterises an organism as an autonomous agent. This perspective eliminates
      some misplaced questions, and helps to reframe old ones. The cognitive dimension
      can be apprehended indirectly only through its appearances. These direct us
      towards a modular model of cognition and orientate research towards the
      clarification of specific modules for each class of organisms.

PMID- 28495293
TI  - [How to organize hospital discharge after COPD exacerbation?]

PMID- 28495294
TI  - [Which inhaled pharmacological treatment during acute COPD exacerbation in
      community-based practice?]

PMID- 28495295
TI  - [Guidelines to integrate palliative management in patients with acute COPD
      exacerbation].

PMID- 28495297
TI  - [Non-pharmacological management in acute COPD exacerbations].

PMID- 28495296
TI  - [Non-pharmacological management of acute COPD exacerbations in community-based
      practice].

PMID- 28495298
TI  - [Antibiotics during acute COPD exacerbations].

PMID- 28495299
TI  - A randomized comparison of a novel nitinol-frame low-dose-copper intrauterine
      contraceptive and a copper T380S intrauterine contraceptive.
AB  - OBJECTIVE: We sought to compare VeraCept (VC175), a novel nitinol intrauterine
      contraceptive (IUC) with 175 square-mm of copper surface area, to a copper T380S
      IUC. STUDY DESIGN: We enrolled parous women into a randomized subject-blinded
      comparison of VC175 and a copper T380S in a 2:1 fashion at a single clinic. The
      primary outcomes were total adverse events and continuation at 12 months. We also
      examined pain on insertion, ease of placement, expulsion, tolerability and
      pregnancy. Subjective ratings were on a 5-point Likert scale (0, no pain to 5,
      worst pain). We followed subjects through 24-month follow-up. RESULTS: We
      enrolled 300 women with 199 randomized to VC175 and 101 to the T380S. Insertion
      was successful in 198 subjects for VC175 and 100 for the T380S. Mean age was 25
      years (range 18, 41), and median parity was 2 (range 1, 8), with 39% having only
      had Cesarean deliveries. No subjects developed clinical infection or reported
      serious adverse events. In the VC175 and T380S groups, mean pain at insertion was
      1.4 and 2.4, respectively (p<.01). At the 12-month primary endpoint for VC175 and
      T380S, respectively, continuation was 84% and 68% (p<.002) with expulsions in
      5.0% and 12.0% (p<.05) and removal for pain/bleeding in 3.5% and 17.0% (p<.01).
      At the 24-month visit for VC175 and T380S, respectively, continuation was 77% and
      62% (p<.02 by log-rank). One ectopic pregnancy was identified at the 12-month
      follow-up in a VC175 user. No other pregnancies were diagnosed. With 297.3 and
      132.4 woman-years, pregnancy rates were 0.3 and 0.0 per 100 woman-years for VC175
      and T380S, respectively. CONCLUSIONS: VC175 resulted in less pain at insertion,
      fewer expulsions and higher total continuation than the T380S, with similar
      contraceptive efficacy. IMPLICATIONS: VC175 is a promising new intrauterine
      copper contraceptive on a nitinol frame that warrants further clinical trials.

PMID- 28495300
TI  - Aortic Valve Stenosis Increases Helical Flow and Flow Complexity: A Study of
      Intra-Operative Cardiac Vector Flow Imaging.
AB  - Aortic valve stenosis alters blood flow in the ascending aorta. Using intra
      operative vector flow imaging on the ascending aorta, secondary helical flow
      during peak systole and diastole, as well as flow complexity of primary flow
      during systole, were investigated in patients with normal, stenotic and replaced
      aortic valves. Peak systolic helical flow, diastolic helical flow and flow
      complexity during systole differed between the groups (p < 0.0001), and
      correlated to peak systolic velocity (R = 0.94, 0.87 and 0.88, respectively). The
      study indicates that aortic valve stenosis increases helical flow and flow
      complexity, which are measurable with vector flow imaging. For assessment of
      aortic stenosis and optimization of valve surgery, vector flow imaging may be
      useful.

PMID- 28495301
TI  - 2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac
      monitoring/telemetry.
AB  - Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts
      to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily
      obtained from the standard ECG. Accurate and timely characterization of
      arrhythmias is crucial to direct therapies that can have an important impact on
      diagnosis, prognosis or patient symptom status. The rhythm information derived
      from the large variety of AECG recording systems can often lead to appropriate
      and patient-specific medical and interventional management. The details in this
      document provide background and framework from which to apply AECG techniques in
      clinical practice, as well as clinical research.

PMID- 28495302
TI  - Optically stimulated luminescence of natural NaCl mineral from Dead Sea exposed
      to gamma radiation.
AB  - In this work, the continuous wave - optically stimulated luminescence (CW-OSL)
      emissions of natural salt minerals, collected from Dead Sea in summer of 2015,
      were studied. The CW-OSL dose response of natural salt showed a linear range
      between 0.5Gy and 10Gy of gamma radiation of 60Co. Samples exposed at 3Gy
      exhibited good repeatability with a variation coefficient of 4.6%. The CW-OSL
      response as function of the preheating temperature (50-250 degrees C) was
      analyzed. An increase of 15% of the CW-OSL response was observed in NaCl samples
      during storage period of 336h. The results showed that the natural Dead Sea salt
      minerals could be applied as natural dosimeter of gamma radiation.

PMID- 28495303
TI  - The characteristics of salivary pepsin in patients with severe motor and
      intellectual disabilities.
AB  - PURPOSE: The aim of the present study was to determine the utility of measuring
      the salivary pepsin level (SPL) as an objective assessment of gastroesophageal
      reflux disease (GERD) in severe motor and intellectual disabilities (SMID)
      patients. SUBJECTS AND METHODS: This prospective study included 26 SMID patients
      who underwent simultaneous 24-h multichannel intraluminal impedance pH
      measurement (pH/MII) and SPL evaluation. The enrolled patients were divided into
      GERD (+) or GERD (-) groups according to the pH/MII findings. The age, gender and
      pH/MII parameters were compared between the two groups. A correlation analysis
      was also conducted for the SPL following early-morning fasting and post-enteral
      feeding and the age, gender, presence of gastrostomy and tracheostomy and pH/MII
      parameters. The SPL was compared between the two sampling groups. RESULTS:
      Fifteen patients were classified as GERD (+), and 11 patients were classified as
      GERD (-). The mean SPL following early-morning fasting and post-enteral feeding
      among all patients were 104.3 (median: 38, 25th and 75th percentile: 12, 361)
      ng/ml and 222.2 (median: 152:0, 500) ng/ml, respectively. Regarding positivity,
      76.9% and 73.1% of SPL values in early-morning fasting and post-enteral feeding
      SMID patients, respectively, were positive (?16ng/ml). The SPL following early
      morning fasting demonstrated a weak but significant positive correlation with
      age. In contrast, we noted no correlation between the pH/MII parameters and the
      SPL for either the early-morning fasting or post-enteral feeding patients, and no
      significant difference in the SPL was observed between the GERD (+) and (-)
      patients. CONCLUSIONS: The present study showed that a high proportion of SMID
      patients had a relatively high SPL, regardless of the presence of GERD. The SPL
      in SMID patients might be affected by several distinctive factors in addition to
      gastroesophageal reflux.

PMID- 28495304
TI  - [Large cervicodorsal epidural abscess].

PMID- 28495305
TI  - Mechanism for optimization of signal-to-noise ratio of dopamine release based on
      short-term bidirectional plasticity.
AB  - Repeated electrical stimulation of dopamine (dopamine) fibers can cause variable
      effects on further dopamine release; sometimes there are short-term decreases
      while in other cases short-term increases have been reported. Previous studies
      have failed to discover what factors determine in which way dopamine neurons will
      respond to repeated stimulation. The aim of the present study was therefore to
      investigate what determines the direction and magnitude of this particular form
      of short-term plasticity. Fixed potential amperometry was used to measure
      dopamine release in the nucleus accumbens in response to two trains of electrical
      pulses administered to the ventral tegmental area of anesthetized mice. When the
      pulse trains were of equal magnitude we found that low magnitude stimulation was
      associated with short-term suppression and high magnitude stimulation with short
      term facilitation of dopamine release. Secondly, we found that the magnitude of
      the second pulse train was critical for determining the sign of the plasticity
      (suppression or facilitation), while the magnitude of the first pulse train
      determined the extent to which the response to the second train was suppressed or
      facilitated. This form of bidirectional plasticity might provide a mechanism to
      enhance signal-to-noise ratio of dopamine neurotransmission.

PMID- 28495306
TI  - Long-term effects of enriched environment following neonatal hypoxia-ischemia on
      behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined
      treatment with G-CSF.
AB  - Increasing evidence shows that exposure to an enriched environment (EE) is
      neuroprotective in adult and neonatal animal models of brain ischemia. However,
      the mechanisms underlying this effect remain unclear. The aim of the current
      study was to investigate whether post-weaning EE would be effective in preventing
      functional deficits and brain damage by affecting markers of synaptic plasticity
      in a neonatal rat model of hypoxia-ischemia (HI). We also examined the
      possibility that granulocyte-colony stimulating factor (G-CSF), a growth factor
      with known neuroprotective effects in a variety of experimental brain injury
      models, combined with EE stimulation could enhance the potential beneficial
      effect of EE. Seven-day-old Wistar rats of either sex were subjected to permanent
      ligation of the left common carotid artery followed by 60min of hypoxia (8% O2)
      and immediately after weaning (postnatal day 21) were housed in enriched
      conditions for 4weeks. A group of enriched-housed rats had been treated with G
      CSF immediately after HI for 5 consecutive days (50MUg/kg/day). Behavioral
      examination took place approximately at three months of age and included
      assessments of learning and memory (Morris water maze) as well as motor
      coordination (Rota-Rod). Infarct size and hippocampal area were estimated
      following behavioral assessment. Synaptic plasticity was evaluated based on BDNF
      and synaptophysin expression in the dorsal hippocampus. EE resulted in recovery
      of post-HI motor deficits and partial improvement of memory impairments which was
      not accompanied by reduced brain damage. Increased synaptophysin expression was
      observed in the contralateral to carotid ligation hemisphere. Hypoxia-ischemia
      alone or followed by enriched conditions did not affect BDNF expression which was
      increased only in enriched-housed normal rats. The combined therapy of G-CSF and
      EE further enhanced cognitive function compared to EE provided as monotherapy and
      prevented HI-induced brain damage by altering synaptic plasticity as reflected by
      increased synaptophysin expression. The above findings demonstrate that
      combination of neuroprotective treatments may result in increased protection and
      it might be a more effective strategy for the treatment of neonatal hypoxic
      ischemic brain injury.

PMID- 28495307
TI  - Event-related potentials during encoding: Comparing unitization to relational
      processing.
AB  - Context details are typically encoded into episodic memory via arbitrary
      associations to the relevant item, known as relational binding. Subsequent
      retrieval of those context details is primarily supported by recollection.
      Research suggests that context retrieval can rely on familiarity if the context
      details are "unitized" and thereby encoded as features of the item itself in a
      single new representation. With most investigations into unitization focusing on
      the contributions of familiarity and recollection during retrieval, little is
      known about unitization during encoding. In an effort to begin understanding
      unitization as an encoding process, we used event-related potentials to monitor
      brain activity while participants were instructed to encode words with color
      information using relational association or unitization. Results showed that
      unitization-based encoding elicited significantly more negative potentials in the
      left parietal region than relational encoding during presentation of the second
      segment of strategically-specific sentences. This difference continued through
      presentation of the third sentence segment, becoming less lateralized, and ended
      before the final two segments were presented. During the mental imagery period,
      unitization-based encoding elicited significantly more positive potentials than
      relational encoding in the first 200ms centrally and from 400 through 1000ms in
      left fronto-temporal and parieto-occipital regions. Our findings indicate that
      unitization and relational processing diverged at approximately the time that the
      context item was presented in the relational condition. During mental imagery,
      unitization diverged from relational processing immediately, suggesting that
      unitization affected the nature of the item representation, and possibly the
      brain regions involved, during memory encoding.

PMID- 28495308
TI  - Pharmaceutical prospects of naturally occurring quinazolinone and its
      derivatives.
AB  - Quinazolinones belong to a family of heterocyclic nitrogen compounds that have
      attracted increasing interest because of their broad spectrum of biological
      functions. This review describes three types of natural quinazolinones and their
      synthesized derivatives and summarizes their various pharmacological activities,
      including antifungal, anti-tumor, anti-malaria, anticonvulsant, anti-microbial,
      anti-inflammatory and antihyperlipidemic activities. In addition, structure
      activity relationships of quinazolinone derivatives are also reviewed.

PMID- 28495309
TI  - Group II introns in wheat mitochondria have degenerate structural features and
      varied splicing pathways.
AB  - Mitochondrial introns in flowering plant genes are virtually all classified as
      members of the group II ribozyme family although certain structural features have
      degenerated to varying degrees over evolutionary time. We are interested in the
      impact that unconventional intron architecture might have on splicing
      biochemistry in vivo and we have focused in particular on intronic domains V and
      VI, which for self-splicing introns provide a key component of the catalytic core
      and the bulged branchpoint adenosine, respectively. Notably, the two
      transesterification steps in classical group II splicing are the same as for
      nuclear spliceosomal introns and release the intron as a lariat. Using RT-PCR and
      circularized RT-PCR, we had previously demonstrated that several wheat
      mitochondrial introns which lack a branchpoint adenosine have atypical splicing
      pathways, and we have now extended this analysis to the full set of wheat
      introns, namely six trans-splicing and sixteen cis-splicing ones. A number of
      introns are excised using non-lariat pathways and interestingly, we find that
      several introns which do have a conventional domain VI also use pathways that
      appear to exploit other internal or external nucleophiles, with the lariat form
      being relatively minor. Somewhat surprisingly, several introns with weakly
      structured domain V/VI helices still exhibit classical lariat splicing,
      suggesting that accessory factors aid in restoring a splicing-competent
      conformation. Our observations illustrate that the loss of conventional group II
      features during evolution is correlated with altered splicing biochemistry in an
      intron-distinctive manner.

PMID- 28495310
TI  - Resveratrol inhibits urban particulate matter-induced COX-2/PGE2 release in human
      fibroblast-like synoviocytes via the inhibition of activation of NADPH
      oxidase/ROS/NF-kappaB.
AB  - Human fibroblast-like synoviocytes (FLSs) play a role in joint synovial
      inflammation in rheumatoid arthritis (RA). Some evidence indicates that
      particulate matter (PM) in air pollution could contribute to the progression of
      RA. However, more research is needed to clarify this relationship. Up-regulation
      of cyclooxygenase (COX)-2 and its metabolite prostaglandin E2 (PGE2) are
      implicated in various inflammatory diseases. Resveratrol, a polyphenol found
      mainly in grapes and red wine, has antioxidant and anti-inflammatory activities.
      In the present study, we demonstrated that resveratrol reduced PM-induced COX
      2/PGE2 expression in human FLSs, and attenuated PM-enhanced NADPH oxidase
      activity and ROS generation. In addition, PM induced Akt, ERK1/2, or p38 MAPK
      activation, which was inhibited by resveratrol. Finally, we demonstrated that PM
      enhanced NF-kappaB p65 phosphorylation and the NF-kappaB promoter activity, which
      were reduced by pretreatment with a ROS inhibitor or resveratrol. Thus, we
      concluded that resveratrol functions as a suppressor of PM-induced inflammatory
      signaling pathways by inhibiting COX-2/PGE2 expression.

PMID- 28495312
TI  - Considerations of critical quality attributes in the analytical comparability
      assessment of biosimilar products.
AB  - Based on experience in clinical trial approvals and marketing authorizations for
      biosimilar products in Korea, we suggest principles for the analytical
      comparability assessment of biosimilar products with respect to regulatory
      considerations. The composition and manufacturing processes of biosimilar
      products can differ from those of the reference product depending on the
      information available for the reference product and the time of product
      development; however, the analytical characteristics of biosimilar products
      should be highly similar to those of the reference product. Although
      manufacturing an identical product in terms of the quality profile is nearly
      impossible due to the high molecular weight and complex structure of biological
      products, the developer of the biosimilar product should attempt to establish a
      quality level as similar to that of the reference product as possible. When
      comparing the similarity of quality attributes, the criticality of the quality
      attributes and the characteristics of orthogonal quality attributes need to be
      considered carefully. Based on the results from the analytical comparability
      assessment, the comparability results of non-clinical and clinical studies should
      be evaluated before claiming biosimilarity to the reference product. In this
      review, we focus on quality attribute evaluation based on our regulatory
      experience.

PMID- 28495311
TI  - An Update on Memory Reconsolidation Updating.
AB  - The reactivation of a stored memory in the brain can make the memory transiently
      labile. During the time it takes for the memory to restabilize (reconsolidate)
      the memory can either be reduced by an amnesic agent or enhanced by memory
      enhancers. The change in memory expression is related to changes in the brain
      correlates of long-term memory. Many have suggested that such retrieval-induced
      plasticity is ideally placed to enable memories to be updated with new
      information. This hypothesis has been tested experimentally, with a translational
      perspective, by attempts to update maladaptive memories to reduce their
      problematic impact. We review here progress on reconsolidation updating studies,
      highlighting their translational exploitation and addressing recent challenges to
      the reconsolidation field.

PMID- 28495313
TI  - Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced
      seizures of male rats through hippocampal histamine increase.
AB  - OBJECTIVES: Seizures are epileptic manifestations that are intrinsically
      modulated through different neurotransmitters and receptor systems. Although
      glutamate increases excitation and hence seizures, it activates other systems
      which could potentially terminate seizures. Histamine originates from neurons of
      the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but
      the effect of local PH glutamate on hippocampal histamine content is unknown.
      Therefore, in this study, the effect of PH glutamate and the involvement of
      hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was
      studied. MATERIALS AND METHODS: OX2R antagonist (TCS OX2 29, 40nmol/1MUl, intra
      PH), AMPA/Kainate receptor antagonist (CNQX, 3mM, intra-PH) and glutamate (1mM)
      were injected bilaterally into PH using stereotaxic surgery. The intravenous PTZ
      infusion model was used to generate behavioral convulsions and the amount of
      hippocampal histamine content was then measured using a biochemical method.
      RESULTS: Administration of glutamate into PH decreased both seizure stage and the
      duration of tonic-clonic convulsion (TCC) with increasing TCC latency and
      hippocampal histamine content. Blocking OX2Rs alone or coinhibition of OX2Rs and
      AMPA/kainate receptors reversed these effects by increasing both seizure stage
      and TCC duration, and by decreasing both latency and consequent histamine
      content. CONCLUSIONS: Our findings suggest that glutamate administration into PH
      may control seizures (stages and duration) through increasing the hippocampal
      histamine content.

PMID- 28495314
TI  - A novel approach for construction of an inactivated typhoid vaccine candidate
      that effectively augments both humoral and cellular immune responses.
AB  - Salmonella enterica serovar Typhi ghost was constructed as a vaccine candidate
      against typhoid fever. An asd+ plasmid pJHL187 harboring a ghost cassette
      comprised of PhiX 174 E lysis gene stringently controlled under the convergent
      promotor components and was transformed into the asd gene-deleted mutant S. Typhi
      Ty21a strain (STG). Twenty female BALB/c mice randomly assigned into two groups
      were subcutaneously vaccinated at 5weeks of age to assess immunogenic
      characteristics of the constructed STG. The level of serum IgG in the immunized
      mice was significantly increased during the observational period (P<0.001) as the
      mice showed the significant elevation of secretory IgA at week 6 compared to
      those in the non-immunized mice (P<0.05). The CD3+CD4+ T cell subpopulation in
      the primed splenocytes showed approximately twofold increase in the immunized
      group. Further, the gene expression of various immunomodulatory cytokines
      associated with Th-1, Th-2 and Th-17 immunity was observed in in vitro
      restimulated splenocytes isolated from the immunized mice. Serum Bactericidal
      activity of antibodies produced in the rabbits immunized with STG was proved by
      the elimination of almost all of wild-type S. Typhi in the presence of exogenous
      complement over an hour at week 6 after the first immunization. The immuno
      stimulatory traits of STG demonstrated that the construct effectively enhanced
      the immunological responses, providing a potential of STG as the vaccine
      candidate against typhoid fever.

PMID- 28495315
TI  - Accelerated mass production of influenza virus seed stocks in HEK-293 suspension
      cell cultures by reverse genetics.
AB  - Despite major advances in developing capacities and alternative technologies to
      egg-based production of influenza vaccines, responsiveness to an influenza
      pandemic threat is limited by the time it takes to generate a Candidate Vaccine
      Virus (CVV) as reported by the 2015 WHO Informal Consultation report titled
      "Influenza Vaccine Response during the Start of a Pandemic". In previous work, we
      have shown that HEK-293 cell culture in suspension and serum free medium is an
      efficient production platform for cell culture manufacturing of influenza
      candidate vaccines. This report, took advantage of, recombinant DNA technology
      using Reverse Genetics of influenza strains, and advances in the large-scale
      transfection of suspension cultured HEK-293 cells. We demonstrate the efficient
      generation of H1N1 with the PR8 backbone reassortant under controlled bioreactor
      conditions in two sequential steps (transfection/rescue and
      infection/production). This approach could deliver a CVV for influenza vaccine
      manufacturing within two-weeks, starting from HA and NA pandemic sequences.
      Furthermore, the scalability of the transfection technology combined with the HEK
      293 platform has been extensively demonstrated at >100L scale for several
      biologics, including recombinant viruses. Thus, this innovative approach is
      better suited to rationally engineer and mass produce influenza CVV within
      significantly shorter timelines to enable an effective global response in
      pandemic situations.

PMID- 28495316
TI  - Effect of infectious bursal disease (IBD) vaccine on Salmonella Enteritidis
      infected chickens.
AB  - BACKGROUND: Chickens infected with both infectious bursal disease virus (IBDV)
      and Salmonella had higher mortality. In this work, we investigated the effect of
      IBDV vaccine (modified live-virus bursal disease vaccine, Nobilis strain 228E(r))
      on experimentally infected chickens with Salmonella Enteritidis (SE). METHODS:
      Four experimental groups were included in this study, negative control group,
      228E(r)group, 228E(r)+SE infected group, and SE infected group. Chickens were
      ocularly administrated 228E(r) at 12days of age and orally infected with S.
      Enteritidis at 13days of age. Sera, intestinal fluid, blood, cloacal swabs and
      tissue samples were collected at 1, 2 and 3weeks post vaccination (PV). RESULTS:
      The recorded mortalities were higher in the 228E(r)+SE infected group, compared
      to the SE infected group. The anti-S. Enteritidis serum antibody titer and the
      intestinal mucosal IgA level were higher in the SE infected group at 2 and 3weeks
      PV, compared to 228E(r)+SE infected group. S. Enteritidis fecal shedding and
      organ colonization were significantly higher in the 228E(r)+SE infected group
      than the SE infected group at 2 and 3weeks PV. The 228E(r)+SE group had
      significantly lower bursa to body weight ratios at 2 and 3weeks PV, as well as
      had higher bursal lesion scores than the SE infected group. IBDV vaccine
      depressed the specific-SE systemic and mucosal antibody responses, but did not
      affect the specific-SE cellular immune responses. CONCLUSION: Chickens
      administrated IBDV vaccine, followed by S. Enteritidis infection, could cause a
      significant effect on the bursa of Fabricius, resulting in failure of systemic
      and mucosal antibody responses to the S. Enteritidis and reduce the elimination
      and the clearance of S. Enteritidis.

PMID- 28495318
TI  - The reno-cardiovascular connection in the patient with Diabetes mellitus: What's
      new?

PMID- 28495317
TI  - Cross-sectional study involving healthcare professionals in a Vaccinia virus
      endemic area.
AB  - Orthopoxviruses (OPV) are emerging viruses with great importance in human and
      veterinary medicine, such as Vaccinia virus (VACV), which causes outbreaks of
      bovine vaccinia (BV) in South America. The clinical aspects of BV are similar to
      other vesicular infections, complicating the clinical diagnosis. This cross
      sectional study evaluated the knowledge of Healthcare Professionals about BV and
      revealed their unpreparedness about BV in a VACV hyper-endemic area in Brazil,
      highlighting the public health issues associated with VACV infections. This study
      presents an opportunity to discuss the importance of vaccination for healthcare
      professionals who work in areas of VACV circulation and brings an educational
      measure on VACV infections for health professionals around the world.

PMID- 28495319
TI  - Clinical characteristics and mortality in patients treated in a Multidisciplinary
      Diabetic Foot Unit.
AB  - BACKGROUND AND OBJECTIVE: This study reviews the clinical characteristics of
      patients with diabetic foot ulcer treated in a Multidisciplinary Diabetic Foot
      Unit (MDFU) and analyzes the mortality and factors associated with its survival.
      MATERIAL AND METHODS: Data from all patients who attended the MDFU for the first
      time for a diabetic foot ulcer during the 2008-2014 period were analized. The
      patients were followed until their death or until June 30, 2016, for up to 8
      years. RESULTS: A total of 345 patients were included, with a median age (P25
      P75) of 71 (61.5-80) years, and 321 (93%) had type 2 diabetes. They were
      characterized as patients with inadequate glycemic control, 48% had HbA1c >= 8%
      and high prevalence of chronic complications: 60.2% retinopathy, 43.8%
      nephropathy and 47.2% ischemic heart disease and/or cerebrovascular disease. A
      total of 126 (36.5%) patients died and 69 (54.8%) were due to cardiovascular
      disease. Survival measured by Kaplan-Meier declined over time to 69, 60 and 45%
      at 3, 5 and 7 years respectively. Cox's multivariate regression analysis showed
      the following variables associated with mortality, HR (95% CI): age 1.08 (1.05
      1.11); previous amputation 2.24 (1.34-3.73); active smoking 2.10 (1.12-3.97);
      cerebrovascular disease 1.75 (1.05-2.92); renal dysfunction 1.65 (1.04-2.61) and
      ischemic heart disease 1.60 (1.01-2.51). CONCLUSIONS: Patients with diabetic foot
      ulcer are characterized by high morbidity and mortality, with cardiovascular
      disease being the most frequent cause of death. It is necessary to pay more
      attention to this risk group, tailoring objectives and treatments to their
      situation and life expectancy.

PMID- 28495320
TI  - Comparison of 2 intravenous insulin protocols: Glycemia variability in critically
      ill patients.
AB  - OBJECTIVE: Glycemic variability is an independent predictor of mortality in
      critically ill patients. The objective of this study was to compare two
      intravenous insulin protocols in critically ill patients regarding the glycemic
      variability. MATERIAL AND METHODS: This was a retrospective observational study
      performed by reviewing clinical records of patients from a Critical Care Unit for
      4 consecutive months. First, a simpler Scale-Based Intravenous Insulin Protocol
      (SBIIP) was reviewed and later it was compared for the same months of the
      following year with a Sliding Scale-Based Intravenous Insulin Protocol (SSBIIP).
      All adult patients admitted to the unit during the referred months were included.
      Patients in whom the protocol was not adequately followed were excluded. A total
      of 557 patients were reviewed, of whom they had needed intravenous insulin 73 in
      the first group and 52 in the second group. Four and two patients were excluded
      in each group respectively. RESULTS: Glycemic variability for both day 1 (DS1)
      and total stay (DST) was lower in SSBIIP patients compared to SBIIP patients: SD1
      34.88 vs 18.16 and SDT 36.45 vs 23.65 (P<.001). CONCLUSION: A glycemic management
      protocol in critically ill patients based on sliding scales decreases glycemic
      variability.

PMID- 28495321
TI  - Increased salivary oxidative stress parameters in patients with type 2 diabetes:
      Relation with periodontal disease.
AB  - OBJECTIVE: The aim of this study was to determine whether there are differences
      in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2)
      and healthy non-diabetic patients, and whether this oxidative stress is
      associated with the presence of periodontal disease in diabetic patients.
      MATERIAL AND METHODS: This observational study included 70 patients divided into
      three groups according to metabolic control levels: 19 non-diabetic patients
      (control group); 24 patients with good metabolic control (HbA1c<7%), and 27
      patients DM2 with poor metabolic control (HbA1c>7%). The following oxidative
      stress parameters were measured in all subjects: glutathione peroxidase (GPx),
      glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione
      (GSSG). Periodontal health was determined by means of the community periodontal
      index (CPI) recommended by the WHO. RESULTS: The diabetic group with good
      metabolic control showed a significant increase in GPx and GRd activity in
      comparison with the control group (P<.001). The activity of the enzymes measured
      was significantly less in patients with poor metabolic control in comparison with
      the control group and well-controlled diabetic groups (P<.001). Both diabetic
      groups showed higher GSSG/GSH quotients and CPI in comparison with the control
      group, and both parameters were significantly higher in diabetic patients with
      poor metabolic control in comparison with well-controlled diabetic patients.
      CONCLUSIONS: Poor metabolic control in DM2 patients is associated with higher
      levels of salivary oxidative stress and worse periodontal health.

PMID- 28495322
TI  - Prevalence and control of type 2 diabetes mellitus among primary care physicians
      in Spain. PRISMA Study.
AB  - OBJECTIVE: To describe the prevalence of known and ignored type 2 diabetes
      mellitus (T2DM) among primary care physicians (PCP), as well as the treatment
      used and the degree of metabolic control reached. MATERIAL AND METHODS:
      Descriptive cross-sectional study on national level. The participants were
      randomly selected PCPs, members of the redGDPS Foundation. A total of 495 PCP
      were enrolled. Capillary HbA1c measurement was done with a A1CNow+(r) device and
      a diabetes-related survey specifically designed for the study was administered to
      the participants. RESULTS: The total prevalence of T2DM was 11.1% (95% CI 8.33
      13.9) (known disease 8,1% and ignored disease 3.0%). The prevalence of
      prediabetes was 16.2% (95% CI 13.0-19.4). A total of 62.5% of PCPs with known
      T2DM reached HbA1c<7% and 15% had HbA1c>8.5%. Control of blood pressure
      (BP<140/90mmHg) was reached in 87.5% and control of LDL cholesterol<130mg/dl with
      no history of cardiovascular disease was reached in 88.6% of cases of known T2DM.
      In the PCPs with a history of macrovascular disease, good control of LDL was
      reached in 42.9% of the cases. A total of 12.5% were active smokers. A total of
      71.4% of PCPs with known T2DM self-treated their own disease, usually with 2 or
      more drugs (51.4%). The most commonly used drug was metformin (74.3%) followed by
      iDPP4 (48.6%). CONCLUSIONS: PCPs with T2DM have better metabolic control than the
      general population. It is necessary to study whether PCPs with T2DM may have
      greater adherence to treatment and do they achieve a better metabolic control.

PMID- 28495323
TI  - Criteria for frusemide reduction or withdrawal.

PMID- 28495324
TI  - Biology of the somatotroph axis (after the pituitary).
AB  - Normal growth requires that pituitary-secreted growth hormone (GH) bind to its
      specific receptor and activate a complex signaling cascade, leaving to production
      of insulin-like growth factor-I (IGF-I), which, in turn, activates its own
      receptor (IGF1R). The GH receptor (GHR) is preformed as a dimer and is
      transported in a nonligand bound state to the cell surface. Binding of GH to the
      GHR dimer, results in a conformational change of the dimer, activation of the
      intracellular Janus Kinase 2 (JAK2) and phosphorylation of signal transducer and
      activator of transcription (STAT) 5B. Phosphorylated STAT5B dimers are then
      translocated to the nucleus, where they transcriptionally activate multiple
      genes, including those for IGF-I, IGF binding protein-3 and the acid-labile
      subunit (ALS).

PMID- 28495325
TI  - Endocrine perturbations in POEMS syndrome: Misunderstood features of a rare
      paraneoplastic syndrome.

PMID- 28495326
TI  - Bone dysplasia.
AB  - Bone dysplasia is a large group that encompasses 436 rare diseases. Many of them
      are characterized by short stature or decreased growth velocity during puberty.
      The diagnosis of short stature due to skeletal dysplasia relies on (i) physical
      features such as disproportionate trunk/limbs, short limbs or extremities and/or
      stocky build, (ii) radiographic features to analyze mineralization, maturation
      and bone morphology, and (iii) whenever possible, the genetic characterization.
      Bone dysplasia mostly affect many organs, and therefore require multidisciplinary
      follow-up and care. The role of the pediatric endocrinologist is to assess the
      growth potential of these patients in coordination with the other caregivers,
      offer the best management of the growth to limit the psychosocial consequences of
      the extreme short stature and bone deformities.

PMID- 28495327
TI  - Vocal Change Patterns During a Teaching Day: Inter- and Intra-subject
      Variability.
AB  - OBJECTIVES: To describe the mean voice changes of 22 female teachers during a
      typical workday, examine the inter- and intra-subject variability, and establish
      a typology of different voice patterns during the workday. METHODS: For each
      participant, fundamental frequency (F0), harmonics-to-noise ratio (HNR), jitter,
      and shimmer were measured on sustained vowels at the beginning and at the end of
      the workday, at three different times during the school year. RESULTS: The group
      mean pattern showed significant increases in F0 and HNR during the workday and
      significant decreases in jitter and shimmer. However, considerable inter- and
      intra-subject variability was observed. Based on the variation in the acoustic
      parameters during the workday, three different voice patterns were identified.
      The first is characterized by a greater F0 increase during the day, interpreted
      as a common, appropriate adaptation to vocal load. The second is characterized by
      a greater increase in HNR during the day and greater decreases in jitter and
      shimmer, interpreted as hyperfunctional voice production. The third is
      characterized by greater decreases in F0 and HNR and greater increases in jitter
      and shimmer, suggesting acute inflammation or muscle fatigue following the
      workday. CONCLUSIONS: The observed variety of vocal patterns during the workday
      emphasizes the need to study this phenomenon individually and target different
      types of behaviors to develop tailored prevention and treatment methods.

PMID- 28495328
TI  - Flow Glottogram and Subglottal Pressure Relationship in Singers and Untrained
      Voices.
AB  - This article combines results from three earlier investigations of the glottal
      voice source during phonation at varying degrees of vocal loudness (1) in five
      classically trained baritone singers (Sundberg et al., 1999), (2) in 15 female
      and 14 male untrained voices (Sundberg et al., 2005), and (3) in voices rated as
      hyperfunctional by an expert panel (Millgard et al., 2015). Voice source data
      were obtained by inverse filtering. Associated subglottal pressures were
      estimated from oral pressure during the occlusion for the consonant /p/. Five
      flow glottogram parameters, (1) maximum flow declination rate (MFDR), (2) peak-to
      peak pulse amplitude, (3) level difference between the first and the second
      harmonics of the voice source, (4) closed quotient, and (5) normalized amplitude
      quotient, were averaged across the singer subjects and related to associated MFDR
      values. Strong, quantitative relations, expressed as equations, are found between
      subglottal pressure and MFDR and between MFDR and each of the other flow
      glottogram parameters. The values for the untrained voices, as well as those for
      the voices rated as hyperfunctional, deviate systematically from the values
      derived from the equations.

PMID- 28495329
TI  - Dynamics of the Driving Force During the Normal Vocal Fold Vibration Cycle.
AB  - Intraglottal pressure is the driving force of vocal fold vibration.
      Theoretically, simultaneous quantification of glottal area and transglottal
      airflow allows the calculation of the intraglottal pressure waveform during a
      single vibration cycle. In this study, we show that, by combining
      photoglottography (transglottal light transmission) and airflow (Rothenberg mask)
      measurements during sustained vocal emissions in vivo, the intraglottal pressure
      wave can be approximated in a way similar to what has been done in models. The
      results confirm in vivo that the intraglottal pressure is systematically larger
      during the opening phase than during the closing phase, so that over one whole
      cycle, the driving force performs net positive work, accounting for sustained
      vocal fold motion. A component of this driving force asymmetry is related to
      vocal tract inertance, which also accounts for the skewing of the airflow
      waveform compared with the area waveform. Furthermore, the intraglottal pressure
      ratio (opening:closing) increases with voicing intensity, reaches a maximum
      around 76 dB, and significantly decreases at higher intensities. This rise and
      fall suggests that there is a range of intensity values in which, mechanically, a
      maximum of the driving force is imparted to the vocal fold mass. This finding
      could have implications for voice economy in professional speakers.

PMID- 28495330
TI  - Relationships between age and microarchitectural descriptors of iliac trabecular
      bone determined by microCT.
AB  - AIM: Estimation of age at death is a major issue in anthropology. The main
      anthropological histological methods propose studying the architecture of
      cortical bone. In bone histomorphometry, researches on metabolic bone diseases
      have provided normative tables for trabecular bone volume (BV/TV) according to
      age and gender of individuals on trans-iliac bone biopsies. We have used microCT,
      a non-destructive tool for measuring bone volume and trabecular descriptors to
      compare the French tables to a series of forensic anthropological population and
      if the two iliac bones could be used interchangeably. METHODOLOGY: Coxal bone of
      a personal forensic collection whose age and gender were known (DNA
      identification) were used. Bone samples, centered on the same area than bone
      biopsy. MicroCT (pixel size: 36MUm) was used to measure BV/TV and morphometric
      trabecular parameters of microarchitecture. An adjusted Z-score was calculated
      for BV/TV to compare with normative tables and a right/left comparison of
      trabecular parameters was provided. RESULTS: Twenty-seven iliac bones, which 20
      forming 10 complete pelvises, aged between 24 and 73y.o. (average of 47.7 y.o.)
      were used. All adjusted Z-score were within normal values. There was a strong
      positive correlation between right and left sides for Tb.Th, Tb.N and Tb.Sp, but
      an insignificant correlation was obtained for BV/TV. CONCLUSION: Normative tables
      between age and BV/TV are valid and therefore usable in anthropology. They may
      represent an alternative to determine the age at death. Nevertheless, it requires
      a precise technique that could be a drawback in current practice.

PMID- 28495331
TI  - Corrigendum to "Land use regression modelling of air pollution in high density
      high rise cities: A case study in Hong Kong" [Sci. Total Environ. 592 (2017) 306
      315].

PMID- 28495332
TI  - The neural correlates of theory of mind and their role during empathy and the
      game of chess: A functional magnetic resonance imaging study.
AB  - Chess involves the capacity to reason iteratively about potential intentional
      choices of an opponent and therefore involves high levels of explicit theory of
      mind [ToM] (i.e. ability to infer mental states of others) alongside clear,
      strategic rule-based decision-making. Functional magnetic resonance imaging was
      used on 12 healthy male novice chess players to identify cortical regions
      associated with chess, ToM and empathizing. The blood-oxygenation-level-dependent
      (BOLD) response for chess and empathizing tasks was extracted from each ToM
      region. Results showed neural overlap between ToM, chess and empathizing tasks in
      right-hemisphere temporo-parietal junction (TPJ) [BA40], left-hemisphere superior
      temporal gyrus [BA22] and posterior cingulate gyrus [BA23/31]. TPJ is suggested
      to underlie the capacity to reason iteratively about another's internal state in
      a range of tasks. Areas activated by ToM and empathy included right-hemisphere
      orbitofrontal cortex and bilateral middle temporal gyrus: areas that become
      active when there is need to inhibit one's own experience when considering the
      internal state of another and for visual evaluation of action rationality.
      Results support previous findings, that ToM recruits a neural network with each
      region sub-serving a supporting role depending on the nature of the task itself.
      In contrast, a network of cortical regions primarily located within right- and
      left-hemisphere medial-frontal and parietal cortex, outside the internal
      representational network, was selectively recruited during the chess task. We
      hypothesize that in our cohort of novice chess players the strategy was to employ
      an iterative thinking pattern which in part involved mentalizing processes and
      recruited core ToM-related regions.

PMID- 28495333
TI  - Sensory experience-dependent formation of perineuronal nets and expression of Cat
      315 immunoreactive components in the mouse somatosensory cortex.
AB  - Perineuronal nets (PNNs) are structures of extracellular matrix molecules
      surrounding the cell bodies and proximal dendrites of certain neurons. While PNNs
      are present throughout the mouse cerebral cortex, recent studies have shown that
      the components differ among cortical sub-regions and layers, suggesting region
      specific functions. Parvalbumin-expressing interneurons (PV neurons) may be
      important regulators of cortical plasticity during the early "critical period"
      that is sensitive to sensory input. Here we examined the distribution and
      developmental functions of PNN components associated with PV neurons in the
      somatosensory cortex during the critical period. Aggrecan, brevican, neurocan,
      phosphacan, and tenascin-R were identified as PNN components in the mouse
      somatosensory cortex. High-magnification analysis revealed that some lectin
      Wisteria floribunda agglutinin (WFA)-reactive molecules did not co-localize with
      monoclonal antibody Cat-315 recognition molecules around the cell body. During
      postnatal development, Cat-315-positive (Cat-315+) PNNs appeared later than PNNs
      binding to the lectin WFA (WFA+ PNNs). These WFA+ PNNs changed from granular-like
      to reticular-like structures during normal cortical development, while this
      transition was delayed by sensory deprivation. This study indicates that the
      formation of reticular-like WFA+ PNNs is dependent on sensory experience in the
      mouse somatosensory cortex. We suggest that Cat-315+ molecules and WFA expression
      in PNNs are involved in the early critical period of input-dependent cortical
      plasticity.

PMID- 28495334
TI  - Found in Translation: Applying Lessons from Model Systems to Strigolactone
      Signaling in Parasitic Plants.
AB  - Strigolactones (SLs) are small molecules that act as endogenous hormones to
      regulate plant development as well as exogenous cues that help parasitic plants
      to infect their hosts. Given that parasitic plants are experimentally challenging
      systems, researchers are using two approaches to understand how they respond to
      host-derived SLs. The first involves extrapolating information on SLs from model
      genetic systems to dissect their roles in parasitic plants. The second uses
      chemicals to probe SL signaling directly in the parasite Striga hermonthica.
      These approaches indicate that parasitic plants have co-opted a family of
      alpha/beta hydrolases to perceive SLs. The importance of this genetic and
      chemical information cannot be overstated since parasitic plant infestations are
      major obstacles to food security in the developing world.

PMID- 28495335
TI  - 50 years of prehospital resuscitation: Reflection and celebration.

PMID- 28495336
TI  - The ability of older adults to use customized online medical databases to improve
      their health-related knowledge.
AB  - INTRODUCTION: Patient compliance with medical advice and recommended treatment
      depends on perception of health condition, medical knowledge, attitude, and self
      efficacy. This study investigated how use of customized online medical databases,
      intended to improve knowledge in a variety of relevant medical topics, influenced
      senior adults' perceptions. METHOD: Seventy-nine older adults in residence homes
      completed a computerized, tablet-based questionnaire, with medical scenarios and
      related questions. Following an intervention, control group participants answered
      questions without online help while an experimental group received internet links
      that directed them to customized, online medical databases. RESULTS: Medical
      knowledge and test scores among the experimental group significantly improved
      from pre- to post-intervention (p<0.0001) and was higher in comparison with the
      control group (p<0.0001). No significant change occurred in the control group.
      CONCLUSION: Older adults improved their knowledge in desired medical topic areas
      using customized online medical databases. The study demonstrated how such
      databases help solve health-related questions among older adult population
      members, and that older patients appear willing to consider technology usage in
      information acquisition.

PMID- 28495337
TI  - Development and validation of detailed clinical models for nursing actions in
      perinatal care.
AB  - OBJECTIVES: The aim of this study was to develop and evaluate detailed clinical
      models (DCMs) for nursing actions in perinatal care. We propose the use of action
      target dyads as entities in DCMs for nursing actions. METHODS: We identified
      action and target concepts, attributes, and value sets by analyzing nursing
      documentation and reviewing the wider literature, in addition to published
      standards and models. We developed the DCMs by linking entities, attributes, and
      value sets. DCMs were classified by action type based on the Clinical Care
      Classification, and by target type based on the axes of the International
      Classification for Nursing Practice (ICNP). Attributes in the DCMs were also
      classified by ICNP axes. The quality of the DCMs was evaluated by domain experts,
      and their coverage was evaluated by mapping narrative nursing statements.
      RESULTS: Nursing DCMs consisting of 233 entities (dyads comprising 34 action and
      212 target concepts), 214 attributes and 541 values were developed. The most
      frequent action type was hands-on care (43.3%). The focus axis was used most
      frequently for the targets (51.9%) and attributes (38.8%). The quality scores of
      the DCMs ranged from 0.80 to 0.96. Most (174/192; 90.6%) of the statements were
      fully mapped, while 7 (3.7%) were partially mapped and 11 (5.7%) were not mapped.
      We modified the DCMs in accordance with these results. CONCLUSIONS: In total, 240
      DCMs were developed with action-target dyads as entities. The DCMs developed in
      this study could be implemented in an electronic nursing record system to enhance
      nursing practices and ensure semantic interoperability of nursing data.

PMID- 28495338
TI  - Adoption of medication alert systems in hospital outpatient departments in
      Taiwan.
AB  - OBJECTIVE: The adoption of medication alert systems in the health care sector
      varies among regions. In Taiwan, the health authority introduced policies in 2005
      to encourage the adoption of medication alert systems in hospitals. This study
      aimed to understand the adoption of medication alert systems in the outpatient
      departments of hospitals in Taiwan using a nationwide survey. METHODS: A
      questionnaire was developed and mailed to 380 accredited general hospitals in
      Taiwan in 2013. The information collected from the questionnaire concerning the
      outpatient department included (1) the time of adoption of a medication alert
      system; (2) the operation of individual alert functions: availability,
      management, and stability; and (3) hospital characteristics: accreditation level,
      teaching status, ownership, and number of beds. RESULTS: A total of 216 hospitals
      completed and returned the questionnaire, corresponding to a response rate of
      56.8%. The adoption rate of medication alert systems in hospital outpatient
      departments increased from less than 10% in 1997-95.83% in 2012. Approximately
      two-thirds of the hospitals developed and maintained the alert systems
      independently or collaboratively with vendors. Teaching and large hospitals
      tended to develop more advanced alert functions such as drug-drug interaction
      functions. Improving the safety and quality of pharmaceutical services and
      meeting the policy requirements are reasons for hospitals to establish medication
      alert systems. CONCLUSION: The adoption rate of medication alert systems reached
      95% in accredited general hospitals in Taiwan. Government policy and available
      health information professionals and vendors may somewhat contribute to the high
      adoption rate.

PMID- 28495339
TI  - User experience analysis of an eHealth system for tuberculosis in resource
      constrained settings: A nine-country comparison.
AB  - BACKGROUND: e-TB Manager, a web-based eHealth system has been successfully
      institutionalized in 10 resource-constrained countries that account for one-third
      of the world's tuberculosis (TB) burden, but user experience has never been
      evaluated. METHODS: A cross-sectional, anonymous survey in eight unique languages
      based on the targeted countries. e-TB Manager users included nurses, doctors,
      pharmacists, statisticians/data officers, laboratory professionals/assistants,
      health workers, and administrators. RESULTS: With an 86.3% completion rate for
      all required questions, 1,511 completed responses were analyzed. Users had worked
      in TB programs for a median of five years and had used e-TB Manager for a median
      of two years. Overall, 60.2% of respondents were female, 65% were clustered in
      the age groups of 30-39 and 40-49 years old, and nearly half (49%) were using e
      TB Manager at the district and sub-district levels of a country's health system.
      Older respondents aged over 50, regardless of location and with at least 6 or
      more years of experience in public-sector TB programs, had higher mean
      satisfaction scores than did their younger counterparts. Overall, those who had
      used e-TB Manager for more than two years had significantly higher mean scores
      for the majority of the survey statements than did those who had used e-TB
      Manager for less than two years. Ukraine had significantly higher mean scores for
      finding patient information available in e-TB Manager and in its benefit in
      improving patient care compared to Brazil, Armenia, Nigeria, and Indonesia.
      Brazil and Ukraine differed significantly from five other countries in that they
      did not need additional training, thereby demonstrating their institutional
      capacity after more than five years of using e-TB Manager. CONCLUSION: Although
      users gave high ratings to e-TB Manager in terms of helping to improve patient
      care, found it to be reliable, and were generally satisfied, there is need for a
      combination of refresher training and e-learning methodologies to keep pace with
      programmatic changes.

PMID- 28495340
TI  - Investigating the determinants of Chinese adult children's intention to use
      online health information for their aged parents.
AB  - BACKGROUND: The increasing number of older people and the dissemination of health
      information via the Internet have emerged and both are challenging to Chinese
      society. Available online health information highlights the importance of
      decision making processes, specially in relation to the elderly who almost have
      no online presence and depend on their adult children's help. The researchers
      mostly focus on parents' health information search for their children, however,
      they overlook the adult children's intention to use online health information for
      their aged parents. OBJECTIVE: This study fills this gap by extending the Theory
      of Planned Behavior (TPB) to identify the determinants of adult children's
      intention to use online health information for their aged parents. METHOD:
      Relying on survey method, the data were collected from teachers and students at
      different participating Universities in Wuhan, China. The Partial Least Squares
      (PLS), a structural equation modeling technique, was employed to test the
      research model. RESULTS: This study found that attitude, subjective norm,
      perceived behavioral control and risk (p<0.05) were the predictors of intention
      to use online health information, whereas, trust (p>0.05) was not listed among
      the predictors. CONCLUSIONS: This study is a significant addition to the
      literature, in that it confirms the utility of the TPB with additional variables
      in predicting adults' children intention to use online health information for
      their aged parents.

PMID- 28495341
TI  - Estimation of the prevalence of adverse drug reactions from social media.
AB  - This work aims to estimate the degree of adverse drug reactions (ADR) for
      psychiatric medications from social media, including Twitter, Reddit, and
      LiveJournal. Advances in lightning-fast cluster computing was employed to process
      large scale data, consisting of 6.4 terabytes of data containing 3.8 billion
      records from all the media. Rates of ADR were quantified using the SIDER database
      of drugs and side-effects, and an estimated ADR rate was based on the prevalence
      of discussion in the social media corpora. Agreement between these measures for a
      sample of ten popular psychiatric drugs was evaluated using the Pearson
      correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel
      neural learning framework, was utilized to improve the coverage of variants of
      ADR terms in the unstructured text by identifying syntactically or semantically
      similar terms. Improved correlation coefficients, between 0.29 and 0.59,
      demonstrates the capability of advanced techniques in machine learning to aid in
      the discovery of meaningful patterns from medical data, and social media data, at
      scale.

PMID- 28495342
TI  - A method for cohort selection of cardiovascular disease records from an
      electronic health record system.
AB  - INTRODUCTION: An electronic healthcare record (EHR) system, when used by
      healthcare providers, improves the quality of care for patients and helps to
      lower costs. Information collected from manual or electronic health records can
      also be used for purposes not directly related to patient care delivery, in which
      case it is termed secondary use. EHR systems facilitate the collection of this
      secondary use data, which can be used for research purposes like observational
      studies, taking advantage of improvement in the structuring and retrieval of
      patient information. However, some of the following problems are common when
      conducting a research using this kind of data: (i) Over time, systems and data
      storage methods become obsolete; (ii) Data concerns arise since the data is being
      used in a context removed from its original intention; (iii) There are privacy
      concerns when sharing data about individual subjects; (iv) The partial
      availability of standard medical vocabularies and natural language processing
      tools for non-English language limits information extraction from structured and
      unstructured data in the EHR systems. A systematic approach is therefore needed
      to overcome these, where local data processing is performed prior to data
      sharing. METHOD: The proposed study describes a local processing method to
      extract cohorts of patients for observational studies in four steps: (1) data
      reorganization from an existing local logical schema into a common external
      schema over which information can be extracted; (2) cleaning of data, generation
      of the database profile and retrieval of indicators; (3) computation of derived
      variables from original variables; (4) application of study design parameters to
      transform longitudinal data into anonymized data sets ready for statistical
      analysis and sharing. Mapping from the local logical schema into a common
      external schema must be performed differently for each EHR and is not subject of
      this work, but step 2, 3 and 4 are common to all EHRs. The external schema
      accepts parameters that facilitate the extraction of different cohorts for
      different studies without having to change the extraction algorithms, and ensures
      that, given an immutable data set, can be done by the idempotent process.
      Statistical analysis is part of the process to generate the results necessary for
      inclusion in reports. The generation of indicators to describe the database
      allows description of its characteristics, highlighting study results. The set
      extraction/statistical processing is available in a version controlled repository
      and can be used at any time to reproduce results, allowing the verification of
      alterations and error corrections. This methodology promotes the development of
      reproducible studies and allows potential research problems to be tracked upon
      extraction algorithms and statistical methods RESULTS: This method was applied to
      an admissions database, SI3, from the InCor-HCFMUSP, a tertiary referral hospital
      for cardiovascular disease in the city of Sao Paulo, as a source of secondary
      data with 1116848 patients records from 1999 up to 2013. The cleaning process
      resulted in 313894 patients records and 27698 patients in the cohort selection,
      with the following criteria: study period: 2003-2013, gender: Male, Female,
      age:>=18years old, at least 2 outpatient encounters, diagnosis of cardiovascular
      disease (ICD-10 codes: I20-I25, I64-I70 and G45). An R script provided
      descriptive statistics of the extracted cohort. CONCLUSION: This method
      guarantees a reproducible cohort extraction for use of secondary data in
      observational studies with enough parameterization to support different study
      designs and can be used on diverse data sources. Moreover it allows observational
      electronic health record cohort research to be performed in a non-English
      language with limited international recognized medical vocabulary.

PMID- 28495343
TI  - Multimedia patient education to assist oral impression taking during dental
      treatment: A pilot study.
AB  - INTRODUCTION: Proper cooperation between patient and dentist is of great help to
      make a good oral impression. However, patients are frequently confused when
      information is given through traditional verbal description. The present study
      compared the effectiveness of the multimedia information delivery ways with the
      traditional verbal manner on patients' understanding level in oral impression
      taking. METHODS: The recruited 191 participating patients were randomly assigned
      to the control group (the verbal group) and two intervention groups (the video
      group and the picture group) according to the information delivery manner. After
      intervention, the patients' understanding degree was measured by questionnaire
      and performance evaluation of behavior feedback on the provided information
      quantitatively. Also, patients' self-assessment of satisfaction was interviewed
      by telephone. All data was analyzed by SPSS 14.0 software, and p<=0.05 was set as
      significant difference in advance. RESULTS: One-Way ANOVA and Chi-square showed
      there were no statistically significant differences in the mean age, gender
      composition, and educational level among the three groups (P>0.05). In both
      questionnaire assessment and performance evaluation, One-Way ANOVA followed by
      LSD indicate that the video group gained a higher score than the verbal group or
      the picture group (P<0.05). The questionnaire score in the picture group is
      significantly higher than in the control group (P<0.05), but no significant
      difference was shown between these two groups in patients' performance evaluation
      (P>0.05). Higher percentage of satisfaction was reported by patients in the two
      multimedia groups than that in the control group. DISCUSSION: Oral impression
      taking is a consecutive process that requires action cooperation between dentists
      and patients simultaneously. This particularity makes it more suitable for
      multimedia delivery. The delivery of tailored information using multimedia in
      this study was favored by most patients and could improve the degree of patient
      understanding of the oral impression taking procedures.

PMID- 28495344
TI  - Does adoption of electronic health records improve the quality of care management
      in France? Results from the French e-SI (PREPS-SIPS) study.
AB  - BACKGROUND: Electronic health records (EHR) are increasingly being adopted by
      healthcare systems worldwide. In France, the "Hopital numerique 2012-2017"
      program was implemented as part of a strategic plan to modernize health
      information technology (HIT), including the promotion of widespread EHR use. With
      significant upfront investment costs as well as ongoing operational expenses, it
      is important to assess this system in terms of its ability to result in
      improvements in hospital performances. OBJECTIVE: The aim of this study was to
      evaluate the impact of EHR use on the quality of care management in acute care
      hospitals throughout France. METHODS: This retrospective study was based on data
      derived from three national databases for the year 2011: IPAQSS (indicators of
      improvement in the quality and the management of healthcare, "IPAQSS"), Hospi
      Diag (French hospital performance indicators), and the national accreditation
      database. Several multivariate models were used to examine the association
      between the use of EHRs and specific EHR features with four quality indicators:
      the quality of patient record, the delay in sending information at hospital
      discharge, the pain status evaluation, and the nutritional status evaluation,
      while also adjusting for hospital characteristics. RESULTS: The models revealed a
      significant positive impact of EHR use on the four quality indicators.
      Additionally, they showed a differential impact according to the functionality of
      the element of the health record that was computerized. All four quality
      indicators were also impacted by the type of hospital, the geographical region,
      and the severity of the pathology. CONCLUSION: These results suggest that, to
      improve the quality of care management in hospitals, EHR adoption represents an
      important lever. They complete previous work dealing with EHR and the
      organizational performance of hospital surgical units.

PMID- 28495345
TI  - The Georges Pompidou University Hospital Clinical Data Warehouse: A 8-years
      follow-up experience.
AB  - BACKGROUND: When developed jointly with clinical information systems, clinical
      data warehouses (CDWs) facilitate the reuse of healthcare data and leverage
      clinical research. OBJECTIVE: To describe both data access and use for clinical
      research, epidemiology and health service research of the "Hopital Europeen
      Georges Pompidou" (HEGP) CDW. METHODS: The CDW has been developed since 2008
      using an i2b2 platform. It was made available to health professionals and
      researchers in October 2010. Procedures to access data have been implemented and
      different access levels have been distinguished according to the nature of
      queries. RESULTS: As of July 2016, the CDW contained the consolidated data of
      over 860,000 patients followed since the opening of the HEGP hospital in July
      2000. These data correspond to more than 122 million clinical item values, 124
      million biological item values, and 3.7 million free text reports. The ethics
      committee of the hospital evaluates all CDW projects that generate secondary data
      marts. Characteristics of the 74 research projects validated between January 2011
      and December 2015 are described. CONCLUSION: The use of HEGP CDWs is a key
      facilitator for clinical research studies. It required however important
      methodological and organizational support efforts from a biomedical informatics
      department.

PMID- 28495346
TI  - Changing the electronic request form proves to be an effective tool for
      optimizing laboratory test utilization in the emergency department.
AB  - OBJECTIVES: Appropriate laboratory utilization more often than not needs to be
      initiated by the laboratory. This study was performed to analyze the impact on
      test ordering patterns in the emergency department obtained by omitting certain
      tests from the electronic tick box request form. The tests could still be ordered
      by writing the full name of the test or by a phone call. METHODS: Erythrocyte
      sedimentation rate (ESR), fibrinogen, aspartate aminotransferase (AST), calcium
      and lipase were omitted from the electronic request form and could subsequently
      be ordered either by phone or a typed-in request. A reflex testing protocol was
      elaborated for reduction of creatine kinase (CK) and CK-MB analyses. All
      interventions were introduced with prior consultation with clinical staff and
      according to current guidelines. The reduction of test orders and costs in the
      post-intervention period was assessed. All data were retrieved retrospectively
      from the laboratory information system (LIS). RESULTS: Disappearance from the
      tick box request form resulted in a significant decrease in the number of
      requests for targeted tests in the post-intervention year, mostly affecting AST
      and fibrinogen (83% and 79% reduction of ordering, respectively), followed by a
      58% reduction in calcium orders, and 54% and 43% reductions in ESR and lipase
      requests, respectively. A substantial reduction in CK requests was also observed,
      while CK-MB requests almost disappeared. Annual cost savings that emerged from
      all implemented interventions were estimated to be 19,445?. CONCLUSION:
      Significant reduction in ordering of selected tests was achieved simply by
      limiting their availability in hospital computerized order entry (COE) system.
      The present data suggest that removal of laboratory tests from the electronic
      request form can be an effective tool for changing physicians' test ordering
      behavior.

PMID- 28495347
TI  - A web-based clinical decision support system for gestational diabetes: Automatic
      diet prescription and detection of insulin needs.
AB  - BACKGROUND: The growth of diabetes prevalence is causing an increasing demand in
      health care services which affects the clinicians' workload as medical resources
      do not grow at the same rate as the diabetic population. Decision support tools
      can help clinicians with the inspection of monitoring data, providing a
      preliminary analysis to ease their interpretation and reduce the evaluation time
      per patient. This paper presents Sinedie, a clinical decision support system
      designed to manage the treatment of patients with gestational diabetes. Sinedie
      aims to improve access to specialized healthcare assistance, to prevent patients
      from unnecessary displacements, to reduce the evaluation time per patient and to
      avoid gestational diabetes adverse outcomes. METHODS: A web-based telemedicine
      platform was designed to remotely evaluate patients allowing them to upload their
      glycaemia data at home directly from their glucose meter, as well as report other
      monitoring variables like ketonuria and compliance to dietary treatment.
      Glycaemia values, not tagged by patients, are automatically labelled with their
      associated meal by a classifier based on the Expectation Maximization clustering
      algorithm and a C4.5 decision tree learning algorithm. Two finite automata are
      combined to determine the patient's metabolic condition, which is analysed by a
      rule-based knowledge base to generate therapy adjustment recommendations. Diet
      recommendations are automatically prescribed and notified to the patients,
      whereas recommendations about insulin requirements are notified also to the
      physicians, who will decide if insulin needs to be prescribed. The system
      provides clinicians with a view where patients are prioritized according to their
      metabolic condition. A randomized controlled clinical trial was designed to
      evaluate the effectiveness and safety of Sinedie interventions versus standard
      care and its impact in the professionals' workload in terms of the clinician's
      time required per patient; number of face-to-face visits; frequency and duration
      of telematics reviews; patients' compliance to self-monitoring; and patients'
      satisfaction. RESULTS: Sinedie was clinically evaluated at "Parc Tauli University
      Hospital" in Spain during 17 months with the participation of 90 patients with
      gestational diabetes. Sinedie detected all situations that required a therapy
      adjustment and all the generated recommendations were safe. The time devoted by
      clinicians to patients' evaluation was reduced by 27.389% and face-to-face visits
      per patient were reduced by 88.556%. Patients reported to be highly satisfied
      with the system, considering it useful and trusting in being well controlled.
      There was no monitoring loss and, in average, patients measured their glycaemia
      3.890 times per day and sent their monitoring data every 3.477days. CONCLUSIONS:
      Sinedie generates safe advice about therapy adjustments, reduces the clinicians'
      workload and helps physicians to identify which patients need a more urgent or
      more exhaustive examination and those who present good metabolic control.
      Additionally, Sinedie saves patients unnecessary displacements which contributes
      to medical centres' waiting list reduction.

PMID- 28495348
TI  - Development of a tripolar model of technology acceptance: Hospital-based
      physicians' perspective on EHR.
AB  - BACKGROUND AND PURPOSE: In health care, information technologies (IT) hold a
      promise to harness an ever-increasing flow of health related information and
      bring significant benefits including improved quality of care, efficiency, and
      cost containment. One of the main tools for collecting and utilizing health data
      is the Electronic Health Record (EHR). EHRs implementation can face numerous
      barriers to acceptance including attitudes and perceptions of potential users,
      required effort attributed to their implementation and usage, and resistance to
      change. Various theories explicate different aspects of technology deployment,
      implementation, and acceptance. One of the common theories is the Technology
      Acceptance Model (TAM), which helps to study the implementation of different
      healthcare IT applications. The objectives of this study are: to understand the
      barriers of EHR implementation from the perspective of physicians; to identify
      major determinants of physicians' acceptance of technology; and develop a model
      that explains better how EHRs (and technologies in general) are accepted by
      physicians. METHODS: The proposed model derives from a cross-sectional survey of
      physicians selected through multi-stage cluster sampling from the hospitals of
      Yerevan, Armenia. The study team designed the survey instrument based on a
      literature review on barriers of EHR implementation. The analysis employed
      exploratory structural equation modeling (ESEM) with a robust weighted least
      squares (WLSMV) estimator for categorical indicators. The analysis progressed in
      two steps: appraisal of the measurement model and testing of the structural
      model. RESULTS: The derived model identifies the following factors as direct
      determinants of behavioral intention to use a novel technology: projected
      collective usefulness; personal innovativeness; patient influence; and resistance
      to change. Other factors (e.g., organizational change, professional
      relationships, administrative monitoring, organizational support and computer
      anxiety) exert their effects through projected collective usefulness, perceived
      usefulness, and perceived ease of use. The model reconciles individual-oriented
      and environment-oriented theoretical approaches and proposes a Tripolar Model of
      Technology Acceptance (TMTA), bringing together three key pillars of the
      healthcare: patients, practitioners, and provider organizations. The proposed
      TMTA explains 85% of variance of behavioral intention to use technology.
      CONCLUSIONS: The current study draws from the barriers of EHR implementation and
      identifies major determinants of technology acceptance among physicians. The
      study proposes TMTA as affording stronger explanative and predictive abilities
      for the health care system. TMTA paves a long overlooked gap in TAM and its
      descendants, which, in organizational settings, might distort construal of
      technology acceptance. It also explicates with greater depth the interdependence
      of different participants of the healthcare and complex interactions between
      healthcare and technologies.

PMID- 28495349
TI  - Factors that impact Patient Web Portal Readiness (PWPR) among the underserved.
AB  - OBJECTIVE: Healthcare organizations in the US are increasingly using Patient
      Portals as a means to provide patients with partial access to their health
      records and thereby comply with the 'meaningful use' of Health Information
      Technology policy issued by the US federal government. Patient portals are used
      to not only provide access to parts of the health records such as lab results but
      also offer services such as customized educational materials and appointment
      scheduling. While prior studies examining the adoption rates of these patient
      portals have not offered consistent findings, many of the studies have reported
      limited adoption and use [1] of patient portals, especially among the underserved
      population. This study explores the factors behind the reduced adoption rate of
      patient portals among the underserved by focusing on their Patient Web Portal
      Readiness (PWPR). DESIGN: The study empirically evaluates the impact of three
      important variables on PWPR among the underserved: (a) Personal Health
      Information Management (PHIM) activities, (b) patient attitude toward personal
      health record keeping; and (c) use of Internet for health information seeking.
      The study also incorporates three other factors: (d) access to Internet; (e)
      demographics; and (f) presence of chronic illness. MEASUREMENTS: Data were
      collected through a survey from 132 patients from the underserved population who
      visited 5 free clinics in the Northern Virginia area in the US. The paper-based
      survey was administered to the patients who visited these free clinics for care.
      RESULTS: The study findings show support for the hypotheses related to the impact
      of the two key factors - Personal Health Information Management (PHIM) activities
      and attitude toward personal health record keeping - on PWPR. The findings also
      indicate that the use of Internet for health information seeking has relatively
      more impact than patient's Internet access on PWPR. Overall, the findings imply
      the critical importance of complementary activities - e.g., PHIM activities,
      Internet-based health information seeking - to enhance PWPR among the underserved
      population.

PMID- 28495351
TI  - Electronic health record in the internal medicine clinic of a Brazilian
      university hospital: Expectations and satisfaction of physicians and patients.
AB  - PURPOSE: To evaluate the satisfaction and expectations of patients and physicians
      before and after the implementation of an electronic health record (EHR) in the
      outpatient clinic of a university hospital. METHODS: We conducted 389 interviews
      with patients and 151 with physicians before and after the implementation of a
      commercial EHR at the internal medicine clinic of Hospital das Clinicas of the
      Faculty of Medicine of the University of Sao Paulo (HC-FMUSP), Brazil. The
      physicians were identified by their connection to the outpatient clinic and
      categorized by their years since graduation: residents and preceptors (with 10
      years or less of graduation) or assistants (with more than 10 years of
      graduation). The answers to the questionnaire given by the physicians were
      classified as favorable or against the use of EHR, before and after the
      implementation of this system in this clinic, receiving 1 or 0 points,
      respectively. The sum of these points generated a multiple regression score to
      determine which factors contribute to the acceptance of EHR by physicians. We
      also did a third survey, after the EHR was routinely established in the
      outpatient clinic. RESULTS: The degree of patient satisfaction was the same
      before and after implementation, with more than 90% positive evaluations. They
      noted the use of the computer during the consultation and valued such use.
      Resident (younger) physicians had more positive expectations than assistants
      (older physicians) before EHR implementation. This optimism was reduced after
      implementation. In the third evaluation the use of EHR was higher among resident
      physicians. Resident physicians perceived and valued the EHR more and used it
      more. In 28 of the 57 questions on performance of clinical tasks, resident
      physicians found it easier to use EHR than assistant physicians with significant
      differences (p<0.05). When questioned specifically about EHR satisfaction,
      resident physicians responded "good" and "excellent" to a greater extent than
      assistant physicians (p=0.002). CONCLUSIONS: Our results reinforce the idea that
      the EHR introduction in a clinical setting should be preceded by careful planning
      to improve physician's adherence to the use of EHR. Patients do not seem to
      notice much difference to the quality of the consultation done using paper or
      EHR. It became clear after the third evaluation with the physicians that the
      younger (residents and some preceptors) perceived the advantages of the EHR more
      than the older physicians. Resident physicians use the EHR more and are more
      satisfied with it.

PMID- 28495350
TI  - Decaying relevance of clinical data towards future decisions in data-driven
      inpatient clinical order sets.
AB  - OBJECTIVE: Determine how varying longitudinal historical training data can impact
      prediction of future clinical decisions. Estimate the "decay rate" of clinical
      data source relevance. MATERIALS AND METHODS: We trained a clinical order
      recommender system, analogous to Netflix or Amazon's "Customers who bought A also
      bought B..." product recommenders, based on a tertiary academic hospital's
      structured electronic health record data. We used this system to predict future
      (2013) admission orders based on different subsets of historical training data
      (2009 through 2012), relative to existing human-authored order sets. RESULTS:
      Predicting future (2013) inpatient orders is more accurate with models trained on
      just one month of recent (2012) data than with 12 months of older (2009) data
      (ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10-10).
      Algorithmically learned models from even the older (2009) data was still more
      effective than existing human-authored order sets (ROC AUC 0.81, precision 16%
      recall 35%). Training with more longitudinal data (2009-2012) was no better than
      using only the most recent (2012) data, unless applying a decaying weighting
      scheme with a "half-life" of data relevance about 4 months. DISCUSSION: Clinical
      practice patterns (automatically) learned from electronic health record data can
      vary substantially across years. Gold standards for clinical decision support are
      elusive moving targets, reinforcing the need for automated methods that can adapt
      to evolving information. CONCLUSIONS AND RELEVANCM: Prioritizing small amounts of
      recent data is more effective than using larger amounts of older data towards
      future clinical predictions.

PMID- 28495352
TI  - Reliability of commercially available sleep and activity trackers with manual
      switch-to-sleep mode activation in free-living healthy individuals.
AB  - INTRODUCTION: Wearable health devices have become trendy among consumers, but it
      is not known whether they accurately measure sleep and physical activity
      parameters. To address this question, we have studied the measured data of two
      consumer-level activity monitors (Up Move Jawbone(r) (U) and Withings Pulse 02(r)
      (W)) and compared it with reference methods for sleep and activity recordings,
      namely the Bodymedia SenseWear Pro Armband(r) actigraph (SWA) and home
      polysomnography (H-PSG). METHODS: Twenty healthy patients were assessed at home,
      during sleep, with the four devices. An additional 24-h period of recording was
      then planned during which they wore the 2 trackers and the SWA. Physical activity
      and sleep parameters obtained with the 4 devices were analyzed. RESULTS:
      Significant correlations with H-PSG were obtained for total sleep time (TST) for
      all the devices: r=0.48 for W (p=0.04), r=0.63 for U (p=0.002), r=0.7 for SWA
      (p=0.0003). The best coefficient was obtained with SWA. Significant correlations
      were also obtained for time in bed (TIB) for U and SWA vs PSG (r=0.79 and r=0.76,
      p<0.0001 for both) but not for W (r=0.45, p=0.07). No significant correlations
      were obtained for deep sleep, light sleep, and sleep efficiency (SE) measurements
      with W, U and SWA. Sleep latency (SL) correlated with H-PSG only when measured
      against SWA (r=0.5, p=0.02). Physical activity assessment revealed significant
      correlations for U and W with SWA for step count (both r=0.95 and p<0.0001) and
      active energy expenditure (EE) (r=0.65 and 0.54; p=0.0006 and p<0.0001). Total EE
      was also correctly estimated (r=0.75 and 0.52; p<0.0001 and p=0.001). CONCLUSION:
      Sleep and activity monitors are only able to produce a limited set of reliable
      measurements, such as TST, step count, and active EE, with a preference for U
      which performs globally better. Despite the manual activation to sleep mode, U
      and W were not suitable for giving correct data such as sleep architecture, SE,
      and SL. In the future, to enhance accuracy of such monitors, researchers and
      providers have to collaborate to write algorithms based reliably on sleep
      physiology. It could avoid misleading the consumer.

PMID- 28495353
TI  - Identifying patient-related information problems: A study of information use by
      patient-care teams during morning rounds.
AB  - OBJECTIVE: This study identifies the types of patient-related information
      problems (PIPs) that patient-care teams encounter during morning rounds, and how
      those PIPs are identified and managed. PIPs are any issues related to patient
      information (e.g., wrong, missing, incomplete information) that affect the
      patient-care team's ability to perform their work. Not addressing PIPs can lead
      to workflow challenges, delayed patient-care decisions, and negative impacts to
      the patient. MATERIALS AND METHODS: We employed qualitative data collection
      methods by shadowing patient-care teams during 29 morning rounds resulting in
      155h of observation. We observed the interactions between the rounding physicians
      and other patient-care team members, including: nurses, consulting physicians,
      care coordinators, pharmacists, social workers, and therapists. RESULTS: This
      study resulted in identifying seven types of PIPs that occur during morning
      rounds. Additionally, the study presents the different ways that participants
      identified and managed the PIPs. DISCUSSION: We discuss the potential negative
      effects of PIPs on the patient-care workflow. We also discuss socio-technical
      recommendations for organizational policies and training, as well as electronic
      health record (EHR) design improvements that could help patient-care teams more
      effectively identify and manage PIPs. CONCLUSION: Hospital teams rely on
      accurate, available, and up-to-date information in order to make informed
      decisions on patient care. However, PIPs exist in EHR systems, paper documents,
      and verbal conversations. This study identifies a set of PIPs and how they are
      currently being identified and managed.

PMID- 28495354
TI  - Tafenoquine for malaria prophylaxis in adults: An integrated safety analysis.
AB  - BACKGROUND: Tafenoquine is a new prophylactic antimalarial drug. The current
      analysis presents an integrated safety assessment of the Tafenoquine Anticipated
      Clinical Regimen (Tafenoquine ACR) from 5 clinical trials, including 1 conducted
      in deployed military personnel and 4 in non-deployed residents, which also
      incorporated placebo and mefloquine comparator groups. METHODS: Adverse events
      (AEs) were coded according to the Medical Dictionary for Regulatory Activities
      (MedDRA(r), Version 15.0) and summarized. Among all subjects who had received the
      Tafenoquine ACR, safety findings were compared for subjects who were deployed
      military personnel from the Australian Defence Force (Deployed ADF) versus non
      deployed residents (Resident Non-ADF). RESULTS: The incidence of at least one AE
      was 80.6%, 64.1%, 67.6% and 94.9% in the mefloquine, placebo, tafenoquine
      Resident Non-ADF and tafenoquine Deployed ADF groups, respectively. The latter
      group had a higher incidence of AEs related to military deployment. AEs that
      occurred at >= 1% incidence in both tafenoquine sub-groups and at a higher
      frequency than placebo included diarrhea, nausea, vomiting, gastroenteritis,
      nasopharyngeal tract infections, and back/neck pain. CONCLUSIONS: Weekly
      administration of tafenoquine for up to six months increased the incidence of
      gastrointestinal AEs, certain infections, and back/neck pain, but not the overall
      incidence of AEs versus placebo. CLINICAL TRIAL REGISTRATION
      NUMBERS/CLINICALTRIALS. GOV IDENTIFIERS: NCT02491606; NCT02488980; NCT02488902.

PMID- 28495355
TI  - Tafenoquine is not neurotoxic following supertherapeutic dosing in rats.
AB  - BACKGROUND: Tafenoquine is a new drug for malaria prevention. The goal of the
      present work was to conduct a specific neurobehavioral study in rats with
      histopathological assessment of the brain. METHODS: The clinical, hematological,
      behavioral, motor activity, and neurohistopathologic changes induced by different
      dose levels of tafenoquine were evaluated following single super-therapeutic dose
      administration. Toxicokinetic data were generated to allow extrapolation to
      clinical exposures. RESULTS: At the highest dose (500 mg/kg), two animals (of 12)
      died. Surviving animals showed clinical signs of toxicity and had reduced body
      weight 7-8 days after dosing. Decreases in motor activity were observed on more
      than one occasion at doses > 9-fold higher than the clinical exposure. No
      statistically significant changes were observed for other behavioral endpoints.
      No neurohistopathological changes were noted. Changes in hematological and
      clinical pathology endpoints were observed at the lowest dose level (125 mg/kg).
      For context, the human dosing regimen is a 10 mg/kg load followed by 3.3 mg/kg
      weekly (in a 60 kg person). CONCLUSIONS: As in humans, adverse events other than
      neurotoxicity were dose-limiting for tafenoquine in rats. This raises the
      prospect that a new weekly prophylactic, without neurologic liability, may become
      available in the near future.

PMID- 28495356
TI  - Scleral topography analysed by optical coherence tomography.
AB  - PURPOSE: A detailed evaluation of the corneo-scleral-profile (CSP) is of
      particular relevance in soft and scleral lenses fitting. The aim of this study
      was to use optical coherence tomography (OCT) to analyse the profile of the
      limbal sclera and to evaluate the relationship between central corneal radii,
      corneal eccentricity and scleral radii. METHODS: Using OCT (Optos OCT/SLO;
      Dunfermline, Scotland, UK) the limbal scleral radii (SR) of 30 subjects (11M,
      19F; mean age 23.8+/-2.0SD years) were measured in eight meridians 45 degrees 
      apart. Central corneal radii (CR) and corneal eccentricity (CE) were evaluated
      using the Oculus Keratograph 4 (Oculus, Wetzlar, Germany). Differences between SR
      in the meridians and the associations between SR and corneal topography were
      assessed. RESULTS: Median SR measured along 45 degrees  (58.0; interquartile
      range, 46.8-84.8mm) was significantly (p<0.001) flatter than along 0 degrees 
      (30.7; 24.5-44.3mm), 135 degrees  (28.4; 24.9-30.9mm), 180 degrees  (23.40; 21.3
      25.4mm), 225 degrees  (25.8; 22.4-32.4mm), 270 degrees  (28.8; 25.3-33.1mm), 315
      degrees  (30.0; 25.0-36.9mm), and 90 degrees  (37.1; 29.1-43.4mm). In addition,
      the nasal SR along 0 degrees  were significant flatter than the temporal SR along
      180 degrees  (p<0.001). Central corneal radius in the flat meridian (7.83+/
      0.26mm) and in the steep meridian (7.65+/-0.26mm) did not correlate with SR
      (p=0.186 to 0.998). There was no statistically significant correlation between
      corneal eccentricity and scleral radii in each meridian (p=0.422). CONCLUSIONS:
      With the OCT device used in this study it was possible to measure scleral radii
      in eight different meridians. Scleral radii are independent of corneal topography
      and may provide additional data useful in fitting soft and scleral contact
      lenses.

PMID- 28495357
TI  - European survey on forensic applications of massively parallel sequencing.

PMID- 28495359
TI  - Gender differences in obstructive sleep apnoea, insomnia and restless legs
      syndrome in adults - What do we know? A clinical update.
AB  - Research in sleep medicine over the last decades has involved a broad variety of
      sleep disorders in both men and women. Gender differences have been identified in
      sleep physiology as well as in the three most common sleep disorders: obstructive
      sleep apnoea (OSA), insomnia and restless legs syndrome (RLS). However, research
      on gender differences in sleep medicine appears limited. This clinical review
      aims to give an updated overview of gender differences, in relation to
      prevalence, clinical presentation, treatment and quality of life in OSA, insomnia
      and RLS. Future research directions in the adult population will also be
      discussed.

PMID- 28495360
TI  - Fractures and Osteomalacia in a Patient Treated With Frequent Home Hemodialysis.
AB  - Bone deformities and fractures are common consequences of renal osteodystrophy in
      the dialysis population. Persistent hypophosphatemia may be observed with more
      frequent home hemodialysis regimens, but the specific effects on the skeleton are
      unknown. We present a patient with end-stage renal disease treated with frequent
      home hemodialysis who developed severe bone pain and multiple fractures,
      including a hip fracture and a tibia-fibula fracture complicated by nonunion,
      rendering her nonambulatory and wheelchair bound for more than a year. A bone
      biopsy revealed severe osteomalacia, likely secondary to chronic hypophosphatemia
      and hypocalcemia. Treatment changes included the addition of phosphate to the
      dialysate, a higher dialysate calcium concentration, and increased calcitriol
      dose. Several months later, the patient no longer required a wheelchair and was
      able to ambulate without pain. Repeat bone biopsy revealed marked improvements in
      bone mineralization and turnover parameters. Also, with increased dialysate
      phosphate and calcium concentrations, as well as increased calcitriol,
      circulating fibroblast growth factor 23 levels increased.

PMID- 28495358
TI  - Animal to human translational paradigms relevant for approach avoidance conflict
      decision making.
AB  - Avoidance behavior in clinical anxiety disorders is often a decision made in
      response to approach-avoidance conflict, resulting in a sacrifice of potential
      rewards to avoid potential negative affective consequences. Animal research has a
      long history of relying on paradigms related to approach-avoidance conflict to
      model anxiety-relevant behavior. This approach includes punishment-based
      conflict, exploratory, and social interaction tasks. There has been a recent
      surge of interest in the translation of paradigms from animal to human, in
      efforts to increase generalization of findings and support the development of
      more effective mental health treatments. This article briefly reviews animal
      tests related to approach-avoidance conflict and results from lesion and
      pharmacologic studies utilizing these tests. We then provide a description of
      translational human paradigms that have been developed to tap into related
      constructs, summarizing behavioral and neuroimaging findings. Similarities and
      differences in findings from analogous animal and human paradigms are discussed.
      Lastly, we highlight opportunities for future research and paradigm development
      that will support the clinical utility of this translational work.

PMID- 28495362
TI  - Editorial Comment.

PMID- 28495361
TI  - What lies in the near future for the treatment of rheumatoid arthritis?

PMID- 28495364
TI  - Moxifloxacin is an effective and safe candidate agent for tuberculosis treatment:
      a meta-analysis.
AB  - BACKGROUND: To evaluate the efficacy and safety of the introduction of
      moxifloxacin into the recommended regimen for tuberculosis (TB) treatment.
      METHODS: A meta-analysis was performed of nine eligible studies regarding the
      effect of moxifloxacin plus the recommended regimen compared to the recommended
      regimen alone for the treatment of TB. RESULTS: In the efficacy analysis, the
      overall odds ratio (OR) for sputum culture conversion was 1.895 (95% confidence
      interval (CI) 1.355-2.651, p=0.000), indicating that when moxifloxacin is
      combined with the recommended regimen, the rate of sputum culture conversion is
      elevated compared to the recommended regimen alone. The overall OR for recurrence
      was 0.516 (95% CI 0.342-0.920, p=0.022), suggesting that the introduction of
      moxifloxacin into the recommended regimen reduces TB relapse after treatment. In
      the safety analysis, the overall OR was estimated to be 1.001 (95% CI 0.855
      1.172, p=0.989), demonstrating that adding moxifloxacin to the recommended
      regimen does not cause more adverse events during TB treatment. CONCLUSIONS: This
      meta-analysis suggests that the introduction of moxifloxacin into the recommended
      regimen for the treatment of non-drug resistant TB improves the clinical outcome
      by elevating the culture conversion rate and reducing the recurrence rate.

PMID- 28495363
TI  - APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated
      degradation of the LDLR in vivo.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that
      post-transcriptionally regulates the levels of hepatic low-density lipoprotein
      receptors (LDLRs). PCSK9 binds to the extracellular domain of the LDLR, and the
      PCSK9-LDLR complex is internalized through canonical clathrin-dependent
      endocytosis and then delivered to lysosomes for degradation. The mechanism by
      which PCSK9 blocks recycling of the LDLR has not been fully defined. Previous
      reports showed that amyloid precursor-like protein 2 (APLP2) interacts with
      PCSK9, but its role in PCSK9-mediated LDLR degradation remains controversial.
      Here we found that amyloid precursor protein (APP), APLP2 and LDL receptor
      related protein 1 (LRP1) interact with PCSK9. To test whether any of these
      proteins are required for PCSK9-mediated LDLR degradation, we examined the
      effects of disrupting these proteins in mice. Infusion of PCSK9 into App-/-,
      Aplp2-/-, Aplp2-depleted App-/-, or liver-specific Lrp1-/- mice resulted in
      similar reductions in the levels of hepatic LDLR as seen in wild-type (WT) mice.
      Infusion of PCSK9 into WT mice also had no effect on the levels of hepatic APP,
      APLP2 or LRP1. Thus, APP, APLP2 and LRP1 are not required for PCSK9-mediated LDLR
      degradation and are not regulated by PCSK9 in vivo.

PMID- 28495365
TI  - The yin and yang of apolipoprotein CIII.

PMID- 28495366
TI  - Multimorbidity With HIV: Views of Community-Based People Living With HIV and
      Other Chronic Conditions.
AB  - People living with HIV (PLWH) experience an increase in chronic conditions with
      aging, but little is known about experiences of living with multimorbidity with
      HIV. Because early palliative care services may improve well-being for
      individuals with multimorbidity, we planned to test an intervention to provide
      these services to community-dwelling PLWH with other chronic conditions. To
      tailor our intervention to the target population, we conducted four focus groups
      (n = 22) that elicited health-related needs, experiences, and views regarding
      palliative and other health services. We identified four themes related to
      patients' needs and experiences: views of HIV as background to other chronic
      conditions, challenges managing medications and provider interactions, concerns
      about coping with future health needs, and persistence of HIV stigma. In
      addressing multimorbidity with HIV, providers and patients may benefit from
      enhanced attention to communication when crossing specialty areas and from
      additional support to decrease stressors associated with HIV stigma.

PMID- 28495367
TI  - In vivo effects of Allium cepa L. on the selected gut microflora and intestinal
      histomorphology in broiler.
AB  - The experiment was conducted to evaluate the effect of onion (Allium cepa L.,) on
      the performance, gut microflora and intestinal histomorphology of broiler chicks.
      Three hundred and twenty day old broiler chicks (Ross) were randomly divided into
      four groups as A, B, C and D. Group A served as control without any
      supplementation, group B, C and D was supplemented with onion powder at the rate
      of 1.5, 2 and 2.5g/kg of feed respectively. Supplementation of onion
      significantly (P<0.05) increased weight gain and feed consumption.
      Supplementation of onion showed a significant (P<0.05) reduction in the
      population of E. coli and increased significantly Lactobacillus and Streptococcus
      species. Onion supplementation significantly (P<0.05) increased the morphometry
      of length, width, crypt depth and surface area of the villus in duodenum, jejunum
      and ileum of the small intestine. In conclusion, onion supplementation in broiler
      produced a positive effect on performance, gut microflora and intestinal
      histomorphology.

PMID- 28495368
TI  - The dynamic programming high-order Dynamic Bayesian Networks learning for
      identifying effective connectivity in human brain from fMRI.
AB  - BACKGROUND: Determination of effective connectivity (EC) among brain regions
      using fMRI is helpful in understanding the underlying neural mechanisms. Dynamic
      Bayesian Networks (DBNs) are an appropriate class of probabilistic graphical
      temporal-models that have been used in past to model EC from fMRI, specifically
      order-one. NEW-METHOD: High-order DBNs (HO-DBNs) have still not been explored for
      fMRI data. A fundamental problem faced in the structure-learning of HO-DBN is
      high computational-burden and low accuracy by the existing heuristic search
      techniques used for EC detection from fMRI. In this paper, we propose using
      dynamic programming (DP) principle along with integration of properties of
      scoring-function in a way to reduce search space for structure-learning of HO
      DBNs and finally, for identifying EC from fMRI which has not been done yet to the
      best of our knowledge. The proposed exact search-&-score learning approach HO-DBN
      DP is an extension of the technique which was originally devised for learning a
      BN's structure from static data (Singh and Moore, 2005). RESULTS: The
      effectiveness in structure-learning is shown on synthetic fMRI dataset. The
      algorithm reaches globally-optimal solution in appreciably reduced time
      complexity than the static counterpart due to integration of properties. The
      proof of optimality is provided. COMPARISON: The results demonstrate that HO-DBN
      DP is comparably more accurate and faster than currently used structure-learning
      algorithms used for identifying EC from fMRI. The real data EC from HO-DBN-DP
      shows consistency with previous literature than the classical Granger Causality
      method. CONCLUSION: Hence, the DP algorithm can be employed for reliable EC
      estimates from experimental fMRI data.

PMID- 28495369
TI  - Group-level spatio-temporal pattern recovery in MEG decoding using multi-task
      joint feature learning.
AB  - BACKGROUND: The use of machine learning models to discriminate between patterns
      of neural activity has become in recent years a standard analysis approach in
      neuroimaging studies. Whenever these models are linear, the estimated parameters
      can be visualized in the form of brain maps which can aid in understanding how
      brain activity in space and time underlies a cognitive function. However, the
      recovered brain maps often suffer from lack of interpretability, especially in
      group analysis of multi-subject data. NEW METHOD: To facilitate the application
      of brain decoding in group-level analysis, we present an application of multi
      task joint feature learning for group-level multivariate pattern recovery in
      single-trial magnetoencephalography (MEG) decoding. The proposed method allows
      for recovering sparse yet consistent patterns across different subjects, and
      therefore enhances the interpretability of the decoding model. RESULTS: Our
      experimental results demonstrate that the mutli-task joint feature learning
      framework is capable of recovering more meaningful patterns of varying spatio
      temporally distributed brain activity across individuals while still maintaining
      excellent generalization performance. COMPARISON WITH EXISTING METHODS: We
      compare the performance of the multi-task joint feature learning in terms of
      generalization, reproducibility, and quality of pattern recovery against
      traditional single-subject and pooling approaches on both simulated and real MEG
      datasets. CONCLUSIONS: These results can facilitate the usage of brain decoding
      for the characterization of fine-level distinctive patterns in group-level
      inference. Considering the importance of group-level analysis, the proposed
      approach can provide a methodological shift towards more interpretable brain
      decoding models.

PMID- 28495371
TI  - Detecting joint pausiness in parallel spike trains.
AB  - BACKGROUND: Transient periods with reduced neuronal discharge - called 'pauses' -
      have recently gained increasing attention. In dopamine neurons, pauses are
      considered important teaching signals, encoding negative reward prediction
      errors. Particularly simultaneous pauses are likely to have increased impact on
      information processing. COMPARISON WITH EXISTING METHODS: Available methods for
      detecting joint pausing analyze temporal overlap of pauses across spike trains.
      Such techniques are threshold dependent and can fail to identify joint pauses
      that are easily detectable by eye, particularly in spike trains with different
      firing rates. NEW METHOD: We introduce a new statistic called pausiness that
      measures the degree of synchronous pausing in spike train pairs and avoids
      threshold-dependent identification of specific pauses. A new graphic termed the
      cross-pauseogram compares the joint pausiness of two spike trains with its time
      shifted analogue, such that a (pausiness) peak indicates joint pausing. When
      assessing significance of pausiness peaks, we use a stochastic model with
      synchronous spikes to disentangle joint pausiness arising from synchronous spikes
      from additional 'joint excess pausiness' (JEP). Parameter estimates are obtained
      from auto- and cross-correlograms, and statistical significance is assessed by
      comparison to simulated cross-pauseograms. RESULTS: Our new method was applied to
      dopamine neuron pairs recorded in the ventral tegmental area of awake behaving
      mice. Significant JEP was detected in about 20% of the pairs. CONCLUSION: Given
      the neurophysiological importance of pauses and the fact that neurons integrate
      multiple inputs, our findings suggest that the analysis of JEP can reveal
      interesting aspects in the activity of simultaneously recorded neurons.

PMID- 28495370
TI  - An optimized method for enumerating CNS derived memory B cells during viral
      induced inflammation.
AB  - BACKGROUND: CNS inflammation resulting from infection, injury, or
      neurodegeneration leads to accumulation of diverse B cell subsets. Although
      antibody secreting cells (ASC) within the inflamed CNS have been extensively
      examined, memory B cell (Bmem) characterization has been limited as they do not
      secrete antibody without stimulation. Moreover, unlike human Bmem, reliable
      surface markers for murine Bmem remain elusive. NEW METHOD: Using a viral
      encephalomyelitis model we developed a modified limiting dilution in vitro
      stimulation assay to convert CNS-derived virus specific Bmem into ASC. COMPARISON
      WITH EXISTING METHODS: Stimulation methods established for lymphoid tissue cells
      using prolonged stimulation with viral lysate resulted in substantial ASC loss
      and minimal Bmem to ASC conversion of CNS-derived cells. By varying stimulation
      duration, TLR activators, and culture supplements, we achieved optimal conversion
      by culturing cells with TLR7/8 agonist R848 in the presence of feeder cells for
      2days. RESULTS: Flow cytometry markers CD38 and CD73 characterizing murine Bmem
      from lymphoid tissue showed more diverse expression patterns on corresponding CNS
      derived B cell subsets. Using the optimized TLR7/8 stimulation protocol, we
      compared virus-specific IgG Bmem versus pre-existing ASC within the brain and
      spinal cord. Increasing Bmem frequencies during chronic infection mirrored
      kinetics of ASC. However, despite initially similar Bmem and ASC accumulation,
      Bmem prevailed in the brain, but were lower than ASC in the spinal cord during
      persistence. CONCLUSION: Simultaneous enumeration of antigen-specific Bmem and
      ASC using the Bmem assay optimized for CNS-derived cells enables characterization
      of temporal changes during microbial or auto-antigen induced neuroinflammation.

PMID- 28495372
TI  - Learning to recognize rat social behavior: Novel dataset and cross-dataset
      application.
AB  - BACKGROUND: Social behavior is an important aspect of rodent models. Automated
      measuring tools that make use of video analysis and machine learning are an
      increasingly attractive alternative to manual annotation. Because machine
      learning-based methods need to be trained, it is important that they are
      validated using data from different experiment settings. NEW METHOD: To develop
      and validate automated measuring tools, there is a need for annotated rodent
      interaction datasets. Currently, the availability of such datasets is limited to
      two mouse datasets. We introduce the first, publicly available rat social
      interaction dataset, RatSI. RESULTS: We demonstrate the practical value of the
      novel dataset by using it as the training set for a rat interaction recognition
      method. We show that behavior variations induced by the experiment setting can
      lead to reduced performance, which illustrates the importance of cross-dataset
      validation. Consequently, we add a simple adaptation step to our method and
      improve the recognition performance. COMPARISON WITH EXISTING METHODS: Most
      existing methods are trained and evaluated in one experimental setting, which
      limits the predictive power of the evaluation to that particular setting. We
      demonstrate that cross-dataset experiments provide more insight in the
      performance of classifiers. CONCLUSIONS: With our novel, public dataset we
      encourage the development and validation of automated recognition methods. We are
      convinced that cross-dataset validation enhances our understanding of rodent
      interactions and facilitates the development of more sophisticated recognition
      methods. Combining them with adaptation techniques may enable us to apply
      automated recognition methods to a variety of animals and experiment settings.

PMID- 28495373
TI  - Amyloid-beta neurotoxicity and clearance are both regulated by glial group II
      metabotropic glutamate receptors.
AB  - Astrocytes are now fully endorsed as key players in CNS functionality and
      plasticity. We recently showed that metabotropic glutamate receptor 3 (mGlu3R)
      activation by LY379268 promotes non-amyloidogenic cleavage of amyloid precursor
      protein (APP) in cultured astrocytes, leading to increased release of
      neuroprotective sAPPalpha. Furthermore, mGlu3R expression is reduced in
      hippocampal astrocytes from PDAPP-J20 mice, suggesting a role for these receptors
      in Alzheimer's disease. The present study enquires into the role of astroglial
      derived neurotrophins induced by mGlu3R activation in neurotoxicity triggered by
      amyloid beta (Abeta). Conditioned medium from LY379268-treated astrocytes
      protected hippocampal neurons from Abeta-induced cell death. Immunodepletion of
      sAPPalpha from the conditioned medium prevented its protective effect. LY379268
      induced brain-derived neurotrophic factor (BDNF) expression in astrocytes, and
      neutralizing BDNF from conditioned medium also prevented its neuroprotective
      effect on Abeta neurotoxicity. LY379268 was also able to decrease Abeta-induced
      neuron death by acting directly on neuronal mGlu3R. On the other hand, LY379268
      increased Abeta uptake in astrocytes and microglia. Indeed, and more importantly,
      a reduction in Abeta-induced neuron death was observed when co-cultured with
      LY379268-pretreated astrocytes, suggesting a link between neuroprotection and
      increased glial phagocytic activity. Altogether, these results indicate a double
      function for glial mGlu3R activation against Abeta neurotoxicity: (i) it
      increases the release of protective neurotrophins such as sAPPalpha and BDNF, and
      (ii) it induces amyloid removal from extracellular space by glia-mediated
      phagocytosis.

PMID- 28495374
TI  - Metyrapone prevents brain damage induced by status epilepticus in the rat lithium
      pilocarpine model.
AB  - The status epilepticus (SE) induced by lithium-pilocarpine is a well
      characterized rodent model of the human temporal lobe epilepsy (TLE) which is
      accompanied by severe brain damage. Stress and glucocorticoids markedly
      contribute to exacerbate neuronal damage induced by seizures but the underlying
      mechanisms are poorly understood. Herein we sought to investigate whether a
      single administration of metyrapone (150 mg/kg, i.p.), an 11beta-hydroxylase
      inhibitor, enzyme involved in the peripheral and central synthesis of
      corticosteroids, had neuroprotective properties in this model. Two experiments
      were carried out. In exp. 1, metyrapone was administered 3 h before pilocarpine
      injection whereas in exp. 2, metyrapone administration took place at the onset of
      the SE. In both experiments, 3 days after the insult, brain metabolism was
      assessed by in vivo 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission
      tomography (PET). Brains were processed for analyses of markers of hippocampal
      integrity (Nissl staining), neurodegeneration (Fluoro-Jade C), astrogliosis
      (glial fibrillary acidic protein (GFAP) immunohistochemistry) and, for a marker
      of activated microglia by in vitro autoradiography with the TSPO (18 kDa
      translocator protein) radioligand [18F]GE180. The SE resulted in a consistent
      hypometabolism in hippocampus, cortex and striatum and neuronal damage,
      hippocampal neurodegeneration, neuronal death and gliosis. Interestingly,
      metyrapone had neuroprotective effects when administered before, but not after
      the insult. In summary, we conclude that metyrapone administration prior but not
      after the SE protected from brain damage induced by SE in the lithium-pilocarpine
      model. Therefore, it seems that the effect of metyrapone is preventive in nature
      and likely related to its antiseizure properties.

PMID- 28495375
TI  - Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl
      CoA ligase in the citric acid cycle.
AB  - Methylene blue (MB), a potential neuroprotective agent, is efficient in various
      neurodegenerative disease models. Beneficial effects of MB have been attributed
      to improvements in mitochondrial functions. Substrate-level phosphorylation (SLP)
      results in the production of ATP independent from the ATP synthase (ATP-ase). In
      energetically compromised mitochondria, ATP produced by SLP can prevent the
      reversal of the adenine nucleotide translocase and thus the hydrolysis of
      glycolytic ATP. The aim of the present study was to investigate the effect of MB
      on mitochondrial SLP catalysed by succinyl-CoA ligase. Measurements were carried
      out on isolated guinea pig cortical mitochondria respiring on alpha
      ketoglutarate, glutamate, malate or succinate. The mitochondrial functions and
      parameters like ATP synthesis, oxygen consumption, membrane potential, and
      NAD(P)H level were followed online, in parallel with the redox state of MB. SLP
      mediated ATP synthesis was measured in the presence of inhibitors for ATP-ase and
      adenylate kinase. In the presence of the ATP-ase inhibitor oligomycin MB
      stimulated respiration with all of the respiratory substrates. However, the rate
      of ATP synthesis increased only with substrates alpha-ketoglutarate and glutamate
      (forming succinyl-CoA). MB efficiently stimulated SLP and restored the membrane
      potential in mitochondria also with the combined inhibition of Complex I and ATP
      synthase. ATP formed by SLP alleviated the energetic insufficiency generated by
      the lack of oxidative phosphorylation. Thus, the MB-mediated stimulation of SLP
      might be important in maintaining the energetic competence of mitochondria and in
      preventing the mitochondrial hydrolysis of glycolytic ATP. The mitochondrial
      effects of MB are explained by the ability to accept electrons from reducing
      equivalents and transfer them to cytochrome c bypassing the respiratory Complexes
      I and III.

PMID- 28495376
TI  - GABAA receptor positive allosteric modulators modify the abuse-related behavioral
      and neurochemical effects of methamphetamine in rhesus monkeys.
AB  - GABAA receptor positive allosteric modulators (GABAA receptor modulators) are
      commonly used for the treatment of insomnia. Nevertheless, the effects of these
      compounds on psychostimulant-induced sleep impairment are poorly understood.
      Because GABAA receptor modulators have been shown to decrease the abuse-related
      effects of psychostimulants, the aim of the present study was to evaluate the
      effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0
      mg/kg), two GABAA receptor modulators, on the behavioral neuropharmacology of
      methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general
      daytime activity were evaluated with Actiwatch monitors. Methamphetamine self
      administration (0.03 mg/kg/inf) was evaluated during morning sessions.
      Methamphetamine-induced dopamine overflow was assessed through in vivo
      microdialysis targeting the nucleus accumbens. Nighttime treatment with either
      temazepam or eszopiclone was ineffective in improving sleep-like measures
      disrupted by methamphetamine self-administration. Acute pretreatment with a low
      dose of temazepam before self-administration sessions increased methamphetamine
      self-administration without affecting normal daytime home-cage activity. At a
      high dose, acute temazepam pretreatment decreased methamphetamine self
      administration and attenuated methamphetamine-induced increases in dopamine in
      the nucleus accumbens, without decreasing general daytime activity. Acute
      eszopiclone treatment exerted no effects on methamphetamine intake or drug
      induced increases in dopamine. Our study suggests that treatments based on GABAA
      receptor modulators are not effective for the treatment of sleep disruption in
      the context of psychostimulant use. In addition, distinct GABAA receptor
      modulators differentially modulated the abuse-related effects of methamphetamine,
      with acute treatment with the high efficacy GABAA receptor modulator temazepam
      decreasing the behavioral and neurochemical effects of methamphetamine.

PMID- 28495377
TI  - Assembling a supercapacitor electrode with dual metal oxides and activated carbon
      using a liquid phase plasma.
AB  - Developing supercapacitor electrodes at an affordable cost while improving their
      energy and/or power density values is still a challenging task. This study
      introduced a recipe which assembled a novel electrode composite using a liquid
      phase plasma that was applied to a reactant solution containing an activated
      carbon (AC) powder with dual metal precursors of iron and manganese. A comparison
      was made between the composites doped with single and dual metal components as
      well as among those synthesized under different precursor concentrations and
      plasma durations. The results showed that increasing the precursor concentration
      and plasma duration raised the content of both metal oxides in the composites,
      whereas the deposition conditions were more favorable to iron oxide than
      manganese oxide, due to its higher standard potential. The composite treated with
      the longest plasma duration and highest manganese concentration was superior to
      the others in terms of cyclic stability and equivalent series resistance. In
      addition, the new composite selected out of them showed better electrochemical
      performance than the raw AC material only and even two types of single metal
      based composites, owing largely to the synergistic effect of the two metal
      oxides. Therefore, the proposed methodology can be used to modify existing and
      future composite electrodes to improve their performance with relatively cheap
      host and guest materials.

PMID- 28495378
TI  - Performance of biomorphic Silicon Carbide as particulate filter in diesel
      boilers.
AB  - Biomorphic Silicon Carbide (bioSiC) is a novel porous ceramic material with
      excellent mechanical and thermal properties. Previous studies have demonstrated
      that it may be a good candidate for its use as particle filter media of exhaust
      gases at medium or high temperature. In order to determine the filtration
      efficiency of biomorphic Silicon Carbide, and its adequacy as substrate for
      diesel particulate filters, different bioSiC-samples have been tested in the flue
      gases of a diesel boiler. For this purpose, an experimental facility to extract a
      fraction of the boiler exhaust flow and filter it under controlled conditions has
      been designed and built. Several filter samples with different microstructures,
      obtained from different precursors, have been tested in this bench. The
      experimental campaign was focused on the measurement of the number and size of
      particles before and after placing the samples. Results show that the initial
      efficiency of filters made from natural precursors is severely determined by the
      cutting direction and associated microstructure. In biomorphic Silicon Carbide
      derived from radially cut wood, the initial efficiency of the filter is higher
      than 95%. Nevertheless, when the cut of the wood is axial, the efficiency depends
      on the pore size and the permeability, reaching in some cases values in the range
      70-90%. In this case, the presence of macropores in some of the samples reduces
      their efficiency as particle traps. In continuous operation, the accumulation of
      particles within the porous media leads to the formation of a soot cake, which
      improves the efficiency except in the case when extra-large pores exist. For all
      the samples, after a few operation cycles, capture efficiency was higher than
      95%. These experimental results show the potential for developing filters for
      diesel boilers based on biomorphic Silicon Carbide.

PMID- 28495379
TI  - Transthoracic Echocardiography for Diagnosing Pulmonary Embolism: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: Pulmonary embolism (PE) is a common diagnosis with significant
      mortality if not appropriately treated. The use of transthoracic echocardiography
      in patients with PE is common; however, its diagnostic capabilities in this use
      are unclear. With the increased use of ultrasonography in medical settings, it is
      important to understand the strengths and limitations of echocardiography for the
      diagnosis of PE. METHODS: We conducted a systematic review of PubMed, CINAHL, and
      EMBASE through 2016 for articles assessing the diagnostic accuracy of
      transthoracic echocardiography for PE. Two authors independently abstracted
      relevant data from the studies. We assessed quality using the QUADAS-2 tool for
      diagnostic studies. RESULTS: Undefined "right heart strain" was the most common
      sign used, and it had a sensitivity of 53% (95% CI, 45%-61%) and a specificity of
      83% (95% CI, 74%-90%). Eleven other distinct signs were identified: ventricle
      size ratio, abnormal septal motion, tricuspid regurgitation, 60/60 sign,
      McConnell's sign, right heart thrombus, right ventricle hypokinesis, pulmonary
      hypertension, right ventricular end-diastolic diameter, tricuspid annular plane
      systolic excursion, and right ventricular systolic pressure. CONCLUSIONS: Studies
      show a consistently high specificity and low sensitivity for echocardiography in
      the diagnosis of PE, making it potentially adequate as a rule-in test at the
      bedside in critical care settings such as the emergency department and intensive
      care unit for patients with a suspicion of PE, especially those unable to get
      other confirmatory studies. Future research may continue to clarify the role of
      bedside echocardiography in conjunction with other tests and imaging in the
      overall management of PE.

PMID- 28495380
TI  - Outcomes associated with antibiotic regimens for treatment of Mycobacterium
      abscessus in cystic fibrosis patients.
AB  - BACKGROUND: Mycobacterium abscessus infection is associated with declining lung
      function in cystic fibrosis (CF), but there is little evidence on clinical
      efficacy to guide treatment. METHODS: Retrospective review of 37 CF patients
      treated for M. abscessus respiratory infection at a single center from 2006 to
      2014. Outcomes included change in FEV1 at 30, 60, 90, 180, and 365days after
      treatment and clearance of M. abscessus from sputum cultures. RESULTS: Lung
      function was significantly improved after 30 and 60days of treatment, but not at
      later time points. Gains were inversely related to starting lung function.
      Antibiotic choices did not influence outcomes except for greater clearance with
      clarithromycin. CONCLUSIONS: Treatment of M. abscessus resulted in short term
      improvement in lung function that is inversely related to pre-treatment FEV1.

PMID- 28495381
TI  - A fragment-based approach leading to the discovery of a novel binding site and
      the selective CK2 inhibitor CAM4066.
AB  - Recently we reported the discovery of a potent and selective CK2alpha inhibitor
      CAM4066. This compound inhibits CK2 activity by exploiting a pocket located
      outside the ATP binding site (alphaD pocket). Here we describe in detail the
      journey that led to the discovery of CAM4066 using the challenging fragment
      linking strategy. Specifically, we aimed to develop inhibitors by linking a high
      affinity fragment anchored in the alphaD site to a weakly binding warhead
      fragment occupying the ATP site. Moreover, we describe the remarkable impact that
      molecular modelling had on the development of this novel chemical tool. The work
      described herein shows potential for the development of a novel class of CK2
      inhibitors.

PMID- 28495382
TI  - Synthesis and structure-activity relationship of teixobactin analogues via
      convergent Ser ligation.
AB  - Convergent Ser/Thr ligation has been used to prepare a series of teixobactin
      analogues (28 in total) to establish a structure-activity relationship of
      teixobactin. anti-bacterial evaluations of these synthetic analogues have
      revealed the critical amino acid residues and the sites tolerable of
      modifications. These studies will shed lights on the further development of
      teixobactin analogues with improved antibacterial activities.

PMID- 28495383
TI  - Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential
      anticancer agent: Synthesis and evaluation.
AB  - With the rising incidences of cancer cases, the quest for new metal based
      anticancer drugs has led to extensive research in cancer biology. Zinc complexes
      of amino acid residue side chains are well recognized for hydrolysis of
      phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II)
      complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp)2
      has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen
      (Trp)2 was synthesized in ~70% yield and its DNA binding potential was evaluated
      through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The
      decrease in intensity of the positive and negative bands of CT-DNA at 278nm and
      240nm, respectively demonstrated an effective unwinding of the DNA helix with
      loss of helicity. The complex was identified as an antiproliferative agent
      against U-87MG cells with 5 fold increase in apoptosis with respect to control
      (2h post incubation, IC50 25uM). Electrophoresis and comet assay studies
      exhibited an increase in DNA breakage after treatment with complex while caspase
      3/beta-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87
      MG cells after triggering DNA damage. In vivo tumor specificity of the developed
      ligand was validated after radiocomplexation with 99mTc (>98% radiochemical yield
      and specific activity of 2.56GBq/umol). Avid tumor/muscle ratio of >6 was
      depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model
      nude mice.

PMID- 28495384
TI  - Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.
AB  - Neglected tropical diseases (NTDs) are a group of diseases that, besides
      prevailing in poverty conditions, contribute to the maintenance of social
      inequality, being a strong barrier to a country development. Schistosomiasis, a
      NTD, is a tropical and subtropical disease caused by the trematode Schistosoma
      mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum
      (China, Indonesia, the Philippines), mekongi (several districts of Cambodia and
      the Lao People's Democratic Republic), intercalatum and guianensis (areas of
      tropical rainforests in Central Africa) and hematobium (Middle East Africa,
      Corsica, France) whose adult forms inhabit the mesenteric vessels of the host,
      while the intermediate forms are found in the aquatic gastropod snails of the
      genus Biomphalaria. Currently, praziquantel (PZQ) is the first line drug chosen
      for the treatment of schistosomiasis according to the World Health Organization
      (WHO) Model List of Essential Medicines, 2015. PZQ chemotherapy is considered to
      be the most important development for decades in the treatment of
      schistosomiasis. Beside the PZQ, oxamniquine (OXA) has been first described in
      1969 and launched in Brazil by Pfizer under the name of Mansil(r) for oral
      administration. It has a lower cost when compared to PZQ, being active in the
      intestinal and hepatosplenic infections caused exclusively by S. mansoni, single
      species in Brazil. Both PZQ and OXA have limitations, as low efficacy in the
      treatment of acute schistosomiasis, low activity against S. mansoni in immature
      stages and resistance or tolerance, which is the reason why further research are
      still necessary for the development of a second generation of antischistosomal
      drugs. For the development of new PZQ analogs, three main strategies can be
      adopted: (a) synthesis and evaluation of PZQ analogues; (b) rational design of
      new pharmacophores; (c) discovery of new active compounds from screening programs
      on a large scale. Such (b) approach is difficult as the target of PZQ still
      unknown, the synthesis of new active analogues is possible from delineation of
      structure-activity relationships for PZQ. Thus, we proposed for a review article
      an accurate analysis of PZQ and OXA medicinal properties and uses, focusing on
      the pharmacochemical aspects of both drugs through 178 bibliographic references.
      The mechanisms of action will be discussed, with the latest information available
      in the literature (for the first time in the case of the oxamniquine). Cases of
      resistance are also discussed. As both drugs are available as a racemic mixture
      the biological impact of their stereochemistry to activity and side effects are
      reviewed. The results obtained for the combination of PZQ and artemisinin
      derivatives against immature worms are also introduced in the discussion. Using
      the information about more than 200 PZQ new derivatives synthetized during almost
      35years since its discovery, a deep structure-activity relationship (SAR) is also
      proposed in this study.

PMID- 28495385
TI  - Derivatives of caffeic acid, a natural antioxidant, as the basis for the
      discovery of novel nonpeptidic neurotrophic agents.
AB  - Neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease,
      threaten the lives of millions of people and the number of affected patients is
      constantly growing with the increase of the aging population. Small molecule
      neurotrophic agents represent promising therapeutics for the pharmacological
      management of neurodegenerative diseases. In this study, a series of caffeic acid
      amide analogues with variable alkyl chain lengths, including ACAF3 (C3), ACAF4
      (C4), ACAF6 (C6), ACAF8 (C8) and ACAF12 (C12) were synthesized and their
      neurotrophic activity was examined by different methods in PC12 neuronal cells.
      We found that all caffeic acid amide derivatives significantly increased survival
      in PC12 neuronal cells in serum-deprived conditions at 25MUM, as measured by the
      MTT assay. ACAF4, ACAF6 and ACAF8 at 5uM also significantly enhanced the effect
      of nerve growth factor (NGF) in inducing neurite outgrowth, a sign of neuronal
      differentiation. The neurotrophic effects of amide derivatives did not seem to be
      mediated by direct activation of tropomyosin receptor kinase A (TrkA) receptor,
      since K252a, a potent TrkA antagonist, did not block the neuronal survival
      enhancement effect. Similarly, the active compounds did not activate TrkA as
      measured by immunoblotting with anti-phosphoTrkA antibody. We also examined the
      effect of amide derivatives on signaling pathways involved in survival and
      differentiation by immunoblotting. ACAF4 and ACAF12 induced ERK1/2
      phosphorylation in PC12 cells at 5 and 25uM, while ACAF12 was also able to
      significantly increase AKT phosphorylation at 5 and 25uM. Molecular docking
      studies indicated that compared to the parental compound caffeic acid, ACAF12
      exhibited higher binding energy with phosphoinositide 3-kinase (PI3K) as a
      putative molecular target. Based on Lipinski's rule of five, all of the compounds
      obeyed three molecular descriptors (HBD, HBA and MM) in drug-likeness test. Taken
      together, these findings show for the first time that caffeic amides possess
      strong neurotrophic effects exerted via modulation of ERK1/2 and AKT signaling
      pathways presumably by activation of PI3K and thus represent promising agents for
      the discovery of neurotrophic compounds for management of neurodegenerative
      diseases.

PMID- 28495386
TI  - Development of molecular tools based on the dopamine D3 receptor ligand FAUC 329
      showing inhibiting effects on drug and food maintained behavior.
AB  - Dopamine D3 receptor-mediated networks have been associated with a wide range of
      neuropsychiatric diseases, drug addiction and food maintained behavior, which
      makes D3 a highly promising biological target. The previously described dopamine
      D3 receptor ligand FAUC 329 (1) showed protective effects against dopamine
      depletion in a MPTP mouse model of Parkinson's disease. We used the radioligand
      [18F]2, a [18F]fluoroethoxy substituted analog of the lead compound 1 as a
      molecular tool for visualization of D3-rich brain regions including the islands
      of Calleja. Furthermore, structural modifications are reported leading to the
      pyrimidylpiperazine derivatives 3 and 9 displaying superior subtype selectivity
      and preference over serotonergic receptors. Evaluation of the lead compound 1 on
      cocaine-seeking behavior in non-human primates showed a substantial reduction in
      cocaine self-administration behavior and food intake.

PMID- 28495387
TI  - Meta-analysis of serum non-high-density lipoprotein cholesterol and risk of
      coronary heart disease in the general population.
AB  - BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) has been
      proposed an independent risk factor for coronary heart disease (CHD). However,
      the magnitude of this association in the general population varied considerably.
      OBJECTIVE: To investigate the association of baseline non-HDL-C level with CHD
      risk in the general population by conducting a meta-analysis. METHODS: A
      comprehensive literature search was performed in the Pubmed and Embase until
      January 2017. Prospective observational studies that investigated the association
      between baseline non-HDL-C level and CHD risk in the general population were
      included. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI)
      were calculated for the highest vs. the lowest non-HDL-C category. RESULTS: Seven
      articles with 9 independent prospective studies involving 448,732 individuals
      were included. Meta-analysis showed that individuals with the highest non-HDL-C
      level at baseline were associated with greater risk of CHD (RR 1.79; 95% CI 1.68
      1.91) than those in the lowest non-HDL-C level category. Subgroup analysis
      suggested that the risk of CHD seemed more pronounced among men (HR 1.98; 95% CI
      1.70-2.30) than among women (HR 1.63; 95% CI 1.35-1.96). CONCLUSIONS: Higher
      baseline non-HDL-C level is associated with increased risk of CHD in the general
      population. This risk seems more pronounced in men than in women. However, gender
      difference in non-HDL-C level associated with CHD risk should be verified by more
      well-designed prospective studies.

PMID- 28495388
TI  - Recognizing and differentiating uncommon body fluids: Considerations and tools
      for a proper practical approach.
AB  - Clinical laboratories are regularly requested to inspect uncommon body fluids
      obtained from patients because clinicians are uncertain as to the origin of the
      collected material. They may need this information for the actual diagnosis, to
      confirm a supposition, or for guiding treatment and invasive operations like
      draining and puncturing. Often there is also a need to know more precisely what
      is going on in the cavity that gave rise to the fluid, for instance a local
      infection or metastasis, or whether the cavity is connected to organs or fluid
      compartments nearby etcetera. The results of the laboratory investigations often
      have () direct consequences. As the investigation of uncommon body fluids is
      distinct from routine laboratory analyses it requires special attention. This
      paper presents an overview of the characteristics of uncommon human body fluids,
      constituents useful as markers for recognizing and differentiating fluids and
      considerations that have to be taken into account when interpreting the results
      of analyses. In addition a number of practical recommendations for approaching
      the task of identifying uncommon body fluids are given.

PMID- 28495389
TI  - Clinical trainees' responses to parents who question evidence-based
      recommendations.
AB  - OBJECTIVE: We examined clinicians' attitudes, beliefs, and behavioral intentions
      about discussing evidence and eliciting values when patients question
      recommendations. METHODS: We randomized trainees to read one of three scenarios
      about a parent of a one-year-old: 1) overuse (parent requests antibiotics for
      presumed viral infection); 2) equipoise (tubes for recurrent ear infections); 3)
      underuse (parent hesitates about vaccination). Participants then answered survey
      questions. Outcomes included time spent clarifying values (primary), attitudes
      and beliefs about the parent (secondary). RESULTS: 132 medical students and
      pediatric residents enrolled; 119 (90%) completed the study. There were no
      differences in time participants would spend clarifying values (antibiotics 26+/
      12%; equipoise 28+/-11%; vaccine-hesitancy 22+/-11%; p=0.058). Participants in
      the vaccine-hesitancy group (vs. other groups) would spend less time answering
      questions (p=0.006). Participants in the antibiotics (vs. equipoise) group
      perceived the parent as difficult (p=0.0002). Those in the vaccine-hesitancy
      group (vs. other groups) perceived the parent as difficult, saw less value in the
      conversation, and had lower respect for the parent's views (all ps<0.0001). Most
      (76%) wanted additional training navigating these discussions. CONCLUSION:
      Clinicians' attitudes may impact conversations when patients question evidence
      based recommendations. PRACTICE IMPLICATIONS: Clinicians should consider ways to
      discuss evidence and clarify patients' values to optimize health without damaging
      patient-clinician relationships.

PMID- 28495390
TI  - Interaction-A missing piece of the jigsaw in interpreter-mediated medical
      consultation models.
AB  - In 2015, at the International Conference on Communication in Healthcare in New
      Orleans, USA, we formed a symposium panel to discuss and debate how
      interdisciplinary research can inform interpreter-mediated medical consultation
      training. In all our work, a recurring theme is not just the strengths but also
      the shortcomings of the guidelines proposed in the textbooks and widely used in
      medical education. This paper is an account of our multidisciplinary reflections
      on a prominent issue of the lack of attention to interaction in communications,
      which shed light on the limitations of these guidelines and clinical
      communication models. We propose that an international network be established for
      all stakeholders to foster interprofessional and interdisciplinary collaboration
      for research and clinical interventions, and to inform training and policy
      making.

PMID- 28495392
TI  - Elderly polypharmacy patients' needs and concerns regarding medication assessed
      using the structured patient-pharmacist consultation model.
AB  - OBJECTIVE: To evaluate elderly polypharmacy patients' needs and concerns
      regarding medication through the Structured Patient-Pharmacist Consultation
      (SPPC). METHODS: Older patients on chronic treatment with >=5 medications were
      asked to fill in the SPPC form at home. A consultation with the community
      pharmacist, structured according to patient's answers, followed within 2-4 weeks.
      Logistic regression associated patients' individual treatment with care issues
      and consultation outcomes. RESULTS: Out of 440 patients, 39.5% experienced
      problems, and 46.1% had concerns about medication use. 122 patients reported
      reasons for discontinuing treatment. The main outcome of the consultation was a
      better understanding of medication use (75.5%). Side effects and/or non-adherence
      were identified in 50% of patients, and 26.6% were referred to the doctor. Atrial
      fibrillation, COPD, anticoagulants, benzodiazepines, and beta
      agonists/corticosteroids were associated with problems during medication use.
      Patients with diabetes improved their understanding of medication use
      significantly. CONCLUSION: Patients on benzodiazepines, anticoagulants, and beta
      agonists/corticosteroids, with atrial fibrillation and/or COPD, may have a higher
      potential for non-adherence. Counseling patients based on the SPPC model may be
      particularly useful for patients with diabetes. PRACTICE IMPLICATIONS: The SPPC
      model is a useful tool for counseling based on patient needs.

PMID- 28495391
TI  - Engaging women with an embodied conversational agent to deliver mindfulness and
      lifestyle recommendations: A feasibility randomized control trial.
AB  - OBJECTIVE: This randomized controlled trial evaluates the feasibility of using an
      Embodied Conversational Agent (ECA) to teach lifestyle modifications to urban
      women. METHODS: Women were randomized to either 1) an ECA (content included:
      mindfulness, stress management, physical activity, and healthy eating) or 2)
      patient education sheets mirroring same content plus a meditation CD/MP3 once a
      day for one month. General outcome measures included: number of stress management
      techniques used, physical activity levels, and eating patterns. RESULTS: Sixty
      one women ages 18 to 50 were enrolled. On average, 51% identified as white, 26%
      as black, 23% as other races; and 20% as Hispanic. The major stress management
      techniques reported at baseline were: exercise (69%), listening to music (70%),
      and social support (66%). After one month, women randomized to the ECA
      significantly decreased alcohol consumption to reduce stress (p=0.03) and
      increased daily fruit consumption by an average of 2 servings compared to the
      control (p=0.04). CONCLUSION: It is feasible to use an ECA to promote health
      behaviors on stress management and healthy eating among diverse urban women.
      PRACTICE IMPLICATIONS: Compared to patient information sheets, ECAs provide
      promise as a way to teach healthy lifestyle behaviors to diverse urban women.

PMID- 28495393
TI  - Correction of chin ptosis.
AB  - Chin ptosis is described as a descent of the soft tissue from the symphyseal
      region to a position under the lower contour of the mandible. Given its
      multifactorial causes, treatment must be determined on a patient-by-patient
      basis. While augmentation of the submental crease is a versatile option for the
      correction of chin ptosis, this only corrects the soft tissue component. A
      technical modification to treat dynamic chin ptosis, associated with bone
      reduction in the mandibular symphysis, is presented here.

PMID- 28495394
TI  - Chronic temporomandibular joint pain: two cases of osteoid osteoma and a review
      of the literature.
AB  - Osteoid osteoma is a benign bone tumour with self-limiting growth potential
      occurring in any part of the body. Two rare cases of a pathologically proven
      osteoid osteoma invading the temporomandibular joint (TMJ) are reported herein.
      This article also reviews the cases of osteoid osteoma of the craniofacial
      complex reported in the English-language literature to date. Although the
      clinical presentation of osteoid osteoma in the jaw differs from that of osteoid
      osteoma in the more common locations, the radiographic features are similar. In
      both cases presented, computed tomography revealed a small round osseous lesion
      with sharp margins in the TMJ. Bone scintigraphy was performed in order to
      differentiate the lesions from other osseous lesions. Both patients underwent
      surgical excision of the lesion with immediate relief of the pain. The importance
      of early recognition of the clinical and imaging characteristics of an osteoid
      osteoma of the TMJ is emphasized, in order to prevent misdiagnosis and avoid
      discouraging therapies.

PMID- 28495395
TI  - Study of the variables associated with local complement activation in IgA
      nephropathy.
AB  - OBJECTIVES: 1. To identify the variables that are associated with urinary levels
      of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2.
      To analyse whether urinary levels of MBL and/or C4d are useful for identifying
      the presence of mesangial deposits of C4d/MBL. PATIENTS AND METHOD: A total of 96
      patients with IgA nephropathy were studied. Demographic, clinical and biochemical
      variables were recorded at the time of diagnosis. Renal lesions were quantified
      using the Oxford classification. Immunohistochemical staining for MBL, MASP-2,
      properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the
      levels of properdin, MBL, C4d and C5b-9 were determined. RESULTS: In multivariate
      analysis, the independent predictors of C4d and MBL levels in urine were the
      mesangial deposits of each protein and, to a lesser extent, the urinary protein
      excretion. The independent predictors of urinary levels of C5b-9 were MBL
      properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95%
      CI: 58,7 to 99) and a specificity of 73% (95% CI: 54-87) for detecting mesangial
      C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62-95) and
      a specificity of 81.6% (95% CI: 65-92) for identifying mesangial deposits of MBL.
      CONCLUSION: The main predictor of urinary concentration of C4d and MBL was the
      presence of their respective mesangial deposits. Urine MBL may contribute to
      complement activation in the tubular luz through the lectin pathway. Urinary
      levels of MBL and C4d could be sensitive and specific biomarkers for the
      identification of patients with mesangial deposits of MBL and C4d.

PMID- 28495396
TI  - Cardiovascular risk prediction in chronic kidney disease patients.
AB  - INTRODUCTION: Scores underestimate the prediction of cardiovascular risk (CVR) as
      they are not validated in patients with chronic kidney disease (CKD). Two of the
      most commonly used scores are the Framingham Risk Score (FRS-CVD) and the ASCVD
      (AHA/ACC 2013). The aim of this study is to evaluate the predictive ability of
      experiencing a cardiovascular event (CVE) via these 2scores in the CKD
      population. MATERIAL AND METHODS: Prospective, observational study of 400
      prevalent patients with CKD (stages 4 and 5 according the KDOQI; not on
      dialysis). Cardiovascular risk was calculated according to the 2scores and the
      predictive capacity of cardiovascular events (atherosclerotic events: myocardial
      infarction, ischaemic and haemorrhagic stroke, peripheral vascular disease; and
      non-atherosclerotic events: heart failure) was analysed. RESULTS: Forty-nine
      atherosclerotic cardiovascular events occurred in 40.3+/-6.6 months of follow-up.
      Most of the patients were classified as high CVR by both scores (59% by the FRS
      CVD and 75% by the ASCVD). All cardiovascular events occurred in the high CVR
      patients and both scores (FRS-CVD log-rank 12.2, P<.001, HR 3.1 [95% CI: 1.3-7.1]
      P: 0.006 and ASCVD log-rank 8.5 P<.001, HR 3.2 [95% CI: 1.1-9.4] P: 0.03) were
      independent predictors adjusted to renal function, albuminuria and previous
      cardiovascular events. CONCLUSION: The cardiovascular risk scores (FRS-CVD and
      ASCVD [AHA/ACC 2013]) can estimate the probability of atherosclerotic
      cardiovascular events in patients with CKD regardless of renal function,
      albuminuria and previous cardiovascular events.

PMID- 28495397
TI  - Safety profile and long-term engraftment of human CD31+ blood progenitors in bone
      tissue engineering.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) participate in angiogenesis and
      induce favorable micro-environments for tissue regeneration. The efficacy of EPCs
      in regenerative medicine is extensively studied; however, their safety profile
      remains unknown. Therefore, our aims were to evaluate the safety profile of human
      peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of
      hEPCs in bone tissue engineering. METHODS: hEPCs were isolated from peripheral
      blood, cultured and characterized. beta tricalcium phosphate scaffold (betaTCP,
      control) or 106 hEPCs loaded onto betaTCP were transplanted in a nude rat
      calvaria model. New bone formation and blood vessel density were analyzed using
      histomorphometry and micro-computed tomography (CT). Safety of hEPCs using
      karyotype analysis, tumorigenecity and biodistribution to target organs was
      evaluated. RESULTS: On the cellular level, hEPCs retained their karyotype during
      cell expansion (seven passages). Five months following local hEPC
      transplantation, on the tissue and organ level, no inflammatory reaction or
      dysplastic change was evident at the transplanted site or in distant organs.
      Direct engraftment was evident as CD31 human antigens were detected lining vessel
      walls in the transplanted site. In distant organs human antigens were absent,
      negating biodistribution. Bone area fraction and bone height were doubled by hEPC
      transplantation without affecting mineral density and bone architecture.
      Additionally, local transplantation of hEPCs increased blood vessel density by
      nine-fold. CONCLUSIONS: Local transplantation of hEPCs showed a positive safety
      profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral
      density change was found. These results bring us one step closer to first-in
      human trials using hEPCs for bone regeneration.

PMID- 28495398
TI  - True and false contraindications to vaccines.
AB  - Nowadays, the awareness of risks related to infectious diseases has decreased,
      whereas THE perception of risks related to vaccination is growing. Therefore, it
      may be difficult for health care providers to convince people of the importance
      of vaccination and adherence to the immunisation schedule. Selected situations
      that might raise uncertainties about vaccine recommendations are discussed in
      order to help health care providers to identify real and perceived
      contraindications to vaccines, and cases to be referred to specialised pre
      vaccination consultation due to an increased risk of adverse events to vaccines.

PMID- 28495400
TI  - Rapid breakthrough of 131I in an in vitro human epidermis model.
AB  - Skin contamination with radionuclides may cause local radiation damage, but also
      systemic distribution if the nuclides penetrate the epidermal membrane. Detailed
      information of the skin absorption of radionuclides is of importance for e.g.
      dose estimations and development of decontamination strategies. In the present
      study, penetration of 131I through human epidermis was studied using an in vitro
      flow through diffusion chamber. Epidermis was exposed to a Na131I-solution, used
      in nuclear medicine, and the potential concentration-dependency of skin
      penetration was examined by including two concentrations of non-radioactive NaI.
      Penetration of 131I occurred after a few minutes of exposure and steady state
      penetration rate was obtained after about 50-70min independently of the iodine
      concentration and receptor solution used. The two receptor solutions evaluated;
      phosphate buffered saline solution and an ethanol and water-mixture (1:1),
      resulted in significantly higher penetration rate of 131I using the ethanol and
      water-mixture. The penetration of iodine was calculated to be concentration
      dependent independently of the receptor solution utilized. In addition,
      radioactive iodine did not accumulate in epidermis in the in vitro-model used. In
      conclusion, the present study provides detailed information on the rapid iodine
      penetration at the early phase of radionuclide exposure, defined as the first
      30min of the experiment, and is clearly suitable for decontamination studies. In
      addition, methodological aspects, e.g. impact of the receptor solution, should
      carefully be considered in studies of radionuclide skin penetration using in
      vitro-techniques.

PMID- 28495399
TI  - Evaluation of Toll-like-receptor gene family variants as prognostic biomarkers in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is
      persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in
      the activation of innate and adaptive immune responses, and influence the
      activity of NFkappaB, a key player in chronic inflammation. We aimed at
      investigating the association of TLR allelic variants with susceptibility and
      severity of RA through a systematic, high-throughput, analysis of TLR genes. All
      coding exons and flanking regions of nine members of the TLR family (TLR1-9) were
      analyzed in 66 patients with RA and 30 healthy controls by next generation
      sequencing. We focussed on three single allelic variants, N248S in TLR1, Q11L in
      TLR7 and M1V in TLR8 based on the allelic frequencies in both patient and control
      populations, the predicted impact on protein function and the novelty in RA
      research. Analysis of these selected variants in a larger cohort of 402 patients
      with RA and in 208 controls revealed no association with susceptibility. However,
      the M1V allele was associated with a lower need for disease-modifying
      antirheumatic drugs (DMARDs) (p=0.008) and biologic treatments (p=0.021).
      Functional studies showed that the M1V variant leads to a reduced production of
      inflammatory cytokines, IL-1beta, IL-6 and TNFalpha, in response to TLR8
      agonists. Thus, the presence of this variant confers a significant protective
      effect on disease severity. These results show for the first time the association
      between the M1V variant of TLR8 and reduced disease severity in RA, which could
      have prognostic value for these patients.

PMID- 28495402
TI  - Associations of tumor necrosis factor-alpha-308 polymorphism with dengue
      infection: A systematic review and meta-analysis.
AB  - Inconsistency of reported associations between the tumor necrosis factor-alpha
      308 (TNFalpha-308) polymorphism (rs1800629) and dengue virus infection prompted a
      meta-analysis, to obtain more precise estimates. A literature search yielded 14
      case-control studies. We calculated pooled odds ratios (OR) and 95% confidence
      intervals in three groups according to severity, dengue fever (DF), dengue
      hemorrhagic fever (DHF) and dengue (DEN) using standard genetic models. Pooled
      ORs were subjected to modifier treatment where re-analysis was confined to Hardy
      Weinberg compliant (HWC) studies. Heterogeneity of outcomes warranted examining
      their sources with outlier treatment. In subgroup analysis, we compared Asian and
      South/Central American (SCA)/Brazilian effects. Overall pooled outcomes yielded
      no significant effects (OR 0.66-1.44, P=0.08-0.96). In the dominant-codominant
      model, pooled effects were heterogeneous (I2=47%-71%) which was lost/reduced
      (I2=0%-43%) when outlier treatment was applied. This also yielded significant
      associations (OR 0.68-0.77, P=0.02-0.05). Our results are best seen in the Asian
      subgroup, which in itself already yielded significant effects in DEN (OR 0.62
      0.67, P=0.01-0.02). These reduced risk findings were significant from the tests
      of interaction (P=0.001-0.02) which highlights the protective effects of TNFalpha
      308 among Asians. TNFalpha-308 effects on dengue are based on significance and
      non-heterogeneity of the post-outlier outcomes in the dominant and codominant
      models. Here, pooled effects may also be ethnic specific, where Asians are
      protected but not SCA. Both modified and Asian effects are up to 38% protective.

PMID- 28495401
TI  - Transcriptomic analysis of porcine PBMCs in response to FMDV infection.
AB  - Foot-and-mouth disease (FMD) is a significant zoonotic infectious disease. It has
      an important economic impact throughout the world. As well, it is a considerable
      threat to food security. At present, the molecular mechanism of FMDV infection is
      not clear to a large extent. Innate immune response is the first line of defense
      against infectious diseases. The systematic analysis of the host immune response
      to infection has an important role in understanding the pathogenesis of
      infection. However, there are few reports about effect of immune regulation on
      virus replication in the interaction of virus and host cellular. High-throughput
      RNA-seq technology as a powerful and efficient means for transcript analysis
      provides a new insight into FMDV study. In this study, RNA extracted from pig
      PBMCs infected with O subtype FMDV at 4 dpi. A total of 29942658 and 31452917
      Illumina read pairs were obtained from the non-infected (NI) group and infected
      (I) group, respectively. The clean bases for all samples are 3.61G (NI group) and
      3.79G (I group), respectively. The clean reads of the NI and I group that mapped
      to pig genome data were 47195073 (81.82%) and 46556714 (76.85%), respectively.
      Most of the clean reads were distributed in the exon region, followed by intron
      region and intergenic region. Differently expressed (DE) genes were analyzed
      using edgeR software. 451 genes were differentially expressed between the
      infected and the non-infected groups. According to the comparison analysis, more
      genes were down-regulated in the non-infected samples than in those infected with
      FMDV.66 out of 451 genes were down-regulated, 385 out of 451 genes were up
      regulated following FMDV infection. For function classification and pathway
      analysis, among 17741 assembled unigenes, there are 349 genes which are different
      genes of GO notes. Moreover, 49 genes were down-regulated, 300 genes were up
      regulated associate with GO term. 1621 were successfully annotated by GO
      assignments, belonging to one or more of the three categories: biological
      process, cellular component, and molecular function. According to KEGG
      analysis,the main pathway was represented including protein processing in
      endoplasmic reticulum, phagosome, cell cycle and cytokine-cytokine receptor
      interaction. Some key DE genes related to immune process and signaling pathways
      were analyzed and quantified by RT-PCR. This is the first systematical
      transcriptome analysis of pig PBMCs infected by FMDV. These findings will help us
      better understand the host Cell-FMDV interaction and its relationship to
      pathogenesis, as well as contribute to the prevention and control of FMDV.

PMID- 28495403
TI  - Effect of insecticide-treated bed nets on house-entry by malaria mosquitoes: The
      flight response recorded in a semi-field study in Kenya.
AB  - Insecticide-treated nets are currently a major tool to reduce malaria
      transmission. Their level of repellency affects contact of the mosquito with the
      net, but may also influence the mosquito's entry into the house. The response of
      host-seeking malaria mosquitoes approaching the eave of an experimental house was
      recorded within a large screen house. We compared entry- and exit rates in
      relation to the presence in the house of different insecticide-treated bed nets
      (ITNs) with an untreated net. Mosquitoes were lured towards the house by
      dispensing a synthetic host-odour blend from within the net in the house.
      Complementary WHO bioassays revealed that the treated nets caused high knock-down
      and mortality responses to the Anopheles gambiae sensu stricto strain tested.
      The proportion of mosquitoes that came into view of the cameras and subsequently
      entered the house did not differ between treated nets and the untreated net.
      Treated nets did not affect proportions of mosquitoes that exited the house and
      departed from view around the eave. However, the percentage of house-leaving and
      re-entering mosquitoes when an insecticide- treated net was present, was lower
      than in the presence of an untreated net. Our results indicated that there was no
      spatial repellent effect from pyrethroid-treated nets that influences house-entry
      at eave level. It is argued that the toxic effect of treated bed nets resulted in
      a reduced number of mosquitoes re-entering the house, which could thereby affect
      malaria transmission in neighbouring, unprotected houses.

PMID- 28495404
TI  - Does Aedes albopictus (Diptera: Culicidae) play any role in Usutu virus
      transmission in Northern Italy? Experimental oral infection and field evidences.
AB  - This study evaluated the vector competence of Aedes albopictus in transmitting
      USUV after oral infection under laboratory conditions. Ae. albopictus showed a
      low vector competence for USUV, although the positive body sample found with a
      very high number of viral copies at one week post infection indicates that a
      replication in the mosquito body can occur, and that USUV can escape the midgut
      barrier. Field data from an extensive entomological arboviruses surveillance
      program showed a relevant incidence of Ae. albopictus USUV positive pools in the
      period 2009-2012 while all pools were negative from 2013 on. No conceivable
      explanation regarding this field evidence was addressed, suggesting that
      attention must be paid to the trend of development of this vector-pathogen
      association, being aware of the potential rapid arbovirus' adaptation to new
      vectors, to prevent possible new disease's emergence.

PMID- 28495405
TI  - Trypanosoma cruzi I: Towards the need of genetic subdivision?, Part II.
AB  - Chagas disease is a complex zoonosis caused by the kinetoplastid parasite
      Trypanosoma cruzi. This protozoan exhibits remarkable genetic diversity evinced
      in at least six Discrete Typing Units (DTUs) with the foreseen emergence of a
      genotype associated to bats (TcBat). T. cruzi I is the DTU with the broadest
      geographical distribution and associated to severe cardiomyopathies. In 2011, we
      published a review questioning the need for genetic subdivision within TcI.
      However, after six years of intensive research. Herein, we attempted to determine
      if TcI should be subdivided or not in the light of the current genetic,
      biological, clinical and ecological data. The future perspectives are discussed.

PMID- 28495407
TI  - In Reply: The Only Thing We Have to Blame Is Blame Itself.

PMID- 28495408
TI  - Is the Level of Nitric Oxide in the Dental Follicular Tissues of Impacted Third
      Molars With a History of Recurrent Pericoronitis a True Marker of Oxidative
      Stress?
AB  - PURPOSE: Nitric oxide (NO) is an indicator of oxidative stress in several
      tissues. Its role in dental follicular (DF) tissues of impacted third molars with
      a history of recurrent pericoronitis is not well elucidated. The present study
      compared NO levels between inflamed and noninflamed DF tissues of impacted third
      molars with a history of recurrent pericoronitis. MATERIALS AND METHODS: A cross
      sectional study was designed. The study sample included inflamed DF tissues (test
      group) with certain local inflammatory symptoms, such as pain, tenderness,
      swelling, and erythema and noninflamed DF tissues (control group) without local
      inflammatory symptoms of impacted mandibular third molars. Each patient
      contributed only 1 specimen to the samples. All tissues samples were
      biochemically investigated for NO levels as an indicator of oxidative stress. The
      primary predictor variable was inflammatory status; secondary predictor variables
      were age and gender. The primary outcome variable was NO level. Descriptive and
      comparative analyses were conducted. RESULTS: The test group consisted of 57
      patients (28 men, 29 women; mean age, 23.28 +/- 5.16 yr) and the control group
      consisted of 57 patients (30 men, 27 women; mean age, 23.02 +/- 5.42 yr). No
      relevant intergroup differences were noted for demographic findings such as age
      and gender. NO levels were significantly higher in inflamed DF tissues of
      impacted third molars than in noninflamed DF tissues (P < .05). CONCLUSION:
      Results of this study showed that NO might be used as an indicator of oxidative
      stress and the necessity to remove impacted mandibular third molars with a
      history of recurrent pericoronitis.

PMID- 28495406
TI  - Nuclear Receptor Function through Genomics: Lessons from the Glucocorticoid
      Receptor.
AB  - Unlocking the therapeutic potential of the glucocorticoid receptor (GR) has
      motivated a search for small molecules that selectively modulate its ability to
      activate or repress gene transcription. Recently, breakthrough studies in the
      field of genomics have reinvigorated debate over longstanding transcriptional
      models explaining how GR controls tissue-specific gene expression. Here, we
      highlight these genomic studies with the dual goals of advancing understanding of
      nuclear receptor-mediated transcription and stimulating thought on the
      development of anti-inflammatory and immunosuppressive ligands for GR that have
      reduced harmful effects on metabolism.

PMID- 28495409
TI  - Effect of Asymptomatic Visible Third Molars on Periodontal Health of Adjacent
      Second Molars: A Cross-Sectional Study.
AB  - PURPOSE: Evidence that asymptomatic third molars (M3s) negatively affect their
      adjacent second molars (A-M2s) is limited. The present study evaluated the
      association between visible M3s (V-M3s) of various clinical status with the
      periodontal pathologic features of their A-M2s. PATIENTS AND METHODS: Subjects
      with at least 1 quadrant having intact first and second molars, either with V-M3s
      and symptom free or without adjacent V-M3s, were enrolled in the present cross
      sectional investigation. Periodontal parameters, including plaque index (PLI),
      bleeding on probing (BOP), probing pocket depth (PPD), and at least 1 site with a
      PPD of 5 mm or more (PPD5+), obtained from M2s were analyzed according to the
      presence or absence of V-M3s or the status of the M3s. The chi2 test or t test
      was used to compare the mean PLI, PPD, BOP percentage, and PPD5+ percentage. The
      association of PPD5+ with V-M3 status was assessed using a multivariable logistic
      regression model (quadrant-based analysis), and variances were adjusted for
      clustered observations within subjects. RESULTS: In total, 572 subjects were
      enrolled in the study, and 423 had at least 1 V-M3. At the in-quadrant level, the
      presence of a V-M3 significantly increased M2 pathologic parameters, including
      PLI, PPD, BOP, and PPD5+. When analyzed using a multivariate logistic regression
      model, impacted M3s and normally erupted M3s significantly elevated the risk of
      PPD5+ on their A-M2s (odds ratio 3.20 and 1.67, respectively). Other factors
      associated with an increased odds of PPD5+ were mandibular region and older age.
      Finally, the patient-matched comparison showed that the percentage of BOP and
      PPD5+ on M2s increased when V-M3s were present. CONCLUSIONS: Irrespective of
      their status, the presence of V-M3s is a risk factor for the development of
      periodontal pathologic features in their A-M2s. Although the prophylactic removal
      of asymptomatic V-M3s remains controversial, medical decisions should be made as
      early as possible, because, ideally, extraction should be performed before
      symptom onset.

PMID- 28495410
TI  - A Case-and-Control, Multisite, Positive Controlled, Prospective Study of the
      Safety and Effectiveness of Immediate Inferior Alveolar Nerve Processed Nerve
      Allograft Reconstruction With Ablation of the Mandible for Benign Pathology.
AB  - PURPOSE: This study determined whether immediate reconstruction of the inferior
      alveolar nerve with a long (>4.5 cm) processed nerve allograft (PNA) in
      conjunction with simultaneous ablation and reconstruction of the mandible would
      be effective in safely restoring subjective sensation and achieving functional
      sensory recovery. MATERIALS AND METHODS: Patients (5 to 70 yr old) requiring
      resection of the unilateral or bilateral mandible for benign pathology were
      included. The graft had to be longer than 4.5 cm. Results of sensory nerve tests
      and 3 different surveys (Direct Path, Numerical Rating Scale, Word Choice) were
      collected before surgery and at 3, 6, and 12 months after surgery. Safety data
      were recorded. RESULTS: Twenty-six patients participated in this study. Three
      patients served as positive controls (no nerve repair). Five in the repair group
      and 1 in the positive control group were lost to follow-up. Data during a 1-year
      period were collected on 18 patients (7 male and 11 female; mean age, 26.4 yr;
      range, 10 to 64 yr). The mean length of the PNA was 62.7 mm (range, 45 to 70 mm).
      Seventeen of 18 patients had S4 sensory scores preoperatively and the
      postoperative score was S4 at 3 months in 3, at 6 months in 3, and at 1 year in
      12. Scores for positive control patients never exceeded S2. Numerical rating
      scales and word choices were not statistically different from presurgical scores
      at 6 and 12 months. There were no adverse events. CONCLUSIONS: The PNA is safe
      and effective when immediately inserted with resection and reconstruction of the
      mandible: 90% of patients achieved functional sensory recovery and reported
      similar sensations to preoperative subjective values.

PMID- 28495411
TI  - Is Low-Level Laser Therapy Effective for Treatment of Neurosensory Deficits
      Arising From Sagittal Split Ramus Osteotomy?
AB  - PURPOSE: This study investigated the effectiveness of low-level laser therapy
      (LLLT) for treating neurosensory impairment after bilateral sagittal split
      osteotomy (BSSO). MATERIALS AND METHODS: This randomized, double-blinded, split
      mouth trial included patients requiring BSSO. After surgery, 1 side of each
      patient was randomly assigned to laser therapy and the other side served as the
      control. At 24, 48, and 72 hours after surgery, LLLT was accomplished by
      intraoral application of a 660-nm laser around the surgical site (200 mW, 10
      seconds, 2 J, 1.5 J/cm2) followed by extraoral irradiation by an 810-nm laser
      (200 mW, 10 seconds, 2 J, 7 J/cm2) along the distribution of the inferior
      alveolar nerve. Subsequently, extraoral irradiation was repeated 2 times per week
      for 3 weeks along the path of the inferior alveolar nerve, lower lip, and chin.
      On the control side, the treatment was similar to the laser side but with laser
      simulation. The main outcome was assessing nerve damage by a "2-point
      discrimination test" before and up to 60 days after surgery. RESULTS: The sample
      consisted of 16 patients. No significant difference was found between the laser
      and control sides before and after surgery and on postoperative days 15 and 30 (P
      > .05). The 2-point discrimination distance was significantly shorter on the
      laser side than on the control side on postoperative days 45 and 60 (P < .05).
      CONCLUSION: LLLT was effective in the treatment of neurosensory disturbances
      arising from BSSO. Therefore, LLLT can be recommended to accelerate the recovery
      of sensory aberrations in patients undergoing BSSO.

PMID- 28495412
TI  - Radiofrequency Microdebridement Versus Surgical Decompression for Achilles
      Tendinosis: A Randomized Controlled Trial.
AB  - Achilles tendinosis is primarily managed nonoperatively with activity
      modification and physiotherapy, although surgery can be required. This has
      classically involved surgical decompression of the Achilles tendon, although the
      use of radiofrequency microdebridement has been suggested as a novel minimally
      invasive alternative. We present a randomized controlled trial comparing
      radiofrequency microdebridement using the Topaz(r) microdebrider wand and
      traditional surgical decompression. All patients with Achilles tendinosis
      referred to a single surgeon and meeting the inclusion criteria were invited to
      participate in our single-blinded, randomized controlled study. The Victorian
      Institute of Sports Assessment-Achilles (VISA-A) questionnaire and the visual
      analog scale were used as measures at baseline and 6 months postoperatively. From
      2009 to 2014, 16 patients were randomized to traditional decompression treatment
      and 20 to Topaz(r) treatment. All surgical procedures were performed as day-case
      procedures with the patient under general anesthetic by a single surgeon. No
      significant differences were found between the groups in demographic data. At 6
      months after intervention, both groups demonstrated an improvement in the
      Victorian Institute of Sports Assessment-Achilles and visual analog scale scores
      compared with baseline, with no difference found between treatment modalities at
      6 months. The Topaz(r) microdebrider resulted in variable outcomes after surgery
      and is not without complications. Regarding the patient-reported outcome
      measures, Topaz(r) conferred no additional benefit compared with traditional
      surgical decompression and we have stopped using Topaz(r) in our treatment of
      Achilles tendinosis.

PMID- 28495413
TI  - The Central Vacuole of the Diatom Phaeodactylum tricornutum: Identification of
      New Vacuolar Membrane Proteins and of a Functional Di-leucine-based Targeting
      Motif.
AB  - Diatoms are unicellular organisms evolved by secondary endosymbiosis. Although
      studied in many aspects, the functions of vacuolar-like structures of these
      organisms are rarely investigated. One of these structures is a dominant central
      vacuole-like compartment with a marbled phenotype, which is supposed to represent
      a chrysolaminarin-storing and carbohydrate mobilization compartment. However,
      other functions as well as targeting of proteins to this compartment are not
      shown experimentally. In order to study trafficking of membrane proteins to the
      vacuolar membrane, we scanned the genome for intrinsic vacuolar membrane proteins
      and used one representative for targeting studies. Our work led to the
      identification of several proteins located in the vacuolar membrane as well as
      the sub-compartmentalized localization of one protein. In addition, we show that
      a di-leucine-based motif is an important signal for correct targeting to the
      central vacuole of diatoms, like it is in plants.

PMID- 28495414
TI  - The NHS is no place for immigration enforcement.

PMID- 28495415
TI  - Rhinovirus - From bench to bedside.
AB  - Rhinovirus has been neglected in the past because it was generally perceived as a
      respiratory virus only capable of causing mild common cold. Contemporary
      epidemiological studies using molecular assays have shown that rhinovirus is
      frequently detected in adult and pediatric patients with upper or lower
      respiratory tract infections. Severe pulmonary and extrapulmonary complications
      are increasingly recognized. Contrary to popular belief, some rhinoviruses can
      actually replicate well at 37  degrees C and infect the lower airway in humans.
      The increasing availability of multiplex PCR panels allows rapid detection of
      rhinovirus and provides the opportunity for timely treatment and early
      recognition of outbreaks. Recent advances in the understanding of host factors
      for viral attachment and replication, and the host immunological response in both
      asthmatic and non-asthmatic individuals, have provided important insights into
      rhinovirus infection which are crucial in the development of antiviral treatment.
      The identification of novel drugs has been accelerated by repurposing clinically
      approved drugs. As humoral antibodies induced by past exposure and vaccine
      antigen of a particular serotype cannot provide full coverage for all rhinovirus
      serotypes, novel vaccination strategies are required for inducing protective
      response against all rhinoviruses.

PMID- 28495416
TI  - Invasive fungal rhinosinusitis presenting as Bell's palsy in a kidney and liver
      transplant recipient.

PMID- 28495417
TI  - False positive ketamine urine immunoassay screen result induced by quetiapine: A
      case report.
AB  - Ketamine immunoassay urine drug screen (UDS) is commonly used in Taiwan. However,
      there was limited report about possible drug which may cause false positive
      results in ketamine screen test. We report two cases who used quetiapine showed
      positive in ketamine urine immunoassay screen initially, and found to be false
      positive in confirmation test. Clinicians should be aware of the false positive
      result of ketamine UDS caused by currently used medication.

PMID- 28495418
TI  - Structural study of the cremaster muscle in patients with retractile testis.
AB  - OBJECTIVE: To analyze the structure of the cremaster in patients with retractile
      testis (RT), comparing the distribution of nerves, elastic system and muscles
      with patients having cryptorchidism and inguinal hernia (IH). PATIENTS AND
      METHODS: We studied 31 patients, 17 with RT (mean age=5.17years); 9 with IH (mean
      age=2.6) and 5 with cryptorchidism (mean age=3). A cremaster biopsy was performed
      and submitted to routine histological processing and studied using histochemistry
      and immunohistochemistry. The samples were photographed under an Olympus BX51
      microscope. The images were processed with the Image J software and the cremaster
      muscle structures were quantified. Means were compared statistically using ANOVA
      and the unpaired t-test (p<0.05). RESULTS: There were no differences (p=0.08) in
      diameter of muscle fiber between the groups. The muscle fiber density differed
      between patients with RT and IH (p=0.02): RT (mean=17.71%, SD=16.67), IH
      (mean=38.06%, SD=14) and cryptorchidism (mean=21.47%, SD=16.18). There was no
      difference (p=0.07) in the density of elastic fibers in the three groups. We
      observed a lower concentration of cremaster nerves of patients with RT compared
      with IH (p=0.0362): RT (mean=1.72%, SD=0.58), IH (mean=3.28% SD=0.94) and
      cryptorchidism (mean=2.52%, SD=0.53). CONCLUSIONS: Retractile testis is not a
      normal variant, and presented a similar cremaster muscle structure as in patients
      with cryptorchidism. LEVEL OF EVIDENCE: II; prospective comparative study.

PMID- 28495419
TI  - Factors associated with thrombotic complications in pediatric patients with
      vascular malformations: Methodological issue.

PMID- 28495420
TI  - The Vacuum Bell device as a sternal lifter: An immediate effect even with a short
      time use.
AB  - BACKGROUND: To minimize cardiac perforation during the minimally invasive repair
      of pectus excavatum (MIRPE), several surgeons have suggested using a suction
      device to intraoperatively lift the sternum. Whether or not this technique is
      effective for all PE patients is not yet known. As such, our aim was to quantify
      the extent to which a suction device is capable of lifting the sternum with a
      short duration of use. METHODS: 30 PE patients received a low-dose CT scan as
      part of standard PE evaluation. A Vacuum Bell suction was then applied for only
      two minutes, and a repeat CT scan was obtained only at the deepest point of the
      chest wall deformity. We compared chest dimensions before and after Vacuum Bell
      suction. RESULTS: The Vacuum Bell lifted the sternum in all 29 patients included
      in the analysis. The absolute change in depth ranged from 0.29 to 23.67mm
      (M=11.02, SD=6.05). The average improvement in Haller index was 0.76. The suction
      was most effective for individuals with low BMI and smaller chest depths.
      Efficacy was not associated with gender, age, or chest morphology. CONCLUSIONS:
      The Vacuum Bell device effectively lifted the sternum in PE patients with
      different demographics and chest morphologies. Future research is needed to
      address whether or not the device reduces risk of cardiac perforation during
      MIRPE. LEVELS OF EVIDENCE: Prognosis Study Level IV.

PMID- 28495421
TI  - Association of aldose reductase gene polymorphism (C-106T) in susceptibility of
      diabetic peripheral neuropathy among north Indian population.
AB  - AIM/HYPOTHESIS: Polymorphism in aldose reductase (ALR) gene at nucleotide C(
      106)T (rs759853) in the promoter region is associated with susceptibility to
      development of diabetic peripheral neuropathy. The aim of this study was to
      detect the association of the C (-106)T polymorphism of ALR gene and its
      frequency among patients with type 2 diabetes mellitus with and without
      peripheral neuropathy. METHODS: The study subjects were divided into three
      groups. Group I included 356 patients with diabetes having peripheral neuropathy.
      Group II included 294 patients with diabetes without peripheral neuropathy and
      group III included 181 healthy subjects. Genotyping of ALR C(-106)T SNPs was
      performed using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and direct sequencing methods. The genetic risk among the
      groups was compared and tested by calculating odds ratio with 95% class interval.
      RESULTS: ALR 106TT genotype was significantly higher in group I compared to group
      II with an odds ratio of 2.12 (95% CI: 1.22-3.67; p<0.01). Recessive model (CC+CT
      vs. TT), as well as T allele distribution also showed significant association to
      develop neuropathy with relative risk of 1.97 (95% CI: 1.16-3.35; p<0.01) and
      1.36 (95% CI: 1.07-1.72; p=0.01) respectively. CONCLUSION/INTERPRETATION: In
      conclusion, the ALR C-106T polymorphism was associated with higher risk of
      peripheral neuropathy in patients with type 2 diabetes mellitus.

PMID- 28495422
TI  - Reduced frequency of severe hypoglycemia at mild ambient temperatures between 10
      and 20  degrees C: A population-based study under marine west coast climate
      conditions.
AB  - AIMS: To determine the association between ambient temperature and severe
      hypoglycemia. METHODS: This was a prospective observational study performed in a
      prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany)
      and data from the local weather station were evaluated over a 5-year period.
      Lowess-regression analysis was conducted to assess the relationship between
      ambient temperature and frequency of severe hypoglycemia. Additionally, three
      temperature-ranges were defined in order to compare them with each other with
      regard to frequency of severe hypoglycemia (<10 degrees C vs. 10-20 degrees C vs.
      >20 degrees C). RESULTS: In 2592 patients severe hypoglycemia was diagnosed and
      treated by emergency physicians (T1DM: n=829/32%; T2DM: n=1763/68%). The median
      age of patients was 64 (57-72 [20-85]) years. Compared to mild temperatures (10
      20 degrees C) the frequency of severe hypoglycemia increased significantly at
      temperatures above 20 degrees C (+18% (95%-CI: [7%; 22%], p=0.007) and below 10
      degrees C (+15% (95%-CI: [6%; 24%], p<0.001). CONCLUSIONS: The results suggest
      the existence of a "thermal comfort zone" covering a temperature range from 10 to
      20 degrees C in which the frequency of severe hypoglycemia was significantly
      lower than below 10 degrees C and above 20 degrees C.

PMID- 28495423
TI  - The current evidence of statin use affecting glioblastoma prognosis.
AB  - Cholesterol-lowering statins have been postulated to improve cancer outcomes by
      many unconfirmed mechanisms. The prognosis of glioblastoma (GBM) remains dismal,
      and there is a paucity of evidence regarding the potential for preoperative
      statins to exert a benefit upon prognosis. In light of a recent report, the
      current evidence in the literature regarding statin use affecting GBM prognosis
      is discussed.

PMID- 28495424
TI  - Clinical and radiographic outcomes following hinge fracture during open-door
      cervical laminoplasty.
AB  - To investigate the clinical and radiographic fate of fractured hinges in open
      door cervical laminoplasty, 135 segments of 36 patients who had undergone follow
      up for more than two years after open-door cervical laminoplasty due to
      compressive cervical myelopathy were reviewed clinically and radiographically.
      Hinge fractures were identified by the intraoperative finding of obvious
      instability or click sounds (an obvious fracture), or by immediate postoperative
      computed tomography (CT) images showing a discontinuity of both the inner and
      outer cortex or a displacement of more than 1mm at the lamina hinge site (an
      occult fracture). At two years post-surgery, union and displacement of the
      fractured hinges were evaluated with CT and the clinical outcome was assessed by
      the Japanese Orthopedic Association (JOA) and Neck Disability Index (NDI) scores.
      Immediate postoperative CT scans revealed 28 hinge fractures in 16 patients. Only
      three fractures were identified during surgery, with most being identified on
      postoperative CT. Nineteen laminae showed non-displaced cortical discontinuity,
      five were anteriorly displaced by more than 1mm, and four were displaced
      posteriorly. Twenty-five laminae (89.3%) had achieved union according to the two
      year postoperative CT scan. No de novo neurologic symptoms were found to be
      associated with hinge fracture. The two-year postoperative JOA and NDI scores did
      not differ significantly between patients with or without a hinge fracture. Most
      fractures at the hinge site occurred without intraoperative recognition, and
      usually re-unified without significant displacement or adverse clinical effects.
      When hinge fractures occur, careful observation without additional intervention
      is recommended.

PMID- 28495425
TI  - Volume-staged stereotactic radiosurgery for large intracranial arteriovenous
      malformations.
AB  - Stereotactic radiosurgery (SRS) is an effective treatment option for intracranial
      arteriovenous malformations (AVM). However, the treatment of large AVMs (nidus
      volume >=12cm3) with single-session SRS alone yields generally poor outcomes.
      Volume-staged SRS (VS-SRS) is a therapeutic strategy for large AVMs which seeks
      to avoid the disadvantages of single-session SRS, but reports regarding its
      efficacy remain limited. The aim of this retrospective cohort study is to assess
      the outcomes of VS-SRS for large AVMs. We identified all AVM patients who
      underwent VS-SRS at our institution from 2000 to 2015 with >=12months follow-up.
      Baseline and outcomes data were analyzed. A total of 12 patients were selected
      for the study cohort, with a median age of 30years. The median maximum AVM
      diameter and nidus volume were 4.3cm and 13.6cm3, respectively. The Spetzler
      Martin grade was III and IV each in six AVMs (50%). All patients underwent VS-SRS
      in two stages, and the median margin dose was 17Gy for both VS-SRS procedures.
      The median time interval between the two procedures was three months. After a
      median radiologic follow-up duration of 39months, the median degree of AVM volume
      reduction (evaluable in nine patients) was 87% (range 12-99%). The rates of
      radiologically evident, symptomatic, and permanent radiation-induced changes were
      58%, 25%, and 8%, respectively. There were no cases of post-SRS hemorrhage. VS
      SRS substantially reduces the size of large AVMs. A potential role for VS-SRS may
      be to facilitate subsequent definitive intervention to obliterate a shrunken,
      residual nidus.

PMID- 28495426
TI  - Pressure volume curves in cirrhosis: More than meets the eye.

PMID- 28495427
TI  - O-GlcNAcylation: Undesired tripmate but an opportunity for treatment in NAFLD
      HCC.

PMID- 28495428
TI  - Cytotoxic bilirubin metabolites overlooked so far.

PMID- 28495429
TI  - Superoxide-hydrogen peroxide genetic imbalance modulates differentially the
      oxidative metabolism on human peripheral blood mononuclear cells exposed to
      seleno-L-methionine.
AB  - Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene
      polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD)
      is associated with several diseases. Into mitochondria, MnSOD catalyses
      superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high
      MnSOD efficiency and generates the highest HP concentrations that has been
      associated with the risk of several cancer types. Cellular selenoenzymes
      glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are
      essential to HP removal produced in excess in cells. Since, synthesis and
      activities of selenoenzymes are selenium dependent, we hypothesized that AA-MnSOD
      cells could have an improvement on antioxidant status undergoing Seleno-L
      methionine (SeMet) treatment. This study performed an in vitro protocol to
      evaluate the response of peripheral blood mononuclear cells (PBMC) carriers of
      different Val16Ala-MnSOD genotypes exposed to SeMet. SeMet effects on cell
      viability, apoptosis induction and modulation of oxidative variables were
      determined using spectrophotometric, flow cytometry, fluorimetric and
      immunoassays. Gene modulation of antioxidant enzymes was also performed by qRT
      PCR. From an initial protocol using heterozygous (AV) cells was determined that
      1nM SeMet presented a cytoprotective effect. However, whereas this concentration
      did not change AA viability, in VV cells it was cytotoxic by increasing necrosis
      events. SeMet induced higher selenoenzymes levels in AA and VV cells and
      decreased oxidative markers levels including DNA damage. The results suggest a
      pharmacogenetic positive response of SeMet effect on AA-cells. Future studies in
      vivo could be essential to evaluate the potential clinical impact of S-HP
      imbalance after use of foods or supplements containing SeMet.

PMID- 28495430
TI  - Patient Versus Physician Variation in Use of Transradial Percutaneous Coronary
      Intervention.
AB  - The prevalence of radial access for transradial catheterization remains low in
      the United States, occurring in only 28% of cases in the National Cardiovascular
      Data Registry (NCDR) CathPCI. It is unknown whether the low adoption rate has
      been influenced by patient characteristics or is more operator dependent. In a 10
      center study, we compared clinical and demographic characteristics among 323
      radial and 1,506 femoral access percutaneous coronary intervention (PCIs)
      performed by 65 interventionists capable of radial PCI. We created a hierarchical
      logistic regression model to identify operator and patient characteristics
      associated with radial PCI and the median rate ratio to quantify the variation
      across operators. A subset was interviewed to assess health literacy and
      preferences in shared medical decision making. Radial access was used in 17.7% of
      patients. Patient factors associated with lower rate of radial PCI were previous
      PCI (33.4% vs 41.4%, p = 0.008), history of coronary artery bypass graft (8.4% vs
      23.0%, p <0.001), and chronic total occlusion PCI (10.2% vs 17.9%, p <0.001).
      Operator characteristics associated with lower rate of radial PCI are being
      older, being longer in practice, lower number of publications, and Southern
      practice location. The range of radial use across operators was 1% to 99% and the
      median rate ratio was 1.97. Patients with radial access had lower health
      literacy, as assessed by the Rapid Estimate of Adult Literacy in Medicine Revised
      (REALM) score (6.6 +/- 2.6 vs 7.1 +/- 2.0, p = 0.03) but did not differ in their
      preferences for shared decision making. In conclusion, our study demonstrates a
      high degree of variability of radial access for PCI among different operators,
      with few differences in patient characteristics, suggesting that improvement
      efforts should focus on operators.

PMID- 28495432
TI  - Changes in Coagulation and Platelet Activation Markers Following Transcatheter
      Left Atrial Appendage Closure.
AB  - The recommendations for antithrombotic treatment after left atrial appendage
      closure (LAAC) remain empirical, and no data exist on the changes in hemostatic
      markers associated with LACC. The objective of the present study is to determine
      the presence, degree, and timing of changes in the markers of platelet and
      coagulation activation after LAAC. Forty-three patients (mean age 76 +/- 9 years,
      23 men) with atrial fibrillation who underwent successful LACC with the Watchman
      (n = 27) or Amplatzer Cardiac Plug (n = 16) devices were included in the study.
      Patients received antiplatelet therapy after LAAC (aspirin + clopidogrel: 27
      patients; single antiplatelet therapy with aspirin or clopidogrel: 16 patients).
      Prothrombin fragment 1+2 and thrombin-antithrombin III were used as markers of
      coagulation activation, and soluble P-selectin and soluble CD40 ligand were used
      as markers of platelet activation. Measurements of all hemostatic markers were
      performed at baseline just before the procedure, followed by days 7, 30, and 180
      after LAAC. Prothrombin fragment 1+2 and thrombin-antithrombin levels increased
      from 0.27 nmol/L and 4.68 ng/ml, respectively, at baseline to peak values of 0.43
      nmol/L and 9.76 ng/ml, respectively, at 7 days, partially returning to baseline
      levels at days 30 and 180 after LAAC (p <0.001 for both markers). No clinical or
      procedural factors were associated with a greater increase in the markers of
      coagulation activation after LAAC. Levels of soluble P-selectin and soluble CD40
      ligand did not change at any time after LAAC. In conclusion, transcatheter LAAC
      is associated with significant activation of the coagulation system, yet without
      evidence of significant platelet activation.

PMID- 28495433
TI  - Ventricular and Supraventricular Ectopy in Subjects With Early Repolarization.
AB  - Early repolarization (ER) is a common electrocardiographic (ECG) finding that is
      associated with an increased risk of idiopathic ventricular fibrillation and
      sudden cardiac death. This study investigated whether the presence of ER is a
      predictor of ventricular and supraventricular ectopy as a marker for electrical
      instability. Standard 12-lead electrocardiograms of the first follow-up in the
      population-based Study of Health in Pomerania (SHIP-1) (n = 3,300, age 20 to 79
      years) were analyzed to identify subjects with an ER pattern. Ventricular and
      supraventricular ectopy was assessed via portable tele-ECG cards recording 2
      electrocardiograms daily over the course of 4 weeks. Data of 1,630 subjects (n =
      83,833 ECG card recordings, average 51.4 per subject) were analyzed for
      ventricular and supraventricular ectopy using a standardized automated algorithm.
      Associations of ER and several forms of arrhythmias were assessed using a 2-sided
      Fisher's exact test or t test, where appropriate. Overall, prevalence of ER in
      the SHIP-1 population was 4.8%. Presence of ER was not associated with the
      occurrence of ventricular and supraventricular arrhythmias (p >=0.05 for all
      analyses). Furthermore, subgroup analyzes for ER localization (inferior) and ST
      segment morphology (horizontal/descending) did not show any association with
      arrhythmic events. In conclusion, presence of the ER pattern is not associated
      with an increased occurrence of ventricular or supraventricular arrhythmias as
      assessed by serial ECG card recordings in this large population-based sample.

PMID- 28495431
TI  - Evolution of Australian Percutaneous Coronary Intervention (from the Melbourne
      Interventional Group [MIG] Registry).
AB  - Percutaneous coronary intervention (PCI) continues to evolve with shifting
      patient demographics, treatments, and outcomes. We sought to document the
      specific changes observed over a 9-year period in a contemporary Australian PCI
      cohort. The Melbourne Interventional Group is an established multicenter PCI
      registry in Melbourne, Australia. Data were collected prospectively with 30-day
      and 12-month follow-ups. Demographic, procedural, and outcome data for all
      consecutive patients were analyzed with a year-to-year comparison from 2005 to
      2013. National Death Index linkage was performed for long-term mortality
      analysis; 19,858 procedures were captured over 9 years. Patient complexity and
      acuity increased with a higher proportion of traditional risk factors and more
      elderly patients who underwent PCI. Angiographic lesion complexity increased with
      more multivessel coronary artery disease and more American College of
      Cardiology/American Heart Association type B2/C lesions proceeding to PCI. The 30
      day rate of death, myocardial infarction, or target vessel revascularization has
      not changed nor has 12-month mortality, myocardial infarction, or major adverse
      cardiovascular event rates. The strongest independent predictor of long-term
      mortality was cardiogenic shock at presentation (hazard ratio [HR] 2.95, p
      <0.01). Drug-eluting stent use (HR 0.83, p <0.01) and a history of dyslipidemia
      (HR 0.81, p <0.01) were associated with long-term survival. In conclusion, from
      2005 to 2013, we observed a cohort of higher risk clinical and angiographic
      characteristics, with stable long-term mortality.

PMID- 28495434
TI  - Patterns of recurrence and long-term outcomes in patients who underwent
      pancreatectomy for intraductal papillary mucinous neoplasms with high grade
      dysplasia: implications for surveillance and future management guidelines.
AB  - BACKGROUND: While intraductal papillary mucinous neoplasms (IPMNs) with high
      grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions,
      its natural history following resection is unknown. METHODS: A retrospective
      review of HGD-IPMN patients (1999-2015) was performed. Recurrence patterns and
      clinical outcomes following pancreatectomy were analyzed and the indications for
      surgery were explored based on current guidelines. RESULTS: HGD was diagnosed in
      100 of 314 patients (32%) following pancreatectomy for IPMN. IPMNs were
      classified as main duct, branch duct, or mixed in 15, 58 and 27 patients,
      respectively. Following resection, 25 patients had low-risk residual disease in
      the remnant pancreas. With a median follow-up of 35 months (range 1-129), 9
      patients developed progressive or recurrent disease, 4 of whom underwent
      additional pancreatectomy. Three patients developed invasive adenocarcinoma.
      Median time to recurrence was 15 months (range 7-72). Based on the management
      algorithm from the international consensus guidelines, resection was indicated in
      76 patients (76%). Other indications for surgery included mixed-duct IPMN(13),
      increased cyst size(7) and other(4). CONCLUSION: The prognosis of HGD-IPMN
      following resection is good; however, HGD may be a marker for developing IPMN
      recurrence or adenocarcinoma. Current guidelines regarding surgical indications
      for IPMN can miss a significant number of patients with HGD.

PMID- 28495435
TI  - Validation of clinical risk score for colorectal liver metastases resected in a
      contemporary multicenter cohort.
AB  - BACKGROUND: Recent advances in care for colorectal liver metastases (CRLM) have
      lengthened 5-year survival. In this new era, prognostic tools such as the
      clinical risk score (CRS) for colorectal liver metastases require reevaluation.
      METHODS: Patients undergoing resection for CRLM between 2008 and 2012 at 4
      specialty hepatobiliary centers in Canada (N = 740) were stratified by CRS and
      analyzed in Kaplan-Meier survival curves. Primary outcome of overall survival
      (OS) and secondary outcome of recurrence-free survival (RFS). Multivariate Cox
      regression compared CRS to patient factors. RESULTS: Median OS not reached (>60
      months), median RFS 16 months. Original CRS strata was a significant (p < 0.001)
      predictor of both OS (5-year OS: 0; 75%, 1; 71%, 2; 57%, 3; 57%, 4; 46%) and RFS
      (5-year RFS: 0; 39%, 1; 33%, 2; 21%, 3; 21%, 4; 8%). The presence of extrahepatic
      colorectal metastatic disease increased recurrence risk (RFS hazard ratio of 1.32
      (1.06-1.65)), and the use of intraoperative portal pedicle clamping reduced
      recurrence risk (RFS hazard ratio of 0.78 (0.61-0.99)). CONCLUSIONS: The CRS
      remains a relevant tool for predicting long-term outcomes for patients undergoing
      resection of CRLM. Additional factors such as the presence of extrahepatic
      colorectal metastatic disease and the use of intraoperative portal pedicle
      clamping may improve the prognostic power of the CRS.

PMID- 28495436
TI  - Factors relevant to persistent upper abdominal pain after cholecystectomy.
AB  - BACKGROUND: Cholecystectomy is a routine procedure for treatment of upper
      abdominal pain (UAP) and other atypical symptoms associated with gallstones. UAP,
      however, persists in some cases postoperatively. The present study was to
      identify the risk factors relevant to persistent UAP after cholecystectomy.
      METHODS: 1714 symptomatic patients undergoing cholecystectomy for gallstones were
      enrolled. All the patients were asked to complete a biliary symptom
      questionnaire. The risk factors for persistent postcholecystectomy UAP and
      features related to sustained relief of postcholecystectomy UAP were evaluated.
      RESULTS: 172 (10%) patients complained UAP after cholecystectomy. In multivariate
      analysis, female gender, preoperative UAP occurring >24h before admission, and
      each episode of UAP >30min were independently associated with persistent
      postoperative UAP (all p < 0.05). 132 (76.7%) patients reported sustained relief
      of postcholecystectomy UAP, the causes of which remained unknown but were
      attributed to functional postcholecystectomy syndrome. Shorter duration of
      preoperative UAP (occurring within 24 h before admission), less frequency of
      postoperative UAP (<=1 episode per day) and administration of choleretic
      medications were independently associated with postoperative UAP relief (all p <
      0.05). CONCLUSION: Females with longer historical and more frequent preoperative
      UAP are more likely to develop postcholecystectomy UAP. Choleretic medications
      are effective in relieving postoperative UAP.

PMID- 28495437
TI  - Case-controlled study comparing peri-operative and cancer-related outcomes after
      major hepatectomy and parenchymal sparing hepatectomy for metastatic colorectal
      cancer.
AB  - INTRODUCTION: Liver resection is potentially curative in selected patients with
      colorectal liver metastases (CLM). There has been a trend towards parenchyma
      sparing hepatectomy (PSH) rather than major hepatectomy (MH) due to lower
      perioperative morbidity. Although data from retrospective series suggest that
      long-term survival after PSM are similar to MH, these reports may be subject to
      selection bias. The aim of this study was to compare outcomes of PSH and MH in a
      case-controlled study. PATIENTS AND METHODS: 917 consecutive patients who
      underwent liver resection for CLM during 2000-2010 were identified from a
      prospective database. 238 patients who underwent PSH were case-matched with 238
      patients who had MH, for age, gender, tumour number, maximum tumour diameter,
      primary Dukes' stage, synchronicity and chemotherapy status using a propensity
      scoring system. Peri-operative outcomes, recurrence and long-term survival were
      compared. RESULTS: Fewer PSH patients received peri-operative blood transfusions
      (p < 0.0001). MH patients had greater incidence of complications (p = 0.04),
      grade III/IV complications (p = 0.01) and 90-day mortality (p = 0.03). Hospital
      stay was greater in the MH group (p = 0.04). There was no difference in
      overall/disease-free survival. CONCLUSION: Patients with resectable CLM should be
      offered PSH if technically feasible. PSH is safer than MH without compromising
      long-term survival.

PMID- 28495438
TI  - African Americans have a lower prevalence of portal vein thrombosis at the time
      of liver transplantation.
AB  - BACKGROUND: Perioperative vascular thrombotic events in patients undergoing liver
      transplantation (LT) are associated with significant morbidity and mortality.
      METHODS: In this retrospective UNOS database analysis, we evaluated the
      prevalence of portal vein thrombosis (PVT) and factors contributing to PVT
      development in different ethnic groups. RESULTS: Of the 47 953 LT performed
      between 2002 and 2015, we identified 3642 cases of PVT. African Americans (AA)
      had a significantly lower prevalence of PVT compared to other ethnic groups (p =
      0.0001). Multivariable regression analysis confirmed that AA were less likely
      than other ethnicities to have PVT (OR = 0.6). AA cohort was more likely to have
      infectious or autoimmune causes of liver failure (OR = 1.6, 1.7 respectively) as
      well as higher creatinine and INR compared to other groups (OR = 1.6, 1.3
      respectively). AA's were less likely to have encephalopathy, ascites, or variceal
      bleeding, which might indicate lower portal pressures. AA's were listed for LT
      later than other ethnicities and had both a lower functional status and higher
      MELD score at the time of registration. DISCUSSION: AA's had a significantly
      lower prevalence of preoperative PVT despite having a greater number of factors
      predisposing to thrombosis. This predisposition should be considered before
      instituting perioperative antithrombotic therapy.

PMID- 28495439
TI  - The impact of expanded indications on short-term outcomes for resection of
      malignant tumours of the liver over a 30 year period.
AB  - BACKGROUND: There are two philosophical approaches to planning liver resection
      for malignancy: one strives towards zero postoperative mortality by stringent
      selection of candidates, thus inherently limiting patients selected; the other,
      accepts a low yet definite postoperative mortality rate, and offers surgery to
      all those with potential gain in survival. The aim of this study was to
      retrospectively analyse an alternative and evolving strategy, and its impact on
      short-term outcomes. METHOD: 3118 consecutive hepatectomies performed in 2627
      patients over 3 decades (1980-2011) were analysed. Patient demographics, tumour
      characteristics, operative details, and postoperative outcomes were analysed.
      RESULTS: 1528 patients (58%) were male. Colorectal liver metastases (1221
      patients, 47%) and hepatocellular carcinoma (584 patients, 22%) were the most
      common diagnoses. Anatomical resections were performed in 2045 (66%), some form
      of vascular clamping was used in 2385 (72%), and blood transfusion was required
      in 1130 (36%) patients. Use of preoperative techniques to increase feasibility
      and safety of complex liver resections allowed expansion of indications to
      include sicker patients with larger tumours in the later period of the study.
      Overall morbidity and mortality rates were 31% and 3% respectively. During the
      first vs. second half of the study period the postoperative morbidity and
      mortality were 19% vs. 36% (p < 0.001) and 2% vs. 4% (p = 0.006) respectively.
      CONCLUSION: With increasing experience, more patients were accepted for complex
      hepatectomies. However, there was a definite yet contained increase in
      postoperative morbidity and mortality.

PMID- 28495441
TI  - Ventriculo-caval Shunt Migration.

PMID- 28495440
TI  - Corrigendum to 'Live birth derived from oocyte spindle transfer to prevent
      mitochondrial disease' [Reproductive BioMedicine Online 34 (2017) 361-368].

PMID- 28495442
TI  - Validation of plastic scintillation detectors for applications in low-dose-rate
      brachytherapy.
AB  - PURPOSE: To develop a plastic scintillation detector (PSD) capable of accurately
      measuring dose around a low-dose-rate (LDR) iodine-125 (125I) radioactive seed as
      a first step toward in vivo dosimetry for prostate LDR brachytherapy. METHODS:
      Using a GEANT4 based Monte Carlo code, photon energy distribution at any position
      around a realistic 125I source model was obtained. This energy distribution was
      convolved with the expected energy response from a plastic scintillator and
      dosimetry accuracy was evaluated. A PSD was constructed and validated in a water
      phantom for the entire range of clinically relevant positions around an 125I
      radioactive seed. RESULTS: The effect of energy dependence on dosimetry accuracy
      was shown to be limited, with a maximum relative difference of 1.2% from the
      calibration condition. A sophisticated approach to account for the energy
      dependence of PSDs is, therefore, not required if the detector is calibrated
      using the same model of radioactive seed or a geometrically similar one. The
      measurements were in good agreement with theoretical models for the entire
      clinical range. CONCLUSIONS: This study shows that PSDs can be used for accurate
      dosimetry in real time around a single 125I seed used in LDR prostate
      brachytherapy and is promising for clinical applications.

PMID- 28495443
TI  - Dose-volume correlation of cumulative vaginal doses and late toxicity after
      adjuvant external radiation and brachytherapy for cervical cancer.
AB  - PURPOSE: To investigate dose-response relationship between vaginal doses and long
      term morbidity. METHODS AND MATERIALS: Patients receiving adjuvant pelvic (chemo)
      radiation and brachytherapy for cervical cancer from January 2011 to December
      2014 were included. Baseline vaginal length was determined clinically and from
      imaging at BT planning. Dose points were defined along mucosa and at 5 mm depth
      at 12, 3, 6, and 9 'o' clock positions at every 2 cm from apex to introitus.
      Cumulative equivalent doses in 2 Gy were calculated. Vaginal stenosis was
      reported in reference to baseline length according to CTCAE version 3.0. Receiver
      operator characteristics curve was used to identify dose thresholds for
      univariate and multivariate analysis. RESULTS: Overall, 78 women with median age
      of 49 (32-71) years were included. The median dose at vaginal apex mucosa and 5
      mm depth was 118 Gy3 (78-198) and 81 Gy3 (70-149) respectively. At median follow
      up of 36 (18-60) months, vaginal stenosis >=25%, and grade >= II telangiectasia
      was observed in 33.3% and 45.7%, respectively. On receiver operator
      characteristics analysis, apical mucosal dose >142 Gy3 and recto-vaginal point
      dose >86 Gy3 predicted for stenosis on univariate (p = 0.02, p = 0.06) and
      multivariate analysis (p = 0.04). The probability of stenosis increased from 32%
      at 70 Gy3, 38% at 80 Gy3, and 45% at 90 Gy3 rectovaginal point dose. No
      correlation was observed between vaginal doses and telangiectasia and vaginal
      stenosis and sexual quality of life. CONCLUSION: Vaginal apex mucosal dose >142
      Gy3 independently predicts for vaginal stenosis.

PMID- 28495444
TI  - Comparing the RTOG/EORTC and LENT-SOMA scoring systems for the evaluation of late
      skin toxicity after 125I seed brachytherapy for parotid gland cancer.
AB  - PURPOSE: The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal
      Tissue Task Force-Subjective, Objective, Management and Analytic (LENT-SOMA)
      scoring systems were compared for grading late skin effects after iodine-125 seed
      brachytherapy in parotid gland cancer patients. METHODS AND MATERIALS: A total of
      109 patients diagnosed with parotid gland carcinoma were treated postoperatively
      with iodine-125 seed brachytherapy at a dose of 100-120 Gy. After 6-24 months of
      followup, telangiectasia, skin pigmentation, atrophy, fibrosis, and ulceration
      were scored according to both RTOG and LENT-SOMA scale criteria. The strength of
      correlation between the scores and the interobserver variability were calculated.
      RESULTS: Of 109 patients, 22.9% had telangiectasia; 78.9%, pigmentation; 28.4%,
      fibrosis; 4.6%, edema; 0.9%, ulceration; 37.6%, retraction and/or atrophy; 22.9%,
      sensation change; and 11%, scaliness and/or roughness. Compared with RTOG, LENT
      SOMA criteria resulted in the upgrading of pigmentation in 17% of cases, the
      downgrading of all instances of telangiectasia and the downgrading of one
      instance of Grade 4 ulceration to Grade 3. Between the two scales, fibrosis and
      atrophy correlated well (Spearman rho, 0.992, 0.986). An additional 229 side
      effects were observed using LENT-SOMA criteria. CONCLUSIONS: The LENT-SOMA scale
      was more accurate than the RTOG scale for the evaluation of late skin and
      subcutaneous toxicity. The downgrading of telangiectasia and upgrading of
      pigmentation with the LENT-SOMA scale reflected the patients' conditions better
      than the scores obtained with the RTOG scale. The assessment of fibrosis and
      atrophy correlated well between the two scales. The use of the sum of the
      individual scores of the LENT-SOMA is therefore advocated. The addition of
      decreased sweating and the removal of the alopecia (scalp) metric should be
      considered to standardize the reporting of late radiation morbidity.

PMID- 28495445
TI  - Preservation of von Willebrand factor multimers and function in patients with an
      EVAHEART centrifugal-type, continuous-flow left ventricular assist device.

PMID- 28495446
TI  - Mechanism of HRP-catalyzed nitrite oxidation by H2O2 revisited: Effect of
      nitroxides on enzyme inactivation and its catalytic activity.
AB  - The peroxidative activity of horseradish peroxidase (HRP) undergoes progressive
      inactivation while catalyzing the oxidation of nitrite by H2O2. The extent of
      inactivation increases as the pH increases, [nitrite] decreases or [H2O2]
      increases, and is accompanied by a loss of the Soret peak of HRP along with
      yellow-greenish coloration of the solution. HRP-catalyzed nitrite oxidation by
      H2O2 involves not only the formation of compounds I and II as transient heme
      species, but also compound III, all of which in turn, oxidize nitrite yielding
      *NO2. The rate constant of nitrite oxidation by compound III is at least 10-fold
      higher than that by compound II, which is also reducible by *NO2 where its
      reduction by nitrite is the rate-determining step of the catalytic cycle. The
      extent of the loss of the Soret peak of HRP is lower than the loss of its
      peroxidative activity implying that deterioration of the heme moiety leading to
      iron release only partially contributes toward heme inactivation. Cyclic stable
      nitroxide radicals, such as 2,2,6,6-tetramethyl-piperidine-N-oxyl (TPO), 4-OH-TPO
      and 4-NH2-TPO at uM concentrations detoxify *NO2 thus protecting HRP against
      inactivation mediated by this radical. Hence, HRP inactivation proceeds via
      nitration of the porphyrin ring most probably through compound I reaction with
      *NO2, which partially leads to deterioration of the heme moiety. The nitroxide
      acts catalytically since its oxidation by *NO2 yields the respective oxoammonium
      cation, which is readily reduced back to the nitroxide by H2O2, superoxide ion
      radical, and nitrite. In addition, the nitroxide catalytically inhibits tyrosine
      nitration mediated by HRP/H2O2/nitrite reactions system as it efficiently
      competes with tyrosyl radical for *NO2. The inhibition by nitroxides of tyrosine
      nitration is demonstrated also in the case of microperoxidase (MP-11) and
      cytochrome c revealing an additional role played by nitroxide antioxidants.

PMID- 28495447
TI  - Characterization of gene expression associated with the adaptation of the
      nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected
      function of the neuroglobin GLB-5 in innate immunity.
AB  - Oxygen (O2) is a double-edged sword to cells, for while it is vital for energy
      production in all aerobic animals and insufficient O2 (hypoxia) can lead to cell
      death, the reoxygenation of hypoxic tissues may trigger the generation of
      reactive oxygen species (ROS) that can destroy any biological molecule. Indeed,
      both hypoxia and hypoxia-reoxygenation (H/R) stress are harmful, and may play a
      critical role in the pathophysiology of many human diseases, such as myocardial
      ischemia and stroke. Therefore, understanding how animals adapt to hypoxia and
      H/R stress is critical for developing better treatments for these diseases.
      Previous studies showed that the neuroglobin GLB-5(Haw) is essential for the fast
      recovery of the nematode Caenorhabditis elegans (C. elegans) from H/R stress.
      Here, we characterize the changes in neuronal gene expression during the
      adaptation of worms to hypoxia and recovery from H/R stress. Our analysis shows
      that innate immunity genes are differentially expressed during both adaptation to
      hypoxia and recovery from H/R stress. Moreover, we reveal that the prolyl
      hydroxylase EGL-9, a known regulator of both adaptation to hypoxia and the innate
      immune response, inhibits the fast recovery from H/R stress through its activity
      in the O2-sensing neurons AQR, PQR, and URX. Finally, we show that GLB-5(Haw)
      acts in AQR, PQR, and URX to increase the tolerance of worms to Pseudomonas
      aeruginosa pathogenesis. Together, our studies suggest that innate immunity and
      recovery from H/R stress are regulated by overlapping signaling pathways.

PMID- 28495449
TI  - Peripheral circulatory disorders in essential thrombocythemia.
AB  - A significant number of patients with essential thrombocythemia (ET) complain of
      symptoms including distal parts of the extremities (e.g., paresthesias or
      Raynaud's phenomenon). The aim of the present study was to examine peripheral
      circulation in the upper extremities of individuals with ET. The study included
      45 ET patients and 30 control subjects. All participants were subjected to
      thermography, photoplethysmography, impedance plethysmography, and applanation
      tonometry pulse wave analysis. The patients with ET differed significantly from
      the control subjects in terms of 3rd finger skin temperature (mean 31.04 vs.
      32.45 degrees C), skin temperature gradient (mean 1.82 vs. 0.11 degrees C),
      photoplethysmographic amplitude (median 0.25 vs. 0.74%), and pulse waveform in
      the radial artery (more frequent occurrence of type B waveform). Pulse wave
      parameters correlated with the skin temperature gradient. The study findings
      imply the altered regulation of peripheral circulation in ET, including a
      decreased flow and an increased resistance.

PMID- 28495448
TI  - Nrf2 in keratinocytes modulates UVB-induced DNA damage and apoptosis in
      melanocytes through MAPK signaling.
AB  - Responses of melanocytes (MC) to ultraviolet (UV) irradiation can be influenced
      by their neighbouring keratinocytes (KC). We investigated the role of Nrf2 in
      regulating paracrine effects of KC on UVB-induced MC responses through
      phosphorylation of MAPKs in association with oxidative stress in primary human MC
      cocultured with primary human KC using a transwell co-culture system and small
      interfering RNA-mediated silencing of Nrf2 (siNrf2). The mechanisms by which Nrf2
      modulated paracrine factors including alpha-melanocyte-stimulating hormone (alpha
      MSH) and paracrine effects of KC on UVB-mediated apoptosis were also assessed.
      Our findings showed that co-culture of MC with siNrf2-transfected KC enhanced UVB
      mediated cyclobutane pyrimidine dimer (CPD) formation, apoptosis and oxidant
      formation, together with phosphorylation of ERK, JNK and p38 in MC. Treatment of
      MC with conditioned medium (CM) from Nrf2-depleted KC also increased UVB-mediated
      MC damage, suggesting that KC modulated UVB-mediated MC responses via paracrine
      effects. Additionally, depletion of Nrf2 in KC suppressed UVB-induced alpha-MSH
      levels as early as 30min post-irradiation, although pretreatment with N
      acetylcysteine (NAC) elevated its levels in CM from siNrf2-transfected KC.
      Furthermore, NAC reversed the effect of CM from Nrf2-depleted KC on UVB-induced
      apoptosis and inflammatory response in MC. Our study demonstrates for the first
      time that KC provided a rescue effect on UVB-mediated MC damage, although
      depletion of Nrf2 in KC reversed its protective effects on MC in a paracrine
      fashion in association with elevation of ROS levels and activation of MAPK
      pathways in MC. Nrf2 may indirectly regulate the paracrine effects of KC probably
      by affecting levels of the paracrine factor alpha-MSH via a ROS-dependent
      mechanism.

PMID- 28495450
TI  - Rho guanine nucleotide exchange factor (RGNEF) is a prosurvival factor under
      stress conditions.
AB  - Rho guanine nucleotide exchange factor (RGNEF) is a 190kDa RNA binding protein
      (RBP) that also contains a Dbl/PH domain capable of RhoA activation. Consistent
      with a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), RGNEF
      forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor
      neurons. To further understand the role of RGNEF in the stress response, we first
      observed that the expression of RGNEF is upregulated in murine spinal motor
      neurons following distal sciatic nerve injury. Secondly, in response to in vitro
      cellular stress (500MUM sodium arsenite for 1h; or 400mM sorbitol 1 hour
      exposure; as an oxidative or osmotic stress, respectively), we observed a
      significant survival benefit in RGNEF-transfected HEK293T cells. Using deletion
      constructs, we found that the NH2-terminus domain is essential for this
      protective effect. Interestingly, we observed that under stress conditions RGNEF
      associates with Staufen1 positive granules but not TIA-1-positive stress
      granules. These findings support the hypothesis that RGNEF plays a critical role
      both in RNA homeostasis and in the response to cell stress.

PMID- 28495451
TI  - Comparison of Image Quality and Diagnostic Performance of Cone-Beam CT during
      Drug-Eluting Embolic Transarterial Chemoembolization and Multidetector CT in the
      Detection of Hepatocellular Carcinoma.
AB  - PURPOSE: To compare image quality and diagnostic performance of cone-beam
      computed tomography (CT) and multidetector CT in the detection of hypervascular
      hepatocellular carcinoma (HCC) in patients with cirrhosis undergoing
      transarterial chemoembolization with drug-eluting embolic agents. MATERIALS AND
      METHODS: Fifty-five consecutive patients referred for chemoembolization of
      hypervascular HCC were prospectively enrolled. Imaging included preprocedural
      multidetector CT within 1 month before planned treatment, intraprocedural cone
      beam CT, and 1-month follow-up multidetector CT. Analysis of image quality was
      performed with calculations of lesion-to-liver contrast-to-noise ratio (LLCNR)
      and lesion-to-liver signal-to-noise-ratio (LLSNR). One-month follow-up
      multidetector CT was considered the reference standard for the detection of HCC
      nodules. RESULTS: Median LLCNR values were 3.94 (95% confidence interval [CI],
      3.06-5.05) for preprocedural multidetector CT and 6.90 (95% CI, 5.17-7.77) for
      intraprocedural cone-beam CT (P < .0001). Median LLSNR values were 11.53 (95% CI,
      9.51-12.44) for preprocedural multidetector CT and 9.36 (95% CI, 8.12-10.39) for
      intraprocedural cone-beam CT (P < .0104). Preprocedural multidetector CT detected
      115 hypervascular nodules with typical HCC behavior, and cone-beam CT detected 15
      additional hypervascular nodules that were also visible on 1-month follow-up
      multidetector CT. CONCLUSIONS: Cone-beam CT has a significantly higher diagnostic
      performance compared with preprocedural multidetector CT in the detection of HCCs
      and can influence management of patients with cirrhosis by identifying
      particularly aggressive tumors.

PMID- 28495452
TI  - Society of Interventional Radiology Position Statement on Parental Leave.

PMID- 28495453
TI  - Relative Initial Weight Is Associated with Improved Survival without Altering
      Tumor Latency in a Translational Rat Model of Diethylnitrosamine-Induced
      Hepatocellular Carcinoma and Transarterial Embolization.
AB  - PURPOSE: To test the hypotheses that (i) heavier rats demonstrate improved
      survival with diminished fibrosis in a diethylnitrosamine (DEN)-induced model of
      hepatocellular carcinoma (HCC) and (ii) transarterial embolization via femoral
      artery access decreases procedure times versus carotid access. MATERIALS AND
      METHODS: One hundred thirty-eight male Wistar rats ingested 0.01% DEN in water ad
      libitum for 12 weeks. T2-weighted magnetic resonance imaging was used for tumor
      surveillance. Rats underwent selective embolization of >= 5 mm tumors via carotid
      or femoral artery catheterization under fluoroscopic guidance. Rats were
      retrospectively categorized into 3 groups by initial weight (< 300, 300-400, >
      400 g) for analyses of survival, tumor latency, and fibrosis. Access site was
      compared relative to procedural success, mortality, and time. RESULTS: No
      significant differences in tumor latency were related to weight group (P = .310).
      Rats weighing < 300 g had shorter survival than both heavier groups (mean, 88 vs
      108 d; P < .0001), and more severe fibrosis (< 300 g median, 4.0; 300-400 g
      median, 1.5; > 400 g median, 1.0; P = .015). No significant difference was found
      in periprocedural mortality based on access site; however, procedure times were
      shorter via femoral approach (mean, 71 +/- 23 vs 127 +/- 24 min; P < .0001).
      CONCLUSIONS: Greater initial body weight resulted in improved survival without
      prolonged tumor latency for rats with DEN-induced HCCs and was associated with
      less severe fibrosis. A femoral approach for embolization resulted in decreased
      procedure time. These modifications provide a translational animal model of HCC
      and transarterial embolization that may be suited for short-term survival
      studies.

PMID- 28495454
TI  - Intratesticular and incisional line infiltration with ropivacaine for castration
      in medetomidine-butorphanol-midazolam sedated dogs.
AB  - OBJECTIVE: To evaluate whether intratesticular and incisional ropivacaine
      infiltration produces sufficient intra- and postoperative analgesia for
      castrating dogs under sedation. STUDY DESIGN: Randomized, blinded, controlled
      clinical study. ANIMALS: Twenty-three healthy dogs weighing 5.8-35.6 kg admitted
      for castration. METHODS: Dogs were sedated with medetomidine (0.01 mg kg-1),
      butorphanol (0.2 mg kg-1) and midazolam (0.2 mg kg-1) intramuscularly, and were
      randomly assigned to group R, 0.2-0.4 mL kg-1 of ropivacaine 0.5%, or group S, an
      equivalent volume of saline injected intratesticularly and along the incision
      line. If persistent motion was observed during surgery, sedation was considered
      to be insufficient and general anaesthesia was induced. Carprofen 2.2 mg kg-1 was
      administered postoperatively. Pain was evaluated in all dogs before sedation and
      postoperatively following atipamezole administration at 1, 2, 4, 8 and 24 hours
      using an interactive visual analogue scale (IVAS; 0-100), the Glasgow composite
      pain scale-short form (CMPS-SF; 0-24), and a mechanical algometer. Methadone 0.3
      mg kg-1 was administered intravenously to dogs if IVAS >30 or CMPS-SF >4.
      RESULTS: There was no significant difference between groups for the number of
      dogs administered general anaesthesia. The time from the beginning of surgery to
      induction of general anaesthesia was significantly shorter [median (range)] in
      group S [6 (3-25) minutes] than in group R [56 (36-76) minutes]. At 8 hours IVAS
      was significantly higher in group S (14 +/- 10) than in group R (6 +/- 4).
      CONCLUSIONS AND CLINICAL RELEVANCE: Intratesticular and incisional ropivacaine
      infiltration delayed the time to anaesthesia induction, and provided analgesia
      after castration performed under deep sedation in dogs. Intratesticular local
      anaesthesia can be an important part of the anaesthetic plan for castration.

PMID- 28495455
TI  - Increased Left Ventricular Diastolic Stiffness Is Associated With Heart Failure
      Symptoms in Aortic Stenosis Patients With Preserved Ejection Fraction.
AB  - BACKGROUND: Clinical risk factors associated with heart failure (HF) symptoms in
      aortic stenosis (AS) patients with preserved ejection fraction (EF) have not been
      fully identified. We hypothesized that left ventricular (LV) diastolic stiffness
      is associated with HF symptoms in patients with AS. METHODS AND RESULTS: We
      retrospectively evaluated 275 patients with at least moderate AS (aortic valve
      area <1.5 cm2) and preserved EF (>=50%). LV diastolic stiffness was evaluated
      with the use of echocardiographic parameters, diastolic wall strain (DWS, a
      measure of LV wall stiffness), and KLV (a marker of LV chamber stiffness). There
      were 69 patients with HF. Patients with HF were older, were more likely to be
      African American, had a higher body mass index, and had more hypertension and
      coronary artery disease (P < .05 for all). Aortic valve area index and mean
      pressure gradient across the aortic valve were not different between patients
      with and without HF. Despite similar echocardiographic parameters of AS severity,
      patients with HF had stiffer LV (DWS 0.21 +/- 0.06 vs 0.25 +/- 0.06 [P < .01],
      KLV 0.17 +/- 0.11 vs 0.13 +/- 0.08 [P < .01]). Logistic regression analyses
      revealed that after adjusting for age, race, body mass index, history of
      hypertension, and coronary artery disease, LV diastolic stiffness parameters
      remained significantly associated with HF symptoms. CONCLUSIONS: LV diastolic
      stiffness is independently associated with HF in AS patients with preserved EF.

PMID- 28495457
TI  - Effects of arsenic on adipocyte metabolism: Is arsenic an obesogen?
AB  - The environmental obesogen model proposes that in addition to a high-calorie diet
      and diminished physical activity, other factors such as environmental pollutants
      and chemicals are involved in the development of obesity. Although arsenic has
      been recognized as a risk factor for Type 2 Diabetes with a specific mechanism,
      it is still uncertain whether arsenic is also an obesogen. The impairment of
      white adipose tissue (WAT) metabolism is crucial in the onset of obesity, and
      distinct studies have evaluated the effects of arsenic on it, however only in
      some of them for obesity-related purposes. Thus, the known effects of arsenic on
      WAT/adipocytes were integrated based on the diverse metabolic and physiological
      processes that occur in WAT and are altered in obesity, specifically: adipocyte
      growth, adipokine secretion, lipid metabolism, and glucose metabolism. The
      currently available information suggests that arsenic can negatively affect WAT
      metabolism, resulting in arsenic being a potential obesogen.

PMID- 28495456
TI  - Crosstalk between STAT5 activation and PI3K/AKT functions in normal and
      transformed mammary epithelial cells.
AB  - Janus kinases (JAKs) and signal transducers and activators of transcription
      (STATs) have been shown to function downstream of several peptide hormones and
      cytokines that are required for postnatal development and secretory function of
      the mammary gland. As part of an extended network, these signal transducers can
      engage in crosstalk with other pathways to facilitate synergistic, and sometimes
      antagonistic, actions of different growth factors. Specifically, signaling
      through the JAK2/STAT5 cascade has been demonstrated to be indispensable for the
      specification, proliferation, differentiation, and survival of secretory mammary
      epithelial cells. Following a concise description of major cellular programs in
      mammary gland development and the role of growth factors that rely on JAK/STAT
      signaling to orchestrate these programs, this review highlights the significance
      of active STAT5 and its crosstalk with the PI3 kinase and AKT1 for mediating the
      proliferation of alveolar progenitors and survival of their functionally
      differentiated descendants in the mammary gland. Based on its ability to provide
      self-sufficiency in growth signals that are also capable of overriding intrinsic
      cell death programs, persistently active STAT5 can serve as a potent oncoprotein
      that contributes to the genesis of breast cancer. Recent experimental evidence
      demonstrated that, similar to normal developmental programs, oncogenic functions
      of STAT5 rely on molecular crosstalk with PI3K/AKT signaling for the initiation,
      and in some instances the progression, of breast cancer. The multitude by which
      STATs can interact with individual mediators of the PI3K/AKT signaling cascade
      may provide novel avenues for targeting signaling nodes within molecular networks
      that are crucial for the survival of cancer cells.

PMID- 28495458
TI  - Demonstration of a bronchobiliary fistula using magnetic resonance image with
      hepatospecific contrast agent.
AB  - Bronchobiliary fistulas are a rare entity of difficult diagnosis. The utility of
      magnetic resonance image (MRI) with hepatospecific contrast agents to demonstrate
      such condition is seldom described in the literature. This case reports a patient
      with pulmonary infection with a past history of hepatic surgery for hydatid
      disease in whom the presence of bile in the sputum rose the suspicious of a
      bronchobiliary fistula. MRI with hepatospecific contrast agents showed the
      communication between the biliary and bronchial tree and provided anatomic data
      to allow a therapeutic approach.

PMID- 28495459
TI  - Anaphylactic shock secondary to ruptured hydatid cyst of liver into the pleural
      cavity.

PMID- 28495460
TI  - Dual-energy computed tomography for the detection of focal liver lesions.
AB  - OBJECTIVE: To qualitatively and quantitatively explore the spectral study of
      focal liver lesions, comparing it with the usual polychromatic assessment with
      single-energy computed tomography. MATERIAL AND METHODS: We prospectively studied
      50 patients with at least one focal liver lesion who were referred for abdominal
      multidetector computed tomography with intravenous contrast material. The portal
      phase was acquired with dual energy sources. The density of the lesions and of
      the surrounding liver parenchyma was measured both in the baseline polychromatic
      acquisition and in the posterior monochromatic reconstructions at 40 keV, 70 keV,
      and 140 keV. Spectral curves were traced and the dual-energy indices and contrast
      to-noise ratio were calculated. Lastly, the quality of the images and the
      detectability of the lesions were assessed qualitatively. RESULTS: Densitometric
      differences between the different types of lesions (avascular and vascularized)
      and the liver were greater at low energy levels (left side of the spectral curve)
      than in the polychromatic evaluation. In the subjective assessment, the 40keV
      energy level had the greatest lesion detectability. CONCLUSIONS: Monochromatic
      spectral study with dual-energy computed tomography provides better lesion
      detectability at 40keV compared to that provided by the ordinary polychromatic
      evaluation.

PMID- 28495461
TI  - [Placental metastasis of breast adenocarcinoma].

PMID- 28495462
TI  - Birth preference in women undergoing treatment for childbirth fear: A randomised
      controlled trial.
AB  - BACKGROUND: Childbirth fear is the most common underlying reason for requesting a
      caesarean section without medical reason. The aim of this randomised controlled
      study was to investigate birth preferences in women undergoing treatment for
      childbirth fear, and to investigate birth experience and satisfaction with the
      allocated treatment. METHODS: Pregnant women classified with childbirth fear
      (>=60 on the Fear Of Birth Scale) (n=258) were recruited at one university
      hospital and two regional hospitals over one year. The participants were
      randomised (1:1) to intervention (Internet-based Cognitive Behaviour Therapy
      (ICBT)) (n=127) or standard care (face-to-face counselling) (n=131). Data were
      collected by questionnaires in pregnancy week 20-25 (baseline), week 36 and two
      months after birth. RESULTS: Caesarean section preference decreased from 34% to
      12% in the ICBT group and from 24% to 20% in the counselling group. Two months
      after birth, the preference for caesarean increased to 20% in the ICBT group and
      to 29% in the counselling group, and there was no statistically significant
      change over time. Women in the ICBT group were less satisfied with the treatment
      (OR 4.5). The treatment had no impact on or worsened their childbirth fear (OR
      5.5). There were no differences between the groups regarding birth experience.
      CONCLUSION: Women's birth preferences fluctuated over the course of pregnancy and
      after birth regardless of treatment method. Women felt their fear was reduced and
      were more satisfied with face-to-face counselling compared to ICBT. A higher
      percentage were lost to follow-up in ICBT group suggesting a need for further
      research.

PMID- 28495463
TI  - Development of an animal model of progressive vaccinia in nu/nu mice and the use
      of bioluminescence imaging for assessment of the efficacy of monoclonal
      antibodies against vaccinial B5 and L1 proteins.
AB  - Bioluminescence imaging (BLI) was used to follow dissemination of recombinant
      vaccinia virus (VACV) expressing luciferase (IHD-J-Luc) in BALB/c nu/nu mice
      treated post-challenge with monoclonal antibodies (MAbs) against L1 and B5 VACV
      proteins in a model of Progressive Vaccinia (PV). Areas Under the flux Curve
      (AUC) were calculated for viral loads in multiple organs in individual mice.
      Following scarification with 105 pfu, IHD-J-Luc VACV undergoes fast replication
      at the injection site and disseminates rapidly to the inguinal lymph nodes
      followed by spleen, liver, and axillary lymph nodes within 2-3 days and before
      primary lesions are visible at the site of scarification. Extension of survival
      in nude mice treated with a combination of anti-B5 and anti-L1 MAbs 24 h post
      challenge correlated with a significant reduction in viral load at the site of
      scarification and delayed systemic dissemination. Nude mice reconstituted with
      104 T cells prior to challenge with IHD-J-Luc, and treated with MAbs post
      challenge, survived infection, cleared the virus from all organs and
      scarification site, and developed anti-VACV IgG and VACV-specific polyfunctional
      CD8+ T cells that co-expressed the degranulation marker CD107a, and IFNgamma and
      TNFalpha cytokines. All T cell reconstituted mice survived intranasal re
      challenge with IHD-J-Luc (104 pfu) two months after the primary infection. Thus,
      using BLI to monitor VACV replication in a PV model, we showed that anti-VACV
      MAbs administered post challenge extended survival of nude mice and protected T
      cell reconstituted nude mice from lethality by reducing replication at the site
      of scarification and systemic dissemination of VACV.

PMID- 28495464
TI  - MicroRNA-21 via Dysregulation of WW Domain-Containing Protein 1 Regulate Atrial
      Fibrosis in Atrial Fibrillation.
AB  - BACKGROUND: microRNAs (miRs) have been reported to regulate cell biological
      functions. To explore the underlying mechanism of miR-21 involvement in patients
      with atrial fibrosis and atrial fibrillation (AF). METHODS: In total, 49 patients
      (24 AF, sinus rhythm 25) aged 33-68 years old, including heart valve replacement
      surgery and cardiac catheterisation. The pathological changes and collagen
      depositions was analysed by Masson's Trichrome Staining. miR-21, TGF-beta1,
      Smad2, p-Smad2, WWP-1, collagen I and collagen III expression were analysed by
      Western blotting, qRT-PCR, miR one step qRT-PCR, respectively. Treatment human
      cardiac fibroblasts with TGF-beta1, qRT-PCR and Western blotting to find changes
      in miR-21, Smad2 and WWP-1 levels. Transfected human cardiac fibroblasts with miR
      21 mimic and miR-21 inhibitor. Finally, cell proliferation ability was assessed
      by the MTT assay and flow cytometry. RESULTS: Compared to sinus rhythm (SR)
      group, the collagen volume fraction was significantly increased in AF patients.
      The levels of the TGF-beta1, collagen I and collagen III were significantly
      elevated in AF group. In AF patients, the expression of miR-21 was increased,
      while the expression of WWP-1 was decreased. Transfected cardiac fibroblasts with
      miR-21 mimic increased miR-21 expression and decreased WWP-1 expression, whereas
      miR-21 inhibitor causes the opposite effects. Additionally, we demonstrated that
      knockdown miR-21 targeted up-regulation of WWP-1 may suppress cardiac fibroblasts
      proliferation. CONCLUSION: These indicated that miR-21 inhibits cardiac
      fibroblasts proliferation by inactivating the TGF-beta1/Smad2 signaling pathway
      via up-regulation of WWP-1.

PMID- 28495465
TI  - The effect of blue-enriched white light on cognitive performances and sleepiness
      of night-shift workers: A field study.
AB  - INTRODUCTION: Night-shift works are basically accompanied by reduced cognitive
      performance, sleepiness, and higher possibility for human error and related
      incidents. It is therefore crucial to improve individuals' performance and
      alertness in sensitive places like industries' control room with the ultimate
      goal of increasing efficiency and reducing the number of possible incidents.
      Previous research has indicated that blue light is a critical cue for entraining
      circadian rhythm. As a result, the present study was an attempt to investigate
      whether blue-enriched white light illumination was a practical strategy to
      decrease sleepiness and improve cognitive performance during night shifts.
      MARTIAL AND METHODS: The study, which adopted a before-after interventional
      design, was conducted among 30 control room staff members of petrochemical
      industry. After baseline assessments under existing lighting conditions, every
      participant was exposed to two new lighting conditions (namely, 17,000K and 6500K
      blue-enriched white light), each lasting for a week. Assessments were conducted
      again at the end of these treatments. In order to measure the subjective
      sleepiness, Karolinska Sleepiness Scale (KSS) was utilized. Subjects also
      performed the Conners' Continuous Performance Test II (CPT-II) and 1-back test in
      order to gauge their cognitive performance, and melatonin assessment was carried
      out using salivary and Eliza technique. The data was analyzed using two-way
      repeated measure ANOVA. RESULTS: The results indicated that, compared to normal
      lighting conditions, participants' sleepiness and melatonin rhythm significantly
      declined when they were exposed to blue-enriched white light. Furthermore, the
      experimental condition had a significant effect on the reduction of working
      memory errors. It also decreased omission errors and the reaction time during the
      sustained attention task. CONCLUSIONS: Thus, using blue-enriched white light may
      be a proper ergonomic strategy for improving performance and alertness,
      especially during night, in sensitive environments like control rooms.

PMID- 28495466
TI  - Methicillin-resistant Staphylococcus aureus Screening PCR adapted to locally
      emerging variants-Evaluation of novel SCCmec primers.
AB  - Infections with multi-resistant bacteria, such as Methicillin-resistant
      Staphylococcus aureus (MRSA), represent a world-wide health-care problem. The
      original MRSA Screening TaqMan PCR was based on the detection of the SCCmec-orfX
      junction as described by the group of Huletsky in 2004. In the recent years, this
      assay increasingly failed to detect new MRSA variants in swab specimens. In this
      work, we analyzed the usefulness of 17 additional SCCmec primers to increase PCR
      sensitivity by testing 290 collected samples with negative PCR results and
      positive MRSA culture in a retrospective analysis, and 380 samples of the daily
      routine diagnostics. Sequencing of the PCR products revealed that locally new
      MRSA variants became detectable by nine of these forward primers. Four primers
      were solely responsible for the detection of 85.4% (117/123) of the PCR products:
      F13 (n=76), F11 (n=6), F14 (n=15) and F25 (n=8). These four primers were
      integrated in the Screening PCR and the novel primer collection was validated by
      testing 71 MRSA isolates, which covered SCCmec types I to VI, 50 MSSA isolates
      and 100 swab specimens. The sensitivity of MRSA Screening PCR increased from 93%
      to 98.6% without affecting the detection of the common MRSA strains. Phylogenetic
      analysis of the PCR products suggests that the adapted MRSA Screening PCR is able
      to detect SCCmec types I-X, including CA- and LA-MRSA variants by the SCCmec
      primers F11 and F25.

PMID- 28495467
TI  - Mobile Health Technology in Late-Life Mental Illness: A Focused Literature
      Review.
AB  - OBJECTIVE: In an era of rising geriatric mental health care needs worldwide,
      technological advances can help address care needs in a cost-effective fashion.
      Our objective in this review was to assess whether mobile health technology, such
      as tablets and smartphones, are feasible to use in patients with late-life mental
      and cognitive disorders, as well as whether they were generally reliable modes of
      mental health/cognitive assessment. METHODS: We performed a focused literature
      review of MEDLINE, PsychInfo, and Embase databases, including papers specifically
      assessing the implementation of mobile health technologies: electronic tablets
      (e.g., iPad), smartphones, and other mobile computerized equipment in older
      adults (age >=65 years) diagnosed with or at risk of a mental and/or cognitive
      disorder. RESULTS: A total of 2,079 records were assessed, of which 7 papers were
      of direct relevance. Studies investigated a broad variety of mobile health
      technologies. Almost all examined samples with dementia/cognitive dysfunction or
      at risk for those disorders. All studies exclusively examined the use of mobile
      health technologies for the assessment of cognitive and or mental illness
      symptoms or disorders. None of the studies reported participants having any
      difficulties using the mobile health technology assessments and overall
      reliability was similar to paper-and-pencil modes of assessment. CONCLUSION:
      Overall, mobile health technologies were found to be feasible by patients and had
      promising reliability for the assessment of cognitive and mental illness domains
      in older adults. Future clinical trials will be necessary to assess whether
      portable communication interventions (e.g., symptom tracking) can improve
      geriatric mental health outcomes.

PMID- 28495468
TI  - Commentary for "Steeper Slope of Age-Related Changes in White Matter
      Microstructure and Processing Speed in Bipolar Disorder".

PMID- 28495469
TI  - Clock Copying Predicts Mortality in Adult Protective Services Clients.
AB  - OBJECTIVE: The objective of this study was to determine if a clock copying task
      predicts 18-month mortality in an Adult Protective Services (APS) sample referred
      for a decision-making capacity assessment. METHODS: The authors performed a
      retrospective medical record review of clients (N = 233) referred by APS for a
      decision-making capacity assessment during a 3-year time period. Information
      extracted included demographic data and neuropsychological performance on a
      battery sensitive to executive function, visuospatial ability, depression,
      memory, and general cognition. A Cox proportional hazards models was constructed
      to determine the relationship between Executive Clock Drawing Task Part 2 (CLOX2)
      performance and survival. RESULTS: Poor clock copying, as measured by CLOX2,
      predicted 18-month mortality when covaried for age, education, sex, rural
      dwelling status, depression, and general cognition. CONCLUSIONS: Clock copying is
      an easily administered visuospatial task that may inform survival in this
      vulnerable population.

PMID- 28495471
TI  - Quantitative outcome measures for systemic sclerosis-related Microangiopathy -
      Reliability of image acquisition in Nailfold Capillaroscopy.
AB  - BACKGROUND: Nailfold capillaroscopic parameters hold increasing promise as
      outcome measures for clinical trials in systemic sclerosis (SSc). Their inclusion
      as outcomes would often naturally require capillaroscopy images to be captured at
      several time points during any one study. Our objective was to assess
      repeatability of image acquisition (which has been little studied), as well as of
      measurement. METHOD: 41 patients (26 with SSc, 15 with primary Raynaud's
      phenomenon) and 10 healthy controls returned for repeat high-magnification (300*)
      videocapillaroscopy mosaic imaging of 10 digits one week after initial imaging
      (as part of a larger study of reliability). Images were assessed in a random
      order by an expert blinded observer and 4 outcome measures extracted: (1) overall
      image grade and then (where possible) distal vessel locations were marked,
      allowing (2) vessel density (across the whole nailfold) to be calculated (3) apex
      width measurement and (4) giant vessel count. Intra-rater, intra-visit and intra
      rater inter-visit (baseline vs. 1week) reliability were examined in 475 and 392
      images respectively. A linear, mixed-effects model was used to estimate variance
      components, from which intra-class correlation coefficients (ICCs) were
      determined. RESULTS: Intra-visit and inter-visit reliability estimates (ICCs)
      were (respectively): overall image grade, 0.97 and 0.90; vessel density, 0.92 and
      0.65; mean vessel width, 0.91 and 0.79; presence of giant capillary, 0.68 and
      0.56. These estimates were conditional on each parameter being measurable.
      CONCLUSION: Within-operator image analysis and acquisition are reproducible.
      Quantitative nailfold capillaroscopy, at least with a single observer, provides
      reliable outcome measures for clinical studies including randomised controlled
      trials.

PMID- 28495472
TI  - Matrix-specific distribution and diastereomeric profiles of
      hexabromocyclododecane (HBCD) in a multimedia environment: Air, soil, sludge,
      sediment, and fish.
AB  - Hexabromocyclododecane (HBCD) contamination and its diastereomeric profile were
      investigated in a multi-media environment along a river at the local scale in
      air, soil, sludge, sediment, and fish samples. The spatial distribution of HBCD
      in each matrix showed a different result. The highest concentrations of HBCD in
      air and soil were detected near a general industrial complex; in the sediment and
      sludge samples, they were detected in the down-stream region (i.e., urban area).
      Each matrix showed the specific distribution patterns of HBCD diastereomers,
      suggesting continuous inputs of contaminants, different physicochemical
      properties, or isomerizations. The particle phases in air, sludge, and fish
      matrices were dominated by alpha-HBCD, owing to HBCD's various isomerization
      processes and different degradation rate in the environment, and metabolic
      capabilities of the fish; in contrast, the sediment and soil matrices were
      dominated by gamma-HBCD because of the major composition of the technical
      mixtures and the strong adsorption onto solid particles. Based on these results,
      the prevalent and matrix-specific distribution of HBCD diastereomers suggested
      that more careful consideration should be given to the characteristics of the
      matrices and their effects on the potential influence of HBCD at the
      diastereomeric level.

PMID- 28495470
TI  - Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults.
AB  - Advances in cancer treatment are producing a growing number of cancer survivors;
      therefore, issues surrounding quality of life during and following cancer
      treatment have become increasingly important. Chemotherapy-related cognitive
      impairment (CRCI) is a problem that is commonly reported following the
      administration of chemotherapy treatment in patients with cancer. Research
      suggests that CRCI can persist for months to years after completing treatment,
      which has implications for the trajectory of normal and pathologic cognitive
      aging for the growing number of long-term cancer survivors. These problems are
      particularly relevant for older individuals, given that cancer is largely a
      disease of older age, and the number of patients with cancer who are aged 65
      years or older will increase dramatically over the coming decades. This review
      will briefly summarize empirical findings related to CRCI, discuss CRCI in older
      patients with cancer, propose potential causative hypotheses, and provide a
      canonical patient case to illustrate how CRCI presents clinically. Finally,
      potential intervention strategies for CRCI will be highlighted and issues to
      consider when evaluating older patients with a history of cancer will be
      discussed.

PMID- 28495473
TI  - Genetic polymorphisms of the P2X7 gene associated with susceptibility to and
      prognosis of pulmonary tuberculosis.
AB  - In this population-based case control study, we recruited 1601 pulmonary
      tuberculosis cases and 1526 healthy controls, aiming to investigate the
      association of genetic polymorphisms of the P2X7 gene with the susceptibility to
      and prognosis of pulmonary tuberculosis in a Chinese Han population. Five single
      nucleotide polymorphisms (SNPs) in the P2X7 gene were genotyped. The odds ratio
      (OR) or relative risk (RR) together with 95% confidence interval (CI) were used
      to estimated the effect of genetic polymorphisms on the disease. After correction
      for multiple comparisons, the SNP rs1718119 remained significant. The allele A of
      rs1718119 was related to a reduced risk for all active tuberculosis (OR for each
      additional allele A: 0.81, 95% CI: 0.69-0.94) and sputum smear-positive cases (OR
      for each additional allele A: 0.78, 95% CI: 0.66-0.93). The effects of these
      genetic variations were more evident among smokers. Survival analysis showed a
      weak association between rs7958311 and treatment outcome, where each additional
      allele A of the SNP rs7958311 contributed to a 59% increase in the probability of
      a successful treatment outcome (adjusted RR: 1.59, 95% CI: 1.05-2.40, P=0.028);
      but it wasn't significant after the Bonferroni correction. We demonstrated that
      genetic variations of the P2X7 gene might be involved in the risk and prognosis
      of human tuberculosis.

PMID- 28495474
TI  - Late effect of developmental exposure to glycidol on hippocampal neurogenesis in
      mice: Loss of parvalbumin-expressing interneurons.
AB  - Developmental exposure to glycidol of rats causes axonal injury targeting axon
      terminals in dams and transient disruption of late-stage differentiation of
      hippocampal neurogenesis, accompanying sustained increase in the number of reelin
      producing or calretinin-expressing interneurons in offspring. The molecular
      mechanism of disruptive neurogenesis probably targets the newly generating nerve
      terminals. We previously found differences between mice and rats in the effects
      on hippocampal neurogenesis after developmental exposure to the same neurotoxic
      substances. In the present study, we examined the effects and underlying
      mechanisms of developmental exposure to glycidol on hippocampal neurogenesis in
      mice. Glycidol (800 or 1600ppm) was administered in drinking water to mated
      female mice from gestational day 6 to postnatal day 21. Compared to mice drinking
      water without glycidol (control), the exposed dams showed axon terminal injury at
      both concentrations of glycidol. The offspring of the dams that had received
      1600ppm glycidol had fewer parvalbumin (PVALB)+ gamma-aminobutyric acid (GABA)
      ergic interneurons and neuron-specific nuclear protein+ postmitotic neurons in
      the hilus of the hippocampal dentate gyrus. Thus, exposure of glycidol to adult
      mice induced axonal degeneration equivalent to that seen in the rat; however, the
      target mechanism for the disruption of hippocampal neurogenesis by developmental
      exposure was different from that in rats, with the hilar neuronal population not
      affected until adulthood. Considering the role of PVALB+ GABAergic interneurons
      in the brain, developmental glycidol exposure in mice may cause a decline in
      cognitive function in later life, and involve a different mechanism from that
      targeting axon terminals in rats.

PMID- 28495475
TI  - Ameliorative effects of Achillea millefolium inflorescences alcoholic extract
      against nicotine-induced reproductive failure in rat.
AB  - BACKGROUND: Nicotine (Nic) is a major risk factor in the development of
      functional disorders of male reproductive system. Achillea millefolium; is highly
      regarded for medicinal activities, due to its antioxidant and anti-inflammatory
      properties. This study was carried out to evaluate whether Achillea millefolium
      (Achm) inflorescences alcoholic extract could serve as a protective agent in male
      reproductive male failures during Nic exposure in a rat model. METHODS: Twenty
      five adult male Wistar rats were categorized into the five groups. Tests 1 and 3
      groups were received Nic at dose levels of 0.2 and 0.4mg/kg BW/day, respectively
      by IP injection. Tests 2 and 4 groups were received Nic at the same doses along
      with Achm at dose level of 120mg/kg BW/day. The study period took forty-eight
      days for all experimental groups. RESULTS: Nic groups showed significant
      decreases in tubule differentiation index (TDI), sperm count, motility,
      stereological parameters and an increase in dead and abnormal sperms. Moreover,
      the reduction in total antioxidant capacity (TAC), superoxide dismutase (SOD)
      activity, serum levels of FSH, LH and testosterone, along with increased serum
      concentration of LDH were observed in the Nic groups. Total nitrite and
      malondealdehyde levels increased and total thiol molecules (TTM) levels decreased
      in testicular tissue in the Nic groups. Notably, Achm co-administration caused a
      contemporary recovery in above-mentioned parameters. CONCLUSION: Nic exerts major
      toxicity in testicular tissue and causes damages in several ways including,
      oxidative stress, whilst Achm imposes protective effect against Nic-induced
      reproductive failure, which may attribute to its antioxidant capacity.

PMID- 28495476
TI  - Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease
      through metabolomics and hippocampal proteomics.
AB  - Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and
      treatment are not sufficient so far. The purpose of this study is to develop
      biomarkers and therapeutic targets for diagnosis and better understanding of AD.
      As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism
      including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and
      sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF
      MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including
      GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD
      hippocampus by using label free nano-LC-MS/MS. Thus, pathogenesis of AD was
      involved with increasing of choline, decreasing of ACh, enhancement of GSTs and
      increasing of glutamate which led to oxidative stress and excitotoxity. Effects
      of donepezil and a natural medicine were evaluated through metabolomics and
      proteomics. In summary, proteomic and metabolomic analysis on constructed AD rat
      model were performed through rapid, sensitive and high resolution LC-MS methods
      to reveal candidate biomarkers. The data suggested that GSTs have great value as
      therapeutic targets. This study provided valuable information for the diagnosis
      mechanism and drug discovery of AD.

PMID- 28495477
TI  - Quantification of saxitoxin in human blood by ELISA.
AB  - Saxitoxin (STX) is a potent marine toxin that causes paralytic shellfish
      poisoning (PSP) which can result in significant morbidity and mortality in
      humans. Low lethal doses, rapid onset of PSP symptoms, and brief STX half-life in
      vivo require sensitive and rapid diagnostic techniques to monitor human
      exposures. Our laboratory has validated an enzyme-linked immunosorbent assay
      (ELISA) for quantitative detection of STX from 0.020 to 0.80 ng/mL in human whole
      blood and from 0.06 to 2.0 ng/mL in dried human blood which is simple, sensitive,
      rapid, and cost-effective. To our knowledge, this is the first validated method
      for the quantitation of saxitoxin in whole blood. Microsampling devices were used
      in sample collection which allows for standardized collection of blood, stable
      storage, and cost-efficient shipping. Quality control precision and accuracy were
      evaluated over the course of validation and were within 20% of theoretical
      concentrations. No detectable background concentrations of STX were found among
      fifty whole blood and dried blood convenience samples. Additionally, ten spiked
      individual whole blood and dried blood samples were tested for accuracy and
      precision and were within 20% of theoretical concentrations. Gonyautoxins 2&3
      (GTX2&3) cross-reacted with this ELISA by 21%, but all other structurally related
      PSP toxins tested cross-reacted less than two percent. While clinical diagnosis
      or treatment of PSP would be unaffected by GTX2&3 cross-reactivity by ELISA, to
      accurately quantify individual PSP toxins, these results should be coupled with
      high performance liquid chromatography mass spectrometry measurements.

PMID- 28495479
TI  - Limited sampling strategies for determining the area under the plasma
      concentration-time curve for isoniazid might be a valuable approach for
      optimizing treatment in adult patients with tuberculosis.
AB  - This study aimed to develop clinically feasible models of limited sampling
      strategy (LSS) for estimation of the area under the concentration-time curve
      (AUC24h) for isoniazid, that could be applied easily in daily clinical practice
      for dosage adjustment in adult patients with tuberculosis. Isoniazid plasma
      concentrations (n = 1665) from 185 adult tuberculous patients were used for the
      development and validation of LSS models to estimate AUC24h following
      administration of the standard 5 mg/kg dose of isoniazid. Population
      pharmacokinetic analysis for appropriate estimation of isoniazid pharmacokinetic
      parameters was performed in a modelling group (n = 100). The Bayesian estimates
      of AUC24h (AUCref) obtained for each individual were used as the dependent
      variable in the regression analysis for the development of various LSS models.
      The LSS models were validated in a separate cohort (n = 85). Several three and
      four time point LSS models were built and tested. Model H (AUC24h = -1.88 + 1.05
      * C1 + 0.78 * C2 + 9.44 * C5) and Model I (AUC24h = -0.65 + 1.00 * C1 + 1.94 * C2
      + 15.45 * C9) had the best performances [adj-R2 = 0.93, median prediction error
      (MPE) = -0.20, root median squared prediction error (RMSE) = 4.65 for Model H;
      adj-R2 = 0.96, MPE = -0.05 RMSE = 3.56 for Model I]. The very high R2 values
      (>=0.94) of these regression equations in the validation cohort confirmed their
      high reliability. These LSS models could be applied in the context of therapeutic
      drug monitoring programmes aiming to personalize isoniazid dosing regimens for
      adult patients with tuberculosis.

PMID- 28495480
TI  - [Fabien Arcelin (1876-1942), or how to become a radiation oncologist when born an
      archeologist].
AB  - Fabien Arcelin, physician working in Lyon, pioneer of radiology and radiotherapy,
      was both mentored by Destot (one of the fathers of the French radiology for his
      thesis of medicine) and by his own father Adrien Arcelin (one of the two
      codiscoverers of the prehistorical site of the Roche-de-Solutre in Burgundy) for
      archeological works. Hence, radiologist in Lyon during the week and archeologist
      during the weekend, Fabien Arcelin made significant advances in both radiation
      research and archeology. He was notably the discoverer of the first tombs of
      Aurignacian men. In radiology, he examined about 2000 radiographic heart views
      with the Destot's orthodiagraph to assess the cardiothoracic ratio and wrote a
      reference book about the use of X-rays to detect kidney stones. He made the first
      survey about the secondary effects of radiotherapy, important database for
      pointing out individual radiosensitivity. In parallel to the radiotherapy trials
      of Regaud at Curie institute (Paris), he performed the first series of anticancer
      treatments in Lyon.

PMID- 28495478
TI  - Determinants of Sugar-Sweetened Beverage Consumption among Low-Income Children:
      Are There Differences by Race/Ethnicity, Age, and Sex?
AB  - BACKGROUND: Understanding determinants of high consumption of sugar-sweetened
      beverages (SSBs), a highly prevalent obesogenic behavior, will help build
      effective customized public health interventions. OBJECTIVE: Our aim was to
      identify child and parent lifestyle and household demographic factors predictive
      of high SSB consumption frequency in children from low-income, ethnically diverse
      communities that may help inform public health interventions. DESIGN: We used a
      cross-sectional telephone household survey. PARTICIPANTS/SETTING: Participants
      were 717 boys and 686 girls aged 3 to 18 years old from the New Jersey Childhood
      Obesity Study living in five low-income cities (Camden, New Brunswick, Newark,
      Trenton, and Vineland). The adult most knowledgeable about household food
      shopping completed a questionnaire over the telephone inquiring about their and
      their child's dietary and physical activity habits, and household-, parent-, and
      child-level demographics. MAIN OUTCOME MEASURES: Child's SSB consumption
      frequency was measured. STATISTICAL ANALYSIS PERFORMED: Multivariate ordered
      logit models were designed to investigate a variety of variables hypothesized to
      affect the frequency of SSB consumption. Exploratory stratified analyses by race,
      sex, and age were also conducted. RESULTS: Eight percent of our study
      participants never consumed SSBs, 45% consumed SSBs at least once per day, and
      23% consumed twice or more per day. SSB consumption was higher among children 12
      to 18 years vs 3 to 5 years (P<0.0001), of non-Hispanic black vs non-Hispanic
      white race/ethnicity (P=0.010), who were moderate fast food consumers vs never
      consumers (P=0.003), and those whose parents were high vs low SSB consumers
      (P<0.0001). Living in a non-English-speaking household (P=0.030), having a parent
      with a college or higher education vs less than high school (P=0.003), and having
      breakfast 6 to 7 days/wk vs never to 2 days/wk or less were associated with lower
      SSB consumption (P=0.001). CONCLUSIONS: We identified a number of household-,
      parent-, and child-level predictors of SSB consumption, which varied by race,
      sex, and age, useful for building customized interventions targeting certain
      behaviors in ethnically diverse, low-income children.

PMID- 28495481
TI  - Prediction of local control in early glottic carcinoma using the maximum
      standardised uptake value.
AB  - PURPOSE: This retrospective study aimed to determine whether the maximum
      standardised uptake value (SUVmax) can predict local tumour control in early
      glottic cancer (Tis, T1, and T2). PATIENTS AND METHODS: Fifty-nine patients
      treated with definitive radiotherapy for early glottic cancer between 2003 and
      2011 were enrolled. We evaluated the SUVmax in the region of interest around the
      original tumour site. Local tumour control and survival were estimated using
      Kaplan-Meier curves. Receiver operating characteristic curves were used to assess
      the optimal SUVmax cut-off for predicting local control. RESULTS: As determined
      by laryngoscopy, all patients achieved a complete response. Eleven patients
      experienced local recurrence, while no distant metastasis occurred. One patient
      died due to local recurrence, while five lost their larynxes. The median follow
      up was 61.5 (range: 6.2-123.4) months. The five-year local progression-free
      survival was 84.7%, and larynx preservation was possible in 89.6% of cases. The
      median SUVmax was 2.2. The optimal SUVmax for predicting local tumour control was
      identified as 3.4. Patients with glottic cancers with an SUVmax>3.4 showed a
      significantly lower local progression-free survival rate than those with tumours
      with an SUVmax<3.4 (five-year local progression-free survival rate: 53.4% vs.
      95.4%, P<0.01). Multivariate analysis confirmed that a high SUVmax was an
      independent predictive factor for local progression-free survival (P=0.006).
      CONCLUSION: The use of (18F)-fluorodeoxyglucose-positron emission tomography for
      evaluation of the SUVmax is useful to predict local progression-free survival in
      patients with early glottic cancer treated by radiation. Early glottic cancer
      with a high SUVmax may require aggressive local treatment and careful
      surveillance.

PMID- 28495483
TI  - Breast cancer: Is radiotherapy of internal mammary nodes the "state of the art"
      or "reheating the cold dish"? About a discussion, review of the literature and
      own opinion.

PMID- 28495482
TI  - [Recurrence of a glassy cell carcinoma of the vagina: An exceptional situation].
AB  - Glassy cell carcinoma is a rare neoplasm that occurs most frequently in the
      uterine cervix. We describe the second reported case of glassy cell carcinoma
      arising in the vagina. We present a case of a 24-year-old woman with a history of
      post-coital bleeding associated with menometrorrhagia. Different explorations
      have concluded in a glassy cell carcinoma arising in the vagina, with clinical
      staging III according to the International Federation of Obstetrics and
      Gynecology. The patient received three cycles of neoadjuvant chemotherapy with a
      good response. Then she had a para-aortic lymphadenectomy and ovarian
      transposition. Following the surgery, she had radiotherapy. The gynecological
      examination showed no budding lesion and the biopsy was negative. Six months
      later, the patient complained of a pelvic pain. The examination revealed a
      locoregional recurrence. Surgical revision was not possible and the patient was a
      candidate for a palliative chemotherapy. Although, glassy cell carcinoma runs an
      aggressive clinical course, an early diagnosis may help in a more effective
      management and offer a better prognosis.

PMID- 28495484
TI  - Insights on Heme Synthesis in the Malaria Parasite.
AB  - The malaria parasite has a functional heme-biosynthetic pathway, although it can
      access host hemoglobin-heme. The heme pathway is dispensable for blood stages,
      but essential in the mosquito stages which do not acquire hemoglobin-heme. We
      propose that the blood stage parasites maintain a dynamic heme pool through
      multiple back-up mechanisms.

PMID- 28495485
TI  - Mosquito Biting Modulates Skin Response to Virus Infection.
AB  - Mosquito-borne infections are increasing in number and are spreading to new
      regions at an unprecedented rate. In particular, mosquito-transmitted viruses,
      such as those that cause Zika, dengue, West Nile encephalitis, and chikungunya,
      have become endemic or have caused dramatic epidemics in many parts of the world.
      Aedes and Culex mosquitoes are the main culprits, spreading infection when they
      bite. Importantly, mosquitoes do not act as simple conduits that passively
      transfer virus from one individual to another. Instead, host responses to
      mosquito-derived factors have an important influence on infection and disease,
      aiding replication and dissemination within the host. Here, we discuss the latest
      research developments regarding this fascinating interplay between mosquito,
      virus, and the mammalian host.

PMID- 28495486
TI  - March 2017 (vol. 216, no. 3, page 250).

PMID- 28495487
TI  - Effect of Psychiatric Illness on Acute Care Utilization at End of Life From
      Serious Medical Illness.
AB  - CONTEXT: Little is known about psychiatric illness and utilization of end-of-life
      care. OBJECTIVES: We hypothesized that preexisting psychiatric illness would
      increase hospital utilization at end of life among patients with chronic medical
      illness due to increased severity of illness and care fragmentation. METHODS: We
      reviewed electronic health records to identify decedents with one or more of
      eight chronic medical conditions based on International Classification of
      Diseases-9 codes. We used International Classification of Diseases-9 codes and
      prescription information to identify preexisting psychiatric illness. Regression
      models compared hospital utilization among patients with and without psychiatric
      illness. Path analyses examined the effect of severity of illness and care
      fragmentation. RESULTS: Eleven percent of 16,214 patients with medical illness
      had preexisting psychiatric illness, which was associated with increased risk of
      death in nursing homes (P = 0.002) and decreased risk of death in hospitals (P <
      0.001). In the last 30 days of life, psychiatric illness was associated with
      reduced inpatient and intensive care unit utilization but increased emergency
      department utilization. Path analyses confirmed an association between
      psychiatric illness and increased hospital utilization mediated by severity of
      illness and care fragmentation, but a stronger direct effect of psychiatric
      illness decreasing hospitalizations. CONCLUSION: Our findings differ from the
      increased hospital utilization for patients with psychiatric illness in
      circumstances other than end-of-life care. Path analyses confirmed hypothesized
      associations between psychiatric illness and increased utilization mediated by
      severity of illness and care fragmentation but identified more powerful direct
      effects decreasing hospital use. Further investigation should examine whether
      this effect represents a disparity in access to preferred care.

PMID- 28495488
TI  - Vascular Age, RR, ALLY, RALLY and Vascular Speed, Based on SCORE: Relations
      Between New Concepts of Cardiovascular Prevention.

PMID- 28495489
TI  - Optical Coherence Tomography Findings in Patients With Stent Thrombosis.
AB  - INTRODUCTION AND OBJECTIVES: Stent thrombosis (ST) is a rare but potentially
      serious complication. Optical coherence tomography (OCT) provides high-resolution
      images and additional information to angiography in the study of this event.
      METHODS: Prospective study of patients with ST undergoing reintervention with OCT
      imaging. RESULTS: The study included a total of 40 consecutive patients with ST.
      Mean age was 69 +/- 13 years and 83% were male. Early ST (<= 30 days) was
      observed in 16 patients and late ST (> 30 days) in 24 patients. Stent thrombosis
      occurred in 17 bare-metal stents and 23 drug-eluting stents. In 34 patients
      (85%), adequate OCT images were obtained at the time of the ST. The predominant
      mechanism in early ST was stent malapposition (39%). In late ST, high frequencies
      of uncovered (46%) and malapposed struts (17%) were observed, especially in
      patients with drug-eluting stents. Furthermore, the presence of
      neoatherosclerosis was very high (67%) in patients with late ST. After
      intervention, improvements were observed in malapposition length and the amount
      of residual thrombus. CONCLUSIONS: OCT allows identification of the underlying
      mechanisms potentially involved in ST. This imaging modality is helpful in
      guiding reintervention in these patients, which improves the area and length of
      malapposition, as well as the maximal residual thrombus area.

PMID- 28495490
TI  - Further evidence for the association between LRP8 and schizophrenia.
AB  - Previous studies (including genome-wide association study (GWAS) and candidate
      gene studies) have revealed the important roles of genetic risk factors in
      schizophrenia, and RELN has been identified as a risk gene for this illness. We
      recently found that the low-density lipoprotein receptor-related protein 8
      (LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly
      associated with schizophrenia and bipolar disorder in European populations. To
      further enhance our understanding of its role in the risk of psychiatric
      illnesses, we conducted meta-analyses of a higher density of single nucleotide
      polymorphisms (SNPs, N=173) in LRP8 to understand their associations with
      schizophrenia in much larger samples (39,400 cases and 50,357 controls) from
      populations of European, Chinese and African American ancestries. The significant
      risk SNPs then underwent further analyses to understand their correlations with
      bipolar disorder and anxiety disorders, as well as LRP8 expression. We observed
      that rs5177 in the 3' untranslated region (3'UTR) of LRP8 was associated with
      schizophrenia and other psychiatric disorders, and rs5177 was also associated
      with LRP8 mRNA expression. These data further support LRP8 as a schizophrenia
      susceptibility gene, and suggest that this variant is likely a risk locus in
      general populations.

PMID- 28495491
TI  - A computational algorithm for personalized medicine in schizophrenia.
AB  - Despite advances in sequencing candidate genes and whole genomes, no method has
      accurately predicted who will or will not benefit from a specific antipsychotic
      medication among patients with schizophrenia. We propose a computational
      algorithm that utilizes a person-centered approach that directly identifies
      individual patients who will respond to a specific antipsychotic medication. The
      algorithm was applied to the data obtained from the Clinical Antipsychotic Trials
      of Intervention Effectiveness (CATIE) study. The predictors were either (1) 13
      single-nucleotide polymorphisms (SNPs) and 53 baseline variables or (2) 25 SNPs
      and the same 53 baseline variables, depending on the existing findings and data
      availability. The outcome variables were either (1) improvement in the Positive
      and Negative Syndrome Scale (PANSS) (Yes/No) or (2) completion of phase 1/1A
      (Yes/No). Each of those four predictor-outcome combinations was tried for each of
      the five antipsychotic medications (Perphenazine, Olanzapine, Quetiapine,
      Risperidone, and Ziprasidone), leading to 20 prediction experiments. For 18 out
      of 20 experiments, all three performance measures were greater than 0.50
      (sensitivity 0.51-0.79, specificity 0.52-0.79, accuracy 0.52-0.74). Notably, the
      model provided a promising prediction for Ziprasidone for the case involving
      completion of phase 1/1A (Yes/No) predicted by 13 SNPs and 53 baseline variables
      (sensitivity 0.75, specificity 0.74, accuracy 0.74). The proposed algorithm
      simultaneously used both genetic information and clinical profiles to predict
      individual patients' response to antipsychotic medications. As the method is not
      disease-specific but a general algorithm, it can be easily adopted in many other
      clinical practices for personalized medicine.

PMID- 28495492
TI  - The complex relationship between self-reported 'personal recovery' and clinical
      recovery in schizophrenia.
AB  - Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR
      and CR, respectively) reflect different perspectives in schizophrenia outcome,
      not necessarily concordant with each other and usually representing the
      consumer's or the therapist's point of view. By means of a cluster analysis on
      SRPR-related variables, we identified three clusters. The first and third cluster
      included subjects with the best and the poorest clinical outcome respectively.
      The second cluster was characterized by better insight, higher levels of
      depression and stigma, lowest self-esteem and personal strength, and highest
      emotional coping. The first cluster showed positive features of recovery, while
      the third cluster showed negative features. The second cluster, with the most
      positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture
      of positive and negative personal and clinical features of recovery. The present
      results suggest the need for a characterization of persons with schizophrenia
      along SRPR and CR dimensions to design individualized and integrated treatment
      programs aimed to improve insight and coping strategies, reduce stigma, and shape
      recovery styles.

PMID- 28495494
TI  - Unlimited niche packing in a Lotka-Volterra competition game.
AB  - A central question in the study of ecology and evolution is: "Why are there so
      many species?" It has been shown that certain forms of the Lotka-Volterra (L-V)
      competition equations lead to an unlimited number of species. Furthermore, these
      authors note how any change in the nature of competition (the competition kernel)
      leads to a finite or small number of coexisting species. Here we build upon these
      works by further investigating the L-V model of unlimited niche packing as a
      reference model and evolutionary game for understanding the environmental factors
      restricting biodiversity. We also examine the combined eco-evolutionary dynamics
      leading up to the species diversity and traits of the ESS community in both
      unlimited and finite niche-packing versions of the model. As an L-V game with
      symmetric competition, we let the strategies of individuals determine the
      strength of the competitive interaction (like competes most with like) and also
      the carrying capacity of the population. We use a mixture of analytic proofs (for
      one and two species systems) and numerical simulations. For the model of
      unlimited niche packing, we show that a finite number of species will evolve to
      specific convergent stable minima of the adaptive landscape (also known as
      species archetypes). Starting with a single species, faunal buildup can proceed
      either through species doubling as each diversity-specific set of minima are
      reached, or through the addition of species one-by-one by randomly assigning a
      speciation event to one of the species. Either way it is possible for an
      unlimited number or species to evolve and coexist. We examine two simple and
      biologically likely ways for breaking the unlimited niche-packing: (1) some
      minimum level of competition among species, and (2) constrain the fundamental
      niche of the trait space to a finite interval. When examined under both
      ecological and evolutionary dynamics, both modifications result in convergent
      stable ESSs with a finite number of species. When the number of species is held
      below the number of species in an ESS coalition, we see a diverse array of
      convergent stable niche archetypes that consist of some species at maxima and
      some at minima of the adaptive landscape. Our results support those of others and
      suggest that instead of focusing on why there are so many species we might just
      as usefully ask, why are there so few species?

PMID- 28495493
TI  - The value of novelty in schizophrenia.
AB  - Influential models of schizophrenia suggest that patients experience incoming
      stimuli as excessively novel and motivating, with important consequences for
      hallucinatory experience and delusional belief. However, whether schizophrenia
      patients exhibit excessive novelty value and whether this interferes with
      adaptive behaviour has not yet been formally tested. Here, we employed a three
      armed bandit task to investigate this hypothesis. Schizophrenia patients and
      healthy controls were first familiarised with a group of images and then asked to
      repeatedly choose between familiar and unfamiliar images associated with
      different monetary reward probabilities. By fitting a reinforcement-learning
      model we were able to estimate the values attributed to familiar and unfamiliar
      images when first presented in the context of the decision-making task. In line
      with our hypothesis, we found increased preference for newly introduced images
      (irrespective of whether these were familiar or unfamiliar) in patients compared
      to healthy controls and this to correlate with severity of hallucinatory
      experience. In addition, we found a correlation between value assigned to novel
      images and task performance, suggesting that excessive novelty value may
      interfere with optimal learning in patients, putatively through the disruption of
      the mechanisms regulating exploration versus exploitation. Our results suggest
      excessive novelty value in patients, whereby even previously seen stimuli acquire
      higher value as the result of their exposure in a novel context - a form of
      'hyper novelty' which may explain why patients are often attracted by familiar
      stimuli experienced as new.

PMID- 28495496
TI  - Aggressive digital papillary adenocarcinoma: A clinicopathological study of 19
      cases.
AB  - BACKGROUND: Aggressive digital papillary adenocarcinomas (ADPA) are malignant
      tumors of sweat glands having recurrence/metastatic potential. OBJECTIVE: We
      sought to describe the clinical/histopathological characteristics of a series of
      ADPA. METHODS: This is a retrospective case series of 19 ADPA. RESULTS: The
      tumors occurred in 17 men and 2 women (mean age: 47 years). They involved digits
      (15), big toe (3), and palm (1), and measured from 3 to 30 mm. They were mostly
      solid and cystic, with papillary projections and tubular structures. Atypia was
      mostly mild to moderate. Tumors tested positive for p63, keratin 7, keratin 77
      (eccrine duct-specific), PHLDA1, and epithelial membrane antigen in most cases,
      and for carcinoembryonic antigen, smooth muscle actin, S100 protein, estrogen,
      progesterone, and androgen receptors in 50%. Mean Ki67 proliferation index was
      15%. Local recurrence was observed in 4 cases. One patient had axillary lymph
      node metastasis. Histopathologic parameters were not predictive of evolution.
      Conservative surgical treatment, performed in 7 of 19 cases, did not result in
      more recurrences than amputation. LIMITATIONS: The study was retrospective and
      the number of cases is small. CONCLUSION: ADPA are histologically variable, but
      papillary projections are always present. Keratin 77 expression suggests an
      eccrine origin. P63 is helpful to exclude metastasis. Conservative surgery may be
      sufficient in some cases.

PMID- 28495498
TI  - Venous thromboembolism in patients with pemphigus: A cohort study.
AB  - BACKGROUND: Venous thromboembolism (VTE) has been reported to be a significant
      cause of death in patients with pemphigus. OBJECTIVE: We sought to assess the
      incidence and characteristics of VTE in patients with pemphigus. METHODS: A
      retrospective study following a cohort of 172 patients with newly diagnosed
      pemphigus for the development of VTE was conducted. RESULTS: Over a mean follow
      up time of 4 years, 10 patients (6%) had development of VTE at a median of 4
      months from pemphigus diagnosis. The highest risk was found in the first year, at
      5 VTE events per 100 patient-years or a 5% VTE risk for that first year. Five
      patients had deep vein thromboses, 4 had pulmonary embolisms, and 1 had both. Age
      and gender were not related to the VTE risk. Most patients had VTE risk factors,
      either hereditary or acquired as the result of pemphigus treatments and their
      complications, including hospitalization, immobilization, and infections.
      LIMITATIONS: The use of existing health records limited the assessment of
      asymptomatic VTE and VTE risk factors; a matched control population was not
      studied. CONCLUSIONS: VTEs are not rare in patients with pemphigus, more so in
      the first year after diagnosis. VTE risk must be assessed in all patients,
      especially when hospitalized, and thrombo-prophylaxis should be initiated in
      qualifying cases.

PMID- 28495495
TI  - Translating in vitro ligand bias into in vivo efficacy.
AB  - It is increasingly apparent that ligand structure influences both the efficiency
      with which G protein-coupled receptors (GPCRs) engage their downstream effectors
      and the manner in which they are activated. Thus, 'biased' agonists, synthetic
      ligands whose intrinsic efficacy differs from the native ligand, afford a
      strategy for manipulating GPCR signaling in ways that promote beneficial signals
      while blocking potentially deleterious ones. Still, there are significant
      challenges in relating in vitro ligand efficacy, which is typically measured in
      heterologous expression systems, to the biological response in vivo, where the
      ligand is acting on natively expressed receptors and in the presence of the
      endogenous ligand. This is particularly true of arrestin pathway-selective
      'biased' agonists. The type 1 parathyroid hormone receptor (PTH1R) is a case in
      point. Parathyroid hormone (PTH) is the principal physiological regulator of
      calcium homeostasis, and PTH1R expressed on cells of the osteoblast lineage are
      an established therapeutic target in osteoporosis. In vitro, PTH1R signaling is
      highly sensitive to ligand structure, and PTH analogs that affect the
      selectivity/kinetics of G protein coupling or that engage arrestin-dependent
      signaling mechanisms without activating heterotrimeric G proteins have been
      identified. In vivo, intermittent administration of conventional PTH analogs
      accelerates the rate of osteoblastic bone formation, largely through known cAMP
      dependent mechanisms. Paradoxically, both intermittent and continuous
      administration of an arrestin pathway-selective PTH analog, which in vivo would
      be expected to antagonize endogenous PTH1R-cAMP signaling, also increases bone
      mass. Transcriptomic analysis of tissue from treated animals suggests that
      conventional and arrestin pathway-selective PTH1R ligands act in largely
      different ways, with the latter principally affecting pathways involved in the
      regulation of cell cycle, survival, and migration/cytoskeletal dynamics. Such
      multi-dimensional in vitro and in vivo analyses of ligand bias may provide
      insights into the physiological roles of non-canonical arrestin-mediated
      signaling pathways in vivo, and provide a conceptual framework for translating
      arrestin pathway-selective ligands into viable therapeutics.

PMID- 28495497
TI  - Risk for hepatitis B and C virus reactivation in patients with psoriasis on
      biologic therapies: A retrospective cohort study and systematic review of the
      literature.
AB  - BACKGROUND: Patients with psoriasis on biologic therapies and a history of viral
      hepatitis carry a risk for reactivation. OBJECTIVE: We evaluated safety of
      biologic therapies in psoriasis patients seropositive for hepatitis B or C
      viruses (HBV, HCV). METHODS: A retrospective cohort study design was used.
      Clinical and laboratory data for 30 patients undergoing biologic therapy who were
      seropositive for HBV or HCV were evaluated. Next, a systematic review was
      performed. Primary outcomes were hepatitis and viral reactivation during therapy.
      Treatment duration and antiviral prophylaxis were also recorded. RESULTS:
      Serology indicated HCV infection in 4 patients, past HBV infection in 17
      patients, isolated core antibody in 8 patients, and chronic HBV infection in 1
      patient. During follow-up (mean 4.85 +/- 3.1 years), no patients experienced
      hepatitis or viral reactivation. The systematic review of the literature included
      49 studies comprising 312 patients followed for a mean of 30.9 months. Viral
      reactivation occurred in 2/175 patients who were seropositive for core antibody
      and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively)
      compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%).
      Three of these 8 patients with reactivated HBV infection received antiviral
      prophylaxis. LIMITATIONS: We pooled heterogeneous studies evaluating different
      biologic therapies. CONCLUSION: Biologic therapies pose minimal risk for viral
      reactivation in low-risk patients without hepatitis seropositive for HCV or HBV
      core antibody but are a considerable risk in patients with chronic HBV infection,
      highlighting the necessity of antiviral prophylaxis.

PMID- 28495499
TI  - Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful
      in-field locoregional control: A review and analysis of the literature.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon radiosensitive,
      neuroendocrine malignancy. Treatment often involves surgery; however, older,
      sicker patients may not be candidates for an operation. Institutions have
      published data favoring the role of definitive radiotherapy for macroscopic
      locoregional disease. OBJECTIVE: Our objective was to report the outcome of
      patients treated with definitive radiotherapy. METHODS: We performed a systematic
      review of Medline, PubMed, and Embase databases for reported cases or series of
      definitive radiotherapy for macroscopic locoregional MCC. RESULTS: The mean
      radiation dose did not significantly differ between primary and regional sites
      (48.7 +/- 13.2 vs 49.4 +/- 10.1 Gy, P = .74). The rate of recurrence was
      calculated on the basis of the site of disease (11.7%) and per patient (14.3%).
      Recurrence was significantly more likely to occur at regional than at primary
      irradiated sites (16.3% vs 7.6%, P = .02). There was no association between
      radiotherapy dose and incidence of recurrence or nonrecurrence; primary (42.7 +/-
      23 vs 49.3 +/- 11.8 Gy, P = .197) and regional (48.6 +/- 10 vs 49.5 +/- 10.3 Gy,
      P = .77). LIMITATIONS: A limitation of this report is that most publications were
      retrospective; heterogeneity was present in the size of MCC and in radiotherapy
      details. CONCLUSIONS: Definitive radiotherapy for locoregional macroscopic MCC
      was found to confer clinically meaningful local and regional in-field control.

PMID- 28495500
TI  - Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.
AB  - Emulsion technology has been utilized extensively in the pharmaceutical industry.
      This article presents a comprehensive review of the literature on an important
      subcategory of emulsions, microemulsions. Microemulsions are optically
      transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that
      form spontaneously upon mixing of oil, water and emulsifier. This review is the
      first to address advantages and disadvantages, as well as considerations and
      challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016,
      431 publications related to microemulsion drug delivery were identified and
      screened according to microemulsion, drug classification, and surfactant types.
      Results indicate the use of microemulsions predominantly in lipophilic drug
      delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%)
      for oral or topical administration. Cancer is the disease state most targeted
      followed by inflammatory diseases, microbial infections and cardiovascular
      disease. Key generalizations from this analysis include: 1) microemulsion
      formulation is largely based on trial-and-error despite over 1200 publications
      related to microemulsion drug delivery since their discovery in 1943; 2)
      characterization using methods including interfacial tension, droplet size,
      electrical conductivity, turbidity and viscosity may provide additional
      information for greater predictability; 3) microemulsion drug delivery
      publications arise primarily from China (27%) and India (21%) suggesting
      additional research opportunities elsewhere.

PMID- 28495501
TI  - Semen modulated secretory activity of oviductal epithelial cells is linked to
      cellular proteostasis network remodeling: Proteomic insights into the early phase
      of interaction in the oviduct in vivo.
AB  - : The oviductal epithelium is crucial for the integrity of the female organ.
      Previously we got evidence that the surface proteome of oviductal epithelial
      cells (Oecs) is promptly altered in response to insemination and thus suggested
      that this early phase plays a notable regulatory role in maintaining cellular
      function. This study further aimed to assess the effect of semen on the cellular
      and molecular mechanisms in rabbit Oecs. A quantitative gel-based proteomic
      approach was applied to analyze changes at three time points (0h, 1h, 2h) after
      intrauterine insemination (IUI) compared to time matched controls. Within two
      hours the abundance of 22 protein species was evidently altered in the
      intracellular fraction. Functional analysis revealed that the proteins were
      primarily involved in proteostasis as well as metabolic processes. The analysis
      of phosphoproteins specified a role of mitogen-activated protein kinase (MAPK)
      signaling molecules. Concurrently, semen increased oviduct-specific glycoprotein
      (OVGP1) secretion. A correlation between OVGP1 abundance and microtubule
      associated proteins 1A/1B-light chain 3 lipidation was observed. The localization
      and changes in abundance of selected proteins were corroborated by antibody-based
      methods. These results clearly show that the early phase of interaction acts as a
      trigger for cellular adaptation to meet an altered demand in the female organ.
      SIGNIFICANCE: The oviductal epithelium and its secreted proteins exert a pivotal
      role in reproductive processes, including the final maturation of male gametes.
      Thereby, the regulation and subsequently the functionality of the oviductal
      epithelial cell layer are important factors for the establishment of the
      appropriate milieu in the female reproductive tract. Notably, male gametes
      themselves have been shown to be an extrinsic modulatory factor of the oviductal
      epithelium. Accordingly a comprehensive knowledge about the underlying cellular
      and molecular mechanisms in the epithelial cells is of interest, also with regard
      to in vitro purposes. So far, the role of the early phase of interaction in the
      female organ has not been considered in detail. To get a further insight into the
      underlying cellular and molecular mechanisms, herein we analyzed the effect of
      semen on oviductal epithelial cells (Oecs) on the intracellular proteome level
      within the first two hours after insemination. The present study revealed a
      directed response of Oecs in vivo and disclosed intracellular pathways that are
      affected by the interplay between semen and the female reproductive tract. The
      prompt adaptation of the secretory activity and remodeling of the oviductal
      epithelium was accompanied by the concerted alterations of protein species that
      are primarily involved in the maintenance of cellular homeostasis. Besides
      emphasizing the importance of the early interaction phase for subsequent
      reproductive processes, the gained knowledge might further be implemented for in
      vitro applications as well.

PMID- 28495502
TI  - Multipronged quantitative proteomics reveals serum proteome alterations in breast
      cancer intrinsic subtypes.
AB  - : Being molecularly heterogeneous, breast cancer tends to be a complicated
      oncological disease with high incidence rates throughout the world. The primary
      aim of this study was to identify the set of serum proteins with discriminatory
      capabilities towards the four major subtypes of breast cancer. We employed
      multipronged quantitative proteomic approaches like 2D-DIGE, iTRAQ and SWATH-MS
      and identified 307 differentially regulated proteins. Luminal A subtype consisted
      of 24, Luminal B subtype 38, HER2 Enriched subtype 17 and Triple negative breast
      cancer subtype 10 differentially regulated subtype specific proteins. These
      specific proteins were further subjected to bioinformatic tools which revealed
      the involvement in platelet degranulation, fibrinolysis, lipid metabolism, immune
      response, complement activation, blood coagulation, glycolysis and cancer
      signaling pathways in the subtypes of the breast cancer. The significant
      discrimination efficiency of the models generated through multivariate
      statistical analysis was decent to distinguish each of the four subtypes from
      controls. Further, some of the statistically significant differentially regulated
      proteins were verified and validated by immunoblotting and mass spectrometry
      based selected reaction monitoring (SRM) approach. Our Multipronged proteomics
      approaches revealed panel of serum proteins specifically altered for individual
      subtypes of breast cancer. The mass spectrometry data are available via
      ProteomeXchange with identifier PXD006441. BIOLOGICAL SIGNIFICANCE: Worldwide,
      breast cancer continues to be one of the leading causes of cancer related deaths
      in women and it encompasses four major molecular subtypes. As breast cancer
      treatment majorly depends on identification of specific subtype, it is important
      to diagnosis the disease at subtype level. Our results using multipronged
      quantitative proteomics identified 307 differentially regulated proteins in which
      24 were specific for Luminal A, 38 for Luminal B, 17 for HER2 enriched and 10
      proteins were specific for TN subtype. Bioinformatic analysis of these proteins
      revealed certain biological processes and pathways altered at subtype level and
      validation experiments of some of these proteins using immunoblotting and SRM
      assays are consistent with discovery data. This is the first comprehensive
      proteomic study on serum proteome alterations at subtype level which will not
      only help to distinguish subtype of breast cancer but also contribute to a better
      understanding of the molecular characteristic of breast cancer at individual
      subtype level.

PMID- 28495503
TI  - Sex-differences in the prevalence of Helicobacter pylori infection in pediatric
      and adult populations: Systematic review and meta-analysis of 244 studies.
AB  - BACKGROUND: The main outcome of Helicobacter pylori infection, i.e. gastric
      cancer, is more frequent in men, but there is no comprehensive synthesis of the
      evidence on a potential role of sex in the acquisition and/or persistence of
      infection. AIMS: To quantify the association between sex and H. pylori infection
      in pediatric and adult populations, through systematic review and meta-analysis.
      METHODS: PubMed(r) was searched, from inception to September 2015, to identify
      population-based studies reporting the prevalence and/or incidence of H. pylori
      infection in both sexes. Odds ratios (OR) or data to compute them were extracted;
      adjusted estimates were preferred, whenever available. The DerSimonian and Laird
      method was used to compute summary estimates and respective 95% confidence
      intervals (95%CI), separately for children and adults. RESULTS: Among a total of
      244 studies, mostly cross-sectional, male sex was associated with a greater
      prevalence of H. pylori infection, both in children (102 studies, OR=1.06, 95%CI:
      1.01, 1.12, I2=43.7%) and adults (169 studies, OR=1.12, 95%CI: 1.09, 1.15,
      I2=68.5%). An underrepresentation of studies showing a negative association
      between male sex and infection was observed (Egger's test: p=0.006). CONCLUSIONS:
      Although further research is needed to understand the mechanisms by which sex may
      influence the acquisition and/or persistence of infection, our results support a
      small contribution of sex differences in the prevalence of infection to the male
      predominance of H. pylori-related outcomes, including gastric cancer.

PMID- 28495504
TI  - Renal Arterial Mycotic Aneurysm After Kidney Transplantation.
AB  - Mycotic aneurysm is a rare condition mostly attributable to Candida or
      Aspergillus species. About 20 cases of Candida-related arteritis have been
      reported in kidney transplant patients. Herein, we report the case of a 40-year
      old man who received a kidney from a deceased donor in whom an accidental
      digestive wound was made during organ retrieval. He presented with sudden anuria
      47 days after renal transplantation, revealing a large mycotic aneurysm of the
      kidney graft renal artery. Organs derived from donors in whom a digestive breach
      is noticed should be used with caution.

PMID- 28495505
TI  - Penile Fracture Following a Fall in a 7-Year-Old Male.
AB  - We report a rare case of isolated penile fracture in a prepubescent male caused
      by an accidental fall. The patient presented with swelling and ecchymosis on the
      base of the penis and along the penile shaft. A flexible cystoscopy was
      performed, which did not reveal any concomitant urethral injury. The penis was
      degloved and the corporal tear was closed with absorbable suture. Due to the
      location of the injury, ventral mobilization of the urethra was required. The
      pathophysiology of penile fracture as well as the diagnosis and management of
      this rare injury are discussed in this report.

PMID- 28495506
TI  - Use of Bipedicled Dorsal Penile Flap With Z Release Incision: A New Option in
      Redo Hypospadias Surgery.
AB  - OBJECTIVE: To solve the challenge in redo hypospadias surgery, we tried to use a
      bipedicled dorsal penile flap with a Z release incision in failed hypospadias
      cases and reported the outcome. MATERIALS AND METHODS: Thirty male children with
      3 or 4 previous unsuccessful hypospadias surgeries were included in our study.
      Our technique was done after at least 6 months from the last surgery. A flap of
      the dorsal penile skin was preserved and the skin lateral to the flap was
      dissected on each side. A small opening was done in the dartos proximal to flap.
      The glans was withdrawn through this opening with a ventral transposition of the
      flap. Z-plasty was used to compensate for the deficient dorsal skin; the Z-plasty
      had 3 limbs and all were made of equal length. RESULTS: The mean age of the
      patients was 5.4 +/- 1.8 years and the mean follow-up was 2.1 +/- 0.7 years. The
      technique was successful in 80%. Reoperation was required in 3 cases; all cases
      were managed using a 2-stage buccal mucosal graft. A small fistula at the coronal
      level developed in 2 cases but closed spontaneously within 1 month. All patients
      were voiding well and had a vertically oriented meatus at the tip of the glans
      and satisfactory cosmetic results. CONCLUSION: Repair of failed hypospadias using
      a bipedicled dorsal penile skin flap with Z release incision is a safe and simple
      procedure offering high success rates.

PMID- 28495507
TI  - Up and Away: Five Decades of Urologic Investigation in Microgravity.
AB  - A renewed global interest in manned space exploration has emerged, propelled by
      the challenge of reaching a new frontier: travel to the Red Planet, Mars. As the
      physiological changes induced by microgravity bear direct relevance to the safety
      and viability of these goals, we provide a historical narrative of the urologic
      investigations in space. We review the significant contributions to the
      understanding of the urologic consequences associated with exposure to
      microgravity, considerations for prolonged missions, and forward-looking efforts
      to manage emergent conditions remotely. Historical insights gleaned are poised to
      inform interplanetary travel, where urologic pathology will remain an important
      practical consideration.

PMID- 28495508
TI  - The effect of ALA-PDT under normoxia and cobalt chloride (CoCl2)-induced hypoxia
      on adhesion molecules (ICAM-1, VCAM-1) secretion by colorectal cancer cells.
AB  - BACKGROUND: The most fundamental problem in cancer biology research is to
      understand the mechanisms of cancer cell resistance to oncological therapies.
      Literature reports emphasize the important role of adhesion molecules:
      intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (ICAM-1
      and VCAM-1) in cancer progression and resistance to treatment. Photodynamic
      therapy (PDT) could become the component of a personalized approach to colorectal
      cancer, therefore we examined the effects of ALA (delta-aminolevulinic) acid PDT
      in normoxia and under cobalt chloride (CoCl2)-induced hypoxia on ICAM-1 and VCAM
      1 secretion by colorectal cancer cells. METHODS: Human colorectal cancer cells of
      different malignant potential SW480 and SW620 were used in the experiment. Cell
      lines were treated ALA, in order to achieve conditions comparable to in vivo
      hypoxia, CoCl2 was added, then cells were irradiated both in normoxia and in
      hypoxia-like conditions. Cell viability was assessed using the LDH and MTT assays
      and apoptosis. ICAM-1 and VCAM-1 concentrations were determined with the Bio -
      Plex ProTM Assay and System. RESULTS: The experiment revealed that ALA PDT under
      normoxia and CoCl2-induced hypoxia had no significant effect on ICAM-1 and VCAM-1
      dependent adhesion of colorectal cancer cells. The secretion of ICAM-1 by SW480
      ell line was more pronounced compared to ICAM-1 secretion by SW620 cells.
      CONCLUSION: Determination of tumor marker levels and especially adhesion
      molecules involved in metastatic spread is necessary. Our experiment reveals,
      that ALA PDT in normoxia and CoCl2-induced hypoxia has no effect on adhesion
      molecules secretion by colon cancer cells in vitro.

PMID- 28495509
TI  - Cloning of three heat shock protein genes (HSP70, HSP90alpha and HSP90beta) and
      their expressions in response to thermal stress in loach (Misgurnus
      anguillicaudatus) fed with different levels of vitamin C.
AB  - Heat shock protein 70 (HSP70) and 90 (HSP90) are the most broadly studied
      proteins in HSP families. They play key roles in cells as molecular chaperones,
      in response to stress conditions such as thermal stress. In this study, full
      length cDNA sequences of HSP70, HSP90alpha and HSP90beta from loach Misgurnus
      anguillicaudatus were cloned. The full-length cDNA of HSP70 in loach was 2332bp
      encoding 644 amino acids, while HSP90alpha and HSP90beta were 2586bp and 2678bp
      in length, encoding 729 and 727 amino acids, respectively. The deduced amino acid
      sequences of HSP70 in loach shared the highest identity with those of Megalobrama
      amblycephala and Cyprinus carpio. The deduced amino acid sequences of HSP90alpha
      and HSP90beta in loach both shared the highest identity with those of M.
      amblycephala. Their mRNA tissue expression results showed that the maximum
      expressions of HSP70, HSP90alpha and HSP90beta were respectively present in the
      intestine, brain and kidney of loach. Quantitative real-time PCR was employed to
      analyze the temporal expressions of HSP70, HSP90alpha and HSP90beta in livers of
      loaches fed with different levels of vitamin C under thermal stress. Expression
      levels of the three HSP genes in loach fed the diet without vitamin C
      supplemented at 0 h of thermal stress were significantly lower than those at 2 h,
      6 h, 12 h and 24 h of thermal stress. It indicated that expressions of the three
      HSP genes were sensitive to thermal stress in loach. The three HSP genes in
      loaches fed with 1000 mg/kg vitamin C expressed significantly lower than other
      vitamin C groups at many time points of thermal stress, suggesting 1000 mg/kg
      dietary vitamin C might decrease the body damages caused by the thermal stress.
      This study will be of value for further studies into thermal stress tolerance in
      loach.

PMID- 28495510
TI  - In vitro characterization of grass carp (Ctenopharyngodon idella) IL-26 in
      regulating inflammatory factors.
AB  - Interleukin 26 (IL-26) gene has been identified in human, amphibian and teleost
      but not in rodents. It is well accepted that IL-26 was a crucial member of IL-10
      family which acts as a pro-inflammatory cytokine in human. However, the role of
      IL-26 in regulating inflammation in lower vertebrates including teleost has not
      been defined yet. In the present study, grass carp IL-26 (gcIL-26) coding
      sequence was isolated and identified. Its chromosomal synteny was also analyzed,
      showing that gcIL-26 gene is flanked by IL-22 and IFN-gamma genes with the same
      transcriptional orientation as seen in human, amphibian and zebrafish. Given that
      zebrafish and grass carp IL-26 shared relatively low amino acid identities with
      human IL-26, the functional roles of fish IL-26 are indispensable to be
      elucidated. Accordingly, recombinant gcIL-26 (rgcIL-26) was prepared by using
      Pichia pastoris expression system, and it was found to be partially glycosylated.
      Using grass carp head kidney leucocytes as cell model, rgcIL-26 displayed the
      bioactivity to stimulate the mRNA expression of some pro-inflammatory cytokines
      including IL-8, IL-1beta and IL-6, while inhibit mRNA expression of an anti
      inflammatory cytokine, IL-10. Moreover, rgcIL-26 also up-regulated inos
      expression and NO production in grass carp monocytes/macrophages, strengthening
      its pro-inflammatory properties in fish. Those results collectively demonstrated
      the functional role of IL-26 in regulating inflammatory response in fish.

PMID- 28495511
TI  - Biomolecular NMR: Past and future.
AB  - The editors of this special volume suggested this topic, presumably because of
      the perspective lent by our combined >90-year association with biomolecular NMR.
      What follows is our personal experience with the evolution of the field, which we
      hope will illustrate the trajectory of change over the years. As for the future,
      one can confidently predict that it will involve unexpected advances. Our
      narrative is colored by our experience in using the NMR Facility for Biomedical
      Studies at Carnegie-Mellon University (Pittsburgh) and in developing similar
      facilities at Purdue (1977-1984) and the University of Wisconsin-Madison (1984-).
      We have enjoyed developing NMR technology and making it available to
      collaborators and users of these facilities. Our group's association with the
      Biological Magnetic Resonance data Bank (BMRB) and with the Worldwide Protein
      Data Bank (wwPDB) has also been rewarding. Of course, many groups contributed to
      the early growth and development of biomolecular NMR, and our brief personal
      account certainly omits many important milestones.

PMID- 28495512
TI  - Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin.
AB  - Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer,
      while chemoresistance remains a challenge. Recent evidence highlights the crucial
      regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the
      roles and regulatory mechanisms of the novel lncRNA, cancer susceptibility
      candidate 2 (CASC2), in cervical cancer tumorigenesis and chemoresistance are
      poorly understood. In this study, CASC2 expression was down-regulated in cervical
      cancer tissues, and was related to a shorter survival time and poorer
      clinicopathologic features. Exogenous CACS2 alone was sufficient to inhibit
      cervical cancer cell proliferation and amplified DDP-induced repression of cell
      proliferation. A lower expression of CACS2 was observed in the DDP-resistant
      cervical cancer tissues, compared to DDP-sensitive cancer tissues; CACS2
      overexpression could sensitize DDP-resistant cervical cancer cell (HeLa/DDP and
      CaSki/DDP) to DDP. Further functional experiments indicate that CASC2 upregulated
      PTEN expression by direct inhibiting miR-21 in the DDP-resistant cancer cells,
      leading to the down-regulation of p-AKT protein. In DDP-resistant cervical cancer
      tissues, miR-21 was up-regulated while PTEN was down-regulated. Taken together,
      these observations suggest CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays
      an important role in cervical cancer sensitivity to DDP and may serve as a
      potential target for cancer diagnosis and treatment.

PMID- 28495513
TI  - High hydrostatic pressure affects antigenic pool in tumor cells: Implication for
      dendritic cell-based cancer immunotherapy.
AB  - High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based
      active immunotherapy for prostate, lung and ovarian cancer. We showed here that
      HHP treatment of selected human cancer cell lines leads to a degradation of tumor
      antigens which depends on the magnitude of HHP applied and on the cancer cell
      line origin. Whereas prostate or ovarian cell lines displayed little protein
      antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are
      hardly detected in lung cancer cell line after treatment with HHP 250MPa at the
      same time. On the other hand, quick reduction of tumor antigen-coding mRNA was
      observed at HHP 200MPa immediately after treatment in all cell lines tested. To
      optimize the DC-based active cellular therapy protocol for HHP-sensitive cell
      lines the immunogenicity of HHP-treated lung cancer cells at 150, 200 and 250MPa
      was compared. Lung cancer cells treated with HHP 150MPa display characteristics
      of immunogenic cell death, however cells are not efficiently phagocytosed by DC.
      Despite induction of the highest number of antigen-specific CD8+ T cells, 150 MPa
      treated lung cancer cells survive in high numbers. This excludes their use in DC
      vaccine manufacturing. HHP of 200MPa treatment of lung cancer cells ensures the
      optimal ratio of efficient immunogenic killing and delivery of protein antigens
      in DC. These results represent an important pre-clinical data for generation of
      immunogenic killed lung cancer cells in ongoing NSCLC Phase I/II clinical trial
      using DC-based active cellular immunotherapy (DCVAC/LuCa).

PMID- 28495514
TI  - Neurobehavioral risks of SSRIs in pregnancy: Comparing human and animal data.
AB  - During the last twenty years, in spite of extensive literature regarding the use
      of SSRIs in pregnancy, confusion still exists as to possible long-term risks of
      these drugs on the offspring. Possible negative effects relate to
      neurodevelopmental outcome and association with Autism Spectrum Disorder (ASD).
      Most neurodevelopmental follow up studies did not find significant cognitive
      impairment except from some apparently transient, gross motor delay and slight
      impairment of language abilities. The literature on the possible association of
      SSRIs with ASD is inconsistent, and if an association exists it is apparently
      throughout pregnancy. There is a higher risk for psychiatric problems which might
      be related to the maternal psychiatric disease for which SSRIs were prescribed.
      Most animal studies did not demonstrate teratogenicity, and the observed
      neurodevelopmental problems are of models with depression induced during
      pregnancy. Depression seems to be associated with up regulation of hypothalamic
      pituitary adrenal (HPA) axis and prenatal SSRIs also seem to affect the HPA axis
      in animals and man, but the possible long-term outcome has yet to be established.
      SSRIs might apparently also induce epigenetic changes. There is, however, little
      proof for significant damaging effects of SSRIs in pregnancy. When evaluating the
      risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with
      treatment discontinuation e.g. higher frequency of relapse and postpartum
      depression appears to outweigh the potential risks of treatment. Moreover,
      maternal depression may negatively affect the child's development, emphasizing
      the importance of prevention by appropriate treatment during pregnancy with the
      least minimal effective dose.

PMID- 28495515
TI  - Renal protective effects of thymoquinone against sodium nitrite-induced chronic
      toxicity in rats: Impact on inflammation and apoptosis.
AB  - AIMS: Sodium nitrite is a widely used color fixative and preservative. However,
      it has been reported to exert deleterious toxic effects on various body organs.
      Moreover, thymoquinone (TQ), the active constituent of Nigella sativa oil is
      known to possess beneficial antioxidant and anti-inflammatory effects. The
      present study was conducted to evaluate the potential protective effects of TQ
      against sodium nitrite-induced renal toxicity. MAIN METHODS: Male Sprague-Dawley
      rats were treated with sodium nitrite (80mg/kg, po, daily) in presence or absence
      of TQ (25 and 50mg/kg, po, daily). Morphological changes in renal sections were
      assessed by staining with Hematoxylin/Eosin and Periodic acid-Schiff. Renal
      homogenate was used for measurement of oxidative stress markers (MDA and GSH),
      inflammatory markers (CRP, TNF-alpha, IL-6, IL-1beta), anti-inflammatory
      cytokines (IL-10 and IL-4) and apoptotic markers (caspase-3/caspase-8/caspase-9).
      KEY FINDINGS: Treatment with sodium nitrite significantly increased markers of
      renal dysfunction, oxidative stress, inflammation and apoptosis. These effects
      were markedly attenuated by TQ in dose dependent manner. SIGNIFICANCE: TQ has a
      potential protective effect against sodium nitrite-induced renal toxicity. This
      can be attributed to its ability to dampen oxidative stress, restore the normal
      balance between pro- and anti-inflammatory cytokines and protect renal tissue
      form extrinsic and intrinsic apoptosis.

PMID- 28495516
TI  - 7-O-geranylquercetin-induced autophagy contributes to apoptosis via ROS
      generation in human non-small cell lung cancer cells.
AB  - AIMS: To investigate the antitumor effects of 7-O-geranylquercetin (GQ), a novel
      O-alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC)
      cell lines A549 and NCI-H1975 and the corresponding mechanisms. MAIN METHODS:
      Cell viability was assessed using MTT assay. The expression of proteins involved
      in apoptosis and autophagy was measured using western blotting. Besides,
      apoptosis was determined with DAPI staining, Annexin V-PI staining and
      transmission electron microscopy (TEM) assay, and autophagy was observed with TEM
      assay. Cell cycle and reactive oxygen species (ROS) level were detected using
      flow cytometry. KEY FINDINGS: GQ inhibited viability of A549 and NCI-H1975 cells
      in a dose- and time-dependent manner without apparent cytotoxicity to normal
      human lung fibroblast cells. GQ down-regulated the expression of apoptosis
      related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of
      cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell
      apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced
      autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of
      autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of
      p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively
      inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation
      of ROS, and ROS inhibitor N-acetylcysteine could reverse GQ-induced autophagy and
      apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS
      generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to
      apoptosis. SIGNIFICANCE: Our findings highlight that GQ is a promising anticancer
      agent for the treatment of lung cancer.

PMID- 28495517
TI  - Berberine confers neuroprotection in coping with focal cerebral ischemia by
      targeting inflammatory cytokines.
AB  - SCOPE: Existing research indicates that anti-inflammatory and antioxidant
      properties of berberine play major roles in coping with oxidative stress in
      neurodegenerative diseases, but it is not known if this isoquinoline alkaloid
      affects inflammatory cytokines such as interleukin 10 in focal cerebral ischemia.
      METHODS AND RESULTS: Male Wistar rats (10 weeks old) were treated with 40mg/kg
      concentration of berberine 1h after focal cerebral ischemia and the anti
      inflammatory properties of berberine were evaluated by immunohistochemical
      analysis, water content measure and behavioral tests. Evaluation of infarct
      volume was performed by TTC staining. Immunohistochemistry and behavioral
      assessment indicated recovery in treatment group compared to only ischemia group.
      The infarct volume decreased in treatment group compared to ischemia group.
      Berberine administration significantly decreased brain edema and contributed to
      the restoration of motor function. Moreover, berberine potently contributed to
      neuroprotection in motor area through downregulation of pro-inflammatory
      cytokines and upregulation of anti-inflammatory cytokines. CONCLUSIONS: These
      findings confirm the validity of berberine as a potent anti-inflammatory agent in
      treatment of ischemic stroke.

PMID- 28495518
TI  - Prenatal exposure to low-dose diclofenac sodium does not affect total neuron
      numbers in spinal segment T13 in rats.
AB  - The main purpose of the present study was to investigate the effects of
      diclofenac sodium (DS) on the total number of neurons in segment T13 of the
      spinal cord of offspring of pregnant rats using stereological methods. Eighteen
      adult female Wistar albino rats weighing 150-200g were used. Pregnant female rats
      were divided into three groups; a control group, a sham group and a DS (1mg/kg,
      intramuscular) exposed group. The DS and sham groups received injection from the
      5th day of gestation to the 19th. Twenty eight days after birth, the offspring
      rats were perfused with 4% buffered formalin. T13, which is one of transverse
      spinal cord segments, were isolated and processed for routine paraffin histology.
      5MUm sections were obtained using a rotary microtome according to systematic
      random sampling strategies. Every 40th section was taken and sections were
      stained with modified Giemsa. All types of motor neuron cell were identified
      according to their morphology. In this study, the "disector-Cavalieri
      combination" method was used in the stereological examination of neurons. The
      motor neurons were counted in the right gray matter of the ventral horn in the
      spinal cord segment. The Kruskal-Wallis test was used for comparison the groups.
      In terms of motoneuron number, no significant difference among the groups was
      found (p>0.05). In conclusion, our results indicated that prenatal exposure to DS
      has no effect on the total number of motor neuron of the offspring rats.

PMID- 28495519
TI  - The involvement of autophagy and cytoskeletal regulation in TDCIPP-induced SH
      SY5Y cell differentiation.
AB  - Exposure and toxicity to organophosphate-based flame retardants are an increasing
      health concern. Neurons appear to be particularly vulnerable to the effects of
      these chemicals. For example, in vitro studies have shown that tris(1,3-dichloro
      2-propyl) phosphate (TDCIPP) induces apoptosis and autophagy in neural cells. In
      the present study, we investigated the cell biological mechanisms of TDCIPP
      induced neurotoxicity using undifferentiated human SH-SY5Y neuroblastoma cells as
      a model. Interestingly, TDCIPP treatment promoted differentiation in SH-SY5Y
      cells, which displayed various alterations including neurite elongation, an
      expansion of the numbers of neurite-bearing cells, and an increase in expression
      of cytoskeletal components normally enriched in neurons. Furthermore, the
      upregulation of microtubule-associated protein light chain 3, the degradation of
      p62/sequestosome 1, and the formation of autophagosomes occurred in treated
      cells, suggesting that TDCIPP exposure induces autophagy. However, pretreatment
      with the autophagy inhibitor 3-methyladenine suppressed TDCIPP-induced autophagy
      and reduced expression of the aforementioned cytoskeletal components. This
      correlated with a reduction in neurite outgrowth and numbers of neurite-bearing
      cells. Taken together, these results indicate that autophagy might promote TDCIPP
      induced SH-SY5Y cell differentiation, which leads to an increase in expression of
      cytoskeletal components and neurite outgrowth. This study offers key insights
      into the mechanisms of neurotoxicity associated with this commonly used
      organophosphate.

PMID- 28495520
TI  - Brain uptake of deltamethrin in rats as a function of plasma protein binding and
      blood-brain barrier maturation.
AB  - Pyrethroids, including permethrin and deltamethrin (DLM), are very widely used of
      insecticides. It was hypothesized that lower plasma binding and increased blood
      brain barrier (BBB) penetration of DLM in immature rats contribute to the higher
      brain concentrations of DLM and more pronounced neurotoxicity reported in this
      age group. The left brain of anesthetized adult rats was perfused for 2min via a
      carotid artery with 1MUM 14C-DLM in: 2-5% human serum albumin (HSA); plasma from
      adult and 15- and 21-d-old rats; and plasma from human donors of: birth-1 week, 1
      4 weeks, 4 weeks-1 year, 1-3 years and adults. The fraction of DLM bound and
      brain uptake of DLM did not vary significantly with the HSA concentration nor
      with the age of rat or human plasma donors. One, 10 and 50MUM 14C-DLM were
      perfused into the left-brain of anesthetized adult, 15- and 21-d-old rats. DLM
      deposition in the brain was linear over this range of concentrations and
      inversely related to age. The results of this investigation indicate that
      increased BBB permeability in the youngest rats enhances brain deposition of the
      insecticide. Plasma protein binding of DLM in immature rats and humans is not
      sufficiently diminished to impact its brain uptake.

PMID- 28495521
TI  - Efficacy of local glucocorticoid after local anesthetic in low back pain with
      lumbosacral transitional vertebra: A randomized placebo-controlled double-blind
      trial.
AB  - OBJECTIVE: The primary objective of this study was to compare the efficacy of
      local injection of a local anesthetic with a glucocorticoid versus a local
      anesthetic with saline to treat low back pain due to lumbosacral transitional
      vertebras (LSTV) with a pseudoarticulation. METHODS: A randomized placebo
      controlled double-blind study was conducted in patients with unilateral low back
      pain ascribed clinically to LSTV. Patients were randomized to lidocaine plus
      saline (LS group) or lidocaine plus cortivazol (LC group) injected locally under
      computed tomography guidance. The primary outcome measure was the 24-hour mean
      visual analog scale (VAS) score for low back pain 4 weeks after the injection.
      RESULTS: Of 16 randomized patients, 15 were included in the analysis, 8 in the LS
      group and 7 in the LC group. The mean VAS pain score at week 4 was not
      significantly different between the two groups. In the two groups pooled, the
      mean VAS pain score decreased significantly from baseline to week 4, from 5.52+/
      0.99 to 3.86+/-2.55 (P<=0.05). The difference remained significant at week 12.
      Significant improvements occurred in the EIFEL disability index and items of the
      Dallas Pain Questionnaire. No adverse events were recorded. CONCLUSION: In
      patients with chronic low back pain consistent with a symptomatic LSTV type II or
      IV in the Castellvi classification, a local injection of lidocaine with or
      without cortivazol may provide sustained improvements in pain and function. The
      underlying mechanism is unclear.

PMID- 28495522
TI  - Spondyloarthritis: An expanding cast of cellular actors.

PMID- 28495523
TI  - Hyaluronic acid: Still useful in knee osteoarthritis?

PMID- 28495524
TI  - Granulomatosis with polyangiitis (Wegener granulomatosis): A proteinase-3 driven
      disease?
AB  - Granulomatosis with polyangiitis (GPA, Wegener granulomatosis) is a systemic
      autoimmune vasculitis that affects small arteries, arterioles, and capillaries,
      most notably in the kidneys and lungs. In this disease, proteinase-3 (PR3),
      produced by neutrophils, is targeted by antineutrophil cytoplasmic antibodies
      (ANCA). Recent work by our group has shown how PR3 impairs the resolution of
      inflammation and deregulates the immune system. Normally, the clearance of
      activated neutrophils triggers an anti-inflammatory, pro-resolution process. In
      patients with GPA, however, macrophages phagocytose apoptotic neutrophils then
      release massive amounts of pro-inflammatory mediators, notably interleukin-1,
      thereby generating a pro-inflammatory microenvironment conducive to autoimmunity.
      This deregulation of immune processes is accompanied with activation of
      plasmacytoid dendritic cells and with polarization of T-helper-2 (Th2), Th9, and
      Th17 cells. These recent data highlight the dual role of PR3, both auto-antigenic
      and auto-inflammatory, thus potentially opening up new therapeutic avenues.

PMID- 28495526
TI  - Multidrug-resistant Pseudomonas aeruginosa skin and soft-tissue infection
      successfully treated with ceftolozane/tazobactam.
AB  - Ceftolozane/tazobactam (C/T) is a novel beta-lactam/beta-lactamase inhibitor
      combination antibiotic approved by the US Food and Drug Administration for the
      treatment of complicated intra-abdominal and urinary tract infections due to Gram
      negative bacteria, particularly extended-spectrum beta-lactamase-producing
      Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa strains.
      Here we report a case of MDR P. aeruginosa skin and soft-tissue infection
      successfully treated with C/T.

PMID- 28495525
TI  - Latent tuberculosis infection: the final frontier of tuberculosis elimination in
      the USA.
AB  - Since 1989, the USA has been pursuing the goal of tuberculosis elimination. After
      substantial progress during the past two decades, the rate of tuberculosis cases
      in the USA each year has now levelled off and remains well above the elimination
      threshold. Both epidemiological data and modelling underline the necessity of
      addressing latent tuberculosis infection if further progress is to be made in
      eliminating the disease. In this Personal View we explore next steps towards
      elimination. Given the estimated prevalence of latent tuberculosis infection,
      compared with the limited testing and treatment that currently occur, a major new
      effort is required. This effort should consist of a surveillance system or
      registry to monitor progress, scale-up of targeted testing for latent
      tuberculosis infection in at-risk populations, scale-up of short-course treatment
      regimens, engagement of affected communities and medical providers who serve
      those communities, and increased public health staffing for implementation and
      oversight. Such an effort would benefit greatly from the development of new
      tools, such as tests that better indicate reactivation risk, and even shorter
      latent tuberculosis infection treatment regimens than currently exist.

PMID- 28495527
TI  - Facilitating State-Wide Collaboration around Family Planning Care in the Context
      of Zika.
AB  - INTRODUCTION: Family planning providers have an important role to play in the
      response to the public health challenge posed by Zika. In the United States,
      there are high rates of unintended pregnancy, especially in states most at risk
      for mosquito-borne transmission of the Zika virus. This paper describes efforts
      by eight of these states (Arizona, California, Florida, Georgia, Louisiana,
      Mississippi, South Carolina, and Texas) to build capacity for quality family
      planning care in the context of Zika. METHODS: Drawing on resources developed by
      the Office of Population Affairs, including a toolkit for family planning care in
      the context of Zika, agencies and stakeholders involved in the family planning
      delivery system in Southern states at risk for mosquito-borne transmission met
      over several months in the summer of 2016 to coordinate efforts to respond to the
      risk of Zika in their jurisdictions. RESULTS: Through proactive communication and
      collaboration, states took steps to integrate Zika-related family planning care,
      including screening for Zika risk and providing appropriate, client-centered
      counseling. Challenges faced by the states included not having family planning
      included as a component of their state's Zika response effort, limited funding
      for family planning activities, and the need for robust communication networks
      between multiple state and federal agencies. CONCLUSIONS: The efforts described
      in this paper can help other states to integrate family planning into their Zika
      response. This is relevant to all states; even when mosquito-borne transmission
      is not occurring or expected, all states experience travel-related and sexually
      transmitted Zika infections.

PMID- 28495528
TI  - Hepatic ischemia/reperfusion injury disrupts the homeostasis of kidney primary
      cilia via oxidative stress.
AB  - Acute kidney injury (AKI) is a major complication of hepatic surgeries. The
      primary cilium protrudes to the lumen of kidney tubules and plays an important
      role in renal functions. Disruption of primary cilia homeostasis is highly
      associated with human diseases including AKI. Here, we investigated whether
      transient hepatic ischemia induces length change and deciliation of kidney
      primary cilia, and if so, whether reactive oxygen species (ROS)/oxidative stress
      regulates those. HIR induced damages to the liver and kidney with increases in
      ROS/oxidative stress. HIR shortened the cilia of kidney epithelial cells and
      caused them to shed into the urine. This shortening and shedding of cilia was
      prevented by Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, an
      antioxidant). The urine of patient undergone liver resection contained ciliary
      proteins. These findings indicate that HIR induces shortening and deciliation of
      kidney primary cilia into the urine via ROS/oxidative stress, suggesting that
      primary cilia is associated with HIR-induced AKI and that the presence of ciliary
      proteins in the urine could be a potential indication of kidney injury.

PMID- 28495529
TI  - MEK/ERK- and calcineurin/NFAT-mediated mechanism of cerebral hyperemia and brain
      injury following NMDA receptor activation.
AB  - N-methyl-d-aspartate (NMDA) receptor activation increases regional cerebral blood
      flow (rCBF) and induces neuronal injury, but similarities between these processes
      are poorly understood. In this study, by measuring rCBF in vivo, we identified a
      clear correlation between cerebral hyperemia and brain injury. NMDA receptor
      activation induced brain injury as a result of rCBF increase, which was
      attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin.
      Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase
      (ERK) and nuclear translocation of nuclear factor of activated T-cell (NFAT) in
      neurons. Therefore, a MEK/ERK- and calcineurin/NFAT-mediated mechanism of
      neurovascular coupling underlies the pathophysiology of neurovascular disorders.

PMID- 28495530
TI  - Erythrocyte membrane nanoparticles improve the intestinal absorption of
      paclitaxel.
AB  - Paclitaxel (PTX) is a cytotoxic chemotherapy drug with encouraging activity in
      human malignancies. However, free PTX has a very low oral bioavailability due to
      its low aqueous solubility and the gastrointestinal drug barrier. In order to
      overcome this obstacle, we have designed erythrocyte membrane nanoparticles
      (EMNP) using sonication method. The permeability of PTX by EMNP was 3.5-fold
      (Papp = 0.425 nm/s) and 16.2-fold (Papp = 394.1 nm/s) higher than free PTX in
      MDCK-MDR1 cell monolayers and intestinal mucosal tissue, respectively. The in
      vivo pharmacokinetics indicated that the AUC0-t (MUg/mL.h) and Cmax (MUg/mL) of
      EMNP were 14.2-fold and 6.0-fold higher than that of free PTX, respectively. In
      summary, the EMNP appears to be a promising nanoformulation to enhance the oral
      bioavailability of insoluble and poorly permeable drugs.

PMID- 28495531
TI  - The forkhead-like transcription factor (Fhl1p) maintains yeast replicative
      lifespan by regulating ribonucleotide reductase 1 (RNR1) gene transcription.
AB  - In eukaryotes, numerous genetic factors contribute to the lifespan including
      metabolic enzymes, signal transducers, and transcription factors. As previously
      reported, the forkhead-like transcription factor (FHL1) gene was required for
      yeast replicative lifespan and cell proliferation. To determine how Fhl1p
      regulates the lifespan, we performed a DNA microarray analysis of a heterozygous
      diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which
      were then screened for lifespan-regulating activity. We identified the
      ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative
      lifespan. RNR1 encodes a large subunit of the RNR complex, which consists of two
      large (Rnr1p/Rnr3p) and two small (Rnr2p/Rnr4p) subunits. Heterozygous deletion
      of FHL1 reduced transcription of RNR1 and RNR3, but not RNR2 and RNR4. Chromatin
      immunoprecipitation showed that Fhl1p binds to the promoter regions of RNR1 and
      RNR3. Cells harboring an RNR1 deletion or an rnr1-C428A mutation, which abolishes
      RNR catalytic activity, exhibited a short lifespan. In contrast, cells with a
      deletion of the other RNR genes had a normal lifespan. Overexpression of RNR1,
      but not RNR3, restored the lifespan of the heterozygous FHL1 mutant to the wild
      type (WT) level. The Deltafhl1/FHL1 mutant conferred a decrease in dNTP levels
      and an increase in hydroxyurea (HU) sensitivity. These findings reveal that Fhl1p
      regulates RNR1 gene transcription to maintain dNTP levels, thus modulating
      longevity by protection against replication stress.

PMID- 28495533
TI  - MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of
      Huntington's disease.
AB  - Huntington's disease (HD) is a fatal genetic disease caused by abnormal
      aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation
      decreases cell death of the brain and is a promising therapeutic strategy of HD.
      MicroRNAs are short non-coding nucleotides which modulate various genes and
      dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be
      reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance
      protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs),
      we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt
      aggregation. R6/2-derived NSCs can be differentiated under condition of growth
      factor deprivation, and the progression of differentiation leads to a decrease of
      MDR-1 level and efflux function of cells. Immunocytochemistry result also
      confirmed that mHtt aggregation was increased with differentiation. We
      transfected miR-27a in the R6/2-derived differentiated NSCs, and examined
      phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in
      reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can
      transport mHtt, protein level was increased by miR-27a transfection. Conversely,
      knock-down of MDR-1 through MDR-1 siRNA increased mHtt aggregation in vitro. Our
      results indicate that miR-27a could reduce mHtt level of the HD cell by
      augmenting MDR-1 function.

PMID- 28495534
TI  - Hybrid Treatment of the Aberrant Right Subclavian Artery (Arteria Lusoria):
      Feasibility Study on 180 Angio-CTs.
AB  - BACKGROUND: The aberrant right subclavian artery or arteria lusoria (AL) is the
      most frequent anatomical variation of the supra-aortic trunks (SAT). Treatment is
      only warranted in the presence of an aneurysm because of the risk of rupture, or
      in symptomatic cases with signs of compression of the esophagus or the trachea,
      with embolisms causing right upper limb ischemia of vertebrobasilar
      cerebrovascular accidents. The conventional surgical treatment of AL is the
      closure of the origin of AL and the revascularization of the right subclavian
      artery through a left thoracotomy. With the appearance of endovascular
      techniques, some of these patients can be treated with minimally invasive hybrid
      techniques. The aim of this study is to evaluate the feasibility of the
      endovascular treatment of AL based on the radioanatomical analysis of the
      thoracic angio-computed tomographies. METHODS: We analyzed 180 thoracic angio
      computed tomographies using millimeter cuts (<1.2 mm) performed between 2010 and
      2015 in the Nancy University Hospital in which an AL was fortuitously discovered.
      Symptomatic ALs and pediatric patients were excluded. The diameters of the SATs
      and the aorta and the distances between the SATs were measured. The data were
      processed with the t-test using the SPSS 22 software. RESULTS: Our results showed
      the presence of a Kommerell diverticulum in 36 cases (20%) and of a bi-carotid
      trunk in 91 cases (50.5%). The average distance between the left subclavian
      artery (LSCA) and AL was 5.4 +/- 4.3 mm. To obtain a proximal neck >20 mm for the
      implantation of a thoracic stent graft, a double transposition or bypass was
      always necessary (LSCA to left common carotid artery, AL to right common
      carotid). An additional debranching of the left common carotid artery was
      necessary in 33.8% of the cases and of all the SATs in 2.9% of the cases.
      CONCLUSIONS: The radio-anatomical study showed that no patient was eligible for
      conventional thoracic endovascular aneurysm repair to treat an aneurysmal AL. The
      hybrid approach is feasible using a double transposition or a bypass before the
      implantation of a stent graft, if needed associated with a debranching of the
      common carotid arteries.

PMID- 28495532
TI  - New insights into the role of mitochondrial calcium homeostasis in cell
      migration.
AB  - Mitochondria are dynamic organelles involved in numerous physiological functions.
      Beyond their function in ATP production, mitochondria regulate cell death,
      reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria
      also play a key role in the buffering of cytosolic calcium, and calcium
      transported into the matrix regulates mitochondrial metabolism. Recently, the
      identification of the mitochondrial calcium uniporter (MCU) and associated
      regulators has allowed the characterization of new physiological roles for
      calcium in both mitochondrial and cellular homeostasis. Indeed, recent work has
      highlighted the importance of mitochondrial calcium homeostasis in regulating
      cell migration. Cell migration is a property common to all metazoans and is
      critical to embryogenesis, cancer progression, wound-healing and immune
      surveillance. Previous work has established that cytoplasmic calcium is a key
      regulator of cell migration, as oscillations in cytosolic calcium activate
      cytoskeletal remodelling, actin contraction and focal adhesion (FA) turnover
      necessary for cell movement. Recent work using animal models and in cellulo
      experiments to genetically modulate MCU and partners have shed new light on the
      role of mitochondrial calcium dynamics in cytoskeletal remodelling through the
      modulation of ATP and ROS production, as well as intracellular calcium
      signalling. This review focuses on MCU and its regulators in cell migration
      during physiological and pathophysiological processes including development and
      cancer. We also present hypotheses to explain the molecular mechanisms by which
      MCU may regulate mitochondrial dynamics and motility to drive cell migration.

PMID- 28495535
TI  - Endoluminal Dilation Technique to Remove Stuck Port-A-Cath: A Case Report.
AB  - Port-a-cath is a type of central venous catheter (CVC) designed to allow repeated
      access to the venous system for parenteral delivery of medications, fluids, and
      nutritional solutions and for sampling venous blood. After years of use or in
      case of damage, CVC must be removed and eventually replaced: the recovery of the
      device should normally be easy, with a small surgical incision of the skin and
      tissues surrounding the device and pulling the catheter. Sometimes, scar tissue
      can develop around the device, making it resistant to removal even after
      application of forceful traction. We report a case of stuck port-a-cath that was
      extracted by using endoluminal dilatation technique.

PMID- 28495536
TI  - Neoaortoiliac System Procedure to Treat Infected Aortic Grafts.
AB  - BACKGROUND: The aim of this case series is to report the results of our center in
      the surgical treatment of infected abdominal aortic grafts using the
      neoaortoiliac system (NAIS) procedure. METHODS: Four male and 2 female patients
      underwent an NAIS repair after endovascular (n = 3), open (n = 2), or combined
      surgery (n = 1) in our center. Mean age was 73 +/- 5.2 years. Graft infection was
      diagnosed by computed tomography angiography (CTA), and only in 2 cases further
      imaging was necessary. The diagnosis was set at average 6.2 years after the
      initial procedure. RESULTS: Four patients underwent a standard pantaloon NAIS
      procedure, 1 patient with a small aortic diameter received 1 femoral vein as
      aortoaortic interposition graft, and 1 patient received a unilateral aortoiliac
      bypass; all patients received autologous femoral veins grafts. Thirty-day
      mortality was zero, with in-hospital mortality of 1 patient (16.7%). Mean
      hospital stay was 27 +/- 4.9 days, with mean intensive care unit stay of 2.2 days
      (range: 1-3). During follow-up (mean: 6.17 months, range: 1-24 months), 2
      patients presented with thigh wound complications, one of which required surgical
      revision. One patient was readmitted due to upper gastrointestinal (GI) bleeding
      as a side effect of anticoagulation, without the presence of ulcer or other GI
      pathology. CONCLUSIONS: In our early experience, NAIS showed to be a demanding
      procedure for both the patient and the surgical team. It avoids however the
      disadvantages of extra-anatomic bypass and other methods used to treat aortic
      graft infection. Larger study groups are necessary to support these findings.

PMID- 28495537
TI  - Impact of Nutritional State on Critical Limb Ischemia Early Outcomes (DENUCRITICC
      Study).
AB  - BACKGROUND: Despite current progress, the prognosis of critical limb ischemia
      (CLI) remains poor. The ageing of the population, the increasing prevalence of
      diabetes mellitus, and the stability of tobacco use will increase the prevalence
      of CLI. CLI patients have risk factors for malnutrition, and the impact of
      malnutrition on morbidity and mortality has been demonstrated in the general
      population. However, we have little information on the consequences of
      undernutrition in the CLI population. The aim of this study is to assess the
      impact of malnutrition on the early outcomes in CLI patients. METHODS: This is a
      double-center prospective study that included all consecutive hospitalized
      patients with CLI. All patients were screened for malnutrition and divided into 2
      groups: severe malnourished patients (group A) and moderate malnourished and well
      nourished (group B). This distribution was based on age-indexed clinical and
      biological data and the patient's general condition: the Nutritional Risk Index
      for patients younger than 75 years, the Mini Nutritional Assessment, or the
      Geriatric Nutritional Risk Index for those older than 75 years. The primary end
      point was defined as the rate of 30-day death. Outcomes were compared in a
      univariate analysis. Stepwise logistic regression was used for the multivariate
      analysis. Variables with a P value <0.2 in the univariate analysis were
      introduced in the multivariate model. RESULTS: We included 106 patients. The
      prevalence of malnutrition was 75.5%, divided into moderate malnutrition (51.9%)
      and severe malnutrition (23.6%). Six patients (24%) died in group A compared with
      8 in group B (4.9%) (P = 0.01). By univariate analysis, severe malnutrition was
      the only factor associated with death at 30 days. By stepwise logistic
      regression, severe malnutrition (odds ratio 6.1, 95% confidence interval 1.6
      23.7, P = 0.006) was found to be the significant risk factors for death at 30
      days. CONCLUSIONS: This study is the first to demonstrate prospectively the major
      importance of malnutrition in the early prognosis of CLI patients.

PMID- 28495538
TI  - Clinical Outcome of Carotid Artery Stenting According to Provider Specialty and
      Volume.
AB  - BACKGROUND: Several studies have demonstrated better outcomes for carotid
      endarterectomy with high-volume hospitals and providers. However, only a few
      studies have reported on the impact of operator specialty/volume on the
      perioperative outcome of carotid artery stenting (CAS). This study will analyze
      the correlation of CAS outcomes and provider specialty and volume. METHODS:
      Prospectively collected data of CAS procedures done at our institution during a
      10-year period were analyzed. Major adverse events (MAEs; 30-day stroke,
      myocardial infarction, and death) were compared according to provider specialty
      (vascular surgeons [VSs], interventional cardiologists [ICs], interventional
      radiologists [IRs], interventional vascular medicine [IVM]), and volume (>=5
      CAS/year vs. <5 CAS/year). RESULTS: Four hundred fourteen CAS procedures (44% for
      symptomatic indications) were analyzed. Demographics/clinical characteristics
      were somewhat similar between specialties. MAE rates were not significantly
      different between various specialties: 3.1% for IC, 6.3% for VS, 7.1% for IR,
      6.7% for IVM (P = 0.3121; 6.3% for VS and 3.8% for others combined, P = 0.2469).
      When physicians with <5 CAS/year were excluded: the MAE rates were 3.1% for IC,
      4.7% for VS, and 6.7% for IVM (P = 0.5633). When VS alone were compared with
      others, and physicians with <5 CAS/year were excluded, the MAE rates were 4.7%
      for VS vs. 3.6% for non-VS (P = 0.5958). The MAE rates for low-volume providers,
      regardless of their specialty, were 9.5% vs. 4% for high-volume providers (P =
      0.1002). Logistic regression analysis showed that the odds ratio of MAE was 0.4
      (0.15-1.1, P = 0.0674) for high-volume providers, while the odds ratio for VS was
      1.3 (0.45-3.954, P = 0.5969). CONCLUSIONS: Perioperative MAE rates for CAS were
      similar between various providers, regardless of specialties, particularly for
      vascular surgeons with similar volume to nonvascular surgeons. Low-volume
      providers had higher MAE rates.

PMID- 28495539
TI  - Ureteroarterial Fistulas: Diagnosis, Management, and Clinical Evolution.
AB  - BACKGROUND: Ureteroarterial fistulas (UAFs) have a low incidence but are a
      potentially fatal cause of hematuria. Initially treated by open surgery,
      endovascular techniques have decreased potential complications. MATERIAL AND
      METHODS: We present a short series of UAFs (n = 5) treated in our institution in
      the last 10 years: 1 case showed up after aorta-iliac bypass surgery, 1 case
      after endovascular aortic repair and embolization of right hypogastric artery,
      and 3 cases after oncological surgeries. We review the published literature via
      PubMed. RESULTS: The different approaches (2 open and 3 endovascular procedures)
      were based on the clinical situation of the patients and on technical
      limitations. Three patients died after the procedure (2 after open surgery and 1
      after endovascular treatment). In our institution, endovascular treatment showed
      good results in terms of early complications and associated mortality compared
      with open surgery. CONCLUSIONS: UAF is a rare but a potentially fatal
      complication in patients with predisposing factors. No long-term follow-up has
      been published to assess the possible complications arising from the technique,
      such as prosthetic infection. No antibiotic treatment protocols have been
      established, so long-term follow-up is necessary to determine late complications.

PMID- 28495540
TI  - Results of the French Multicentric Study of ANACONDATM Fenestrated Endografts in
      the Treatment of Complex Aortic Pathologies (EFEFA Registry).
AB  - BACKGROUND: Most of the experience on fenestrated endovascular aneurysm repair
      involves the custom-made Zenith(r) endograft (Cook). The fenestrated Anaconda(r)
      endograft (Vascutek) was introduced with the potential advantages of complete
      repositioning and lack of stent material on the main aortic body for more
      versatility. However, few data are available. Our objective was to assess its mid
      term results in the treatment of complex aortic aneurysms. METHODS: Consecutive
      patients treated with the custom-made fenestrated Anaconda endograft in France
      and the Principality of Monaco, from December 2010 to October 2015, were
      included. RESULTS: Eighty-six patients were included over 16 centers (82 men,
      mean age 73.4 +/- 8.1 years, 16 (18.6%) symptomatic aneurysms). The repositioning
      system was used in 68 cases (79.1%). Two hundred ninety-two visceral/renal
      vessels were targeted, with a mean number of 3.4 +/- 0.6 target vessels/patient
      and a successful reconstruction in 99.3% of the cases (290/292 vessels).
      Perioperative technical success was achieved in 86.0% (74/86 patients). In
      hospital and 30-day mortality rates were 3.5% (3 patients) and 7.0% (6 patients),
      respectively. At 12 and 24 months, estimated overall survival rate was 88.3% and
      85.2%, target vessel's patency rate was 97.2% and 96.3%, and freedom from
      aneurysm-related reintervention rate was 96.3% and 88.0%, respectively. At 24
      months, there were 7 type II endoleaks (12.7%) and a significant reduction in
      aneurysm maximum transverse diameter in 70.4%. Five limb occlusions occurred at 1
      year and 1 at 2-year follow-up (7.0%). CONCLUSIONS: The fenestrated Anaconda
      stent-graft system offers acceptable technical success rates, mid-term efficacy,
      and durability with respect to aneurysm sac regression, target vessel patency,
      overall mortality, and reintervention rates. Long-term results are still awaited,
      until then, the rate of graft limb occlusion is of concern and should be further
      investigated, especially in case of particularly complex aortic anatomies.

PMID- 28495541
TI  - Endovascular Repair of a Short Neck Abdominal Aortic Aneurysm with a Physician
      Modified Vascutek Anaconda Stent Graft.
AB  - An 81-year-old woman was referred for the treatment of a 79-mm-diameter short
      neck abdominal aortic aneurysm with highly tortuous iliac arteries. She was
      considered at high risk for open repair and not suitable for standard
      endovascular repair given the short length of the proximal neck. Delay for a
      manufactured custom-made fenestrated stent graft was too long given the diameter
      of the aneurysm. A flexible stent graft was preferred because of severe iliac
      tortuosity. Endovascular repair was performed using a physician-modified Anaconda
      stent graft with 1 fenestration for the left renal artery. The technique for
      device modification and implantation is described. Postoperative course was
      uneventful and 1-year computed tomography scan showed complete exclusion of the
      aneurysm sac and patent left renal artery.

PMID- 28495542
TI  - Endothelial Function Is Preserved in Veins Harvested by Either Endoscopic or
      Surgical Techniques.
AB  - BACKGROUND: Endoscopic vein harvest for lower extremity arterial bypass grafting
      has been questioned due to concern for endothelial damage during procurement. We
      sought to compare nitric oxide (NO)-mediated endothelial-dependent relaxation
      (EDR) in vein segments harvested using open surgical techniques (OH) versus
      endoscopic vein harvest (EH) techniques. METHODS: Saphenous vein segments were
      harvested for lower extremity bypass, and a single, minimally handled section of
      saphenous vein, free of branches, was taken from the end of the graft. Four 4-mm
      venous ring segments were then cut and mounted on force transducers. Segments
      were mounted in 37 degrees  oxygenated Krebs-Henseleit solution and maximally
      contracted using KCl. Individual ring segments that did not react to KCl were
      excluded from the study. Norepinephrine (NE) was used to achieve submaximal
      contraction. EDR was determined using increasing concentrations of bradykinin
      (BDK). Endothelial-independent relaxation (EIR) was confirmed using sodium
      nitroprusside. Two-way analysis of variance (ANOVA) was used to analyze
      differences between harvest techniques across BDK concentration and a Student's t
      test was used to analyze single comparisons. RESULTS: Vein segments harvested
      from patients (n = 13) led to 28 viable rings that exhibited a positive reaction
      to KCl (11 rings; 5 patients EH vs. 17 rings; 8 patients OH). Both vein groups
      achieved moderate relaxation to maximal BDK concentration, [10-6 M]; (49.5% EH
      vs. 40.55% OH, P = 0.270). Analysis by 2-way ANOVA for mean % relaxation for BDK
      concentration [10-11-10-6 M] showed improved EDR in EH samples compared with OH
      (P = 0.029). Mean nitrite/nitrate (NO(x)) tissue bath concentration measurements
      post-BDK were 139.8 nM (EH) vs. 97.2 nM (OH; P = 0.264). Histology and positive
      factor VIII immunohistochemistry staining provided evidence for the presence of
      intact endothelium in our sample segments. EIR was preserved and was similar in
      the two groups. CONCLUSIONS: Endothelial function is preserved when utilizing
      endoscopic harvesting techniques. The advantages of minimally invasive vein
      procurement for lower extremity bypass can be obtained without concern for
      damaging venous endothelium.

PMID- 28495543
TI  - Trans-pericardal Color Doppler Ultra Sound to Assess Blood Flow in the Visceral
      Branches during Type A Dissection Procedures Complicated with Mesenteric
      Malperfusion.
AB  - Aortic dissection is a complex disease associated with high mortality and
      morbidity. Among the different possible clinical presentations, type A aortic
      dissection complicated at the onset by mesenteric malperfusion is characterized
      by poor outcome compared with patients not presenting such complication. We
      report the case of a patient with acute type A aortic dissection presenting with
      mesenteric malperfusion, in whom trans-pericardial color Doppler ultrasound
      (CDUS) examination was used to assess intraoperative and postoperative blood flow
      in the mesenteric artery. Trans-pericardial CDUS is demonstrated as a fast and
      simple diagnostic method with a good matching compared with contrast-enhanced
      computed tomography scan imaging, if correctly approached. We believe that this
      technique could be an important adjunctive tool for the intraoperative and
      perioperative management and decision-making in all patients with type A
      dissection presenting with mesenteric ischemia.

PMID- 28495545
TI  - Asymptotic tracking and disturbance rejection of the blood glucose regulation
      system.
AB  - Type 1 diabetes patients need external insulin to maintain blood glucose within a
      narrow range from 65 to 108 mg/dl (3.6 to 6.0 mmol/l). A mathematical model for
      the blood glucose regulation is required for integrating a glucose monitoring
      system into insulin pump technology to form a closed-loop insulin delivery system
      on the feedback of the blood glucose, the so-called "artificial pancreas". The
      objective of this paper is to treat the exogenous glucose from food as a glucose
      disturbance and then develop a closed-loop feedback and feedforward control
      system for the blood glucose regulation system subject to the exogenous glucose
      disturbance. For this, a mathematical model for the glucose disturbance is
      proposed on the basis of experimental data, and then incorporated into an
      existing blood glucose regulation model. Because all the eigenvalues of the
      disturbance model have zero real parts, the center manifold theory is used to
      establish blood glucose regulator equations. We then use their solutions to
      synthesize a required feedback and feedforward controller to reject the
      disturbance and asymptotically track a constant glucose reference of 90  mg/dl.
      Since the regulator equations are nonlinear partial differential equations and
      usually impossible to solve analytically, a linear approximation solution is
      obtained. Our numerical simulations show that, under the linear approximate
      feedback and feedforward controller, the blood glucose asymptotically tracks its
      desired level of 90 mg/dl approximately.

PMID- 28495544
TI  - Modeling glucose metabolism and lactate production in the kidney.
AB  - The metabolism of glucose provides most of the ATP required for energy-dependent
      transport processes. In the inner medulla of the mammalian kidney, limited blood
      flow and O2 supply yield low oxygen tension; therefore, a substantial fraction of
      the glucose metabolism in that region is anaerobic. Lactate is considered to be a
      waste product of anaerobic glycolysis, which yields two lactate molecules for
      each glucose molecule consumed, thereby likely leading to the production and
      accumulation of a significant amount of lactate in the inner medulla. To gain
      insights into the transport and metabolic processes in the kidney, we have
      developed a detailed mathematical model of the renal medulla of the rat kidney.
      The model represents the radial organization of the renal tubules and vessels,
      which centers around the vascular bundles in the outer medulla and around
      clusters of collecting ducts in the inner medulla. Model simulations yield
      significant radial gradients in interstitial fluid oxygen tension and glucose and
      lactate concentrations in the outer medulla and upper inner medulla. In the deep
      inner medulla, interstitial fluid concentrations become much more homogeneous, as
      the radial organization of tubules and vessels is not distinguishable. Using this
      model, we have identified parameters concerning glucose transport and basal
      metabolism, as well as lactate production via anaerobic glycolysis, that yield
      predicted blood glucose and lactate concentrations consistent with experimental
      measurements in the papillary tip. In addition, simulations indicate that the
      radial organization of the rat kidney may affect lactate buildup in the inner
      medulla.

PMID- 28495546
TI  - Subcortical brain volume differences in participants with attention deficit
      hyperactivity disorder in children and adults.

PMID- 28495547
TI  - Corrections.

PMID- 28495548
TI  - Subcortical brain volume differences in participants with attention deficit
      hyperactivity disorder in children and adults - Authors' reply.

PMID- 28495550
TI  - Subcortical brain volume differences in participants with attention deficit
      hyperactivity disorder in children and adults.

PMID- 28495549
TI  - A blind spot on the global mental health map: a scoping review of 25 years'
      development of mental health care for people with severe mental illnesses in
      central and eastern Europe.
AB  - Just over 25 years have passed since the major sociopolitical changes in central
      and eastern Europe; our aim was to map and analyse the development of mental
      health-care practice for people with severe mental illnesses in this region since
      then. A scoping review was complemented by an expert survey in 24 countries.
      Mental health-care practice in the region differs greatly across as well as
      within individual countries. National policies often exist but reforms remain
      mostly in the realm of aspiration. Services are predominantly based in
      psychiatric hospitals. Decision making on resource allocation is not transparent,
      and full economic evaluations of complex interventions and rigorous
      epidemiological studies are lacking. Stigma seems to be higher than in other
      European countries, but consideration of human rights and user involvement are
      increasing. The region has seen respectable development, which happened because
      of grassroots initiatives supported by international organisations, rather than
      by systematic implementation of government policies.

PMID- 28495551
TI  - Subcortical brain volume differences in participants with attention deficit
      hyperactivity disorder in children and adults.

PMID- 28495552
TI  - Subcortical brain volume differences in participants with attention deficit
      hyperactivity disorder in children and adults.

PMID- 28495554
TI  - Collecting duct carcinoma of the kidney: Disease characteristics and treatment
      outcomes from the National Cancer Database.
AB  - OBJECTIVE: To use a large population-level database to assess survival outcomes
      for collecting duct renal cell carcinoma (CDRCC). MATERIALS AND METHODS: The
      National Cancer Database was queried for all cases of CDRCC and clear cell renal
      cell carcinoma (CCRCC) from 2004 to 2013. After removing patients with other
      cancer diagnoses, the analytic cohort was composed of 201,686 CCRCC and 577 CDRCC
      cases. Kaplan-Meier and cox proportional hazards analysis were employed to model
      survival. RESULTS: Compared to CCRCC, patients with CDRCC presented with higher
      grade and stage, node positive, and metastatic disease (70.7% vs. 30.0% with
      metastasis; P<0.001). Overall median survival for CDRCC was 13.2 months (95% CI:
      11.0-15.5) compared to the 122.5 months (95% CI: 121.0-123.9) for CCRCC. On
      multivariate analysis of the CDRCC cohort, increasing T stage, high-grade
      disease, and metastasis were predictors of mortality. Of 184 patients with
      metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) whereas the rest
      were treated with chemo/radiation or observed. Survival outcomes were improved in
      patients who received both CNx with chemo/radiation compared to CNx alone (hazard
      ratio = 0.51, 95% CI: 0.32-0.79) or chemo/radiation alone (hazard ratio = 0.57,
      95% CI: 0.37-0.89) on multivariate analysis. CONCLUSION: CDRCC is an aggressive
      subtype of renal cell carcinoma. Median survival is 13 months after diagnosis,
      drastically lower than for CCRCC. More than 70% of patients have metastatic
      disease at diagnosis. Chemo/radiation in addition to CNx is associated with a
      survival benefit over single mode therapy.

PMID- 28495553
TI  - The expanding repertoire of targets for immune checkpoint inhibition in bladder
      cancer: What lies beneath the tip of the iceberg, PD-L1.
AB  - Over the last decade, a new understanding of tumor-immune system interplay has
      been ushered in, lead in large part by the discovery of immune checkpoints
      mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1
      immune checkpoint pathway has already shown great success as a cancer
      immunotherapy for advanced urothelial carcinoma, leading to durable clinical
      remissions in an otherwise incurable disease. There are newly described members
      of the B7-CD28 family including B7-H3, B7x, and HHLA2. These ligands are thought
      to play an essential role in suppressing T-cell response, leading to immune
      tolerance of tumors. This feature makes them attractive targets for novel
      immunotherapy treatment paradigms. Here, we review the literature of current
      strategies and future directions of immune checkpoint blockade therapy for
      bladder cancer.

PMID- 28495555
TI  - Oncological and functional outcomes of sexual function-preserving cystectomy
      compared with standard radical cystectomy in men: A systematic review.
AB  - INTRODUCTION: Different sexual function-preserving surgical techniques aimed at
      improving voiding and sexual function in patients undergoing radical cystectomy
      for bladder cancer have been described. The objective of this systematic review
      is to determine the effect of sexual function-preserving cystectomy (SPC) on
      functional and oncological outcomes. MATERIALS AND METHODS: Relevant databases
      were searched covering the time frame 2000 to 2015. All publications presenting
      data on any type of SPC reporting oncological or functional outcomes with a
      minimum follow-up of 1 year were identified. Comparative studies including a
      minimum of 30 patients and single-arm case series with a minimum of 50 patients
      were selected. No language restrictions were applied. RESULTS: In a total of
      8,517 identified abstracts, 12 studies were eligible for inclusion. SPC described
      included prostate-, capsule-, seminal vesicle, and nerve-sparing techniques.
      Local recurrence ranged from 1.2% to 61.1% (vs. 16.0%-55.0% in the control group)
      and metastatic disease from 0% to 33.3% (vs. 33.0%). No differences were found in
      comparative studies reporting oncological outcomes. Postoperative potency was
      significantly better in the SPC groups in 6 studies comparing sexual function
      preserving cystectomy vs. radical cystectomy (P<0.05). No major effect on
      continence was found. Overall, there was moderate to high risk of bias and
      confounding. CONCLUSIONS: The evidence base for prostate-, capsule-, or nerve
      sparing cystectomy suggests that these procedures may yield better sexual
      outcomes than standard cystectomy, without compromising oncological outcomes.
      However, the overall quality of the evidence was moderate, and hence if offered,
      patients must be carefully selected, counseled, and closely monitored.

PMID- 28495556
TI  - Synthesis, crystal structure determination, biological screening and docking
      studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as
      inhibitors of cholinesterases.
AB  - Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry
      out the N1-substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N
      alkylated/benzylated quinazoline derivatives were synthesized, characterized and
      evaluated for their inhibition against cholinesterases. N-alkylation of the
      series of the compounds reported previously (N-unsubstituted) resulted in
      improved activity. All the compounds showed inhibition of both enzymes in the
      micromolar to submicromolar range. Structure activity relationship (SAR) of the
      32 derivatives showed that N-benzylated compounds possess good activity than N
      alkylated compounds. N-benzylated compounds 2ad and 2af were found very active
      with their IC50 values toward AChE in submicromolar range (0.8uM and 0.6uM
      respectively). Binding modes of the synthesized compounds were explored by using
      GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational
      predictions of ADMET studies reveal that all the compounds have good
      pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover,
      all the compounds are predicted to be absorbed in human intestine and also have
      the ability to cross blood brain barrier. Overall, the synthesized compounds have
      established a structural foundation for the design of new inhibitors of
      cholinesterase.

PMID- 28495557
TI  - DNA fluorescent labeling with naphtho[1,2,3-cd]indol-6(2H)-one for investigation
      of protein-DNA interactions.
AB  - Fluorescently labeled DNA to study protein-DNA interactions was synthesized using
      the Cu(I)-catalysed cycloaddition (CuAAC) reaction. For this purpose, a new azido
      containing fluorophore based on the naphtho[1,2,3-cd]indol-6(2H)-one derivative
      was obtained. The fluorescent properties of naphtho[1,2,3-cd]indol-6(2H)-one
      derivatives and labeled DNA were studied. The new fluorescent DNA conjugate was
      shown to be a useful tool to study complex mechanisms of protein-DNA
      interactions.

PMID- 28495558
TI  - Acute psychosocial stress and everyday moral decision-making in young healthy
      men: The impact of cortisol.
AB  - In everyday life, moral decisions must frequently be made under acute stress.
      Although there is increasing evidence that both stress and cortisol affect moral
      judgment and behavior as well as decision-making in various domains unrelated to
      morality, surprisingly few attempts have been made to explore the effects of
      stress on everyday moral decision-making. Therefore, in the present study, we
      exposed 50 young healthy men to the Trier Social Stress Test (TSST) or its non
      stressful placebo version (PTSST). We investigated the impact of acute stress
      exposure and stress-related cortisol levels on decision-making, decision
      certainty, and emotions in 28 everyday moral conflict situations with altruistic
      versus egoistic response alternatives. Results showed that the TSST-exposed group
      made more altruistic decisions than the non-stress control group, while groups
      did not differ in decision certainty and emotion ratings. Moreover, in
      correlational as well as regression analyses, additionally controlling for
      confounding variables, we observed significant positive associations between
      cortisol levels and altruistic decision-making. Further analyses revealed that
      altruistic decisions came along with significantly higher decision certainty and
      significantly more positive emotion ratings than egoistic decisions. Notably, our
      data also raise the idea that the personality trait agreeableness plays an
      important role in everyday moral decision-making. In sum, our findings provide
      initial evidence that both acute stress exposure and cortisol levels have
      prosocial effects on everyday moral decision-making in young healthy men.

PMID- 28495560
TI  - Characterization of two cryptic plasmids from Kocuria palustris IPUFS-1 and
      construction of novel Escherichia coli-Kocuria shuttle vector for biocatalysis.
AB  - Two cryptic plasmids, designated pKPAL1 and pKPAL2, were identified from the gram
      positive bacterium Kocuria palustris IPUFS-1, which was isolated from a fish
      source. The 2251-bp and 2488-bp circular genomes of pKPAL1 and pKPAL2,
      respectively, were sequenced. Subsequent open reading frame (ORF) and homology
      search analyses suggested that pKPAL1 and pKPAL2 possess two and three ORFs,
      respectively, and encode the putative replication proteins, RepA and RepB, like
      the genomes of several plasmids in gram-positive bacteria. Thus, pKPAL1 and
      pKPAL2 were inferred to belong to the ColE2 plasmid family. We constructed novel
      Escherichia coli-Kocuria shuttle vectors pKITE101-103 based on pKPAL1. The
      constructed shuttle vector was stably maintained in Kocuria transformant cells,
      and vector copy number was estimated to be about 60 per cell. Leifsonia sp. S749
      alcohol dehydrogenase (LSADH) was efficiently expressed in Kocuria rhizophila
      DC2201 using the pKITE103P vector under the control of the promoter of
      glyceraldehyde 3-phosphate dehydrogenase (gapdh). Herein, we demonstrate that the
      novel shuttle vector is a useful tool for developing biocatalysts based on
      organic solvent-tolerant Kocuria cells.

PMID- 28495559
TI  - Influence of adhesive strategy on clinical parameters in cervical restorations: A
      systematic review and meta-analysis.
AB  - OBJECTIVES: We aimed to answer the following PICO question: "Is the risk of
      postoperative sensitivity (POS), retention rates and marginal discoloration of
      composite restorations [CR] bonded with self-etch (SE) in non-carious cervical
      lesions (NCCLs) of adults equals to etch-and-rinse (ER) adhesives?". METHODS: A
      comprehensive search was performed in May 2016 in the MEDLINE, Scopus, Web of
      Science, LILACS, BBO and Cochrane Library and SIGLE, abstracts of IADR,
      unpublished and ongoing trials registries, dissertations and theses without
      restrictions. Only randomized clinical trials that compared composite resin
      restorations placed with self-etch and etch-and-rinse in NCCLs were included.
      After removal of duplicates and non-eligible articles, 50 articles from 42
      studies (follow-ups of the same study were merged) remained for synthesis of the
      risk of bias (Cochrane Risk of bias tool). RESULTS: Thirteen studies were at
      "high" risk of bias, yielding 29 studies for meta-analysis. No difference on the
      POS after restoration placement (risk ratio [RR] 1.04; 95% CI 0.81 to 1.34) as
      well as in the retention rates for all follow-up periods was observed. The etch
      and-rinse approach produced less marginal discoloration at 18 months to 2 years
      (RR 1.51; 95% CI 1.21 to 1.90) and at 4 to 5 years (RR 1.81; 95% CI 1.28 to 2.55)
      (p<0.0007). CONCLUSIONS: The adhesive strategy did not influence the POS and the
      retention rates of composite resin in NCCLs in any of the follow-up periods; but
      less marginal discoloration was found in etch-and-rinse adhesives. CLINICAL
      SIGNIFICANCE: Composite resin restorations placed with self-etch and etch-and
      rinse adhesives produce restoration with the similar clinical service and POS,
      however using etch-and-rinse adhesives one can reduce marginal discoloration.
      PROSPERO registration number: CRD42015019533.

PMID- 28495561
TI  - Function of a thermophilic archaeal chaperonin is enhanced by electrostatic
      interactions with its targets.
AB  - Molecular chaperonin CpkB from Thermococcus kodakarensis possesses a unique
      negatively charged carboxy-terminal region that functions in target protein
      recognition. In the present study, green fluorescent protein (GFP), 4
      oxalocrotonate tautomerase (4OTA) and glutamine:fructose-6-phosphate
      amidotransferase (GFAT) were fused with a positively charged tag, selected using
      docking simulation in silico, to enhance their electrostatic interactions with
      CpkB. Target proteins were heated at 75 degrees C in the presence or absence of
      CpkB, and the remaining enzymatic activity was measured. The half-life (t1/2) of
      the positively charged tagged targets was significantly longer than that of their
      tagless counterparts. Escherichia coli cell extracts containing heterologously
      expressed targets (GFP, 4OTA and GFAT and their tagged variants) were incubated
      at 75 degrees C in the presence or absence of CpkB, and the proportion remaining
      in the soluble fraction was evaluated by SDS-PAGE. Only positively charged tagged
      targets remained predominantly in the soluble fraction in the presence of CpkB
      but not in the absence of CpkB. When tagless or negatively charged tagged targets
      were employed, the targets were barely detected in the soluble fraction,
      suggesting that CpkB protected positively charged tagged proteins more
      efficiently than tagless targets. Attachment of a positively charged tag may be a
      generally applicable method for enhancing target recognition by chaperonins
      carrying negatively charged carboxy-terminal regions, such as the archaeal
      chaperonin CpkB.

PMID- 28495563
TI  - Resistance matters in EARNEST.

PMID- 28495564
TI  - Characterization of Toll-like receptor 22 in turbot (Scophthalmus maximus).
AB  - Toll-like receptors (TLRs) are essential for activation of the innate immune
      system in response to invading pathogens. In this paper, expression profiles of
      the turbot (Scophthalmus maximus) TLR22 gene (tbTLR22) were analyzed with RT-PCR
      and in situ hybridization. Then its expression patterns simulated with ligands or
      pathogens were investigated. Streptococcus iniae, Edwardsiella tarda, Hirame
      rhabdovirus virus (HIRRV), polyinosinic: polycytidylic acid (Poly I:C),
      peptidoglycan (PGN), or lipopolysaccharides (LPS) was injected to turbot; poly
      I:C, PGN, or LPS was added into cultured peripheral blood leukocytes (PBL); and
      then the tbTLR22 in liver, spleen, gill, kidney and cultured PBL was measured
      using Quantitative PCR. The recombinant protein of tbTLR22 (rp-tbTLR22) and its
      antibody were produced, then the reactions of antibody to tissues were detected
      by Western-blotting, and the binding of rp-tbTLR22 to all the stimulants was
      detected using ELISA. The results showed tbTLR22 expression was significantly up
      regulated by PolyI: C, but no significant change in PGN and LPS groups; tbTLR22
      significantly increased in liver and spleen after S. iniae infection with the
      maximum of 3.6 times and 3.3 times; in liver and kidney after E. tarda infection
      with the maximum of 3.4 times and 4.1 times; and then in gill and kidney after
      HIRRV infection by 4.8 and 4.1 times. Rp-tbTLR22 antibody could recognize the
      total protein from liver, kidney, gill and spleen at 40 kDa, 90 kDa and 120 kDa,
      respectively. The rp-tbTLR22 could bind to three ligands and pathogens in vitro.
      The expression and reaction data gave a clear recognization model of tbTLR22.

PMID- 28495565
TI  - On the Post-Compaction Evolution of Tensile Strength of Sodium Chloride-Starch
      Mixture Tablets.
AB  - This study focuses on the evolution of mechanical behavior of starch and sodium
      chloride (NaCl) mixture tablets after compaction. This type of mixture has
      attracted attention in the past because such tablets exhibit lower tensile
      strengths than the ones of its individual components. Here we demonstrate that
      the strengths of NaCl-starch mixtures and NaCl tablets evolve after compaction in
      an opposite way. When stored at relative humidity of 60%, NaCl tablets strengthen
      with time, whereas NaCl-starch mixtures weaken. To explain this behavior, we
      propose that in the NaCl-starch mixture, the presence of 2 materials with
      significantly different elastic moduli leads to creation of tensile stresses at
      the stiffer NaCl-NaCl contacts. Such tensile stresses lead to a reduction in
      strength of the compacted mixtures by negating a local dissolution
      reprecipitation mechanism, which strengthens the NaCl-NaCl in pure NaCl tablet.
      This effect is proven by experimental results from NaCl specimens diametrically
      loaded during storage.

PMID- 28495566
TI  - The Constraints, Construction, and Verification of a Strain-Specific
      Physiologically Based Pharmacokinetic Rat Model.
AB  - The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically
      incorporated within physiologically based pharmacokinetic (PBPK) models, can
      harness in vitro drug data and enhance understanding of in vivo pharmacokinetics.
      This study's objective was to develop a user-friendly rat (250 g, male Sprague
      Dawley) IVIVE-linked PBPK model. A 13-compartment PBPK model including
      mechanistic absorption models was developed, with required system data
      (anatomical, physiological, and relevant IVIVE scaling factors) collated from
      literature and analyzed. Overall, 178 system parameter values for the model are
      provided. This study also highlights gaps in available system data required for
      strain-specific rat PBPK model development. The model's functionality and
      performance were assessed using previous literature-sourced in vitro properties
      for diazepam, metoprolol, and midazolam. The results of simulations were compared
      against observed pharmacokinetic rat data. Predicted and observed concentration
      profiles in 10 tissues for diazepam after a single intravenous (i.v.) dose making
      use of either observed i.v. clearance (CLiv) or in vitro hepatocyte intrinsic
      clearance (CLint) for simulations generally led to good predictions in various
      tissue compartments. Overall, all i.v. plasma concentration profiles were
      successfully predicted. However, there were challenges in predicting oral plasma
      concentration profiles for metoprolol and midazolam, and the potential reasons
      and according solutions are discussed.

PMID- 28495567
TI  - Transporters Involved in Metformin Pharmacokinetics and Treatment Response.
AB  - Metformin, widely used as first-line treatment for type 2 diabetes, exists
      primarily as a hydrophilic cation at physiological pHs. As such, membrane
      transporters play a substantial role in its absorption, tissues distribution, and
      renal elimination. Multiple organic cation transporters are determinants of the
      pharmacokinetics of metformin, and many of them are important in its
      pharmacological action, as mediators of metformin entry into target tissues.
      Furthermore, a recent genome-wide association study in a large multi-ethnic
      population implicated polymorphisms in SLC2A2, encoding the glucose transporter,
      GLUT2, as important determinants of response to metformin. Here, we describe the
      key transporters associated with metformin pharmacokinetics and response.

PMID- 28495568
TI  - Quantitative Analyses of the Influence of Parameters Governing Rate-Determining
      Process of Hepatic Elimination of Drugs on the Magnitudes of Drug-Drug
      Interactions via Hepatic OATPs and CYP3A Using Physiologically Based
      Pharmacokinetic Models.
AB  - Physiologically based pharmacokinetic models were constructed for hepatic organic
      anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) substrates
      (bosentan, repaglinide, clarithromycin, and simeprevir), a CYP3A probe substrate
      (midazolam), and selective inhibitors for OATPs (rifampicin) and CYP3A
      (itraconazole), although the role of OATPs in the hepatic uptake of
      clarithromycin is unclear. The pharmacokinetic data were obtained from our
      previous clinical drug-drug interaction (DDI) study. Parameters optimized from
      clinical PK data were confirmed to reproduce their blood concentrations in
      control phase. DDIs with rifampicin and itraconazole were simulated using in vivo
      Rdif (ratio of diffusional uptake to active uptake) and beta (the fraction of the
      sum of intrinsic clearances for metabolism and biliary excretion in all possible
      itineraries of intracellular drugs including basolateral efflux) estimated by
      static analyses based on the extended clearance concept, in vivo inhibition
      constant (Ki) for hepatic OATPs reported previously, and in vivo Ki for CYP3A
      determined from DDI data with midazolam and itraconazole. Sensitivity analyses
      showed the magnitudes of DDIs largely depended on Rdif and beta. In conclusion,
      our approach using physiologically based pharmacokinetic modeling showed that the
      rational estimation of parameters governing rate-determining process of hepatic
      elimination is critical to accurately predict DDI magnitudes involving
      OATPs/CYP3A inhibition.

PMID- 28495562
TI  - Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from
      second-line antiretroviral therapy in the public health approach: an
      observational analysis within the randomised, open-label, EARNEST trial.
AB  - BACKGROUND: Cross-resistance after first-line antiretroviral therapy (ART)
      failure is expected to impair activity of nucleoside reverse-transcriptase
      inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for
      the effect of cross-resistance on virological outcomes is limited. We aimed to
      assess the association between the activity, predicted by resistance testing, of
      the NRTIs used in second-line therapy and treatment outcomes for patients
      infected with HIV. METHODS: We did an observational analysis of additional data
      from a published open-label, randomised trial of second-line ART (EARNEST) in sub
      Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line
      ART had failed (assessed by WHO criteria with virological confirmation) were
      randomly assigned to a boosted protease inhibitor (standardised to ritonavir
      boosted lopinavir) with two to three NRTIs (clinician-selected, without
      resistance testing); or with raltegravir; or alone as protease inhibitor
      monotherapy (discontinued after week 96). We tested genotypic resistance on
      stored baseline samples in patients in the protease inhibitor and NRTI group and
      calculated the predicted activity of prescribed second-line NRTIs. We measured
      viral load in stored samples for all patients obtained every 12-16 weeks. This
      trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and
      ClinicalTrials.gov (number NCT00988039). FINDINGS: Baseline genotypes were
      available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group.
      176 (89%) of 198 patients prescribed a protease inhibitor with no predicted
      active NRTIs had viral suppression (viral load <400 copies per mL) at week 144,
      compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir
      group at week 144 (p=0.02) and 233 (61%) of 280 patients in the protease
      inhibitor monotherapy group at week 96 (p<0.0001). Compared with results with no
      active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral
      suppression (p=0.3) and 20 (77%) of 26 patients with two or three active NRTIs
      had viral suppression (p=0.08). Over all follow-up, greater predicted NRTI
      activity was associated with worse viral load suppression (global p=0.0004).
      INTERPRETATION: Genotypic resistance testing might not accurately predict NRTI
      activity in protease inhibitor-based second-line ART. Our results do not support
      the introduction of routine resistance testing in ART programmes in low-income
      settings for the purpose of selecting second-line NRTIs. FUNDING: European and
      Developing Countries Clinical Trials Partnership, UK Medical Research Council,
      Institito de Salud Carlos III, Irish Aid, Swedish International Development
      Cooperation Agency, Instituto Superiore di Sanita, WHO, Merck.

PMID- 28495569
TI  - Plasma Lipidomics of Healthy Japanese Adults Reveals Gender- and Age-Related
      Differences.
AB  - Lipid metabolites in the blood are expected to be biomarker candidates to reflect
      disease states and responses to therapeutic drugs. However, their profiles are
      influenced by subject background, which may lead to confounding results. This
      study aimed to evaluate whether age and gender affect lipid metabolite levels in
      the plasma of healthy Japanese adults. Comprehensive lipidomic analysis was
      performed using liquid chromatography-mass spectrometry for overnight fasted
      volunteers consisting of 4 groups of 15 subjects each: young males (25-35 years),
      elderly males (55-64 years), young females (25-35 years), and elderly females (55
      65 years). Of 326 detected lipids, none showed significant gender-associated
      differences in the young groups and 3 metabolites showed significant gender
      associated differences in the elderly groups, suggesting that age has little
      impact on plasma lipid levels in Japanese subjects. We found age-associated
      differences in 111 (34%) and 115 (35%) metabolites in males and females,
      respectively, indicating that the subjects' age should be considered an important
      confounding factor for lipid biomarker exploration and validation studies in
      Japanese populations. These findings provide fundamental information on biomarker
      discovery, validation, and qualification processes in Japanese populations, and
      facilitate the evaluation of biomarker candidates found in other populations.

PMID- 28495570
TI  - Effect of chronic heart failure in older rats on respiratory muscle and hindlimb
      blood flow during submaximal exercise.
AB  - Submaximal exercise diaphragm blood flow (BF) is elevated in young chronic heart
      failure (CHF) rats, while it is unknown if this occurs in older animals.
      Respiratory and hindlimb muscle BFs (radiolabeled microspheres) were measured at
      rest and during submaximal exercise (20m/min, 5% grade) in older healthy (n=7)
      and CHF (n=6) Fischer 344X Brown Norway rats (27-29 mo old). Older CHF, compared
      to healthy, rats had greater (p<0.01) left ventricular end-diastolic pressure and
      right ventricle and lung weight (normalized to body weight). During submaximal
      exercise, respiratory and hindlimb muscle BFs increased (p<0.02) in both groups,
      while diaphragm BF was higher (CHF: 257+/-32; healthy: 121+/-9mL/min/100g,
      p<0.01) and hindlimb BF lower (CHF: 111+/-10; healthy: 133+/-12mL/min/100g,
      p=0.04) in older CHF compared to healthy rats. Submaximal exercise hindlimb BF
      was negatively related (r=-0.93; p=0.03) to diaphragm BF in older CHF rats.
      During submaximal exercise, diaphragm BF is elevated in older CHF compared to
      healthy rats in proportion to the compromised hindlimb BF.

PMID- 28495571
TI  - Role of iron in the pathogenesis of respiratory disease.
AB  - Iron is essential for many biological processes, however, too much or too little
      iron can result in a wide variety of pathological consequences, depending on the
      organ system, tissue or cell type affected. In order to reduce pathogenesis, iron
      levels are tightly controlled in throughout the body by regulatory systems that
      control iron absorption, systemic transport and cellular uptake and storage.
      Altered iron levels and/or dysregulated homeostasis have been associated with
      several lung diseases, including chronic obstructive pulmonary disease, lung
      cancer, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. However, the
      mechanisms that underpin these associations and whether iron plays a key role in
      the pathogenesis of lung disease are yet to be fully elucidated. Furthermore, in
      order to survive and replicate, pathogenic micro-organisms have evolved
      strategies to source host iron, including freeing iron from cells and proteins
      that store and transport iron. To counter these microbial strategies, mammals
      have evolved immune-mediated defence mechanisms that reduce iron availability to
      pathogens. This interplay between iron, infection and immunity has important
      ramifications for the pathogenesis and management of human respiratory infections
      and diseases. An increased understanding of the role that iron plays in the
      pathogenesis of lung disease and respiratory infections may help inform novel
      therapeutic strategies. Here we review the clinical and experimental evidence
      that highlights the potential importance of iron in respiratory diseases and
      infections.

PMID- 28495572
TI  - A Tumor Ultrasound-guided Incision (TUGI) Approach to Nipple-sparing Mastectomy:
      Balancing Oncologic Safety and Technical Outcomes.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) is a prevalent operation for patients
      with breast cancer. Indications have been limited to tumors accessible via
      radial, infra-mammary, or periareolar incisions out of concern for oncologic and
      technical safety. We study an alternative approach to NSM based on tumor
      ultrasound-guided incisions (TUGI) and report its oncologic and technical
      outcomes. MATERIALS AND METHODS: A retrospective chart review examined patients
      who underwent TUGI NSM between 2013 and 2016. Operative notes, postoperative
      notes, pathology reports, and postoperative photography were analyzed. RESULTS:
      Ninety-four patients had mastectomy with reconstruction performed over a 3-year
      period by the senior authors. Of those, 31 (33%) were NSM and 13 (14%) had the
      TUGI technique, forming the study group. The median tumor size was 1.5 cm, with a
      median distance from the nipple areolar complex of 5 cm. Sixty-two percent of the
      incisions were in the upper quadrants of the breast. Median operative time was
      207 minutes. Zero patients had positive margins. One hundred percent of patients
      underwent immediate tissue expander placement, 46% with acellular dermal matrix.
      For final reconstruction, 23% had a free flap, 69% implant, and 8% are still
      pending. Eight percent of patients had wound infection, and 15% of patients had
      NAC necrosis. No cancer recurrence has been observed at a median follow-up of 17
      months. CONCLUSION: TUGI offers a valuable, oncologically sound alternative
      approach to traditional NSM. The technical results and outcomes support its use
      in selected patients with breast cancer undergoing NSM.

PMID- 28495573
TI  - Spatial mapping of humeral head bone density.
AB  - BACKGROUND: Short-stem humeral replacements achieve fixation by anchoring to the
      metaphyseal trabecular bone. Fixing the implant in high-density bone can provide
      strong fixation and reduce the risk of loosening. However, there is a lack of
      data mapping the bone density distribution in the proximal humerus. The aim of
      the study was to investigate the bone density in proximal humerus. METHODS: Eight
      computed tomography scans of healthy cadaveric humeri were used to map bone
      density distribution in the humeral head. The proximal humeral head was divided
      into 12 slices parallel to the humeral anatomic neck. Each slice was then divided
      into 4 concentric circles. The slices below the anatomic neck, where short-stem
      implants have their fixation features, were further divided into radial sectors.
      The average bone density for each of these regions was calculated, and regions of
      interest were compared using a repeated-measures analysis of variance with
      significance set at P < .05. RESULTS: Average apparent bone density was found to
      decrease from proximal to distal regions, with the majority of higher bone
      density proximal to the anatomic neck of the humerus (P < .05). Below the
      anatomic neck, bone density increases from central to peripheral regions, where
      cortical bone eventually occupies the space (P < .05). In distal slices below the
      anatomic neck, a higher bone density distribution in the medial calcar region was
      also observed. CONCLUSION: This study indicates that it is advantageous with
      respect to implant fixation to preserve some bone above the anatomic neck and
      epiphyseal plate and to use the denser bone at the periphery.

PMID- 28495574
TI  - Does acromioplasty result in favorable clinical and radiologic outcomes in the
      management of chronic subacromial pain syndrome? A double-blinded randomized
      clinical trial with 9 to 14 years' follow-up.
AB  - BACKGROUND: The treatment effect of acromioplasty for chronic subacromial pain
      syndrome (SAPS) on long-term shoulder function and rotator cuff deterioration has
      still to be determined. This study aimed to determine the long-term clinical and
      radiologic treatment effect of arthroscopic acromioplasty in patients with
      chronic SAPS. METHODS: In this double-blind, randomized clinical trial, 56
      patients with chronic SAPS (median age, 47 years; age range, 31-60 years) were
      randomly allocated to arthroscopic bursectomy alone or to bursectomy combined
      with acromioplasty and were followed up for a median of 12 years. The primary
      outcome was the Constant score. Secondary outcomes included the Simple Shoulder
      Test, visual analog scale (VAS) for pain, VAS for shoulder functionality, and
      rotator cuff integrity assessed with magnetic resonance imaging or ultrasound.
      RESULTS: A total of 43 patients (77%) were examined at a median of 12 years'
      follow-up. Intention-to-treat analysis at 12 years' follow-up did not show a
      significant additional treatment effect of acromioplasty on bursectomy alone in
      improvement in Constant score (5 points; 95% confidence interval, -5.1 to 15.6),
      Simple Shoulder Test score, VAS score for pain, or VAS score for shoulder
      function. The prevalence of rotator cuff tears was not significantly different
      between the bursectomy group (17%) and acromioplasty group (10%). CONCLUSIONS:
      There were no relevant additional effects of arthroscopic acromioplasty on
      bursectomy alone with respect to clinical outcomes and rotator cuff integrity at
      12 years' follow-up. These findings bring the effectiveness of acromioplasty into
      question and may support the idea of a more conservative approach in the initial
      treatment of SAPS.

PMID- 28495575
TI  - The relationship between the incidence of adhesive capsulitis and hemoglobin A1c.
AB  - BACKGROUND: Previous studies have shown no correlation between adhesive
      capsulitis and hemoglobin A1c (HbA1c). However, HbA1c is only a measure of short
      term blood sugar control. We created a previously nonvalidated variable,
      cumulative HbA1c, that uses HbA1c values over time to estimate the total disease
      burden a single individual experiences over a period. In this study, we aimed to
      evaluate whether a correlation exists between cumulative HbA1c levels in diabetic
      patients and the prevalence of frozen shoulder. We hypothesized that poor long
      term glucose control would be correlated with increased incidence of adhesive
      capsulitis. METHODS: A retrospective analysis at a single institution was
      performed. Data from all patients from a single institution with any HbA1c values
      were collected. A total of 24,417 patients met the inclusion criteria. A variable
      was created establishing the cumulative magnitude of abnormal HbA1c values over
      time, termed "cumulative HbA1c." Logistic regression analysis was performed to
      determine whether long-term glucose control was predictive of the development of
      adhesive capsulitis. RESULTS: Cumulative HbA1c was positively associated with
      adhesive capsulitis (7.6 * 10-5) (ie, odds ratio of 1.000076). The effect size of
      cumulative HbA1c on adhesive capsulitis was significant; for each unit of time
      that the HbA1c level was greater than 7, there was a 2.77% increase in the risk
      of adhesive capsulitis. DISCUSSION: Cumulative HbA1c was associated with an
      increased incidence of adhesive capsulitis. This finding suggests that the
      effects of diabetes that predispose patients to the development of adhesive
      capsulitis are dose dependent. Patients with worse blood sugar control over a
      longer period are at an increased risk of the development of adhesive capsulitis.

PMID- 28495576
TI  - Quantitative assessment of fatty infiltration and muscle volume of the rotator
      cuff muscles using 3-dimensional 2-point Dixon magnetic resonance imaging.
AB  - BACKGROUND: In patients with rotator cuff tears, muscle degeneration is known to
      be a predictor of irreparable tears and poor outcomes after surgical repair.
      Fatty infiltration and volume of the whole muscles constituting the rotator cuff
      were quantitatively assessed using 3-dimensional 2-point Dixon magnetic resonance
      imaging. METHODS: Ten shoulders with a partial-thickness tear, 10 shoulders with
      an isolated supraspinatus tear, and 10 shoulders with a massive tear involving
      supraspinatus and infraspinatus were compared with 10 control shoulders after
      matching age and sex. With segmentation of muscle boundaries, the fat fraction
      value and the volume of the whole rotator cuff muscles were computed. After
      reliabilities were determined, differences in fat fraction, muscle volume, and
      fat-free muscle volume were evaluated. RESULTS: Intra-rater and inter-rater
      reliabilities were regarded as excellent for fat fraction and muscle volume.
      Tendon rupture adversely increased the fat fraction value of the respective
      rotator cuff muscle (P < .002). In the massive tear group, muscle volume was
      significantly decreased in the infraspinatus (P = .035) and increased in the
      teres minor (P = .039). With subtraction of fat volume, a significant decrease of
      fat-free volume of the supraspinatus muscle became apparent with a massive tear
      (P = .003). CONCLUSION: Three-dimensional measurement could evaluate fatty
      infiltration and muscular volume with excellent reliabilities. The present study
      showed that chronic rupture of the tendon adversely increases the fat fraction of
      the respective muscle and indicates that the residual capacity of the rotator
      cuff muscles might be overestimated in patients with severe fatty infiltration.

PMID- 28495578
TI  - Expression pattern and functional analysis of fundc1 in rare minnow (Gobiocypris
      rarus).
AB  - Fundc1 is a mitochondrial outer membrane protein and plays important roles in
      mitochondria fission and hypoxia-induced mitophagy in mammalian cells. However,
      there is no relevant report of fundc1 in fish. In the present study, we cloned a
      942bp fundc1 cDNA from rare minnow. The cDNA, designated as Grfundc1 cDNA,
      contains an open reading frame (ORF) of 459bp which encodes a polypeptide of 152
      amino acid residues. Comparisons of deduced amino acid sequences demonstrated
      that Grfundc1 was highly homologous with those of other vertebrates. RT-PCR and
      real time PCR detection revealed that the transcripts of Grfundc1 were not
      detectable in the unfertilized eggs and had high levels at blastula and gastrula
      stages. Whole mount in situ hybridization analysis observed that Grfundc1 was
      ubiquitously expressed at early stage and later riched in specific regions, such
      as brain, branchial arch, eye and somite during embryogenesis. Grfundc1 was
      expressed in all the tissues of rare minnow adult, including brain, liver, gill,
      eyes, heart, kidney, intestine, muscle, testis and ovary. The expression of
      Grfundc1 in the brain, gill, heart and eye of rare minnow adult was significantly
      down-regulated by hypoxia. Similar hypoxic response was observed in the rare
      minnow embryos at 48hpf following hypoxia exposure. Functional analysis showed
      that knockdown of Grfundc1 significantly caused defects in the body axis and
      dorsal neural tissues of rare minnow embryos. These results indicate that
      Grfundc1 may play important roles in embryogenesis in fish.

PMID- 28495577
TI  - Delivery of anti-inflammatory peptides from hollow PEGylated poly(NIPAM)
      nanoparticles reduces inflammation in an ex vivo osteoarthritis model.
AB  - Targeted delivery of anti-inflammatory osteoarthritis treatments have the
      potential to significantly decrease undesirable systemic side effects and reduce
      required therapeutic dosage. Here we present a targeted, non-invasive drug
      delivery system to decrease inflammation in an osteoarthritis model. Hollow
      thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been
      synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked
      core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1
      propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive
      loading of an anti-inflammatory mitogen-activated protein kinase-activated
      protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK). The drug
      loaded hollow nanoparticles were effective at delivering a therapeutically active
      dose of KAFAK to bovine cartilage explants, suppressing pro-inflammatory
      interleukin-6 (IL-6) expression after interleukin-1 beta (IL-1beta) stimulation.
      This thermosensitive hollow nanoparticle system provides an excellent platform
      for the delivery of peptide therapeutics into highly proteolytic environments
      such as osteoarthritis.

PMID- 28495579
TI  - A new chemotherapy agent-free theranostic system composed of graphene oxide nano
      complex and aptamers for treatment of cancer cells.
AB  - The common cancer treatment strategies like chemotherapy and radiotherapy are
      nonspecific and can trigger severe side effects by damaging normal cells. So,
      targeted cancer therapies, such as apoptosis induction, have attracted great
      attention in recent years. In this project, two nano-complexes, MUC1 aptamer-NAS
      24 aptamer-Graphene oxide (GO) and MUC1 aptamer-Cytochrome C aptamer-GO, were
      designed to induce cell programmed death in MDA-MB-231 and MCF-7 cells (breast
      cancer cell lines) and to verify the level of apoptosis in both cell lines. MUC1
      aptamer was a molecular recognition probe that led the internalization of two
      nano-complexes into MDA-MB-231 and MCF-7 cells (MUC1 positive cells) but not into
      HepG2 cell (liver cancer cell line, MUC1 negative cells). The apoptosis induction
      relied on binding of NAS-24 aptamer to its target, vimentin, in MDA-MB-231 and
      MCF-7 (target cells) with different levels of vimentin content. The function of
      first nano-complex was confirmed by binding of FAM-labeled cytochrome C aptamer
      to its target (cytochrome C) which was released from mitochondria, based on the
      function of the first nano-complex. Fluorometric analysis and gel retardation
      assay proved the formation of nano-complexes. The results of flow cytometry and
      fluorescence microscopy indicated efficient apoptosis induction just in target
      cells (MDA-MB-231 and MCF-7 cells) but not in non-target cells (HepG2 cell). The
      results of MTT assay also confirmed cell death process. Overall, our results
      proved excellent targeted apoptosis in breast cancer cells by designed nano
      complexes which can be applied as an efficient cancer therapy method.

PMID- 28495580
TI  - Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing
      and able to disrupt Abeta aggregates.
AB  - The formation of extracellular aggregates built up by deposits of beta-amyloid
      (Abeta) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to
      display anti-amyloidogenic activity, not only by inhibiting the formation of new
      Abeta aggregates, but also by disaggregating existing ones. However, the uptake
      of Curcumin into the brain is severely restricted by its low ability to cross the
      blood-brain barrier (BBB). Therefore, novel strategies for a targeted delivery of
      Curcumin into the brain are highly desired. Here, we encapsulated Curcumin as
      active ingredient in PLGA (polylactide-co-glycolic-acid) nanoparticles (NPs),
      modified with g7 ligand for BBB crossing. We performed in depth analyses of
      possible toxicity of these NPs, uptake, and, foremost, their ability to influence
      Abeta pathology in vitro using primary hippocampal cell cultures. Our results
      show no apparent toxicity of the formulated NPs, but a significant decrease of
      Abeta aggregates in response to Curcumin loaded NPs. We thus conclude that brain
      delivery of Curcumin using BBB crossing NPs is a promising future approach in the
      treatment of AD.

PMID- 28495581
TI  - Dipicolinic acid as a novel spore-inspired excipient for antibody formulation.
AB  - Ionic excipients are commonly used in aqueous therapeutic monoclonal antibody
      (mAb) formulations. Novel excipients are of industrial interest, with a recent
      focus on Arg salt forms and their application as viscosity reducing and
      stabilizing additives. Here, we report that the calcium salt of dipicolinic acid
      (DPA, pyridine-2,6-dicarboxylic acid), uniquely present in nature in the core of
      certain bacterial spores, reduces the viscosity of a mAb formulated at 150mg/mL,
      below that achieved by Arg hydrochloride at the same concentration (10mM). DPA
      also reduced the reversible phase separation of the same formulation, which
      characteristically occurs for this mAb upon cooling to 4 degrees C. Differential
      scanning calorimetry and differential scanning fluorimetry did not reveal a
      conformation destabilisation of the mAb in the presence of 10mM DPA, or by the
      related quinolinic acid (QA, pyridine-2,3-dicarboxylic acid). However,
      fluorescence spectrophotometry did reveal localised (aromatic) conformational
      changes to the mAb attributed to DPA, dependent on the salt form. While precise
      mechanisms of action remain to be identified, our preliminary data suggest that
      these DPA salts are worthy of further investigation as novel ionic excipient for
      biologics formulation.

PMID- 28495582
TI  - Evaluation of lipid-stabilised tripropionin nanodroplets as a delivery route for
      combretastatin A4.
AB  - Lipid-based nanoemulsions are a cheap and elegant route for improving the
      delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have
      promise for the delivery of different therapeutic agents. Although multiple
      studies have investigated the effects of the oil and preparation conditions on
      the size of the nanoemulsion nanodroplets for food applications, analogous
      studies for nanoemulsions for therapeutic applications are limited. Here we
      present a study on the production of lipid-stabilised oil nanodroplets (LONDs)
      towards medical applications. A number of biocompatible oils were used to form
      LONDs with phospholipid coatings, and among these, squalane and tripropionin were
      chosen as model oils for subsequent studies. LONDs were formed by high pressure
      homogenisation, and their size was found to decrease with increasing production
      pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100
      and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were
      stable for over six weeks, at 4 degrees C, and also under physiological
      conditions, showing modest changes in size (<10%). The hydrophobic drug
      combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency
      of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR
      mouse endothelial cells treated with CA4 tripropionin LONDs showed the
      microtubule disruption, characteristic of drug uptake for all tested doses, which
      suggests successful release of the CA4 from the LONDs.

PMID- 28495583
TI  - Application of miscibility analysis and determination of Soluplus solubility map
      for development of carvedilol-loaded nanofibers.
AB  - Electrospinning was used to produce carvedilol-loaded Soluplus polymer nanofibers
      using a systematic approach. Miscibility between drug and polymer was determined
      through calculation of the interaction parameter, chi, and the difference between
      the total solubility parameters, Deltadt. A solubility map for Soluplus was
      obtained by examining different solvent systems, carrying out electrospinning,
      and characterizing the nanofibers formed. Miscibility studies showed that
      carvedilol and Soluplus can form a miscible system (chi=-2.3054;
      Deltadeltat<7.0MPa1/2). Based on the Soluplus solubility map, acetone: chloroform
      (90:10; w/w) represents a suitable solvent system for electrospinning of
      carvedilol-loaded Soluplus nanofibers. Scanning electron microscopy of these
      nanofiber samples showed smooth surface morphology. The nanofibers had a regular
      cylindrical morphology. Beads appeared along the nanofibers more frequently in
      formulations with lower percentages of carvedilol. Differential scanning
      calorimetry showed no melting endothermic peak for carvedilol, which suggests its
      complete conversion from the crystalline to the amorphous form (at polymer:
      carvedilol 1:1). The infrared spectrum of the carvedilol-loaded Soluplus
      nanofibers showed no characteristic carvedilol peak at 3344.5cm-1, which suggests
      interactions between carvedilol and Soluplus. Dissolution studies of these
      nanofibers showed improved pure carvedilol dissolution properties, with >85% of
      the carvedilol released in the first 15min, versus 20% for pure carvedilol. The
      use of miscibility analysis and polymer solubility studies demonstrate great
      technological potential to tackle the challenge for inadequate dissolution of
      poorly water-soluble drugs.

PMID- 28495584
TI  - Food effects in paediatric medicines development for products Co-administered
      with food.
AB  - A small amount of food is commonly used to aid administration of medicines to
      children to improve palatability and/or swallowability. However the impact of
      this co-administered food on the absorption and subsequent pharmacokinetic
      profile of the drug is unknown. Existing information on food effects is limited
      to standard protocols used to evaluate the impact of a high fat meal in an adult
      population using the adult medication. In the absence of a substantial body of
      data, there are no specific guidelines available during development of paediatric
      products relating to low volumes of potentially low calorie food. This paper
      brings together expertise to consider how the impact of co-administered food can
      be risk assessed during the development of a paediatric medicine. Two case
      studies were used to facilitate discussions and seek out commonalities in risk
      assessing paediatric products; these case studies used model drugs that differed
      in their solubility, a poorly soluble drug that demonstrated a positive food
      effect in adults and a highly soluble drug where a negative food effect was
      observed. For poorly soluble drugs risk assessments are centred upon
      understanding the impact of food on the in vivo solubility of the drug which
      requires knowledge of the composition of the food and the volumes present within
      the paediatric gastrointestinal tract. Further work is required to develop age
      appropriate in vitro and in silico models that are representative of paediatric
      populations. For soluble drugs it is more important to understand the mechanisms
      that may lead to a food effect, this may include interactions with transporters
      or the impact of the food composition on gastro-intestinal transit or even
      altered gastric motility. In silico models have the most promise for highly
      soluble drug products although it is essential that these models reflect the
      relevant mechanisms involved in potential food effects. The development of
      appropriate in vitro and in silico tools is limited by the lack of available
      clinical data that is critical to validate any tool. Further work is required to
      identify globally acceptable and available vehicles that should be the first
      option for co-administration with medicines to enable rapid and relevant risk
      assessment.

PMID- 28495585
TI  - Rapid separation of very low concentrations of bacteria from blood.
AB  - A rapid and accurate diagnosis of the species and antibiotic resistance of
      bacteria in septic blood is vital to increase survival rates of patients with
      bloodstream infections, particularly those with carbapenem-resistant
      enterobacteriaceae (CRE) infections. The extremely low levels in blood (1 to
      100CFU/ml) make rapid diagnosis difficult. In this study, very low concentrations
      of bacteria (6 to 200CFU/ml) were separated from 7ml of whole blood using rapid
      sedimentation in a spinning hollow disk that separated plasma from red and white
      cells, leaving most of the bacteria suspended in the plasma. Following less than
      a minute of spinning, the disk was slowed, the plasma was recovered, and the
      bacteria were isolated by vacuum filtration. The filters were grown on nutrient
      plates to determine the number of bacteria recovered from the blood. Experiments
      were done without red blood cell (RBC) lysis and with RBC lysis in the recovered
      plasma. While there was scatter in the data from blood with low bacterial
      concentrations, the mean average recovery was 69%. The gender of the blood donor
      made no statistical difference in bacterial recovery. These results show that
      this rapid technique recovers a significant amount of bacteria from blood
      containing clinically relevant low levels of bacteria, producing the bacteria in
      minutes. These bacteria could subsequently be identified by molecular techniques
      to quickly identify the infectious organism and its resistance profile, thus
      greatly reducing the time needed to correctly diagnose and treat a blood
      infection.

PMID- 28495586
TI  - Solid-phase synthesis of highly repetitive chromatin assembly templates.
AB  - DNA templates for assembling chromatin model systems typically consist of
      numerous repeats of nucleosome positioning sequences, making their synthesis
      challenging. Here we describe a solid-phase strategy for generating such
      templates using sequential enzymatic ligation of DNA monomers. Using single
      nucleosome site monomers, we can either generate a twelve-nucleosome site target,
      or systematically access intermediate-sized templates. Using twelve nucleosome
      positioning site monomers, longer templates can be generated. Our synthesized
      templates assemble into well-defined chromatin model systems, demonstrating the
      utility of our solid-phase approach. Moreover, our strategy should be more widely
      applicable to generating other DNAs containing highly repetitive DNA sequences.

PMID- 28495587
TI  - Dose-response analysis of epigenetic, metabolic, and apical endpoints after short
      term exposure to experimental hepatotoxicants.
AB  - Identification of sensitive and novel biomarkers or endpoints associated with
      toxicity and carcinogenesis is of a high priority. There is increasing interest
      in the incorporation of epigenetic and metabolic biomarkers to complement apical
      data; however, a number of questions, including the tissue specificity, dose
      response patterns, early detection of those endpoints, and the added value need
      to be addressed. In this study, we investigated the dose-response relationship
      between apical, epigenetic, and metabolomics endpoints following short-term
      exposure to experimental hepatotoxicants, clofibrate (CF) and phenobarbital (PB).
      Male F344 rats were exposed to PB (0, 5, 25, and 100 mg/kg/day) or CF (0, 10, 50,
      and 250 mg/kg/day) for seven days. Exposure to PB or CF resulted in dose
      dependent increases in relative liver weights, hepatocellular hypertrophy and
      proliferation, and increases in Cyp2b1 and Cyp4a1 transcripts. These changes were
      associated with altered histone modifications within the regulatory units of
      cytochrome genes, LINE-1 DNA hypomethylation, and altered microRNA profiles.
      Metabolomics data indicated alterations in the metabolism of bile acids. This
      study provides the first comprehensive analysis of the apical, epigenetic and
      metabolic alterations, and suggests that the latter two occur within or near the
      dose response curve of apical endpoint alterations following exposure to
      experimental hepatotoxicants.

PMID- 28495588
TI  - RIFM fragrance ingredient safety assessment, Isoamyl butyrate, CAS Registry
      Number 106-27-4.

PMID- 28495591
TI  - The HLA-DR mediated signalling increases the migration and invasion of melanoma
      cells, the expression and lipid raft recruitment of adhesion receptors, PD-L1 and
      signal transduction proteins.
AB  - The constitutive expression of Major Histocompatibility Complex (MHC) class II
      molecules is restricted to professional Antigen-Presenting Cells (APCs),
      nevertheless almost 50% of melanomas express constitutively the MHC class II
      molecules. Therefore, in two MHC class II constitutive expressing melanoma cell
      lines we studied the signalling mediated by the HLA-DR molecules in the aim to
      understand the consequence of class II mediated signalling on metastatic
      dissemination of melanoma. In particular, we reported that the HLA-DR mediated
      signalling play a new role in melanoma progression, increasing the migration and
      invasion of melanoma cells. Furthermore, we showed that the HLA-DR mediated
      signalling increases the expression and the lipid raft localisation of class II
      molecules, PD-L1 receptor, Integrin and CAM adhesion receptors, FAK, AKT and
      STAT3 signalling proteins. We also showed that the HLA-DR mediated signalling
      increases the activation of FAK, AKT, ERK, PKC and STAT3 signalling proteins and
      the expression of ILK, PAX, BRAF, ERK and PKC. Indeed, the results showed suggest
      that the HLA-DR mediated signalling provides a platform useful to frustrate an
      effective anti-tumour response and to increase melanoma migration and metastatic
      dissemination of this cancer.

PMID- 28495590
TI  - Concurrent activation of beta2-adrenergic receptor and blockage of GPR55 disrupts
      pro-oncogenic signaling in glioma cells.
AB  - Activation of beta2-adrenergic receptor (beta2AR) and deorphanized GPR55 has been
      shown to modulate cancer growth in diverse tumor types in vitro and in xenograft
      models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent
      compound that agonizes beta2AR but inhibits GPR55-mediated pro-oncogenic
      responses. Here, we investigated the molecular mechanisms underlying the anti
      tumorigenic effects of concurrent beta2AR activation and GPR55 blockade in C6
      glioma cells using (R,R')-MNF as a marker ligand. Our data show that (R,R')-MNF
      elicited G1-phase cell cycle arrest and apoptosis, reduced serum-inducible cell
      motility, promoted the phosphorylation of PKA target proteins, and inhibited
      constitutive activation of ERK and AKT in the low nanomolar range, whereas high
      nanomolar levels of (R,R')-MNF were required to block GPR55-mediated cell
      motility. siRNA knockdown and pharmacological inhibition of beta2AR activity were
      accompanied by significant upregulation of AKT and ERK phosphorylation, and
      selective alteration in (R,R')-MNF responsiveness. The effects of agonist
      stimulation of GPR55 on various readouts, including cell motility assays, were
      suppressed by (R,R')-MNF. Lastly, a significant increase in phosphorylation
      mediated inactivation of beta-catenin occurred with (R,R')-MNF, and we provided
      new evidence of (R,R')-MNF-mediated inhibition of oncogenic beta-catenin
      signaling in a C6 xenograft tumor model. Thus, simultaneous activation of beta2AR
      and blockade of GPR55 may represent a novel therapeutic approach to combat the
      progression of glioblastoma cancer.

PMID- 28495589
TI  - Reduced FAK-STAT3 signaling contributes to ER stress-induced mitochondrial
      dysfunction and death in endothelial cells.
AB  - Excessive endoplasmic reticulum (ER) stress leads to cell loss in many diseases,
      e.g., contributing to endothelial cell loss after spinal cord injury. Here, we
      determined whether ER stress-induced mitochondrial dysfunction could be explained
      by interruption of the focal adhesion kinase (FAK)-mitochondrial STAT3 pathway we
      recently discovered. ER stress was induced in brain-derived mouse bEnd5
      endothelial cells by thapsigargin or tunicamycin and caused apoptotic cell death
      over a 72h period. In concert, ER stress caused mitochondrial dysfunction as
      shown by reduced bioenergetic function, loss of mitochondrial membrane potential
      and increased mitophagy. ER stress caused a reduction in mitochondrial
      phosphorylated S727-STAT3, known to be important for maintaining mitochondrial
      function. Normal activation or phosphorylation of the upstream cytoplasmic FAK
      was also reduced, through mechanisms that involve tyrosine phosphatases and
      calcium signaling, as shown by pharmacological inhibitors, bisperoxovanadium
      (bpV) and 2-aminoethoxydiphenylborane (APB), respectively. APB mitigated the
      reduction in FAK and STAT3 phosphorylation, and improved endothelial cell
      survival caused by ER stress. Transfection of cells rendered null for STAT3 using
      CRISPR technology with STAT3 mutants confirmed the specific involvement of S727
      STAT3 inhibition in ER stress-mediated cell loss. These data suggest that loss of
      FAK signaling during ER stress causes mitochondrial dysfunction by reducing the
      protective effects of mitochondrial STAT3, leading to endothelial cell death. We
      propose that stimulation of the FAK-STAT3 pathway is a novel therapeutic approach
      against pathological ER stress.

PMID- 28495592
TI  - miR-21 Promotes Fibrogenesis in Peritoneal Dialysis.
AB  - Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for
      those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal
      cavity and help define peritoneal response to treatment-associated injury, a
      major reason for treatment failure. miRNAs are important regulators, but their
      roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one
      of the most abundant miRNAs in primary MCs, and was up-regulated by the
      profibrotic cytokine transforming growth factor-beta1 and in PD effluent-derived
      MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in
      peritoneal membrane biopsy specimens from PD patients compared to healthy
      controls (PD biocompatible, 5.86*, P = 0.0001; PD conventional, 7.09*, P <
      0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21
      was higher in those receiving the therapy long-term compared to new starters (n =
      230, miR-21 3.26*, P = 0.001) and associated with icodextrin use (R = 0.52; 95%
      CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate
      cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell
      death 4 protein was decreased in peritoneal membrane biopsy specimens from PD
      patients compared to healthy controls. New miR-21 targets were identified that
      may be important during PD fibrogenesis. These data identify miR-21 as an
      important effector of fibrosis in the peritoneal membrane, and a promising
      biomarker in the dialysis effluent for membrane change in patients receiving PD.

PMID- 28495593
TI  - Enhanced air dispersion modelling at a typical Chinese nuclear power plant site:
      Coupling RIMPUFF with two advanced diagnostic wind models.
AB  - An enhanced air dispersion modelling scheme is proposed to cope with the building
      layout and complex terrain of a typical Chinese nuclear power plant (NPP) site.
      In this modelling, the California Meteorological Model (CALMET) and the
      Stationary Wind Fit and Turbulence (SWIFT) are coupled with the Riso Mesoscale
      PUFF model (RIMPUFF) for refined wind field calculation. The near-field diffusion
      coefficient correction scheme of the Atmospheric Relative Concentrations in the
      Building Wakes Computer Code (ARCON96) is adopted to characterize dispersion in
      building arrays. The proposed method is evaluated by a wind tunnel experiment
      that replicates the typical Chinese NPP site. For both wind speed/direction and
      air concentration, the enhanced modelling predictions agree well with the
      observations. The fraction of the predictions within a factor of 2 and 5 of
      observations exceeds 55% and 82% respectively in the building area and the
      complex terrain area. This demonstrates the feasibility of the new enhanced
      modelling for typical Chinese NPP sites.

PMID- 28495595
TI  - Low plasma leptin level at admission predicts delirium in critically ill
      patients: A prospective cohort study.
AB  - The pathophysiology of delirium remains poorly understood. Low leptin level has
      been associated with features leading to delirium such as dysregulated immune
      functions and loss of neuroprotective effects. The purpose of the present study
      was to investigate the relationship between plasma leptin level at intensive care
      unit (ICU) entry and subsequent occurrence of delirium in critically ill
      patients. This single-center prospective cohort study in China allocated 336
      critically ill patients admitted to ICU between 05/2015 and 05/2016 into a
      delirium group (n=102) and non-delirium group (n=234) based on whether delirium
      occurred during their stay at the ICU. Patients were examined at least twice
      daily and delirium was diagnosed using the Confusion Assessment Method for the
      ICU (CAM-ICU). Blood samples were obtained after ICU entry. Plasma leptin
      concentrations were measured by ELISA. Delirium occurred in 30.4% (102/336) of
      patients. Patients who developed delirium showed significantly lower leptin level
      at ICU entry than those who did not (6.1+/-3.2 vs. 9.2+/-5.9ng/mL; P<0.001). Low
      plasma leptin level at ICU entry was independently associated with subsequent
      occurrence of delirium (OR, 0.865; 95%CI, 0.802-0.934; P<0.001). Other
      independent risk factors for delirium included increasing age (OR, 1.050; 95%CI,
      1.020-1.080; P=0.001) and Acute Physiology and Chronic Health Evaluation-II
      (APACHE-II) score (OR, 1.148; 95%CI, 1.092-1.208; P<0.001). Patients who
      developed delirium had a prolonged duration of ICU stay and higher mortality. Low
      plasma leptin level at ICU entry was associated with the occurrence of delirium
      in critically ill patients.

PMID- 28495594
TI  - Elevated MUs-ms timescale backbone dynamics in the transition state analog form
      of arginine kinase.
AB  - Arginine kinase catalyzes reversible phosphoryl transfer between arginine and
      ATP. Crystal structures of arginine kinase in an open, substrate-free form and
      closed, transition state analog (TSA) complex indicate that the enzyme undergoes
      substantial domain and loop rearrangements required for substrate binding,
      catalysis, and product release. Nuclear magnetic resonance (NMR) has shown that
      substrate-free arginine kinase is rigid on the ps-ns timescale (average S2=0.84+/
      0.08) yet quite dynamic on the us-ms timescale (35 residues with Rex, 12%), and
      that movements of the N-terminal domain and the loop comprising residues I182
      G209 are rate-limiting on catalysis. Here, NMR of the TSA-bound enzyme shows
      similar rigidity on the ps-ns timescale (average S2=0.91+/-0.05) and
      substantially increased MUs-ms timescale dynamics (77 residues; 22%). Many of the
      residues displaying MUs-ms dynamics in NMR Carr-Purcell-Meiboom-Gill (CPMG) 15N
      backbone relaxation dispersion experiments of the TSA complex are also dynamic in
      substrate-free enzyme. However, the presence of additional dynamic residues in
      the TSA-bound form suggests that dynamics extend through much of the C-terminal
      domain, which indicates that in the closed form, a larger fraction of the protein
      takes part in conformational transitions to the excited state(s). Conformational
      exchange rate constants (kex) of the TSA complex are all approximately 2500s-1,
      higher than any observed in the substrate-free enzyme (800-1900s-1). Elevated MUs
      ms timescale protein dynamics in the TSA-bound enzyme is more consistent with
      recently postulated catalytic networks involving multiple interconnected states
      at each step of the reaction, rather than a classical single stabilized
      transition state.

PMID- 28495596
TI  - The role of Omega-3 and Omega-9 fatty acids for the treatment of neuropathic pain
      after neurotrauma.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA)
      and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental
      models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms
      of PUFAs include reduced neuroinflammation and oxidative stress, enhanced
      neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9
      monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2
      OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces
      noxious hyperreflexia and pain-related anxiety behavior following peripheral
      nerve injury and improves sensorimotor function following spinal cord injury
      (SCI), including facilitation of descending inhibitory antinociception. The
      relative safe profile of neuroactive fatty acids (FAs) holds promise for the
      future clinical development of these molecules as analgesic agents. This article
      is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting
      Biomembranes edited by Pablo V. Escriba.

PMID- 28495597
TI  - The learned reinterpretation of fluency in amnesia.
AB  - Fluency is one of many cues that are involved in memory decisions. To date,
      however, the extent to which fluency-based decisions are preserved in amnesia is
      not yet clear. In this study, we tested and found differences in how patients
      with amnesia (n=8) and control participants (n=16) use fluency when making
      recognition decisions (Experiment 1). Our results suggested that these
      differences could be due to changes in the readiness with which patients
      attribute the subjective feeling of fluency to pre-exposure when an alternative
      explanation is available (i.e., the perceptual quality of the item). Secondly, we
      explored the hypothesis that changes in attribution processes in patients with
      amnesia are explained by a decrease in contingency between processing fluency and
      previous occurrence of stimuli in patients' daily lives, leading them to consider
      that fluency is not a relevant cue for memory (Experiment 2). Specifically, 42
      healthy participants were put either in a condition where the positive
      contingency between fluent processing and previous encounters with an item was
      systematically confirmed (classic condition) or in a condition where the
      classical association between fluency and prior exposure was systematically
      reversed (reversed condition). Results indicated that participants more readily
      attribute fluency to the alternative external source than to past experience in
      the reversed condition than in the classic condition, mimicking the pattern of
      results shown by participants with amnesia in Experiment 1. Implications of these
      findings are discussed.

PMID- 28495598
TI  - Mental arithmetic in the bilingual brain: Language matters.
AB  - How do bilinguals solve arithmetic problems in each of their languages? We
      investigated this question by exploring the neural substrates of mental
      arithmetic in bilinguals. Critically, our population was composed of a
      homogeneous group of adults who were fluent in both of their instruction
      languages (i.e., German as first instruction language and French as second
      instruction language). Twenty bilinguals were scanned with fMRI (3T) while
      performing mental arithmetic. Both simple and complex problems were presented to
      disentangle memory retrieval occuring in very simple problems from arithmetic
      computation occuring in more complex problems. In simple additions, the left
      temporal regions were more activated in German than in French, whereas no brain
      regions showed additional activity in the reverse constrast. Complex additions
      revealed the reverse pattern, since the activations of regions for French
      surpassed the same computations in German and the extra regions were located
      predominantly in occipital regions. Our results thus highlight that highly
      proficient bilinguals rely on differential activation patterns to solve simple
      and complex additions in each of their languages, suggesting different solving
      procedures. The present study confirms the critical role of language in
      arithmetic problem solving and provides novel insights into how highly proficient
      bilinguals solve arithmetic problems.

PMID- 28495599
TI  - Effects of the Brain-Derived Neurotrophic Factor Val66Met polymorphism and
      resting brain functional connectivity on individual differences in tactile
      cognitive performance in healthy young adults.
AB  - Cognitive processes involve input from multiple sensory modalities and obvious
      differences in the level of cognitive function can be observed between
      individuals. Evidence to date understanding the biological basis of tactile
      cognitive variability, however, is limited compared with other forms of sensory
      cognition. Data from auditory and visual cognition research suggest that
      variations in both genetics and intrinsic brain function might contribute to
      individual differences in tactile cognitive performance. In the present study, by
      using the tactual performance test (TPT), a widely used neuropsychological
      assessment tool, we investigated the effects of the brain-derived neurotrophic
      factor (BDNF) Val66Met polymorphism and resting-state brain functional
      connectivity (FC) on interindividual variability in TPT performance in healthy,
      young Chinese adults. Our results showed that the BDNF genotypes and resting
      state FC had significant effects on the variability in TPT performance, together
      accounting for 32.5% and 19.1% of the variance on TPT total score and Memory
      subitem score respectively. Having fewer Met alleles, stronger anticorrelations
      between left posterior superior temporal gyrus and somatosensory areas (right
      postcentral gyrus and right parietal operculum cortex), and greater positive
      correlation between left parietal operculum cortex and left central opercular
      cortex, all correspond with better performance of TPT task. And FC between left
      parietal operculum cortex and left central opercular cortex might be a mediator
      of the relationship between BDNF genotypes and Memory subitem score. These data
      demonstrate a novel contribution of intrinsic brain function to tactile cognitive
      capacity, and further confirm the genetic basis of tactile cognition. Our
      findings might also explain the interindividual differences in cognitive ability
      observed in those who are blind and/or deaf from a new perspective.

PMID- 28495600
TI  - The effect of cortical and subcortical lesions on spontaneous expression of
      memory-encoded and emotionally infused information: Evidence for a role of the
      ventral stream.
AB  - The ventral stream of language processing has been implicated in the spontaneous
      expression of memory-encoded and emotionally infused information. The present
      study investigated whether left hemispheric lesions in post-stroke right-handed
      aphasic patients may be selectively associated with specific language functions.
      Speech rate was assessed with two tasks, one based on autobiographical memory of
      an emotionally infused event (stroke story narration) and the other based on
      information that is visually available at the time of speech generation ("cookie
      theft" picture description). CT and/or MRI scans were obtained for each patient
      and lesions located in 16 regions of the left hemisphere were identified and
      coded. The total number of cortical and subcortical areas affected served as a
      measure of lesion extent. While mean speech rates were similar across conditions,
      there were different patterns of association between each index and specific
      lesion sites. Non-parametric quantile regression statistical models constructed
      to assess dependence of both speech rate indices on each lesion locus indicated
      that the speech rate in the stroke story had significant inverse associations
      with total number of lesioned areas, as well as lesions in the inferior frontal
      gyrus and the external/extreme capsule region. The cookie theft speech rate had
      significant inverse associations with total number of lesioned areas as well as
      lesion in the inferior frontal gyrus, but not with the external/extreme capsule
      region. In sum, integrity of the extreme/external capsule region appears to be
      important selectively for the Stroke Story task, supporting the hypothesis that
      the ventral stream plays a central role in spontaneous expression of memory
      encoded and emotionally infused information.

PMID- 28495601
TI  - Structural connectivity subserving verbal fluency revealed by lesion-behavior
      mapping in stroke patients.
AB  - Tests of verbal fluency have been widely used to assess the cognitive functioning
      of persons, and are typically classified into two categories (semantic and
      phonological fluency). While widely-distributed divergent and convergent brain
      regions have been found to be involved in semantic and phonological fluency, the
      anatomical connectivity underlying the fluency is not well understood. The
      present study aims to construct a comprehensive white-matter network associated
      with semantic and phonological fluency by investigating the relationship between
      the integrity of 22 major tracts in the whole brain and semantic fluency
      (measured by 3 cues) and phonological fluency (measured by 2 cues) in a group of
      51 stroke patients. We found five left-lateralized tracts including the anterior
      thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), uncinate
      fasciculus (UF), superior longitudinal fasciculus (SLF) and frontal aslant tract
      (FAT) were significantly correlated with the scores of both semantic and
      phonological fluencies. These effects persisted even when we ruled out the
      influence of potential confounding factors (e.g., total lesion volume). Moreover,
      the damage to the first three tracts caused additional impairments in the
      semantic compared to the phonological fluency. These findings reveal the white
      matter neuroanatomical connectivity underlying semantic and phonological fluency,
      and deepen the understanding of the neural network of verbal fluency.

PMID- 28495602
TI  - A review of traditional uses, phytochemistry and pharmacology of Portulaca
      oleracea L.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Portulaca oleracea L. is a widespread medicinal
      plant that is used not only as an edible plant, but also as a traditional
      medicine for alleviating a wide spectrum of diseases. It is a well-known plant in
      the European Traditional Medicine. PA is mentioned by Dioscorides (40-90 CE),
      with the name of "andrachne". AIM OF THE REVIEW: In this study, we provide
      detailed information on botany, traditional uses, phytochemistry, pharmacological
      uses, pharmacokinetics and safety of P. oleracea. MATERIALS AND METHODS: An
      extensive search on electronic databases including PubMed, Web of Science, Google
      Scholar, ScienceDirect, Scopus, conference papers, local herbal encyclopedias,
      articles, books (in English, French, Arabic, Persian, etc.) and also a number of
      unpublished handwritten manuscripts was done to find articles have been published
      between 1956 and 2015 on pharmacology and phytochemistry of P. oleracea. RESULTS:
      P. oleracea has been addressed in De Materia Medica as an astringent, and a
      remedy for headaches, inflammation of the eyes and other organs, burning of the
      stomach, erysipela, disorders of the bladder, numbness of the teeth, excessive
      sexual desire, burning fevers, worms, dysentery, hemorrhoids, eruptions of blood,
      and bites. Phytochemical investigations revealed that this plant a wide range of
      secondary metabolites including alkaloids, terpenoids, flavonoids and organic
      acids. The most important pharmacological activities are renoprotective
      activities and effects on metabolism. P. oleracea could successfully decrease
      blood glucose and lipid profile of patients with metabolic syndrome. The safety
      of P. oleracea has been reported in many clinical trials. CONCLUSION: Modern
      pharmacological studies have now proven many traditional uses of P. oleracea,
      including anti-hyperglycemic and anti-hyperlipidemic, renoprotective and
      hepatoprotective effects. In addition, in many clinical trials P. oleracea showed
      no adverse effects and constipation was reported as the most frequent adverse
      effect.

PMID- 28495603
TI  - Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic
      applications of Clinacanthus nutans (Burm. f.) Lindau: A comprehensive review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Clinacanthus nutans (Burm. f.) Lindau, a widely
      used medicinal plant, is extensively grown in tropical Asia and Southeast Asian
      countries. C. nutans, with its broad spectrum of pharmacological activities, has
      been traditionally used to treat cancer, inflammatory disorders, diabetes, insect
      bites, and skin problems, consumed as a vegetable, mixed with fresh juices, in
      concoctions, and as a whole plant. The present review analyzes the advances in
      the ethnopharmacology, phytochemistry, pharmacology, and toxicology of C. nutans.
      In addition, the needs and perspectives for future investigation of this plant
      are addressed. AIM OF THE REVIEW: This review aims to provide a comprehensive
      report on the ethnomedicinal use, phytochemistry, pharmacological activities,
      molecular mechanisms, and nutritional values of C. nutans. The present review
      will open new avenues for further in-depth pharmacological studies of C. nutans
      for it to be developed as a potential nutraceutical and to improve the available
      products in the market. MATERIAL AND METHODS: All the available information on C.
      nutans was collected using the key words "Clinacanthus nutans" and/or
      "ethnomedicine" and/or "phytochemicals" and/or "anticancer" and/or "anti
      inflammatory" and/or "antiviral" through an electronic search of the following
      databases: PubMed, Web of Science, EMBASE, Cochrane Library, Clinical Trials.org,
      SciFinder Scholar, Scopus, and Google Scholar. In addition, unpublished
      materials, Ph.D. and M.Sc. dissertations, conference papers, and ethnobotanical
      textbooks were used. The Plant List (www.theplantlist.org) and International
      Plant Name Index databases were used to validate the scientific name of the
      plant. RESULTS: The literature supported the ethnomedicinal uses of C. nutans as
      recorded in Thailand, Indonesia, and Malaysia for various purposes. Bioactivities
      experimentally proven for C. nutans include cytotoxic, anticancer, antiviral,
      anti-inflammatory, immunomodulatory, antidiabetic, antioxidant,
      antihyperlipidemic, antimicrobial, and chemotherapeutic (in aquaculture)
      activities. Most of these activities have so far only been investigated in
      chemical, cell-based, and animal assays. Various groups of phytochemicals
      including five sulfur-containing glycosides, eight chlorophyll derivatives, nine
      cerebrosides, and a monoacylmonogalactosyl glycerol are present in C. nutans. The
      presence of two glycerolipids, four sulfur-containing compounds, six known
      flavones, a flavanol, four flavonols, two phytosterols, one polypeptide, and
      various phenolics and fatty acids largely influences its diverse bioactivities.
      Numerous reports justify the ethnomedicinal use of C. nutans as an antiviral
      agent in treating herpes simplex virus and varicella-zoster virus infections and
      as part of a traditional anticancer anti-inflammatory concoction agent for
      various inflammatory diseases. C. nutans tea was reported to have a good
      percentage of carbohydrate, crude protein, minerals, essential amino acids,
      nonessential amino acids, and essential fatty acids. Acute, subacute, and
      subchronic toxicity studies demonstrated that oral administration of ethanol and
      methanol extracts of C. nutans to male Swiss albino mice and male Sprague-Dawley
      (SD) rats, respectively, did not lead to any toxicity or adverse effects on the
      animal behavior and organs when used in amounts as high as 2g/kg. CONCLUSION: The
      collected literatures demonstrated that, as an important traditional medicine, C.
      nutans is a promising ethnomedicinal plant with various extracts and bioactive
      compounds exhibiting multifarious bioactivities. However, it is important for
      future studies to conduct further in vitro and in vivo bioactivity evaluations
      systematically, following the standard pharmacology guidelines. It is crucial to
      elucidate in-depth molecular mechanisms, structure-activity relationships, and
      potential synergistic and antagonistic effects of multi-component extracts and
      bioactive constituents derived from C. nutans. Further studies should also focus
      on comprehensive toxicity that includes long-term effects and adverse effects on
      target organs of C. nutans and bioactive compounds in correlation with the
      specific pharmacological effects.

PMID- 28495604
TI  - Conditioning with spatio-temporal patterns: Constraining the contribution of the
      hippocampus to configural learning.
AB  - The conditions under which the hippocampus contributes to learning about spatio
      temporal configural patterns are not fully established. The aim of Experiments 1
      4 was to investigate the impact of hippocampal lesions on learning about where or
      when a reinforcer would be delivered. In each experiment, the rats received
      exposure to an identical set of patterns (i.e., spotted+morning, checked+morning,
      spotted+afternoon and checked+afternoon); and the contexts (Experiment 1), times
      of day (Experiment 2), or their configuration (Experiments 3 and 4) signalled
      whether or not a reinforcer would be delivered. The fact that hippocampal damage
      did not disrupt the formation of simple or configural associations involving
      spatio-temporal patterns is surprising, and suggests that the contribution of the
      hippocampus is restricted to mediated learning (or updating) involving spatio
      temporal configurations.

PMID- 28495605
TI  - Inactivation of basolateral amygdala prevents chronic immobilization stress
      induced memory impairment and associated changes in corticosterone levels.
AB  - Chronic stress causes detrimental effects on various forms of learning and
      memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating
      certain forms of memory, but also in the modulation of the effects of stress.
      Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is
      believed to be one of the underlying causes for stress' effects on learning.
      Thus, it is plausible that preventing the effects of CIS on amygdala would
      preclude its deleterious cognitive effects. Accordingly, in the first part, we
      evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced
      hippocampal-dependent spatial learning using a partially baited radial arm maze
      task. The BLA was ablated bilaterally using ibotenic acid prior to CIS.
      Chronically stressed rats showed impairment in spatial learning with decreased
      percentage correct choice and increased reference memory errors. Excitotoxic
      lesion of the BLA prevented the impairment in spatial learning and reference
      memory. In the retention test, lesion of the BLA was able to rescue the chronic
      stress-induced impairment. Interestingly, stress-induced enhanced plasma
      corticosterone levels were partially prevented by the lesion of BLA. These
      results motivated us to evaluate if the same effects can be observed with
      temporary inactivation of BLA, only during stress. We found that chronic stress
      induced spatial learning deficits were also prevented by temporary inactivation
      of the BLA. Additionally, temporary inactivation of BLA partially precluded the
      stress-induced increase in plasma corticosterone levels. Thus, inactivation of
      BLA precludes stress-induced spatial learning deficits, and enhanced plasma
      corticosterone levels. It is speculated that BLA inactivation-induced reduction
      in corticosterone levels during stress, might be crucial in restoring spatial
      learning impairments. Our study provides evidence that amygdalar modulation
      during stress might be beneficial for strategic management of stress-related
      cognitive deficits.

PMID- 28495606
TI  - The synthetic cannabinoid WIN-55,212 induced-apoptosis in cytotrophoblasts cells
      by a mechanism dependent on CB1 receptor.
AB  - The endocannabinoid system has evolved as a key regulator in several pathological
      and physiological processes, including placentation, decidualization and
      implantation. In addition, it is known that Cannabis and cannabinoids negatively
      affect female reproduction. Although, the biological action of synthetic
      cannabinoids, such as WIN-55,212, in human fertility and pregnancy outcome remain
      to be unveiled. A tight balance between proliferation, differentiation and
      apoptosis of trophoblast cells is required for placental development and
      pregnancy outcome. Therefore, in this work, the effects of the synthetic
      cannabinoid WIN-55,212 in placental cytotrophoblast cells were explored. For
      that, it was used a human choriocarcinoma cell line, BeWo cells, and primary
      cultures of human cytotrophoblasts isolated from term placentas. Results
      demonstrate that this synthetic cannabinoid induces cell cycle arrest. We also
      observed that cell viability loss was associated with a disruption of
      mitochondrial membrane potential and activation of caspases -9 and -3/-7
      independently of reactive oxygen species (ROS) production or recruitment of the
      endoplasmic reticulum stress marker CHOP. Moreover, these effects were prevented
      by pre-incubation with a selective cannabinoid receptor 1 (CBR1) antagonist
      (AM281). Thus, our results provide strong evidences of the apoptotic process
      induced by WIN-55,212 through the activation of the CBR1, which may reveal the
      impact of cannabinoids consumption during placental development.

PMID- 28495607
TI  - Prenatal exposure to lambda-cyhalothrin alters brain dopaminergic signaling in
      developing rats.
AB  - The present study is focused to decipher the molecular mechanisms associated with
      dopaminergic alterations in corpus striatum of developing rats exposed prenatally
      to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There
      was no significant change in the mRNA and protein expression of DA-D1 receptors
      at any of the doses of LCT (0.5, 1 and 3mg/kg body weight) in corpus striatum of
      developing rats exposed prenatally to LCT on PD22 and PD45. Prenatal exposure to
      LCT (1 and 3mg/kg body weight) resulted to decrease the levels of mRNA and
      protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as
      compared to controls. Decrease in the binding of 3H-Spiperone in corpus striatum,
      known to label DA-D2 receptors was also distinct in developing rats on PD22.
      These rats also exhibited decrease in the expression of proteins - TH, DAT and
      VMAT2 involved in pre-dopaminergic signaling. Further, decrease in the expression
      of DARPP-32 and pCREB associated with increased expression of PP1alpha was
      evident in developing rats on PD22 as compared to controls. Interestingly, a
      trend of recovery in the expression of these proteins was observed in developing
      rats exposed to LCT at moderate dose (1.0mg/kg body weight) while alteration in
      the expression of these proteins continued to persist in those exposed at high
      dose (3.0mg/kg body weight) on PD45 as compared to respective controls. No
      significant change in the expression of any of these proteins was observed in
      corpus striatum of developing rats prenatally exposed to LCT at low dose
      (0.5mg/kg body weight) on PD22 and PD45 as compared to respective controls. The
      results provide interesting evidence that alterations in dopaminergic signaling
      on LCT exposure are due to selective changes in DA-D2 receptors in corpus
      striatum of developing rats. Further, these changes could be attributed to
      impairment in spontaneous motor activity on LCT exposure in developing rats.

PMID- 28495608
TI  - Short-term caloric restriction exerts neuroprotective effects following mild
      traumatic brain injury by promoting autophagy and inhibiting astrocyte
      activation.
AB  - Cognitive deficits may occur after mild traumatic brain injury (mTBI), but
      effective treatment modalities are presently unavailable. Caloric restriction
      (CR) has beneficial effects on neurodegenerative diseases and brain injury.
      However, the underlying mechanisms have not yet been clearly defined. Therefore,
      the aim of the present study was to investigate the short-term effects of CR
      treatment on cognitive function in mice after mTBI. Forty-five 12-week-old
      C57/BL6 mice were subjected to closed-head mTBI using a weight drop device. The
      mice were then randomly divided into three groups according to their diet for 30
      days: the normal calorie group (mTBI+NC group, n=15), the caloric restriction
      group (mTBI+CR group, n=15), and the high energy group (mTBI+HE group, n=15).
      After 30 days, the Morris water maze test was performed to evaluate learning
      abilities. Nissl staining, immunohistochemistry, and western blotting were used
      to monitor pathological changes and changes in autophagy-associated proteins in
      the hippocampus. The average escape latency was significantly shorter in the
      mTBI+CR group than in the mTBI+NC and mTBI+HE groups, and the number of target
      platform crossings in the mTBI+CR group was significantly higher than in the
      other two groups. In the hippocampus, the expression of GFAP and mTOR was
      increased in the mTBI+HE group and decreased in the mTBI+CR group. Conversely,
      the expression of LC3B was decreased in the mTBI+HE group and increased in the
      mTBI+CR group. Our findings suggest that short-term CR after mTBI may ameliorate
      cognitive dysfunction induced by mTBI by increasing the level of autophagy and
      suppressing astrocyte activation.

PMID- 28495609
TI  - Acute low-level alcohol consumption reduces phase locking of event-related
      oscillations in rodents.
AB  - Event-related oscillations (EROs) are rhythmic changes that are evoked by a
      sensory and/or cognitive stimulus that can influence the dynamics of the EEG.
      EROs are defined by the decomposition of the EEG signal into magnitude (energy)
      and phase information and can be elicited in both humans and animals. EROs have
      been linked to several relevant genes associated with ethanol dependence
      phenotypes in humans and are altered in selectively bred alcohol-preferring rats.
      However, pharmacological studies are only beginning to emerge investigating the
      impact low intoxicating doses of ethanol can have on event-related neural
      oscillations. The main goal of this study was to investigate the effects of low
      levels of voluntary consumption of ethanol, in rats, on phase locking of EROs in
      order to give further insight into the acute intoxicating effects of ethanol on
      the brain. To this end, we allow rats to self-administer unsweetened 20% ethanol
      over 15 intermittent sessions. This method results in a stable low-dose
      consumption of ethanol. Using an auditory event-related potential "oddball"
      paradigm, we investigated the effects of alcohol on the phase variability of EROs
      from electrodes implanted into the frontal cortex, dorsal hippocampus, and
      amygdala. We found that intermittent ethanol self-administration was sufficient
      to produce a significant reduction in overall intraregional synchrony across all
      targeted regions. These data suggest that phase locking of EROs within brain
      regions known to be impacted by alcohol may represent a sensitive biomarker of
      low levels of alcohol intoxication.

PMID- 28495610
TI  - "Allergic mood" - Depressive and anxiety symptoms in patients with seasonal
      allergic rhinitis (SAR) and their association to inflammatory, endocrine, and
      allergic markers.
AB  - A growing number of studies show an association between seasonal allergic
      rhinitis (SAR) with depression and anxiety. The underlying mechanisms of a link
      between SAR and affect, however, are still unclear. The objective of the present
      study was to investigate depressive symptoms and anxiety in SAR patients and
      their association to inflammatory and endocrine parameters. SAR patients (n=41)
      and non-allergic, healthy controls (n=42) were assessed during (pollen season)
      and out of symptomatic periods (non-pollen season). Inflammatory cytokine profile
      (Interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, IL-17, IFN-gamma, TNF-alpha),
      Immunoglobulin-E (IgE), hair cortisol concentrations (HCC), as well as sleep
      quality were measured. The present data show that during acute allergic
      inflammation SAR patients experienced a significant increase in Beck Depression
      Inventory (BDI-) II scores when (a) compared to the asymptomatic period and (b)
      when compared to the non-allergic controls, while no differences in anxiety were
      observed. Increased BDI-II scores in SAR patients were significantly associated
      with levels of IL-6 as well as IL-6/IL-10 and IFN-gamma/IL-10 ratios and further,
      to an early age at manifestation of SAR and poor sleep quality. These findings
      support a close relationship between acute allergic processes and affective
      states, with inflammatory cytokines, sleep, and age of manifestation as
      potentially relevant mediators.

PMID- 28495612
TI  - Effect of infrared light on live blood cells: Role of beta-carotene.
AB  - We have utilized Raman tweezers to measure and assign micro-Raman spectra of
      optically trapped, live red blood cells (RBCs), white blood cells (WBCs) and
      platelets. Various types of WBCs- both granulocytes, lymphocytes, and their
      different types have been studied. The Raman bands are assigned to different
      biomolecules of blood cells. The Raman spectra thus obtained has been enabled
      detection of beta-carotene in these blood cells, the spectral features of which
      act as a signature that facilitates experimental probing of the effect of 785nm
      laser light on different blood cells as a function of incident laser power in the
      mW range. The spectral changes that we obtain upon laser irradiation indicate
      that, both haemoglobin as well as the cell membrane sustains damage. In case of
      lymphocytes and platelets the peaks corresponding to beta-carotene showed drastic
      changes. Thorough analysis of the spectral changes indicates possibility of free
      radical induced damage of beta-carotene in lymphocytes and platelets. Among
      different blood cells, RBCs have a power threshold of only 10mW. The power
      threshold for other types of blood cells is somewhat higher, but always below
      about 30mW. These values are likely to serve as useful guides for Raman tweezers
      based experiments on live cells.

PMID- 28495611
TI  - HIV-1 TAT protein enhances sensitization to methamphetamine by affecting
      dopaminergic function.
AB  - Methamphetamine abuse is common among humans with immunodeficiency virus (HIV).
      The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic
      systems which may result in impaired reward processes and contribute to
      methamphetamine abuse. These studies investigated the impact of TAT expression on
      methamphetamine-induced locomotor sensitization, underlying changes in dopamine
      function and adenosine receptors in mesolimbic brain areas and neuroinflammation
      (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression
      in the brain were tested for locomotor activity in response to repeated
      methamphetamine injections and methamphetamine challenge after a 7-day abstinence
      period. Dopamine function in the nucleus accumbens (Acb) was determined using
      high performance liquid chromatography. Expression of dopamine and/or adenosine A
      receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR
      and immunohistochemistry analyses. Microarrays with pathway analyses assessed
      dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter
      switching of a reserve pool of non-dopaminergic neurons to a dopaminergic
      phenotype in the ventral tegmental area (VTA) was determined by
      immunohistochemistry and quantified with stereology. TAT expression enhanced
      methamphetamine-induced sensitization. TAT expression alone decreased striatal
      dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing
      ADORA2A receptors expression. Moreover, TAT expression combined with
      methamphetamine exposure was associated with increased adenosine A receptors
      (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA.
      TAT expression and methamphetamine exposure induced microglia activation with the
      largest effect after combined exposure. Our findings suggest that dopamine
      adenosine receptor interactions and reserve pool neuronal recruitment may
      represent potential targets to develop new treatments for methamphetamine abuse
      in individuals with HIV.

PMID- 28495613
TI  - Mode of action and human relevance of THF-induced mouse liver tumors.
AB  - In a National Toxicology Program (NTP) bioassay, inhalation of tetrahydrofuran
      (THF) induced liver tumors in female B6C3F1 mice but not in male mice or rats of
      either sex. Since THF is not genotoxic, the NTP concluded this carcinogenic
      activity was likely mediated via non-genotoxic modes of action (MOA). Based on
      evidence that THF and phenobarbital share a similar MOA, female Car/Pxr knock-out
      mice were orally exposed to THF to evaluate the potential role of CAR activation
      in the MOA for THF-induced liver tumors. Because data from this oral study with
      Car/Pxr knock-out mice (C57Bl/6) and the inhalation studies with wild type mice
      (B6C3F1) reported by NTP and others were derived from different strains, oral
      studies with wild type B6C3F1 and C57Bl/6 mice were conducted to ensure THF
      responses in both strains were comparable. As seen in inhalation studies with
      THF, oral exposure of wild type female mice to a maximum tolerated dose of THF
      increased total P450 content, CAR-related P450 activities, and hepatocyte
      proliferation; these effects were not observed in Car/Pxr knock-out female mice.
      This finding supports the hypothesis THF-induced carcinogenicity is likely
      mediated via CAR activation that has limited, if any, relevance to humans.

PMID- 28495614
TI  - Protective potential of different compounds and their combinations with MESNA
      against sulfur mustard-induced cytotoxicity and genotoxicity.
AB  - The purpose of this study was to evaluate the efficacy of potential candidate
      molecules or their combinations against strong alkylation agent sulfur mustard
      (SM) on the human lung alveolar epithelial cell line A-549. Candidate molecules
      were chosen on the basis of their previously observed protective effects in
      vitro. The tested compounds, including antioxidants, sulfhydryl or other sulfur
      containing molecules, nitrogen-containing molecules, PARP inhibitors and a NO
      synthase inhibitor, were applicated 30min before SM treatment. The efficiency of
      candidate molecules to protect cells against DNA damage and cell death induced by
      SM was determined using single-cell gel electrophoresis (comet assay) and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by viable
      cells. The damage of DNA was assessed 1 and 24h after dose 50MUM SM. Cell
      survival was assessed 24 and 72h after the exposure. To achieve maximal
      cytoprotection, combinations of selected compounds with sodium 2-mercaptoethane
      sulphonate (MESNA) were tested. We found significant protective effects by
      several drugs used individually and also in combination with MESNA. High
      protection was achieved by sodium thiosulphate, which was further potentiated
      when combined with MESNA. Most of the selected compounds or mixture provided only
      moderate genoptotection without having any effect towards cell viability.

PMID- 28495615
TI  - A novel function of TLR4 in mediating the immunomodulatory effect of
      Benzanthrone, an environmental pollutant.
AB  - Our prior studies have reported that Benzanthrone (BA) manifests inflammatory
      responses in the spleen of Balb/c mice. The present investigation was carried out
      to study the impact of BA on macrophages, which are the primary scavenger cells
      in the body that act as a connecting link between innate and adaptive immunity.
      Parenteral administration of BA (daily for one week) to mice resulted in enhanced
      levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2,
      MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class
      II receptors were down regulated. Further, the potential membrane receptor
      targets (TLRs) of BA and its interaction with TLRs was investigated using
      computational methods. Professional phagocytes play pivotal roles in sensing
      bacteria through pathogen-associated molecular patterns (PAMPs) by various
      pathogen recognition receptors (PRRs), including Toll-like receptors (TLRs).
      Several studies have implicated these TLRs in the amplification of the
      inflammatory responses, however the fundamental role played by TLRs in mediating
      the inflammation associated with xenobiotics is still obscure and not understood.
      From the in silico analysis, it was evident that BA showed the highest binding
      affinity with TLR4 as compared to other TLRs. The western blotting studies
      confirmed that BA exposure indeed upregulated the expression of TLR 4, 5 and 9.
      Moreover, the downstream signaling cascade proteins of TLRs such as myeloid
      differentiation primary response protein-88 (MyD88), IL-1 receptor associated
      kinase (IRAK-1), and TNFR-associated factor (TRAF-6) were found to be enhanced in
      the BA treated groups. It was also observed that BA treatment increased the
      expression of ICAM-1, p-Lyn, p-Syk, p-PI3-K, IP3, PLC-gamma, cAMP and Ca+2
      influx, which are known to play a critical role in TLR mediated inflammation.
      Earlier we found that toxic effects of BA in spleen were mediated by oxidative
      stress which was partially neutralized by NAC exposure. Hereby, we report that
      NAC treatment in conjunction with BA attenuated the expression of BA induced
      TLR4, as well as the inflammatory markers such as COX2 and p-NFkB in macrophages.
      These findings demonstrated the critical role of TLRs in the regulation of the BA
      induced inflammation.

PMID- 28495616
TI  - Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3
      and TRPC6 mediated Ca2+ overload in rat cardiomyocytes.
AB  - Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that
      leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress
      has been suggested to be an important contributor to myocardium dysfunction
      during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B)
      protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress
      and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not
      yet clearly. In this study, we investigated the protective effect and mechanisms
      of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro.
      After pretreatment with Sal B (0.25, 0.5, 1mg/kg i.v.) for 7 days, male SD rats
      were intraperitoneally injected with a single dose of DOX (3mg/kg) every 2 days
      for three injections. The cardioprotective effect of Sal B was observed 2 weeks
      after the first administration. Adult rat ventricular myocytes were isolated and
      treated with Sal B (20MUg/ml) for 6h and then exposed in DOX (1MUm) for 4h. The
      cardiomyocyte contractility and the level of intracellular Ca2+ were determined.
      Sal B ameliorated DOX-induced apoptosis damage in heart tissues. In vitro studies
      showed that DOX induced adult rat ventricular myocytes contractile dysfunction
      and intracellular Ca2+ handling derangement, disrupted mitochondrial membrane
      potential, raised the level of ER stress related proteins. However, Sal B
      pretreatment suppressed all of these adverse effects of DOX. The effects of Sal B
      were closely related to the inhibition of transient receptor potential canonical
      (TRPC) channels, as characterized by inhibiting the expression of TRPC 3 and
      TRPC6. These results indicate that Sal B protects against DOX-induced cardiac
      apoptosis and ER stress via TRPC3 and TRPC6 inhibition.

PMID- 28495617
TI  - The adaptor protein ARA55 and the nuclear kinase HIPK1 assist c-Myb in recruiting
      p300 to chromatin.
AB  - LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs,
      have been shown to play diverse roles in several cellular processes. A common
      theme is that they mediate important protein-protein interactions that are key to
      their function. Androgen receptor-associated protein 55 (ARA55) belongs to this
      family of bridging proteins containing four C-terminal LIM domains. It has a dual
      role with functions both at focal adhesions and in the nucleus, apparently
      shuttling between the two compartments. In the present work, we have expanded our
      understanding of its nuclear functions by showing that it interacts with three
      nuclear regulators not previously linked to ARA55. We first identified ARA55 as a
      novel interaction partner of the nuclear kinase HIPK1 and found that ARA55, like
      HIPK1, also interacts with the transcription factor c-Myb. In search of a
      function for these associations, we observed that the coactivator p300 not only
      binds to c-Myb, but to ARA55 as well. When combined, c-Myb, p300, HIPK1 and ARA55
      caused strong synergistic activation of a chromatinized reporter gene. In
      parallel, all partners, including p300, were efficiently recruited to chromatin
      at the c-Myb-bound promoter. Consistent with this cooperation, we found that c
      Myb and ARA55 share a common set of target genes in an osteosarcoma cellular
      context. We propose that ARA55 and HIPK1 assist c-Myb in recruiting the
      coactivator and acetyltransferase p300 to chromatin.

PMID- 28495618
TI  - A model of acute renal allograft rejection in outbred Yorkshire piglets.
AB  - Pigs represent a desirable animal model for the study of rejection in kidney
      transplantation with inbred Yucatan miniature swine (YMS) the most commonly
      studied strain due to well defined swine leukocyte antigen (SLA) genotypes.
      However, limitations to YMS may include cost and availability. Outbred Yorkshire
      pigs are widely available and significantly cheaper than YMS. Recent advances in
      SLA genotyping have allowed its application to outbred strains. On this basis, we
      theorized that Yorkshire pigs would be a viable alternative to YMS for the study
      of rejection in kidney transplantation. To address this question, we performed
      auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA
      genotypes and acute rejection after 72h. At sacrifice, and when compared to
      autotransplants, allotransplants had significant elevations in serum creatinine
      (8.4+/-1.3 vs 2.8+/-2.0mg/dL for Allo vs autotransplants, respectively) and BUN
      (61+/-9 vs 19.2+/-15mg/dL for Allo vs autotransplants, respectively). Warm
      ischemia times between the two groups did not differ (24+/-2.3 vs 26.4+/-1.4min
      for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified
      from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all
      allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the
      most common. One allograft demonstrated hyperacute rejection due a blood group
      incompatibility. Histologically, the expression of regulatory Tcells and
      dendritic cells was increased in allografts. These data suggest that Yorkshire
      pigs may be a useful model for the study of acute rejection in experimental
      kidney transplantation.

PMID- 28495619
TI  - The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled
      trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non
      cystic fibrosis bronchiectasis.
AB  - : The primary goals of long-term disease management in non-cystic fibrosis
      bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve
      quality of life. However, currently no therapies are licensed for this.
      Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be
      the first long-term intermittent therapy approved to reduce exacerbations in NCFB
      patients. The RESPIRE programme consists of two international phase III
      prospective, parallel-group, randomized, double-blinded, multicentre, placebo
      controlled trials of the same design. Adult patients with idiopathic or post
      infectious NCFB, a history of >=2 exacerbations in the previous 12months, and
      positive sputum culture for one of seven pre-specified pathogens, undergo
      stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or
      placebo using a pocket-sized inhaler in one of two regimens: 28days on/off
      treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8
      week follow-up after the last dose. The primary efficacy endpoints are time to
      first exacerbation after treatment initiation and frequency of exacerbations
      using a stringent definition of exacerbation. Secondary endpoints, including
      frequency of events using different exacerbation definitions, microbiology,
      quality of life and lung function will also be evaluated. The RESPIRE trials will
      determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria
      and stratified randomization, the inclusion of two treatment regimens and a
      stringent definition of exacerbation should clarify the patient population best
      positioned to benefit from long-term inhaled antibiotic therapy. Additionally
      RESPIRE will increase understanding of NCFB treatment and could lead to an
      important new therapy for sufferers. TRIAL REGISTRATION: The RESPIRE trials are
      registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of
      registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration
      April 4, 2014).

PMID- 28495621
TI  - A reusable multipurpose magnetic nanobiocatalyst for industrial applications.
AB  - A multipurpose magnetic nanobiocatalyst is developed by conjugating Pectinex 3XL
      (a commercial enzyme containing pectinase, xylanase and cellulase activities) on
      3-aminopropyl triethoxysilane activated magnetic nanoparticles. The
      nanobiocatalyst retained 87% of pectinase, 69% of xylanase and 58% of cellulase
      activity after conjugation on modified nanoparticles as compared to their soluble
      counterparts. Thermal stability data at 70 degrees C showed increase in enzyme
      stability after conjugation to nanoparticles and the kinetic parameters (Km and
      Vmax) remain unaltered after immobilization. The immobilized enzyme system can be
      successfully used upto 5th cycle after that slight decrease in enzyme activities
      was observed. The nanobiocatalyst retained high pectinase activities in organic
      solvents and chemical reagents as compared to free enzymes. DLS data shows that
      the nanoparticles size increases from 63nm to 86nm after immobilization. Atomic
      Force Microscopy data confirms the deposition of enzymes on the nanoparticles.
      The nanobiocatalyst was used for the clarification of pine apple and orange juice
      and was also used for the production of bioethanol. Hydrolysis of pretreated
      wheat straw produced 1.39g/l and 1.59g/l after treatment with free Pectinex 3xL
      and nanobiocatalyst respectively. The concentration of bioethanol also increases
      by 1.4 fold as compared to the free enzyme.

PMID- 28495622
TI  - A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation,
      partial characterization, and assessment of pro-apoptotic and antiprotozoal
      activities.
AB  - A new l-amino acid oxidase (LAAO) from Bothrops jararacussu venom (BjussuLAAO-II)
      was isolated by using a three-step chromatographic procedure based on molecular
      exclusion, hydrophobicity, and affinity. BjussuLAAO-II is an acidic enzyme with
      pI=3.9 and molecular mass=60.36kDa that represents 0.3% of the venom proteins and
      exhibits high enzymatic activity (4884.53U/mg/mim). We determined part of the
      primary sequence of BjussuLAAO-II by identifying 96 amino acids, from which 34
      compose the N-terminal of the enzyme (ADDRNPLEECFRETDYEEFLEIARNGLSDTDNPK).
      Multiple alignment of the partial BjussuLAAO-II sequence with LAAOs deposited in
      the NCBI database revealed high similarity (95-97%) with other LAAOs isolated
      from Bothrops snake venoms. BjussuLAAO-II exerted a strong antiprotozoal effect
      against Leishmania amazonensis (IC50=4.56MUg/mL) and Trypanosoma cruzi
      (IC50=4.85MUg/mL). This toxin also induced cytotoxicity (IC50=1.80MUg/mL) and
      apoptosis in MCF7 cells (a human breast adenocarcinoma cell line) by activating
      the intrinsic and extrinsic apoptosis pathways, but were not cytotoxic towards
      MCF10A cells (a non-tumorigenic human breast epithelial cell line). The results
      reported herein add important knowledge to the field of Toxinology, especially
      for the development of new therapeutic agents.

PMID- 28495620
TI  - Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function
      (VCSIP): Rationale, design, and methods of a randomized, controlled trial of
      vitamin C supplementation in pregnancy for the primary prevention of effects of
      in utero tobacco smoke exposure on infant lung function and respiratory health.
AB  - Despite strong anti-smoking efforts, at least 12% of American women cannot quit
      smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly.
      Smoking during pregnancy is the largest preventable cause of childhood
      respiratory illness including wheezing and asthma. Recent studies have shown a
      protective effect of vitamin C supplementation on the lung function of offspring
      exposed to in utero smoke in a non-human primate model and an initial human
      trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung
      Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to
      evaluate pulmonary function at 3months of age in infants delivered to pregnant
      smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy.
      Secondary aims evaluate the incidence of wheezing through 12months and pulmonary
      function testing at 12months of age. Women are randomized between 13 and 23weeks
      gestation from clinical sites in Portland, Oregon at Oregon Health & Science
      University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana
      at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from
      randomization to delivery. Monthly contact with participants and monitoring of
      medical records is performed to document medication adherence, changes in smoking
      and medical history, and adverse events. Pulmonary function testing of offspring
      occurs at 3 and 12months of age and incidence of wheezing and respiratory illness
      through 12months is captured via at least quarterly questionnaires. Ancillary
      studies are investigating the impact of vitamin C on placental blood flow and DNA
      methylation.

PMID- 28495623
TI  - Polycaprolactone nanocomposite reinforced by bioresource starch-based
      nanoparticles.
AB  - Biodegradable polymer nanocomposites with bioresource starch-based nanoparticles
      (SNPs) as reinforcing fillers for polycaprolactone (PCL) were prepared by melt
      blending. Scanning electron microscopy observation revealed that SNPs as
      spherical particles were evenly dispersed in the PCL matrix without any
      aggregation even with the content of SNPs increasing to 10wt% in the
      nanocomposite. Consequently, the rheological performances of PCL have been
      improved efficaciously after incorporation with SNPs as well as mechanical
      properties, especially with a percolation network structure of SNPs in the PCL
      matrix formed. In addition, the enzymatic hydrolysis experiments showed a more
      interesting behavior that the hydrolysis rates had been accelerated apparently in
      the nanocomposites than that in the neat PCL as observed. Such high performance
      nanocomposites may have great potential in expanding the utilization of starch
      from sustainable resources and the practical application of PCL-based
      biodegradable materials.

PMID- 28495624
TI  - Mechanistic insight into interaction of Sodium Dodecyl Sulphate to asialylated
      form of glycoprotein: A mimic of membrane protein-lipid system.
AB  - The SDS-glycoprotein system is mimic of membrane protein-lipid system. Fate of
      glycoprotein, conformation and the interactive forces involved in membrane milieu
      are expected to be decided by the net charge on glycoprotein that may change
      during acidic environment in a range of pathological states, including cancer,
      stroke, and ischemia. Asialofetuin (ASF; asialylated form of glycoprotein) and
      SDS interaction is studied when glycoprotein bears varying range of net charge
      (i.e. at different pH's) by steady state and time-resolved spectroscopic,
      calorimetric and microscopic approaches. SDS interacts differently with ASF when
      protein is in cationic (at pH 2, 3 and 4) and in anionic states (pH 7.4). ASF
      undergo aggregation at pH 2, 3 and 4 whereas have enhancement in alpha-helical
      structure at pH 7.4 at sub-micellar concentrations of SDS. At pH 2, 3 and 4, the
      positively charged ASF interacts electrostatically with negatively charged head
      groups of SDS, leaving its hydrophobic tail free to interact with other protein
      SDS complex and consequently lead to amyloid formation. However, at pH 7.4, the
      ASF interacts hydrophobically with SDS and an increase in alpha-helical content
      occurs that constrains the environment of Trp51 and consequently decreases
      movement of Trp conformers.

PMID- 28495625
TI  - Nickel nanoparticle synthesis using Camellia Sinensis as reducing and capping
      agent: Growth mechanism and photo-catalytic activity evaluation.
AB  - Recently, the biosynthesis of nanoparticle attracted the attention of scientific
      community due to its simplicity, ease and eco-friendly nature. In the present
      study, Camellia Sinensis (C. Sinensis) leaves extract was employed for the
      synthesis of nickel nanoparticles (NiNPs). The fabricated NiNPs were
      characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray
      (EDX) and X-ray diffraction techniques. The photocatalytic activity (PCA) was
      evaluated by degrading crystal violet (CV) dye. The NiNPs size was in the range
      of 43.87-48.76nm, spherical in shape and uniformly distributed with magnetization
      saturation of 0.073 emu/g. The NiNPs showed promising PCA under solar light
      irradiation. At optimized conditions, up to 99.5% CV dye degradation was
      achieved. Results revealed that biosynthesis can be adopted for the synthesis of
      NiNPs in nano-size range since it is simple, cost effective and eco-friendly in
      nature versus physico-chemical methods.

PMID- 28495626
TI  - Promising biocidal activity of thymol loaded chitosan silver nanoparticles (T
      C@AgNPs) as anti-infective agents against perilous pathogens.
AB  - The advent of biodegradable polymer-encapsulated drug nanoparticles has made an
      exciting area of drug delivery research. The present study investigated novel and
      simple route for synthesis of thymol loaded chitosan silver nanoparticles (T
      C@AgNPs) using chitosan and thymol as reducing, capping agent respectively to
      understand the therapeutic efficacy. The UV-vis spectroscopy, DLS, FT-IR, SEM,
      EDS, XRD used for characterization and radical scavenging activity, anti
      microbial and biocompatibility was taken to ascertain an efficacy of novel T
      C@AgNPs. The T-C@AgNPs intense peak at 490nm indicates the formation of
      nanoparticles and had average particle size of 28.94nm with spherical shape,
      monodisperse state in water, also exhibited excellent biocompatibility of cubic
      shaped pure silver element containing T-C@AgNPs. The antibacterial activity was
      studied for gram positive and gram negative food-borne pathogens and effective
      inhibition at 100MUgmL-1 to S. aureus, S. epidermidis, S. haemolyticus (10.08,
      10.00, 11.23mm) and S. typhimurium, P. aeruginosa and S. flexneri (9.28, 9.33,
      12.03mm) compared to antibiotic Streptomycin. This study revealed the efficacy
      against multiple food-borne pathogens and therapeutic efficacy of T-C@AgNPs
      offers a valuable contribution in the area of nanotechnology. This proved to be a
      first-class novel antimicrobial material for the first time in this study.

PMID- 28495627
TI  - Effects of site-specific phosphorylation on the mechanical properties of
      ovalbumin-based hydrogels.
AB  - An efficient one-step grafting approach was developed to modify ovalbumin (OVA)
      by phosphorylation through selective reaction with the hydroxyl group of Ser and
      Thr residues present in OVA. The site-specific phosphorylated conjugates were
      characterized by Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass
      Spectrometry (MALDI-TOF/MS) and the results indicated that the Ser residue could
      be more readily phosphorylated, and the typical phosphopeptides
      264LTEWTSSNVMEER276 and 340EVVGSAEAGVDAASVSEEFR359 demonstrated the formation of
      monophosphoester. Moreover, 13C NMR analysis showed that the betaCH2 of Ser acted
      as a hydroxyl donor to react with sodium tripolyphosphate (STPP), and the
      conjugates with variable phosphorylation sites could improve the weak network and
      the resulting poor mechanical properties of ovalbumin-based hydrogels.
      Furthermore, small-amplitude oscillatory measurements, creep recovery tests and
      texture profile analysis of hardness and stickiness indicated that
      phosphorylation can strengthen the intermolecular cross-linking of protein
      molecules and produce significant influence on the rheological behavior and
      texture properties, suggesting that a suitable conjugation site is essential for
      the best gelation properties at a different pH. The integrated results indicate
      that phosphorylation change significantly modify the viscoelastic and mechanical
      properties of OVA-based hydrogels by changing molecular dynamics upon heating.

PMID- 28495628
TI  - Optimization of functional nanoparticles formation in associative mixture of
      water-soluble portion of Farsi gum and beta-lactoglobulin.
AB  - Electrostatic interaction between beta-lactoglobulin (beta-Lg) and water-soluble
      fraction of Farsi gum (WSFPG) was studied under the influence of pH, beta
      Lg:WSFPG mixing ratio (MR) and total concentration (TC) through performing
      various experiments such as turbidity, particle size and zeta potential
      measurements. Changes in the relative viscosity during in-situ acidification were
      studied at various ionic strengths. Lower amounts of absorbance and sedimentation
      were observed by decreasing the MR. An increase in the TC increased the
      absorbance of complexed samples. The smallest particle sizes, obtained at a same
      MR (1:3), were 108 and 188nm at TCs of 0.1 and 0.3wt%, respectively. The
      decreased relative viscosity upon acidification was a proof for the wrapping
      phenomenon in the biopolymer mixture. A further decrease in the relative
      viscosity was observed at higher ionic strength. The results of this study may
      facilitate the rational design of functional nanoparticles in associative
      mixtures of beta-Lg and WSFPG.

PMID- 28495629
TI  - Improving stability and reusability of Rhodococcus pyridinivorans NIT-36
      nitrilase by whole cell immobilization using chitosan.
AB  - Immobilized enzymes have great significance for industrial processes. In this
      study whole cell immobilization of Rhodococcus pyridinivorans NIT-36 has been
      undertaken using chitosan microspheres as an immobilized matrix. R.
      pyridinivorans NIT-36 harbors a significant intracellular enzyme nitrilase.
      Chitosan microspheres were generated by supplementing chitosan with
      glutaraldehyde and results, supported the porous microsphere structure via SEM.
      The resultant microspheres exhibited cell immobilization capacity of 450mg/g. The
      immobilized cells exhibited a considerable increase in temperature tolerance at
      60 degrees C as compared to free cells. The immobilized microspheres also
      demonstrated higher substrate tolerance. The immobilized nitrilase retained 80%
      activity when stored at 4 degrees C for 10 days and retained 50% activity after 7
      reuse cycles. It may be concluded that chitosan microspheres are a novel
      immobilization agent for whole cell immobilization which enhances the stability
      and reusability of nitrilase enzyme.

PMID- 28495630
TI  - alpha-chymotrypsin activated and stabilized by self-assembled polypseudorotaxane
      fabricated with bis-thiolated poly(ethylene glycol) and alpha-cyclodextrin:
      Spectroscopic and mechanistic analysis.
AB  - The self-assembled polypseudorotaxane (PPRX) fabricated with bis-thiolated
      poly(ethylene glycol) (PEG) and alpha-cyclodextrin (alpha-CyD) acted as an
      activator for alpha-chymotrypsin (CT) and retained the activity of CT for a long
      time up to 7days. The stabilization mechanism was studied, and the interaction
      between CT and PPRX was analyzed by using circular dichroism, fluorescence
      spectra and X-ray powder diffraction (XRD). The bis-thiolated PEG and its
      assembled PPRX with alpha-CyD exhibited the interaction with the C-terminal
      region of the CT's B-chain probably through PEGylation of the surface disulfide
      bridge of CT. It caused the aromatic chromophores more exposed to the hydrophilic
      microenvironment, leading to conformational variation of CT that was revealed by
      spectroscopic analysis. It rendered the peptide chains in a more flexible and
      active state. As a comparison, the non-thiolated components could not decorate
      the surface of CT and performed almost no effect on its stability, which
      demonstrated that the decoration of the surface disulfide bridge was a key factor
      in retaining the activity of CT. Due to the activation and stabilization effect,
      bis-thiolated PEG/alpha-CyD PPRX was an excellent soft-immobilized carrier for
      CT, and provided an intriguing method for enzyme's stabilization.

PMID- 28495631
TI  - Synthesis and characterization of Ag2S decorated chitosan nanocomposites and
      chitosan nanofibers for removal of lincosamides antibiotic.
AB  - We report the synthesis of Ag2S-Chitosan nanocomposites and Ag2S-chitosan
      nanohybrids as performance adsorbents for Lincosamides such as Clindamycin
      antibiotic removal. Isotherms and kinetic studies were determined to understand
      the adsorption behavior both two adsorbent. At low adsorbent dose, removals are
      increased in the adsorption process, and performance is better with Ag2S-chitosan
      nanohybrids due to the special surface area increased. The average sizes and
      surface area of Ag2S-Chitosan nanocomposites and Ag2S-chitosan nanohybrids were
      found as 50nm, 70nm and 180.18, 238.24m2g-1, respectively. In particular, Ag2S
      Chitosan nanocomposites and Ag2S-chitosan nanohybrids show high maximum
      Clindamycin adsorption capacity (qmax) of 153.21, and 181.28mgg-1, respectively.
      More strikingly, Ag2S-Chitosan nanocomposites and Ag2S-chitosan nanohybrids are
      also demonstrated to nearly completely remove Clindamycin from drinking water.
      The excellent adsorption performance along with their cost effective, convenient
      synthesis makes this range of adsorbents highly promising for commercial
      applications in drinking water and wastewater treatment.

PMID- 28495632
TI  - Evaluation of dermal wound healing activity and in vitro antibacterial and
      antioxidant activities of a new exopolysaccharide produced by Lactobacillus
      sp.Ca6.
AB  - The present study aimed to evaluate the in vitro antibacterial and antioxidant
      activities and the in vivo wound healing performance of a noval
      exopolysaccharides (EPS-Ca6) produced by Lactobacillus sp.Ca6 strain. The results
      showed that EPS-Ca6 had a potential antioxidant activity determined through four
      different assays: DPPH scavenging activity, reducing power, beta-carotene
      bleaching by linoleic acid assay, and Metal chelating activities. It also
      exhibited significant antibacterial activity against pathogenic bacteria
      Salmonella enterica and Micrococcus luteus. The wound healing activity of the EPS
      Ca6, using excision wound model in rats, showed that this novel EPS accelerated
      significantly wound healing activity as compared to the control group, and a
      total closure was achieved after 14days of wound induction. Furthermore,
      histological examination of biopsies showed fully re-epithelialized wound with a
      complete epidermal regeneration. Overall the finding indicates that the EPS-Ca6
      might be useful as a wound healing agent in modern medicine.

PMID- 28495633
TI  - Mechanical reinforcement of gelatin hydrogel with nanofiber cellulose as a
      function of percolation concentration.
AB  - Given a variety of distinguished aspect ratio-related characteristics of
      nanofiber cellulose (NFC), the impact of NFC on gelatin hydrogel performance
      involving strength, rheology, microstructure was investigated, focusing on
      concentration percolation mechanism for it. The inner topography displayed a
      compact three-dimensional network structure in the NFC-added gelatin gel,
      however, an NFC amount of 7.5gkg-1 caused more inhomogeneous aggregation. Texture
      profile analysis showed that the addition of NFC increased the hardness but
      reduced the elasticity of gelatin gel at 10 degrees C, depending on NFC
      concentration. For static rheology, adding NFC transformed gelatin solution from
      the Newtonian action into pseudoplastic behavior at 60 degrees C, with a marked
      increase of viscosity. Furthermore, NFC improved the temperature of sol-gel
      transition of gelatin, even no obvious transformation as >=5gkg-1 NFC used. NFC
      reinforcement provides the potential to use as texture modifier along with
      gelatin in food field.

PMID- 28495635
TI  - Can we detect the effect of spines and leaflets on the diffusion of brain
      intracellular metabolites?
AB  - Prior models used to clarify which aspects of tissue microstructure mostly affect
      intracellular diffusion and corresponding diffusion-weighted magnetic resonance
      (DW-MR) signal have focused on relatively simple geometrical descriptions of the
      cellular microenvironment (spheres, randomly oriented cylinders, etc...),
      neglecting finer morphological details which may have an important role. Some
      types of neurons present high density of spines; and astrocytes and macroglial
      cells processes present leaflets, which may all impact the diffusion process.
      Here, we use Monte-Carlo simulations of many particles diffusing in cylindrical
      compartments with secondary structures mimicking spines and leaflets of neuronal
      and glial cell fibers, to investigate to what extent the diffusion-weighted
      signal of intracellular molecules is sensitive to spines/leaflets density and
      length. In order to study the specificity of DW-MR signal to these kinds of
      secondary structures, beading-like geometry is simulated as "control" deviation
      from smooth cylinder too. Results suggest that: a) the estimated intracellular
      tortuosity increases as spines/leaflets density or length (beading amplitude)
      increase; b) the tortuosity limit is reached for diffusion time td>200 ms for
      metabolites and td>70 ms for water molecules, suggesting that the effects of
      these finer morphological details are negligible at td longer than these
      threshold values; c) fiber diameter is overestimated, while intracellular
      diffusivity is underestimated, when simple geometrical models based on hollow
      smooth cylinders are used; d) apparent surface-to-volume, S/V, ratio estimated by
      linear fit of high frequency OG data appears to be an excellent estimation of the
      actual S/V ratio, even in the presence of secondary structures, and it increases
      as spines and leaflets density or length increase (while decreasing as beadings
      amplitude increases). Comparison between numerical simulations and multimodal
      metabolites DW-MRS experiments in vivo in mouse brain shows that these fine
      structures may affect the DW-MRS signal and the derived diffusion metrics
      consistently with their expected density and geometrical features. This work
      suggests that finer structures of cell morphology have non-negligible effects on
      intracellular molecules' diffusion that may be measured by using multimodal DW
      MRS approaches, stimulating future developments and applications.

PMID- 28495636
TI  - Optimal experimental designs for fMRI when the model matrix is uncertain.
AB  - This study concerns optimal designs for functional magnetic resonance imaging
      (fMRI) experiments when the model matrix of the statistical model depends on both
      the selected stimulus sequence (fMRI design), and the subject's uncertain
      feedback (e.g. answer) to each mental stimulus (e.g. question) presented to
      her/him. While practically important, this design issue is challenging. This
      mainly is because that the information matrix cannot be fully determined at the
      design stage, making it difficult to evaluate the quality of the selected
      designs. To tackle this challenging issue, we propose an easy-to-use optimality
      criterion for evaluating the quality of designs, and an efficient approach for
      obtaining designs optimizing this criterion. Compared with a previously proposed
      method, our approach requires a much less computing time to achieve designs with
      high statistical efficiencies.

PMID- 28495634
TI  - Network-targeted cerebellar transcranial magnetic stimulation improves
      attentional control.
AB  - Developing non-invasive brain stimulation interventions to improve attentional
      control is extremely relevant to a variety of neurological and psychiatric
      populations, yet few studies have identified reliable biomarkers that can be
      readily modified to improve attentional control. One potential biomarker of
      attention is functional connectivity in the core cortical network supporting
      attention - the dorsal attention network (DAN). We used a network-targeted
      cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance
      cortical functional connectivity in the DAN. Specifically, in healthy young
      adults we administered intermittent theta burst TMS (iTBS) to the midline
      cerebellar node of the DAN and, as a control, the right cerebellar node of the
      default mode network (DMN). These cerebellar targets were localized using
      individual resting-state fMRI scans. Participants completed assessments of both
      sustained (gradual onset continuous performance task, gradCPT) and transient
      attentional control (attentional blink) immediately before and after stimulation,
      in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation,
      participants had significantly fewer attentional lapses (lower commission error
      rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not
      affect gradCPT performance. Further, in the DAN condition, individuals with worse
      baseline gradCPT performance showed the greatest enhancement in gradCPT
      performance. These results suggest that temporarily increasing functional
      connectivity in the DAN via network-targeted cerebellar stimulation can enhance
      sustained attention, particularly in those with poor baseline performance. With
      regard to transient attention, TMS stimulation improved attentional blink
      performance across both stimulation sites, suggesting increasing functional
      connectivity in both networks can enhance this aspect of attention. These
      findings have important implications for intervention applications of TMS and
      theoretical models of functional connectivity.

PMID- 28495637
TI  - Veridical stimulus localization is linked to human area V5/MT+ activity.
AB  - How the brain represents visual space is an unsolved mystery. Spatial
      localization becomes particularly challenging when visual information processing
      is briefly disrupted, as in the case of saccadic eye movements, blinks, or visual
      masks. As we have recently reported, a compression of visual space, illustrated
      by displacements of shortly flashed stimuli, can be observed in the temporal
      vicinity of masking stimuli during ocular fixation (Zimmermann et al., 2013). We
      here aimed at investigating the neural mechanisms underlying these displacements
      using functional magnetic resonance imaging. On the behavioral level, we detected
      significant stimulus displacement when visual masks were simultaneously
      presented. At the neural level, we observed decreased human motion complex V5/MT+
      activation associated with these displacements: When comparing trials with a
      perceived stimulus shift in space to trials of veridical perception of stimulus
      localization, human V5/MT+ was significantly less activated although no
      differences in perceived motion can account for this. Data suggest an important
      role of human V5/MT+ in the process of spatial localization of briefly presented
      objects and thus extend current concepts of the functions of human V5/MT+.

PMID- 28495638
TI  - Targeting metabolism in pancreatic cancer.

PMID- 28495640
TI  - Sources of Hematopoietic Stem and Progenitor Cells and Methods to Optimize Yields
      for Clinical Cell Therapy.
AB  - Bone marrow (BM) aspirates, mobilized peripheral blood, and umbilical cord blood
      (UCB) have developed as graft sources for hematopoietic stem and progenitor cells
      (HSPCs) for stem cell transplantation and other cellular therapeutics.
      Individualized techniques are necessary to enhance graft HSPC yields and cell
      quality from each graft source. BM aspirates yield adequate CD34+ cells but can
      result in relative delays in engraftment. Granulocyte colony-stimulating factor
      (G-CSF)-primed BM HSPCs may facilitate faster engraftment while minimizing graft
      versus-host disease in certain patient subsets. The levels of circulating HSPCs
      are enhanced using mobilizing agents, such as G-CSF and/or plerixafor, which act
      via the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 axis.
      Alternate niche pathway mediators, including very late antigen-4/vascular cell
      adhesion molecule-1, heparan sulfate proteoglycans, parathyroid hormone, and
      coagulation cascade intermediates, may offer promising alternatives for graft
      enhancement. UCB grafts have been expanded ex vivo with cytokines, notch-ligand,
      or mesenchymal stromal cells, and most studies demonstrated greater quantities of
      CD34+ cells ex vivo and improved short-term engraftment. No significant changes
      were observed in long-term repopulating potential or in patient survival. Early
      phase clinical trials using nicotinamide and StemReginin1 may offer improved
      short- and long-term repopulating ability. Breakthroughs in genome editing and
      stem cell reprogramming technologies may hasten the generation of pooled, third
      party HSPC grafts. This review elucidates past, present, and potential future
      approaches to HSPC graft optimization.

PMID- 28495639
TI  - Safety and tolerability of the first-in-class agent CPI-613 in combination with
      modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single
      centre, open-label, dose-escalation, phase 1 trial.
AB  - BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of
      less than 10%, and more than 50% of patients presenting with metastatic disease.
      Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI
      613 is a novel anticancer agent that selectively targets the altered form of
      mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial
      enzyme activities and redox status that lead to apoptosis, necrosis, and
      autophagy of tumour cells. We aimed to establish the maximum tolerated dose of
      CPI-613 when used in combination with modified FOLFIRINOX chemotherapy
      (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients
      with metastatic pancreatic cancer. METHODS: In this single-centre, open-label,
      dose-escalation phase 1 trial, we recruited adult patients (aged >=18 years) with
      newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive
      Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA).
      Patients had good bone marrow, liver and kidney function, and good performance
      status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We
      studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2,
      leucovorin at 400 mg/m2, irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2
      bolus followed by 2400 mg/m2 over 46 h). We applied a two-stage dose-escalation
      scheme (single patient and traditional 3+3 design). In the single-patient stage,
      one patient was accrued per dose level. The starting dose of CPI-613 was 500
      mg/m2 per day; the dose level was then escalated by doubling the previous dose if
      there were no adverse events worse than grade 2 within 4 weeks attributed as
      probably or definitely related to CPI-613. The traditional 3+3 dose-escalation
      stage was triggered if toxic effects attributed as probably or definitely related
      to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort
      in the traditional dose-escalation stage was the same as that used in the last
      cohort of the single-patient dose-escalation stage. The primary objective was to
      establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting
      toxicities). This trial is registered with ClinicalTrials.gov, number
      NCT01835041, and is closed to recruitment. FINDINGS: Between April 22, 2013, and
      Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was
      500 mg/m2. The median number of treatment cycles given at the maximum tolerated
      dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the
      maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a
      higher dose of 1000 mg/m2, and both had a dose-limiting toxicity. Two unexpected
      serious adverse events occurred, both for the first patient enrolled. Expected
      serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for
      patient number 2; anaemia and lymphopenia were dose-limiting toxicities);
      hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis
      (patient number 11); and neutropenia (patient number 20). No deaths due to
      adverse events were reported. For the 18 patients given the maximum tolerated
      dose, the most common grade 3-4 non-haematological adverse events were
      hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory
      neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]).
      The most common grade 3-4 haematological adverse events were neutropenia (five
      [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and
      thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded
      in 17 (94%) of the 18 patients and was managed with dose de-escalation or
      discontinuation per standard of care. No patients died while on active treatment;
      11 study participants died, with cause of death as terminal pancreatic cancer. Of
      the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective
      (complete or partial) response. INTERPRETATION: A maximum tolerated dose of CPI
      613 was established at 500 mg/m2 when used in combination with modified
      FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of
      clinical activity will require validation in a phase 2 trial. FUNDING:
      Comprehensive Cancer Center of Wake Forest Baptist Medical Center.

PMID- 28495641
TI  - Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory
      Acute Graft-versus-Host Disease.
AB  - Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and
      mortality after allogenic hematopoietic cell transplantation (HCT).
      Corticosteroids are the first-line treatment; however, less than one-half of
      patients achieve durable remission. Studies suggest that TNF-alpha, a cytokine
      released from the bone marrow during conditioning, is involved in the
      pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-alpha
      therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD.
      Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses
      (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17%
      complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14%
      PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had
      infectious complications within 12 weeks of initiation of infliximab. These
      infections included 40 bacterial infections, 6 invasive fungal infections, and 5
      viral reactivations. Twelve patients (34%) died secondary to infections. Overall
      survival at 12 weeks and 6 months from the start of infliximab therapy was 37%
      (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to
      complications from GVHD and infections. In conclusion; the use of infliximab
      therapy in patients with SR-aGVHD is associated with a modest poorly sustained
      response along with a heightened risk of severe infections. Future studies with
      more effective and less toxic therapies are needed for these patients.

PMID- 28495642
TI  - Feasibility of Lenalidomide Therapy for Persistent Chronic Lymphocytic Leukemia
      after Allogeneic Transplantation.
AB  - In patients with chronic lymphocytic leukemia (CLL), persistence of disease after
      allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an
      effort to improve these outcomes, patients with persistent CLL who were 90 to 100
      days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were
      randomized to receive lenalidomide or standard care (withdrawal of
      immunosuppression followed by donor lymphocyte infusion). Lenalidomide was
      initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in
      each patient. Of 38 patients enrolled, 17 (45%) met the eligibility criteria for
      randomization. Of these 17 patients, 8 were randomized to undergo lenalidomide
      therapy. Five (62%) patients had to stop taking the drug because of toxicity. The
      main reason for drug discontinuation was acute GVHD in 43% of patients. This
      incidence was 11% in the patients who were randomized to not receive
      lenalidomide. With a median follow-up of 2.6 years, the median survival was 3.4
      years for those receiving lenalidomide. This was not reached in patients
      randomized to not receive lenalidomide and in patients in complete remission who
      were not randomized. These results suggested that treatments other than
      lenalidomide are needed for persistent CLL after alloSCT.

PMID- 28495643
TI  - Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell
      Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to
      Impaired Antibody Immune Reconstitution.
AB  - Although T cell immune reconstitution after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) has been well studied, long-term B cell immune
      reconstitution remains less characterized. We evaluated humoral immune
      reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid
      antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide
      carbohydrate antibodies remained persistently low for up to 5 years. While naive
      B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for
      up to 2 years (P = .01); switched memory B cell deficiency normalized by 1 year
      after allo-HSCT. CD4+ T cell immune reconstitution correlated with that of
      switched memory B cells as early as 6 months after allo-HSCT (r = .55, P = .002)
      but did not correlate with IgM memory B cells at any time point after allo-HSCT.
      Taken together, this suggests that allo-HSCT recipients have impaired antibody
      immune reconstitution, mainly due to IgM memory B cell maturation block, compared
      with more prompt T cell-dependent switched memory cell immune reconstitution. We
      further explored other factors that might affect humoral immune reconstitution.
      The use of total body irradiation was associated with lower naive B cells counts
      at 6 months after HSCT (P = .04) and lower IgM (P = .008) and switched (P = .003)
      memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft
      versus-host disease had lower IgM memory B cell counts (P = .03) up to 2 years
      after allo-HSCT. The use of cord blood was associated with better naive (P =
      .01), IgM (P = .0005), and switched memory (P = .006) B cells immune
      reconstitution. These findings may inform future prophylaxis and treatment
      strategies regarding risk of overwhelming infection, graft-versus-host disease,
      and post-allogeneic HSCT revaccination.

PMID- 28495644
TI  - Improving core outcome set development: qualitative interviews with developers
      provided pointers to inform guidance.
AB  - OBJECTIVES: The objective of the study was to explore core outcome set (COS)
      developers' experiences of their work to inform methodological guidance on COS
      development and identify areas for future methodological research. STUDY DESIGN
      AND SETTING: Semistructured, audio-recorded interviews with a purposive sample of
      32 COS developers. Analysis of transcribed interviews was informed by the
      constant comparative method and framework analysis. RESULTS: Developers found COS
      development to be challenging, particularly in relation to patient participation
      and accessing funding. Their accounts raised fundamental questions about the
      status of COS development and whether it is consultation or research. Developers
      emphasized how the absence of guidance had affected their work and identified
      areas where guidance or evidence about COS development would be useful including,
      patient participation, ethics, international development, and implementation.
      They particularly wanted guidance on systematic reviews, Delphi, and consensus
      meetings. CONCLUSION: The findings raise important questions about the funding,
      status, and process of COS development and indicate ways that it could be
      strengthened. Guidance could help developers to strengthen their work, but over
      specification could threaten quality in COS development. Guidance should
      therefore highlight common issues to consider and encourage tailoring of COS
      development to the context and circumstances of particular COS.

PMID- 28495645
TI  - Inflammatory pseudotumour of the infratemporal fossa visualized with 18F-FDG
      PET/CT.
AB  - The inflammatory pseudotumour of the head and neck is a benign lesion, extremely
      rare outside the cranial orbits. A case is presented of an inflammatory
      pseudotumour not associated with the IgG4-related disease. The pseudotumour was
      found as a solitary mass in the infratemporal fossa of a young woman who
      complained of otalgia and hearing loss. A clear image of the lesion was obtained
      using an 18F-fluoro-deoxy-glucose (18F-FDG) PET. After the histopathological
      diagnosis, and treatment with corticosteroids, a second 18F-FDG PET was
      performed. The metabolic image had returned to normal, and the previously
      observed mass disappeared. A brief review is presented of the studies examining
      this type of lesion.

PMID- 28495646
TI  - 18F-FDG PET/CT in the detection of a primary radiation-induced metastatic
      angiosarcoma.

PMID- 28495647
TI  - Prevalence of human cosavirus and saffold virus with an emergence of saffold
      virus genotype 6 in patients hospitalized with acute gastroenteritis in Chiang
      Mai, Thailand, 2014-2016.
AB  - Human cosavirus and saffold virus are both newly discovered members of the
      Picornaviridae family. It has been suggested that these viruses may be the
      causative agents of acute gastroenteritis. In this study, 1093 stool samples
      collected from patients with acute gastroenteritis between January 2014 and
      December 2016, were screened for cosavirus and saffold virus using reverse
      transcription-polymerase chain reaction. The viral genotypes were then
      established via nucleotide sequencing. Here, cosavirus was detected in 16 of 1093
      stool samples (1.5%) and saffold virus was detected in 18 of 1093 stool samples
      (1.6%). The saffold virus genotypes 1 (16.7%), 2 (50%) and 6 (33.3%), and the
      cosavirus genetic groups A (87.5%), C (6.25%) and D (6.25%), were all identified
      across the three-year study period. Interestingly, saffold virus genotype 6 has
      now been detected for the first time in Thailand. The present study provides the
      prevalence of cosavirus and saffold virus with the emergence of saffold virus
      genotype 6 in Thailand.

PMID- 28495648
TI  - Complete genome sequences of two avian infectious bronchitis viruses isolated in
      Egypt: Evidence for genetic drift and genetic recombination in the circulating
      viruses.
AB  - Avian infectious bronchitis virus (IBV) is highly prevalent in chicken
      populations and is responsible for severe economic losses to poultry industry
      worldwide. In this study, we report the complete genome sequences of two IBV
      field strains, CU/1/2014 and CU/4/2014, isolated from vaccinated chickens in
      Egypt in 2014. The genome lengths of the strains CU/1/2014 and CU/4/2014 were
      27,615 and 27,637 nucleotides, respectively. Both strains have a common genome
      organization in the order of 5'-UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-UTR
      poly(A) tail-3'. Interestingly, strain CU/1/2014 showed a novel 15-nt deletion in
      the 4b-4c gene junction region. Phylogenetic analysis of the full S1 genes showed
      that the strains CU/1/2014 and CU/4/2014 belonged to IBV genotypes GI-1 lineage
      and GI-23 lineage, respectively. The genome of strain CU/1/2014 is closely
      related to vaccine strain H120 but showed genome-wide point mutations that lead
      to 27, 14, 11, 1, 1, 2, 2, and 2 amino acid differences between the two strains
      in 1a, 1b, S, 3a, M, 4b, 4c, and N proteins, respectively, suggesting that strain
      CU/1/2014 is probably a revertant of the vaccine strain H120 and evolved by
      accumulation of point mutations. Recombination analysis of strain CU/4/2014
      showed evidence for recombination from at least three different IBV strains,
      namely, the Italian strain 90254/2005 (QX-like strain), 4/91, and H120. These
      results indicate the continuing evolution of IBV field strains by genetic drift
      and by genetic recombination leading to outbreaks in the vaccinated chicken
      populations in Egypt.

PMID- 28495649
TI  - Identification and molecular characterization of novel primate bocaparvoviruses
      from wild western lowland gorillas of Moukalaba-Doudou National Park, Gabon.
AB  - Bocaparvoviruses have been studied extensively owing to their ability to cause
      respiratory illness or gastroenteritis in humans. Some bocaparvoviruses have been
      detected in non-human primates (gorillas and chimpanzees), but the diversity and
      evolution of these viruses are not fully understood. In this study, we collected
      107 fecal samples from wild western lowland gorillas in Moukalaba-Doudou National
      Park in Gabon to investigate the presence of bocaparvoviruses. Using a
      combination of pan-bocaparvovirus PCR and individual identification by
      microsatellite genotyping, we found that two samples from two apparently healthy
      infant gorillas were positive for bocaparvovirus. Sequencing and phylogenetic
      analyses revealed that the two gorilla bocaparvovirus strains are nearly
      identical and are closely related to viruses in the species Primate
      bocaparvovirus 2 (with 86.0% nucleotide identity to a human bocavirus 2 isolate).
      To our knowledge, this is the first report showing the presence of a non-human
      primate bocaparovirus within Primate bocaparvovirus 2. Our findings provide novel
      insights into the diversity and evolution of bocaparvoviruses and highlight the
      importance of surveying these viruses for the safe management of gorilla-based
      ecotourism.

PMID- 28495650
TI  - Extent of coronary artery disease in patients undergoing angiography for stable
      or acute coronary syndromes.
AB  - BACKGROUND: We aimed to investigate whether the angiographic extent of coronary
      artery disease (CAD) differs in patients undergoing coronary angiography for
      stable CAD or acute coronary syndrome (ACS) and identify predictors of CAD extent
      in these patients. METHODS: We enrolled 584 consecutive patients (463 with stable
      CAD, 121 with ACS) with angiographically established CAD (>=1 stenosis >25%). The
      Gensini score was used to assess the extent of coronary atherosclerosis. RESULTS:
      Stable CAD patients had greater Framingham risk score and greater prevalence of
      hypertension, hypercholesterolemia, and diabetes (p<0.05 for all). Fasting
      glucose and systolic and diastolic blood pressure were higher, while high
      sensitivity C-reactive protein (hsCRP) levels were lower in patients with stable
      CAD than in those with ACS (p<0.05 for all). No difference in Gensini score was
      observed between the two groups (p=0.118), but patients with ACS were more likely
      to have at least one significant epicardial angiographic lesion (>50% stenosis)
      (OR 2.0, p=0.022). Higher Gensini score was independently associated with (i)
      higher hsCRP and glucose levels, hypercholesterolemia, and increased age in
      stable CAD patients (R2 0.15, p<0001) and (ii) increased age and higher glucose
      and hsCRP levels in patients with ACS (R2 0.17, p<0001). CONCLUSIONS: Patients
      undergoing coronary angiography for ACS or stable CAD presented with a similar
      extent of angiographic CAD, although patients with ACS had a higher prevalence of
      significant lesions in the presence of a better cardiovascular risk profile and
      higher inflammation levels. The extent of angiographic CAD in both the groups
      shared common determinants such as hsCRP, age, and hyperglycemia, but these
      appeared to explain only a small part of the variation of coronary
      atherosclerosis.

PMID- 28495651
TI  - Percentile categorization of QT interval as an approach for identifying adult
      patients at risk for cardiovascular death.
AB  - BACKGROUND: The results from studies of the association of QT prolongation with
      cardiovascular death (CVD) have been inconsistent. OBJECTIVE: The purpose of this
      study was to compare the major correction formulas to percentile values of QT for
      heart rate ranges as to their ability to remove the relationship of QT to heart
      rate and to predict CVD. METHODS: Participants were 16,531 veterans who had an
      initial ECG at the Veterans Affairs Medical Center, Palo Alto, between March 31,
      1987, and December 20, 1999, and were followed for CVD. The 4 major correction
      formulas (Bazett, Fridericia, Framingham, and Hodges) were used to correct QT
      interval. In addition, the percentiles for heart rate ranges as proposed by
      Schwartz were calculated. RESULTS: During median follow-up of 17.8 years, 455 CVD
      events occurred. When compared to the other equations, QTc Bazett had the
      greatest dependence on heart rate (R2 = 0.18). The hazard ratio (95% confidence
      interval) for CVD was 2.08 (1.28-3.9) for the 98th percentile of QT interval by
      heart rate ranges, 2.05 (1.27-3.33) for QTc Bazett, 1.39 (0.44-4.34) for QTc
      Fridericia, 1.05 (0.26-4.24) for QTc Hodges, and 1.12 (0.28-4.52) for QTc
      Framingham. The hazard ratio of QTc Bazett was significantly higher than the
      other formulas except for the 98th percentile method. CONCLUSION: The Framingham,
      Hodges, and Fridericia equations remove the effect of heart rate on QT interval
      significantly better than the Bazett equation. Using QT-interval percentiles
      based on heart rate provides a consistent approach both for identifying those
      whose QT intervals prolong due to drugs or other stressors and for assessing CVD
      risk.

PMID- 28495653
TI  - In search of the holy grail in the channelopathy field: Proving pathogenicity of
      long QT syndrome-associated variants?

PMID- 28495652
TI  - Acute efficacy, safety, and long-term clinical outcomes using the second
      generation cryoballoon for pulmonary vein isolation in patients with a left
      common pulmonary vein: A multicenter study.
AB  - BACKGROUND: Second-generation cryoballoon (CB2)-based pulmonary vein isolation
      (PVI) has demonstrated encouraging clinical results in the treatment of
      paroxysmal (PAF) and persistent atrial fibrillation (PersAF). However, the CB2
      features a maximal diameter of 28 mm, and its adaptability to anatomic variations
      of the pulmonary veins (PVs) might be challenging. OBJECTIVE: The purpose of this
      study was to assess the acute efficacy, safety, and long-term clinical results of
      CB2-based PVI in patients with a left common pulmonary vein (LCPV). METHODS: Six
      hundred seventy consecutive patients underwent CB2-based PVI in 3
      electrophysiology centers. In 74 patients (11%), an LCPV was identified (LCPV
      group). The data were compared to those from matched patients (n = 74) with
      normal PV anatomy and comparable baseline characteristics (control group). An
      antral occlusion of the complete LCPV ostium was feasible in 50% of patients in
      the LCPV group. If an antral occlusion could not be obtained, a sequential
      isolation of the first superior and inferior branches was applied. RESULTS: All
      74 LCPVs were successfully isolated. A total of 64% patients (LCPV group) and 66%
      patients (control group) remained in sinus rhythm after mean follow-up of 1.9 +/-
      0.9 years (P = .820). In 18 of 26 patients (69%) with atrial tachyarrhythmia
      recurrence, a repeat procedure using radiofrequency energy was performed, and a
      total of 56% LCPVs were found to be persistently isolated (control group: 61% of
      left-sided PVs, P = .801). CONCLUSION: Patients with an LCPV undergoing CB2-based
      PVI demonstrate a high acute success rate. Comparable results with regard to
      clinical success and durability of PVI were shown when comparing patients of the
      LCPV group and the control group.

PMID- 28495654
TI  - Minimally invasive surgical ablation: Should we ablate harder or smarter?

PMID- 28495655
TI  - Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated
      increase in heart rate: Whole-heart study in a homozygous sodium/calcium
      exchanger overexpressor mouse model.
AB  - BACKGROUND: The cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to
      diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has
      been found in heart failure and atrial fibrillation. The influence of increased
      NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart
      rate, and cardiac conduction properties is unknown. OBJECTIVE: The purpose of
      this study was to investigate the influence of NCX overexpression in a homozygous
      transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function.
      METHODS: Langendorff-perfused, beating whole hearts of NCX-OE and the
      corresponding wild-type (WT) were studied +/- isoproterenol (ISO; 0.2 MUM).
      Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN
      WCL were obtained. RESULTS: At baseline, basal heart rate was unaltered between
      NCX-OE and WT (WT: cycle length [CL] 177.6 +/- 40.0 ms, no. of hearts [n] = 20;
      NCX-OE: CL 185.9 +/- 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE
      exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 +/- 13.4
      ms, n = 20; NCX-OE: CL 117.7 +/- 14.2 ms, n = 18; P <.001). ISO led to a
      significant shortening of the anterograde and retrograde AVN-WCL without
      differences between NCX-OE and WT. CONCLUSION: This study is the first to
      demonstrate that increased NCX activity enhances beta-adrenergic increase of
      heart rate. Mechanistically, increased NCX inward mode activity may promote
      acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus
      enhancing chronotropy in NCX-OE. These findings suggest a novel potential
      therapeutic target for heart rate control in the presence of increased NCX
      activity, such as heart failure.

PMID- 28495656
TI  - Dehydroepiandrosterone sulfate augments blood-brain barrier and tight junction
      protein expression in brain endothelial cells.
AB  - Tight junctions (TJ) between brain endothelial cells are essential for formation
      and maintenance of the blood-brain barrier (BBB). Although loss of BBB integrity
      is associated with several neuropathological disorders, treatments that augment
      or stabilise the BBB are scarce. Here we show that physiological concentrations
      of dehydroepiandrosterone sulfate (DHEAS) stimulate the expression of the TJ
      proteins zonula occludens-1 (ZO-1) and claudin-3 in the brain-derived endothelial
      cell line bEnd.3 and promote TJ formation between neighbouring cells,
      demonstrated by augmented transendothelial resistance across cell monolayers.
      Silencing androgen receptor expression by siRNA does not prevent DHEAS-induced
      stimulation of ZO-1 expression, indicating that conversion of DHEAS into
      testosterone is not required for its actions. Suppression of Gnalpha11 expression
      by siRNA prevents DHEAS actions, pointing towards a G-protein-coupled receptor as
      being a mediator of the DHEAS effects. These results are consistent with the idea
      that DHEAS, acting as a hormone in its own right, supports the integrity of the
      BBB. The current findings might help in developing new strategies for the
      prevention or treatment of neurological disorders associated with BBB defects.

PMID- 28495657
TI  - Outer membrane vesicles extracted from Neisseria meningitidis serogroup X for
      prevention of meningococcal disease in Africa.
AB  - Meningococcal disease is caused mainly by serogroups A, B, C, Y, W of N.
      meningitidis. However, numerous cases of meningitis caused by serogroup X N.
      meningitidis (MenX) have recently been reported in several African countries.
      Currently, there are no licensed vaccines against this pathogen and most of the
      MenX cases have been caused by meningococci from clonal complex (c.c) 181.
      Detergent extracted meningococcal outer membrane vesicle (dOMV) vaccines have
      previously shown to be safe and effective against epidemics of serogroup B
      meningococcal disease in all age groups. The aim of this work is therefore to
      obtain, characterize and evaluate the vaccine potential of dOMVs derived from a
      MenX strain (OMVx). Three experimental lots of OMVx were prepared by deoxycholate
      extraction from the MenX strain BF 2/97. Size and morphology of the vesicles was
      determined by Dynamic Light Scattering and electron microscopy, whereas the
      antigenic composition was characterized by gel electrophoresis and
      immunoblotting. OMVx were thereafter adsorbed to aluminium hydroxide (OMVx/AL)
      and two doses of OMVx were administered s.c. to groups of Balb/c mice three weeks
      apart. The immunogenicity and functional antibody activities in sera were
      evaluated by ELISA (anti-OMVx specific IgG responses) and serum bactericidal
      activity (SBA) assay. The size range of OMVx was shown to be between 90 and
      120nm, whereas some of the antigens detected were the outer membrane proteins
      PorA, OpcA and RmpM. The OMVx/AL elicited high anti-OMVx antibody responses with
      bactericidal activity and no bactericidal activity was observed in the control
      group of no immunised mice. The results demonstrate that OMVx are immunogenic and
      could form part of a future vaccine to prevent the majority of meningococcal
      disease in the African meningitis belt.

PMID- 28495658
TI  - Genomics of hypertension.
AB  - A complex network of interacting pathways involving renal, neural, endocrine,
      vascular and other mechanisms controls the main determinants of blood pressure -
      cardiac output and total peripheral resistance. Multiple genes within each of
      these systems contribute to the specialized functions regulating blood pressure.
      The monogenic forms of blood pressure dysregulation have provided valuable
      insights into blood pressure regulation and expanded our understanding of both
      the mechanisms and the treatment of hypertension. Genome wide association studies
      have identified over 100 single nucleotide polymorphisms associated with blood
      pressure phenotypes and have identified plausible novel pathways of BP regulation
      and putative drug targets.

PMID- 28495659
TI  - Social inclusion of individuals with intellectual disabilities in the military.
AB  - BACKGROUND: Despite policies advocating the social inclusion of persons with
      disabilities in all settings that are a part of everyday life within society,
      individuals with intellectual disabilities (ID) are usually excluded from service
      in the military. AIMS: This study examined the meaning of service in the military
      for individuals with ID from the perspective of various stakeholder groups.
      METHODS AND PROCEDURES: Semi-structured qualitative interviews were conducted
      with 31 individuals with ID, 36 relatives, and 28 commanders. The recent model
      for social inclusion developed by Simplican et al. (2015) served as the basis for
      analyses. OUTCOMES AND RESULTS: Findings suggest a successful social inclusion
      process for individuals with ID, which resulted in them feeling as an integral
      part and as contributing members of the military unit and of society at large.
      Social inclusion in the military was described with reference to two overlapping
      and interacting domains of interpersonal relationships and community
      participation. CONCLUSIONS AND IMPLICATIONS: The interaction between
      interpersonal relationships within the military and community participation has
      led to positive outcomes for soldiers with ID. Recommendations are provided for
      the continued inclusion of individuals with ID in the military and in other
      everyday settings.

PMID- 28495660
TI  - Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to
      Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in
      Older Inpatients: A Study Proposal.
AB  - BACKGROUND: Frail older people with multiple interacting conditions,
      polypharmacy, and complex care needs are particularly exposed to health care
      related adverse events. Among these, anticoagulant-related thromboembolic and
      hemorrhagic events are particularly frequent and serious in older inpatients. The
      growing use of anticoagulants in this population and their substantial risk of
      toxicity and inefficacy have therefore become an important patient safety and
      public health concern worldwide. Anticoagulant-related adverse events and the
      quality of anticoagulation management should thus be routinely assessed to
      improve patient safety in vulnerable older inpatients. OBJECTIVE: This project
      aims to develop and validate a set of outcome and process indicators based on
      linked administrative health data (ie, insurance claims data linked to hospital
      discharge data) assessing older inpatient safety related to anticoagulation in
      both Switzerland and France, and enabling comparisons across time and among
      hospitals, health territories, and countries. Geriatric patient safety indicators
      (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality
      indicators (GQIs) will evaluate the management of anticoagulants for the
      prevention and treatment of arterial or venous thromboembolism in older
      inpatients. METHODS: GPSIs will measure cumulative incidences of thromboembolic
      and bleeding adverse events based on hospital discharge data linked to insurance
      claims data. Using linked administrative health data will improve GPSI risk
      adjustment on patients' conditions that are present at admission and will capture
      in-hospital and postdischarge adverse events. GQIs will estimate the proportion
      of index hospital stays resulting in recommended anticoagulation at discharge and
      up to various time frames based on the same electronic health data. The GPSI and
      GQI development and validation process will comprise 6 stages: (1) selection and
      specification of candidate indicators, (2) definition of administrative data
      based algorithms, (3) empirical measurement of indicators using linked
      administrative health data, (4) validation of indicators, (5) analyses of
      geographic and temporal variations for reliable and valid indicators, and (6)
      data visualization. RESULTS: Study populations will consist of 166,670 Swiss and
      5,902,037 French residents aged 65 years and older admitted to an acute care
      hospital at least once during the 2012-2014 period and insured for at least 1
      year before admission and 1 year after discharge. We will extract Swiss data from
      the Helsana Group data warehouse and French data from the national health
      insurance information system (SNIIR-AM). The study has been approved by Swiss and
      French ethics committees and regulatory organizations for data protection.
      CONCLUSIONS: Validated GPSIs and GQIs should help support and drive quality and
      safety improvement in older inpatients, inform health care stakeholders, and
      enable international comparisons. We discuss several limitations relating to the
      representativeness of study populations, accuracy of administrative health data,
      methods used for GPSI criterion validity assessment, and potential confounding
      bias in comparisons based on GQIs, and we address these limitations to strengthen
      study feasibility and validity.

PMID- 28495661
TI  - Virtual Reality as an Adjunct Home Therapy in Chronic Pain Management: An
      Exploratory Study.
AB  - BACKGROUND: Virtual reality (VR) therapy has been successfully used as an adjunct
      therapy for the management of acute pain in adults and children, and evidence of
      potential efficacy in other health applications is growing. However, minimal
      research exists on the value of VR as an intervention for chronic pain.
      OBJECTIVE: This case series examined the value of VR to be used as an adjunctive
      therapy for chronic pain patients in their own homes. METHODS: An exploratory
      approach using a case series and personal interviews was used. Ten chronic pain
      patients received VR therapy for 30 min on alternate days for 1 month. Pre- and
      postexposure (immediately afterwards, 3 h, and at 24 h) pain assessment was
      recorded using the Numerical Rating Scale (NRS), and weekly using the Brief Pain
      Inventory (BPI) and Self-completed Leeds Assessment of Neuropathic Symptoms and
      Signs pain scale (S-LANSS). Terminal semistructured personal interviews with the
      patients were also undertaken. RESULTS: Of the 8 patients who completed the
      study, 5 of them reported that pain was reduced during the VR experience but no
      overall treatment difference in pain scores postexposure was observed. VR was not
      associated with any serious adverse events, although 60% of patients reported
      some cybersickness during some of the experiences. CONCLUSIONS: Of note is that
      the majority of these study participants reported a reduction in pain while using
      the VR but with highly individualized responses. One patient also reported some
      short-term improved mobility following VR use. Some evidence was found for the
      short-term efficacy of VR in chronic pain but no evidence for persistent
      benefits.

PMID- 28495663
TI  - Brexit is bad for health, and doctors should say so.

PMID- 28495664
TI  - What do NHS doctors think about their work?

PMID- 28495662
TI  - The Development, Validation, and User Evaluation of Foodbook24: A Web-Based
      Dietary Assessment Tool Developed for the Irish Adult Population.
AB  - BACKGROUND: The application of technology in the area of dietary assessment has
      resulted in the development of an array of tools, which are often specifically
      designed for a particular country or region. OBJECTIVE: The aim of this study was
      to describe the development, validation, and user evaluation of a Web-based
      dietary assessment tool "Foodbook24." METHODS: Foodbook24 is a Web-based, dietary
      assessment tool consisting of a 24-hour dietary recall (24HDR) and food frequency
      questionnaire (FFQ) alongside supplementary questionnaires. Validity of the 24HDR
      component was assessed by 40 participants, who completed 3 nonconsecutive, self
      administered 24HDR using Foodbook24 and a 4-day semi-weighed food diary at
      separate time points. Participants also provided fasted blood samples and 24-hour
      urine collections for the identification of biomarkers of nutrient and food group
      intake during each recording period. Statistical analyses on the nutrient and
      food group intake data derived from each method were performed in SPSS version
      20.0 (SPSS Inc). Mean nutrient intakes (and standard deviations) recorded using
      each method of dietary assessment were calculated. Spearman and Pearson
      correlations, Wilcoxon Signed Rank and Paired t test were used to investigate the
      agreement and differences between the nutritional output from Foodbook24 (test
      method) and the 4-day semi-weighed food diary (reference method). Urinary and
      plasma biomarkers of nutrient intake were used as an objective validation of
      Foodbook24. To investigate the user acceptability of Foodbook24, participants
      from different studies involved with Foodbook24 were asked to complete an
      evaluation questionnaire. RESULTS: For nutrient intake, correlations between the
      dietary assessment methods were acceptable to very good in strength and
      statistically significant (range r=.32 to .75). There were some significant
      differences between reported mean intakes of micronutrients recorded by both
      methods; however, with the exception of protein (P=.03), there were no
      significant differences in the reporting of energy or macronutrient intake. Of
      the 19 food groups investigated in this analysis, there were significant
      differences between 6 food groups reported by both methods. Spearman correlations
      for biomarkers of nutrient and food group intake and reported intake were similar
      for both methods. A total of 118 participants evaluated the acceptability of
      Foodbook24. The tool was well-received and the majority, 67.8% (80/118), opted
      for Foodbook24 as the preferred method for future dietary intake assessment when
      compared against a traditional interviewer led recall and semi-weighed food
      diary. CONCLUSIONS: The results of this study demonstrate the validity and user
      acceptability of Foodbook24. The results also highlight the potential of
      Foodbook24, a Web-based dietary assessment method, and present a viable
      alternative to nutritional surveillance in Ireland.

PMID- 28495665
TI  - General anaesthesia under the age of 4 years has minimal impact on future
      academic performance.

PMID- 28495666
TI  - How to use nasal nitric oxide in a child with suspected primary ciliary
      dyskinesia.
AB  - Measuring nasal nitric oxide (nNO) is increasingly used as part of testing for
      primary ciliary dyskinesia (PCD). The diagnosis of PCD is often delayed until
      after bronchiectasis is established and auditory damage has occurred. It is
      important that all paediatricians are aware of clinical features that are
      suggestive of PCD that should prompt diagnostic testing. nNO levels are
      recognised to be low in people with PCD and results generated by static
      chemiluminescence analysers using velum closure technique in older children have
      good sensitivity and specificity. However, to conclusively rule PCD in or out,
      further tests of ciliary function are required and assessment of cilia
      ultrastructure, immunohistochemistry studies and genotyping may also be
      indicated. These tests are more complex, invasive and expensive than nNO. nNO is
      less well studied in younger children where tidal breathing measurements are
      required. Portable nitric oxide analysers are also increasingly used in practice.
      This paper discusses when to consider PCD as a possible diagnosis in a child
      along with the indications, physiological and technical background and clinical
      utility of nNO as a test for PCD in children.

PMID- 28495667
TI  - Fifteen-minute consultation in the normal child: Challenges relating to sexuality
      and gender identity in children and young people.
AB  - Lesbian, gay, bisexual and transgender (LGBT+) young people face several
      challenges in their daily lives, including specific healthcare inequalities.
      Negative societal attitudes towards sexual and gender minorities, and the effects
      of regular experiences of bullying and homophobia/transphobia exacerbate the
      normal trials and tribulations of childhood and adolescence. Barriers to
      accessing healthy activities, such as sport, are created by perceived stigma and
      real-life experiences. Healthcare environments are by default heteronormative and
      contribute to the isolation and exclusion of LGBT+ young people. Paediatricians
      are well placed to act on these healthcare inequalities and to advocate for LGBT+
      youth, through simple changes to individual practice as well as system-wide
      improvements.

PMID- 28495668
TI  - Price cap could mean patients miss out on newest stents, cardiologists warn.

PMID- 28495670
TI  - Do rapid diagnostic tests improve overall quality of care?

PMID- 28495671
TI  - Waiting times at their "worst," but quality of care holds up.

PMID- 28495672
TI  - Elevated serum levels of sonic hedgehog are associated with fibrotic and vascular
      manifestations in systemic sclerosis.

PMID- 28495673
TI  - Parallel imaging of Drosophila embryos for quantitative analysis of genetic
      perturbations of the Ras pathway.
AB  - The Ras pathway patterns the poles of the Drosophila embryo by downregulating the
      levels and activity of a DNA-binding transcriptional repressor Capicua (Cic). We
      demonstrate that the spatiotemporal pattern of Cic during this signaling event
      can be harnessed for functional studies of mutations in the Ras pathway in human
      diseases. Our approach relies on a new microfluidic device that enables parallel
      imaging of Cic dynamics in dozens of live embryos. We found that although the
      pattern of Cic in early embryos is complex, it can be accurately approximated by
      a product of one spatial profile and one time-dependent amplitude. Analysis of
      these functions of space and time alone reveals the differential effects of
      mutations within the Ras pathway. Given the highly conserved nature of Ras
      dependent control of Cic, our approach provides new opportunities for functional
      analysis of multiple sequence variants from developmental abnormalities and
      cancers.

PMID- 28495674
TI  - Noncentral Nervous System Systemic Embolism in Patients With Atrial Fibrillation:
      Results From ROCKET AF (Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition
      Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in
      Atrial Fibrillation).

PMID- 28495675
TI  - High-Value Home Health Care for Patients With Heart Failure: An Opportunity to
      Optimize Transitions From Hospital to Home.

PMID- 28495676
TI  - The Review and Editorial Process at Circulation: Cardiovascular Quality and
      Outcomes: The Worst System, Except for All the Others.

PMID- 28495677
TI  - High-throughput and site-specific identification of 2'-O-methylation sites using
      ribose oxidation sequencing (RibOxi-seq).
AB  - Ribose methylation (2'-O-methylation, 2'-OMe) occurs at high frequencies in rRNAs
      and other small RNAs and is carried out using a shared mechanism across
      eukaryotes and archaea. As RNA modifications are important for ribosome
      maturation, and alterations in these modifications are associated with cellular
      defects and diseases, it is important to characterize the landscape of 2'-O
      methylation. Here we report the development of a highly sensitive and accurate
      method for ribose methylation detection using next-generation sequencing. A key
      feature of this method is the generation of RNA fragments with random 3'-ends,
      followed by periodate oxidation of all molecules terminating in 2',3'-OH groups.
      This allows only RNAs harboring 2'-OMe groups at their 3'-ends to be sequenced.
      Although currently requiring microgram amounts of starting material, this method
      is robust for the analysis of rRNAs even at low sequencing depth.

PMID- 28495678
TI  - Sphingolipid metabolic flow controls phosphoinositide turnover at the trans-Golgi
      network.
AB  - Sphingolipids are membrane lipids globally required for eukaryotic life. The
      sphingolipid content varies among endomembranes with pre- and post-Golgi
      compartments being poor and rich in sphingolipids, respectively. Due to this
      different sphingolipid content, pre- and post-Golgi membranes serve different
      cellular functions. The basis for maintaining distinct subcellular sphingolipid
      levels in the presence of membrane trafficking and metabolic fluxes is only
      partially understood. Here, we describe a homeostatic regulatory circuit that
      controls sphingolipid levels at the trans-Golgi network (TGN). Specifically, we
      show that sphingomyelin production at the TGN triggers a signalling pathway
      leading to PtdIns(4)P dephosphorylation. Since PtdIns(4)P is required for
      cholesterol and sphingolipid transport to the trans-Golgi network, PtdIns(4)P
      consumption interrupts this transport in response to excessive sphingomyelin
      production. Based on this evidence, we envisage a model where this homeostatic
      circuit maintains a constant lipid composition in the trans-Golgi network and
      post-Golgi compartments, thus counteracting fluctuations in the sphingolipid
      biosynthetic flow.

PMID- 28495679
TI  - Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER
      subdomains.
AB  - The autophagosome, a double-membrane structure mediating degradation of
      cytoplasmic materials by macroautophagy, is formed in close proximity to the
      endoplasmic reticulum (ER). However, how the ER membrane is involved in autophagy
      initiation and to which membrane structures the autophagy-initiation complex is
      localized have not been fully characterized. Here, we were able to biochemically
      analyze autophagic intermediate membranes and show that the autophagy-initiation
      complex containing ULK and FIP200 first associates with the ER membrane. To
      further characterize the ER subdomain, we screened phospholipid biosynthetic
      enzymes and found that the autophagy-initiation complex localizes to
      phosphatidylinositol synthase (PIS)-enriched ER subdomains. Then, the initiation
      complex translocates to the ATG9A-positive autophagosome precursors in a PI3P
      dependent manner. Depletion of phosphatidylinositol (PI) by targeting bacterial
      PI-specific phospholipase C to the PIS domain impairs recruitment of downstream
      autophagy factors and autophagosome formation. These findings suggest that the
      autophagy-initiation complex, the PIS-enriched ER subdomain, and ATG9A vesicles
      together initiate autophagosome formation.

PMID- 28495680
TI  - DNA-binding determinants and cellular thresholds for human telomerase repeat
      addition processivity.
AB  - The reverse transcriptase telomerase adds telomeric repeats to chromosome ends.
      Purified human telomerase catalyzes processive repeat synthesis, which could
      restore the full ~100 nucleotides of (T2AG3)n lost from replicated chromosome
      ends as a single elongation event. Processivity inhibition is proposed to be a
      basis of human disease, but the impacts of different levels of processivity on
      telomere maintenance have not been examined. Here, we delineate side chains in
      the telomerase active-site cavity important for repeat addition processivity,
      determine how they contribute to duplex and single-stranded DNA handling, and
      test the cellular consequences of partial or complete loss of repeat addition
      processivity for telomere maintenance. Biochemical findings oblige a new model
      for DNA and RNA handling dynamics in processive repeat synthesis. Biological
      analyses implicate repeat addition processivity as essential for telomerase
      function. However, telomeres can be maintained by telomerases with lower than
      wild-type processivity. Furthermore, telomerases with low processivity
      dramatically elongate telomeres when overexpressed. These studies reveal distinct
      consequences of changes in telomerase repeat addition processivity and expression
      level on telomere elongation and length maintenance.

PMID- 28495682
TI  - A recurring theme in pulmonary fibrosis genetics.

PMID- 28495681
TI  - A comparative analysis of costs of single and dual rapid HIV and syphilis
      diagnostics: results from a randomised controlled trial in Colombia.
AB  - BACKGROUND: HIV and congenital syphilis are major public health burdens
      contributing to substantial perinatal morbidity and mortality globally. Although
      studies have reported on the costs and cost-effectiveness of rapid diagnostic
      tests (RDTs) for syphilis screening within antenatal care in a number of resource
      constrained settings, empirical evidence on country-specific cost and estimates
      of single RDTs compared with dual RDTs for HIV and syphilis are limited. METHODS:
      A cluster randomised controlled study design was used to compare the incremental
      costs of two testing algorithms: (1) single RDTs for HIV and syphilis and (2)
      dual RDTs for HIV and syphilis, in 12 health facilities in Bogota and Cali,
      Colombia. The costs of single HIV and syphilis RDTs and dual HIV and syphilis
      RDTs were collected from each of the health facilities. The economic costs per
      woman tested for HIV and syphilis and costs per woman treated for syphilis
      defined as the total costs required to test and treat one woman for syphilis were
      estimated. RESULTS: A total of 2214 women were tested in the study facilities.
      Cost per pregnant woman tested and cost per woman treated for syphilis were
      US$10.26 and US$607.99, respectively in the single RDT arm. For the dual RDTs,
      the cost per pregnant woman tested for HIV and syphilis and cost per woman
      treated for syphilis were US$15.89 and US$1859.26, respectively. Overall costs
      per woman tested for HIV and syphilis and cost per woman treated for syphilis
      were lower in Cali compared with Bogota across both intervention arms. Staff
      costs accounted for the largest proportion of costs while treatment costs
      comprised <1% of the preventive programme. CONCLUSIONS: Findings show lower
      average costs for single RDTs compared with dual RDTs with costs sensitive to
      personnel costs and the scale of output at the health facilities. TRIAL
      REGISTRATION NUMBER: NCT02454816; results.

PMID- 28495683
TI  - Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase
      mutations.

PMID- 28495684
TI  - The Art of Breathing: Pranayama.

PMID- 28495685
TI  - "Characterisation of patients with interstitial pneumonia with autoimmune
      features." Justin M. Oldham, Ayodeji Adegunsoye, Eleanor Valenzi, Cathryn Lee,
      Leah Witt, Lena Chen, Aliya N. Husain, Steven Montner, Jonathan H. Chung, Vincent
      Cottin, Aryeh Fischer, Imre Noth, Rekha Vij and Mary E. Strek. Eur Respir J 2016;
      47: 1767-1775.

PMID- 28495686
TI  - Incidence of non-pulmonary cancer and lung cancer by amount of emphysema and
      airway wall thickness: a community-based cohort.
AB  - There is limited knowledge about the prognostic value of quantitative computed
      tomography (CT) measures of emphysema and airway wall thickness in cancer.The aim
      of this study was to investigate if using CT to quantitatively assess the amount
      of emphysema and airway wall thickness independently predicts the subsequent
      incidence of non-pulmonary cancer and lung cancer.In the GenKOLS study of 2003
      2005, 947 ever-smokers performed spirometry and underwent CT examination. The
      main predictors were the amount of emphysema measured by the percentage of low
      attenuation areas (%LAA) on CT and standardised measures of airway wall thickness
      (AWT-PI10). Cancer data from 2003-2013 were obtained from the Norwegian Cancer
      Register. The hazard ratio associated with emphysema and airway wall thickness
      was assessed using Cox proportional hazards regression for cancer
      diagnoses.During 10 years of follow-up, non-pulmonary cancer was diagnosed in 11%
      of the subjects with LAA <3%, in 19% of subjects with LAA 3-10%, and in 17% of
      subjects with LAA >=10%. Corresponding numbers for lung cancer were 2%, 3% and
      11%, respectively. After adjustment, the baseline amount of emphysema remained a
      significant predictor of the incidence of non-pulmonary cancer and lung cancer.
      Airway wall thickness did not predict cancer independently.This study offers a
      strong argument that emphysema is an independent risk factor for both non
      pulmonary cancer and lung cancer.

PMID- 28495687
TI  - Phenotypes of COPD patients with a smoking history in Central and Eastern Europe:
      the POPE Study.
AB  - Chronic obstructive pulmonary disease (COPD) represents a major health problem in
      Central and Eastern European (CEE) countries; however, there are no data
      regarding clinical phenotypes of these patients in this region.Participation in
      the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to
      stable patients with COPD in a real-life setting. The primary aim of this study
      was to assess the prevalence of phenotypes according to predefined criteria.
      Secondary aims included analysis of differences in symptom load, comorbidities
      and pharmacological treatment.3362 patients with COPD were recruited in 10 CEE
      countries. 63% of the population were nonexacerbators, 20.4% frequent
      exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic
      bronchitis and 6.9% were classified as asthma-COPD overlap. Differences in the
      distribution of phenotypes between countries were observed, with the highest
      heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity
      observed in the asthma-COPD cohort. There were statistically significant
      differences in symptom load, lung function, comorbidities and treatment between
      these phenotypes.The majority of patients with stable COPD in CEE are
      nonexacerbators; however, there are distinct differences in surrogates of disease
      severity and therapy between predefined COPD phenotypes.

PMID- 28495689
TI  - Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase
      mutations.

PMID- 28495688
TI  - The development and validation of the Bronchiectasis Health Questionnaire.
AB  - Health-related quality of life or health status is significantly impaired in
      bronchiectasis. There is a paucity of brief, simple-to-use, disease-specific
      health status measures. The aim of this study was to develop and validate the
      Bronchiectasis Health Questionnaire (BHQ), a new health status measure that is
      brief and generates a single overall score.Patients with bronchiectasis were
      recruited from two outpatient clinics, during a clinically stable stage. The
      development of the questionnaire followed three phases: item generation and item
      reduction using Rasch analysis, validation, and repeatability testing. The BHQ
      was translated into 11 languages using standardised methodology.206 patients with
      bronchiectasis completed a preliminary 65-item questionnaire. 55 items were
      removed due to redundancy or poor fit to the Rasch model. The final version of
      the BHQ consisted of 10 items. Internal consistency was good (Cronbach's
      alpha=0.85). Convergent validity of the BHQ with the St George's Respiratory
      Questionnaire was high (r= -0.82; p<0.001) and moderate with lung function
      (forced expiratory volume in 1 s % predicted r= -0.27; p=0.001). There was a
      significant association between BHQ scores and number of exacerbations of
      bronchiectasis in the last 12 months (p<0.001), hospital admissions (p=0.001) and
      computed tomography scan bronchiectasis pulmonary lobe counts (p<0.001). BHQ
      scores were significantly worse in patients with sputum bacterial colonisation
      versus no colonisation (p=0.048). The BHQ was highly repeatable after 2 weeks
      (intraclass correlation coefficient 0.89).The BHQ is a brief, valid and
      repeatable, self-completed health status questionnaire for bronchiectasis that
      generates a single total score. It can be used in the clinic to assess
      bronchiectasis from the patient's perspective.

PMID- 28495690
TI  - Intensive care in thoracic oncology.
AB  - The admission of lung cancer patients to intensive care is related to
      postprocedural/postoperative care and medical complications due to cancer or its
      treatment, but is also related to acute organ failure not directly related to
      cancer.Despite careful preoperative risk management and the use of modern
      surgical and anaesthetic techniques, thoracic surgery remains associated with
      high morbidity, related to the extent of resection and specific comorbidities.
      Fast-tracking processes with timely recognition and treatment of complications
      favourably influence patient outcome. Postoperative preventive and therapeutic
      management has to be carefully planned in order to reduce postoperative morbidity
      and mortality.For patients with severe complications, intensive care unit (ICU)
      mortality rate ranges from 13% to 47%, and hospital mortality ranges from 24% to
      65%. Common predictors of in-hospital mortality are severity scores, number of
      failing organs, general condition, respiratory distress and the need for
      mechanical ventilation or vasopressors. When considering long-term survival after
      discharge, cancer-related parameters retain their prognostic value.Thoracic
      surgeons, anesthesiologists, pneumologists, intensivists and oncologists need to
      develop close and confident partnerships aimed at implementing evidence-based
      patient care, securing clinical pathways for patient management while promoting
      education, research and innovation. The final decision on admitting a patient
      with lung to the ICU should be taken in close partnership between this medical
      team and the patient and his or her relatives.

PMID- 28495691
TI  - Screening for pulmonary arterial hypertension in an unselected prospective
      systemic sclerosis cohort.
AB  - Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc)
      improves outcomes. The DETECT screening algorithm is recommended in a high-risk
      SSc subgroup. This study aims to compare prospectively the positive predictive
      value of screening using the DETECT algorithm and the 2009 European Society of
      Cardiology/European Respiratory Society (ESC/ERS) guidelines, and to compare
      their cost-effectiveness in an unselected, day-to-day SSc population. Post hoc,
      screening according to the 2015 ESC/ERS guidelines using echocardiographic
      parameters alone ("2015 echo screening") or combined with the DETECT algorithm
      ("2015 combined screening") in high-risk subjects was analysed.195 consecutive
      SSc patients included in the Ghent University Hospital SSc cohort were screened
      using different algorithms.The referral rate for right heart catheterisation was
      32% (63 out of 195 patients) (46/4/13/34/40 patients using the DETECT
      algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening).
      Right heart catheterisation was performed in 53 patients (84%) (36 (78%)/four
      (100%)/13 (100%)/28 (82%)/32 (80%) patients recommended by the DETECT
      algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). PAH
      was diagnosed in three patients (incidence 1.5%.year-1, 95% CI 0.5-4.4), in whom
      all algorithms recommended a right heart catheterisation. The positive predictive
      value was 6% (95% CI 2-17%; three out of 49 patients) for the DETECT algorithm,
      18% (95% CI 6-41%; three out of 17 patients) for the 2009 guidelines, 23% (95% CI
      8-50%; three out of 13 patients) for both, 11% (95% CI 4-27%; three out of 28
      patients) for the 2015 echo screening and 9% (95% CI 3-24%; three out of 32
      patients) for the 2015 combined screening. The cost was EUR224/80/90/112 per
      patient using the DETECT algorithm/2009 guidelines/2015 echo screening/2015
      combined screening.Echocardiography may remain a candidate first step for PAH
      screening in SSc.

PMID- 28495693
TI  - Tropical Australia is a potential reservoir of non-tuberculous mycobacteria in
      cystic fibrosis.

PMID- 28495694
TI  - Phenotypes contribute to treatments.

PMID- 28495692
TI  - Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease
      and familial pulmonary fibrosis.
AB  - Despite its high prevalence and mortality, little is known about the pathogenesis
      of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that
      familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern
      of interstitial pneumonia and common environmental risk factors, we hypothesised
      that the two diseases might share additional risk factors, including FPF-linked
      genes. Our aim was to identify coding mutations of FPF-risk genes associated with
      RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a
      discrete number of FPF-linked genes and performed a burden test to assess the
      excess number of mutations in RA-ILD patients compared to controls.Among the 101
      RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations
      in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA
      ILD patients and 1010 controls of European ancestry, revealed an excess of TERT,
      RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12;
      p=9.45*10-4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or
      PARN mutation than in controls (p=2.87*10-2).Our results support the contribution
      of FPF-linked genes to RA-ILD susceptibility.

PMID- 28495695
TI  - Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency
      associated pulmonary alveolar proteinosis and fibrosis.

PMID- 28495696
TI  - Health-related quality of life questionnaires in bronchiectasis: the simplest way
      to quantify complexity.

PMID- 28495697
TI  - Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency
      associated pulmonary alveolar proteinosis and fibrosis.

PMID- 28495698
TI  - Pulmonary arterial hypertension: screening challenges in systemic sclerosis and
      future directions.

PMID- 28495699
TI  - American College of Cardiology/American Heart Association (ACC/AHA) Class I
      Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic
      Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From
      the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
AB  - BACKGROUND: The prevalence estimates of statin eligibility among Hispanic/Latinos
      living in the United States under the new 2013 American College of
      Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines
      are not known. METHODS AND RESULTS: We estimated prevalence of statin eligibility
      under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment
      Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of
      Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights
      calibrated to the 2010 US census. We examined the characteristics of
      Hispanic/Latinos treated and not treated with statins under both guidelines. We
      also redetermined the statin-therapy eligibility by using black risk estimates
      for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with
      NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0
      16.7%) to 26.9% (95% CI 25.7-28.0%) under the 2013 ACC/AHA guidelines. This was
      mainly driven by the >=7.5% atherosclerotic cardiovascular disease risk criteria
      (prevalence 13.9% [95% CI 13.0-14.7%]). Of the participants eligible for statin
      eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3
      30.0%) and 20.6% (95% CI 19.4-21.9%) were taking statins, respectively. Statin
      eligible participants who were not taking statins had a higher prevalence of
      cardiovascular risk factors compared with statin-eligible participants who were
      taking statins. There was no significant increase in statin eligibility when
      atherosclerotic cardiovascular disease risk was calculated by using black
      estimates instead of recommended white estimates (increase by 1.4%, P=0.12) for
      Hispanic/Latinos. CONCLUSIONS: The eligibility of statin therapy increased
      consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA
      guidelines and therefore will potentially increase the number of undertreated
      Hispanic/Latinos in the United States.

PMID- 28495700
TI  - Visualizing dynamic microvillar search and stabilization during ligand detection
      by T cells.
AB  - During immune surveillance, T cells survey the surface of antigen-presenting
      cells. In searching for peptide-loaded major histocompatibility complexes
      (pMHCs), they must solve a classic trade-off between speed and sensitivity. It
      has long been supposed that microvilli on T cells act as sensory organs to enable
      search, but their strategy has been unknown. We used lattice light-sheet and
      quantum dot-enabled synaptic contact mapping microscopy to show that anomalous
      diffusion and fractal organization of microvilli survey the majority of opposing
      surfaces within 1 minute. Individual dwell times were long enough to discriminate
      pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized
      microvilli. Stabilization was independent of tyrosine kinase signaling and the
      actin cytoskeleton, suggesting selection for avid TCR microclusters. This work
      defines the efficient cellular search process against which ligand detection
      takes place.

PMID- 28495703
TI  - News at a glance.

PMID- 28495702
TI  - Academia under fire in Hungary.

PMID- 28495701
TI  - Poor human olfaction is a 19th-century myth.
AB  - It is commonly believed that humans have a poor sense of smell compared to other
      mammalian species. However, this idea derives not from empirical studies of human
      olfaction but from a famous 19th-century anatomist's hypothesis that the
      evolution of human free will required a reduction in the proportional size of the
      brain's olfactory bulb. The human olfactory bulb is actually quite large in
      absolute terms and contains a similar number of neurons to that of other mammals.
      Moreover, humans have excellent olfactory abilities. We can detect and
      discriminate an extraordinary range of odors, we are more sensitive than rodents
      and dogs for some odors, we are capable of tracking odor trails, and our
      behavioral and affective states are influenced by our sense of smell.

PMID- 28495704
TI  - Pinpointing HIV spread in Africa poses risks.

PMID- 28495705
TI  - Who will watch the Amazon?

PMID- 28495706
TI  - In a first, natural selection defeats a biocontrol insect.

PMID- 28495707
TI  - Newest member of human family is surprisingly young.

PMID- 28495708
TI  - Pocket-sized sequencers start to pay off big.

PMID- 28495709
TI  - China cracks down on coastal fisheries.

PMID- 28495710
TI  - NIH to cap grants for well-funded investigators.

PMID- 28495711
TI  - Fears of Ebola resurgence quickly dispelled in Liberia.

PMID- 28495712
TI  - Where have all the insects gone?

PMID- 28495713
TI  - Saying goodbye to glaciers.

PMID- 28495714
TI  - Charge delivery goes the distance.

PMID- 28495715
TI  - Coupling and sharing when life is hard.

PMID- 28495716
TI  - Keeping in touch with the ER network.

PMID- 28495718
TI  - Biodefense in the 21st century.

PMID- 28495717
TI  - Myriad take two: Can genomic databases remain secret?

PMID- 28495719
TI  - Faulty logic.

PMID- 28495721
TI  - Tracing our ancestors in cave sediments.

PMID- 28495720
TI  - Why science? Scientists share their stories.

PMID- 28495722
TI  - Personalized printing for human health.

PMID- 28495723
TI  - Shipping iron around in small packages.

PMID- 28495724
TI  - Intricacy anchored by uranium.

PMID- 28495725
TI  - How much water is in that exoplanet?

PMID- 28495726
TI  - Resolution achieved.

PMID- 28495727
TI  - ER-PM contacts in nonclathrin endocytosis.

PMID- 28495729
TI  - Cancer immunotherapy according to GARP.

PMID- 28495728
TI  - Mapping the world's dry forests.

PMID- 28495731
TI  - Search and capture in space and time.

PMID- 28495730
TI  - Humans have a good sense of smell.

PMID- 28495732
TI  - As with donuts, the holes matter.

PMID- 28495733
TI  - Maximizing growth by sharing.

PMID- 28495734
TI  - Toward a world without glaciers.

PMID- 28495735
TI  - A more pathological amyloid-beta oligomer.

PMID- 28495737
TI  - Disrupting housefly gene reverses sex.

PMID- 28495736
TI  - Tug of war with anti-PD-1.

PMID- 28495739
TI  - Targeting senescence to combat osteoarthritis.

PMID- 28495738
TI  - Macrophages feel the heart beat.

PMID- 28495740
TI  - Crop resistance to parasites.

PMID- 28495742
TI  - Quantum dots visibly forge carbon bonds.

PMID- 28495741
TI  - An elusive magnet in an atomic cloud.

PMID- 28495743
TI  - A probable dwarf planet beyond Neptune.

PMID- 28495744
TI  - Selection acts on the neighbors.

PMID- 28495745
TI  - Three-dimensional holey-graphene/niobia composite architectures for ultrahigh
      rate energy storage.
AB  - Nanostructured materials have shown extraordinary promise for electrochemical
      energy storage but are usually limited to electrodes with rather low mass loading
      (~1 milligram per square centimeter) because of the increasing ion diffusion
      limitations in thicker electrodes. We report the design of a three-dimensional
      (3D) holey-graphene/niobia (Nb2O5) composite for ultrahigh-rate energy storage at
      practical levels of mass loading (>10 milligrams per square centimeter). The
      highly interconnected graphene network in the 3D architecture provides excellent
      electron transport properties, and its hierarchical porous structure facilitates
      rapid ion transport. By systematically tailoring the porosity in the holey
      graphene backbone, charge transport in the composite architecture is optimized to
      deliver high areal capacity and high-rate capability at high mass loading, which
      represents a critical step forward toward practical applications.

PMID- 28495748
TI  - HAT-P-26b: A Neptune-mass exoplanet with a well-constrained heavy element
      abundance.
AB  - A correlation between giant-planet mass and atmospheric heavy elemental abundance
      was first noted in the past century from observations of planets in our own Solar
      System and has served as a cornerstone of planet-formation theory. Using data
      from the Hubble and Spitzer Space Telescopes from 0.5 to 5 micrometers, we
      conducted a detailed atmospheric study of the transiting Neptune-mass exoplanet
      HAT-P-26b. We detected prominent H2O absorption bands with a maximum base-to-peak
      amplitude of 525 parts per million in the transmission spectrum. Using the water
      abundance as a proxy for metallicity, we measured HAT-P-26b's atmospheric heavy
      element content ([Formula: see text] times solar). This likely indicates that HAT
      P-26b's atmosphere is primordial and obtained its gaseous envelope late in its
      disk lifetime, with little contamination from metal-rich planetesimals.

PMID- 28495747
TI  - Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis.
AB  - The integration of endocytic routes is critical to regulate receptor signaling. A
      nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor
      (EGFR) is activated at high ligand concentrations and targets receptors to
      degradation, attenuating signaling. Here we performed an unbiased molecular
      characterization of EGFR-NCE. We identified NCE-specific regulators, including
      the endoplasmic reticulum (ER)-resident protein reticulon 3 (RTN3) and a specific
      cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of
      plasma membrane (PM)-ER contact sites that were required for the formation and/or
      maturation of NCE invaginations. Ca2+ release at these sites, triggered by
      inositol 1,4,5-trisphosphate (IP3)-dependent activation of ER Ca2+ channels, was
      needed for the completion of EGFR internalization. Thus, we identified a
      mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca2+
      signaling.

PMID- 28495749
TI  - Holliday junction resolvases mediate chloroplast nucleoid segregation.
AB  - Holliday junctions, four-stranded DNA structures formed during homologous
      recombination, are disentangled by resolvases that have been found in prokaryotes
      and eukaryotes but not in plant organelles. Here, we identify monokaryotic
      chloroplast 1 (MOC1) as a Holliday junction resolvase in chloroplasts by
      analyzing a green alga Chlamydomonas reinhardtii mutant defective in chloroplast
      nucleoid (DNA-protein complex) segregation. MOC1 is structurally similar to a
      bacterial Holliday junction resolvase, resistance to ultraviolet (Ruv) C, and
      genetically conserved among green plants. Reduced or no expression of MOC1 in
      Arabidopsis thaliana leads to growth defects and aberrant chloroplast nucleoid
      segregation. In vitro biochemical analysis and high-speed atomic force
      microscopic analysis revealed that A. thaliana MOC 1 (AtMOC1) binds and cleaves
      the core of Holliday junctions symmetrically. MOC1 may mediate chloroplast
      nucleoid segregation in green plants by resolving Holliday junctions.

PMID- 28495746
TI  - Restored iron transport by a small molecule promotes absorption and
      hemoglobinization in animals.
AB  - Multiple human diseases ensue from a hereditary or acquired deficiency of iron
      transporting protein function that diminishes transmembrane iron flux in distinct
      sites and directions. Because other iron-transport proteins remain active, labile
      iron gradients build up across the corresponding protein-deficient membranes.
      Here we report that a small-molecule natural product, hinokitiol, can harness
      such gradients to restore iron transport into, within, and/or out of cells. The
      same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin
      deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient
      zebrafish. These findings illuminate a general mechanistic framework for small
      molecule-mediated site- and direction-selective restoration of iron transport.
      They also suggest that small molecules that partially mimic the function of
      missing protein transporters of iron, and possibly other ions, may have potential
      in treating human diseases.

PMID- 28495753
TI  - Lucking into science.

PMID- 28495750
TI  - The extent of forest in dryland biomes.
AB  - Dryland biomes cover two-fifths of Earth's land surface, but their forest area is
      poorly known. Here, we report an estimate of global forest extent in dryland
      biomes, based on analyzing more than 210,000 0.5-hectare sample plots through a
      photo-interpretation approach using large databases of satellite imagery at (i)
      very high spatial resolution and (ii) very high temporal resolution, which are
      available through the Google Earth platform. We show that in 2015, 1327 million
      hectares of drylands had more than 10% tree-cover, and 1079 million hectares
      comprised forest. Our estimate is 40 to 47% higher than previous estimates,
      corresponding to 467 million hectares of forest that have never been reported
      before. This increases current estimates of global forest cover by at least 9%.

PMID- 28495751
TI  - Male sex in houseflies is determined by Mdmd, a paralog of the generic splice
      factor gene CWC22.
AB  - Across species, animals have diverse sex determination pathways, each consisting
      of a hierarchical cascade of genes and its associated regulatory mechanism.
      Houseflies have a distinctive polymorphic sex determination system in which a
      dominant male determiner, the M-factor, can reside on any of the chromosomes. We
      identified a gene, Musca domesticamale determiner (Mdmd), as the M-factor. Mdmd
      originated from a duplication of the spliceosomal factor gene CWC22
      (nucampholin). Targeted Mdmd disruption results in complete sex reversal to
      fertile females because of a shift from male to female expression of the
      downstream genes transformer and doublesex The presence of Mdmd on different
      chromosomes indicates that Mdmd translocated to different genomic sites. Thus, an
      instructive signal in sex determination can arise by duplication and
      neofunctionalization of an essential splicing regulator.

PMID- 28495754
TI  - PHD3 is a transcriptional coactivator of HIF-1alpha in nucleus pulposus cells
      independent of the PKM2-JMJD5 axis.
AB  - The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1alpha
      cofactor is controversial and remains unknown in skeletal tissues. We
      investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus
      pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain-
      containing protein (JMJD5) axis. PHD3-/- mice (12.5 mo old) showed increased
      incidence of intervertebral disc degeneration with a concomitant decrease in
      expression of the HIF-1alpha targets VEGF-A, glucose transporter-1, and lactate
      dehydrogenase A. PHD3 silencing decreased hypoxic activation of HIF-1alpha C
      terminal transactivation domain (C-TAD), but not HIF-1alpha-N-terminal-(N)-TAD or
      HIF-2alpha-TAD. Moreover, PHD3 suppression in NP cells resulted in decreased HIF
      1alpha enrichment on target promoters and lower expression of select HIF-1
      targets. Contrary to other cell types, manipulation of PKM2 and JMJD5 levels had
      no effect on HIF-1 activity in NP cells. Likewise, stabilization of tetrameric
      PKM2 by a chemical approach had no effect on PHD3-dependent HIF-1 activity.
      Coimmunoprecipitation assays showed lack of association between HIF-1alpha and
      PKM2 in NP cells. Results support the role of the PHD3 as a cofactor for HIF-1,
      independent of PKM2-JMJD5.-Schoepflin, Z. R., Silagi, E. S., Shapiro, I. M.,
      Risbud, M. V. PHD3 is a transcriptional coactivator of HIF-1alpha in nucleus
      pulposus cells independent of the PKM2-JMJD5 axis.

PMID- 28495755
TI  - Intestinal microbiota contributes to colonic epithelial changes in simulated
      microgravity mouse model.
AB  - Exposure to microgravity leads to alterations in multiple systems, but
      microgravity-related changes in the gastrointestinal tract and its clinical
      significance have not been well studied. We used the hindlimb unloading (HU)
      mouse model to simulate a microgravity condition and investigated the changes in
      intestinal microbiota and colonic epithelial cells. Compared with ground-based
      controls (Ctrls), HU affected fecal microbiota composition with a profile that
      was characterized by the expansion of Firmicutes and decrease of Bacteroidetes.
      The colon epithelium of HU mice showed decreased goblet cell numbers, reduced
      epithelial cell turnover, and decreased expression of genes that are involved in
      defense and inflammatory responses. As a result, increased susceptibility to
      dextran sulfate sodium-induced epithelial injury was observed in HU mice.
      Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in
      Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these
      epithelial changes in HU mice. Results indicate that HU changes intestinal
      microbiota, which leads to altered colonic epithelial cell homeostasis, impaired
      barrier function, and increased susceptibility to colitis. We further demonstrate
      that alteration in gastrointestinal motility may contribute to HU-associated
      dysbiosis. These animal results emphasize the necessity of evaluating astronauts'
      intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J.,
      Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H.,
      Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in
      simulated microgravity mouse model.

PMID- 28495756
TI  - Cystic fibrosis transmembrane conductance regulator mediates tenogenic
      differentiation of tendon-derived stem cells and tendon repair: accelerating
      tendon injury healing by intervening in its downstream signaling.
AB  - Tendons are a mechanosensitive tissue, which enables them to transmit to bone
      forces that are derived from muscle. Patients with tendon injuries, such as
      tendinopathy or tendon rupture, were often observed with matrix degeneration, and
      the healing of tendon injuries remains a challenge as a result of the limited
      understanding of tendon biology. Our study demonstrates that the stretch-mediated
      activation channel, cystic fibrosis transmembrane conductance regulator (CFTR),
      was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic
      differentiation under mechanical stretching. Tendon tissues in CFTR-dysfunctional
      DF508 mice exhibited irregular cell arrangement, uneven fibril diameter
      distribution, weak mechanical properties, and less matrix formation in a tendon
      defect model. Moreover, both tendon tissues and TDSCs isolated from DF508 mice
      showed significantly decreased levels of tendon markers, such as scleraxis,
      tenomodulin, Col1A1 (collagen type I alpha 1 chain), and decorin Furthermore, by
      RNA sequencing analysis, we demonstrated that Wnt/beta-catenin signaling was
      abnormally activated in TDSCs from DF508 mice, thereby further activating the
      pERK1/2 signaling pathway. Of most importance, we found that intervention in
      pERK1/2 signaling could promote tenogenic differentiation and tendon regeneration
      both in vitro and in vivo Taken together, our study demonstrates that CFTR plays
      an important role in tenogenic differentiation and tendon regeneration by
      inhibiting the beta-catinin/pERK1/2 signaling pathway. The therapeutic strategy
      of intervening in the CFTR/beta-catenin/pERK1/2 regulatory axis may be helpful
      for accelerating tendon injury healing, which has implications for tendon injury
      management.-Liu, Y., Xu, J., Xu, L., Wu, T., Sun, Y., Lee, Y.-W., Wang, B., Chan,
      H.-C., Jiang, X., Zhang, J., Li, G. Cystic fibrosis transmembrane conductance
      regulator mediates tenogenic differentiation of tendon-derived stem cells and
      tendon repair: accelerating tendon injury healing by intervening in its
      downstream signaling.

PMID- 28495757
TI  - Complete Genome Sequence of a Novel Multidrug-Resistant Klebsiella pneumoniae
      Phage, vB_Kpn_IME260.
AB  - Klebsiella pneumoniae is the most common clinically important opportunistic
      bacterial pathogen and its infection is often iatrogenic. Its drug resistance
      poses a grave threat to public health. The genomic data reported here comprise an
      important resource for research on phage therapy in the control of drug-resistant
      bacteria.

PMID- 28495758
TI  - Draft Genome Sequences of Enterohemorrhagic Escherichia coli O103:H2 Strains
      Isolated from Feces of Feedlot Cattle.
AB  - The enterohemorrhagic pathotype represents a minor proportion of the Escherichia
      coli O103 strains shed in the feces of cattle. We report here the genome
      sequences of 43 strains of enterohemorrhagic E. coli (EHEC) O103:H2 isolated from
      feedlot cattle feces. The genomic analysis will provide information on the
      genetic diversity and virulence potential of bovine EHEC O103.

PMID- 28495759
TI  - Complete Genome Sequences of Two Phage-Like Plasmids Carrying the CTX-M-15
      Extended-Spectrum beta-Lactamase Gene.
AB  - Two similar phage-like plasmids carrying CTX-M-15 resistance cassettes were
      identified from two environmental Escherichia coli isolates. They demonstrate
      strong nucleotide sequence identity to the phage-like plasmid pECOH89 and
      Salmonella bacteriophage SSU5.

PMID- 28495760
TI  - AnCo3, a New Member of the Emerging Family of Phage-Like Plasmids.
AB  - A phage-like plasmid isolated from a clinical isolate of Salmonella enterica
      serovar Derby has strong nucleotide sequence identity to the phage-like plasmids
      pSTM_phi isolated from Salmonella enterica serovar Typhimurium L495, AnCo1 and
      AnCo2 from Escherichia coli 243 and Escherichia coli 244, and the virulent
      Salmonella-specific SSU5 bacteriophage.

PMID- 28495761
TI  - Genome Sequence of a Bovine Rhinitis B Virus Identified in Cattle in Sweden.
AB  - A bovine rhinitis B virus, identified in a calf from Sweden, was genetically
      characterized. The complete polyprotein was recovered, and phylogenetic analysis
      showed that this virus has the highest similarity to a bovine rhinitis B virus
      previously identified in Mexico.

PMID- 28495763
TI  - Draft Genome Sequences of Serratia marcescens Strains CAPREx SY13 and CAPREx SY21
      Isolated from Yams.
AB  - Serratia marcescens strains CAPREx SY13 and CAPREx SY21 were isolated from
      Ghanaian yams from a London market. The draft genomes suggest that the strains
      are similar, with genomes of 5,308,004 and 5,157,134 bp and 59.35 and 59.62 G+C%,
      respectively. The genes necessary for prodigiosin biosynthesis were present in
      both strains.

PMID- 28495762
TI  - Draft Genome Sequences of 25 Listeria monocytogenes Isolates Associated with
      Human Clinical Listeriosis in Ireland.
AB  - Listeria monocytogenes is a Gram-positive opportunistic pathogen that is the
      causative agent of listeriosis. Here, we report the draft genome sequences of 25
      L. monocytogenes strains isolated from patients with clinical listeriosis in the
      Republic of Ireland between 2013 and 2015.

PMID- 28495764
TI  - Draft Genome Sequence of Geobacillus sp. LEMMY01, a Thermophilic Bacterium
      Isolated from the Site of a Burning Grass Pile.
AB  - We report here the 3,586,065-bp draft genome of Geobacillus sp. LEMMY01, which
      was isolated (axenic culture) from a thermophilic chemolitoautotrophic consortium
      obtained from the site of a burning grass pile. The genome contains biosynthetic
      gene clusters coding for secondary metabolites, such as terpene and lantipeptide,
      confirming the biotechnological potential of this strain.

PMID- 28495765
TI  - Complete Genome Sequence of Bacteriophage SEN8, a Temperate Phage Isolated from
      Salmonella enterica subsp. salamae.
AB  - A temperate phage, SEN8, having a broad activity against pathogenic Salmonella
      serovars, was isolated from Salmonella enterica subsp. salamae strain Sen8. The
      complete genome sequence of phage SEN8 was determined (35,203 bp) and showed
      relatedness to P2-like phages (Salmonella phages Fels-2 and RE-2010).

PMID- 28495766
TI  - Ten Genome Sequences of Human and Livestock Isolates of Bacillus anthracis from
      the Country of Georgia.
AB  - Bacillus anthracis causes the acute fatal disease anthrax, is a proven biological
      weapon, and is endemic in Georgia, where human and animal cases are reported
      annually. Here, we present whole-genome sequences of 10 historical B. anthracis
      strains from Georgia.

PMID- 28495767
TI  - Complete Genome Sequences of 12 Isolates of Listeria monocytogenes Belonging to
      Serotypes 1/2a, 1/2b, and 4b Obtained from Food Products and Food-Processing
      Environments in Canada.
AB  - Listeria monocytogenes is the etiological agent for an often fatal foodborne
      illness known as listeriosis. Here, we present the complete genome sequences of
      12 L. monocytogenes isolates representing the three most common serotypes of this
      pathogen (1/2a, 1/2b, and 4b), collected in Canada from different food products
      and environmental sources.

PMID- 28495768
TI  - Complete Genome Sequence of an Enterovirus 71 Strain Isolated from the
      Cerebrospinal Fluid of a Child with Severe Hand-Foot-and-Mouth Disease in Yunnan,
      China, 2013.
AB  - The complete genome sequence of the enterovirus 71 strain CSF15/YN/CHN/2013,
      first isolated from cerebrospinal fluid of a child in Yunnan, China, in 2013, was
      determined. According to the phylogenetic and homogeneity analyses, the isolate
      was assigned to subgenotype C4a.

PMID- 28495769
TI  - Draft Genome Sequence of Bacillus toyonensis VU-DES13, Isolated from Folsomia
      candida (Collembola: Entomobryidae).
AB  - We present here the draft genome of Bacillus toyonensis VU-DES13, which was
      isolated from the midgut of the soil-living springtail Folsomia candida Previous
      research revealed the presence of gene clusters for the biosynthesis of various
      secondary metabolites, including beta-lactam antibiotics, in the host's genome.
      The genome data are discussed in the light of the antimicrobial properties
      against fungi and oomycetes and a high level of beta-lactam resistance of the
      isolate.

PMID- 28495770
TI  - Complete Genome Sequence of the Bacterium Bacillus circulans Jordan Strain 32352.
AB  - Here, we report the complete genome sequence for the Bacillus circulans Jordan
      strain 32352. This species is a soil dwelling bacterium that expresses glycosyl
      hydrolase enzymes degrading pneumococcal capsular polysaccharides.

PMID- 28495771
TI  - Complete Genome Sequence of the Disinfectant Susceptibility Testing Reference
      Strain Staphylococcus aureus subsp. aureus ATCC 6538.
AB  - We report here the complete genome sequence of the methicillin-sensitive
      Staphylococcus aureus subsp. aureus strain ATCC 6538 (FDA 209, DSM 799, WDCM
      00032, and NCTC 10788).

PMID- 28495772
TI  - Complete Genome Sequence of the Livestock-Associated Methicillin-Resistant Strain
      Staphylococcus aureus subsp. aureus 08S00974 (Sequence Type 398).
AB  - We report here the complete genome sequence of the livestock-associated
      methicillin-resistant Staphylococcus aureus strain 08S00974 from sequence type
      398 (ST398 LA-MRSA) isolated from a fatting pig at a farm in Germany.

PMID- 28495773
TI  - New Sequence Types of Vibrio parahaemolyticus Isolated from a Malaysian
      Aquaculture Pond, as Revealed by Whole-Genome Sequencing.
AB  - The acquisition of Photorhabdus insect-related (Pir) toxin-like genes in Vibrio
      parahaemolyticus has been linked to hepatopancreatic necrosis disease in shrimp.
      We report the whole-genome sequences of genetically virulent and avirulent V.
      parahaemolyticus isolated from a Malaysian aquaculture pond and show that they
      represent previously unreported sequence types of V. parahaemolyticus.

PMID- 28495774
TI  - Whole-Genome Sequence of Endophytic Plant Growth-Promoting Escherichia coli
      USML2.
AB  - Escherichia coli strain USML2 was originally isolated from the inner leaf tissues
      of surface-sterilized phytopathogenic-free oil palm (Elaeis guineensis Jacq.). We
      present here the whole-genome sequence of this plant-endophytic strain. The
      genome consists of a single circular chromosome of 4,502,758 bp, 4,315 predicted
      coding sequences, and a G+C content of 50.8%.

PMID- 28495775
TI  - Complete Coding Sequence of a Case of Chikungunya Virus Imported into Australia.
AB  - A case of chikungunya virus infection was imported from India into Australia in
      late 2016. Infection was diagnosed by real-time reverse transcription-PCR and
      confirmed by culture isolation and genome sequencing. Phylogenetic analysis of
      the genome sequence indicated that the virus grouped with the east/central/south
      African genotype.

PMID- 28495776
TI  - Analysis of an RNA-seq Strand-Specific Library from an East Timorese Cucumber
      Sample Reveals a Complete Cucurbit aphid-borne yellows virus Genome.
AB  - Analysis of an RNA-seq library from cucumber leaf RNA extracted from a fast
      technology for analysis of nucleic acids (FTA) card revealed the first complete
      genome of Cucurbit aphid-borne yellows virus (CABYV) from East Timor. We compare
      it with 35 complete CABYV genomes from other world regions. It most resembled the
      genome of the South Korean isolate HD118.

PMID- 28495777
TI  - Complete Annotated Genome Sequences of Two Shiga Toxin-Producing Escherichia coli
      Strains and One Atypical Enteropathogenic E. coli Strain, Isolated from Naturally
      Colonized Cattle of German Origin.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains are important zoonotic
      enteric pathogens with the main reservoir in cattle. Here, we present the genomes
      of two STEC strains and one atypical enteropathogenic E. coli strain from cattle
      origin, obtained during a longitudinal study in German cattle herds.

PMID- 28495778
TI  - Draft Genome of the Heterotrophic Iron-Oxidizing Bacterium "Acidibacillus
      ferroxidans" Huett2, Isolated from a Mine Drainage Ditch in Freiberg, Germany.
AB  - Here, we communicate the draft genome of "Acidibacillus ferrooxidans" Huett2, a
      novel strain of an acidophilic, heterotrophic, iron-oxidizing bacterium belonging
      to the phylum Firmicutes It was isolated from a water drainage system of a former
      minefield in Freiberg, Germany.

PMID- 28495779
TI  - Complete Genome Sequence of Mycoplasma bovis Strain 08M.
AB  - Mycoplasma bovis is a major bacterial pathogen that can cause respiratory
      disease, mastitis, and arthritis in cattle. We report here the complete and
      annotated genome sequence of M. bovis strain 08M, isolated from a calf lung with
      pneumonia in China.

PMID- 28495780
TI  - Genome Sequences of Listeria monocytogenes Strains with Resistance to Arsenic.
AB  - Listeria monocytogenes frequently exhibits resistance to arsenic. We report here
      the draft genome sequences of eight genetically diverse arsenic-resistant L.
      monocytogenes strains from human listeriosis and food-associated environments.
      The availability of these genomes will help elucidate the role of heavy-metal
      resistance in the ecology of L. monocytogenes.

PMID- 28495781
TI  - Draft Genome Sequence of Lawsonia intracellularis Strain E40504, Isolated from a
      Horse Diagnosed with Equine Proliferative Enteropathy.
AB  - Reported herein is the draft genome sequence of equine-origin Lawsonia
      intracellularis strain E40504, an obligate intracellular bacterium and the
      etiological agent of equine proliferative enteropathy. The 1.69-Mb draft genome
      sequence includes 1,380 protein-coding genes and 49 RNA genes, and it lacks a
      genomic island reported in swine-origin L. intracellularis strain PHE/MN1-00.

PMID- 28495782
TI  - Draft Genome Sequence of Staphylococcus fleurettii Strain MBTS-1 Isolated from
      Cucumber.
AB  - The draft genome of Staphylococcus fleurettii MBTS-1, isolated from cucumber in
      northern Germany, was sequenced. Analysis showed that the assembled genome had a
      size of 2,582,128 bp with a predicted total of 2,491 protein-encoding genes, 9
      rRNAs, 5 ncRNAs, and 44 tRNAs. This strain did not contain plasmid DNA.

PMID- 28495783
TI  - Draft Genome Sequence of Streptococcus dysgalactiae subsp. equisimilis Strain
      C161L1 Isolated in Vellore, India.
AB  - Streptococcus dysgalactiae subsp. equisimilis belongs to the beta-hemolytic group
      C and G pyogenic group of streptococci. Here, we report the draft genome of the
      S. dysgalactiae subsp. equisimilis strain C161L1 from Vellore, a region in
      southern India with a high incidence rate of S. dysgalactiae subsp. equisimilis
      infection. This genome is 2.1 Mb long, with a 39.82% G+C content, and encodes
      2,022 genes.

PMID- 28495784
TI  - Implication of Sialidases in Salmonella Infection: Genome Release of Sialidase
      Knockout Strains from Salmonella enterica Serovar Typhimurium LT2.
AB  - Sialidases, which are widely distributed in nature, cleave the alpha-ketosidic
      bond of terminal sialic acid residue. These emerging virulence factors degrade
      the host glycan. We report here the release of seven sialidase and one sialic
      acid transporter deletion in Salmonella enterica serovar Typhimurium strain LT2,
      which are important in cellular invasion during infection.

PMID- 28495785
TI  - Draft Genome Sequence of Plant Growth-Promoting Endophytic Streptomyces sp. GKU
      895 Isolated from the Roots of Sugarcane.
AB  - Streptomyces sp. GKU 895 is an endophytic actinomycete isolated from the roots of
      sugarcane. GKU 895 has a genome of 8.3 Mbp and the genome exhibits adaptations
      related to plant growth-promoting activity. It also has extensive specialized
      metabolite biosynthetic gene clusters apparent in its genome.

PMID- 28495786
TI  - Speaking fluently with baclofen?
AB  - Baclofen is a new and promising pharmacological compound for the treatment of
      alcohol dependence (AD). Although several randomised trials found a reduction of
      craving and higher abstinence rates with low and high doses of baclofen, others
      failed to show positive effects. In this case study, the successful treatment of
      a patient with AD with daily 120 mg of baclofen is described. In addition to a
      decrease in alcohol use, we observed the cessation of stuttering during treatment
      with baclofen, reoccurrence of stuttering following discontinuation, and
      cessation of stuttering after reinstatement of the treatment. Based on this
      observation, the direct effects of baclofen on muscle relaxation and anxiety
      reduction and its indirect effect on dopaminergic inhibition, we believe that
      baclofen might be a new treatment for stuttering. Further research into the
      effect of baclofen on stuttering is warranted.

PMID- 28495787
TI  - Screening contacts of patients with extrapulmonary TB for latent TB infection.
AB  - 2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply
      that contacts of extrapulmonary TB do not require screening for latent TB
      infection. At our high TB prevalence site, we identified 189 active cases of TB
      for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and
      10.7% of the contacts of extrapulmonary TB had active or latent TB infection.
      This supports screening contacts of extrapulmonary TB at our site and presents a
      way to access high-risk individuals. We propose to continue to screen the
      contacts of our patients with extrapulmonary TB and recommend other TB units
      audit their local results.

PMID- 28495788
TI  - Contraception advice for women with epilepsy.

PMID- 28495789
TI  - Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress
      allergic inflammation in intestine via targeting dendritic cell maturation.
AB  - Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long
      chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V (Bb)
      (GF/Bb) suppresses food allergic symptoms in mice, potentially via intestinal
      epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed
      galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory
      capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In
      this study, we investigated whether GF/Bb modulates dendritic cells (DCs) and
      subsequent Th2 and regulatory T cell (Treg) frequency in the small intestinal
      lamina propria (SI-LP). BALB/c mice were fed GF/Bb during oral OVA sensitization.
      DC and T cell phenotype were determined in SI-LP mononuclear cells using flow
      cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant
      galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC
      conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/Bb reduced
      allergic symptoms and enhanced serum galectin-9 levels, while suppressing
      activation, restoring phagocytic capacity, and normalizing CD103 expression of SI
      LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced
      activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium
      suppressed moDC activation in a galectin-9-dependent manner. Besides suppression
      of SI-LP DC activation, dietary GF/Bb also lowered the frequency of activated Th2
      cells, while enhancing Treg in the SI-LP of OVA-allergic mice compared to the
      control diet. Dietary intervention with GF/Bb enhances galectin-9 and suppresses
      allergic symptoms of OVA-allergic mice in association with reduced intestinal DC
      and Th2 activation and increased Treg frequency in these mice.

PMID- 28495790
TI  - Systemic inflammatory response syndrome-related lymphopenia is associated with
      adenosine A1 receptor dysfunction.
AB  - SIRS is associated with lymphopenia, and prolonged lymphopenia of septic patients
      has been associated with increased mortality risk. We hypothesize that elevated
      adenosine during SIRS down-regulates Gi-coupled A1R, which signals an effect that
      sensitizes a cAMP-dependent lymphotoxic response. In this study, we evaluate the
      role of adenosine in SIRS-mediated lymphopenia and impaired IL-15 production.
      Cecal ligation and puncture was used to induce sepsis-associated SIRS in mice.
      BMDCs were cultured and used to measure the effect of adenosine on IL-15. We
      found that A1R mRNA levels were significantly down-regulated and A1R-dependent Gi
      activity was abolished in T cells of septic mice. In accordance, cAMP was
      elevated in isolated T cells from cecal ligation and puncture compared with sham
      treated mice. Similar to septic mice, leukopenia was evident in sham A1R-KO mice,
      after treatment with the A1R antagonist (8-cyclopentyl-1,3-dipropylxanthine), or
      after A1R desensitization. In contrast, A2AR-KO mice were protected from
      leukopenia. In addition, we observed that septic A1R-KO mice exhibited low IL-15
      levels. Cultured BMDC agonists of A2AR and A2BR inhibited IL-15 production and
      adenosine blocked IL-15-dependent proliferation of cytotoxic T cells that were
      cocultured with stimulated BMDCs. To conclude, we suggest that SIRS-associated
      lymphopenia is initiated by A1R desensitization and adenosine-mediated inhibition
      of IL-15 production is part of the mechanism that accounts for the delay in
      leukopenia recovery in patients with severe sepsis. Interference with adenosine
      signaling may thus be potentially beneficial for septic patients with leukopenia.

PMID- 28495791
TI  - Death rate now rising in UK's poorest infants.

PMID- 28495792
TI  - CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27
      expressing B-cell malignancies.
AB  - The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand
      CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory
      signals to cytotoxic T cells but also increases the frequency of regulatory T
      cells. Similar to other TNFR ligands, CD70 has been shown to initiate
      intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a
      majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of
      lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion
      mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the
      immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on
      malignant cells increased the number of tumor-infiltrating interferon gamma
      producing natural killer (NK) cells. In contrast, the antitumoral T-cell response
      remained largely unchanged. CD70 reverse signaling in NK cells was mediated via
      the AKT signaling pathway and increased NK cell survival and effector function.
      The improved immune control by activated NK cells prolonged survival of CD27
      trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced
      survival and effector function of human NK cells in a B-cell acute lymphoblastic
      leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells
      contributes to the immune control of CD27-expressing B-cell lymphoma and
      leukemia.

PMID- 28495793
TI  - USP7 inhibition alters homologous recombination repair and targets CLL cells
      independently of ATM/p53 functional status.
AB  - The role of deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation
      of the p53-dependent DNA damage response (DDR) pathway is well established.
      Whereas previous studies have mostly focused on the mechanisms underlying how
      USP7 directly controls p53 stability, we recently showed that USP7 modulates the
      stability of the DNA damage responsive E3 ubiquitin ligase RAD18. This suggests
      that targeting USP7 may have therapeutic potential even in tumors with defective
      p53 or ibrutinib resistance. To test this hypothesis, we studied the effect of
      USP7 inhibition in chronic lymphocytic leukemia (CLL) where the ataxia
      telangiectasia mutated (ATM)-p53 pathway is inactivated with relatively high
      frequency, leading to treatment resistance and poor clinical outcome. We
      demonstrate that USP7 is upregulated in CLL cells, and its loss or inhibition
      disrupts homologous recombination repair (HRR). Consequently, USP7 inhibition
      induces significant tumor-cell killing independently of ATM and p53 through the
      accumulation of genotoxic levels of DNA damage. Moreover, USP7 inhibition
      sensitized p53-defective, chemotherapy-resistant CLL cells to clinically
      achievable doses of HRR-inducing chemotherapeutic agents in vitro and in vivo in
      a murine xenograft model. Together, these results identify USP7 as a promising
      therapeutic target for the treatment of hematological malignancies with DDR
      defects, where ATM/p53-dependent apoptosis is compromised.

PMID- 28495794
TI  - An endpoint associated with clinical benefit after initial treatment of chronic
      graft-versus-host disease.
AB  - No gold standard has been established as a primary endpoint in trials of initial
      treatment of chronic graft-versus-host disease (GVHD), and evidence showing the
      association of any proposed primary endpoint with clinical benefit has not been
      conclusively demonstrated. To address this gap, we analyzed outcomes in a cohort
      of 328 patients enrolled in a prospective, multicenter, observational study
      within 3 months after diagnosis of chronic GVHD. Complete and partial response,
      stable disease, and progressive disease were defined according to the 2014
      National Institutes of Health Consensus Development Conference on Criteria for
      Clinical Trials in Chronic Graft-Versus-Host Disease. Success was defined as
      complete or partial response with no secondary systemic treatment or recurrent
      malignancy at 1 year after enrollment. Success was observed in fewer than 20% of
      the patients. The burden of disease manifestations at 1 year was lower for
      patients in this category than for those with stable or progressive disease.
      Systemic treatment ended earlier, and subsequent mortality was lower among
      patients with complete or partial response than among those with stable or
      progressive disease and those who had received secondary systemic treatment. We
      conclude that survival with a complete or partial response and no previous
      secondary systemic treatment or recurrent malignancy at 1 year after initial
      systemic therapy is associated with clinical benefit, a critical characteristic
      for consideration as a primary endpoint in a pivotal clinical trial. This
      prospective observational study was registered at www.clinicaltrials.gov as
      #NCT00637689.

PMID- 28495795
TI  - The desmoplakin-intermediate filament linkage regulates cell mechanics.
AB  - The translation of mechanical forces into biochemical signals plays a central
      role in guiding normal physiological processes during tissue development and
      homeostasis. Interfering with this process contributes to cardiovascular disease,
      cancer progression, and inherited disorders. The actin-based cytoskeleton and its
      associated adherens junctions are well-established contributors to mechanosensing
      and transduction machinery; however, the role of the desmosome-intermediate
      filament (DSM-IF) network is poorly understood in this context. Because a force
      balance among different cytoskeletal systems is important to maintain normal
      tissue function, knowing the relative contributions of these structurally
      integrated systems to cell mechanics is critical. Here we modulated the
      interaction between DSMs and IFs using mutant forms of desmoplakin, the protein
      bridging these structures. Using micropillar arrays and atomic force microscopy,
      we demonstrate that strengthening the DSM-IF interaction increases cell-substrate
      and cell-cell forces and cell stiffness both in cell pairs and sheets of cells.
      In contrast, disrupting the interaction leads to a decrease in these forces.
      These alterations in cell mechanics are abrogated when the actin cytoskeleton is
      dismantled. These data suggest that the tissue-specific variability in DSM-IF
      network composition provides an opportunity to differentially regulate tissue
      mechanics by balancing and tuning forces among cytoskeletal systems.

PMID- 28495796
TI  - Phosphorylation of NHE3-S719 regulates NHE3 activity through the formation of
      multiple signaling complexes.
AB  - Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively
      phosphorylates a downstream site (S719) that accounts for 40% of basal NHE3
      activity. The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe
      cells was further examined by mutation of NHE3-S719 to A (not phosphorylated) or
      D (phosphomimetic). NHE3-S719A but not -S719D had multiple changes in NHE3
      activity: 1) reduced basal NHE3 activity-specifically, inhibition of the PI3K/AKT
      dependent component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R
      stimulation; and 3) reduced acute inhibition of NHE3 activity-specifically,
      elevated Ca2+ related (carbachol/Ca2+ ionophore), but there was normal inhibition
      by forskolin and hyperosmolarity. The S719A mutant had reduced NHE3 complex size,
      reduced expression in lipid rafts, increased BB mobile fraction, and reduced
      binding to multiple proteins that bind throughout the NHE3 intracellular C
      terminus, including calcineurin homologous protein, the NHERF family and SNX27
      (related PDZ domains). These studies show that phosphorylation of the NHE3 at a
      single amino acid in the distal part of the C-terminus affects multiple aspects
      of NHE3 complex formation and changes the NHE3 lipid raft distribution, which
      cause changes in specific aspects of basal as well as acutely stimulated and
      inhibited Na+/H+ exchange activity.

PMID- 28495798
TI  - A role for Sar1 and ARF1 GTPases during Golgi biogenesis in the protozoan
      parasite Trypanosoma brucei.
AB  - A single Golgi stack is duplicated and partitioned into two daughter cells during
      the cell cycle of the protozoan parasite Trypanosoma brucei The source of
      components required to generate the new Golgi and the mechanism by which it forms
      are poorly understood. Using photoactivatable GFP, we show that the existing
      Golgi supplies components directly to the newly forming Golgi in both intact and
      semipermeabilized cells. The movement of a putative glycosyltransferase, GntB,
      requires the Sar1 and ARF1 GTPases in intact cells. In addition, we show that
      transfer of GntB from the existing Golgi to the new Golgi can be recapitulated in
      semipermeabilized cells and is sensitive to the GTP analogue GTPgammaS. We
      suggest that the existing Golgi is a key source of components required to form
      the new Golgi and that this process is regulated by small GTPases.

PMID- 28495797
TI  - Ixazomib enhances parathyroid hormone-induced beta-catenin/T-cell factor
      signaling by dissociating beta-catenin from the parathyroid hormone receptor.
AB  - The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt
      independent activation of beta-catenin/T-cell factor (TCF) signaling. beta
      Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC
      activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the
      first orally administered proteasome inhibitor for the treatment of multiple
      myeloma; it acts in part by inhibition of pathological bone destruction.
      Proteasome inhibitors were reported to stabilize beta-catenin by the ubiquitin
      proteasome pathway. However, how Izb affects PTHR activation to regulate beta
      catenin/TCF signaling is poorly understood. In the present study, using
      CRISPR/Cas9 genome-editing technology, we show that Izb reverses beta-catenin
      mediated PTHR signaling switch and enhances PTH-induced cAMP generation and cAMP
      response element-luciferase activity in osteoblasts. Izb increases active forms
      of beta-catenin and promotes beta-catenin translocation, thereby dissociating
      beta-catenin from the PTHR at the plasma membrane. Furthermore, Izb facilitates
      PTH-stimulated GSK3beta phosphorylation and beta-catenin phosphorylation. Thus
      Izb enhances PTH stimulation of beta-catenin/TCF signaling via cAMP-dependent
      activation, and this effect is due to its separating beta-catenin from the PTHR.
      These findings provide evidence that Izb may be used to improve the therapeutic
      efficacy of PTH for the treatment of osteoporosis and other resorptive bone
      diseases.

PMID- 28495799
TI  - Truncating mutations of SPAST associated with hereditary spastic paraplegia
      indicate greater accumulation and toxicity of the M1 isoform of spastin.
AB  - The SPAST gene, which produces two isoforms (M1 and M87) of the microtubule
      severing protein spastin, is the chief gene mutated in hereditary spastic
      paraplegia. Haploinsufficiency is a popular explanation for the disease, in part
      because most of the >200 pathogenic mutations of the gene are truncating and
      expected to produce only vanishingly small amounts of shortened proteins. Here we
      studied two such mutations, N184X and S245X, and our results suggest another
      possibility. We found that the truncated M1 proteins can accumulate to notably
      higher levels than their truncated M87 or wild-type counterparts. Reminiscent of
      our earlier studies on a pathogenic mutation that generates full-length M1 and
      M87 proteins, truncated M1 was notably more detrimental to neurite outgrowth than
      truncated M87, and this was true for both N184X and S245X. The greater toxicity
      and tendency to accumulate suggest that, over time, truncated M1 could damage the
      corticospinal tracts of human patients. Curiously, the N184X mutation triggers
      the reinitiation of translation at a third start codon in SPAST, resulting in
      synthesis of a novel M187 spastin isoform that is able to sever microtubules.
      Thus microtubule severing may not be as reduced as previously assumed in the case
      of that mutation.

PMID- 28495800
TI  - Mechanically patterned neuromuscular junctions-in-a-dish have improved functional
      maturation.
AB  - Motor neuron (MN) diseases are progressive disorders resulting from degeneration
      of neuromuscular junctions (NMJs), which form the connection between MNs and
      muscle fibers. NMJ-in-a-dish models have been developed to examine human MN
      associated dysfunction with disease; however such coculture models have randomly
      oriented myotubes with immature synapses that contract asynchronously.
      Mechanically patterned (MP) extracellular matrix with alternating soft and stiff
      stripes improves current NMJ-in-a-dish models by inducing both mouse and human
      myoblast durotaxis to stripes where they aligned, differentiated, and fused into
      patterned myotubes. Compared to conventional culture on rigid substrates or
      unpatterned hydrogels, MP substrates supported increased differentiation and
      fusion, significantly larger acetylcholine (ACh) receptor clusters, and increased
      expression of MuSK and Lrp4, two cell surface receptors required for NMJ
      formation. Robust contractions were observed when mouse myotubes were stimulated
      by ACh, with twitch duration and frequency most closely resembling those for
      mature muscle on MP substrates. Fused myotubes, when cocultured with MNs, were
      able to form even larger NMJs. Thus MP matrices produce more functionally active
      NMJs-in-a-dish, which could be used to elucidate disease pathology and facilitate
      drug discovery.

PMID- 28495802
TI  - A common NHE3 single-nucleotide polymorphism has normal function and sensitivity
      to regulatory ligands.
AB  - Na+/H+ exchanger NHE3 mediates the majority of intestinal and renal
      electroneutral sodium absorption. Dysfunction of NHE3 is associated with a
      variety of diarrheal diseases. We previously reported that the NHE3 gene (SLC9A3)
      has more than 400 single-nucleotide polymorphisms (SNPs) but few nonsynonymous
      polymorphisms. Among the latter, one polymorphism (rs2247114-G>A), which causes a
      substitution from arginine to cysteine at amino acid position 799 (p.R799C), is
      common in Asian populations. To improve our understanding of the population
      distribution and potential clinical significance of the NHE3-799C variant, we
      investigated the frequency of this polymorphism in different ethnic groups using
      bioinformatics analyses and in a cohort of Japanese patients with cardiovascular
      or renal disease. We also characterized the function of human NHE3-799C and its
      sensitivity to regulatory ligands in an in vitro model. NHE3-799C had an allele
      frequency of 29.5-57.6% in Asian populations, 11.1-23.6% in European populations,
      and 10.2-22.7% in African populations. PS120/FLAG-NHERF2 fibroblasts stably
      expressing NHE3-799C had lower total protein expression but a higher percentage
      of surface expression than those expressing NHE3-799R. NHE3-799C had similar
      basal activity to NHE3-799R and was similarly stimulated or inhibited, by serum
      or forskolin, respectively. Tenapanor, a small-molecule NHE3 inhibitor, dose
      dependently inhibited NHE3-799R and NHE3-799C activities. The IC50 values of
      tenapanor for NHE3-799C and NHE3-799R were significantly different, but both were
      in the nanomolar range. These results suggest that NHE3-799C is a common variant
      enriched in Asian populations, is not associated with compromised function or
      abnormal regulation, and is unlikely to contribute to clinical disease.NEW &
      NOTEWORTHY This study reports results on the functional significance of human
      NHE3-799C under basal conditions and in response to regulatory ligands, including
      a novel NHE3 inhibitor called tenapanor. We demonstrate that NHE3-799C is a
      common variant of NHE3 that is enriched in Asian populations; however, in
      contrast to our previous studies using rabbit NHE3, its presence seems to have
      limited clinical significance in humans and is not associated with compromised
      function or abnormal transport regulation.

PMID- 28495805
TI  - Hans Tol #PromiseAndDeliver #ToughBrainyStraightforward.

PMID- 28495804
TI  - Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of
      the shoulder: a three-armed randomised clinical trial.
AB  - BACKGROUND: Labral repair and biceps tenodesis are routine operations for
      superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of
      their efficacy is lacking. We evaluated the effect of labral repair, biceps
      tenodesis and sham surgery on SLAP lesions. METHODS: A double-blind, sham
      controlled trial was conducted with 118 surgical candidates (mean age 40 years),
      with patient history, clinical symptoms and MRI arthrography indicating an
      isolated type II SLAP lesion. Patients were randomly assigned to either labral
      repair (n=40), biceps tenodesis (n=39) or sham surgery (n=39) if arthroscopy
      revealed an isolated SLAP II lesion. Primary outcomes at 6 and 24 months were
      clinical Rowe score ranging from 0 to 100 (best possible) and Western Ontario
      Shoulder Instability Index (WOSI) ranging from 0 (best possible) to 2100.
      Secondary outcomes were Oxford Instability Shoulder Score, change in main
      symptoms, EuroQol (EQ-5D and EQ-VAS), patient satisfaction and complications.
      RESULTS: There were no significant between-group differences at any follow-up in
      any outcome. Between-group differences in Rowe scores at 2 years were: biceps
      tenodesis versus labral repair: 1.0 (95% CI -5.4 to 7.4), p=0.76; biceps
      tenodesis versus sham surgery: 1.6 (95% CI -5.0 to 8.1), p=0.64; and labral
      repair versus sham surgery: 0.6 (95% CI -5.9 to 7.0), p=0.86. Similar results-no
      differences between groups-were found for WOSI scores. Postoperative stiffness
      occurred in five patients after labral repair and in four patients after
      tenodesis. CONCLUSION: Neither labral repair nor biceps tenodesis had any
      significant clinical benefit over sham surgery for patients with SLAP II lesions
      in the population studied. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
      identifier: NCT00586742.

PMID- 28495806
TI  - Infographic: Athlete monitoring in sport-top tips.

PMID- 28495807
TI  - Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or
      Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.
AB  - BACKGROUND: Despite unprecedented efficacy across multiple tumor types, immune
      checkpoint inhibitor therapy is associated with a unique and wide spectrum of
      immune-related adverse events (irAEs), including neurologic events ranging from
      mild headache to potentially life-threatening encephalitis. Here, we summarize
      neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment,
      present cases of treatment-related encephalitis, and provide practical guidance
      on diagnosis and management. METHODS: We searched a Global Pharmacovigilance and
      Epidemiology database for neurologic irAEs reported over an 8-year period in
      patients with advanced melanoma receiving nivolumab with or without ipilimumab
      from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were
      reviewed, and relationship to nivolumab or ipilimumab was assigned. RESULTS: In
      our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious
      neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5),
      encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse
      events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or
      unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall,
      median time to onset was 45 days (range 1-170) and to resolution was 32 days (2
      809+). Median time to onset of encephalitis was 55.5 days (range 18-297); four
      cases resolved and one was fatal. CONCLUSION: Both oncologists and neurologists
      need to be aware of signs and symptoms of serious but uncommon neurologic irAEs
      associated with checkpoint inhibitors. Prompt diagnosis and management using an
      established algorithm are critical to minimize serious complications from these
      neurologic irAEs. IMPLICATIONS FOR PRACTICE: With increasing use of checkpoint
      inhibitors in cancer, practicing oncologists need to be aware of the potential
      risk of neurologic immune-related adverse events and be able to provide prompt
      treatment of this uncommon, but potentially serious, class of adverse events. We
      summarize neurologic adverse events related to nivolumab alone or in combination
      with ipilimumab in patients with advanced melanoma from 12 studies and examine in
      depth 6 cases of encephalitis. We also provide input and guidance on the existing
      neurologic adverse events management algorithm for nivolumab and ipilimumab.

PMID- 28495808
TI  - Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional
      Treatment Options.
AB  - BACKGROUND: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma,
      is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection
      combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with
      rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is
      of limited clinical benefit. MATERIALS AND METHODS: We queried whether
      comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover
      genomic alterations (GA) that could identify potential targeted therapies for
      these patients. CGP was performed on formalin-fixed, paraffin-embedded sections
      from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor
      ligation based next-generation sequencing assay to a mean coverage depth of 593X.
      The results were analyzed for base substitutions, insertions and deletions,
      select rearrangements, and copy number changes (amplifications and homozygous
      deletions). RESULTS: Clinically relevant GA (CRGA) were defined as GA linked to
      drugs on the market or under evaluation in clinical trials. A total of 28 ENBs
      harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs
      (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The
      most commonly altered gene was TP53 (17%), with GA in PIK3CA, NF1, CDKN2A, and
      CDKN2C occurring in 7% of samples. CONCLUSION: We report comprehensive genomic
      profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets,
      including targetable GA in the mTOR, CDK and growth factor signaling pathways,
      highlighting the clinical value of genomic profiling in ENB. IMPLICATIONS FOR
      PRACTICE: Comprehensive genomic profiling of 41 relapsed or refractory ENBs
      reveals recurrent alterations or classes of mutation, including amplification of
      tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the
      mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one
      clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per
      sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA,
      NF1, CDKN2A, or CDKN2C were identified in 7% of samples. Responses to treatment
      with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in
      conjunction with tumor genomics.

PMID- 28495810
TI  - Management of lipid-lowering therapy in patients with cardiovascular events in
      the UK: a retrospective cohort study.
AB  - OBJECTIVES: To describe low-density lipoprotein (LDL) cholesterol management and
      lipid-lowering treatment patterns in patients with a cardiovascular (CV) event.
      DESIGN: Retrospective cohort study using Clinical Practice Research Datalink
      records linked with Hospital Episode Statistics data. SETTING: Routine clinical
      practice in the UK from 2006 to 2012. PARTICIPANTS: Individuals >=18 years were
      selected at their first CV-related hospitalisation (first event cohort) if they
      had received >=2 lipid-lowering therapy prescriptions within 180 days beforehand.
      Patients were stratified into four mutually exclusive subgroups based on the
      presence or absence of vascular disease and of diabetes. Those with a second CV
      hospitalisation within 36 months were included in a separate cohort (second event
      cohort). PRIMARY AND SECONDARY OUTCOME MEASURES: LDL levels in the year prior to
      the CV event and 12 months later as well as measures of adherence to lipid
      lowering therapy during the 12 months after the CV hospitalisation. RESULTS:
      There were 24 093 patients in the first event cohort, of whom 5274 were included
      in the second event cohort. Most received moderate intensity statins at baseline
      and 12 months. Among the four first event cohort subgroups at baseline, the
      proportions with an LDL of <1.8 mmol/L was similar between the two diabetic
      cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts
      (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an
      LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The
      proportion of adherent patients (medication possession ratio of>=0.8) was highest
      for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%,
      and for fibrates, it was 48% to 62%. CONCLUSIONS: Despite the existence of
      effective therapies for lowering cholesterol, patients do not reach achievable
      LDL targets.

PMID- 28495809
TI  - Comparison of enteral versus intravenous potassium supplementation in
      hypokalaemia in paediatric patients in intensive care post cardiac surgery: open
      label randomised equivalence trial (EIPS).
AB  - OBJECTIVES: The primary objective was to compare the efficacy of enteral
      potassium replacement (EPR) and intravenous potassium replacement (IVPR) as first
      line therapy. Secondary objectives included comparison of adverse effects and
      number of doses required to resolve the episode of hypokalaemia. TRIAL DESIGN:
      The EIPS trial is designed as a randomised, equivalence trial between two
      treatment arms. STUDY SETTING: The study was conducted at the paediatric cardiac
      intensive care unit (PCICU) at Aga Khan University Hospital, Karachi.
      PARTICIPANTS: 41 patients (aged 1 month to 15 years) who were admitted to PCICU
      post cardiac surgery were recruited (23 IVPR arm and 18 EPR arm). INTERVENTION:
      Intervention arms were block randomised on alternate weeks for IVPR and EPR.
      OUTCOME MEASURE: Change in serum potassium levels in (mmol/L) and percentage
      change after each event of potassium replacement by the intravenous or enteral
      route. RESULTS: Both groups (41 patients) had similar baseline characteristics.
      Mean age was 4.7 (SD+/-4) years while the most common surgical procedure was
      ventricular septal defect repair (12 patients, 29.3%). No mortality was observed
      in either arm. Four episodes of vomiting and one arrhythmia were seen in the EPR
      group. After adjusting for age, potassium level at the beginning of the episode,
      average urine output, inotropic score and diuretic dose, it was found that there
      was no statistically significant difference in change in potassium levels after
      EPR and IVPR: 0.86 mmol/L (+/-0.8) and 0.82 mmol/L (+/-0.7) respectively (p=0.86,
      95% CI -0.08 to 1.10), or percentage change in potassium level after enteral and
      intravenous replacement: 26% (+/-30) and 24% (+/-20) (95% CI -3.42 to 4.03,
      p=0.87). CONCLUSION: EPR may be an equally efficacious alternative first-line
      therapy in treating hypokalaemia after surgery in selective patients with
      congenital heart disease. ETHICS AND DISSEMINATION: This study has been approved
      by Ethics Review Committee at AKU. TRIAL REGISTRATION NUMBER: NCT02015962.

PMID- 28495811
TI  - Randomised controlled trial of online continuing education for health
      professionals to improve the management of chronic fatigue syndrome: a study
      protocol.
AB  - INTRODUCTION: Chronic fatigue syndrome (CFS) is a serious and debilitating
      illness that affects between 0.2%-2.6% of the world's population. Although there
      is level 1 evidence of the benefit of cognitive behaviour therapy (CBT) and
      graded exercise therapy (GET) for some people with CFS, uptake of these
      interventions is low or at best untimely. This can be partly attributed to poor
      clinician awareness and knowledge of CFS and related CBT and GET interventions.
      This trial aims to evaluate the effect of participation in an online education
      programme, compared with a wait-list control group, on allied health
      professionals' knowledge about evidence-based CFS interventions and their levels
      of confidence to engage in the dissemination of these interventions. METHODS AND
      ANALYSIS: A randomised controlled trial consisting of 180 consenting allied
      health professionals will be conducted. Participants will be randomised into an
      intervention group (n=90) that will receive access to the online education
      programme, or a wait-list control group (n=90). The primary outcomes will be: 1)
      knowledge and clinical reasoning skills regarding CFS and its management,
      measured at baseline, postintervention and follow-up, and 2) self-reported
      confidence in knowledge and clinical reasoning skills related to CFS. Secondary
      outcomes include retention of knowledge and satisfaction with the online
      education programme. The influence of the education programme on clinical
      practice behaviour, and self-reported success in the management of people with
      CFS, will also be assessed in a cohort study design with participants from the
      intervention and control groups combined. ETHICS AND DISSEMINATION: The study
      protocol has been approved by the Human Research Ethics Committee at The
      University of New South Wales (approval number HC16419). Results will be
      disseminated via peer-reviewed journal articles and presentations at scientific
      conferences and meetings. TRIAL REGISTRATION: ACTRN12616000296437.

PMID- 28495803
TI  - On the Run for Hippocampal Plasticity.
AB  - Accumulating research in rodents and humans indicates that exercise benefits
      brain function and may prevent or delay onset of neurodegenerative conditions. In
      particular, exercise modifies the structure and function of the hippocampus, a
      brain area important for learning and memory. This review addresses the central
      and peripheral mechanisms underlying the beneficial effects of exercise on the
      hippocampus. We focus on running-induced changes in adult hippocampal
      neurogenesis, neural circuitry, neurotrophins, synaptic plasticity,
      neurotransmitters, and vasculature. The role of peripheral factors in hippocampal
      plasticity is also highlighted. We discuss recent evidence that systemic factors
      released from peripheral organs such as muscle (myokines), liver (hepatokines),
      and adipose tissue (adipokines) during exercise contribute to hippocampal
      neurotrophin and neurogenesis levels, and memory function. A comprehensive
      understanding of the body-brain axis is needed to elucidate how exercise improves
      hippocampal plasticity and cognition.

PMID- 28495812
TI  - Value of pulmonary artery pressure in predicting in-hospital and one-year
      mortality after valve replacement surgery in middle-aged and aged patients with
      rheumatic mitral disease: an observational study.
AB  - OBJECTIVES: To investigate the role of pulmonary artery pressure (PAP) in
      predicting in-hospital death after valve replacement surgery in middle-aged and
      aged patients with rheumatic mitral disease. DESIGN: An observational study.
      SETTING: Guangdong General Hospital, China. PARTICIPANTS: 1639middle-aged and
      aged patients (mean age 57+/-6 years) diagnosed with rheumatic mitral disease,
      undergoing valve replacement surgery and receiving coronary angiography and
      transthoracic echocardiography before operation, were enrolled. INTERVENTIONS:
      All participants underwent valve replacement surgery and received coronary
      angiography before operation. PRIMARY AND SECONDARY OUTCOME MEASURES: In-hospital
      death and 1-year mortality after operation. METHODS: Included patients were
      divided into four groups based on the preoperative PAP obtained by
      echocardiography: group A (PAP<=30 mm Hg); group B (>30 mm Hg<PAP<=50 mm Hg),
      group C (>50 mm Hg<PAP<=70 mm Hg) and group D (PAP>70 mm Hg). The relationship
      between PAP and in-hospital death and cumulative rate of 1-year mortality was
      evaluated. RESULTS: In-hospital mortality rate increased gradually but
      significantly as the PAP level increased, with 1.9% in group A (n=268), 2.3% in
      group B (n=771), 4.7% in group C (n=384) and 10.2% in group D (n=216) (p<0.001).
      Multivariate analysis showed that PAP>70 mm Hg was an independent predictor of in
      hospital death (OR=2.93, 95% CI 1.61 to 5.32, p<0.001). PAP>52.5 mm Hg had a
      sensitivity of 60.3% and specificity of 67.7% in predicting in-hospital death
      (area under the curve=0.672, 95% CI 0.602 to 0.743, p<0.001). Kaplan-Meier
      analysis showed that patients with PAP>52.5 mm Hg had higher 1-year mortality
      after operation than those without (log-rank=21.51, p<0.001). CONCLUSIONS: PAP
      could serve as a predictor of postoperative in-hospital and 1-year mortality
      after valve replacement surgery in middle-aged and aged patients with rheumatic
      mitral disease.

PMID- 28495813
TI  - Trends in the supply of California's emergency departments and inpatient
      services, 2005-2014: a retrospective analysis.
AB  - OBJECTIVES: Given increasing demand for emergency care, there is growing concern
      over the availability of emergency department (ED) and inpatient resources.
      Existing studies of ED bed supply are dated and often overlook hospital capacity
      beyond ED settings. We described recent statewide trends in the capacity of ED
      and inpatient hospital services from 2005 to 2014. DESIGN: Retrospective
      analysis. SETTING: Using California hospital data, we examined the absolute and
      per admission changes in ED beds and inpatient beds in all hospitals from 2005 to
      2014. PARTICIPANTS: Our sample consisted of all patients inpatient and
      outpatient) from 501 hospital facilities over 10-year period. OUTCOME MEASURES:
      We analysed linear trends in the total annual ED visits, ED beds, licensed and
      staffed inpatient hospital beds and bed types, ED beds per ED visit, and
      inpatient beds per admission (ED and non-ED). RESULTS: Between 2005 and 2014, ED
      visits increased from 9.8 million to 13.2 million (an increase of 35.0%,
      p<0.001). ED beds also increased (by 29.8%, p<0.001), with an average annual
      increase of 195.4 beds. Despite this growth, ED beds per visit decreased by 3.9%,
      from 6.0 ED beds per 10 000 ED visits in 2005 to 5.8 beds in 2014 (p=0.01). While
      overall admission numbers declined by 4.9% (p=0.06), inpatient medical/surgical
      beds per visit grew by 11.3%, from 11.6 medical/surgical beds per 1000 admissions
      in 2005 to 12.9 beds in 2014 (p<0.001). However, there were reductions in
      psychiatric and chemical dependency beds per admission, by -15.3% (p<0.001) and 
      22.4% (p=0.05), respectively. CONCLUSIONS: These trends suggest that, in its
      current state, inadequate supply of ED and specific inpatient beds cannot keep
      pace with growing patient demand for acute care. Analysis of ED and inpatient
      supply should capture dynamic variations in patient demand. Our novel 'beds
      pervisit' metric offers improvements over traditional supply measures.

PMID- 28495814
TI  - Automated control of mechanical ventilation during general anaesthesia: study
      protocol of a bicentric observational study (AVAS).
AB  - INTRODUCTION: Automated control of mechanical ventilation during general
      anaesthesia is not common. A novel system for automated control of most of the
      ventilator settings was designed and is available on an anaesthesia machine.
      METHODS AND ANALYSIS: The 'Automated control of mechanical ventilation during
      general anesthesia study' (AVAS) is an international investigator-initiated
      bicentric observational study designed to examine safety and efficacy of the
      system during general anaesthesia. The system controls mechanical breathing
      frequency, inspiratory pressure, pressure support, inspiratory time and trigger
      sensitivity with the aim to keep a patient stable in user adoptable target zones.
      Adult patients, who are classified as American Society of Anesthesiologists
      physical status I, II or III, scheduled for elective surgery of the upper or
      lower limb or for peripheral vascular surgery in general anaesthesia without any
      additional regional anaesthesia technique and who gave written consent for study
      participation are eligible for study inclusion. Primary endpoint of the study is
      the frequency of specifically defined adverse events. Secondary endpoints are
      frequency of normoventilation, hypoventilation and hyperventilation, the time
      period between switch from controlled ventilation to assisted ventilation,
      achievement of stable assisted ventilation of the patient, proportion of time
      within the target zone for tidal volume, end-tidal partial pressure of carbon
      dioxide as individually set up for each patient by the user, frequency of alarms,
      frequency distribution of tidal volume, inspiratory pressure, inspiration time,
      expiration time, end-tidal partial pressure of carbon dioxide and the number of
      re-intubations. ETHICS AND DISSEMINATION: AVAS will be the first clinical study
      investigating a novel automated system for the control of mechanical ventilation
      on an anaesthesia machine. The study was approved by the ethics committees of
      both participating study sites. In case that safety and efficacy are acceptable,
      a randomised controlled trial comparing the novel system with the usual practice
      may be warranted. TRIAL REGISTRATION: DRKS DRKS00011025, registered 12 October
      2016; clinicaltrials.gov ID. NCT02644005, registered 30 December 2015.

PMID- 28495815
TI  - Understanding the implementation and adoption of an information technology
      intervention to support medicine optimisation in primary care: qualitative study
      using strong structuration theory.
AB  - OBJECTIVES: Using strong structuration theory, we aimed to understand the
      adoption and implementation of an electronic clinical audit and feedback tool to
      support medicine optimisation for patients in primary care. DESIGN: This is a
      qualitative study informed by strong structuration theory. The analysis was
      thematic, using a template approach. An a priori set of thematic codes, based on
      strong structuration theory, was developed from the literature and applied to the
      transcripts. The coding template was then modified through successive readings of
      the data. SETTING: Clinical commissioning group in the south of England.
      PARTICIPANTS: Four focus groups and five semi-structured interviews were
      conducted with 18 participants purposively sampled from a range of stakeholder
      groups (general practitioners, pharmacists, patients and commissioners). RESULTS:
      Using the system could lead to improved medication safety, but use was determined
      by broad institutional contexts; by the perceptions, dispositions and skills of
      users; and by the structures embedded within the technology. These included
      perceptions of the system as new and requiring technical competence and skill;
      the adoption of the system for information gathering; and interactions and
      relationships that involved individual, shared or collective use. The dynamics
      between these external, internal and technological structures affected the
      adoption and implementation of the system. CONCLUSIONS: Successful implementation
      of information technology interventions for medicine optimisation will depend on
      a combination of the infrastructure within primary care, social structures
      embedded in the technology and the conventions, norms and dispositions of those
      utilising it. Future interventions, using electronic audit and feedback tools to
      improve medication safety, should consider the complexity of the social and
      organisational contexts and how internal and external structures can affect the
      use of the technology in order to support effective implementation.

PMID- 28495816
TI  - Determinants of treatment duration in the prevention of recurrent venous
      thromboembolism: a protocol for a balanced vignette experiment.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is a condition that annually occurs in
      approximately 10/00 of the world's population. Patients who have already had a
      VTE are at elevated risk for a recurrent VTE. Recurrent events increase the risk
      of long-term sequelae and can be fatal. Adequate secondary prophylaxis is thus
      needed to prevent such events. Patients with VTE are often prone to bleeding, and
      pharmacological prophylaxis exacerbates bleeding risk. Expert opinions on the
      optimum duration of secondary prophylaxis in VTE still vary substantially. The
      existence of treatment guidelines has not led to uniformity of VTE secondary
      prophylaxis strategies, which means that physicians still adhere to individual
      risk calculi in determining treatment duration. METHODS AND ANALYSIS: The aim of
      this study is to establish what factors lie at the root of this variance in VTE
      secondary prophylactic treatment strategies, and what risk factors are deemed of
      particular importance in determining the perceived risks and benefits of variable
      treatment durations. To do this, we created a survey based on a D-efficient and G
      efficient balanced experimental vignette design. This protocol covers all aspects
      of how this survey was set up and how it was implemented. The analysis of the
      experimental data will be carried out using mixed-effects methods, which are
      beneficial in scenarios with high interindividual variance and correlated (eg,
      repeated-measures) responses. We propose the use of maximal random effects
      structures insofar as possible. ETHICS AND DISSEMINATION: All data are de
      identified, and any identifying characteristics of the respondents will not be
      reported in a final manuscript or elsewhere. A paper describing the expert
      interviews is currently under peer review. A manuscript that contains the
      analysis of the results of the experiment described in this protocol is being
      drafted, and will also be submitted to a peer-reviewed journal.

PMID- 28495817
TI  - Estimating the prevalence, hospitalisation and mortality from type 2 diabetes
      mellitus in Nigeria: a systematic review and meta-analysis.
AB  - BACKGROUND: There is not yet a comprehensive evidence-based epidemiological
      report on type 2 diabetes mellitus (T2DM) in Nigeria. We aimed to estimate
      country-wide and zonal prevalence, hospitalisation and mortality rates of T2DM in
      Nigeria. METHODS: We searched MEDLINE, EMBASE, Global Health, Africa Journals
      Online (AJOL) and Google Scholar for population and hospital-based studies on
      T2DM in Nigeria. We conducted a random-effects meta-analysis on extracted crude
      estimates, and applied a meta-regression epidemiological model, using the United
      Nations demographics for Nigeria in 1990 and 2015 to determine estimates of
      diabetes in Nigeria for the two years. RESULTS: 42 studies, with a total
      population of 91 320, met our selection criteria. Most of the studies selected
      were of medium quality (90.5%). The age-adjusted prevalence rates of T2DM in
      Nigeria among persons aged 20-79 years increased from 2.0% (95% CI 1.9% to 2.1%)
      in 1990 to 5.7% (95% CI 5.5% to 5.8%) in 2015, accounting for over 874 000 and
      4.7 million cases, respectively. The pooled prevalence rate of impaired glucose
      tolerance was 10.0% (95% CI 4.5% to 15.6%), while impaired fasting glucose was
      5.8% (95% CI 3.8% to 7.8%). Hospital admission rate for T2DM was 222.6 (95% CI
      133.1 to 312.1) per 100 000 population with hyperglycaemic emergencies, diabetic
      foot and cardiovascular diseases being most common complications. The overall
      mortality rate was 30.2 (95% CI 14.6 to 45.8) per 100 000 population, with a case
      fatality rate of 22.0% (95% CI 8.0% to 36.0%). CONCLUSION: Our findings suggest
      an increasing burden of T2DM in Nigeria with many persons currently undiagnosed,
      and few known cases on treatment.

PMID- 28495820
TI  - Next government must tackle public health "ticking time bomb," says BMA.

PMID- 28495821
TI  - How to Image Repaired Tetralogy of Fallot.

PMID- 28495818
TI  - Application of minimal important differences in degenerative knee disease
      outcomes: a systematic review and case study to inform BMJ Rapid Recommendations.
AB  - OBJECTIVES: To identify the most credible anchor-based minimal important
      differences (MIDs) for patient important outcomes in patients with degenerative
      knee disease, and to inform BMJ Rapid Recommendations for arthroscopic surgery
      versus conservative management DESIGN: Systematic review. OUTCOME MEASURES:
      Estimates of anchor-based MIDs, and their credibility, for knee symptoms and
      health-related quality of life (HRQoL). DATA SOURCES: MEDLINE, EMBASE and
      PsycINFO. ELIGIBILITY CRITERIA: We included original studies documenting the
      development of anchor-based MIDs for patient-reported outcomes (PROs) reported in
      randomised controlled trials included in the linked systematic review and meta
      analysis and judged by the parallel BMJ Rapid Recommendations panel as critically
      important for informing their recommendation: measures of pain, function and
      HRQoL. RESULTS: 13 studies reported 95 empirically estimated anchor-based MIDs
      for 8 PRO instruments and/or their subdomains that measure knee pain, function or
      HRQoL. All studies used a transition rating (global rating of change) as the
      anchor to ascertain the MID. Among PROs with more than 1 estimated MID, we found
      wide variation in MID values. Many studies suffered from serious methodological
      limitations. We identified the following most credible MIDs: Western Ontario and
      McMaster University Osteoarthritis Index (WOMAC; pain: 12, function: 13), Knee
      injury and Osteoarthritis Outcome Score (KOOS; pain: 12, activities of daily
      living: 8) and EuroQol five dimensions Questionnaire (EQ-5D; 0.15). CONCLUSIONS:
      We were able to distinguish between more and less credible MID estimates and
      provide best estimates for key instruments that informed evidence presentation in
      the associated systematic review and judgements made by the Rapid Recommendation
      panel. TRIAL REGISTRATION NUMBER: CRD42016047912.

PMID- 28495819
TI  - Knee arthroscopy versus conservative management in patients with degenerative
      knee disease: a systematic review.
AB  - OBJECTIVE: To determine the effects and complications of arthroscopic surgery
      compared with conservative management strategies in patients with degenerative
      knee disease. DESIGN: Systematic review. MAIN OUTCOME MEASURES: Pain, function,
      adverse events. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of
      Controlled Trials (CENTRAL), Google Scholar and Open Grey up to August 2016.
      ELIGIBILITY CRITERIA: For effects, randomised clinical trials (RCTs) comparing
      arthroscopic surgery with a conservative management strategy (including sham
      surgery) in patients with degenerative knee disease. For complications, RCTs and
      observational studies. REVIEW METHODS: Two reviewers independently extracted data
      and assessed risk of bias for patient-important outcomes. A parallel guideline
      committee (BMJ Rapid Recommendations) provided input on the design and
      interpretation of the systematic review, including selection of patient-important
      outcomes. We used the GRADE approach to rate the certainty (quality) of the
      evidence. RESULTS: We included 13 RCTs and 12 observational studies. With respect
      to pain, the review identified high-certainty evidence that knee arthroscopy
      results in a very small reduction in pain up to 3 months (mean difference =5.4 on
      a 100-point scale, 95% CI 2.0 to 8.8) and very small or no pain reduction up to 2
      years (mean difference =3.1, 95% CI -0.2 to 6.4) when compared with conservative
      management. With respect to function, the review identified moderate-certainty
      evidence that knee arthroscopy results in a very small improvement in the short
      term (mean difference =4.9 on a 100-point scale, 95% CI 1.5 to 8.4) and very
      small or no improved function up to 2 years (mean difference =3.2, 95% CI -0.5 to
      6.8). Alternative presentations of magnitude of effect, and associated
      sensitivity analyses, were consistent with the findings of the primary analysis.
      Low-quality evidence suggested a very low probability of serious complications
      after knee arthroscopy. CONCLUSIONS: Over the long term, patients who undergo
      knee arthroscopy versus those who receive conservative management strategies do
      not have important benefits in pain or function. TRIAL REGISTRATION NUMBER:
      PROSPERO CRD42016046242.

PMID- 28495822
TI  - How to Image Congenital Left Heart Obstruction in Adults.

PMID- 28495823
TI  - How to Image the Adult Patient With Fontan Circulation.

PMID- 28495825
TI  - Congenital Heart Disease: Multimodal Imaging Is Every Day's Routine.

PMID- 28495824
TI  - How to Image the Dilated Right Ventricle.

PMID- 28495826
TI  - Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population
      and Association With Risk for Recurrent Stroke.
AB  - BACKGROUND AND PURPOSE: von Willebrand factor (vWF) plays an important role in
      thrombus formation during cerebrovascular damage. We sought to investigate the
      potential role of circulating vWF in recurrent cerebrovascular events and
      identify genetic contributors to variation in vWF level in an ischemic stroke
      population. METHODS: We analyzed the effect of circulating vWF on risk of
      recurrent stroke using survival models in the VISP trial (Vitamin Intervention
      for Stroke Prevention) and the use of vWF in reclassification over traditional
      factors. We conducted a genome-wide association study) with imputation, based on
      1000 Genomes Project data, for circulating vWF levels and then interrogated loci
      previously associated with vWF levels. We performed expression quantitative trait
      locus analysis for vWF across different tissues. RESULTS: Elevated vWF levels
      were associated with increased risk for recurrent stroke in VISP. Adding vWF to
      traditional clinical parameters also improved recurrent stroke risk prediction.
      We identified single-nucleotide polymorphisms significantly associated with
      circulating vWF at the ABO locus (P<5*10-8) and replicated findings from previous
      genetic associations of vWF levels in humans. Expression quantitative trait locus
      analyses demonstrate that most associated ABO single-nucleotide polymorphisms
      were also associated with vWF gene expression. CONCLUSIONS: Elevated vWF levels
      are associated with recurrent stroke in VISP. In the VISP population, genetic
      determinants of vWF levels that impact vWF gene expression were identified. These
      data add to our knowledge of the pathophysiologic and genetic basis for recurrent
      stroke risk and may have implications for clinical care decision making.

PMID- 28495828
TI  - Letter by McGowan Regarding Article, "Quality of Acute Care and Long-Term Quality
      of Life and Survival: The Australian Stroke Clinical Registry".

PMID- 28495827
TI  - Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation
      Through ATP/NAD+/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion
      Rats.
AB  - BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell
      death and brain dysfunction after ischemic stroke. In this study, we investigated
      whether energy depletion is involved in hyperglycemia-induced hemorrhagic
      transformation after ischemic stroke and determined the pathway underlying the
      beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle
      cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6
      mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats
      were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor
      oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent
      mating type information regulation 2 homolog 1 siRNA was administrated for
      interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits
      were recorded; the level of blood glucose, ATP, and nicotinamide adenine
      dinucleotide and the activity of nicotinamide phosphoribosyl transferase were
      monitored; the expression of silent mating type information regulation 2 homolog
      1, acetylated p53, acetylated nuclear factor-kappaB, and cleaved caspase 3 were
      detected by Western blots; and the activity of matrix metalloproteinase-9 was
      assayed by zymography. RESULTS: Hyperglycemia deteriorated energy metabolism and
      reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated
      hemorrhagic transformation, blood-brain barrier disruption, and neurological
      deficits after middle cerebral artery occlusion. HBO treatment increased the
      levels of the ATP and nicotinamide adenine dinucleotide and consequently
      increased silent mating type information regulation 2 homolog 1, resulting in
      attenuation of hemorrhagic transformation, brain infarction, as well as
      improvement of neurological function in hyperglycemic middle cerebral artery
      occlusion rats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine
      dinucleotide/silent mating type information regulation 2 homolog 1 pathway and
      protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion
      rats. HBO might be promising approach for treatment of acute ischemic stroke
      patients, especially patients with diabetes mellitus or treated with r-tPA
      (recombinant tissue-type plasminogen activator).

PMID- 28495829
TI  - Association Between Brain-Derived Neurotrophic Factor Genotype and Upper
      Extremity Motor Outcome After Stroke.
AB  - BACKGROUND AND PURPOSE: The identification of intrinsic factors for predicting
      upper extremity motor outcome could aid the design of individualized treatment
      plans in stroke rehabilitation. The aim of this study was to identify prognostic
      factors, including intrinsic genetic factors, for upper extremity motor outcome
      in patients with subacute stroke. METHODS: A total of 97 patients with subacute
      stroke were enrolled. Upper limb motor impairment was scored according to the
      upper limb of Fugl-Meyer assessment score at 3 months after stroke. The
      prediction of upper extremity motor outcome at 3 months was modeled using various
      factors that could potentially influence this impairment, including patient
      characteristics, baseline upper extremity motor impairment, functional and
      structural integrity of the corticospinal tract, and brain-derived neurotrophic
      factor genotype. Multivariate ordinal logistic regression models were used to
      identify the significance of each factor. RESULTS: The independent predictors of
      motor outcome at 3 months were baseline upper extremity motor impairment, age,
      stroke type, and corticospinal tract functional integrity in all stroke patients.
      However, in the group with severe motor impairment at baseline (upper limb score
      of Fugl-Meyer assessment <25), the number of Met alleles in the brain-derived
      neurotrophic factor genotype was also an independent predictor of upper extremity
      motor outcome 3 months after stroke. CONCLUSIONS: Brain-derived neurotrophic
      factor genotype may be a potentially useful predictor of upper extremity motor
      outcome in patients with subacute stroke with severe baseline motor involvement.

PMID- 28495830
TI  - Establishing Recommendations for Stroke Systems in the Thrombectomy Era: The
      Upstate New York Stakeholder Proceedings.
AB  - BACKGROUND AND PURPOSE: The American Heart Association/American Stroke
      Association and Department of Health Stroke Coverdell Program convened a
      stakeholder meeting in upstate NY to develop recommendations to enhance stroke
      systems for acute large vessel occlusion. METHODS: Prehospital, hospital, and
      Department of Health leadership were invited (n=157). Participants provided
      goals/concerns and developed recommendations for prehospital triage and
      interfacility transport, rating each using a 3-level impact (A [high], B, and C
      [low]) and implementation feasibility (1 [high], 2, and 3 [low]) scale. Six weeks
      later, participants finalized recommendations. RESULTS: Seventy-one stakeholders
      (45% of invitees) attended. Six themes around goals/concerns emerged: (1)
      emergency medical services capacity, (2) validated prehospital screening tools,
      (3) facility capability, (4) triage/transport guidelines, (5) data
      capture/feedback tools, and (6) facility competition. In response, high-impact
      (level A) prehospital recommendations, stratified by implementation feasibility,
      were (1) use of online medical control for triage (6%); (2) regional
      transportation strategy (31%), standardized emergency medical services checklists
      (18%), quality metrics (14%), standardized prehospital screening tools (13%), and
      feedback for performance improvement (7%); and (3) smartphone application
      algorithm for screening/decision-making (6%) and ambulance-based telemedicine
      (6%). Level A interfacility transfer recommendations were (1) standardized
      transfer process (32%)/timing goals (16%)/regionalized systems (11%), performance
      metrics (11%), image sharing capabilities (7%); (2) provider education (9%) and
      stroke toolbox (5%); and (3) interfacility telemedicine (7%) and feedback (2%).
      CONCLUSIONS: The methods used and recommendations generated provide models for
      stroke system enhancement. Implementation may vary based on geographic
      need/capacity and be contingent on establishing standard care practices. Further
      research is needed to establish optimal implementation strategies.

PMID- 28495833
TI  - Dequalinium for bacterial vaginosis.
AB  - Bacterial vaginosis is an infection characterised by overgrowth of anaerobic
      bacteria in the vagina with an accompanying loss of lactobacilli, and is thought
      to be the most common cause of abnormal vaginal discharge in women of child
      bearing age.1 Standard treatment for symptomatic bacterial vaginosis consists of
      a short course of an oral or topical antibiotic.2 Dequalinium, a topical
      antiseptic agent, has been available for many years as a treatment for oral
      infections.3 A new formulation, dequalinium 10mg vaginal tablets (Fluomizin-Kora
      Healthcare), was licensed in the UK in June 2015 for the treatment of bacterial
      vaginosis.4 Here, we review evidence for the effectiveness and safety of
      dequalinium vaginal tablets in the management of bacterial vaginosis.

PMID- 28495831
TI  - Clinical Correlates, Ethnic Differences, and Prognostic Implications of
      Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Perivascular spaces (PVSs) are considered markers of
      small vessel disease. However, their long-term prognostic implications in
      transient ischemic attack/ischemic stroke patients are unknown. Ethnic
      differences in PVS prevalence are also unknown. METHODS: Two independent
      prospective studies were conducted, 1 comprising predominantly whites with
      transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1
      comprising predominantly Chinese with ischemic stroke (University of Hong Kong).
      Clinical and imaging correlates, prognostic implications for stroke and death,
      and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were
      studied with adjustment for age, sex, vascular risk factors, and scanner
      strength. RESULTS: Whites with transient ischemic attack/ischemic stroke (n=1028)
      had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20
      BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than
      20 BG or CS-PVSs were both associated with increasing age and white matter
      hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001).
      During 6924 patient-years of follow-up, BG-PVSs were also independently
      associated with an increased risk of recurrent ischemic stroke (adjusted hazard
      ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78
      1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P=0.011) but not intracerebral hemorrhage
      (P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with
      recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were
      similar in both cohorts. CONCLUSIONS: Over and above ethnic differences in
      frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and
      CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with
      an increased risk of recurrent ischemic stroke, CS-PVSs were not.

PMID- 28495834
TI  - Testosterone therapy for menopausal women.
AB  - It has been suggested that there is a link between low circulating concentrations
      of testosterone and reduced sexual functioning in postmenopausal women,1 and it
      has been more than 60 years since the effects of testosterone therapy for the
      management of menopausal symptoms were first reported.2 Since then, testosterone
      supplementation has received growing attention for its potential role in
      maintaining sexual function in menopausal women. The National Institute for
      Health and Care Excellence guideline on the diagnosis and management of menopause
      recommends considering testosterone supplementation for women with low sexual
      desire if hormone replacement therapy (HRT) alone has been ineffective.3 However,
      in the UK no testosterone products are licensed for such use. A testosterone
      patch authorised by the European Medicines Agency in 2006 for use in women with
      surgical menopause was withdrawn from the market in 2012 for commercial reasons.4
      Here, we provide an update on the evidence of the effectiveness and safety of
      testosterone supplementation in menopausal women.

PMID- 28495835
TI  - UK poverty has "devastating" effect on children's health, doctors warn.

PMID- 28495836
TI  - Spatial regulation of organelle release from myosin V transport by p21-activated
      kinases.
AB  - Correct positioning of organelles is essential to eukaryotic cells. Molecular
      motors transport organelles to their proper destinations, yet little is known
      about the pathways that define these destinations. In Saccharomyces cerevisiae,
      the myosin V motor Myo2 binds the vacuole-specific adapter Vac17 to attach to the
      vacuole/lysosome and initiate transport. After arrival in the bud, Myo2 releases
      the vacuole, and Vac17 is degraded. However, the mechanisms that spatially
      regulate this release were not established. In this study, we report that the bud
      cortex is a landmark that signals a successful delivery of the vacuole to the
      bud. We demonstrate that upon arrival at the bud cortex, Vac17 is phosphorylated
      by Cla4. Cla4-dependent phosphorylation is required for the ubiquitylation and
      subsequent degradation of Vac17 and the release of the vacuole from Myo2. Our
      study reveals a critical step in the spatial regulation of myosin V-dependent
      organelle transport and may reveal common mechanisms for how molecular motors
      accurately deposit cargoes at the correct locations.

PMID- 28495837
TI  - Congressing kinetochores progressively load Ska complexes to prevent force
      dependent detachment.
AB  - Kinetochores mediate chromosome congression by either sliding along the lattice
      of spindle microtubules or forming end-on attachments to their depolymerizing
      plus-ends. By following the fates of individual kinetochores as they congress in
      live cells, we reveal that the Ska complex is required for a distinct substep of
      the depolymerization-coupled pulling mechanism. Ska depletion increases the
      frequency of naturally occurring, force-dependent P kinetochore detachment
      events, while being dispensable for the initial biorientation and movement of
      chromosomes. In unperturbed cells, these release events are followed by
      reattachment and successful congression, whereas in Ska-depleted cells, detached
      kinetochores remain in a futile reattachment/detachment cycle that prevents
      congression. We further find that Ska is progressively loaded onto bioriented
      kinetochore pairs as they congress. We thus propose a model in which kinetochores
      mature through Ska complex recruitment and that this is required for improved
      load-bearing capacity and silencing of the spindle assembly checkpoint.

PMID- 28495839
TI  - Medical residents' interest in and current status of Japanese postgraduate
      education in acupuncture and moxibustion: a follow-up survey.
AB  - BACKGROUND: Japanese traditional medicine (Kampo medicine) is an important
      subject in Japanese medical schools. Acupuncture and moxibustion (AM), essential
      categories of Kampo medicine, are taught in a few medical schools today. However,
      the current state of postgraduate AM education is unknown. OBJECTIVE: To compare
      medical residents' awareness of AM before their AM education in the 4th year of
      medical school with that after completion of their 2-year postgraduate medical
      residency. METHODS: We conducted a postal questionnaire survey of medical
      residents at the end of their 2-year residency. We required a signature on this
      questionnaire so that we could examine for changes in their awareness of AM with
      those determined by similar, signed, former questionnaire surveys conducted
      before and at the end of their 4th-year AM lectures in medical school (reported
      previously). The completed questionnaires were returned by mail or facsimile.
      RESULTS: Among 93 residents, there were 72 (77.4%) effective responses. Only
      three residents (4%) had opportunities to learn AM during residency. Among the 68
      residents who were not afforded the opportunity to do so, after completing their
      two-year residency, 32(47%) stated that they would like to study AM. Interest in
      AM was significantly less than that of the proportion of medical students (81%)
      who were initially interested in AM when surveyed just before their fourth year
      lectures on AM. CONCLUSIONS: Postgraduate AM education for medical residents
      appears to be relatively scarce in Japan. Moreover, medical residents' levels of
      interest in AM were lower than those demonstrated before their 4th-year AM
      lectures in medical school.

PMID- 28495838
TI  - Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment.
AB  - Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how
      mutations in USH1 genes lead to retinal dystrophy in patients remains elusive.
      The USH1 protein complex is associated with calyceal processes, which are
      microvilli of unknown function surrounding the base of the photoreceptor outer
      segment. We show that in Xenopus tropicalis, these processes are connected to the
      outer-segment membrane by links composed of protocadherin-15 (USH1F protein).
      Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired
      photoreceptor function and abnormally shaped photoreceptor outer segments. Rod
      basal outer disks displayed excessive outgrowth, and cone outer segments were
      curved, with lamellae of heterogeneous sizes, defects also observed upon
      knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes
      were virtually absent in cones and displayed markedly reduced F-actin content in
      rods, suggesting that protocadherin-15-containing links are essential for their
      development and/or maintenance. We propose that calyceal processes, together with
      their associated links, control the sizing of rod disks and cone lamellae
      throughout their daily renewal.

PMID- 28495840
TI  - Nonlinearities of heart rate variability in animal models of impaired cardiac
      control: contribution of different time scales.
AB  - Heart rate variability (HRV) has been extensively explored by traditional linear
      approaches (e.g., spectral analysis); however, several studies have pointed to
      the presence of nonlinear features in HRV, suggesting that linear tools might
      fail to account for the complexity of the HRV dynamics. Even though the prevalent
      notion is that HRV is nonlinear, the actual presence of nonlinear features is
      rarely verified. In this study, the presence of nonlinear dynamics was checked as
      a function of time scales in three experimental models of rats with different
      impairment of the cardiac control: namely, rats with heart failure (HF),
      spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats.
      Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating
      statistic for the surrogate test utilized to detect nonlinearity. Nonlinear
      dynamics is less present in HF animals at both short and long time scales
      compared with controls. A similar finding was found in SHR only at short time
      scales. SAD increased the presence of nonlinear dynamics exclusively at short
      time scales. Those findings suggest that a working baroreflex contributes to
      linearize HRV and to reduce the likelihood to observe nonlinear components of the
      cardiac control at short time scales. In addition, an increased sympathetic
      modulation seems to be a source of nonlinear dynamics at long time scales.
      Testing nonlinear dynamics as a function of the time scales can provide a
      characterization of the cardiac control complementary to more traditional markers
      in time, frequency, and information domains.NEW & NOTEWORTHY Although heart rate
      variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests
      are rarely used to check this hypothesis. By adopting multiscale entropy (MSE)
      and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test,
      we show that nonlinear dynamics varies with time scale and the type of cardiac
      dysfunction. Moreover, as complexity metrics and nonlinearities provide
      complementary information, we strongly recommend using the test for nonlinearity
      as an additional index to characterize HRV.

PMID- 28495841
TI  - Lower-body negative pressure decreases noninvasively measured intracranial
      pressure and internal jugular vein cross-sectional area during head-down tilt.
AB  - Long-term spaceflight induces a near visual acuity change in ~50% of astronauts.
      In some crew members, postflight cerebrospinal fluid (CSF) opening pressures by
      lumbar puncture are as high as 20.9 mmHg; these members demonstrated optic disc
      edema. CSF communicates through the cochlear aqueduct to affect perilymphatic
      pressure and tympanic membrane motion. We hypothesized that 50 mmHg of lower-body
      negative pressure (LBNP) during 15 degrees  head-down tilt (HDT) would mitigate
      elevations in internal jugular vein cross-sectional area (IJV CSA) and
      intracranial pressure (ICP). Fifteen healthy adult volunteers were positioned in
      sitting (5 min), supine (5 min), 15 degrees  HDT (5 min), and 15 degrees  HDT
      with LBNP (10 min) postures for data collection. Evoked tympanic membrane
      displacements (TMD) quantified ICP noninvasively. IJV CSA was measured using
      standard ultrasound techniques. ICP and IJV CSA increased significantly from the
      seated upright to the 15 degrees  HDT posture (P < 0.05), and LBNP mitigated
      these increases. LBNP at 25 mmHg reduced ICP during HDT (TMD of 322.13 +/- 419.17
      nl) to 232.38 +/- 445.85 nl, and at 50 mmHg ICP was reduced further to TMD of
      199.76 +/- 429.69 nl. In addition, 50 mmHg LBNP significantly reduced IJV CSA
      (1.50 +/- 0.33 cm2) during 15 degrees  HDT to 0.83 +/- 0.42 cm2 LBNP counteracts
      the headward fluid shift elevation of ICP and IJV CSA experienced during
      microgravity as simulated by15 degrees  HDT. These data provide quantitative
      evidence that LBNP shifts cephalic fluid to the lower body, reducing IJV CSA and
      ICP.NEW & NOTEWORTHY The current study provides new evidence that 25 or 50 mmHg
      of lower body negative pressure reduces jugular venous pooling and intracranial
      pressure during simulated microgravity. Therefore, spaceflight countermeasures
      that sequester fluid to the lower body may mitigate cephalic venous congestion
      and vision impairment.

PMID- 28495844
TI  - Molecular imaging of postprandial metabolism.
AB  - Disordered postprandial metabolism of energy substrates is one of the main
      defining features of prediabetes and contributes to the development of several
      chronic diseases associated with obesity, such as type 2 diabetes and
      cardiovascular diseases. Postprandial energy metabolism has been studied using
      classical isotopic tracer approaches that are limited by poor access to
      splanchnic metabolism and highly dynamic and complex exchanges of energy
      substrates involving multiple organs and systems. Advances in noninvasive
      molecular imaging modalities, such as PET and MRI/magnetic resonance spectroscopy
      (MRS), have recently allowed important advances in our understanding of
      postprandial energy metabolism in humans. The present review describes some of
      these recent advances, with particular focus on glucose and fatty acid metabolism
      in the postprandial state, and discusses current gaps in knowledge and new
      perspectives of application of PET and MRI/MRS for the investigation and
      treatment of human metabolic diseases.

PMID- 28495843
TI  - Treating fructose-induced metabolic changes in mice with high-intensity interval
      training: insights in the liver, white adipose tissue, and skeletal muscle.
AB  - Fructose-rich caloric sweeteners induce adverse changes in the metabolism of
      humans. The study evaluated the effects of high-intensity interval training
      (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue
      (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk
      one of the following diets: control (C; 5% of total energy from fructose) or
      fructose (F; 55% of total energy from fructose). In the 10th week, for an
      additional 8-wk period, the groups were divided into nontrained (NT) or HIIT
      groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the
      experiment, fructose consumption in the F-NT group led to a high systolic blood
      pressure, high plasma triglycerides, insulin resistance with glucose intolerance,
      and lower insulin sensitivity. We also observed liver steatosis, adipocyte
      hypertrophy, and diminished gene expressions of peroxisome proliferator-activated
      receptor-gamma coactivator 1-alpha and fibronectin type III domain containing 5
      (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased
      gene expressions of nuclear respiratory factor 1 and mitochondrial transcription
      factor A (markers of mitochondrial biogenesis), and peroxisome proliferator
      activated receptor-alpha and carnitine palmitoyltransferase 1 (markers of beta
      oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In
      conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure,
      glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle
      were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for
      diseases affecting these tissues.NEW & NOTEWORTHY We investigated the effects of
      high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the
      resulting severe negative effect on the liver, white adipose tissue (WAT), and
      skeletal muscle, which reduced the expression of fibronectin type III domain
      containing 5 (FNDC5, irisin) and PGC1alpha and, consequently, affected markers of
      mitochondrial biogenesis and beta-oxidation. Because HIIT may block these adverse
      effects in all of these three tissues, it might be suggested that it functions as
      a coadjutant treatment in combatting the alterations caused by high-fructose
      intake.

PMID- 28495842
TI  - The impact of ocular hemodynamics and intracranial pressure on intraocular
      pressure during acute gravitational changes.
AB  - Exposure to microgravity causes a bulk fluid shift toward the head, with
      concomitant changes in blood volume/pressure, and intraocular pressure (IOP).
      These and other factors, such as intracranial pressure (ICP) changes, are
      suspected to be involved in the degradation of visual function and ocular
      anatomical changes exhibited by some astronauts. This is a significant health
      concern. Here, we describe a lumped-parameter numerical model to simulate
      volume/pressure alterations in the eye during gravitational changes. The model
      includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent
      ocular compliance. It is formulated as a series of coupled differential equations
      and was validated against four existing data sets on parabolic flight, body
      inversion, and head-down tilt (HDT). The model accurately predicted acute IOP
      changes in parabolic flight and HDT, and was satisfactory for the more extreme
      case of inversion. The short-term response to the changing gravitational field
      was dominated by ocular blood pressures and compliance, while longer-term
      responses were more dependent on aqueous humor dynamics. ICP had a negligible
      effect on acute IOP changes. This relatively simple numerical model shows
      promising predictive capability. To extend the model to more chronic conditions,
      additional data on longer-term autoregulation of blood and aqueous humor dynamics
      are needed.NEW & NOTEWORTHY A significant percentage of astronauts present
      anatomical changes in the posterior eye tissues after spaceflight. Hypothesized
      increases in ocular blood volume and intracranial pressure (ICP) in space have
      been considered to be likely factors. In this work, we provide a novel numerical
      model of the eye that incorporates ocular hemodynamics, gravitational forces, and
      ICP changes. We find that changes in ocular hemodynamics govern the response of
      intraocular pressure during acute gravitational change.

PMID- 28495845
TI  - Edmund Goodwyn and the first description of diving bradycardia.
AB  - Diving bradycardia is a primordial oxygen-conserving reflex by which the heart
      rate of air-breathing vertebrates, including humans, slows down in response to
      water immersion. Its discovery is attributed to Paul Bert, whose seminal
      observation was published in 1870 as part of a series of experiments that
      examined physiological adaptations to asphyxia in ducks and other animals.
      However, Edmund Goodwyn, a British physician who studied medicine at the
      University of Edinburgh, had already described this reflex in his doctoral
      thesis, which was originally published in Latin in 1786 and again in English in
      1788. Ironically, even though Goodwyn's work has yet to be recognized in the
      diving physiology literature, it was referenced in the very publication that
      contains Bert's original observation. Thus this article brings Goodwyn's work and
      its historical context to light and argues that he should be credited with the
      first description of diving bradycardia.

PMID- 28495846
TI  - Dispelling the myth that habitual caffeine consumption influences the performance
      response to acute caffeine supplementation.
AB  - This study investigates the influence of habitual caffeine intake on aerobic
      exercise-performance responses to acute caffeine supplementation. A double-blind,
      crossover, counterbalanced study was performed. Forty male endurance-trained
      cyclists were allocated into tertiles, according to their daily caffeine intake:
      low (58 +/- 29 mg/d), moderate (143 +/- 25 mg/d), and high (351 +/- 139 mg/d)
      consumers. Participants completed three trials in which they performed simulated
      cycling time trials (TTs) in the fastest time possible following ingestion of the
      following: caffeine (CAF: 6 mg/kg body mass), placebo (PLA), and no supplement
      (CON). A mixed-model analysis revealed that TT performance was significantly
      improved in CAF compared with PLA and CON (29.92 +/- 2.18 vs. 30.81 +/- 2.67 and
      31.14 +/- 2.71 min, respectively; P = 0.0002). Analysis of covariance revealed no
      influence of habitual caffeine intake as a covariate on exercise performance (P =
      0.47). TT performance was not significantly different among tertiles (P = 0.75).
      No correlation was observed between habitual caffeine intake and absolute changes
      (CAF - CON) in TT performance with caffeine (P = 0.524). Individual analysis
      showed that eight, seven, and five individuals improved above the variation of
      the test in CAF in the low, moderate, and high tertiles, respectively. A Fisher's
      exact test did not show any significant differences in the number of individuals
      who improved in CAF among the tertiles (P > 0.05). Blood lactate and ratings of
      perceived exertion were not different between trials and tertiles (P > 0.05).
      Performance effects of acute caffeine supplementation during an ~30-min cycling
      TT performance were not influenced by the level of habitual caffeine
      consumption.NEW & NOTEWORTHY There has been a long-standing paradigm that
      habitual caffeine intake may influence the ergogenicity of caffeine
      supplementation. Low, moderate, and high caffeine consumers showed similar
      absolute and relative improvements in cycling time-trial performance following
      acute supplementation of 6 mg/kg body mass caffeine. Performance effects of acute
      caffeine were not influenced by the level of habitual caffeine consumption,
      suggesting that high habitual caffeine intake does not negate the benefits of
      acute caffeine supplementation.

PMID- 28495847
TI  - Inflammatory responses to acute elevations of carbon dioxide in mice.
AB  - Health risks are described from elevated indoor air carbon dioxide (CO2), which
      often ranges from 1,000 to 4,000 ppm, but the mechanisms are unknown. Here, we
      demonstrate that mice exposed for 2 h to 2,000 or 4,000 ppm CO2 exhibit,
      respectively, 3.4 +/- 0.9-fold (SE, n = 6) and 4.1 +/- 0.7-fold (n = 10)
      elevations in circulating microparticles (MPs); neutrophil and platelet
      activation, and vascular leak in brain, muscle, and distal colon. Interleukin
      (IL)-1beta content of MPs also increases after 2,000 ppm by 3.8 +/- 0.6-fold (n =
      6) and after 4,000 ppm CO2 by 9.3 +/- 1.1-fold (n = 10) greater than control. CO2
      induced vascular damage is abrogated by treating mice with an antibody to IL
      1beta or an IL-1beta receptor inhibitor. Injecting naive mice with CO2-induced
      MPs expressing a protein found on mature neutrophils recapitulates vascular
      damage as seen with elevated CO2, and destruction of MPs in CO2-exposed mice
      abrogates vascular injuries without altering neutrophil or platelet activation.
      We conclude that environmentally relevant elevations of CO2 trigger neutrophils
      to generate MPs containing high concentrations of IL-1beta that cause diffuse
      inflammatory vascular injury.NEW & NOTEWORTHY Elevated levels of CO2 are often
      found in indoor air and cause adverse health effects, but the mechanisms have not
      been identified. In a murine model, environmentally relevant levels of CO2 were
      found to cause diffuse vascular damage because neutrophils are stimulated to
      produce microparticles that contain high concentrations of interleukin-1beta.

PMID- 28495850
TI  - A young man with elbow pain.

PMID- 28495848
TI  - Physical activity modulates corticospinal excitability of the lower limb in young
      and old adults.
AB  - Aging is associated with reduced neuromuscular function, which may be due in part
      to altered corticospinal excitability. Regular physical activity (PA) may
      ameliorate these age-related declines, but the influence of PA on corticospinal
      excitability is unknown. The purpose of this study was to determine the influence
      of age, sex, and PA on corticospinal excitability by comparing the stimulus
      response curves of motor evoked potentials (MEP) in 28 young (22.4 +/- 2.2 yr; 14
      women and 14 men) and 50 old adults (70.2 +/- 6.1 yr; 22 women and 28 men) who
      varied in activity levels. Transcranial magnetic stimulation was used to elicit
      MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction)
      with 5% increments in stimulator intensity until the maximum MEP amplitude.
      Stimulus-response curves of MEP amplitudes were fit with a four-parameter
      sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was
      assessed with tri-axial accelerometry and participants categorized into either
      those meeting the recommended PA guidelines for optimal health benefits (>10,000
      steps/day, high-PA; n = 21) or those not meeting the guidelines (<10,000
      steps/day, low-PA; n = 41). The MEP amplitudes and slopemax were greater in the
      low-PA compared with the high-PA group (P < 0.05). Neither age nor sex influenced
      the stimulus-response curve parameters (P > 0.05), suggesting that habitual PA
      influenced the excitability of the corticospinal tract projecting to the lower
      limb similarly in both young and old adults. These findings provide evidence that
      achieving the recommended PA guidelines for optimal health may mediate its
      effects on the nervous system by decreasing corticospinal excitability.NEW &
      NOTEWORTHY Transcranial magnetic stimulation was used to determine whether
      achieving the recommended 10,000 steps/day for optimal health influenced the
      excitability of the corticospinal tract projecting to the knee extensor muscles.
      Irrespective of age and sex, individuals who achieved >10,000 steps/day had lower
      corticospinal excitability than those who performed <10,000 steps/day, possibly
      representing greater control of inhibitory and excitatory networks. Physical
      activity involving >10,000 steps/day may mediate its effects on the nervous
      system by decreasing corticospinal excitability.

PMID- 28495849
TI  - Neoadjuvant Trials in ER+ Breast Cancer: A Tool for Acceleration of Drug
      Development and Discovery.
AB  - Neoadjuvant therapy trials offer an excellent strategy for drug development and
      discovery in breast cancer, particularly in triple-negative and HER2
      overexpressing subtypes, where pathologic complete response is a good surrogate
      of long-term patient benefit. For estrogen receptor-positive (ER+) breast
      cancers, however, use of this strategy has been challenging because of the lack
      of validated surrogates of long-term efficacy and the overall good prognosis of
      the majority of patients with this cancer subtype. We review below the clinical
      benefits of neoadjuvant endocrine therapy for ER+/HER2-negative breast cancer,
      its use and limitations for drug development, prioritization of adjuvant and
      metastatic trials, and biomarker discovery.Significance: Neoadjuvant endocrine
      therapy is an excellent platform for the development of investigational drugs,
      triaging of novel combinations, biomarker validation, and discovery of mechanisms
      of drug resistance. This review summarizes the clinical and investigational
      benefits of this approach, with a focus on how to best integrate predictive
      biomarkers into novel clinical trial designs. Cancer Discov; 7(6); 561-74.
      (c)2017 AACR.

PMID- 28495851
TI  - Different macrophages equally induce EMT in endometria of adenomyosis and normal.
AB  - Endometrial cells and microenvironment are two important factors in the
      pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can
      induce eutopic epithelial cells of adenomyosis to suffer from epithelial
      mesenchymal transition (EMT). The aim of this study is to detect whether
      macrophages interacting with epithelial cells equally induce the EMT process in
      normal and eutopic endometria of healthy and adenomyotic patients; and whether
      macrophages parallelly polarize to M2. We investigated the expression levels of
      epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7
      (CK7), vimentin, transforming growth factor-beta1 (TGFB1), SMAD3 and pSMAD3 using
      immunohistochemistry and western blot, and then estimated the genetic levels of
      CD163, IL10 and MMP12 using real-time quantitative polymerase chain reaction (RT
      PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20
      patients with adenomyosis and 11 control patients without adenomyosis,
      respectively. The immunohistochemical analysis shows distinct EMT in eutopic
      endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3
      that indicate signal pathway of EMT were also higher in secretory phase.
      Macrophages can induce EMT process in primary endometrial epithelial cells
      derived from normal and eutopic endometria. After co-culturing, THP-1-derived
      macrophages polarized to M2. Compared with the eutopic endometrium group, further
      polarization to M2 was observed in the normal endometrium group. These results
      indicate that adenomyosis may be promoted by the pathologic EMT of epithelial
      cells, which is induced by macrophages that incapably polarize to M2.

PMID- 28495852
TI  - High-throughput mRNA sequencing of stromal cells from endometriomas and
      endometrium.
AB  - The aetiology of endometriosis is still unclear and to find mechanisms behind the
      disease development, it is important to study each cell type from endometrium and
      ectopic lesions independently. The objective of this study was to uncover
      complete mRNA profiles in uncultured stromal cells from paired samples of
      endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed
      over 1300 dysregulated genes in stromal cells from ectopic lesions, including
      several novel genes in the context of endometriosis. Functional annotation
      analysis of differentially expressed genes highlighted pathways related to cell
      adhesion, extracellular matrix-receptor interaction and complement and
      coagulation cascade. Most importantly, we found a simultaneous upregulation of
      complement system components and inhibitors, indicating major imbalances in
      complement regulation in ectopic stromal cells. We also performed in vitro
      experiments to evaluate the effect of endometriosis patients' peritoneal fluid
      (PF) on complement system gene expression levels, but no significant impact of PF
      on C3, CD55 and CFH levels was observed. In conclusion, the use of isolated
      stromal cells enables to determine gene expression levels without the background
      interference of other cell types. In the future, a new standard design studying
      all cell types from endometriotic lesions separately should be applied to reveal
      novel mechanisms behind endometriosis pathogenesis.

PMID- 28495853
TI  - Transgenerational transmission of asthma risk after exposure to environmental
      particles during pregnancy.
AB  - Exposure to environmental particles during pregnancy increases asthma
      susceptibility of the offspring. We tested the hypothesis that this transmission
      continues to F2 and F3 generations and occurs via epigenetic mechanisms. We
      compared allergic susceptibility of three generations of BALB/c offspring after a
      single maternal exposure during pregnancy to diesel exhaust particles or
      concentrated urban air particles. After pregnant dams received intranasal
      instillations of particle suspensions or control, their F1, F2, and F3 offspring
      were tested in a low-dose ovalbumin protocol for sensitivity to allergic asthma.
      We found that the elevated susceptibility after maternal exposure to particles
      during pregnancy persists into F2 and, with lesser magnitude, into F3
      generations. This was evident from elevated eosinophil counts in bronchoalveolar
      lavage (BAL) fluid, histopathological changes of allergic airway disease, and
      increased BAL levels of IL-5 and IL-13. We have previously shown that dendritic
      cells (DCs) can mediate transmission of risk upon adoptive transfer. Therefore,
      we used an enhanced reduced representation bisulfite sequencing protocol to
      quantify DNA methylation in DCs from each generation. Distinct methylation
      changes were identified in F1, F2, and F3 DCs. The subset of altered loci shared
      across the three generations were not linked to known allergy genes or pathways
      but included a number of genes linked to chromatin modification, suggesting
      potential interaction with other epigenetic mechanisms (e.g., histone
      modifications). The data indicate that pregnancy airway exposure to diesel
      exhaust particles (DEP) triggers a transgenerationally transmitted asthma
      susceptibility and suggests a mechanistic role for epigenetic alterations in DCs
      in this process.

PMID- 28495855
TI  - Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and
      emphysema in a predictive mouse model not via CB1 receptor activation.
AB  - Sporadic clinical reports suggested that marijuana smoking induces spontaneous
      pneumothorax, but no animal models were available to validate these observations
      and to study the underlying mechanisms. Therefore, we performed a systematic
      study in CD1 mice as a predictive animal model and assessed the
      pathophysiological alterations in response to 4-mo-long whole body marijuana
      smoke with integrative methodologies in comparison with tobacco smoke. Bronchial
      responsiveness was measured with unrestrained whole body plethysmography, cell
      profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase
      activity with spectrophotometry, inflammatory cytokines with ELISA, and
      histopathological alterations with light microscopy. Daily marijuana inhalation
      evoked severe bronchial hyperreactivity after a week. Characteristic
      perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil
      and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte
      accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed
      bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis,
      emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4
      mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated
      with these changes. Airway hyperresponsiveness and inflammation were not altered
      in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke
      induced hyperresponsiveness after 2 mo and significantly later caused
      inflammatory cell infiltration/activation with only mild emphysema. We provide
      the first systematic and comparative experimental evidence that marijuana causes
      severe airway hyperresponsiveness, inflammation, tissue destruction, and
      emphysema, which are not mediated by the CB1 receptor.

PMID- 28495854
TI  - Role of apoptosis and autophagy in tuberculosis.
AB  - Tuberculosis (TB) is one of the oldest known human diseases and is transmitted by
      the bacteria Mycobacterium tuberculosis (Mtb). TB has a rich history with
      evidence of TB infections dating back to 5,800 bc TB is unique in its ability to
      remain latent in an individual for decades, with the possibility of later
      reactivation, causing widespread systemic symptoms. Currently, it is estimated
      that more than one-third of the world's population (~2 billion people) are
      infected with Mtb. Prolonged periods of therapy and complexity of treatment
      regimens, especially in active infection, have led to poor compliance in patients
      being treated for TB. Therefore, it is vitally important to have a thorough
      knowledge of the pathophysiology of Mtb to understand the disease progression, as
      well as to develop novel diagnostic tests and treatments. Alveolar macrophages
      represent both the primary host cell and the first line of defense against the
      Mtb infection. Apoptosis and autophagy of macrophages play a vital role in the
      pathogenesis and also in the host defense against Mtb. This review will outline
      the role of these two cellular processes in defense against Mtb with particular
      emphasis on innate immunity and explore developing therapies aimed at altering
      host responses to the disease.

PMID- 28495856
TI  - Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune
      cell function.
AB  - Innate immune cells of the respiratory tract are the first line of defense
      against pathogenic and environmental insults. Failure of these cells to perform
      their immune functions leaves the host susceptible to infection and may
      contribute to impaired resolution of inflammation. While combustible tobacco
      cigarettes have been shown to suppress respiratory immune cell function, the
      effects of flavored electronic cigarette liquids (e-liquids) and individual
      flavoring agents on respiratory immune cell responses are unknown. We
      investigated the effects of seven flavored nicotine-free e-liquids on primary
      human alveolar macrophages, neutrophils, and natural killer (NK) cells. Cells
      were challenged with a range of e-liquid dilutions and assayed for their
      functional responses to pathogenic stimuli. End points included phagocytic
      capacity (neutrophils and macrophages), neutrophil extracellular trap formation,
      proinflammatory cytokine production, and cell-mediated cytotoxic response (NK
      cells). E-liquids were then analyzed via mass spectrometry to identify individual
      flavoring components. Three cinnamaldehyde-containing e-liquids exhibited dose
      dependent broadly immunosuppressive effects. Quantitative mass spectrometry was
      used to determine concentrations of cinnamaldehyde in each of the three e
      liquids, and cells were subsequently challenged with a range of cinnamaldehyde
      concentrations. Cinnamaldehyde alone recapitulated the impaired function observed
      with e-liquid exposures, and cinnamaldehyde-induced suppression of macrophage
      phagocytosis was reversed by addition of the small-molecule reducing agent 1,4
      dithiothreitol. We conclude that cinnamaldehyde has the potential to impair
      respiratory immune cell function, illustrating an immediate need for further
      toxicological evaluation of chemical flavoring agents to inform regulation
      governing their use in e-liquid formulations.

PMID- 28495857
TI  - TGF-beta1 induces Fstl1 via the Smad3-c-Jun pathway in lung fibroblasts.
AB  - Transforming growth factor (TGF)-beta1 has long been regarded as a central
      mediator of tissue fibrosis. Follistatin-like 1 (Fstl1) is a crucial profibrotic
      glycoprotein that is upregulated in fibrotic lung tissues, and it promotes
      fibrogenesis via facilitating TGF-beta signaling. Here we examined the signaling
      pathway by which TGF-beta1 upregulates Fstl1 expression in mouse pulmonary
      fibroblasts. TGF-beta1 regulated Fstl1 expression at both the transcriptional and
      translational levels. Although TGF-beta1 rapidly activated the Smad, MAPK, and
      Akt pathways in lung fibroblasts, only Smad2/3 inhibition eliminated TGF-beta1
      induced Fstl1 expression. Analysis of the luciferase reporter activity identified
      a functional c-Jun transcription site in the Fstl1 promoter. Our results
      suggested a critical role for the Smad3-c-Jun pathway in the regulation of Fstl1
      expression by TGF-beta1 during fibrogenesis.

PMID- 28495858
TI  - Comparative functional analysis of ribonuclease 1 homologs: molecular insights
      into evolving vertebrate physiology.
AB  - Pancreatic-type ribonucleases (ptRNases) comprise a class of highly conserved
      secretory endoribonucleases in vertebrates. The prototype of this enzyme family
      is ribonuclease 1 (RNase 1). Understanding the physiological roles of RNase 1 is
      becoming increasingly important, as engineered forms of the enzyme progress
      through clinical trials as chemotherapeutic agents for cancer. Here, we present
      an in-depth biochemical characterization of RNase 1 homologs from a broad range
      of mammals (human, bat, squirrel, horse, cat, mouse, and cow) and nonmammalian
      species (chicken, lizard, and frog). We discover that the human homolog of RNase
      1 has a pH optimum for catalysis, ability to degrade double-stranded RNA, and
      affinity for cell-surface glycans that are distinctly higher than those of its
      homologs. These attributes have relevance for human health. Moreover, the
      functional diversification of the 10 RNase 1 homologs illuminates the regulation
      of extracellular RNA and other aspects of vertebrate evolution.

PMID- 28495859
TI  - alpha-Synuclein may cross-bridge v-SNARE and acidic phospholipids to facilitate
      SNARE-dependent vesicle docking.
AB  - Misfolded alpha-synuclein (A-syn) is widely recognized as the primal cause of
      neurodegenerative diseases including Parkinson's disease and dementia with Lewy
      bodies. The normal cellular function of A-syn has, however, been elusive. There
      is evidence that A-syn plays multiple roles in the exocytotic pathway in the
      neuron, but the underlying molecular mechanisms are unclear. A-syn has been known
      to interact with negatively charged phospholipids and with vesicle SNARE protein
      VAMP2. Using single-vesicle docking/fusion assays, we find that A-syn promotes
      SNARE-dependent vesicles docking significantly at 2.5 uM. When phosphatidylserine
      (PS) is removed from t-SNARE-bearing vesicles, the docking enhancement by A-syn
      disappears and A-syn instead acts as an inhibitor for docking. In contrast,
      subtraction of PS from the v-SNARE-carrying vesicles enhances vesicle docking
      even further. Moreover, when we truncate the C-terminal 45 residues of A-syn that
      participates in interacting with VAMP2, the promotion of vesicle docking is
      abrogated. Thus, the results suggest that the A-syn's interaction with v-SNARE
      through its C-terminal tail and its concurrent interaction with PS in trans
      through its amphipathic N-terminal domain facilitate SNARE complex formation,
      whereby A-syn aids SNARE-dependent vesicle docking.

PMID- 28495860
TI  - P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization.
AB  - In the nervous system, extracellular ATP levels transiently increase in
      physiological and pathophysiological circumstances, effecting key signalling
      pathways in plasticity and inflammation through purinergic receptors. Pannexin 1
      (Panx1) forms ion- and metabolite-permeable channels that mediate ATP release and
      are particularly enriched in the nervous system. Our recent study demonstrated
      that elevation of extracellular ATP triggers Panx1 internalization in a
      concentration- and time-dependent manner. Notably, this effect was sensitive to
      inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs). Here, we report our
      novel findings from the detailed investigation of the mechanism underlying P2X7R
      Panx1 cross-talk in ATP-stimulated internalization. We demonstrate that
      extracellular ATP triggers and is required for the clustering of P2X7Rs and Panx1
      on Neuro2a cells through an extracellular physical interaction with the Panx1
      first extracellular loop (EL1). Importantly, disruption of P2X7R-Panx1 clustering
      by mutation of tryptophan 74 within the Panx1 EL1 inhibits Panx1 internalization.
      Notably, P2X7R-Panx1 clustering and internalization are independent of P2X7R
      associated intracellular signalling pathways (Ca2+ influx and Src activation).
      Further analysis revealed that cholesterol is required for ATP-stimulated P2X7R
      Panx1 clustering at the cell periphery. Taken together, our data suggest that
      extracellular ATP induces and is required for Panx1 EL1-mediated, cholesterol
      dependent P2X7R-Panx1 clustering and endocytosis. These findings have important
      implications for understanding the role of Panx1 in the nervous system and
      provide important new insights into Panx1-P2X7R cross-talk.

PMID- 28495861
TI  - Testosterone treatment and cardiovascular and venous thromboembolism risk: what
      is 'new'?
AB  - In men, testosterone (T) production declines as a function of ageing. Late-onset
      hypogonadism (LOH) is the most commonly used term to indicate this age-related
      condition. In LOH, the relative clinical significance and the potential benefit
      of testosterone treatment (TTh) are still the subject of strong criticisms in the
      scientific community. The debate is further complicated by the recent position
      statement of the US Food and Drug Administration (FDA) emphasizing that, in LOH,
      the benefits and safety of TTh have not been fully established. Hence, the FDA
      required a labeling change to inform patients about a possible increased
      cardiovascular (CV) risk of TTh. Similar considerations were previously released
      by the FDA and by Health Canada concerning a TTh-related venous thromboembolism
      (VTE) risk. In this review, we will summarize the available evidence concerning a
      possible link among TTh and CV and VTE risks. For this purpose, data derived from
      epidemiological studies analyzing relationships between the aforementioned risks
      and endogenous T levels will be analyzed. In addition, evidence deriving from
      interventional studies including pharmacoepidemiological and placebo-controlled
      randomized controlled trials (RCTs) will be examined. Our analysis shows that
      available data do not support an increased CV risk related to TTh. Similar
      considerations can be drawn for the relationship between TTh and VTE. The
      previously reported cases of TTh-related VTE were frequently related to a
      previously undiagnosed thrombophilia-hypofibrinolysis status. Hence, an
      anamnestic screening for thrombophilia before starting TTh is recommended, just
      as it is for the use of oral contraceptives.

PMID- 28495862
TI  - The Diagnosis-Wide Landscape of Hospital-Acquired AKI.
AB  - BACKGROUND AND OBJECTIVES: The exploration of electronic hospital records offers
      a unique opportunity to describe in-depth the prevalence of conditions associated
      with diagnoses at an unprecedented level of comprehensiveness. We used a
      diagnosis-wide approach, adapted from phenome-wide association studies (PheWAS),
      to perform an exhaustive analysis of all diagnoses associated with hospital
      acquired AKI (HA-AKI) in a French urban tertiary academic hospital over a period
      of 10 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively
      extracted all diagnoses from an i2b2 (Informatics for Integrating Biology and the
      Bedside) clinical data warehouse for patients who stayed in this hospital between
      2006 and 2015 and had at least two plasma creatinine measurements performed
      during the first week of their stay. We then analyzed the association between HA
      AKI and each International Classification of Diseases (ICD)-10 diagnostic
      category to draw a comprehensive picture of diagnoses associated with AKI.
      Hospital stays for 126,736 unique individuals were extracted. RESULTS:
      Hemodynamic impairment and surgical procedures are the main factors associated
      with HA-AKI and five clusters of diagnoses were identified: sepsis, heart
      diseases, polytrauma, liver disease, and cardiovascular surgery. The ICD-10 code
      corresponding to AKI (N17) was recorded in 30% of the cases with HA-AKI
      identified, and in this situation, 20% of the diagnoses associated with HA-AKI
      corresponded to kidney diseases such as tubulointerstitial nephritis, necrotizing
      vasculitis, or myeloma cast nephropathy. Codes associated with HA-AKI that
      demonstrated the greatest increase in prevalence with time were related to
      influenza, polytrauma, and surgery of neoplasms of the genitourinary system.
      CONCLUSIONS: Our approach, derived from PheWAS, is a valuable way to
      comprehensively identify and classify all of the diagnoses and clusters of
      diagnoses associated with HA-AKI. Our analysis delivers insights into how
      diagnoses associated with HA-AKI evolved over time. On the basis of ICD-10 codes,
      HA-AKI appears largely underestimated in this academic hospital.

PMID- 28495865
TI  - Ceramide counteracts the effects of ghrelin on the metabolic control of food
      intake in rainbow trout.
AB  - In mammals, ceramides are involved in the modulation of the orexigenic effects of
      ghrelin (GHRL). We previously demonstrated in rainbow trout that
      intracerebroventricular (ICV) treatment with ceramide (2.5 ug/100 g fish)
      resulted in an anorexigenic response, i.e. a response opposed to that described
      in mammals, where ceramide treatment is orexigenic. Therefore, we hypothesized
      that the putative interaction between GHRL and ceramide must be different in
      fish. Accordingly, in a first experiment, we observed that ceramide levels in the
      hypothalamus of rainbow trout did not change after ICV treatment with GHRL. In a
      second experiment, we assessed whether the effects of GHRL treatment on the
      regulation of food intake in rainbow trout changed in the presence of ceramide.
      Thus, we injected ICV GHRL and ceramide alone or in combination to evaluate in
      hypothalamus and hindbrain changes in parameters related to the metabolic control
      of food intake. The presence of ceramide generally counteracted the effects
      elicited by GHRL on fatty acid-sensing systems, the capacity of integrative
      sensors (AMPK, mTOR and SIRT-1), proteins involved in cellular signalling
      pathways (Akt and FoxO1) and neuropeptides involved in the regulation of food
      intake (AgRP, NPY, POMC and CART). The results are discussed in the context of
      regulation of food intake by metabolic and endocrine inputs.

PMID- 28495863
TI  - Soluble Urokinase Plasminogen Activator Receptor and Outcomes in Patients with
      Diabetes on Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Soluble urokinase plasminogen activator receptor is a
      novel biomarker strongly predictive of cardiovascular outcomes implicated in the
      pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor
      levels, however, correlate with declining kidney function. It is unclear whether
      soluble urokinase plasminogen activator receptor levels remain associated with
      outcomes in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      measured plasma soluble urokinase plasminogen activator receptor levels in 1175
      patients (mean age =66+/-8 years old, 54% men) with type 2 diabetes mellitus on
      hemodialysis participating in the German Diabetes and Dialysis Study followed for
      a median of 4 years for outcomes including all-cause death, cardiovascular
      events, and infection-related mortality. Survival analysis was performed using
      stepwise Cox proportional hazards models adjusted for potential confounders.
      Also, adjustments were made for inflammatory markers (C-reactive protein and
      leukocyte count) and the oxidative stress marker asymmetric dimethyl arginine to
      investigate potential mediators of the relationship between soluble urokinase
      plasminogen activator receptor and outcomes. RESULTS: Median soluble urokinase
      plasminogen activator receptor levels were 10,521 pg/ml (interquartile range,
      9105-12,543 pg/ml). When stratified by tertiles, patients with soluble urokinase
      plasminogen activator receptor >11,633 pg/ml (third tertile) had adjusted 1.6
      fold higher mortality (hazard ratio, 1.60; 95% confidence interval, 1.27 to 2.03)
      compared with those with low soluble urokinase plasminogen activator receptor
      <9599 pg/ml (first tertile). Risks of sudden death and stroke were higher
      (adjusted hazard ratio, 1.98; 95% confidence interval, 1.27 to 3.09 and adjusted
      hazard ratio, 1.74; 95% confidence interval, 1.05 to 2.90, respectively),
      together accounting for higher incidence of cardiovascular events (adjusted
      hazard ratio, 1.48; 95% confidence interval, 1.15 to 1.89). Associations with
      outcomes persisted after adjusting for C-reactive protein, leukocyte count, and
      asymmetric dimethyl arginine. Addition of soluble urokinase plasminogen activator
      receptor to a risk factor model modestly improved risk discrimination for all
      cause death (DeltaC statistic, 0.02; 95% confidence interval, 0.00 to 0.03) and
      cardiovascular events (DeltaC statistic, 0.02; 95% confidence interval, 0.00 to
      0.05). CONCLUSIONS: The association of soluble urokinase plasminogen activator
      receptor levels with outcomes persists in patients on hemodialysis. Additional
      study is warranted to characterize the underlying pathways of that association,
      which may yield opportunities to develop new therapeutic strategies.

PMID- 28495866
TI  - Sources of variance in immunological traits: evidence of congruent latitudinal
      trends across species.
AB  - Among-population differences in immunological traits allow assessment of both
      evolutionary and plastic changes in organisms' resistance to pathogens. Such
      knowledge also provides information necessary to predict responses of such traits
      to environmental changes. Studies on latitudinal trends in insect immunity have
      so far yielded contradictory results, suggesting that multispecies approaches
      with highly standardised experimental conditions are needed. Here, we studied
      among-population differences of two parameters reflecting constitutive immunity
      phenoloxidase (PO) and lytic activity, using common-garden design on three
      distantly related moth species represented by populations ranging from northern
      Finland to Georgia (Caucasus). The larvae were reared at different temperatures
      and on different host plants under a crossed factors experimental design.
      Haemolymph samples for measurement of immune status were taken from the larvae
      strictly synchronously. Clear among-population differences could be shown only
      for PO activity in one species (elevated activity in the northern populations).
      There was some indication that the cases of total absence of lytic activity were
      more common in southern populations. The effects of temperature, host and sex on
      the immunological traits studied remained highly species specific. Some evidence
      was found that lytic activity may be involved in mediating trade-offs between
      immunity and larval growth performance. In contrast, PO activity rarely covaried
      with fitness-related traits, and neither were the values of PO and lytic activity
      correlated with each other. The relatively inconsistent nature of the detected
      patterns suggests that studies on geographic differences in immunological traits
      should involve multiple species, and rely on several immunological indices if
      general trends are a point of interest.

PMID- 28495867
TI  - Sex differences in the utilization of essential and non-essential amino acids in
      Lepidoptera.
AB  - The different reproductive strategies of males and females underlie differences
      in behavior that may also lead to differences in nutrient use between the two
      sexes. We studied sex differences in the utilization of two essential amino acids
      (EAAs) and one non-essential amino acid (NEAA) by the Carolina sphinx moth
      (Manduca sexta). On day one post-eclosion from the pupae, adult male moths
      oxidized greater amounts of larva-derived AAs than females, and more nectar
      derived AAs after feeding. After 4 days of starvation, the opposite pattern was
      observed: adult females oxidized more larva-derived AAs than males. Adult males
      allocated comparatively small amounts of nectar-derived AAs to their first
      spermatophore, but this allocation increased substantially in the second and
      third spermatophores. Males allocated significantly more adult-derived AAs to
      their flight muscle than females. These outcomes indicate that adult male and
      female moths employ different strategies for allocation and oxidation of dietary
      AAs.

PMID- 28495868
TI  - Transforming growth factor beta-1 (TGF-beta1) stimulates collagen synthesis in
      cultured rainbow trout cardiac fibroblasts.
AB  - Cold acclimation of rainbow trout, Oncorhynchus mykiss, causes collagen to
      increase within the extracellular matrix (ECM) of the myocardium, while warm
      acclimation has the opposite effect. The mechanism responsible for this
      remodelling response is not known. In mammals, transforming growth factor beta-1
      (TGF-beta1) stimulates collagen deposition within the myocardial ECM. Therefore,
      we hypothesized that TGF-beta1 regulates trout myocardial ECM turnover and
      predicted that TGF-beta1 would induce collagen deposition in cultured rainbow
      trout cardiac fibroblasts. We found that treatment of trout cardiac fibroblasts
      with 15 ng ml-1 human recombinant TGF-beta1 caused an increase in total collagen
      at 48 and 72 h and an increase in collagen type I protein after 7 days. We also
      found that TGF-beta1 treatment caused an increase in the transcript abundance of
      tissue inhibitor of metalloproteinase 2 (timp-2) and matrix metalloproteinase 9
      (mmp-9) at 24 h. Cells treated with TGF-beta1 also had lower levels of the gene
      transcript for mmp-2 after 48 h and higher levels of the gene transcript for
      collagen type I alpha1 (col1a1) after 72 h. These changes in gene expression
      suggest that the increase in collagen deposition is due to a decrease in the
      activity of matrix metalloproteinases and an increase in collagen synthesis.
      Together, these results indicate that TGF-beta1 is a regulator of ECM composition
      in cultured trout cardiac fibroblasts and suggest that this cytokine may play a
      role in regulating collagen content in the trout heart during thermal
      acclimation.

PMID- 28495869
TI  - Kinematics of ram filter feeding and beat-glide swimming in the northern anchovy
      Engraulis mordax.
AB  - In the dense aquatic environment, the most adept swimmers are streamlined to
      reduce drag and increase the efficiency of locomotion. However, because they open
      their mouth to wide gape angles to deploy their filtering apparatus, ram filter
      feeders apparently switch between diametrically opposite swimming modes: highly
      efficient, streamlined 'beat-glide' swimming, and ram filter feeding, which has
      been hypothesized to be a high-cost feeding mode because of presumed increased
      drag. Ram filter-feeding forage fish are thought to play an important role in the
      flux of nutrients and energy in upwelling ecosystems; however, the biomechanics
      and energetics of this feeding mechanism remain poorly understood. We quantified
      the kinematics of an iconic forage fish, the northern anchovy, Engraulis mordax,
      during ram filter feeding and non-feeding, mouth-closed beat-glide swimming.
      Although many kinematic parameters between the two swimming modes were similar,
      we found that swimming speeds and tailbeat frequencies were significantly lower
      during ram feeding. Rather than maintain speed with the school, a speed which
      closely matches theoretical optimum filter-feeding speeds was consistently
      observed. Beat-glide swimming was characterized by high variability in all
      kinematic parameters, but variance in kinematic parameters was much lower during
      ram filter feeding. Under this mode, body kinematics are substantially modified,
      and E. mordax swims more slowly and with decreased lateral movement along the
      entire body, but most noticeably in the anterior. Our results suggest that
      hydrodynamic effects that come with deployment of the filtering anatomy may limit
      behavioral options during foraging and result in slower swimming speeds during
      ram filtration.

PMID- 28495870
TI  - Early life experience drives short-term acclimation of metabolic and
      osmoregulatory traits in the leaf-eared mouse.
AB  - We studied the putative effect of early life experience on the physiological
      flexibility of metabolic and osmoregulatory traits in the leaf-eared mouse,
      Phyllotis darwini, an altricial rodent inhabiting seasonal Mediterranean
      environments. Adult individuals were collected in central Chile and maintained in
      breeding pairs. Pups were isolated after weaning and acclimated to different
      temperatures (cold or warm) and water availability (unrestricted and restricted)
      until adulthood. Subsequently, individuals were re-acclimated to the opposite
      treatment. Rodents reared in the warm and subjected to water restriction had
      lower basal metabolic rate (BMR), total evaporative water loss (TEWL) and body
      mass (Mb) compared with those developing in the cold treatment; nevertheless,
      individuals subjected to warm temperatures had greater relative medullary
      thickness (RMT) and urine concentrating ability (UCA). Cold-reared rodents re
      acclimated to warm conditions exhibited physiological flexibility of metabolic
      traits; however, their osmoregulatory attributes did not vary. Conversely, warm
      reared rodents re-acclimated to cold had reduced RMT and UCA, but the metabolic
      traits of these individuals did not change. These results suggest a trade-off
      between metabolic performance and renal capabilities that might hinder
      physiological acclimation. Our results support the hypothesis of ontogenetic
      dependence of short-term acclimation in osmoregulatory and metabolic traits in P.
      darwini.

PMID- 28495871
TI  - Embryonic hypoxia programmes postprandial cardiovascular function in adult common
      snapping turtles (Chelydra serpentina).
AB  - Reduced oxygen availability (hypoxia) is a potent stressor during embryonic
      development, altering the trajectory of trait maturation and organismal
      phenotype. We previously documented that chronic embryonic hypoxia has a lasting
      impact on the metabolic response to feeding in juvenile snapping turtles
      (Chelydra serpentina). Turtles exposed to hypoxia as embryos [10% O2 (H10)]
      exhibited an earlier and increased peak postprandial oxygen consumption rate,
      compared with control turtles [21% O2 (N21)]. In the current study, we measured
      central blood flow patterns to determine whether the elevated postprandial
      metabolic response in H10 turtles is linked to lasting impacts on convective
      transport. Five years after hatching, turtles were instrumented to quantify
      systemic ([Formula: see text]) and pulmonary ([Formula: see text]) blood flows
      and heart rate (fH) before and after a ~5% body mass meal. In adult N21 and H10
      turtles, fH was increased significantly by feeding. Although total stroke volume
      (VS,tot) remained at fasted values, this tachycardia contributed to an elevation
      in total cardiac output ([Formula: see text]). However, there was a postprandial
      reduction in a net left-right (L-R) shunt in N21 snapping turtles only. Relative
      to N21 turtles, H10 animals exhibited higher [Formula: see text] due to increased
      blood flow through the right systemic outflow vessels of the heart. This effect
      of hypoxic embryonic development, reducing a net L-R cardiac shunt, may support
      the increased postprandial metabolic rate we previously reported in H10 turtles,
      and is further demonstration of adult reptile cardiovascular physiology being
      programmed by embryonic hypoxia.

PMID- 28495872
TI  - The planarian TRPA1 homolog mediates extraocular behavioral responses to near
      ultraviolet light.
AB  - Although light is most commonly thought of as a visual cue, many animals possess
      mechanisms to detect light outside of the eye for various functions, including
      predator avoidance, circadian rhythms, phototaxis and migration. Here we confirm
      that planarians (like Caenorhabditis elegans, leeches and Drosophila larvae) are
      capable of detecting and responding to light using extraocular photoreception. We
      found that, when either eyeless or decapitated worms were exposed to near
      ultraviolet (near-UV) light, intense wild-type photophobic behaviors were still
      observed. Our data also revealed that behavioral responses to green wavelengths
      were mediated by ocular mechanisms, whereas near-UV responses were driven by
      extraocular mechanisms. As part of a candidate screen to uncover the genetic
      basis of extraocular photoreception in the planarian species Schmidtea
      mediterranea, we identified a potential role for a homolog of the transient
      receptor potential channel A1 (TRPA1) in mediating behavioral responses to
      extraocular light cues. RNA interference (RNAi) to Smed-TrpA resulted in worms
      that lacked extraocular photophobic responses to near-UV light, a mechanism
      previously only identified in Drosophila These data show that the planarian TRPA1
      homolog is required for planarian extraocular-light avoidance and may represent a
      potential ancestral function of this gene. TRPA1 is an evolutionarily conserved
      detector of temperature and chemical irritants, including reactive oxygen species
      that are byproducts of UV-light exposure. Our results suggest that planarians
      possess extraocular photoreception and display an unconventional TRPA1-mediated
      photophobic response to near-UV light.

PMID- 28495873
TI  - Intestinal digestive enzyme modulation in house sparrow nestlings occurs within
      24 h of a change in diet composition.
AB  - Nestling house sparrows near fledging age (12 days) were previously found to
      reversibly modulate the activity of their intestinal digestive enzymes in
      response to changes in diet composition. However, it is not known how quickly
      nestlings can adjust to new diets with different substrate compositions, nor is
      it known how early in life nestlings can modulate their enzyme activity in
      response to changes in diet. In the present study, 3-day-old nestlings were
      captured from the wild and fed and switched among contrasting diets - one high in
      protein and low in carbohydrate and another higher in carbohydrate and with
      lower, but adequate, protein - in order to determine (1) how quickly house
      sparrow nestlings could adjust to changes in diet composition, (2) how early in
      life nestlings could modulate their digestive enzyme activity in response to
      these changes and (3) which digestive enzymes could be modulated in house sparrow
      nestlings earlier in life. We found that house sparrow nestlings as young as 3
      days post-hatch were capable of modulating their intestinal disaccharidase
      activity within 24 h of a change in diet composition, and nestlings gained the
      ability to modulate aminopeptidase-N by 6 or 7 days of age. To our knowledge,
      this is the first evidence of digestive enzyme modulation completed within 24 h
      of a change in diet in an avian species and the first study to show intestinal
      digestive enzyme modulation in response to changes in diet composition in any
      animal this early in development.

PMID- 28495874
TI  - Cranking up the heat: relationships between energetically costly song features
      and the increase in thorax temperature in male crickets and katydids.
AB  - Sexual displays of acoustically signalling insects are used in the context of
      mate attraction and mate choice. While energetic investment in sound production
      can increase the reproductive success of the sender, this entails metabolic
      costs. Resource allocation to sexually selected, reproductive traits can trade
      off against allocation to naturally selected traits (e.g. growth, immunity) when
      individuals' energy budgets are limited. Estimating the magnitude of the costs
      invested in acoustic signalling is necessary to understand this trade-off and its
      influence on fitness and life history. To compare the costs associated with
      acoustic signalling for two ensiferan species, we simultaneously took respiratory
      measurements to record the rate of CO2 production and used infrared thermography
      to measure the increase in thorax temperature. Furthermore, to identify what
      combinations of acoustic parameters were energetically costly for the sender, we
      recorded the calling songs of 22 different cricket and katydid species for a
      comparative analysis and measured their thorax temperature while they sang.
      Acoustic signalling was energetically costly for Mecopoda sp. and Anurogryllus
      muticus, requiring a 12- and 16-fold increase over resting levels in the CO2
      production rate. Moreover, calling increased thorax temperature, on average by
      7.6 and 5.8 degrees C, respectively. We found that the song intensity and
      effective calling rate, not simply the chirp/trill duty cycle or the pulse rate
      alone, were good predictors for the thorax temperature increase in males.

PMID- 28495875
TI  - Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with
      apoptotic cells.
AB  - Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL
      13-dependent host responses during helminth infection. Here we show that IL-4 or
      IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells
      induced the tissue repair program in macrophages. Genetic ablation of sensors of
      apoptotic cells impaired the proliferation of tissue-resident macrophages and the
      induction of anti-inflammatory and tissue repair genes in the lungs after
      helminth infection or in the gut after induction of colitis. By contrast, the
      recognition of apoptotic cells was dispensable for cytokine-dependent induction
      of pattern recognition receptor, cell adhesion, or chemotaxis genes in
      macrophages. Detection of apoptotic cells can therefore spatially
      compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble
      cytokines such as IL-4 or IL-13.

PMID- 28495876
TI  - A subcellular map of the human proteome.
AB  - Resolving the spatial distribution of the human proteome at a subcellular level
      can greatly increase our understanding of human biology and disease. Here we
      present a comprehensive image-based map of subcellular protein distribution, the
      Cell Atlas, built by integrating transcriptomics and antibody-based
      immunofluorescence microscopy with validation by mass spectrometry. Mapping the
      in situ localization of 12,003 human proteins at a single-cell level to 30
      subcellular structures enabled the definition of the proteomes of 13 major
      organelles. Exploration of the proteomes revealed single-cell variations in
      abundance or spatial distribution and localization of about half of the proteins
      to multiple compartments. This subcellular map can be used to refine existing
      protein-protein interaction networks and provides an important resource to
      deconvolute the highly complex architecture of the human cell.

PMID- 28495877
TI  - A maternal-effect selfish genetic element in Caenorhabditis elegans.
AB  - Selfish genetic elements spread in natural populations and have an important role
      in genome evolution. We discovered a selfish element causing embryonic lethality
      in crosses between wild strains of the nematode Caenorhabditis elegans The
      element is made up of sup-35, a maternal-effect toxin that kills developing
      embryos, and pha-1, its zygotically expressed antidote. pha-1 has long been
      considered essential for pharynx development on the basis of its mutant
      phenotype, but this phenotype arises from a loss of suppression of sup-35
      toxicity. Inactive copies of the sup-35/pha-1 element show high sequence
      divergence from active copies, and phylogenetic reconstruction suggests that they
      represent ancestral stages in the evolution of the element. Our results suggest
      that other essential genes identified by genetic screens may turn out to be
      components of selfish elements.

PMID- 28495879
TI  - Dual-comb spectroscopy of water vapor with a free-running semiconductor disk
      laser.
AB  - Dual-comb spectroscopy offers the potential for high accuracy combined with fast
      data acquisition. Applications are often limited, however, by the complexity of
      optical comb systems. Here we present dual-comb spectroscopy of water vapor using
      a substantially simplified single-laser system. Very good spectroscopy
      measurements with fast sampling rates are achieved with a free-running dual-comb
      mode-locked semiconductor disk laser. The absolute stability of the optical comb
      modes is characterized both for free-running operation and with simple microwave
      stabilization. This approach drastically reduces the complexity for dual-comb
      spectroscopy. Band-gap engineering to tune the center wavelength from the
      ultraviolet to the mid-infrared could optimize frequency combs for specific gas
      targets, further enabling dual-comb spectroscopy for a wider range of industrial
      applications.

PMID- 28495880
TI  - SOX4 Allows Facultative beta-Cell Proliferation Through Repression of Cdkn1a.
AB  - The high-mobility group box transcription factor SOX4 is the most highly
      expressed SOX family protein in pancreatic islets, and mutations in Sox4 are
      associated with an increased risk of developing type 2 diabetes. We used an
      inducible beta-cell knockout mouse model to test the hypothesis that Sox4 is
      essential for the maintenance of beta-cell number during the development of type
      2 diabetes. Knockout of Sox4 at 6 weeks of age resulted in time-dependent
      worsening of glucose tolerance, impairment of insulin secretion, and diabetes by
      30 weeks of age. Immunostaining revealed a decrease in beta-cell mass in knockout
      mice that was caused by a 39% reduction in beta-cell proliferation. Gene
      expression studies revealed that induction of the cell cycle inhibitor Cdkn1a was
      responsible for the decreased proliferation in the knockout animals. Altogether,
      this study demonstrates that SOX4 is necessary for adult beta-cell replication
      through direct regulation of the beta-cell cycle.

PMID- 28495878
TI  - Local amplifiers of IL-4Ralpha-mediated macrophage activation promote repair in
      lung and liver.
AB  - The type 2 immune response controls helminth infection and maintains tissue
      homeostasis but can lead to allergy and fibrosis if not adequately regulated. We
      have discovered local tissue-specific amplifiers of type 2-mediated macrophage
      activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL
      4)-dependent macrophage proliferation and activation, accelerating parasite
      clearance and reducing pulmonary injury after infection with a lung-migrating
      helminth. In the peritoneal cavity and liver, C1q enhancement of type 2
      macrophage activation was required for liver repair after bacterial infection,
      but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of
      these structurally related defense collagens, SP-A and C1q, and the expression of
      their receptor, myosin 18A. These findings reveal the existence within different
      tissues of an amplification system needed for local type 2 responses.

PMID- 28495881
TI  - Dynamic expression and regulatory mechanism of TGF-beta signaling in chicken
      embryonic stem cells differentiating into spermatogonial stem cells.
AB  - The present study investigated the dynamic expression and regulatory mechanism of
      transforming growth factor beta (TGF-beta) signaling involved in embryonic stem
      cells (ESCs) differentiation into male germ cells. Candidate genes involved in
      TGF-beta signaling pathway were screened from RNA-sequencing (RNA-seq), which
      were further validated by quantitative real-time PCR (qRT-PCR). Bone
      morphogenetic protein 4 (BMP4) was used to induce differentiation of ESCs in
      vitro Inhibition of TGF-beta signaling pathway was reflected by Western blot of
      SMAD2 and SMAD5 expression. Differentiating efficiency of germ cells was
      evaluated by immunofluorescence and fluorescence-activated cell sorting (FACS).
      Germ cell marker genes were assessed by qRT-PCR in the differentiation process,
      with activation or inhibition of TGF-beta signaling pathway. In the process of in
      vitro induction, SMAD2 and SMAD5 were found to significantly up-regulated in BMP4
      group versus the control and inhibition groups after 4 and 14 days. Expression of
      CKIT, CVH, DAZL, STRA8, and INTEGRIN alpha6 were significantly increased in the
      BMP4 group compared with the control group, while down-regulated in the
      inhibition groups. The proportion of germ cell-like cells was decreased from
      17.9% to 2.2% after 4 days induction, and further decreased from 14.1% to 2.1%
      after 14 days induction. Correspondingly, expression of marker genes in germ
      cells was significantly lower. In vivo inhibition of TGF-beta signaling pathway
      reduced germ cells formation from 5.5% to 1.6%, and down-regulated the expression
      of CKIT, CVH, DAZL, STRA8, and INTEGRIN alpha6 In conclusion, our study reveals
      the mechanism regulating spermatogonial stem cells (SSCs) and lays the basis for
      further understanding of the regulatory network.

PMID- 28495883
TI  - A systems biology analysis connects insulin receptor signaling with glucose
      transporter translocation in rat adipocytes.
AB  - Type 2 diabetes is characterized by insulin resistance, which arises from
      malfunctions in the intracellular insulin signaling network. Knowledge of the
      insulin signaling network is fragmented, and because of the complexity of this
      network, little consensus has emerged for the structure and importance of the
      different branches of the network. To help overcome this complexity, systems
      biology mathematical models have been generated for predicting both the
      activation of the insulin receptor (IR) and the redistribution of glucose
      transporter 4 (GLUT4) to the plasma membrane. Although the insulin signal
      transduction between IR and GLUT4 has been thoroughly studied with modeling and
      time-resolved data in human cells, comparable analyses in cells from commonly
      used model organisms such as rats and mice are lacking. Here, we combined
      existing data and models for rat adipocytes with new data collected for the
      signaling network between IR and GLUT4 to create a model also for their
      interconnections. To describe all data (>140 data points), the model needed three
      distinct pathways from IR to GLUT4: (i) via protein kinase B (PKB) and Akt
      substrate of 160 kDa (AS160), (ii) via an AS160-independent pathway from PKB, and
      (iii) via an additional pathway from IR, e.g. affecting the membrane
      constitution. The developed combined model could describe data not used for
      training the model and was used to generate predictions of the relative
      contributions of the pathways from IR to translocation of GLUT4. The combined
      model provides a systems-level understanding of insulin signaling in rat
      adipocytes, which, when combined with corresponding models for human adipocytes,
      may contribute to model-based drug development for diabetes.

PMID- 28495882
TI  - Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and
      cone death in cyclic nucleotide-gated channel deficiency.
AB  - Endoplasmic reticulum (ER) stress and mislocalization of improperly folded
      proteins have been shown to contribute to photoreceptor death in models of
      inherited retinal degenerative diseases. In particular, mice with cone cyclic
      nucleotide-gated (CNG) channel deficiency, a model for achromatopsia, display
      both early-onset ER stress and opsin mistrafficking. By 2 weeks of age, these
      mice show elevated signaling from all three arms of the ER-stress pathway, and by
      1 month, cone opsin is improperly distributed away from its normal outer segment
      location to other retinal layers. This work investigated the role of Ca2+-release
      channels in ER stress, protein mislocalization, and cone death in a mouse model
      of CNG-channel deficiency. We examined whether preservation of luminal Ca2+
      stores through pharmacological and genetic suppression of ER Ca2+ efflux protects
      cones by attenuating ER stress. We demonstrated that the inhibition of ER Ca2+
      efflux channels reduced all three arms of ER-stress signaling while improving
      opsin trafficking to cone outer segments and decreasing cone death by 20-35%.
      Cone-specific gene deletion of the inositol-1,4,5-trisphosphate receptor type I
      (IP3R1) also significantly increased cone density in the CNG-channel-deficient
      mice, suggesting that IP3R1 signaling contributes to Ca2+ homeostasis and cone
      survival. Consistent with the important contribution of organellar Ca2+ signaling
      in this achromatopsia mouse model, significant differences in dynamic
      intraorganellar Ca2+ levels were detected in CNG-channel-deficient cones. These
      results thus identify a novel molecular link between Ca2+ homeostasis and cone
      degeneration, thereby revealing novel therapeutic targets to preserve cones in
      inherited retinal degenerative diseases.

PMID- 28495884
TI  - The uniqueness of subunit alpha of mycobacterial F-ATP synthases: An evolutionary
      variant for niche adaptation.
AB  - The F1F0 -ATP (F-ATP) synthase is essential for growth of Mycobacterium
      tuberculosis, the causative agent of tuberculosis (TB). In addition to their
      synthase function most F-ATP synthases possess an ATP-hydrolase activity, which
      is coupled to proton-pumping activity. However, the mycobacterial enzyme lacks
      this reverse activity, but the reason for this deficiency is unclear. Here, we
      report that a Mycobacterium-specific, 36-amino acid long C-terminal domain in the
      nucleotide-binding subunit alpha (Mtalpha) of F-ATP synthase suppresses its
      ATPase activity and determined the mechanism of suppression. First, we employed
      vesicles to show that in intact membrane-embedded mycobacterial F-ATP synthases
      deletion of the C-terminal domain enabled ATPase and proton-pumping activity. We
      then generated a heterologous F-ATP synthase model system, which demonstrated
      that transfer of the mycobacterial C-terminal domain to a standard F-ATP synthase
      alpha subunit suppresses ATPase activity. Single-molecule rotation assays
      indicated that the introduction of this Mycobacterium-specific domain decreased
      the angular velocity of the power-stroke after ATP binding. Solution X-ray
      scattering data and NMR results revealed the solution shape of Mtalpha and the 3D
      structure of the subunit alpha C-terminal peptide 521PDEHVEALDEDKLAKEAVKV540 of
      M. tubercolosis (Mtalpha(521-540)), respectively. Together with cross-linking
      studies, the solution structural data lead to a model, in which Mtalpha(521-540)
      comes in close proximity with subunit gamma residues 104-109, whose interaction
      may influence the rotation of the camshaft-like subunit gamma. Finally, we
      propose that the unique segment Mtalpha(514-549), which is accessible at the C
      terminus of mycobacterial subunit alpha, is a promising drug epitope.

PMID- 28495885
TI  - Proteolytic cleavage of the hydrophobic domain in the CaValpha2delta1 subunit
      improves assembly and activity of cardiac CaV1.2 channels.
AB  - Voltage-gated L-type CaV1.2 channels in cardiomyocytes exist as heteromeric
      complexes with the pore-forming CaValpha1, CaVbeta, and CaValpha2delta1 subunits.
      The full complement of subunits is required to reconstitute the native-like
      properties of L-type Ca2+ currents, but the molecular determinants responsible
      for the formation of the heteromeric complex are still being studied. Enzymatic
      treatment with phosphatidylinositol-specific phospholipase C, a phospholipase C
      specific for the cleavage of glycosylphosphatidylinositol (GPI)-anchored
      proteins, disrupted plasma membrane localization of the cardiac CaValpha2delta1
      prompting us to investigate deletions of its hydrophobic transmembrane domain.
      Patch-clamp experiments indicated that the C-terminally cleaved CaValpha2delta1
      proteins up-regulate CaV1.2 channels. In contrast, deleting the residues before
      the single hydrophobic segment (CaValpha2delta1 Delta1059-1063) impaired current
      up-regulation. CaValpha2delta1 mutants G1060I and G1061I nearly eliminated the
      cell-surface fluorescence of CaValpha2delta1, indicated by two-color flow
      cytometry assays and confocal imaging, and prevented CaValpha2delta1-mediated
      increase in peak current density and modulation of the voltage-dependent gating
      of CaV1.2. These impacts were specific to substitutions with isoleucine residues
      because functional modulation was partially preserved in CaValpha2delta1 G1060A
      and G1061A proteins. Moreover, C-terminal fragments exhibited significantly
      altered mobility in denatured immunoblots of CaValpha2delta1 G1060I and
      CaValpha2delta1 G1061I, suggesting that these mutant proteins were impaired in
      proteolytic processing. Finally, CaValpha2delta1 Delta1059-1063, but not
      CaValpha2delta1 G1060A, failed to co-immunoprecipitate with CaV1.2. Altogether,
      our data support a model in which small neutral hydrophobic residues facilitate
      the post-translational cleavage of the CaValpha2delta1 subunit at the predicted
      membrane interface and further suggest that preventing GPI anchoring of
      CaValpha2delta1 averts its cell-surface expression, its interaction with
      CaValpha1, and modulation of CaV1.2 currents.

PMID- 28495887
TI  - A man with chest tightness and burning limbs.

PMID- 28495886
TI  - The sigma-1 receptor modulates dopamine transporter conformation and cocaine
      binding and may thereby potentiate cocaine self-administration in rats.
AB  - The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by
      recapturing DA into the presynaptic terminals and is a principal target of the
      psychostimulant cocaine. The sigma-1 receptor (sigma1R) is a molecular chaperone,
      and its ligands have been shown to modulate DA neuronal signaling, although their
      effects on DAT activity are unclear. Here, we report that the prototypical
      sigma1R agonist (+)-pentazocine potentiated the dose response of cocaine self
      administration in rats, consistent with the effects of the sigmaR agonists PRE
      084 and DTG (1,3-di-o-tolylguanidine) reported previously. These behavioral
      effects appeared to be correlated with functional changes of DAT. Preincubation
      with (+)-pentazocine or PRE-084 increased the Bmax values of [3H]WIN35428 binding
      to DAT in rat striatal synaptosomes and transfected cells. A specific interaction
      between sigma1R and DAT was detected by co-immunoprecipitation and
      bioluminescence resonance energy transfer assays. Mutational analyses indicated
      that the transmembrane domain of sigma1R likely mediated this interaction.
      Furthermore, cysteine accessibility assays showed that sigma1R agonist
      preincubation potentiated cocaine-induced changes in DAT conformation, which were
      blocked by the specific sigma1R antagonist CM304. Moreover, sigma1R ligands had
      distinct effects on sigma1R multimerization. CM304 increased the proportion of
      multimeric sigma1Rs, whereas (+)-pentazocine increased monomeric sigma1Rs.
      Together these results support the hypothesis that sigma1R agonists promote
      dissociation of sigma1R multimers into monomers, which then interact with DAT to
      stabilize an outward-facing DAT conformation and enhance cocaine binding. We
      propose that this novel molecular mechanism underlies the behavioral potentiation
      of cocaine self-administration by sigma1R agonists in animal models.

PMID- 28495890
TI  - Paleoecology, Ploidy, Paleoatmospheric Composition, and Developmental Biology: A
      Review of the Multiple Uses of Fossil Stomata.

PMID- 28495891
TI  - Trimethylguanosine Synthase1 (TGS1) Is Essential for Chilling Tolerance.
AB  - Chilling stress is a major factor limiting plant development and crop
      productivity. Because the plant response to chilling is so complex, we are far
      from understanding the genes important in the response to chilling. To identify
      new genes important in chilling tolerance, we conducted a novel mutant screen,
      combining a confirmed SALK T-DNA insertion collection with traditional forward
      genetics. We screened a pool of more than 3700 confirmed homozygous SALK T-DNA
      insertion lines for visible defects under prolonged growth at 5 degrees C. Of the
      chilling-sensitive mutants we observed, mutations at one locus were characterized
      in detail. This gene, At1g45231, encodes an Arabidopsis (Arabidopsis thaliana)
      trimethylguanosine synthase (TGS1), previously uncharacterized in the plant
      kingdom. We confirmed that Arabidopsis TGS1 is a functional ortholog of other
      trimethylguanosine synthases based both on its in vitro methyltransferase
      activity and on its ability to rescue the cold-growth inhibition of a
      Saccharomyces cerevisiae tgs1Delta mutant in vivo. While tgs1 mutant plants grew
      normally at 22 degrees C, their vegetative and reproductive growth was severely
      compromised under chilling conditions. When we transgenically expressed TGS1 in
      the mutant plants, the chilling-sensitive phenotype was relieved, demonstrating
      that TGS1 is required for chilling tolerance.

PMID- 28495892
TI  - Bacterial Biosensors for in Vivo Spatiotemporal Mapping of Root Secretion.
AB  - Plants engineer the rhizosphere to their advantage by secreting various nutrients
      and secondary metabolites. Coupling transcriptomic and metabolomic analyses of
      the pea (Pisum sativum) rhizosphere, a suite of bioreporters has been developed
      in Rhizobium leguminosarum bv viciae strain 3841, and these detect metabolites
      secreted by roots in space and time. Fourteen bacterial lux fusion bioreporters,
      specific for sugars, polyols, amino acids, organic acids, or flavonoids, have
      been validated in vitro and in vivo. Using different bacterial mutants (nodC and
      nifH), the process of colonization and symbiosis has been analyzed, revealing
      compounds important in the different steps of the rhizobium-legume association.
      Dicarboxylates and sucrose are the main carbon sources within the nodules; in
      ineffective (nifH) nodules, particularly low levels of sucrose were observed,
      suggesting that plant sanctions affect carbon supply to nodules. In contrast,
      high myo-inositol levels were observed prior to nodule formation and also in nifH
      senescent nodules. Amino acid biosensors showed different patterns: a gamma
      aminobutyrate biosensor was active only inside nodules, whereas the phenylalanine
      bioreporter showed a high signal also in the rhizosphere. The bioreporters were
      further validated in vetch (Vicia hirsuta), producing similar results. In
      addition, vetch exhibited a local increase of nod gene-inducing flavonoids at
      sites where nodules developed subsequently. These bioreporters will be
      particularly helpful in understanding the dynamics of root exudation and the role
      of different molecules secreted into the rhizosphere.

PMID- 28495894
TI  - Morbidity and Mortality Associated With Balloon Aortic Valvuloplasty: A National
      Perspective.
AB  - BACKGROUND: The introduction of transcatheter aortic valve replacement (TAVR) led
      to renewed interest in balloon aortic valvuloplasty (BAV). We sought to assess
      contemporary trends in BAV utilization and their outcomes. METHODS AND RESULTS:
      The Nationwide Inpatient Sample was used to identify patients who underwent BAV
      between 2004 and 2013. In-hospital morbidity and mortality, and predictors of
      death after BAV were assessed. Outcomes of propensity-matched groups of patients
      undergoing elective BAV or TAVR were evaluated. BAV utilization increased from
      707 cases in 2004 to 3715 cases in 2013 (national estimates). Procedural and in
      hospital mortality were 1.4% and 8.5%, respectively. Vascular complications
      occurred in 7.0% of cases, blood transfusion in 17.5%, clinical stroke in 1.8%,
      and pacemaker implantation in 3.0%. The strongest predictors of in-hospital death
      were cardiogenic shock (odds ratio, 6.01; 95% confidence interval, 4.19-8.61;
      P<0.001), need for left ventricular assist device (odds ratio, 3.48; 95%
      confidence interval, 2.25-5.36; P<0.001), coagulopathy (odds ratio, 2.19; 95%
      confidence interval, 1.51-3.18; P<0.001), and low institutional volume of BAV
      (odds ratio, 1.58; 95% confidence interval, 1.06-2.37; P=0.03). In propensity
      matched patients undergoing elective BAV or TAVR, rates of in-hospital mortality
      (2.9% versus 3.5%; P=0.60), clinical stroke (1.6% versus 3.1%; P=0.10), and
      vascular complications (8.2% versus 10.9%; P=0.14) were similar. However, BAV was
      associated with lower rates of pacemaker implantation (2.9% versus 8.0%; P<0.001)
      and blood transfusion (12.8% versus 22.9%; P<0.001). CONCLUSIONS: In a
      contemporary national registry, BAV is associated with significant morbidity and
      mortality that are similar to TAVR. With the substantial increase in BAV
      utilization and the continuous improvement in TAVR outcomes, these data have
      important implications to aid clinicians in the selection of appropriate BAV
      candidates.

PMID- 28495893
TI  - Rice Sucrose Partitioning Mediated by a Putative Pectin Methyltransferase and
      Homogalacturonan Methylesterification.
AB  - Homogalacturonan (HG) is the main component of pectins. HG methylesterification
      has recently emerged as a key determinant controlling cell attachment, organ
      formation, and phyllotaxy. However, whether and how HG methylesterification
      affects intercellular metabolite transport has rarely been reported. Here, we
      identified and characterized knockout mutants of the rice (Oryza sativa) OsQUA2
      gene encoding a putative pectin methyltransferase. Osqua2 mutants exhibit a
      remarkable decrease in the degree of methylesterification of HG in the culm-sieve
      element cell wall and a markedly reduced grain yield. The culm of Osqua2 mutant
      plants contains excessive sucrose (Suc), and a 13CO2 feeding experiment showed
      that the Suc overaccumulation in the culm was caused by blocked Suc
      translocation. These and other findings demonstrate that OsQUA2 is essential for
      maintaining a high degree of methylesterification of HG in the rice culm-sieve
      element cell wall, which may be critical for efficient Suc partitioning and grain
      filling. In addition, our results suggest that the apoplastic pathway is involved
      in long-distance Suc transport in rice. The identification and characterization
      of the OsQUA2 gene and its functionality revealed a previously unknown
      contribution of HG methylesterification and provided insight into how
      modification of the cell wall regulates intercellular transport in plants.

PMID- 28495895
TI  - Management of Patients With Cardiac Arrest Complicating Myocardial Infarction in
      New York Before and After Public Reporting Policy Changes.
AB  - BACKGROUND: In 2010, New York State began excluding selected patients with
      cardiac arrest and coma from publicly reported mortality statistics after
      percutaneous coronary intervention. We evaluated the effects of this exclusion on
      rates of coronary angiography, revascularization, and mortality among patients
      with acute myocardial infarction and cardiac arrest. METHODS AND RESULTS: Using
      statewide hospitalization files, we identified discharges for acute myocardial
      infarction and cardiac arrest January 2003 to December 2013 in New York and
      several comparator states. A difference-in-differences approach was used to
      evaluate the likelihood of coronary angiography, revascularization, and in
      hospital mortality before and after 2010. A total of 26 379 patients with acute
      myocardial infarction and cardiac arrest (5619 in New York) were included. Of
      these, 17 141 (65%) underwent coronary angiography, 12 183 (46.2%) underwent
      percutaneous coronary intervention, and 2832 (10.7%) underwent coronary artery
      bypass grafting. Before 2010, patients with cardiac arrest in New York were less
      likely to undergo percutaneous coronary intervention compared with referent
      states (adjusted relative risk, 0.79; 95% confidence interval, 0.73-0.85;
      P<0.001). This relationship was unchanged after the policy change (adjusted
      relative risk, 0.82; 95% confidence interval, 0.76-0.89; interaction P=0.359).
      Adjusted risks of in-hospital mortality between New York and comparator states
      after 2010 were also similar (adjusted relative risk, 0.94; 95% confidence
      interval, 0.87-1.02; P=0.152 for post- versus pre-2010 in New York; adjusted
      relative risk, 0.88; 95% confidence interval, 0.84-0.92; P<0.001 for comparator
      states; interaction P=0.103). CONCLUSIONS: Exclusion of selected cardiac arrest
      cases from public reporting was not associated with changes in rates of
      percutaneous coronary intervention or in-hospital mortality in New York. Rates of
      revascularization in New York for cardiac arrest patients were lower throughout.

PMID- 28495896
TI  - Percutaneous Coronary Intervention of Saphenous Vein Graft.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) of saphenous vein grafts
      (SVGs) has historically been associated with a high risk of adverse ischemic
      events, but there is a paucity of contemporary data on the second-generation drug
      eluting stent use within SVG, and the relative importance of high platelet
      reactivity (HPR) in SVG PCI versus native lesion PCI is unknown. We studied
      ischemic and bleeding events after SVG PCI and their association with HPR.
      METHODS AND RESULTS: Subjects in the prospective, multicenter ADAPT-DES study
      (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) were
      stratified according to whether they had PCI of an SVG or a non-SVG lesion. Two
      year outcomes were compared between groups using univariate and multivariable Cox
      proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet
      reaction units >208 as measured by the VerifyNow assay; major adverse cardiac
      events were defined as the composite of cardiac death, myocardial infarction, or
      stent thrombosis. Among 8582 subjects in ADAPT-DES, 405 (4.7%) had SVG PCI. SVG
      PCI was independently associated with a higher 2-year risk of major adverse
      cardiac events (adjusted hazard ratio, 2.34; 95% confidence interval, 1.69-3.23;
      P<0.0001), ischemia-driven target vessel revascularization (adjusted hazard
      ratio, 1.82; 95% confidence interval, 1.37-2.42; P<0.0001), and stent thrombosis
      (adjusted hazard ratio, 2.26; 95% confidence interval, 1.42-3.59; P=0.0006), but
      not of bleeding (adjusted hazard ratio, 0.99; 95% confidence interval, 0.68-1.46;
      P=0.97). There was no statistical interaction between HPR and SVG PCI in regard
      to major adverse cardiac events (adjusted Pinteraction=0.99). CONCLUSIONS: SVG
      PCI is associated with a considerably higher risk of 2-year adverse ischemic
      events, with HPR conferring similar risk in SVG and non-SVG PCI. More potent and
      longer antiplatelet therapy may be beneficial for patients undergoing SVG PCI.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00638794.

PMID- 28495897
TI  - Geographical Difference of the Interaction of Sex With Treatment Strategy in
      Patients With Multivessel Disease and Left Main Disease: A Meta-Analysis From
      SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Bypass
      Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left
      Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting
      Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery
      Disease) Randomized Controlled Trials.
AB  - BACKGROUND: The impact of sex on clinical outcomes of percutaneous coronary
      intervention and coronary artery bypass graft for patients with multivessel
      coronary disease and unprotected left main disease could be dissimilar between
      Western and Asian populations. METHODS AND RESULTS: To assess clinical outcomes
      after percutaneous coronary intervention or coronary artery bypass graft in women
      and men with multivessel coronary disease and unprotected left main disease, a
      pooled analysis (n=3280) was performed using the patient-level data from 3 large
      randomized trials: SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery),
      PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in
      Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and
      Everolimus-Eluting Stent Implantation in the Treatment of Patients with
      Multivessel Coronary Artery Disease) trials. The primary end point was all-cause
      death. Of 3280 patients, 794 patients (24.2%) were women. The median follow-up
      period was 1806 days (1611-1837 days). In women, a high heterogeneity of the
      treatment effect among the 3 trials was found for all-cause death (I2>50%),
      whereas in men, it was consistent across the 3 trials. In the Western trial
      (SYNTAX), female sex favored coronary artery bypass graft compared with
      percutaneous coronary intervention (hazard ratio(percutaneous coronary
      intervention) 2.213; 95% confidence interval, 1.242-3.943; P=0.007), whereas in
      the Asian women (PRECOMBAT and BEST), the treatment effect was neutral between
      both strategies. Sex interaction with treatment strategy was evident in the
      Western trial (Pinteraction=0.019) but not in the Asian trials (PRECOMBAT
      Pinteraction=0.469 and BEST Pinteraction=0.472; I2=58%). CONCLUSIONS: The present
      meta-analysis suggested the presence of the heterogeneous sex-treatment
      interaction across Asian and Western trials. Considering the ongoing
      globalization of our medical practice, the heterogeneity of the sex-treatment
      interaction needs to be well recognized and taken into account during the
      decision making of the treatment strategy. CLINICAL TRIAL REGISTRATIONS: URL:
      https://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT00997828,
      NCT00422968.

PMID- 28495898
TI  - Balloon Aortic Valvuloplasty: Is It Still Relevant?

PMID- 28495899
TI  - Public Reporting: Small Changes Lead to Minimal Impact.

PMID- 28495900
TI  - Sex, Region, and Outcomes After Revascularization.

PMID- 28495901
TI  - Red meat: another inconvenient truth.

PMID- 28495902
TI  - Regio- and Stereo-Selective Oxidation of a Cardiovascular Drug, Metoprolol,
      Mediated by Cytochrome P450 2D and 3A Enzymes in Marmoset Livers.
AB  - A beta-blocker, metoprolol, is one of the in vivo probes for human cytochrome
      P450 (P450) 2D6. Investigation of nonhuman primate P450 enzymes helps to improve
      the accuracy of the extrapolation of pharmacokinetic data from animals into
      humans. Common marmosets (Callithrix jacchus) are a potential primate model for
      preclinical research, but the detailed roles of marmoset P450 enzymes in
      metoprolol oxidation remain unknown. In this study, regio- and stereo-selectivity
      of metoprolol oxidations by a variety of P450 enzymes in marmoset and human
      livers were investigated in vitro. Although liver microsomes from cynomolgus
      monkeys and rats preferentially mediated S-metoprolol O-demethylation and R
      metoprolol alpha-hydroxylation, respectively, those from humans, marmosets,
      minipigs, and dogs preferentially mediated R-metoprolol O-demethylation, in
      contrast to the slow rates of R- and S-metoprolol oxidation in mouse liver
      microsomes. R- and S-metoprolol O-demethylation activities in marmoset livers
      were strongly inhibited by quinidine and ketoconazole, and were significantly
      correlated with bufuralol 1'-hydroxylation and midazolam 1'-hydroxylation
      activities and also with P450 2D and 3A4 contents, which is different from the
      case in human livers that did not have any correlations with P450 3A-mediated
      midazolam 1'-hydroxylation. Recombinant human P450 2D6 enzyme and marmoset P450
      2D6/3A4 enzymes effectively catalyzed R-metoprolol O-demethylation, comparable to
      the activities of human and marmoset liver microsomes, respectively. These
      results indicated that the major roles of P450 2D enzymes for the regio- and
      stereo-selectivity of metoprolol oxidation were similar between human and
      marmoset livers, but the minor roles of P450 3A enzymes were unique to marmosets.

PMID- 28495903
TI  - Health Care Service and Outcomes Among an Estimated 6.7 Million Ambulatory Care
      Diabetic Foot Cases in the U.S.
AB  - OBJECTIVE: To evaluate ambulatory clinical cases of diabetic foot ulcers (DFUs)
      and diabetic foot infections (DFIs) in the U.S. from 2007 to 2013 and to assess
      outcomes of emergency department or inpatient (ED/IP) admission, number of clinic
      visits per year, and physician time spent per visit. RESEARCH DESIGN AND METHODS:
      A cross-sectional historical cohort analysis was conducted by using the
      nationally representative Centers for Disease Control and Prevention National
      Ambulatory Medical Care Survey data from 2007 to 2013, including patients age
      >=18 years with diabetes and either DFIs or DFUs. Study outcomes were analyzed by
      using generalized linear models controlling for key demographics and chronic
      conditions. RESULTS: Across the estimated 5.6 billion ambulatory care visits
      between 2007 and 2013, 784.8 million involved diabetes and ~6.7 million (0.8%)
      were for DFUs (0.3%) or DFIs (0.5%). Relative to other ambulatory clinical cases,
      multivariable analyses indicated that DFUs were associated with a 3.4 times
      higher odds of direct ED/IP admission (CI 1.01-11.28; P = 0.049), 2.1 times
      higher odds of referral to another physician (CI 1.14-3.71; P = 0.017), 1.9 times
      more visits in the past 12 months (CI 1.41-2.42; P < 0.001), and 1.4 times longer
      time spent per visit with the physician (CI 1.03-1.87; P = 0.033). DFIs were
      independently associated with a 6.7 times higher odds of direct ED referral or IP
      admission (CI 2.25-19.51; P < 0.001) and 1.5 times more visits in the past 12
      months (CI 1.14-1.90; P = 0.003). CONCLUSIONS: This investigation of an estimated
      6.7 million diabetic foot cases indicates markedly greater risks for both ED/IP
      admissions and number of outpatient visits, with DFUs also associated with a
      higher odds of referrals to other physicians and longer physician visit times.

PMID- 28495905
TI  - Long-term outcomes of the Boston type I keratoprosthesis in eyes with previous
      herpes simplex virus keratitis.
AB  - PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis
      (Kpro) in eyes with prior herpes simplex virus (HSV) keratitis. METHODS:
      Retrospective review of all Kpro procedures performed by a single surgeon from 1
      May 2004 to 1 January 2015. RESULTS: 13 of 173 Kpro procedures were performed in
      11 eyes with prior HSV keratitis. There was not a significant difference in the
      percentage of eyes with and without prior HSV keratitis with preoperative (9% vs
      8%, p=1.00) or postoperative (57% vs 60%, p=1.00) corrected distance visual
      acuity (CDVA) >=20/200 or in the percentage of contralateral eyes with
      preoperative CDVA >=20/50 (55% vs 30%, p=0.18). While several postoperative
      complications occurred approximately twice as often in eyes with prior HSV
      keratitis, including persistent epithelial defect (63.6% vs 34.1%; p=0.10),
      corneal infiltrate (27.3% vs 12.3%; p=0.17) and sterile vitritis (18.2% vs 9.4%;
      p=0.31), only cystoid macular oedema (45.5% vs 12.3%; p=0.01) was significantly
      more common. Similarly, while the Kpro retention failure rate in eyes with prior
      HSV keratitis was twice than that in eyes without it (0.15 vs 0.07 per year), the
      difference was not statistically significant (p=0.09). CONCLUSION: As greater
      than half of patients with unilateral HSV keratitis undergoing Kpro implantation
      have CDVA >=20/50 in the contralateral eye, and as the Kpro retention failure
      rate in eyes with prior HSV keratitis is twice than that in eyes without prior
      HSV keratitis, caution should be exercised when considering Kpro implantation in
      these patients.

PMID- 28495904
TI  - Assessing total retinal blood flow in diabetic retinopathy using multiplane en
      face Doppler optical coherence tomography.
AB  - AIM: To assess total retinal blood flow (TRBF) in diabetic retinopathy (DR) using
      multiplane en face Doppler optical coherence tomography (OCT). METHODS: A 70 kHz
      spectral-domain OCT system scanned a 2*2 mm area centred at the optic disc of the
      eyes with DR and healthy participants. The multiplane en face Doppler OCT
      algorithm generated a three-dimensional volumetric data set consisting of 195 en
      face planes. The TRBF was calculated from the maximum flow values of each
      branching retinal vein at an optimised en face plane. DR severity was graded
      according to the international clinical classification system. The generalised
      linear model method was used to compare flow values between DR groups and the
      control group. RESULTS: A total of 71 eyes from 71 participants were included.
      Ten eyes were excluded due to poor image quality. The within-visit repeatability
      of scans was 4.1% (coefficient of variation). There was no significant difference
      in the TRBF between the healthy (46.7+/-10.2 uL/min) and mild/moderate non
      proliferative DR (44.9+/-12.6 uL/min) groups. The TRBF in severe non
      proliferative DR (39.1+/-12.6 uL/min) and proliferative DR (28.9+/-8.85 uL/min)
      groups were significantly lower (p=0.04 and p<0.0001, respectively) than that of
      the healthy group. TRBF was correlated with DR disease severity (p<0.0001, linear
      trend test). CONCLUSION: The novel multiplane en face Doppler OCT method provided
      reliable measurements of TRBF in DR eyes. This may be a useful tool in
      understanding the pathophysiology of DR.

PMID- 28495906
TI  - Emergency corneal grafting in the UK: a 6-year analysis of the UK Transplant
      Registry.
AB  - BACKGROUND: Corneal graft (CG) surgery is the most common and successful tissue
      transplant worldwide. A small and important group of patients are operated in
      emergency situations, typically to save a perforated eye. Our knowledge of the
      indications and outcomes of emergency corneal graft (eCG) is limited. METHODS:
      Retrospective, multifactorial analysis of all CGs registered by the UK Transplant
      Service from April 1999 to March 2005. RESULTS: A total of 12 976 CGs were
      performed. 1330 (11.4%) were eCGs including 433 regrafts. Actual perforation
      occurred in 876 (65.9%) patients. 420 (31.5%) grafts were for tectonic purposes
      alone and 217 (16.3%) were also grafted for visual rehabilitation. The main
      diagnostic categories were infection (39.4%), non-infectious ulcerative keratitis
      (32.2%) and other causes (ectasias, previous ocular surgery, injury, dystrophies
      and opacification). Graft survival of first eCG at 1, 2 and 5 years was 78%, 66%
      and 47%, respectively. Best-corrected visual acuity of surviving grafts at 1 year
      was: 6/12 or better in 29.9%, 6/18 to 6/60 in 38.4%, counting finger to LP in
      30.6% and NPL in 1%, with worsening of vision in only 8.7% of the patients.
      CONCLUSION: This study which is the largest of its kind shows that despite the
      seriousness of the critical corneal pathology and the surgical challenges that it
      poses, the outcomes of eCG are favourable with most patients keeping their
      eyesight and avoiding immediate rejection. These clinical outcomes show the value
      of eye banking facilities that are developed to support corneal tissue supply for
      eCG.

PMID- 28495907
TI  - Interdevice comparison of retinal sensitivity assessments in a healthy
      population: the CenterVue MAIA and the Nidek MP-3 microperimeters.
AB  - BACKGROUND: To compare and correlate the retinal sensitivity measurements
      obtained with Nidek Microperimetry-3 (MP-3) and the CenterVue Macular Integrity
      Assessment (MAIA) microperimeters among healthy subjects. METHODS: In this
      prospective comparative study, 31 eyes of 23 subjects underwent complete
      ophthalmological examination including retinal sensitivity assessments using two
      microperimeters, the MP-3 (Nidek Technologies) and the MAIA (CenterVue). The mean
      retinal sensitivity (dB) and its corresponding luminance (asb) and contrast (log
      units) were analysed between the two instruments. The interdevice reproducibility
      and level of agreement between the sensitivity values of the devices were
      assessed. RESULTS: The mean retinal sensitivity (dB) measured by the MP-3
      (25.02+/-1.06 dB, range: 20.90-26.70) was significantly (p<0.0001) lower compared
      with the MAIA (30.68+/-0.74 dB, range: 28-31.84). The luminosity levels were
      significantly (p<0.0001) higher with the MP3 (7.75+/-1.31 asb, range: 6.44-9.06)
      compared with the MAIA (0.92+/-0.14 asb, range: 0.78-1.06). The contrast
      sensitivity was significantly higher for the MP-3 (0.94+/-0.33 log units, range:
      0.61-1.27) compared with the MAIA (0.23+/-0.03 log units, range: 0.20-0.26).
      Despite these absolute differences, the intraclass coefficient was 0.85 (95% CI
      0.70 to 0.92) between the two devices after applying a standard correction factor
      to each data point (MAIA sensitivity=MP-3 sensitivity+5.65) with a mean
      difference between MAIA and MP-3 of 0.01. CONCLUSION: Retinal sensitivity
      measures higher, but luminance and contrast sensitivity measure lower for MAIA
      generated values compared with the MP-3. The relationships, however, appeared
      fairly consistent, and application of a standard correction factor allowed the
      data to be inter-related, at least for normal eyes.

PMID- 28495908
TI  - Towards cultural materialism in the medical humanities: the case of blood
      rejuvenation.
AB  - This paper argues for an approach within the medical humanities that draws on the
      theoretical legacy of cultural materialism as a framework for reading cultural
      practices and their relationship to the social and economic order. It revisits
      the origins and development of cultural materialism in cultural studies and
      literary studies between the 1970s and 1990s and considers how, with adaptation,
      this methodology might facilitate ideological criticism focused on material
      formations of health, disease and the human body. I outline three key
      characteristics of a medicocultural materialist approach along these lines: (a)
      interdisciplinary work on a broad range of medical and cultural sources,
      including those drawn from 'popular' forms of culture; (b) the combination of
      historicist analysis with scrutiny of present-day contexts; (c) analyses that
      engage with political economy perspectives and/or the work of medical sociology
      in this area. The subsequent sections of the paper employ a medicocultural
      materialist approach to examine conjectural understandings of, and empirical
      investigations into, the capacity of transfused human blood to rejuvenate the
      ageing body. I trace textual faultlines that expose the structures of power which
      inform the movement of blood between bodies in 'medical gothic' fictions from the
      19th-century fin de siecle, including Mary Elizabeth Braddon's 'Good Lady
      Ducayne' (1896) and Bram Stoker's Dracula (1897). I conclude with a critique of
      biomedical innovations in blood rejuvenation in the era of medical neoliberalism,
      before considering the potential applications of medicocultural materialism to
      other topics within the field of the medical humanities.

PMID- 28495909
TI  - Pulse wave velocity is associated with cognitive impairment in hemodialysis
      patients.
AB  - Cognitive impairment in hemodialysis patients is common and associated with
      adverse outcomes. So far, the underlying pathogenesis remains unclear. Therefore,
      we examined the potential relationship between cognitive impairment and three
      different categories of risk factors with particular focus on arterial stiffness
      measured by pulse wave velocity (PWV). A total of 201 chronic hemodialysis
      patients underwent cognitive testing under standardized conditions using the
      Montreal Cognitive Assessment (MoCA). Demographic data including cardiovascular
      risk factors, dialysis-associated factors as well as factors related to chronic
      kidney disease (CKD) were analyzed. To account for arterial stiffness, PWV was
      measured by ambulatory blood pressure monitoried with an oscillometric device
      that records brachial blood pressure along with pulse waves. In our cohort, 60.2%
      of patients showed pathological MoCA test results indicating cognitive
      impairment. PWV was significantly associated with cognitive impairment apart from
      age, educational level, diabetes, and hypercholesterolemia. High prevalence of
      cognitive impairment in hemodialysis patients was confirmed. For the first time,
      an association between cognitive impairment and arterial stiffness was detected
      in a larger cohort of hemodialysis patients. Concerning the underlying
      pathogenesis of cognitive impairment, current results revealed a potential
      involvement of arterial stiffness, which has to be further evaluated in future
      studies.

PMID- 28495910
TI  - Oxidative imbalance and kidney damage in spontaneously hypertensive rats:
      activation of extrinsic apoptotic pathways.
AB  - In both humans and animals, essential hypertension acts as a risk factor for
      subclinical kidney damage and precedes renal dysfunction. Several lines of
      evidence indicate that hypertension and oxidative stress are closely related. The
      increase in vascular oxidative stress plays a key role in the pathophysiological
      consequences of hypertension, including kidney disease. Our study examined this
      issue in spontaneously hypertensive rat (SHR), a reliable model of essential
      hypertension. We used SHR 20 weeks old when hypertension is stably developed,
      vascular remodeling started, but kidney function is preserved. We examined
      plasmatic pro-oxidant and antioxidant status showing a significant alteration in
      oxidative balance in SHR. As index of oxidative damage, we evaluated lipid
      peroxidation in kidney, liver, and skeletal muscle, detecting a significant rise
      in lipid peroxidation levels in all SHR tissues, particularly relevant in kidney.
      In addition, we analyzed the expression of cytoplasmic antioxidant enzymes,
      superoxide dismutase 1 (SOD1) and glutatione S-tranferasi P1 (GSTP1). In SHR
      liver, SOD1 expression slight increased while we have not detected any variation
      in other tissues. Concerning GSTP1, SHR renal tissues did not display variations
      in enzyme expression, while in the other tissues, we observed a significant
      increase in both monomeric and pro-apoptotic dimeric form of the enzyme. By
      analyzing apoptotic signal, we founded c-Jun N-terminal kinase (JNK) activation
      in all SHR tissues, but only kidney presented extrinsic apoptotic pathway
      activation. Our results suggest that, in hypertensive animals with preserved
      renal function, despite the remarkable oxidative damage of renal tissues, only
      the extrinsic apoptotic pathway is activated.

PMID- 28495911
TI  - Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows
      Evidence of Immune Response and Viral Replication in Young Cancer Patients.
AB  - Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults
      via injection into the brain and superficial tumors. To determine the safety of
      administering HSV1716 to pediatric patients with cancer, we conducted a phase I
      trial of image-guided injection in young patients with relapsed or refractory
      extracranial cancers.Experimental Design: We delivered a single dose of 105 to
      107 infectious units of HSV1716 via computed tomography-guided intratumoral
      injection and measured tumor responses by imaging. Patients were eligible for up
      to three more doses if they achieved stable disease. We monitored HSV-1 serum
      titers and shedding by PCR and culture.Results: We administered a single dose of
      HSV1716 to eight patients and two doses to one patient. We did not observe any
      dose-limiting toxicities. Adverse events attributed to virus included low-grade
      fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at
      baseline showed seroconversion on day 28. Six of nine patients had detectable HSV
      1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo
      virus replication. Two patients had transient focal increases in metabolic
      activity on 18fluorine-deoxyglucose PET, consistent with inflammatory reactions.
      In one case, the same geographic region that flared later appeared necrotic on
      imaging. No patient had an objective response to HSV1716.Conclusions:
      Intratumoral HSV1716 is safe and well-tolerated without shedding in children and
      young adults with late-stage, aggressive cancer. Viremia consistent with virus
      replication and transient inflammatory reactions hold promise for future HSV1716
      studies. Clin Cancer Res; 23(14); 3566-74. (c)2017 AACR.

PMID- 28495912
TI  - Uncertainty in medicine.

PMID- 28495913
TI  - Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in
      myeloma relapsing after autologous transplantation.
AB  - To investigate cytogenetic evolution after upfront autologous stem cell
      transplantation for newly diagnosed myeloma we retrospectively analyzed
      fluorescence in situ hybridization results of 128 patients with paired bone
      marrow samples from the time of primary diagnosis and at relapse. High-risk
      cytogenetic abnormalities (deletion 17p and/or gain 1q21) occurred more
      frequently after relapse (odds ratio: 6.33; 95% confidence interval: 1.86-33.42;
      P<0.001). No significant changes were observed for defined IGH translocations
      [t(4;14); t(11;14); t(14;16)] or hyperdiploid karyotypes between primary
      diagnosis and relapse. IGH translocations with unknown partners occurred more
      frequently at relapse. New deletion 17p and/or gain 1q21 were associated with
      cytogenetic heterogeneity, since some de novo lesions with different copy numbers
      were present only in subclones. No distinct baseline characteristics were
      associated with the occurrence of new high-risk cytogenetic abnormalities after
      progression. Patients who relapsed after novel agent-based induction therapy had
      an increased risk of developing high-risk aberrations (odds ratio 10.82; 95%
      confidence interval: 1.65-127.66; P=0.03) compared to those who were treated with
      conventional chemotherapy. Survival analysis revealed dismal outcomes regardless
      of whether high-risk aberrations were present at baseline (hazard ratio, 3.53;
      95% confidence interval: 1.53-8.14; P=0.003) or developed at relapse only (hazard
      ratio, 3.06; 95% confidence interval: 1.09-8.59; P=0.03). Our results demonstrate
      cytogenetic evolution towards high-risk disease after autologous transplantation
      and underline the importance of repeated genetic testing in relapsed myeloma
      (EudraCT number of the HD4 trial: 2004-000944-26).

PMID- 28495914
TI  - E14a2 BCR-ABL1 transcript is associated with a higher rate of treatment-free
      remission in individuals with chronic myeloid leukemia after stopping tyrosine
      kinase inhibitor therapy.

PMID- 28495915
TI  - Extracellular glycine is necessary for optimal hemoglobinization of erythroid
      cells.
AB  - Vertebrate heme synthesis requires three substrates: succinyl-CoA, which
      regenerates in the tricarboxylic acid cycle, iron and glycine. For each heme
      molecule synthesized, one atom of iron and eight molecules of glycine are needed.
      Inadequate delivery of iron to immature erythroid cells leads to a decreased
      production of heme, but virtually nothing is known about the consequence of an
      insufficient supply of extracellular glycine on the process of hemoglobinization.
      To address this issue, we exploited mice in which the gene encoding glycine
      transporter 1 (GlyT1) was disrupted. Primary erythroid cells isolated from fetal
      livers of GlyT1 knockout (GlyT1-/-) and GlyT1-haplodeficient (GlyT1+/-) embryos
      had decreased cellular uptake of [2-14C]glycine and heme synthesis as revealed by
      a considerable decrease in [2-14C]glycine and 59Fe incorporation into heme. Since
      GlyT1-/- mice die during the first postnatal day, we analyzed blood parameters of
      newborn pups and found that GlyT1-/- animals develop hypochromic microcytic
      anemia. Our finding that Glyt1-deficiency causes decreased heme synthesis in
      erythroblasts is unexpected, since glycine is a non-essential amino acid. It also
      suggests that GlyT1 represents a limiting step in heme and, consequently,
      hemoglobin production.

PMID- 28495916
TI  - Myelodysplasia and liver disease extend the spectrum of RTEL1 related
      telomeropathies.

PMID- 28495917
TI  - Combining flow cytometry and WT1 assessment improves the prognostic value of pre
      transplant minimal residual disease in acute myeloid leukemia.

PMID- 28495920
TI  - The British Cardiovascular Society Annual Conference, Manchester, 5-7 June 2017:
      the Vice-President's message.

PMID- 28495919
TI  - Alternative TSSs are co-regulated in single cells in the mouse brain.
AB  - Alternative transcription start sites (TSSs) have been extensively studied genome
      wide for many cell types and have been shown to be important during development
      and to regulate transcript abundance between cell types. Likewise, single-cell
      gene expression has been extensively studied for many cell types. However, how
      single cells use TSSs has not yet been examined. In particular, it is unknown
      whether alternative TSSs are independently expressed, or whether they are co
      activated or even mutually exclusive in single cells. Here, we use a previously
      published single-cell RNA-seq dataset, comprising thousands of cells, to study
      alternative TSS usage. We find that alternative TSS usage is a regulated process,
      and the correlation between two TSSs expressed in single cells of the same cell
      type is surprisingly high. Our findings indicate that TSSs generally are
      regulated by common factors rather than being independently regulated or
      stochastically expressed.

PMID- 28495921
TI  - Heartbeat: Managing cardiovascular disease as a family of diseases in the
      community.

PMID- 28495918
TI  - Bone marrow morphology is a strong discriminator between chronic eosinophilic
      leukemia, not otherwise specified and reactive idiopathic hypereosinophilic
      syndrome.
AB  - Chronic eosinophilic leukemia, not otherwise specified can be difficult to
      distinguish from idiopathic hypereosinophilic syndrome according to the current
      World Health Organization guideline. To examine whether the morphological
      features of bone marrow might aid in the differential diagnosis of these two
      entities, we studied a total of 139 patients with a diagnosis of chronic
      eosinophilic leukemia, not otherwise specified (n=17) or idiopathic
      hypereosinophilic syndrome (n=122). As a group, abnormal bone marrow
      morphological features, resembling myelodysplastic syndromes, myeloproliferative
      neoplasm or myelodysplastic/myeloproliferative neoplasm, were identified in
      40/139 (27%) patients: 16 (94%) of those with chronic eosinophilic leukemia and
      24 (20%) of those with hypereosinophilic syndrome. Abnormal bone marrow
      correlated with older age (P<0.001), constitutional symptoms (P<0.001), anemia
      (P=0.041), abnormal platelet count (P=0.002), organomegaly (P=0.008), elevated
      lactate dehydrogenase concentration (P=0.005), abnormal karyotype (P<0.001), as
      well as the presence of myeloid neoplasm-related mutations (P<0.001). Patients
      with abnormal bone marrow had shorter survival (48.1 months versus not reached,
      P<0.001), a finding which was independent of other confounding factors (P<0.001).
      The association between abnormal bone marrow and shorter survival was also
      observed in hypereosinophilic syndrome patients alone. In summary, most patients
      with chronic eosinophilic leukemia, not otherwise specified and a proportion of
      those with idiopathic hypereosinophilic syndrome show abnormal bone marrow
      features similar to the ones encountered in patients with myelodysplastic
      syndromes, myelodysplastic/myeloproliferative neoplasm or BCR-ABL1-negative
      myeloproliferative neoplasm. Among patients who are currently considered to have
      idiopathic hypereosinophilic syndrome, abnormal bone marrow is a strong indicator
      of clonal hematopoiesis. Similar to other myeloid neoplasms, bone marrow
      morphology should be one of the major criteria to distinguish patients with
      chronic eosinophilic leukemia, not otherwise specified or clonal
      hypereosinophilic syndrome from those with truly reactive idiopathic
      hypereosinophilic syndrome.

PMID- 28495922
TI  - Rituximab immunotherapy: it's getting personal.

PMID- 28495923
TI  - Neutrophils: positive or negative?

PMID- 28495924
TI  - A mitochondrial drug to treat AML.

PMID- 28495925
TI  - Indoxyl sulfate, a uremic trigger for platelets.

PMID- 28495926
TI  - Mobilizing plasmacytoid dendritic cells.

PMID- 28495927
TI  - An infant with Pearson syndrome: a rare cause of congenital sideroblastic anemia
      and bone marrow failure.

PMID- 28495928
TI  - Cyclin D1-negative blastoid mantle cell lymphoma exhibiting cleaved to bilobated
      cytomorphology.

PMID- 28495931
TI  - Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition.
AB  - OBJECTIVE: An excessive release and impaired degradation of neutrophil
      extracellular traps (NETs) leads to the continuous exposure of NETs to the
      endothelium in a variety of hematologic and autoimmune disorders, including lupus
      nephritis. This study aims to unravel the mechanisms through which NETs
      jeopardize vascular integrity. APPROACH AND RESULTS: Microvascular and
      macrovascular endothelial cells were exposed to NETs, and subsequent effects on
      endothelial integrity and function were determined in vitro and in vivo. We found
      that endothelial cells have a limited capacity to internalize NETs via the
      receptor for advanced glycation endproducts. An overflow of the phagocytic
      capacity of endothelial cells for NETs resulted in the persistent extracellular
      presence of NETs, which rapidly altered endothelial cell-cell contacts and
      induced vascular leakage and transendothelial albumin passage through elastase
      mediated proteolysis of the intercellular junction protein VE-cadherin.
      Furthermore, NET-associated elastase promoted the nuclear translocation of
      junctional beta-catenin and induced endothelial-to-mesenchymal transition in
      cultured endothelial cells. In vivo, NETs could be identified in kidney samples
      of diseased MRL/lpr mice and patients with lupus nephritis, in whom the
      glomerular presence of NETs correlated with the severity of proteinuria and with
      glomerular endothelial-to-mesenchymal transition. CONCLUSIONS: These results
      indicate that an excess of NETs exceeds the phagocytic capacity of endothelial
      cells for NETs and promotes vascular leakage and endothelial-to-mesenchymal
      transition through the degradation of VE-cadherin and the subsequent activation
      of beta-catenin signaling. Our data designate NET-associated elastase as a
      potential therapeutic target in the prevention of endothelial alterations in
      diseases characterized by aberrant NET release.

PMID- 28495929
TI  - Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking.
AB  - OBJECTIVE: Coagulation initiation by tissue factor (TF) is regulated by cellular
      inhibitors, cell surface availability of procoagulant phosphatidylserine, and
      thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a
      noncoagulant state and to generating prothrombotic TF remain incompletely
      understood. APPROACH AND RESULTS: Here, we study the activation of TF in primary
      macrophages by a combination of pharmacological, genetic, and biochemical
      approaches. We demonstrate that primed macrophages effectively control TF cell
      surface activity by receptor internalization. After cell injury, ATP signals
      through the purinergic receptor P2rx7 induce release of TF+ microvesicles. TF
      cell surface availability for release onto microvesicles is regulated by the
      GTPase arf6 associated with integrin alpha4beta1. Furthermore, microvesicles
      proteome analysis identifies activation of Galphai2 as a participating factor in
      the release of microvesicles with prothrombotic activity in flowing blood. ATP
      not only prevents TF and phosphatidylserine internalization but also induces TF
      conversion to a conformation with high affinity for its ligand, coagulation
      factor VII. Although inhibition of dynamin-dependent internalization also exposes
      outer membrane procoagulant phosphatidylserine, the resulting TF+ microvesicles
      distinctly lack protein disulfide isomerase and high affinity TF and fail to
      produce fibrin strands typical for microvesicles generated by thrombo
      inflammatory P2rx7 activation. CONCLUSIONS: These data show that procoagulant
      phospholipid exposure is not sufficient and that TF affinity maturation is
      required to generate prothrombotic microvesicles from a variety of cell types.
      These findings are significant for understanding TF-initiated thrombosis and
      should be considered in designing functional microvesicles-based diagnostic
      approaches.

PMID- 28495930
TI  - ADAMTS13 Retards Progression of Diabetic Nephropathy by Inhibiting Intrarenal
      Thrombosis in Mice.
AB  - OBJECTIVE: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I
      repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic
      ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found
      association between reduced ADAMTS13-specific activity, ultralarge VWF multimers,
      and thrombotic angiopathy in patients with diabetic nephropathy. It remains
      unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a
      causative effect in diabetic nephropathy. APPROACH AND RESULTS: The extent of
      renal injury was evaluated in wild-type (WT), Adamts13-/- and Adamts13-/-Vwf-/-
      mice after 26 weeks of streptozotocin-induced diabetic nephropathy. We found that
      WT diabetic mice exhibited low plasma ADAMTS13-specific activity and increased
      VWF levels (P<0.05 versus WT nondiabetic mice). Adamts13-/- diabetic mice
      exhibited deterioration of kidney function (increased albuminuria, plasma
      creatinine, and urea; P<0.05 versus WT diabetic mice), independent of
      hyperglycemia and hypertension. Deterioration of kidney function in Adamts13-/-
      diabetic mice was concomitant with aggravated intrarenal thrombosis (assessed by
      plasminogen activator inhibitor, VWF, fibrin(ogen), and CD41-positive
      microthrombi), increased mesangial cell expansion, and extracellular matrix
      deposition (P<0.05 versus WT diabetic mice). Genetic deletion of VWF in Adamts13
      /- diabetic mice improved kidney function, inhibited intrarenal thrombosis, and
      alleviated histological changes in glomeruli, suggesting that exacerbation of
      diabetic nephropathy in the setting of ADAMTS13 deficiency is VWF dependent.
      CONCLUSIONS: ADAMTS13 retards progression of diabetic nephropathy, most likely by
      inhibiting VWF-dependent intrarenal thrombosis. Alteration in ADAMTS13-VWF
      balance may be one of the key pathophysiological mechanisms of thrombotic
      angiopathy in diabetes mellitus.

PMID- 28495932
TI  - Effectiveness and Adoption of a Drawing-to-Learn Study Tool for Recall and
      Problem Solving: Minute Sketches with Folded Lists.
AB  - Drawing by learners can be an effective way to develop memory and generate visual
      models for higher-order skills in biology, but students are often reluctant to
      adopt drawing as a study method. We designed a nonclassroom intervention that
      instructed introductory biology college students in a drawing method, minute
      sketches in folded lists (MSFL), and allowed them to self-assess their recall and
      problem solving, first in a simple recall task involving non-European alphabets
      and later using unfamiliar biology content. In two preliminary ex situ
      experiments, students had greater recall on the simple learning task, non
      European alphabets with associated phonetic sounds, using MSFL in comparison with
      a preferred method, visual review (VR). In the intervention, students studying
      using MSFL and VR had ~50-80% greater recall of content studied with MSFL and, in
      a subset of trials, better performance on problem-solving tasks on biology
      content. Eight months after beginning the intervention, participants had shifted
      self-reported use of drawing from 2% to 20% of study time. For a small subset of
      participants, MSFL had become a preferred study method, and 70% of participants
      reported continued use of MSFL. This brief, low-cost intervention resulted in
      enduring changes in study behavior.

PMID- 28495933
TI  - Curriculum Alignment with Vision and Change Improves Student Scientific Literacy.
AB  - The Vision and Change in Undergraduate Biology Education final report challenged
      institutions to reform their biology courses to focus on process skills and
      student active learning, among other recommendations. A large southeastern
      university implemented curricular changes to its majors' introductory biology
      sequence in alignment with these recommendations. Discussion sections focused on
      developing student process skills were added to both lectures and a lab, and one
      semester of lab was removed. This curriculum was implemented using active
      learning techniques paired with student collaboration. This study determined
      whether these changes resulted in a higher gain of student scientific literacy by
      conducting pre/posttesting of scientific literacy for two cohorts: students
      experiencing the unreformed curriculum and students experiencing the reformed
      curriculum. Retention of student scientific literacy for each cohort was also
      assessed 4 months later. At the end of the academic year, scientific literacy
      gains were significantly higher for students in the reformed curriculum (p =
      0.005), with those students having double the scientific literacy gains of the
      cohort in the unreformed curriculum. Retention of scientific literacy did not
      differ between the cohorts.

PMID- 28495934
TI  - How Should I Study for the Exam? Self-Regulated Learning Strategies and
      Achievement in Introductory Biology.
AB  - In college introductory science courses, students are challenged with mastering
      large amounts of disciplinary content while developing as autonomous and
      effective learners. Self-regulated learning (SRL) is the process of setting
      learning goals, monitoring progress toward them, and applying appropriate study
      strategies. SRL characterizes successful, "expert" learners, and develops with
      time and practice. In a large, undergraduate introductory biology course, we
      investigated: 1) what SRL strategies students reported using the most when
      studying for exams, 2) which strategies were associated with higher achievement
      and with grade improvement on exams, and 3) what study approaches students
      proposed to use for future exams. Higher-achieving students, and students whose
      exam grades improved in the first half of the semester, reported using specific
      cognitive and metacognitive strategies significantly more frequently than their
      lower-achieving peers. Lower-achieving students more frequently reported that
      they did not implement their planned strategies or, if they did, still did not
      improve their outcomes. These results suggest that many students entering
      introductory biology have limited knowledge of SRL strategies and/or limited
      ability to implement them, which can impact their achievement. Course-specific
      interventions that promote SRL development should be considered as integral
      pedagogical tools, aimed at fostering development of students' lifelong learning
      skills.

PMID- 28495935
TI  - Metacognition in Upper-Division Biology Students: Awareness Does Not Always Lead
      to Control.
AB  - Students with awareness and control of their own thinking can learn more and
      perform better than students who are not metacognitive. Metacognitive regulation
      is how you control your thinking in order to learn. It includes the skill of
      evaluation, which is the ability to appraise your approaches to learning and then
      modify future plans based on those appraisals. We asked when, why, and how upper
      division biology students evaluated their approaches to learning. We used self
      evaluation assignments to identify students with potentially high metacognition
      and conducted semistructured interviews to collect rich qualitative data from
      them. Through content analysis, we found that students evaluated their approaches
      to learning when their courses presented novel challenges. Most students
      evaluated in response to an unsatisfactory grade. While evaluating study
      strategies, many students considered performance and learning simultaneously. We
      gained insights on the barriers students face when they try to change their
      approaches to learning based on their evaluations. A few students continued to
      use ineffective study strategies even though they were aware of the
      ineffectiveness of those strategies. A desire to avoid feeling uncomfortable was
      the primary reason they avoided strategies that they knew were more effective. We
      examined the behavioral change literature to help interpret these findings.

PMID- 28495936
TI  - ASPECT: A Survey to Assess Student Perspective of Engagement in an Active
      Learning Classroom.
AB  - The primary measure used to determine relative effectiveness of in-class
      activities has been student performance on pre/posttests. However, in today's
      active-learning classrooms, learning is a social activity, requiring students to
      interact and learn from their peers. To develop effective active-learning
      exercises that engage students, it is important to gain a more holistic view of
      the student experience in an active-learning classroom. We have taken a mixed
      methods approach to iteratively develop and validate a 16-item survey to measure
      multiple facets of the student experience during active-learning exercises. The
      instrument, which we call Assessing Student Perspective of Engagement in Class
      Tool (ASPECT), was administered to a large introductory biology class, and
      student responses were subjected to exploratory factor analysis. The 16 items
      loaded onto three factors that cumulatively explained 52% of the variation in
      student response: 1) value of activity, 2) personal effort, and 3) instructor
      contribution. ASPECT provides a rapid, easily administered means to measure
      student perception of engagement in an active-learning classroom. Gaining a
      better understanding of students' level of engagement will help inform instructor
      best practices and provide an additional measure for comprehensively assessing
      the impact of different active-learning strategies.

PMID- 28495937
TI  - An Analysis of the Perceptions and Resources of Large University Classes.
AB  - Large class learning is a reality that is not exclusive to the first-year
      experience at midsized, comprehensive universities; upper-year courses have
      similarly high enrollment, with many class sizes greater than 200 students.
      Research into the efficacy and deficiencies of large undergraduate classes has
      been ongoing for more than 100 years, with most research associating large
      classes with weak student engagement, decreased depth of learning, and
      ineffective interactions. This study used a multidimensional research approach to
      survey student and instructor perceptions of large biology classes and to
      characterize the courses offered by a department according to resources and
      course structure using a categorical principal components analysis. Both student
      and instructor survey results indicated that a large class begins around 240
      students. Large classes were identified as impersonal and classified using
      extrinsic qualifiers; however, students did identify techniques that made the
      classes feel smaller. In addition to the qualitative survey, we also attempted to
      quantify courses by collecting data from course outlines and analyzed the data
      using categorical principal component analysis. The analysis maps institutional
      change in resource allocation and teaching structure from 2010 through 2014 and
      validates the use of categorical principal components analysis in educational
      research. We examine what perceptions and factors are involved in a large class
      that is perceived to feel small. Our analysis suggests that it is not the
      addition of resources or difference in the lecturing method, but it is the
      instructor that determines whether a large class can feel small.

PMID- 28495938
TI  - Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an
      umbrella review.
AB  - BACKGROUND: Allergic rhinitis and asthma are important public health concerns,
      yet there is no consensus about the benefits and harms of allergen-specific
      immunotherapy to treat these conditions. We performed an umbrella review of
      systematic reviews summarizing the current evidence for the benefits and harms of
      subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS:
      We searched MEDLINE, Embase, the Cochrane Library and the grey literature from
      Jan. 1, 2010 to Nov. 20, 2016 for systematic reviews of randomized controlled
      trials or prospectively controlled studies involving children or adults with
      allergic rhinitis or asthma. Outcomes were summarized narratively (benefits:
      total combined symptom-medication score, symptom score, medication score, disease
      specific quality of life, adherence; harms: anaphylaxis, death, local and
      systemic reactions). RESULTS: Twenty-three systematic reviews were included. SCIT
      and SLIT were more effective than placebo for most outcomes. SCIT was better than
      SLIT at improving medication and symptom scores, with no differences in quality
      of life; however, data were limited for this comparison. Anaphylaxis and death
      were infrequently reported. Few reviews assessed benefits or harms among
      children. INTERPRETATION: Allergen immunotherapy appears to be effective among
      patients with allergic rhinitis and asthma. The safety of allergen immunotherapy
      is not conclusively established, although death and anaphylaxis appear to be
      rare. PROSPERO no.: CRD42015024590.

PMID- 28495939
TI  - APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in
      Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline.
AB  - BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the
      strongest currently known genetic risk factor for Alzheimer disease and is
      associated with brain gray matter loss, notably in areas involved in Alzheimer
      disease pathology. Our objective was to assess the effect of APOE*E4 on brain
      structures in healthy elderly controls who subsequently developed subtle
      cognitive decline. MATERIALS AND METHODS: This prospective study included 382
      community-dwelling elderly controls. At baseline, participants underwent MR
      imaging at 3T, extensive neuropsychological testing, and genotyping. After
      neuropsychological follow-up at 18 months, participants were classified into
      cognitively stable controls and cognitively deteriorating controls. Data analysis
      included whole-brain voxel-based morphometry and ROI analysis of GM. RESULTS:
      APOE*E4-related GM loss at baseline was found only in the cognitively
      deteriorating controls in the posterior cingulate cortex. There was no APOE*E4
      related effect in the hippocampus, mesial temporal lobe, or brain areas not
      involved in Alzheimer disease pathology. Controls in the cognitively
      deteriorating group had slightly lower GM concentration in the hippocampus at
      baseline. Higher GM densities in the hippocampus, middle temporal lobe, and
      amygdala were associated with a decreased risk for cognitively deteriorating
      group status at follow-up. CONCLUSIONS: APOE*E4-related GM loss in the posterior
      cingulate cortex (an area involved in Alzheimer disease pathology) was found only
      in those elderly controls who subsequently developed subtle cognitive decline but
      not in cognitively stable controls. This finding might explain the partially
      conflicting results of previous studies that typically did not include detailed
      neuropsychological assessment and follow-up. Most important, APOE*E4 status had
      no impact on GM density in areas affected early by neurofibrillary tangle
      formation such as the hippocampus and mesial temporal lobe.

PMID- 28495940
TI  - Neuroimaging Changes in Menkes Disease, Part 2.
AB  - This is the second part of a retrospective and review MR imaging study aiming to
      define the frequency rate, timing, imaging features, and evolution of gray matter
      changes in Menkes disease, a rare multisystem X-linked disorder of copper
      metabolism characterized by early, severe, and progressive neurologic
      involvement. According to our analysis, neurodegenerative changes and focal basal
      ganglia lesions already appear in the early phases of the disease. Subdural
      collections are less common than generally thought; however, their presence
      remains important because they might challenge the differential diagnosis with
      child abuse and might precipitate the clinical deterioration. Anecdotal findings
      in our large sample seem to provide interesting clues about the protean
      mechanisms of brain injury in this rare disease and further highlight the broad
      spectrum of MR imaging findings that might be expected while imaging a child with
      the suspicion of or a known diagnosis of Menkes disease.

PMID- 28495941
TI  - Pontomesencephalic Atrophy and Postural Instability in Wilson Disease.
AB  - BACKGROUND AND PURPOSE: The MR Parkinsonism index helps in differentiating
      progressive supranuclear palsy from Parkinson disease and multisystem atrophy.
      Pontomesencephalic involvement is common in neurologic Wilson disease, but there
      is no prior study evaluating the MR Parkinsonism index and its indices in Wilson
      disease. We report the MR Parkinsonism index and its indices in Wilson disease
      and correlate these changes with clinical severity and postural reflex. MATERIALS
      AND METHODS: Thirteen individuals with neurologic Wilson disease were included,
      and their clinical details, including neurologic severity, postural reflex
      abnormality, and location of signal changes on MR imaging, were noted. The 3D
      BRAVO T1 sequence was used for measurement of the MR Parkinsonism index and its
      indices. The MR Parkinsonism index and its indices were also obtained in 6 age-
      and sex-matched controls. The morphometric parameters in Wilson disease were
      compared with those in with healthy controls and among the patients with and
      without abnormal postural reflex. RESULTS: The midbrain area was reduced in
      patients with Wilson disease compared with controls (112.08 +/- 27.94 versus
      171.95 +/- 23.66 mm2, P = .002). The patients with an abnormal postural reflex
      had an increased MR Parkinsonism index and pons-to-midbrain ratio compared with
      controls, whereas these parameters were equivalent in patients with normal
      postural reflex and controls. The patients with abnormal postural reflex had more
      severe illness, evidenced by higher Burke-Fahn-Marsden scores (51.0 +/- 32.27
      versus 13.75 +/- 12.37, P = .04) and neurologic severity grades (2.57 +/- 0.53
      versus 1.67 +/- 0.82, P = .04). CONCLUSIONS: An increase in the MR Parkinsonism
      index in Wilson disease is mainly due to midbrain atrophy and it correlates with
      neurologic severity and abnormal postural reflex.

PMID- 28495942
TI  - TIPIC Syndrome: Beyond the Myth of Carotidynia, a New Distinct Unclassified
      Entity.
AB  - BACKGROUND AND PURPOSE: The differential diagnosis of acute cervical pain
      includes nonvascular and vascular causes such as carotid dissection, carotid
      occlusion, or vasculitis. However, some patients present with unclassified
      vascular and perivascular changes on imaging previously reported as carotidynia.
      The aim of our study was to improve the description of this as yet unclassified
      clinico-radiologic entity. MATERIALS AND METHODS: From January 2009 through April
      2016, 47 patients from 10 centers presenting with acute neck pain or tenderness
      and at least 1 cervical image showing unclassified carotid abnormalities were
      included. We conducted a systematic, retrospective study of their medical charts
      and diagnostic and follow-up imaging. Two neuroradiologists independently
      analyzed the blinded image datasets. RESULTS: The median patient age was 48
      years. All patients presented with acute neck pain, and 8 presented with
      transient neurologic symptoms. Imaging showed an eccentric pericarotidian
      infiltration in all patients. An intimal soft plaque was noted in 16 patients,
      and a mild luminal narrowing was noted in 16 patients. Interreader
      reproducibility was excellent. All patients had complete pain resolution within a
      median of 13 days. At 3-month follow-up, imaging showed complete disappearance of
      vascular abnormalities in 8 patients, and a marked decrease in all others.
      CONCLUSIONS: Our study improved the description of an unclassified, clinico
      radiologic entity, which could be described by the proposed acronym: TransIent
      Perivascular Inflammation of the Carotid artery (TIPIC) syndrome.

PMID- 28495943
TI  - Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis:
      Retrospective Analysis of an 18-Year Longitudinal Study.
AB  - BACKGROUND AND PURPOSE: Gadolinium-based contrast agents have been associated
      with lasting high T1-weighted signal intensity in the dentate nucleus and globus
      pallidus, with histopathologically confirmed gadolinium retention. We aimed to
      longitudinally investigate the relationship of multiple gadolinium-based contrast
      agent administrations to the Signal Intensity Index in the dentate nucleus and
      globus pallidus and any associations with cognitive function in multiple
      sclerosis. MATERIALS AND METHODS: The Signal Intensity Index in the dentate
      nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR
      imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving
      multiple gadolinium-based contrast agent administrations and 23 healthy age- and
      sex-matched controls. Participants also underwent comprehensive
      neuropsychological testing. RESULTS: Patients with MS had a higher Signal
      Intensity Index in the dentate nucleus (P < .001), but not in the globus pallidus
      (P = .19), compared with non-gadolinium-based contrast agent-exposed healthy
      controls by an unpaired t test. Increasing numbers of gadolinium-based contrast
      agent administrations were associated with an increased Signal Intensity Index in
      the dentate nucleus (beta = 0.45, P < .001) and globus pallidus (beta = 0.60, P <
      .001). This association remained stable with corrections for the age, disease
      duration, and physical disability for both the dentate nucleus (beta = 0.43, P =
      .001) and globus pallidus (beta = 0.58, P < .001). An increased Signal Intensity
      Index in the dentate nucleus among patients with MS was associated with lower
      verbal fluency scores, which remained significant after correction for several
      aspects of disease severity (beta = -0.40 P = .013). CONCLUSIONS: Our data
      corroborate previous reports of lasting gadolinium retention in brain tissues. An
      increased Signal Intensity Index in the dentate nucleus and globus pallidus was
      associated with lower verbal fluency, which does not prove causality but
      encourages further studies on cognition and gadolinium-based contrast agent
      administration.

PMID- 28495944
TI  - What Does the Boxed Warning Tell Us? Safe Practice of Using Ferumoxytol as an MRI
      Contrast Agent.
AB  - BACKGROUND AND PURPOSE: Despite the label change and the FDA's boxed warning
      added to the Feraheme (ferumoxytol) label in March 2015, radiologists have shown
      increasing interest in using ferumoxytol as an MR imaging contrast agent as a
      supplement or alternative to gadolinium. The goals of this study were to provide
      information regarding ferumoxytol safety as an imaging agent in a single center
      and to assess how the Feraheme label change may affect this potential, currently
      off-label indication. MATERIALS AND METHODS: This retrospective study evaluated
      the overall frequency of ferumoxytol-related adverse events when used for CNS MR
      imaging. Patients with various CNS pathologies were enrolled in institutional
      review board-approved imaging studies. Ferumoxytol was administered as multiple
      rapid bolus injections. The risk of adverse events was correlated with
      demographic data/medical history. RESULTS: The safety of 671 ferumoxytol-enhanced
      MR studies in 331 patients was analyzed. No anaphylactic, life-threatening, or
      fatal (grade 4 or 5) adverse events were recorded. The overall proportion of
      ferumoxytol-related grade 1-3 adverse events was 10.6% (8.6% occurring within 48
      hours), including hypertension (2.38%), nausea (1.64%), diarrhea (1.04%), and
      headache (1.04%). History of 1 or 2 allergies was associated with an increased
      risk of adverse events (14.61% versus 7.51% [no history]; P = .007). CONCLUSIONS:
      The frequency of mild ferumoxytol-related adverse events was comparable with
      literature results, and no serious adverse event was recorded. Although the
      recommendations in the boxed warning should be followed, serious adverse events
      appear to be rare, and with proper precautions, ferumoxytol may be a valuable MR
      imaging agent.

PMID- 28495945
TI  - Role of High-Resolution Dynamic Contrast-Enhanced MRI with Golden-Angle Radial
      Sparse Parallel Reconstruction to Identify the Normal Pituitary Gland in Patients
      with Macroadenomas.
AB  - BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with
      imaging in patients with macroadenomas has been inadequately explored. The
      pituitary gland enhancing more avidly than a macroadenoma has been described in
      the literature. Taking advantage of this differential enhancement pattern, our
      aim was to evaluate the role of high-resolution dynamic MR imaging with golden
      angle radial sparse parallel reconstruction in localizing the pituitary gland in
      patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND
      METHODS: A retrospective study was performed in 17 patients who underwent trans
      sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated
      brain examination sequences with golden-angle radial sparse parallel technique
      were obtained. Using an ROI-based method to obtain signal-time curves and
      permeability measures, 3 separate readers identified the normal pituitary gland
      distinct from the macroadenoma. The readers' localizations were then compared
      with the intraoperative location of the gland. Statistical analyses were
      performed to assess the interobserver agreement and correlation with operative
      findings. RESULTS: The normal pituitary gland was found to have steeper
      enhancement-time curves as well as higher peak enhancement values compared with
      the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3
      planes (kappa = 0.89). In the 14 cases in which the gland was clearly identified
      intraoperatively, the correlation between the readers' localization and the true
      location derived from surgery was also nearly perfect (kappa = 0.95).
      CONCLUSIONS: This study confirms our ability to consistently and accurately
      identify the normal pituitary gland in patients with macroadenomas with the
      golden-angle radial sparse parallel technique with quantitative permeability
      measurements and enhancement-time curves.

PMID- 28495946
TI  - Neuroimaging Changes in Menkes Disease, Part 1.
AB  - Menkes disease is a rare multisystem X-linked disorder of copper metabolism.
      Despite an early, severe, and progressive neurologic involvement, our knowledge
      of brain involvement remains unsatisfactory. The first part of this retrospective
      and review MR imaging study aims to define the frequency rate, timing, imaging
      features, and evolution of intracranial vascular and white matter changes.
      According to our analysis, striking but also poorly evolutive vascular
      abnormalities characterize the very early phases of disease. After the first
      months, myelination delay becomes evident, often in association with protean
      focal white matter lesions, some of which reveal an age-specific brain
      vulnerability. In later phases of the disease, concomitant progressive
      neurodegeneration might hinder the myelination progression. The currently
      enriched knowledge of neuroradiologic finding evolution provides valuable clues
      for early diagnosis, identifies possible MR imaging biomarkers of new treatment
      efficacy, and improves our comprehension of possible mechanisms of brain injury
      in Menkes disease.

PMID- 28495948
TI  - Introduction of a Dedicated Emergency Department MR Imaging Scanner at the Barrow
      Neurological Institute.
AB  - Use of advanced imaging in the emergency department has been increasing in the
      United States during the past 2 decades. This trend has been most notable in CT,
      which has increased concern over the effects of increasing levels of medical
      ionizing radiation. MR imaging offers a safe, nonionizing alternative to CT and
      is diagnostically superior in many neurologic conditions encountered in the
      emergency department. Herein, we describe the process of developing and
      installing a dedicated MR imaging scanner in the Neuroscience Emergency
      Department at the Barrow Neurological Institute and its effects on neuroradiology
      and the emergency department in general.

PMID- 28495947
TI  - Mechanical Thrombectomy with the Embolus Retriever with Interlinked Cages in
      Acute Ischemic Stroke: ERIC, the New Boy in the Class.
AB  - BACKGROUND AND PURPOSE: The Embolus Retriever with Interlinked Cages (ERIC)
      device is a novel stent retriever for mechanical thrombectomy. It consists of
      interlinked cages and could improve procedural benchmarks and clinical outcome
      compared with classic stent retrievers. This study compares the rates of
      recanalization, favorable clinical outcome, procedural adverse events, and
      benchmarks between the ERIC device and classic stent retrievers. MATERIALS AND
      METHODS: From 545 patients treated with thrombectomy between 2012 and 2015, 316
      patients were included. The mean age was 69 +/-13 years, the mean baseline NIHSS
      score was 17 +/- 5, and 174 (55%) were men. The ERIC was used as the primary
      thrombectomy device in 59 (19%) patients. In a propensity score matched analysis
      including the NIHSS score, clot location, delay to groin puncture,
      neurointerventionalist, and anesthetic management, 57 matched pairs were
      identified. RESULTS: Patients treated with the ERIC device compared with classic
      stent retrievers showed equal rates of recanalization (86% versus 81%, P = .61),
      equal favorable 3-month clinical outcome (mRS 0-2: 46% versus 40%, P = .71), and
      procedural adverse events (28% versus 30%, P = 1.00). However, in patients
      treated with the ERIC device, thrombectomy procedures were less time-consuming
      (67 versus 98 minutes, P = .009) and a rescue device was needed less often (18%
      versus 39%, P = .02) compared with classic stent retrievers. CONCLUSIONS:
      Mechanical thrombectomy with the ERIC device is effective and safe. Rates of
      favorable procedural and clinical outcomes are at least as good as those with
      classic stent retrievers. Of note, the ERIC device might be time-saving and
      decrease the need for rescue devices. These promising results call for
      replication in larger prospective clinical trials.

PMID- 28495949
TI  - The Central Bright Spot Sign: A Potential New MR Imaging Sign for the Early
      Diagnosis of Anterior Ischemic Optic Neuropathy due to Giant Cell Arteritis.
AB  - BACKGROUND AND PURPOSE: A rapid identification of the etiology of anterior
      ischemic optic neuropathy is crucial because it determines therapeutic
      management. Our aim was to assess MR imaging to study the optic nerve head in
      patients referred with anterior ischemic optic neuropathy, due to either giant
      cell arteritis or the nonarteritic form of the disease, compared with healthy
      subjects. MATERIALS AND METHODS: Fifteen patients with giant cell arteritis
      related anterior ischemic optic neuropathy and 15 patients with nonarteritic
      anterior ischemic optic neuropathy from 2 medical centers were prospectively
      included in our study between August 2015 and May 2016. Fifteen healthy subjects
      and patients had undergone contrast-enhanced, flow-compensated, 3D T1-weighted MR
      imaging. The bright spot sign was defined as optic nerve head enhancement with a
      3-grade ranking system. Two radiologists and 1 ophthalmologist independently
      performed blinded evaluations of MR imaging sequences with this scale.
      Statistical analysis included interobserver agreement. RESULTS: MR imaging scores
      were significantly higher in patients with giant cell arteritis-related anterior
      ischemic optic neuropathy than in patients with nonarteritic anterior ischemic
      optic neuropathy (P <= .05). All patients with giant cell arteritis-related
      anterior ischemic optic neuropathy (15/15) and 7/15 patients with nonarteritic
      anterior ischemic optic neuropathy presented with the bright spot sign. No
      healthy subjects exhibited enhancement of the anterior part of the optic nerve.
      There was a significant relationship between the side of the bright spot and the
      side of the anterior ischemic optic neuropathy (P <= .001). Interreader agreement
      was good for observers (kappa = 0.815). CONCLUSIONS: Here, we provide evidence of
      a new MR imaging sign that identifies the acute stage of giant cell arteritis
      related anterior ischemic optic neuropathy; patients without this central bright
      spot sign always had a nonarteritic pathophysiology and therefore did not require
      emergency corticosteroid therapy.

PMID- 28495950
TI  - Carotid Bulb Webs as a Cause of "Cryptogenic" Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Carotid webs are intraluminal shelf-like filling defects
      at the carotid bulb with recently recognized implications in patients with
      recurrent ischemic stroke. We sought to determine whether carotid webs are an
      under-recognized cause of "cryptogenic" ischemic stroke and to estimate their
      prevalence in the general population. MATERIALS AND METHODS: A retrospective
      review of neck CTA studies in young patients with cryptogenic stroke over the
      past 6 years (n = 33) was performed to determine the prevalence of carotid webs
      compared with a control group of patients who received neck CTA studies for
      reasons other than ischemic stroke (n = 63). RESULTS: The prevalence of carotid
      webs in the cryptogenic stroke population was 21.2% (95% CI, 8.9%-38.9%).
      Patients with symptomatic carotid webs had a mean age of 38.9 years (range, 30-48
      years) and were mostly African American (86%) and women (86%). In contrast, only
      1.6% (95% CI, 0%-8.5%) of patients in the control group demonstrated a web. Our
      findings demonstrate a statistically significant association between carotid webs
      and ischemic stroke (OR = 16.7; 95% CI, 2.78-320.3; P = .01). CONCLUSIONS:
      Carotid webs exhibit a strong association with ischemic stroke, and their
      presence should be suspected in patients lacking other risk factors, particularly
      African American women.

PMID- 28495951
TI  - Biochemical analysis of cerebrospinal fluid in the laboratories of deployed
      medical treatment facilities: are Multistix 10 SG strip and iSTAT useful?
AB  - INTRODUCTION: During military deployment, the diagnosis and the management of
      acute bacterial meningitis can be problematic, as deployed Medical Treatment
      Facilities (MTFs) often have a limited laboratory diagnostic capability. However,
      French Role 2 and 3 MTFs have point-of-care (POC) testing to perform urinary
      (Multistix 10 SG strip) and blood (iSTAT handheld analyser) biochemical testing
      mentioned in AMedP8.5. The purpose of this study was to compare the accuracy of
      this urine test strip and of the iSTAT CHEM8 and CG4 cartridges with a standard
      hospital bench top analyser in order to determine if these POC devices have a
      potential role in the biochemical analysis of cerebrospinal fluid (CSF protein,
      CSF glucose and CSF lactate, respectively). METHODS: Agreement between the index
      methods and the reference methods (suitable kits on the Cobas 6 000 System) was
      evaluated by parallel testing of 30 CSF samples by both techniques. For CSF
      protein, agreement between the strip and the reference method was evaluated
      determining the kappa coefficient. For CSF glucose and CSF lactate subgroups,
      least squares linear regressions were calculated and Bland-Altman analyses were
      performed. RESULTS: The Multistix 10 SG strip can be used to make a
      semiquantitative determination of CSF protein. A good agreement between the strip
      and the reference method was observed (kappa coefficient: 0.93 (IC95 0.82 to 1)).
      This strip is thus well adapted to demonstrate an elevation of CSF protein level
      as observed in acute bacterial meningitis. The iSTAT CHEM8 and CG4+ cartridges
      correlated well with the reference methods for the determination of CSF glucose
      and CSF lactate, respectively (r2>0.98) but exhibited a negative bias (~ -7% and
      ~ -15%, respectively). CONCLUSIONS: The combined use of the Multistix 10 SG strip
      and of the iSTAT system appears to be an attractive solution for the biochemical
      investigation of CSF in medical treatment facilities with limited laboratory
      diagnostic capability.

PMID- 28495952
TI  - Deep and profound hypothermia in haemorrhagic shock, friend or foe? A systematic
      review.
AB  - INTRODUCTION: Survival in exsanguinating cardiac arrest patients is poor, as is
      neurological outcome in survivors. Hypothermia has traditionally been seen as
      harmful to trauma patients and associated with increased mortality; however,
      there has been speculation that cooling to very low temperatures (<=20 degrees C)
      could be used to treat haemorrhagic trauma patients by the induction of a
      suspended animation period through extreme cooling, which improves survival and
      preserves neurological function. This has been termed emergency preservation and
      resuscitation (EPR). METHODS: A systematic review of the literature was used to
      examine the evidence base behind the use of deep and profound hypothermia in
      haemorrhagic shock (HS). It included original research articles (human or animal)
      with cooling to <=20 degrees C after HS or an experimental model replicating it.
      Normovolaemic cardiac arrest, central nervous system injury and non-HS models
      were excluded. RESULTS: Twenty articles using 456 animal subjects were included,
      in which 327 were cooled to <=20 degrees C. All studies describing good survival
      rates were possible using EPR and 19/20 demonstrated that EPR can preserve
      neurological function after prolonged periods of circulatory arrest or minimal
      circulatory flow. This additional period can be used for surgical intervention to
      arrest haemorrhage in HS that would otherwise be lethal. CONCLUSIONS: The
      outcomes of this review have significant implications for application to human
      patients and the ongoing human clinical trial (EPR for Cardiac Arrest from
      Trauma). Current evidence suggests that hypothermia <=20 degrees C used in the
      form of EPR could be beneficial to the HS patient.

PMID- 28495954
TI  - The Heavy Heart: Metabolic Mechanisms and Myocardial Mechanics.

PMID- 28495955
TI  - Anisakiasis: a growing cause of abdominal pain!

PMID- 28495953
TI  - Cardiometabolic Traits and Systolic Mechanics in the Community.
AB  - BACKGROUND: Obesity and cardiometabolic dysfunction are associated with increased
      risk of heart failure and other cardiovascular diseases. We sought to examine the
      association of cardiometabolic traits with left ventricular (LV) cardiac
      mechanics. We hypothesized that specific obesity-related phenotypes are
      associated with distinct aspects of LV strain. METHODS AND RESULTS: We evaluated
      the associations of obesity-related phenotypes, including central adiposity,
      diabetes mellitus, insulin resistance, and circulating adipokine concentrations
      with echocardiographic measures of LV mechanical function among participants of
      the Framingham Heart Study Offspring and Third Generation cohorts. Among 6231
      participants, the mean age was 51+/-16 years, and 54% were women. Greater body
      mass index was associated with worse LV longitudinal strain, radial strain
      (apical view), and longitudinal synchrony (multivariable-adjusted P<0.0001).
      After accounting for body mass index, we found that central adiposity, as
      measured by waist circumference, was associated with worse global longitudinal
      strain and synchrony (P<=0.006). Measures of insulin resistance, dyslipidemia,
      and diabetes mellitus also were associated with distinct aspects of LV mechanical
      function. Circulating leptin concentrations were associated with global
      longitudinal and radial strain (apical view, P<0.0001), whereas no such
      association was found with leptin receptor, adiponectin, or C-reactive protein.
      CONCLUSIONS: Our findings highlight the association of central obesity and
      related cardiometabolic phenotypes above and beyond body mass index with
      subclinical measures of LV mechanical function. Interestingly, obesity-related
      traits were associated with distinct aspects of LV mechanics, underscoring
      potential differential effects along specific LV planes of deformation. These
      findings may shed light onto obesity-related cardiac remodeling and heart
      failure.

PMID- 28495956
TI  - Sharing of Genes and Pathways Across Complex Phenotypes: A Multilevel Genome-Wide
      Analysis.
AB  - Evidence from genome-wide association studies (GWAS) suggest that pleiotropic
      effects on human complex phenotypes are very common. Recently, an atlas of
      genetic correlations among complex phenotypes has broadened our understanding of
      human diseases and traits. Here, we examine genetic overlap, from a gene-centric
      perspective, among the same 24 phenotypes previously investigated for genetic
      correlations. After adopting the multilevel pipeline (freely available at
      http://grass.cgs.hku.hk/limx/kgg/), which includes intragenic single nucleotide
      polymorphisms (SNPs), genes, and gene-sets, to estimate genetic similarities
      across phenotypes, a large amount of sharing of several biologically related
      phenotypes was confirmed. In addition, significant genetic overlaps were also
      found among phenotype pairs that were previously unidentified by SNP-level
      approaches. All these pairs with new genetic links are supported by earlier
      epidemiological evidence, although only a few of them have pleiotropic genes in
      the GWAS Catalog. Hence, our gene and gene-set analyses are able to provide new
      insights into cross-phenotype connections. The investigation on genetic sharing
      at three different levels presents a complementary picture of how common DNA
      sequence variations contribute to disease comorbidities and trait manifestations.

PMID- 28495957
TI  - Resolving the Complex Genetic Basis of Phenotypic Variation and Variability of
      Cellular Growth.
AB  - In all organisms, the majority of traits vary continuously between individuals.
      Explaining the genetic basis of quantitative trait variation requires
      comprehensively accounting for genetic and nongenetic factors as well as their
      interactions. The growth of microbial cells can be characterized by a lag
      duration, an exponential growth phase, and a stationary phase. Parameters that
      characterize these growth phases can vary among genotypes (phenotypic variation),
      environmental conditions (phenotypic plasticity), and among isogenic cells in a
      given environment (phenotypic variability). We used a high-throughput microscopy
      assay to map genetic loci determining variation in lag duration and exponential
      growth rate in growth rate-limiting and nonlimiting glucose concentrations, using
      segregants from a cross of two natural isolates of the budding yeast,
      Saccharomyces cerevisiae We find that some quantitative trait loci (QTL) are
      common between traits and environments whereas some are unique, exhibiting gene
      by-environment interactions. Furthermore, whereas variation in the central
      tendency of growth rate or lag duration is explained by many additive loci,
      differences in phenotypic variability are primarily the result of genetic
      interactions. We used bulk segregant mapping to increase QTL resolution by
      performing whole-genome sequencing of complex mixtures of an advanced intercross
      mapping population grown in selective conditions using glucose-limited
      chemostats. We find that sequence variation in the high-affinity glucose
      transporter HXT7 contributes to variation in growth rate and lag duration. Allele
      replacements of the entire locus, as well as of a single polymorphic amino acid,
      reveal that the effect of variation in HXT7 depends on genetic, and allelic,
      background. Amplifications of HXT7 are frequently selected in experimental
      evolution in glucose-limited environments, but we find that HXT7 amplifications
      result in antagonistic pleiotropy that is absent in naturally occurring variants
      of HXT7 Our study highlights the complex nature of the genotype-to-phenotype map
      within and between environments.

PMID- 28495958
TI  - Maternal Torso-Like Coordinates Tissue Folding During Drosophila Gastrulation.
AB  - The rapid and orderly folding of epithelial tissue during developmental processes
      such as gastrulation requires the precise coordination of changes in cell shape.
      Here, we report that the perforin-like protein Torso-like (Tsl), the key
      extracellular determinant for Drosophila embryonic terminal patterning, also
      functions to control epithelial morphogenesis. We find that tsl null mutants
      display a ventral cuticular hole phenotype that is independent of the loss of
      terminal structures, and arises as a consequence of mesoderm invagination
      defects. We show that the holes are caused by uncoordinated constriction of
      ventral cell apices, resulting in the formation of an incomplete ventral furrow.
      Consistent with these data, we find that loss of tsl is sensitive to gene dosage
      of RhoGEF2, a critical mediator of Rho1-dependent ventral cell shape changes
      during furrow formation, suggesting that Tsl may act in this pathway. In
      addition, loss of tsl strongly suppressed the effects of ectopic expression of
      Folded Gastrulation (Fog), a secreted protein that promotes apical constriction.
      Taken together, our data suggest that Tsl controls Rho1-mediated apical
      constriction via Fog. Therefore, we propose that Tsl regulates extracellular Fog
      activity to synchronize cell shape changes and coordinate ventral morphogenesis
      in Drosophila Identifying the Tsl-mediated event that is common to both terminal
      patterning and morphogenesis will be valuable for our understanding of the
      extracellular control of developmental signaling by perforin-like proteins.

PMID- 28495959
TI  - Potential Nematode Alarm Pheromone Induces Acute Avoidance in Caenorhabditis
      elegans.
AB  - It is crucial for animal survival to detect dangers such as predators. A good
      indicator of dangers is injury of conspecifics. Here we show that fluids released
      from injured conspecifics invoke acute avoidance in both free-living and
      parasitic nematodes. Caenorhabditis elegans avoids extracts from closely related
      nematode species but not fruit fly larvae. The worm extracts have no impact on
      animal lifespan, suggesting that the worm extract may function as an alarm
      instead of inflicting physical harm. Avoidance of the worm extract requires the
      function of a cGMP signaling pathway that includes the cGMP-gated channel TAX
      2/TAX-4 in the amphid sensory neurons ASI and ASK. Genetic evidence indicates
      that the avoidance behavior is modulated by the neurotransmitters GABA and
      serotonin, two common targets of anxiolytic drugs. Together, these data support a
      model that nematodes use a nematode-specific alarm pheromone to detect
      conspecific injury.

PMID- 28495960
TI  - Inferring the Joint Demographic History of Multiple Populations: Beyond the
      Diffusion Approximation.
AB  - Understanding variation in allele frequencies across populations is a central
      goal of population genetics. Classical models for the distribution of allele
      frequencies, using forward simulation, coalescent theory, or the diffusion
      approximation, have been applied extensively for demographic inference, medical
      study design, and evolutionary studies. Here we propose a tractable model of
      ordinary differential equations for the evolution of allele frequencies that is
      closely related to the diffusion approximation but avoids many of its limitations
      and approximations. We show that the approach is typically faster, more
      numerically stable, and more easily generalizable than the state-of-the-art
      software implementation of the diffusion approximation. We present a number of
      applications to human sequence data, including demographic inference with a five
      population joint frequency spectrum and a discussion of the robustness of the out
      of-Africa model inference to the choice of modern population.

PMID- 28495961
TI  - An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the
      Aging Drosophila Brain.
AB  - Mutations in the Presenilin genes are the major genetic cause of Alzheimer's
      disease. Presenilin and Nicastrin are essential components of gamma-secretase, a
      multi-subunit protease that cleaves Type I transmembrane proteins. Genetic
      studies in mice previously demonstrated that conditional inactivation of
      Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results
      in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The
      roles of Drosophila Presenilin (Psn) and Nicastrin (Nct) in the adult fly brain,
      however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the
      adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these
      shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype
      that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore,
      expression of these shRNAs in the wing disc caused notching wing phenotypes,
      which are also shared with Psn and Nct mutants. Similar to Nct, neuron-specific
      Psn KD using two independent shRNA lines led to early mortality and rough eye
      phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional
      KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80ts
      system caused shortened lifespan, climbing defects, increases in apoptosis, and
      age-dependent neurodegeneration. Together, these findings demonstrate that,
      similar to their mammalian counterparts, Drosophila Psn and Nct are required for
      neuronal survival during aging and normal lifespan, highlighting an
      evolutionarily conserved role of Presenilin in neuronal protection in the aging
      brain.

PMID- 28495962
TI  - Dietary supplementation of heat-treated Gracilaria and Ulva seaweeds enhanced
      acute hypoxia tolerance in gilthead sea bream (Sparus aurata).
AB  - Intensive aquaculture practices involve rearing fish at high densities. In these
      conditions, fish may be exposed to suboptimal dissolved O2 levels with an
      increased formation of reactive O2 species (ROS) in tissues. Seaweeds (SW)
      contain biologically active substances with efficient antioxidant capacities.
      This study evaluated the effects of dietary supplementation of heat-treated SW
      (5% Gracilaria vermiculophylla or 5% Ulva lactuca) on stress bioindicators in sea
      bream subjected to a hypoxic challenge. 168 fish (104.5 g average weight) were
      distributed in 24 tanks, in which eight tanks were fed one of three experimental
      diets for 34 days: (i) a control diet without SW supplementation, (ii) a control
      diet supplemented with Ulva, or (iii) a control diet with Gracilaria Thereafter,
      fish from 12 tanks (n=4 tanks/dietary treatment) were subjected to 24 h hypoxia
      (1.3 mg O2 l-1) and subsequent recovery normoxia (8.6 mg O2 l-1). Hypoxic fish
      showed an increase in hematocrit values regardless of dietary treatment. Dietary
      modulation of the O2-carrying capacity was conspicuous during recovery, as fish
      fed SW supplemented diets displayed significantly higher haemoglobin
      concentration than fish fed the control diet. After the challenge, survival rates
      in both groups of fish fed SW were higher, which was consistent with a decrease
      in hepatic lipid peroxidation in these groups. Furthermore, the hepatic
      antioxidant enzyme activities were modulated differently by changes in
      environmental O2 condition, particularly in sea bream fed the Gracilaria diet.
      After being subjected to hypoxia, the gene expression of antioxidant enzymes and
      molecular chaperones in liver and heart were down regulated in sea bream fed SW
      diets. This study suggests that the antioxidant properties of heat-treated SW may
      have a protective role against oxidative stress. The nature of these compounds
      and possible mechanisms implied are currently being investigated.

PMID- 28495963
TI  - Arabidopsis DNA topoisomerase I alpha is required for adaptive response to light
      and flower development.
AB  - DNA topoisomerase I alpha (TOP1alpha) plays a specific role in Arabidopsis
      thaliana development and is required for stem cell regulation in shoot and floral
      meristems. Recently, a new role independent of meristem functioning has been
      described for TOP1alpha, namely flowering time regulation. The same feature had
      been detected by us earlier for fas5, a mutant allele of TOP1alpha In this study
      we clarify the effects of fas5 on bolting initiation and analyze the molecular
      basis of its role on flowering time regulation. We show that fas5 mutation leads
      to a constitutive shade avoidance syndrome, accompanied by leaf hyponasty,
      petiole elongation, lighter leaf color and early bolting. Other alleles of
      TOP1alpha demonstrate the same shade avoidance response. RNA sequencing confirmed
      the activation of shade avoidance gene pathways in fas5 mutant plants. It also
      revealed the repression of many genes controlling floral meristem identity and
      organ morphogenesis. Our research further expands the knowledge of TOP1alpha
      function in plant development and reveals that besides stem cell maintenance
      TOP1alpha plays an important new role in regulating the adaptive plant response
      to light stimulus and flower development.

PMID- 28495964
TI  - Transition zone cells reach G2 phase before initiating elongation in maize root
      apex.
AB  - Root elongation requires cell divisions in the meristematic zone and cell
      elongation in the elongation zone. The boundary between dividing and elongating
      cells is called the transition zone. In the meristem zone, initial cells are
      continuously dividing, but on the basal side of the meristem cells exit the
      meristem through the transition zone and enter in the elongation zone, where they
      stop division and rapidly elongate. Throughout this journey cells are accompanied
      by changes in cell cycle progression. Flow cytometry analysis showed that
      meristematic cells are in cycle, but exit when they enter the elongation zone. In
      addition, the percentage of cells in G2 phase (4C) strongly increased from the
      meristem to the elongation zone. However, we did not observe remarkable changes
      in the percentage of cells in cell cycle phases along the entire elongation zone.
      These results suggest that meristematic cells in maize root apex stop the cell
      cycle in G2 phase after leaving the meristem.

PMID- 28495965
TI  - Pias3 is necessary for dorso-ventral patterning and visual response of retinal
      cones but is not required for rod photoreceptor differentiation.
AB  - Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding
      specification of rod and cone photoreceptors through post-translational
      modification of key retinal transcription factors. To investigate its role during
      retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted
      in complete loss of the Pias3 protein. Pias3-/- mice did not show any overt
      phenotype, and retinal lamination appeared normal even at 18 months. We detected
      reduced photopic b-wave amplitude by electroretinography following green light
      stimulation of postnatal day (P)21 Pias3-/- retina, suggesting a compromised
      visual response of medium wavelength (M) cones. No change was evident in response
      of short wavelength (S) cones or rod photoreceptors until 7 months. Increased S
      opsin expression in the M-cone dominant dorsal retina suggested altered
      distribution of cone photoreceptors. Transcriptome profiling of P21 and 18-month
      old Pias3-/- retina revealed aberrant expression of a subset of photoreceptor
      genes. Our studies demonstrate functional redundancy in SUMOylation-associated
      transcriptional control mechanisms and identify a specific, though limited, role
      of Pias3 in modulating spatial patterning and optimal function of cone
      photoreceptor subtypes in the mouse retina.

PMID- 28495966
TI  - Lynn Margulis and the endosymbiont hypothesis: 50 years later.
AB  - The 1967 article "On the Origin of Mitosing Cells" in the Journal of Theoretical
      Biology by Lynn Margulis (then Lynn Sagan) is widely regarded as stimulating
      renewed interest in the long-dormant endosymbiont hypothesis of organelle
      origins. In her article, not only did Margulis champion an endosymbiotic origin
      of mitochondria and plastids from bacterial ancestors, but she also posited that
      the eukaryotic flagellum (undulipodium in her usage) and mitotic apparatus
      originated from an endosymbiotic, spirochete-like organism. In essence, she
      presented a comprehensive symbiotic view of eukaryotic cell evolution
      (eukaryogenesis). Not all of the ideas in her article have been accepted, for
      want of compelling evidence, but her vigorous promotion of the role of symbiosis
      in cell evolution unquestionably had a major influence on how subsequent
      investigators have viewed the origin and evolution of mitochondria and plastids
      and the eukaryotic cell per se.

PMID- 28495967
TI  - Streptococcus pneumoniae capsular polysaccharide is linked to peptidoglycan via a
      direct glycosidic bond to beta-D-N-acetylglucosamine.
AB  - For many bacteria, including those important in pathogenesis, expression of a
      surface-localized capsular polysaccharide (CPS) can be critical for survival in
      host environments. In Gram-positive bacteria, CPS linkage is to either the
      cytoplasmic membrane or the cell wall. Despite the frequent occurrence and
      essentiality of these polymers, the exact nature of the cell wall linkage has not
      been described in any bacterial species. Using the Streptococcus pneumoniae
      serotype 2 CPS, which is synthesized by the widespread Wzy mechanism, we found
      that linkage occurs via the reducing end glucose of CPS and the beta-D-N
      acetylglucosamine (GlcNAc) residues of peptidoglycan (PG). Hydrofluoric acid
      resistance, 31P-NMR, and 32P labeling demonstrated the lack of phosphodiester
      bonds, which typically occur in PG-polysaccharide linkages. Component sugar
      analysis of purified CPS-PG identified only CPS and PG sugars in the appropriate
      ratios, suggesting the absence of an oligosaccharide linker. Time of flight mass
      spectrometry confirmed a direct glycosidic linkage between CPS and PG and showed
      that a single CPS repeat unit can be transferred to PG. The linkage was
      acetolysis susceptible, indicative of a 1,6 glycosidic bond between CPS and the
      GlcNAc C-6. The acetylation state of GlcNAc did not affect linkage. A direct
      glycosidic linkage to PG was also demonstrated for serotypes 8 and 31, whose
      reducing end sugars are glucose and galactose, respectively. These results
      provide the most detailed descriptions of CPS-PG linkages for any microorganism.
      Identification of the linkage is a first step toward identifying the linking
      enzyme and potential inhibitors of its activity.

PMID- 28495968
TI  - Laboratory measurements of HDO/H2O isotopic fractionation during ice deposition
      in simulated cirrus clouds.
AB  - The stable isotopologues of water have been used in atmospheric and climate
      studies for over 50 years, because their strong temperature-dependent
      preferential condensation makes them useful diagnostics of the hydrological
      cycle. However, the degree of preferential condensation between vapor and ice has
      never been directly measured at temperatures below 233 K (-40  degrees C),
      conditions necessary to form cirrus clouds in the Earth's atmosphere, routinely
      observed in polar regions, and typical for the near-surface atmospheric layers of
      Mars. Models generally assume an extrapolation from the warmer experiments of
      Merlivat and Nief [Merlivat L, Nief G (1967) Tellus 19:122-127]. Nonequilibrium
      kinetic effects that should alter preferential partitioning have also not been
      well characterized experimentally. We present here direct measurements of HDO/H2O
      equilibrium fractionation between vapor and ice ([Formula: see text]) at cirrus
      relevant temperatures, using in situ spectroscopic measurements of the evolving
      isotopic composition of water vapor during cirrus formation experiments in a
      cloud chamber. We rule out the recent proposed upward modification of [Formula:
      see text], and find values slightly lower than Merlivat and Nief. These
      experiments also allow us to make a quantitative validation of the kinetic
      modification expected to occur in supersaturated conditions in the ice-vapor
      system. In a subset of diffusion-limited experiments, we show that kinetic
      isotope effects are indeed consistent with published models, including allowing
      for small surface effects. These results are fundamental for inferring processes
      on Earth and other planets from water isotopic measurements. They also
      demonstrate the utility of dynamic in situ experiments for studying fractionation
      in geochemical systems.

PMID- 28495969
TI  - Fold-change detection and scale invariance of cell-cell signaling in social
      amoeba.
AB  - Cell-cell signaling is subject to variability in the extracellular volume, cell
      number, and dilution that potentially increase uncertainty in the absolute
      concentrations of the extracellular signaling molecules. To direct cell
      aggregation, the social amoebae Dictyostelium discoideum collectively give rise
      to oscillations and waves of cyclic adenosine 3',5'-monophosphate (cAMP) under a
      wide range of cell density. To date, the systems-level mechanism underlying the
      robustness is unclear. By using quantitative live-cell imaging, here we show that
      the magnitude of the cAMP relay response of individual cells is determined by
      fold change in the extracellular cAMP concentrations. The range of cell density
      and exogenous cAMP concentrations that support oscillations at the population
      level agrees well with conditions that support a large fold-change-dependent
      response at the single-cell level. Mathematical analysis suggests that invariance
      of the oscillations to density transformation is a natural outcome of combining
      secrete-and-sense systems with a fold-change detection mechanism.

PMID- 28495970
TI  - High-throughput biochemical profiling reveals sequence determinants of dCas9 off
      target binding and unbinding.
AB  - The bacterial adaptive immune system CRISPR-Cas9 has been appropriated as a
      versatile tool for editing genomes, controlling gene expression, and visualizing
      genetic loci. To analyze Cas9's ability to bind DNA rapidly and specifically, we
      generated multiple libraries of potential binding partners for measuring the
      kinetics of nuclease-dead Cas9 (dCas9) interactions. Using a massively parallel
      method to quantify protein-DNA interactions on a high-throughput sequencing flow
      cell, we comprehensively assess the effects of combinatorial mismatches between
      guide RNA (gRNA) and target nucleotides, both in the seed and in more distal
      nucleotides, plus disruption of the protospacer adjacent motif (PAM). We report
      two consequences of PAM-distal mismatches: reversal of dCas9 binding at long time
      scales, and synergistic changes in association kinetics when other gRNA-target
      mismatches are present. Together, these observations support a model for Cas9
      specificity wherein gRNA-DNA mismatches at PAM-distal bases modulate different
      biophysical parameters that determine association and dissociation rates. The
      methods we present decouple aspects of kinetic and thermodynamic properties of
      the Cas9-DNA interaction and broaden the toolkit for investigating off-target
      binding behavior.

PMID- 28495971
TI  - Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction
      Kinetics in Mice.
AB  - Animals detect odorous chemicals through specialized olfactory sensory neurons
      (OSNs) that transduce odorants into neural electrical signals. We identified a
      novel and evolutionarily conserved protein, cilia- and flagella-associated
      protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In
      the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory
      transduction occurs. Bioinformatic analysis suggests that a large portion of
      CFAP69 can form Armadillo-type alpha-helical repeats, which may mediate protein
      protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics
      in both the on and off phases of electrophysiological responses at both the
      neuronal ensemble level as observed by electroolfactogram and the single-cell
      level as observed by single-cell suction pipette recordings. In single-cell
      analysis, OSNs lacking CFAP69 showed faster response integration and were able to
      fire APs more faithfully to repeated odor stimuli. Furthermore, both male and
      female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated
      performance in a buried food pellet test when a background of the same odor to
      the food pellet was present even though they should have better temporal
      resolution of coding olfactory stimulation at the peripheral. Therefore, the role
      of CFAP69 in the olfactory system seems to be to allow the olfactory transduction
      machinery to work at a precisely regulated range of response kinetics for robust
      olfactory behavior.SIGNIFICANCE STATEMENT Sensory receptor cells are generally
      thought to evolve to respond to sensory cues as fast as they can. This idea is
      consistent with mutational analyses in various sensory systems, where mutations
      of sensory receptor cells often resulted in reduced response size and slowed
      response kinetics. Contrary to this idea, we have found that there is a kinetic
      "damper" present in the olfactory transduction cascade of the mouse that slows
      down the response kinetics and, by doing so, it reduces the peripheral temporal
      resolution in coding odor stimuli and allows for robust olfactory behavior. This
      study should trigger a rethinking of the significance of the intrinsic speed of
      sensory transduction and the pattern of the peripheral coding of sensory stimuli.

PMID- 28495972
TI  - Multiple Transient Signals in Human Visual Cortex Associated with an Elementary
      Decision.
AB  - The cerebral cortex continuously undergoes changes in its state, which are
      manifested in transient modulations of the cortical power spectrum. Cortical
      state changes also occur at full wakefulness and during rapid cognitive acts,
      such as perceptual decisions. Previous studies found a global modulation of beta
      band (12-30 Hz) activity in human and monkey visual cortex during an elementary
      visual decision: reporting the appearance or disappearance of salient visual
      targets surrounded by a distractor. The previous studies disentangled neither the
      motor action associated with behavioral report nor other secondary processes,
      such as arousal, from perceptual decision processing per se. Here, we used
      magnetoencephalography in humans to pinpoint the factors underlying the beta-band
      modulation. We found that disappearances of a salient target were associated with
      beta-band suppression, and target reappearances with beta-band enhancement. This
      was true for both overt behavioral reports (immediate button presses) and silent
      counting of the perceptual events. This finding indicates that the beta-band
      modulation was unrelated to the execution of the motor act associated with a
      behavioral report of the perceptual decision. Further, changes in pupil-linked
      arousal, fixational eye movements, or gamma-band responses were not necessary for
      the beta-band modulation. Together, our results suggest that the beta-band
      modulation was a top-down signal associated with the process of converting graded
      perceptual signals into a categorical format underlying flexible behavior. This
      signal may have been fed back from brain regions involved in decision processing
      to visual cortex, thus enforcing a "decision-consistent" cortical
      state.SIGNIFICANCE STATEMENT Elementary visual decisions are associated with a
      rapid state change in visual cortex, indexed by a modulation of neural activity
      in the beta-frequency range. Such decisions are also followed by other events
      that might affect the state of visual cortex, including the motor command
      associated with the report of the decision, an increase in pupil-linked arousal,
      fixational eye movements, and fluctuations in bottom-up sensory processing. Here,
      we ruled out the necessity of these events for the beta-band modulation of visual
      cortex. We propose that the modulation reflects a decision-related state change,
      which is induced by the conversion of graded perceptual signals into a
      categorical format underlying behavior. The resulting decision signal may be fed
      back to visual cortex.

PMID- 28495973
TI  - Contrasting the Role of xCT and GLT-1 Upregulation in the Ability of Ceftriaxone
      to Attenuate the Cue-Induced Reinstatement of Cocaine Seeking and Normalize AMPA
      Receptor Subunit Expression.
AB  - Long-term treatment with ceftriaxone attenuates the reinstatement of cocaine
      seeking while increasing the function of the glutamate transporter 1 (GLT-1) and
      system xC- (Sxc) in the nucleus accumbens core (NAc). Sxc contributes the
      majority of nonsynaptic extracellular glutamate in the NAc, while GLT-1 is
      responsible for the majority of glutamate uptake. Here we used antisense to
      decrease the expression of GLT-1 and xCT (a catalytic subunit of Sxc) to
      determine the relative importance of both proteins in mediating the ability of
      ceftriaxone to prevent cue-induced reinstatement of cocaine seeking and normalize
      glutamatergic proteins in the NAc of rats. Intra-NAc xCT knockdown prevented
      ceftriaxone from attenuating reinstatement and from upregulating GLT-1 and
      resulted in increased surface expression of AMPA receptor subunits GluA1 and
      GluA2. Intra-NAc GLT-1 knockdown also prevented ceftriaxone from attenuating
      reinstatement and from upregulating xCT expression, without affecting GluA1 and
      GluA2 expression. In the absence of cocaine or ceftriaxone treatment, xCT
      knockdown in the NAc increased the expression of both GluA1 and GluA2 without
      affecting GLT-1 expression while GLT-1 knockdown had no effect. PCR and
      immunoprecipitation of GLT-1 revealed that ceftriaxone does not upregulate GLT-1
      and xCT through a transcriptional mechanism, and their coregulation by
      ceftriaxone is not mediated by physical interaction. These data support important
      and distinct roles for xCT and GLT-1 in the actions of ceftriaxone and add to a
      body of literature finding evidence for coregulation of these transporters. Our
      results also point to xCT expression and subsequent basal glutamate levels as
      being a key mediator of AMPA receptor expression in the NAc.SIGNIFICANCE
      STATEMENT Ceftriaxone attenuates the reinstatement of cocaine, alcohol, and
      heroin seeking. The mechanism of action of this behavioral effect has been
      attributed to glutamate transporter 1 (GLT-1) and xCT (a catalytic subunit of
      Sxc)/Sxc upregulation in the nucleus accumbens core. Here we used an antisense
      strategy to knock down GLT-1 or xCT in the nucleus accumbens core and examined
      the behavioral and molecular consequences. While upregulation of both xCT and GLT
      1 are essential to the ability of ceftriaxone to attenuate cue-induced
      reinstatement of cocaine seeking, each protein uniquely affects the expression of
      other glutamate receptor and transporter proteins. We also report that reducing
      basal glutamate levels through the manipulation of xCT expression increases the
      surface expression of AMPA receptor subunits, providing insight to the mechanism
      by which cocaine alters AMPA surface expression.

PMID- 28495974
TI  - Long-Term Depression of Intrinsic Excitability Accompanied by Synaptic Depression
      in Cerebellar Purkinje Cells.
AB  - Long-term depression (LTD) at the parallel fiber (PF)-to-cerebellar Purkinje cell
      (PC) synapse is implicated in the output of PCs, the sole output of the
      cerebellar cortex. In addition to synaptic plasticity, intrinsic excitability is
      also one of the components that determines PC output. Although long-term
      potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to
      be investigated how PF-PC LTD modifies intrinsic excitability of PCs. Here, we
      show that pairing of the PF and climbing fiber (CF) for PF-PC LTD induction
      evokes LTD-IE in cerebellar PCs from male C57BL/6 mice. Interestingly, this
      intrinsic plasticity showed different kinetics from synaptic plasticity, but both
      forms of plasticity share Ca2+ signaling and protein kinase C pathway as their
      underlying mechanism. Although small-conductance Ca2+-activated K+ channels play
      important roles in LTP-IE, no direct implication has been found. After PF-PC LTD
      induction, neither the temporal summation of dendritic EPSP nor the power of
      spike frequency adaptation is changed, indicating that cerebellar LTD executes
      the information processing in a quantitative way without quality changes of
      synaptic integration and generation of output signals. Our results suggest that
      LTD-IE may have a synergistic effect with synaptic depression on the total net
      output of neurons by amplifying the modification of PF synaptic
      transmission.SIGNIFICANCE STATEMENT Although the output of Purkinje cells (PCs)
      is a critical component of cerebellum-dependent learning and memory, the changes
      of PC excitability when synaptic LTD occurs are unclear. Here, we show that the
      induction of PF-PC LTD evokes LTD-IE in PCs. Our observation complements previous
      intrinsic plasticity phenomenon of long-term potentiation of intrinsic
      excitability (LTP-IE), providing evidence for the idea that intrinsic plasticity
      has bidirectionality as synaptic plasticity. LTD-IE occurs together with synaptic
      LTD and both phenomena are dependent on the Ca2+ signaling pathway. Furthermore,
      our findings raise the prospect that this synaptic and intrinsic plasticity acts
      synergistically in PCs to modify neuronal activity in the same direction when
      learning occurs.

PMID- 28495979
TI  - Meet the First Authors.

PMID- 28495976
TI  - Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt
      Seeking.
AB  - Salt appetite, in which animals can immediately seek out salt when under a novel
      state of sodium deprivation, is a classic example of how homeostatic systems
      interface with learned associations to produce an on-the-fly updating of
      motivated behavior. Neural activity in the ventral pallidum (VP) has been shown
      to encode changes in the value of salt under such conditions, both the value of
      salt itself (Tindell et al., 2006) and the motivational value of its predictive
      cues (Tindell et al., 2009; Robinson and Berridge, 2013). However, it is not
      known whether the VP is necessary for salt appetite in terms of seeking out salt
      or consuming salt following sodium depletion. Here, we used a conditioned place
      preference procedure to investigate the effects of optogenetically inhibiting the
      VP on context-driven salt seeking and the consumption of salt following
      deprivation. Male rats learned to associate one context with sucrose and another
      context with less-desirable salt. Following sodium depletion, and in the absence
      of either sucrose or salt, we found that inhibiting the VP selectively reduced
      the elevation in time spent in the salt-paired context. VP inhibition had minimal
      effects on the consumption of salt once it was made available. To our knowledge,
      this is the first evidence that the VP or any brain region is necessary for the
      ability to use contextual cues to guide salt seeking. These results highlight a
      dissociation between deficit-driven reward seeking and reward consumption to
      replenish those deficits, with the former process being particularly sensitive to
      on-line VP activity.SIGNIFICANCE STATEMENT Salt appetite, in which rats will
      immediately seek out a once-undesirable concentrated salt solution after being
      depleted of bodily sodium despite never having tasted salt as a positive reward,
      is a phenomenon showing how animals can update their motivational goals without
      any new learning or conditioning. This salt-seeking behavior is also observed
      when the animal is presented with salt-paired cues. The neural circuitry
      necessary for context-driven salt-seeking behavior is unknown. We used a novel
      conditioned place preference procedure to show that optogenetic inhibition of the
      ventral pallidum (VP), a region known for processing reward, impairs context
      driven salt seeking and has minimal effects on the consumption of salt itself
      following sodium depletion. These results highlight the importance of the VP in
      context-driven reward-seeking behavior.

PMID- 28495975
TI  - Short-Term Depression of Sprouted Mossy Fiber Synapses from Adult-Born Granule
      Cells.
AB  - Epileptic seizures potently modulate hippocampal adult neurogenesis, and adult
      born dentate granule cells contribute to the pathologic retrograde sprouting of
      mossy fiber axons, both hallmarks of temporal lobe epilepsy. The characteristics
      of these sprouted synapses, however, have been largely unexplored, and the
      specific contribution of adult-born granule cells to functional mossy fiber
      sprouting is unknown, primarily due to technical barriers in isolating sprouted
      mossy fiber synapses for analysis. Here, we used DcxCreERT2 transgenic mice to
      permanently pulse-label age-defined cohorts of granule cells born either before
      or after pilocarpine-induced status epilepticus (SE). Using optogenetics, we
      demonstrate that adult-born granule cells born before SE form functional
      recurrent monosynaptic excitatory connections with other granule cells.
      Surprisingly, however, although healthy mossy fiber synapses in CA3 are well
      characterized "detonator" synapses that potently drive postsynaptic cell firing
      through their profound frequency-dependent facilitation, sprouted mossy fiber
      synapses from adult-born cells exhibited profound frequency-dependent depression,
      despite possessing some of the morphological hallmarks of mossy fiber terminals.
      Mature granule cells also contributed to functional mossy fiber sprouting, but
      exhibited less synaptic depression. Interestingly, granule cells born shortly
      after SE did not form functional excitatory synapses, despite robust sprouting.
      Our results suggest that, although sprouted mossy fibers form recurrent
      excitatory circuits with some of the morphological characteristics of typical
      mossy fiber terminals, the functional characteristics of sprouted synapses would
      limit the contribution of adult-born granule cells to hippocampal
      hyperexcitability in the epileptic hippocampus.SIGNIFICANCE STATEMENT In the
      hippocampal dentate gyrus, seizures drive retrograde sprouting of granule cell
      mossy fiber axons. We directly activated sprouted mossy fiber synapses from adult
      born granule cells to study their synaptic properties. We reveal that sprouted
      synapses from adult-born granule cells have a diminished ability to sustain
      recurrent excitation in the epileptic hippocampus, which raises questions about
      the role of sprouting and adult neurogenesis in sustaining seizure-like activity.

PMID- 28495977
TI  - Modelling the implications of reducing smoking prevalence: the public health and
      economic benefits of achieving a 'tobacco-free' UK.
AB  - INTRODUCTION: Smoking is still the most preventable cause of cancer, and a
      leading cause of premature mortality and health inequalities in the UK. This
      study modelled the health and economic impacts of achieving a 'tobacco-free'
      ambition (TFA) where, by 2035, less than 5% of the population smoke tobacco
      across all socioeconomic groups. METHODS: A non-linear multivariate regression
      model was fitted to cross-sectional smoking data to create projections to 2035.
      These projections were used to predict the future incidence and costs of 17
      smoking-related diseases using a microsimulation approach. The health and
      economic impacts of achieving a TFA were evaluated against a predicted baseline
      scenario, where current smoking trends continue. RESULTS: If trends continue, the
      prevalence of smoking in the UK was projected to be 10% by 2035-well above a TFA.
      If this ambition were achieved by 2035, it could mean 97 300 +/- 5 300 new cases
      of smoking-related diseases are avoided by 2035 (tobacco-related cancers: 35
      900+/- 4 100; chronic obstructive pulmonary disease: 29 000 +/- 2 700; stroke: 24
      900 +/- 2 700; coronary heart disease: 7600 +/- 2 700), including around 12 350
      diseases avoided in 2035 alone. The consequence of this health improvement is
      predicted to avoid L67 +/- 8 million in direct National Health Service and social
      care costs, and L548 million in non-health costs, in 2035 alone. CONCLUSION:
      These findings strengthen the case to set bold targets on long-term declines in
      smoking prevalence to achieve a tobacco 'endgame'. Results demonstrate the health
      and economic benefits that meeting a TFA can achieve over just 20 years.
      Effective ambitions and policy interventions are needed to reduce the disease and
      economic burden of smoking.

PMID- 28495980
TI  - Get Your Cell K.O. in the First Round.

PMID- 28495981
TI  - Pacing Discovery: G-Protein beta Subunit Mutations in Sinus Node Dysfunction.

PMID- 28495982
TI  - A New Role of Mister (MR) T in Hypertension: Mineralocorticoid Receptor, Immune
      System, and Hypertension.

PMID- 28495983
TI  - Immunomodulation Is the Key to Cardiac Repair.

PMID- 28495984
TI  - "Pound-Years": Effects on the Heart of Long-Term Exposure to Obesity.

PMID- 28495985
TI  - Oliver Smithies, DPhil: 1925-2017.

PMID- 28495986
TI  - PCSK9 Inhibition to Reduce Cardiovascular Risk: Tempering Expectations.

PMID- 28495987
TI  - A Multidisciplinary and Multicultural Adventure: From Materials Engineering to
      Cardiovascular Science.

PMID- 28495988
TI  - Rong Tian: Finding What Feeds the Heart.

PMID- 28495990
TI  - The Texas Heart Institute: Part 2-Working Toward the Next Breakthrough in
      Cardiovascular Medicine.

PMID- 28495989
TI  - The Texas Heart Institute: Part 1-An Historical Perspective.

PMID- 28495991
TI  - It's 10 pm; Do You Know Where Your Data Are? Data Provenance, Curation, and
      Storage.

PMID- 28495992
TI  - Scientific Discovery, Contextual Factors, and Cardiometabolic Health Research:
      Back to the Future.

PMID- 28495993
TI  - Safe and Effective Cardiac Regenerative Therapy With Human-Induced Pluripotent
      Stem Cells: How Should We Prepare Pure Cardiac Myocytes?

PMID- 28495994
TI  - Methodological Guidelines to Study Extracellular Vesicles.
AB  - Owing to the relationship between extracellular vesicles (EVs) and physiological
      and pathological conditions, the interest in EVs is exponentially growing. EVs
      hold high hopes for novel diagnostic and translational discoveries. This review
      provides an expert-based update of recent advances in the methods to study EVs
      and summarizes currently accepted considerations and recommendations from sample
      collection to isolation, detection, and characterization of EVs. Common
      misconceptions and methodological pitfalls are highlighted. Although EVs are
      found in all body fluids, in this review, we will focus on EVs from human blood,
      not only our most complex but also the most interesting body fluid for
      cardiovascular research.

PMID- 28495995
TI  - Extracellular Vesicles in Cardiovascular Disease: Potential Applications in
      Diagnosis, Prognosis, and Epidemiology.
AB  - Extracellular vesicles originate from diverse subcellular compartments and are
      released in the extracellular space. By transferring their cargoes into target
      cells and tissues, they now emerge as novel regulators of intercellular
      communication between adjacent and remote cells. Because vesicle composition and
      biological content are specific signatures of cellular activation and injury,
      their potential as diagnostic and prognostic biomarkers has raised significant
      interest in cardiovascular diseases. Characterization of circulating vesicles- or
      nonvesicles-bound nucleic acids represents a valuable tool for diagnosing and
      monitoring cardiovascular diseases, recently referred to as a liquid biopsy.
      Circulating extracellular vesicles offer a noninvasive and almost continuous
      access to circulating information on the disease state in epidemiological
      investigations. Finally, genetic engineering and cell-specific application of
      extracellular vesicles could display a novel therapeutic option for the treatment
      of cardiovascular diseases. In this review, we summarize the current knowledge
      about extracellular vesicles as diagnostic and prognostic biomarkers, as well as
      their potential applications for longitudinal epidemiological studies in
      cardiovascular diseases.

PMID- 28495997
TI  - Extracellular Vesicles in Metabolic Syndrome.
AB  - Metabolic syndrome defines a cluster of interrelated risk factors for
      cardiovascular disease and diabetes mellitus. These factors include metabolic
      abnormalities, such as hyperglycemia, elevated triglyceride levels, low high
      density lipoprotein cholesterol levels, high blood pressure, and obesity, mainly
      central adiposity. In this context, extracellular vesicles (EVs) may represent
      novel effectors that might help to elucidate disease-specific pathways in
      metabolic disease. Indeed, EVs (a terminology that encompasses microparticles,
      exosomes, and apoptotic bodies) are emerging as a novel mean of cell-to-cell
      communication in physiology and pathology because they represent a new way to
      convey fundamental information between cells. These microstructures contain
      proteins, lipids, and genetic information able to modify the phenotype and
      function of the target cells. EVs carry specific markers of the cell of origin
      that make possible monitoring their fluctuations in the circulation as potential
      biomarkers inasmuch their circulating levels are increased in metabolic syndrome
      patients. Because of the mixed components of EVs, the content or the number of
      EVs derived from distinct cells of origin, the mode of cell stimulation, and the
      ensuing mechanisms for their production, it is difficult to attribute specific
      functions as drivers or biomarkers of diseases. This review reports recent data
      of EVs from different origins, including endothelial, smooth muscle cells,
      macrophages, hepatocytes, adipocytes, skeletal muscle, and finally, those from
      microbiota as bioeffectors of message, leading to metabolic syndrome. Depicting
      the complexity of the mechanisms involved in their functions reinforce the
      hypothesis that EVs are valid biomarkers, and they represent targets that can be
      harnessed for innovative therapeutic approaches.

PMID- 28495998
TI  - Correction to: Experimental, Systems, and Computational Approaches to
      Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor
      Cell-Derived Exosomes From Pediatric Patients.

PMID- 28495996
TI  - Extracellular Vesicles in Angiogenesis.
AB  - During the past decade, extracellular vesicles (EVs), which include apoptotic
      bodies, microvesicles, and exosomes, have emerged as important players in cell-to
      cell communication in normal physiology and pathological conditions. EVs
      encapsulate and convey various bioactive molecules that are further transmitted
      to neighboring or more distant cells, where they induce various signaling
      cascades. The message delivered to the target cells is dependent on EV
      composition, which, in turn, is determined by the cell of origin and the
      surrounding microenvironment during EV biogenesis. Among their multifaceted role
      in the modulation of biological responses, the involvement of EVs in vascular
      development, growth, and maturation has been widely documented and their
      potential therapeutic application in regenerative medicine or angiogenesis
      related diseases is drawing increasing interest. EVs derived from various cell
      types have the potential to deliver complex information to endothelial cells and
      to induce either pro- or antiangiogenic signaling. As dynamic systems, in
      response to changes in the microenvironment, EVs adapt their cargo composition to
      fine-tune the process of blood vessel formation. This article reviews the current
      knowledge on the role of microvesicles and exosomes from various cellular origins
      in angiogenesis, with a particular emphasis on the underlying mechanisms, and
      discusses the main challenges and prerequisites for their therapeutic
      applications.

PMID- 28495999
TI  - beta-Arrestin-Mediated Regulation of the Human Ether-a-go-go-Related Gene
      Potassium Channel.
AB  - The rapidly activating delayed rectifier K+ channel (IKr) is encoded by the human
      ether-a-go-go-related gene (hERG), which is important for the repolarization of
      the cardiac action potential. Mutations in hERG or drugs can impair the function
      or decrease the expression level of hERG channels, leading to long QT syndrome.
      Thus, it is important to understand hERG channel trafficking and its regulation.
      For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast
      array of cellular processes, represent a useful route. The development of
      designer GPCRs known as designer receptors exclusively activated by designer
      drugs (DREADDs) has made it possible to dissect specific GPCR signaling pathways
      in various cellular systems. In the present study, by expressing an arrestin
      biased M3 muscarinic receptor-based DREADD (M3D-arr) in stable hERG-expressing
      human embryonic kidney (HEK) cells, we demonstrate that beta-arrestin signaling
      plays a role in hERG regulation. By exclusively activating M3D-arr using the
      otherwise inert compound, clozapine-N-oxide, we found that M3D-arr activation
      increased mature hERG expression and current. Within this paradigm, M3D-arr
      recruited beta-arrestin-1 to the plasma membrane, and promoted phosphoinositide 3
      kinase-dependent activation of protein kinase B (Akt). The activated Akt acted
      through phosphatidylinositol 3-phosphate 5-kinase and Rab11 to facilitate hERG
      recycling to the plasma membrane. Potential beta-arrestin signaling-mediated
      increases in hERG and IKr were also observed in hERG-HEK cells as well as in
      neonatal rat ventricular myocytes treated with the muscarinic agonist carbachol.
      These findings provide novel insight into hERG trafficking and regulation.

PMID- 28496000
TI  - Stratification according to recursive partitioning analysis predicts outcome in
      newly diagnosed glioblastomas.
AB  - Glioblastoma accounts for more than half of diffuse gliomas. The prognosis of
      patients with glioblastoma remains poor despite comprehensive and intensive
      treatments. Furthermore, the clinical significance of molecular parameters and
      routinely available clinical variables for the prognosis prediction of
      glioblastomas remains limited. The authors describe a novel model may help in
      prognosis prediction and clinical management of glioblastoma patients. We
      performed a recursive partitioning analysis to generate three independent
      prognostic classes of 103 glioblastomas patients from TCGA dataset. Class I (MGMT
      promoter methylated, age <58), class II (MGMT promoter methylation, age >=58;
      MGMT promoter unmethylation, age <54, KPS >=70; MGMT promoter unmethylation, age
      >59, KPS >=70), class III (MGMT promoter unmethylation, age 54-58, KPS >=70; MGMT
      promoter unmethylation, KPS <70). Age, KPS and MGMT promoter methylation were the
      most significant prognostic factors for overall survival. The results were
      validated in CGGA dataset.This was the first study to combine various molecular
      parameters and clinical factors into recursive partitioning analysis to predict
      the prognosis of patients with glioblastomas. We included MGMT promoter
      methylation in our study, which could give better suggestion to patients for
      their chemotherapy. This clinical study will serve as the backbone for the future
      incorporation of molecular prognostic markers currently in development. Thus, our
      recursive partitioning analysis model for glioblastomas may aid in clinical
      prognosis evaluation.

PMID- 28496001
TI  - DDX11-AS1 as potential therapy targets for human hepatocellular carcinoma.
AB  - Hepatocellular Carcinoma (HCC) is one of the most fatal cancers, whose incidence
      and death rates are still rising. Here, we report the identification of long non
      coding RNAs (IncRNAs) that associated with HCC progression and metabolism based
      on the systematically analysis of large scale RNA-seq data from HCC patients. We
      identified seven lncRNAs with high confidence which were highly related with
      prognostic of HCC. Of note, three of them had quite different expression patterns
      between the control samples and the patients, and their critical roles in cancer
      progression were validated. We proposed that DDX11-AS1 play important role during
      HCC oncogenesis and may serve as potential therapy target for HCC.

PMID- 28496002
TI  - Risk of cancer in patients with heart failure who use digoxin: a 10-year follow
      up study and cell-based verification.
AB  - Heart failure (HF) is the leading cause of death in the world and digoxin remains
      one of the oldest therapies for HF. However, its safety and efficacy have been
      controversial since its initial use and there is uncertainty about its long-term
      efficacy and safety. Recently, the repositioning of cardiac glycosides is to
      function in anti-tumor activity via multiple working pathways. It is interesting
      to compare the potential effects of digoxin in clinical patients and cell lines.
      First, we analyze patient information retrieved from the National Health
      Insurance Research database of Taiwan between January 1, 2000 and December 31,
      2000. This retrospective study included a study cohort (1,219 patients) and a
      comparison cohort. Our analytical data suggested that patients taking digoxin are
      at an increased risk of cancers, including breast, liver, and lung cancers,
      during the 10-year follow-up period. In contrast to the anti-tumor function of
      digoxin, we further examined the potential pathway of digoxin via the cell-based
      strategy using several breast cancer cell lines, including MCF-7, BT-474, MAD-MB
      231, and ZR-75-1. Digoxin consistently exerted its cytotoxicity to these four
      cell lines with various range of concentration. However, the proliferation of ZR
      75-1 cells was the only cell lines induced by digoxin and the others were
      dramatically suppressed by digoxin. The responsiveness of SRSF3 to digoxin might
      be involved with cell-type differences. In summary, we combined a cohort study
      for digoxin treatment for HF patients with a cell-based strategy that addresses
      the translation issue, which revealed the complexity of personalized medicine.

PMID- 28496003
TI  - Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and
      autophagy and modulating key metabolic pathways.
AB  - Peiminine, a compound extracted from the bulbs of Fritillaria thunbergii and
      traditionally used as a medication in China and other Asian countries, was
      reported to inhibit colorectal cancer cell proliferation and tumor growth by
      inducing autophagic cell death. However, its mechanism of anticancer action is
      not well understood, especially at the metabolic level, which was thought to
      primarily account for peiminine's efficacy against cancer. Using an established
      metabolomic profiling platform combining ultra-performance liquid
      chromatography/tandem mass spectrometry with gas chromatography/mass
      spectrometry, we identified metabolic alterations in colorectal cancer cell line
      HCT-116 after peiminine treatment. Among the identified 236 metabolites, the
      levels of 57 of them were significantly (p < 0.05) different between peiminine
      treated and -untreated cells in which 45 metabolites were increased and the other
      12 metabolites were decreased. Several of the affected metabolites, including
      glucose, glutamine, oleate (18:1n9), and lignocerate (24:0), may be involved in
      regulation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin
      (mTOR) pathway and in the oxidative stress response upon peiminine exposure.
      Peiminine predominantly modulated the pathways responsible for metabolism of
      amino acids, carbohydrates, and lipids. Collectively, these results provide new
      insights into the mechanisms by which peiminine modulates metabolic pathways to
      inhibit colorectal cancer cell growth, supporting further exploration of
      peiminine as a potential new strategy for treating colorectal cancer.

PMID- 28496004
TI  - The lymph node ratio as an independent prognostic factor for node-positive triple
      negative breast cancer.
AB  - BACKGROUND: We aimed to evaluate the prognostic value of the lymph node ratio
      (LNR) in patients with axillary lymph node-positive triple-negative breast cancer
      (TNBC). METHODS: The prognostic efficacy was investigated in the first cohort
      from the Surveillance, Epidemiology, and End Results (SEER) dataset (n=4114) and
      was further validated in an independent cohort from Fudan University Shanghai
      Cancer Center (n=417). Patients were classified into low-, medium- and high-risk
      LNR groups. RESULTS: Multivariate analysis revealed that the LNR was an
      independent predictor of overall survival (hazard ratio (HR) for high-risk LNR:
      3.24; 95% confidence interval (CI): 2.56 to 4.09) and breast cancer-specific
      survival (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER
      population and also for disease-free survival (HR for high-risk LNR: 4.29; 95%
      CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that
      patient classification according to the LNR could discriminate among groups of
      patients with different survival rates based on pathological nodal (pN) staging.
      CONCLUSION: The LNR shows potential for use as an additional prognostic factor
      for TNBC patients with positive lymph node involvement. Considering the
      heterogeneity of TNBC, use of the LNR might allow for optimization of the pN
      staging system and should be considered when making treatment decisions.

PMID- 28496005
TI  - Circulating plasma microRNAs as potential markers to identify EGFR mutation
      status and to monitor epidermal growth factor receptor-tyrosine kinase inhibitor
      treatment in patients with advanced non-small cell lung cancer.
AB  - We aimed to identify a panel of circulating plasma microRNAs that can predict
      EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase
      inhibitor treatment in patients with non-small cell lung cancer. Microarrays were
      performed for the preliminary screening of dysregulated microRNAs in 9 EGFR
      mutation-positive patients versus healthy controls. MiR-107 was upregulated and
      miR-195 was downregulated in the exon 19 deletion versus wild-type group. The
      areas under the receiver operating characteristic curves for miR-107, miR-195,
      and a panel of these 2 microRNAs were 0.72, 0.75, and 0.74, with sensitivities
      and specificities of 64.7% and 76.6%, 71.8% and 69.1%, and 71.7% and 78.9%,
      respectively. MiR-122 was significantly upregulated in the p.L858R versus wild
      type group. An area under the receiver operative characteristic curve of 0.75
      suggests that miR-122 might be a specific biomarker for patients with the p.L858R
      mutation. In addition, dynamic changes in these 3 microRNAs were also found to
      correlate with responses to epidermal growth factor receptor-tyrosine kinase
      inhibitor treatment, indicating that circulating plasma microRNAs may represent
      potential biomarkers for monitoring epidermal growth factor receptor-tyrosine
      kinase inhibitor treatment. This study demonstrates the prospective application
      of circulating plasma microRNAs as potential non-invasive, convenient biomarkers
      for patients with EGFR-sensitive mutations.

PMID- 28496006
TI  - Gene expression signature of Gleason score is associated with prostate cancer
      outcomes in a radical prostatectomy cohort.
AB  - Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide.
      Gleason score (GS) is one of the best predictors of PCa aggressiveness, but
      additional tumor biomarkers may improve its prognostic accuracy. We developed a
      gene expression signature of GS to enhance the prediction of PCa outcomes.
      Elastic net was used to construct a gene expression signature by contrasting GS 8
      10 vs. <=6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed
      signature was then evaluated for its ability to predict recurrence and metastatic
      lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408;
      NRecurrence=109; NMLprogression=27). The expression signature included
      transcripts representing 49 genes. In the FH cohort, a 25% increase in the
      signature was associated with a hazard ratio (HR) of 1.51 (P=2.7*10-5) for
      recurrence. The signature's area under the curve (AUC) for predicting recurrence
      and ML progression was 0.68 and 0.76, respectively. Compared to a model with age
      at diagnosis, pathological stage and GS, the gene expression signature improved
      the AUC for recurrence (3%) and ML progression (6%). Higher levels of the
      signature were associated with increased expression of genes in cell cycle
      related pathways and decreased expression of genes in androgen response, estrogen
      response, oxidative phosphorylation, and apoptosis. This gene expression
      signature based on GS may improve the prediction of recurrence as well as ML
      progression in PCa patients after radical prostatectomy.

PMID- 28496007
TI  - Association between tea consumption and risk of cognitive disorders: A dose
      response meta-analysis of observational studies.
AB  - BACKGROUND: The epidemiological evidence for a dose-response relationship between
      tea consumption and risk of cognitive disorders is sparse. The aim of the study
      was to summarize the evidence for the association of tea consumption with risk of
      cognitive disorders and assess the dose-response relationship. METHODS: We
      searched electronic databases of Pubmed, Embase, and Cochrane Library (from 1965
      to Jan 19, 2017) for eligible studies that published in the international
      journals. A random-effects model was used to pool the most adjusted odds ratios
      (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: Seventeen
      studies involving 48,435 participants were included in our study. The meta
      analysis showed that a higher tea consumption was associated with a significant
      reduction in the risk of cognitive disorders (OR=0.73, 95% CI: 0.65-0.82). When
      considering the specific types of tea consumption, the significantly inverse
      association is only found in green tea consumption (OR=0.64, 95% CI: 0.53-0.77)
      but not in black/oolong tea consumption (OR=0.75, 95% CI: 0.55-1.01). Dose
      response meta-analysis indicated that tea consumption is linearly associated with
      a reduced risk of cognitive disorders. An increment of 100 ml/day, 300 ml/day,
      and 500 ml/day of tea consumption was associated with a 6% (OR=0.94, 95% CI: 0.92
      0.96), 19% (OR=0.81, 95% CI: 0.74-0.88), and 29% (OR=0.71, 95% CI: 0.62-0.82)
      lower risk of cognitive disorders. CONCLUSIONS: Tea consumption is inversely and
      linearly related to the risk of cognitive disorders. More studies are needed to
      further confirm our findings.

PMID- 28496009
TI  - Dynamic changes in clonal cytogenetic architecture during progression of chronic
      lymphocytic leukemia in patients and patient-derived murine xenografts.
AB  - Subclonal heterogeneity and clonal selection influences disease progression in
      chronic lymphocytic leukemia (CLL). It is therefore important that therapeutic
      decisions are made based on an understanding of the CLL clonal architecture and
      its dynamics in individual patients. Identification of cytogenetic abnormalities
      by FISH remains the cornerstone of contemporary clinical practice and provides a
      simple means for prognostic stratification. Here, we demonstrate that multiplexed
      FISH can enhance recognition of CLL subclonal repertoire and its dynamics during
      disease progression, both in patients and CLL patient-derived xenografts (PDX).
      We applied a combination of patient-specific FISH probes to 24 CLL cases before
      treatment and at relapse, and determined putative ancestral relationships between
      subpopulations with different cytogenetic features. We subsequently established 7
      CLL PDX models in NOD/Shi-SCID/IL-2Rgammactm1sug/Jic (NOG) mice. Application of
      multiplexed-FISH to these models demonstrated that all of the identified
      cytogenetic subpopulations had leukemia propagating activity and that changes in
      their representation during disease progression could be spontaneous, accelerated
      by treatment or treatment-induced. We conclude that multiplexed-FISH in
      combination with PDX models have the potential to distinguish between spontaneous
      and treatment-induced clonal selection, and therefore provide a valuable tool for
      the pre-clinical evaluation of novel therapies.

PMID- 28496010
TI  - Characteristics of delayed intracerebral hemorrhage after ventriculoperitoneal
      shunt insertion.
AB  - BACKGROUND: Delayed intracerebral hemorrhage after ventriculoperitoneal (VP)
      shunt insertion is rare and has not been well investigated previously. Its
      characteristics is still unknown. OBJECTIVE: We reported 12 patients with delayed
      intracerebral hemorrhage after VP shunt to investigate the potential risk factors
      and the outcome. RESULTS: 12 patients (1.59%) of all the 754 hydrocephalus had
      delayed intracerebral hemorrhage after VP shunt insertion. 4 patients were women
      and 8 patients were men, ranging in age from 50 to 76 years. The delayed cerebral
      hemorrhage from day 3 to day 7 post operation was diagnosed by repeated CT. The
      delayed intracerebral hemorrhage was significantly related to age, prior
      craniotomy operation history and manipulation of valve system (3-7 days). Neither
      gender sexuality nor potential risk factors for postoperative hemorrhage
      (including anticoagulation/antiplatelet status, liver disease, diabetes,
      hypertension), time of shunt attempt affected the happen of delayed intracerebral
      hemorrhage. MATERIALS AND METHODS: The clinical characteristics including sex,
      age, anticoagulation/antiplatelet status, liver disease, diabetes, hypertension,
      craniotomy operation history, manipulation of valve system and time of shunt
      attempt of 754 patients who were surgically treated of VP shunt at the first
      affiliated hospital of Soochow University between 2007 and 2013 were reviewed
      retrospectively. The potential risk factors of the delayed intracerebral
      hemorrhage were statistically analyzed. CONCLUSIONS: This study summarizes the
      presentation and outcome of a series of 12 patients with delayed intracerebral
      hemorrhage after VP shunt. Age >= 60 years, prior craniotomy operation and
      manipulation of the valve system are statistically significant to the delayed
      hematoma secondary to VP shunt.

PMID- 28496011
TI  - Polymer toxicity in neurodegeneration FENIB.

PMID- 28496012
TI  - Daytime behavior of Pteropus vampyrus in a natural habitat: the driver of viral
      transmission.
AB  - Flying foxes, the genus Pteropus, are considered viral reservoirs. Their colonial
      nature and long flight capability enhance their ability to spread viruses
      quickly. To understand how the viral transmission occurs between flying foxes and
      other animals, we investigated daytime behavior of the large flying fox (Pteropus
      vampyrus) in the Leuweung Sancang conservation area, Indonesia, by using
      instantaneous scan sampling and all-occurrence focal sampling. The data were
      obtained from 0700 to 1700 hr, during May 11-25, 2016. Almost half of the flying
      foxes (46.9 +/- 10.6% of all recorded bats) were awake and showed various levels
      of activity during daytime. The potential behaviors driving disease transmission,
      such as self-grooming, mating/courtship and aggression, peaked in the early
      morning. Males were more active and spent more time on sexual activities than
      females. There was no significant difference in time spent for negative social
      behaviors between sexes. Positive social behaviors, especially maternal cares,
      were performed only by females. Sexual activities and negative/positive social
      behaviors enable fluid exchange between bats and thus facilitate intraspecies
      transmission. Conflicts for living space between the flying foxes and the ebony
      leaf monkey (Trachypithecus auratus) were observed, and this caused daily
      roosting shifts of flying foxes. The ecological interactions between bats and
      other wildlife increase the risk of interspecies infection. This study provides
      the details of the flying fox's behavior and its interaction with other wildlife
      in South-East Asia that may help explain how pathogen spillover occurs in the
      wild.

PMID- 28496013
TI  - Enhancement of bactericidal effects of sodium hypochlorite in chiller water with
      food additive grade calcium hydroxide.
AB  - An alkaline agent, namely food additive grade calcium hydroxide (FdCa(OH)2) in
      solution at 0.17%, was evaluated for its bactericidal efficacies in chiller water
      with sodium hypochlorite (NaOCl) at a concentration of 200 ppm total residual
      chlorine. Without organic material presence, NaOCl could inactivate Salmonella
      Infantis and Escherichia coli within 5 sec, but in the presence of fetal bovine
      serum (FBS) at 0.5%, the bactericidal effects of NaOCl were diminished
      completely. FdCa(OH)2 solution required 3 min to inactivate bacteria with or
      without 5% FBS. When NaOCl and FdCa(OH)2 were mixed at the final concentration of
      200 ppm and 0.17%, respectively, the mixed solution could inactivate bacteria at
      acceptable level (103 reduction of bacterial titer) within 30 sec in the presence
      of 0.5% FBS. The mixed solution also inhibited cross-contamination with S.
      Infantis or E. coli on chicken meats. It was confirmed and elucidated that
      FdCa(OH)2 has a synergistic effect together with NaOCl for inactivating
      microorganisms.

PMID- 28496014
TI  - Prognostic Factors for In-Hospital and Long-Term Survival in Patients with Acute
      ST-Segment Elevation Myocardial Infarction after Percutaneous Coronary
      Intervention.
AB  - Acute ST segment elevation myocardial infarction (STEMI) is one of the causes of
      death and disability in patients with cardiovascular diseases. This study aimed
      to investigate the prognostic factors of in-hospital and long-term survival in
      patients with acute STEMI undergoing percutaneous coronary intervention (PCI).
      Patients with STEMI undergoing PCI were divided into the death group (n = 54) and
      the survival group (n = 306) based on the outcomes during hospitalization. The
      routine blood and biochemistry tests, Killip classes and global registry of acute
      coronary events (GRACE) risk score were detected. The 1-, 2- and 3-year survival
      rates after PCI was observed through a 3-year follow-up. The survival factors,
      survival rates and multivariate analyses were conducted using Logistic regression
      analysis, Kaplan-Meier survival analysis and Cox proportional hazards regression.
      The incidence of cardiogenic shock and anterior wall MI (AWMI), the serum levels
      of gamma-glutamyl endopeptidase (gamma-GGT) and creatine kinase isoenzyme MB (CK
      MB), Killip classes and GRACE risk score were higher in the death group, compared
      with the survival group. AWMI, cardiogenic shock, high serum levels of gamma-GGT
      and CK-MB, Killip class III-IV and high GRACE risk scores were associated with in
      hospital mortality. AWMI, cardiogenic shock, Killip class III-IV and high GRACE
      risk scores were correlated with a poor long-term survival. Our findings have
      demonstrated that AWMI, cardiogenic shock, high serum levels of gamma-GGT and CK
      MB, Killip class III-IV, and high GRACE risk scores are risk factors for in
      hospital and long-term prognosis of acute STEMI patients.

PMID- 28496015
TI  - Determining the Possible Etiology of Hospital-Acquired Pneumonia Using a Clone
      Library Analysis in Japan.
AB  - Obtaining precise etiological information regarding causative bacteria is
      important for the proper use of antimicrobials in hospital-acquired pneumonia
      (HAP), which is associated with a high rate of mortality. The aim of this study
      was to comparatively investigate the bacterial diversity in bronchoalveolar
      lavage fluid (BALF) in Japanese patients with HAP by the clone library method
      using the 16S rRNA gene. This study included Japanese patients with HAP who were
      treated at our hospital and referring hospitals. BALF specimens were obtained
      from pneumonia lesions identified on chest radiographs and/or computed
      tomography. Sputum specimens were also evaluated in patients with sputum
      production. Sixty-eight patients were ultimately enrolled. BALF cultivation
      revealed bacterial positivity in 53 of 68 (77.9%) patients, and Staphylococcus
      aureus (30.9%) was the most frequently isolated, followed by Pseudomonas
      aeruginosa (16.2%), and Escherichia coli (10.3%). In contrast, the clone library
      analysis identified the presence of some bacterial phenotype in 65 of 68 (95.6%)
      patients, and streptococci (16.2%), Corynebacterium species (11.8%), anaerobes
      (10.3%) were frequently detected as the predominant phylotypes. Both methods
      tended to detect S. aureus, Klebsiella pneumoniae, and E. coli in patients with
      late-onset pneumonia. In addition, the cases that phylotypes of S. aureus and P.
      aeruginosa were found to account for > 5% of the bacterial flora of each case
      were 42.9% and 72.7%, respectively. These results indicate that attention should
      be paid to the roles of gram-positive bacilli such as streptococci,
      Corynebacterium species and anaerobes, in addition to Gram-negative bacilli, in
      the pathogenesis of HAP.

PMID- 28496016
TI  - Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy
      Evaluation of the Efficacy by Patients Themselves.
AB  - Anticancer drug-induced stomatitis develops in 30% to 40% of cancer cases that
      undergo chemotherapy. However, medications for this condition are not
      commercially available in Japan. Upon obtaining approval of the ethics committee,
      a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash)
      was administered to one inpatient and four outpatients, who had developed
      stomatitis caused by cancer chemotherapy. Starting from 14 d after the
      administration of the rebamipide mouthwash, the patients scored a stomatitis
      survey on oral state, pain level, and diet and recorded the number of times they
      gargled, as well as any stomatitis observations, in a stomatitis diary. The total
      scores for the points for each of the three types of survey sections were
      classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score
      (SES). The SES became "0" in three out of the five patients within 14 d of
      treatment. No change in SES was found in one patient. In the remaining patients,
      SES became "0" once but increased again later. Using image analysis software
      (ImageJ), the area at which the stomatitis was observed was measured. When
      comparing SES and change in the area in patients who agreed to participate,
      gradual reductions in the extent of stomatitis was observed even during the
      period when SES did not change. Having patients fill in an observation chart was
      effective for grasping changes in symptoms in outpatients.

PMID- 28496017
TI  - Comparison of the Incidence of Complications and Secondary Surgical Interventions
      Necessary in Patients with Chronic Lower Limb Ischemia Treated by Both Open and
      Endovascular Surgeries.
AB  - BACKGROUND: Peripheral arterial disease (PAD) affects 3%-10% of the population
      before the age of 70 years and 15%-20% after that age.The aim of the study was to
      compare the incidence of complications and secondary interventions in patients
      who underwent each type of treatment. METHODS: We analyzed 734 medical records of
      the Department of Surgery at the 4th Military Teaching Hospital in Wroclaw, In
      total, 394 were operated on with open surgery; an endarterectomy (59.39%), a
      vascular prosthesis implantation (31.01%), or both of these techniques (6.6%),
      and 340 patients had angioplasty with (50.59%) or without stenting (49.41%).
      RESULTS: There were no statistically significant differences in the incidence of
      corresponding complications. The exception was the infection of the wound;
      significantly fewer were reported in the case of endovascular procedures (p =
      0.0087). There were 12 occasions (3.53%) during endovascular surgeries when
      intraoperative conversion or re-operation using the open method occurred. In the
      case of open surgery, the mean hospital stay was 7.77 days (median: 8, mode: 8),
      while for endovascular management it was equal to 4.68 days (median: 4, mode: 3),
      p <0.0001. CONCLUSION: The endovascular method results in a similar re-operation
      rate and number of complications as open surgery.

PMID- 28496018
TI  - Effects of heat stress on bovine preimplantation embryos produced in vitro.
AB  - Summer heat stress decreases the pregnancy rate in cattle and has been thought to
      be associated with the early embryonic death caused by the elevation of maternal
      body temperature. In vitro cultures have been widely used for the evaluation of
      effects of heat stress on oocytes, fertilization, preimplantation, and embryonic
      development. Susceptibility to heat stress is present in developmental stages
      from oocytes to cleavage-stage (before embryonic gene activation, EGA) embryos,
      leading to a consequent decrease in developmental competence. On the other hand,
      advanced-stage embryos such as morula or blastocysts have acquired
      thermotolerance. The mechanism for the developmental stage-dependent change in
      thermotolerance is considered to be the accumulation of antioxidants in embryos
      in response to heat-inducible production of reactive oxygen species. The
      supplementation of antioxidants to the culture media has been known to neutralize
      the detrimental effects of heat stress. Besides, EGA could be involved in
      acquisition of thermotolerance in later stages of embryos. Morulae or blastocysts
      can repair heat-induced unfolded proteins or prevent DNA damage occurring in
      processes such as apoptosis. Therefore, embryo transfer (ET) that can bypass the
      heat-sensitive stage could be a good solution to improve the pregnancy rate under
      heat stress. However, frozen-thawed ET could not improve the pregnancy rate as
      expected. Frozen-thawed blastocysts were more sensitive to heat stress and showed
      less proliferation upon heat exposure, compared to fresh blastocysts. Therefore,
      further research is required to improve the reduction in pregnancy rates due to
      summer heat stress.

PMID- 28496019
TI  - Age-associated changes in granulosa cells and follicular fluid in cows.
AB  - Age-associated decline in oocyte quality is common in mammals. Oocytes take a
      long time to reach their full-grown size in large animals, and maternal physical
      conditions profoundly affect follicle development. Aging affects the oocyte
      itself as well as the surrounding environment, such as granulosa cells and
      follicular fluid. This review discusses age-associated changes that occur in
      granulosa cells and follicular fluid in cows and suggests that age-associated
      decline in granulosa cells and follicular fluid hampers proper oocyte
      development.

PMID- 28496020
TI  - Predictors of Long-Term Mortality in Patients With Acute Heart Failure.
AB  - To investigate parameters which were related with long-term mortality in patients
      hospitalized for acute heart failure (AHF).A total of 287 patients with AHF
      presenting to the First Affiliated Hospital of Nanjing Medical University were
      enrolled into the registry from April 2012 to January 2015. The primary endpoint
      was all-cause mortality within 1 year; the association between variables and
      prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue
      follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations
      were higher amongst deceased than among survivors (P < 0.001). Serum sodium
      concentrations of patients who died were lower (P < 0.001). In receiver operator
      characteristics (ROC) analyses, the area under the curve (AUC) values for NT
      proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI
      0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750),
      respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium
      were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression
      analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2
      (HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably
      predicted long-term mortality after multivariable adjustment.In patients with
      acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of
      1-year mortality.

PMID- 28496021
TI  - Feasibility and Safety of Transulnar Catheterization in Ipsilateral Radial Artery
      Occlusion.
AB  - To investigate the postprocedural cardiovascular events and vascular outcomes,
      including hand ischemia and neurological compromise, after transulnar (TU)
      catheterization in ipsilateral radial artery occlusion.Previous randomized trials
      have shown that the transulnar (TU) approach for coronary angiogram and
      intervention has safety and outcomes similar to those of the transradial (TR)
      approach. However, the safety of the TU procedure when ipsilateral radial artery
      occlusion occurs is unknown.We retrospectively reviewed 87 TU cases with
      ipsilateral radial artery occlusion confirmed by a forearm angiogram. Eighty
      percent of these patients had a history of ipsilateral radial artery cannulation
      or surgery. We avoided the use of over-sized sheaths or applied a sheathless
      approach during surgery.No ulnar artery occlusion was observed by subsequent
      Doppler ultrasound or pulse oximetry. No patient developed hand ischemia or
      serious complications requiring surgery or blood transfusion during the follow-up
      period of 32.2 +/- 24.0 months. Review of the preprocedural forearm angiograms
      showed that 95.7% of the patients possessed significant collaterals supplying
      flow from the interosseous artery to the occluded radial artery remnant. Thus,
      the blood circulation to the palmar arch and digital vessels was maintained even
      when the ulnar artery was temporarily occluded by an in-dwelling ulnar arterial
      sheath.TU catheterization was safe in patients with coexisting ipsilateral radial
      artery occlusions and feasible for use in complex intervention procedures.
      Cautious manipulation of ulnar artery cannulation and hemostasis helped decrease
      the risk of hand ischemia.

PMID- 28496022
TI  - Comparison of Efficacy and Safety of Azilsartan and Olmesartan in Patients With
      Essential Hypertension.
AB  - Many patients still have high blood pressure (BP) after treatment with
      angiotensin II type 1 (AT1) receptor blockers (ARBs). We compared the efficacy
      and safety of azilsartan to those of olmesartan in a prospective randomized
      clinical trial. Sixty-four hypertensive patients who were treated with ARBs other
      than azilsartan and olmesartan were enrolled in this study. We randomly assigned
      patients to changeover from their prior ARBs to either azilsartan or olmesartan,
      and followed the patients for 3 months. Systolic BP (SBP) in the azilsartan group
      was significantly decreased at 3 months, and diastolic BP (DBP) and pulse rate
      (PR) in the olmesartan group showed significant reductions after 3 months. There
      were no significant differences in DeltaSBP, DeltaDBP, or DeltaPR (Delta = the
      value at 3 months minus the value at 0 months) between the groups. Serum levels
      of creatinine (Cr), uric acid (UA), and potassium (K) in the azilsartan group
      significantly increased after 3 months. While the changes in Cr, UA, and K were
      within the respective normal ranges, DeltaSBP was positively associated with
      DeltaCr in the azilsartan group. In conclusion, there was no difference in the
      depressor effects of azilsartan and olmesartan, and there were no serious changes
      in biochemical parameters with azilsartan and olmesartan.

PMID- 28496023
TI  - Bilateral Coronary-Pulmonary Artery Fistulas in Pulmonary Atresia With
      Ventricular Septal Defect.
AB  - We present a very rare case of bilateral coronary to pulmonary artery fistulas
      associated with pulmonary atresia with ventricular septal defect. The courses of
      coronary to pulmonary artery fistulas have to be clearly delineated by detailed
      angiography prior to corrective surgery.

PMID- 28496024
TI  - A Survival Case of Fulminant Right-Side Dominant Eosinophilic Myocarditis.
AB  - A 59-year-old Japanese woman was admitted to a nearby hospital with dyspnea and
      general malaise. Transthoracic echocardiography revealed right ventricular (RV)
      dilatation with severely reduced systolic function and leftward shift of the
      intraventricular septum. She was initially diagnosed with acute right heart
      failure, and fell into cardiogenic shock requiring an intra-aortic balloon pump
      and inotropic agents. An endomyocardial biopsy (EMB) demonstrated extensive
      interstitial edema, infiltration of inflammatory cells including numerous
      eosinophils, and myocytolysis with eosinophil degranulation. She was
      histologically diagnosed with eosinophilic myocarditis. Steroid pulse therapy was
      initiated, and her hemodynamic status improved along with dramatic recovery of
      the RV function. EMB 6 days after the initiation of steroid pulse therapy showed
      the disappearance of infiltration and degranulation of eosinophils, although
      lymphocytic infiltration still remained. Positron emission tomography-computed
      tomography (PET/CT) 23 days after steroid pulse therapy showed an increased 18F
      FDG uptake in the intraventricular septum and left ventricle, suggesting
      persistent myocardial inflammation. She was then treated with a maintenance dose
      of prednisolone. She became free of symptoms and follow-up echocardiography
      showed normal cardiac function 3 months after the initiation of corticosteroid
      treatment. In addition, EMB and PET/CT showed no inflammation. This is the first
      case report of fulminant and right-sided dominant eosinophilic myocarditis
      successfully treated with corticosteroid.

PMID- 28496025
TI  - Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a
      Predominant Cardiac Phenotype.
AB  - Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by
      mutations in the GLA gene, encoding for the enzyme alpha-galactosidase A.
      Although hundreds of mutations in the GLA gene have been described, many of them
      are variants of unknown significance. Here we report a novel GLA mutation,
      p.Ile239Met, identified in a large Hungarian three-generation family with FD. A
      69 year-old female index patient with a clinical history of renal failure,
      hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in
      the GLA gene. Genetic screening identified a previously unreported heterozygous
      mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening
      indicated that altogether 6 family members carried the mutation (5 females, 1
      male, average age: 55 +/- 16 years). Three family members, including the index
      patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while
      two other family members were diagnosed with left ventricular hypertrophy. Taking
      affection status as the presence of hypertrophic cardiomyopathy, left ventricular
      hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the
      mutation. Linkage analysis of the family gave a two-point LOD score of 2.01
      between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels
      were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit
      of normal +2STD: <= 1.8 ng/mL). The GLA enzyme level was markedly reduced in the
      affected male family member (< 0.2 umol/L/hour; upper limit of normal +/- 2STD:
      >= 2.6 umol/L/hour). We conclude that the p. Ile239Met GLA mutation is a
      pathogenic mutation for FD associated with predominant cardiac phenotype.

PMID- 28496026
TI  - Computed tomography angiography reveals stenosis and aneurysmal dilation of an
      aberrant right subclavian artery causing systemic blood pressure misreading in an
      old Pekinese dog.
AB  - A 14-year-old dog weighing 4 kg presented with hypotension only in the right
      forelimb. Thoracic radiography revealed a round soft tissue opacity near the
      aortic arch and below the second thoracic vertebra on a lateral view. Three
      dimensional computed tomography angiography clearly revealed stenosis and
      aneurysmal dilation of an aberrant right subclavian artery. Stenosis and aneurysm
      of an aberrant subclavian artery should be included as a differential diagnosis
      in dogs showing a round soft tissue opacity near the aortic arch and below the
      thoracic vertebra on the lateral thoracic radiograph.

PMID- 28496027
TI  - Expression profile of matricellular proteins in hypertrophied right ventricle of
      monocrotaline-induced pulmonary hypertensive rats.
AB  - Matricellular proteins, a non-structural extracellular matrix (ECM) component,
      bind to and modulate various molecules including growth factor, cytokine,
      protease, other ECM components and cell membrane receptors. While most
      matricellular proteins are hardly expressed in normal adult tissue, they are re
      expressed in heart tissue during cardiac diseases. The present study aimed to
      clarify the mRNA expression profile of matricellular proteins [secreted protein
      acidic and rich in cysteine: SPARC, hevin, thrombospondin (TSP)-1, -2 and -4,
      CCN1 and 5, tenascin (Tn) C and N, periostin and osteopontin (OPN)] in
      hypertrophied right ventricle (RV) of monocrotaline (MCT)-induced pulmonary
      hypertensive rats. Male Wistar rats were intraperitoneally treated with MCT or
      saline. Two or three weeks after MCT treatment, echocardiography was performed,
      and mRNA expression of matricellular proteins was measured by real-time
      polymerase chain reaction. MCT (2 weeks) induced pulmonary hypertension, RV
      dysfunction and hypertrophy, which were all worsened 3 weeks after MCT treatment.
      Expression of mRNA for SPARC, hevin, TnC, TSP-1, -2 and -4, CCN1 and 5, periostin
      and OPN but not TnN was significantly upregulated in RV of MCT (2 weeks)-treated
      rats. Expression of mRNA for TSP-4, CCN1 and 5 and periostin was continuously
      increased in RV of MCT (3 weeks)-treated rats. The present study for the first
      time revealed the mRNA expression profile for matricellular proteins in RV of MCT
      treated rats for 2 or 3 weeks, which will be helpful to clarify the relationship
      for matricellular proteins and pathogenesis of MCT-induced RV hypertrophy.

PMID- 28496028
TI  - 10-year trends of educational differences in long sickness absence due to mental
      disorders.
AB  - OBJECTIVES: Mental disorders are a key cause of sickness absence (SA) and
      challenge prolonging working careers. Thus, evidence on the development of SA
      trends is needed. In this study, educational differences in long SAs due to
      mental disorders were examined in two age groups among employees of the City of
      Helsinki from 2004 to 2013. METHODS: All permanently and temporarily employed
      staff aged 18-34 and 35-49 were included in the analyses (n=~27800 per year). SA
      spells of >=14 days due to mental disorders were examined annually. Education was
      classified to higher and lower levels. Joinpoint regression was used to identify
      major turning points in SA trends. RESULTS: Joinpoint regression models showed
      that lower educated groups had more long SAs spells due to mental disorders than
      those groups with higher education. SA trends decreased during the study period
      in all studied age and educational groups. Lower educated age groups had similar
      SA trends. Younger employees with higher education had the fewest SAs.
      CONCLUSIONS: A clear educational gradient was found in long SAs due to mental
      disorders during the study period. SA trends decreased from 2004 to 2013.

PMID- 28496029
TI  - A Newly Established Severity Scoring System in Predicting the Prognosis of
      Patients with Severe Fever with Thrombocytopenia Syndrome.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
      disease caused by novel Bunyavirus. Due to the peculiarity of SFTS, accurate
      assessment is difficult to achieve with the current score systems. This study
      aimed to establish a new severity scoring system in predicting the prognosis of
      patients with SFTS. We included 123 patients with SFTS: 92 patients (45 males and
      47 females), aged 59 +/- 12 years, in survive group and 31 patients (17 males and
      14 females), aged 61 +/- 10 years, in death group. The lactate dehydrogenase
      (LDH), the activated partial thromboplastin time (APTT), the saturation of pulse
      oximeter oxygen (SpO2) and Glasgow Coma Scale (GCS) were measured. SFTS severity
      scoring system was set up based on the above four factors and compared with the
      Rapid Emergency Medicine Scores (REMS) and Acute Physiology and Chronic Health
      Evaluation (APACHE II) Scores. Four parameters in the death group were all
      significantly higher than survival group. The areas under the curves (AUC) of
      REMS, APACHE II scores and SFTS severity scores were 0.734, 0.746 and 0.780
      respectively. The Youden index of the SFTS severity score was the highest among
      all the three scores (P < 0.01). If 15 was used as the cutoff value, the
      sensitivity and specificity of SFTS severity score in predicting the death risk
      for the patients were 74.2% and 76.1% respectively. The newly established SFTS
      severity scoring system is more efficient to predict the prognosis of patients
      with SFTS, compared with REMS and APACHE II.

PMID- 28496030
TI  - Underuse of Cardiac Rehabilitation in Workers With Coronary Artery Disease -
      Claims Database Survey in Japan.
AB  - BACKGROUND: Workers with coronary artery disease (CAD) require evidence-based
      care in order to return to work safely. We assessed the use of cardiac
      rehabilitation (CR) among workers with CAD, and identified the factors associated
      with CR use.Methods and Results:A retrospective cohort study based on data from a
      health insurance claims database was conducted. We identified workers aged >=18
      years who underwent percutaneous coronary intervention (PCI) or coronary artery
      bypass grafting (CABG) between 2006 and 2013, and reviewed the utilization of
      inpatient or outpatient CR. Logistic regression was used to identify the factors
      associated with CR use. A total of 1,699 patients were included. The frequency of
      inpatient and outpatient CR use was 23.7% (n=402) and 4.2% (n=72), respectively.
      Patients diagnosed with ST-elevated myocardial infarction were most likely to
      receive inpatient CR, and patients undergoing CABG were more likely to receive
      inpatient CR than those undergoing PCI. Moreover, inpatient CR use was associated
      with longer hospitalization duration, catecholamine use, and no history of
      chronic kidney disease. Furthermore, both unstable and stable angina were
      negatively correlated with outpatient CR use. CONCLUSIONS: Most of the Japanese
      workers with CAD in this study did not undergo CR. The type of CAD was strongly
      associated with inpatient and outpatient CR use. Thus, a strong evidence-practice
      gap exists in secondary preventative care within this group of patients.

PMID- 28496031
TI  - Atrial Septostomy for Left Atrial Decompression During Extracorporeal Membrane
      Oxygenation by Inoue Balloon Catheter.
AB  - BACKGROUND: Refractory pulmonary edema is an infrequent but serious complication
      in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO)
      for myocardial failure. Left atrial (LA) decompression in this setting is
      important. Although a few methods have been reported, the experience is mostly
      limited to children. We aimed to evaluate the feasibility of Inoue balloon
      catheter in percutaneous trans-septal LA decompression in adult cardiogenic
      patients.Methods and Results:We retrospectively analyzed 16 procedures of trans
      septal LA decompression by Inoue balloon catheter in 15 VA-ECMO patients (aged 22
      65 years, 6 men) with refractory pulmonary edema from May 2012 to December 2014.
      Mean left ventricular ejection fraction was 15%. The cause of cardiogenic shock
      included 7 cases of ischemic heart disease, 1 of dilated cardiomyopathy, 5 of
      myocarditis, and 2 of fatal ventricular arrhythmia.The procedures were performed
      4.3 days after ECMO. Inoue balloon size was 24-27 mm. LA septostomy were
      successfully created in 14 patients. Procedure time on average was 36.8 min
      (range, 15-85 min). There were no procedure-related complications.Radiography on
      the next day showed rapid resolution of pulmonary edema. CONCLUSIONS: Trans
      septal LA decompression by Inoue balloon catheter is a feasible alternative
      method for adult patients with refractory pulmonary edema under ECMO.

PMID- 28496032
TI  - Farnesoid X receptor regulates the growth of renal adenocarcinoma cells without
      affecting that of a normal renal cell-derived cell line.
AB  - The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor which is
      abundant in the liver, intestine, and kidney. FXR is a pivotal factor in
      cholesterol/bile acid homeostasis but is involved in the growth of hepatocellular
      carcinoma cells. In the present study, we investigated whether FXR is also
      involved in the growth of renal adenocarcinoma cells. The cell growth of renal
      adenocarcinoma cell line ACHN was inhibited by FXR knockdown and stimulated by
      FXR ligand, while that of a normal renal cell-derived cell line, HK-2, was not
      affected. The carcinoma-specific stimulation of cell growth by FXR was found to
      arise from down-regulation of p53 and p21/Cip1 mRNA expression. Our study showed
      that FXR stimulates proliferation of renal adenocarcinoma cells and that FXR
      knockdown is useful for growth suppression of renal adenocarcinoma without
      cytotoxicity to normal renal cells.

PMID- 28496033
TI  - Joint toxicity of fluoroquinolone and tetracycline antibiotics to zebrafish
      (Danio rerio) based on biochemical biomarkers and histopathological observation.
AB  - Herein, we report on the joint toxicity of four fluoroquinolones and two
      tetracyclines (beta-diketone antibiotics-DKAs) to zebrafish based on a series of
      toxicological endpoints and histopathological observations. A positive dose
      dependence was observed in DKA-exposure groups with a 72-hpf EC50 of 130.3 mg/L
      for hatching rate, 120-hpf LC50 of 149.8 mg/L, and 120-hpf EC50 of 135.1 mg/L for
      malformation rate. When zebrafish at 60 dpf were exposed to a series of DKA
      concentrations (45, 60 and 90 mg/L) for 7, 14 and 21 days, creatine kinase and
      AChE activities were significantly induced, and intracellular malondialdehyde
      increased in all treatments except for the 45 mg/L treatment. The transcription
      levels of AHRRa from livers were significantly (p < 0.05) up-regulated in all
      treatments after two months of DKA exposure. CKma expression from skeletal muscle
      was significantly down-regulated in the 90 mg/L treatment. A remarkable down
      regulation of CYP3A65 was observed in the 60 mg/L treatment. DKA exposure
      resulted in severe tissue damage including mitochondria swelling, reduction of
      mitochondrial cristae, deepening of mitochondrial cristae bands, and decreasing
      and even disappearance of the rough endoplasmic reticulum. Total sperm motility
      was decreased by ca. 30% due to DKA exposure. These results provide important
      information for toxicity and health risks due to mixed DKA exposure in aquatic
      environments.

PMID- 28496034
TI  - Effect of perinatal exposure to Bisphenol-A on DNA methylation and histone
      acetylation in cerebral cortex and hippocampus of postnatal male mice.
AB  - Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the
      production of polycarbonate plastics and epoxy resins. Recently we have reported
      that perinatal BPA exposure impaired spatial memory through upregulation of
      synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism
      is a key regulator of memory, we hypothesized that BPA might influence memory
      through epigenetic regulation of gene expression. Here we provide evidence that
      perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation
      in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice. BPA
      exposure also increased mRNA levels of DNMT1 and DNMT3a in cerebral cortex of 3
      and 8 weeks; whereas in hippocampus DNMT1 mRNA increased in 3 weeks but decreased
      in 8 weeks and DNMT3a showed no change. Further, HDAC2 mRNA and protein increased
      in cerebral cortex of both ages and in hippocampus it increased in 3 weeks but
      decreased in 8 weeks. Altogether, our results demonstrate that the perinatal BPA
      exposure induces epigenetic changes that possibly underlie the enduring effect of
      BPA on brain function and behavior.

PMID- 28496035
TI  - Alleviating effects of artificial tear instillation on S-1-induced ocular
      toxicity in dogs.
AB  - S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil
      potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and
      resectable gastric cancer. However, the extensive use of S-1 in clinical practice
      results in watery eyes, a serious clinical problem, which worsens patients'
      quality of life. Although repeated instillation of artificial tears is
      recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not
      been established. In the present study, we evaluated the alleviating effects of
      repeated artificial tear instillation on S-1-induced ocular toxicity in dogs. Ten
      beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1
      for up to 21 days. Five drops of artificial tears were instilled to the left eye,
      eight times daily, within 6 hr after S-1 administration. The mean cornea staining
      score tended to be low in the left eye with repeated artificial tear
      instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was
      more than 2-fold lower than that of the right eye. The incidence of dogs
      indicating normal tear drainage increased and stenosed tear drainage decreased by
      repeated artificial tear instillation. In conclusion, we demonstrated that
      artificial tear instillation can alleviate corneal surface damage induced by S-1
      in dogs.

PMID- 28496037
TI  - Mono-butyl phthalate-induced mouse testis injury is associated with oxidative
      stress and down-regulated expression of Sox9 and Dazl.
AB  - Mono-butyl phthalate (MBP) has reproductive toxicity but the related mechanisms
      have not been fully elucidated in vivo. We exposed male Balb/c mice to MBP by
      gavage at doses of 0, 25, 50, 100, 200 mg/kg for 14 days, and then evaluated the
      testicular alterations at the histological and molecular levels. MBP reduced
      mouse sperm count along with sperm malformation and seminiferous tubule
      degeneration in a dose-dependent manner. MBP dosed at 200 mg/kg significantly
      increased reactive oxygen species and malondialdehyde content in mouse testes.
      High doses of MBP (200 mg/kg) also significantly reduced mRNA expressions of
      testis growth and function related genes (Sox9 and Dazl). Our findings suggest
      that oxidative stress and down-regulated expression of Sox9 and Dazl may play
      important roles in MBP-induced testis injury.

PMID- 28496036
TI  - Tissue toxicokinetics of perfluoro compounds with single and chronic low doses in
      male rats.
AB  - To examine the kinetics of low doses of perfluoro compounds (PFCs), we
      administered perfluorohexanoic acid (C6A), perfluorooctanoic acid (C8A),
      perfluorononanoic acid (C9A) and perfluorooctane sulfonate (C8S) with a single
      oral dose (50-100 MUg/kg BW), and in drinking water at 1, 5, and 25 MUg/L for one
      and three months to male rats; and examined the distribution in the brain, heart,
      liver, spleen, kidney, whole blood and serum. C6A was very rapidly absorbed,
      distributed and eliminated from the tissues with nearly the same tissue t1/2 of 2
      3 hr. Considering serum Vd, and the tissue delivery, C6A was mainly in the serum
      with the lowest delivery to the brain; and no tissue accumulation was observed in
      the chronic studies as estimated from the single dose study. For the other PFCs,
      the body seemed to be an assortment of independent one-compartments with a longer
      elimination t1/2 for the liver than the serum. The concentration ratio of
      liver/serum increased gradually from C0 to a steady state. The high binding
      capacity of plasma protein may be the reason for the unusual kinetics, with only
      a very small fraction of free PFCs moving gradually to the liver. Although the
      tissue specific distribution was time dependent and different among the PFCs, the
      Vd and ke of each tissue were constant throughout the study. The possibility of
      extremely high C6A accumulation in the human brain and liver was suggested, by
      comparing the steady state tissue concentration of this study with the human data
      reported by Perez et al. (2013).

PMID- 28496038
TI  - Methylmercury induces hyaluronan synthesis in cultured human brain microvascular
      endothelial cells and pericytes via different mechanisms.
AB  - In a cerebrum damaged by methylmercury, where neuropathological lesions tend to
      localize along deep sulci and fissures, edematous changes in white matter have
      been proposed as the cause of such localization. Since hyaluronan has a high
      water-retention capability and can contribute to the progression of edematous
      changes, we hypothesize that methylmercury increases hyaluronan in brain
      microvascular cells. Our experimental results indicate that methylmercury induces
      the expression of hyaluronan in cultured human microvascular endothelial cells
      and pericytes through the induction of expressed UDP-glucose dehydrogenase and
      hyaluronan synthase 2, respectively. After exposure to methylmercury, hyaluronan
      largely accumulates in perivascular space, where it contributes to the
      progression of edematous changes.

PMID- 28496039
TI  - Pyrolysis of UR-144, a synthetic cannabinoid, augments an affinity to human CB1
      receptor and cannabimimetic effects in mice.
AB  - Drug abusers most often smoke 'herbal incense' as a cigarette or inhale it using
      a smoking tool. Smoking may cause pyrolysis of the drug and produce decomposed
      products of which biological effect has never been investigated. The synthetic
      cannabinoid UR-144 is known to undergo thermal degradation, giving a ring-opened
      isomer, so-called UR-144 degradant. The present study demonstrates by using UR
      144 as a model drug that the smoke of burned UR-144 contains the UR-144
      degradant. The UR-144 degradant showed approximately four fold higher agonist
      activity to human CB1 receptor and augmented hypothermic and akinetic actions in
      mice compared to UR-144. These results indicate that smoking behavior may
      increase psychological actions of the certain synthetic cannabinoids.

PMID- 28496041
TI  - A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy
      metabolism.
AB  - Drug-induced liver injury is a major cause of safety-related drug-marketing
      withdrawals. Several drugs have been reported to disrupt mitochondrial function,
      resulting in hepatotoxicity. The development of a simple and effective in vitro
      assay to identify the potential for mitochondrial toxicity is thus desired to
      minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in
      vitro test method called the "glucose-galactose" assay is often used in drug
      development but requires prior-culture of cells over several passages for
      mitochondrial adaptation, thereby restricting use of the assay. Here, we report a
      rapid version of this method with the same predictability as the original method.
      We found that replacing the glucose in the medium with galactose resulted in
      HepG2 cells immediately shifting their energy metabolism from glycolysis to
      oxidative phosphorylation due to drastic energy starvation; in addition, the
      intracellular concentration of ATP was reduced by mitotoxicants when glucose in
      the medium was replaced with galactose. Using our proposed rapid method,
      mitochondrial dysfunction in HepG2 cells can be evaluated by drug exposure for
      one hour without a pre-culture step. This rapid assay for mitochondrial toxicity
      may be more suitable for high-throughput screening than the original method at an
      early stage of drug development.

PMID- 28496040
TI  - Induction of human cytochrome P450 3A enzymes in cultured placental cells by
      thalidomide and relevance to bioactivation and toxicity.
AB  - Evidence has been presented for auto-induced human cytochrome P450 3A enzyme
      involvement in the teratogenicity and clinical outcome of thalidomide due to
      oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers.
      In this study, more relevant human placenta preparations and placental BeWo cells
      showed low but detectable P450 3A4/5 mRNA expression and drug oxidation
      activities. Human placental microsomal fractions from three subjects showed
      detectable midazolam 1'- and 4-hydroxylation and thalidomide 5-hydroxylation
      activities. Human placental BeWo cells, cultured in the recommended media, also
      indicated detectable midazolam 1'- and 4-hydroxylation and thalidomide 5
      hydroxylation activities. To reduce any masking effects by endogenous hormones
      used in the recommended media, induction of P450 3A4/5 mRNA and oxidation
      activities were measured in placental BeWo cells cultured with a modified medium
      containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly
      induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold,
      but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media
      conditions. Under these modified conditions, thalidomide also significantly
      induced midazolam 1'-hydroxylation and thalidomide 5-hydroxylaion activities 3
      fold but not bupropion hydroxylation activity. Taken together, activation of
      thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in
      human placentas, as well as livers, is suggested in vivo.

PMID- 28496042
TI  - High sensitivity of testicular function to titanium nanoparticles.
AB  - Titanium dioxide nanoparticles (TiNPs) present toxicity in organs such as the
      liver, lung, and intestine. The testis has also been reported as a target organ
      of TiNPs. We recently reported that TiNPs had no genotoxic effect in the liver
      and bone marrow, while showing clear testicular dysfunction. In this paper,
      therefore, we systematically compared the sensitivity of hepatic function using
      biochemical markers and testicular function against TiNPs. Male C57BL/6J mice
      were injected intravenously with TiNPs (Aeroxide-P25, at doses of 0.1, 1, 2, and
      10 mg/kg body weight) once per week for 4 consecutive weeks. Mice were sacrificed
      three days after the last injection. Body weights, liver weights, and testicular
      related organ weights were not found to be changed by TiNP treatment. Moreover,
      TiNPs caused no hepatic damage, as evaluated by alanine aminotransferase and
      aspartate aminotransferase indexes. The testicular function, however, was clearly
      impaired by TiNP treatment; reduction in two sperm motion parameters (motile
      percent and progressive percent) and sperm numbers in cauda epididymides was
      seen. We observed Ti accumulation in the liver but not in the testis, as well as
      no change in plasma levels of sex hormones related to spermatogenesis. Our
      findings indicate that the testis is highly sensitive to TiNPs, as compared to
      the liver. We believe that, when considering the biological effects of TiNPs,
      testicular function (especially motility ability) may be a sensitive indicator.

PMID- 28496043
TI  - Length effects of single-walled carbon nanotubes on pulmonary toxicity after
      intratracheal instillation in rats.
AB  - We aimed to evaluate the effects of the length of single-walled carbon nanotubes
      (SWCNTs) on pulmonary toxicity in rats. Each rat received a single intratracheal
      instillation of short (S-) (average length of 0.40 MUm) or long (L-) (average
      length of 2.77 MUm) SWCNTs at a dose of 1 mg/kg and was observed for the next 6
      months. Neither S- nor L-SWCNTs affected clinical signs, body weight, or autopsy
      findings. An increase in lung weight was observed after instillation of S- or L
      SWCNTs; however, lung weights were slightly higher in the rats that were
      administered the S-SWCNTs. Distinct differences in bronchoalveolar lavage fluid
      (BALF) composition were observed between the S- and L-SWCNT-treated rats as early
      as 7 days after the intratracheal instillations of the SWCNTs. The S-SWCNTs
      caused persistent lung injury and inflammation during the 6-month observational
      period. However, the L-SWCNTs induced minimal lung injury and inflammation.
      Although the S- and L-SWCNTs changed BALF parameters and histopathological
      features of the lung, the magnitudes of the changes observed after the S-SWCNT
      treatment were greater than the respective changes observed after the L-SWCNT
      treatment. These findings indicate that the severity of the pulmonary toxicity
      caused after intratracheal instillation of SWCNT depends on the length of the
      SWCNTs. It appears that shorter SWCNTs induce greater pulmonary toxicity than
      longer SWCNTs do.

PMID- 28496044
TI  - Comparison of nephrotoxicity between two gadolinium-contrasts, gadodiamide and
      gadopentetate in patients with mildly diminished renal failure.
AB  - Although gadolinium (Gd)-based contrast media have been found to be nephrotoxic,
      their nephrotoxicity, and the dependence of nephrotoxicity on chelate types, have
      not been assessed in patients with normal or mildly diminished renal failure.
      This prospective, randomized study compared the nephrotoxicity of low doses of
      the nonionic Gd-based contrast medium gadodiamide (Omniscan(r)) and the ionic Gd
      based contrast medium gadopentetate (Magnevist(r)) in patients with serum
      creatinine < 1.6 mg/dL. Patients aged 20 to 80 years, weighing 45 to 70 kg and
      with normal or < 1.6 mg/dL Serum-creatinine in the 3 months prior to undergoing
      magnetic resonance imaging (MRI) of brain, were enrolled. Patients were
      randomized to receive 0.1 mol/kg gadodiamide or gadopentetate. Serum-creatinine,
      serum cystatin-C, estimated glomerular filtration rate (eGFR) using the
      Modification of Diet in Renal Disease (MDRD) formula, and estimated creatinine
      clearance rate (eCCr) using the Cockcroft-Gault formula were measured just before
      and 16-80 hr after MRI. Groups were compared statistically by Mann-Whitney U
      tests and Wilcoxon signed-rank tests. There were no significant differences in
      clinical characteristics between the gadodiamide (n = 43) and gadopentetate (n =
      59) groups. Serum-creatinine, eGFR and eCCr before and 16-80 hr after MRI did not
      differ significantly within either group or between the two groups. Serum
      cystatin-C was significantly higher 16-80 hr after than before MRI only in the
      gadodiamide group (0.79 +/- 0.21 vs. 0.74 +/- 0.14 mg/L, p = 0.028). The ionic
      contrast medium, gadopentetate, did not affect renal function during MRI, whereas
      the nonionic contrast medium, gadodiamide, affected renal function transiently.

PMID- 28496046
TI  - Soluble Vascular Cell Adhesion Molecule and Cardiovascular Disease: An
      Epidemiological View.

PMID- 28496045
TI  - Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty
      Liver Disease in Microminipigs.
AB  - AIM: We have recently established a novel swine model for studies of
      atherosclerosis using MicrominipigsTM (uMPs) fed a high-fat/high-cholesterol diet
      (HcD). Using this swine model, we re-evaluated the effects of dietary cholic acid
      (CA) on serum lipid profile, atherosclerosis and hepatic injuries. METHODS: The
      uMPs were fed HcD supplemented with 0.7% CA (HcD+CA) for eight weeks, and the
      effect of CA on serum lipoprotein levels, expression of oxidative stress markers,
      adiposity and lesion formation in the aorta, liver, and other organs was
      investigated. RESULTS: The HcD+CA-fed group exhibited more visceral adiposity,
      progression of atherosclerosis and higher serum levels of oxidative stress
      markers than the HcD-fed group, even though they showed similar serum lipid
      levels. The liver demonstrated increased lipid accumulation, higher expression of
      oxidative stress markers, accelerated activation of foamy Kupffer cells and
      stellate cells, and increased hepatocyte apoptosis, indicating non-alcoholic
      fatty liver disease (NAFLD). Intriguingly, foamy macrophage mobilization was
      observed in various organs, including the reticuloendothelial system, pulmonary
      capillary vessels and skin very often in HcD+CA-fed uMPs. CONCLUSION: To our
      knowledge, this is the first large animal model, in which visceral obesity, NAFLD
      and atherosclerosis are concomitantly induced by dietary manipulation. These data
      suggest the detrimental effects of CA, potentially through local and systemic
      activation of oxidative stress-induced signaling to macrophage mobilization, on
      the acceleration of visceral adiposity, atherosclerosis and NAFLD.

PMID- 28496047
TI  - Histopathology of Asymptomatic Iliac Atherosclerosis: From Autopsy to Practice.

PMID- 28496048
TI  - Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Stroke.

PMID- 28496049
TI  - Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Stroke - Reply.

PMID- 28496050
TI  - Multiple system atrophy: clinicopathological characteristics in Japanese
      patients.
AB  - Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that
      has both clinical and pathological variants. Clinical examples include MSA with
      predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA
      P), whereas olivopontocerebellar atrophy and striatonigral degeneration represent
      pathological variants. We performed systematic reviews of studies that addressed
      the relative frequencies of clinical or pathological variants of MSA in various
      populations to determine the clinicopathological characteristics in Japanese MSA.
      The results revealed that the majority of Japanese patients have MSA-C, while the
      majority of patients in Europe and North America have MSA-P. A comparative study
      of MSA pathology showed that the olivopontocerebellar-predominant pathology was
      more frequent in Japanese MSA than in British MSA. Demonstrated differences in
      pathological subtype thus appear consistent with differences in the clinical
      subtype of MSA demonstrated between Japan and European populations. We concluded
      that olivopontocerebellar-predominant pathology and MSA-C may represent
      clinicopathological characteristics in Japanese MSA. Factors determining
      predominant involvement of olivopontocerebellar regions in MSA should therefore
      be explored.

PMID- 28496051
TI  - Molecular investigations of development and diseases of the brain of higher
      mammals using the ferret.
AB  - The brains of higher mammals such as primates and carnivores contain well
      developed unique brain structures. Uncovering the physiological functions,
      developmental mechanisms and evolution of these brain structures would greatly
      facilitate our understanding of the human brain and its diseases. Although the
      anatomical and electrophysiological features of these brain structures have been
      intensively investigated, our knowledge about their molecular bases is still
      limited. To overcome this limitation, genetic techniques for the brains of
      carnivores and primates have been established, and molecules whose expression
      patterns correspond to these brain structures were identified recently. To
      investigate the functional roles of these molecules, rapid and efficient genetic
      manipulation methods for higher mammals have been explored. In this review,
      recent advances in molecular investigations of the brains of higher mammals are
      discussed, mainly focusing on ferrets (Mustela putorius furo).

PMID- 28496052
TI  - Data management issues in mobile ad hoc networks.
AB  - Research on mobile ad hoc networks (MANETs) has become a hot research topic since
      the middle 1990's. Over the first decade, most research focused on networking
      techniques, ignoring data management issues. We, however, realized early the
      importance of data management in MANETs, and have been conducting studies in this
      area for 15 years. In this review, we summarize some key technical issues related
      to data management in MANETs, and the studies we have done in addressing these
      issues, which include placement of data replicas, update management, and query
      processing with security management. The techniques proposed in our studies have
      been designed with deep considerations of MANET features including network
      partitioning, node participation/disappearance, limited network bandwidth, and
      energy efficiency. Our studies published in early 2000's have developed a new
      research field as data management in MANETs. Also, our recent studies are
      expected to be significant guidelines of new research directions. We conclude the
      review by discussing some future directions for research.

PMID- 28496054
TI  - Days weaving the lagging strand synthesis of DNA - A personal recollection of the
      discovery of Okazaki fragments and studies on discontinuous replication
      mechanism.
AB  - At DNA replication forks, the overall growth of the antiparallel two daughter DNA
      chains appears to occur 5'-to-3' direction in the leading-strand and 3'-to-5'
      direction in the lagging-strand using enzyme system only able to elongate 5'-to
      3' direction, and I describe in this review how we have analyzed and proved the
      lagging strand multistep synthesis reactions, called Discontinuous Replication
      Mechanism, which involve short RNA primer synthesis, primer-dependent short DNA
      chains (Okazaki fragments) synthesis, primer removal from the Okazaki fragments
      and gap filling between Okazaki fragments by RNase H and DNA polymerase I, and
      long lagging strand formation by joining between Okazaki fragments with DNA
      ligase.

PMID- 28496053
TI  - Chemical and structural biology of protein lysine deacetylases.
AB  - Histone acetylation is a reversible posttranslational modification that plays a
      fundamental role in regulating eukaryotic gene expression and chromatin
      structure/function. Key enzymes for removing acetyl groups from histones are
      metal (zinc)-dependent and NAD+-dependent histone deacetylases (HDACs). The
      molecular function of HDACs have been extensively characterized by various
      approaches including chemical, molecular, and structural biology, which
      demonstrated that HDACs regulate cell proliferation, differentiation, and
      metabolic homeostasis, and that their alterations are deeply involved in various
      human disorders including cancer. Notably, drug discovery efforts have achieved
      success in developing HDAC-targeting therapeutics for treatment of several
      cancers. However, recent advancements in proteomics technology have revealed much
      broader aspects of HDACs beyond gene expression control. Not only histones but
      also a large number of cellular proteins are subject to acetylation by histone
      acetyltransferases (HATs) and deacetylation by HDACs. Furthermore, some of their
      structures can flexibly accept and hydrolyze other acyl groups on protein lysine
      residues. This review mainly focuses on structural aspects of HDAC enzymatic
      activity regulated by interaction with substrates, co-factors, small molecule
      inhibitors, and activators.

PMID- 28496057
TI  - Optical Elemental Analysis of Metals Using Shewanella oneidensis.
AB  - A simple method for the detection of metal ions in solution is proposed, using
      Shewanella oneidensis, which has the ability to reduce metal ions into metal
      nanoparticles on the cell surface. The method can be used to identify metal ions
      in solution using the light-scattering characteristics of the metal nanoparticles
      formed on the cells.

PMID- 28496056
TI  - Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines.
AB  - Recent studies have indicated the significance of immune checkpoint molecules
      including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4,
      and T-cell immunoglobulin and mucin domain-containing molecule-3 for anti-tumor
      immune responses. We previously investigated PD-1 ligand 1/2 (PD-L1/2) expression
      in lymphoma cell lines, and found that PD-L1/2 is expressed on the adult T-cell
      leukemia/lymphoma (ATL-T) and B-cell lymphoma (SLVL) cell lines. In the present
      study, we investigated whether the Stat3 inhibitor WP1066 abrogated PD-L1/2
      expression in lymphoma cell lines. Incubation with WP1066 inhibited lymphoma cell
      growth and induced cell apoptosis. PD-L1/2 expression in the ATL-T, SLVL, and
      human brain malignant lymphoma (HKBML) cell lines was significantly abrogated by
      WP1066 treatment. These data indicated that a Stat3 inhibitor abrogated PD-L1/2
      expression in lymphoma cells. Such an inhibitor is therefore considered to be
      useful for additional immunotherapy in patients with advanced lymphoma.

PMID- 28496055
TI  - Organization and dynamics of yeast mitochondrial nucleoids.
AB  - Mitochondrial DNA (mtDNA) is packaged by association with specific proteins in
      compact DNA-protein complexes named mitochondrial nucleoids (mt-nucleoids). The
      budding yeast Saccharomyces cerevisiae is able to grow either aerobically or
      anaerobically. Due to this characteristic, S. cerevisiae has been extensively
      used as a model organism to study genetics, morphology and biochemistry of
      mitochondria for a long time. Mitochondria of S. cerevisiae frequently fuse and
      divide, and perform dynamic morphological changes depending on the culture
      conditions and the stage of life cycle of the yeast cells. The mt-nucleoids also
      dynamically change their morphology, accompanying morphological changes of
      mitochondria. The mt-nucleoids have been isolated morphologically intact and
      functional analyses of mt-nucleoid proteins have been extensively performed.
      These studies have revealed that the functions of mt-nucleoid proteins are
      essential for maintenance of mtDNA. The aims of this review are to summarize the
      history on the research of yeast mt-nucleoids as well as recent findings on the
      organization of the mt-nucleoids and mitochondrial dynamics.

PMID- 28496058
TI  - Derivatization-based High-throughput Bioanalysis by LC-MS.
AB  - Liquid chromatography coupled with mass spectrometry (LC-MS) is one of the most
      prominent analytical techniques due to its inherent selectivity and sensitivity.
      LC-MS is currently the first choice for high-throughput bioanalysis due to the
      advancements in MS instruments and the analytical software. Based on this
      situation, we are developing various types of derivatization reagents, including
      chiral reagents for MS and/or MS/MS detection. These developed reagents are
      adopted for the detection of biomarker candidates related to diseases. The
      biomarker candidates include not only achiral molecules, but also chiral ones.
      Although determining the already-identified chiral molecules is relative easy, it
      is very difficult to identify and/or determine unknown enantiomer(s) in real
      samples. To solve this difficulty, we proposed a new strategy to identify unknown
      enantiomeric biomarkers related to diseases. This review paper deals with the
      development of derivatization reagents for amines and carboxylic acids in LC-MS
      analysis and their application to bioanalysis.

PMID- 28496059
TI  - Rapid Photoluminescence Quenching Based Detection of Cu2+ in Aqueous Medium by
      CdS Quantum Dots Surface Passivated by Thiourea.
AB  - Presented here is a simple yet rapid and efficient analytical method for visual
      as well as spectroscopic method for sensing of trace concentrations of Cu2+ ions
      in aqueous medium by systematic photoluminescence quenching of a highly water
      soluble probe made of CdS quantum dots surface modified by thiourea. The salient
      features of this work describe rapid detection (2 min equilibration time) of Cu2+
      ions at wider linear concentration range (0.025 - 10 mg/L) corresponding to a
      sensitivity of 2.81(mg/L)-1 and limit of quantification of 47.3 MUg/L,
      respectively, suitable for Cu2+ sensing in drinking water and ground water.
      Further, the detection of Cu2+ ion was free from most interfering cations and
      anions, except for minor interference from Cr3+, Hg2+ and Pb2+. The robustness of
      our probe for Cu2+ sensing is demonstrated from efficient Cu2+ spike recovery
      analysis in groundwater and river water samples.

PMID- 28496061
TI  - Application of Electron Paramagnetic Resonance and Solid-state 13C Nuclear
      Magnetic Resonance of Cross-polarization/Magic Angle Spinning to Study Enzymatic
      Degradation of Silk Fabrics.
AB  - The enzymatic degradation of silk by protease XIV has been investigated by using
      scanning electron microscopy (SEM), Fourier transfer infrared spectroscopy
      (FTIR), solid-state 13C nuclear magnetic resonance of cross-polarization/magic
      angle spinning (13C CP/MAS solid state NMR) and electron paramagnetic resonance
      (EPR). Micro-morphology of protease XIV aged samples showed that microfilaments
      were stripped out from the surface of silk fibers. The results of FTIR and 13C
      CP/MAS solid-state NMR indicated that the enzymatic degradation process could be
      divided into two stages. The EPR spectra indicated that the enzymatic degradation
      process was related to the free radical with the g-factor value of 2.0043. We
      also proposed that at the first degradation stage, the free radicals were apt to
      lose activities due to the loose structure of the non-crystalline region; at the
      second degradation stage, the free radicals produced in the crystalline region
      tended to be stored.

PMID- 28496060
TI  - Rapid Detection of Small Molecule Metabolites in Serum of Hepatocellular
      Carcinoma Patients Using Ultrafast Liquid Chromatography-Ion Trap-Time of Flight
      Tandem Mass Spectrometry.
AB  - A method was developed for analyzing broad spectrum small molecule metabolites in
      the serum of hepatocellular carcinoma (HCC) patients based on ultrafast liquid
      chromatography-ion trap-time of flight tandem mass spectrometry (UFLC-IT-TOF MS).
      Serum samples were collected from 80 HCC patients and healthy persons. After
      pretreatment process for protein precipitation, the supernatant was analyzed with
      the UFLC-IT-TOF MS to obtain information on the metabonomics of small molecules.
      The eight compounds of glycocholic acid, choline glycerophosphate, acetyl-L
      phenylalanine, oleamide, tetradecanamide, acetylcarnitine, lysolecithin and
      glycochenodeoxycholic acid in the HCC group were identified with significant
      differences from those in the health group (P <0.01). By using multidimensional
      analysis of variation coefficient and principal component analysis for the
      repeatability and 48 h stability, the method was demonstrated to have good
      repeatability, excellent precision, and high stability, which can satisfy the
      metabonomics research requirement. The high throughput and practical usability of
      the method further shows perspective for metabonomic analysis of large-batch
      serum samples.

PMID- 28496062
TI  - A Novel Electrochemical Sensor Based on [Ru(NH3)6]Cl3 as a Redox Indicator for
      the Detection of G-G Mismatched DNA.
AB  - In this paper, a novel electrochemical sensor was developed for the rapid
      detection of G-G mismatched DNA based on hexaammineruthenium(III) chloride
      ([Ru(NH3)6]Cl3) as a redox indicator. The sensor platform was constructed by
      immobilizing small molecules (NC-linker) on the gold electrode via amide bonds.
      The as-prepared NC-linker as the nucleic acids recognition molecule can interact
      with the G base of DNA. After the sensor was incubated with G-G mismatched DNA,
      the double-stranded DNA (dsDNA) acted as carriers of the signal tags
      [Ru(NH3)6]Cl3, which resulted in a remarkable electrochemical signal. More
      binding of [Ru(NH3)6]Cl3 led to increases of the electrochemical signal. Other
      mismatched DNA produced only a low response, as well as complementary DNA. Thus G
      G mismatched DNA can be easily discriminated from other mismatched and
      complementary DNA based on the sensor. Furthermore, the method was simple, rapid
      and repeatable for the detection of G-G mismatched DNA. The selective detection
      of target dsDNA was achieved by a relative current ratio of the target and
      control DNA. These results demonstrated that this strategy could provide great
      promise for the rapid and specific detection of other sequence-specific DNA.

PMID- 28496063
TI  - Fabrication of Water-soluble Fluorescent Polymeric Micelles for Selective
      Detection of Hg2+ in Blood Serum.
AB  - In this study, amphiphilic diblock copolymers were designed and synthesized via
      the incorporation of reversible addition-fragmentation chain transfer radical
      polymerization (RAFT) and a subsequent grafting technique. Subsequently, Hg2+
      sensitive water-soluble fluorescent polymeric micelles (FNs) were prepared by a
      reprecipitation strategy. The spectroscopic characteristics demonstrate that the
      fluorescein isothiocyanate (FITC) was successfully linked into the polymer. Due
      to the promoted reaction of desulfurization cyclization by Hg2+, the fluorescence
      of fluorescein in FNs was obviously quenched. The as-prepared FNs showed
      admirable Hg2+-sensitivity (detection limit: 54 nM), excellent water-solubility
      and high selectivity. In addition, FNs were successfully used to determine Hg2+
      in blood serum. We expected that the as-prepared FNs could perform potential
      applications in imaging, sensing, and bioanalytic chemistry.

PMID- 28496064
TI  - Colorimetric Ion Sensors Based on Polystyrenes Bearing Side Chain Triazole and
      Donor-Acceptor Chromophores.
AB  - Side chain clicked polystyrene derivatives formed by the Cu(I)-catalyzed azide
      alkyne cycloaddition (CuAAC) reaction showed colorimetric ion sensing behaviors
      when donor-acceptor chromophores, prepared by a [2+2] cylcoladdition
      retroelectrocyclization between electron-rich alkynes and tetracyanoethylene
      (TCNE)/7,7,8,8-tetracyanoquinodimethane (TCNQ), were attached to the triazole
      rings. The metal ion sensing behaviors could be explained according to the theory
      of hard and soft acids and bases (HSAB). Hard acidic metal ions were mainly
      recognized by the hard basic anilino-nitrogen moieties, resulting in a decrease
      in the charge-transfer (CT) bands. In contrast, soft acidic metal ions led to a
      bathochromic shift in the CT bands due to the selective interactions with the
      soft basic cyano-nitrogen atoms. With the triazole spacers, more soft (and/or
      borderline) metal ions were recognized by the donor-acceptor chromophores
      probably due to more space for the various sized metal ions. The chemodocimetric
      anion sensing behaviors of the clicked polystyrenes were almost the same as those
      of the counter polystyrenes without the triazole spacers. Overall, the triazoles
      in this study do not serve as colorimetric sensor units towards both metal ions
      and anions, but they are effective spacers between the polymer main chain and ion
      sensing donor-acceptor side chain chromophores.

PMID- 28496065
TI  - Solid Sampling in Analysis of Soils by Two-jet Plasma Atomic Emission
      Spectrometry.
AB  - The possibility of direct analysis of soils by two-jet plasma atomic emission
      spectrometry was investigated using certified reference materials of black earth,
      grey desert and red soils. It was shown that As, B, Cd, Cu, Hg, P, and V could be
      determined after a 2-fold, and Be, Co, Cr, Ga, Nb, Pb, and Zn-after a 10-fold
      dilution of the samples by a spectroscopic buffer using calibration samples based
      on graphite powder. The strongest matrix effects were revealed for red soil
      having the highest Al and Fe concentration, which led to the overstated
      concentrations of some elements. The overstating factor depended on analyte
      concentration and was no more than 2. A clear advantage of the suggested
      technique over existing methods is the simple sample preparation process, which
      requires no reagents except a spectroscopic buffer, and possibility of using the
      same calibration samples for analysis of different soils.

PMID- 28496066
TI  - Application of Deep Eutectic Solvents in Hybrid Molecularly Imprinted Polymers
      and Mesoporous Siliceous Material for Solid-Phase Extraction of Levofloxacin from
      Green Bean Extract.
AB  - Deep eutectic solvents (DES) are potential ecofriendly surfactants for the
      preparation of materials. In this study, both molecularly imprinted polymers
      (MIPs) and mesoporous siliceous materials (MSMs) were modified by betaine-based
      DES. Six materials were employed as solid phase extraction (SPE) adsorbents for
      the rapid purification of levofloxacin. The DES-based materials showed better
      selective adsorption than the conventional materials. The adsorption curves of
      DES-MIP showed superior molecular recognition ability and binding capability for
      levofloxacin compared to the other materials. The limit of detection and limit of
      quantitation of the method were 0.01 and 0.03 MUg/mL for levofloxacin,
      respectively. The method recoveries at three spiked levels were 97.2 - 100.2% for
      DES-MIP, with an RSD <1.8%. DES-MIP showed the highest selective recovery (95.2%)
      for levofloxacin from the green bean extract, and could remove the interferent
      effectively.

PMID- 28496067
TI  - Retention Behavior of Inorganic Anions in Hydrophilic Interaction Chromatography.
AB  - The retention behavior of inorganic anions was studied in hydrophilic interaction
      chromatography (HILIC). In this study, five kinds of HILIC stationary phases
      (amino, imidazole, amide, pyridine and zwitterionic) were investigated. It was
      found that only amino and imidazole columns exhibited the separation of inorganic
      anions under HILIC conditions. The retention mechanism was further investigated
      under both columns. A reversed elution order of inorganic anions was observed
      under the HILIC condition compared with those observed under the ion-exchange
      chromatography mode (IEC). The effect of salt species and their concentration in
      the eluent were investigated under constant acetonitrile (ACN) content. Sodium
      chloride and sodium perchlorate were chosen as the salt, and the salt (sodium
      perchlorate) concentration was varied from 10 to 40 mM to confirm the effect of
      the electrostatic interaction. The slope values of the plots of the log retention
      factor (k) versus the log eluent concentration were calculated to be between 
      0.43 and -0.45 for the amino column, while those obtained on the imidazole column
      were between -0.68 and -0.73. Various concentrations of ACN were also examined
      with 20 mM sodium perchlorate, and the typical HILIC retention behavior was
      observed on both amino and imidazole columns. Due to the obtained results, it is
      considered that the separation of inorganic anions under the HILIC condition was
      achieved by both electrostatic interaction and partition.

PMID- 28496068
TI  - The Use of a Gas Chromatography/Milli-whistle Technique for the On-line
      Monitoring of Ethanol Production Using Microtube Array Membrane Immobilized Yeast
      Cells.
AB  - Hollow, poly(L-lactic acid) microtube array membranes (MTAM) were used in
      preparing membranes that contained immobilized yeast cells. To evaluate the
      performance of the developed system for continuous and fed-batch fermentation, a
      gas chromatography/milli-whistle device was used to on-line monitor the
      production of ethanol. The milli-whistle was connected to the outlet of a GC
      capillary, and when the fermentation gases and the GC carrier gas passed through
      it, a sound with a fundamental frequency was produced. The online data obtained
      for frequency-change vs. retention time can be recorded after a fast Fourier
      transform. In typical bioethanol fermentation, the yeast cells cannot be
      recycled, whereas the artificial yeast-MTAMs can be. The hollow-MTAM containing
      immobilized yeast cells significantly enhanced to bioethanol productivity, and
      represent a novel, promising technology for bioethanol fermentation. Our data
      indicate that the gas chromatography/milli-whistle device, which is economical
      and stable, is a very useful detector for long-term monitoring.

PMID- 28496069
TI  - Optimization and Investigation of Zwitterionic Monolithic Stationary Phases for
      Capillary Ion Chromatography.
AB  - Zwitterionic monolithic columns were synthesized by a one-pot reaction using [2
      (methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, ethylene
      dimethacrylate, methanol and 2,2'-azobis(isobutyronitrile) as the monomer, cross
      linker, porogen and initiator, respectively. The optimum conditions for
      polymerization and the efficiency of the prepared columns were examined for ion
      chromatography. The separation of five kinds of inorganic anions was achieved.
      The back pressures were monitored as increasing flow-rate, and the resulting
      plate heights (i.e. height equivalent of a theoretical plate, HETP) of SCN- were
      calculated at the inspected flow-rates. It was found that the increment rates of
      both the back pressure and HETP were rather slight. Mobile phases containing
      various cations or acid increased the retention times of the anions. Divalent
      cations could be separated, while monovalent cations could not be resolved due to
      their weak retention on the stationary phases.

PMID- 28496070
TI  - Trace Elemental Determination Using a Portable Total Reflection X-Ray
      Fluorescence Spectrometer with a Collodion Film Sample Holder.
AB  - Using a portable total-reflection X-ray fluorescence (TXRF) spectrometer with a
      collodion film sample holder, a spectrum of an analyte containing 50 ng of
      aluminum was measured. The Al Kalpha line (1.49 keV) that partially overlaps with
      the Si Kalpha line (1.74 keV) from a quartz glass substrate usually used as a
      sample holder for TXRF analysis, was clearly detected when using the collodion
      film sample holder. To investigate the quantitative performance of the portable
      spectrometer with a collodion film sample holder, the concentrations of Cr, Mn,
      and Fe in a certified reference material of river water (JSAC 0302-3b), whose
      certified values are 10.0, 5.1, and 59.6 MUg/L, respectively, were determined by
      the internal-standard method. We showed that approximate concentrations of these
      elements were determined.

PMID- 28496071
TI  - Solubility-based Separation and Purification of Long-Chain Chitin
      Oligosaccharides with an Organic-Water Mixed Solvent.
AB  - A simple and rapid method for separation and purification of chitin
      oligosaccharides, (GlcNAc)n, with n >= 5 is presented. A commercially available
      chitin oligosaccharides sample, consisting of (GlcNAc)n with n = 1 - 7, was used
      as the starting material. Ten milligrams of the material was mixed with 100 MUL
      of the 1 mol/L HCl. All the (GlcNAc)n species were dissolved in the aqueous
      medium. The aqueous solution was mixed with 900 MUL of EtOH; the mixture was
      centrifuged, and the supernatant was removed to obtain a precipitate. The
      precipitate was found to consist mainly of (GlcNAc)n with n >= 5, indicating the
      significant difference in solubility between the short-chain (GlcNAc)n species
      with n <= 3 and the longer ones. By the repetition of the operations, a high
      purity long-chain (GlcNAc)n sample with n >= 5 could be prepared successfully.
      Since the long-chain (GlcNAc)n species are known to have excellent elicitor
      activity, this sample would be useful in the study of plant pathology, as well as
      chitin and chitosan chemistry.

PMID- 28496072
TI  - Improvement of Chromium(VI) Extraction from Acidic Solutions Using a Poly(vinyl
      chloride)-based Polymer Inclusion Membrane with Aliquat 336 as the Carrier.
AB  - An important reason for the inefficient extraction of Cr(VI) from its acidic
      solutions into polymer inclusion membranes (PIMs), consisting of poly(vinyl
      chloride) as the base-polymer and Aliquat 336 as the carrier, was found to be
      associated with the leaching of Aliquat 336 from the PIMs into the solutions,
      where it subsequently reduced the anionic Cr(VI) species to cationic Cr(III)
      species. The PIM extraction efficiency for Cr(VI) was significantly improved by
      the addition of NaNO3 to the solutions, which suppressed the leaching of Aliquat
      336 and the reduction of Cr(VI) to Cr(III).

PMID- 28496073
TI  - Mass Transfer in Mesoporous Microparticles Studied by Confocal Fluorescence
      Recovery after Photobleaching.
AB  - The intraparticle diffusion of a fluorescent dye in single microparticles in an
      aqueous solution was analyzed using fluorescence recovery after photobleaching,
      with a confocal fluorescence microscope. The fluorescence depth profile of single
      microparticles, and the fluorescence recovery at the particle center, were
      measured; further, the intraparticle diffusion coefficient was determined through
      simulations of three-dimensional diffusion in the respective microparticles. The
      intraparticle diffusion of coumarin 102 in octadecylsilyl silica gel was limited
      by the surface diffusion.

PMID- 28496075
TI  - Determination of Fasting and Non-Fasting Cholesterol Levels of Low- and High
      Density Lipoproteins with Homogenous Assays: A Promising Reliable Way to
      Assessment of Dyslipidemia.

PMID- 28496076
TI  - [Early Results of Complex Fractionated Atrial Electrogram Mapping Guided Atrial
      Fibrillation Surgery].
AB  - OBJECTIVE: Although the Cox-maze operation is the standard surgical procedure for
      permanent atrial fibrillation(AF), conversion to sinus rhythm is limited by
      patient characteristics, including the duration of AF, atrial size, and voltage
      of fibrillation waves. A surgical strategy based on structural alteration of the
      electrical substrates of AF is required to achieve better outcomes of AF surgery.
      Complex fractionated atrial electrogram (CFAE) plays an important role in the
      electrical substrate of AF. We performed AF surgery guided by preoperative CFAE
      mapping using a 3-dimensional (3D) mapping system. This study evaluated the early
      results of our procedure. METHODS: From January 2015 to August 2016, 8 patients
      (mean age:66.5+/-6.4 years) underwent CFAE mapping-guided AF surgery. In the
      preoperative electrophysiological study using 3D mapping, CFAE was defined by a
      low voltage electrogram (0.05~0.25 mV) with a highly fractionated potential
      (short cycle length <120 msec). First, right atrial CFAE sites were ablated by
      using a catheter ablation system. Several days after right-sided CFAE ablation, a
      modified Cox-maze operation was performed with additional cryoablation of CFAE
      sites. RESULTS: There were 1~3 (mean:2.5 +/-0.8) CFAE sites in the right atrium
      and 2~4 (mean:2.4+/-0.7) sites in the left atrium. Mean CFAE mapping time was
      87.6+/-24.6 minutes, fluoroscopy time was 53.1+/-22.2 minutes, and volume of
      contrast agent was 44+/-3 ml. Concomitant cardiac surgery included mitral valve
      plasty in 6 patients, and aortic valve replacement and mitral valve replacement
      in 1 patient each. The mean time for CFAE mapping-guided AF surgery was 25.7+/
      5.6 minutes. At discharge, 7 patients were in sinus rhythm and 1 patient still
      had AF, but sinus rhythm recovered at 3 months postoperatively without anti
      arrhythmic medication. After a mean follow-up of 11.7+/-8.5 months, all patients
      remained in sinus rhythm. CONCLUSIONS: Early results suggest that CFAE mapping
      guided atrial fibrillation surgery is feasible and effective. Although the long
      term effect of CFAE ablation on maintenance of sinus rhythm and atrial function
      should be evaluated, this novel method could provide an alternative strategy for
      the surgical treatment of AF.

PMID- 28496077
TI  - [Surgical Training Utilizing Swine Under General Anesthesia and Animal Ethics].
AB  - A cross-sectional study is conducted with primary residents attended wet labs at
      Tohoku University Hospital Advanced Medical Training Center in order to
      investigate the efficacy of the training, especially focused on the animal
      ethics. The 41 participants answered questionnaires in regard to non-technical
      skills, technical skills and ethics before and after the practice. To identify
      differences in each ethical question between 2 time points, Wilcoxon signed ranks
      test was used because the data was not normally distributed. As the result of it,
      all animal ethical questions showed significant differences(0.0016<=p<=0.0380,
      alpha=0.05 level of significance). Beside them, only 1 out of 5 general ethical
      questions showed it (p=0.0137). This outcome verified that the lecture of animal
      ethics and the observation of animal care in this center fixed in the training
      curriculum clearly induced participants' psychological movements.

PMID- 28496078
TI  - [Trial of the Profit Optimization of the Department of Cardiac Surgery in the
      Local National University Hospital].
AB  - In recent years economic sense is required in hospital management, the national
      university hospital is also no exception. We performed duty improvement efforts
      as well as the current state analysis in the department of cardiac surgery for
      the purpose of revenue optimization in our hospital. At result, we succeeded in
      the improvement of the medical index as well as medical profit and found the key
      of solution to the serious problem that national university hospital has.

PMID- 28496079
TI  - [Surgical Treatment for Anomalous Aortic Origin of Coronary Arteries].
AB  - Anomalous aortic origin of coronary arteries is rare. We report 3 cases of
      surgical treatment for anomalous aortic origin of coronary arteries. Case 1 was a
      38-year-old man who was saved by the use of an automated external defibrillator
      from cardiopulmonary arrest while exercising. The coronary angiogram showed the
      right coronary artery arising from the left coronary sinus of Valsalva and being
      located between the aorta and the pulmonary trunk. He underwent coronary artery
      bypass grafting (CABG) using the right internal thoracic artery with ligation of
      proximal part of right coronary artery to prevent sudden death. Case 2 was a 76
      year-old woman with the left coronary artery arising from the right coronary
      sinus of Valsalva and proximal left anterior descending coronary artery stenosis.
      She underwent CABG. Case 3 was a 58-year-old man with severe aortic valve
      regurgitation. He underwent aortic valve replacement. During weaning from
      cardiopulmonary bypass, the electrocardiogram revealed ST-segment elevation.
      Transesophageal echocardiography showed intramural segment of the left coronary
      artery and obstruction of the left coronary blood flow. Repair was accomplished
      by unroofing the intramural segment. All the cases were successfully treated by
      surgical treatment.

PMID- 28496081
TI  - [Salvage Surgery Following Chemoradiotherapy for Thymic Basaloid Cell Carcinoma].
AB  - We performed salvage surgery after chemoradiotherapy(CRT) in a patient with
      thymic basaloid cell carcinoma. A 46-year-old man with an abnormal chest shadow
      on X-ray findings was referred to our hospital. Computed tomography revealed a
      partially solid tumor along with a multilocular cyst in the anterior mediastinum
      with mediastinal lymph node swelling infiltrating to the superior vena cava(SVC).
      Positron emission tomography revealed FDG accumulation (SUVmax 7.94)in the tumor.
      Pathological findings of a tumor biopsy specimen obtained by thoracoscopy led to
      a diagnosis of thymic basaloid cell carcinoma. Following CRT (ADOC+RT:60 Gy), a
      complete resection (R0)with replacement of the SVC was performed. The
      postoperative course was uneventful, and the patient was alive at 20 months after
      surgery with metastasis to the cervical lymph nodes and bone.

PMID- 28496080
TI  - [Surgical Experience of Infective Aneurysm of Brachial Artery Complicated with
      Infective Mitral Valve Endocarditis].
AB  - We report a rare case of aneurysmal formation of the left brachial artery
      complicated with infective endocarditis of the mitral valve. A 67-year-old man
      was referred to our institution for further examination of pulsatile mass at the
      left upper extremity. Computed tomography showed a left brachial arterial
      aneurysm with a diameter of 4 cm and gradual expansion of the aneurysm was also
      recognized. Furthermore, echocardiography revealed severe mitral valve
      regurgitation with a vegetation. There was no feature of congestive heart
      failure. He was diagnosed with subacute infective endocarditis and infective left
      brachial arterial aneurysm. Considering these clinical findings, staged surgical
      treatment was planned. He underwent resection of the brachial arterial aneurysm
      and bypass grafting with an autologous saphenous vein on an urgent basis. One
      month after the initial operation, elective mitral valve plasty was successfully
      performed. Although aneurysmal formation of the brachial artery subsequent to
      infective endocarditis is rare, we should keep this potentially serious
      complication in mind.

PMID- 28496083
TI  - [Retrograde Type A Aortic Dissection after Thoracic Endovascular Aortic
      Repair;Report of a Case].
AB  - A 72-year-old man presented with aneurysms of the distal aortic arch and the
      distal descending aorta due to chronic type B aortic dissection. We first
      performed thoracic endovascular aortic repair (TEVAR) in the distal descending
      aorta, and the aneurysm was successfully excluded using a Gore Tag stentgraft.
      Seven days after TEVAR, computed tomography revealed retrograde type A aortic
      dissection occurring from the ascending aorta to the distal aortic arch. In
      emergency surgery, ascending aorta and total arch replacement were performed
      under selective cerebral perfusion with moderate hypothermia, and after coming
      off cardiopulmonary bypass, the distal aortic arch aneurysm was excluded using a
      Gore Tag stentgraft.

PMID- 28496082
TI  - [Slowly progressive Basaloid Squamous Cell Carcinoma of the Lung].
AB  - Basaloid squamous cell carcinoma (BSC) of the lung is a rare variant of squamous
      cell carcinoma (SCC) and is reported to show poor prognosis. A 70-year-old man
      presented to the clinic complaining of a productive cough. Computed tomography(
      CT) of the chest revealed a nodule in the left lower lobe of the lung. A
      bronchoscopy and transbronchial lung biopsy(TBB) were performed twice;no evidence
      of malignancy was found. So we followed up by periodic chest CT. One year and 4
      months after the 1st visit, the nodule increased in size from 14 to 19 mm. TBB
      was performed again and the tumor was diagnosed as SCC. The patient underwent a
      left lower lobectomy and the tumor was diagnosed as BSC by postoperative
      pathological examination. Two years and 6 months after surgery, no recurrence has
      been observed in the patient.

PMID- 28496084
TI  - [Redissection of the Aortic Root Three Months after Replacement of the Ascending
      Aorta for Acute Stanford Type A Dissection;Report of a Case].
AB  - We report a case of redissection of the aortic root after graft replacement for
      acute aortic dissection using BioGlue to approximate the false lumen. A 49-year
      old man underwent graft replacement of the ascending aorta for acute aortic
      dissection. In this operation, BioGlue was applied to the false lumen of the
      aortic root. Three months later, computed tomography revealed an ulcer-like
      projection and an intramural hematoma in the aortic root. Aortic root replacement
      was performed, in which operative findings showed a new intimal tear and a patent
      false lumen contained with hematomas and a fragment of BioGlue. Histological
      examination showed no evidence of adhesion between the intimal media and the
      adventitia of the aorta, or toxic effect of BioGlue. We conclude that care should
      be taken in applying the BioGlue to a false lumen and that cautious follow-up is
      mandatory not to overlook redissection.

PMID- 28496085
TI  - [Graft Pseudoaneurysm after Ascending to Abdominal Aorta Bypass for Atypical
      Coarctation Due to Aortitis Syndrome;Report of a Case].
AB  - We present a case of a 44-year-old woman, with pseudoaneurysm formation at the
      middle of the prosthetic graft, 60 mm in diameter. She had been diagnosed with
      atypical coarctation due to aortitis 27 years before, and had undergone a bypass
      operation with 14 mm-diameter Cooley double velour graft from the ascending aorta
      to the abdominal aorta. This time, endovascular aortic repair was performed to
      prevent rupture of the pseudoaneurysm. Though a knitted Dacron graft has a risk
      of psuedaneurysm formation long patency could be obtained when used in ascending
      aorta-abdominal aorta bypass.

PMID- 28496086
TI  - [Surgical Treatment of Left Main Trunk Coronary Artery Aneurysm with Asymptomatic
      Myocardial Ischemia;Report of a Case].
AB  - Coronary artery aneurysm is rare, and there is no established protocol for
      surgical indication. On preoperative examination of orthopedic surgery, a 76-year
      old male was found with asymptomatic myocardial ischemia. Radiological
      examinations revealed triple vessel disease and a coronary artery aneurysm, 10 mm
      in size, at the bifurcation of the left main trunk. Combined with quintuple
      coronary artery bypass grafting, surgical repair of the aneurysm was peformed
      under cardiopulmonary bypass on beating heart. Epicardial echocardiography was
      used to detect the site and the blood flow on the aneurysm. Postoperative course
      was uneventful. Epicardial echocardiography was useful for detecting the coronary
      artery aneurysm in the myocardium and the residual aneurysmal blood flow.

PMID- 28496087
TI  - [Rupture of an Aneurysm of the Right Sinus of Valsalva Into the
      Pericardium;Report of a Case].
AB  - A sinus of Valsalva aneurysm is an uncommon cardiac anomaly. The aneurysm usually
      ruptures into the cardiac cavity, and rupture into the pericardial cavity is
      unusual. A 69-year-old man was admitted to our hospital after collapse due to
      cardiac tamponade. Computed tomography revealed a ruptured right sinus of
      Valsalva aneurysm (5 cm) with massive pericardial effusion. The right coronary
      artery arose from the aneurysm. Severe aortic regurgitation due to the lack of
      coaptation of the valves was detected by echocardiography. Emergency patch
      closure of the aneurysm orifice, aortic valve replacement, and coronary artery
      bypass grafting to the right coronary artery were performed. The postoperative
      course was uneventful and the patient was discharged on postoperative day 28 in
      good health.

PMID- 28496088
TI  - [Lung Abscess with Acute Empyema Which Improved after Performing by Video
      Assissted Thoracic Surgery( Including Pneumonotomy and Lung Abscess
      Drainage);Report of a Case].
AB  - We herein report the case of a patient demonstrating a lung abscess with acute
      empyema which improved after performing pnemumonotomy and lung abscess drainage.
      A 60-year-old male was referred to our hospital to receive treatment for a lung
      abscess with acute empyema. At surgery, the lung parenchyma was slightly torn
      with pus leakage. After drainage of lung abscess by enlarging the injured part,
      curettage in the thoracic cavity and decortication were performed. The
      postoperative course was uneventful. Direct drainage of an abscess into the
      thoracic cavity is thought to be a choice for the treatment of lung abscesses.

PMID- 28496089
TI  - [Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully
      Treated by Intrapleural Administration of Diluted Fibrin Glue;Report of a Case].
AB  - Malignant pleural mesothelioma sometimes accompanies intractable neumothorax due
      to the visceral pleural invasion of the tumor. A 68-years-old man was found to
      have massive pleural effusion and pleural mass combined with pneumothorax by
      computed tomography(CT). CT guided biopsy revealed the mass to be malignant
      pleural mesothelioma. Since continuous air leakage was observed by chest
      drainage, pleurodesis by OK-432 twice and bronchial occlusion by Endobronchial
      Watanabe Spigot (EWS)were performed. But air leakage continued, and the surgery
      was performed, however the treatment failed to stop the air leakage. Finally, the
      intrapleural administration of diluted fibrin glue was challenged and the air
      leakage stopped immediately after the treatment.

PMID- 28496090
TI  - [Mediastinal Thyroid Carcinoma;Report of a Case].
AB  - 71-year-old woman was pointed out to have an asymptomatic mediastinal tumor.
      Chest computed tomography(CT) showed a well-demarcated mass measuring 7 cm in
      diameter in the anterior mediastinum. We resected the mass through a median
      sternotomy. The tumor had a clear margin without invasion to the surrounding
      tissue and did not show continuity with the cervical thyroid gland.
      Histopathologically, the tumor was diagnosed as follicular thyroid carcinoma with
      capsular invasion. This is an exceptionally rare case.

PMID- 28496091
TI  - Mobilization of Hematopoietic Stem Cells for Hematopoietic Cells Autologous
      Transplantation with Use of Plerixafor.
AB  - BACKGROUND To increase the number of circulating hematopoietic stem cells (HSC)
      in the blood, mobilization treatments are currently being used. G-CSF and G-CSF
      plus chemotherapy are the most common methods of hematopoietic stem cells
      separation used in Poland. MATERIAL AND METHODS We observed patients who failed
      an effective hematopoietic stem cell mobilization with G-CSF or with G-CSF plus
      chemotherapy. The separation was considered unsuccessful if within a period of 4
      consecutive days of separation, the number of obtained CD 34+ cells was lower
      than 2.0*10^6/kg of bodyweight. The study involved 32 patients whose CD34+ cells
      were collected and the collection for autologous transplantation failed. The
      study included 20 men and 12 women. Among all 32 patients, 28 had multiple
      myeloma, 3 had DLBCL lymphoma, and 1 had Hodgkin's disease. RESULTS Separation
      was unsuccessful in only 3 patients; the remaining 29 achieved an average of
      4.83*10^6 CD34+ cells per kg of bodyweight. We conclude that plerixafor is an
      important tool in obtaining sufficient quantities of cells for hematopoietic stem
      cells separation. CONCLUSIONS The use of plerixafor is a sufficient and safe
      option for stem cells mobilization in autologous transplantations.

PMID- 28496092
TI  - Usefulness of Contrast-Enhanced Ultrasonography for Predicting Esophageal Varices
      in Patients with Hepatitis B Virus (HBV)-Related Cirrhosis.
AB  - BACKGROUND The aim of this study was to investigate the usefulness of contrast
      enhanced ultrasonography (CEUS) in predicting of esophageal varices (EV) and
      assessing high-risk EV in patients with hepatitis B virus (HBV)-related
      cirrhosis. MATERIAL AND METHODS Patients with HBV-related cirrhosis who had
      undergone endoscopy were prospectively recruited. Hepatic dynamic CEUS was
      performed. Regions of interest (ROI) were drawn on the hepatic artery, hepatic
      vein, portal vein, and liver parenchyma to measure the corresponding features,
      such as arrival times. Spearman's correlation analysis was used to determine the
      relations between several dynamic CEUS features and the degree of EV. Receiver
      operating characteristics (ROC) curves were constructed to investigate the
      diagnostic performance of CEUS in assessing the presence of EV and high-risk EV.
      RESULTS Fifty-eight patients (44 men; mean age 51.3 years) were included in this
      study. Of these, 18 (31.0%), 12 (20.7%), 11 (19.0%), and 17 (29.3%) of patients
      had grade 0, 1, 2, and 3 EV, respectively. Grade 2 and grade 3 EV were considered
      high-risk EV. Among the CEUS features, the area under the ROC curves of
      intrahepatic transit time (HV-HA, i.e., the difference between hepatic vein
      arrival time and hepatic artery arrival time) both for assessment of the presence
      of EV and high-risk EV (0.883 and 0.915, respectively) were larger than the other
      indices. HV-HA was negatively correlated with the grade of EV. An HV-HA of under
      8.2 s indicated the presence of EV and under 7 s indicated high-risk EV.
      CONCLUSIONS Dynamic CEUS imaging is useful in assessing the presence of EV and
      high-risk EV in patients with HBV-related cirrhosis.

PMID- 28496094
TI  - Apical Hypertrophic Cardiomyopathy: Case Report and Literature Review.
AB  - BACKGROUND Apical hypertrophic cardiomyopathy (ApHCM) is a relatively rare form
      of hypertrophic cardiomyopathy that predominantly affects the apex of the left
      ventricle and typically has a nonobstructive physiology. Its variable
      presentation and clinical course render ApHCM a commonly delayed or missed
      diagnosis. CASE REPORT A 53-year-old Caucasian woman presented with chronic
      progressive chest pain. She was initially started on treatment for acute coronary
      syndrome. Diagnosis of ApHCM was initially missed on echocardiography, but made
      on subsequent cardiac catheterization and cardiac MRI. She improved clinically
      with metoprolol, had a work-up for implantable cardioverter-defibrillator
      placement, and was referred for genetic testing. CONCLUSIONS Despite earlier
      studies suggesting a more benign clinical course of ApHCM, recent studies report
      increased morbidity and mortality, which is comparable to the prognosis of other
      variants of hypertrophic cardiomyopathy such as hypertrophic obstructive
      cardiomyopathy. Thus, when formulating a differential diagnosis for chest pain,
      it is important to include structural heart disease including apical and other
      variants of hypertrophic cardiomyopathy as part of that differential, as
      appropriate management can prevent these devastating sequelae. Furthermore, when
      screening tests such as echocardiography cannot adequately establish the
      diagnosis of ApHCM, then cardiac MRI or invasive hemodynamic testing is necessary
      to establish or refute the diagnosis.

PMID- 28496093
TI  - Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count
      Tests: A Comprehensive Systematic Review with Meta-Analysis.
AB  - BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent
      arrhythmias precipitating morbidities and mortalities. The complete blood count
      (CBC) test is an important blood test in clinical practice and is routinely used
      in the workup of cardiovascular diseases. This systematic review with meta
      analysis aimed to determine the strength of evidence for evaluating the
      association of hematological parameters in the CBC test with new-onset and
      recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational
      studies evaluating hematologic parameters in patients with new-onset AF and
      recurrent AF. A comprehensive subgroup analysis was performed to explore
      potential sources of heterogeneity. RESULTS The literature search of all major
      databases retrieved 2150 studies. After screening, 70 studies were analyzed in
      the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis
      on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of
      -26.39*10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001),
      white blood cell (WBC) (WMD=-0.005*10^9/L and p=0.83), neutrophil to lymphocyte
      ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW)
      (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF
      revealed PC (WMD=-2.71*109/L and p=0.59), WBC (WMD=0.20*10^9/L (95% CI: 0.08 to
      0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001).
      CONCLUSIONS Hematological parameters have significant ability to predict
      occurrence and recurrence of AF. Therefore, emphasizing the potential predictive
      role of hematological parameters for new-onset and recurrent AF, we recommend
      adding the CBC test to the diagnostic modalities of AF in clinical practice.

PMID- 28496096
TI  - Direct atomic scale determination of magnetic ion partition in a room temperature
      multiferroic material.
AB  - The five-layer Aurivillius phase Bi6TixFeyMnzO18 system is a rare example of a
      single-phase room temperature multiferroic material. To optimise its properties
      and exploit it for future memory storage applications, it is necessary to
      understand the origin of the room temperature magnetisation. In this work we use
      high resolution scanning transmission electron microscopy, EDX and EELS to
      discover how closely-packed Ti/Mn/Fe cations of similar atomic number are
      arranged, both within the perfect structure and within defect regions. Direct
      evidence for partitioning of the magnetic cations (Mn and Fe) to the central
      three of the five perovskite (PK) layers is presented, which reveals a marked
      preference for Mn to partition to the central layer. We infer this is most
      probably due to elastic strain energy considerations. The observed increase (>8%)
      in magnetic cation content at the central PK layers engenders up to a 90%
      increase in potential ferromagnetic spin alignments in the central layer and this
      could be significant in terms of creating pathways to the long-range room
      temperature magnetic order observed in this distinct and intriguing material
      system.

PMID- 28496095
TI  - Duration of motherhood has incremental effects on mothers' neural processing of
      infant vocal cues: a neuroimaging study of women.
AB  - The transition to motherhood, and the resultant experience of caregiving, may
      change the way women respond to affective, infant signals in their environments.
      Nonhuman animal studies have robustly demonstrated that mothers process both
      infant and other salient signals differently from nonmothers. Here, we
      investigated how women with and without young infants respond to vocalisations
      from infants and adults (both crying and neutral). We examined mothers with
      infants ranging in age (1-14 months) to examine the effects of duration of
      maternal experience. Using functional magnetic resonance imaging, we found that
      mothers showed greater activity than nonmothers to vocalisations from adults or
      infants in a range of cortical regions implicated in the processing of affective
      auditory cues. This main effect of maternal status suggests a general difference
      in vocalisation processing across infant and adult sounds. We found that a longer
      duration of motherhood, and therefore more experience with an infant, was
      associated with greater infant-specific activity in key parental brain regions,
      including the orbitofrontal cortex and amygdala. We suggest that these
      incremental differences in neural activity in the maternal brain reflect the
      building of parental capacity over time. This is consistent with
      conceptualizations of caregiving as a dynamic, learning process in humans.

PMID- 28496097
TI  - Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to
      Repress Interferon Action.
AB  - Hepatitis B virus (HBV) infection causes acute hepatitis B (AHB), chronic
      hepatitis B (CHB), liver cirrhosis (LC), and eventually hepatocellular carcinoma
      (HCC). The presence of hepatitis B e antigen (HBeAg) in the serum generally
      indicates ongoing viral replication and disease progression. However, the
      mechanism by which HBeAg regulates HBV infection remains unclear. Interferons
      (IFNs) are pleiotropic cytokines that participate in host innate immunity. After
      binding to receptors, IFNs activate the JAK/STAT pathway to stimulate expression
      of IFN-stimulated genes (ISGs), leading to induction of antiviral responses.
      Here, we revealed that HBeAg represses IFN/JAK/STAT signaling to facilitate HBV
      replication. Initially, HBeAg stimulates the expression of suppressor of cytokine
      signaling 2 (SOCS2). Subsequently, SOCS2 impairs IFN/JAK/STAT signaling through
      reducing the stability of tyrosine kinase 2 (TYK2), downregulating the expression
      of type I and III IFN receptors, attenuating the phosphorylation and nucleus
      translocation of STAT1. Finally, SOCS2 inhibits the expression of ISGs, which
      leads to the repression of IFN action and facilitation of viral replication.
      These results demonstrate an important role of HBeAg in the regulation of IFN
      action, and provide a possible molecular mechanism by which HBV resists the IFN
      therapy and maintains persistent infection.

PMID- 28496098
TI  - Combined treatment with Metformin and 2-deoxy glucose induces detachment of
      viable MDA-MB-231 breast cancer cells in vitro.
AB  - Triple naegative breast cancer has an increased rate of distant metastasis and
      consequently poor prognosis. To metastasize, breast cancer cells must detach from
      the main tumour mass and resist anoikis, a programmed cell death induced by lack
      of cell-extracellular matrix communication. Although cancer cells must detach to
      metastasize in vivo, the viability of floating cancer cells in vitro is rarely
      investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231
      cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of
      floating cells, of which about 95% were viable. Floating cells resumed their
      proliferation once they were reseeded in the pharmacological compound-free
      medium. Similar effects on detachment were observed on anoikis-prone MCF-7 cells.
      Co-treatment of MDA-MB-231 cells with metformin and 2-DG induced a strong
      activation of AMP-activated protein kinase (AMPK), which was reduced by AMPK
      inhibitor compound C that prevented detachment of MDA-MB-231 cells. However,
      direct AMPK activators A-769662 and AICAR did not have any major effect on the
      percentage of floating MDA-MB-231 cells, indicating that AMPK activation is
      necessary but not sufficient for triggering detachment of cancer cells. Our
      results demonstrate that separate analysis of floating and attached cancer cells
      might be important for evaluation of anti-cancer agents.

PMID- 28496099
TI  - Reentrant Resistive Behavior and Dimensional Crossover in Disordered
      Superconducting TiN Films.
AB  - A reentrant temperature dependence of the normal state resistance often referred
      to as the N-shaped temperature dependence, is omnipresent in disordered
      superconductors - ranging from high-temperature cuprates to ultrathin
      superconducting films - that experience superconductor-to-insulator transition.
      Yet, despite the ubiquity of this phenomenon its origin still remains a subject
      of debate. Here we investigate strongly disordered superconducting TiN films and
      demonstrate universality of the reentrant behavior. We offer a quantitative
      description of the N-shaped resistance curve. We show that upon cooling down the
      resistance first decreases linearly with temperature and then passes through the
      minimum that marks the 3D-2D crossover in the system. In the 2D temperature range
      the resistance first grows with decreasing temperature due to quantum
      contributions and eventually drops to zero as the system falls into a
      superconducting state. Our findings demonstrate the prime importance of disorder
      in dimensional crossover effects.

PMID- 28496100
TI  - Structure and function of a broad-specificity chitin deacetylase from Aspergillus
      nidulans FGSC A4.
AB  - Enzymatic conversion of chitin, a beta-1,4 linked polymer of N-acetylglucosamine,
      is of major interest in areas varying from the biorefining of chitin-rich waste
      streams to understanding how medically relevant fungi remodel their chitin
      containing cell walls. Although numerous chitinolytic enzymes have been studied
      in detail, relatively little is known about enzymes capable of deacetylating
      chitin. We describe the structural and functional characterization of a 237
      residue deacetylase (AnCDA) from Aspergillus nidulans FGSC A4. AnCDA acts on
      chito-oligomers, crystalline chitin, chitosan, and acetylxylan, but not on
      peptidoglycan. The K m and k cat of AnCDA for the first deacetylation of penta-N
      acetyl-chitopentaose are 72 uM and 1.4 s-1, respectively. Combining mass
      spectrometry and analyses of acetate release, it was shown that AnCDA catalyses
      mono-deacetylation of (GlcNAc)2 and full deacetylation of (GlcNAc)3-6 in a non
      processive manner. Deacetylation of the reducing end sugar was much slower than
      deacetylation of the other sugars in chito-oligomers. These enzymatic
      characteristics are discussed in the light of the crystal structure of AnCDA,
      providing insight into how the chitin deacetylase may interact with its
      substrates. Interestingly, AnCDA activity on crystalline chitin was enhanced by a
      lytic polysaccharide monooxygenase that increases substrate accessibility by
      oxidative cleavage of the chitin chains.

PMID- 28496101
TI  - Stretchable, Twisted Conductive Microtubules for Wearable Computing, Robotics,
      Electronics, and Healthcare.
AB  - Stretchable and flexible multifunctional electronic components, including sensors
      and actuators, have received increasing attention in robotics, electronics,
      wearable, and healthcare applications. Despite advances, it has remained
      challenging to design analogs of many electronic components to be highly
      stretchable, to be efficient to fabricate, and to provide control over electronic
      performance. Here, we describe highly elastic sensors and interconnects formed
      from thin, twisted conductive microtubules. These devices consist of twisted
      assemblies of thin, highly stretchable (>400%) elastomer tubules filled with
      liquid conductor (eutectic gallium indium, EGaIn), and fabricated using a simple
      roller coating process. As we demonstrate, these devices can operate as
      multimodal sensors for strain, rotation, contact force, or contact location. We
      also show that, through twisting, it is possible to control their mechanical
      performance and electronic sensitivity. In extensive experiments, we have
      evaluated the capabilities of these devices, and have prototyped an array of
      applications in several domains of stretchable and wearable electronics. These
      devices provide a novel, low cost solution for high performance stretchable
      electronics with broad applications in industry, healthcare, and consumer
      electronics, to emerging product categories of high potential economic and
      societal significance.

PMID- 28496102
TI  - Partial microduplication in the histone acetyltransferase complex member KANSL1
      is associated with congenital heart defects in 22q11.2 microdeletion syndrome
      patients.
AB  - 22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion
      disorder in humans, with an incidence of 1/4000 live births. It is caused by a
      heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the
      deletion present features that include neuropsychiatric problems, craniofacial
      abnormalities and cardiovascular malformations. However, the phenotype is highly
      variable and the factors related to the clinical heterogeneity are not fully
      understood. About 65% of patients with 22q11.2DS have congenital heart defects
      (CHD). The main goal of this study was to identify common CNVs in 22q11.2DS
      patients that could be associated with the incomplete penetrance of CHD. Analysis
      of genomic DNA from 253 patients with 22q11.2DS using array technology showed an
      association between a microduplication located in region 17q21.31 and CHD (p
      value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first
      three exons of KANSL1 gene. Bioinformatic analysis showed that KANSL1 and CRKL, a
      gene in the commonly deleted region of 22q11.2DS, are part of the same regulatory
      module in a miRNA-mRNA network. These results show that a KANSL1
      microduplication, in combination with the 22q11.2 deletion, is associated with
      increased risk of CHD in these patients, suggesting that KANSL1 plays a role as a
      modifier gene in 22q11.2DS patients.

PMID- 28496103
TI  - In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for
      in vivo bone regeneration applications.
AB  - Bioprinting has emerged as a novel technological approach with the potential to
      address unsolved questions in the field of tissue engineering. We have recently
      shown that Laser Assisted Bioprinting (LAB), due to its unprecedented cell
      printing resolution and precision, is an attractive tool for the in situ printing
      of a bone substitute. Here, we show that LAB can be used for the in situ printing
      of mesenchymal stromal cells, associated with collagen and nano-hydroxyapatite,
      in order to favor bone regeneration, in a calvaria defect model in mice. Also, by
      testing different cell printing geometries, we show that different cellular
      arrangements impact on bone tissue regeneration. This work opens new avenues on
      the development of novel strategies, using in situ bioprinting, for the building
      of tissues, from the ground up.

PMID- 28496104
TI  - Gender Differences in Bile Acids and Microbiota in Relationship with Gender
      Dissimilarity in Steatosis Induced by Diet and FXR Inactivation.
AB  - This study aims to uncover how specific bacteria and bile acids (BAs) contribute
      to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both
      genders. A control diet (CD) and Western diet (WD), which contains high fat and
      carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice
      followed by phenotyping characterization as well as BA and microbiota profiling.
      Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and
      highest hepatic and serum lipids as well as insulin resistance among the eight
      studied groups. Gender differences in WD-induced steatosis, insulin sensitivity,
      and predicted microbiota functions were all FXR-dependent. FXR deficiency
      enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which
      were accompanied by increased hepatic taurine-conjugated cholic acid and beta
      muricholic acid as well as hepatic and serum lipids. Additionally, distinct
      microbiota profiles were found in WD-fed WT mice harboring simple steatosis and
      CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver
      cancer. Together, the presented data revealed FXR-dependent concomitant
      relationships between gut microbiota, BAs, and metabolic diseases in both
      genders. Gender differences in BAs and microbiota may account for gender
      dissimilarity in metabolism and metabolic diseases.

PMID- 28496105
TI  - Off-Stoichiometry Driven Carrier Density Variation at the Interface of
      LaAlO3/SrTiO3.
AB  - The interface between LaAlO3 (LAO) and SrTiO3 (STO) has attracted enormous
      interests due to its rich physical phenomena, such as metallic nature, magnetism
      and superconductivity. In this work, we report our experimental investigations on
      the influence of the LAO stoichiometry to the metallic interface. Taking
      advantage of the oxide molecular beam epitaxy (MBE) technique, a series of high
      quality LAO films with different nominal La/Al ratios and LAO thicknesses were
      grown on the TiO2-terminated STO substrates, where systematic variations of the
      LAO lattice constant and transport property were observed. In particular, the
      sheet density can be largely reduced by nearly an order of magnitude with merely
      about 20% increase in the nominal La/Al ratio. Our finding provides an effective
      method on tuning the electron density of the two-dimensional electron liquid
      (2DEL) at the LAO/STO interface.

PMID- 28496106
TI  - Neuregulin 1 improves complex 2-mediated mitochondrial respiration in skeletal
      muscle of healthy and diabetic mice.
AB  - It has been reported that neuregulin1 (NRG1) improves glucose tolerance in
      healthy and diabetic rodents. In vitro studies also suggest that NRG1 regulates
      myocyte oxidative capacity. To confirm this observation in vivo, we evaluated the
      effect on mitochondrial function of an 8-week treatment with NRG1 in db/db
      diabetic mice and C57BL/6JRJ healthy controls. NRG1 treatment improved complex 2
      mediated mitochondrial respiration in the gastrocnemius of both control and
      diabetic mice and increased mitochondrial complex 2 subunit content by 2-fold.
      This effect was not associated with an increase in mitochondrial biogenesis
      markers. Enhanced ERBB4 phosphorylation could mediate NRG1 effects on
      mitochondrial function through signalling pathways, independently of ERK1/2, AKT
      or AMPK.

PMID- 28496107
TI  - CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via
      interleukin-10 and PD-L1 production in oral squamous cell carcinoma.
AB  - Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion,
      and metastasis by producing various mediators. Although preclinical studies
      demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in
      oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined
      the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were
      analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We
      examined TAM subsets and their production of immune suppressive molecules (IL-10
      and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow
      cytometry. CD163 was detected around the tumor or connective tissue, while CD204
      was detected in/around the tumors. Flow cytometric analysis revealed that
      CD163+CD204+ TAMs strongly produced IL-10 and PD-L1 in comparison with
      CD163+CD204- and CD163-CD204+ TAMs. Furthermore, the number of activated CD3+ T
      cells after co-culture with CD163+CD204+ TAMs was significantly lower than that
      after co-culture with other TAM subsets. In clinical findings, the number of
      CD163+CD204+ TAMs was negatively correlated with that of CD25+ cells and 5-year
      progression-free survival. These results suggest that CD163+CD204+ TAMs possibly
      play a key role in the invasion and metastasis of OSCC by T-cell regulation via
      IL-10 and PD-L1 production.

PMID- 28496108
TI  - Alpha7 nicotinic acetylcholine receptor agonist promotes retinal ganglion cell
      function via modulating GABAergic presynaptic activity in a chronic glaucomatous
      model.
AB  - Alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) agonists can prevent
      glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs).
      However, the neuroprotective effects and the mechanism of action of PNU-282987,
      an alpha7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly
      understood. We found that elevated intraocular pressure (IOP) downregulated
      retinal alpha7-nAChR expression. Electroretinography revealed that the amplitude
      of the photopic negative response (PhNR) decreased in parallel with the loss of
      RGCs caused by elevated IOP. PNU-282987 enhanced RGC viability and function and
      decreased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      positive signals in RGCs. Patch-clamp recordings revealed differences in the
      baseline frequencies and decay times of the miniature GABAergic inhibitory
      postsynaptic currents (mIPSCs) of RGCs between control and glaucomatous retinal
      slices. The results of western blotting and immunostaining showed that glutamic
      acid decarboxylase 65/67 and GABA deficits persisted in glaucomatous retinas and
      that these deficits were reversed by PNU-282987. Patch-clamp recordings also
      showed that PNU-282987 significantly increased the frequency and amplitude of the
      GABAergic mIPSCs of RGCs. The protective effects of PNU-292987 were blocked by
      intravitreal administration of selective GABAA receptor antagonists. The
      modulation of GABAergic synaptic transmission by PNU-282987 causes de-excitation
      of ganglion cell circuits and suppresses excitotoxic processes.

PMID- 28496109
TI  - The quantum Zeno and anti-Zeno effects with strong system-environment coupling.
AB  - To date, studies of the quantum Zeno and anti-Zeno effects focus on quantum
      systems that are weakly interacting with their environment. In this paper, we
      investigate what happens to a quantum system under the action of repeated
      measurements if the quantum system is strongly interacting with its environment.
      We consider as the quantum system a single two-level system coupled strongly to a
      collection of harmonic oscillators. A so-called polaron transformation is then
      used to make the problem in the strong system-environment coupling regime
      tractable. We find that the strong coupling case exhibits quantitative and
      qualitative differences as compared with the weak coupling case. In particular,
      the effective decay rate does not depend linearly on the spectral density of the
      environment. This then means that, in the strong coupling regime that we
      investigate, increasing the system-environment coupling strength can actually
      decrease the effective decay rate. We also consider a collection of two-level
      atoms coupled strongly with a common environment. In this case, we find that
      there are further differences between the weak and strong coupling cases since
      the two-level atoms can now indirectly interact with one another due to the
      common environment.

PMID- 28496110
TI  - The association between psychological stress and miscarriage: A systematic review
      and meta-analysis.
AB  - This systematic review and meta-analysis was designed to investigate whether
      maternal psychological stress and recent life events are associated with an
      increased risk of miscarriage. A literature search was conducted to identify
      studies reporting miscarriage in women with and without history of exposure to
      psychological stress (the only exposure considered). The search produced 1978
      studies; 8 studies were suitable for analysis. A meta-analysis was performed
      using a random-effects model with effect sizes weighted by the sampling variance.
      The risk of miscarriage was significantly higher in women with a history of
      exposure to psychological stress (OR 1.42, 95% CI 1.19-1.70). These findings
      remained after controlling for study type (cohort and nested case-control study
      OR 1.33 95% CI 1.14-1.54), exposure types (work stress OR 1.27, 95% CI 1.10
      1.47), types of controls included (live birth OR 2.82 95% CI: 1.64-4.86). We
      found no evidence that publication bias or study heterogeneity significantly
      influenced the results. Our finding provides the most robust evidence to date,
      that prior psychological stress is harmful to women in early pregnancy.

PMID- 28496111
TI  - Indirect meta-analysis comparing clinical outcomes of total cervical disc
      replacements with fusions for cervical degenerative disc disease.
AB  - Anterior cervical discectomy and fusion (ACDF) and total cervical disc
      replacement (TDR) are considered effective treatments for patients with cervical
      degenerative disc disease (CDDD). An indirect meta-analysis including 19
      randomized controlled trials (5343 patients) was conducted to compare the
      clinical outcomes of ACDF with TDR. Primary outcomes including functional
      indicators (NDI [neck disability index] score, neurological success and patient
      satisfaction), secondary outcomes including surgical outcomes (operation time,
      blood loss and length of stay) and secondary surgical procedures (secondary
      surgery at an adjacent level, secondary surgery at the index level, secondary
      surgery at both levels, removal, reoperation, revision and supplemental fixation)
      were included in the study. TDR using the Bryan disc was associated with a
      greater improvement in NDI score than ACDF (MD = -5.574, 95% CrIs [credible
      intervals] -11.73--0.219). For neurological success, the Bryan (odds ratio [OR] =
      0.559, 95% CrIs 0.323-0.955) and Prestige (OR = 0.474, 95% CrIs 0.319-0.700)
      discs were superior to ACDF. However, no differences in the patient satisfaction
      rate were shown between TDR and ACDF. For patients with CDDD, ACDF using
      allograft and a plate is most effective for determining the surgical parameters.
      Moreover, TDR using the ProDisc-C, Mobi-C, Prestige and Bryan discs are good
      choices for improving functional outcomes and reducing secondary surgeries.

PMID- 28496112
TI  - "TORNADO" - Theranostic One-Step RNA Detector; microfluidic disc for the direct
      detection of microRNA-134 in plasma and cerebrospinal fluid.
AB  - Diagnosis of seizure disorders such as epilepsy currently relies on clinical
      examination and electroencephalogram recordings and is associated with
      substantial mis-diagnosis. The miRNA, miR-134 (MIR134 in humans), has been found
      to be elevated in brain tissue after experimental status epilepticus and in human
      epilepsy cells and their detection in biofluids may serve as unique biomarkers.
      miRNAs from unprocessed human plasma and human cerebrospinal fluid samples were
      used in a novel electrochemical detection based on electrocatalytic platinum
      nanoparticles inside a centrifugal microfluidic device where the sandwich assay
      is formed using an event triggered release system, suitable for the rapid point
      of-care detection of low abundance biomarkers of disease. The device has the
      advantage of controlling the rotation speed of the centrifugal device to pump
      nanoliter volumes of fluid at a set time and manipulate the transfer of liquids
      within the device. The centrifugal platform improves reaction rates and yields by
      proposing efficient mixing strategies to overcome diffusion-limited processes and
      improve mass transport rates, resulting in reduced hybridization times with a
      limit of detection of 1 pM target concentration. Plasma and cerebrospinal fluid
      samples (unprocessed) from patients with epilepsy or who experienced status
      epilepticus were tested and the catalytic response obtained was in range of the
      calibration plot. This study demonstrates a rapid and simple detection for
      epilepsy biomarkers in biofluid.

PMID- 28496113
TI  - The Beneficial Role of Mobility for the Emergence of Innovation.
AB  - Innovation is a key ingredient for the evolution of several systems, including
      social and biological ones. Focused investigations and lateral thinking may lead
      to innovation, as well as serendipity and other random discovery processes. Some
      individuals are talented at proposing innovation (say innovators), while others
      at deeply exploring proposed novelties, at getting further insights on a theory,
      or at developing products, services, and so on (say developers). This separation
      in terms of innovators and developers raises an issue of paramount importance:
      under which conditions a system is able to maintain innovators? According to a
      simple model, this work investigates the evolutionary dynamics that characterize
      the emergence of innovation. In particular, we consider a population of
      innovators and developers, in which agents form small groups whose composition is
      crucial for their payoff. The latter depends on the heterogeneity of the formed
      groups, on the amount of innovators they include, and on an award-factor that
      represents the policy of the system for promoting innovation. Under the
      hypothesis that a "mobility" effect may support the emergence of innovation, we
      compare the equilibria reached by our population in different cases. Results
      confirm the beneficial role of "mobility", and the emergence of further
      interesting phenomena.

PMID- 28496115
TI  - Erratum: A two-qubit photonic quantum processor and its application to solving
      systems of linear equations.

PMID- 28496114
TI  - New quaternary half-metallic ferromagnets with large Curie temperatures.
AB  - New magnetic materials with high Curie temperatures for spintronic applications
      are perpetually sought for. In this paper, we present an ab initio study of the
      structural, electronic and magnetic properties of Quaternary Heusler compounds
      CoX'Y'Si where X' is a transition metal with 4d electrons and Y' is either Fe or
      Mn. We find five new half-metallic ferromagnets with spin polarisation nearly
      100% with very high Curie temperatures. The variation of Curie temperatures as a
      function of valence electrons can be understood from the calculated inter-atomic
      exchange interaction parameters. We also identify a few other compounds, which
      could be potential half-metals with suitable application of pressure or with
      controlled doping. Our results reveal that the half-metallicity in these
      compounds is intricately related to the arrangements of the magnetic atoms in the
      Heusler lattice and hence, the interatomic exchange interactions between the
      moments. The trends in the atomic arrangements, total and local magnetic moments,
      interatomic magnetic exchange interactions and Curie temperatures are discussed
      with fundamental insights.

PMID- 28496116
TI  - Antinociceptive effects of caloric restriction on post-incisional pain in
      nonobese rats.
AB  - Caloric restriction (CR) increases lifespan, retards physiological signs of
      aging, and delays a variety of diseases. Reduction of inflammatory response was
      proposed as one of the molecular mechanisms for how CR exerts beneficial effects.
      The present study investigated the effects of CR on postoperative pain in rats.
      Adult nonobese rats were divided into two dietary groups, an ad libitum fed group
      (AL) and a caloric restriction group (CR) that was provided with 60% of the food
      intake of AL rats. After 6 weeks, the effects of CR on pain behaviors and
      inflammation induced by plantar incision were examined. CR rats displayed
      significantly reduced nonevoked pain, mechanical allodynia and thermal
      hyperalgesia induced by incision, and showed decreased levels of pro-inflammatory
      cytokines in serum, peri-incisional skin tissue and ipsilateral spinal cord
      dorsal horn at 6 h and 24 h after incision. The analgesic efficiency of parecoxib
      and morphine, two agents widely used for the management of postoperative pain
      clinically, was reinforced by CR. Together, CR generates antinociceptive effects
      on postoperative incisional pain in rats, perhaps providing some improvement of
      QOL in patients with postoperative pain, and the beneficial effects may be
      attributable to the inhibition of excessive inflammation induced by surgical
      injury.

PMID- 28496117
TI  - The Guanacaste Volcanic Arc Sliver of Northwestern Costa Rica.
AB  - Recent studies have shown that the Nicoya Peninsula of northwestern Costa Rica is
      moving northwestward ~11 mm a-1 as part of a tectonic sliver. Toward the
      northwest in El Salvador the northern sliver boundary is marked by a dextral
      strike-slip fault system active since Late Pleistocene time. To the southeast
      there is no consensus on what constitutes the northern boundary of the sliver,
      although a system of active crustal faults has been described in central Costa
      Rica. Here we propose that the Haciendas-Chiripa fault system serves as the
      northeastern boundary for the sliver and that the sliver includes most of the
      Guanacaste volcanic arc, herein the Guanacaste Volcanic Arc Sliver. In this paper
      we provide constraints on the geometry and kinematics of the boundary of the
      Guanacaste Volcanic Arc Sliver that are timely and essential to any models aimed
      at resolving the driving mechanism for sliver motion. Our results are also
      critical for assessing geological hazards in northwestern Costa Rica.

PMID- 28496118
TI  - Quantum interference and heteroaromaticity of para- and meta-linked bridged
      biphenyl units in single molecular conductance measurements.
AB  - Is there a correlation between the (hetero)aromaticity of the core of a molecule
      and its conductance in a single molecular junction? To address this question,
      which is of fundamental interest in molecular electronics, oligo(arylene
      ethynylene) (OAE) molecular wires have been synthesized with core units
      comprising dibenzothiophene, carbazole, dibenzofuran and fluorene. The biphenyl
      core has been studied for comparison. Two isomeric series have been obtained with
      4-ethynylpyridine units linked to the core either at para-para positions (para
      series 1-5) or meta-meta positions (meta series 6-10). A combined experimental
      and computational study, using mechanically controlled break junction
      measurements and density functional theory calculations, demonstrates
      consistently higher conductance in the para series compared to the meta series:
      this is in agreement with increased conjugation of the pi-system in the para
      series. Within the para series conductance increases in the order of decreasing
      heteroaromaticity (dibenzothiophene < carbazole < dibenzofuran). However, the
      sequence is very different in the meta series, where dibenzothiophene ~
      dibenzofuran < carbazole. Excellent agreement between theoretical and
      experimental conductance values is obtained. Our study establishes that both
      quantum interference and heteroaromaticity in the molecular core units play
      important and inter-related roles in determining the conductance of single
      molecular junctions.

PMID- 28496119
TI  - Clinical experience with the artificial bone graft substitute Calcibon used
      following curettage of benign and low-grade malignant bone tumors.
AB  - Artificial bone graft substitutes, such as Calcibon, are becoming increasingly
      interesting as they do not cause donor site morbidity which is an advantage
      compared to autologous bone grafts. The aim of this study was to evaluate the
      efficacy and potential complications associated with the use of Calcibon. Twenty
      seven patients with benign and low-grade malignant bone tumors were treated with
      curettage and refilling of the bony cavity. Based on the radiological
      classification system of Neer, these lesions only comprised Grade I lesions,
      describing cysts that only require curettage and filling, but no additional
      treatment. At a mean follow up of six months we observed radiological
      consolidation without resorption of the bone graft substitute. These observations
      were also made at a mean follow-up of 13 and 32 months, respectively. According
      to the classification system of Goslings and Gouma we observed six surgical
      complications. Summing up, Calcibon seems to be a reliable bone graft substitute
      with low complication rates. However, delayed resorption should be expected.
      Calcibon seems to be an alternative to autologous bone grafts or allografts in
      adequate indications.

PMID- 28496120
TI  - Band Gap Engineering of Multi-Junction Solar Cells: Effects of Series Resistances
      and Solar Concentration.
AB  - Multi-junction (MJ) solar cells are one of the most promising technologies
      achieving high sunlight to electricity conversion efficiency. Resistive losses
      constitute one of the main underlying mechanisms limiting their efficiency under
      high illumination. In this paper, we study, by numerical modeling, the extent to
      which a fine-tuning of the different electronic gaps involved in MJ stacks may
      mitigate the detrimental effects of series resistance losses for concentration
      dependent and independent series resistances. Our results demonstrate that
      appropriate bandgap engineering may lead to significantly higher conversion
      efficiency at illumination levels above ~1000 suns and series resistance values
      typically exceeding 0.02 Omega cm2, due to lower operating current and, in turn,
      series resistance losses. The implications for future generations of solar cells
      aiming at an improved conversion of the solar spectrum are also addressed.

PMID- 28496121
TI  - ZnO@C (core@shell) microspheres derived from spent coffee grounds as applicable
      non-precious electrode material for DMFCs.
AB  - Although numerous reports have introduced non precious electrocatalysts for
      methanol oxidation, most of those studies did not consider the corresponding high
      onset potential which restricts utilization in real fuel cells. In this study, an
      -90 mV [vs. Ag/AgCl] onset potential non-precious electrocatalyst is introduced
      as an applicable anode material for the direct methanol fuel cells. Moreover, the
      proposed material was prepared from a cheap and abundantly existing resource; the
      spent coffee grounds. Typically, the spent coffee grounds were facilely converted
      to core@shell (ZnO@C) microspheres through a two-step approach, involving
      chemical activation and a subsequent calcination at temperature of 700  degrees
      C. Activation of the carbon derived from the spent coffee grounds was performed
      with ZnCl2 which acts as pore-forming agent as well as a precursor for the ZnO.
      The structure and morphology were characterized by (XRD), (SEM), and (TEM)
      analyses while the electrochemical characterizations was evaluated by cyclic
      voltammetry (CV) technique. Besides the comparatively very low onset potential,
      the introduced microspheres exhibited relatively high current density; 17 mA/cm2.
      Overall, based on the advantages of the green source of carbon and the good
      electrocatalytic activity, the spent coffee grounds-derived carbon can be
      considered a promise anode material for the DMFCs.

PMID- 28496124
TI  - Intelligibility of locally time-reversed speech: A multilingual comparison.
AB  - A set of experiments was performed to make a cross-language comparison of
      intelligibility of locally time-reversed speech, employing a total of 117 native
      listeners of English, German, Japanese, and Mandarin Chinese. The experiments
      enabled to examine whether the languages of three types of timing-stress-,
      syllable-, and mora-timed languages-exhibit different trends in intelligibility,
      depending on the duration of the segments that were temporally reversed. The
      results showed a strikingly similar trend across languages, especially when the
      time axis of segment duration was normalised with respect to the deviation of a
      talker's speech rate from the average in each language. This similarity is
      somewhat surprising given the systematic differences in vocalic proportions
      characterising the languages studied which had been shown in previous research
      and were largely replicated with the present speech material. These findings
      suggest that a universal temporal window shorter than 20-40 ms plays a crucial
      role in perceiving locally time-reversed speech by working as a buffer in which
      temporal reorganisation can take place with regard to lexical and semantic
      processing.

PMID- 28496122
TI  - Structural insights into a 20.8-kDa tegumental-allergen-like (TAL) protein from
      Clonorchis sinensis.
AB  - Survival of Clonorchis sinensis, a cause of human clonorchiasis, requires
      tegument proteins, which are localized to the tegumental outer surface membrane.
      These proteins play an important role in a host response and parasite survival.
      Thus, these proteins are interesting molecular targets for vaccine and drug
      development. Here, we have determined two crystal structures of the calmodulin
      like domain (amino acid [aa] positions 1-81) and dynein light chain (DLC)-like
      domain (aa 83-177) of a 20.8-kDa tegumental-allergen-like protein from Clonorchis
      sinensis (CsTAL3). The calmodulin like domain has two Ca2+-binding sites (named
      CB1 and CB2), but Ca2+ binds to only one site, CB1. The DLC-like domain has a
      dimeric conformation; the interface is formed mainly by hydrogen bonds between
      the main chain atoms. In addition, we have determined full-length structure of
      CsTAL3 in solution and showed the conformational change of CsTAL3 induced by Ca2+
      ion binding using small-angle X-ray scattering analysis and molecular dynamics
      simulations. The Ca2+-bound form has a more extended conformation than the Ca2+
      free from does. These structural and biochemical analyses will advance the
      understanding of the biology of this liver fluke and may contribute to our
      understanding of the molecular mechanism of calcium-responsive and tegumental
      allergen-like proteins.

PMID- 28496123
TI  - Systematic evaluation for effects of urine pH on calcium oxalate crystallization,
      crystal-cell adhesion and internalization into renal tubular cells.
AB  - Urine pH has been thought to be an important factor that can modulate kidney
      stone formation. Nevertheless, there was no systematic evaluation of such pH
      effect. Our present study thus addressed effects of differential urine pH (4.0
      8.0) on calcium oxalate (CaOx) crystallization, crystal-cell adhesion, crystal
      internalization into renal tubular cells, and binding of apical membrane proteins
      to the crystals. Microscopic examination revealed that CaOx monohydrate (COM),
      the pathogenic form, was crystallized with greatest size, number and total mass
      at pH 4.0 and least crystallized at pH 8.0, whereas COD was crystallized with the
      vice versa order. Fourier-transform infrared (FT-IR) spectroscopy confirmed such
      morphological study. Crystal-cell adhesion assay showed the greatest degree of
      crystal-cell adhesion at the most acidic pH and least at the most basic pH.
      Crystal internalization assay using fluorescein isothiocyanate (FITC)-labelled
      crystals and flow cytometry demonstrated that crystal internalization into renal
      tubular cells was maximal at the neutral pH (7.0). Finally, there were no
      significant differences in binding capacity of the crystals to apical membrane
      proteins at different pH. We concluded that the acidic urine pH may promote CaOx
      kidney stone formation, whereas the basic urine pH (i.e. by alkalinization) may
      help to prevent CaOx kidney stone disease.

PMID- 28496126
TI  - Fabrication-constrained nanophotonic inverse design.
AB  - A major difficulty in applying computational design methods to nanophotonic
      devices is ensuring that the resulting designs are fabricable. Here, we describe
      a general inverse design algorithm for nanophotonic devices that directly
      incorporates fabrication constraints. To demonstrate the capabilities of our
      method, we designed a spatial-mode demultiplexer, wavelength demultiplexer, and
      directional coupler. We also designed and experimentally demonstrated a compact,
      broadband 1 * 3 power splitter on a silicon photonics platform. The splitter has
      a footprint of only 3.8 * 2.5 MUm, and is well within the design rules of a
      typical silicon photonics process, with a minimum radius of curvature of 100 nm.
      Averaged over the designed wavelength range of 1400-1700 nm, our splitter has a
      measured insertion loss of 0.642 +/- 0.057 dB and power uniformity of 0.641 +/-
      0.054 dB.

PMID- 28496125
TI  - Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon
      Stapled Peptides Using Lipid Based Delivery.
AB  - Linear peptides can mimic and disrupt protein-protein interactions involved in
      critical cell signaling pathways. Such peptides however are usually protease
      sensitive and unable to engage with intracellular targets due to lack of membrane
      permeability. Peptide stapling has been proposed to circumvent these limitations
      but recent data has suggested that this method does not universally solve the
      problem of cell entry and can lead to molecules with off target cell lytic
      properties. To address these issues a library of stapled peptides was synthesized
      and screened to identify compounds that bound Mdm2 and activated cellular p53. A
      lead peptide was identified that activated intracellular p53 with negligible
      nonspecific cytotoxicity, however it still bound serum avidly and only showed a
      marginal improvement in cellular potency. These hurdles were overcome by
      successfully identifying a pyridinium-based cationic lipid formulation, which
      significantly improved the activity of the stapled peptide in a p53 reporter cell
      line, principally through increased vesicular escape. These studies underscore
      that stapled peptides, which are cell permeable and target specific, can be
      identified with rigorous experimental design and that these properties can be
      improved through use with lipid based formulations. This work should facilitate
      the clinical translation of stapled peptides.

PMID- 28496127
TI  - Controlling magnetic transition of monovacancy graphene by shear distortion.
AB  - The effect of shear distortion on the vacancy induced magnetism in graphene is
      investigated using extensive first-principles calculations. It is found that
      shear distortion can lead to magnetic transition between two states with high and
      low magnetic moments. Such a transition is reversible and results from the
      breaking of the in-plane symmetry of the local atoms, which reverses spin
      polarization of the pi bands of the vacancy states near the Fermi level and leads
      to the change of magnetic transition by 1 uB. This finding opens the possibility
      for nanomechanical control of graphene magnetism and has potential applications
      in spintronics and magnetic sensing.

PMID- 28496129
TI  - Acoustoelectric Current in Graphene Nanoribbons.
AB  - Surface acoustic waves (SAWs) propagating on piezoelectric substrates offer a
      convenient, contactless approach to probing the electronic properties of low
      dimensional charge carrier systems such as graphene nanoribbons (GNRs). SAWs can
      also be used to transport and manipulate charge for applications such as
      metrology and quantum information. In this work, we investigate the
      acoustoelectric effect in GNRs, and show that an acoustoelectric current can be
      generated in GNRs with physical widths as small as 200 nm at room temperature.
      The positive current in the direction of the SAWs, which corresponds to the
      transportation of holes, exhibits a linear dependence on SAW intensity and
      frequency. This is consistent with the description of the interaction between the
      charge carriers in the GNRs and the piezoelectric fields associated with the SAWs
      being described by a relatively simple classical relaxation model. Somewhat
      counter-intuitively, as the GNR width is decreased, the measured acoustoelectric
      current increases. This is thought to be caused by an increase of the carrier
      mobility due to increased doping arising from damage to the GNR edges.

PMID- 28496128
TI  - A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for
      Obesity in Human Adipose Tissue.
AB  - To explore novel molecular mechanisms underlying obesity, we applied a systems
      genetics framework to integrate risk genetic loci from the largest body mass
      index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and
      microRNA profiling in adipose tissue from 200 subjects. One module was identified
      to be most significantly associated with obesity and other metabolic traits. We
      identified eight hub genes which likely play important roles in obesity
      metabolism and identified microRNAs that significantly negatively correlated with
      hub genes. This module was preserved in other three test gene expression
      datasets, and all hub genes were consistently downregulated in obese subjects
      through the meta-analysis. Gene GPD1L had the highest connectivity and was
      identified a key causal regulator in the module. Gene GPD1L was significantly
      negatively correlated with the expression of miR-210, which was experimentally
      validated that miR-210 regulated GPD1L protein level through direct interaction
      with its mRNA three prime untranslated region (3'-UTR). GPD1L was found to be
      upregulated during weight loss and weight maintenance induced by low calorie diet
      (LCD), while downregulated during weight gain induced by high-fat diet (HFD). The
      results indicated that increased GPD1L in adipose tissue may have a significant
      therapeutic potential in reducing obesity and insulin resistance.

PMID- 28496130
TI  - An Aqueous-Based Approach for Fabrication of PVDF/MWCNT Porous Composites.
AB  - In this paper, we demonstrate the fabrication of conductive porous polymers based
      on foaming of an aqueous dispersion of polymeric particles and multi-walled
      carbon nanotubes (CNT). By tuning the surface energy of the constituents, we
      direct their preferential adsorption at the air-liquid (bubble) interface or
      within the liquid film between the bubbles. Sintering this bi-constituent foam
      yields solid closed-cell porous structure which can be electrically conductive if
      CNT are able to form a conductive path. We measure transport (electrical and
      thermal), mechanical, and morphological properties of such porous structures as a
      function of CNT loading and the method used for their surface functionalization.
      For a fixed polymer volume fraction, we demonstrate the limit in which increasing
      CNT results in decreasing the mechanical strength of the sample due to lack of
      adequate polymer-CNT bond. Such lightweight conductive porous composites are
      considered in applications including EMI shielding, electrostatic discharge
      protection, and electrets.

PMID- 28496131
TI  - Leveraging multiple genomic data to prioritize disease-causing indels from exome
      sequencing data.
AB  - The emergence of exome sequencing in recent years has enabled rapid and cost
      effective detection of genetic variants in coding regions and offers a great
      opportunity to combine sequencing experiments with subsequent computational
      analysis for dissecting genetic basis of human inherited diseases. However, this
      strategy, though successful in practice, still faces such challenges as limited
      sample size and substantial number or diversity of candidate variants. To
      overcome these obstacles, researchers have been concentrated in the development
      of advanced computational methods and have recently achieved great progress for
      analysing single nucleotide variant. Nevertheless, it still remains unclear on
      how to analyse indels, another type of genetic variant that accounts for
      substantial proportion of known disease-causing variants. In this paper, we
      proposed an integrative method to effectively identify disease-causing indels
      from exome sequencing data. Specifically, we put forward a statistical method to
      combine five functional prediction scores, four genic association scores and a
      genic intolerance score to produce an integrated p-value, which could then be
      used for prioritizing candidate indels. We performed extensive simulation studies
      and demonstrated that our method achieved high accuracy in uncovering disease
      causing indels. Our software is available at
      http://bioinfo.au.tsinghua.edu.cn/jianglab/IndelPrioritizer/.

PMID- 28496132
TI  - Serum sonic hedgehog (SHH) and interleukin-(IL-6) as dual prognostic biomarkers
      in progressive metastatic breast cancer.
AB  - Serum from one hundred and ten breast cancer patients and thirty healthy female
      volunteers, were prospectively collected and evaluated for serum levels of Shh
      and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All
      patients were regularly monitored for event free survival (EFS) and overall
      survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels.
      In patients with progressive metastatic BC, both serum Shh and IL-6
      concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients,
      respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p
      = 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended
      to increase with metastatic progression and lymph node positivity. High serum Shh
      and IL-6 levels were associated with poor EFS and OS opposite to the negative or
      lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL
      6 were mainly observed in BC patients who had a significantly higher risk of
      early recurrence and bone metastasis, and associated with a worse survival for
      patients with progressive metastatic BC. Further studies are warranted for
      validating these biomarkers as prognostic tools in a larger patient cohort and in
      a longer follow-up study.

PMID- 28496133
TI  - Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by
      Modulating AMPKalpha Activity.
AB  - Folate, an essential micronutrient, is a critical cofactor in one-carbon
      metabolism for many cellular pathways including DNA synthesis, metabolism and
      maintenance. Folate deficiency has been associated with an increased risk of
      neurological disease, cancer and cognitive dysfunction. Dihydrofolate reductase
      (DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR
      activity in oligodendrocyte development has not been fully understood. Here we
      show that folate enhances oligodendrocyte maturation both in vitro and in vivo,
      which is accompanied with upregulation of oligodendrocyte-specific DHFR
      expression. On the other hand, pharmacological inhibition of DHFR by methotrexate
      (MTX) causes severe defects in oligodendrocyte survival and differentiation,
      which could be reversed by folate intake. We further demonstrate that folate
      activates a metabolic regulator AMPKalpha to promote oligodendrocyte survival and
      differentiation. Moreover, activation of AMPKalpha partially rescues
      oligodendrocyte defects caused by DHFR-inhibition both in vitro and in vivo.
      Taken together, these findings identify a previously uncharacterized role of
      folate/DHFR/AMPKalpha axis in regulating oligodendrocyte survival and myelination
      during CNS development.

PMID- 28496134
TI  - Inkjet printing of NiO films and integration as hole transporting layers in
      polymer solar cells.
AB  - Stability concerns of organic solar cell devices have led to the development of
      alternative hole transporting layers such as NiO which lead to superior device
      life times over conventional Poly(3,4-ethylenedioxythiophene) Polystyrene
      sulfonate (PEDOT:PSS) buffered solar cells. From the printability of such
      devices, it is imperative to be able to print NiO layers in the organic solar
      cell devices with normal architecture which has so far remained unreported. In
      this manuscript, we report on the successful ink-jet printing of very thin NiO
      thin films with controlled thickness and morphology and their integration in
      organic solar cell devices. The parameters that were found to strongly affect the
      formation of a thin yet continuous NiO film were substrate surface treatment,
      drop spacing, and substrate temperature during printing. The effect of these
      parameters was investigated through detailed morphological characterization using
      optical and atomic force microscopy and the results suggested that one can
      achieve a transmittance of ~89% for a ~18 nm thin NiO film with uniform structure
      and morphology, fabricated using a drop spacing of 50 MUm and a heat treatment
      temperature of 400  degrees C. The devices fabricated with printed NiO hole
      transporting layers exhibit power conversion efficiencies comparable to the
      devices with spin coated NiO films.

PMID- 28496135
TI  - Isolated Bacillus subtilis strain 330-2 and its antagonistic genes identified by
      the removing PCR.
AB  - Plant growth-promoting bacteria (PGPB) may trigger tolerance against
      biotic/abiotic stresses and growth enhancement in plants. In this study, an
      endophytic bacterial strain from rapeseed was isolated to assess its role in
      enhancing plant growth and tolerance to abiotic stresses, as well as banded leaf
      and sheath blight disease in maize. Based on 16S rDNA and BIOLOG test analysis,
      the 330-2 strain was identified as Bacillus subtilis. The strain produced indole
      3-acetic acid, siderophores, lytic enzymes and solubilized different sources of
      organic/inorganic phosphates and zinc. Furthermore, the strain strongly
      suppressed the in vitro growth of Rhizoctonia solani AG1-IA, Botrytis cinerea,
      Fusarium oxysporum, Alternaria alternata, Cochliobolus heterostrophus, and
      Nigrospora oryzae. The strain also significantly increased the seedling growth
      (ranging 14-37%) of rice and maize. Removing PCR analysis indicated that 114
      genes were differentially expressed, among which 10%, 32% and 10% were involved
      in antibiotic production (e.g., srfAA, bae, fen, mln, and dfnI), metabolism
      (e.g., gltA, pabA, and ggt) and transportation of nutrients (e.g., fhu, glpT, and
      gltT), respectively. In summary, these results clearly indicate the effectiveness
      and mechanisms of B. subtilis strain 330-2 in enhancing plant growth, as well as
      tolerance to biotic/abiotic stresses, which suggests that the strain has great
      potential for commercialization as a vital biological control agent.

PMID- 28496136
TI  - The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when
      fused to several antigens.
AB  - A persistent goal of vaccine development is the enhancement of the immunogenicity
      of antigens while maintaining safety. One strategy involves alteration of the
      presentation of the antigen by combining antigens with a multimeric scaffold.
      Multi-antigen vaccines are under development, and there are presently far more
      candidate antigens than antigen scaffolding strategies. This is potentially
      problematic, since prior immunity to a scaffold may inhibit immune responses to
      the antigen-scaffold combination. In this study, a series of domains from S.
      aureus which have been shown to crystallise into multimeric structures have been
      examined for their scaffolding potential. Of these domains, SAR1376, a 62 amino
      acid member of the 4-oxalocrotonate tautomerase (4-OT) family, was pro
      immunogenic in mice when fused to a range of pathogen antigens from both S.
      aureus and P. falciparum, and delivered by either DNA vaccination, viral vector
      vaccines or as protein-in-adjuvant formulations. The adjuvant effect did not
      depend on enzymatic activity, but was abrogated by mutations disrupting the
      hexameric structure of the protein. We therefore propose that SAR1376, and
      perhaps other members of the 4-OT protein family, represent very small domains
      which can be fused to a wide range of antigens, enhancing immune responses
      against them.

PMID- 28496137
TI  - Tumor suppressor menin is required for subunit-specific nAChR alpha5
      transcription and nAChR-dependent presynaptic facilitation in cultured mouse
      hippocampal neurons.
AB  - In the central nervous system (CNS), cholinergic transmission induces synaptic
      plasticity that is required for learning and memory. However, our understanding
      of the development and maintenance of cholinergic circuits is limited, as the
      factors regulating the expression and clustering of neuronal nicotinic
      acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our
      group have implicated calpain-dependent proteolytic fragments of menin, the
      product of the MEN1 tumor suppressor gene, in coordinating the transcription and
      synaptic clustering of nAChRs in invertebrate central neurons. Here, we sought to
      determine whether an analogous cholinergic mechanism underlies menin's
      synaptogenic function in the vertebrate CNS. Our data from mouse primary
      hippocampal cultures demonstrate that menin and its calpain-dependent C-terminal
      fragment (C-menin) regulate the subunit-specific transcription and synaptic
      clustering of neuronal nAChRs, respectively. MEN1 knockdown decreased nAChR
      alpha5 subunit expression, the clustering of alpha7 subunit-containing nAChRs at
      glutamatergic presynaptic terminals, and nicotine-induced presynaptic
      facilitation. Moreover, the number and function of glutamatergic synapses was
      unaffected by MEN1 knockdown, indicating that the synaptogenic actions of menin
      are specific to cholinergic regulation. Taken together, our results suggest that
      the influence of menin on synapse formation and synaptic plasticity occur via
      modulation of nAChR channel subunit composition and functional clustering.

PMID- 28496138
TI  - Severe bilateral ischemic-reperfusion renal injury: hyperacute and acute changes
      in apparent diffusion coefficient, T1, and T2 mapping with immunohistochemical
      correlations.
AB  - The aim of this study was to investigate the hyperacute and acute changes in
      apparent diffusion coefficient (ADC), T1, and T2 mapping in rat kidneys after
      severe bilateral renal ischemic-reperfusion injury (IRI). After baseline MRI, 24
      Spraque-Dawley rats with renal IRI were divided equally as group 1 (post-IRI MRI
      at 6 hours, days 1, 3, and 7) and groups 2, 3, and 4 (post-IRI MRI at 6 hours; 6
      hours and day 1; 6 hours, days 1 and 3, respectively), while six other rats
      without IRI (group 5) were used as sham control. ADC, T1, and T2 values of the
      cortex and outer and inner stripes of outer medulla (OSOM and ISOM), and
      immunohistochemical studies assessing monocyte chemoattractant protein-1 (MCP-1),
      CD68+ cells, tubular cast formation, and collagen deposition in three zones at
      different time points were evaluated. Significantly reduced ADCs in OSOM and ISOM
      are noninvasive biomarkers denoting hyperacute damages after IRI. Linear
      regression analysis revealed a significant inverse correlation between 6
      hour/baseline ADC ratios and MCP-1 staining (P < 0.001, r2 = 0.738). ADC, T1, and
      T2 values are useful for assessing variable IRI changes in different layers
      depending on underlying microstructural and histopathological changes at
      different time points.

PMID- 28496139
TI  - Operational lifetimes of organic light-emitting diodes dominated by Forster
      resonance energy transfer.
AB  - Organic light-emitting diodes are a key technology for next-generation
      information displays because of their low power consumption and potentially long
      operational lifetimes. Although devices with internal quantum efficiencies of
      approximately 100% have been achieved using phosphorescent or thermally activated
      delayed fluorescent emitters, a systematic understanding of materials suitable
      for operationally stable devices is lacking. Here we demonstrate that the
      operational stability of phosphorescent devices is nearly proportional to the
      Forster resonance energy transfer rate from the host to the emitter when
      thermally activated delayed fluorescence molecules are used as the hosts. We find
      that a small molecular size is a requirement for thermally activated delayed
      fluorescence molecules employed as phosphorescent hosts; in contrast, an
      extremely small energy gap between the singlet and triplet excited states, which
      is essential for an efficient thermally activated delayed fluorescent emitter, is
      unnecessary in the phosphorescent host.

PMID- 28496140
TI  - The Impact of a Severe Drought on Dust Lifting in California's Owens Lake Area.
AB  - Mineral dust aerosols are responsible for some of the largest sources of
      uncertainties in our current understanding of climate change. Here we show that a
      severe drought is having a significant impact in one of largest sources of
      mineral dust aerosols of the U.S., the Owens Lake area in California's southwest.
      Measurements of aerosol concentration (PM2.5 particle matter) in the Owens Lake
      salty playa show that the annual mean concentration of PM2.5 aerosol has been
      increasing steadily since the beginning of the current drought, with periods of
      high aerosol concentration increasing from 4 months in 2013 to 9 months in 2015.
      Interestingly, the PM2.5 aerosol concentration usually increases abruptly from
      less than ~0.05 mg/m3 to ~0.25 mg/m3. This occurs when saltation events break
      salt crusts produced by the efflorescence of brine in the salty playa. The brine
      is produced by either rainfall or runoff water. Based on this observation, we
      hypothesize that there is an upper limit of ~0.25 mg/m3 in the annual mean PM2.5
      aerosols concentration in the Owens Lake basin that might limit the impact of
      mineral dust aerosols on climate. Indeed, the upper annual limit of ~0.25 mg/m3
      has been nearly reached during the current drought.

PMID- 28496141
TI  - A randomized comparison of the prone ventilation endotracheal tube versus the
      traditional endotracheal tube in adult patients undergoing prone position
      surgery.
AB  - Endotracheal tube displacement or dislocation is a severe complication that can
      occur in patients who require prone position ventilation. We hypothesized the
      prone position tube (PPT) would reduce the incidence of displacement of an
      endotracheal tube in an adult prone operation compared to a traditional tube
      (TT). A total of 80 adult patients undergoing neurosurgery or spine surgery were
      recruited. Sixty patients with prone position ventilation were randomly divided
      into the traditional routine endotracheal tube group (Group TT, n = 30) and the
      prone position ventilation endotracheal tube group (Group PPT, n = 30). The
      primary outcome measures were the incidence of the endotracheal tube displacement
      during surgery, and the secondary outcomes were symptoms of sore throat,
      dysphagia and dysphonia during follow-up in the post-anesthesia care unit (PACU).
      The incidence of tube displacement was significantly lower in the PPT group (0
      [0%] of 30 patients) compared to the TT group (22 [73.3%] of 30 patients; odds
      ratio [OR] 0.73, 95% CI 0.591-0.910; P = 0.005). There was no statistical
      difference in sore throat, dysphagia and vocal function between the two groups (P
      > 0.05) during follow-up. Compared to the traditional tube, the improved prone
      positon tube reduced the incidence of displacement of the endotracheal tube. This
      study was registered with ClinicalTrials.gov on April 29, 2015 (No. NCT02449356).

PMID- 28496142
TI  - Src-homology protein tyrosine phosphatase-1 agonist, SC-43, reduces liver
      fibrosis.
AB  - This study aimed to investigate the role of src-homology protein tyrosine
      phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3)
      pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The
      antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1
      activity, was evaluated in two fibrosis mouse models by carbon tetrachloride
      induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate
      cells (HSCs) were used for mechanistic investigations. The results showed that
      SHP-1 protein primarily localized in fibrotic areas of human and mouse livers. SC
      43 treatment reduced the activated HSCs and thus effectively prevented and
      regressed liver fibrosis in both fibrosis mouse models and improved mouse
      survival. In vitro studies revealed that SC-43 promoted HSC apoptosis, increased
      the SHP-1 activity and inhibited phospho-STAT3. The enhanced SHP-1 activity in
      HSCs significantly inhibited HSC proliferation, whereas SHP-1 inhibition rescued
      SC-43-induced HSC apoptosis. Furthermore, SC-43 interacted with the N-SH2 domain
      of SHP-1 to enhance the activity of SHP-1 as its antifibrotic mechanism. In
      conclusion, the SHP-1-STAT3 pathway is crucial in fibrogenesis. SC-43
      significantly ameliorates liver fibrosis through SHP-1 upregulation. A SHP-1
      targeted antifibrotic therapy may represent a druggable strategy for antifibrotic
      drug discovery.

PMID- 28496143
TI  - Serum Metabolomic Profiles for Breast Cancer Diagnosis, Grading and Staging by
      Gas Chromatography-Mass Spectrometry.
AB  - Detection of metabolic signature for breast cancer (BC) has the potential to
      improve patient prognosis. This study identified potentially significant
      metabolites differentiating between breast cancer patients and healthy controls
      to help in diagnosis, grading, staging and determination of neoadjuvant status.
      Serum was collected from 152 pre-operative breast cancer (BC) patients and 155
      healthy controls in this case-controlled study. Gas chromatography-mass
      spectrometry (GC-MS) was used to obtain metabolic profiles followed by
      chemometric analysis with the identification of significantly differentiated
      metabolites including 7 for diagnosis, 18 for grading, 23 for staging, 15 for
      stage III subcategory and 10 for neoadjuvant status (p-value < 0.05). Partial
      Least Square Discriminant Analysis (PLS-DA) model revealed a distinct separation
      between healthy controls and BC patients with a sensitivity of 96% and
      specificity of 100% on external validation. Models for grading, staging and
      neoadjuvant status were built with Decision Tree Algorithm with predictive
      accuracy of 71.5%, 71.3% and 79.8% respectively. Pathway analysis revealed
      increased glycolysis, lipogenesis, and production of volatile organic metabolites
      indicating the metabolic alterations in breast cancer.

PMID- 28496144
TI  - Alkali-created rich properties in grapheme nanoribbons: Chemical bondings.
AB  - The alkali-adsorbed graphene nanoribbons exhibit the feature-rich electronic and
      magnetic properties. From the first-principles calculations, there are only few
      adatom-dominated conduction bands, and the other conduction and valence bands are
      caused by carbon atoms. A lot of free electrons are revealed in the occupied
      alkali- and carbon-dependent conduction bands. Energy bands are sensitive to the
      concentration, distribution and kind of adatom and the edge structure, while the
      total linear free carrier density only relies on the first one. These mainly
      arise from a single s - 2p z orbital hybridization in the adatom-carbon bond.
      Specifically, zigzag systems can present the anti-ferromagnetic ordering across
      two edges, ferromagnetic ordering along one edge and non-magnetism, being
      reflected in the edge-localized energy bands with or without spin splitting. The
      diverse energy dispersions contribute many special peaks in density of states.
      The critical chemical bonding and the distinct spin configuration could be
      verified from the experimental measurements.

PMID- 28496145
TI  - Market watch: Trends in pharmaceutical company R&D spending: 2005-2015.

PMID- 28496147
TI  - Combination products: modernizing the regulatory paradigm.
AB  - New opportunities to develop innovative - and often complex - products that
      combine drugs, devices and/or biological components are rapidly emerging, raising
      questions about how such products should be regulated. Here, we discuss the
      ongoing efforts of the FDA to develop a modern, transparent, flexible and
      consistent science-based regulatory approach for combination products.

PMID- 28496148
TI  - Genetic structure of Cercospora beticola populations on Beta vulgaris in New York
      and Hawaii.
AB  - Cercospora leaf spot (CLS), caused by Cercospora beticola, is a major disease of
      Beta vulgaris worldwide. No sexual stage is known for C. beticola but in its
      asexual form it overwinters on infected plant debris as pseudostromata, and
      travels short distances by rain splash-dispersed conidiospores. Cercospora
      beticola infects a broad range of host species and may be seedborne. The relative
      contribution of these inoculum sources to CLS epidemics on table beet is not well
      understood. Pathogen isolates collected from table beet, Swiss chard and common
      lambsquarters in mixed-cropping farms and monoculture fields in New York and
      Hawaii, USA, were genotyped (n = 600) using 12 microsatellite markers. All
      isolates from CLS symptoms on lambsquarters were identified as C. chenopodii.
      Sympatric populations of C. beticola derived from Swiss chard and table beet were
      not genetically differentiated. Results suggested that local (within field)
      inoculum sources may be responsible for the initiation of CLS epidemics in mixed
      cropping farms, whereas external sources of inoculum may be contributing to CLS
      epidemics in the monoculture fields in New York. New multiplex PCR assays were
      developed for mating-type determination for C. beticola. Implications of these
      findings for disease management are discussed.

PMID- 28496146
TI  - The antifungal pipeline: a reality check.
AB  - Invasive fungal infections continue to appear in record numbers as the
      immunocompromised population of the world increases, owing partially to the
      increased number of individuals who are infected with HIV and partially to the
      successful treatment of serious underlying diseases. The effectiveness of current
      antifungal therapies - polyenes, flucytosine, azoles and echinocandins (as
      monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or
      specific therapies) - in the management of these infections has plateaued.
      Although these drugs are clinically useful, they have several limitations, such
      as off-target toxicity, and drug-resistant fungi are now emerging. New
      antifungals are therefore needed. In this Review, I discuss the robust and
      dynamic antifungal pipeline, including results from preclinical academic efforts
      through to pharmaceutical industry products, and describe the targets,
      strategies, compounds and potential outcomes.

PMID- 28496149
TI  - The active site structure and catalytic mechanism of arsenite oxidase.
AB  - Arsenite oxidase is thought to be an ancient enzyme, originating before the
      divergence of the Archaea and the Bacteria. We have investigated the nature of
      the molybdenum active site of the arsenite oxidase from the Alphaproteobacterium
      Rhizobium sp. str. NT-26 using a combination of X-ray absorption spectroscopy and
      computational chemistry. Our analysis indicates an oxidized Mo(VI) active site
      with a structure that is far from equilibrium. We propose that this is an entatic
      state imposed by the protein on the active site through relative orientation of
      the two molybdopterin cofactors, in a variant of the Ray-Dutt twist of classical
      coordination chemistry, which we call the pterin twist hypothesis. We discuss the
      implications of this hypothesis for other putatively ancient molybdopterin-based
      enzymes.

PMID- 28496150
TI  - Long non-coding RNA PARTICLE bridges histone and DNA methylation.
AB  - PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced
      Circulating LncRNA) expression is transiently elevated following low dose
      irradiation typically encountered in the workplace and from natural sources. This
      long non-coding RNA recruits epigenetic silencers for cis-acting repression of
      its neighbouring Methionine adenosyltransferase 2A gene. It now emerges that
      PARTICLE operates as a trans-acting mediator of DNA and histone lysine
      methylation. Chromatin immunoprecipitation sequencing (ChIP-seq) and
      immunological evidence established elevated PARTICLE expression linked to
      increased histone 3 lysine 27 trimethylation. Live-imaging of dbroccoli-PARTICLE
      revealing its dynamic association with DNA methyltransferase 1 was confirmed by
      flow cytometry, immunoprecipitation and direct competitive binding interaction
      through electrophoretic mobility shift assay. Acting as a regulatory docking
      platform, the long non-coding RNA PARTICLE serves to interlink epigenetic
      modification machineries and represents a compelling innovative component
      necessary for gene silencing on a global scale.

PMID- 28496151
TI  - Exploring nonlinear topological states of matter with exciton-polaritons: Edge
      solitons in kagome lattice.
AB  - Matter in nontrivial topological phase possesses unique properties, such as
      support of unidirectional edge modes on its interface. It is the existence of
      such modes which is responsible for the wonderful properties of a topological
      insulator - material which is insulating in the bulk but conducting on its
      surface, along with many of its recently proposed photonic and polaritonic
      analogues. We show that exciton-polariton fluid in a nontrivial topological phase
      in kagome lattice, supports nonlinear excitations in the form of solitons built
      up from wavepackets of topological edge modes - topological edge solitons. Our
      theoretical and numerical results indicate the appearance of bright, dark and
      grey solitons dwelling in the vicinity of the boundary of a lattice strip. In a
      parabolic region of the dispersion the solitons can be described by envelope
      functions satisfying the nonlinear Schrodinger equation. Upon collision, multiple
      topological edge solitons emerge undistorted, which proves them to be true
      solitons as opposed to solitary waves for which such requirement is waived.
      Importantly, kagome lattice supports topological edge mode with zero group
      velocity unlike other types of truncated lattices. This gives a finer control
      over soliton velocity which can take both positive and negative values depending
      on the choice of forming it topological edge modes.

PMID- 28496152
TI  - Rapid, Self-driven Liquid Mixing on Open-Surface Microfluidic Platforms.
AB  - Self-driven surface micromixers (SDSM) relying on patterned-wettability
      technology provide an elegant solution for low-cost, point-of-care (POC) devices
      and lab-on-a-chip (LOC) applications. We present a SDSM fabricated by
      strategically patterning three wettable wedge-shaped tracks onto a non-wettable,
      flat surface. This SDSM operates by harnessing the wettability contrast and the
      geometry of the patterns to promote mixing of small liquid volumes (uL droplets)
      through a combination of coalescence and Laplace pressure-driven flow. Liquid
      droplets dispensed on two juxtaposed branches are transported to a coalescence
      station, where they merge after the accumulated volumes exceed a threshold.
      Further mixing occurs during capillary-driven, advective transport of the
      combined liquid over the third wettable track. Planar, non-wettable "islands" of
      different shapes are also laid on this third track to alter the flow in such a
      way that mixing is augmented. Several SDSM designs, each with a unique
      combination of island shapes and positions, are tested, providing a greater
      understanding of the different mixing regimes on these surfaces. The study offers
      design insights for developing low-cost surface microfluidic mixing devices on
      open substrates.

PMID- 28496153
TI  - Michaelis-Menten kinetics of soil respiration feedbacks to nitrogen deposition
      and climate change in subtropical forests.
AB  - China experiences some of the highest rates of anthropogenic nitrogen deposition
      globally, with further increases projected. Understanding of soil feedbacks to
      the combined anthropogenic influences of climate change and nitrogen deposition
      in these systems is critical to improve predictive abilities for future climate
      scenarios. Here we used a Michaelis-Menten substrate-based kinetics framework to
      explore how soil CO2 production (Rsoil) responds to changes in temperature and
      available soil nitrogen (N) by combining field experiments with laboratory
      manipulations from sites experiencing elevated rates of anthropogenic N
      deposition but varying in soil N availabiltiy. The temperature sensitivity of
      Rsoil was strongly influenced by labile C additions. Furthermore, estimation of
      the temperature response of the Michaelis-Menten parameters supports the use of
      substrate-based kinetics in modeling efforts. Results from both field and
      laboratory experiments demonstrated a general decrease in Rsoil with increasing
      soil available N that was variably dependent on carbon (C) availability. Both the
      field and the laboratory measurements demonstrated a consistent decrease in the
      Michaelis-Menten parameter kM with increasing soil available N, indicating an
      increase in the efficiency of soil C decomposition with increasing N.
      Furthermore, these results provide evidence of interactions between N deposition
      and temperature sensitivity, which could influence C storage under combined
      anthropogenic global change drivers.

PMID- 28496154
TI  - Young children copy cumulative technological design in the absence of action
      information.
AB  - The ratchet effect - the accumulation of beneficial changes in cultural products
      beyond a level that individuals could reach on their own - is a topic of
      increasing interest. It is currently debated which social learning mechanisms
      allow for the generation and transmission of cumulative culture. This study
      focused on transmission, investigating whether 4- to 6-year-old children were
      able to copy cumulative technological design and whether they could do so without
      action information (emulation). We adapted the spaghetti tower task, previously
      used to test for accumulation of culture in human adults. A baseline condition
      established that the demonstrated tower design was beyond the innovation skills
      of individual children this age and so represented a culture-dependent product
      for them. There were 2 demonstration conditions: a full demonstration (actions
      plus (end-)results) and an endstate- demonstration (end-results only). Children
      in both demonstration conditions built taller towers than those in the baseline.
      Crucially, in both demonstration conditions some children also copied the
      demonstrated tower. We provide the first evidence that young children learn from,
      and that some of them even copy, cumulative technological design, and that - in
      line with some adult studies - action information is not always necessary to
      transmit culture-dependent traits.

PMID- 28496155
TI  - Selection of reference genes for microRNA analysis associated to early stress
      response to handling and confinement in Salmo salar.
AB  - MicroRNAs are key non-coding RNA molecules that play a relevant role in the
      regulation of gene expression through translational repression and/or transcript
      cleavage during normal development and physiological adaptation processes like
      stress. Quantitative reverse transcription polymerase chain reaction (RT-qPCR)
      has become the approach normally used to determine the levels of microRNAs.
      However, this approach needs the use of endogenous reference. An improper
      selection of endogenous references can result in confusing interpretation of
      data. The aim of this study was to identify and validate appropriate endogenous
      reference miRNA genes for normalizing RT-qPCR survey of miRNAs expression in four
      different tissues of Atlantic salmon, under handling and confinement stress
      conditions associated to early or primary stress response. Nine candidate
      reference normalizers, including microRNAs and nuclear genes, normally used in
      vertebrate microRNA expression studies were selected from literature, validated
      by RT-qPCR and analyzed by the algorithms geNorm and NormFinder. The results
      revealed that the ssa-miR-99-5p gene was the most stable overall and that ssa-miR
      99-5p and ssa-miR-23a-5p genes were the best combination. Moreover, the
      suitability of ssa-miR-99-5p and ssa-miR-23a-5p as endogeneuos reference genes
      was demostrated by the expression analysis of ssa-miR-193-5p gene.

PMID- 28496156
TI  - Hybrid Three-Mode Correlation and Squeezing in a Pr3+:YSO Crystal.
AB  - We report the generation of three-mode hybrid intensity-noise correlation and
      intensity-difference squeezing of spontaneous parametric four-wave mixing (SP
      FWM) and fourth-order fluorescence (FL) signals in the heteronuclear-like (three
      level Lambda-type) molecular structure of a Pr3+:Y2SiO5 (Pr3+:YSO) crystal using
      the nonlinear cross-Kerr effect under a polarized dressing effect. In the semi
      classical view of a Kerr nonlinear medium, the amplitude of two-mode hybrid
      correlations of this kind is subject to a limit determined by the hybrid
      maximally entangled state. Whereas the degree of correlation and squeezing is
      determined by the dressing effects of the input laser fields participating in the
      SP-FWM process. We also find that the variations in magnitude of three-mode
      hybrid intensity-noise correlation and intensity-difference squeezing are
      consistent with nonlinear cross-Kerr processes. Such a three-mode hybrid signal
      may have potential applications in long-distance communication, dense coding, all
      optical communication and quantum storage on photonic chips.

PMID- 28496157
TI  - RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation
      in breast cancer.
AB  - Breast cancer is a complex heterogeneous disease. Common hallmark features of
      cancer can be found. Their origin may be traced back to their intricate
      relationships governing regulatory programs during the development of this
      disease. To unveil distinctive features of the transcriptional regulation program
      in breast cancer, a pipeline for RNA-seq analysis in 780 breast cancer and 101
      healthy breast samples, at gene expression and network level, was implemented.
      Inter-chromosomal relationships between genes resulted strikingly scarce in a
      cancer network, in comparison to its healthy counterpart. We suggest that inter
      chromosomal regulation loss may be a novel feature in breast cancer. Additional
      evidence was obtained by independent validation in microarray and Hi-C data as
      well as supplementary computational analyses. Functional analysis showed
      upregulation in processes related to cell cycle and division; while migration,
      adhesion and cell-to-cell communication, were downregulated. Both the BRCA1 DNA
      repairing signalling and the Estrogen-mediated G1/S phase entry pathways were
      found upregulated. In addition, a synergistic underexpression of the gamma
      protocadherin complex, located at Chr5q31 is also shown. This region has
      previously been reported to be hypermethylated in breast cancer. These findings
      altogether provide further evidence for the central role of transcriptional
      regulatory programs in shaping malignant phenotypes.

PMID- 28496158
TI  - Microbiota: Clostridia protect from gut infections in early life.

PMID- 28496160
TI  - Corrigendum: Metal homeostasis and resistance in bacteria.

PMID- 28496161
TI  - Bacterial physiology: Hsp90 is the hot guy for Shewanella oneidensis.

PMID- 28496159
TI  - A comprehensive guide to pilus biogenesis in Gram-negative bacteria.
AB  - Pili are crucial virulence factors for many Gram-negative pathogens. These
      surface structures provide bacteria with a link to their external environments by
      enabling them to interact with, and attach to, host cells, other surfaces or each
      other, or by providing a conduit for secretion. Recent high-resolution structures
      of pilus filaments and the machineries that produce them, namely chaperone-usher
      pili, type IV pili, conjugative type IV secretion pili and type V pili, are
      beginning to explain some of the intriguing biological properties that pili
      exhibit, such as the ability of chaperone-usher pili and type IV pili to stretch
      in response to external forces. By contrast, conjugative pili provide a conduit
      for the exchange of genetic information, and recent high-resolution structures
      have revealed an integral association between the pilin subunit and a
      phospholipid molecule, which may facilitate DNA transport. In addition, progress
      in the area of cryo-electron tomography has provided a glimpse of the overall
      architecture of the type IV pilus machinery. In this Review, we examine recent
      advances in our structural understanding of various Gram-negative pilus systems
      and discuss their functional implications.

PMID- 28496162
TI  - Viral pathogenesis: Masked by macrophages.

PMID- 28496163
TI  - Reshaping the tree of life.
AB  - This month's Genome Watch highlights how metagenomics is continuing to reveal the
      diversity of microorganisms in the environment and how it is challenging and
      expanding our understanding of how life evolved on Earth.

PMID- 28496164
TI  - Biofilms: New ways for streptococci to settle down.

PMID- 28496165
TI  - Corrigendum: Assembly, structure, function and regulation of type III secretion
      systems.

PMID- 28496166
TI  - Measurement of local temperature increments induced by cultured HepG2 cells with
      micro-thermocouples in a thermally stabilized system.
AB  - To monitor the temperature distribution of a cell and its changes under varied
      conditions is currently a technical challenge. A variety of non-contact methods
      used for measuring cellular temperature have been developed, where changes of
      local temperature at cell-level and sub-cell-level are indirectly calculated
      through the changes in intensity, band-shape, bandwidth, lifetime or polarization
      anisotropy of the fluorescence spectra recorded from the nano-sized fluorescent
      materials pre-injected into the target cell. Unfortunately, the optical
      properties of the fluorescent nano-materials may be affected by complicated
      intracellular environment, leading to unexpected measurement errors and
      controversial arguments. Here, we attempted to offer an alternative approach for
      measuring the absolute increments of local temperature in micro-Testing Zones
      induced by live cells. In this method, built-in high-performance micro
      thermocouple arrays and double-stabilized system with a stability of 10 mK were
      applied. Increments of local temperature close to adherent human hepatoblastoma
      (HepG2) cells were continuously recorded for days without stimulus, showing
      frequent fluctuations within 60 mK and a maximum increment by 285 mK. This method
      may open a door for real-time recording of the absolute local temperature
      increments of individual cells, therefore offering valuable information for cell
      biology and clinical therapy in the field of cancer research.

PMID- 28496168
TI  - Biomechanical analysis of prey capture in the carnivorous Southern bladderwort
      (Utricularia australis).
AB  - We recorded capture events (CEs) of the daphniid Ceriodaphnia dubia by the
      carnivorous Southern bladderwort with suction traps (Utricularia australis).
      Independent to orientation and behavior during trap triggering, the animals were
      successfully captured within 9 ms on average and sucked in with velocities of up
      to 4 m/s and accelerations of up to 2800 g. Phases of very high acceleration
      during onsets of suction were immediately followed by phases of similarly high
      deceleration (max.: -1900 g) inside the bladders, leading to immobilization of
      the prey which then dies. We found that traps perform a 'forward strike' during
      suction and that almost completely air-filled traps are still able to perform
      suction. The trigger hairs on the trapdoors can undergo strong bending
      deformation, which we interpret to be a safety feature to prevent fracture. Our
      results highlight the elaborate nature of the Utricularia suction traps which are
      functionally resilient and leave prey animals virtually no chance to escape.

PMID- 28496167
TI  - Effect of Trichoderma harzianum on maize rhizosphere microbiome and biocontrol of
      Fusarium Stalk rot.
AB  - Fusarium stalk rot (FSR) caused by Fusarium graminearum (FG) significantly
      affects the productivity of maize grain crops. Application of agrochemicals to
      control the disease is harmful to environment. In this regard, use of biocontrol
      agent (BCA) is an alternative to agrochemicals. Although Trichoderma species are
      known as BCA, the selection of host-pathogen specific Trichoderma is essential
      for the successful field application. Hence, we screened a total of 100
      Trichoderma isolates against FG, selected Trichoderma harzianum (CCTCC-RW0024)
      for greenhouse experiments and studied its effect on changes of maize rhizosphere
      microbiome and biocontrol of FSR. The strain CCTCC-RW0024 displayed high
      antagonistic activity (96.30%), disease reduction (86.66%), biocontrol-related
      enzyme and gene expression. The root colonization of the strain was confirmed by
      eGFP tagging and qRT-PCR analysis. Pyrosequencing revealed that exogenous
      inoculation of the strain in maize rhizosphere increased the plant growth
      promoting acidobacteria (18.4%), decreased 66% of FG, and also increased the
      plant growth. In addition, metabolites of this strain could interact with
      pathogenicity related transcriptional cofactor FgSWi6, thereby contributing to
      its inhibition. It is concluded that T. harzianum strain CCTCC-RW0024 is a
      potential BCA against FSR.

PMID- 28496169
TI  - Exploring the link between cadmium and psoriasis in a nationally representative
      sample.
AB  - Psoriasis, a skin inflammatory disease, originates from dysregulated interactions
      of the immune system. Cadmium, an environment pollutant, increases the levels of
      inflammation markers and influences the immune system. To clarify the
      relationship between cadmium and psoriasis, 5,927 participants, >=20 years, in
      the National Health and Nutrition Examination Survey (NHANES) 2003-2006 were
      studied. Psoriasis severity was assessed using self-reported dermatology
      questionnaires. Cadmium was measured using blood chemistry. Three adjusted models
      were applied for the interaction between serum cadmium and severity of psoriasis.
      Psoriasis patients had significantly higher blood cadmium (0.67 vs. 0.52 MUg/L, p
      = 0.006). There was a strong linear increase in predicted blood cadmium values
      with an increase in severity of psoriasis (p for trend = 0.002). The beta
      coefficient of the predicted serum cadmium in the "few patches to extensive
      psoriasis" group was 0.234 (p = 0.002) after adjusting covariates. Participants
      with severe psoriasis have higher blood cadmium. Environmental exposure to
      cadmium can predispose to the worsening of psoriasis. Although there are still
      limitations in this study, such as not included treatment data, these results
      have substantial public health implications for the general population, as they
      demonstrate the importance of cadmium exposure prevention, particularly among
      psoriasis patients.

PMID- 28496172
TI  - Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During
      Monetary Reward Anticipation in Drug and Alcohol Dependence.

PMID- 28496170
TI  - Anomalous in-plane anisotropic Raman response of monoclinic semimetal 1 T'-MoTe
      2.
AB  - The recently discovered two-dimensional (2D) semimetal 1 T'-MoTe2 exhibits
      colossal magnetoresistance and superconductivity, driving a strong research
      interest in the material's quantum phenomena. Unlike the typical hexagonal
      structure found in many 2D materials, the 1 T'-MoTe2 lattice has strong in-plane
      anisotropy. A full understanding of the anisotropy is necessary for the
      fabrication of future devices which may exploit these quantum and topological
      properties, yet a detailed study of the material's anisotropy is currently
      lacking. While angle resolved Raman spectroscopy has been used to study
      anisotropic 2D materials, such as black phosphorus, there has been no in-depth
      study of the Raman dependence of 1 T'-MoTe2 on different layer numbers and
      excitation energies. Here, our angle resolved Raman spectroscopy shows intricate
      Raman anisotropy dependences of 1 T'-MoTe2 on polarization, flake thickness (from
      single layer to bulk), photon, and phonon energies. Using a Paczek approximation,
      the anisotropic Raman response can be captured in a classical framework. Quantum
      mechanically, first-principle calculations and group theory reveal that the
      anisotropic electron-photon and electron-phonon interactions are nontrivial in
      the observed responses. This study is a crucial step to enable potential
      applications of 1 T'-MoTe2 in novel electronic and optoelectronic devices where
      the anisotropic properties might be utilized for increased functionality and
      performance.

PMID- 28496171
TI  - Altered balance of excitatory and inhibitory learning in a genetically modified
      mouse model of glutamatergic dysfunction relevant to schizophrenia.
AB  - The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in
      schizophrenia. Gria1 knockout in mice results in recently experienced stimuli
      acquiring aberrantly high salience. This suggests that GluA1 may be important for
      learning that is sensitive to the temporal contiguity between events. To test
      this, mice were trained on a Pavlovian trace conditioning procedure in which the
      presentation of an auditory cue and food were separated by a temporal interval.
      Wild-type mice initially learnt, but with prolonged training came to withhold
      responding during the trace-conditioned cue, responding less than for another cue
      that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained
      performance over training, responding more to the trace-conditioned cue than the
      nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory
      properties (signalling the absence of food) in wild-type mice, but Gria1 deletion
      impaired the acquisition of inhibition, thus maintaining the stimulus as an
      excitatory predictor of food. Furthermore, when there was no trace both groups
      showed successful learning. These results suggest that cognitive abnormalities in
      disorders like schizophrenia in which gluatamatergic signalling is implicated may
      be caused by aberrant salience leading to a change in the nature of the
      information that is encoded.

PMID- 28496173
TI  - Memories of Opiate Withdrawal Emotional States Correlate with Specific Gamma
      Oscillations in the Nucleus Accumbens.

PMID- 28496174
TI  - NPP: Our Designs for the Future.

PMID- 28496175
TI  - Thomas Hanlon.

PMID- 28496176
TI  - Efficacy and safety of thiazolidinediones in diabetes patients with renal
      impairment: a systematic review and meta-analysis.
AB  - We conducted a systematic review and meta-analysis to evaluate the efficacy and
      safety of TZDs in treatment of diabetes mellitus patients with renal impairment.
      We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials.
      Randomized controlled trials (RCTs), cohort studies, and case-control studies
      that investigated the effects of TZDs in patients with diabetes and renal
      impairment were eligible. Outcomes included glycosylated hemoglobin, fasting
      plasma glucose, serum lipids, and patient-important outcomes (i.e. hypoglycemia,
      weight, edema, cardiovascular events and mortality). 19 RCTs and 3 cohort studies
      involving 21,803 patients with diabetes and renal impairment were included. Meta
      analysis of RCTs showed that TZDs could significantly reduce HbA1c (MD -0.64,
      95%CI -0.93 to -0.35), FPG (MD -26.27, 95%CI -44.90 to -7.64) and increase HDL
      levels (MD 3.70, 95%CI 1.10, 6.29). TZDs could increase weight (MD 3.23, 95% CI
      2.29 to 4.16) and risk of edema (RR 2.96, 95% CI 1.22 to 7.20). Their effects on
      risk of hypoglycemia (RR 1.46, 95% CI 0.65 to 3.29), heart failure (RR 0.64, 95%
      CI 0.15 to 2.66), angina (RR 1.45, 95% CI 0.23 to 8.95) and all-cause mortality
      (RR 0.40, 95% CI 0.08 to 2.01) are uncertain. Results from cohort studies were
      similar to RCTs.

PMID- 28496177
TI  - Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute
      myeloid leukemia.

PMID- 28496178
TI  - Adsorption energy of oxygen molecules on graphene and two-dimensional tungsten
      disulfide.
AB  - Adsorption of gas molecules on the surface of atomically layered two-dimensional
      (2D) materials, including graphene and transition metal dichalcogenides, can
      significantly affect their electrical and optical properties. Therefore, a
      microscopic and quantitative understanding of the mechanism and dynamics of
      molecular adsorption and desorption has to be achieved in order to advance device
      applications based on these materials. However, recent theoretical calculations
      have yielded contradictory results, particularly on the magnitude of the
      adsorption energy. Here, we have experimentally determined the adsorption energy
      of oxygen molecules on graphene and 2D tungsten disulfide using temperature
      programmed terahertz (THz) emission microscopy (TPTEM). The temperature
      dependence of THz emission from InP surfaces covered with 2D materials reflects
      the change in oxygen concentration due to thermal desorption, which we used to
      estimate the adsorption energy of oxygen molecules on graphene (~0.15 eV) and
      tungsten disulphide (~0.24 eV). Furthermore, we used TPTEM to visualize relative
      changes in the spatial distribution of oxygen molecules on monolayer graphene
      during adsorption and desorption. Our results provide much insight into the
      mechanism of molecular adsorption on the surface of 2D materials, while
      introducing TPTEM as a novel and powerful tool for molecular surface science.

PMID- 28496179
TI  - Microfluidic system for monitoring temporal variations of hemorheological
      properties and platelet adhesion in LPS-injected rats.
AB  - Sepsis causes multiple organs failures and eventually death. Changes in blood
      constituents due to sepsis lead to alterations in hemorheological properties, and
      cell adhesiveness. In this study, a new microfluidic system is proposed to
      measure temporal variations in biophysical properties of blood after injecting
      lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition.
      To measure blood viscosity, the interfacial line between blood and a reference
      fluid is formed in a Y-shaped channel. Based on the relation between interfacial
      width and pressure ratio, the temporal variation in blood viscosity is estimated.
      Optical images of blood flows are analyzed by decreasing flow rate for
      examination of red blood cell (RBC) aggregation. Platelets initiated by shear
      acceleration around the stenosis adhere to the post-stenosed region. By applying
      a correlation map that visualizes the decorrelation of the streaming blood flow,
      the area of adhered platelets can be quantitatively attained without labeling of
      platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8)
      are also monitored. The increasing tendency for blood viscosity, RBC aggregation,
      platelet adhesion, and septic biomarkers are observed after LPS injection. This
      microfluidic system would be beneficial for monitoring the changes in
      hemorheological properties and platelet activation caused by sepsis.

PMID- 28496180
TI  - Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell
      lymphoma: a meta-analysis.
AB  - The precise clinicopathologic significance of myeloid differentiation primary
      response gene (MYD88) L265P mutation in diffuse large B-cell lymphomas (DLBCLs)
      remains elusive. To investigate the frequency and clinicopathologic significance
      of the MYD88 L265P mutation in DLBCLs, we conducted a meta-analysis of 40
      published studies on 2736 DLBCL patients. We collected relevant published
      research findings identified using the PubMed and Embase databases. The effect
      sizes of outcome parameters were calculated using a random-effects model. In this
      meta-analysis, the MYD88 L265P mutation in DLBCL showed a significant difference
      according to tumor sites. The overall incidence of the MYD88 L265P mutation in
      DLBCLs, excluding the central nervous system and testicular DLBCLs, was 16.5%.
      Notably, the MYD88 L265P mutation rates of CNS and testicular DLBCL patients were
      60% and 77%, respectively. Interestingly, the MYD88 L265P mutation was more
      frequently detected in activated B-cell-like (ABC) or non-germinal center B-cell
      like (GCB) than GCB subtype (OR = 3.414, p < 0.001). The MYD88 L265P mutation was
      significantly associated with old age and poor overall survival, but not with sex
      and clinical stage. This pooled analysis demonstrates that the MYD88 L265P
      mutation is significantly associated with the tumor sites and molecular subtypes
      in DLBCL patients.

PMID- 28496182
TI  - Characterization of off-odours and potentially harmful substances in a fancy
      dress accessory handbag for children.
AB  - A fancy dress accessory handbag for children was claimed by consumers to exhibit
      an offensive smell. Sensory characterization by an expert panel revealed, amongst
      others, rubber- and car tire - like notes. For elucidation of the molecular
      reasons of this sensory defect, the volatile fraction of the product was isolated
      by means of solvent extraction and high vacuum distillation. Identification of
      the main odorants was accomplished by means of one- and two-dimensional gas
      chromatography, with parallel mass spectrometric and olfactometric detection. In
      total more than 60 odorants were detected in the sample and more than 30 of these
      odour-active substances could be identified. Amongst them were a number of
      naphthalene derivatives as well as saturated and mono- or di-unsaturated carbonyl
      compounds. The naphthalene derivatives that were identified in the children's
      article appeared to be mainly responsible for the characteristic off-odour.
      Additionally, a GC-MS-screening for polycyclic aromatic hydrocarbons (PAHs) was
      performed, which revealed the presence of 15 PAHs in total. However, 14 of them
      were of no relevance for the smell of the product.

PMID- 28496181
TI  - The neuronal K+Cl- co-transporter 2 (Slc12a5) modulates insulin secretion.
AB  - Intracellular chloride concentration ([Cl-]i) in pancreatic beta-cells is kept
      above electrochemical equilibrium due to the predominant functional presence of
      Cl- loaders such as the Na+K+2Cl- co-transporter 1 (Slc12a2) over Cl-extruders of
      unidentified nature. Using molecular cloning, RT-PCR, Western blotting,
      immunolocalization and in vitro functional assays, we establish that the "neuron
      specific" K+Cl- co-transporter 2 (KCC2, Slc12a5) is expressed in several
      endocrine cells of the pancreatic islet, including glucagon secreting alpha
      cells, but particularly in insulin-secreting beta-cells, where we provide
      evidence for its role in the insulin secretory response. Three KCC2 splice
      variants were identified: the formerly described KCC2a and KCC2b along with a
      novel one lacking exon 25 (KCC2a-S25). This new variant is undetectable in brain
      or spinal cord, the only and most abundant known sources of KCC2. Inhibition of
      KCC2 activity in clonal MIN6 beta-cells increases basal and glucose-stimulated
      insulin secretion and Ca2+ uptake in the presence of glibenclamide, an inhibitor
      of the ATP-dependent potassium (KATP)-channels, thus suggesting a possible
      mechanism underlying KCC2-dependent insulin release. We propose that the long
      time considered "neuron-specific" KCC2 co-transporter is expressed in pancreatic
      islet beta-cells where it modulates Ca2+-dependent insulin secretion.

PMID- 28496183
TI  - Everyday cognition scales are related to cognitive function in the early stage of
      probable Alzheimer's disease and FDG-PET findings.
AB  - We applied the Everyday Cognition (ECog) scale in normal aging adults and
      patients with Alzheimer's disease (AD) to investigate associations between
      neuropsychological tests and neuroimaging markers. A total of 160 normal aging
      adults and 40 patients with the early stage of probable AD were included.
      Neuropsychological performance was assessed using the Consortium to Establish a
      Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD
      NAB). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans were
      used to measure AD-related hypometabolism. Nonparametric Spearman correlation
      analysis was used to study associations between ECog and z-transformed total
      CERAD-NAB scores in both groups. The results revealed a significant correlation
      between total ECog and CERAD-NAB scores (rho = -0.28, p < 0.01), and category
      verbal fluency test with the executive domain of the ECog scale (rho = -0.20, p <
      0.01). The CERAD-NAB scores were also significantly correlated with AD-related
      hypometabolism (rho = -0.49, p < 0.01). The memory domain of the ECog scale was
      significantly correlated with FDG uptake in the angular gyrus and posterior
      cingulum gyrus (rho = -0.41 and -0.46, P < 0.01). In conclusion, both total and
      memory domain ECog scores were correlated with the neuropsychological tests and
      neuroimaging biomarkers.

PMID- 28496184
TI  - El Nino increases the risk of lower Mississippi River flooding.
AB  - Mississippi River floods rank among the costliest climate-related disasters in
      the world. Improving flood predictability, preparedness, and response at seasonal
      to decadal time-scales requires an understanding of the climatic controls that
      govern flood occurrence. Linking flood occurrence to persistent modes of climate
      variability like the El Nino-Southern Oscillation (ENSO) has proven challenging,
      due in part to the limited number of high-magnitude floods available for study in
      the instrumental record. To augment the relatively short instrumental record, we
      use output from the Community Earth System Model (CESM) Last Millennium Ensemble
      (LME) to investigate the dynamical controls on discharge extremes of the lower
      Mississippi River. We show that through its regional influence on surface water
      storage, the warm phase of ENSO preconditions the lower Mississippi River to be
      vulnerable to flooding. In the 6-12 months preceding a flood, El Nino generates a
      positive precipitation anomaly over the lower Mississippi basin that gradually
      builds up soil moisture and reduces the basin's infiltration capacity, thereby
      elevating the risk of a major flood during subsequent rainstorms. Our study
      demonstrates how natural climate variability mediates the formation of extreme
      floods on one of the world's principal commercial waterways, adding significant
      predictive ability to near- and long-term forecasts of flood risk.

PMID- 28496185
TI  - 'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex
      molecular regulation.
AB  - The Gardos channel is a Ca2+ sensitive, K+ selective channel present in several
      tissues including RBCs, where it is involved in cell volume regulation. Recently,
      mutations at two different aminoacid residues in KCNN4 have been reported in
      patients with hereditary xerocytosis. We identified by whole exome sequencing a
      new family with two members affected by chronic hemolytic anemia carrying
      mutation R352H in the KCNN4 gene. No additional mutations in genes encoding for
      RBCs cytoskeletal, membrane or channel proteins were detected. We performed
      functional studies on patients' RBCs to evaluate the effects of R352H mutation on
      the cellular properties and eventually on the clinical phenotype. Gardos channel
      hyperactivation was demonstrated in circulating erythrocytes and erythroblasts
      differentiated ex-vivo from peripheral CD34+ cells. Pathological alterations in
      the function of multiple ion transport systems were observed, suggesting the
      presence of compensatory effects ultimately preventing cellular dehydration in
      patient's RBCs; moreover, flow cytometry and confocal fluorescence live-cell
      imaging showed Ca2+ overload in the RBCs of both patients and hypersensitivity of
      Ca2+ uptake by RBCs to swelling. Altogether these findings suggest that the
      'Gardos channelopathy' is a complex pathology, to some extent different from the
      common hereditary xerocytosis.

PMID- 28496186
TI  - An ancient selective sweep linked to reproductive life history evolution in
      sockeye salmon.
AB  - Study of parallel (or convergent) phenotypic evolution can provide important
      insights into processes driving sympatric, ecologically-mediated divergence and
      speciation, as ecotype pairs may provide a biological replicate of the underlying
      signals and mechanisms. Here, we provide evidence for a selective sweep creating
      an island of divergence associated with reproductive behavior in sockeye salmon
      (Oncorhynchus nerka), identifying a series of linked single nucleotide
      polymorphisms across a ~22,733 basepair region spanning the leucine-rich repeat
      containing protein 9 gene exhibiting signatures of divergent selection associated
      with stream- and shore-spawning in both anadromous and resident forms across
      their pan-Pacific distribution. This divergence likely occurred ~3.8 Mya (95% HPD
      = 2.1-6.03 Mya), after sockeye separated from pink (O. gorbuscha) and chum (O.
      keta) salmon, but prior to the Pleistocene glaciations. Our results suggest
      recurrent evolution of reproductive ecotypes across the native range of O. nerka
      is at least partially associated with divergent selection of pre-existing genetic
      variation within or linked to this region. As sockeye salmon are unique among
      Pacific salmonids in their flexibility to spawn in lake-shore benthic
      environments, this region provides great promise for continued investigation of
      the genomic basis of O. nerka life history evolution, and, more broadly, for
      increasing our understanding of the heritable basis of adaptation of complex
      traits in novel environments.

PMID- 28496187
TI  - Geometric explanation of the rich-club phenomenon in complex networks.
AB  - The rich club organization (the presence of highly connected hub core in a
      network) influences many structural and functional characteristics of networks
      including topology, the efficiency of paths and distribution of load. Despite its
      major role, the literature contains only a very limited set of models capable of
      generating networks with realistic rich club structure. One possible reason is
      that the rich club organization is a divisive property among complex networks
      which exhibit great diversity, in contrast to other metrics (e.g. diameter,
      clustering or degree distribution) which seem to behave very similarly across
      many networks. Here we propose a simple yet powerful geometry-based growing model
      which can generate realistic complex networks with high rich club diversity by
      controlling a single geometric parameter. The growing model is validated against
      the Internet, protein-protein interaction, airport and power grid networks.

PMID- 28496188
TI  - Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan.
AB  - There is an ongoing search for new tracers to optimize imaging of beta cell
      derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be
      used for targeting of these tumors. Here, we investigated whether radiolabeled
      maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally
      conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively).
      BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In
      111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan. Biodistribution studies were
      carried out at 1, 2 and 4 hours after injection and SPECT/CT imaging 1 and 4
      hours after injection of maxadilan-DTPA-111In. Radiolabeling of maxadilan-DTPA
      (680 MBq/nmol) was more efficient than of DTPA-maxadilan (55 MBq/nmol).
      Conjugation with DTPA slightly reduced receptor binding affinity in vitro: IC50
      values were 3.2, 21.0 and 21.0 nM for maxadilan, natIn-DTPA-maxadilan and
      maxadilan-DTPA-natIn respectively. Upon i.v. injection maxadilan-DTPA-111In
      accumulated specifically in INS-1 tumors (7.30 +/- 1.87%ID/g) and in the pancreas
      (3.82 +/- 0.22%ID/g). INS-1 tumors were clearly visualized by small animal
      SPECT/CT. In conclusion, this study showed that the high affinity of maxadilan to
      the PAC1 receptor was maintained after DTPA conjugation. Furthermore,
      radiolabeled maxadilan-DTPA accumulated specifically in INS-1 tumors and,
      therefore, may qualify as a useful tracer to image insulinomas.

PMID- 28496189
TI  - Impacts of carbon nanomaterials on the diversity of microarthropods in turfgrass
      soil.
AB  - Nanoscale materials have been produced with unprecedented speed due to their
      widespread use, and they may eventually be released into the environment. As
      effective adsorbents for heavy metals, carbon nanomaterials can be used to
      immobilize metals in contaminated soil, but little information is available
      regarding their effects on soil microarthropods. This study was designed to
      investigate the influence of three types of carbon nanomaterials, graphene (G),
      graphene oxide (GO) and carbon nanotubes (CNTs) on soil microarthropod
      communities under turfgrass growth conditions. The application of carbon
      nanomaterials resulted in increased abundance of all soil microarthropods,
      especially in the GO and CNT treatments. GO also significantly increased the
      abundances of multiple trophic functional groups, including predators,
      detritivores, herbivores and fungivores. Further, the dominant genera varied
      among the treatments. Herbivorous microarthropods predominated in the control,
      whereas predatory species predominated in the carbon nanomaterial treatments.
      Carbon nanomaterials also increased the total taxonomic richness, Shannon
      diversity index, and dominance index of the microarthropod community, but they
      decreased the evenness index. Higher diversity of soil microarthropods indicates
      an environment suitable for soil mesofauna and for enhanced decomposition and
      nutrient cycling in the soil food web.

PMID- 28496191
TI  - Breed, sex, and litter effects in 2-month old puppies' behaviour in a
      standardised open-field test.
AB  - A considerable number of studies have reported differences among dog breeds with
      respect to their genetic profile, cognitive abilities or personality traits. Each
      dog breed is normally treated as a homogeneous group, however, researchers have
      recently questioned whether the behavioural profile of modern breeds still
      reflects their historical function or if the intense divergent selective
      pressures and geographical barriers have created a more fragmented picture. The
      majority of studies attempting to assess and compare modern breeds' personality
      focused on the evaluation of adult dogs where the potential effects of
      environmental/human factors on the dogs' behaviour are hard to discern from their
      genetic heritage. In the following study, we aimed at investigating between- and
      within-breed differences in the personality of two-months-old puppies by direct
      behavioural observation of 377 puppies from 12 breeds. Results showed that there
      was no effect of sex, however both breed and litter, significantly affected all
      personality traits. Breed on average explained 10% of the variance, whereas the
      effect of litter was noticeably higher, explaining on average 23% of the
      variance. Taken together, our results suggest that breed does have some influence
      on personality traits, but they also highlight the importance of taking litter
      effects into account.

PMID- 28496190
TI  - Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a
      secondary analysis of data from a randomised controlled trial.
AB  - : Asthma mortality surveys report delays in seeking medical review and overuse of
      beta-agonist therapy as factors contributing to a fatal outcome. However, the
      strength of these associations is limited because many asthma deaths are
      unwitnessed. We undertook a secondary analysis of data from a 24-week randomised
      controlled trial of 303 patients with high-risk asthma, randomised to combination
      budesonide/formoterol inhaler according to a single maintenance and reliever
      therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever
      (Standard) regimen. Medication use was measured by electronic monitors. The
      thresholds for high, marked and extreme beta-agonist use days were defined in the
      single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of
      budesonide/formoterol in excess of four maintenance doses, respectively; and in
      the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively.
      Whether a medical review was obtained within 48 h of an overuse episode was
      determined by review of data collected during the study by participant report.
      The mean (standard deviation) proportion of days in which high, marked and
      extreme beta-agonist overuse occurred without medical review within 48 h was
      0.94(0.20), 0.94(0.15) and 0.94(0.17), and 0.92(0.19), 0.90(0.26) and 0.94(0.15)
      for single maintenance and reliever therapy and Standard regimens, respectively.
      In at least 90% of days, in which beta-agonist overuse occurred, patients did not
      obtain medical review within 48 h of beta-agonist overuse, regardless of the
      magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist
      regimen. RELIEVER INHALER OVERUSE AND DELAY IN MEDICAL REVIEW IN ASTHMA: In
      asthma, overuse of beta-agonist reliever medication and delay in seeking medical
      review in an exacerbation are linked to asthma deaths. Janine Pilcher at the
      Medical Research Institute of New Zealand, and co-workers, conducted a review of
      data from a study of 303 adult patients with severe asthma, followed over 24
      weeks. The patients were allocated to either a budesonide/formoterol, or a
      salbutamol inhaler to take for symptom relief, in addition to their maintenance
      treatment. Inhalers were fitted with electronic monitors, to accurately document
      every use. In both groups, on 90% of days when an exacerbation requiring excess
      use of an inhaler occurred, patients did not follow-up with medical professionals
      within 48 h as advised. Further, in both groups, 'extreme' reliever inhaler use
      was recorded at least once in around one in four patients.

PMID- 28496192
TI  - Magnetic field tuning of an excitonic insulator between the weak and strong
      coupling regimes in quantum limit graphite.
AB  - The excitonic insulator phase has long been predicted to form in proximity to a
      band gap opening in the underlying band structure. The character of the pairing
      is conjectured to crossover from weak (BCS-like) to strong coupling (BEC-like) as
      the underlying band structure is tuned from the metallic to the insulating side
      of the gap opening. Here we report the high-magnetic field phase diagram of
      graphite to exhibit just such a crossover. By way of comprehensive angle-resolved
      magnetoresistance measurements, we demonstrate that the underlying band gap
      opening occurs inside the magnetic field-induced phase, paving the way for a
      systematic study of the BCS-BEC-like crossover by means of conventional condensed
      matter probes.

PMID- 28496193
TI  - Exendin-4 Exhibits Enhanced Anti-tumor Effects in Diabetic Mice.
AB  - Type 2 diabetes (T2D) is associated with increased risk of cancers. In this
      connection, we previously demonstrated the promoting effect of diabetes on HPV
      associated carcinogenesis using a xenograft model in db/db diabetic mice. The
      underlying mechanism of this observation might be partly contributed by
      dysregulated immune response in diabetes. In this study, we hypothesized that the
      impaired anti-tumor immune response in diabetic status could be modulated by
      exendin-4, a glucagon-like protein receptor agonist which exhibits anti-diabetic
      effects. We inoculated 10-week old db/db mice with 2 * 107 CUP-1 cells (Human
      Papilloma Virus (HPV)-16 E7 transfected continuous cell line) subcutaneously
      underneath the scruff, and treated mice with high (30 nmol/kg) or low (10
      nmol/kg) dose of exendin-4 for 13 days. Compared with control groups, exendin-4
      suppressed subcutaneous tumor growth in a dose-dependent manner, accompanied by
      increased interferon (IFN)-gamma secreting CD8+ cytotoxic T lymphocyte
      (CTL)/Foxp3+ regulatory T cell (Treg) ratio as well as Th1 proinflammatory
      cytokines IFN-gamma and IL-2. Collectively, these findings suggested an anti
      tumor effect of exendin-4 in diabetic conditions, which might be resulted from
      direct immunomodulation.

PMID- 28496194
TI  - Zooplankton Community Profiling in a Eutrophic Freshwater Ecosystem-Lake Tai
      Basin by DNA Metabarcoding.
AB  - Communities of zooplankton, a critical portion of aquatic ecosystems, can be
      adversely affected by contamination resulting from human activities.
      Understanding the influence of environmental change on zooplankton communities
      under field-conditions is hindered by traditional labor-intensive approaches that
      are prone to taxonomic and enumeration mistakes. Here, metabarcoding of
      cytochrome c oxidase I (COI) region of mitochondrial DNA was used to characterize
      the genetic diversity of zooplankton. The species composition of zooplankton
      communities determined by metabarcoding was consistent with the results based on
      the traditional morphological approach. The spatial distribution of common
      species (frequency of occurrence >10 samples) by metabarcoding exhibited good
      agreement with morphological data. Furthermore, metabarcoding can clearly
      distinguish the composition of the zooplankton community between lake and river
      ecosystems. In general, rotifers were more abundant in riverine environments than
      lakes and reservoirs. Finally, the sequence read number of different taxonomic
      groups using metabarcoding was positively correlated with the zooplankton biomass
      inferred by density and body length of zooplankton. Overall, the utility of
      metabarcoding for taxonomic profiling of zooplankton communities was validated by
      the morphology-based method on a large ecological scale. Metabarcoding of COI
      could be a powerful and efficient biomonitoring tool to protect local aquatic
      ecosystems.

PMID- 28496195
TI  - Symmetry breaking during homodimeric assembly activates an E3 ubiquitin ligase.
AB  - C-terminus of Hsc/p70-Interacting Protein (CHIP) is a homodimeric E3 ubiquitin
      ligase. Each CHIP monomer consists of a tetratricopeptide-repeat (TPR), helix
      turn-helix (HH), and U-box domain. In contrast to nearly all homodimeric
      proteins, CHIP is asymmetric. To uncover the origins of asymmetry, we performed
      molecular dynamics simulations of dimer assembly. We determined that a CHIP
      monomer is most stable when the HH domain has an extended helix that supports
      intra-monomer TPR-U-box interaction, blocking the E2-binding surface of the U
      box. We also discovered that monomers first dimerize symmetrically through their
      HH domains, which then triggers U-box dimerization. This brings the extended
      helices into close proximity, including a repulsive stretch of positively charged
      residues. Unable to smoothly unwind, this conflict bends the helices until the
      helix of one protomer breaks to relieve the repulsion. The abrupt snapping of the
      helix forces the C-terminal residues of the other protomer to disrupt that
      protomer's TPR-U-box tight binding interface, swiftly exposing and activating one
      of the E2 binding sites. Mutagenesis and biochemical experiments confirm that C
      terminal residues are necessary both to maintain CHIP stability and function.
      This novel mechanism indicates how a ubiquitin ligase maintains an inactive
      monomeric form that rapidly activates only after asymmetric assembly.

PMID- 28496196
TI  - TaPIMP2, a pathogen-induced MYB protein in wheat, contributes to host resistance
      to common root rot caused by Bipolaris sorokiniana.
AB  - MYB transcription factors (TFs) have been implicated in various biology processes
      in model plants. However, functions of the great majority of MYB TFs in wheat
      (Triticum aestivum L.) have not been characterized. The soil-borne fungal
      pathogens Bipolaris sorokiniana and Rhizoctonia cerealis are the causal agents of
      important destructive diseases of wheat. Here, the TaPIMP2 gene, encoding a
      pathogen-induced MYB protein in wheat, was isolated through comparative
      transcriptomic analysis, and its defensive role was studied. TaPIMP2 was proved
      to localize in nuclei. TaPIMP2 responded in a different extent and speed upon
      infections of B. sorokiniana or R. cerealis. TaPIMP2 displayed different
      expression patterns after exogenous application of phytohormones, including
      abscisic acid, ethylene, and salicylic acid. Silencing of TaPIMP2 repressed
      resistance of wheat cultivar Yangmai 6 to B. sorokiniana, but did not alter
      resistance of wheat line CI12633 to R. cerealis. TaPIMP2 overexpression
      significantly improved resistance to B. sorokiniana rather than R. cerealis in
      transgenic wheat. Moreover, TaPIMP2 positively modulated the expression of
      pathogenesis-related genes, including PR1a, PR2, PR5, and PR10. Collectively,
      TaPIMP2 positively contributes to wheat resistance to B. sorokiniana possibly
      through regulating the expression of defense-related genes, and TaPIMP2 plays
      distinct roles in defense responses to different fungal infection.

PMID- 28496197
TI  - Helicobacter pylori-derived extracellular vesicles increased in the gastric
      juices of gastric adenocarcinoma patients and induced inflammation mainly via
      specific targeting of gastric epithelial cells.
AB  - Evidence indicates that Helicobacter pylori is the causative agent of chronic
      gastritis and perhaps gastric malignancy. Extracellular vesicles (EVs) play an
      important role in the evolutional process of malignancy due to their genetic
      material cargo. We aimed to evaluate the clinical significance and biological
      mechanism of H. pylori EVs on the pathogenesis of gastric malignancy. We
      performed 16S rDNA-based metagenomic analysis of gastric juices either from
      endoscopic or surgical patients. From each sample of gastric juices, the bacteria
      and EVs were isolated. We evaluated the role of H. pylori EVs on the development
      of gastric inflammation in vitro and in vivo. IVIS spectrum and confocal
      microscopy were used to examine the distribution of EVs. The metagenomic analyses
      of the bacteria and EVs showed that Helicobacter and Streptococcus are the two
      major bacterial genera, and they were significantly increased in abundance in
      gastric cancer (GC) patients. H. pylori EVs are spherical and contain CagA and
      VacA. They can induce the production of tumor necrosis factor-alpha, interleukin
      (IL)-6 and IL-1beta by macrophages, and IL-8 by gastric epithelial cells. Also,
      EVs induce the expression of interferon gamma, IL-17 and EV-specific
      immunoglobulin Gs in vivo in mice. EVs were shown to infiltrate and remain in the
      mouse stomach for an extended time. H. pylori EVs, which are abundant in the
      gastric juices of GC patients, can induce inflammation and possibly cancer in the
      stomach, mainly via the production of inflammatory mediators from gastric
      epithelial cells after selective uptake by the cells.

PMID- 28496198
TI  - Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation
      from multipotent bone marrow stromal cells and bone formation.
AB  - Strategies for efficient osteogenic differentiation and bone formation from stem
      cells would have clinical applications in treating nonunion fracture healing.
      Many researchers have attempted to develop adjuvants as specific stimulators of
      bone formation for therapeutic use in patients with bone resorption. Therefore,
      development of specific stimulators of bone formation has therapeutic
      significance in the treatment of osteoporosis. To date, investigations of the
      mature forms of bone morphogenetic proteins (BMPs) have focused on regulation of
      bone generation. However, we previously identified new peptides from the immature
      precursor of BMP, and further analysis of these proteins should be performed. In
      this study, we identified a new peptide called bone-forming peptide-2 (BFP-2),
      which has stronger osteogenic differentiation-promoting activity than BMP-7. BFP
      2 treatment of multipotent bone marrow stromal cells (BMSCs) induced expression
      of active alkaline phosphatase. In addition, BFP-2 enhanced CD44 and CD51
      expression levels and increased Ca2+ content in BMSCs. Moreover, radiography at 8
      weeks revealed that animals that had received transplants of BFP-2-treated BMSCs
      showed substantially increased bone formation compared with animals that had
      received BMSCs treated with BMP-7. Our findings indicate that BFP-2 may be useful
      in the development of adjuvant therapies for bone-related diseases.

PMID- 28496199
TI  - Upregulation and biological function of transmembrane protein 119 in
      osteosarcoma.
AB  - Osteosarcoma is suggested to be caused by genetic and molecular alterations that
      disrupt osteoblast differentiation. Recent studies have reported that
      transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and
      bone development. However, the level of TMEM119 expression and its roles in
      osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and
      protein expression was found to be up-regulated in osteosarcoma compared with
      normal bone cyst tissues. The level of TMEM119 protein expression was strongly
      associated with tumor size, clinical stage, distant metastasis and overall
      survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene
      Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in
      osteosarcoma tissues to be positively correlated with cell cycle, apoptosis,
      metastasis and TGF-beta signaling. We then knocked down TMEM119 expression in
      U2OS and MG63 cells using small interfering RNA, which revealed that
      downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells
      by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that
      TMEM119 knockdown significantly inhibited cell migration and invasion, and
      decreased the expression of TGF-beta pathway-related factors (BMP2, BMP7 and TGF
      beta). TGF-beta application rescued the inhibitory effects of TMEM119 knockdown
      on osteosarcoma cell migration and invasion. Further in vitro experiments with a
      TGF-beta inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that
      TMEM119 significantly promotes cell migration and invasion, partly through TGF
      beta/BMP signaling. In conclusion, our data support the notion that TMEM119
      contributes to the proliferation, migration and invasion of osteosarcoma cells,
      and functions as an oncogene in osteosarcoma.

PMID- 28496200
TI  - microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual
      specificity phosphatase 6 expression.
AB  - Acquisition of resistance to anti-cancer drugs is a significant obstacle to
      effective cancer treatment. Although several efforts have been made to overcome
      drug resistance in cancer cells, the detailed mechanisms have not been fully
      elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal
      regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5
      FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed
      that five miRNAs promoted cell survival after 5-FU treatment in human
      hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone
      expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU
      resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p
      cells were higher than those of control cells after 5-FU treatment. Ectopic
      expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p
      downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP
      (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a
      novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression
      of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these
      results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance
      by decreasing DUSP6 expression.

PMID- 28496201
TI  - Engulfment signals and the phagocytic machinery for apoptotic cell clearance.
AB  - The clearance of apoptotic cells is an essential process for tissue homeostasis.
      To this end, cells undergoing apoptosis must display engulfment signals, such as
      'find-me' and 'eat-me' signals. Engulfment signals are recognized by multiple
      types of phagocytic machinery in phagocytes, leading to prompt clearance of
      apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic
      signals to reduce immune responses against apoptotic cell-derived self-antigens.
      Here we discuss recent advances in our knowledge of engulfment signals, the
      phagocytic machinery and the signal transduction pathways for apoptotic cell
      engulfment.

PMID- 28496203
TI  - Common Variants in OPG Confer Risk to Bone Mineral Density Variation and
      Osteoporosis Fractures.
AB  - Although many common variants have been identified for bone mineral density (BMD)
      and osteoporosis fractures, all the identified risk variants could only explain a
      small portion of heritability of BMD and osteoporosis fractures. OPG belongs to
      the tumor necrosis factor receptor superfamily, which plays a crucial role in
      bone remodeling and is thus a promising candidate gene of osteoporosis. Several
      studies have explored the association of OPG variants with BMD or osteoporosis
      fractures, however, the results remain inconsistent among different populations.
      In the study, we first assessed the relationship between OPG variants and BMD or
      osteoporosis fractures in our sample size (227 subjects with postmenopausal
      osteoporosis and 189 controls), and then performed a systematic meta-analysis.
      Among the nine SNPs genotyped, rs6469804 and rs2073618 showed significant
      associations with both BMD and osteoporotic fractures, while rs3102735 was only
      associated with BMD in our samples (P < 0.05). For meta-analyses, data for a
      total of 12 SNPs were pooled (4725 patients and 37804 controls), and five SNPs,
      including rs6993813, rs6469804, rs3134070, rs2073618 and rs3102734, showed
      association with osteoporosis fractures (P < 0.05). On light of the above
      analysis, we believe that OPG is one promising susceptibility gene of BMD or
      osteoporotic fractures.

PMID- 28496202
TI  - Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate
      cells in vitro and limits caerulein-induced chronic pancreatitis in vivo.
AB  - Chronic pancreatitis (CP) is a fibro-inflammatory disease leading to pain,
      maldigestion, and pancreatic insufficiency. No therapeutic options exist due to a
      limited understanding of the biology of CP pathology. Recent findings implicate
      pancreatic stellate cells (PSC) as prominent mediators of inflammatory and
      fibrotic processes during CP. Here, we utilized primary and immortalized PSC
      obtained from mice and patients with CP or pancreatic cancer to examine the
      effect of Jak/STAT and MAPK pathway inhibition in vitro. The well-characterized
      caerulein model of CP was used to assess the therapeutic efficacy of Jak1/2
      inhibition in vivo. Treatment of cultured PSC with the Jak1/2 inhibitor
      ruxolitinib reduced STAT3 phosphorylation, cell proliferation, and expression of
      alpha-smooth muscle actin (alpha-SMA), a marker of PSC activation. Treatment with
      the MAPK inhibitor, MEK162, had less consistent effects on PSC proliferation and
      no impact on activation. In the caerulein-induced murine model of CP,
      administration of ruxolitinib for one week significantly reduced biomarkers of
      inflammation and fibrosis. These data suggest that the Jak/STAT pathway plays a
      prominent role in PSC proliferation and activation. In vivo treatment with the
      Jak1/2 inhibitor ruxolitinib reduced the severity of experimental CP, suggesting
      that targeting Jak/STAT signaling may represent a promising therapeutic strategy
      for CP.

PMID- 28496204
TI  - A Photochemical Avenue to Photoluminescent N-Dots and their Upconversion Cell
      Imaging.
AB  - A photochemical avenue to synthesize nitrogen-rich quantum dots (N-dots) using 2
      azido imidazole as the starting material was established for the first time. A
      production yield of up to 92.7% was obtained. The N-dots were then fully
      characterized by elemental analysis, IR, XPS, XRD, AFM and TEM. On the basis of
      the N2 production and in situ IR results, the underlying mechanism for the
      photochemical formation of N-dots was proposed. These N-dots showed promising
      optical properties including wavelength-dependent upconversion photoluminescence,
      and were successfully used in upconversion cell imaging.

PMID- 28496205
TI  - Characterisation of a 3-hydroxypropionic acid-inducible system from Pseudomonas
      putida for orthogonal gene expression control in Escherichia coli and Cupriavidus
      necator.
AB  - 3-hydroxypropionic acid (3-HP) is an important platform chemical used as a
      precursor for production of added-value compounds such as acrylic acid.
      Metabolically engineered yeast, Escherichia coli, cyanobacteria and other
      microorganisms have been developed for the biosynthesis of 3-HP. Attempts to
      overproduce this compound in recombinant Pseudomonas denitrificans revealed that
      3-HP is consumed by this microorganism using the catabolic enzymes encoded by
      genes hpdH, hbdH and mmsA. 3-HP-inducible systems controlling the expression of
      these genes have been predicted in proteobacteria and actinobacteria. In this
      study, we identify and characterise 3-HP-inducible promoters and their
      corresponding LysR-type transcriptional regulators from Pseudomonas putida
      KT2440. A newly-developed modular reporter system proved possible to demonstrate
      that PpMmsR/P mmsA and PpHpdR/P hpdH are orthogonal and highly inducible by 3-HP
      in E. coli (12.3- and 23.3-fold, respectively) and Cupriavidus necator (51.5- and
      516.6-fold, respectively). Bioinformatics and mutagenesis analyses revealed a
      conserved 40-nucleotide sequence in the hpdH promoter, which plays a key role in
      HpdR-mediated transcription activation. We investigate the kinetics and dynamics
      of the PpHpdR/P hpdH switchable system in response to 3-HP and show that it is
      also induced by both enantiomers of 3-hydroxybutyrate. These findings pave the
      way for use of the 3-HP-inducible system in synthetic biology and biotechnology
      applications.

PMID- 28496206
TI  - WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARgamma
      activity.
AB  - WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a
      member of the CCN family able to mediate cell growth, transformation and survival
      in a tissue-specific manner. Here, we report that WISP1 expression was highly
      increased in preadipocytes and decreased during adipocyte differentiation.
      Moreover, we observed an increase in WISP1 gene expression in adipose tissue from
      both diet-induced and leptin-deficient ob/ob obese mice, suggesting that WISP1
      could be involved in the pathophysiological onset of obesity. Interestingly,
      overexpression of WISP1 in 3T3-F442A cells prevented adipocyte differentiation
      via downregulation of peroxisome proliferator-activated receptor (PPARgamma)
      transcriptional activity thereby attenuating the expression of adipogenic
      markers. Conversely, silencing of WISP1 enhanced adipocyte differentiation. We
      further show that the inactivation of PPARgamma transcriptional activity was
      mediated, at least in part, by a direct physical association between WISP1 and
      PPARgamma, followed by proteasome-dependent degradation of PPARgamma. These
      results suggest for the first time that WISP1 interacts with PPARgamma and that
      this interaction results in the inhibition of PPARgamma activity. Taken together
      our results suggest that WISP1 functions as a negative regulator of adipogenesis.

PMID- 28496207
TI  - Selective doping of Ni2+ in highly transparent glass-ceramics containing nano
      spinels ZnGa2O4 and Zn1+x Ga2-2x Ge x O4 for broadband near-infrared fiber
      amplifiers.
AB  - Selective doping of Ni2+ in octahedral sites provided by nanocrystals embedded in
      glass-ceramics (GCs) is crucial to the enhancement of broadband near-infrared
      (NIR) emission. In this work, a NIR emission with a full-width-at-half-maximum
      (FWHM) of 288 nm is first reported from ZnGa2O4: Ni2+ nano-spinels embedded GCs
      with excellent transparency. A comparison is made of the NIR luminescence
      properties of Ni2+ doped GCs containing ZnGa2O4, germanium-substituted ZnGa2O4
      nano-spinels (Zn1+x Ga2-2x Ge x O4), and Zn2GeO4/Li2Ge4O9 composite nanocrystals
      that are free of Ga3+. The results show that ZnGa2O4: Ni2+ GCs exhibit a
      significantly enhanced NIR emission. The incorporation of the nucleating agent
      TiO2 is favored in terms of the increased luminescence intensity and prolonged
      lifetime. The possible causes for the enhancement effect are identified from the
      crystal structure/defects viewpoint. The newly developed GCs incorporate good
      reproducibility to allow for a tolerance of thermal treatment temperature and
      hence hold great potential of fiberization via the recently proposed "melt-in
      tube" method. They can be considered as promising candidates for broadband fiber
      amplifiers.

PMID- 28496208
TI  - Ethylenation of aldehydes to 3-propanal, propanol and propanoic acid derivatives.
AB  - Methodology has been developed for the synthesis of 3-propanaldehydes through a
      five-step process in 11-67% yield from aldehydes. Aldehydes were reacted with
      Meldrum's acid through a Knoevenagel condensation to give materials that upon
      reduction with sodium borohydride and subsequent hydrolysis decarboxylation
      generated the corresponding 3-propanoic acid derivatives. The -propanoic acid
      derivatives were reduced to give 3-propanol derivatives, which were readily
      oxidised to target 3-propanal derivatives.

PMID- 28496209
TI  - Single-cell pH imaging and detection for pH profiling and label-free rapid
      identification of cancer-cells.
AB  - Single-cell pH-sensing and accurate detection and label-free fast identification
      of cancer-cells are two long-standing pursuits in cell and life science, as
      intracellular pH plays a crucial role in many cellular events and fates, while
      the latter is vital for early cancer theranostics. Numerous methods based on
      functionalized nanoparticles and fluorescence probes have been developed for cell
      pH-sensing, but are often hindered for single-cell studies by their main
      drawbacks of complicated probe preparation and labeling, low sensitivity and poor
      reproducibility. Here we report a simple and reliable method for single-cell pH
      imaging and sensing by innovative combined use of UV-Vis microspectroscopy and
      common pH indicators. Accurate and sensitive pH detection on single-cell or sub
      cell level with good reproducibility is achieved by the method, which enables
      facile single-cell pH profiling and label-free rapid identification of cancer
      cells (due to distinguishable intracellular pH levels) for early cancer
      diagnosis, and may open a new avenue for pH-related single-cell studies.

PMID- 28496210
TI  - The caterpillar fungus, Ophiocordyceps sinensis, genome provides insights into
      highland adaptation of fungal pathogenicity.
AB  - To understand the potential genetic basis of highland adaptation of fungal
      pathogenicity, we present here the ~116 Mb de novo assembled high-quality genome
      of Ophiocordyceps sinensis endemic to the Qinghai-Tibetan Plateau. Compared with
      other plain-dwelling fungi, we find about 3.4-fold inflation of the O. sinensis
      genome due to a rapid amplification of long terminal repeat retrotransposons that
      occurred ~38 million years ago in concert with the uplift of the plateau. We also
      observe massive removal of thousands of genes related to the transport process
      and energy metabolism. O. sinensis displays considerable lineage-specific
      expansion of gene families functionally enriched in the adaptability of low
      temperature of cold tolerance, fungal pathogenicity and specialized host
      infection. We detect signals of positive selection for genes involved in
      peroxidase and hypoxia to enable its highland adaptation. Resequencing and
      analyzing 31 whole genomes of O. sinensis, representing nearly all of its
      geographic range, exhibits latitude-based population divergence and nature
      selection for population inhabitation towards higher altitudes on the Qinghai
      Tibetan Plateau.

PMID- 28496211
TI  - How to design a randomised controlled trial.
AB  - This practical paper explains how to design an randomised controlled trial (RCT)
      for those who have little prior knowledge of the topic. It covers the basics of
      radomisation, statistical testing, sample size caluclations, bias and the role of
      Clinical Trial Units.

PMID- 28496217
TI  - Fear of the dentist.
AB  - The oral health of individuals with dental phobia: a multivariate analysis of the
      Adult Dental Health Survey, 2009.

PMID- 28496215
TI  - Consent - an update.
AB  - Following the judgement in Montgomery in March 2015 which brought the law of
      consent up to speed with what the GDC 's ethical and professional guidance
      expected registrants to do, this article looks at how other cases have
      interpreted Montgomery subsequently and the impact and implications for dentists.
      The importance of excellent communication is emphasised in order to provide
      sufficient and relevant information to the particular patient you have sitting in
      your dental chair.

PMID- 28496218
TI  - Case report: Giant cell arteritis warning.

PMID- 28496219
TI  - The Flipped Classroom for pre-clinical dental skills teaching - a reflective
      commentary.
AB  - A Flipped Classroom method for teaching of adult practical pre-clinical dental
      skills was introduced to the BDS curriculum in Glasgow during the 2015/2016
      academic session. This report provides a commentary of the first year of
      employing this method - from the identification of the need to optimise teaching
      resources, through the planning, implementation and development of the method,
      with an early indication of performance.

PMID- 28496221
TI  - Is the novelty wearing off?
AB  - Investigation of the erosive potential of sour novelty sweets.

PMID- 28496220
TI  - Using a situational judgement test for selection into dental core training: a
      preliminary analysis.
AB  - Objective and setting This paper describes the evaluation of a pilot situational
      judgement test (SJT) for selection into UK Dental Core Training (DCT). The SJT's
      psychometric properties, group differences based on gender and ethnicity, and
      candidate reactions were assessed.Methods The SJT targets four non-academic
      attributes important for success in DCT. Data were collected alongside live
      selection processes from five Health Education England local teams in the UK (N =
      386). Candidates completed the pilot SJT and an evaluation questionnaire to
      examine their reactions to the test.Results SJT scores were relatively normally
      distributed and showed acceptable levels of internal reliability (alpha = 0.68).
      Difficulty level and partial correlations between scenarios and SJT total score
      were in the expected ranges (64.61% to 90.03% and r = 0.06 to 0.41,
      respectively). No group differences were found for gender, and group differences
      between White and BME candidates were minimal. Most candidates perceived the SJT
      as relevant to the target role, appropriate and fair.Conclusions This study
      demonstrated the potential suitability of an SJT for use in DCT selection. Future
      research should replicate these preliminary findings in other cohorts, and assess
      the predictive validity of the SJT for predicting key training and practice-based
      outcomes.

PMID- 28496222
TI  - EFP launch European Gum Health Day 2017 in Spain.

PMID- 28496224
TI  - Case report: Odontalgia and facial pain.

PMID- 28496225
TI  - Altmetric analysis of 2015 dental literature: a cross sectional survey.
AB  - Introduction To report and analyse Altmetric data of all dental articles and
      journals in 2015.Methods To identify all 2015 dental articles, PubMed was
      searched via Altmetric platform using the following query: ("2015/1/1"[PDAT]:
      "2015/12/31"[PDAT]) AND jsubsetd[text] NOT 2016[PDAT] on November 12, 2016.
      Altmetric data of all 2015 dental articles and journals were extracted and
      analysed by Microsoft Office Excel 2016 using descriptive statistics, graphs and
      trend-line analysis. To find the most important and influential Altmetric
      factors, multi-layered perceptron artificial neural network was employed using
      SPSS 22.Results A total of 14,884 dental articles published in 2015 using PubMed
      database were found, from which 5,153 (34.62%) articles had an Altmetric score.
      The mean Altmetric score was 2.94 +/- 9.2 (95% C.I:2.703.22). Mendeley readers
      (73.19%), Twitter (21.48%), Facebook walls (3.67%), news outlets (0.69%) and
      bloggers (0.57%) were the most popular Altmetric data resources. At journal
      level, 147 dental journals with valid Altmetric data were included in the study.
      The British Dental Journal had the first rank, followed by Journal of Dental
      Research, Journal of Clinical Periodontology and Journal of the American Dental
      Association. Sensitivity analysis showed news outlets, tweeters and scientific
      bloggers were the most important and influential Altmetric data
      resources.Discussion In comparison with all science subjects and medical and
      health sciences, 2015 Altmetric scores in dentistry were very low. Uses of new
      and emerging scholarly tools such as social media, scientific blogs and post
      publication peer-review were not common in the dental science. This negligence
      may be due to lack of knowledge and attitude. An Altmetric score is dynamic and
      may fluctuate over time.

PMID- 28496226
TI  - Oral cancer: Early/delayed diagnosis.

PMID- 28496227
TI  - Who regulates the regulator?

PMID- 28496228
TI  - Roy Storer.

PMID- 28496230
TI  - Invasive cervical resorption and the oro-facial cleft patient: a review and case
      series.
AB  - Introduction Invasive cervical resorption (ICR) has an unknown aetiology, yet it
      exhibits very aggressive behaviour compared with typical external root
      resorption, posing a high risk of tooth loss.Aim To investigate the number of
      patients at the Dublin Cleft Prosthodontic Department with an oro-facial cleft
      who experienced ICR and to identify any possible aetiological factors.Materials
      and method A retrospective investigation of all oro-facial cleft patients treated
      at the Dublin Cleft Prosthodontic Department, St James's Hospital, Dublin. All
      patients' clinical and radiological records were reviewed. Patients where tooth
      loss became inevitable due to Class 4 ICR were analysed.Results From 588 oro
      facial cleft patients, 14 (2.38%) patients with ICR were identified. Of these
      eight (57%) were female and six (43%) were male. Mean age at diagnosis was 28
      years (range = 16-49 years). Cleft type: six (42.1%) unilateral cleft lip and
      palate, eight (57.9%) bilateral cleft lip and palate. Seventeen ICR affected
      teeth in total, with eleven (65%) maxillary central incisors, two (12%) maxillary
      lateral incisors, four (23%) maxillary canines, and one (7%) central, lateral and
      canine affected. Some, (N = 10, 71.4%) presented with ICR resulting in immediate
      tooth loss. Other patients (N = 4, 28.6%) developed ICR during or following
      prosthodontic treatment at the Cleft Centre. Tooth loss for this cohort, though
      not immediate, was inevitable. All had undergone fixed orthodontic appliance
      treatment and twelve had received dento-alveolar bone grafts. A number (N = 7,
      50%) had undergone osteotomy, two (14%) had received night guard vital dental
      whitening and one had a history of trauma.Conclusions ICR, given its aggressive
      nature and ill-understood aetiology, poses significant treatment challenges. The
      most severe form of ICR (Class 4) leads inevitably to tooth loss. The slow
      moderate progression of ICR may explain the late presentation found in this
      study, reinforcing the importance of long-term follow-up of this special dental
      care group.

PMID- 28496231
TI  - Comparing the profile of child patients attending dental general anaesthesia and
      conscious sedation services.
AB  - Aims To compare the profile of paediatric patients receiving dental treatment
      under general anaesthesia (GA) or conscious sedation (CS). A second aim was to
      explore whether there is an overlap between the two patient groups.Design This
      service evaluation study was based on sociodemographic and clinical data
      extracted from clinical records of patients attending dental appointments for GA
      or CS services at King's College Hospital. Sociodemographic and clinical
      differences between GA and CS groups were explored using logistic regression
      models.Results Data from 113 children (58 GA and 55 CS) were analysed. There were
      differences between groups in terms of age and numbers of quadrants and teeth
      treated, but not in terms of sex, ethnicity or deprivation scores. In the
      adjusted model, older children and those having more teeth treated were more
      likely to be in the GA than in the CS group. An overlap between the GA and CS
      groups was found, with 50% of children aged four to nine years having two to four
      teeth treated in both groups.Conclusion Age and number of teeth treated were the
      main characteristics associated with receiving care under GA or CS. Some overlap
      between children receiving dental treatment under GA or CS existed despite
      demographic and clinical differences between both groups.

PMID- 28496232
TI  - Mystery object: Denture drop.

PMID- 28496234
TI  - Water fluoridation: It really is this simple.

PMID- 28496235
TI  - Dentists fully support HPV jabs for boys.

PMID- 28496238
TI  - OMFS: Dental fitness prior to cardiac surgery.

PMID- 28496239
TI  - Dental practice: Loyal and caring staff.

PMID- 28496244
TI  - Systematic review and meta-analysis of randomised controlled trials on the
      effectiveness of school-based dental screening versus no screening on improving
      oral health in children.
AB  - No effect of school-based dental screening programmes on caries or dental
      attendance.

PMID- 28496240
TI  - Beyond ONJ - A review of the potential uses of bisphosphonates in dentistry.
AB  - There is evidence, although limited, for beneficial effects of bisphophonates
      (BPs) across multiple dental specialties. Within implant dentistry BP coatings
      have been shown to significantly increase pull out forces and bone density in
      animal models, and significantly increase implant stability whilst reducing
      marginal bone loss in humans. Adjunctive topical and systemic application of BPs
      during conventional periodontal treatment have shown significant improvements in
      probing depth and clinical attachment level in various forms of periodontal
      disease. Within orthodontics, BPs have been shown to significantly reduce root
      resorption and have benefits with respect to anchorage maintenance. Case reports
      have suggested the use of BPs in the management of diffuse sclerosing
      osteomylitis. Whilst this review highlights these potential benefits and
      acknowledges there are no reported cases of osteonecrosis of the jaw associated
      with locally applied BP, there remains a paucity of human and long-term studies
      exploring BPs in the context of significant clinical benefit. Further human
      studies are required to understand the long-term clinical outcomes of these drugs
      when used as primary therapeutic agents, or adjuncts to conventional treatment.

PMID- 28496246
TI  - Harold Andreas Priestland.

PMID- 28496248
TI  - Fluoride varnish: our only hope?
AB  - Outcomes and costs of pre-school and school-based fluoride varnish pilots.

PMID- 28496250
TI  - First Chinese student in Plymouth as part of dental partnership.

PMID- 28496251
TI  - The management of cracked tooth syndrome in dental practice.
AB  - Cracked tooth syndrome is a commonly encountered condition in dental practice
      which frequently causes diagnostic and management challenges. This paper provides
      an overview of the diagnosis of this condition and goes on to discuss current
      short and long-term management strategies applicable to dental practitioners.
      This paper also covers the diagnosis and management of this common condition and
      aims to inform clinicians of the current thinking, as well as to provide an
      overview of the techniques commonly used in managing cracked tooth syndrome.

PMID- 28496253
TI  - Survey on the use of CAD-CAM technology by UK and Irish dental technicians.
AB  - Statement of the problem Digital workflows (CAD/CAM) have been introduced in
      dentistry during recent years. No published information exists on dental
      technicians' use and reporting of this technology.Purpose The aim of this cross
      sectional survey was to identify the extent digital technology has infiltrated
      the workplace and to investigate the factors affecting the use of CAD-CAM
      technology by dental laboratory technicians within Ireland and the UK.Materials
      and methods A web-based questionnaire was composed (Opinio, Object Planet Inc.
      Oslo, Norway) and distributed to UK and Irish dental technicians. Answers to all
      questions were anonymous and grouped such that general information was gathered
      initially, followed by branching of the survey into two sections depending on
      whether or not the respondent worked with CAD-CAM technology. Results were
      compiled and statistical analysis (Fisher's Exact test, SPSS, IBM, Armonk, New
      York, USA) was performed in order to investigate any correlation between various
      demographic variables and the answers provided.Results The survey was distributed
      to 760 UK technicians and 77 Irish technicians. The total number of completed
      surveys was 105, which yielded a total response rate of 14%. Most technicians
      reported using some form of CAD/CAM aspect in the workflow, and this was more
      significant for technicians working in large laboratories. Most training received
      was company-led. Large laboratories were also significantly correlated with less
      outsourcing of CAD/CAM work and a change in dental material use leading to the
      increase of zirconia and the decrease of noble alloys. Dental technicians did not
      report any significant change in working relationships and staffing as a result
      of CAD/CAM incorporation. High initial investment cost was the most common reason
      quoted from non-users, along with the lack of such technology in their working
      environment.

PMID- 28496255
TI  - Enhanced skills in periodontology: evaluation of a pilot scheme for general
      dental practitioners and dental care professionals in London.
AB  - Background The need for periodontal management is great and increasing; thus, the
      oral and dental workforce should be suitably equipped to deliver contemporary
      care. Health Education London developed a training scheme to extend the skills of
      dentists and dental care professionals (DCPs).Aim To examine the feasibility of
      assessing a skill-mix initiative established to enhance skills in clinical
      periodontology involving the views of patients, clinicians and key stakeholders,
      together with clinical and patient outcomes in London.Methods This mixed methods
      feasibility and pilot study involved four parallel elements: a postal
      questionnaire survey of patients; analysis of clinical logbooks; self-completion
      questionnaire survey of clinicians; and semi-structured interviews of key
      stakeholders, including clinicians.Results Twelve of the 19 clinicians
      participated in the evaluation, returning completed questionnaires (63%) and
      providing access to log diaries and patients. Periodontal data from 42 log-diary
      cases (1,103 teeth) revealed significant improvement in clinical outcomes (P =
      0.001 for all). Eighty-four percent (N = 99) of the 142 patients returning a
      questionnaire reported improved dental health; however, responses from hospital
      patients greatly exceeded those from dental practice. Interviews (N = 22)
      provided evidence that the programme contributed to professional healthcare
      across four key domains: 'service', 'quality care', 'professional' and
      'educational'. Clinicians, while supportive of the concept, raised concerns
      regarding the mismatch of their expectations and its educational and service
      outcomes.Discussion The findings suggest that it is feasible to deliver and
      evaluate inter-professional extended skills training for dentists and dental care
      professionals, and this may be evaluated using mixed methods to examine outcomes
      including clinical log diaries, patient questionnaires and stakeholder
      interviews. This inter-professional course represents a positive development for
      patient care using the expertise of different members of the dental team;
      however, its formal integration to the health and educational sectors require
      further consideration.

PMID- 28496257
TI  - Case report: Osteonecrosis as a complication of GA.

PMID- 28496258
TI  - A systematic review of the survival and complication rates of inlayretained fixed
      dental prostheses.
AB  - Difficult to make any clear recommendations, as many combinations of mechanical
      and biological characteristics may contribute to the survival of such
      restorations.

PMID- 28496261
TI  - Making Students' Thinking Visible During Active Learning.

PMID- 28496260
TI  - Overexpression of a cytochrome P450 and a UDP-glycosyltransferase is associated
      with imidacloprid resistance in the Colorado potato beetle, Leptinotarsa
      decemlineata.
AB  - Current control of insect pests relies on chemical insecticides, however,
      insecticide resistance development by pests is a growing concern in pest
      management. The main mechanisms for insecticide resistance typically involve
      elevated activity of detoxifying enzymes and xenobiotic transporters that break
      down and excrete insecticide molecules. In this study, we investigated the
      molecular mechanisms of imidacloprid resistance in the Colorado potato beetle,
      Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), an insect pest
      notorious for its capacity to develop insecticide resistance rapidly. We compared
      the transcriptome profiles of imidacloprid-resistant and sensitive beetle strains
      and identified 102 differentially expressed transcripts encoding detoxifying
      enzymes and xenobiotic transporters. Of these, 74 were up-regulated and 28 were
      down-regulated in the resistant strain. We then used RNA interference to knock
      down the transcript levels of seven up-regulated genes in the resistant beetles.
      Ingestion of double-stranded RNA successfully knocked down the expression of the
      genes for three cytochrome P450s (CYP6BQ15, CYP4Q3 and CYP4Q7), one ATP binding
      cassette (ABC) transporter (ABC-G), one esterase (EST1), and two UDP
      glycosyltransferases (UGT1 and UGT2). Further, we demonstrated that silencing of
      CYP4Q3 and UGT2 significantly increased susceptibility of resistant beetles to
      imidacloprid, indicating that overexpression of these two genes contributes to
      imidacloprid resistance in this resistant strain.

PMID- 28496262
TI  - Recruiting the Right Students.

PMID- 28496263
TI  - Lessons From a Recovering Department Chair.

PMID- 28496264
TI  - Current and Future Opportunities and Challenges in Continuing Pharmacy Education.
AB  - The Accreditation Council for Pharmacy Education (ACPE) convened a consensus
      seeking invitational conference on October 29-30, 2015, in Chicago, Ill. ACPE's
      desire to have stakeholder guidance on its role in the future of continuing
      pharmacy education and continuing professional development led to the convening
      of the conference. The purpose of this article is to summarize the proceedings of
      the conference, including the recommendations from the stakeholders.

PMID- 28496265
TI  - A Pharmacotherapy Capstone Course to Target Student Learning and Programmatic
      Curricular Assessment.
AB  - Objective. To describe how a pharmacotherapy capstone course was used for student
      learning and programmatic curricular assessment. Design. A pharmacotherapy
      capstone course was included in the University of Colorado curriculum for 13
      years from 2002 through 2014. This 9-credit hour course was the last course prior
      to Advanced Pharmacy Practice Experiences (APPEs). Students were held accountable
      for prior learning using complex patient cases and other activities that are seen
      in APPEs. Application of knowledge, skills, and critical thinking were integrated
      in this course using exclusively active learning methodologies. Students were
      expected to actively participate and learn independently, from peers and through
      self-assessment. Assessment. Evidence of student learning was demonstrated based
      on student performance on written and verbal evaluations analyzed from 2012 to
      2014. Survey and self-evaluation data indicated that students learned within the
      course. An increase in student confidence in critical thinking, problem-solving,
      decision making, and lifelong learning was also seen during APPEs. Student
      performance in this course prompted changes to prerequisite courses and guided
      development of a renewed curriculum. Conclusion. The University of Colorado
      pharmacotherapy capstone course prepared students for the rigor of APPEs,
      provided insight that facilitated improvements in prerequisite courses, and was a
      nexus for the development of a renewed curriculum, which includes a new clinical
      capstone course.

PMID- 28496267
TI  - Performance and Perceptions of Student Teams Created and Stratified Based on
      Academic Abilities.
AB  - Objective. To compare student performance, elements of peer evaluation and
      satisfaction of teams created according to students' course entrance grade point
      average (GPA). Methods. Two course sections were divided into teams of four to
      five students utilizing Comprehensive Assessment of Team Member Effectiveness
      (CATME) software. Results. Of 336 students enrolled, 324 consented to
      participation. Weekly team quiz averages were 99.1% (higher GPA), 97.2% (lower
      GPA), 97.7% (mixed GPA). Weekly individual quiz averages were 87.2% (higher GPA),
      83.3% (lower GPA), 85.2% (mixed GPA). Students with same GPA performed similarly
      individually independent of team assignment. Satisfaction ranged from 4.52
      (higher GPA), 4.73 (lower GPA), 4.53 (mixed GPA). Conclusion. Academically
      stronger students in mixed GPA teams appeared to be at a slight disadvantage
      compared to similar students in higher GPA teams. There was no difference in team
      performance for academically weaker students in lower GPA versus mixed GPA teams.
      Team satisfaction was higher in lower GPA teams.

PMID- 28496266
TI  - Computer-Assisted Decision Support for Student Admissions Based on Their
      Predicted Academic Performance.
AB  - Objective. To develop predictive computational models forecasting the academic
      performance of students in the didactic-rich portion of a doctor of pharmacy
      (PharmD) curriculum as admission-assisting tools. Methods. All PharmD candidates
      over three admission cycles were divided into two groups: those who completed the
      PharmD program with a GPA >= 3; and the remaining candidates. Random Forest
      machine learning technique was used to develop a binary classification model
      based on 11 pre-admission parameters. Results. Robust and externally predictive
      models were developed that had particularly high overall accuracy of 77% for
      candidates with high or low academic performance. These multivariate models were
      highly accurate in predicting these groups to those obtained using undergraduate
      GPA and composite PCAT scores only. Conclusion. The models developed in this
      study can be used to improve the admission process as preliminary filters and
      thus quickly identify candidates who are likely to be successful in the PharmD
      curriculum.

PMID- 28496268
TI  - Effect of a Dedicated Pharmacy Student Summer Research Program on Publication
      Rate.
AB  - Objectives. This study investigated the impact of an optional 12-week summer
      research program on the publication outcomes and satisfaction with the required
      research projects of doctor of pharmacy (PharmD) students at the Skaggs School of
      Pharmacy and Pharmaceutical Sciences (SSPPS) at the University of California San
      Diego. Methods. PubMed and Google searches provided student publications, and
      satisfaction surveys submitted by students provided their perceptions of the
      research project value. Results. Of the studied cohort, the 130 students who
      fulfilled the requirement through the optional summer research program provided
      61 full-text manuscripts and 113 abstracts. The 305 students who chose the
      standard pathway provided 35 full-text manuscripts and 34 abstracts. Students in
      both pathways agreed or strongly agreed that the research project was a valuable
      experience. Conclusions. The 12-week intensive summer research program improved
      the publication rate of pharmacy students and provided a high overall
      satisfaction with this independent learning experience.

PMID- 28496269
TI  - Best Practices for Use of Blended Learning.
AB  - Objective. To determine instructional best practice recommendations for use of
      blended learning from the students' perspective. Methods. Three focus groups were
      created, one for each of the first three years at a school of pharmacy. The focus
      group discussions were audio recorded and transcribed for content analysis.
      Results. Ten instructional best practices were identified from the focus groups:
      setting the stage, consistency when team teaching, timeliness in posting
      materials, time on task, accountability for online activities, use of structured
      active learning, instructor use of feedback on student preparation, incorporation
      of student feedback into the course, short reviews of online material during
      class, and ensuring technologies are user friendly. Conclusion. Instructors using
      blended learning should consider incorporating these best practices into their
      course design and management. More evaluation is needed to see if implementation
      of these practices affects student performance.

PMID- 28496270
TI  - Exercise as a Stress Coping Mechanism in a Pharmacy Student Population.
AB  - Objective. To assess the coping mechanisms used by pharmacy students and their
      relationship to perceived stress. Methods. Data were gathered utilizing the
      Perceived Stress Scale (PSS10) and Brief COPE with the additional coping
      mechanisms of exercise and use of prescribed medications. Results. A survey that
      was sent to 368 students had an 81% response rate. Perceived stress was
      significantly higher than standard populations, but consistent with other
      pharmacy student populations. The most frequently reported coping mechanisms were
      the adaptive strategies of active coping, acceptance and planning. Maladaptive
      strategies of behavioral disengagement, venting and self-blame were significantly
      associated with higher perceived stress scores and the new addition of an
      exercise coping mechanism significantly associated with lower perceived stress
      scores. Use of prescribed medications was not significantly associated with
      perceived stress levels. Conclusion. Inclusion of exercise as a coping mechanism
      may be beneficial in similar populations.

PMID- 28496271
TI  - An Analysis of Quality Improvement Education at US Colleges of Pharmacy.
AB  - Objective. Analyze quality improvement (QI) education across US pharmacy
      programs. Methods. This was a two stage cross-sectional study that inspected each
      accredited school website for published QI curriculum or related content, and e
      mailed a questionnaire to each school asking about QI curriculum or content. T
      test and chi square were used for analysis with an alpha a priori set at .05.
      Results. Sixty responses (47% response rate) revealed the least-covered QI
      topics: quality dashboards /sentinel systems (30%); six-sigma or other QI
      methodologies (45%); safety and quality measures (57%); Medicare Star measures
      and payment incentives (58%); and how to implement changes to improve quality
      (60%). More private institutions covered Adverse Drug Events than public
      institutions and required a dedicated QI class; however, required QI projects
      were more often reported by public institutions. Conclusion. Despite the need for
      pharmacists to understand QI, it is not covered well in school curricula.

PMID- 28496272
TI  - Evaluation of a Longitudinal Advanced Pharmacy Practice Experience.
AB  - Objective. To describe satisfaction and career path of students who participated
      in the longitudinal advanced pharmacy practice experience (APPE). Methods. A 3
      part survey was administered to students enrolled between January 1, 2010, and
      December 31, 2013. The sections of the survey evaluated respondents' baseline
      characteristics, satisfaction, and career path. Results. Majority of the
      respondents had a GPA above 3.0 (91%), pharmacy school honors (84%), work
      experience in retail (16%) or multiple pharmacy sites (38%), and were members of
      at least one professional organization (76%). Sixty-nine percent reported that
      the program exceeded their expectations. Strengths included practice site
      consistency, rotation diversity, preceptors, presentations, and collaboration
      with health care professionals. Students gained approximately 76 hours of
      additional clinical experience, compared to if they completed rotations at
      individual sites. After graduation, more than half of the respondents accepted a
      pharmacy practice residency (67%). Conclusion. The results of this study support
      the need for APPE programs that prepare students to deliver advanced patient
      care, while providing them with professional development.

PMID- 28496273
TI  - Predictive Relationships Between Students' Evaluation Ratings and Course
      Satisfaction.
AB  - Objective. To assess the reliability and validity of course evaluation data.
      Methods. A correlation study was conducted using archival data from pharmacy
      student course evaluations. Bivariate relationships between eight course-rating
      items and overall rating item and the extent to which course type, level, and
      grade point average moderated these relationships were analyzed. Results.
      Significant bivariate relationships were found between the eight course
      evaluation rating variables and the overall course rating variable. Pharmacy
      practice course type significantly moderated the relationship between all
      predictor and criterion variables. Conclusion. Pharmacy school administrators
      should consider individual course evaluation item ratings when making decisions
      regarding course offerings or faculty promotion and tenure.

PMID- 28496274
TI  - Student Self-Assessment and Faculty Assessment of Performance in an
      Interprofessional Error Disclosure Simulation Training Program.
AB  - Objectives. To conduct a prospective evaluation for effectiveness of an error
      disclosure assessment tool and video recordings to enhance student learning and
      metacognitive skills while assessing the IPEC competencies. Design. The
      instruments for assessing performance (planning, communication, process, and team
      dynamics) in interprofessional error disclosure were developed. Student self
      assessment of performance before and after viewing the recordings of their
      encounters were obtained. Faculty used a similar instrument to conduct real-time
      assessments. An instrument to assess achievement of the Interprofessional
      Education Collaborative (IPEC) core competencies was developed. Qualitative data
      was reviewed to determine student and faculty perceptions of the simulation.
      Assessment. The interprofessional simulation training involved a total of 233
      students (50 dental, 109 nursing and 74 pharmacy). Use of video recordings made a
      significant difference in student self-assessment for communication and process
      categories of error disclosure. No differences in student self-assessments were
      noted among the different professions. There were differences among the family
      member affects for planning and communication for both pre-video and post-video
      data. There were significant differences between student self-assessment and
      faculty assessment for all paired comparisons, except communication in student
      post-video self-assessment. Students' perceptions of achievement of the IPEC core
      competencies were positive. Conclusion. The use of assessment instruments and
      video recordings may have enhanced students' metacognitive skills for assessing
      performance in interprofessional error disclosure. The simulation training was
      effective in enhancing perceptions on achievement of IPEC core competencies. This
      enhanced assessment process appeared to enhance learning about the skills needed
      for interprofessional error disclosure.

PMID- 28496275
TI  - Qualitative Analysis of Student Perceptions Comparing Team-based Learning and
      Traditional Lecture in a Pharmacotherapeutics Course.
AB  - Objective. To qualitatively compare students' attitudes and perceptions regarding
      team-based learning (TBL) and lecture. Design. Students were exposed to TBL and
      lecture in an elective pharmacotherapeutics course in a randomized, prospective,
      cross-over design. After completing the course, students provided their attitudes
      and perceptions through a written self-reflection and narrative questions on the
      end-of-course evaluation. Student responses were reviewed using a grounded theory
      coding method. Assessment. Students' responses yielded five major themes: impact
      of TBL on learning, perceptions about TBL learning methods, changes in approaches
      to learning, building skills for professional practice, and enduring challenges.
      Overall, students report TBL enhances their learning of course content (knowledge
      and application), teamwork skills, and lifelong learning skills. Conclusion.
      Students' attitudes and perceptions support TBL as a viable pedagogy for teaching
      pharmacotherapeutics.

PMID- 28496276
TI  - Using Patient Case Video Vignettes to Improve Students' Understanding of Cross
      cultural Communication.
AB  - Objective. To develop, implement, and assess whether simulated patient case
      videos improve students' understanding of and attitudes toward cross-cultural
      communication in health care. Design. Third-year pharmacy students (N=159) in a
      health care communications course participated in a one-hour lecture and two-hour
      workshop on the topic of cross-cultural communication. Three simulated pharmacist
      patient case vignettes highlighting cross-cultural communication barriers, the
      role of active listening, appropriate use of medical interpreters, and useful
      models to overcome communication barriers were viewed and discussed in groups of
      20 students during the workshop. Assessment. A pre-lecture and post-workshop
      assessed the effect on students' understanding of and attitudes toward cross
      cultural communication. Understanding of cross-cultural communication concepts
      increased significantly, as did comfort level with providing cross-cultural care.
      Conclusion. Use of simulated patient case videos in conjunction with an
      interactive workshop improved pharmacy students' understanding of and comfort
      level with cross-cultural communication skills and can be useful tools for
      cultural competency training in the curriculum.

PMID- 28496277
TI  - A Framework for Integrating Biosimilars Into the Didactic Core Requirements of a
      Doctor of Pharmacy Curriculum.
AB  - Biologic drugs approved via the abbreviated United States biosimilar approval
      pathway are anticipated to improve access to medications by addressing increasing
      health care expenditures. Surveys of health care practitioners indicate that
      there is inadequate knowledge and understanding about biosimilars; this must be
      addressed to ensure safe and effective use of this new category of products.
      Concepts of biosimilar development, manufacturing, regulation, naming, formulary,
      and inventory considerations, as well as patient and provider education should be
      included within the doctor of pharmacy (PharmD) curriculum as preparation for
      clinical practice. Based on these considerations, we propose that PharmD
      graduates be required to have knowledge in the following domains regarding
      biologics and biosimilars: legal definition, development and regulation, state
      pharmacy practice laws, and pharmacy practice management. We link these general
      biosimilar concepts to the Accreditation Council for Pharmacy Education (ACPE)
      Standards 2016 and Center for the Advancement of Pharmacy Education (CAPE)
      Outcomes 2013, and provide example classroom learning objectives, in-class
      activities, and assessments to guide implementation.

PMID- 28496278
TI  - Point/Counterpoint: Are Outstanding Leaders Born or Made?
AB  - The question of whether outstanding leaders are born or made has been debated for
      years. There are numerous examples of historical figures that came naturally to
      leadership, while others developed their leadership skills through tenacity and
      experience. To understand leadership, both nature (the genetic component) and
      nurture (the environmental influences) must be considered. This article
      represents the work of two Academic Leadership Fellows Program groups who debated
      each position at the 2016 American Association of Colleges of Pharmacy (AACP)
      Interim Meeting in Tampa, Fla., in February 2016.

PMID- 28496279
TI  - Professional Attire Dress Codes for PharmD Programs Should Not Be Mandatory.

PMID- 28496280
TI  - Expanding Dress Code Requirements in the Doctor of Pharmacy Program.

PMID- 28496281
TI  - Comparison of Herbarium Label Data and Published Medicinal Use: Herbaria as an
      Underutilized Source of Ethnobotanical Information.
AB  - The use of herbarium specimens as vouchers to support ethnobotanical surveys is
      well established. However, herbaria may be underutilized resources for
      ethnobotanical research that depends on the analysis of large datasets compiled
      across multiple sites. Here, we compare two medicinal use datasets, one sourced
      from published papers and the other from online herbaria to determine whether
      herbarium and published data are comparable and to what extent herbarium
      specimens add new data and fill gaps in our knowledge of geographical extent of
      plant use. Using Brazilian legumes as a case study, we compiled 1400 use reports
      from 105 publications and 15 Brazilian herbaria. Of the 319 species in 107 genera
      with cited medicinal uses, 165 (51%) were recorded only in the literature and 55
      (17%) only on herbarium labels. Mode of application, plant part used, or
      therapeutic use was less often documented by herbarium specimen labels (17% with
      information) than publications (70%). However, medicinal use of 21 of the 128
      species known from only one report in the literature was substantiated from
      independently collected herbarium specimens, and 58 new therapeutic applications,
      25 new plant parts, and 16 new modes of application were added for species known
      from the literature. Thus, when literature reports are few or information-poor,
      herbarium data can both validate and augment these reports. Herbarium data can
      also provide insights into the history and geographical extent of use that are
      not captured in publications.

PMID- 28496282
TI  - A comparison of race-related pain stereotypes held by White and Black
      individuals.
AB  - Pain judgments are the basis for pain management. The purpose of this study was
      to assess Black and White participants' race-related pain stereotypes.
      Undergraduates (n=551) rated the pain sensitivity and willingness to report pain
      for the typical Black person, White person, and themselves. Participants,
      regardless of race, rated the typical White person as being more pain sensitive
      and more willing to report pain than the typical Black person. White participants
      rated themselves as less sensitive and less willing to report pain than same-race
      peers; however, Black participants rated themselves as more pain sensitive and
      more willing to report pain than same-race peers. These findings highlight
      similarities and differences in racial stereotypic pain beliefs held by Black and
      White individuals.

PMID- 28496283
TI  - The 9/11 Dust Cloud and Pregnancy Outcomes: A Reconsideration.
AB  - The events of 9/11 released a million tons of toxic dust into lower Manhattan, an
      unparalleled environmental disaster. It is puzzling then that the literature has
      shown little effect of fetal exposure to the dust. However, inference is
      complicated by pre-existing differences between the affected mothers and other
      NYC mothers as well as heterogeneity in effects on boys and girls. Using all
      births in utero on 9/11 in NYC and comparing them to their siblings, we show that
      residence in the affected area increased prematurity and low birth weight,
      especially for boys.

PMID- 28496284
TI  - Using Hydrazine to Link Ferrocene with Re(CO)3: A Modular Approach.
AB  - Acetyl ferrocene and diacetyl ferrocene both readily react with an excess of
      hydrazine to afford the corresponding hydrazone compounds. These compounds can
      then be linked to Re(CO)3 via a metal-mediated Schiff base reaction, resulting in
      a series of ferrocene-Re(CO)3 conjugates with different stoichiometries.
      Conjugates with 1:1, 1:2, and 2:1 ferrocene: Re(CO)3 ratios can be produced via
      this "modular" type synthesis approach. Several examples of these conjugates were
      structurally characterized, and their spectroscopic, electrochemical, and
      spectroelectrochemical behaviors were investigated. The electronic structures of
      these compounds were also probed using DFT and TDDFT calculations.

PMID- 28496285
TI  - Partial identification in the statistical matching problem.
AB  - The statistical matching problem involves the integration of multiple datasets
      where some variables are not observed jointly. This missing data pattern leaves
      most statistical models unidentifiable. Statistical inference is still possible
      when operating under the framework of partially identified models, where the goal
      is to bound the parameters rather than to estimate them precisely. In many
      matching problems, developing feasible bounds on the parameters is equivalent to
      finding the set of positive-definite completions of a partially specified
      covariance matrix. Existing methods for characterising the set of possible
      completions do not extend to high-dimensional problems. A Gibbs sampler to draw
      from the set of possible completions is proposed. The variation in the observed
      samples gives an estimate of the feasible region of the parameters. The Gibbs
      sampler extends easily to high-dimensional statistical matching problems.

PMID- 28496286
TI  - Mental Health Interventions for Children in Foster Care: A Systematic Review.
AB  - Children in foster care have high rates of adverse childhood experiences and are
      at risk for mental health problems. These problems can be difficult to
      ameliorate, creating a need for rigorous intervention research. Previous research
      suggests that intervening with children in foster care can be challenging for
      several reasons, including the severity and complexity of their mental health
      problems, and challenges engaging this often transitory population in mental
      health services. The goal of this article was to systematically review the
      intervention research that has been conducted with children in foster care, and
      to identify future research directions. This review was conducted on mental
      health interventions for children, ages 0 to 12, in foster care, using ERIC,
      CINAHL, PsycINFO, PubMed, ProQuest's Dissertation and Theses Database, Social
      Services Abstracts, and Social Work Abstracts. It was restricted to interventions
      that are at least "possibly efficacious" (i.e., supported by evidence from at
      least one randomized controlled trial). Studies were evaluated for risk of bias.
      Ten interventions were identified, with diverse outcomes, including mental health
      and physiological. Six interventions were developed for children in foster care.
      Interventions not developed for children in foster care were typically adapted to
      the foster context. Most interventions have yet to be rigorously evaluated in
      community-based settings with children in foster care. Little research has been
      conducted on child and family engagement within these interventions, and there is
      a need for more research on moderators of intervention outcomes and subgroups
      that benefit most from these interventions. In addition, there is not consensus
      regarding how to adapt interventions to this population. Future research should
      focus on developing and testing more interventions with this population,
      rigorously evaluating their effectiveness in community-based settings,
      determining necessary adaptations, and identifying which interventions work best
      for whom.

PMID- 28496287
TI  - A systems theoretic approach to analysis and control of mammalian circadian
      dynamics.
AB  - The mammalian circadian clock is a complex multi-scale, multivariable biological
      control system. In the past two decades, methods from systems engineering have
      led to numerous insights into the architecture and functionality of this system.
      In this review, we examine the mammalian circadian system through a process
      systems lens. We present a mathematical framework for examining the cellular
      circadian oscillator, and show recent extensions for understanding population
      scale dynamics. We provide an overview of the routes by which the circadian
      system can be systemically manipulated, and present in silico proof of concept
      results for phase resetting of the clock via model predictive control.

PMID- 28496288
TI  - Mesopredator behavioral response to olfactory signals of an apex predator.
AB  - Olfactory signals constitute an important mechanism in interspecific
      interactions, but little is known regarding their role in communication between
      predator species. We analyzed the behavioral responses of a mesopredator, the red
      fox (Vulpes vulpes), to an olfactory cue (scat) of an apex predator, the lynx
      (Lynx lynx) in Bialowieza Primeval Forest, Poland, using video camera traps. Red
      fox visited sites with scats more often than expected and the duration of their
      visits was longer at scat sites than at control sites (no scat added). Vigilant
      behavior, sniffing and scent marking (including over-marking) occurred more often
      at scat sites compared to control sites, where foxes mainly passed by. Vigilance
      was most pronounced during the first days of the recordings. Red fox behavior was
      also influenced by foxes previously visiting scat sites. They sniffed and scent
      marked (multiple over-marking) more frequently when the lynx scat had been over
      marked previously by red fox. Fox visits to lynx scats may be seen as a trade-off
      between obtaining information on a potential food source (prey killed by lynx)
      and the potential risk of predation by an apex predator.

PMID- 28496289
TI  - What if Reading is Easy but Unimportant? How Students' Patterns of Affirming and
      Undermining Motivation for Reading Information Texts Predict Different Reading
      Outcomes.
AB  - Many affirming and undermining motivational constructs affect students as they
      read information texts, but few researchers have explored how these motivations
      are patterned within students. In this study we used cluster analysis to classify
      middle school students (n = 1,134) based on their patterns of self-efficacy,
      perceived difficulty, value, and devalue for reading school information texts. We
      then compared how the patterns predicted students' language arts grades, science
      information text comprehension, and dedication to reading school information
      texts. We found and validated a four-cluster solution. One cluster included a
      pattern of high affirming and low undermining motivations, and another included
      low affirming and high undermining motivations. Students with these patterns
      earned the highest and lowest scores, respectively, on all outcomes. A third
      pattern showed high self-efficacy/low difficulty with low value/high devalue, and
      a fourth showed moderate levels of all four motivational constructs. Students
      with the high efficacy and devalue pattern showed high information text
      comprehension but relatively low dedication. Students with the moderate pattern
      showed high dedication but low initial information text comprehension. Students
      with these two patterns earned similar grades. We discuss the implications of our
      findings for motivation theories and for school instruction that involves
      information text reading.

PMID- 28496290
TI  - Quantitative analysis of amphiphilic N-alkyloxypyridinecarboximidamide by liquid
      chromatography-tandem mass spectrometry.
AB  - LC-MS/MS method to determine hydrophobic N-alkyloxy substituted amidines: N-(2
      ethylhexyloxy)pyridine-2-carboximidamide, N-(2-ethylhexyloxy)pyridine-3
      carboximidamide, N-(2-ethylhexyloxy)pyridine-4-carboximidamide, N-decyloxy
      pyridine-2-carboximidamide, N-decyloxypyridine-3-carboximidamide and N
      decyloxypyridine-4-carboximidamide was developed and validated in terms of
      linearity, precision and accuracy. The developed method was successfully applied
      to monitor and control the synthesis process. The experimental data points
      indicated that the straight chain alkyl bromide reacted most rapidly than
      branched alkyl bromide and the enhancement of the reaction efficiency strongly
      depended on reaction temperature.

PMID- 28496291
TI  - Family Functioning and Predictors of Runaway Behavior Among At-Risk Youth.
AB  - PURPOSE: Adolescent runaway behavior is associated with a host of negative
      outcomes in young adulthood. Therefore, it is important to understand the factors
      that predict running away in youth. METHODS: Longitudinal data from 111 at-risk
      families were used to identify proximal predictors of runaway behavior over a 12
      week period. On average, youth were 14.96 years old, and 45% were female. Ten
      percent of youth ran away during the 12-week follow-up period. RESULTS: In
      bivariate analyses, running away was predicted by poorer youth- and parent-rated
      family functioning, past runaway behavior, and other problem behaviors (e.g.,
      substance use, delinquency), but not poorer perceived academic functioning.
      Results of a hierarchical logistic regression revealed a relationship between
      youth-rated family functioning and runaway behavior. However, this effect became
      non-significant after accounting for past runaway behavior and other problem
      behaviors, both of which remained significant predictors in the multivariable
      model. CONCLUSION: These findings suggest that youth who run away may be engaged
      in a more pervasive pattern of problematic behavior, and that screening and
      prevention programs need to address the cycle of adolescent defiant behavior
      associated with running away. Recommendations for clinical practice with this at
      risk population are discussed.

PMID- 28496292
TI  - Speaker verification based on the fusion of speech acoustics and inverted
      articulatory signals.
AB  - We propose a practical, feature-level and score-level fusion approach by
      combining acoustic and estimated articulatory information for both text
      independent and text dependent speaker verification. From a practical point of
      view, we study how to improve speaker verification performance by combining
      dynamic articulatory information with the conventional acoustic features. On text
      independent speaker verification, we find that concatenating articulatory
      features obtained from measured speech production data with conventional Mel
      frequency cepstral coefficients (MFCCs) improves the performance dramatically.
      However, since directly measuring articulatory data is not feasible in many real
      world applications, we also experiment with estimated articulatory features
      obtained through acoustic-to-articulatory inversion. We explore both feature
      level and score level fusion methods and find that the overall system performance
      is significantly enhanced even with estimated articulatory features. Such a
      performance boost could be due to the inter-speaker variation information
      embedded in the estimated articulatory features. Since the dynamics of
      articulation contain important information, we included inverted articulatory
      trajectories in text dependent speaker verification. We demonstrate that the
      articulatory constraints introduced by inverted articulatory features help to
      reject wrong password trials and improve the performance after score level
      fusion. We evaluate the proposed methods on the X-ray Microbeam database and the
      RSR 2015 database, respectively, for the aforementioned two tasks. Experimental
      results show that we achieve more than 15% relative equal error rate reduction
      for both speaker verification tasks.

PMID- 28496293
TI  - The Effect of Dopaminergic Medication on Joint Kinematics during Haptic Movements
      in Individuals with Parkinson's Disease.
AB  - This study examined whether altered joint angular motion during haptic
      exploration could account for a decline in haptic sensitivity in individuals with
      PD by analyzing joint position data during haptic exploration of a curved
      contour. Each participant's hand was passively moved by a robotic arm along the
      edges of a virtual box (5 cm * 15 cm) with a curved left wall. After each trial,
      participants indicated whether the contour was curved or straight. Visual,
      auditory, and tactile cues were occluded, and an electrogoniometer recorded
      shoulder and elbow joint angles during each trial. The PD group in the OFF state
      had a higher mean detection threshold (4.67 m-1) than the control group (3.06 m
      1). Individuals with PD in the OFF state also had a significantly greater
      magnitude of shoulder abduction than those in the ON state (p = 0.003) and a
      smaller magnitude of elbow flexion than those in the ON state or compared to the
      control group (both p < 0.001). These findings suggest that individuals with PD
      employ joint configurations that may contribute to haptic insensitivity. Dopamine
      replacement therapy improved joint configurations during haptic exploration in
      patients with PD, suggesting a role for dopaminergic dysfunction in PD-related
      haptic insensitivity.

PMID- 28496294
TI  - Policing 'Vancouver's Mental Health Crisis': A Critical Discourse Analysis.
AB  - In Canada and other western nations there has been an unprecedented expansion of
      criminal justice systems and a well documented increase of contact between people
      with mental illness and the police. Canadian police, especially in Vancouver,
      British Columbia, have been increasingly at the forefront of discourse and
      regulation specific to mental health. Drawing on critical discourse analysis,
      this paper to explores this claim through a case study of four Vancouver Police
      Department (VPD) policy reports on "Vancouver's mental health crisis" from 2008
      2013, which include recommendations for action. Analyzed is the VPD's role in
      framing issues of mental health in one urban space. This study is the first
      analysis to critically examine the VPD reports on mental health in Vancouver,
      B.C. The reports reproduce negative discourses about deinstitutionalization,
      mental illness and dangerousness that may contribute to further stigma and
      discrimination of persons with mental illness. Policing reports are widely drawn
      upon, thus critical analyses are particularly significant for policy makers and
      public health professionals in and outside of Canada.

PMID- 28496295
TI  - Convergence analysis of an iterative algorithm for the extended regularized
      nonconvex variational inequalities.
AB  - In this paper, we suggest and analyze a new system of extended regularized
      nonconvex variational inequalities and prove the equivalence between the
      aforesaid system and a fixed point problem. We introduce a new perturbed
      projection iterative algorithm with mixed errors to find the solution of the
      system of extended regularized nonconvex variational inequalities. Furthermore,
      under moderate assumptions, we research the convergence analysis of the suggested
      iterative algorithm.

PMID- 28496297
TI  - SemiContour: A Semi-supervised Learning Approach for Contour Detection.
AB  - Supervised contour detection methods usually require many labeled training images
      to obtain satisfactory performance. However, a large set of annotated data might
      be unavailable or extremely labor intensive. In this paper, we investigate the
      usage of semi-supervised learning (SSL) to obtain competitive detection accuracy
      with very limited training data (three labeled images). Specifically, we propose
      a semi-supervised structured ensemble learning approach for contour detection
      built on structured random forests (SRF). To allow SRF to be applicable to
      unlabeled data, we present an effective sparse representation approach to capture
      inherent structure in image patches by finding a compact and discriminative low
      dimensional subspace representation in an unsupervised manner, enabling the
      incorporation of abundant unlabeled patches with their estimated structured
      labels to help SRF perform better node splitting. We re-examine the role of
      sparsity and propose a novel and fast sparse coding algorithm to boost the
      overall learning efficiency. To the best of our knowledge, this is the first
      attempt to apply SSL for contour detection. Extensive experiments on the BSDS500
      segmentation dataset and the NYU Depth dataset demonstrate the superiority of the
      proposed method.

PMID- 28496296
TI  - A Systematic Review of the Literature on Parenting of Young Children with Visual
      Impairments and the Adaptions for Video-Feedback Intervention to Promote Positive
      Parenting (VIPP).
AB  - Secure parent-child attachment may help children to overcome the challenges of
      growing up with a visual or visual-and-intellectual impairment. A large
      literature exists that provides a blueprint for interventions that promote
      parental sensitivity and secure attachment. The Video-feedback Intervention to
      promote Positive Parenting (VIPP) is based on that blueprint. While it has been
      adapted to several specific at risk populations, children with visual impairment
      may require additional adjustments. This study aimed to identify the themes that
      should be addressed in adapting VIPP and similar interventions. A Delphi
      consultation was conducted with 13 professionals in the field of visual
      impairment to select the themes for relationship-focused intervention. These
      themes informed a systematic literature search. Interaction, intersubjectivity,
      joint attention, exploration, play and specific behavior were the themes
      mentioned in the Delphi-group. Paired with visual impairment or vision disorders,
      infants or young children (and their parents) the search yielded 74 articles,
      making the six themes for intervention adaptation more specific and concrete. The
      rich literature on six visual impairment specific themes was dominated by the
      themes interaction, intersubjectivity, and joint attention. These themes need to
      be addressed in adapting intervention programs developed for other populations,
      such as VIPP which currently focuses on higher order constructs of sensitivity
      and attachment.

PMID- 28496298
TI  - Feature-based Analysis of Large-scale Spatio-Temporal Sensor Data on Hybrid
      Architectures.
AB  - Analysis of large sensor datasets for structural and functional features has
      applications in many domains, including weather and climate modeling,
      characterization of subsurface reservoirs, and biomedicine. The vast amount of
      data obtained from state-of-the-art sensors and the computational cost of
      analysis operations create a barrier to such analyses. In this paper, we describe
      middleware system support to take advantage of large clusters of hybrid CPU-GPU
      nodes to address the data and compute-intensive requirements of feature-based
      analyses in large spatio-temporal datasets.

PMID- 28496299
TI  - Response of eyes with age-related macular degeneration to anti-VEGF drugs and
      implications for therapy planning.
AB  - PURPOSE: To evaluate the response to and dependence on aflibercept or ranibizumab
      in patients with age-related macular degeneration (AMD). METHODS: We
      retrospectively reviewed AMD patients who received induction therapy with
      aflibercept or ranibizumab for the following parameters: whether complete
      resolution of the retinal fluid ("good response") was achieved and whether
      recurrence was observed within 3 months ("dependent") after the induction
      treatment. With aflibercept treatment, treatment-naive eyes with a good
      response/non-dependence were recommended a pro re nata regimen, and other eyes
      were recommended a proactive bimonthly regimen, followed by monitoring of visual
      acuity (VA) for 12 months. The measured values of the groups were compared using
      one-way analysis of variance with Tukey's test to evaluate the difference between
      baseline and postinjection VA. RESULTS: Among the treatment-naive eyes, 76% had a
      good response to aflibercept and 37% of these were aflibercept-dependent, while
      58% had a good response to ranibizumab but 51% of these were ranibizumab
      dependent. Among the eyes that converted from ranibizumab treatment, 92% of the
      good responders to ranibizumab with dependence and 76% of the poor responders on
      ranibizumab had a good response to aflibercept. With aflibercept treatment, the
      mean VA of treatment-naive patients was significantly better than the baseline VA
      over 12 months (P<0.001), and the VA of the converted group improved
      significantly with proactive treatment and the improvement was continuously
      maintained from 6 to 12 months. CONCLUSION: The evaluation of response to and
      dependence on anti-vascular endothelial growth factor therapies in AMD was useful
      and practical in managing therapeutic protocols to obtain a good VA.

PMID- 28496300
TI  - Prospective evaluation of intense pulsed light and meibomian gland expression
      efficacy on relieving signs and symptoms of dry eye disease due to meibomian
      gland dysfunction.
AB  - PURPOSE: The aim of this study was to estimate the efficacy of intense pulsed
      light (IPL), followed by meibomian gland expression (MGX), for reducing the
      number and severity of signs and symptoms of dry eye disease (DED) secondary to
      meibomian gland dysfunction (MGD). PATIENTS AND METHODS: In a prospective study
      conducted in two sites, 40 subjects (80 eyes) with moderate to severe MGD were
      enrolled. Major inclusion criteria consisted of at least two of the following
      measures being compatible with DED in both eyes: tear breakup time (TBUT),
      meibomian gland score (MGS), corneal fluorescein staining (CFS), Standard Patient
      Evaluation of Eye Dryness (SPEED) questionnaire, and tear film osmolarity (TFO).
      Enrolled patients underwent four treatment sessions, 3 weeks apart. Each
      treatment included the administration of 10-15 pulses of IPL on the cheeks and
      nose, followed by MGX of the upper and lower eyelids. TBUT, MGS, CFS, SPEED, TFO,
      and lipid layer thickness (LLT) were measured at baseline (BL) and at 9, 12, and
      15 weeks after BL. RESULTS: Due to different staining methods used for TBUT
      measurements, TBUT and CFS were analyzed separately for each site. From BL to the
      final follow-up, the number of signs compatible with DED decreased from 3.3+/-0.1
      to 1.4+/-0.1. TBUT improved by +93% (n=38; P<0.0001) and +425% (n=42; P<0.0001)
      for sites 1 and 2, respectively. SPEED, MGS, and CFS improved by -55% (n=80;
      P<0.0001), -36% (n=80; P<0.0001), and -58% (n=38; P<0.0001), respectively. In 20
      eyes with abnormally elevated TFO at BL, TFO improved by -7% (n=20; P<0.005). LLT
      did not change (n=38; P=0.88). CONCLUSION: In subjects with moderate to severe
      MGD, IPL combined with MGX reduced the number and severity of symptoms and signs
      of DED. Except for LLT, all examined outcome measures significantly improved
      after 15 weeks. These results support the efficacy of IPL + MGX in relieving both
      signs and symptoms of DED secondary to MGD.

PMID- 28496301
TI  - Short-term outcomes in patients with branch retinal vein occlusion who received
      intravitreal aflibercept with or without intravitreal ranibizumab.
AB  - PURPOSE: The purpose of this study was to determine the short-term outcomes for
      patients who received intravitreal aflibercept (IVA) with or without intravitreal
      ranibizumab (IVR) for macular edema (ME) due to branch retinal vein occlusion
      (BRVO). PATIENTS AND METHODS: Patients received IVA for ME due to BRVO. Patients
      who initially received IVA were defined as the treatment-naive group and those
      who were switched from IVR to IVA after ME recurrence were defined as the
      switching group. Patient outcomes were examined at 1 week and 1 month
      postinjection. RESULTS: Both groups comprised 27 eyes from 27 patients. There was
      a significant decrease in central macular thickness (CMT) at 1 week and 1 month
      postinjection in both groups. There was also a significant improvement in best
      corrected visual acuity (BCVA) at 1 week and 1 month postinjection in the
      treatment-naive group and 1 month in the switching group. Younger age was
      associated with a good BCVA at 1 month postinjection in the switching group, and
      the absence of epiretinal membrane was associated with a reduction in CMT at 1
      month postinjection in the switching group. CONCLUSION: IVA is temporarily
      effective for treating ME due to BRVO regardless of a history of IVR use.

PMID- 28496302
TI  - Goldmann tonometer error correcting prism: clinical evaluation.
AB  - PURPOSE: Clinically evaluate a modified applanating surface Goldmann tonometer
      prism designed to substantially negate errors due to patient variability in
      biomechanics. METHODS: A modified Goldmann prism with a correcting applanation
      tonometry surface (CATS) was mathematically optimized to minimize the intraocular
      pressure (IOP) measurement error due to patient variability in corneal thickness,
      stiffness, curvature, and tear film adhesion force. A comparative clinical study
      of 109 eyes measured IOP with CATS and Goldmann prisms. The IOP measurement
      differences between the CATS and Goldmann prisms were correlated to corneal
      thickness, hysteresis, and curvature. RESULTS: The CATS tonometer prism in
      correcting for Goldmann central corneal thickness (CCT) error demonstrated a
      reduction to <+/-2 mmHg in 97% of a standard CCT population. This compares to
      only 54% with CCT error <+/-2 mmHg using the Goldmann prism. Equal reductions of
      ~50% in errors due to corneal rigidity and curvature were also demonstrated.
      CONCLUSION: The results validate the CATS prism's improved accuracy and expected
      reduced sensitivity to Goldmann errors without IOP bias as predicted by
      mathematical modeling. The CATS replacement for the Goldmann prism does not
      change Goldmann measurement technique or interpretation.

PMID- 28496303
TI  - Development of a potent invigorator of immune responses endowed with both
      preventive and therapeutic properties.
AB  - This article reviews briefly the making of an immunoprophylactic-cum
      immunotherapeutic vaccine against leprosy. The vaccine is based on cultivable,
      heat-killed atypical mycobacteria, whose gene sequence is now known. It has been
      named Mycobacterium indicus pranii. It has received the approval of the Drug
      Controller General of India and the US Food and Drug Administration. Besides
      leprosy, M. indicus pranii has found utility in the treatment of category II
      ("difficult to treat") tuberculosis. It also heals ugly anogenital warts. It has
      preventive and therapeutic action against SP2/O myelomas. It is proving to be a
      potent adjuvant for enhancing antibody titers of a recombinant vaccine against
      human chorionic gonadotropin, with the potential of preventing pregnancy without
      derangement of ovulation and menstrual regularity in sexually active women.

PMID- 28496304
TI  - Evaluation of the antitumor activity of NOV202, a novel microtubule targeting and
      vascular disrupting agent.
AB  - PURPOSE: Overall, ~65% of patients diagnosed with advanced ovarian cancer (OC)
      will relapse after primary surgery and adjuvant first-line platinum- and taxane
      based chemotherapy. Significant improvements in the treatment of OC are expected
      from the development of novel compounds having combined cytotoxic and
      antiangiogenic properties that make them effective on refractory tumors. METHODS:
      Permeability of NOV202 was determined with Caco-2 monolayer assay. The compound's
      pharmacokinetic profile and plasma:brain distribution were assessed in male
      C57Bl/6 mice. The compound's impacts on tubulin, microtubules and cell cycle were
      investigated by using in vitro tubulin polymerization assay, cell-based
      immunofluorescence and live cell microscopy. The IC50 concentrations of NOV202
      were assessed in a panel of eight cancer cell lines. Impact of the compound on
      vascular tube formation was determined using the StemKit and Chick
      chorioallantoic membrane assays. The in vivo efficacy of the compound was
      analyzed with an OC xenograft mouse model. RESULTS: NOV202 was found to suppress
      cancer cell proliferation at low nanomolar concentrations (IC50 2.3-12.0 nM) and
      showed equal efficacy between OC cell line A2780 (IC50 2.4 nM) and its multidrug
      resistant subline A2780/Adr (IC50 2.3 nM). Mechanistically, NOV202 targeted
      tubulin polymerization in vitro in a dose-dependent manner and in cells induced
      an M phase arrest. In vivo, NOV202 caused a dose-dependent reduction of tumor
      mass in an A2780 xenograft model, which at the highest dose (40 mg/kg) was
      comparable to the effect of paclitaxel (24 mg/kg). Interestingly, NOV202
      exhibited vascular disrupting properties that were similar to the effects of
      Combretastatin A4. CONCLUSION: NOV202 is a novel tubulin and vascular targeting
      agent that shows strong anticancer efficacy in cells and OC xenograft models. The
      finding that the compound induced significantly more cell death in Pgp/MDR1
      overexpressing OC cells compared to vincristine and paclitaxel warrants further
      development of the compound as a new therapy for OC patients with treatment
      refractory tumors and/or relapsing disease.

PMID- 28496306
TI  - Erratum: Combined letrozole and clomiphene versus letrozole and clomiphene alone
      in infertile patients with polycystic ovary syndrome [Erratum].
AB  - [This corrects the article on p. 1427 in vol. 7.][This corrects the article on p.
      1427 in vol. 7.].

PMID- 28496305
TI  - Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric
      defense against ethanol-induced ulcer in rats.
AB  - Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as
      "Medang payung" by the Malay people, belongs to the Lauraceae family. In this
      study, methanol leaf extract of A. sesquipedalis was investigated for their acute
      toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by
      ethanol. The rats were assigned to one of five groups: normal group (group 1),
      ulcer group (group 2), control positive drug group (group 3) and two experimental
      groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract.
      The rats were sacrificed an hour after pretreatment with extracts, and their
      stomach homogenates and tissues were collected for further evaluation.
      Macroscopic and histological analyses showed that gastric ulcers in rats
      pretreated with the extract were significantly reduced to an extent that it
      allowed leukocytes penetration of the gastric walls compared with the ulcer
      group. In addition, an ulcer inhibition rate of >70% was detected in rats treated
      with both doses of A. sesquipedalis extract, showing a notable protection of
      gastric layer. Severe destruction of gastric mucosa was prevented with a high
      production of mucus and pH gastric contents in both omeprazole-treated and
      extract-treated groups. Meanwhile, an increase in glycoprotein uptake was
      observed in pretreated rats through accumulation of magenta color in Periodic
      Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats
      showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione,
      prostaglandin E2, superoxide dismutase and protein concentration levels in
      comparison with group 2. Suppression of apoptosis in gastric tissues by
      upregulation of Hsp70 protein and downregulation of Bax protein was also observed
      in rats pretreated with extract. Consistent results of a reduction of gastric
      ulcer and the protection of gastric wall were obtained for rats pretreated with
      A. sesquipedalis extract, which showed its prominent gastroprotective potential
      in rats' stomach against ethanol-induced ulcer.

PMID- 28496307
TI  - Developing selective histone deacetylases (HDACs) inhibitors through ebselen and
      analogs.
AB  - Histone deacetylases (HDACs) are key regulators of gene expression in cells and
      have been investigated as important therapeutic targets for cancer and other
      diseases. Different subtypes of HDACs appear to play disparate roles in the cells
      and are associated with specific diseases. Therefore, substantial effort has been
      made to develop subtype-selective HDAC inhibitors. In an effort to discover
      existing scaffolds with HDAC inhibitory activity, we screened a drug library
      approved by the US Food and Drug Administration and a National Institutes of
      Health Clinical Collection compound library in HDAC enzymatic assays. Ebselen, a
      clinical safe compound, was identified as a weak inhibitor of several HDACs,
      including HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9 with half
      maximal inhibitory concentrations approximately single digit of uM. Two ebselen
      analogs, ebselen oxide and ebsulfur (a diselenide analog of ebselen), also
      inhibited these HDACs, however with improved potencies on HDAC8. Benzisothiazol,
      the core structure of ebsulfur, specifically inhibited HDAC6 at a single digit of
      uM but had no inhibition on other HDACs. Further efforts on structure-activity
      relationship based on the core structure of ebsulfur led to the discovery of a
      novel class of potent and selective HDAC6 inhibitors with RBC-2008 as the lead
      compound with single-digit nM potency. This class of histone deacetylase
      inhibitor features a novel pharmacophore with an ebsulfur scaffold selectively
      targeting HDAC6. Consistent with its inhibition on HDAC6, RBC-2008 significantly
      increased the acetylation levels of alpha-tubulin in PC-3 cells. Furthermore,
      treatment with these compounds led to cell death of multiple tumor cell lines in
      a dose-dependent manner. These results demonstrated that ebselen and ebsulfur
      analogs are inhibitors of HDACs, supporting further preclinical development of
      this class of compounds for potential therapeutic applications.

PMID- 28496308
TI  - Atorvastatin, a double weapon in osteoporosis treatment: an experimental and
      clinical study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of atorvastatin on
      the bone formation and resorption markers in ovariectomized rats (experimental
      study), and to study its effect on the bone mineral density (BMD) in
      postmenopausal osteoporotic women (clinical study). MATERIALS AND METHODS: The
      study involved experimental and clinical aspects. In the experimental aspect, 42
      female Wistar rats were divided into five groups: Group I (n=6; sham-operated),
      Group II (n=6; 1 mL of carboxymethyl cellulose [CMC] was administered orally),
      Group III (n=6; 20 mg/kg orally of atorvastatin was administered), Group IV
      (n=12; untreated ovariectomized [OVX] rats and served as a model of osteoporosis
      [OP]) and Group V (n=12; 20 mg/kg orally of atorvastatin was administered to
      ovariectomized rats). After 4 weeks, serum acid phosphatase, alkaline
      phosphatase, osteocalcin, total calcium and inorganic phosphorus were assessed.
      Then, 3 um thickness lumbar and femur sections were examined using a light
      microscope to assess cortical thickness, trabecular area, numbers of osteoblasts
      and osteoclasts. In the clinical aspect, 85 post-menopausal osteoporotic females
      with recently detected hyperlipidemia participated in the study. Atorvastatin 40
      mg/day, calcium carbonate 500 mg/day and vitamin D 800 international units were
      given to all patients for a period of 18 months. BMD was measured at the start
      and at the end of the study by dual-energy X-ray absorptiometry (DEXA). RESULTS:
      In the experiment aspect, the biomarkers of bone remodeling were notably elevated
      in the OVX group. Administration of atorvastatin produced a significant decrease
      in the level of these bone metabolic markers. Atorvastatin significantly
      ameliorates osteoporotic changes induced by ovariectomy. In the clinical aspect,
      after 18 months the DEXA showed improvement in the T-score for the three measured
      zones; however, these changes were statistically significant only in the femoral
      neck area. CONCLUSION: Atorvastatin was able to decrease the rate of bone
      metabolism and increase osteogenic activity. It has dual mode of action; both
      anabolic and antiresorptive effect on bone. This lipophilic statin member may act
      as a double weapon drug.

PMID- 28496309
TI  - Effect of electromagnetic fields and antioxidants on the trace element content of
      rat teeth.
AB  - The purpose of this study was to examine the possible effect of extremely low
      frequency electromagnetic fields (ELF-EMFs), from a high-voltage source, on rat
      teeth in terms of changes in trace elements (TEs) and the effect of antioxidants
      (melatonin [MLT] and Ganoderma lucidum [GL]) in counteracting these effects. We
      used adult male Wistar albino rats with a mean weight of 250-300 g and divided
      the rats into eight groups. The groups were subjected to an ELF-EMF that was
      applied with a high-voltage line for 8 hours/day for 26 days (Groups I, II, and
      III) or 52 days (Groups V, VI, and VII). Groups IV and VIII were the 26- and 52
      day control/sham groups, respectively. Groups II and VI were treated with GL, and
      Groups III and VII were treated with MLT. MLT and GL were administered daily
      based on the weight of the animals and appropriate standards. At the end of the
      study, the rats were euthanized, and their anterior teeth were extracted. The
      teeth were preserved in pure water before evaluating the major TEs. At the end of
      the study, TE concentrations (in mg/kg) were assessed in the control and test
      groups. Compared with Group V, statistically significant differences in the
      concentrations of zinc (Zn) and strontium (Sr) were found for Group VII (ELF-EMF
      + MLT) (P<0.05). Therefore, ELF-EMF exposure can change the content of certain
      TEs in teeth and, after administering MLT and GL, the values of some of the TEs
      return to normal.

PMID- 28496310
TI  - Patient satisfaction with fixed-combination bimatoprost/timolol ophthalmic
      solution: a survey study in patients with glaucoma in China.
AB  - BACKGROUND: Poor adherence to treatment is a problem in glaucoma, and patient
      dissatisfaction with topical glaucoma medication is a barrier to adherence. The
      objective of this study was to evaluate glaucoma patients' satisfaction with
      fixed-combination bimatoprost/timolol ophthalmic solution (BTFC). METHODS: This
      observational, multicenter study was conducted in China in adults with glaucoma
      treated with BTFC for 1-3 months. Five hundred patients answered a questionnaire
      concerning their demographic characteristics, history of glaucoma and topical
      glaucoma treatment, and use of BTFC. The primary endpoint was patient
      satisfaction with BTFC assessed on a 10-point scale (1= very dissatisfied, 10=
      very satisfied). RESULTS: Patients received BTFC alone (65%) or with other
      treatments (35%), most commonly a carbonic anhydrase inhibitor. Most patients
      (87%) used BTFC as a replacement for other medication, usually a beta-blocker or
      prostaglandin analog; 13% received BTFC as add-on treatment. Key reasons for
      initiating BTFC therapy were poor efficacy of previous treatment (72% of
      patients) and side effects of previous treatment (32% of patients). Most patients
      agreed or very much agreed that BTFC provided better control of intraocular
      pressure (85% of patients), had a simpler administration (87% of patients), and
      was associated with better tolerance and comfort (82% of patients) compared with
      their previous treatment. Mean satisfaction scores were significantly higher for
      BTFC than for previous treatments among all patients (7.8 versus 6.0; P<0.0001)
      and within patient subgroups based on demographic characteristics, pattern of
      BTFC use, and previous treatment. CONCLUSION: Patients were highly satisfied with
      BTFC used alone or concomitantly with another topical medication. Patients
      previously treated with a beta-blocker, prostaglandin analog, carbonic anhydrase
      inhibitor, alpha-adrenergic agonist, or combination of two medications were more
      satisfied with BTFC than with their previous treatment. Most reported that
      intraocular pressure control, tolerability, and ease of administration improved
      with BTFC.

PMID- 28496311
TI  - Letter regarding the article "The impact of hypomagnesemia on erectile
      dysfunction in elderly, non-diabetic, stage 3 and 4 chronic kidney disease
      patients: a prospective cross-sectional study".

PMID- 28496312
TI  - Body mass index is associated with type 2 diabetes mellitus in Chinese elderly.
AB  - BACKGROUND: There is limited information on the association between metabolic
      syndrome components including body mass index (BMI) and type 2 diabetes mellitus
      in elderly Chinese population. Therefore, we investigated whether components of
      metabolic syndrome are associated with type 2 diabetes mellitus in elderly.
      METHODS: A total of 479 hospitalized patients (aged 65-95 years) with recently
      diagnosed type 2 diabetes mellitus were studied retrospectively in a cross
      sectional study and compared with 183 subjects with prediabetes and 62 subjects
      without glucose metabolism abnormalities. RESULTS: BMI (24.69+/-3.59 versus
      23.92+/-3.08 and 23.56+/-3.25 kg/m2), blood pressure, cholesterol, triglyceride,
      liver enzymes and prevalence of fatty liver were higher in patients with type 2
      diabetes mellitus as compared with elderly subjects with prediabetes or normal
      glucose metabolism separately (all P<0.05). Multivariable regression analysis
      showed that BMI was associated positively with insulin resistance and inversely
      with insulin sensitivity in type 2 diabetes mellitus group (all P<0.05).
      CONCLUSION: Higher BMI was associated with increased insulin resistance and
      decreased insulin sensitivity in elderly Asian population with type 2 diabetes
      mellitus.

PMID- 28496313
TI  - Relationships of pancreatic beta-cell function with microalbuminuria and
      glomerular filtration rate in middle-aged and elderly population without type 2
      diabetes mellitus: a Chinese community-based analysis.
AB  - BACKGROUND: Relationships of pancreatic beta-cell function abnormality with
      microalbuminuria (MA) and glomerular filtration rate (GFR) may differ by age,
      ethnicity and accompanied diseases. Previous studies were generally conducted in
      Western adult patients with type 2 diabetes mellitus (T2DM), and it is uncertain
      whether pancreatic beta-cell function is associated with MA and GFR in Chinese
      community-dwelling middle-aged and elderly population without T2DM. We therefore
      examined the relationships of pancreatic beta-cell function with two indices of
      renal damage, MA and GFR, in Chinese community-dwelling middle-aged and elderly
      population without T2DM. METHODS: This analysis focused on 380 Beijing residents
      older than 45 years who were free of T2DM and completed the evaluation of
      pancreatic beta-cell function. RESULTS: Median age was 67 (49-80) years. Levels
      of triglyceride, diastolic blood pressure and homeostasis model assessment-beta
      (HOMA-beta) index were positively related to urine microalbumin (P<0.05 for all).
      Age, low-density lipoprotein cholesterol levels and HOMA-beta index were
      inversely correlated with GFR, while high-density lipoprotein cholesterol levels
      were positively correlated with GFR (P<0.05 for all). In all three adjustment
      models, there was a significant positive association between HOMA-beta index and
      MA; subjects with higher beta-cell function had higher odds of MA (P<0.05 for
      all). There was no association between HOMA-beta index and GFR <60 mL/min/1.73 m2
      in any model (P>0.05 for all). CONCLUSION: Modeling the pancreatic beta-cell
      function with different adjusted variables provided the same conclusion of
      association with MA; beta-cell function was positively associated with MA.
      Additionally, there was a specific difference in the adjusted associations of
      pancreatic beta-cell function with MA and GFR <60 mL/min/1.73 m2; beta-cell
      function was not independently associated with GFR <60 mL/min/1.73 m2. This
      result indicated that abnormal pancreatic beta-cell function plays an important
      role in the development of MA.

PMID- 28496314
TI  - Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review.
AB  - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition
      predisposing individuals to chronic obstructive pulmonary disease (COPD). The
      treatment is generally extrapolated from COPD unrelated to AATD; however, most
      COPD trials exclude AATD patients; thus, this study sought to systematically
      review AATD-specific literature to assist evidence-based patient management.
      METHODS: Standard review methodology was used with meta-analysis and narrative
      synthesis (PROSPERO-CRD42015019354). Eligible studies were those of any treatment
      used in severe AATD. Randomized controlled trials (RCTs) were the primary focus;
      however, case series and uncontrolled studies were eligible. All studies had >=10
      participants receiving treatment or usual care, with baseline and follow-up data
      (>3 months). Risk of bias was assessed appropriately according to study
      methodology. RESULTS: In all, 7,296 studies were retrieved from searches; 52
      trials with 5,632 participants met the inclusion criteria, of which 26 studies
      involved alpha-1 antitrypsin augmentation and 17 concerned surgical treatments
      (largely transplantation). Studies were grouped into four management themes: COPD
      medical, COPD surgical, AATD specific, and other treatments. Computed tomography
      (CT) density, forced expiratory volume in 1 s, diffusing capacity of the lungs
      for carbon monoxide, health status, and exacerbation rates were frequently used
      as outcomes. Meta-analyses were only possible for RCTs of intravenous
      augmentation, which slowed progression of emphysema measured by CT density
      change, 0.79 g/L/year versus placebo (P=0.002), and associated with a small
      increase in exacerbations 0.29/year (P=0.02). Mortality following lung transplant
      was comparable between AATD- and non-AATD-related COPD. Surgical reduction of
      lung volume demonstrated inferior outcomes compared with non-AATD-related
      emphysema. CONCLUSION: Intravenous augmentation remains the only disease-specific
      therapy in AATD and there is evidence that this slows decline in emphysema
      determined by CT density. There is paucity of data around other treatments in
      AATD. Treatments for usual COPD may not be as efficacious in AATD, and further
      studies may be required for this disease group.

PMID- 28496315
TI  - Hydrogen coadministration slows the development of COPD-like lung disease in a
      cigarette smoke-induced rat model.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive
      pulmonary disease caused by harmful gases or particles. Recent studies have shown
      that 2% hydrogen or hydrogen water is effective in the treatment and prevention
      of a variety of diseases. This study investigated the beneficial effects and the
      possible mechanisms of different hydrogen concentrations on COPD. METHODS: A rat
      COPD model was established through smoke exposure methods, and inhalation of
      different concentrations of hydrogen was used as the intervention. The daily
      condition of rats and the weight changes were observed; lung function and right
      ventricular hypertrophy index were assessed. Also, white blood cells were
      assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue
      were analyzed using light microscopy and electron microscopy; cardiovascular
      structure and pulmonary arterial pressure changes in rats were observed using
      ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23,
      matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3,
      caspase-8 protein, and mRNA levels in the lung tissue were determined using
      immunohistochemistry, Western blot, and real-time polymerase chain reaction.
      RESULTS: The results showed that hydrogen inhalation significantly reduced the
      number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA
      and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23,
      matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue
      inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation
      ameliorated lung pathology, lung function, and cardiovascular function and
      reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6%
      hydrogen showed better outcome than inhalation of 2% hydrogen. CONCLUSION: These
      results suggest that hydrogen inhalation slows the development of COPD-like lung
      disease in a cigarette smoke-induced rat model. Higher concentrations of hydrogen
      may represent a more effective way for the rat model.

PMID- 28496316
TI  - The effect of indacaterol/glycopyrronium versus tiotropium or
      salmeterol/fluticasone on the prevention of clinically important deterioration in
      COPD.
AB  - BACKGROUND: Endpoints that evaluate deterioration rather than improvement of
      disease may have clinical utility in COPD. In this analysis, we compared the
      effects of different maintenance treatments on the prevention of clinically
      important deterioration (CID) in moderate-to-severe COPD patients. METHODS: Data
      were analyzed from three 26-week studies comparing indacaterol/glycopyrronium
      (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions
      of CID were used; each was a composite of three outcome measures typically
      associated with COPD. Definition 1 (D1) comprised a >=100 mL decrease in forced
      expiratory volume in 1 second (FEV1), a >=4-unit increase in St George's
      Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In
      Definition 2 (D2), a >=1-unit decrease in transition dyspnea index replaced FEV1.
      RESULTS: Using D1, IND/GLY significantly reduced the risk of first or sustained
      CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61,
      0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).
      With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID
      versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and
      both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72
      [0.58, 0.90], P=0.0036). CONCLUSION: These data confirm the utility of the CID
      endpoint as a means of monitoring COPD worsening in patients with moderate-to
      severe COPD. Using the CID measure, we demonstrated that dual bronchodilation
      with IND/GLY significantly reduced the risk of CID versus either long-acting
      muscarinic antagonist or long-acting beta2-agonist/inhaled corticosteroid
      treatment, providing further evidence for the benefit of dual bronchodilation in
      this patient population.

PMID- 28496318
TI  - Pri-microRNA-124 rs531564 polymorphism minor allele increases the risk of
      pulmonary artery hypertension by abnormally enhancing proliferation of pulmonary
      artery smooth muscle cells.
AB  - MicroRNA-124 (miR-124) has been reported to be downregulated in the cells exposed
      to hypoxia, which was confirmed in our study. We then used online microRNA target
      prediction tools to identify GRB2, SMAD5, and JAG1 as the candidate target genes
      of miR-124, and we next validated GRB2 as a direct gene by using luciferase
      reporter system. We also established the regulatory relationship between miR-124
      and GRB2 by showing the negative linear relationship between GRB2 and miR-124
      expression. Furthermore, we investigated the miR-124 and GRB2 expression levels
      of different genotypes including CC (n=30), GC (n=18), and GG (n=4), which
      supported the hypothesis that the presence of minor allele (C) of rs531564
      polymorphism compromised the expression of miR-124. Meanwhile, we also conducted
      real-time polymerase chain reaction and Western blot analysis to study the
      expression of GRB2 among different genotypes or pulmonary artery smooth muscle
      cells (PASMCs) treated with miR-124 mimics, GRB2 small interfering RNA, and miR
      124 inhibitors, respectively, and found that introduction of miR-124 or GRB2
      small interfering RNA could reduce the expression of GRB2 and inhibit the
      proliferation of PASMCs, while miR-124 upregulated the expression of GRB2 and
      promoted the proliferation of PASMCs. A total of 412 COPD patients with PAH
      (n=182) or without PAH (n=230) were recruited in this study, and more individuals
      carrying at least one minor allele of rs531564 were found in the COPD patients
      with PAH than in those without PAH (odds ratio: 0.61, 95% confidence interval:
      0.41-0.91; P=0.166). In conclusion, the presence of rs531564 minor allele may
      increase the risk of PAH in COPD by reducing miR-124 expression, increasing GRB2
      expression, and promoting the proliferation of PASMCs.

PMID- 28496317
TI  - Is periodontitis a comorbidity of COPD or can associations be explained by shared
      risk factors/behaviors?
AB  - COPD is recognized as having a series of comorbidities potentially related to
      common inflammatory processes. Periodontitis is one of the most common human
      inflammatory diseases and has previously been associated with COPD in numerous
      observational studies. As periodontitis and COPD are both chronic, progressive
      conditions characterized by neutrophilic inflammation with subsequent proteolytic
      destruction of connective tissue, it has been proposed that they share common
      pathophysiological processes. The mechanisms proposed to link COPD and
      periodontitis include mechanical aspiration of oral contents into the respiratory
      tree, overspill of locally produced inflammatory mediators into the systemic
      circulation or oral or lung-derived bacteremia activating an acute-phase response
      and also reactive oxygen species (ROS) and cytokine release by systemic
      neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic
      periodontitis describe altered cellular functions that would predispose to
      inflammation and tissue destruction both in the lung and in the mouth, again
      potentially connecting these conditions. However, COPD and periodontitis also
      share risk factors such as age, chronic tobacco smoke exposure, and social
      deprivation that are not always considered in observational and interventional
      studies. Furthermore, studies reporting associations have often utilized
      differing definitions of both COPD and periodontitis. This article reviews the
      current available evidence supporting the hypothesis that COPD and inflammatory
      periodontal disease (periodontitis) could be pathologically associated, including
      a review of shared inflammatory mechanisms. It highlights the potential
      limitations of previous studies, in particular, the lack of uniformly applied
      case definitions for both COPD and periodontitis and poor recognition of shared
      risk factors. Understanding associations between these conditions may inform why
      patients with COPD suffer such a burden of comorbid illness and new therapeutic
      strategies for both the diseases. However, further research is needed to clarify
      factors that may be directly causal as opposed to confounding relationships.

PMID- 28496319
TI  - In vivo toxicologic study of larger silica nanoparticles in mice.
AB  - Silica nanoparticles (SiNPs) are being studied and used for medical purposes. As
      nanotechnology grows rapidly, its biosafety and toxicity have frequently raised
      concerns. However, diverse results have been reported about the safety of SiNPs;
      several studies reported that smaller particles might exhibit toxic effects to
      some cell lines, and larger particles of 100 nm were reported to be genotoxic to
      the cocultured cells. Here, we investigated the in vivo toxicity of SiNPs of 150
      nm in various dosages via intravenous administration in mice. The mice were
      observed for 14 days before blood examination and histopathological assay. All
      the mice survived and behaved normally after the administration of nanoparticles.
      No significant weight change was noted. Blood examinations showed no definite
      systemic dysfunction of organ systems. Histopathological studies of vital organs
      confirmed no SiNP-related adverse effects. We concluded that 150 nm SiNPs were
      biocompatible and safe for in vivo use in mice.

PMID- 28496320
TI  - Induction of mitophagy-mediated antitumor activity with folate-appended methyl
      beta-cyclodextrin.
AB  - Mitophagy is the specific autophagic elimination system of mitochondria, which
      regulates cellular survival via the removal of damaged mitochondria. Recently, we
      revealed that folate-appended methyl-beta-cyclodextrin (FA-M-beta-CyD) provides
      selective antitumor activity in folate receptor-alpha (FR-alpha)-expressing cells
      by the induction of autophagy. In this study, to gain insight into the detailed
      mechanism of this antitumor activity, we focused on the induction of mitophagy by
      the treatment of FR-alpha-expressing tumor cells with FA-M-beta-CyD. In contrast
      to methyl-beta-cyclodextrin, FA-M-beta-CyD entered KB cells, human epithelial
      cells from a fatal cervical carcinoma (FR-alpha (+)) through FR-alpha-mediated
      endocytosis. The transmembrane potential of isolated mitochondria after treatment
      with FA-M-beta-CyD was significantly elevated. In addition, FA-M-beta-CyD lowered
      adenosine triphosphate (ATP) production and promoted reactive oxygen species
      production in KB cells (FR-alpha (+)). Importantly, FA-M-beta-CyD enhanced light
      chain 3 (LC3) conversion (LC3-I to LC3-II) in KB cells (FR-alpha (+)) and induced
      PTEN-induced putative kinase 1 (PINK1) protein expression, which is involved in
      the induction of mitophagy. Furthermore, FA-M-beta-CyD had potent antitumor
      activity in BALB/c nu/nu mice xenografted with KB cells (FR-alpha (+)) without
      any significant side effects. Taken together, these findings demonstrate that the
      autophagic cell death elicited by FA-M-beta-CyD could be associated with
      mitophagy induced by an impaired mitochondrial function.

PMID- 28496321
TI  - Development of 99mTc-radiolabeled nanosilica for targeted detection of HER2
      positive breast cancer.
AB  - The human epidermal growth factor receptor 2 (HER2) is normally associated with a
      highly aggressive and infiltrating phenotype in breast cancer lesions with
      propensity to spread into metastases. In clinic, the detection of HER2 in primary
      tumors and in their metastases is currently based on invasive methods. Recently,
      nuclear molecular imaging techniques, including positron emission tomography and
      single photon emission computed tomography (SPECT), allowed the detection of HER2
      lesions in vivo. We have developed a 99mTc-radiolabeled nanosilica system,
      functionalized with a trastuzumab half-chain, able to act as drug carrier and
      SPECT radiotracer for the identification of HER2-positive breast cancer cells. To
      this aim, nanoparticles functionalized or not with trastuzumab half-chain, were
      radiolabeled using the 99mTc-tricarbonyl approach and evaluated in HER2 positive
      and negative breast cancer models. Cell uptake experiments, combined with flow
      cytometry and fluorescence imaging, suggested that active targeting provides
      higher efficiency and selectivity in tumor detection compared to passive
      diffusion, indicating that our radiolabeling strategy did not affect the
      nanoconjugate binding efficiency. Ex vivo biodistribution of 99mTc-nanosilica in
      a SK-BR-3 (HER2+) tumor xenograft at 4 h postinjection was higher in targeted
      compared to nontargeted nanosilica, confirming the in vitro data. In addition,
      viability and toxicity tests provided evidence on nanoparticle safety in cell
      cultures. Our results encourage further assessment of silica 99mTc-nanoconjugates
      to validate a safe and versatile nanoreporter system for both diagnosis and
      treatment of aggressive breast cancer.

PMID- 28496322
TI  - Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its
      central analgesic effects under red light.
AB  - Cobra neurotoxin (CNT), a peptide isolated from snake venom of Naja naja atra,
      shows central analgesic effects in our previous research. In order to help CNT
      pass through blood-brain barrier (BBB) and improve its central analgesic effects,
      a new kind of CNT nanocapsules were prepared by double emulsification with
      soybean lecithin and cholesterol as the shell, and pheophorbide as the
      photosensitizer added to make it photoresponsive. The analgesic effects were
      evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT
      nanocapsules had an average particle size of 229.55 nm, zeta potential of -53.00
      mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the
      pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly
      distributed in outer layer of the CNT nanocapsules and increased the release of
      the CNT nanocapsules after 650 nm illumination. The central analgesic effects
      were improved after intraperitoneal injection of CNT at 25 and 50 ug.kg-1 under
      650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by
      red light generated reactive oxygen species which opened the nanocapsules and BBB
      and helped the CNT enter the brain. This research provides a new drug delivery
      for treatment of central pain.

PMID- 28496323
TI  - A novel nanoemulsion-based method to produce ultrasmall, water-dispersible
      nanoparticles from chitosan, surface modified with cell-penetrating peptide for
      oral delivery of proteins and peptides.
AB  - A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making
      ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from
      chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O
      nanoemulsion serve as "nano-containers and nano-reactors". The entrapped polymer
      chains of CS inside these "nano-reactors" are covalently cross-linked with the
      chains of polyethylene glycol (PEG), leading to rigidification and formation of
      NPs. These NPs possess excessive swelling properties in aqueous medium and
      preserve integrity in all pH ranges due to chemical cross-linking with PEG. A
      potent and newly developed cell-penetrating peptide (CPP) is further chemically
      conjugated to the surface of the NPs, leading to development of a novel peptide
      conjugated derivative of CS with profound tight-junction opening properties. The
      CPP-conjugated NPs can easily be loaded with almost all kinds of proteins,
      peptides and nucleotides for oral delivery applications. Feasibility of this
      nanoparticulate system for oral delivery of a model peptide (insulin) is
      investigated in Caco-2 cell line. The cell culture results for translocation of
      insulin across the cell monolayer are very promising (15%-19% increase), and
      animal studies are actively under progress and will be published separately.

PMID- 28496324
TI  - Preparation of zein nanoparticles by using solution-enhanced dispersion with
      supercritical CO2 and elucidation with computational fluid dynamics.
AB  - Nanoparticles have attracted more and more attention in the medicinal field. Zein
      is a biomacromolecule and can be used as a carrier for delivering active
      ingredients to prepare controlled release drugs. In this article, we presented
      the preparation of zein nanoparticles by solution-enhanced dispersion by
      supercritical CO2 (SEDS) approach. Scanning electron microscopy and transmission
      electron microscopy were applied to characterize the size and morphology of the
      obtained particles. The nozzle structure and the CO2 flow rate greatly affected
      the morphology and the size of the particles. The size of zein was able to be
      reduced to 50-350 nm according to the different conditions. The morphologies of
      the resultant zein were either sphere or the filament network consisted of
      nanoparticles. The influence of the nozzle structure and the CO2 flow rate on the
      velocity field was elucidated by using computational fluid dynamics. The nozzle
      structure and the CO2 flow rate greatly affected the distribution of the velocity
      field. However, a similar velocity field could also be obtained when the nozzle
      structure or the CO2 flow rate, or both were different. Therefore, the influence
      of the nozzle structure and the CO2 flow rate on the size and morphology of the
      particles, can boil down to the velocity field. The results demonstrated that the
      velocity field can be a potential criterion for producing nanoparticles with
      controllable morphology and size, which is useful to scale-up the SEDS process.

PMID- 28496325
TI  - Multifunctional and biomimetic fish collagen/bioactive glass nanofibers:
      fabrication, antibacterial activity and inducing skin regeneration in vitro and
      in vivo.
AB  - The development of skin wound dressings with excellent properties has always been
      an important challenge in the field of biomedicine. In this study, biomimetic
      electrospun fish collagen/bioactive glass (Col/BG) nanofibers were prepared.
      Their structure, tensile strength, antibacterial activity and biological effects
      on human keratinocytes, human dermal fibroblasts and human vascular endothelial
      cells were investigated. Furthermore, the Sprague Dawley rat skin defect model
      was used to validate their effect on wound healing. The results showed that
      compared with pure fish collagen nanofibers, the tensile strength of the Col/BG
      nanofibers increased to 21.87+/-0.21 Mpa, with a certain degree of antibacterial
      activity against Staphylococcus aureus. It was also found that the Col/BG
      nanofibers promoted the adhesion, proliferation and migration of human
      keratinocytes. Col/BG nanofibers induced the secretion of type one collagen and
      vascular endothelial growth factor by human dermal fibroblasts, which further
      stimulated the proliferation of human vascular endothelial cells. Animal
      experimentation indicated that the Col/BG nanofibers could accelerate rat skin
      wound healing. This study developed a type of multifunctional and biomimetic fish
      Col/BG nanofibers, which had the ability to induce skin regeneration with
      adequate tensile strength and antibacterial activity. The Col/BG nanofibers are
      also easily available and inexpensive, providing the possibility for using as a
      functional skin wound dressing.

PMID- 28496326
TI  - Gold nanoparticles attenuate metastasis by tumor vasculature normalization and
      epithelial-mesenchymal transition inhibition.
AB  - Angiogenesis is a process by which vessels are formed through preexisting ones,
      and this plays a key role in the progression of solid tumors. However, tumor
      vessels are influenced by excessive pro-angiogenic factors, resulting in deformed
      structures that facilitate the intravasation of tumor cells into the circulation
      and subsequent metastasis. Moreover, abnormal tumor vessels have low blood
      perfusion and thereby decreased oxygen infusion into tumors. This results in a
      hostile microenvironment that promotes epithelial-mesenchymal transition (EMT), a
      process in which epithelial cells lose their polarity and gain increased
      motility, which is associated with metastasis and invasion. Here, we demonstrate
      that gold nanoparticles (AuNPs) facilitate tumor vasculature normalization,
      increase blood perfusion and alleviate hypoxia in melanoma tumors. Additionally,
      AuNPs were observed to reverse EMT in tumors, accompanied by the alleviation of
      lung metastasis. These AuNPs inhibited the migration of B16F10 cells and reversed
      EMT in B16F10 cells, indicating that AuNPs could directly regulate EMT
      independent of improvements in hypoxia. Taken together, our data demonstrated
      that AuNPs could induce tumor vasculature normalization and reverse EMT,
      resulting in decreased melanoma tumor metastasis.

PMID- 28496327
TI  - Anorexia nervosa of the restrictive type and celiac disease in adolescence.
AB  - BACKGROUND: Anorexia nervosa (AN) is usually present in adolescence with symptoms
      partially overlapping celiac disease (CD), but the relationship between these two
      conditions has received little attention in the literature. The aim of this work
      was to explore this relationship, considering if CD could be associated with
      specific baseline AN-related clinical features. METHODS: In this retrospective
      study, 82 adolescent female out- and inpatients with AN of the restrictive type
      (ANr), according to the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition criteria, were recruited. CD diagnosis and related serology were
      recorded, including tissue transglutaminase type-2 antibodies, endomysial
      antibodies, and antibodies against deamidated forms of gliadin peptides. Eating
      disorder inventory-3, Children's Depression Inventory, body mass index, age, and
      disease duration data recorded at the time of blood withdrawal were also obtained
      from each patient. RESULTS: Five (6.1%) subjects presented a CD disorder
      associated with AN: none of the collected psychometric measures was significantly
      correlated with any CD-related parameter or characterized as a specific subgroup.
      CONCLUSION: CD diagnosis or serology does not relate to ANr clinical or
      demographic characteristics. However, a slight increase in prevalence with
      respect to the general population might be hypothesized and possibly elucidated
      by further studies with an appropriate design.

PMID- 28496328
TI  - Association between use of disease-modifying antirheumatic drugs and diabetes in
      patients with ankylosing spondylitis, rheumatoid arthritis, or
      psoriasis/psoriatic arthritis: a nationwide, population-based cohort study of
      84,989 patients.
AB  - PURPOSE: The aim of this study is to investigate the association between the use
      of disease-modifying antirheumatic drugs (DMARDs) and diabetes mellitus (DM) in
      patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), or
      psoriasis/psoriatic arthritis (PS/PSA). PATIENTS AND METHODS: This retrospective
      cohort study used a nationwide, population-based administrative database to
      enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti
      tumor necrosis factor (anti-TNF) drugs or nonbiologic DMARDs. Multivariable
      analysis was used to estimate the effect of different therapies on the risk of
      DM. RESULTS: The incidence rates of DM per 1,000 person-years were 8.3 for users
      of anti-TNF drugs, 13.3 for users of cyclosporine (CSA), 8.4 for users of
      hydroxychloroquine (HCQ), and 8.1 for users of other nonbiologic DMARDs. Compared
      with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios
      (aHRs) for DM were significantly lower for those who used anti-TNF drugs with HCQ
      (aHR: 0.49, 95% confidence interval [CI]: 0.36-0.66) and those who used HCQ alone
      (aHR: 0.70, 95% CI: 0.63-0.78), but not for those who used anti-TNFs without HCQ
      (aHR: 1.23, 95% CI: 0.94-1.60) or CSA (aHR: 1.14, 95% CI: 0.77-1.70). CONCLUSION:
      The aHR for DM was lowest for patients with RA and PS/PSA who initiated treatment
      with an anti-TNF agent with concomitant HCQ, followed by HCQ users. Those who
      used anti-TNF agents without HCQ and other nonbiologic DMARDs had a similar risk
      of DM.

PMID- 28496329
TI  - Minimally invasive endoscopic resection for the treatment of sinonasal
      malignancy: the outcomes and risk factors for recurrence.
AB  - PURPOSE: The role of minimally invasive endoscopic resection (MIER) in the
      treatment of sinonasal malignancy is controversial. Herein, we performed a
      retrospective review of a large case series of sinonasal malignancy patients
      treated with MIER aimed at evaluating the outcomes and identifying the risk
      factors for recurrence. METHODS: Patients with sinonasal malignancy who underwent
      MIER from March 2000 to May 2015 were enrolled, and their clinical data were
      collected. The clinical outcomes were evaluated by determining the 5-year overall
      survival (OS) and disease-free survival (DFS). The predictive factors for
      survival and potential independent risk factors for recurrence were explored.
      RESULTS: A total of 120 patients were enrolled, including 62 males and 58
      females. The mean follow-up period was 51.4 (95% confidence interval: 44.0-59.1)
      months. The most frequent histological type was mucosal malignant melanoma. The
      positive margin rate was 19.2% (23/120). Seventy-one patients had the safety
      anatomic plane (SAP). Age >=50 years, nodal metastasis, and not having the SAP
      were found to be predictive factors for survival, and absence of SAP was found to
      be an independent risk factor for recurrence. CONCLUSION: Our study indicated
      that MIER is an effective and safe surgical procedure in appropriately selected
      patients. Tumor resection with a safety anatomic boundary is likely to lead to
      improved survival and decreased recurrence. However, a larger sample and long
      term prospective observation are still required to establish the role of MIER in
      treatment of sinonasal malignancy.

PMID- 28496330
TI  - Differential cardiovascular profiles of sodium-glucose cotransporter 2
      inhibitors: critical evaluation of empagliflozin.
AB  - One of the most feared repercussions of type 2 diabetes mellitus is the risk of
      adverse cardiovascular outcomes. The current antidiabetic agents on the market
      have had difficulty in showing cardiovascular outcome improvement. The EMPA-REG
      OUTCOME trial studied the sodium-glucose cotransporter 2 inhibitor empagliflozin
      in type 2 diabetic patients at high risk of cardiovascular events. The trial
      results revealed a decrease in the composite primary end points of death from
      cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in
      those taking empagliflozin vs placebo. Those taking the medication also had a
      significant decrease in death from any cause, death from cardiovascular cause,
      and hospitalization for heart failure. The EMPA-REG trial is paradigm shifting
      because it demonstrates a clear mortality benefit to cardiovascular outcomes with
      a low side-effect profile, in contrast to prior outcome studies of hypoglycemic
      agents. Further studies are required to better clarify the long-term safety and
      efficacy of this promising class of diabetic drugs.

PMID- 28496331
TI  - Clinical and genetic characteristics in a group of 45 patients with Turner
      syndrome (monocentric study).
AB  - INTRODUCTION: Recent years have seen a shift in perspective on Turner syndrome,
      as it is no longer considered a significant disability due to therapeutic
      advances. The delay of diagnosis and the underdiagnosis are common in Turner
      syndrome, especially because of the great phenotypic variability and lack of firm
      diagnostic criteria. AIM: Our first aim was to assess the clinical and the
      cytogenetic characteristics and growth rate in growth hormone (GH)-treated
      patients as compared to those with spontaneous growth. The second aim was to
      analyze the Y chromosomal sequences. MATERIALS AND METHODS: We analyzed 45
      patients diagnosed with Turner syndrome in Genetic Pathology Centre of Cluj
      Emergency Children's Hospital. We carried out a study of the clinical features,
      the correlations between the karyotype and the phenotype, and we also made a
      research of Y chromosome sequences. RESULTS: The average age at diagnosis was
      8.9+/-5.4 years. A significant association was observed between the number of
      external phenotypical abnormalities and internal malformations (r=0.45),
      particularly the cardiovascular ones (r=0.44). Patients treated with GH showed
      improvement in growth rate, with final stature significantly better than in
      untreated patients; benefits following treatment were greater if diagnosis was
      made before the age of 5 years. Thirteen percent of patients experienced
      spontaneous and complete puberty, whereas 30% experienced incomplete puberty.
      Patients with the 45,X genotype had a greater stature deficit and a higher
      incidence of cardiac malformations, compared with patients with 45,X/46,XX mosaic
      karyotype. Y chromosome sequences were found in only one patient, who
      subsequently underwent gonadectomy. CONCLUSION: The importance of this study
      resides, to the best of our knowledge, in the fact that the largest group of
      patients in Romania was analyzed and assessed. To draw firm conclusions on the
      most valuable clinical indicators for Turner syndrome diagnosis in clinical
      practice, studies on large groups of patients should be conducted.

PMID- 28496332
TI  - Epithelial-to-mesenchymal transition correlates with gefitinib resistance in
      NSCLC cells and the liver X receptor ligand GW3965 reverses gefitinib resistance
      through inhibition of vimentin.
AB  - The role of epithelial-to-mesenchymal transition in cancer drug resistance is
      increasingly acknowledged. We examined whether epithelial-to-mesenchymal
      transition affects gefitinib resistance in non-small cell lung cancer (NSCLC)
      cells. Cell viability was detected by CCK-8 assay, VIM expression levels were
      determined by quantitative real-time polymerase chain reaction. Western blot and
      immunocytochemistry were performed to determine the protein expression level of
      vimentin. We observed morphologic differences between gefitinib-sensitive and 
      insensitive cells. Compared with the sensitive parental cell line, HCC827,
      vimentin expression levels were increased in HCC827 cells with acquired gefitinib
      resistance. Vimentin expression was also markedly upregulated in cells with
      intrinsic gefitinib resistance, and upregulated vimentin expression was
      correlated with gefitinib sensitivity. Our previous study demonstrated that
      coadministration of gefitinib and GW3965 resulted in decreased cell proliferation
      and induced apoptosis. Therefore, we investigated the relationship among GW3965,
      vimentin, and gefitinib resistance in NSCLC cells by analysis of the expression
      of vimentin in cells treated with a combination of gefitinib and GW3965.
      Gefitinib treatment led to increased levels of intracellular vimentin, while
      combined treatment with gefitinib and GW3965 resulted in decreased vimentin
      expression levels through reduction of gefitinib drug resistance in NSCLC cells.
      Overall, these findings suggest that vimentin expression is associated with
      sensitivity to gefitinib, and our study highlights the potential usefulness of
      the drug, GW3965, for reversal of gefitinib resistance through inhibition of
      vimentin expression.

PMID- 28496334
TI  - Erratum: Lead identification for the K-Ras protein: virtual screening and
      combinatorial fragment-based approaches [Corrigendum].
AB  - [This corrects the article on p. 2575 in vol. 9, PMID: 27217775.].

PMID- 28496333
TI  - Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies.
AB  - The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune
      effector cells, is credited with a protective role for normal tissue during
      immune responses, by limiting the extent of effector activation. Its presently
      known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a
      variety of cells including cancer cells, suggesting a role for these molecules as
      an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has
      recently been shown to be effective and was clinically approved in
      relapsed/refractory tumors such as malignant melanoma and lung cancer, but also
      classical Hodgkin's lymphoma. A plethora of trials exploring PD-1 blockade in
      cancer are ongoing. Here, we review the role of PD-1 signaling in lymphoid
      malignancies, and the latest results of trials investigating PD-1 or PD-L1
      blocking agents in this group of diseases. Early phase studies proved very
      promising, leading to the clinical approval of a PD-1 blocking agent in Hodgkin's
      lymphoma, and Phase III clinical studies are either planned or ongoing in most
      lymphoid malignancies.

PMID- 28496335
TI  - Knockdown of a DIS3L2 promoter upstream long noncoding RNA (AC105461.1) enhances
      colorectal cancer stem cell properties in vitro by down-regulating DIS3L2.
AB  - A large number of studies have identified plentiful long noncoding RNAs (lncRNAs)
      associated with the development of multiple cancers. Some lncRNAs have also been
      found to be strongly linked with stem cell properties such as pluripotency and
      differentiation. However, only in a few cases have cancer stem cell (CSC)-related
      lncRNAs been studied. Commonly, the expression and function of lncRNAs are
      associated with adjacent protein coding transcripts. In the present study, we
      found an lncRNA (AC105461.1), a promoter upstream transcript of DIS3 mitotic
      control homolog (Saccharomyces cerevisiae)-like 2 (DIS3L2), may be closely
      connected with "stem cell-like" properties. We firstly investigated whether the
      expression of AC105461.1 was down-regulated in colorectal cancer (CRC) tissue
      samples. Subsequently, we explored the expression pattern of the lncRNA/mRNA gene
      pair between AC105461.1 and DIS3L2 in 47 CRC specimens by real-time polymerase
      chain reaction. The results showed that the expression of AC105461.1 was
      positively correlated with that of DIS3L2. Through CRC cell lines screening
      experiment, we found that AC105461.1 expression was highest in SW480 and lowest
      in SW620 cells. Moreover, the results obtained by overexpression experiment
      indicated that AC105461.1 expression was markedly elevated and DIS3L2 expression
      level was also apparently upregulated by plasmid cDNA-AC105461.1. In contrast, we
      further found that AC105461.1 expression level in AC105461.1 siRNA group was
      significantly knocked down in SW480 cells. Meanwhile, DIS3L2 expression was also
      markedly decreased. Importantly, we noticed that AC105461.1 overexpression
      impaired CSC properties, while its knockdown enhanced CSC properties, including
      self-renewal, migration, and invasion abilities. To further identify the
      influence of AC105461.1 expression on CSCs properties in CRC, CD133 and CD44, as
      current universal markers for characterizing CRC stem cells, were selected to
      perform flow cytometry analysis. As a result, we found that AC105461.1
      overexpression reduced the percentage of CD133+CD44+, whereas its knockdown
      increased the percentage of CD133+CD44+. Taken together, our findings indicated
      that AC105461.1 may be a regulator of DIS3L2 and a mediator of CRC stem cells,
      and we speculate that AC105461.1 could be regarded as a promising biomarker and
      therapeutic target for CRC.

PMID- 28496336
TI  - Curcumin exerts its antitumor activity through regulation of miR-7/Skp2/p21 in
      nasopharyngeal carcinoma cells.
AB  - Curcumin, a natural polyphenol compound, exhibits tumor suppressive activity in a
      wide spectrum of cancers, including nasopharyngeal carcinoma cells. However, the
      exact molecular mechanisms governing this tumor suppressive activity remain
      elusive. Multiple studies have revealed that miRNAs are critically involved in
      tumorigenesis, indicating that targeting miRNAs could be a therapeutic strategy
      for treating human cancer. In the current study, we set out to determine whether
      curcumin regulates miR-7 expression in nasopharyngeal carcinoma cells. We found
      that curcumin inhibited cell growth, induced apoptosis, retarded cell migration
      and invasion, and triggered cell cycle arrest in the human nasopharyngeal
      carcinoma cell lines CNE1 and CNE2. Importantly, we observed that curcumin
      upregulated the expression of miR-7 and subsequently inhibited Skp2, a direct miR
      7 target. Our results identified that upregulation of miR-7 by curcumin could
      benefit nasopharyngeal carcinoma patients.

PMID- 28496337
TI  - Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human
      melanoma in vitro model: studying immunogenic cell death, dendritic cell
      maturation and interaction with cytotoxic T lymphocytes.
AB  - Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer
      treatment. Oncolytic viruses with genetic modifications can further enhance the
      oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic
      vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified
      by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or
      transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared
      their properties to kill tumor cells and induce an immunogenic type of cell death
      in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on
      human immune cells, specifically regarding the activation of dendritic cells
      (DCs) and the interaction with the autologous cytotoxic T lymphocyte (CTL) clone,
      was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone
      or in combination with 5-FC and 5-FU. The influence of viral infection on cell
      viability followed a time- and multiplicity of infection dependent manner.
      Combination of virus treatment with 5-FU resulted in stronger reduction of cell
      viability. TG6002 in combination with 5-FC did not significantly strengthen the
      reduction of cell viability in this setting. Expression of calreticulin and high
      mobility group 1 protein (HMGB1), markers of immunogenic cell death (ICD), could
      be detected after viral infection. Accordingly, DC maturation was noted after
      viral oncolysis. DCs presented stronger expression of activation and maturation
      markers. The autologous CTL clone IVSB expressed the activation marker CD69, but
      viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia
      viruses JX-GFP and TG6002 lyse melanoma cells and induce additional
      immunostimulatory effects to promote antitumor immune response. Further
      investigation in vivo is needed to consolidate the data.

PMID- 28496338
TI  - The voice quality after laser surgery versus radiotherapy of T1a glottic
      carcinoma: systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: The voice quality assessment of laser surgery (LS) in
      comparison with radiotherapy (RT) remains uncertain in T1a glottic carcinoma
      treatment. This systematic review and meta-analysis were conducted to compare the
      voice quality of the two treatments. METHODS: Searches were conducted in PubMed,
      EMBASE, and Cochrane with the following index words: glotti*, layn*, vocal cord,
      vocal, surgery, cordectomy, laser, radiation, irradiation, radiotherapy, cancer,
      and carcinoma for relative studies that compared the voice quality between LS and
      RT. Random-effect models were used, and heterogeneity was assessed. RESULTS: A
      total of 14 studies were included in the analysis, consisting of 1 randomized
      controlled trial, 1 prospective study, and 12 retrospective studies. RT has
      increased the maximum phonation time (MPT; mean difference [MD] =-1.89, 95%
      confidence interval [CI] =-3.66 to -0.11, P=0.04) and decreased the fundamental
      frequency (MD =14.06, 95% CI =10.30-17.83, P<0.00001) in comparison with LS. No
      statistical difference was observed between the two groups in terms of Voice
      Handicap Index, Jitter, Shimmer, and airflow rate. CONCLUSION: RT may be a better
      choice for T1a glottic carcinoma treatment compared with LS because patients
      undergoing RT may have the advantage of increased MPT and decreased fundamental
      frequency. However, more multicenter, randomized, controlled trials are urgently
      needed to verify these differences.

PMID- 28496339
TI  - FAM172A expression in circulating tumor cells for prediction of high-risk
      subgroups of colorectal cancer [Retraction].
AB  - [This retracts the article on p. 1933 in vol. 10, PMID: 28408845.].

PMID- 28496340
TI  - Characteristics of circulating tumor cells in organ metastases, prognosis, and T
      lymphocyte mediated immune response.
AB  - Circulating tumor cells (CTCs) possess profound influence on tumor metastases and
      disease progression. This study aimed to investigate the correlation of CTCs with
      clinical characteristics and T-cell immunity, and to explore whether CTCs and the
      subpopulations can serve as an independent prognostic factor in advanced non
      small cell lung cancer (NSCLC). A prospective study was conducted in late stages
      of NSCLC patients. The levels of overall CTCs and the three subpopulation CTCs
      were enumerated using the CanPatrolTM CTC enrichment system. The information
      about the patients which included the clinical characteristics, survival status
      at the 200th day postdiagnosis, and the levels of T cells was collected. Mann
      Whitney U test, Kruskal-Wallis H test, Cox regression, and Spearman's rank
      correlation coefficient were the statistical methods used in this study. We
      detected CTCs in 27 of the 31 eligible patients; the level of epithelial
      mesenchymal circulating tumor cells (EMCTCs) was higher than that of epithelial
      circulating tumor cells and that of mesenchymal circulating tumor cells (MCTCs)
      in the majority of NSCLC patients. Organ metastases were positively associated
      with the levels of overall CTCs, EMCTCs, and MCTCs (P<0.05). EMCTCs and MCTCs
      were associated with worse clinical outcomes. Additionally, the levels of EMCTCs
      were negatively associated with the levels of CD3+ T cells (P=0.01) and CD8+ T
      cells (P=0.04). In conclusion, the levels of CTCs were positively associated with
      organ metastases, particularly bone metastases, but were negatively associated
      with T-cell levels. The levels of EMCTCs and MCTCs had negative prognostic value.

PMID- 28496341
TI  - The coexpression of EphB4 and EphrinB2 is associated with poor prognosis in HER2
      positive breast cancer [Retraction].
AB  - [This retracts the article on p. 1735 in vol. 10, PMID: 28356761.].

PMID- 28496342
TI  - Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using
      cyclo-RGDfK(TPP) peptide.
AB  - BACKGROUND: Prostaspheres-based three dimensional (3D) culture models have
      provided insight into prostate cancer (PCa) biology, highlighting the importance
      of cell-cell interactions and the extracellular matrix (EMC) in the tumor
      microenvironment. Although these 3D classical spheroid platforms provide a
      significant advance over 2D models mimicking in vivo tumors, the limitations
      involve no control of assembly and structure with only limited spatial or
      glandular organization. Here, matrix-free prostaspheres from human metastatic
      prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine
      resistant (GemR) variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys
      peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo
      RGDfK(TPP)). MATERIALS AND METHODS: Microscopic imaging, immunocytochemistry
      (ICC), flow cytometry, sialidase, and WST-1 cell viability assays were used to
      evaluate the formation of multicellular tumor spheroid (MCTS), cell survival,
      morphologic changes, and expression levels of alpha2,6 and alpha2,3 sialic acid
      (SA) and E- and N-cadherin in DU145, PC3, and their GemR variants. RESULTS: By
      using the cyclo-RGDfK(TPP) peptide platform in a dose- and time-dependent manner,
      both DU145 and DU145GemR cells formed small MCTS. In contrast, PC3 and PC3GemR
      cells formed irregular multicellular aggregates at all concentrations of cyclo
      RGDfK(TPP) peptide, even after 6 days of incubation. ICC and flow cytometry
      results revealed that DU145 cells expressed higher amounts of E-cadherin but
      lower N-cadherin compared with PC3 cells. By using Maackia amurensis (alpha2,3-SA
      specific MAL-II) and Sambucus nigra (alpha2,6-SA specific SNA) lectin-based
      cytochemistry staining and flow cytometry, it was found that DU145 and DU145GemR
      cells expressed 5 times more alpha2,6-SA than alpha2,3-SA on the cell surface.
      PC3 cells expressed 4 times more alpha2,3-SA than alpha2,6-SA, and the PC3GemR
      cells showed 1.4 times higher alpha2,6-SA than alpha2,3-SA. MCTS volume was dose
      dependently reduced following pretreatment with alpha2,6-SA-specific
      neuraminidase (Vibrio cholerae). Oseltamivir phosphate enhanced cell aggregation
      and compaction of 3D MCTS formed with PC3 cells. CONCLUSION: The relative levels
      of specific sialoglycan structures on the cell surface correlate with the ability
      of PCa cells to form avascular multicellular prostaspheres.

PMID- 28496343
TI  - Gastroenterologist and nurse management of symptoms after pelvic radiotherapy for
      cancer: an economic evaluation of a clinical randomized controlled trial (the
      ORBIT study).
AB  - BACKGROUND: Over 20 distressing gastrointestinal symptoms affect many patients
      after pelvic radiotherapy, but in the United Kingdom few are referred for
      assessment. Algorithmic-based treatment delivered by either a consultant
      gastroenterologist or a clinical nurse specialist has been shown in a randomized
      trial to be statistically and clinically more effective than provision of a self
      help booklet. In this study, we assessed cost-effectiveness. METHODS: Outcomes
      were measured at baseline (pre-randomization) and 6 months. Change in quality
      adjusted life years (QALYs) was the primary outcome for the economic evaluation;
      a secondary analysis used change in the bowel subset score of the modified
      Inflammatory Bowel Disease Questionnaire (IBDQ-B). Intervention costs, British
      pounds 2013, covered visits with the gastroenterologist or nurse, investigations,
      medications and treatments. Incremental outcomes and incremental costs were
      estimated simultaneously using multivariate linear regression. Uncertainty was
      handled non-parametrically using bootstrap with replacement. RESULTS: The mean
      (SD) cost of treatment was L895 (499) for the nurse and L1101 (567) for the
      consultant. The nurse was dominated by usual care, which was cheaper and achieved
      better outcomes. The mean cost per QALY gained from the consultant, compared to
      usual care, was L250,455; comparing the consultant to the nurse, it was L25,875.
      Algorithmic care produced better outcomes compared to the booklet only, as
      reflected in the IBDQ-B results, at a cost of ~L1,000. CONCLUSION: Algorithmic
      treatment of radiation bowel injury by a consultant or a nurse results in
      significant symptom relief for patients but was not found to be cost-effective
      according to the National Institute for Health and Care Excellence (NICE)
      criteria.

PMID- 28496344
TI  - Adherence to disease-modifying therapies and its impact on relapse, health
      resource utilization, and costs among patients with multiple sclerosis.
AB  - PURPOSE: To evaluate adherence to disease-modifying therapies (DMTs) among
      patients with multiple sclerosis (MS) initiating oral and injectable DMTs, and to
      estimate the impact of adherence on relapse, health resource utilization, and
      medical costs. PATIENTS AND METHODS: Commercially insured MS patients (aged 18-65
      years, two or more MS diagnoses, one or more DMT claims) with continuous
      eligibility 12 months before and after the first DMT claim date (index date) and
      no DMT claim during the pre-index period were identified from a large commerical
      claims database for the period from January 1, 2008, to September 30, 2015.
      Adherence to the index DMT was measured by the 12-month post-index proportion of
      days covered (PDC) and compared between oral and injectable DMT initiators. After
      adjustment for sex, age at index DMT, and comorbidities, regression models
      examined the relationship between adherence and relapse risk, MS-related health
      resource utilization, and non-drug medical costs (2015 US$). RESULTS: The study
      covered 12,431 patients and nine DMTs. Adherence to the index DMT did not differ
      significantly between oral (n=1,018) and injectable (n=11,413) DMTs when assessed
      by mean PDC (0.7257+/-0.2934 vs 0.7259+/-0.2869, respectively; P=0.0787), or
      percentages achieving PDC >=0.8 (61.4% vs 58.6%, respectively; P=0.0806).
      Compared to non-adherence, adherence to DMT significantly reduced the likelihood
      of relapse in the post-index 12 months by 42%, hospitalization by 52%, and
      emergency visits by 38% (all, P<0.0001). Adherent patients would be expected to
      have on average 0.7 fewer outpatient visits annually versus non-adherent patients
      (P<0.0001). Based on the differences in predicted mean costs, adherence (vs non
      adherence) would decrease the total annual medical care costs by $5,816 per
      patient, including hospitalization costs by $1,953, emergency visits by $171, and
      outpatient visits by $2,802. CONCLUSION: Adherence remains suboptimal but
      comparable between oral and injectable DMTs. Potential health and economic
      benefits underscore the importance of improving adherence in MS.

PMID- 28496345
TI  - Glucose-lowering therapies, adequacy of metabolic control, and their relationship
      with comorbid depression in outpatients with type 2 diabetes in a tertiary
      hospital in Kenya.
AB  - BACKGROUND: Depression and diabetes mellitus are important comorbid conditions
      with serious health consequences. When depression and diabetes are comorbid,
      depression negatively affects self-management activities of diabetes with serious
      consequences. Relationship between treatment regimens of diabetes, the adequacy
      of glycemic control, and occurrence of comorbid depression is not known among our
      patients. PATIENTS AND METHODS: This was a cross-sectional descriptive study at
      the outpatient diabetes clinic of the Kenyatta National Hospital where 220
      ambulatory patients with type 2 diabetes on follow-up were systematically
      sampled. Sociodemographic data and clinical information were documented. The
      Patient Health Questionnaire-9 (PHQ-9) was used to assess depression.
      Ethylenediaminetetraacetic acid-anticoagulated blood was used for glycated
      hemoglobin (HbA1C) assay on automated system, COBAS INTEGRA machine. RESULTS: Two
      hundred twenty patients with type 2 diabetes were enrolled. The prevalence of
      comorbid depression by PHQ-9 was 32.3% (95% confidence interval: 26.4%-38.6%).
      The majority, 69.5%, had poor glycemic control, HbA1C >7.0%, mean HbA1C was
      8.9%+/-2.4%. Half, 50.4%, of the study subjects were on insulin-containing
      regimens. Over 8% (84.5%) of the participants with comorbid depression had poor
      glycemic control, which worsened with increasing severity of depression. There
      was significant correlation between comorbid depression and poor glycemic
      control, which is more consistent in the insulin-treated patients. However,
      patients on oral agents only, both with and without comorbid depression, were
      similar in their glycemic control. CONCLUSION: Among our type 2 diabetic
      population with comorbid depression, a large proportion had poor glycemic
      control, which worsened with increasing severity of depression. The insulin
      treatment increased the odds of comorbid depression and poor glycemic control in
      patients. It is justifiable to screen for comorbid depression in patients with
      type 2 diabetes who are in poor glycemic control, especially the insulin-treated,
      and then provide specific and appropriate interventions that are necessary to
      optimize their metabolic outcomes.

PMID- 28496346
TI  - Do we need to measure vitamin B12 and magnesium in morbidly obese patients with
      type 2 diabetes mellitus?
AB  - OBJECTIVE: We aimed to investigate the prevalence of B12 deficiency in metformin
      treated, morbidly obese, type 2 diabetes mellitus (T2DM) patients, compared to
      morbidly obese controls, as well as to evaluate the magnesium status. DESIGN:
      Retrospective cross-sectional analysis of plasma vitamin B12, plasma magnesium,
      glucometabolic status and clinical measurements in all consecutive morbidly obese
      patients was conducted during 1 year. SETTING: Outpatient Clinic of Obesity Care.
      SUBJECTS: One hundred forty-seven patients were evaluated: 107 morbidly obese
      controls and 40 metformin-treated, morbidly obese patients with T2DM. MAIN
      OUTCOME MEASURES: Circulating plasma concentrations of vitamin B12 (cobalamin),
      magnesium, clinical measurements and metformin medication. RESULTS: There were
      differences between the two groups regarding age, sagittal diameter, glucose
      parameters and magnesium concentrations. Longer diabetes duration was associated
      with lower magnesium. Metformin-treated T2DM patients had lower magnesium (0.76+/
      0.07 mmol/L) than controls (0.82+/-0.07 mmol/L). A subgroup analysis of 26 non
      metformin-treated T2DM patients showed a normal magnesium concentration compared
      to controls, that is, 0.81+/-0.06 mmol/L. We found no statistical difference in
      B12 concentrations between the two groups. CONCLUSION: To fully benefit from
      metformin medication, routine testing of B12 as well as magnesium in metformin
      treated, morbidly obese patients should be performed, with consideration of
      substitution to avoid low levels.

PMID- 28496347
TI  - Hearing thresholds in adult Nigerians with diabetes mellitus: a case-control
      study.
AB  - OBJECTIVES: To determine the prevalence, types and severity of hearing loss and
      associated factors in a hospital population of adult Nigerians with diabetes
      mellitus. SUBJECTS AND METHODS: This study was a prospective hospital-based study
      conducted at the Otorhinolaryngology and Diabetic Clinics of the University of
      Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu, for a period of 12 months.
      Consecutively presenting eligible adult diabetics and their age- and sex-matched
      healthy controls were recruited. Each case and control participant had clinical
      and otologic examination, followed by pure tone audiometry. Data were analyzed
      using descriptive and comparative statistics. RESULTS: There were 224 patients
      and 192 control participants. The patients comprised 112 males and 112 females
      (sex ratio=1:1), whose mean age was 47.6 years (range: 26-80 years). The
      prevalence of hearing loss was 46.9%. This comprised 43.8% sensorineural and 3.1%
      conductive hearing losses. The distribution of hearing loss by severity was mild
      25.0%, moderate 15.6% and severe 6.3%. The controls comprised 96 males and 96
      females whose mean age was 44.6 years (range: 25-79 years). The prevalence of
      hearing loss was significantly higher overall and by type (sensorineural hearing
      loss, conductive hearing loss) in cases compared with controls. CONCLUSION: The
      prevalence of hearing loss among diabetic adults at UNTH, Enugu, is comparatively
      high. Hearing loss is predominantly sensorineural and often mild to moderate in
      severity. Routine audiometric evaluation of all adult diabetics at UNTH is
      recommended.

PMID- 28496348
TI  - Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus.
AB  - The burden of diabetes mellitus (DM) in general has been extensively increasing
      over the past few years. Selective sodium glucose cotransporter-2 (SGLT2)
      inhibitors were extensively studied in type 2 DM and found to have sustained
      urinary glucose loss, improvement of glycemic control, in addition to their
      proven metabolic effects on weight, blood pressure, and cardiovascular benefits.
      Type 1 DM (T1D) patients clearly depend on insulin therapy, which till today
      fails to achieve the optimal glycemic control and metabolic targets that are
      needed to prevent risk of complications. New therapies are obviously needed as an
      adjunct to insulin therapy in order to try to achieve optimal control in T1D.
      Many oral diabetic medications have been tried in T1D patients as an adjunct to
      insulin treatment and have shown conflicting results. Adjunctive use of SGLT2
      inhibitors in addition to insulin therapies in T1D was found to have the
      potential to improve glycemic control along with decrease in the insulin doses,
      as has been shown in certain animal and short-term human studies. Furthermore,
      larger well-randomized studies are needed to better evaluate their efficacy and
      safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were
      found to be increased among users of SGLT2 inhibitors, although the incidence
      remains very low. Recent beneficial effects of ketone body production and this
      shift in fuel energetics have been suggested based on the findings of protective
      cardiovascular benefits associated with one of the SGLT2 inhibitors.

PMID- 28496349
TI  - Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis of randomized,
      placebo-controlled trials to assess the effect of vitamin K supplementation on
      insulin sensitivity. DATA SOURCES: MEDLINE, the Cochrane Library, CINAHL, Web of
      Science, Scopus, clinicaltrials.gov, and clinicaltrialresults.org were searched
      up to January 2017. Reference lists of related papers were also scanned. STUDY
      SELECTION: Randomized controlled trials were selected if they compared vitamin K
      supplementation with placebo or no treatment and reported homeostasis model
      assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin,
      C-reactive protein, adiponectin, leptin, or interleukin-6 levels. DATA
      EXTRACTION: Data extraction and study quality assessment were performed
      independently by two investigators using a standardized data extraction form. Any
      inconsistencies were resolved by a third reviewer. Effect estimates were pooled
      using inverse-variance weighted method. Heterogeneity was assessed by the I2 and
      Q statistic. RESULTS: A total of eight trials involving 1,077 participants met
      the inclusion criteria. A wide variety of participants were enrolled, including
      older men, postmenopausal women, prediabetic premenopausal women, and
      participants with a history of diabetes, hypertension, or vascular disease.
      Vitamin K1 and vitamin K2 (MK-4 and MK-7 subtypes) were assessed. Supplementation
      period ranged from 4 weeks to 3 years. Vitamin K supplementation did not affect
      insulin sensitivity as measured by homeostasis model assessment of insulin
      resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein,
      adiponectin, leptin, and interleukin-6 levels. CONCLUSION: Our analysis suggests
      no effect of vitamin K supplementation on insulin sensitivity.

PMID- 28496350
TI  - Intravenous citrulline generation test to assess intestinal function in intensive
      care unit patients.
AB  - BACKGROUND: Assessment of a quantifiable small intestinal function test is
      cumbersome. Fasting citrulline concentrations have been proposed as a measure of
      enterocyte function and elaborated into a citrulline generation test (CGT), which
      is applicable only when glutamine is administered orally. CGT is an oral test,
      limiting its use, for example, in critically ill patients. OBJECTIVE: Assessment
      of normative values and feasibility of an intravenously performed CGT in
      intensive care unit (ICU) patients with presumed gastrointestinal motility
      disturbances, especially when performed intravenously. DESIGN: CGT reference
      values were determined in 16 stable ICU patients using two different CGT methods,
      namely following either enteral or intravenous glutamine administration and both
      with simultaneous arterial and venous plasma citrulline sampling at six time
      points. Plasma amino acid analysis was performed using reverse-phase high
      performance liquid chromatography. RESULTS: The median total generation of
      citrulline in 90 min (CGT iAUCT90) was markedly higher with arterial citrulline
      sampling compared with venous citrulline sampling, being 724+/-585 and 556+/-418
      umol/L/min for enteral glutamine, respectively (p=0.02) and 977+/-283 and 769+/
      231 umol/L/min for intravenous glutamine, respectively (p=0.0004). The median
      slope (time-dependent increase) for plasma arterial and venous citrulline during
      the CGT was 0.20+/-0.16 and 0.18+/-0.12 umol/L/min for enteral glutamine,
      respectively (p=0.004) and 0.22+/-0.16 and 0.19+/-0.05 umol/L/min for intravenous
      glutamine, respectively (p=0.02). CONCLUSION: Intravenous glutamine
      administration combined with arterial plasma citrulline sampling yielded the
      least variation in CGT characteristics in stable ICU patients. A 2-point
      measurement test had comparable test characteristics as a 6-point measurement CGT
      and seems promising.

PMID- 28496351
TI  - Fatigue in patients with inflammatory bowel disease is associated with distinct
      differences in immune parameters.
AB  - BACKGROUND: Although it is well recognized that fatigue is an important problem
      in many of the quiescent inflammatory bowel disease (IBD) patients, it is unknown
      whether the immune status is different in fatigued versus non-fatigued patients.
      In this study, we contrasted various characteristics of the immune system in
      fatigued against non-fatigued patients with IBD in clinical remission. PATIENTS
      AND METHODS: Patients with IBD in clinical remission were phenotyped according to
      the Montreal classification, and the checklist individual strength-fatigue (CIS
      fatigue) was used to assess fatigue (CIS-fatigue >= 35). Flow cytometry on
      peripheral blood samples was used to investigate differences in leukocyte
      subsets. The expression of various cytokines was determined in stimulated whole
      blood and serum samples using enzyme-linked immunosorbent assay. Differences
      between fatigued and non-fatigued patients with IBD were assessed. RESULTS: In
      total, 55 patients were included in the fatigue group (FG) and 29 patients in the
      non-fatigue group (NFG). No differences in demographic and clinical
      characteristics were observed between the groups. Flow cytometry data showed a
      significantly lower percentage of monocytes (p = 0.011) and a higher percentage
      of memory T-cells (p = 0.005) and neutrophils (p = 0.033) in the FG compared with
      the NFG. Whole blood stimulation showed increased TNF-alpha (p = 0.022) and IFN
      gamma (p = 0.047) in the FG. The median serum level was significantly higher for
      IL-12 (p < 0.001) and IL-10 (p = 0.005) and lower for IL-6 (p = 0.002) in the FG
      compared with NFG. CONCLUSION: Significant differences in immune profile between
      fatigued and non-fatigued patients with IBD in clinical remission were found,
      which point out to a chronically active and Th1-skewed immune system in patients
      with fatigue. Whether these immune differences are directly involved in the
      fatigue complaints via immune-to-brain communication pathways remains to be
      determined. As such, further exploration of the underlying immune effects
      associated with fatigue is warranted to determine potential treatment options.

PMID- 28496352
TI  - Identification of expanded T-cell clones by spectratyping in nonfunctioning
      kidney transplants.
AB  - BACKGROUND: The aim of this study was the application of complementarity
      determining region-3 spectratyping analysis to determine T-cell-repertoire
      complexity and to detect T-cell-clone expansion, as a measure of immune response
      in nonfunctioning kidney transplants (group hemodialysis-transplant [HD-Tx]),
      nontransplanted dialysis patients (group hemodialysis [HD]), and normal subjects
      as controls (group C). PATIENTS AND METHODS: Analysis of T-cell receptor (TCR)
      diversity by spectratyping was applied to peripheral blood samples collected from
      21 subjects: eight in group HD-Tx, seven in group HD, and six in group C.
      RESULTS: Considering the extent of the skew in TCR variable region repertoires as
      a measure of clonal T cells, we found that the number of altered spectra showed a
      progressive increase from normal subjects to dialysis patients and to
      nonfunctioning kidney transplants, respectively. Healthy subjects had the lowest
      number of altered spectra, and patients with nonfunctioning kidney transplants
      the highest. Differences were significant for group HD-Tx vs group C (P=0.017)
      and group HD vs group C (P=0.015), but not between nonfunctioning kidney
      transplant recipients and dialysis patients (group HD-Tx vs group HD).
      CONCLUSION: Although dialysis appears to be a weaker trigger for clonal expansion
      of T cells, our data suggest that the utilization of complementarity-determining
      region-3 spectratyping analysis of the TCR repertoire might be useful to monitor
      specific immunoactivation in patients before and after kidney transplantation.

PMID- 28496353
TI  - Early manifestations of renal disease in patients with tuberous sclerosis
      complex.
AB  - OBJECTIVES: Renal manifestations are the second most significant cause of
      morbidity and mortality in patients with tuberous sclerosis complex (TSC), and
      include renal cysts, angiomyolipomas, fat-poor lesions, and malignant tumors.
      These lesions begin in childhood and often lead to chronic kidney disease (CKD).
      Little is known on the incidence of early modifiable risk factors of CKD, such as
      proteinuria and hypertension, or subtle decreases in glomerular filtration rate
      that correspond to the early stages of CKD in children with TSC. The impact of
      genotype on these early manifestations of CKD has not been investigated. DESIGN:
      Retrospective chart review of 84 children and young adults with TSC.
      MEASUREMENTS: This study assessed the prevalence of hypertension, renal
      impairment, and proteinuria, as well as the genotype-phenotype correlations.
      RESULTS: Children and young adults with TSC2 mutations had a significantly higher
      rate of renal lesions, hypertension (36% vs 14%), and decreased renal function
      than those with TSC1 mutations. CONCLUSION: On the basis of estimated glomerular
      filtration rate and blood pressure, our findings are consistent with the
      hypothesis that TSC2 mutations are associated with more severe early renal
      involvement in children. There is a compelling need for close collaboration of
      nephrologists and neurologists to provide care to pediatric patients with TSC to
      improve screening and management of early manifestations of renal disease.

PMID- 28496354
TI  - Factors associated with prescription opioid misuse in a cross-sectional cohort of
      patients with chronic non-cancer pain.
AB  - OBJECTIVE: To examine demographic features, psychosocial characteristics, pain
      specific behavioral factors, substance abuse history, sleep, and indicators of
      overall physical function as predictors of opioid misuse in patients presenting
      for new patient evaluation at a tertiary pain clinic. METHODS: Overall, 625
      patients with chronic non-cancer pain prospectively completed the Collaborative
      Health Outcomes Information Registry, assessing pain catastrophizing, National
      Institutes of Health Patient-Reported Outcomes Measurement Information System
      standardized measures (pain intensity, pain behavior, pain interference, physical
      function, sleep disturbance, sleep-related impairment, anger, depression,
      anxiety, and fatigue), and substance use history. Additional information
      regarding current opioid prescriptions and opioid misuse was examined through
      retrospective chart review. RESULTS: In all, 41 (6.6%) patients presented with
      some indication of prescription opioid misuse. In the final multivariable
      logistic regression model, those with a history of illicit drug use (odds ratio
      [OR] 5.45, 95% confidence interval [CI] 2.48-11.98, p<0.0001) and a current
      opioid prescription (OR 4.06, 95% CI 1.62-10.18, p=0.003) were at elevated risk
      for opioid misuse. Conversely, every 1-h increase in average hours of nightly
      sleep decreased the risk of opioid misuse by 20% (OR 0.80, 95% CI 0.66-0.97,
      p=0.02). CONCLUSION: These findings indicate the importance of considering
      substance use history, current opioid prescriptions, and sleep in universal
      screening of patients with chronic non-cancer pain for opioid misuse. Future work
      should target longitudinal studies to verify the causal relationships between
      these variables and subsequent opioid misuse.

PMID- 28496355
TI  - Cannabis as a substitute for prescription drugs - a cross-sectional study.
AB  - BACKGROUND: The use of medical cannabis is increasing, most commonly for pain,
      anxiety and depression. Emerging data suggest that use and abuse of prescription
      drugs may be decreasing in states where medical cannabis is legal. The aim of
      this study was to survey cannabis users to determine whether they had
      intentionally substituted cannabis for prescription drugs. METHODS: A total of
      2,774 individuals were a self-selected convenience sample who reported having
      used cannabis at least once in the previous 90 days. Subjects were surveyed via
      an online anonymous questionnaire on cannabis substitution effects. Participants
      were recruited through social media and cannabis dispensaries in Washington
      State. RESULTS: A total of 1,248 (46%) respondents reported using cannabis as a
      substitute for prescription drugs. The most common classes of drugs substituted
      were narcotics/opioids (35.8%), anxiolytics/benzodiazepines (13.6%) and
      antidepressants (12.7%). A total of 2,473 substitutions were reported or
      approximately two drug substitutions per affirmative respondent. The odds of
      reporting substituting were 4.59 (95% confidence interval [CI], 3.87-5.43)
      greater among medical cannabis users compared with non-medical users and 1.66
      (95% CI, 1.27-2.16) greater among those reporting use for managing the
      comorbidities of pain, anxiety and depression. A slightly higher percentage of
      those who reported substituting resided in states where medical cannabis was
      legal at the time of the survey (47% vs. 45%, p=0.58), but this difference was
      not statistically significant. DISCUSSION: These patient-reported outcomes
      support prior research that individuals are using cannabis as a substitute for
      prescription drugs, particularly, narcotics/opioids, and independent of whether
      they identify themselves as medical or non-medical users. This is especially true
      if they suffer from pain, anxiety and depression. Additionally, this study
      suggests that state laws allowing access to, and use of, medical cannabis may not
      be influencing individual decision-making in this area.

PMID- 28496357
TI  - Incidence and risk factors of persistent low back pain following posterior
      decompression and instrumented fusion for lumbar disk herniation.
AB  - INTRODUCTION: The aim of this study was to explore the incidence and risk factors
      of persistent low back pain (PLBP) following posterior decompression and
      instrumented fusion for lumbar disk herniation and to provide references in
      decision-making and surgical planning for both spinal surgeons and surgically
      treated patients. PATIENTS AND METHODS: By retrieving the medical records from
      January 2013 to December 2016, 221 patients were retrospectively reviewed.
      Patients were classified as having PLBP if numeric rating scale (NRS) scores were
      >50 at all postoperative follow-up time points (3 months, 6 months, and 12
      months). According to the occurrence of PLBP, patients were divided into two
      groups: PLBP group and non (N)-PLBP group. To investigate risk values for PLBP,
      the following three categorized factors were analyzed statistically. Patient
      characteristics: age, gender, body mass index (BMI), preoperative low back pain,
      comorbidity, smoking, and drinking. Surgical variables: surgical strategy,
      surgical segment, the number of fusion levels, surgery time, blood loss, and size
      of incision. Radiographic parameters: preoperative lumbar lordosis (LL),
      correction of LL at immediate postoperation, Modic changes, and preoperative
      paraspinal muscle degeneration. RESULTS: PLBP was detected in 16 patients and
      were enrolled into the PLBP group. There was no difference between the two groups
      in age, gender, BMI, comorbidity, smoking, and drinking. The preoperative low
      back pain was more severe in the PLBP group than that in the N-PLBP group. There
      was no difference in surgery time, blood loss, surgical strategy, number of
      fusion levels, and the size of incision. Surgery segment at L5-S1 was more
      prevalent in the PLBP group than that in the N-PLBP group, and there was no
      difference in preoperative LL, correction of LL, preoperative lumbar mobility,
      and Modic changes. The fatty infiltration rate (FIR) was larger in the PLBP group
      than that in the N-PLBP group. Multivariate logistic regression model revealed
      that preoperative low back pain (NRS > 35), surgery segment at L5-S1, and FIR >
      15% were independently associated with PLBP. CONCLUSION: The incidence of PLBP
      following posterior decompression and instrumented fusion for lumbar disk
      herniation is 7.2%, and the risk factors include preoperative low back pain,
      surgery segment at L5-S1, and preoperative paraspinal muscle degeneration.

PMID- 28496356
TI  - Evaluation of a specialized yoga program for persons with a spinal cord injury: a
      pilot randomized controlled trial.
AB  - OBJECTIVES: The purpose of this randomized controlled trial was to evaluate the
      effects of a specialized yoga program for individuals with a spinal cord injury
      (SCI) on pain, psychological, and mindfulness variables. MATERIALS AND METHODS:
      Participants with SCI (n=23) were outpatients or community members affiliated
      with a rehabilitation hospital. Participants were randomized to an Iyengar yoga
      (IY; n=11) group or to a 6-week wait-list control (WLC; n=12) group. The IY group
      participated in a twice-weekly 6-week seated IY program; the WLC group
      participated in the same yoga program, after the IY group's yoga program had
      ended. Pain, psychological, and mindfulness measures were collected at two time
      points for both groups (within 1-2 weeks before and after program 1 and at a
      third time point for the WLC group (within 1 week after program 2). RESULTS:
      Linear mixed-effect growth models were conducted to evaluate the main effects of
      group at T2 (postintervention), controlling for T1 (preintervention) scores. T2
      depression scores were lower (F1,18=6.1, P<0.05) and T2 self-compassion scores
      higher (F1,18=6.57, P< 0.05) in the IY group compared to the WLC group. To
      increase sample size and power, the two groups were combined and analyzed across
      time by comparing pre- and postintervention scores. Main effects of time were
      found for depression scores, (F1,14.83=6.62, P<0.05), self-compassion,
      (F1,16.6=4.49, P<0.05), mindfulness (F1,16.79=5.42, P<0.05), mindful observing
      (F1,19.82=5.06, P<0.05), and mindful nonreactivity, (F1,16.53=4.92, P<0.05), all
      showing improvement after the intervention. DISCUSSION: The results indicated
      that a specialized 6-week yoga intervention reduced depressive symptoms and
      increased self-compassion in individuals with SCI, and may also have fostered
      greater mindfulness.

PMID- 28496358
TI  - Analgesic efficacy, adverse effects, and safety of oxycodone administered as
      continuous intravenous infusion in patients after total hip arthroplasty.
AB  - BACKGROUND: Total hip arthroplasty (THA) causes extensive tissue damage and
      severe pain. This study aimed to assess the analgesic efficacy, adverse effects
      (AEs), and safety of continuous intravenous (iv) oxycodone infusion with
      ketoprofen (injected into the iv line) in patients after THA, and to assay serum
      oxycodone levels. PATIENTS AND METHODS: Fourteen patients, aged 59-82 years with
      American Society of Anesthesiologists (ASA) classification I or III, underwent
      THA with intrathecal analgesia and sedation induced by iv propofol. After the
      surgery, oxycodone (continuous iv infusion) at a dose of 1 mg/h (five patients)
      or 2 mg/h (nine patients) with 100 mg ketoprofen (injected into the iv line) was
      administered to each patient every 12 h. Pain was assessed using a numerical
      rating scale (NRS: 0 - no pain, 10 - the most severe pain) at rest and during
      movement. AEs, including hemodynamic unsteadiness, nausea, vomiting, pruritus,
      cognitive impairment, and respiratory depression, were registered during the
      first 24 h after surgery. RESULTS: Oxycodone (continuous iv infusion) at a dose
      of 2 mg/h with ketoprofen (100 mg) administered every 12 h provided satisfactory
      analgesia in all nine patients without the need of rescue analgesics within the
      first 24 h after THA. In three out of five patients, oxycodone at 1 mg/h was
      effective. Oxycodone did not induce drowsiness, vomiting, pruritus, respiratory
      depression, or changes in blood pressure. Bradycardia appeared in two patients,
      and nausea was observed in one patient. CONCLUSION: Oxycodone infusion with
      ketoprofen administered by iv is effective in patients after THA. Intravenous
      infusion of oxycodone is a predictable, stable, and safe method of drug
      administration.

PMID- 28496359
TI  - Efficacy of CR4056, a first-in-class imidazoline-2 analgesic drug, in comparison
      with naproxen in two rat models of osteoarthritis.
AB  - PURPOSE: CR4056, (2-phenyl-6-(1H-imidazol-1yl) quinazoline), an imidazoline-2
      (I2) receptor ligand, is a promising analgesic drug that has been reported to be
      effective in several animal models of pain. The aim of this study was to evaluate
      the effects of CR4056 in two well-established rat models of osteoarthritis (OA),
      mimicking the painful and structural components of human OA. METHODS: Knee OA was
      induced either by single intra-articular injection of monoiodoacetate (MIA) or by
      medial meniscal tear (MMT) in the right knee of male rats. In the MIA model,
      allodynia and hyperalgesia were measured as paw withdrawal threshold to
      mechanical stimulation. In the MMT model, pain behavior was analyzed as weight
      bearing asymmetry (i.e. difference in hind paw weight distribution, HPWD) between
      the injured and the contralateral limbs. RESULTS: Acute oral administration of
      CR4056, 14 days after MIA injection, significantly and dose-dependently reduced
      allodynia and hyperalgesia 90 minutes after treatment, whereas acute naproxen
      administration significantly reduced allodynia but not hyperalgesia. After 7 days
      of repeated treatment, both CR4056 and naproxen showed significant anti-allodynic
      and anti-hyperalgesic effects in the MIA model. Rats undergoing MMT surgery
      developed a significant and progressive asymmetry in HPWD compared with sham
      operated animals. Repeated treatment with CR4056 significantly reduced the
      progression of the pain behavior, whereas naproxen had no effects. CONCLUSION:
      The data presented here show that the I2 ligand CR4056 could be a new effective
      treatment for OA pain. The compound is currently under Phase II clinical
      evaluation for this indication.

PMID- 28496360
TI  - Epidural anesthesia for labor and delivery in a patient with May-Hegglin anomaly:
      a case report.
AB  - We report a case of May-Hegglin anomaly (MHA) in a woman who had a successful
      labor and delivery under epidural anesthesia. MHA is an inherited
      thrombocytopenia easily misdiagnosed as idiopathic (immune) thrombocytopenic
      purpura (ITP). Early and appropriate diagnosis of MHA during pregnancy is
      essential for optimal maternal and neonatal delivery outcome. Additionally, it
      can avoid unnecessary diagnostic studies, such as bone marrow aspiration and
      biopsy, and even harmful therapies with corticosteroids, immunosuppressive
      agents, and splenectomy. Consequently, the most serious impacts of this disease
      are iatrogenic managements due to misdiagnosis. It seems that in patients with
      MHA, adequate clinical coagulation is far more dependent on adequate platelet
      function than any particular platelet count. The diagnosis of MHA may pose a
      challenge for clinicians managing pregnant women with thrombocytopenia.

PMID- 28496362
TI  - Metaplastic breast carcinoma with upper limb gangrene.
AB  - Metaplastic breast carcinomas (MBCs) are rapidly growing tumors with histological
      heterogeneity, and triple negative receptor status. The aim of this case report
      is to highlight a case of advanced MBC with axillary artery infiltration leading
      to gangrene of the ipsilateral upper limb, in a young woman.

PMID- 28496361
TI  - Improved immediate breast reconstruction as a result of oncoplastic
      multidisciplinary meeting.
AB  - INTRODUCTION: The National Institute for Health and Clinical Excellence
      guidelines recommend that breast reconstruction should be available to all women
      undergoing mastectomy and discussed at the initial surgical consultation (2002,
      and updated 2009). The National Mastectomy and Breast Reconstruction Audit (2009)
      showed that 21% of mastectomy patients underwent immediate breast reconstruction
      (IBR) and 11% had delayed breast reconstruction (DBR). Breast reconstruction has
      been shown to have a positive effect on quality of life postmastectomy. This
      retrospective study investigated the impact of the introduction of a dedicated
      oncoplastic multidisciplinary meeting (OP MDM) on our unit's breast
      reconstruction rate. PATIENTS AND METHODS: A retrospective analysis of 229 women
      who underwent mastectomy, of whom 81 (35%) underwent breast reconstruction
      between April 2014 and March 2016. Data were analyzed before and after
      introduction of OP MDM in April 2015. Data on patient age, type of surgery
      (mastectomy only, mastectomy and reconstruction), timing of reconstruction (IBR,
      DBR), and type of reconstruction (implant, autologous) were collected. RESULTS:
      Between April 2015 and March 2016, following establishment of OP
      multidisciplinary team in April 2015, of the 120 patients who had mastectomy, 50
      (42%) underwent breast reconstruction with 78% (39/50) choosing IBR (56% implant
      reconstruction and 22% autologous). Compared to the period between April 2014 and
      March 2015 preceding the OP MDM, of 109 patients who underwent mastectomy, only
      31 (28%) had breast reconstruction with 64% (20/31) choosing IBR (45% implant
      reconstruction and 19% autologous). The rate of DBR was lower, 22% (11/50),
      following OP MDM compared to 35% (11/31) before OP MDM. CONCLUSION: There has
      been an increased uptake of breast reconstruction surgery from 28% to 42%. The
      biggest impact was on those opting for the immediate type reconstruction option
      (78%). The OP MDM has significantly contributed to this increased rate of
      reconstruction.

PMID- 28496363
TI  - Prognostic value of histone chaperone FACT subunits expression in breast cancer.
AB  - Understanding the underlying reasons for tumor aggressiveness, such as why some
      tumors grow slowly and locally, while others rapidly progress to a lethal
      metastatic disease, is still limited. This is especially critical in breast
      cancer (BrCa) due to its high prevalence and also due to the possibility that it
      can be detected early. Several oncogenes and tumor suppressors have been
      identified and are used in the prognosis and treatment of BrCa. However, even
      with these markers, the outcome within BrCa subtypes is highly variable.
      Chromatin organization has long been acknowledged as a factor that plays an
      important role in tumor progression, but molecular mechanisms defining chromatin
      dynamics are largely missing. We have recently found that histone chaperone FACT
      (facilitates chromatin transcription) is overexpressed in ~18-20% of BrCa cases.
      FACT is elevated upon transformation of mammary epithelial cells and is essential
      for viability of tumor cells. BrCa cells with high FACT have a more aggressive
      transcriptional program than those with low FACT cells. Based on this we propose
      that FACT may be a marker of aggressive BrCa. In this study, we aimed to
      comprehensively characterize the pattern of FACT expression in BrCa in relation
      to other molecular and clinical prognostic markers. We developed and tested an
      assay for the detection and quantitation of protein levels of both FACT subunits,
      SSRP1, and SPT16, in clinical samples. We compared the value of mRNA and protein
      as potential markers of disease aggressiveness using a large cohort of patients
      (n=1092). We demonstrated that only SSRP1 immunohistochemical staining is a
      reliable indicator of FACT levels in tumor samples. High SSRP1 correlated with
      known markers of poor prognosis, such as negative hormone receptor status,
      presence of Her2, high-grade tumors, and tumors of later clinical stage. At the
      same time, no strong correlation between SSRP1 expression and survival was
      detected when all samples were analyzed together. Clear trend toward longer
      survival of patients with low or no SSRP1 expression in tumor samples was seen in
      several subgroups of patients, and most importantly significant association of
      high SSRP1 expression with shorter disease-free survival was detected in patients
      with early-stage and low-grade BrCa, the category of patients with the highest
      demand in predictive marker of disease progression.

PMID- 28496364
TI  - Oligodendrogliomas in pediatric and adult patients: an outcome-based study from
      the Surveillance, Epidemiology, and End Result database.
AB  - INTRODUCTION: Oligodendrogliomas (OGs) account for <20% of all intracranial
      tumors and 25% of gliomas. Despite improvements in imaging techniques allowing
      for earlier diagnosis, OG is rare among the pediatric population. This study
      examines a large cohort of OG patients in an effort to define the demographic,
      clinical, and pathologic factors associated with clinical and survival outcomes.
      METHODS: Data on 7,001 OG patients were abstracted from the Surveillance,
      Epidemiology, and End Result (SEER) database (1973-2013). Pediatric patients were
      defined as <=19 years old, and adult patients were defined as age >=20 years.
      RESULTS: Among 7,001 OG patients, 6.5% were pediatric (mean age 12 +/- 6 years),
      and 93.5% were adult (mean age 46 +/- 15 years). Overall, OGs were more common
      among males, with a male-to-female ratio of 1.28:1. Overall, OGs were more common
      among Caucasians (76.9%) and also among the African American (10.8% pediatric vs.
      4.0% adult) and Hispanic (12.8% pediatric vs. 11.8% adult). OGs occurred most
      commonly in the temporal lobe of pediatric patients and the frontal lobes of
      adults. Surgical resection was the primary treatment modality for both pediatric
      and adult populations (70.6% and 40.5%), followed by combined surgery and
      radiation (19.7% and 41.2%). Surgical resection was associated with significantly
      improved survival in both groups. Pediatric patients had a lower overall
      mortality (19.8% vs. 48.5%) and lower cancer-specific mortality (17.6% vs.
      36.8%). CONCLUSION: OGs most often present in Caucasian males in their fifth
      decade of life with tumors >4 cm in size. Children typically present with tumors
      in the temporal lobe, while adults present with tumors in the frontal lobe.
      Surgical resection confers a survival advantage among all patients, especially
      pediatric patients. Overall survival (OS) and cancer-specific survival are higher
      in the pediatric population. Further studies on novel treatment techniques,
      including bevacizumab and immunotherapy approaches, are required.

PMID- 28496365
TI  - Prevalence and prognosis of stress disorders: a review of the epidemiologic
      literature.
AB  - Given the ubiquity of traumatic events, it is not surprising that posttraumatic
      stress disorder (PTSD) - a common diagnosis following one of these experiences -
      is characterized as conferring a large burden for individuals and society.
      Although there is recognition of the importance of PTSD diagnoses throughout
      psychiatry, the literature on other diagnoses one may receive following a
      stressful or traumatic event is scant. This review summarizes the literature on
      stress disorders (classified according to the International Classification of
      Diseases, 10th Edition [ICD-10]), including acute stress reaction, PTSD,
      adjustment disorder and unspecified stress reactions. This review focuses on the
      literature related to common psychiatric and somatic consequences of these
      disorders. The prevalence and incidence of each disorder are described. A review
      of epidemiologic studies on comorbid mental health conditions, including
      depression, anxiety and substance abuse, is included, as well as a review of
      epidemiologic studies on somatic outcomes, including cancer, cardiovascular
      disease and gastrointestinal disorders. Finally, the current literature on all
      cause mortality and suicide following stress disorder diagnoses is reviewed.
      Stress disorders are a critical public health issue with potentially deleterious
      outcomes that have a significant impact on those living with these disorders, the
      health care system and society. It is only through an awareness of the impact of
      stress disorders that appropriate resources can be allocated to prevention and
      treatment. Future research should expand the work done to date beyond the
      examination of PTSD, so that the field may obtain a more complete picture of the
      impact all stress disorders have on the many people living with these diagnoses.

PMID- 28496366
TI  - Factors associated with psychological distress among young women in Kisumu,
      Kenya.
AB  - BACKGROUND: Attention to mental health issues is growing globally. In many
      countries, including Kenya, however, assessment of psychological distress,
      especially in rural areas, is limited. METHODS: We analyzed data from young women
      screened for a longitudinal contraceptive ring study in Kisumu, Kenya.
      Multivariable regression analysis was used to assess factors associated with
      recent moderate and high psychological distress, as measured by the Kessler (K-6)
      psychological distress scale. RESULTS: Among the 461 women screened, most (58.4%)
      were categorized as having moderate psychological distress, 20.8% were
      categorized as having low or no psychological distress, and 20.8% were
      categorized as having high psychological distress. Moderate psychological
      distress (vs low/no) was significantly more likely among women who reported a
      history of forced sex and were concerned about recent food insecurity. High (vs
      low/no) psychological distress was significantly more likely among women who
      reported a history of forced sex, who were concerned about recent food
      insecurity, and who self-reported a sexually transmitted infection. CONCLUSION:
      To reduce psychological distress, a focus on prevention as well as care methods
      is needed. Girls need a path toward a healthy and productive adulthood with a
      focus on education, which would help them gain skills to avoid forced sex. Women
      would benefit from easy access to social services and supports that would help
      them with basic needs like food security among other things. A holistic or
      ecological approach to services that would address mental, educational, social,
      health, and economic issues may have the highest chance of having a long-term
      positive impact on public health.

PMID- 28496367
TI  - Radiation-induced vaginal stenosis: current perspectives.
AB  - Treatment of gynecological cancer commonly involves pelvic radiation therapy (RT)
      and/or brachytherapy. A commonly observed side effect of such treatment is
      radiation-induced vaginal stenosis (VS). This review analyzed the incidence,
      pathogenesis, clinical manifestation(s) and assessment and grading of radiation
      induced VS. In addition, risk factors, prevention and treatment options and
      follow-up schedules are also discussed. The limited available literature on many
      of these aspects suggests that additional studies are required to more precisely
      determine the best management strategy of this prevalent group after RT.

PMID- 28496369
TI  - Efficacy and safety of a flexible extended regimen of
      ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter,
      randomized, open-label, active-controlled study.
AB  - BACKGROUND: Dysmenorrhea is a common condition in women, which is characterized
      by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have
      been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic
      regimen of ethinylestradiol/drospirenone (28d regimen) is approved for this
      indication in Japan. AIM: The aim of this study was to assess the safety and
      efficacy of a flexible extended regimen of ethinylestradiol/drospirenone
      (flexible regimen) in Japanese women with dysmenorrhea. METHODS: This
      multicenter, open-label study was performed in Japanese women with dysmenorrhea
      who, after a baseline observational phase, were randomized to receive
      ethinylestradiol 20 MUg/drospirenone 3 mg in a flexible regimen (one tablet each
      day for 24-120 days followed by a 4-day tablet-free interval) or in the standard
      28d regimen (one tablet each day for 24 days, followed by 4 days of placebo
      tablets for six cycles). The primary endpoint was the number of days with
      dysmenorrhea of at least mild intensity over a 140-day evaluation period.
      Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were
      also assessed. RESULTS: A total of 216 women (mean age 29.7 years) were
      randomized to the flexible regimen (n=108) or 28d regimen (n=108) and 212 were
      included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107).
      Women in the flexible-regimen group reported a mean of 3.4 fewer days with
      dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in
      disease severity reported in both treatment groups. According to the
      investigators, 64.8% and 59.4% of women in the flexible-regimen and 28d-regimen
      treatment groups had "very much improved" or "much improved" disease, while 54.3%
      and 50.9% of patients reported being "very much satisfied" or "much satisfied"
      with their treatment, respectively. CONCLUSION: In Japanese women with
      dysmenorrhea, a flexible extended regimen of ethinylestradiol/drospirenone
      decreased the number of days with dysmenorrheic pain versus the traditional 28d
      regimen.

PMID- 28496370
TI  - Trends and causes of maternal mortality in Jimma University Specialized Hospital,
      southwest Ethiopia: a matched case-control study.
AB  - INTRODUCTION: Measures of maternal death are fundamental to a country's health
      and development status. In developing countries, it remains a daunting and
      largely unmet public health challenge. There were two studies completed over 10
      years ago in Jimma University Specialized Hospital to identify trends, but
      recently there have been many changes in Ethiopia to reduce maternal death.
      Therefore, it is important to track the achievements made in Ethiopia in the
      context of Jimma University Specialized Hospital. No study undertaken in the
      country has quantified deaths of women from specific causes after controlling
      confounders. OBJECTIVE: To assess trends and causes of maternal death in Jimma
      University Specialized Hospital, southwest Ethiopia. METHODS: A time-matched case
      control study was conducted on 600 (120 cases and 480 controls) females who
      utilized obstetrics and gynecology services from January 2010 to December 2014.
      To observe trends in maternal death, maternal mortality ratio was calculated for
      each year. Stata version 13 was used to analyze causal inference using propensity
      score matching method. RESULTS: Maternal mortality ratio was 857/100,000 and had
      a decreasing trend from it's highest in 2010 of 1,873/100,000 to it's lowest of
      350/100,000 in 2014. The leading cause of maternal death was hemorrhage (54%)
      (beta=0.477, 95% confidence interval [CI]: 0.307, 0.647), followed by pregnancy
      induced hypertension (20%) (beta=0.232, 95% CI: 0.046, 0.419), and anemia (12%)
      (beta=0.110, 95% CI: 0.017, 0.204). CONCLUSION: There is a decreasing trend of
      maternal death. Hemorrhage was the major cause of death identified in each year
      of study.

PMID- 28496368
TI  - Self-management and psychological-sexological interventions in patients with
      endometriosis: strategies, outcomes, and integration into clinical care.
AB  - Endometriosis has a multifactorial etiology. The onset and progression of the
      disease are believed to be related to different pathogenic mechanisms. Among
      them, the environment and lifestyle may play significant roles. Diet, dietary
      supplements, physical exercise, osteopathy, massage, acupuncture, transcutaneous
      electrical nerve stimulation, and Chinese herbal medicine may represent a
      complementary and feasible approach in the treatment of symptoms related to the
      disease. In this narrative review, we aimed to examine the most updated evidence
      on these alternative approaches implicated in the self-management of the disease.
      In addition, several studies have demonstrated that endometriosis may negatively
      impact mental health and quality of life, suggesting that affected women may have
      an increased risk of developing psychological suffering as well as sexual
      problems due to the presence of pain. In light of these findings, we discuss the
      importance of integrating psychological interventions (including psychotherapy)
      and sexual therapy in endometriosis treatment.

PMID- 28496371
TI  - Dyschromatosis symmetrica hereditaria with cutaneous lupus erythematosus and
      hyperthyroidism.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a rare genodermatosis
      characterized by various sizes of both hyper- and hypopigmented macules arranged
      in reticulated patterns on the face and the dorsal aspects of the extremities.
      There are also cutaneous and extracutaneous abnormalities, but they are rare. As
      far as we know, DSH associated with immune-mediated conditions has not been
      reported. We report the first case of DSH, which is associated with cutaneous
      lupus erythematosus and hyperthyroidism.

PMID- 28496372
TI  - Choroidal extranodal marginal zone lymphoma diagnosed by full-thickness
      retinochoroidal biopsy: case report and review of the literature.
AB  - The case of an 89-year-old man who was referred for a painless decrease of vision
      in his right eye (RE) is reported. Fundus examination of the RE showed an
      elevated amelanotic lesion located in the posterior pole with an adjacent focal
      round pigmented lesion. There was also a more peripheral amelanotic lesion
      extending from 6 to 9 o'clock clockwise inferotemporally. Uveitis workup and
      imaging studies of brain and orbits were normal. A retinochoroidal biopsy was
      done and showed the presence of choroidal extranodal marginal zone lymphoma. The
      patient was treated with external beam radiotherapy. This report presents a
      review of the literature of all reported cases of choroidal extranodal marginal
      zone lymphoma.

PMID- 28496373
TI  - Multimodal images of chronic branch retinal vein occlusion.
AB  - Two illustrative cases of chronic branch retinal vein occlusion are presented
      with multimodal imaging, including commercially available optical coherence
      tomography angiography. In these two patients, retinal ischemia and collateral
      vessels were well imaged without the need to use traditional fluorescein
      angiography. Optical coherence tomography angiography provides useful information
      for the diagnosis and management of patients with branch retinal vein occlusion
      and other retinal vascular diseases.

PMID- 28496374
TI  - Gender differences and psychological factors associated with suicidal ideation
      among youth in Malaysia.
AB  - Suicide is a global phenomenon that has been showing an upward trend in recent
      years. It is the second leading cause of death among youth. Studies on suicidal
      ideation warrant greater attention, as it leads to suicide attempts and other
      health risk behaviors. Thus, the objective of this study was to compare gender
      differences in suicidal ideation and determine the predictors of suicidal
      ideation among youth. This cross-sectional study was carried out among 232 youths
      aged between 15 and 25 years from selected urban areas in Malaysia. The results
      showed that suicidal ideation was higher among male participants compared with
      female participants. Age was the predictor of suicidal ideation for males, while
      depression and loss of motivation, as components of hopelessness, were the
      predictors of suicidal ideation among females. Hence, it is important that
      professionals conduct early identification tests for suicidality among young
      people. This will facilitate the early detection of depression and hopelessness,
      which is important, in order to prevent suicidal behaviors or other problems
      before these occur.

PMID- 28496375
TI  - Revisiting the etiological aspects of dissociative identity disorder: a
      biopsychosocial perspective.
AB  - Dissociative identity disorder (DID) is a chronic post-traumatic disorder where
      developmentally stressful events in childhood, including abuse, emotional
      neglect, disturbed attachment, and boundary violations are central and typical
      etiological factors. Familial, societal, and cultural factors may give rise to
      the trauma and/or they may influence the expression of DID. Memory and the
      construction of self-identity are cognitive processes that appear markedly and
      centrally disrupted in DID and are related to its etiology. Enduring decoupling
      of psychological modes may create separate senses of self, and metamemory
      processes may be involved in interidentity amnesia. Neurobiological differences
      have been demonstrated between dissociative identities within patients with DID
      and between patients with DID and controls. Given the current evidence, DID as a
      diagnostic entity cannot be explained as a phenomenon created by iatrogenic
      influences, suggestibility, malingering, or social role-taking. On the contrary,
      DID is an empirically robust chronic psychiatric disorder based on
      neurobiological, cognitive, and interpersonal non-integration as a response to
      unbearable stress. While current evidence is sufficient to firmly establish this
      etiological stance, given the wide opportunities for innovative research, the
      disorder is still understudied. Comparison of well-selected samples of DID
      patients with non-dissociative subjects who have other psychiatric disorders
      would further delineate the neurobiological and cognitive features of the
      disorder, whereas genetic research on DID would further illuminate the
      interaction of the individual with environmental stress. As such, DID may be seen
      as an exemplary disease model of the biopsychosocial paradigm in psychiatry.

PMID- 28496376
TI  - Changing trends in residents-as-teachers across graduate medical education.
AB  - BACKGROUND: Teaching residents how to teach is a critical part of residents'
      training in graduate medical education (GME). The purpose of this study was to
      assess the change in resident-as-teacher (RaT) instruction in GME over the past
      15 years in the US. METHODS: We used a quantitative and qualitative survey of all
      program directors (PDs) across specialties. We compared our findings with a
      previous work from 2000-2001 that studied the same matter. Finally, we
      qualitatively analyzed PDs' responses regarding the reasons for implementing and
      not implementing RaT instruction. RESULTS: Two hundred and twenty-one PDs
      completed the survey, which yields a response rate of 12.6%. Over 80% of PDs
      implement RaT, an increase of 26.34% compared to 2000-2001. RaT instruction uses
      multiple methods with didactic lectures reported as the most common, followed by
      role playing in simulated environments, then observing and giving feedback.
      Residents giving feedback, clinical supervision, and bedside teaching were the
      top three targeted skills. Through our qualitative analysis we identified five
      main reasons for implementing RaT: teaching is part of the residents' role;
      learners desire formal RaT training; regulatory bodies require RaT training; RaT
      improves residents' education; and RaT prepares residents for their current and
      future roles. CONCLUSION: The use of RaT instruction has increased significantly
      in GME. More and more PDs are realizing its importance in the residents'
      formative training experience. Future studies should examine the effectiveness of
      each method for RaT instruction.

PMID- 28496377
TI  - Advances in medical education and practice: student perceptions of the flipped
      classroom.

PMID- 28496378
TI  - Ethnopsychiatry fosters creativity and the adoption of critical and reflexive
      thinking in higher education students: insights from a qualitative analysis of a
      preliminary pilot experience at the Faculty of Medicine and Surgery, University
      of Genoa, Italy.
AB  - Creativity is an ability that plays a major role in the modern economy and
      society. It should represent an important component of the medical syllabus.
      However, it is often overlooked by the formal courses at universities. The
      current study aimed at evaluating whether the interactive educational models,
      recently adopted by the Faculty of Medicine and Surgery, at the University of
      Genoa, Italy, would favor the adoption of critical thinking, attitudes to
      changes, cultural diversity acceptance, and the adoption of relational soft
      skills versus traditional and frontal didactic teaching. Thirty students, who
      attended the last year of health care professional course at the Faculty of
      Medicine, volunteered to take part in the study and were randomly allocated to
      two groups: one group receiving an innovative, interactive excellence course and
      the other group receiving a more traditional approach. Ethnopsychiatry was chosen
      as the topic since it was hypothesized that it would have contributed to
      generation of a new approach toward diseases and patients. The first group of
      students, exposed to interactive lectures with the aim of promoting the adoption
      of critical thinking, were more satisfied than the second group. Participants who
      were involved in an active manner and had to work in small groups, actively
      finding their own solutions to solve the problems, perceived the utilized
      teaching method and experience more stimulating, involving, and effective.
      Implications for education policy makers are also envisaged.

PMID- 28496379
TI  - Self-organization of Nucleic Acids in Lipid Constructs.
AB  - Lipids and nucleic acids (NAs) can hierarchically self-organize into a variety of
      nanostructures of increasingly complex geometries such as the 1D lamellar, 2D
      hexagonal, and 3D bicontinuous cubic phases. The diversity and complexity of
      those lipid-NA assemblies are interesting from a fundamental perspective as well
      as being relevant to the performance in gene delivery and gene silencing
      applications. The finding that not only the chemical make of the lipid-NA
      constructs, but their actual supramolecular organization, affects their gene
      transfection and silencing efficiencies has inspired physicists, chemists, and
      engineers to this field of research. At the moment it remains an open question
      how exactly the different lipid-NA structures interact with cells and organelles
      in order to output an optimal response. This article reviews our current
      understanding of the structures of different lipid-NA complexes and the
      corresponding cellular interaction mechanisms. The recent advances in designing
      optimal lipid-based NA carriers will be introduced with an emphasis on the
      structure-function relations.

PMID- 28496380
TI  - Use of the PIXEL method to investigate gas adsorption in metal-organic
      frameworks.
AB  - PIXEL has been used to perform calculations of adsorbate-adsorbent interaction
      energies between a range of metal-organic frameworks (MOFs) and simple guest
      molecules. Interactions have been calculated for adsorption between MOF-5 and Ar,
      H2, and N2; Zn2(BDC)2(TED) (BDC = 1,4-benzenedicarboxylic acid, TED =
      triethylenediamine) and H2; and HKUST-1 and CO2. The locations of the adsorption
      sites and the calculated energies, which show differences in the Coulombic or
      dispersion characteristic of the interaction, compare favourably to experimental
      data and literature energy values calculated using density functional theory.

PMID- 28496381
TI  - Hydrophilic Pt nanoflowers: synthesis, crystallographic analysis and catalytic
      performance.
AB  - Water-soluble Pt nanoflowers (NFs) were prepared by diethylene glycol-mediated
      reduction of Pt acetylacetonate (Pt(acac)2) in the presence of polyethylenimine.
      Advanced electron microscopy analysis showed that the NFs consist of multiple
      branches with a truncated cubic morphology and different crystallographic
      orientations. We demonstrate that the nature of the solvent strongly influences
      the resulting morphology. The catalytic performance of the Pt NFs in 4
      nitrophenol reduction was found to be superior to that of other nanoparticle
      based catalysts. Additionally, the Pt NFs display good catalytic reusability with
      no loss of activity after five consecutive cycles.

PMID- 28496383
TI  - Renata S. Maricevich, MD, and Tuan A. Truong, MD.

PMID- 28496382
TI  - Elements of Family-Centered Care in the Pediatric Intensive Care Unit: An
      Integrative Review.
AB  - This paper reports result from a systematic search and thematic analysis of
      qualitative literature to identify key issues related to family-centered care,
      behaviors, and communication skills that support the parental role and improve
      patient and family outcomes in the PICU. Five themes were identified: 1) sharing
      information; 2) hearing parental voices; 3) making decisions for or with parents;
      4) negotiating roles; and 5) individualizing communication. These themes
      highlight several gaps between how parents want to be involved and perceive
      clinicians engage them in the care of their child. Parental preferences for
      involvement differ in the domains of information sharing, decision making, and
      power-sharing across a spectrum of parental roles from parents as care provider
      to care recipient. The PICU setting may place clinicians in a double bind trying
      to both engage families and protect them from distress. Asking families of
      critically ill children about their preferences for participation across these
      domains may improve clinician-family relationships.

PMID- 28496384
TI  - Facial Trauma.

PMID- 28496385
TI  - Initial Assessment and Evaluation of Traumatic Facial Injuries.
AB  - The care of the facial trauma patient continues to evolve in the ever-changing
      face of medicine. Patients can be reassured that their care is managed by a
      variety of specialists knowledgeable in the assessment and management of complex
      facial injuries. Thanks in part to advances in imaging modalities, bone fixation
      techniques and technology, and a wider array of reconstructive procedures, the
      foundation upon which the reconstructive ladder of facial injuries rests
      continues to expand. The overall goal of repair is a return to a preinjury state
      of form and function.

PMID- 28496386
TI  - Soft Tissue Management in Facial Trauma.
AB  - The management of soft tissue injury after facial trauma poses unique challenges
      to the plastic surgeon, given the specialized nature of facial tissue and the
      aesthetic importance of the face. The general principles of trauma management and
      wound care are applied in all cases. The management of severe injuries to the
      face is discussed in relation to the location and the mechanism of injury. Facial
      transplants have arisen in the past decade for the management of catastrophic
      soft tissue defects, although high morbidity and mortality after these non-life
      saving operations must be considered in patient selection.

PMID- 28496387
TI  - Frontal Sinus Fractures.
AB  - The frontal bone serves a protective role, representing the transition between
      the facial skeleton and the cranium. Within its enclosure, the frontal sinus lies
      adjacent to many important intracranial structures, and injury to this region has
      severe complications if not properly managed. Historically, the goals of frontal
      sinus fracture management have been to best prevent intracranial complications
      with invasive procedures, but a recent shift favoring conservative management now
      aims to preserve the form and function of the frontal sinus and its outflow
      tract. With the advancement of endoscopic techniques and the development of new
      technologies, many alternatives to aggressive surgical management are available.

PMID- 28496388
TI  - Midface Fractures I.
AB  - Facial fractures are a common source of emergency department consultations for
      the plastic surgeon. A working understanding of evaluation, assessment,
      management, and prevention of further injury when dealing with these fractures is
      vital. This two-part series detailing the management of midface fractures serves
      as a guide for the appropriate workup and management of the wide variety of
      fracture patterns that are commonly encountered.

PMID- 28496389
TI  - Midface Fractures II.
AB  - Facial fractures are a common source of emergency department consultations for
      the plastic surgeon. A working understanding of the evaluation, the assessment,
      the management, and the prevention of further injury when dealing with these
      fractures is vital. This second of a two-part series detailing the management of
      midfacial fractures serves as a guide for the appropriate workup and management
      of the wide variety of fracture patterns that are commonly encountered.

PMID- 28496391
TI  - Management of Panfacial Fracture.
AB  - Traumatic panfacial fracture repair is one of the most complex and challenging
      reconstructive procedures to perform. Several principles permeate throughout
      literature regarding the repair of panfacial injuries in a stepwise fashion. The
      primary goal of management in most of these approaches is to restore the occlusal
      relationship at the beginning of sequential repair so that other structures can
      fall into alignment. Through proper positioning of the occlusion and the
      mandibular-maxillary unit with the skull base, the spatial relationships and
      stability of midface buttresses and pillars can then be re-established. Here, the
      authors outline the sequencing of panfacial fracture repair for the restoration
      of anatomical relationships and the optimization of functional and structural
      outcomes.

PMID- 28496392
TI  - Differences in the Management of Pediatric Facial Trauma.
AB  - Craniofacial trauma is common in the pediatric population, with most cases
      limited to soft tissue and dentoalveolar injury. Although facial fractures are
      relatively rare in children compared with adults, they are often associated with
      severe injury and cause significant morbidity and disability. Initial evaluation
      of a child with facial trauma generally involves stabilizing the patient and
      identifying any severe concomitant injuries before diagnosing and managing facial
      injuries. The management of pediatric facial fractures is relatively more
      conservative than that of adults, and nonsurgical management is preferred when
      possible to prevent the disruption of future growth and development. Outcomes
      depend on the site of the injury, management plan, and subsequent growth, so
      children must be followed longitudinally for monitoring and the identification of
      any complications.

PMID- 28496390
TI  - Mandible Fractures.
AB  - Mandible fractures account for a significant portion of maxillofacial injuries
      and the evaluation, diagnosis, and management of these fractures remain
      challenging despite improved imaging technology and fixation techniques.
      Understanding appropriate surgical management can prevent complications such as
      malocclusion, pain, and revision procedures. Depending on the type and location
      of the fractures, various open and closed surgical reduction techniques can be
      utilized. In this article, the authors review the diagnostic evaluation,
      treatment options, and common complications of mandible fractures. Special
      considerations are described for pediatric and atrophic mandibles.

PMID- 28496393
TI  - Subtlety of Ambient-Language Effects in Babbling: A Study of English- and Chinese
      Learning Infants at 8, 10, and 12 Months.
AB  - Prior research on ambient-language effects in babbling has often suggested
      infants produce language-specific phonological features within the first year.
      These results have been questioned in research failing to find such effects and
      challenging the positive findings on methodological grounds. We studied English-
      and Chinese-learning infants at 8, 10, and 12 months and found listeners could
      not detect ambient-language effects in the vast majority of infant utterances,
      but only in items deemed to be words or to contain canonical syllables that may
      have made them sound like words with language-specific shapes. Thus, the present
      research suggests the earliest ambient-language effects may be found in emerging
      lexical items or in utterances influenced by language-specific features of
      lexical items. Even the ambient-language effects for infant canonical syllables
      and words were very small compared with ambient-language effects for meaningless
      but phonotactically well-formed syllable sequences spoken by adult native
      speakers of English and Chinese.

PMID- 28496394
TI  - Triazaspirocycles: Occurrence, Synthesis, and Applications.
AB  - Natural products bearing a triazaspirocyclic motif have received significant
      attention in recent years. These compounds, which feature three nitrogen atoms
      attached to one quaternary carbon forming a spirocyclic scaffold, exhibit a wide
      range of biological activity and have promising applications in materials as well
      as in drug discovery. In this review article, we will discuss triazaspirocycles
      in Nature, their biological activity, and applications. Methods for the synthesis
      of triazaspirocycles as well as the reactivity of triazaspirocyclic scaffolds
      will be reviewed.

PMID- 28496395
TI  - A relative quantitative positive/negative ion switching method for untargeted
      lipidomics via high resolution LC-MS/MS from any biological source.
AB  - INTRODUCTION: Advances in high-resolution mass spectrometry have created renewed
      interest for studying global lipid biochemistry in disease and biological
      systems. OBJECTIVES: Here, we present an untargeted 30 min. LC-MS/MS platform
      that utilizes positive/negative polarity switching to perform unbiased data
      dependent acquisitions (DDA) via higher energy collisional dissociation (HCD)
      fragmentation to profile more than 1000-1500 lipid ions mainly from methyl-tert
      butyl ether (MTBE) or chloroform:methanol extractions. METHODS: The platform uses
      C18 reversed-phase chromatography coupled to a hybrid QExactive Plus/HF Orbitrap
      mass spectrometer and the entire procedure takes ~10 h from lipid extraction to
      identification/quantification for a data set containing 12 samples (~4 h for a
      single sample). Lipids are identified by both accurate precursor ion mass and
      fragmentation features and quantified using Lipid-Search and Elements software.
      RESULTS: Using this approach, we are able to profile intact lipid ions from up to
      18 different main lipid classes and 66 subclasses. We show several studies from
      different biological sources, including cultured cancer cells, resected tissues
      from mice such as lung and breast tumors and biological fluids such as plasma and
      urine. CONCLUSIONS: Using mouse embryonic fibroblasts, we showed that TSC2-/- KD
      significantly abrogates lipid biosynthesis and that rapamycin can rescue
      triglyceride (TG) lipids and we show that SREBP-/- shuts down lipid biosynthesis
      significantly via mTORC1 signaling pathways. We show that in mouse EGFR driven
      lung tumors, a large number of TGs and phosphatidylmethanol (PMe) lipids are
      elevated while some phospholipids (PLs) show some of the largest decrease in
      lipid levels from ~ 2000 identified lipid ions. In addition, we identified more
      than 1500 unique lipid species from human blood plasma.

PMID- 28496396
TI  - Interventions for reducing self-stigma in people with mental illnesses: a
      systematic review of randomized controlled trials.
AB  - Background: Self-stigma occurs when people with mental illnesses internalize
      negative stereotypes and prejudices about their condition. It can reduce help
      seeking behaviour and treatment adherence. The effectiveness of interventions
      aimed at reducing self-stigma in people with mental illness is systematically
      reviewed. Results are discussed in the context of a logic model of the broader
      social context of mental illness stigma. Methods: Medline, Embase, PsycINFO,
      ERIC, and CENTRAL were searched for randomized controlled trials in November
      2013. Studies were assessed with the Cochrane risk of bias tool. Results: Five
      trials were eligible for inclusion, four of which provided data for statistical
      analyses. Four studies had a high risk of bias. The quality of evidence was very
      low for each set of interventions and outcomes. The interventions studied
      included various group based anti-stigma interventions and an anti-stigma
      booklet. The intensity and fidelity of most interventions was high. Two studies
      were considered to be sufficiently homogeneous to be pooled for the outcome self
      stigma. The meta-analysis did not find a statistically significant effect (SMD
      [95% CI] at 3 months: -0.26 [-0.64, 0.12], I2=0%, n=108). None of the individual
      studies found sustainable effects on other outcomes, including recovery, help
      seeking behaviour and self-stigma. Conclusions: The effectiveness of
      interventions against self-stigma is uncertain. Previous studies lacked
      statistical power, used questionable outcome measures and had a high risk of
      bias. Future studies should be based on robust methods and consider practical
      implications regarding intervention development (relevance, implementability, and
      placement in routine services).

PMID- 28496397
TI  - Conflicts at work are associated with a higher risk of cardiovascular disease.
AB  - Background: Only few authors have analyzed the impact of workplace conflicts and
      the resulting stress on the risk of developing cardiovascular disorders. The goal
      of this study was to analyze the association between workplace conflicts and
      cardiovascular disorders in patients treated by German general practitioners.
      Methods: Patients with an initial documentation of a workplace conflict
      experience between 2005 and 2014 were identified in 699 general practitioner
      practices (index date). We included only those who were between the ages of 18
      and 65 years, had a follow-up time of at least 180 days after the index date, and
      had not been diagnosed with angina pectoris, myocardial infarction, coronary
      heart diseases, or stroke prior to the documentation of the workplace mobbing. In
      total, the study population consisted of 7,374 patients who experienced conflicts
      and 7,374 controls for analysis. The main outcome measure was the incidence of
      angina pectoris, myocardial infarction, and stroke correlated with workplace
      conflict experiences. Results: After a maximum of five years of follow-up, 2.9%
      of individuals who experienced workplace conflict were affected by cardiovascular
      diseases, while only 1.4% were affected in the control group (p-value <0.001).
      Workplace conflict was associated with a 1.63-fold increase in the risk of
      developing cardiovascular diseases. Finally, the impact of workplace conflict was
      higher for myocardial infarction (OR=2.03) than for angina pectoris (OR=1.79) and
      stroke (OR=1.56). Conclusions: Overall, we found a significant association
      between workplace conflicts and cardiovascular disorders.

PMID- 28496399
TI  - The Effect of Wealth Shocks on Loss Aversion: Behavior and Neural Correlates.
AB  - Kahneman and Tversky (1979) first demonstrated that when individuals decide
      whether or not to accept a gamble, potential losses receive more weight than
      possible gains in the decision. This phenomenon is referred to as loss aversion.
      We investigated how loss aversion in risky financial decisions is influenced by
      sudden changes to wealth, employing both behavioral and neurobiological measures.
      We implemented an fMRI experimental paradigm, based on that employed by Tom et
      al. (2007). There are two treatments, called RANDOM and CONTINGENT. In RANDOM,
      the baseline setting, the changes to wealth, referred to as wealth shocks in
      economics, are independent of the actual choices participants make. Under
      CONTINGENT, we induce the belief that the changes in income are a consequence of
      subjects' own decisions. The magnitudes and sequence of the shocks to wealth are
      identical between the CONTINGENT and RANDOM treatments. We investigated whether
      more loss aversion existed in one treatment than another. The behavioral results
      showed significantly greater loss aversion in CONTINGENT compared to RANDOM after
      a negative wealth shock. No differences were observed in the response to positive
      shocks. The fMRI results revealed a neural loss aversion network, comprising the
      bilateral striatum, amygdala and dorsal anterior cingulate cortex that was common
      to the CONTINGENT and RANDOM tasks. However, the ventral prefrontal cortex,
      primary somatosensory cortex and superior occipital cortex, showed greater
      activation in response to a negative change in wealth due to individual's own
      decisions than when the change was exogenous. These results indicate that
      striatum activation correlates with loss aversion independently of the source of
      the shock, and that the ventral prefrontal cortex (vPFC) codes the experimental
      manipulation of agency in one's actions influencing loss aversion.

PMID- 28496398
TI  - Growth of Thalamocortical Fibers to the Somatosensory Cortex in the Human Fetal
      Brain.
AB  - Thalamocortical (TH-C) fiber growth begins during the embryonic period and is
      completed by the third trimester of gestation in humans. Here we determined the
      timing and trajectories of somatosensory TH-C fibers in the developing human
      brain. We analyzed the periods of TH-C fiber outgrowth, path-finding, "waiting"
      in the subplate (SP), target selection, and ingrowth in the cortical plate (CP)
      using histological sections from post-mortem fetal brain [from 7 to 34
      postconceptional weeks (PCW)] that were processed with acetylcholinesterase
      (AChE) histochemistry and immunohistochemical methods. Images were compared with
      post mortem diffusion tensor imaging (DTI)-based fiber tractography (code No NO1
      HD-4-3368). The results showed TH-C axon outgrowth occurs as early as 7.5 PCW in
      the ventrolateral part of the thalamic anlage. Between 8 and 9.5 PCW, TH-C axons
      form massive bundles that traverse the diencephalic-telencephalic boundary. From
      9.5 to 11 PCW, thalamocortical axons pass the periventricular area at the pallial
      subpallial boundary and enter intermediate zone in radiating fashion. Between 12
      and 14 PCW, the TH-C axons, aligned along the fibers from the basal forebrain,
      continue to grow for a short distance within the deep intermediate zone and enter
      the deep CP, parallel with SP expansion. Between 14 and 18 PCW, the TH-C
      interdigitate with callosal fibers, running shortly in the sagittal stratum and
      spreading through the deep SP ("waiting" phase). From 19 to 22 PCW, TH-C axons
      accumulate in the superficial SP below the somatosensory cortical area; this
      occurs 2 weeks earlier than in the frontal and occipital cortices. Between 23 and
      24 PCW, AChE-reactive TH-C axons penetrate the CP concomitantly with its initial
      lamination. Between 25 and 34 PCW, AChE reactivity of the CP exhibits an uneven
      pattern suggestive of vertical banding, showing a basic 6-layer pattern. In
      conclusion, human thalamocortical axons show prolonged growth (4 months), and
      somatosensory fibers precede the ingrowth of fibers destined for frontal and
      occipital areas. The major features of growing TH-C somatosensory fiber
      trajectories are fan-like radiation, short runs in the sagittal strata, and
      interdigitation with the callosal system. These results support our hypothesis
      that TH-C axons are early factors in SP and CP morphogenesis and synaptogenesis
      and may regulate cortical somatosensory system maturation.

PMID- 28496400
TI  - LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and
      Dimeric State.
AB  - The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP
      and affects its processing. This is assumed to be mostly caused by the impact of
      LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early
      in the secretory pathway was reported whereat retention of LRP1 in the ER leads
      to decreased APP cell surface levels and in turn, to reduced Abeta secretion.
      Here, we extended the biochemical and immunocytochemical analyses by showing via
      live cell imaging analyses in primary neurons that LRP1 and APP are transported
      only partly in common (one third) but to a higher degree in distinct fast axonal
      transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change
      of APP transport velocities, indicating that LRP1 recruits APP to a specific type
      of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated
      APP transport. We further show that monomeric and dimeric APP exhibit similar
      transport characteristics and that both are affected by LRP1 in a similar way, by
      slowing down APP anterograde transport and increasing its endocytosis rate. In
      line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an
      increase of monomeric and dimeric APP surface localization and in turn
      accelerated shedding by meprin beta and ADAM10. Notably, a choroid plexus
      specific LRP1 knockout caused a much higher secretion of sAPP dimers into the
      cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1
      functions as a sorting receptor for APP, regulating its cell surface localization
      and thereby its processing by ADAM10 and meprin beta, with the latter exhibiting
      a preference for APP in its dimeric state.

PMID- 28496401
TI  - Monitoring the Right Collection: The Central Cholinergic Neurons as an
      Instructive Example.
AB  - Some neurons are more equal than others: neuroscience relies heavily on the
      notion that there is a division of labor among different subtypes of brain cells.
      Therefore, it is important to recognize groups of neurons that participate in the
      same computation or share similar tasks. However, what the best ways are to
      identify such collections is not yet clear. Here, we argue that monitoring the
      activity of genetically defined cell types will lead to new insights about neural
      mechanisms and improve our understanding of disease vulnerability. Through
      highlighting how central cholinergic neurons encode reward and punishment that
      can be captured by a unified framework of reinforcement surprise, we hope to
      provide an instructive example of how studying a genetically defined cell type
      may further our understanding of neural function.

PMID- 28496403
TI  - Hysteresis in Center of Mass Velocity Control during the Stance Phase of
      Treadmill Walking.
AB  - Achieving a soft landing during walking can be quantified by analyzing changes in
      the vertical velocity of the body center of mass (CoM) just prior to the landing
      of the swing limb. Previous research suggests that walking speed and step length
      may predictably influence the extent of this CoM control. Here we ask how stable
      this control is. We altered treadmill walking speed by systematically increasing
      or decreasing it at fixed intervals. We then reversed direction. We hypothesized
      that the control of the CoM vertical velocity during the late stance of the
      walking gait may serve as an order parameter which has an attribute of
      hysteresis. The presence of hysteresis implies that the CoM control is not based
      on simply knowing the current input conditions to predict the output response.
      Instead, there is also the influence of previous speed conditions on the ongoing
      responses. We found that the magnitudes of CoM control were different depending
      on whether the treadmill speed (as the control parameter) was ramped up or down.
      Changes in step length also influenced CoM control. A stronger effect was
      observed when the treadmill speed was speeded up compared to down. However, the
      effect of speed direction remained significant after controlling for step length.
      The hysteresis effect of CoM control as a function of speed history demonstrated
      in the current study suggests that the regulation of CoM vertical velocity during
      late stance is influenced by previous external conditions and constraints which
      combine to influence the desired behavioral outcome.

PMID- 28496404
TI  - GABA Concentrations in the Anterior Cingulate Cortex Are Associated with Fear
      Network Function and Fear Recovery in Humans.
AB  - Relapse of fear after successful treatment is a common phenomenon in patients
      with anxiety disorders. Animal research suggests that the inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA) plays a key role in the
      maintenance of extinguished fear. Here, we combined magnetic resonance
      spectroscopy and functional magnetic resonance imaging to investigate the role of
      GABA in fear recovery in 70 healthy male participants. We associated baseline
      GABA levels in the dorsal anterior cingulate cortex (dACC) to indices of fear
      recovery as defined by changes in skin conductance responses (SCRs), blood oxygen
      level dependent responses, and functional connectivity from fear extinction to
      fear retrieval. The results showed that high GABA levels were associated with
      increased SCRs, enhanced activation of the right amygdala, and reduced amygdala
      ventromedial prefrontal cortex connectivity during fear recovery. Follow-up
      analyses exclusively for the extinction phase showed that high GABA levels were
      associated with reduced amygdala activation and enhanced amygdala-ventromedial
      prefrontal cortex connectivity, despite the absence of correlations between GABA
      and physiological responses. Follow-up analyses for the retrieval phase did not
      show any significant associations with GABA. Together, the association between
      GABA and increases in SCRs from extinction to retrieval, without associations
      during both phases separately, suggests that dACC GABA primarily inhibits the
      consolidation of fear extinction. In addition, the opposite effects of GABA on
      amygdala activity and connectivity during fear extinction compared to fear
      recovery suggest that dACC GABA may initially facilitate extinction learning.

PMID- 28496402
TI  - Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising
      Therapeutic Targets in Psychiatric Illness.
AB  - Corticostriatal circuits through the orbitofrontal cortex (OFC) play key roles in
      complex human behaviors such as evaluation, affect regulation and reward-based
      decision-making. Importantly, the medial and lateral OFC (mOFC and lOFC) circuits
      have functionally and anatomically distinct connectivity profiles which
      differentially contribute to the various aspects of goal-directed behavior. OFC
      corticostriatal circuits have been consistently implicated across a wide range of
      psychiatric disorders, including major depressive disorder (MDD), obsessive
      compulsive disorder (OCD), and substance use disorders (SUDs). Furthermore,
      psychiatric disorders related to OFC corticostriatal dysfunction can be addressed
      via conventional and novel neurostimulatory techniques, including deep brain
      stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial
      magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS).
      Such techniques elicit changes in OFC corticostriatal activity, resulting in
      changes in clinical symptomatology. Here we review the available literature
      regarding how disturbances in mOFC and lOFC corticostriatal functioning may lead
      to psychiatric symptomatology in the aforementioned disorders, and how
      psychiatric treatments may exert their therapeutic effect by rectifying abnormal
      OFC corticostriatal activity. First, we review the role of OFC corticostriatal
      circuits in reward-guided learning, decision-making, affect regulation and
      reappraisal. Second, we discuss the role of OFC corticostriatal circuit
      dysfunction across a wide range of psychiatric disorders. Third, we review
      available evidence that the therapeutic mechanisms of various neuromodulation
      techniques may directly involve rectifying abnormal activity in mOFC and lOFC
      corticostriatal circuits. Finally, we examine the potential of future
      applications of therapeutic brain stimulation targeted at OFC circuitry;
      specifically, the role of OFC brain stimulation in the growing field of
      individually-tailored therapies and personalized medicine in psychiatry.

PMID- 28496406
TI  - Neural Correlates of Phrase Rhythm: An EEG Study of Bipartite vs. Rondo Sonata
      Form.
AB  - This paper introduces the neural correlates of phrase rhythm. In short, phrase
      rhythm is the rhythmic aspect of phrase construction and the relationships
      between phrases. For the sake of establishing the neural correlates, a musical
      experiment has been designed to induce music-evoked stimuli related to phrase
      rhythm. Brain activity is monitored through electroencephalography (EEG) by using
      a brain-computer interface. The power spectral value of each EEG channel is
      estimated to obtain how power variance distributes as a function of frequency.
      Our experiment shows statistical differences in theta and alpha bands in the
      phrase rhythm variations of two classical sonatas, one in bipartite form and the
      other in rondo form.

PMID- 28496405
TI  - Temporal Dynamics of Proactive and Reactive Motor Inhibition.
AB  - Proactive motor inhibition refers to endogenous preparatory mechanisms
      facilitating action inhibition, whereas reactive motor inhibition is considered
      to be a sudden stopping process triggered by external signals. Previous studies
      were inconclusive about the temporal dynamics of involved neurocognitive
      processes during proactive and reactive motor control. Using
      electroencephalography (EEG), we investigated the time-course of proactive and
      reactive inhibition, measuring event-related oscillations and event-related
      potentials (ERPs). Participants performed in a cued go/nogo paradigm with cues
      indicating whether the motor response might or might not have to be inhibited.
      Based on the dual mechanisms of control (DMC) framework by Braver, we
      investigated the role of attentional effects, motor preparation in the
      sensorimotor cortex and prefrontal cognitive control mechanisms, separating
      effects before and after target onset. In the cue-target interval, proactive
      motor inhibition was associated with increased attention, reflected in reduced
      visual alpha power and an increased contingent negative variation (CNV). At the
      same time, motor inhibition was modulated by reduced sensorimotor beta power.
      After target onset, proactive inhibition resulted in an increased N1, indicating
      allocation of attention towards relevant stimuli, increased prefrontal beta power
      and a modulation of sensorimotor mu activity. As in previous studies, reactive
      stopping of motor actions was associated with increased prefrontal beta power and
      increased sensorimotor beta activity. The results stress the relevance of
      attentional mechanisms for proactive inhibition and speak for different
      neurocognitive mechanisms being involved in the early preparation for and in
      later implementation of motor inhibition.

PMID- 28496407
TI  - Unsupervised Idealization of Ion Channel Recordings by Minimum Description
      Length: Application to Human PIEZO1-Channels.
AB  - Researchers can investigate the mechanistic and molecular basis of many
      physiological phenomena in cells by analyzing the fundamental properties of
      single ion channels. These analyses entail recording single channel currents and
      measuring current amplitudes and transition rates between conductance states.
      Since most electrophysiological recordings contain noise, the data analysis can
      proceed by idealizing the recordings to isolate the true currents from the noise.
      This de-noising can be accomplished with threshold crossing algorithms and Hidden
      Markov Models, but such procedures generally depend on inputs and supervision by
      the user, thus requiring some prior knowledge of underlying processes. Channels
      with unknown gating and/or functional sub-states and the presence in the
      recording of currents from uncorrelated background channels present substantial
      challenges to such analyses. Here we describe and characterize an idealization
      algorithm based on Rissanen's Minimum Description Length (MDL) Principle. This
      method uses minimal assumptions and idealizes ion channel recordings without
      requiring a detailed user input or a priori assumptions about channel conductance
      and kinetics. Furthermore, we demonstrate that correlation analysis of
      conductance steps can resolve properties of single ion channels in recordings
      contaminated by signals from multiple channels. We first validated our methods on
      simulated data defined with a range of different signal-to-noise levels, and then
      showed that our algorithm can recover channel currents and their substates from
      recordings with multiple channels, even under conditions of high noise. We then
      tested the MDL algorithm on real experimental data from human PIEZO1 channels and
      found that our method revealed the presence of substates with alternate
      conductances.

PMID- 28496409
TI  - Rapid Screening for alpha-Glucosidase Inhibitors from Gymnema sylvestre by
      Affinity Ultrafiltration-HPLC-MS.
AB  - Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti
      diabetic activity, and the gymnemic acids were reported as the main bioactive
      components in this plant species. However, the specific components responsible
      for the hypoglycemic effect still remain unknown. In the present study, the in
      vitro study revealed that the extract of G. sylvestre exhibited significant
      inhibitory activity against alpha-glucosidase with IC50 at 68.70 +/- 1.22 MUg/mL
      compared to acarbose (positive control) at 59.03 +/- 2.30 MUg/mL, which further
      indicated the potential anti-diabetic activity. To this end, a method based on
      affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF
      HPLC-MS) was established to rapidly screen and identify the alpha-glucosidase
      inhibitors from G. sylvestre. In this way, 9 compounds with higher enrichment
      factors (EFs) were identified according to their MS/MS spectra. Finally, the
      structure-activity relationships revealed that glycosylation could decrease the
      potential antisweet activity of sapogenins, and other components except gymnemic
      acids in G. sylvestre could also be good alpha-glucosidase inhibitors due to
      their synergistic effects. Taken together, the proposed method combing alpha
      glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and
      identifying potential inhibitors of alpha-glucosidase from complex natural
      products, and could be further explored as a valuable high-throughput screening
      (HTS) platform in the early anti-diabetic drug discovery stage.

PMID- 28496408
TI  - The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment.
AB  - Progressive cognitive dysfunction is a central characteristic of diabetic
      encephalopathy (DE). With an aging population, the incidence of DE is rising and
      it has become a major threat that seriously affects public health. Studies within
      this decade have indicated the important role of risk factors such as oxidative
      stress and inflammation on the development of cognitive impairment. With the
      recognition of the two-way communication between gut and brain, recent
      investigation suggests that "microbiota-gut-brain axis" also plays a pivotal role
      in modulating both cognition function and endocrine stability. This review aims
      to systemically elucidate the underlying impact of diabetes on cognitive
      impairment.

PMID- 28496410
TI  - Clinical Applications of Iso-Inertial, Eccentric-Overload (YoYoTM) Resistance
      Exercise.
AB  - In the quest for a viable non-gravity dependent method to "lift weights" in
      space, our laboratory introduced iso-inertial resistance (YoYoTM) exercise using
      spinning flywheel(s), more than 25 years ago. After being thoroughly tested in
      individuals subjected to various established spaceflight analogs, a multi-mode
      YoYoTM exercise apparatus was eventually installed on the International Space
      Station in 2009. The method, applicable to any muscle group, provides
      accommodated resistance and optimal muscle loading through the full range of
      motion of concentric actions, and brief episodes of eccentric overload. This
      exercise intervention has found terrestrial applications and shown success in
      enhancing sports performance and preventing injury and aiding neurological or
      orthopedic rehabilitation. Research has proven that this technique offers unique
      physiological responses not possible with other exercise hardware solutions. This
      paper provides a brief overview of research that has made use, and explored the
      efficacy, of this method in healthy sedentary or physically active individuals
      and populations suffering from muscle wasting, disease or injury. While the
      collective evidence to date suggests YoYoTM offers a potent stimulus to optimize
      the benefits of resistance exercise, systematic research to support clinical use
      of this method has only begun to emerge. Thus, we also offer perspectives on
      unresolved issues, unexplored applications for clinical conditions, and how this
      particular exercise paradigm could be implemented in future clinical research and
      eventually being prescribed. Fields of particular interest are those aimed at
      promoting muscle health by preventing injury or combating muscle wasting and
      neurological or metabolic dysfunction due to aging or illness, or those serving
      in rehabilitation following trauma and/or surgery.

PMID- 28496411
TI  - Calf Compression Sleeves Change Biomechanics but Not Performance and
      Physiological Responses in Trail Running.
AB  - Introduction: The aim of this study was to determine whether calf compression
      sleeves (CS) affects physiological and biomechanical parameters, exercise
      performance, and perceived sensations of muscle fatigue, pain and soreness during
      prolonged (~2 h 30 min) outdoor trail running. Methods: Fourteen healthy trained
      males took part in a randomized, cross-over study consisting in two identical 24
      km trail running sessions (each including one bout of running at constant rate on
      moderately flat terrain, and one period of all-out running on hilly terrain)
      wearing either degressive CS (23 +/- 2 mmHg) or control sleeves (CON, <4 mmHg).
      Running time, heart rate and muscle oxygenation of the medial gastrocnemius
      muscle (measured using portable near-infrared spectroscopy) were monitored
      continuously. Muscle functional capabilities (power, stiffness) were determined
      using 20 s of maximal hopping before and after both sessions. Running
      biomechanics (kinematics, vertical and leg stiffness) were determined at 12 km.h
      1 at the beginning, during, and at the end of both sessions. Exercise-induced
      Achilles tendon pain and delayed onset calf muscles soreness (DOMS) were assessed
      using visual analog scales. Results: Muscle oxygenation increased significantly
      in CS compared to CON at baseline and immediately after exercise (p < 0.05),
      without any difference in deoxygenation kinetics during the run, and without any
      significant change in run times. Wearing CS was associated with (i) higher aerial
      time and leg stiffness in running at constant rate, (ii) with lower ground
      contact time, higher leg stiffness, and higher vertical stiffness in all-out
      running, and (iii) with lower ground contact time in hopping. Significant DOMS
      were induced in both CS and CON (>6 on a 10-cm scale) with no difference between
      conditions. However, Achilles tendon pain was significantly lower after the trial
      in CS than CON (p < 0.05). Discussion: Calf compression did not modify muscle
      oxygenation during ~2 h 30 of trail running but significantly changed running
      biomechanics and lower limb muscle functional capabilities toward a more dynamic
      behavior compared to control session. However, wearing compression sleeves did
      not affect performance and exercise-induced DOMS, while it minimized Achilles
      tendon pain immediately after running.

PMID- 28496412
TI  - Nitric Oxide Synthase Activity Correlates with OGG1 in Ozone-Induced Lung Injury
      Animal Models.
AB  - Background: NO is an important cellular signaling molecule which is derived from
      L-arginine by nitric oxide synthase (NOS) and the effects of NOS signaling in
      lung injury is conflicting. The present study was designed to observe the effect
      of NOS and Arginase signaling in the occurrence and development of lung injury
      and its mechanism. Methods: An ozone-stressed lung injury animal model was
      established by exposure to 2.0 ppm O3 for 30 min every day for consecutive 12 day
      with or without the administration of NO precursor L-arginine or non-selective
      NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME). Then, the lung
      histopathology, the releases of inflammatory mediators and the production of ROS
      were assayed by immunohistochemistry, ELISA and flow cytometry respectively. The
      activities and expression of NOS and Arginase were assayed by biochemical methods
      and western blot. Correspondingly, the release of 8-oxoguanine glycosylase 1(8
      OxoG) and 8-oxoguanine glycosylase 1 (OGG1) were assayed by ELISA and western
      blot. The correlation between NOS/Arginase signaling with 8-OxoG/ OGG1 was also
      analyzed by Pearson correlation coefficients and immunofluorescence in NOS
      deficient bronchial epithelial cells. Results: In ozone-induced rat lung injury
      models, lung inflammation as well as lung architecture was disrupted in a time
      dependent manner. Ozone treatment with L-arginine showed a substantial
      attenuation of adverse lung histopathological changes and treatment with L-NAME
      promoted the inflammation and remodeling. Importantly, the expression of NOS was
      promoted by L-arginine and inhibited by L-NAME and the expression of Arginase was
      promoted by L-NAME treatment. Further, we observed significantly higher levels of
      8-OxoG and lower levels of OGG1 in ozone group which was reversed by L-arginine
      and promoted by L-NAME. The expression of NOS is closely related with 8-OxoG
      /OCG1. Conclusion: These findings give further evidence that the NOS signaling is
      related with base excise repair.

PMID- 28496414
TI  - The Systematic Bias of Ingestible Core Temperature Sensors Requires a Correction
      by Linear Regression.
AB  - An accurate measure of core body temperature is critical for monitoring
      individuals, groups and teams undertaking physical activity in situations of high
      heat stress or prolonged cold exposure. This study examined the range in
      systematic bias of ingestible temperature sensors compared to a certified and
      traceable reference thermometer. A total of 119 ingestible temperature sensors
      were immersed in a circulated water bath at five water temperatures (TEMP A:
      35.12 +/- 0.60 degrees C, TEMP B: 37.33 +/- 0.56 degrees C, TEMP C: 39.48 +/-
      0.73 degrees C, TEMP D: 41.58 +/- 0.97 degrees C, and TEMP E: 43.47 +/- 1.07
      degrees C) along with a certified traceable reference thermometer. Thirteen
      sensors (10.9%) demonstrated a systematic bias > +/-0.1 degrees C, of which 4
      (3.3%) were > +/- 0.5 degrees C. Limits of agreement (95%) indicated that
      systematic bias would likely fall in the range of -0.14 to 0.26 degrees C,
      highlighting that it is possible for temperatures measured between sensors to
      differ by more than 0.4 degrees C. The proportion of sensors with systematic bias
      > +/-0.1 degrees C (10.9%) confirms that ingestible temperature sensors require
      correction to ensure their accuracy. An individualized linear correction achieved
      a mean systematic bias of 0.00 degrees C, and limits of agreement (95%) to 0.00
      0.00 degrees C, with 100% of sensors achieving +/-0.1 degrees C accuracy.
      Alternatively, a generalized linear function (Corrected Temperature ( degrees C)
      = 1.00375 * Sensor Temperature ( degrees C) - 0.205549), produced as the average
      slope and intercept of a sub-set of 51 sensors and excluding sensors with
      accuracy outside +/-0.5 degrees C, reduced the systematic bias to < +/-0.1
      degrees C in 98.4% of the remaining sensors (n = 64). In conclusion, these data
      show that using an uncalibrated ingestible temperature sensor may provide
      inaccurate data that still appears to be statistically, physiologically, and
      clinically meaningful. Correction of sensor temperature to a reference
      thermometer by linear function eliminates this systematic bias (individualized
      functions) or ensures systematic bias is within +/-0.1 degrees C in 98% of the
      sensors (generalized function).

PMID- 28496413
TI  - Cholera Toxin Induces Sustained Hyperexcitability in Myenteric, but Not
      Submucosal, AH Neurons in Guinea Pig Jejunum.
AB  - Background and Aims: Cholera toxin (CT)-induced hypersecretion requires
      activation of secretomotor pathways in the enteric nervous system (ENS). AH
      neurons, which have been identified as a population of intrinsic sensory neurons
      (ISNs), are a source of excitatory input to the secretomotor pathways. We
      therefore examined effects of CT in the intestinal lumen on myenteric and
      submucosal AH neurons. Methods: Isolated segments of guinea pig jejunum were
      incubated for 90 min with saline plus CT (12.5 MUg/ml) or CT + neurotransmitter
      antagonist, or CT + tetrodotoxin (TTX) in their lumen. After washing CT away,
      submucosal or myenteric plexus preparations were dissected keeping
      circumferentially adjacent mucosa intact. Submucosal AH neurons were impaled
      adjacent to intact mucosa and myenteric AH neurons were impaled adjacent to, more
      than 5 mm from, and in the absence of intact mucosa. Neuronal excitability was
      monitored by injecting 500 ms current pulses through the recording electrode.
      Results: After CT pre-treatment, excitability of myenteric AH neurons adjacent to
      intact mucosa (n = 29) was greater than that of control neurons (n = 24), but
      submucosal AH neurons (n = 33, control n = 27) were unaffected. CT also induced
      excitability increases in myenteric AH neurons impaled distant from the mucosa (n
      = 6) or in its absence (n = 5). Coincubation with tetrodotoxin or SR142801 (NK3
      receptor antagonist), but not SR140333 (NK1 antagonist) or granisetron (5-HT3
      receptor antagonist) prevented the increased excitability induced by CT.
      Increased excitability was associated with a reduction in the characteristic AHP
      and an increase in the ADP of these neurons, but not a change in the
      hyperpolarization-activated inward current, Ih . Conclusions: CT increases
      excitability of myenteric, but not submucosal, AH neurons. This is neurally
      mediated and depends on NK3, but not 5-HT3 receptors. Therefore, CT may act to
      amplify the secretomotor response to CT via an increase in the activity of the
      afferent limb of the enteric reflex circuitry.

PMID- 28496415
TI  - Inflammatory Effects of Menthol vs. Non-menthol Cigarette Smoke Extract on Human
      Lung Epithelial Cells: A Double-Hit on TRPM8 by Reactive Oxygen Species and
      Menthol.
AB  - Clinical studies suggest that smokers with chronic obstructive pulmonary disease
      who use menthol cigarettes may display more severe lung inflammation than those
      who smoke non-menthol cigarette. However, the mechanisms for this difference
      remain unclear. Menthol is a ligand of transient receptor potential melastatin-8
      (TRPM8), a Ca2+-permeant channel sensitive to reactive oxygen species (ROS). We
      previously reported that exposure of human bronchial epithelial cells (HBECs) to
      non-menthol cigarette smoke extract (Non-M-CSE) triggers a cascade of
      inflammatory signaling leading to IL-8 induction. In this study, we used this in
      vitro model to compare the inflammatory effects of menthol cigarette smoke
      extract (M-CSE) and Non-M-CSE and delineate the mechanisms underlying the
      differences in their impacts. Compared with Non-M-CSE, M-CSE initially increased
      a similar level of extracellular ROS, suggesting the equivalent oxidant potency.
      However, M-CSE subsequently produced more remarkable elevations in intracellular
      Ca2+, activation of the mitogen-activated protein kinases (MAPKs)/nuclear factor
      kappaB (NF-kappaB) signaling, and IL-8 induction. The extracellular ROS responses
      to both CSE types were totally inhibited by N-acetyl-cysteine (NAC; a ROS
      scavenger). The intracellular Ca2+ responses to both CSE types were also totally
      prevented by NAC, AMTB (a TRPM8 antagonist), or EGTA (an extracellular Ca2+
      chelator). The activation of the MAPK/NF-kappaB signaling and induction of IL-8
      to both CSE types were suppressed to similar levels by NAC, AMTB, or EGTA. These
      results suggest that, in addition to ROS generated by both CSE types, the menthol
      in M-CSE may act as another stimulus to further activate TRPM8 and induce the
      observed responses. We also found that menthol combined with Non-M-CSE induced
      greater responses of intracellular Ca2+ and IL-8 compared with Non-M-CSE alone.
      Moreover, we confirmed the essential role of TRPM8 in these responses to Non-M
      CSE or M-CSE and the difference in these responses between the both CSE types
      using HBECs with TRPM8 knockdown and TRPM8 knockout, and using HEK293 cells
      transfected with hTRPM8. Thus, compared with exposure to Non-M-CSE, exposure to M
      CSE induced greater TRPM8-mediated inflammatory responses in HBECs. These
      augmented effects may be due to a double-hit on lung epithelial TRPM8 by ROS
      generated from CSE and the menthol in M-CSE.

PMID- 28496416
TI  - Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by
      Regulating NF-kappaB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in
      Macrophages.
AB  - Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling
      molecules, participates in formation and disruption of atherosclerotic plaque.
      Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by
      involving in extracellular matrix (ECM) degradation and then thinning fibrous
      cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated
      with coronary plaque instability, but the relationship between LPA and MMP-9
      remains unclear. The present work therefore aimed at elucidating association
      between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in
      macrophages. We found that plasma LPA and MMP-9 levels were correlated positively
      (r = 0.31, P < 0.05) and both elevated significantly in patients with acute
      myocardial infarct (AMI). Consistent with peripheral blood levels, histochemical
      staining indicated that autotaxin (ATX), LPA-producing ectoenzyme, and MMP-9 were
      expressed frequently in the necrotic core and fibrous cap of human unstable
      plaques, which might increase the instability of plaque. Experiments in vitro
      were done with THP-1-derived macrophages and showed that LPA enhanced the
      expression, secretion and activity of MMP-9 in a time- and dose-dependent manner.
      Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral
      blood monocyte-derived macrophages. PDTC, NF-kappaB inhibitor, but not inhibitor
      of AP-1 and PPARgamma, effectively prevented LPA-induced MMP-9 expression and NF
      kappaB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce
      MMP-9 elevation by activating NF-kappaB pathway. In addition, knockdown of LPA2
      attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings
      revealed that LPA upregulated the expression of MMP-9 through activating NF
      kappaB pathway in the LPA2 dependent manner, hence blocking LPA receptors
      signaling may provide therapeutic strategy to target plaque destabilization.

PMID- 28496417
TI  - Corrigendum: Characterization of Reproductive Dormancy in Male Drosophila
      melanogaster.
AB  - [This corrects the article on p. 572 in vol. 7, PMID: 27932997.].

PMID- 28496419
TI  - Comparison and Outcome Analysis of Patients with Takotsubo Cardiomyopathy
      Triggered by Emotional Stress or Physical Stress.
AB  - Background: Previous studies revealed that takotsubo cardiomyopathy (TTC) is
      triggered by physical and emotional stresses. This study was performed to
      determine the short- and long-term prognostic impact of emotional- and physical
      stress associated with TTC. Methods and results: Our institutional database
      constituted a collective of 84 patients diagnosed with TTC between 2003 and 2015.
      The patients were divided into two groups as per the presence of emotional stress
      (n = 24, 21%) or physical stress (n = 60, 52.6%). The endpoint was a composite of
      in-hospital events (thromboembolic events and life-threatening arrhythmias),
      myocardial infarction, all-cause of mortality, re-hospitalization due to heart
      failure, stroke, and recurrence of TTC. A Kaplan-Meier analysis indicated a
      significantly lower event-free survival rate over a mean follow-up of 5 years in
      the emotional group than the physical stress group (log-rank, p < 0.01).
      Multivariate Cox regression analysis revealed only emotional stress (HR 0.4, 95%
      CI: 0.2-0.9, p < 0.05) as a negative independent predictor of the primary
      endpoint. Conclusion: Rates of in-hospital events and short- as well as long-term
      events were significantly lower in TTC patients suffering from emotional stress
      as compared to patients with physical stress.

PMID- 28496420
TI  - Impaired Maintenance of Interpersonal Synchronization in Musical Improvisations
      of Patients with Borderline Personality Disorder.
AB  - Borderline personality disorder (BPD) is a serious and complex mental disorder
      with a lifetime prevalence of 5.9%, characterized by pervasive difficulties with
      emotion regulation, impulse control, and instability in interpersonal
      relationships and self-image. Impairments in interpersonal functioning have
      always been a prominent characteristic of BPD, indicating a need for research to
      identify the specific interpersonal processes that are problematic for diagnosed
      individuals. Previous research has concentrated on self-report questionnaires,
      unidirectional tests, and experimental paradigms wherein the exchange of social
      signals between individuals was not the focus. We propose joint musical
      improvisation as an alternative method to investigate interpersonal processes.
      Using a novel, carefully planned, ABA' accompaniment paradigm, and taking into
      account the possible influences of mood, psychotropic medication, general
      attachment, and musical sophistication, we recorded piano improvisations of 16
      BPD patients and 12 matched healthy controls. We hypothesized that the insecure
      attachment system associated with BPD would be activated in the joint
      improvisation and manifest in measures of timing behavior. Results indicated that
      a logistic regression model, built on differences in timing deviations, predicted
      diagnosis with 82% success. More specifically, over the course of the
      improvisation B section (freer improvisation), controls' timing deviations
      decreased (temporal synchrony became more precise) whereas that of the patients
      with BPD did not, confirming our hypothesis. These findings are in accordance
      with previous research, where BPD is characterized by difficulties in attachment
      relationships such as maintaining strong attachment with others, but it is novel
      to find empirical evidence of such issues in joint musical improvisation. We
      suggest further longitudinal research within the field of music therapy, to study
      how recovery of these timing habits are related to attachment experiences and
      interpersonal functioning in general.

PMID- 28496418
TI  - Toward the Identification of a Specific Psychopathology of Substance Use
      Disorders.
AB  - Addiction is a mental illness in which psychiatric conditions imply a prominent
      burden. Psychopathological symptoms in substance use disorder (SUD) patients are
      usually viewed as being assignable to the sphere of a personality trait or of
      comorbidity, leaving doubts about the presence of a specific psychopathology that
      could only be related to the toxicomanic process. Our research group at the
      University of Pisa has shed light on the possible definition of a specific
      psychopathological dimension in SUDs. In heroin use disorder patients, performing
      an exploratory principal component factor analysis (PCA) on all the 90 items
      included in the SCL-90 questionnaire led to a five-factor solution. The first
      factor accounted for a depressive "worthlessness and being trapped" dimension;
      the second factor picked out a "somatic symptoms" dimension; the third identified
      a "sensitivity-psychoticism" dimension; the fourth a "panic-anxiety" dimension;
      and the fifth a "violence-suicide" dimension. These same results were replicated
      by applying the PCA to another Italian sample of 1,195 heroin addicts entering a
      Therapeutic Community Treatment. Further analyses confirmed the clusters of
      symptoms, independently of demographic and clinical characteristics, active
      heroin use, lifetime psychiatric problems, kind of treatment received, and,
      especially, other substances used by the patient such as alcohol or cocaine.
      Moreover, these clusters were able to discriminate patients affected by addiction
      from those affected by psychiatric diseases such as major depressive disorder.
      Our studies seem to suggest the trait-dependent, rather than the state-dependent,
      nature of the introduced psychopathology dimensions of SUDs.

PMID- 28496421
TI  - The Positivity Bias Phenomenon in Face Perception Given Different Information on
      Ability.
AB  - The negativity bias has been shown in many fields, including in face processing.
      We assume that this bias stems from the potential threat inlayed in the stimuli
      (e.g., negative moral behaviors) in previous studies. In the present study, we
      conducted one behavioral and one event-related potentials (ERPs) experiments to
      test whether the positivity bias rather than negativity bias will arise when
      participants process information whose negative aspect involves no threat, i.e.,
      the ability information. In both experiments, participants first completed a
      valence rating (negative-to-positive) of neutral facial expressions. Further, in
      the learning period, participants associated the neutral faces with high-ability,
      low-ability, or control sentences. Finally, participants rated these facial
      expressions again. Results of the behavioral experiment showed that compared with
      pre-learning, the expressions of the faces associated with high ability sentences
      were classified as more positive in the post-learning expression rating task, and
      the faces associated with low ability sentences were evaluated as more negative.
      Meanwhile, the change in the high-ability group was greater than that of the low
      ability group. The ERP data showed that the faces associated with high-ability
      sentences elicited a larger early posterior negativity, an ERP component
      considered to reflect early sensory processing of the emotional stimuli, than the
      faces associated with control sentences. However, no such effect was found in
      faces associated with low-ability sentences. To conclude, high ability sentences
      exerted stronger influence on expression perception than did low ability ones.
      Thus, we found a positivity bias in this ability-related facial perceptual task.
      Our findings demonstrate an effect of valenced ability information on face
      perception, thereby adding to the evidence on the opinion that person-related
      knowledge can influence face processing. What's more, the positivity bias in non
      threatening surroundings increases scope for studies on processing bias.

PMID- 28496422
TI  - Systematic Observation of an Expert Driver's Gaze Strategy-An On-Road Case Study.
AB  - In this paper we present and qualitatively analyze an expert driver's gaze
      behavior in natural driving on a real road, with no specific experimental task or
      instruction. Previous eye tracking research on naturalistic tasks has revealed
      recurring patterns of gaze behavior that are surprisingly regular and repeatable.
      Lappi (2016) identified in the literature seven "qualitative laws of gaze
      behavior in the wild": recurring patterns that tend to go together, the more so
      the more naturalistic the setting, all of them expected in extended sequences of
      fully naturalistic behavior. However, no study to date has observed all in a
      single experiment. Here, we wanted to do just that: present observations
      supporting all the "laws" in a single behavioral sequence by a single subject. We
      discuss the laws in terms of unresolved issues in driver modeling and open
      challenges for experimental and theoretical development.

PMID- 28496423
TI  - The Inhibitory Mechanism in Learning Ambiguous Words in a Second Language.
AB  - Ambiguous words are hard to learn, yet little is known about what causes this
      difficulty. The current study aimed to investigate the relationship between the
      representations of new and prior meanings of ambiguous words in second language
      (L2) learning, and to explore the function of inhibitory control on L2 ambiguous
      word learning at the initial stage of learning. During a 4-day learning phase,
      Chinese-English bilinguals learned 30 novel English words for 30 min per day
      using bilingual flashcards. Half of the words to be learned were unambiguous (had
      one meaning) and half were ambiguous (had two semantically unrelated meanings
      learned in sequence). Inhibitory control was introduced as a subject variable
      measured by a Stroop task. The semantic representations established for the
      studied items were probed using a cross-language semantic relatedness judgment
      task, in which the learned English words served as the prime, and the targets
      were either semantically related or unrelated to the prime. Results showed that
      response latencies for the second meaning of ambiguous words were slower than for
      the first meaning and for unambiguous words, and that performance on only the
      second meaning of ambiguous words was predicted by inhibitory control ability.
      These results suggest that, at the initial stage of L2 ambiguous word learning,
      the representation of the second meaning is weak, probably interfered with by the
      representation of the prior learned meaning. Moreover, inhibitory control may
      modulate learning of the new meanings, such that individuals with better
      inhibitory control may more effectively suppress interference from the first
      meaning, and thus learn the new meaning more quickly.

PMID- 28496424
TI  - The German Version of the Strengths Use Scale: The Relation of Using Individual
      Strengths and Well-being.
AB  - Theoretical perspectives in positive psychology have considered the possession
      and use of strengths equally but in applied research more studies focused on
      having them, probably due to the absence of psychometrically adequate scales.
      Therefore, the aim of this study was to assess the psychometric characteristics
      of the German language version of the Strengths Use Scale (SUS) and to explore
      relationships between strengths use and several indicator measures of well-being:
      the presence of positive and the absence of negative affect, self-esteem as
      identity aspect, vitality as self-regulatory resource, and stress for capturing
      the evaluation of difficulties and obstacles impinging on well-being. The
      original English version of the SUS was translated following recommended
      independent forward-backward translation techniques. Exploratory and confirmatory
      factor analyses were conducted, including a German-speaking convenience sample of
      university students (N = 374). Additionally, the relations of strengths use and
      well-being indicators were analyzed. Factorial validity revealed a single-factor
      structure of the German version of the SUS, explaining 58.4% variance (factor
      loadings: 0.58 to 0.86), approving the scale's design and showing high internal
      consistency (Cronbach's alpha 0.95). The hypothesized positive relationships of
      strengths use with positive affect, self-esteem, and vitality were confirmed as
      well as the negative relationships with negative affect and stress. The German
      version of the SUS is psychometrically sound and data indicate that individual
      strengths use and well-being related measures interact. The instrument can be
      recommended for future research questions such as if and how the promotion of
      applying individual strengths during education enhances levels of well-being, or
      how the implementation of strengths use in job-design guidelines or working
      conditions can result in higher levels of well-being or healthiness.

PMID- 28496425
TI  - Verbalizations Affect Visuomotor Control in Hitting Objects to Distant Targets.
AB  - There is a long-standing proposal for the existence of two neuroanatomically and
      functionally separate visual systems; one supported by the dorsal pathway to
      control action and the second supported by the ventral pathway to handle explicit
      perceptual judgments. The dorsal pathway requires fast access to egocentric
      information, while the ventral pathway primarily requires allocentric
      information. Despite the evidence for functionally distinct systems, researchers
      have posited important interactions. This paper examines evidence to what degree
      the interaction becomes more important when target-identity, the perception of
      which is supported by the ventral stream, is verbalized during the execution of a
      target-directed far-aiming movement. In the experiment reported here participants
      hit balls toward distant targets while concurrently making explicit perceptual
      judgments of target properties. The endpoint of a shaft served as the target,
      with conditions including illusory arrow fins at the endpoint. Participants
      verbalized the location of the target by comparing it to a reference line and
      calling out "closer" or "further" while propelling the ball to the target. The
      impact velocity at ball contact was compared for hits toward three shafts of
      lengths, 94, 100, and 106 cm, with and without verbalizations and delays. It was
      observed that the meaning of the expressed words modulated movement execution
      when the verbalizations were consistent with the action characteristics. This
      effect of semantic content was evident regardless of target visibility during
      movement execution, demonstrating it was not restricted to movements that rely on
      visual memory. In addition to a direct effect of semantic content we anticipated
      an indirect effect of verbalization to result in action shifting toward the use
      of context-dependent allocentric information. This would result in an illusion
      bias on the impact velocity when the target is embedded in a Muller-Lyer
      configuration. We observed an ubiquitous effect of illusory context on movement
      execution, and not only when verbalizations were made. We suggest that the
      current experimental design with a far-aiming task where most conditions required
      reporting or retaining spatial characteristics of targets for action over time
      may have elicited a strong reliance on allocentric information to guide action.

PMID- 28496426
TI  - Chronic Pain as a Hypothetical Construct: A Practical and Philosophical
      Consideration.
AB  - Pain has been defined by the International Association for the Study of Pain
      (IASP) as "an unpleasant sensory and emotional experience associated with actual
      or potential tissue damage, or described in terms of such damage." Chronic pain
      is usually described as pain that has persisted for 3-6 months and/or beyond the
      expected time of healing. The numerical pain rating (NPR) is the customary metric
      and often considered as a proxy for the subjective experience of chronic pain.
      This definition of pain (chronic) has been of significant heuristic value.
      However, the definition and the models it has spawned tend to encourage the
      interpretation of pain as a measurable entity and implies that the patient's
      experience of pain can be fully comprehended by someone other than the person in
      pain. Several major models of pain have been scrutinized and found to propagate
      the notion of pain as a 'thing' and fall prey to biomedical reductionism and
      Cartesian (mind-body) dualism. Furthermore, the NPR does not appear to capture
      the complexity of chronic pain and correlates poorly with other clinically
      meaningful outcomes. It, and other aspects of the current notion of chronic pain,
      appear to be an extension of our reliance on the philosophical principles of
      reductionism and materialism. These and other shortcomings identified in the IASP
      definition have resulted in an increased interest in a reexamination and possible
      updating of our view of pain (chronic) and its definition. The present paper
      describes an alternative view of pain, in particular chronic pain. It argues that
      chronic pain should be understood as a separate phenomenon from, rather than an
      extension of, acute pain and interpreted as a hypothetical construct (HC). HCs
      are contrasted to intervening variables (IV) and the use of HCs in science is
      illustrated. The acceptance of the principles of nonlinearity and emergence are
      seen as important characteristics. The practical implications and barriers of
      this philosophical shift for assessment, treatment, and education are explored.
      The patient's narrative is presented as a potential source of important
      phenomenological data relating to their 'experience' of pain. It is further
      proposed that educational and academic endeavors incorporate a discussion of the
      process of chronification and the role of complexity theory.

PMID- 28496427
TI  - The Relationship between SES and Reading Comprehension in Chinese: A Mediation
      Model.
AB  - An increasing body of research provides evidence that socioeconomic status (SES)
      was significantly related to children's reading development; however, the
      psychological mechanism underlying the association between them remained an open
      question. The present study is designed to test the hypothesized three-path
      effect of vocabulary knowledge and morphological awareness as mediators between
      SES and sentence reading comprehension in Chinese first-graders. Results of
      mediation model showed that SES exerted its effect on sentence reading
      comprehension through the indirect path via the simple mediating effect of
      morphological awareness and the three-path mediating effect of vocabulary
      knowledge and morphological awareness. The findings highlight a previously
      unidentified mechanism of the relationship between SES and reading comprehension
      in Chinese young children.

PMID- 28496428
TI  - Effect of Cyclosporine on Lesion Growth and Infarct Size within the White and
      Gray Matter.
AB  - BACKGROUND: In a recent trial, cyclosporine A (CsA) failed to reduce infarct size
      in acute stroke patients treated with intravenous thrombolysis. White matter (WM)
      and gray matter (GM) may have distinct vulnerability to ischemia and response to
      therapy. Using final infarct size and lesion growth as endpoints, our objectives
      were to (1) investigate any tissue-specific effect of CsA and (2) compare WM and
      GM response to thrombolysis. MATERIALS AND METHODS: We analyzed 84 patients from
      the randomized and placebo-controlled CsA-Stroke trial, who underwent MRI both on
      admission and at 1 month. Lesion growth was defined voxel-wise as infarcted
      tissue at 1 month with no visible lesion on baseline diffusion-weighted imaging.
      After automatic segmentation of GM/WM, final infarct size and lesion growth were
      compared within the GM and WM. RESULTS: Occlusion level was distal (>M1) in 51%
      of cases. No significant difference in GM/WM proportions was observed within
      final infarcts between treatment groups (P = 0.21). Infarct size within the GM or
      WM was similar between the CsA and control groups [GM: 9.2 (2.4; 22.8) with CsA
      vs 8.9 (3.7; 28.4) mL with placebo, P = 0.74; WM: 9.9 (4.7; 25.4) with CsA vs
      14.1 (5.6; 34.1) mL with placebo, P = 0.26]. There was no significant effect of
      CsA on lesion growth in either the GM or WM. Pooling all patients, a trend for
      increased relative lesion growth in WM compared to GM was observed [49.0% (14.7;
      185.7) vs 43.1% (15.4; 117.1), respectively; P = 0.12]. CONCLUSION: No
      differential effect of CsA was observed between WM and GM. Pooling all patients,
      a trend toward greater lesion growth in WM was observed.

PMID- 28496429
TI  - Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.
AB  - An approximately 24-h biological timekeeping mechanism called the circadian clock
      is present in virtually all light-sensitive organisms from cyanobacteria to
      humans. The clock system regulates our sleep-wake cycle, feeding-fasting,
      hormonal secretion, body temperature, and many other physiological functions.
      Signals from the master circadian oscillator entrain peripheral clocks using a
      variety of neural and hormonal signals. Even centrally controlled internal
      temperature fluctuations can entrain the peripheral circadian clocks. But, unlike
      other chemical reactions, the output of the clock system remains nearly constant
      with fluctuations in ambient temperature, a phenomenon known as temperature
      compensation. In this brief review, we focus on recent advances in our
      understanding of the posttranslational modifications, especially a phosphoswitch
      mechanism controlling the stability of PER2 and its implications for the
      regulation of temperature compensation.

PMID- 28496430
TI  - Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia:
      Potential Implications for Migraine Pain.
AB  - BACKGROUND: Parasympathetic innervation of meninges and ability of carbachol,
      acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests
      contribution of cholinergic mechanisms to primary headaches. However,
      neurochemical mechanisms of cholinergic regulation of peripheral nociception in
      meninges, origin place for headache, are almost unknown. METHODS: Using
      electrophysiology, calcium imaging, immunohistochemistry, and staining of
      meningeal mast cells, we studied effects of cholinergic agents on peripheral
      nociception in rat hemiskulls and isolated trigeminal neurons. RESULTS: Both ACh
      and carbachol significantly increased nociceptive firing in peripheral terminals
      of meningeal trigeminal nerves recorded by local suction electrode. Strong
      nociceptive firing was also induced by nicotine, implying essential role of
      nicotinic AChRs in control of excitability of trigeminal nerve endings.
      Nociceptive firing induced by carbachol was reduced by muscarinic antagonist
      atropine, whereas the action of nicotine was prevented by the nicotinic blocker d
      tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but
      not nicotine induced massive degranulation of meningeal mast cells known to
      release multiple pro-nociceptive mediators. Enzymes terminating ACh action,
      acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in
      perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change
      the firing per se but induced nociceptive activity, sensitive to d-tubocurarine,
      after pretreatment of meninges with the migraine mediator CGRP. This observation
      suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine
      and carbachol induced intracellular Ca2+ transients in trigeminal neurons
      partially overlapping with expression of capsaicin-sensitive TRPV1 receptors.
      CONCLUSION: Trigeminal nerve terminals in meninges, as well as dural mast cells
      and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic
      and muscarinic AChRs, which could be activated by the ACh released from
      parasympathetic nerves. These receptors represent a potential target for novel
      therapeutic interventions in trigeminal pain and probably in migraine.

PMID- 28496431
TI  - Sex Differences in Outcomes among Stroke Survivors with Non-Valvular Atrial
      Fibrillation in China.
AB  - Atrial fibrillation (AF) significantly increases the risk of stroke and disease
      burden and is an established predictor of poor outcomes after stroke. However,
      data regarding sex differences in long-term outcomes following stroke in patients
      with AF are scarce. We thus aimed to assess these differences. We recruited 951
      consecutive patients with acute ischemic stroke and non-valvular atrial
      fibrillation (NVAF) treated at three hospitals in Tianjin, China, from January
      2006 to September 2014. Information regarding stroke subtype, severity, risk
      factors, and outcomes (mortality, dependency, and recurrence) at 3, 12, and 36
      months after stroke was recorded. The prevalence of NVAF was 8.4% overall, with a
      higher frequency in women than in men (11.3 vs. 6.9%, P < 0.001). Among patients
      with NVAF, women were older than men. Women were more likely than men to have
      severe stroke (38.8 vs. 29.5%, P < 0.001), high levels of total cholesterol and
      high- and low-density lipoprotein cholesterol (all P < 0.001), hypertension (69.1
      vs. 61.2%, P = 0.012), dyslipidemia (29.8 vs. 20.7%, P = 0.001), and obesity
      (18.5 vs. 11.6%, P = 0.003); they were less likely than men to be current smokers
      (12.2 vs. 33.6%, P < 0.001) and to consume alcohol (0.9 vs. 13.9%, P < 0.001).
      There were greater risks of dependency and recurrence at 36 months after stroke
      in women than in men [odds ratios (95% confidence intervals), 1.64 (1.02-2.64)
      for dependency, P = 0.043; and 2.03 (1.28-3.20) for recurrence, P = 0.002] after
      adjustment for stroke subtype, severity, and risk factors. These findings suggest
      that it is crucial to emphasize the need for individualized stroke prevention
      education and promotion of healthy lifestyles in order to improve NVAF-related
      stroke outcomes and reduce disease burden in women.

PMID- 28496432
TI  - Vestibular Loss in Older Adults Is Associated with Impaired Spatial Navigation:
      Data from the Triangle Completion Task.
AB  - BACKGROUND: Vestibular inputs have been shown to play a critical role in spatial
      navigation. In this study, we sought to evaluate whether vestibular loss due to
      aging contributes to impaired spatial navigation as measured by the triangle
      completion task (TCT). MATERIALS AND METHODS: We recruited three types of
      participants: young controls <55 years of age, older controls >=55 years of age,
      and older patients from a Neurotology Clinic with evidence of vestibular
      physiologic impairment but who did not have any known vestibular disorder. We
      performed the cervical vestibular-evoked myogenic potential to evaluate saccular
      function and video head impulse testing to quantify horizontal semicircular canal
      vestibulo-ocular reflex gain. To assess spatial navigation ability, we
      administered the TCT, in which participants were conveyed along two segments of a
      pre-drawn triangular path and instructed to complete the final segment
      independently. We measured the angle (degrees) and distance (centimeters) of
      deviation from the correct trajectory. We evaluated the influence of vestibular
      inputs on TCT performance. RESULTS: Forty-eight adults participated in the study
      (mean age: 62.0 years; 52.1% females), including 9 young controls, 15 older
      controls, and 24 clinic patients. Clinic patients had the greatest distance of
      deviation (67.7 cm), followed by older controls (45.4 cm), then young controls
      (27.8 cm; p < 0.01). Similarly, clinic patients had greater rotational angles
      (22.1 degrees ) compared to older (13.3 degrees ) and younger controls (12.4
      degrees ; p < 0.01). Following multivariate linear regression adjusting for
      demographic variables, loss of otolith function was associated with an 18.2 cm
      increase in distance of deviation (95% CI: 15.2-47.4) and a 9.2 degrees  increase
      in rotational angle (95% CI: 3.0-15.5). Abnormal semicircular canal function was
      associated with a 26.0 cm increase in distance of deviation (95% CI: 0.2-51.8)
      and a 10.8 degrees  increase in rotational angle (95% CI: 3.0-15.5). Participants
      with both otolith and canal abnormalities had a larger distance error (beta =
      25.3, 95% CI: 6.2-44.4) and angle of deviation (beta = 18.1, 95% CI: 10.1-26.2)
      than with either condition alone. CONCLUSION: Vestibular loss in older adults was
      associated with poorer performance on a dynamic spatial navigation task relative
      to old and young controls.

PMID- 28496433
TI  - Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of
      Mycobacterium tuberculosis.
AB  - Numerous studies show efflux as a universal bacterial mechanism contributing to
      antibiotic resistance and also that the activity of the antibiotics subject to
      efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless,
      the contribution of efflux to the overall drug resistance levels of clinical
      isolates of Mycobacterium tuberculosis is poorly understood and still is ignored
      by many. Here, we evaluated the contribution of drug efflux plus target-gene
      mutations to the drug resistance levels in clinical isolates of M. tuberculosis.
      A panel of 17 M. tuberculosis clinical strains were characterized for drug
      resistance associated mutations and antibiotic profiles in the presence and
      absence of efflux inhibitors. The correlation between the effect of the efflux
      inhibitors and the resistance levels was assessed by quantitative drug
      susceptibility testing. The bacterial growth/survival vs. growth inhibition was
      analyzed through the comparison between the time of growth in the presence and
      absence of an inhibitor. For the same mutation conferring antibiotic resistance,
      different MICs were observed and the different resistance levels found could be
      reduced by efflux inhibitors. Although susceptibility was not restored, the
      results demonstrate the existence of a broad-spectrum synergistic interaction
      between antibiotics and efflux inhibitors. The existence of efflux activity was
      confirmed by real-time fluorometry. Moreover, the efflux pump genes mmr, mmpL7,
      Rv1258c, p55, and efpA were shown to be overexpressed in the presence of
      antibiotics, demonstrating the contribution of these efflux pumps to the overall
      resistance phenotype of the M. tuberculosis clinical isolates studied,
      independently of the genotype of the strains. These results showed that the drug
      resistance levels of multi- and extensively-drug resistant M. tuberculosis
      clinical strains are a combination between drug efflux and the presence of target
      gene mutations, a reality that is often disregarded by the tuberculosis
      specialists in favor of the almost undisputed importance of antibiotic target
      gene mutations for the resistance in M. tuberculosis.

PMID- 28496435
TI  - Serum Metabolomic Profiling of Piglets Infected with Virulent Classical Swine
      Fever Virus.
AB  - Classical swine fever (CSF) is a highly contagious swine infectious disease and
      causes significant economic losses for the pig industry worldwide. The objective
      of this study was to determine whether small molecule metabolites contribute to
      the pathogenesis of CSF. Birefly, serum metabolomics of CSFV Shimen strain
      infected piglets were analyzed by ultraperformance liquid
      chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI
      Q-TOF/MS) in combination with multivariate statistical analysis. In CSFV-infected
      piglets at days 3 and 7 post-infection changes were found in metabolites
      associated with several key metabolic pathways, including tryptophan catabolism
      and the kynurenine pathway, phenylalanine metabolism, fatty acid and lipid
      metabolism, the tricarboxylic acid and urea cycles, branched-chain amino acid
      metabolism, and nucleotide metabolism. Several pathways involved in energy
      metabolism including fatty acid biosynthesis and beta-oxidation, branched-chain
      amino acid metabolism, and the tricarboxylic acid cycle were significantly
      inhibited. Changes were also observed in several metabolites exclusively
      associated with gut microbiota. The metabolomic profiles indicate that CSFV-host
      gut microbiome interactions play a role in the development of CSF.

PMID- 28496436
TI  - Myxococcus xanthus DK1622 Coordinates Expressions of the Duplicate groEL and
      Single groES Genes for Synergistic Functions of GroELs and GroES.
AB  - Chaperonin GroEL (Cpn60) requires cofactor GroES (Cpn10) for protein refolding in
      bacteria that possess single groEL and groES genes in a bicistronic groESL
      operon. Among 4,861 completely-sequenced prokaryotic genomes, 884 possess
      duplicate groEL genes and 770 possess groEL genes with no neighboring groES. It
      is unclear whether stand-alone groEL requires groES in order to function and, if
      required, how duplicate groEL genes and unequal groES genes balance their
      expressions. In Myxococcus xanthus DK1622, we determined that, while duplicate
      groELs were alternatively deletable, the single groES that clusters with groEL1
      was essential for cell survival. Either GroEL1 or GroEL2 required interactions
      with GroES for in vitro and in vivo functions. Deletion of groEL1 or groEL2
      resulted in decreased expressions of both groEL and groES; and ectopic
      complementation of groEL recovered not only the groEL but also groES expressions.
      The addition of an extra groES gene upstream groEL2 to form a bicistronic operon
      had almost no influence on groES expression and the cell survival rate, whereas
      over-expression of groES using a self-replicating plasmid simultaneously
      increased the groEL expressions. The results indicated that M. xanthus DK1622
      cells coordinate expressions of the duplicate groEL and single groES genes for
      synergistic functions of GroELs and GroES. We proposed a potential regulation
      mechanism for the expression coordination.

PMID- 28496434
TI  - A Critical Assessment of the Microorganisms Proposed to be Important to Enhanced
      Biological Phosphorus Removal in Full-Scale Wastewater Treatment Systems.
AB  - Understanding the microbiology of phosphorus (P) removal is considered essential
      to knowledge-based optimization of enhanced biological P removal (EBPR) systems.
      Biological P removal is achieved in these systems by promoting the growth of
      organisms collectively known as the polyphosphate accumulating organisms (PAOs).
      Also considered important to EBPR are the glycogen accumulating organisms (GAOs),
      which are theorized to compete with the PAOs for resources at the expense of P
      removal efficiency. Numerous studies have sought to identify the PAOs and their
      GAOs competitors, with several candidates proposed for each over the last few
      decades. The current study collectively assessed the abundance and diversity of
      all proposed PAOs and GAOs in 18 Danish full-scale wastewater treatment plants
      with well-working biological nutrient removal over a period of 9 years using 16S
      rRNA gene amplicon sequencing. The microbial community structure in all plants
      was relatively stable over time. Evidence for the role of the proposed PAOs and
      GAOs in EBPR varies and is critically assessed, in light of their calculated
      amplicon abundances, to indicate which of these are important in full-scale
      systems. Bacteria from the genus Tetrasphaera were the most abundant of the PAOs.
      The "Candidatus Accumulibacter" PAOs were in much lower abundance and appear to
      be biased by the amplicon-based method applied. The genera Dechloromonas,
      Microlunatus, and Tessaracoccus were identified as abundant putative PAO that
      require further research attention. Interestingly, the actinobacterial
      Micropruina and sbr-gs28 phylotypes were among the most abundant of the putative
      GAOs. Members of the genera Defluviicoccus, Propionivibrio, the family
      Competibacteraceae, and the spb280 group were also relatively abundant in some
      plants. Despite observed high abundances of GAOs (periodically exceeding 20% of
      the amplicon reads), P removal performance was maintained, indicating that these
      organisms were not outcompeting the PAOs in these EBPR systems. Phylogenetic
      diversity within each of the PAOs and GAOs genera was observed, which is
      consistent with reported metabolic diversity for these. Whether or not key traits
      can be assigned to sub-genus level clades requires further investigation.

PMID- 28496437
TI  - Bacillus anthracis Peptidoglycan Integrity Is Disrupted by the Chemokine CXCL10
      through the FtsE/X Complex.
AB  - The antimicrobial activity of the chemokine CXCL10 against vegetative cells of
      Bacillus anthracis occurs via both bacterial FtsE/X-dependent and-independent
      pathways. Previous studies established that the FtsE/X-dependent pathway was
      mediated through interaction of the N-terminal region(s) of CXCL10 with a
      functional FtsE/X complex, while the FtsE/X-independent pathway was mediated
      through the C-terminal alpha-helix of CXCL10. Both pathways result in cell lysis
      and death of B. anthracis. In other bacterial species, it has been shown that
      FtsE/X is involved in cellular elongation though activation of complex-associated
      peptidoglycan hydrolases. Thus, we hypothesized that the CXCL10-mediated killing
      of vegetative cells of B. anthracis through the FtsE/X-dependent pathway resulted
      from the disruption of peptidoglycan processing. Immunofluorescence microscopy
      studies using fluorescent peptidoglycan probes revealed that incubation of B.
      anthracis Sterne (parent) strain with CXCL10 or a C-terminal truncated CXCL10
      (CTTC) affected peptidoglycan processing and/or incorporation of precursors into
      the cell wall. B. anthracis DeltaftsX or ftsE(K123A/D481N) mutant strains, which
      lacked a functional FtsE/X complex, exhibited little to no evidence of disruption
      in peptidoglycan processing by either CXCL10 or CTTC. Additional studies
      demonstrated that the B. anthracis parent strain exhibited a statistically
      significant increase in peptidoglycan release in the presence of either CXCL10 or
      CTTC. While B. anthracis DeltaftsX strain showed increased peptidoglycan release
      in the presence of CXCL10, no increase was observed with CTTC, suggesting that
      the FtsE/X-independent pathway was responsible for the activity observed with
      CXCL10. These results indicate that FtsE/X-dependent killing of vegetative cells
      of B. anthracis results from a loss of cell wall integrity due to disruption of
      peptidoglycan processing and suggest that FtsE/X may be an important
      antimicrobial target to study in the search for alternative microbial
      therapeutics.

PMID- 28496438
TI  - Identification of Cleavage Sites Recognized by the 3C-Like Cysteine Protease
      within the Two Polyproteins of Strawberry Mottle Virus.
AB  - Strawberry mottle virus (SMoV, family Secoviridae, order Picornavirales) is one
      of several viruses found in association with strawberry decline disease in
      Eastern Canada. The SMoV genome consists of two positive-sense single-stranded
      RNAs, each encoding one large polyprotein. The RNA1 polyprotein (P1) includes the
      domains for a putative helicase, a VPg, a 3C-like cysteine protease and an RNA
      dependent RNA polymerase at its C-terminus, and one or two protein domains at its
      N-terminus. The RNA2 polyprotein (P2) is predicted to contain the domains for a
      movement protein (MP) and one or several coat proteins at its N-terminus, and one
      or more additional domains for proteins of unknown function at its C-terminus.
      The RNA1-encoded 3C-like protease is presumed to cleave the two polyproteins in
      cis (P1) and in trans (P2). Using in vitro processing assays, we systematically
      scanned the two polyproteins for cleavage sites recognized by this protease. We
      identified five cis-cleavage sites in P1, with cleavage between the putative
      helicase and VPg domains being the most efficient. The presence of six protein
      domains in the SMoV P1, including two upstream of the putative helicase domain,
      is a feature shared with nepoviruses but not with comoviruses. Results from trans
      cleavage assays indicate that the RNA1-encoded 3C-like protease recognized a
      single cleavage site, which was between the predicted MP and coat protein domains
      in the P2 polyprotein. The cleavage site consensus sequence for the SMoV 3C-like
      protease is AxE (E or Q)/(G or S).

PMID- 28496439
TI  - Bortezomib Warhead-Switch Confers Dual Activity against Mycobacterial
      Caseinolytic Protease and Proteasome and Selectivity against Human Proteasome.
AB  - Mycobacteria harbor two main degradative proteolytic machineries, the
      caseinolytic protease ClpP1P2 and a proteasome. We recently showed that
      Bortezomib inhibits ClpP1P2 and exhibits whole cell activity against
      Mycobacterium tuberculosis. Bortezomib, a dipeptide with a boronic acid warhead,
      is a human proteasome inhibitor approved for cancer therapy. The boronic acid
      warhead of the compound has been shown to drive potency against both the human
      proteasome and ClpP1P2 protease. Selectivity for the bacterial ClpP1P2 protease
      over the human proteasome is lacking but needs to be achieved to move this new
      anti-tuberculosis lead forward. In this study we explored whether an alternative
      warhead could influence Bortezomib's selectivity. We synthesized an analog
      containing a chloromethyl ketone instead of the boronic acid warhead and
      determined potencies against the bacterial and human enzymes. Surprisingly, the
      analog retained activity against mycobacterial ClpP1P2 and was active against the
      mycobacterial proteasome, but was devoid of activity against the human
      proteasome. Interrogation of a set of chloromethyl ketone peptides identified
      three additional compounds similarly inhibiting both ClpP1P2 and the proteasome
      in the bacteria while leaving the human proteasome untouched. Finally, we showed
      that these compounds display bactericidal activity against M. tuberculosis with
      cytotoxicity ranging from acceptable to undetectable. These results suggest that
      selectivity over the human proteasome is achievable. Selectivity, together with
      dual-targeting of mycobacterial ClpP1P2 and proteasome makes this new scaffold an
      attractive starting point for optimization.

PMID- 28496440
TI  - FCgamma Chimeric Receptor-Engineered T Cells: Methodology, Advantages,
      Limitations, and Clinical Relevance.
AB  - For many years, disappointing results have been generated by many investigations,
      which have utilized a variety of immunologic strategies to enhance the ability of
      a patient's immune system to recognize and eliminate malignant cells. However, in
      recent years, immunotherapy has been used successfully for the treatment of
      hematologic and solid malignancies. The impressive clinical responses observed in
      many types of cancer have convinced even the most skeptical clinical oncologists
      that a patient's immune system can recognize and reject his tumor if appropriate
      strategies are implemented. The success immunotherapy is due to the development
      of at least three therapeutic strategies. They include tumor-associated antigen
      (TAA)-specific monoclonal antibodies (mAbs), T cell checkpoint blockade, and TAA
      specific chimeric antigen receptors (CARs) T cell-based immunotherapy. However,
      the full realization of the therapeutic potential of these approaches requires
      the development of strategies to counteract and overcome some limitations. They
      include off-target toxicity and mechanisms of cancer immune evasion, which
      obstacle the successful clinical application of mAbs and CAR T cell-based
      immunotherapies. Thus, we and others have developed the Fc gamma chimeric
      receptors (Fcgamma-CRs)-based strategy. Like CARs, Fcgamma-CRs are composed of an
      intracellular tail resulting from the fusion of a co-stimulatory molecule with
      the T cell receptor zeta chain. In contrast, the extracellular CAR single-chain
      variable fragment (scFv), which recognizes the targeted TAA, has been replaced
      with the extracellular portion of the FcgammaRIIIA (CD16). Fcgamma-CR T cells
      have a few intriguing features. First, given in combination with mAbs, Fcgamma-CR
      T cells mediate anticancer activity in vitro and in vivo by an antibody-mediated
      cellular cytotoxicity mechanism. Second, CD16-CR T cells can target multiple
      cancer types provided that TAA-specific mAbs with the appropriate specificity are
      available. Third, the off-target effect of CD16-CR T cells may be controlled by
      withdrawing the mAb administration. The goal of this manuscript was threefold.
      First, we review the current state-of-the-art of preclinical CD16-CR T cell
      technology. Second, we describe its in vitro and in vivo antitumor activity.
      Finally, we compare the advantages and limitations of the CD16-CR T cell
      technology with those of CAR T cell methodology.

PMID- 28496442
TI  - A Proteomic Study of Hemocyte Proteins from Mud Crab (Scylla paramamosain)
      Infected with White Spot Syndrome Virus or Vibrio alginolyticus.
AB  - In this study, we investigated the hemocytes' immune response to white spot
      syndrome virus (WSSV) or Vibrio alginolyticus infection at the protein level. The
      differential proteomes from crab hemocytes infected with WSSV or V. alginolyticus
      were analyzed using the isobaric tags for relative and absolute quantitation
      approach immediately after infection. Using this approach, we identified 1,799
      proteins by their by LC-MS/MS spectra and sequencing data. These included 157
      upregulated proteins and 164 downregulated proteins after WSSV infection.
      Similarly, 243 proteins were determined to be differentially expressed during V.
      alginolyticus infection, of these, 121 were upregulated and 122 were
      downregulated after infection. Interestingly, among these differentially
      expressed proteins, 106 were up- or downregulated significantly in both WSSV and
      V. alginolyticus infection. Six genes, beta-actin, myosin-9, anti
      lipopolysaccharide factor isoform 4, anti-lipopolysaccharide factor 4,
      transketolase-like protein 2-like isoform 1, and sarcoplasmic calcium-binding
      protein 1 were chosen for further study. The expression of these genes all showed
      a trend of upregulation at 24 h post-WSSV or V. alginolyticus infection except
      for myosin-9 in response to WSSV. To confirm the protective effects of the six
      genes, crabs were injected with specific dsRNAs before WSSV or V. alginolyticus
      challenge. The results showed that the knockdown of these genes led to an
      increase in the morbidity and mortality (P < 0.01) rate, and a decrease in
      infection time in WSSV-infected crabs. During the first 84 h, knockdown of these
      genes also led to an increase in the morbidity rates in V. alginolyticus 
      infected crabs, and results of four genes showed a higher mortality rate than
      that of the control after they were knocked down. This is the first report of the
      proteome response in crab hemocytes during WSSV or V. alginolyticus infection.
      These findings will contribute to our understanding of the immune response to
      WSSV and V. alginolyticus infection in crabs.

PMID- 28496441
TI  - Discovery of Novel Leptospirosis Vaccine Candidates Using Reverse and Structural
      Vaccinology.
AB  - Leptospira spp. are diderm (two membranes) bacteria that infect mammals causing
      leptospirosis, a public health problem with global implications. Thousands of
      people die every year due to leptospirosis, especially in developing countries
      with tropical climates. Prophylaxis is difficult due to multiple factors,
      including the large number of asymptomatic hosts that transmit the bacteria, poor
      sanitation, increasing numbers of slum dwellers, and the lack of an effective
      vaccine. Several leptospiral recombinant antigens were evaluated as a replacement
      for the inactivated (bacterin) vaccine; however, success has been limited. A
      prospective vaccine candidate is likely to be a surface-related protein that can
      stimulate the host immune response to clear leptospires from blood and organs. In
      this study, a comprehensive bioinformatics approach based on reverse and
      structural vaccinology was applied toward the discovery of novel leptospiral
      vaccine candidates. The Leptospira interrogans serovar Copenhageni strain L1-130
      genome was mined in silico for the enhanced identification of conserved beta
      barrel (betab) transmembrane proteins and outer membrane (OM) lipoproteins.
      Orthologs of the prospective vaccine candidates were screened in the genomes of
      20 additional Leptospira spp. Three-dimensional structural models, with a high
      degree of confidence, were created for each of the surface-exposed proteins.
      Major histocompatibility complex II (MHC-II) epitopes were identified, and their
      locations were mapped on the structural models. A total of 18 betab transmembrane
      proteins and 8 OM lipoproteins were identified. These proteins were conserved
      among the pathogenic Leptospira spp. and were predicted to have epitopes for
      several variants of MHC-II receptors. A structural and functional analysis of the
      sequence of these surface proteins demonstrated that most betab transmembrane
      proteins seem to be TonB-dependent receptors associated with transportation.
      Other proteins identified included, e.g., TolC efflux pump proteins, a BamA-like
      OM component of the betab transmembrane protein assembly machinery, and the LptD
      like LPS assembly protein. The structural mapping of the immunodominant epitopes
      identified the location of conserved, surface-exposed, immunogenic regions for
      each vaccine candidate. The proteins identified in this study are currently being
      evaluated for experimental evidence for their involvement in virulence, disease
      pathogenesis, and physiology, in addition to vaccine development.

PMID- 28496443
TI  - Higher Levels of Secretory IgA Are Associated with Low Disease Activity Index in
      Patients with Reactive Arthritis and Undifferentiated Spondyloarthritis.
AB  - INTRODUCTION: Both reactive arthritis (ReA) and undifferentiated
      spondyloarthritis (uSpA) belong to the group of autoinflammatory diseases called
      spondyloarthritis (SpA). Hypotheses have been proposed about a relationship
      between the intestinal mucosa and inflammation of joint tissues. The role of
      immunoglobulin IgA or secretory immunoglobulin A (SIgA) in the inflammatory
      and/or clinical activity of patients with SpA remains poorly understood.
      OBJECTIVE: To evaluate the status of total IgA and SIgA, and the association
      among the levels of SIgA, IgA, IgA anti-Chlamydia trachomatis, and anti-Shigella
      spp. with the disease activity measures, erythrocyte sedimentation rate (ESR) and
      C-reactive protein (CRP) levels, was compared in a cohort of patients with ReA
      and uSpA and healthy subjects. METHODS: This was a cross-sectional study. The
      serum concentrations of SIgA, IgA anti-C. trachomatis, anti-Shigella spp., and
      total IgA were measured. Disease activity was measured in each patient by means
      of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing
      Spondylitis Disease Activity Score (ASDAS). Statistical analysis did include as
      bivariate evaluation, comparisons by Student's t-test, Kruskal-Wallis test, and U
      Mann-Whitney test, with a multivariate evaluation by principal components
      analysis (PCA). A correlation analysis was carried out using the Pearson
      correlation coefficient and a linear regression models. All analysis were made
      using Stata version 11.2(r) for Windows, R V3.3.21. Statistical significance was
      defined a p-value <0.05. RESULTS: In all, 46 patients (78.2% men; mean age, 34.8
      +/- 12.3 years) and 53 controls (41% men; mean age, 32 +/- 11.4 years) were
      included in the study. The mean serum levels of SIgA were higher in SpA patients
      than in healthy subjects (p < 0.001). Only SIgA levels correlated with disease
      activity: BASDAI (r = -0.42, p = 0.0046), ASDAS-CRP (r = -0.37, p = 0.014), and
      ASDAS-ESR (r = -0.45, p = 0.0021). The negative correlation between SIgA and all
      activity indices was higher in HLA-B27-positive patients (BASDAI r = -0.70, p =
      0.0009, ASDAS-CRP r = -0.58, p = 0.0093, and ASDAS-ESR r = -0.57, p = 0.0083).
      The PCA showed three factors: the first component was constituted by variables
      referred as clinical activity measures, the second did include the serological
      activity markers, and the last component was compounded by age and symptoms time.
      CONCLUSION: Elevated serum levels of SIgA were found to be related with low
      disease activity in patients with ReA and uSpA.

PMID- 28496444
TI  - The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper
      T Cells.
AB  - Follicular helper T cells (Tfh) have been identified as the primary cell
      subpopulation regulating B cell responses in germinal centers, thus supporting
      high-affinity antibody production. Among the transcription factors orchestrating
      Tfh cell differentiation and function, the role played by the proto-oncogene c
      Maf remains poorly characterized. We report herein that selective loss of c-Maf
      expression in the T cell compartment results in defective development of Tfh
      cells in response to both antigen/adjuvant vaccinations and commensal intestinal
      bacteria. Accordingly, c-Maf expression in T cells was essential for the
      development and high-affinity antibody secretion in vaccinated animals. c-Maf was
      expressed early, concomitantly to BCL6, in Tfh cell precursors and found to
      regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a
      novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and
      the regulation of humoral immune responses to T-cell-dependent antigens.

PMID- 28496446
TI  - Toward an Inclusive, Congruent, and Precise Definition of Autoinflammatory
      Diseases.
AB  - Autoinflammatory disease was introduced as a concept in 1999, demarcating an
      entirely new group of diseases in clinical, immunological, and conceptual terms.
      During recent years, the preconditions for the definition of autoinflammatory
      conditions have changed. This includes the recent discovery of a number of
      monogenic autoinflammatory conditions with complex phenotypes that combine
      autoinflammation with defects of the adaptive and/or innate immune system,
      resulting in the occurrence of infection, autoimmunity, and/or uncontrolled
      hyperinflammation in addition to autoinflammation. Further, there are strong
      indications that classical IL-1-driven autoinflammatory diseases are associated
      with activation of adaptive immunity. As suggested by this development, we are of
      the opinion that an all-encompassing definition of autoinflammatory diseases
      should regard autoinflammatory conditions and innate dysregulation as inseparable
      and integral parts of the immune system as a whole. Hence, in this article, we
      try to advance the conceptual understanding of autoinflammatory disease by,
      proposing a modification of the definition by Daniel Kastner et al., which allows
      for a congruent and precise description of conditions that expand the
      immunological spectrum of autoinflammatory disease.

PMID- 28496448
TI  - Corrigendum: ACKR2: An Atypical Chemokine Receptor Regulating Lymphatic Biology.
AB  - [This corrects the article on p. 691 in vol. 7, PMID: 28123388.].

PMID- 28496447
TI  - Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via
      Adenosine Receptors.
AB  - INTRODUCTION: Many antitumor therapies induce apoptotic cell death in order to
      cause tumor regression. Paradoxically, apoptotic cells are also known to promote
      wound healing, cell proliferation, and tumor cell repopulation in multicellular
      organisms. We aimed to characterize the nature of the regenerative signals
      concentrated in the micromilieu of dead and dying cells. METHODS: Cultures of
      viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast
      like synoviocytes (FLS) in the presence of dead and dying cells, their
      supernatants (SNs), or purified agonists and antagonists were used to evaluate
      the stimulation of proliferation. Viable cell quantification was performed by
      either flow cytometry of harvested cells or by crystal violet staining of
      adherent cells. High-performance liquid chromatography and liquid chromatography
      coupled with mass spectrometry of cell SNs were deployed to identify the nature
      of growth-promoting factors. Coimplantation of living cells in the presence of
      SNs collected from dead and dying cells and specific agonists was used to
      evaluate tumor growth in vivo. RESULTS: The stimulation of proliferation of few
      surviving cells by bystander dead cells was confirmed for melanoma cells, mouse
      fibroblasts, and primary FLS. We found that small soluble molecules present in
      the protein-free fraction of SNs of dead and dying cells were responsible for the
      promotion of proliferation. The nucleoside inosine released by dead and dying
      cells acting via adenosine receptors was identified as putative inducer of
      proliferation of surviving tumor cells after irradiation and heat treatment.
      CONCLUSION: Inosine released by dead and dying cells mediates tumor cell
      proliferation via purinergic receptors. Therapeutic strategies surmounting this
      pathway may help to reduce the rate of recurrence after radio- and chemotherapy.

PMID- 28496449
TI  - Differences in Flower Transcriptome between Grapevine Clones Are Related to Their
      Cluster Compactness, Fruitfulness, and Berry Size.
AB  - Grapevine cluster compactness has a clear impact on fruit quality and health
      status, as clusters with greater compactness are more susceptible to pests and
      diseases and ripen more asynchronously. Different parameters related to
      inflorescence and cluster architecture (length, width, branching, etc.),
      fruitfulness (number of berries, number of seeds) and berry size (length, width)
      contribute to the final level of compactness. From a collection of 501 clones of
      cultivar Garnacha Tinta, two compact and two loose clones with stable differences
      for cluster compactness-related traits were selected and phenotyped. Key organs
      and developmental stages were selected for sampling and transcriptomic analyses.
      Comparison of global gene expression patterns in flowers at the end of bloom
      allowed identification of potential gene networks with a role in determining the
      final berry number, berry size and ultimately cluster compactness. A large
      portion of the differentially expressed genes were found in networks related to
      cell division (carbohydrates uptake, cell wall metabolism, cell cycle, nucleic
      acids metabolism, cell division, DNA repair). Their greater expression level in
      flowers of compact clones indicated that the number of berries and the berry size
      at ripening appear related to the rate of cell replication in flowers during the
      early growth stages after pollination. In addition, fluctuations in auxin and
      gibberellin signaling and transport related gene expression support that they
      play a central role in fruit set and impact berry number and size. Other
      hormones, such as ethylene and jasmonate may differentially regulate indirect
      effects, such as defense mechanisms activation or polyphenols production. This is
      the first transcriptomic based analysis focused on the discovery of the
      underlying gene networks involved in grapevine traits of grapevine cluster
      compactness, berry number and berry size.

PMID- 28496450
TI  - High-Density Genetic Map Construction and Gene Mapping of Basal Branching Habit
      and Flowers per Leaf Axil in Sesame.
AB  - A good genetic map can provide the framework for quantitative trait loci (QTL)
      analysis, map-based gene cloning, and genome sequence assembling. The main
      objectives of this study were to develop a high-density genetic linkage map using
      specific length amplified fragment sequencing (SLAF-seq) in sesame. In the
      result, a high-resolution genetic map with 9,378 SLAF markers and 13 linkage
      groups (LGs) was constructed. The map spanned a total genetic distance of
      1,974.23 cM, and the mean LG length was 151.86 cM, with an average genetic
      distance of 0.22 cM between adjacent markers. Based on the newly constructed
      genetic map, genes for basal branching habit (SiBH) and flowers per leaf axil
      (SiFA) were mapped to LG5 and LG11, respectively.

PMID- 28496445
TI  - Eosinophils in Autoimmune Diseases.
AB  - Eosinophils are multifunctional granulocytes that contribute to initiation and
      modulation of inflammation. Their role in asthma and parasitic infections has
      long been recognized. Growing evidence now reveals a role for eosinophils in
      autoimmune diseases. In this review, we summarize the function of eosinophils in
      inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune
      myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with
      polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil
      targeted therapies, and experimental models have contributed to our understanding
      of the regulation and function of eosinophils in these diseases. By examining the
      role of eosinophils in autoimmune diseases of different organs, we can identify
      common pathogenic mechanisms. These include degranulation of cytotoxic granule
      proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of
      proteases degrading extracellular matrix, immune modulation through cytokines,
      antigen presentation, and prothrombotic functions. The association of
      eosinophilic diseases with autoimmune diseases is also examined, showing a
      possible increase in autoimmune diseases in patients with eosinophilic
      esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we
      summarize key future research needs.

PMID- 28496452
TI  - Transcriptome Analyses Reveal Candidate Pod Shattering-Associated Genes Involved
      in the Pod Ventral Sutures of Common Vetch (Vicia sativa L.).
AB  - The seed dispersion caused by pod shattering is a form of propagation used by
      many wild species. Loss of seeds from pod shattering is frequent in the common
      vetch (Vicia sativa L.), an important self-pollinating annual forage legume.
      However, pod shattering is one of the most important defects that limits the
      reproduction of the vetch in the field and the usage as a leguminous forage crop.
      To better understand the vetch pod shattering mechanism, we used high-throughput
      RNA sequencing to assess the global changes in the transcriptomes of the pod
      ventral sutures of shattering-susceptible and shattering-resistant vetch
      accessions screened from 541 vetch germplasms. A total of 1,285 significantly
      differentially expressed unigenes (DEGs) were detected, including 575 up
      regulated unigenes and 710 down-regulated unigenes. Analyses of Gene Ontology and
      KEGG metabolic enrichment pathways of 1,285 DEGs indicated that 22 DEGs encoding
      cell wall modifications and hydrolases associated with pod shattering were highly
      expressed in shattering-susceptible accessions. These genes were mainly enriched
      in "hydrolase activity," "cytoplasm," and "carbohydrate metabolic process"
      systems. These cell wall modifications and hydrolases genes included beta
      glucosidase and endo-polygalacturonase, which work together to break down the
      glycosidic bonds of pectin and cellulose, and to promote the dissolution and
      disappearance of the cell wall in the ventral suture of the pod and make the pod
      more susceptible to shattering. We demonstrated the differences in gene
      transcription levels between the shattering-susceptible and shattering-resistant
      vetch accessions for the first time and our results provided valuable information
      for the identifying and characterizing of pod shattering regulation networks in
      vetch. This information may facilitate the future identification of pod
      shattering-related genes and their underlying molecular mechanisms in the common
      vetch.

PMID- 28496451
TI  - Genome-Wide Identification of Histone Modifiers and Their Expression Patterns
      during Fruit Abscission in Litchi.
AB  - Modifications to histones, including acetylation and methylation processes, play
      crucial roles in the regulation of gene expression in plant development as well
      as in stress responses. However, limited information on the enzymes catalyzing
      histone acetylation and methylation in non-model plants is currently available.
      In this study, several histone modifier (HM) types, including six histone
      acetyltransferases (HATs), 11 histone deacetylases (HDACs), 48 histone
      methyltransferases (HMTs), and 22 histone demethylases (HDMs), are identified in
      litchi (Litchi chinensis Sonn. cv. Feizixiao) based on similarities in their
      sequences to homologs in Arabidopsis (A. thaliana), tomato (Solanum
      lycopersicum), and rice (Oryza sativa). Phylogenetic analyses reveal that HM
      enzymes can be grouped into four HAT, two HDAC, two HMT, and two HDM subfamilies,
      respectively, while further expression profile analyses demonstrate that 17 HMs
      were significantly altered during fruit abscission in two field treatments.
      Analyses reveal that these genes exhibit four distinct patterns of expression in
      response to fruit abscission, while an in vitro assay was used to confirm the
      HDAC activity of LcHDA2, LcHDA6, and LcSRT2. Our findings are the first in-depth
      analysis of HMs in the litchi genome, and imply that some are likely to play
      important roles in fruit abscission in this commercially important plant.

PMID- 28496453
TI  - Grapevine Grafting: Scion Transcript Profiling and Defense-Related Metabolites
      Induced by Rootstocks.
AB  - Rootstocks are among the main factors that influence grape development as well as
      fruit and wine composition. In this work, rootstock/scion interactions were
      studied using transcriptomic and metabolic approaches on leaves of the
      "Gaglioppo" variety, grafted onto 13 different rootstocks growing in the same
      vineyard. The whole leaf transcriptome of "Gaglioppo" grafted onto five selected
      rootstocks showed high variability in gene expression. In particular, significant
      modulation of transcripts linked to primary and secondary metabolism was
      observed. Interestingly, genes and metabolites involved in defense responses
      (e.g., stilbenes and defense genes) were strongly activated particularly in the
      GAG-41B combination, characterized in addition by the down-regulation of abscisic
      acid (ABA) metabolism. On the contrary, the leaves of "Gaglioppo" grafted onto
      1103 Paulsen showed an opposite regulations of those transcripts and metabolites,
      together with the greater sensitivity to downy mildew in a preliminary in vitro
      assay. This study carried out an extensive transcriptomic analysis of rootstock
      effects on scion leaves, helping to unravel this complex interaction, and
      suggesting an interesting correlation among constitutive stilbenes, ABA compound,
      and disease susceptibility to a fungal pathogen.

PMID- 28496454
TI  - Expression Analyses of Embryogenesis-Associated Genes during Somatic
      Embryogenesis of Adiantum capillus-veneris L. In vitro: New Insights into the
      Evolution of Reproductive Organs in Land Plants.
AB  - An efficient in vitro regeneration system via somatic embryogenesis (SE) was
      developed for a fern species Adiantum capillus-veneris. Adventitious shoots,
      green globular bodies (GGBs) and calli were obtained with the maximal induction
      rate on the Murashige and Skoog (MS) medium of low concentrations of 6
      benzyladenine (BA) (0-1.0 mg/L), 2.0 mg/L BA without 2,4-dichlorophenoxyacetic
      acid (2,4-D), 0.5 mg/L 2,4-D and 0.5-1.0 mg/L 6-BA, respectively. Cyto
      morphological and histological changes in the shoot development via calli and
      GGBs were examined. For a better understanding of these developmental events,
      expression patterns of six genes, AcLBD16, AcAGL, AcBBM, AcWUS, AcRKD, and
      AcLEC1, were characterized during SE. AcBBM and AcLEC1 were ubiquitously
      expressed in direct SE (adventitious shoots and GGBs) the maximal expression of
      AcBBM in mature GGBs, and the high expression of AcLEC1 in GGB initiation and
      adventitious shoots. During the indirect SE, AcLBD16, AcLEC1, AcRKD, and AcWUS
      were highly expressed in mature calli. Additionally, phylogenetic analyses showed
      that AcWUS, AcBBM, AcLBD, AcAGL, AcRKD, and their homologs of other green plants
      formed monophyletic clades, respectively. Some of these gene families, however,
      diversified rapidly with the occurrence of embryophytes, suggesting that
      embryogenesis-associated genes could experience a rapid evolution with the
      colonization of plants to terrestrial environments. Expression and phylogenetic
      analyses of those embryogenesis-associated genes by the aid of in vitro
      regeneration system of A. capillus-veneris provide new insights into the
      evolution of reproductive organs in land plants.

PMID- 28496455
TI  - Comparative Proteomic Analysis of the Graft Unions in Hickory (Carya cathayensis)
      Provides Insights into Response Mechanisms to Grafting Process.
AB  - Hickory (Carya cathayensis), a tree with high nutritional and economic value, is
      widely cultivated in China. Grafting greatly reduces the juvenile phase length
      and makes the large scale cultivation of hickory possible. To reveal the response
      mechanisms of this species to grafting, we employed a proteomics-based approach
      to identify differentially expressed proteins in the graft unions during the
      grafting process. Our study identified 3723 proteins, of which 2518 were
      quantified. A total of 710 differentially expressed proteins (DEPs) were
      quantified and these were involved in various molecular functional and biological
      processes. Among these DEPs, 341 were up-regulated and 369 were down-regulated at
      7 days after grafting compared with the control. Four auxin-related proteins were
      down-regulated, which was in agreement with the transcription levels of their
      encoding genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis
      showed that the 'Flavonoid biosynthesis' pathway and 'starch and sucrose
      metabolism' were both significantly up-regulated. Interestingly, five flavonoid
      biosynthesis-related proteins, a flavanone 3-hyfroxylase, a cinnamate 4
      hydroxylase, a dihydroflavonol-4-reductase, a chalcone synthase, and a chalcone
      isomerase, were significantly up-regulated. Further experiments verified a
      significant increase in the total flavonoid contents in scions, which suggests
      that graft union formation may activate flavonoid biosynthesis to increase the
      content of a series of downstream secondary metabolites. This comprehensive
      analysis provides fundamental information on the candidate proteins and secondary
      metabolism pathways involved in the grafting process for hickory.

PMID- 28496456
TI  - Swallowing Disorders after Oral Cavity and Pharyngolaryngeal Surgery and Role of
      Imaging.
AB  - Head and neck squamous cell carcinoma is the sixth most common cancer diagnosed
      worldwide and the eighth most common cause of cancer death. Malignant tumors of
      the oral cavity, oropharynx, and larynx can be treated by surgical resection or
      radiotheraphy with or without chemotheraphy and have a profound impact on quality
      of life functions, including swallowing. When surgery is the chosen treatment
      modality, the patient may experience swallowing impairment in the oral and
      pharyngeal phases of deglutition. A videofluoroscopic study of swallow enables
      the morphodynamics of the pharyngeal-esophageal tract to be accurately examined
      in patients with prior surgery. These features allow an accurate tracking of the
      various phases of swallowing in real time, identifying the presence of functional
      disorders and of complications during the short- and long-term postoperative
      recovery. The role of imaging is fundamental for the therapist to plan
      rehabilitation. In this paper, the authors aim to describe the videofluoroscopic
      study of swallow protocol and related swallowing impairment findings in
      consideration of different types of surgery.

PMID- 28496457
TI  - Trends in Iran Pharmaceutical Market.

PMID- 28496458
TI  - Preparation, Optimization and Toxicity Evaluation of (SPION-PLGA) +/-PEG
      Nanoparticles Loaded with Gemcitabine as a Multifunctional Nanoparticle for
      Therapeutic and Diagnostic Applications.
AB  - The aim of this study was to develop a novel multifunctional nanoparticle, which
      encapsulates SPION and Gemcitabine in PLGA +/- PEG to form multifunctional drug
      delivery system. For this aim, super paramagnetic iron oxide nanoparticles
      (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem)
      in PLGA +/- PEG copolymers via W/O/W double emulsification method. Optimum size
      and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic
      applications were considered and the preparation parameters systematically were
      investigated and physicochemical characteristics of optimized nanoparticle were
      studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same
      optimized parameters and the toxicity of these nanoparticles was compared with
      Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation
      parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to
      0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all
      nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between
      13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine
      release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and
      SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine
      were 1.53 and 1.89 respectively. The statistical difference was significant (p
      value = 0.006 for SPION-PLGA-Gem and p-value = 0.015 for PLGA-Gem compared with
      Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded
      super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future
      work includes in-vitro and in-vivo investigation of radiosensitization and other
      application of these nanoparticles.

PMID- 28496459
TI  - Fabrication and in-vitro Evaluation of Ketotifen Fumarate-loaded PLGA
      Nanoparticles as a Sustained Delivery System.
AB  - Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the
      effects of certain endogenous substances known to be inflammatory mediators, and
      thereby exerts antiallergic activity. The present study describes the formulation
      of a sustained release nanoparticle (NP) drug delivery system containing
      ketoftifen, using poly (D,L lactide-co-glycolide) acid (PLGA). Biodegradable NPs
      were prepared using 50 : 50 PLGA by a water in-oil-in-water (w/o/w) double
      emulsion-solvent evaporation procedure and characterized for drug content, DSC
      (differential scanning calorimetry, XRD (X-ray diffractionl), FTIR (Fourier
      transform spectroscopy), particle size , surface morphology using scanning
      electron microscopy, and drug release rate. The effects of different drug-to
      polymer ratios on the characteristics of the NPs were investigated. NPs prepared
      were spherical with a smooth surface. Size of NPs was dependent on the
      concentration of polymer (10 mg/mL, 754.6 nm). Increasing the external organic
      phase volume (primary emulsion) resulted in larger particles with higher
      encapsulation efficiency (55%). The best drug to polymer ratio in the NP was F3
      (1:10 ratio) which showed loading efficiency of 55%, and mean particle size of
      754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical
      interaction between the drug and PLGA. The NPs prepared with low ratio of drug to
      polymer (1:5) F1 formulation showed faster dissolution rate than those with high
      drug to polymer ratio (1:10) F3 formulation. In conclusion, by selecting an
      appropriate level of the investigated parameters, spherical NPs with
      encapsulation efficiencies higher than 55% and a prolonged drug release over 24h
      (73.67-90.05%) were obtained.

PMID- 28496460
TI  - Doxorubicin Loaded DNA Aptamer Linked Myristilated Chitosan Nanogel for Targeted
      Drug Delivery to Prostate Cancer.
AB  - Recently, specific attention has been paid to aptamers, short DNA or RNA, as a
      tool for cancer diagnosis and therapy. In the present study MCS nanogels were
      prepared by Myristate: Chitosan at 1:9 ratio and were characterized by several
      techniques. A selected ssDNA aptamer (Apt) capable of detecting LNCaP cells was
      linked to Myristilated Chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded
      with Doxorubicin (DOX) to be used in targeted drug delivery against the Prostate
      cancer cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the
      binding efficiency was estimated by flow cytometry. The binding affinity of the
      selected aptamers was above 70% compared to the initial library. The loading
      capacity of the nanogel was as high as 97% and up to 40% of DOX were released
      from MCS within 15 days. Cytotoxicity of nanodrug on LNCaP cells was determined
      by MTT assay. Apt-MCS-DOX was specifically binded to LNCaP cells whereas it
      didn't show any specificity to PC-3 cells as a negative control. Both MCS-DOX and
      Apt-MCS-DOX showed a lethal effect on LNCaP cells. Our results can lead to an
      aptamer based simple and applicable technique for early diagnosis and treatment
      of cancerous cells.

PMID- 28496461
TI  - Simultaneous Optimization of Multiple Response Variables for the Gelatin-chitosan
      Microcapsules Containing Angelica Essential Oil.
AB  - Angelica essential oil (AO), a major pharmacologically active component of
      Angelica sinensis (Oliv.) Diels, possesses hemogenesis, analgesic activities, and
      sedative effect. The application of AO in pharmaceutical systems had been limited
      because of its low oxidative stability. The AO-loaded gelatin-chitosan
      microcapsules with prevention from oxidation were developed and optimized using
      response surface methodology. The effects of formulation variables (pH at complex
      coacervation, gelatin concentration, and core/wall ratio) on multiple response
      variables (yield, encapsulation efficiency, antioxidation rate, percent of drug
      released in 1 h, and time to 85% drug release) were systemically investigated. A
      desirability function that combined these five response variables was
      constructed. All response variables investigated were found to be highly
      dependent on the formulation variables, with strong interactions observed between
      the formulation variables. It was found that optimum overall desirability of AO
      microcapsules could be obtained at pH 6.20, gelatin concentration 25.00%, and
      core/wall ratio 40.40%. The experimental values of the response variables highly
      agreed with the predicted values. The antioxidation rate of optimum formulation
      was approximately 8 times higher than that of AO. The in-vitro drug release from
      microcapsules was followed Higuchi model with super case-II transport mechanism.

PMID- 28496462
TI  - Synthesis and Characterization of Biodegradable Semi-Interpenetrating Polymer
      Networks Based on Star-Shaped Copolymers of E-Caprolactone and Lactide.
AB  - In this paper, the focus is on a new kind of biodegradable semi-interpenetrating
      polymer networks, which is derived from E-caprolactone, lactide, 1,4-butane
      diisocyanate and ethylenediamine and also its potential has been investigated in
      soft tissue engineering applications. The polymers were characterized by nuclear
      magnetic resonance (NMR) spectrometry, Fourier transform infrared spectroscopy
      (FT-IR), differential thermal analysis (DTA), differential scanning calorimetry
      (DSC), and thermogravimetric analysis (TGA). These experiments show that the
      polymers with the right composition and the expected molecular weight were
      achieved. Also, the in-vitro degradation of polymer network was examined in
      phosphate buffer solutions (pH 7.4) at 37  degrees C. Moreover, cell viability
      and adhesion tests were carried out with fibroblast cells by the MTT assay, which
      confirmed biocompatibility. Polyurethane materials have superior mechanical
      properties, so these biodegradable and biocompatible films demonstrate potential
      for future application as cell scaffolds in soft tissue engineering applications.

PMID- 28496463
TI  - Antibacterial Loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder
      Aerosol for the Treatment of Lung Infections.
AB  - Inhalation delivery of aerosolized antibacterials is preferred over conventional
      methods of delivery for targeting lung infection. The present study is concerned
      with the development and characterization of a novel, spray dried, aerosolized,
      chitosan polyelectrolyte complex (PEC) based microparticles containing
      antibacterials for the treatment of lung infections. Chitosan polyelectrolyte
      complex microparticles were formulated by spray drying process. Prepared spray
      dried chitosan PEC microparticles were studied for surface morphology, drug
      encapsulation efficiency, moisture content, Carr's index, solid state interaction
      by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity
      studies of microparticles were carried out on H1299 alveolar cell lines.
      Antibacterial efficacy of microparticles was assessed on the basis of
      determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of
      rats using PK/PD analysis. The PEC microparticles were mostly spherical and
      exhibited high drug encapsulation efficiency. Release profiles showed an initial
      burst phase followed by a secondary sustained release phase. Good aerosolization
      behaviour as dry powder inhaler was demonstrated by microparticles with high
      values of recovered dose, emitted dose, and fine particle fraction. No overt
      cytotoxicity of microparticles was detected against H1299 alveolar cell line.
      More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with
      microparticles as compared to intravenously administered antibacterial solution.
      The findings of the study suggest that chitosan polyelectrolyte complex based
      microparticles as dry powder inhaler can be an efficient antibacterial delivery
      system for sustained and effective management of lung infection.

PMID- 28496464
TI  - Using beta-cyclodextrin and Arabic Gum as Wall Materials for Encapsulation of
      Saffron Essential Oil.
AB  - Saffron essential oil has a pleasant aroma and medicinal activities. However, it
      is sensible into the environmental condition. Therefore, it should be protected
      against unwanted changes during storage or processing. Encapsulation is
      introduced as a process by which liable materials are protected from unwanted
      changes. In the present study, different ratios (0:100, 25:75, 50:50, 75:25, and
      100:0) of beta-cyclodextrin (beta-CD) and arabic gum (GA) were used as wall
      martial for encapsulation saffron essential oil. In order to calculate of loading
      capacity (LC) and encapsulation efficiency (EE), and release (RE), safranal was
      determined as indicator of saffron essential oil using GC. According to the
      results, the highest LC and EE were related to the mixture of beta-CD/GA at a
      75:25 ratio. In contrast, the lowest encapsulate hygroscopicity (EH) and RE were
      observed when only beta-CD was applied as wall material (P<=0.05). Comparing the
      differential scanning calorimetry (DSC) thermograms of the control and
      encapsulate of beta-CD/GA (75:25) confirmed encapsulation of saffron essential
      oil. Scanning electron microscopy (SEM) images with high magnifications showed
      the rhombic structure that partially coated by GA. The mixture of beta-CD/GA at a
      75:25 ratio can be recommended for saffron essential oil encapsulation.

PMID- 28496465
TI  - Effect of Nonionic Surfactants (Dodecyl Maltoside and Polysorbate 20) on
      Prevention of Aggregation and Conformational Changes of Recombinant Human
      IFNbeta_1b Induced by Light.
AB  - Liquid protein formulations are prone to form aggregates. The effect of nonionic
      surfactants such as Polysorbate 20 (PS 20) and n-Dodecyl beta-D-maltoside (DDM)
      on the prevention of aggregation and conformational changes of recombinant human
      IFNbeta-1b (rhIFN beta_1b) was explored. Polysorbate has been used in
      formulations of protein pharmaceuticals. There have been concerns about using PS
      20 due to its residual peroxide content which may negatively affect protein
      efficacy. n-Dodecyl beta-D-maltoside has been of interest and shown to be highly
      effective in prevention of aggregation. Fresh bulk of rhIFN beta_1b was
      formulated using DDM or different concentrations of PS 20. Formulations were
      exposed to light stress condition according to the ICH guideline of Q1b. The
      overall conformational integrity of individual samples was characterized by a
      combination of Circular dichroism (CD), Fluorescence spectroscopy and RP_HPLC
      techniques. The CD spectrum depicting the conformational integrity of rhIFN
      beta_1b showed 31.9% and 31.2% decreases in alpha-helix content of protein
      samples with 0.2% or 0.02% of PS20 compared to only18.2% of that containing 0.2%
      DDM. The RP-HPLC analysis also showed that the oxidized impurity in formulation
      containing DDM is less than those contain PS 20. Complementary analysis of the
      liquid formulations using IFR and UV methods also was in compliance with the data
      obtained by CD. Compared to PS 20, the sample of rhIFN beta_1b formulation with
      DDM was more resistant to the destruction effect of light. Results were in
      accordance with previous studies and could suggest DDM as a reliable anti
      aggregation surfactant in biopharmaceutical formulations.

PMID- 28496466
TI  - Validated Spectrophtometric Method for Simultaneous Determination of
      Buprenorphine and Naloxone in Pharmaceutical Dosage Forms.
AB  - Buprenorphine is a partial mu agonist and kappa antagonist which is used for the
      treatment of pain and opioid addiction. A mixture of buprenorphine hydrochloride
      and naloxone hydrochloride has been approved for the treatment of opioid
      dependence. In this study a third order derivative spectrophotometric method
      based on zero-crossing technique has been used for the simultaneous determination
      of buprenorphine hydrochloride and naloxone hydrochloride in tablets. The
      measurements were carried out at wavelengths of 257.8 (zero-crossing point of
      naloxone hydrochloride) and 252.2 nm (zero-crossing point of buprenorphice
      hydrochloride) for buprenorphine hydrochloride and naloxone hydrochloride,
      respectively in the third order derivative spectra obtained in methanol and 0.1 M
      NaOH (50:50) as solvent. The method was found to be linear in the range of 20-80
      ug/mL for buprenorphine hydrochloride and 5-20 ug/mL for naloxone hydrochloride.
      The within-day and between-day coefficient of variation and error values were
      less than 2.5% and 1.8%, respectively. The proposed method was successfully used
      for simultaneous determination of these drugs in pharmaceutical dosage form
      without any interference from excipients or need to prior separation before
      analysis.

PMID- 28496467
TI  - Interference-free Determination of Carbamazepine in Human Serum Using High
      Performance Liquid Chromatography: A Comprehensive Research with Three-way
      Calibration Methods.
AB  - In the present study, a comprehensive and systematic strategy was described to
      evaluate the performance of several three-way calibration methods on a bio
      analytical problem. Parallel factor analysis (PARAFAC), alternating trilinear
      decomposition (ATLD), self-weighted alternating trilinear decomposition (SWATLD),
      alternating penalty trilinear decomposition (APTLD), and unfolded partial least
      squares combined with the residual bilinearization procedure (U-PLS/RBL) were
      applied on high performance liquid chromatography with photodiode-array detection
      (HPLC-DAD) data to quantify carbamazepine (CBZ) in different serum samples. Using
      the proposed approach, successfully quantification of CBZ in human plasma, even
      in the presence of diverse uncalibrated serious interfering components was
      achieved. Moreover, the accuracy and precision of each algorithm for analyzing
      CBZ in serum samples were compared using root mean square error of prediction
      (RMSEP), the recovery values and figures of merits and reproducibility of the
      analysis. Satisfying recovery values for the analyte of interest were obtained by
      HPLC-DAD on a Bonus-RP column using an isocratic mode of elution with
      acetonitrile/K2HPO4 (pH = 7.5) buffer solution (45:55) coupled with second-order
      calibrations. Decreas of the analysis time and less solvent consumption are some
      of the pluses of this method. The analysis of real samples showed that the
      modeling of complex chromatographic profiles containing CBZ as the target drug
      using any of the mentioned algorithms can be potentially benefit drug monitoring
      in therapeutic research.

PMID- 28496468
TI  - A Simple and Specific Stability- Indicating RP-HPLC Method for Routine Assay of
      Adefovir Dipivoxil in Bulk and Tablet Dosage Form.
AB  - A simple and reliable stability-indicating RP-HPLC method was developed and
      validated for analysis of adefovir dipivoxil (ADV).The chromatographic separation
      was performed on a C18 column using a mixture of acetonitrile-citrate buffer (10
      mM at pH 5.2) 36:64 (%v/v) as mobile phase, at a flow rate of 1.5 mL/min.
      Detection was carried out at 260 nm and a sharp peak was obtained for ADV at a
      retention time of 5.8 +/- 0.01 min. No interferences were observed from its
      stress degradation products. The method was validated according to the
      international guidelines. Linear regression analysis of data for the calibration
      plot showed a linear relationship between peak area and concentration over the
      range of 0.5-16 MUg/mL; the regression coefficient was 0.9999and the linear
      regression equation was y = 24844x-2941.3. The detection (LOD) and quantification
      (LOQ) limits were 0.12 and 0.35 MUg/mL, respectively. The results proved the
      method was fast (analysis time less than 7 min), precise, reproducible, and
      accurate for analysis of ADV over a wide range of concentration. The proposed
      specific method was used for routine quantification of ADV in pharmaceutical bulk
      and a tablet dosage form.

PMID- 28496469
TI  - Development of an Analytical Method for Dibutyl Phthalate Determination Using
      Surrogate Analyte Approach.
AB  - Dibutyl phthalate (DBP) is a phthalic acid ester and is widely used in polymeric
      products to make them more flexible. DBP is found in almost every plastic
      material and is believed to be persistent in the environment. Various analytical
      methods have been used to measure DBP in different matrices. Considering the
      ubiquitous nature of DBP, the most important challenge in DBP analyses is the
      contamination of even analytical grade organic solvents with this compound and
      lack of availability of a true blank matrix to construct the calibration line.
      Standard addition method or using artificial matrices reduce the precision and
      accuracy of the results. In this study a surrogate analyte approach that is based
      on using deuterium labeled analyte (DBP-d4) to construct the calibration line was
      applied to determine DBP in hexane samples.

PMID- 28496470
TI  - QSAR Studying of Oxidation Behavior of Benzoxazines as an Important
      Pharmaceutical Property.
AB  - In this work the electrooxidation half-wave potentials of some Benzoxazines were
      predicted from their structural molecular descriptors by using quantitative
      structure-property relationship (QSAR) approaches. The dataset consist the half
      wave potential of 40 benzoxazine derivatives which were obtained by DC
      polarography. Descriptors which were selected by stepwise multiple selection
      procedure are: HOMO energy, partial positive surface area, maximum valency of
      carbon atom, relative number of hydrogen atoms and maximum electrophilic reaction
      index for nitrogen atom. These descriptors were used for development of multiple
      linear regression (MLR) and artificial neural network (ANN) models. The
      statistical parameters of MLR model are standard errors of 0.016 and 0.018 for
      training and test sets, respectively. Also, these values are 0.012 and 0.017 for
      training and test sets of ANN model, respectively. The predictive power of these
      models was further examined by leave-eight-out cross validation procedure. The
      obtained statistical parameters are Q2 = 0.920 and SPRESS = 0.020 for MLR model
      and Q2 = 0.949 and SPRESS = 0.015 for ANN model, which reveals the superiority of
      ANN over MLR model. Moreover, the results of sensitivity analysis on ANN model
      indicate that the order of importance of descriptors is: Relative number of H
      atom > HOMO energy > Maximum electrophyl reaction index for N atom > Partial
      positive surface area (order-3) > maximum valency of C atom.

PMID- 28496471
TI  - Ionic Liquid-assisted Synthesis of Celexocib Using Tris-(2-hydroxyethyl) Ammonium
      Acetate as an Efficient and Reusable Catalyst.
AB  - Celecoxib is classified as none traditional nonsteroidal anti-inflammatory drugs
      (NSAIDs). This compound has conventional properties of NSAIDs such as anti
      inflammatory, analgesic, and antipyretic activities beside reduced risk of
      gastrointestinal side effect of traditional NSAIDs such as ibuprofen. This
      compound gets a second sale rank of NSAIDs market at 2016 in the world and sales
      more than 17000 Kg in Iran during the past 6 month. So, a simple, rapid and green
      method for synthesis of this compound is important. In the present study, a novel
      green method was suggested for the synthesis of celecoxib using the ionic liquid.
      Celecoxib was provided by the reaction of trifluoroacetone, 4
      methylbenzoylchloride, and 4-hydrazinobenzenesulfonamide hydrochloride. The tris
      (2-hydroxyethyl) ammonium acetate as ionic liquid was prepared by mixing tris-(2
      hydroxyethyl) ammonium and acetic acid, and used as an efficient catalyst. The
      structure of the synthetic products was confirmed by analytical and spectroscopic
      methods including 1HNMR, 13CNMR, IR, MS and elemental analysis. This ionic liquid
      can play dual roles in the synthesis of celecoxib, as a catalyst to improve
      electrophilicity of carbonyl group and also as a solvent of reaction. The
      reaction rate and yield (86%) were improved considerably. Moreover IL showed the
      same efficiency when used in 4 consecutive reactions.

PMID- 28496472
TI  - Synthesis and Biological Evaluation of N-(5-(pyridin-2-yl)-1,3,4-thiadiazol-2
      yl)benzamide Derivatives as Lipoxygenase Inhibitor with Potential Anticancer
      Activity.
AB  - In the recent years, the role of LOX enzymes in the origin of neoplastic diseases
      such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new
      series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized
      and the cytotoxicity of the members of this series was assessed using MTT
      protocol. Enzyme inhibitory activity of the prepared compounds was also tested
      against 15-lipoxygenase-1 as a novel target for the discovery of anticancer
      drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were
      compared with doxorubicin. Overall, nitro containing derivatives exerted a higher
      cytotoxic activity against PC3 cell line and methoxylated derivatives showed an
      acceptable activity against SKNMC cell line. Methoxylated derivatives were also
      the most potent enzyme inhibitors especially at position ortho of the phenyl
      residue.

PMID- 28496473
TI  - Molecular Dynamics and Docking Investigations of Several Zoanthamine-Type Marine
      Alkaloids as Matrix Metaloproteinase-1 Inhibitors.
AB  - Zoanthamine-type alkaloids display a wide spectrum of biological effects. This
      study aimed to examine the inhibitory effects of norzoanthamine and its ten
      homologues of zoanthamine class on human fibroblast collagenase by modeling a
      three-dimensional structure of the ligands at collagenase using energy
      minimization, docking, molecular dynamics simulation and MM-PB/GBSA binding free
      energy calculations. The results showed that zoanthamide, zooxathellamine and
      enol-iminium form of norzoanthamine, with lower binding free energies than other
      compounds, are potent inhibitors of collagenase. However, the enol-iminium form
      of norzoanthamine showed a more inhibitory activity against collagenase than its
      keto form. This suggests that it can be used for treatment of many diseases such
      as osteoporosis, autoimmune diseases, and cancer. Zinc-binding residues such as
      His 118, His 122 and His 128 for hydrogen bonds and Leu 81, Tyr 110, Val 115, Leu
      126, Pro 138, Ser 139 for hydrophobic interactions should be considered for
      designing an inhibitor for collagenase. Our theoretical results and MM/GBSA
      binding free energy calculations are consistent with experimental studies.

PMID- 28496474
TI  - Enhancement of Antinociceptive Effect by Co-administration of Amitriptyline and
      Crocus Sativus in a Rat Model of Neuropathic Pain.
AB  - The aim of this study was to evaluate the anti-nociceptive effects of a low, sub
      effective dose of amitriptyline, in combination with the different doses of
      ethanolic and aqueous extracts of Crocus sativus following sciatic nerve chronic
      constriction injury (CCI) in rats. Amitriptyline (3, 10 and 30 mg/Kg, i.p.) and
      the extracts (25, 50 and 100 mg/Kg, i.p.), were separately administered at the
      time of CCI for 7 consecutive days. In combination therapy, the sub
      antinociceptive dose of amitriptyline (3 mg/Kg) was given with the three
      different doses of extracts for seven days. Mechanical allodynia, thermal
      allodynia and thermal hyperalgesia were evaluated by von Frey, acetone and
      radiant heat tests, respectively, 1 day before and on days 3, 5 and 7 after
      surgery. Co-administration of amitriptyline (3 mg/Kg) with aqueous extract (50,
      100 mg/Kg,) produced more potent cold anti-allodynic (P < 0.01 and P < 0.001,
      respectively) as well as thermal anti-hyperalgesic (P < 0.05) effects than that
      produced by each of them. Amitriptyline (3 mg/Kg) plus ethanolic extract (50, 100
      mg/Kg) produced more potent cold anti-allodynic (P < 0.05 and P < 0.001,
      respectively) as well as thermal anti-hyperalgesic (P < 0.05) effects as compared
      with the sum effects produced by each of them. Mechanical anti-allodynia effect
      was only potentiated with the co-administration of amitriptyline with the high
      dose of aqueous extract (100 mg/Kg, P < 0.001). Our study supports the use of
      saffron as an adjunctive to amitriptyline to improve the therapeutic outcome in
      the management of neuropathic pain.

PMID- 28496475
TI  - The Effect of Green Tea Extract on Oxidative Stress and Spatial Learning in
      Streptozotocin-diabetic Rats.
AB  - : Diabetes mellitus is associated with distribution of cognitive functioning.
      Hyperglycemia induced oxidative stress has been proposed as a cause of memory
      complications of diabetes including cognitive impairment. The aim of this study
      was to examine total green tea extract (TGTE), a potent free radical scavenger
      against spatial impairment in Streptozotocin-diabetic rats. Eight weeks after
      diabetes induction, TGTE was administrated throught drinking water 3 mg/L. The
      learning and memory behavior was evaluated with Morris water maze task in male
      rats. Then, for estimation of oxidative stress parameters such as lipid
      peroxidation (LPO), total antioxidant capacity (FRAP) and total thiol groups in
      blood were measured. The total green tea extract showed improved cognitive
      impairment in diabetic groups but these changes weren't significant. There was
      also significant increase FRAP level and total thiol groups in treated green tea
      groups vs. CONTROL: group. This study demonstrated the effectiveness of TGTE on
      spatial impairment and oxidative stress induced in diabetes mellitus.

PMID- 28496476
TI  - In-vitro Antioxidant, Cytotoxic, Cholinesterase Inhibitory Activities and Anti
      Genotoxic Effects of Hypericum retusum Aucher Flowers, Fruits and Seeds Methanol
      Extracts in Human Mononuclear Leukocytes.
AB  - The present study investigates the antioxidant, anticancer, anticholinesterase,
      anti-genotoxic activities and phenolic contents of flower, fruit and seed
      methanol extracts of Hypericum retusum AUCHER. The amounts of protocatechuic
      acid, catechin, caffeic acid and syringic acid in methanol extracts were
      determined by HPLC. Total phenolic content of H. retusum seed extract was found
      more than fruit and flower extracts. The DPPH free radical scavenging activity of
      flower and seed methanol extracts showed close activity versus BHT as control.
      Among three extracts of H. retusum only flower methanol extract was exhibited
      considerable cytotoxic activities against to HeLa and NRK-52E cell lines.
      Moreover, seed methanol extract showed both acetyl and butyrl-cholinesterase
      inhibitory activity. The highest anti-genotoxic effects were seen 25 and 50
      MUg/mL concentrations. In this study, the extracts showed a strong antioxidant
      and anti-genotoxic effect. The seed extract was more efficient- than extracts of
      fruit and flowers. Our results suggest that the antioxidant and anti-genotoxic
      effects of extracts depend on their phenolic contents. Further studies should
      evaluate the in-vitro and in-vivo the benefits of H. retusum seed methanol
      extracts.

PMID- 28496477
TI  - Cytotoxic Properties of Three Isolated Coumarin-hemiterpene Ether Derivatives
      from Artemisia armeniaca Lam.
AB  - Considering multiple reports on cytotoxic activity of the Artemisia genus and its
      phytochemicals, in the current study A. armeniaca Lam. and the three components
      isolated from the plant were subjected to cytotoxic studies. Analytical
      fractionation of A. armeniaca aerial parts for the first time was directed to the
      isolation of 7-hydroxy-8-(4-hydroxy-3-methylbutoxy) comarin (armenin), 8-hydroxy
      7-(4-hydroxy-3-methylbutoxy) comarin (isoarmenin) and deoxylacarol. Cytotoxicity
      assessed with alamalBlue(r) assay and apoptosis was detected by PI staining and
      western blot analysis of Bax and PARP proteins. Extracts and all compounds
      exhibited cytotoxic activity against apoptosis-proficient HL-60 and apoptosis
      resistant K562 cells, with the lowest cytotoxic activity on J774 cell line as non
      malignant cell. Armenin as the most potent component decreased the viability of
      cell with IC50 of 22.5 and 71.1 uM for K562 and HL-60 cells respectively and
      selected for further mechanistic study. Armenin increased the sub-G1 peak in flow
      cytometry histogram of HL-60 and K562 treated cells and increase in the amount of
      Bax protein and the cleavage of PARP in comparison with the control after
      treatment for 48 h in K562 treated cells verified the apoptotic activity of the
      armenin. Taken together, according to the finding of this study armenin was
      introduced as a novel cytotoxic compound with apoptotic activity, which is
      encouraging for further mechanistic and clinical studies.

PMID- 28496478
TI  - Study of Crocin & Radiotherapy-induced Cytotoxicity and Apoptosis in the Head and
      Neck Cancer (HN-5) Cell Line.
AB  - Malignant tumors of head and neck carcinomas are the sixth most common type of
      cancer. Current systemic therapies for cancer show side effects in normal tissues
      and short-term efficacy due to drug resistance. Consequently, there is much
      interest in identifying new drugs for cancer treatment. Crocin (an active
      ingredient of saffron) has been shown to have cytotoxic effects on cancer cell
      lines. Chemo radiotherapy is the standard treatment for head and neck cancer. In
      the present study, the cytotoxic effects, inducing apoptosis and the radiation
      sensitivity of crocin were evaluated in the head and neck cancer cell line (HN
      5). HN-5 cells were cultured in a DMEM medium and incubated with different
      concentrations of crocin (12.5-1000 ug/mL). They were exposed to 2 Gy gamma-rays.
      Cell viability was quantified by the MTT assay. Apoptotic cells were determined
      using PI staining of DNA fragmentation by flowcytometry (sub-G1 peak). Crocin
      decreased cell viability in HN-5 cells in a time and concentration dependent
      manner. Crocin also induced a sub-G1 peak in the flowcytometery histogram of
      treated cells compared with the control, suggesting that apoptotic cell death is
      caused by its toxicity. Crocin was also shown to sensitize cells to radiation
      induced toxicity and apoptosis. The simultaneous use of crocin and radiation
      therefore increases radiation sensitivity and cell death. Thus, after further
      study crocin can be considered as a potential drug and sensitizer in cancer
      treatment.

PMID- 28496479
TI  - A Comparison of Hepatocyte Cytotoxic Mechanisms for Docetaxel and PLGA-Docetaxel
      Nanoparticls.
AB  - Docetaxel (DTX) is one of the most widely used drugs in oncology due to its high
      efficacy against several cancers. Though, its routine clinical administration,
      formulated in tween 80, causes serious side effects. Polylactide-co-glycolide
      (PLGA), biodegradable polyester synthesized and approved for human use, is
      employed to overcome these problems. In this investigation, we compare the
      cytotoxic mechanisms of DTX and PLGA-DTX in isolated rat hepatocytes.
      Cytotoxicity of DTX and PLGA-DTX were associated with reactive oxygen species
      formation, activation of caspases cascade, collapse of mitochondrial membrane
      potential (MMP), lysosomal membrane leakiness and ATP depletion. Our results also
      showed that CYP2E1 is involved in the oxidative stress cytotoxicity mechanism and
      both drugs are detoxified via phase II metabolic methylation. Furthermore, we
      concluded that PLGA-DTX is bioactivated by GSH. It could also potentiate
      hepatocyte toxicity through a mitochondrial/lysosomal toxic cross-talk. In
      addition to these observed differences, it is likely that mode of hepatocyte
      membrane penetration is different between these compounds.

PMID- 28496480
TI  - In-vitro Pro Apoptotic Effect of Crude Saponin from Ophiocoma erinaceus against
      Cervical Cancer.
AB  - Ophiocoma erinaceus Muller &Troschel (Ophiocomidae) is part of the extensive
      group of echinoderm that contains bioactive metabolites. As the anti cancer
      potential of brittle star saponin has not been reported against cervical cancer,
      the present study was conducted to evaluate the anticancer effect of extracted
      crude saponin. Saponin extraction was conducted using conventional method such as
      froth test, TLC, FTIR and erythrolysis assay. The Hela-S3 cervical carcinoma and
      HNCF-PI52 normal cells were treated with different concentrations of saponin
      fraction for 24 and 48 h. The cytotoxicity was examined by MTT, DAPI, AO/PI,
      Annexin V-FITC and flow cytometry. In addition, the apoptotic induced pathway was
      studied using caspase assay, evaluation of ROS generation and Bcl-2 mRNA level.
      Crude saponin showed cytotoxic properties in Hela-S3 cells (IC50of 23.4 ug/mL)
      without significant impact against normal cells. In addition, the crude saponin
      increased sub-G1 peak in flow cytometry histogram of treated cells, ROS
      generation and caspase-3 and -9 activity (IC50 of 11.10, 11.27 ug/mL). The dose
      dependent down regulation of Bcl-2 in treated cells demonstrated that saponin
      fraction can trigger intrinsic apoptotic pathway in cancer cells. This study
      provides valuable information about the apoptotic inducing effect of saponin
      fraction, which can offer new insights into the anticancer potential of saponin
      as a promising candidate against human cervical carcinoma.

PMID- 28496481
TI  - Evaluation of Various Biological Activities of the Aerial Parts of Scrophularia
      frigida Growing in Iran.
AB  - The current study was assigned to evaluate the total phenol, total flavonoid
      content (TPC, TFC) and antioxidant properties of extracts from the aerial parts
      of Scrophularia frigida (S. frigida). Extracts were also tested by preliminary
      phytochemical screening as well as cytotoxic activity against Artemia salina, MCF
      7 (human breast carcinoma) and SW-480 (colon carcinoma) and L-929 (normal) cell
      lines along with antimicrobial characteristic. DPPH, MTT and Brine shrimp
      lethality tests and disc diffusion method were carried out to determine the
      biological activities of the different extracts of S. frigida. In addition, the
      extracts which had more potent antioxidant and antiproliferative activity were
      further analyzed by NMR and GC-MS. 40% methanol-water (from MeOH extract)
      fraction showed higher amounts of TPC, TFC and antioxidant property. Findings of
      the study for general toxicity effect showed that dichloromethane (DCM) and MeOH
      extracts had weak to moderate effects. Furthermore, DCM extract indicated the
      most potent anti-proliferative activity against cancer cell lines. No evidence of
      antibacterial activity was determined. On the other hand, analysis of the potent
      extract DCM in cytotoxic assay showed the presence of trans-phytol and cis-oleic
      acid in GC-MS. Furthermore, NMR analysis of potent methanolic fractions in
      antioxidant tests revealed the presence of iridoids and phenolics. Generally, the
      results of TPC, TFC and antioxidant activity of extracts and fractions were in
      agreement with each other.

PMID- 28496482
TI  - Evaluation of the Synergistic Effect of Tomatidine with Several Antibiotics
      against Standard and Clinical Isolates of Staphylococcus aureus, Enterococcus
      faecalis, Pseudomonas aeruginosa and Escherichia coli.
AB  - Antibiotic resistance is an important problem in antibiotic treatment of
      infections, particularly in hospitals. Tomatidine is a plant secondary metabolite
      with antimicrobial and antifungal effects. This study examined the possible
      synergistic effect tomatidine with several antibiotics against standard and
      clinical strains of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas
      aeruginosa and Escherichia coli. After determining the minimum inhibitory
      concentrations (MICs) of antibiotics and tomatidine against the bacterial
      isolates using broth microdilution method, the synergistic effect between
      tomatidine and antibiotics was evaluated by checkerboard method and calculation
      of FIC indices. Tomatidine alone did not show any antimicrobial effect. However,
      it had synergistic effect with gentamicin and cefepime against standard and
      clinical isolates of S. aureus and P. aeruginosa, respectively. It also had
      synergistic effect with ampicillin and ciprofloxacin only against standard
      strains of E. faecalis and P. aeruginosa, respectively. In conclusion, tomatidine
      could be considered as a potential antibiotic potentiator for gentamicin,
      cefepime and ciprofloxacin, and ampicillin against Staphylococcus aureus,
      Pseudomonas aeruginosa, and Enterococcus faecalis infections, respectively.
      However, the toxicological and pharmacological properties of tomatidine for use
      as a therapeutic agent remain to be determined.

PMID- 28496483
TI  - Antibacterial Activity of Isolated Immunodominant Proteins of Naja Naja (Oxiana)
      Venom.
AB  - The aim of this study is to investigate antibacterial effects of immunodominant
      proteins isolated from the venom of Naja Naja Oxiana snake against Staphylococcus
      aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. The
      innate immune system is an important line of defense against bacterial diseases.
      Antibacterial peptides and proteins produced by snake venoms have recently
      attracted significant attention due to their relevance to bacterial diseases and
      the potential of being converted into new therapeutic agents. Identification of
      immunodominant proteins of the venom of Naja Naja Oxiana snake was performed by
      SDS-PAGE and western blot analysis. Identified proteins were isolated directly
      from preparative gel electrophoresis by Electro-elution. In the next step,
      antibacterial effects of immunodominant proteins were tested against several
      strains of clinical isolates, including S.aureus, B.subtilis (Gram-positive
      bacteria) P.aeruginosa and E.coli (Gram-negative bacteria) using broth
      microdilution and disc-diffusion assays. In order to compare the results of the
      disc-diffusion assay, antibacterial effects of several antibiotics (Gentamicin,
      Ampicillin, Penicillin, Amoxicillin and Ciprofloxacin) were also examined using
      the same conditions. Results showed that immunodominant proteins of (14, and
      65kDa) with high immunogenicity were very effective in inhibiting the growth of
      two Gram-positive bacteria (S.aureus, B.sub) that were tested. However, they were
      only moderately effective in inhibiting the growth of the two tested Gram
      negative bacteria (P.aeruginosa and E.coli). However, immunodominant proteins of
      22 kDa and 32kDa with high immunogenicity, showed slight effectiveness in
      inhibiting the growth of two; the Gram-positive and Gram-negative bacteria that
      were tested. To the best of our knowledge, these immunodominant proteins are
      novel antigens for potent antimicrobial effects against two gram-positive
      bacteria (S.aureus, B.subtilis ) and less antimicrobial effect against two gram
      negative bacteria (E.coli, P.aeruginosa) that were prepared .

PMID- 28496484
TI  - In-vitro Bioactivity and Phytochemical Screening of Extracts from Rhizomes of
      Eremostachys azerbaijanica rech. f. Growing in Iran.
AB  - The current study evaluated the general toxicity, antioxidant, antimicrobial, and
      cytotoxic activity of extracts obtained from the rhizomes of Eremostachys
      azerbaijanica (Labiatae) as well as analyzed the potent extracts using GC-MS.
      Extracts of E. azerbaijanica in n-hexane, dichloromethane (DCM) and methanol
      (MeOH) were prepared using a Soxhlet apparatus. The antioxidant activity of the
      extracts was evaluated for free radical scavenging activity by DPPH assay. The
      antimicrobial activity of samples was determined by disc diffusion and brine
      shrimp lethality assay (BSLA) was used to assess general toxicity. The
      cytotoxicity of each extract was determined by MTT assay against human colorectal
      adenocarcinoma (HT29), human lung carcinoma (A549) and a normal cell line (human
      umbilical vein endothelial cells, HUVEC). The MeOH extract showed significant
      antioxidant activity and the n-hexane and DCM extracts showed promising activity
      against gram-positive species when compared with amikacin as a standard.
      Moreover, the n-hexane extract displayed the most potent activity in general
      toxicity assay. The results showed that all three extracts have cytotoxic effects
      against the A549 cell line. In the case of HT29 cell lines, only the DCM extract
      exhibited cytotoxicity. Interestingly, none of the extracts showed significant
      cytotoxic activity against the HUVEC cell line. The bioassay-guided
      identification of constituents showed the presence of fatty acids and steroids as
      the compounds responsible for bioactivity in the non-polar extracts.

PMID- 28496485
TI  - Phytochemicals, Antioxidant and Antiproliferative Properties of Rosmarinus
      officinalis L on U937 and CaCo-2 Cells.
AB  - Rosmarinus officinalis L., a medicinal herb from the labiates family, has been
      reported to have potential benefit in the treatment and prevention of several
      diseases. In particular its phenolics have demonstrated protective effects on
      various types of cancer through several mechanisms. The present study aimed to
      determine the effects of rosemary phenolic extracts on human cell functions, with
      particular regard to their anti-proliferative properties in three cell types
      U937, CaCo-2 and the peripheral blood mononuclear cells (PBMCs). The radical
      scavenging and Ferric reducing abilities of the extracts have been assessed as
      well as their cyto-toxicity and effects on cell cycle distribution and apoptosis.
      About 13 compounds were identified with dominance of rosmarinic acid in the
      methanolic extract and phenolic diterpens in the ethyl acetate fraction
      (Carnosol, Carnosic acid and methyl Carnosate). The total polyphenolic content
      was important in the first extract with 2.589 +/- 0.005 g/100 g in gallic acid
      equivalent compared to 0.763 +/- 0.005 g/100 g. The methanolic fraction displayed
      higher antioxidant activity (DPPHIC50: 0.510 mg/mL and FRAP: 1.714 +/- 0.068 mmol
      Fe2+/g) while ethyl acetate showed pronounced antiproliferative effects (IC50:
      14.85 +/- 0.20ug/mL and 14.95 +/- 2.32 ug/mL respectively for U937 and CaCo-2
      cells). The anti-proliferative effect was associated with a cell cycle arrest in
      S phase for U937 (62% of the population at 5 ug/mL) with a concomitant decrease
      in G1 and G2/M phases. Tested extracts displayed in addition early apoptotic
      effects in U937 and late apoptosis in CaCo-2 cells. The obtained data indicate
      that the identified phenolics are at least partially responsible for the observed
      cytotoxicity.

PMID- 28496486
TI  - Chemical Composition and Antimicrobial Activities of Essential Oils of Some
      Coniferous Plants Cultivated in Egypt.
AB  - Family Cupressaceae is the largest coniferous plant family. Essential oils of
      many species belonging to family Cupressaceae are known to have several
      biological activities specially antimicrobial activity. The essential oils from
      aerial parts of Calocedrus decurrens Torr., Cupressus sempervirens stricta L. and
      Tetraclinis articulata (Vahl) Mast. were prepared by hydrodistillation. The
      chemical composition of the essential oils has been elucidated by gas
      chromatography-mass spectroscopy analysis. The prepared essential oils were
      examined against selected species of Gram-positive, Gram-negative bacteria and
      Candida species. Broth dilution methods were used to detect minimum inhibitory
      concentration (MIC), minimum bactericidal concentration (MBC) and minimum
      fungicidal concentration (MFC). Sixteen compounds were identified in the
      essential oils of both Calocedrus decurrens and Cupressus sempervirens L. and
      fifteen compounds were identified in the essential oil of Tetraclinis articulata.
      delta-3-Carene (43.10%), (+)-Cedrol (74.03%) and Camphor (21.23%) were the major
      constituents in the essential oils of Calocedrus decurrens, Cupressus
      sempervirens L. and Tetraclinis articulata, respectively. The essential oils
      showed strong antimicrobial activities against the selected microorganisms in
      concentration range 0.02 3- 3.03 uL/mL. This study could contribute to the
      chemotaxonomic characterization of family Cupressaceae. In addition, it proved
      that the essential oils under investigation possess potential antimicrobial
      properties.

PMID- 28496487
TI  - Chemical Composition and Biological Activities of Methanolic Extract of
      Scrophularia Oxysepala Boiss.
AB  - Isolated five known iridoids glycosides (Scrophuloside A, Harpagoside B, 5
      hydroxyloganin, 8-O-acetylharpagide and 6-O-methyl,1-glucopyranosyl catalpol),
      one phenyl ethanoid glycoside (Verbascoside) and a phenyl ethanol amine (2-(4
      Chlorobenzyl amino) ethanol) compound from the methanolic extract of aerial parts
      of Scrophularia oxysepala using by high performance liquid chromatographyare
      based on isocratic and liner gradients by C18 column. The structure elucidations
      of the isolated compounds were performed by spectroscopic methods including1H
      NMR, 13C-NMR, 2 D NMR technique such as HMBC( in deuterated methanol as solvent),
      GC-MS and UV, also methanolic extract and fractions( fractionated on solid phase
      extraction on C18 cartridge(Spack-C18)) of this plant was tested for free radical
      scavenging properties toward the 1, 1-diphenyl-1-picrylhydrazyl (DPPH), general
      toxicity (Brine shrimp toxicity assay) , insecticidal ( Contact toxicity
      insecticidal assay) and antimalarial activities (hemebiocrystallization
      inhibition assay).

PMID- 28496488
TI  - Purification, Characterization and Antioxidant Activities of Enzymolysis
      Polysaccharide from Grifola frondosa.
AB  - Our previous study revealed that the antioxidant activity of polysaccharide
      (coded as FGFP) extracted from Grifola frondosa by enzymolysis treatment was
      significantly superior than that (coded as GFP) extracted by boiling-water. In
      this study, one purified polysaccharide fractions (coded as FGFP-11) was obtained
      from FGFP by purified using DEAE-52 column and Sephacryl S-500HR column. Results
      indicated that FGFP-11 with MW of 59.82 kDa consisted of mannose, glucose and
      galactose with a molar ratio of 1.00:16.36:5.25. Fourier Transform Infrared
      Spectroscopy (FTIR spectrum) of FGFP-11 was similar with that of polysaccharide
      extracted by boiling-water from Grifola frondosa. These indicated the enzymolysis
      did not destroy the polysaccharide structure. NMR spectrum showed that FGFP-11
      possess alpha-(1->6) glycosidic bond and alpha-(1->3) glycosidic bond
      configuration. The experiment of Congo red also revealed that FGFP-11 had triple
      helix stereo-configuration. Moreover, the antioxidant activities of FGFP-11 were
      improved compared with that of GFP, especially in scavenging of hydroxyl radical
      and diphenyl picryl hydrazinyl (DPPH) radical.

PMID- 28496489
TI  - Homoisoflavonoids and the Antioxidant Activity of Ophiopogon japonicus Root.
AB  - The root of Ophiopogon japonicus has been used as a traditional Chinese medicine
      and also a functional food ingredient for a long time in China. In the present
      study, 17 different homoisoflavonoid compounds were identified in the root
      extract of O. japonicus by HPLC-DAD and LCMS/MS analyses. The antioxidant
      activity of the of chloroform/methanol (1:1, v/v), methanol and 70% ethanol
      extracts, and two major isolated homoisoflavonoid compounds
      (methylophiopogonanone A and methylophiopogonanone B) from O. japonicus root were
      investigated by various in-vitro assays. Methylophiopogonanone B showed the
      highest antioxidant ability according to four antioxidant methods. Among the
      extracts, the chloroform/methanol extract which contained high amounts of
      homoisoflavonoids was found to exhibit the strongest antioxidant activity. The
      results showed that O. japonicus root can be regarded as a potential source of
      homoisoflavonoids and natural antioxidant.

PMID- 28496490
TI  - Chitin from the Mollusc Chiton: Extraction, Characterization and Chitosan
      Preparation.
AB  - This study presents the first ever data of extracting chitin from the Chiton
      shell, which was then converted to the soluble chitosan by soaking in the 45%
      NaOH solution. The obtained chitin and chitosan were characterized by the seven
      different methods. Antioxidant activity of the extracted chitosan was also
      evaluated using the two methods. The shell content was divided into calcium
      carbonate (90.5 %), protein (5.2%), and chitin (4.3 %). Due to the results of
      element analysis and 1H NMR, the final degree of deacetylation of chitosan was
      90%. Surprisingly, a significant amount of Fe was accidentally found in the shell
      after demineralization, and removed from the solution through the filtering.
      Nonetheless, remained Fe in the extracted chitin and chitosan was 20 times higher
      than those previously reported from the shell of shrimps and crabs. Presence of
      this amount of Fe could describe why the produced chitosan was darker compared to
      the commercial chitosan. Antioxidant activity tests showed that the IC50 of the
      extracted chitosan was higher than one estimated for the commercial chitosan.
      Antioxidant activity of the extracted chitosan is even better than the commercial
      version and may be used in pharmaceutical industry as a source of antioxidant.

PMID- 28496491
TI  - The Effects of Transdermal Estrogen Delivery on Bone Mineral Density in
      Postmenopausal Women: A Meta-analysis.
AB  - Due to its minimal systematic adverse effects, transdermal estrogen is widely
      used for the prevention of osteoporosis in postmenopausal women. The present meta
      analysis aimed to clarify the effects of transdermal estrogen on bone mineral
      density (BMD) of postmenopausal women. Studies were identified by searching
      electronic databases including Cochrane Library, MEDLINE, Embase , and CINAHL
      databases, and also the Sciences Citation Index. Systematic review of articles
      was published between January 1989 to February 2016.Reference lists of the
      included articles were also evaluated and consultations were made with relevant
      experts. While 132 studies included the desired keywords, only nine clinical
      trials met the inclusion criteria and were finally reviewed. The pooled percent
      change in BMD was statistically significant in favor of transdermal estrogen.
      According to resulting pooled estimate, lumbar spine BMD one and two years after
      transdermal estrogen therapy was respectively 3.4% (95% CI: 1.7-5.1) and 3.7%
      (95% CI: 1.7-5.7) higher than the baseline values. The test for heterogeneity was
      not statistically significant based on the I2 heterogeneity index. One-two years
      of transdermal estrogen delivery can effectively increase BMD and protect the
      bone structure in postmenopausal women.

PMID- 28496493
TI  - Relationship Between the Provision of Injection Services in Ambulatory Physician
      Offices and Prescribing Injectable Medicines.
AB  - Overuse of injections is a common problem in many low-income and middle income
      countries. While cultural factors and attitudes of both physicians and patients
      are important factors, physicians> financial intensives may play an important
      role in overprescribing of injections. This study was designed to assess the
      effects of providing injection- services in physicians> ambulatory offices on
      prescribing injectable medicines. This cross-sectional study was conducted in
      Tehran in 2012 -2013and included a random sample of general physicians,
      pediatricians and infectious disease specialists. We collected data on the
      provision of injection services in or in proximity of physician offices, and
      obtained data from physicians> prescriptions in the previous three-month period.
      We analyzed the data using ANOVA, Student>s t-test and linear regression methods.
      We obtained complete data from 465 of 600 sampled physicians. Overall 41.9% of
      prescriptions contained injectable medicines. 75% of physicians offered injection
      services in their offices. Male physicians and general physicians were more
      likely to offer the services, and more likely to prescribe injectables. We
      observed a clear linear relationship between the injection service working hours
      and the proportion of prescriptions containing injectables (p-value<0.001).
      Providing injection service in the office was directly linked with the proportion
      of prescriptions containing injectables. While provision of injection services
      may provide a direct financial benefit to physicians, it is unlikely to be able
      to substantially reduce injectable medicines> prescription without addressing the
      issue.

PMID- 28496492
TI  - Infective endocarditis; report from a main referral teaching hospital in Iran.
AB  - BACKGROUND/OBJECTIVE: The aim of the present preliminary study was to assess the
      demographic, clinical, paraclinical, microbiological, echocardiographic, and
      therapeutic profile as well as in-hospital outcome of patients with infective
      endocarditis at a referral center for various infectious diseases in Iran.
      METHODS: Required demographic, clinical, plausible complications and paraclinical
      data were collected from patients' medical charts. Echocardiographic findings
      were obtained by performing transthoracic and/or transesophageal echocardiography
      as clinically indicated. In addition, details of management modalities and in
      hospital outcome of patients were recorded. RESULTS: During a 3-year period, 55
      patients with definite or possible diagnosis of Infective endocarditis were
      admitted to the ward. Twenty one (38.2%) patients were injection drug users.
      Staphylococcus aureus and S.epidermidis were the most commonly isolated
      microorganisms. Management modalities of Infective endocarditis included
      antimicrobial therapy alone (48 cases) and the combination of antimicrobial
      therapy and surgery (7 cases). CONCLUSION: The rate of negative blood culture in
      our cohort is high. S. aureus and S.epidermidis were the most commonly isolated
      microorganisms from positive blood cultures. Congestive heart failure was the
      most frequent infective endocarditis complication as well as indication for
      surgery. In-hospital mortality rate of patients was unexpectedly low.

PMID- 28496494
TI  - Effect of Inhalation of Lavender Essential Oil on Vital Signs in Open Heart
      Surgery ICU.
AB  - This study evaluated the effects of inhalation of Lavender essential oil on vital
      signs in open heart surgery ICU. The main complaint of patients after open-heart
      surgery is dysrhythmia, tachycardia, and hypertension due to stress and pain. Due
      to the side effects of chemical drugs, such as opioids, use of non-invasive
      methods such as aromatherapy for relieving stress and pain parallel to chemical
      agents could be an important way to decrease the dose and side effects of
      analgesics. In a multicenter, single-blind trial, 40 patients who had open-heart
      surgery were recruited. Inclusion criteria were full consciousness, lack of
      hemorrhage, heart rate >60 beats/min, systolic blood pressure > 100 mmHg, and
      diastolic blood pressure > 60 mmHg, not using beta blockers in the operating room
      or ICU, no history of addiction to opioids or use of analgesics in regular,
      spontaneous breathing ability and not receiving synthetic opioids within 2 h
      before extubation. Ten minutes after extubation, the patients> vital signs
      [including BP, HR, Central Venous Pressure (CVP), SPO2, and RR] were measured.
      Then, a cotton swab, which was impregnated with 2 drops of Lavender essential oil
      2%, was placed in patients' oxygen mask and patients breathed for 10 min. Thirty
      minutes after aromatherapy, the vital signs were measured again. Main objective
      of this study was the change in vital sign before and after aromatherapy.
      Statistical significance was accepted for P < 0.05. There was a significant
      difference in systolic blood pressure (p > 0.001), diastolic blood pressure (p =
      0.001), and heart rate (p = 0.03) before and after the intervention using paired
      t-test. Although, the results did not show any significant difference in
      respiratory rate (p = 0.1), SpO2 (p = 0.5) and CVP (p = 0.2) before and after
      inhaling Lavender essential oil. Therefore, the aromatherapy could effectively
      reduce blood pressure and heart rate in patients admitted to the open heart
      surgery ICU and can be used as an independent nursing intervention in stabilizing
      mentioned vital signs. The limitations of our study were sample size and lack of
      control group. Randomized clinical trials with larger sample size are
      recommended.

PMID- 28496495
TI  - Cortical Alpha Activity in Schizoaffective Patients.
AB  - Objective: Electrophysiological studies have identified abnormal oscillatory
      activities in the cerebral cortex in schizophrenia and mood disorders. Biological
      and pathophysiological evidence suggests specific deficits in serotonin (5-HT)
      receptor function in schizoaffective disorder (SA), a clinical syndrome with
      characteristics of both schizophrenia and bipolar disorder. This study
      investigated alpha oscillations in patients with SA. Method:
      Electroencephalography was used to measure ongoing and evoked alpha oscillations
      in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth
      Edition (DSM-IV) criteria for SA, and in 39 healthy controls. Results:
      Spontaneous alpha power of the participants with SA was significantly lower than
      that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity
      was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025].
      Conclusion: A strong reduction of alpha power in the posterior regions may
      reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and
      reduced cerebral blood flow is associated with reduced alpha activity among
      different regions of the brain. Therefore, it can be concluded that greatly
      decreased alpha activity, particularly in centro-parietal and occipital regions,
      is related to SA symptoms such as hallucinations.

PMID- 28496496
TI  - Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits
      and Obsessive-Compulsive Behavior in Rats.
AB  - Objective: This study was designed to examine the effect of environmental
      enrichment during methamphetamine (METH) dependency and withdrawal on
      methamphetamine-induced spatial learning and memory deficits and obsessive
      compulsive behavior. Method: Adult male Wistar rats (200 +/- 10 g) chronically
      received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals) for 14
      days. Rats reared in standard (SE) or enriched environment (EE) during the
      development of dependence on METH and withdrawal. Then, they were tested for
      spatial learning and memory (the water maze), and obsessive-compulsive behavior
      as grooming behavior in METH-withdrawn rats. Results: The results revealed that
      the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on
      the water maze and displayed significantly increased proximity to the platform
      compared to their control groups. METH withdrawn rats reared in EE displayed less
      grooming behavior than METH/SE group. Conclusion: Our findings revealed EE
      ameliorates METH-induced spatial memory deficits and obsessive-compulsive
      behavior in rats.

PMID- 28496497
TI  - Investigation of Content and Face Validity and Reliability of Sociocultural
      Attitude towards Appearance Questionnaire-3 (SATAQ-3) among Female Adolescents.
AB  - Objective: This study aimed to determine the psychometric properties of
      sociocultural attitude towards appearance questionnaire in female adolescents.
      Method: This was a methodological study. The English version of the questionnaire
      was translated into Persian, using forward-backward method. Then the face
      validity, content validity and reliability were checked. To ensure face validity,
      the questionnaire was given to 25 female adolescents, a psychologist and three
      nurses, who were required to evaluate the items with respect to problems,
      ambiguity, relativity, proper terms and grammar, and understandability. For
      content validity, 15 experts in psychology and nursing, who met the inclusion
      criteria, were required. They were asked to assess the qualitative of content
      validity. To determine the quantitative content validity, content validity index
      and content validity ratio were calculated. At the end, internal consistency of
      the items was assessed, using Cronbach's alpha method. Results: According to the
      expert judgments, content validity ratio was 0.81 and content validity index was
      0.91. Besides, the reliability of the questionnaire was confirmed with Cronbach's
      alpha = 0.91, and physical and developmental areas showed the highest reliability
      indices. Conclusion: The aforementioned questionnaire could be used in researches
      to assess female adolescents' self-concept. This can be a stepping-stone towards
      identification of problems and improvement of adolescents' body image.

PMID- 28496498
TI  - Effectiveness of Psychoeducational Group Training on Quality of Life and
      Recurrence of Patients with Bipolar Disorder.
AB  - Objective: Bipolar disorder (BD) is a disabling psychiatric disorder with
      frequent recurrences. Besides pharmacotherapy, psychoeducation could be helpful
      in reducing symptoms as well as recurrence of this disorder, leading to
      improvement of patients' quality of life. This study aimed at investigating the
      effectiveness of a culturally adjusted structured program for training Iranian BD
      patients. Method: In a 6-month course (spring and summer 2014), 24 BD patients,
      visiting the outpatient clinic of Ibn-Sina Hospital in Mashhad and experiencing
      euthymic phase, were allocated in to 2 groups of intervention and control. The
      intervention group received 8 sessions of psychoeducation in four weeks. Patients
      in the control group received the usual treatment. The patients were evaluated
      with Hamilton Depression Rating Scale, Young Mania Rating Scale, and Short Form
      36 before the intervention and 4 weeks later, and the results were compared using
      independent t test. The patients were reexamined after 6 months for recurrence,
      hospitalization, treatment adherence, and visiting a psychiatrist, and were
      compared with patients in the control groups. Results: There was a significant
      difference in the intervention group in improvement in quality of life before and
      after treatment (p<0.003). In addition, the difference was significant between
      the 2 groups in the number of recurrence (p<0.001) and hospitalization (p<0.000)
      in 6 months. Conclusion: In addition to pharmacotherapy, psychoeducation of
      patients with BD can improve their quality of life and decrease the risk of
      disorder recurrence.

PMID- 28496500
TI  - Transition of Mental Health to a More Responsible Service in Iran.
AB  - Objective: This study proposed a model for provision of an effective universal
      coverage for mental health services based on global and national experiences,
      available resources and the nature of primary health care system of Iran to
      reduce the burden of mental health conditions. Method: A framework with
      prioritized mental and social health services was devised through a review of
      literature and policy documents. It was then adapted using inputs from the
      stakeholders and experts. Results: The new model included 2 basic and specialized
      service strata: a PHC-based infrastructure and essential requirements needed to
      establish the service. Our proposed socio-mental health approach is based on a
      WHO recommendation. Conclusion: The key features of the model, which is going to
      be tested in a pilot study in 2015, are setting up a system for organized
      referrals to specialized mental facilities and compatibility with the existing
      primary health care system. Moreover, to achieve this goal, socio-mental health
      technicians should be employed.

PMID- 28496499
TI  - Psychiatric Comorbidities and Environmental Triggers in Patients with Chronic
      Daily Headache: A Lifestyle Study.
AB  - Objective: Patients with chronic daily headache (CDH) suffer from several
      significant psychiatric comorbidities and have unhealthy lifestyle. We aimed at
      studying psychiatric comorbidities, environmental triggers, lifestyle factors,
      and intensity of CDH in patients referred by the department of neurology from
      2011 to 2014. Method: Through medical and psychiatric interviews and using 0 to
      10 visual analogue scale (VAS), we assessed patients with CDH, using a checklist,
      to elicit psychiatric comorbidities, intensity of CDH, environmental factors, and
      lifestyle derangement. Results: We interviewed 413 (age 16-80 years, mean 40 +/-
      14.0) out of 548 patients; 312 (75.5%) were married, and 282 (68.1%) were female.
      Environmental triggers (374, 90.6%) were the most common cause of CDH, while 214
      (51.8%) had no compliance to recommended nutrition. Exercise avoidance (201,
      48.7%) was the less prevalent lifestyle factor. Of the patients, 372 (90.1%) were
      stressed and 162 (39.2%) had obsessive-compulsive disorder (OCD), which were the
      most and less prevalent psychiatric comorbidities, respectively. Intensity of
      pain was moderate to severe (mean score = 7.1+/- 1.9), while females reported
      higher VAS scores (p<0.02). Patients with previous history of psychotherapy
      reported higher score of VAS (p<0.001). Those patients living with a person
      suffering from head pain reported more VAS score (p<0.003). Conclusion: Notable
      psychiatric comorbidities were found in patients with CDH, many of which are
      modifiable such as environmental triggers and unhealthy lifestyle. In heavily
      populated cities, these factors may double the burden of the CDH by precipitating
      new or exacerbating previous psychiatric comorbidities. We, thus, suggest
      conducting more studies on this subject.

PMID- 28496501
TI  - Evaluation of Knowledge and Attitude of Parents of Attention
      Deficit/Hyperactivity Disorder Children towards Attention Deficit/Hyperactivity
      Disorder in Clinical Samples.
AB  - Objective: Knowledge and attitude of parents about attention
      deficit/hyperactivity disorder (ADHD) is an important factor in management of the
      disorder in children. This study investigates the parents' knowledge and attitude
      towards ADHD, its symptoms, diagnosis, treatment and prognosis. Method: In this
      cross-sectional descriptive study, the subjects were 150 parents (120 mother and
      30 father) of ADHD children who were referred to a child psychiatry clinic
      affiliated in university of social welfare and rehabilitation sciences in Tehran.
      The diagnosis was made by a child psychiatrist according to DSM-IV TR criteria.
      The parents completed a 40 items questionnaire that was prepared by the authors
      and assessed their knowledge and attitude towards ADHD and source of their
      information. Results: The most common source of parent's information about ADHD
      was TV. The parent's knowledge about the symptoms of the disorder was relatively
      good. But in regard to diagnosis, treatment and prognosis of the disorder, they
      have very low knowledge and even incorrect beliefs. The parent's knowledge
      significantly correlated with their educational level (p=0.01). Conclusion: In
      general, knowledge of the parents was low and it can lead to misdiagnosis or
      mismanagement of this common and important disorder and need to further
      consideration in terms of educating parents about the disorder in media specially
      TV.

PMID- 28496502
TI  - The Effect of Creative Tasks on Electrocardiogram: Using Linear and Nonlinear
      Features in Combination with Classification Approaches.
AB  - Objective: Interest in the subject of creativity and its impacts on human life is
      growing extensively. However, only a few surveys pay attention to the relation
      between creativity and physiological changes. This paper presents a novel
      approach to distinguish between creativity states from electrocardiogram signals.
      Nineteen linear and nonlinear features of the cardiac signal were extracted to
      detect creativity states. Method: ECG signals of 52 participants were recorded
      while doing three tasks of Torrance Tests of Creative Thinking (TTCT/ figural B).
      To remove artifacts, notch filter 50 Hz and Chebyshev II were applied. According
      to TTCT scores, participants were categorized into the high and low creativity
      groups: Participants with scores higher than 70 were assigned into the high
      creativity group and those with scores less than 30 were considered as low
      creativity group. Some linear and nonlinear features were extracted from the
      ECGs. Then, Support Vector Machine (SVM) and Adaptive Neuro-Fuzzy Inference
      System (ANFIS) were used to classify the groups. Results: Applying the Wilcoxon
      test, significant differences were observed between rest and each three tasks of
      creativity. However, better discrimination was performed between rest and the
      first task. In addition, there were no statistical differences between the second
      and third task of the test. The results indicated that the SVM effectively
      detects all the three tasks from the rest, particularly the task 1 and reached
      the maximum accuracy of 99.63% in the linear analysis. In addition, the high
      creative group was separated from the low creative group with the accuracy of
      98.41%. Conclusion: the combination of SVM classifier with linear features can be
      useful to show the relation between creativity and physiological changes.

PMID- 28496503
TI  - Sexual Therapy for Women with Multiple Sclerosis and Its Impact on Quality of
      Life.
AB  - Objective: Multiple Sclerosis (MS) is a disease with a detrimental effect on
      functional status. The present study investigated the effect of a sexual therapy
      program on the quality of life (QOL) of women with multiple sclerosis. Method:
      Women with multiple sclerosis and sexual dysfunction (n = 30) were selected, and
      were randomly assigned into the treatment (n = 15), or the control groups (n =
      15). Participants of the treatment group (n = 15) received 12 weekly sessions of
      sexual therapy. Participants in both groups completed the Female Sexual Function
      Inventory (FSFI) and the MS Quality of Life- 54 (MSQOL-54) in the onset of the
      program and at the end of the program. Results: ANCOVA(s) using pre-test scores
      as covariate(s) revealed that in comparison to the control condition, MS patients
      within the treatment group showed a significant improvement in their sexual
      desire (0.0001), arousal (0.022), lubrication (0.001), orgasm (0.001),
      satisfaction (0.0001), overall quality of life (0.001), energy (0.023), cognitive
      function (0.005), and social function (0.001) at the end of the program. In
      addition, they were less limited in their roles due to the emotional and health
      problems. Conclusion: The present study revealed that addressing sexual
      dysfunction in MS patients could improve their quality of life. In the future,
      this research can extend its results, and apply the same method to men with MS to
      find whether sexual therapy enhances their quality of life.

PMID- 28496504
TI  - Epidemiology of Psychiatric Disorders in Iranian Children and Adolescents (IRCAP)
      and Its Relationship with Social Capital, Life Style and Parents' Personality
      Disorders: Study Protocol.
AB  - Objective: We aimed at designing a cross sectional study to investigate the
      prevalence of psychiatric disorders in Iranian children and adolescents (IRCAP)
      and to determine its relationship with social capital, life style, and parents'
      personality disorders. Method: This cross sectional study was a national project
      implemented in all provinces of Iran. In this community-based study, using
      multistage cluster sampling method, we selected 1000 children and adolescents
      aged 6 to 18 years in each province. The total sample size reached to 31 000. We
      randomly collected 170 blocks. Then, of each cluster head, we selected 6 cases
      including 3 cases of each gender in different age groups (6- 9 years, 10- 14
      years, and 15- 18 years). The clinical psychologists instructed the participants
      to complete the Persian version of Kiddie-Sads-Present and Lifetime Version (K
      SADS-PL). In addition, demographic data (gender, age, education, parent
      education, and economic situation) and information on lifestyle, social capital,
      and parents' personality disorders were obtained from the participants.
      Discussion: IRCAP study presents a protocol for an epidemiological survey on the
      first estimates for the prevalence of psychiatric disorders in children and
      adolescents across the country. This large body of data, on a range of individual
      behavioural and emotional items and scores, allows us to compare the rates and
      patterns of deviance between urban and rural places of residence in 31 provinces
      of Iran with non Iranian samples surveyed with the same measures.

PMID- 28496505
TI  - Suicide in Iran: The Facts and the Figures from Nationwide Reports.
AB  - Objective: Data on national rates of suicide is limited in Iran, preventing an
      action plan for health scope of suicide prevention. The current brief study was
      conducted to review available national published data on suicide and to interpret
      the probable discrepancies. Method: We evaluated all 20-year recent published
      original articles on committed suicides searching Iranian scientific databases,
      PubMed, and Google Scholar with the keywords of suicide, mortality, and Iran.
      Results: Articles showed an overall increased trend of suicidal deaths in Iran.
      Discrepancies existed regarding suicide rate and demographic characteristics
      among 9 English and Persian published articles. Although a suicide rate of 6.2
      per 100 000 was reported in 2003, almost 31 times greater than 1991, an average
      suicide rate of 9.9 per 100 000 was calculated based on data interpretations.
      Conclusion: Apparently, Iran has had the highest increase in suicide-related
      deaths among Eastern Mediterranean Region (EMR) and Islamic countries during the
      recent decades. National policies to prevent suicide have not been efficient
      enough, and urgent intervention is needed.?.

PMID- 28496506
TI  - Prevalence of Hypertension in Iran 1980-2012: A Systematic Review.
AB  - Background: The high prevalence of hypertension and concomitant increase in the
      risk of its related disease makes it an important health concern all over the
      world. Hypertension is one of the 5 global leading causes of mortality in the
      world. Little is known about the current prevalence of hypertension in Iran,
      however. This systematic review aimed to investigate the current prevalence of
      hypertension in Iran. Methods: A systematic review of hypertension was conducted
      using international databases, including Medline (PubMed) and Science Direct
      (Scopus), and Persian scientific databases. The searched keywords were
      "hypertension", "raised blood pressure", "prevalence", and "Iran". All original
      articles in English published from 1980 to 2012 were included. After data
      extraction, heterogeneity between studies and publication bias was assessed and
      effect size was pooled by the random effect model. Results: Forty-two studies
      with 402 282 subjects were included. The estimated prevalence of hypertension
      varied all around Iran (I2 = 99%). The overall pooled prevalence of hypertension
      was 22% (95%CI: 20.2 - 23.8). The prevalence of hypertension was 23.6% (95%CI:
      21.1 - 26.1) in men and 23.5% (95%CI: 20.2 - 23.8) in women. In urban areas, the
      prevalence of hypertension was 22.1% (95%CI: 19.4 - 24.7). Ten studies
      investigated the prevalence of hypertension in rural areas and according to the
      random effect model, the prevalence of hypertension in rural areas was 18.6%
      (95%CI: 13.6 - 23.6). Nonsignificant publication bias was found in this review (p
      value = 0.18). In our meta-regression analysis, only mean age and study quality
      were associated with significant variability. Conclusion: According to this
      study, hypertension is one of the most common health problems in Iran. Around one
      quarter of the adult population is hypertensive and its prevalence increases by
      aging. Timely and appropriate public health strategies are essential for the
      improvement of the screening, treatment, and control of hypertension.

PMID- 28496508
TI  - Venoplasty and Venous Stenting in Patients with Chronic Venous Insufficiency in
      the Lower Extremities.
AB  - Background: Venoplasty and stenting is a minimally invasive therapy that can be
      used for patients with deep venous insufficiency in the lower extremities. This
      study aimed at investigating the effect of venoplasty and venous stenting in
      patients with chronic venous insufficiency in the lower limbs. Methods: This
      prospective case-series study recruited patients with chronic deep venous
      insufficiency in the lower limbs candidated for venoplasty in the Vascular Clinic
      of Sina Hospital in Tehran, Iran. Venoplasty and stenting was done if the deep
      venous system in the lower extremities had stenosis or obstruction on venography.
      The patients were visited 1, 3, and 6 months after venoplasty to assess their
      symptoms, venous clinical severity, and venous disability. Primary and secondary
      patency was evaluated with Doppler ultrasound. Results: Seventy-three patients
      were included in the study. The follow-up of the patients' clinical symptoms
      showed significant improvement rates of about 90%, 88.7%, 92.5%, and 100% in
      claudication, edema, pain, and ulcers-respectively- only 1 month after the
      procedure. The stent patency rates were 93.2, 91.5, and 92.4 in the 1st, 2nd,
      3rd, and 6th postprocedural months, correspondingly. The venous clinical severity
      score and the venous disability score before the procedure were 14.2 and 2.73,
      respectively, which were decreased to 5 and 1.1, correspondingly, at 6 months'
      follow-up (p value < 0.001). Conclusion: Venoplasty and stenting in our patients
      with chronic deep venous insufficiency in the lower extremities conferred a
      significant improvement in clinical symptoms and a high percentage of patency.

PMID- 28496507
TI  - Depression and Associated Factors in Patients with Implantable Cardioverter
      Defibrillators.
AB  - Background: Psychological problems such as depression constitute a dilemma that
      patients with the implantable cardioverter-defibrillator (ICD) usually encounter
      and may impact their quality of life. The purpose of this study was to evaluate
      the prevalence of depression among adults with the ICD and the relationship
      between depression and associated factors. Methods: Totally, 115 individuals with
      the ICD participated in this cross-sectional study in Tehran, Iran, and
      depression and other related risk factors were evaluated in them. Two
      questionnaires, one for demographic characteristics and the Beck Depression
      Inventory, were applied for data acquisition. The data were analyzed, and the
      factors associated with depression in the patients with the ICD were assessed.
      Results: The mean age of the study population was 59.85 +/- 11.46 years. Males
      comprised 88 (76.5%) and females 27 (23.5%) of the patients. The multivariate
      analysis on the 115 patients revealed that frequency of ICD shocks (OR = 1.08,
      95%CI: 1.02 - 1.10), male sex (OR = 2.28, 95%CI: 1.027 - 5.07), more hospital
      admissions (OR = 1.19, 95%CI: 1.11 - 1.25), smoking cessation (OR = 9.8, 95%CI:
      4.48 - 20.07), presence of ICD shocks (OR = 4.5, 95%CI: 2.45 - 7.38),
      dyslipidemia (OR = 2.8, 95%CI: 1.22 - 4.95), and family history of depression (OR
      = 6.4, 95%CI: 3.0 - 13.46) were significantly and independently associated with
      the Beck score classifications. Conclusion: These findings suggest that a poor
      psychosocial outcome in patients with the ICD may occur as a result of a variety
      of associated factors, most of which are predictable and preventable.

PMID- 28496509
TI  - Effects of the Health Belief Model (HBM)-Based Educational Program on the
      Nutritional Knowledge and Behaviors of CABG Patients.
AB  - Background: Reducing blood pressure through diet decreases the possibility of
      heart attacks, and lowering blood cholesterol can reduce the risk of coronary
      artery disease. The aim of the present study was to examine the effects of
      education based on the Health Belief Model on the dietary behavior of patients
      following coronary artery bypass graft surgery (CABG) at the Heart Surgery
      Department of Shahid Beheshti Hospital of Qom. Methods: In this semi-experimental
      clinical trial, data were collected on 64 patients, at an average age of 59.9 +/-
      7.26 years in the intervention group and 58.5 +/- 7.6 years in the control group.
      Seventy percent of the study subjects were male and 30% were female. Intervention
      and control groups were given a questionnaire, comprising 56 questions in 5
      parts. The educational intervention was aimed at creating perceived
      susceptibility and perceived severity in the intervention group. After 1 month.
      Both groups were tested, and the resulting data were analyzed to investigate the
      effects of the educational intervention on the nutritional knowledge and behavior
      of the patients. Results: According to the results, educational intervention
      caused a significant increase in the mean scores of knowledge (p value = 0.001),
      perceived severity (p value = 0.007), and perceived benefits and barriers (p
      value = 0.003) in the intervention group but did not cause a significant increase
      in the mean score of nutritional behavior (p value = 0.390). Conclusion:
      Education based on the Health Belief Model seems to be effective in improving
      nutritional knowledge, but more consistent and comprehensive educational programs
      are necessary in order to change behavior and improve nutritional behavior.

PMID- 28496511
TI  - Evaluation of Coronary Arteries in Non-Ischemic Cardiomyopathies: A Case Report.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a
      congenital cardiac disease with myocardial involvement, most probably right
      ventricular (RV) dysfunction, accounting for 20% of sudden cardiac deaths.
      Characterized by the fibro-fatty infiltration of the RV free wall, ARVD/C
      presents in adolescents with ventricular arrhythmias and heart failure symptoms
      and as biventricular failure in adults. The coronary risk in these patients is
      not clear. We present an incidental finding: the left anterior descending artery
      cut-off in a middle-aged man with ARVD/C. He had been under treatment for heart
      failure symptoms, which had decompensated frequently commencing 6 months earlier,
      and therefore he was scheduled for stem cell injection. He had no chest pain or
      coronary artery disease risk factors. Two-dimensional transthoracic
      echocardiography demonstrated RV enlargement with moderate to severe dysfunction
      and left ventricular ejection fraction (LVEF) of 35-40%, which was 45-50% two
      years before. Selective coronary angiography performed 8 years previously was
      normal but a new one revealed the cut-off of the left anterior descending artery
      at the proximal portion, for which percutaneous coronary intervention was
      performed and showed no significant lesion in the other vessels. One should
      consider coronary artery disease in uncontrolled heart failure with LVEF
      reduction, even in the absence of typical chest pain. It may not be the natural
      course of the underlying disease.

PMID- 28496510
TI  - Constrictive Pericarditis and Primary Amenorrhea with Syndactyly in an Iranian
      Female: Mulibrey Nanism Syndrome.
AB  - Mulibrey nanism is a rare autosomal recessive syndrome caused by a mutation in
      the TRIM37 gene with severe growth retardation and multiple organ involvement.
      Early diagnosis is important because 50% of the patients develop congestive heart
      failure owing to constrictive pericarditis, and this condition plays a critical
      role in the final prognosis. A 37-year-old female patient presented with symptoms
      of dyspnea on exertion and shortness of breath. She had severe growth failure and
      craniofacial dysmorphic feature. Cardiac evaluation showed constrictive
      pericarditis, moderate pulmonary hypertension, and mild pericardial effusion. The
      patient underwent pericardiectomy, but her thick and adhesive pericardium forced
      the surgeon to do partial pericardiotomy. Our report underlines the importance of
      attention to probable Mulibrey nanism when confronting patients with primary
      amenorrhea, growth retardation, and dysmorphic features. Early cardiac
      examination is of great significance in the course of the disorder, and patients
      must be pericardiectomized to relieve the symptoms and increase survival.

PMID- 28496512
TI  - Takayasu's Arteritis Presenting with Headache and Peripheral Facial Palsy: A Case
      Report.
AB  - Takayasu's arteritis (TA) is a rare case of granulomatous arteritis which mainly
      involves the aorta and its large branches. Although arterial hypertension is the
      most common feature of the disease in both adults and children, patients with TA
      may present with numerous clinical manifestations. Our patient was a 45-year-old
      woman, known to have hypertension from 3 years earlier following assessments made
      for severe headache. One year after the diagnosis of hypertension, she developed
      a left-sided lower motor neuron facial palsy, which was treated with oral
      corticosteroids (Prednisolone). Notably, the patient's headache was relieved
      after she took corticosteroid therapy. Transthoracic echocardiography revealed
      severe aortic insufficiency and aneurysmal changes in the ascending aorta, and
      she was referred to our center for further evaluation. In multi-slice computed
      tomography angiography, significant long stenosis of the left subclavian artery
      was seen and the diameter of the ascending aorta was 50 mm. The patient underwent
      the Bentall operation. The pathologic examination of the aortic wall specimen was
      compatible with giant cell aortitis and more in favor of TA with the ascending
      aortic aneurysm. At 6months' follow-up, the patient was in good condition and had
      almost recovered from facial palsy.

PMID- 28496513
TI  - Dog Footprint in the Heart.
AB  - Cardiac manifestations of the hydatid cyst are relatively uncommon. Cardiac
      involvement may lead to the compression of vital organs, pulmonary hypertension,
      pericardial effusion, and even anaphylaxis. A 45-year-old woman presented to the
      Emergency Department of Tehran Heart Center with chest pain. Cardiac examination
      revealed relatively muffled heart sounds. Echocardiography demonstrated a round
      echolucent well-defined mass (47 * 25 mm) on the base and the mid lateral wall of
      the left ventricle (LV) without septation. Computed tomography angiography and
      cardiac magnetic resonance imaging revealed a large (52 mm) exophytic mass
      originating from the lateral wall of the LV with upward growth between the left
      anterior descending artery (LAD) and the left circumflex artery with no LV cavity
      obliteration. Coronary angiography showed upward displacement in the LAD with
      significant compressive narrowing. The patient underwent mass resection and
      grafting of the LAD. During surgery after the incision of the pericardium, the
      hydatid cyst entity of the mass was revealed. Hydatid cysts covered the
      anterolateral surface of the LV with adhesion to the pericardium. The patient
      recovered from the surgery uneventfully. Pathology report and immunological
      assays confirmed the diagnosis. During a 6-month postoperative follow-up period,
      she remained asymptomatic with complete recovery and no recurrence.

PMID- 28496514
TI  - Anomalous Intercoronary Communication with Unidirectional Flow in the Absence of
      Obstructive Coronary Artery Disease: A Case Report.
AB  - Large intercoronary communications in the absence of obstructive coronary artery
      disease constitute a very rare coronary artery anomaly in which there is a
      readily visible connection between the 2 coronary arteries with a unidirectional
      or bidirectional blood flow; consequently, this anomaly may be misinterpreted as
      a functioning collateral vessel, indicative of an unrecognized proximal coronary
      artery occlusion. In contrast to collateral vessels that are seen in the presence
      of critical coronary artery stenosis and total occlusions, these arterial
      communications are vessels that are single, extramural, straight, and large in
      diameter. Myocardial ischemia could result from the coronary steal phenomenon by
      a unidirectional intercoronary communication. Herein, we describe a 57-year-old
      female with chest pain who was found in coronary angiography to have a single
      large intercoronary channel between the posterolateral branch of the right
      coronary artery and the distal left circumflex artery with a unidirectional flow.

PMID- 28496515
TI  - The importance of atrial anatomy.

PMID- 28496516
TI  - Effect of Corticosteroids on Pain Relief Following Root Canal Treatment: A
      Systematic Review.
AB  - INTRODUCTION: Post-operative pain and flare-up may occur in up to 58% of patients
      following root canal treatment. The aim was to conduct a systematic review and a
      possible meta-analysis to determine the effect of glucocorticosteroid (GCS) on
      pain following root canal treatment. METHODS AND MATERIALS: Scopus, MEDLINE and
      CENTRAL databases were searched up to 30th January 2017 with broad key words. In
      addition, the reference lists in eligible papers and text books were hand
      searched. Assessment of the eligibility of papers and data extraction were
      performed by two independent reviewers. RESULTS: Of 9891 articles, 18 were
      recruited as eligible papers. Most of these papers showed pain reducing effect of
      GCS on post-endodontic pain. Because of wide heterogeneity among the recruited
      papers, it was not possible to perform meta-analysis. CONCLUSION: Based on the
      results of this systematic review, there is a vast heterogeneity amongst articles
      regarding the use of GCS and their effect on post-operative pain after endodontic
      treatment. Further investigations with similar methods and materials are needed
      before meta-analysis on the effect of GCS on post-operative pain following root
      canal treatment can be performed.

PMID- 28496517
TI  - Root Canal Irrigants and Dentin Bonding: An Update.
AB  - The purpose of the review was to assess the effect of root canal irrigants on
      dentin bonding. A PubMed-based search was conducted on the articles published
      from 1980 to 2016. A brief overview and reviewing the effect on dentin bonding of
      common root canal irrigation solutions such as sodium hypochlorite (NaOCl),
      chlorhexidine (CHX), ethylenediaminetetraacetic acid (EDTA), mixture of a
      tetracycline, acid and a detergent (MTAD) and ozone was conducted. Findings
      showed that, depending on the type of dentin bonding, using NaOCl may decrease,
      increase or not affect the bond strength. In addition, due to its broad-spectrum
      matrix metalloproteinase-inhibitory effect, CHX as well as MTAD can significantly
      improve the resin-dentin bond stability. However, the effect of ozone therapy on
      bond strength was controversial.

PMID- 28496518
TI  - Cytotoxicity of Selected Nanoparticles on Human Dental Pulp Stem Cells.
AB  - INTRODUCTION: Nanoparticles are being increasingly applied in dentistry due to
      their antimicrobial and mechanical properties. This in vitro study aimed to
      assess and compare the cytotoxicity of four metal oxide nanoparticles (TiO2,
      SiO2, ZnO, and Al2O3) on human dental pulp stem cells. METHODS AND MATERIALS:
      Four suspension with different concentrations (25, 50, 75, 100 ug/mL) of each
      nanoparticle were prepared and placed into cavities of three 96-well plates
      (containing 1*104 cells per well that were seeded 24 earlier). All specimens were
      incubated in a humidified incubator with 5% CO2 at 37 degrees C. Mosmann's
      Tetrazolium Toxicity (MTT) assay was used to determine in vitro cytotoxicity of
      test materials on pulpal stem cells. Cell viability was determined at 24, 48, and
      72 h after exposure. Data comparisons were performed using a general linear model
      for repeated measures and Tukey's post hoc test. The level of significance was
      set at 0.05. RESULTS: The tested nanoparticles showed variable levels of
      cytotoxicity and were dose and time dependant. The minimum cell viability was
      observed in ZnO followed by TiO2, SiO2 and Al2O3. CONCLUSION: The results
      demonstrated that cell viability and morphological modifications occurred at the
      concentration range of 25 to 100 ug/mL and in all nanoparticles. The higher
      concentration and longer duration of exposure increased cellular death. Our
      results highlight the need for a more discrete use of nanoparticles for
      biomedical applications.

PMID- 28496519
TI  - Letter to the Editor.

PMID- 28496520
TI  - A Behavioral Process Model of Familism.
AB  - Familismo, or familism, an important Latino cultural construct associated with
      youth adjustment, describes the importance of family regarding support, comfort,
      and services. Increased research on familism among Latino families in the past
      decade has called for a theoretical process model of familism that can guide
      research on familism, family processes, and youth development. In this article,
      we propose the behavioral process model of familism (BPMF), which identifies
      proximal mechanisms through which familism is expected to promote youth
      psychological adjustment. Specifically, we propose that parenting behaviors
      (e.g., monitoring, discipline strategies) are a mechanism by which parent
      familism relates to youth familism and psychological adjustment both directly and
      via their familism-consistent behaviors. We hypothesize direct and mediated
      pathways in the BPMF and consider how sociodemographic variables modify the
      described processes.

PMID- 28496521
TI  - On-Chip Fluorescent Labeling using Reversed-phase Monoliths and Microchip
      Electrophoretic Separations of Selected Preterm Birth Biomarkers.
AB  - On-chip preconcentration, purification, and fluorescent labeling are desirable
      sample preparation steps to achieve complete automation in integrated
      microfluidic systems. In this work, we developed electrokinetically operated
      microfluidic devices for solid-phase extraction and fluorescent labeling of
      preterm birth (PTB) biomarkers. Reversed-phase monoliths based on different
      acrylate monomers were photopolymerized in cyclic olefin copolymer microdevices
      and studied for the selective retention and elution of a fluorescent dye and PTB
      biomarkers. Octyl methacrylate-based monoliths with desirable retention and
      elution characteristics were chosen and used for on-chip fluorescent labeling of
      three PTB biomarkers. Purification of on-chip labeled samples was done by
      selective elution of unreacted dye prior to sample. Automated and rapid on-chip
      fluorescent labeling was achieved with similar efficiency to that obtained for
      samples labeled off chip. Additionally, protocols for microchip electrophoresis
      of several off-chip-labeled PTB biomarkers were demonstrated in poly(methyl
      methacrylate) microfluidic devices. This study is an important step toward the
      development of integrated on-chip labeling and separation microfluidic devices
      for PTB biomarkers.

PMID- 28496522
TI  - Synthesis, characterisation and Pickering emulsifier performance of poly(stearyl
      methacrylate)-poly(N-2-(methacryloyloxy)ethyl pyrrolidone) diblock copolymer nano
      objects via RAFT dispersion polymerisation in n-dodecane.
AB  - A near-monodisperse poly(stearyl methacrylate) macromolecular chain transfer
      agent (PSMA macro-CTA) was prepared via reversible addition-fragmentation chain
      transfer (RAFT) solution polymerisation in toluene. This PSMA macro-CTA was then
      utilised as a stabiliser block for the RAFT dispersion polymerisation of a highly
      polar monomer, N-2-(methacryloyloxy)ethyl pyrrolidone (NMEP), in n-dodecane at 90
      degrees C. 1H NMR studies confirmed that the rate of NMEP polymerisation was
      significantly faster than that of a non-polar monomer (benzyl methacrylate, BzMA)
      under the same conditions. For example, when targeting a PSMA14-PNMEP100 diblock
      copolymer, more than 99% NMEP conversion was achieved within 30 min, whereas only
      19% BzMA conversion was obtained on the same time scale for the corresponding
      PSMA14-PBzMA100 synthesis. The resulting PSMA-PNMEP diblock copolymer chains
      underwent polymerisation-induced self-assembly (PISA) during growth of the
      insoluble PNMEP block to form either spherical micelles, highly anisotropic worms
      or polydisperse vesicles, depending on the target DP of the PNMEP chains.
      Systematic variation of this latter parameter, along with the solids content,
      allowed the construction of a phase diagram which enabled pure morphologies to be
      reproducibly targeted. Syntheses conducted at 10% w/w solids led to the formation
      of kinetically-trapped spheres. A monotonic increase in particle diameter with
      PNMEP DP was observed for such PISA syntheses, with particle diameters of up to
      462 nm being obtained for PSMA14-PNMEP960. Increasing the copolymer concentration
      to 15% w/w solids led to worm-like micelles, while vesicles were obtained at
      27.5% w/w solids. High (>=95%) NMEP conversions were achieved in all cases and 3
      : 1 chloroform/methanol GPC analysis indicated relatively high blocking
      efficiencies. However, relatively broad molecular weight distributions (Mw/Mn >
      1.50) were observed when targeting PNMEP DPs greater than 150. This indicates
      light branching caused by the presence of a low level of dimethacrylate impurity.
      Finally, PSMA14-PNMEP49 spheres were evaluated as Pickering emulsifiers.
      Unexpectedly, it was found that either water-in-oil or oil-in-water Pickering
      emulsions could be obtained depending on the shear rate employed for
      homogenisation. Further investigation suggested that high shear rates lead to in
      situ inversion of the initial hydrophobic PSMA14-PNMEP49 spheres to form
      hydrophilic PNMEP49-PSMA14 spheres.

PMID- 28496523
TI  - Probing the causes of thermal hysteresis using tunable Nagg micelles with linear
      and brush-like thermoresponsive coronas.
AB  - Self-assembled thermoresponsive polymers in aqueous solution have great potential
      as smart, switchable materials for use in biomedical applications. In recent
      years, attention has turned to the reversibility of these polymers' thermal
      transitions, which has led to debate over what factors influence discrepancies in
      the transition temperature when heating the system compared to the temperature
      obtained when cooling the system, known as the thermal hysteresis. Herein, we
      synthesize micelles with tunable aggregation numbers (Nagg) whose cores contain
      poly(n-butyl acrylate-co-N,N-dimethylacrylamide) (p(nBA-co-DMA)) and four
      different thermoresponsive corona blocks, namely poly(N-isopropylacrylamide)
      (pNIPAM), poly(N,N-diethylacrylamide) (pDEAm), poly(diethylene glycol monomethyl
      ether methacrylate) (pDEGMA) and poly(oligo(ethylene glycol) monomethyl ether
      methacrylate) (pOEGMA). By studying their thermoresponsive behavior, we elucidate
      the effects of changing numerous important characteristics both in the
      thermoresponsive chain chemistry and architecture, and in the structure of their
      self-assemblies. Our findings demonstrate large deviations in the reversibility
      between the self-assemblies and the corresponding thermoresponsive homopolymers;
      specifically we find that micelles whose corona consist of polymers with a brush
      like architecture (pDEGMA and pOEGMA) exhibit irreversible phase transitions at a
      critical chain density. These results lead to a deeper understanding of stimuli
      responsive self-assemblies and demonstrate the potential of tunable Nagg micelles
      for uncovering structure-property relationships in responsive polymer systems.

PMID- 28496524
TI  - Long-term stability and reusability of molecularly imprinted polymers.
AB  - Molecularly imprinted materials are man-made mimics of biological receptors.
      Their polymer network has recognition sites complementary to a substrate in terms
      of size, shape and chemical functionality. They have diverse applications in
      various chemical, biomedical and engineering fields such as solid phase
      extraction, catalysis, drug delivery, pharmaceutical purification, (bio)sensors,
      water treatment, membrane separations and proteomics. The stability and
      reusability of molecularly imprinted polymers (IPs) have crucial roles in
      developing applications that are reliable, economic and sustainable. In the
      present article the effect of crosslinkers, functional monomers and conditions
      for template extraction on the long-term stability and reusability of IPs was
      systematically investigated. Adsorption capacity, selectivity, morphology and
      thermal decomposition of eleven different l-phenylalanine methyl ester imprinted
      polymers were studied to reveal performance loss over 100 adsorption-regeneration
      cycles. Furthermore, crosslinker and functional monomer specific reversible and
      irreversible decomposition of imprinted polymers as a result of adsorbent
      regeneration were investigated through adsorption studies, electron microscopy,
      N2 adsorption and thermogravimetric analysis. A decomposition mechanism was
      proposed and revealed using NMR spectroscopy. Solutions to avoid or overcome the
      limitations of the most common crosslinkers, functional monomers and extraction
      techniques were proposed and experimentally validated.

PMID- 28496525
TI  - IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel
      Disease.
AB  - Very early onset inflammatory bowel disease (VEO-IBD) is a unique disease entity
      with a complex genetic susceptibility in affected patients. Next-generation gene
      sequencing techniques have revealed various monogenetic mutations contributing to
      the pathogenesis of VEO-IBD, including interleukin 10 (IL-10) and IL-10 receptor
      (IL-10R) mutations. In this article, we reviewed the features of and effective
      therapeutic options for VEO-IBD with IL-10 and/or IL-10R mutations. The IL-10
      signal pathway inhibits the release of several key cytokines and thereby has a
      significant anti-inflammatory effect in the gastrointestinal tract. Mutations of
      the genes encoding IL-10 and/or IL-10R have been detected in VEO-IBD patients
      among myriad populations throughout the world. VEO-IBD patients with IL-10 or IL
      10R mutations often present with repeated bouts of bloody diarrhea, marked weight
      loss, growth retardation, and recurrent perianal problems, including abscesses,
      fistulas, and significant fissures. Moreover, some patients may have folliculitis
      and present with pulmonary infections. While the therapeutic efficacy of
      immunosuppressants is typically poor in these patients, allogeneic hematopoietic
      stem cell transplantation (HSCT) has been reported to improve symptoms
      significantly. However, the long-term prognosis of VEO-IBD patients with IL-10 or
      IL-10R gene mutations treated with HSCT requires further exploration to verify
      the efficacy and safety of this treatment. We concluded that clinicians should
      recognize the clinical phenotype of VEO-IBD, as mutational analysis of the IL-10
      pathway can support the diagnosis and prompt early treatment of this complicated
      disease.

PMID- 28496526
TI  - Changing Trends in Age, Gender, Racial Distribution and Inpatient Burden of
      Achalasia.
AB  - BACKGROUND: Achalasia is an idiopathic esophageal motility disorder characterized
      by dysphagia, regurgitation, chest discomfort and weight loss. The aim of this
      study was to evaluate the temporal trends in demographic variables,
      interventions, and inpatient burden in achalasia-related hospitalizations.
      METHODS: We evaluated the National Inpatient Sample Database (NIS) for all
      patients in whom achalasia (ICD-9 code: 530.0) was the principal discharge
      diagnosis from 1997 to 2013. Data regarding the patient demographics, number of
      hospitalizations, length of stay, associated hospital costs and temporal trends
      over the study period were obtained. RESULTS: In 1997, there were 2,493
      admissions with a principal discharge diagnosis of achalasia as compared to 5,195
      in 2013 with an average increase of 4% per year (P < 0.001). In 1997, the
      proportion of patients under 65 years of age was 53.8% versus 60.1% in 2013.
      Increasing prevalence in African Americans was noted (11.1% to 17.1%). Inflation
      adjusted hospital charges related to achalasia showed a mean increase of $2,521
      per year (P < 0.001). There was an increase in Heller myotomy procedures over the
      study period (P < 0.001). CONCLUSIONS: The number of hospitalizations for
      achalasia and associated costs has significantly increased significantly over the
      last 16 years in the United States with disproportionate increase in patients
      under 65 years of age and racial minorities. Further research on cost-effective
      evaluation and management of achalasia is required.

PMID- 28496527
TI  - Correlation Between Symptom Severity and Health-Related Life Quality of a
      Population With Gastroesophageal Reflux Disease.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic disease with a
      negative impact on the quality of life. The aim of this study was to investigate
      the reflux symptoms and the health-related quality of life in a population with
      GERD. METHODS: Data from patients with GERD, according to the Montreal
      definition, were collected between January and December 2009. The enrolled
      patients were classified by different reflux symptoms according to the modified
      Chinese GERDQ. The general demographic data, the modified GERD impact scores and
      the SF-36 questionnaire scores of these groups of patients were analyzed.
      RESULTS: A total of 173 patients were enrolled, and the general data, endoscopic
      findings and lifestyle habits of the participants with different severity of
      heartburn or regurgitation were all similar. The patients with moderate severity
      of reflux symptoms had significant lower SF-36 scores than those with mild
      severity. The cases with advanced heartburn severity owned the lowest scores
      among all cases. The impact on the daily activity of each affected individual had
      a positive association with the stronger severity of reflux symptom. CONCLUSION:
      The life quality of a population with GERD achieved the meaningful declination in
      participants with the moderate severity of heartburn or regurgitation. The
      severity of the reflux symptoms had a greater impact on the normal daily activity
      of the patients with GERD. The cases with advanced severity of heartburn had the
      worst well-being.

PMID- 28496528
TI  - Long-Term Study of Children With ROME III Functional Gastrointestinal Disorders
      Managed Symptomatically in a Biopsychosocial Model.
AB  - BACKGROUND: Our study evaluated progression of and identified potential factors
      contributing to outcomes of ROME III defined-functional gastrointestinal
      disorders (FGIDs) in children treated symptomatically in a biopsychosocial model
      of care with a long-term follow-up. METHODS: We performed a retrospective review
      of pediatric patients who were diagnosed with ROME III defined-FGIDs including
      functional abdominal pain, functional dyspepsia, irritable bowel syndrome and
      abdominal migraine. Patients were managed symptomatically in a biopsychosocial
      model of care from the time of initial diagnosis. Demographics, management,
      progression and response to treatment assessed as complete, partial, and no
      improvement were reviewed. RESULTS: Two hundred fifty-eight patients were
      included with mean age of 10.6 years, female 55.4%, mean number of encounters 3.3
      visits, and mean follow-up was 18.7 months (range 2 - 59, SD 15.8). Diagnoses
      were functional abdominal pain 45%, irritable bowel syndrome 20.9%, multiple
      13.2%, functional dyspepsia 12.8%, and abdominal migraine 8.1%. Investigations
      were performed in most patients: laboratory studies in 93.4% (non-contributory
      abnormal 23.6%), imaging studies in 45.3% (non-contributory abnormal 5%) and
      endoscopies in 43.0% (non-contributory abnormal 1.2%). Treatment included
      medication in 93.7%, and surgery in 1.9% (normal pathology). There were new
      functional gastrointestinal diagnosis in 11.6%, evolution of FGIDs, from one to
      another in 12.0%, and recurrence found in 35.7% of patients. There were 60.1%
      patients in the complete improvement group (CIG) and 39.1% in the partial/no
      improvement group (PIG/NIG). No statistical difference was found between CIG and
      PIG/NIG regarding demographics or evaluation. PIG/NIG had more encounters (mean
      3.63 vs. 3.11; P = 0.03), had non-contributory lab abnormalities (34.4% vs.
      20.0%; P = 0.01), needed more endoscopies (52.4% vs. 36.8%; P = 0.02), required
      more treatment changes (mean 1.41 vs. 0.81; P < 0.01) and developed new
      functional gastrointestinal diagnoses (19.4% vs. 6.5%; P < 0.01) with long-term
      follow-up. CONCLUSIONS: Patients with ROME III defined-FGIDs who experience
      partial or no improvement with treatment develop new FGID diagnosis, need more
      number of follow-up visits, require more number of endoscopies, need more
      treatment changes, and have more non-contributory laboratory abnormalities,
      compared to those who experience complete improvement. Symptomatic treatment
      offered in a biopsychosocial model of care is possibly beneficial in managing
      children with FGIDs.

PMID- 28496529
TI  - Discontinuation of Scheduled Infliximab in Crohn's Patients With Clinical
      Remission: A Retrospective Single-Center Study.
AB  - BACKGROUND: It is crucial to determine whether infliximab (IFX) therapy could be
      safely interrupted in Crohn's disease (CD) patients with clinical remission. The
      outcome and risk predictors of relapse after IFX therapy stopped are
      controversial. The aim was to assess the relapse and predictive factors after IFX
      discontinuation in CD patients with clinical remission. METHODS: A retrospective
      cohort of CD patients with clinical remission who discontinued scheduled IFX
      therapy at Nanfang Hospital were included. The primary outcome was relapse. All
      patients were followed up for more than 3 months. Demographic, clinical, and
      laboratory parameters were evaluated for their predictive value of relapse.
      RESULTS: After a median follow-up period of 12.2(4.8 - 21.2) months, 55.7%
      (59/106) patients experienced a relapse. The cumulative relapse rate was 39%, 48%
      and 61% at 6 months, 1 year and 2 years, respectively. Based on multivariable
      analysis, CD-related surgery before infusion (P = 0.013, hazard ratio (HR):
      2.671, 95% confidential interval (CI): 1.230 - 5.798), step-up therapeutic
      regimen (P = 0.035, HR: 2.073, 95%CI: 1.054 - 4.080), low albumin (Alb) level at
      week 0 (P = 0.022, HR: 3.431, 95%CI: 1.196 - 9.846) and high C-reactive protein
      (CRP) level at week 30 (P = 0.007, HR: 2.643, 95%CI: 1.310 - 5.332) were
      associated with clinical relapse. CONCLUSIONS: After cessation of scheduled IFX
      therapy in CD patients with clinical remission, nearly half of the patients
      experienced a relapse within 1 year. In the event of the presence of certain
      predictive factors, IFX scheduled therapy should probably be continued.

PMID- 28496530
TI  - Assessment of the Relation Between SNP in MxA Gene and the Responsiveness of
      Egyptian HCV Genotype 4 Patients to Pegylated Interferon and Ribavirin Treatment.
AB  - BACKGROUND: Pegylated interferon (PegIFN) is used in the treatment of chronic
      hepatitis C virus (HCV) patients especially in resource limited countries.
      Treatment with PegIFN stimulates the expression of a number of host genes
      encoding enzymes with antiviral activities, including myxovirus resistance gene-A
      (MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at
      position -88 in the promoter region that affects the expression of MxA gene
      protein and was suggested to affect the treatment outcome. The aim of the work
      was to assess the relation between the SNP in the MxA gene and its impact on
      treatment of chronic HCV patients with PegIFN and ribavirin. METHODS: We
      therefore genotyped the biallelic G/T SNP in the promoter region of MxA gene at
      position -88 from the transcription start site by restriction fragment length
      polymorphism (RFLP) in 70 chronic HCV genotype 4 interferon naive Egyptians and
      40 healthy controls. RESULTS: G allele was the prevalent one in both HCV patients
      group (105, 74.5%) and control group (66, 82.5%), while T allele was less
      expressed in patients group (36, 25.5%) and control group (14, 17.5%). There is
      no correlation between genotypes and response to IFN-alpha therapy: GG (OR:
      0.958, 95% CI: 0.541 - 1.698, P = 0.884), GT (OR: 0.667, 95% CI: 0.188 - 2.362, P
      = 0.530), and TT (OR: 0.300, 95% CI: 0.083 - 1.090, P = 0.067). CONCLUSION: MxA
      nt-88 SNP did not affect the sustained virological response (SVR) rates after
      PegIFN and ribavirin combined treatment and did not act as a biological marker to
      potentially identify responders and non-responders to treatment. Our results call
      for additional large studies and/or meta-analysis of all currently available data
      to examine the role of MxA nt-88 SNP in predicting response to PegIFN and
      ribavirin in patients with IFN-alpha naive HCV genotype 4.

PMID- 28496531
TI  - Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity
      of Liver Damage at the Time of Transplantation.
AB  - BACKGROUND: We evaluated the concept of whether liver failure patients with a
      superimposed kidney injury receiving a simultaneous liver and kidney transplant
      (SLKT) have similar outcomes compared to patients with liver failure without a
      kidney injury receiving a liver transplantation (LT) alone. METHODS: Using data
      from the United Network of Organ Sharing (UNOS) database, patients were divided
      into five groups based on pre-transplant model for end-stage liver disease (MELD)
      scores and categorized as not having (serum creatinine (sCr) <= 1.5 mg/dL) or
      having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT,
      14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis.
      RESULTS: Survival in those (liver failure with renal dysfunction) receiving SLKT
      was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL
      (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD
      group with renal dysfunction with or without SLKT. In high MELD recipients (MELD
      > 30) with renal dysfunction, presence of renal dysfunction affects the outcome
      and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of
      renal dysfunction at the time of transplantation does affect post-transplant
      survival, but survival is improved with SLKT. CONCLUSIONS: SLKT improved 1-year
      survival only in low MELD (16 - 20) recipients but not in other groups.
      Performance of SLKT should be limited to patients where a benefit in survival and
      post-transplant outcomes can be demonstrated.

PMID- 28496532
TI  - Lack of Association Between the Clinical Outcome of Clostridium difficile
      Infection and Current Steroids Use.
AB  - BACKGROUND: The purpose of this study was to compare the outcome of Clostridium
      difficile infection (CDI) in patients on systemic steroids for various
      indications to patients not on steroids in term of disease severity, and
      associated morbidity and mortality. METHODS: We retrospectively reviewed records
      of all patients with CDI at our hospital from January 2011 to December 2016.
      Patients were evaluated for baseline characteristics, comorbidities, medications,
      disease severity, disease-related length of stay (LOS) from the diagnosis of CDI
      to discharge, need for surgical intervention, and disease-related mortality.
      Based on systemic steroids use, patients who were using steroids for different
      indications constituted the study population, and those with no steroids use were
      clustered as a control group. RESULTS: Of the 258 patients included, males were
      127 (49%). Severe and severe-complicated CDI developed in 21/63 (33.3%) and 1/63
      (1.6%) of patients on steroids (average daily dose of 20 mg), and in 73/195
      (37.4%) and 5/195 (2.6%) of patients with no steroids use (P = 0.56 and P = 0.66,
      respectively). Surgical intervention was not required in the steroids group and
      5/195 (2.7%) of patients not on steroids underwent bowel surgeries (P = 0.38).
      Mean LOS (days) was 11.6 +/- 1.5 in the steroids group and 10.4 +/- 0.7 in the no
      steroids group (P = 0.4). CDI-related mortality occurred in 9/63(14.3%) of
      patients on steroids, and in 15/195 (7.7%) of patients not on steroids (P = 0.12;
      odds ratio (OR): 2; 95% confidence interval (CI): 0.8 - 4.8). CONCLUSION: There
      was no significant difference in the severity of CDI, need for surgical
      interventions, disease-related LOS and mortality in systemic steroids users
      compared to patients not on steroids.

PMID- 28496533
TI  - The Diagnostic Value of Alarm Features for Identifying Types and Stages of Upper
      Gastrointestinal Malignancies.
AB  - BACKGROUND: Upper gastrointestinal (GI) malignancies are an uncommon cause of
      dyspepsia but of great concern. The aim of this study was to determine the
      association between alarm features and each type and stage of upper GI
      malignancies. METHODS: Patients who underwent endoscopy for symptoms of dyspepsia
      between January 2008 and December 2009 were retrospectively collected. Alarm
      features studied in this study were dysplasia, body weight loss and GI bleeding.
      Patients were classified according to the findings of endoscopy and histological
      reports. RESULTS: A total of 3,926 patients were included in the study, with 82
      (2.1%) cases with GI malignancies. The specificity and negative predictive value
      of alarm features ranged from 93.8% to 99.8%, but the sensitivity and positive
      predictive value ranged from 11.6% to 29.3%. The only variable with a positive
      predictive value was dysphagia (66.7%). The patients with esophageal cancers and
      upper gastric cancers had the highest ratio of alarm features, most body weight
      loss and dysphagia. There was a positive correlation between alarm features and
      advanced stages of gastric cancers, with the exception of GI bleeding sign.
      CONCLUSION: Although alarm features had a low sensitivity in identifying patients
      with upper GI malignancies, the presence of alarm features did help diagnose
      esophageal or upper gastric cancer and the sign of GI bleeding for early gastric
      cancer. In addition, dysphagia and weight loss are associated with higher stages
      of gastric cancer.

PMID- 28496534
TI  - Collagenous Gastritis in a Young Female With IgA Deficiency.
AB  - Collagenous gastritis, without colonic involvement, is exceptionally rare. It is
      not known to be associated with IgA deficiency and scleroderma. This is the first
      report of this type of association. We present a 26-year-old white female with a
      past medical history of gastroesophageal reflux disease and scleroderma. She was
      evaluated for complaints of abdominal pain and diarrhea.
      Esophagogastroduodenoscopy showed gastritis and duodenitis. Colonoscopy was
      normal. The histopathological report showed collagenous gastritis and focal
      lymphocytic duodenitis. A definitive treatment has not been established for this
      condition. Reporting such cases furthers understanding of the disease and will
      help to establish diagnostic criteria and to develop therapeutic strategies.

PMID- 28496535
TI  - Spontaneous Rupture of a Choledochal Cyst During Post Partum: A Rare
      Presentation.
AB  - With the advent of newer radiological investigations, choledochal cysts are being
      diagnosed more often in present era. These cysts are commonly diagnosed in early
      childhood and infancy, although some go undetected to be diagnosed in adulthood.
      These malformations are associated with multiple complications like cholangitis,
      jaundice, pancreatitis, rupture or even malignancy. Here we describe a post
      partum female, who was diagnosed to have choledochal cyst during sixth month of
      pregnancy. She presented with obstructive jaundice in cholangitis and was
      subjected to endoscopic retrograde cholangiopancreatography (ERCP) with stenting.
      This female delivered normally at term. She again had jaundice with cholangitis
      during early post partum period. Endoscopic stenting could be performed. She had
      features of peritonitis after 1 week of stenting. Investigations were performed
      and a diagnosis of spontaneous rupture of choledochal cyst was made. She
      underwent laparotomy and lavage with complete excision of the choledochal cyst
      and Roux-en-Y hepaticojejunostomy.

PMID- 28496536
TI  - Percutaneous Endoscopic Gastrostomy in a Patient With Continuous Intrathecal
      Baclofen Infusion Therapy.
AB  - Percutaneous endoscopic gastrostomy (PEG) is the method of choice in patients
      requiring long-term enteral tube feeding. In patients with intrathecal baclofen
      infusion therapy (IBT) pump implantation, infection via the skin and soft tissue
      may be an issue of concern. The introducer technique for gastrostomy tube
      insertion may be useful in reducing the risk of peristomal infection. Although
      the presence of a PEG tube has been reported as a risk factor for implantation
      site infection (for newly inserted IBT pumps), whether existing IBT pumps are at
      risk for infection during or after the placement of a PEG tube is not clear. We
      report a case where PEG was successfully performed using the introducer technique
      on a patient with an IBT pump implant.

PMID- 28496537
TI  - Post-Colonoscopy Colonic Perforation Presenting With Subcutaneous Emphysema: A
      Case Report.
AB  - Colonoscopy is performed for both diagnostic and therapeutic indications.
      Although rare, associated complications can be quite serious. The frequency of
      these complications depends mainly on the skills of the physicians doing the
      procedure, and the diagnostic or therapeutic indications. Major complications
      include adverse anesthetic related events, aspiration pneumonia, bleeding, and
      colonic perforation. We present a rare case of a post-colonoscopy perforation
      presenting with subcutaneous emphysema and free mediastinal, and intra-peritoneal
      air. The patient was successfully managed conservatively with complete resolution
      of symptoms.

PMID- 28496538
TI  - Iron Pill Gastritis: An Under Diagnosed Condition With Potentially Serious
      Outcomes.
AB  - Given the ubiquitous use of oral iron therapy, their side effects are often
      encountered and well recognized in clinical practice. However, iron pill
      gastritis remains an often under-reported and elusive diagnosis. An astute
      clinician should be aware of this condition in order to promptly discontinue oral
      iron and institute timely treatment. Here in, we present a case of a 46-year-old
      woman who presented to the gastroenterology clinic with vague epigastric pain and
      microcytic anemia. Esophagogastroduodenoscopy revealed multiple gastric erosions
      and non-bleeding gastric antral ulcer with biopsies showing excessive iron
      deposition suggestive of iron pill gastritis. We reviewed the clinical features,
      pathology, and treatment of iron pill gastritis along with the review of the
      literature.

PMID- 28496539
TI  - Efficacy and Safety of Direct-Acting Oral Anticoagulants Use in Acute Portal Vein
      Thrombosis Unrelated to Cirrhosis.
AB  - In acute portal vein thrombosis (APVT) unrelated to cirrhosis, anticoagulant
      therapy is classically started with low molecular weight heparin or vitamin K
      antagonists. New direct-acting oral anticoagulants (DOACs) are used in the
      treatment of venous thrombosis outside the splanchnic vascular bed, but not in
      the latter. We report a young female with APVT occurring in a non-cirrhotic liver
      linked to heterozygosity of factor V-Leiden and prothrombin G20210A gene
      mutations. Rivaroxaban was started, with total recanalization of the left and
      partial recanalization of the right portal vein branches, without complications.
      New DOACs do not need daily subcutaneous injections nor routinely blood
      coagulation control tests, making its use attractive, eventually increasing
      patient's compliance. If proved to be safe and effective in the future studies,
      its use may be extended to PVT treatment. This case shows that rivaroxaban was
      safe, not only prevented the extension of thrombosis in the portal tract, but
      also resolved PVT, at least partially.

PMID- 28496541
TI  - Atypical Presentation of Gastric Volvulus.
AB  - Gastric volvulus has been reported in all age groups; however, it is typically
      diagnosed in the elderly. Organo-axial volvulus is the most common type, followed
      by the mesentero-axial and the combined types. Depending on the etiology, gastric
      volvulus can also be classified as primary (idiopathic) or secondary. Treatment
      of acute gastric volvulus involves laparoscopic or endoscopic
      procedures/maneuvers, depending on the severity of symptoms and surgical
      eligibility of the patient. Chronic gastric volvulus is typically managed
      conservatively, although laparoscopic or endoscopic interventions can also be
      employed depending on the severity of presentation.

PMID- 28496540
TI  - Recombinant Factor VIIa Use for Endoscopic Retrograde Cholangiopancreatography
      With Sphincterotomy in a Patient With Choledocholithiasis and Unusual
      Coagulopathy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure that
      combines the use of endoscopy and fluoroscopy to diagnose and treat
      pancreaticobiliary disorders. The risks of ERCP include pancreatitis, infection,
      bleeding and perforation. Bleeding during ERCP typically develops after
      sphincterotomy, hence patients should be screened and tested for coagulopathy
      before undergoing ERCP. Coagulopathy is a major risk factor for ERCP-related
      bleeding. Inherited factor VII (FVII) deficiency is a rare autosomal recessive
      hemorrhagic disorder that can lead to significant coagulopathy and severe
      bleeding if not appropriately recognized and treated preoperatively. Clinically,
      the disease ranges between an asymptomatic state to lethal hemorrhage and the
      degree of FVII deficiency does not correlate with the severity of bleeding. The
      use of FVII replacement therapy has been reported to prevent bleeding during
      surgery. We present the first report of a patient with a rare cause of
      coagulopathy due to inherited FVII deficiency who successfully underwent ERCP
      with sphincterotomy without bleeding where we used recombinant factor VIIa before
      and after the procedure.

PMID- 28496542
TI  - Multiple Duodenal Lipomas as a Rare Cause of Upper Gastrointestinal Obstruction:
      Case Report and Literature Review.
AB  - Duodenal lipomas are rare benign tumors and pose a diagnostic challenge as their
      symptoms are non-specific. In this article, we reported a case of duodenal lipoma
      presenting as upper gastrointestinal obstruction and reviewed the literature on
      relevant clinical manifestation, diagnosis and treatment. Our review of
      literature indicated that multiple duodenal lipomas as a cause of upper
      gastrointestinal obstruction as reported here are extremely rare. The
      preoperative computed tomography and magnetic resonance imaging are the key to
      diagnosis, and surgical resection is the most effective means for the management
      of such duodenal lipomas.

PMID- 28496544
TI  - Hemodynamic Effects of Sodium-Glucose Cotransporter 2 Inhibitors.
AB  - It is widely accepted that obesity and type 2 diabetes mellitus (T2DM) increase
      the risk of heart failure (HF) independently of underlying coronary artery
      disease. The changes in myocardial structure or function associated with diabetes
      have been termed diabetic cardiomyopathy. Corresponding to changes in the risk
      factors for HF, an epidemiologic transition is underway from HF with a reduced
      ejection fraction to HF with a preserved ejection fraction. Hyperglycemia can
      damage the myocardium, even before diagnosis of diabetes, but intensive glycemic
      control has no impact on the risk of HF in patients with T2DM. Recent clinical
      studies have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors,
      which inhibit renal reabsorption of glucose, decrease the risk of HF in T2DM
      patients. The cardioprotective mechanisms involved appear to be multifactorial
      and have been the subject of considerable debate. This review focuses on the
      hemodynamic effects of SGLT2 inhibitors in T2DM patients and the mechanisms by
      which these drugs decrease the risk of HF.

PMID- 28496543
TI  - Combination Antifungal Therapy: A Review of Current Data.
AB  - The incidence of invasive fungal infections has been on the rise, particularly in
      transplant recipients and in patients with hematological malignancies and other
      forms of immunosuppression. There is a mismatch between the rate of antifungal
      resistance and the development of new antifungal agents. Based on this, the idea
      of combining antifungals in the treatment of invasive fungal infections appears
      tempting for many clinicians, particularly after many in vitro studies showed
      synergism between many antifungal agents. Several randomized controlled trials
      have been published regarding the efficacy and safety of combination of
      antifungals, but the high cost, the limited number of cases and the multitude of
      confounding factors lead in some instances to weak and sometimes contradictory
      results. The lack of consensus in many clinical scenarios raises the importance
      of the need for more studies about combination antifungal therapies and should
      incite infectious disease societies to develop specific recommendations for the
      clinicians to follow while approaching patients with invasive fungal infections.

PMID- 28496545
TI  - C-Reactive Protein and Frailty in the Elderly: A Literature Review.
AB  - Chronic inflammation is a well-established background process in many age-related
      diseases. Many recent studies investigate the use of various inflammatory
      biomarkers such as C-reactive protein (CRP), interleukin-6, and interleukin-1 as
      predictors of physical and cognitive performance among elders. The phenotype of
      frailty has also been associated with underlying inflammatory mechanisms. The aim
      of this article was to review the literature referring to the correlation of CRP
      serum levels and frailty in older individuals. We tried to identify all relevant
      publications regarding the relation of CRP as an index of frailty in the elderly
      and its potential use. Although many studies in the recent medical literature
      positively associate serum CRP levels and frailty in older individuals, some do
      not, and some raise some interesting questions and set the basis for future
      studies. The association of CRP and frailty in elder patients should be
      considered when clinicians interpret inflammatory biomarkers in various clinical
      settings in such patients. Well-designed, prospective clinical trials are
      warranted to better assess the role and pathophysiology of frailty in the elderly
      and its mechanisms as also the exact role of CRP as an inflammatory marker and as
      a prognostic index in this syndrome.

PMID- 28496546
TI  - The Epidemiology and Risk Factors for Postoperative Pneumonia.
AB  - Postoperative pneumonia is a common complication of surgery, and is associated
      with marked morbidity and mortality. Despite advances in surgical and anesthetic
      technique, it persists as a frequent postoperative complication. Many studies
      have aimed to assess its burden, as well as associated risk factors. However,
      this complication varies among the different surgical specialties, and there is a
      paucity of reports that comprehensively evaluate this complication. Therefore,
      the purpose of this study was to review the epidemiology and risk factors of
      postoperative pneumonia in the setting of: 1) general surgery; 2) cardiothoracic
      surgery; 3) orthopedic and spine surgery; and 4) head and neck surgery.

PMID- 28496547
TI  - Effect of Ezetimibe Monotherapy on Low-Density Lipoprotein Cholesterol and on
      Markers of Cholesterol Synthesis and Absorption in Japanese Patients With
      Hypercholesterolemia.
AB  - BACKGROUND: The aim of this study was to evaluate effect of ezetimibe monotherapy
      on serum low-density lipoprotein cholesterol (LDL-C) in Japanese patients and to
      investigate the association between changes of LDL-C and changes of markers for
      cholesterol synthesis and absorption. METHODS: Seventy-six hypercholesterolemic
      patients without statin therapy were enrolled and randomized to two groups, which
      were an ezetimibe group (group E, n = 44) and a control group without ezetimibe
      treatment that received diet therapy alone (group C, n = 32). The study period
      was 12 weeks. In group E, 10 mg of ezetimibe was administered daily after
      breakfast. Serum lipids were measured every 4 weeks, while lathosterol (a
      cholesterol synthesis marker) and campesterol and sitosterol (cholesterol
      absorption markers) were examined at baseline and at 12 weeks. RESULTS: A
      significant reduction of LDL-C was observed in group E at both 4 and 12 weeks
      (from 155 +/- 3.9 to 128 +/- 3.4 mg/dL and 132 +/- 3.9 mg/dL, respectively, both
      P < 0.01), associated with an increase of high-density lipoprotein cholesterol
      (HDL-C)at 12 weeks (from 53 +/- 1.3 to 55 +/- 1.5 mg/dL, P < 0.05) and no change
      of triglycerides. In contrast, none of these lipids changed in group C. An
      increase of lathosterol and a decrease of campesterol and sitosterol were
      observed in group E, while none of these markers changed in group C. When group E
      was divided into two subgroups according to the reduction of LDL-C, which were a
      good response group (reduction >= 20 mg/dL, DeltaLDL-C = -27.9 +/- 1.3 mg/dL, n =
      18) and a poor response group (reduction < 20 mg/dL, DeltaLDL-C = -3.7 +/- 2.5
      mg/dL, n = 26), baseline levels of campesterol and sitosterol were higher in the
      good response group. CONCLUSION: Ezetimibe monotherapy reduced LDL-C and
      increased HDL-C, with the reduction of LDL-C being greater in patients with
      higher levels of cholesterol absorption markers.

PMID- 28496548
TI  - Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Impact of Total
      Radiation Dose on Survival?
AB  - BACKGROUND: Effective symptom palliation can be achieved with low-dose palliative
      thoracic radiotherapy. In several studies, median survival was not improved with
      higher doses of radiation. More controversy exists regarding the impact of higher
      doses on 1- and 2-year survival rates. Therefore, a comparison of survival
      outcomes after radiotherapy with different biologically equivalent doses
      (equivalent dose in 2-Gy fractions, EQD2) was performed. METHODS: This was a
      retrospective single-institution study of 232 patients with small or non-small
      cell lung cancer. Most commonly 2 fractions of 8.5 Gy were prescribed (34%),
      followed by 10 fractions of 3 Gy or equivalent regimens (30%, EQD2 circa 33 Gy).
      The highest EQD2 consisted of 45 Gy. Intention-to-treat analyses were performed.
      RESULTS: Survival was significantly shorter with regimens of intended EQD2 < 33
      Gy, e.g., 2 fractions of 8.5 Gy (median 2.5 months compared to 5.0 and 7.5 months
      with EQD2 of circa 33 and 45 Gy, respectively). The 2-year survival rates were
      0%, 7% and 11%, respectively. In 128 prognostically favorable patients, median
      survival was comparable for the three different dose levels (6 - 8.3 months). The
      2-year survival rates were 0%, 10%, and 13%, respectively (not statistically
      significant). CONCLUSION: Although most of the observed survival differences
      diminished after exclusion of poor prognosis patients with reduced performance
      status and/or progressive extrathoracic disease, a slight increase in 2-year
      survival rates with higher EQD2 cannot be excluded. Because of relatively small
      improvements, a confirmatory randomized trial in this subgroup would have to
      include a large number of patients.

PMID- 28496549
TI  - Phosphodiesterase-5 Inhibitors Improve Clinical Outcomes, Exercise Capacity and
      Pulmonary Hemodynamics in Patients With Heart Failure With Reduced Left
      Ventricular Ejection Fraction: A Meta-Analysis.
AB  - BACKGROUND: Several studies have compared the use of phosphodiesterase-5 (PDE5)
      inhibitors sildenafil or udenafil with the placebo in patients suffering from
      pulmonary hypertension (PH) due to left chronic heart failure (CHF),
      corresponding to group 2 (PH due to left heart disease) of the PH classification
      (according to 2015 ESC/ERS guidelines for the diagnosis and treatment of PH). The
      results of the use of PDE5 inhibitors in the PH due to left heart disease were
      inconsistent and heterogeneous. Therefore, we carried out a meta-analysis to
      assess the effect of PDE5 inhibitors in this clinical setting, i.e., patients
      with left CHF. METHODS: A systematic search was conducted using the PubMed and
      Embase electronic archives. Studies had to be prospective randomized controlled
      trials (RCTs). In each of the RCTs admitted to meta-analysis, a comparison was
      made between a group of CHF patients taking a PDE5 inhibitor and a second group
      assigned a placebo. Studies were incorporated in the meta-analysis provided that
      they had sufficient information about two or more of the following clinical,
      ergospirometric or hemodynamic outcomes: the composite of all-cause death and
      hospitalization, adverse events, peak VO2, 6-min walking distance (6MWD), left
      ventricular ejection fraction (LVEF), E/e' ratio, mean pulmonary arterial
      pressure (mPAP), pulmonary arterial systolic pressure (PASP), and pulmonary
      vascular resistance (PVR). RESULTS: Fourteen studies enrolling a total of 928
      patients were incorporated in the meta-analysis. Among them,13 were RCTs and one
      was a subgroup analysis. Among patients with CHF with reduced left ventricular
      ejection fraction (HFREF, n = 555), a significant benefit was conferred by PDE5
      inhibitors against the risk of the composite endpoint of death and
      hospitalizations (odds ratio (OR): 0.28; 95% confidence interval (CI): 0.10 -
      0.74; P = 0.03). Furthermore, among HFREF patients, PDE5 inhibitors were
      associated with a significant improvement in peak VO2 (difference in means (MD):
      3.76 mL/min/kg; 95% CI: 3.27 - 4.25) as well as in 6MWD (MD: 22.7 m; 95% CI: 8.19
      - 37.21) and LVEF (MD: 4.30%; 95% CI: 2.18% to 6.42%). For patients with HFREF,
      PDE5 inhibitors caused a non-significant reduction in mPAP, while PASP was
      significantly reduced (MD: -11.52 mm Hg; 95% CI: -15.56 to -7.49; P < 0.001). By
      contrast, in the RCTs of patients with CHF with preserved left ventricular
      ejection fraction (HFpEF, n = 373), no benefit ensued from PDE5 inhibitor use
      regarding all of the investigated clinical, ergospirometric or hemodynamic
      endpoints. CONCLUSIONS: PDE5 inhibitors improved clinical outcomes, exercise
      capacity and pulmonary hemodynamics in patients with HFREF, but not in HFpEF.
      However, considering the relatively small size of the HFpEF subset enrolled so
      far in the RCTs that explored the PDE5 inhibitor effects, further research in
      this field is undoubtedly warranted.

PMID- 28496550
TI  - Efficacy and Safety of SGLT2 Inhibitors in Reducing Glycated Hemoglobin and
      Weight in Emirati Patients With Type 2 Diabetes.
AB  - BACKGROUND: SGLT2 inhibitors are a new class of drugs that act by inhibiting
      glucose reabsorption in the proximal renal tubules. Many trials have demonstrated
      their effectiveness in reducing glycated hemoglobin (HbA1c) and weight, but they
      have never been examined in Arab or Emirati populations. METHODS: We assessed the
      efficacy of SGLT2 inhibitors in reducing HbA1c and weight in our population and
      specifically in an Emirati cohort. We also assessed the effect on fasting blood
      glucose, blood pressure, lipid profile, serum creatinine, and side effects.
      RESULTS: The total number of patients was 307. The baseline HbA1c in the Emirati
      cohort was 8.9+/-1.7%, which dropped significantly to 8+/-1.5% at 6 months (P =
      0.0001). At 1 year, the mean HbA1c was 8+/-1.4%, which was significantly
      different from baseline (P = 0.0001). However, the change in mean HbA1c from 6
      months (8+/-1.5%) to 1 year (8+/-1.4%) was not statistically significant (P =
      0.88). A similar highly significant change was observed when comparing weights at
      baseline and 6 months in the Emirati population (85.7 +/- 17.8 kg vs. 84 +/- 17.2
      kg, P = 0.0001). Total cholesterol dropped significantly at 6 months (P = 0.008),
      as did low-density lipoprotein (LDL) (P = 0.005). CONCLUSIONS: The use of SGLT2
      inhibitors is associated with significant reductions in HbA1c and weight. Unlike
      all previous trials, the inhibitors significantly reduced total cholesterol and
      LDL. Larger trials are needed to reassess their effects on lipid parameters.

PMID- 28496551
TI  - Lack of Association Between Toxoplasma gondii Infection and Diabetes Mellitus: A
      Matched Case-Control Study in a Mexican Population.
AB  - BACKGROUND: Very little is known about the association between infection with
      Toxoplasma gondii (T. gondii) and diabetes mellitus. We perform an age- and
      gender-matched case-control study to determine the association of T. gondii
      infection and diabetes mellitus. METHODS: Cases included 156 patients with
      diabetes mellitus and 156 controls without diabetes mellitus who attended in two
      public clinics in Durango City, Mexico. Sera of cases and controls were tested
      for the presence of anti-Toxoplasma IgG and IgM antibodies using commercially
      available enzyme-linked fluorescence assays (ELFA). RESULTS: Anti-T. gondii IgG
      antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156
      controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P =
      0.18). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels in
      seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in
      seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10
      cases and five controls with seropositivity to anti-T. gondii IgG antibodies were
      positive for anti-T. gondii IgM antibodies. Stratification by gender showed
      similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and
      female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in
      male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 -
      31.19; P = 0.61). CONCLUSIONS: We conclude that there is not serological evidence
      of an association between T. gondii infection and diabetes mellitus in the
      studied subjects in Durango City, Mexico. Further studies to elucidate the role
      of T. gondii in diabetes should be conducted.

PMID- 28496552
TI  - Screening for Depressive and Anxiety Symptoms During Pregnancy and Postpartum at
      a Japanese Perinatal Center.
AB  - BACKGROUND: We examined the current status of depressive and anxiety symptoms in
      Japanese women during pregnancy and postpartum. METHODS: We asked 220 Japanese
      women who gave birth to singleton babies at term to answer the two self
      administered questionnaires (Whooley's two questions and two-item generalized
      anxiety disorder scale) at first, second and third trimester of pregnancy and 1
      month after delivery. RESULTS: The rates of women with depressive symptoms were
      common during the first trimester of pregnancy (25%) and the postpartum (17%),
      while the women with anxiety symptoms were common during the first trimester of
      pregnancy (36%). Eight percent women had histories of mental disorders, and 95%
      of them showed depressive and/or anxiety symptoms somewhere during pregnancy. Of
      the women who had depressive symptoms during postpartum, 86% showed depressive
      and/or anxiety symptoms somewhere during pregnancy. CONCLUSION: Screening for
      depressive and anxiety symptoms during pregnancy was suggested to be useful to
      detect high risk women of postpartum depression.

PMID- 28496553
TI  - Does Syncope Predict Mortality in Patients With Acute Pulmonary Embolism? A
      Retrospective Review.
AB  - BACKGROUND: Acute pulmonary embolism (APE) is a potentially fatal disease with
      high mortality. Prior studies have shown an increased frequency of central
      localization of the clot, right ventricular dysfunction and elevated troponin in
      patients who present with syncope and APE. Existing evidence regarding mortality
      and length of hospital stay in these patients is unclear. METHODS: We
      retrospectively reviewed electronic medical records of patients who were admitted
      in a tertiary care hospital in rural Upstate New York and diagnosed with APE from
      July 2014 to July 2016. Two hundred nineteen patients were reviewed in two
      groups: patients who presented with syncope and those without syncope. RESULTS:
      The prevalence of syncope was found to be 6.8% (15/219). Hypotension on admission
      was more common among patients with syncope compared to no syncope (26.7% and
      7.4%, respectively, P = 0.03). A clinically significant difference was found in
      30-day mortality among those with syncope versus no syncope (21.3% vs. 7.4%, P =
      0.096). No significant difference was found in length of stay (mean 6.7 days in
      patients with syncope vs. 6.4 without syncope, P = 0.783), central localization
      (26.7% with syncope vs. 43.2% without syncope, P = 0.21) or troponin elevation
      (46.2% in patients with syncope vs. 27.9% without syncope, P = 0.205). On
      multivariable analysis, hypotension was significantly higher among those with
      syncope (odds ratio: 5.23, P = 0.0148). CONCLUSION: This study suggests 30-day
      mortality may be higher among patients with syncope. It is important to risk
      stratify patients on admission in order to reduce mortality and morbidity
      associated with lethal disease.

PMID- 28496555
TI  - Effect of Acupressure, Acupuncture and Moxibustion in Women With Pregnancy
      Related Anxiety and Previous Depression: A Preliminary Study.
AB  - BACKGROUND: In this preliminary study, we examined the effect of acupressure,
      acupuncture and moxibustion (oriental treatments) to prevent of the
      relapse/deterioration of perinatal depression in women with pregnancy-related
      anxiety and previous depression. METHODS AND RESULTS: Between 2014 and 2016,
      there were 48 women with pregnancy-related anxiety and previous depression who
      had delivery at >= 22 weeks' gestation in our institute. Of these, oriental
      treatments were performed in eight and two women (totally 10, 21%) during
      pregnancy and postpartum, respectively. One of the 10 (10%) who received oriental
      treatments admitted depressive symptoms during pregnancy or postpartum, while 18
      of the rest 38 who did not receive oriental treatments admitted depressive
      symptoms (47%, P = 0.065). CONCLUSION: The oriental treatments may be useful for
      pregnant women who need perinatal mental health care.

PMID- 28496554
TI  - Relationship Between Body Mass Index and Obesity Awareness in School Students.
AB  - BACKGROUND: The primary aim was to assess the prevalence of overweight and
      obesity among the participants and its relationship to obesity awareness.
      METHODS: A cross-sectional study that included intermediate and high schools
      students was conducted between April 2014 and June 2015. Anthropometric
      measurements were obtained by the researchers and body mass index (BMI) was
      calculated. We used the obesity risk knowledge (ORK-10) scale to assess obesity
      awareness. Participants who answered >= 5 out of 10 questions correctly were
      considered to be aware. RESULT: A total of 528 students were enrolled (mean age,
      15.58 years). The mean BMI was 22.37 kg/m2, and 27.6% were either overweight or
      obese. The mean ORK-10 score was 3.15 and 25.4% were considered to be aware.
      Compared to those who were non-aware, participants in the aware group were more
      likely to be older (P < 0.001), male (P < 0.001), attend high school (P < 0.001),
      eat dinner with their families (P = 0.021), eat fruit at least daily (P = 0.027),
      and consider obesity to be a disease (P < 0.001). CONCLUSION: Only 25.4% of
      students who participated were considered to be aware about obesity. Those who
      were aware were more likely to be older male high school students.

PMID- 28496556
TI  - Epidemiological Profile of Hispanics Admitted With Acute Myocardial Infarction in
      Puerto Rico: The Experience of 2007, 2009 and 2011.
AB  - BACKGROUND: A limited number of studies have been published about coronary artery
      disease in Hispanics, particularly among the Puerto Rican population. The aim of
      this study was to present a clinical epidemiological profile and management
      practices in patients hospitalized in Puerto Rico with acute myocardial
      infarction (AMI). METHODS: This secondary data analysis from the Puerto Rico
      Cardiovascular Surveillance Study included 6,162 patients at 19 hospitals in
      Puerto Rico, during years 2007, 2009 and 2011. RESULTS: The mean age of the
      patients diagnosed with AMI was 67 +/- 13.6 years old, with women being older
      than men (P < 0.001). Women had a different risk factor burden when compared to
      men. Car/walked in was the principal mode of hospital transportation (65.9%).
      Women received less medications and cardiac procedures when compared to men.
      While no significant differences in length of hospital stay (LOS) were observed
      between genders, in-hospital mortality rate was higher in females when compared
      with males (6.5% vs. 4.5%; P < 0.001). CONCLUSION: Prompt initiatives should be
      implemented to raise awareness, reduce gender disparities and improve outcomes in
      patients hospitalized with an AMI in Puerto Rico.

PMID- 28496557
TI  - In-Stent Restenosis due to Stent Recoil After Third-Generation Drug-Eluting Stent
      Implantation.
AB  - A 72-year-old man with a heavily calcified coronary lesion underwent percutaneous
      coronary intervention (PCI) using a third-generation drug-eluting stent (DES)
      with thin stent struts. Two months after the PCI, in-stent restenosis due to
      stent recoil (SR) occurred. An intravascular ultrasound (IVUS) revealed deformed
      stent struts and heavily calcified coronary plaque. The SR probably occurred due
      to persistent vessel compression as a result of heavily calcified coronary
      plaque. We should consider using a DES with thick stent struts rather than a
      third-generation DES with thin stent struts in patients with a heavily calcified
      coronary lesion.

PMID- 28496558
TI  - Using the Native Afferent Nervous System to Sense Bladder Fullness: State of the
      Art.
AB  - The regulation of micturition involves complex neurophysiologic pathways, and its
      understanding has grown immensely over the past decade. Alternative approaches
      and applied technologies in the treatment of bladder dysfunction have minimized
      the complications that result from neurogenic bladder. The use of natural bladder
      mechanoreceptors and electroneneurographic (ENG) signal recordings from afferent
      nerves to chronically monitor bladder volume is a promising concept, but the
      technology to accomplish this has proven to be a great biomedical engineering
      challenge. The focus of this paper will be to describe the current state of ENG
      signal recording as a method to detect bladder fullness.

PMID- 28496559
TI  - Harvest of Hope: The impact of a church garden project on African American youth
      and adults in the rural American South.
AB  - A pilot study was conducted of the feasibility of a church garden program to
      impact health outcomes in rural African American youth and adults. Thirty-six
      workdays were held at a Black church. Pre and post-intervention attitudes, diet,
      weight and blood pressure were measured. T-tests were used to test for
      significant within group differences. Spearman's rank correlation coefficients
      were used to test for significant bivariate associations. Youth showed improved
      attitudes about farming and gardening. No statistically significant changes were
      observed in adults. Church garden interventions can improve farming and gardening
      attitudes for rural, African American youth.

PMID- 28496560
TI  - Transmodal Learning of Functional Networks for Alzheimer's Disease Prediction.
AB  - Functional connectivity describes neural activity from resting-state functional
      magnetic resonance imaging (rs-fMRI). This noninvasive modality is a promising
      imaging biomarker of neurodegenerative diseases, such as Alzheimer's disease
      (AD), where the connectome can be an indicator to assess and to understand the
      pathology. However, it only provides noisy measurements of brain activity. As a
      consequence, it has shown fairly limited discrimination power on clinical groups.
      So far, the reference functional marker of AD is the fluorodeoxyglucose positron
      emission tomography (FDG-PET). It gives a reliable quantification of metabolic
      activity, but it is costly and invasive. Here, our goal is to analyze AD
      populations solely based on rs-fMRI, as functional connectivity is correlated to
      metabolism. We introduce transmodal learning: leveraging a prior from one
      modality to improve results of another modality on different subjects. A
      metabolic prior is learned from an independent FDG-PET dataset to improve
      functional connectivity-based prediction of AD. The prior acts as a
      regularization of connectivity learning and improves the estimation of
      discriminative patterns from distinct rs-fMRI datasets. Our approach is a two
      stage classification strategy that combines several seed-based connectivity maps
      to cover a large number of functional networks that identify AD physiopathology.
      Experimental results show that our transmodal approach increases classification
      accuracy compared to pure rs-fMRI approaches, without resorting to additional
      invasive acquisitions. The method successfully recovers brain regions known to be
      impacted by the disease.

PMID- 28496561
TI  - Effects of Disasters on Smoking and Relapse: An Exploratory Study of Hurricane
      Katrina Victims.
AB  - BACKGROUND: Psychosocial stress maintains cigarette use and precipitates relapse,
      but little is known about how natural disasters in particular affect smoking.
      PURPOSE: To determine the feasibility of recruiting victims soon after a natural
      disaster for a survey study, and to assess the types and determinants of changes
      in smoking behavior resulting from exposure to the disaster. METHODS: A
      convenience sample of 35 Hurricane Katrina refugees who had smoked more than 100
      cigarettes in their lifetime were surveyed one month after the storm to evaluate
      changes in smoking behavior. RESULTS: Among a small sample of former smokers,
      more than half relapsed after Katrina, citing stress, urge, and sadness. Among
      current smokers, 52% increased their smoking after Katrina by more than half a
      pack per day on average. Most individuals who increased their smoking or relapsed
      expressed interest in receiving cessation assistance within the next month.
      DISCUSSION: Stress-related increases in smoking and relapse may be common after a
      natural disaster. TRANSLATION TO HEALTH EDUCATION PRACTICE: Health education
      professionals have an important role to play in responding to changes in tobacco
      use in the aftermath of disasters. Educational interventions to discourage
      tobacco use as a coping strategy may be especially warranted given the high level
      of interest expressed in smoking cessation.

PMID- 28496562
TI  - Epigenetics of Lipid Phenotypes.
AB  - Dyslipidemia is a well-established risk factor for cardiovascular disease, the
      main cause of death worldwide. Blood lipid profiles are patterned by both genetic
      and environmental factors. In recent years, epigenetics has emerged as a paradigm
      that unifies these influences. In this review, we have summarized the latest
      evidence implicating epigenetic mechanisms-DNA methylation, histone modification,
      and regulation by RNAs-in lipid homeostasis. Key findings have emerged in a
      number of novel epigenetic loci located in biologically plausible genes (e.g.
      CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from
      animal and cell culture models suggests a complex interplay between different
      classes of epigenetic processes in the lipid-related genomic regions. While
      epigenetic findings hold the potential to explain the interindividual variability
      in lipid profiles as well as the underlying mechanisms, they have yet to be
      translated into effective therapies for dyslipidemia.

PMID- 28496563
TI  - Facilitators and Barriers to HIV Status Disclosure Among HIV-positive MSM Age 50
      and Older.
AB  - OBJECTIVE: Most HIV-positive men who have sex with men (MSM) ages 50 and older
      feel a responsibility to protect their sex partners from HIV transmission risk.
      For some, this is enacted through HIV disclosure, for others, this is realized
      through reduced risk behaviors. METHODS: To examine this, we analyzed interviews
      of 23 HIV-positive MSM ages 50 and older. RESULTS: We identified several
      contextual, relational, and psychosocial factors that served as either barriers
      or facilitators to HIV disclosure. CONCLUSIONS: Our findings suggest HIV status
      disclosure is multifaceted and continues to impact sexual communication in the
      lives of MSM as they enter middle age.

PMID- 28496564
TI  - In-flight allergic emergencies.
AB  - Allergic and hypersensitivity reactions such as anaphylaxis and asthma
      exacerbations may occur during air travel. Although the exact incidence of in
      flight asthma and allergic emergencies is not known, we have concerns that this
      subject has not received the attention it warrants. There is a need to provide
      passengers at risk and airlines with the necessary measures to prevent and manage
      these emergencies. A review of the epidemiology, management and approaches to
      prevention of allergic and asthma emergencies during air travel is presented with
      the goal of increasing awareness about these important, potentially preventable
      medical events.

PMID- 28496565
TI  - An Improved QT Correction Method for use in Atrial Fibrillation and a Comparison
      with the Assessment of QT in Sinus Rhythm.
AB  - BACKGROUND: Conventional QT corrections may be inappropriate inatrial
      fibrillation (AF) due to RR variability and QT lag. Existing formulashave been
      modified by the formula RRmod to account for this lag. Wedeveloped a novel
      correction formula for use in AF (QTAF) based onthe slope ?QT/?RRmod and report
      its performance in AF.We also compare QTAF obtained in AF with rate
      independentcorrections in NSR. MATERIALS AND METHODS: A total of 3063 RR/QT pairs
      from 28 patients with AFwere measured, 22 of whom also had measurements during
      sinus rhythm. QTc (theBazett equation), QTLC (the Framingham linear correction),
      and QTAFwere calculated utilizing RRmod, and the rate-independence of eachformula
      in AF tested. Mean QTAF values in AF were compared to QTintervals corrected with
      QTLC in normal sinus rhythm. RESULTS: ?QTc/?RRmod and?QTLC/?RRmod slopes were
      significantlynon-zero whereas ?QTAF/?RRmod was not. QTLCand QTc corrections were
      imperfect at extremes of RRmod whileQTAF was constant. QTAF corrections in AF
      were shorterthan QTc or QTLC corrections in NSR. CONCLUSIONS: QTAF is a novel QT
      correction with adefined relationship to correction in NSR that performs better
      than existingstrategies.

PMID- 28496566
TI  - Transesophageal Echocardiographyfor Detection Of Left Atrial Appendage Thrombi:
      Is It Good Enough?

PMID- 28496567
TI  - Classification, Etiology and Clinical Evaluation of Atrial Fibrillation.

PMID- 28496568
TI  - Surgical Treatment of Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is now commonly treated at the time of valvular heart
      surgery or coronary artery bypass grafting. Surgical ablation of AF, which is
      predicated upon the Maze procedure, includes creation of lines of conduction
      block and excision of the left atrial appendage. A full bi-atrial lesion set is
      associated with success in 80% to 95% of patients and virtually eliminates the
      risk of late stroke. A complex but safe operation, the classic cut-and-sew Maze
      procedure has been applied by relatively few surgeons. However, recent advances
      in understanding of the pathogenesis of AF and development of new ablation
      technologies enable surgeons to perform pulmonary vein isolation, create linear
      left and right atrial lesions, and remove the left atrial appendage rapidly and
      safely. Lesions are created under direct vision, minimizing the risk of damage to
      the pulmonary veins and adjacent mediastinal structures. Recently developed
      instrumentation now enables thoracoscopic and keyhole approaches, facilitating
      extension of epicardial AF ablation and excision of the left atrial appendage to
      patients with isolated AF and no other indication for cardiac surgery. In
      addition, novel devices designed specifically for minimally invasive epicardial
      exclusion of the left atrial appendage will broaden the range of treatment
      options for patients with AF, possibly eliminating the need for anticoagulation
      in selected patients.

PMID- 28496570
TI  - Preparing The Electrophysiology Lab to Treat Atrial Fibrillation.

PMID- 28496569
TI  - Rate Versus Rhythm Control Pharmacotherapy For Atrial Fibrillation: Where are We
      in 2008?
AB  - Atrial fibrillation (AF) is the most common sustainedcardiac rhythm disturbance
      encountered by physicians. The management of AF isfocused on control of heart
      rate, correction of rhythm disturbance, andrisk-determined prophylaxis of
      thromboembolism. The goals of AF therapy are, aswith other serious disorders, to
      reduce mortality (if possible) and morbidity(improve quality of life, [QOL]). To
      this end, several large studies haveexamined rhythm-control versus rate-control
      strategies. Although a survivaladvantage to using rhythm control with currently
      available antiarrhythmic drugshas not been proven, neither has there been a
      significant excess risk versusrate control. Therefore, using our current
      therapies, the results have notsupported rate control or rhythm control as being
      a preferable first-linetherapy for AF as regards survival; importantly, neither
      do they disprove the hypothesis thatmaintenance of sinus rhythm is preferable to
      the continuation of AF,particularly if rate control fails to restore adequate
      QOL. Many post-hocanalyses and substudies have assessed QOL, functional status,
      and exercisetolerance, with the majority demonstrating important benefits
      associated withachievement of rhythm control. This review examines rate and
      rhythm controloptions, the clinical outcomes of several important AF trials,
      discusses thelimitations in applying the major morbidity/mortality findings to
      everydayclinical practice, and summarizes the lessons learned.

PMID- 28496571
TI  - Characterization of Left Atrial Tachyarrhythmias in Patients Following Atrial
      Fibrillation Ablation:Correlation of surface ECG with Intracardiac Mapping.
AB  - With expected success rates in excess of 80% for achieving long term arrhythmia
      control, catheter based ablation has become a popular treatment strategy in the
      management of patients with atrial fibrillation (AF). However, the success of AF
      ablation has been tempered by the occurrence of post procedure left atrial
      tachycardias and / or flutters, which can be seen in up to 30% of the patients.
      These arrhythmias are perpetuated either due to abnormalities of impulse
      formation (abnormal automaticity / triggered activity), or abnormalities of
      impulse conduction (micro / macroreentry). Regardless of the underlying
      mechanism, these tachycardias manifest distinct "P" or flutter waves on the
      surface ECG, recognition of which may facilitate their characterization /
      localization. However, because of the frequent overlap in the morphology of P
      waves, intracardiac mapping is often the only way to distinguish them apart. This
      is accomplished using a combination of activation, entrainment and
      electroanatomic mapping techniques. Tachycardias resulting from abnormalities of
      impulse formation and / or microreentry are characteristically focal and usually
      confined in and around pulmonary vein (PV) segments which have reconnected
      (septal aspect of right PVs and anterior aspect of left PVs). In contrast,
      macroreentrant tachycardias manifest a large circuit dimension involving zone(s)
      of slow conduction. These are most commonly seen to occur around the mitral valve
      but can develop in any part of the left atrium where "gaps" across prior ablation
      lesion sets create altered conduction. Successful ablation of focal tachycardias
      is usually accomplished by isolating the reconnected PV segment(s). In case of
      macroreentrant arrhythmias however, a more extensive ablation approach is
      typically required in order to achieve conduction block across isthmus of the
      circuit. Using these strategies, the majority of left atrial tachycardias
      occurring post AF ablation can be successfully cured with excellent long term
      results.

PMID- 28496573
TI  - Antiarrhythmic Effect of Statin Therapy and Atrial Fibrillation A Meta-Analysis
      of Randomized Controlled Trials.
AB  - The aim of this meta-analysis was to improve the evaluation of the possible
      antiarrhythmic effect of statins on atrial fibrillation (AF) incidence
      orrecurrence.

PMID- 28496572
TI  - Success of Radiofrequency Catheter Ablation of Atrial Fibrillation: Does Obesity
      Influence the Outcomes?
AB  - Background: Catheter ablation of atrial fibrillation (AF) is an increasingly
      popular therapeutic option for symptomatic patients who have failed multiple
      antiarrhythmic drugs (AADs). Patients of higher body mass index often fail direct
      current cardioversion. The role of body mass index (BMI) on the success of AF
      ablation is not well understood. Methods: We prospectively studied 511 patients
      who underwent AF ablation at the Cleveland Clinic Foundation between 2002 and
      2005. Patients were divided into four classes based on their BMI: Class I ( 25);
      Class II (25.1-30); Class III (30.1-35) and Class IV (>35). These groups were
      compared for baseline demographic and clinical characteristics. Any recurrence of
      AF after 3 months of ablation was considered as failure. All classes were
      followed for at least 12 months and rates of failure were compared. Results:
      Based on their BMI, 25% of patients were assigned to class I, 37% in class II,
      21% in class III and 16% in class IV. Patients of higher classification (class
      III or IV) were more likely to be male (p<0.001), diabetic (p<0.001), smokers
      (p=0.002), with coronary artery disease (=0.018), left atrial enlargement
      (p=0.015) and longstanding AF (p=0.007). Severity of obesity as measured by BMI
      had a direct correlation to early (p=0.05) and late (p=0.01) recurrence of AF.
      Conclusion: Obesity is significantly associated with long-term AF recurrence
      after catheter ablation. Higher incidence of smoking & left atrial enlargement
      may possibly contribute to higher failure rates in this sub-group of patients.

PMID- 28496574
TI  - Long-Termendurance Sport Practice Increases The Incidence Of Lone Atrial
      Fibrillation Inmen: A Follow-Up Study.

PMID- 28496575
TI  - AF Termination: the Holy Grail of Persistent AF Ablation?

PMID- 28496576
TI  - Pre-Procedural Imaging to Direct Catheter Ablation of Atrial Fibrillation:
      Anatomy and Ablation Strategy.
AB  - Successful catheter ablation of atrial fibrillation (AF) requires a detailed
      understanding of left atrial anatomy in order to maximize the safety and efficacy
      of the procedure. Common and rare variants of left atrial and pulmonary venous
      anatomy have been described which can affect the optimal ablation strategy for
      each individual patient. These variants include the presence of a right or left
      middle pulmonary vein, a left or right common pulmonary vein, a common inferior
      pulmonary vein, a right top pulmonary vein, and other rare forms of anomalous
      pulmonary venous drainage. There are also important patient-specific differences
      in pulmonary venous ridges and left atrial roof morphology. Pre-procedural CT or
      MR imaging can define these anatomic variants in exquisite detail and be used
      with image-integration strategies to direct the ablation procedure. In this
      review, we describe common and uncommon variants that can be identified by pre
      procedural imaging, and suggest ablation strategies tailored to these anatomic
      variants.

PMID- 28496577
TI  - Trigger Versus Substrate Ablation for Atrial Fibrillation.
AB  - Elimination of triggers has become the hallmark of catheter ablation of atrial
      fibrillation (AF). In particular, much attention has been paid to the elimination
      of triggering impulses from the pulmonary veins via pulmonary vein ablation
      procedures. While this approach has a proven track record for paroxysmal AF, the
      efficacy in non-paroxysmal AF has been less convincing. Thus, attention has been
      paid to elimination of the substrate responsible for AF perpetuation, including
      complex fractionated electrograms, dominant frequency sites, and autonomic
      ganglionated plexi. None of these targets has yet become mainstream, but they are
      all under active investigation. As our knowledge of these targets increases and
      clinical studies are performed, a more refined approach to AF ablation will
      surely emerge.

PMID- 28496579
TI  - Intracardiac ECHO Integration with Three Dimensional Mapping: Role in AF
      Ablation.
AB  - Background: Catheter ablation of atrial fibrillation (AF) is typically guided by
      3D mapping. This involves point-by-point reconstruction of the 3D virtual anatomy
      and may be time consuming and require substantial fluoroscopy exposure.
      Intracardiac echocardiography (ICE) affords real time imaging of the cardiac
      structures during mapping and ablation. Methods: Between February and May 2007,
      15 patients (100% men, 10 with paroxysmal AF) presenting for AF ablation were
      offered mapping using a novel system integrating 3D mapping and ICE. A modified
      ICE probe with a location sensor tracked by the mapping system was positioned in
      the right atrium (RA). This allowed acquisition of ECG gated images of the left
      atrium (LA). Endocardial contours were traced on each image and were used to
      generate a registered 3D map. Results: 3D maps took a mean of 51+/-25 minutes to
      create, PRIOR to entering the LA and without fluoroscopy. Pulmonary veins and the
      esophagus were rendered in 3D. A complete map was built from a mean of 46+/-19
      contours. Upon instrumentation of the left atrium, the maps were easily distorted
      if points collected by the mapping catheter were combined with the original map,
      due to deformation of the left atrial geometry by the relatively stiff ablation
      catheter. Pulmonary vein antrum isolation was guided by a circular mapping
      catheter. Since this catheter could not be visualized on the CARTO map,
      fluoroscopy was used to track its position and the contact between the ablation
      catheter and the circular mapping catheter. No substantial reduction in
      fluoroscopy time was thus realized, as expected. At 10+/-1 months of followup,
      73% of the patients were in sinus rhythm after the initial three month blanking
      period. No patient suffered any complications related to the procedure or in
      follow-up. Conclusions: A mapping system combining ICE and 3D electroanatomical
      mapping can feasibly reconstruct a 3D shell of the LA and the pulmonary veins
      without the need to enter the left heart. The map created is sensitive to
      distortion during point-by-point mapping with the standard ablation catheter.

PMID- 28496580
TI  - Skin Burn at the Site of Indifferent Electrode after Radiofrequency Catheter
      Ablation of AV Node for Atrial Fibrillation.
AB  - Radiofrequency Ablation of AV node with permanent pacemaker has been used to
      achieve rate control in persistent symptomatic atrial fibrillation. Although RF
      Ablation is safe, complications may occur in up to 3% of the procedures. A rare
      complication of 2nd degree skin burn at indifferent electrode site has been
      described here. This report highlights the rare but possible complication in
      patients undergoing such a procedure and help in preventing by taking appropriate
      measures.

PMID- 28496581
TI  - Is Empirical Four Pulmonary Vein Isolation Necessary for Focally Triggered
      Paroxysmal Atrial Fibrillation? Comparison of Selective Pulmonary Vein Isolation
      Versus Empirical Four Pulmonary Vein Isolation.

PMID- 28496582
TI  - Catheter Ablation for Atrial Fibrillation in Patients with Obesity.

PMID- 28496584
TI  - Design of an Outpatient Atrial Fibrillation of Excellence: Current Experience
      with the Deliver of Pre and Post Procedure Care.

PMID- 28496583
TI  - Atrial Fibrillation and Heart Failure.
AB  - Atrial fibrillation is common in heart failure patients and is associated with
      increased mortality. Pharmacologic trials have not shown any survival benefit for
      a rhythm control over a rate control strategy. It has been suggested that sinus
      rhythm is associated with a survival benefit, but that the risks of anti
      arrhythmic drug treatment and poor efficacy offset the beneficial effect.
      Catheter ablation for atrial fibrillation can establish sinus rhythm without the
      risks of anti-arrhythmic drug therapy. Data from randomized trials demonstrating
      a survival benefit for patients undergoing an ablation procedure for atrial
      fibrillation are still lacking. Ablation of the AV junction and permanent pacing
      remain a treatment alternative in otherwise refractory cases. Placement of a
      biventricular system may prevent or reduce negative consequences of chronic right
      ventricular pacing. Current objectives and options for treatment of atrial
      fibrillation in heart failure patients are reviewed.

PMID- 28496585
TI  - Cardiac Image Registration.
AB  - Long procedure time and somewhat suboptimal results hinder the widespread use of
      catheter ablation of complex arrhythmias such as atrial fibrillation (AF). Due to
      lack of contrast differentiation between the area of interest and surrounding
      structures in a moving organ like heart, there is a lack of proper
      intraprocedural guidance using current imaging techniques for ablation. Cardiac
      image registration is currently under investigation and is in clinical use for AF
      ablation. Cardiac image registration, which involves integration of two images in
      the context of the left atrium (LA), is intermodal, with the acquired image and
      the real-time reference image residing in different image spaces, and involves
      optimization, where one image space is transformed into the other. Unlike rigid
      body registration, cardiac image registration is unique and challenging due to
      cardiac motion during the cardiac cycle and due to respiration. This review
      addresses the basic principles of the emerging technique of registration and the
      inherent limitations as they relate to cardiac imaging and registration.

PMID- 28496586
TI  - Sinus Node Dysfunction in Atrial Fibrillation: Cause or Effect?

PMID- 28496587
TI  - Impact of Smoking on the Atrial Substrate Characteristics in Patients with Atrial
      Fibrillation.

PMID- 28496589
TI  - Echocardiographic Predictors of Symptomatic Atrial Fibrillation In Patients with
      Rheumatic Mitral Stenosis and Normal Sinus Rhythm.
AB  - : Introduction: Rheumatic mitral stenosis (RMS) increases the risk of both atrial
      fibrillation (AF) and thromboembolism. Methods: Patients with mitral stenosis and
      normal sinus rhythm were enrolled in the study prospectively.The present study
      was designed to study whether echocardiographic evaluation in patients with
      mitral stenosis and normal sinus rhythm could predict the occurrence of
      symptomatic AF . RESULTS: Sixty-two patients (51 females) with mitral stenosis
      and normal sinus rhythm were included in the study. Seven patients (11.3%)
      developed symptomatic AF and the remaining 55 were free of AF during a followed
      up of 22+/-5 months. The following echocardiographic parameters were
      significantly increased and predicted the development of AF; left atrial (LA)
      mediolateral diameter (5.5 +/- 0.5 cm vs 4.7 +/- 0.7 cm), right atrial
      mediolateral diameter (4,7 +/- 1.0 cm vs 3.6 +/- 1.3 cm), LA area in the apical
      two chamber view ( 31 +/- 3.2 cm2 vs 25 +/- 5.8 cm2), right atrial volume (52 +/-
      22 cm3 vs 34 +/- 19 cm3), and interatrial conduction time (IACT) (142 +/- 22 msec
      vs 115 +/- 16 msec). Conclusions: This study revealed that echocardiography can
      be used to predict symptomatic AF in patients with RMS and sinus rhythm.

PMID- 28496590
TI  - GIANT Flutter Waves in ECG Lead V1: a Marker of Pulmonary Hypertension.
AB  - Atrial flutter (AFl) may exist with or without underlying structural heart
      disease. Typical AFl presents as a "sawtooth" pattern on the ECG - with inverted
      flutter (F) waves in the inferior leads and upright F waves in V1. This
      morphology offers no direct clues as to the underlying cardiac disorder, if any.
      Occasionally we have encountered giant F waves, most prominently in lead V1,
      reaching 5 mv or more in height - sometimes exceeding the QRS voltage. The
      significance of this pattern has not been investigated and reported on. To
      determine if giant F waves in V1 provide any insight into the
      presence/type/absence of specific underlying cardiac pathology, the history of 6
      consecutive patients with giant F waves was reviewed. Upon review, the only
      factor common to each patient was the presence of or history of pulmonary
      hypertension. Right ventricular dilation and/or dysfunction and right atrial
      enlargement with or without tricuspid insufficiency were present in each by
      echocardiography. Giant F waves appear to occur in the setting of right heart
      dysfunction in patients with a history of or the continued presence of pulmonary
      hypertension. Their detection should indicate the need for right heart
      evaluation.

PMID- 28496588
TI  - Atrial Septal Defect and Atrial Fibrillation: The Known and Unknown.
AB  - Atrial fibrillation (AF) is a common complication in patients with atrial septal
      defects (ASDs). The link between AF and ASD is fairly complex and entails
      modifications in electrophysiologic, contractile and structural properties, at
      the cellular and tissue level, of both atria, mainly due to chronic atrial
      stretch and dilation. Surgical repair or percutaneous closure of ASDs are equally
      effective in reducing mortality and symptoms but limited in preventing or curbing
      AF, unless combined with an arrhythmia-specific procedure. Transesophageal
      echocardiography (TEE) and intracardiac echocardiography (ICE) have improved the
      safety and success of the above procedures. Finally, clearer understanding of the
      pathophysiology of AF in patients with ASD (and CHF, in general) has led to
      target-specific advances in medical management.

PMID- 28496591
TI  - Underutilization of Warfarin Therapy in Elderly Patients with Atrial Fibrillation
      - Fear or False Sense of Security!
AB  - Background: Under utilization of warfarin in elderly patients with atrial
      fibrillation (AF) has been recognized as a significant health care issue. This
      study examines the rate and reasons for warfarin underutilization in elderly
      patients with AF at the Kansas City Veterans Affairs Medical Center. Methods:
      Retrospective study reviewing electronic medical records of all patients aged 65
      and older with the diagnosis of atrial fibrillation. Patients on warfarin were
      excluded. Reasons for not using warfarin were extracted by reviewing the
      electronic medical record. Anticoagulation indications for these patients were
      determined based on the ACC/AHA/ESC 2006 Guidelines for the Management of
      Patients with Atrial Fibrillation. Results: Warfarin was not used by 407 patients
      (25%) with known AF. Average age was 79+6.2 years. 60% of patients had persistent
      or permanent AF. Prevalence of risk factors for thromboembolism included
      hypertension (74%), heart failure or ejection fraction of <40% (21%), diabetes
      (27%) and coronary artery disease (48%). CHADS (2) scores were documented in the
      charts less than 1% of the times. Only 11 patients had CHADS (2) score of 0 and
      70 had a score of 1. A class I or IIa indication for warfarin therapy was present
      in 298 (73%) of patients. Return to sinus rhythm (37%) was the most common reason
      for not using warfarin. In 30% of cases the reason not to use warfarin was not
      addressed. Other reasons not to use warfarin included fear of falls (7%), prior
      head or GI bleed (14%), patient refusal & noncompliance (12%). History of CVA or
      TIA was documented in 12% of patients. Conclusions: Underutilization of warfarin
      in elderly patients with atrial fibrillation remains a common problem despite
      their high risk for thromboembolic events. A false sense of security about the
      paroxysmal nature of AF, lack of proper insight about stroke risk (CHADS (2)),
      and fear of bleeding are the most common reasons for non use of warfarin.

PMID- 28496592
TI  - Physical Activity and Incidence of Atrial Fibrillation in Older Adults: The
      Cardiovascular Health Study.

PMID- 28496593
TI  - Left Atrial Image Registration to Guide Catheter Ablation of Atrial Fibrillation:
      In the Eye of the Technology.

PMID- 28496594
TI  - Periablative Anticoagulation Strategies in Patients with Atrial Fibrillation.
AB  - Atrial fibrillation is associated with thromboembolic events that may cause
      important impairment on quality of life. Pulmonary vein isolation is the
      treatment of choice in cases that are refractory to medical therapy. Once sheaths
      and catheters are manipulated inside the left atrium, anticoagulation with
      heparin must be used during the procedure to protect patients from thromboembolic
      phenomena. Different strategies of anticoagulation are used at different centers.
      This review summarizes the pathophysiology of thrombus formation in the left
      atrium, defines which patients are under high risk and describes the main
      strategies used for anticoagulation.

PMID- 28496595
TI  - Catheter Abalation for AF : Past, Present and Future.

PMID- 28496596
TI  - Leukocyte-Aprotinin Atrial Fibrillation Study (LAFFS): Impact of Aprotinin and
      Leukofiltration on Atrial Fibrillation, Renal Insufficiency and Encephalopathy
      Post-Cardiopulmonary Bypass.
AB  - Purpose: Atrial fibrillation remains the leading postoperative complication
      following cardiopulmonary bypass. A randomized trial was undertaken to evaluate
      the effectiveness of leukocyte filtration and aprotinin, applied separately and
      in combination, on the incidence of post-operative atrial fibrillation. A
      secondary component of the study was the impact of these adjunct interventions on
      post-surgical renal and neurological dysfunction. Methods: A total of 1,220
      patients undergoing primary isolated coronary artery bypass grafting were
      randomly assigned to one of four treatment groups. The control group (305
      patients) received standard cardiopulmonary bypass with moderately hypothermic
      (34oC) cardioplegic arrest. In the filtration group (310 patients) leukocyte
      reducing filters were incorporated into the bypass circuit and deployed
      strategically. The aprotinin group (285 patients) received full Hammersmith dose
      aprotinin. The combination therapy group (320 patients) received both aprotinin
      and leukocyte filtration. Results: The incidences of atrial fibrillation were 25%
      in the control group, 16% in the filtration group, 19% in the aprotinin group and
      10% in the combination therapy group (P < 0.001). Renal dysfunction was detected
      in 3% of the control group, 2% of the filtration group, 8% of the aprotinin
      group, and 5% of the combination group (P < 0.005). Neurological dysfunction
      occurred in 2% of the control group, 2% of the filtration group, 1% of the
      aprotinin group, and 2% of the combination group (P = n.s.). Conclusions:
      Combination therapy with aprotinin and leukocyte filtration markedly reduced
      atrial fibrillation post-cardiopulmonary bypass, and was more effective than the
      individual treatments. Aprotinin treatment increased the incidence of renal
      dysfunction, and the addition of leukocyte filtration partially mitigated this
      detrimental effect of aprotinin. Thus, strategic leukocyte filtration augments
      aprotinin's anti-arrhythmic effects while suppressing its nephrotoxic sequelae.

PMID- 28496597
TI  - Typical Flutter Ablation as an Adjunct to Catheter Ablation of Atrial
      Fibrillation.
AB  - During the past decades there has been a consistent evolution of both surgical
      and catheter-based techniques for the treatment of stand-alone atrial
      fibrillation, as alternatives or in combination with anti-arrhythmic drugs.
      Transcatheter ablation has significantly improved outcomes, despite often
      requiring multiple procedures and with limited success rates especially in
      presence of persistent atrial fibrillation. Surgical procedures have dramatically
      evolved from the original cut-and-sew Maze operation, allowing nowadays for
      closed-chest epicardial ablations on the beating heart. Recently, the concept of
      a close collaboration between the cardiac surgeon and the electrophysiologist has
      emerged as an intriguing option in order to overcome the drawbacks and suboptimal
      results of both techniques; therefore, the hybrid approach has been proposed as a
      potentially more successful strategy, allowing for a patient-tailored
      therapeutical approach. We reviewed the recent advancements either from the
      transcatheter and surgical standpoint, with a peculiar focus on the current
      option to merge both techniques along with an up-to-date review of the
      preliminary clinical experiences with the hybrid, surgical-transcatheter
      treatment of stand-alone atrial fibrillation.

PMID- 28496598
TI  - Extra Atrial Disease in Patients with "Lone" Atrial Fibrillation.
AB  - AIMS: Lone atrial fibrillation (LAF) is considered by some to be a primary atrial
      electrophysiologic disorder. However, we have frequently observed evidence of
      "extraatrial" diseases - atherosclerosis and associated metabolic disorders - in
      our LAF patients. We sought to characterize and quantify extraatrial disease
      burden in LAF patients, and to correlate this burden with features of the
      arrhythmia including pattern (paroxysmal versus persistent) and response to
      catheter ablation. METHODS AND RESULTS: Forty-six consecutive patients with non
      familial LAF underwent assessment for evidence of atherosclerosis (computed
      tomographic vascular calcification and elevated arterial pulse wave velocity) and
      associated metabolic diseases (dyslipidemia, insulin resistance and
      inflammation), and then catheter ablation. The cohort had a significant incidence
      of atherosclerosis (57%) and metabolic (70%) diseases. Patients with persistent
      AF tended to have a greater extraatrial disease burden than those with paroxysmal
      AF. A significant inverse relationship between the rate of ablation success and
      extraatrial disease burden was demonstrated. CONCLUSIONS: Extraatrial disease was
      common in this LAF cohort. Correlations between extraatrial disease burden and
      features of the arrhythmia would, if verified, challenge the notion that LAF is a
      "primary" electrophysiologic disorder.

PMID- 28496599
TI  - The Anticoagulated Atrial Fibrillation Patient Who Requires "Curative" Therapy
      for Prostate Carcinoma: a Bleeding Conundrum.

PMID- 28496600
TI  - Role of the Auotnomic Nerves system in the Creation of Substrate for Atrial
      Fibrillation.

PMID- 28496601
TI  - Quality of Life, Exercise Capacity and Comorbidity in Old Patients with Permanent
      Atrial Fibrillation.
AB  - : Background: The impact of atrial fibrillation (AF) on quality of life (QoL)
      differs with the AF population studied and is influenced by comorbidity. In
      hospital-based studies younger and highly symptomatic patients may be
      overrepresented. We performed an observational cross sectional study in two
      municipalities, comparing 75 year-old patients with and without permanent atrial
      fibrillation, with respect to health-related QoL and exercise capacity, with
      adjustment for the effects of confounders. Methods: Maximal treadmill exercise
      testing provided peak oxygen uptake (VO2 peak). Health-related QoL was assessed
      by self-completed SF-36 questionnaires. The lowest quartile identified poor
      outcomes. RESULTS: 27 subjects with permanent AF and 71 subjects in sinus rhythm
      participated. AF patients had higher prevalence of compensated chronic heart
      failure (p < 0.001), valvular heart disease (p < 0.001), lower mean VO2 peak
      (22.7 +/- 5.5 vs. 28.6 +/- 6.3 ml/kg/min; p < 0.001), and more often poor VO2
      peak; crude OR 5.3 (95%CI 1.8, 15.3), adjusted OR 7.5 (2.0, 28.3). Median
      Physical Component Summary score (with 25th and 75th percentile) was 41 (31, 51)
      in AF vs. 52 (45, 55) in controls (p < 0.001). Furthermore, the AF group had
      higher odds for poor physical QoL scores; crude OR 5.0 (1.8, 13.7), adjusted OR
      4.3 (1.5, 12.4). Median Mental Component Summary score was 56 (42, 61) in the AF
      group vs. 57 (51, 60) in controls (p=0.565). The AF group had non-significantly
      increased odds for poor mental QoL scores; crude OR 2.3 (0.8, 6.2), adjusted OR
      2.8 (1.0, 8.4). Conclusion: Also after adjustment for confounders, older patients
      with permanent AF had higher odds for poor exercise capacity and poor physical
      QoL compared to subjects in sinus rhythm.

PMID- 28496602
TI  - The A That Did Not Fib:Two Roads Both Traveled By.
AB  - Case: A 64-year-old woman presented with palpitations. Her 24-hour Holter monitor
      revealed runs of presumed atrial fibrillation (AF). The patient was referred for
      EP study and AF ablation. EPS: At EPS, an anterograde A-H jump was noted.
      Spontaneous bursts of tachycardia were seen, consisting of sinus atrial beats
      with dual ventricular responses, each preceded by a His deflection. There was no
      atrial fibrillation during the study. Radiofrequency ablation of the slow AV node
      pathway was performed. There were no inducible tachycardias and no A-H jump
      following the ablation. The patient had no recurrence post-procedure. Discussion:
      This case presents a rare example of simultaneous dual anterograde AV-nodal
      conduction. The conditions leading to this phenomenon include dual AVN pathways,
      markedly slowed conduction in the slow pathway, and lack of retrograde conduction
      up either pathway such that reentry was impossible. An irregular, narrow-complex
      tachycardia resulted, initially interpreted as AF. Slow-pathway ablation was
      curative.

PMID- 28496603
TI  - Atrial Fibrillation: a Patient's Guide to Understanding Drug Therapy.

PMID- 28496604
TI  - Do Statins Decrease the Arrhythmia Burden in Patients with Paroxysmal Atrial
      Fibrillation?

PMID- 28496605
TI  - Is Rhythm Control with Pulmonary Vein Isolation Superior to Rate Control with AV
      Nodal Ablation in Patients with Heart Failure?

PMID- 28496606
TI  - Are Balloon Based Strategies Better Than Conventional Radiofrequency Catheter
      Ablation: Exploring New Frontiers In The Treatment Of Atrial Fibrillation.
AB  - Paroxysmal atrial fibrillation can be eliminated with continuous circular linear
      lesions around the pulmonary veins using radiofrequency ablation. Due to the
      technical complexity of this procedure balloon-based devices have been developed
      to simplify pulmonary vein isolation. Cryoballoon ablation provides excellent
      safety and is technically less demanding when compared to radiofrequency catheter
      ablation in selected patients. In this review, advantages as well as drawbacks of
      this emerging technology in relation to standard catheter ablation are discussed.

PMID- 28496607
TI  - QT Prolongation Following Ectopic Beats: Initial Data Regarding The Upper Limit
      Of Normal With Possible Implications For Antiarrhythmic Therapy And Concealed
      (Unexpressed) Long QT.
AB  - : Background: Ectopic beats are frequently associated with morphologic
      repolarization alterations of ensuing sinus beats. Less is known about
      repolarization duration alterations of post-ectopic sinus beats. In one patient
      who developed long QT and torsades de pointes upon exposure to a class III
      antiarrhythmic drug, and was later genotyped as being a carrier for long QT
      syndrome (LQTS) type 1, review of a pre-drug Holter monitor study revealed marked
      QT prolongation of post-ectopic sinus beats. In wondering whether this might be a
      common clue to "concealed" unexpressed LQTS, we realized that we must first
      characterize the range of post-ectopic QT prolongation present in normals.
      Prolongation beyond the upper limit of this range might then raise suspicion of
      possible LQTS and alter the antiarrhythmic drug selection process for the
      suppression of atrial fibrillation or other arrhythmias. Methods: Accordingly, we
      assessed the presence/degree of repolarization prolongation following premature
      ectopic impulses in 166 subjects with normal conduction intervals and normal
      repolarization on their resting 12-lead ECG, 75 of whom had no known associated
      cardiovascular disorder of any kind. That is, in our subjects, the maximal
      prolongation of the QT interval of the sinus beat following isolated ventricular
      and atrial premature complexes was characterized. Results: QT prolongation is
      common in post ectopic sinus beats. However, in our subjects the uncorrected QT
      interval of post-ectopic sinus beats never exceeded 480 ms in duration [which was
      much shorter than that seen (510-590 ms) in our gene carrier]. CONCLUSIONS: The
      QT interval in normal subjects may prolong following premature complexes but not
      to a value in excess of 480 ms.

PMID- 28496608
TI  - Atrial Fibrillation And Coronary Heart Disease:Fatal Attraction.
AB  - In this manuscript, the profile and clinical management of hypertensive patients
      with chronic ischemic heart disease and atrial fibrillation (AF) is examined and
      whether high heart rate is associated with a different profile is determined.
      CINHTIA was a cross-sectional and multicenter survey aimed to define the clinical
      profile of hypertensive patients with chronic ischemic heart disease daily
      attended in Spain. Blood pressure, LDL-cholesterol and diabetes control rates
      were established according to ESHESC 2003, NCEP-ATP III and ADA 2005 guidelines,
      respectively. Out of the 2024 patients, 338 (16.7%) exhibited AF. The group of
      patients with AF was older and with higher prevalence of diabetes, organ damage
      and cardiovascular disease. Blood pressure (41.8% vs 34.5%, p=0.014) and diabetes
      (28.5% vs 20.9%,p=0.044) were worse controlled in patients with AF, with a trend
      to a lower control of LDL-cholesterol (31.2% vs 26.8%, p=0.093). When
      distributing patients with AF according to heart rate, except for smoking, left
      ventricular hypertrophy and peripheral arterial disease that were more frequent
      in those with higher heart rate, no significant differences were found in other
      risk factors or organ damage between groups. Blood pressure, glycemia and LDL
      cholesterol were worse controlled in the subgroup with highest heart rate. In
      clinical practice, hypertensive patients with chronic ischemic heart disease and
      AF have a bad prognosis not only due to a worse clinical profile, but also due to
      lower risk factors control rates. In contrast with patients at sinus rhythm,
      higher heart rate was less related with a worse clinical profile in subjects with
      AF.

PMID- 28496609
TI  - Anticoagulation During AF Ablation: The Balance between Thromboembolism and
      Bleeding.
AB  - Radiofrequency ablation for atrial fibrillation is being increasingly used to
      treat patients with symptomatic arrhythmia. The procedure is complex and
      associated with significant complications including thromboembolism, stroke, and
      bleeding. Despite significant advances in catheter design, online cardiac
      imaging, and greater operator experience, both stroke and major vascular
      complications continue to be problematic. Increasing the duration and intensity
      of anticoagulation has been the primary modality used to decrease
      thromboembolism. However, these measures increase the likelihood and severity of
      bleeding-related complications. The optimal method of anticoagulation along with
      the adjunctive use of technology to decrease vascular complications and
      mechanically prevent cerebral embolization is unknown. In this paper, we review
      the present methods used by ablationists to decrease the likelihood of
      thromboembolism during atrial fibrillation. We then describe methods used to
      decrease bleeding and vascular complications at access sites as well as cardiac
      perforation. We briefly discuss newer techniques to decrease endovascular
      complications including epicardial ablation and the use of temporarily implanted
      vascular protection devices.Finally, we describe the best option or combination
      of approaches that attempt to balance the risks of thromboembolism and bleeding
      during AF ablation..

PMID- 28496610
TI  - Presence Of Left Atrial Appendage Thrombus In Patients Presenting For Left Atrial
      Ablation Of Atrial Fibrillation Despite Pre-Operative Anticoagulation.
AB  - Background: One of the recognised complications of left atrial ablation for
      atrial fibrillation (AF) is stroke. Left atrial (LA) thrombus, which may be
      dislodged by catheter manipulation, is an absolute contraindication to ablation.
      It is unclear whether imaging of the left atrial appendage (LAA) by
      transesophageal echo (TEE) is mandatory to exclude LA clot prior to ablation,
      particularly in "low-risk" patients with paroxysmal AF and normal left
      ventricular (LV) function. Methods and Results: We carried out a retrospective
      analysis of pre-ablation TEE in patients presenting for ablation of AF. Images
      from 244 ablation procedures carried out in 148 patients were examined, including
      106 patients with paroxysmal AF and normal LV function. Despite at least 4 weeks
      of pre-operative therapeutic anticoagulation with Warfarin (INR>2.0), LAA
      thrombus was identified in 4 patients (2.7% (0.1-5.3%)). These included 2
      patients with paroxysmal AF and normal LV function, although both had a high
      arrhythmia burden. The thrombi regressed with intensification of anticoagulation.
      Conclusions: Pre-operative imaging of the LAA remains advisable to exclude
      thrombus prior to ablation for AF even in patients with paroxysmal AF and normal
      LV function, especially if there is a high AF burden.

PMID- 28496611
TI  - Atrial Fibrillation Progression: New Insight in TheNatural History of This
      Arrhythmia.

PMID- 28496612
TI  - Review on "High-Density Mapping of Atrial Fibrillation in Humans: Relationship
      Between High-Frequency Activation and Electrogram Fractionation".

PMID- 28496613
TI  - 14th Annual Boston Atrial Fibrillation Symposium Proceedings - Technology Round
      Up.

PMID- 28496614
TI  - Cardiovascular Risk Factors and Atrial Fibrillation: What is the Link?

PMID- 28496615
TI  - Accurate Detection Of Left Atrial Thrombus Prior To Atrial Fibrillation Ablation
      In Patients With Therapeutic Anticoagulation: Does Transesophageal
      Echocardiography Beat Conventional Wisdom?

PMID- 28496616
TI  - Genetics and Sinus Node Dysfunction.

PMID- 28496618
TI  - Predictors of Success After a First Circumferential Pulmonary Vein Isolation For
      Atrial Fibrillation.
AB  - Background: To identify and characterise pre-procedural and procedural parameters
      which predict maintenance of sinus rhythm after a first circumferential pulmonary
      vein isolation (CPVI) for recurrent atrial fibrillation (AF). Methods: 100
      patients (54+/-10 yrs) undergoing CARTO-guided CPVI for symptomatic drug
      refractory, paroxysmal or shortstanding persistent AF were studied. The endpoint
      was complete electrical isolation within the encircled regions. 3D left atrial
      (LA) volume was measured by CARTO geometry. Follow-up examinations (symptoms,
      ECG, 24-hour ECG recording) were performed at 1 and 3 months and every 3 months
      thereafter. Results: After the first CPVI, 71 patients (71%) were free of AF
      without antiarrhythmic drug therapy (follow up:28+/-11 months). The only
      independent and significant predictors for freedom of AF after the first CPVI
      were duration of AF history and 3D LA volume (p<0.05). However, a significant
      overlap in durations of AF history and 3D LA volumes between failures and
      successes was observed. Conclusions: (1) Using the "circumferential pulmonary
      vein isolation" approach, the first catheter ablation leads to resolution of
      arrhythmia in ~ 70% of symptomatic AF patients. (2) Independent predictors for
      freedom of AF after initial CPVI are duration of AF history and 3D LA volume. (3)
      Due to considerable overlap between failures and successes, these parameters can
      not be used to identify patients who should not undergo CPVI or in whom an
      additional ablation beyond CPVI is required. On the other hand, our results do
      suggest that an ablation strategy early in the course of AF disease can influence
      successful outcome.

PMID- 28496619
TI  - Is Cryo a Better Energy Source Than Radiofrequency for AF Ablation in Preventing
      Esophageal Injury?

PMID- 28496620
TI  - Ectopic Triggers of Superior Vena Cava in Atrial Fibrillation.

PMID- 28496621
TI  - Scenes from a CFAE: Complex Fractionated Atrial Electrogram Map in a Woman with
      Longstanding Persistent Atrial Fibrillation Following Mechanical Mitral Valve
      Replacement.
AB  - Case: A 62-year-old woman was referred for atrial fibrillation (AF) ablation. She
      had longstanding persistent AF for 8 years since mechanical mitral valve
      replacement for rheumatic heart disease. EPS: A strategy of substrate-based
      ablation targeting areas of complex fractionated atrial electrograms (CFAE) was
      pursued. These sites were identified by inspection of electrograms and verified
      with software-based electrogram analysis, with the left atrial roof demonstrating
      the highest density of CFAE sites. Successful catheter ablation was performed.
      The patient has remained free of recurrence over 4 months of follow-up.
      Discussion: This case presents a successful ablation procedure using the emerging
      strategy of CFAE-targeted ablative lesions. Given the patient's longstanding
      persistent AF and mechanical mitral valve, the high density of CFAE sites on the
      left atrial roof was an unexpected finding. Analysis for CFAE sites guided the
      procedure in a direction that might otherwise not have been undertaken, leading
      to a successful ablation.

PMID- 28496617
TI  - Atrial Fibrillation: The New Epidemic of the Ageing World.
AB  - The prevalence of atrial fibrillation (AF) increases with age. As the population
      ages, the burden of AF increases. AF is associated with an increased incidence of
      mortality, stroke, and coronary events compared to sinus rhythm. AF with a rapid
      ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct
      current (DC) cardioversion should be performed in patients with AF and acute
      myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe
      heart failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may
      be administered to reduce immediately a very rapid ventricular rate in AF. An
      oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a
      fast ventricular rate occurs at rest or during exercise despite digoxin.
      Amiodarone may be used in selected patients with symptomatic life-threatening AF
      refractory to other drugs. Digoxin should not be used to treat patients with
      paroxysmal AF. Nondrug therapies should be performed in patients with symptomatic
      AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF
      associated with the tachycardia-bradycardia syndrome should be treated with a
      permanent pacemaker in combination with drugs. A permanent pacemaker should be
      implanted in patients with AF and symptoms such as dizziness or syncope
      associated with ventricular pauses greater than 3 seconds which are not drug
      induced. Elective DC cardioversion has a higher success rate and a lower
      incidence of cardiac adverse effects than does medical cardioversion in
      converting AF to sinus rhythm. Unless transesophageal echocardiography has shown
      no thrombus in the left atrial appendage before cardioversion, oral warfarin
      should be given for 3 weeks before elective DC or drug cardioversion of AF and
      continued for at least 4 weeks after maintenance of sinus rhythm. Many
      cardiologists prefer, especially in elderly patients , ventricular rate control
      plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs.
      Patients with chronic or paroxysmal AF at high risk for stroke should be treated
      with long-term warfarin to achieve an International Normalized Ratio of 2.0 to
      3.0. Patients with AF at low risk for stroke or with contraindications to
      warfarin should be treated with aspirin 325 mg daily.

PMID- 28496623
TI  - JAFIB : A Comprehensive Resource for Afib ....

PMID- 28496622
TI  - Biatrial, 3-Dimensional Mapping of Human Atrial Fibrillation: Methodology and
      Clinical Observations.

PMID- 28496624
TI  - Assessing Patient Management and Outcomes in Atrial Fibrillation: Does your
      Health Insurance Plan know more than your Doctor?

PMID- 28496626
TI  - Atrial Fibrillation Complicating Congestive Heart Failure: Electrophysiological
      Aspects And Its Deleterious Effect On Cardiac Resynchronization Therapy.
AB  - More successful recognition and treatment of cardiovascular risk factors and
      diseases continues to decrease mortality and increase the proportion of elderly
      population. Therefore, there are more people with increased risk of developing
      heart failure and atrial fibrillation in the course of their lives. Atrial
      fibrillation (AF) can complicate the course of congestive heart failure (HF)
      leading to acute pulmonary edema. The prevalence of AF, in patients with heart
      failure, increases with the severity of the disease, reaching up to 40% in
      advanced cases. In these HF patients, AF is an independent predictor of morbidity
      and mortality increasing the risk of death and hospitalization. Despite the
      excellent results obtained with different drugs, the optimal medical treatment
      can fail in the intention to improve symptoms and quality of life of patients
      with severe HF. Thus, the necessity to use cardiac devices emerges facing the
      failure of optimal medical treatment in order to achieve hemodynamic improvement
      and correction of the physiopathological alterations. Cardiac resynchronization
      therapy (CRT) can reduce the interventricular and intraventricular mechanical
      dissynchrony in HF patients. It has been shown that CRT increases the left
      ventricular filling time, decreases septal dissynchrony, mitral regurgitation,
      and left ventricular volumes allowing a hemodynamic improvement. However, the
      development of AF in this setting can avoid the beneficial effects of CRT.
      Therefore, this manuscript will review the available data on this topic, the
      electrophysiological aspects of AF, to determine what can be done in the event of
      an AF complicating congestive HF in CRT patients.

PMID- 28496627
TI  - The Phrenic Nerve And Atrial Fibrillation Ablation Procedures.
AB  - Radiofrequency ablation is increasingly used as an option to optimally manage
      patients with symptomatic atrial fibrillation. Presently, ablationists strive to
      improve success rates, particularly with persistent atrial fibrillation, while
      simultaneously attempting to reduce complications. A well-recognized complication
      with atrial fibrillation ablation is injury to the phrenic nerve giving rise to
      diaphragmatic paresis and patient discomfort.Phrenic nerve damage may occur when
      performing common components of atrial fibrillation ablation including pulmonary
      and superior vena caval isolation. The challenge for ablationists is to
      successfully target the arrhythmogenic substrate while avoiding this
      complication. In order to do this, a thorough knowledge of phrenic nerve anatomy,
      points in the ablation procedure where nerve damage is more likely, and an
      understanding of the presently utilized techniques to avoid this complication is
      required. In addition, when this complication does arise, prompt recognition of
      its occurrence, knowledge of the natural history, and available methods for
      management are needed.In this review, we discuss the underlying anatomic
      principles, techniques of avoiding phrenic nerve damage, and presently available
      methods of diagnosing and managing this complication.

PMID- 28496628
TI  - Esophageal Dilatation Post - Gastric Banding And Catheter Ablation For Atrial
      Fibrillation: A Case Report.
AB  - Esophageal injury is a potential serious complication of catheter ablation for
      atrial fibrillation. We report a case of significant esophageal dilatation
      following previous laparascopic gastric banding in a patient with permanent
      atrial fibrillation undergoing a pulmonary vein isolation procedure.

PMID- 28496625
TI  - Atrial Remodeling And Atrial Fibrillation: Mechanistic Interactions And Clinical
      Implications.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. The
      prevalence of AF increases dramatically with age and is seen in as high as 9% of
      individuals by the age of 80 years. In high-risk patients, the thromboembolic
      stroke risk can be as high as 9% per year and is associated with a 2-fold
      increase in mortality. Although the pathophysiological mechanism underlying the
      genesis of AF has been the focus of many studies, it remains only partially
      understood. Conventional theories focused on the presence of multiple re-entrant
      circuits originating in the atria that are asynchronous and conducted at various
      velocities through tissues with various refractory periods. Recently, rapidly
      firing atrial activity in the muscular sleeves at the pulmonary veins ostia or
      inside the pulmonary veins have been described as potential mechanism,. AF
      results from a complex interaction between various initiating triggers and
      development of abnormal atrial tissue substrate. The development of AF leads to
      structural and electrical changes in the atria, a process known as remodeling. To
      have effective surgical or catheter ablation of AF good understanding of the
      possible mechanism(s) is crucial.Once initiated, AF alters atrial electrical and
      structural properties that promote its maintenance and recurrence. The role of
      atrial remodeling (AR) in the development and maintenance of AF has been the
      subject of many animal and human studies over the past 10-15 years. This review
      will discuss the mechanisms of AR, the structural, electrophysiologic, and
      neurohormonal changes associated with AR and it is role in initiating and
      maintaining AF. We will also discuss briefly the role of inflammation in AR and
      AF initiation and maintenance, as well as, the possible therapeutic interventions
      to prevent AR, and hence AF, based on the current understanding of the
      interaction between AF and AR.

PMID- 28496629
TI  - Masquerading Tachycardi.

PMID- 28496630
TI  - Evolution of Paroxysmal Atrial Fibrillation to Persistent or Permanent Atrial
      Fibrillation: Predictors of Progression.
AB  - Introduction: Paroxysmal atrial fibrillation (PAF) eventually progresses to
      persistent and permanent AF. The predictors of progression from PAF to persistent
      and permanent AF are poorly understood. Methods: Electronic medical records of
      437 patients with PAF were reviewed in a retrospective cohort study. Patients
      were followed in time and progression to persistent/permanent AF was recorded.
      Demographic, clinical and echocardiographic information was collected. A logistic
      regression analysis was performed to identify predictors of progression to
      persistent/permanent AF. Results: Over a mean duration of 57.3+/-55.9 months,
      32.4% of patients progressed to persistent/permanent AF. Mean age of the
      population was 67.9+/-13.4 years with 57% males and 92% Caucasian. Univariate
      analysis identified higher body higher mass index (BMI), cardiomyopathy,
      diabetes, valvular heart disease (VHD), larger left atrial size (LA) and higher
      pulmonary artery pressure as predictors of progression. Multivariate logistic
      regression analysis larger left atrial size (OR 1.46, CI 1.05-2.04, P 0.002),
      cardiomyopathy (OR 2, CI 1.1- 3.3, P 0.003), and moderate to severe valvular
      heart disease (OR 3.3, CI 1.4-5, P 0.008) as significant predictors of
      progression to persistent/permanent AF. Conclusions: Our study shows that PAF
      patients with larger LA, valvular heart disease and cardiomyopathy predict
      progression of PAF to persistent/permanent AF. Higher BMI and cardiomyopathy
      predicted progression to persistent AF while larger LA size and VHD predicted
      progression to permanent AF.

PMID- 28496631
TI  - Atrial Fibrillation Ablation: First-Line Therapy?
AB  - Background: Ablation for atrial fibrillation (AF) is a widely-accepted treatment
      for this arrhythmia. Ablation is traditionally reserved for second-line therapy
      in patients who have failed drug therapy, but it may be ready for first-line
      treatment. Objective: This article outlines the rationale for using ablation as
      first-line therapy for AF. Findings: AF increases both morbidity and mortality.
      Unfortunately, drug-based therapy for AF is very ineffective and may contribute
      adversely to both patient morbidity and mortality. Ablation addresses the root
      causes of AF and thus may be curative. The technique for ablation has become
      quite consistent and the outcomes better than those with drug therapy. The
      complication risk is also acceptably low. There is even preliminary evidence to
      suggest that AF ablation is superior as first-line treatment compared to drugs.
      Conclusion: AF ablation is rapidly evolving towards becoming first-line therapy
      for some patients with this debilitating arrhythmia.

PMID- 28496632
TI  - The Autonomic Nervous System and Atrial Fibrillation:The Roles of Pulmonary Vein
      Isolation and Ganglionated Plexi Ablation.
AB  - After the sequential successes of catheter ablation for the treatment of pre
      excitation syndromes (WPW), junctional reentry (AVNRT) atrial flutter (AFL) and
      ventricular arrhythmias, clinical electrophysiologists have focused on the
      myocardial basis of atrial fibrillation (AF). Thus, the strategy for ablation of
      drug and cardioversion refractory AF was to isolate the myocardial connections
      from the focal firing pulmonary veins (PVs) in addition to altering the atrial
      substrate maintaining AF. However, the overall success rates have not achieved
      those of the other types of ablation procedures. In this review we have
      summarized the favorable aspects and drawbacks of pulmonary vein isolation (PVI).
      As for the role of the Intrinsic Cardiac Autonomic Nervous System (ICANS), both
      basic and clinical evidence has shown that ganglionated plexi (GP) stimulation
      promotes initiation and maintenance of AF, and that GP ablation reduces
      recurrence of AF following catheter or surgical ablation of these structures.
      Based on these findings, the GP Hyperactivity Hypothesis has been proposed to
      explain, at least in part, the mechanistic basis for the focal form of AF. For
      example, PV isolation may not always be necessary for elimination of AF, as in
      the early stages of paroxysmal AF. GP ablation alone, in these cases, may suffice
      for focal AF termination. In the persistent and long standing persistent forms
      the substrate for AF may be more extensive and therefore require GP ablation plus
      PV isolation and/or CFAE ablations. Clinical reports, both catheter based as well
      as minimally invasive surgical procedures, which include PVI plus GP ablation
      have shown relatively long-term success rates much closer to or equal to those
      achieved by myocardial ablation procedures in patients with WPW, AVNRT and AFL.

PMID- 28496634
TI  - Laser Ablation Of Atrial Fibrillation: Mid-term Clinical Experience.
AB  - Background: Atrial Fibrillation is known to account for one third of all the
      strokes caused in the US in the population above the age of 70. Patients treated
      with the surgical Cox MAZE operation have been shown to have a 150 fold decrease
      in the incidence of stroke over an 18 year period. However, the original Cox MAZE
      although extremely successful in treating atrial fibrillation and decreasing the
      incidence of strokes was not performed widely because of complexity and
      invasiveness of the procedure. A variety of alternative energy based curative
      ablation strategies are now available for more minimally invasive therapeutic
      management of atrial fibrillation (AF). In this communication, we report our
      clinical experience in AF therapy utilizing laser energy ablation technology.
      Methods: Fifty two consecutive AF patients underwent concomitant or isolated
      ablation prior to any coexisting cardiac procedures that included CABG (coronary
      artery bypass surgery, MV (mitral valve) or AV (aortic valve) repairs. All
      patients had an epicardially based ablation pattern with basic lesions being en
      bloc box type pulmonary vein isolation which included the antral surface of the
      left atrium, directed ganglionectomies of the the right anterior and inferior
      ganglions, posteriomedial ablation of the IVC ( inferior vena cava), and a right
      isthmus ablation. Twenty seven patients had ligation of their left atrial
      appendage, 14 patients had resection of the ligament of Marshall, and three
      patients had endocardial placed lesions of a mitral annular connecting type
      lesion. In order to maintain the patients in normal sinus rhythm (NSR),
      electrical cardioversion and anti-arrhythmic drugs were employed as required.
      Results: At a median follow-up of 250 days, 44 of the total 52 patients (84.6%)
      exhibited NSR.. No complications or mortality were reported due to the laser
      procedure. Conclusion: Laser ablation was successfully and safely used for
      endocardial and epicardial AF ablation concomitant to other cardiovascular
      procedures and in the lone atrial fibrillation treatment utilizing a two port
      thoracoscopic approach.

PMID- 28496633
TI  - Cost-Effectiveness Of Catheter Ablation Treatment For Patients With Symptomatic
      Atrial Fibrillation.
AB  - Background: Atrial Fibrillation is the most common cardiac arrhythmia. It
      increases the risk of thromboembolic events and many atrial fibrillation patients
      suffer quality of life impairment due to disturbed heart rhythm. Pulmonary vein
      isolation using radiofrequency catheter ablation treatment is aimed at
      maintaining sinus rhythm ultimately improving quality of life. Randomized
      clinical trial have shown that catheter ablation is more effective than
      antiarrhythmic drugs for the treatment of atrial fibrillation, but its impact on
      quality of life and cost-effectiveness has not been widely studied. Aims: To
      assess the cost-effectiveness of radiofrequency ablation (RFA) vs. antiarrhythmic
      drug (AAD) treatment, among symptomatic atrial fibrillation patients not
      previously responding to AAD. Methods: A decision-analytic Markov model was
      developed to assess costs and health outcomes in terms of quality adjusted life
      years (QALYs) of RFA and AAD over a lifetime time horizon. We conducted a
      literature search and used data from several sources as input variables of the
      model. One-year rates of atrial fibrillation with RFA and AAD, respe tively, were
      available from published randomized clinical trials. Other data sources were
      published papers and register data. Results: The RFA treatment strategy was
      associated with reduced costs and an incremental gain in QALYs compared to the
      AAD treatment strategy. The results were sensitive to whether long-term quality
      of life improvement is maintained for the RFA treatment strategy and the risk of
      stroke in the different atrial fibrillation health states. Conclusion: This study
      shows that the short-term improvement in atrial fibrillation associated with RFA
      is likely to lead to long-term quality of life improvement and lower costs
      indicating that RFA is cost-effective compared to AAD.

PMID- 28496635
TI  - Epicardially Based Pulmonary Vein Isolation for the Treatment of Atrial
      Fibrillation Utilizing Laser Energy in the Pig Model.
AB  - Purpose: Atrial fibrillation is a common disease that increases the incidence of
      cerebrovascular embolic events and cardiac dysfunction. Foci for atrial
      fibrillation have been mapped and found to be for the most part located within
      the ostia of the pulmonary veins. Since 2002 microwave and radiofrequency energy
      sources have been used to create pulmonary vein isolation lesions. This abstract
      summarizes the safety and efficacy of performing vein isolation lesions with
      laser as the energy source. Description: The large pig model was utilized for
      creation of isolation lesions around the pulmonary veins. The Optimaze E360
      Surgical Ablation Handpiece from Edwards Lifesciences was utilized, it contains a
      4 centimeter diffusing diode laser (980nm). All six of the pig models tolerated
      the procedure with a 40-day normal post procedure growth pattern. Evaluation:
      Upon reoperation one pig developed ventricular fibrillation with resection of
      adhesions. All five remaining pigs were fully tested and demonstrated complete
      electrical isolation. Gross pathology revealed intact well defined ablation
      lesions with an otherwise completely normal cardiac structure. All lesions were
      fully transmural at each histological sectioned point. Conclusions: Laser
      technology in the form of the Optimaze E360 Surgical Ablation Handpiece from
      Edwards Lifesciences, is able to reliably and consistently produce well defined
      electrical isolation scars around the pulmonary veins. This device is also
      amenable to performing the isolation procedure using a minimally invasive
      approach.

PMID- 28496636
TI  - Paroxysmal Lone Atrial Fibrillation Is Associated With An Abnormal Atrial
      Substrate: Characterizing The "Second Factor".

PMID- 28496637
TI  - Dronedarone For Atrial Fibrillation: Unbridled Enthusiasm Or Just Another Small
      Step Forward?

PMID- 28496638
TI  - Percutaneous Left Atrial Appendage Exclusion Therapy: Who, Why and How?
AB  - Purpose: Patients with atrial fibrillation are at an increased risk of having a
      cardio embolic stroke. Stroke is a leading cause of death and disability
      worldwide. Current guidelines recommend an antithrombotic regimen to prevent
      thromboembolism in medium and high risk patients with AF. However, a substantial
      number of patients are not eligible for this therapy. The exclusion of the left
      atrial appendage (LAA) from circulation seems to be an alternative strategy for
      stroke prevention in AF. This review focuses on the different strategies for LAA
      exclusion with special focus on the WATCHMAN Device. Two devices are currently in
      use for percutaneous transcatheter occlusion of the LAA: the WATCHMAN(r) - device
      and the AMPLATZER(r) -septal occluder. For both devices safety and feasibility
      data are available. Additionally about 200 patients received a PLAATO(r) -device-
      which is currently no more available due to economic reasons. Patients treated
      with the PLAATO device were at high risk for thromboembolic stroke and had
      contraindications for oral anticoagulation therapy. The Watchman(r) -device was
      implanted in 800 patients that were eligible for long-term anticoagulation
      therapy with a moderate risk for thromboembolic stroke due to non-valvular AF.
      Summary: For both devices, a reduction in the risk of stroke was documented and
      device implantation was shown to be safe and feasible. Provided the ongoing
      trials show noninferiority to oral anticoagulation, another therapeutic option
      will become available to prevent ischemic strokes.

PMID- 28496639
TI  - Pulmonary Vein Isolation using a High Density Mesh Ablator Catheter:
      Incorporation of three-Dimensional Navigation and Mappin.
AB  - Background: We evaluated the use of a novel High Density Mesh Ablator (HDMA)
      catheter in combination with three-dimensional navigation for the treatment of
      paroxysmal atrial fibrillation. Methods: The HDMA catheter was used to carry out
      pulmonary vein isolation in a consecutive series of patients. Three-dimensional
      geometry of the left atrial-pulmonary vein (LA-PV) junctions were first created
      with the HDMA catheter. Ostial, proximal and distal sites within the pulmonary
      veins were tagged with catheter shadows on the created geometry to allow for re
      interrogation of these exact sites after ablation. Results: The HDMA catheter was
      successfully used to create three dimensional geometry of the LA-PV junction in a
      total of 20 pulmonary veins which involved 5 patients. In all cases, ostial
      ablation alone was sufficient to achieve electrical isolation. No significant
      pulmonary vein stenosis was seen acutely after ablation. Conclusion: We describe
      the successful use of the novel HDMA catheter to create three-dimensional
      geometry of the LA-PV junction to assist with pulmonary vein isolation.

PMID- 28496640
TI  - Review of Dominant Frequency Analysis in Atrial Fibrillation.
AB  - Significant advancements have been made in the technology and approach to
      catheter ablation of atrial fibrillation (AF). Pulmonary vein isolation has
      emerged as the dominant strategy in this procedure and has fueled innovations in
      catheter design as well as various mapping and navigation systems. Mapping and
      targeting of complex fractionated atrial electrograms has also emerged as an
      additional or alternate strategy employed by some ablationists. Recently,
      attention is being drawn to a new approach targeting atrial sites with high
      dominant frequencies (DF) derived from their electrograms. This article is a
      review of the basic concepts of DF, the relevant literature behind DF analysis in
      AF, and the potential clinical applicability of DF analysis for catheter
      ablation.

PMID- 28496641
TI  - Atrial Fibrillation in Hypertrophic Obstructive Cardiomyopathy - Antiarrhythmics,
      Ablation and More!
AB  - Hypertrophic cardiomyopathy (HCM) is a genetic disease of the cardiac sarcomere
      with an autosomal dominant pattern of inheritance. Patients with HCM are at high
      risk of developing atrial fibrillation (AF) particularly in the setting of
      advanced diastolic dysfunction and left atrial enlargement. AF is a marker of
      increased mortality and morbidity and results in a significant reduction in
      quality of life. Antiarrhythmic medications improve symptoms and reduce AF
      recurrence, but few are safe and there exists little data to guide their long
      term use in HCM. Non-pharmacologic approaches have emerged and have equal or
      greater efficacy than pharmacologic approaches. Although these approaches are
      promising, the long-term impact on atrial function needs to be carefully studied
      as it may impact quality of life in patients that age in the setting of a
      progressive diastolic disease disorder. Nonetheless, with the significant impact
      of AF in HCM, rhythm control strategies are often required. The understanding of
      rhythm control strategies in HCM, an often rapidly progressive diastolic
      dysfunction disorder, may provide insight in how to treat the much more prevalent
      AF patient with hypertensive cardiomyopathy. Regardless of treatment strategy
      (rhythm or rate control) patients are a moderate to high risk of thromboembolism
      and until data are available to suggest otherwise require long-term warfarin
      anticoagulation.

PMID- 28496642
TI  - Role of Inflammation in Early AF Recurrence After PV Isolation.

PMID- 28496643
TI  - The Role of Intracardiac Echocardiography in Atrial Fibrillation Ablation.
AB  - Radiofrequency catheter ablation of pulmonary veins has emerged as an effective
      therapy for patients with symptomatic atrial fibrillation. Advances in real-time
      intracardiac echocardiography with 2D and Doppler color flow imaging have led to
      it integration in atrial fibrillation ablation procedures. It allows imaging of
      the left atrium and pulmonary veins, including identification of anatomic
      variations. It has an important role in guiding transseptal catheterization,
      imaging the pulmonary vein ostia, assisting in accurate placement of mapping and
      ablation catheters, monitoring lesion morphology and flow changes in the ablated
      pulmonary veins, hence allowing titration of energy delivery. Importantly, it
      allows instant detection of procedural complications.

PMID- 28496644
TI  - Management of the Asymptomatic Patient After Catheter Ablation of Atrial
      Fibrillation.
AB  - Ablative therapy for atrial fibrillation is becoming more commonplace, and some
      minimally symptomatic or asymptomatic patients will be referred for ablative
      therapy. Reasons to ablate asymptomatic patients include young age and/or the
      presence of a tachycardia induced cardiomyopathy; in addition, some symptomatic
      patients may become asymptomatic after ablation. Managing these patients can be
      challenging. In this review, we will discuss the use of telemetric monitoring,
      antiarrhythmic drugs and anticoagulation after ablation in asymptomatic patients
      with atrial fibrillation.

PMID- 28496645
TI  - C-Reactive Protein and The Risk of Atrial Fibrillation: A Systematic Review and
      Meta-Analysis.
AB  - There is increasing evidence linking C-reactive protein (CRP) and atrial
      fibrillation (AF). Despite the abundance of literature, confusion exists
      regarding this association because of inconsistent results. MEDLINE and Cochrane
      Controlled Trials Register databases were carefully searched through July, 2009
      combining the following terms "C-reactive protein" and "atrial fibrillation".
      Reference lists of selected articles and reviews were also screened to identify
      additional relevant studies. Of the 129 studies initially identified, 8 studies
      with 7507 subjects (719 with AF) were included in the meta-analysis. Analysis
      yielded a relative risk of 1.63 (1.43, 1.86) for occurrence of AF when CRP level
      was above a cut off of 3-3.5 mg/l. When 3 studies with data on a higher cut off
      of 4.5-5.0 mg/l were analyzed separately, the relative risk was 4.03 (3.1, 5.25).
      Our study suggests that elevated CRP is associated with increased risk for AF.
      The risk appears incremental with higher CRP levels conferring proportionately
      increased risk. There is an urgent need for further large scale, well designed
      prospective studies to assess the relationship between CRP and AF.

PMID- 28496646
TI  - Level Of Natriuretic Peptide Determines Outcome In Atrial Fibrillation.
AB  - : Background: Natriuretic peptide (NP) is high in atrial fibrillation (AF) and
      may decrease after cardioversion to sinus rhythm and the levels of atrial NP
      (ANP) and brain NP (BNP) in different types of AF and whether ANP and BNP have
      predictive values for relapsed AF have not been determined. Purpose: We aimed to
      examine the levels of ANP and BNP in AF to determine their roles in different
      types of AF, including a predictive value in relapsed AF. Methods and Results:
      ANP and BNP were measured in 100 consecutive patients with AF and without heart
      dysfunction at baseline and in 20 controls. All patients had higher levels than
      controls (p<0.01). After cardioversion treatment with antiarrhythmic therapy, 40
      patients failed to cardioversion successfully and still showed AF, whereas 60
      patients were successful. ANP and BNP levels decreased significantly after
      cardioversion (163.55+/-54.27pg/ml vs. 200.20+/-55.63 pg/ml; 124.15+/-43.00 pg/ml
      vs. 161.99+/-48.04 pg/ml, for ANP and BNP respectively, both p<0.0001). 18 of the
      60 successfully cardioverted patients had AF recurred within 24 hours, who were
      then excluded from 500-day follow-up and the remaining 42 patients were enrolled.
      During 500-day follow-up period, AF relapsed in 16 patients. Comparing with the
      42 patients, the 16 patients showed higher concentrations of ANP (187.72+/-32.79
      pg/ml vs. 138.42+/-30.65 pg/ml, p<0.0001). Besides, both ANP and BNP were
      significantly higher in the relapsed patients than those remained SR during
      follow-up (153.38+/-29.61pg/ml vs. 129.21+/-27.98pg/ml for ANP, p=0.01 and
      147.41+/-25.95pg/ml vs. 121.87+/-20.53pg/ml for BNP, p=0.001). The area under the
      receiver-operating characteristic curve was 0.799 for BNP and 0.706 for ANP in
      predicting a relapse of AF. Using the BNP optimized cut-off level of 138 pg/ml,
      relapsed AF can be predicted with relatively acceptable accuracy. CONCLUSIONS:
      ANP and BNP decrease significantly after cardioversion in patients with AF, and
      both can be useful predictors of relapsed AF.

PMID- 28496647
TI  - Monomorphic Outflow Tract Ventricular Tachycardia: Unique Presenting
      Manifestation of Gitelman's Syndrome.

PMID- 28496648
TI  - Dabigatran, A Direct Thrombin Inhibitor, In Atrial Fibrillation: Is It Already
      Time For A Change In Oral Anticoagulation Therapy?

PMID- 28496649
TI  - Effect of Statins in Preventing Postoperative Atrial Fibrillation Following
      Cardiac Surgery.
AB  - Background: Postoperative occurrence of AF has been associated with less
      favorable outcomes in patients undergoing cardiac surgery and may result in
      increased postoperative morbidity and mortality. Objectives: A focused clinical
      question was designed and a Meta-analysis of published studies was performed to
      identify the effect of preoperative use of statins on the occurrence of AF after
      cardiac surgery. Methods: Using the Medline database, the Cochrane clinical
      trials database and online clinical trial databases, we reviewed all RCTs and
      observational studies examining the effect of statins on AF occurrence following
      cardiac surgery. We searched for literature published before April 2009 and
      earlier. Results: This analysis identified 6 studies (observational studies)
      which examined the effect of preoperative use of statins on AF occurrence
      following cardiac surgery, involving 10165 patients. Contradictory to most of
      previous studies, the overall outcomes suggested that the statins group did not
      have a significant decrease in AF occurrence following cardiac surgery comparing
      to control group (P = 0.19). Conclusions: The preoperative medication of statins
      showed no significant decrease in AF occurrence following cardiac surgery in this
      Meta-analysis result. More prospective studies and researches are needed to
      explore and demonstrate the accurate mechanism and effect of statins on
      postoperative AF.

PMID- 28496650
TI  - Current Perspectives: Rheumatic Atrial Fibrillation.

PMID- 28496651
TI  - Atrial Fibrillation in Athletes - The Story Behind The Running Hearts.

PMID- 28496653
TI  - Determining Esophageal Anatomy With A New Electroanatomical Mapping System.

PMID- 28496652
TI  - An Update on the Energy Sources and Catheter Technology for the Ablation of
      Atrial Fibrillation.
AB  - The ablation of atrial fibrillation (AF) is an area of intense research in
      cardiac electrophysiology. In this review, we discuss the development of catheter
      based interventions for AF ablation. We outline the pathophysiologic and anatomic
      bases for ablative lesion sets and the evolution of various catheter designs for
      the delivery of radiofrequency (RF), cryothermal, and other ablative energy
      sources. The strengths and weaknesses of various specialized RF catheters and
      alternative energy systems are delineated, with respect to efficacy and patient
      safety.

PMID- 28496654
TI  - The Utility of Ambulatory Electrocardiographic Monitoring for Detecting Silent
      Arrhythmias and Clarifying Symptom Mechanism in an Urban Elderly Population with
      Heart Failure and Hypertension: Clinical Implications.
AB  - Background: Atrial and ventriclar tachyarrhythmias, as well as bradyarrhythmias,
      in the elderly with heart failure (HF) and/or hypertension (HTN) have been well
      documented. However, the frequency of these arrhythmias, whether silent or
      symptomatic, and their association with subsequent cardiac events has not been
      well defi ned in patients 65 years or older with HF and other cardiovascular risk
      factors. Objective: To assess the value of 2 weeks of remote, transtelephonic
      cardiac monitoring for detecting arrhythmias in an elderly, urban population
      living with HF. Methods: Fi" y-four patients with a history of systolic HF and/or
      HTN were consented and enrolled. All wore an auto triggered cardiac loop monitor
      for 2 weeks that captures EKG data and both silent and symptomatic arrhythmias
      were recorded. Results: Mean age was 73 +/- 6 years with 59% of subjects were
      females, 74% Hispanic, 22% black, and 4% white/other. All patients had HF and 94%
      had HTN. From the cardiac monitoring, 72% demonstrated ectopic atrial and
      ventricular activity, and 1 paroxysmal episode of atrial fi brillation was
      documented. In addition, 3 subjects had signifi cant non-sustained ventricular
      tachycardia, and 4 individuals had severe bradycardia recorded on cardiac
      monitoring. These 7 individuals underwent placement of an implantable
      cardioverter defi brillator (ICD) or pacemaker based on the documented
      arrhythmias which may have otherwise gone undetected. Conclusions: A substantial
      proportion of patients exhibited cardiac arrhythmias. Future morbidity was
      prevented because of the detection of arrhythmias on monitoring that led to
      specifi c therapies such as pacemaker or ICD implantation which otherwise may not
      have been implemented.

PMID- 28496655
TI  - Electrophysiological Changes of the Atrium in Patients with Lone Paroxysmal
      Atrial Fibrillation.
AB  - Introduction: Paroxysmal atrial fibrillation (PAF) is a common arrhythmia, and it
      is associated with various cardiac conditions. On the other hand, lone PAF has no
      identifiable underlying cause, and can occur any time for no apparent reason. The
      underlying causes may modify the electrophysiological properties of the atrium in
      different ways and extent. However this setting may be different in patients with
      lone PAF. We sought to investigate the atrial electrophysiological properties in
      lone PAF. Material and Methods: This study included 62 control subjects (Control
      group) and 58 patients with lone PAF (LAF group). The following atrial
      vulnerability parameters induced by programmed atrial stimulation were assessed
      and quantitatively measured: 1) the atrial effective refractory period (ERP), 2)
      the atrial conduction delay (CD) zone, and 3) the maximum CD. Results: The mean
      atrial ERP of the Control group was 215+/-29 ms, and that of LAF group was 208+/
      28 ms, p<0.05. The mean atrial CD zone of the LAF group was (50+/-28 ms)
      significantly greater than that of controls (34+/-22 ms) (p<0.01). The mean
      maximum CD of the LAF group (62+/-29 ms) was also significantly greater than that
      of controls (43+/-20 ms) (p<0.01). Conclusions : There is a greater conduction
      delay of the atrium and shorter refractoriness in patients with lone PAF.
      Patients without underlying causes for the development of PAF exhibit
      abnormalities in the electrophysiological properties of the atrium.

PMID- 28496657
TI  - Is Isolation of Arrhythmogenic Pulmonary Veins Sufficient for the Long-term
      Efficacy of Atrial Fibrillation Ablation?

PMID- 28496656
TI  - Lone AF - Etiologic Factors and Genetic Insights into Pathophysiolgy.
AB  - Ever since atrial fibrillation (AF) was first recognized in young people (so
      called "lone" AF) over 4 decades ago, there has been increasing focus on
      determining the underlying pathophysiology of the condition. Although lone AF is
      presumed to be a highly heterogeneous disease, recent studies have identified
      novel risk factors such as inflammation, oxidative stress, endurance sports and
      genetics, for the arrhythmia. This monograph aims to highlight some of the recent
      advances in our understanding of the molecular pathophysiology of lone AF
      especially insight provided by contemporary genetic studies. These insights may
      provide novel therapeutic targets for treatment of this challenging arrhythmia in
      young patients.

PMID- 28496658
TI  - AF Termination: the Holy Grail of Persistent AF Ablation?

PMID- 28496659
TI  - Atrial Fibrillation Susceptibility Alleles on Chromosome 4q25 Modulate Response
      to Catheter Ablation.

PMID- 28496661
TI  - Use of Ivabradine in Postural Orthostatic Tachycardia Syndrome.
AB  - Postural orthostatic tachycardia syndrome (POTS) is characterized by
      inappropriate increase in heart rate on assuming upright position from a supine
      position without a necessary drop in blood pressure. Etiology of this condition
      is complex and multifactorial. Autonomic dysfunction,[1] hypovolemia,[2] hyper
      responsiveness of beta adrenergic receptors[3] with associated elevations of
      plasma norepinephrine levels have been implicated as underlying pathophysiologic
      mechanisms. Beta blockers have previously been used to treat this condition.
      Ivabradine which selectively inhibits If ion current in the sino atrial node, has
      been reported to be useful in patients with POTS.[4,5] We present one further
      such case of POTS successfully treated by Ivabradine.

PMID- 28496660
TI  - Electrophysiological Changes of the Atrium in Patients with Lone Paroxysmal
      Atrial Fibrillation.
AB  - BACKGROUND: The "Pill-in-Pocket" (PIP) is an approach to atrial fibrillation (AF)
      where oral anti-arrhythmics at 75% to 100% of the normal daily dose, given as a
      single dose, is used to convert recent-onset AF. Pro-arrhythmic risk has limited
      this approach to patients without structural heart disease (SHD). Ranolazine is
      an anti-anginal agent, which inhibits the abnormal late Na+ channel current
      resulting in decreased Na+/Ca++ overload. This inhibits after-depolarizations and
      reduces pulmonary vein firing, which have been implicated in the initiation and
      propagation of AF. Ranolazine increases atrial refractoriness and has no known
      pro-arrhythmic affects. Ranolazine is routinely given to patients with SHD. The
      ability of Ranolazine to terminate AF in man has not been described but if useful
      could be a safer PIP agent with application in the presence or absence of SHD. We
      describe our experience using oral Ranolazine to convert new or recurrent AF.
      METHOD: 2000 mg of ranolazine was administered to 35 patients with new (16
      patients) or recurrent (19 patients) AF of at least 3 but not greater than 48
      hours duration. Clinical features, echocardiographic data, and SHD were noted.
      Success was defined as restoring sinus rhythm within 6 hours of Ranolazine.
      RESULTS: All but 4 patients had some form of SHD. Twenty-five patients were in
      the hospital, 5 were in the office, and 5 were at home at the time Ranolazine was
      administered. Twenty-five of 35 patients converted to sinus rhythm. No pro
      arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived
      intolerance were noted. The 71% conversion rate was comparable to other reported
      PIP protocols and much higher than reported placebo conversion rates.
      CONCLUSIONS: High dose oral Ranolazine shows utility as a possible safe agent to
      convert new or recurrent AF. Larger placebo-controlled studies would appear to be
      warranted.

PMID- 28496662
TI  - Invasive Management of Atrial Fibrillation and the Elderly.

PMID- 28496663
TI  - Is AF Ablation Cost Effective?
AB  - The use of catheter ablation to treat AF is increasing rapidly, but there is
      presently an incomplete understanding of its cost-effectiveness. AF ablation
      procedures involve significant up-front expenditures, but multiple randomized
      trials have demonstrated that ablation is more effective than antiarrhythmic
      drugs at maintaining sinus rhythm in a second-line and possibly first-line rhythm
      control setting. Although truly long-term data are limited, ablation, as compared
      with antiarrrhythmic drugs, also appears associated with improved symptoms and
      quality of life and a reduction in downstream hospitalization and other health
      care resource utilization. Several groups have developed cost effectiveness
      models comparing AF ablation primarily to antiarrhythmic drugs and the model
      results suggest that ablation likely falls within the range generally accepted as
      cost-effective in developed nations. This paper will review available information
      on the cost-effectiveness of catheter ablation for the treatment of atrial
      fibrillation, and discuss continued areas of uncertainty where further research
      is required.

PMID- 28496664
TI  - Ranolazine for Atrial Fibrillation: Too Good to be True?

PMID- 28496665
TI  - Commentary on : New-Onset Atrial Fibrillation Predicts Long-Term Mortality After
      Coronary Artery Bypass Graft by El-chami et.al.

PMID- 28496666
TI  - Supraventricular Ectopic Activity: When Excessive it is not all Benign!

PMID- 28496667
TI  - Stroke Prevention in Atrial Fibrillation.
AB  - Non-valvular atrial fibrillation is a common and from a neurological perspective
      the most significant cardiac arrhythmia with a growing world-wide incidence. It
      also carries a significant associated morbidity and mortality, with cardioembolic
      strokes arguably being the most disabling sequelae. This brief review will
      highlight the important studies and the latest treatment modalities available for
      stroke prevention in patients with non-valvular atrial fibrillation.

PMID- 28496668
TI  - Endurance Sport Practice and Atrial Fibrillation.

PMID- 28496669
TI  - Effect of High-dose Telmisartan on the Prevention of Recurrent Atrial
      Fibrillation in Hypertensive Patients.
AB  - Background: Telmisartan has been shown to exert an equivalent action as ramipril
      on the prevention of cardiovascular events, but the dose-dependent actions of
      telmisartan on the prevention of events remain unknown. Objective: We
      investigated the dose-dependent effects of telmisartan on the prevention of AF in
      patients associated with risk factors. Methods: One hundred hypertensive patients
      were randomized to take 40 mg (low-dose group: n=57) or 80 mg (high-dose group:
      n=43) of telmisartan for 24 months. The primary endpoints were defined as a new
      development and/or recurrence of atrial fibrillation (AF). Results: The mean
      values of the blood pressure in both groups decreased significantly and to
      similar degrees after 24 months, in the low-dose (p < 0.01) and high-dose (p <
      0.01) groups. At the end of the follow-up, the incidence of AF was lower in the
      high-dose group than in the low-dose group (p < 0.05). Moreover, the proportion
      of AF recurrences in the patients with a past history of paroxysmal AF was lower
      in the high-dose group than in the low-dose group (p < 0.05). Further, using a
      logistic regression model, there were no risk factors associated with the
      incidence of AF. Conclusion: The results indicated that telmisartan in low doses
      was as effective in controlling the blood pressure as in high doses, but high
      doses of telmisartan had beneficial effects on preventing the recurrence of AF in
      hypertensive patients.

PMID- 28496670
TI  - Atrial Tachycardias Occurring After Atrial Fibrillation Ablation: Strategies for
      Mapping and Ablation.
AB  - The occurrence of left atrial tachycardias (AT) after catheter ablation for
      atrial fibrillation (AF) is common, especially after more extensive ablation of
      persistent AF. These AT are invariably symptomatic and often do not respond to
      medical therapy. The initial strategy involves ventricular rate control,
      cardioversion, and observation as some tachycardias may resolve with time. For
      persistent ATs, effective management frequently requires catheter intervention.
      Careful characterization of the tachycardia mechanism is essential in designing
      an effective ablation strategy that would also avoid further creation of pro
      arrhythmic substrate. With this review, we summarize the incidence, mechanism,
      diagnosis and treatment of ATs occurring after AF ablation.

PMID- 28496672
TI  - The Power of One: a Highly Detailed, Log-Based, Case Example that Clearly
      Demonstrates the Effective Use of Ranolazine for the Control of Progressive
      Atrial Fibrillationn.

PMID- 28496671
TI  - Management of Atrial Fibrillation in Pregnancy.
AB  - Pregnancy is accompanied by a variety of cardiovascular changes in normal women;
      all of these changes are thought to promote arrhythmogenesis. Atrial fibrillation
      is unusual during pregnancy and it can represent a benign, self-limited lone
      atrial fibrillation or can be hemodynamically significant in parturient with or
      without structural heart disease. Management of atrial fibrillation should be the
      same as in non-pregnant women, but requires faster intervention, even in patients
      with a normal heart function, and cautious use of medication to avoid harm to the
      fetus. We might remember that synchronized electrical cardioversion has been
      performed safely during all stages of pregnancy.

PMID- 28496673
TI  - Angiotensin Receptor Blockers for the Prevention of Atrial Fibrillation
      Recurrences: Unending Hot Debate.

PMID- 28496674
TI  - Left Atrial Appendage: Extending the Search for New Sources of Atrial
      Fibrillation Triggers.

PMID- 28496675
TI  - Commentary on: Pericardial Fat is Independently Associated with Human Atrial
      Fibrillation by Al Chekakie et al.

PMID- 28496676
TI  - Ablation of Longstanding Persistent Atrial Fibrillation.

PMID- 28496677
TI  - Reducing Ionizing Radiation Associated with Atrial Fibrillation Ablation: An
      Ultrasound-Guided Approach.
AB  - Radiation exposure with cardiac interventional procedures is an emerging concern.
      Patients receiving radiofrequency ablation for atrial fibrillation (AF) still
      routinely undergo pre-ablation computed tomography (CT) scans for definition of
      left atrial and pulmonary vein anatomy, as well as creation of a surrogate
      geometry. In an effort to decrease ionizing radiation associated with AF
      ablation, an ultrasound-guided surrogate geometry approach is proposed as an
      alternative to routine CT imaging. Ten patients underwent AF ablation using
      intracardiac ultrasound for the creation of a surrogate left atrial geometry
      (CartoSound, Biosense Webster, CA); and ten control-cases who had conventional CT
      guided imaging (CartoMerge, Biosense Webster, CA) were matched for age, gender,
      and type of catheter ablation. Sources of radiation included 1) intraprocedural
      fluoroscopy (CartoSound: 151 +/- 43 mGray*cm^2, CartoMerge: 174 +/- 130
      mGray*cm^2; p=0.6) and 2) CT ionizing radiation (CartoSound: 0 mSv, CartoMerge
      9.4 +/- 2.3 mSv/CT scan.) When comparing clinical success rates after a trial of
      previously ineffective anti-arrhythmic drugs, ultrasound-guided AF ablation was
      non-inferior to a CT-guided approach. This potentially obviates the need for CT
      guided imaging, therefore reducing doses of ionizing radiation by nearly 10 mSv
      per AF catheter ablation.

PMID- 28496678
TI  - The Use of Cryoballoon Ablation in Atrial Fibrillation: Simplifying Pulmonary
      Vein Isolation?
AB  - Atrial fibrillation (AF) is certainly the most common arrhythmia encountered in
      clinical practice, reaching epidemic proportions in occidental society. Nowadays,
      transcatheter ablation using radiofrequency (RF) has become a popular technique
      in the treatment of drug-resistant AF. Since ectopic beats originating from the
      pulmonary veins (PVs) have been shown to be the main trigger initiating AF,
      electrical isolation of these venous structures has become the goal when
      performing this procedure.

PMID- 28496679
TI  - Gender and Racial Characteristics of Patients Referred to a Tertiary Atrial
      Fibrillation Center.
AB  - Atrial Fibrillation Centers (AFCs) are becoming increasingly common and are often
      developed at institutions to provide comprehensive evaluation and management for
      patients with atrial fibrillation (AF) including catheter and surgical ablation.
      Studies have shown that women and racial minority patients are less likely to be
      offered aggressive or invasive therapies. The University of Virginia (UVA) AFC
      was opened in 2004. We analyzed data collected during initial visits to our AFC
      from 2004-2008 to determine the gender and racial characteristics of a tertiary
      AFC population. Multivariable regression analysis was used to compare clinical
      characteristics. There were a total of 1664 consecutive initial patient visits.
      Cardiologists referred 61% and primary care physicians referred 37% of patients.
      Twice as many men were referred as women (570 vs. 1094; P<0.0001). Women were
      older (68.0+/-11.9 vs. 62.4+/-13.0 years; P<0.0001) and more symptomatic with
      palpitations (80% vs. 73%; P=0.008), but otherwise were not substantially
      different from men. Our referring physicians treated the majority of both men and
      women with anticoagulant and rate-controlling medications. African American
      patients accounted for 2.8% of AFC initial visits. In contrast, they accounted
      for 7.4% of patients seen for a primary diagnosis of AF at all other UVA
      outpatient clinics (P<0.0001). In conclusion, the demographics of a tertiary AFC
      are different than those of the general population. Women and racial minority
      patients are underrepresented, and the women have few comorbidities and symptoms
      than the known epidemiology would lead us to expect.

PMID- 28496680
TI  - Anticoagulation after Atrial Fibrillation Ablation: Many Blanks to Fill.
AB  - Long-term maintenance of sinus rhythm (SR) after catheter ablation of atrial
      fibrillation (AF) has remained an open issue awaiting further relevant data. It
      is of paramount importance as our everyday decisions on discontinuing
      anticoagulation after ablation rest on the belief in the absence of clinically
      significant asymptomatic AF episodes and constant SR for the rest of the
      patient's life. Both aspects are difficult to ascertain, for the tools of truly
      continuous ECG monitoring are not comfortably applicable, and routine follow-up
      tends to thin out beyond 1 year in asymptomatic patients without apparent
      arrhythmia recurrences.

PMID- 28496681
TI  - Atrail Fibrillation after Carfiac Surgery: Benign or Deserving of Prophylaxis.
AB  - New onset atrial fibrillation (AF) is the commonest complication after cardiac
      surgery affecting around 30% of coronary artery bypass graft (CABG) patients, up
      to 50% of valve surgery patients and as many as 60% of those undergoing combined
      valve and CABG operations. After cardiac transplantation where the native
      pulmonary veins are electrically separated from the donor heart atria the
      incidence is only 11%.

PMID- 28496682
TI  - Left Atrial Volume and Post-Operative Atrial Fibrillation after Aortic Valve
      Replacement.
AB  - Post-operative atrial fibrillation (POAF) after valve surgery is associated with
      increased morbidity and mortality. Risk factors identified in the past to predict
      POAF are of moderate accuracy. We performed a retrospective analysis of 139
      patients undergoing aortic valve replacement for aortic stenosis. Post-operative
      AF occurred in 44% of the patients. In multivariate analysis only left atrial
      volume (LAV) index was a predictor of POAF. A LAV index of >46 cc/m2 predicted
      POAF with a sensitivity and specificity of 92% and 77%. We propose that LAV index
      can be used preoperatively to identify patients at risk for POAF to target
      preventive interventions. Background: Post-operative atrial fibrillation (POAF)
      is common after valve surgery and is associated with increased morbidity and
      mortality. Many of the previously identified predictors of POAF are of moderate
      accuracy. Left atrial volume (LAV) index has been proposed in the past as a
      predictor of POAF in patients undergoing cardiac surgery. In patients with aortic
      stenosis (AS), increased LAV is a marker of severity of stenosis. Hypothesis:
      Left atrial volume index is a very good predictor of POAF in patients undergoing
      aortic valve replacement (AVR) for AS. Methods: We performed a retrospective
      analysis of 139 consecutive patients with no previous atrial fibrillation (AF)
      undergoing AVR for AS in our center. Results: Post-operative AF occurred in 44%
      of patients. Patients with POAF had a longer hospital stay compared to patients
      without (12 vs 8 days; p < 0.001). In univariate analysis, age (p = 0.046),
      aortic valve area (p = 0.005) and LAV index (p < 0.001) were significant
      predictors of POAF. In multivariate analysis only LAV index (R2= 0.58; p < 0.001)
      predicted POAF. A LAV index > 46ml/m2 predicted POAF with a sensitivity and
      specificity of 92% and 77% respectively. Moreover, there was a significant
      increase in the incidence of POAF with increasing quartiles of LAV index,
      supporting causality. Conclusion: Left atrial volume index is an excellent
      predictor of POAF in patients undergoing AVR for AS. It can be used for selecting
      patients who are at a high risk for developing POAF to target preventive
      interventions.

PMID- 28496683
TI  - Atrial Tachycardia Successfully Ablated from the Left Coronary Sinus Cusp of the
      Aorta: An Unusual Site of Origin.
AB  - It has been recognized in the last decade that atrial and ventricular
      tachycardias may arise from the myocardium around the aorta. These tachycardias
      can be ablated from the coronary sinus cusps of the aorta (ASCs) . In some of
      those tachycardias, the site of origin may be epicardial and thus can be ablated
      only through the thin structure of the ASCs. It is important to know how to make
      a diagnosis, map and ablate tachycardias arising from this region.

PMID- 28496684
TI  - Cardiac Image Registration: Rotational Error Correction and Gated Stabilization
      for Cardiac Motion.
AB  - Background: Dynamic motion of the heart due to cardiac and respiratory cycles,
      and rotation from varying patient positions between imaging modalities, can cause
      errors during cardiac image registration. This study used phantom, patient and
      animal models to assess and correct these errors. Methods and Results: Rotational
      errors were identified and corrected using different phantom orientations. ECG
      gated fluoro images were aligned with similarly gated CT images in 9 patients,
      and accuracy assessed during atrial fibrillation (AF) and sinus rhythm. A
      tracking algorithm corrected errors due to respiration; 4 independent observers
      compared 25 respiration sequences to an automated method. Following correction of
      these errors, target registration error was assessed. At 20 mm and 30 mm from the
      phantom model's center point with an in-plane rotation of 8 degrees, measured
      error was 2.94 mm and 5.60 mm, respectively, and the main error identified. A
      priori method accurately predicted ECG location in only 38% (p=0.0003) of 313 R-R
      intervals in AF. A posteriori method accurately gated the ECG during AF and sinus
      rhythm in 97% and 98% of 375 beats evaluated, respectively (p=NS). Tracking
      algorithm for ECG-gated motion compensation was identified as good or fair 96% of
      the time, with no difference between observers and automated method (chi
      square=25; p=NS). Target registration error in phantom and animal models was
      1.75+/-1.03 mm and 0 to 0.5 mm, respectively. Conclusions: Errors during cardiac
      image registration can be identified and corrected. Cardiac image stabilization
      can be achieved using ECG gating and respiration.

PMID- 28496685
TI  - Role of Remote Navigation Systems in AF Ablation.
AB  - During the past decade atrial fibrillation (AF) ablation has developed from being
      an experimental treatment option to an evidence based therapy implemented in
      current guidelines.[1-2] Irrigated radiofrequency current guided ablations remain
      the golden standard of pulmonary vein isolation (PVI) procedures. Although
      practiced more frequently, it remains a demanding procedure requiring skilful
      operators. Novel technologies such as balloon based catheters or remote
      navigation (RN) systems have been developed to overcome the pitfalls of manual
      ablation procedures.

PMID- 28496686
TI  - The Cost of Thromboembolic Events and their Prevention among Patients with Atrial
      Fibrillation.
AB  - Aim: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia.
      People with AF have a significantly increased risk of thromboembolic events,
      including stroke, and the main treatment is therefore aimed at preventing
      thromboembolic events via anticoagulation with warfarin or acetylsalicylic acid.
      However, the development of new anticoagulation treatments has prompted a need to
      know the current cost of AF-related thromboembolic events, for future cost
      effectiveness comparisons with the existing treatments. In this study, we
      estimated the cost of thromboembolic events and their prevention among Swedish AF
      patients in 2010. Methods: The relevant costs were identified, quantified, and
      valued. The complications included were ischaemic and haemorrhagic stroke,
      gastrointestinal bleeding, and other types of major bleeding caused by AF.
      Treatments intended to lower the risk of ischaemic stroke were also included. A
      societal perspective was used, including productivity loss due to morbidity.
      Patients with a CHADS2 score of 1 or higher were included. Results: Among the 9
      340 682 inhabitants of Sweden, there are 118 000 patients with AF and at least
      one more risk factor for stroke, comprising 1.26% of the population. Of these
      patients, 43.3% are treated with warfarin, 28.3% use acetylsalicylic acid, and
      28.3% are assumed to have no anticoagulation treatment. The cost of AF-related
      complications and its prevention in Sweden was estimated at ?437 million for
      2010, corresponding to ?3 712 per AF patient per year. The highest cost was
      caused by stroke, and the second highest by the cost of monitoring the warfarin
      treatment. As the prevalence of AF is expected to increase in the future, AF
      related costs are also expected to rise. Conclusion: Thromboembolic events cause
      high costs. New, easily-administered treatments that could reduce the risk of
      stroke have the potential to be cost-effective.

PMID- 28496687
TI  - Septic Shock due to Implantable Cardiac Defibrillator Related Infection.
AB  - Infection is an important complication of cardiac device implantation. We report
      the case of a 61 year old patient presenting with septic shock caused by cardiac
      device infection (CDI) three-weeks after device implantation. At initial
      presentation, there was an absence of both localising signs and echocardiographic
      evidence of CDI. Later, Staphylococcus aureus was cultured from blood and the pre
      pectoral pocket. 48 hours after admission the device and leads were explanted in
      theatre by simple traction. Despite appropriate antibiotics and full supportive
      care (including haemofiltration, ventilation and inotropic support), the patient
      died on day six. Cardiac device infection may present with septic shock in the
      absence of localising features. A high index of suspicion is required,
      particularly for early CDI.

PMID- 28496688
TI  - Atrial Fibrillation in the Wolff-Parkinson-White Syndrome.
AB  - Since the advent of catheter ablation for atrial fibrillation (AF) aiming the
      pulmonary veins a few years ago, there has been an overwhelming interest and a
      dramatic increase in AF investigation. AF has a different dimension in the
      context of the Wolff-Parkinson-White (WPW) syndrome. Indeed, AF may be a
      nightmare in a young person that has an accessory pathway (AP) with fast
      anterograde conduction. It may be life-threatening if an extremely rapid
      ventricular response develops degenerating into ventricular fibrillation.
      Therefore, it is very important to know the mechanisms involved in the
      development of AF in the WPW syndrome. There are several possible mechanisms that
      may be involved in the development of AF in the WPW syndrome, namely, spontaneous
      degeneration of atrioventricular reciprocating tachycardia into AF, the
      electrophysiological properties of the AP, the effects of AP on atrial
      architecture, and intrinsic atrial muscle vulnerability. Focal activity, multiple
      reentrant wavelets, and macroreentry have all been implicated in AF, perhaps
      under the further influence of the autonomic nervous system. AF can also be
      initiated by ectopic beats originating from the pulmonary veins, and elsewhere.
      Several studies demonstrated a decrease incidence of AF after successful
      elimination of the AP, suggesting that the AP itself may play an important role
      in the initiation of AF. However, since AF still occurs in some patients with the
      WPW syndrome even after successful ablation of the AP, there should be other
      mechanisms responsible for the development of AF in the WPW syndrome. There is a
      clear evidence of an underlying atrial muscle disease in patients with the WPW
      syndrome. Atrial myocardial vulnerability has been studied performing an atrial
      endocardial catheter mapping during sinus rhythm, and analizing the recorded
      abnormal atrial electrograms. This review analizes the available data on this
      singular setting since AF has a reserved prognostic significance in patients with
      the WPW syndrome, and has an unusually high incidence in the absence of any
      clinical evidence of organic heart disease.

PMID- 28496689
TI  - Computed Tomography Imaging in Atrial Fibrillation Ablation.
AB  - Atrial fibrillation (AF) is the most common supraventricular arrhythmia in adults
      and catheter ablation has increasingly become the therapy of choice for
      symptomatic, recurrent, drug refractory AF. The purpose of this review is to
      evaluate the utility of computed tomography (CT) imaging in guiding
      radiofrequency catheter ablation (RFCA), as well as highlight the additional
      radiographic and functional anatomic data provided by CT in comparison to
      alternative radiographic modalities.

PMID- 28496690
TI  - Preoperative Statin use is not Associated with a Reduced Risk of Atrial
      Fibrillation After Cardiac Surgery.
AB  - Introduction: Postoperative atrial fibrillation (POAF) is prevalent after cardiac
      surgery and associated with significant morbidity and costs. Statins are commonly
      used in this population and may be a preventative strategy for PAOF. We wished to
      examine the effect of preoperative statin use on the risk of POAF after cardiac
      surgery. Methods: A retrospective, observational study was conducted using data
      from 489 adult patients who underwent cardiac surgery at a single institution.
      Univariate analyses and unconditional logistic regression were used to determine
      the impact of preoperative statin use on the probability of developing POAF,
      while controlling for the baseline risk of POAF and the use of amiodarone
      prophylaxis (AMP). A baseline risk index was calculated for each patient using a
      previously validated model. Patients with chronic atrial fibrillation or missing
      data were excluded. Results: Mean patient age was 63 (SD=13) years, 73% were
      male, 68% underwent isolated coronary artery bypass grafting, 16% underwent
      isolated valve surgery, with 13% underwent combined CABG and valve surgeries, and
      3% underwent other forms of cardiac surgery. POAF occurred in 27% of patients
      receiving statins and 24% of those not receiving statins (p=0.3792). After
      controlling for baseline risk of POAF and the use of AMP, we found that
      preoperative statins were not associated with reductions in POAF (OR=1.19,
      95%CI=0.782-1.822, p=0.4118). Conclusions: Multiple factors impact the
      development of POAF after cardiac surgery including patient demographics,
      comorbidities, surgical type, and concomitant medications. In this study, after
      adjustment for these factors the preoperative use of statins did not
      significantly influence the development of POAF.

PMID- 28496691
TI  - Comments on: Clinical Significance of Early Recurrences of Atrial Tachycardia
      After Atrial Fibrillation Ablation by Choi JI et al.

PMID- 28496692
TI  - Head Up Tilt Testing: An Appraisal of Its Current Role in the Management of
      Patients with Syncope.
AB  - Head up tilt testing (HTT) is now commonly used to investigate otherwise
      unexplained syncope and presyncope. This test has been used for over 20 years
      primarily to diagnose neurally mediated syncope, but HTT's exact role in the
      diagnostic process remains uncertain. Recognized limitations include poor
      reproducibility, lack of prognostic role, and insufficient randomized studies to
      guide therapeutic choice. In this review, we describe the indications and methods
      recommended by present guidelines on utilizing HTT. In addition, present
      criticisms and limitations of this test, along with future perspectives, are
      outlined.

PMID- 28496693
TI  - Ablation of Atrial Fibrillation in the Elderly: Current Evidence and Evolving
      Trends.
AB  - Management of atrial fibrillation in the elderly presents unique challenges,
      including deciding upon the best treatment strategy: rate control versus rhythm
      control. The decision to pursue one treatment strategy over another is based on
      understanding the underlying disorder: symptomatology from atrial fibrillation
      itself versus symptoms due to a rapid ventricular response from atrial
      fibrillation. The ablation strategies for the treatment of atrial fibrillation
      include atrioventricular junction ablation and pulmonary vein isolation. This
      review discusses the data on ablation of atrial fibrillation in the elderly, with
      an emphasis on issues regarding safety and efficacy in this population.

PMID- 28496694
TI  - Do Statins Reduce Atrial Fibrillation After Coronary Artery Bypass Grafting?
AB  - Background: Atrial Fibrillation (AF) is a common postoperative complication after
      coronary artery bypass grafting. There is contradictory evidence as to whether
      pre-operative statin use lowers the incidence of postoperative AF. This study
      aimed to assess whether pre operative statin therapy prevents the post-operative
      AF. Methods: In this retrospective cohort study we used a propensity score
      matching analysis to evaluate the effect of preoperative treatment with statins
      on postoperative atrial fibrillation. There were 427 matched pairs of patients.
      Primary outcome was the incidence of postoperative AF. Secondary outcomes were 30
      day mortality, stroke, myocardial infarction and length of hospital stay.
      Results: The incidence of postoperative AF was not different in the statin users
      compared with the nonusers (123, 28.1%, versus 127, 29.7%, respectively; p =
      0.764). The 30 day mortality (6, 1.4%, versus 8, 1.9%; p = 0.590), stroke (10,
      2.3%, versus 8, 1.9%; p = 0.634), myocardial infarction (2, 0.5%, versus 0, 0.0%;
      p = 0.499) and length of hospital stay in days (11.8 +/- 9.0, versus 11.9 +/-
      9.3; p = 0.544) did not differ significantly between the two groups. Conclusions:
      In a propensity-matched cohort of patients undergoing coronary bypass surgery, we
      could not demonstrate that preoperative statins were protective for the
      development of post operative atrial fibrillation.

PMID- 28496695
TI  - Quinidine for Pharmacological Cardioversion of Long-lasting Atrial Fibrillation.
AB  - Background: In the daily clinical practice, patients with atrial fibrillation
      (AF) lasting more than 48h (or not datable at all) are not uncommon. In long
      lasting AF changes in electrophysiological features (electrical remodeling) can
      occur, resulting in a loss of sensibility to most antiarrhythmic drugs. There is
      strong evidence that the main mechanism involved in electrical remodeling is a
      global shortening in refractory period. To assess safety and efficacy of
      quinidine in pharmacological cardioversion of long-lasting AF, compared with
      propafenone and amiodarone. Methods and Results: Ninety consecutive patients with
      AF lasting more than 6 weeks were randomized to amiodarone (5mg?kg bolus, then
      15mg?kg in 24h) , propafenone (2 mg?kg bolus then 0.007mg?kg for 2h), and
      quinidine (275mg of quinidine arabogalattan sulphate per os every 2h for 8h
      maximum) for pharmacologic cardioversion. All patients had been previously
      treated with adequate oral anticoagulation and had been submitted to
      transthoracic echocardiogram. The 3 groups of patients did not differ for
      baseline and echocardiographic characteristics. Sinus rhythm was restored in 16
      patients treated with quinidine (53%), compared with 6 patients (20%) in the
      amiodarone and propafenone groups (p<0.01). No major adverse effect was reported
      during the treatment. Conclusions: Quinidine seems to be safe and effective in
      pharmacological cardioversion of long-lasting AF.

PMID- 28496696
TI  - Irrigated-Tip Magnetic Catheter Ablation Of AF: ALong-Term Prospective Study In
      130 Patients.

PMID- 28496697
TI  - Association of Left Atrial Fibrosis Detected by Delayed Enhancement Magnetic
      Resonance Imaging and Risk of Stroke in Patients with Atrial Fibrillation.

PMID- 28496698
TI  - Cardiac Resynchronization Therapy and Atrial Fibrillation.
AB  - Cardiac resynchronization therapy (CRT) is an important advance for the treatment
      of end--stage heart failure (HF). About 15-50% of HF is complicated by atrial
      fibrillation (AF) and associated with worsened outcomes. Meta-analyses from
      observational studies suggest that patients with AF derive similar benefits to
      CRT as patients in sinus rhythm (SR). The presence of AF, however, may interfere
      with optimal delivery of CRT due to competition with biventricular (BiV) capture
      by conducted beats. Atrioventricular junction (AVJ) ablation with permanent
      pacing eliminates interference by conducted beats and provides complete BiV
      capture. Catheter ablation of AF is an alternative to antiarrhythmic drugs to
      maintain sinus rhythm in patients with AF and HF. Randomized trial comparing
      catheter ablation, AVJ ablation and pharmacologic therapy are needed.

PMID- 28496699
TI  - Complications of Radiofrequency Catheter Ablation for Atrial Fibrillation.
AB  - Radiofrequency catheter ablation (RFA) has evolved as an effective treatment
      modality in patients with atrial fibrillation (AF). However, complication rates
      associated with RFA of AF have been cited in the range of 3.5 - 5% with the
      majority consisting of cardiac tamponade, vascular complications, and
      thromboembolic phenomena. In this review, the complications of AF ablation will
      be discussed along with associated clinical management strategies.

PMID- 28496700
TI  - IntravenousCorticosteroid Use Is Associated With Reduced Early Recurrence of
      Atrial Fibrillation Immediately Following Radiofrequency Catheter Ablation.
AB  - Background: Early recurrence of atrial fibrillation (ERAF) occurs in up to 40% of
      patients after radiofrequency catheter ablation for atrial fibrillation (RFCA),
      increasing hospital stay, need for anti-arrhythmic medications (AADs) and
      cardioversion, and, possibly, the risk of future AF. It has been postulated that
      inflammation plays a key role in developing ERAF. Short term postoperative use of
      corticosteroids to reduce ERAF post-RFCA has not been vigorously studied.
      Methods: This was a case-control study of consecutive patients undergoing RFCA
      for the management of AF at a single-institution. RFCA was performed by a single
      operator from October 2005 through July 2009. Patients receiving intravenous
      corticosteroids immediately following the ablation and for 48 hours (6 doses)
      constituted the treatment group. Controls received no intravenous corticosteroids
      during their hospitalization. All other management strategies were similar
      between the 2 groups, including the administration of AADs post- operatively. All
      patients had continuous electrocardiographic monitoring throughout their
      hospitalization. Multivariable logistic regression analysis was used to determine
      the impact of intravenous corticosteroids on ERAF defined as any AF>10 minutes
      during hospitalization. Results: A total of 68 patients undergoing RFCA for the
      management of AF were included in this analysis. The overall ERAF rate,
      irrespective of intravenous corticosteroid use, was 23.5%. The administration of
      intravenous corticosteroids (n=37; mean+/-SD dexamethasone mean dose 11.9+/-4.6
      mg/day; range 4-16 mg/day) was associated with an 82% reduction in patients' odds
      of ERAF (adjusted odds ratio; 0.18, 95% confidence interval [CI] 0.04 to 0.78)
      compared with those who did not receive corticosteroids (n=31). A dose-response
      effect was also observed, with a 17% reduction in ERAF odds for each
      dexamethasone mg-equivalent administered (adjusted odds ratio; 0.83, 95%CI 0.73
      to 0.96). Conclusions: The use of intravenous corticosteroids was associated with
      a dose-dependent reduction in the odds of developing ERAF after RFCA for the
      management of AF.

PMID- 28496701
TI  - Atrial Fibrillation After Lung Transplantation: Incidence, Predictors and Long
      Term Implications.
AB  - Background: Little is known about the frequency of, risk factors predisposing to,
      and long-term impact of post-operative atrial fibrillation (AF) after lung
      transplantation. Methods: A prospectively collected registry of 167 consecutive
      patients who underwent single or bilateral lung transplantation at the University
      of Minnesota Medical Center from January 1st, 2004 to December 30th, 2008 was
      reviewed. Post-operative AF was confirmed by review of electrocardiograms by two
      cardiologists. Kaplan-Meier survival curves were constructed to determine the
      impact of new onset AF on long-term survival. Results: The mean age (+/-SD) of
      the population was 55 +/- 11 years and 52% were male. A total of 48 patients
      (28%) developed AF in the postoperative period. Predictors of postoperative AF in
      multivariate analysis included: age (per decade) Odds Ratio (OR): 1.61, 95%
      confidence interval (CI) 1.10-2.34, p=0.01, postoperative thromboembolic disease
      OR: 9.73 (95% CI: 2.16-43.81, p<0.01, and postoperative pericarditis OR: 3.57,
      (95% CI: 1.38-9.22, p < 0.01). Of the 48 patients who developed post-operative
      AF, 41 were discharged in sinus rhythm (SR). Survival among patients who were
      discharged in AF was significantly lower when compared to patients discharged in
      SR (HR: 0.08; 0.01-0.43, p<0.05). Conclusions: Postoperative AF is common after
      lung transplant. Increased age, postoperative thromboembolic disease, and
      pericarditis are independent predictors of postoperative AF. Persistence of AF at
      the time of discharge is an identifier of decreased survival.

PMID- 28496702
TI  - Neuropsychological Decline After Catheter Ablation of Atrial Fibrillation.

PMID- 28496703
TI  - Atrial Coronary Arteries: Anatomy And Atrial Perfusion Territories.
AB  - Coronary anatomy has traditionally focused on ventricular circulation. This is
      largely due to the extent to which coronary artery disease contributes to
      ischemic heart disease through ventricular myocardial damage. Atrial fibrillation
      and other tachyarrhythmias that involve the atria, however, remain a major cause
      of morbidity and mortality. In order to increase mechanistic research and
      therapeutic interventional procedures for diseases of the atria, an optimal
      knowledge of atrial anatomy is necessary. While substantial clarity exists
      regarding the distribution of nerve terminals and the organization of muscle
      bundles, the anatomy of coronary atrial circulation remains understudied.
      Historically, the high anatomical variability of atrial coronary branches led to
      unstandardized nomenclature in the literature. In this review, we delineate the
      anatomic courses of key atrial coronary branches and their perfusion territories,
      clarify their nomenclature, and propose unifying anatomical concepts of atrial
      circulation that we believe to be critical to the success of modern
      electrophysiologic and surgical procedures.

PMID- 28496704
TI  - Metformin associated Atrial Fibrillation - A Case Report.

PMID- 28496705
TI  - Role of Echocardiography in Atrial Fibrillation Ablation.
AB  - Radiofrequency catheter ablation is an increasingly adopted strategy for
      difficult-to-manage patients with atrial fibrillation. Echocardiography is the
      key imaging modality to assess left atrialstructure and function. In this review,
      the role of echocardiography in atrial fibrillation ablationbefore, during and
      after ablation is discussed. Currently established roles of echocardiography
      inpatient selection pre-ablation and peri-procedural guidance, as well as newer
      echocardiographic techniques including the assessment of atrial mechanics are
      reviewed in the context of atrial fibrillation ablation.

PMID- 28496706
TI  - Renin-Angiotensin System and AtrialFibrillation:Understanding the Connection.
AB  - Atrial fibrillation (AF) arises as a result of a complex interaction of triggers,
      perpetuators and the substrate. The recurrence of AF may be partially related to
      a biologic phenomenon known as remodeling, in which the electrical, mechanical,
      and structural properties of the atrial tissue and cardiac cells are
      progressively altered,creating a more favorable substrate. Atrial remodeling is
      in part a consequence of arrhythmia itself. Therefore,to prevent and to treat AF,
      much attention has been directed to upstream therapies to alter the arrhythmia
      substrate and to reduce atrial remodeling. The renin-angiotensin-aldosterone
      system (RAAS) plays a keyrole in these strategies. In this review we analyze the
      experimental and clinical evidence regarding the efficacy of RAAS inhibitors in
      AF treatment. In the primary prevention of AF, meta-analyses have shown that risk
      of new-onset AF in patients with congestive heart failure and left ventricular
      dysfunction is reduced by RAAS inhibitors, whereas in hypertensive and post
      myocardial infarction patients, the results are less evident. In the secondary
      prevention of AF, some large, prospective, randomized, placebo-controlled
      studieswith angiotensin II-receptor blockers returned negative results.
      Unfortunately, the approach of using RAASinhibitors as antiarrhythmic drugs to
      prevent both new-onset and recurrent AF is in decline because negativetrial
      results are accumulating, with the exception of the results in patients with
      congestive heart failure.

PMID- 28496707
TI  - Stretch and Inflammation- Their Relation to Fractionation of Electrograms in
      Atrial Fibrillation.
AB  - BACKGROUND: Inflammatory markers (IM) are elevated in atrial fibrillation (AF).
      However the relation of IM to substrate modificationinAF remains unclear.We
      sought to assess the relationship of IM to fractio ated atrial electrogram (FAE)
      in patients undergoing AF ablation. METHODS: At baseline, left atrial (LA)
      pressure was recorded and peripheral blood was tested for IM. FAE mapping
      wasperformed before and after circumferential pulmonary vein and linear ablation
      (CPVA-L) and followed by FAEablation. Image processing was used to define the FAE
      areas. AF cycle-length (AFCL) was compared between baseline and after ablations
      from left atrial electrode. RESULTS: Older patients had higher cytokine levels.
      FAE area at baseline (secondary FAE) negatively correlated with the levels of
      interleukin-6 (IL-6, R2= -0.97 and p=0.03) and interleukin-12p70 (IL-12p70, R2= 
      0.97 and p=0.03). In addition, a significant reduction in FAE area and index
      occurred after CPVA-L (p=0.0001). FAE after CPVA-L (primary FAE) correlated with
      left atrial pressure (LAP), [R2 0.5, (p=0.02)]. The AFCL (in msec) increased from
      135 +/- 41 to 149.5+30 (p=ns) after CPVA-L and further increased to 191.5 +/- 60
      (p=0.007) after FAE ablation. CONCLUSIONS: There is a negative correlation of IL
      6 and IL-12p70 to baseline FAE, suggesting a possibility of sequestration of
      these cytokines in left atrium. CPVA-L ablation reduces FAE area which when
      ablated increases AFCL, suggesting that these areas likely represent primary
      fragmentation due to rotors, triggered by atrial stretch as seen by the relation
      of left atrial pressure and post CPVA-L FAE.

PMID- 28496708
TI  - Risk Alteration for Atrial Fibrillation with DifferentAntihypertensive Drugs.
AB  - A large percentage of patients with hypertension suffer from atrial fibrillation
      (AF). The concomitance of both conditions in the same patient markedly increases
      cardiovascular risk. Therefore, prevention of new-onset AF in hypertensive
      population should be a relevant target. High blood pressure promotes structural
      and electrophysiological changes in the heart that promote the develop- ment of
      AF. Thus, the most important therapeutic approach to prevent incident AF in
      hypertensive population is to reduce blood pressure values to recommended goals.
      However, in specific conditions, some antihypertensive agents may provide
      additional benefits beyond blood pressure reduction, such as in hypertension with
      left ven- tricular hypertrophy with renin angiotensin system blockade. On the
      other hand, in patients with hypertension and permanent AF, beta blockers and
      nondihydropiridine calcium antagonists (verapamil and diltiazem) play an
      important role. Antihypertensive agents may provide beneficial effects on
      incident AF, regardless of the presence of hyperten- sion. Thus, renin
      angiotensin system inhibitors may reduce new-onset AF in patients with heart
      failure or after the cardioversion of persistent AF. On the other hand, the
      preoperative administration of beta blockers may re- duce the incidence of
      postoperative AF in some patients. In this manuscript, the available evidence
      about the effects of different antihypertensive agents on new-onset AF in
      different populations is reviewed.

PMID- 28496709
TI  - Atrium-Atrioventricular Node Conduction Block during Catheter Ablation of
      Persistent Atrial Fibrillation.
AB  - Previous studies have suggested that fibrillatory substrates are widely
      distributed in both atria in patients with persistent atrial fibrillation.
      Extensive bi-atrial ablation has been increasingly performed to improve the
      clinical outcomes; however, this may adversely affect the intra-atrial conduction
      during sinus rhythm. The worst con- sequence of an intra-atrial conduction
      disturbance is conduction block between the atrium and atrioventricular node.
      There have been a few case reports on this complication, which suggest that the
      conduction block may occur more. This review aimed to describe the risk factors
      and method of prevention of atrium-atrioventric-ular node conduction block.

PMID- 28496710
TI  - Prevention of Stroke in Patients With Atrial Fibrillation.
AB  - The presence of atrial fibrillation (AF) increases the risk of stroke, especially
      in patients with risk factors as outlined by the CHADS2 and CHA2DS2-VASc scoring
      systems. Although warfarin can reduce stroke rates by over 65%, only 55% of
      patients, in the USA, who should be on warfarin for AF and stroke prevention are
      taking the drug due to the need of INR monitoring, difficulties in maintaining a
      therapeutic INR in the therapeutic range and dietary and drug interactions.
      Dabigatran, an oral direct thrombin inhibitor and rivaroxaban and apixaban,
      factor Xa inhibitors, have demonstrated efficacy in reducing stroke in large
      clinical trials. These novel anticoagulants will change the therapeutic landscape
      since patients will be able to prevent stroke with a lower risk of intracranial
      hemorrhage and without the need for INR monitoring and less drug-dietary
      interactions.

PMID- 28496712
TI  - The Concept of "Burden" in Atrial Fibrillation.
AB  - Over the last decade or so the term "burden" has become frequently encountered in
      manuscripts discussing atrial fibrillation (AF). AF "burden" is perhaps most
      commonly encountered in the electrophysiological context - the amount of time the
      patient is in AF out of the total monitored time (i.e., the percent of time one
      is in AF). However, "burden" in AF may also be used in other contexts, which we
      characterize below as "disease burden", "clinical burden," "economic burden."
      Over the course of the disease progression and its therapy, such "burdens" may
      change, and may do so in parallel with each other or in opposite directions. This
      manuscript explores these various concepts of AF "burden" so as to emphasize to
      authors and readers that when using the term, its meaning must be made clear.

PMID- 28496711
TI  - Catheter Ablation of Atrial Fibrillation in Overweight and Obese Patients.
AB  - Obesity has reached epidemic proportions, and is associated with increased all
      cause mortality. Atrial fibrillation(AF), the most common sustained arrhythmia in
      the clinical practice, is associated with an increased longterm risk of stroke,
      heart failure, and all-cause mortality. Accumulating data points out to an
      indispensable role of inflammation in both obesity and AF. Recent studies have
      documented an increasing risk of AF with increasing body mass index (BMI). The
      pathophysiological alterations associated with overweight and obesity lead to
      atrial stretch and atrial enlargement creating the substrate for AF development.
      Catheter ablation of AF has been widely accepted as an important therapeutic
      modality for the treatment of patients with symptomatic,drug-refractory AF.
      Previous studies assessing the impact of BMI on AF catheter ablation outcomes
      have given conflicting data. Given that overweight and obesity, as defined by
      BMI, and AF are closely linked,the present review sought to investigate the
      impact of BMI on the efficacy and safety of AF catheter ablation.

PMID- 28496713
TI  - A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation.
AB  - Cardiac hypertrophy is a major risk factor for the development of atrial
      fibrillation (AF). However, there are few animal models of AF associated with
      cardiac hypertrophy. In this study, we describe the in vivo electrophysiological
      characteristics and histopathology of a mouse model of cardiac hypertrophy that
      develops AF. Myostatin is a well-known negative regulator of skeletal muscle
      growth that was recently found to additionally regulate cardiac muscle growth.
      Using cardiac-specific expression of the inhibitory myostatin pro-peptide, we
      generated transgenic (TG) mice with dominant-negative regulation of MSTN (DN
      MSTN). One line (DN-MSTN TG13) displayed ventricular hypertrophy, as well as
      spontaneous AF on the surface electrocardiogram (ECG), and was further evaluated.
      DN-MSTN TG13 had normal systolic function, but displayed atrial enlargement on
      cardiac MRI, as well as atrial fibrosis histologically. Baseline ECG revealed an
      increased P wave duration and QRS interval compared with wild-type littermate
      (WT) mice. Seven of 19 DN-MSTN TG13 mice had spontaneous or inducible AF, while
      none of the WT mice had atrial arrhythmias (p<0.05). Connexin40 (Cx40) was
      decreased in DN-MSTN TG13 mice, even in the absence of AF or significant atrial
      fibrosis, raising the possibility that MSTN signaling may play a role in Cx40
      down-regulation and the development of AF in this mouse model. In conclusion, DN
      MSTN TG13 mice represent a novel model of AF, in which molecular changes
      including an initial loss of Cx40 are noted prior to fibrosis and the development
      of atrial arrhythmias.

PMID- 28496714
TI  - South Asians are Under-Represented in a Clinic Treating Atrial Fibrillation in a
      Multicultural City in the UK.
AB  - The Leeds rapid access atrial fibrillation (AF) clinic was set up to streamline
      and standardise management of patients with newly diagnosed AF. Anecdotal
      evidence suggests that there is under-representation of south Asians in these
      clinics.All patient attendances between June 2007 and June 2011 were documented
      and combined with ethnicity data from patient administration records. Local
      population demographics for 2009 were obtained from the office of national
      statistics. This was used to estimate the expected prevalence of AF across the
      different ethnic groups in Leeds taking age into account. One thousand two
      hundred and ten patients were referred. The study sample included 992 patients,
      and the number of south Asians attending was 88% less than expected (Chi squared
      analysis; p<0.0001). These results suggest that there is an under-representation
      of south Asians in a large centre that serves a cosmopolitan population.
      Potential reasons for this discrepancy including barriers to accessing treatment
      for this population or a lower prevalence of AF in south Asians due to an as yet
      unidentified genetic factor.

PMID- 28496715
TI  - Role of Echocardiography in the Management and Prognosis of Atrial Fibrillation.
AB  - Echocardiography plays a longstanding and vital role in the management of atrial
      fibrillation (AF). Advances in 2D imaging, Doppler echocardiography and strain
      imaging have all contributed to major progress in AF treatment.
      Echocardiographically measured left atrial (LA) volume is a powerful predictor of
      maintenance of sinus rhythm following cardioversion as well as risk of thrombus
      formation and thromboembolism. Doppler derived parameters of atrial mechanical
      function including atrial ejection force provide related prognostic information.
      Transesophageal echocardiocardiograpy (TEE) guided cardioversion of AF allows for
      rapid conversion to sinus rhythm without prolonged oral anticoagulation, and TEE
      serves as a useful tool during catheter ablation of AF and atrial flutter. Newer
      measures derived from speckle tracking offer great promise in further improving
      the care of patients with AF.

PMID- 28496716
TI  - Left Atrial Diastolic Dysfunction following Catheter Ablation of Atrial
      Fibrillation.
AB  - Radiofrequency catheter ablation (RFCA)-induced thermal injury may cause and/or
      worsen left atrial (LA) diastolic dysfunction leading to pulmonary hypertension
      and heart failure in patients with atrial fibrillation (AF), the incidence of
      which is probably more common than is generally realized. Biplane 2-dimensional
      echocardiography coupled with tissue Doppler (velocity) imaging and Doppler
      derived strain (rate) imaging can be applied to provide quantitative assessment
      of the LA function (both systolic and diastolic) relative to pulmonary venous
      circulation and left ventricular function. Information so obtained is useful for
      guiding follow-up management of patients undergoing RFCA of AF.

PMID- 28496717
TI  - Necessity of Repeat Ablations to Eliminate Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most common human arrhythmia and leads to
      increased morbidity and mortality. Because of demographic changes, the prevalence
      of AF will increase in the next decades, requiring better primary prevention
      strategies and better treatment options. In 1998, Haissaguerre et al. described
      triggering foci in the pulmonary veins (PV) as the prevailing pathophysiological
      initiator of paroxysmal AF. Since then, multiple studies have been conducted
      using the technique of pulmonary vein isolation (PVI) to eliminate AF. In short
      term follow-up, success rates of 60-75% in patients with paroxysmal AF are
      reached, with significantly worse results in persistent AF of approximately 50%.
      Due to arrhythmia recurrence, multiple procedures are often necessary, especially
      in patients with persistent AF, to achieve these results. It is supposed that the
      cause of arrhythmia recurrence is pulmonary vein reconnection in patients with
      paroxysmal AF, and insufficient substrate modification or new substrate
      development in patients with persistent AF. Future techniques like contact force
      control might improve lesion formation leading to improved PVI and substrate
      modification.

PMID- 28496718
TI  - Adverse Outcomes from Atrial Fibrillation;Mechanisms, Risks, and Insights Learned
      from Therapeutic Options.
AB  - Atrial Fibrillation (AF) continues to increase in prevalence and its'
      consequences and disease associations have a great impact on multiple aspects of
      medical practice. As such, making preventive strategies to minimize risk of the
      arrhythmia and its' complications are paramount to improve quality of life,
      mortality, and limit medical resource utilization. To the extent that AF
      independently impacts adverse cardiovascular outcomes, this review article will
      focus on these outcomes, in particular heart failure (HF), stroke, and mortality,
      and discuss contemporary strategies for treatment. Conclusions: AF has a marked
      deleterious impact on the lives of patients. This impact can be accelerated when
      other cardiac diseases coexist. Although rhythm control strategies have been an
      intriguing tool to reverse or minimize the adverse outcomes associate with AF,
      they have largely been unsuccessful. In general, failures of currently available
      AADs to improve survival are due to failure of the drug to maintain sinus rhythm
      and presence of drug toxicities. Early data with ablation approaches are
      favorable and support rhythm control strategies to minimize long-term risks
      associated with AF. However, most of the data stem from observational analysis or
      small randomized trials. Large randomized prospective trials will ultimately
      define the role of catheter ablation in the management of AF patients.

PMID- 28496719
TI  - Collateral Damage During Ablation of Atrial Fibrillation - Lessons Learnt in the
      Past Decade.

PMID- 28496720
TI  - Age as a Risk factor for Atrial Fibrillation and Flutter after Coronary Artery
      Bypass Grafting.

PMID- 28496721
TI  - Phrenic Nerve and Esophageal Injury During Catheter Ablation of Atrial
      Fibrillation.
AB  - Atrial fibrillation is a common cardiac arrhythmia with rapid and irregular
      atrial activity. Although radiofrequency catheter ablation of atrial fibrillation
      has became an established treatment for the management of symptomatic drug
      refractory patients in the past decade, several complications due to the
      procedure have been reported. The purpose of this review article is to describe
      the collateral damage from catheter ablation of atrial fibrillation.

PMID- 28496722
TI  - Predictors of Recurrence After Catheter Ablation of Persistent Atrial
      Fibrillation.
AB  - Catheter ablation of atrial fibrillation (AF) has been increasingly used to treat
      symptomatic patients.Within the last years a growing interest in ablation of
      persistent AF forms has evolved.Factors that may influence outcome of these
      procedures to treat persistent AF may be patient-specific (pre
      procedural),procedure-related or may involve different post-ablation followup
      strategies. In this review potential factors predicting recurrence of AF after
      ablation of persistent AF have been evaluated.In essence, data is limited mostly
      due to incongruent definitions of persistent AF.Left atrial dimensions, duration
      of continuous AF and AF cycle length may be patient-specific predictors of
      outcome. Intra-procedural parameters involved in recurrence prediction may be
      extent of ablation (effective pulmonary vein isolation appears mandatory) and
      termination of AF during ablation. Timing and number of cardioversion if
      persistent AF recurs may predict outcome, as well. Many studies have identified
      strators for higher recurrence rates in rather small patient groups and need to
      be further evaluated in larger patient collectives.

PMID- 28496723
TI  - Conversion of Persistent Atrial Fibrillation After Radiofrequency Ablation by
      Ibutilide.
AB  - Ablation of peristent AF remains challenging with questions unanswered about what
      the ideal next step after pulmonary venous isolation should be. Ibutilide is a
      highly effective class III agent for cardioversion of acute-onset atrial flutter
      and fibrillation, with limited clinical use due to risks of ventricular pro
      arrhythmias. However, results from the on-going MAGIC-AF trial may re-invigorate
      its role in clinical electrophysiology as an invaluable adjunct to facilitate
      controlled substrate modification during ablation of persistent AF.

PMID- 28496724
TI  - Non-interventional Management of Symptomatic Pulmonary Vein Occlusion after
      Radiofrequency Ablation for Atrial Fibrillation.
AB  - Pulmonary vein occlusion (PVO) after atrial fibrillation ablation is often highly
      symptomatic. In cases with a clear target, balloon angioplasty and stenting can
      be successful. In the absence of such a target, surgical lobectomy has been
      reported as a treatment option, but the natural history of physiological
      adaptation may outweigh the risks of invasive therapies and a non-invasive
      strategy is valid in these situations. We present a case of highly symptomatic
      PVO managed non-invasively, with complete symptom resolution and return to high
      intensity exercise. Catheter intervention may not always be possible in the
      absence of a target vessel, and lobectomy may not be necessary to manage PVO.

PMID- 28496725
TI  - Preventative Measures of Stroke in Patients With Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia and is
      associated with increased morbidity and mortality due to stroke and thrombo
      embolism. In patients with AF, strokes are usually more severe, resulting in
      longer hospital stays, worse disability and considerable healthcare costs. The
      prevention of stroke therefore is crucial in the management of AF. Stroke risk
      stratification tools can be used to determine patients at higher risk of stroke,
      and if no contraindications are present oral anticoagulation (OAC) therapy can be
      initiated. Despite the strong evidence for the benefit of OAC in stroke
      prevention in patients with AF, the use of thromboprophylaxis remains inadequate.
      The key measures to prevent stroke in patients with AF include: adequate stroke
      risk assessment and thrombo-prophylaxis; prompt initiation of OAC and avoidance
      of interruptions; earlier detection of AF; and education to overcome the under
      usage of OAC in elderly patients.

PMID- 28496726
TI  - Outcome of Patients Discharged after their First Detected Episode of Atrial
      Fibrillation.
AB  - Atrial fibrillation (AF) is the most frequent supraventricular arrhythmia with an
      approximative prevalence of 1 % in the general population and above 6 % in the
      elderly. After a first AF diagnosis, the hospitalization rate is markedly
      increased. Management of a first AF episode is different depending on the
      clinical status of patients. Practical guidelines developed in collaboration with
      the European Heart Rhythm Association and the Heart Rhythm Society are available
      for the management of these patients. A four-step decisional scheme must be
      followed in the management of a first recent AF episode: need for a short- and
      long-term anticoagulation, define a rythmologic strategy (rhythm or rate
      control), select the weapon (drug, device or ablation) and reconsider the
      strategy if needed. After a first uncomplicated paroxysmal AF episode, guidelines
      recommend that prescription of antiarrhythmics must be avoided and
      anticoagulation is optional. After a first persistent AF episode, guidelines
      recommend to either respect or reduce the arrhythmia. Prescription of
      antiarrhythmics and anticoagulation is also optional depending on the patient?s
      condition. In case of the AF reduction decision, anticoagulation must be tailored
      preliminary to this reduction. AF recurrence rate varies depending on the
      patient?s condition, and the risk of stroke assessed by the CHA2DS2-VASc score
      might be similarly considered for both paroxysmal and persistent AF.

PMID- 28496727
TI  - Risk Factors for the Development of Atrial Fibrillation in HIV Infected Patients.
AB  - Background: Patients with Human Immunodeficiency Virus (HIV) have an array of
      multi-organ involvement, including cardiovascular disease. CD4 count is one of
      the best parameters to monitor the severity of HIV disease. The arrythmogenic
      potential of HIV disease has not been well defined. The aim of the study is to
      establish whether an association between the severity of HIV and atrial
      fibrillation (AF) exists. Methods: Out of a retrospective cohort of 780 HIV
      patients from January 2006 to December 2008, 40 patients were selected that
      developed AF during this period .The age and sex matched controls (n=40) were
      selected for comparison. The comparison between both groups was done using
      Fischer Exact Test. Bivariate and multivariate analysis was also performed to
      analyze the results. Results: The data shows that 47%(19/40) of the patients with
      HIV who developed AF had CD4 count lower than 250 as compared to 20%(8/40) in the
      control group (P value = 0.017) Conclusion: The data supports the presence of a
      relationship between HIV and AF. Patients with lower CD4 counts are more
      susceptible to develop AF.

PMID- 28496728
TI  - Risk of Arrhythmia Recurrence After Successful Ablation of Lone Atrial
      Fibrillation.

PMID- 28496729
TI  - Cardiac Resynchronization Therapy in Patients with Atrial Fibrillation - Worth
      the Effort?
AB  - Congestive heart failure (CHF) and atrial fibrillation (AF) are two increasingly
      common conditions that predispose to each other and frequently coexist. Cardiac
      resynchronization therapy(CRT) has emerged as an important therapeutic modality
      for selected patients with end-stage CHF. However, despite the high prevalence of
      AF in patients eligible for CRT, almost all the randomized clinical trials that
      validated the benefit of resynchronization therapy excluded patients with
      preexisting AF. In this review, we examine the available evidence on the benefits
      and limitations of CRT in patients with AF and discuss recent data that narrowed
      the knowledge gap on this topic.

PMID- 28496730
TI  - Demographic Characteristics and Patterns of Medication in Atrial Fibrillation
      Patients in South West Ontario: Insights from a Large Primary Care Database.
AB  - Background: Information about current practice in primary care-based management
      of atrial fibrillation (AF) can help to improve care quality. Purpose: To assess
      the epidemiology of AF and current patterns of treatment in order to identify
      therapeutic trends and aspects of current practice that may allow for care-gap
      identification. Methods: We scrutinized the anonymized records of the South
      Western Ontario database (SWO) collected between July 2002 and October 2008 for
      information about the characteristics and management of AF patients. Results:
      From a population of ~168,000 patients we identified 4922 patients with a
      diagnosis of AF (2.9%). The recorded prevalence of AF increased with age, from
      <2% at age <60 years to 6% in the age range 71-75 years and 10% at age >=81
      years. AF patients were characterized by an unfavourable cardiovascular risk
      profile including widespread hypertension (54% of all cases), coronary artery
      disease (37%) and heart failure (21%), many cases of which were advanced (New
      York Heart Association class III or IV). Diabetes (22%) and dyslipidaemia (31%)
      were also widely prevalent. The most frequently prescribed anti-arrhythmic drugs
      (AADs) were sotolol (n=798), amiodarone (n=712) and propafenone (n=451). Recorded
      use of flecainide was relatively low (n=175). Rate control-agents were being
      prescribed for 1838 patients, beta-blockers for 1311 patients and calcium channel
      blockers (CCBs) for 784 patients. Use of anticoagulants was higher among patients
      assigned to AADs than among those assigned to rate-control drugs (>25% vs. ~10%).
      Overall prescription rates for other concomitant medications were >50% for ACE
      inhibitors/ARBs, 30-35% for statins and beta-blockers, and 27-29% for diuretics,
      digoxin and CCBs. Conclusions: These Canadian patients with AF were relatively
      elderly and had multiple concomitant cardiovascular conditions and medications.

PMID- 28496731
TI  - Enhancing Cardiac Resynchronization Therapy for Patients with Atrial
      Fibrillation: The Role of AV Node Ablation.
AB  - Cardiac resynchronization therapy (CRT) has evolved as an effective therapy for
      patients with congestive heart failure (CHF) and ventricular dyssynchrony,
      currently defined as a wide QRS on the electrocardiogram. While multiple
      randomized controlled trials have confirmed the favorable effects of CRT on
      mortality and heart failure symptoms for patients in sinus rhythm, only recently
      observational studies have begun to suggest a similar benefit for patients with
      atrial fibrillation (AF) and dyssynchrony. Yet, implementing effective
      biventricular pacing in patients with AF can be problematic due to competing
      intrinsic AV conduction. For patients with depressed ejection fractions needing
      AV node (AVN) ablation to control fast ventricular rates, biventricular pacing
      has been shown to be superior to right ventricular pacing alone. When consistent
      pacing (over 90% of the time) cannot be achieved in AF patients due to a rapid
      ventricular response despite pharmacological therapy, AVN ablation should be
      considered. The additional benefit of performing AVN ablation to promote
      biventricular pacing in patients without rapid ventricular rates remains
      uncertain. A randomized controlled trial is needed to test the incremental
      benefit of AVN ablation to promote biventricular pacing in heart failure patients
      with AF and wide QRS.

PMID- 28496732
TI  - Atrial Fibrillation and Oral Anticoagulation in Chronic Kidney Disease.
AB  - Due to several unfavorable epidemiological changes, chronic kidney disease (CKD)
      and treatment of its associated cardiovascular morbidity have become a worldwide
      problem. Thus, atrial fibrillation (AF) is the most common arrhythmia and
      frequently associated with renal impairment: prevalence for AF is up to 27% in
      long-term hemodialysis patients and in general more than 25% in all CKD patients
      70 years and older. Thromboembolism and stroke are the major complications of AF.
      Two-year death rates for CKD patients after stroke range between 55% and 74%.
      Although treatment of AF in the general population is well defined, patients with
      CKD and AF are often undertreated due to lack of studies and guidelines. In this
      review recent data concerning incidence and prevalence of AF, stroke, and major
      bleedings in CKD patients are presented. Particular attention is paid to the
      available data about the different types of oral anticoagulation therapy with
      regard to CKD stage, including the new oral anticoagulant drugs dabigatran,
      rivaroxaban, and apixaban. Stratification algorithms for stroke risk in general,
      and individualized risk stratification for oral anticoagulation in CKD patients
      are discussed in detail.

PMID- 28496734
TI  - Epicardial Fat and Atrial Fibrillation: A Review.
AB  - Atrial fibrillation (AF) is a progressive disorder that increases with age.
      Obesity is an important risk factor for AF. Pericardial fat is an active adipose
      tissue in close proximity to the heart and has been shown to be a risk factor for
      structural as well as coronary artery disease independent of body mass index.
      Recent studies suggest a role of epicardial fat in atrial remodeling as well as
      AF burden. This review will summarize the recent evidence linking epicardial fat
      and AF.

PMID- 28496733
TI  - Risks from Catheter Ablation of Atrial Fibrillation: A Review of Methods,
      Efficacy, and Safety.
AB  - Atrial fibrillation (AF) is the most common arrhythmia and is a significant
      burden to healthcare cost. AF causes congestive heart failure, thromboembolic
      events such as stroke and intolerable symptoms in some patients. With the
      advances and increasing experience in catheter ablation, there is now an
      established role for catheter ablation in patients with atrial fibrillation. The
      risks, complications and patient features associated with it are increasingly
      recognized. A recent worldwide survey has shown an increasing number of medical
      centers that are practicing catheter ablation of atrial fibrillation,
      predominantly with pulmonary vein isolation techniques. However, catheter
      ablation is an invasive therapy in AF and is associated with a few major
      complications. Patient selection, ablation technique, and catheter energy source
      all influence the efficacy and safety of the procedure. Finally, while several
      randomized control trials have compared the efficacy of catheter ablation versus
      antiarrhythmic drug therapy, a number of trials are on the horizon to explore its
      role as a first line therapy for atrial fibrillation. New energy catheter energy
      sources are also being explored.

PMID- 28496735
TI  - Treating Atrial Fibrillation With Cryoballoon Technology.
AB  - Cryoballoon ablation has emerged as a novel tool to perform pulmonary vein
      isolation. The aim of this paper is to review the advantages, drawbacks as well
      as possible complications and clinical outcomes of this technology and to discuss
      some important technical issues.

PMID- 28496737
TI  - Temporal and Spatial Indices of AF Regularization Predict Intraprocedural AF
      Termination and Outcome.

PMID- 28496739
TI  - Anemia and Atrial Fibrillation.

PMID- 28496738
TI  - Impact of Chronic Anemia on the New-Onset Atrial Fibrillation in the Elderly: It
      May Not Be What We Have Thought.
AB  - Objective: To determine if a clinically significant relation exists between
      chronic anemia and the new-onset atrial fibrillation (AF) in the elderly
      population from a community setting. Patients and Methods: This is a single
      center community-based retrospective cohort study. Data were collected on 3867
      patients over the age of 65 years presenting to the Mercy Medical Center in the
      year 2006. Patients without AF were divided into anemic and non-anemic groups and
      were followed over the next two years for the new-onset AF. Chronic anemia was
      defined as hemoglobin level less than 13g/dl in males and less than 12g/dl in
      females from two laboratory values checked at least 4 months apart. Results: Of
      the 2873 patients without AF, 2382 (83%) patients were non-anemic. 491 patients
      were anemic. New-onset AF was found in 7.5 % of the anemic patients and 5.5% of
      the non-anemic patients. After the adjustment for comorbid conditions, chronic
      anemia is not associated with new-onset AF (p=0.922). Conclusion: In this study
      cohort of elderly community-based patients, chronic anemia is not associated with
      the new-onset AF.

PMID- 28496736
TI  - Altered Excitation-Contraction Coupling in Human Chronic Atrial Fibrillation.
AB  - This review focuses on the (mal)adaptive processes in atrial excitation
      contraction coupling occurring in patients with chronic atrial fibrillation.
      Cellular remodeling includes shortening of the atrial action potential duration
      and effective refractory period, depressed intracellular Ca2+ transient, and
      reduced myocyte contractility. Here we summarize the current knowledge of the
      ionic bases underlying these changes. Understanding the molecular mechanisms of
      excitation-contraction-coupling remodeling in the fibrillating human atria is
      important to identify new potential targets for AF therapy.

PMID- 28496740
TI  - Atrial Fibrillation at an Internal Medicine Ward: Clinical and Prognostic
      Implications.
AB  - Background: Little is known about atrial fibrillation (AF) appearing during
      hospitalization in an Internal Medicine ward. Purpose: We aimed to investigate
      characteristics and prognostic significance of in-hospital onset AF. Methods: We
      studied 249 consecutive unselected patients admitted to this medical department
      with paroxysmal or persistent AF (out-of-hospital group) or AF developed during
      hospitalization (in-hospital group). Demographic, clinical, laboratory,
      electrocardiographic and echocardiographic data and all-cause mortality following
      discharge were recorded and compared between the groups Results: Diabetes
      mellitus (p=0.05), renal dysfunction (p<0.001), chronic lung disease (p=0.03) and
      history of stroke (p=0.01) were found more common in the in-hospital group (56
      patients), compared to the out-of-hospital group (193 patients). Patients from
      the in-hospital group were more likely to have recurrent episodes of AF during
      hospitalization (p=0.002), were more frequently treated with amiodarone
      (p<0.001), discharged in sinus rhythm (p=0.04) and with medications for rhythm
      control (p=0.04). Time from onset to termination of AF (p<0.001) and hospital
      stay (p<0.001) were longer in the in-hospital group. On a median of 39-months
      follow-up, survival rate was lower in the in-hospital vs. out-of-hospital group
      (69.6% vs. 81.3%, p=0.025). Older age was significantly associated with shorter
      survival in the in-hospital group [odds ratio (OR)=1.87, 95% confidence interval
      (CI) 1.15-3.03, p=0.009]. In the out-of-hospital group, advanced age (OR=2.17,
      95%CI 1.51-3.10, p<0.001), no prior AF episode (OR=3.41, 95%CI 1.56-7.46,
      p=0.002), diabetes mellitus (OR=2.22, 95%CI 1.12-4.39, p=0.006) and renal
      dysfunction (OR=2.44, 95%CI 1.10-5.38, p=0.049) were significantly associated
      with shorter survival. Conclusion: Patients developing in-hospital AF differed
      from subjects hospitalized for AF with respect to the severity of the clinical
      profile and prognosis.

PMID- 28496741
TI  - Multi-Electrode Ablation Catheters for AF Ablation: Effective Reality or Elegant
      Experiment?

PMID- 28496742
TI  - Relationship Between Arrhythmia and Sleep Disordered Breathing.
AB  - The association between obstructive sleep apnea (OSA) and cardiovascular disease
      is well known. Data from most studies investigating the prevalence of OSA in
      atrial fibrillation (AF), and of AF in patients with OSA, have supported the
      relationship between these common diseases. In addition, several studies have
      shown a detrimental effect of OSA on AF treatment. These reports vary
      considerably in methodology, and are particularly diverse in their definitions
      and diagnosis of OSA and patient populations studied. Considering these studies
      individually while exploring their methodological variations and the range of
      results achieved can reinforce the necessity of establishing standards for
      performing this important research. Reviewing these studies should en courage
      practitioners to reflect on how the methodologies, patients, and outcomes are
      relevant to their practices.

PMID- 28496743
TI  - Association Between BMI and QoL Improvement in AF Patients Following Catheter
      Ablation.

PMID- 28496744
TI  - The Estimated Risk of Atrial Fibrillation Related to Alcohol Consumption.
AB  - The risk of acute heavy alcohol intake on the development of atrial fibrillation
      (AF), aka ?holiday heart syndrome?, has been well-described. However, whether
      chronic alcohol intake is also associated with increased risk of AF, or might
      even be protective as has been observed with other cardiac conditions, is more
      uncertain. A number of studies, from basic science to large cohort studies have
      been performed to analyze the association between alcohol and AF. Basic-level
      studies have found that alcohol causes changes in tissue electrophysiology, ion
      channels, and circulating hormones, which might promote development and
      maintenance of AF. Clinical studies have generally shown groups with the highest
      regular intake of alcohol to be at increased risk, with no association with more
      moderate use. However, these studies have not always accounted for other AF risk
      factors, been inconsistent in the assessment and validation of the quantity of
      alcohol consumed across populations, and been unable to completely separate
      drinking patterns from overall health of participants. As a result, solid
      conclusions about a threshold level for ?safe? chronic alcohol intake cannot be
      made with regard to AF risk, but it appears to be safe within currently
      recommended limits of 1 drink daily for women and 2 for men. In this review, we
      discuss these findings, limitations, and conclusions.

PMID- 28496745
TI  - The Relationship Between Atrial Fibrillation and Chronic Kidney Disease :
      Epidemiologic and Pathophysiologic Considerations for a Dual Epidemic.
AB  - : Atrial fibrillation (AF) presently affects over 2 million Americans, and the
      magnitude and population burden from AF continues to increase concomitant with
      the aging of the U.S. POPULATION: Chronic kidney disease (CKD) is present in 13%
      of individuals in the U.S., and the prevalence of CKD is also rapidly increasing.
      The increasing population burden of CKD and AF will profoundly affect the
      clinical and public health, since CKD and AF are both associated with lower
      quality of life, increased hospitalization rates, and a greater risk of heart
      failure, stroke, and total mortality. AF and CKD often co-exist, each condition
      predisposes to the other, and the co-occurrence of these disorders worsens
      prognosis relative to either disease alone. The shared epidemiology of CKD and AF
      may be explained by the strong pathophysiologic connections between these
      diseases. In order to promote a better understanding of CKD and AF, we have
      reviewed their shared epidemiology and pathophysiology and described the natural
      history of patients affected by both diseases.

PMID- 28496746
TI  - Chronic Kidney Disease and Atrial Fibrillation: A Contemporary Overview.
AB  - Chronic kidney disease (CKD) is associated with substantial cardiovascular
      morbidity, including myocardial infarction, heart failure and stroke. Similar to
      CKD, atrial fibrillation (AF) is a prevalent arrhythmia that increases risk for
      both stroke and overall mortality. Recent studies demonstrate that both
      prevalence and incidence of AF is higher in patient with versus without renal
      impairment and risk for developing AF increases as renal function worsens.
      Potential mechanisms for the higher burden of AF in CKD patients include but are
      not limited to augmented sympathetic tone, activation of the renin-angiotensin
      aldosterone system and myocardial remodeling. Similar to the general population,
      AF confers an increased risk for both stroke and overall mortality in the CKD
      population. The safety and efficacy of antithrombotic therapy across the spectrum
      of CKD remains unknown, however, as patients with advanced renal failure are
      frequently excluded from randomized trials. While treatment with vitamin K
      antagonists appears to reduce ischemic complications without significant bleeding
      harm in patients with mild to moderate CKD and AF, the risk benefit ratio of
      anticoagulation among thosewith advanced renal failure on dialysis requires
      further investigation. Prospective, randomized trials are war ranted to define
      the impact of antithrombotic therapy on reducing stroke risk in patients with
      both AF and CKD.

PMID- 28496747
TI  - Atrial Fibrillation Associated with Heart Failure, Stroke and Mortality.
AB  - Atrial Fibrillation (AF) is the most common arrhythmia in the western world.
      Because AF prevalence rises with age and western populations are increasingly
      aging, AF has been called a "growing epidemic", especially among older persons,
      with social and economic consequences. AF may concur to disability and may
      cluster with other co-existing clinical conditions. AF is an independent risk
      factor for stroke by increasing the thromboembolic risk profile and is associated
      with heart failure severity. Among persons with AF, prevalence of stroke,
      coronary heart disease, peripheral artery disease, cognitive impairment and
      physical disability is significantly higher. AF is associated with higher risk of
      mortality through the association with stroke and heart failure: ischemic strokes
      are more severe if AF is present and AF may represent a marker of more severe
      heart failure. Independently of other known predictors of mortality, death rates
      are almost doubled by AF. AF, therefore, is a considerable source of morbidity
      and mortality, is associated with disability, and is a major determinant of
      quality of life.

PMID- 28496748
TI  - Cost-Effective Medicines for Stroke Prophylaxis in Patients with Atrial
      Fibrillation.
AB  - Non-valvular atrial fibrillation is the most common arrhythmia encountered in
      clinical practice and is associated with substantial healthcare costs. The risk
      of thromboembolic stroke is 3-5 times higher in patients with atrial fibrillation
      compared with the general population. Until the recent emergence of direct
      thrombin (factor IIa) and factor Xa inhibitors, antithrombotic therapy for atrial
      fibrillation was achieved with antiplatelet agents or vitamin K antagonists,
      which are considered cost-effective strategies when compared to no treatment. Now
      newer agents, such as the direct thrombin inhibitor dabigatran, can lower
      thromboembolic events and reduce the risk of fatal and intracerebral hemorrhage
      compared with warfarin, in addition to eliminating the need for costly
      therapeutic monitoring. Multiple analyses have shown that dabigatran, when
      compared with warfarin therapy that achieves a time in therapeutic range (TTR)
      consistent with previous large-scale trials, is a cost-effective approach to
      antithrombotic therapy in atrial fibrillation, ranging from $16,385 to $86,000
      per quality-adjust life-year (QALY) gained. It has been shown to be especially
      cost-effective (QALY < $50,000) for high stroke-risk patients, those with a
      CHADS2 score of > 3 (barring excellent INR control) and for lower-risk patients
      with a CHADS2 of 2 but concomitant high risk of hemorrhage. In addition, factor
      Xa inhibitors, such as rivaroxaban (recently approved by the Federal Drug
      Administration [FDA]) and apixaban, may exhibit the same cost savings as
      dabigatran in terms of reduction of bleeding and elimination of therapeutic level
      monitoring costs. Going forward, the use of these agents and their role in
      thromboembolic stroke prophylaxis will need to be evaluated on a patient-by
      patient basis, balancing consideration of the patient?s stroke and bleeding
      risks, as well as quality of life post-therapy.

PMID- 28496749
TI  - Transient ST Elevation in Vagally Mediated Atrial Fibrillation.
AB  - We report a case of vagally mediated atrial fibrillation on a young otherwise
      healthy man, with straight type ST-segment elevation in inferolateral leads that
      resolved a few hours after restoration of sinus rythm, a phenomenon that has
      never been previously reported. Even though no definite conclusion about the
      underlying mechanism of the ST-elevation can be made, this effect might probably
      be the result of intense parasympathetic tone and could be used to differentiate
      the causality.

PMID- 28496750
TI  - Atrial Fibrillation in Acute Coronary Syndrome.
AB  - Atrial fibrillation (AF) is a common cardiac arrhythmia occurring in an estimated
      2.7 to 6.1 million people in the United States. The risk factors for the
      development of AF are very similar to those for developing coronary artery
      disease, and AF is often associated with acute coronary syndrome (ACS) and acute
      myocardial infarction (MI). Overall, AF complicates approximately 10% of acute
      infarcts and the incidence rate is comparable between the thrombolytic and
      percutaneous coronary intervention (PCI) eras. Prior to widespread use of
      thrombolysis, the incidence of AF during acute MI was as high as 18%. Moreover,
      AF is a marker for increased long term mortality post infarct. Over the past 20
      years, the relative mortality risk for patients with AF post MI has remained
      around 2.5 times that for patients without AF. The treatment of AF in the setting
      of MI and ACS is similar to without; however there is often an increased urgency
      to limiting rapid heart rates which may exacerbate acute ischemia. Cardioversion
      and IV amiodarone may be utilized more liberally in this setting than otherwise.
      Anticoagulation is usually required both for the treatment of MI and possible
      PCI, as well as for cerebral vascular accident prevention from AF-induced
      thromboembolism. Often patients require triple-therapy for optimal treatment of
      both conditions, and special considerations for bleeding risk must be analyzed.

PMID- 28496752
TI  - Atrial Fibrillation, Alcohol, Obesity and more....

PMID- 28496751
TI  - Stroke and Death Prediction with the Impact of Vascular Disease in Patients with
      Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia encountered in the U.S.
      and the growing burden of AF has profound health implications due to the
      association of AF with an increased risk of stroke, heart failure, and mortality.
      AF is a significant risk factor for thromboembolic stroke; and also independently
      increases total mortality in patients with and without cardiovascular disease.
      Various risk stratification schemes such as CHADS2 and CHA2DS2-VASc have been
      implemented in clinical practice to determine the risk of cardio-embolic stroke,
      and need for thrombo-prophylaxis in patients with AF. AF is also closely related
      to the pathophysiology of other cardiovascular and peripheral vascular disease.
      Many patients with AF have associated atherosclerosis given that many risk
      factors for atherosclerosis also predispose to AF. Myocardial infarction (MI) is
      also closely related to AF and its clinical course is affected by new onset AF.
      This review elucidates the impact of AF on major adverse cardiovascular events
      and mortality outcomes in relation to stroke, coronary artery disease and
      peripheral vascular disease.

PMID- 28496753
TI  - Microwave Ablation in Mitral Valve Surgery for Atrial Fibrillation (MAMA).
AB  - Objective: Microwave ablation in conjunction with open heart surgery is effective
      in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF). In
      patients assigned for isolated mitral valve surgery no prospective randomized
      trial has reported its efficacy. Methods: 70 patients with longlasting AF where
      included from 5 different centres. They were randomly assigned to mitral valve
      surgery and atrial microwave ablation or mitral valve surgery alone. Results: Out
      of 70 randomized, 66 and 64 patients were available for evaluation at 6 and 12
      months. At 12 months SR was restored and preserved in 71.0 % in the ablation
      group vs 36.4 % in the control group (P=0.006), corresponding figures at 6 months
      was 62.5 % vs 26.5 % (P=0.003). The 30-day mortality rate was 1.4 %, with one
      death in the ablation group vs zero deaths in the control group. At 12 months the
      mortality rate was 7,1 % (Ablation n=3 vs Control n=2). No significant
      differences existed between the groups with regard to the overall rate of serious
      adverse events (SAE) during the perioperative period or at the end of the study.
      16 % of patients randomized to ablation were on antiarrhytmic drugs compared to 6
      % in the control group after 1 year (p=0.22). Conclusion: Microwave ablation of
      left and right atrium in conjunction with mitral valve surgery is safe and
      effectively restores sinus rhythm in patients with longlasting AF as compared to
      mitral valve surgery alone.

PMID- 28496754
TI  - Statin and Atrial Fibrilation: When does it work?
AB  - In the recent years, some clinical and experimental studies have suggested that
      the use of statins may protect against atrial fibrillation (AF). A relation
      between inflammation and the development of AF has been described, and the potent
      anti-inflammatory and antioxidant properties of statins may make them effective
      in preventing the development of AF. A global analysis of the literature suggests
      that the use of statins is associated with a decreased risk of incidence or
      recurrence of AF in some cases. However, this beneficial effect is not seen for
      all types of AF in all the patients. The use of statins seems associated 1) with
      a lack of benefit in primary prevention of AF, 2) with a significant but
      heterogeneous decreased risk of recurrence of AF in secondary prevention, and 3)
      with a very significant and homogeneous reduction for the risk of post operative
      AF. An intensive lipid lowering statin regimen does not provide greater
      protection against AF. Patients with coronary heart disease are curr ently
      treated with statins in most cases, and this may not have an impact on their
      treatment. In contrast, it remains to determine more accurately if statins may
      bring a significant benefit for some AF patients without any type of established
      atherosclerotic disease or with a low risk of atherogenesis. Since it remains
      uncertain whether the suppression of AF in these patients is beyond doubt
      beneficial, prescribing statins for this purpose alone should not be recommended
      at the present time.

PMID- 28496755
TI  - Apixaban in patients with Atrial Fibrillation: A Systematic Review.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia which increases
      the risk of stroke and systemic embolism by 5- fold, it is a major global public
      health problem. Stroke is associated with greatest mortality and morbidity in
      patients with AF. Strokes associated with AF are especially large and disabling,
      and consequently primary prevention is paramount. Antithrombotic therapy is the
      mainstay of stroke prevention. Vitamin K antagonists (VKA's) have been the
      standard anticoagulants in stroke prophylaxis for patients with AF for decades.
      Despite their effectiveness, they are limited by several factors such as narrow
      therapeutic index, drug- drug interactions, slow onset and offset of action,
      hemorrhage and routine anticoagulation monitoring to maintain therapeutic
      international normalized ratio (INR). During recent times, various novel
      anticoagulants have been developed to expand the therapeutic option for stroke
      prevention. Apixaban is a novel oral anticoagulant which has been developed and
      clinically investigated for prevention of stroke in AF patients. This review
      discusses the pharmacological properties, results of clinical trials
      investigating role of apixaban for prevention of stroke and its future potential
      in clinical practice.

PMID- 28496756
TI  - Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with
      Atrial Fibrillation.
AB  - : Atrial fibrillation (AF) is the most common sustained atrial arrhythmia
      conferring a higher morbidity and mortality. Despite the increasing incidence of
      AF; available therapies are far from perfect. Dietary fish oils, containing omega
      3 fatty acids, also called polyunsaturated fatty acid [PUFA] have demonstrated
      beneficial electrophysiological, autonomic and anti-inflammatory effects on both
      atrial and ventricular tissue. Multiple clinical trials, focusing on various
      subsets of patients with AF, have studied the role of PUFA and their potential
      role in reducing the incidence of this common arrhythmia. While PUFA appears to
      have a beneficial effect in the primary prevention of AF in the elderly with
      structural heart disease, this benefit has not been universally observed. In the
      secondary prevention of AF, PUFA seems to have a greater impact in the reducing
      AF in patients with paroxysmal or persistent AF, stages of AF associated with
      less atrial fibrosis and negative structural remodeling. However, AF suppression
      has not been consistently demonstrated in clinical trials. In patients undergoing
      heart surgery, increasing PUFA intake has yielded mixed results in terms of AF
      prevention post-operatively; however, increased PUFA has been associated with a
      reduction in hospital stay. Therefore recommending the use of PUFA for the
      purpose of AF reduction remains controversial. This is in part attributable to
      the complexity of AF. Other conflicting variables include: heterogeneous patient
      populations studied; variable dosing; duration of follow-up; comorbidities; and,
      concomitant pharmacotherapy. This review article reviews in detail available
      basic and clinical research studies of fish oil in the treatment of AF, and its
      role in the treatment of this common disorder. ABBREVIATIONS: AF=Atrial
      fibrillation, CHS=Cardiovascular Health Study,CABG=Coronary artery bypass
      surgery, d=Day, DHA=Docosahexaenoic acid, EPA=Eicosapentaenoic acid, ERP=
      Effective refractory period, g=Gram, PAF= Paroxysmal atrial fibrillation, PeAF=
      Persistent atrial fibrillation PUFA= Polyunsaturated fatty acid.

PMID- 28496758
TI  - Remote Magnetic Navigation System Guided Radiofrequency Ablation of Intra Atrial
      Reentrant Tachycardia in Corrected Transposition of Great Arteries.
AB  - Atrial arrhythmias are delayed manifestations after atrial switch procedures for
      d-transposition of the great arteries. Often times, these arrhythmias are
      intraatrial reentry tachycardias that arise in the pulmonary venous neo-atrium.
      Access and ablation in the pulmonary venous neo-atrium may require baffle
      puncture, risking damage to the baffle. We describe a case of neoatrial
      arrhythmia ablation in d-transposition of the great arteries using remote
      magnetic guided catheter navigation system using a retrograde approach without
      doing a baffle puncture.

PMID- 28496757
TI  - The Role of Atrial Structural Remodeling in Atrial Fibrillation Ablation:An
      Imaging Point of View for Predicting Recurrence.
AB  - Atrial fibrillation (AF) is the most common arrhythmia and is associated with a
      significant morbidity and mortality. Invasive catheter ablation of AF has emerged
      as an effective therapy for patients with symptomatic AF. Atrial remodeling,
      particularly structural remodeling, is important not only for AF persistence but
      also for AF recurrence after ablation. Atrial dilation and fibrosis are two of
      the core processes involved in atrial structural remodeling. Increased
      automaticity and triggered activity occur in atrial structural remodeling, which
      may cause difficulty in maintaining sinus rhythm after ablation. Furthermore, an
      enlarged left atrium (LA) may increase the difficulty in achieving catheter
      stability and thereby require more energy to complete AF ablation. AF causes
      similar remodeling in both the left and right atria (RA), and myocardial changes
      in both atria influence AF recurrence. A non-invasive assessment of fibrotic
      structural remodeling helps predict the outcome of AF ablation. A varie ty of
      cardiac imaging modalities, such as two- or three-dimensional echocardiography or
      multi-detector row computed tomography, have been used to estimate the magnitude
      of atrial structural remodeling by measuring atrial volume or LA function.
      Furthermore, delayed enhanced cardiac magnetic resonance imaging has been used to
      detect not only atrial fibrosis but also the effect of the ablation point. Thus,
      atrial remodeling, particularly structural remodeling, plays an important role in
      AF recurrence. These non-invasive imaging modalities are significant tools for
      estimating atrial enlargement to improve patient selection for AF ablation at the
      point of paroxysmal AF, and for estimating atrial fibrosis to select the AF
      treatment including ablation strategy at the point of development to persistent
      or permanent AF.

PMID- 28496759
TI  - Role of Cardiac Imaging (CT/MR) Before and After RF Catheter Ablation in Patients
      with Atrial Fibrillation.
AB  - Pre-procedure X-ray computed tomography (CT) and magnetic resonance imaging (MRI)
      angiography are commonly used to delineate the complex and variable relationship
      of the left atrium, pulmonary veins, and surrounding structures. 3D CT and MR
      angiography are routinely incorporated into electroanatomic mapping systems to
      guide ablation lesion placement in the context of patient specific anatomy. Post
      procedure CT and MRI have also proven useful for evaluating complications such as
      pulmonary vein stenosis. In the future, these imaging modalities may be used to
      visualize more detailed tissue characteristics such as atrial fibrosis and
      ablation lesions. This could improve selection of patients for different
      treatment strategies and perhaps guide more effective ablation. This review will
      discuss current and emerging applications of CT and MRI before and after
      radiofrequency catheter ablation of atrial fibrillation.

PMID- 28496760
TI  - Post Ablation Left Atrial Tachycardia: Understanding Mechanism, Prevention and
      Treatment.
AB  - Currently, post-ablation Atrial Tachycardias (ATs) represent a growing clinical
      problem particularly in patients with persistent AF undergoing a more extensive
      substrate ablation. Understanding mechanisms and location of potentially widely
      located arrhythmogenic substrates in the left atrium is crucial for successful
      ablation. Mapping and ablation are challenging since complex and multiple ATs may
      frequently develop during the index procedure and before conversion to sinus
      rhythm. Use of irrigated ablation guided by detailed 3-D electroanatomic
      activation maps combined with entrainment pacing is effective with excellent
      acute and long-term success rates, rarely requiring multiple procedures.

PMID- 28496761
TI  - Should Atrial Fibrillation Burden Be A Feature to Guide Thromboembolism
      Prophylaxis?
AB  - : Atrial fibrillation (AF) is a well-known risk factor for cerebrovascular events
      and systemic emboli. However, the frequency and duration of AF necessary to be
      considered at risk for thrombus formation is unknown. This review summarizes the
      literature regarding AF burden and risk for thromboembolism. Previously, no
      distinction was made between patients who had paroxysmal versus persistent AF in
      regards to initiation of anticoagulation. Recently though, given an enhanced
      ability to detect even very brief paroxysms of AF via stored device diagnostics,
      the issue has been readdressed. However, despite multiple studies no clear
      threshold for AF burden to mandate anticoagulation has been established. In
      addition, there is a growing body of evidence which suggests that the
      pathophysiology of thrombus formation in AF involves mechanisms beyond just
      stasis due to protracted episodes of discoordinate atrial contraction. Therefore,
      once AF has been diagnosed and the risk-benefit ratio favors anticoagulation,
      therapy should be initiated and continued indefinitely unless a bleeding
      contraindication develops. ABBREVIATIONS: AF = atrial fibrillation, AT = atrial
      tachycardia, LAA = left atrial appendage, PAF = paroxysmal atrial fibrillation,
      SE = systemic emboli.

PMID- 28496762
TI  - The Use of Ranolazine in the Management of Recurrent Atrial Fibrillation After
      Percutaneous Radiofrequency Ablation.
AB  - Long-term medical treatment options for atrial fibrillation (AF) include rate
      control as well as rhythm-control therapy with various antiarrhythmics. However,
      because of the limited efficacy and potential side effects of these medications,
      percutaneous and surgical ablations in AF patients have evolved as alternative or
      additional approaches to achieve rhythm-control. Nonetheless, arrhythmia
      recurrences may also occur after these procedures. Thus, the search for
      complementary treatment options continues.Ranolazine possesses antiarrhythmic
      effects in atrial myocytes via blockade of sodium channels. These properties
      facilitate AF suppression in animal models and human subjects. We report a
      patient with persistent AF that was refractory to medical management and
      percutaneous catheter ablation. She has remained in sinus rhythm for at least 18
      months after the initiation of ranolazine.

PMID- 28496765
TI  - The Kansas City Heart Rhythm Symposium.

PMID- 28496763
TI  - Primary Prevention of Atrial Fibrillation where are we in 2012?
AB  - Drugs to alter or delay myocardial remodelling associated with heart failure,
      hypertension, or inflammation in the post-operative setting, may prevent the
      development of atrial fibrillation. Current experimental and clinical evidences
      support specific treatments for defined patient population (i.e. ACE-inhibitors
      and ARB for chronic heart failure and hypertension expecially with LV
      hypertrophy; statins, corticosteroids and possibly colchicine after cardiac
      surgery).

PMID- 28496764
TI  - Echocardiography In the Prediction of Atrial Fibrillation Recurrence: A Review.
AB  - Atrial fibrillation (AF) is a very common sustained arrhythmia. Co-morbidities
      and age signifi cantly accelerate the progression of AF to persistent and
      permanent forms and the development of complications. The rate of AF recurrence
      is 10% in the first year after the initial diagnosis (25-50% in the first month
      after restoration of sinus rhythm) and about 5% per annum thereafter. Left
      ventricular (LV) diastolic dysfunction degree has been associated with new-onset
      AF and in the last few years many new parameters to evaluate diastolic function
      were introduced and validated, even in patients with AF. Aim of this review was
      to summarize echocardiographic parameters, focusing on new tools, to evaluate
      patients with AF and to explore the role of echocardiographic evaluation to
      predict recurrence of the arrhythmia.

PMID- 28496766
TI  - Impact of Atrial Fibrillation on Coronary Blood Flow: A Systematic Review.
AB  - Patients with atrial fibrillation (AF) frequently present with symptoms
      suggestive of myocardial isch- aemia, even in the absence of significant CAD,
      that seem to be attributable to abnormalities of myocardial perfusion and
      perfusion reserve. According to the results of recent human and previous
      experimen- tal studies the increase in coronary artery blood flow during AF is
      smaller, while the coronary vascular resistance during the arrhythmia does not
      decrease as much as we would expect, suggesting a mismatch between coronary blood
      flow and myocardial metabolic demand. AF itself diminishes coronary flow reserve,
      especially in the subendocardial layer, partly as a result of the increase in the
      myocardial com- ponent of coronary vascular resistance, and it is possible that
      irregular ventricular rhythm may play an important role. The mismatch of coronary
      blood flow and myocardial metabolic demand, especially in view of the severe
      reduction in coronary flow reserve, may have deleterious consequences that are
      not limited to patients with CAD.

PMID- 28496767
TI  - Atrial Fibrillation and the Role of LAA in Pathophysiology and Clinical Outcomes?
AB  - Left atrial appendage (LAA) is a source of thromboembolism especially in patients
      with non valvular atrial fibrillation (AF). It is reasonable to accept LAA as a
      distinct part of left atrium (LA) with unique anatomical and physiological
      properties. Advances in imaging modalities increased the knowledge about
      anatomical and physiological characteristics of LAA. It is important to prevent
      the AF patients from systemic thromboembolic events, and new pharmacological and
      non pharmacological management approaches demonstrate encouraging results. Also
      pulmonary vein isolation which has been accepted as a curative and useful
      treatment option for the treatment of drug resistant AF has been helpful in
      understanding the electrophysiological properties of LAA. Accumulating data
      revealed that LAA continues to be the one of the most important structure of
      heart during AF because of its distinctive anatomical, mechanical, and
      electrophysiological properties.

PMID- 28496768
TI  - Mortality Risk Associated with AF in Myocardial Infarction Patients.
AB  - Atrial fibrillation (AF) complicating myocardial infarction (MI) has been a
      controversial topic for the last few decades. It has generated a plethora of
      debates regarding whether it is a risk indicator of co-morbidities and poor
      haemodynamic status or independent causal mediator of poor outcomes. The
      management of this condition has also been idiosyncratic probably due to
      confusion regarding its prognostic significance. We shall review the literature
      and attempt to elucidate the prognostic significance as well as evidence
      available for defining management strategies.

PMID- 28496770
TI  - Sustained Fibrillation Within the Left Atrial Appendage During Catheter Ablation
      for Recurrent Atrial Tachyarrhythmia.
AB  - The left atrial appendage (LAA) has recently been recognized as a potential
      source of arrhythmia in patients undergoing repeat ablation procedures for atrial
      fibrillation (AF). In this case report we describe sustained fibrillation
      contained entirely within the LAA, that continued even after electrical isolation
      of the LAA was performed. This case supports the concept that in selected
      patients with AF, catheter ablation strategies may need to incorporate LAA
      isolation to minimize recurrence.

PMID- 28496769
TI  - Predictors of Recurrence After Radiofrequency Ablation of Persistent Atrial
      Fibrillation.
AB  - Radiofrequency catheter ablation that targets the pulmonary veins is well
      established as a mainstay for drug-refractory, paroxysmal atrial fibrillation
      (AF). However, in patients with persistent AF, the ideal approach remains
      elusive. Further, despite the various additional ablation strategies that have
      been investigated in patients with persistent AF, the rate of recurrent atrial
      tachyarrhythmias after ablation remains relatively high. In this review, the
      predictors of recurrent atrial tachyarrhythmias after catheter ablation of
      persistent AF will be discussed.

PMID- 28496771
TI  - Should Physicians Continue to Recommend Fish Oil for Patients with Atrial
      Fibrillation?
AB  - Many physicians recommend the use of fish oil or omega-3 polyunsaturated fatty
      acids (n-3 PUFA) in atrial fibrillation (AF) patients. N-3 PUFA have demonstrated
      anti-fibrillatory properties in several animal studies, however, data regarding
      their efficacy in preventing AF in humans have been mixed. This article
      critically reviews studies that have investigated the use of n-3 PUFA for the
      secondary prevention of paroxysmal and persistent AF and the primary prevention
      of post-operative AF. We conclude that n-3 PUFA should no longer be recommended
      for use in any of these AF subtypes until more data are available.

PMID- 28496772
TI  - The Impact of Atrial Fibrillation Ablation on Quality of Life.
AB  - Quality of life (QoL) is a very important endpoint in trials reporting the
      efficacy of catheter ablation in patients with atrial fibrillation (AF). It has
      been shown that AF ablation significantly improves the QoL, but recent studies
      question the usefulness of the most used generic QoL instrument in AF patients.
      The complexity of the disease makes it mandatory to employ disease specific
      instruments in the assessment of QoL. This paper reviews the current knowledge of
      various QoL instruments, including the limitations and pitfalls, and the impact
      of AF ablation on the QoL.

PMID- 28496774
TI  - Abnormal Left Ventricular Filling and Postoperative Atrial Fibrillation After
      Cardiac Surgery.
AB  - Objective: Diastolic dysfunction has been associated with the development of
      atrial fibrillation (AF) in the community and recently in the postoperative
      setting. We hypothesized that abnormal left ventricular filling predicts AF after
      cardiac surgery, a common marker of poor outcomes. Methods: Cohort study of 233
      consecutive patients, who underwent coronary artery bypass grafting (CABG) and/or
      valve surgery. Early and late mitral inflow velocity (E, A) and deceleration time
      (DT) and early mitral annular velocity (e?) were obtained from echo within 6
      months prior to cardiac surgery. Associations with postoperative AF were studied
      with multivariable logistic regression. Results: Postoperative AF occurred in 65
      (28%) of patients, who were on average older, more likely to have had prior
      episodes of AF, had larger inferior vena cava diameter and shorter DT (189 +/-
      62ms vs. 214 +/- 63ms, p=0.007). Multivariable adjusted analyses demonstrated
      only DT (odds ratio [OR] 0.65 (95% confidence interval [CI] 0.40-0.97), older age
      (OR 2.62 (95% CI 1.68 - 4.10) and prior episodes of atrial fibrillation (OR 7.20,
      CI 1.41-36.8) to be independent predictors of postoperative AF. Patients with a
      DT <= 200ms (n=117) had a significantly longer length of hospital stay compared
      with those who had DT > 200ms (n=116) (median 7 days (interquartile range [IQR] 5
      10) vs. 6 days (IQR 5-7, p=0.0002). Conclusion: In patients who undergo cardiac
      surgery, a shorter DT of early mitral inflow identified greater risk for
      postoperative AF and a longer hospital stay. These results provide useful
      information for preoperative risk assessment and mechanistic understanding of
      postoperative AF.

PMID- 28496773
TI  - Atrial Fibrillation Complicating Acute Coronary Syndromes.
AB  - Atrial fibrillation frequently complicates myocardial infarction. Patients with
      atrial fibrillation complicating acute coronary syndrome have increased morbidity
      and mortality relative to patients that remain in normal sinus rhythm. No studies
      have identified a mortality benefit to rhythm control compared with rate control
      in the setting of acute coronary syndrome. Stroke prevention should be pursued
      with oral anticoagulation therapy, although the majority of patients with atrial
      fibrillation associated with acute coronary syndrome receive only antiplatelet
      therapy. There are several novel oral anticoagulant therapies now available, but
      these agents have not been well studied in combination with dual antiplatelet
      therapy. Therefore, warfarin as part of triple therapy is the most conservative
      approach until additional data becomes available.

PMID- 28496775
TI  - Atrial Fibrillation and Metabolic Syndrome: Understanding the Connection.
AB  - Metabolic syndrome, a constellation of conditions including obesity,
      dyslipidemia, hypertension and insulin resistance, has increased to epidemic
      proportions. Metabolic syndrome has been recognized as a risk factor for
      cardiovascular morbidity and is likely related to the epidemic of cardiovascular
      diseases. Perhaps not coincidentally, its growth in incidence has paralleled that
      of atrial fibrillation. Various components of metabolic syndrome have been known
      to have a role in the pathogenesis of atrial fibrillation. With the
      conglomeration of components seen in the metabolic syndrome, the risk for atrial
      fibrillation increases greatly. Several studies have elucidated the role of
      metabolic syndrome in the development of atrial fibrillation. Its role on the
      atrial substrate makes it an important determinant of progression of disease and
      failure of therapeutic strategies such as catheter ablation. Control of the
      various components of metabolic syndrome may ultimately lead to better outcomes
      in atrial fibrillation patients.

PMID- 28496776
TI  - AF and Venous Thromboembolism - Pathophysiology, Risk Assessment and CHADS-VASc
      score.
AB  - Atrial fibrillation (AF) and venous thromboembolism (VTE) are the two most common
      medical conditions managed with anti-coagulation therapy. Not all the patients
      with decreased mobility or AF have a similar risk for thromboembolism. The risk
      factors for venous thromboembolism and thromboembolism associated with AF are
      described in various studies. Considering that the two conditions have similar
      pathophysiologic basis of clot formation, one could imply that the risk factors
      for the occurrence of thrombosis could be similar. The present review focuses on
      the similarities and differences in the clinical risk factors of VTE and AF
      related thromboembolism. We will also be discussing the role of CHADS2-VASc
      scoring system in the risk assessment of VTE.

PMID- 28496777
TI  - Postoperative Atrial Fibrillation: Year 2011 Review of Predictive and
      Preventative Factors of Atrial Fibrillation Post Cardiac Surgery.
AB  - Background: Post cardiac surgery atrial fibrillation is common after cardiac
      surgery. Despite the advances in medical and surgical treatment, its incidence
      remains high and unchanged for decades. The aim of this review was to summarize
      studies published in 2011 on identifying factors, prevention strategies,
      treatment and effect of post operative atrial fibrillation (POAF) on the outcome
      after cardiac surgery. Methods: A review was performed on Medline, Embase and
      Chocrane on all of the English-language, peer-reviewed published clinical studies
      on POAF; studies investigating the mechanism of developing POAF, prevention,
      treatment and outcome were all included and analyzed. Case reports, studies on
      persistent/preoperative atrial fibrillation (AF), POAF after cardiac transplant,
      congenital cases and nonclinical studies were all excluded. We have also valuated
      these studies based on the type of the study, their originality, impact factor of
      the journal and their limitations. Results: Overall 62 studies were reviewed and
      analyzed; 26 on POAF predictive factors, 31 on preventative strategies and 6 on
      the outcome of POAF. Of these studies only two were original and the remaining
      were either performed in AF in general population (n=10) or had been studied and
      reported several times before in cardiac surgery (n=50). The average impact
      factor of the journals that POAF was published in was only 2.8 ranging between
      0.5 and 14.5. Conclusion: Post cardiac surgery atrial fibrillation is a multi
      factorial and complex condition. Cardiac surgery may be a risk factor for
      developing POAF in patients already susceptible to this condition and may not be
      a complication of cardiac surgery. Future studies should mainly focus on
      histological changes in the conductive tissue of atrium and related treatment
      strategies rather than predictive factors of POAF and more funding should be made
      available to study this condition from new and entirely different perspectives.

PMID- 28496778
TI  - Solutions to Reduce Cardiovascular Events in Patients with Atrial Fibrillation.
AB  - AF is the most common sustained cardiac rhythm disorder and an established risk
      factor for ischemic stroke. Ischemic strokes which occur in patients with AF are
      particularly severe and disabling. In addition, stroke recurrence is more common
      in patients with AF compared with those without it. Previous cerebrovascular
      events, age, hypertension, diabetes, and heart failure are risk factors for
      stroke in patients with AF. Various risk stratification schemes have been
      developed to quantify the risk for stroke in patients with AF. Currently, the
      most frequently used schemes to assess stroke risk in patients with AF are
      CHADS2, the ACC/AHA/ESC and American College of Chest Physicians (ACCP) schemes.
      Current risk scores are largely derived from risk factors identified from
      clinical trials and many potential risk factors have not been properly
      considered. Consequently, the stroke risk in many patients could be
      underestimated, and these patients could receive a suboptimal antithrombotic
      prophylaxis. There is substantial evidence for the benefit of vitamin K
      antagonists (VKA) in preventing stroke and reducing mortality. Novel oral
      anticoagulants are available for stroke prevention in patients with AF which
      overcome some of the difficulties associated with VKA. The introduction of novel
      oral anticoagulants in clinical practice and the advances in identifying patients
      at risk of stroke together may overcome many of the difficulties in providing
      effective stroke prevention for patients with AF.

PMID- 28496779
TI  - Combined Catheter Ablation for Atrial Fibrillation and Watchman(r) Left Atrial
      Appendage Occlusion Procedures: A Single Centre Experience.
AB  - Background Patients with atrial fibrillation (AF) may be interested in undergoing
      concomitant interventions of left atrial catheter ablation and device occlusion
      of the left atrial appendage (LAA). We report on the feasibility and outcome of
      combined procedures in a single centre case series. Methods Twenty-six patients
      underwent either first time or redo pulmonary vein isolation (PVI) procedures
      followed by successful implant of a Watchman(r) device. Results All procedures
      were uncomplicated with a mean case time of 233 +/- 38 minutes. Maximal LAA
      orifice dimension was smaller in 3 of 26 patients post PVI (range 1mm) than on
      the pre-procedural transoesophageal echocardiogram (TOE). A new peri-device leak
      of maximum 3mm was noted in 5 of 26 patients at 6 week follow-up TOE, but
      resolved in 4 by the 6 month follow-up. Conclusion Combined procedures for
      catheter ablation for AF and Watchman(r) LAA implant appear to be feasible and
      safe with satisfactory occlusion of the LAA maintained at follow-up.

PMID- 28496780
TI  - Typical Atrial Flutter - When Do You Say You Have Got It.

PMID- 28496782
TI  - Atrial Flutter Ablation Using MediGuideTM Non-fluoroscopic Catheter Tracking
      System: A Novel Technology to Reduce Radiation Exposure.
AB  - We describe the first case of cardiac arrhythmia ablation with the novel
      MediGuideTM non-fluoroscopic catheter tracking system in North America. This new
      technology uses electromagnetic field to track sensor integrated intracardiac
      electrophysiology catheters which are projected on pre-recorded fluoroscopy cine
      loops. This new technology permits catheter tracking in virtual biplane
      fluoroscopy and enhances spatial resolution of conventional 3D mapping systems
      while drastically reducing radiation exposure.

PMID- 28496781
TI  - The Role of Echocardiography as a Predictor of the Incidence and Progression of
      Atrial Fibrillation.
AB  - Atrial fibrillation is the most frequent sustained arrhythmia and is an
      independent risk factor for stroke and death. In recent years, major
      echocardiographic advances have been made with the development of new techniques
      and applications that can be extremely useful for the management of these
      patients. This paper describes the role of echocardiography as a predictor of the
      incidence and progression of atrial fibrillation. A detailed description of the
      most relevant studies and recognition of unresolved questions regarding this
      subject are presented here. A special emphasis will be given on new techniques
      that allow the assessment of myocardial deformation and their possible role in
      the way we treat these patients.

PMID- 28496783
TI  - World Atrial Fibrillation Awareness Day - It's About Time!

PMID- 28496784
TI  - Differences of BiAtrial Substrate Properties in Patients with Different Types of
      AF.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in
      clinical practice and induces cardiac dysfunction and strokes. The development of
      AF requires a"trigger" and also an electroanatomic "substrate" capable of both
      initiating and perpetuating AF. Over the past decade, the understanding of the AF
      substrate properties in both atria has increased with fractionation and frequency
      analyses of the local atrial electrograms using three-dimensional electroanatomic
      mapping systems. The purpose of this review was to discuss the differences in the
      atrial substrate properties in patients with different types of AF.

PMID- 28496785
TI  - Body Mass Index, Quality of Life, and Catheter Ablation in Patients with Atrial
      Fibrillation.
AB  - Atrial fibrillation and obesity are interlinked epidemics and both impair quality
      of life. As the prevalence of both conditions in the US continues to rise, so
      will the number of obese patients with atrial fibrillation referred for catheter
      ablation. Catheter ablation has already been shown to significantly improve
      quality of life in patients with atrial fibrillation. Until recently, there has
      been little attention to the effects of catheter ablation on quality of life
      specifically in obese patients with atrial fibrillation. This paper will review
      what is known about the effects of atrial fibrillation and obesity on quality of
      life and how quality of life is affected by catheter ablation for atrial
      fibrillation in obese patients.

PMID- 28496786
TI  - How Does Alcohol Intake Relate to the Risk of Atrial Fibrillation?
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The
      close relationship between acute excesses of alcohol and the occurrence of AF
      even in healthy individuals has been known for several decades. More recently, a
      significant relationship has been consistently observed between elevated
      consumption of alcoholic beverages on a regular basis and an increased risk of
      developing AF. However, the amount of alcohol needed to confer an increased risk
      of AF is rather elevated, approximately two alcoholic beverages per day in women
      and four to five alcoholic beverages per day in men, suggesting that on a
      population level, alcohol is not a major contributor to the global AF epidemic.

PMID- 28496787
TI  - Sarcoidosis Masquerading as Atrial Fibrillation: Interesting Case Discussion as
      Well as Recent Advances in Diagnosis and Management of Cardiac Sarcoidosis.
AB  - This report presents a case of cardiac sarcoidosis initially manifested with
      atrial fibrillation. This behavior is very uncommon in spite of the fact that the
      disease is multisystemic, affecting predominantly the lungs. It is emphasized
      that the diagnosis of the cardiac involvement is difficult, and when this occurs,
      can lead to conducting system disturbances, heart failure or sudden death (SD).
      The diagnosis can be made by evaluating the clinical manifestations, the
      noninvasive tests like ECG, Holter monitoring, chest radiography, thoracic
      computed tomography, magnetic resonance image and positron emission tomography.
      In general, sarcoidosis is treated with steroid compounds with good outcome,
      mainly when performed in the initial phases of the disease. Other cardiac
      manifestations, such as arrhythmias, atrioventricular block or heart failure, are
      managed similar to other cardiomyopathies.

PMID- 28496788
TI  - Respiratory Cycle-Dependent Atrial Trachycardia; its Unique Characteristics and
      Relation with Autonomic Nerve System.
AB  - Respiration influences the sinus heart rate, however, little is still known about
      the tachyarrhythmias related to respiration. Atrial tachycardia (AT) rarely
      emerges during inspiration and it also ceases during expiration. This type of AT
      is thus called respiratory cycle-dependent atrial tachycardia (RCAT), and it
      demonstrates a centrifugal activation pattern. Based on these peculiar P wave
      morphologies, the foci converged either around the right superior pulmonary vein
      (RSPV) or inside the superior vena cava where the anterior right ganglionated
      plexi (ARGP) is considered to be located. The mechanism of such AT is therefore
      thought to be related to the activity of the autonomic system.

PMID- 28496789
TI  - Rate Control in Atrial Fibrillation: Avoiding Morbidity.

PMID- 28496790
TI  - Interdependent Relationship Between Atrial Fibrillation and Sinus Rhythm at the
      Hypothetical Interface of Atrial Fibrillation, Autonomic Tone, Sinoatrial Node
      and Inflammation : Analytical Review, Reconsiderations, Speculations and New
      Insights.
AB  - Underlying mechanisms of atrial fibrillation occurrence and its self
      extinguishing remain not completely investigated yet. The role of autonomic tone
      and sinoatrial node in the interplay between atrial fibrillation and sinus rhythm
      is also not fully understood. The influence of inflammation as a possible source
      of arrhythmia and likelihood of its pharmacologic treatment deserves special
      attention. These complex issues are important for better understanding of
      arrhythmogenesis and rhythm control. Conceptual reconsiderations through the new
      insights primarily on the hypothetic basis may delineate new therapeutic and
      preventive strategies. The aim of this analytical review was to reinforce the
      clinical and laboratory studies regarding the role of: 1) autonomic tone and
      sinoatrial node in restitution of sinus rhythm, 2) new concept of ?vibrantly
      quiescent stroboscopic tuning? as a matured status of atrial fibrillation being
      prepared for its abruption by slight impulse, 3) inflammation in the interplay
      between atrial fibrillation and sinus rhythm, 4) anti-inflammation and anti
      allergic therapy to prevent and to treat the arrhythmia.

PMID- 28496791
TI  - Reversal of Dilated Cardiomyopathy After Successful Radio-Frequency Ablation of
      Frequent Atrial Premature Beats, a New Cause for Arrhythmia-Induced
      Cardiomyopathy.
AB  - Incessant atrial premature beats as a potential cause for tachycardia-induced
      cardiomyopathy was suspected in a patient presenting with dilated non-ischemic
      cardiomyopathy and severely altered left ventricular ejection fraction. The
      elimination of a left atrial focus by percutaneous RF ablation led to
      normalization of the clinical status, of atrial and ventricular dimensions and
      left ventricular systolic function.

PMID- 28496792
TI  - Role of Left Ventricular Diastolic Dysfunction in Predicting Atrial Fibrillation
      Recurrence after Successful Electrical Cardioversion.
AB  - The role of left ventricular (LV) diastolic dysfunction in predicting atrial
      fibrillation (AF) recurrence after successful electrical cardioversion is largely
      unknown. Studies suggest that there may be a link between abnormal LV compliance
      and the initial development, and recurrence of AF after electrical cardioversion.
      Although direct-current cardioversion (DCCV) is a well-established and highly
      effective method to convert AF to sinus rhythm, it offers little else beyond
      immediate rate control because it does not address the underlying cause of AF.
      Preservation of sinus rhythm after successful cardioversion still remains a
      challenge for clinicians. Despite the use of antiarrhythmic drugs and serial
      cardioversions, the rate of AF recurrence remains high in the first year. Current
      evidence suggests that diastolic dysfunction, which is associated with atrial
      volume and pressure overload, may be a mechanism underlying the perpetuating
      cycle of AF recurrence following successful electrical cardioversion. Diastolic
      dysfunction is considered to be a defect in the ability of the myofibrils, which
      have shortened against a load in systole to eject blood into the high-pressure
      aorta, to rapidly or completely return to their resting length. Consequently, LV
      filling is impaired and the non-compliant left ventricle is unable to fill at low
      pressures. As a result, left atrial and pulmonary vein pressure rises, and
      electrical and structural remodeling of the atrial myocardium ensues, creating a
      vulnerable substrate for AF. In this article, we review the current evidence
      highlighting the association of LV diastolic dysfunction with AF recurrence after
      successful electrical cardioversion and provide an approach to the management of
      LV diastolic dysfunction to prevent AF recurrence.

PMID- 28496793
TI  - Co-existence of Atrial Fibrillation with Myocardial Infarction - Unhealthy
      Combination.
AB  - Atrial fibrillation (AF) is the most common arrhythmia with increasing prevalence
      and incidence. As our population ages, modern treatment options and decreased
      case-fatality of cardiovascular diseases are likely to increase the number of
      patients at risk for AF. AF is a frequent co-existing complication ofmyocardial
      infarction (MI). The onset of AF in the setting of AMI requires immediate
      intervention which should be individualized for each patient. AF associated with
      MI influences the in-hospital, medium- and long-term mortality. This brief
      review, based on 41 reports published between 1970 and 2011, focuses on incidence
      and mortality in patients with AF in MI setting. Possible mechanisms of AF in MI
      and treatment options are also discussed.

PMID- 28496794
TI  - Operative Technique and Atrial Tachyarrhythmias After Orthotopic Heart
      Transplantation.
AB  - There is conflicting evidence that operative technique affects the risk of atrial
      tachyarrhythmia after orthotopic heart transplantation (OHT). We sought to
      determine whether OHT by bicaval (BC) technique is associated with a lower risk
      of atrial tachyarrhythmia than biatrial (BA) technique. Consecutive patients who
      underwent OHT between 1997 and 2007 at the University of Minnesota were included
      in this retrospective cohort study with follow-up through December 31, 2011. We
      included 260 OHT recipients (BA, 155; BC, 105). Fifty-nine patients (22.7%)
      developed early atrial tachyarrhythmias. The multivariable odds ratio (95%
      confidence interval [CI]) of BC technique for early atrial tachyarrhythmias was
      0.85 (0.46-1.57), P=0.59. After a median follow-up of 4.9 years, 40 (15.4%)
      patients developed late atrial tachyarrhythmias. The multivariable hazard ratio
      (HR) (95% CI) of BC technique for late atrial tachyarrhythmias was 0.99 (0.50
      1.96), P=0.98. Graft rejection was found to be a multivariate predictor of late
      atrial tachyarrhythmias (HR, 2.89; 95% CI, 1.48-5.65; P=0.002). In contrast to
      prior reports, we did not find an association between operative technique and
      early or late atrial tachyarrhythmias after OHT. Graft rejection is a risk factor
      for late atrial tachyarrhythmias after OHT.

PMID- 28496796
TI  - Subclinical Hypothyroidism: An Overlooked Cause of Atrial Fibrillation?

PMID- 28496795
TI  - Atrial Remodelling : Role in Atrial Fibrillation Ablation.
AB  - There have been considerable advances in understanding the relationship of atrial
      fibrillation (AF) and atrial remodelling suggesting that remodelling states have
      a significant impact on treatment results. Therefore, we reviewed the literature
      about the role of atrial remodelling in AF treatment, focussing on AF ablation.
      Atrial fibrillatory activity, dominant frequencies (DF), complex fractionated
      atrial electrograms (CFAE) as well as function, volume, and fibrosis of the -
      especially left - atrium are most important characteristics for electrical,
      contractile, and structural remodelling predicting success of AF treatment. In
      particular, the results of AF ablation, either using catheter-based or surgical
      techniques, predominantly depend on the degree of structural remodelling, namely
      dilatation and fibrosis of the left atrium. The available data suggest that
      recognizing parameters of remodelling as predictors for AF treatment facilitates
      differentiation between patients who may or may not benefit from the procedure
      and individualization of AF treatment by adapting lesion sets, by ablating
      additional targets, by reducing left atrial size, or by applying extended
      pharmacological treatment.

PMID- 28496797
TI  - Omega-3 Polyunsaturated Fatty Acid Supplementation: Mechanism and Current
      Evidence in Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with
      considerable morbidity and mortality. Available pharmacologic antiarrhythmic
      therapies are often ineffective in preventing the recurrence of AF, possibly
      because these drugs target a single pathophysiological mechanism. Given their
      beneficial effects on ventricular arrhythmias, omega-3 polyunsaturated fatty
      acids (n-3 PUFAs) have recently been investigated as possible candidates in the
      treatment of supraventricular arrhythmias. In this review, we explore the current
      understanding of the antiarrhythmic effects attributed to n-3 PUFAs including
      direct modulation of ionic channels, improvement of membrane fluidity, anti
      inflammatory and antifibrotic effects, and modulation of sympatho-vagal balance.
      We will then focus on the results of epidemiologic studies exploring the
      associations between nutritional intake of n3 PUFAs and the incidence of AF, and
      will review the findings of the clinical trials investigating the effects of n-3
      PUFAs supplementation in the prophylaxis of AF and in the prevention of its
      recurrences.

PMID- 28496798
TI  - Impact of Atrial Fibrillation On Cardiovascular Mortality in the Setting of
      Myocardial Infarction.
AB  - Atrial fibrillation (AF) commonly occurs in patient with acute myocardial
      infarction (AMI). Potential triggers for AF development in this setting includes
      reduced left ventricular function, advanced diastolic dysfunction and mitral
      regurgitation leading to elevated left atrial pressures and atrial stretch. Other
      triggering mechanisms include inflammation and atrial ischemia. Multiple studies
      have shown that AF in patients with is associated with increased mortality.
      However, whether AF is a risk marker or a causal mediator of death remains
      controversial. There is relative dearth of data with regard to optimal management
      of AF in the setting of acute coronary syndromes. Patients with AMI who develop
      AF are at increased risk of stroke. However, the issue of the most appropriate
      antithrombotic regimens is complex given the need to balance stroke prevention
      against recurrent coronary events or stent thrombosis and the risk of bleeding.
      Presently, 'triple therapy' consisting of dual antiplatelet agents plus oral
      anticoagulants for 3-6 months or longer has been recommended for patients at
      moderate-high risk of stroke. Atrial fibrillation (AF), the most common sustained
      arrhythmia seen in clinical practice, often coincides with acute myocardial
      infarction (AMI), with a reported incidence ranging between 7% and 21%.[1] The
      development of atrial fibrillation in the acute phase of AMI may aggravate
      ischemia and heart failure, lead to clinical instability and adversely affect
      outcome. In the following we will review the pathophysiology, clinical
      characteristics and importance, and management of AF occurring in the setting of
      AMI.

PMID- 28496799
TI  - The 894G Allele of the Endothelial Nitric Oxide Synthase 3 (eNOS) is Associated
      with Atrial Fibrillation in Chronic Systolic Heart Failure.
AB  - BACKGROUND: Atrial fibrillation (AF) in patients with heart failure signals poor
      prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in
      the counterregulation of oxidative stress, which is related in part to AF
      pathogenesis. The purpose of this study was to investigate a possible clinical
      association in heart failure patients between the presence of exon 7 G894T eNOS
      polymorphism, known to result in the Glu298Asp protein variant, and the
      occurrence of AF. METHODS: We analyzed the DNA of 344 patients with chronic
      systolic heart failure for exon 7 G894T eNOS polymorphism, using PCR. Odds ratios
      for AF were calculated for the homo- and heterozygous G-allele G894T variants
      relative to the TT variant. RESULTS: Of the 344 patients, 204 (59%) were
      homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were
      homozygous for the T allele. AF episodes were documented in 73 patients (36%)
      with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio
      for AF, based on the presence of at least one G allele in the eNOS 894 gene, was
      3.96 (95% confidence interval, 1.17-13.56, p=0.04). Having two G alleles
      increased the odds ratio to 4.5 (95% confidence interval, 1.0-20.0, p=0.02).
      CONCLUSION: Patients with systolic heart failure demonstrate strong correlation
      between AF and the presence of a G allele in the exon 7 G894T eNOS genotype.
      These findings support the importance of eNOS polymorphism in the pathogenesis of
      AF in heart failure patients.

PMID- 28496800
TI  - Our Mission Towards Atrial Fibrillation Free World.

PMID- 28496801
TI  - 1st International Symposium on Left Atrial Appendage.

PMID- 28496802
TI  - Amiodarone Induced Thyrotoxicosis - Fluctuating RVOT and LV Scar VT.
AB  - A 61 year old patient with non-ischemic cardiomyopathy and implantable
      cardioverter defibrillator presented with multiple shocks for ventricular
      tachycardia (VT). EKG revealed monomorphic sustained VT which was left bundle
      inferior axis that spontaneously changed into sustained VT which was right bundle
      superior axis. This was suggestive of an outflow tract VT transforming into a VT
      probably related to reentry from LV scar. The patient was transferred to our
      university for VT ablation. However, further investigation revealed amiodarone
      induced hyperthyroidism which was the cause of his ventricular tachycardia storm.
      Reversible causes of VT should be considered before proceeding with
      radiofrequency ablation.

PMID- 28496803
TI  - New Stroke Prophylaxis Options in Atrial Fibrillation Patients.
AB  - Atrial Fibrillation (AF) is an epidemic that is increasing in size and scope. AF
      can have many symptoms and cause a variety of negative health impacts.The most
      important health risk of AF is the increased risk of stroke and systemic
      thromboembolism.Oral anticoagulation with warfarin has been the gold standard for
      stroke risk reduction in AF, but new drugs and treatment strategies for AF are
      changing clinical practice. These new advances could offer better tailoring of
      treatments to patients with high risk of stroke while reducing the potential
      bleeding complications.

PMID- 28496804
TI  - Atrial Fibrillation in Patients with Ischemic and Non-Ischemic Left Ventricular
      Dysfunction.
AB  - Atrial fibrillation (AF) and left ventricular dysfunction (LVD) are increasingly
      common clinical problems, affecting millions of people worldwide. It is well
      established that the presence of AF portends a poor prognosis in the setting of
      both ischemic and non-ischemic LVD, and frequently results in worsening clinical
      status. Many clinical studies and trials have attempted to address treatment
      options and efficacy; despite this treatment for AF in LVD is still
      controversial.

PMID- 28496805
TI  - Primary Prevention of Atrial Fibrillation - The Path Untread.
AB  - The prevalence and incidence of atrial fibrillation (AF) is on the rapid rise. To
      slow down the AF epidemic, effective primary prevention strategies need to be
      instituted. Unfortunately, this is an area that has not been well-explored. There
      is a multitude of risk factors that predispose to the development of AF. Of
      these, the most common from an epidemiologic perspective are advanced age,
      hypertension, diabetes, ischemic heart disease, and heart failure. The first-line
      pharmacologic therapies for these predisposing conditions (e.g. beta blockers,
      renin-angiotensin system inhibitors, statins, and omega-3 fatty acids) appear to
      also have potential roles in the primary prevention of AF. Definitive data,
      however, is lacking as to efficacy of these drugs for this particular purpose.
      Large-scale, high-quality randomized clinical trials on AF primary preventive
      strategies are urgently required in order to guide clinical practice. For now,
      adherence to the guideline-based therapies of each individual risk factor appears
      to be the most reasonable approach for the primary prevention of AF.

PMID- 28496806
TI  - Is An Atrial Defibrillator Still An Option In Treating Patients With Atrial
      Fibrillation?
AB  - Atrial fibrillation (AF) is a common disorder associated with significant
      morbidities and presents several challenges for the control of symptoms and
      prevention of long-term implications. Atrial defibrillators (ADs), used for
      rhythm control in patients with symptoms refractory to medical therapy, can
      detect recurrences of the arrhythmia, allow prompt patient-directed treatment,
      and have the potential to reduce hospitalizations and improve quality of life.
      The efficacy of this form of therapy is highest in patients with paroxysmal AF,
      and with the use of a coronary sinus shocking lead. While R-wave synchronized
      shocks are a prerequisite for a safe use, the procedure is well tolerated and
      usually not associated with long-term psychological side effects. Limitations of
      ADs include acute and chronic complications related to cardiac rhythm device
      implantation, the requirement in some cases for more than one shock to terminate
      AF, the discomfort from shocks, as well as the need for sedation to alleviate
      pain from the shocks. With the ever-expanding role of catheter-based therapies
      for AF, it seems that the role of ADs in this regard is rather limited.

PMID- 28496807
TI  - Prophylactic Antiarrhythmic Drug Therapy in Atrial Fibrillation.
AB  - In patients with recurrent atrial fibrillation (AF), the hallmark of treatment
      has been the use of antiarrhythmic drugs (AADs). Goals of therapy include
      reduction in the frequency and duration of episodes of arrhythmia as well an
      emerging goal of reducing mortality and hospitalizations associated with AF.
      Safety and efficacy are important factors when choosing an antiarrhythmic drug
      for the treatment of AF, hence, if AAD are required for maintenance of sinus
      rhythm, their safety profi le, together with individual patient characteristics,
      should be of utmost concern. In the next paragraphs we would like to review some
      aspects (electrophysiologic effects, metabolism, side effects, current evidence
      and indication) of the most commonly used AAD for the management of patients with
      AF, following the Vaughan-Williams classification. However, this system is mainly
      based on ventricular activity, therefore, and due to its relatively atrial
      selective actions, some agents will not readily fit in the Vaughan Williams AAD
      classification. For that reason, in the final part of the manuscript, new
      promising agents will be reviewed separately.

PMID- 28496809
TI  - Catheter Ablation of Long Standing Persistent Atrial Fibrillation: Lessons
      Learned.
AB  - Atrial fibrillation has evolved from being a novel unproven procedure to being an
      important treatment option for patients with symptomatic atrial fibrillation.
      Atrial fibrillation ablation is an appropriate treatment option for patients with
      symptomatic atrial fibrillation, particularly if they have failed one or more
      trials of antiarrhythmic drug therapy. While much has been learned about the
      optimal technique and outcomes for catheter ablation of paroxysmal atrial
      fibrillation; catheter ablation of atrial fibrillation in patients with long
      standing persistent atrial fibrillation remains in its infancy. The following
      objectives would be accomplished in this review article. First, we will review
      the various ablation strategies, which have been employed and proposed for
      ablation of long standing persistent atrial fibrillation. Second, the
      methodology, results and outcomes of the major studies were reviewed in detail,
      which have reported outcomes of ablation in this patient population. And finally,
      some conclusions were drawn regarding where we stand and where the knowledge gaps
      remain as we seek to improve ablation outcomes in this population of AF patients.

PMID- 28496808
TI  - The Relationship Between Pericardial Fat and Atrial Fibrillation.
AB  - Pericardial adiposity is strongly associated with increased cardiovascular risk,
      especially for coronary artery disease. However, until 2010 researchers have not
      focused on the mechanistic role of pericardial fat in atrial fibrillation (AF)
      pathogenesis. Only a limited number of studies have reported on the significant
      association between pericardial fat and AF prevalence, and the role of
      pericardial fat on AF chronicity and symptom burden remain an ongoing debate.
      Several possible mechanisms associating pericardial fat with increased AF
      prevalence have been suggested, but no prior studies have definitively elucidated
      the precise role of pericardial adiposity on increased AF risk. Currently,
      pericardial fat has recently emerged as a new independent AF risk factor. In this
      brief review, we discuss several potential mechanisms that might associate
      pericardial fat to AF pathogenesis.

PMID- 28496810
TI  - Prevention of Stroke by Antithrombotic Therapy in Patients with Atrial
      Fibrillation.
AB  - Atrial Fibrillation (AF) is the most common clinically significant sustained
      cardiac arrhythmia, a major risk factor for strokes whether it is symptomatic or
      silent. The older CHADS2 score and the newer CHADS2-VASc are well validated to
      determine stroke risk and guide initiation of antithrombotic therapy, but
      haemorrhagic risk has to be respected as well, and scores such as HAS-BLED should
      be widely used. Old fashioned warfarin became standard of care outperforming
      antiplatelets in every trial but novel classes of anticoagulants that overcome
      many of warfarin drawbacks have been introduced and are already guideline
      recommended regiments. Nevertheless their use poses new questions that have to
      been answered in the near future.

PMID- 28496811
TI  - The Temporal Relationship Between Atrial Fibrillation and Ischemic Stroke.
AB  - It is well established that the presence of atrial fibrillation (AF) is
      associated with an increased risk of stroke; however, the precise role that AF
      plays in increasing this risk is less well understood. In particular, it is not
      fully known whether a temporal relationship between AF and stroke exists. Early
      clinical trials in this field were limited by their rudimentary tools for
      monitoring of AF recurrences. More recently, studies employing implantable
      cardiac rhythm devices have brought greater precision to our ability to
      accurately detect and quantify episodes of AF but have been restricted to patient
      populations with clinical indications for those types of devices.In the future,
      new monitoring modalities such as subcutaneous devices and external patches may
      allow us to extend precise arrhythmia monitoring to the broader AF population.
      Due to the relatively low rate of clinical events, large clinical trials or
      registries will be required to fully appreciate the temporal aspects of AF and
      stroke and alternative metrics for quantifying AF recurrences need to be
      explored.

PMID- 28496812
TI  - Catheter Ablation of Atrial Fibrillation to Maintain Sinus Rhythm.
AB  - Catheter ablation of atrial fibrillation (AF) is an important treatment modality
      for patients with AF. Although the superiority of catheter ablation of AF over
      antiarrhythmic drug therapy has been demonstrated in middle aged patients with
      paroxysmal AF, the role of catheter ablation in other patient subgroups,
      particularly in the elderly, those with heart failure, and those with long
      standing persistent AF has not been as well defined. Furthermore, although AF
      ablation can be performed with reasonable efficacy and safety in experienced
      hands, late recurrences of AF a year or more following AF ablation are not
      uncommon. Fortunately the techniques and tools used for AF ablation continue to
      evolve and it is likely that the outcomes of AF ablation will improve further in
      the future.

PMID- 28496813
TI  - Atrial Fibrillation in Patients with Cardiac Resynchronization Therapy: Clinical
      Management and Outcome.
AB  - Atrial fibrillation (AF) and heart failure (HF) are two emerging epidemics in the
      cardiovascular field and are strictly inter-related since may directly predispose
      to each other. Cardiac resynchronization therapy (CRT) has emerged as an
      important therapeutic option for selected HF patients with LV dysfunction and
      ventricular dyssynchrony. However almost all RCTs demonstrated the CRT
      effectiveness in patients in sinus rhythm (SR), including permanent AF among the
      exclusion criteria. In patients with paroxysmal or persistent AF strategies for
      rhythm control can be applied, but usually with limited efficacy. Furthermore,
      rhythm control strategy did not result superior to rate-control in patients with
      heart failure. AF ablation in HF patients is usually performed only in selected
      centres. In patients with permanent or long-standing AF and a CRT device the
      option of AVN ablation offers the advantage of allowing >95% biventricular
      pacing. AF implies a harmful increase in thromboembolic risk. Detection of AF in
      patients treated with a CRT device is enhanced by device diagnostic capabilities,
      that allow detection of episodes of atrial tachyarrythmias, including silent AF.
      In these cases decision making on appropriate antithrombotic prophy/laxis has to
      consider clinical risk stratification, usually applying CHADS2 and CHA2DS2VASc
      scores. In summary, in order to maximise outcome, AF in patients with CRT prompts
      the need to appropriately decide on antithromboembolic prophylaxis (according to
      risk stratifications), as well as on rate and/or rhythm control strategies, with
      the aim to allow constant biventricular pacing. In this perspective, AVN ablation
      has an important role since by inducing pace-maker dependency guarantees
      continuous biventricular pacing.

PMID- 28496815
TI  - The Relationship Between Physical Activity and Risk of Atrial Fibrillation-A
      Systematic Review and Meta-Analysis.
AB  - Aim: The aim of this systematic literature review and meta-analyses was to
      explore the relationship between physical activity and risk of new-onset atrial
      fibrillation (AF) or flutter (AFlu). Results: The search revealed 10 published
      studies that were eligible for three different meta-analyses. A meta-analysis of
      six case-control studies showed that risk of AF increased more than 5-fold in
      athletes compared to non-athletic controls, OR=5.3 [(3.6, 7.9; 95% confidence
      interval (CI)], p<0.0001. A second meta-analysis of three case-control studies
      showed a significantly higher prevalence of athletes among AF populations
      compared to their healthy controls, OR=4.7 (3.1-6.9; 95% CI), p<0.0001. A third
      meta-analysis of three prospective large-scale long-term studies showed that
      moderate/high habitual physical activity was associated with significantly
      reduced risk of AF compared with none or very low intensity physical activity
      OR=0.89(0.83, 0.96; 95% CI), p=002 Conclusions: Long-term vigorous physical
      training or lack of physical activity both are associated with increased risk of
      AF, while habitual moderate physical activity may be associated with reduced
      risk. Further large-scale prospective randomized controlled studies particularly
      in athletes are needed to further confirm these findings.

PMID- 28496814
TI  - Impact of Obstructive Sleep Apnea on Outcomes of Catheter Ablation of Atrial
      Fibrillation.
AB  - : Obstructive sleep apnea (OSA) is a growing epidemic in the United States and
      significantly contributes to the increasing prevalence of atrial fibrillation
      (AF) in the U.S. POPULATION: Although a strong correlation between OSA and AF has
      been demonstrated, a causal relationship between these two conditions has not
      been definitively established. Evidence of OSA is an important consideration of
      AF management and impacts the success rate of catheter ablation. The presence of
      OSA tends to predict a lower success rate and higher complication rate for
      catheter ablation of AF. However, recent studies evaluating OSA as an independent
      risk predictor of AF recurrence following an ablation procedure have yielded
      conflicting results. A greater understanding of these conditions would allow for
      a more specific therapy targeting the type of AF associated with OSA. The
      following review provides a brief summary of obstructive sleep apnea etiology,
      focuses on the relationship between OSA and AF, and discusses the impact of OSA
      on the outcomes of catheter ablation of AF.

PMID- 28496816
TI  - The Role of Pericardial and Epicardial Fat in Atrial Fibrillation Pathophysiology
      and Ablation Outcomes.
AB  - Emerging evidence suggests that epicardial and pericardial fat are related to the
      presence, severity and outcome of AF. These associations, independent of
      generalized obesity, suggest that they may become increasingly useful as markers
      for risk stratification or monitoring in the clinical setting. Mechanistically,
      studies have suggested the effects of epicardial and pericardial fat may be
      mediated by local adipokines, inflammation, fatty infiltration, modulation of AF
      drivers and left atrial dilatation. Given the dual epidemics of AF and obesity,
      in the present paper we review the role that the ectopic adipose tissue
      surrounding the heart has in the pathogenesis of AF. Further inquiries in this
      active area of investigation may ultimately lead to new insights in how to best
      combat these interrelated epidemics and reduce the societal burden of AF.

PMID- 28496817
TI  - Impact of Metabolic Syndrome on Ablation-Outcome in Patients with Atrial
      Fibrillation: A Systematic Review.
AB  - Metabolic syndrome (MS), a pro-inflammatory state with hypertension, diabetes,
      dyslipidemia and obesity is presumed to be a close associate of atrial
      fibrillation (AF). However, the exact mechanism by which MS facilitates
      perpetuation of AF is yet to be fully understood. Moreover, the impact of the
      components of MS as well as MS as a group, on ablation-outcome in AF is not
      clearly elucidated until now. This review has compiled the results from major
      studies that have looked into those risk factors and defined their significance
      in influencing ablation-outcome in AF. It has also overviewed the impact of life
      style changes that might improve the success rate of AF-ablation by effectively
      addressing the different constituents of MS.

PMID- 28496819
TI  - How Much Exercise Is Too Much.

PMID- 28496818
TI  - Risk Factors for Post-Coronary Artery Bypass Grafting (CABG) Atrial Fibrillation
      and the Role of Aspirin and Beta Blockers in its Prevention.
AB  - Background: Atrial fibrillation/flutter (AF) is the most common arrhythmia
      following coronary artery bypass grafting (CABG) and it increases morbidity and
      mortality associated with this procedure. The purpose of this study was to
      evaluate the predictability of this arrhythmia using previously identified risk
      factors and to assess the efficacy of recommended prophylactic beta blocker (BB)
      therapy in the prevention of post CABG AF. Methods: We performed a retrospective
      chart analysis of consecutive patients undergoing elective CABG during 1 year
      period. Patients who developed new onset AF after the surgery were designated as
      cases and those who did not, as controls. 41 different variables were analyzed
      using Chi-square test and independent sample t-test. Multivariate analysis was
      carried out using logistic regression model. Results: 23% patients undergoing
      CABG developed AF during post-operative period. Statistically significant
      differences were observed between the two groups in terms of age, use of peri
      operative Aspirin (ASA), current smoking, previous history of AF, left atrial
      size, history of congestive heart failure (CHF) and brain natriuretic peptide
      (BNP) levels. In terms of prophylactic therapy, preoperative BB did not
      independently protect against post CABG AF. On multivariate analysis, only age,
      use of ASA and previous history of AF remained as independent predictors of post
      CABG AF. Conclusion: In our study population, the use of preoperative BB did not
      independently decrease the risk of post-CABGAF. Age, peri-operative ASA use and
      previous history of AF remained strong independent predictors of post- operative
      AF.

PMID- 28496820
TI  - Boston AF Symposium Moves to Orlando !

PMID- 28496821
TI  - Emergency Physician Patterns Related to Anticoagulation of Patients with Recent
      Onset Atrial Fibrillation and Flutter.
AB  - Guidelines strongly recommend long-term anticoagulation with warfarin for
      patients with newly recognized AF who have high embolic risk by virtue of a
      CHADS2 (Congestive Heart Failure, Hypertension, Age >65, Diabetes, History of
      Stroke) score >= 2. The goal of this study was to determine patterns of emergency
      department-initiated anticoagulation among eligible patients discharged from
      Canadian centers with an episode of recent-onset atrial fibrillation and flutter
      (RAFF) and determine if decision-making is driven by the CHADS2 score or other
      factors. This was accomplished by examining health records using uniform case
      identification and data abstraction as well as centralized quality control; it
      was conducted in 8 Canadian university emergency departments over a 12-month
      period. Eligible patients for this analysis demonstrated RAFF requiring emergency
      management, were not already taking warfarin and were not admitted to hospital.
      Univariate analyses were conducted using T-test or Chi-square to select factors
      associated with anticoagulation initiation at a significance level of p < 0.15
      and multiple logistic regression was employed to evaluate independent predictors
      after adjustment for confounders. Among 633 eligible patients, only 21 out of 120
      patients (18%) with a CHADS2 score >= 2 received anticoagulation and among 70
      patients who were given anticoagulation only 21 (30%) had a CHADS2 score >= 2.
      Independent predictors of anticoagulation included age by 10-year strata: (OR =
      1.7; 95% CI 1.3 - 2.1), heparin use in the anticoagulation (OR = 9.6; 95% CI 4.9 
      18.9), a new prescription for metoprolol (OR = 9.6; 95% CI 4.9 - 18.9) and being
      referred to cardiology for follow-up (OR = 5.6; 95% CI 2.6 - 12.0). CHADS2 >= 2
      doubled the likelihood of being prescribed anticoagulation (OR= 2.0; 95% CI 1.5 -
      3.5) but was not an independent predictor. It was thus determined that patients
      discharged from the emergency department in this study were not prescribed
      anticoagulation in keeping with current recommendations. This practice gap merits
      further investigation and may benefit from educational efforts or enhanced
      support for anticoagulation use from the emergency department.

PMID- 28496822
TI  - Prerequisites for Exploring Predictors of Chronic Atrial Fibrillation Recurrence
      After Ablation.
AB  - The ablation treatment for the atrial fibrillation extends to the persistent
      atrial fibrillation now. However, the cure rate of persistent atrial fibrillation
      by Radiofrequency Ablation is lower than paroxysmal atrial fibrillation and we
      really want to know is the information that what kind of persistent atrial
      fibrillation ablation therapy is effective for. Therefore, it is wished the
      predictors of recurrence after the ablation for the persistent atrial
      fibrillation is confirmed, but does not yet confirm. The cause that is not
      confirmed seems to be present in many factors including the gene which the atrial
      fibrillation occurs in and persist, the change of pathology into remodeling
      according to progression of atrial fibrillation and strategy of the ablation
      corresponding to them. Left atrium diameter, Duration of atrial fibrillation and
      Cardiac Function that are involved deeply in atrial muscle and electric
      remodeling, and Ablation strategy corresponding to them are considered based on
      the conventional report. It can be stated now, however, that persistent atrial
      fibrillation patients with some degree (although this "some degree" has not been
      clearly defined) of enlarged left atrium diameter, prolonged atrial fibrillation
      duration, or decreased cardiac function may also revert to sinus rhythm with
      Radiofrequency Ablation, more efficient treatment may be developed in the future
      and reversion to sinus rhythm may increase the benefit to patients. In summary,
      RF ablation for persistent AF is currently required with further study of the
      predictors of recurrence after the ablation for the persistent atrial
      fibrillation.

PMID- 28496823
TI  - Prediction of Atrial Fibrillation by B-type Natriuretic Peptide.
AB  - Background: Although several conditions have been proposed as risk factors
      contributing to the incidence of atrial fibrillation, many individuals without
      such 'risk factors' also suffer from atrial fibrillation. The present study
      tested the hypothesis that the risk of new-onset atrial fibrillation increases
      with increasing circulating levels of B-type natriuretic peptide in the general
      population. Methods: Participants in our health checkup program without atrial
      fibrillation or a history of atrial fibrillation were enrolled (n=10,058, 54.3+/
      11.3 years old). After baseline evaluation, subjects were followed up for the
      median of 1,791 days with the endpoint being the new onset of atrial
      fibrillation. Results: Atrial fibrillation occurred in 53 subjects during the
      follow-up period (1.16 per 1,000 person-year). The risk of new-onset atrial
      fibrillation increased across the gender-specific quartiles of B-type natriuretic
      peptide levels at baseline. In multivariate Cox proportional hazard regression
      analysis where B-type natriuretic peptide concentrations were taken as a
      continuous variable, B-type natriuretic peptide was a significant predictor of
      new onset of atrial fibrillation after adjustment for possible factors (hazard
      ratio 5.65 [95% CI 2.63-12.41]). Conclusions: The risk of new onset of atrial
      fibrillation increases with increasing B-type natriuretic peptide levels in the
      general population. Measurement of B-type natriuretic peptide may improve the
      prediction of incident atrial fibrillation.

PMID- 28496824
TI  - Dronedarone: Where Does it Fit in the AF Therapeutic Armamentarium?
AB  - Dronedarone is a derivative of amiodarone with similar mechanisms of action
      (blocking calcium, potassium and sodium channels in addition to having anti
      adrenergic effects). Compared to amiodarone it has fewer drug interactions
      (though it can interact with all current anticoagulants), more limited risk of
      organ toxicity, a much shorter half-life with no need for a loading regimen, but
      lower efficacy. Dronedarone is approved for the treatment of atrial fibrillation;
      has had limited studies for other arrhythmias; and has no adverse drug-ICD
      interactions reported. Clinical trials have resulted in only one dosing regimen
      (400 mg bid, to be taken with food) and have demonstrated both rate and rhythm
      effects in atrial fibrillation (AF). Dronedarone slows the ventricular response,
      can prolong the time to/reduce recurrences of/ reduce progression of AF, and
      reduce the incidence of hospitalization in AF patients with risk-prone markers.
      However, trials have also revealed an increased risk of mortality and other
      adverse cardiovascular outcomes from dronedarone when given to patients in heart
      failure. The details of these trials, additional pharmacokinetic and
      pharmacodynamic information, and recommendations concerning the use of
      dronedarone are provided in the full manuscript that follows.

PMID- 28496825
TI  - Ischemic Conditioning and Atrial Fibrillation: Hope for a NewTherapy?
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia.It is
      accompanied by both structural and ion channel remodeling which underlie the
      propensity to perpetuate AF.The prevalence of AF is expected to increase as
      population ages and as more patients survival myocardial infarction. Despite
      pharmacological and nonpharmacological (such as ablation) therapies for AF, more
      effective therapy is needed. Ischemic or pharmacological conditioning offers a
      potential novel approach to patients with AF. This review will focus on the basic
      biology of ischemic pre- and postconditioning, patho-physiology of AF,
      potentially novel AF treatment approachs based on conditioning, and clinical
      situations that may be amenable to a conditioning strategy.

PMID- 28496826
TI  - Alternative Therapies in the Treatment of Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most common clinical arrhythmia and represents a
      major social and economic problem. The number of subjects with AF is constantly
      increasing as a result of aging and improved survival in several cardiac and non
      cardiac diseases. Patients with AF are often symptomatic, have a reduced physical
      capacity and are at high risk for thromboembolic events. Moreover, AF is
      associated with increased mortality and independent of the management, based
      either on rhythm or rate control strategy. The safety and efficacy of most anti
      arrhythmic drugs are questionable. Increasing attention has therefore been
      addressed to evaluate the possible therapeutic and/or preventive effects of forms
      of treatment coming from ancient medical traditions of Far East, like acupuncture
      and yoga. In traditional Chinese medicine, acupuncture has been found effective
      in managing patients with paroxysmal supraventricular tachycardia. Recently, also
      in the Western literature, reports have been published supporting the clinical
      efficacy of acupuncture to treat arterial hypertension and to reduce chest pain.
      Other studies have evaluated the effects of acupuncture and other methods of
      Eastern Medicine, i.e., Qigong, Tai Chi Chuan and Yoga, in the treatment of
      cardiac illnesses associated with supraventricular arrhythmias. Two reports on
      the effects of acupuncture in preventing or reducing the rate of AF recurrences
      in patients with persistent or paroxysmal AF have been recently reported .
      Another ancient traditional eastern form of therapy and prevention, i.e., yoga,
      has been recently shown to reduce episodes of atrial fibrillation and improve the
      symptoms of anxiety and depression often associated with this arrhythmia. Growing
      evidence indicates that acupuncture and yoga are safe, without any pro-arrhythmic
      effect and with limited cost. All these factors should be considered when
      evaluating the efficacy of therapeutic intervention for an epidemic disease such
      as AF.

PMID- 28496827
TI  - Left Atrial Anatomy in Patients Undergoing Ablation for Atrial Fibrillation.
AB  - Background: Left atrial anatomy is highly variable, asymmetric, irregular and
      three-dimensionally unique. This variability can affect the outcome of atrial
      ablation. A catalog of anatomic varieties may aid patient selection and ablation
      approach and provide better tools for left atrial ablation. Methods: We analyzed
      computed tomography scans from 514 patients undergoing left atrial ablation.
      Images were processed on Advantage Windows with CardEPTM software (GE Healthcare,
      Waukesha, WI). Measurements of pulmonary vein (PV) ostial size along the long and
      short axes were made using double oblique cuts, and area of the ostia was
      calculated. Results: Patients with 2 left (LPV) and 2 right PVs (RPV) (62.6%), 2
      LPVs and 3 RPVs (17.3%) and 1 LPV and 2 RPVs (14.2%) made up the three most
      common variants. In the 2-LPV/2-RPV anatomy, the ostial size and area of the RPVs
      were larger than their corresponding LPVs (p<0.001), and the ostial size and area
      of the superior PVs were larger than their corresponding inferior PVs (p<0.001).
      In the 2-LPV/3-RPV anatomy, the total area of the RPVs was larger than the total
      area of the LPVs (p<0.001). In the 1-LPV/2-RPV anatomy, the ostial size of the
      left common PV was larger than either right PV (p<0.007). However, the total area
      of the RPVs was larger than the area of the left common PV (p<0.002). The left
      common PV was also larger than any of the left veins in any of the other
      anatomies. The total PV area between the three most common anatomies was not
      significantly different. Conclusions: More than 37% of patients have a left
      atrial anatomy other than 2 left and 2 right PVs. This data may help in designing
      approaches for left atrial ablation, tailoring the procedure to individual
      patients and improving ablation tools.

PMID- 28496828
TI  - The Prevalence of Low Left Atrial Appendage Emptying Velocity and Thrombus in
      Patients Undergoing Catheter Ablation for Atrial Fibrillation on Uninterrupted
      Peri-procedural Warfarin Therapy.
AB  - Introduction: The 2012 HRS/EHRA/ECAS guidelines encourage pre-procedural
      transesophageal echocardiography (TEE) prior to ablation for atrial fibrillation
      (AF), but acknowledge a lack of consensus in patients maintained on therapeutic
      warfarin before, during and after the procedure. This is partly because the
      incidence of left atrial appendage (LAA) thrombus is so low, that it is hard to
      draw clear conclusion regarding the characteristics of patients who develop
      thrombus. We hypothesize that the presence of low LAA emptying velocities, which
      predisposes to thrombus, and/or thrombus itself can be predicted in patients
      undergoing ablation, based upon clinical characteristics and transthoracic
      echocardiography (TTE). Methods: In this multicentre study, we undertook TTE and
      transesophageal echocardiograms (TEE) in 586 patients (age 59.9+/-0.4 years old,
      64.5% male) undergoing catheter ablation for AF who were anticoagulated on
      warfarin (target international normalized ratio 2-3.5) for >=3 consecutive weeks
      prior to procedure and maintained on warfarin for the procedure. Results: Low
      peak LAA emptying velocities (<40cm/s) were identified in 111 (24.7%) patients
      and LAA thrombus was identified in 3 patients (0.5%) despite having therapeutic
      INRs. The 3 patients with thrombus had LAA emptying velocities of 23, 29 and 31
      cm/s. None of the remaining patients had a peri-procedural stroke. Patients with
      peak LAA emptying velocities <40cm/s or thrombus on TEE had significantly
      (p<0.05) higher CHA2DS2-VASc scores (1.7+/- 0.1 v's 1.4+/-0.1), and were more
      likely to have impaired LVSF (odds ratio [95% CI]: 2.66 [1.52-4.66]), a LA
      diameter >4.6cm on TTE (2.40 [2.13-5.41]), or persistent AF (2.60 [1.63-4.14])
      compared to those with a higher LAA velocity without thrombus. Conclusion: In
      patients on uninterrupted warfarin therapy, a CHA2DS2-VASc score >=1 or LA
      diameter >4.6cm on TTE identifies 91.5% of those at risk of developing thrombus
      with LAA emptying velocity of <40 cm/s and 100% of those with thrombus in our
      cohort.

PMID- 28496829
TI  - Post-operative Atrial Fibrillation - Pathophysiology, Treatment and Prevention.
AB  - Atrial fibrillation occurring after cardiac surgery has been the subject of
      intensive research over the past decades. However, the incidence remains high,
      despite numerous preventive and treatment strategies. In addition, several
      reports show that the impact of post-operative atrial fibrillation (POAF) is
      high. It is an independent risk factor for mortality after several years. These
      findings make clear that the pathophysiology of POAF is not fully understood and
      POAF-associated risks to some extent might be underestimated. On the one hand,
      excessive triggers during the acute post operative phase after cardiac surgery
      might initiate AF even in atria with low vulnerability. On the other hand, many
      patients undergoing surgery have an atrial substrate at the time of operation
      promoting AF not only in the post-operative phase but also in the days and weeks
      thereafter. Progress in our understanding of the AF mechanisms in general has
      provided valuable insights into processes involved in atrial structural
      remodeling due to advanced age, hypertension, obesity, and congestive heart
      failure. These patient characteristics strongly contribute to cardiac disease,
      predict POAF and likely have an impact on the risk of thrombus formation in the
      weeks and months after cardiac surgery. For a better understanding of the
      mechanisms involved, it is important to not only recognize the occurrence of POAF
      by continuous monitoring after surgery, but also to identity the extent of atrial
      vulnerability to AF in these patients.

PMID- 28496830
TI  - Role of Intracardiac echocardiography in Atrial Fibrillation Ablation.
AB  - In the recent years, several new evidences support catheter-based ablation as a
      treatment modality of atrial fibrillation (AF). Based on a plenty of different
      applications, intracardiac echocardiography (ICE) is now a well-established
      technology in complex electrophysiological procedures, in particular in AF
      ablation. ICE contributes to improve the efficacy and safety of such procedures
      defining the anatomical structures involved in ablation procedures and monitoring
      in real time possible complications. In particular ICE allows: a correct
      identification of the endocardial structures; a guidance of transseptal puncture;
      an assessment of accurate placement of the circular mapping catheter; an indirect
      evaluation of evolving lesions during radiofrequency (RF) energy delivery via
      visualization of micro and macrobubbles tissue heating; assessment of catheter
      contact with cardiac tissues. Recently, also the feasibility of the integration
      of electroanatomical mapping (EAM) and intracardiac echocardiography has been
      demonstrated, combining accurate real time anatomical information with
      electroanatomical data. As a matter of fact, different techniques and ablation
      strategies have been developed throughout the years. In the setting of balloon
      based ablation systems, recently adopted by an increasing number of centers, ICE
      might have a role in the choice of appropriate balloon size and to confirm
      accurate occlusion of pulmonary veins. Furthermore, in the era of minimally
      fluoroscopic ablation, ICE has successfully provided a contribute in reducing
      fluoroscopy time. The purpose of this review is to summarize the current
      applications of ICE in catheter based ablation strategies of atrial fibrillation,
      focusing-on electronically phased-array ICE.

PMID- 28496831
TI  - Role of Atrio-Ventricular Junction Ablation in Symptomatic Atrial Fibrillation
      for Optimization of Cardiac Resynchronization Therapy.
AB  - Cardiac resynchronization (CRT) therapy is indicated in patients with at least
      mildly symptomatic heart failure, left ventricular ejection fraction <=35% and
      wide QRS, and has been associated with decreased morbidity and mortality.
      Unfortunately, approximately 30% of the patients appropriately selected for
      therapy do not respond to CRT. Among the reasons for non-response, atrial
      fibrillation (AF) plays a prominent role. AF limits the degree of biventricular
      pacing during CRT, not only when the ventricular rate is fast and highly
      irregular, but also during periods of of relatively constant rate, by causing
      fusion and pseudo-fusion complexes. Importantly, achievement of nearly 100%
      biventricular pacing is necessary to derive benefit from CRT. A simple, albeit
      irreversible, method to maximize biventricular pacing in patients with AF who are
      otherwise eligible for CRT is atrioventricular junction (AVJ) ablation. In this
      review, we discuss the role of AVJ ablation in CRT optimization in patients with
      AF. The available evidence from observational non-randomized studies suggests
      that AVJ ablation in patients with AF qualifying for CRT may offer improvement in
      heart failure symptoms, better survival, and better cardiac function. In light of
      the inherent limitations of non-randomized studies, further randomized studies
      are needed to support this treatment option.

PMID- 28496832
TI  - Relationship of Ostial Pulmonary Vein Scar with Reduction in Pulmonary Vein Size
      after Radiofrequency Ablation for the Treatment of Atrial Fibrillation: An
      Observational Cohort Study.
AB  - Background: Radiofrequency (RF) ablation procedures to electrically isolate the
      pulmonary veins (PV) from the left atrium are frequently used to treat atrial
      fibrillation. We hypothesized that changes in PV size after RF ablation would
      correlate with the volume of ostial PV scar as assessed by high resolution late
      gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Methods:
      The study cohort included 23 consecutive subjects. Contrast enhanced PV CMR
      angiography and LGE were obtained before and 42 +/- 18 days after RF ablation.
      Results: A total of 85 PV were analyzed. Imaging after RF ablation demonstrated a
      reduction in PV diameter (22 +/- 7 mm to 21 +/- 6 mm, p = 0.001) and a reduction
      in cross-sectional area (CSA) (285 +/- 141 to 246 +/- 110, p < 0.001). There was
      a significant correlation of PV ostial normalized scar volume with the change in
      PV diameter (r =-0.21, p =0.049) and CSA (r =-0.28, p =0.010) after AF ablation.
      PV in the highest quartile for PV scar had the greatest reduction in diameter and
      CSA (p <0.05 for both). Conclusion: PV size decreases significantly after RF
      ablation for the treatment of AF. The change in PV size is linearly related to
      the quantity of LGE scar at the PV ostium.

PMID- 28496833
TI  - Myocardial Ischemia as a Genuine Cause Responsible for the Organization and
      "Fertilization" of Conflictogenic Atrial Fibrillation:New Conceptual Insights
      Into Arrhythmogenicity.
AB  - Atrial fibrillation continues to be a challenging arrhythmia. There are some
      conventional, time-tested explanations of atrial fibrillation genesis, however
      some uncertainty of its complete understanding still exists. We focused on atrial
      ischemia which, hypothetically, could be responsible for manifestation of the
      arrhythmia, irrespective of the underlying heart disease. Evidences abounds that
      atrial fibrillation has an extremely strong association with
      nutritional/oxidative status of myocardium. This arrhythmia seemingly may stem
      from the electrophysiological differences taking place in the boundary areas. To
      validate such assumptions we have surveyed widely accepted theories based on
      clinical and experimental evidence. There was an attempt to integrate some well
      known theoretical explanations (focal, multifocal, ectopic, reentrant activity,
      atrial remodeling, etc.) into a new conceptually systematized arrhythmogenesis.
      Confronting ischemic and non-ischemic atrial zones electrophysiologically on
      their borderlines presumably creates a substrate vulnerable to the development of
      atrial fibrillation. The behavior of these interrelated areas is likely ischemia
      dependent; the separating borderline(s) may be treated as conflictogenic,
      releasing triggers/drivers to commence and to perpetuate the arrhythmia.
      Ischemically damaged and non-damaged myocardial areas likely participate in the
      relay-race carousel of arrhythmogenicity due to their mutual interactions,
      accompanied by the "fireworks" at the separating borderlines. It could be
      concluded that myocardial ischemia as a nonspecific proarrhythmic factor
      presumably plays a key role in the genesis and sustenance of atrial fibrillation.
      Theoretically the most important step in eradication of arrhythmogenic substrate
      might be an overall abolition of ischemia regardless of the characteristics of
      underlying heart disease. Innovative intellectual and explorative research is
      needed to render innocuous the ischemia that might help us win the century's
      cardioarrhythmological battle.

PMID- 28496836
TI  - Cryo-Balloon Ablation of the Right Superior Pulmonary Vein Involving the Anterior
      Right Ganglionated Plexus for Speech and Breathing Induced Atrial Tachycardia.
AB  - Targeting ganglionated plexi (GP) during catheter ablation of atrial fibrillation
      (AF) is associated with improved outcome. We present a patient with speech and
      breathing induced atrial tachycardia (AT) originating in the superior vena cava
      (SVC) and the right superior pulmonary vein (RSPV), near the anatomical location
      of the anterior right GP (ARGP). The trigger for the arrhythmia appeared to be
      vagal discharge from the GP, possibly induced by local stretch. Ablation with a
      28 mm cryo-balloon advanced to the RSPV orifice through a patent foramen ovale
      (PFO) abolished the arrhythmia, probably involving the underlying parasympathetic
      influx to the SVC and RSPV myocardial sleeves.

PMID- 28496834
TI  - Age-Dependent Impact of Fluoroscopic Radiation on the Gender of Off-Spring: An
      International Survey of Cardiologists.
AB  - Background: Fluoroscopic radiation has been implicated in reducing the sex ratio
      (M:F) by potentially damaging the Y chromosome. We examined the effects of
      exposure to fluoroscopic radiation on gender of offspring of cardiologists across
      the world. Methods: An internet based survey was e-mailed worldwide to 8000
      physicians who practice invasive electrophysiology and/or interventional
      cardiology. Survey questions included age, race, sub-specialty, hours of exposure
      to radiation, number of children, gender of off-spring, miscarriages and
      mutations and exposure to radiation prior to conception of each child. Logistic
      regression analyses were performed on years of exposure and gender of offspring
      born post radiation exposure. Results: Responses of 377 cardiologists (84% male
      and 16% female) were reviewed. With a total of 398 males and 402 females born to
      377 cardiologists, although reduced, the overall sex ratio (0.99) was not
      significantly different from that observed in the general population (1.05).
      Univariate logistic regression analysis identified higher male births with
      increasing hours of radiation exposure (OR 1.034, CI 1.003-1.067 p=0.03) and
      increasing paternal age (OR 1.05, CI 1.01-1.08, p=0.002). Subgroup analysis of
      children of male cardiologists revealed higher incidence of male births with
      increasing age and radiation exposure and multivariate analysis only identified
      paternal age as predictor of higher incidence of male births (OR 1.05, CI 1.01
      1.089, p=0.0027). Conclusion: Exposure to ionizing radiation leads to a decrease
      in the sex ratio (M/F) in younger male cardiologists, while this effect is
      reversed with greater number of male births in older male cardiologists.

PMID- 28496835
TI  - Left Atrial Fibrosis: Role in Atrial Fibrillation Pathophysiology and Treatment
      Outcomes.
AB  - The mechanisms of atrial fibrillation are complex, and have been the subject of
      intensive study for over fifty years. There is likely a complex interplay between
      triggers and substrate that mediates the initiation and maintenance of AF.
      Increasingly, atrial fibrosis has been recognized as a key component of that
      substrate, playing a critical role in conduction abnormalities in the left atrium
      that appear necessary to maintaining AF. In the last several years, our abilities
      to quantify left atrial fibrosis - both through catheter- and MRI-based
      techniques - has shed important light on the underlying mechanisms of AF, and on
      therapeutic strategies to treat AF. Whether our increased appreciation of the
      role of atrial fibrosis in AF translates into improved efficacy of catheter
      ablation or anti-arrhythmic therapy, though, remains to be seen. The aim of this
      review is to summarize clinical investigations of atrial fibrosis as a factor in
      the development and treatment of atrial fibrillation.

PMID- 28496838
TI  - Why we Should Not Delay Ablation in New Onset Recurrent Atrial Fibrillation.
AB  - Recurrent episodes of atrial fibrillation are associated with progressive left
      atrial substrate remodelling over time. We present an argument for early ablation
      in the treatment of recurrent paroxysmal atrial fibrillation prior to such
      deleterious changes in "left atrial electrical health".

PMID- 28496837
TI  - Collateral Damage from Catheter Ablation of Atrial Fibrillation Lessons Learnt in
      the Past Decade.
AB  - Catheter ablation for atrial fibrillation (AF) has been increasingly performed
      over the past decade. Regardless of technological advances and technique
      improvement, catheter ablation for AF remains a highly complex procedure and the
      risk of procedural complications is not negligible. This article discusses the
      management and the approach to avoid the serious complications of catheter AF
      ablation including pulmonary vein stenosis, atrioesophageal fistula, cardiac
      tamponade, stroke and collateral nervous damage. The management of periprocedural
      anticoagulation and the complications associated with epicardial AF ablation are
      also described.

PMID- 28496840
TI  - Atrial Fibrillation Associated Costs for Stroke Hospitalizations of Medicare
      Beneficiaries in the Stroke Belt of the United States.
AB  - Purpose: To estimate atrial fibrillation (AF)-associated costs for stroke
      hospitalizations among Medicare beneficiaries aged >=65 years in a 11-state
      region called stroke belt in the United States. Methods: Using the 2010 Medicare
      Provider Analysis and Review File database, we analyzed costs of stroke
      hospitalizations, conditional on presence of AF (n=226 289) after excluding those
      with subarachnoid hemorrhage, no information on race, or a length of stay [LOS]
      of 30 or more days. We employed regression analysis to estimate for defined
      subgroups the impact of AF on costs while controlling for major potential
      confounders. Results: The average cost of all stroke hospitalizations was $27
      915. The presence of AF increased this cost by $2711 (9.4%; P<0.001). AF
      associated costs were $3159, $2610, and $2197 for patients aged 65-74, 75-84, and
      >=85 years, respectively (all P<0.001). Among hospitalization with a length of
      stay (LOS) of 14-29 days, AF increased the costs by $5888 (P<0.001). AF was not
      associated with higher costs for hospitalizations involving intracerebral
      hemorrhage. Conclusions: The costs of stroke hospitalizations are high, and they
      are even higher if the patient has AF. Further information is needed on the costs
      in patients with AF who are taking anticoagulants.

PMID- 28496839
TI  - Role of Stress in Cardiac Arrhythmias.
AB  - Stress is a major trigger of cardiac arrhythmias; it exerts profound effects on
      electrophysiology of the cardiomyocytes and the cardiac rhythm. Psychological and
      physiological stressors impact the cardiovascular system through the autonomic
      nervous system (ANS). While stressors vary, properties of the stress response at
      the level of cardiovascular system (collectively referred to as the autonomic
      cardiovascular responses) are similar and can be studied independently from the
      properties of specific stressors. Here, we will review the clinical and
      experimental evidence linking common stressors and atrial arrhythmias.
      Specifically, we will describe the impact of psychological and circadian
      stressors on ANS activity and arrhythmogenesis. We will also review studies
      examining relationships between autonomic cardiovascular responses and cardiac
      arrhythmias in ambulatory and laboratory settings.

PMID- 28496841
TI  - Three-Dimensional Transoesophageal Echocardiography in Electrophysiology
      Laboratory.
AB  - Percutaneous electrophysiological interventions such as atrial fibrillation and
      ventricular tachycardia ablation are usually monitored by fluoroscopy and
      electroanatomical mapping systems. Electroanatomical mapping systems lacks soft
      tissue contrast and adequate visualization of the target area such as right
      ventricular out-flow tract and left atrium. Recently, real-time 3D
      transoesophageal echocardiography (RT-3D TEE) has emerged as an important method
      for visualizing cardiac structures such as left atrium, left atrial appendix,
      interatrial septum, pulmonary veins, Marshall ligament and mitral valve annulus
      during invasive procedures. This review aims to describe the RT-3D TEE for the
      guidance of percutaneous interventional electrophysiological study especially at
      atrial fibrillation in the cardiac electrophysiology laboratory.

PMID- 28496842
TI  - Cerebral Embolization During AF Ablation -Pathophysiology, Prevention and
      Management.
AB  - Catheter based ablation therapy has evolved as an invaluable tool in the
      management of symptomatic patients with atrial fibrillation (AF). The procedure
      of AF ablation requires instrumentation in the systemic circulation predisposing
      to various concerns that can result in systemic embolization. We will describe
      the reported incidence of these events and refer to the various pathophysiologic
      explanations for their occurrence. Details on the risk factors and the relevant
      studies will also be reviewed. Preventive and treatment strategies in patients
      undergoing the ablation procedure will be discussed.

PMID- 28496843
TI  - Exploring the New Frontiers in the Left Atrial Appendage.

PMID- 28496844
TI  - Contrast Induced Thyrotoxicosis in a Patient with New onset Atrial Fibrillation:
      A Case Report and Review.
AB  - The development of thyrotoxicosis following the administration of iodinated
      contrast is a rare occurrence. The effect, referred to as the Jod-Basedow effect,
      is often observed in patients with underlying thyroid disease who develop
      thyrotoxicosis subsequent to the exposure of exogenous iodide. An example of an
      iatrogenic cause for this event may be seen when a large iodide load is given
      intravenously for studies or procedures. Thyrotoxicosis can also lead to cardiac
      arrhythmias including atrial fibrillation. This is a case presentation of a 74
      year old female who developed thyrotoxicosis as well as new onset atrial
      fibrillation approximately one week after receiving iodinated contrast dye for a
      diagnostic CT of the abdomen. We further review the prior published literature in
      regard to atrial fibrillation and thyrotoxicosis.

PMID- 28496845
TI  - Atrial Fibrillation Ablation in A Patient with Absent Pericardium.
AB  - A 45-year-old woman with drug-refractory paroxysmal atrial fibrillation (AF)
      underwent AF ablation. She had a history of abnormal chest radiograph, which on
      review was consistent with congenital absence of pericardium and this was later
      confirmed on cardiac magnetic resonance imaging. She had extreme leftward and
      posterior rotation of the heart, resulting in abnormal fluoroscopic appearance of
      the electrophysiological catheters and orientation of the interatrial septum.
      This along with exaggerated beat to beat motion of the heart posed significant
      technical challenges for the electrophysiologist during left atrial access and
      pulmonary vein isolation.

PMID- 28496846
TI  - Role of Cardiac Imaging for Catheter-based Left Atrial Appendage Closure.
AB  - Thromboembolic stroke is the most serious complication in patients suffering from
      Atrial Fibrillation. Atrial thrombi have a predilection to form in the left
      atrial appendage. Accordingly, oral anticoagulation is recommended for patients
      with high risk of stroke. However, it is widely underused and problems of
      compliance are associated with serious risk of bleeding or inefficacy. In these
      patients with non-valvular atrial fibrillation, percutaneous occlusion of the
      left atrial appendage might help to reduce the risk of thromboembolism. Cardiac
      imaging plays a crucial role at all stages of this procedure and trans-esophageal
      echocardiography represents the current gold-standard for the assessment of the
      left atrial appendage. Cardiac imaging is mandatory to precisely determine the
      left atrial appendage anatomy and to select the appropriate size for the device.
      Finally, real time three-dimension echocardiography is a powerful additional tool
      that improves the safety profile of the procedure. 3D-transoesophageal
      echocardiography allows for the accurate assessment of left atrial appendage
      anatomy and helps determine if it's suitable for device implantation. Finally, it
      also allows for continuous visualization of all intracardiac devices and
      catheters during the procedure, and the clear delineation of device positioning
      in the left atrial appendage.

PMID- 28496847
TI  - CHADS2 and CHA2DS2Vasc-Score in Peripheral Systemic Embolism.
AB  - Objectives: We analysed the characteristics of patients with an acute peripheral
      embolic event considering the possible use of the CHADS2-Score and the
      CHA2DS2Vasc-Score Patients and Methods: We retrospectively analyzed 163 cases of
      acute peripheral arterial embolism treated in the Department of Vascular Medicine
      of the HELIOS Klinik Krefeld, Germany, from 2008 to 2011. We retrospectively
      screened the medical form for information regarding atrail fibrillation (AF) and
      the risk factors necessary to calculate the CHADS2 and CHA2DS2vasc score.
      Results: Arterial hypertension and age > 75 years were the most frequent risk
      factors. Mean CHADS2 score was similar in males and females (2.3 +/- 1.5 and 2.3
      +/- 1.4). 66% of the males and 63.3% of the females scored 2 and more points.
      Mean CHA2DS2Vasc score was 3.6 +/- 2.0 in males and 4.6 +/- 1.9 in females. 85.2%
      of the males and 95.4% of the females scored more than 2 points. In the medical
      forms AF was documented in 79 (48%) patients, of which 23 (43 %) were males and
      56 (51%) females. Mean CHADS2 score and mean CHA2DS2Vasc score were slightly
      higher in those with AF compared to the total group, but not significantly
      different. The rate of patients with 2 and more points increased for both scores:
      CHADS2 score: males 82.6% and females 76.8%, CHA2DS2Vasc: males 100% and females
      98.2%. Almost half of the patients with AF had had anticoagulation with
      phenprocoumon before (males 12 (52%), females 24 (43%), but only every 10th was
      within the therapeutic range (INR >=2) Conclusion: The number of those with AF is
      high amongst patients with acute peripheral embolism. According to the CHADS2 and
      CHA2DS2Vasc score, most of these patients had an indication for oral
      anticoagulation independent form the embolic event.

PMID- 28496848
TI  - Surgery for Atrial Fibrillation: Selecting the Procedure for the Patient.
AB  - This manuscript aims to review the current knowledge in the field of surgical
      ablation of atrial fibrillation (AF), including a brief discussion regarding the
      standard Maze procedure, its variants, minimally invasive thoracoscopic
      procedures and hybrid treatments, which briefly summarizes the advantages and
      differences between each technique. The rationale for the surgical approach of
      the left atrial appendage, its different techniques and complications will also
      be briefly covered. To conclude, the current Expert Consensus recommendations
      will be reviewed and an algorithm for the surgical management of the patient with
      AF, suggesting which technique applies better to which patient, under specific
      settings, will also be proposed.

PMID- 28496851
TI  - Age as a Risk Factor for Stroke in Atrial Fibrillation Patients: Implications in
      Thromboprophylaxis in the Era of Novel Oral Anticoagulants.
AB  - Atrial fibrillation is associated with significant morbidity and mortality. There
      is a strong relationship between atrial fibrillation and aging, thromboembolism,
      stroke, congestive heart failure and hypertension. In addition, advanced age is a
      powerful risk factor for stroke and thromboembolism in patients with atrial
      fibrillation. For many years, vitamin K antagonists were the only approved
      anticoagulants for the management of atrial fibrillation. Lately new
      anticoagulants made their appearance and large trials have already shown their
      superiority against vitamin K antagonists. Since the arrhythmia is encountered
      frequently in the elderly, it is crucial to identify the beneficial effects of
      the novel oral anticoagulants in this particular patient population.

PMID- 28496849
TI  - Atrial Fibrillation and Heart Failure: A Review of the Intersection of Two
      Cardiac Epidemics.
AB  - Atrial fibrillation and heart failure are closely linked cardiac conditions that
      are both increasing in prevalence due to shared risk factors and common disease
      mechanisms. The presence of both disease entities portends an increase in
      morbidity and mortality. There are significant similarities in the treatment
      strategies of these conditions, and the adequate management of one disease may
      prevent the development of the other. To this date, a rhythm control strategy,
      even in the heart failure population, has not been proven to be superior to a
      rate control strategy. This may in large be due to study design coupled with
      deleterious effects of antiarrhythmic agents. There have been considerable
      advances over the past decade in catheter and device based management of atrial
      fibrillation and studies aimed to examine their long-term effect in patients with
      heart failure are underway.

PMID- 28496850
TI  - Hybrid Therapy for Atrial Fibrillation: where the Knife meets the Catheter.
AB  - During the past decades there has been a consistent evolution of both surgical
      and catheter-based techniques for the treatment of stand-alone atrial
      fibrillation, as alternatives or in combination with anti-arrhythmic drugs.
      Transcatheter ablation has significantly improved outcomes, despite often
      requiring multiple procedures and with limited success rates especially in
      presence of persistent atrial fibrillation. Surgical procedures have dramatically
      evolved from the original cut-and-sew Maze operation, allowing nowadays for
      closed-chest epicardial ablations on the beating heart. Recently, the concept of
      a close collaboration between the cardiac surgeon and the electrophysiologist has
      emerged as an intriguing option in order to overcome the drawbacks and suboptimal
      results of both techniques; therefore, the hybrid approach has been proposed as a
      potentially more successful strategy, allowing for a patient-tailored
      therapeutical approach. We reviewed the recent advancements either from the
      transcatheter and surgical standpoint, with a peculiar focus on the current
      option to merge both techniques along with an up-to-date review of the
      preliminary clinical experiences with the hybrid, surgical-transcatheter
      treatment of stand-alone atrial fibrillation.

PMID- 28496852
TI  - Rate Control in Atrial Fibrillation: Methods for Assessment, Targets for
      Ventricular Rate during AF, and Clinical Relevance for Device Therapy.
AB  - Rate control is a widely used treatment strategy for management of patients with
      atrial fibrillation (AF). Multiple studies have shown that pharmacologic rate
      control is as effective as pharmacologic rhythm control for management of AF. A
      snapshot ECG or intermittent monitoring using Holters is the most widely used
      technique for assessing ventricular rate during AF. Patients with implantable
      devices, such as pacemakers, implantable cardioverter defibrillators, cardiac
      resynchronization therapy devices, and implantable loop recorders provide the
      ability for continuous long term monitoring of AF and ventricular rate during AF.
      It has been shown that continuous monitoring of AF and ventricular rate during AF
      by implantable devices is the most comprehensive method for assessment of AF
      occurrence and poor rate control, particularly in patients with paroxysmal and
      asymptomatic AF. Rapid ventricular rate during AF, as assessed by implantable
      devices, has been shown to cause reduction in cardiac resynchronization therapy,
      predict inappropriate defibrillation therapy, and identify increased risk for
      cardiovascular hospitalizations. The ventricular rate targets for achieving good
      rate control during AF depend on the patient characteristics with stricter
      targets recommended for patient with compromised functional capacity, such as
      patients with HF. Thus it can be hypothesized that timely intervention based on
      continuous assessment of AF and poor rate control, with ventricular rate targets
      defined based on cardiovascular disease state, may improve clinical outcomes in
      patients with AF.

PMID- 28496853
TI  - Thinking outside the Box: Rotor Modulation in the Treatment of Atrial
      Fibrillation.
AB  - Ablation for atrial fibrillation (AF) is an important and exciting therapy whose
      results remain suboptimal. Although most clinical trials show that ablation
      eliminates AF more effectively than medications, it is disappointing that the
      continued single procedural success remains ~50% despite the substantial advances
      that have taken place in imaging, catheter positioning and energy delivery. Focal
      impulse and rotor modulation (FIRM), on the other hand, offers the opportunity to
      precisely define and then ablate patient-specific sustaining mechanisms for AF,
      rather than trying to eliminate all possible AF triggers. For over a decade,
      electrophysiologists have described cases in which AF terminates after only
      limited ablation - usually that cannot be explained by 'random' meandering
      wavelets. Indeed, recent studies from several laboratories show that all forms of
      clinical AF are typically 'driven' by stable electrical rotors and focal sources,
      not by multiple meandering waves. FIRM mapping enables an operator to place a
      catheter at typically 1-3 predicted sites in the atria, and with <5-10 minutes of
      RF ablation, terminate AF and potentially render it non-inducible. Several
      independent laboratories have now shown that such FIRM ablation alone can
      terminate or substantially slow AF in >80% of patients with persistent and
      paroxysmal AF and increase the single procedure rate of AF elimination from 50%
      with PV isolation alone to >80%. Ongoing studies hint that FIRM only ablation,
      enabling ablation times in the range observed for typical atrial flutter, may
      also achieve these high success rates without subsequent trigger ablation. This
      review summarizes the current state-of-the-art on FIRM mapping and ablation.

PMID- 28496854
TI  - Sleep Disordered Breathing and the Pathogenesis of Atrial Fibrillation.
AB  - This review illustrates the importance of sleep disordered breathing in evolution
      and progression of atrial fibrillation. While in early years associations were
      mainly attributed to the impact of hypoxemia and hypertension, nowadays multiple,
      additional pathways have been investigated or are currently under investigation.
      Sleep disordered breathing has been shown to have a direct impact on mechanical
      and electrical remodeling. In addition hypercapnia and negative intrathoracic
      pressure seem to alter atrial electrophysiology. Finally, impacts on inflammation
      and metabolic dysregulation display the complex interplay between breathing
      disorders and evolution and progression of atrial fibrillation.

PMID- 28496855
TI  - Pharmacological Therapy in Stroke Prophylaxis - The New versus the Old Agents.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in
      clinical practice. AF is a potent risk factor for stroke and systemic
      thromboembolism. Patients with AF have been observed to have a worse outcome
      following stroke, therefore prevention of stroke in patients with AF is of
      paramount importance. Antithrombotic therapy is crucial for prevention of stroke
      in patients with AF. Vitamin K antagonists (VKAs) have been the traditional
      anticoagulants for prevention of stroke in patients with AF. Drug treatment with
      VKAs is associated with significant management issues, such as an unpredictable
      dose response necessitating dose adjustments, frequent laboratory monitoring and
      multiple interactions with other drugs. Despite following best practices, VKAs
      are associated with limited efficacy and increased risk of hemorrhage. Due to
      these limitations a significant effort has been devoted towards development of
      newer anticoagulants. Dabigatran, Rivaroxaban, and more recently Apixaban have
      been approved by the F.D.A. for the prevention of stroke in patients with AF.
      These newer agents possess highly predictable pharmacokinetic and
      pharmacodynamics properties which allow a fixed dosing regimen and also eliminate
      the need of routine laboratory monitoring. This review discusses various
      anticoagulants for prevention of stroke in patients with AF.

PMID- 28496856
TI  - Do Omega-3 Fatty Acids Decrease the Incidence of Atrial Fibrillation?
AB  - Although atrial fibrillation is a very common medical problem in general
      population and has a high incidence in the setting of open heart surgery, there
      are very few therapies to prevent occurrence or recurrence of atrial
      fibrillation. N-3 polyunsaturated fatty acids have been shown to change basic
      physiologic properties of the atrial tissue to make it less susceptible to atrial
      fibrillation. In this review, we first describe basic physiological mechanisms
      thought to be responsible for these changes and then discuss observational and
      interventional studies evaluating the use n-3 polyunsaturated fatty acids for
      primary and secondary prevention of atrial fibrillation in the general
      population, in subjects undergoing open heart surgery, and in special subgroups
      of patients.

PMID- 28496857
TI  - Catheter Ablation of Atrial Fibrillation in Patients with Hardware in the Heart -
      Septal Closure Devices, Mechanical Valves and More.
AB  - Patients with mechanical "hardware" in the heart, such as those with mechanical
      cardiac valves or atrial septal closure devices, represent a population at high
      risk of developing AF. Catheter ablation of AF in these subjects might represent
      a challenge, due to the perceived higher risk of complications associated with
      the presence of intracardiac mechanical devices. Accordingly, such patients were
      excluded or poorly represented in major trials proving the benefit of catheter
      ablation for the rhythm-control of AF. However, recent evidence supports the
      concept that catheter ablation procedures might be equally effective in these
      patients, without a significant increase in the risk of procedural complications.
      This review will summarize the current state-of-the-art on catheter ablation of
      AF in patients with mechanical "hardware" in the heart.

PMID- 28496858
TI  - Comparing Antiarrhythmic Drugs and Catheter Ablation for Treatment of Atrial
      Fibrillation.
AB  - In the past years, catheter ablation has evolved into an effective treatment
      option for symptomatic, drug-resistant atrial fibrillation (AF) and it has
      recently been implemented as a primary treatment strategy for patients with
      paroxysmal AF. Although a significant number of studies have evaluated the
      potential benefits of catheter ablation compared with anti-arrhythmic drug (AAD)
      therapy, to date, there are only a small number of randomised controlled trials
      in the literature, and several issues remain unsolved. The aim of this review is
      to analyze the current literature regarding this important issue and further
      discuss the question, whether catheter ablation may be more beneficial when
      compared to AAD therapy.

PMID- 28496860
TI  - Left Atrial Appendage Thrombus Despite Anticoagulation.
AB  - The American College of Cardiology Foundation/American Heart Association task
      force on practice guidelines recommend therapeutic anticoagulation for at least 3
      weeks prior to cardioversion in patients with atrial fibrillation of 48-hour
      duration or longer, or when the duration of atrial fibrillation is unknown. This
      case report demonstrates the presence of thrombi in the left atrial appendage
      despite adequate anticoagulation, challenging the current guidelines. Therapeutic
      anticoagulation for at least 3 weeks followed by transesophageal echocardiography
      in search of thrombus may enhance thromboembolic safety of elective
      cardioversion. Atrial fibrillation (AF) and heart failure (HF) have emerged as
      major cardiovascular epidemics in developed nations over the past decade. They
      share similar risk factors, seem to mutually accelerate progression and are
      associated with increased morbidity and mortality. Their relationship involves
      complex hemodynamic, neuro-hormonal, inflammatory and electrophysiologic
      mechanisms, which go beyond just mutual risk factors. This review focuses on
      updates in AF and HF with a hope of better understanding this relationship and
      the management of this complex duo.

PMID- 28496859
TI  - Anti-Arrhythmic Agents in the Treatment of Atrial Fibrillation.
AB  - Although atrial fibrillation (AF) is the most common sustained arrhythmia seen
      during daily cardiovascular physician practice, its management remained a
      challenge for cardiology physician as there was no single anti-arrhythmic agents
      proved to be effective in converting atrial fibrillation and kept its
      effectiveness in maintaining sinus rhythm over long term. Moreover all the anti
      arrhythmic agents that are used in treatment of AF were potentially pro
      arrhythmic especially in patients with coronary artery disease and structurally
      abnormal heart. Some of these drugs also have serious non cardiac side effects
      that limit its long term use in the management of atrial fibrillation. Several
      new and investigational anti-arrhythmic agents are emerging but data supporting
      their effectiveness and safety are still limited. In this systematic review we
      examine the efficacy and safety of these medications supported by the major
      published randomized trials, meta-analyses and review articles and conclude with
      a summary of guidelines recommendations.

PMID- 28496861
TI  - Cardiac Remodeling After Atrial Fibrillation Ablation.
AB  - Radiofrequency catheter ablation procedures are considered a reasonable option
      for patients with symptomatic, drug refractory atrial fibrillation (AF). Ablation
      procedures have been reported to effectively restore sinus rhythm and provide
      long-term relief of symptoms. Both electrical and structural remodeling occurs
      with AF. A reversal of the electrical remodeling develops within 1 week after
      restoration to sinus rhythm following the catheter ablation. The recovery rate is
      faster in the right atrium than the left atrium. Reverse structural remodeling
      takes longer and is still present 2 to 4 months after restoration of sinus
      rhythm. The left atrial transport function also improves after successful
      catheter ablation of AF. Left atrial strain surveys from echocardiography are
      able to identify patients who respond to catheter ablation with significant
      reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic
      resonance imaging is also able to determine the degree of atrial fibrosis and is
      another tool to predict the reverse remodeling after ablation. The remodeling
      process is complex if recurrence develops after ablation. Recent evidence shows
      that a combined reverse electrical and structural remodeling occurs after
      ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical
      remodeling without any structural remodeling develops in those with recurrence
      involving chronic AF. Whether progressive atrial remodeling is the cause or
      consequence during the recurrence of AF remains obscure and requires further
      study.

PMID- 28496862
TI  - Cost-Effectiveness of Atrial Fibrillation Ablation.
AB  - Atrial fibrillation (AF) is a frequently encountered rhythm disorder,
      characterized by high recurrence rate, frequent hospitalizations, reduced quality
      of-life and increased the risk of mortality, heart failure and stroke. Along with
      these clinical complications this type of arrhythmia is the major driver of
      health-related expenditures. Radiofrequency catheter ablation (RFA) of atrial
      fibrillation has been shown to improve freedom from arrhythmia survival, reduce
      re-hospitalization rate and provide better quality-of-life as compared with rate
      control and rhythm control with antiarrhythmic therapy. Efficacy of AF ablation
      in terms of outcomes and costs has an evolving importance. In this review, we
      aimed to highlight current knowledge on AF ablation clinical outcomes based on
      results of randomized clinical trials and community-based studies, and overview
      how this improvement in clinical end-points affects costs for arrhythmia care and
      cost-effectiveness of AF ablation.

PMID- 28496863
TI  - Effect of Age on Outcomes of Catheter Ablation of Atrial Fibrillation.
AB  - Age has a great impact in the development of atrial fibrillation, which is the
      most common arrhythmia found in the elderly. The higher risk of stroke, heart
      failure and mortality associated with atrial fibrillation highlights the need for
      successful therapeutic interventions that can translate in better outcomes in
      this population. The introduction of catheter ablation has revolutionized the
      management of atrial fibrillation over the past decades with an undeniable impact
      in morbidity, mortality and quality of life. This benefit has not been fully
      extended to the older patients due to the lack of definitive data from randomized
      control trials assessing the impact ofrhythm control strategies such as catheter
      ablation in this population, in whom a rate-control strategy has been suggested
      as a better therapeutic option. In this review, we summarize the pathogenesis of
      atrial fibrillation in the elderly, the benefits and complications of catheter
      ablation reported in the literature and the impact of age in the outcomes of
      ablation compared to younger populations.

PMID- 28496865
TI  - Building Atrial Fibrillation Awareness: Is it Time to get Beyond the Top Line?
AB  - Public awareness of atrial fibrillation and its consequences is increasing. In
      the current environment, this is driven largely by promotion of individual
      therapies. This editorial discusses the need for greater depth in the discussion
      of the disease state, its progression and economic consequences as well as the
      risk of death and disability. The adverse effects of therapies on cardiovascular
      outcomes is a major need in public education. New initiatives should address
      these important new insights and needs.

PMID- 28496864
TI  - Catheter Ablation of Atrial Fibrillation in Females.
AB  - Catheter ablation for the management of atrial fibrillation (AF) has evolved as a
      successful therapy widely used. Women with AF show a higher risk for AF-related
      morbidity due to stroke, a poorer tolerance to antiarrhythmic pharmacological
      therapy and a weaker quality of life; for this reason a curative, catheter-based
      approach for AF appears very attractive in women. Reported details on female AF
      population undergoing catheter ablation, as well as success and complication
      rates will be reviewed.

PMID- 28496866
TI  - Atrial Fibrillation after Radiofrequency Ablation of Type I Atrial Flutter.
AB  - Typical atrial flutter (AFL) or type I AFL is the most common type of
      macroreentrant atrial tachycardia. Its prevalence increases with age and is more
      common in men. Ablation of the cavo-tricuspid isthmus (CTI), a critical part of
      the circuit, is safe and highly effective. Despite the long-term efficacy of this
      therapy, a significant proportion of patients undergoing CTI ablation will
      develop atrial fibrillation (AF) during the follow-up and identifying them can
      have an important impact on their management. PV isolation and typical flutter
      ablation during the same procedure may be an effective treatment strategy for
      patients with clinical documentation of both arrhythmias.

PMID- 28496868
TI  - Automated Detection of Complex Fractionated Atrial Electrograms In Substrate
      Based Atrial Fibrillation Ablation: Better Discrimination with a New Setting of
      CARTO(r) Algorithm.
AB  - Background and purpose: Up until recently complex fractionated atrial electrogram
      (CFAE) ablation has been considered as time consuming and its achievement as
      challenging, especially for non experimented operators. Moreover, results of
      substrate ablation based on CFAE detection in atrial fibrillation (AF) are very
      disparate, mainly because of the operator's subjective electrogram visual
      analysis and the difficult distinction between CFAEs really involved in AF
      perpetuation from other CFAE. Automatic detection provided by 3D mapping system
      (CARTO(r) algorithm) can be helpful but is not selective enough, drawing too wide
      CFAE areas. We sought to demonstrate a better selectivity of a new CFAE algorithm
      setting in order to better discriminate CFAEs really involved in AF perpetuation
      from other CFAE. Methods and subjects: A population of 32 patients (60.4+/-12.7
      years) with paroxysmal (n=3) AF (PAF), persistent (n=16) AF (PeAF) or long
      standing persistent (n=13) AF (LSPeAF), and AF history =56+/-65 months, underwent
      CFAE ablation based on visual analysis. Before ablation, left atrium CFAE mapping
      was performed on CARTO(r) shortest complex interval (SCI) algorithm and
      reanalyzed after ablation with the two different settings: nominal (SCI 60
      120ms/0.05-0.15mV) vs. customized setting (SCI 30-40ms/0,04-0.15mV). CFAE areas
      automatically detected by both settings (CFAE-CARTO(r) areas) were respectively
      measured. The decision to ablate CFAE was only based upon the operator's
      electrogram visual analysis taken as reference because of high AF termination
      rate (93.7%) due to operator's CFAE selection experience. These ablation points
      drawn reference-CFAE areas involved in AF perpetuation (ablation point=60mm2)
      allowing to compare the selectivity of the two previous automatic maps. Results:
      With the customized CARTO(r) SCI setting, we observed a significant reduction of
      CFAE areas detected by CARTO(r) (CFAE-CARTO(r) areas) and of the ablated CFAE
      surface inside non-CFAE CARTO(r) areas, (30.6+/-20.5cm2 vs. 68.8+/-24.5cm2,
      p<0.0001, and 1.86+/-1.82% vs. 3+/-3%, p=0.003). Furthermore the proportion of
      ablated areas/detected CFAE-CARTO(r) areas were higher with customized setting
      (38.2+/-19.6% vs. 20.4+/-17.5%, p=0.008). Conclusions: This new customized CFAE
      algorithm setting is significantly more selective than the nominal one and allows
      an automated detection of CFAE really involved in AF perpetuation truer to an
      efficient experienced operator's electrogram visual analysis.

PMID- 28496867
TI  - Atrial Fibrillation - A Common Ground for Neurology and Cardiology.
AB  - Atrial fibrillation (AF) has a huge impact on clinical stroke because it is the
      primary cause of cardio-embolism, which constitutes ~20% of all strokes. As a
      result, there is a great need to explore safer and more effective primary and
      secondary prophylactic agents. In this article, we discuss the overlapping issues
      pertaining to AF from both a neurology and cardiology standpoint. We focus on the
      dynamic interplay of neurovascular and cardiovascular diseases in relation to AF,
      traditional and novel risk factors for AF leading to stroke, impact of AF on
      cognitive decline, and current upstream medical and surgical options for embolism
      prophylaxis.

PMID- 28496870
TI  - Differences In Tissue Injury and Ablation Outcomes In Atrial Fibrillation
      Patients - Manual versus Robotic Catheters.
AB  - Robots have gained their place in almost all areas of our daily life. Robotic
      systems have been introduced for ablation therapies associated with the hope of
      automation of procedures, increase in precision of lesion placement, improved
      energy transmission to the tissue and reduction in radiation exposure of the
      patients and the interventionalist. Finally, they may be associated with higher
      comfort for the operator by transferring his work into the control room and
      thereby supersede wearing sterile and radiation protective clothing. Systems
      providing a remote mechanical replacement of the operators' hands have been
      introduced as well as systems guiding the catheter tip by external magnets.
      Guiding of the catheter tip has major impact on contact to the tissue and thereby
      modifies energy transmission. This may be advantageous in terms of higher
      catheter stability and modification of contact towards a more constant than
      intermittent type of contact. However, increasing contact bears the risk of
      mechanical perforation and excessive energy delivery. Many clinical studies have
      been conducted evaluating novel remotely guiding techniques in atrial
      fibrillation ablation procedures. Although only a few of them are prospectively
      randomized, reduction in fluoroscopy exposure has been found in most of the
      trials. Data on outcome is less uniform. It seems that remote navigation does not
      improve outcomes and on the other hand does not increase complication rates.
      However, large prospectively randomized trials conducted by operators well
      skilled not only in manual but also in remote techniques would be needed to
      compare outcomes particularly in terms of decrease in complication rates.
      Finally, the type of navigation chosen actually is and probably will remain a
      question of personal preference.

PMID- 28496869
TI  - Treatment Considerations for a Dual Epidemic of Atrial Fibrillation and Heart
      Failure.
AB  - Atrial fibrillation (AF) and heart failure (HF) have emerged as major
      cardiovascular epidemics in developed nations over the past decade. They share
      similar risk factors, seem to mutually accelerate progression and are associated
      with increased morbidity and mortality. Their relationship involves complex
      hemodynamic, neuro-hormonal, inflammatory and electrophysiologic mechanisms,
      which go beyond just mutual risk factors. This review focuses on updates in AF
      and HF with a hope of better understanding this relationship and the management
      of this complex duo.

PMID- 28496871
TI  - Silent Cerebral Embolism during Atrial Fibrillation Ablation:Pathophysiology,
      Prevention and Management.
AB  - Although many efforts have been directed to improve atrial fibrillation
      transcatheter ablation safety, thromboembolism to the brain remains one of the
      major complications. In fact several studies have confirmed occurrence of silent
      cerebral embolic lesions by post-procedure magnetic resonance imaging. The
      present review will focus on the possible mechanisms leading to silent cerebral
      embolism in an attempt to provide recommendations holding the potential to reduce
      the incidence of this clinically relevant complication.

PMID- 28496872
TI  - Atrial Fibrillation and Renal Disease.
AB  - Co-incidence of atrial fibrillation and renal dysfunction in general population
      is described in many epidemiological studies. Major issue is optimal
      anticoagulation in patients with atrial fibrillation and renal disease warranting
      balance between risks of ischemic stroke and hemorrhages. The second issue is
      catheter ablation of AF patients with renal dysfunction. Both issues are
      discussed in this paper.

PMID- 28496873
TI  - Connexin Remodeling Contributes to Atrial Fibrillation.
AB  - Atrial fibrillation significantly contributes to mortality and morbidity through
      increased risk of stroke, heart failure and myocardial infarction. Investigations
      of mechanisms responsible for the development and maintenance of atrial
      fibrillation have highlighted the importance of gap junctional remodeling.
      Connexins 40 and 43, the major atrial gap junctional proteins, undergo
      considerable alterations in expression and localization in atrial fibrillation,
      creating an environment conducive to sustained reentry. Atrial fibrillation is
      initiated and/or maintained in this reentrant substrate. This review will focus
      on connexin remodeling in the context of underlying mechanism and possible
      therapeutic target for atrial fibrillation.

PMID- 28496874
TI  - The Progressive Nature of Atrial Fibrillation:A Rationale for Early Restoration
      and Maintenance of Sinus Rhythm.
AB  - Atrial fibrillation (AF) is the manifest outcome of a multifactorial, progressive
      disease process,secondarily or primarily involving the atrial chambers. The
      slowly progressive electrostructural alterations diffusely involve the atrial
      substrate and lead to persistent and permanent forms of AF. Although the
      progression of the AF disease process is variable and associated with the
      development of comorbid conditions, rhythm restoration therapies, particularly
      catheter ablation,provide higher acute and long-term success rates in paroxysmal
      than non-paroxysmal AF. This review of literature aims to discuss how early
      restoration and maintenance of sinus rhythm especially using novel approaches can
      influence the progressive nature of atrial fibrillation.

PMID- 28496875
TI  - Hybrid Therapy for Atrial Fibrillation - Optimizing Treatment Strategies.
AB  - Endocardial atrial fibrillation (AF) ablation techniques enable one to
      characterize the underlying substrate in order to tailor the ablation procedure
      but these ablation lesions are not always transmural nor long lasting. Surgical
      AF ablation techniques, on the other hand, create reliable linear lesions but the
      lesion set is based on empirical assumptions rather than specific patient
      characteristics. Performed in combination, both approaches seem to be
      complementary as they overcome their mutual shortcomings. Several hybrid or
      convergent ablation strategies with the use of various energy sources have been
      described. Medium and long term results are encouraging, especially in
      challenging settings such as persistent AF and failed endocardial catheter
      ablations.

PMID- 28496876
TI  - Diabetes, Obesity and Atrial Fibrillation: Epidemiology, Mechanisms and
      Interventions.
AB  - Body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM)
      and cardiovascular (CV) morbidity and mortality. Over the last few decades, we
      have witnessed a global rise in adult obesity of epidemic proportions. Similarly,
      there has been a parallel increase in the incidence of atrial fibrillation (AF),
      itself a significant cause of cardiovascular morbidity and mortality. This may be
      partly attributable to advances in the treatment of coronary heart disease (CHD)
      and heart failure (HF) improving life expectancy, however, epidemiological
      studies have demonstrated an independent association between obesity, diabetes
      and AF, suggesting possible common pathophysiological mechanisms and risk
      factors. Indeed, cardiac remodeling, haemodynamic alterations, autonomic
      dysfunction, and diastolic dysfunction have been reported in obese and diabetic
      cohorts. Moreover, diabetic cardiomyopathy is characterized by an adverse
      structural and functional cardiac phenotype, which may predispose to the
      development of AF. In this review, we discuss the pathophysiological and
      mechanistic relationships between obesity, diabetes and AF, and some of the
      challenges posed in the management of this high-risk group of individuals.

PMID- 28496878
TI  - High Incidence of Atrial Fibrillation or Flutter in Stroke Patients Who Have the
      Clinical Risk Factors for Stroke.
AB  - The incidence of stroke in patients with atrial fibrillation or flutter (AF) is
      well known and depends on the presence of risk factors. The incidence of AF in
      patients who have a stroke and its relationship to risk factors is not as clear,
      however, because many stroke patients may have occult intermittent AF that is not
      present at the time of stroke and is not diagnosed. To better assess the
      incidence of AF, we studied the clinical records and all the 12 lead ECGs in a 14
      year medical center data base of 985 patients admitted with ischemic stroke over
      a 3 year period and correlated the incidence of AF with the presence of the
      stroke risk factors. Of the stroke patients with congestive heart failure 61.9%
      had AF (95%CL 54.4, 68.9), with age >/=75 years 45.2% had AF(CL 41.0,49.4), with
      coronary artery disease 42.9% had AF (CL 36.8,49.2), with diabetes 39.2% had AF
      (CL 32.8,46.1) and with hypertension 33.7 % had AF(CL 30.5,37.1) , all
      significantly higher than without these risk factors. Patients with > 1 risk
      factor or with echo abnormalities, especially left atrial enlargement, had an
      even higher incidence of AF. These findings suggest that AF may be a very common
      mechanism whereby the stroke risk factors cause stroke. Stroke patients in normal
      sinus rhythm with these risk factors should be monitored for AF so they can
      receive anticoagulation to prevent a subsequent stroke if AF is diagnosed.

PMID- 28496877
TI  - Homogenization of Atrial Electrical Activities: Conceptual Restoration of
      Regional Electrophysiological Parameters to Deter Ischemia-Dependent
      Conflictogenic Atrial Fibrillation.
AB  - Atrial fibrillation (AF) as a severe arrhythmia is now spreading worldwide at
      overwhelmingly high rates, particularly in elderly patients. Despite new
      insights, the mechanisms underlying AF are not conclusively determined yet.
      Taking into account the ischemic origin of arrhythmia induction (according to the
      so-called conflictogenic atrial fibrillation, declared recently) restoration of
      regional electrophysiological parameters is essential in tackling AF. We
      hypothesized that some atrial electrophysiological parameters, preferably the
      effective refractory period, might need to be controlled to prevent AF. All the
      remaining parameters - conduction velocity, conduction time, recovery time,
      vulnerability, excitability, repolarization etc. being as if secondary and less
      important could be ignored. Homogenization of the milieu producing AF might be
      implemented, at least theoretically, through restoration of blood supply in
      ischemic areas and/or via attenuation of electrophysiological differences between
      conflicting regions by delivery of atrial sub-threshold non-captured pulse
      trains. Adjunctive therapy by drugs containing vasodilatory features and
      affecting the effective refractory period appears to be fundamental. Thus,
      stabilization of disorganized atrial cellular activities likely may lead to the
      recovery of atrial excitable characteristics. Despite the lack of compelling
      evidence, the application of the concept may be helpful in order to search for
      more precise and more effective methods to favorably change the refractory
      period. Further studies are necessary to determine whether restoration or
      improvement of blood circulation of atrial wall is feasible. Based on such
      considerations a novel preventive AF strategies are to be designed.

PMID- 28496879
TI  - The Role of the Atrial Neural Network In Atrial Fibrillation: The Metastatic
      Progression Hypothesis.
AB  - With the advent of catheter ablation of atrial fibrillation (AF) there has been
      acceleration in our understanding of the mechanisms underlying the etiology of
      this common clinical arrhythmia. In this regard, the role of the intrinsic
      cardiac autonomic nervous system in the initiation and maintenance of AF began to
      receive attention in numerous experimental and clinical investigations. Up to
      now, the focus has been on the large ganglionated plexi (GP) which are located in
      the posterior left atrium mainly at the pulmonary vein-atrial junctions. As long
      term outcomes have been reported and single procedures have indicated diminished
      success rates particularly for persistent/long standing persistent AF, emphasis
      has begun to shift away from the pulmonary vein isolation (PVI) alone as well as
      GP ablation with or without PVI. An understanding of the atrial substrate
      represented by the extensions of the intrinsic cardiac autonomic system
      constituting the atrial neural network is beginning to evolve. In this review,
      the contribution of the intrinsic cardiac autonomic nervous system to the
      etiology of AF is addressed, particularly in regard to the greater prevalence of
      AF in the elderly. In addition, we emphasize the involvement of the atrial neural
      network in the "metastatic" progression of paroxysmal to persistent and long
      standing persistent forms of AF.

PMID- 28496880
TI  - Left Atrial Thrombosis Despite Dabigatran Therapy.
AB  - Dabigatran is a novel anticoagulation which has been approved as an alternative
      to warfarin therapy for non-valvular atrial fibrillation. Use of Dabigatran for
      approved indications as well as off label use has dramatically increased after
      Federal Drug Administration (FDA) approval. Our patient had left atrial
      thrombosis even after being on Dabigatran for more than one month which raises
      question about safety and efficacy of use of dabigatran around cardioversion and
      ablation.

PMID- 28496881
TI  - Hiatal Hernia Is Associated With an Increased Prevalence of Atrial Fibrillation
      in Young Patients.
AB  - Purpose: Hiatal hernia (HH) causes protrusion of the stomach into the chest
      cavity, directly impinging on the left atrium and possibly increasing
      predisposition to atrial arrhythmogenesis. However, such association has not been
      fully explored. The objective was to determine if an association between HH and
      atrial fibrillation (AF) exists and whether there are age- and sex-related
      differences. Methods: Adult patients diagnosed with HH from 1976 to 2006 at Mayo
      Clinic Rochester, Minnesota, were evaluated for AF. The number of patients with
      AF and HH was compared to age- and sex-matched patients with AF reported in the
      general population. Long-term outcomes were compared to corresponding county and
      state populations. Results: During the 30-year period, 111,429 patients were
      diagnosed with HH (mean age 61.4 +/- 13.8 years, 47.9% male) and 7,865 patients
      (7.1%) also had a diagnosis of AF (mean age 73.1 +/- 10.5 years; 55% male). In
      younger patients (<55 years), the occurrence of AF was 17.5-fold higher in men
      with HH and 19-fold higher in women with HH compared to the frequency of AF
      reported in the general population. Incidence of heart failure for patients with
      AF and HH was worse compared to the overall county population, but better than
      for those with AF. Similarly, mortality was worse in patients with AF and HH
      compared to the overall state population, but better than for those with AF in
      the county. Conclusion: Hiatal hernia appears to be associated with increased
      frequency of AF in both men and women of all age groups, but particularly in
      young patients. Further studies are needed to investigate this possible
      association and underlying mechanism.

PMID- 28496882
TI  - Conversion of Recent-Onset Atrial Fibrillation: Which Drug is the Best?
AB  - Introduction: Vernakalant is a new, safe and effective drug used intravenously.
      It has proven to be more rapid in converting recent onset atrial fibrillation
      (AF) to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide
      in clinical studies with few patients. At present no study has been conducted
      comparing these three drugs with a more substantial number of patients. The aim
      of our study is to compare the time to conversion to sinus rhythm, hospital stay
      and adverse events between vernakalant versus flecainide and propafenone in
      patients with a recent-onset AF. Materials and Methods: 150 hemodynamically
      stable patients with recent onset AF without structural heart disease were
      prospectively included. A single oral dose of propafenone 600 mg was administered
      to 50 patients; 50 patients received intravenous vernakalant; and 50 patients
      received a single oral dose of flecainide 300 mg. Clinical and laboratory
      variables were recorded. Results: Baseline characteristics were similar in the
      three groups.Time to conversion to sinus rhythm was 12 minutes in the vernakalant
      group versus 151 minutes in the propafenone group and 162 minutes in flecainide
      group (p< 0.01) The hospital stay was 243 minutes in the vernakalant group versus
      422 minutes in the propafenone group and 410 minutes in flecainide group (p<0.01)
      (Figure 2). No adverse events were reported. Conclusion: The time to conversion
      to sinus rhythm and hospital stay were statistically shorter in vernakalant group
      compared to flecainide and to propafenone. There were no adverse events in the
      three groups.

PMID- 28496883
TI  - Atrial Electrical Remodeling and Sleep Disordered Breathing.

PMID- 28496884
TI  - Left Atrial Thrombus Despite Anticoagulation: The Importance Of Homocysteine.
AB  - Patients in atrial fibrillation may have left atrial thrombi or strokes despite
      adequate anticoagulation. It is important to consider elevated plasma total
      homocysteine (tHcy) as a treatable clotting factor that may explain such cases.
      Metabolic B12 deficiency is common even in patients with a "normal" serum B12.
      Measurement of holotranscobalamin, methylmalonic acid or, in folate-replete
      patients, tHcy are necessary to diagnose metabolic B12 deficiency when the serum
      B12 is below 400 pmol/L. Elevated tHcy quadruples the risk of stroke in atrial
      fibrillation, and is far more common than the usual clotting factors for which
      testing is commonly performed: among patients attending.

PMID- 28496885
TI  - World Atrial Fibrillation Awareness Day - Time to Spread the Message.

PMID- 28496886
TI  - Highlights from the 5th Kansas City Heart Rhythm Symposium.

PMID- 28496887
TI  - Functional Pulmonary Vein Isolation During Atrial Fibrillation Ablation.
AB  - We report a case of apparent isolation of the right inferior pulmonary vein
      during atrial fibrillation ablation coincident with the onset of an atrial
      tachycardia. This report highlights the importance of assessing pulmonary vein
      conduction during sinus or paced rhythm at relatively long cycle length, rather
      than in atrial fibrillation or atrial tachycardia.

PMID- 28496888
TI  - Atrio-Esophageal Fistula After AF Ablation: Pathophysiology, Prevention
      &Treatment.
AB  - Atrioesophageal fistula is an extremely rare but often fatal late complication of
      atrial fibrillation ablation procedures resulting from massive thermal injury to
      the esophagus and surrounding structures. Causes of death include cerebral air
      embolism, massive gastrointestinal bleeding, and septic shock. Because of its
      exceptionally low rate of occurrence, no predictors of lesion development have
      been found and there has not been an uniform approach to either early diagnosis
      or corrective therapy. Currently, preventive strategies include empirically
      reducing power titration during PVI and/or while ablating the posterior left
      atrial wall, limiting energy delivery time and number, avoiding overlapping
      ablation lines as well as monitoring intraluminal esophageal temperature. In
      addition, it has been suggested to use conscious sedation rather than general
      anesthesia for better pain perception, monitoring intraprocedural esophageal
      position in relation to the posterior left atrium and extensive patient education
      regarding signs and symptoms of esophageal injury. Early diagnosis is essential
      to enable an aggressive treatment including stenting and/or surgical intervention
      to minimize the excessive morbidity and mortality associated with this condition.
      Unfortunately, despite application of such preventive measures, cases of complete
      atrial-esophageal fistula have still been reported.

PMID- 28496889
TI  - The Challenge of Chamber Stiffness Determination in Chronic Atrial Fibrillation
      vs. Normal Sinus Rhythm: Echocardiographic Prediction with Simultaneous
      Hemodynamic Validation.
AB  - Echocardiographic diastolic function (DF) assessment remains a challenge in
      atrial fibrillation (AF), because indexes such as E/A cannot be used and because
      chronic, rate controlled AF causes chamber remodeling. To determine if
      echocardiography can accurately characterize diastolic chamber properties we
      compared 15 chronic AF subjects to 15, age matched normal sinus rhythm (NSR)
      subjects using simultaneous echocardiography-cardiac catheterization (391 beats
      analyzed). Conventional DF parameters (DT, Epeak, AT, Edur, E-VTI, E/E') and
      validated, E-wave derived, kinematic modeling based chamber stiffness parameter
      (k), were compared. For validation, chamber stiffness (dP/dV) was independently
      determined from simultaneous, multi-beat P-V loop data. Results show that neither
      AT, Epeak nor E-VTI differentiated between groups. Although DT, Edur and E/E' did
      differentiate between groups (DTNSR vs. DTAF p < 0.001, EdurNSR vs. EdurAF p <
      0.001, E/E'NSR vs. E/E'AF p < 0.05), the model derived chamber stiffness
      parameter k was the only parameter specific for chamber stiffness, (kNSR vs. kAF
      p <0.005). The invasive gold standard determined end-diastolic stiffness in NSR
      was indistinguishable from end-diastolic (i.e. diastatic) stiffness in AF (p =
      0.84). Importantly, the analysis provided mechanistic insight by showing that
      diastatic stiffness in AF was significantly greater than diastatic stiffness in
      NSR (p < 0.05). We conclude that passive (diastatic) chamber stiffness is
      increased in normal LVEF chronic, rate controlled AF hearts relative to normal
      LVEF NSR controls and that in addition to DT, the E-wave derived, chamber
      stiffness specific index k, differentiates between AF vs. NSR groups, even when
      invasively determined end-diastolic chamber stiffness fails to do so.

PMID- 28496890
TI  - Performance of the Cockcroft-Gault, MDRD and CKD-EPI Formulae in Non-Valvular
      Atrial Fibrillation: Which one Should be Used for Risk Stratification?
AB  - Background: Renal dysfunction is a strong predictor of adverse events in patients
      with atrial fibrillation (AF). The Cokcroft-Gault, Modification of Diet in Renal
      Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI)
      equations are available for estimating the glomerular filtration rate (GFR). No
      comparisons between these equations have yet been performed in patients with non
      valvular AF concerning their mid-term prognostic performance. Methods: Cross
      sectional study of 555 consecutive patients with non-valvular AF undergoing
      transesophageal echocardiogram. We tested the prognostic performance of the
      aforementioned GFR estimation formulae, namely their ability to predict all-cause
      mortality (primary endpoint) and major cardiac adverse or ischemic
      cerebrovascular events (secondary endpoints) during an average follow-up of 24
      months. Results: Regarding the primary endpoint, Cockcroft-Gault (AUC=0.749+/
      0.028) was superior to both MDRD (AUC=0.624+/-0.039) and CKD-EPI (AUC=0.641+/
      0.034) [p<0.001 both comparisons] while CKD-EPI was superior to MDRD (p=0.011).
      Cockcroft-Gault was marginally superior to both MDRD (AUC=0.673+/-0.049 vs.
      AUC=0.586+/-0.054, p=0.041) and CKD-EPI (AUC=0.673+/-0.049 vs. AUC=0.604+/-0.054,
      p=0.063) in the prediction of ischemic cerebrovascular events, while no
      difference was found between CKD-EPI and MDRD. Concerning AUC for prediction of
      MACE, Cockcroft-Gault was superior to MDRD (p=0.009) and CKD-EPI (p=0.012), while
      CKD-EPI was similar to MDRD (p=0.215). Multivariate predictive models
      consistently included Cockcroft-Gault formula along with CHADS2, excluding the
      other two equations. Measures of reclassification revealed a significant
      improvement in risk stratification for all studied endpoints with Cockcroft-Gault
      instead of CKD-EPI. Conclusions: In patients with non-valvular AF, the Cockcroft
      Gault more appropriately classified individuals with respect to risk of all-cause
      mortality, ischaemic cerebrovascular event and major adverse cardiac event.

PMID- 28496891
TI  - Renin Angiotenin Blocker Pre-treatment and Recurrence After Pulmonary Vein
      Isolation in Patients with Paroxysmal and Persistent Atrial Fibrillation.
AB  - Introduction: Pulmonary venous isolation has emerged as an effective method for
      preventing atrial fibrillation (AF) recurrence. Yet, recurrence is common.
      Angiotensin-receptor-blockers (ARBs) and angiotensin-converting-enzyme-inhibitors
      (ACEI) are effective in reducing the extent of myocardial remodeling and
      fibrosis. Our aim was to study whether pretreatment with ARBs and ACEI was
      effective in decreasing recurrence after pulmonary vein isolation for patients
      with AF. Methods: Three hundred and twelve consecutive patients who underwent
      ablation from 12/2006 until 7/2010 were followed for at least one year. All
      patients underwent MRI before ablation to assess atrial fibrosis. Data include
      demographic characteristics, comorbidities, AF type and information regarding
      treatment with ACEI or ARBs. Results: Most patients were men (62%), mean age was
      64. Hypertension (HTN) was present in 60%. Their mean ejection fraction was 60%.
      There were 104 patients (33.3%) treated with ACEI, and 13.5 % were treated with
      ARBs prior to ablation. Ninety seven patients (31.1%) had AF recurrence. AF type
      was a significant predictor for recurrence (recurrence with paroxysmal,
      persistent and long-standing persistent: 23.75, 37.3 and 60%, respectively,
      p=0.005). The most important factor predicting recurrence was increased pre
      ablation atrial fibrosis (p<0.0001). Recurrence was more frequent in patients
      treated with ACEI (40.4% vs 26.4% untreated patients, p=0.012). In the ARB
      treated group, 38.1% vs 30.0% untreated experienced recurrence (p=0.3). After
      multivariable adjustment for demographics, risk factors and atrial fibrosis,
      treatment with ACEI was associated with increased rate of recurrence in patients
      with persistent AF (hazard ratio: 2.6, p=0.003). There was no significant
      relation between ACEI pretreatment and recurrence in patients with paroxysmal AF
      (HR- 0.83, p=0.7), or between ARB pre-treatment and recurrence in patients with
      paroxysmal as well as persistent AF (p=0.2 and 0.53, respectively). Conclusions:
      Pretreatment with ACEI or ARBs is not associated with reduced recurrence rate in
      patients with paroxysmal or persistent AF undergoing ablation.

PMID- 28496892
TI  - Electrophysiological Evaluation of Thoracoscopic Pulmonary Vein Isolation.
AB  - Although the majority of patients with atrial fibrillation and an indication for
      non-pharmacological therapy is treated with catheter ablation, thoracoscopic
      surgery is an emerging technique that aims at combining the results of the
      classic Cox Maze operation with a less invasive approach. Recurrences after
      thoracoscopic surgery have been mainly ascribed to incomplete ablation lines, but
      literature on electrophysiological confirmation of thoracoscopic pulmonary vein
      isolation is limited. Currently, surgical confirmation of uni- or bidirectional
      conduction block may be hampered by insufficient resolution of the mapping
      material available. Additionally uncertainty remains on the precise lesions sets
      required, and how to tailor them to individual patients. In hybrid procedures,
      electrophysiologists and surgeons join forces to combine their expertise and
      skills which may lead to increased procedural success rates by minimizing the
      chance of incomplete PV isolation or absence of conduction block across an
      alternative ablation line. Here we describe techniques for thoracoscopic mapping
      and present a literature review.

PMID- 28496893
TI  - Catheter Ablation Targeting Complex Fractionated Atrial Electrogram in Atrial
      Fibrillation.
AB  - The relatively low success rates seen with pulmonary vein ablation in non
      paroxysmal atrial fibrillation (AF) patients as compared to those with the
      paroxysmal form of the arrhythmia have prompted electrophysiologists to search
      for newer ablative strategies. A decade has passed since the initial description
      of complex fractionated atrial electrogram (CFAE) ablation aimed at targeting the
      electrophysiological substrate in atrial fibrillation. Despite intensive
      research, superiority of CFAE-based ablation over other contemporary approaches
      could not be demonstrated. Nevertheless, the technique has an adjunctive role to
      pulmonary vein ablation in non-paroxysmal AF patients. Perhaps our incomplete
      understanding of the complex AF pathophysiology and inadequate characterization
      or determination of CFAE has limited our success so far. This review aims to
      highlight the current challenges and future role of CFAE ablation.  .

PMID- 28496894
TI  - Atrial Fibrillation and Stroke Risk After Coronary Artery Bypass Grafting
      Surgery.
AB  - Background: The present multicentre study was aimed at determining the effect of
      preoperative atrial fibrillation (preop-AF) as stroke risk factor in coronary
      artery bypass graft surgery (CABG) during the perioperative period. Methods:
      Patients undergoing isolated CABG surgery were enrolled from 21 Spanish centers.
      Baseline variables related with perioperative stroke risk were recorded and
      analysed. The Northern New England Cardiovascular Disease Study Group (NNECVDSG)
      stroke risk schema was used to stratify stroke risk and compare predicted vs
      observed neurologic outcomes in this study. Results: 26347 patients were enrolled
      in the study. Prevalence of preop-AF was 4.2%, and was associated significantly
      with major cardiovascular comorbidities. The stroke rate was 1.38% (365 strokes),
      and it was slightly higher for patients with preop-AF vs non preop-AF, 1.82% vs
      1.36%, p = 0.2. NNECVDSG schema showed good predictive ability calculating the
      area under the receiver operating characteristic curve (c-statistic 0.696; 95% CI
      0.668 to 0.723). To investigate the associations of baseline preoperative
      variables with perioperative CABG-stroke a logistic regression model was
      performed. Preop-AF impact on perioperative stroke was lower that other
      variables. Preop-AF did not show an adverse impact in the quartiles groups
      according to NNECVDSG Stroke Risk Index. Conclusion: Risk of perioperative stroke
      in isolated CABG surgery patients is not significantly increased by preop-AF.

PMID- 28496895
TI  - Safety and Efficacy of Atrial Fibrillation Ablation in Young Patients.
AB  - Background: Outcome of catheter ablation of atrial fibrillation (AF) in young
      patients has not been widely reported. This study describes the safety and
      efficacy of radiofrequency catheter ablation (RFA) for atrial fibrillation in
      patients forty years or younger. Methods and Results: Forty consecutive patients
      who underwent fifty-two RFA procedures for symptomatic, drug-refractory
      paroxysmal or non-paroxysmal AF were included in the study. The mean (SD) age of
      the patients at time of initial procedure was 34.1 (5.6) years. Twenty-five
      (62.5%) patients had paroxysmal AF, 6 (15%) patients had persistent AF, and 9
      (22.5%) patients had longstanding persistent AF. Procedural safety and efficacy
      were assessed based on patient status > 1 year after initial ablation procedure.
      After a mean (SD) follow-up of 3.8 (2.9) years, 25 (62.5%) patients were free of
      AF without antiarrhythmic drugs (AAD) and 40 (100%) patients experienced > 95%
      reduction of AF burden on or off AADs. No major complications or adverse events
      occurred during the study. Conclusions: Catheter ablation of AF is a favorable
      therapeutic option for patients 40 years or younger, resulting in high rates of
      procedural success with a low risk of major complications.

PMID- 28496896
TI  - Left Atrial Appendage Occlusion for Stroke Prevention in Patients with
      Nonrheumatic Atrial Fibrillation.
AB  - Introduction: Atrial fibrillation is a common rhythm disorder, which is related
      to a higher risk of thrombembolism resulting in a high rate of cerebral stroke or
      transient ischemic attacks. According to the CHADS2- or CHA2DS2Vasc-Score there
      is an indication for oral anticoagulation to prevent patients from mostly
      disabling strokes. However, more than 50% of patients are not adequately treated
      with oral anticoagulation due to different reasons, especially contraindications.
      More than 90% of thrombi develop in the left atrial appendage (LAA), which lead
      to the idea of developing devices to exclude the LAA from the systemic
      circulation to prevent patients from embolisations. Another approach is surgical
      ligation or removal of the LAA during operation procedures. Content: Different
      devices and their clinical data are discussed in this review. Available
      literature for most of the devices is evaluated and last but not least some
      surgical results are discussed at the end. Existing data of randomized and non
      randomized studies show that the concept of LAA-occlusion instead of
      anticoagulation therapy works. However, complication rates during intervention
      have to be kept in mind, but with adequate training also new and inexperienced
      operators can do the procedure safely. Most data and the only randomized studies
      are available for the Watchman Device. Despite some few complications like
      pericardial effusions, bleeding complications and thrombus formation on the
      devices, the data showed a non inferiority of device-implantation in comparison
      with anticoagulation therapy in the first few years. In long term follow up more
      than 4 years after implantation, there is even a superiority of the device
      compared with anticoagulation therapy, safety issues are no longer significantly
      different despite some periprocedural complications. This has to be reflected
      with the background, that operators could treat 3 patients with a totally new
      method, thereafter all patients had to be randomized into the study. So
      experience was limited in the first phase of this trial. Surgical data vary much
      due to different techniques of LAA-occlusion. With newer devices results are also
      promising. Conclusion: LAA-occlusion is a developing field of interventional and
      surgical techniques. The concept of LAA-occlusion could be proved in one
      randomized trial. At least for patients contraindicated for anticoagulation
      therapy, LAA-occlusion is a real alternative to only aspirin therapy or doing
      nothing. With emerging techniques and lower complication rates, LAA-occlusion
      might develop to a real alternative to anticoagulation therapy, at least for
      vitamin-K-antagonists. There are no data available so far in comparison with new
      oral anticoagulants. Further studies are needed to compare device therapy with
      new oral anticoagulants.

PMID- 28496897
TI  - Comparing Safety and Efficacy of Irrigated Radiofrequency Catheter Ablation
      Versus Combined Cryoballoon and Catheter Ablation for Persistent Atrial
      Fibrillation.
AB  - Background: Catheter and cryoballoon ablation are established treatments for
      atrial fibrillation. Frequently, substrate modification of the left atrium is
      performed in patients with persistent AF or evidence of left atrial adverse
      remodeling. We compared one year outcomes of AF ablation with substrate
      modification utilizing radiofrequency catheter ablation (RFA) compared to a
      combination of cryoballoon ablation with radiofrequency catheter ablation (HAFA).
      Methods: Ablation for persistent AF was performed using stand-alone catheter
      ablation (RFA group, n=31) or cryoballoon for pulmonary vein isolation with RFA
      catheter ablation for substrate modification (HAFA group, n=21) and procedural
      and clinical outcomes were analyzed. Pulmonary vein isolation and LA substrate
      modification including creation of left atrial ablation lines and/or CFAEs was
      performed in all patients. Patients were followed for up to one year. A three-
      month blinding window was applied for analysis. Results: Clinical characteristics
      were similar between groups. Total procedure (244.15+/-64.7 vs 235.5+/-54.6,
      p=0.6) and fluoroscopy time (37+/-15.4 vs 29.5+/-15.7, p=0.96) were not different
      between the HAFA and RFA groups, respectively. Periprocedural complications were
      similar among groups. AF free survival was not significantly different between
      Conclusions: Combined cryoballoon and catheter ablation for LA substrate
      modification (HAFA) has similar safety and efficacy compared to stand-alone
      catheter ablation for persistent AF. Recurrent atrial flutter is more frequently
      observed after cryoballoon ablation for persistent AF.

PMID- 28496898
TI  - Durable Pulmonary Vein Isolation: The Holy Grail of Atrial Fibrillation Ablation.
AB  - The inability to achieve durable pulmonary vein isolation remains a major
      limitation to catheter ablation for the treatment of atrial fibrillation (AF). In
      this review, we discuss the research performed over the past decade investigating
      methods to improve lesion permanence for the goal of durable pulmonary vein
      isolation (PVI). Investigations evaluating procedural techniques, adjunctive
      pharmacologic therapy, and newer energy sources designed to improve ablation
      lesion permanence are discussed.

PMID- 28496899
TI  - Role of Preprocedural Imaging in Catheter Ablation of Atrial Fibrillation.
AB  - Catheter ablation is a well established and widely used therapy option of atrial
      fibrillation. The use of 3D mapping systems to aid the ablation process has
      become standard in most centers. Whether preprocedural imaging is an asset to
      catheter ablation procedures is of debate. Available methods and the existing
      evidence are outlined in this article.

PMID- 28496900
TI  - Electrophysiological Evaluation of Pulmonary Vein Isolation.
AB  - Since the pulmonary veins (PVs) were identified as a major source of AF triggers,
      ablation strategies targeting the PVs have evolved from focal ablation inside the
      PVs to wide area circumferential PV isolation (PVI) which at this juncture is the
      standard approach. Despite the widespread popularity of PVI, a universal
      definition is lacking. While "entrance block" is a generally accepted endpoint
      for PVI, the role of "exit block" has yet to be determined. Inexcitability of the
      circular ablation line has been introduced as a promising additional endpoint for
      PVI and was associated with an improved clinical outcome in a randomized trial.
      Correct interpretation of PV electrograms during an ablation procedure is
      critical in terms of efficacy and safety. A variety of electrophysiological
      techniques help to correctly differentiate components of complex PV electrograms.
      Resumption of PV conduction after initially successful PVI leading to AF
      recurrence remains a major problem and confirmation of bi-directional conduction
      block does not exclude reversible tissue damage along the ablation line.
      Prolongation of post-PVI monitoring and application of provocative procedures
      such as the administration of adenosine after initial PVI to unmask dormant PV
      conduction may improve clinical outcome although there is lack of valid data
      supporting these strategies. This article aims on clarifying the
      electrophysiological criteria for complete pulmonary vein isolation and the
      explain the importance of this cornerstone in almost all atrial fibrillation
      ablation procedures.

PMID- 28496901
TI  - Role of Inflammation in Initiation and Perpetuation of Atrial Fibrillation: A
      Systematic Review of the Published Data.
AB  - Inflammation has emerged as being strongly associated with AF initiation and
      perpetuation, including being implicated as a possible causal factor. Its role
      needs further elucidation to assist with the optimal prevention and treatment of
      AF using an individualized strategy. In the present review article the current
      published data linking inflammation to AF is summarized.

PMID- 28496902
TI  - Impaired Erythrocyte Deformability in Patients with Coronary Risk Factors:
      Significance of Nonvalvular Atrial Fibrillation.
AB  - Although coronary risk factors promote the formation of atherosclerotic plaque
      containing activated platelets and inflammatory leukocytes, and play a pivotal
      role in the development of coronary artery diseases (CAD), the hemorheological
      effects of these risk factors on circulating intact erythrocytes, a major
      component of whole blood cells, are poorly understood. Therefore, this study
      aimed to quantify erythrocyte deformability in patients with coronary risk
      factors, and enrolled 320 consecutive cardiac outpatients including 33 patients
      with nonvalvular atrial fibrillation (AF). Patients with acute coronary syndrome
      or valvular AF were excluded. Demographic variables obtained by medical records
      were correlated with erythrocyte deformability investigated by our highly
      sensitive and reproducible filtration technique. Among demographic variables,
      triglyceride (p = 0.004), HbA1c (p = 0.014) and body weight (p = 0.020) showed
      significant inverse correlation to the erythrocyte deformability. This
      deformability was not associated with types of CAD (old myocardial infarction vs.
      stable angina) or modality of treatment (percutaneous intervention vs. coronary
      artery bypass grafting). Unexpectedly, stepwise multiple regression analysis
      demonstrated that nonvalvular AF was the most significant contributor to the
      impaired erythrocyte deformability (p = 0.002). Hypertension and dyslipidemia are
      more prevalent in the AF patients (p < 0.001), and the erythrocyte deformability
      was found to be impaired synergistically and significantly (p < 0.001) during the
      stepwise accumulation of the coronary risk factors in addition to AF. In
      conclusion coronary risk factors synergistically impair the erythrocyte
      deformability, which may play an important role in critically stenotic coronary
      arteries. Since the impairment of intact erythrocyte deformability is mostly
      associated with nonvalvular AF, this common arrhythmia may reflect the coronary
      risk accumulation.

PMID- 28496904
TI  - Happy Holidays.

PMID- 28496903
TI  - Exploring the Potential Role of Catheter Ablation in Patients with Asymptomatic
      Atrial Fibrillation: Should We Move away from Symptom Relief?
AB  - Although silent atrial fibrillation (AF) accounts for a significant proportion of
      patients with AF, asymptomatic patients have been excluded from AF ablation
      trials. This population presents unique challenges to disease management. Recent
      evidence suggests that patients with asymptomatic AF may have a different risk
      profile and even worse long-term outcomes compared to patients with symptomatic
      AF. For the same reasons they might be more prone to side-effects of
      antiarrhythmic drugs, including pro-arrhythmias. The poor correlation between
      symptoms and AF demonstrated in several studies should caution physicians against
      making clinical decisions depending on symptoms. Although current guidelines
      recommend AF ablation only in patients with symptoms, more attention should be
      paid to the AF burden and a rhythm control strategy has the potential to improve
      morbidity and mortality in AF patients. However, limited data exist regarding the
      use of catheter ablation for asymptomatic AF patients. As ablation techniques
      have improved, AF ablation has become more widespread and complication rate
      decreased. As a result, referrals of asymptomatic patients for catheter ablation
      of AF are on the rise. In this review we discuss the many unresolved questions
      concerning the role of the ablative approach in asymptomatic patients with AF.

PMID- 28496905
TI  - Role of Bi-Atrial Pacing In Slowing The Progression of Paroxysmal Atrial
      Fibrillation To Permanent Atrial Fibrillation.
AB  - Introduction: Bi-atrial lead placement combined with atrial overdrive pacing has
      demonstrated a reduction in percent time mode switched and mode switches per day.
      This retrospective analysis compared long term outcomes of patients with right
      atrial overdrive pacing alone (DAO) to patients having atrial overdrive with bi
      atrial leads (BIA) in slowing the progression of paroxysmal atrial fibrillation
      (PAF) to permanent continuous atrial fibrillation (CAF). Methods: Thirty-three
      patients age 76.6 (+/-1.96) from our prior investigation were selected. The DAO
      control group (N=16) had received a standard right atrial pacing lead. The BIA
      group (N=17) had pacing leads placed in the right atrium and coronary sinus.
      Patients were followed for a mean 1217 days (+/-838). Days of CAF was classified
      as the date of final mode switch until analysis. Results: A total of 40,171
      follow-up days were evaluated. The mean follow-up for both cohorts was 1217 days
      (+/-838). The DAO group consisted of 15,318 days (mean 957 +/-761) and the BIA
      group 24,853 days (mean 1461 +/-854). A lower total number of days were spent in
      CAF in the BIA group versus the DAO group, 1380 vs 2197 respectively. Corrected
      for follow-up duration, 5.55% days in CAF was seen in the BIA group vs. 14.34% in
      the DAO group which did not reach statistical significance. Conclusions: Although
      BIA overdrive pacing initially demonstrated reduced time in mode switch compared
      to DAO alone, this analysis did not detect a reduction in progression to CAF.
      More subjects or a longer follow up would be needed.

PMID- 28496906
TI  - Risk of Cardiovascular Events, Stroke, Congestive Heart Failure, Interstitial
      Lung Disease, and Acute Liver Injury: Dronedarone versus Amiodarone and Other
      Antiarrhythmics.
AB  - No published studies have evaluated the risks of cardiovascular (CV) events,
      stroke, congestive heart failure (CHF), interstitial lung disease (ILD), and
      severe acute liver injury (ALI) related to antiarrhythmics treatment in real
      world clinical practice setting. We examined the relationship between the above
      events and the selected antiarrhythmics in the real-world setting in the US.
      Using a retrospective cohort design, the hazard ratios of the outcome events were
      analyzed from 10,455 adult patients with a diagnosis of atrial
      fibrillation/atrial flutter and a new treatment with dronedarone (comparison
      drug), amiodarone, sotalol, flecainide, or propafenone between 07/20/2009 and
      12/31/2010 from the Clinformatics Data MartTM database. The patients were
      followed until: 1) switch to another antiarrhythmic drug, 2) occurrence of the
      outcome event, 3) end of enrollment, or 4) end of the study period, whichever
      occurred first. No significant differences were observed in the hazard ratios of
      the outcome events between dronedarone, amiodarone, and the other
      antiarrhythmics, except that amiodarone was associated with a higher risk of CV
      events (adjusted HR = 1.7, 95%CI: 1.1-2.4) and stroke (adjusted HR = 2.0, 95%CI:
      1.33.2), compared to dronedarone, especially amongst patients without a CHF
      history (adjusted HR = 2.4, 95%CI: 1.4-3.8 and 2.2, 95%CI: 1.23.9). A higher risk
      of CHF was also associated with amiodarone in patients without history of CHF at
      baseline (adjusted HR = 2.7, 95%CI: 2.03.6). In this real-world investigation, no
      difference in risk was observed between dronedarone, sotalol, and propafenone
      initiators for CV events, stroke, CHF, ILD, and ALI. Amiodarone was associated
      with higher risks of CV events, stroke, and CHF than dronedarone in patients
      without a CHF history, indicating dronedarone could be an alternative therapy
      option with lower risk of CV events than amiodarone for the above patients.

PMID- 28496907
TI  - Mid-term Risk Stratification of Patients with a Myocardial Infarction and Atrial
      Fibrillation: Beyond GRACE and CHADS.
AB  - Background: We hypothesize that the discriminative performance of GRACE, ACHTUNG
      Rule, CHADS2 or CHA2DS2-VASc may be lower in patients with a Myocardial
      Infarction (MI) and concurrent atrial fibrillation (AF), as none of these scores
      seem able to fully capture both atherothrombotic/thromboembolic risks. This study
      aims to evaluate the mid-term prognostic performance of these algorithms in
      patients with these two conditions and to analyze the utility of a score
      combining GRACE and CHA2DS2-VASc. Methods: Observational retrospective single
      centre cohort study including 1852 patients admitted with a MI. We tested the
      prognostic performance of the aforementioned risk stratification schemes in
      patients with vs. without AF at admission or during hospitalization. Primary
      endpoints: a) total all-cause mortality, comprising intrahospital and post
      discharge all-cause mortality; b) intrahospital all-cause mortality and c) all
      cause mortality during follow-up. Furthermore, all three versions of the ACHTUNG
      Rule were directly compared to their equivalent GRACE score versions, and a new
      score, entitled GRACE-CHA2DS2-VASc, was developed and compared with GRACE.
      Results: The mid-term prognostic performance of all scores was considerably lower
      in patients with AF, corroborating our hypothesis. The ACHTUNG-Rule seemed
      superior to GRACE in the prediction of post-discharge (AUC 0.790+/-0.032 vs.
      0.685+/-0.038, p=0.079; integrated discrimination improvement index [IDI] of
      0.166 and relative IDI of 83.7%) and total mortality (0.762+/-0.031 vs. 0.712+/
      0.033, p=0.144; IDI of 0.042, relative IDI of 11.7%), but its performance
      decreased in those with AF as well. GRACE-CHA2DS2-VASc was only marginally
      superior to GRACE in discriminative performance, but detected truly low- (CHA2DS2
      VASc <2; total mortality 0%) and high-risk patients (GRACE high-risk stratum, and
      CHA2DS2-VASc >4; total mortality 44.3%) with considerable efficacy. Conclusions:
      In patients with MI and concurrent AF, the GRACE, CHADS2 and CHA2DS2-VASc scores
      seemed less accurate in the prediction of all-cause mortality. A hypothetic GRACE
      CHA2DS2-VASc score or the recently developed ACHTUNG-Rule may eventually provide
      a more rigorous approach to risk stratification in this high-risk setting.

PMID- 28496909
TI  - Detection of Recurrent Atrial Fibrillation Utilizing Novel Technology.
AB  - The true prevalence of AF is likely underestimated because episodes are often
      sporadic and challenging to detect in a "real world" setting. This case report
      will describe a 58-year-old atrial fibrillation patient with multiple cardiac
      risk factors. After two ablations and one cardioversion, the patient failed to
      remain in normal sinus rhythm. Shortly after AF returned, the decision was made
      to perform a second cardioversion. Post-procedure, the patient was given a novel
      FDA-approved, wireless ECG monitoring device compatible with the iPhone(r). This
      device has the capability of recording and transmitting a single-channel ECG.
      Within days, the patient began feeling symptomatic again and used his device to
      transmit an ECG to his healthcare provider. Recurrent AF was detected and the
      patient was directed to seek further evaluation. The success of this novel device
      to detect recurrent AF highlights the "real world" applicability of using mHealth
      technology more readily in patient care.

PMID- 28496908
TI  - Advances in Left Atrial Appendage Occlusion Strategies.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and
      associated with an elevated risk of thromboembolic stroke and systemic
      embolization. The evidence suggests that ~90% of thrombi in patients with non
      valvular AF are localized to the left atrial appendage (LAA). Therefore, it seems
      reasonable to consider LAA exclusion in selected patients with AF for stroke
      prevention. LAA exclusion can be achieved through a variety of surgical and
      percutaneous techniques. Surgical methods include LAA amputation, ligation,
      clipping and stapling. Whereas percutaneous strategies consist of endocardial
      closure using an LAA occlusion device and epicardial LAA ligation using a snare
      device. Even though several trials and registries of LAA exclusion have yielded
      promising outcomes, at this time evidence for long term safety and efficacy seems
      insufficient to recommend this approach to all patients with non-valvular AF.
      Future prospective randomized trials are needed to assess the precise role for
      these therapeutic options. Furthermore, there is a paucity of data on the
      comparison of these strategies to the novel oral anticoagulants which also
      deserves further attention. This review will carefully examine the current LAA
      exclusion techniques and the available data.

PMID- 28496910
TI  - Cardiac Arrest from Asystole During Endoscopic Retrograde
      Cholangiopancreatography: A Rare But Fatal Complication.
AB  - We present a rare complication of cardiac arrest from asystole in the setting of
      prolonged endoscopic retrograde cholangiopancreatography(ERCP) procedure.
      Cardiopulmonary complications of ERCP are rare but can be fatal. Therefore it is
      essential to closely monitor the patient during ERCP. Immediate access to
      resuscitation equipment facilitating prompt intervention in the unlikely event of
      fatal cardiovascular collapse should be a part of standard ERCP protocol to
      ensure life threatening complications are appropriately managed.

PMID- 28496911
TI  - Anticoagulation and Clinical Outcomes in Heart Failure Patients With Atrial
      Fibrillation: Findings From the ADHERE Registry.
AB  - The risks and benefits of anticoagulation for patients with both heart failure
      and atrial fibrillation are unclear. We hypothesized that anticoagulation was
      associated with improved clinical outcomes of heart failure patients with atrial
      fibrillation independent of other risk factors. We conducted a retrospective
      cohort study of clinical registry data linked to Medicare claims for new users of
      oral anticoagulation (warfarin) without contraindications, discharged home alive,
      and stratified by CHADS2 score. Outcomes of interest were propensity score
      adjusted estimates of the effects of warfarin at discharge on all-cause
      mortality, thromboembolic events, major adverse cardiovascular events, and
      bleeding events. Among 10,494 patients with heart failure and atrial
      fibrillation, the 2249 patients newly treated with warfarin had lower 1-year
      mortality (27.7% vs 39.3% for CHADS2 score <= 3 [P > .001]; 31.6% vs 41.8% for
      CHADS2 score > 3 [P > .001]) than patients not treated with warfarin. There was
      no significant difference in thromboembolic events, major adverse cardiovascular
      events, or bleeding events at 1 year. After multivariate adjustment, exposed
      individuals in both CHADS2 subgroups had lower adjusted 1-year mortality (CHADS2
      <= 3: hazard ratio, 0.78 [95% confidence interval, 0.69-0.89]; CHADS2 >3: 0.78
      [0.66-0.93]). In conclusion, warfarin use in heart failure patients with atrial
      fibrillation was associated with improved survival at 1 year independent of
      baseline CHADS2 score. However, there was no significant reduction in clinical
      events, such as thromboembolic or major adverse cardiovascular events at 1 year
      that might simply explain the survival benefit associated with warfarin.

PMID- 28496912
TI  - Presence of A Left Atrial Appendage Thrombus After Successful Surgical Closure of
      the Left Atrial Appendage: A Case Report.
AB  - A 64-year-old African American woman presented for defibrillator threshold
      testing (DFTs) after a recent hospitalization for ventricular fibrillation
      terminated by her ICD. She had a known history of non-ischemic cardiomyopathy,
      atrial fibrillation, rheumatic mitral valve disease s/p mitral valve replacement
      and a redo after subsequent endocarditis. In preparation for the DFTs, the
      patient underwent a transesophageal echocardiogram (TEE) to rule our left atrial
      (LA) or LA appendage thrombus. Patient was found to have a surgically closed
      appendage. Within the body of the closed appendage, a mobile thrombus was seen
      with clot free areas surrounding the thrombus. Doppler and contrast studies
      confirmed that there was no communication between the LA and the appendage. The
      patient underwent DFTs without complication and a follow-up TEE confirmed the
      presence of the clot in the non-communicating LA appendage.

PMID- 28496913
TI  - Role of PR-Interval In Predicting the Occurrence of Atrial Fibrillation.
AB  - The identification of individuals at high risk of developing atrial fibrillation
      (AF) is important to prevent potentially lethal and invalidating complications of
      this arrhythmia. Recently, several studies have investigated the association
      between PR-interval and the risk of AF and have tested the value of PR-interval
      in personalized risk scores for AF. However, the results of these studies are
      generally conflicting. When looking for an association between a prolonged PR
      interval (first-degree atrioventricular [AV] block vs. normal PR-interval) and an
      increased risk of AF, not all studies were able to find a consistent and
      statistically significant association. In two recent studies, however, the
      investigators were able to show an increased risk of AF for individuals with PR
      intervals in the short range compared with individuals in the middle range. The
      existence of a true U-shaped relationship could potentially explain part of the
      conflicting results from investigators only looking for an increased risk for
      longer PR-intervals. However, regardless of these speculations, the association
      seems relatively weak. The significance of PR-interval in risk prediction of AF
      has been tested in three independent risk scores where model selection primarily
      was based on improvement in c-statistics. In one risk score, PR-interval improved
      the predictive value of the risk model, whereas it did not in the other two risk
      scores. Further studies are warranted before any final conclusion can be drawn,
      although based on the current evidence, it is reasonable to conclude that the
      predictive value of PR-interval in AF risk prediction is limited.

PMID- 28496914
TI  - Non-Fluoroscopic Transseptal Catheterization During Electrophysiology Procedures
      using a Remote Magnetic Navigation System.
AB  - Transseptal punctures are commonly performed, and left atrial (LA) access is
      frequently lost during lengthy, complex electrophysiology (EP) procedures. We
      describe a new technique for non-fluoroscopic re-crossing the fossa ovalis using
      a new multielectrode transseptal sheath (TS) and a new remote magnetic catheter
      navigation system (RMNS) (CGCI System, Magnetecs) that uses 8 rapid external
      electromagnets for real-time navigation of a magnet-tipped electrode catheter
      across the initial transseptal puncture site in 5 patients undergoing left-sided
      ablation procedures. The three-dimensional (3D) position of a 8.5 Fr steerable TS
      with 5-ring 5-15-15-5-mm spaced distal electrodes (Agilis ES(c), St Jude
      Medical), and site of fossal ovalis crossing were "shadowed landmarks" on a 3D
      electroanatomic mapping (EAM) system (EnSite/NavXTM, St Jude Medical). The TS
      magnetic ablation catheter assembly was pulled-back to the inferior vena cava.
      EAM landmarks were used with RMNS-guided "manual" and "automated" catheter
      navigation modalities, until septal crossing was obtained. Transseptal re
      crossing was successfully performed in all patients in 6.2+/-8.1 sec using the
      "automated" RMNS-guided technique and in 30.4+/-28.4 sec using the "manual" RMNS
      guided technique (p=0.01) without complications. This new RMNS was safely and
      effectively used to perform non-fluoroscopic transseptal catheterization.

PMID- 28496916
TI  - Cardioversion in Acute Atrial Fibrillation Without Anticoagulation.
AB  - A major concern in cardioversion of newly detected atrial fibrillation is the
      risk of thromboembolic events. The vast majority of these events occur in the
      first week following cardioversion. Transesophageal echocardiography has
      demonstrated that thrombus and dense spontaneous echo contrast may occur in the
      left atrium and left atrial appendage in patients with acute atrial fibrillation
      (<48 hours) scheduled for cardioversion. Moreover, atrial function may become
      impaired immediately following successful cardioversion. The risk of
      thromboembolic events increases with the presence of stroke risk factors, such as
      heart failure, hypertension, diabetes, prior stroke, female sex and age above 65
      75 years. Thus, the current guidelines of the ESC and ACC/AHA/Heart Rhythm
      Society recommend that patients with acute atrial fibrillation should undergo
      cardioversion under cover of unfractionated or low-molecular weight heparin
      followed by oral anticoagulation for at least 4 weeks in patients in patients at
      moderate-to-high risk for stroke. In line with the guidelines, new evidence from
      a large patient population suggests that after successful cardioversion of acute
      atrial fibrillation, patients have a low overall risk of thromboembolic events
      without any anticoagulation when they have no risk factors for thromboembolism.
      In contrast, the risk is in the range of 10% in patients with multiple classic
      risk factors for thromboembolism.

PMID- 28496915
TI  - Atrial Fibrillation and Stroke - Increasing Stroke Risk With Intervention.
AB  - In this review, we focus on the important newly recognized appreciation for the
      paradoxical increase in stroke and TIA as a result of intervention meant to treat
      atrial fibrillation (AF) with the hope of decreasing stroke risk in the long
      term. The impact of silent cerebral lesions recently appreciated as a potentially
      major limitation and risk with AF ablation is explained. We categorize our
      present understanding of how we can minimize risk and provide a platform for what
      will undoubtedly be newer study, changes in the way procedures are done today,
      and possibly vascular-based stroke-reduction strategies.

PMID- 28496917
TI  - Utility of the Pulmonary Vein Ablation Catheter for Electrical Isolation of A
      Left Sided Vena Cava Triggering Atrial Fibrillation.
AB  - A persistent left sided vena cava (LSVC) can trigger atrial fibrillation. A 41
      year old man with paroxysmal atrial fibrillation (PAF) and LSVC had all four
      pulmonary veins and his LSVC electrically isolated from the left atrium with the
      Pulmonary Vein Ablation Catheter (PVAC). At follow up patient described no
      further episodes of AF. Single-shot ablation catheters such as the PVAC maybe
      successfully and safely used for electrical isolation of a LSVC, though clearly
      more experience is required to comprehensively evaluate this.

PMID- 28496918
TI  - Cardiac Events Theoretically Cannot Be Produced By Non-Ischemic And/Or Iso
      Ischemic Myocardium: Challenging Postulations And Vitality Of The Concept Of
      "Ischemia-Dependent Conflictogenic Arrhythmias".
AB  - Ischemia plays a key role in cardiac arrhythmogenesis, particularly in elderly
      patients. Healthy, non-ischemic and structurally normal myocardium is universally
      free from dysrhythmias. Thereby intact coronary blood flow prevents potential
      cardiac events. Hypothetically, ischemia-related electrophysiological differences
      are responsible for the supraventricular and/or ventricular rhythm
      irregularities. The goal of this review is to determine the role of systemic and
      coronary circulatory peculiarities and their association with heart rhythm
      abnormalities. The current analytical review extends and enriches previous
      knowledge about the influence of these peculiarities on the genesis of ischemia
      dependent conflictogenic arrhythmias. Different intensity of coronary blood flow
      resulting from stenotic obstacles or vasospasm potentially leads to the non
      uniform perfusion of myocites thus creating albeit subtle but vulnerable and
      powerful electrophysiologic substrate impending cardiac rhythm disturbances.
      Apparently, the behavior of both non-ischemic and iso-ischemic myocardium in
      respect to electric cardiac activity is very similar, at least theoretically.
      Some different clinical entities, e.g. arterial hypotension and/or anemia
      containing ischemic component, in most cases are free from arrhythmias. This
      postulation may be helpful in furthering arrhythmogenicity insights which have
      been generated previously. On the contrary, increased blood pressure often
      concurs with the supraventricular and/or ventricular arrhythmias; this pattern
      also favorably reflects our previous hypothetical assumptions associated with the
      mechanisms of arrhythmogenesis. Conclusively, both non-ischemic and iso-ischemic
      myocardium may be attributed to nonarrhythmogenic milieu. Nevertheless, the
      inventive analysis and more explorative data are required to support the
      suggested postulations.

PMID- 28496920
TI  - Testing Of Box Lesion By Adenosine.

PMID- 28496921
TI  - Atraumatic Lung Hernia: A Rare Complication of Minimally Invasive Surgical Atrial
      Fibrillation Ablation.
AB  - Lung herniation after minimally invasive thoracoscopic pulmonary vein ablation
      has never been described before so far. We report for the first time, of its
      incidence in a 62-year-old patient, 6 weeks after a minimally invasive cardiac
      surgery (MICS) for atrial fibrillation ablation. We suggest that even after MICS,
      a high resolution computerized tomography scan should be performed in patients
      presenting with breathing difficulty and chest pain to rule out this condition
      too, other than pulmonary vein stenosis.

PMID- 28496922
TI  - More Progress in Atrial Fibrillation Education and Management.

PMID- 28496924
TI  - Atrial Fibrillation Triggered By Drug-Induced Bradycardia.
AB  - Atrial fibrillation (AF) is the most frequently observed arrhythmia in clinical
      practice. Many causative factors have been identified from well-known structural
      heart disease to less understood triggers. Both sympathetic and parasympathetic
      (vagal) stimuli are able to trigger paroxysms of AF. Vagally mediated AF is
      especially observed in young healthy subjects and especially during nights when
      the heart rate is considerably slow. Tachycardia induced AF is demonstrated and
      the possible mechanisms are explained. However, a case of bradycardia induced AF,
      thus far, hasn't been reported. Here we present a case of AF induced by severe
      bradycardia which was triggered by concomitant use of beta-blockers and
      diltiazem.

PMID- 28496923
TI  - Emergency Covered Stent Implantation For Rupture Of A Pulmonary Vein After
      Balloon Angioplasty For Postinterventional Pulmonary Vein Stenosis.
AB  - Pulmonary vein (PV) stenosis is a known complication of PV isolation procedures
      for atrial fibrillation. We describe in this report a case of emergency covered
      stent implantation for rupture of a PV after balloon angioplasty for
      postinterventional PV stenosis occlusion. Focus is on stent implantation and on a
      novel aspect of magnetic resonance imaging for postprocedural outcome evaluation.
      A focused review of the current literature regarding ongoing limitations of PV
      stenosis treatment is provided.

PMID- 28496919
TI  - Structural and Functional Remodeling of the Left Atrium: Clinical and Therapeutic
      Implications for Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical
      practice. Despite advances in our understanding of the pathophysiology of this
      complex arrhythmia, current therapeutic options remain suboptimal. This review
      aimed to delineate the atrial structural and functional remodeling leading to the
      perpetuation of AF. We explored the complex changes seen in the atria in various
      substrates for AF and the therapeutic options available to prevent these changes
      or for reverse remodeling. Here we also highlighted the emerging role of
      aggressive risk factor management aimed at the arrhythmogenic atrial substrate to
      prevent or retard AF progression.

PMID- 28496925
TI  - Cryoballoon versus Radiofrequency Ablation for Atrial Fibrillation: A Meta
      analysis of 16 Clinical Trials.
AB  - Introduction: We aimed to study the procedural characteristics, efficacy and
      safety of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) for
      catheter ablation of paroxysmal atrial fibrillation (AF). Methods: A systematic
      literature search was performed using PubMed, EMBASE, Web of Science, and
      Cochrane Central Register of Controlled Trials to clinical trials comparing CBA
      and RFA for AF. Outcomes were evaluated for efficacy, procedure characteristics
      and safety. For each study, odd ratio (OR) and 95% confidence intervals (CIs)
      were calculated for endpoints for both approaches. Results: We analyzed a total
      of 9,957 participants (3,369 in the CBA and 6,588 in RFA group) enrolled in 16
      clinical trials. No significant difference was observed between CBA and RFA with
      regards to freedom from atrial arrhythmia at 12-months, recurrent atrial
      arrhythmias or repeat catheter ablation. CBA group had a significantly higher
      transient phrenic nerve injury (OR 14.19, 95% CI: 6.92-29.10; p<0.001) and
      persistent phrenic nerve injury (OR 4.62, 95% CI: 1.97-10.81; p<0.001); and a
      significantly lower pericardial effusion/cardiac tamponade (OR 0.43, 95% CI: 0.26
      0.72; p=0.001), and groin site complications (OR 0.60, 95% CI: 0.38-0.93;
      p=0.02). No significant difference was observed in overall complications,
      stroke/thromboembolic events, major bleeding, and minor bleeding. Conclusion: CBA
      was non-inferior to RFA for catheter ablation of paroxysmal AF. RF ablation was
      associated with a higher groin complications and pericardial effusion/cardiac
      tamponade, whereas CBA was associated with higher rates of transient and
      persistent phrenic nerve injury.

PMID- 28496926
TI  - Novel Ventricular Repolarization Indices in Patients with Coronary Slow Flow.
AB  - Background: Coronary slow flow (CSF) phenomenon is described angiographically as
      delayed progression of the injected contrast agents through the coronary
      arteries. Aim of this study was to analyze ventricular repolarization in CSF
      patients by using Tpeak-Tend interval, Tpeak-Tend/QT ratio, Tpeak-Tend/QTc ratio
      and other repolarization parameters since these parameters are used as predictors
      for ventricular arrhythmogenesis. Materials and Methods: We have retrospectively
      analyzed diagnostic coronary angiography results of 160 patients between 2010 and
      2014. Patients were divided into two groups according to coronary flow results.
      CSF group consisted of 33 female, 82 male patients with mean age 51,9+/-11,5
      years. Control group included patients with normal coronary flow; 13 female, 32
      male with mean age 50,8+/-11,7 years. In all patients, ventricular repolarization
      parameters as well as other associated electrocardiographic intervals were
      measured on the twelve-lead surface electrocardiogram. Results: The ventricular
      repolarization parameters: QTmax interval, QTmin interval, QTc, QTI, QTcI, JTmax
      interval, JTmin interval, JTdispersion and JTIndex were not significantly
      different between the groups. However followings parameters differed
      significantly between patients and controls; QRS (92,8+/-11,5 msn versus 78,3+/
      16,713,40 msn, respectively; p=0.001), T wave (89+/-20,2 msn vs. 73,3+/-13,3 msn
      respectively, p=0.001), QT dispersion (26,8+/-17,5 msn vs. 13,5+/-20,4 msn
      respectively, p=0.002), JTcorrected (331,6+/-39,8%; vs. 350,1+/-39,7%
      respectively; p=0.01). Furthermore; Tpeak-Tend duration (89+/-20,2 msn vs. 73,3+/
      13,9 msn respectively; p=0.001), T wave (204+/-34,9 msn vs. 189,2+/-24,8 msn
      respectively; p=0.003), Tpeak-Tend/QT ratio (0,22+/-0,05 msn vs. 0,19+/-0,03 msn
      respectively, p=0.001) were significantly higher in patients compared to
      controls. Tpeak-Tend/QTc ratio was also significantly higher in the CSF group
      compared to the controls. (0,21+/-0,05 msn vs. 0,17+/-0,03 msn respectively, p
      =0.001). Conclusion: Ventricular repolarization parameters are prolonged in
      patients with CSF.

PMID- 28496927
TI  - E/Ea For The Prediction of Left Atrial Appendage Thrombi in Patients with Atrial
      Fibrillation and Severe Mitral Stenosis.
AB  - Atrial fibrillation (AF), left atrial appendage thrombi (LAAT) and subsequent
      embolic stroke are the most frequent complications of mitral stenosis .E/Ea is
      used traditionally for the assessment of left atrium pressure, and besides AF and
      dilated LA size which promotes stasis of blood in LA, high LA pressure also play
      a role to clot formation in LA .The receiver operator characteristics (ROC) curve
      point-coordinates identified an E:e' value of >= 36.5to have 57.14% sensitivity
      and 90.91% specificity for LAAT;We find this ratio relatively specific for
      prediction of LAAT, independent of MVA and LA volume, however it needs to be
      externally validated.

PMID- 28496928
TI  - Idiopathic Paroxysmal Atrio-Ventricular Block. What is The Mechanism?
AB  - Idiopathic paroxysmal atrioventricular (AV) block poses a true diagnostic
      challenge. What is clear about this entity is the confusion about its definition
      and consequently about its etiology. According to certain sources, the diagnosis
      of this block requires the lack of a structural cardiac pathology that justifies
      the observed manifestations and an absence of electrocardiographic disorders
      prior to an episode. The clinical presentation of idiopathic paroxysmal AV block
      does not differ from that of another cardiogenic syncope or of a vasovagal
      syncope with a significant cardioinhibitory component. With respect to the
      mechanism that explains this block, it has been postulated that patients with low
      basal adenosine levels exhibit hyperaffinity of the A2 receptors of the AV node.
      Variations in plasma adenosine levels may favor episodes of paroxysmal AV block.
      The diagnosis of this block is complex and can require years to determine.
      Routine electrophysiological examination of these patients is not cost effective
      due to the low sensitivity and specificity of this approach. Numerous groups have
      supported the use of an implantable loop recorder to substantiate AV block
      paroxysms and assess their clinical correlations. Permanent stimulation devices
      are utilized to reduce syncopal recurrence.

PMID- 28496930
TI  - Percutaneous Vacuum-Assisted Thrombectomy Device Used for Removal of Large
      Vegetations on Infected Pacemaker and Defibrillator Leads as an Adjunct to Lead
      Extraction.
AB  - This case series reports our early experience with a minimally invasive
      percutaneous method of safely removing large vegetations during lead extraction
      in septic cardiac implantable electronic devices (CIED). Debate exists concerning
      the management of vegetations involving these devices. Lead extraction is
      mandated for infections, but vegetations may embolize, causing complications.
      Surgical debridement is recommended; alternatives include cardiopulmonary bypass,
      minimally invasive thoracotomy, or transatrial approaches. The AngioVac device
      allows percutaneous right heart bypass and suction removal of vegetations under
      echocardiographic and fluoroscopic guidance. This case series describes our first
      20 patients, all critically ill with persistent sepsis and vegetations despite
      long-term antibiotics. This series includes patients who would not have been
      eligible for alternative procedures due to contraindications and highlights the
      potential role of this new technology.

PMID- 28496929
TI  - Management of Patients with Atrial Fibrillation: Focus on Treatment Options.
AB  - Atrial fibrillation (AF) is leading cardiac arrhythmia with important clinical
      implications. Its diagnosis is usually made on the basis on 12-lead ECG or 24
      hour Holter monitoring. More and more clinical evidence supports diagnostic use
      of cardiac event recorders and cardiovascular implantable electronic devices
      (CIED). Treatment options in patients with atrial fibrillation are extensive and
      are based on chosen rhythm and/or rate control strategy. The use and selected
      contraindications to AF related pharmacotherapy, including anticoagulants are
      shown. Nonpharmacological treatments, comorbidities and risk factors control
      remain mainstay in the treatment of patients with AF. Electrical cardioversion
      consists important choice in rhythm control strategy. Much progress has been made
      in the field of catheter ablation and cardiac surgery methods. Left atrial
      appendage occlusion/closure may be beneficial in patients with AF. CIED are used
      with clinical benefits in both, rhythm and rate control. Pacemakers, implantable
      cardioverter-defibrillators and cardiac resynchronization therapy devices with
      different pacing modes have guaranteed place in the treatment of patients with
      AF. On the other hand, the concepts of permanent leadless cardiac pacing, atrial
      dyssynchrony syndrome treatment and His-bundle or para-Hisian pacing have been
      proposed. This review summarizes and discusses current and novel treatment
      options in patients with atrial fibrillation.

PMID- 28496931
TI  - Safety of The Direct Oral Anticoagulant Edoxaban for Atrial Fibrillation After
      Cardiac Surgery: Pilot Study.
AB  - Direct oral anticoagulants have recently been recommended for non-valvular atrial
      fibrillation, but have rarely been studied in the field of cardiac surgery. We
      prospectively investigated the safety of edoxaban, a novel oral anticoagulant,
      for use in cardiac surgery patients with postoperative atrial fibrillation
      (POAF), which is the most common complication of cardiac surgery and can lead to
      stroke. The subjects were adult cardiac surgery patients with POAF who received
      oral edoxaban for 2 months in an open-label pilot study. The primary endpoint was
      cerebrovascular/bleeding events up to 2 months, while the secondary endpoints
      were hemoglobin, prothrombin time, and activated partial thromboplastin time.
      There were no cerebrovascular or bleeding events during edoxaban treatment and
      the test drug was not discontinued by any patient. There was no macroscopic
      hematuria and hemoglobin did not decrease, being significantly higher than the
      baseline level after 2 months. The prothrombin time was significantly prolonged
      from 1 week to 2 months and the activated partial thromboplastin time was
      significantly prolonged from 1 day to 2 months. Echocardiography detected
      pericardial effusion in 1 patient, but hemoglobin did not decrease and the
      effusion improved with diuretic therapy. In conclusion, despite the limited
      sample size of this pilot study, it was demonstrated that edoxaban does not
      induce bleeding in patients with POAF after cardiac surgery, suggesting that it
      is safe to perform a large-scale efficacy study of edoxaban as anticoagulant
      therapy for POAF.

PMID- 28496932
TI  - Mobitz Type 2 AV Block Dissolved With Contrast Injection.
AB  - There are many cases in the literature concerning the occurence of
      atrioventricular block in acute myocardial infarction. The prevelance and
      management of AV block in the setting of chronic myocardial ischemia remains
      unclear. Our case presented with stable angina pectoris. Treadmill test revealed
      Mobitz Type 2 AV block which disappeared with contrast injection and re-occured
      after injection during PCI.

PMID- 28496933
TI  - Internet Survey: Health Screening in Sports.
AB  - While cardiovascular screening protocols exist, they have been focused on
      teenaged and college aged athletes versus adult athletes. To assess community
      awareness of health screening as related to adult athletes, we have created an
      internet questionnaire (QN). The survey was posted through social media (e.g.
      Facebook, Reddit, Flotrack and Active), for 11 months, that queried sports
      history, medical history, and symptoms while playing sports. A total of 3,750
      respondents (R) answered the questionnaire, 2,776 male and 974 female. Age range:
      18-83 yrs, avg: 33.7+/-11.22 yrs, median: 31 yrs. Seventy four per cent of R
      (2,775/3,750) reported having at least one of the following symptoms while
      playing sports: dizziness, blacking/passing out, racing heartbeat, or chest pain,
      and 13.5% (505/3,750) of R reported two or more. 62.3% (1,730/2,775) did not
      recall having symptoms. This underreporting was a result of "no one asking" 49.5%
      (857/1,730); "not answering after being asked" 28.2% (488/1,730), and "not
      telling the truth" 22.2% (384/1,730). Of interest, 97.1% (3,642/3,750) want a
      screening QN; 95.8% (3,592/3,750) want pre-screening by an MD. Prior to sports,
      only 22.9% (857/3,750) were required to answer a QN vs 38.0% (1,424/3,750) had a
      physical exam (PE); 14.9% (560/3,750) of individuals had both PE and QN. We
      conclude that adult participants in sports commonly experience symptoms but do
      not report them. Nearly all respondents favor participating in a screening
      questionnaire that would assess for cardiovascular problems.

PMID- 28496934
TI  - Catheter Ablation for Persistent and Long-Standing Persistent Atrial
      Fibrillation.
AB  - Persistent and long-standing persistent atrial fibrillation evolves from complex
      arrhythmogenic substrate and sources. Multiple studies have shown improved
      freedom from arrhythmia recurrences if sinus rhythm had been restored during the
      index ablation; however, such harder procedural endpoint requires laborious
      stepwise approach almost invariably pursuing non-pulmonary-vein sources. Longer
      term conversion of persistent atrial fibrillation into sinus rhythm is associated
      with significant improvement in major indices of hemodynamic and functional
      status; these indices also represent major predictors of cardiovascular
      mortality. Optimal ablation techniques and strategies preserving most of the
      individual potential for functional improvement need to be established.

PMID- 28496935
TI  - Catheter Ablation of Incisional Atrial Tachycardia.
AB  - Tachycardias after atrial incisions represent frequent and serious problem. The
      majority of them are based on a re-entry electrical activation around a
      combination of anatomic and surgically created obstacles. Considering significant
      progress of cardiovascular surgery during the last decade along with potential
      large amount of open-heart procedures in the near future the number of incisional
      tachycardias has a tendency to increase. The aim of this work was to quantify the
      magnitude of the problem, characterize the tachycardias after different surgical
      operations and to analyze possible interventional treatment strategies. Nowadays
      evolution of mapping and ablation technologies may contribute to radically
      treatment of this type of arrhythmias while there are still a lot of issues that
      should be solved to improve the results of interventional treatment of incisional
      tachycardias.

PMID- 28496936
TI  - Strategies to Improve Safety and Efficacy of Atrial Fibrillation Ablation Using
      Electrode Multipolar Phased RF PVACTM Catheter: a Case Report.
AB  - Phased radiofrequency ablation with a single catheter technique, using a 9
      electrode circumferential catheter, is a viable approach to pulmonary vein
      isolation for the treatment of atrial fibrillation. However, creating effective
      transmural lesions with such technique, while avoiding serious complications like
      atrioesophageal fistula, can be difficult. This case illustrates a challenging
      scenario, where catheter maneuvers fail to allow safe radiofrequency delivery,
      due to esophageal temperature rise, despite extensive navigating maneuvers.
      Changing the bipolar-to-unipolar ratio of energy delivery, from 2:1 to 4:1,
      allowed the creation of effective lesions, avoiding excessive increase in
      esophageal temperature.

PMID- 28496937
TI  - Amiodarone-Induced Third Degree Atrioventricular Block and Extreme QT
      Prolongation Generating Torsade Des Pointes in Paroxysmal Atrial Fibrillation.
AB  - Amiodarone is still the most potent antiarrhythmic drug in the prevention of life
      threatening ventricular arrhythmias and demonstrates a very low incidence of
      torsade de pointes. An unusual case of an 81-year-old woman who developed serious
      abnormalities of the conduction system of the heart and torsade des pointes
      during intravenous infusion of amiodarone for the treatment of paroxysmal atrial
      fibrillation is described. To the best of our knowledge, this is the first case
      showing an association of intravenous amiodarone-induced third degree
      atrioventricular block and extreme QT interval prolongation generating torsade
      des pointes in a patient with paroxysmal atrial fibrillation who required an
      implantable cardioverter-defibrillator. Currently, amiodarone is still one of the
      few remaining treatment options for the medical therapeutic management of serious
      ventricular arrhythmias and to reduce the incidence of atrial fibrillation
      without increasing mortality or sudden cardiac death rates in heart failure
      patients like our elderly present patient. Nevertheless, we have to keep in mind
      that intravenous amiodarone may generate serious abnormalities of the conduction
      system of the heart and lethal ventricular arrhythmias in certain patients.

PMID- 28496939
TI  - Happy Holidays!!!

PMID- 28496938
TI  - Brugada Syndrome:Risk Stratification And Management.
AB  - The Brugada syndrome (BrS) is an arrhythmogenic disease associated with an
      increased risk of ventricular fibrillation and sudden cardiac death. The risk
      stratification and management of BrS patients, particularly of asymptomatic ones,
      still remains challenging. A previous history of aborted sudden cardiac death or
      arrhythmic syncope in the presence of spontaneous type 1 ECG pattern of BrS
      phenotype appear to be the most reliable predictors of future arrhythmic events.
      Several other ECG parameters have been proposed for risk stratification. Among
      these ECG markers, QRS-fragmentation appears very promising. Although the value
      of electrophysiological study still remains controversial, it appears to add
      important information on risk stratification, particularly when incorporated in
      multiparametric scores in combination with other known risk factors. The present
      review article provides an update on the pathophysiology, risk stratification and
      management of patients with BrS.

PMID- 28496940
TI  - Complete genome sequence of bacteriochlorophyll-synthesizing bacterium
      Porphyrobacter neustonensis DSM 9434.
AB  - The genus Porphyrobacter belongs to aerobic anoxygenic phototrophic bacteria
      cluster. Porphyrobacter neustonensis DSM 9434 was isolated from a eutrophic
      freshwater pond in Australia, and is able to synthesize Bacteriochlorophyll a as
      well as grow under aerobic conditions. It is the type species of the genus
      Porphyrobacter. Here we describe the characteristics of the strain DSM 9434,
      including the genome sequence and annotation, synthesis of BChl a, and metabolic
      pathways of the organism. The genome of strain DSM 9434 comprises 3,090,363 bp
      and contains 2,902 protein-coding genes, 47 tRNA genes and 6 rRNA genes. Strain
      DSM 9434 encodes 46 genes which participate in BChl a synthesis and this
      investigation shed light on the evolution and functional implications regarding
      bacteriochlorophyll synthesis.

PMID- 28496941
TI  - Chromosomal features of Escherichia coli serotype O2:K2, an avian pathogenic E.
      coli.
AB  - Escherichia coli causing infection outside the gastrointestinal system are
      referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a
      subgroup of extra-intestinal pathogenic E. coli and infections due to avian
      pathogenic E. coli have major impact on poultry production economy and welfare
      worldwide. An almost defining characteristic of avian pathogenic E. coli is the
      carriage of plasmids, which may encode virulence factors and antibiotic
      resistance determinates. For the same reason, plasmids of avian pathogenic E.
      coli have been intensively studied. However, genes encoded by the chromosome may
      also be important for disease manifestation and antimicrobial resistance. For the
      E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several
      studies, and E. coli APEC_O2 may therefore serve as a reference strain in future
      studies. Here we describe the chromosomal features of E. coli APEC_O2. E. coli
      APEC_O2 is a sequence type ST135, has a chromosome of 4,908,820 bp (plasmid
      removed), comprising 4672 protein-coding genes, 110 RNA genes, and 156
      pseudogenes, with an average G + C content of 50.69%. We identified 82 insertion
      sequences as well as 4672 protein coding sequences, 12 predicated genomic
      islands, three prophage-related sequences, and two clustered regularly
      interspaced short palindromic repeats regions on the chromosome, suggesting the
      possible occurrence of horizontal gene transfer in this strain. The wildtype
      strain of E. coli APEC_O2 is resistant towards multiple antimicrobials, however,
      no (complete) antibiotic resistance genes were present on the chromosome, but a
      number of genes associated with extra-intestinal disease were identified.
      Together, the information provided here on E. coli APEC_O2 will assist in future
      studies of avian pathogenic E. coli strains, in particular regarding strain of E.
      coli APEC_O2, and aid in the general understanding of the pathogenesis of avian
      pathogenic E. coli.

PMID- 28496942
TI  - TGF-beta1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.
AB  - BACKGROUND: Ninety percent of pancreatic cancer patients have less than 5-year
      overall survival and approximately 50% of cases were diagnosed with metastasis in
      the time of admission. Previous evidences have demonstrated the strong
      association between TGF-beta1 variations and cancer susceptibility so far.
      METHODS: A total of 78 patients with pancreatic cancer and 94 healthy controls
      were enrolled in this case- control study between 2007 and 2012. Genomic DNA was
      isolated from peripheral blood samples according to phenol chloroform extraction.
      The genotypes of TGF-beta1 rs rs1800469 and rs1800471 were determined using the
      polymerase chain reaction-restriction fragment length polymorphism method.
      RESULTS: The mean age of cases and the control group were 64.50 +/- 13.718 and
      40.12 +/- 16.001, respectively. For polymorphism -509 C>T, the frequency of TT
      genotype were 31 (33.0), CT, 47(50) and CC, 16 (17) in control and 19 (24.4), 45
      (57.7) and 14 (17.9) in cases respectively. In position +915 G>C, the frequency
      of GG genotype was 84 (89.4) and GC, 10 (10.6) in control and 71 (91.0) and 7 (9)
      in cases, respectively. We did not observe any significant differences in the
      genotype and allele frequencies of the TGF-beta1-509 C>T (rs1800469) and codon
      +915 G>C (rs1800471) between the two study groups (P>0.05). CONCLUSION: we found
      that TGF-beta1 gene polymorphisms rs1800469 and rs1800471 might not play a role
      in pancreatic cancer susceptibility in Iranian population.

PMID- 28496943
TI  - Research in Iran: An Overview.

PMID- 28496945
TI  - Gestational Exposure to Silymarin Increases Susceptibility of BALB/c Mice Fetuses
      to Apoptosis.
AB  - BACKGROUND: Silymarin is a flavonolignan that has been the subject of research to
      evaluate the beneficial properties for decades. Silymarin has been known for its
      potent cytoprotective, hepatoprotective and antioxidant activities. The goal of
      the present study was to gain a deeper understanding of possible molecular
      mechanisms of apoptosis of the injuries induced by silymarin on BALB/c mice
      fetuses. METHODS: The present experimental study was carried out in virgin female
      BALB/c mice. The animals were divided randomly into 4 groups. Three test groups
      were injected intraperitoneally with silymarin at doses of 50, 100 and 200
      mg/kg/day during gestational days 6-15. The control group received the solvent by
      the same route at equivalent volume. Western blot analysis was conducted to
      determine the levels of caspase-3 and caspase-8 in fetal heart, kidney, lungs and
      brain tissue. RESULTS: The results of this study showed that silymarin
      administration during organogenesis at doses of 50, 100 and 200 mg/kg can
      significantly increase the protein levels of caspase-3 and 8 in heart, kidneys
      and brain tissues of mice fetuses compared with control group (p<0.001).
      Silymarin exposure could not change the level of apoptotic markers in fetal lung
      tissue. CONCLUSION: According to the results, programmed cell death, especially
      via the intrinsic pathway, plays a pivotal role in the pathogenesis of silymarin
      induced malformations in some tissue including heart, kidneys and brain. More
      studies are needed to determine other molecular mechanisms underlying silymarin-
      induced embryo toxicity.

PMID- 28496944
TI  - Current State of Cartilage Tissue Engineering using Nanofibrous Scaffolds and
      Stem Cells.
AB  - Cartilage is an avascular, aneural, and alymphatic connective tissue with a
      limited capacity caused by low mitotic activity of its resident cells,
      chondrocytes. Natural repair of full thickness cartilage defects usually leads to
      the formation of fibrocartilage with lower function and mechanical force compared
      with the original hyaline cartilage and further deterioration can occur. Tissue
      engineering and regenerative medicine is a promising strategy to repair bone and
      articular cartilage defects and rehabilitate joint functions by focusing on the
      optimal combination of cells, material scaffolds, and signaling molecules. The
      unique physical and topographical properties of nanofibrous structures allow them
      to mimic the extracellular matrix of native cartilage, making an appropriate
      resemblance to induce cartilage tissue regeneration and reconstruction. To
      improve simulation of native cartilage, the incorporation of nanofibrous
      scaffolds with suitable corresponsive cells could be effective. In this review
      article, an attempt was made to present the current state of cartilage tissue
      engineering using nanofibrous scaffolds and stem cells as high proliferative
      immune privilege cells with chondrogenic differentiation ability. The
      comprehensive information was retrieved by search of relevant subject headings in
      Medline/Pubmed and Elsevier databases.

PMID- 28496946
TI  - Alpha Alumina Nanoparticle Conjugation to Cysteine Peptidase A and B: An
      Efficient Method for Autophagy Induction.
AB  - BACKGROUND: Autophagy as a cellular pathway facilitates several immune responses
      against infection. It also eliminates invading pathogens through transferring
      content between the cytosol and the lysosomal vesicles and contributes to the
      cross-presentation of exogenous antigens to T lymphocytes via MHC class I
      pathway. Autophagy induction is one of the main targets for new drugs and future
      vaccine formulations. Nanoparticles are one of the candidates for autophagy
      induction. Cysteine Peptidase A (CPA) and Cysteine Peptidase B (CPB) are two
      members of papain family (Clan CA, family C1) enzyme that have been considered as
      a virulence factor of Leishmania (L.) major, making them suitable vaccine
      candidates. In this research, Leishmania major cysteine peptidase A and B (CPA
      and CPB) conjugation to alpha alumina nanoparticle was the main focus and their
      entrance efficacy to macrophages was assessed. METHODS: For this purpose, CPA and
      CPB genes were cloned in expression vectors. Related proteins were extracted from
      transformed Escherichia coli (E. coli) and purified using Ni affinity column.
      Alpha alumina nanoparticles were conjugated to CPA/CPB proteins using
      Aldehyde/Hydrazine Reaction. Autophagy induction in macrophages was assessed
      using acridine orange staining. RESULTS: CPA/CPB protein loading to nanoparticles
      was confirmed by Fourier Transform Infrared Spectroscopy. alpha-alumina
      conjugated CPA/CPB antigen uptake by macrophages at different concentrations was
      confirmed using fluorescence microscope and flowcytometry. Highly efficient
      CPA/CPB protein loading to alpha-alumina nanoparticles and rapid internalization
      to macrophages introduced these nanocarriers as a delivery tool. Acridine orange
      staining demonstrated higher autophagy induction in CPA/CPB protein conjugated
      with alpha-alumina nanoparticles. CONCLUSION: alpha-alumina nanoparticles may be
      a promising adjuvant in the development of therapeutic leishmania vaccines
      through antigen delivery to intracellular compartments, induction of autophagy
      and cross presentation to CD8 lymphocytes.

PMID- 28496947
TI  - Efficient Media for High Lipase Production: One Variable at a Time Approach.
AB  - BACKGROUND: Lipase enzymes have applications in a wide range of industries. A
      crucial determining factor of industrial prices of these enzymes is the culture
      media composition that is constantly under review by researchers. In this work,
      for maximum lipase production by Bacillus sp. ZR-5, culture media compositions
      were optimized using "one variable at a time" strategy. METHODS: For this
      purpose, the culture medium parameters such as low and high cost carbon and
      nitrogen sources, substrates and incubation times were evaluated. RESULTS:
      Maximum lipase activity was achieved after 24 hr of incubation with 1.5% of
      glucose syrup (1600+/-69.1 u/mg), 1% of fish powder (1238+/-36.7 u/mg) and olive
      oil (1407+/-2.1 u/mg) as low cost carbon and nitrogen sources and substrate,
      respectively. CONCLUSION: Our results show a significant increase in lipase
      activity with usage of low cost sources; this could help in reducing the media
      prices for industrial application of lipase enzyme.

PMID- 28496948
TI  - Evaluation of IgY Antibody as a Polyspecific Coombs-Reagent.
AB  - BACKGROUND: During the last twenty years, the extraction of specific egg yolk
      (IgY) antibodies from the immunized chickens has been accepted as a useful
      alternative to the immunization of mammals. The aim of the present study was
      immunizing the chickens with Human Umbilical Cord Serum (HUCS) and the extraction
      of specific anti-human globulins (IgG, C3b, and C3d) antibodies from egg yolk in
      order to obtain polyspecific Coombs reagent. METHODS: The novelty of this work
      was the achievement of a polyclonal reagent through a very cheap alternative
      method in accordance with all ethical regulations required for obtaining it.
      Three Leghorn hens (21 weeks old) were immunized four times for a period of 66
      days with 20uL of HUCS mixed with PBS/FCA or FIA each time. The extraction of IgY
      antibodies was performed according to the method of lipid precipitation of yolk
      and using water soluble fraction as the reagent material. The resulting IgY
      antibody was characterized by SDS-PAGE and immunoelectrophoresis and tested for
      the presence of hetero-agglutinins by means of direct agglutination using human
      erythrocytes of all blood groups treated with 0.1% papain and for indirect Coombs
      test to evaluate its specificity to fractions (C3b, C3d, C4d) of human complement
      and human IgG, respectively. RESULTS: Our findings show, that, the reagent
      obtained contains IgY and other 3 proteins (SDS-PAGE), and reacts specifically
      with plasma proteins, that migrate in beta and Upsilon regions. In
      immunoelectrophoresis, in addition, there is the presence of low hetero
      agglutinins levels in IgY-preparation (3 lots), and the possibility to produce
      high amount (more than 500 ml/egg) of polyspecific Coombs-reagent in chickens is
      also discussed. CONCLUSION: IgY-preparation (3 lots), and the possibility to
      produce high amount (more than 500 ml/egg) of polyspecific Coombs-reagent in
      chickens with the originality to achieve a polyclonal reagent through a very
      cheap alternative method in accordance with all ethical regulations required for
      obtaining it, was also discussed.

PMID- 28496949
TI  - The Effect of Interactions of Single Nucleotide Polymorphisms of APOA1/APOC3 with
      Food Group Intakes on the Risk of Metabolic Syndrome.
AB  - BACKGROUND: The aim of this study was to examine the interaction of dietary food
      groups and genetic variants of APOA1/APOC3, relative to Metabolic Syndrome (MetS)
      risk in adults. METHODS: In this matched nested case-control study, 414 MetS
      subjects and 414 controls were selected from among participants of Tehran Lipid
      and Glucose Study. Dietary intake was assessed with the use of a valid and
      reliable semi-quantitative food frequency questionnaire. Single Nucleotide
      Polymorphisms (SNPs), APOA1 (rs670, -75G>A and rs5069, +83C>T/APOC3 rs5128
      C3238>G) were genotyped by the conventional polymerase chain reaction and
      restriction fragment length polymorphism. RESULTS: The mean (SD) of age was 40.7
      (13) and 41.2 (13) years in male cases and controls versus 44.0 (11) and 44.0
      (12) years in female case and controls. A significant interaction between intake
      quartiles of the sugar group and APOA1 combined group (GA+AA/CT+TT) SNPs was
      found; The ORs for these genotype carriers were (1, 0.44, 0.36, 0.23; P
      trend<0.001) in quartiles of intake, relative to other combined genotypes (P
      interaction=0.02). MetS risk appeared to be increased significantly in higher
      quartiles of sweet beverages and fish intakes in the GA+AA/CT+TT/CC genotypes of
      APOA1/APOC3 SNPs, compared to other genotypes (P interaction=0.01). The combined
      effect of genotypes of APOC3/APOA1 showed further decrease in MetS risk in higher
      quartiles of sugar group intakes (OR: 1, 0.24, 0.26, 0.14, P trend=0.001)
      relative to other combinations (P interaction=0.008). CONCLUSION: Results
      obtained demonstrate that some dietary food groups (sugar, fish, and sweet
      beverages) modulate the effect of APOA1/APOC3 SNPs in relation to MetS risk.

PMID- 28496950
TI  - Development of Flow Cytometry-Fluorescent In Situ Hybridization (Flow-FISH)
      Method for Detection of PML/RARa Chromosomal Translocation in Acute Promyelocytic
      Leukemia Cell Line.
AB  - BACKGROUND: Acute Promyelocytic Leukemia (APL) is a subclass of acute myeloid
      leukemia. The chromosomal aberration in 95% of APL cases is t(15; 17) (q22; q21),
      which prevents cell differentiation. Characterization of the underlying molecular
      lesion is valuable in determining optimal treatment strategy. The goal of this
      study was to develop a new and powerful Flow- FISH technique to detect the long
      isoform (L) of PML-RARa fusion transcript in NB4 cell line. METHODS: To achieve
      the best condition for fixation, two different fixatives including 2%
      paraformaldehyde and 75% ethanol were used. 0.2% Triton X-100 and 0.2% saponin
      were used for the permeabilization step .In hybridization, a wide range of times
      and temperatures were used and probe was designed in FRET system. Results were
      confirmed by fluorescent microscope assay and reverse transcription PCR. RESULTS:
      In the present study, a novel technique was successfully optimized that combines
      in situ hybridization with flow cytometry to detect the presence of PML-RARa
      transcript. Using standard fixation and permeabilization protocol of 2% PFA and
      0.2% saponin gave the best fluorescent results in flow cytometry. Also, results
      indicated that the optimum time and temperature for hybridization was 2 hr at 42
      degrees C. The results of reverse transcription PCR and fluorescent microscopy
      confirmed the presence of PML-RARa transcript. CONCLUSION: The concordance
      between the results of Flow-FISH and those of two other techniques including
      reverse transcription PCR and FISH indicated that this method would be applicable
      as a diagnostic test for APL in clinical samples and MRD monitoring.

PMID- 28496951
TI  - Can Aptameric Ligands Specific to Plasma Coagulation Factor VII Bind the
      Recombinant Form with High Affinity: Affinity Measurement by Fluorescence Method.
AB  - BACKGROUND: Among diverse protein purification systems, affinity chromatography
      is the most attractive one in the purification process of coagulation factors.
      Coagulation factor VII is a plasma serine protease that has a significant role in
      natural human hemostasis and its recombinant form such as AryoSevenTM, has been
      applied in clinical treatment of bleeding disorders. Immunoaffinity
      chromatography is the purification method of choice that is currently applied in
      the development of coagulation factor VIIa products. Aptamers as nucleic acid
      based affinity ligands are more promising than monoclonal antibodies. In
      addition, DNA aptamers are more acceptable than RNA ones in this regard. METHODS:
      In this study, two of the aptameric DNA oligonucleotides that showed acceptable
      affinities for purification of coagulation factor VIIa from plasma, were selected
      to evaluate their affinity against Aryoseven. A serial dilution of fluorescence
      labeled aptamers was incubated against the concentration of 1 nM from Aryoseven.
      Then, a fluorescence index was calculated according to the fluorescence intensity
      data measured from test and control samples. The dissociation constant of
      aptamers was calculated according to the fluorescence index using Prism5
      software. RESULTS: Results showed that the binding affinity of the 44 nucleotide
      aptamer was more than 81 nucleotide aptamer sequence. As a result, this aptamer
      could be optimized in order to develop aptamer based affinity chromatography
      process for this form of recombinant coagulation factor VIIa. DISCUSSION:
      Aptamers with shorter length of sequence could show higher affinity in target
      binding, as they could adapt more easily to suitable conformation according to
      target interaction. However, it should be considered that the selectivity of
      affinity ligands is also important for target purification and analytical
      applications.

PMID- 28496952
TI  - HIV Programs in Iran (Persia), Iraq and Saudi Arabia: A Brief Review of Current
      Evidence in West and Southwest Asia.
AB  - BACKGROUND: In Western and Southwest Asia, literature is not documented on human
      immunodeficiency virus (HIV) programs in Iran, Iraq and Saudi Arabia. The present
      study is the first brief review that describes HIV programs in these three
      neighboring countries. METHODS: Data regarding the evidence of HIV programs were
      gathered through a systematic literature searching. English publications were
      retrieved through searching online scientific databases. Grey literature was also
      searched online. The review was based on the studies related to the last decade.
      FINDINGS: Systematic searching resulted in retrieving 21,948 studies but only 21
      studies were relevant to the study aim. The review findings indicated that Iran
      has provided a nationwide sero-surveillance data system and has identified its
      key populations. Detecting HIV prevalence has been limited to case-finding in
      Iraq and Saudi Arabia. However, strategic plans for HIV have been provided in the
      three countries. HIV education, knowledge and support have been provided but
      still needs consideration in the three countries especially in Iraq. The low
      coverage of antiretroviral therapy (ART) has remained a critical gap in the
      provision of comprehensive HIV programs in these three countries. This issue has
      been followed by the lack of opiate substitution therapies for drug dependents
      and injecting drug users in Iraq and Saudi Arabia. Condom promotion and voluntary
      HIV counselling and testing have been provided for at-risk groups in the three
      countries but need more nationwide coverages. However, needle and syringe
      programs (NSPs) have been only provided in Iran. CONCLUSION: The review concluded
      that the provision of effective HIV programs should address training human
      resources and infrastructural development. This issue should be facilitated by
      international collaborations and governmental supports.

PMID- 28496953
TI  - Estrogen and Progesterone Replacement Therapy Prevent Methamphetamine-Induced
      Synaptic Plasticity Impairment in Ovariectomized Rats.
AB  - BACKGROUND: Methamphetamine (METH) is one of the most popular psychostimulants
      which produce long lasting learning and memory impairment. Previous studies have
      indicated that estrogen and progesterone replacement therapy attenuate cognitive
      impairment against a wide array of neurodegenerative diseases. Present study was
      designed to figure out the effects of estrogen, progesterone alone or in
      combination, on early long-term potentiation (E-LTP) at the cornu ammonis (CA1)
      area of the hippocampus in METH-exposed ovariectomized (OVX) rat. METHODS: Twenty
      one days after ovariectomy, the OVX rats received vehicle, estrogen [1 mg/kg,
      intraperitoneal (IP)] or progesterone (8 mg/kg, IP) and co-administration of
      estrogen plus progesterone during 14 consecutive days. On the 28th day, animals
      were exposed to neurotoxic METH regimens [four injections 6 mg/kg, subcutaneous
      (SC), 2 h intervals] 30 min after the hormones replacement. Finally, we
      investigated the effect of those ovarian hormones on synaptic plasticity using in
      vivo extracellular recording in the CA1 area of the hippocampus 2 days after last
      treatment. FINDINGS: The findings showed that the induction and maintenance phase
      of E-LTP was impaired in the METH exposed animals compared to the saline group.
      Data from this study demonstrated that treatment with estrogen and progesterone
      showed a significant facilitation for induction and enhancement of the
      maintenance of LTP in animals that received METH. In addition, co-administration
      of estrogen plus progesterone did not significantly affect the hippocampal
      synaptic plasticity in METH-exposed OVX rats in comparison with METH-exposed
      animals that received vehicle injections. CONCLUSION: The present findings
      provide new insight about treatment with ovarian hormones on synaptic plasticity
      deficits induced by METH.

PMID- 28496954
TI  - Sexual Risk Behaviors Constructed in Iranian Women's Life with Substance Use
      Disorders: A New Implication of Human Ecological Theory.
AB  - BACKGROUND: Drug abuse is one of the important variables influencing protective
      sexual behavior. The objective of this study was to explore how risky sexual
      behaviors develop in drug abusing women using human ecological theory. METHODS:
      In this study, we used a descriptive exploratory approach. The participants were
      32 drug abusing women from two of the selected drop-in centers (DICs) in south
      Tehran, Iran, where we could have access to a vast number of female drug users.
      Data was collected using semi-structured face-to-face interviews. Qualitative
      content analysis was used to analyze the data using Graneheim and Lundman
      procedure. FINDINGS: Risky sexual behavior in drug use disorders in women was
      found in four themes with thirteen emerged; sexual untaught at micro-system with
      two subthemes "unsafe home" and "drop out of school", Perception of differences
      at meso-system with three subthemes "lack of link between family and school",
      "doing manly behavior" and "low awareness of health puberty than peers",
      inappropriate marriages at exo-system with three subthemes "stigma", "fear of
      losing love relationship" and "self-devotion", marginalization at macro-system
      with four subthemes "barrier access to rights", "selling sex as a tool of
      security", "lack of belief as a sex worker" and "mistrust and doubt partner"
      using implication of human ecological theory. CONCLUSION: Findings suggest that
      strategies supporting the discovery of risky sexual behaviors in drug use
      disorders in women are important in order to provide counseling and education to
      form their decisions toward safety sex.

PMID- 28496955
TI  - Estimating the Size and Age-gender Distribution of Women's Active Social
      Networks.
AB  - BACKGROUND: Network Scale-up (NSU) method is an indirect method for the
      estimation of hidden behaviors. In NSU, respondents are asked about the number of
      members they know from a subpopulation of interest (e.g., injecting drug user)
      and assume that the prevalence of risky behavior in the networks of a random
      sample of respondents is similar to that of the population. However, first, we
      need to identify the total number of people each respondent knows [the social
      network size (C)]; Moreover, certain risky behaviors happen in particular age and
      gender groups. Our aim was to determine the size and age-gender distribution of
      female networks. METHODS: This cross-sectional study was conducted in the city of
      Kerman, Iran. A total sample of 1275 women was recruited using multistage
      sampling. In this study, 25 first names were selected as reference groups.
      Participants were asked how many people they know with the selected names. The
      respondent's answers were categorized into eight separate age-gender subgroups
      and C was estimated for each subgroup. FINDINGS: The results of this study showed
      that, on average, each Kermanian woman knows about 234 people and about two
      thirds of them are female (82 males and 152 females); moreover, participants were
      more likely to communicate with their peers. The majority of males (88%) known by
      Kermanian women were in young and middle age groups; in contrast the female young
      and middle age groups, who are at reproductive age, form only 45% of the female
      part of their networks. CONCLUSION: We have seen that the age-gender distribution
      of the networks is not the same as that of the general population. Our figures
      can be applied in NSU studies focusing on risky behaviors of particular age and
      gender groups.

PMID- 28496956
TI  - Effects of Opium Addiction and Cigarette Smoking on Hematological Parameters.
AB  - BACKGROUND: The aim of the present study was to investigate the effects of opium
      addiction and cigarette smoking on the complete blood count (CBC). METHODS:
      Eighty-six male subjects, including 31 opium-addicted cigarette smokers (OACS),
      19 opium-addicted non-cigarette smokers (OANCS), 17 non-opium-addicted cigarette
      smokers (NOACS), and 19 non-opium-addicted non-cigarette smokers (NOANCS)
      participated in this study. The CBC test was measured in all individuals.
      FINDINGS: The OACS had significantly higher white blood cell (WBC), lymphocyte,
      and red blood cell (RBC) count but lower in mean corpuscular volume (MCV)
      compared to NOANCS. The OANCS had significantly higher lymphocyte in comparison
      with NOACS. Our results demonstrated that the number of WBC, lymphocytes, and RBC
      were significantly higher, while, MCV was lower in OANCS subjects when compared
      to NOACS. The OACS had significantly higher level of lymphocyte in comparison
      with NOACS. The mean number of lymphocyte in OANCS was found significantly higher
      than NOACS. The smokers were shown to have significantly higher levels of WBC
      compared to NOANCS. CONCLUSION: Our results showed that opium-addiction,
      especially when associated with cigarette smoking, has intensive effects on
      hematological factors and these alteration might leads to greater risk for
      developing atherosclerosis, cardiovascular diseases, and imbalance in immune
      system.

PMID- 28496957
TI  - Injecting and Sexual Networks and Sociodemographic Factors and Dual HIV Risk
      among People Who Inject Drugs: A Cross-sectional Study in Kermanshah Province,
      Iran.
AB  - BACKGROUND: Few studies suggest that social network factors, including size of
      sexual network may associate with drug-related and sexual high-risk behaviors.
      The objective of this study is to investigate injecting and sexual networks and
      sociodemographic factors that might be associated with dual HIV risk (DHR) among
      people who inject drug (PWID). METHODS: The data from a cross-sectional study of
      455 PWID that were recruited through peer-referral sampling were used in this
      study. The data were collected using a structured questionnaire consisted of
      modules on sociodemographic characteristics, sexual and injection-related risk
      behaviors during 12 months before the interview. DHR was defined as engaged in
      both using a syringe previously used by other PWIDs and unprotected sex during
      last 12 months. Data analysis was performed with descriptive and logistic
      regression. In final model, we considered variables with P < 0.500 as
      statistically significant. Finally, reported adjusted odds ratio (AOR) and
      confidence interval (95% CI) for variables that were significant in the final
      model. FINDINGS: A total of 455 men who injected drugs participated in this
      study. The mean age +/- standard deviation (SD) was 33.2 +/- 7.3 (range 19-58)
      years. Overall, the prevalence of DHR In the last 12 months, 38% (95% CI: 18.3
      51.2%). Multivariate model showed that regular visit to needle, syringe programs
      (NSPs) reduced odd of HDR to 50% when adjusted for other covariates, but still
      remained statistically significant (P < 0.050). The odds of reporting DHR was
      significantly higher in those >= 2 sex partners and injection partner (P <
      0.010). Odds of DHR was higher (AOR: 2.3) among participants who had more than 2
      injection per day but was not statistically significant (P > 0.050). CONCLUSION:
      DHR was common in PWID in Kermanshah, Iran. Having multiple injecting and sexual
      partners increased the odds of engaging in dual risk behaviors, but regular visit
      of NSPs can reduce the DHR among PWID.

PMID- 28496958
TI  - Prevalence of HIV/AIDS among Iranian Prisoners: A Review Article.
AB  - BACKGROUND: Worldwide, prisoners are more at risk of being infected by human
      immunodeficiency virus (HIV) as well as hepatitis C and B in comparison with
      other risk groups. The combination of acquired immune deficiency syndrome (AIDS),
      addiction and prison are factors that threaten the health of our society.
      Influence of risky behaviors is so common on transmission of AIDS into prisoners'
      bodies. This study used available information and reports to investigate the
      prevalence of HIV in Iranian prisons. METHODS: The following review of documents
      available in national and foreign databases, a total of 26 studies were
      investigated and required information was extracted from both the full papers and
      abstracts. FINDINGS: The selected studies differed methodologically in their
      sampling method and data collection tools. Within the 26 studies analyzed, there
      was a combined study cohort of 39707 people in whom HIV prevalence varied between
      0% and 24.40%. CONCLUSION: In this study, HIV prevalence ranged widely among the
      prisoners, and in most of these studies, the rate in Iran was higher than that of
      other countries. The prevalence of disease was highest among intravenous drug
      users. Unless proper preventive and control plans among risk groups such as
      prisoners are not implemented in a timely and suitable manner, the risk of
      infection in the broader society will increase.

PMID- 28496959
TI  - Is Pathological Trading an Overlooked Form of Addiction?

PMID- 28496960
TI  - Erratum: Willingness to Receive Treatment for Hepatitis C among Injecting Drug
      Users on Methadone Program: Implications for Education and Treatment.
AB  - [This corrects the article on p. 90 in vol. 2.].

PMID- 28496961
TI  - Mobilization, Isolation and Characterization of Stem Cells from Peripheral Blood:
      a Systematic Review.
AB  - OBJECTIVES: The purpose of this article is to systematically review the methods
      of mobilization, isolation and characterization of stem cells from peripheral
      blood and to discuss their potential therapeutic applications for bone tissue
      regeneration. MATERIAL AND METHODS: An electronic literature search was performed
      through MEDLINE (PubMed) electronic database. The search was restricted to
      English language articles published during the last 10 years, from January 2006
      to November 2016. RESULTS: In total, 37 literature sources were reviewed, and 11
      of the most relevant articles that are suitable to the criteria were selected.
      Articles were analysed with data on animals and humans for mobilization,
      isolation and characterization of stem cells from peripheral blood. From the
      examination of selected articles, the mobilization materials, side effects,
      alternatives and factors affecting the extracted amount of mesenchymal stem cells
      (MSC) from mobilized peripheral blood of healthy individuals, as well as
      characterization of mobilized MSC were reviewed in this article. CONCLUSIONS:
      Bone tissue engineering is a potential alternative strategy in bone regeneration
      and bone defect repair, however, insufficiency data display in the literature on
      potential therapeutic applications of peripheral blood stem cells for bone tissue
      regeneration.

PMID- 28496962
TI  - Scalloped Implant-Abutment Connection Compared to Conventional Flat Implant
      Abutment Connection: a Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: The objective was to test the hypothesis of no difference in implant
      treatment outcome after installation of implants with a scalloped implant
      abutment connection compared to a flat implant-abutment connection. MATERIAL AND
      METHODS: A MEDLINE (PubMed), Embase and Cochrane library search in combination
      with a hand-search of relevant journals was conducted. No language or year of
      publication restriction was applied. RESULTS: The search provided 298 titles.
      Three studies fulfilled the inclusion criteria. The included studies were
      characterized by low or moderate risk of bias. Survival of suprastructures has
      never been compared within the same study. High implant survival rate was
      reported in all the included studies. Significantly more peri-implant marginal
      bone loss, higher probing depth score, bleeding score and gingival score was
      observed around implants with a scalloped implant-abutment connection. There were
      no significant differences between the two treatment modalities regarding
      professional or patient-reported outcome measures. Meta-analysis disclosed a mean
      difference of peri-implant marginal bone loss of 1.56 mm (confidence interval:
      0.87 to 2.25), indicating significant more bone loss around implants with a
      scalloped implant-abutment connection. CONCLUSIONS: A scalloped implant-abutment
      connection seems to be associated with higher peri-implant marginal bone loss
      compared to a flat implant-abutment connection. Therefore, the hypothesis of the
      present systematic review must be rejected. However, further long-term randomized
      controlled trials assessing implant treatment outcome with the two treatment
      modalities are needed before definite conclusions can be provided about the
      beneficial use of implants with a scalloped implant-abutment connection on
      preservation of the peri-implant marginal bone level.

PMID- 28496963
TI  - In Vitro Comparison of Biological Effects of Coe-Pak and Reso-Pac Periodontal
      Dressings.
AB  - OBJECTIVES: The purpose of the present study was to compare the cytotoxicity of
      Reso-Pac and Coe-Pak periodontal dressing. MATERIAL AND METHODS: According to ISO
      10993-12:2012, 1-, 3- and 7-day extracts of the two periodontal dressings were
      prepared in cell culture medium and exposed to the two cultured cell lines. Cell
      viability and proliferation at 24 h and 72 h following exposure were evaluated
      using quantitative MTT assay. RESULTS: The results showed a significant (P <
      0.05) reduction in the viability of cells exposed to the 3- and 7-day Coe-Pak
      extracts at 24 h and 72 h compared to the control group (no exposure to the
      extract). Reso-Pac extracts slightly decreased cell viability compared to the
      control group. Understudy materials showed greater cytotoxicity against human
      osteoblast-like compared to the human gingival fibroblast cells. No significant
      (P > 0.05) difference was found in the viability of cells exposed to undiluted
      (100%) one-day extract and diluted (50%) extract of both understudy materials at
      24 h and 72 h after exposure. CONCLUSIONS: Based on the results, Reso-Pac
      periodontal dressing has less cytotoxicity than Coe-Pak.

PMID- 28496964
TI  - Oral Health Status of Institutionalized Individuals with Intellectual
      Disabilities in Lebanon.
AB  - OBJECTIVES: To assess the dental status of institutionalized intellectually
      disabled individuals in Lebanon and the role of background and behavioural
      determinants. MATERIAL AND METHODS: Oral health was recorded for 652 individuals
      (6, 12, 15 and 35 - 44 years old) using the decayed, missing and filled
      teeth/decayed and filled teeth (DMFT/dft) index. Data collected was statistically
      analysed with statistical significance set at P = 0.05. RESULTS: Overall, mean
      DMFT index score was 5.86 (SD 6); composed of 3.64 (SD 4.05) decayed (D) teeth;
      1.71 (SD 4.38) missing (M) teeth; 0.87 (SD 2.51) filled (F) teeth. DMFT was
      highest in adults (12.71 [SD 7.43]) and had a large component of missing (6.24
      [SD 7.02]) and filled (3.31 [SD 4.56]) teeth. DMFT scores ranged between 3.5 (SD
      4.44) at 6 years and 4.8 (SD 4.52) at 15 years and the decayed component was the
      main contributor. In multivariate analyses, governorate of residence was
      statistically significantly (P <= 0.040 and P <= 0.044) associated with D and
      DMFT, the degree of disability and caretaker educational level were statistically
      significantly (P = 0.009 and P = 0.008) associated with D, oral hygiene practices
      were statistically significantly (P <= 0.017; P < 0.001; P <= 0.017; P < 0.001)
      associated with D, M, F and DMFT and sugar consumption was statistically
      significantly (P <= 0.03 and P <= 0.019) associated with D and DMFT. CONCLUSIONS:
      In Lebanon, preventive and treatment programs to improve the oral health status
      of institutionalized intellectually disabled subjects are needed.

PMID- 28496965
TI  - MALT Lymphoma of Minor Salivary Glands in a Sjogren's Syndrome Patient: a Case
      Report and Review of Literature.
AB  - BACKGROUND: Sjogren's syndrome is a chronic systemic disease, characterized by
      lymphocytic infiltration and destruction mainly of the salivary and lacrimal
      glands, resulting in xerostomia and xeropthalmia. Sjogren's syndrome patients
      have a 44-fold excess risk for the development of non-Hodgkin's lymphoma
      particularly mucosa-associated lymphoid tissue (MALT) lymphoma, prevalently
      affecting the major salivary glands. In this report, a rare case of MALT lymphoma
      of minor salivary glands in a patient with Sjogren's syndrome is described. A
      review of the published cases of MALT lymphoma located in the minor salivary
      glands of patients with Sjogren's syndrome is provided. METHODS: In a 64-year-old
      female patient previously diagnosed with Sjogren's syndrome, an asymptomatic soft
      tissue mass at the palate was noticed, exhibiting rapid enlargement within one
      month. With a main differential diagnosis of salivary gland neoplasm or
      lymphoproliferative lesion, a partial biopsy was performed accompanied by proper
      immunohistochemical analysis. RESULTS: A final diagnosis of MALT lymphoma was
      rendered and the patient was referred for further multidisciplinary evaluation.
      Gastric endoscopy and biopsy revealed a Helicobacter pylori-negative gastric MALT
      lymphoma, while spleen involvement and bone marrow infiltration were also
      identified. Patient was classified as having stage IV disseminated disease and a
      standard chemotherapy protocol was administered; the treatment was well tolerated
      and resulted in complete remission. CONCLUSIONS: This case emphasizes the need
      for close monitoring of patients with Sjogren's syndrome by oral medicine
      specialists, which, besides ensuring proper management of xerostomia and its
      sequelae, may also lead to early recognition of lymphoma development.

PMID- 28496966
TI  - Effects of deer on the photosynthetic performance of invasive and native forest
      herbs.
AB  - Overabundant generalist herbivores can facilitate non-native plant invasions,
      presumably through direct and indirect modifications to the environment that
      affect plant performance. However, ecophysiological mechanisms behind ungulate
      mediated plant invasions have not been well-studied. At a long-term Odocoileus
      virginianus (white-tailed deer) exclusion site in a temperate deciduous forest,
      we quantified deer-mediated ecophysiological impacts on an invasive biennial
      Alliaria petiolata (garlic mustard) and two palatable native herbaceous
      perennials, Maianthemum racemosum and Trillium grandiflorum. In mid-summer, we
      found that leaf-level light availability was higher in unfenced areas compared
      with areas fenced to exclude deer. Alliaria in unfenced areas exhibited 50 %
      higher mean maximum photosynthetic rates compared with fenced areas. Further,
      specific leaf area decreased by 48 % on average in unfenced areas, suggesting
      leaf structural responses to higher light levels. Similarly, Maianthemum had 42 %
      higher mean photosynthetic rates and 33 % decreased mean specific leaf area in
      unfenced areas, but these functional advantages were likely countered by high
      rates of deer herbivory. By contrast, Trillium exhibited significantly lower (26
      %) maximum photosynthetic rates in unfenced areas, but SLA did not differ. Deer
      mediated differences in light saturated photosynthetic rates for all three
      species were only significant during months with overstory tree canopy cover,
      when light availability in the herb layer was significantly lower in fenced
      areas. Alliaria's enhanced photosynthetic rates implicate overabundant deer, a
      situation that is nearly ubiquitous across its invaded range. Collectively, our
      results provide empirical evidence that generalist herbivores can alter non
      native plant physiology to facilitate invasion.

PMID- 28496967
TI  - Synthesis and properties of lysosome-specific photoactivatable probes for live
      cell imaging.
AB  - Fluorescent dyes have become increasingly important in cell biology since they
      enable high signal-to-noise and selectivity in visualizing subcellular
      organelles. Photoactivatable dyes allow for tracking and monitoring of a subset
      of cells or organelles. Here, we report the synthesis and application of a new
      class of large Stokes shift fluorescent dyes that are water-soluble, cell
      permeable, non-cytotoxic, and lysosome-specific. Additionally, we demonstrate
      temporally controlled sequential photoactivation of individual cells in close
      spatial proximity.

PMID- 28496968
TI  - Resolving shortages of prescription drugs: the case for public-private
      collaboration.
AB  - The recent IJHPR article by Schwartzberg and colleagues presents new data on the
      growing problem of prescription drug shortages. Resolving shortages typically
      involves many participants: government, industry, physicians and healthcare
      facilities. Israel has a strong record of informal collaboration that can fix
      drug shortages quickly. The success of Israel's informal collaborations, as well
      as its formal partnerships, deserves broader recognition at home and more
      attention from the international community.

PMID- 28496969
TI  - Synthetic approaches to nucleopeptides containing all four nucleobases, and
      nucleic acid-binding studies on a mixed-sequence nucleo-oligolysine.
AB  - In this article we describe two solid-phase synthetic routes to obtain a nucleo
      oligolysine alpha-peptide containing all four natural nucleobases. The first one
      is based on the oligomerization of the nucleobase-containing monomers, easily
      synthesized as herein described. The second strategy has the advantage of
      avoiding the solution synthesis of the monomeric building blocks, leading to the
      final nucleopeptide by direct solid-phase couplings of the suitably protected
      nucleobases with the free amino groups on the growing peptide chain still
      anchored to the resin. Both strategies are general and can be applied to the
      synthesis of nucleopeptides having backbones formed by any other diamino acid
      moiety decorated with the four nucleobases. We also report the CD and UV studies
      on the hybridization properties of the obtained nucleopeptide, containing all
      four nucleobases on alternate lysines in the sequence, towards complementary DNA
      and RNA strands. The nucleo-oligolysine with a mixed-base sequence did not prove
      to bind complementary DNA, but was able to recognize the complementary RNA
      forming a complex with a higher melting temperature than that of the
      corresponding RNA/RNA natural duplex and comparable with that of the analogous
      PNA/RNA system.

PMID- 28496970
TI  - Electrical behaviour of native cellulose nanofibril/carbon nanotube hybrid
      aerogels under cyclic compression.
AB  - Hybrid aerogels consisting of cellulose nanofibers (CNF) and modified few-walled
      carbon nanotubes (FWCNT) are investigated under cyclic mechanical compression to
      explore "electrical fatigue". For this purpose the FWCNTs were hydrophilized,
      thus promoting their aqueous dispersibility to allow FWCNT/CNF hybrid hydrogels,
      followed by freeze-drying to obtain hybrid aerogels. The optimized composition
      consisting of FWCNT/CNF 20/80 wt/wt showed conductivity of 10-5 S cm-1 as
      promoted due to double percolation, and showed only small changes in electrical
      and mechanical behaviour upon cycling 100 times. The electrical behaviour under
      cycled compression shows good stability and reversibility.

PMID- 28496971
TI  - Paramagnetic relaxation enhancement for protein-observed 19F NMR as an enabling
      approach for efficient fragment screening.
AB  - Protein-observed 19F (PrOF) NMR is an emerging tool for ligand discovery. To
      optimize the efficiency of PrOF NMR experiments, paramagnetic relaxation
      enhancement through the addition of chelated Ni(II) was used to shorten
      longitudinal relaxation time without causing significant line broadening. Thus
      enhancing relaxation time leads to shorter experiments without perturbing the
      binding of low- or high-affinity ligands. This method allows for time-efficient
      screening of potential ligands for a wide variety of proteins in the growing
      field of fragment-based ligand discovery.

PMID- 28496972
TI  - VUV/UV light inducing accelerated phenol degradation with a low electric input.
AB  - This study presents the first evidence for the accelerated degradation of phenol
      by Fenton's reagent in a mini-fluidic VUV/UV photoreaction system (MVPS). A low
      pressure mercury lamp used in the MVPS led to a complete degradation of phenol
      within 4-6 min. The HO and HO2 originating from both Fenton's reagent and VUV
      photolysis of water were identified with suitable radical scavengers. The effects
      of initial concentrations of phenol, H2O2 and Fe3+ as well as solution pH on
      phenol degradation kinetics were examined. Increasing the initial phenol
      concentration slowed down the phenol degradation, whereas increasing the initial
      H2O2 or Fe3+ concentration accelerated the phenol degradation. The optimal
      solution pH was 3.7. At both 254 and 185 nm, increasing phenol concentration
      enhanced its absorption for the incident photons. The reaction mechanism for the
      degradation of phenol was suggested consistent with the results obtained. This
      study indicates that the VUV/UV photo-Fenton process has potential applications
      in the treatment of industrial wastewater containing phenol and related aromatic
      pollutants.

PMID- 28496973
TI  - 8-Styryl-substituted coralyne derivatives as DNA binding fluorescent probes.
AB  - Six new 8-styryl-substituted coralyne derivatives 4a-f were synthesized from
      coralyne (2) by a base catalysed Knoevenagel type reaction. It was shown by
      photometric and fluorimetric titrations of double stranded and quadruplex DNA to
      4b-d as well as by fluorimetric DNA denaturation experiments that these ligands
      bind to DNA with different binding modes at varying ligand-DNA ratios (LDR).
      Specifically, the addition of DNA caused initially a hypochromic effect in
      absorbance and, at a particular LDR, the development of a new red shifted
      absorption band with a hyperchromic effect. Furthermore, 4b-d induced a
      significant and selective stabilization of quadruplex DNA towards unfolding
      (DeltaTm = 31.6-32.9  degrees C at LDR = 5), which is even more pronounced as
      compared to the parent compound coralyne (2). Most notably, the addition of DNA
      to the dimethylamino-substituted derivative 4b leads to a new, strongly red
      shifted emission band at 695 nm. Hence, this derivative is a fluorescent probe
      that changes its fluorescence colour from green to red in the presence of DNA and
      even allows the fluorimetric analysis of living cells by staining of the
      nucleoli.

PMID- 28496974
TI  - Computational analysis of the solvation of coffee ingredients in aqueous ionic
      liquid mixtures.
AB  - In this paper, we investigate the solvation of coffee ingredients including
      caffeine, gallic acid as representative for phenolic compounds and quercetin as
      representative for flavonoids in aqueous mixtures of the ionic liquid 1-ethyl-3
      methylimidazolium acetate [C2mim][OAc] at various concentrations. Due to the
      anisotropy of the solutes we show that classical Kirkwood-Buff theory is not
      appropriate to study solvation effects with increasing ionic liquid content.
      However, excess coordination numbers as well as the mean residence time of
      solvent molecules at the surface of the solutes can be determined by Voronoi
      tessellation. Since the volume of the hydration shells is also available by this
      method, solvation free energies will be discussed as a function of the ionic
      liquid concentration to yield a physical meaningful picture of solvation for the
      anisotropic solutes. Hydrogen bonding capabilities of the solutes and their
      relevance for experimental extraction yields from spent coffee grounds are also
      discussed.

PMID- 28496975
TI  - Convergent synthesis and optical properties of near-infrared emitting
      bioluminescent infra-luciferins.
AB  - Infra-luciferin, an alkene linked analogue of luciferin, gives bioluminescence
      emission >700 nm and has the potential to be used for multiparametric in vivo
      imaging. We report here a high yielding, scalable and convergent synthesis of
      infra-luciferin which will allow the synthesis of other conjugated luciferins for
      investigation in near-infrared bioluminescence imaging. We demonstrated this
      potential by using the new route to synthesise a diene linked analogue of
      luciferin, the fluorescent and bioluminescent properties of which were compared
      to those of d-luciferin and infra-luciferin. We found that extension of
      conjugation to a diene linker resulted in the specific bioluminescence activity
      being reduced by 3-4 orders of magnitude compared to d-luciferin. Analogous to
      its fluorescence emission spectrum, the diene linked analogue exhibited two peaks
      in its bioluminescence spectrum, the major one being slightly blue-shifted
      compared to natural d-luciferin, and a minor peak at ca. 800 nm. The fluorescence
      quantum yield and pH dependence of fluorescence were also determined.

PMID- 28496976
TI  - Membrane properties and anti-bacterial/anti-biofouling activity of polysulfone
      graphene oxide composite membranes phase inversed in graphene oxide non-solvent.
AB  - A new and facile method for the fabrication of polysulfone-graphene oxide
      composite membranes is reported, where after casting, phase inversion is carried
      out with graphene oxide flakes (GO) in a coagulation bath. The membranes were
      characterized and the morphology was analysed using scanning electron microscopy.
      A bacterial inhibition ratio of 74.5% was observed with membranes fabricated from
      a very low concentration of di-water-GO non-solvent (0.048% of GO). The membranes
      were successfully tested for permeate flux and fouling resistance using activated
      sludge filtration from an MBR system. The observed trend shows that GO can
      operate as a protective barrier for membrane pores against the bacterial
      community. To our knowledge this is the first time where the immersion
      precipitation mechanism was carried out in a coagulation bath with GO flakes
      under continuous stirring. Using this method, a very low concentration of GO is
      required to fabricate membranes with conventional GO composite membrane
      properties and better selectivity.

PMID- 28496978
TI  - Erratum: Evolutionary Medicine: Why do humans get bunions?
AB  - [This corrects the article DOI: 10.1093/emph/eox001.].

PMID- 28496977
TI  - A generalized quantitative antibody homeostasis model: antigen saturation,
      natural antibodies and a quantitative antibody network.
AB  - In a pair of articles, we present a generalized quantitative model for the
      homeostatic function of clonal humoral immune system. In this second paper, we
      describe how antibody production controls the saturation of antigens and the
      network of antibody interactions that emerges in the epitome space with the
      establishment of the immune system. Efficient control of antigens, be it self or
      foreign, requires the maintenance of antibody concentrations that saturate
      antigen to relevant levels. Simple calculations suggest that the observed diverse
      recognition of antigens by natural antibodies is only possible by cross
      reactivity whereby particular clones of antibodies bind to diverse targets and
      shared recognition of particular antigens by multiple antibody clones contribute
      to the maintenance of antigen control. We also argue that natural antibodies are
      none else than the result of thymus-independent responses against immunological
      self. We interpret and explain antibody production and function in a virtual
      molecular interaction space and as a network of interactions. Indeed, the general
      quantitative (GQM) model we propose is in agreement with earlier models, confirms
      some assumptions and presumably provides the theoretical basis for the
      construction of a real antibody network using the sequence and interaction
      database data.

PMID- 28496979
TI  - Crystal structure and thermoelectric properties of Sr-Mo substituted CaMnO3: a
      combined experimental and computational study.
AB  - A combination of experimental and computational techniques has been employed to
      study doping effects in perovskite CaMnO3. High quality Sr-Mo co-substituted
      CaMnO3 ceramics were prepared by the conventional mixed oxide route.
      Crystallographic data from X-ray and electron diffraction showed an orthorhombic
      to tetragonal symmetry change on increasing the Sr content, suggesting that Sr
      widens the transition temperature in CaMnO3 preventing phase transformation
      cracking on cooling after sintering, enabling the fabrication of high density
      ceramics. Atomically resolved imaging and analysis showed a random distribution
      of Sr in the A-site of the perovskite structure and revealed a boundary structure
      of 90 degrees  rotational twin boundaries across {101}orthorhombic; the latter
      are predominant phonon scattering sources to lower the thermal conductivity as
      suggested by molecular dynamics calculations. The effect of doping on the
      thermoelectric properties was evaluated. Increasing Sr substitution reduces the
      Seebeck coefficient but the power factor remains high due to improved
      densification by Sr substitution. Mo doping generates additional charge carriers
      due to the presence of Mn3+ in the Mn4+ matrix, reducing electrical resistivity.
      The major impact of Sr on thermoelectric behaviour is the reduction of the
      thermal conductivity as shown experimentally and by modelling. Strontium
      containing ceramics showed thermoelectric figure of merit (ZT) values higher than
      0.1 at temperatures above 850 K. Ca0.7Sr0.3Mn0.96Mo0.04O3 ceramics exhibit
      enhanced properties with S1000K = -180 MUV K-1, rho1000K = 5 * 10-5 Omegam,
      k1000K = 1.8 W m-1 K-1 and ZT ~ 0.11 at 1000 K.

PMID- 28496980
TI  - Silver-induced reconstruction of an adeninate-based metal-organic framework for
      encapsulation of luminescent adenine-stabilized silver clusters.
AB  - Bright luminescent silver-adenine species were successfully stabilized in the
      pores of the MOF-69A (zinc biphenyldicarboxylate) metal-organic framework,
      starting from the intrinsically blue luminescent bio-MOF-1 (zinc adeninate 4,4'
      biphenyldicarboxylate). Bio-MOF-1 is transformed to the MOF-69A framework by
      selectively leaching structural adenine linkers from the original framework using
      silver nitrate solutions in aqueous ethanol. Simultaneously, bright blue-green
      luminescent silver-adenine clusters are formed inside the pores of the
      recrystallized MOF-69A matrix in high local concentrations. The structural
      transition and concurrent changes in optical properties were characterized using
      a range of structural, physicochemical and spectroscopic techniques (steady-state
      and time-resolved luminescence, quantum yield determination, fluorescence
      microscopy). The presented results open new avenues for exploring the use of MOFs
      containing luminescent silver clusters for solid-state lighting and sensor
      applications.

PMID- 28496981
TI  - Electron injection and scaffold effects in perovskite solar cells.
AB  - In spite of the impressive efficiencies reported for perovskite solar cells
      (PSCs), key aspects of their working principles, such as electron injection at
      the contacts or the suitability of the utilization of a specific scaffold layer,
      are not yet fully understood. Increasingly complex scaffolds attained by the
      sequential deposition of TiO2 and SiO2 mesoporous layers onto transparent
      conducting substrates are used to perform a systematic characterization of both
      the injection process at the electron selective contact and the scaffold effect
      in PSCs. By forcing multiple electron injection processes at a controlled
      sequence of perovskite-TiO2 interfaces before extraction, interfacial injection
      effects are magnified and hence characterized in detail. An anomalous injection
      behavior is observed, the fingerprint of which is the presence of significant
      inductive loops in the impedance spectra with a magnitude that correlates with
      the number of interfaces in the scaffold. Analysis of the resistive and
      capacitive behavior of the impedance spectra indicates that the scaffolds could
      hinder ion migration, with positive consequences such as lowering the
      recombination rate and implications for the current-potential curve hysteresis.
      Our results suggest that an appropriate balance between these advantageous
      effects and the unavoidable charge transport resistive losses introduced by the
      scaffolds will help in the optimization of PSC performance.

PMID- 28496982
TI  - Blood gases, biochemistry and haematology of Galapagos hawksbill turtles
      (Eretmochelys imbricata).
AB  - The hawksbill turtle, Eretmochelys imbricata, is a marine chelonian with a circum
      global distribution, but the species is critically endangered and has nearly
      vanished from the eastern Pacific. Although reference blood parameter intervals
      have been published for many chelonian species and populations, including nesting
      Atlantic hawksbills, no such baseline biochemical and blood gas values have been
      reported for wild Pacific hawksbill turtles. Blood samples were drawn from eight
      hawksbill turtles captured in near shore foraging locations within the Galapagos
      archipelago over a period of four sequential years; three of these turtles were
      recaptured and sampled on multiple occasions. Of the eight sea turtles sampled,
      five were immature and of unknown sex, and the other three were females. A
      portable blood analyzer was used to obtain near immediate field results for a
      suite of blood gas and chemistry parameters. Values affected by temperature were
      corrected in two ways: (i) with standard formulas and (ii) with auto-corrections
      made by the portable analyzer. A bench top blood chemistry analyzer was used to
      measure a series of biochemistry parameters from plasma. Standard laboratory
      haematology techniques were employed for red and white blood cell counts and to
      determine haematocrit manually, which was compared to the haematocrit values
      generated by the portable analyzer. The values reported in this study provide
      reference data that may be useful in comparisons among populations and in
      detecting changes in health status among Galapagos sea turtles. The findings
      might also be helpful in future efforts to demonstrate associations between
      specific biochemical parameters and disease or environmental disasters.

PMID- 28496983
TI  - Correlated velocity models as a fundamental unit of animal movement: synthesis
      and applications.
AB  - BACKGROUND: Continuous time movement models resolve many of the problems with
      scaling, sampling, and interpretation that affect discrete movement models. They
      can, however, be challenging to estimate, have been presented in inconsistent
      ways, and are not widely used. METHODS: We review the literature on integrated
      Ornstein-Uhlenbeck velocity models and propose four fundamental correlated
      velocity movement models (CVM's): random, advective, rotational, and rotational
      advective. The models are defined in terms of biologically meaningful speeds and
      time scales of autocorrelation. We summarize several approaches to estimating the
      models, and apply these tools for the higher order task of behavioral
      partitioning via change point analysis. RESULTS: An array of simulation
      illustrate the precision and accuracy of the estimation tools. An analysis of a
      swimming track of a bowhead whale (Balaena mysticetus) illustrates their
      robustness to irregular and sparse sampling and identifies switches between
      slower and faster, and directed vs. random movements. An analysis of a short
      flight of a lesser kestrel (Falco naumanni) identifies exact moments when
      switches occur between loopy, thermal soaring and directed flapping or gliding
      flights. CONCLUSIONS: We provide tools to estimate parameters and perform change
      point analyses in continuous time movement models as an R package (smoove). These
      resources, together with the synthesis, should facilitate the wider application
      and development of correlated velocity models among movement ecologists.

PMID- 28496984
TI  - Functional conductive nanomaterials via polymerisation in nano-channels: PEDOT in
      a MOF.
AB  - Reactions inside the pores of metal-organic frameworks (MOFs) offer potential for
      controlling polymer structures with regularity to sub-nanometre scales. We report
      a wet-chemistry route to poly-3,4-ethylenedioxythiophene (PEDOT)-MOF composites.
      After a two-step removal of the MOF template we obtain unique and stable
      macroscale structures of this conductive polymer with some nanoscale regularity.

PMID- 28496985
TI  - The effects of dietary macronutrient composition on lipid metabolism-associated
      factor gene expression in the adipose tissue of chickens are influenced by
      fasting and refeeding.
AB  - BACKGROUND: Broiler chickens are compulsive feeders that become obese as
      juveniles and are thus a unique model for metabolic disorders in humans. However,
      little is known about the relationship between dietary composition, fasting and
      refeeding and adipose tissue physiology in chicks. Our objective was to determine
      how dietary macronutrient composition and fasting and refeeding affect chick
      adipose physiology during the early post-hatch period. METHODS: Chicks were fed
      one of three isocaloric diets after hatch: high-carbohydrate (HC; control), high
      fat (HF; 30% of ME from soybean oil) or high-protein (HP; 25% vs. 22% crude
      protein). At 4 days post-hatch, chicks were fed (continuous ad libitum access to
      food), fasted (3 h food withdrawal), or refed (fasted for 3 h and refed for 1 h).
      Subcutaneous, clavicular, and abdominal adipose tissue was collected for
      histological analysis and to measure gene expression, and plasma to measure non
      esterified fatty acid (NEFA) concentrations (n = 6-10 per group). RESULTS:
      Adipose tissue weights were reduced in chicks that were fed the HP diet and
      adipocyte diameter was greater in the adipose tissue of chicks that ate the HF
      diet. Consumption of diets differing in protein and fat content also affected
      gene expression; mRNAs encoding fatty acid binding protein 4 and a lipolytic
      enzyme, monoglyceride lipase, were greater in chicks fed the HC and HF than HP
      diet in all three adipose tissue depots. Fasting influenced gene expression in a
      depot-dependent manner, where most fasting and refeeding-induced changes were
      observed in the clavicular fat of chicks that consumed the HC diet. Fasting
      increased plasma NEFA concentrations in chicks fed the HC and HP diets.
      CONCLUSIONS: The decreased adipose tissue deposition in chicks fed the HP diet is
      likely explained by decreased rates of adipogenesis. Consumption of the HF diet
      was associated with greater adipose tissue deposition and larger adipocytes,
      likely as a result of greater rates of adipocyte hypertrophy. The depot-dependent
      effects of diet and fasting on gene expression may help explain mechanisms
      underlying metabolic distinctions among subcutaneous and visceral fat depots in
      humans.

PMID- 28496986
TI  - A case of stiff dog syndrome associated with anti-glutamic acid decarboxylase
      antibodies.
AB  - BACKGROUND: The stiff person syndrome (SPS) is a rare and debilitating autoimmune
      disorder with an unknown pathogenesis and variable clinical presentation that can
      present a diagnostic challenge. Although entities that clinically mimic stiff
      person spectrum disorders (SPSD) have manifested in horses, they have not been
      reported in dogs. CASE PRESENTATION: We describe a 2-year-old beagle dog
      presented for progressive attacks of muscular rigidity and lordosis with
      superimposed spasms of the appendicular muscles triggered by tactile stimulation
      which resulted in marked gait impairment. Resting electromyography revealed
      continuous motor unit activity in the axial musculature. Compared to age-matched
      healthy beagle dogs, this patient had elevated glutamic acid decarboxylase
      antibody concentrations in serum and cerebrospinal fluid. CONCLUSION: This dog
      presented with phenotypic, electrodiagnostic, and immunologic criterion
      consistent with an SPSD, including elevated anti-GAD antibody titers, which we
      have termed the "stiff dog syndrome (SDS)". Durable clinical improvement was
      achieved with symptomatic and immunosuppressive treatments including baclofen,
      gabapentin, prednisone, and intravenous immunoglobulin.

PMID- 28496987
TI  - Effect of health foods on cytochrome P450-mediated drug metabolism.
AB  - BACKGROUND: Health foods have been widely sold and consumed in Japan. There has
      been an increase in reports of adverse effects in association with the expanding
      health food market. While health food-drug interactions are a particular concern
      from the viewpoint of safe and effective use of health foods, information
      regarding such interactions is limited owing to the lack of established methods
      to assess the effects of health food products on drug metabolism. We therefore
      developed cells that mimicked the activities of cytochrome P450 1A2 (CYP1A2),
      CYP2C9, CYP2C19, CYP2D6, and CYP3A4, which strongly contribute to drug metabolism
      in human hepatocytes, and established a system to assess the inhibitory activity
      of health foods toward P450-mediated metabolism. METHODS: We simultaneously
      infected HepG2 cells with five P450-expressing adenoviruses (Ad-CYP1A2, Ad
      CYP2C9, Ad-CYP2C19, Ad-CYP2D6, and Ad-CYP3A4) to mimic the activity levels of
      these P450s in human hepatocytes, and named them Ad-P450 cells. The activity
      levels of P450s in Ad-P450 cells and human hepatocytes were calculated via
      simultaneous liquid chromatography/tandem mass spectrometry analysis utilizing a
      P450 substrate cocktail. RESULTS: We established Ad-P450 cells mimicking the
      activity levels of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in human
      hepatocytes. We determined the Km values of P450 substrates and IC50 values of
      P450 inhibitors in Ad-P450 cells. These values were approximately equivalent to
      those obtained in previous studies. We investigated the inhibitory effects of 172
      health foods that were recently in circulation in Japan on P450-mediated
      metabolism using Ad-P450 cells. Of the 172 health foods, five products (two
      products having dietary effects, one turmeric-based product, one collagen-based
      product, and one propolis-containing product) simultaneously inhibited the five
      P450s by more than 50%. Another 29 products were also confirmed to inhibit one or
      more P450s. CONCLUSIONS: We established a comprehensive assessment system to
      elucidate the effects of health foods on P450-mediated metabolism and identified
      the inhibitory activity of 34 of 172 health foods toward the drug-metabolizing
      P450s. Our results may provide useful information to predict health food-drug
      interactions.

PMID- 28496989
TI  - Correction.
AB  - [This corrects the article on p. 349 in vol. 40.].

PMID- 28496988
TI  - Randomised controlled field study to evaluate the efficacy and clinical safety of
      a single 8 mg/kg injectable dose of marbofloxacin compared with one or two doses
      of 7.5 mg/kg injectable enrofloxacin for the treatment of Actinobacillus
      pleuropneumoniae infections in growing-fattening pigs in Europe.
AB  - BACKGROUND: Acute outbreaks of Actinobacillus pleuropneumoniae (APP) require
      rapid, effective, parenteral antimicrobial treatment. The efficacy and safety of
      a single, short-acting, high dose of marbofloxacin (Forcyl(r) swine 160 mg/mL)
      compared with 1 or 2 doses of 7.5 mg/kg enrofloxacin in APP outbreaks in European
      farms was studied. METHODS: A controlled, randomised block, blinded, multicentre,
      field study was conducted on four farms with acute respiratory disease associated
      with APP. Animals with clinical signs of respiratory disease were allocated
      similarly to intramuscular treatments of either a single dose 8 mg/kg
      marbofloxacin on day 0 or, 7.5 mg/kg enrofloxacin (Baytril 1nject(r)) on day 0
      and again on day 2, if clinical signs had not improved. RESULTS: The results were
      similar for intention to treat (242 pigs) and per protocol populations (239
      pigs). On day 0, all pigs had pyrexia (means, 40.6  degrees C), moderate to
      severe clinical signs (depression, cough, dyspnoea). Following treatment, animals
      improved rapidly and on day 7, clinical signs were absent or mild in all pigs and
      mean temperatures for each treatment were <39.5  degrees C (P > 0.05). The
      primary efficacy criterion, animals cured, for marbofloxacin and enrofloxacin was
      81.8 and 81.4% on day 7, and 84.2 and 82.2% on day 21, respectively. Results for
      cure, respiratory disease removals and mortalities, and relapses were compared
      using confidence intervals and confirmed that marbofloxacin was non-inferior to
      enrofloxacin (P > 0.05). There were no significant treatment differences in live
      weight gains, adverse events and injection site reactions (<2.5% animals) (P >
      0.05). Significantly more animals developed concurrent disorders in the
      enrofloxacin (7.5%) than marbofloxacin (0.0%) group (P < 0.01). On day 0, the
      MIC90 values of APP for marbofloxacin and enrofloxacin were 0.06 MUg/mL for APP,
      less than the clinical breakpoints. CONCLUSIONS: Marbofloxacin (single dose of 8
      mg/kg) and enrofloxacin (1 or 2 doses of 7.5 mg/kg) were clinically safe and
      effective in the treatment of clinical respiratory disease associated
      predominantly with APP in four European commercial, fattening pig herds.

PMID- 28496991
TI  - TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin
      CDK-Cks1.
AB  - Eukaryotic cell cycle progression through G1-S is driven by hormonal and growth
      related signals that are transmitted by the target of rapamycin complex 1 (TORC1)
      pathway. In yeast, inactivation of TORC1 restricts G1-S transition due to the
      rapid clearance of G1 cyclins (Cln) and the stabilization of the B-type cyclin
      (Clb) cyclin-dependent kinase (CDK) inhibitor Sic1. The latter mechanism remains
      mysterious but requires the phosphorylation of Sic1-Thr173 by Mpk1 and
      inactivation of the Sic1-pThr173-targeting phosphatase (PP2ACdc55) through
      greatwall kinase-activated endosulfines. Here we show that the Sic1-pThr173
      residue serves as a specific docking site for the CDK phospho-acceptor subunit
      Cks1 that sequesters, together with a C-terminal Clb5-binding motif in Sic1, Clb5
      CDK-Cks1 complexes, thereby preventing them from flagging Sic1 for ubiquitin
      dependent proteolysis. Interestingly, this functional switch of Sic1 from a
      target to an inhibitor of cyclin-CDK-Cks1 also operates in proliferating cells
      and is coordinated by the greatwall kinase, which responds to both Cln-CDK
      dependent cell-cycle and TORC1-mediated nutritional cues.

PMID- 28496990
TI  - mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability
      to regulatory T cells by controlling kinesin KIF13A.
AB  - Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P
      bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important
      role in T-cell activation, migration and contraction. However, molecular
      mechanisms controlling M6PR expression in T cells remain poorly understood. Here,
      we show that M6PR expression on T cells is distinctively controlled by two common
      gamma-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR
      expression is not caused by an altered synthesis of M6PR protein, but is a result
      of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto
      cell surfaces. Using signaling pathway-specific inhibitors, we determine that IL
      2 and IL-7 distinctly regulate KIF13A and beta1-adaptin and cell-surface M6PR by
      controlling a kinase mammalian target of rapamycin complex-1 (mTORC1).
      Inflammatory cytokine IL-2 and prosurvival cytokine IL-7 induce strong and weak
      activation of mTORC1, leading to up- and downregulation of motor-protein KIF13A
      and KIF13A-motorized M6PR on T cells, and formation of IL-2 and IL-7 effectors
      with M6PRhigh and M6PRlow cell-surface expression, respectively. Inhibition of
      mTORC1 by rapamycin reduces T-cell expression of KIF13A and cell-surface M6PR,
      and increases T-cell survival in Listeria monocytogenes-infected mice. Using
      regulatory T (Treg)-cell-enriched mouse tumor model, we determine that M6PRhigh
      IL-2 effectors but not M6PRlow IL-7 effectors adoptively transferred into tumors
      are vulnerable to Treg Gzm-B-mediated cell apoptosis. Inhibition of mTORC1 or
      small interfering RNA-mediated knockdown of KIF13A or M6PR renders IL-2 effectors
      refractory to Treg Gzm-B lethal hit. Overall, our data offer novel mechanistic
      insights into T-cell M6PR regulation, and Treg-resistant/Treg-susceptible
      phenomenon. Furthermore, regulation of T-cell fate vis-a-vis Treg suppression via
      the mTORC1-KIF13A-M6PR axis provides a proof of concept for therapeutic
      strategies to target cancer, infectious and autoimmune diseases.

PMID- 28496992
TI  - Flavored little cigar smoke induces cytotoxicity and apoptosis in airway
      epithelia.
AB  - Addition of flavors reduces the harsh taste of tobacco, facilitating the
      initiation and maintenance of addiction among youths. Flavored cigarettes (except
      menthol) are now banned. However, the legislation on little cigars remains
      unclear and flavored little cigars are currently available for purchase. Since
      inhaled tobacco smoke directly exerts toxic effects on the lungs, we tested
      whether non-flavored and flavored little cigar smoke exposure had the potential
      for harm in cultured pulmonary epithelia. We cultured Calu-3 lung epithelia on
      both 96-well plates and at the air-liquid interface and exposed them to smoke
      from non-flavored Swisher Sweets and flavored (sweet cherry, grape, menthol,
      peach and strawberry) Swisher Sweets little cigars. Irrespective of flavor, acute
      little cigar smoke exposure (10*35 ml puffs) significantly increased cell death
      and decreased the percentage of live cells. Chronic exposure (10*35 ml puffs per
      day for 4 days) of smoke to Calu-3 cultures significantly increased lactate
      dehydrogenase release, further indicating toxicity. To determine whether this
      exposure was associated with increased cell death/apoptosis, a protein array was
      used. Chronic exposure to smoke from all types of little cigars induced the
      activation of the two major apoptosis pathways, namely the intrinsic
      (mitochondrial-mediated) and the extrinsic (death receptor-mediated) pathways.
      Both flavored and non-flavored little cigar smoke caused similar levels of
      toxicity and activation of apoptosis, suggesting that flavored and non-flavored
      little cigars are equally harmful. Hence, the manufacture, advertisement, sale
      and use of both non-flavored and flavored little cigars should be strictly
      controlled.

PMID- 28496993
TI  - Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic.
AB  - A pilot program was initiated using whole genome sequencing (WGS) to diagnose
      suspected genetic disorders in the Genetics Clinic at Children's Hospital of
      Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we
      obtained a 14% (3/22) diagnosis rate over 2 years; with subsequent reanalysis,
      this increased to 36% (8/22). Disease causing variants were identified in SKIV2L,
      CECR1, DGKE, PYCR2, RYR1, PDGFRB, EFTUD2, and BCS1L. In 75% (6/8) of diagnosed
      cases, the diagnosis affected treatment and/or medical surveillance.
      Additionally, one case demonstrated a homozygous A18V variant in VLDLR that
      appears to be associated with a previously undescribed phenotype.

PMID- 28496994
TI  - Novel Causative Variants in DYRK1A, KARS, and KAT6A Associated with Intellectual
      Disability and Additional Phenotypic Features.
AB  - Patients with unclear patterns of developmental and cognitive delay may go years
      without a definitive diagnosis despite extensive testing due to overlapping
      phenotypes of many genetic disorders. In this study, we identified causative
      variants in DYRK1A, KARS, or KAT6A in four individuals with global developmental
      delay and various findings including microcephaly and sensorineural hearing loss
      using whole exome sequencing. We present the cognitive, neurologic, and physical
      findings of four individuals to expand the clinical knowledge of possible
      features of the phenotypes of three rare genetic disorders. Through this process,
      we provide support for the use of whole exome sequencing in the setting of
      severe, intellectual disability or in those in whom a genetic disorder is
      suspected despite initial negative testing.

PMID- 28496995
TI  - Genomic Microarray in Intellectual Disability: The Usefulness of Existing Systems
      in the Interpretation of Copy Number Variation.
AB  - Whole genome array technology is an essential tool for the detection of a large
      number of copy number variants (CNVs) in patients with ID and/or multiple
      congenital anomalies. However, the clinical significance of some microimbalances
      is not known. In this article, we succeeded to detect seven new variations of
      unknown significance (dup12p13.33, dup2p16.3, dupXq13.2, del12q24.33,
      dup16p13.11, trip4q22.1, and dup9p21.3), one CNV classified as known pathogenic
      syndrome (del22q13.31-q33), and one CNV classified as potentially pathogenic
      (del11q24.3). We emphasize the role of comparative genomic hybridization arrays
      in the investigation of intellectual disability and evaluate the usefulness of
      existing systems in the interpretation of CNVs.

PMID- 28496996
TI  - Anterior Abdominal Wall Defects, Diaphragmatic Hernia, and Other Major Congenital
      Malformations of the Musculoskeletal System in Barbados, 1993-2012.
AB  - This study describes the prevalence and patterns of major congenital
      malformations of the musculoskeletal system and the resulting morbidity and
      mortality. It is a retrospective population-based study over the period 1993 to
      2012. The overall prevalence of major congenital malformations of the
      musculoskeletal system was 9.02/10,000 live births. The prevalences of
      omphalocele, gastroschisis, and diaphragmatic hernia were 2.53, 2.22, and 1.42
      per 10,000 live births, respectively. The case fatality ratio for the
      omphalocele, gastroschisis, and diaphragmatic hernia was 12.5, 28.5, and 67%,
      respectively. In conclusion, the prevalence rate of the major congenital
      malformations of the musculoskeletal system was higher than those reported in
      retrospective studies from other countries and remained static during the study
      period. These defects were associated with a high mortality rate and contributed
      significantly to the overall neonatal mortality in this country.

PMID- 28496997
TI  - A New Split Hand/Foot Malformation with Long Bone Deficiency Familial Case.
AB  - Split hand/foot malformation with long bone deficiency (SHFLD) is a congenital
      limb anomaly where hands and/or feet cleft and syndactyly are associated with
      long bone defects, usually involving the tibia. Previously published data
      reported that 17p13.3 chromosomal duplication, including the BHLHA9 gene, has
      been associated with the distinct entity, termed SHFLD3 (OMIM 612576), inherited
      as an autosomal dominant trait. Here, we present a family with three members
      affected by SHFLD harboring BHLHA9 duplication. We exploited in vitro
      differentiation system to promote proband's skin fibroblasts toward osteoblastic
      lineage, and we observed a slight but consistent delay in the mineralization
      pattern. This result possibly suggests an impairment of the osteogenic process in
      the affected members.

PMID- 28496998
TI  - Multisystem Involvement in a Patient with a PTCH1 Mutation: Clinical and Imaging
      Findings.
AB  - In this article, we report on a Brazilian female patient born to consanguineous
      parents and presenting with alobar holoprosencephaly, severe eye involvement, and
      unusual skin hyperpigmented lesions. She was found to have a mutation (c.2240T >
      C; p.Val751Gly) in exon 15 of the PTCH1 gene. Mutations in this gene are
      associated with the nevoid basal cell carcinoma syndrome (NBCCS, OMIM 109400)
      and, in other instances, with holoprosencephaly (holoprosencephaly-7, OMIM
      610828). Severe eye involvement ranging from orbital coloboma to microphthalmia
      has been seldom reported in patients with NBCCS with PTCH1 mutations. To our
      knowledge, this is the first report of an individual with central nervous system,
      skin, and eye manifestations due to a PTCH1 mutation. Mechanisms involved in
      these multisystem manifestations are discussed.

PMID- 28496999
TI  - The Clinical Manifestations and Genetic Implications of Baraitser-Winter Syndrome
      Type 2.
AB  - An 18-year-old Caucasian male was born by cesarean section weighing 2.6 kg (5 lb
      14 oz) at birth after an uncomplicated pregnancy with no perinatal complications.
      Around 4 to 5 months of age, the patient's mother initially became concerned as
      he was experiencing signs of developmental delay and a mild floppy tone, in
      addition to facial features that resembled some form of mental retardation. The
      patient's older brother also experienced similar developmental symptoms and
      facial features that presented around the same age period as our patient. It was
      initially thought to be Down syndrome; however, both the patient and his brother
      tested negative for Down syndrome on chromosomal analyses. There was also a
      question of whether the patient had some form of autism spectrum disorder, but
      doctors were unable to specifically confirm this. Now at the age of 18 years, the
      patient has no understandable speech with distinctive facial features such as a
      broad nasal bridge and prominent epicanthic folds, lissencephaly, smaller than
      average head size, intellectual disability, and hearing loss. It was discovered,
      through trio-based exome sequencing, that the patient had a de novo missense
      mutation (p.Ser155Phe) in the ACTG1 gene, which has been linked to the rare
      syndrome known as Baraister-Winter syndrome type 2. Baraitser-Winter syndrome 2
      is a unique variant that is clinically similar to Baraitser-Winter syndrome type
      1; however, only seven previous cases have been reported.

PMID- 28497000
TI  - What Is the Teratogenic Risk of Mycophenolate?
AB  - Mycophenolate is often used in the management of systemic lupus erythematosus. It
      has often been associated with significant fetal embryopathy, including fetal
      loss and multiple anomalies. The Food and Drug Administration has directed that
      women should be counseled regarding this prior to initiating treatment with this
      drug. Isolated total anomalous pulmonary venous return (TAPVR) is a rare
      association seen with its use in pregnancy.

PMID- 28497001
TI  - Klinefelter Syndrome in Association with Tetralogy of Fallot and Congenital
      Diaphragmatic Hernia.
AB  - Klinefelter syndrome (KS) is the most common sex chromosomal aneuploidy in males.
      Major cardiovascular and diaphragmatic anomalies are uncommon in this syndrome.
      Here we report an infant with KS who had tetralogy of Fallot and congenital
      diaphragmatic hernia, all of which were identified prenatally and managed
      successfully after birth. Microarray analysis did not reveal any deletions or
      duplications other than the additional X-chromosome, to account for the
      additional abnormalities in this infant. To the authors' knowledge, this is the
      first such report of major cardiac and diaphragm anomaly occurring together, in
      an infant with KS.

PMID- 28497002
TI  - Overlap between Fibular Aplasia, Tibial Campomelia, and Oligosyndactyly and
      Fuhrmann's Syndromes in an Egyptian Female Infant.
AB  - We report a rare congenital limb defect with combined features of both fibular
      aplasia, tibial campomelia, and oligosyndactyly (FATCO) and Fuhrmann's syndromes.
      A female newborn infant, born to nonconsanguineous Egyptian parents, presented
      with isolated abnormalities of the lower limbs comprising bilateral shortening
      and anterior bowing of the lower limbs at the distal third of the tibia and split
      foot. Radiographic examination revealed complete absence of both fibulae,
      anterolateral bowing and shortening of the tibia, bowing of the femora, and
      absence of several metatarsal and phalangeal bones. The upper limbs were
      clinically and radiologically normal, and the infant had neither facial
      dysmorphism nor other associated visceral anomalies. The presented case
      highlights an extremely rare limb deficiency syndrome, and together with
      additional case reports, it could be useful to further delineate this condition.

PMID- 28497003
TI  - Achondroplasia and Biliary Atresia: A Rare Association and Review of Literature.
AB  - Achondroplasia (ACH) occurs in most cases as de novo mutations of the gene
      encoding fibroblast growth factor receptor 3 (FGFR3). Biliary atresia (BA) is a
      progressive neonatal inflammatory and fibro-obliterative cholangiopathy affecting
      the extra- and intrahepatic biliary tree to varying degrees, and it results in
      obstruction to bile flow and cholestatic jaundice in neonates. BA is thought to
      be a multifactorial disease, genome association studies have shown abnormalities
      in susceptibility genes, and levels of fibroblast growth factor 21 (FGF21) and
      fibroblast growth factor 23 (FGF23) have been noted to be increased. These two
      conditions occurring in the same patient has never been reported before.

PMID- 28497004
TI  - Progressive Familial Intrahepatic Cholestasis Type 2 in an Indian Child.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is a chronic cholestasis
      syndrome that begins in infancy and usually progresses to cirrhosis within the
      first decade of life. There are three varieties of PFIC described: PFIC-1 occurs
      due to mutations in the ATP8B1 gene mapped to 18q21.31, PFIC-2 due to mutations
      in ABCB11 mapped to 2q24, and PFIC-3 due to mutations in ABCB4 located on
      7q21.12. We report an Indian child whose mutation analysis was suggestive of PFIC
      2. He underwent a biliary diversion at 31/2 years of age but subsequently died
      secondary to massive hematemesis.

PMID- 28497006
TI  - Under Pressure: Intraluminal Filling Pressures of Postpartum Hemorrhage Tamponade
      Balloons.
AB  - Objective Uterine tamponade by fluid-filled balloons is now an accepted method of
      controlling postpartum hemorrhage. Available tamponade balloons vary in design
      and material, which affects the filling attributes and volume at which they
      rupture. We aimed to characterize the filling capacity and pressure-volume
      relationship of various tamponade balloons. Study Design Balloons were filled
      with water ex vivo. Intraluminal pressure was measured incrementally (every 10 mL
      for the Foley balloons and every 50 mL for all other balloons). Balloons were
      filled until they ruptured or until 5,000 mL was reached. Results The Foley
      balloons had higher intraluminal pressures than the larger-volume balloons. The
      intraluminal pressure of the Sengstaken-Blakemore tube (gastric balloon) was
      initially high, but it decreased until shortly before rupture occurred. The Bakri
      intraluminal pressure steadily increased until rupture occurred at 2,850 mL. The
      condom catheter, BT-Cath, and ebb all had low intraluminal pressures. Both the BT
      Cath and the ebb remained unruptured at 5,000 mL. Conclusion In the setting of
      acute hemorrhage, expeditious management is critical. Balloons that have a low
      intraluminal pressure-volume ratio may fill more rapidly, more easily, and to
      greater volumes. We found that the BT-Cath, the ebb, and the condom catheter all
      had low intraluminal pressures throughout filling.

PMID- 28497007
TI  - Accuracy of Blood Loss Measurement during Cesarean Delivery.
AB  - Objective This study aims to compare the accuracy of visual, quantitative
      gravimetric, and colorimetric methods used to determine blood loss during
      cesarean delivery procedures employing a hemoglobin extraction assay as the
      reference standard. Study Design In 50 patients having cesarean deliveries blood
      loss determined by assays of hemoglobin content on surgical sponges and in
      suction canisters was compared with obstetricians' visual estimates, a
      quantitative gravimetric method, and the blood loss determined by a novel
      colorimetric system. Agreement between the reference assay and other measures was
      evaluated by the Bland-Altman method. Results Compared with the blood loss
      measured by the reference assay (470 +/- 296 mL), the colorimetric system (572 +/
      334 mL) was more accurate than either visual estimation (928 +/- 261 mL) or
      gravimetric measurement (822 +/- 489 mL). The correlation between the assay
      method and the colorimetric system was more predictive (standardized coefficient
      = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized
      coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination
      (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During
      cesarean delivery, measuring blood loss using colorimetric image analysis is
      superior to visual estimation and a gravimetric method. Implementation of
      colorimetric analysis may enhance the ability of management protocols to improve
      clinical outcomes.

PMID- 28497005
TI  - The Transcription Regulator Kruppel-Like Factor 4 and Its Dual Roles of Oncogene
      in Glioblastoma and Tumor Suppressor in Neuroblastoma.
AB  - The Kruppel-like factor 4 (KLF4) gene is located on chromosome 9q31. All of the
      currently known 17 KLF transcription regulators that have similarity with members
      of the specificity protein family are distinctly characterized by the Cys2/His2
      zinc finger motifs at their carboxyl terminals for preferential binding to the
      GC/GT box or the CACCC element of the gene promoter and enhancer regions. KLF4 is
      a transcriptional regulator of cell proliferation, differentiation, apoptosis,
      migration, and invasion, emphasizing its importance in diagnosis and prognosis of
      particular tumors. KLF4 has been implicated in tumor progression as well as in
      tumor suppression, depending on tumor types and contexts. Different studies so
      far strongly suggest that KLF4 acts as an oncogene in glioblastoma, which is the
      most malignant and prevalent brain tumor in human adult. It is now well
      established that the presence of glioblastoma stem cells (GSCs) in glioblastoma
      causes therapy resistance and progressive growth of the tumor. Because KLF4 is
      one of the key stemness factors in GSCs, it is likely that KLF4 contributes
      significantly to the survival of GSCs and the recurrence of glioblastoma. On the
      other hand, recent studies show that KLF4 can act as a tumor suppressor in human
      malignant neuroblastoma, which is a deadly tumor mostly in children, by
      inhibiting the cell cycle and activating the cell differentiation and death
      pathways. Our increasing understanding of the molecular mechanisms of the
      contrasting roles of KLF4 in glioblastoma and neuroblastoma is useful for
      superior diagnosis, therapy, and prognosis of these tumors of the nervous system.

PMID- 28497008
TI  - THE POSITIVITY OFFSET THEORY OF ANHEDONIA IN SCHIZOPHRENIA.
AB  - Prior studies have concluded that schizophrenia patients are not anhedonic
      because they do not report reduced experience of positive emotion to pleasant
      stimuli. The current study challenged this view by applying quantitative methods
      validated in the Evaluative Space Model of emotional experience to test the
      hypothesis that schizophrenia patients evidence a reduction in the normative
      "positivity offset" (i.e., the tendency to experience higher levels of positive
      than negative emotional output when stimulus input is absent or weak).
      Participants included 76 schizophrenia patients and 60 healthy controls who
      completed an emotional experience task that required reporting the level of
      positive emotion, negative emotion, and arousal to photographs. Results indicated
      that although schizophrenia patients evidenced intact capacity to experience
      positive emotion at high levels of stimulus input, they displayed a diminished
      positivity offset. Reductions in the positivity offset may underlie volitional
      disturbance, limiting approach behaviors toward novel stimuli in neutral
      environments.

PMID- 28497009
TI  - False Positive Positron Emission Tomography / Computed Tomography Scans in
      Treated Head and Neck Cancers.
AB  - OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) imaging for
      head and neck cancers (HNC) is commonly utilized for post-treatment assessment.
      Though PET/CT in this setting has been reported to have high negative predictive
      values (> 90%), positive predictive values have been reported at approximately
      50%, leading to high rates of false positivity (FP) and troubling management
      decisions for both patient and practitioner. The objective of this study was to
      identify patient, disease, treatment and imaging factors that might be associated
      with a higher likelihood of FP on initial post-treatment PET/CT imaging for
      patients treated for HNC. MATERIALS AND METHODS: A retrospective chart review was
      performed on 84 patients treated for HNC who received radiation therapy (RT) as
      part of their overall management from October 2005 to August 2013. Of the
      patients screened, 19 were found to have mucosally based squamous cell carcinoma
      (SCC) with positive initial post-treatment PET/CT studies (23%). Fisher's exact
      test was used to analyze the association between categorical variables and FP,
      including patient's gender, disease laterality, primary tumor site and stage,
      nodal and overall stage, high dose RT fraction size, number of RT fractions
      completed, total RT dose, biologically effective dose and timing of PET/CT
      acquisition. Wilcoxon rank-sum test was used to analyze the association between
      continuous variables and FP, including patient age, total elapsed days of RT, an
      amount of infused fluorodeoxyglucose 18F-FDG, pre-PET/CT serum glucose levels,
      and maximum standardized uptake value SUVmax. Statistically significant findings
      were those that were deemed p <0.05. RESULTS: Among patients with positive
      initial post-treatment PET/CT scans for treated HNC, there was a lower proportion
      of higher primary disease stage associated with FP versus true positivity (T
      stage 3-4: 20 vs 78%, respectively, p=0.023). We also discovered that 50% of
      patients that underwent confirmation for FP findings suffered serious
      complications as a direct consequence of invasive exploratory procedures.
      CONCLUSIONS: Although PET/CT is known for its exceptional negative predictive
      value (> 90%) in the post-treatment setting for HNC, high rates of FP remains a
      clinical challenge. Our study suggests that tumor stage (T-stage) may impact FP
      rates in positive initial post-treatment PET/CT scans. We recommend careful
      multidisciplinary discussion regarding positive PET/CT studies in the post
      treatment setting for HNC, particularly if invasive intervention is considered.

PMID- 28497010
TI  - A Review of the Value of Procalcitonin as a Marker of Infection.
AB  - Septicemia is a growing problem within the United States (US), which increases
      mortality and the cost of care. Procalcitonin is a pro-inflammatory marker that
      could be useful in the diagnosis of infection. In the past, procalcitonin levels
      have been evaluated to diagnose sepsis or guide antibiotic therapy, but it was
      not determined if it would differentiate between sepsis and other causes of
      inflammation. Studies reviewed here showed procalcitonin to be a useful biomarker
      as an indication of bacterial infection. Infections can be diagnosed earlier and
      managed appropriately to avoid progression to septicemia, reduce mortality, and
      overall medical costs.

PMID- 28497011
TI  - Reference Data for Standardized Quality of Life Questionnaires in Indian Patients
      with Brain Metastases from Non-small Cell Lung Cancer: Results from a Prospective
      Study.
AB  - INTRODUCTION: Reference data for European Organization for Research and Treatment
      of Cancer (EORTC) quality of life questionnaires do not include studies from the
      Indian subcontinent. The objective of the current study was to establish a
      reference dataset for Indian patients of non-small cell lung cancer (NSCLC)
      presenting with brain metastases (BM). MATERIAL AND METHODS: One hundred forty
      patients with NSCLC with BM treated between 2012-2015 were registered in a
      prospective cohort study (CTRI/2013/01/003299). The baseline quality of life was
      evaluated using the EORTC general quality of life questionnaire QLQ-C30 and lung
      cancer specific module LC13. Minimum important difference (MID) scores for
      individual domains of the EORTC QLQ-C30 and LC13 questionnaires were derived (MID
      = 0.2 x standard deviation) from the reference data for patients with
      recurrent/metastatic lung cancers. In addition, a systematic review was conducted
      to identify studies reporting baseline quality of life scores for
      recurrent/metastatic NSCLC. RESULTS: Scores of several functional as well as
      symptom scales in the current NSCLC population differed by more than the MID from
      the baseline mean scores in the reference EORTC population as well as that
      reported from other studies. Differences in mean score from the EORTC reference
      data ranged from 6.2 and 9.4 points for the role functioning and cognitive
      functioning domains. In the symptom scales, the largest differences were observed
      for the financial difficulties (23.9) scores for the QLQ-C30 and peripheral
      neuropathy (21.7) for LC13 questionnaires. CONCLUSION: The current study
      demonstrates that baseline reference scores need to be established for patients
      from the Indian subcontinent. The findings from the current study have important
      implications for studies employing quality of life (QOL) assessment in the Indian
      NSCLC patient population.

PMID- 28497012
TI  - Electrocatalytic Oxidation of Alcohols, Tripropylamine, and DNA with Ligand-Free
      Gold Nanoclusters on Nitrided Carbon.
AB  - Electrocatalytic properties of ligand-free gold nanoclusters (AuNCs, <2 nm) grown
      on nitrided carbon supports (denoted as AuNCs@N-C) were evaluated for the
      oxidation of representative organic molecules including alcohols, an amine, and
      deoxyguanosine in oligonucleotides. AuNCs@N-C catalysts were incorporated into
      films of architecture {PDDA/AuNCs@N-C} n by using layer-by-layer assembly with
      oppositely charged poly(diallyldimethylammonium) (PDDA) on pyrolytic graphite
      (PG) electrodes. Cyclic voltammetry and electrochemical impedance spectroscopy
      (EIS) were used to survey the electrocatalytic properties of these AuNCs@N-C
      films. Ligand-free AuNCs in these films demonstrated excellent electrocatalytic
      oxidation activity with maximum peak currents and the lowest potentials for
      oxidizing ethanol, propanol, and tripropylamine (TprA) compared to controls with
      Au-surface capping agents or to larger sized Au nanocrystals on the nitrided
      carbon supports. EIS kinetic studies showed that ligand-free AuNCs films have the
      smallest charge-transfer resistance, largest electrochemically active surface
      area, and largest apparent standard rate constants, as compared to the control
      films for all compounds examined. DNA films on AuNCs@N-C were oxidized at
      deoxyguanosine moieties with good catalytic activity that depended on charge
      transport within the films.

PMID- 28497015
TI  - Aesthetic breast surgery, scientific approach.

PMID- 28497014
TI  - The E. histolytica Genome Structure and Virulence.
AB  - The outcome of an Entamoeba histolytica infection is variable and the
      contribution of genetic diversity within E. histolytica to human disease is not
      fully understood. The information provided by the whole genome sequence of the E.
      histolytica reference laboratory strain (HM-1:IMSS) and thirteen additional
      laboratory strains have been made publically available. In this review theories
      on the source of the unexpected level of structural diversity found in E.
      histolytica will be discussed.

PMID- 28497013
TI  - Racial/ethnic disparities in environmental endocrine disrupting chemicals and
      women's reproductive health outcomes: epidemiological examples across the life
      course.
AB  - Disparities in women's reproductive health outcomes across the life course have
      been well-documented. Endocrine disrupting chemicals may be one factor driving
      disparities, as studies suggest exposure to certain environmental endocrine
      disrupting chemicals, such as certain phthalates, bisphenol A, parabens and
      polybrominated diphenyl ethers are higher in non-whites. Yet, a limited amount of
      research has focused on these chemical exposures as a potential mediator of
      racial/ethnic differences in women's reproductive health outcomes, such as
      pubertal development, fibroids, infertility, and pregnancy complications. Given
      that race/ethnicity is a social construct, the purpose of this review was to
      present the current state of the literature on racial/ethnic disparities in both
      environmental endocrine disrupting chemicals, as well as associations between
      these chemicals and selected women's reproductive health outcomes. Our goal was
      to evaluate literature from populations based in the United States to: 1)
      characterize racial/ethnic differences in environmental endocrine disrupting
      chemicals and 2) systematically review literature on environmental endocrine
      disrupting chemicals and selected women's health outcomes in populations
      containing more than one racial/ethnic group. This review highlights the need for
      future work in determining whether higher exposures to some environmental
      endocrine disrupting chemicals might partly explain differences in women's
      reproductive health outcomes in these higher-exposure and high-risk groups.

PMID- 28497016
TI  - Small refinements in breast reconstruction: a technique for inframammary fold
      creation.
AB  - BACKGROUND: In breast reconstructive surgery, the inframammary fold (IMF) is an
      essential component of breast identity. The lack of the IMF following previous
      mastectomy requires restoration. We have developed a new IMF reconstruction
      technique using the posterior sheet (PS) of the expander capsule. This article
      presents our 10-year experience of performing this original technique during two
      stage breast reconstruction. METHODS: Preoperatively, the midline, lateral, and
      medial borders (MBs) of the implant pocket and the new IMF line were marked.
      After extracting the expander, the anterior sheet of the expander capsule was
      removed with the exception of its lowest 2-cm portion. Two needles were placed at
      the intersection of the new IMF line with the lateral border (LB) of the implant
      pocket and its MB. Within the pocket, horizontal dissection of the PS of the
      capsule was performed from one needle to another, after which the sheet was
      mobilized downward. The mobilized free border of the PS was pulled upward until
      the inframammary crease was at the new marked location, and then fixed with non
      absorbable interrupted sutures to the underlying tissues. An implant was placed
      over this layer. The covering tissues were then closed. RESULTS: A total of 321
      patients were included. The median age was 38 years (range, 18-58 years). No
      serious wound complications were observed. Breast-thoracic angle decreased in 21
      patients (6.5%), and the distance from the IMF to the lower border of breast
      segment III was greater than that of the contralateral breast in 14 patients
      (4.4%). CONCLUSION: This technique provides a well-defined IMF without
      indentations or retraction. The results are stable on long-term follow-up and
      provide a sharp breast-thoracic angle, which is crucial in creating natural
      looking ptosis of the reconstructed breast.

PMID- 28497017
TI  - Improving aesthetic outcomes in mastopexy with the "autoprosthesis" technique.
AB  - BACKGROUND: Many techniques have been described for mastopexy, with several types
      of skin incisions and parenchymal rearrangements. We present a parenchymal
      rearrangement technique allowing better upper pole fullness and nipple-areola
      complex (NAC) projection when performing a mastopexy, with a combination of a
      superior pedicle for the NAC and an inferiorly-based parenchymal flap, the so
      called "autoprosthesis". METHODS: From January 2008 to June 2015, 184 patients
      underwent "autoprosthesis" mastopexy. Patients' mean ages was 42 years. The mean
      follow-up period was 39 months. RESULTS: We reported no major complications. All
      the patients were satisfied with their post-operative unclothed and clothed
      appearance and overall body image as reported by our questionnaire. CONCLUSIONS:
      The autoprosthesis technique for mastopexy is a simple and safe, technique,
      allowing long-lasting results for breast projection and upper pole fullness.

PMID- 28497019
TI  - Anatomical basis of pedicles in breast reduction.
AB  - The mammary gland is composed of multiple tubules acinar pockets in which the
      secretory layer, connective tissue stroma, and fatty tissue all respond to
      hormonal and systemic influences. These structures are irrigated by three
      vascular pedicle branches, from the axillary artery, internal mammary artery, and
      intercostal artery. This vascular anastomotic arrangement forms the anatomical
      basis of the flaps used in breast reduction techniques. The veins form a strong
      subdermal network, latticed with the arterial network. The lymph vessels have
      three well-defined pedicles, skin, glandular and milk ducts that drain into
      internal, external, and posterior ducts. The understanding of these anatomical
      structures determines the selection of different pedicles in breast volume
      reduction and preservation of the nipple-areola complex circulation.

PMID- 28497018
TI  - Breast implant design.
AB  - Breast Augmentation remains as one of the most common procedures performed in the
      United States. This article explores the evolution of breast implants with
      special emphasis on the advancement of the silicone implants.

PMID- 28497020
TI  - Silicone breast implant rupture: a review.
AB  - Silicone breast implants have been in use for nearly 6 decades. In this time they
      have undergone significant changes in design and use. They have been subject to
      intense scrutiny with regard to safety and efficacy, including an almost 10 years
      moratorium on their use. The current generations of implants have been followed
      via the manufacturer's Core studies in order to obtain long term data regarding
      safety and complications. The results of the more recent studies are compiled in
      this review. Rupture rates are initially very low and begin to increase after 6-8
      years of implantation. Implant rupture may be detected by physical exam,
      ultrasound or magnetic resonance imaging (MRI). The majority of silicone implant
      ruptures are clinically undetectable. Symptomatic patients may present with
      capsular contracture, breast lumps or changes in breast shape. The most common
      cause of implant rupture is instrument damage during placement. Implant rupture
      may be confined to the peri-prosthetic capsule or may extravasate into the breast
      tissue. Patients with ruptured implants have been studied closely and the
      consensus of the literature states there are no health risks associated with
      implant rupture. Symptomatic patients with ruptured implants should be offered
      the choice of observation, or explantation and capsulectomy with or without
      replacement.

PMID- 28497021
TI  - Understanding rare adverse sequelae of breast implants: anaplastic large-cell
      lymphoma, late seromas, and double capsules.
AB  - Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a distinct
      type of T-cell lymphoma arising around breast implants. The United States FDA
      recently updated the 2011 safety communication, warning that women with breast
      implants may have a very low risk of developing ALCL adjacent to a breast
      implant. According to the World Health Organization, BI-LCL is not a breast
      cancer or cancer of the breast tissue; it is a lymphoma, a cancer of immune
      cells. BI-ALCL is highly curable in the majority of patients. Informed consent
      should include the risk of BI-ALCL with breast implant patients. Women with
      breast implants are encouraged to contact their plastic surgeon if they notice
      swelling, fluid collections, or unexpected changes in breast shape. Physicians
      are encouraged to send suspicious peri-prosthetic fluid for CD30
      immunohistochemistry, cell block cytology, and culture in symptomatic patients.
      An observation from reported cases indicates a predominance of textured device
      involvement. More information is needed to fully understand risk factors and
      etiology. The association of bacteria and biofilm with ALCL is currently being
      investigated and one theory is that biofilm may play a role in this disease
      process stressing the importance of best practice techniques intraoperatively.
      Recent studies have reported clinical presentation, prognosis, and treatment
      outcomes with long term followup demonstrating the critical role for surgical
      management.

PMID- 28497022
TI  - Patients' satisfaction with anatomic polyurethane implants.
AB  - This paper presents patients satisfaction using anatomical polyurethane breast
      implants. We performed surgery on 525 patients, 370 of which were primary and 155
      were secondary to various causes such as capsular contracture, ruptured implants,
      volume changes, and incorrect positioning of the implant. The advantages of
      silicone polyurethane covers shown high level of patient satisfaction, low
      incidence of capsular contracture, and absence of implant rotation, and late
      seroma.

PMID- 28497023
TI  - The waterfall effect in breast augmentation.
AB  - The 'waterfall effect' is a descriptive term to indicate a sliding ptosis of
      parenchymal breast tissue over a fixed or encapsulated implant. It occurs more
      frequently than surgeons anticipate and especially over the longer term after
      augmentation. Certain breast implants are more prone to contribute to this
      problem as are implants placed in submuscular pockets that ride high, especially
      in women with anatomical musculoskeletal variance or asymmetry. This article
      describes the aetiology of sliding ptosis in more detail, the relevant anatomy
      and the surgical correction. Understanding the problem enables the surgeon to
      plan the appropriate procedure and obtain proper informed consent. It is possible
      that a two stage procedure is necessary should the upper pole of breast require a
      debulk, either early (3 to 12 months) or later as the breast may slide with
      ageing of the tissues. The waterfall effect of breast parenchyma over implants is
      only apparent when the upper torso of the woman is undressed and she is in an
      erect posture. A significant number of women are happy with this situation and
      therefore no further action is required. Those that want an improved appearance
      in these circumstances can try autologous fat transfer to rebulk the surrounding
      tissues but generally the most likely solution involves a mastopexy with or
      without implant exchange. The results are highly rewarding but the scars are the
      legacy. Mastopexy augmentation is a difficult procedure and should only be
      performed by experienced surgeons. Many surgeons prefer a two stage approach with
      either an implant based augmentation first to limit scars and see if the patient
      is happy with the outcome or a first stage mastopexy to decide whether implants
      or fat graft are actually required as a secondary procedure.

PMID- 28497024
TI  - Decisional pathways in breast augmentation: how to improve outcomes through
      accurate pre-operative planning.
AB  - Breast augmentation is the most commonly performed surgical procedure in
      aesthetic plastic surgery. Accurate pre-operative planning is crucial to obtain
      the best outcomes. We present our planning method deriving from a more than 30
      year experience in aesthetic breast surgery, matching together patients tissues'
      characteristics and patients' wishes. We schematized our planning method in an
      easy-to-use flow diagram to help the decisional process in breast augmentation.

PMID- 28497025
TI  - How to prevent complications in breast augmentation.
AB  - No high-level evidences about the best technique or the best implant to use for
      obtaining the best outcomes in aesthetic breast augmentation, with low
      complications and re-interventions rates exist from available literature. In this
      paper we present the actual best evidence about the etiopathogenesis of main
      complications in aesthetic breast augmentation, identifying some basic rules to
      follow in order to reduce complication rates in our daily activity, minimizing re
      interventions, obtaining long lasting results and high women's satisfaction
      levels.

PMID- 28497026
TI  - CHCHD4 Regulates Intracellular Oxygenation and Perinuclear Distribution of
      Mitochondria.
AB  - Hypoxia is a characteristic of the tumor microenvironment and is known to
      contribute to tumor progression and treatment resistance. Hypoxia-inducible
      factor (HIF) dimeric transcription factors control the cellular response to
      reduced oxygenation by regulating the expression of genes involved in metabolic
      adaptation, cell motility, and survival. Alterations in mitochondrial metabolism
      are not only a downstream consequence of HIF-signaling but mitochondria
      reciprocally regulate HIF signaling through multiple means, including oxygen
      consumption, metabolic intermediates, and reactive oxygen species generation.
      CHCHD4 is a redox-sensitive mitochondrial protein, which we previously identified
      and showed to be a novel regulator of HIF and hypoxia responses in tumors.
      Elevated expression of CHCHD4 in human tumors correlates with the hypoxia gene
      signature, disease progression, and poor patient survival. Here, we show that
      either long-term (72 h) exposure to hypoxia (1% O2) or elevated expression of
      CHCHD4 in tumor cells in normoxia leads to perinuclear accumulation of
      mitochondria, which is dependent on the expression of HIF-1alpha. Furthermore, we
      show that CHCHD4 is required for perinuclear localization of mitochondria and HIF
      activation in response to long-term hypoxia. Mutation of the functionally
      important highly conserved cysteines within the Cys-Pro-Cys motif of CHCHD4 or
      inhibition of complex IV activity (by sodium azide) redistributes mitochondria
      from the perinuclear region toward the periphery of the cell and blocks HIF
      activation. Finally, we show that CHCHD4-mediated perinuclear localization of
      mitochondria is associated with increased intracellular hypoxia within the
      perinuclear region and constitutive basal HIF activation in normoxia. Our study
      demonstrates that the intracellular distribution of the mitochondrial network is
      an important feature of the cellular response to hypoxia, contributing to hypoxic
      signaling via HIF activation and regulated by way of the cross talk between
      CHCHD4 and HIF-1alpha.

PMID- 28497027
TI  - Data-Based Radiation Oncology: Design of Clinical Trials in the Toxicity
      Biomarkers Era.
AB  - The ability to stratify patients using a set of biomarkers, which predict that
      toxicity risk would allow for radiotherapy (RT) modulation and serve as a
      valuable tool for precision medicine and personalized RT. For patients presenting
      with tumors with a low risk of recurrence, modifying RT schedules to avoid
      toxicity would be clinically advantageous. Indeed, for the patient at low risk of
      developing radiation-associated toxicity, use of a hypofractionated protocol
      could be proposed leading to treatment time reduction and a cost-utility
      advantage. Conversely, for patients predicted to be at high risk for toxicity,
      either a more conformal form or a new technique of RT, or a multidisciplinary
      approach employing surgery could be included in the trial design to avoid or
      mitigate RT when the potential toxicity risk may be higher than the risk of
      disease recurrence. In addition, for patients at high risk of recurrence and low
      risk of toxicity, dose escalation, such as a greater boost dose, or irradiation
      field extensions could be considered to improve local control without severe
      toxicities, providing enhanced clinical benefit. In cases of high risk of
      toxicity, tumor control should be prioritized. In this review, toxicity
      biomarkers with sufficient evidence for clinical testing are presented. In
      addition, clinical trial designs and predictive models are described for
      different clinical situations.

PMID- 28497028
TI  - Inactive Gingipains from P. gingivalis Selectively Skews T Cells toward a Th17
      Phenotype in an IL-6 Dependent Manner.
AB  - Gingipain cysteine proteases are considered key virulence factors of
      Porphyromonas gingivalis. They significantly influence antibacterial and
      homeostatic functions of macrophages, neutrophils, the complement system, and
      cytokine networks. Recent data indicate the role of P. gingivalis in T cell
      differentiation; however, the involvement of gingipains in this process remains
      elusive. Therefore, the aim of this study was to investigate the contribution of
      danger signals triggered by the gingipains on the generation of Th17 cells, which
      play a key role in protection against bacterial diseases but may cause chronic
      inflammation and bone resorption. To this end we compared the effects of the wild
      type strain of P. gingivalis (W83) with its isogenic mutant devoid of gingipain
      activity (DeltaKDeltaRAB), and bacterial cells pretreated with a highly-specific
      inhibitor of gingipains activity (KYTs). Antigen presenting cells (APCs), both
      professional (dendritic cells), and non-professional (gingival keratinocytes),
      exposed to viable bacteria expressed high amounts of cytokines (IL-6, IL-21, IL
      23). These cytokines are reported to either stimulate or balance the Th17
      dependent immune response. Surprisingly, cells infected with P. gingivalis devoid
      of gingipain activity showed increased levels of all tested cytokines compared to
      bacteria with fully active enzymes. The effect was dependent on both the
      reduction of cytokine proteolysis and the lack of cross-talk with other bacterial
      virulence factors, including LPS and fimbriae that induce de novo synthesis of
      cytokines. The profile of lymphocyte T differentiation from naive T cells showed
      enhanced generation of Th17 in response to bacteria with inactive gingipains.
      Moreover, we found that gingipain-dependent induction of Th17 cells was highly
      specific, since other T cell-subsets remained unchanged. Finally, inhibition of
      IL-6 signaling in dendritic cells led to a significant depletion of the Th17
      population. Cumulatively, this study revealed a previously undisclosed role of
      gingipain activity in the process of Th17 differentiation reliant on blocking
      signaling through IL-6. Since inactivation of gingipains accelerates the skewing
      of T cells toward Th17 cells, which are detrimental in periodontitis, IL-6
      signaling may serve as an attractive target for treatment of the disease.

PMID- 28497031
TI  - The comparative study of resonance disorders for Vietnamese and Korean cleft
      palate speakers using nasometer.
AB  - BACKGROUND: Nasalance is used to evaluate the velopharyngeal incompetence in
      clinical diagnoses using a nasometer. The aim of this study is to find the
      nasalance differences between Vietnamese cleft palate children and Korean cleft
      palate children by measuring the nasalance of five oral vowels. METHODS: Ten
      Vietnamese cleft palate children after surgery, three Vietnamese children for the
      control group, and ten Korean cleft palate children after surgery with the same
      age participated in this experimentation. Instead of Korean control, the standard
      value of Korean version of the simplified nasometric assessment procedures
      (kSNAP) was used. RESULT: The results are as follows: (1) the highest nasalance
      score among the Vietnamese normal vowels is the low vowel /a/; however, that of
      Korean normal vowels is the high vowel /i/. (2) The average nasalance score of
      Korean cleft palate vowels is 18% higher than that of Vietnamese cleft palate
      vowels. There was a nasalance score of over 45% among the vowels /e/ and /i/ in
      Vietnamese cleft palate patients and /i/, /o/, and /u/ in Korean cleft palate
      patients. CONCLUSION: These different nasalance scores of the same vowels seem to
      cause an ethnic difference between Vietnamese and Korean cleft palate children.

PMID- 28497032
TI  - A Tribute to Bernardo Ochoa, MD.

PMID- 28497029
TI  - Reciprocal Interactions between Nematodes and Their Microbial Environments.
AB  - Parasitic nematode infections are widespread in nature, affecting humans as well
      as wild, companion, and livestock animals. Most parasitic nematodes inhabit the
      intestines of their hosts living in close contact with the intestinal microbiota.
      Many species also have tissue migratory life stages in the absence of severe
      systemic inflammation of the host. Despite the close coexistence of helminths
      with numerous microbes, little is known concerning these interactions. While the
      environmental niche is considerably different, the free-living nematode
      Caenorhabditis elegans (C. elegans) is also found amongst a diverse microbiota,
      albeit on decaying organic matter. As a very well characterized model organism
      that has been intensively studied for several decades, C. elegans interactions
      with bacteria are much more deeply understood than those of their parasitic
      counterparts. The enormous breadth of understanding achieved by the C. elegans
      research community continues to inform many aspects of nematode parasitology.
      Here, we summarize what is known regarding parasitic nematode-bacterial
      interactions while comparing and contrasting this with information from work in
      C. elegans. This review highlights findings concerning responses to bacterial
      stimuli, antimicrobial peptides, and the reciprocal influences between nematodes
      and their environmental bacteria. Furthermore, the microbiota of nematodes as
      well as alterations in the intestinal microbiota of mammalian hosts by helminth
      infections are discussed.

PMID- 28497033
TI  - Intrapulmonary Percussive Ventilation as an Airway Clearance Technique during
      Venoarterial Extracorporeal Life Support in an Infant with Pertussis.
AB  - Initiation of extracorporeal life support (ECLS) is often followed by complete
      opacification of pulmonary parenchyma and volume loss. The optimal mechanical
      ventilator management and lung recruitment strategy of a pediatric patient
      requiring extracorporeal membrane oxygenation is not known. We present a case of
      a 4-week old infant who developed a severe pertussis infection requiring ECLS.
      The severity of his illness and pertussis infection-associated intraluminal
      bronchiole obstruction made medical management challenging. In addition to lung
      protection ventilator strategies and bronchoscopy, intrapulmonary percussive
      ventilation was initiated to facilitate lung recruitment. This was associated
      with precipitous incremental improvement in lung compliance and eventual
      liberation from venoarterial ECLS.

PMID- 28497030
TI  - FDA-approved immunosuppressants targeting staphylococcal superantigens:
      mechanisms and insights.
AB  - Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic
      toxins cause diseases in human beings and laboratory animals by hyperactivating
      cells of the immune system. These protein toxins bind to the major
      histocompatibility complex class II (MHC II) molecules and specific Vbeta regions
      of T-cell receptors (TCRs), resulting in the stimulation of both
      monocytes/macrophages and T lymphocytes. The bridging of TCR with MHC II
      molecules by superantigens triggers intracellular signaling cascades, resulting
      in excessive release of proinflammatory mediators and massive polyclonal T-cell
      proliferation. The early induction of tumor necrosis factor alpha, interleukin 1
      (IL-1), interleukin 2 (IL-2), interferon gamma (IFNgamma), and macrophage
      chemoattractant protein 1 promotes fever, inflammation, and multiple organ
      injury. The signal transduction pathways for staphylococcal superantigen-induced
      toxicity downstream from TCR/major histocompatibility complex (MHC) ligation and
      interaction of cell surface co-stimulatory molecules include the mitogen
      activated protein kinase cascades and cytokine receptor signaling, activating
      nuclear factor kappaB (NFkappaB) and the phosphoinositide 3-kinase/mammalian
      target of rapamycin pathways. Knowledge of host regulation within these activated
      pathways and molecules initiated by SEB and other superantigens enables the
      selection of US Food and Drug Administration (FDA)-approved drugs to interrupt
      and prevent superantigen-induced shock in animal models. This review focuses on
      the use of FDA-approved immunosuppressants in targeting the signaling pathways
      induced by staphylococcal superantigens.

PMID- 28497034
TI  - Comparison of Fluoride Levels in Tap and Bottled Water and Reported Use of
      Fluoride Supplementation in a United States-Mexico Border Community.
AB  - BACKGROUND: Compared to the general United States (U.S.) population, Arizona
      counties along the U.S.-Mexico border have a higher prevalence of dental caries,
      which can be reduced with adequate fluoride exposure. Because of concern
      regarding local tap water quality, fluoride-free bottled water consumption is
      common in this region, raising concern that families are not receiving adequate
      fluoride to promote dental health. OBJECTIVE: To evaluate the levels of fluoride
      in tap and bottled water as well as the use of fluoride supplements in an Arizona
      border community. METHODS: Low-income Latino households (n = 90) who report use
      of bottled water as their primary source of water intake were recruited.
      Participants completed a questionnaire about their and their children's dental
      histories and use of fluoride supplements. Water samples (bottled and tap) were
      collected from a subset of households (n = 30) for analysis of fluoride. RESULTS:
      Fluoride detection levels were significantly greater (p = 0.02, Fisher's exact
      test) in tap water (average = 0.49 mg/dL) than in bottled water, yet, the
      majority (22/30) were below the range for optimal dental health (0.7-1.2 mg/L).
      Concentration of fluoride in the majority (29/30) of bottled water samples was
      below the quantitative detection limit of 0.4 mg/L. Children were significantly
      less likely to have dental caries if they received fluoride varnishing treatments
      (p = 0.01, Fisher's exact test), lived in households that reported using
      fluoridated mouthwash (p < 0.001, Fisher's exact test), their parents received
      fluoride education (p = 0.01, Fisher's exact test), and their parents reported
      visiting a dentist yearly (p < 0.001, Fisher's exact test). Furthermore, none of
      the participants reported receiving recommendations from health-care providers
      about fluoride supplementation or variance in content by the type of water
      consumed. CONCLUSION: Although fluoride was significantly more likely to be
      detected in tap than bottled water, neither water source in this border community
      is likely to provide enough fluoride for optimal dental health. Low-income
      children in this region may benefit from regular access to fluoride varnishing
      treatments and/or use of fluoridated mouthwash, interventions that could be
      tested in future well-designed trials.

PMID- 28497035
TI  - Postpartum Depressive Symptoms and Associated Factors in Married Women: A Cross
      sectional Study in Danang City, Vietnam.
AB  - INTRODUCTION: Postpartum depression (PPD) among women is a common mental health
      concern. It occurs at a time of major life change, coupled with the increased
      responsibilities associated with the care of a newborn infant. In Vietnam, the
      prevalence of depressive symptoms after giving birth has not been fully
      investigated. Research in the Northern provinces, in Ho Chi Minh City, and in Hue
      suggests postnatal depressive symptoms among women are common. This research aims
      to (1) estimate the prevalence of PPD symptoms among married women in one Vietnam
      city (Danang) and (2) identify the social and personal factors associated with
      postpartum depressive symptoms. METHODS: This cross-sectional study was conducted
      from July 2013 to August 2014 in 10 wards of Hai Chau District, Danang. A total
      of 600 mothers who gave birth 4 weeks to 6 months prior to being interviewed were
      recruited. Interviews were conducted using structured questionnaires, which
      included several dimensions: demographics, family living arrangements,
      expectations of pregnancy, expectations of infant gender, the woman's
      relationship with her husband, exercise after birth, infant health, and anxiety
      about matters other than the birth. The Edinburgh Postpartum Depression Scale
      (EPDS) was used to examine PPD symptoms, with a cutoff point of 12/13. RESULTS:
      EPDS scores indicated the prevalence of PPD symptoms was 19.3% (95% CI: 16.16
      22.50). Among women with PPD symptoms, 37.9% had suicidal thoughts in the
      previous seven days. Multivariate logistic regression indicated that the
      following key factors were significantly associated with PPD symptoms: Not being
      able to rely on their husband for help, having a husband who does not spend time
      to discuss problems, having anxiety about matters other than the birth, not
      exercising after giving birth, and having an ill baby. CONCLUSION: These findings
      should be interpreted in relation to other recent research in Vietnam. A
      consistent pattern of prevalence estimates and associated social factors is
      emerging that has implications for the postpartum care of mothers.

PMID- 28497036
TI  - Reversed Phase HPLC-DAD Profiling of Carotenoids, Chlorophylls and Phenolic
      Compounds in Adiantum capillus-veneris Leaves.
AB  - Adiantum capillus-veneris is important endangered fern species with several
      medicinal properties. In this study, the leaves samples were extracted and
      separated using reversed phase HPLC with DAD for carotenoids, chlorophylls and
      phenolic compounds. Separation of carotenoids and chlorophylls were carried out
      using a tertiary gradient system of water, MTBE and methanol-water, while a
      binary gradient system of methanol-water-acetic acid was used for phenolic
      profiling. Results revealed eight carotenoids, four pheophytins, and two
      chlorophylls. Lutein (806.0 MUg/g), chlorophyll b' (410.0 MUg/g), chlorophyll a
      (162.4 MUg/g), 9'-Z-neoxanthin (142.8 MUg/g) and all-E-violaxanthin (82.2 MUg/g)
      were present in higher amounts. The relatively high amounts of lutein may be one
      of the key indicator of beneficial antioxidant properties. The phenolic profile
      revealed a total of 13 compounds, namely 4-hydroxybenzoic acid, chlorogenic acid,
      caftaric acid, kaempferol glycosides, p-coumaric acid, rosmarinic acid, 5
      caffeoylquinic acid, and quercetin glycosides. Kaempferol-3-sophorotrioside (58.7
      mg/g), chlorogenic acid (28.5 mg/g), 5-O-caffeoylquinic acid (18.7 mg/g),
      coumaric acid (11.2 mg/g), and its derivative (33.1 mg/g) were present in high
      amounts. These results suggest that the reversed phase HPLC profiling of Adiantum
      leaves provides a better understanding in to the actual composition of bioactive
      compounds, which may be responsible for the potential medicinal properties.
      Adiantum leaves rich in important bioactive phytochemicals can be used as a
      possible source of nutraceuticals or as a functional food ingredient.

PMID- 28497037
TI  - Timeliness of Operating Room Case Planning and Time Utilization: Influence of
      First and To-Follow Cases.
AB  - Resource and cost constraints in hospitals demand thorough planning of operating
      room schedules. Ideally, exact start times and durations are known in advance for
      each case. However, aside from the first case's start, most factors are hard to
      predict. While the role of the start of the first case for optimal room
      utilization has been shown before, data for to-follow cases are lacking. The
      present study therefore aimed to analyze all elective surgery cases of a
      university hospital within 1 year in search of visible patterns. A total of
      14,014 cases scheduled on 254 regular working days at a university hospital
      between September 2015 and August 2016 underwent screening. After eliminating 112
      emergencies during regular working hours, 13,547 elective daytime cases were
      analyzed, out of which 4,346 ranked first, 3,723 second, and 5,478 third or
      higher in the daily schedule. Also, 36% of cases changed start times from the day
      before to 7:00 a.m., with half of these (52%) resulting in a delay of more than
      15 min. After 7:00 a.m., 87% of cases started more than 10 min off schedule, with
      26% being early and 74% late. Timeliness was 15 +/- 72 min (mean +/- SD) for
      first, 21 +/- 84 min for second, and 25 +/- 93 min for all to-follow cases,
      compared to preoperative day planning, and 21 +/- 45, 23 +/- 61, and 19 +/- 74
      min compared to 7:00 a.m. status. Start time deviations were also related to
      procedure duration, with cases of 61-90 min duration being most reliable
      (deviation 9.8 +/- 67 min compared to 7:00 a.m.), regardless of order. In
      consequence, cases following after 61-90 min long cases had the shortest
      deviations of incision time from schedule (16 +/- 66 min). Taken together, start
      times for elective surgery cases deviate substantially from schedule, with first
      and second cases falling into the highest mean deviation category. Second cases
      had the largest deviations from scheduled times compared to first and all to
      follow cases. While planned vs. actual start times differ among specialties,
      cases of 61-90 min duration had the most reliable start times, with neither
      shorter nor longer cases seeming to improve timeliness of start times.

PMID- 28497038
TI  - Epigenetics and Vascular Diseases: Influence of Non-coding RNAs and Their
      Clinical Implications.
AB  - Epigenetics refers to heritable mechanisms able to modulate gene expression that
      do not involve alteration of the genomic DNA sequence. Classically, mechanisms
      such as DNA methylation and histone modifications were part of this
      classification. Today, this field of study has been expanded and includes also
      the large class of non-coding RNAs (ncRNAs). Indeed, with the extraordinary
      possibilities introduced by the next-generation sequencing approaches, our
      knowledge of the mammalian transcriptome has greatly improved. Today, we have
      identifying thousands of ncRNAs, and unsurprisingly, a direct association between
      ncRNA dysregulation and development of cardiovascular pathologies has been
      identified. This class of gene modulators is further divided into short-ncRNAs
      and long-non-coding RNAs (lncRNAs). Among the short-ncRNA sub-group, the best
      characterized players are represented by highly conserved RNAs named microRNAs
      (miRNAs). miRNAs principally inhibit gene expression, and their involvement in
      cardiovascular diseases has been largely studied. On the other hand, due to the
      different roles played by lncRNAs, their involvement in cardiovascular pathology
      development is still limited, and further studies are needed. For instance, in
      order to define their roles in the cellular processes associated with the
      development of diseases, we need to better characterize the details of their
      mechanisms of action; only then might we be able to develop innovative
      therapeutic strategies. In this review, we would like to give an overview of the
      current knowledge on the function of ncRNAs and their involvement in the
      development of vascular diseases.

PMID- 28497039
TI  - High Glucose Promotes CD36 Expression by Upregulating Peroxisome Proliferator
      Activated Receptor gamma Levels to Exacerbate Lipid Deposition in Renal Tubular
      Cells.
AB  - Diabetic kidney disease (DKD) appears to be closely related to lipid deposition
      in kidney. The aim of this study was to determine whether high glucose (HG)
      exacerbated lipid deposition by increasing CD36 expression via AKT-PPARgamma
      signaling pathway. Our results showed that HG activated AKT signaling pathway,
      followed by an increase in PPARgamma that induced CD36 overexpression, ultimately
      causing lipid deposition in HK-2 cells. We also found that inhibition of AKT
      PPARgamma signaling pathway or knockdown of CD36 could reduce HG-induced lipid
      accumulation in HK-2 cells. These results indicated that AKT-PPARgamma signaling
      pathway mediated HG-induced lipid deposition by upregulating CD36 expression in
      HK-2 cells and that inhibition of AKT-PPARgamma signaling pathway had the
      potential beneficial effects of reducing lipid deposition in diabetic kidney.

PMID- 28497040
TI  - Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in
      Wistar Rats.
AB  - Increased sugar consumption, especially fructose, is strongly related to the
      development of type 2 diabetes (T2D) and metabolic syndrome. The aim of this
      study was to evaluate long term effects of fructose supplementation on Wistar
      rats. Three-week-old male rats were randomly divided into 2 groups: control (C; n
      = 14) and fructose fed (FF; n = 18), with a fructose enriched drink (20-25% w/v
      fructose in water) for 21 weeks. Systolic blood pressure, fasting glycemia, and
      bodyweight were regularly measured. Glucose tolerance was evaluated three times
      using an oral glucose tolerance test. Insulin levels were measured concomitantly
      and insulin resistance markers were evaluated (HOMA 2-IR, Insulin Sensitivity
      Index for glycemia (ISI-gly)). Lipids profile was evaluated on plasma. This
      fructose supplementation resulted in the early induction of hypertension without
      renal failure (stable theoretical creatinine clearance) and in the progressive
      development of fasting hyperglycemia and insulin resistance (higher HOMA 2-IR,
      lower ISI-gly) without modification of glucose tolerance. FF rats presented
      dyslipidemia (higher plasma triglycerides) and early sign of liver malfunction
      (higher liver weight). Although abdominal fat weight was increased in FF rats, no
      significant overweight was found. In Wistar rats, 21 weeks of fructose
      supplementation induced a metabolic syndrome (hypertension, insulin resistance,
      and dyslipidemia) but not T2D.

PMID- 28497041
TI  - Annexin A3 as a Prognostic Biomarker for Breast Cancer: A Retrospective Study.
AB  - To validate the correlation between ANXA3 expression and prognosis in breast
      cancer, a retrospective study encompassing 309 breast cancer patients was
      performed. The expression of ANXA3 was determined by the immunohistochemical
      examination of tissue sections by the Max VisionTM method. The ANXA3 levels in
      the patient samples were validated for the prognosis based on age, menopause
      status, tumor size, tumor node, metastasis stage, the number of lymphatic
      metastases, oncology grade, and molecular subtyping. An elevated expression of
      ANXA3 was detected in breast cancer samples, compared to adjacent tissue samples,
      and significant correlation depending on the number of lymphatic metastases (P =
      0.001) and histological grade (P = 0.004) was observed. The number of lymphatic
      metastases and ANXA3 expression were identified as independent risk factors
      affecting the disease-free survival and overall survival. Significantly (P <
      0.002) higher level of ANXA3 was detected in triple-negative breast cancer
      compared to other subtypes. There was no significant (P > 0.05) change in the
      expression of ANXA3 with respect to age, menopausal status, tumor size, and
      clinical stage. The findings implicate the expression of ANXA3 with the natural
      progression of breast cancer and associate it with increased lymphatic
      metastasis. The study validates the use of ANXA3 as a potential prognosis
      biomarker for breast cancer.

PMID- 28497042
TI  - Scientific Evidence for Different Options for GDM Screening and Management:
      Controversies and Review of the Literature.
AB  - Background. Gestational diabetes (GDM) affects up to 7% of pregnant women and is
      associated with several maternal and perinatal morbidities. International
      organizations suggest several different recommendations regarding how to screen
      and to manage GDM. Objective. We aimed to analyze the most important and employed
      guidelines about screening and management of GDM and we investigated existing
      related literature. Results. We found several different criteria for screening
      for GDM, for monitoring GDM, and for starting pharmacological therapy. When using
      IADPSG criteria, GDM rate increased, perinatal outcomes improved, and screening
      became cost-effective. Compared to no treatment, treatment of women meeting
      criteria for GDM by IADPSG criteria but not by other less strict criteria has
      limited evidence for an effect on adverse pregnancy outcomes.

PMID- 28497043
TI  - The Effect of Different Pollination on the Expression of Dangshan Su Pear
      MicroRNA.
AB  - The high-throughput sequencing of pear "Dangshan Su" * "Yali" (whose fruits
      lignin and stone cell content are high and quality is poor) and pear "Dangshan
      Su" * "Wonhwang" (whose fruits with low content of lignin and stone cell and the
      quality are better ) found that the expressions of these two miRNAs (pyr-1809 and
      pyr-novel-miR-144-3p) were significantly different; their corresponding target
      genes encode two kinds of laccase (Pbr018935.1 and Pbr003857.1). qRT-PCR results
      showed that these two enzymes are involved in the formation of lignin and stone
      cells and the existence of these two miRNAs has a negative effect on them. It was
      concluded that the effect of pollination on the development of stone cells may
      affect the synthesis of lignin, through the regulation of laccase controlled by
      miRNAs, and ultimately affect the formation of stone cell and fruit quality.

PMID- 28497044
TI  - Predicting the Types of Ion Channel-Targeted Conotoxins Based on AVC-SVM Model.
AB  - The conotoxin proteins are disulfide-rich small peptides. Predicting the types of
      ion channel-targeted conotoxins has great value in the treatment of chronic
      diseases, epilepsy, and cardiovascular diseases. To solve the problem of
      information redundancy existing when using current methods, a new model is
      presented to predict the types of ion channel-targeted conotoxins based on AVC
      (Analysis of Variance and Correlation) and SVM (Support Vector Machine). First,
      the F value is used to measure the significance level of the feature for the
      result, and the attribute with smaller F value is filtered by rough selection.
      Secondly, redundancy degree is calculated by Pearson Correlation Coefficient. And
      the threshold is set to filter attributes with weak independence to get the
      result of the refinement. Finally, SVM is used to predict the types of ion
      channel-targeted conotoxins. The experimental results show the proposed AVC-SVM
      model reaches an overall accuracy of 91.98%, an average accuracy of 92.17%, and
      the total number of parameters of 68. The proposed model provides highly useful
      information for further experimental research. The prediction model will be
      accessed free of charge at our web server.

PMID- 28497045
TI  - High Rate of Deformed Larvae among Gynogenetic Brown Trout (Salmo trutta m.
      fario) Doubled Haploids.
AB  - Mitotic gynogenesis results in the production of fully homozygous individuals in
      a single generation. Since inbred fish were found to exhibit an increased
      frequency of body deformations that may affect their survival, the main focus of
      this research was to evaluate the ratio of individuals with spinal deformities
      among gynogenetic doubled haploids (DHs) brown trout as compared to
      nonmanipulated heterozygous individuals. Gynogenetic development was induced by
      the activation of brown trout eggs by UV-irradiated homologous and heterologous
      (rainbow trout) spermatozoa. The subsequent exposure of the activated eggs to the
      high hydrostatic pressure disturbed the first cleavage in gynogenetic zygotes and
      enabled duplication of the maternal haploid set of chromosomes. The survival rate
      was significantly higher among gynogenetic brown trout hatched from eggs
      activated with the homologous UV-irradiated spermatozoa when compared to DHs
      hatched from eggs activated by the heterologous spermatozoa. More than 35% of the
      gynogenetic larvae exhibited body deformities, mostly lordosis and scoliosis. The
      percentage of malformed brown trout from the control group did not exceed 15%.
      The increased number of deformed larvae among DHs brown trout suggested rather a
      genetic background of the disease related to the fish spine deformities; however,
      both genetic and environmental factors were discussed as a cause of such
      conditions in fish.

PMID- 28497046
TI  - Corrigendum to "Quantitative Evaluation and Selection of Reference Genes for
      Quantitative RT-PCR in Mouse Acute Pancreatitis".
AB  - [This corrects the article DOI: 10.1155/2016/8367063.].

PMID- 28497047
TI  - Association Study of Gut Flora in Coronary Heart Disease through High-Throughput
      Sequencing.
AB  - Objectives. We aimed to explore the impact of gut microbiota in coronary heart
      disease (CHD) patients through high-throughput sequencing. Methods. A total of 29
      CHD in-hospital patients and 35 healthy volunteers as controls were included.
      Nucleic acids were extracted from fecal samples, followed by alpha diversity and
      principal coordinate analysis (PCoA). Based on unweighted UniFrac distance
      matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were
      created. Results. After data optimization, an average of 121312 +/- 19293 reads
      in CHD patients and 234372 +/- 108725 reads in controls was obtained. Reads
      corresponding to 38 phyla, 90 classes, and 584 genera were detected in CHD
      patients, whereas 40 phyla, 99 classes, and 775 genera were detected in controls.
      The proportion of phylum Bacteroidetes (56.12%) was lower and that of phylum
      Firmicutes was higher (37.06%) in CHD patients than those in the controls (60.92%
      and 32.06%, P < 0.05). PCoA and UPGMA tree analysis showed that there were
      significant differences of gut microbial compositions between the two groups.
      Conclusion. The diversity and compositions of gut flora were different between
      CHD patients and healthy controls. The incidence of CHD might be associated with
      the alteration of gut microbiota.

PMID- 28497048
TI  - Antimicrobial Resistance Patterns in Women with Positive Urine Culture: Does
      Menopausal Status Make a Significant Difference?
AB  - Aim. Urinary tract infection (UTI) is considered one of the most common bacterial
      infections in women. The aim of this study was to investigate the types of
      uropathogens present, as well as the degree of antimicrobial drug resistance seen
      among premenopausal (n = 2748) and postmenopausal (n = 1705) women with
      uncomplicated UTI. Methods. Urinary samples (n = 4453) collected from women with
      UTI were analyzed in terms of uropathogens present. These were considered as
      positive if bacterial growth was >=105 colony forming units (CFUs)/mL.
      Susceptibility and resistance testing for commonly used antibiotics was
      subsequently assessed. Results. The most common uropathogens cultured from urine
      samples were Escherichia coli (65.5%), followed by Enterococcus faecalis (12.2%),
      Klebsiella pneumoniae (4.7%), and Proteus mirabilis (4.2%). The resistance to
      ampicillin exceeded 40%, independently of menopausal status. Of note, resistance
      to ciprofloxacin exceeded 25% among postmenopausal patients. Moreover, resistance
      of all uropathogens to commonly used antimicrobials was significantly higher in
      postmenopausal women. Conclusion. Due to the high resistance rate, ampicillin,
      ciprofloxacin, and the trimethoprim/sulfamethoxazole combination should be
      avoided in treating postmenopausal women affected by UTI without being indicated
      by initial urine culture report. Finally, cephalexin and cefuroxime are promising
      alternatives as initial treatment in postmenopausal women.

PMID- 28497049
TI  - Biomechanical Analysis of Cuboid Osteotomy Lateral Column Lengthening for Stage
      II B Adult-Acquired Flatfoot Deformity: A Cadaveric Study.
AB  - Purpose. To investigate the effect of cuboid osteotomy lateral column lengthening
      (LCL) for the correction of stage II B adult-acquired flatfoot deformity in
      cadaver. Methods. Six cadaver specimens were loaded to 350 N. Flatfoot models
      were established and each was evaluated radiographically and pedobarographically
      in the following conditions: (1) intact foot, (2) flatfoot, and (3) cuboid
      osteotomy LCL (2, 3, 4, and 5 mm). Results. Compared with the flatfoot model, the
      LCLs showed significant correction of talonavicular coverage on anteroposterior
      radiographs and talus-first metatarsal angle on both anteroposterior and lateral
      radiographs (p < .05). Compared with the intact foot, the above angles of the
      LCLs showed no significant difference except the 2 mm LCL. In terms of forefoot
      pressure, medial pressure of the 2 mm LCL (p = .044) and lateral pressure of the
      3, 4, and 5 mm LCLs showed statistical differences (p < .05), but lateral
      pressure of the 3 mm LCL was not more than the intact foot as compared to the 4
      and 5 mm LCLs, which was less than medial pressure. Conclusion. Cuboid osteotomy
      LCL procedure avoids damage to subtalar joint and has a good effect on correction
      of stage II B adult-acquired flatfoot deformity with a 3 mm lengthening in
      cadavers.

PMID- 28497050
TI  - The Role of Biologically Active Ingredients from Natural Drug Treatments for
      Arrhythmias in Different Mechanisms.
AB  - Arrhythmia is a disease that is caused by abnormal electrical activity in the
      heart rate or rhythm. It is the major cause of cardiovascular morbidity and
      mortality. Although several antiarrhythmic drugs have been used in clinic for
      decades, their application is often limited by their adverse effects. As a
      result, natural drugs, which have fewer side effects, are now being used to treat
      arrhythmias. We searched for all articles on the role of biologically active
      ingredients from natural drug treatments for arrhythmias in different mechanisms
      in PubMed. This study reviews 19 natural drug therapies, with 18 active
      ingredient therapies, such as alkaloids, flavonoids, saponins, quinones, and
      terpenes, and two kinds of traditional Chinese medicine compound (Wenxin-Keli and
      Shensongyangxin), all of which have been studied and reported as having
      antiarrhythmic effects. The primary focus is the proposed antiarrhythmic
      mechanism of each natural drug agent. Conclusion. We stress persistent vigilance
      on the part of the provider in discussing the use of natural drug agents to
      provide a solid theoretical foundation for further research on antiarrhythmia
      drugs.

PMID- 28497051
TI  - MicroRNA Expression Signature in Human Calcific Aortic Valve Disease.
AB  - Altered microRNA (miRNA, miR) expression has been related to many disease
      processes; however, the miRNA expression signature in calcific aortic valve
      disease (CAVD) is unclear. In this study, microarrays were used to determine the
      miRNA expression signature of tissue samples from healthy individuals (n = 4) and
      patients with CAVD (n = 4). TargetScan, PITA, and microRNAorg 3-way databases
      were used to predict the potential target genes. DIANA-miRPath was used to
      incorporate the aberrant miRNAs into gene pathways. miRNA microarrays identified
      92 differentially expressed miRNAs in CAVD tissues. The principal component
      analysis (PCA) of these samples and the unsupervised hierarchical clustering
      analysis based on the 92 aberrantly expressed miRNAs noted that miRNA expression
      could be categorized into two well-defined clusters that corresponded to healthy
      control and CAVD. Bioinformatic analysis showed the miRNA targets and potential
      molecular pathways. Collectively, our study reported the miRNA expression
      signature in CAVD and may provide potential therapeutic targets for CAVD.

PMID- 28497052
TI  - Etiological and Resistance Profile of Bacteria Involved in Urinary Tract
      Infections in Young Children.
AB  - Background. The objective of this study was to identify the bacteria most
      frequently responsible for urinary tract infection (UTI) in the population of
      under-2-year-olds in our geographic area and to evaluate the activity of
      antibiotics widely used for UTI treatment during a 4-year study period. Materials
      and Methods. A retrospective analysis was conducted of data on the identification
      and susceptibility of microorganisms isolated in urine samples from children
      under 2 years of age. Results. A total of 1,045 uropathogens were isolated.
      Escherichia coli accounted for the majority (60.3%) of these, followed by
      Enterococcus faecalis (22.4%) and Klebsiella spp. (6.5%). The highest E. coli
      susceptibility rates (>90%) were to piperacillin-tazobactam, cefuroxime,
      cefotaxime, ceftazidime, imipenem, gentamicin, nitrofurantoin, and fosfomycin,
      and the lowest were to amoxicillin-clavulanic acid and cotrimoxazole. Among all
      bacteria isolated, we highlight the overall high activity of piperacillin
      tazobactam, imipenem, nitrofurantoin, and fosfomycin against both community and
      hospital isolates and the reduced activity of amoxicillin-clavulanic acid,
      cephalosporins, gentamicin, and cotrimoxazole. There was no significant change in
      the total activity of any of the studied antibiotics over the 4-year study
      period. Conclusion. Empiric treatment with amoxicillin-clavulanic acid,
      cotrimoxazole, cephalosporins, and gentamicin may be inadequate due to their
      limited activity against uropathogens in our setting.

PMID- 28497053
TI  - Numerical Evaluation of Image Contrast for Thicker and Thinner Objects among
      Current Intraoral Digital Imaging Systems.
AB  - The purpose is to evaluate the performance of current intraoral digital detectors
      in detail using a precise phantom and new method. Two aluminum step wedges in 0.5
      mm steps were exposed by two photostimulable phosphor plate (PSP) systems-one
      with automatic exposure compensation (AEC) and the other without AEC-and a CCD
      sensor. Images were obtained with 3 doses at 60 kV. The effect of metallic
      material also was evaluated. The contrast-to-noise ratio (CNR) for thinner steps
      and the low contrast value (LCV) for thicker steps were obtained. The CCD system
      was the best under all conditions (P < 0.001), although the Gray value was
      sensitive to the dose, and the Gray value-dose relation varied greatly. The PSP
      system with AEC was superior to that without AEC for the LCV (P < 0.001) but was
      inferior to it regarding the CNR (P < 0.001). CNR and LCV in the PSP system
      without AEC were not affected by the metallic plate. Intraoral digital imaging
      systems should be chosen according to their diagnostic purpose. PSP system with
      AEC may be the best for detecting molar proximal caries, whereas the PSP system
      without AEC may be better for evaluating small bone regeneration in periodontal
      disease. The CCD system provided the best performance.

PMID- 28497054
TI  - Electrical Stimulation for Wound-Healing: Simulation on the Effect of Electrode
      Configurations.
AB  - Endogenous electric field is known to play important roles in the wound-healing
      process, mainly through its effects on protein synthesis and cell migration. Many
      clinical studies have demonstrated that electrical stimulation (ES) with steady
      direct currents is beneficial to accelerating wound-healing, even though the
      underlying mechanisms remain unclear. In the present study, a three-dimensional
      finite element wound model was built to optimize the electrode configuration in
      ES. Four layers of the skin, stratum corneum, epidermis, dermis, and subcutis,
      with defined thickness and electrical properties were modeled. The main goal was
      to evaluate the distributions of exogenous electric fields delivered with direct
      current (DC) stimulation using different electrode configurations such as sizes
      and positions. Based on the results, some guidelines were obtained in designing
      the electrode configuration for applications of clinical ES.

PMID- 28497055
TI  - Indigenous Wildlife Rabies in Taiwan: Ferret Badgers, a Long Term Terrestrial
      Reservoir.
AB  - The emerging disease of rabies was confirmed in Taiwan ferret badgers (FBs) and
      reported to the World Organization for Animal Health (OIE) on July 17, 2013. The
      spread of wildlife rabies can be related to neighborhood countries in Asia. The
      phylogenetic analysis was conducted by maximum likelihood (ML) methods and the
      Bayesian coalescent approach based on the glycoprotein (G) and nucleoprotein (N)
      genes. The phylogeographic and spatial temporal dynamics of viral transmission
      were determined by using SPREAD, QGIS. Therefore, the origin and the change with
      time of the viruses can be identified. Results showed the rabies virus of FB
      strains in Taiwan is a unique clade among other strains in Asia. According to the
      phylogeographic coalescent tree, three major genotypes of the FB rabies virus
      have circulated in three different geographical areas in Taiwan. Two genotypes
      have distributed into central and southern Taiwan between two ecological river
      barriers. The third genotype has been limited in southeastern Taiwan by the
      natural mountain barrier. The diversity of FB rabies viruses indicates that the
      biological profile of FBs could vary in different geographical areas in Taiwan.
      An enhanced surveillance system needs to be established near the currently
      identified natural barriers for early warnings of the rabies virus outbreak in
      Taiwan.

PMID- 28497056
TI  - Direction-Dependent Effects of Combined Static and ELF Magnetic Fields on Cell
      Proliferation and Superoxide Radical Production.
AB  - Proliferation of human umbilical vein endothelial cells was stimulated by a
      nearly vertical 60 or 120 MUT static magnetic field (MF) in comparison to cells
      that were shielded against MFs. When the static field was combined with an
      extremely low frequency (ELF) MF (18 Hz, 30 MUT), proliferation was suppressed by
      a horizontal but not by a vertical ELF field. As these results suggested that the
      effects of an ELF MF depend on its direction in relation to the static MF,
      independent experiments were carried out to confirm such dependence using 50 Hz
      MFs and a different experimental model. Cytosolic superoxide level in rat glioma
      C6 cells exposed in the presence of a nearly vertical 33 MUT static MF was
      increased by a horizontal 50 Hz, 30 MUT MF, but not affected by a vertical 50 Hz
      MF. The results suggest that a weak ELF MF may interact with the static
      geomagnetic field in producing biological effects, but the effect depends on the
      relative directions of the static and ELF MFs.

PMID- 28497057
TI  - Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and
      Muscle Loss in Early Stages of Disuse Atrophy.
AB  - The purpose of the present study is to investigate the effects of low-frequency
      electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size,
      capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the
      early stages of denervation-induced limb disuse. Direct ES was performed on the
      tibialis anterior muscle following denervation in seven-week-old male rats. The
      rats were divided into the following groups: control (CON), denervation (DN), and
      denervation with direct ES (DN + ES). Direct ES was performed at an intensity of
      16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week.
      We performed immunohistochemical staining to determine the expression of
      dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight,
      myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the
      tibialis anterior (TA) muscle were significantly reduced in the DN group compared
      to the control and DN + ES groups. The MMP-2 positive area was significantly
      greater in DN and DN + ES groups compared to the control group. These findings
      suggest beneficial effects of direct ES in reducing muscle atrophy and capillary
      regression without increasing MMP-2 immunoreactivity in the early stages of DN
      induced muscle disuse in rat hind limbs.

PMID- 28497058
TI  - Impact of an Intensive Perinatal Handwashing Promotion Intervention on Maternal
      Handwashing Behavior in the Neonatal Period: Findings from a Randomized
      Controlled Trial in Rural Bangladesh.
AB  - One-quarter of neonatal deaths are attributed to infections. Maternal handwashing
      with soap may prevent neonatal sepsis. We examined impact of intensive
      handwashing promotion on handwashing behavior of mothers of neonates. In Matlab,
      Bangladesh, we randomly allocated pregnant women at 28-32 weeks' gestation to
      intensive handwashing promotion or control. Behavior change communicators used a
      participatory approach to motivate maternal handwashing with soap and provided
      soap and handwashing stations. In the neonatal period, we observed soap and water
      at handwashing places and, at the end of the neonatal period, we estimated impact
      on maternal handwashing by structured observation. Among 253 women enrolled,
      intervention households were between 5.7 and 15.2 times as likely as control
      households to have soap and water present at the handwashing station in the
      baby's sleeping area. Intervention mothers washed hands with soap 4.1 times as
      frequently as controls (95% CI 2.55-6.59); handwashing with soap at recommended
      times was infrequent in both intervention (9%) and control (2%) groups.
      Intensively promoting handwashing with soap resulted in increased availability of
      soap and water at handwashing places, but only a modest increase in maternal
      handwashing with soap. Novel approaches to motivating handwashing behavior to
      protect newborns should be developed and evaluated.

PMID- 28497059
TI  - A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov
      Model.
AB  - The discovery of cis-regulatory modules (CRMs) is the key to understanding
      mechanisms of transcription regulation. Since CRMs have specific regulatory
      structures that are the basis for the regulation of gene expression, how to model
      the regulatory structure of CRMs has a considerable impact on the performance of
      CRM identification. The paper proposes a CRM discovery algorithm called ComSPS.
      ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the
      rules of CRM transcriptional grammar that governs the internal motif site
      arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it
      with five existing methods. Experimental results show that ComSPS performs better
      than them.

PMID- 28497061
TI  - Mining of Microbial Genomes for the Novel Sources of Nitrilases.
AB  - Next-generation DNA sequencing (NGS) has made it feasible to sequence large
      number of microbial genomes and advancements in computational biology have opened
      enormous opportunities to mine genome sequence data for novel genes and enzymes
      or their sources. In the present communication in silico mining of microbial
      genomes has been carried out to find novel sources of nitrilases. The sequences
      selected were analyzed for homology and considered for designing motifs. The
      manually designed motifs based on amino acid sequences of nitrilases were used to
      screen 2000 microbial genomes (translated to proteomes). This resulted in
      identification of one hundred thirty-eight putative/hypothetical sequences which
      could potentially code for nitrilase activity. In vitro validation of nine
      predicted sources of nitrilases was done for nitrile/cyanide hydrolyzing
      activity. Out of nine predicted nitrilases, Gluconacetobacter diazotrophicus,
      Sphingopyxis alaskensis, Saccharomonospora viridis, and Shimwellia blattae were
      specific for aliphatic nitriles, whereas nitrilases from Geodermatophilus
      obscurus, Nocardiopsis dassonvillei, Runella slithyformis, and Streptomyces albus
      possessed activity for aromatic nitriles. Flavobacterium indicum was specific
      towards potassium cyanide (KCN) which revealed the presence of nitrilase homolog,
      that is, cyanide dihydratase with no activity for either aliphatic, aromatic, or
      aryl nitriles. The present study reports the novel sources of nitrilases and
      cyanide dihydratase which were not reported hitherto by in silico or in vitro
      studies.

PMID- 28497060
TI  - Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta
      Analysis of Randomized Controlled Trials.
AB  - Background. Whether additional benefit can be achieved with the use of L
      carnitine (L-C) in patients with chronic heart failure (CHF) remains
      controversial. We therefore performed a meta-analysis of randomized controlled
      trials (RCTs) to evaluate the effects of L-C treatment in CHF patients. Methods.
      Pubmed, Ovid Embase, Web of Science, and Cochrane Library databases, Chinese
      National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese
      Biomedical (CBM) database, and Chinese Science and Technology Periodicals
      database (VIP) until September 30, 2016, were identified. Studies that met the
      inclusion criteria were systematically evaluated by two reviewers independently.
      Results. 17 RCTs with 1625 CHF patients were included in this analysis. L-C
      treatment in CHF was associated with considerable improvement in overall efficacy
      (OR = 3.47, P < 0.01), left ventricular ejection fraction (LVEF) (WMD: 4.14%, P =
      0.01), strike volume (SV) (WMD: 8.21 ml, P = 0.01), cardiac output (CO) (WMD:
      0.88 L/min, P < 0.01), and E/A (WMD: 0.23, P < 0.01). Moreover, treatment with L
      C also resulted in significant decrease in serum levels of BNP (WMD: -124.60
      pg/ml, P = 0.01), serum levels of NT-proBNP (WMD: -510.36 pg/ml, P < 0.01), LVESD
      (WMD: -4.06 mm, P < 0.01), LVEDD (WMD: -4.79 mm, P < 0.01), and LVESV (WMD: 
      20.16 ml, 95% CI: -35.65 to -4.67, P < 0.01). However, there were no significant
      differences in all-cause mortality, 6-minute walk, and adverse events between L-C
      and control groups. Conclusions. L-C treatment is effective for CHF patients in
      improving clinical symptoms and cardiac functions, decreasing serum levels of BNP
      and NT-proBNP. And it has a good tolerance.

PMID- 28497062
TI  - A Clinical Retrospective Study of Distal Extension Removable Partial Denture with
      Implant Surveyed Bridge or Stud Type Attachment.
AB  - This study was performed to make comparative analysis of the clinical findings
      between the two different types of the implant-assisted removable partial
      dentures: removable partial dentures using implant surveyed bridge as an abutment
      (ISBRPD) and overdenture type of removable partial denture using implant
      attachment (IARPD). Implant cumulative survival rate, marginal bone resorption,
      probing depth, peri-implant inflammation, bleeding, plaque, calculus, and
      complications were evaluated on 24 patients who were treated with implants in
      conjunction with removable partial denture and have used them for at least 1 year
      (ISCRPD: n = 12; IARPD: n = 12). There was no failed implant and all implants
      were functioning without clinical mobility. Marginal bone loss of ISCRPD (1.44 +/
      0.57 mm) was significantly lower than that of IARPD (p < 0.05). There was no
      significant difference in probing depth, peri-implant inflammation, bleeding, and
      plaque between the two groups (p > 0.05), while the calculus was significantly
      more observed in ISCRPD group than in IARPD group (p < 0.05). The retention loss
      of IARPD was the most common complication. Within the limits of the present
      study, it was found that well-planned ISBRPD was clinically appropriate.
      Longitudinal and systematic clinical studies are necessary to confirm these
      results.

PMID- 28497063
TI  - Level of Knowledge and Practice of Mothers on Minimum Dietary Diversity Practices
      and Associated Factors for 6-23-Month-Old Children in Adea Woreda, Oromia,
      Ethiopia.
AB  - Background. Globally, undernutrition is responsible for at least 35% of deaths in
      children less than 5 years of age and estimated 6% of under-five deaths can be
      prevented by ensuring optimal complementary feeding especially the dietary
      diversity and meal frequency. In Ethiopia, 5% of children were fed according to
      minimum standards with respect to food diversity. Objective. To assess the level
      of knowledge and practice of mothers on dietary diversity practices and
      associated factors for children 6-23 months in Adea woreda. Methods. Community
      based cross-sectional study was conducted. A sample of 730 mothers who have
      children in the age group of 6-23 months were selected using systematic sampling.
      Logistic regression model was fitted in order to identify factors associated with
      knowledge and practice of dietary diversity practice. Result. Of the total 700,
      357 (51%) were knowledgeable on dietary diversity but 112 (16%) practiced
      appropriate dietary diversity practice for their 6-23-month-old children.
      Husbands' education (AOR = 2.79, 95% CI = (1.55, 5.00)), mothers' age, and
      marital status were significantly associated with knowledge of mothers. Mothers'
      age, husbands' education, marital status, and knowledge of mothers were
      significantly associated with mothers' dietary diversity for 6-23-month-old
      children. Conclusion. This study showed that approximately half of the mothers
      have good knowledge on minimum dietary diversity for children 6-23 months old and
      very low proportion of children 6-23 months old received diversified meal
      according to Infant and Young Child Feeding indicators. It was identified that
      different factors are responsible for this discrepancy.

PMID- 28497064
TI  - The Effect of Surgical Intervention for Delayed Cervical Central Cord Syndrome.
AB  - The authors retrospectively studied 11 patients with delayed cervical central
      cord syndrome (CCS) to investigate the efficacy of the surgical intervention on
      treatment for delayed CCS. The American Spinal Injury Association (ASIA) motor
      scores, Japanese Orthopedic Association (JOA) scores, SF-36 scores, and
      neurologic status were analyzed preoperatively and at each time point of
      postoperative follow-up. The results show that patients with reversible spinal
      cord injury caused by delayed central cord syndrome can recover significantly
      after surgical intervention. Therefore, we suggest that surgical intervention is
      still the ideal choice for delayed cervical central cord syndrome.

PMID- 28497065
TI  - A Low Psoas Muscle Index before Treatment Can Predict a Poorer Prognosis in
      Advanced Bladder Cancer Patients Who Receive Gemcitabine and Nedaplatin Therapy.
AB  - Introduction. Gemcitabine and cisplatin (GC) is a gold-standard first-line
      systemic chemotherapy for advanced urothelial carcinoma (UC). However, it may
      cause severe adverse effects such as renal toxicity, gastrointestinal toxicity,
      and neurotoxicity. Sarcopenia is the age-related loss of skeletal muscle mass. A
      correlation between sarcopenia and the oncological prognosis has been reported.
      In UC, several studies have noted that patients with sarcopenia had a greater
      incidence of complications and worse survival after radical cystectomy or
      chemotherapy. Our institute introduced gemcitabine and nedaplatin (GN) for UC
      patients with renal failure. We investigated whether the presence of sarcopenia
      predicted the prognosis of patients with advanced UC who were treated by GN
      chemotherapy. Methods. A total of 27 patients (male, n = 21; female, n = 6)
      received GN therapy for metastatic UC from 2005 to 2016. The institutional review
      board of Yokohama City University Hospital approved this study. The psoas muscle
      index (PMI, cm2/m2) was calculated using this formula: right psoas muscle area
      (cm2)/the square of the body height (m2). The overall survival (OS) of the high
      PMI group (male: >=2.49, female: >=2.07) and low PMI group (male: <2.49, female:
      <2.07) was compared. Results. Kaplan-Meier survival curves and a log-rank test
      revealed that the high PMI group had significantly better OS than the low PMI
      group (p = 0.015). The mean survival of the high and low PMI groups was 561 days
      and 223 days, respectively. Conclusions. In the present study, we revealed that
      sarcopenia (a low psoas muscle volume) might be a predictive factor for poorer
      overall survival in patients with advanced urothelial carcinoma who are
      undergoing GN chemotherapy.

PMID- 28497066
TI  - Morphometric Analysis of the Clavicles in Chinese Population.
AB  - The clavicle has a complex geometry that makes plate fixation technically
      difficult. The current study aims to measure the anatomical parameters of Chinese
      clavicles as reference for plate design. One hundred clavicles were analyzed. The
      clavicle bone model was reconstructed by using computed tomography images. The
      length, diameters, and curvatures of the clavicle were then measured. The female
      clavicle was shorter, more slender, and less curved in lateral part than the male
      clavicle. There was a positive relationship between height and clavicle
      parameters except lateral curve and depth. The measurements of Chinese clavicles
      were generally smaller than Caucasians. The clavicle curves were correlated with
      the bone length; thus consideration of the curve variations may be necessary as
      designing size distribution of clavicle plate.

PMID- 28497067
TI  - The Influence of Tribological Pairings and Other Factors on Migration Patterns of
      Short Stems in Total Hip Arthroplasty.
AB  - Over the last decade, the number of short stem total hip arthroplasty procedures
      has increased. Along with the possible benefits associated with short stems is a
      smaller implant-bone contact surface, which may have a negative influence on
      primary stability and impair osseointegration. Previous studies observed
      migration of short stems, especially within the first three months. The variables
      that influence migration in short stem hip implants remain unknown. Therefore,
      the purpose of this study was to associate the migration of short stems with its
      possible influencing variables. Migration data from two different short stem
      studies were retrospectively analyzed. Migration within the first two
      postoperative years was determined by model-based Roentgen stereophotogrammetric
      analysis. Migration was correlated to bearing couple, type and size of stem, size
      of acetabular cup, and age, gender, weight, and height of patients using a
      multiple factor analysis. Eigenvalue analysis explained 80.7% of the overall
      variance for the first three dimensions. The four most dominant variables in the
      first dimension were weight, stem size, acetabular cup size, and patient height
      (correlations of 0.81, 0.80, 0.71, and 0.70, resp.). None of the analyzed
      parameters (bearing couple, type and size of stem, size of acetabular cup, and
      age, gender, weight, and height of patients) affected the migration pattern of
      short stem THA with primary metaphyseal fixation.

PMID- 28497068
TI  - Effects of Force Load, Muscle Fatigue, and Magnetic Stimulation on Surface
      Electromyography during Side Arm Lateral Raise Task: A Preliminary Study with
      Healthy Subjects.
AB  - The aim of this study was to quantitatively investigate the effects of force
      load, muscle fatigue, and extremely low-frequency (ELF) magnetic stimulation on
      surface electromyography (SEMG) signal features during side arm lateral raise
      task. SEMG signals were recorded from 18 healthy subjects on the anterior deltoid
      using a BIOSEMI ActiveTwo system during side lateral raise task (with the right
      arm 90 degrees away from the body) with three different loads on the forearm (0
      kg, 1 kg, and 3 kg; their order was randomized between subjects). The arm
      maintained the loads until the subject felt exhausted. The first 10 s recording
      for each load was regarded as nonfatigue status and the last 10 s before the
      subject was exhausted was regarded as fatigue status. The subject was then given
      a five-minute resting between different loads. Two days later, the same
      experiment was repeated on every subject, and this time the ELF magnetic
      stimulation was applied to the subject's deltoid muscle during the five-minute
      rest period. Three commonly used SEMG features, root mean square (RMS), median
      frequency (MDF), and sample entropy (SampEn), were analyzed and compared between
      different loads, nonfatigue/fatigue status, and ELF stimulation and no
      stimulation. Variance analysis results showed that the effect of force load on
      RMS was significant (p < 0.001) but not for MDF and SampEn (both p > 0.05). In
      comparison with nonfatigue status, for all the different force loads with and
      without ELF stimulation, RMS was significantly larger at fatigue (all p < 0.001)
      and MDF and SampEn were significantly smaller (all p < 0.001).

PMID- 28497069
TI  - Characterization of Focal Liver Lesions Indistinctive on B Mode Ultrasound:
      Benefits of Contrast-Enhanced Ultrasound.
AB  - Aim. The aim of this prospective study was to evaluate the additional value of
      contrast-enhanced ultrasound (CEUS) in identifying and characterizing of focal
      liver lesions (FLLs) that are indistinctive on B mode ultrasound (BMUS). Methods.
      The study focused on 70 consecutive patients (male 46, female 24; mean age, 53.1
      years +/- 10). All lesions were detected by MRI but could not be clearly
      visualized by BMUS. CEUS was performed by injected SonoVue(r) (Bracco Imaging
      Spa, Milan, Italy) as a quick bolus into the antecubital vein. All lesions were
      proved by pathologic and MRI findings as primary or metastatic hepatic
      malignancies. Results. On CEUS, 45 (64.2%) FLLs displayed arterial
      hyperenhancement and 55 (78.5%) lesions showed hypoenhancement in portal venous
      and late phase (PVLP). Homogeneous and complete hyperenhancement pattern during
      the arterial phase is highly suspicious for HCC in liver cirrhosis (96.8%).
      Arterial isoenhancement and early washout during PVLP are characteristic for
      metastasis (73.3%). For recurrence lesions, arterial hyperenhancement and
      isoenhancement during PVLP are more common (60%). Conclusion. CEUS may provide
      added diagnostic values in FLLs appearing indistinctive on BMUS. Presence of
      early arterial enhancement and washout during PVLP may be helpful for detection
      of those lesions.

PMID- 28497071
TI  - Advances in Research with LGBTQ Youth in Schools.

PMID- 28497070
TI  - Impact of polyethylene glycol 400/propylene glycol/hydroxypropyl-guar and 0.1%
      sodium hyaluronate on postoperative discomfort following cataract extraction
      surgery: a comparative study.
AB  - BACKGROUND: Universal postoperative guidelines for cataract extraction surgery
      are yet to be introduced. Artificial tears are gaining popularity as an
      additional integral component of the postoperative regime. The primary objective
      of this study was to explore the impact of two prevalent artificial tear
      preparations on postoperative discomfort following cataract extraction surgery.
      METHODS: A total of 180 patients that underwent cataract extraction surgery were
      randomly divided into three groups according to their postoperative regime: a)
      Study group 1 (SG1) received a fixed combination of tobramycin and dexamethasone
      (FCTD) quid for 3 weeks and, additionally polyethylene glycol 400/propylene
      glycol/hydroxypropyl-guar quid, for 6 weeks, b) Study group 2 (SG2) received FCTD
      quid for 3 weeks and, additionally 0.1% sodium hyaluronate provided in the
      COMOD(r) device quid, for 6 weeks, and, c) Control Group (CG) received only FCTD
      quid for 3 weeks. The following indexes were evaluated at three postoperative
      checkpoints: 1) Subjective discomfort index (SDI) derived from four direct 10
      scale Likert-type questions that were addressed to the patient and pertained to:
      a) foreign body sensation (FBS), b) blinking discomfort (BD), c) stinging
      sensation (SS), d) tearing sensation (TS), 2) Tear break-up time (TBUT), 3)
      Central corneal thickness (CCT) and, 4) Central Corneal Sensitivity (CCS).
      RESULTS: Both groups showed increased CCT values at the first examination point
      and reduced CCS values at all examination points. Furthermore, both SGs had
      better TBUT times at all examination points compared to CG (CG: 8.86 +/- 1.08,
      SG1: 9.59 +/- 1.45, CG2: 9.45 +/- 1.33, p < 0.05). BD was significantly better in
      both SGs only at the 1st week of examination, while SDI values were better until
      the 3rd week and only borderline better at 6th week. Lastly, no significant
      differences were detected between SGs, regarding all parameters, at all
      examination points. CONCLUSION: Polyethylene glycol 400/propylene
      glycol/hydroxypropyl-guar and 0.1% sodium hyaluronate provided in the COMOD(r)
      device seem to be equally efficient in alleviating OSD symptoms following
      cataract extraction surgery and any of them should be routinely added to the
      postoperative regime. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      https://clinicaltrials.gov/ct2/show/NCT02558218NCT02558218.

PMID- 28497072
TI  - Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without
      Apparent Toxicity after Intracisternal Delivery.
AB  - Intravenous administration of adeno-associated virus serotype 9 (AAV9)/hMECP2 has
      been shown to extend the lifespan of Mecp2-/y mice, but this delivery route
      induces liver toxicity in wild-type (WT) mice. To reduce peripheral transgene
      expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the
      cisterna magna (ICM). AAV9/hMECP2 (1 * 1012 viral genomes [vg]; ICM) extended
      Mecp2-/y survival but aggravated hindlimb clasping and abnormal gait phenotypes.
      In WT mice, 1 * 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A
      lower dose mitigated these adverse phenotypes but failed to extend survival of
      Mecp2-/y mice. Thus, ICM delivery of this vector is impractical as a treatment
      for Rett syndrome (RTT). To improve the safety of MeCP2 gene therapy, the gene
      expression cassette was modified to include more endogenous regulatory elements
      believed to modulate MeCP2 expression in vivo. In Mecp2-/y mice, ICM injection of
      the modified vector extended lifespan and was well tolerated by the liver but did
      not rescue RTT behavioral phenotypes. In WT mice, these same doses of the
      modified vector had no adverse effects on survival or neurological phenotypes. In
      summary, we identified limitations of the original vector and demonstrated that
      an improved vector design extends Mecp2-/y survival, without apparent toxicity.

PMID- 28497073
TI  - Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly
      Efficient CRISPR/Cas9-Mediated Gene Editing.
AB  - The CRISPR/Cas9 systems have revolutionized the field of genome editing by
      providing unprecedented control over gene sequences and gene expression in many
      species, including humans. Lentiviral vectors (LVs) are one of the primary
      delivery platforms for the CRISPR/Cas9 system due to their ability to accommodate
      large DNA payloads and sustain robust expression in a wide range of dividing and
      non-dividing cells. However, long-term expression of LV-delivered Cas9/guide RNA
      may lead to undesirable off-target effects characterized by non-specific RNA-DNA
      interactions and off-target DNA cleavages. Integrase-deficient lentiviral vectors
      (IDLVs) present an attractive means for delivery of CRISPR/Cas9 components
      because: (1) they are capable of transducing a broad range of cells and tissues,
      (2) have superior packaging capacity compared to other vectors (e.g., adeno
      associated viral vectors), and (3) they are expressed transiently and demonstrate
      very weak integration capability. In this manuscript, we aimed to establish IDLVs
      as a means for safe and efficient delivery of CRISPR/Cas9. To this end, we
      developed an all-in-one vector cassette with increased production efficacy and
      demonstrated that CRISPR/Cas9 delivered by the improved IDLV vectors can mediate
      rapid and robust gene editing in human embryonic kidney (HEK293T) cells and post
      mitotic brain neurons in vivo, via transient expression and with higher gene
      targeting specificity than the corresponding integrase-competent vectors.

PMID- 28497074
TI  - Efficient Production of Papillomavirus Gene Delivery Vectors in Defined In Vitro
      Reactions.
AB  - Papillomavirus capsids can package a wide variety of nonviral DNA plasmids and
      deliver the packaged genetic material to cells, making them attractive candidates
      for targeted gene delivery vehicles. However, the papillomavirus vectors
      generated by current methods are unlikely to be suitable for clinical
      applications. We have developed a chemically defined, cell-free, papillomavirus
      based vector production system that allows the incorporation of purified plasmid
      DNA (pseudogenome) into high-titer papillomavirus L1/L2 capsids. We investigated
      the incorporation of several DNA forms into a variety of different papillomavirus
      types, including human and animal types. Our results show that papillomavirus
      capsids can package and transduce linear or circular DNA under defined
      conditions. Packaging and transduction efficiencies were surprisingly variable
      across capsid types, DNA forms, and assembly reaction conditions. The
      pseudoviruses produced by these methods are sensitive to the same entry
      inhibitors as cell-derived pseudovirions, including neutralizing antibodies and
      heparin. The papillomavirus vector production systems developed in this study
      generated as high as 1011 infectious units/mg of L1. The pseudoviruses were
      infectious both in vitro and in vivo and should be compatible with good
      manufacturing practice (GMP) requirements.

PMID- 28497075
TI  - Development of a Novel AAV Gene Therapy Cassette with Improved Safety Features
      and Efficacy in a Mouse Model of Rett Syndrome.
AB  - Rett syndrome (RTT), caused by loss-of-function mutations in the MECP2 gene, is a
      neurological disorder characterized by severe impairment of motor and cognitive
      functions. The aim of this study was to investigate the impact of vector design,
      dosage, and delivery route on the efficacy and safety of gene augmentation
      therapy in mouse models of RTT. Our results show that AAV-mediated delivery of
      MECP2 to Mecp2 null mice by systemic administration, and utilizing a minimal
      endogenous promoter, was associated with a narrow therapeutic window and resulted
      in liver toxicity at higher doses. Lower doses of this vector significantly
      extended the survival of mice lacking MeCP2 or expressing a mutant T158M allele
      but had no impact on RTT-like neurological phenotypes. Modifying vector design by
      incorporating an extended Mecp2 promoter and additional regulatory 3' UTR
      elements significantly reduced hepatic toxicity after systemic administration.
      Moreover, direct cerebroventricular injection of this vector into neonatal Mecp2
      null mice resulted in high brain transduction efficiency, increased survival and
      body weight, and an amelioration of RTT-like phenotypes. Our results show that
      controlling levels of MeCP2 expression in the liver is achievable through
      modification of the expression cassette. However, it also highlights the
      importance of achieving high brain transduction to impact the RTT-like
      phenotypes.

PMID- 28497076
TI  - Molecular Mechanism of beta-Catenin Signaling Pathway Inactivation in ETV1
      Positive Prostate Cancers.
AB  - In the United States of America, prostate cancer is the second most common age
      related cancer among men. African-American men have the highest incidence of, and
      mortality rate from this disease in the United States. According to the American
      Cancer Society, 29% of all cancer cases and 9% of all cancer deaths are a result
      of prostate cancer. Individuals who are at highest risk include African-American
      men, men over 60 years of age, and those with a family history of the disease.
      African-Americans also have twice the risk of developing prostate cancer as
      compared to Caucasians. Erythroblastosis virus E26 transformation-specific (ETS)
      factors play an important role in human cancers. ETS Variant 1 (ETV1), an ETS
      factor, is notable for its association in prostate cancers, where truncated ETV1
      (dETV1) or its full length counterpart is overexpressed in approximately 10% of
      the prostate cancer patients. Prostate cancer tumorigenesis may be initiated by
      deregulation of the Wnt/beta-catenin pathway. Mutations that stabilize beta
      catenin were shown to contribute to the loss of cell-growth control in
      tumorigenesis. We hypothesized that ETV1's interaction with components of the
      Wnt/beta-catenin pathway may alter beta-catenin's interaction with downstream
      tumor-suppressor genes, which are critical in regulating apoptosis and cell
      growth properties of prostate cells. Our results demonstrate for the first time
      that ETV1 alters beta-catenin activity by activating kinases that regulate
      Wnt/beta-catenin activity through post-translational modification in prostate
      cancer cells. We further demonstrate that therapeutic agents such as PD98059,
      that reverse effect of ETV1 on Wnt/beta-catenin signaling pathway, can be used to
      target ETV1-positive prostate cancer cells. These therapeutic agents could have a
      profound impact on prevention and treatment of prostate cancer which may help to
      reduce health disparity seen in minority patients. Understanding the role of ETV1
      in Wnt/beta-catenin pathway will also allow us to develop better diagnostic
      tools, which can be used as a biomarker for ETV1-positive prostate cancers.

PMID- 28497078
TI  - Joubert syndrome; misleading presentation of two cases as pseudo-tumor cerebri
      and literature review.
AB  - Joubert syndrome is a rare autosomal recessive disorder that may have different
      clinical presentation such as ataxia, hyperpnea, sleep apnea, nystagmus,
      hypotonia, seizure and retinitis pigmentosa. We present a 22-year-old girl and
      her older sibling, labeled as cerebral palsy. She had renal transplant years ago
      without the true diagnosis of the disorder. Brain imaging revealed the classic
      "molar tooth sign" appearance, and clinical evaluation established the diagnosis
      for both of the siblings. Imaging should be done to evaluate the
      neuroradiological findings of Joubert syndrome. With a neonate with Joubert
      syndrome in a family, antenatal diagnosis by ultrasound is crucial for future
      siblings.

PMID- 28497077
TI  - What do we know about pediatric renal microlithiasis?
AB  - Renal or calyceal microlithiasis is a common disorder with increasing prevalence
      especially in infants and younger children. The main presenting symptoms and the
      underlying metabolic abnormalities of renal microlithiasis are similar to renal
      stone. Although renal microlithiasis is considered as a main problem of the
      health system with diverse etiologies, our information about its natural course
      is very limited. Hence, further investigations to make an appropriate clinical
      approach to this entity is mandatory. Also, general practitioners, pediatricians,
      nephrologists and urologists have to be well educated regarding renal
      microlithiasis for early diagnosis, appropriate evaluation and proper management
      of this entity. In this review study, we focused on collection of the present
      information about different aspects of renal microlithiasis in children.

PMID- 28497079
TI  - Spontaneous rupture of continent cutaneous urinary diversion after 25 years.
AB  - Spontaneous rupture of a continent cutaneous urinary diversion is uncommon and
      diagnosis of this situation requires a high degree of suspicion. In this paper we
      present a 66-year-old man with continent cutaneous pouch after radical
      cystoprostatectomy that presented with spontaneous perforation 25 years after
      surgery. Spontaneous pouch perforation in our case after 25 years emphasizes the
      need for long follow-up in patients with continent diversion.

PMID- 28497080
TI  - Applying data mining techniques to determine important parameters in chronic
      kidney disease and the relations of these parameters to each other.
AB  - Introduction: Chronic kidney disease (CKD) includes a wide range of
      pathophysiological processes which will be observed along with abnormal function
      of kidneys and progressive decrease in glomerular filtration rate (GFR).
      According to the definition decreasing GFR must have been present for at least
      three months. CKD will eventually result in end-stage kidney disease. In this
      process different factors play role and finding the relations between effective
      parameters in this regard can help to prevent or slow progression of this
      disease. There are always a lot of data being collected from the patients'
      medical records. This huge array of data can be considered a valuable source for
      analyzing, exploring and discovering information. Objectives: Using the data
      mining techniques, the present study tries to specify the effective parameters
      and also aims to determine their relations with each other in Iranian patients
      with CKD. Material and Methods: The study population includes 31996 patients with
      CKD. First, all of the data is registered in the database. Then data mining tools
      were used to find the hidden rules and relationships between parameters in
      collected data. Results: After data cleaning based on CRISP-DM (Cross Industry
      Standard Process for Data Mining) methodology and running mining algorithms on
      the data in the database the relationships between the effective parameters was
      specified. Conclusion: This study was done using the data mining method
      pertaining to the effective factors on patients with CKD.

PMID- 28497081
TI  - Relationship between serum irisin, glycemic indices, and renal function in type 2
      diabetic patients.
AB  - Introduction: Irisin is a novel peptide that plays notable role in human and
      animal biology and physiology. It has been reported that irisin may improve
      insulin resistance and related disturbances. Objectives: The aim of this
      investigation was to assess the relationship between serum irisin, glycemic
      indices, and renal function in diabetic subjects. Patients and Methods: In this
      cross-sectional study, a total of 102 type 2 diabetes mellitus (T2DM) patients
      were recruited. Blood biochemical parameters, including fasting plasma sugar
      (FBS), glycosylated hemoglobin (HbA1C), serum uric acid (sUA), creatinine
      concentration and glomerular filtration rate (GFR) were measured. All statistical
      analysis was performed with SPSS 16.0. Results: There was a positive correlation
      between irisin and age (P=0.05, r=0.19) and a negative correlation between irisin
      and body mass index (BMI) (P=0.01, r=-0.25) was detected. There was a significant
      difference of serum irisin level between patients with normal and abnormal FBS
      too. Conclusion: In this study we found, irisin concentration was increased with
      age, decreased with BMI, and it was higher in subject with abnormal FBS. Thus
      further research is needed to provide inclusive understanding of irisin
      associated physiological effects and possible implications in clinical
      conditions.

PMID- 28497082
TI  - Evaluation of selenium on kidney function following ischemic injury in rats;
      protective effects and antioxidant activity.
AB  - Introduction: Renal dysfunction is caused by ischemia-reperfusion (I/R) injury,
      which is a common problem in kidney surgery or kidney transplantation. The human
      body consists of enormous complex antioxidant systems, which inquires adequate
      selenium (Se) absorption for normal physiologic function. It is known that Se has
      some antioxidant effects. Objectives: In the present research, effects of the Se
      on damages caused by I/R injury investigated. Materials and Methods: In this
      experimental research, four groups of rats (weighing 220+/-10 g) used, include
      control group, I/R group, healthy group treated with Se for two weeks, and I/R
      group with two-week Se treatment. On the test day, I/R was treated in both right
      and left renal arteries for 45 minutes and the reperfusion was done for 24 hours.
      Results: In I/R group, the amount of urea and serum creatinine (Cr) was an injury
      indicator of the kidney cells which showed a significant increase compared with
      the control group. When the treatment with Se significantly reduced these
      indicators, glutathione (GSH) enzyme levels reduced significantly in the second
      group and the enzyme levels increased due to Se treatment in the fourth group.
      Furthermore, malondialdehyde (MDA) enzyme levels increased in I/R group due to
      the Se treatment in the fourth group which was significantly reduced. In
      addition, the tissue damage was reduced in the fourth group compared with I/R
      group. Conclusion: Se has a protective effect against the I/R injury. This effect
      might be due to the antioxidant properties of Se.

PMID- 28497083
TI  - Impact of FGF23 level on calcium and phosphorus levels in post-renal
      transplantation.
AB  - Introduction: The level of fibroblast growth factor 23 (FGF23) may be considered
      as a prognostic factor for assessing renal function in regulating components of
      phosphate and vitamin D hemostasis. Objectives: The present study aimed to
      evaluate the prognostic value of FGF23 level to predict renal function after
      renal transplantation. Patients and Methods: Fifteen consecutive patients
      scheduled for renal transplantation. To assess renal function status, the MDRD
      formula and isotope scan were applied. The study endpoint was to assess the level
      of FGF23 and other factors involving calcium and phosphorus metabolism before and
      also 3 and 12 months after transplantation and also to determine role of FGF23 to
      predict postoperative renal function. Results: The mean level of FGF23 was
      839.51+/-694.56 rhog/mL at baseline that reduced to 44.31+/-22.01 rhog/mL and
      20.13+/-36.50 rhog/mL, 3 and 12 months after initial assessment. The levels of
      FGF23 was significantly lower at 3 and 12 months after baseline (P=0.01 and
      P=0.02, respectively) with no difference in FGF23 level between the time points
      of 3 and 12 months after transplantation. Baseline level of FGF23 was found to be
      higher in the patients with higher glomerular filtration rate (GFR), in older
      patients, in males, in those patients with diabetic nephropathy, in those with
      acceptable renal function than in patients who suffered transplant rejection.
      Conclusion: The level of postoperative FGF23 is an important marker for secretion
      of phosphorus from kidneys emphasizing the central role of FGF23 marker to
      regulate calcium and phosphorus metabolism after a successful renal
      transplantation.

PMID- 28497084
TI  - Effects of radiofrequency radiation in the presence of gold nanoparticles for the
      treatment of renal cell carcinoma.
AB  - Introduction: The most common type of kidney cancer is renal cell carcinoma
      (RCC), which accounts for more than 80% of all kidney cancers. Objectives: The
      aim of this study was to evaluate the effects of radiofrequency (RF) radiation in
      the presence of gold nanoparticles (GNPs) for the treatment of RCC. Materials and
      Methods: Human embryonic kidney (HEK) cancer cells were divided into 6 groups.
      Various tests were performed on HEK cells in the presence of RF and GNPs. In
      order to investigate the radiation effects on the cells' survival, MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-iphenyltetrazolium bromide] assay was performed at
      different days during and post-irradiation period. The repeated measure analysis
      of variance (ANOVA) method was used for statistical analysis of the cells'
      survival using SPSS version 16.0. A significant level of 0.05 was considered to
      the tests. Results: Using the ANOVA test, a significant decrease in cell's
      survival was seen in the RF exposed group 3 compared to the control group
      (P=0.035). While, differences were not significant between RF exposed group 2 and
      the control group (P>0.05). A significant decrease in cell's survival in the RF
      exposed groups 5 (P=0.025) and 6 (P=0.018) at the presence of GNP compared to the
      control group was seen. Conclusion: Results of this study showed that, this
      method can be efficiently used for RCC treatment as an alternative to
      nephrectomy. More follow up in vivo studies on mammalians are needed to
      investigate the potential of the presented method for clinical applications.

PMID- 28497085
TI  - Evaluation of water and electrolytes disorders in severe acute diarrhea patients
      treated by WHO protocol in eight large hospitals in Tehran; a nephrology
      viewpoint.
AB  - Introduction: The most common cause of death from diarrhea is the shock caused by
      dehydration, electrolytes and acid-base disorders. Objectives: The aim of this
      study was to evaluate water and electrolytes disorders in diarrhea patients after
      treating severe acute diarrhea. Patients and Methods: In this study we used a
      historical cohort and studied patients who were hospitalized due to acute
      diarrhea and were similarly treated for dehydration and water and electrolyte
      disorders as recommended by the World Health Organization (WHO) guideline.
      Electrolytes, pH, serum creatinine (Cr) level on admission and during treatment
      were recorded. Patients with underlying diseases were excluded from the study.
      Results: Of 121 patients who were enrolled in the study, 67.8% had hyponatremia
      on admission (plasma Na <137 mEq/L) and 5.8% had hypernatremia. Around, 33.88% of
      patients had hypokalemia and 2.4% had hyperkalemia. All hyperkalemia disorders
      were treated, but 87.1% of patients had hypokalemia or low potassium levels, or
      they were affected by uncorrected hypokalemia and were in need of further
      measures. Of all, 56.75% had acidosis and 21% of patients with acidosis were not
      treated or the severity of their acidosis increased during treatment. There was a
      significant relationship between acute renal failure (ARF) and hypokalemia at the
      time of admission (P<0.001), potassium loss during treatment (P<0.001), acidosis
      (0.005), and cholera-related diarrhea (0.05). Conclusion: The high prevalence of
      hypokalemia in these patients as well as potassium loss during treatment
      indicates insufficient level of potassium in the therapeutic solutions. Mild
      hyponatremia in most patients highlights the need for isotonic solutions to treat
      dehydration.

PMID- 28497086
TI  - The effect of vibration on the severity of restless legs syndrome in hemodialysis
      patients.
AB  - Introduction: The restless legs syndrome (RLS) is a neurological disorder in
      patients undergoing hemodialysis. This syndrome causes individual's disturbed
      rest, discomfort, and stress, and secondarily to weakened functioning and
      disturbance in occupational activities and familial life. Objectives: The present
      study aimed at investigate the effect of vibration on the severity of the
      manifestation of symptoms of RLS in hemodialysis patients. Patients and Methods:
      This is an interventional before-after study conducted on 80 patients with RLS in
      hemodialysis wards of Yazd hospitals. The samples were selected randomly and
      intervention was performed on the patients as vibration for 10 minutes three
      times per week during 4 succeeding weeks. The questionnaire of severity of RLS
      was completed before the study and at the last day of intervention before and
      after vibration. The data were analyzed with SPSS 23 using descriptive statistics
      and paired t test (P<0.05). Results: Our findings showed that most patients were
      at the moderate level of severity of symptoms before (68.8%) and after (78.8%)
      intervention and there was a significant difference in the mean score of RLS
      between before (18.99) and after (12.82) intervention (P=0.001). Conclusion:
      Based on the results of this study, it can be concluded that vibration decreases
      the severity of symptoms of RLS in hemodialysis patients. Hence, it is
      recommended that vibration be used as a cost-effective and safe procedure to
      improve the symptoms of RLS in this group of patients.

PMID- 28497087
TI  - Renal function in patients with diabetic foot infection; does antibiotherapy
      affect it?
AB  - Introduction: Antibiotic treatment (antibiotherapy) of diabetic foot ulcers has
      been proven to have toxic effect on renal function. Objectives: This study aimed
      to evaluate renal function in patients with diabetic foot infection. Patients and
      Methods: This cross-sectional retrospective study was performed on 142 patients
      with diabetic foot ulcers hospitalized in Shahid Yahyanejad hospital of Babol
      during 2013. After referring to profile of the patients, they were assigned to
      participate in two groups: group A consisted of patients receiving antibiotics
      with a low risk renal toxicity and patients who received antibiotics with a
      higher risk of renal toxicity were placed in group B. Glomerular filtration rate
      (GFR) was measured and calculated based on serum concentration of creatinine and
      Cockcroft-Gault equation. Data was analyzed using SPSS version 20.0 with chi
      square, t test and paired t tests. Results: Group A consisted of 74 patients
      (52.1%) and 68 patients (47.9%) participated in group B. GFRs before and after
      antibiotherapy were 64.73+/-33.87 cc/min and 59.10+/-30.51 cc/min, respectively
      (P=0.004). In group B, GFR decreased significantly after antibiotherapy
      (P=0.002). Conclusion: According to the present study, renal function decreased
      after antibiotherapy and in patients who received antibiotics with higher
      nephrotoxicity rate, the rate of this decline was higher.

PMID- 28497088
TI  - Pulmonary hypertension among patients undergoing hemodialysis.
AB  - Introduction: The epidemiology of pulmonary hypertension (PHT) among long-term
      hemodialysis patients has been described in relatively small studies in Iran.
      Objectives: The purpose of this study was to evaluate the prevalence of PHT and
      its relationship among end-stage renal disease (ESRD) patients undergoing long
      term hemodialysis (HD). Patients and Methods: In a cross-sectional study,
      patients with ESRD treated with HD for at least 3 months in the Imam hospital
      enrolled for the study. PHT was defined as an estimated systolic pulmonary artery
      pressure (PAP) equal to or higher than 25 mm Hg using echocardiograms performed
      by cardiologist. Results: A total of 69 HD patients were included in the
      investigation. The mean of age of our patients was 52.6+/-15.3 years. The mean
      duration of HD was 39+/-36 months. The mean ejection fraction was 45+/-7%. The
      prevalence of PHT was 62.3%. These patients were more likely to have lower
      ejection fraction. The PHT was more common among female HD patients. We did not
      find any association between PHT and cause of ESRD, duration of HD, anemia and
      serum calcium, phosphor and parathyroid hormone levels. Conclusion: Our findings
      show that PHT is a common problem among ESRD patients undergoing maintenance HD
      and it is strongly associated with heart failure. It is necessary to screen this
      disorder among these patients.

PMID- 28497089
TI  - Impact of oral capsule of Peganum harmala on alleviating urinary symptoms in men
      with benign prostatic hyperplasia; a randomized clinical trial.
AB  - Introduction: Benign prostatic hyperplasia (BPH) is considered as a major cause
      of lower urinary tract symptoms (LUTS) in older men and its most common sign is
      nocturia. Objectives: This study aimed to determine the effect of the seeds of
      Peganum harmala compared with tamsulosin on alleviating urinary symptoms in
      patients with BPH. Patients and Methods: In this single blind clinical trial
      study, 90 patients diagnosed with BPH and LUTS, based on international prostate
      standard survey (IPSS) were divided into three groups. The first group was
      received oral capsule of P. harmala, the second group was administered tamsulosin
      with oral P. harmala seed and the third group was received tamsulosin drug and
      they were evaluated after 4 weeks. Results: The results showed that the
      difference between mean scores of IPSS was significant after the intervention
      (P=0.001). Besides, the mean of IPSS in the three groups was significantly
      different (P=0.001) (the first group 41.9+/-5.3, the second group 21.0+/-4.4 ,the
      third group 16.5+/-3.7 respectively). However, after the intervention, patients
      in the second group had the lowest average on most indicators of IPSS but the
      difference was only significant about urinary frequency, nocturia and
      intermittency(P<0.05). Conclusion: Application of Peganum harmala seed can be
      useful in reducing urinary symptoms in patients with BPH.

PMID- 28497090
TI  - Association between prostate specific antigen levels and coronary artery
      angioplasty.
AB  - Introduction: Prostate-specific antigen (PSA) is a protein, whose serum levels
      changes during various physiologic and pathologic situations. Recently, the
      relationship between PSA and cardiologic disorders has been assessed. Objectives:
      The purpose of this study was to assess the association of percutaneous coronary
      intervention (PCI) complications with PSA serum levels. Patients and Methods: In
      this study, 100 eligible patients undergoing PCI were included. The total PSA
      serum values were analyzed pre- and post-procedure. The association between PSA
      levels with age, gender, inflammatory (C-reactive protein [CRP] and white blood
      cell [WBC]), cardiogenic (troponin, CK-MB, echocardiography and angiography
      results), and nephrology (creatinine) properties was investigated. Results:
      Changes in the level of PSA pre- and post-PCI was not significant (P=0.2).
      However, based on the pathology, patients with acute coronary syndrome (ACS) had
      a significant difference in the levels of PSA compared to cases of stable
      ischemic heart disease (SIHD) (P=0.008). Moreover, the effect of gender on the
      changes in PSA level following PCI was conclusive. There was no association
      between the direct effect of PCI parameters or PCI complications on PSA level
      changes. Conclusion: The results showed that PSA levels were affected by the
      etiology of cardiac disorders instead of therapeutic methods like PCI.

PMID- 28497091
TI  - Restless leg syndrome in chronic hemodialysis patients in Mashhad hemodialysis
      centers.
AB  - Introduction: Restless leg syndrome (RLS) is a sensory motor disorder. Patients
      with this syndrome have serious and uncontrollable desire to move their legs,
      which is mostly due to an uncomfortable feeling intensified when they are
      motionless. It may be a genetic disorder or secondary to iron deficiency,
      neurodegenerations, pregnancy, some drugs and severe kidney diseases. Objectives:
      This study was designed to find out the prevalence and its risk factors of RLS in
      hemodialysis patients. Patients and Methods: This multicenter cross-sectional
      study was done on 260 hemodialysis patients. The prevalence of RLS was measured
      using International Restless Legs Syndrome Study Group (IRLSSG)'s RLS
      Questionnaire (RLSQ). Potential risk factors for RLS including underlying cause
      of chronic renal failure, duration on dialysis, biochemical tests, dialysis
      adequacy, and erythropoietin and also venofer dosage in recent month and
      demographic data were also evaluated. Results: The prevalence of RLS was 55%
      including 59.4% males and 40.6% females. Their mean age of RLS patients and their
      dialysis duration were significantly higher than other group (P<0.05). Their body
      mass index (BMI) and serum calcium were significantly higher (P<0.05). However
      erythropoietin dosage and serum hemoglobin level were lower in RLS patients
      (P<0.05). Significant predictors of RLS were history of diabetes mellitus (DM),
      hypertension (HTN), smoking (P<0.05). There was not significant relation between
      RLS and dialysis adequacy, serum intact parathyroid hormone (iPTH), urea,
      ferritin and venofer dosage (P>0.05). Conclusion: According to the results, RLS
      is a common disorder in hemodialysis patients which can affect strongly on their
      life. So particular attention and sooner diagnosis of RLS in high risk patients
      for better management is necessary.

PMID- 28497092
TI  - The relationship between dialysis adequacy and serum uric acid in dialysis
      patients; a cross-sectional multi-center study in Iranian hemodialysis centers.
AB  - Introduction: Uric acid is one of the most significant uremic toxins accumulating
      in chronic renal failure patients treated with standard dialysis. Its clearance
      has not any exact relation with urea and creatinine clearance. Objectives: The
      aim of this study was to investigate the relationship between adequacy of
      dialysis and serum level of uric acid in dialysis patients of some dialysis
      centers in Iran. Patients and Methods: In this study 1271 hemodialysis patients
      who have been treated for more than 3 months were evaluated. Their information
      and examinations from their files in all over the country were gathered and
      analyzed using SPSS versin18.0. Results: In this study, a significant
      relationship between dialysis duration and serum level of uric acid was not
      detected, however, a significant relationship between patients Kt/V and uric acid
      (R=0.43, P=0.029) was seen. Patients who had higher adequacy of dialysis had a
      higher level of plasma uric acid. Conclusion: For better controlling of plasma
      uric acid level of hemodialysis patients, increasing of the adequacy of dialysis
      or its duration is not effective. Other modalities of decreasing of serum uric
      acid like, changing diet or lifestyle or medical therapy may be necessary.

PMID- 28497093
TI  - Association between abnormal serum free light chains ratio and known prognostic
      factors in lymphoma; a nephrology viewpoint.
AB  - Introduction: The serum immunoglobulin free light chain (FLC) assay quantities of
      free kappa (kappa) and lambda (lambda) light chains. This assay has prognostic
      value in plasma cell proliferative disorders. There are limited data on serum FLC
      in B-cell malignancies. Objectives: The aim of this study was to compare the
      known prognostic factors in non-Hodgkin's lymphoma of the type B-cell and Hodgkin
      disease with an abnormal secretion amount of light chains in these lymphomas.
      Patients and Methods: The association of pretreatment FLC and FLC ratio
      (kappa:lambda) with previously known prognostic factors for lymphoma such as the
      international prognostic index (IPI) and B symptoms were evaluated in 50 patients
      with Hodgkin's and non-Hodgkin's lymphoma. IPI is a prognostic score given based
      on the clinical variables including age, disease stage, serum LDH and extra-nodal
      involvement. Elevated FLC and an abnormal kappa:lambda ratio was defined based on
      the previous publications. Results: The prevalence of abnormal FLC ratio was 38%
      in all patients and 40.9% in patients with diffuse large B-cell lymphoma.
      Abnormal FLC ratio was significantly associated with IPI (P=0.04) and B symptoms
      (P=0.02) in both groups of the patients with Hodgkin's and non-Hodgkin's
      lymphoma. The stage of the disease in Hodgkin's lymphoma patients showed a
      significant relationship with the abnormal FLC ratio (P=0.04). Presence of the B
      symptoms in patients with Hodgkin's lymphoma had a modest but not statistically
      significant association with the abnormal FLC ratio (P=0.07). Conclusion:
      Abnormal FLC ratio as a new potent prognostic biomarker has a significant
      association with IPI which is the most common clinical tool used to predict
      outcome in lymphoma patients. Since there is a need for developing a reliable and
      quantitative prognostic biomarker for lymphoma, evaluation of the independent
      effect of the abnormal serum FLC ratio is suggested to be considered in future
      prospective studies. The result of these studies will also be useful for
      nephrologists, while serum immunoglobulin FLC is capable to damage kidney.

PMID- 28497095
TI  - Case Reports: Stories Worth Telling in Today's Bone and Joint Literature.

PMID- 28497094
TI  - An update on diabetic kidney disease, oxidative stress and antioxidant agents.
AB  - Diabetes mellitus is a metabolic disease that is defined by relative or absolute
      deficiency of insulin secretion. Diabetic kidney disease seems to be one of the
      most frequent complications of diabetes mellitus. Based on evidence, increased
      free-radical formation and/or diminished antioxidant defenses induce oxidative
      stress that is implicated in the pathogenesis of diabetic kidney disease. It is
      evident that diabetic state induces oxidative stress through different signaling
      pathways as well as reactive oxygen species (ROS) formation that attributes to
      the activation of various downstream signaling cascade leading to structural the
      way to structural and functional changes in kidney.

PMID- 28497096
TI  - Patient Complaints Emphasize Non-Technical Aspects of Care at a Tertiary Referral
      Hospital.
AB  - BACKGROUND: Patient concerns represent opportunities for improvement in
      orthopaedic care. This study's objective is to identify the nature and prevalence
      of unsolicited patient complaints regarding orthopaedic care at a tertiary
      referral hospital. The primary null hypothesis that there are no demographic
      factors associated with complaint types was tested. Secondarily we determined if
      the overall complaint number and types differed by year. METHODS: Complaints to
      the hospital ombudsperson by orthopaedic patients between January 1997 and June
      2013 were reviewed. All 1118 complaints were categorized: access and
      availability, humaneness and disrespect, communication, expectations of care and
      treatment, distrust, billing and research. RESULTS: Patients between 40 and 60
      years of age filed the most complaints in all categories except distrust (more
      common in patients over age 80) and research. Women were slightly more likely to
      address access and availability, humaneness, disrespect, and billing compared to
      men. The overall number of complaints peaked in 1999. The most common issue was
      access and availability followed by communication, and humaneness/disrespect.
      CONCLUSION: Half of concerns voiced by patients addressed interpersonal issues.
      The largest category was related to access and availability. Quality improvement
      efforts can address technology to improve access and availability as well as
      empathy and communication strategies.

PMID- 28497097
TI  - A Randomized Controlled Pilot Study of Educational Techniques in Teaching Basic
      Arthroscopic Skills in a Low-income Country.
AB  - BACKGROUND: Little is known about how to introduce complex technologies like
      arthroscopy into low-income countries. Thus, we compared low- versus high
      resource intensive methods of teaching basic arthroscopic skills in a randomized
      controlled trial in Haiti. METHODS: Forty-eight Haitian orthopaedic surgeons and
      residents attending an orthopaedic conference in Haiti were block randomized to
      receive instruction through a composite video (Control) or a composite video plus
      hands-on teaching with an expert visiting surgeon (Intervention). A low-fidelity
      surgical simulator tested visualization and triangulation skills. Participants
      completed a pre- and post-test where the goal was to sequentially tap the most
      numbers in 2.5 minutes. Outcome metrics included highest tapped number, number of
      errors, visualization loss, and number of lookdowns. Multivariate linear
      regression was used to confirm randomization and compare outcomes between groups.
      RESULTS: Seventy-five percent of initially randomized attendees participated with
      similar attrition rates between both groups. All participants who performed a pre
      test completed a post-test. In terms of highest tapped number, treatment and
      control groups significantly improved compared to pre-test scores, with mean
      improvement of 3.2% (P=0.007) and 2.2% (P=0.03), respectively. Improvement
      between treatment and control groups was not statistically different (P=0.4). No
      statistically significant change was seen with regard to other metrics.
      CONCLUSION: We describe a protocol to introduce basic arthroscopic skills in a
      low-income country using a low-resource intensive teaching method. However, this
      method of learning may not be optimal given the failure to improve in all outcome
      measures.

PMID- 28497098
TI  - Gravity Reduction View: A Radiographic Technique for the Evaluation and
      Management of Weber B Fibula Fractures.
AB  - BACKGROUND: While various radiographic parameters and application of
      manual/gravity stress have been proposed to elucidate instability for Weber B
      fibula fractures, the prognostic capability of these modalities remains unclear.
      Determination of anatomic positioning of the mortise is paramount. We propose a
      radiographic technique, the Gravity Reduction View (GRV), which helps elucidate
      non-anatomic positioning and reducibility of the mortise. METHODS: The patient is
      positioned lateral decubitus with the injured leg elevated on a holder with the
      fibula directed superiorly. The x-ray cassette is placed posterior to the heel,
      with the beam angled at 15 degrees  of internal rotation to obtain a mortise
      view. Our proposed treatment algorithm is based upon the measurement of the
      medial clear space (MCS) on the GRV versus the static mortise view (and in
      comparison to the superior clear space (SCS)) and is based on reducibility of the
      MCS. A retrospective review of patients evaluated utilizing the GRV was
      performed. RESULTS: 26 patients with Weber B fibula fractures were managed
      according to this treatment algorithm. Mean age was 50.57 years old (range:18-81,
      SD=19). 17 patients underwent operative treatment and 9 patients were initially
      treated nonoperatively. 2 patients demonstrated late displacement and were
      treated surgically. Using this algorithm, at a mean follow-up of 26 weeks, all
      patients had a final MCS that was less than the SCS (final mean MCS 2.86 mm vs.
      mean SCS of 3.32) indicating effectiveness of the treatment algorithm.
      CONCLUSIONS: The GRV is a radiographic view in which deltoid competency,
      reducibility and initial positioning of the mortise are assessed by comparing a
      static mortise view with the appearance of the mortise on the GRV. We have
      proposed a treatment algorithm based on the GRV that we found it useful in our
      patients in guiding treatment and achieving anatomic mortise alignment.

PMID- 28497099
TI  - Acetabular Fractures in the Senior Population- Epidemiology, Mortality and
      Treatments.
AB  - BACKGROUND: Management of acetabular fractures in the senior population can be
      one of the most challenging injuries to manage. Furthermore, treating surgeons
      have a paucity of information to guide the treatment in this patient population.
      THE PURPOSE OF THIS STUDY WAS TO DETERMINE: (1) demographic and epidemiologic
      data, (2) mortality rates for nonoperative compared to operative management at
      different time points, (3) common fracture configurations, and (4) fracture
      fixation strategies in senior patients treated with acetabular fractures.
      METHODS: Retrospective review of prospectively gathered data at a Level I trauma
      center over a five-year period. 1123 acetabular fractures were identified. 156 of
      them were for patients over the age of 65 (average age of 78). RESULTS: Falls and
      motor vehicle accidents accounted for the two most common mechanisms of injury.
      82% of patients had significant medical comorbidities. 51 patients (33%) died
      within one year, in which 75% of them died within 90 days of their acetabular
      fracture. 84% of the deceased patients, i.e. from the group of 51 patients, had
      non-operative treatment. For patients treated with traction alone, there was a
      79% one-year mortality and 50% mortality rate within 90 days. Within the entire
      cohort, 70% had either an associated both-column (ABC) or anterior
      column/posterior hemitransverse (AC/PHT) fracture pattern. Fifty-seven patients
      (36.5%) underwent open reduction and internal fixation using standard reduction
      techniques and surgical implants via two main surgical exposures of ilioinguinal
      (69%) and Kocher-Langenbeck (29%). CONCLUSION: Geriatric patients with acetabular
      fractures are uncommon accounting for only 14% of all acetabular fractures.
      Patients who undergo surgery show lower mortality rates. ABC and AC/PHT fracture
      patterns are the two most common fracture patterns. Routine fixation constructs
      and implants can be used to manage these challenging fractures. Most patients are
      unable to return to their homes and instead require skilled nursing facility
      during their convalescence.

PMID- 28497100
TI  - Does Tranexamic Acid Reduce Bleeding during Femoral Fracture Operation?
AB  - BACKGROUND: Proximal Femoral shaft fractures are commonly associated with marked
      blood loss which can lead to postoperative acute anemia and some other
      complications. Tranexamic acid (TA) is an antifibrinolytic medication that
      reduces intra-and postoperative blood loss and transfusion requirements during
      some elective surgeries. The aim of this study is to evaluate the effect of
      intravenous Tranexamic acid (TA) on intraoperative blood loss and a subsequent
      need for transfusion in patients who were undergoing surgery for femoral shaft
      fractures in trauma setting. METHODS: Thirty-eight ASA grade I-II patients
      undergoing proximal femoral shaft fracture surgery with intra medullary nailing
      were included in this double blind randomized controlled clinical trial. They
      were allocated into two groups. Group I, the intervention group with eighteen
      patients received 15 mg/kg (TA) via intravenous infusion before surgical
      incision. Patients in the placebo group received an identical volume of normal
      saline. Hemoglobin level was measured four hours before and after the surgeries.
      Postoperative blood loss and hemoglobin change as well as transfusion rates and
      volumes were compared between the two groups. RESULTS: Mean Percentage fall in
      hemoglobin after surgery were 1.75+/-0.84 and 2.04+/-1.9 in the study and placebo
      groups, respectively (P=0.570). Hemoglobin loss was higher in the placebo group.
      Transfusion rates was lower in TA group (5.6%) compared to the placebo group
      (30%) (P=0.06). No significant difference in The Allowable Blood Loss during the
      surgery was found between the two groups (P=0.894). CONCLUSION: Preoperative
      treatment with TA reduces postoperative blood loss and the need for blood
      transfusion during traumatic femoral fracture operation.

PMID- 28497101
TI  - Prognostic Factors Affecting the Results of Modified Thompson Quadricepsplasty
      for the Treatment of Extension Contracture of the Knee.
AB  - BACKGROUND: Knee extension contracture is a disabling complication after
      fractures around the knee. In this study we aimed to study factors influencing
      the outcomes of quadricepsplasty for the treatment of traumatic knee extension
      contracture. We hypothesized that there is no factor influencing the final range
      of knee motion. METHODS: In this retrospective study, we included 64 patients who
      underwent modified Thompson quadricepsplasty between 2008 to 2011 with a mean
      follow-up time of 36 months. RESULTS: The mean change in flexion was 66 degrees.
      Using Judet criteria, results were excellent in 41 patients (64%), good in 15
      (23%), fair in 4 (6%) and poor in 4 (6%). Preoperative arc of flexion, duration
      of extension contracture, number of previous surgeries on the limb, and BMI of
      the patients were independently influencing the final flexion. CONCLUSION:
      Modified Thompson quadricepsplasty is associated with high number of excellent
      and good results especially when it is performed earlier in more severe
      contractures. Preoperative arc of flexion, interval between trauma surgery and
      quadricepsplasty, the number of prior surgeries, and BMI influence the outcomes
      of quadricepsplasty.

PMID- 28497102
TI  - Use of Hardware Battery Drill in Orthopedic Surgery.
AB  - Among the power drills (Electrical/Pneumatic/Battery) used in Orthopedic surgery,
      battery drill has got several advantages. Surgeons in low resource settings could
      not routinely use Orthopedic battery drills (OBD) due to the prohibitive cost of
      good drills or poor quality of other drills. "Hardware" or Engineering battery
      drill (HBD) is a viable alternative to OBD. HBD is easy to procure, rugged in
      nature, easy to maintain, durable, easily serviceable and 70 to 75 times cheaper
      than the standard high end OBD. We consider HBD as one of the cost effective
      equipment in Orthopedic operation theatres.

PMID- 28497103
TI  - Reverse Total Shoulder Arthroplasty for the Treatment of Synovial Chondromatosis:
      A Case Report and Review of the Literature.
AB  - Synovial chondromatosis affecting the glenohumeral joint is rare. Treatment
      primarily consists of arthroscopic loose body removal and synovectomy. Shoulder
      arthroplasty has been mentioned in the literature as a treatment option for
      patients with coexisting arthritis, although the results have been underreported.
      The case of an 84-year-old man with long standing synovial chondromatosis of the
      shoulder resulting in severe degenerative disease is presented. The patient was
      treated with a reverse total shoulder arthroplasty, loose body removal, and a
      complete synovectomy. Three and six month follow up results have shown a decrease
      in the visual analogue scale for pain, improved range of motion, and no
      radiographic evidence of disease recurrence. Reverse total shoulder arthroplasty
      is a viable treatment option for synovial chondromatosis in patients with
      coexisting glenohumeral arthritis demonstrating good short term outcomes.

PMID- 28497104
TI  - Stress Fracture of the Lateral Femoral Condyle after Total Knee Arthroplasty.
AB  - BACKGROUND: This is to assess one of the rare complications after total knee
      replacement and to assess risk factors of failure. METHODS: 11 patients with
      varus knee and an average age of 67 years underwent TKA between 2005 and 2013.
      All patients returned with a sudden sharp knee pain, disability to walk and
      significant decrease in ROM about 4 to 8 weeks after surgery. Radiographic
      examination revealed a lateral femoral condylar stress fracture. RESULTS: After
      analyzing the images, we found common characteristics among all patients, which
      might be attributable to the later fracture including varus deformity>25, femoral
      component lateralization, and valgus correction. CONCLUSION: Surgeons should be
      aware of the risk factors to consider before, during, and after surgery.

PMID- 28497105
TI  - Challenges in Evaluating Sleep Disturbances in Patients with Hand and Upper
      Extremity Disease.

PMID- 28497106
TI  - Stress and Intimate Partner Aggression.
AB  - Evidence suggests that stressed couples also tend to be aggressive couples.
      Chronic external stresses interact with individuals' dispositional and regulatory
      deficiencies, resulting in a spillover of these stresses into the relationship.
      High individual stress in combination with problematic interaction styles and
      problem-solving abilities increases the likelihood of IPA. We applied the I3
      Model to better organize the instigating, impelling, and inhibiting factors and
      processes that moderate the stress-IPA association. Evidence suggests that
      certain forms of stress, such as IPA victimization, reliably instigate IPA
      perpetration, with weak inhibitory processes and impaired problem solving
      moderating the stress-IPA association. More research is needed that specifies the
      'perfect storm' of factors that increase our understanding of how, and for whom,
      stress increases IPA risk.

PMID- 28497107
TI  - NGP 555, a gamma-Secretase Modulator, Lowers the Amyloid Biomarker, Abeta42, in
      Cerebrospinal Fluid while Preventing Alzheimer's Disease Cognitive Decline in
      Rodents.
AB  - INTRODUCTION: Alzheimer's disease (AD) is defined by the progressive accumulation
      of amyloid plaques and neurofibrillary tangles in the brain which precedes
      cognitive decline by years. METHODS: Using amyloid biomarkers, chemical modeling,
      mouse behavioral models, and drug development techniques we investigate the
      properties of NGP 555, a clinical-stage gamma-secretase modulator. RESULTS: NGP
      555 shifts amyloid peptide production to the smaller, non-aggregating forms of
      amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers,
      pathology, and cognition. NGP 555 has successfully completed chemistry,
      pharmacology, toxicity, metabolism, and safety studies. DISCUSSION: Abundant data
      support Abeta42 as a target for prophylactic or early-stage intervention
      therapies in AD. The gamma-secretase modulator, NGP 555 is being actively
      developed in human clinical trials for the prevention of Alzheimer's disease with
      the overall aim to achieve an appropriate balance of potency/efficacy on reducing
      the toxic forms of amyloid versus safety.

PMID- 28497108
TI  - A meta-analysis of endoscopic ultrasound-fine-needle aspiration compared to
      endoscopic ultrasound-fine-needle biopsy: diagnostic yield and the value of
      onsite cytopathological assessment.
AB  - Background The diagnostic yield of endoscopic ultrasound (EUS) guided fine-needle
      aspiration (FNA) is variable, and partly dependent upon rapid onsite evaluation
      (ROSE) by a cytopathologist. Second generation fine-needle biopsy (FNB) needles
      are being increasingly used to obtain core histological tissue samples. Aims
      Studies comparing the diagnostic yield of EUS guided FNA versus FNB have reached
      conflicting conclusions. We therefore conducted a systematic review and meta
      analysis to compare the diagnostic yield of FNA with FNB, and specifically
      evaluating the diagnostic value of ROSE while comparing the two types of needles.
      Methods We searched several databases from inception to 10 April 2016 to identify
      studies comparing diagnostic yield of second generation FNB needles with standard
      FNA needles. Risk ratios (RR) were calculated for categorical outcomes of
      interest (diagnostic adequacy, diagnostic accuracy, and optimal quality
      histological cores obtained). Standard mean difference (SMD) was calculated for
      continuous variables (number of passes required for diagnosis). These were pooled
      using random effects model of meta-analysis to account for heterogeneity. Meta
      regression was conducted to evaluate the effect of ROSE on various outcomes of
      interest. Results Fifteen studies with a total of 1024 patients were included in
      the analysis. We found no significant difference in diagnostic adequacy [RR 0.98
      (0.91, 1.06), (I2 = 51 %)]. Although not statistically significant (P = 0.06), by
      meta-regression, in the absence of ROSE, FNB showed a relatively better
      diagnostic adequacy. For solid pancreatic lesions only, there was no difference
      in diagnostic adequacy [RR 0.96 (0.86, 1.09), (I2 = 66 %)]. By meta-regression,
      in the absence of ROSE, FNB was associated with better diagnostic adequacy (P =
      0.02). There was no difference in diagnostic accuracy [RR 0.99 (0.95, 1.03), (I2
      = 27 %)] or optimal quality core histological sample procurement [RR 0.97 (0.89,
      1.05), (I2 = 9.6 %)]. However, FNB established diagnosis with fewer passes [SMD
      0.93 (0.45, 1.42), (I2 = 84 %)]. The absence of ROSE was associated with a higher
      SMD, i. e., in the presence of an onsite pathologist, FNA required relatively
      fewer passes to establish the diagnosis than in the absence of an onsite
      pathologist. Conclusions There is no significant difference in the diagnostic
      yield between FNA and FNB, when FNA is accompanied by ROSE. However, in the
      absence of ROSE, FNB is associated with a relatively better diagnostic adequacy
      in solid pancreatic lesions. Also, FNB requires fewer passes to establish the
      diagnosis.

PMID- 28497109
TI  - Hippocampal TNFalpha Signaling Contributes to Seizure Generation in an Infection
      Induced Mouse Model of Limbic Epilepsy.
AB  - Central nervous system infection can induce epilepsy that is often refractory to
      established antiseizure drugs. Previous studies in the Theiler's murine
      encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have
      demonstrated the importance of inflammation, especially that mediated by tumor
      necrosis factor-alpha (TNFalpha), in the development of acute seizures. TNFalpha
      modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause
      increased excitatory synaptic transmission. Therefore, we hypothesized that an
      increase in TNFalpha signaling after TMEV infection might contribute to acute
      seizures. We found a significant increase in both mRNA and protein levels of
      TNFalpha and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the
      hippocampus, a brain region most likely involved in seizure initiation, after
      TMEV infection, which suggests that TNFalpha signaling, predominantly through
      TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal
      cell-surface glutamate receptor expression was also observed during acute
      seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no
      effect on acute seizures, several lines of genetically modified animals deficient
      in either TNFalpha or TNFRs had robust changes in seizure incidence and severity
      after TMEV infection. TNFR2-/- mice were highly susceptible to developing acute
      seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects
      during the acute seizure period. Taken together, the present results suggest that
      inflammation in the hippocampus, caused predominantly by TNFalpha signaling,
      contributes to hyperexcitability and acute seizures after TMEV infection.
      Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated
      effects of TNFalpha may provide antiseizure and disease-modifying effects after
      central nervous system infection.

PMID- 28497111
TI  - Investigating the Influence of Biological Sex on the Behavioral and Neural Basis
      of Face Recognition.
AB  - There is interest in understanding the influence of biological factors, like sex,
      on the organization of brain function. We investigated the influence of
      biological sex on the behavioral and neural basis of face recognition in healthy,
      young adults. In behavior, there were no sex differences on the male Cambridge
      Face Memory Test (CFMT)+ or the female CFMT+ (that we created) and no own-gender
      bias (OGB) in either group. We evaluated the functional topography of ventral
      stream organization by measuring the magnitude and functional neural size of 16
      individually defined face-, two object-, and two place-related regions
      bilaterally. There were no sex differences in any of these measures of neural
      function in any of the regions of interest (ROIs) or in group level comparisons.
      These findings reveal that men and women have similar category-selective
      topographic organization in the ventral visual pathway. Next, in a separate task,
      we measured activation within the 16 face-processing ROIs specifically during
      recognition of target male and female faces. There were no sex differences in the
      magnitude of the neural responses in any face-processing region. Furthermore,
      there was no OGB in the neural responses of either the male or female
      participants. Our findings suggest that face recognition behavior, including the
      OGB, is not inherently sexually dimorphic. Face recognition is an essential skill
      for navigating human social interactions, which is reflected equally in the
      behavior and neural architecture of men and women.

PMID- 28497110
TI  - Accumbal Cholinergic Interneurons Differentially Influence Motivation Related to
      Satiety Signaling.
AB  - Satiety, rather than all or none, can instead be viewed as a cumulative decrease
      in the drive to eat that develops over the course of a meal. The nucleus
      accumbens (NAc) is known to play a critical role in this type of value
      reappraisal, but the underlying circuits that influence such processes are
      unclear. Although NAc cholinergic interneurons (CINs) comprise only a small
      proportion of NAc neurons, their local impact on reward-based processes provides
      a candidate cell population for investigating the neural underpinnings of
      satiety. The present research therefore aimed to determine the role of NAc-CINs
      in motivation for food reinforcers in relation to satiety signaling. Through
      bidirectional control of CIN activity in mice, we show that when motivated by
      food restriction, increasing CIN activity led to a reduction in palatable food
      consumption while reducing CIN excitability enhanced food intake. These activity
      dependent changes developed only late in the session and were unlikely to be
      driven by the innate reinforcer strength, suggesting that CIN modulation was
      instead impacting the cumulative change in motivation underlying satiety
      signaling. We propose that on a circuit level, an overall increase in inhibitory
      tone onto NAc output neurons played a role in the behavioral results, as
      activating NAc-CINs led to an inhibition of medium spiny neurons that was
      dependent on nicotinic receptor activation. Our results reveal an important role
      for NAc-CINs in controlling motivation for food intake and additionally provide a
      circuit-level framework for investigating the endogenous cholinergic circuits
      that signal satiety.

PMID- 28497112
TI  - FUNCTIONAL LIMITATION AND DEPRESSIVE SYMPTOMATOLOGY: CONSIDERING PERCEIVED STIGMA
      AND DISCRIMINATION WITHIN A STRESS AND COPING FRAMEWORK.
AB  - This study examines whether perceived stigma and discrimination moderate the
      associations between functional limitation, psychosocial coping resources, and
      depressive symptoms among people with physical disabilities. Using two waves of
      data from a large community study including a representative sample of persons
      with physical disabilities (N=417), an SEM-based moderated mediation analysis was
      performed. Mediation tests demonstrate that mastery significantly mediates the
      association between functional limitation and depressive symptoms over the study
      period. Moderated mediation tests reveal that the linkage between functional
      limitation and mastery varies as a function of perceived stigma and experiences
      of major discrimination and day-to-day discrimination, however. The implications
      of these findings are discussed in the context of the stress and coping
      literature.

PMID- 28497113
TI  - Toward a Cure: Does Host Immunity Play a Role?
AB  - Three decades of research on human immunodeficiency virus (HIV) and AIDS reveal
      that the human body has developed through evolution a genome immune system
      embodying epigenetic regulation against pathogenic nucleic acid invasion. In HIV
      infection, this epigenetic regulation plays a cardinal role in HIV RNA production
      that silences HIV transcription at a molecular (RNA) level, controls viral load
      at a cellular (biological) level, and governs the viremic stage of AIDS at the
      clinical (patient) level. Even though the human genome is largely similar among
      humans and HIV is a single viral species, human hosts show significant
      differences in viral RNA levels, ranging from cell to organ to individual and
      expressed as elite controllers, posttreatment controllers, and patients with
      AIDS. These are signature biomarkers of typical epigenetic regulation whose
      importance has been shunted aside by interpreting all of AIDS pathogenesis by the
      known properties of innate and adaptive immunity. We propose that harnessing the
      host genome immune system, defined as epigenetic immunity, against HIV infection
      will lead toward a cure.

PMID- 28497114
TI  - Selectable Markers for Use in Genetic Manipulation of Extensively Drug-Resistant
      (XDR) Acinetobacter baumannii HUMC1.
AB  - Acinetobacter baumannii is one of the most antibiotic-resistant pathogens in
      clinical medicine, and extensively drug-resistant (XDR) strains are commonly
      isolated from infected patients. Such XDR strains are already resistant to
      traditional selectable genetic markers, limiting the ability to conduct
      pathogenesis research by genetic disruption. Optimization of selectable markers
      is therefore critical for the advancement of fundamental molecular biology
      techniques to use in these strains. We screened 23 drugs that constitute a broad
      array of antibiotics spanning multiple drug classes against HUMC1, a highly
      virulent and XDR A. baumannii clinical blood and lung isolate. HUMC1 is resistant
      to all clinically useful antibiotics that are reported by the clinical
      microbiology laboratory, except for colistin. Ethical concerns about
      intentionally establishing pan-resistance, including to the last-line agent,
      colistin, in a clinical isolate made identification of other markers desirable.
      We screened additional antibiotics that are in clinical use and those that are
      useful only in a lab setting to identify selectable markers that were effective
      at selecting for transformants in vitro. We show that supraphysiological levels
      of tetracycline can overcome innate drug resistance displayed by this XDR strain.
      Last, we demonstrate that transformation of the tetA (tetracycline resistance)
      and Sh ble (zeocin resistance), but not pac (puromycin resistance), resistance
      cassettes allow for selection of drug-resistant transformants. These results make
      the genetic manipulation of XDR A. baumannii strains easily achieved. IMPORTANCE
      Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug
      resistant (PDR) strains of Acinetobacter baumannii have frequently been
      characterized. The ability of A. baumannii to develop resistance to antibiotics
      is a key reason this organism has been difficult to study using genetic and
      molecular biology approaches. Here we report selectable markers that are not only
      useful but necessary for the selection of drug-resistant transformants in the
      setting of drug-resistant backgrounds. Use of these selectable markers can be
      applied to a variety of genetic and molecular techniques such as mutagenesis and
      transformation. These selectable markers will help promote genetic and molecular
      biology studies of otherwise onerous drug-resistant strains, while avoiding the
      generation of pathogenic organisms that are resistant to clinically relevant
      antibiotics.

PMID- 28497115
TI  - An Efficient, Rapid, and Recyclable System for CRISPR-Mediated Genome Editing in
      Candida albicans.
AB  - Candida albicans is the most common fungal pathogen of humans. Historically,
      molecular genetic analysis of this important pathogen has been hampered by the
      lack of stable plasmids or meiotic cell division, limited selectable markers, and
      inefficient methods for generating gene knockouts. The recent development of
      clustered regularly interspaced short palindromic repeat(s) (CRISPR)-based tools
      for use with C. albicans has opened the door to more efficient genome editing;
      however, previously reported systems have specific limitations. We report the
      development of an optimized CRISPR-based genome editing system for use with C.
      albicans. Our system is highly efficient, does not require molecular cloning,
      does not leave permanent markers in the genome, and supports rapid, precise
      genome editing in C. albicans. We also demonstrate the utility of our system for
      generating two independent homozygous gene knockouts in a single transformation
      and present a method for generating homozygous wild-type gene addbacks at the
      native locus. Furthermore, each step of our protocol is compatible with high
      throughput strain engineering approaches, thus opening the door to the generation
      of a complete C. albicans gene knockout library. IMPORTANCECandida albicans is
      the major fungal pathogen of humans and is the subject of intense biomedical and
      discovery research. Until recently, the pace of research in this field has been
      hampered by the lack of efficient methods for genome editing. We report the
      development of a highly efficient and flexible genome editing system for use with
      C. albicans. This system improves upon previously published C. albicans CRISPR
      systems and enables rapid, precise genome editing without the use of permanent
      markers. This new tool kit promises to expedite the pace of research on this
      important fungal pathogen.

PMID- 28497116
TI  - pH-Mediated Microbial and Metabolic Interactions in Fecal Enrichment Cultures.
AB  - pH and fermentable substrates impose selective pressures on gut microbial
      communities and their metabolisms. We evaluated the relative contributions of pH,
      alkalinity, and substrate on microbial community structure, metabolism, and
      functional interactions using triplicate batch cultures started from fecal slurry
      and incubated with an initial pH of 6.0, 6.5, or 6.9 and 10 mM glucose, fructose,
      or cellobiose as the carbon substrate. We analyzed 16S rRNA gene sequences and
      fermentation products. Microbial diversity was driven by both pH and substrate
      type. Due to insufficient alkalinity, a drop in pH from 6.0 to ~4.5 clustered pH
      6.0 cultures together and distant from pH 6.5 and 6.9 cultures, which experienced
      only small pH drops. Cellobiose yielded more acidity than alkalinity due to the
      amount of fermentable carbon, which moved cellobiose pH 6.5 cultures away from
      other pH 6.5 cultures. The impact of pH on microbial community structure was
      reflected by fermentative metabolism. Lactate accumulation occurred in pH 6.0
      cultures, whereas propionate and acetate accumulations were observed in pH 6.5
      and 6.9 cultures and independently from the type of substrate provided. Finally,
      pH had an impact on the interactions between lactate-producing and -consuming
      communities. Lactate-producing Streptococcus dominated pH 6.0 cultures, and
      acetate- and propionate-producing Veillonella, Bacteroides, and Escherichia
      dominated the cultures started at pH 6.5 and 6.9. Acid inhibition on lactate
      consuming species led to lactate accumulation. Our results provide insights into
      pH-derived changes in fermenting microbiota and metabolisms in the human gut.
      IMPORTANCE The human gut is a dynamic environment in which microorganisms
      consistently interact with the host via their metabolic products. Some of the
      most important microbial metabolic products are fermentation products such as
      short-chain fatty acids. Production of these fermentation products and the
      prevalence of fermenting microbiota depend on pH, alkalinity, and available
      dietary sugars, but details about their metabolic interactions are unknown. Here,
      we show that, for in vitro conditions, pH was the strongest driver of microbial
      community structure and function and microbial and metabolic interactions among
      pH-sensitive fermentative species. The balance between bicarbonate alkalinity and
      formation of fatty acids by fermentation determined the pH, which controlled
      microbial community structure. Our results underscore the influence of pH balance
      on microbial function in diverse microbial ecosystems such as the human gut.

PMID- 28497118
TI  - Novel beta-Lactamase blaARL in Staphylococcus arlettae.
AB  - Whole-genome sequencing of penicillin-resistant Staphylococcus arlettae strain
      SAN1670 from bovine mastitis milk revealed a novel beta-lactamase operon
      consisting of the beta-lactamase-encoding gene blaARL, the antirepressor-encoding
      gene blaR1ARL, and the repressor-encoding gene blaIARL. The functionality of
      blaARL was demonstrated by gene expression in Staphylococcus aureus. The blaARL
      operon was chromosomally located in SAN1670 and present in 10 additional
      unrelated strains, suggesting intrinsic penicillin resistance in S. arlettae.
      Furthermore, a GenBank search revealed more unique potential beta-lactamases in
      Staphylococcus species. IMPORTANCE Penicillins are an important group of
      antibiotics used to treat various types of infections caused by Gram-positive
      bacteria. So far, the blaZ gene was the only known beta-lactamase gene in
      staphylococci. However, other putative beta-lactamases were identified, and one
      of them was shown to be a novel functional beta-lactamase encoded by blaARL in
      Staphylococcus arlettae, further limiting treatment options.

PMID- 28497117
TI  - RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems.
AB  - The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans
      and livestock by a large number of mosquito species. RNA interference (RNAi) has
      been characterized as an important innate immune defense mechanism used by
      mosquitoes to limit replication of positive-sense RNA flaviviruses and
      togaviruses; however, little is known about its role against negative-strand RNA
      viruses such as RVFV. We show that virus-specific small RNAs are produced in
      infected mosquito cells, in Drosophila melanogaster cells, and, most importantly,
      also in RVFV vector mosquitoes. By addressing the production of small RNAs in
      adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of
      virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C.
      quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C.
      quinquefasciatus mosquitoes is similar to the described activities of RNAi in
      Aedes sp. mosquitoes. We also show that these have antiviral activity, since
      silencing of RNAi pathway effectors enhances viral replication. Moreover, our
      data suggest that RVFV does not encode a suppressor of RNAi. These findings point
      toward a significant role of RNAi in the control of RVFV in mosquitoes.
      IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is an
      emerging zoonotic mosquito-borne pathogen of high relevance for human and animal
      health. Successful strategies of intervention in RVFV transmission by its
      mosquito vectors and the prevention of human and veterinary disease rely on a
      better understanding of the mechanisms that govern RVFV-vector interactions.
      Despite its medical importance, little is known about the factors that govern
      RVFV replication, dissemination, and transmission in the invertebrate host. Here
      we studied the role of the antiviral RNA interference immune pathways in the
      defense against RVFV in natural vector mosquitoes and mosquito cells and draw
      comparisons to the model insect Drosophila melanogaster. We found that RVFV
      infection induces both the exogenous small interfering RNA (siRNA) and piRNA
      pathways, which contribute to the control of viral replication in insects.
      Furthermore, we demonstrate the production of virus-derived piRNAs in Culex
      quinquefasciatus mosquitoes. Understanding these pathways and the targets within
      them offers the potential of the development of novel RVFV control measures in
      vector-based strategies.

PMID- 28497119
TI  - Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral
      Responses.
AB  - The small interfering RNA (siRNA) pathway is a major antiviral response in
      mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA
      (piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been
      reported to be a key mediator of this response in mosquitoes, but it is not
      involved in the production of virus-specific piRNAs. Here, we show that Piwi4
      associates with members of the antiviral exogenous siRNA pathway (Ago2 and Dcr2),
      as well as with proteins of the piRNA pathway (Ago3, Piwi5, and Piwi6) in an
      Aedes aegypti-derived cell line, Aag2. Analysis of small RNAs captured by Piwi4
      revealed that it is predominantly associated with virus-specific siRNAs in
      Semliki Forest virus-infected cells and, to a lesser extent, with viral piRNAs.
      By using a Dcr2 knockout cell line, we showed directly that Ago2 lost its
      antiviral activity, as it was no longer bound to siRNAs, but Piwi4 retained its
      antiviral activity in the absence of the siRNA pathway. These results demonstrate
      a complex interaction between the siRNA and piRNA pathways in A. aegypti and
      identify Piwi4 as a noncanonical PIWI protein that interacts with members of the
      siRNA and piRNA pathways, and its antiviral activities may be independent of
      either pathway. IMPORTANCE Mosquitoes transmit several pathogenic viruses, for
      example, the chikungunya and Zika viruses. In mosquito cells, virus replication
      intermediates in the form of double-stranded RNA are cleaved by Dcr2 into 21
      nucleotide-long siRNAs, which in turn are used by Ago2 to target the virus
      genome. A different class of virus-derived small RNAs, PIWI-interacting RNAs
      (piRNAs), have also been found in infected insect cells. These piRNAs are longer
      and are produced in a Dcr2-independent manner. The only known antiviral protein
      in the PIWI family is Piwi4, which is not involved in piRNA production. It is
      associated with key proteins of the siRNA and piRNA pathways, although its
      antiviral function is independent of their actions.

PMID- 28497120
TI  - Analysis of Light- and Carbon-Specific Transcriptomes Implicates a Class of G
      Protein-Coupled Receptors in Cellulose Sensing.
AB  - In fungi, most metabolic processes are subject to regulation by light.
      Trichoderma reesei is adapted to degradation of plant cell walls and regulates
      production of the required enzymes in a manner dependent on the nutrient source
      and the light status. Here we investigated the interrelated relevance of two
      regulation levels of the transcriptome of T. reesei: light regulation and carbon
      source-dependent control. We show that the carbon source (cellulose, lactose,
      sophorose, glucose, or glycerol) is the major source of variation, with light
      having a modulating effect on transcript regulation. A total of 907 genes were
      regulated under cellulase-inducing conditions in light, and 947 genes were
      regulated in darkness, with 530 genes overlapping (1,324 in total). Only 218 of
      the 1,324 induction-specific genes were independent of light and not regulated by
      the BLR1, BLR2, and ENV1 photoreceptors. Analysis of the genomic distribution of
      genes regulated by light upon growth on cellulose revealed considerable overlap
      of light-regulated clusters with induction-specific clusters and carbohydrate
      active enzyme (CAZyme) clusters. Further, we found evidence for the operation of
      a sensing mechanism for solid cellulosic substrates, with regulation of genes
      such as swo1, cip1, and cip2 or of genes encoding hydrophobins which is related
      to the cyclic AMP (cAMP)-dependent regulatory output of ENV1. We identified class
      XIII G-protein-coupled receptors (GPCRs) CSG1 and CSG2 in T. reesei as putative
      cellulose/glucose-sensing GPCRs. Our data indicate that the cellulase regulation
      pathway is bipartite, comprising a section corresponding to transcriptional
      regulation and one corresponding to posttranscriptional regulation, with the two
      connected by the function of CSG1. IMPORTANCE In fungi, most metabolic processes
      are subject to regulation by light. For Trichoderma reesei, light-dependent
      regulation of cellulase gene expression is specifically shown. Therefore, we
      intended to unravel the relationship between regulation of enzymes by the carbon
      source and regulation of enzymes by light. Our two-dimensional analysis included
      inducing and repressing carbon sources which we used to compare light-specific
      regulation to dark-specific regulation and to rule out effects specific for a
      single carbon source. We found close connections with respect to gene regulation
      as well as significant differences in dealing with carbon in the environment in
      light and darkness. Moreover, our analyses showed an intricate regulation
      mechanism for substrate degradation potentially involving surface sensing and
      provide a basis for knowledge-based screening for strain improvement.

PMID- 28497121
TI  - Implementation of Isavuconazole in a Fluorescence-Based High-Performance Liquid
      Chromatography Kit Allowing Simultaneous Detection of All Four Currently Licensed
      Mold-Active Triazoles.
AB  - Isavuconazole (ISZ) is a newly available broad-spectrum triazole agent recently
      approved for the treatment of both invasive aspergillosis and mucormycosis. The
      aim of this study was to develop a simple and reliable method for therapeutic
      drug monitoring (TDM) of ISZ in human plasma samples. The method involves using a
      kit from ChromSystems intended for TDM of itraconazole (ITZ), posaconazole (PSZ),
      and voriconazole (VRZ) in serum/plasma for sample preparation and high
      performance liquid chromatography, using fluorescence detection with emission and
      excitation wavelengths set to 261 and 366 nm, respectively. The assay was linear
      over the ISZ concentration range of 0.2 to 20.0 mg/liter, using a 0.1-ml sample
      volume. The inter- and intraday coefficients of variation were all below 3.7%,
      whereas the accuracies ranged from 95.0 to 106.2% and the mean extraction
      recovery was 91.9%. In addition, the method worked well using four different
      Vacutainer types, with six different healthy volunteers and under a number of
      relevant storage conditions. Finally, the ISZ detection could be seamlessly
      implemented in the TDM kit for VRZ, PSZ, and ITZ, enabling simultaneous detection
      of all four triazoles. This method proved to be simple, accurate, precise, and
      well suited for routine analysis work. It has been implemented in our laboratory
      for the simultaneous quantitative analysis of ISZ, VRZ, PSZ, and ITZ for TDM and
      pharmacokinetic research. IMPORTANCE Isavuconazole is a new broad-spectrum
      triazole agent recently approved for the treatment of both invasive aspergillosis
      and mucormycosis. Currently, there is no consensus regarding the potential need
      for TDM of isavuconazole, and no therapeutic window has been defined. However, at
      the ECIL-6 meeting in 2015, it was advised that TDM is indicated in a number of
      different settings. In this study, we describe a rapid and validated isocratic
      HPLC method for fluorescence-based detection and quantification of isavuconazole
      in human plasma/serum samples. The method is simple and efficient with good
      accuracy and precision and importantly only requires a small volume of patient
      plasma/serum. Furthermore, this method is highly sensitive and selective and can
      be detected simultaneously with the three other triazoles, itraconazole,
      voriconazole, and posaconazole, without the need for expensive mass spectrometry
      equipment.

PMID- 28497122
TI  - The Microbiome-Mitochondrion Connection: Common Ancestries, Common Mechanisms,
      Common Goals.
AB  - Lynn Margulis in the 1960s elegantly proposed a shared phylogenetic history
      between bacteria and mitochondria; this relationship has since become a
      cornerstone of modern cellular biology. Yet, an interesting facet of the
      interaction between the microbiome and mitochondria has been mostly ignored, that
      of the systems biology relationship that underpins host health and longevity. The
      mitochondria are descendants of primordial aerobic pleomorphic bacteria (likely
      genus Rickettsia) that entered (literally and functionally) into a mutualistic
      partnership with ancient anaerobic microbes (likely Archaea). A stable symbiosis
      was established, given the metabolic versatility of the early mitochondria, which
      were capable of providing energy with or without oxygen, whereas nutrient
      gathering was the assumed responsibility of the host. While microbial
      relationships with single-cell protists must have occurred in the past, as they
      occur today, the evolution of multicellular organisms generated a new framework
      for symbiosis with the microbial world, taking the ancient partnership to an
      entirely new level. Cell-cell communication between microbes and single-cell
      protists was augmented through multicellularity to allow distant communication
      between the host cells and the microbiome, resulting in the development of
      complex metabolic relationships and an immune system to manage these
      interactions. Thus, the host is now the body and its resident mitochondria, and
      the microbiome is an essential supplier of metabolites that act at the level of
      mitochondria in skeletal muscle to stabilize host metabolism. We humans are
      caretakers of a profoundly vast and diverse microbiota, the majority of which
      resides in the gut. Indeed, the microbial genetic diversity of our microbiota
      outstrips our own by several orders of magnitude, and the cellular abundance is
      roughly equivalent to our somatic selves. Modern clinical science has elegantly
      highlighted the importance of the microbiome for metabolic health and well-being.
      This perspective underscores one fundamental facet of this symbiosis, the
      ancestral mitochondrion-microbiome axis.

PMID- 28497123
TI  - Functional trait diversity maximizes ecosystem multifunctionality.
AB  - Understanding the relationship between biodiversity and ecosystem functioning has
      been a core ecological research topic over the last decades. Although a key
      hypothesis is that the diversity of functional traits determines ecosystem
      functioning, we do not know how much trait diversity is needed to maintain
      multiple ecosystem functions simultaneously (multifunctionality). Here, we
      uncovered a scaling relationship between the abundance distribution of two key
      plant functional traits (specific leaf area, maximum plant height) and
      multifunctionality in 124 dryland plant communities spread over all continents
      except Antarctica. For each trait, we found a strong empirical relationship
      between the skewness and the kurtosis of the trait distributions that cannot be
      explained by chance. This relationship predicted a strikingly high trait
      diversity within dryland plant communities, which was associated with a local
      maximization of multifunctionality. Skewness and kurtosis had a much stronger
      impact on multifunctionality than other important multifunctionality drivers such
      as species richness and aridity. The scaling relationship identified here
      quantifies how much trait diversity is required to maximize multifunctionality
      locally. Trait distributions can be used to predict the functional consequences
      of biodiversity loss in terrestrial ecosystems.

PMID- 28497124
TI  - PARV4 prevalence, phylogeny, immunology and coinfection with HIV, HBV and HCV in
      a multicentre African cohort.
AB  - Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably
      by region. In sub-Saharan Africa, seroprevalence is high in the general
      population, but little is known about the transmission routes or the prevalence
      of coinfection with blood-borne viruses, HBV, HCV and HIV.  Methods: To further
      explore the characteristics of PARV4 in this setting, with a particular focus on
      the prevalence and significance of coinfection, we screened a cohort of 695
      individuals recruited from Durban and Kimberley (South Africa) and Gaborone
      (Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status.
      Results: Within these cohorts, 69% of subjects were HIV-positive. We identified
      no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive
      in 42%; seroprevalence was higher in adults (69%) compared to children (21%)
      (p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%)
      (p<0.0001), but there was no association with HBsAg status. We developed an on
      line tool to allow visualization of coinfection data
      (https://purl.oclc.org/coinfection-viz). We identified five subjects who were PCR
      positive for PARV4 genotype-3. Ex vivo CD8+ T cell responses spanned the entire
      PARV4 proteome and we propose a novel HLA-B*57:03-restricted epitope within the
      NS protein.  Conclusions: This characterisation of PARV4 infection provides
      enhanced insights into the epidemiology of infection and co-infection in African
      cohorts, and provides the foundations for planning further focused studies to
      elucidate transmission pathways, immune responses, and the clinical significance
      of this organism.

PMID- 28497125
TI  - Mapping ubiquitination sites of S. cerevisiae Mcm10.
AB  - Minichromosome maintenance protein (Mcm) 10 is a part of the eukaryotic
      replication machinery and highly conserved throughout evolution. As a multivalent
      DNA scaffold, Mcm10 coordinates the action of proteins that are indispensable for
      lagging strand synthesis, such as the replication clamp, proliferating cell
      nuclear antigen (PCNA). The binding between Mcm10 and PCNA serves an essential
      function during DNA elongation and is mediated by the ubiquitination of Mcm10.
      Here we map lysine 372 as the primary attachment site for ubiquitin on S.
      cerevisiae Mcm10. Moreover, we identify five additional lysines that can be
      ubiquitinated. Mutation of lysine 372 to arginine ablates ubiquitination of
      overexpressed protein and causes sensitivity to the replication inhibitor
      hydroxyurea in cells that are S-phase checkpoint compromised. Together, these
      findings reveal the high selectivity of the ubiquitination machinery that targets
      Mcm10 and that ubiquitination has a role in suppressing replication stress.

PMID- 28497126
TI  - Vulnerability to Depression in Youth: Advances from Affective Neuroscience.
AB  - Vulnerability models of depression posit that individual differences in trait
      like vulnerabilities emerge early in life and increase risk for the later
      development of depression. In this review, we summarize advances from affective
      neuroscience using neural measures to assess vulnerabilities in youth at high
      risk for depression due to parental history of depression or temperament style,
      as well as prospective designs evaluating the predictive validity of these
      vulnerabilities for symptoms and diagnoses of depression across development.
      Evidence from multiple levels of analysis indicates that healthy youth at high
      risk for depression exhibit abnormalities in components of the Research Domain
      Criteria (RDoC) positive valence systems, including blunted activation in the
      striatum during reward anticipation and feedback, and that some of these measures
      can be used to predict later symptoms. In addition, alterations in components of
      RDoC's negative valence systems, including neural processing of sadness, loss,
      and threat, have been observed in risk for depression, though effects appear to
      be more task and method dependent. Within the social processes domain,
      preliminary evidence indicates that neural processing of social feedback,
      including heightened reactivity to exclusion and blunted response to social
      reward, may be related to depression vulnerability. These studies indicate that
      affective neuroscience can inform understanding of developmental pathways to
      depression and identify altered emotional processing among youth at high risk. We
      provide an integrated summary of consistent findings from this literature, along
      with recommendations for future directions and implications for early
      intervention.

PMID- 28497127
TI  - Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation
      Mismatch During Mechanical Unloading of the Failing Human Heart: Implications for
      Cardiac Reloading and Conditioning.
AB  - This study sought to investigate the effects of mechanical unloading on
      myocardial energetics and the metabolic perturbation of heart failure (HF) in an
      effort to identify potential new therapeutic targets that could enhance the
      unloading-induced cardiac recovery. The authors prospectively examined paired
      human myocardial tissue procured from 31 advanced HF patients at left ventricular
      assist device (LVAD) implant and at heart transplant plus tissue from 11 normal
      donors. They identified increased post-LVAD glycolytic metabolites without a
      coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The
      increased pyruvate was not directed toward the mitochondria and the TCA cycle for
      complete oxidation, but instead, was mainly converted to cytosolic lactate.
      Increased nucleotide concentrations were present, potentially indicating
      increased flux through the pentose phosphate pathway. Evaluation of mitochondrial
      function and structure revealed a lack of post-LVAD improvement in mitochondrial
      oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic
      acid content. Finally, post-LVAD unloading, amino acid levels were found to be
      increased and could represent a compensatory mechanism and an alternative energy
      source that could fuel the TCA cycle by anaplerosis. In summary, the authors
      report evidence that LVAD unloading induces glycolysis in concert with pyruvate
      mitochondrial oxidation mismatch, most likely as a result of persistent
      mitochondrial dysfunction. These findings suggest that interventions known to
      improve mitochondrial biogenesis, structure, and function, such as controlled
      cardiac reloading and conditioning, warrant further investigation to enhance
      unloading-induced reverse remodeling and cardiac recovery.

PMID- 28497128
TI  - Innovative Therapeutics: Designer Natriuretic Peptides.
AB  - Endogenous natriuretic peptides serve as potent activators of particulate
      guanylyl cyclase receptors and the second messenger cGMP. Natriuretic peptides
      are essential in maintenance of volume homeostasis, and can be of myocardial,
      renal and endothelial origin. Advances in peptide engineering have permitted the
      ability to pursue highly innovative drug discovery strategies. This has resulted
      in designer natriuretic peptides that go beyond native peptides in efficacy,
      specificity, and resistance to enzymatic degradation. Together with recent
      improvements in peptide delivery systems, which have improved bioavailability,
      further advances in this field have been made. Therefore, designer natriuretic
      peptides with pleotropic actions together with strategies of chronic delivery
      have provided an unparalleled opportunity for the treatment of cardiovascular
      disease. In this review, we report the conceptual framework of peptide
      engineering of the natriuretic peptides that resulted in designer peptides for
      cardiovascular disease. We specifically provide an update on those currently in
      clinical trials for heart failure and hypertension, which include Cenderitide,
      ANX042 and ZD100.

PMID- 28497129
TI  - Molecular modeling of the AhR structure and interactions can shed light on ligand
      dependent activation and transformation mechanisms.
AB  - Molecular modeling has given important contributions to elucidation of the main
      stages in the AhR signal transduction pathway. Despite the lack of experimentally
      determined structures of the AhR functional domains, information derived from
      homologous systems has been exploited for modeling their structure and
      interactions. Homology models of the AhR PASB domain have provided information on
      the binding cavity and contributed to elucidate species-specific differences in
      ligand binding. Molecular Docking simulations of the ligand binding process have
      given insights into differences in binding of diverse agonists, antagonists, and
      selective AhR modulators, and their application to virtual screening of large
      databases of compounds have allowed identification of novel AhR ligands. Recently
      available structural information on protein-protein and protein-DNA complexes of
      other bHLH-PAS systems has opened the way for modeling the AhR:ARNT dimer
      structure and investigating the mechanisms of AhR transformation and DNA binding.
      Future research directions should include simulation of the protein dynamics to
      obtain a more reliable description of intermolecular interactions involved in
      signal transmission.

PMID- 28497131
TI  - Guest Editorial: Implementation science for oral health promotion.

PMID- 28497130
TI  - Not all that glitters is gold: A guide to critical appraisal of animal drug
      trials in epilepsy.
AB  - Preclinical studies have produced numerous drugs with antiseizure properties
      which currently are the standard of care in clinical care. A third of the human
      population with epilepsy still continues having seizures despite the ongoing
      discoveries. The recognized clinical gaps of care that need to be addressed are
      the identification of antiepileptogenic and disease modifying treatments,
      treatments for refractory seizures or for seizures and epilepsies with limited or
      unsatisfactory treatments, such as early life epileptic encephalopathies. In this
      invited review, we provide a historical summary of the international efforts to
      re-evaluate the strategies adopted in preclinical epilepsy therapy discovery
      studies. We discuss issues that may impact the quality, interpretation and
      validation of preclinical studies and their translation to successful therapies
      for humans affected with epilepsy. These include the selection of animal models
      and the study design, research practices that affect rigor, such as appropriate
      use of statistics and reporting of study methods and results, their validation
      across models, labs and preclinical-clinical studies, the need to harmonize
      research methods and outcome assessment, and the importance to improve
      translation to clinically appropriate situations. The epilepsy research community
      is incrementally adopting collaborative research, including consortia or
      multicenter studies to meet these needs. Improving the infrastructure that can
      support these efforts will be instrumental in the future success.

PMID- 28497132
TI  - Three generations of zirconia: ?From veneered to monolithic. Part II.
AB  - This article presents the historical development of the different generations of
      zirconia and their range of indications, from veneered to monolithic zirconia
      restorations. While Part I concentrated on detailed information about the
      development of zirconia for dental use and the mechanical and optical properties,
      Part II deals with the resulting guidelines for working with the relevant
      generations by summarizing the correct cementation procedure. Furthermore, this
      part also focuses on translucency measurements for better characterization and
      understanding of the different materials. The results obtained from measuring
      light transmission and contrast ratio are compared and discussed in detail, with
      the aid of clinical photographs. Finally, the reader is given practice-relevant
      recommendations for different areas of clinical use of the zirconia generations
      along with advice on how to process them appropriately.

PMID- 28497133
TI  - Development and testing of satisfaction questionnaires for patients with
      removable dental prostheses.
AB  - OBJECTIVE: To develop and test self-administered satisfaction questionnaires for
      patients with removable dental prostheses (RDPs) in the German language. METHOD
      AND MATERIALS: A three-phase methodology was used. A pilot questionnaire was
      developed in phase one. At the end of phase two, the final version of the
      questionnaires were reached. In phase three, 192 questionnaires were distributed
      to evaluate the psychometric properties of the final version of the
      questionnaires. Construct validity, content validity from the patients'
      perspective, and questionnaire reliability were estimated. RESULTS: At the end of
      phase two, the final versions of the questionnaires were defined as instruments
      with good face validity. At the end of phase three, content validity from the
      patients' perspective was assessed and found to be good. Exploratory factor
      analysis identified a one-factor model for each questionnaire. Consequently, each
      questionnaire was summed to create a single index. Internal consistency of the
      indexes was assessed using Cronbach's alpha and found to be excellent (alpha >
      0.9). A high repeatability of all the items was identified through a test-retest.
      Intra-class correlation coefficient (ICC) values ranged from 0.80 to 0.99.
      CONCLUSION: The questionnaires and indexes are valid and highly reliable
      instruments, and can be used to measure patient satisfaction with RDPs.

PMID- 28497134
TI  - Enhanced planar perovskite solar cells with efficiency exceeding 16% via reducing
      the oxygen vacancy defect state in titanium oxide electrode.
AB  - In this work, the influence of oxygen vacancy defect (OVD) in compact titanium
      oxide (c-TiO2) on the performance of planar perovskite solar cells (p-PSCs) is
      investigated, and the possible mechanisms are also proposed. To meet our
      objective, anatase c-TiO2 thin films with various OVD concentrations are prepared
      by changing the oxygen flux during the DC magnetron sputtering process and are
      characterized by the intensity of defect signals in the X-ray photoelectron
      spectra. We conclude that abundant OVDs can trigger an obviously increased
      majority carrier accumulation zone at the metal oxide/perovskite interface and
      enhanced capacitance, thereby greatly deteriorating photogenerated carrier
      collection efficiency. A detailed analysis of the study results also reveals that
      the presence of OVD in the bulk and surface of c-TiO2 can slow down electronic
      carrier transport and lower its electron quasi-Fermi level under illumination,
      leading to the detrimental charge recombination in p-PSCs. Furthermore, we report
      a remarkably enhanced p-PSC efficiency via preparing c-TiO2 using high oxygen
      flux and subsequent ultraviolet ozone treatment. As a consequence, repeatable
      power conversion efficiency (PCE) is propelled to as high as 16.62%, coupled with
      negligible hysteresis and increased stability. These results provide a
      significant implication for further perfecting efficient and stable p-PSCs for
      their record efficiency.

PMID- 28497135
TI  - Unscrambling micro-solvation of -COOH and -NH groups in neat dimethyl sulfoxide:
      insights from 1H-NMR spectroscopy and computational studies.
AB  - Dimethyl sulfoxide (DMSO) has a significant, multi-faceted role in medicine,
      pharmacy, and biology as well as in biophysical chemistry and catalysis. Its
      physical properties and impact on biomolecular structures still attract major
      scientific interest, especially the interactions of DMSO with biomolecular
      functional groups. In the present study, we shed light on the "isolated"
      carboxylic (-COOH) and amide (-NH) interactions in neat DMSO via1H NMR studies
      along with extensive theoretical approaches, i.e. molecular dynamics (MD)
      simulations, density functional theory (DFT), and ab initio calculations, applied
      on model compounds (i.e. acetic and benzoic acid, ethyl acetamidocyanoacetate).
      Both experimental and theoretical results show excellent agreement, thereby
      permitting the calculation of the association constants between the studied
      compounds and DMSO molecules. Our coupled MD simulations, DFT and ab initio
      calculations, and NMR spectroscopy results indicated that complex formation is
      entropically driven and DMSO molecules undergo multiple strong interactions with
      the studied molecules, particularly with the -COOH groups. The combined
      experimental and theoretical techniques unraveled the interactions of DMSO with
      the most abundant functional groups of peptides (i.e. peptide bonds, side chain
      and terminal carboxyl groups) in high detail, providing significant insights on
      the underlying thermodynamics driving these interactions. Moreover, the developed
      methodology for the analysis of the simulation results could serve as a template
      for future thermodynamic and kinetic studies of similar systems.

PMID- 28497136
TI  - Local chemical potential, local hardness, and dual descriptors in temperature
      dependent chemical reactivity theory.
AB  - In this work we establish a new temperature dependent procedure within the grand
      canonical ensemble, to avoid the Dirac delta function exhibited by some of the
      second order chemical reactivity descriptors based on density functional theory,
      at a temperature of 0 K. Through the definition of a local chemical potential
      designed to integrate to the global temperature dependent electronic chemical
      potential, the local chemical hardness is expressed in terms of the derivative of
      this local chemical potential with respect to the average number of electrons.
      For the three-ground-states ensemble model, this local hardness contains a term
      that is equal to the one intuitively proposed by Meneses, Tiznado, Contreras and
      Fuentealba, which integrates to the global hardness given by the difference in
      the first ionization potential, I, and the electron affinity, A, at any
      temperature. However, in the present approach one finds an additional temperature
      dependent term that introduces changes at the local level and integrates to zero.
      Additionally, a tau-hard dual descriptor and a tau-soft dual descriptor given in
      terms of the product of the global hardness and the global softness multiplied by
      the dual descriptor, respectively, are derived. Since all these reactivity
      indices are given by expressions composed of terms that correspond to products of
      the global properties multiplied by the electrophilic or nucleophilic Fukui
      functions, they may be useful for studying and comparing equivalent sites in
      different chemical environments.

PMID- 28497137
TI  - Identification of two novel antioxidant peptides from edible bird's nest
      (Aerodramus fuciphagus) protein hydrolysates.
AB  - Edible bird's nest (EBN) is widely consumed as a delicacy and traditional
      medicine amongst the Chinese. In the present study, for the first time, the
      antioxidant properties of an EBN pepsin-trypsin hydrolysate of the swiftlet
      species Aerodramus fuciphagus and its ultrafiltration fractions were
      investigated. Thirteen peptides with molecular weights between 514.29 and 954.52
      Da were identified in the EBN fraction with the use of mass spectrometry. Two
      novel pentapeptides Pro-Phe-His-Pro-Tyr and Leu-Leu-Gly-Asp-Pro, corresponding to
      f134-138 and f164-168 of cytochrome b of A. fuciphagus, indicated the highest
      ORAC values of 14.95 and 14.32 MUM of TE MUM-1 peptide, respectively. Both
      purified peptides showed resistance against simulated gastrointestinal proteases.
      In addition, both peptides had no in vitro cytotoxicity on human lung MRC-5 cells
      and prevented human liver carcinoma HepG2 cellular damage caused by hydroxyl
      radicals. Therefore, it is suggested that EBN protein hydrolysates are a good
      source of natural antioxidants and could be applied as nutraceutical compounds.

PMID- 28497138
TI  - A Ni2P modified Ti4+ doped Fe2O3 photoanode for efficient solar water oxidation
      by promoting hole injection.
AB  - Nickel phosphide (Ni2P) was used as an excellent water oxidation cocatalyst for
      photoelectrochemical (PEC) water splitting, which could significantly promote the
      hole injection efficiency and suppress the back reaction of water oxidation over
      a Ti4+ doped Fe2O3 photoanode.

PMID- 28497139
TI  - LiMCO3 (M = K, Rb, Cs): a series of mixed alkali carbonates with large
      birefringence.
AB  - By the hydrothermal method, two new mixed alkali carbonates, LiRbCO3 and LiCsCO3
      were synthesized for the first time. Both compounds crystallize in the monoclinic
      space group P21/n, and exhibit similar wave like [LiCO3]infinity layers connected
      by Rb-O and Cs-O bonds, respectively. They not only possess low melt temperature
      and wide spectral transmittance range, but also have relatively large
      birefringence confirmed by first principles calculations. In the mixed alkali
      carbonates system of LiMCO3 (M = K, Rb, Cs), with the increase of atomic radius
      of the alkali metal, the birefringence is reduced from 0.11 in LiKCO3 to 0.09 in
      LiCsCO3, while the refractivity is increasing. The increasing refractivity and
      decreasing birefringence can be interpreted by the enhancement of orbital
      hybridization resulting from the reduced C-O bond length and weakened structural
      anisotropy, respectively.

PMID- 28497140
TI  - Critical behavior in tetragonal antiperovskite GeNFe3 with a frustrated
      ferromagnetic state.
AB  - Tetragonal GeNFe3 has a second-order ferromagnetic (FM) to paramagnetic
      transition at 76 K. Our integrated investigations indicate that the ground FM
      state is frustrated and the tetragonal symmetry is retained below 550 K based on
      the results of variable temperature X-ray diffraction. Critical behavior was
      analyzed by a systematic bulk magnetization study. The estimated critical
      exponents by three different methods (modified Arrott plot, the Kouvel-Fisher
      method, and critical isotherm analysis) conformably suggest that long-range
      magnetic coupling described by mean-field (MF) theoretical model is dominant in
      GeNFe3. The experimental M-T-H data collapse into two independent branches
      according to the scaling equations m = f+/-(h) with the renormalized
      magnetization m = epsilon-betaM(H, epsilon) and the magnetic field h = Hepsilon
      (beta+gamma). The exchange distance is estimated as J(r) ~ r-4.8 on the basis of
      the beta and gamma values, which lies between the long-range MF model (r-4.5) and
      the short-range 3D Heisenberg (3DH) model (r-5). Our results indicate that the
      competition between local magnetic moments of iron 3d electronic state and
      itinerant covalent interactions of N-Fe bonds should be responsible for critical
      behavior in this system.

PMID- 28497141
TI  - Hierarchical bicontinuous structure of redox-active organic composites and their
      enhanced electrochemical properties.
AB  - The hierarchical bicontinuous structure of redox-active organic composites of
      crystalline quinone derivatives and conductive polymers was generated through
      simultaneous etching of the crystal and polymerization of the monomer. The
      bicontinuous composite showed enhanced electrochemical properties as a result of
      the smooth redox reaction of its components.

PMID- 28497142
TI  - Methyl-functionalized MoS2 nanosheets with reduced lattice breathing for enhanced
      pseudocapacitive sodium storage.
AB  - Sodium ion batteries (SIBs) possess the potential to realize low-cost and large
      scale energy storage due to the abundance of sodium. However, the large ionic
      radius of sodium often leads to sluggish kinetics and large volume change,
      limiting the further development of SIBs. Layered MoS2, with a large interlayer
      distance, is a promising intercalation anode material for SIBs. In this work, we
      report the synthesis of methyl-functionalized MoS2 (M-MoS2) nanosheets through a
      facile second solvothermal method. During the second solvothermal treatment, the
      pristine MoS2 is mostly converted from the 2H to 1T phase and the interlayer
      distance is expanded from 0.65 to 0.80 nm. When evaluated as the anode for SIBs,
      the M-MoS2 exhibits superior cycling stability and rate capability. Kinetic
      analysis shows that the capacity is mainly contributed from a pseudocapacitive
      process. Ex situ XRD shows that the M-MoS2 exhibits inhibited lattice breathing
      and thus reduced volume change during cycling. This work demonstrates that the M
      MoS2 is a promising candidate for pseudocapacitive sodium storage.

PMID- 28497143
TI  - 18F-Fluoroform: a 18F-trifluoromethylating agent for the synthesis of SCF218F
      aromatic derivatives.
AB  - Herein the synthesis of various SCF218F-containing derivatives is reported by a
      transition metal-free process. By using HCF218F, readily generated from a bench
      stable difluoromethyl sulfonium salt, various aromatic disulfides were easily
      converted into the desired radiolabelled trifluoromethylthiolated compounds in
      the presence of a base. This protocol allowed the formation of the SCF218F
      containing aromatic derivatives in good to excellent radiochemical yields. This
      process was also extended to the corresponding selenium derivative.

PMID- 28497144
TI  - Colloidal synthesis of urchin-like Fe doped NiSe2 for efficient oxygen evolution.
AB  - The search for highly efficient non-precious metal electrocatalysts toward the
      oxygen evolution reaction (OER) is extremely essential for renewable energy
      systems. Here, we report the colloidal synthesis of Fe doped NiSe2, which
      functions as a high-performance electrocatalyst for the OER in alkaline solution.
      The NiFeSe catalysts are composed of urchin-like dendrites with a high number of
      active sites, which could provide fast transportation of electrons and
      electrolytes, and facile release of the evolved O2 bubbles during the OER
      catalysis. Benefitting from this unique urchin-like structure and strong electron
      interaction between Fe, Ni, and Se, the Ni1.12Fe0.49Se2 catalyst exhibits
      excellent electrocatalytic activity and high durability toward the OER in
      alkaline solution, with an overpotential of 227 mV at a current density of 10 mA
      cm-2, which is, to the best of our knowledge, higher than most of the reported
      selenide-based electrocatalysts.

PMID- 28497145
TI  - A dendritic core-shell Cu@PtCu alloy electrocatalyst resulting in an enhanced
      electron transfer ability and boosted surface active sites for an improved
      methanol oxidation reaction.
AB  - We reported the design of a core-shell Cu@PtCu electrocatalyst consisting of
      dendritic PtCu alloy branches assembling on Cu core nanocrystals. The Cu@PtCu
      electrocatalyst shows superior electrocatalytic performance toward a methanol
      oxidation reaction. Its specific activity and mass activity can reach 3.56 mA cm
      2 and 1568 mA mgPt-1, which are 4.8 and 7.1 times higher than those of a
      commercial 20% Pt/C catalyst.

PMID- 28497147
TI  - Relativistic effects in metallocorroles: comparison of molybdenum and tungsten
      biscorroles.
AB  - The homoleptic sandwich compounds - Mo and W biscorroles - have afforded a novel
      platform for experimental studies of relativistic effects. A 200 mV difference in
      reduction potential and a remarkable 130 nm shift of a near-IR spectral feature
      have been identified as manifestations of relativistic effects on the properties
      of these complexes.

PMID- 28497148
TI  - Efficient synthesis of cyclic P-stereogenic phosphinamides from acyclic chiral
      precursors via radical oxidative intramolecular aryl C-H phosphinamidation.
AB  - We present a highly efficient method for the synthesis of cyclic P-stereogenic
      phosphinamides via the Ce(IV)-promoted radical oxidative aryl C-H
      phosphinamidation of acyclic P-stereogenic phosphinamides. The new protocol
      provides a useful platform for the versatile synthesis of various potentially
      useful P-stereogenic compounds.

PMID- 28497146
TI  - The effect of the buffer solution on the adsorption and stability of horse heart
      myoglobin on commercial mesoporous titanium dioxide: a matter of the right
      choice.
AB  - Despite the numerous studies on the adsorption of different proteins onto
      mesoporous titanium dioxide and indications on the important role of buffer
      solutions in bioactivity, a systematic study on the impact of the buffer on the
      protein incorporation into porous substrates is still lacking. We here studied
      the interaction between a commercial mesoporous TiO2 and three of the most used
      buffers for protein incorporation, i.e. HEPES, Tris and phosphate buffer. In
      addition, this paper analyzes the adsorption of horse heart myoglobin (hhMb) onto
      commercial mesoporous TiO2 as a model system to test the influence of buffers on
      the protein incorporation behavior in mesoporous TiO2. N2 sorption analysis, FT
      IR and TGA/DTG measurements were used to evaluate the interaction between the
      buffers and the TiO2 surface, and the effect of such an interaction on hhMb
      adsorption. Cyclic voltammetry (CV) and electron paramagnetic resonance (EPR)
      were used to detect changes in the microenvironment surrounding the heme. The
      three buffers show a completely different interaction with the TiO2 surface,
      which drastically affects the adsorption of myoglobin as well as its structure
      and electrochemical activity. Therefore, special attention is required while
      choosing the buffer medium to avoid misguided evaluation of protein adsorption on
      mesoporous TiO2.

PMID- 28497149
TI  - A convenient and clean synthetic method for borasiloxanes by Pd-catalysed
      reaction of silanols with diborons.
AB  - Selective O-borylation of silanols with diborons took place in the presence of Pd
      catalysts to give the corresponding boryl silyl ethers in high yields.

PMID- 28497151
TI  - Oxygen diffusion in ceria doped with rare-earth elements.
AB  - We examine the effects of the dopant type and the dopant distribution on the ion
      diffusion in ceria doped with rare-earth elements (Pr, Nd, Pm, Sm, Eu, and Gd).
      Diffusion is simulated by means of a Kinetic Monte Carlo method using input
      transition rates derived from diffusion barriers calculated in the framework of
      density functional theory (DFT). Based on diffusion simulations, we discuss the
      characteristics of the dopants in terms of the diffusion barriers, and study
      oxygen ion trajectories for different dopants and distributions. Our simulations
      show a trend of increasing ion diffusivity with increasing atomic number for all
      distributions.

PMID- 28497150
TI  - A near-room-temperature organic-inorganic hybrid ferroelectric:
      [C6H5CH2CH2NH3]2[CdI4].
AB  - An organic-inorganic hybrid compound, [C6H5CH2CH2NH3]2[CdI4], exhibits a
      reversible ferroelectric phase transition at 301/297 K. Switchable dielectric
      constant, second harmonic generation, and pyroelectricity were synchronously
      observed accompanied by the order-disorder phase transition. This finding
      promotes research on molecular ferroelectrics to search for promising
      multifunctional switching materials at near room temperature.

PMID- 28497153
TI  - Catalytic dehydrogenative dual functionalization of ethers: dealkylation
      oxidation-bromination accompanied by C-O bond cleavage via aerobic oxidation of
      bromide.
AB  - Catalytic dehydrogenative dual functionalization (DDF) of ethers via oxidation,
      dealkylation, and alpha-bromination by the aerobic oxidation of bromide was
      developed to obtain the corresponding alpha-bromo ketones in high yields. In
      particular, the reaction of substituted tetrahydrofurans as cyclic ethers
      provided 3,3-dibromo tetrahydrofuran-2-ols in high yields selectively through the
      double alpha-bromination.

PMID- 28497152
TI  - The sedoheptulose 7-phosphate cyclases and their emerging roles in biology and
      ecology.
AB  - Covering up to: 1999-2016This highlight covers a family of enzymes of growing
      importance, the sedoheptulose 7-phosphate cyclases, initially of interest due to
      their involvement in the biosynthesis of pharmaceutically relevant secondary
      metabolites. More recently, these enzymes have been found throughout Prokarya and
      Eukarya, suggesting their broad potential biological roles in nature.

PMID- 28497154
TI  - Hot off the press.
AB  - A personal selection of 32 recent papers is presented covering various aspects of
      current developments in bioorganic chemistry and novel natural products such as
      macrophilone A from Macrorhynchia philippina.

PMID- 28497155
TI  - Influence of washing and quenching in profiling the metabolome of adherent
      mammalian cells: a case study with the metastatic breast cancer cell line MDA-MB
      231.
AB  - Metabolome characterisation is a powerful tool in oncology. To obtain a valid
      description of the intracellular metabolome, two of the preparatory steps are
      crucial, namely washing and quenching. Washing must effectively remove the
      extracellular media components and quenching should stop the metabolic activities
      within the cell, without altering the membrane integrity of the cell. Therefore,
      it is important to evaluate the efficiency of the washing and quenching solvents.
      In this study, we employed two previously optimised protocols for simultaneous
      quenching and extraction, and investigated the effects of a number of washing
      steps/solvents and quenching solvent additives, on metabolite leakage from the
      adherent metastatic breast cancer cell line MDA-MB-231. We explored five washing
      protocols and five quenching protocols (including a control for each), and
      assessed for effectiveness by detecting ATP in the medium and cell morphology
      changes through scanning electron microscopy (SEM) analyses. Furthermore, we
      studied the overall recovery of eleven different metabolite classes using the GC
      MS technique and compared the results with those obtained from the ATP assay and
      SEM analysis. Our data demonstrate that a single washing step with PBS and
      quenching with 60% methanol supplemented with 70 mM HEPES (-50  degrees C)
      results in minimum leakage of intracellular metabolites. Little or no
      interference of PBS (used in washing) and methanol/HEPES (used in quenching) on
      the subsequent GC-MS analysis step was noted. Together, these findings provide
      for the first time a systematic study into the washing and quenching steps of the
      metabolomics workflow for studying adherent mammalian cells, which we believe
      will improve reliability in the application of metabolomics technology to study
      adherent mammalian cell metabolism.

PMID- 28497157
TI  - Concentration-dependent circularly polarized luminescence (CPL) of chiral N,N'
      dipyrenyldiamines: sign-inverted CPL switching between monomer and excimer
      regions under retention of the monomer emission for photoluminescence.
AB  - Herein, an unprecedented switching of circularly polarized luminescence (CPL) is
      described for chiral 4,6-bis(1-(pyren-1-ylamino)propyl)dibenzo[b,d]furan (1). The
      CPL band of chiral diamine 1, which contains two pyrene rings, can be switched
      between the monomer and excimer emission regions under concomitant inversion of
      the handedness, simply by changing the concentration of the fluorophore. In
      contrast, the maximum photoluminescence (PL) intensity is always observed in the
      monomer region, regardless of the concentration. The reversal of the intensity
      ratio of monomer and excimer emission between PL and CPL was attributed to a
      stronger CPL (|gem| = ~3-4 * 10-3) contribution from the minor excimer component,
      which should exhibit an efficient chiral environment around the dimeric pyrenes.

PMID- 28497156
TI  - Tumor suppressors microRNA-302d and microRNA-16 inhibit human glioblastoma
      multiforme by targeting NF-kappaB and FGF2.
AB  - Glioblastoma multiforme (GBM) is a highly malignant cancer in the brain with a
      median survival time of approximately one year. However, the mechanisms
      underlying GBM development and occurrence are poorly understood. Recently, miRNAs
      were reported to play important roles in GBM. We performed microRNA profiling by
      comparing the human GBM cell line T98G and control cell line HCN1A. MicroRNA
      assays, PCR and Western blot analysis were performed to detect the expressions of
      microRNAs, mRNAs and proteins of target genes, respectively. Cell migration and
      invasion assays were conducted. A murine in situ xenograft tumor model was used
      to evaluate tumor growth in vivo. Glioblastoma tissues were examined to
      investigate the clinical relevance of our findings. MiR-302d and miR-16 levels
      were found to be decreased in T98G cells. MiR-302d and miR-16 inhibited the
      expressions of p65 and FGF2, respectively, by binding to the 3'-UTR of their
      mRNAs. Over-expression of miR-302d and miR-16 inhibited T98G cell migration and
      invasion in vitro, and tumorigenesis in the xenograft tumor mouse model in vivo,
      by suppressing p65 and FGF2. Negative correlations between miR-302d and p65 and
      between miR-16 and FGF2 were observed in patient glioblastoma tissues. MiR-302d
      and miR-16 inhibit tumorigenesis by down-regulating p65 and FGF2, which
      potentially contributes to the treatment of glioblastoma with clinical relevance.

PMID- 28497158
TI  - Intralesional interleukin-2 for unresectable mucosal melanoma refractory to
      nivolumab.

PMID- 28497159
TI  - Current status of chimeric antigen receptor engineered T cell-based and immune
      checkpoint blockade-based cancer immunotherapies.
AB  - Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells
      (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have
      lately shown remarkable success in certain tumor types. CAR-T cell-based
      therapies targeting CD19 can now induce durable remissions as well as prolong
      disease-free survival of patients with CD19 positive treatment refractory B cell
      malignancies and ICI-based therapies with humanized monoclonal antibodies against
      the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1
      ligand, PD-L1, can now achieve durable remissions as well as prolongation of life
      of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non
      small cell cancers. Most importantly, these immuno-therapeutic treatment
      modalities have raised the possibility of achieving long-term "containment" as
      well as "cures" for certain types of cancer. While this represents major advances
      in cancer immunotherapy, both modalities come with considerable toxicities,
      including fatalities. Although more work will be needed to bring CAR-T cell-based
      therapies to the bedside for most major cancers and a good deal more will be
      needed to make ICI-alone or in combination with other treatment modalities-work
      more consistently and across most major cancers, these two treatment modalities
      stand out as superb examples of successful translation of bench research to the
      bedside as well as represent real progress in the field of cancer immunotherapy.

PMID- 28497160
TI  - Spinal osteoid osteoma: efficacy and safety of radiofrequency ablation.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and complications
      of CT-guided radiofrequency ablation (RFA) of spinal osteoid osteoma (OO).
      MATERIALS AND METHODS: Between 2002 and 2012, a total of 61 patients (46 male and
      15 female, mean age 26.4 +/- 12.7 years) were subjected to RFA for spinal OO. The
      diagnosis of OO was made after a period of pain and symptoms of 20.6 +/- 14.4
      months. RFA was performed under conscious sedation and local analgesia. Clinical
      symptoms were evaluated at 3, 6, and12 months, and at the end of the time of the
      present investigation. Mean follow-up was 41.5 +/- 7.1 months. RESULTS: The
      primary efficacy of RFA, complete regression of symptoms, was obtained in 57 out
      of 61 patients (93.4%). Four out of 61 (6.5%) patients showed a relapse of OO
      (after 3 months); 2 out of 4 were subjected to a second RFA, the remaining ones
      were subjected to surgery. There was one complication (case of lower limb
      paresthesia for 30 days after the ablation) and one possible complication (a disc
      herniation). CONCLUSION: CT-guided RFA is an excellent treatment for spinal OO.
      Our data suggest that this procedure should be considered for the first stage of
      therapy for this disease.

PMID- 28497161
TI  - Outcomes in diabetic foot ulcer patients with isolated T2 marrow signal
      abnormality in the underlying bone: should the diagnosis of "osteitis" be changed
      to "early osteomyelitis"?
AB  - OBJECTIVE: To evaluate the variability of clinical treatment and outcomes based
      on reporting of diabetic foot ulcer MRI findings of adjacent marrow T2
      hyperintensity with normal T1 signal. MATERIALS AND METHODS: A retrospective
      review was conducted of 46 MRI examinations evaluating diabetic foot ulcers that
      demonstrated normal T1 marrow signal, but T2 marrow hyperintensity deep to the
      ulcer. The cohort was divided based on MRI report impressions into three groups;
      "osteitis without osteomyelitis" (OW), "osteitis but cannot exclude early
      osteomyelitis" (OCEO) and "early osteomyelitis" (EO). Patient demographics (age,
      gender) and accessory MRI findings of ulcer and sinus tract depth were recorded.
      Initial clinical assessment and medical treatment (route and duration of
      antibiotics), healing versus disease progression and histology or microbiology
      results were recorded. RESULTS: The isolated marrow T2 signal hyperintensity was
      reported as OW in 12 patients, OCEO in 18, and EO in 16. No statistical
      difference in clinical assessment was demonstrated between the OW, OCEO, and EO
      groups. Pathological condition was available in 15 patients within 0-7 days (mean
      2.4 days) of the MRI examination, with 14 (93%) of these positive for
      osteomyelitis by histopathology or positive cultures. Initial diagnosis of or
      progression to osteomyelitis was shown in 28 patients (61%). CONCLUSION:
      Treatment of suspected osteomyelitis is heavily determined by clinical factors.
      Patients who initially demonstrate only T2 marrow signal abnormality under a
      diabetic ulcer are eventually diagnosed as osteomyelitis in 61% of cases and
      deserve aggressive treatment as early osteomyelitis when meeting clinical
      parameters.

PMID- 28497162
TI  - Cadaver embalming fluid for surgical training courses: modified Larssen solution.
AB  - PURPOSE: 10% Formalin (F10)-fixed cadavers have disadvantages such as disturbing
      smell, mucosal irritation, discoloration and rigidity. We aimed to determine a
      suitable, simple and cost-effective embalming method that preserves color,
      texture, pliability and flexibility of the tissues for a long time without a
      disturbing smell and mucosal irritation. The embalmed cadavers were expected to
      be durable against environmental effects, utilizable for multiple and repetitive
      surgical trainings and instrumentations. METHODS: Eight male (six intact, two
      autopsied bodies) and four female (three intact and one imported trunk) human
      cadavers were preserved with modified Larssen solution (MLS). Preserved bodies
      were kept in the deep freezers at -18/-20  degrees C. Bodies were allowed to thaw
      at room temperature 3 days prior to use. They were used in postgraduate hands-on
      courses for several medical disciplines. Each course lasted at least 1 day and
      during this period the bodies were stayed at room temperature. Assessments of 30
      trainers and 252 trainees were collected during the courses. Additionally, the
      organoleptic characteristics of the fresh frozen (FF), preserved with MLS and F10
      fixed cadavers were compared. RESULTS: The colors of muscles, fasciae, fatty
      tissue, nerves and vessels were evaluated and life-like tissues of MLS cadavers
      were impressive. There were no obvious or disturbing smell and sign of
      putrefaction of the MLS cadavers. CONCLUSIONS: MLS is a sustainable and
      relatively affordable soft cadaver embalming method. Its application is same as
      in other conventional methods and does not need new equipment. This article
      indicates the success of the MLS method in human cadavers.

PMID- 28497163
TI  - [Alternative approaches in thyroid surgery].
AB  - In thyroid surgery multiple different cervical minimally invasive (partly
      endoscopically assisted) and extracervical endoscopic (partly robot-assisted)
      approaches have been developed in the last 20 years. The aim of all these
      alternative approaches to the thyroid gland is optimization of the cosmetic
      result. The indications for the use of alternative and conventional approaches
      are principally the same. Important requirements for the use of alternative
      methods are nevertheless a broad experience in conventional thyroid operations of
      the thyroid and adequate patient selection under consideration of the size of the
      thyroid and the underlying pathology. Contraindications for the use of
      alternative approaches are a large size of the thyroid gland including local
      symptoms, advanced carcinomas, reoperations and previous radiations of the
      anterior neck. The current article gives an overview of the clinically
      implemented alternative approaches for thyroid surgery. Of those the majority
      must still be considered as experimental. The alternative approaches to the
      thyroid gland can be divided in cervical minimally invasive, extracervical
      endosopic (robot-assisted) and transoral operations (natural orifice transluminal
      endoscopic surgery, NOTES). Since conventional thyroid operations are
      standardized procedures with low complication rates, alternative approaches to
      the thyroid gland are considered critically in Germany. The request for a perfect
      cosmetic result should not overweigh patients' safety. Only a few alternative
      approaches (e. g. MIVAT, RAT) can yet be considered as a safe addition in
      experienced hands in highly selected patients.

PMID- 28497165
TI  - Linear relationship between lateralization of the bicipital groove and humeral
      retroversion and its link with the biepicondylar humeral line. Anatomical study
      of seventy cadaveric humerus scans.
AB  - INTRODUCTION: Morphological studies of the humerus have shown that the position
      of the bicipital groove varies with the individual and the retroversion of the
      humeral head. Depending on the authors, these two parameters are independent or
      associated. This study evaluated the relationship between the humeral head axis
      and its retroversion and the bicipital groove relative to the humeral
      biepicondylar line. MATERIALS AND METHODS: Seventy cadaveric humeri were scanned
      to obtain 3D reconstructions. Views of the 3D reconstruction from above showed
      the bicondylar line, the bicipital groove and the humeral head on a single image.
      After measuring the humeral retroversion angle and the bicipital groove angle
      relative to the bicondylar line, we assessed the relationship between these two
      angles with Pearson's correlation coefficient. RESULTS: Pearson's correlation
      coefficient indicated a significant linear correlation between the angle of the
      groove and the angle of humeral retroversion based on the 70 cadaveric humeral
      bones (the p-value was 7.510-7, the correlation coefficient was -0.5515, and the
      95% confidence interval was (-0.6962; -0.3636)). Our study thus demonstrates that
      the less lateralized the bicipital groove is, the greater the humeral
      retroversion will be. CONCLUSION: We demonstrated a linear relationship between
      humeral head retroversion and bicipital groove lateralization. Within our
      reliability interval, this relationship can be used in clinical practice to
      evaluate retroversion without resorting to CT of the entire humerus.

PMID- 28497164
TI  - Metformin prevents ischaemic ventricular fibrillation in metabolically normal
      pigs.
AB  - AIMS/HYPOTHESIS: Metformin is the drug most often used to treat type 2 diabetes.
      Evidence suggests that metformin may reduce mortality of individuals with type 2
      diabetes, but the mechanism of such an effect is unknown and outcomes of
      metformin treatment in people without diabetes have not been determined. If
      metformin favourably affected mortality of non-diabetic individuals, it might
      have even broader therapeutic utility. We evaluated the effect of metformin on
      myocardial energetics and ischaemic ventricular fibrillation (VF) in
      metabolically normal pigs. METHODS: Domestic farm pigs were treated with
      metformin (30 mg kg-1 day-1 orally for 2-3 weeks; n = 36) or received no
      treatment (n = 37). Under anaesthesia, pigs underwent up to 90 min low-flow
      regional myocardial ischaemia followed by 45 min of reperfusion. Pigs were
      monitored for arrhythmia, monophasic action potential morphology, haemodynamics
      and myocardial substrate utilisation, AMP-activated protein kinase (AMPK)
      phosphorylation activity and ATP concentration. RESULTS: Death due to VF occurred
      in 12% of pigs treated with metformin compared with 50% of untreated controls (p
      = 0.03). The anti-fibrillatory effect of metformin was associated with
      attenuation of action potential shortening in ischaemic myocardium (p = 0.02) and
      attenuation of the difference in action potential duration between ischaemic and
      non-ischaemic regions (p < 0.001) compared with untreated controls. Metformin had
      no effect on myocardial contractile function, oxygen consumption, or glucose or
      lactate utilisation. During ischaemia, however, metformin treatment amplified the
      activation of AMPK and preserved ATP concentration in myocardium compared with
      untreated controls (each p < 0.05). CONCLUSIONS/INTERPRETATION: Chronic treatment
      of metabolically normal pigs with metformin at a clinically relevant dose reduces
      mortality from ischaemic VF. This protection is associated with preservation of
      myocardial energetics during ischaemia. Maintenance of myocardial ATP
      concentration during ischaemia is likely to prevent action potential shortening,
      heterogeneity of repolarisation, and propensity for lethal arrhythmia. The
      findings suggest that metformin might be protective in non-diabetic individuals
      with coronary heart disease.

PMID- 28497166
TI  - Biomechanical evaluation of straight antegrade nailing in proximal humeral
      fractures: the rationale of the "proximal anchoring point".
AB  - PURPOSE: Varus failure is one of the most common failure modes following surgical
      treatment of proximal humeral fractures. Straight antegrade nails (SAN)
      theoretically provide increased stability by anchoring to the densest zone of the
      proximal humerus (subchondral zone) with the end of the nail. The aim of this
      study was to biomechanically investigate the characteristics of this "proximal
      anchoring point" (PAP). We hypothesized that the PAP would improve stability
      compared to the same construct without the PAP. METHODS: Straight antegrade
      humeral nailing was performed in 20 matched pairs of human cadaveric humeri for a
      simulated unstable two-part fracture. RESULTS: Biomechanical testing, with
      stepwise increasing cyclic axial loading (50-N increments each 100 cycles) at an
      angle of 20 degrees  abduction revealed significantly higher median loads to
      failure for SAN constructs with the PAP (median, 450 N; range, 200-1.000 N)
      compared to those without the PAP (median, 325 N; range, 100-500 N; p = 0.009).
      SAN constructs with press-fit proximal extensions (endcaps) showed similar median
      loads to failure (median, 400 N; range, 200-650 N), when compared to the
      undersized, commercially available SAN endcaps (median, 450 N; range, 200-600 N;
      p = 0.240). CONCLUSIONS: The PAP provided significantly increased stability in
      SAN constructs compared to the same setup without this additional proximal
      anchoring point. Varus-displacing forces to the humeral head were superiorly
      reduced in this setting. This study provides biomechanical evidence for the
      "proximal anchoring point's" rationale. Straight antegrade humeral nailing may be
      beneficial for patients undergoing surgical treatment for unstable proximal
      humeral fractures to decrease secondary varus displacement and thus potentially
      reduce revision rates.

PMID- 28497167
TI  - Results of arthroscopic Bankart repair with Hill-Sachs remplissage for anterior
      shoulder instability.
AB  - PURPOSE: The aim of this study was to evaluate mid-term outcomes of Bankart
      repair with Hill-Sachs remplissage (BHSR) and to highlight prognostic factors of
      failure. METHODS: Thirty-four patients operated on for anterior shoulder
      instability with BHSR were enrolled in a prospective non-randomised study.
      Clinical and radiographic evaluation was performed at 1.5, three, six months and
      yearly thereafter. Outcome measures included Rowe and Walch-Duplay score.
      RESULTS: At mean follow-up of 35 months (24-63), the Rowe and Walch-Duplay scores
      reached respectively 92.7 and 88.2 points. The mean deficit in external rotation
      was 6 degrees  in ER1 and 1 degrees  in ER2 (p = 0.4, p = 0.9 respectively). Five
      patients (14.7%) had a recurrence of instability and three others had a
      persistent anterior apprehension. In the failure group, the Hill-Sachs lesion was
      deeper (26% vs 19% of the humeral diameter; p = 0.04) and range of motion at 1.5
      months postoperatively was greater. Age at surgery, pre-operative instability
      severity index score (ISIS), hyperlaxity, type and level of sport, amount of
      glenoid bone loss had no correlation with failure rate. CONCLUSIONS: The rate of
      failure at mid-term follow-up of BHSR was higher than commonly reported. The
      premature recovery of range of motion seems to be a clinical sign of failure at
      follow-up. Moreover, in case of deep Hill-Sachs lesion (>20%) an alternative
      procedure should be considered. LEVEL OF EVIDENCE: Level IV.

PMID- 28497168
TI  - Relationship between geographical origin, seed size and genetic diversity in faba
      bean (Vicia faba L.) as revealed by SSR markers.
AB  - Faba bean (Vicia faba L.) is an important legume species because of its high
      protein and starch content. Broad bean can be grown in different climatic
      conditions and is an ideal rotation crop because of the nitrogen fixing bacteria
      in its roots. In this work, 255 faba bean germplasm accessions were characterized
      using 32 SSR primers which yielded 302 polymorphic fragments. According to the
      results, faba bean individuals were divided into two main groups based on the
      neighbor-joining algorithm (r = 0.91) with some clustering based on geographical
      origin as well as seed size. Population structure was also determined and agreed
      with the dendrogram analysis in splitting the accessions into two subpopulations.
      Analysis of molecular variance (AMOVA) revealed high levels of within population
      genetic variation. Genetic similarity and geographical proximity were related
      with separation of European accessions from African and Asian ones.
      Interestingly, there was no significant difference between landrace (38%) and
      cultivar (40%) diversity indicating that genetic variability has not yet been
      lost due to breeding. A total of 44 genetically well-characterized faba bean
      individuals were selected for a core collection to be further examined for yield
      and nutritional traits.

PMID- 28497169
TI  - Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor
      cell clusters and macrometastases: displaying heterogeneity and crater-like
      structure on inner layer.
AB  - PURPOSE: Pancreatic cancer 3D in vitro models including multicellular tumor
      spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor
      spheroid, and organotypic models provided powerful platforms to mimic in vivo
      tumor. Recent work supports that circulating tumor cell (CTC) clusters are more
      efficient in metastasis seeding than single CTCs. The purpose of this study is to
      establish 3D culture models which can mimic single CTC, monoclonal CTC clusters,
      and the expansion of macrometastases. METHODS: Seven pancreatic ductal
      adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop
      and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid
      formation assay, immunoblotting, and literature review were performed to
      investigate molecular biomarkers and the morphological characteristics of
      pancreatic tumor spheroids. RESULTS: Single cells experienced different growth
      patterns to form SCTS, like signet ring-like cells, blastula-like structures, and
      solid core spheroids. However, golf ball-like hollow spheroids could also be
      detected, especially when DanG and Capan-1 cells were cultivated with fibroblast
      conditioned medium (p < 0.05). The size of golf ball-like hollow spheroids hardly
      grew after getting matured. Only DanG and Capan-1 could establish SCTS- and MCTS
      derived hollow spheroids using hanging drop plates and ultra-low attachment
      plates. Other PDA cell lines could also establish tumor spheroid with hanging
      drop plates by adding methylated cellulose. Tumor spheroids derived from
      pancreatic cancer cell line DanG possessed asymmetrically distributed
      proliferation center, immune-checkpoint properties. beta-catenin, Ki-67, and F
      actin were active surrounding the crater-like structure distributing on the inner
      layer of viable rim cover of the spheroids, which was relevant to well
      differentiated tumor cells. CONCLUSIONS: It is possible to establish 3D CTC
      cluster models from homogenous PDA cell lines using hanging drop and ultra-low
      attachment plates. PDA cell line displays its own intrinsic properties or
      heterogeneity. The mechanism of formation of the crater-like structure as well as
      golf ball-like structure needs further exploration.

PMID- 28497170
TI  - High systemic and testicular thermolytic efficiency during heat tolerance test
      reflects better semen quality in rams of tropical breeds.
AB  - This study aimed to assess the capacity of Morada Nova (MN) and Santa Ines (SIN)
      rams to maintain body and testicular homeothermy under thermal challenge. For 5
      days in the summer, 16 males (SIN = 7 and MN = 9) underwent a heat tolerance
      test, i.e., period 1-animals maintained in the shade (11 to 12 h); period 2
      animals exposed to sunlight (12 to 13 h); and period 3-animals returned to the
      shade (13 to 14 h). The respiratory rate, heart rate, rectal temperature, and
      infrared surface temperatures (IRT) of the trunk, back, eyeball, and testicles
      were assessed in each period. The index of capacity of tolerance to insolation
      (ICTI), which indicates the animals' level of adaptability, was calculated for
      each animal. Semen quality and testicular parenchyma integrity were assessed
      before and after the thermal challenge. Statistical analyses were performed at 5%
      significance. In period 1, the variables had baseline values for both genotypes.
      In period 2, the variables involved in thermolysis significantly increased (P <
      0.05), which matches a thermal discomfort situation. In period 3, the variables
      returned to baseline values and some values were lower than those in period 1.
      Semen quality and testicular parenchyma integrity suffered no negative effects
      with the thermal challenge. IRT ocular and IRT testicular were positively
      correlated (P < 0.05). It is concluded that MN and SIN rams had efficient
      thermolytic mechanisms that favor preserving gonadal functionality. The animals
      were considered resilient to a thermal challenge. In addition, infrared
      thermography was an efficient tool to verify body and testicular
      thermoregulation.

PMID- 28497171
TI  - Measuring facial cooling in outdoor windy winter conditions: an exploratory
      study.
AB  - Winter clothing provides insulation for almost all of a person's body, but in
      most situations, a person's face remains uncovered even in cold windy weather.
      This exploratory study used thermal imagery to record the rate of cooling of the
      faces of volunteers in a range of winter air temperatures and wind speeds.
      Different areas of the faces cooled at different rates with the areas around the
      eyes and neck cooling at the slowest rate, and the nose and cheeks cooling at the
      fastest rate. In all cases, the faces cooled at an approximately logarithmic
      decay for the first few minutes. This was followed by a small rise in the
      temperature of the face for a few minutes, which was then followed by an
      uninterrupted logarithmic decay. Volunteers were told to indicate when their face
      was so cold that they wanted to end the test. The total amount of time and the
      facial temperature at the end of each trial were recorded. The results provide
      insight into the way faces cool in uncontrolled, outdoor winter conditions.

PMID- 28497173
TI  - Identifying Effective and Sustainable Measures for Community-Based Environmental
      Monitoring.
AB  - Resource development projects typically result in monitoring programs that fail
      to fully consider the values and participation of surrounding communities. Also,
      monitoring protocols for single environmental values can be insufficient for
      addressing the cumulative impacts of resource development. Community-based
      environmental monitoring (CBEM) has emerged as a way to meaningfully include
      local citizens in the decision-making process and assessment of the development
      of natural resources. Our research explored how to develop effective and
      sustainable CBEM. Interviews were conducted with staff from 15 CBEM programs
      established across Canada to identify criteria of what constitutes effective
      CBEM. Results demonstrate that CBEM offers an effective, locally adapted, and
      culturally applicable approach to facilitate community participation in natural
      resource management and to track environmental change. Benefits of CBEM include:
      locally relevant monitoring protocols, inclusion of cumulative impacts, better
      informed decision-making, and increased awareness and collaboration amongst
      community, governments, and proponents. Challenges associated with CBEM are cost,
      capacity, longevity, distribution of results, and establishing credibility. This
      research validates the use of CBEM for improving resource management.

PMID- 28497174
TI  - Stability assessment of a new antithrombotic small peptide, Arg-Gly-Asp-Trp-Arg
      (RGDWR), and its derivative.
AB  - OBJECTIVE: To assess the stabilities of Arg-Gly-Asp-Trp-Arg (RGDWR, designated as
      RWR), a new patented antithrombotic small peptide, and its derivative with omega
      aminocaprylic acid on its N-terminus (omegaRWR). RESULTS: RWR in rat plasma was
      decreased by between 32 and 48% after 4 h incubation on ice, indicating its
      instability in plasma. In contrast, omegaRWR in plasma remained at 96-107%.
      Concentration changes were within 6.2% for omegaRWR after storage in various
      conditions. omegaRWR is therefore stable in rat plasma, as well as under
      different storage methods. Furthermore, omega-aminocaprylic acid added onto the
      RWR peptide did not affect its antiplatelet aggregation activity. CONCLUSIONS: A
      novel small peptide, omegaRWR, has been developed with a good stability for
      possible antithrombotic use.

PMID- 28497175
TI  - Characterization and role of a 2',3'-cyclic phosphodiesterase from Deinococcus
      radiodurans.
AB  - OBJECTIVES: A 2',3'-cyclic phosphodiesterase gene (drCPDase) has been
      characterized from Deinococcus radiodurans and is involved in the robust
      resistance of this organism. RESULTS: Cells lacking 2',3'-cyclic
      phosphodiesterase gene (drCPDase) showed modest growth defects and displayed
      increased sensitivities to high doses of various DNA-damaging agents including
      ionizing radiation, mitomycin C, UV and H2O2. The transcriptional level of
      drCPDase increased after H2O2 treatment. Additional nucleotide monophosphate
      partially recovered the phenotype of drCPDase knockout cells. Complementation of
      E. coli with drCPDase resulted in enhanced H2O2 resistance. CONCLUSIONS: The
      2',3'-cyclic phosphodiesterase (drCPDase) contributes to the extreme resistance
      of D. radiodurans and is presumably involved in damaged nucleotide
      detoxification.

PMID- 28497177
TI  - Critical appraisal of health-state utility values used in breast cancer-related
      cost-utility analyses.
AB  - PURPOSE: To review the data sources of health-state utility values (HSUVs), as
      well as their elicitation and use, in 140 breast cancer-related cost-utility
      analyses (CUAs), and to provide a critical appraisal of these. METHODS: A
      checklist was developed to guide the process of the critical appraisal. It is
      divided into three parts: the data source (three questions), elicitation method
      (four questions), and use (ten questions) of HSUVs in CUAs. Two independent
      reviewers performed the data extraction. A consensus was reached in case of
      disagreements. Data sources were categorized as "original study," "derived from
      the literature," or "other." RESULTS: The data source of HSUVs was always
      specified. When HSUVs were derived from the literature (90% of cases), the
      authors referred to a median number of two references as data sources. The
      critical appraisal of the elicitation of HSUVs in CUAs revealed considerable
      variability in terms of the quality of the reporting of the data source selection
      of HSUV. More details were provided by authors when HSUVs were elicited from an
      original study rather than derived from the literature. The use of HSUVs elicited
      from an original study was generally better described in terms of the checklist
      than were those derived from the literature. CONCLUSIONS: Based on the developed
      checklist, we were able to highlight the challenges that authors are facing when
      trying to adequately report HSUV used in CUAs. Our proposed checklist offers a
      good starting point for encouraging more explicit and comprehensive reporting of
      HSUVs in CUAs.

PMID- 28497172
TI  - Deep intronic mutations and human disease.
AB  - Next-generation sequencing has revolutionized clinical diagnostic testing. Yet,
      for a substantial proportion of patients, sequence information restricted to
      exons and exon-intron boundaries fails to identify the genetic cause of the
      disease. Here we review evidence from mRNA analysis and entire genomic sequencing
      indicating that pathogenic mutations can occur deep within the introns of over 75
      disease-associated genes. Deleterious DNA variants located more than 100 base
      pairs away from exon-intron junctions most commonly lead to pseudo-exon inclusion
      due to activation of non-canonical splice sites or changes in splicing regulatory
      elements. Additionally, deep intronic mutations can disrupt transcription
      regulatory motifs and non-coding RNA genes. This review aims to highlight the
      importance of studying variation in deep intronic sequence as a cause of
      monogenic disorders as well as hereditary cancer syndromes.

PMID- 28497176
TI  - Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2
      positive gastric cancer: a phase II trial and biomarker study (WJOG7212G).
AB  - BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for
      advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia.
      However, its efficacy and safety when combined with trastuzumab therapy for human
      epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains
      unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice
      daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus
      trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The
      primary end point was the response rate, and the secondary end points included
      progression-free survival, overall survival, safety, and serum biomarker levels.
      RESULTS: Forty-four patients were enrolled. The response rate, progression-free
      survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9
      months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse
      events were neutropenia (30%) and anorexia (25%). A significantly higher response
      rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5
      months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14)
      compared with low (n = 17) pretreatment serum neuregulin 1 levels. CONCLUSIONS:
      Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor
      response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum
      neuregulin 1 might be associated with the efficacy of this treatment regimen.

PMID- 28497178
TI  - Optimization of production of C-phycocyanin and extracellular polymeric
      substances by Arthrospira sp.
AB  - The key factors influencing the production of C-phycocyanin (C-PC) and
      extracellular polymeric substances (EPS) by photoautotrophic culture of
      Arthrospira sp. were optimized using Taguchi method. Six factors were varied at
      either three or two levels as follows: light intensity at three levels; three
      initial culture pHs; two species of Arthrospira; three concentrations of
      Zarrouk's medium; three rates of aeration of the culture with air mixed with 2%
      v/v carbon dioxide; and two incubation temperatures. All cultures ran for 14
      days. The optimal conditions for the production of C-PC and EPS were different.
      For both products, the best cyanobacterium proved to be Arthrospira maxima
      IFRPD1183. The production of C-PC was maximized with the following conditions: a
      light intensity of 68 umol photons m-2 s-1 (a diurnal cycle of 16-h photoperiod
      and 8-h dark period), an initial pH of 10, the full strength (100%) Zarrouk's
      culture medium, an aeration rate of 0.6 vvm (air mixed with 2% v/v CO2) and a
      culture temperature of 30  degrees C. The concentration of Zarrouk's medium was
      the most important factor influencing the final concentration of C-PC. The
      optimal conditions for maximal production of EPS were as follows: a light
      intensity of 203 umol photons m-2 s-1 with the earlier specified light-dark
      cycle; an initial pH of 9.5; a 50% strength of Zarrouk's medium; an aeration rate
      of 0.2 vvm (air mixed with 2% v/v CO2); and a temperature of 35  degrees C.
      Production of C-PC and EPS in raceway ponds is discussed.

PMID- 28497180
TI  - Performance of a capnodynamic method estimating effective pulmonary blood flow
      during transient and sustained hypercapnia.
AB  - The capnodynamic method is a minimally invasive method continuously calculating
      effective pulmonary blood flow (COEPBF), equivalent to cardiac output when intra
      pulmonary shunt flow is low. The capnodynamic equation joined with a ventilator
      pattern containing cyclic reoccurring expiratory holds, provides breath to breath
      hemodynamic monitoring in the anesthetized patient. Its performance however,
      might be affected by changes in the mixed venous content of carbon dioxide
      (CvCO2). The aim of the current study was to evaluate COEPBF during rapid
      measurable changes in mixed venous carbon dioxide partial pressure (PvCO2)
      following ischemia-reperfusion and during sustained hypercapnia in a porcine
      model. Sixteen pigs were submitted to either ischemia-reperfusion (n = 8) after
      the release of an aortic balloon inflated during 30 min or to prolonged
      hypercapnia (n = 8) induced by adding an instrumental dead space. Reference
      cardiac output (CO) was measured by an ultrasonic flow probe placed around the
      pulmonary artery trunk (COTS). Hemodynamic measurements were obtained at
      baseline, end of ischemia and during the first 5 min of reperfusion as well as
      during prolonged hypercapnia at high and low CO states. Ischemia-reperfusion
      resulted in large changes in PvCO2, hemodynamics and lactate. Bias (limits of
      agreement) was 0.7 (-0.4 to 1.8) L/min with a mean error of 28% at baseline.
      COEPBF was impaired during reperfusion but agreement was restored within 5 min.
      During prolonged hypercapnia, agreement remained good during changes in CO. The
      mean polar angle was -4.19 degrees  (-8.8 degrees  to 0.42 degrees ).
      Capnodynamic COEPBF is affected but recovers rapidly after transient large
      changes in PvCO2 and preserves good agreement and trending ability during states
      of prolonged hypercapnia at different levels of CO.

PMID- 28497179
TI  - Detectable Neuropsychological Differences in Early Preclinical Alzheimer's
      Disease: A Meta-Analysis.
AB  - The development of methods for in vivo detection of cerebral beta amyloid
      retention and tau accumulation have been increasingly useful in characterizing
      preclinical Alzheimer's disease (AD). While the association between these
      biomarkers and eventual AD has been demonstrated among cognitively intact older
      adults, the link between biomarkers and neurocognitive ability remains unclear.
      We conducted a meta-analysis to test the hypothesis that cognitively intact older
      adults would show statistically discernable differences in neuropsychological
      performance by amyloid status (amyloid negative = A-, amyloid positive = A+). We
      secondarily hypothesized a third group characterized by either CSF tau pathology
      or neurodegeneration, in addition to amyloidosis (A+/N+ or Stage 2), would show
      lower neuropsychology scores than the amyloid positive group (A+/N- or Stage 1)
      when compared to the amyloid negative group. Pubmed, PsychINFO, and other sources
      were searched for relevant articles, yielding 775 total sources. After review for
      inclusion/exclusion criteria, duplicates, and risk of bias, 61 studies were
      utilized in the final meta-analysis. Results showed A+ was associated with poorer
      performance in the domains of global cognitive function, memory, language,
      visuospatial ability, processing speed, and attention/working memory/executive
      functions when compared to A-. A+/N+ showed lower performances on memory measures
      when compared to A+/N- in secondary analyses based on a smaller subset of
      studies. Results support the notion that neuropsychological measures are
      sensitive to different stages of preclinical AD among cognitively intact older
      adults. Further research is needed to determine what constitutes meaningful
      differences in neuropsychological performance among cognitively intact older
      adults.

PMID- 28497182
TI  - The polo-like kinase 4 gene (PLK4) is overexpressed in pediatric medulloblastoma.

PMID- 28497181
TI  - New directions in fetal surgery for myelomeningocele.
AB  - The treatment of children with myelomeningocele (MMC) has improved over time,
      from supportive management to early postnatal closure to prenatal repair of the
      defect. The Management of Myelomeningocele Study (MOMS) showed that prenatal
      repair of MMC resulted in improved neurological outcomes compared to postnatal
      closure. Follow-up studies showed that prenatal repair was, as with any other
      fetal intervention, associated with higher rates of obstetrical complications.
      There was no significant difference in urological outcomes. Long-term follow-up
      of ambulatory status, executive functioning, and urological outcomes is needed to
      determine the durable effects of fetal MMC repair on mobility, functional
      independence, and the prevalence of renal insufficiency in patients with MMC who
      survive to adulthood. The future of fetal MMC repair consists of developing
      strategies to reduce maternal morbidity and improve infant outcomes. Fetoscopic
      MMC repair has been suggested as an alternative to open repair that may reduce
      obstetrical complications and the need for cesarean delivery in subsequent
      pregnancies. Translational research using mesenchymal stromal cells to augment
      fetal repair of ovine MMC has shown improvement in motor function.

PMID- 28497183
TI  - Rapid contralateral progression of focal cerebral arteriopathy distinguished from
      RNF213-related moyamoya disease and fibromuscular dysplasia.
AB  - BACKGROUND: Focal cerebral arteriopathy includes unifocal or multifocal lesions
      that are unilateral or bilateral. Large- and/or medium-sized vessels are involved
      and can be visualized on angiography. CASE REPORT: We report a case of cerebral
      infarction in a 9-year-old Japanese female who presented with a transient
      ischemic attack. Steno-occlusion involving the distal part of the internal
      carotid artery, proximal middle cerebral artery, and anterior cerebral artery was
      observed. Digital subtraction angiography demonstrated a beaded appearance in the
      cervical portion of the diseased internal carotid artery. Revascularization
      surgery was performed 45 days after the onset. A new infarction appeared on the
      other side of the anterior cerebral artery territory 7 months after the first
      onset. Antiplatelets and vasodilators were administered, and no progression was
      observed during 18 months of follow-up. Genetic analysis did not show ring finger
      protein 213 (RNF213)-related moyamoya disease, and pathological examination
      revealed no characteristics of fibromuscular dysplasia. CONCLUSION: The
      radiological and genetic features coincided with focal cerebral arteriopathy,
      which is a distinct entity from fibromuscular dysplasia and RNF213-related
      moyamoya disease.

PMID- 28497185
TI  - Reply to the Letter: "N-Butyl Cyanoacrylate Glue: The Best Hemostatic Embolic
      Agent for Patients with Acute Arterial Bleeding".

PMID- 28497184
TI  - Management of hydrocephalus in pediatric metastatic tumors of the posterior fossa
      at presentation.
AB  - PURPOSE: Presence of metastases in newly diagnosed pediatric posterior fossa
      tumors (PFT) is not a rare situation, but optimal treatment of associated
      hydrocephalus in these children has remained undetermined. METHODS: Twenty-nine
      children treated between January 2005 and December 2015 for a metastatic PFT
      associated with hydrocephalus constituted the study cohort. Patients were divided
      into three groups: ventriculoperitoneal shunt (VPS), endoscopic third
      ventriculostomy (ETV), and temporary ventricular drainage before or during tumor
      resection (PVD). RESULTS: There were 4 VPS, 18 ETV, and 7 PVD. The global
      incidence of CSF diversion failure was 52%. No case of dysfunction or
      dissemination of metastatic cells occurred in the VPS group. Recurrence of
      hydrocephalus occurred in 55% of the ETV group. Presence of multiple macroscopic
      metastases and CSF metastatic cells after tumor surgery was associated with ETV
      failure. Fifty-seven percent of the children in the PVD group were reoperated
      after an average time of 53 days. Specific oncologic treatment was initiated
      earlier in the VPS group (11 days) compared to ETV (27 days) and PVD (23 days)
      groups. CONCLUSIONS: ETV should be avoided in cases of multiple macroscopic
      metastases, and children who underwent ETV must be followed carefully when
      metastatic cells are present in CSF after tumor surgery. External ventricular
      drainage before or during surgical removal should not be considered as a final
      option to treat hydrocephalus. VPS remains a safe alternative in this situation
      and allows an early specific oncologic treatment.

PMID- 28497186
TI  - Microwave Ablation of the Lung in a Porcine Model: Vessel Diameter Predicts
      Pulmonary Artery Occlusion.
AB  - PURPOSE: To determine the size of pulmonary artery (PA) at risk for occlusion
      during percutaneous microwave ablation and to assess the effect of vessel
      diameter, number, and patency, on ablation zone volume. MATERIALS AND METHODS:
      Computed tomography (CT) fluoroscopy-guided percutaneous microwave ablations were
      performed in 8 pigs under general anesthesia. All ablations were performed at 65
      W for 5 min with a single 17-gauge antenna positioned in the central third of the
      lungs. A CT pulmonary angiogram was performed immediately after the ablations.
      The maximum diameter, number and patency of PA branches within each ablation zone
      were recorded. Ablation volumes were measured at gross dissection and with CT.
      Student's t test was used to compare ablation zone volumes among groups. RESULTS:
      Twenty-one pulmonary ablations were performed. Six of the ablation zones (29%)
      contained at least 1 occluded PA branch. The mean diameter of the occluded PA
      branches in the ablation zones (2.4 mm; range, 2.0-2.8 mm) was significantly
      smaller than non-occluded PA branches (3.7 mm; range: 2.1-6.9 mm; p = 0.009). No
      PA branches >=3 mm in size were occluded. There was no significant difference in
      volume of gross ablation zones that contained occluded versus non-occluded PAs (p
      = 0.42), one versus multiple PAs (p = 0.71), or PAs <3 mm versus >=3 mm in
      diameter (p = 0.44). CONCLUSIONS: PAs >=3 mm in size have a low risk for
      iatrogenic occlusion during percutaneous microwave ablation. The presence of
      multiple adjacent PA branches, an occluded PA branch, and a vessel diameter >=3
      mm within the ablation zone had no observed effect on ablation zone volume.

PMID- 28497187
TI  - Radiation-Induced Skin Injuries to Patients: What the Interventional Radiologist
      Needs to Know.
AB  - For a long time, radiation-induced skin injuries were only encountered in
      patients undergoing radiation therapy. In diagnostic radiology, radiation
      exposures of patients causing skin injuries were extremely rare. The introduction
      of fast multislice CT scanners and fluoroscopically guided interventions (FGI)
      changed the situation. Both methods carry the risk of excessive high doses to the
      skin of patients resulting in skin injuries. In the early nineties, several
      reports of epilation and skin injuries following CT brain perfusion studies were
      published. During the same time, several papers reported skin injuries following
      FGI, especially after percutaneous coronary interventions and neuroembolisations.
      Thus, CT and FGI are of major concern regarding radiation safety since both
      methods can apply doses to patients exceeding 5 Gy (National Council on Radiation
      Protection and Measurements threshold for substantial radiation dose level). This
      paper reviews the problem of skin injuries observed after FGI. Also, some
      practical advices are given how to effectively avoid skin injuries. In addition,
      guidelines are discussed how to deal with patients who were exposed to a
      potentially dangerous radiation skin dose during medically justified
      interventional procedures.

PMID- 28497188
TI  - Pediatric Percutaneous Osteoid Osteoma Ablation: Cone-Beam CT with Fluoroscopic
      Overlay Versus Conventional CT Guidance.
AB  - PURPOSE: To compare technical success, clinical success, complications, radiation
      dose, and total room utilization time for osteoid osteoma thermal (radiofrequency
      or microwave) ablation using cone-beam computed tomography (CBCT) with two-axis
      fluoroscopic navigational overlay versus conventional computed tomography (CT)
      guidance. MATERIALS AND METHODS: A retrospective review was performed to identify
      all osteoid osteoma ablations performed over a 5.5-year period at a single
      tertiary care pediatric hospital. Twenty-five ablations (15 radiofrequency and 10
      microwave) in 23 patients undergoing fluoroscopic CBCT-guided osteoid osteoma
      ablation were compared to 35 ablations (35 radiofrequency) in 32 patients
      undergoing ablation via conventional CT guidance. Dose area product and dose
      length product were recorded for CBCT and conventional CT, respectively, and
      converted to effective doses. Technical success, clinical success (cessation of
      pain and medication use 1 month after ablation), complications, radiation dose,
      and total room utilization time were compared. RESULTS: All procedures were
      technically successful. Twenty-two of 25 (88.0%) CBCT and 31 of 35 (88.6%)
      conventional CT-guided ablations achieved immediate clinical success. There were
      two minor complications in each group and no major complications. Mean effective
      radiation dose was significantly lower for CBCT compared to CT guidance (0.12 vs.
      0.39 mSv, p = 0.02). Mean total room utilization time for CBCT was longer (133.5
      vs. 97.5 min, p = 0.0001). CONCLUSIONS: Fluoroscopic CBCT guidance for
      percutaneous osteoid osteoma ablation yields similar technical and clinical
      success, reduced radiation dose, and increased total room utilization time
      compared to conventional CT guidance.

PMID- 28497189
TI  - Quantification of mitral regurgitation during percutaneous mitral valve repair:
      added value of simultaneous hemodynamic and 3D echocardiographic assessment.
AB  - The objective of this study was to investigate the usefulness of intraprocedural
      hemodynamic monitoring for MR evaluation during pMRV. Assessment of mitral
      regurgitation (MR) during percutaneous mitral valve repair (pMVR) procedure is
      challenging. 3D color Doppler allows exact quantification of MR, but is
      technically demanding. Sixty patients with moderate to severe MR (14 with
      structural and 46 functional MR) were included in the study. Intraprocedural
      pressure curves were continuously obtained in the left atrium (LA) and left
      ventricle (LV). Transesophageal echocardiography was performed using 3D color
      Doppler derived mean vena contracta area (VCAmean) and mitral regurgitation
      volume (RegVol) to quantify MR severity before and after each clip implantation.
      In the entire patient group, strongest correlations were observed firstly between
      VCA and the raise of the ascending limb of the left atrial V pressure wave
      (Vascend; r = 0.58, p < 0.001) and secondly between the difference of peak V wave
      pressure and mean LA pressure divided by systolic LV pressure [(Vpeak - LAmean) -
      LVsystole; r = 0.53, p < 0.001]. In patients with structural MR, the highest area
      under the ROC curve for prediction of mild MR (VCAmean < 0.2 cm2 and RegVol < 30
      ml) after clip implantation was found for Vascend (AUC 0.89, p < 0.001) whereas
      in functional MR calculation of (Vpeak - LAmean) - LVsystole showed the highest
      predictive value (AUC 0.69, p = 0.003). Invasive pressure monitoring can give a
      direct feedback with regard to the success of clip placement during pMVR.

PMID- 28497190
TI  - Abstracts of the ECTS congress 2017.

PMID- 28497191
TI  - Evaluation of the coronary circulation and calcification in children on regular
      hemodialysis.
AB  - BACKGROUND: The objective of this study was to evaluate the coronary circulation
      and calcification in children with end-stage renal disease (ESRD) on
      hemodialysis. METHODS: A total of 50 children with ESRD and 50 healthy controls
      were enrolled in the study. Cardiac functions and coronary blood flow were
      evaluated with conventional and tissue Doppler echocardiography. Coronary artery
      calcification (CAC) was evaluated using high-resolution multidetector computed
      tomography (CT). RESULTS: The hyperemic coronary flow volume (CFV) and coronary
      flow reserve were significantly lower in the patient group than in the controls,
      while there was no significant difference in the baseline CFV between the two
      groups. Hypertension was present in 60% and CAC was observed in 20% of the
      children in the patient group. CAC was present in 30% of the children in the
      hypertensive subgroup. The left ventricle myocardial performance index (LV MPI),
      CAC score, duration of hypertension and level of diastolic blood pressure were
      independent predictors of the coronary blood flow, and LV MPI, serum parathyroid
      hormone, duration of dialysis and E'/A' mitral valve were independent predictors
      of coronary calcification. CONCLUSION: High diastolic blood pressure, long
      duration of hypertension, high LV MPI and increased CAC scores are independent
      risk factors for impaired coronary blood flow in children with ESRD.

PMID- 28497192
TI  - Redox changes of ferredoxin, P700, and plastocyanin measured simultaneously in
      intact leaves.
AB  - Properties and performance of the recently introduced Dual/KLAS-NIR
      spectrophotometer for simultaneous measurements of ferredoxin (Fd), P700, and
      plastocyanin (PC) redox changes, together with whole leaf chlorophyll a (Chl)
      fluorescence (emission >760, 540 nm excitation) are outlined. Spectral
      information on in vivo Fd, P700, and PC in the near-infrared region (NIR, 780
      1000 nm) is presented, on which the new approach is based. Examples of
      application focus on dark-light and light-dark transitions, where maximal redox
      changes of Fd occur. After dark-adaptation, Fd reduction induced by moderate
      light parallels the Kautsky effect of Chl fluorescence induction. Both signals
      are affected analogously by removal of O2. A rapid type of Fd reoxidation,
      observed after a short pulse of light before light activation of linear electron
      transport (LET), is more pronounced in C4 compared to C3 leaves and interpreted
      to reflect cyclic PS I (CET). Light activation of LET, as assessed via the rate
      of Fd reoxidation after short light pulses, occurs at very low intensities and is
      slowly reversed (half-time ca. 20 min). Illumination with strong far-red light
      (FR, 740 nm) reveals two fractions of PS I, PS I (LET), and PS I (CET), differing
      in the rates of Fd reoxidation upon FR-off and the apparent equilibrium constants
      between P700 and PC. Parallel information on oxidation of Fd and reduction of
      P700 plus PC proves essential for identification of CET. Comparison of maize (C4)
      with sunflower and ivy (C3) responses leads to the conclusion that segregation of
      two types of PS I may not only exist in C4 (mesophyll and bundle sheath cells),
      but also in C3 photosynthesis (grana margins plus end membranes and stroma
      lamellae).

PMID- 28497193
TI  - Evaluation of new Cu(II) complexes as a novel class of inhibitors against plant
      carbonic anhydrase, glutathione reductase, and photosynthetic activity in
      photosystem II.
AB  - Increasing inefficiency of production of important agricultural plants raises one
      of the biggest problems in the modern world. Herbicide application is still the
      best method of weed management. Traditional herbicides blocking only one of the
      plant metabolic pathways is ineffective due to the rapid growth of herbicide
      resistant weeds. The synthesis of novel compounds effectively suppressing several
      metabolic processes, and therefore achieving the synergism effect would serve as
      the alternative approach to weed problem. For this reason, recently, we
      synthesized a series of nine novel Cu(II) complexes and four ligands,
      characterized them with different analyses techniques, and carried out their
      primary evaluation as inhibitors of photosynthetic electron transfer in spinach
      thylakoids (design, synthesis, and evaluation of a series of Cu(II) based metal
      organic complexes as possible inhibitors of photosynthesis, J Photochem Photobiol
      B, submitted). Here, we evaluated in vitro inhibitory potency of these agents
      against: photochemistry and carbonic anhydrase activity of photosystem II (PSII);
      alpha-carbonic anhydrase from bovine erythrocytes; as well as glutathione
      reductase from chloroplast and baker's yeast. Our results show that all Cu(II)
      complexes excellently inhibit glutathione reductase and PSII carbonic anhydrase
      activity. Some of them also decently inhibit PSII photosynthetic activity.

PMID- 28497194
TI  - Treatment and outcomes of recurrent hepatocellular carcinomas.
AB  - PURPOSE: Surgery is one of the best options for curative treatment of
      hepatocellular carcinomas (HCC). Recurrences are nevertheless common (45-75%).
      This study aimed to compare overall survival (OS) of patients with recurrent HCC
      after primary resection to OS of patients without recurrence. METHODS: A
      retrospective review of all HCC patients operated between 1993 and 2015 was
      performed. Median and 5-year OS were calculated. RESULTS: This study included 147
      HCC patients. Sixty-seven patients presented a recurrence (46%). Patients with
      recurrence had a worse prognosis than those without recurrence (median OS 63 vs.
      82 months, 5-year OS 47 vs. 54%, p = 0.036). First-line performed treatments were
      radiofrequency ablation (18, RFA), chemo-embolization (16, TACE), repeat
      hepatectomy (10), systemic chemotherapy (4), radio-embolization (1), and
      alcoholization (1). Palliative care was performed in 17 patients. Median OS of
      patients treated by RFA, TACE, or repeat hepatectomy were similar (77, 71, and 84
      months, p = 0.735). Patients treated with chemotherapy/palliative care had lower
      median OS compared to interventional treatments (20 vs. 77 months, p < 0.0001).
      CONCLUSIONS: Recurrence after surgical HCC resection is frequent and negatively
      impacts OS. Interventional treatments of recurrences offered improved outcomes
      compared to medical care. In selected patients, RFA, TACE, and repeat hepatectomy
      allowed similar OS as non-recurrent cases.

PMID- 28497195
TI  - Olfaction in a viscous environment: the "color" of sexual smells in Temora
      longicornis.
AB  - We investigate chemical aspects of mating in the marine copepod Temora
      longicornis (Copepoda, Calanoidea). Our emphasis is the female pheromone
      signaling in form of well-defined trails for males to follow, observed in Doall
      et al. (Phil Trans R Soc Lond B 353:681-689, 1998). The viscous environment and
      the properties of the odorants play important roles as the spread of the
      pheromone trail limits the time during which it is useful for tracing. A key
      observation from our earlier work is the ability of a searching male to detect
      the direction of the female and to correct its swimming direction if necessary.
      We propose a simple mathematical model for the spread of a pheromone from a
      moving source and carry out numerical simulations of two possible detection
      mechanisms. We find that a searching agent that is capable to detect a ratio
      outperforms a searcher that depends on the gradient of a single compound. This
      suggests that copepod sex pheromones consist of blends of chemical compounds, and
      that a ratio detection mechanism similar to that in airborne insects is at work.

PMID- 28497196
TI  - An objective view of biological diversity: how history and epistemology shaped
      current treatment.
AB  - The concept of biological diversity has inspired important discussions throughout
      the history of ecology. Although its meaning and usefulness have been questioned,
      it is currently one of the key artifacts of ecology. One way to try to understand
      why such a concept has undergone so many discussions is to examine its emergence
      and history from the epistemology perspective. In the present work, we
      investigated how the emergence of mechanical objectivity (as an epistemic virtue)
      and trained judgment affected how ecologists address the concept of biological
      diversity. Thus, we employed the theoretical framework of objectivity (provided
      by Daston and Galison in Objectivity. Zone Books, New York, 2007) to analyze
      different periods of scientific literature in ecology ("initial period": end of
      the nineteenth century and beginning of the twentieth century; "intermediate
      period": mid-twentieth century; "contemporary period": from the second half of
      the 1980s). Our results showed that the emergence of mechanical objectivity and
      trained judgment affected biological diversity research. In particular, the ideal
      of objectivity behind the way in which the concept of biological diversity is
      addressed in different fields of contemporary ecology could not be the same.

PMID- 28497197
TI  - Erratum to: Management of Recurrent Retroperitoneal Sarcoma (RPS) in the Adult: A
      Consensus Approach from the Trans-Atlantic RPS Working Group.

PMID- 28497198
TI  - Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with
      recurrent prostate cancer: evaluation in 1007 patients.
AB  - PURPOSE: Since the clinical introduction of 68Ga-PSMA-11 PET/CT, this imaging
      method has rapidly spread and is now regarded as a significant step forward in
      the diagnosis of recurrent prostate cancer (PCa). The aim of this study was to
      analyse the influence of several variables with possible influence on PSMA ligand
      uptake in a large cohort. METHODS: We performed a retrospective analysis of 1007
      consecutive patients who were scanned with 68Ga-PSMA-11 PET/CT (1 h after
      injection) from January 2014 to January 2017 to detect recurrent disease.
      Patients with untreated primary PCa or patients referred for PSMA radioligand
      therapy were excluded. The possible effects of different variables including PSA
      level and PSA doubling time (PSADT), PSA velocity (PSAVel), Gleason score (GSC,
      including separate analysis of GSC 7a and 7b), ongoing androgen deprivation
      therapy (ADT), patient age and amount of injected activity were evaluated.
      RESULTS: In 79.5% of patients at least one lesion with characteristics suggestive
      of recurrent PCa was detected. A pathological (positive) PET/CT scan was
      associated with PSA level and ADT. GSC, amount of injected activity, patient age,
      PSADT and PSAVel were not associated with a positive PET/CT scan in multivariate
      analysis. CONCLUSION: 68Ga-PSMA-11 PET/CT detects tumour lesions in a high
      percentage of patients with recurrent PCa. Tumour detection is clearly associated
      with PSA level and ADT. Only a tendency for an association without statistical
      significance was found between higher GSC and a higher probability of a
      pathological PET/CT scan. No associations were found between a pathological 68Ga
      PSMA-11 PET/CT scan and patient age, amount of injected activity, PSADT or
      PSAVel.

PMID- 28497199
TI  - Arachidonic Acid Induces ARE/Nrf2-Dependent Heme Oxygenase-1 Transcription in Rat
      Brain Astrocytes.
AB  - Arachidonic acid (AA) is a major product of phospholipid hydrolysis catalyzed by
      phospholipase A2 during neurodegenerative diseases. AA exerts as a second
      messenger to regulate various signaling components which may be involved in
      different pathophysiological processes. Astrocytes are the main types of CNS
      resident cells which maintain and support the physiological function of brain. AA
      has been shown to induce ROS generation through activation of NADPH oxidases
      (Noxs) which may play a key role in the expression of heme oxygenase-1 (HO-1).
      Therefore, this study was designed to investigate the mechanisms underlying AA
      induced HO-1 expression in rat brain astrocytes (RBA-1). We found that AA induced
      HO-1 protein and mRNA expression and promoter activity in RBA-1, which was
      mediated through the synthesis of 15-deoxy-Delta12,14-prostaglandin D2-activated
      peroxisome proliferator-activated receptor-gamma (PPARgamma) receptors. This note
      was confirmed by transfection with PPARgamma small interfering RNAs (siRNA) which
      attenuated the AA-mediated responses. AA-induced HO-1 expression was mediated
      through Nox/ROS generation, which was inhibited by Nox inhibitors
      (diphenyleneiodonium and apocynin) and ROS scavengers (N-acetyl cysteine).
      Moreover, AA-induced HO-1 expression was mediated through phosphorylation of Src,
      Pyk2, platelet-derived growth factor, PI3K/Akt, and ERK1/2 which were inhibited
      by the pharmacological inhibitors including PP1, PF431396, AG1296, LY294002, and
      U0126 or by transfection with respective siRNAs. AA-enhanced Nrf2 expression and
      HO-1 promoter activity was inhibited by transfection with Nrf2 siRNA or by these
      pharmacological inhibitors. Furthermore, chromatin immunoprecipitation assay
      confirmed that Nrf2 and PPARgamma were associated with the proximal antioxidant
      response element (ARE)-binding site on HO-1 promoter, suggesting that
      Nrf2/PPARgamma are key transcription factors modulating HO-1 expression. AA
      induced ARE promoter activity was also reduced by these pharmacological
      inhibitors. These findings suggested that AA increases formation of Nrf2 and
      PPARgamma complex and binding with ARE1 binding site through Src, Pyk2, PI3K/Akt,
      and ERK1/2, which further induced HO-1 expression in RBA-1 cells.

PMID- 28497200
TI  - Effect of Lipoic Acid on the Biochemical Mechanisms of Resistance to Bortezomib
      in SH-SY5Y Neuroblastoma Cells.
AB  - Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in
      infancy. Despite the standard treatment for NB is based on the combination of
      chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and
      cisplatin, chemoresistance occurs over the time. The aim of the present research
      was to evaluate the effect of bortezomib (BTZ) (50 nM) on NB cell viability and
      how lipoic acid (ALA) (100 MUM) modifies pharmacological response to this
      chemotherapeutic agent. Cell viability was assessed by ATP luminescence assay
      whereas expression of oxidative stress marker (i.e., heme oxygenase-1) and
      endoplasmic reticulum stress proteins was performed by real-time PCR, western
      blot, and immunofluorescence. Our data showed that BTZ treatment significantly
      reduced cell viability when compared to untreated cultures (about 40%).
      Interestingly, ALA significantly reduced the efficacy of BTZ (about 30%).
      Furthermore, BTZ significantly induced heme oxygenase-1 as a result of increased
      oxidative stress and such overexpression was prevented by concomitant treatment
      with ALA. Similarly, ALA significantly reduced BTZ-mediated endoplasmic reticulum
      stress as measured by reduction in BiP1 and IRE1alpha, ERO1alpha, and PDI
      expression. In conclusion, our data suggest that BTZ efficacy is dependent on
      cellular redox status and such mechanisms may be responsible of chemoresistance
      to this chemotherapeutic agent.

PMID- 28497203
TI  - Retraction Note to: The Clinical Implications of Human Telomerase Reverse
      Transcriptase Expression in Grade and Prognosis of Gliomas: a Systematic Review
      and Meta-analysis.

PMID- 28497201
TI  - Huntington Disease as a Neurodevelopmental Disorder and Early Signs of the
      Disease in Stem Cells.
AB  - Huntington disease (HD) is a dominantly inherited disorder caused by a CAG
      expansion mutation in the huntingtin (HTT) gene, which results in the HTT protein
      that contains an expanded polyglutamine tract. The adult form of HD exhibits a
      late onset of the fully symptomatic phase. However, there is also a long
      presymptomatic phase, which has been increasingly investigated and recognized as
      important for the disease development. Moreover, the juvenile form of HD, evoked
      by a higher number of CAG repeats, resembles a neurodevelopmental disorder and
      has recently been the focus of additional interest. Multiple lines of data, such
      as the developmental necessity of HTT, its role in the cell cycle and
      neurogenesis, and findings from pluripotent stem cells, suggest the existence of
      a neurodevelopmental component in HD pathogenesis. Therefore, we discuss the
      early molecular pathogenesis of HD in pluripotent and neural stem cells, with
      respect to the neurodevelopmental aspects of HD.

PMID- 28497204
TI  - The biology and the importance of Photobacterium species.
AB  - Photobacterium species are Gram-negative coccobacilli which are distributed in
      marine habitats worldwide. Some species are unique because of their capability to
      produce luminescence. Taxonomically, about 23 species and 2 subspecies are
      validated to date. Genomes from a few Photobacterium spp. have been sequenced and
      studied. They are considered a special group of bacteria because some species are
      capable of producing essential polyunsaturated fatty acids, antibacterial
      compounds, lipases, esterases and asparaginases. They are also used as biosensors
      in food and environmental monitoring and detectors of drown victim, as well as an
      important symbiont.

PMID- 28497205
TI  - Transmission electron microscopy artifacts in characterization of the
      nanomaterial-cell interactions.
AB  - We investigated transmission electron microscopy artifacts obtained using
      standard sample preparation protocols applied to the investigation of Escherichia
      coli cells exposed to common nanomaterials, such as TiO2, Ag, ZnO, and MgO. While
      the common protocols for some nanomaterials result only in known issues of
      nanomaterial-independent generation of anomalous deposits due to fixation and
      staining, for others, there are reactions between the nanomaterial and chemicals
      used for post-fixation or staining. Only in the case of TiO2 do we observe only
      the known issues of nanomaterial-independent generation of anomalous deposits due
      to exceptional chemical stability of this material. For the other three
      nanomaterials, different artifacts are observed. For each of those, we identify
      causes of the observed problems and suggest alternative sample preparation
      protocols to avoid artifacts arising from the sample preparation, which is
      essential for correct interpretation of the obtained images and drawing correct
      conclusions on cell-nanomaterial interactions. Finally, we propose modified
      sample preparation and characterization protocols for comprehensive and
      conclusive investigations of nanomaterial-cell interactions using electron
      microscopy and for obtaining clear and unambiguous revelation whether the
      nanomaterials studied penetrate the cells or accumulate at the cell membranes. In
      only the case of MgO and ZnO, the unambiguous presence of Zn and Mg could be
      observed inside the cells.

PMID- 28497206
TI  - [Current status of teaching in lung ultrasound : Query of knowledge, utilization,
      need, and preferred teaching method].
AB  - BACKGROUND: Lung ultrasound (LUS) is a point-of-care technique which can quickly
      identify or rule out pathological findings. To date, it is unclear if knowledge
      about the use of LUS is readily available. OBJECTIVES: We aimed to identify how
      much knowledge about the use of LUS is present, if there is a need for teaching
      in LUS, as well as the preferred teaching method in LUS. MATERIALS AND METHODS: A
      total of 54 participants from two university departments of anesthesiology were
      randomized into the groups Online, Classroom, and Control. The Online group was
      taught by videos, the Classroom group by a traditional lecture with hands-on
      training, and the Control group was not taught at all. We conducted a pre- and
      posttest as well as a retention test 4 weeks after the end of the study by means
      of a survey (comparison with Mann-Whitney U test or t-test, respectively, with p
      < 0.05 considered to be significant). RESULTS: LUS is used "rarely" or "never",
      and mainly if there is a suspicion for pleural effusion (41.3%). There is a need
      for LUS (Online: 21.7%; Classroom: 60.9%; Control: 62.5%, p < 0.05). Hybrid
      teaching consisting of classroom-based and online-based teaching is preferred by
      the users (Online: 52.2%; Classroom: 56.5%; Control: 62.5%). At the end of the
      study, 32.6% of the participants of the intervention groups had used LUS in the
      diagnosis of a pneumothorax. Of the participants, 93.5% planned to use LUS more
      often in the future. CONCLUSIONS: LUS is rarely used. There is a considerable
      need for teaching of LUS. Internet-based teaching and traditional lectures are
      considered equal. Both teaching methods improve the knowledge about LUS and lead
      to increased use of LUS in daily practice. The participants prefer hybrid
      teaching incorporating both teaching methods.

PMID- 28497207
TI  - Evaluation of rumen-protected choline additive to diet on productive performance
      of male Zaraibi growing goats during hot summer season in Egypt.
AB  - Twenty Zaraibi goat bucks were used in this experiment which lasted 3 months
      during summer season of Egypt. The animals were divided randomly into two equal
      groups. The first group was kept without treatment as control while in the second
      group, rumen-protected choline (RPC) at the level of 20 g/buck/day was added to
      the concentrate feed mixture at the morning feeding. RPC additives to diet of
      Zaraibi goat bucks during the period of hot summer season increased (P < 0.01)
      total gain and average daily gain compared to the control group. RPC increased (P
      < 0.05) dry matter intake and feed conversion while water intake was not affected
      by RPC additives. RPC increased (P < 0.05) red and white blood cell (RBC * 106,
      WBC * 103) counts and hemoglobin concentration and hematocrit percentage. RPC
      increased total protein (P < 0.05), globulin, and gamma-globulin (P < 0.01). On
      the other hand, total lipids, total cholesterol, and triglyceride concentrations
      decreased (P < 0.05 and P < 0.05) while phospholipids, glucose, and choline
      concentrations increased (P < 0.01) due to RPC supplementation. RPC increased (P
      < 0.01) thyroxin and triiodothyronine, increased (P < 0.05) testosterone levels,
      and decreased (P < 0.01) cortisol level compared with control bucks. It is
      concluded that dietary RPC at the rate of 20 g daily is required for growing male
      goats, especially, under heat stress conditions of summer season in Egypt and
      showed the best results concerning the growth, feed conversion, blood
      metabolites, and economic efficiency.

PMID- 28497202
TI  - Exosomes and their Application in Biomedical Field: Difficulties and Advantages.
AB  - The science of gene therapy has experienced a controversial history. At first,
      the initial concept that various disorders become curable by gene transferring
      was very exciting and challengeable. However, the problems and difficulties
      related to emerging techniques and unwanted side effects seen in some patients
      who have undergone gene therapy make some questions against the safety of novel
      molecular medicine approach. In line with this statement, discovery and
      developing a good bio-vector possessing low toxicity and high efficiency rate are
      the most important issues in gene therapy field. Introducing exosomes as vectors
      for gene delivery gives us a new opportunity in gene-based therapy. Exosomes,
      ranging from 30 to 120 nm in diameter, have unique lipid and protein composition.
      These nanostructures participate in cell-to-cell cross-talk, regulation of immune
      system, and the transport of genetic material. Besides the inherent potency of
      exosomes in gene therapy, a better understanding of their biology,
      characteristics, production, targeting, and cargo loading still need to be
      elucidated. In the current review, we exclusively focused on the various facets
      of exosomes and their importance as a bio-shuttle in gene therapy.

PMID- 28497208
TI  - The Detrimental Effects of Adolescents' Chronic Loneliness on Motivation and
      Emotion Regulation in Social Situations.
AB  - In adolescence, when establishing and maintaining satisfying social relationships
      is a key developmental task, chronic loneliness is related to a host of negative
      outcomes. This study aimed at examining motivational and regulatory factors
      related to chronic loneliness. Specifically, this study investigated chronically
      lonely adolescents' responses to hypothetical vignettes of social inclusion and
      exclusion, thereby focusing on (a) adolescents' willingness and motivation to
      approach social inclusion and (b) emotion regulation strategies to deal with
      social exclusion. A total of 730 adolescents (Mage = 15.43 years, 72% female)
      participated in this four-wave study with annual loneliness assessments and
      hypothetical vignettes of social inclusion and exclusion at the final wave. After
      each social inclusion vignette, participants rated their willingness to accept
      the invitation for social inclusion and five types of motivation to approach the
      situation. After each social exclusion vignette, participants rated nine
      cognitive emotion regulation strategies. Compared to individuals following other
      trajectories, chronically lonely adolescents were less likely to accept
      invitations for social inclusion and the quality of their motivation for
      accepting such invitations was lower. Further, they were more likely to employ
      maladaptive emotion regulation strategies. In sum, this study adds significantly
      to understanding the motivational and regulatory processes that differentiate
      chronically lonely adolescents from adolescents following other trajectories.

PMID- 28497209
TI  - Pharmacists' perspectives of the current status of pediatric asthma management in
      the U.S. community pharmacy setting.
AB  - Objective To explore community pharmacists' continuing education, counseling and
      communication practices, attitudes and barriers in relation to pediatric asthma
      management. Setting Community pharmacies in Michigan, United States. Methods
      Between July and September 2015 a convenience sample of community pharmacists was
      recruited from southeastern Michigan and asked to complete a structured, self
      reported questionnaire. The questionnaire elucidated information on 4 general
      domains relating to pharmacists' pediatric asthma management including: (1)
      guidelines and continuing education (CE); (2) counseling and medicines; (3)
      communication and self-management practices; (4) attitudes and barriers to
      practice. Regression analyses were conducted to determine predictors towards
      pharmacists' confidence/frequency of use of communication/counseling strategies.
      Main outcome measure Confidence in counseling skills around asthma. Results 105
      pharmacists completed the study questionnaire. Fifty-four percent of pharmacists
      reported participating in asthma related CE in the past year. Over 70% of
      pharmacists reported confidence in general communication skills, while a lower
      portion reported confidence in engaging in higher order self-management
      activities that involved tailoring the regimen (58%), decision-making (50%) and
      setting short-term (47%) and long-term goals (47%) with the patient and caregiver
      for managing asthma at home. Pharmacists who reported greater use of recommended
      communication/self-management strategies were more likely to report confidence in
      implementing these communication/self-management strategies when counseling
      caregivers and children with asthma [Beta (B) Estimate 0.58 SE (0.08), p <
      0.001]. Female pharmacists [B Estimate -2.23 SE (1.01), p < 0.05] and those who
      reported beliefs around doctors being the sole provider of asthma education [B
      Estimate -1.00 SE (0.32), p < 0.01] were less likely to report confidence in
      implementing communication/self-management strategies. Conclusion A pharmacists'
      confidence may influence their ability to implement recommended self-management
      counseling strategies. This study showed that community pharmacists are confident
      in general communication. However pharmacists are reporting lower confidence
      levels in counseling on higher order self-management strategies with patients.
      More appropriate and targeted continuing education programs for pharmacists
      around asthma self-management education are recommended.

PMID- 28497210
TI  - Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from
      Mumbai.
AB  - Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009
      which subsequently became endemic in many parts of the country. Influenza A
      viruses have the ability to evade the immune response through its ability of
      antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09
      viruses circulating in Mumbai during the pandemic and post-pandemic period.
      Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were
      inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular
      and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to
      understand the evolution and genetic diversity of the strains. Nucleotide and
      amino acid sequences of the HA gene of Mumbai isolates when compared to
      A/California/07/2009-vaccine strain revealed 14 specific amino acid differences
      located at the antigenic sites. Amino acid variations in HA and NA gene resulted
      in changes in the N-linked glycosylation motif which may lead to immune evasion.
      Phylogenetic analysis of the isolates revealed their evolutionary position with
      vaccine strain A/California/07/2009 but had undergone changes gradually. The
      findings in the present study confirm genetic variability of influenza viruses
      and highlight the importance of continuous surveillance during influenza
      outbreaks.

PMID- 28497211
TI  - Association of toll-like receptor gene polymorphisms and its interaction with HPV
      infection in determining the susceptibility of cervical cancer in Chinese Han
      population.
AB  - The aim of the study is to investigate the association of several single
      nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and
      additional gene-gene and gene-human papillomavirus (HPV) infection interaction
      with cervical cancer risk. A total of 1262 participants are selected, including
      420 cervical cancer patients and 842 control participants. Generalized
      multifactor dimensionality reduction (GMDR) was used to screen the best
      interaction combination among five SNPs within TLR gene and HPV infection.
      Logistic regression was performed to calculate the ORs (95 %CI) for association
      of five SNPs within TLR gene and additional gene-HPV infection interaction with
      cervical cancer risk. Cervical cancer risk was significantly higher in carriers
      of the T allele of rs3775290 within TLR2 gene, the G allele of rs7873784 within
      TLR4 gene, and the A allele of rs352140 within TLR9 gene than those with wild
      genotype; adjusted ORs (95 %CI) were 1.78 (1.20-2.24), 1.65 (1.23-2.12), and 1.70
      (1.16-2.31). However, we did not find any significant association of rs4986791
      and rs11536889 with cervical cancer risk. GMDR analysis suggested a significant
      two-locus model (p = 0.0107) involving rs352140 and HPV infection. Subjects with
      HPV infection and rs352140-GA + AA genotype within TLR9 gene have the highest
      cervical cancer risk, compared to no HPV infection participants with rs352140-GG
      genotype, OR (95 %CI) = 3.22 (1.68-4.81). Pairwise LD analysis did not find any
      significant haplotype combination associated with cervical cancer risk. The minor
      alleles of TLR2-rs3775290, TLR4-rs7873784, and TLR9-rs352140, and interaction
      between rs352140 and HPV infection were all associated with increased cervical
      cancer risk.

PMID- 28497212
TI  - Renal Osteodystrophy or Kidney-Induced Osteoporosis?
AB  - PURPOSE OF REVIEW: Chronic kidney disease (CKD) affects nearly 10% of the
      population. The incidence of fractures in population studies demonstrate an
      increase with worsening stages of kidney disease suggesting specific CKD related
      causes of fracture. RECENT FINDINGS: The increase in fractures with CKD most
      likely represents disordered bone quality due to the abnormal bone remodeling
      from renal osteodystrophy. There is also an increase in fractures with age in
      patients with CKD, suggesting that patients with CKD also have many fracture risk
      factors common to patients without known CKD. Osteoporosis is defined by the
      National Institutes of Health as "A skeletal disorder characterized by
      compromised bone strength predisposing to an increased risk of fracture. Bone
      strength reflects the integration of two main features: bone quantity and bone
      quality." Thus, CKD-related fractures can be considered a type of osteoporosis
      where the bone quality is additionally impaired above that of age/hormonal
      related osteoporosis. Perhaps using the term CKD-induced osteoporosis, similar to
      steroid-induced osteoporosis, will allow patients with CKD to be studied in
      trials investigating therapeutic agents. In this series, we will examine how CKD
      induced osteoporosis may be diagnosed and treated.

PMID- 28497214
TI  - Comparative theoretical studies of differently bridged nitramino-substituted
      ditetrazole 2-N-oxides with high detonation performance and an oxygen balance of
      around zero.
AB  - In this work, six (A-F) nitramino (-NHNO2)-substituted ditetrazole 2-N-oxides
      with different bridging groups (-CH2-, -CH2-CH2-, -NH-, -N=N-, and -NH-NH-) were
      designed. The six compounds were based on the parent compound tetrazole 2-N
      oxide, which possesses a high oxygen balance and high density. The structure,
      heat of formation, density, detonation properties (detonation velocity D and
      detonation pressure P), and the sensitivity of each compound was investigated
      systematically via density functional theory, by studying the electrostatic
      potential, and using molecular mechanics. The results showed that compounds A-F
      all have outstanding energetic properties (D: 9.1-10.0 km/s; P: 38.0-46.7 GPa)
      and acceptable sensitivities (h 50: 28-37 cm). The bridging group present was
      found to greatly affect the detonation performance of each ditetrazole 2-N-oxide,
      and the compound with the -NH-NH- bridging group yielded the best results.
      Indeed, this compound (F) was calculated to have comparable sensitivity to the
      famous and widely used high explosive 1,3,5,7-tetranitro-1,3,5,7-tetrazocane
      (HMX), but with values of D and P that were about 8.7% and 19.4% higher than
      those for HMX, respectively. The present study shows that tetrazole 2-N-oxide is
      a useful parent compound which could potentially be used in the design of new and
      improved high-energy compounds to replace existing energetic compounds such as
      HMX.

PMID- 28497213
TI  - Bone Pain and Muscle Weakness in Cancer Patients.
AB  - PURPOSE OF REVIEW: In this article, we will discuss the current understanding of
      bone pain and muscle weakness in cancer patients. We will describe the underlying
      physiology and mechanisms of cancer-induced bone pain (CIBP) and cancer-induced
      muscle wasting (CIMW), as well as current methods of diagnosis and treatment. We
      will discuss future therapies and research directions to help patients with these
      problems. RECENT FINDINGS: There are several pharmacologic therapies that are
      currently in preclinical and clinical testing that appear to be promising
      adjuncts to current CIBP and CIMW therapies. Such therapies include
      resiniferitoxin, which is a targeted inhibitor of noceciptive nerve fibers, and
      selective androgen receptor modulators, which show promise in increasing lean
      mass. CIBP and CIMW are significant causes of morbidity in affected patients.
      Current management is mostly palliative; however, targeted therapies are poised
      to revolutionize how these problems are treated.

PMID- 28497216
TI  - Genome characterization of sweet potato symptomless virus 1: a mastrevirus with
      an unusual nonanucleotide sequence.
AB  - Complete genomic sequences of nine isolates of sweet potato symptomless virus 1
      (SPSMV-1), a virus of the genus Mastrevirus in the family Geminiviridae, were
      determined from sweet potato accessions from different countries and found to be
      2,559-2,602 nucleotides in length. These isolates shared 97-100% genome sequence
      identity and had an unusual nonanucleotide sequence (TAAGATTCC) in a large
      intergenic region as well as an additional open reading frame, C3, which is
      conserved in dicot-infecting mastreviruses.

PMID- 28497215
TI  - Evidence-based prevention and treatment of osteoporosis after spinal cord injury:
      a systematic review.
AB  - PURPOSE: Spinal cord injury (SCI) results in accelerated bone mineral density
      (BMD) loss and disorganization of trabecular bone architecture. The mechanisms
      underlying post-SCI osteoporosis are complex and different from other types of
      osteoporosis. Findings of studies investigating efficacy of pharmacological or
      rehabilitative interventions in SCI-related osteoporosis are controversial. The
      aim of this study was to review the literature pertaining to prevention and
      evidence-based treatments of SCI-related osteoporosis. METHODS: In this
      systematic review, MEDLINE, EMBASE, PubMed, and the Cochrane Library were used to
      identify papers from 1946 to December 31, 2015. The search strategy involved the
      following keywords: spinal cord injury, osteoporosis, and bone loss. RESULTS:
      Finally, 56 studies were included according to the inclusion criteria. Only 16
      randomized controlled trials (involving 368 patients) were found. We found
      following evidences for effectiveness of bisphosphonates in prevention of BMD
      loss in acute SCI: very low-quality evidence for clodronate and etidronate, low
      quality evidence for alendronate, and moderate-quality evidence for zoledronic
      acid. Low-quality evidence showed no effectiveness for tiludronate. In chronic
      SCI cases, we found low-quality evidence for effectiveness of vitamin D3 analogs
      combined with 1-alpha vitamin D2. However, low-quality inconsistent evidence
      exists for alendronate. For non-pharmacologic interventions, very low-quality
      evidence exists for effectiveness of standing with or without treadmill walking
      in acute SCI. Other low-quality evidences indicated that electrical stimulation,
      tilt-table standing, and ultrasound provide no significant effects. Very low
      quality evidence did not show any benefit for low-intensity (3 days per week)
      cycling with functional electrical stimulator in chronic SCI. CONCLUSIONS: No
      recommendations can be made from this review, regarding overall low quality of
      evidence as a result of high risk of bias, low sample size in most of the
      studies, and notable heterogeneity in type of intervention, outcome measurement,
      and duration of treatment. Therefore, future high-quality RCT studies with higher
      sample sizes and more homogeneity are strongly recommended to provide high
      quality evidence and make applicable recommendations for prevention and treatment
      of SCI-related bone loss.

PMID- 28497217
TI  - Inhibition of Clostridium difficile in Mice Using a Mixture of Potential
      Probiotic Strains Enterococcus faecalis NM815, E. faecalis NM915, and E. faecium
      NM1015: Novel Candidates to Control C. difficile Infection (CDI).
AB  - This study is aimed at the isolation, identification, and characterization of
      potential probiotic strains capable of inhibiting Clostridium difficile in vitro
      and in vivo. Twenty isolates were isolated from infant fecal samples and screened
      against C. difficile using their cell-free supernatant. Only three isolates
      showed maximum inhibition from 56.05 to 60.60%, thus they were characterized for
      probiotic properties and safety. The results obtained approved their tolerance to
      the gastrointestinal tract conditions and safety profile. They were identified by
      sequencing 16S rRNA as Enterococcus faecalis NM815, E. faecalis NM915, and
      Enterococcus faecium NM1015. For in vivo evaluation, a viable mixture of these
      three strains (109 CFU/mL) was administrated to a group of mice (treated group)
      in daily dose for 14 days, then followed by challenge with viable C. difficile
      (105 CFU/mL) in daily dose for 7 days, then a second administration of a viable
      mixture of the three strains was done daily for 7 days. In addition, the control
      group was administered PBS buffer only and the untreated group received PBS
      buffer instead of the probiotic mixture before and after the challenge with C.
      difficile. The results obtained from histological analysis confirmed the
      effectiveness of our three potential probiotic strains which expressed inhibition
      of C. difficile and maintained the structural integrity of the liver and
      intestinal cells.

PMID- 28497218
TI  - To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet
      dressing for the treatment of patients with diabetic foot ulcers: a randomized
      clinical trial.
AB  - The authors aimed to evaluate the efficacy of an advanced wound matrix (Integra
      Flowable Wound Matrix, Integra LifeScience Corp, Plainsboro, NJ, USA) for
      treating wounds with irregular geometries versus a wet dressing in patients with
      diabetic foot ulcers. Sixty patients with diabetic foot ulcers (Grades 3 Wagner)
      were included in this randomized clinical trial. The study was conducted in the
      General Surgery Unit and Geriatric of the Second University of Naples, Italy, in
      the last 12 months. Forty-six cases of diabetic foot ulcers were equally and
      randomly divided into control and test groups. The first group treated with
      Integra Flowable Wound Matrix, while the control group with a wet dressing. Both
      groups were evaluated once a week for 6 weeks to value the degree of
      epithelialization and granulation tissue of the wound. The complete healing rate
      in the whole study population was 69.56% (Integra Flowable Wound Matrix group,
      86.95%, control group, 52.17%; p = 0.001). Amputation and rehospitalization rates
      were higher in the control group compared to the first group, therefore, the
      difference was statistically significant (p = 0.0019; p = 0.028, respectively).
      The Integra Flowable Wound Matrix, was significantly superior, compared to the
      wet dressing, by promoting the complete healing of diabetic foot ulcers. Ease of
      use, absence of adverse effects, and a facilitated wound healing process are
      among the properties of the matrix. These characteristics make it appropriate in
      the management of diabetic foot ulcers. Additional research will shed more light
      on the promising advantages of this material in healing diabetic foot ulcers.

PMID- 28497220
TI  - CT-P10 (TruximaTM): A Rituximab Biosimilar.
AB  - CT-P10 (TruximaTM) is the first biosimilar of the reference monoclonal anti-CD20
      antibody rituximab. It is approved for use in all indications for which reference
      rituximab is approved, including follicular lymphoma (FL), diffuse large B-cell
      non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis (RA),
      granulomatosis with polyangiitis and microscopic polyangiitis. CT-P10 has similar
      physicochemical and pharmacodynamic properties to those of reference rituximab,
      and the pharmacokinetic biosimilarity of the agents has been shown in patients
      with RA or FL. CT-P10 demonstrated clinical efficacy equivalent to that of
      reference rituximab in patients with RA, and was generally well tolerated in this
      population as well as in patients with FL. The tolerability, immunogenicity and
      safety profiles of CT-P10 were similar to those of reference rituximab, and
      switching from reference rituximab to CT-P10 had no impact on safety or efficacy.
      The role of reference rituximab in the management of autoimmune conditions and
      cancers is well established and CT-P10 provides an effective biosimilar
      alternative for patients requiring rituximab therapy.

PMID- 28497219
TI  - Robot-assisted adrenalectomy: indications and drawbacks.
AB  - Adrenal tumors can vary from a benign adrenocortical adenoma with no hormonal
      secretion to a secretory adrenocortical malignancy (adrenocortical carcinoma) or
      a hormone-secreting tumor of the adrenal medulla (pheochromocytoma). Currently,
      laparoscopic adrenalectomy is regarded as the preferred surgical approach for the
      management of most adrenal surgical disorders, although there are no prospective
      randomized trials comparing this technique with open adrenalectomy. However,
      widespread adoption of robotic technology has positioned robotic adrenalectomy as
      an option in some medical centers. Speculative advantages associated with the use
      of the robotic system have rarely been evaluated in clinical settings and cost
      increase remains an important drawback associated with robotic surgery. This
      review summarizes current available data regarding robotic transperitoneal
      adrenalectomy including its indications, advantages, limitations, and comparison
      with conventional laparoscopic adrenalectomy. We believe that the use of a
      robotic system seems to be useful especially in more difficult patients with
      larger tumors, truncal paragangliomas, and bilateral and/or partial
      adrenalectomies. Overall, we believe that overcosts due to robotic system use
      could be balanced by hospital stay decrease, patients' referral increase,
      improved postoperative outcomes in more difficult patients and ergonomics for the
      surgeon. However, we also believe that the current surgical intuitive business
      model is counterproductive, because there are no available strong clinical data
      that could balance overcosts associated with the use of the robotic system.

PMID- 28497221
TI  - Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and
      Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged
      with Both Agents.
AB  - BACKGROUND: During two pivotal clinical trials of the infliximab biosimilar CT
      P13 (PLANETAS and PLANETRA), antidrug antibodies (ADAs) and neutralising
      antibodies (NAbs) were detected in the sera of patients treated with CT-P13 and
      the reference product (RP; Remicade). OBJECTIVE: The aim was to assess the
      comparability of Remicade- and CT-P13-tagged immunoassays for the detection of
      ADAs and NAbs using data from these trials, in order to determine the cross
      reactivity of CT-P13 and RP ADAs. METHODS: Sera from patients with rheumatoid
      arthritis and ankylosing spondylitis were analysed using an
      electrochemiluminescence (ECL) bridging assay or Gyros immunoassay, tagged with
      Remicade or CT-P13 at screening, weeks 14, 30 and 54, and the end of study visit.
      NAb titre was compared at screening and weeks 14 and 30. The proportion of cross
      reactive samples was determined and an inter-rater agreement analysis performed
      to assess the concordance of results between assays. RESULTS: In PLANETAS, 93.1%
      (94/101) of RP ADA-positive samples and 93.0% (93/100) of RP NAb-positive samples
      cross-reacted with CT-P13; 99.0% (103/104) of CT-P13 ADA-positive and 98.0%
      (98/100) of CT-P13 NAb-positive samples cross-reacted with the RP. In PLANETRA,
      94.7% (426/450) of RP ADA-positive samples and 94.3% (415/440) of RP NAb-positive
      samples cross-reacted with CT-P13, and 96.6% (458/474) of CT-P13 ADA-positive and
      96.4% (452/469) of CT-P13 NAb-positive samples cross-reacted with the RP. In both
      studies, there was strong agreement in outcome between assays at all post
      screening time points (PLANETAS: Cohen's kappa 0.89-0.98 for ADA, 0.86-0.98 for
      NAb; PLANETRA: 0.92-0.94 for both ADA and NAb, all p < 0.001). Significant
      concordance between assays was observed for NAb titre at weeks 14 and 30
      (PLANETAS: Spearman's rho 0.73 and 0.74, respectively; PLANETRA: 0.61 and 0.72,
      respectively; all p < 0.001). CONCLUSIONS: This study has demonstrated that ADAs
      and NAbs against CT-P13 and RP are cross-reactive, indicating that CT-P13 and RP
      share immunodominant epitopes.

PMID- 28497222
TI  - Interleukin-1 Blockade: An Update on Emerging Indications.
AB  - Interleukin (IL)-1 is a pro-inflammatory cytokine that induces local and systemic
      inflammation aimed to eliminate microorganisms and tissue damage. However, an
      increasing number of clinical conditions have been identified in which IL-1
      production is considered inappropriate and IL-1 is part of the disease etiology.
      In autoinflammatory diseases, gout, Schnitzler's syndrome, and adult-onset
      Still's disease, high levels of inappropriate IL-1 production have been shown to
      be a key process in the etiology of the disease. In these conditions, blocking IL
      1 has proven very effective in clinical studies. In other diseases, IL-1 has
      shown to be present in disease process but is not the central driving force of
      inflammation. In these conditions, including type 1 and 2 diabetes mellitus,
      acute coronary syndrome, amyotrophic lateral sclerosis, and several neoplastic
      diseases, the benefits of IL-1 blockade are minimal or absent.

PMID- 28497223
TI  - Successful endovascular treatment of popliteal artery entrapment syndrome: a case
      report with 3-years follow-up.
AB  - Popliteal artery entrapment syndrome (PAES) is a rare cause of lower extremity
      arterial ischemia, especially in elder patients. At present, the role of the
      endovascular technique for PAES is still mainly auxiliary, there is no successful
      case treated successfully by endovascular treatment without open surgery, and
      also the long-term follow-up after endovascular treatment are lacking. We
      successfully treated a 51-year-old man with pale, cold right foot by endovascular
      therapy only, including percutaneous transluminal angioplasty and catheter
      directed thrombolysis. After endovascular treatment, the ABI of the right leg
      increased from 0.41 to 0.85, and the patient return to his life without
      claudication. Computed tomography angiography demonstrated the diagnosis of PAES.
      The 3-year follow-up showed a good clinical outcome, suggesting that for certain
      type of PAES, endovascular treatment alone may achieve good results. However,
      this result still requires confirmation in a large-sample study.

PMID- 28497224
TI  - Bone density, microarchitecture, and material strength in chronic kidney disease
      patients at the time of kidney transplantation.
AB  - : Bone health is assessed by bone mineral density (BMD). Other techniques such as
      trabecular bone score and microindentation could improve the risk of fracture's
      estimation. Our chronic kidney disease (CKD) patients presented worse bone health
      (density, microarchitecture, mechanical properties) than controls. More than BMD
      should be done to evaluate patients at risk of fracture. INTRODUCTION: BMD
      measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health
      in end-stage renal disease (ESRD) patients. Recently, trabecular bone score (TBS)
      and microindentation that can measure microarchitectural and mechanical
      properties of bone have demonstrated better correlation with fractures than DXA
      in different populations. We aimed to characterize bone health (BMD, TBS, and
      strength) and calcium/phosphate metabolism in a cohort of 53 ESRD patients
      undergoing kidney transplantation (KT) and 94 controls with normal renal
      function. METHODS: Laboratory workout, lumbar spine/hip BMD measurements (using
      DXA), lumbar spine TBS, and bone strength were carried out. The latter was
      assessed with an impact microindentation device, standardized as percentage of a
      reference value, and expressed as bone material strength index (BMSi) units.
      Multivariable linear regression was used to study differences between cases and
      controls adjusted by age, gender, and body mass index. RESULTS: Among cases,
      serum calcium was 9.6 +/- 0.7 mg/dl, phosphorus 4.4 +/- 1.2 mg/dl, and intact
      parathyroid hormone 214 pg/ml [102-390]. Fourteen patients (26.4%) had prevalent
      asymptomatic fractures in spinal X-ray. BMD was significantly lower among ESRD
      patients compared to controls: lumbar 0.966 +/- 0.15 vs 0.982 +/- 0.15 (adjusted
      p = 0.037), total hip 0.852 +/- 0.15 vs 0.902 +/- 0.13 (adjusted p < 0.001), and
      femoral neck 0.733 +/- 0.15 vs 0.775 +/- 0.12 (adjusted p < 0.001), as were TBS
      (1.20 [1.11-1.30] vs 1.31 [1.19-1.43] (adjusted p < 0.001)) and BMSi (79 [71.8
      84.2] vs 82. [77.5-88.9] (adjusted p = 0.005)). CONCLUSIONS: ESRD patients
      undergoing transplant surgery have damaged bone health parameters (density,
      microarchitecture, and mechanical properties) despite acceptably controlled
      hyperparathyroidism. Detecting these abnormalities may assist in identifying
      patients at high risk of post-transplantation fractures.

PMID- 28497225
TI  - Development of a rapid HRM qPCR for the diagnosis of the four most prevalent
      Plasmodium lineages in New Zealand.
AB  - Although wildlife rehabilitation and translocations are important tools in
      wildlife conservation in New Zealand, disease screening of birds has not been
      standardized. Additionally, the results of the screening programmes are often
      difficult to interpret due to missing disease data in resident or translocating
      avian populations. Molecular methods have become the most widespread method for
      diagnosing avian malaria (Plasmodium spp.) infections. However, these methods can
      be time-consuming, expensive and are less specific in diagnosing mixed
      infections. Thus, this study developed a new real-time PCR (qPCR) method that was
      able to detect and specifically identify infections of the three most common
      lineages of avian malaria in New Zealand (Plasmodium (Novyella) sp. SYAT05,
      Plasmodium elongatum GRW6 and Plasmodium spp. LINN1) as well as a less common,
      pathogenic Plasmodium relictum GRW4 lineage. The assay was also able to discern
      combinations of these parasites in the same sample and had a detection limit of
      five parasites per microlitre. Due to concerns relating to the presence of the
      potentially highly pathogenic P. relictum GRW4 lineage in avian populations, an
      additional confirmatory high resolution (HRM) qPCR was developed to distinguish
      between commonly identified P. elongatum GRW6 from P. relictum GRW4. The new qPCR
      assays were tested using tissue samples containing Plasmodium schizonts from
      three naturally infected dead birds resulting in the identified infection of P.
      elongatum GRW6. Thus, these rapid qPCR assays have shown to be cost-effective and
      rapid screening tools for the detection of Plasmodium infection in New Zealand
      native birds.

PMID- 28497226
TI  - Anisakis haemoglobin is a main antigen inducing strong and prolonged
      immunoreactions in rats.
AB  - Anisakis simplex larvae are well known to cause gastrointestinal and allergic
      manifestations after ingestion of parasitized raw or undercooked seafood. The
      antibody recognition dynamics against the components of Anisakis larval antigen
      after primary and re-infection with Anisakis live larvae remain unclear. For this
      study, immunoblot analyses of serum IgG, IgE, and IgM against Anisakis larval
      somatic extract were performed in rats that had been orally inoculated with A.
      simplex live larvae. Multiple antigen fractions were recognized after primary
      infection. Their reaction was enhanced after re-infection. Antibody recognition
      was observed for 12 weeks after re-infection. The fraction of approximately 35
      kDa contained a main antigen that induced strong and prolonged immunoreactions in
      IgG and IgE. The antibody reaction to this fraction appeared to be enhanced after
      inoculation of larval homogenates. This fraction was heat tolerant with boiling
      for 30 min. The fraction was spotted by immunoblotting after two-dimensional
      electrophoresis and was identified as Anisakis haemoglobin (Ani s 13) using mass
      spectrometry analysis. The amino acid sequences of haemoglobin mRNAs from two A.
      simplex sensu stricto and one Anisakis pegreffii were identified by RACE-PCR.
      They differed from those of two isolates of Pseudoterranova decipiens and A.
      pegreffii. Results of this study show that Anisakis haemoglobin, which is known
      to be a major allergen of A. simplex, induces strong and prolonged immunoreaction
      in rats. This report is the first to show the amino acid sequence variation of
      Anisakis haemoglobin mRNA between A. simplex sensu stricto and A. pegreffii.

PMID- 28497227
TI  - Seroprevalence of Neospora caninum and Toxoplasma gondii in exotic ruminants and
      camelids in the Czech Republic.
AB  - Neospora caninum and Toxoplasma gondii are the protozoan parasites with
      definitive hosts from order Carnivora. Due to vertical transmission, both
      parasites can cause abortions and neonatal mortality that lead to significant
      productive and economic losses in the domestic ruminants. The aim of this study
      was to describe N. caninum and T. gondii seroprevalence in the group of
      frequently farmed captive exotic ruminants (n = 184) including Bovidae (barbary
      sheep, bezoar goat, common eland, American bison, water buffalo, and yak) and
      Camelidae (bactrian camel, guanaco, llama, and alpaca). Antibodies were tested by
      indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay
      (ELISA). Higher prevalence of T. gondii antibodies (31% in IFAT and 52% in ELISA)
      was detected compared to N. caninum (24% in IFAT and 17% in cELISA). Mixed
      infection was found in 18 (10%) and 22 (12%) animals by IFAT and ELISA,
      respectively. Higher seroprevalence of both N. caninum and T. gondii was found in
      Camelidae compared to Bovidae. To author knowledge, this is the first detection
      of T. gondii and N. caninum antibodies in common elands and bezoar goats.

PMID- 28497229
TI  - In vitro assessment of arsenic mobility in historical mine waste dust using
      simulated lung fluid.
AB  - Exposure studies have linked arsenic (As) ingestion with disease in mining
      affected populations; however, inhalation of mine waste dust as a pathway for
      pulmonary toxicity and systemic absorption has received limited attention. A
      biologically relevant extractant was used to assess the 24-h lung
      bioaccessibility of As in dust isolated from four distinct types of historical
      gold mine wastes common to regional Victoria, Australia. Mine waste particles
      less than 20 um in size (PM20) were incubated in a simulated lung fluid
      containing a major surface-active component found in mammalian lungs,
      dipalmitoylphosphatidylcholine. The supernatants were extracted, and their As
      contents measured after 1, 2, 4, 8 and 24 h. The resultant As solubility profiles
      show rapid dissolution followed by a more modest increasing trend, with between
      75 and 82% of the total 24-h bioaccessible As released within the first 8 h.
      These profiles are consistent with the solubility profile of scorodite, a
      secondary As-bearing phase detected by X-ray diffraction in one of the
      investigated waste materials. Compared with similar studies, the cumulative As
      concentrations released at the 24-h time point were extremely low (range 297 +/-
      6-3983 +/- 396 ug L-1), representing between 0.020 +/- 0.002 and 0.036 +/- 0.003%
      of the total As in the PM20.

PMID- 28497228
TI  - 18-Des-hydroxy Cytochalasin: an antiparasitic compound of Diaporthe phaseolorum
      92C, an endophytic fungus isolated from Combretum lanceolatum Pohl ex Eichler.
AB  - Chemical investigation of the ethyl acetate extract from the endophytic fungus
      Diaporthe phaseolorum-92C (92C) isolated from the roots of Combretum lanceolatum
      led to the isolation of 18-des-hydroxy Cytochalasin H (compound 1). The
      trypanocidal and schistosomicidal activity and cytotoxicity of the extract from
      92C were evaluated. The schistosomicidal, leishmanicidal, antimicrobial, and
      antioxidant actions, as well as the antitumor activity against the breast cancer
      cells MDA-MB-231 and MCF-7, and the cytotoxicity towards normal human lung
      fibroblasts GM07492A of compound 1 was tested. The extract from 92C (20 MUg/mL)
      exerted potent trypanocidal activity, reducing 82% of the number of amastigotes
      and trypomastigotes of Trypanosoma cruzi. Compound 1 at 50 MUg/mL killed 50% of
      Schistosoma mansoni adult worms. Compound 1 reduced the viability of Leishmania
      amazonenses promastigotes (IC50 = 9.2 MUg/mL) and of the cancer cells MDA-MB-231
      and MCF-7 (IC50 = 17.5 and 8.88 MUg/mL, respectively), presented moderate
      antioxidant activity, and gave IC50 of 2049.7 +/- 39.9 MUg/mL for the
      cytotoxicity towards normal cells GM07492A. This knowledge is highly relevant to
      the search for new promising compounds for therapeutic purposes.

PMID- 28497230
TI  - Heart failure with preserved ejection fraction: a nephrologist-directed primer.
AB  - There is substantial causal and consequential interaction between the ever
      growing heart failure and renal failure patients. Half of the patients with heart
      failure (HF) have preserved left ventricular ejection fraction (HFpEF), which is
      difficult to diagnose and rising in prevalence relative to HF with reduced EF
      (HFpEF). To date, only weight reduction, exercise training, and diuretics have
      been shown to improve exercise tolerance and morbidity in HFpEF. This review aims
      to establish the baseline kidney-related concepts specific to the diagnosis and
      treatment of HFpEF patients and the different aspects of HFpEF and HFpEF in the
      clinical setting.

PMID- 28497231
TI  - T2 mapping and T2* imaging in heart failure.
AB  - Cardiovascular magnetic resonance (CMR) is a versatile imaging modality that
      enables aetiological assessment and provides additional information to that of
      standard echocardiography in a significant proportion of patients with heart
      failure. In addition to highly accurate and reproducible assessment of
      ventricular volumes and replacement fibrosis, multiparametric mapping techniques
      have rapidly evolved to further expand the diagnostic and prognostic applications
      in various conditions ranging from acute inflammatory and ischaemic
      cardiomyopathy, to cardiac involvement in systemic diseases such as sarcoidosis
      and iron overload cardiomyopathy. In this review, we discuss the established role
      of T2* imaging and rapidly evolving clinical applications of myocardial T2
      mapping as quantitative adjuncts to established qualitative imaging techniques.

PMID- 28497232
TI  - Tamoxifen for induction of Cre-recombination may confound fibrosis studies in
      female mice.
AB  - A variety of conditional knock-out mice relying on Tamoxifen-driven ERT2/Cre 
      mediated recombination are available and have been used to study involvement of
      specific genes in kidney disease. However, recent data suggest that Tamoxifen
      itself might attenuate fibrosis when administered during experimental models of
      kidney disease. It has remained unclear whether this still applies also if kidney
      damage is initiated after a wash-out period has been implemented. Here we report
      that the commonly applied regimen of administration of 4 alternate day doses of
      1mg Tamoxifen per mouse until 14 days prior to start of the actual experiment, in
      this case the induction of obstructive nephropathy by Unilateral Ureteral
      Obstruction (UUO), still attenuated fibrosis in female obstructed mouse kidneys,
      whereas this effect was not seen in male obstructed kidneys. Attenuation of
      fibrosis was accompanied by a reduction in nuclear ERalpha positivity despite
      absence of detectable levels of the active tamoxifen metabolite endoxifen
      throughout the UUO experiment. In conclusion, these results indicate that the
      Tamoxifen dosing regimen commonly applied in conditional gene targeting
      experiments might have prolonged confounding effects in female mice through
      attenuation of renal fibrosis independent of modulation of the expression of the
      targeted gene(s).

PMID- 28497234
TI  - The 2017 CALDAR Summer Institute and International Conference Promoting Global
      Health-Precision Research in Substance Abuse, HIV, and Care.
AB  - The 2017 CALDAR Summer Institute on Longituidnal Research and International
      Conference Series to Promote Global Health will take place in Los Angeles
      Universal City, CA, USA from August 15 to August 17, 2017. The conference will
      present a selection of the lastest and most current reseach in the areas of
      addiction, HIV, and related treatment.

PMID- 28497233
TI  - Standardization and Optimization of Intraoperative Molecular Imaging for
      Identifying Primary Pulmonary Adenocarcinomas.
AB  - PURPOSE: Intraoperative molecular imaging (IMI) is an emerging technology used to
      locate pulmonary adenocarcinomas and identify positive margins during surgery.
      Background noise and tissue autofluorescence have been major obstacles. The goal
      of this study is to optimize the image quality of folate receptor alpha (FRalpha)
      targeted IMI for pulmonary adenocarcinomas by modifying emission data.
      PROCEDURES: A total of 15 lung cancer patients were enrolled in a pilot study. In
      the first cohort, FRalpha upregulation within pulmonary adenocarcinoma tumors was
      confirmed by analyzing specimens from five pulmonary adenocarcinoma patients with
      flow cytometry and immunohistochemistry. Next, in a cohort of five additional
      patients, autofluorescence of intrathoracic structures and tissues was
      quantified. Lastly, five patients with tumors at various depths from the pleural
      surface were enrolled and received the FRalpha-targeted optical contrast agent,
      EC17. In this final cohort, resected pulmonary adenocarcinomas were imaged at a
      wide range of fluorescence exposure times (0 to 200 ms), various laser powers,
      and with unique filter configurations. Tumor-to-noise ratio (TNR) for images was
      generated using region of interest software. RESULTS: Pulmonary adenocarcinomas
      highly express FRalpha. Significant autofluorescence from native thoracic tissues
      was found with the highest fluorescent signals at the bronchial stump (547 +/-
      98, range 423-699), the pulmonary artery (267 +/- 64, range 200-374), and
      cortical bone (266 +/- 17, range 243-287). High levels of autofluorescence were
      appreciated after systemic administration of EC17; however, TNR was improved by
      altering exposure settings at the time of the imaging. Optimal fluorescent
      exposure time occurs at 40 ms (25 frames/s). CONCLUSIONS: Exposure properties can
      be manipulated to maximize TNR thus allowing for successful intraoperative
      detection of pulmonary adenocarcinomas during surgery. Optimization of the
      conditions for intraoperative molecular imaging sets the stage for future
      clinical trials utilizing targeted IMI techniques which can aid the surgeon at
      the time of cancer resection.

PMID- 28497235
TI  - Spatiotemporal Dynamics of the Cortical Responses Induced by a Prolonged Tactile
      Stimulation of the Human Fingertips.
AB  - The sense of touch is fundamental for daily behavior. The aim of this work is to
      understand the neural network responsible for touch processing during a prolonged
      tactile stimulation, delivered by means of a mechatronic platform by passively
      sliding a ridged surface under the subject's fingertip while recording the
      electroencephalogram (EEG). We then analyzed: (i) the temporal features of the
      Somatosensory Evoked Potentials and their topographical distribution bilaterally
      across the cortex; (ii) the associated temporal modulation of the EEG frequency
      bands. Long-latency SEP were identified with the following physiological sequence
      P100-N140-P240. P100 and N140 were bilateral potentials with higher amplitude in
      the contralateral hemisphere and with delayed latency in the ipsilateral side.
      Moreover, we found a late potential elicited around 200 ms after the stimulation
      was stopped, which likely encoded the end of tactile input. The analysis of
      cortical oscillations indicated an initial increase in the power of theta band (4
      7 Hz) for 500 ms after the stimulus onset followed a decrease in the power of the
      alpha band (8-15 Hz) that lasted for the remainder of stimulation. This decrease
      was prominent in the somatosensory cortex and equally distributed in both
      contralateral and ipsilateral hemispheres. This study shows that prolonged
      stimulation of the human fingertip engages the cortex in widespread bilateral
      processing of tactile information, with different modulations of the theta and
      alpha bands across time.

PMID- 28497236
TI  - [Atrial fibrillation].

PMID- 28497237
TI  - Efficacy of long-term nonsteroidal antiinflammatory drug treatment on magnetic
      resonance imaging-determined bone marrow oedema in early, active axial
      spondyloarthritis patients.
AB  - To assess the efficacy of long-term treatment with nonsteroidal antiinflammatory
      drugs (NSAIDs) on bone marrow oedema (BMO) of the sacroiliac joint in newly
      diagnosed axial spondyloarthritis (SpA) with a symptom duration of less than 4
      years, a single-center, open-label study in a cohort of consecutive patients with
      newly diagnosed axial SpA was conducted. Eligible patients had magnetic resonance
      imaging (MRI)-determined BMO of the sacroiliac joint at baseline, had a symptom
      duration of less than 4 years, and were naive to NSAIDs. After the baseline MRI,
      an optimal dose of NSAID was administered for 24 or 48 weeks. BMO of sacroiliac
      joint was quantified by applying the Spondyloarthritis Research Consortium of
      Canada (SPARCC) system. Disease activity was expressed using the Ankylosing
      Spondylitis Disease Activity Score (ASDAS). Primary end points were improvement
      in BMO of sacroiliac joint at week 24 or week 48. Forty-three patients were
      recruited, and 33 patients eventually completed the study, including 10 patients
      having follow-up MRI at week 24 and 23 patients having follow-up MRI at week 48.
      Overall, the mean of SPARCC score decreased from 21.8 +/- 16.1 at baseline to
      10.2 +/- 12.8 at follow-up (p < 0.001). 75.8% of the patients displayed a
      minimally important change, and 30.3% became free of BMO. The mean of ASDAS-CRP
      decreased from 3.1 +/- 1.0 at baseline to 2.1 +/- 1.0 at follow-up (p < 0.001).
      Long-term treatment with optimal dose NSAIDs could significantly alleviate BMO of
      sacroiliac joint in early and active axial SpA.

PMID- 28497240
TI  - In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N
      Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy.
AB  - A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine
      doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential
      for treatment of tumours demonstrating improved efficacy and reduced toxicity.
      The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide
      (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N
      acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer.
      Doxorubicin has a potent and promising anticancer activity; however, severe
      cardiotoxicity limits its application in cancer treatment. By modifying DOX in
      PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo
      anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin
      melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy
      studies were done by comparing tumour volume, body weight, organ index and
      percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX
      at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX
      solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared
      to <50% survival rate for DOX solution. In addition, toxicity studies and
      histopathological studies revealed that while maintaining its cytotoxicity
      towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs.
      Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for
      targeted cancer therapy.

PMID- 28497238
TI  - Obesity-related mortality in France, Italy, and the United States: a comparison
      using multiple cause-of-death analysis.
AB  - OBJECTIVES: We investigate the reporting of obesity on death certificates in
      three countries (France, Italy, and the United States) with different levels of
      prevalence, and we examine which causes are frequently associated with obesity.
      METHODS: We use cause-of-death data for all deaths at ages 50-89 in 2010-2011.
      Since obesity may not be the underlying cause (UC) of death, we compute age- and
      sex-standardized death rates considering all mentions of obesity (multiple causes
      or MC). We use cluster analyses to identify patterns of cause-of-death
      combinations. RESULTS: Obesity is selected as UC in no more than 20% of the
      deaths with a mention of obesity. Mortality levels, whether measured from the UC
      or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death
      combinations are similar across the countries. In addition to strong links with
      cardiovascular diseases and diabetes, we identify several less familiar
      associations. CONCLUSIONS: Considering all mentions on the deaths certificates
      reduces the underestimation of obesity-related mortality based on the UC only. It
      also enables us to describe the various mortality patterns involving obesity.

PMID- 28497239
TI  - Validation of the revised International Prognostic Scoring System in patients
      with myelodysplastic syndrome in Japan: results from a prospective multicenter
      registry.
AB  - The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes
      has been conducting prospective registration, central review, and follow-up study
      for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006.
      Using this database, we retrospectively analyzed the prognosis of patients with
      MDS. As of May 2016, 351 cases were registered in this database, 186 of which
      were eligible for the present study. Kaplan-Meier analysis showed that overall
      survival (OS) curves of the five risk categories stipulated by the revised
      international prognostic scoring system (IPSS-R) were reasonably separated. 2
      year OS rates for the very low-, low-, intermediate-, high-, and very high-risk
      categories were 95, 89, 79, 35, and 12%, respectively. In the same categories,
      incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%,
      respectively. Multivariate analysis revealed that male sex, low platelet counts,
      increased blast percentage (>2%), and high-risk karyotype abnormalities were
      independent risk factors for poor OS. Based on these data, we classified Japanese
      MDS patients who were classified as intermediate-risk in IPSS-R, into the lower
      risk MDS category, highlighting the need for careful assessment of treatments
      within low- and high-risk treatment protocols.

PMID- 28497241
TI  - Fighting against evolution of antibiotic resistance by utilizing evolvable
      antimicrobial drugs.
AB  - Antibiotic resistance is a worldwide public health problem (Bush et al. in Nat
      Rev Microbiol 9:894-896, 2011). The lack of effective therapies against resistant
      bacteria globally leads to prolonged treatments, increased mortality, and
      inflating health care costs (Oz et al. in Mol Biol Evol 31:2387-2401, 2014;
      Martinez in Science 321:365-367, 2008; Lipsitch et al. in Proc Natl Acad Sci USA
      97:1938-1943, 2000; Taubes in Science 321:356-361, 2008; Laxminarayan et al. in
      Lancet, 2016; Laxminarayan et al. in Lancet Infect Dis 13:1057-1098, 2013).
      Current efforts towards a solution of this problem can be boiled down to two main
      strategies: (1) developing of new antimicrobial agents and (2) searching for
      smart strategies that can restore or preserve the efficacy of existing
      antimicrobial agents. In this short review article, we discuss the need for
      evolvable antimicrobial agents, focusing on a new antimicrobial technology that
      utilizes peptide-conjugated phosphorodiamidate morpholino oligomers to inhibit
      the growth of pathogenic bacteria by targeting bacterial genes.

PMID- 28497242
TI  - [New Sepsis-3 definition : Do we have to treat sepsis before we can diagnose it
      from now on?]
AB  - The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis
      3) have been available since the beginning of 2016. SEPSIS-3 completely replaces
      the old SIRS criteria in the definition of sepsis and defines sepsis from now on
      as "life-threatening organ dysfunction caused by a dysregulated host response to
      infection". However, it seems questionable whether in clinical practice the new
      definition is really superior to the old one. The most important question is the
      following: Is it helpful to have a definition that first recognizes a patient
      once organ dysfunction has occurred and the patient already needs intensive care?

PMID- 28497243
TI  - ["Kids Save Lives"-resuscitation training for schoolchildren : Systematic
      review].
AB  - BACKGROUND: Even in western developed countries, the probability of survival
      after out-of-hospital cardiac arrest (OHCA) is only 6-10%. In order to improve
      survival after OHCA, early initiation of cardiopulmonary resuscitation (CPR) by
      laypersons is essential. Introduction of CPR training in schoolchildren seems to
      be effective to increase lay-CPR rates. OBJECTIVE: The objective of the present
      investigation was to elucidate educational aspects of teaching schoolchildren in
      CPR and to summarize campaigns related to a comprehensive establishment of lay
      CPR worldwide. MATERIALS AND METHODS: A literature research in PubMed was
      performed, the cutoff date was 27 February 2017. Overall, 192 abstracts were
      analyzed; 51 articles were considered relevant and included in the manuscript. An
      additional keyword research in Google revealed >230,000 entries, and 20 of those
      were included in the present manuscript. RESULTS: A minimum age of 12-13 years is
      required to achieve a comparable quality of CPR to adult basic life support
      (BLS). Key issues are (i) the correct detection of a cardiac arrest, (ii) a
      correctly performed call for help, (iii) thoracic compressions and (iv) if
      applicable, the initiation of adequate mouth-to-mouth ventilation. Practical
      training showed a significantly higher CPR quality compared to theoretical
      training only or to the use of instruction or online videos only. Worldwide
      implementation of a 2-h BLS training per year in children from the age of 12 or
      younger is recommended by the "Kids Save Lives"- statement since 2015. In
      Germany, implementation at the level of the federal states has progressed to
      different degrees.

PMID- 28497244
TI  - Invisible Voices: An Intersectional Exploration of Quality of Life for Elderly
      South Asian Immigrant Women in a Canadian Sample.
AB  - Despite the emerging presence of South Asian elderly population in Canada, there
      continues to be a paucity of research concerning the immigration and
      acculturation experiences of these marginalized elderly populations and their
      quality of life. This research builds knowledge of the quality of life
      experiences faced by South Asian elderly immigrant women residing in Canada using
      an intersectional analytical framework. While there is a gradually developing
      body of research regarding elder persons globally, the present research is unique
      in that explores challenges, stresses and strains, and builds an understanding of
      the treatment of older ethnic minorities and immigrant families. Furthermore,
      this research has implications for policies and practices governing these growing
      aging populations. Finally, this research gives voice to a "silenced" and
      invisible group of elders whose stories may help to make improvements in the
      quality of living and well-being for the aging South Asian immigrant population
      in Canada.

PMID- 28497245
TI  - Single species growth consuming inorganic carbon with internal storage in a
      poorly mixed habitat.
AB  - This paper presents a PDE system modeling the growth of a single species
      population consuming inorganic carbon that is stored internally in a poorly mixed
      habitat. Inorganic carbon takes the forms of "CO2" (dissolved CO2 and carbonic
      acid) and "CARB" (bicarbonate and carbonate ions), which are substitutable in
      their effects on algal growth. We first establish a threshold type result on the
      extinction/persistence of the species in terms of the sign of a principal
      eigenvalue associated with a nonlinear eigenvalue problem. If the habitat is the
      unstirred chemostat, we add biologically relevant assumptions on the uptake
      functions and prove the uniqueness and global attractivity of the positive steady
      state when the species persists.

PMID- 28497246
TI  - Neural Correlates of Explicit Versus Implicit Facial Emotion Processing in ASD.
AB  - The underlying neural mechanisms of implicit and explicit facial emotion
      recognition (FER) were studied in children and adolescents with autism spectrum
      disorder (ASD) compared to matched typically developing controls (TDC). EEG was
      obtained from N = 21 ASD and N = 16 TDC. Task performance, visual (P100, N170)
      and cognitive (late positive potential) event-related-potentials, as well as
      coherence were compared across groups. TDC showed a task-dependent increase and a
      stronger lateralization of P100 amplitude during the explicit task and task
      dependent modulation of intra-hemispheric coherence in the beta band. In
      contrast, the ASD group showed no task dependent modulation. Results indicate
      disruptions in early visual processing and top-down attentional processes as
      contributing factors to FER deficits in ASD.

PMID- 28497247
TI  - [Medial closed wedge osteotomy of the distal femur in biplanar technique and a
      specific plate fixator].
AB  - OBJECTIVE: Correction of distal femur deformity by closed-wedge biplanar
      osteotomy. INDICATIONS: Metaphyseal frontal plane deformities of the femur.
      CONTRAINDICATIONS: Osteoarthritis of the contralateral compartment, total loss of
      the contralateral meniscus, acute/chronic infection, limited range-of-motion,
      poor soft-tissue conditions at site of surgery. SURGICAL TECHNIQUE: Skin incision
      at metaphyseal area of femur. Local exposure of bone. Marking of planned
      osteotomies. Incomplete posterior osteotomies, complete anterior osteotomy. Wedge
      removal and closure. Radiological control of alignment. Fixation with specific
      plate fixator for the medial femur (TomoFix MDF). Submuscular plate fixation.
      Wound closure. POSTOPERATIVE MANAGEMENT: Elastic bandage, suction drain removal
      and walking with crutches on day 1. Partial weight bearing (15 kg) for the first
      4 weeks; X-ray control on day 3 and 4 weeks after surgery, walking without
      crutches depending on healing of osteotomy. Thrombosis prophylaxis. RESULTS: From
      January 2005 to October 2008, 60 patients were treated. Average wedge size 7.6
      mm; age 39.7 years; mean follow-up 21 months; 7 revision surgeries: 3
      delayed/nonunion of the osteotomy, one superficial infection, one deep infection,
      one hematoma, and one fracture proximal of the internal plate fixator. Tegner
      activity score pre-/postoperative 2.8 (1-4)/5.6 (2-9); VAS score pre
      /postoperative 6.8 (2-9)/3.1 (0-8). From 2014-2015, 107 femur osteotomies
      performed: 4 delayed healing, one plate breakage. Healing of all other
      osteotomies in 4-6 weeks. No loss of range-of-motion with the muscle-sparing
      surgical technique.

PMID- 28497249
TI  - The honeymoon period repeatedly appears in two cases of type 1 diabetes mellitus.

PMID- 28497248
TI  - [Aseptic loosening of total ankle replacement : One-stage revision ankle
      arthroplasty].
AB  - OBJECTIVE: To revise one or both loosened prosthesis components, to achieve
      postoperative pain relief, and preserve ankle range of motion. INDICATIONS:
      Aseptic loosening of the tibial and/or talar ankle prosthesis components without
      substantial bone defect of the tibial or talar bone stock. CONTRAINDICATIONS:
      General surgical or anesthesiological risks, infections, critical soft tissue
      conditions, nonmanageable hindfoot instability, neurovascular impairment of the
      lower extremity, neuroarthropathy (e. g. Charcot arthropathy), substantial
      nonreconstructable osseous defects with or without cysts on the tibial and/or
      talar side, non-compliance, patients with primary total ankle replacement (TAR)
      using intramedullary fixation (stem fixation), patients with severely reduced
      bone quality, insulin-dependent diabetes mellitus, smoking, unrealistic patient
      expectations, patients with high activity in sports. SURGICAL TECHNIQUE: Exposure
      of the ankle joint using the previous incision (anterior or lateral transfibular
      approach). Mobilization and removal of loosened prosthesis component. Careful
      debridement of bone stock at bone-prosthesis interface. Determination of
      prosthesis component size. Implantation of definitive prosthesis components.
      Wound closure in layers. POSTOPERATIVE MANAGEMENT: A soft wound dressing is used.
      Thromboprophylaxis is recommended. Patient mobilization starts at postoperative
      day 1 with 15 kg partial weight bearing using a stabilizing walking boot or cast
      for 6 weeks. Following clinical and radiographic follow-up at 6 weeks, full
      weight bearing is initiated gradually. RESULTS: Between January 2007 and December
      2012 a one-stage revision TAR was performed in 14 patients with a mean age of
      52.7 +/- 12.0 years (29.8-70.5 years). The indication for revision surgery was
      aseptic loosening of one or both prosthesis components. The mean time between the
      initial TAR and revision surgery was 5.9 +/- 2.9 years (2.0-11.5 years). In 2
      patients a tibiotalocalcaneal arthrodesis was performed due to painful aseptic
      loosening of revision TAR. In all patients a significant pain relief was
      observed.

PMID- 28497250
TI  - People's Understanding of Verbal Risk Descriptors in Patient Information
      Leaflets: A Cross-Sectional National Survey of 18- to 65-Year-Olds in England.
AB  - INTRODUCTION: Evidence suggests the current verbal risk descriptors used to
      communicate side effect risk in patient information leaflets (PILs) are
      overestimated. OBJECTIVES: The aim was to establish how people understand the
      verbal risk descriptors recommended for use in PILs by the European Commission
      (EC), and alternative verbal risk descriptors, in the context of mild and severe
      side effects. METHODS: A cross-sectional online survey was carried out by a
      market research company recruiting participants aged between 18 and 65 years
      living in England. Data were collected between 18 March and 1 April 2016.
      Participants were given a hypothetical scenario regarding the risk of mild or
      severe medication side effects and asked to estimate how many out of 10,000
      people would be affected for each of the verbal risk descriptors being tested.
      RESULTS: A total of 1003 participants were included in the final sample. The
      risks conveyed by the EC recommended verbal risk descriptors were greatly
      overestimated by participants. Two distinct distributions were apparent for
      participant estimates of side effect risks: those for 'high risk' verbal
      descriptors (e.g. 'common', 'likely', 'high chance') and those for 'low risk'
      verbal descriptors (e.g. 'uncommon', 'unlikely', 'low chance'). Within these two
      groups, the distributions were near to identical regardless of what adverb (e.g.
      very, high, fair) or adjective (e.g. common, likely, chance) was used. The EC
      recommended verbal risk descriptors were more likely to be understood in
      accordance with their intended meanings when describing severe side effects. Very
      few demographic or psychological factors were consistently associated with how
      well participants understood the EC recommended verbal risk descriptors.
      DISCUSSION: The current verbal risk descriptors used in PILs are ineffective at
      best and misleading at worst. Discontinuing the use of verbal risk descriptors
      would limit the likelihood of people overestimating the risk of side effects.

PMID- 28497251
TI  - Minimally Invasive Surgery for Complicated Diverticulitis.

PMID- 28497252
TI  - Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially
      Curable?
AB  - BACKGROUND: Jaundice as a presenting symptom of gallbladder cancer has
      traditionally been considered to be a sign of advanced disease, inoperability,
      and poor outcome. However, recent studies have demonstrated that a small subset
      of these patients can undergo resection with curative intent. METHODS: Patients
      with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic
      institutions were stratified based on the presence of jaundice at presentation
      (defined as bilirubin >=4 mg/ml or requiring preoperative biliary drainage).
      Perioperative morbidity, mortality, and overall survival were compared between
      jaundiced and non-jaundiced patients. RESULTS: Of 400 gallbladder cancer patients
      with available preoperative data, 108 (27%) presented with jaundice while 292
      (73%) did not. The fraction of patients who eventually underwent curative-intent
      resection was much lower in the presence of jaundice (n = 33, 30%) than not (n =
      218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative
      morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation
      (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was
      not significantly higher. Overall survival after resection was worse in jaundiced
      patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within
      the jaundiced patients revealed a more favorable survival after resection in the
      presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the
      absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). CONCLUSION:
      Jaundice is a powerful preoperative clinical sign of inoperability and poor
      outcome among gallbladder cancer patients. However, some of these patients may
      still achieve long-term survival after resection, especially when preoperative
      CA19-9 levels are low and no lymphovascular invasion is noted pathologically.

PMID- 28497253
TI  - Effects of juvenile hormone analogue (methoprene) and 20-hydroxyecdysone on
      reproduction in Polygonia c-aureum (Lepidoptera: Nymphalidae) in relation to
      adult diapause.
AB  - We investigated the effects of juvenile hormone analogue (methoprene) and 20
      hydroxyecdysone on female and male reproduction in a nymphalid butterfly,
      Polygonia c-aureum. This butterfly has a facultative adult diapause controlled by
      the corpora allata and brain. Methoprene seems to terminate reproductive
      diapause, although transplantation experiments indicate that the activity of the
      corpora allata does not affect male mating behavior Endo (Dev Growth Differ 15:1
      10, 1973a), suggesting that the brain may be involved in diapause. We found that
      exposure to methoprene promoted the development of ovaries and of the male
      accessory glands and simplex. On the other hand, exposure to 20-hydroxyecdysone
      did not promote the development of female and male reproductive organs and
      eupyrene sperm movement from the testis to the duplex in the adult stage.
      Ecdysteroid titer in both sexes was consistently low in adults. These results
      suggest that imaginal diapause is largely regulated by juvenile hormone in this
      butterfly.

PMID- 28497255
TI  - [Acute focal neurological deficits in the emergency room].
AB  - A focal neurological deficit with sudden onset or rapid progression is an
      alarming symptom indicating a neurological disorder with often urgent need for
      treatment. Particularly in the emergency room, where time and resources are
      limited, it is necessary to rapidly assign such a focal neurological deficit to a
      certain syndrome and to define a suspected diagnosis in order to execute the
      correct diagnostics and emergency therapy. In this article, we highlight frequent
      and typical neurological disorders presenting in the emergency room and their
      corresponding focal neurological deficits. The article and a suggested algorithm
      are to guide less-experienced colleagues to find quick steps from acute symptoms
      to diagnosis and emergency treatment of frequent and relevant neurological
      disorders in the emergency room.

PMID- 28497254
TI  - 9-Phenanthrol modulates postinhibitory rebound and afterhyperpolarizing
      potentials in an excitatory motor neuron of the medicinal leech.
AB  - Postinhibitory rebound (PIR) responses in leech dorsal excitatory motor neurons
      (cell DE-3) are eliminated by Ca2+ channel blockers but also exhibit a strong
      dependence on extracellular Na+. These features could be explained by a voltage
      gated Ca2+ current acting in concert with a Ca2+-activated nonspecific current
      (ICAN). In vertebrates, ICAN is associated with TRPM4 channels which are blocked
      selectively by 9-phenanthrol. Here, we show that 9-phenanthrol selectively
      inhibits a late phase of PIR and simultaneously enhances afterhyperpolarizing
      potentials (AHPs). Bath application of NNC 55-0396 or Cd2+ combined with ion
      substitution experiments indicate that a low-voltage-activated Ca2+ current plays
      a key role in generating PIR and that Ca2+ influx through low- or high-voltage
      activated Ca2+ channels can trigger AHPs via activation of a Ca2+-dependent K+
      current. We also demonstrate modulation of rebound responses by other ICAN
      blockers such as gadolinium and flufenamic acid, as well as the calmodulin
      antagonist W-7. We discuss how these results provide additional insights into the
      specific types of ionic currents underlying rebound responses of motor neuron DE
      3 in the medicinal leech.

PMID- 28497256
TI  - [Pharmacotherapy of Parkinson's disease : Aspects of drug safety].
AB  - BACKGROUND: This overview focuses on the aspects of the pharmacotherapy of
      Parkinson's disease, which is one of the most common disorders of the nervous
      system. This article presents the complexity of the pharmacotherapy of geriatric
      patients with neurological diseases. OBJECTIVES: Information about the potential
      risk factors and aspects of drug safety in the pharmacotherapy of Parkinson's
      disease. MATERIALS AND METHODS: Selective literature search using PubMed and the
      scientific-clinical experience of the authors. RESULTS: Patients with Parkinson's
      disease are usually geriatric patients with concomitant diseases. As a result
      they are often treated with comedication which leads to a complex medication
      regime with more than five drugs. Such polypharmacy increases the risk of adverse
      drug events due to the rising number of possible interactions and
      contraindications. To control this risk and maintain a safe therapy, certain
      measures should be considered. This implies additional need for educational work
      in order to create awareness regarding potential adverse drug events. In certain
      cases of diagnosed comorbidities or relevant drug prescriptions in the medication
      regime, follow-up examinations should be conducted. CONCLUSION: Specific
      parameters of Parkinson's disease, the health-related quality of life of affected
      patients and the quality of pharmacotherapeutic drug safety can be improved by
      targeted monitoring of the medication regime. As a result, the overall drug
      safety can be increased.

PMID- 28497257
TI  - [Therapy of migranes].
AB  - In migraine attack treatment analgesics such as nonsteroidal anti-inflammatory
      drugs and triptans can be utilized. The efficacy of acute attack treatment is
      relevant to prevent migraine chronification. For prophylactic treatment beta
      blockers, tricyclic antidepressants, flunarizine, antiepileptics and
      onabotulinumtoxin A are available. There is evidence that some other substances
      (e. g. sartans) are also efficacious in this regard. Furthermore, nondrug
      approaches are essential in migraine therapy. Early education and prophylactic
      treatment of patients at risk may prevent from medication overuse headache.
      Noninvasive neuromodulatory approaches as supraorbital or vagal nerve stimulation
      are emerging methods for prophylactic treatment. Ongoing clinical trials
      investigate an oral calcitonin gene-related peptide (CGRP) antagonist for acute
      treatment and several prophylactic monoclonal CGRP or CGRP receptor-antibodies
      regarding safety, side effects and efficacy as new therapeutic options.

PMID- 28497258
TI  - Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with
      Temozolomide in Subjects with Nonhematologic Malignancies.
AB  - BACKGROUND AND OBJECTIVES: Veliparib is an orally active potent poly(ADP-ribose)
      polymerase (PARP) inhibitor currently in phase III clinical trials in solid
      tumors. This phase I study evaluated the pharmacokinetics and mass balance of
      veliparib administered alone and in combination with temozolomide, and assessed
      any potential pharmacokinetic drug-drug interaction between veliparib and
      temozolomide. METHODS: This was an open-label, dose-escalation study of veliparib
      in combination with temozolomide in 42 subjects with nonhematologic malignancies.
      Veliparib was administered orally at doses ranging from 10 to 80 mg twice daily
      on days 1-7, and temozolomide was administered orally at 150-200 mg/m2 once daily
      on days 1-5 of each 28-day cycle. The pharmacokinetics of veliparib, its M8
      metabolite, and temozolomide, as well as urinary excretion of unchanged veliparib
      and its M8 metabolite, were determined. RESULTS: Mean veliparib maximum observed
      plasma concentration (C max) and area under the plasma concentration-time curve
      for the first 6 h postdose (AUC6) values increased dose proportionally in the
      veliparib 10-80 mg twice-daily dose range. The urinary recovery of veliparib dose
      as the unchanged parent compound alone and together with the M8 metabolite was 73
      +/- 18 and 90 +/- 22%, respectively, over a 12-h dosing interval on day 6 of
      Cycle 1. Veliparib and temozolomide pharmacokinetic exposures were not affected
      when administered together. CONCLUSIONS: Veliparib is a Biopharmaceutical
      Classification System (BCS) Class 1 compound, with no less than 90% of the dose
      absorbed and an oral bioavailability of at least 73%. Veliparib is primarily
      eliminated by renal excretion. Veliparib exhibited linear pharmacokinetics in the
      10-80 mg twice-daily dose range. No pharmacokinetic interaction was observed when
      veliparib and temozolomide were administered together. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00526617.

PMID- 28497259
TI  - Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase
      I Dose-Escalation Trial.
AB  - BACKGROUND: Valproic acid, a histone deacetylase inhibitor, has beneficial
      effects in the setting of cancer, neurologic diseases, and traumatic injuries. In
      animal models of traumatic injury, a single dose of valproic acid has been shown
      to reduce mortality. The purpose of this trial was to determine the maximum
      tolerated single dose of intravenous valproic acid in healthy humans. METHODS: A
      double-blinded, placebo-controlled, dose-escalation trial design was used to
      identify dose-limiting toxicities in healthy subjects who received a single dose
      of intravenous valproic acid. Patients were monitored for adverse events and data
      were collected for pharmacokinetic, pharmacodynamic, and safety profiling of
      valproic acid. RESULTS: Fifty-nine healthy subjects (mean 30 +/- 12 years) were
      enrolled. Forty-four subjects received valproic acid in doses from 15 to 150
      mg/kg. The most common adverse events were hypoacusis (n = 19), chills (n = 18),
      and headache (n = 16). The maximum tolerated dose was 140 mg/kg. Dose-limiting
      toxicities included headache and nausea lasting longer than 12 h. No drug-related
      abnormalities were seen in other safety measures including laboratory tests,
      hemodynamic parameters, cardiac rhythm monitoring, and cognitive testing. A two
      compartment model was predictive of valproic acid concentration-time profiles,
      with a strong correlation (R 2 = 0.56) observed between the number of reported
      adverse events and the dose level. CONCLUSIONS: The maximum tolerated dose of
      intravenous valproic acid in healthy subjects is 140 mg/kg. This is significantly
      higher than the previously established maximum tolerated dose of 60-75 mg/kg.
      Next, the safety and tolerability of high-dose valproic acid will be tested in
      trauma patients in hemorrhagic shock. ClinicalTrials.gov Identifier: NCT01951560.

PMID- 28497261
TI  - Othmar Schubiger.

PMID- 28497260
TI  - A Physiologically Based Pharmacokinetic Perspective on the Clinical Utility of
      Albumin-Based Dose Adjustments in Critically Ill Patients.
AB  - INTRODUCTION: In hypo-albuminemia, the extent of albumin binding of a drug
      decreases. The resulting change in plasma protein binding only rarely leads to
      clinically relevant changes in unbound drug exposure. Nevertheless, in the
      critically ill, a tendency to increase dosing of anti-infective therapy is seen
      in patients experiencing hypo-albuminemia. To reconcile basic pharmacological
      principles with current clinical practice, this work presents a pharmacologically
      based pharmacokinetic simulation study to emphasize the (lack of) effect of
      altered plasma protein binding on a drug's concentration-time profile and
      associated pharmacokinetic parameters. METHODS: Four virtual compounds,
      representing a broad chemical space (low/high clearance/volume of distribution),
      were created and administered to a virtual population of normal patients and
      three types of hypo-albuminemic patients in Simcyp(r). The influence of decreased
      plasma protein binding in hypoalbuminemia on the pharmacokinetic parameters and
      profiles of these four compounds was investigated. RESULTS: Simulation results
      showed that while high-clearance compounds suffer from increased unbound exposure
      with decreased plasma protein binding, the unbound exposure of low-clearance
      compounds was unaffected. However, for the subset of low-clearance compounds with
      a small volume of distribution, it appeared that there were still alterations in
      their plasma concentration-time profiles. Since this may lead to different times
      above a minimum inhibitory concentration value, this might affect the bacterial
      killing for some anti-infective drugs. Overall, for any compound involved in the
      simulations, the unbound exposure did not decrease in plasma protein binding
      subjects relative to normal plasma protein binding subjects. DISCUSSION: This
      finding is in line with the few case-controlled studies in the literature. Hence,
      increasing the dose/dosing frequency seems futile and might reduce the benefit
      risk ratio for narrow therapeutic index drugs. Moreover, these simulations
      indicate that when only total plasma concentrations and derived pharmacokinetic
      parameters are considered, incorrect conclusions will be drawn.

PMID- 28497262
TI  - Arterial tortuosity in patients with spontaneous cervical artery dissection.
AB  - PURPOSE: The aim of this study was to test the hypothesis that patients with
      spontaneous cervical artery dissection (CeAD) have increased arterial tortuosity,
      and the objective quantification of such a tortuosity may aid in the
      identification of subjects at increased risk of disease. METHODS: In the setting
      of a hospital-based, case-control study, we used the vertebral tortuosity index
      (VTI) measured on magnetic resonance angiography, a validated method for the
      assessment and quantification of arterial tortuosity, to compare the degree of
      tortuosity in a series of consecutive patients with spontaneous CeAD and of age-
      and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) and
      stroke-free subjects. RESULTS: The study group was composed of 102 patients with
      CeAD (mean age, 44.5 +/- 7.8 years; 66.7% men), 102 with non-CEAD IS, and 102
      stroke-free subjects. The VTI was higher in the group of patients with CeAD
      (median, 7.3; 25th-75th percentile, 10.2) compared with that of non-CeAD IS
      (median, 3.4; 25th-75th percentile, 4.4) and of stroke-free subjects (median,
      4.0; 25th-75th percentile, 2.9; p <= 0.001), and was independently associated to
      the risk of CeAD (OR, 1.18; 95% CI, 1.09-1.29) in multivariable regression
      analysis. The degree of tortuosity also tended to be higher in CeAD patients who
      experienced short-term recurrence (5.8%; median, 20.2; 25th-75th percentile,
      31.2) than in those without recurrent events (median, 7.2; 25th-75th percentile,
      9.4; p = 0.074). CONCLUSION: CeAD patients exhibit increased arterial tortuosity.
      This might have potential implications for better understanding of the
      pathophysiology of the disease as well as clinical utility in evaluation,
      prognostication, and decision-making of affected individuals.

PMID- 28497263
TI  - Radiologic head CT interpretation errors in pediatric abusive and non-abusive
      head trauma patients.
AB  - BACKGROUND: Pediatric head trauma, including abusive head trauma, is a
      significant cause of morbidity and mortality. OBJECTIVE: The purpose of this
      research was to identify and evaluate radiologic interpretation errors of head
      CTs performed on abusive and non-abusive pediatric head trauma patients from a
      community setting referred for a secondary interpretation at a tertiary pediatric
      hospital. MATERIALS AND METHODS: A retrospective search identified 184 patients
      <5 years of age with head CT for known or potential head trauma who had a primary
      interpretation performed at a referring community hospital by a board-certified
      radiologist. Two board-certified fellowship-trained neuroradiologists at an
      academic pediatric hospital independently interpreted the head CTs, compared
      their interpretations to determine inter-reader discrepancy rates, and resolved
      discrepancies to establish a consensus second interpretation. The primary
      interpretation was compared to the consensus second interpretation using the
      RADPEERTM scoring system to determine the primary interpretation-second
      interpretation overall and major discrepancy rates. MRI and/or surgical findings
      were used to validate the primary interpretation or second interpretation when
      possible. The diagnosis of abusive head trauma was made using clinical and
      imaging data by a child abuse specialist to separate patients into abusive head
      trauma and non-abusive head trauma groups. Discrepancy rates were compared for
      both groups. Lastly, primary interpretations and second interpretations were
      evaluated for discussion of imaging findings concerning for abusive head trauma.
      RESULTS: There were statistically significant differences between primary
      interpretation-second interpretation versus inter-reader overall and major
      discrepancy rates (28% vs. 6%, P=0.0001; 16% vs. 1%, P=0.0001). There were
      significant differences in the primary interpretation-second interpretation
      overall and major discrepancy rates for abusive head trauma patients compared to
      non-abusive head trauma patients (41% vs 23%, P=0.02; 26% vs. 12%, P=0.03). The
      most common findings resulting in major radiologic interpretation errors were
      fractures and subdural hemorrhage. Differences in the age of the patient and the
      percentage of patients with hemorrhage were statistically significant between the
      abusive head trauma versus non-abusive head trauma groups, while no statistical
      difference was identified for skull fractures, ischemia, head CT radiation dose,
      or presence of multiplanar or 3-D reformatted images. The second interpretation
      more frequently indicated potential for abusive head trauma compared to the
      primary interpretation (P=0.0001). MRI and/or surgical findings were in agreement
      with the second interpretation in 29/29 (100%) of patients with discrepancies.
      CONCLUSION: A high incidence of radiologic interpretation errors may occur in
      pediatric trauma patients at risk for abusive head trauma who are referred from a
      community hospital. This suggests value for second interpretations of head CTs at
      a tertiary pediatric hospital for this patient population.

PMID- 28497264
TI  - Classification of parotidectomy: a proposed modification to the European Salivary
      Gland Society classification system.
AB  - Parotidectomy remains the mainstay of treatment for both benign and malignant
      lesions of the parotid gland. There exists a wide range of possible surgical
      options in parotidectomy in terms of extent of parotid tissue removed. There is
      increasing need for uniformity of terminology resulting from growing interest in
      modifications of the conventional parotidectomy. It is, therefore, of paramount
      importance for a standardized classification system in describing extent of
      parotidectomy. Recently, the European Salivary Gland Society (ESGS) proposed a
      novel classification system for parotidectomy. The aim of this study is to
      evaluate this system. A classification system proposed by the ESGS was critically
      re-evaluated and modified to increase its accuracy and its acceptability.
      Modifications mainly focused on subdividing Levels I and II into IA, IB, IIA, and
      IIB. From June 2006 to June 2016, 126 patients underwent 130 parotidectomies at
      our hospital. The classification system was tested in that cohort of patient.
      While the ESGS classification system is comprehensive, it does not cover all
      possibilities. The addition of Sublevels IA, IB, IIA, and IIB may help to address
      some of the clinical situations seen and is clinically relevant. We aim to test
      the modified classification system for partial parotidectomy to address some of
      the challenges mentioned.

PMID- 28497265
TI  - Proteomics analysis of pleomorphic adenoma of the human parotid gland.
AB  - : The objective of this study is to perform proteomic analysis of pleomorphic
      adenoma (PA) in the human parotid gland (PG) with comparison of normal PG. This
      is an individual prospective randomized controlled trial. This study was
      performed in a tertiary referral center. Tissue samples of PG and PA were taken
      after surgical excision of PG from 13 patients. Protein extracts were prepared
      and protein pools created from the soluble extracts were subjected to 2D-DIGE
      analysis. Proteins displaying regulation in their abundance were determined and
      identified using MALDIT-OF/TOF analysis. The identified proteins were subjected
      to STRING analysis for classification of the proteins based on their biological
      roles in metabolic pathways. Fifteen proteins, carbonic anhydrase 1, carbonic
      anhydrase 2, fibrinogen beta chain, alpha-amylase 1, heats hock protein hsp 90
      alpha, clusterin, 78 kDa glucose-regulated protein, endoplasmin, alpha-amylase
      2b, ATP synthase subunit alpha (mitochondrial), elongation factor 1-gamma, malate
      dehydrogenase, cytoplasmic, triosephosphate isomerase, receptor of activated
      protein c kinase 1, and aconitate hydratase, mitochondrial were down-regulated,
      whereas 11 proteins including ig kappa chain c region, serotransferrin, vimentin,
      annexin a5, glial fibrillary acidic protein, calreticulin, cartilage oligomeric
      matrix protein, microfibril-associated glycoprotein 4, 14-3-3 protein epsilon,
      fibulin-5, and f-box only protein 2 were up-regulated in PA samples in comparison
      to healthy parotid tissue. This study described the differences observed in
      protein expression patterns of the PA and normal PG. The results may provide new
      insights into the pathogenesis and diagnosis of PA in human PG. LEVEL OF
      EVIDENCE: 1b.

PMID- 28497266
TI  - An insecticidal toxin from Nephila clavata spider venom.
AB  - Spiders are the most successful insect predators given that they use their venom
      containing insecticidal peptides as biochemical weapons for preying. Due to the
      high specificity and potency of peptidic toxins, discoveries of insecticidal
      toxins from spider venom have provided an opportunity to obtain natural compounds
      for agricultural applications without affecting human health. In this study, a
      novel insecticidal toxin (MU-NPTX-Nc1a) was identified and characterized from the
      venom of Nephila clavata. Its primary sequence is
      GCNPDCTGIQCGWPRCPGGQNPVMDKCVSCCPFCPPKSAQG which was determined by automated Edman
      degradation, cDNA cloning, and MS/MS analysis. BLAST search indicated that Nc1a
      shows no similarity with known peptides or proteins, indicating that Nc1a belongs
      to a novel family of insecticidal peptide. Nc1a displayed inhibitory effects on
      NaV and KV channels in cockroach dorsal unpaired median neurons. The median
      lethal dose (LD50) of Nc1a on cockroach was 573 ng/g. Herein, a study that
      identifies a novel insecticidal toxin, which can be a potential candidate and/or
      template for the development of bioinsecticides, is presented.

PMID- 28497267
TI  - Understanding blood gas analysis.

PMID- 28497268
TI  - Pulmonary embolism following severe traumatic brain injury: incidence, risk
      factors and impact outcome.

PMID- 28497269
TI  - On the verge of using an immune toolbox in the intensive care unit?

PMID- 28497270
TI  - The dynamic arterial elastance: a call for a cautious interpretation : Discussion
      on "Predicting vasopressor needs using dynamic parameters".

PMID- 28497271
TI  - Super-refractory status epilepticus: epidemiology, early predictors, and
      outcomes.

PMID- 28497272
TI  - Selective decontamination of the digestive tract halves the prevalence of
      ventilator-associated pneumonia compared to selective oral decontamination.

PMID- 28497273
TI  - CCCS-SSAI WikiRecs clinical practice guideline: vasopressor blood pressure
      targets in critically ill adults with hypotension and vasopressor use in early
      traumatic shock.

PMID- 28497274
TI  - Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome.
AB  - Megalin (or LRP2) is an endocytic receptor that plays a central role in embryonic
      development and adult tissue homeostasis. Loss of this receptor in congenital or
      acquired diseases results in multiple organ dysfunctions, including forebrain
      malformation (holoprosencephaly) and renal reabsorption defects (renal Fanconi
      syndrome). Here, we describe current concepts of the mode of receptor action that
      include co-receptors and a repertoire of different ligands, and we discuss how
      these interactions govern functional integrity of the kidney and the brain, and
      cause disease when defective.

PMID- 28497275
TI  - Na +/Ca2+ exchangers and Orai channels jointly refill endoplasmic reticulum (ER)
      Ca2+ via ER nanojunctions in vascular endothelial cells.
AB  - We investigated the role of Na+/ Ca2+ exchange (NCX) in the refilling of
      endoplasmic reticulum (ER) Ca2+ in vascular endothelial cells under various
      conditions of cell stimulation and plasma membrane (PM) polarization. Better
      understanding of the mechanisms behind basic ER Ca2+ content regulation is
      important, since current hypotheses on the possible ultimate causes of ER stress
      point to deterioration of the Ca2+ transport mechanism to/from ER itself. We
      measured [Ca2+]i temporal changes by Fura-2 fluorescence under experimental
      protocols that inhibit a host of transporters (NCX, Orai, non-selective transient
      receptor potential canonical (TRPC) channels, sarco/endoplasmic reticulum Ca2+
      ATPase (SERCA), Na+/ K+ ATPase (NKA)) involved in the Ca2+ communication between
      the extracellular space and the ER. Following histamine-stimulated ER Ca2+
      release, blockade of NCX Ca2+-influx mode (by 10 MUM KB-R7943) diminished the ER
      refilling capacity by about 40%, while in Orai1 dominant negative-transfected
      cells NCX blockade attenuated ER refilling by about 60%. Conversely, inhibiting
      the ouabain sensitive NKA (10 nM ouabain), which may be localized in PM-ER
      junctions, increased the ER Ca2+ releasable fraction by about 20%, thereby
      supporting the hypothesis that this process of privileged ER refilling is
      junction-mediated. Junctions were observed in the cell ultrastructure and their
      main parameters of membrane separation and linear extension were (9.6 +/- 3.8) nm
      and (128 +/- 63) nm, respectively. Our findings point to a process of privileged
      refilling of the ER, in which NCX and store-operated Ca2+ entry via the stromal
      interaction molecule (STIM)-Orai system are the sole protagonists. These results
      shed light on the molecular machinery involved in the function of a previously
      hypothesized subplasmalemmal Ca2+ control unit during ER refilling with
      extracellular Ca2+.

PMID- 28497276
TI  - Thermal perception thresholds among workers in a cold climate.
AB  - PURPOSE: To investigate whether exposure to cold could influence the thermal
      perception thresholds in a working population. METHODS: This cross-sectional
      study was comprised of 251 males and females and was carried out at two mines in
      the northern part of Norway and Sweden. The testing included a baseline
      questionnaire, a clinical examination and measurements of thermal perception
      thresholds, on both hands, the index (Digit 2) and little (Digit 5) fingers, for
      heat and cold. RESULTS: The thermal perception thresholds were affected by age,
      gender and test site. The thresholds were impaired by experiences of frostbite in
      the fingers and the use of medication that potentially could affect neurosensory
      functions. No differences were found between the calculated normative values for
      these workers and those in other comparative investigations conducted in warmer
      climates. CONCLUSIONS: The study provided no support for the hypothesis that
      living and working in cold climate will lead to impaired thermal perception
      thresholds. Exposure to cold that had caused localized damage in the form of
      frostbite was shown to lead to impaired thermal perception.

PMID- 28497277
TI  - Brazilin Ameliorates Diabetic Nephropathy and Inflammation in db/db Mice.
AB  - Hyperglycemia and inflammation play important roles in the pathogenesis of
      diabetic nephropathy (DN). Brazilin might be an effective pharmacological agent
      against hyperglycemia and inflammation. In our present study, we explored whether
      brazilin mitigated pathological progression, inflammation, and extracellular
      matrix (ECM) accumulation in a mouse model of diabetic nephropathy. Brazilin
      reduced aggravated biochemical indices of DN (proteinuria and the serum glucose
      level) and renal hypertrophy. Brazilin also improved renal morphology and
      inhibited macrophage infiltration, as manifested by different pathological
      staining methods. Brazilin reduced the levels of pro-inflammatory cytokines and
      CD68, a macrophage marker, in the kidney cortex, as revealed by both RT-PCR and
      western blotting experiments. Furthermore, brazilin significantly downregulated
      the serum levels of pro-inflammatory cytokines and chemokines. Interestingly,
      brazilin significantly upregulated the levels of the anti-inflammatory factor IL
      10, and prevented ECM accumulation. Brazilin reduced nuclear translocation of the
      NF-kappaB p65 subunit both in vitro and in vivo. Thus, brazilin might be a useful
      treatment for DN, through mitigating hypoglycemia, inflammation, and ECM
      accumulation.

PMID- 28497278
TI  - IL-35 Pretreatment Alleviates Lipopolysaccharide-Induced Acute Kidney Injury in
      Mice by Inhibiting NF-kappaB Activation.
AB  - Septic acute kidney injury (AKI) is a public health problem with high mortality.
      Suppression of over-active inflammation is considered as a promising strategy for
      septic AKI. In this study, we evaluated the prophylactic effect of interleukin
      (IL)-35, the unique immune-suppressive member of IL-12 cytokine family, on
      lipopolysaccharide (LPS)-induced AKI in mice, and found that compared with
      control mice given empty vector, mice pretreated with plasmid encoding IL-35 (pIL
      35) significantly improved renal function indicated by reduced blood urea
      nitrogen (BUN) and serum creatinine (SCr), and obviously alleviated renal
      pathological changes. To explore the underlying protective mechanisms, we found
      that pIL-35 treatment could robustly reduce the production of renal pro
      inflammatory cytokines (TNF-alpha, IL-6, and IL-1beta), with no significant
      impact on IL-10, an anti-inflammatory cytokine. Furthermore, our results revealed
      that IL-35 pretreatment could potentially inhibit the activation of renal NF
      kappaB signaling pathway in LPS-induced AKI mice. Taken together, our study
      indicated that IL-35 pretreatment could efficiently prevent LPS-induced AKI via
      inhibiting NF-kappaB activation and reducing pro-inflammatory cytokine
      production, and it might represent a novel therapeutic strategy against septic
      AKI and other inflammatory renal diseases.

PMID- 28497279
TI  - Aspiring to have the looks of a celebrity: young girls' engagement in appearance
      management behaviors.
AB  - : Research suggests that sexualizing media messages are present in teen media and
      negatively affect young girls' body image. Yet, it is unknown whether exposure to
      teen television programs is associated with girls' engagement in appearance
      management behaviors. Two-wave longitudinal data among 785 girls (Mage = 11.65
      years) were collected. Results show that teen television exposure was
      longitudinally related to appearance management, while the reverse relation was
      not supported. Approximately half of the girls indicated to manage their
      appearance to some extent, and 13- to 14-year-old girls were more likely to
      invest in their appearance than younger girls. Thirty percent of those who did
      not manage their appearance at the start of the study indicated to have initiated
      appearance management 6 months later. Frequent viewers were four times, three
      times, and twice as more likely to style their hair, wear heels, and apply make
      up compared to non-viewers. CONCLUSION: The current study showed that teen media
      exposure plays a role in young girls' appearance management. The findings point
      to a need to teach young girls about stereotypical messages in media content
      directed towards them. Prevention efforts should focus on girls who frequently
      watch teen media. What is Known: * Sexualizing media messages are present in teen
      media. * Gender identity development is one of the key tasks during adolescence.
      What is New: * Tween television exposure predicts 9- to 14-year-old girls'
      engagement in appearance management over time. * Engagement in appearance
      management behaviors did not predict 9- to 14-year-old girls' exposure to tween
      television programs.

PMID- 28497280
TI  - A minimal soft tissue damage approach of spondylolysis repair in athletes:
      preliminary report.
AB  - PURPOSE AND HYPOTHESIS: Both spondylolysis and spondylolisthesis come in second
      place in the causes of pain among athletes. Treatment options include both
      conservative management and different operative methods. Athletes and adolescents
      are groups where the priority is to protect tissues from perioperative damage.
      OBJECTIVE: We present our modification of the Buck's, direct pars repair method,
      which we believe offers maximum protection of tissues. We used the modified
      surgical method in young, competitive athletes, in whom non-surgical treatment
      was not effective. METHOD: Eight pars defects in five patients were treated using
      suggested method. All of them were young males (aged between 13 and 18 years),
      who practice soccer professionally. We use modified method of direct repair pars
      through the cannulated screw fixation, first proposed by Buck. Preoperative
      preparation consists of proper analysis of computer tomography images in
      multiplanar reconstruction mode: measuring screw length, measurement of
      inclination angle of the optimal screw trajectory in the frontal and sagittal
      plane. During the operation, the wire proper direction is performed by usage of
      the predetermined angles. Starting point for guide wire was also changed to the
      lower end of the facet. The fusion takes place with a screw of 3 mm diameter.
      After the operation patient need to use thoracolumbar spinal orthosis as a
      primary immobilization for 6 weeks and appropriate rehabilitation for another 6
      weeks. We used these methods in eight pars fixations. RESULTS: All of the
      patients were painless in first week after surgery. All of them underwent total
      rehabilitation programme and returned to sport. CONCLUSIONS: Direct pars repair
      using Buck's method with proposed modification, including adequate radiographic
      preparation, the use of a thin cannulated screw and changing the point of screw
      entry, allows precise and safe screw placement, regardless of the size of the
      bone at the defect site.

PMID- 28497281
TI  - Preoperative chest radiographs in hip fracture patients: is there any additional
      value?
AB  - PURPOSE: Preoperative screening in hip fracture patients is vital to minimize
      perioperative complications. Preoperative chest radiographs (POCR) are performed
      in many hip fracture patients. Earlier research showed that few POCR
      abnormalities influence perioperative policy. However, no studies in nonelective
      patient with a specific surgical conditions have been performed. With many hip
      fractures per year worldwide, a significant cost reduction could be made by
      performing selective POCR without compromising the quality of care. This study
      assessed the need for POCR in hip fracture patients. METHOD: Retrospective
      analysis of low-energy trauma patients was performed aged 18 years and older in
      the VU University Medical Center for a hip fracture in a 5-year period. All
      preoperative diagnostics were analyzed. All adjourned operations were evaluated.
      RESULTS: A total of 642 patients were included, 70% female, matching current
      epidemiologic figures. The POCR showed abnormalities in 22.6%. In 0.6% the POCR
      lead to an adjournment of the operation (2.8% of abnormal POCR's). These patients
      suffered from pneumonia. The POCR in these cases acted as a confirmation of the
      clinical diagnosis. CONCLUSION: Many factors involving the treatment of hip
      fracture patients are of importance in minimizing the risk of complications and
      mortality during and after admission. In 0.6% of all performed POCR's an
      abnormality leads to the adjournment of the operation. In all four cases the POCR
      matched the clinical findings. Because the additional value of the POCR in hip
      fracture patients was limited, we think that its selective use in clinical
      abnormalities is safe and will reduce unnecessary costs.

PMID- 28497282
TI  - Highly complex substrates lead to dynamic bacterial community for
      polyhydroxyalkanoates production.
AB  - Mixed microbial cultures (MMC) and waste/surplus substrates, as hardwood spent
      sulfite liquor, are being used to decrease polyhydroxyalkanoates' (PHA)
      production costs. The process involves two or three steps, being the selection
      step a crucial one. For the industrial implementation of this strategy, reactor
      stability in terms of both performance and microbial community presence has to be
      considered. A long-term operation of a sequencing batch reactor under
      feast/famine conditions was performed along with microbial community
      identification/quantification using FISH and DGGE. The community was found to be
      extremely dynamic, dominated by Alphaproteobacteria, with Paracoccus and
      Rhodobacter present, both PHA-storing microorganisms. 16S rRNA gene clone library
      further revealed that side populations' non-PHA accumulators were able to strive
      (Agrobacterium, Flavobacteria, and Brachymonas). Nevertheless, reactor
      performance in terms of PHA storage was stable during operation time. The
      monitoring of the MMC population evolution provided information on the relation
      between community structure and process operation.

PMID- 28497283
TI  - The Impact of Resistance Training on Swimming Performance: A Systematic Review.
AB  - BACKGROUND: The majority of propulsive forces in swimming are produced from the
      upper body, with strong correlations between upper body strength and sprint
      performance. There are significant gaps in the literature relating to the impact
      of resistance training on swimming performance, specifically the transfer to
      swimming performance. OBJECTIVE: The aims of this systematic literature review
      are to (1) explore the transfer of resistance-training modalities to swimming
      performance, and (2) examine the effects of resistance training on technical
      aspects of swimming. METHODS: Four online databases were searched with the
      following inclusion criteria: (1) journal articles with outcome measures related
      to swimming performance, and (2) competitive swimmers participating in a
      structured resistance-training programme. Exclusion criteria were (1)
      participants with a mean age <16 years; (2) untrained, novice, masters and
      paraplegic swimmers; (3) triathletes and waterpolo players; (4) swimmers with
      injuries or illness; and (5) studies of starts and turns specifically. Data were
      extracted using the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines, and the Physiotherapy Evidence Database (PEDro)
      scale was applied. RESULTS: For optimal transfer, specific, low-volume, high
      velocity/force resistance-training programmes are optimal. Stroke length is best
      achieved through resistance training with low repetitions at a high
      velocity/force. Resisted swims are the most appropriate training modality for
      improving stroke rate. CONCLUSION: Future research is needed with respect to the
      effects of long-term resistance-training interventions on both technical
      parameters of swimming and overall swimming performance. The results of such work
      will be highly informative for the scientific community, coaches and athletes.

PMID- 28497284
TI  - Exercise Interventions for the Prevention and Treatment of Groin Pain and Injury
      in Athletes: A Critical and Systematic Review.
AB  - BACKGROUND: Groin injury is a common musculoskeletal complaint for athletes
      competing in a variety of sports. The extent to which exercise interventions
      incorporating external load are an appropriate option for the treatment and
      prevention of groin injury in athletes is not yet clear. OBJECTIVES: The aim of
      this review was to describe and evaluate exercise therapy interventions and
      outcomes for the treatment and prevention of groin injury with specific attention
      to application of external load. DATA SOURCES: The databases Medline, PubMed,
      SPORTDiscus, Web of Science, and Cochrane were searched on 18 April 2016. STUDY
      ELIGIBILITY CRITERIA: This review was registered as PROSPERO CRD42016037752 and a
      systematic search was conducted with the following inclusion criteria: any study
      design evaluating exercise interventions for the prevention or treatment of groin
      pain in athletes. DATA ANALYSIS: Two independent authors screened search results,
      performed data extraction, assessed risk of bias using the modified Downs and
      Black appraisal tool and determined strength and level of evidence. Reporting
      standards for exercise interventions were assessed using the Consensus for
      Exercise Reporting Template (CERT). RESULTS: A total of 1320 titles were
      identified with 14 studies satisfying the inclusion criteria, four (29%) of which
      demonstrated low risk of bias. Ten (71%) studies utilised external load as a
      component of the exercise intervention. Reporting standards for exercise
      intervention scores ranged from 0 to 63%. CONCLUSION: There is limited evidence
      from level 2 and 3 studies indicating exercise therapy may reduce the incidence
      and hazard risk of sustaining a groin injury in athletes. There is strong
      evidence from level 4 studies indicating exercise therapy is beneficial as a
      treatment for groin injury in athletes in terms of symptom remission, return to
      sport and recurrence outcomes. However, there are limited studies with low risk
      of bias, and exercise interventions for the treatment of groin injury are poorly
      described.

PMID- 28497285
TI  - Comparison of Periodized and Non-Periodized Resistance Training on Maximal
      Strength: A Meta-Analysis.
AB  - BACKGROUND: Periodization is a logical method of organizing training into
      sequential phases and cyclical time periods in order to increase the potential
      for achieving specific performance goals while minimizing the potential for
      overtraining. Periodized resistance training plans are proposed to be superior to
      non-periodized training plans for enhancing maximal strength. OBJECTIVE: The
      primary aim of this study was to examine the previous literature comparing
      periodized resistance training plans to non-periodized resistance training plans
      and determine a quantitative estimate of effect on maximal strength. METHODS: All
      studies included in the meta-analysis met the following inclusion criteria: (1)
      peer-reviewed publication; (2) published in English; (3) comparison of a
      periodized resistance training group to a non-periodized resistance training
      group; (4) maximal strength measured by 1-repetition maximum (1RM) squat, bench
      press, or leg press. Data were extracted and independently coded by two authors.
      Random-effects models were used to aggregate a mean effect size (ES), 95%
      confidence intervals (CIs) and potential moderators. RESULTS: The cumulative
      results of 81 effects gathered from 18 studies published between 1988 and 2015
      indicated that the magnitude of improvement in 1RM following periodized
      resistance training was greater than non-periodized resistance training (ES =
      0.43, 95% CI 0.27-0.58; P < 0.001). Periodization model (beta = 0.51; P =
      0.0010), training status (beta = -0.59; P = 0.0305), study length (beta = 0.03; P
      = 0.0067), and training frequency (beta = 0.46; P = 0.0123) were associated with
      a change in 1RM. These results indicate that undulating programs were more
      favorable for strength gains. Improvements in 1RM were greater among untrained
      participants. Additionally, higher training frequency and longer study length
      were associated with larger improvements in 1RM. CONCLUSION: These results
      suggest that periodized resistance training plans have a moderate effect on 1RM
      compared to non-periodized training plans. Variation in training stimuli appears
      to be vital for increasing maximal strength, and longer periods of higher
      training frequency may be preferred.

PMID- 28497286
TI  - The Influence of Drinking Fluid on Endurance Cycling Performance: A Meta
      Analysis.
AB  - BACKGROUND: Fluid replacement during cycling exercise evolves on a spectrum from
      simply drinking to thirst to planned structured intake, with both being
      appropriate recommendations. However, with mixed findings suggesting fluid intake
      may or may not improve endurance cycling performance (ECP) in a diverse range of
      trained individuals, there is a clear need for summarised evidence regarding the
      effect of fluid consumption on ECP. OBJECTIVES: (1) Determine the magnitude of
      the effect of drinking fluid on performance during cycling exercise tasks of
      various durations, compared with no drinking; (2) examine the relationship
      between rates of fluid intake and ECP; and (3) establish fluid intake
      recommendations based on the observations between rates of fluid intake and ECP.
      STUDY DESIGN: Meta-analysis. METHODS: Studies were located via database searches
      and cross-referencing. Performance outcomes were converted to a similar metric to
      represent percentage change in power output. Fixed- and random-effects weighted
      mean effect summaries and meta-regression analyses were used to identify the
      impact of drinking fluid on ECP. RESULTS: A limited number of research
      manuscripts (n = 9) met the inclusion criteria, producing 15 effect estimates.
      Meta-regression analyses demonstrated that the impact of drinking on ECP under 20
      33  degrees C ambient temperatures was duration-dependent. Fluid consumption of,
      on average, 0.29 mL/kg body mass/min impaired 1 h high-intensity (80% peak oxygen
      uptake [[Formula: see text]o2peak]) ECP by -2.5 +/- 0.8% (95% confidence interval
      [CI] -4.1 to -0.9%) compared with no fluid ingestion. In contrast, during >1 to
      <=2 h and >2 h moderate-intensity (60-70% [Formula: see text]o2peak) cycling
      exercise, ECP improved by 2.1 +/- 1.5% (95% CI 1.2-2.9%) and 3.2 +/- 1.2% (95% CI
      0.8-5.6%), respectively, with fluid ingestion compared with no fluid intake. The
      associated performance benefits were observed when the rates of fluid intake were
      in the range of 0.15-0.20 mL/kg body mass/min for >1 to <=2 h cycling exercise
      and ad libitum or 0.14-0.27 mL/kg body mass/min for cycling exercise >2 h.
      CONCLUSIONS: A rate of fluid consumption of between 0.15 and 0.34 mL/kg body
      mass/min during high-intensity 1 h cycling exercise is associated with reductions
      in ECP. When cycling at moderate intensity for >1 to <=2 h, cyclists should
      expect a gain in performance of at least 2% if fluid is consumed at a rate of
      0.15-0.20 mL/kg body mass/min. For cycling exercise >2 h conducted at moderate
      intensity, consuming fluid ad libitum or at a rate of 0.14-0.27 mL/kg body
      mass/min should improve performance by at least 3%. Until further research is
      conducted, these recommendations should be used as a guide to inform hydration
      practices.

PMID- 28497287
TI  - Role of nitrite in the competition between denitrification and DNRA in a
      chemostat enrichment culture.
AB  - Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two
      microbial processes that compete for oxidized nitrogen compounds in the
      environment. The objective of this work was to determine the role of nitrite
      versus nitrate as terminal electron acceptor on the competition between DNRA and
      denitrification. Initially, a mixed culture chemostat was operated under nitrate
      limitation and performed DNRA. Stepwise, the influent nitrate was replaced with
      nitrite until nitrite was the sole electron acceptor and N-source present.
      Despite changing the electron acceptor from nitrate to nitrite, the dominant
      process remained DNRA and the same dominant organism closely related to Geobacter
      lovleyi was identified. Contrary to previous studies conducted with a complex
      substrate in marine microbial communities, the conclusion of this work is that
      nitrate versus nitrite as electron acceptor does not generally control the
      competition between DNRA and denitrification. Our results show that the effect of
      this ratio must be interpreted in combination with other environmental factors,
      such as the type and complexity of the electron donor, pH, or sulfide
      concentrations.

PMID- 28497288
TI  - Novel signal peptides improve the secretion of recombinant Staphylococcus aureus
      Alpha toxinH35L in Escherichia coli.
AB  - Secretion of heterologous proteins into Escherichia coli cell culture medium
      offers significant advantages for downstream processing over production as
      inclusion bodies; including cost and time savings, and reduction of endotoxin.
      Signal peptides play an important role in targeting proteins for translocation
      across the cytoplasmic membrane to the periplasmic space and release into culture
      medium during the secretion process. Alpha toxinH35L (ATH35L) was selected as an
      antigen for vaccine development against Staphylococcus aureus infections. It was
      successfully secreted into culture medium of E. coli by using bacterial signal
      peptides linked to the N-terminus of the protein. In order to improve the level
      of secreted ATH35L, we designed a series of novel signal peptides by swapping
      individual domains of modifying dsbA and pelB signal peptides and tested them in
      a fed-batch fermentation process. The data showed that some of the modified
      signal peptides improved the secretion efficiency of ATH35L compared with E. coli
      signal peptides from dsbA, pelB and phoA proteins. Indeed, one of the novel
      signal peptides improved the yield of secreted ATH35L by 3.5-fold in a fed-batch
      fermentation process and at the same time maintained processing at the expected
      site for signal peptide cleavage. Potentially, these new novel signal peptides
      can be used to improve the secretion efficiency of other heterologous proteins in
      E. coli. Furthermore, analysis of the synthetic signal peptide amino acid
      sequences provides some insight into the sequence features within the signal
      peptide that influence secretion efficiency.

PMID- 28497289
TI  - Systematic analysis of the lysine acetylome reveals diverse functions of lysine
      acetylation in the oleaginous yeast Yarrowia lipolytica.
AB  - Lysine acetylation of proteins, a major post-translational modification, plays a
      critical regulatory role in almost every aspects in both eukaryotes and
      prokaryotes. Yarrowia lipolytica, an oleaginous yeast, is considered as a model
      for bio-oil production due to its ability to accumulate a large amount of lipids.
      However, the function of lysine acetylation in this organism is elusive. Here, we
      performed a global acetylproteome analysis of Y. lipolytica ACA-DC 50109. In
      total, 3163 lysine acetylation sites were identified in 1428 proteins, which
      account for 22.1% of the total proteins in the cell. Fifteen conserved
      acetylation motifs were detected. The acetylated proteins participate in a wide
      variety of biological processes. Notably, a total of 65 enzymes involved in lipid
      biosynthesis were found to be acetylated. The acetylation sites are distributed
      in almost every type of conserved domains in the multi-enzymatic complexes of
      fatty acid synthetases. The provided dataset probably illuminates the crucial
      role of reversible acetylation in oleaginous microorganisms, and serves as an
      important resource for exploring the physiological role of lysine acetylation in
      eukaryotes.

PMID- 28497290
TI  - Medium-chain-length polyhydroxyalkanoates synthesis by Pseudomonas putida KT2440
      relA/spoT mutant: bioprocess characterization and transcriptome analysis.
AB  - Pseudomonas putida KT2440 is a model bacteria used commonly for medium-chain
      length polyhydroxyalkanoates (mcl-PHAs) production using various substrates.
      However, despite many studies conducted on P. putida KT2440 strain, the molecular
      mechanisms of leading to mcl-PHAs synthesis in reaction to environmental stimuli
      are still not clear. The rearrangement of the metabolism in response to
      environmental stress could be controlled by stringent response that modulates the
      transcription of many genes in order to promote survival under nutritional
      deprivation conditions. Therefore, in this work we investigated the relation
      between mcl-PHAs synthesis and stringent response. For this study, a relA/spoT
      mutant of P. putida KT2440, unable to induce the stringent response, was used.
      Additionally, the transcriptome of this mutant was analyzed using RNA-seq in
      order to examine rearrangements of the metabolism during cultivation. The results
      show that the relA/spoT mutant of P. putida KT2440 is able to accumulate mcl-PHAs
      in both optimal and nitrogen limiting conditions. Nitrogen starvation did not
      change the efficiency of mcl-PHAs synthesis in this mutant. The transition from
      exponential growth to stationary phase caused significant upregulation of genes
      involved in transport system and nitrogen metabolism. Transcriptional regulators,
      including rpoS, rpoN and rpoD, did not show changes in transcript abundance when
      entering the stationary phase, suggesting their limited role in mcl-PHAs
      accumulation during stationary phase.

PMID- 28497291
TI  - Two early eudicot fossil flowers from the Kamikitaba assemblage (Coniacian, Late
      Cretaceous) in northeastern Japan.
AB  - Two new fossil taxa referable to the basal eudicot grade are described from the
      Kamikitaba locality (ca. 89 MYBP, early Coniacian: Late Cretaceous) of the Futaba
      Group in Japan. These charcoalified mesofossils exhibit well-preserved three
      dimensional structure and were analyzed using synchrotron-radiation X-ray
      microtomography to document their composition and internal structure. Cathiaria
      japonica sp. nov. is represented by infructescence segments that consist of an
      axis bearing three to four fruits. The capsular fruits are sessile and dehiscent
      and consist of a gynoecium subtended by a bract. No perianth parts are present.
      The gynoecium is monocarpellate containing two pendulous seeds. The carpel is
      ascidiate in the lower half and conduplicate in the upper part, and the style is
      deflected abaxially with a large, obliquely decurrent stigma. Pollen grains are
      tricolpate with a reticulate exine. The morphological features of Cathiaria are
      consistent with an assignment to the Buxaceae s. l. (including Didymelaceae).
      Archaestella verticillatus gen. et sp. nov. is represented by flowers that are
      small, actinomorphic, pedicellate, bisexual, semi-inferior, and multicarpellate.
      The floral receptacle is cup shaped with a perigynous perianth consisting of
      several tepals inserted around the rim. The gynoecium consists of a whorl of ten
      conduplicate, laterally connate but distally distinct carpels with a conspicuous
      dorsal bulge, including a central cavity. The styles are short, becoming recurved
      with a ventrally decurrent stigma. Seeds are ca. 10 per carpel, marginal,
      pendulous from the broad, oblique summit of the locule. Pollen grains are
      tricolpate with a reticulate exine pattern, suggesting a relationship to
      eudicots. The morphological features of Archaestella indicate a possible
      relationship to Trochodendraceae in the basal grade of eudicots. The fossil
      currently provides the earliest record of the family and documents the presence
      of Trochodendraceae in eastern Eurasia during the middle part of the Late
      Cretaceous.

PMID- 28497292
TI  - Cancer subtypes in aetiological research.
AB  - Researchers often attempt to categorize tumors into more homogeneous subtypes to
      better predict prognosis or understand pathogenic mechanisms. In clinical
      research, typically the focus is on prognosis: the tumor subtypes are intended to
      be associated with specific responses to treatment and/or different clinical
      outcomes. In aetiological research, the focus is on identifying distinct
      pathogenic mechanisms, which may involve different risk factors. We used directed
      acyclic graphs to present a framework for considering potential biases arising in
      aetiological research of tumor subtypes, when there is incomplete correspondence
      between the identified subtypes and the underlying pathogenic mechanisms. We
      identified two main scenarios: (1) weak effect, when the tumor subtypes are
      identified through combinations of characteristics and some of these
      characteristics are affected by factors that are unrelated with the underlying
      pathogenic mechanisms; and (2) lack of causality, when the set of characteristics
      corresponds with a mechanism that is actually not a cause of the tumor of
      interest. Examples of the magnitude of bias that can be introduced in these
      situations are provided. Although categorization of tumors into homogenous
      subtypes may have important implications for aetiological research and
      identification of risk factors, the characteristics used to classify tumors into
      subtypes should be as close as possible to the actual pathogenic mechanisms to
      avoid interpretative biases. Whenever our knowledge of these mechanisms is
      limited, research into risk factors for tumor subtypes should first aim to
      causally link the characteristics to the pathogenic mechanisms.

PMID- 28497293
TI  - Calcium Oscillation Frequency-Sensitive Gene Regulation and Homeostatic
      Compensation in Pancreatic beta-Cells.
AB  - Pancreatic islet [Formula: see text]-cells are electrically excitable cells that
      secrete insulin in an oscillatory fashion when the blood glucose concentration is
      at a stimulatory level. Insulin oscillations are the result of cytosolic
      [Formula: see text] oscillations that accompany bursting electrical activity of
      [Formula: see text]-cells and are physiologically important. ATP-sensitive
      [Formula: see text] channels (K(ATP) channels) play the key role in setting the
      overall activity of the cell and in driving bursting, by coupling cell metabolism
      to the membrane potential. In humans, when there is a defect in K(ATP) channel
      function, [Formula: see text]-cells fail to respond appropriately to changes in
      the blood glucose level, and electrical and [Formula: see text] oscillations are
      lost. However, mice compensate for K(ATP) channel defects in islet [Formula: see
      text]-cells by employing alternative mechanisms to maintain electrical and
      [Formula: see text] oscillations. In a recent study, we showed that in mice
      islets in which K(ATP) channels are genetically knocked out another [Formula: see
      text] current, provided by inward-rectifying [Formula: see text] channels, is
      increased. With mathematical modeling, we demonstrated that a sufficient
      upregulation in these channels can account for the paradoxical electrical
      bursting and [Formula: see text] oscillations observed in these [Formula: see
      text]-cells. However, the question of determining the correct level of
      upregulation that is necessary for this compensation remained unanswered, and
      this question motivates the current study. [Formula: see text] is a well-known
      regulator of gene expression, and several examples have been shown of genes that
      are sensitive to the frequency of the [Formula: see text] signal. In this
      mathematical modeling study, we demonstrate that a [Formula: see text]
      oscillation frequency-sensitive gene transcription network can adjust the gene
      expression level of a compensating [Formula: see text] channel so as to rescue
      electrical bursting and [Formula: see text] oscillations in a model [Formula: see
      text]-cell in which the key K(ATP) current is removed. This is done without the
      prescription of a target [Formula: see text] level, but evolves naturally as a
      consequence of the feedback between the [Formula: see text]-dependent enzymes and
      the cell's electrical activity. More generally, the study indicates how [Formula:
      see text] can provide the link between gene expression and cellular electrical
      activity that promotes wild-type behavior in a cell following gene knockout.

PMID- 28497294
TI  - A two-step deconvolution-analysis-informed population pharmacodynamic modeling
      approach for drugs targeting pulsatile endogenous compounds.
AB  - Pharmacodynamic modeling of pulsatile endogenous compounds (e.g. growth hormone
      [GH]) is currently limited to the identification of a low number of pulses.
      Commonly used pharmacodynamic models are not able to capture the complexity of
      pulsatile secretion and therefore non-compartmental analyses are performed to
      extract summary statistics (mean, AUC, Cmax). The aim of this study was to
      develop a new quantification method that deals with highly variable pulsatile
      data by using a deconvolution-analysis-informed population pharmacodynamic
      modeling approach. Pulse frequency and pulse times were obtained by deconvolution
      analysis of 24 h GH profiles. The estimated pulse times then informed a non
      linear mixed effects population pharmacodynamic model in NONMEM V7.3. The
      population parameter estimates were used to perform simulations that show
      agonistic and antagonistic drug effects on the secretion of GH. Additionally, a
      clinical trial simulation shows the application of this method in the
      quantification of a hypothetical drug effect that inhibits GH secretion. The GH
      profiles were modeled using a turnover compartment in which the baseline
      secretion, kout, pulse secretion width, amount at time point 0 and pulse
      amplitude were estimated as population parameters. Population parameters were
      estimated with low relative standard errors (ranging from 2 to 5%). Total body
      water (%) was identified as a covariate for pulse amplitude, baseline secretion
      and the pulse secretion width following a power relationship. Simulations
      visualized multiple gradients of a hypothetical drug that influenced the
      endogenous secretion of GH. The established model was able to fit and quantify
      the highly variable individual 24 h GH profiles over time. This pharmacodynamic
      model can be used to quantify drug effects that target other endogenous pulsatile
      compounds.

PMID- 28497295
TI  - Assessing the risk and disease burden of Clostridium difficile infection among
      patients with hospital-acquired pneumonia at a University Hospital in Central
      China.
AB  - PURPOSE: Hospital-acquired pneumonia (HAP) remains one of the major hospital
      acquired infections in China. Antibiotic treatment of HAP may lead to subsequent
      Clostridium difficile infection (CDI). Baseline data on the occurrence of CDI
      among HAP patients in China are currently unavailable. This study examines the
      risk and disease burden of CDI among HAP hospitalized patients (HAP-CDI).
      METHODS: We conducted a prospective study among ICU patients with HAP and
      hospital-onset diarrhea from January 2014 to December 2014 in a teaching hospital
      in China. All stool specimens were cultured for C. difficile which were typed by
      MLST. We used univariate and multivariable regression analyses to identify risk
      factors of HAP-CDI. FINDINGS: In total, 369 patients who met the inclusion
      criteria were enrolled. Thirty-two patients tested C. difficile positive. Among
      the isolated C. difficile strains, 90.63% (29/32) isolates were toxinogenic.
      Various MLST types were identified. The incidence of HAP-CDI was 11.67/10,000
      patient days (95% CI, 7.97-16.55). Nineteen patients died from complications. The
      attributable mortality rate was 5.15% (19/369). The mortality rate of HAP-CDI
      group was 13.79% which was higher than HAP-non-CDI group. Univariate analyses
      demonstrated that old age, receiving antibiotics (OR = 8.70) and glucocorticoids
      (OR = 7.71) 1 month prior to hospitalization, respiratory failure (OR = 3.28) and
      receiving antimicrobials during hospitalization (OR = 1.15) were the risk factors
      associated with CDI. Multivariate conditional logistic regression analysis
      demonstrated the similar results. CONCLUSION: CDI was common among patients
      discharged from hospital for HAP at a university hospital. Prevention of the
      spreading of C. difficile among hospitalized patients is urgently needed.

PMID- 28497296
TI  - Preferential flow characteristics of reclaimed mine soils in a surface coal mine
      dump.
AB  - There are a large number of macropores/tubular channels of a few centimeters and
      plant roots in reclaimed dump soils, which are the main reasons for the formation
      of soil macropores and soil preferential flow. To systematically study the
      morphological characteristics and variation of soil preferential flow for
      different reclaimed vegetations in a dump, a dye-staining experiment and physical
      and chemical analysis were carried out to investigate the formation mechanism and
      influencing factors of soil preferential flow in the vegetation restoration
      process. The results indicate that there were differences in the soil water
      breakthrough curves for different plots. The macropore effluent rate generally
      increased at first and then tended to stabilize. The soil steady effluent rate
      decreased with increasing soil depth, which reached the maximum and minimum
      values at the depths of 0~5 cm (0.0193~0.0315 mm s-1) and 50~60 cm (0.0028~0.0035
      mm s-1), respectively. Furthermore, the radius of soil macropores under different
      types of reclaimed vegetation ranged from 0.03 to 4.71 mm, most of which ranged
      from 0.11 to 2.36 mm. The soil macroporosity of different reclaimed vegetation
      types ranged from 0.03 to 16.58%, which was significantly greater than 5%. The
      soil macroporosity determined 65% of the variation in the steady effluent rate
      and 42% of the variation in the saturated hydraulic conductivity. Furthermore,
      the dye coverage ratio decreased as the soil layer depth increased in different
      plots, and there were some differences in each plot. The maximum dye coverage
      ratio occurred in the 0~5 cm soil layer, which reached 90.37%. The dye coverage
      ratio at a depth of 0~60 cm in six plots followed the order of Robinia
      pseudoacacia (26.48%) > Ulmus pumila (20.12%) > mixed forest (17.32%) > farmland
      (15.06%) > shrub (13.97%) > weeds (10.07%). The soil preferential flow mostly
      occurred in the 0~40 cm soil depth layer, which occupied more than 93% of the
      total soil profile (0~60 cm). Moreover, a Pearson correlation was used to analyze
      the relationship between environmental factors (soil, water, and plant factors)
      and the dye coverage ratio. The dye coverage ratio of soil preferential flow
      under different reclamation vegetations was very significantly or significantly
      positively correlated with the gravel content, mean radius of soil macropores,
      soil saturated hydraulic conductivity, root weight density, and root length
      density, which promoted the formation and development of soil preferential flow.
      This study will provide a scientific basis for understanding the formation
      mechanism and perfecting the research system of soil preferential flow,
      vegetation restoration, and reconstruction in a dump; furthermore, this research
      offers significance guidance in the construction of green mines and the
      development of regional economics.

PMID- 28497298
TI  - Erratum to: Changing Places, Changing Plates? A Binational Comparison of Barriers
      and Facilitators to Healthful Eating Among Central American Communities.

PMID- 28497297
TI  - Assessing the influence of different plant species in drainage ditches on
      mitigation of non-point source pollutants (N, P, and sediments) in the Purple
      Sichuan Basin.
AB  - Three different types of ditches, each 300 m in length, were employed in this
      study. One vegetated constructed ditch (VCD), three natural vegetated soil
      ditches (NVSD), and three constructed ditches left unvegetated (UCD) as controls
      were investigated using simple in/out mass balances and uptake by plant species
      with a potential for phytoremediation and their mechanisms. Significant
      differences in the ditches were observed, suggesting the importance of plant
      species in nutrient mitigation. The removal rates of TN (total nitrogen) and TP
      (total phosphorus) were 64.28 and 58.02, 31.16 and 27.49, and 3.91 and 2.97%,
      respectively, in the VCD, NVSD, and UCD. Canna indica (45.12 g m-2) and Oenanthe
      javanica (21.48 g m-2) had the highest total N and P storage in the VCD and NVSD.
      Furthermore, species C. indica possessed the highest annual N and P uptake in the
      VCD (216.59 kg N/ha/yr and 30.73 kg P/ha/yr). In the NVSD, species O. javanica
      had the greatest annual N and P uptake (96.66 kg N/ha/yr and 7.94 kg P/ha/yr).
      Both VCD and NVSD were found to have a reasonably good outcome compared to UCD.
      Retention of nutrients by ditch sediments was probably the major attenuation
      mechanism, with subsequent plant uptake and microbial nitrification
      denitrification of the nutrients as secondary removal mechanisms. Results of this
      study highlight the importance of taking actions for establishment of appropriate
      plant species inside the ditches in order to enhance its direct and indirect
      roles and maximize purification rate in aquatic environments.

PMID- 28497299
TI  - Ecotoxicological and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons
      (PAHs) in Short-Neck Clam (Paphia undulata) and Contaminated Sediments in Malacca
      Strait, Malaysia.
AB  - The distribution, sources, and human health risk assessment of polycyclic
      aromatic hydrocarbons (PAHs) in surface sediment and the edible tissue of short
      neck clam (Paphia undulata) from mudflat ecosystem in the west coast of Malaysia
      were investigated. The concentrations of ?16 PAHs varied from 347.05 to 6207.5
      and 179.32 to 1657.5 ng g-1 in sediment and short-neck clam samples,
      respectively. The calculations of mean PEL quotients (mean-PELQs) showed that the
      ecological risk of PAHs in the sediment samples was low to moderate-high level,
      whereas the total health risk through ingestion and dermal contact was
      considerably high. The PAHs biota sediment accumulation factors data for short
      neck clam were obtained in this study, indicating a preferential accumulation of
      lower molecular weight PAHs. The source apportionment of PAHs in sediment using
      positive matrix factorization model indicated that the highest contribution to
      the PAHs was from diesel emissions (30.38%) followed by oil and oil derivate and
      incomplete coal combustion (23.06%), vehicular emissions (16.43%), wood
      combustion (15.93%), and natural gas combustion (14.2%). A preliminary evaluation
      of human health risk using chronic daily intake, hazard index, benzo[a]pyrene
      equivalent (BaPeq) concentration, and the incremental lifetime cancer risk
      indicated that PAHs in short-neck clam would induce potential carcinogenic
      effects in the consumers.

PMID- 28497300
TI  - [(Partial) fusion of the wrist : Indications and surgical procedures].
AB  - Carpal bone fusions for secondary reconstruction are still indispensable despite
      state of the art diagnostic tools and modern treatment techniques for wrist
      lesions. The former fusions stabilize the wrist and enable sufficient residual
      carpal mobility. Pain can be reduced significantly by arthrodesis of destroyed
      joints and the progress of osteoarthritis may be stopped or delayed. This review
      presents commonly used fusions with their inherent indications, contraindications
      and complications.

PMID- 28497302
TI  - Keys for the morphological identification of the Australian paralysis ticks
      (Acari: Ixodidae), with scanning electron micrographs.
AB  - The Australian paralysis ticks (Ixodes: Sternalixodes) are of considerable
      medical and veterinary importance within Australia. This is because of their
      ability to cause paralysis but also their capacity to transmit pathogens and
      induce allergic reactions. The available keys for the identification of the group
      (Ixodes holocyclus Neumann, Ixodes cornuatus Roberts, and Ixodes hirsti Hassall)
      are ambiguous and contain errors, making accurate identification of the group
      difficult. Illustrations of varying quality and accuracy of these species have
      been published in the past; however, they have never been collectively treated
      using scanning electron microscopy (SEM). Female Australian paralysis ticks are
      here examined using SEM, and the first pictorial key for this group is presented
      along with an accurate text key.

PMID- 28497301
TI  - Various Regulatory Modes for Circadian Rhythmicity and Sexual Dimorphism in the
      Non-Neuronal Cardiac Cholinergic System.
AB  - Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS)
      regulated by a positive feedback system; however, its other regulatory mechanisms
      remain to be elucidated, which include the epigenetic control or regulation by
      the female sex steroid, estrogen. Here, the NNCCS was shown to possess a
      circadian rhythm; its activity was upregulated in the light-off phase via histone
      acetyltransferase (HAT) activity and downregulated in the light-on phase.
      Disrupting the circadian rhythm altered the physiological choline
      acetyltransferase (ChAT) expression pattern. The NNCCS circadian rhythm may be
      regulated by miR-345, independently of HAT, causing decreased cardiac ChAT
      expression. Murine cardiac ChAT expression and ACh contents were increased more
      in female hearts than in male hearts. This upregulation was downregulated by
      treatment with the estrogen receptor antagonist tamoxifen, and in contrast,
      estrogen reciprocally regulated cardiac miR-345 expression. These results suggest
      that the NNCCS is regulated by the circadian rhythm and is affected by sexual
      dimorphism.

PMID- 28497303
TI  - Review of cattle ticks (Acari, Ixodida) in Ivory Coast and geographic
      distribution of Rhipicephalus (Boophilus) microplus, an emerging tick in West
      Africa.
AB  - The exotic tick Rhipicephalus (Boophilus) microplus was discovered in Ivory Coast
      in 2007 and then gradually in other countries in West Africa. It is known to
      induce significant losses in farming and to replace other species of the same
      genus. In order to contribute to improve health and productivity of cattle in
      Ivory Coast regarding the emergence of this dreaded tick, a study was conducted
      to determine the current geographic distribution of the tick R. (B.) microplus
      and review cattle ticks in general. To this end, 23,460 ticks were collected from
      180 farms located throughout the country. Ten species of ticks belonging to the
      genus Rhipicephalus (including those of the subgenus Boophilus), Hyalomma and
      Ambyomma were identified. It was found that the exotic tick R. (B.) microplus has
      invaded the entire Ivorian territory and is now the main cattle tick (63.6% of
      ticks collected), followed by Amblyomma variegatum that remains still dominant in
      the North. The population of indigenous species of Rhipicephalus (Boophilus) is
      in drastic decline.

PMID- 28497304
TI  - Acaricidal activity of Havardia albicans and Caesalpinia gaumeri methanolic leaf
      extracts on Rhipicephalus microplus and its toxicity to laboratory animals.
AB  - The acaricidal activity of methanolic extracts from the leaves of Havardia
      albicans (Kunth Britton and Rose) and Caesalpinia gaumeri (Greenm) were tested on
      the larvae and adults of the cattle tick Rhipicephalus microplus Canestrini using
      the larval immersion test and the adult immersion test, respectively. The
      toxicity of these extracts was also evaluated on laboratory animals using
      toxicity bioassays at different concentrations: skin irritability (500 mg/ml),
      acute oral toxicity (5000 mg/kg), ocular irritability (1000 mg/ml) and dermal
      toxicity (5000 mg/kg). The acaricidal activity of the H. albicans extracts on R.
      microplus larvae showed a LC50 of 7.0% (4.3-11.4) and a LC99 of 25.5% (14.26
      201.5). The acaricidal activity of the C. gaumeri extracts on larvae showed a
      LC50 of 7.8% (5.74-10.65) and a LC99 of 38.32% (22.22-146.48). The H. albicans
      extracts showed moderate acaricidal activity in the inhibition of egg laying
      (54.4 +/- 12.4) and the inhibition of larval hatching (48.7 +/- 6.8) in R.
      microplus adults. The C. gaumeri extracts also showed moderate acaricidal
      activity in the inhibition of egg laying (51.0 +/- 11.2). However, none of the
      evaluated extracts showed significant toxicity on laboratory rodents. These
      plants show the potential to control R. microplus and could be administered
      topically or orally in animals. Further studies are needed to identify the active
      compound(s) and to evaluate the effects of these plants on R. microplus in vivo.

PMID- 28497308
TI  - Transient abducens nerve palsy after cervical traction.

PMID- 28497305
TI  - Deep Brain Stimulation Emergencies: How the New Technologies Could Modify the
      Current Scenario.
AB  - After 25 years of deep brain stimulation (DBS) for the treatment of Parkinson's
      disease, it has become increasingly recognized that a range of postoperative
      urgent situations and emergencies may occur. In this review we describe the
      possible scenarios of DBS-related emergencies: perioperative (intraoperative and
      early postoperative) and postoperative settings and issues from suboptimal
      control of motor and nonmotor symptoms in the early programming phase and during
      long-term follow-up. We also outline potential advantages in the management of
      these emergencies offered by the newest devices, emerging technologies, and new
      possibilities in programming.

PMID- 28497306
TI  - Triterpenoid saponins from Polaskia chichipe Backbg. and their inhibitory or
      promotional effects on the melanogenesis of B16 melanoma cells.
AB  - Five new oleanane-type saponins 1-5 together with a known saponin 6 and a
      steroidal glycoside 7 were isolated from Polaskia chichipe Backbg., and their
      structures were determined from their 1D and 2D NMR and HRFABMS spectral data.
      The six isolated saponins 1-6 were tested for their effects on the melanogenesis
      of B16 melanoma 4A5 cells. Compound 1 exerted an inhibitory effect at 100 MUM
      whereas compound 3 promoted melanogenesis at the same concentration, even though
      these two compounds contain the same aglycon structure. The dose-dependent
      activities of compounds 1 and 3 on melanin synthesis were investigated.

PMID- 28497309
TI  - The correlation of lymphocyte subsets, natural killer cell, and Parkinson's
      disease: a meta-analysis.
AB  - The correlation between immunity and Parkinson's disease was presented in many
      papers, which also discussed lymphocyte and natural killer cell. But these
      studies have yielded inconsistent results. To systematically review the
      relationship between the lymphocyte subsets/natural killer cell and the risk of
      Parkinson's disease, we electronically searched the SpringerLink, Web of Science,
      Ebsco-medline with full text, Pubmed, Elsevier-ScienceDirect, Ovid-lww-oup,
      Wanfang Data for case-control trials on comparing the number of peripheral blood
      lymphocyte subsets and natural killer cell in Parkinson's patients and healthy
      controls. According to the Cochrane methods, the reviewers selected literature,
      extracted data, and assessed the quality. Then, a meta-analysis was performed
      using RevMan 5.2. Finally, 21 case-control trials including 943 cases of
      Parkinson's disease were fit into our data analysis. Meta-analysis showed that
      the decreased numbers of CD3+, CD4+ lymphocyte subsets and the increased number
      of natural killer cell were found in Parkinson's disease patients. In the
      intermediate and late stage of PD, CD8+ lymphocyte subsets had a significant
      decrement. However, the number of B lymphocyte subsets had no significant
      association with Parkinson's disease. The lymphocyte subsets and NK cell may be
      associated with the risk of Parkinson's disease.

PMID- 28497310
TI  - Use of cell phones and brain tumors: a true association?

PMID- 28497311
TI  - Circulating TNF-alpha levels increased and correlated negatively with IGF-I in
      postoperative cognitive dysfunction.
AB  - Signaling pathways of tumor necrosis factor-alpha (TNF-alpha) and insulin-like
      growth factor-I (IGF-I) are found to be functionally interrelated in some
      experimental studies. IGF-I may be involved in the pathogenesis of postoperative
      cognitive dysfunction (POCD). In order to investigate the possible interaction of
      TNF-alpha and IGF-I in POCD, the plasma levels of IGF-I and TNF-alpha were
      determined in 44 patients under general anesthesia. As compared with non-POCD
      patients, POCD patients showed increased TNF-alpha and decreased IGF-I levels in
      plasma, as well as a significant negative correlation between TNF-alpha and IGF-I
      values. The present results suggest that interaction of increased TNF-alpha
      levels and decreased IGF-1 levels might lead to a vicious circle, which may
      contribute to POCD.

PMID- 28497312
TI  - Phenytoin: neuroprotection or neurotoxicity?
AB  - Phenytoin is an 80-year young molecule and new indications are still emerging.
      The neuroprotective potential of phenytoin has been evaluated for decades.
      Recently, a positive phase II trial supported its further development in the
      treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral
      neuritis was first reported to be an adverse event of phenytoin, and since then a
      small but steady stream of publications discussed peripheral polyneuropathy as
      being a possible adverse event of phenytoin. We have reviewed the literature and
      concluded there is some supportive evidence for a reversible polyneuropathy after
      the oral use of phenytoin, though with no evidence for clear neurotoxicity on the
      level of peripheral nerves. This is probably due to the fact that the
      pharmacological effects of phenytoin, based on the stabilizing effect of the
      voltage-gated sodium channels, make impairment of nerve conduction in
      asymptomatic and symptomatic reversible polyneuropathies plausible. Clear
      toxically-induced phenytoin-related polyneuropathies, however, are extremely rare
      and are always related to high dose or high plasma levels of phenytoin, mostly
      developing during many years of therapy. We could only find one case of a
      probable reversible chronic phenytoin intoxication resulting in a biopsy proven
      axonal atrophy with secondary demyelination and signs of remyelination. All case
      series and case reports published are insufficient in detail to prove a clear
      causal relation between phenytoin intake and the induction of a peripheral
      polyneuropathy. Phenytoin does not lead to irreversible toxicity of the
      peripheral nerves and might, on the other hand, have neuroprotective properties.

PMID- 28497313
TI  - Lewis P. Rowland, MD.

PMID- 28497314
TI  - [Legal aspects of aging].

PMID- 28497315
TI  - Energy-coupling mechanism of the multidrug resistance transporter AcrB: Evidence
      for membrane potential-driving hypothesis through mutagenic analysis.

PMID- 28497316
TI  - Quality assurance trials for Ki67 assessment in pathology.
AB  - Ki67 is a broadly used proliferation marker in surgical pathology with an obvious
      need for standardization to improve reproducibility of assessment. Here, we
      present results of the so far only existing round robin tests on Ki67, organized
      annually in Germany, Austria, and Switzerland from 2010 to 2015 with up to 160
      participating laboratories (QuIP). In each quality assessment trial, eight probes
      from each breast cancer, neuroendocrine tumor, and malignant lymphoma were
      compiled on a tissue microarray (TMA). TMAs were stained in the participants'
      laboratories with antibodies and procedures also applied in their daily routine.
      Participating pathologists were expected to assign Ki67 values to one of four
      different categories for each tumor type. All local stainings and evaluations
      were reassessed by the organizing panel and compared to a preset standard. On
      average, 95% of participants reached the benchmark of over 80% concordance rates
      with the Ki67 category pre-established by the panel. Automatization and type of
      antibody did not affect the success rate. Concordance rates differed between
      tumor entities being highest in each tumor type with either very high or very low
      labeling indices. Lower rates were seen for intermediate Ki67 levels. Staining
      quality improved during the observation period as did inter-observer concordance
      with 85% of participants achieving excellent agreement (kappa > 0.8) in the first
      year and over 95% in 2015. In conclusion, regular external quality assurance
      trials have been established as a tool to improve the reproducibility and
      reliability of the prognostic and predictive proliferation marker Ki67.

PMID- 28497317
TI  - Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma.
AB  - Radiation therapy has historically been the pillar of curative treatment for
      Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever
      increasing recognition of treatment-related morbidity in long-term survivors, the
      role of radiotherapy has evolved significantly. Modern combined modality therapy
      (CMT) with multi-agent chemotherapy followed by involved site radiation therapy
      (ISRT) to initially involved sites of disease remains the gold standard for the
      majority of patients with HL. Reduction of long-term treatment-related toxicity
      has become the major driver in clinical trial design for early-stage HL while
      improved disease-specific survival remains the goal in patients with more
      advanced and unfavorable disease. This review will address the data supporting
      the use of radiotherapy in HL as well as specific methods for reducing late
      toxicity from radiotherapy.

PMID- 28497318
TI  - Controlled Ion Release from Novel Polyester/Ceramic Composites Enhances
      Osteoinductivity.
AB  - Due to the growing number of patients suffering from musculoskeletal defects and
      the limited supply of and sub-optimal outcomes associated with biological graft
      materials, novel biomaterials must be created that can function as graft
      substitutes. For bone regeneration, composite materials that mimic the organic
      and inorganic phases of natural bone can provide cues which expedite and enhance
      endogenous repair. Specifically, recent research has shown that calcium and
      phosphate ions are inherently osteoinductive, so controllably delivering their
      release holds significant promise for this field. In this study, unique aliphatic
      polyesters were synthesized and complexed with a rapidly decomposing ceramic
      (monobasic calcium phosphate, MCP) yielding novel polymer/ceramic composite
      biomaterials. It was discovered that the fast dissolution and rapid burst release
      of ions from MCP could be modulated depending on polymer length and chemistry.
      Also, controlled ion release was found to moderate solution pH associated with
      polyester degradation. When composite biomaterials were incubated with
      mesenchymal stems cells (MSCs) they were found to better facilitate osteogenic
      differentiation than the individual components as evidenced by increased alkaline
      phosphate expression and more rapid mineralization. These results indicate that
      controlling calcium and phosphate ion release via a polyester matrix is a
      promising approach for bone regenerative engineering.

PMID- 28497319
TI  - Trends in and relation between hip fracture incidence and osteoporosis medication
      utilization and prices in Estonia in 2004-2015.
AB  - : Osteoporosis medicines reduce osteoporotic fractures. There is a very strong
      negative correlation between the consumption of medicines and the price of an
      average daily dose indicating that affordability is a key factor that could
      increase consumption of antiosteoporotic medicines and, through that, reduce
      fractures. PURPOSE: Osteoporosis is a major cause of morbidity and mortality in
      the modern world. Our study aims to describe the trends in incidence of hip
      fractures in relation to drug utilization patterns and the average price of
      antiosteoporotic medicines in Estonia. METHODS: Data on hip fractures was
      obtained from the medical claims database of Estonian Health Insurance Fund
      (EHIF). Consumption and price data was obtained from the Estonian State Agency of
      Medicines (SAM).Consumption is presented using WHO defined daily doses
      methodology, and the prices reflect the average wholesale price of medicines.
      RESULTS: From 2004 to 2010 there was a non-significant increasing trend in
      standardized hip fracture incidence in Estonia, but from 2010 to 2015, the trend
      turned to a significant decrease of 4.5% per year. The consumption of
      osteoporosis medication increased significantly from 2004 to 2009 by yearly
      average of 41.2%. After 2009, the consumption levelled. On contrast, the average
      price of one daily dose of osteoporosis medication decreased significantly from
      2004 to 2009 by 16.9% per year and the decrease also levelled after 2009. This
      gives a very strong negative correlation of -0.93 (p < 0.001) between the
      consumption of antiosteoporotic medication and the average price of a daily dose
      of medication during the study period. CONCLUSIONS: The statistically significant
      decline of standardized incidence of hip fractures from 2010 onward could at
      least in part be the result of the high increase in consumption of
      antiosteoporotic medicines which in turn is strongly negatively correlated with
      the average price of osteoporosis medicines.

PMID- 28497320
TI  - Accelerating drug development by efficiently using emerging PK/PD data from an
      adaptable entry-into-human trial: example of lumretuzumab.
AB  - PURPOSE: This study aimed at evaluating if pharmacokinetic and pharmacodynamic
      data from the first few patients treated with an investigational monoclonal
      antibody in a dose-escalation study can be used to guide the early initiation of
      potentially more efficacious combination regimens. METHODS: Emerging
      pharmacokinetic and pharmacodynamic data from the first nine patients treated
      with lumretuzumab (a glycoengineered anti-HER3 monoclonal antibody) monotherapy
      at doses from 100 to 400 mg q2w were used along with a pharmacokinetic model that
      incorporated target-mediated drug disposition to guide the selection of the
      starting dose for use in combination regimens. RESULTS: The dose-escalation study
      investigated lumretuzumab doses up to 2000 mg q2w and a maximum tolerated dose
      was not reached. However, the model described in this report predicted linear
      lumretuzumab pharmacokinetics and >95% target saturation at doses >=400 mg q2w.
      These data, along with safety data, contributed to the decision to begin dose
      escalation studies in combination with cetuximab and erlotinib using a starting
      dose of 400 mg lumretuzumab. Pharmacokinetic data from patients treated with
      lumretuzumab 400-2000 mg q2w in combination regimens were consistent with the
      model predictions. CONCLUSION: PK/PD modelling of emerging clinical data might
      accelerate development programs by enabling additional parts of a trial to
      commence before completion of the monotherapy part. The dose and schedule of
      lumretuzumab were optimised for concomitant therapy at doses substantially below
      the highest dose investigated.

PMID- 28497322
TI  - Oral and video presentations.

PMID- 28497321
TI  - Predicting Cumulative and Maximum Brain Strain Measures From HybridIII Head
      Kinematics: A Combined Laboratory Study and Post-Hoc Regression Analysis.
AB  - Due to growing concern on brain injury in sport, and the role that helmets could
      play in preventing brain injury caused by impact, biomechanics researchers and
      helmet certification organizations are discussing how helmet assessment methods
      might change to assess helmets based on impact parameters relevant to brain
      injury. To understand the relationship between kinematic measures and brain
      strain, we completed hundreds of impacts using a 50th percentile Hybrid III head
      neck wearing an ice hockey helmet and input three-dimensional impact kinematics
      to a finite element brain model called the Simulated Injury Monitor (SIMon) (n =
      267). Impacts to the helmet front, back and side included impact speeds from 1.2
      to 5.8 ms-1. Linear regression models, compared through multiple regression
      techniques, calculating adjusted R 2 and the F-statistic, determined the most
      efficient set of kinematics capable of predicting SIMon-computed brain strain,
      including the cumulative strain damage measure (specifically CSDM-15) and maximum
      principal strain (MPS). Resultant change in angular velocity, Deltaomega R,
      better predicted CSDM-15 and MPS than the current helmet certification metric,
      peak g, and was the most efficient model for predicting strain, regardless of
      impact location. In nearly all cases, the best two-variable model included peak
      resultant angular acceleration, alpha R, and Deltaomega R.

PMID- 28497323
TI  - Why null results do not mean no results: negative findings have implications for
      policy, practice, and research.

PMID- 28497324
TI  - Erratum to: The Presence of Norovirus and Adenovirus on Environmental Surfaces in
      Relation to the Hygienic Level in Food Service Operations Associated with a
      Suspected Gastroenteritis Outbreak.

PMID- 28497325
TI  - The effect of pressure-controlled inverse ratio ventilation on lung protection in
      obese patients undergoing gynecological laparoscopic surgery.
AB  - SPECIFIC AIM: To examine the effects of pressure-controlled inverse ratio
      ventilation (PCIRV) and volume-control ventilation (VCV) on arterial oxygenation,
      pulmonary function, hemodynamics, levels of surfactant protein A (SP-A), and
      tumor necrosis factor-alpha (TNF-alpha) in obese patients undergoing
      gynecological laparoscopic surgery. METHODS: Sixty patients, body mass index
      (BMI) >=30 kg/m2, scheduled for elective gynecological laparoscopic surgery were
      enrolled in the study. Patients were randomly allocated to receive either PCIRV
      with an inspiratory-expiratory (I:E) ratio of 1.5:1 (PCIRV group n = 30) or VCV
      with an I:E ratio of 1:2 (VCV group n = 30). Ventilation variables, viz. tidal
      volume (V T), dynamic respiratory-system compliance (C RS), driving pressure
      (DeltaP = V T/C RS), arterial blood oxygen partial pressure/fraction of
      inspiration oxygen (PaO2/FiO2) and arterial blood carbon dioxide partial pressure
      (PaCO2), were measured. Hemodynamic variables, viz. mean arterial pressure (MAP),
      heart rate (HR), and serum levels of SP-A and TNF-alpha, were also measured.
      RESULTS: When compared to patients in the VCV group, patients in the PCIRV group
      had higher V T, dynamic CRS, and PaO2/FiO2, and lower DeltaP and PaCO2 at 20 and
      60 min after the start of pneumoperitoneum (p < 0.05). Patients in the PCIRV
      group had lower SP-A and TNF-alpha levels at 24 and 48 h after surgery than those
      in the VCV group (p < 0.05). CONCLUSION: In obese patients undergoing
      gynecological laparoscopic surgery, PCIRV can improve ventilation, promote gas
      exchange and oxygenation, and is associated with decreased levels of SP-A and TNF
      alpha. These effects demonstrate improved lung protection provided by PCIRV in
      this patient population.

PMID- 28497326
TI  - Evaluation of pelvic inflammatory disease potential in cholinesterase inhibitor
      pesticide-exposed females.
AB  - Cholinesterase inhibitor pesticides, mainly organophosphates and carbamates, are
      commonly used in Egypt. Chronic exposure of males and females working in
      agriculture is expected. The study aimed to relate exposure to cholinesterase
      inhibitor pesticides to the development of pelvic inflammatory disease (PID).
      This is a case-control study that was conducted among 84 females. Seventy
      patients complained of pelvic inflammatory disease visited the outpatient
      Gynecology and Obstetrics Clinic. Fourteen females were not suffering from PID
      and were chosen as a control group. Red blood cells' cholinesterase activity was
      measured in blood. Cervical swaps were collected, and cultures were submitted for
      microbiological examination. The results showed that cholinesterase activities
      were significantly depressed in exposed females (6.36 +/- 0.8 MUmoles/min/ml red
      cells) when compared to non-exposed (7.5 +/- 1.2 MUmoles/min/ml red cells), and
      both were significantly depressed when compared with healthy females (9.17 +/-
      0.7 MUmoles/min/ml red cells). The correlation coefficient (r) between previous
      exposure and the laboratory confirmed cervical infection was 0.31, with a P value
      of 0.009. The study concluded that exposure to cholinesterase inhibitor
      pesticides could increase the occurrence of pelvic inflammatory disease.

PMID- 28497328
TI  - Overexploitation of karst spring as a measure against water scarcity.
AB  - Water scarcity, especially in the hydrologically critical part of the year, is a
      problem often present in many cities and regions, particularly in arid and sub
      arid areas. Climate change and human water demand compound the problem. This
      paper discusses a climate change adaptation measure-the possibility of karst
      spring overexploitation, where there is a siphon-shaped cavity inside the
      mountain. The pilot area is near the city of Nis, where a decreasing
      precipitation trend has already been observed and is expected to continue in the
      future. The paper also presents some basic information related to the pilot area
      and undertaken investigations. The project, successfully implemented in 2004, has
      provided the city of Nis with an additional amount of 200 l/s of spring water
      during the most critical part of the year.

PMID- 28497327
TI  - Variation in Cd accumulation among radish cultivars and identification of low-Cd
      cultivars.
AB  - Heavy metals have serious health consequences and ecosystem impacts. A pot
      experiment was conducted to investigate the variation of cadmium (Cd) uptake and
      accumulation among 40 cultivars of radish (Raphanus sativus L.) at three Cd
      levels, including 0.31 (T1), 0.83 (T2), and 1.13 (T3) mg kg-1. Most of the tested
      cultivars had higher taproot biomass in the T3 treatment when compared to those
      in the T1 treatment, indicating a Cd stress-induced growth in radish. Taproot Cd
      concentrations in 95 and 5% of the tested cultivars were lower than 0.1 mg kg-1
      (fresh weight, FW) in the T1 and T2 treatments, respectively; however, there was
      no cultivar suitable for safe consumption in the T3 treatment. Radish production
      showed potential risk of Cd pollution as high as some leafy vegetables when grown
      in the soils where Cd concentration exceeded 0.8 mg kg-1. When compared with
      Chinese heat-resisting or imported cultivars, Chinese common cultivars had
      significantly higher taproot Cd concentrations. Three low-Cd cultivars and five
      high-Cd cultivars were identified. Taproot Cd concentrations showed significant
      correlations between any two of the three treatments (p < 0.01), suggesting that
      Cd accumulation in taproot of radish was genotype-dependent.

PMID- 28497329
TI  - Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas.
AB  - 5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic
      DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels
      have been associated with cadmium (Cd) exposure in humans, but such information
      is lacking for invertebrate bioindicators. Here, we aimed to determine whether
      this epigenetic mark is present in DNA of the hepatopancreas of the land snail
      Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared
      under laboratory conditions and exposed to graded amounts of dietary cadmium for
      14 days. Weight gain was used as a sublethal endpoint, whereas survival as a
      lethal endpoint. Our results are the first to provide evidence for the presence
      of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the
      measured values falling below 0.03%. This is also the first study to investigate
      the interplay of Cd with DNA hydroxymethylation levels in a non-human animal
      study system. Cadmium retention in the hepatopancreas of C. aspersus increased
      from a dietary Cd dose of 1 milligram per kilogram dry weight (mg/kg d. wt). For
      the same treatment, we identified the only significant elevation in percentage of
      samples with detectable 5hmC levels despite the lack of significant mortalities
      and changes in weight gain among treatment groups. These findings indicate that
      5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening
      a new aspect to invertebrate environmental epigenetics.

PMID- 28497330
TI  - Development of nanoemulsion from Vitex negundo L. essential oil and their
      efficacy of antioxidant, antimicrobial and larvicidal activities (Aedes aegypti
      L.).
AB  - It is believed that nanoemulsions were emerged as a promising candidate to
      improve the qualities of natural essential oil towards antimicrobial and
      insecticidal applications. In the present study, we have focused on the
      encapsulation of Vitex negundo L. leaf essential oil using Polysorbate80 for its
      different biological activities including antioxidant, bactericidal and
      larvicidal activity against dengue fever vector Aedes aegypti L. Initially, the
      nanoemulsion was prepared by low energy method and droplet size of the formulated
      nanoemulsion was characterized by using Dynamic Light Scattering analysis. The
      freshly prepared V. negundo essential nanoemulsion was observed with the mean
      droplet size of below 200 nm indicating its excellent stability. Further, the
      larvicidal activity of essential oil and nanoemulsion with various concentrations
      (25, 50, 100, 200 and 400 ppm). The larvicidal activities were tested 2nd and 3rd
      instar larval mortality rate that was observed against the 12 and 24 h exposure
      period. After a 12 h exposure period, the larvicidal activities of 2nd instar
      larva were observed as essential oil (73.33 +/- 1.88), nanoemulsion (81.00 +/-
      0.88) and the larvicidal activities of 3rd instar larva were displayed essential
      oil (70.33 +/- 2.60) and nanoemulsion (79.00 +/- 3.70). Likewise, after a 24 h
      exposure period, the larvicidal activities of 2nd instar larva were observed as
      essential oil (90.30 +/- 2.15), nanoemulsion (94.33 +/- 1.20) and the larvicidal
      activities of 3rd instar larva were essential oil (80.66 +/- 0.66) and
      nanoemulsion (93.00 +/- 1.25) respectively. We finally concluded that the
      developed plant-based emulsion essential oil systems were thermodynamically
      stable. Owing to its improved bioavailability and biocompatibility, formulated
      nanoemulsion can be used in various biomedical applications including drug
      delivery as well as disease transmitting mosquito vector control. Graphical
      abstract ?.

PMID- 28497331
TI  - Zingiber cernuum (Zingiberaceae) essential oil as effective larvicide and
      oviposition deterrent on six mosquito vectors, with little non-target toxicity on
      four aquatic mosquito predators.
AB  - Mosquitoes are responsible for the transmission of many pathogens and parasites,
      which cause serious diseases in humans and animals. Currently, botanical products
      have been suggested as alternative tools in the fight against arthropod vectors.
      In this study, the essential oil (EO) extracted from Zingiber cernuum was tested
      as larvicide and oviposition deterrent on six mosquito species of public health
      relevance, including malaria and Zika virus vectors. The EO showed high toxicity
      on third instar larvae of Anopheles stephensi (LC50 = 41.34 MUg/ml), Aedes
      aegypti (LC50 = 44.88 MUg/ml), Culex quinquefasciatus (LC50 = 48.44 MUg/ml),
      Anopheles subpictus (LC50 = 51.42 MUg/ml), Aedes albopictus (LC50 = 55.84
      MUg/ml), and Culex tritaeniorhynchus (LC50 = 60.20 MUg/ml). In addition, low
      doses of Z. cernuum EO reduced oviposition rates in six mosquito species. The
      acute toxicity of Z. cernuum EO on four mosquito predators was scarce; LC50
      ranged from 3119 to 11,233 MUg/ml. Overall, our results revealed that the Z.
      cernuum EO can be considered for the development of effective and environmental
      friendly mosquito larvicides and oviposition deterrents.

PMID- 28497332
TI  - Toxicity of nickel to soil microbial community with and without the presence of
      its mineral collectors-a calorimetric approach.
AB  - The toxicity of nickel and three of its main collectors, sodium isopropyl
      xanthate (SIPX), sodium ethyl xanthate (SEX), and potassium ethyl xanthate (PEX)
      to soil microbial activity, was analyzed, individually and as a binary
      combination of nickel and each of the collectors. The investigation was performed
      through the microcalorimetric analysis method. For the single chemicals, all
      power-time curves exhibited lag, exponential, stationary, and death phases of
      microbial growth. Different parameters exhibited a significant adverse effect of
      the analyzed chemicals on soil microbial activity, with a positive relationship
      between the inhibitory ratio and the chemical dose (p < 0.05 or p < 0.01). A peak
      power reduction level of 24.23% was noted for 50 MUg g-1 soil in the case of Ni
      while for the mineral collectors, only 5 MUg g-1 soil and 50 MUg g-1 soil induced
      a peak power reduction level of over 35 and 50%, respectively, in general. The
      inhibitory ratio ranged in the following order: PEX > SEX > SIPX > Ni. Similar
      behavior was observed with the mixture toxicity whose inhibitory ratio
      substantially decreased (maximum decrease of 38.35%) and slightly increased
      (maximum increase of 15.34%), in comparison with the single toxicity of mineral
      collectors and nickel, respectively. The inhibitory ratio of the mixture toxicity
      was positively correlated (p < 0.05 or p < 0.01) with the total dose of the
      mixture. In general, the lesser and higher toxic effects are those of mixtures
      containing SIPX and PEX, respectively.

PMID- 28497334
TI  - Short Overview.
AB  - Mitochondrial autophagy (mitophagy) is a mitochondrial quality control mechanism
      that selectively removes damaged mitochondria via autophagic degradation.
      Autophagic adaptor/receptor proteins contribute to the selective degradation of
      damaged mitochondria by autophagy. A part of them containing both ubiquitin
      binding domains and Atg8 interacting motif (AIM)/LC3 interacting region (LIR)
      motifs, which bind to the autophagy-related protein 8 (Atg8) family (LC3 and
      GABARAP family), lead ubiquitylated (damaged) mitochondria to selective removal.
      On the other hand, some specific outer mitochondrial membrane-anchored proteins
      containing AIM/LIR motif function as another type of autophagy adaptor/receptor
      proteins. Here I briefly summarize mechanisms of mitophagy and its related
      proteins.

PMID- 28497333
TI  - Next-Generation Sequencing-based genomic profiling of brain metastases of primary
      ovarian cancer identifies high number of BRCA-mutations.
AB  - Ovarian cancer represents the most common gynaecological malignancy and has the
      highest mortality of all female reproductive cancers. It has a rare predilection
      to develop brain metastases (BM). In this study, we evaluated the mutational
      profile of ovarian cancer metastases through Next-Generation Sequencing (NGS)
      with the aim of identifying potential clinically actionable genetic alterations
      with options for small molecule targeted therapy. Library preparation was
      conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer
      specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using
      TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA
      gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of
      variant alterations, each with unique molecular profiles. The 37 identified
      variants were distributed over 22 cancer-related genes (23.4%). The number of
      mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most
      commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples
      revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM
      samples showed mutations in at least one DNA repair gene. Our NGS study of BM of
      ovarian carcinoma revealed a significant number of BRCA-mutations beside TP53,
      ATM and CHEK2 mutations. These findings strongly suggest the implication of BRCA
      and DNA repair malfunction in ovarian cancer metastasizing to the brain. Based on
      these findings, pharmacological PARP inhibition could be one potential targeted
      therapeutic for brain metastatic ovarian cancer patients.

PMID- 28497335
TI  - Methods for Analyzing Sphingosine-1-Phosphate Signaling in Human and Mouse
      Primary Mast Cells.
AB  - Mast cells produce a potently bioactive sphingolipid metabolite sphingosine-1
      phosphate (S1P) constitutively and upon activation. The ligation of S1P to its
      type 2 receptor on mast cells triggers a novel downstream signaling pathway that
      we discovered links activation of transcription factor signal transducer and
      activator of transcription 3 to mast cell-derived chemokine release in both
      humans and mice. In this chapter, we describe the methods used to study S1P
      signaling in human and mouse primary mast cells.

PMID- 28497336
TI  - The overlapping spectrum of flat irregular pigment epithelial detachment
      investigated by optical coherence tomography angiography.
AB  - PURPOSE: To describe the OCT angiography characteristics of flat irregular
      pigment epithelial detachments (PEDs), an overlapping tomographic feature of
      various macular disorders. METHODS: Consecutive patients with a dimpled retinal
      pigment epithelium profile on OCT, referred for a second opinion, were enrolled.
      Fluorescein (FA) and indocyanine green angiography (ICGA) were performed in all
      patients and compared to previous examinations, when available. In all patients,
      enhanced depth imaging-OCT and OCT angiography were performed upon referral and
      at subsequent follow-ups. RESULTS: Twenty-five eyes from 25 patients (9 women and
      16 men, mean age of 63.4 years) were enrolled. The diagnoses of CSCR were already
      established by the referring physicians in 10 patients, acute in 15% and chronic
      in 26%; 48% of patients were referred with a diagnosis of type 1 CNV, and 11% of
      CSCR complicated by CNV. After performing OCT angiography, 2 masked examiner
      identified 7 type 1 CNV (29%), 18 eyes with pachychoroid disease of which 31%
      pachychoroid pigment epitheliopathies (PPEs) at baseline evolved to CSCR, 22% PPE
      at baseline evolved to pachychoroid neovasculopathy, 18% pachychoroid
      neovasculopathy stable. CONCLUSION: Central serous chorioretinopathy, type 1 CNV,
      and the pachychoroid spectrum of diseases cause abnormalities in the choroidal
      circulation that make the overlying RPE dysfunctional, resulting in flat
      irregular PED. Discrimination between avascular and vascular flat irregular PEDs
      is crucial for a good visual outcome, but since chronic alterations of the RPE
      can compromise the diagnostic specificity of FA and ICGA, OCT angiography may
      become a fundamental tool to differentiate these clinical entities.

PMID- 28497337
TI  - Identification of calmodulin binding proteins in the entomopathogenic fungus
      Beauveria bassiana.
AB  - Calmodulin (CaM) is a primary Ca2+ receptor and plays a pivotal role in a variety
      of cellular responses in eukaryotes. Even though a large number of CaM-binding
      proteins are well known in yeast, plants, and animals, little is known regarding
      CaM-targeted proteins in filamentous fungi. To identify CaM-binding proteins in
      filamentous fungi, we used a proteomics method coupled with co
      immunoprecipitation (CoIP) and MALDI-TOF/TOF mass spectrometry (MS) in Beauveria
      bassiana. Through this method, we identified ten CaM-binding proteins in B.
      bassiana. One of the CaM-targeted proteins was the heat shock protein 70
      (BbHSP70) in B. bassiana. Our biochemical study showed that ATP inhibits the
      molecular interaction between BbHSP70 and CaM, suggesting a regulatory mechanism
      between CaM and ATP for regulating BbHSP70.

PMID- 28497338
TI  - Decreased Spontaneous Baroreflex Sensitivity as an Early Marker for Progression
      of Haemorrhage.
AB  - INTRODUCTION: Blood donation provides an ideal setup for assessment of
      cardiovascular responses to mild hypovolemia for understanding the underlying
      mechanisms. AIM: To evaluate cardiovascular responses in time and magnitude by
      estimating the spontaneous baroreflex sensitivity (BRS) during and after donation
      of 450 ml of blood. METHODS: Continuous beat-to-beat blood pressure and lead II
      ECG was recorded before, during and after blood donation in 54 healthy volunteers
      (age 34.7 +/- 5.08 years; weight 77.9 +/- 8.20 kg), followed by offline analyses
      of baroreflex sensitivity. RESULTS: The systolic, diastolic or mean blood
      pressures did not change during or after the blood donation. Decrease in pulse
      pressure and increase in heart rate was observed post donation. The spontaneous
      BRS decreased during [8.68 (6.038-12.69) ms/mmHg] and after blood donation [9.401
      (6.396-11.59) ms/mmHg] as compared to the baseline [12.83 (6.884-18.18) ms/mmHg]
      with a significant decrease in alpha-HF on spectral analysis. CONCLUSION: Mild
      blood loss (450 ml) results in non-hypotensive haemorrhage with a decrease in
      spontaneous BRS before the rise of heart rate during blood donation.

PMID- 28497339
TI  - Follow-up of Antihypertensive Therapy Improves Blood Pressure Control: Results of
      HYT (HYperTension survey) Follow-up.
AB  - INTRODUCTION: Although improved during the past few years, blood pressure control
      remains sub optimal. AIM: The impact of follow-up assessment on blood pressure
      control was evaluated in a group of patients of the HYT (HYperTension survey),
      treated with a combination of different dihydropyridine calcium-channel blockers
      (CCBs regimen) and inhibitors of renin-angiotensin-aldosterone system (RAAS) and
      with uncontrolled blood pressure. This was obtained assessing (a) the rate of
      blood pressure control at 3 and 6 months of follow-up in the whole group of
      patients, (b) the rate of blood pressure control and the average blood pressure
      values in subjects treated with different DHP-CCBs regimen. METHODS: From the
      4993 patients with uncontrolled blood pressure, (BP >= 140/90 or >=140/85 in
      patients with diabetes), 3729 (mean age 61.2 +/- 11.5 years), maintained CCBs
      regimen combined wih RAAS blockers and were evaluated at 3 and 6 months follow
      up. At each visit BP (semiautomatic device, Omron-M6, 3 measurements), heart
      rate, adverse events and treatment persistence were collected. RESULTS: At 1st
      and 2nd follow-up the rate of controlled BP was 63.5 and 72.8% respectively (p <
      0.05 vs 35.3% at baseline), whereas in diabetes was 32.5 and 37.9% respectively
      (p < 0.05 vs 20% at baseline). No differences in heart rate were observed. No
      differences in control rate were observed between the different CCBs regimen. The
      incidence of drugs related adverse events was 3.6%. CONCLUSIONS: These findings
      provide evidence that: (a) the follow-up of hypertensive patients under therapy
      increase the rate of blood pressure control; (b) there is no significant
      difference in the antihypertensive effect between different CCBs regimen;

PMID- 28497340
TI  - Glycogen Shunt Activity and Glycolytic Supercompensation in Astrocytes May Be
      Distinctly Mediated via the Muscle Form of Glycogen Phosphorylase.
AB  - Glycogen is the main storage form of glucose in the brain. In contrast with
      previous beliefs, brain glycogen has recently been shown to play important roles
      in several brain functions. A fraction of metabolized glucose molecules are being
      shunted through glycogen before reentering the glycolytic pathway, a phenomenon
      known as the glycogen shunt. The significance of glycogen in astrocyte energetics
      is underlined by high activity of the glycogen shunt and the finding that
      inhibition of glycogen degradation, under some conditions leads to a
      disproportional increase in glycolytic activity, so-called glycolytic
      supercompensation. Glycogen phosphorylase, the key enzyme in glycogen
      degradation, is expressed in two different isoforms in brain, the muscle and the
      brain isoform. Recent studies have illustrated how these are differently
      regulated. In the present study, we investigate the role of the two isoforms in
      glycolytic supercompensation in cultured astrocytes with the expression of either
      one of the isoforms silenced by siRNA knockdown. When reintroducing glucose to
      glucose-starved astrocytes, glycolytic activity increased dramatically.
      Interestingly, the increase was 30% higher in astrocytes not expressing the
      muscle isoform of glycogen phosphorylase. Based on these results and previously
      published data we couple the muscle isoform of glycogen phosphorylase to
      glycolytic supercompensation and glycogen shunt activity, giving insights to the
      underlying mechanistic of these phenomena.

PMID- 28497341
TI  - Chronic TNFalpha Exposure Induces Robust Proliferation of Olfactory Ensheathing
      Cells, but not Schwann Cells.
AB  - TNFalpha is persistently elevated in many injury and disease conditions. Previous
      reports of cytotoxicity of TNFalpha for oligodendrocytes and their progenitors
      suggest that the poor endogenous remyelination in patients with traumatic injury
      or multiple sclerosis may be due in part to persistent inflammation.
      Understanding the effects of inflammatory cytokines on potential cell therapy
      candidates is therefore important for evaluating the feasibility of their use. In
      this study, we assessed the effects of long term exposure to TNFalpha on
      viability, proliferation, migration and TNFalpha receptor expression of cultured
      rat olfactory ensheathing cells (OECs) and Schwann cells (SCs). Although OECs and
      SCs transplanted into the CNS produce similar myelinating phenotypes, and might
      be expected to have similar therapeutic uses, we report that they have very
      different sensitivities to TNFalpha. OECs exhibited positive proliferative
      responses to TNFalpha over a much broader range of concentrations than SCs. Low
      TNFalpha concentrations increased proliferation and migration of both OECs and
      SCs, but SC number declined in the presence of 100 ng/ml or higher concentrations
      of TNFalpha. In contrast, OECs exhibited enhanced proliferation even at high
      TNFalpha concentrations (up to 1 ug/ml) and showed no evidence of TNF
      cytotoxicity even at 4 weeks post-treatment. Furthermore, while both OECs and SCs
      expressed TNFalphaR1 and TNFalphaR2, TNFalpha receptor levels were downregulated
      in OECs after exposure to100 ng/ml TNFalpha for 5-7 days, but were either
      elevated or unchanged in SCs. These results imply that OECs may be a more
      suitable cell therapy candidate if transplanted into areas with persistent
      inflammation.

PMID- 28497342
TI  - Exploration of the Acetylcholinesterase Inhibitory Activity of Some Alkaloids
      from Amaryllidaceae Family by Molecular Docking In Silico.
AB  - Alzheimer's disease (AD) is a progressive condition, where dementia symptoms
      gradually worsen. Biochemically the disease is characterized by the presence of
      neuritic plaques, neurofibrillary tangles, in addition to cholinergic dysfunction
      in the central nervous system. The role of the cholinergic neurotransmission in
      AD is the basis of the widely accepted cholinergic hypothesis. Some of the most
      relevant therapies for the treatment of the disease are based on the
      acetylcholinesterase (AChE) inhibitor activity; however, these therapies are not
      effective to stop the disease progression, but only can temporarily slow down the
      worsening of dementia symptoms, and improve quality of life of patients and their
      caregivers. In recent years, plant alkaloids extracted from Amaryllidaceae family
      have received great attention due to the well-known anti cholinergic activity. In
      this context, the purpose of this study was to apply the docking molecular in
      silico analysis aiming to examine the recombinant human AChE enzyme (rhAChE)
      inhibitory activity displayed by different alkaloids from Amaryllidaceae family.
      Overall, the present results support the idea that alkaloids reported in this
      research are capable of interacting with rhAChE-binding sites.

PMID- 28497343
TI  - BDNF Contributes to Spinal Long-Term Potentiation and Mechanical Hypersensitivity
      Via Fyn-Mediated Phosphorylation of NMDA Receptor GluN2B Subunit at Tyrosine 1472
      in Rats Following Spinal Nerve Ligation.
AB  - Previously we have demonstrated that brain-derived neurotrophic factor (BDNF)
      contributes to spinal long-term potentiation (LTP) and pain hypersensitivity
      through activation of GluN2B-containing N-methyl-D-aspartate (GluN2B-NMDA)
      receptors in rats following spinal nerve ligation (SNL). However, the molecular
      mechanisms by which BDNF impacts upon GluN2B-NMDA receptors and spinal LTP still
      remain unclear. In this study, we first documented that Fyn kinase-mediated
      phosphorylation of GluN2B subunit at tyrosine 1472 (pGluN2BY1472) was involved in
      BDNF-induced spinal LTP and pain hypersensitivity in intact rats. Second, we
      revealed a co-localization of Fyn and GluN2B-NMDA receptor in cultured dorsal
      horn neurons, implying that Fyn is a possible intermediate kinase linking
      BDNF/TrkB signaling with GluN2B-NMDA receptors in the spinal dorsal horn.
      Furthermore, we discovered that both SNL surgery and intrathecal active Fyn could
      induce an increased expression of dorsal horn pGluN2BY1472, as well as pain
      hypersensitivity in response to von Frey filaments stimuli; and more importantly,
      all these actions were effectively abrogated by pre-treatment with either PP2 or
      ifenprodil to respectively inhibit Fyn kinase and GluN2B-NMDA receptors activity.
      Moreover, we found that intrathecal administration of BDNF scavenger TrkB-Fc
      prior to SNL surgery, could prevent the nerve injury-induced increase of both
      pFynY420 and pGluN2BY1472 expression, and also inhibit the mechanical allodynia
      in neuropathic rats. Collectively, these results suggest that Fyn kinase-mediated
      pGluN2BY1472 is critical for BDNF-induced spinal LTP and pain hypersensitivity in
      SNL rats. Therefore, the BDNF-Fyn-GluN2B signaling cascade in the spinal dorsal
      horn may constitute a key mechanism underlying central sensitization and
      neuropathic pain development after peripheral nerve injury.

PMID- 28497344
TI  - Genipin Inhibits LPS-Induced Inflammatory Response in BV2 Microglial Cells.
AB  - Genipin, an aglycon of geniposide, has been reported to have anti-inflammatory
      effect. However, the anti-inflammatory activity of genipin on LPS-stimulated BV2
      microglial cells has not been reported. In this study, we investigated the
      molecular mechanisms responsible for the anti-inflammatory activity of genipin
      both in vivo and in vitro. The levels of TNF-alpha, IL-1beta, NO and PGE2 were
      detected by ELISA. The expression of Nrf2, HO-1, and NF-kappaB were detected by
      western blot analysis. In vivo, genipin significantly attenuated LPS-induced
      memory deficit in the Morris water maze and passive avoidance tasks. Genipin also
      inhibited LPS-induced TNF-alpha and IL-1beta expression in brain tissues. In
      vitro, our results showed that genipin inhibited LPS-induced TNF-alpha, IL-1beta,
      NO and PGE2 production in a concentration-dependent manner. Genipin also
      suppressed LPS-induced NF-kappaB activation. In addition, the expression of Nrf2
      and HO-1 were up-regulated by treatment of genipin. Furthermore, the inhibition
      of genipin on inflammatory mediator production was attenuated by transfection
      with Nrf2 siRNA. In conclusion, genipin inhibited LPS-induced inflammatory
      response by activating Nrf2 signaling pathway in BV2 microglia.

PMID- 28497345
TI  - Retinol (Vitamin A) Increases alpha-Synuclein, beta-Amyloid Peptide, Tau
      Phosphorylation and RAGE Content in Human SH-SY5Y Neuronal Cell Line.
AB  - Retinoids (vitamin A and derivatives) are recognized as essential factors for
      central nervous system (CNS) development. Retinol (vitamin A) also was postulated
      to be a major antioxidant component of diet as it modulates reactive species (RS)
      production and oxidative stress in biological systems. Oxidative stress plays a
      major role either in pathogenesis or development of neurodegenerative diseases,
      or even in both. Here we investigate the role of retinol supplementation to human
      neuron-derived SH-SY5Y cells over RS production and biochemical markers
      associated to neurodegenerative diseases expressed at neuronal level in
      Parkinson's disease and Alzheimer's disease: alpha-synuclein, beta-amyloid
      peptide, tau phosphorylation and RAGE. Retinol treatment (24 h) impaired cell
      viability and increased intracellular RS production at the highest concentrations
      (7 up to 20 uM). Antioxidant co-treatment (Trolox 100 uM) rescued cell viability
      and inhibited RS production. Furthermore, retinol (10 uM) increased the levels of
      alpha-synuclein, tau phosphorylation at Ser396, beta-amyloid peptide and RAGE. Co
      treatment with antioxidant Trolox inhibited the increased in RAGE, but not the
      effect of retinol on alpha-synuclein, tau phosphorylation and beta-amyloid
      peptide accumulation. These data indicate that increased availability of retinol
      to neurons at levels above the cellular physiological concentrations may induce
      deleterious effects through diverse mechanisms, which include oxidative stress
      but also include RS-independent modulation of proteins associated to progression
      of neuronal cell death during the course of neurodegenerative diseases.

PMID- 28497347
TI  - Nano Copper Induces Apoptosis in PK-15 Cells via a Mitochondria-Mediated Pathway.
AB  - Nano-sized copper particles are widely used in various chemical, physical, and
      biological fields. However, earlier studies have shown that nano copper particles
      (40-100 MUg/mL) can induce cell toxicity and apoptosis. Therefore, this study was
      conducted to investigate the role of nano copper in mitochondrion-mediated
      apoptosis in PK-15 cells. The cells were treated with different doses of nano
      copper (20, 40, 60, and 80 MUg/mL) to determine the effects of apoptosis using
      acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow
      cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase
      (SOD) in the PK-15 cells were examined using commercially available kits.
      Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were
      assessed by real-time PCR. The results revealed that nano copper exposure induced
      apoptosis and changed the mitochondrial membrane potential. In addition, nano
      copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS
      genes at a concentration of 40 MUg/mL. To summarize, nano copper significantly (P
      < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells.
      Altogether, these results suggest that nano copper can play an important role in
      inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by
      which nano copper induces nephrotoxicity.

PMID- 28497346
TI  - Enhanced Autophagy Contributes to Protective Effects of GM1 Ganglioside Against
      Abeta1-42-Induced Neurotoxicity and Cognitive Deficits.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The
      aggregation of Abeta peptides, Abeta1-42 in particular, is thought to be a
      fundamental pathogenic mechanism leading to the neuronal damage in AD. Recently,
      monosialoganglioside GM1 is reported to possess pivotal neuroprotection in
      neurodegenerative diseases. Previous studies have focused on the conformational
      dynamics and the biochemical interaction of the amyloid-peptide with the GM1
      ganglioside, as well as the protective effect of GM1 on cognition. However, the
      phenomenon of autophagy with regard to neuronal dysfunction in AD is less
      investigated. In the present study, GM1 treatment were investigated in an AD
      mouse model and cultured PC12 dells to examine cognition-protective and
      neuroprotective effects of GM1. Furthermore, GM1 was found to induce autophagy
      via testing light chain 3 (LC3), Beclin1, neighbor of BRCA1 gene 1 protein and
      p62 (a substrate of LC3). Chloroquine, an inhibitor of lysosomal, was used to
      exclude the interference of lysosome, which could fuse with autophagosome and
      then clear it. In the presence of the inhibitor of autophagy (3-methyladenine; 3
      MA), the protective effect of GM1 on PC12 cells in Abeta (1-42) induced toxic
      conditions was diminished. Interestingly, the expression of histone deacetylase 1
      was increased in PC12 cells when treated with GM1, indicating that autophagy
      might be activated by GM1 through a pathway integrates protein acetylation. This
      study provides a novel insight into the protective role of GM1 against Abeta (1
      42)-induced neurotoxicity via enhancing autophagy.

PMID- 28497348
TI  - Evaluation of Dietary Palygorskite Supplementation on Growth Performance, Mineral
      Accumulations, Antioxidant Capacities, and Meat Quality of Broilers Fed Lead
      Contaminated Diet.
AB  - The objective of this study was to evaluate influence of dietary palygorskite
      (Pal) supplementation on growth performance, mineral accumulations in the tissues
      (livers, kidneys, and muscles), antioxidant capacities, and meat quality of
      broilers fed lead (Pb)-contaminated diet. One-hundred forty-four male broiler
      chicks were randomly divided into three treatment groups, receiving a corn
      soybean meal basal diet (the control group), the basal diet contaminated with 10
      mg/kg Pb (the Pb group), and the basal diet with 10-g/kg Pal supplementation and
      10-mg/kg Pb contamination (the Pal/Pb group) from 1 to 42 days of age,
      respectively. Treatments did not affect growth performance of broilers in the 42
      day study (P > 0.05). Compared with the control group, Pb contamination increased
      Pb accumulation in the livers, kidneys, and muscles (P < 0.05); elevated
      malondialdehyde accumulation in the livers, kidneys, and breast muscles;
      glutathione peroxidase activity in the livers and superoxide dismutase activity
      in the kidneys (P < 0.05); exacerbated drip loss in the pectoralis muscles (P <
      0.05); and reduced glutathione peroxidase activity in the pectoralis muscles (P <
      0.05) of broilers at 42 days of age. The values of these parameters were reversed
      in the Pal/Pb group to levels comparable with those in the control group (P <
      0.05). Additionally, Pal supplementation reduced redness value in the pectoralis
      muscles (P < 0.05), and decreased Cu concentration in the pectoralis muscles and
      livers at 42 days of age as well as its accumulation in the kidneys at both 21
      and 42 days of age compared with the other two groups (P < 0.05). The results
      suggested that dietary Pal supplementation would decrease Pb residue in the
      tissues, alleviate oxidative stress, and affect meat quality of broilers exposed
      to Pb.

PMID- 28497349
TI  - SUV navigator enables rapid [18F]-FDG PET/CT image interpretation compared with
      2D ROI and 3D VOI evaluations.
AB  - PURPOSE: Positron emission tomography (PET) and the maximum standardized uptake
      value (SUVmax) is a useful technique for assessing malignant tumors. Measurements
      of SUVmax in multiple lesions per patient frequently require many time-consuming
      procedures. To address this issue, we designed a novel interface named SUV
      Navigator (SUVnavi), and the purpose of this study was to investigate its
      utility. MATERIALS AND METHODS: We measured SUVmax in 661 lesions from 100
      patients with malignant tumors. Diagnoses and SUVmax measurements were made with
      SUVnavi, 2D, and 3D measurements. SUV measurement accuracy in each method were
      also evaluated. RESULTS: The average reduction in time with SUVnavi versus 2D was
      53.8% and 3D was 37.5%; time required with SUVnavi was significantly shorter than
      with 2D and 3D (P < 0.001 and P < 0.001, respectively). The time reduction and
      lesion number had a positive correlation (P < 0.001 and P < 0.001, respectively).
      SUVmax agreed with precise SUVmax in all lesions measured with SUVnavi and 3D but
      in only 466 of 661 lesions (70.5%) measured with 2D. CONCLUSION: SUVnavi may be
      useful for rapid [18F]-fluorodeoxyglucose positron emission tomography/computed
      tomography ([18F]-FDG PET/CT) image interpretation without reducing the accuracy
      of SUVmax measurement.

PMID- 28497351
TI  - Comment on "Epigenetics in the pathogenesis of RA".

PMID- 28497350
TI  - Synovial cellular and molecular markers in rheumatoid arthritis.
AB  - The profound alterations in the structure, cellular composition, and function of
      synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent
      inflammation and cumulative joint destruction that are hallmarks of this disease.
      In RA, the synovium develops characteristics of a tertiary lymphoid organ, with
      extensive infiltration of lymphocytes and myeloid cells. Concurrently, the
      fibroblast-like synoviocytes undergo massive hyperplasia and acquire a tissue
      invasive phenotype. In this review, we summarize key components of these
      processes, focusing on recently-described roles of selected molecular markers of
      these cellular components of RA synovitis.

PMID- 28497352
TI  - Monogenic Periodic Fever Syndromes: Treatment Options for the Pediatric Patient.
AB  - Autoinflammatory diseases are disorders of the innate immune system characterized
      by uncontrolled inflammation. The most commonly encountered autoinflammatory
      diseases are the hereditary periodic fever syndromes, which present with fever
      and other features of the skin, serosal membranes, and musculoskeletal system.
      The main inherited (monogenic) periodic fever syndromes are familial
      Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor
      necrosis factor receptor-associated periodic syndrome (TRAPS), and
      hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD). Recent
      advances in our understanding of the molecular and pathophysiological basis of
      autoinflammatory diseases have provided new treatment strategies. Patients with
      periodic fever syndromes have clearly benefited from anti-interleukin (IL)-1
      treatment. Colchicine is still the mainstay of FMF therapy, but IL-1 blockade is
      also effective if colchicine fails. Early diagnosis and effective treatment can
      prevent irreversible organ damage. The scope of pathogenic mutations and more
      targeted therapy for better management of these rare diseases remains to be
      defined.

PMID- 28497354
TI  - Farmer-suicide in India: debating the role of biotechnology.
AB  - Indian Biotech opponents have attributed the increase of suicides to the
      monopolization of GM seeds, centering on patent control, application of
      terminator technology, marketing strategy, and increased production costs. The
      contentions of the biotech opponents, however, have been criticized for a lack of
      transparency in their modus operandi i.e. the use of methodology in their
      argumentation. The fact is, however, that with the intention of getting the
      attention of those capable of determining the future of GM cotton in India,
      opponents resorted to generating controversies. Therefore, this article will
      review and evaluate the multifaceted contentions of both opponents and defenders.
      Although the association between seed monopolization and farmer-suicide is
      debatable, we will show that there is a link between the economic factors
      associated with Bt. cultivation and farmer suicide. The underlying thesis of
      biotech opponents becomes all the more significant when analysed vis-a-vis the
      contention of the globalization critics that there has been a political and
      economic marginalization of the Indian farmers. Their accusation assumes
      significance in the context of a fragile democracy like India where market forces
      are accorded precedence over farmers' needs until election time.

PMID- 28497355
TI  - The Generation of Dehydroalanine Residues in Protonated Polypeptides: Ion/Ion
      Reactions for Introducing Selective Cleavages.
AB  - We examine a gas-phase approach for converting a subset of amino acid residues in
      polypeptide cations to dehydroalanine (Dha). Subsequent activation of the
      modified polypeptide ions gives rise to specific cleavage N-terminal to the Dha
      residue. This process allows for the incorporation of selective cleavages in the
      structural characterization of polypeptide ions. An ion/ion reaction within the
      mass spectrometer between a multiply protonated polypeptide and the sulfate
      radical anion introduces a radical site into the multiply protonated polypeptide
      reactant. Subsequent collisional activation of the polypeptide radical cation
      gives rise to radical side chain loss from one of several particular amino acid
      side chains (e.g., leucine, asparagine, lysine, glutamine, and glutamic acid) to
      yield a Dha residue. The Dha residues facilitate preferential backbone cleavages
      to produce signature c- and z-ions, demonstrated with cations derived from
      melittin, mechano growth factor (MGF), and ubiquitin. The efficiencies for
      radical side chain loss and for subsequent generation of specific c- and z-ions
      have been examined as functions of precursor ion charge state and activation
      conditions using cations of ubiquitin as a model for a small protein. It is noted
      that these efficiencies are not strongly dependent on ion trap collisional
      activation conditions but are sensitive to precursor ion charge state. Moderate
      to low charge states show the greatest overall yields for the specific Dha
      cleavages, whereas small molecule losses (e.g., water/ammonia) dominate at the
      lowest charge states and proton catalyzed amide bond cleavages that give rise to
      b- and y-ions tend to dominate at high charge states. Graphical Abstract ?.

PMID- 28497356
TI  - N3 and O2 Protonated Conformers of the Cytosine Mononucleotides Coexist in the
      Gas Phase.
AB  - The gas-phase conformations of the protonated forms of the DNA and RNA cytosine
      mononucleotides, [pdCyd+H]+ and [pCyd+H]+, are examined by infrared multiple
      photon dissociation (IRMPD) action spectroscopy over the IR fingerprint and
      hydrogen-stretching regions complemented by electronic structure calculations.
      The low-energy conformations of [pdCyd+H]+ and [pCyd+H]+ and their relative
      stabilities are computed at the B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and
      MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparisons of the
      measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed
      for the low-energy conformers allow the conformers present in the experiments to
      be determined. Similar to that found in previous IRMPD action spectroscopy
      studies of the protonated forms of the cytosine nucleosides, [dCyd+H]+ and
      [Cyd+H]+, both N3 and O2 protonated cytosine mononucleotides exhibiting an anti
      orientation of cytosine are found to coexist in the experimental population. The
      2'-hydroxyl substituent does not significantly influence the most stable
      conformations of [pCyd+H]+ versus those of [pdCyd+H]+, as the IRMPD spectral
      profiles of [pdCyd+H]+ and [pCyd+H]+ are similar. However, the presence of the 2'
      hydroxyl substituent does influence the relative intensities of the measured
      IRMPD bands. Comparisons to IRMPD spectroscopy studies of the deprotonated forms
      of the cytosine mononucleotides, [pdCyd-H]- and [pCyd-H]-, provide insight into
      the effects of protonation versus deprotonation on the conformational features of
      the nucleobase and sugar moieties. Likewise, comparisons to results of IRMPD
      spectroscopy studies of the protonated cytosine nucleosides provide insight into
      the influence of the phosphate moiety on structure. Comparison with previous ion
      mobility results shows the superiority of IRMPD spectroscopy for distinguishing
      various protonation sites. Graphical Abstract ?.

PMID- 28497357
TI  - Socioeconomic inequalities in treatment of individuals with common mental
      disorders regarding subsequent development of mental illness.
AB  - PURPOSE: Socioeconomic differences appear to be reflected in both, the
      development and the treatment of common mental disorders (CMDs, i.e. depressive,
      anxiety and stress-related disorders). Underlying mechanisms of these
      inequalities are to date not fully understood. This study aimed to investigate if
      (1) there are socioeconomic differences with regard to type of treatment and (2)
      if the socioeconomic status modifies the association between treatment and
      subsequent inpatient care or suicide attempt, respectively, in individuals with
      CMDs. METHODS: The study population comprised 66,097 individuals aged 18-59 on
      sick-leave due to a CMD during 2006 in Sweden. Cox regression with a follow-up
      from 2007 through 2010 estimated crude and multivariate hazard ratios (HR) with
      95% confidence intervals (CI). RESULTS: Individuals with sickness absence due to
      CMDs and a higher educational level were had a lower proportions of specialised
      health care and combined psychiatric medication than their counterparts with
      lower education. However, if high educated CMD patients received more combined
      medication, associations with subsequent mental inpatient care (p < 0.01) and
      suicide attempt (p < 0.05) were stronger than for their counterparts with low
      education. Moreover, previous inpatient care due to mental disorders was
      associated with higher HRs of subsequent suicide attempt in CMD patients with
      high education (HR 5.88; CI 3.02-11.45) compared to those with low education
      (1.96; 1.06-3.60). CONCLUSION: Findings suggest that socioeconomic inequalities
      shape differences in treatment measures and mental health development in
      individuals with CMDs. These differences might signal discrepancies in treatment
      per se or reflect morbidity differences requiring different treatment regimens,
      or may be due to the fact that different diagnoses are given in different
      educational strata due to differential role of stigma.

PMID- 28497358
TI  - Predictive value of selected biomarkers related to metabolism and oxidative
      stress in children with autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) as a neurodevelopmental disorder is characterized
      by impairments in social interaction, communication, and restricted, repetitive
      behavior. Several and reproducible studies have suggested that oxidative stress
      may represent one of the primary etiological mechanism of ASD that can be
      targeted for therapeutic intervention. In the present study, multiple regression
      and combined receiver operating characteristic (ROC) analysis were used to search
      for a relationship between impaired energy and oxidative metabolic pathways in
      the etiology of ASD and to find the linear combination that maximizes the partial
      area under a ROC curve for a pre-identified set of markers related to energy
      metabolism and oxidative stress. Thirty children with ASD and 30 age and gender
      matched controls were enrolled in the study. Using either spectrophotometric or
      ELISA-colorimetric assay, levels of lipid peroxides, vitamin E, vitamin C,
      glutathione (GSH)/glutathione disulfide (GSSG) together with the enzymatic
      activity of catalase, plasma glutathione peroxidase (GPx), and blood superoxide
      dismutase (SOD), were measured in peripheral blood samples, as biomarkers related
      to oxidative stress. Creatine kinase, ectonucleotidases (ADPase and ATPase)
      Na+/K+ (ATPase), lactate, inorganic phosphate, and levels of adenosine
      monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate
      (ATP) together with adenylate energy charge, were also measured as markers of
      impaired energy metabolism. Statistical analysis using ROC curves, multiple and
      logistic regression were performed. A remarkable increase in the area under the
      curve for most of the combined markers, representing both energy impaired
      metabolism or oxidative stress, was observed by using combined ROC analyses.
      Moreover, higher specificity and sensitivity of the combined markers were also
      reported. The present study indicated that the measurement of the predictive
      value of selected biomarkers related to energy metabolism and oxidative stress in
      children with ASD using ROC analysis should lead to the better identification of
      the etiological mechanism of ASD associated with metabolism and diet. Agents with
      activity against the impaired metabolic pathway associated with ASD including the
      metabolic defects and involved enzymes hold a promise as a novel therapy for ASD.

PMID- 28497359
TI  - The pattern of thalamocortical and brain stem projections to the vibrissae
      related sensory and motor cortices in de-whiskered congenital hypothyroid rats.
AB  - The present study is designed to investigate the plastic organization of the
      thalamo-cortical (TC) and brain stem afferents of whisker primary sensory (wS1)
      and motor (wM1) cortical areas in congenital hypothyroid (CH) pups following
      whisker deprivation (WD) from neonatal to adolescence period. Maternal
      hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water
      from early embryonic day 16 to postnatal day (PND) 60. Pregnant rats were divided
      into intact and CH groups (n = 8). In each group, the total whiskers of pups (4
      of 8) were trimmed continuously from PND 1 to PND 60. Retrograde tracing
      technique with WGA-HRP was performed in the present study. Retrogradely labeled
      neurons were observed in the specific thalamic nuclei (VPM and VL) following
      separately WGA-HRP injections into wS1/M1 cortical areas. The number of labeled
      cells in the VPM, VL, VM and PO nuclei of the thalamus significantly decreased in
      CH offsprings rats (P < 0.05). Neonatal WD did not show any significant effects
      on the number of VPM, VL, VM and PO labeled projection neurons to wS1 and wM1
      cortical areas. In addition, retrogradely labeled neurons in dorsal raphe (DR)
      and locus coeruleus (LC) nuclei were observed in all experimental groups. The
      number of DR and LC labeled neurons were higher in the CH and whisker deprived
      groups compared to their matching controls (P < 0.05). Upon our results, CH and
      WD had no synergic or additive effects on the TC and brain stem afferent patterns
      of barrel sensory and motor cortices.

PMID- 28497360
TI  - Neuroprotective effects of Nigella sativa extract upon the hippocampus in PTU
      induced hypothyroidism juvenile rats: A stereological study.
AB  - This study aimed to examine the neuroprotective effects of Nigella sativa (N.
      sativa) in the hippocampus of propylthiouracil (PTU)-induced hypothyroid rats
      during neonatal and juvenile growth. Twenty- five pregnant rats from early
      gestation (GD 0) were divided into five groups: (1) control (received drinking
      water), (2) PTU (received 0.005% PTU in drinking water), (3-5) PTU + NS 0.05%,
      PTU + NS 0.1%, PTU + NS 0.2% (along with PTU, received 0.05%, 0.1% and 0.2% W/V
      of N. sativa respectively) and treatment continued until postnatal day 60 (PN
      60). The brains of male pups were removed for histological and stereological
      assessments. N. sativa extract significantly reduced the production of dark
      neurons and apoptotic cells in different areas of the hippocampus compared to the
      PTU group. Moreover, it significantly attenuated the effect of hypothyroidism on
      the volume reduction of the hippocampus. The results of the present study
      suggested that N. sativa extract has a potential ability to prevent the
      hippocampal neural damage after inducing hypothyroidism during neonatal and
      juvenile growth in rats.

PMID- 28497361
TI  - Design and characterization of lisinopril-loaded superparamagnetic nanoparticles
      as a new contrast agent for in vitro, in vivo MRI imaging, diagnose the tumors
      and drug delivery system.
AB  - Superparamagnetic gamma-Fe2O3@SiO2@lisinopril (MNPs-Lisinopril) nanoparticles are
      T2 and T2* negative contrast agents for magnetic resonance imaging. In this work,
      we report the preparation of lisinopril-coated MNPs for the first time as new T2
      and T2* negative contrast agent for in vitro and in vivo MRI imaging and
      demonstrate the potential it simultaneously for drug delivery system, diagnose
      the tumors and MRI contrast agent. Measurements on the relaxivities (r1, r2 and
      r2*) of the MNPs-Lisinopril were determined in deionized water (in vitro).
      Furthermore, after subcutaneous injection of the MNPs-Lisinopril into 4T1
      (ATCC(r) CRL2539TM) tumor in BALB/c mice, the relaxivities were determined by a
      1.5 T MRI apparatus (in vivo). T2- and T2*-weighted MRI images of MNPs-Lisinopril
      showed that the MR signal intensity decreased significantly with increasing
      nanoparticle concentration in water. With measured r2 values up to 236.66 mM-1s 
      1, our MNPs-Lisinopril show better performance than commercial alternatives. Also
      we tested drug release of Lisinopril coated MNPs at two different pHs. The MNPs-
      Lisinopril is a pH-sensitive drug delivery system and releases different amounts
      of lisinopril from MNPs-Captopril in different pHs.

PMID- 28497362
TI  - Size and shape-dependent cytotoxicity profile of gold nanoparticles for
      biomedical applications.
AB  - Metallic nanoparticles, in particular gold nanoparticles (AuNPs), offer a wide
      spectrum of applications in biomedicine. A crucial issue is their cytotoxicity,
      which depends greatly on various factors, including morphology of nanoparticles.
      Because metallic nanoparticles have an effect on cell membrane integrity, their
      shape and size may affect the viability of cells, due to their different
      geometries as well as physical and chemical interactions with cell membranes.
      Variations in the size and shape of gold nanoparticles may indicate particular
      nanoparticle morphologies that provide strong cytotoxicity effects. Synthesis of
      different sized and shaped bare AuNPs was performed with spherical (~ 10 nm),
      nanoflowers (~ 370 nm), nanorods (~ 41 nm), nanoprisms (~ 160 nm) and nanostars
      (~ 240 nm) morphologies. These nanostructures were characterized and interacting
      with cancer (HeLa) and normal (HEK293T) cell lines and cell viability tests were
      performed by WST-1 tests and fluorescent live/dead cell imaging experiments. It
      was shown that various shapes and sizes of gold nanostructures may affect the
      viability of the cells. Gold nanospheres and nanorods proved to be more toxic
      than star, flower and prism gold nanostructures. This may be attributed to their
      small size and aggregation process. This is the first report concerning a
      comparison of cytotoxic profile in vitro with a wide spectrum of bare AuNPs
      morphology. The findings show their possible use in biomedical applications.

PMID- 28497363
TI  - Spatial Updating Strategy Affects the Reference Frame in Path Integration.
AB  - This study investigated how spatial updating strategies affected the selection of
      reference frames in path integration. Participants walked an outbound path
      consisting of three successive waypoints in a featureless environment and then
      pointed to the first waypoint. We manipulated the alignment of participants'
      final heading at the end of the outbound path with their initial heading to
      examine the adopted reference frame. We assumed that the initial heading defined
      the principal reference direction in an allocentric reference frame. In
      Experiment 1, participants were instructed to use a configural updating strategy
      and to monitor the shape of the outbound path while they walked it. Pointing
      performance was best when the final heading was aligned with the initial heading,
      indicating the use of an allocentric reference frame. In Experiment 2,
      participants were instructed to use a continuous updating strategy and to keep
      track of the location of the first waypoint while walking the outbound path.
      Pointing performance was equivalent regardless of the alignment between the final
      and the initial headings, indicating the use of an egocentric reference frame.
      These results confirmed that people could employ different spatial updating
      strategies in path integration (Wiener, Berthoz, & Wolbers Experimental Brain
      Research 208(1) 61-71, 2011), and suggested that these strategies could affect
      the selection of the reference frame for path integration.

PMID- 28497364
TI  - Concreteness and abstraction in everyday explanation.
AB  - A number of philosophers argue for the value of abstraction in explanation.
      According to these prescriptive theories, an explanation becomes superior when it
      leaves out details that make no difference to the occurrence of the event one is
      trying to explain (the explanandum). Abstract explanations are not frugal
      placeholders for improved, detailed future explanations but are more valuable
      than their concrete counterparts because they highlight the factors that do the
      causal work, the factors in the absence of which the explanandum would not occur.
      We present several experiments that test whether people follow this prescription
      (i.e., whether people prefer explanations with abstract difference makers over
      explanations with concrete details and explanations that omit descriptively
      accurate but causally irrelevant information). Contrary to the prescription, we
      found a preference for concreteness and detail. Participants rated explanations
      with concrete details higher than their abstract counterparts and in many cases
      they did not penalize the presence of causally irrelevant details. Nevertheless,
      causality still constrained participants' preferences: They downgraded concrete
      explanations that did not communicate the critical causal properties.

PMID- 28497365
TI  - Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a
      systematic scoping review.
AB  - The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an
      important diagnostic test and disease marker in hemophagocytic
      syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine
      receptor is rarely measured in clinical practice and has been excluded from
      recent diagnostic/classification criteria such as the HScore and macrophage
      activation syndrome (MAS) 16. We performed a systematic scoping review of 64
      articles (1975-2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty
      two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only
      three distinct datasets actually address sensitivity. The original HLH-2004
      Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r >=
      2400, based on a pediatric dataset (n = 152) which is published for the first
      time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r
      >= 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n =
      27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles
      described sIL-2r as a dynamic marker of disease activity that falls with response
      to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor
      prognostic marker. The ability of sIL-2r to distinguish between subtypes of
      HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as
      a diagnostic and disease marker in HPS/HLH, but also reveals the need for more
      primary data about its performance characteristics, particularly in adults. More
      emphasis should be made in including this simple, inexpensive test in clinical
      practice and studies of HPS/HLH.

PMID- 28497366
TI  - Evaluation of persistence and distribution of intra-dermally administered PKH26
      labelled goat bone marrow derived mesenchymal stem cells in cutaneous wound
      healing model.
AB  - The current study was designed to study the persistence and distribution of
      caprine bone marrow derived mesenchymal stem cells (cBM-MSCs) when administered
      intra-dermally in experimentally induced cutaneous wounds in rabbits. MSC's from
      goat bone marrow were isolated and their differentiation potential towards
      adipogenic and osteogenic lineages were assayed in vitro. The isolated cells were
      phenotypically analysed using flow cytometry for the expression of MSC specific
      matrix receptors (CD73, CD105 and Stro-1) and absence of hematopoietic lineage
      markers. Further, these in vitro expanded MSCs were stained with PKH26 lipophilic
      cell membrane red fluorescent dye and prepared for transplantation into cutaneous
      wounds created on rabbits. Five, 2 cm linear full thickness skin incisions were
      created on either side of dorsal midline of New Zealand white rabbits (n = 4).
      Four wounds in each animal were implanted intra-dermally with PKH26 labelled cBM
      MSCs suspended in 500 ul of Phosphate Buffer Saline (PBS). Fifth wound was
      injected with PBS alone and treated as negative control. The skin samples were
      collected from respective wounds on 3, 7, 10 and 14 days after the wound
      creation, and cryosections of 6 uM were made from it. Fluorescent microscopy of
      these cryosections showed that the PKH26 labelled transplanted cells and their
      daughter cells demonstrated a diffuse pattern of distribution initially and were
      later concentrated towards the wound edges and finally appeared to be engrafted
      with the newly developed skin tissues. The labelled cells were found retained in
      the wound bed throughout the period of 14 days of experimental study with a
      gradual decline in their intensity of red fluorescence probably due to the dye
      dilution as a result of multiple cell division. The retention of transplanted
      MSCs within the wound bed even after the complete wound healing suggests that in
      addition to their paracrine actions as already been reported, they may have
      direct involvement in various stages of intricate wound healing process which
      needs to be explored further.

PMID- 28497367
TI  - ENPP1 121Q functional variant enhances susceptibility to coronary artery disease
      in South Indian patients with type 2 diabetes mellitus.
AB  - Insulin resistance is associated with endothelial dysfunction and ensuing
      cardiovascular diseases in type 2 diabetes mellitus (T2DM) patients. ENPP1 is a
      key modulator of insulin signaling and its polymorphism, K121Q, increases the
      potency to competitively inhibit insulin receptor binding. We investigated the
      association of ENPP1 121Q variant with coronary artery disease (CAD) in patients
      with and without T2DM in South Indian population. Our study was conducted in 913
      subjects: 198 patients with CAD, 284 patients in whom T2DM and CAD co-exists, 160
      patients with T2DM and no CAD history, and 271 healthy volunteers. Genotyping was
      performed using PCR-RFLP and PCR-DNA sequencing. Genotype frequency of ENPP1 121Q
      was higher in disease groups compared to healthy subjects (p < 0.05). T2DM
      patients who carried polymorphic AC/CC genotypes were at 12.8-fold enhanced risk
      to CAD (95% CI 4.97-37.18, p < 0.01). Moreover we observed that 121Q, both in
      heterozygous and homozygous polymorphic states, was a risk factor for CAD without
      diabetes (OR 4.15, p < 0.01). 121Q variant was associated with T2DM patients with
      no CAD history too, but the risk was statistically insignificant after
      multivariate logistic regression analysis (OR 2.32, p > 0.05). We conclude that
      ENPP1 121Q variant is associated with increased risk for CAD in patients with
      T2DM in South Indian population. We also report that 121Q variant of ENPP1 was an
      independent risk factor for CAD irrespective of diabetic milieu. Factors which
      enhance insulin resistance increase the risk for onset and progression of
      coronary atherosclerosis irrespective of a diabetic background.

PMID- 28497368
TI  - Honeydew honey: biological effects on skin cells.
AB  - Honey is a natural product well known by humankind and now reconsidered for its
      use as topical agent for wound and burn treatments. Floral honey is made by
      honeybees from the nectar of blossoms, while honeydew honey is prepared from
      secretions of plants or excretions of plant-sucking insects. Chemical composition
      is different between blossom and honeydew honeys and there is very few
      information about the biological properties of honeydew honey. So, this study was
      specifically designed to explore the potential wound healing effects of the
      honeydew honey. We used in vitro scratch wound healing model consisting of
      fibroblasts and keratinocytes. Data showed that honeydew honeys is able to
      increase wound closure by acting both on fibroblasts and keratinocytes. Based on
      our findings, honeydew honey has the potential to be useful for clinical
      settings.

PMID- 28497369
TI  - Co-enzyme Q10 and acetyl salicylic acid enhance Hsp70 expression in primary
      chicken myocardial cells to protect the cells during heat stress.
AB  - We investigated the effects of co-enzyme Q10 (Q10) and acetyl salicylic acid
      (ASA) on expression of Hsp70 in the protection of primary chicken myocardial
      cells during heat stress. Western blot analysis showed that Q10 and ASA
      accelerated the induction of Hsp70 when chicken myocardial cells were exposed to
      hyperthermia. In the absence of heat stress, however, neither Q10 nor ASA are
      able to upregulate Hsp70 expression. Analysis of enzymes that respond to cellular
      damage and pathological examination revealed that ectopic expression of ASA and
      Q10 alleviate cellular damage during heat stress. Quantification of heat shock
      factors (HSF) indicated that treatment of ASA increased the expression of HSF-1
      and HSF-3 during heat stress. Treatment with Q10 resulted in the elevation of HSF
      1 expression. Expression of HSF-2 and HSF-4 was not affected by ASA or Q10.
      Subcellular distribution analysis of HSF-1 and HSF-3 showed that in response to
      heat stress ASA promoted nuclear translocation of HSF-1 and HSF-3, while Q10
      promoted only HSF-1 nuclear translocation. Chromatin immunoprecipitation (ChIP)
      analysis indicated that HSF-1 occupies the Hsp70 promoter in chicken primary
      myocardial cells during heat stress and under normal conditions, while HSF-3
      occupies the Hsp70 promoter only during heat stress. Real-time PCR analysis
      revealed that ASA induces HSF-1 and HSF-3 binding to Hsp70 HSE, while Q10 only
      induces HSF1 binding to Hsp70 HSE, in agreement with the impact of HSF1 and HSF3
      silencing on Hsp70 expression. These data demonstrate that ASA and Q10 both
      induce the expression of Hsp70 to protect chicken primary myocardial cells during
      heat stress, but through distinct pathways.

PMID- 28497370
TI  - IGF2BP1: a novel binding protein of p38 MAPK.
AB  - Signal transduction pathways control various biological processes in cells
      leading to distinct cellular functions. Protein-protein interactions and post
      translational modifications are the physiological events that occur in signaling
      pathway. p38 MAPK are known to be involved in regulating wide range of cellular
      processes by interacting and activating relevant signaling molecules by means of
      phosphorylation. Deregulation of p38 MAPK is associated with various pathological
      conditions. In order to get an insight into the role played by p38 MAPK in
      cellular signaling, studies were carried out to identify proteins that interact
      with p38 MAPK. Mass spectrometry was used to identify the proteins present in p38
      MAPK complex obtained by co-immunoprecipitation. Based on mass spectrometry data,
      here we report insulin-like growth factor-II binding protein 1 (IGF2BP1) as a
      novel interacting partner of p38 MAPK. IGF2BP1 is a RNA-binding protein
      predominantly known to be involved in tumor progression. To reconfirm the mass
      spectrometry data, in silico analysis was carried out. Based on different models
      predicted in silico, we report the possible interaction domains of p38MAPK and
      IGF2BP1. Considering the involvement of p38MAPK and IGF2BP1 in cancer, our study
      opens up the possibility of p38MAPK regulating IGF2BP1 function, and the
      possibility of targeting this novel interaction for developing cancer-treating
      drugs is discussed.

PMID- 28497371
TI  - Sestrin 2 attenuates neonatal rat cardiomyocyte hypertrophy induced by
      phenylephrine via inhibiting ERK1/2.
AB  - Cardiac hypertrophy is an adaptive response triggered by many physiological and
      pathological conditions and will lead to heart failure eventually. Sestrin 2,
      which is a stress-responsive protein, was reported to protect heart from ischemia
      reperfusion injury. However, the role of Sestrin 2 in cardiac hypertrophy remains
      unknown. In our present study, we aimed to explore the effects of Sestrin 2 on
      cardiomyocyte hypertrophy. We found that knockdown of Sestrin 2 protein
      aggravated cardiomyocyte hypertrophy induced by phenylephrine (PE), featured by
      increased hypertrophic marker ANP and cell surface area. During this process,
      ERK1/2 cascade was further activated, while p38, JNK1/2, and mTOR signaling
      pathways were not affected by downregulation of Sestrin 2. Moreover,
      overexpression of Sestrin 2 protein protected cardiomyocytes from PE-induced
      hypertrophy and ERK1/2 cascade was suppressed correspondingly. Importantly,
      pharmacological inhibition of ERK1/2 eliminated the exacerbated hypertrophic
      phenotype due to Sestrin 2 protein knockdown. In conclusion, we discovered that
      Sestrin 2 protected against cardiomyocyte hypertrophy induced by PE via
      inhibiting ERK1/2 signaling.

PMID- 28497372
TI  - SCARA5 plays a critical role in the progression and metastasis of breast cancer
      by inactivating the ERK1/2, STAT3, and AKT signaling pathways.
AB  - Scavenger receptor class A member 5 (SCARA5) is a candidate anti-oncogene in
      several malignancies. However, whether SCARA5 is a suppressor gene in breast
      cancer and its role in breast cancer cell growth and metastasis remain to be
      determined. Here, we investigated the biological functions of SCARA5 in the
      progression and metastasis of breast cancer and explored the underlying
      mechanisms. A total of 65 breast cancer patients and three cell lines (ZR-75-30,
      MCF-7, and MDA-MB-231) were analyzed in the study. RT-qPCR, western blotting, and
      immunohistochemistry were used to detect mRNA and protein expression, and
      lymphatic vessel density (LVD) and microvessel density (MVD). MTT, colony
      formation, TUNEL assays, invasion assays and Transwell assays, and flow
      cytometric analyses were used to evaluate the effect of SCARA5 on breast cancer
      cells. SCARA5 was significantly downregulated in breast cancer tissues and cells
      and significantly correlated with tumor size, histological grade, lymph node
      metastasis, pTNM stage, VEGF-A, VEGF-C, LVD, and MVD. SCARA5 overexpression
      significantly suppressed cell proliferation, colony formation, invasion, and
      migration, and induced G0/G1 arrest and apoptosis of ZR-75-30 cells. SCARA5
      decreased the phosphorylation of ERK1/2, AKT, and STAT3, and downregulated
      downstream signaling effectors, including MMP-2, 3, and 9, VEGF-A, VEGF-C, Bax,
      Cyclin B1, Cyclin D1, and Cyclin E1, and upregulated E-cadherin, Bcl-2, and
      caspase 3. SCARA5 is associated with multiple signaling pathways and plays a
      critical role in the progression and metastasis of breast cancer. The present
      results provide the first evidence that SCARA5 inhibits lymphangiogenesis by
      downregulating VEGF-C, thereby inhibiting breast cancer lymphatic metastasis.

PMID- 28497373
TI  - Morphological, Histobiochemical and Molecular Characterisation of Low Lignin
      Phloem Fibre (llpf) Mutant of Dark Jute (Corchorus olitorius L.).
AB  - Lignin is a versatile plant metabolite challenging high-end industrial
      applications of several plant products including jute. Application of
      developmental mutant in regulation of lignification in jute may open up door for
      much awaited jute based diversified products. In the present study, a novel dark
      jute (Corchorus olitorius L.) mutant with low lignin (7.23%) in phloem fibre
      being compared to wild-type JRO 204 (13.7%) was identified and characterised.
      Unique morphological features including undulated stem, petiole and leaf vein
      distinguished the mutant in gamma ray irradiated mutant population. Histological
      and biochemical analysis revealed reduced lignification of phloem fibre cells of
      the plant. RT-PCR analysis demonstrated temporal transcriptional regulation of
      CCoAMT1 gene in the mutant. The mutant was found an extremely useful model to
      study phloem fibre developmental biology in the crop besides acting as a donor
      genetic stock for low lignin containing jute fibre in dark jute improvement
      programme.

PMID- 28497374
TI  - The effect of insulin administration on c-peptide in critically ill patients with
      type 2 diabetes.
AB  - BACKGROUND: In critically ill patients with permissive hyperglycemia, it is
      uncertain whether exogenous insulin administration suppresses or enhances c
      peptide secretion (a marker of pancreatic beta-cell response). We aimed to
      explore this effect in patients with type 2 diabetes. METHODS: We prospectively
      enrolled a cohort of 45 critically ill patients with type 2 diabetes managed
      according to a liberal glucose protocol (target blood glucose 10-14 mmol/l). We
      recorded the administration of insulin and oral hypoglycemic agents and measured
      plasma c-peptide as surrogate marker of endogenous insulin secretion on the first
      two consecutive days in ICU. RESULTS: Overall, 20 (44.4%) patients required
      insulin to achieve target blood glucose. Insulin-treated patients had higher
      glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and
      greater blood glucose levels but lower c-peptide levels on admission. Premorbid
      insulin-requiring diabetes was independently associated with lower admission c
      peptide, whereas greater plasma creatinine was independently associated with
      higher levels. Increases in c-peptide were positively correlated with an increase
      in blood glucose both in patients who did (r = 0.54, P = 0.01) and did not (r =
      0.56, P = 0.004) receive insulin. However, insulin administration was
      independently associated with a greater increase in c-peptide (P = 0.04). This
      association was not modified by the use of oral insulin secretagogues.
      CONCLUSIONS: C-peptide, a marker of beta-cell response, responds to and is
      influenced by glycemia and renal function in critically ill patients with type 2
      diabetes. In addition, in our cohort, exogenous insulin administration was
      associated with a greater increase in c-peptide in response to hyperglycemia.
      Trial Registration Australian New Zealand Clinical Trials Registry
      (ACTRN12615000216516).

PMID- 28497375
TI  - Pearls: Clinical Application of Ranawat's Sign.

PMID- 28497376
TI  - Application of electrospun fibers for female reproductive health.
AB  - Here, we present the current challenges in women's reproductive health and the
      current state-of-the-art treatment and prevention options for STI prevention,
      contraception, and treatment of infections. We discuss how the versatile platform
      of electrospun fibers can be applied to each challenge, and postulate at how
      these technologies could be improved. The void of approved electrospun fiber
      based products yields the potential to apply this useful technology to a number
      of medical applications, many of which are relevant to women's reproductive
      health. Given the ability to tune drug delivery characteristics and three
      dimensional geometry, there are many opportunities to pursue new product designs
      and routes of administration for electrospun fibers. For each application, we
      provide an overview of the versatility of electrospun fibers as a novel dosage
      form and summarize their advantages in clinical applications. We also provide a
      perspective on why electrospun fibers are well-suited for a variety of
      applications within women's reproductive health and identify areas that could
      greatly benefit from innovations with electrospun fiber-based approaches.

PMID- 28497377
TI  - [Choosing wisely recommendations in hematology and oncology].
AB  - Many new diagnostic and therapeutic options have been introduced in the field of
      hematology and medical oncology during recent years. Rational treatment
      recommendations are thus of even greater importance. Five presumably underused
      measures are recommended (positive recommendations), primarily pertaining to
      supportive therapy, but also concerning the selective use of molecular
      diagnostics. Recommendations to avoid unnecessary procedures (negative
      recommendations) involve a possible excessive use of anticancer therapy and
      imaging, and insufficiently selective use of growth factors, antiemetics, and
      targeted therapies.

PMID- 28497378
TI  - [How does physical activity influence mortality?]

PMID- 28497379
TI  - [Choosing wisely recommendations in cardiology].
AB  - This article describes controversially discussed Choosing wisely recommendations
      presented by the German Cardiac Society: anticoagulation therapy in patients with
      atrial fibrillation and "only" moderate stroke risk, on the one hand, and goal
      directed low-density lipoprotein (LDL) cholesterol-lowering, on the other.
      Presuming an adequate regime, patients with atrial fibrillation and only moderate
      risk of stroke (CHA2DS2-VASc Score of 1 in men and of 2 in women) also benefit
      from anticoagulation therapy, even in elderly patients. In patients with coronary
      heart disease, the German Cardiac Society recommends reducing LDL-cholesterol
      serum levels with a statin to values lower than 70 mg/dl (1.8 mmol/l) or at least
      reducing the basal level by 50%. With this recommendation, the German Cardiac
      Society unequivocally prioritizes the "goal-oriented statin therapy" above the
      "statin strategy of fixed dose". The reasons for this preference are discussed.

PMID- 28497381
TI  - Deep Benign Fibrous Histiocytoma of the Anterior Mediastinum Mimicking
      Malignancy.
AB  - The following report describes the case of a 43-year-old male smoker that was
      referred to the rapid access lung clinic with haemoptysis, chest pain, and
      axillary lymphadenopathy-a clinical picture that raised concern for a possible
      underlying malignancy. Preliminary investigations revealed elevated D-dimers, low
      volume haemoptysis, and a normal chest X-ray, which lowered the index of
      suspicion. However, computed tomography (CT) pulmonary angiogram identified a
      right hilar mass, several parenchymal cysts, and a large mediastinal mass. In
      addition, a left-sided adrenal lesion was also discovered following CT abdomen
      pelvis, potentially indicating metastatic disease. Fortunately, a positron
      emission tomography scan failed to detect any metabolic activity in either the
      right hilar mass, left adrenal lesion or the anterior mediastinal mass. CT-guided
      biopsy identified the mediastinal mass as a low-grade spindle cell tumour. Due to
      its large size, the mass was surgically resected and confirmed to be a deep
      benign fibrous histiocytoma. The significance of this report is to highlight a
      clinical presentation suggestive of malignancy but actually resulting from a rare
      variant of a benign tumour. The constellation of regional lymphadenopathy,
      respiratory and gastrointestinal symptoms, lung cysts, an adrenal tumour, and a
      mediastinal mass appeared to suggest a progressive disease pattern more commonly
      associated with malignancy.

PMID- 28497382
TI  - Attenuation of Sulfur Dioxide Damage to Wheat Seedlings by Co-exposure to Nitric
      Oxide.
AB  - The protective function of nitric oxide (NO) has been extensively clarified in
      plant responses to abiotic stresses. However, little is known about the
      regulation of NO in plants exposed to sulfur dioxide (SO2). In the present study,
      we found that co-exposure to NO significantly attenuated SO2-induced wheat
      seedling growth inhibition. Data showed that NO efficiently prevented SO2
      triggered oxidative stress, as indicated by decreasing reactive oxygen species
      production, lipid peroxidation, and electrolyte leakage. This might be attributed
      to the regulatory role of NO in antioxidative defense, such as increasing the
      activities of antioxidative enzymes and the contents of non-enzymatic
      antioxidants. The SO2-caused declines in soluble protein and chlorophyll content
      were efficiently recovered by NO application. Photosynthetic parameters, such as
      net photosynthetic rate, maximum photochemical efficiency, and actual
      photochemical efficiency, were protected by NO. In conclusion, this study
      demonstrated that during SO2 exposure, co-application of NO can efficiently
      alleviate plant damage probably by regulating the antioxidative defense, and
      protecting plant photosynthesis-related process.

PMID- 28497383
TI  - Form of Dietary Methylmercury does not Affect Total Mercury Accumulation in the
      Tissues of Zebra Finch.
AB  - Exposure to mercury in humans, other mammals, and birds is primarily dietary,
      with mercury in the methylated form and bound to cysteine in the tissues of prey
      items. Yet dosing studies are generally carried out using methylmercury chloride.
      Here we tested whether the accumulation of total mercury in zebra finch blood,
      egg, muscle, liver, kidney or brain differed depending on whether dietary mercury
      was complexed with chloride or cysteine. We found no effect of form of mercury on
      tissue accumulation. Some previous studies have found lower accumulation of
      mercury in tissues of animals fed complexed mercury. Much remains to be
      understood about what happens to ingested mercury once it enters the intestines,
      but our results suggest that dietary studies using methylmercury chloride in
      birds will produce similar tissue accumulation levels to those using
      methylmercury cysteine.

PMID- 28497384
TI  - Physiological responses to incremental, interval, and continuous counterweighted
      single-leg and double-leg cycling at the same relative intensities.
AB  - PURPOSE: We compared physiological responses to incremental, interval, and
      continuous counterweighted single-leg and double-leg cycling at the same relative
      intensities. The primary hypothesis was that the counterweight method would
      elicit greater normalized power (i.e., power/active leg), greater
      electromyography (EMG) responses, and lower cardiorespiratory demand. METHODS:
      Graded-exercise tests performed by 12 men (age: 21 +/- 2 years; BMI: 24 +/- 3
      kg/m2) initially established that peak oxygen uptake ([Formula: see text]; 76 +/-
      8.4%), expired ventilation ([Formula: see text]; 71 +/- 6.8%), carbon dioxide
      production ([Formula: see text]; 71 +/- 6.8%), heart rate (HRpeak; 91 +/- 5.3%),
      and power output (PPO; 56 +/- 3.6%) were lower during single-leg compared to
      double-leg cycling (main effect of mode; p < 0.05). On separate days,
      participants performed four experimental trials, which involved 30-min bouts of
      either continuous (50% PPO) or interval exercise [4 * (5-min 65% PPO + 2.5 min
      20% PPO)] in a single- or double-leg manner. RESULTS: Double-leg interval and
      continuous cycling were performed at greater absolute power outputs but lower
      normalized power outputs compared to single-leg cycling (p < 0.001). The average
      EMG responses from the vastus lateralis and vastus medialis were similar across
      modes (p > 0.05), but semitendinosus was activated to a greater extent for single
      leg cycling (p = 0.005). Single-leg interval and continuous cycling elicited
      lower mean [Formula: see text], [Formula: see text], [Formula: see text], HR and
      ratings of perceived exertion compared to double-leg cycling (p < 0.05).
      CONCLUSIONS: Counterweighted single-leg cycling elicits lower cardiorespiratory
      and perceptual responses than double-leg cycling at greater normalized power
      outputs.

PMID- 28497385
TI  - Associations of human skeletal muscle fiber type and insulin sensitivity, blood
      lipids, and vascular hemodynamics in a cohort of premenopausal women.
AB  - PURPOSE: Cardiometabolic disease remains a leading cause of morbidity and
      mortality in developed nations. Consequently, identifying and understanding
      factors associated with underlying pathophysiological processes leading to
      chronic cardio metabolic conditions is critical. Metabolic health, arterial
      elasticity, and insulin sensitivity (SI) may impact disease risk, and may be
      determined in part by myofiber type. Therefore, the purpose of this study was to
      test the hypothesis that type I myofiber composition would be associated with
      high SI, greater arterial elasticity, lower blood pressure, and blood lipids;
      whereas, type IIx myofibers would be associated with lower SI, lower arterial
      elasticity, higher blood pressure, blood lipids. METHODS: Muscle biopsies were
      performed on the vastus lateralis in 16 subjects (BMI = 27.62 +/- 4.71 kg/m2, age
      = 32.24 +/- 6.37 years, 43% African American). The distribution of type I, IIa,
      and IIx myofibers was determined via immunohistochemistry performed on frozen
      cross-sections. Pearson correlation analyses were performed to assess
      associations between myofiber composition, SI, arterial elasticity, blood
      pressure, and blood lipid concentrations. RESULTS: The percentage of type I
      myofibers positively correlated with SI and negatively correlated with systolic
      blood pressure SBP, diastolic blood pressure, and mean arterial pressure (MAP);
      whereas, the percentage of type IIx myofibers were negatively correlated with SI
      and large artery elasticity, and positively correlated with LDL cholesterol, SBP,
      and MAP. CONCLUSIONS: These data demonstrate a potential link between myofiber
      composition and cardiometabolic health outcomes in a cohort of premenopausal
      women. Future research is needed to determine the precise mechanisms in which
      myofiber composition impacts the pathophysiology of impaired glucose and lipid
      metabolism, as well as vascular dysfunction.

PMID- 28497386
TI  - Oral contraceptive pill use and the susceptibility to markers of exercise-induced
      muscle damage.
AB  - PURPOSE: Firstly, to establish whether oral contraceptive pill (OCP) users are
      more susceptible to muscle damage compared to non-users, and secondly, to
      establish whether differences can be attributed to differences in patella tendon
      properties. METHODS: Nine female OCP users and 9 female non-users participated in
      the investigation. Combining dynamometry, electromyography and ultrasonography,
      patella tendon properties and vastus lateralis architectural properties were
      measured pre and during the first of 6 sets of 12 maximal voluntary eccentric
      knee extensions. Serum oestrogen levels were measured on the 7th day of the pill
      cycle and the 14th day of menstrual cycle in OCP users and non-users,
      respectively. Maximal voluntary isometric knee extension torque loss, creatine
      kinase and muscle soreness were measured 48 h pre-damage, post-damage, and 48, 96
      and 168 h post-damage. RESULTS: Oestrogen levels were significantly lower in OCP
      users compared to non-users (209 +/- 115 and 433 +/- 147 pg/ml, respectively, p =
      0.004). Proposed determinants of muscle damage, patella tendon stiffness and
      maximal eccentric torque did not differ between OCP users and non-users. The
      change in creatine kinase from pre to peak was significantly higher in OCP users
      compared to non-users (962 +/- 968 and 386 +/- 474 Ul, respectively, p = 0.016).
      There were no other differences in markers of muscle damage. CONCLUSION: Although
      our findings suggest that, when compared to non-users, the OCP may augment the
      creatine kinase response following eccentric exercise, it does not increase the
      susceptibility to any other markers of muscle damage.

PMID- 28497380
TI  - From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying
      Neuropsychiatric Symptoms.
AB  - The L-type calcium channels (LTCCs) Cav1.2 and Cav1.3, encoded by the CACNA1C and
      CACNA1D genes, respectively, are important regulators of calcium influx into
      cells and are critical for normal brain development and plasticity. In humans,
      CACNA1C has emerged as one of the most widely reproduced and prominent candidate
      risk genes for a range of neuropsychiatric disorders, including bipolar disorder
      (BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder,
      and attention deficit hyperactivity disorder. Separately, CACNA1D has been found
      to be associated with BD and autism spectrum disorder, as well as cocaine
      dependence, a comorbid feature associated with psychiatric disorders. Despite
      growing evidence of a significant link between CACNA1C and CACNA1D and
      psychiatric disorders, our understanding of the biological mechanisms by which
      these LTCCs mediate neuropsychiatric-associated endophenotypes, many of which are
      shared across the different disorders, remains rudimentary. Clinical studies with
      LTCC blockers testing their efficacy to alleviate symptoms associated with BD,
      SCZ, and drug dependence have provided mixed results, underscoring the importance
      of further exploring the neurobiological consequences of dysregulated Cav1.2 and
      Cav1.3. Here, we provide a review of clinical studies that have evaluated LTCC
      blockers for BD, SCZ, and drug dependence-associated symptoms, as well as rodent
      studies that have identified Cav1.2- and Cav1.3-specific molecular and cellular
      cascades that underlie mood (anxiety, depression), social behavior, cognition,
      and addiction.

PMID- 28497387
TI  - Changes in light-, moderate-, and vigorous-intensity physical activity and
      changes in depressive symptoms in breast cancer survivors: a prospective
      observational study.
AB  - PURPOSE: Despite the recommendations for cancer survivors to engage in either
      moderate or vigorous physical activity, light-intensity physical activity may
      also have beneficial effects on mental health. The purpose of this study was to
      examine the associations between light, moderate, and vigorous physical activity
      and depressive symptoms in breast cancer survivors over 1 year post-treatment.
      METHODS: Participants (N = 201) were a sample of breast cancer survivors who self
      reported depressive symptoms and wore an accelerometer for seven consecutive days
      to measure physical activity, on five occasions every 3 months post-treatment for
      cancer. RESULTS: Based on the results of hierarchical linear modeling, relative
      to others (i.e., between-person effects) and to oneself (i.e., within-person
      effects), higher levels of light- and moderate-intensity physical activity, but
      not vigorous-intensity physical activity, were associated with lower scores of
      depressive symptoms. CONCLUSIONS: In the first year post-treatment, increases in
      light- and moderate-intensity physical activity, but not vigorous-intensity
      physical activity, were associated with lower scores of depressive symptoms in
      relation to other study participants (i.e., between-person effects) and when
      participants were compared to their own typical levels of physical activity
      (i.e., within-person effects). The findings may have implications for physical
      activity recommendations following treatment for breast cancer as light-intensity
      physical activity may play a role in mitigating depressive symptoms over the
      first year.

PMID- 28497388
TI  - First experience with electronic feedback of the Psychosocial Assessment Tool in
      pediatric cancer care.
AB  - PURPOSE: The Psychosocial Assessment Tool (PAT) is a brief family screener,
      identifying families at universal or elevated risk for psychosocial problems.
      This study aimed to determine the feasibility and usability of the electronic PAT
      (ePAT) in pediatric cancer care. METHODS: Eighty-six parents of newly diagnosed
      children with cancer (0-18 years) agreed to participate and registered at the
      website www.hetklikt.nu (58%). Seventy-five families completed the ePAT at
      approximately 1 month post-diagnosis. Answers were transformed into an electronic
      PROfile (PAT ePROfile) and fed back to the psychosocial team. Team members
      completed a semi-structured evaluation questionnaire. Feasibility was measured as
      the percentage of website registrations, completed ePATs, and PAT ePROfiles
      reviewed or discussed by the team. Usability included perceived match of the PAT
      ePROfile with the team's own risk estimation, perceived added value, and
      perceived actions undertaken as a result of the PAT ePROfile. RESULTS:
      Feasibility was 70% for website registration, 87% for completed ePATs, 85% for
      PAT ePROfile reviewing, and 67% for ePROfile discussion. Team members reported
      that the PAT ePROfile matched with their own risk estimation (M = 7.92, SD =
      1.88) and did not provide additional information (M = 2.18, SD = 2.30). According
      to the team, actions were undertaken for 25% of the families as a result of the
      PAT ePROfile. More actions were undertaken for families with elevated risk scores
      compared to universal risk scores (p = .007). CONCLUSIONS: Implementation of the
      ePAT seems generally feasible, but it is not always clear how this screener adds
      to current clinical practice. Strategies should be developed together with team
      members to improve quick exchange of ePAT results and allocate care according to
      the needs of the families.

PMID- 28497390
TI  - Garlicin post-conditioning suppresses adhesion molecules in a porcine model of
      myocardial ischemia-reperfusion injury.
AB  - OBJECTIVES: To evaluate whether garlicin post-conditioning can attenuate
      myocardial ischemiareperfusion injury in a catheter-based porcine model of acute
      myocardial infarction (AMI) by affecting adhesion molecules integrin beta1/CD29
      and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). METHODS: Twenty
      two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in
      the model and garlicin groups. AMI porcine model was established in the model and
      garlicin groups. The distal parts of the left anterior descending coronary artery
      in the animals of the model and garlicin groups were occluded by dilated balloon
      for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over
      a period of 1 h, beginning just before reperfusion, in the garlicin group. Real
      time polymerase chain reaction, immunohistochemistry and Western blot were
      carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after
      reperfusion. RESULTS: Hematoxylin-eosin staining showed a better myocardial
      structure in the garlicin group after reperfusion. Compared to the model group,
      garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in
      reperfusion area and no-reflflow area (P<0.05 respectively). CONCLUSIONS:
      Garlicin post-conditioning induced cardio-protection against myocardial ischemia
      reperfusion injury in this catheter-based porcine model of AMI. The cardio
      protective effect of garlicin is possibly owing to suppression of production of
      CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.

PMID- 28497389
TI  - Elucidating and engineering thiopeptide biosynthesis.
AB  - Initially discovered in the mid-twentieth century, thiopeptides constitute a
      diverse family of bacterially produced natural products exhibiting a remarkable
      array of biological properties. Only in the last several years have the details
      of thiopeptide biosynthesis been uncovered by a combination of genomic, genetic,
      and biochemical approaches. Thiopeptides are now known to be ribosomally
      synthesized and subsequently densely modified to carry azol(in)es, dehydro amino
      acids, and various other pathway-specific decorations. The defining feature of
      thiopeptides is a central six-membered nitrogenous ring that constrains peptide
      macrocycles of varying sequences and sizes. Recent landmark studies have defined
      the precisely orchestrated posttranslational modification cascade culminating in
      thiopeptide product formation. Because diverse thiopeptides are processed by a
      relatively small number of well-conserved enzymes, it has been suggested that
      artificial diversification of the precursor peptide could allow a vast new
      chemical space to be explored for clinically important activities. The success of
      this strategy depends on the plasticity of thiopeptide processing machinery, an
      open question that warrants further investigation. There is an urgent need
      therefore to leverage established thiopeptide research platforms to investigate
      substrate-enzyme specificity and devise intelligent diversification strategies
      for library generation. Meanwhile, the distinct genomic signatures of conserved
      thiopeptide-associated genes will enable the continued mining of nature for novel
      compounds and processing enzymes.

PMID- 28497391
TI  - Effect of Lang-Chuang-Ding Decoction () on DNA Methylation of CD70 Gene Promoter
      in Peripheral Blood Mononuclear Cells of Female Patients with Systemic Lupus
      Erythematosus.
AB  - OBJECTIVE: To investigate the effect of Lang-chuang-ding Decoction (, LCD) on the
      expression of DNA methylation of CD70 gene promoter in peripheral blood
      mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE).
      METHODS: PBMCs isolated from female patients with SLE or healthy donors were
      cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The
      mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription
      polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter
      region was detected by methylation-specific PCR. RESULTS: After treated with
      medicated serum for 48 h, the mRNA expression levels of CD70 in PBMCs of SLE
      patients were signifificantly higher than those of healthy donors (P<0.05); the
      DNA methylation levels of CD70 promoter region in PBMCs of SLE patients treated
      with medicated serum for 48 h were signifificantly higher than those treated with
      fetal bovine serum (P<0.01). CONCLUSION: LCD could inhibit CD70 gene expression
      in PBMCs of SLE patients by promoting the DNA methylation of CD70 gene promoter.

PMID- 28497392
TI  - Xuebijing Injection () increases early survival rate by alleviating pulmonary
      vasopermeability in rats subjected to severe burns.
AB  - OBJECTIVE: To investigate the effects of Xuebijing Injection (, XBJ) on survival
      rate and pulmonary vasopermeability in a rat model of severe scald injury.
      METHODS: Rats were divided into two experiments: experiment 1 was monitored for
      12 h post-injury for survival analysis after severe burns; in experiment 2, rats
      were killed for determination of pulmonary vascular permeability and pro
      inflflammatory mediators. In both experiments, rats were subject to third-degree
      50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal
      saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells
      (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and
      then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by
      transwell examination for the permeability of PMECs. Meanwhile, pro
      inflflammatory mediators in PMECs culture supernatant were also investigated.
      RESULTS: The average survival time in the scald+XBJ group was 582.1+/-21.2 min,
      which was signifificantly longer than that in the scald + NS group (345.8+/-25.4
      min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-alpha), E
      selectin, interleukin-6 (IL-6), vascular permeability and water content of lung
      tissues were signifificantly increased in animals after severe burns (P<0.01).
      However, administration of XBJ signifificantly decreased these levels in plasma
      and lung tissue. In in vitro cell experiments, XBJ markedly attenuated
      permeability in PMECs monolayer and reduced the levels of TNF-alpha, IL-6 and
      soluble E-selectin after stimulation with scald serum (P<0.01). CONCLUSIONS: XBJ
      increases early survival rate by alleviating pulmonary vasopermeability and
      inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury.
      XBJ may be a potent drug in treatment of severe burns.

PMID- 28497394
TI  - Embolic effects of Bletilla striata microspheres in renal artery and transplanted
      VX2 liver tumor model in rabbits.
AB  - OBJECTIVES: To evaluate the characteristics of Bletilla striata microspheres
      (BSMs) and its effects as an embolic agent in a rabbit model. METHODS: BSMs were
      prepared with an emulsifification-cool condensation-chemical cross-linking
      method. The characteristics of BSMs in vitro were observed. Embolization
      experiments were performed in renal artery of rabbit and in a rabbit liver VX2
      carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and
      the right renal artery was embolized with BSMs (200 MUm in diameter) in the
      experimental group and with polyvinyl alcohol (PVA) of the same size in the
      control group. The pathological findings were examined with hematoxylin-eosin and
      Masson stainings. Liver and renal functions were tested before and after
      embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were
      randomly divided into 3 groups (n=5). Group A were treated with saline, group B
      with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial
      infusion of BSMs (200 MUm in diameter). Tumor growth rate was evaluated by
      magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor
      vascular endothelial cell growth factor (VEGF) were evaluated through
      immunohistochemical staining. RESULTS: The characteristics of BSMs in vitro were
      in full compliance with the requirements for use in interventional procedures. In
      the renal artery embolization experiment, after BSMs intervention, it was more
      diffificult to form collateral circulation than that with PVAs, and the kidney
      manifested atrophy and calcifification. There were no signifificant difference of
      liver and renal functions in rabbits between groups. In the liver VX2 carcinoma
      embolization experiment, compared with group A, the growth rate of VX2 liver
      tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were
      increased in group B (P<0.05). There were no signifificant difference between
      groups B and C (P>0.05). CONCLUSIONS: The characteristics of BSMs in vitro and in
      vivo meet the requirements for its use as an embolic agent in interventional
      approaches.

PMID- 28497393
TI  - Effect of Miscanthus sinensis var. purpurascens Flower Extract on Proliferation
      and Molecular Regulation in Human Dermal Papilla Cells and Stressed C57BL/6 Mice.
AB  - OBJECTIVES: To investigate the hair growth-promoting effect of Miscanthus
      sinensis var. purpurascens (MSP) flower extracton on in vitro and in vivo models.
      METHODS: MSP flower extract was extracted in 99.9% methanol and applied to
      examine the proliferation of human dermal papilla cells (hDPCs) in vitro at the
      dose of 3.92-62.50 MUg/mL and hair growth of C57BL/6 mice in vivo at the dose of
      1000 MUg/mL. The expression of transforming growth factor beta1 (TGF-beta1),
      hepatocyte growth factor (HGF), beta-catenin, substance P was measured by
      relative quantitative realtime polymerase chain reaction. Histopathological and
      immunohistochemical analysis were performed. RESULTS: MSP (7.81 MUg/mL) down
      regulated TGF-beta1 and up-regulated HGF and beta-catenin in hDPCs (P<0.01). MSP
      (1000 MUg/mL)-treated mice showed the earlier transition of hair follicles from
      the telogen to the anagen phase. The number of mast cells was lower in the MSP
      treated mice than in other groups (P<0.05 vs. NCS group). Substance P and TGF
      beta1 were expressed in hair follicles and skin of the MSP group lower than that
      in negative control. Stem cell factor in hair follicles was up-regulated in the
      MSP-treated mice (P<0.01). CONCLUSIONS: The MSP flower extract may have hair
      growth-promotion activities.

PMID- 28497395
TI  - Cardioprotective effects of Qishen Granule () on sarcoplasmic reticulum Ca2+
      handling in heart failure rats.
AB  - OBJECTIVE: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic
      reticulum (SR) Ca2+ handling in heart failure (HF) model of rats and to explore
      the underlying molecular mechanisms. METHODS: HF rat models were induced by left
      anterior descending coronary artery ligation surgery and high-fat diet feeding.
      Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg
      daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of
      QSG were evaluated by echocardiography and blood lipid testing. Intracellular
      Ca2+ concentration and sarco-endoplasmic reticulum ATPase 2a (SERCA2a) activity
      were detected by specifific assay kits. Expressions of the critical regulators in
      SR Ca2+ handling were evaluated by Western blot and real-time quantitative
      polymerase chain reaction. RESULTS: HF model of rats developed ventricular
      remodeling accompanied with calcium overload and defective Ca2+ release-uptake
      cycling in cardiomyocytes. Treatment with QSG improved contractive function,
      attenuated ventricular remodeling and reduced the basal intracellular Ca2+ level.
      QSG prevented defective Ca2+ leak by attenuating hyperphosphorylation of
      ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating
      transcriptional expression of protein phosphatase 1. QSG also restored Ca2+
      uptake by up-regulating expression and activity of SERCA2a and promoting
      phosphorylation of phospholamban. CONCLUSION: QSG restored SR Ca2+ cycling in HF
      rats and served as an ideal alternative drug for treating HF.

PMID- 28497396
TI  - Progressive Muscle Relaxation Combined with Chinese Medicine Five-Element Music
      on Depression for Cancer Patients: A Randomized Controlled Trial.
AB  - OBJECTIVES: To evaluate the effects of progressive muscle relaxation training
      (PMRT) combined with fifive elements music therapy of Chinese medicine (CM) for
      improving anxiety and depression of cancer patients. METHODS: From June 2015 to
      March 2016, 60 cancer patients were included into the study. The patients were
      randomly assigned to a control group and a treatment group by envelope
      randomization, receiving PMRT and PMRT plus CM five elements music therapy,
      respectively, for 8 weeks. Hospital Anxiety and Depression Scale (HADS), Benefit
      Finding Scales (BFS), Functional Assessment of Chronic Illness Therapy-Spiritual
      (FACIT-Sp), and Intervention Expectations Questionnaire (IEQU) were adopted to
      assess the depression of the two groups before and after the treatment. RESULTS:
      Four cases dropped out during the study, and 29 cases in the treatment group and
      27 in the control group were included in the fifinal analysis. Prior to the
      treatments, the baselines of the 4 questionnaires in the two groups showed no
      difference. After the 8-week treatment, the treatment group presented better
      levels of HADS, BFS and FACIT-Sp scores compared with the control group (P<0.05).
      Among the single items of HADS, 4 items involving vexation, feeling fifidgeted,
      pleasure and prospecting the future in the treatment group were improved compared
      with the control group (P<0.05). CONCLUSIONS: As a simple and reliable and
      effective intervention, PMRT combined with fifive elements music therapy
      mitigated anxiety and depression of cancer patients. Cancer patients have been
      found to respond well to psychological intervention in areas regarding
      stabilisation of emotions, disease awareness, and therapeutic compliance. This
      brings about a great difference in improving their quality of life and
      psychological state, offers an effective approach to better self-management in
      cancer treatment.

PMID- 28497397
TI  - Xuebijing Injection () and Resolvin D1 Synergize Regulate Leukocyte Adhesion and
      Improve Survival Rate in Mice with Sepsis-Induced Lung Injury.
AB  - OBJECTIVE: To investigate the effect of combined application of Xuebijing
      Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying
      mechanisms in mice with sepsisinduced lung injury. METHODS: The cecal ligation
      and puncture (CLP) method was used to develop a mouse sepsis model. Specific
      pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each):
      sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the
      CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 MUL/g body weight),
      RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and
      RvD1), respectively. In each group, 12 mice were used to observe 1-week survival
      rate, while the rest were executed at 12 h. Whole blood was collected for flow
      cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were
      harvested for observing pathological changes, and testing the activity of
      myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule
      1 (ICAM-1). RESULTS: Compared with the CLP group, the histopathological damage of
      the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and
      CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved,
      proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression
      in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01).
      CONCLUSIONS: XBJ together with RvD1 could effectively inhibit leukocyte adhesion,
      reduce lung injury, and improve the survival rate of mice with sepsis.

PMID- 28497399
TI  - Money, Social Relationships and the Sense of Self: The Consequences of an
      Improved Financial Situation for Persons Suffering from Serious Mental Illness.
AB  - During a 9-month period, 100 persons with SMI were given approx. 73 USD per month
      above their normal income. Sixteen of the subjects were interviewed. The
      interviews were analysed according to the methods of thematic analysis. The money
      was used for personal pleasure and to re-establish reciprocal relations to
      others. The ways in which different individuals used the money at their disposal
      impacted their sense of self through experiences of mastery, agency, reciprocity,
      recognition and security. The findings underline the importance of including
      social circumstances in our understanding of mental health problems, their
      trajectories and the recovery process.

PMID- 28497400
TI  - Nothing but Mammals? Review of Tim Clutton-Brock's Mammal Societies : (Wiley,
      2016).

PMID- 28497398
TI  - Early markers of myocardial ischemia: from the experimental model to forensic
      pathology cases of sudden cardiac death.
AB  - The goal of this study was to assess whether early markers of myocardial
      ischemia, identified in a previous experimental work, can be applied in forensic
      pathology cases of sudden, ischemic cardiac death. These markers include
      desphosphorylated connexin 43 (Cx43), JunB, TUNEL assay, myoglobin, and troponin
      T. Fourteen cases of sudden cardiac death with gross and/or histological signs of
      myocardial infarction and 14 cases of sudden cardiac death with signs of early
      ischemia at histology and positive immunoreactions for fibronectin and C5b-9 were
      investigated. The control group was represented by 15 hanging (global hypoxia)
      cases. Immunohistochemical reactions were classified into four degrees and
      compared among groups. Cx43 and JunB were significantly more expressed in hanging
      than in ischemia/infarction, but they showed a different distribution in the
      tissue (sub-endocardial in ischemia/infarction, diffuse in hanging) and a
      different intensity of the signal. TUNEL assay was significantly more expressed
      in the group of early ischemia than in myocardial infarction. Myoglobin and
      troponin T did not show any significantly different expression among the three
      groups. Depletion markers have a limited application in forensic cases, and this
      is mostly because positive (depleted) areas are difficult to distinguish from
      artifactually paler areas. Nuclear markers (JunB and TUNEL), on the other hand,
      require a well-trained eye and a high magnification in order to be distinguished.
      Cx43, JunB, and TUNEL assays were confirmed to be early, sensitive markers for
      myocardial ischemia. Nonetheless, they are not specific, as they are expressed in
      global hypoxia as well, but with a different tissular distribution.

PMID- 28497401
TI  - Using a Film Intervention in Early Addiction Treatment: a Qualitative Analysis of
      Process.
AB  - PURPOSE: There is a need for knowledge about how self-help materials can be made
      useful in treatment for Substance Abuse Disorders (SUD), as a supplement to
      ongoing treatment, or as independent tools for change. OBJECTIVE: In this study,
      we explored the use of self-help films in early addiction treatment, taking into
      account both patient and therapist perspectives, as well as dyadic functions. We
      explored how active mechanisms might be related to intervention format and
      implementation context. A secondary aim was to examine the potential mechanisms
      related to the specific content of the intervention: mindfulness and acceptance
      psychoeducation. METHODS: A qualitative exploratory research design, including a
      general inductive analytic approach, constructivist grounded theory, and source
      triangulation features, was used to code and analyze interview material. Emerging
      themes were developed into concepts, and finally an operational model.
      Participants included 12 patients and 22 therapists, in in-/outpatient addiction
      clinics, all in urban areas of Norway. The purpose of the design was empirical
      grounding of developed concepts, to promote different potential user perspectives
      (patients' and therapists') and obtain process data. RESULTS: The core concept
      constructed, "Alliance as experiential process," gives a description of the data
      where patients and therapists accept or reject the film as a result of an
      experience process conceptualized as alliance formation. The alliance process
      model reflects the observation that patients constructed alliances autonomously,
      while therapists built alliances indirectly through their patients' experiences.
      CONCLUSIONS: Use of a self-help film may be a helpful adjunct to face-to-face
      therapy for patients who create a personally meaningful attachment to the film.
      Mindfulness/acceptance may offer one basic framework for such connection to take
      place.

PMID- 28497403
TI  - Locally advanced rectal cancer: predicting non-responders to neoadjuvant
      chemoradiotherapy using apparent diffusion coefficient textures.
AB  - PURPOSE: The purpose of the study is to evaluate whether apparent diffusion
      coefficient (ADC) textures could identify patient with locally advanced rectal
      cancer (LARC) who would not respond to neoadjuvant chemoradiotherapy (NCRT).
      METHOD: Twenty-six patients who underwent MRI including diffusion-weighted
      imaging at a 3.0 T system before NCRT were enrolled. Texture analysis of pre
      therapy ADC mapping was carried out, and a total of 133 ADC textures as well as
      routine mean ADC value of the primary tumor were extracted for each patient.
      Texture parameters and mean ADC were compared between responsive group and non
      responsive group. Logistic regression was used to determine the independent
      predictors for non-responders. Receiver operating characteristic curve (ROC) was
      performed to evaluate the predictive performance of the significant parameters.
      RESULTS: Eighteen of the 133 texture parameters significantly differed between
      responsive and non-responsive groups (p < 0.05). Further, energy variance and
      SdGa47 were identified as independent predictors for non-responders to NCRT; this
      logistic model achieved an area under the curve (AUC) of 0.908. CONCLUSION:
      Texture analysis based on pre-therapy ADC mapping could potentially be helpful to
      identify patients with LARC who would not respond to NCRT.

PMID- 28497402
TI  - Impact of resection versus no resection of the primary tumor on survival in
      patients with colorectal cancer and synchronous unresectable metastases: protocol
      for a randomized multicenter study (CR4).
AB  - PURPOSE: The purpose of this study was to determine whether patients diagnosed
      with colorectal cancer and synchronous unresectable metastases (stage IV) can
      benefit from resection of the primary tumor in terms of an improvement in cancer
      specific survival. METHODS: Stage IV colorectal cancer patients are eligible for
      inclusion in a randomized multicenter study carried out in 22 hospitals
      throughout Spain. Exclusion criteria are rectal tumors below 12 cm from the anal
      verge or locally advanced tumors, multiple bone or central nervous system
      metastases, and history of another primary cancer. The parallel design of the
      trial includes an arm of systemic chemotherapy alone versus an arm of resection
      of the primary tumor plus systemic chemotherapy after surgery. The primary
      endpoint of the study is cancer-specific survival that is assessed with a minimum
      follow-up of 24 months. Secondary endpoints are postoperative morbidity and
      mortality associated with resection of the primary tumor, complications and need
      of surgery in patients treated with systemic chemotherapy only, safety of
      systemic chemotherapy in both treatment strategies, and quality of life.
      CONCLUSIONS: Confirmation of a survival benefit of surgical resection of the
      primary tumor in stage IV colorectal cancer patients not amenable to curative
      therapy is very relevant from a clinical and societal perspective, particularly
      considering the increase in the incidence and prevalence of colorectal cancer in
      developed countries. ClinicalTrials.gov Identifier: NCT02015923.

PMID- 28497405
TI  - Multimodality imaging findings in rhabdomyolysis and a brief review of
      differential diagnoses.
AB  - Rhabdomyolysis has traditionally been a clinical diagnosis with healthcare
      providers utilizing historical context, physical exam, and laboratory data to
      arrive at a diagnosis. However, there are myriad imaging findings that may be
      corroborative and support the presumptive diagnosis. This paper seeks to review
      imaging findings associated with rhabdomyolysis using different modalities
      including radiography, sonography, computed tomography (CT), magnetic resonance
      imaging (MRI), and bone scintigraphy.

PMID- 28497404
TI  - Sexual dysfunction following rectal cancer surgery.
AB  - INTRODUCTION: Sexual and urological problems after surgery for rectal cancer are
      common, multifactorial, inadequately discussed, and untreated. The urogenital
      function is dependent on dual autonomic sympathetic and parasympathetic
      innervation, and four key danger zones exist that are at risk for nerve damage
      during colorectal surgery: one of these sites is in the abdomen and three are in
      the pelvis. The aim of this study is to systematically review the epidemiology of
      sexual dysfunction following rectal cancer surgery, to describe the anatomical
      basis of autonomic nerve-preserving techniques, and to explore the scientific
      evidence available to support the laparoscopic or robotic approach over open
      surgery. METHODS: According to the PRISMA guidelines, a comprehensive literature
      search of studies evaluating sexual function in patients undergoing rectal
      surgery for cancer was performed in Medline, Scopus, Web of Science, Embase, and
      Cochrane Central Register of controlled trials. RESULTS: An increasing number of
      studies assessing the incidence and prevalence of sexual dysfunction following
      multimodality treatment for rectal cancer has been published over the last 30
      years. Significant heterogeneity in the prevalence of sexual dysfunction is
      reported in the literature, with rates between 5 and 90%. CONCLUSIONS: There is
      no evidence to date in favor of any surgical approach (open vs laparoscopic vs
      robotic). Standardized diagnostic tools should be routinely used to prospectively
      assess sexual function in patients undergoing rectal surgery.

PMID- 28497406
TI  - Assessing the gap in female authorship in the journal Emergency Radiology: trends
      over a 20-year period.
AB  - PURPOSE: To examine trends in female authorship in the journal Emergency
      Radiology from January 1994 to December 2014. METHODS: We obtained institutional
      review board approval for our study. We retrospectively reviewed a total of 1617
      articles published in the journal Emergency Radiology over a 20-year period.
      Original articles, case reports, review articles, and pictorial essays were
      included. The first and last position author's gender was categorized as female
      or male. We analyzed trends by comparing the first and last position authors of
      original articles from the first and last year reviewed. We utilized Chi-square
      test for statistical analysis, with a p value <0.05 noted as significant.
      RESULTS: One thousand four hundred twenty articles met our inclusion criteria.
      There were 1420 first position authors and 1295 last position authors. There were
      125 articles that had a sole author-these authors were considered as first
      position authors only. We determined, as best as possible, the gender of 96% of
      the authors. Overall, female authors were 21% of first position authors (290 of
      1368) and 15% of last position authors (183 of 1246). Thirty-two percent of
      articles with female last position authors also had female first position authors
      (58 of 183). There was a statistically significant increase in female last
      position authors, from 12.9% in 1994 to 21.3% in 2014 (p = 0.026), a non
      significant increase in female first position authors, from 17.5% in 1994 to
      20.9% in 2014 (p = 0.514), and a non-significant increase in articles with both a
      first and last female author, from 25% in 1994 to 35% in 2014 (p = 0.593).
      CONCLUSION: Over the last 20 years, there has been a statistically significant
      upward trend in female last position authors publishing in the journal Emergency
      Radiology.

PMID- 28497407
TI  - Tobacco use is not associated with groin hernia repair, a population-based study.
AB  - PURPOSE: The pathogenesis of groin hernia is not fully understood and some
      suggested risk factors are debatable. This population-based study evaluates the
      association between groin hernia repair and tobacco use. METHOD: An observational
      study based on register linkage between the Swedish Hernia Register and the
      Vasterbotten Intervention Program (VIP). All primary groin hernia repairs
      performed from 2001 to 2013 in the county of Vasterbotten, Sweden, were included.
      RESULTS: VIP provided data on the use of tobacco in 102,857 individuals. Neither
      smoking nor the use of snus, increased the risk for requiring a groin hernia
      repair. On the contrary, heavy smoking decreased the risk for men, HR 0.75 (95%
      CI 0.58-0.96), as did having a BMI over 30 kg/m2 HR (men) 0.33 (95% CI 0.27
      0.40). CONCLUSION: Tobacco use is not a risk factor for requiring a groin hernia
      repair, whereas having a low BMI significantly increases the risk.

PMID- 28497408
TI  - Novel Turn-on Fluorescence Probes for Al3+ Based on Conjugated Pyrazole Schiff
      Base.
AB  - One novel turn-on fluorescence probe founded on conjugated pyrazole Schiff base
      for detecting Al3+ was invented. The UV-vis and fluorescence spectrometer were
      employed to explore optical properties of this probe. The results got from those
      experiments indicated that this fluorescence probe manifested excellent
      sensitivity and selectivity for Al3+ compared with other cations examined(Ag+,
      Co2+, Mg2+, Cu2+, Ni2+, Pb2+,and Zn2+). In addition, this probe displayed a more
      rapid response and remained stable between pH 6 and 9 by investigating the
      fluorescence intensity under different response time and various pH values.
      Remarkably, the detection limit for Al3+ could lower to 1.0*10-9M. Therefore, the
      probe could be potentially applied to the environment for the detection of Al3+,
      and the availability in biological range of pH that could be further studied to
      make this probe apply to biological systems in the future.

PMID- 28497409
TI  - A Rapid and Reliable Method for Total Protein Extraction from Succulent Plants
      for Proteomic Analysis.
AB  - Crassulacean acid metabolism plants have some morphological features, such as
      succulent and reduced leaves, thick cuticles, and sunken stomata that help them
      prevent excessive water loss and irradiation. As molecular constituents of these
      morphological adaptations to xeric environments, succulent plants produce a set
      of specific compounds such as complex polysaccharides, pigments, waxes, and
      terpenoids, to name a few, in addition to uncharacterized proteases. Since all
      these compounds interfere with the analysis of proteins by electrophoretic
      techniques, preparation of high quality samples from these sources represents a
      real challenge. The absence of adequate protocols for protein extraction has
      restrained the study of this class of plants at the molecular level. Here, we
      present a rapid and reliable protocol that could be accomplished in 1 h and
      applied to a broad range of plants with reproducible results. We were able to
      obtain well-resolved SDS/PAGE protein patterns in extracts from different members
      of the subfamilies Agavoideae (Agave, Yucca, Manfreda, and Furcraea), Nolinoideae
      (Dasylirion and Beucarnea), and the Cactaceae family. This method is based on the
      differential solubility of contaminants and proteins in the presence of acetone
      and pH-altered solutions. We speculate about the role of saponins and high
      molecular weight carbohydrates to produce electrophoretic-compatible samples. A
      modification of the basic protocol allowed the analysis of samples by
      bidimensional electrophoresis (2DE) for proteomic analysis. Furostanol glycoside
      26-O-beta-glucosidase (an enzyme involved in steroid saponin synthesis) was
      successfully identified by mass spectrometry analysis and de novo sequencing of a
      2DE spot from an Agave attenuata sample.

PMID- 28497410
TI  - Could monopronucleated ICSI zygotes be considered for transfer? Analysis through
      time-lapse monitoring and PGS.
AB  - PURPOSE: The purpose of this study was to investigate the chromosomal
      constitution and the developmental potential of intracytoplasmic sperm injection
      (ICSI) deriving embryos displaying a single pronucleus at the zygote stage.
      METHODS: Eighty-eight embryos from single pronucleus (1PN) two polar bodies (2PB)
      ICSI zygotes from 64 preimplantational genetic screening (PGS) cycles (October
      2012-December 2014), were retrospectively analyzed. Zygotes were cultured in a
      time-lapse incubator. Embryo biopsy was performed on day 3 and genetic analysis
      approached by array comparative genomic hybridization. RESULTS: Chromosomal
      analysis revealed that 17% (15/88) of embryos derived from 1PN 2PB zygotes were
      diagnosed as euploid. After blastomere biopsy at day 3, the blastocyst rate at
      day 5 was 3.4% (3/88). Only 2.3% (2/88) euploid blastocysts were obtained. In two
      couples and after counseling and patient agreement, the transfer of a euploid
      blastocyst from a 1PN 2PB ICSI zygote was performed resulting in the birth of a
      healthy child. CONCLUSIONS: These results open the possibility to consider
      embryos coming from 1PN 2PB ICSI zygotes for transfer when no other embryos from
      2PN 2PB ICSI zygotes are available and if a PGS diagnosis of euploidy is
      obtained. Confirmation of biparental inheritance is strongly recommended.

PMID- 28497411
TI  - Research amongst Irish surgical trainees: what's the trend?
AB  - INTRODUCTION: A high publication rate for surgical trainees is considered a
      prerequisite for progression to Higher Specialist Training (HST). This rate has
      arguably been decreased by the formation of a new 'run-through' training pathway.
      We aim to quantify the number of publications that the 'new' pathway trainees
      have attained compared to the 'old' pathway trainees. We further aim to compare
      the H-index and average citations between General Surgery (GS) and Trauma and
      Orthopaedic (T&O) trainees. METHODS: Publications from old pathway trainee years
      2007-2014 (T&O n = 59, GS n = 64) were compared with new pathway trainees from
      2015 to 2016 (T&O n = 11, GS n = 12). H-index and average citations were also
      compared for trainees commencing HST years 2007-2009. Statistical analysis
      involved D'Agostino normality testing. An unpaired Student's t test +/- Welch's
      correction was utilised for parametric data and a Mann-Whitney U test for non
      parametric data. RESULTS: The average number of publications attained by the old
      pathway T&O trainee was 4.2 +/- 3.1 and was 3.1 +/- 2.4 for the new trainee. Old
      GS trainees had an average of 6.5 +/- 3.3 publications prior to HST with new GS
      trainees having an average of 3.7 +/- 2.8 publications. The average H-index
      attained for GS trainees on completion of the HST pathway was 5.1 +/- 3.2 and 4.6
      +/- 2.4 for T&O trainees. CONCLUSION: There has been a significant decrease in
      publication rates between new and old GS pathways. No significant changes were
      identified between new and old T&O pathways. There was no difference between H
      index and average citations between specialties.

PMID- 28497413
TI  - Physician Perspectives on Readmissions.

PMID- 28497412
TI  - Improved mortality outcomes over time for weekend emergency medical admissions.
AB  - BACKGROUND: Multiple studies have suggested an association between weekend
      hospital admissions and mortality. These have been limited by potential residual
      confounders and a lack of explanation of causation. AIM: We previously attributed
      adverse weekend outcomes to higher acuity; we have re-examined this question for
      all emergency medical admissions to our institution from 2002 to 2014. METHODS:
      We divided admissions by a weekday or weekend (Friday to Sunday) hospital
      arrival. We utilised a multivariate logistic regression model, to determine
      whether the latter was independently predictive of 30-day in-hospital mortality.
      RESULTS: There were 82,368 admissions in 44,628 patients over the 13-year period.
      Of admissions, 37.4% occurred at the weekend. The Acute Illness Severity Score,
      the Charlson Co-morbidity Index and the Chronic Disabling Disease Score were
      similar by a weekday or weekend admission. The multivariable logistic regression
      showed no increase in 30-day in-hospital mortality for weekend admissions, odds
      ratio 1.07 (95% confidence interval 0.98 to 1.16) (p = 0.11). Since the inception
      of the AMAU, the per patient mortality for a weekend admission has declined from
      13.5% in 2002 to 4.4% in 2014. This represents a relative risk reduction of 67.9%
      with a number needed to treat of 10.8. Outcomes improved similarly for weekday
      and weekend admissions. CONCLUSION: No increase in 30-day in-hospital mortality
      for weekend admissions was found in this study. There has been a substantial
      reduction in mortality for both weekday and weekend admissions over time.

PMID- 28497414
TI  - Interprofessional Health Sciences Education: It's Time to Overcome Barriers and
      Excuses.

PMID- 28497415
TI  - Capsule Commentary on Ivlev et al., Use of Patient Decision Aids Increased
      Younger Women's Reluctance to Begin Screening Mammography: A Systematic Review
      and Meta-Analysis.

PMID- 28497416
TI  - Internal Medicine Point-of-Care Ultrasound Curriculum: Consensus Recommendations
      from the Canadian Internal Medicine Ultrasound (CIMUS) Group.
AB  - Bedside point-of-care ultrasound (POCUS) is increasingly used to assess medical
      patients. At present, no consensus exists for what POCUS curriculum is
      appropriate for internal medicine residency training programs. This document
      details the consensus-based recommendations by the Canadian Internal Medicine
      Ultrasound (CIMUS) group, comprising 39 members, representing 14 institutions
      across Canada. Guiding principles for selecting curricular content were
      determined a priori. Consensus was defined as agreement by at least 80% of the
      members on POCUS applications deemed appropriate for teaching and assessment of
      trainees in the core (internal medicine postgraduate years [PGY] 1-3) and
      expanded (general internal medicine PGY 4-5) training programs. We recommend four
      POCUS applications for the core PGY 1-3 curriculum (inferior vena cava, lung B
      lines, pleural effusion, and abdominal free fluid) and three ultrasound-guided
      procedures (central venous catheterization, thoracentesis, and paracentesis). For
      the expanded PGY 4-5 curriculum, we recommend an additional seven applications
      (internal jugular vein, lung consolidation, pneumothorax, knee effusion, gross
      left ventricular systolic function, pericardial effusion, and right ventricular
      strain) and four ultrasound-guided procedures (knee arthrocentesis, arterial line
      insertion, arterial blood gas sampling, and peripheral venous catheterization).
      These recommendations will provide a framework for training programs at a
      national level.

PMID- 28497418
TI  - Assessing time-of-flight signal-to-noise ratio gains within the myocardium and
      subsequent reductions in administered activity in cardiac PET studies.
AB  - BACKGROUND: Time-of-flight (TOF) is known to increase signal-to-noise ratio (SNR)
      and facilitate reductions in administered activity. Established measures of SNR
      gain are derived from areas of uniform uptake, which is not applicable to the
      heterogeneous uptake in cardiac PET images using fluoro-deoxyglucose (FDG). This
      study aimed to develop a technique to quantify SNR gains within the myocardium
      due to TOF. METHODS: Reference TOF SNR gains were measured in 88 FDG oncology
      patients. Phantom data were used to translate reference SNR gains and validate a
      method of quantifying SNR gains within the myocardium from parametric images
      produced from multiple replicate images. This technique was applied to 13 FDG
      cardiac viability patients. RESULTS: Reference TOF SNR gains of +23% +/- 8.5%
      were measured in oncology patients. Measurements of SNR gain from the phantom
      data were in agreement and showed the parametric image technique to be
      sufficiently robust. SNR gains within the myocardium in the viability patients
      were +21% +/- 2.8%. CONCLUSION: A method to quantify SNR gains from TOF within
      the myocardium has been developed and evaluated. SNR gains within the myocardium
      are comparable to those observed by established methods. This allows guidance for
      protocol optimization for TOF systems in cardiac PET.

PMID- 28497417
TI  - Purinergic P2X7 receptor functional genetic polymorphisms are associated with the
      susceptibility to osteoporosis in Chinese postmenopausal women.
AB  - Osteoporosis (OP) is a major public health problem worldwide. Genetic factors are
      considered to be major contributors to the pathogenesis of OP. The purinergic
      P2X7 receptor (P2X7R) has been shown to play a role in the regulation of
      osteoblast and osteoclast activity and has been considered as an important
      candidate gene for OP. A case-control study was performed to investigate the
      associations of functional single nucleotide polymorphisms (SNPs) in the P2X7R
      gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with
      susceptibility to OP in 400 Chinese OP patients and 400 controls. Results showed
      that rs3751143 was associated with OP; in particular, carriers of the C allele
      and CC/(AC + CC) genotypes were at a higher risk of OP, but no significant
      association of rs2230911, rs7958311, rs1718119, and rs2393799 with OP risk was
      observed. Analysis of the haplotypes revealed one haplotype (rs1718119G
      rs2230911G-rs3751143C) that appeared to be a significant "risk" haplotype with
      OP. The rs3751143 polymorphism was associated with osteoclast apoptosis; ATP
      induced caspase-1 activity of osteoclasts with AC and CC genotypes is lower than
      that of osteoclasts with AA genotype in vitro. The findings suggest that the
      P2X7R rs3751143 functional polymorphism might contribute to OP susceptibility in
      Chinese postmenopausal women.

PMID- 28497419
TI  - Gender Differences in the Presentation of Observable Risk Indicators of Problem
      Gambling.
AB  - In many countries where gambling is legalised, there has been a strong public
      policy focus on the need for strategies to reduce gambling related harm. These
      have often included policies requiring staff in gambling venues to identify
      and/or assist people who might be experiencing gambling-related harm. To
      facilitate this process, researchers have developed visible behavioural
      indicators that might be used to profile potentially problematic gambling. Few of
      these studies have, however, examined whether such indicators or 'warning signs'
      might differ between men and women. In this study, we describe the results of an
      analysis of data drawn from 1185 fortnightly gamblers that included 338 problem
      gamblers as classified by the Problem Gambling Severity Index. Indicators of
      problem gambling were similar between males and females with a few key
      exceptions. Indicators reflecting emotional distress were more commonly reported
      by females with gambling problems, whereas problem gambling males were more
      likely to display aggressive behaviour towards gambling devices and others in the
      venue. Amongst males, signs of emotional distress as well as attempts to conceal
      their presence in venues from others most strongly differentiated between problem
      and non-problem gamblers. Amongst females, signs of anger, a decline in grooming
      and those attempts to access credit were the most distinguishing indicators.
      These findings have implications for the refinement of identification policies
      and practices.

PMID- 28497420
TI  - The role of high airway pressure and dynamic strain on ventilator-induced lung
      injury in a heterogeneous acute lung injury model.
AB  - BACKGROUND: Acute respiratory distress syndrome causes a heterogeneous lung
      injury with normal and acutely injured lung tissue in the same lung. Improperly
      adjusted mechanical ventilation can exacerbate ARDS causing a secondary
      ventilator-induced lung injury (VILI). We hypothesized that a peak airway
      pressure of 40 cmH2O (static strain) alone would not cause additional injury in
      either the normal or acutely injured lung tissue unless combined with high tidal
      volume (dynamic strain). METHODS: Pigs were anesthetized, and heterogeneous acute
      lung injury (ALI) was created by Tween instillation via a bronchoscope to both
      diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure
      release ventilation was used to precisely regulate time and pressure at both
      inspiration and expiration. Animals were separated into two groups: (1) over
      distension + high dynamic strain (OD + HDS, n = 6) and (2) over-distension + low
      dynamic strain (OD + LDS, n = 6). OD was caused by setting the inspiratory
      pressure at 40 cmH2O and dynamic strain was modified by changing the expiratory
      duration, which varied the tidal volume. Animals were ventilated for 6 h
      recording hemodynamics, lung function, and inflammatory mediators followed by an
      extensive necropsy. RESULTS: In normal tissue (NT), OD + LDS caused minimal
      histologic damage and a significant reduction in BALF total protein (p < 0.05)
      and MMP-9 activity (p < 0.05), as compared with OD + HDS. In acutely injured
      tissue (ALIT), OD + LDS resulted in reduced histologic injury and pulmonary edema
      (p < 0.05), as compared with OD + HDS. CONCLUSIONS: Both NT and ALIT are
      resistant to VILI caused by OD alone, but when combined with a HDS, significant
      tissue injury develops.

PMID- 28497421
TI  - Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in
      sepsis.
AB  - OBJECTIVE: Glomerular podocytes are injured in sepsis. We studied, in a sepsis
      patient, whether microRNAs (miRNAs) play a role in the podocyte injury. METHODS:
      Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration
      barrier function of podocyte was analyzed with albumin influx assay. Nephrin
      level was analyzed with reverse transcription polymerase chain reaction (RT-PCR)
      and western blot. MiRNAs were detected using miRNAs PCR Array and in situ
      hybridization. MiRNA target sites were evaluated with luciferase reporter assays.
      RESULTS: LPS impaired the filtration barrier function of podocytes. MiR-128 level
      was decreased and miR-21 level was increased in podocytes in vitro and in the
      sepsis patient. The decrease in miR-128 was sufficient to induce the loss of
      nephrin and the impairment of filtration barrier function, while the increase of
      miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN)
      were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced
      Snail expression, and the increased miR-21 stabilized Snail by regulating the
      PTEN/Akt/GSK3beta pathway. Supplementation of miR-128 and inhibition of miR-21
      suppressed Snail expression and prevented the podocyte injury induced by LPS.
      CONCLUSION: Our study suggests that decreased miR-128 and increased miR-21
      synergistically cause podocyte injury and are the potential therapeutic targets
      in sepsis.

PMID- 28497422
TI  - Utility of urinary circulating tumor DNA for EGFR mutation detection in different
      stages of non-small cell lung cancer patients.
AB  - PURPOSE: Non-invasive methods of molecular profiling for non-small cell lung
      cancer (NSCLC) are useful for monitoring disease progression. The aim of the
      current study was to ascertain if transrenal DNA is sensitive for clinical
      correlation and EGFR detection in NSCLC patients. METHODS: 160 patients at
      various stages of the disease participated and samples were collected
      prospectively at 2-month intervals. A baseline sample was taken before treatment
      commencement. To ascertain the sensitivity of transrenal DNA, we compared its
      results with plasma DNA. ddPCR was used to profile the urine and blood samples
      for key EGFR mutations. RESULTS: Using tumor tissues as references, our study
      showed good concordance in EGFR mutations with transrenal DNA before treatment.
      Results were highly matching in late-stage NSCLC patients, with stage III/IV
      patients yielding an agreement of more than 90%. The assay was also sensitive to
      detect early-stage patients after surgical procedures. Profiles were highly
      concordant with results derived from plasma DNA, demonstrating the specificity of
      transrenal DNA assays. Serial monitoring of these patients showed stable
      molecular signatures and correlated to different treatments. Survival analysis
      showed good prognostic utility for late-stage patients with high transrenal DNA
      variations and patients that acquired T790M mutation. CONCLUSION: The study
      demonstrated the feasibility of using transrenal DNA in mutation profiling for
      different stages of NSCLC patients. It highlights the importance of continual
      monitoring and has potential clinical utility in the clinical management of
      NSCLC.

PMID- 28497423
TI  - Validation of the prognostic value of new sub-stages within the AJCC 8th edition
      of non-small cell lung cancer.
AB  - BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC)
      staging system for non-small cell lung cancer (NSCLC) has been released. The
      current study tried to validate the prognostic significance of the new system
      among patients registered within the surveillance, epidemiology and end results
      (SEER) database. METHODS: SEER database (2010-2013) has been accessed through
      SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the
      collaborative stage descriptions. Overall and lung cancer-specific survival
      analyses according to both 7th and 8th editions were conducted through Kaplan
      Meier analysis and multivariate analysis was conducted through a Cox proportional
      hazard model. RESULTS: A total of 127,096 patients with NSCLC were identified in
      the period from 2010 to 2013. For overall survival assessment according to the
      8th edition, P values for all pair-wise comparisons among different stages were
      significant (<0.0001) except for the comparisons between stage IB and IIA (P =
      0.146); stage IIA and IIB (P = 0.165). For lung cancer-specific survival
      according to the 8th edition, P values for all pair-wise comparisons among
      different stages were significant (<0.001). Among patients with stage I disease,
      multivariate analysis for factors affecting overall and lung cancer-specific
      survival among patients with stage I disease was conducted. The following factors
      were associated with worse overall and lung cancer-specific survival: age >=70
      years, more advanced stage, male gender, squamous histology, no surgery and no
      radiotherapy (P < 0.0001 for all factors). CONCLUSION: This SEER analysis
      supports the prognostic significance of the added sub-stages described within
      AJCC 8th edition stages I and III. Further work is needed to incorporate
      molecular markers and personalize the future editions of the AJCC staging system.

PMID- 28497424
TI  - Validation of SDM-Q-Doc Questionnaire to measure shared decision-making
      physician's perspective in oncology practice.
AB  - OBJECTIVE: The aim of this study was to analyze the psychometric properties of
      the Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) in a
      sample of medical oncologists who provide adjuvant treatment to patients with non
      metastatic resected cancer and the correlations between the total SDM-Q-Doc score
      and physician satisfaction with the information provided. METHODS: Prospective,
      observational and multicenter study in which 32 medical oncologists and 520
      patients were recruited. The psychometric properties, dimensionality, and factor
      structure of the SDM-Q-Doc were assessed. RESULTS: Exploratory factor analyses
      suggested that the most likely solution was two-dimensional, with two correlated
      factors: one factor regarding information and another one about treatment.
      Confirmatory factor analysis based on cross-validation showed that the fitted two
      dimensional solution provided the best fit to the data. Reliability analyses
      revealed good accuracy for the derived scores, both total and sub-scale, with
      estimates ranging from 0.81 to 0.89. The results revealed significant
      correlations between the total SDM-Q-Doc score and physician satisfaction with
      the information provided (p < 0.01); between information sub-scale scores (factor
      1) and satisfaction (p < 0.01), and between treatment sub-scale scores (factor 2)
      and satisfaction (p < 0.01). Medical oncologists of older age and those with more
      years of experience showed more interest in the patient preferences (p = 0.026
      and p = 0.020, respectively). Patient age negatively correlated with SDM
      information (p < 0.01) and physicians appear to provide more information to young
      patients. CONCLUSION: SDM-Q-Doc showed good psychometric properties and could be
      a helpful tool that examines physician's perspective of SDM and as an indicator
      of quality and satisfaction in patients with cancer.

PMID- 28497425
TI  - The next frontier in critical care guidelines: rapid and trustworthy
      recommendations.

PMID- 28497426
TI  - A systematic review of vasopressor blood pressure targets in critically ill
      adults with hypotension.
AB  - PURPOSE: Clinicians must balance the risks from hypotension with the potential
      adverse effects of vasopressors. Experts have recommended a mean arterial
      pressure (MAP) target of at least 65 mmHg, and higher in older patients and in
      patients with chronic hypertension or atherosclerosis. We conducted a systematic
      review of randomized-controlled trials comparing higher vs lower blood pressure
      targets for vasopressor therapy administered to hypotensive critically ill
      patients. METHODS: We searched MEDLINE(r), EMBASETM, and the Cochrane Central
      Register of Controlled Trials for studies of higher vs lower blood pressure
      targets for vasopressor therapy in critically ill hypotensive adult patients. Two
      reviewers independently assessed trial eligibility based on titles and abstracts,
      and they then selected full-text reports. Outcomes, subgroups, and analyses were
      prespecified. We used GRADE (Grading of Recommendations Assessment, Development
      and Evaluation) to rate the overall confidence in the estimates of intervention
      effects. RESULTS: Of 8001 citations, we retrieved 57 full-text articles and
      ultimately included two randomized-controlled trials (894 patients). Higher blood
      pressure targets were not associated with lower mortality (relative risk [RR],
      1.05; 95% confidence interval [CI], 0.90 to 1.23; P = 0.54), and neither age (P =
      0.17) nor chronic hypertension (P = 0.32) modified the overall effect.
      Nevertheless, higher blood pressure targets were associated with a greater risk
      of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38;
      P < 0.01). CONCLUSION: Current evidence does not support a MAP target > 70 mmHg
      in hypotensive critically ill adult patients requiring vasopressor therapy.

PMID- 28497427
TI  - CCCS-SSAI WikiRecs Clinical Practice Guideline: vasopressor blood pressure
      targets in critically ill adults with hypotension.

PMID- 28497429
TI  - Pathogenesis and FDG-PET/CT findings of Epstein-Barr virus-related lymphoid
      neoplasms.
AB  - Epstein-Barr virus (EBV) is one of the most common viruses, infecting more than
      90% of the adult population worldwide. EBV genome is detected in some lymphoid
      neoplasms. Not only their histopathological subtypes, but also their backgrounds
      and their clinical courses are variable. A number of B-cell lymphoproliferative
      disorders associated with the immunocompromised state are related to EBV
      infection. The incidences of these disorders have been increasing along with
      generalization of organ transplantations and use of immunosuppressive treatments.
      Furthermore, some EBV-positive lymphoma can also occur in immunocompetent
      patients. While evaluating patients with generalized lymphadenopathy of unknown
      cause by positron emission tomography/computed tomography with 2-deoxy-2
      [18F]fluoro-D-glucose (FDG-PET/CT), the possibility of lymphoid neoplasms should
      be considered in some patients, and a careful review of the background and
      previous history of the patients is necessary. In this review article, we
      describe the pathogenesis of EBV-related lymphoid neoplasms and then present FDG
      PET/CT images of representative diseases. In addition, we also present a review
      of other EBV-related diseases, such as infectious mononucleosis and
      nasopharyngeal carcinoma.

PMID- 28497428
TI  - CCCS-SSAI WikiRecs Clinical Practice Guideline: vasopressors in early traumatic
      shock.

PMID- 28497430
TI  - Erratum to: Comparative evaluation of the algorithms for parametric mapping of
      the novel myocardial PET imaging agent 18F-FPTP.

PMID- 28497431
TI  - Effect of catheter-based renal denervation on left ventricular function, mass and
      (un)twist with two-dimensional speckle tracking echocardiography.
AB  - BACKGROUND: Speckle tracking echocardiography (STE) is an echocardiography
      modality that is able to measure left ventricular (LV) characteristics, including
      rotation, strain and strain rate. Strain measures myocardial fibre contraction
      and relaxation. This study aims to assess the effect of renal sympathetic
      denervation (RDN) on functional myocardial parameters, including STE, and to
      identify potential differences between responders and non-responders. METHODS:
      The study population consisted of 31 consecutive patients undergoing RDN in the
      context of treatment for resistant hypertension. Patients were included between
      December 2012 and June 2014. Transthoracic echocardiography and speckle tracking
      analysis was performed at baseline and at 6 months follow-up. RESULTS: The study
      population consisted of 31 patients with treatment-resistant hypertension treated
      with RDN (mean age 64 +/- 10 years, 15 men). The total study population could be
      divided into responders (n = 19) and non-responders (n = 12) following RDN. RDN
      reduced office blood pressure by 18.9 +/- 26.8/8.5 +/- 13.5 mmHg (p < 0.001). A
      significant decrease was seen in LV posterior wall thickness (LVPWd) (0.47 +/-
      1.0 mm; p = 0.020), without a significant change in the LV mass index (LVMI). In
      the total cohort, only peak late diastolic filling velocity (A-wave velocity)
      decreased significantly by 5.3 +/- 13.2 cm/s (p = 0.044) and peak untwisting
      velocity decreased significantly by 14.5 +/- 28.9 degrees /s (p = 0.025).
      CONCLUSION: RDN reduced blood pressure and significantly improved functional
      myocardial parameters such as A-wave velocity and peak untwisting velocity in
      patients with treatment-resistant hypertension, suggesting a potential beneficial
      effect of RDN on myocardial mechanics.

PMID- 28497432
TI  - Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting
      Antiviral Use.
AB  - Multiple direct-acting antiviral (DAA)-based regimens are currently approved that
      provide one or more interferon-free treatment options for hepatitis C virus (HCV)
      genotypes (G) 1-6. The choice of a DAA regimen, duration of therapy, and use of
      ribavirin depends on multiple viral and host factors, including HCV genotype, the
      detection of resistance-associated amino acid (aa) substitutions (RASs), prior
      treatment experience, and presence of cirrhosis. In regard to viral factors that
      may guide the treatment choice, the most important is the infecting genotype
      because a number of DAAs are genotype-designed. The potency and the genetic
      barrier may also impact the choice of treatment. One important and debated
      possible virologic factor that may negatively influence the response to DAAs is
      the presence of baseline RASs. Baseline resistance testing is currently not
      routinely considered or recommended for initiating HCV treatment, due to the
      overall high response rates (sustained virological response >90%) obtained.
      Exceptions are patients infected by HCV G1a when initiating treatment with
      simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to
      daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in
      sites of resistance. On the basis of these observations, first-line strategies
      should be optimized to overcome treatment failure due to HCV resistance.

PMID- 28497433
TI  - Marine protected areas in Costa Rica: How do artisanal fishers respond?
AB  - Costa Rica is considering expanding their marine protected areas (MPAs) to
      conserve marine resources. Due to the importance of households' responses to an
      MPA in defining the MPA's ecological and economic outcomes, this paper uses an
      economic decision framework to interpret data from near-MPA household surveys to
      inform this policy discussion. The model and data suggest that the impact of
      expanding MPAs relies on levels of enforcement and on-shore wages. If larger near
      shore MPAs can produce high wages through increased tourism, MPA expansions could
      provide ecological benefits with low burdens to communities. Due to distance
      costs and gear investments, however, MPAs farther off-shore may place high
      burdens on off-shore fishers.

PMID- 28497434
TI  - Thalassemia and hemoglobinopathies in an ethnic minority group in Central
      Vietnam: implications to health burden and relationship between two ethnic
      minority groups.
AB  - Thalassemia is a genetic condition that can result in long and expensive
      treatments, and severe thalassemia may lead to death if left untreated. Couples
      contributing two genes for thalassemia place their children at particular risk
      for severe thalassemia. Gene frequency of thalassemia varies in Vietnam, but
      presents remarkably high levels among some ethnic minority groups. Limited
      information about thalassemia frequency makes prevention and control of
      thalassemia difficult. This study aimed to determine gene frequency of certain
      types of thalassemia among 390 women of reproductive age of the Ta-Oi ethnic
      minority. Hemoglobin and DNA analyses were carried out to diagnose thalassemia
      and hemoglobinopathies. Of the total participants, 56.1% (95% CI = 51.1-61.1)
      carried thalassemia genes. A remarkably high frequency of hemoglobin Constant
      Spring (Hb CS) of 23.8% (95% CI = 19.7-28.4) was noted. The frequency of alpha+
      thalassemia (-3.7 kb deletion) was 26.4% (95% CI = 22.1-31.1), while hemoglobin E
      (Hb E) and hemoglobin Pakse (Hb Ps) were identified at frequencies of 14.6 (95%
      CI = 11.2-18.5) and 2.6% (95% CI = 1.4-5.0), respectively. Further analysis of
      alpha-globin gene haplotype revealed the same Hb CS haplotype (+ - M + + -) as of
      the Co-Tu minority, a neighboring minority of the Ta-Oi, indicating that these
      two minorities may share the same ancestors. This information will be helpful for
      further studies in population genetics, as well as the development prevention and
      control program in the region.

PMID- 28497435
TI  - Genetic Dimension of Intervertebral Disc Degeneration: Polymorphism of Matrix
      Metalloproteinase 1 and 3 in the North Iranian Population.
AB  - AIM: The etiology of intervertebral disc degeneration is still vague and both
      genetic and environmental factors are assumed as the main causes. One of the
      proposed genetic factors is the polymorphism of matrix metalloproteinases (MMPs)
      genes. The aim of this study was to explore the relationship between two
      polymorphisms (MMP-1-755 T/G [rs498186] and MMP-3 A/C [rs632478]) and disc
      degeneration. MATERIAL AND METHODS: We performed a case-control study on 130
      cases with intervertebral disc degeneration confirmed by magnetic resonance
      imaging (MRI) and 210 healthy individuals. The Schneiderman criterion was used to
      determine the severity of the disc degeneration. Blood samples were collected
      from the participants. The genotyping was performed by the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratios
      and 95% CIs were determined as measures of the strength of association between
      genotypes and disc degeneration. RESULTS: The most frequent intervertebral disc
      degeneration was observed in age range of 31-40 years (43.2%). A significant
      association was found between the MMP-3 polymorphism and disc degeneration (p <
      0.001). The homozygote CC was associated with an increased risk of disc
      degeneration compared with the AA genotype (OR=5.25; 95%CI=2.82-9.77, p < 0.001).
      We did not find any significant association of the MMP-1 polymorphism with disc
      degeneration (p=0.95). CONCLUSION: The MMP-3 [rs632478] polymorphism may
      contribute to susceptibility to disc degeneration. To confirm our findings,
      additional well-designed studies in diverse ethnic populations are required.

PMID- 28497437
TI  - FDA Approves TCH Combination for HER2-Positive Early Breast Cancer.

PMID- 28497436
TI  - Factors Related to the Development of Shunt-Dependent Hydrocephalus Following
      Subarachnoid Hemorrhage in the Elderly.
AB  - AIM: Surgical procedures for aneurysmal subarachnoid hemorrhage (SAH) are
      increasing among the elderly as the population ages. Chronic shunt-dependent
      hydrocephalus is a recognized complication of SAH. The aim of this study was to
      identify predictive factors for the development of shunt-dependent hydrocephalus
      among elderly patients with SAH. MATERIAL AND METHODS: We retrospectively studied
      878 patients, including 275 patients ? 65 years old, with SAH treated between
      2005 and 2015 to identify factors contributing to the development of shunt
      dependent hydrocephalus. The relationships between shunt-dependent hydrocephalus
      and the causative factors were analyzed using univariate and multivariate
      analysis; the causative factors were based on the results of previous studies.
      RESULTS: In the 878 patients with SAH, there was a significant difference in the
      incidence of shunt-dependent hydrocephalus between patients < 65 years old and
      those ? 65 years old (p=0.021). In the 275 patients ? 65 years old, the following
      were associated with shunt-dependent hydrocephalus on univariate analysis: 1)
      Hunt and Hess grade (p=0.005), 2) Fisher grade (p < 0.001), 3) intraventricular
      hemorrhage (p < 0.001), 4) acute hydrocephalus (p=0.003), 5) aneurysm location
      (p=0.001), and 6) external ventricular drain placement (p < 0.001). On
      multivariate analysis, only 1) intraventricular hemorrhage (p < 0.001) and 2) a
      ruptured aneurysm located in the distal posterior circulation (p=0.014) were
      related to an increased risk for the development of shunt-dependent
      hydrocephalus. CONCLUSION: Evaluating risk factors can help identify patients at
      high risk of developing shunt-dependent hydrocephalus. Identifying these risk
      factors may help neurosurgeons to provide optimal therapy and improve outcomes in
      patients with SAH.

PMID- 28497438
TI  - A qualitative comparison of ten tissue clearing techniques.
AB  - The understanding of spatially complex biological systems is greatly aided by the
      availability of high resolution information on their tissue architecture, as is
      provided by optical sectioning microscopy like confocal and light sheet
      microscopy. In addition, genetically encoded fluorescent reporter proteins reveal
      tissue architecture without the need for staining procedures. Owing to opacity
      caused by scattering and absorption, light microscopy in tissue is limited to
      thin tissue layers of a few micrometers traditionally provided by histological
      sections. Aiming to allow deeper imaging, during the last decade massive efforts
      to develop tissue clearing protocols produced a flurry of novel clearing
      techniques for whole organ visualization, now available to microscopists. In
      particular, new tissue clearing methods were developed that avoid the use of
      organic solvents, aiming to retain the integrity of genetically encoded
      fluorescent proteins. So far, these methods have not been directly compared and
      selection of the right technique can be a non-trivial task. Here, we have aimed
      to compare different tissue clearing approaches side by side in a standardized
      manner. We provide qualitative data on their clearing capability of mouse brain,
      lung, heart, kidney and muscle, as well as embryos and fetuses at the
      developmental stages E10.5, E12.5 and E15.5 and discuss possible applications.

PMID- 28497439
TI  - [Barcelona Test for Intellectual Disability: a new instrument for the
      neuropsychological assessment of adults with intellectual disability].
AB  - INTRODUCTION: Neuropsychological assessment in individuals with intellectual
      disability is of utmost importance in order to determine the cognitive deficits
      underlying brain dysfunction and limiting intellectual functioning and adaptive
      behavior. However, no neuropsychological batteries in Spanish language have been
      created and validated for this population. AIM: To adapt the 'programa integrado
      de exploracion neuropsicologica-test Barcelona' and to validate the new version,
      the Barcelona Test for Intellectual Disability (TB-DI). To create normative data
      for its clinical use. SUBJECTS AND METHODS: The original test was modified based
      on data from a pilot sample of 65 individuals with intellectual disability. In
      order to study the psychometric properties of the TB-DI, it was administered to a
      sample of 170 individuals with intellectual disability and to a group of 60
      individuals without it. The relevant variables for stratification of normative
      data were determined by means of regression models. RESULTS: The TB-DI was
      finally composed by 67 subtests grouped in eight cognitive domains and it showed
      good psychometric properties. Normative data were created for five groups taking
      into account intellectual disability level, age and acquired curricular
      competence. These data were organized in percentiles in a way that allows the
      creation of cognitive profiles in the clinical and experimental fields.
      CONCLUSION: The TB-DI constitutes a tool of high applicability in the population
      with intellectual disability. It shows adequate validity and reliability, and it
      has good psychometric properties. The cognitive profiles obtained by the TB-DI
      will provide valuable information for the treatment of adult adults with mild and
      moderate intellectual disability.

PMID- 28497440
TI  - [Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine
      clinical practice].
AB  - INTRODUCTION: Fingolimod is a selective immunosuppressant that targets the S1P
      receptor, and is indicated in the treatment of aggressive relapsing-remitting
      multiple sclerosis (RRMS) and following treatment failure with first-order drugs.
      AIM: To investigate the safety and effectiveness of fingolimod under the
      conditions of routine clinical practice. PATIENTS AND METHODS: We conducted an
      observational study with prospective follow-up of patients with RRMS who received
      fingolimod from January 2011 until February 2014. Data assessed were the
      annualised relapse rate (ARR), disability measured by the Expanded Disability
      Status Scale (EDSS), magnetic resonance activity and the appearance of side
      effects. RESULTS: Our sample consisted of 122 patients, 79.5% of them females and
      with a mean age of 26.8 years. They were classified, according to the last
      treatment received, as being: naive (aggressive RRMS; n = 17), previous treatment
      failure (n = 67) and withdrawal of natalizumab due to risk of progressive
      multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 +/- 15.9
      months, the ARR and the appearance of new lesions with gadolinium enhancement
      were reduced in both the naive and the previous treatment failure groups. There
      were no differences between the various subgroups as regards the progression of
      EDSS or the time elapsed until the first attack or treatment failure. The risk of
      treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p =
      0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022).
      CONCLUSIONS: Fingolimod is an effective and well-tolerated drug under conditions
      of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal
      bands is predictive of a poor response to fingolimod.

PMID- 28497441
TI  - [Cryptogenic stroke in a young patient with heart disease and kidney failure].
AB  - INTRODUCTION: Fabry's disease is an infrequent metabolic pathology linked to the
      X chromosome which causes a wide variety of signs and symptoms. CASE REPORT: A 39
      year-old male who was admitted to our stroke unit with right-side hemiparesis (1
      + 0) and dysarthria (1). The score on the National Institute of Health Stroke
      Scale was 2. The patient presented angiokeratomas in both thighs. A computerised
      axial tomography scan of the head showed left thalamic acute infarction. The
      duplex scan of the supra-aortic trunks was normal, and the transcranial Doppler
      reflected a generalised increase in the pulsatility indices. Transthoracic
      echocardiography showed left ventricular hypertrophy and left atrial dilatation.
      He was discharged five days later, with antiaggregating medication but
      asymptomatic. The prolonged Holter-electrocardiogram recording showed paroxysmal
      atrial fibrillation. One notable value in the urine analysis was microalbuminuria
      of 281 mg/L. In view of the multi-organic involvement and the family history, a
      study for Fabry's disease was performed. Activity of the enzyme alpha
      galactosidase A was diminished, and the presence of a mutation in the GLA gene
      was found. The patient's brother, who suffered from kidney failure and atrial
      fibrillation, was positive for this mutation. The patient is on treatment with
      agalsidase beta. CONCLUSIONS: Fabry's disease must be suspected in young males
      with heart disease, stroke or peripheral neuropathy, skin lesions, kidney failure
      and a history of cases in the family. Hormone replacement therapy must be
      established at an early stage, as it can improve the prognosis.

PMID- 28497443
TI  - [XXXIV Reunion Anual de la Sociedad Valenciana de Neurologia. Communications].

PMID- 28497442
TI  - [Myths and evidence on the use of botulinum toxin: spasticity in adults and in
      children with cerebral palsy].
AB  - INTRODUCTION: Spasticity is a medical problem with a high incidence that
      significantly impact on the quality of life of patients and their families. AIM:
      To analyze and to answer different questions about the use of botulinum toxin
      type A (BTA) in our clinical practice. DEVELOPMENT: A group of experts in
      neurology develop a list of topics related with the use of BTA. Two big groups
      were considered: spasticity in adults and in children with cerebral palsy. A
      literature search at PubMed for English, French, and Spanish language articles
      published up to June 2016 was performed. The manuscript was structured as a
      questionnaire that includes those questions that, according to the panel opinion,
      could generate more controversy or doubt. The initial draft was reviewed by the
      expert panel members to allow for modifications, and after subsequent revisions
      for achieving the highest degree of consensus, the final text was then validated.
      Different questions about diverse aspects of spasticity in adults, such as
      methods for evaluating spasticity, infiltration techniques, doses, number of
      infiltration points, etc. Regarding spasticity in children with cerebral palsy,
      the document included questions about minimum age of infiltration, methods of
      analgesia, etc. CONCLUSIONS: This review is a tool for continuous training for
      neurologist and rehabilitation specialist and residents of both specialties,
      about different specific areas of the management of BTA.

PMID- 28497444
TI  - [Lance-Adams syndrome after infective endocarditis].

PMID- 28497445
TI  - [Value of molecular imaging to examine the brain].

PMID- 28497446
TI  - The role of water-jet dissection in improving erectile function and urinary
      continence after nerve-sparing prostatectomy.
AB  - OBJECTIVES: The aim of this study was to assess erectile function (EF) and
      urinary continence (UC) recovery after nerve-sparing retropubic radical
      prostatectomy (NS-RRPE) and nerve-sparing laparoscopic radical prostatectomy (NS
      LRPE) depending on the neurovascular bundle (NVB) dissection technique used.
      METHODS: Twenty-four hour pad test was used to assess the degree of postoperative
      UC 1, 6 and 12 months after the surgery. For the purpose of EF assessment,
      International Index of Erectile Function-5 (IIEF-5) questionnaire was used. In
      addition, EF recovery assessment included the time needed to achieve a successful
      sexual intercourse with or without Inhibitors Phosphodiesterase 5 (IPDE5). A
      successful sexual intercourse was defined as an ability to achieve a strong
      erection enough for penetration and maintain erection for a long time, throughout
      the intercourse. Assessment was performed before the surgery and 8 and 6 months
      after the surgery. RESULTS: In the patient group with BNS + water jet dissection
      (WJD), the IIEF-5 score was considerably higher 8 weeks after the surgery (by 2.8
      points) (r = 0.02). In 6 months, the difference between the group become more
      significant and reached 3.5 points (p = 0.01). Three months after urethral
      catheter removal, majority (95%) of patients in the NS-RPE + WJD group had no
      urinary incontinence (UI). For standard NS-RPE, that figure was 87%. Mild stress
      UI was observed in 5% of patients after NS-RPE + WJD and in 13% of patients after
      NS-RPE. Six months after urethral catheter removal, no significant differences in
      UC assessment were observed in the two groups. CONCLUSIONS: The implementation of
      WJD of NVB in clinical practice has made it possible to considerably improve the
      quality of life for postoperative patients due to good outcomes in terms of early
      UC and EF recovery.

PMID- 28497447
TI  - Holmium laser enucleation of the prostate (HoLEP) for small, large and giant
      prostatic hyperplasia: tips and tricks.
AB  - INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) allows to treat
      extremely large prostates (>200 cm3). The aim of the study was to compare the
      efficiency of HoLEP for prostates of different sizes. METHODS: Four hundred and
      fifty-nine patients were divided into three groups: group 1 included 278 patients
      (<100 cm3); group 2 included 169 patients (100-200 cm3); group 3 included 12
      patients (>200 cm3). RESULTS: The duration of enucleation in group 1 was 56.5 +/-
      10.7 min; in group 2 was 96.4 +/- 24.9 min; in group 3 was 120.9 +/- 35 min. The
      duration of morcellation in group 1 was 37.5 +/- 7.3 min; in group 2 was 63.3 +/-
      11.2 min; in group 3 was 84.0 +/- 25.6 min. The enucleation efficiency in group 3
      (1.70 g/min) was higher (p<0.05) than in group 1 (1.05 g/min) and group 2 (1.23
      g/min). Morcelation efficiency was lower in groups 1 and 2 (1.58 and 1.87 g/min,
      respectively) than in group 3 (2.45 g/min) (p<0.05).Follow-up period lasted 18
      months. There were no significant differences (p>0.05) in International Prostate
      Symptom Score, Qmax, quality of life and postvoid residual volume for 1, 3, 6, 12
      and 18 months after surgery. CONCLUSIONS: HoLEP is a safe, highly efficacious and
      a size-independent procedure.

PMID- 28497448
TI  - Healing of spongiosus-cutaneous fistula with hyperbaric Oxygen Therapy (HBOT): a
      case report.
AB  - INTRODUCTION: We present a case of a spongiosus-cutaneous fistula in a 39-year
      old man with recurrent episodes of cutaneous abscess in dorsal middle third penis
      (5 * 3 cm) treated with Hyperbaric Oxygen Therapy (HBOT). CASE REPORT: After
      emptying nodular abscess, the patient was noncompliant for further surgery.
      Therefore, it was suggested the association between HBOT and antibiotic therapy.
      HBOT is carried out in a hyperbaric room, where the internal pressure is
      increased (compression phase) by entering compressed air up to 283.71 kPa in
      about 10 minutes. Every HBOT cycle lasted 24 days in which the patient had been
      taking Amoxicillin/Clavulanic Acid 875 mg/125 mg 3 tabs/day and
      Sulfamethoxazole/Trimethoprim 160 mg/800 mg 2 tabs/day for 2 weeks. At the end of
      the treatment, a penile magnetic resonance imaging and an ultrasonography were
      executed and they evidenced a complete remission of the lesion. In the subsequent
      22 months, there was no recurrence. CONCLUSIONS: Our results suggest that HBOT is
      an effective treatment for chronic wounds, including a spongiosus-cutaneous
      fistula of unknown cause, when used in combination with conventional standard
      therapy or further interventions. At present time, the gold standard remains
      surgery; nevertheless, our experience with HBOT may stimulate its use in clinical
      trials.

PMID- 28497449
TI  - Percutaneous US-guided renal cryoablation using 3D modeling.
AB  - INTRODUCTION: The article describes the first experience of performing
      percutaneous ultrasound (US)-guided cryoablation of renal tumor and assesses the
      safety and short-term results of treatment. MATERIALS AND METHODS: Twelve
      patients were subjected to US-guided cryoablation of renal tumor in 2015. The
      tumor size in 11 patients was up to 3.0 cm (T1a); in one female patient, 4.5 cm
      (T1b). Tumors were assessed according to the PADUA score. In eight patients, it
      was 6-7 (low); in three patients, 8-9 (average); in one, 10 (high). All the
      patients underwent US examination using a FlexFocus 800 apparatus with convex
      abdominal transducers. Before surgery and 6 months later, all the patients
      underwent renal Doppler US and contrast-enhanced computed tomography. RESULTS:
      The average cryoablation time was 60 min. Seven operations were performed under
      spinal anesthesia and five operations under local anesthesia. The follow-up
      period lasted 8 months on average. According to the ultrasonography and Doppler
      findings, after 6 months, the tumor (T1a) in 11 patients reduced in size by an
      average of 7-8 mm and had no blood supply.T1b patient's mass size reduces from
      4.5 to 3.7 cm; however, a 1.5 cm area with a high attenuation gradient of the
      contrast medium was visualized. Later, the patient was subjected to laparoscopic
      renal resection. Histological finding revealed clear-cell carcinoma. CONCLUSIONS:
      We consider percutaneous US-guided cryoablation as a method of choice for
      patients with stage T1a renal tumor localized on the posterior or lateral surface
      in the inferior or middle segment without sinus involvement and PADUA <9.

PMID- 28497450
TI  - The role of hemodialysis in treatment of acute acetic acid poisonings.
AB  - INTRODUCTION: The aim of this study is to show the importance of hemodialysis as
      an active method in treatment of acute acetic acid poisonings. Its main role is
      to support the renal function during the state of the intoxication when patients
      develop acute renal failure. METHODS: We analyzed data from a 10-year period, a
      total of 71 patients who ingested acetic acid, either intentionally or
      accidentally. Patients with a need of hemodialysis (HD) treatment underwent 3- to
      4-hour HD sessions every day or every second day, according to clinical
      assessment, as needed, until recovery of kidney function. RESULTS: In the period
      between 2006 and 2015 at the university clinic for toxicology and urgent internal
      medicine, we hospitalized 6,106 patients with different kinds of intoxication, of
      which 1.162% ingested concentrated acetic acid; 47 patients were female and 24
      were male. The minimal age of patients was 18 and the maximal 74 years. A total
      of 28 (39.43%) of the patients developed acute renal failure and in 10 patients
      (14.08%) we used hemodialysis as a part of the treatment. The maximum number of
      performed sessions in one patient was five and the minimal number of performed
      sessions in one patents was only one session. The use of heparin led to fatal
      bleeding in 4 patients. The mortality rate was 7% and most of the cases resulted
      in fatalities during the first 96 hours after ingestion. CONCLUSIONS: Acetic acid
      poisonings are one of the most dangerous intoxications seen in clinical
      toxicology. The use of hemodialysis in some of the patients who develop acute
      renal failure can be of great importance and it should be put into official
      treatment protocols due to its great number of advantages in renal function
      support.

PMID- 28497451
TI  - Anterior greater trochanteric muscle pedicle bone grafting: a viable graft option
      adjunct to hip osteotomy or fracture surgery.
AB  - INTRODUCTION: The objectives were to evaluate a technique, outcome and
      complications following anterior greater trochanteric with gluteus medius muscle
      pedicle bone graft (AMG) procedure in the treatment of adolescent and active
      adult hip disorders. METHODS: 20 patients (20 hips) with a mean age of 22.7 +/-
      15.6 (range 10.0-63.5) years who had undergone AMG and been followed up more than
      12 months postoperative were retrospectively enrolled in our study. The AMG
      procedure was performed in conjunction with subcapital osteotomy for slipped
      capital femoral epiphysis in 12 and open reduction for fracture/dislocation in 8
      hips. At the most recent evaluation, patient functional status was rated by the
      Harris Hip Score (HHS) and radiographic changes were graded according to Tonnis
      criteria. Complications were defined as Tonnis grade >2 or hip requiring further
      surgery. Univariate analysis was used to explore factors associated with
      complications. Spearman's rank correlation coefficient was calculated between HHS
      and Tonnis grading. RESULTS: At mean follow-up of 4.4 +/- 2.6 (range 1.1-9.5)
      years, mean HHS was 87.4. Tonnis grading was rated as 0 in 10 hips, 1 in 5 hips,
      2 in 2 hips, and 3 in 3 hips. Avascular necrosis of the femoral head as a
      complication developed in 3 hips (15%). Clinical parameters including age at
      surgery, duration of follow-up and diagnosis were not significantly associated
      with postoperative complications. A negative correlation between HHS and Tonnis
      grade was shown by Spearman's rank correlation (rs = -0.49, p = 0.03).
      CONCLUSIONS: The AMG can be safely recommended as an adjunct bone graft procedure
      when performing anterior open reduction of adolescent and active adult hip
      disorders.

PMID- 28497452
TI  - An attempt to throw light on congenital hip disease terminology and anticipation
      of clinical outcomes when treated with total hip arthroplasty.
AB  - The terminology of the wide spectrum of hip deformities seen during the neonatal,
      infantile and adult life period remains controversial, mainly due to the
      indiscriminate use of the terms dysplasia, subluxation, congenital hip disease,
      developmental hip disease, congenital dislocation, etc. This has a serious
      implication on the anticipation of clinical outcomes, complications and
      comparison of different reconstructive techniques when these patients are treated
      with total hip arthroplasty in adulthood. Journals, specialising in this field,
      should publish homogeneous series (type of the disease, reconstruction technique,
      implants) in order to clarify arguments and anticipate clinical outcomes.

PMID- 28497453
TI  - Trends in total hip arthroplasty in young patients - results from a regional
      register.
AB  - INTRODUCTION: In the United Kingdom, over 83,000 primary total hip arthroplasties
      (THAs) were performed last year, of which 20% are in patients under the age of 60
      years. These patients generally have a longer life expectancy and a higher
      activity level than an older cohort, which may potentially translate to higher
      revision rates. METHODS: We reviewed our Trent regional arthroplasty register to
      assess current surgical practice in younger patients undergoing total hip
      arthroplasty. The results were compared to a previous study published in 2005.
      RESULTS: Between 2010 and 2012, 1,097 primary THAs were performed on patients
      aged 54 or less. There was an equal cohort of males to females with a mean age of
      46 years of patients undergoing THA. Osteoarthritis was the commonest aetiology
      for patients having surgery. Reviewing the components used there were 32
      different femoral and 30 different acetabular types along with 70 different
      combinations of components. There were 608 uncemented THAs, 313 hybrid THRs, 98
      cemented THAs, 67 resurfacing arthroplasties and 11 reverse hybrid THAs.
      DISCUSSION: The majority of implants were uncemented in both femur and acetabulum
      with consultants performing most of the procedures. There is a clear preference
      for uncemented femoral and acetabular fixation in the younger patient, and the
      trend towards uncemented components has increased over the last 10 years amongst
      the same surgeons. There continues to be a wide variety of cup and stem usage
      along with many different combinations of components, with no consensus on the
      ideal combination.

PMID- 28497454
TI  - Efficacy of core decompression for treatment of canine femoral head osteonecrosis
      induced by arterial ischaemia and venous congestion.
AB  - METHODS: 40 healthy mixed-breed dogs were randomly divided into 2 groups,
      arterial ischaemia (AI) and venous congestion (VC), each containing 20 dogs. The
      dogs underwent a procedure where the deep femoral artery or deep femoral vein was
      ligated randomly on the left or right side to establish the femoral head
      osteonecrosis model. 13 dogs from each group, AI and VC, were randomly selected
      for subsequent study. 3 dogs were randomly chosen from each group to receive core
      decompression (CD) every 2 weeks for a total of 4 sessions. RESULTS: The
      development of femoral head osteonecrosis was slightly slowed at each measurement
      time point after CD in the arterial ischaemia (AI) group, but no restoration was
      observed. The venous congestion (VC) group showed a gradually reduced mixed
      signal after CD and exhibited a trend towards restoration. The various VC
      subgroups had significantly improved symptoms compared to the AI subgroups.
      CONCLUSIONS: CD displayed greater treatment efficacy for femoral head
      osteonecrosis caused by VC, but poor efficacy for femoral head osteonecrosis
      caused by AI.

PMID- 28497455
TI  - Hip sonography: background; technique and common mistakes; results; debate and
      politics; challenges.
AB  - Developmental dysplasia of the hip (DDH) is the commonest 'congenital' disease of
      the locomotor system throughout the world. According to the World Health
      Organisation (WHO) Bone & Joint Decade (2000-2010) 10%-15% of patients who are
      under the age of 50 when they require a hip replacement do so because of infant
      hip dysplasia.The background; technique and common mistakes; results; debate and
      politics; and the challenges of infant hip sonography are reviewed.

PMID- 28497456
TI  - Survivorship and complications of total hip arthroplasty in patients with
      dwarfism.
AB  - BACKGROUND: Total hip arthroplasty (THA) is a common procedure used to treat bony
      hip deformities and skeletal dysplasia in dwarfism. These surgeries are often
      more difficult than conventional THA as they may involve malformed joints and
      poor bone quality, and may require smaller prostheses. This study aims to
      investigate whether implant survivorship and revision rates vary among patients
      with and without dwarfism undergoing THA. METHODS: A retrospective case-control
      study was performed for 102 THAs completed between 1997 and 2014 in patients
      under the height threshold of 147.32 cm. This cohort was matched 1:1.5 with
      patients of normal height with respect to age, gender, year of surgery, and
      Charlson comorbidities. All cases had a minimum follow-up of 1 year. A chart
      review was performed to identify patient and surgical characteristics, including
      outcomes. Radiographs were assessed for deformity, loosening, and periprosthetic
      fractures among other factors. RESULTS: The 2-, 5-, and 10-year survivorship of
      THA in patients with dwarfism was 92.9%, 92.9%, and 80.7%, respectively; and
      94.4%, 86.4%, and 86.4% for controls, respectively (p = 0.95). The dwarfism
      cohort demonstrated an OR of 3.81 and 3.02 for revision for periprosthetic
      fractures (p = 0.11) and mechanical wear (p = 0.21), respectively. CONCLUSIONS:
      THA in patients with dwarfism achieves comparable results to a non-dwarfism
      population with regards to implant survivorship; however, there is a trend toward
      increased periprosthetic fractures and wear-related failures. Surgeons should be
      aware of this potentially higher risk in this population and take morphological
      differences into account during surgical planning and technique.

PMID- 28497457
TI  - Mitochondrial DNA copy number variation as a potential predictor of renal cell
      carcinoma.
AB  - BACKGROUND: Peripheral blood mitochondrial DNA (mtDNA) copy number alteration has
      been suggested as a risk factor for several types of cancer. The aim of the
      present study was to assess the role of peripheral blood mtDNA copy number
      variation as a noninvasive biomarker in the prediction and early detection of
      renal cell carcinoma (RCC) in a cohort of Egyptian patients. METHODS:
      Quantitative real-time polymerase chain reaction (qPCR) was used to measure
      peripheral blood mtDNA copy numbers in 57 patients with newly diagnosed, early
      stage localized RCC and 60 age- and sex-matched healthy individuals as a control
      group. RESULTS: Median mtDNA copy number was significantly higher in RCC cases
      than in controls (166 vs. 91, p<0.001). Increased mtDNA copy number was
      associated with an 18-fold increased risk of RCC (95% confidence interval: 5.065
      63.9). On receiver operating characteristic curve analysis, it was found that
      mtDNA could distinguish between RCC patients and healthy controls, with 86%
      sensitivity, 80% specificity, 80.3% positive predictive value and 85.7% negative
      predictive value at a cutoff value of 108.5. CONCLUSIONS: Our results showed that
      increased peripheral blood mtDNA copy number was associated with increased risk
      of RCC. Therefore, RCC might be considered as part of a range of potential tumors
      in cases with elevated blood mtDNA copy number.

PMID- 28497458
TI  - Ocular Surface Disease in Patients under Topical Treatment for Glaucoma.
AB  - PURPOSE: To examine the relationship between ocular surface disease (OSD) and
      topical antiglaucoma therapy. METHODS: A total of 211 eyes of 211 patients with
      open-angle glaucoma or ocular hypertension on topical medication were recruited
      over 10 months. Controls were 51 eyes of 51 healthy age- and sex-matched
      volunteers. In each patient, we recorded the intraocular pressure-lowering
      eyedrops used, the number of medications used, and daily and cumulative
      preservative concentrations (PC). Main outcome measures were fluorescein corneal
      staining score (Oxford scale), lower tear meniscus height (LTMH) (spectral-domain
      optical coherence tomography), noninvasive tear film breakup time (NI-TBUT)
      (Oculus Keratograph 5M), and OSD symptom questionnaire index (OSDI). RESULTS:
      Compared to controls, significantly higher OSDI (median [interquartile range]
      10.24 [4.54-18.94] vs 2.5 [0-12.5]; p<0.001) and corneal staining (>=1: 64.93% vs
      32.61%; p<0.001) scores were recorded in the medication group. The NI-TBUT and
      LTMH failed to vary between the groups (p>0.05). A higher daily PC was associated
      with a lower LTMH (R -0.142; p = 0.043). In the medication group, multivariate
      analysis identified correlations between benzalkonium chloride (BAK) (odds ratio
      [OR] 1.56) and BAK plus polyquaternium-containing drops (OR 5.09) or higher OSDI
      (OR 1.06) and abnormal corneal staining test results and between older age (mean
      ratio [MR] 1.05), longer treatment duration (MR 1.02), or corneal staining
      presence (MR 1.22) and a higher OSDI score. CONCLUSIONS: Ocular surface disease
      was more prevalent in the medication group. The main factors impacting OSD were
      drops with preservatives, longer treatment duration, and older age.

PMID- 28497459
TI  - Author's reply to comments to: Visual and anatomic outcomes after conversion to
      aflibercept in neovascular age-related macular degeneration: 12-month results.

PMID- 28497460
TI  - On the QT-interval and death from chloroform.

PMID- 28497461
TI  - ICSI outcome in patients with high DNA fragmentation: Testicular versus
      ejaculated spermatozoa.
AB  - Sperm DNA fragmentation (SDF) has emerged as an important biomarker in the
      assessment of male fertility potential with contradictory results regarding its
      effect on ICSI. The aim of this study was to evaluate intracytoplasmic sperm
      injection (ICSI) outcomes in male patients with high SDF using testicular versus
      ejaculated spermatozoa. This is a prospective study on 36 men with high-SDF
      levels who had a previous ICSI cycle from their ejaculates. A subsequent ICSI
      cycle was performed using spermatozoa retrieved through testicular sperm
      aspiration. Results of the prior ejaculate ICSI were compared with those of the
      TESA-ICSI. The mean (SD) SDF level was 56.36% (15.3%). Overall, there was no
      difference in the fertilization rate and embryo grading using ejaculate and
      testicular spermatozoa (46.4% vs. 47.8%, 50.2% vs. 53.4% respectively). However,
      clinical pregnancy was significantly higher in TESA group compared to ejaculated
      group (38.89% [14 of 36] vs. 13.8% [five of 36]). Moreover, 17 live births were
      documented in TESA group, and only three live births were documented in ejaculate
      group (p < .0001). We concluded that the use of testicular spermatozoa for ICSI
      significantly increases clinical pregnancy rate as well as live-birth rate in
      patients with high SDF.

PMID- 28497462
TI  - Skin hyperpigmentation following intravenous polymyxin B treatment associated
      with melanocyte activation and inflammatory process.
AB  - What is known and objective Polymyxins were widely used until the 1960s; however,
      they fell into disfavour owing to their toxicity. The subsequent growth of
      infections caused by multidrug-resistant Gram-negative bacteria has led to
      renewed use of this class of antimicrobials in clinical practice. Acquired skin
      hyperpigmentation (SH) following intravenous polymyxin B treatment has been
      previously reported, but little is known about its pathogenesis, clinical course
      and treatment. To improve understanding of these issues, we conducted a
      prospective study of adult patients receiving intravenous polymyxin B treatment.
      Methods Patients receiving intravenous polymyxin B treatment were followed
      throughout the course of treatment. Clinical, dermatoscopic, histologic and
      immunohistochemical skin properties of patients who presented with SH were
      studied. Results and discussion Skin hyperpigmentation was noted in 8% of
      patients (n=20/249); however, clinical, dermatoscopic, histologic and
      immunohistochemical examinations were performed only in three patients for whom
      the consent of relatives was obtained. Histologic and immunohistochemical
      findings showed an abundant melanocyte-pigmented dendritic network. Langerhans
      cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for
      an inflammatory process due to polymyxin B use. As polymyxin B causes the release
      of histamine, which is known for its melanogenic effect, it is possible that skin
      darkening is associated with this inflammatory mediator. What is new These
      clinical and dermatoscopic findings contribute to a better understanding of how
      the pigmentary reaction manifests following intravenous polymyxin B treatment.
      Conclusion We concluded that hyperpigmentation due to intravenous polymyxin B
      treatment is associated with an inflammatory process and subsequent melanocyte
      activation. Although the pigmentary disorder neither influences the outcome of
      the therapy nor warrants discontinuation of treatment, it nevertheless
      considerably affects the patient's quality of life.

PMID- 28497463
TI  - Can haematologic parameters be used for differential diagnosis of testicular
      torsion and epididymitis?
AB  - A differential diagnosis of testicular torsion and epididymitis has serious
      importance for testicular health. In emergency conditions, if testicular torsion
      goes unnoticed and epididymo-orchitis is diagnosed, organ loss may occur. This
      study aimed to evaluate the usefulness of haematologic parameters for the
      diagnosis of both testicular torsion and epididymo-orchitis and for differential
      diagnosis of these two diseases. Patients were divided into three groups as those
      undergoing surgery for testicular torsion, those receiving medical treatment for
      epididymitis and a healthy control group. All patients had complete blood counts
      taken with determinations of mean platelet volume (MPV), platelet/lymphocyte
      ratio (PLR), neutrophil/lymphocyte ratio (NLR) and leucocyte counts. These were
      then compared between groups. Leucocyte, MPV and NLR values were higher in both
      the epididymitis and torsion groups compared to the controls (p < .001). Platelet
      counts and PLR were significantly higher in the epididymitis group compared to
      the other two groups (p < .001). Leucocyte, MPV and NLR values may be used in the
      diagnosis of epididymitis and testicular torsion. Platelet counts and PLR appear
      to be useful in differentiating epididymitis from testicular torsion. However,
      there is a need for prospective studies with larger numbers of patients.

PMID- 28497464
TI  - In vivo proton observed carbon edited (POCE) 13 C magnetic resonance spectroscopy
      of the rat brain using a volumetric transmitter and receive-only surface coil on
      the proton channel.
AB  - PURPOSE: In vivo carbon-13 (13 C) MR spectroscopy (MRS) is capable of measuring
      energy metabolism and neuroenergetics, noninvasively in the brain. Indirect (1 H
      [13 C]) MRS provides sensitivity benefits compared with direct 13 C methods, and
      normally includes a 1 H surface coil for both localization and signal reception.
      The aim was to develop a coil platform with homogenous B1+ and use short
      conventional pulses for short echo time proton observed carbon edited (POCE) MRS.
      METHODS: A 1 H-[13 C] MRS coil platform was designed with a volumetric resonator
      for 1 H transmit, and surface coils for 1 H reception and 13 C transmission. The
      Rx-only 1 H surface coil nullifies the requirement for a T/R switch before the 1
      H preamplifier; the highpass filter and preamplifier can be placed proximal to
      the coil, thus minimizing sensitivity losses inherent with POCE-MRS systems
      described in the literature. The coil platform was evaluated with a PRESS-POCE
      sequence (TE = 12.6 ms) on a rat model. RESULTS: The coil provided excellent
      localization, uniform spin nutation, and sensitivity. 13 C labeling of Glu-H4 and
      Glx-H3 peaks, and the Glx-H2 peaks were observed approximately 13 and 21 min
      following the infusion of 1-13 C glucose, respectively. CONCLUSION: A convenient
      and sensitive platform to study energy metabolism and neurotransmitter cycling is
      presented. Magn Reson Med 79:628-635, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 28497465
TI  - Designing 3D selective adiabatic radiofrequency pulses with single and parallel
      transmission.
AB  - PURPOSE: To introduce a method of designing single and parallel transmit (pTx) 3D
      adiabatic pi pulses for inverting and refocusing spins that are insensitive to
      transmit B1 ( B1+) inhomogeneity. THEORY AND METHODS: A 3D adiabatic pulse is
      created by replacing each piece-wise constant element (or sub-pulse) of an
      adiabatic full passage (AFP) by a 2D selective pulse. In this study, the parent
      AFP is an HS1 and each sub-pulse is a 2D pulse derived from a jinc function
      designed using a spiral k-trajectory. Spatial selectivity in the third direction
      is achieved by blipping the slab-selective gradient between sub-pulses, yielding
      a rectangular slab profile identical to that of the parent AFP. The slew-rate
      limited sub-pulse can be undersampled utilizing pTx, thus shortening the overall
      pulse width. Simulations and experiments demonstrate the quality of spatial
      selectivity and adiabaticity achievable. RESULTS: The 3D adiabatic pulse inverts
      and refocus spins in a sharply demarcated cylindrical volume. When stepping RF
      amplitude, an adiabatic threshold is observed above which the flip angle remains
      pi. Experimental results demonstrate that pTx is an effective means to
      significantly improve pulse performance. CONCLUSION: A method of designing 3D
      adiabatic pulses insensitive to B1 inhomogeneity has been developed. pTx can
      shorten these pulses while retaining their adiabatic character. Magn Reson Med
      79:701-710, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 28497466
TI  - Determination of inter-ionic and intra-ionic interactions in a monofluorinated
      imidazolium ionic liquid by a combination of X-ray crystallography and NOE NMR
      spectroscopy.
AB  - We report the very first application of a Transient 1D 1 H{19 F} NOE NMR
      experiment in neat ionic liquids. In comparison with classical 2D HOESY NMR
      spectroscopy, a substantial reduction in measurement time is gained with
      comparable quality and information content of the spectra. In combination with
      classical X-ray crystallography, we have applied this technique for the
      determination of inter-ionic distances (i.e. probabilities of presence) utilizing
      an ionic liquid containing a monofluorinated imidazolium cation. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28497467
TI  - PhotoExam: adoption of an iOS-based clinical image capture application at Mayo
      Clinic.
AB  - BACKGROUND: Mayo Clinic developed an internal iOS-based, point-of-care clinical
      image capture application for clinicians. We aimed to assess the adoption and
      utilization of the application at Mayo Clinic. METHODS: Metadata of 22,784 photos
      of 6417 patients taken by 606 users over 8040 clinical encounters between
      3/1/2015 and 10/31/2015 were analyzed. A random sample of photos from 100
      clinical encounters was assessed for quality using a five-item rubric. Use of
      traditional medical photography services before and after application launch were
      compared. RESULTS: The largest group of users was residents/fellows, accounting
      for 31% of users but only 18% of all photos. Attending physicians accounted for
      29% of users and 30% of photos. Nurses accounted for 14% of users and 28% of
      photos. Surgical specialties had the most users (36% of users), followed by
      dermatology (14% of users); however, dermatology accounted for 54% of all photos,
      and surgery accounted for 26% of photos. Images received an average of 91% of
      possible points on the quality scoring rubric. Most frequent reasons for missing
      points were the location on the body not clearly being demonstrated (19% of
      encounters) and the perspective/scale not being clearly demonstrated (12% of
      encounters). There was no discernible pre-post effect of the application's launch
      on use of traditional medical photography services. CONCLUSIONS: Point-of-care
      clinical photography is a growing phenomenon with potential to become the new
      standard of care. Patient and provider attitudes and the impact on patient
      outcomes remain unclear.

PMID- 28497468
TI  - A case-control study analyzing the association of keloids with hypertension and
      obesity.

PMID- 28497470
TI  - Cancer, ageing, multimorbidity and primary care.
AB  - Cancer care is complex, and made more so by multimorbidity and ageing.
      Multimorbidity affects all stages of cancer care from prevention and early
      detection through to end of life care. The effectiveness of cancer treatments in
      multimorbid patients may not be understood, as many conditions common in older
      people may be exclusion criteria in oncology clinical trials. The interaction
      between pre-existing physical capacity, multiple medical conditions and ageing
      can delay diagnosis, impact on treatments, complicate survivor care, and impact
      on decisions about starting and ceasing treatments. General Practitioners (GPs)
      manages multimorbidity routinely, yet the GP role in comprehensive cancer care is
      limited. Integration of GP management of multimorbidity in conjunction with
      oncology services should improve patient outcomes. Integration of care for these
      patients can educate patients on the minimisation of multimorbidity, develop
      personalised screening plans and contribute to the wholistic management of people
      in the surveillance period. GPs should have a major role in end of life care.
      Integration of general practice and oncology should benefit patient care.

PMID- 28497469
TI  - Prognostic models for identifying adults with intellectual disabilities and
      mealtime support needs who are at greatest risk of respiratory infection and
      emergency hospitalisation.
AB  - BACKGROUND: Among adults with intellectual disabilities (ID), problems with
      eating, drinking and swallowing (EDS), and an associated need for mealtime
      support, are common, with an estimated 15% of adults known to specialist ID
      services requiring mealtime support. We set out to identify which adults with ID
      who receive mealtime support are at an increased risk of respiratory infections
      and emergency hospitalisation related to EDS problems. METHOD: An exploratory,
      prospective cohort study was undertaken in the East of England. At baseline,
      structured interviews with the caregivers of 142 adults with ID and any type of
      mealtime support needs were used to gather information on health and support
      needs over the previous 12 months. These interviews were repeated at follow-up,
      12 months later. The resulting dataset, covering a 24-month period, was analysed
      with logistic regression, using model averaging to perform sensitivity analysis,
      and backwards step-wise variable selection to identify the most important
      predictors. RESULTS: Individuals with a history of respiratory infections (in the
      first year of study), those who had epilepsy and those with caregiver-reported
      difficulty swallowing were most likely to have respiratory infections in the
      second year. Adults with increasing mealtime support needs, epilepsy and/or full
      mealtime support needs (fed mainly or entirely by a caregiver or enterally) were
      at increased risk of emergency hospitalisation for EDS-related problems.
      CONCLUSIONS: Our findings highlight the importance of carefully monitoring health
      issues experienced by adults with ID and EDS problems, as well as their eating,
      drinking and swallowing skills. However, the models developed in this exploratory
      research require validation through future studies addressing the EDS problems
      commonly experienced by adults with ID and their implications for health outcomes
      and quality of life. Further research into the relationship between epilepsy and
      EDS problems would provide much-needed insight into the complex relationship
      between the two areas.

PMID- 28497471
TI  - Clinician perspectives on symptom and quality of life experiences of patients
      during cancer therapies: Implications for eHealth.
AB  - OBJECTIVE: The purpose of this study was to explore clinician experiences with
      cancer symptom and quality of life (SQL) management from diagnosis throughout
      therapy in the ambulatory setting, plus identify preferences for a future SQL
      decision support system. METHODS: Eligible clinicians worked in ambulatory cancer
      care with responsibility for direct patient care. Focus groups were conducted to
      discuss symptom management throughout the treatment experience and features
      desired in a future decision support system. Each group was audio-recorded,
      transcribed, de-identified, and entered into NVivo 9 for analysis. Open and axial
      coding was completed, grouping common concepts into nodes; large constructs among
      the nodes were identified and main messages were synthesized. RESULTS: A total of
      118 clinicians were contacted by email resulting in a final sample of 51
      attending 1 of 9 focus groups. Clinicians described a standard face-to-face
      approach to assessment of SQL, before and throughout therapy. Preparing patients
      for expected symptoms and approaches to management included paper-based patient
      education materials and referrals. Communicating with patients between visits was
      covered in detail, notably use of telephone and email. Future system features
      desired by the clinicians included an electronic, Web-based system with real
      time, trended data, reasonable alerts, and tailored information for patients.
      CONCLUSIONS: Cancer care specialists reported strategies to assess and manage
      cancer SQL in ambulatory care including patient-reported outcome measures,
      contact communication modes, face-to-face interviews, and paper-based patient
      education materials. Future system features desired by clinicians included an
      electronic, Web-based system with real-time, trended data, reasonable alerts, and
      tailored information for patients.

PMID- 28497472
TI  - Current knowledge on biomarkers for contact sensitization and allergic contact
      dermatitis.
AB  - Contact sensitization is common and affects up to 20% of the general population.
      The clinical manifestation of contact sensitization is allergic contact
      dermatitis. This is a clinical expression that is sometimes difficult to
      distinguish from other types of dermatitis, for example irritant and atopic
      dermatitis. Several studies have examined the pathogenesis and severity of
      allergic contact dermatitis by measuring the absence or presence of various
      biomarkers. In this review, we provide a non-systematic overview of biomarkers
      that have been studied in allergic contact dermatitis. These include genetic
      variations and mutations, inflammatory mediators, alarmins, proteases,
      immunoproteomics, lipids, natural moisturizing factors, tight junctions, and
      antimicrobial peptides. We conclude that, despite the enormous amount of data,
      convincing specific biomarkers for allergic contact dermatitis are yet to be
      described.

PMID- 28497473
TI  - Topical analgesics for acute and chronic pain in adults - an overview of Cochrane
      Reviews.
AB  - BACKGROUND: Topical analgesic drugs are used for a variety of painful conditions.
      Some are acute, typically strains or sprains, tendinopathy, or muscle aches.
      Others are chronic, typically osteoarthritis of hand or knee, or neuropathic
      pain. OBJECTIVES: To provide an overview of the analgesic efficacy and associated
      adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory
      drugs (NSAIDs), salicylate rubefacients, capsaicin, and lidocaine) applied to
      intact skin for the treatment of acute and chronic pain in adults. METHODS: We
      identified systematic reviews in acute and chronic pain published to February
      2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The
      primary outcome was at least 50% pain relief (participant-reported) at an
      appropriate duration. We extracted the number needed to treat for one additional
      beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or
      formulation, and the number needed to treat for one additional harmful outcome
      (NNH) for adverse events. We also extracted information on withdrawals due to
      lack of efficacy or adverse events, systemic and local adverse events, and
      serious adverse events. We required information from at least 200 participants,
      in at least two studies. We judged that there was potential for publication bias
      if the addition of four studies of typical size (400 participants) with zero
      effect increased NNT compared with placebo to 10 (minimal clinical utility). We
      extracted GRADE assessment in the original papers, and made our own GRADE
      assessment. MAIN RESULTS: Thirteen Cochrane Reviews (206 studies with around
      30,700 participants) assessed the efficacy and harms from a range of topical
      analgesics applied to intact skin in a number of acute and chronic painful
      conditions. Reviews were overseen by several Review Groups, and concentrated on
      evidence comparing topical analgesic with topical placebo; comparisons of topical
      and oral analgesics were rare.For at least 50% pain relief, we considered
      evidence was moderate or high quality for several therapies, based on the
      underlying quality of studies and susceptibility to publication bias.In acute
      musculoskeletal pain (strains and sprains) with assessment at about seven days,
      therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314
      participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72%
      ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)),
      piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4
      (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies,
      1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88%
      diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to
      4.2)).In chronic musculoskeletal pain (mainly hand and knee osteoarthritis)
      therapies were topical diclofenac preparations for less than six weeks (43%
      diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)),
      ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573
      participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6
      to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8
      (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had
      moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2
      studies, 571 participants, NNT 11 (6.1 to 62)).We judged evidence of efficacy for
      other therapies as low or very low quality. Limited evidence of efficacy,
      potentially subject to publication bias, existed for topical preparations of
      ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel
      other than Emulgel, indomethacin, and ketoprofen plaster in acute pain
      conditions, and for salicylate rubefacients for chronic pain conditions. Evidence
      for other interventions (other topical NSAIDs, topical salicylate in acute pain
      conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic
      pain, and herbal remedies for any condition) was very low quality and typically
      limited to single studies or comparisons with sparse data.We assessed the
      evidence on withdrawals as moderate or very low quality, because of small numbers
      of events. In chronic pain conditions lack of efficacy withdrawals were lower
      with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants,
      number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and
      topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21,
      very low-quality evidence). Adverse event withdrawals were higher with topical
      capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants,
      NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7
      studies, 735 participants, NNH 26, very low-quality evidence), and topical
      diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very
      low-quality evidence).In acute pain, systemic or local adverse event rates with
      topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42
      studies, 6740 participants, high quality evidence). In chronic pain local adverse
      events with topical capsaicin low concentration (63%) were higher than topical
      placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6),
      high quality evidence. Moderate-quality evidence indicated more local adverse
      events than placebo in chronic pain conditions with topical diclofenac (NNH 16)
      and local pain with topical capsaicin high-concentration (NNH 16). There was
      moderate-quality evidence of no additional local adverse events with topical
      ketoprofen over topical placebo in chronic pain. Serious adverse events were rare
      (very low-quality evidence).GRADE assessments of moderate or low quality in some
      of the reviews were considered by us to be very low because of small numbers of
      participants and events. AUTHORS' CONCLUSIONS: There is good evidence that some
      formulations of topical diclofenac and ketoprofen are useful in acute pain
      conditions such as sprains or strains, with low (good) NNT values. There is a
      strong message that the exact formulation used is critically important in acute
      conditions, and that might also apply to other pain conditions. In chronic
      musculoskeletal conditions with assessments over 6 to 12 weeks, topical
      diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis,
      as did topical high-concentration capsaicin in postherpetic neuralgia. Though
      NNTs were higher, this still indicates that a small proportion of people had good
      pain relief.Use of GRADE in Cochrane Reviews with small numbers of participants
      and events requires attention.

PMID- 28497474
TI  - Single and multiple sevoflurane exposures during pregnancy and offspring behavior
      in mice.
AB  - BACKGROUND: The second trimester is a period of neurogenesis and neuronal
      migration, which can be affected by exposure to anesthetics. Studies also suggest
      that multiple exposures may have a greater impact on neurodevelopment. AIM: We
      investigated whether in utero single or multiple exposures to anesthetics caused
      long-term behavior changes. METHODS: Pregnant mice were randomly divided into
      four groups on gestational day 14 (GD 14). Mice in the Control * 1 group were
      exposed to 100% oxygen for 150 min. Mice in the Sevo * 1 group were also exposed
      to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the
      first 120 min. Mice in the Control * 3 and Sevo * 3 group were identically
      treated as Control * 1 and Sevo * 1 group for three consecutive days,
      respectively (GD 14-16). Behavioral tests were performed only with the male
      offspring at the age of 2-4 months. Synaptic plasticity was also compared by
      inducing long-term potentiation in acute hippocampal slices. RESULTS: Single or
      multiple sevoflurane exposures in pregnant mice during the second trimester did
      not cause long-lasting behavioral consequences or changes in long-term synaptic
      plasticity of their offspring. CONCLUSION: Our study suggests that neither single
      nor multiple exposures of mice to sevoflurane during the fetal developmental
      period induces long-term behavioral dysfunctions or affects long-term synaptic
      plasticity. Additional studies focusing on early stages of neurodevelopment are
      necessary to confirm the effects of sevoflurane exposure during pregnancy.

PMID- 28497475
TI  - Quality of life of primary caregivers of children with cerebral palsy: a
      comparison between mother and grandmother caregivers in Anhui province of China.
AB  - BACKGROUND: The aims of the study are to evaluate the quality of life of mother
      and grandmother primary caregivers of children with cerebral palsy (CP) and to
      compare the difference between these two groups of caregivers. METHODS: We
      recruited 125 mother and 52 grandmother primary caregivers of children with CP.
      All the primary caregivers were interviewed with the short-form 36 (SF-36) health
      survey version 2.0 and with researcher-designed questionnaires for family
      background. As for the children, social-demographic characteristics, medical
      history and the result of a physical examination performed by a paediatric
      specialist in neurological rehabilitation were also collected. RESULTS: Mother
      and grandmother caregivers scored lower than their counterparts in the general
      population in both summary scores. Grandmother caregivers had lower scores than
      mother caregivers in all eight domains and in the two summary scores, with all
      differences being statistically significant (P < 0.05), except for the domain of
      the mental component summary score (P = 0.618). The differences were found
      particularly remarkable in the domains of physical functioning, role physical,
      bodily pain and also the physical component summary score (P < 0.001).
      CONCLUSIONS: The quality of life is significantly unsatisfactory in both mother
      and grandmother primary caregivers of children with CP; this research provides
      evidence for the need of the monitoring of these caregivers.

PMID- 28497476
TI  - Optimization of a novel large field of view distortion phantom for MR-only
      treatment planning.
AB  - PURPOSE: MR-only treatment planning requires images of high geometric fidelity,
      particularly for large fields of view (FOV). However, the availability of large
      FOV distortion phantoms with analysis software is currently limited. This work
      sought to optimize a modular distortion phantom to accommodate multiple bore
      configurations and implement distortion characterization in a widely
      implementable solution. METHOD AND MATERIALS: To determine candidate materials,
      1.0 T MR and CT images were acquired of twelve urethane foam samples of various
      densities and strengths. Samples were precision-machined to accommodate 6 mm
      diameter paintballs used as landmarks. Final material candidates were selected by
      balancing strength, machinability, weight, and cost. Bore sizes and minimum
      aperture width resulting from couch position were tabulated from the literature
      (14 systems, 5 vendors). Bore geometry and couch position were simulated using
      MATLAB to generate machine-specific models to optimize the phantom build.
      Previously developed software for distortion characterization was modified for
      several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously
      published 1.0 T results, and integrated into the 3D Slicer application platform.
      RESULTS: All foam samples provided sufficient MR image contrast with paintball
      landmarks. Urethane foam (compressive strength ~1000 psi, density ~20 lb/ft3 )
      was selected for its accurate machinability and weight characteristics. For
      smaller bores, a phantom version with the following parameters was used: 15 foam
      plates, 55 * 55 * 37.5 cm3 (L*W*H), 5,082 landmarks, and weight ~30 kg. To
      accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 * 55
      * 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization
      software was implemented as an external module into 3D Slicer's plugin framework
      and results agreed with the literature. CONCLUSION: The design and implementation
      of a modular, extendable distortion phantom was optimized for several bore
      configurations. The phantom and analysis software will be available for multi
      institutional collaborations and cross-validation trials to support MR-only
      planning.

PMID- 28497477
TI  - Fontan operation with bilateral conduits for the treatment of pulmonary
      arteriovenous fistulas in a patient with polysplenia after reconstruction of a
      non-confluent pulmonary artery.
AB  - We describe a case involving a successful Fontan procedure for the treatment of
      pulmonary arteriovenous fistulas in a patient with polysplenia. The patient was
      diagnosed with bilateral superior vena cavae, interrupted inferior vena cava with
      azygos connection, wide separate hepatic veins, and central pulmonary artery
      stenosis following repair of a non-confluent pulmonary artery. Bilateral
      extracardiac conduits were used to connect each hepatic vein to the pulmonary
      artery, opposite each superior vena cava. Clinical improvement in the pulmonary
      arteriovenous fistulas was observed within 4 months after surgery.

PMID- 28497478
TI  - Comparison of the clinical efficacy and safety of the on-demand use of
      paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in
      treatment of patients with premature ejaculation: A randomised placebo-controlled
      clinical trial.
AB  - The aim of the study was to compare the clinical efficacy and safety of the on
      demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with
      sildenafil in treatment of patients with premature ejaculation (PE). In a single
      blind placebo-controlled clinical study, 150 PE patients without erectile
      dysfunction (ED) were included during the period of March 2015 to May 2016.
      Patients were randomly divided into five groups (30 patients each). On demand
      placebo, paroxetine (30 mg), dapoxetine (30 mg), sildenafil citrate (50 mg) and
      combined dapoxetine (30 mg) with sildenafil citrate (50 mg) were given for
      patients for 6 weeks in each group respectively. All patients were instructed to
      record intravaginal ejaculatory latency time (IELT) and evaluated with Premature
      Ejaculation Diagnostic Tool (PEDT) and the patient satisfaction score before and
      after treatment. The mean of IELT, satisfaction score and PEDT in all groups was
      significantly improved after treatment (p value = .001). Combined dapoxetine with
      sildenafil group had the best values of IELT, satisfaction scores and PEDT in
      comparison with other treatment groups (p value <.001). The combined dapoxetine
      with sildenafil therapy could significantly improve PE patients without ED as
      compared to paroxetine alone or dapoxetine alone or sildenafil alone with
      tolerated adverse effects.

PMID- 28497479
TI  - Proximate composition, amino acid and fatty acid profiles of marine snail Rapana
      venosa meat, visceral mass and operculum.
AB  - BACKGROUND: Rapana venosa (Rv), an important marine snail, demonstrates an
      increasing nutritional and economic importance. However, there is still limited
      information available on their nutritional composition. The present study
      highlights and provides new information on the proximate composition, amino acid
      and fatty acid profiles of different body parts of Rv, aiming for its better
      application and research. RESULTS: The operculum contained a high amount of
      protein and flavor amino acids. The edible tissues, including meat and visceral
      mass, were valuable sources of essential amino acids (EAA) apart from methionine
      and cysteine. In addition, the meat contained high amount of taurine. Fatty acid
      analysis indicated that the edible tissues contained high amounts of omega3 fatty
      acids, especially eicosapentaenoic acid (EPA) (C20:5omega3) and docosahexaenoic
      acid (DHA) (C22:6omega3), and had a low omega6/omega3 fatty acid ratio.
      Interestingly, significantly higher concentrations of most nutritional elements
      such as fat, EAA, EPA and DHA, were found in the visceral mass compared to those
      in the meat. CONCLUSION: The operculum of Rv may became a very interesting source
      for some protein and flavor peptide development, and the edible parts of Rv may
      be utilized for special dietary applications requiring high amounts of taurine,
      EPA, DHA and a lower omega6/omega3 fatty acid ratio. (c) 2017 Society of Chemical
      Industry.

PMID- 28497480
TI  - Effectiveness of portable electronic and optical magnifiers for near vision
      activities in low vision: a randomised crossover trial.
AB  - PURPOSE: To compare the performance of near vision activities using additional
      portable electronic vision enhancement systems (p-EVES), to using optical
      magnifiers alone, by individuals with visual impairment. METHODS: A total of 100
      experienced optical aid users were recruited from low vision clinics at
      Manchester Royal Eye Hospital, Manchester, UK, to a prospective two-arm cross
      over randomised controlled trial. Reading, performance of near vision activities,
      and device usage were evaluated at baseline; and at the end of each study arm
      (Intervention A: existing optical aids plus p-EVES; Intervention B: optical aids
      only) which was after 2 and 4 months. RESULTS: A total of 82 participants
      completed the study. Overall, maximum reading speed for high contrast sentences
      was not statistically significantly different for optical aids and p-EVES,
      although the critical print size and threshold print size which could be accessed
      with p-EVES were statistically significantly smaller (p < 0.001 in both cases).
      The optical aids were used for a larger number of tasks (p < 0.001), and used
      more frequently (p < 0.001). However p-EVES were preferred for leisure reading by
      70% of participants, and allowed longer duration of reading (p < 0.001). During
      the study arm when they had a p-EVES device, participants were able to carry out
      more tasks independently (p < 0.001), and reported less difficulty with a range
      of near vision activities (p < 0.001). CONCLUSIONS: The study provides evidence
      that p-EVES devices can play a useful role in supplementing the range of low
      vision aids used to reduce activity limitation for near vision tasks.

PMID- 28497481
TI  - Harnessing polarisation transfer to indazole and imidazole through signal
      amplification by reversible exchange to improve their NMR detectability.
AB  - The signal amplification by reversible exchange (SABRE) approach has been used to
      hyperpolarise the substrates indazole and imidazole in the presence of the co
      ligand acetonitrile through the action of the precataysts [IrCl(COD)(IMes)] and
      [IrCl(COD)(SIMes)]. 2 H-labelled forms of these catalysts were also examined. Our
      comparison of the two precatalysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)],
      coupled with 2 H labelling of the N-heterocyclic carbene and associated
      relaxation and polarisation field variation studies, demonstrates the critical
      and collective role these parameters play in controlling the efficiency of signal
      amplification by reversible exchange. Ultimately, with imidazole, a 700-fold1 H
      signal gain per proton is produced at 400 MHz, whilst for indazole, a 90-fold
      increase per proton is achieved. The co-ligand acetonitrile proved to optimally
      exhibit a 190-fold signal gain per proton in these measurements, with the
      associated studies revealing the importance the substrate plays in controlling
      this value. Copyright (c) 2017 The Authors. Magnetic Resonance in Chemistry
      published by John Wiley & Sons Ltd.

PMID- 28497482
TI  - Quality changes and shelf-life extension of ready-to-eat fish patties by adding
      encapsulated citric acid.
AB  - BACKGROUND: Citric acid is commonly used as a flavoring and preservative in food
      and beverages. The effect of adding citric acid directly or encapsulated (each at
      1 and 2 g kg-1 ) on the quality and shelf-life of ready-to-eat sea bass patties
      was evaluated during storage at 4  degrees C in vacuum skin packaging. RESULTS:
      Microbial growth and total basic volatile nitrogen were maintained at relatively
      low levels up to 8 weeks of storage. With respect to oxidative stability, the
      addition of encapsulated citric acid minimized secondary oxidation values more
      efficiently than its direct addition, regardless of the concentration. This is in
      agreement with the decreased fishy odor observed in those patties containing
      encapsulated citric acid. Accordingly, sensory analysis showed that the addition
      of encapsulated citric acid at 1 g kg-1 resulted in lower scores in fish aroma
      compared to that of the control. Sourness is dependent on the amount of citric
      acid added, regardless of the form (direct or encapsulated). CONCLUSIONS: The
      form of citric acid addition, rather than the amount of citric acid added, caused
      changes in texture. Therefore, the use of encapsulated citric acid represents a
      suitable strategy that is of great interest in the seafood industry. (c) 2017
      Society of Chemical Industry.

PMID- 28497483
TI  - Incentives to patients versus incentives to health care providers: The users'
      perspective.
AB  - In theory, health care providers may adapt their professional behavior to the
      financial incentives resulting from their remuneration. Our research question is
      whether the users of health care services anticipate such behavior from their
      general practitioner (GP) and, if they do, what consequences such anticipation
      has on their preferences regarding financial incentives. Our theoretical model
      explains users' preferences for one or another incentives scheme, disentangling
      the financial motives (incentives amounts, wealth) from the behavioral ones
      (perceived GPs' sensitivity to incentives). We empirically test our theoretical
      predictions using data from a survey that elicits individual preferences for
      either patient or provider hypothetical incentives in France. The empirical
      results confirm the theoretical ones: users tend to prefer incentives to patients
      rather than to GPs when the amount of GP incentives is high, when the amount of
      patient incentives is low, when they anticipate that their GP's medical decisions
      are affected by financial incentives or when their wealth is high. Otherwise,
      they prefer their GP to face financial incentives.

PMID- 28497484
TI  - CD44 variant isoform 9 emerges in response to injury and contributes to the
      regeneration of the gastric epithelium.
AB  - The CD44 gene encodes several protein isoforms due to alternative splicing and
      post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is
      expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands
      during repair, CD44v9 may be play a funcitonal role during the process of
      regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a
      regenerative cell lineage responsive to infiltrating macrophages during
      regeneration of the gastric epithelium. Ulcers were induced in CD44-deficient
      (CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the
      serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived
      from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers,
      CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days
      post-injury. Human-derived gastric organoids were generated from stomach tissue
      collected from elderly (>55 years) or young (14-20 years) patients. Organoids
      were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of
      injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human
      derived immune cells (hnNRGS) and the immune profile anlayzed by CyTOF. CD44v9
      expression emerged within regenerating glands the ulcer margin in response to
      injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice
      exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted
      in CD44KO mice by transplanted CD55v9-expressing gastric organoids. NSG mice
      exhibited loss of CD44v9 expression and gastric repair. Transplantation of human
      derived gastric organoids from young, but not aged stomachs promoted repair in
      NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS
      animals exhibited reduced ulcer sizes, an infiltration of human CD162+
      macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of
      the gastic epithelium CD44v9 emerges within a regenerative cell lineage that
      coincides with macrophage inflitration within the injured mucosa. Copyright (c)
      2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 28497485
TI  - Creating chronicity.
AB  - An authentic sickness history is the vantage point for juxtaposing a biomedical
      and a biographical-phenomenological reading. What, in a biomedical framework,
      appears to be a longstanding state of comorbidity of different and unrelated
      types of diseases is rendered transparent in a biographical reading. This
      particular reading, evidencing the shortcomings of a biomedical framework
      regarding identifying the social sources of an increasingly complex burden of
      disease, is reflected upon in light of recent research in the neurosciences.
      Thus, the biomedical contribution to a sickness history is demonstrated, with its
      resultant multimorbidity, chronification, and complete incapacitation of a woman
      despite the continuing and nearly excessive involvement of the health care
      system.

PMID- 28497488
TI  - The common parasite Toxoplasma gondii induces prostatic inflammation and
      microglandular hyperplasia in a mouse model.
AB  - BACKGROUND: Inflammation is the most prevalent and widespread histological
      finding in the human prostate, and associates with the development and
      progression of benign prostatic hyperplasia and prostate cancer. Several factors
      have been hypothesized to cause inflammation, yet the role each may play in the
      etiology of prostatic inflammation remains unclear. This study examined the
      possibility that the common protozoan parasite Toxoplasma gondii induces
      prostatic inflammation and reactive hyperplasia in a mouse model. METHODS: Male
      mice were infected systemically with T. gondii parasites and prostatic
      inflammation was scored based on severity and focality of infiltrating leukocytes
      and epithelial hyperplasia. We characterized inflammatory cells with flow
      cytometry and the resulting epithelial proliferation with bromodeoxyuridine
      (BrdU) incorporation. RESULTS: We found that T. gondii infects the mouse prostate
      within the first 14 days of infection and can establish parasite cysts that
      persist for at least 60 days. T. gondii infection induces a substantial and
      chronic inflammatory reaction in the mouse prostate characterized by monocytic
      and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results
      in reactive hyperplasia, involving basal and luminal epithelial proliferation,
      and the exhibition of proliferative inflammatory microglandular hyperplasia in
      inflamed mouse prostates. CONCLUSIONS: This study identifies the common parasite
      T. gondii as a new trigger of prostatic inflammation, which we used to develop a
      novel mouse model of prostatic inflammation. This is the first report that T.
      gondii chronically encysts and induces chronic inflammation within the prostate
      of any species. Furthermore, T. gondii-induced prostatic inflammation persists
      and progresses without genetic manipulation in mice, offering a powerful new
      mouse model for the study of chronic prostatic inflammation and microglandular
      hyperplasia.

PMID- 28497486
TI  - 5D whole-heart sparse MRI.
AB  - PURPOSE: A 5D whole-heart sparse imaging framework is proposed for simultaneous
      assessment of myocardial function and high-resolution cardiac and respiratory
      motion-resolved whole-heart anatomy in a single continuous noncontrast MR scan.
      METHODS: A non-electrocardiograph (ECG)-triggered 3D golden-angle radial balanced
      steady-state free precession sequence was used for data acquisition. The acquired
      3D k-space data were sorted into a 5D dataset containing separated cardiac and
      respiratory dimensions using a self-extracted respiratory motion signal and a
      recorded ECG signal. Images were then reconstructed using XD-GRASP, a
      multidimensional compressed sensing technique exploiting correlations/sparsity
      along cardiac and respiratory dimensions. 5D whole-heart imaging was compared
      with respiratory motion-corrected 3D and 4D whole-heart imaging in nine
      volunteers for evaluation of the myocardium, great vessels, and coronary
      arteries. It was also compared with breath-held, ECG-gated 2D cardiac cine
      imaging for validation of cardiac function quantification. RESULTS: 5D whole
      heart images received systematic higher quality scores in the myocardium, great
      vessels and coronary arteries. Quantitative coronary sharpness and length were
      always better for the 5D images. Good agreement was obtained for quantification
      of cardiac function compared with 2D cine imaging. CONCLUSION: 5D whole-heart
      sparse imaging represents a robust and promising framework for simplified
      comprehensive cardiac MRI without the need for breath-hold and motion correction.
      Magn Reson Med 79:826-838, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 28497487
TI  - Systematic review with meta-analysis: the efficacy of vonoprazan-based triple
      therapy on Helicobacter pylori eradication.
AB  - BACKGROUND: In order to increase eradication rates, vonoprazan, a novel potassium
      competitive acid blocker, has been used in Helicobacter pylori eradication
      therapy. AIM: To summarise the results of the efficacy of vonoprazan-based triple
      therapy, helping clinicians to better understand the benefit of vonoprazan in the
      treatment of H. pylori infection. METHODS: We conducted a systematic literature
      search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords
      "vonoprazan," "takecab", "TAK-438," "potassium," "competitive," "potassium
      competitive," "Helicobacter," and "pylori." Studies were included if they
      evaluated the eradication rate between the vonoprazan-based and proton pump
      inhibitor (PPI)-based triple therapies. RESULTS: Ten studies and 10 644 patients
      were evaluated. The crude H. pylori eradication rate determined by intention-to
      treat analysis was 87.9% and 72.8% in the vonoprazan-based triple therapy and PPI
      based triple therapy respectively. The eradication rate of the vonoprazan-based
      triple therapy was superior to that of the PPI-based triple therapy (pooled risk
      ratio [RR] [95% confidence interval (CI)]=1.19 [1.15-1.24]) In addition, there
      was no significant difference in dropout rate due to adverse event between the
      regimens (pooled RR of the vonoprazan-based triple therapy [95% CI]=0.69 [0.23
      2.03]). The incidence of any adverse events also did not differ between the
      regimens (pooled RR [95% CI]=1.02 [0.78-1.34]). CONCLUSIONS: The vonoprazan-based
      triple therapy showed superior efficacy in terms of H. pylori eradication as
      compared to the PPI-based triple therapy. In addition, the vonoprazan-based
      triple therapy showed comparable tolerability and incidence of adverse events.

PMID- 28497489
TI  - Efficacy and safety of telaprevir with natural human interferon-beta and
      ribavirin in Japanese chronic hepatitis C patients with depression.
AB  - AIM: To assess the efficacy and safety of telaprevir (TVR) when used in
      combination with natural human interferon-beta (IFN-beta) and ribavirin (RBV) for
      genotype 1 patients with depression compared to IFN-beta/RBV therapy in Japan. We
      also examined the efficacy of the TVR/IFN-beta/RBV therapy in treatment failure
      genotype 2 patients with depression. METHODS: For the genotype 1 patients, 30
      patients received TVR (750 mg every 8 h) for 12 weeks combined with IFN-beta and
      RBV for 24 weeks (Group A), and 30 received IFN-beta and RBV for 48 weeks (Group
      B). For the genotype 2 patients, 14 patients were dosed only with the TVR-based
      regimen. RESULTS: The sustained virologic response (SVR) rates for Group A and
      Group B were 63.3% and 20.0%, respectively (P = 0.001, likelihood ratio test).
      The SVR rate for genotype 2 patients previously treated with pegylated IFN and/or
      RBV was 71.4%. No patient dropped out due to exacerbation of depression. The
      trend of platelet counts after the drugs were given was similar in the TVR/IFN
      beta/RBV therapy group and the IFN-beta/RBV therapy group. Common resistance
      associated variants of TVR were identified in 4 of the 13 patients who did not
      achieve SVR. CONCLUSION: This study showed that an addition of TVR to IFN
      beta/RBV therapy raised SVR in previously treated and untreated genotype 1
      patients and previously treated genotype 2 patients with chronic hepatitis C and
      depression.

PMID- 28497490
TI  - Application of monolithic chromatographic supports in virus research.
AB  - Key properties of monolithic chromatographic supports, make them suitable for
      separation and/or concentration of large biomolecules, especially virus particles
      and viral genomes. One by one, the studies that have been completed so far,
      contributed to the knowledge that monolith chromatography has hardly any
      limitation to be applied in virus research. Viruses of different sizes,
      possessing icosahedral structure and symmetrical morphology, as well as rod
      shaped or filamentous viruses with helical structure, even enveloped ones, all of
      them could be successfully managed by means of monolith chromatography. Same is
      true for viral genomes, primarily when being distinct from other nucleic acid
      forms present in a host cell. This review is exclusively focused on viruses. It
      describes the application of monolith chromatography to different problematics
      within the virus research field. The reviewed achievements offer new
      possibilities and trigger new aspects in virology.

PMID- 28497491
TI  - Male child with somatic mosaic Osteopathia Striata with Cranial Sclerosis caused
      by a novel pathogenic AMER1 frameshift mutation.
AB  - Osteopathia striata with cranial sclerosis (OSCS; OMIM #300373) is a rare X
      linked dominant condition caused by mutations in the AMER1 gene (also known as
      WTX or FAM123B). It is a condition which usually affects females in whom the
      clinical phenotype can be extremely variable. Conversely affected males typically
      die in utero or during the neonatal period [Perdu et al. (); Clinical Genetics
      80: 383-388; Vasiljevic et al. (); Prenatal Diagnosis 35: 302-304]. There have
      been a small number of reported cases of surviving males, including three
      patients who are somatic mosaic for the condition [Chenier, Noor, Dupuis,
      Stavropoulos, & Mendoza-Londono, (); American Journal of Medical Genetics Part A
      158A: 2946-2952; Holman et al. (); American Journal of Medical Genetics Part A
      155A: 2397-2408; Joseph, Shoji, & Econs, (); The Journal of Clinical
      Endocrinology and Metabolism 95: 1506-1507]. We report a case of a male child who
      has proven somatic mosaicism for OSCS associated with a novel pathogenic
      frameshift mutation, c.607_611delAGGCC (p.Arg203 fs) in AMER1. We describe the
      multisystemic clinical features which include macrocephaly with ventriculomegaly
      and requirement for ventriculoperitoneal shunt, cleft palate, and respiratory
      difficulties after birth requiring tracheostomy insertion, persistent patent
      ductus arteriosus, failure to thrive and gastrostomy insertion, growth
      retardation, ophthalmoplegia, kidney malformation, cryptorchidism, and
      developmental delay. The use of new technologies with next generation sequencing
      (NGS) may improve the detection rate of mosaicism in rare conditions.

PMID- 28497492
TI  - Dermatitis herpetiformis (Duhring's disease): a therapeutic challenge.

PMID- 28497493
TI  - Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM
      Inhibitors.
AB  - This study reports a novel class of inhibitors of uridine 5'-diphosphate (UDP)
      galactopyranose mutase (UGM) derived from a screening of natural products. This
      enzyme is an essential biocatalyst involved in the cell wall biosynthesis of
      Mycobacterium tuberculosis. Flavonoids are potent inhibitors of UGM. The
      synthesis of novel methylated flavonoids allowed a structure-activity
      relationship analysis to be performed and which functional groups and structural
      elements were required for UGM inhibition could be determined. The binding mode
      of one of the best inhibitors was found to be noncompetitive. Docking simulations
      indicated that this molecule was likely to bind UGM in its open conformation, in
      a cavity recently identified as a "druggable" pocket. Importantly, two of the
      best inhibitors of the M. tuberculosis UGM displayed moderate activity against
      whole M. tuberculosis cells. This study reports the first natural products that
      act as inhibitor of UGM. Given the importance of natural products in medicinal
      chemistry, these results create new opportunities for the discovery of new
      antitubercular agents.

PMID- 28497494
TI  - Global assays of fibrinolysis.
AB  - Fibrinolysis is an important and integral part of the hemostatic system. Acting
      as a balance to blood coagulation, the fibrinolytic system protects the body from
      unwanted thrombus formation and occlusion of blood vessels. As long as blood
      coagulation and fibrinolysis remain in equilibrium, response to injury, such as
      vessel damage, is appropriately regulated. However, alterations in this balance
      may lead to thrombosis or bleeding. A variety of methods have been proposed to
      assess fibrinolytic activity in blood or its components, but due to the
      complexity of the system, the design of a "gold standard" assay that reflects
      overall fibrinolysis has remained an elusive goal. In this review, we describe
      the most commonly used methods that have been described, such as
      thromboelastography (TEG and ROTEM), global fibrinolytic capacity in plasma and
      whole blood, plasma turbidity methods, simultaneous thrombin and plasmin
      generation assays, euglobulin clot lysis time and fibrin plate methods. All of
      these assays have strengths and limitations. We suggest that some methods may be
      preferable for detecting hypofibrinolytic conditions, whereas others may be
      better for detecting hyperfibrinolytic states.

PMID- 28497495
TI  - Tattooing and psoriasis: a case series and review of the literature.
AB  - BACKGROUND: Koebner phenomenon (KP) affects from a quarter to a third of the
      patients with psoriasis and can occur on tattoos MATERIAL AND METHODS: We
      retrospectively reviewed a case series of seven tattooed patients with an
      isomorphic response on their tattoos or partial psoriasis patches on their
      tattoos. We collected the demographic data, the past history of psoriasis, the
      clinical presentation, and the outcomes. We also performed a review of the
      literature. We tried to classify the different clinical profile of KP/psoriasis
      on tattoos accordingly. RESULTS: Six men and one woman with a median age of 36 +/
      6.4 years old were included. Five disclosed a KP in a recent tattoo within days
      to 1 month after its completion. Fifteen additional cases were collected from the
      literature (8 men, median age 22 +/- 8.2 years old). The delay of psoriasis flare
      up after tattooing was rather short, from a few weeks to several months. We found
      a high variability in the clinical presentation with five clinical
      subtypes/profiles of psoriasis on tattoos. A possible confusion between "genuine"
      KP on tattoos and the coincidental occurrence of psoriasis patches on tattoos is
      possible in some cases of the literature. Patients were mainly managed locally,
      rarely by systemic treatments or biologics. CONCLUSION: Koebner phenomenon on
      tattoos may occur in patients with psoriasis under various forms. The evolution
      is benign, and psoriasis is not a contraindication for tattooing, but patients
      need proper counseling before getting tattooed.

PMID- 28497496
TI  - Percutaneous left atrial decompression in adults with refractory cardiogenic
      shock supported with veno-arterial extracorporeal membrane oxygenation.
AB  - BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) distention, a recognized
      complication in patients supported with veno-arterial extracorporeal membrane
      oxygenation (VA-ECMO) for refractory cardiogenic shock, can lead to pulmonary
      edema, increased myocardial oxygen consumption, and LV thrombus formation. Atrial
      septostomy was examined as a management strategy for LV distension. METHODS: Of
      72 patients supported with VA-ECMO, seven patients underwent atrial septostomy
      through a trans-septal approach. The primary indication for atrial septostomy was
      refractory pulmonary edema. RESULTS: The mean time from ECMO initiation to LA
      decompression was 1.3 days (range 0-2 days). There was a 100% procedural success
      rate with improvement in pulmonary edema. Five patients survived to discharge
      with one patient exhibiting recovery of biventricular function, two patients were
      transplanted, one patient was decannulated, and one patient was transitioned to
      long-term durable ventricular assist device. Two patients died, one from multi
      organ failure and one with severe anoxic brain injury. CONCLUSION: Atrial
      septostomy is an effective method of LV decompression that can be performed
      safely with a high success rate.

PMID- 28497497
TI  - Simultaneous measurement of macro- and microvascular blood flow and oxygen
      saturation for quantification of muscle oxygen consumption.
AB  - PURPOSE: To investigate the relationship between blood flow and oxygen
      consumption in skeletal muscle, a technique called "Velocity and Perfusion,
      Intravascular Venous Oxygen saturation and T2*" (vPIVOT) is presented. vPIVOT
      allows the quantification of feeding artery blood flow velocity, perfusion,
      draining vein oxygen saturation, and muscle T2*, all at 4-s temporal resolution.
      Together, the measurement of blood flow and oxygen extraction can yield muscle
      oxygen consumption ( VO2) via the Fick principle. METHODS: In five subjects,
      vPIVOT-derived results were compared with those obtained from stand-alone
      sequences during separate ischemia-reperfusion paradigms to investigate the
      presence of measurement bias. Subsequently, in 10 subjects, vPIVOT was applied to
      assess muscle hemodynamics and VO2 following a bout of dynamic plantar flexion
      contractions. RESULTS: From the ischemia-reperfusion paradigm, no significant
      differences were observed between data from vPIVOT and comparison sequences.
      After exercise, the macrovascular flow response reached a maximum 8 +/- 3 s after
      relaxation; however, perfusion in the gastrocnemius muscle continued to rise for
      101 +/- 53 s. Peak VO2 calculated based on mass-normalized arterial blood flow or
      perfusion was 15.2 +/- 6.7 mL O2 /min/100 g or 6.0 +/- 1.9 mL O2 /min/100 g,
      respectively. CONCLUSIONS: vPIVOT is a new method to measure blood flow and
      oxygen saturation, and therefore to quantify muscle oxygen consumption. Magn
      Reson Med 79:846-855, 2018. (c) 2017 International Society for Magnetic Resonance
      in Medicine.

PMID- 28497498
TI  - Cryoprotection and banking of living cells in a 3D multiple emulsion-based
      carrier.
AB  - The ability to preserve stem cells/cells with minimal damage for short and long
      periods of time is essential for advancements in biomedical therapies and
      biotechnology. New methods of cell banking are continuously needed to provide
      effective damage prevention to cells. This paper puts forward a solution to the
      problem of the low viability of cells during cryopreservation in a traditional
      suspension and storage by developing innovative multiple emulsion-based carriers
      for the encapsulation and cryopreservation of cells. During freezing-thawing
      processes, irreversible damage to cells occurs as a result of the formation of
      ice crystals, cell dehydration, and the toxicity of cryoprotectant. The proposed
      method was effective due to the "flexible" protective structure of multiple
      emulsions, which was proven by a high cell survival rate, above 90%. Results make
      new contributions in the fields of cell engineering and biotechnology and
      contribute to the development of methods for banking biological material.

PMID- 28497500
TI  - Adverse effects of leptin on histone-to-protamine transition during
      spermatogenesis are prevented by melatonin in Sprague-Dawley rats.
AB  - This study examines the effect of melatonin on leptin-induced changes in
      transition of histone to protamine in adult rats during spermatogenesis. Twelve
      week-old Sprague-Dawley rats were randomised into control, leptin-, leptin
      melatonin-10-, leptin-melatonin-20- and melatonin-10-treated groups with six rats
      per group. Leptin was given via intraperitoneal injections (i.p.) daily for 42
      days (60 MUg/kg body weight). Rats in the leptin- and melatonin-treated groups
      were given either 10 or 20 mg day-1  kg-1 body weight of leptin in drinking
      water. Melatonin-10-treated group received only 10 mg of melatonin day-1  kg-1
      body weight in drinking water for 42 days. Control rats received 0.1 ml of 0.9%
      saline. Upon completion of the treatment, sperm count, morphology and histone-to
      protamine ratio were estimated. Gene expression of HAT, HDAC1, HDAC2, H2B, H2A,
      H1, PRM1, PRM2, TNP1 and TNP2 was determined. Data were analysed using ANOVA.
      Sperm count was significantly lower, whereas the fraction of spermatozoa with
      abnormal morphology, the ratio of histone-to-protamine transition and the
      expressions of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1 were significantly higher in
      leptin-treated rats than those in controls or melatonin-treated rats. It appears
      that exogenous leptin administration adversely affects histone-to-protamine
      transition, which is prevented by concurrent administration of melatonin.

PMID- 28497499
TI  - Applying characteristic fragment filtering for rapid detection and identification
      of ingredients in rhubarb by HPLC coupled with linear ion trap-Orbitrap mass
      spectrometry.
AB  - Chemical characteristic fragment filtering in MSn chromatograms was proposed to
      detect and identify the components in rhubarb rapidly using high-performance
      liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry.
      Characteristic fragments consist of diagnostic ions and neutral loss fragments.
      Characteristic fragment filtering is a postacquisition data mining method for the
      targeted screening of groups with specific structures, including three steps:
      first, in order to comprehensively summarize characteristic fragments for global
      identification of the ingredients in rhubarb, representative authentic standards
      of dominant chemical categories contained in rhubarb were chosen, from which
      fragmentation rules and a characteristic fragments schedule were proposed;
      second, characteristic fragment filtering was used to rapidly recognize analogous
      skeletons; finally, combined with retention time, accurate mass, characteristic
      fragments, and previous literature, the structures of the filtered compounds were
      identified or tentatively characterized. As a result, a total of 271 compounds
      were detected and identified in rhubarb, including 34 anthraquinones, 83
      anthrones, 46 tannins, 17 stilbenes, 24 phenylbutanones, 26 acylglucosides, 26
      chromones, and 15 other compounds, 69 of which are potentially new compounds. The
      proposed characteristic fragment filtering strategy would be a reference for the
      large-scale detection and identification of the ingredients of herbal medicines.

PMID- 28497501
TI  - Assessing the role of Hartree-Fock exchange, correlation energy and long range
      corrections in evaluating ionization potential, and electron affinity in density
      functional theory.
AB  - Accurate determination of ionization potentials (IPs), electron affinities (EAs),
      fundamental gaps (FGs), and HOMO, LUMO energy levels of organic molecules play an
      important role in modeling and predicting the efficiencies of organic
      photovoltaics, OLEDs etc. In this work, we investigate the effects of Hartree
      Fock (HF) Exchange, correlation energy, and long range corrections in predicting
      IP and EA in Hybrid Functionals. We observe increase in percentage of HF exchange
      results in increase of IPs and decrease in EAs. Contrary to the general
      expectations inclusion of both HF exchange and correlation energy (from the
      second order perturbation theory MP2) leads to poor prediction. Range separated
      Hybrid Functionals are found to be more reliable among various DFT Functionals
      investigated. DFT Functionals predict accurate IPs whereas post HF methods
      predict accurate EAs. (c) 2017 Wiley Periodicals, Inc.

PMID- 28497502
TI  - Improving outcome of fungal diseases - Guiding experts and patients towards
      excellence.
AB  - Invasive fungal infections are on the rise and during recent years understanding
      the epidemiology of fungal infections improved. Over 1 billion people are
      affected and 25 million patients are at imminent risk of severe organ damage or
      death due to fungal infection. The European Confederation of Medical Mycology
      (ECMM), founded in 1993, is the roof organisation of 23 National Medical Mycology
      Societies in Europe. ECMM fights fungal infections at various levels, by creating
      and distributing scientific knowledge and promoting scientific exchange. In
      response to the increasing prevalence and management complexity of invasive
      fungal infections, ECMM recently launched three additional initiatives
      (https://www.ecmm.info/). (i) ECMM together with other European infectious
      diseases societies created a comprehensive set of European guidelines for the
      diagnostic and therapeutic management of invasive fungal infections. (ii) ECMM
      founded the ECMM Academy awarding fellow status (FECMM) to outstanding
      researchers who advanced medical mycology. The academy aims at strengthening
      networking activities between these researchers. (iii) Centres throughout the
      world can apply for ECMM Excellence Center Status. Following such application on
      site auditing of up to three levels of mycological work (clinical,
      microbiological, epidemiological/clinical trials) evaluates the excellence of a
      centre along predefined criteria. All three initiatives share a common ambition;
      they aim at improving outcome of fungal diseases through guiding experts and
      patients towards excellence. Acknowledging fungal infections as a global problem,
      all three initiatives explicitly reach out beyond European borders.

PMID- 28497503
TI  - Establishing Australian school re-entry service guidelines for children diagnosed
      with cancer.

PMID- 28497504
TI  - Semiconducting Coordination Polymers Based on the Predesigned Ternary Te-Fe-Cu
      Carbonyl Cluster and Conjugation-Interrupted Dipyridyl Linkers.
AB  - A series of semiconducting cluster-incorporated Cu-based coordination polymers,
      namely, 1D zigzag polymers [{TeFe3 (CO)9 Cu2 }(L)]n (L=1,2-bis(4-pyridyl)ethane
      (bpea), 1; L=1,2-bis(4-pyridyl)ethylene (bpee), 5), 2D honeycomb-like polymers
      [{TeFe3 (CO)9 Cu}Cu(L)2.5 ]n (L=bpea, 2; L=bpee, 6), and 2D wave-like cation
      anion polymer [{Cu2 (L)4 }({TeFe3 (CO)9 Cu}2 (L))]n (L=1,3-bis(4-pyridyl)propane
      (bpp), 4), as well as the macrocycle [{TeFe3 (CO)9 Cu2 }2 (bpp)2 ] (3) have been
      quantitatively synthesized via the liquid-assisted grinding from the pre-designed
      cluster [TeFe3 (CO)9 Cu2 (MeCN)2 ] with conjugated or conjugation-interrupted
      dipyridyl linkers. Notably, the most conjugation-interrupted bpp-bridged polymer
      4 exhibited extraordinary semiconducting characteristics with an ultra-narrow
      bandgap of 1.43 eV and a DC conductivity of 1.5*10-2 Omega-1  cm-1 , which
      violates our knowledge, mainly attributed to the through-space electron transport
      via non-classical C-H???O(carbonyl) hydrogen bonds and aromatic C-H???pi
      interactions. The incorporated Te-Fe-CO anions can not only provide numerous
      possibilities for secondary interactions within these Cu-based polymers but also
      serve as a redox-active coordination ligand to promote their conductivities. The
      intriguing structure-property relationships were studied by X-ray and DFT
      analyses and further demonstrated by significant change in the oxidation state of
      Cu atoms by XPS and Cu K-edge XANES.

PMID- 28497505
TI  - Resurgence of rabies in Hungary during 2013-2014: An attempt to track the origin
      of identified strains.
AB  - In 2013-2014, accumulation of rabies episodes raised concerns regarding ongoing
      elimination programme in Hungary. Nearly four dozen cases were identified over a
      13-month period in the central region of the country far behind the immunization
      zones. Although the outbreak was successfully controlled, the origin of disease
      remained unknown. In this study, we sequenced the partial N and G genes from 47
      Hungarian rabies virus (RV) strains isolated from the 2013-2014 outbreak.
      Sequencing and phylogenetic analysis of the N and G genes showed that the
      Hungarian RV isolates share high nucleotide similarity among each other (up to
      100%). When analysing the N gene, comparable sequence similarity was seen between
      the outbreak strains and some historic Romanian RV strains. Unfortunately, in the
      lack of available sequence data from the Romanian RV strains, the genetic
      relationship within the G gene could not be determined. Phylogenetic analysis of
      Hungarian RV isolates detected in the past revealed that multiple independent RV
      lineages circulated in our country over the past 25 years. The parental strain of
      the 2013-2014 outbreak may have been imported independently perhaps from east
      through transborder movement of a reservoir animal. Next to the introduction,
      this imported RV strain seems to have spread clonally in the affected area. Our
      findings indicate that despite effective control measures that, overall,
      minimized the incidence of rabies over the past decade, field and laboratory
      monitoring needs to be continued to make rabies elimination programme in Hungary
      successful.

PMID- 28497506
TI  - Left ventricular obstruction caused by a large hiatal hernia.
AB  - A 76-year-old man was admitted to our emergency department owing to chest pain,
      which started immediately after lunch. Although electrocardiogram revealed ST
      segment elevation with hyperacute T-wave changes in the anterior lead tracings,
      emergency coronary angiography revealed normal coronary arteries.
      Echocardiography revealed left ventricular (LV) compression with left ventricular
      obstruction (LVO) caused by an echogenic mass. Computed tomography clearly
      revealed compression of both left atrial (LA) and LV by a large hiatal hernia. A
      large hiatal hernia can induce cardiac symptoms resulting from cardiac
      compression. This case highlights a possible association between chest pain and
      LVO caused by a hiatal hernia.

PMID- 28497507
TI  - Ferrocene- and Biferrocene-Containing Macrocycles towards Single-Molecule
      Electronics.
AB  - Cyclic multiredox centered systems are currently of great interest, with new
      compounds being reported and developments made in understanding their behavior.
      Efficient, elegant, and high-yielding (for macrocyclic species) synthetic routes
      to two novel alkynyl-conjugated multiple ferrocene- and biferrocene-containing
      cyclic compounds are presented. The electronic interactions between the
      individual ferrocene units have been investigated through electrochemistry,
      spectroelectrochemistry, density functional theory (DFT), and crystallography to
      understand the effect of cyclization on the electronic properties and structure.

PMID- 28497508
TI  - New horizons for mental health research in intellectual disabilities.

PMID- 28497509
TI  - Characteristics and prognosis of glomangiopericytomas: A systematic review.
AB  - BACKGROUND: Glomangiopericytoma belongs to the category of borderline/low
      malignant-potential tumors of the sinonasal tract, but no studies about prognosis
      have been reported. METHODS: To define the characteristics of glomangiopericytoma
      and to identify its prognostic factors, a systematic review was performed. A
      total of 337 cases of glomangiopericytomas were analyzed. RESULTS: Patients with
      glomangiopericytoma demonstrating resection margin involvement and receiving
      radiotherapy/chemotherapy had a significantly worse disease-free survival time (P
      =  .014 and .006, respectively). Patients with glomangiopericytoma had a tendency
      toward longer overall survival when they were diagnosed at a younger age (<=60
      years; P = .001), did not demonstrate marginal involvement (P = .032),
      recurrence/metastasis (P = .002), or radiotherapy/chemotherapy (P = .010), and
      had a right-sided tumor (P < .001), actin-immunopositivity (P < .001), and CD34
      /BCL2-immunonegativities (P = .002 and .019, respectively). By multivariate
      analysis, actin (P < .001) and CD34 (P = .002) immunostaining were significantly
      related to the overall survival of patients with glomangiopericytoma. CONCLUSION:
      Actin and CD34 immunostaining could be used as independent prognostic indicators
      of glomangiopericytomas.

PMID- 28497510
TI  - The effect of health care expenditure on patient outcomes: Evidence from English
      neonatal care.
AB  - The relationship between health care expenditure and health outcomes has been the
      subject of recent academic inquiry in order to inform cost-effectiveness
      thresholds for health technology assessment agencies. Previous studies in public
      health systems have relied upon data aggregated at the national or regional
      level; however, there remains debate about whether the supply side effect of
      changes to expenditure are identifiable using data at this level of aggregation.
      We use detailed patient data derived from electronic neonatal records across
      England along with routinely available cost data to estimate the effect of
      changes to patient expenditure on clinical health outcomes in a well-defined
      patient population. A panel of 32 neonatal intensive care units for the period
      2009-2013 was constructed. Accounting for the potential endogeneity of
      expenditure a L100 increase in the cost per intensive care cot day (sample
      average cost: L1,127) is estimated to reduce the risk of mortality of 0.38
      percentage points (sample average mortality: 11.0%) in neonatal intensive care.
      This translates into a cost per life saved in neonatal intensive care of
      approximately L420,000.

PMID- 28497511
TI  - Effects of medical trainees' weight-loss history on perceptions of patients with
      obesity.
AB  - CONTEXT: Medical professionals often express weight-biased attitudes. Prior
      research suggests that people who overcome a challenge are critical of
      individuals who struggle to overcome the same challenge. Thus, medical trainees
      who have successfully achieved and maintained weight loss may express greater
      weight bias and more critical attitudes toward patients with obesity who fail to
      overcome these challenges. OBJECTIVES: This study was designed to determine the
      effects of medical trainees' weight-loss history on weight-biased attitudes and
      responses to patients with varying weight-loss outcomes. METHODS: An online
      survey was completed by 219 medical students and internal medicine residents.
      Participants' weight-biased attitudes were assessed before they were randomly
      assigned to read one of three patient vignettes in which the patient lost no
      weight, lost/regained weight, or lost/maintained weight. Independent measures
      included trainee gender, trainee weight loss and maintenance, and the three
      experimental conditions of patient outcomes. Dependent measures included the Anti
      Fat Attitudes (AFA) Questionnaire's Willpower and Dislike subscales, ratings (on
      a scale of 1-7) of compassion, frustration, and blame toward the patients
      presented in the vignettes, and perceptions of the physician-patient alliance.
      All analyses controlled for trainee body mass index. RESULTS: Among trainees,
      67.1% reported having successfully lost weight. Of those who had lost weight,
      79.5% reported maintaining their weight loss. Trainees who had successfully
      lost/maintained weight expressed less compassion toward patients across vignettes
      (5.4 +/- 1.2 versus 5.9 +/- 1.2; p<0.05), and more blame toward the patient who
      lost/regained weight than did trainees who had lost/regained weight (3.4 +/- 1.3
      versus 2.3 +/- 1.3; p<0.01). Overall, the patient who did not lose weight was
      viewed most negatively, followed by the patient who lost/regained (all p-values <
      0.05). Female (but not male) trainees who had successfully lost weight expressed
      stronger weight-biased attitudes on the AFA scales than did those who had never
      lost weight (all p-values < 0.01). CONCLUSIONS: Medical trainees' personal
      success with weight loss and maintenance may negatively affect their perceptions
      of patients with obesity who struggle with weight management.

PMID- 28497512
TI  - Children's intuitive sense of number develops independently of their perception
      of area, density, length, and time.
AB  - Young children can quickly and intuitively represent the number of objects in a
      visual scene through the Approximate Number System (ANS). The precision of the
      ANS - indexed as the most difficult ratio of two numbers that children can
      reliably discriminate - is well known to improve with development: whereas
      infants require relatively large ratios to discriminate number, children can
      discriminate finer and finer changes in number between toddlerhood and early
      adulthood. Which factors drive the developmental improvements in ANS precision?
      Here, we investigate the influence of four non-numeric dimensions - area,
      density, line length, and time - on ANS development, exploring the degree to
      which the ANS develops independently from these other dimensions, from inhibitory
      control, and from domain-general factors such as attention and working memory
      that are shared between these tasks. A sample of 185 children between the ages of
      2 and 12 years completed five discrimination tasks: approximate number, area,
      density, length, and time. We report three main findings. First, logistic growth
      models applied to both accuracy and Weber fractions (w; an index of ANS
      precision) across age reveal distinct developmental trajectories across the five
      dimensions: while area and length develop by adolescence, time and density do not
      develop fully until early adulthood, with ANS precision developing at an
      intermediate rate. Second, we find that ANS precision develops independently of
      the other four dimensions, which in turn develop independently of the ANS. Third,
      we find that ANS precision also develops independently from individual
      differences in inhibitory control (indexed as the difference in accuracy and w
      between Congruent and Incongruent ANS trials). Together, these results are the
      first to provide evidence for domain-specific improvements in ANS precision, and
      place children's maturing perception of number, space, and time into a broader
      developmental context.

PMID- 28497513
TI  - Supporting new (and not so new) health professionals.

PMID- 28497514
TI  - Running a successful trainee conference.

PMID- 28497515
TI  - Reflecting on simulation.

PMID- 28497516
TI  - Learning with and from peers.

PMID- 28497517
TI  - Reflecting on medical student surgical conferences.

PMID- 28497518
TI  - An innovative programme for premedical students.

PMID- 28497519
TI  - Living with advanced cancer and the role of the primary care provider: The
      missing piece in the survivorship discourse.
AB  - The period of survivorship has been identified as a distinct phase of the cancer
      continuum, and the key role of primary care providers in caring for cancer
      survivors has been recognized. However, much of the focus to date has been placed
      on cancer survivors who are treated with curative intent and survive cancer-free.
      Receiving less attention are those who are living with advanced, non-curative
      cancer. In this commentary, we review the current evidence about the
      characteristics of these survivors, their unmet needs and receipt of health care.
      We offer insights into future research, education and policy initiatives aiming
      to enhance the care for this population.

PMID- 28497520
TI  - Nitrous oxide for procedural analgesia at home in a child with epidermolysis
      bullosa.
AB  - Epidermolysis bullosa comprises a range of conditions characterized by fragile
      skin with painful blistering induced by minor trauma and friction. The Dowling
      Meara variant is a severe form characterized by disseminated painful blistering
      requiring lifelong skin and wound care. The natural history of the disease is
      characterized by a chronic course that tends to improve with advancing age.
      Various multimodal analgesic strategies have been proposed for painful procedures
      in children with epidermolysis bullosa. In this case report, we describe the use
      of nitrous oxide for pain control at home of blister treatments in a 4-year-old
      child with the Dowling-Meara variant.

PMID- 28497521
TI  - Erratum: "A new method to retrieve phase information for equiangular fan beam
      differential phase contrast computed tomography" [Med. Phys. 40, 031911(8pp.)
      (2013)].

PMID- 28497522
TI  - Erratum: "Experimental demonstration of passive acoustic imaging in the human
      skull cavity using CT-based aberration corrections" [Med. Phys. 42, 4385-4400
      (2015)].

PMID- 28497523
TI  - High MELD score does not adversely affect outcome of living donor liver
      transplantation: Experience in 1000 recipients.
AB  - In countries where deceased organ donation is scarce, there is a big gap between
      demand and supply of organs and living donor liver transplantation (LDLT) plays
      an important role in meeting this unmet need. This study was conducted to analyze
      the effect of pretransplant Model for End-stage Liver Disease (MELD) score on
      outcomes following LDLT. The outcome of 1000 patients who underwent LDLT from
      July 2010 to March 2015 was analyzed retrospectively. Patients were grouped into
      low MELD<25 and high MELD >=25 score to compare short-term outcomes. Cumulative
      overall survival rates were calculated using Kaplan-Meier methods. A total of 849
      recipients were in low MELD group (Mean MELD=16.90+/-9.2) and 151 were in high
      MELD group (Mean MELD=28.77+/-7.2). No significant difference in etiology of CLD
      was observed between groups except for a higher prevalence of hepatitis C virus
      (29.6% vs 19.9%, P=.01) in low MELD patients. No significant difference was
      observed in 1-year survival (88.5% vs 84.1%, P=.12) between the groups. The
      multivariate analysis showed that pretransplant MELD score does not predict
      survival of recipients. Pretransplant high MELD score does not adversely affect
      outcomes after LDLT. In view of shortage of deceased organs, LDLT can be a good
      option in high MELD recipients.

PMID- 28497524
TI  - Changing minds: Children's inferences about third party belief revision.
AB  - By the age of 5, children explicitly represent that agents can have both true and
      false beliefs based on epistemic access to information (e.g., Wellman, Cross, &
      Watson, 2001). Children also begin to understand that agents can view identical
      evidence and draw different inferences from it (e.g., Carpendale & Chandler,
      1996). However, much less is known about when, and under what conditions,
      children expect other agents to change their minds. Here, inspired by formal
      ideal observer models of learning, we investigate children's expectations of the
      dynamics that underlie third parties' belief revision. We introduce an agent who
      has prior beliefs about the location of a population of toys and then observes
      evidence that, from an ideal observer perspective, either does, or does not
      justify revising those beliefs. We show that children's inferences on behalf of
      third parties are consistent with the ideal observer perspective, but not with a
      number of alternative possibilities, including that children expect other agents
      to be influenced only by their prior beliefs, only by the sampling process, or
      only by the observed data. Rather, children integrate all three factors in
      determining how and when agents will update their beliefs from evidence.

PMID- 28497526
TI  - Prevention, removal and inactivation of Escherichia coli and Staphylococcus
      aureus biofilms using selected monoterpenes of essential oils.
AB  - AIMS: The aim of this study was to investigate the antibiofilm potential of five
      essential oils (EOs) components with cyclic (sabinene-SAB, carveol-C1, carvone
      C2) and acyclic (citronellol-C3 and citronellal-C4) structures against
      Escherichia coli and Staphylococcus aureus. METHODS AND RESULTS: The selected EOs
      components prevented biofilm set-up, with C3 and C4 causing remarkable effects.
      When applied against pre-established biofilms, they promoted high biomass removal
      and inactivation of biofilm cells. Moreover, no viable E. coli biofilm cells were
      detected after exposure to SAB at 5*MIC and 10*MIC and significant viability
      decrease was observed for both bacteria with the other EOs components. SAB, C3
      and C4 caused the most prominent effects apparently due to their octanol-water
      partition coefficient (Po/w), the number of rotatable bonds (n-ROTB) and the free
      hydroxyl groups. CONCLUSIONS: The overall results demonstrated that the selected
      EOs components, particularly SAB, C3 and C4 are of interest as new lead molecules
      to both prevent biofilm set-up and to control pre-established biofilms of E. coli
      and S. aureus. This article is protected by copyright. All rights reserved.

PMID- 28497527
TI  - Uncommon cause of pulmonary hypertension.

PMID- 28497525
TI  - Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors.
AB  - New federal regulations allow HIV-positive individuals to be live kidney donors;
      however, potential candidacy for donation is poorly understood given the
      increased risk of end-stage renal disease (ESRD) associated with HIV infection.
      To better understand this risk, we compared the incidence of ESRD among 41 968
      HIV-positive participants of North America AIDS Cohort Collaboration on Research
      and Design followed for a median of 5 years with the incidence of ESRD among
      comparable HIV-negative participants of National Health and Nutrition Examination
      III followed for a median of 14 years. We used risk associations from
      multivariable Cox proportional hazards regression to derive cumulative incidence
      estimates for selected HIV-positive scenarios (no history of diabetes,
      hypertension, AIDS, or hepatitis C virus coinfection) and compared these
      estimates with those from similarly selected HIV-negative scenarios. For 40-year
      old HIV-positive individuals with health characteristics that were similar to
      those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count
      >=500 cells/MUL, the 9-year cumulative incidence of ESRD was higher than that of
      their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white
      women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000
      among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive
      individuals with no comorbidities and well-controlled disease may be considered
      low-risk kidney donor candidates.

PMID- 28497528
TI  - Frequency-Swept Integrated Solid Effect.
AB  - The efficiency of continuous wave dynamic nuclear polarization (DNP) experiments
      decreases at the high magnetic fields used in contemporary high-resolution NMR
      applications. To recover the expected signal enhancements from DNP, we explored
      time domain experiments such as NOVEL which matches the electron Rabi frequency
      to the nuclear Larmor frequency to mediate polarization transfer. However,
      satisfying this matching condition at high frequencies is technically demanding.
      As an alternative we report here frequency-swept integrated solid effect (FS-ISE)
      experiments that allow low power sweeps of the exciting microwave frequencies to
      constructively integrate the negative and positive polarizations of the solid
      effect, thereby producing a polarization efficiency comparable to (+/-10 %
      difference) NOVEL. Finally, the microwave frequency modulation results in field
      profiles that exhibit new features that we coin the "stretched" solid effect.

PMID- 28497529
TI  - AAPM medical physics practice guideline 6.a.: Performance characteristics of
      radiation dose index monitoring systems.
AB  - The American Association of Physicists in Medicine (AAPM) is a nonprofit
      professional society whose primary purposes are to advance the science, education
      and professional practice of medical physics. The AAPM has more than 8,000
      members and is the principal organization of medical physicists in the United
      States. The AAPM will periodically define new practice guidelines for medical
      physics practice to help advance the science of medical physics and to improve
      the quality of service to patients throughout the United States. Existing medical
      physics practice guidelines will be reviewed for the purpose of revision or
      renewal, as appropriate, on their fifth anniversary or sooner. Each medical
      physics practice guideline represents a policy statement by the AAPM, has
      undergone a thorough consensus process in which it has been subjected to
      extensive review, and requires the approval of the Professional Council. The
      medical physics practice guidelines recognize that the safe and effective use of
      diagnostic and therapeutic radiology requires specific training, skills, and
      techniques, as described in each document. Reproduction or modification of the
      published practice guidelines and technical standards by those entities not
      providing these services is not authorized. The following terms are used in the
      AAPM practice guidelines: *Must and Must Not: Used to indicate that adherence to
      the recommendation is considered necessary to conform to this practice guideline.
      *Should and Should Not: Used to indicate a prudent practice to which exceptions
      may occasionally be made in appropriate circumstances.

PMID- 28497530
TI  - Short-term Memory in Childhood Dyslexia: Deficient Serial Order in Multiple
      Modalities.
AB  - In children with dyslexia, deficits in working memory have not been well
      specified. We assessed second-grade children with dyslexia, with and without
      concomitant specific language impairment, and children with typical development.
      Immediate serial recall of lists of phonological (non-word), lexical (digit),
      spatial (location) and visual (shape) items were included. For the latter three
      modalities, we used not only standard span but also running span tasks, in which
      the list length was unpredictable to limit mnemonic strategies. Non-word
      repetition tests indicated a phonological memory deficit in children with
      dyslexia alone compared with those with typical development, but this difference
      vanished when these groups were matched for non-verbal intelligence and language.
      Theoretically important deficits in serial order memory in dyslexic children,
      however, persisted relative to matched typically developing children. The
      deficits were in recall of (1) spoken digits in both standard and running span
      tasks and (2) spatial locations, in running span only. Children with dyslexia
      with versus without language impairment, when matched on non-verbal intelligence,
      had comparable serial order memory, but differed in phonology. Because serial
      orderings of verbal and spatial elements occur in reading, the careful
      examination of order memory may allow a deeper understanding of dyslexia and its
      relation to language impairment. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28497531
TI  - Exposure enriched outcome dependent designs for longitudinal studies of gene
      environment interaction.
AB  - Joint effects of genetic and environmental factors have been increasingly
      recognized in the development of many complex human diseases. Despite the
      popularity of case-control and case-only designs, longitudinal cohort studies
      that can capture time-varying outcome and exposure information have long been
      recommended for gene-environment (G * E) interactions. To date, literature on
      sampling designs for longitudinal studies of G * E interaction is quite limited.
      We therefore consider designs that can prioritize a subsample of the existing
      cohort for retrospective genotyping on the basis of currently available outcome,
      exposure, and covariate data. In this work, we propose stratified sampling based
      on summaries of individual exposures and outcome trajectories and develop a full
      conditional likelihood approach for estimation that adjusts for the biased
      sample. We compare the performance of our proposed design and analysis with
      combinations of different sampling designs and estimation approaches via
      simulation. We observe that the full conditional likelihood provides improved
      estimates for the G * E interaction and joint exposure effects over uncorrected
      complete-case analysis, and the exposure enriched outcome trajectory dependent
      design outperforms other designs in terms of estimation efficiency and power for
      detection of the G * E interaction. We also illustrate our design and analysis
      using data from the Normative Aging Study, an ongoing longitudinal cohort study
      initiated by the Veterans Administration in 1963. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28497532
TI  - Arabidopsis thaliana EPOXIDE HYDROLASE1 (AtEH1) is a cytosolic epoxide hydrolase
      involved in the synthesis of poly-hydroxylated cutin monomers.
AB  - Epoxide hydrolases (EHs) are present in all living organisms. They have been
      extensively characterized in mammals; however, their biological functions in
      plants have not been demonstrated. Based on in silico analysis, we identified
      AtEH1 (At3g05600), a putative Arabidopsis thaliana epoxide hydrolase possibly
      involved in cutin monomer synthesis. We expressed AtEH1 in yeast and studied its
      localization in vivo. We also analyzed the composition of cutin from A. thaliana
      lines in which this gene was knocked out. Incubation of recombinant AtEH1 with
      epoxy fatty acids confirmed its capacity to hydrolyze epoxides of C18 fatty acids
      into vicinal diols. Transfection of Nicotiana benthamiana leaves with constructs
      expressing AtEH1 fused to enhanced green fluorescent protein (EGFP) indicated
      that AtEH1 is localized in the cytosol. Analysis of cutin monomers in loss-of
      function Ateh1-1 and Ateh1-2 mutants showed an accumulation of 18-hydroxy-9,10
      epoxyoctadecenoic acid and a concomitant decrease in corresponding vicinal diols
      in leaf and seed cutin. Compared with wild-type seeds, Ateh1 seeds showed delayed
      germination under osmotic stress conditions and increased seed coat permeability
      to tetrazolium red. This work reports a physiological role for a plant EH and
      identifies AtEH1 as a new member of the complex machinery involved in cutin
      synthesis.

PMID- 28497533
TI  - The Saudi National Mental Health Survey: Methodological and logistical challenges
      from the pilot study.
AB  - Several challenges exist in carrying out nation-wide epidemiological surveys in
      the Kingdom of Saudi Arabia (KSA) due to the unique characteristics of its
      population. The objectives of this report are to review these challenges and the
      lessons learnt about best practices in meeting these challenges from the
      extensive piloting of the Saudi National Mental Health Survey (SNMHS), which is
      being carried out as part of the World Mental Health (WMH) Survey Initiative. We
      focus on challenges involving sample design, instrumentation, and data collection
      procedures. The SNMHS will ultimately provide crucial data for health policy
      makers and mental health specialists in KSA.

PMID- 28497535
TI  - Stimuli-Responsive Polymeric Nanoparticles.
AB  - There is increasing evidence that stimuli-responsive nanomaterials have become
      significantly critical components of modern materials design and technological
      developments. Recent advances in synthesis and fabrication of stimuli-responsive
      polymeric nanoparticles with built-in stimuli-responsive components (Part A) and
      surface modifications of functional nanoparticles that facilitate responsiveness
      (Part B) are outlined here. The synthesis and construction of stimuli-responsive
      spherical, core-shell, concentric, hollow, Janus, gibbous/inverse gibbous, and
      cocklebur morphologies are discussed in Part A, with the focus on shape, color,
      or size changes resulting from external stimuli. Although inorganic/metallic
      nanoparticles exhibit many useful properties, including thermal or electrical
      conductivity, catalytic activity, or magnetic properties, their assemblies and
      formation of higher order constructs are often enhanced by surface modifications.
      Section B focuses on selected surface reactions that lead to responsiveness
      achieved by decorating nanoparticles with stimuli-responsive polymers. Although
      grafting-to and grafting-from dominate these synthetic efforts, there are
      opportunities for developing novel synthetic approaches facilitating controllable
      recognition, signaling, or sequential responses. Many nanotechnologies utilize a
      combination of organic and inorganic phases to produce ceramic or metallic
      nanoparticles. One can envision the development of new properties by combining
      inorganic (metals, metal oxides) and organic (polymer) phases into one
      nanoparticle designated as "ceramers" (inorganics) and "metamers" (metallic).

PMID- 28497534
TI  - Effects of testosterone replacement therapy on metabolic syndrome among Japanese
      hypogonadal men: A subanalysis of a prospective randomised controlled trial
      (EARTH study).
AB  - We investigated the effects of testosterone replacement therapy (TRT) on
      metabolic factors among hypogonadal men with a metabolic syndrome. From the study
      population of the EARTH study, which was a randomised controlled study in Japan,
      65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n =
      32) and controls (n = 33), were included in this study analysis. The TRT group
      was administered 250 mg of testosterone enanthate as an intramuscular injection
      every 4 weeks for 12 months. Waist circumference, body mass index, body fat
      volume and blood pressure were measured in all patients at baseline and at 12
      months. In addition, blood biochemical data, including total cholesterol,
      triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin
      A1c (HbA1c) levels, were also evaluated. Changes in these categories from
      baseline to 12 months were compared between the TRT and control groups, with
      significant differences observed in waist circumference, body fat percentage,
      FPG, TG and HbA1c levels. No significant differences were observed in other
      parameters. TRT for 1 year was associated with improvements in some metabolic
      factors among Japanese men with hypogonadism and metabolic syndrome.

PMID- 28497536
TI  - Robotic guided waterjet cutting technique for high tibial dome osteotomy: A pilot
      study.
AB  - BACKGROUND: Oscillating saws generate high levels of heat (up to 150 degrees C),
      which can lead to tissue necrosis, delayed healing and infection. Abrasive
      waterjet-cutting techniques have been described as a new tool to perform bone
      cuts, with less heat generation. METHODS: Four lower-limbs of four human alcohol
      conserved cadavers were tested. Navigation references were attached to the tibia
      and an intraoperative fluoroscopy-based 3D scan was obtained. A 1.2 mm diameter
      nozzle was attached to a robotic arm, which was guided to follow a pre-specified
      path. In addition, a self-designed jet-absorber was applied to protect the
      posterior neurovascular structures. Magnesium was added as an abrasive substance
      to improve the cutting ability of the waterjet. RESULTS: In all four cadavers,
      the osteotomies could be carried out as planned, resulting in smooth cut
      surfaces. No damage to the soft-tissues was observed. CONCLUSIONS: The advantages
      of abrasive waterjet-cutting give it great potential in orthopaedic surgery. A
      current disadvantage is the amount of magnesium solute that is left on the
      surgical field and can be harmful to the patient.

PMID- 28497537
TI  - ICSH recommendations for modified and alternate methods measuring the erythrocyte
      sedimentation rate.
AB  - INTRODUCTION: The gold standard for the determination of the erythrocyte
      sedimentation rate (ESR) is the Westergren method. Other methods to measure the
      ESR have become available. They range from modest modifications of the Westergren
      method to very different methodologies. The ICSH therefore established a Working
      Group to investigate these new approaches and compile recommendations for their
      validation and verification. METHODS: A panel of six experts in laboratory
      hematology examined the peer-reviewed literature and EQA surveys from over 6000
      laboratories on four continents performing ESR testing. This information was used
      to create lists of ESR instrument manufacturers and their methods. RESULTS: Only
      28% of laboratories surveyed used the unmodified Westergren method, while 72% of
      sites used modified or alternate methods. Results obtained with the new
      instruments could differ from results obtained with the Westergren method by up
      to 142%. Different non-Westergren methods showed differences from each other of
      up to 42%. The new methods were often significantly faster, safer, and less labor
      intensive. They reduced costs and often used standard EDTA tubes, eliminating the
      need for a dedicated ESR tube. CONCLUSION: Based on the consensus of the Working
      Group, recommendations for manufacturers for the validation of new ESR methods
      were developed. In addition, a list of recommendations for laboratories that are
      moving to modified or alternate methods was compiled, addressing instrument
      performance verification and communications of results to clinical users.

PMID- 28497538
TI  - Multimodality imaging of a left ventricular aneurysm in a patient with normal
      coronary arteries: Unusual localization.
AB  - Left ventricular aneurysm (LVA) is rare but potentially fatal complication of
      myocardial infarction. It has been strictly defined as a distinct area of
      abnormal left ventricular diastolic contour with systolic dyskinesia or
      paradoxical bulging. It may be asymptomatic. However, complications including
      thromboembolism, heart failure, valvular regurgitation, arrhythmia, and rarely
      rupture may be the initial presentation. Diagnosis may be established by
      transthoracic echocardiography, left ventriculography, computed tomographic
      angiography, and cardiac magnetic resonance imaging. Here, we report a case of
      uncommonly located LVA in an adult patient with normal coronary arteries, which
      was diagnosed with multimodality imaging.

PMID- 28497539
TI  - Inverse-Electron-Demand Diels-Alder Reactions: Principles and Applications.
AB  - Inverse-electron-demand Diels-Alder (iEDDA) reactions are an intriguing class of
      cycloaddition reactions that have attracted increasing attention for their
      application in bioorthogonal chemistry, the total synthesis of natural products,
      and materials science. In many cases, the application of the iEDDA reaction has
      been demonstrated as an innovative approach to achieve target structures. The
      theoretical aspects of this class of reactions are of particular interest for
      scientists as a means to understand the various factors, such as steric strain
      and electron density of the attached groups, that govern the reaction and thus to
      elucidate the reaction mechanism. This review aims to summarize both theoretical
      investigations and application-driven research work on the iEDDA reaction. First,
      the historical aspects and the theoretical basis of the reaction, especially
      recent advances in time-dependent density functional theory (TD-DFT)
      calculations, as well as catalysis strategies will be highlighted and discussed.
      Second, the applications of this novel reaction in the context of materials
      science, bioorthogonal chemistry, and total synthesis of natural products will be
      elaborated with selected recent examples. The challenges and opportunities of the
      iEDDA reaction will be highlighted to give more insight into its potential
      applications in many other research areas.

PMID- 28497540
TI  - Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I.
AB  - In meiosis I, sister chromatids are captured by microtubules emanating from the
      same pole (mono-orientation), and centromeric cohesion is protected throughout
      anaphase. Shugoshin, which is localized to centromeres depending on the
      phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting
      meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore
      factor, meikin, may regulate cohesion protection, although the underlying
      molecular mechanisms remain elusive. Here, we show that fission yeast Moa1
      (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1
      (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to
      accumulate Bub1. Consequently, in contrast to the transient kinetochore
      localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until
      anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization
      and cohesion protection at centromeres by cooperating with heterochromatin
      protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic
      analyses show a hierarchical regulation of centromeric cohesion protection by
      meikin and shugoshin that is important for establishing meiosis-specific
      chromosome segregation. We provide evidence that the meiosis-specific Bub1
      regulation is conserved in mouse.

PMID- 28497541
TI  - The impact of body weight on the diagnosis of aortic dilation-misdiagnosis in
      overweight and underweight groups.
AB  - BACKGROUND: Body surface area (BSA)-indexed Z-scores are used to assess the
      ascending aorta (AAo) and diagnose aortic dilation (AoD) in children. BSA is
      directly related to body weight and corresponds to body mass index (BMI). We
      hypothesized extremes in BMI alter interpretation of aortic size in pediatric
      patients with AoD. METHODS: We reviewed all echocardiograms with a diagnosis of
      AoD performed at our institution from January 2013 through June 2013. Those with
      an age <2 or >20 years, history of aortic root surgery, or inadequate images were
      excluded. The aorta was measured by standard methods at the sinus of Valsalva,
      sinotubular junction, and proximal AAo. Using subject age, height, and gender,
      hypothetical weights for each subject were calculated to provide BMIs
      corresponding to the 5th, 50th, 85th, and 95th percentiles. The derived weights
      were then used to determine hypothetical BSA, and Z-scores were calculated for
      the subject's aortic diameters in each BMI group. RESULTS: A total of 153
      patients met inclusion criteria. Mean age was 11.1+/-4.6 years (68% male). Mean
      height was 142.7+/-27.9 cm, mean weight 44.6+/-24.8 kg, and mean true BMI was the
      62nd centile. Significant differences in all aortic dimension Z-scores were found
      among normal and underweight, overweight, and obese BMI groups (P<.001 for all
      comparisons), respectively. CONCLUSION: Using current recommended methods, AoD
      will be missed in overweight and obese patients and overdiagnosed in underweight
      patients. For children of normal weight, a Z-score based on BSA may be reliable.
      As obesity rates increase, weight-independent Z-scores must be developed.

PMID- 28497542
TI  - Molecular detection and phylogenetic analysis of hepatitis E virus strains
      circulating in wild boars in south-central Italy.
AB  - Hepatitis E virus (HEV) is a zoonotic pathogen with a worldwide distribution, and
      infects several mammalian species, including pigs and wild boars, which are
      recognized as its natural reservoirs. The virus causes a usually self-limiting
      liver disease with a mortality rate generally below 1%, although mortality rates
      of 15%-25% have been recorded in pregnant woman. Chronic infections can also
      occur. The prevalence of HEV has been extensively studied in wild boars and pigs
      in northern Italy, where intensive pig herds are predominantly located. In
      contrast, few data have been collected in south-central Italy, where small pig
      herds are surrounded by large regional parks populated with heterogeneous wild
      fauna. In this study, 291 liver samples from wild boars caught in south-central
      Italy were analysed with the molecular detection of viral RNA. Our results
      confirm the circulation of HEV in these animals, with a mean prevalence of 13.7%
      (40 of 291). A nucleotide sequence analysis showed that the HEV strains were
      highly conserved within the same geographic areas. The wild boar HEV strains
      belonged to the HEV-3c subtype, which is frequently described in wild boars, and
      to an uncommon undefined subtype (HEV-3j-like).The viral prevalence detected is
      concerning because it could represent a potential risk to hunters, meat workers
      and consumers of wild boar liver and derivative products. The hypothesized inter
      species transmission of HEV to pigs and the possibility that the virus maintains
      its virulence in the environment and the meat chain also present potential risks
      to human health, and warrant further investigations in the near future.

PMID- 28497543
TI  - Critical values in hematology of 862 institutions in China.
AB  - INTRODUCTION: A national survey on critical values in hematology of China
      laboratories was conducted to determine the current practice and assess the
      quality indicators so as to obtain a quality improvement. METHODS: Laboratories
      participating were asked to submit the general information, the practice of
      critical value reporting, and the status of timeliness of critical value
      reporting. RESULTS: A total of 862 laboratories submitted the results. The
      majority of participants have included white blood cell count, blood platelet
      count, hemoglobin, prothrombin time, and activated partial thromboplastin time in
      their critical value lists. Many sources are used for establishing a critical
      value policy, and some of the laboratories consult with clinicians. The
      unreported critical value rate, late critical value reporting rate, and
      clinically unacknowledged rate in China are relatively low, and the median of
      critical value reporting time is 8-9 minutes. CONCLUSION: There exists a wide
      variety for critical value reporting in hematology in China. Laboratories should
      establish a policy of critical value reporting suited for their own situations
      and consult with clinicians to set critical value lists. Critical values are
      generally reported in a timely manner in China, but some measures should be taken
      to further improve the timeliness of critical value reporting.

PMID- 28497544
TI  - Inducing unconscious stress: Cardiovascular activity in response to subliminal
      presentation of threatening and neutral words.
AB  - Stress-related cognitive processes may occur outside of awareness, here referred
      to as unconscious stress, and affect one's physiological state. Evidence
      supporting this idea would provide necessary clarification of the relationship
      between psychological stress and cardiovascular (CV) health problems. We tested
      the hypothesis that increases in mean arterial pressure (MAP) and total
      peripheral resistance (TPR) and decreases in heart rate variability (HRV) would
      be larger when threatening stimuli are presented outside of awareness, or
      subliminally, compared with neutral stimuli. Additionally, it was expected that
      trait worry and resting HRV, as common risk factors for CV disease, would
      moderate the effect. We presented a subliminal semantic priming paradigm to
      college students that were randomly assigned to the threat (n = 56) or neutral
      condition (n = 60) and assessed changes from baseline of MAP, TPR, and HRV. Level
      of trait worry was assessed with the Penn State Worry Questionnaire. The findings
      indicate that CV activity changed according to the hypothesized pattern: A higher
      MAP and TPR and a lower HRV in the threat condition compared with the neutral
      condition were found with practically meaningful effect sizes. However, these
      findings were only statistically significant for TPR. Furthermore, changes in CV
      activity were not moderated by trait worry or resting HRV. This is the first
      study to explicitly address the role of subliminally presented threat words on
      health-relevant outcome measures and suggests that unconscious stress can
      influence peripheral vascular resistance.

PMID- 28497545
TI  - Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste
      receptor, through the mTOR pathway in the mouse mammary gland.
AB  - SCOPE: Understanding the regulatory mechanism of milk protein synthesis is
      important to develop strategies to improve milk protein and enhance lactation
      performance. The mammalian target of rapamycin (mTOR) pathway is a crucial
      modulator of protein synthesis. In this study, we want to investigate if
      T1R1/T1R3 can regulate milk protein synthesis and mediate the mTOR pathway in the
      mice mammary gland in vivo. METHODS AND RESULTS: T1R1 knockout mice, WT mice, and
      mammary explants were used. The weigh-suckle-weigh method was used to quantify
      the milk yield. The expression level of beta-casein and AA transporter mRNA were
      analyzed by qPCR. Western blot was used to analyze protein abundance of members
      of the mTOR pathway. As expected, the knockout of T1R1 not only reduced the total
      milk yield in the mice mammary glands, but also repressed beta-casein synthesis.
      Additionally, the phosphorylation of 4EBP1 and S6K was significantly decreased in
      T1R1 knockout mice. The T1R1 knockout also increased the protein abundance of the
      AA transporter SLC3A2 and mRNA expression of SLC7A5/SLC3A2 and SLC1A5. Activation
      of the mTOR pathway was repressed by inhibition of T1R3 or T1R1 knockout in
      mammary gland explants. CONCLUSION: T1R1/T1R3 modulates the mTOR pathway to
      regulate milk protein synthesis in the mouse mammary gland in vivo.

PMID- 28497546
TI  - An error in the article by Oteri et al: 'Prescribing pattern of antipsychotic
      drugs during the years 1996-2010'.

PMID- 28497548
TI  - Erratum.

PMID- 28497549
TI  - A large scale prospective clinical and psychometric validation of the EORTC
      colorectal (QLQ-CR29) module in Polish patients with colorectal cancer.
AB  - The purpose of our study was to assess if the Polish translation of the European
      Organisation for Research and Treatment of Cancer (EORTC) Colorectal Cancer (CRC)
      Specific Quality of Life Questionnaire (QLQ-CR29) is an acceptable and
      psychometrically valid measure to collect quality of life (QoL) data in Polish
      patients with CRC for use in clinical trials and clinical practice. A total of
      150 patients undergoing treatment for CRC were prospectively enrolled in the
      study. Psychometric assessment of the translated QLQ-CR29 structure, reliability,
      convergent and divergent validity, and clinical validity was subsequently
      performed. The Cronbach's alpha coefficient ranged from 0.70-0.89, indicating
      acceptable internal consistency. For test-retest reliability, the ICCs for each
      item ranged from 0.59-0.91, with exceptions for urinary incontinence and dysuria,
      indicating good to excellent reproducibility. In multi-trait scaling analyses,
      the criterion for item convergent and divergent validity was satisfied. The
      correlations between the EORTC QLQ-CR29 and QLQ-C30 scales were mostly low (r <
      .40), with a few items demonstrating higher correlations. The known group
      comparisons analyses demonstrated the ability of the questionnaire to distinguish
      between patients' differing age, stoma status, and treatment intent. The Polish
      translation of the QLQ-CR29 is a psychometrically reliable and valid tool. The
      results of this study are congruent with that of EORTC validation.

PMID- 28497551
TI  - Proximity and gravity: modeling heaped self-reports.
AB  - Self-reported daily cigarette counts typically exhibit a preponderance of round
      numbers, a phenomenon known as heaping or digit preference. Heaping can be a
      substantial nuisance, as scientific interest lies in the distribution of the
      underlying true values rather than that of the heaped data. In principle, we can
      estimate parameters of the underlying distribution from heaped data if we know
      the conditional distribution of the heaped count given the true count, denoted
      the heaping mechanism (analogous to the missingness mechanism for missing data).
      In general, it is not possible to estimate the heaping mechanism robustly from
      heaped data only. A doubly-coded smoking cessation trial data set that includes
      daily cigarette count as both a conventional heaped retrospective recall
      measurement and a precise instantaneous measurement offers the rare opportunity
      to directly estimate the heaping mechanism. We propose a novel model that
      describes the conditional probability of the self-reported count as a function of
      its proximity to the truth and its intrinsic attractiveness, denoted its gravity.
      We apply variations of the model to the cigarette count data, illuminating the
      cognitive processes that influence self-reporting behaviors. The principal
      application of the model will be to enabling the correct analysis of heaped-only
      data sets. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28497550
TI  - Metagenomics analysis of red blood cell and fresh-frozen plasma units.
AB  - BACKGROUND: Although the risk of transmitting infectious agents by blood
      transfusion is dramatically reduced after donor selection, leukoreduction, and
      laboratory testing, some could still be present in donor's blood. A description
      of metagenomes in blood products eligible for transfusion represents relevant
      information to evaluate the risk of pathogen transmission by transfusion. STUDY
      DESIGN AND METHODS: Detection of viruses, bacteria, and fungi genomes was made by
      high-throughput sequencing (HTS) of 600 manufactured blood products eligible for
      transfusion: 300 red blood cell (RBC) and 300 fresh-frozen plasma (FFP) units.
      RESULTS: Anelloviruses and human pegivirus, frequent in the blood of healthy
      individuals, were found. Human papillomavirus type 27 and Merkel cell
      polyomavirus, present on the skin, were also detected. Unexpectedly, astrovirus
      MLB2 was identified and characterized in a FFP unit. The presence of astrovirus
      MLB2 was confirmed in donor's blood and corresponded to an asymptomatic acute
      viremia. Sequences of bacteria and fungi were also detected; they are likely the
      result of environmental contamination. CONCLUSION: This study demonstrates that
      HTS is a promising tool for detecting common and less frequent infectious
      pathogens in blood products.

PMID- 28497552
TI  - A novel porcine kobuvirus emerged in piglets with severe diarrhoea in China.
AB  - Since the first report of porcine kobuvirus (PKV) in 2008, it has been confirmed
      that PKV is widely present in several countries and plays an important role in
      diarrhoea outbreak in pigs. Studies have shown that the biggest difference among
      PKVs is the presence or absence of a specific 30-amino acid (aa) sequence in the
      2B region of the polyprotein gene. Based on this unique feature, most PKV
      sequences could be divided into two groups (Group 1 without deletion and Group 2
      with deletion), but a few sequences did not follow this rule due to possible
      recombination. In this study, two PKV genome sequences, designated JXAT2015
      (8,123 nucleotide) and JXJC2015 (8,120 nucleotide), were identified on two
      different commercial swine farms with the severe diarrhoea outbreak accompanying
      with highly PKV infection (90%, 18/20) and moderate infection (40%, 8/20) of
      porcine bocavirus 1 (PBoV1) in Jiangxi province of China. Sequence analysis based
      on the polyprotein gene showed that they shared low nucleotide similarity (86.3%
      88.1%) with other known PKVs. Although both possessed the 30-aa deletion in the
      2B region, phylogenetic analysis showed that JXJC2015 was distinct from Group 1
      and even Group 2, and formed a new Group (designated Group 3). The findings of
      this study further revealed genetic diversity and the possible pathogenic role of
      PKV in conjunction with other pathogens in piglets.

PMID- 28497553
TI  - Simultaneous transcatheter therapy for perimembranous ventricular septal defect
      combined with patent ductus arteriosus.
AB  - OBJECTIVE: This study aims to assess the clinical efficiency and safety of
      simultaneous transcatheter interventional treatment for perimembranous
      ventricular septal defect (pmVSD) combined with patent ductus arteriosus (PDA).
      METHODS: Twenty-five patients with pmVSD and PDA treated with simultaneous
      transcatheter interventions from April 2004 to December 2015 were included in
      this study. The mean age was 9.80 +/- 8.14 years and the mean weight was 29.76 +/
      14.82 Kg. Transthoracic echocardiography (TTE) and angiography were performed
      immediately after the procedure. Patients were re-examined by electrocardiogram,
      X-ray, and TTE at 2 days, 1 month, 3 months, and 6 months postoperatively.
      RESULTS: The interventional procedure was successfully performed in all 25
      patients. No intraoperative complication was noted. TTE examination of the VSD
      and PDA immediately after the procedure showed no residual shunt and the occluder
      was well positioned. Among these patients, four patients showed electrocardiogram
      changes after the procedure that resolved after drug therapy. The cardiothoracic
      ratio, left atrial diameter, left ventricular end-systolic diameter, and left
      ventricular end-diastolic diameter recovered to normal in most patients at 6
      months postoperatively. CONCLUSIONS: Simultaneously transcatheter interventional
      therapy is a safe and effective method for pmVSD combined with PDA.

PMID- 28497555
TI  - Multifunctional Free-Standing Gel Polymer Electrolyte with Carbon Nanofiber
      Interlayers for High-Performance Lithium-Sulfur Batteries.
AB  - Free-standing trimethylolpropane ethoxylate triacrylate gel polymer electrolyte
      is synthesized by a chemical cross-linking process and used as an electrolyte and
      separator membrane in lithium-sulfur batteries. The cross linked gel polymer
      electrolyte also exhibited a stable geometric size retention of 95 % at the high
      temperature of 130  degrees C. The as-prepared gel polymer electrolyte membrane
      with carbon nanofibers interlayer can effectively prevent polysulfide dissolution
      and shuttle effect, leading to significantly enhanced electrochemical properties,
      including high capacity and cycling stability, with an enhanced specific capacity
      of 790 mA h g-1 after 100 cycles.

PMID- 28497554
TI  - Shaking Up the Debate: Ensuring the Ethical Use of DBS Intervention Criteria for
      Mid-Stage Parkinson's Patients.
AB  - OBJECTIVES: Deep brain stimulation (DBS) is a well-established treatment for the
      management of severe motor fluctuations in advanced Parkinson's disease (PD).
      Until recently, device regulation, medical, and insurance practices limited DBS
      to patients with advanced stages of PD. In February 2016 this changed, however,
      when the US Food and Drug Administration (FDA) granted formal approval for the
      use of brain stimulator in mid-stage PD patients. In this article, we examine
      whether DBS in mid-stage PD can be ethically justified beyond the FDA approval.
      MATERIALS AND METHODS: We scrutinize the current risk-benefit profile, the costs
      benefit profile, and the capacity for informed consent requirement, to ask if use
      of subthalamic nucleus (STN) in mid-stage DBS is ethically appropriate. RESULTS:
      We propose that mid-stage DBS decisions could be appropriate under a shared
      decision-making model, which embraces a broad quality of life perspective.
      CONCLUSION: Although it might be too premature to know how the FDA decision will
      affect medical and insurance practices, we conclude by arguing that revisions to
      persisting guidelines seems justified both on scientific and ethical grounds.

PMID- 28497556
TI  - Mitral arcade: A rare case presenting with fatigue and cough.
AB  - An 11-year-old girl was admitted to pediatric emergency unit with complaints of
      fatigue and cough. The patient had no previous complaints. There was no history
      of rheumatic heart disease. The height and duration of the P-wave was 4 mm and
      0.16 seconds, respectively (p mitrale). Echocardiography showed enlarged left
      atrium (51*61 mm in diameter). Both the anterolateral and posteromedial papillary
      muscles were directly attached to the anterior and posterior mitral valve
      leaflets without tendinous chords. The patient was diagnosed with mitral arcade,
      severe mitral stenosis, and mitral regurgitation. The patient was referred to
      surgery for replacement of mitral valve.

PMID- 28497557
TI  - Acquiring research-grade ERPs on a shoestring budget: A comparison of a modified
      Emotiv and commercial SynAmps EEG system.
AB  - This study compared the performance of a low-cost wireless EEG system to a
      research-grade EEG system on an auditory oddball task designed to elicit N200 and
      P300 ERP components. Participants were 15 healthy adults (6 female) aged between
      19 and 40 (M = 28.56; SD = 6.38). An auditory oddball task was presented
      comprising 1,200 presentations of a standard tone interspersed by 300 trials
      comprising a deviant tone. EEG was simultaneously recorded from a modified Emotiv
      EPOC and a NeuroScan SynAmps RT EEG system. The modifications made to the Emotiv
      system included attaching research grade electrodes to the Bluetooth transmitter.
      Additional modifications enabled the Emotiv system to connect to a portable
      impedance meter. The cost of these modifications and portable impedance meter
      approached the purchase value of the Emotiv system. Preliminary analyses revealed
      significantly more trials were rejected from data acquired by the modified Emotiv
      compared to the SynAmps system. However, the ERP waveforms captured by the Emotiv
      system were found to be highly similar to the corresponding waveform from the
      SynAmps system. The latency and peak amplitude of N200 and P300 components were
      also found to be similar between systems. Overall, the results indicate that, in
      the context of an oddball task, the ERP acquired by a low-cost wireless EEG
      system can be of comparable quality to research-grade EEG acquisition equipment.

PMID- 28497558
TI  - Ectopic thyroid mass in the right ventricle: A case report.
AB  - Ectopic thyroid is a rare congenital embryonic anomaly. Ectopic thyroid tissue
      can be located anywhere during its descent, but it is found primarily at the base
      of the tongue and in the mediastinum. It is very rarely found in the heart. Here,
      we report a rare case of cardiac ectopic thyroid tissue in a 53-year-old woman
      who presented with chest pain. Echocardiography revealed an intracardiac mass
      that was removed successfully. Histopathology confirmed that the mass was thyroid
      tissue without malignancy.

PMID- 28497559
TI  - Macromolecular structures: Quality assessment and biological interpretation.
AB  - Structure determination using X-ray crystallography involves collection of
      diffraction data, determination of initial phases followed by iterative rounds of
      model building and crystallographic refinement to improve the phases and minimize
      the differences between calculated and observed structure factors. At each of
      these stages, a variety of statistical filters exist to ensure appropriate
      validation. Biologically important observations often come from interpretations
      of signals that need to be carefully deciphered from noise, and therefore human
      intervention is as important as the automated methods and filters. Currently, all
      structural data are deposited in the Protein Data Bank (PDB), and this repository
      is continuously evolving to incorporate new developments in macromolecular
      crystallography. The journals that publish data arising from structural studies
      modulate their policies to take cognizance of new improved methodologies.
      Together, the PDB and journals have evolved an accepted protocol to ensure the
      integrity of crystallographic results. As a result, the quality of available data
      and associated interpretations have improved over the years. Typically, if there
      are differences regarding the mechanism of action of a protein revealed by
      crystallography then new experiments are carried out to provide further evidence
      for or against a particular hypothesis. Hence, the scientific systems in
      structural biology are robust and to a large extent capable of correcting any
      errors in interpretation of structural results. However, this process is hindered
      by spurious challenges to published research, based on misuse of validation
      mechanisms. Such activities are counterproductive and will cause damage to the
      field of structural biology. (c) 2017 IUBMB Life, 69(8):563-571, 2017.

PMID- 28497560
TI  - Untargeted Metabolomic Analysis of Capsicum spp. by GC-MS.
AB  - INTRODUCTION: In order to conserve the biodiversity of Capsicum species and find
      genotypes with potential to be utilised commercially, Embrapa Clima Temperado
      maintains an active germplasm collection (AGC) that requires characterisation,
      enabling genotype selection and support for breeding programmes. OBJECTIVE: The
      objective of this study was to characterise pepper accessions from the Embrapa
      Clima Temperado AGC and differentiate species based on their metabolic profile
      using an untargeted metabolomics approach. MATERIAL AND METHODS: Cold (-20
      degrees C) methanol extraction residue of freeze-dried fruit samples was
      partitioned into water/methanol (A) and chloroform (B) fractions. The polar
      fraction (A) was derivatised and both fractions (A and B) were analysed by gas
      chromatography coupled to mass spectrometry (GC-MS). Data from each fraction was
      analysed using a multivariate principal component analysis (PCA) with XCMS
      software. RESULTS: Amino acids, sugars, organic acids, capsaicinoids, and
      hydrocarbons were identified. Outlying accessions including P116 (C. chinense),
      P46, and P76 (C. annuum) were observed in a PCA plot mainly due to their high
      sucrose and fructose contents. PCA also indicated a separation of P221 (C.
      annuum) and P200 (C. chinense), because of their high dihydrocapsaicin content.
      CONCLUSIONS: Although the metabolic profiling did not allow for grouping by
      species, it permitted the simultaneous identification and quantification of
      several compounds complementing and expanding the metabolic database of the
      studied Capsicum spp. in the AGC. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28497561
TI  - On assessing bioequivalence and interchangeability between generics based on
      indirect comparisons.
AB  - As more and more generics become available in the market place, the
      safety/efficacy concerns may arise as the result of interchangeably use of
      approved generics. However, bioequivalence assessment for regulatory approval
      among generics of the innovative drug product is not required. In practice,
      approved generics are often used interchangeably without any mechanism of safety
      monitoring. In this article, based on indirect comparisons, we proposed several
      methods to assessing bioequivalence and interchangeability between generics. The
      applicability of the methods and the similarity assumptions were discussed, as
      well as the inappropriateness of directly adopting adjusted indirect comparison
      to the field of generics' comparison. Besides, some extensions were given to take
      into consideration the important topics in clinical trials for bioequivalence
      assessments, for example, multiple comparisons and simultaneously testing
      bioequivalence among three generics. Extensive simulation studies were conducted
      to investigate the performances of the proposed methods. The studies of malaria
      generics and HIV/AIDS generics prequalified by the WHO were used as real examples
      to demonstrate the use of the methods. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28497562
TI  - Different aggregation states of a nuclear localization signal-tagged 25-kDa C
      terminal fragment of TAR RNA/DNA-binding protein 43 kDa.
AB  - The mechanism and cause of motor neuronal cell death in amyotrophic lateral
      sclerosis (ALS), a devastating neurodegenerative disorder, are unknown; gain of
      function of oligomers and aggregation of misfolded proteins, including carboxyl
      terminal fragments (CTFs) of TAR RNA/DNA-binding protein 43 kDa (TDP-43), have
      been proposed as important causative factors in the onset of ALS. We recently
      reported that a nuclear localization signal (NLS)-tagged 25-kDa CTF of TDP-43
      (TDP25) could decrease the cell-death proportion compared with that promoted by
      TDP25. Here, we show oligomeric states of NLS-TDP25 and its detailed localization
      property using super-resolution fluorescence microscopy, FRET, fluorescence
      recovery after photobleaching, and fluorescence correlation spectroscopy
      analysis. NLS-TDP25 efficiently formed a nucleolar cap structure via RNA binding
      in the presence of actinomycin D, but TDP25 did not. Although cytoplasmic
      inclusion bodies including TDP25 had a disordered and immobile structure, NLS
      TDP25 in the nucleolus was ordered and dynamic. In the diffuse state, TDP25
      formed fewer oligomers and interacted with the molecular chaperone, HSP70;
      however, NLS-TDP25 formed oligomers. These results suggested that NLS-tagged
      TDP25 can change its structure to use ordered oligomeric but nontoxic state.
      Moreover, the structure of ordered oligomers as well as nuclear sequestration may
      be important in mediating cytotoxicity in ALS pathology.

PMID- 28497563
TI  - Frequency of polycythemia in individuals with normal complete blood cell counts
      according to the new 2016 WHO classification of myeloid neoplasms.
AB  - INTRODUCTION: Polycythemia vera (PV) is a disorder characterized by clonal
      proliferation of myeloid cells and increased red blood cell mass. Recently, the
      revised 2016 WHO classification of myeloid neoplasms decreased the threshold
      levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new
      proposed cutoffs have remarkable overlap with the normal reference values
      reported and the clinical impact of these new cutoffs has not been widely
      assessed in the general population. METHODS: We retrospectively examined 248 839
      patients with presumptively normal complete blood cell results, consecutively
      obtained in an outpatient setting. RESULTS: The proportion of men with Hb >165
      g/L was 5.99%, Hct>49% was 2.4%, and Hb >165 g/dL or Hct>49% was 6.48%, while the
      proportion of women with Hb >160 g/L was 0.22%, Hct>48% was 0.11%, and Hb >160
      g/L or Hct>48% was 0.28%. CONCLUSION: The isolated use of the proposed Hb/Hct
      levels as a definer of polycythemia may lead to a substantial increase in
      unnecessary diagnostic tests. In cases with borderline levels of hemoglobin, the
      diagnostic workup of PV should only be indicated in the presence of clinical
      and/or laboratorial features associated with MPN.

PMID- 28497565
TI  - Transient left ventricular outflow tract obstruction with systolic anterior
      motion of the mitral valve: A stunning cause.
AB  - Left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion
      (SAM) of the mitral valve may have various etiologies, of which hypertrophic
      cardiomyopathy is the most common. More rarely, an acute coronary syndrome,
      myocardial stunning, and takotsubo cardiomyopathy may give rise to LVOTO and SAM.
      Here, we present a 70-year-old female patient with a non-ST-elevation acute
      coronary syndrome treated with percutaneous coronary intervention.
      Echocardiography the day after, because of dyspnea and hypotension, revealed
      apical akinesia, LVOTO, and SAM, which proved completely reversible after
      treatment with a beta-blocker and a 2-month follow-up period. It was concluded
      that postischemic apical stunning had caused LVOTO and SAM.

PMID- 28497564
TI  - No significant enrichment of rare functionally defective CPA1 variants in a large
      Chinese idiopathic chronic pancreatitis cohort.
AB  - Rare functionally defective carboxypeptidase A1 (CPA1) variants have been
      reported to predispose to nonalcoholic chronic pancreatitis, mainly the
      idiopathic subtype. However, independent replication has so far been lacking,
      particularly in Asian cohorts where initial studies employed small sample sizes.
      Herein we performed targeted next-generation sequencing of the CPA1 gene in 1,112
      Han Chinese idiopathic chronic pancreatitis (ICP) patients-the largest ICP cohort
      so far analyzed in a single population-and 1,580 controls. Sanger sequencing was
      used to validate called variants, and the CPA1 activity and secretion of all
      newly found variants were measured. A total of 18 rare CPA1 variants were
      characterized, 11 of which have not been previously described. However, no
      significant association was noted with ICP irrespective of whether all rare
      variants [20 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in
      controls; P = 0.57] or functionally impaired variants [three out of 1,112 (0.27%)
      in patients vs. two out of 1,580 (0.13%) in controls; P = 0.68] were considered.

PMID- 28497566
TI  - CEST MRI of 3-O-methyl-D-glucose on different breast cancer models.
AB  - PURPOSE: To test the ability of chemical exchange saturation transfer (CEST) MRI
      of 3-O-methyl-D-glucose (3OMG) to detect tumors in several breast cancer models
      of murine and human origin, for different routes of administration of the agent
      and to compare the method with glucoCEST and with 18 FDG-PET on the same animals.
      METHODS: In vivo CEST MRI experiments were performed with a 7T Biospec animal MRI
      scanner on implanted orthotopic mammary tumors of mice before and after
      administration of 3OMG. RESULTS: A marked 3OMG-CEST MRI contrast that was
      correlated with the administrated dose was obtained in different breast cancer
      models and by intravenous, intraperitoneal, and per os methods of administration.
      The most aggressive breast cancer model yielded the highest CEST contrast. 3OMG
      CEST contrast reached its maximum at 20 min after administration and lasted for
      more than an hour, while that of glucose was lower and diminished after 20 min.
      3OMG-CEST showed comparable results to that of FDG PET. CONCLUSION: The
      sensitivity of the 3OMG-CEST MRI method indicates its potential for the detection
      of tumors in the clinic. Magn Reson Med 79:1061-1069, 2018. (c) 2017
      International Society for Magnetic Resonance in Medicine.

PMID- 28497567
TI  - Determination of disease phenotypes and pathogenic variants from exome sequence
      data in the CAGI 4 gene panel challenge.
AB  - The use of gene panel sequence for diagnostic and prognostic testing is now
      widespread, but there are so far few objective tests of methods to interpret
      these data. We describe the design and implementation of a gene panel sequencing
      data analysis pipeline (VarP) and its assessment in a CAGI4 community experiment.
      The method was applied to clinical gene panel sequencing data of 106 patients,
      with the goal of determining which of 14 disease classes each patient has and the
      corresponding causative variant(s). The disease class was correctly identified
      for 36 cases, including 10 where the original clinical pipeline did not find
      causative variants. For a further seven cases, we found strong evidence of an
      alternative disease to that tested. Many of the potentially causative variants
      are missense, with no previous association with disease, and these proved the
      hardest to correctly assign pathogenicity or otherwise. Post analysis showed that
      three-dimensional structure data could have helped for up to half of these cases.
      Over-reliance on HGMD annotation led to a number of incorrect disease
      assignments. We used a largely ad hoc method to assign probabilities of
      pathogenicity for each variant, and there is much work still to be done in this
      area.

PMID- 28497568
TI  - Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated
      at a single center.
AB  - Joubert syndrome (JS) is a genetically heterogeneous ciliopathy characterized by
      hypo-dysplasia of the cerebellar vermis, a distinct hindbrain/midbrain
      malformation (molar tooth sign), and intellectual disability. We evaluated the
      neuropsychological profiles of 76 participants with JS in the context of
      molecular genetics and clinical covariates. Evaluations included
      neuropsychological testing, structured parental interviews, DNA sequencing, brain
      magnetic resonance imaging (MRI), electroencephalography (EEG), ophthalmologic
      examination, and assessment for renal and hepatic disease. On average,
      participants manifested Full Scale Intelligence Quotients (FSIQ) in the
      moderately to profoundly low range (M = 64.3 +/- 15.3). Of the Wechsler index
      scores, verbal comprehension was least affected and processing speed was most
      affected. Receptive language was rated as better than expressive language on the
      Vineland Adaptive Behavior Scales-Second Edition. Those with abnormal EEG had a
      significantly lower FSIQ (n = 15; M = 50.7 +/- 12.9) compared to participants
      with normal EEG (n = 39; M = 64.7 +/- 16.3; p = .004). Participants taking
      psychiatric medications manifested a lower FSIQ (n = 20; M = 54.8 +/- 13.2) than
      those not taking them (n = 42; M = 65.0 +/- 17.2; p = .022). These correlations
      were also present in the TMEM67-related JS sub-cohort (n = 14). Based on parental
      assessment, psychiatric and behavioral problems were significantly more common
      than in the general population for all measures (p < .004 for all). The majority
      (65%) of individuals with JS have some degree of intellectual disability.
      Abnormal EEG is associated with lower neuropsychological function. Processing
      speed is a weakness, while verbal comprehension and receptive language are
      relative strengths. These findings may guide parents, teachers, therapists, and
      doctors to determine appropriate therapies, accommodations, and academic goals
      for individuals with JS.

PMID- 28497569
TI  - Early Onset of Efficacy and Consistency of Response Across Multiple Migraine
      Attacks From the Randomized COMPASS Study: AVP-825 Breath Powered(r) Exhalation
      Delivery System (Sumatriptan Nasal Powder) vs Oral Sumatriptan.
AB  - OBJECTIVE: To further characterize the clinical utility of AVP-825 based on
      additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3
      comparative efficacy trial of AVP-825 vs 100 mg oral sumatriptan (NCT01667679).
      AVP-825 was approved in January 2016 by the US Food and Drug Administration under
      the name ONZETRA(r) Xsail(r) (sumatriptan nasal powder) for the acute treatment
      of migraine with or without aura in adults. BACKGROUND: AVP-825 is a delivery
      system that uses a patient's own breath to deliver low-dose sumatriptan powder to
      the upper posterior regions of the nasal cavity beyond the narrow nasal valve,
      areas lined with vascular mucosa conducive to rapid drug absorption into the
      systemic circulation. The recommended dose of AVP-825 is 22 mg sumatriptan powder
      administered as one 11 mg nosepiece in each nostril, which delivers approximately
      15-16 mg of sumatriptan intranasally. The COMPASS trial compared AVP-825 22-100
      mg oral sumatriptan across multiple migraine attacks for efficacy, safety, and
      tolerability endpoints. DESIGN/METHODS: COMPASS was a randomized, multicenter,
      double-dummy, crossover, multiattack, comparative efficacy study with two 12-week
      double-blind periods. Patients with 2-8 migraine attacks/month were randomized
      1:1 to AVP-825 (22 mg) plus oral placebo or an identical placebo delivery system
      plus 100 mg oral sumatriptan for the first period, and then patients switched
      treatments for the second period. Patients treated up to 5 qualifying migraines
      per period within 1 h of onset, even if the intensity of the attack was mild.
      Results from the primary endpoint (SPID-30, defined as the sum of pain intensity
      differences from dosing to 30 minutes), key secondary efficacy endpoints and
      safety assessments have been reported in the primary publication (Tepper et al.,
      2015). This article reports additional prespecified outcomes, including the SPID
      30 for attacks treated when baseline severity was mild vs moderate/severe,
      measures of sustained response and consistency of effect in patients who
      experienced multiple migraine attacks, and the results of post hoc analyses
      performed to assess total migraine freedom (defined as no pain and no migraine
      associated symptoms, including nausea, vomiting, photophobia, and phonophobia),
      time to pain freedom, time to meaningful pain relief, and local (occurring at the
      site of administration in the nose) vs systemic treatment-emergent adverse events
      (TEAEs). RESULTS: A total of 185 patients completed both treatment periods,
      yielding 1,531 migraine attacks which were treated and assessed (765 AVP-825, 766
      oral sumatriptan). Treatment with AVP-825 provided greater reduction in migraine
      pain intensity which was statistically significant vs oral sumatriptan in the
      first 30 minutes postdose regardless of whether attacks were treated when pain
      was mild (least squares mean SPID-30 = 3.90 vs 0.24, P = .0013) or
      moderate/severe (least squares mean SPID-30 = 13.83 vs 10.07, P = .0002). At
      every time point from 15 to 90 minutes postdose, the proportion of attacks
      achieving total migraine freedom was greater and statistically significant after
      treatment with AVP-825 vs 100 mg oral sumatriptan. AVP-825 treatment resulted in
      greater odds of achieving pain freedom (odds ratio, OR = 1.29, P < .01) and
      meaningful pain relief (OR = 1.32, P < .0001), which were also statistically
      significant compared with oral sumatriptan. In addition, a greater proportion of
      attacks treated with AVP-825 vs oral sumatriptan was associated with sustained
      pain freedom, achieving statistical significance when assessed from 1 h postdose
      through 24 hours postdose (33.3% vs 27.9%; P < .05) and through 48 hours postdose
      (32.7% vs 27.4%; P < .05). For patients who treated multiple migraine attacks in
      both treatment periods, a greater proportion had consistent pain relief and pain
      freedom following treatment with AVP-825 compared to oral sumatriptan across
      multiple attacks, a difference that achieved statistical significance at 30
      minutes postdose. Local TEAEs of abnormal taste and nasal discomfort were more
      common following AVP-825 treatment. Of the patients experiencing either of these
      TEAEs, about 90% described the intensity as mild, and only one discontinued
      treatment because of either of these two TEAEs. CONCLUSIONS: These results from
      the COMPASS study further demonstrate that treatment with AVP-825 provides
      earlier onset and more consistent across-episode improvement of pain and migraine
      associated symptoms compared with oral sumatriptan, highlighting the clinical
      advantages of this newly approved intranasal delivery system for low-dose
      sumatriptan powder.

PMID- 28497570
TI  - LAPS Insulin115: A novel ultra-long-acting basal insulin with a unique action
      profile.
AB  - AIMS: To conduct a comprehensive pre-clinical study of the novel ultra-long
      acting insulin analogue LAPS Insulin115. METHODS: Pharmacokinetic/pharmacodynamic
      studies comparing LAPS Insulin115 with other basal insulins were conducted in
      genetically diabetic (db/db) mice. Insulin signalling in the major target organs
      was analysed using Western blot after single subcutaneous injection in wild-type
      male Wistar rats. Using in vitro assays we analysed transendothelial transport,
      insulin receptor (IR) interaction, and the mitogenic and metabolic properties of
      LAPS Insulin115. Furthermore, IR downregulation after long-term exposure to high
      concentrations of LAPS Insulin115 was analysed using an in vitro
      desensitization/resensitization model. RESULTS: The novel Fc-conjugated insulin
      derivative LAPS Insulin115 showed an extensively prolonged pharmacokinetic and
      pharmacodynamic profile in rodents. Despite its size of 59 kDa, LAPS Insulin115
      passes the vascular endothelial barrier and induces insulin signalling in all
      major target tissues in rats. In vitro, LAPS Insulin115 showed a very slow onset
      of action because of its reduced IR affinity; however, after long-term
      stimulation it was equipotent in respect to its metabolic potency and showed no
      increased mitogenic action when compared with regular insulin. Remarkably, under
      conditions of chronic exposure, LAPS Insulin115 does not induce irreversible
      desensitization of target cells, which is probably attributable to much less
      prominent IR downregulation. CONCLUSION: Thus, LAPS Insulin115 exhibits a unique
      in vivo and in vitro profile and thereby represents an excellent candidate for a
      once-weekly insulin analogue.

PMID- 28497571
TI  - Determination of strobilurin fungicide residues in fruits and vegetables by
      nonaqueous micellar electrokinetic capillary chromatography with indirect laser
      induced fluorescence.
AB  - A nonaqueous micellar electrokinetic capillary chromatography method with
      indirect LIF was developed for the determination of strobilurin fungicide
      residues in fruits and vegetables. Hydrophobic CdTe quantum dots (QDs)
      synthesized in aqueous phase were used as background fluorescent substance. The
      BGE solution, QD concentration, and separation voltage were optimized to obtain
      the best separation efficiency and the highest signal intensity. The optimal BGE
      solution consists of 40 mM phosphate, 120 mM sodium dodecyl sulfate, 15% v/v
      water and 15% v/v hydrophobic CdTe QDs in formamide, of which apparent pH is 9.5.
      The optimized separation voltage is controlled as 25 kV. The resultant detection
      limits of azoxystrobin, kresoxim-methyl, and pyraclostrobin are all 0.001 mg/kg,
      their linear dynamic ranges are 0.005-2.5 mg/kg, and the recoveries of the spiked
      samples are 81.7-96.1%, 86.5-95.7%, and 87.3-97.4%, respectively. This method has
      been proved to be sensitive enough to detect the aforementioned fungicides in
      fruits and vegetables at the maximum residue limits.

PMID- 28497572
TI  - Relationship between red blood cell distribution width, bilirubin, and clinical
      characteristics of patients with gastric cancer.
AB  - INTRODUCTION: Red blood cell distribution width (RDW) and bilirubin have been
      proved to be prognostic factors for various types of cancer. However, their
      prognostic value in patients with gastric cancer (GC) remains largely unknown.
      METHODS: To verify whether RDW and bilirubin are prognostic factors for patients
      with GC, we performed a cross-sectional study to analyze the relationship between
      RDW, bilirubin, and the clinical characteristics of patients with GC. Medical
      records of all newly diagnosed and pathologically proved patients with GC
      admitted to Changzheng Hospital between January 2016 and July 2016 were
      retrospectively reviewed. The relationship between RDW, bilirubin, and the
      clinical characteristics of patients with GC was analyzed. RESULTS: A total of
      144 patients with GC were enrolled. Patients with GC had significantly higher RDW
      than healthy controls, even after adjusting for hemoglobin, while total bilirubin
      (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly
      decreased. Furthermore, RDW and bilirubin were significantly correlated with
      tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen
      19-9 (CA19-9). CONCLUSION: Our study indicated that RDW and bilirubin could be
      potential prognostic factors for patients of GC.

PMID- 28497573
TI  - Simplex-based optimization of numerical and categorical inputs in early
      bioprocess development: Case studies in HT chromatography.
AB  - Bioprocess development studies often involve the investigation of numerical and
      categorical inputs via the adoption of Design of Experiments (DoE) techniques. An
      attractive alternative is the deployment of a grid compatible Simplex variant
      which has been shown to yield optima rapidly and consistently. In this work, the
      method is combined with dummy variables and it is deployed in three case studies
      wherein spaces are comprised of both categorical and numerical inputs, a
      situation intractable by traditional Simplex methods. The first study employs in
      silico data and lays out the dummy variable methodology. The latter two employ
      experimental data from chromatography based studies performed with the filter
      plate and miniature column High Throughput (HT) techniques. The solute of
      interest in the former case study was a monoclonal antibody whereas the latter
      dealt with the separation of a binary system of model proteins. The implemented
      approach prevented the stranding of the Simplex method at local optima, due to
      the arbitrary handling of the categorical inputs, and allowed for the concurrent
      optimization of numerical and categorical, multilevel and/or dichotomous, inputs.
      The deployment of the Simplex method, combined with dummy variables, was
      therefore entirely successful in identifying and characterizing global optima in
      all three case studies. The Simplex-based method was further shown to be of
      equivalent efficiency to a DoE-based approach, represented here by D-Optimal
      designs. Such an approach failed, however, to both capture trends and identify
      optima, and led to poor operating conditions. It is suggested that the Simplex
      variant is suited to development activities involving numerical and categorical
      inputs in early bioprocess development.

PMID- 28497574
TI  - Protein destabilization and loss of protein-protein interaction are fundamental
      mechanisms in cblA-type methylmalonic aciduria.
AB  - Mutations in the human MMAA gene cause the metabolic disorder cblA-type
      methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction
      remains lacking. MMAA regulates the incorporation of the cofactor
      adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the
      destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends
      on its GTPase activity, which is stimulated by an interaction with MUT. Here, we
      present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We
      biochemically investigated how missense mutations in MMAA in 22 patients lead to
      disease. About a third confer instability to the recombinant protein in bacterial
      and human expression systems. All 15 purified mutant proteins demonstrated wild
      type like intrinsic GTPase activity and only one (p.Asp292Val), where the
      mutation is in the GTP binding domain, revealed decreased GTP binding. However,
      all mutations strongly decreased functional association with MUT by reducing
      GTPase activity stimulation upon incubation with MUT, while nine mutant proteins
      additionally lost the ability to physically bind MUT. Finally, all mutations
      interfered with gating the transfer of AdoCbl from MMAB to MUT. This work
      suggests loss of functional interaction between MMAA and MUT as a disease-causing
      mechanism that impacts processing and assembly of a cofactor to its destination
      enzyme.

PMID- 28497575
TI  - Recognition of Delirium in Postoperative Elderly Patients: A Multicenter Study.
AB  - OBJECTIVES: To evaluate to what extent delirium experts agree on the diagnosis of
      delirium when independently assessing exactly the same information and to
      evaluate the sensitivity of delirium screening tools in routine daily practice of
      clinical nurses. DESIGN: Prospective observational longitudinal study. SETTING:
      Three medical centers in the Netherlands. PARTICIPANTS: Elderly postoperative
      adults (n = 167). MEASUREMENTS: A researcher examined participants daily
      (Postoperative Day 1-3) for delirium using a standardized cognitive assessment
      and interview including the Delirium Rating Scale Revised-98 as global impression
      without any cut-off values that was recorded on video. Two delirium experts
      independently evaluated the videos and clinical information from the last 24
      hours in the participants' record and classified each assessment as delirious,
      possibly delirious, or not delirious. Interrater agreement between the delirium
      experts was determined using weighted Cohen's kappa. When there was no consensus,
      a third expert was consulted. Final classification was based on median score and
      compared with the results of the Confusion Assessment Method for Intensive Care
      Unit and Delirium Observation Scale that clinical nurses administered. RESULTS:
      Four hundred twenty-four postoperative assessments of 167 participants were
      included. The overall kappa was 0.61 (95% confidence interval = 0.53-0.68). There
      was no agreement between the experts for 89 (21.0%) assessments and a third
      delirium expert was needed for the final classification. Delirium screening that
      nurses performed detected 32% of the assessments that the experts diagnosed as
      (possibly) delirious. CONCLUSION: There was considerable disagreement in
      classification of delirium by experts who independently assessed exactly the same
      information, showing the difficulty of delirium diagnosis. Furthermore, the
      sensitivity of daily delirium screening by clinical nurses was poor. Future
      research should focus on development of objective instruments to diagnose
      delirium.

PMID- 28497577
TI  - Least speciose among the most speciose: Natural history correlates of
      monospecific and bispecific genera of Rodentia and Soricomorpha.
AB  - Monospecific and bispecific genera are of special concern as they represent
      unique phylogenetic/evolutionary trajectories within larger clades. In addition,
      as phylogenetically older taxa are supposed to be exposed to higher rarity and
      extinction risk, monospecific and bispecific genera may be intrinsically more
      prone to extinction risks than multispecies genera, although extinction risks
      also depend on the ecological and biological strategy of the species. Here, the
      distribution across biogeographical zones and the levels of threat to 2 speciose
      orders of mammals (monospecific and bispecific genera of Rodentia and
      Soricomorpha) are investigated in order to highlight major patterns at the
      worldwide scale. In Rodentia, 39.7% of the genera (n = 490) were monospecific and
      17.9% were bispecific. In Soricomorpha, 44.4% of the total genera (n = 45) were
      monospecific and 15% were bispecific. There was a positive correlation between
      the number of monospecific genera and the total number of genera per family.
      Peaks of monospecific and bispecific genera richness were observed in
      Neotropical, Oriental and Afrotropical regions in rodents and in the Palearctic
      region in soricomorphs. Range size was significantly uneven across biogeographic
      region in rodents (with larger ranges in Nearctic and Oriental regions and
      smaller ranges in the Australian region), but there was no difference across
      biogeographic regions in terms of range size in soricomorphs. Most of the
      monospecific and bispecific genera occurred in forest habitat in both taxa. The
      frequency distribution of the monospecific and bispecific genera across IUCN
      categories did not differ significantly from the expected pattern using the total
      rodent genera and the multispecies genera.

PMID- 28497576
TI  - The space where aging acts: focus on the GABAergic synapse.
AB  - As it was established that aging is not associated with massive neuronal loss, as
      was believed in the mid-20th Century, scientific interest has addressed the
      influence of aging on particular neuronal subpopulations and their synaptic
      contacts, which constitute the substrate for neural plasticity. Inhibitory
      neurons represent the most complex and diverse group of neurons, showing distinct
      molecular and physiological characteristics and possessing a compelling ability
      to control the physiology of neural circuits. This review focuses on the aging of
      GABAergic neurons and synapses. Understanding how aging affects synapses of
      particular neuronal subpopulations may help explain the heterogeneity of aging
      related effects. We reviewed the literature concerning the effects of aging on
      the numbers of GABAergic neurons and synapses as well as aging-related
      alterations in their presynaptic and postsynaptic components. Finally, we
      discussed the influence of those changes on the plasticity of the GABAergic
      system, highlighting our results concerning aging in mouse somatosensory cortex
      and linking them to plasticity impairments and brain disorders. We posit that
      aging-induced impairments of the GABAergic system lead to an
      inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond
      with plastic changes to environmental and cellular challenges, leaving the brain
      more vulnerable to cognitive decline and damage by synaptopathic diseases.

PMID- 28497578
TI  - Effector and regulatory dendritic cells display distinct patterns of miRNA
      expression.
AB  - INTRODUCTION: MicroRNAs (miRNAs) contribute to the regulation of dendritic cell
      (DC) polarization, thereby influencing the balance of adaptive immune responses.
      Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether
      expression of these miRNAs could be associated with allergic rhinitis and
      allergen immunotherapy (AIT) outcome. METHOD: Using specific culture conditions,
      we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg
      subsets (supporting the differentiation of TH 1, TH 2 or regulatory T cells,
      respectively). Profiling of miRNA expression was performed in these DC
      subpopulations using microarrays. Levels of miRNAs specific for polarized DCs
      were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non
      allergic controls, as well as in samples from 30 subjects treated with sublingual
      grass pollen tablets or placebo for four months. RESULTS: We successfully
      identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and
      DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of
      those miRNAs (miR-132 and miR-155), was down-regulated compared to non-allergic
      individuals. However, the levels of these miRNAs were not significantly modified
      following four months of grass pollen immunotherapy. CONCLUSIONS: Studying
      polarized DCs and clinical samples from subjects with or without allergic
      rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to
      effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients
      with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent
      relevant biomarkers to predict or follow-up AIT efficacy.

PMID- 28497580
TI  - The evaluation of the relevance of thrombin generation and procoagulant activity
      in thrombotic risk assessment in BCR-ABL-negative myeloproliferative neoplasm
      patients.
AB  - INTRODUCTION: It has been recently suggested that microparticles (MP) play a role
      in the pathogenesis of thrombotic complications. This study aimed to assess the
      contribution of procoagulant activity expressed by circulating MP in thrombotic
      events in MPN patients. METHODS: Seventy-four MPN patients were enrolled in a
      trans-sectional study. The MP procoagulant activity was measured using two
      assays: (i) the thrombin generation (TG) assay used in different conditions with
      the addition of both tissue factor (TF) and phospholipids (PL) and with the
      addition of TF or PL alone and (ii) the PROCOAG-PPL assay. RESULTS: The mean age
      was 62 (26 men and 48 women). The prevalence of thrombotic events was 28%. When
      comparing patients with thrombosis to those without, age, sex, MPN type,
      cardiovascular risk factors, and history of thrombosis were not significantly
      associated with thrombosis. The JAK2 V617F mutation was significantly associated
      with thrombotic events (90% vs 67%; P=.04). Results from the TG assay and the
      PROCOAG-PPL assays did not demonstrate a significant association between the MP
      procoagulant activity and thrombotic events. CONCLUSION: The MP procoagulant
      activity did not predict thrombosis in MPN patients. The contribution of TG assay
      in the assessment of the thrombotic risk is still in debate.

PMID- 28497581
TI  - What could cognitive capital mean for China's children?
AB  - Cognitive capital is an emerging paradigm that captures the criticality of
      investing in children whilst neural proliferation and development of brain
      architecture are at their peak. Distinct from financial capital, cognitive
      capital represents investment in future human potential from interventions in
      nutrition, health, education, child protection, and social welfare systems that
      optimize brain development. The return on investment is significant given the
      plasticity of the developing brain in response to positive stimuli. Investment in
      brain development results in improved health and well-being, educational
      outcomes, skills, employment, and quality of life. The inverse is also true.
      Negative stimuli lead to depreciating cognitive capital, poorer mental and
      physical health and educational outcomes, and decreased life chances. Cognitive
      capital could be an organizing framework for China's next phase of development to
      ensure the building of a prosperous society. Through significant commitment from
      the government, China has seen remarkable improvements in under-five mortality,
      literacy rates, access to basic education, life expectancy, and gross domestic
      product in the past few decades as the result of an expansion of publicly funded
      social services. Yet, inequities remain within and across communities and
      regions. In 2015, China had a country ranking of 97 for gross national income per
      capita, highlighting remaining challenges across the whole population. Cognitive
      capital relies on a package of forward-looking policies that lead to equitable,
      efficient, and effective use of existing and future resources. This is consistent
      with the United Nations Convention on the Rights of the Child. Investments in
      interventions that maximize optimal brain development in children, realize
      children's rights, and contribute to future economic growth, defined as
      "cognitive capital," represent a significant opportunity for improving children's
      lives, nation-building, and future economic growth in China.

PMID- 28497579
TI  - Modulation of basal cell fate during productive and transforming HPV-16 infection
      is mediated by progressive E6-driven depletion of Notch.
AB  - In stratified epithelia such as the epidermis, homeostasis is maintained by the
      proliferation of cells in the lower epithelial layers and the concomitant loss of
      differentiated cells from the epithelial surface. These differentiating
      keratinocytes progressively stratify and form a self-regenerating multi-layered
      barrier that protects the underlying dermis. In such tissue, the continual loss
      and replacement of differentiated cells also limits the accumulation of oncogenic
      mutations within the tissue. Inactivating mutations in key driver genes, such as
      TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the
      long-term persistence of expanding mutant clones in the tissue. Here we show that
      through the expression of E6, HPV-16 prevents the early fate commitment of human
      keratinocytes towards differentiation and confers a strong growth advantage to
      human keratinocytes. When E6 is expressed either alone or with E7, it promotes
      keratinocyte proliferation at high cell densities, through the combined
      inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6
      is restricted to the basal layer of the epithelium and is enhanced during the
      progression from productive to abortive or transforming HPV-16 infection.
      Consistent with this, the expression of p53 and cleaved Notch1 becomes
      progressively more disrupted, and is associated with increased basal cell density
      and reduced commitment to differentiation. The expression of cleaved Notch1 is
      similarly disrupted also in HPV-16-positive cervical lesions, depending on
      neoplastic grade. When taken together, these data depict an important role of
      high-risk E6 in promoting the persistence of infected keratinocytes in the basal
      and parabasal layers through the inactivation of gene products that are commonly
      mutated in non-HPV-associated neoplastic squamous epithelia. (c) 2017 The
      Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of
      Pathological Society of Great Britain and Ireland.

PMID- 28497582
TI  - An objective definition for clinical suspicion of T-cell-mediated rejection after
      liver transplantation.
AB  - A uniform definition of clinical suspicion of T-cell-mediated rejection (TCMR) in
      liver transplantation (LT) is needed to homogenize clinical decisions, especially
      within randomized trials. This multicenter study included a total of 470 primary
      LT recipients. The derivation cohort consisted of 142 patients who had clinically
      driven liver biopsies at any time after LT. The external validation cohort
      included 328 patients who underwent protocol biopsies at day 7-10 after LT. The
      rates of moderate-severe histological TCMR were 33.8% in the derivation cohort
      and 43.6% in the validation cohort. Independent predictors (ie, risk factors) of
      moderate-severe TCMR in the derivation cohort were as follows: serum bilirubin >4
      mg/dL (OR=5.83; P<.001), rising bilirubin within the 4 days prior to liver biopsy
      (OR=4.57; P=.003), and blood eosinophils count >0.1*109 /L (OR=3.81; P=.004). In
      the validation cohort, the number of risk factors was an independent predictor of
      moderate-severe TCMR (OR=1.74; P=.001), after controlling for hepatitis C status.
      The number of risk factors paralleled the rates of moderate-severe TCMR in the
      derivation and validation cohorts (P<.001 in both comparisons). In conclusion,
      increased serum bilirubin, rising bilirubin and eosinophilia are validated risk
      factors for moderate-severe histological TCMR and could be used as objective
      criteria to select candidates for liver biopsy.

PMID- 28497583
TI  - Evaluation of athletes with complex congenital heart disease.
AB  - As a result of improvements in congenital heart surgery, there are more adults
      alive today with congenital heart disease (CHD) than children. Individuals with
      cardiac birth defects may be able to participate in physical activities but
      require proper cardiovascular evaluation. The American Heart Association and
      American College of Cardiology released guidelines in 2015 for athletes with
      cardiovascular abnormalities. The guidelines express that although restriction
      from competitive athletics may be indicated for some, the majority of individuals
      with CHD can and should engage in some form of physical activity. This case study
      demonstrates the importance of combining all aspects of history, physical
      examination, ECG, and imaging modalities to evaluate cardiac anatomy and function
      in young athletes with complex CHD.

PMID- 28497584
TI  - Recommended practice for laboratory reporting of non-invasive prenatal testing of
      trisomies 13, 18 and 21: a consensus opinion.
AB  - OBJECTIVE: Non-invasive prenatal testing (NIPT) for trisomies 13, 18 and 21 is
      used worldwide. Laboratory reports should provide clear, concise results with
      test limitations indicated, yet no national or local guidelines are currently
      available. Here, we aim to present minimum best practice guidelines. METHODS: All
      laboratories registered in the three European quality assurance schemes for
      molecular and cytogenetics were invited to complete an online survey focused on
      services provided for NIPT and non-invasive prenatal diagnosis. Laboratories
      delivering NIPT for aneuploidy were asked to submit two example reports; one high
      and one low risk result. Reports were reviewed for content and discussed at a
      meeting of laboratory providers and clinicians held at the ISPD 2016 conference
      in Berlin. RESULTS: Of the 122 laboratories that responded, 50 issued reports for
      NIPT and 43 of these submitted sample reports. Responses and reports were
      discussed by 72 attendees at the meeting. Consensus opinion was determined in
      several areas and used to develop best practice guidelines for reporting of NIPT
      results. CONCLUSIONS: Across Europe, there is considerable variation in reporting
      NIPT results. Here, we describe minimum best practice guidelines, which will be
      distributed to European laboratories, and reports audited in subsequent external
      quality assurance cycles. (c) 2017 The Authors. Prenatal Diagnosis published by
      John Wiley & Sons, Ltd.

PMID- 28497585
TI  - Disseminated CD8-positive, CD30-positive cutaneous lymphoproliferative eruption
      with overlapping features of mycosis fungoides and primary cutaneous anaplastic
      large cell lymphoma following remote solitary lesional presentation.
AB  - CD8-positive, CD30-positive cutaneous lymphoproliferative disorders constitute a
      rare subset of T-cell lymphoproliferative conditions, including variants of
      primary cutaneous anaplastic large cell lymphoma (ALCL), mycosis fungoides,
      lymphomatoid papulosis type D, cutaneous gamma-delta T-cell lymphoma and
      cutaneous peripheral T-cell lymphoma. These entities share overlapping clinical,
      histopathologic and immunophenotypic features, presenting both a clinical and
      pathological diagnostic challenge. Presented here is a 73-year-old man with a
      disseminated, indolent CD30+, CD8+ cutaneous lymphoproliferative disorder with
      overlapping clinical and histopathological features of both mycosis fungoides and
      primary cutaneous ALCL, as well as features of lymphomatoid papulosis. To our
      knowledge, this is the first case of a generalized CD8+, CD30+ eruption with
      features of both mycosis fungoides and primary cutaneous ALCL arising following
      an episode of solitary primary cutaneous CD8-positive ALCL.

PMID- 28497586
TI  - R-Ras deficiency does not affect papain-induced IgE production in mice.
AB  - INTRODUCTION: R-Ras GTPase has recently been implicated in the regulation of
      immune functions, particularly in dendritic cell (DC) maturation, immune synapse
      formation, and subsequent T cell responses. METHODS: Here, we investigated the
      role of R-Ras in allergen-induced immune response (type 2 immune response) in
      Rras deficient (R-Ras KO) and wild type (WT) mice. RESULTS: Initially, we found
      that the number of conventional DC's in the lymph nodes (LNs) was reduced in R
      Ras KO mice. The expression of co-stimulatory CD80 and CD86 molecules on these
      cells was also reduced on DC's from the R-Ras KO mice. However, there was no
      difference in papain-induced immune response between the R-Ras WT and KO as
      measured by serum IgE levels after the immunization. Interestingly, neither the
      DC number nor co-stimulatory molecule expression was different between WT and R
      Ras KO animals after the immunization. CONCLUSIONS: Taken together, despite
      having reduced number of conventional DC's in the R-Ras KO mice and low
      expression of CD80 on DC's, the R-Ras KO mice are capable of mounting papain
      induced IgE responses comparable to that of the WT mice. To our knowledge, this
      is the first report addressing potential differences in in vivo allergen
      responses regulated by the R-Ras GTPase.

PMID- 28497587
TI  - Office-based procedures for diagnosis and treatment of esophageal pathology.
AB  - BACKGROUND: Diagnostic and therapeutic office-based procedures under topical
      anesthesia are emerging in the daily practice of laryngologists and head and neck
      surgeons. Since the introduction of the transnasal esophagoscope, office-based
      procedures for the esophagus are increasingly performed. METHODS: We conducted a
      systematic review of literature on office-based procedures under topical
      anesthesia for the esophagus. RESULTS: Transnasal esophagoscopy is an extensively
      investigated office-based procedure. This procedure shows better patient
      tolerability and equivalent accuracy compared to conventional transoral
      esophagoscopy, as well as time and cost savings. Secondary tracheoesophageal
      puncture, esophageal dilatation, esophageal sphincter injection, and foreign body
      removal are less investigated, but show promising results. DISCUSSION: With the
      introduction of the transnasal esophagoscope, an increasing number of diagnostic
      and therapeutic office-based procedures for the esophagus are possible, with
      multiple advantages. Further investigation must prove the clinical feasibility
      and effectiveness of the therapeutic office-based procedures.

PMID- 28497588
TI  - Facilitating early diagnosis of lung cancer amongst primary care patients: The
      views of GPs.
AB  - Early diagnosis of lung cancer (LC) is a policy priority. However, symptoms are
      vague, associated with other morbidities, and frequently unrecognised by both
      patients and general practitioners (GPs). This qualitative study, part of a
      larger mixed methods study, explored GP views regarding the potential for early
      diagnosis of LC within primary care. Five focus group discussions (FGDs) were
      conducted with GPs (n = 16) at primary care practices (n = 5) across four
      counties in south England. FGDs were audio-recorded, transcribed verbatim and
      analysed using a framework approach. Four broad themes emerged: patients'
      reporting of symptoms; GP response to symptoms; investigating LC, and; potential
      initiatives for early diagnosis. GPs reported they often required high levels of
      suspicion to refer patients on to specialist respiratory consultations, and
      concerns of 'system overload' were prevalent. Greater access to more sensitive
      diagnostic investigations such as computed tomography, was argued for by some,
      particularly for symptomatic patients with negative chest X-rays. GPs challenged
      current approaches to promoting earlier diagnosis through national symptom
      awareness campaigns, arguing instead that interventions targeted at high-risk
      individuals might be more effective without burdening services already under
      pressure. Further work is needed to identify primary care patients who might most
      benefit from such targeted interventions.

PMID- 28497589
TI  - Asia-Pacific Colorectal Screening score: A useful tool to stratify risk for
      colorectal advanced neoplasms in Vietnamese patients with irritable bowel
      syndrome.
AB  - BACKGROUND AND AIM: The Asia-Pacific Colorectal Screening (APCS) score has been
      validated in several populations but not yet in patients with irritable bowel
      syndrome (IBS). The aim of this study was to assess the performance of APCS score
      in stratifying risk of colorectal advanced neoplasms (CAN) in Vietnamese IBS
      patients. METHODS: Consecutive patients who fulfilled IBS diagnosis criteria
      according to the Rome III were prospectively enrolled and underwent colonoscopy.
      APCS score for each patient was calculated by summing the points attributed by
      risk factors. Three tiers of risk were defined: 0-1 "average risk" (AR); 2-3
      "moderate risk" (MR); and 4-7 "high risk" (HR). Logistic regression analysis was
      performed to assess the relative risk of CAN in HR group and MR group compared
      with AR group. RESULTS: There were 404 patients with excellent bowel preparation
      and complete colonoscopy. The mean age was 48.8 +/- 11.2 years and male : female
      ratio was 1.2:1. Twenty-eight patients (6.9%) were diagnosed with CAN: 19 (4.7%)
      advanced adenoma and 9 (2.2%) invasive colorectal cancer. Patients in the MR and
      HR tiers had 5.6-fold (95% confidence interval 1.2 to 24.7, P = 0.012) and 12.1
      fold (95% confidence interval 2.6 to 56.2, P < 0.001) increased rates of CAN
      compared with those in the AR tier, respectively. Three out of 9 patients with
      invasive colorectal cancer had no alarm features but had high sum APCS score (2
      in MR tier and 1 in HR tier). CONCLUSION: The APCS score is useful to identify
      IBS patients with high risk of CAN for colonoscopy priority.

PMID- 28497590
TI  - Multimodality characterization of a noncommunicating congenital duodenal
      duplication cyst causing pyloric outflow obstruction in a young dog.
AB  - A 10-month-old German Shepherd Dog presented for evaluation of intermittent
      vomiting. Abdominal radiographs revealed a marked right cranial mass effect.
      Initial differentials included abscess/cyst or less likely neoplasia from
      undetermined origin. On abdominal ultrasound the mass appeared cystic and thin
      walled. Computed tomography revealed a large cystic lesion originating from the
      pyloroduodenal junction causing pyloric outflow obstruction. A noncommunicating
      duodenal duplication cyst was found on exploratory laparotomy and further
      confirmed with histopathology and immunohistochemistry. Enteric duplication cyst
      should be considered as a differential in young dogs with gastrointestinal signs
      and a cystic abdominal mass detected with different imaging modalities.

PMID- 28497591
TI  - Hypophosphatemia after nontraumatic intracranial hemorrhage.
AB  - BACKGROUND: The aim of this study was to assess the incidence and contributing
      factors of hypophosphatemia and the association with poor long-term outcome after
      nontraumatic intracranial hemorrhage. METHODS: This was a prospective,
      observational study of patients with nontraumatic intracranial hemorrhage (i.e.,
      aneurysmal or perimesencephalic subarachnoid hemorrhage, or spontaneous
      intracerebral or intraventricular hemorrhage) treated in the intensive care unit
      (ICU) at our university hospital. Plasma phosphate concentrations were measured
      serially in 2-day sections during the 6 day study period. The ICU mortality was
      recorded, 3-month and 1-year outcomes were assessed using the Glasgow Outcome
      Scale. RESULTS: One hundred patients were enrolled. The frequency of
      hypophosphatemia (Pi <= 0.65 mmol/l) was 70%. Chronic hypertension, acute
      hydrocephalus, and diffuse brain edema were more common in patients with
      hypophosphatemia compared with normophosphatemics (44% vs. 21%, P = 0.021; 59%
      vs. 33%, P = 0.021; and 43% vs. 13%, P = 0.004, respectively). Hypophosphatemic
      patients had higher maximum SOFA scores [10 (7-11) vs. 7.5 (5.75-10), P = 0.024].
      Initial phosphate concentration correlated inversely with APACHE II score on
      admission (rho = -0.304, P = 0.002) and SOFA score on the first ICU day (rho = 
      0.269, P = 0.008). There was no difference in outcome between hypophosphatemic
      and normophosphatemic patients. In all five patients with severe hypophosphatemia
      (Pi < 0.32 mmol/l) the functional outcome was good. CONCLUSION: Hypophosphatemia
      was common in this patient population. The outcome was similar between
      hypophosphatemic and normophosphatemic patients. Chronic hypertension, acute
      hydrocephalus, diffuse brain edema and higher SOFA scores were more common in
      patients with hypophosphatemia.

PMID- 28497592
TI  - Hypoglycaemia seriousness and weight gain as determinants of cardiovascular
      disease outcomes among sulfonylurea users.
AB  - AIMS: Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and
      weight gain, and thus might counteract the benefits of intensive glucose control.
      We quantify the association of cardiovascular disease (CVD) outcomes with
      hypoglycaemia and weight gain among patients with type 2 diabetes treated with
      sulfonylureas. MATERIALS AND METHODS: This cohort study included patients from
      January 2009 through December 2014 who were selected from within a deidentified
      nationwide electronic health records repository, including multiple provider
      networks and electronic medical records systems. Hypoglycaemia measures from
      structured data fields and free text clinical notes were categorized as serious
      or non-serious. Covariate adjusted Poisson regression analysis was used to assess
      the association between frequency of hypoglycaemia (by severity), or magnitude of
      weight change, and incidence of acute myocardial infarction (AMI), congestive
      heart failure (CHF) and stroke. RESULTS: Among 143 635 eligible patients, we
      observed 5669 cases of AMI, 14 109 incident cases of CHF and 7017 cases of
      stroke. Overall incidence rates were 1.53, 4.26 and 1.92 per 100 person-years for
      AMI, CHF and stroke, respectively. The associations between overall hypoglycaemia
      and each of the CVD outcomes were positive, with stronger associations observed
      for serious hypoglycaemia and attenuated or null associations observed for non
      serious hypoglycaemia. Weight change exhibited a U-shaped association with
      increased risks associated with both weight loss and weight gain relative to
      stable weight. CONCLUSIONS: This study provides evidence of increased CVD risk
      associated with hypoglycaemia, especially with serious hypoglycaemia events.
      While associations were attenuated with non-serious hypoglycaemia, the results
      were suggestive of a potential increased risk.

PMID- 28497595
TI  - Criteria for conceptualizing behavioural addiction should be informed by the
      underlying behavioural mechanism.

PMID- 28497594
TI  - The impact of regulatory action on the co-prescribing of renin-angiotensin system
      blockers in UK primary care.
AB  - PURPOSE: The aim of this study was to assess the impact of regulatory action
      taken in June 2014 on the co-prescribing of renin-angiotensin system (RAS)
      blockers in UK primary care. METHODS: RAS blocker prescriptions, issued between
      01/01/2009-30/06/2015, were extracted from the Clinical Practice Research
      Datalink to estimate the quarterly prevalence (number of patients with at least
      one co-prescription) and incidence (number of patients first receiving a RAS
      blocker co-prescription) of co-prescribing. Two different RAS blockers prescribed
      on the same day constituted a co-prescription. RESULTS: A total of 880 364
      patients were prescribed a single RAS blocker during the study period. Prevalence
      of co-prescribing increased from 4812 patients per million person-years in Q1
      2009 to 4865 in Q1 2010. A reduction then occurred decreasing to 2901 patients
      per million person-years in Q2 2014 when the EU review concluded and continued to
      decrease thereafter despite a continued increase in the prevalence of prescribing
      of a single RAS blocker. Incidence of new co-prescribing decreased from 454
      patients per million person-years in Q1 2009 to 159 in Q2 2014, but remained
      relatively constant at ~119 patients per million person-years on average after
      the EU review concluded. A total of 96% of co-prescriptions were for an ACE
      inhibitor + ARB, and 4% accounted for an ACE inhibitor or ARB + renin inhibitor.
      CONCLUSIONS: Recently, there has been a decrease in the prevalence and incidence
      of RAS blocker co-prescribing. Reassuringly, overall co-prescribing reduced in
      line with recommendations, although there was a decreasing trend prior to this
      likely due in part to prior publication of the data used in the EU review. (c)
      2017 Crown copyright. Pharmacoepidemiology and Drug Safety (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28497593
TI  - Polymorphism of receptor-type tyrosine-protein phosphatase delta gene in the
      development of non-alcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: Some single-nucleotide polymorphisms (SNPs) are associated
      with the development of non-alcoholic fatty liver disease (NAFLD). As one of the
      genetic factors, PNPLA3 rs738409 (I148M) is important to associate with
      pathogenesis of NAFLD. Because other SNPs remain unclear in Japan, we performed a
      high-throughput sequencing that targeted more than 1000 genes to identify a novel
      genetic variant in Japanese patients with NAFLD. METHODS: The present study in 36
      NAFLD patients and 27 healthy volunteers was performed. A high-throughput
      sequencer was used to detect the gene variations. Candidate genes were validated
      by TaqMan SNP genotyping assay in 53 NAFLD patients and 41 healthy volunteers. To
      investigate the function of candidate gene, we performed biochemical analyses in
      cultured hepatocytes and liver tissues. RESULTS: EXO1 rs1047840, PTPRD
      rs35929428, IFNAR2 rs2229207, CPOX rs1131857, IL23R rs1884444, IL10RA rs2228055,
      and FAM3B rs111988437 were identified as candidate genetic variants, and PTPRD
      rs35929428 was only extracted as a SNP predicting to cause protein dysfunction.
      In validation analysis, PTPRD rs35929428 associated with the development of NAFLD
      (P = 0.015, odds ratio = 5.00, 95% confidence interval: 1.33-18.70). In addition,
      PTPRD rs35929428 was associated with Fib-4 index and with hepatic fat droplets.
      Biochemical analyses indicated that PTPRD rs35929428 promoted dephosphorylation
      of tyrosine 705 signal transducer and activator of transcription 3 (Tyr 705) in
      hepatocytes. CONCLUSION: PTPRD rs35929428 was a novel SNP in patients with NAFLD.
      Through exacerbation of the dephosphorylation of signal transducer and activator
      of transcription 3 (Tyr 705) in hepatocytes, PTPRD rs35929428 might play a role
      in hepatic lipid accumulation and fibrosis, followed by the development of NAFLD.

PMID- 28497596
TI  - Development of immunochromatographic colloidal gold test strip for rapid
      detection of Haemophilus influenzae in clinical specimens.
AB  - AIMS: A simple and fast test strip for simultaneous detection of Haemophilus
      influenzae, based on the theory of colloidal gold immunochromatography was
      developed. METHODS AND RESULTS: In this study, monodispersional colloidal gold
      and gold-labelled polyclonal antibody (AbP6Line) specific to the linear antigenic
      determinant OMP6 of H. influenzae were prepared, and identified by UV-visible
      spectroscopy (200-700 nm) and transmission electron microscopy. The test strip
      was assembled on a plastic backing containing a sample pad, a conjugate pad, an
      absorbent pad and a nitrocellulose membrane, on which test and control lines were
      stuck. The strip showed us specific recognization of H. influenzae and did not
      identify other common respiratory pathogens such as Streptococcus pneumoniae,
      Mycoplasma pneumoniae, Moraxella catarrhalis and Legionella pneumophila. It was
      shown that the detection limit of the test strip was as low as 1 * 106 CFU per ml
      and the whole process can be completed within 10 min. The strips could be stored
      at 4 degrees C for at least 6 months without losing sensitivity or specificity.
      CONCLUSIONS: The test strip was specific, simple and convenient for rapid
      detection of H. influenzae presenting good stability and reproducibility.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The test strip provides a simple,
      convenient and specific tool for the on-site surveillance and diagnosis of H.
      influenzae infection in clinical samples.

PMID- 28497597
TI  - Constructing a theory of the triple typology: Some (second) thoughts on
      nomothetic and idiographic approaches to personality.
AB  - Our fundamental scientific task is to convert observations of particular persons
      behaving in particular ways in particular situations into assertions that certain
      kinds of persons will behave in certain kinds of ways in certain kinds of
      situations, that is, to construct triple typologies or equivalence classes-of
      persons, of behaviors, and of situations-and to fashion theories of personality
      that relate these equivalence classes to one another. It is argued that the
      different approaches to the study of personality are distinguished from one
      another not by whether they are idiographic or nomothetic but by the strategies
      they employ for constructing-or ignoring-each of these three types of equivalence
      classes. The likely attributes of a successful interactional theory of
      personality-one that would embrace the entire triple typology-are proposed and
      discussed.

PMID- 28497598
TI  - Aggregation and beyond: Some basic issues on the prediction of behavior.
AB  - Failure to appreciate the role that aggregation plays in increasing reliability
      and validity and in establishing the range of generalization of findings has
      resulted in misunderstandings about the stability of behavior across time and
      situations, and in the conduct of experiments that produce results that tend to
      be neither generalizable nor replicable. Appropriate aggregation can reduce error
      variance associated with the unrepresentativeness of individual stimuli,
      situations, occasions, judges, items of behavior, and subjects. Inappropriate
      aggregation can result not only in a loss of information but also in a reduction
      in reliability as well as validity. Different approaches to prediction with
      single items of behavior are discussed, and it is concluded that single items
      tend to be too unreliable and too narrow in scope to measure broad dispositions
      such as traits. A major emphasis is that behavior is often so highly
      situationally specific that unless this is taken into account by procedures such
      as aggregation over situations and/or occasions, or by the investigation of
      events that are so highly ego-involving that experimental effects dominate
      situation-ally unique effects, results will tend to be unreplicable or
      ungeneralizable, no matter what their level of statistical significance.

PMID- 28497599
TI  - Studies in intuitive personology from an idiothetic point of view: Implications
      for personality theory.
AB  - Following Lamiell's (1981) critique of the individual differences approach to the
      scientific study of personality, questions have arisen concerning (a) the nature
      of the empirical research to which the "idiotheric" framework he proposed as an
      alternative has thus far led, and (b) the wider theoretical implications of that
      research. The present article seeks to address these questions within the medium
      of research on the nature of the reasoning process by which lay persons formulate
      and express subjective personality impressions. It is argued that the findings of
      this research offer strong empirical support for a conception of the intuitive
      personologist as a dialectician. Among other things, the discussion of these
      findings focuses on their implications for a humanistic conception of the
      relation between cognition and behavior, and thus of personality more broadly
      defined.

PMID- 28497600
TI  - The "consistency" controversy and the accuracy of personality judgments.
AB  - Areas of clear and acknowledged disagreement in the personality literature's
      "consistency controversy" are surprisingly difficult to pin down. The present
      essay suggests that one basic and real disagreement nowadays is the admissability
      of subjective judgments of personality as data: Personologists are willing to use
      them, and situationists are not. Situationists generally regard judgments as so
      influenced by error as to be essentially unusable, and instead prefer direct
      measurements of specific behaviors. The relative uses and limitations of global
      judgments and specific measures are considered. It is concluded that any position
      that judgments reflect "nothing but" error is untenable. It is further concluded
      that each sort of data has distinct uses and limitations, provides a check on the
      other, and is indispensable.

PMID- 28497601
TI  - Self-knowledge: An expanded view.
AB  - This paper argues for a more extensive study of self-knowledge. From the
      cognitive perspective, self-knowedge is a critical component of personality.
      Until quite recently, however, the study of self-knowledge has been narrowly
      conceived, focusing primarily on how individuals describe their roles and
      characteristic behaviors. Yet individuals also have knowledge about their
      preferences and values, their goals and motives, and their rules and strategies
      for regulating behavior. These dynamic aspects of self-knowledge are significant
      because they can be importantly revealing of future behavior. The content and
      organization of self-knowledge is important first because it indicates which
      domains of behavior are regarded as the most self-relevant. It is in these
      domains that the strongest links between personality and behavior will be
      observed. Second, self-knowledge cognitively represents desired and undesired
      states for the self, as well as specific ideas about how to realize or avoid
      these states. It thus indicates the likely course of behavior in self-relevant
      domains. A number of recent research efforts can be intepreted as explorations of
      self-knowledge. These are briefly reviewed and integrated to provide a general
      outline for an expanded view of self-knowledge.

PMID- 28497602
TI  - Interactionism, idiographics, and the social psychological invasion of
      personality.
AB  - The present paper discusses three recent developments in the field of
      Personality: (1) an infusion of social psychologists, (2) a proliferation of
      interactionist models, (3) the development of methodological strategies combining
      nomothetic and idiographic approaches. Advantages and disadvantages of these
      developments are discussed, and three problems associated with them are
      addressed: (1) an overemphasis on phenomenology, (2) an overemphasis on
      idiosyncracy, and (3) an unsatisfactory level of theory development. It is
      concluded that the present developments have had a stimulating effect on the
      field but they need to be integrated with the traditional personological goals
      of: (1) developing taxonomy of individuals (as well as a taxonomy of
      interactions) and (2) developing a more satisfactory theory of the whole organism
      within which to embed our minitheories. We recommend that such a theory attempt
      to incorporate the insights of the social learning and social cognition
      approaches with the recent and exciting developments in evolutionary theory.

PMID- 28497603
TI  - Self-attention and self-report: The "veridicality" hypothesis.
AB  - Wicker (1969) summarized the state of the art in the area of attitude/behavior
      consistency by suggesting that attitude measures are often only slightly related
      to overt behaviors. Since that time literally hundreds of studies have been
      conducted dealing with the question of how the predictive validity of self
      assessment can be improved-above the 30 figure that Wicker suggested represents
      the typical upper limit of correlations between self-reported attitudes and
      behavior. This article deals with perhaps one of the simplest factors that does
      appear to be related to accurate self-assessment: internal focus of attention.
      Research in the area of self-awareness theory is discussed, leading to the
      conclusion that assessments of various aspects of the self, including attitudes,
      cognitions, and affective and somatic states, usually are more accurate when they
      are made by a respondent whose attention is self-directed. By the same token,
      overt behavior also tends to be more consistent with previously expressed
      attitudes when it occurs under conditions conducive to self-focus. In discussing
      this research, it is suggested that self-awareness promotes accuracy in two ways:
      (a) It focuses the respondent's attention more carefully on those aspects of the
      self made relevant by the instrument and (b) it increases the person's motivation
      to report accurately on those self-dimensions. It is also suggested, however,
      that this latter factor can sometimes work against consistency. In this regard, a
      variety of situations are discussed in which motives that may conflict with the
      desire to report accurately, such as ego-protectiveness, are also enhanced by
      self-focused attention. Finally, a number of empirical questions are presented as
      guidelines for future research.

PMID- 28497604
TI  - Personality and prediction: An introduction.

PMID- 28497605
TI  - Parallals between attitudes and traits as predictors of behavior.
AB  - Both attitudes and traits have served as within-person constructs intended to
      permit the prediction of later behavior. Despite this similarity, research in the
      two domains has tended to progress in a relatively independent fashion. A number
      of parallels between the attitude and trait literature are noted with regard to
      definitions of the constructs and their utility as predictors of behavior.
      Parallels with respect to the identification of variables that moderate the
      attitude-behavior and trait-behavior relation are also discussed, as are
      similarities in the potential processes by which attitudes and traits guide
      behavior. It is concluded that the parallels are so extensive that research in
      each domain would benefit from an increased exchange of theory, methods, and
      findings.

PMID- 28497606
TI  - Idiographic goals and methods in the study of lives.
AB  - The goal of psychology is "the development of generalizations of ever increasing
      scope, so that greater and greater varieties of phenomena may be explained by
      them, larger and larger numbers of questions answered by them, and broader and
      broader reaching predictions and decisions based upon them." Leon Levy (1970, p.
      5) "To generalize is to be an idiot." William Blake ABSTRACT: Learning what is
      true of persons-in-general and of groups of people often has severe limitations
      in enabling us to understand and predict the behavior of individuals. There are
      many important problems in describing, explaining, making predictions about, and
      intentionally changing the course of experience in individual lives that cannot
      be adequately addressed without the use of idiographic methods. The purposes of
      this paper are to contribute to a conceptual clarification of the idiographic
      approach and its place within psychology, to review and respond to a number of
      common criticisms of the idiographic approach, and finally, to update and extend
      Allport's survey of available idiographic methods.

PMID- 28497607
TI  - Alternatives in the pursuit of the predictability and consistency of persons:
      Stable data that yield unstable interpretations.
AB  - After a review of the historical roots of current issues in personality
      psychology, useful sources for prediction are summarized and some current
      convergences in the search for coherence are identified. The value of people as
      expert assessors is reiterated and the stability, consistency, and predictability
      of behavior are distinguished as multiple issues. In the pursuit of consistency
      in social behavior, two major routes emerge. One route aggregates data across
      situations and response modes, thereby reducing the variance from those sources,
      and identifies the resulting stable individual differences. The second route
      assesses consistency from situation to situation, searches for its psychological
      bases, and focuses on the discriminativeness of behavior as well as its
      coherence. Each route serves different purposes and has value for those different
      goals; neither one preempts the other. Years of research on the consistency of
      social behavior from situation to situation have yielded stable results that
      sometimes are used to reach opposite interpretations. But these puzzling
      differences reflect the two contrasting routes and goals in the search for
      consistency, not instabilities in the data nor a neglect of psychometric
      principles. Theory-guided predictions within particular empirical contexts are
      needed now to explore more deeply when and how either discriminative or more
      generalized patterns of coherence occur, and to illuminate their psychological
      bases with increasing precision.

PMID- 28497608
TI  - The influence of individuals on situations: Implications for understanding the
      links between personality and social behavior.
AB  - In an analysis of the nature and origins of predictability in social behavior,
      two propositions are considered: (1) There exist categories of individuals whose
      social behavior is readily predictable from measures of personal attributes such
      as attitudes, traits, and dispositions as well as categories of individuals whose
      social behavior is readily predictable from situational and interpersonal
      specifications of behavioral appropriateness; (2) underlying these differences in
      predictability are systematic choices to enter and to spend time in social
      settings and interpersonal contexts that promote and facilitate one or other of
      these characteristic behavioral orientations. The implications of these
      propositions for the study of personality and social behavior are considered in
      the specific case of the psychological construct of self-monitoring and in the
      general case of understanding the reciprocal influences of individuals and their
      social worlds.

PMID- 28497609
TI  - Implicit psychophysiology: Effects of common beliefs and idiosyncratic
      physiological responses symptom reporting.
AB  - Every individual exhibits unique perceptual, behavioral, and physiological
      responses within and across a variety of settings. Despite the idiosyncratic
      nature of responses, we seek to establish theories that generalize across a large
      number of individuals. A strict idiographic method intensively examines the
      response patterns of a small number of individuals, whereas a nomothetic approach
      focuses on common responses across a large number of individuals. In the present
      investigation, we seek to learn how individuals perceive and report physical
      symptoms and sensations. We offer a methodology that capitalizes on the unique
      physiological responses of individuals but, at the same time, assumes that the
      underlying perceptual processes relevant to symptom reporting are comparable
      across individuals. Our approach, then, is both idiographic and nomothetic. As
      will be discussed, this integrative approach has the potential to be applied to a
      multitude of behaviors and processes that are of interest to social and
      personality psychologists.

PMID- 28497610
TI  - Epilepsia partialis continua after an anterior circulation ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: Although cerebrovascular disorders are the main cause of
      epilepsia partialis continua (EPC) in adulthood, the frequency of EPC after
      stroke is unknown. The aim was to prospectively ascertain its frequency 1 year
      after an ischaemic stroke. METHODS: This was a prospective study of consecutive
      acute anterior circulation ischaemic stroke patients, previously independent,
      with an admission National Institutes of Health Stroke Scale score >=4, an acute
      ischaemic lesion on imaging and no previous epileptic seizures. During admission
      patients received standardized diagnostic and medical care and were submitted to
      a neurophysiological evaluation protocol. One year after stroke, patients were re
      evaluated by an epilepsy expert neurologist and performed a video
      electroencephalogram with electromyography co-registration whenever myoclonus was
      observed during neurological examination for jerk-locked back averaging analysis
      (JLBA). EPC was defined as continuously repeated fragments of epileptic seizures,
      with preserved consciousness, lasting at least 1 h, and representing locally
      restricted epileptic activity. RESULTS: In all, 151 acute anterior circulation
      stroke patients were consecutively included and prospectively evaluated, but 23
      died in the first year. One year after stroke, from 127 patients alive, 117
      (92.1%) underwent clinical and neurophysiological evaluation. In two (1.7%)
      patients, EPC diagnosis was made both by clinical and electroencephalographic
      criteria, namely JLBA. Both patients had a history of remote symptomatic seizures
      and one of them acute symptomatic seizures and non-convulsive status epilepticus
      criteria during the first 7 days after stroke. CONCLUSIONS: Despite its low
      frequency, the high stroke incidence makes post-stroke EPC relevant. This study
      draws attention to this recognizable condition with therapeutic and eventually
      prognostic implications.

PMID- 28497611
TI  - Co-inheritance of alpha0 -thalassemia elevates Hb A2 level in homozygous Hb E:
      Diagnostic implications.
AB  - INTRODUCTION: Differentiation of homozygous hemoglobin (Hb) E with and without
      alpha0 -thalassemia is subtle on routine hematological ground. We examined in a
      large cohort of homozygous Hb E if the level of Hb A2 is helpful. METHODS: A
      total of 592 subjects with homozygous Hb E were recruited from ongoing
      thalassemia screening program. Additionally, five couples at risk of having
      fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also
      investigated. Hb analysis was performed using capillary electrophoresis system.
      Globin genotypes were defined by DNA analysis. RESULTS: Subjects were classified
      into four groups including pure homozygous Hb E (n=532), homozygous Hb E/alpha0 
      thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's
      disease (n=4). The levels of Hb A2 were found, respectively, to be 4.97+/-0.69,
      6.64+/-1.02, 4.86+/-0.87, and 7.60+/-1.04%. Among five couples at risk, alpha0 
      thalassemia was identified in three subjects with Hb A2 >6.0%. CONCLUSIONS:
      Increased Hb A2 level is a useful marker for differentiation of homozygous Hb E
      with and without alpha0 -thalassemia. This should lead to a significant reduction
      in number of referral cases of homozygous Hb E for molecular testing of alpha0 
      thalassemia in routine practice.

PMID- 28497612
TI  - Accurate assessment of alpha-gal syndrome using cetuximab and bovine
      thyroglobulin-specific IgE.
AB  - SCOPE: IgE against galactose-alpha-1,3-galactose (alpha-Gal) causes alpha-gal
      syndrome. Bovine thyroglobulin (BTG) and cetuximab share this epitope. We aimed
      to determine the utility of specific IgE (sIgE) against cetuximab as compared to
      BTG for diagnosing alpha-gal syndrome. METHODS AND RESULTS: Twelve patients with
      alpha-gal syndrome, 11 patients with immediate beef or pork allergy, 18
      asymptomatic individuals with meat sensitization, and 10 non-atopic subjects were
      enrolled. We checked the levels of sIgE against BTG and cetuximab using the
      streptavidin CAP assay. Additionally, IgE reactivity to BTG and cetuximab was
      assessed by immunoblotting. All alpha-gal syndrome patients had a high
      concentration of sIgE against BTG, and cetuximab. In contrast to alpha-gal
      syndrome, patients with immediate allergic reactions to meat consumption and
      those with asymptomatic sensitization had significantly lower concentration of
      BTG and cetuximab sIgE, and a high prevalence of sIgE against bovine or porcine
      serum albumin. Although the concentration of sIgE against alpha-gal was lower in
      individuals with asymptomatic sensitization, IgE immunoblotting showed the
      presence of sIgE against alpha-Gal in this group. CONCLUSION: Differentiation of
      alpha-gal syndrome from patients with immediate allergy to meat consumption or
      asymptomatic sensitization requires quantification of cetuximab- or BTG-induced
      sIgE via detection of IgE for alpha-gal.

PMID- 28497613
TI  - Effectiveness of a nurse-led preadmission intervention for parents of children
      with profound multiple disabilities undergoing hip-joint surgery: A quasi
      experimental pilot study.
AB  - PURPOSE: The aim of this study was to assess the effectiveness of a family
      centered care (FCC) intervention provided by an advanced practice nurse (APN) for
      parents of children with profound disabilities undergoing surgery. DESIGN AND
      METHODS: In a quasi-experimental design, we used the MPOC-20 to assess
      satisfaction with FCC and interviews to identify potential mechanisms for
      improving satisfaction. RESULTS: There was a positive effect on the MPOC-20
      domain "general information," albeit with a small effect size (Cohen's d = 0.35).
      The interviewed parents expected additional support. PRACTICE IMPLICATIONS:
      Emphasis should be placed on providing comprehensive care coordination by an
      experienced APN. Shared care management is crucial in improving FCC.

PMID- 28497615
TI  - Quantification of rat supraglottic laryngeal sensation threshold.
AB  - OBJECTIVE: Laryngeal adductor response (LAR) to air puff is used as a reliable
      method in evaluating sensation thresholds (ST) in human laryngeal sensory
      disorders. This method has been difficult to perform in small subjects such as
      rodents. The aims of this study were to 1) evaluate ST to air puff under
      binocular microlaryngoscopy in rats to evaluate laryngeal sensory disorders, 2)
      determine sensory thresholds at varying target locations, and 3) determine the
      ideal depth of anesthesia. STUDY DESIGN: Animal study. METHODS: Rats were induced
      with ketamine/xylazine. The level of anesthesia was monitored by spontaneous
      glottic closure and corneal reflex testing. Air puffs were delivered to the
      epiglottis, arytenoid, and piriform sinus at varied pressures with pulse time
      kept constant. Sensation thresholds were determined by direct visualization of
      the larynx using a binocular microscope. Topical lidocaine was then applied to
      the larynx and ST was determined. Trials were repeated in a small subset of
      animals. RESULTS: Twenty-six trials were performed in 14 rats. Mean STs were 39
      +/- 9.7 mm Hg at the epiglottis, 48.8 +/- 10.5 at the arytenoid, and not
      detectable at the pyriform sinus. Repeated trials demonstrated consistent
      results. Lidocaine effectively ablated the LAR in each trial. The LAR was
      difficult to induce while corneal reflex was absent and was difficult to
      distinguish from spontaneous glottic closures while under lighter sedation.
      CONCLUSION: Air pulse stimulation in rats is a simple, reliable, and effective
      way to determine laryngopharyngeal STs in rats and can be used as an efficient
      and affordable method for experimentation involving laryngeal sensory disorders.
      LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E265-E269, 2017.

PMID- 28497614
TI  - Broad Th2 neutralization and anti-inflammatory action of pentosan polysulfate
      sodium in experimental allergic rhinitis.
AB  - BACKGROUND: Th2 cytokines like interleukin-4, -5, and -13 are regarded as
      important drivers of the immunopathology underlying allergic rhinitis (AR) and
      asthma. The present study explores the capacity of pentosan polysulfate sodium
      (PPS), a semi-synthetic heparin-like macromolecular carbohydrate, to bind Th2
      cytokines and exert biological neutralization in vitro, as well as anti
      inflammatory actions in vivo. METHODOLOGY: The capacity of PPS to bind
      recombinant Th2 cytokines was tested with surface plasmon resonance (SPR)
      technology and biological Th2 neutralization was assessed by Th2-dependent
      proliferation assays. The in vivo anti-inflammatory action of PPS was studied
      using a validated Guinea-pig model of AR. RESULTS: Binding studies revealed a
      strong and specific binding of PPS to IL-4, IL-5, and IL-13 with IC values
      suggesting as stronger cytokine binding than for heparin. Cytokine binding
      translated to a biological neutralization as PPS dose dependently inhibited Th2
      dependent cell proliferation. Topical administration of PPS 30 min prior to nasal
      allergen challenge of sensitized animals significantly reduced late phase plasma
      extravasation, luminal influx of eosinophils, neutrophils, and total lavage
      leukocytes. Similar, albeit not statistically secured, effects were found for
      tissue leukocytes and mucus hyper-secretion. The anti-inflammatory effects of PPS
      compared favorably with established topical nasal steroid treatment. CONCLUSION:
      This study points out PPS as a potent Th2 cytokine-binding molecule with
      biological neutralization capacity and broad anti-inflammatory effects in vivo.
      As such PPS fulfills the role as a potential candidate molecule for the treatment
      of AR and further studies of clinical efficacy seems highly warranted.

PMID- 28497616
TI  - CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small
      molecules.
AB  - Reading ligand structures into any simulation program is often nontrivial and
      time consuming, especially when the force field parameters and/or structure files
      of the corresponding molecules are not available. To address this problem, we
      have developed Ligand Reader & Modeler in CHARMM-GUI. Users can upload ligand
      structure information in various forms (using PDB ID, ligand ID, SMILES,
      MOL/MOL2/SDF file, or PDB/mmCIF file), and the uploaded structure is displayed on
      a sketchpad for verification and further modification. Based on the displayed
      structure, Ligand Reader & Modeler generates the ligand force field parameters
      and necessary structure files by searching for the ligand in the CHARMM force
      field library or using the CHARMM general force field (CGenFF). In addition,
      users can define chemical substitution sites and draw substituents in each site
      on the sketchpad to generate a set of combinatorial structure files and
      corresponding force field parameters for throughput or alchemical free energy
      simulations. Finally, the output from Ligand Reader & Modeler can be used in
      other CHARMM-GUI modules to build a protein-ligand simulation system for all
      supported simulation programs, such as CHARMM, NAMD, GROMACS, AMBER, GENESIS,
      LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Ligand Reader & Modeler is available
      as a functional module of CHARMM-GUI at http://www.charmm-gui.org/input/ligandrm.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28497617
TI  - Association of NPR3 polymorphism with risk of essential hypertension in a Chinese
      population.
AB  - WHAT IS KNOWN AND OBJECTIVE: Essential hypertension (EH) is a common disease
      exhibiting large individual difference in occurrence, development and treatment
      response. Genetic factors are implicated in the development and progression of
      EH. This study aimed to explore the association between NPR3 single nucleotide
      polymorphism rs2270915 (A/G, Asn521Asp) and the risk of EH in a Chinese Han
      population by a case-control study. METHODS: The study was a single-centre, case
      control trial, in which a total of 287 EH patients and 289 age- and sex-matched
      healthy controls were enrolled. The inclusion criteria were as follows: Han
      Chinese origin, male or female patients, systolic blood pressure (SBP) >=140 mm
      Hg and/or diastolic blood pressure (DBP) >=90 mm Hg. The healthy controls were
      subjects without histories of cardiovascular or cerebrovascular diseases. NPR3
      rs2270915 polymorphism was genotyped by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). In addition, primary human umbilical
      vein endothelial cells (HUVECs) were isolated from 19 fresh human umbilical cords
      and cultured. Atrial natriuretic peptide (ANP) concentration in cell medium was
      determined by enzyme-linked immunosorbent assay (ELISA). NPR3 mRNA expression was
      determined by real-time semi-quantitative PCR. RESULTS AND DISCUSSION: No
      significant difference in genotype distribution of NPR3 rs2270915 polymorphism
      was observed between cases and controls (P>.05). Patients carrying the rs2270915
      G allele showed decreased SBP, and the difference was marginal. As compared with
      cells carrying the rs2270915 AA genotype, those with the AG genotype showed
      significantly lower NPR3 mRNA expression levels (P<.05) and lower medium ANP
      concentration (P<.001). WHAT IS NEW AND CONCLUSION: This study suggested that
      NPR3 rs2270915 polymorphism was associated with decreased SBP level marginally in
      EH patients in a Chinese Han population, and the polymorphism may function
      through decreasing NPR3 mRNA expression and ANP level.

PMID- 28497618
TI  - Crocodilian perivitelline membrane-bound sperm detection.
AB  - Advanced reproductive technologies (ART's) are often employed with various taxa
      to enhance captive breeding programs and maintain genetic diversity.
      Perivitelline membrane-bound (PVM-bound) sperm detection has previously been
      demonstrated in avian and chelonian species as a useful technique for breeding
      management. In the absence of embryotic development within an egg, this technique
      can detect the presence of sperm trapped on the oocyte membrane confirming
      breeding, male reproductive status, and pair compatibility. PVM-bound sperm were
      successfully detected in three clutches of Cuban crocodile (Crocodylus rhombifer)
      eggs at the Smithsonian's National Zoological Park (NZP) for the first time in
      any crocodilian species. PVM-bound sperm were detected in fresh and incubated C.
      rhombifer eggs, as well as eggs that were developing (banded) and those that were
      not (not banded). The results of this study showed significant differences in
      average sperm densities per egg between clutches (p = 0.001). Additionally, there
      was not a significant difference within clutches between eggs that banded and
      those that did not band (Clutch A, p = 0.505; Clutch B, p = 0.665; Clutch C, p =
      0.266). The results of this study demonstrate the necessity to microscopically
      examine eggs that do not develop (do not band), to determine if sperm is present,
      which can help animal managers problem solve reproductive shortcomings. PVM-bound
      sperm detection could be a useful technique in assessing crocodilian breeding
      programs, as well as have potential uses in studies assessing sperm storage,
      artificial insemination, and artificial incubation.

PMID- 28497619
TI  - Change in over-refraction after scleral lens settling on average corneas.
AB  - PURPOSE: The purpose of this study was to determine the change in over
      refraction, if any, after a scleral lens settled on the eye for 6-8 h. METHODS:
      Sixteen patients of varying refractive errors and normal corneal curvatures
      (measured with PentacamTM Oculus) were fitted with trial Mini-Scleral Design
      (MSD) scleral lenses (15.8 mm diameter) in one eye. The sagittal depths of the
      scleral lenses were selected by adding 350 MUm to the corneal sagittal heights
      measured at a chord length of 15 mm with the VisanteTM optical coherence
      tomographer (OCT) anterior segment scans and picking the closest available trial
      lens in the set. Initial measurements were taken 30 min after lens insertion and
      included an auto-refraction, subjective refraction, and best sphere refraction
      over the contact lens. Visual acuities and VisanteTM OCT anterior segment scans
      were also taken. These measurements were repeated after 6-8 h of lens wear.
      RESULTS: Over the trial wearing period, the average change in the spherical
      component of the over-refraction was +0.06 D (S.D. 0.17) (p = 0.16). The average
      change in cylinder was +0.04 D (S.D. 0.19) (p = 0.33). The average absolute
      change in axis was 1.06 degrees  (S.D. 12.11) (p = 0.74). The average change in
      best sphere was +0.13 +/- 0.30 D (p = 0.12). There was no significant change in
      visual acuity with the best sphere over-refraction over the 6-8 h wearing period.
      There was a significant change in central corneal clearance over the wearing
      period of 83 MUm (S.D. 22) (p < 0.0001). CONCLUSION: Despite a significant change
      in the central corneal clearance due to thinning of the fluid reservoir as the
      scleral lens settled (an average decrease of 83 MUm after wearing the lenses for
      6-8 h), there was not a statistically significant change in the subjective over
      refraction (sphere, cylinder, and axis) or best sphere or visual acuity. This
      study has confirmed that there is no link between reduction in central corneal
      clearance and change in over-refraction for average corneas.

PMID- 28497620
TI  - Accelerated whole-heart MR angiography using a variable-density poisson-disc
      undersampling pattern and compressed sensing reconstruction.
AB  - PURPOSE: To accelerate whole-heart three-dimension MR angiography (MRA) by using
      a variable-density Poisson-disc undersampling pattern and a compressed sensing
      (CS) reconstruction algorithm, and compare the results with sensitivity encoding
      (SENSE). METHODS: For whole-heart MRA, a prospective variable-density Poisson
      disc k-space undersampling pattern was developed in which 1-2% of central part of
      k-space was fully sampled, and sampling in the remainder decreased exponentially
      toward the periphery. The undersampled data were then estimated using CS
      reconstruction. In patients, images using this sequence with an undersampling
      rate of ~6 were compared with those using a SENSE rate of 2 (n = 15) and a SENSE
      rate of 6 (n = 13). RESULTS: Compared with SENSE rate 2, CS rate 6 images had
      similar objective border sharpness, significantly lower subjective image quality
      scores at all four locations (all P < 0.01), and shorter scan times (P < 0.05).
      Compared with SENSE rate 6, CS rate 6 had similar objective border sharpness at
      all four locations, significantly better subjective image quality scores at three
      of four locations (all P < 0.01), and similar scan times (P = 0.24). CONCLUSION:
      Compared with SENSE with a comparable acceleration rate, a variable-density
      Poisson-disc undersampling pattern and CS reconstruction achieved better
      subjective image quality and similar border sharpness. Magn Reson Med 79:761-769,
      2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 28497621
TI  - Endomyocardial and pericardial aspergillosis in critically ill patients.
AB  - Invasive aspergillosis(IA) is a potentially lethal complication of Aspergillus
      infection affecting mainly immunocompromised hosts; however, during the last two
      decades its incidence was increasingly observed in critically ill immunocompetent
      patients. The objective of this study is to describe the clinical characteristics
      of histologically proven endomyocardial and pericardial invasion, in the context
      of IA, in critically ill patients. Eight critically ill patients with
      histopathological confirmation of endomyocardial/pericardial aspergillosis were
      evaluated. Risk factors, clinical and laboratory characteristics, treatment,
      histopathological characteristics and mortality were recorded. Signs and symptoms
      of cardiac dysfunction were not observed in any of the patients. Therapy was
      administered to six of them shortly after the first positive culture. The
      observed histopathological lesions included haemorrhagic lesions, small vessels
      with central thrombosis and surrounding consolidated tissue with necrosis.
      Voriconazole, caspofungin, lipid amphotericin B and itraconazole were the used
      antifungals. The mortality rate was high (87.5%). Endomyocardial and pericardial
      aspergillosis are devastating complications of invasive aspergillosis. Clinical
      suspicion is low making the diagnosis difficult, therefore histopathological
      examination of tissues are required. The mortality is high.

PMID- 28497622
TI  - Non-contrast-enhanced T1 -weighted MRI of myocardial radiofrequency ablation
      lesions.
AB  - PURPOSE: To demonstrate imaging of radiofrequency ablation lesions with non
      contrast-enhanced T1 -weighted (T1w) MRI. METHODS: Fifteen swine underwent left
      ventricular ablation followed by MRI using different preparations: endocardial or
      epicardial ablation of naive animal, or endocardial ablation of animal with
      myocardial infarction. Lesion imaging was performed using free-breathing, non
      contrast-enhanced, T1w sequence with long inversion time (TI). Also acquired were
      T1 maps and delayed contrast-enhanced (DCE) imaging. Hearts were excised for ex
      vivo imaging, and sliced for gross pathology and histology. RESULTS: All
      ablations were visibly enhanced in non-contrast-enhanced T1w imaging using TI =
      700 ms. T1w enhancement agreed with regions of necrosis in gross pathology and
      histology. Enhanced lesion cores were surrounded by dark bands containing
      contraction band necrosis, hematoma, and edema. In animals with myocardial
      infarction, chronic scar was hypointense in T1w, whereas acute ablations were
      enhanced, allowing discrimination between chronic scar and acute lesions, unlike
      DCE. Contrast was sufficient to create 3D volume renderings of lesions after
      minor postprocessing. CONCLUSIONS: Non-contrast-enhanced T1w imaging with long TI
      promises to be an effective method for visualizing necrosis within radiofrequency
      ablation lesions. Enhancement is more specific and stationary than that from DCE.
      The imaging can be repeated as needed, unlike DCE, and may be especially useful
      for assessing ablations during or after a procedure. Magn Reson Med 79:879-889,
      2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 28497623
TI  - Gangrene caused by topically applied home-prepared aconite liniment.

PMID- 28497624
TI  - Two new cases of severe allergic contact dermatitis caused by acetophenone azine.

PMID- 28497625
TI  - Systemic allergic dermatitis caused by diltiazem.

PMID- 28497626
TI  - Allergic contact dermatitis caused by cobalt in leather - clinical cases.

PMID- 28497628
TI  - Successful patch testing of a patient receiving anti-interleukin-17 therapy with
      secukinumab: a case report.

PMID- 28497627
TI  - Allergic contact stomatitis caused by neem leaves (Azadirachta indica).

PMID- 28497629
TI  - The attitude of patients with p-phenylenediamine or 2,5-toluenediamine contact
      allergy to hair dyeing.

PMID- 28497630
TI  - Acute generalized exanthematous pustulosis caused by an iodinated contrast
      radiocontrast medium for computed tomography arthrography of the knee.

PMID- 28497631
TI  - The European nickel regulation and changes since its introduction.

PMID- 28497632
TI  - Acute generalized exanthematous pustulosis (AGEP) induced by azithromycin.

PMID- 28497633
TI  - Allergic contact dermatitis caused by poly(hexamethylene) biguanide hydrochloride
      in contact lens care solutions.

PMID- 28497635
TI  - Contact allergy to reactive dyes in footwear.

PMID- 28497634
TI  - Allergic contact dermatitis caused by cetearyl isononanoate in a sunscreen
      product.

PMID- 28497636
TI  - Contact allergy to thioctic acid present in Hypromellose(r) eye drops.

PMID- 28497637
TI  - Successful use of rivaroxaban in inferior vena cava thrombosis provoked by
      multiple traumatic injuries and surgeries: A case report.
AB  - WHAT IS KNOWN AND OBJECTIVES: There is a lack of consensus regarding optimal
      anticoagulation regimen and duration for inferior vena cava (IVC) thrombus due to
      the paucity of clinical evidence. A case of IVC thrombus treated with 3 months of
      rivaroxaban therapy is reported. CASE DESCRIPTION: Fifty-two-year-old male
      Caucasian presented following a motorcycle accident, with multiple left rib
      fractures requiring emergent amputation surgeries. During the hospitalization, he
      developed IVC thrombosis and completed 3 months of rivaroxaban treatment without
      any complication. The Doppler images at 6-week, 3-month and 6-month follow-up
      appointments showed no IVC thrombosis. WHAT IS NEW AND CONCLUSION: This is the
      first case of IVC thrombosis successfully treated with rivaroxaban. Further case
      series and clinical studies are needed to guide the use of direct oral
      anticoagulants for IVC thrombosis.

PMID- 28497638
TI  - Bounding the causal effect of unemployment on mental health: Nonparametric
      evidence from four countries.
AB  - An important, yet unsettled, question in public health policy is the extent to
      which unemployment causally impacts mental health. The recent literature yields
      varying findings, which are likely due to differences in data, methods, samples,
      and institutional settings. Taking a more general approach, we provide comparable
      evidence for four countries with different institutional settings-Australia,
      Germany, the UK, and the United States-using a nonparametric bounds analysis.
      Relying on fairly weak and partially testable assumptions, our paper shows that
      unemployment has a significant negative effect on mental health in all countries.
      Our results rule out effects larger than a quarter of a standard deviation for
      Germany and half a standard deviation for the Anglo-Saxon countries. The effect
      is significant for both men and women and materialises already for short periods
      of unemployment. Public policy should hence focus on early prevention of mental
      health problems among the unemployed.

PMID- 28497639
TI  - Functionalization of P4 through Direct P-C Bond Formation.
AB  - Research on chlorine-free conversions of P4 into organophosphorus compounds
      (OPCs) has a long track record, but methods that allow desirable, direct P-C bond
      formations have only recently emerged. These include the use of metal organyls,
      carbenes, carboradicals, and photochemical approaches. The versatile product
      scope enables the preparation of both industrially relevant organophosphorus
      compounds, as well as a broad range of intriguing new compound classes. Herein we
      provide a concise overview of recent breakthroughs and outline the acquired
      fundamental insights to aid future developments.

PMID- 28497640
TI  - Polarizable crystals in apocrine sweat gland tumors: A series of 3 cases.
AB  - Polarizable calcium oxalate (CaOx) crystals have been well documented in breast
      biopsies, generally associated with benign apocrine metaplasia. In contrast,
      polarizable crystals are only rarely reported in skin adnexal neoplasms. We
      report 3 different cases of sweat gland tumors with polarizable crystals
      morphologically suggestive of CaOx: 1 apocrine hidrocystoma and 2 tubular
      apocrine adenomas. The histologic features were examined in 3 cases. Clinical
      presentation summary included 2 males and 1 female, ages 53 to 74 years, with
      lesions located on the left cheek, inferior vertex scalp and the left eyebrow.
      All 3 cases showed polarizable, geometric, plate-like and fractured, colorless
      crystals within the lumens of the neoplasm. Of note, these crystals were seen
      only on the toluidine blue-stained section of Case #1, but were not present on
      the corresponding permanent section. We hypothesize that polarizable crystals may
      be present in sweat gland neoplasms more often than previously documented, but
      that they may often dissolve with routine processing, accounting for their rare
      visibility. We highlight this rare finding, and suggest that it may be
      underreported. We only noted this finding in benign apocrine tumors; further
      investigation would be necessary to determine whether these crystals are also
      seen in other cutaneous adnexal neoplasms.

PMID- 28497641
TI  - Adult executive functioning inventory (ADEXI): Validity, reliability, and
      relations to ADHD.
AB  - This study examined the psychometric properties of the Adult Executive
      Functioning Inventory (ADEXI). This new executive functioning (EF) rating
      instrument has the advantage of being brief (14 items) and focusing specifically
      on working memory and inhibitory control. Results showed that scores on the ADEXI
      had high internal consistency and adequate test-retest reliability, but low
      concurrence between self-ratings and other ratings. High and statistically
      significant correlations were found between ADEXI scores and scores from another
      EF rating instrument, whereas the correlations between ADEXI scores and
      neuropsychological test scores were weak and often non-significant. Furthermore,
      with regard to discriminant validity, individuals with attention deficit
      hyperactivity disorder (ADHD) had significantly higher scores on both the
      inhibition and working memory subscales compared to clinical as well as non
      clinical controls. The results showed high specificity, but relatively low
      sensitivity, when discriminating between adults with ADHD and non-clinical
      controls. Conclusively, the ADEXI can be a valuable screening instrument for
      assessing deficits in working memory and inhibitory control. However, similarly
      to other EF ratings, the ADEXI should be used as a complement rather than as a
      replacement for neuropsychological tests, and the low interrater reliability
      suggests that ratings from multiple sources is preferable compared to relying
      solely on self-ratings.

PMID- 28497642
TI  - Estimating lifetime medical costs from censored claims data.
AB  - Claims databases consisting of routinely collected longitudinal records of
      medical expenditures are increasingly utilized for estimating expected medical
      costs of patients with a specific condition. Survival data of the patients of
      interest are usually highly censored, and observed expenditures are incomplete.
      In this study, we propose a survival-adjusted estimator for estimating mean
      lifetime costs, which integrates the product of the survival function and the
      mean cost function over the lifetime horizon. The survival function is estimated
      by a new algorithm of rolling extrapolation, aided by external information of age
      and sex-matched referents simulated from national vital statistics. The mean
      cost function is estimated by a weighted average of mean expenditures of patients
      in a number of months prior to their death, of which the number could be
      determined by observed costs in their final months, and the weights depend on
      extrapolated hazards. We evaluate the performance of the proposed approach in
      comparison with that of a popular method using simulated data under various
      scenarios and 2 cohorts of intracerebral hemorrhage and ischemic stroke patients
      with a maximum follow-up of 13 years and conclude that our new method estimates
      the mean lifetime costs more accurately.

PMID- 28497643
TI  - Three-dimensional ultrashort echo time MRI and Short T2 images generated from
      subtraction for determination of tumor burden in lung cancer: Preclinical
      investigation in transgenic mice.
AB  - PURPOSE: To investigate the potential of 3D ultrashort echo time MRI and short T2
      images generated by subtraction for determination of total tumor burden in lung
      cancer. METHODS: As an animal model of spontaneously developing non-small cell
      lung cancer, the K-rasLA1 transgenic mouse was used. Three-dimensional MR imaging
      was performed with radial k-space acquisition and echo times of 20 us and 1 ms.
      For investigation of the short T2 component in the recorded signal, subtraction
      images were generated from these data sets and used for consensus identification
      of tumors. Next, manual segmentation was performed on all MR images by two
      independent investigators. MRI data were compared with the results from
      histologic investigations and among the investigators. RESULTS: Tumor number and
      total tumor burden from imaging experiments correlated strongly with the results
      of histologic investigations. Intra- and interuser comparison showed highest
      correlations between the individual measurements for ultra-short TE MRI.
      CONCLUSIONS: Three-dimensional MRI protocols facilitate accurate tumor
      identification in mice harboring lung tumors. Ultrashort TE MRI is the superior
      imaging strategy when investigating lung tumors of miscellaneous size with 3D MR
      imaging strategies. Magn Reson Med 79:1052-1060, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 28497644
TI  - Cost of illness of non-alcoholic liver cirrhosis in Japan: A time trend analysis
      and future projections.
AB  - AIM: Liver cirrhosis is a preneoplastic condition to hepatocellular carcinoma
      that is an important worldwide public health concern, and its economic burden has
      been estimated in some countries. The objective of this study was to estimate and
      predict the cost of illness (COI) associated with non-alcoholic liver cirrhosis
      in Japan. METHODS: Using a COI method on available data from government
      statistics, we estimated the economic burden in 3-year intervals from 1996 to
      2014. We then predicted the COI in 3-year intervals from 2017 to 2029 using fixed
      and variable model estimations. With fixed model estimation, only the estimated
      future population was used as a variable. Variable model estimation considered
      the time trends of health-related indicators throughout the past 18 years.
      RESULTS: The estimated COI of non-alcoholic liver cirrhosis was Y208.1bn in 2014.
      The COI of non-alcoholic liver cirrhosis had a downward trend from 1996 to 2014.
      The predicted future COI of non-alcoholic liver cirrhosis was Y144.3-210.5bn,
      Y106.0-213.8bn, Y88.6-213.4bn, Y76.7-215.5bn, and Y66.4-214.3bn in 2017, 2020,
      2023, 2026, and 2029, respectively. CONCLUSIONS: The results of this study
      suggest that the COI of non-alcoholic liver cirrhosis in Japan has steadily
      decreased and will continue to decrease. Treatment of patients with hepatitis C
      virus infection with newly introduced technologies has high therapeutic
      effectiveness, which will affect the future prevalence of non-alcoholic liver
      cirrhosis. When interpreting the results of long-term estimation, it should be
      noted that the results of this study were based on present conditions.

PMID- 28497645
TI  - Peptic ulcer bleeding patients with Rockall scores >=6 are at risk of long-term
      ulcer rebleeding: A 3.5-year prospective longitudinal study.
AB  - BACKGROUND AND AIM: Patients with high Rockall scores have increased risk of
      rebleeding and mortality within 30 days after peptic ulcer bleeding, but long
      term outcomes deserve follow-up after cessation of proton pump inhibitors. The
      paper aimed to validate whether patients with high Rockall scores have more
      recurrent ulcer bleeding in a 3.5-year longitudinal cohort. METHODS: Between
      August 2011 and July 2014, 368 patients with peptic ulcer bleeding were
      prospectively enrolled after endoscopic hemostasis to receive proton pump
      inhibitors for at least 8 to 16 weeks. These subjects were categorized into
      either a Rockall scores >=6 group (n = 257) or a Rockall scores <6 group (n =
      111) and followed up until July of 2015 to assess recurrent ulcer bleeding.
      RESULTS: The proportion of patients with rebleeding during the 3.5-year follow-up
      was higher in patients with Rockall scores >=6 than in those with scores <6
      (10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients
      with Rockall scores >=6, activated partial thromboplastin time prolonged >=1.5
      fold (P = 0.045), American Society of Anesthesiologists physical status class
      >=III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent
      factors found to increase rebleeding risk. The cumulative rebleeding rate was
      higher in patients with Rockall scores >=6 with more than or equal to any two
      additional factors than in those with fewer than two additional factors (15.69
      vs. 7.63 per 100 person-year, P = 0.012, log-rank test). CONCLUSIONS: Patients
      with Rockall scores >=6 are at risk of long-term recurrent peptic ulcer bleeding.
      The risk can be independently increased by the presence of activated partial
      thromboplastin time prolonged >=1.5-fold, American Society of Anesthesiologists
      class >=III, and gastric ulcer in patients with Rockall scores >=6.

PMID- 28497646
TI  - Azole-resistant Aspergillus fumigatus in sawmills of Eastern France.
AB  - AIMS: Emergence of azole-resistant Aspergillus fumigatus complicates management
      of Aspergillus diseases. Currently, selection pressure caused by azole fungicide
      use in farming is strongly suspected of creating resistance. As sawmills also use
      azole fungicides, we investigated the presence of azole-resistant strains in this
      environment and studied the relationship between azole fungicide use and
      development of resistance. METHODS AND RESULTS: Air (n = 200) and substrate (n =
      600) samples were taken in 20 sawmills. Azole-resistant strains (Etest and EUCAST
      methods) were confirmed by sequencing the cyp51A gene and its promoters. Dosage
      of propiconazole and tebuconazole was performed by gas chromatography coupled
      with mass spectrometry. Twenty-four azole-resistant A. fumigatus strains were
      collected among 20 of the 600 substrate samples (3%). Eighty-three percent of
      theses strains had TR34 /L98H mutation. A significantly higher number of
      resistant strains was collected in sawmills using fungicide products made with
      propiconazole mixed with a high concentration of tebuconazole (P = 0.009). The
      presence of resistant strains was significantly linked to propiconazole
      quantities in substrates (P = 0.03). CONCLUSIONS: The outcome of azole-resistant
      A. fumigatus carrying TR34 /L98H mutation seems to greatly depend on the azole
      fungicide formulation and quantities of azole. These preliminary results are
      valuable to propose new approaches limiting the emergence of azole-resistant
      strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Azole resistance is an emerging
      problem in A. fumigatus and threatens clinical advances made possible by the use
      of azole antifungals in the treatment of Aspergillus-related diseases. Azole
      fungicides are also used in the wood industry, notably in sawmills, to protect
      wood from wood-destroying fungi. Through our study, we show that sawmills
      represent another professional environment affected by the presence of azole
      resistant A. fumigatus strains carrying the TR34 /L98H mutation. Moreover, this
      study provides valuable preliminary results to propose some new approaches to
      limit the emergence of azole-resistant A. fumigatus strains.

PMID- 28497647
TI  - Synthesis, Structure, and Reactivity of Ga-Substituted Distibenes and Sb
      Analogues of Bicyclo[1.1.0]butane.
AB  - Monovalent gallanediyl LGa {L=HC[C(Me)N(2,6-iPr2 C6 H3 )]2 } reacts with SbX3 to
      form the Ga-substituted distibenes [(LGaX)2 Sb2 ] (X=NMeEt 1, Cl 2). Upon
      heating, 2 reacts to the bicyclo[1.1.0]butane analogue [(LGaCl)2 (MU,eta1:1 -Sb4
      )] 3 containing a [Sb4 ]2- dianion. Moreover, 2 reacts with Li amides LiNR2 in
      salt elimination reactions that form the corresponding amido-substituted
      compounds 1 and [(LGaNMe2 )2 Sb2 ] 4, whereas reactions of 4 and [(LGaNMe2 )2
      (MU,eta1:1 -Sb4 )] 5 with two equivalents of GaCl3 resulted in the formation of 2
      and 3, respectively. 1, 2 and 3 were characterized by 1 H and 13 C NMR
      spectroscopy, elemental analysis, and single crystal X-ray diffraction. In
      addition, their bonding situation was analyzed by quantum chemical calculations.

PMID- 28497648
TI  - Intrahepatic cholangiojejunostomy for complex biliary stenosis after pediatric
      living-donor liver transplantation.
AB  - The treatment of biliary stenosis after pediatric LDLT is challenging. We
      describe an innovative technique of peripheral IHCJ for the treatment of patients
      with complex biliary stenosis after pediatric LDLT in whom percutaneous treatment
      failed. During surgery, the percutaneous biliary drainage is removed and a
      flexible metal stylet is introduced trough the tract. Subsequently, the most
      superficial aspect of the biliary tree is recognized by palpation of the stylet's
      round tip in the liver surface. The liver parenchyma is then transected until the
      bile duct is reached. A side-to-side anastomosis to the previous Roux-en-Y limb
      is performed over a silicone stent. Among 328 pediatric liver transplants
      performed between 1988 and 2015, 26 patients developed biliary stenosis. From
      nine patients requiring surgery, three patients who had received left lateral
      grafts from living-related donors due to biliary atresia were successfully
      treated with IHCJ. After a mean of 45.6 months, all patients are alive with
      normal liver morphological and function tests. The presented technique was a
      feasible and safe surgical option to treat selected pediatric recipients with
      complex biliary stenosis in whom percutaneous procedures or rehepaticojejunostomy
      were not possible, allowing complete resolution of cholestasis and thus avoiding
      liver retransplantation.

PMID- 28497649
TI  - Lanthanide Complexes that Respond to Changes in Cyanide Concentration in Water.
AB  - Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A
      derivatives in aqueous solution, giving rise to changes in the luminescence and
      NMR spectra. These changes are the consequence of cyanohydrin formation, which is
      favored by the coordination of the phenacyl carbonyl group to the lanthanide
      center. These complexes display minimal affinity for fluoride and can detect
      cyanide at concentrations less than 1 MUm. By contrast, lanthanide complexes with
      DOTAM derivatives display no affinity for cyanide in water, but respond to
      changes in fluoride concentration.

PMID- 28497650
TI  - Permanent Genetic Resources added to Molecular Ecology Resources Database 1 April
      2013-31 May 2013.

PMID- 28497651
TI  - Harnessing the power of digital droplet PCR to conduct real-world microbial
      competitions.
AB  - The budding yeast, Saccharomyces cerevisiae, has a long and storied history as a
      model organism for genetic, cellular and molecular biological research. More
      recently, researchers have sought to understand the ecology and evolution of its
      sister species, Saccharomyces paradoxus, in part to put our vast knowledge of the
      model yeast into its natural context (Replansky et al. ). However, the research
      tools have been limited, and most investigations into natural populations have
      either been descriptions of patterns of biogeography or taken the organism back
      into the laboratory for mating, growth and competition assays (Kuehne et al. ;
      Miller & Greig ; Murphy & Zeyl ; Samani et al. ). The link between what occurs
      out in the real world and what is measured in the laboratory has not yet been
      made, as so much is still unknown about the natural history of these yeasts. In
      this issue of Molecular Ecology Resources, Boynton et al. () take a major step
      towards bridging laboratory studies with field ecological research. By isolating
      a panel of S. paradoxus strains from a wooded area, culturing them in the
      laboratory, reintroducing pairs back into their habitat on natural substrate and
      monitoring the frequency of individual strains using digital droplet PCR, the
      researchers were able to use the framework of laboratory-based microbial
      competitions, but conduct them in a natural setting. While there is still more to
      learn about how to optimize this approach, it represents an exciting step in
      microbial ecological research and should prove an important tool for other
      species and numerous ecological questions.

PMID- 28497652
TI  - An isoflavone enriched diet increases skeletal muscle adaptation in response to
      physical activity in ovariectomized rats.
AB  - SCOPE: This study was to investigate anabolic adaptation of skeletal muscle in
      response to an isoflavone (ISO) enriched diet, training and their combinations in
      ovariectomized (OVX) rats. METHODS AND RESULTS: Female Wistar rats were
      sedentary, performed treadmill uphill running, received ISOs, or a combination of
      ISOs and running after ovariectomy. Body weight was increased by OVX. Both ISO
      and training treatment antagonized this increase. The weights of soleus and
      gastrocnemius muscles were increased only when training and ISOs were combined.
      In soleus muscle insulin-like growth factor (IGF)-1R, MyoD and Myogenin
      expressions were only up-regulated by training in Sham groups. However, a
      stimulation of IGF-1R and MyoD expression could be observed when ISOs and
      training were combined. In gastrocnemius muscle MyoD and Myogenin expressions
      were stimulated by either training or ISOs. Additive effects were detected when
      combining the two interventions. CONCLUSION: Our results indicate that the
      combination of ISOs and exercise is more efficient in increasing relative
      skeletal muscle mass and the expression of molecular markers related to anabolic
      adaptation in the skeletal muscle of female rats.

PMID- 28497653
TI  - Reply to Comment on "Flexible Asymmetric Supercapacitors Based on Nitrogen-Doped
      Graphene Hydrogels with Embedded Nickel Hydroxide Nanoplates".
AB  - In this reply to the Comment by Dr. Sascha Vongehr, the other authors of
      "Flexible Asymmetric Supercapacitors Based on Nitrogen-Doped Graphene Hydrogels
      with Embedded Nickel Hydroxide Nanoplates" present a rebuttal and clarify their
      interpretations of the issues he raised, arguing that numerous surmises and
      misinterpretations were made in the previous Comment.

PMID- 28497655
TI  - Nicotine self-administration reverses cognitive deficits in a rat model for
      schizophrenia.
AB  - High comorbidity between schizophrenia and tobacco addiction has been well
      established. Explanatory theories include nicotine as a cognitive enhancer
      ameliorating symptoms of schizophrenia and underlying shared substrates
      increasing susceptibility to addiction in these individuals. To test these non
      mutually exclusive theories, the maternal immune activation (MIA) model was
      utilized. To this end, pregnant Sprague Dawley rats were subcutaneously injected
      with a bacterial endotoxin, lipopolysaccharide (0.5 mg/kg), on gestation days 10
      and 11. Selective attention and working memory in adult male offspring were
      subsequently assessed using the latent inhibition and delayed non-matching to
      sample paradigms both before and after nicotine or saline self-administration.
      MIA led to deficits in both latent inhibition and delayed non-matching to sample
      in male offspring. Further, these animals showed a small but significantly
      increased responding for nicotine during self-administration acquisition,
      although there was no difference in dose-response effect or in progressive ratio
      testing. However, nicotine, but not saline self-administration, significantly
      ameliorated the cognitive deficits induced by MIA. While the male offspring of
      mothers prenatally exposed to lipopolysaccharide was only slightly more sensitive
      to the reinforcing effects of nicotine, after self-administration, the MIA
      induced cognitive deficits significantly improved. These data lend support for
      the self-medication hypothesis of schizophrenia.

PMID- 28497654
TI  - Oxidative Stickland reactions in an obligate aerobic organism - amino acid
      catabolism in the Crenarchaeon Sulfolobus solfataricus.
AB  - The thermoacidophilic Crenarchaeon Sulfolobus solfataricus is a model organism
      for archaeal adaptation to extreme environments and renowned for its ability to
      degrade a broad variety of substrates. It has been well characterised concerning
      the utilisation of numerous carbohydrates as carbon source. However, its amino
      acid metabolism, especially the degradation of single amino acids, is not as well
      understood. In this work, we performed metabolic modelling as well as metabolome,
      transcriptome and proteome analysis on cells grown on caseinhydrolysate as carbon
      source in order to draw a comprehensive picture of amino acid metabolism in S.
      solfataricus P2. We found that 10 out of 16 detectable amino acids are imported
      from the growth medium. Overall, uptake of glutamate, methionine, leucine,
      phenylalanine and isoleucine was the highest of all observed amino acids. Our
      simulations predict an incomplete degradation of leucine and tyrosine to organic
      acids, and in accordance with this, we detected the export of branched-chain and
      aromatic organic acids as well as amino acids, ammonium and trehalose into the
      culture supernatants. The branched-chain amino acids as well as phenylalanine and
      tyrosine are degraded to organic acids via oxidative Stickland reactions. Such
      reactions are known for prokaryotes capable of anaerobic growth, but so far have
      never been observed in an obligate aerobe. Also, 3-methyl-2-butenoate and 2
      methyl-2-butenoate are for the first time found as products of modified Stickland
      reactions for the degradation of branched-chain amino acids. This work presents
      the first detailed description of branched-chain and aromatic amino acid
      catabolism in S. solfataricus.

PMID- 28497656
TI  - Identification of atypical porcine pestivirus infection in swine herds in China.
AB  - Atypical porcine pestivirus (APPV) have been detected in swine herds from the
      USA, Germany, the Netherlands, Spain and most recently in Austria, suggesting a
      wide geographic distribution of this novel virus. Here, for the first time, we
      reported APPV infection in swine herds in China. Newborn piglets from two
      separate swine herds in Guangdong province were found showing typical congenital
      tremors in July and August 2016. RT-PCR, sequencing and phylogenetic analysis
      showed APPV infection occurred. Phylogenetic analysis showed that Chinese APPV
      strains, GD1 and GD2, formed independent branch from the USA, Germany and the
      Netherlands. Nucleotide identities between members of the APPV ranged between
      83.1% and 83.5%, and this showed APPV is highly diverse. It is apparent that this
      provides the first molecular evidence of APPV infection in swine herds in China.

PMID- 28497657
TI  - A rapid gene sequencing panel strategy to facilitate precision neonatal medicine.

PMID- 28497658
TI  - Toxic epidermal necrolysis in a child 6 months post-hematopoietic stem cell
      transplantation.
AB  - TEN is a rare and critical disease mostly caused by drugs. It is mediated by
      activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of
      cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic
      HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second
      complete remission. Although we did not evaluate the T-cell subpopulation in
      blood or skin lesion of the patient, an imbalanced immune reconstitution after
      HSCT might additively contribute to the development of TEN.

PMID- 28497659
TI  - Complete genome sequence of bluetongue virus serotype 4 that emerged on the
      French island of Corsica in December 2016.
AB  - In November 2016, sheep located in the south of Corsica island exhibited clinical
      signs suggestive of bluetongue virus (BTV) infection. Laboratory analyses allowed
      to isolate and identify a BTV strain of serotype 4. The analysis of the full
      viral genome showed that all the 10 genomic segments were closely related to
      those of the BTV-4 present in Hungary in 2014 and involved in a large BT outbreak
      in the Balkan Peninsula. These results together with epidemiological data suggest
      that BTV-4 has been introduced to Corsica from Italy (Sardinia) where BTV-4
      outbreaks have been reported in autumn 2016. This is the first report of the
      introduction in Corsica of a BTV strain previously spreading in eastern Europe.

PMID- 28497660
TI  - Chitosan brush for professional removal of plaque in mild peri-implantitis.
AB  - BACKGROUND: The aim of the study was to evaluate the effectiveness of a chitosan
      brush on the treatment of mild peri-implantitis. METHODS: Fifteen patients
      diagnosed with mild peri-implantitis contributing with single implant were
      treated with a chitosan brush. Modified plaque index (mPll), Modified Bleeding
      Index (mBoP) and probing depth (PPD) were recorded at baseline, 2, 4, 12 and 24
      weeks. Chitosan brush was used at 12 weeks if diagnosis was still present.
      Periapical radiographs were taken at the beginning of the study and 6 months
      after to control the stability of bone level. RESULTS: None of the patients
      reported discomfort or side effects during treatment. Bone level was maintained
      stable during the entire study. Plaque index remained almost 0 at every control
      visit. PPD and mBoP were significantly reduced at 2 weeks and when compared to
      baseline. At 24 weeks 73% of patients presented no further bleeding on probing
      with stable bone level. CONCLUSIONS: Chitosan brush could be a reliable
      instrument for the professionally administered plaque removal and resolution of
      clinical signs of initial stages of peri-implant inflammation.

PMID- 28497661
TI  - Medication-related osteonecrosis of the jaw: risk factors in patients under
      biphosphonate versus patients under antiresorptive-antiangiogenic drugs.
AB  - BACKGROUND: Biphosphonate-related osteonecrosis of the jaw (BRONJ) is a potential
      side effect associated with the administration of bisphosphonates; the aim of
      this work is to highlight the possible epidemiological differences between two
      groups of patients affected by medication related osteonecrosis of the jaw
      (MRONJ) treated at the Center of Oral Medicine, Pathology and Laser Surgery of
      the Academic Hospital at the University of Parma, Italy, between January 2004 and
      June 2016. METHODS: Medical charts of 303 patients (214 females and 89 males,
      mean age: 67 years old) treated at the Center of Oral Medicine, Pathology and
      Laser Surgery of the Academic Hospital at the University of Parma, between
      January 2004 and June 2016, were retrospectively analyzed. Patients were divided
      in 2 groups according to drugs therapy they underwent: group 1 (G1) including
      patients treated with bisphosphonates alone and group 2 (G2) including patients
      receiving antiresorptive-antiangiogenic drugs in association with bisphosphonates
      or antiresorptive-antiangiogenic drugs alone. Than 269 MRONJ sites treated with 5
      different therapeutical approaches were analyzed. RESULTS: Results showed G1
      consisting mainly in female patients undergoing bisphosphonates for oncologic
      disease, stage II was most frequently diagnosed and MRONJ developed mainly after
      dental extraction or bone surgery. G2 consisted mainly in males patients, whom
      took antiresorptive-antiangiogenic drugs in association with bisphosphonate or
      antiresorptive-antiangiogenic drugs alone for oncologic disease. Stage II was
      most frequently diagnosed and MRONJ developed most frequently "spontaneous".
      CONCLUSIONS: This study showed how a new population affected by MRONJ is
      emerging. Men affected by kidney cancer treated with new antiresorptive
      antiangiogenic drugs will represent a growing portion of the pool of patients at
      risk. In our experience, a strict follow-up is of outmost importance to early
      detect MRONJ also in patients with spontaneous cases. When MRONJ occurs, surgical
      laser treatment with Er:YAG seems to represent the option with highest percentage
      of success; for patients with contraindication to surgery, LLLT helps to improve
      outcomes of the medical therapy.

PMID- 28497662
TI  - Volatile sulphur compounds in exhaled air of dental students smoking the
      waterpipe: a nested case control study.
AB  - BACKGROUND: This study aims at investigating a potential adverse effect that
      waterpipe tobacco smoking may cause by comparing levels of volatile sulphur
      compounds in exhaled air of male dental students who smoke the waterpipe with
      those who do not smoke. METHODS: Dental students were categorized into waterpipe
      smokers and non-smokers. Volatile sulphur compounds were measured using a
      halimeter following the completion of questionnaire on smoking and oral hygiene
      habits and self-perceived halitosis. Statistics were carried out using ANOVA and
      relevant post hoc tests, associations were investigated using cross tabulation
      with the chi2 test. RESULTS: Results showed significantly higher levels of
      volatile sulphur compounds in: waterpipe smokers who smoke at least once a month
      when compared with non-smokers regardless their oral hygiene habits; subjects who
      do not brush their teeth; and subjects who self-perceive halitosis. There were no
      significant differences in these levels for similar groups on the basis of: use
      of floss, or use of mouth wash. CONCLUSIONS: It seems that waterpipe tobacco
      smoking results in increased volatile sulphur compounds levels in exhaled air.
      Oral hygiene practices like the use of tooth brush, dental floss, and mouth wash
      also seem to result in lower levels.

PMID- 28497663
TI  - Mortality risk prediction models for coronary artery bypass graft surgery:
      current scenario and future direction.
AB  - INTRODUCTION: Many risk prediction models are currently in use for predicting
      short-term mortality following coronary artery bypass graft (CABG) surgery. This
      review critically appraised the methods that were used for developing these
      models to assess their applicability in current practice setting as well as for
      the necessity of up-gradation. EVIDENCE ACQUISITION: Medline via Ovid was
      searched for articles published between 1946 and 2016 and EMBASE via Ovid between
      1974 and 2016 to identify risk prediction models for CABG. Article selection and
      data extraction was conducted using the CHARMS checklist for review of prediction
      model studies. Association between model development methods and model's
      discrimination was assessed using Kruskal-Wallis one-way analysis of variance and
      Mann-Whitney U-test. EVIDENCE SYNTHESIS: A total of 53 risk prediction models for
      short-term mortality following CABG were identified. The review found a wide
      variation in development methodology of risk prediction models in the field.
      Ambiguous predictor and outcome definition, sub-optimum sample size,
      inappropriate handling of missing data and inefficient predictor selection
      technique are major issues identified in the review. Quantitative synthesis in
      the review showed "missing value imputation" and "adopting machine learning
      algorithms" may result in better discrimination power of the models. CONCLUSIONS:
      There are aspects in current risk modeling, where there is room for improvement
      to reflect current clinical practice. Future risk modelling needs to adopt a
      standardized approach to defining both outcome and predictor variables, rational
      treatment of missing data and robust statistical techniques to enhance
      performance of the mortality risk prediction.

PMID- 28497664
TI  - Insulin sensitizers in adolescents with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the most common disorder of androgen excess
      in women of reproductive age. The diagnosis of PCOS can be more challenging in
      adolescents than in adult women given significant overlap between normal puberty
      and the signs of PCOS, including acne, menstrual irregularity, and polycystic
      ovarian morphology. Optimal treatments for adult women with PCOS vary depending
      on patient risk factors and reproductive goals, but mainly include hormonal
      contraception and insulin sensitizers. There is continued interest in targeting
      the intrinsic insulin resistance that contributes to metabolic and hormonal
      derangements associated with PCOS. The vast majority of published data on insulin
      sensitizing PCOS treatments are reported in adult women; these have included
      weight loss, metformin, thiazolidinediones, and the inositols. Furthermore, there
      is also a small but growing body of evidence in support of the use of insulin
      sensitizers in adolescents, with or without oral contraceptives. Discussion of
      the available treatments, including benefits, potential side effects, and
      incorporation of patient and family preferences is critical in developing a plan
      of care aimed at achieving patient-important improvements in PCOS signs and
      symptoms while addressing the longer-term cardiometabolic risks associated with
      the syndrome.

PMID- 28497665
TI  - Preoperative staging of rectal cancer using magnetic resonance imaging:
      comparison with pathological staging.
AB  - BACKGROUND: The aim of this study was to evaluate the accuracy of magnetic
      resonance (MR) in loco-regional staging of rectal cancer by comparing the MR
      results with histologic findings, considered as standard reference. METHODS:
      Between July 2013 and March 2015, fifty-two patients, 27 (51.9%) males, age
      66.75+/-13.77 years, with rectal cancer, were staged preoperatively with MR and
      proceeding straight to surgery. Two observers with experience in abdominal MR
      independently reviewed the images. T stage and N stage were evaluated according
      to the 7th edition of TNM classification. The estimate of Ln probability of
      malignancy (low, moderate, high) was based on nodal size, border contour and
      signal intensity and comparison between ADC value of the Ln's belonging to the
      three different classifications were performed. Statistical testing included
      Cohen's kappa coefficient, Mann-Whitney's, Kruskal-Wallis, chi2, Fisher's Exact
      Test and Receiving Operating Characteristics curve. RESULTS: MR correctly
      assessed T stage in 47/52 cases (90.4%; kw=0.89+/-0.06), with inter-operator
      concordance of k=0.81+/-0.08. For Ln staging, concordance between estimate of
      high probability malignancy and pathology was kw=0.62+/-0.11. ADC was
      significantly different for the three grades of estimated malignancy probability
      (P=0.0003), decreasing from 1.227+/-0.298*10-3 mm2/s (low) to 1.120+/-0.306*10-3
      mm2/s (moderate) and finally to 0.818+/-0.168*10-3 mm2/s (high). The ROC curve
      procedure established the good ability of ADC to discriminate high malignancy
      Ln's (AUC=0.88) with cut-off at <1*10-3 mm2/s. The percentage of high malignancy
      Ln's in the lateral pelvic space was higher than in other sites (55.6% vs. 17.6%,
      P=0.0003). CONCLUSIONS: MR is an accurate imaging method in T staging and N
      staging of rectal cancer: prediction of N was improved by considering dimension,
      morphology and signal characteristic and the ability of ADC to identify high
      probability malignant nodes underlines its importance in the diagnostic process.

PMID- 28497666
TI  - Serious dysphagia following anterior cervical discectomy and fusion: long-term
      incidence in a national cohort.
AB  - BACKGROUND: Although dysphagia is often self-limiting after anterior cervical
      discectomy and fusion (ACDF), its incidence, risks, and long-term outcomes remain
      unclear. The present study aimed to analyze dysphagia up to 5 years post-ACDF
      using a nation-scaled cohort. METHODS: Incidences of permanent dysphagia
      requiring nasogastric-tube feeding after ACDF were analyzed using three million
      sample cohorts derived from the National Health Insurance Research Database of
      Taiwan. All identified subjects were stratified into four groups (40s, 50s, 60s,
      and >70) according to their age at operation, and were subsequently followed up
      for 5 years. The risks of dysphagia were compared between the groups using Kaplan
      Meier analysis and Cox regression hazard ratio model. RESULTS: A total of 2,723
      patients (> 40 years old) who received first-time ACDF surgery were identified
      from a cohort of three million and followed up for a maximum of 5 years post
      operation. The 5-year incidence rates of persistent dysphagia (requiring use of a
      nasogastric tube) were 6.1, 4.0, 12.0, and 22.8 per 1,000 person-years for each
      age group (40s, 50s, 60s, and 70+ years old, respectively). The overall incidence
      rate of dysphagia after ACDF was 18.4, 10.9, and 8.9 per 1,000 person-years at 3
      months, 1 year, and 5 years follow-up, respectively. The incidence rates of
      dysphagia and use of home care services were highest at 3 months post-operation
      in all age groups, but dropped to a stable level after one year post-operation.
      The risks of dysphagia and the necessity of using home care services were higher
      (hazard ratio= 2.69 and 4.96) in the elderly group (aged 70 years and over) at
      all follow-up time points. CONCLUSION: The elderly patients had higher risks of
      short- and long-term severe dysphagia after ACDF. Therefore, although the
      incidence rates were still low (approximately 2.3%), older patients (aged 70
      years and over) should be cautioned for dysphagia requiring a nasogastric tube
      and home care services if they undergo ACDF.

PMID- 28497667
TI  - Midline Lumbar Fusion with cortical bone trajectory as first line treatment in a
      selected series of patients with lumbar instability.
AB  - OBJECT: Aim of the present study was to proof that for certain complex spinal
      conditions, MIDLIF technique is very convenient in terms of length of
      hospitalization, functional recovery and pain relief and time to back to work.
      METHODS: MIDLF indications were set for patients with not more than 3 unstable
      levels, presence of osteoporosis (alternative to cemented screws), or
      cardiomyopathy with anticoagulation with or without spinal stenosis, and or
      discopathy. Surgical difficulties, operative time, hemoglobin loss and
      postoperative 45 days, 6 months and one-year follow- up data are shown. RESULTS
      AND CONCLUSIONS: In one-year period MIDLF was applied for 9 patients. For all
      cases motor deficits improved, pain decreased from a high VAS score to VAS 1. No
      complications were seen so far. In one case small pedicles prevented the use of
      MIDLF technique. Operative time, acceptable hemoglobin loss, short length of stay
      and encouraging follow-up result indicate that this technique is a valid option
      to improve patient's quality of life where osteoporosis makes traditional trans
      pedicular screws less stable or where the surgeon has the need to reduce
      intraoperative blood loss or has to work in a deep surgical field.

PMID- 28497668
TI  - Potential brain dead organ donation in neurocritical care mortality.
AB  - BACKGROUND: Mortality is a marker of quality in neurocritical care, but it also
      provides potential for donors after brain death (DBD) following irreversible
      acute brain damage. The aim of this study was to analyse the neurointensive care
      unit (NICU) mortality rate and recovery of potential DBD. METHODS: We performed a
      10-year prospective observational cohort computer database analysis of 6138 acute
      neurological and neurosurgical patients (pts, 58.2% male, mean: age 55.9+/-14.7
      years, body weight 78.3+/-15.6 kg, body mass index 26.9+/-4.7, NICU stay 3.8+/
      5.3 days): 3462 (56.4%) pts with brain disease (mostly stroke 43.2%, tumour
      31.1%, trauma 13.6%); 10.3% pts with internal carotid artery (ICA) stenosis;
      32.6% pts with spine diseases, and others. Mean Acute Physiology and Chronic
      Health Evaluation (APACHE) II score on admission was 10.63+/-5.2 and Glasgow Coma
      Scale on admission was 13.79+/-2.51. RESULTS: There were 159 (2.6%) cases of
      mortality with a significantly higher mortality rate in pts with brain diseases
      (95.6% of deceased pts, p<0.001) than in ICA stenosis (0.6%), spine (1.9%) and
      from others (1.9%). There were 23 (14.5%) pts with clinical signs of brain death,
      of whom 13 (56.5%) became donors. The main reasons for non-recovery of potential
      donors were hemodynamic instability (16.7%) and family reluctance (12.5%).
      CONCLUSIONS: The study showed that our NICU mortality was 2.6%. There were
      relatively few clinical signs of brain death and not all potential donors were
      recovered.

PMID- 28497669
TI  - Mapping seizure foci and tumor genetic factors in glioma associated seizure
      patients.
AB  - BACKGROUND: Epilepsy, which is the most common symptom accompanying gliomas, was
      reported as an independent favorable prognosis factor for glioma patients.
      However, the correlation between glioma location and epilepsy prognosis, genesis
      and genetic phenotypes of the glioma associated seizure (GAS) patients is far
      from clear, the purpose of the current study was to provide probabilistic
      radiographic atlases reflecting seizure susceptible regions, relationship between
      tumor associated biomarkers and seizure initiation and poor epilepsy prognosis
      areas. METHODS: Preoperative MRIs were collected from 119 newly diagnosed
      patients with histologically confirmed gliomas. These samples were analyzed for
      seizure status and tumor genetic makers (TP53 mutations, MMP-9.PTEN, MGMT, EGFR
      and IDH1) using a statistical voxel-based lesion-symptom mapping (VLSM) method.
      RESULTS: We found bilaterally that the frontal lobe containing regions were
      associated with GAS for low grades gliomas, moreover lesions with the PTEN
      mutation and IDH1 mutation and seizure susceptible regions were located close
      together and partially overlapped, Patients with preoperative tumor involving the
      right frontal lobe may have good seizure control; however, for the glioma
      infiltrated regions in front of the precentral regions in the left hemisphere,
      the epilepsy prognosis is poor. CONCLUSIONS: The current results of seizure
      associated molecules and specific regions on structural MRI could be used in
      preoperative surgical planning, seizure prognosis predictions and anti-epilepsy
      drug usage.

PMID- 28497670
TI  - The role of diffusion tensor imaging in assessing the microstructural integrity
      of white matter in spinal cord concussions.

PMID- 28497671
TI  - Perceived efficacy and satisfaction of patients with subcutaneous hypoallergenic
      high-dose house dust mite extract.
AB  - Summary: The efficacy and safety of subcutaneous immunotherapy with modified,
      high-dose, major allergen house dust mite extract is widely supported by double
      blind, placebo-controlled studies. However, little is known regarding patient
      perceived efficacy and satisfaction. An observational, retrospective, multicentre
      study in patients treated with Acaroid(r) was conducted to assess the efficacy
      and degree of satisfaction of the patients after the first six months of
      treatment with it. All the clinical study procedures were performed according to
      the routine clinical practice. This study demonstrates that Acaroid(r) is
      effective and well tolerated. The patients' condition demonstrated a clear and
      marked improvement in the first 6 months after treatment initiation. Patients
      treated with Acaroid(r) were very satisfied, with a correlation to improvement in
      patient-perceived symptoms and the administration of treatment by a healthcare
      professional.

PMID- 28497672
TI  - Allergic and nonallergic rhinitis and skin sensitization to metals: is there a
      link?
AB  - Summary: Background. Chromium, Cobalt and Nickel are responsible for contact
      dermatitis, that is largely prevalent in the general population. They can act
      also as irritants in the upper and lower respiratory airways. Also rhinitis
      (allergic and nonallergic) is a high prevalence disorder. Both diseases could
      share some common inflammatory mechanisms, but the clinical association between
      skin sensitization to metals and rhinitis was never studied. Objective. We
      assessed the presence of skin sensitization to metals in subjects with rhinitis.
      Methods. Patients suffering from rhinitis underwent a standard diagnostic
      procedure, including skin testing, nasal endoscopy and nasal cytology. Control
      healthy subjects were also included. None of the patients had skin diseases. All
      subjects underwent patch test with Chromium, Cobalt and Nickel. Results. None of
      the 26 controls had positive skin prick test or nasal cytology. The 82 rhinitis
      patients were subdivided into allergic (group A = 27), nonallergic (group B = 31)
      and overlapping (group C = 24). The prevalence of positive patch test to metals
      was 26% in group A, 45% in group B, 42% in group C and 31% in controls. The
      percentage of patch-positive subjects was significantly different between Group A
      and B (p = 0.0045; OR: 0.43), Group A and C (p = 0.0186; OR: 0.49), and Group B
      and controls (p = 0.0360; OR: 1.85). There was a significant difference between
      groups A + controls and B + C. Conclusion. Even in the absence of skin diseases,
      the prevalence of sensitization to metals (patch test) is greater in nonallergic
      and overlapping rhinitis, as compared to allergic rhinitis and controls.

PMID- 28497673
TI  - Body Mass Index and skin reactivity to histamine and Dermatophagoides
      pteronyssinus in children and adolescents followed in a pediatric allergy
      service.
AB  - Summary: Rationale. Recent data suggest that the nutritional status assessed by
      body mass index (BMI) is positively associated with skin reactivity to histamine
      in children. Objective. To study the relation between BMI and skin reactivity to
      histamine and Dermatophagoides pteronyssinus in allergic children and
      adolescents. Methods. The medical charts of patients attended in our outpatient
      clinic between 2013 and 2014 (n = 972) were evaluated. Only patients with asthma,
      allergic rhinitis or wheezing infants sensitized to at least one aeroallergen
      were selected: a total of 626 patients (6 months to 19 year-olds; 60.1% male)
      were enrolled. Weight (kg), height (m), BMI (weight/height2), and the mean
      diameter of the wheals induced by histamine (10 mg/ml) and Dermatophagoides
      pteronyssinus in skin prick tests (SPT) were obtained. Skin index (SI; ratio of
      allergen-induced wheal diameter and corresponding histamine diameter) was also
      analyzed. Results. All patients had shown a mean wheal diameter of histamine
      greater than 1 mm. There was no increased skin reactivity to histamine with
      increasing BMI Z score (ZBMI). However, a significant correlation between BMI and
      the mean wheal of histamine was observed in patients < -1 ZBMI. Similar results
      were observed with Dermatophagoides pteronyssinus, (even considering the SI).
      Conclusions. We did not document interference of nutritional status (ZBMI) on the
      skin reactivity to histamine or Dermatophagoiodes pteronyssinus in atopic
      patients. Further investigation is required.

PMID- 28497674
TI  - The Vespid Allergy Quality of Life Questionnaire - cultural adaptation and
      translation to Portuguese.
AB  - Summary: A cross-cultural translation of the Vespid Allergy Quality of Life
      Questionnaire (VQLQ) to the Portuguese population (VQLQ-P) was performed,
      assessing its applicability in wasp and in non-beekeeper bee venom allergic
      patients. Additionally, we evaluated a Visual Analogue Scale (VAS) to estimate
      hymenoptera allergy interference with daily life. Methods. Cross-cultural
      translation was performed according to recommendations. The final VQLQ-P version,
      the Expectation of Outcome questionnaire (EoQ), EQ-5D and VAS were applied to
      wasp (n = 19) and non-beekeeper bee venom allergic patients (n = 30). Results.
      VQLQ-P significantly correlated with EoQ, (r = 0.76, p < 0.01), EQ-5D (usual
      activities and anxiety / depression dimensions) and VAS, with a good internal
      consistency (Cronbach alpha = 0.88) in wasp allergic individuals. VQLQ-P and EoQ
      correlation was also high (r = 0.67, p < 0.01) in bee allergy. Conclusion. The
      VQLQ-P is a valuable tool to evaluate quality of life impairment in Portuguese
      hymenoptera venom allergic individuals.

PMID- 28497675
TI  - Evaluation of pulmonary complications in patients with primary immunodeficiency
      disorders.
AB  - Summary: Background. Primary immunodeficiencies (PIDs) are inherited disorders in
      which one or several components of immune system are defected. Moreover, affected
      patients are at high risk for developing recurrent infections, particularly
      pulmonary infections. The spectrum of pulmonary manifestations in PIDs is broad,
      and includes acute and chronic infection, structural abnormalities (eg,
      bronchiectasis), malignancy and dysregulated inflammation resulting in tissue
      damage. In this study, our aims are to evaluate pulmonary complications in PID
      patients. Patients and Methods. We studied 204 cases with confirmed PID. To
      evaluate pulmonary complications in these patients, we used pulmonary function
      test (PFT), high resolution computed tomography (HRCT) scan and bronchoalveolar
      lavage (BAL). Results. Our results showed that pneumonia was the most frequent
      clinical manifestations in all PID patients. There were significantly greater
      numbers of episodes of pneumonia in HIgM, XLA and CVID patients with delayed
      diagnoses < 6 years. Moreover, of 57.4% CVID patients, 55% XLA patients and 33.3%
      HIgM patients had abnormal PFT results, and bronchiectasis was showed in 9
      (42.9%) of XLA, 6 (11.8%) of HIES, 3 (21.4%) of HIgM and 38 (62.3%) of CVID
      patients. Conclusion. Pulmonary complications should be considered in cases with
      PIDs especially in CVID cases.

PMID- 28497676
TI  - Assessment of validity and reliability of Drug Hypersensitivity Quality of Life
      Questionnaire: The Dutch experience.
AB  - Summary: Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is the
      first questionnaire that captures health related quality of life impact in
      patients with drug hypersensitivity. The aim of this study was to translate and
      validate the original Italian 15-item DrHy-Q for use among Dutch-speaking
      residents. We also compared the DrHy-Q scores obtained across countries. In a
      prospective cohort study, the Dutch DrHy-Q was completed by 124 patients (65.3%
      female, age 56.8 +/- 14.0) with a confirmed drug hypersensitivity. Median DrHy-Q
      score was 12 [0-88]. Validity and reliability of the DrHy-Q was confirmed
      through, 1, confirmatory factor analysis; 2, concurrent validity with a generic
      health related quality of life questionnaire (RAND-36); 3, internal consistency;
      and 4, test-retest reliability. A country specific difference in scores was
      observed.

PMID- 28497677
TI  - Successful of subcutaneous and oral hyposensitizing therapy in 30 patients.
AB  - Summary: Background. Pharmacotherapy and immunotherapy are the main treatment
      modalities for respiratory allergy. The aim of this paper has been to evaluate
      the efficacy and tolerability of subcutaneous and sublingual immunotherapy in
      association in allergic patients, and to demonstrate that the patients who have
      performed a second oral vaccination cycle after 4-5 years from the first
      subcutaneous treatment, derive benefits that may last for years. This is due to
      immune system's plasticity. Methods. The study was conducted in 30 allergic
      patients which had previously executed a full cycle of classical subcutaneous
      immunotherapy, with a partial remission of symptoms. After 4-5 years, they were
      subjected to sublingual immunotherapy for the same allergen, improving the
      results obtained. Results. All the patients reported a decrease or absence of
      clinical symptoms, a reduction in the use of anti-allergic drugs, and lower
      values of PRIST and RAST after the treatment. Conclusions. The results of this
      clinical study confirm the improvement of results when subcutaneous and
      sublingual immunotherapy are associated.

PMID- 28497678
TI  - Eosinophil fungal rhinosinusitis caused by Fusarium infection secondary to
      odontogenic maxillary sinus disease: when collaboration between otolaryngologist
      and allergologist leads to the correct diagnosis and therapy.
AB  - Summary: Rhinitis and sinusitis usually coexist and are concurrent in most
      individuals; thus, the correct terminology is now "rhinosinusitis". On the basis
      of numerous causative factors, often co-existing in the same patient, the
      diagnosis of rhinosinusitis is also made by a wide variety of practitioners
      (allergologists, otolaryngologists, pulmonologists, primary care physicians,
      paediatricians, and many others). Approximately 5-15% of the population suffers
      from chronic rhinosinusitis, and in 10-12% of them, it is of dental origin. The
      treatment of odontogenic maxillary sinus disease is directed to the management of
      the rhinosinusitis and of the odontogenic source. The widespread use of dental
      implants and reconstructive procedures for dental implant placement has led to
      new types of complication, as in this case report, due to chronic eosinophilic
      rhinosinusitis secondary to Fusarium infection in the maxillary sinus. The
      patient was initially evaluated by the allergologist, and subsequently
      successfully treated by the otolaryngologist with Functional Endoscopic Sinus
      Surgery. The advantages of endoscopic sinus surgery include more accurate
      visualization, no external incision, reduced soft tissue dissection, and reduced
      hospital stay. Chronic maxillary sinusitis of dental origin is a common disease
      that requires treatment of the sinusitis as well as of the odontogenic source.

PMID- 28497679
TI  - Disappearance of severe oral allergy syndrome following omalizumab treatment.
AB  - Summary: The first case of disappearance of apple-induced oral allergy syndrome
      in a birch pollen-allergic patient following omalizumab treatment is reported.
      This observation in a case of type 2 food allergy suggests that omalizumab is
      potentially an effective preventive treatment for patients with severe, type 1
      food allergies.

PMID- 28497680
TI  - Guanidinium-Based Polymerizable Surfactant as a Multifunctional Molecule for
      Controlled Synthesis of Nanostructured Materials with Tunable Morphologies.
AB  - Rationally and efficiently controlling the morphology of nanomaterials plays a
      crucial role in significantly enhancing their functional properties and expending
      their applications. In this work, a strategy for controlled synthesis of diverse
      nanostructured materials with tunable morphologies was developed using a
      guanidinium-based surfactant with a polymerizable pyrrole unit as a
      multifunctional molecule that can serve not only as a structure-directing agent
      for mesostucture formation but also as a monomer and carbon source. The unique
      self-assembly behavior of the guanidinium head group under different conditions
      allows the synthesized surfactants to form different aggregates and thus to
      produce silica nanomaterials with multiple morphologies (such as sphere, disk,
      fiber, and cocoon) in conjunction with sol-gel chemistry. Besides the
      mesostructured silicates, by further exploring the polymerization and
      carbonization features of pyrrole units that were densely packed in the formed
      silica nanochannels, diverse nanostructured materials such as mesostructured
      conducting polymers, carbon materials, and metal-nanoparticle (NP)-decorated
      forms could also be easily obtained in one-pot fashion for various applications,
      such as energy storage and catalysis. As a demonstration, carbon nanotubes and Pd
      NP-doped hollow carbon spheres were fabricated, which exhibited good specific
      capacitance (101.7 F g-1) at the scan rates of 5 mV s-1 and excellent catalytic
      performance (100% conversion for three cycles) in the Suzuki C-C coupling
      reaction, respectively. All of the results indicate that our strategy may open a
      new avenue for efficiently accessing diverse nanostructured materials with
      tunable morphologies for wide applications.

PMID- 28497681
TI  - pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine
      Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy.
AB  - In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid
      (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica
      nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA,
      which were employed as a drug delivery system loaded with doxorubicin (DOX) as a
      model drug for cervical cancer therapy. The chemical structure and properties of
      these NPs were characterized by transmission electron microscopy, X-ray
      photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering
      autosizer, thermogravimetric analysis, and Fourier transform infrared
      spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro
      drug release experiments showed pH-dependent and sustained drug release profiles
      that could enhance the therapeutic anticancer effect and minimize potential
      damage to normal cells due to the acidic microenvironment of the tumor. These
      MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was
      demonstrated by the in vitro cellular uptake and cellular targeting assay.
      Compared with that of free DOX and DOX-loaded NPs without the folic targeting
      ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying
      that they are a highly promising potential carrier for cancer treatments.

PMID- 28497682
TI  - Size-Dependent Regulation of Intracellular Trafficking of Polystyrene
      Nanoparticle-Based Drug-Delivery Systems.
AB  - Nanoparticles (NPs) have shown great promise as intracellular imaging probes or
      nanocarriers and are increasingly being used in biomedical applications. A
      detailed understanding of how NPs get "in and out" of cells is important for
      developing new nanomaterials with improved selectivity and less cytotoxicity.
      Both physical and chemical characteristics have been proven to regulate the
      cellular uptake of NPs. However, the exocytosis process and its regulation are
      less explored. Herein, we investigated the size-regulated endocytosis and
      exocytosis of carboxylated polystyrene (PS) NPs. PS NPs with a smaller size were
      endocytosed mainly through the clathrin-dependent pathway, whereas PS NPs with a
      larger size preferred caveolae-mediated endocytosis. Furthermore, our results
      revealed exocytosis of larger PS NPs and tracked the dynamic process at the
      single-particle level. These results indicate that particle size is a key factor
      for the regulation of intracellular trafficking of NPs and provide new insight
      into the development of more effective cellular nanocarriers.

PMID- 28497683
TI  - A Kinetic Pathway toward High-Density Ordered N Doping of Epitaxial Graphene on
      Cu(111) Using C5NCl5 Precursors.
AB  - Pristine graphene possesses high electrical mobility, but its low charge carrier
      density severely limits its technological significance. Past efforts to increase
      graphene's carrier density via chemical doping have shown limited successes,
      accompanied by substantial reductions in the mobility caused by disordered
      dopants. Here, based on first-principles calculations, we propose to grow
      graphene on Cu(111) via self-assembly of C5NCl5 molecular precursors to achieve
      high-density (1/6) and highly ordered nitrogen doping. Such a process relies on
      the elegant concerted roles played by the London dispersion, chemical, and
      screened Coulomb repulsive forces in enhancing molecular adsorption, facilitating
      easy dechlorination, and dictating the overall orientation of the C5N radicals,
      respectively. Further growth from the orientationally correlated graphene islands
      is accompanied by significantly minimized density of grain boundaries as the
      grains coalesce to form larger N-doped graphene sheets, which are further shown
      to possess superb electronic properties for future device applications. Initial
      kinetic processes involved in N-doped graphene growth using C5NH5 precursors are
      also investigated and contrasted with that of C5NCl5.

PMID- 28497684
TI  - Facile Growth of Caterpillar-like NiCo2S4 Nanocrystal Arrays on Nickle Foam for
      High-Performance Supercapacitors.
AB  - Ternary cobalt nickel sulfide as a novel and efficient electrode material in
      supercapacitors has recently gained extensive interests. Herein, we first report
      a highly conductive caterpillar-like NiCo2S4, composed of NiCo2S4 nanosheet core
      and nanowire shell grown on Ni foam via a facile and cost-effective chemical
      liquid process. Growth mechanism of the NiCo2S4 nanosheets@nanowires (NSNWs)
      structure was also investigated in detail by analyzing time-dependent
      experimental as well as the amount of additive ammonium fluoride in solution.
      Furthermore, the electrochemical measurements were performed among three
      different morphologies of NiCo2S4 including nanosheets, nanosheets@nanoparticles,
      and NSNWs structure, which were obtained from different reaction stages. Because
      the NSNWs structure has relatively high electroactive surface area, conductivity,
      and effective electron transport pathways, the as-prepared NiCo2S4 NSNWs
      structure comparing with two other morphologies exhibits the maximum specific
      capacity of 1777 F/g at 1 A/g and the highest capacitance retention (83% after
      3000 cycles) at a high scan rate of 10 A/g with a mass loading density of 4.0
      mg/cm2. These results indicate that the NiCo2S4 NSNWs structure has great
      potential in supercapacitors.

PMID- 28497685
TI  - Diastereoselective Synthesis of Chiral 2,3-Disubstituted Indolines via Formal
      [3+2]-Cycloaddition of Arynes with gamma-Amino-alpha,beta-unsaturated Esters.
AB  - A one step formal [3+2]-annulation protocol for the synthesis of 2,3
      disubstituted indolines is described. The in situ generated aryne acts as a two
      atom component, and gamma-amino-alpha,beta-unsaturated esters acting as a three
      atom component to construct indoline units in a highly regio- and
      diastereoselective manner with yields ranging from 63 to 80%.

PMID- 28497686
TI  - Enhancing the Durability and Carrier Selectivity of Perovskite Solar Cells Using
      a Blend Interlayer.
AB  - A mechanically and thermally stable and electron-selective ZnO/CH3NH3PbI3
      interface is created via hybridization of a polar insulating polymer,
      poly(ethylene glycol) (PEG), into ZnO nanoparticles (NPs). PEG successfully
      passivates the oxygen defects on ZnO and prevents direct contact between
      CH3NH3PbI3 and defects on ZnO. A uniform CH3NH3PbI3 film is formed on a soft
      ZnO:PEG layer after dispersion of the residual stress from the volume expansion
      during CH3NH3PbI3 conversion. PEG also increases the work of adhesion of the
      CH3NH3PbI3 film on the ZnO:PEG layer and holds the CH3NH3PbI3 film with hydrogen
      bonding. Furthermore, PEG tailors the interfacial electronic structure of ZnO,
      reducing the electron affinity of ZnO. As a result, a selective electron
      collection cathode is formed with a reduced electron affinity and a deep-lying
      valence band of ZnO, which significantly enhances the carrier lifetime (473 MUs)
      and photovoltaic performance (15.5%). The mechanically and electrically durable
      ZnO:PEG/CH3NH3PbI3 interface maintains the sustainable performance of the solar
      cells over 1 year. A soft and durable cathodic interface via PEG hybridization in
      a ZnO layer is an effective strategy toward flexible electronics and
      commercialization of the perovskite solar cells.

PMID- 28497688
TI  - Defocused Imaging of UV-Driven Surface-Bound Molecular Motors.
AB  - Synthetic molecular motors continue to attract great interest due to their
      ability to transduce energy into nanomechanical motion, the potential to do work
      and drive systems out-of-equilibrium. Of particular interest are unidirectional
      rotary molecular motors driven by chemical fuel or light. Probing the mechanistic
      details of their operation at the single-molecule level is hampered by the
      diffraction limit, which prevents the collection of dynamic positional
      information by traditional optical methods. Here, we use defocused wide-field
      imaging to examine the unidirectional rotation of individual molecular rotary
      motors on a quartz surface in unprecedented detail. The sequential occupation of
      nanomechanical states during the UV and heat-induced cycle of rotation are
      directly imaged in real-time. The approach will undoubtedly prove important in
      elucidating the mechanistic details and assessing the utility of novel synthetic
      molecular motors in the future.

PMID- 28497689
TI  - High-Performance Li-Ion Capacitor Based on an Activated Carbon Cathode and Well
      Dispersed Ultrafine TiO2 Nanoparticles Embedded in Mesoporous Carbon Nanofibers
      Anode.
AB  - A novel Li-ion capacitor based on an activated carbon cathode and a well
      dispersed ultrafine TiO2 nanoparticles embedded in mesoporous carbon nanofibers
      (TiO2@PCNFs) anode was reported. A series of TiO2@PCNFs anode materials were
      prepared via a scalable electrospinning method followed by carbonization and a
      postetching method. The size of TiO2 nanoparticles and the mesoporous structure
      of the TiO2@PCNFs were tuned by varying amounts of tetraethyl orthosilicate
      (TEOS) to increase the energy density and power density of the LIC significantly.
      Such a subtle designed LIC displayed a high energy density of 67.4 Wh kg-1 at a
      power density of 75 W kg-1. Meanwhile, even when the power density was increased
      to 5 kW kg-1, the energy density can still maintain 27.5 Wh kg-1. Moreover, the
      LIC displayed a high capacitance retention of 80.5% after 10000 cycles at 10 A g
      1. The outstanding electrochemical performance can be contributed to the
      synergistic effect of the well-dispersed ultrafine TiO2 nanoparticles, the
      abundant mesoporous structure, and the conductive carbon networks.

PMID- 28497690
TI  - Novel Electrochemiluminescence-Sensing Platform for the Precise Analysis of
      Multiple Latent Tuberculosis Infection Markers.
AB  - Latent tuberculosis infection (LTBI) is one of the major contributing factors for
      the high incidence of tuberculosis, and the low contents of LTBI markers in human
      serum present a great challenge for the diagnosis of LTBI. Here, we reported a
      novel electrochemiluminescence (ECL)-sensing platform for the precise analysis of
      multiple LTBI markers, interferon-gamma (IFN-gamma) and interleukin (IL)-2. In
      this approach, self-prepared carbon quantum dots (CQDs) and luminol were
      integrated onto gold nanoparticles (AuNPs), which were further enriched on the
      surface of magnetic bead (MB) to create two solid-phase ECL nanoprobes
      (MB@Au@CQDs and MB@Au@luminol) for improving the detection sensitivity
      efficiently. Graphene oxide (GO) and AuNPs were electrodeposited onto a patterned
      indium tin oxide (ITO) electrode with two spatially resolved areas in sequence to
      form two sensitive and stable sensing areas. IFN-gamma-antibody (Ab)1 and IL-2
      Ab1 were separately immobilized on the two sensing areas to capture the
      corresponding LTBI markers, which were further recognized by IFN-gamma-Ab2 and IL
      2-Ab2 labeled as MB@Au@CQDs and MB@Au@luminol. The ECL intensity depended
      linearly on the content of IFN-gamma and IL-2 in the range of 0.01-1000 pg mL-1,
      with a low detection limit of 10 fg mL-1. The proposed ECL-sensing platform is
      simple, sensitive, accurate, reliable, and specific to the detection of rare IFN
      gamma and IL-2 in human serum and provides a valuable protocol for facilitating
      fast and precise diagnosis of LTBI.

PMID- 28497692
TI  - Molecular Iodine-Mediated alpha-C-H Oxidation of Pyrrolidines to N,O-Acetals:
      Synthesis of (+/-)-Preussin by Late-Stage 2,5-Difunctionalizations of
      Pyrrolidine.
AB  - We previously reported an iterative synthesis of unsymmetrical 2,5-disubstituted
      pyrrolidines from pyrrolidine by two rounds of redox-triggered alpha-C-H
      functionalization. Although this approach can be used to introduce substituents
      at the 2- and 5-positions, it is lengthy because the redox auxiliary must be
      removed and then reinstalled. Therefore, we sought to develop a method to oxidize
      2-functionalized pyrrolidine to cyclic N,O-acetal which could then react with a
      nucleophile for introduction of the 5-substituent. In this work, we found that
      molecular iodine can mediate the preferential oxidation of secondary over
      tertiary alpha-C-H bonds of alpha-substituted pyrrolidines to form cyclic N,O
      acetals, improving the step economy of our previously reported method. With this
      strategy, (+/-)-preussin and its C(3) epimer were synthesized from (+/-)
      pyrrolidin-3-ol.

PMID- 28497691
TI  - Fine-Tuned Photoactive and Interconnection Layers for Achieving over 13%
      Efficiency in a Fullerene-Free Tandem Organic Solar Cell.
AB  - Fabricating organic solar cells (OSCs) with a tandem structure has been
      considered an effective method to overcome the limited light absorption spectra
      of organic photovoltaic materials. Currently, the most efficient tandem OSCs are
      fabricated by adopting fullerene derivatives as acceptors. In this work, we
      designed a new non-fullerene acceptor with an optical band gap (Egopt) of 1.68 eV
      for the front subcells and optimized the phase-separation morphology of a
      fullerene-free active layer with an Egopt of 1.36 eV to fabricate the rear
      subcell. The two subcells show a low energy loss and high external quantum
      efficiency, and their photoresponse spectra are complementary. In addition, an
      interconnection layer (ICL) composed of ZnO and a pH-neutral self-doped
      conductive polymer, PCP-Na, with high light transmittance in the near-IR range
      was developed. From the highly optimized subcells and ICL, solution-processed
      fullerene-free tandem OSCs with an average power conversion efficiency (PCE)
      greater than 13% were obtained.

PMID- 28497687
TI  - Eukaryotic Translesion DNA Synthesis on the Leading and Lagging Strands: Unique
      Detours around the Same Obstacle.
AB  - During S-phase, minor DNA damage may be overcome by DNA damage tolerance (DDT)
      pathways that bypass such obstacles, postponing repair of the offending damage to
      complete the cell cycle and maintain cell survival. In translesion DNA synthesis
      (TLS), specialized DNA polymerases replicate the damaged DNA, allowing stringent
      DNA synthesis by a replicative polymerase to resume beyond the offending damage.
      Dysregulation of this DDT pathway in human cells leads to increased mutation
      rates that may contribute to the onset of cancer. Furthermore, TLS affords human
      cancer cells the ability to counteract chemotherapeutic agents that elicit cell
      death by damaging DNA in actively replicating cells. Currently, it is unclear how
      this critical pathway unfolds, in particular, where and when TLS occurs on each
      template strand. Given the semidiscontinuous nature of DNA replication, it is
      likely that TLS on the leading and lagging strand templates is unique for each
      strand. Since the discovery of DDT in the late 1960s, most studies on TLS in
      eukaryotes have focused on DNA lesions resulting from ultraviolet (UV) radiation
      exposure. In this review, we revisit these and other related studies to dissect
      the step-by-step intricacies of this complex process, provide our current
      understanding of TLS on leading and lagging strand templates, and propose
      testable hypotheses to gain further insights.

PMID- 28497693
TI  - Palladium-Mediated Approach to Coumarin-Functionalized Amino Acids.
AB  - Incorporation of the fluorogenic l-(7-hydroxycoumarin-4-yl)ethylglycine into
      proteins is a valuable biological tool. Coumarins are typically accessed via the
      Pechmann reaction, which requires acidic conditions and lacks substrate
      flexibility. A Pd-mediated coupling is described between o-methoxyboronic acids
      and a glutamic acid derived (Z)-vinyl triflate, forming latent coumarins. Global
      deprotection with BBr3 forms the coumarin scaffold in a single step. This mild
      and scalable route yielded five analogues, including a probe suitable for use at
      lower pH.

PMID- 28497694
TI  - Stapled RGD Peptide Enables Glioma-Targeted Drug Delivery by Overcoming Multiple
      Barriers.
AB  - Malignant glioma, the most frequent and aggressive central nervous system (CNS)
      tumor, severely threatens human health. One reason for its poor prognosis and
      short survival is the presence of the blood-brain barrier (BBB) and blood-brain
      tumor barrier (BBTB), which restrict the penetration of therapeutics into the
      brain at different stages of glioma. Herein, inspired by the peptide stapling
      technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled
      RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB
      penetration and targeting ability to glioma cells. As expected, sRGD-modified
      micelles were able to penetrate the in vitro BBB model while retaining the glioma
      targeted capability. The results of the in vivo imaging studies further revealed
      that this nanocarrier could not only efficiently transverse the intact BBB of
      normal mice, but also could specifically target glioma cells of intracranial
      glioma-bearing nude mice. Furthermore, Paclitaxel-loaded sRGD-modified micelles
      exhibited improved antiglioma efficacy in vitro and significantly prolonged
      survival time of glioma-bearing nude mice. Overall, this sRGD peptide showed
      potency for glioma-targeted drug delivery by overcoming multiple barriers.

PMID- 28497695
TI  - Origin of in Situ Domain Formation of Heavily Nb-Doped Pb(Zr,Ti)O3 Thin Films
      Sputtered on Ir/TiW/SiO2/Si Substrates for Mobile Sensor Applications.
AB  - High-quality piezoelectric thin films have recently been in demand for mobile
      sensor applications. An investigation was conducted to understand the
      improvements in the piezoelectric and imprint characteristics of heavily Nb-doped
      lead zirconate titanate thin films with an extensive range of Nb content (up to
      14 mol %) beyond the typical solid solubility limit of Nb. The positive effects
      produced by the unusual doping of Nb were realized by utilizing an in situ
      sputtering process that did not require a subsequent annealing and poling
      procedure. An enhanced piezoelectric coefficient, -e31, of -12.87 C/m2 and a
      stronger shift in the coercive field, Ec,shift, of ~20 kV/cm, which are ideally
      useful for mobile sensor applications, were obtained for the 12 mol % Nb-doped
      films deposited on nonconventional buffer electrodes of Ir/TiW. The reduced
      oxygen vacancy concentration and preferred domain orientation with a stronger
      piezoresponse induced by the Nb donor doping contributed to the enhancement of
      the piezoelectric properties. Potential defect dipoles aligned by a residual
      stress gradient along columnar structures seemed to induce an internal electric
      field in the Nb-doped films, leading to the preferred domain orientation, as well
      as the strong imprint behavior due to a clamping of domain walls.

PMID- 28497696
TI  - Chemical Imaging by Dissolution Analysis: Localized Kinetics of Dissolution
      Behavior to Provide Two-Dimensional Chemical Mapping and Tomographic Imaging on a
      Nanoscale.
AB  - A new approach to achieving chemical mapping on a nanoscale is described that can
      provide 2D and tomographic images of surface and near-surface structure. The
      method comprises dissolving material from the surface of the sample by applying a
      series of aliquots of solvent, then analyzing their contents after removing them;
      in between exposures, the surface is imaged with atomic force microscopy. This
      technique relies on being able to compensate for any drift between images by use
      of software. It was applied to a blend of two polymers, PMMA and PS. The
      analytical data identified the material that was dissolved, and the topography
      images enabled the location of the various materials to be determined by
      analyzing local dissolution kinetics. The prospects for generalizing the approach
      are discussed.

PMID- 28497697
TI  - Synthetic Protein Scaffolds for Biosynthetic Pathway Colocalization on Lipid
      Droplet Membranes.
AB  - Eukaryotic biochemistry is organized throughout the cell in and on membrane-bound
      organelles. When engineering metabolic pathways this organization is often lost,
      resulting in flux imbalance and a loss of kinetic advantages from enzyme
      colocalization and substrate channeling. Here, we develop a protein-based
      scaffold for colocalizing multienzyme pathways on the membranes of intracellular
      lipid droplets. Scaffolds based on the plant lipid droplet protein oleosin and
      cohesin-dockerin interaction pairs recruited upstream enzymes in yeast ester
      biosynthesis to the native localization of the terminal reaction step, alcohol-O
      acetyltransferase (Atf1). The native localization is necessary for high activity
      and pathway assembly in close proximity to Atf1 increased pathway flux. Screening
      a library of scaffold variants further showed that pathway structure can alter
      catalysis and revealed an optimized scaffold and pathway expression levels that
      produced ethyl acetate at a rate nearly 2-fold greater than unstructured
      pathways. This strategy should prove useful in spatially organizing other
      metabolic pathways with key lipid droplet-localized and membrane-bound reaction
      steps.

PMID- 28497698
TI  - Orthogonal Chemical Modification of Template-Synthesized Nanostructures with DNA.
AB  - Very few chemical strategies for the selective functionalization of
      nanostructures have been developed despite their potential for controlling high
      order assembly processes. We report a novel approach for the selective chemical
      functionalization and localized assembly of one-dimensional nanostructures
      (rods), based upon the systematic activation (DNA functionalization) and
      passivation (self-assembled monolayers) of specific surface sites through the use
      of orthogonal chemical reactions on electrochemically grown metal nanorod arrays
      in porous anodic aluminum oxide templates. The ability to orthogonally
      functionalize the ends or the side of a nanorod, as well as the gaps between two
      rods, with different DNA strands allows one to synthesize nanostructure
      assemblies that would be difficult to realize any other way and that could
      ultimately be utilized for making a wide variety of device architectures.

PMID- 28497699
TI  - Humanitarian space and well-being: effectiveness of training on a psychosocial
      intervention for host community-refugee interaction.
AB  - Social and fieldworkers face enormous challenges in assisting millions of Syrian
      refugees in Lebanon since the Syrian war in 2011. We sought to assess the
      feasibility and acceptability of an adapted version of the SMART-3RP (Stress
      Management Relaxation Response Resilience Training) training to address the
      emotional and physical burden on the humanitarian field. Data were collected
      using the Symptom Checklist-90 (SCL-90), blood pressure, pulse and a brief
      qualitative survey at months 0, 3, 6 and 9. We compared mean SCL-90 scores and
      physiological measures from these time points and subjected qualitative data to a
      thematic analysis. Mean values of all measures decreased from months 0 to 9, with
      significance in SCL-90 changes increasing at each visit. Qualitative themes
      included decreased stress, increased positivity and problem-solving skills,
      interpersonal and personal benefits of mindfulness practice and the need to
      continue and expand the programme. Qualitative and quantitative analyses showed a
      decrease in stress perception and blood pressure, demonstrating the physiological
      benefits of mind body approaches. We highlight the importance of self-care for
      humanitarian workers as the basis for the mission's success. We invite additional
      research to confirm these findings and their implications for the humanitarian
      field.

PMID- 28497700
TI  - Instrumental Measurements of Water and the Surrounding Space During a Randomized
      Blinded Controlled Trial of Focused Intention.
AB  - The main goal of this work was the assessment of measurable interactions induced
      by focused intention, frequently used in biofield practices such as Healing Touch
      and Reiki. Water, as the main component of the human body, was chosen as a model.
      Intention experiments were performed over 4 different days at a scheduled
      interval, during which 286 trained biofield practitioners from several countries
      were instructed to meditate with the intention to change the molecular
      vibrational state of water samples selected by a blinded operator. The
      experimental protocol was randomized, blinded, and controlled; the measured
      variables included Raman spectra and the pH and electrical conductance of the
      water, as well as the magnetic field and UV-VIS (ultraviolet-visible) radiation
      near the experimental spot. Although a direct causal relationship cannot be
      established, some measurements of the water samples, as well as the magnetic
      field and radiation near the experimental spot, were responsive during the
      experimental period.

PMID- 28497701
TI  - Modified Qigong Breathing Exercise for Reducing the Sense of Hunger on an Empty
      Stomach.
AB  - BACKGROUND: The aims of this study were to determine whether a modified Qigong
      breathing exercise can reduce the sense of hunger and identify possible
      mechanisms. METHODS: The results from the test group, which performed the
      exercise, are compared with the control group, which performed deep breathing.
      Intestinal pressure measurements, stomach pH monitoring, and participant surveys
      were used for assessment. RESULTS: Stomach pH was increased by 3 (0.2) and
      intestinal pressure was reduced by 12 (0.5) mm Hg in the experimental group and
      did not change significantly in the control group. The study provides strong
      evidence that the exercise can significantly reduce, or even suppress the sense
      of hunger on an empty stomach. CONCLUSION: This breathing exercise provides
      comfort in different circumstances, such as lack of regular meals, limited volume
      or caloric diet, and even during temporary complete absence of food in
      therapeutic fasting.

PMID- 28497703
TI  - Association Between Media Doses of the Tips From Former Smokers Campaign and
      Cessation Behaviors and Intentions to Quit Among Cigarette Smokers, 2012-2015.
AB  - BACKGROUND: Since 2012, the Centers for Disease Control and Prevention (CDC) has
      implemented Tips From Former Smokers ( Tips), the first federally funded tobacco
      education campaign in the United States. To date, there are no evaluations of its
      long-term impact. AIMS: To assess the impact of varied doses of the Tips campaign
      from 2012 through 2015 on cessation-related behaviors and intentions among U.S.
      smokers. METHOD: We used a national probability-based online survey of cigarette
      smokers ( n = 22,189) and recent quitters ( n = 776) to examine associations
      between doses of Tips advertising, measured by gross rating points (GRPs), and
      intentions to quit smoking in the next 30 days and quit attempts within the past
      3 months. A curvilinear (i.e., square root) functional form of GRPs was used to
      capture patterns of diminishing effects at higher GRP levels. RESULTS: An
      increase of 1,000 quarterly Tips GRPs at the media market level was associated
      with increased odds of making a quit attempt in the past 3 months (adjusted odds
      ratio = 1.23, p < .001) and increased odds of intending to quit in the next 30
      days (adjusted odds ratio = 1.17, p = .030). DISCUSSION: Results suggest that CDC
      recommended media buys of 800 to 1,000 GRPs per quarter are sufficient to
      generate statistically significant increases in the likelihood of quit attempts
      in the past quarter. CONCLUSIONS: The Tips campaign has had a substantial impact
      on cessation behaviors among U.S. adult smokers over time. These data support the
      continued use of graphic and/or emotional media campaigns that encourage smokers
      to quit to further reduce tobacco use in the United States.

PMID- 28497704
TI  - What is the right dose of modern medicine?

PMID- 28497705
TI  - Circulating biomedical images: Bodies and chromosomes in the post-eugenic era.
AB  - This essay presents the early days of human cytogenetics, from the late 1950s
      until the mid 1970s, as a historical series of images. I propose a chronology
      moving from photographs of bodies to chromosome sets, to be joined by ultrasound
      images, which provided a return to bodies, by then focused on the unborn. Images
      carried ontological significance and, as I will argue, are principal characters
      in the history of human cytogenetics. Inspired by the historiography of heredity
      and genetics, studies on visual cultures, the conceptualization of circulation,
      and the sociology of pregnancy, I suggest that cytogenetics, through its focus on
      pregnancy, pregnant women, and their offspring, found strategic living materials
      that stabilized human chromosome studies as a biomedical, post-eugenics practice.
      The historicity of each path displays a wide circulation of objects, tools, and
      methods that condensed on images that shared in the centuries-old visual
      expertise that medicine and botany had manufactured.

PMID- 28497706
TI  - Striking ethnic variations in the epidemiology of Chlamydia trachomatis in Haifa
      District, Israel, throughout the years 2001-2015.
AB  - Our objectives were to examine trends in the incidence of chlamydia over an
      extended period and compare the epidemiology of the infection between two
      distinct ethnic groups in Israel: Jews and Arabs. We examined the incidence rate
      of Chlamydia trachomatis infection among residents of Haifa District, northern
      Israel from 2001 to 2015, by reviewing archives of the Department of
      Epidemiology, Ministry of Health. Notified cases were stratified by age group,
      gender, and ethnic group. The overall incidence rate of Chlamydia was 10.8 cases
      per 100,000 population per year. The annual rate increased dramatically from 5.1
      per 100,000 population in 2001, to an all-time high of 18.5 cases per 100,000
      population in 2015 (P < 0.001), representing an increase of 362.7%. The most
      affected age group was 25-34 years of age. The estimated rate among Jewish
      inhabitants was ninefold higher than among Arabs. Only 3% recurrent episodes of
      Chlamydia were registered. The prevalence of HIV positivity among Chlamydia
      infected patients was similar to that of the general population. In conclusion,
      Chlamydia in Haifa has been continuously increasing since 2001 and the infection
      is much more prevalent among patients of Jewish ethnicity, mainly due to more
      hazardous sexual practices in this population.

PMID- 28497707
TI  - Multiple physical healthcare needs among outpatients with schizophrenia: findings
      from a health examination study.
AB  - BACKGROUND: Despite the abundant literature on physical comorbidity, the full
      range of the concurrent somatic healthcare needs among individuals with
      schizophrenia has rarely been studied. AIMS: This observational study aimed to
      assess the distressing somatic symptoms and needs for physical health
      interventions in outpatients with schizophrenia, and factors predicting those
      needs. METHODS: A structured, comprehensive health examination was carried out,
      including a visit to a nurse and a general practitioner on 275 outpatients with
      schizophrenia. The required interventions were classified by type of disease.
      Logistic regression was used to assess the influence of sociodemographic factors,
      lifestyle, functional limitations, factors related to psychiatric disorder, and
      healthcare use on the need for interventions. RESULTS: In total, 44.9% of the
      patients (mean age 44.9 years) reported somatic symptoms affecting daily life;
      87.6% needed specific interventions for a disease or condition, most commonly for
      cardiovascular, dermatological, dental, ophthalmological, and gastrointestinal
      conditions, and for altered glucose homeostasis. Smoking and obesity predicted
      significantly a need of any intervention, but the predictors varied in each
      disease category. Strikingly, use of general practitioner services during the
      previous year did not reduce the need for interventions. CONCLUSIONS: Health
      examinations for outpatients with schizophrenia revealed numerous physical
      healthcare needs. The health examinations for patients with schizophrenia should
      contain a medical history taking and a physical examination, in addition to basic
      measurements and laboratory tests. Prevention and treatment of obesity and
      smoking should be given priority in order to diminish somatic comorbidities in
      schizophrenia.

PMID- 28497708
TI  - Salivary Gland Secretory Carcinoma With High-Grade Transformation, CDKN2A/B Loss,
      Distant Metastasis, and Lack of Sustained Response to Crizotinib.
AB  - BACKGROUND: Salivary gland secretory carcinoma is usually a low-grade neoplasm.
      However, high-grade transformation can occur and has important implications for
      clinical outcome. METHODS: A patient presented with an enlarging buccal mass.
      Magnetic resonance imaging (MRI) showed a tumor with a biphasic appearance along
      the right parotid duct. Local excision and histopathologic examination confirmed
      the diagnosis of secretory carcinoma with high-grade transformation. ETV6-NTRK3
      translocation and loss of CDKN2A/B were identified. RESULTS: The patient
      subsequently presented with cough and dyspnea and was found to have pleural
      metastases. Carboplatin and paclitaxel exacerbated the symptoms. Crizotinib
      resulted in initial symptomatic and radiographic improvement; however, the
      patient soon succumbed to progressive intrathoracic disease. CONCLUSIONS: High
      grade salivary gland secretory carcinoma can have a biphasic appearance on MRI.
      Diagnosis is confirmed by the histologic appearance and associated ETV6-NTRK3
      fusion. Additional molecular genetic events leading to transformation are
      unknown; however, loss of CDKN2A/B may have contributed. Treatment with
      multimodal chemotherapy was of limited benefit.

PMID- 28497709
TI  - Use of proximal side-hole micro-balloon catheter in transcatheter hepatic
      arterial chemoembolization.
AB  - We report on a 70-year-old man with unresectable multiple hepatocellular
      carcinomas who underwent treatment with transcatheter hepatic arterial
      chemoembolization. In treating a tumor in segment 1 of the liver, the proximal
      side-hole micro-balloon catheter, which has been newly developed, was useful.

PMID- 28497710
TI  - The Complex Diagnostic Challenge in Children With Non-Central Nervous System
      Cancer and Cerebellar Mutism.
AB  - Multiple etiologies should be considered in the differential diagnosis of
      immunocompromised patients with non-central nervous system cancer and viral
      infections who develop mutism. Acute cerebellitis, caused by infections or by
      neurotoxicity resulting from chemotherapy; paraneoplastic cerebellar
      degeneration; atypical posterior reversible encephalopathy syndrome; and acute
      disseminated encephalomyelitis may all cause mutism in such patients. This
      condition warrants prompt recognition and may require treatment with
      immunotherapy, as it may be an immune-mediated process. We present 2 patients
      with leukemia and viral illness who developed cerebellar mutism in the setting of
      acute cerebellitis and responded to immunotherapy, suggesting that the condition
      involved a parainfectious immune-mediated response.

PMID- 28497711
TI  - Production and covalent immobilisation of the recombinant bacterial carbonic
      anhydrase (SspCA) onto magnetic nanoparticles.
AB  - Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes with a pivotal potential
      role in the biomimetic CO2 capture process (CCP) because these biocatalysts
      catalyse the simple but physiologically crucial reaction of carbon dioxide
      hydration to bicarbonate and protons in all life kingdoms. The CAs are among the
      fastest known enzymes, with kcat values of up to 106 s-1 for some members of the
      superfamily, providing thus advantages when compared with other CCP methods, as
      they are specific for CO2. Thermostable CAs might be used in CCP technology
      because of their ability to perform catalysis in operatively hard conditions,
      typical of the industrial processes. Moreover, the improvement of the enzyme
      stability and its reuse are important for lowering the costs. These aspects can
      be overcome by immobilising the enzyme on a specific support. We report in this
      article that the recombinant thermostable SspCA (alpha-CA) from the thermophilic
      bacterium Sulfurihydrogenibium yellowstonense can been heterologously produced by
      a high-density fermentation of Escherichia coli cultures, and covalently
      immobilised onto the surface of magnetic Fe3O4 nanoparticles (MNP) via
      carbodiimide activation reactions. Our results demonstrate that using a benchtop
      bioprocess station and strategies for optimising the bacterial growth, it is
      possible to produce at low cost a large amount SspCA. Furthermore, the enzyme
      stability and storage greatly increased through the immobilisation, as SspCA
      bound to MNP could be recovered from the reaction mixture by simply using a
      magnet or an electromagnetic field, due to the strong ferromagnetic properties of
      Fe3O4.

PMID- 28497712
TI  - European General Practice Research Network (EGPRN)Abstracts from the EGPRN
      meeting in Leipzig, Germany, 12-16 October 2016. Theme: 'General practice/family
      medicine in a changing world'.

PMID- 28497713
TI  - Intention stability assessed using residual change scores moderates the intention
      behaviour association: a prospective cohort study.
AB  - Intention stability is considered to be one of the key pre-requisites for a
      strong association between intention and behaviour. It has been claimed, however,
      that studies examining the moderating impact of intention stability may be
      invalid, as they have relied on statistically inferior methods. Residual change
      scores have been suggested as a more appropriate method of measuring change (or
      lack thereof) in constructs. The aim of the current study, therefore, is to test
      whether intention stability, calculated using residual change scores, moderates
      the intention-physical activity behaviour association. A total of 163
      participants (124 women, 39 men) completed questionnaires online at three time
      points separated by 14 day intervals. The moderating impact of intention
      stability was assessed using multiple linear regression followed up using simple
      slope analyses to identify the direction of any effect. The interaction of
      intention and intention stability was found to significantly improve the overall
      model fit. Intentions had a stronger positive association with behaviour when
      intentions were more stable than when they were more unstable. However,
      sensitivity analyses revealed that the association was not robust and reduced to
      non-significant with the removal of potential multivariate outliers. Future
      research should use residual change scores as the preferred method of assessing
      intention stability.

PMID- 28497714
TI  - ECHO Autism: Using Technology and Mentorship to Bridge Gaps, Increase Access to
      Care, and Bring Best Practice Autism Care to Primary Care.

PMID- 28497715
TI  - Health Maintenance Deficits in a Fully Insured Population of Adolescents With
      Chronic Medical Conditions.
AB  - The current national monitoring of routine wellness care and vaccine uptake does
      not provide data on health maintenance among pediatric populations with chronic
      medical conditions. In this case-control study that analyzes wellness visits and
      vaccine uptake among adolescents, ages 16 to 18 years, we identified 938 without
      (controls) and 74 with (cases) 1 of 12 specific chronic medical conditions. The
      PPSV23 (23-valent pneumococcal polysaccharide vaccine) is recommended by the
      Advisory Committee on Immunization Practices for these 12 conditions and served
      as a measure of uptake for medically indicated vaccines. Our controls were twice
      as likely as cases to have a documented well visit in the past year, and there
      was a significantly higher proportion of controls than cases vaccinated with Tdap
      (tetanus toxoid, reduced diphtheria toxoid, acellular pertussis), MCV-4
      (quadrivalent meningococcal conjugate), and HPV (human papillomavirus), all P <
      .05. More than 60% of cases failed to receive PPSV23. Adolescents with chronic
      medical conditions are at high risk of neglecting routine health maintenance.

PMID- 28497716
TI  - Polyglucosan Bodies in Placental Extravillious Trophoblast for the Diagnosis of
      Fatal Perinatal Neuromuscular-type Glycogen Storage Disease Type IV.
AB  - The fatal infantile neuromuscular type is the most severe form of glycogen
      storage disease type IV (GSD IV). We report a case of a 22-day-old female neonate
      born at 34 weeks gestation with polyhyramnios, fetal hydrops, and severe
      hypotonia. Placental examination revealed numerous periodic acid schiff-positive
      diastase-resistant polyglucosan bodies in the cytoplasm of extravillous
      trophoblast predominantly in the placental basal plate. Muscle biopsy and autopsy
      findings supported a diagnosis of neuromuscular-type glycogen storage disease
      type IV with extensive involvement of skeletal muscle, heart, and liver. The
      diagnosis was confirmed by molecular genetic testing. We could only find 1 prior
      report in the English literature that describes placental pathological changes.
      Our findings suggest that placental examination can be a useful adjunct for early
      diagnosis, as placentas are often received for pathological examination shortly
      after birth and usually before a diagnostic muscle biopsy can be performed.
      Pathologists need to be aware of characteristic placental features.

PMID- 28497717
TI  - Optic Nerve Calcifications of Unknown Etiology in a 24-week-old Fetus.

PMID- 28497719
TI  - Moral Hindsight.
AB  - How are judgments in moral dilemmas affected by uncertainty, as opposed to
      certainty? We tested the predictions of a consequentialist and deontological
      account using a hindsight paradigm. The key result is a hindsight effect in moral
      judgment. Participants in foresight, for whom the occurrence of negative side
      effects was uncertain, judged actions to be morally more permissible than
      participants in hindsight, who knew that negative side effects occurred.
      Conversely, when hindsight participants knew that no negative side effects
      occurred, they judged actions to be more permissible than participants in
      foresight. The second finding was a classical hindsight effect in probability
      estimates and a systematic relation between moral judgments and probability
      estimates. Importantly, while the hindsight effect in probability estimates was
      always present, a corresponding hindsight effect in moral judgments was only
      observed among "consequentialist" participants who indicated a cost-benefit trade
      off as most important for their moral evaluation.

PMID- 28497720
TI  - Neuroscience and Ethics.
AB  - A number of people believe that results from neuroscience have the potential to
      settle seemingly intractable debates concerning the nature, practice, and
      reliability of moral judgments. In particular, Joshua Greene has argued that
      evidence from neuroscience can be used to advance the long-standing debate
      between consequentialism and deontology. This paper first argues that charitably
      interpreted, Greene's neuroscientific evidence can contribute to substantive
      ethical discussions by being part of an epistemic debunking argument. It then
      argues that taken as an epistemic debunking argument, Greene's argument falls
      short in undermining deontological judgments. Lastly, it proposes that accepting
      Greene's methodology at face value, neuroimaging results may in fact call into
      question the reliability of consequentialist judgments. The upshot is that
      Greene's empirical results do not undermine deontology and that Greene's project
      points toward a way by which empirical evidence such as neuroscientific evidence
      can play a role in normative debates.

PMID- 28497718
TI  - The biomechanical effects and perceived comfort of textile-fabricated insoles
      during straight line walking.
AB  - BACKGROUND: Orthotic insoles that are made of foam material often have less
      breathability and thus cause discomfort to the wearer. Given that a sandwich
      structure offers better porosity and breathability that would improve comfort,
      the impact of custom-made insoles made with three-dimensional spacer fabric is
      studied. OBJECTIVES: To examine the biomechanical effects and subjective comfort
      of spacer-fabric insoles during walking. STUDY DESIGN: Repeated measures.
      METHODS: Plantar pressure and lower limb muscle activity data are collected from
      12 subjects. Subjective perceived comfort is measured after five successful
      walking trials for each of the three different insoles worn: traditional insoles
      made with ethylene vinyl acetate and two types of spacer-fabric insoles. RESULTS:
      Compared to the use of traditional insoles, there is a statistically significant
      reduction in the peak pressure (>8%) and pressure-time integral (>16%) in the
      toes and metatarsal head 1 with the use of the spacer-fabric insoles as the top
      layer. Insoles with two layers of spacer fabrics have the highest perceived
      comfort ( p < 0.01). However, there is no significant difference in the selected
      muscle activity for all three insoles. CONCLUSION: Insoles with different
      arrangements of spacer fabrics allow changes in pressure patterns across the
      plantar foot and perception of comfort while walking. The findings enhance
      current understanding on the use of textile-fabricated materials, which provide
      alternative solutions for modifying insoles. Clinical relevance The key features
      of spacer fabric offer a viable option for different orthotic insole
      applications. The results will greatly contribute toward insole prescription,
      potentially enhancing the efficacy of orthotic performance and increasing the
      range of insole materials.

PMID- 28497721
TI  - Scale Effects in Moral Relevance Assessment.
AB  - Research on moral judgment often employs bipolar rating scales to assess whether
      the difference between two contrasted options is judged to be morally relevant.
      We give an account of how different numbers of response options provided on such
      scales (odd vs. even) change the meaning of the test question by communicating
      different implicit presuppositions. We demonstrate experimentally that these
      changes can qualitatively affect the moral relevance judgments that subjects
      express in response to a given judgment problem. Several alternative explanations
      in terms of trivial measurement distortion are tested and refuted, and we present
      suggestive evidence as to what kind of factors might be prone to scale effects.
      The findings underscore that expressed moral judgments are constructed ad hoc and
      do not necessarily reflect the content of underlying stable moral commitments. We
      discuss implications for theories and methodology in moral psychology and in
      judgment and decision-making research more generally.

PMID- 28497722
TI  - Moral Severity is Represented as a Domain-General Magnitude.
AB  - The severity of moral violations can vary by degree. For instance, although both
      are immoral, murder is a more severe violation than lying. Though this point is
      well established in Ethics and the law, relatively little research has been
      directed at examining how moral severity is represented psychologically. Most
      prominent moral psychological theories are aimed at explaining first-order moral
      judgments and are silent on second-order metaethical judgments, such as
      comparisons of severity. Here, the relative severity of 20 moral violations was
      established in a preliminary study. Then, a second group of participants were
      asked to decide which of two moral violations was more severe for all possible
      combinations of these 20 violations. Participant's response times exhibited two
      signatures of domain-general magnitude comparisons: we observed both a distance
      effect and a semantic congruity effect. These findings suggest that moral
      severity is represented in a similar fashion as other continuous magnitudes.

PMID- 28497723
TI  - The Intention-Outcome Asymmetry Effect.
AB  - Knowledge of intention and outcome is integral to making judgments of
      responsibility, blame, and causality. Yet, little is known about the effect of
      conflicting intentions and outcomes on these judgments. In a series of four
      experiments, we combine good and bad intentions with positive and negative
      outcomes, presenting these through everyday moral scenarios. Our results
      demonstrate an asymmetry in responsibility, causality, and blame judgments for
      the two incongruent conditions: well-intentioned agents are regarded more morally
      and causally responsible for negative outcomes than ill-intentioned agents are
      held for positive outcomes. This novel effect of an intention-outcome asymmetry
      identifies an unexplored aspect of moral judgment and is partially explained by
      extra inferences that participants make about the actions of the moral agent.

PMID- 28497724
TI  - Explaining Moral Behavior.
AB  - In this review we make a simple theoretical argument which is that for theory
      development, computational modeling, and general frameworks for understanding
      moral psychology researchers should build on domain-general principles from
      reasoning, judgment, and decision-making research. Our approach is radical with
      respect to typical models that exist in moral psychology that tend to propose
      complex innate moral grammars and even evolutionarily guided moral principles. In
      support of our argument we show that by using a simple value-based decision model
      we can capture a range of core moral behaviors. Crucially, the argument we
      propose is that moral situations per se do not require anything specialized or
      different from other situations in which we have to make decisions, inferences,
      and judgments in order to figure out how to act.

PMID- 28497725
TI  - Factors Guiding Moral Judgment, Reason, Decision, and Action.

PMID- 28497726
TI  - EDITORIAL: Neuroprotection Mechanisms and their Potential Applications.

PMID- 28497728
TI  - [Give itself the ways to listen to a different voice].

PMID- 28497729
TI  - [Optimization and safety assessment of Akkermansia muciniphila for human
      administration].

PMID- 28497731
TI  - [XBP1 and inflammation in cystic fibrosis alveolar macrophages].

PMID- 28497730
TI  - [Development of GnRH neurons in humans: new insights from 3D-imaging of fetal
      brains].

PMID- 28497732
TI  - [Combined adaptation of roots to flooding and soil nutrients: Role of a MAP3K
      protein kinase].

PMID- 28497733
TI  - [microRNA and inactivation of the pituitary gonadotrope function].

PMID- 28497734
TI  - [Focusing on the functional impact of retinal prothesis].

PMID- 28497735
TI  - [Endogenous retroviral sequences in the human genome can play a physiological or
      pathological role].
AB  - Human endogenous retroviruses (HERV) represent a large part of our genome and the
      few elements that have retained a potential of expression still remain "dormant"
      in physiological conditions. In some instances, they can be awakened by
      environmental factors activating their expression. The best studied conditions of
      HERV activation are infections caused by microorganisms such as viruses of the
      Herpesvirus family. This activation can thus lead to the expression of pathogenic
      proteins such as envelope proteins belonging to the HERV-W and HERV-K families,
      respectively involved in Multiple Sclerosis (MS) and amyotrophic lateral
      sclerosis (ALS). Endogenous retroviral proteins can also acquire a physiological
      function beneficial for humans. This is the case of Syncytin-1 from the HERV-W
      family, that is involved in placenta formation.

PMID- 28497736
TI  - [Implication of human endogenous retroviruses in schizophrenia and bipolar
      disorder].
AB  - Schizophrenia and bipolar disorder are neuropsychiatric disorders of unknown
      origin. It seems that these two disorders share some common etiopathogenic
      mechanisms including genetic, environmental and inflammatory ones. Reactivation
      of the human endogenous retrovirus type W (HERV-W) can be a shared element in the
      pathophysiology of schizophrenia and bipolar disorder, linked to immuno-genetic
      and environment risk factors. We will present studies that have highlighted the
      presence of HERV-W in schizophrenic and bipolar disorder patients. We will then
      describe a two-hit model which could explain the common pathophysiological
      mechanism of affective and non-affective psychosis. Identification of immuno
      inflammatory mediated subgroup of schizophrenia and bipolar disorder associated
      to HERV-W reactivation might open the way for the development of diagnostic
      biomarker and more targeted treatments. These new tools pave the way towards
      personalized psychiatry for a better care of patients.

PMID- 28497737
TI  - [Phage therapy: a realistic weapon against multidrug resistant bacteria].
AB  - The continuous increase in antibiotic resistance among bacteria in infectious
      diseases associated with the lack of new antibiotics able to circumvent them are
      urging physicians, researchers and politicians to look for others options for
      treatments. Among those, phage therapy (use of natural viruses that infect
      bacteria, called bacteriophages) is one of the most promising approaches. In this
      review, we first focus on the problematic raised by multidrug resistant bacteria
      before addressing the main biological characteristics of bacteriophages, as well
      as the credibility and the relevance of phage therapy. We then introduce human
      applications, their potentials and limits.

PMID- 28497738
TI  - [Osteocalcin and glucose metabolism: assessment of human studies].
AB  - Osteocalcin, a protein secreted by osteoblasts, is recognized as a biomarker of
      bone mineralization. Besides, animal experimental studies have shown that
      osteocalcin could play an important role in glucose metabolism. Over the course
      of the last decade, this theory has been investigated in several human studies.
      Most of the results obtained from these reports support a positive correlation
      between total and undercarboxylated osteocalcin and insulin
      secretion/sensitivity. Studies also corroborate a reverse association with
      glycemic parameters such as fasting glucose and glycated hemoglobin.
      Nevertheless, because most of the studies published are observational, it is not
      possible to yet confirm a direct cause-effect relationship. Research in the field
      will surely contribute to the development of new pharmacological strategies for
      the treatment of endocrine diseases.

PMID- 28497739
TI  - [Modelling of the blood-brain barrier].
AB  - The blood-brain barrier (BBB) is located at the brain microvessel level and
      isolates the brain from the whole body, thus restricting molecule and cell
      exchanges between cerebral and peripheral compartments. In order to better
      decipher and understand the BBB physiology and development, and to investigate
      transport mechanism and toxicity of neuropharmaceuticals, several in vitro BBB
      models have been developed using animal or human cells, primary or immortalized
      cells. The aim of this review is to explain to the reader the major criteria
      required for a pertinent in vitro BBB model and to briefly expose the different
      models currently available with their characteristics with a special focus on the
      static models.

PMID- 28497740
TI  - [The PIG-A gene as a new biomarker of mutagenesis: proof of concept and technical
      specifications].
AB  - Gene mutations are not directly detected by current genotoxicity assays and most
      of them need a cell culture step. The whole blood PIG-A assay consists in the
      detection of the mutation frequency within the PIG-A sentinel gene by
      identification of glycosyl-phosphatidyl-inositol (GPI-) deficient cells. PIG-A
      mutated/GPI-deficient cells can be detected by flow cytometry as they no longer
      express surface fluorescence for GPI-linked markers. The last researches have
      focused on cell enrichment techniques leading to increased throughput and
      sensitivity. The results of this new and promising biomarker of mutagenesis,
      performed in humans or rodents, are now available within 2 hours after blood
      collection.

PMID- 28497741
TI  - [Cancer screening fantasies].
AB  - The use of circulating tumour DNA to screen for cancer in asymptomatic
      individuals is the goal of Grail, initially set up by Illumina. This company is
      now raising a large amount of capital to develop this project on a much longer
      time scale than initially announced. Although it has access to cutting edge
      technology and is led by excellent scientists, the prospect for success in this
      application is rather bleak, mainly because of the extreme requirements for
      specificity in order to avoid overdiagnosis.

PMID- 28497742
TI  - [Relativism, ambiguities and non-alternative scientific facts].

PMID- 28497744
TI  - First molecular investigation of Cryptosporidium spp. in young calves in Algeria.
AB  - To date, no information is available on the prevalence and genetic identity of
      Cryptosporidium spp. in cattle in Algeria. In this study, 17 dairy farms in the
      province of Batna, located in the northeast of the country, were visited to
      collect 132 fecal samples from young calves (< 8 weeks old). Samples were
      examined microscopically using the modified Ziehl-Neelsen acid-fast staining
      method, and at least one sample per farm was submitted for molecular analysis.
      Amplification of a fragment of the small subunit ribosomal RNA gene was positive
      for 24 of the 61 samples (40%), and sequence analysis identified three species,
      namely Cryptosporidium bovis (n = 14), C. ryanae (n = 6), and C. parvum (n = 4).
      The C. parvum IIaA13G2R1 subtype, an uncommon zoonotic subtype, was identified in
      two isolates from a single farm by sequencing a fragment of the GP60 gene. This
      is the first report about genotyping and subtyping of Cryptosporidium in calves
      in Algeria.

PMID- 28497743
TI  - Seroprevalence of Theileria equi and Babesia caballi in horses in Spain.
AB  - Equine piroplasmoses are enzootic parasitic diseases distributed worldwide with
      high incidence in tropical and subtropical regions. In Spain, there is
      insufficient epidemiological data about equine piroplasmoses. The main aim of the
      present study was therefore to estimate the prevalence of Theileria equi and
      Babesia caballi in five regions and obtain information about the risk factors.
      This study was conducted in the central and south-western regions of Spain, using
      indirect fluorescence antibody testing (IFAT) in 3,100 sera samples from
      apparently healthy horses of different ages, breeds, coat colours, genders and
      geographical locations. The overall seroprevalence was 52%, consisting of 44%
      seropositive for T. equi and 21% for B. caballi. There was a significant
      association between age (p < 0.0001), breed (p < 0.004), geographical location (p
      < 0.0001) and the seroprevalence, but neither the coat colour nor the gender was
      significantly associated with prevalence. In addition, it was proved that most of
      the geographic areas showed a moderate to high prevalence. The statistical kappa
      value was used to compare the results obtained by the IFAT and the competitive
      enzyme-linked immunosorbent assay (cELISA) utilised to test some samples (n =
      108) and showed a higher concordance for T. equi (kappa = 0.68) than for B.
      caballi (kappa = 0.22). Consequently, this revealed the importance of developing
      an appropriate technique to detect each haemoparasite.

PMID- 28497746
TI  - The opioid crisis: the needle and the damage done.

PMID- 28497745
TI  - Preventive efficacy of NexGard Spectra(r) against Dipylidium caninum infection in
      dogs using a natural flea (Ctenocephalides felis) infestation model.
AB  - The efficacy of a monthly oral endectocide product, NexGard Spectra(r) (Merial),
      a combination of afoxolaner and milbemycin oxime, was evaluated in a flea
      (Ctenocephalides felis) challenge model for the prevention of Dipylidium caninum
      tapeworm infection in dogs. The efficacy of treatment with NexGard Spectra(r) was
      assessed in 10 dogs following weekly flea infestation with metacestode naturally
      infected fleas and compared with that in 10 untreated control dogs. The 100 fleas
      deposited weekly on each dog were not removed until Day 35, allowing enough time
      for their ingestion. The microscopical analysis of 30 fleas from the flea batches
      before each weekly challenge demonstrated that 10-33% of the fleas were infected
      by D. caninum cysticercoid larvae. The arithmetic mean flea count recorded was
      47.7 for the 10 untreated dogs and 0 for the 10 treated dogs at Day 35. Based on
      the daily collection of expelled D. caninum proglottids by dogs during the 70
      days of the study, 70% (7/10) of the control dogs and 0% (0/10) of the treated
      dogs were infected with D. caninum (p < 0.0031). Through its efficacy against
      fleas, NexGard Spectra(r) treatment provided indirect prevention of D. caninum
      infestation. No treatment-related adverse events were observed in dogs during
      this study.

PMID- 28497747
TI  - Stem-cell transplantation for Crohn's disease: same authors, different
      conclusions?

PMID- 28497748
TI  - The role (if any) of chemotherapy in hepatocellular carcinoma.

PMID- 28497749
TI  - PARP inhibitors and chemoradiation for rectal cancer.

PMID- 28497750
TI  - Paediatric liver disease: lessons for adult practice.

PMID- 28497751
TI  - Early age at diagnosis of hepatocellular carcinoma in sub-Saharan Africa.

PMID- 28497752
TI  - Early age at diagnosis of hepatocellular carcinoma in sub-Saharan Africa -
      Authors' reply.

PMID- 28497755
TI  - Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an
      analysis of pooled data from the ASTIC trial.
AB  - BACKGROUND: The randomised controlled ASTIC trial showed no benefit of
      mobilisation and autologous haematopoietic stem-cell transplantation (HSCT)
      compared with mobilisation followed by conventional therapy using a stringent
      primary endpoint (steroid-free clinical remission for 3 months with no endoscopic
      or radiological evidence of intestinal inflammation) in patients with treatment
      refractory Crohn's disease. We now assess HSCT in patients enrolled in the ASTIC
      trial using endpoints that are traditional for clinical trials in Crohn's
      disease, and identify factors that predict benefit or harm. METHODS: Patients who
      underwent mobilisation and were randomly assigned to conventional therapy in the
      ASTIC trial were offered HSCT at 1 year and underwent complete assessment for a
      further year. We report analyses of the combined cohort of patients who underwent
      HSCT at any time during the ASTIC trial programme. The primary outcome for this
      analysis was 3-month steroid-free clinical remission at 1 year after HSCT
      (Crohn's Disease Activity Index [CDAI] <150). We also examined the degree of
      endoscopic healing at 1 year. Multivariate analysis was performed to identify
      factors associated with achieving the primary endpoint by using logistic
      regression, and factors associated with experiencing a serious adverse event
      using Poisson regression. Participants were not masked to treatment, but the
      adjudication panel that reviewed radiology and endoscopy was masked to allocation
      and visits. All patients who underwent HSCT and had data available at baseline
      and 1-year follow-up were included in the primary and safety analysis. This trial
      is registered with ClinicalTrials.gov, number NCT00297193. FINDINGS: Between June
      28, 2007, and Sept 1, 2011, 45 patients were enrolled in the ASTIC trial from 11
      European transplant units. 23 patients were randomly assigned to immediate HSCT,
      and 22 patients were assigned to mobilisation followed by conventional care.
      After completion of the ASTIC trial, 17 patients from the conventional care group
      received HSCT. In the combined cohort, data were available for 40 patients at
      baseline and 38 patients at 1 year after HSCT (one patient died, one withdrew).
      At 1 year after HSCT, 3-month steroid-free clinical remission was seen in 13
      (38%, 95% CI 22-55) of 34 patients with available data for the whole year.
      Complete endoscopic healting was noted in 19 (50%, 34-66) of 38 patients. On
      multivariate analyses, factors associated with the primary outcome were short
      disease duration (odds ratio [OR] 0.64, 95% CI 0.41-0.997 per year; p=0.048) and
      low baseline CDAI (0.82, 0.74-0.98 per 10 units; p=0.031). 76 serious adverse
      events occurred in 23 of 40 patients with available data. The most common serious
      adverse event was infection, most of which were treatment related. Smoking and
      perianal disease at baseline were independent factors associated with the number
      of serious adverse events (OR 3.07 [95% CI 1.75-5.38; p=0.0001] for smoking and
      3.97 [2.17-7.25; p<0.0001] for perianal disease) on multivariate analysis.
      INTERPRETATION: When assessed using endpoints traditional for clinical trials of
      conventional therapy in Crohn's disease, HSCT resulted in clinical and endoscopic
      benefit, although it was associated with a high burden of adverse events. The
      prognostic factors identified could allow the therapy to be targeted to patients
      most likely to benefit and not experience serious adverse events. FUNDING: Broad
      Medical Research Program, National Institute for Health Research Senior
      Investigator Award, The University of Nottingham Medical School Dean's Fund, and
      The Nottingham University Hospitals NHS Trust Research and Development Fund.

PMID- 28497756
TI  - S-1 versus placebo in patients with sorafenib-refractory advanced hepatocellular
      carcinoma (S-CUBE): a randomised, double-blind, multicentre, phase 3 trial.
AB  - BACKGROUND: Unresectable advanced hepatocellular carcinoma is a heterogeneous
      disease, for which sorafenib is the first targeted agent approved for first-line
      therapy, and treatment options for patients with sorafenib-refractory advanced
      hepatocellular carcinoma are limited. We assessed the efficacy and safety of S-1,
      a chemotherapeutic agent based on fluorouracil, in patients with sorafenib
      refractory advanced hepatocellular carcinoma. METHODS: We did a randomised,
      double-blind, placebo-controlled, phase 3 study done at 57 sites in Japan.
      Patients with advanced hepatocellular carcinoma who were ineligible for surgical
      or local-regional therapy and judged refractory to sorafenib (ie, had progressed
      on sorafenib or had discontinued sorafenib because of adverse events) were
      randomly assigned (2:1) to receive oral S-1 (weight-banded 80 mg/m2 [80-120 mg
      per day]), or placebo, twice per day for 28 days consecutively, followed by a
      minimum 14 day drug-free period. This cycle was repeated until disease
      progression or the patient became intolerant to the study treatment. Patients
      were stratified by site and presence or absence of extrahepatic metastasis or
      vascular invasion. The primary endpoint was overall survival, assessed in the
      full analysis set (ie, all patients who were treated with study drug except any
      individuals who were found not to have hepatocellular carcinoma or who were found
      to have active double cancer). Patients, medical staff, investigators, and the
      sponsor were masked to treatment assignment. Blinding was maintained even after
      study treatment concluded. This study is registered with JapicCTI, number
      JapicCTI-090920, and has been completed. FINDINGS: Between Oct 26, 2009, and Aug
      22, 2012, we screened 399 patients. 65 patients were excluded due to not meeting
      criteria (n=61), declining to participate (n=3), or other reasons (n=1). 334
      patients were randomly assigned to receive either S-1 (n=223) or placebo (n=111).
      One patient in the S-1 group did not receive treatment, and was thus excluded
      from analyses. At data cutoff, median follow-up was 32.4 months (IQR 24.0-34.7)
      in the S-1 group and 32.9 months (23.7-39.5) in the placebo group. Median overall
      survival was 11.1 months (95% CI 9.7-13.1) in the S-1 group and 11.2 months (9.2
      12.8) in the placebo group (hazard ratio 0.86, 95% CI 0.67-1.10; p=0.220). The
      most frequently reported adverse events were skin hyperpigmentation (123 [55%] of
      222 patients in the S-1 group vs nine [8%] of 111 patients in the placebo group),
      decreased appetite (104 [47%] vs 21 [19%]), fatigue (102 [46%] vs 20 [18%]),
      diarrhoea (77 [35%] vs 14 [13%]), and increased blood bilirubin (77 [35%] vs 14
      [13%]). Serious adverse events were reported in 90 (41%) of 222 patients in the S
      1 group and 24 (22%) of 111 patients in the placebo group. Five treatment-related
      deaths were reported in the S-1 group. INTERPRETATION: S-1 did not prolong
      overall survival in patients with sorafenib-refractory advanced hepatocellular
      carcinoma. Further research is needed to identify subgroups of patients who might
      benefit from S-1. FUNDING: Taiho Pharmaceuticals.

PMID- 28497757
TI  - Safety and tolerability of veliparib combined with capecitabine plus radiotherapy
      in patients with locally advanced rectal cancer: a phase 1b study.
AB  - BACKGROUND: Further optimisation of present standard chemoradiation is needed in
      patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose)
      polymerase inhibitor, has been shown to enhance the antitumour activity of
      chemotherapy and radiotherapy in preclinical models. We aimed to establish the
      maximum tolerated dose and establish the recommended phase 2 dose of veliparib
      combined with neoadjuvant capecitabine and radiotherapy. METHODS: This phase 1b,
      open-label, multicentre, dose-escalation study was done at six hospitals (one in
      Australia and five in the USA). Patients were eligible if they were aged 18 years
      or more and were newly diagnosed with stage II to III locally advanced,
      resectable adenocarcinoma of the rectum with a distal tumour border of less than
      12 cm from anal verge. Patients were ineligible if they had received anticancer
      therapy or surgery (except colostomy or ileostomy) 28 days or less before the
      first dose of study drug, previous pelvic radiotherapy, or previous treatment
      with poly (ADP-ribose) polymerase inhibitors. Enrolled patients received
      capecitabine (825 mg/m2 orally twice daily) with radiotherapy (50.4 Gy in 1.8 Gy
      fractions daily, approximately 5 days consecutively per week for about 5.5
      weeks). Veliparib (20-400 mg orally twice daily) was administered daily starting
      on day 2 of week 1 and continuing until 2 days after radiotherapy completion.
      Patients underwent total mesorectal excision 5-10 weeks after radiotherapy
      completion. The primary objectives were to establish the maximum tolerated dose
      and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy,
      with an exposure-adjusted continual reassessment methodology. Efficacy and safety
      analyses were done per protocol. The reported study has completed accrual and all
      analyses are final. This trial is registered with ClinicalTrials.gov, number
      NCT01589419. FINDINGS: Between June 12, 2012, and Jan 13, 2015, 32 patients
      received veliparib (22 in the dose-escalation group; ten in the safety expansion
      group); 31 were assessable for efficacy (<400 mg, n=16; 400 mg, n=15). During
      dose escalation, grade 2 dose-limiting toxic effects occurred in two patients; no
      grade 3-4 dose-limiting toxic effects were noted. Therefore, the maximum
      tolerated dose was not reached; the recommended phase 2 dose was selected as 400
      mg twice daily. The most common treatment-emergent adverse events in all 32
      patients were nausea (17 [53%]), diarrhoea (16 [50%]), and fatigue (16 [50%]).
      Grade 3 diarrhoea was noted in three (9%) of 32 patients; no grade 4 events were
      reported. Veliparib pharmacokinetics were dose proportional, with no effect on
      capecitabine pharmacokinetics. Tumour downstaging after surgery was noted in 22
      (71%) of 31 patients; nine (29%) of 31 patients achieved a pathological complete
      response. INTERPRETATION: Veliparib plus capecitabine and radiotherapy had an
      acceptable safety profile and showed a dose-proportional pharmacokinetic profile
      with no effect on the pharmacokinetics of capecitabine. Preliminary antitumour
      activity warrants further evaluation. FUNDING: AbbVie Inc.

PMID- 28497759
TI  - Long-term challenges and perspectives of pre-adolescent liver disease.
AB  - Chronic liver disease is a growing problem that has substantial effects on public
      health. Many paediatric liver conditions are precursors of adult chronic liver
      disease, cirrhosis, and hepatocellular carcinoma. Clinical management of Wilson's
      disease, autoimmune liver disease, and chronic biliary disorders, such as biliary
      atresia, which remains the most common paediatric chronic liver disease and
      indication for liver transplantation, is similar in children and adults. In the
      past 10 or so years, paediatric hepatology has expanded into neighbouring
      clinical areas, such as metabolic liver diseases and systemic conditions with
      liver involvement. We aim to describe some of these disorders, and outline their
      natural history and possible differences between management in adults and
      children to stimulate further debate on the optimal transition of care between
      paediatric and adult specialists.

PMID- 28497760
TI  - The intestinal microbiome and paediatric liver disease.
AB  - The intestinal microbiome has been the intense focus of recent study, but how the
      microbiota affects connected organs, such as the liver, has not been fully
      elucidated. The microbiome regulates intestinal permeability and helps to
      metabolise the human diet into small molecules, thus directly affecting liver
      health. Several studies have linked intestinal dysbiosis to the severity and
      progression of liver diseases, such as non-alcoholic fatty liver disease, non
      alcoholic steatohepatitis, primary sclerosing cholangitis, total parenteral
      nutrition-associated liver disease, and cystic fibrosis-associated liver disease.
      However, there is limited information and interpretation with regard to how the
      microbiome could contribute to liver disease in the paediatric population.
      Notably, the gut microbiota is distinct at birth and does not establish an adult
      profile until the third year of life. Clinical research suggests that paediatric
      liver disease differs in both severity and rate of progression compared with
      adult forms, suggesting independent mechanisms of pathogenesis. We discuss data
      linking the intestinal microbiome to liver disease development and therapeutic
      efforts to modify the microbiome in children.

PMID- 28497762
TI  - Correction to Lancet Gastroenterol Hepatol 2017; 2: 427-34.

PMID- 28497761
TI  - Beyond the Milan criteria for liver transplantation in children with hepatic
      tumours.
AB  - The Milan criteria were originally defined in the context of adult liver
      transplantation for patients with hepatocellular carcinoma and cirrhotic livers.
      The aim of the criteria was to select patients with small tumours and no disease
      spread who had a good chance of success, thus avoiding futile transplants. This
      objective was reached successfully. For the management of selected children with
      unresectable hepatoblastoma, an almost opposite strategy was proposed and has
      been implemented in the past two decades, in which transplantation is indicated
      on the basis of large tumour size and anatomy that precludes the possibility of
      safe and radical resection. This approach has also had great success. Although
      both strategies are well established for these two different age groups and
      diseases, a grey area exists with regard to hepatocellular carcinoma or other
      tumour types in children. In this Viewpoint, we aim to review the existing
      literature about the indications, selection process, and results of liver
      transplantation for liver tumours in children, and discuss evidence that supports
      the implementation of either of the two strategies in the context of managing
      selected children with liver tumours using transplantation.

PMID- 28497763
TI  - [On air ambulance services[Editorial]].

PMID- 28497764
TI  - [New year marks a turning point[Editorial]].

PMID- 28497758
TI  - Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus
      ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with
      cirrhosis (ABACUS): a prospective observational study.
AB  - BACKGROUND: We ran a compassionate use nationwide programme (ABACUS) to provide
      access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin
      for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir,
      and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with
      cirrhosis at high risk of decompensation while approval of these regimens was
      pending in Italy. METHODS: In this prospective observational study, we collected
      data from a compassionate use nationwide programme from March 17, 2014, to May
      28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of
      decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg),
      and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks
      (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype
      1a infection). Patients with HCV genotype 4 infection were given coformulated
      ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day
      for 24 weeks. All patients were given weight-based ribavirin. The primary
      efficacy endpoint was sustained virological response at week 12 after the end of
      treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate
      logistic regression analyses were used to identify baseline characteristics
      associated with SVR12. Adverse events were recorded throughout the study.
      FINDINGS: 728 (96%) of 762 patients with cirrhosis who were given ombitasvir,
      paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy
      for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that
      bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds
      ratio [OR] 4.76 [95% CI 1.83-12.3]; p=0.001). 166 (23%) of 734 patients included
      in safety analyses had an adverse event. 25 (3%) patients discontinued treatment
      because of adverse events. Asthenia was the most commonly reported adverse event,
      occurring in 36 (5%) patients. INTERPRETATION: Our findings suggest that the
      safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or
      without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection
      and cirrhosis at high risk of decompensation in a real-life setting are similar
      to those reported in clinical trials. The concordance with clinical trials
      provides reassurance that the reported efficacy of this treatment in clinical
      trials will translate to its use in routine clinical practice. FUNDING:
      Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di
      Palermo.

PMID- 28497765
TI  - [Acute myocardial infarction among Icelanders forty years old and younger 2005
      2009. Comparison with a study carried out 1980-1984].
AB  - INTRODUCTION: While acute myocardial infarction  (AMI) mostly is a disease of the
      elderly it also affects younger individuals, often with serious consequenses. In
      1980-1984 a study was carried out on the incidence, risk factors, infarct
      location and distribution of atherosclerosis among Icelanders forty years and
      younger with AMI. Here we present the results of a similar study carried out for
      the five year period 2005-2009. MATERIALS AND METHODS: Medical and autopsy
      records of all individuals, forty years and younger, diagnosed with AMI (I21 in
      ICD-10) at Landspitali, National University Hospital 2005-2009, or suffering
      sudden cardiac death in Iceland during the same period were reviewed. Blood
      tests, electrocardiograms, echocardiograms, coronary angiograms and autopsy
      results were reviewed with respect to AMI-criteria. Statistical comparisons of
      ratios and means were carried out using Chi-square test and T-test, respectively.
      RESULTS: 38 individuals 40 years and younger, 32 males and 6 females, fulfilled
      the diagnostic criteria of AMI. Calculated incidence for the population at risk
      was 10/100.000/year (14/100.000/year in 1980-1984) and the mean age +/-S.D. was
      36.7+/-3.9. Three (7.9%) died suddenly before reaching hospital but of the 35
      hospitalised patients 30 day mortality was zero, compared to nine (23.7%) pre
      hospital deaths and two (6.9%) hospital deaths in 1980-1984. Thus, combined pre
      hospital and in-hospital (30 day) mortality was 28.9% and 7.9% in the previous
      and recent time periods, respectively (p=0.02). In 2005-2009, 77.1% had a smoking
      history and 31.4% were hypertensive compared to 97% and 6.9% in 1980-85 (p=0.026
      and p=0.015, respectively). Body mass index (BMI) was higher in the later period,
      28.6+/-4,8 kg/m2 compared to 26.1+/-3.6 (mean+/-S.D.; p=0.04) but s-cholesterol
      was lower, 5.1+/-1.4 mmol/L compared to 6.3+/-1.16 ( mean+/-S.D.; p<0.01). In
      both studies single coronary artery disease was the most common angiographic
      pattern and the left anterior descending artery most often involved. CONCLUSION:
      Our results show that in two surveys 25 years apart AMI patients 40 years and
      younger are most often men. Smoking and family history were the most prominent
      risk factors during both periods but hypertension and high BMI were more common
      in 2005-2009 than in 1980-1984. Prognosis, as indicated by combined pre-hospital
      and in-hospital (30 day) mortality has improved. Key words: Myocardial
      infarction, forty and younger, incidence, risk factors, mortality, time trend
      Correspondence: Gudmundur Thorgeirsson gudmth@landspitali.is.

PMID- 28497766
TI  - [MRI for diagnosis of low back pain: Usability, association with symptoms and
      influence on treatment].
AB  - BACKGROUND: Non-specific low-back pain is a worldwide problem. More specific
      diagnosis could improve prognosis. Magnetic resonance imaging (MRI) became
      available in Akureyri Hospital in 2004 but its utilisation in diagnosing low-back
      pain has not been investigated. OBJECTIVE: To study the use of MRI in diagnosing
      low-back pain, correlation of the MRI outcomes with other clinical findings and
      its possible effects on treatment. METHODS: Retrospective, descriptive analysis
      of patients' journals. Included were all adult (18 years and older) residents of
      Akureyri who underwent low-back MRI in Akureyri Hospital in 2009. RESULTS: During
      2009, 159 patients (82 women) underwent low-back MRI, mean age 51 years (18-88).
      The most common pathological findings were connected to the lumbar disk. Disk
      herniation was diagnosed in 38% of the patients, 77% at the L4-L5 or L5-S1 level.
      MRI results correlated poorly with symptoms and clinical findings. Treatment
      options for disk herniation were prescription of medications (70%), referrals to
      physiotherapy (67%) and orthopaedic surgeons (61%). Nine patients were operated.
      Among patients referred to physiotherapy, 49% were first examined with MRI and
      thus waited longer for referral than those referred directly to physiotherapy
      (p=0.008). One year after the MRI, recovery rate was 51%. Prognosis was better
      for patients referred to physiotherapy (p=0.024). CONCLUSIONS: MRI seems to be
      used for general diagnosis of low-back pain. Symptoms and MRI results correlate
      poorly, emphasizing the need for the doctor's thorough weighing of clinical and
      MRI findings when diagnosing low-back pain. Recovery rate of patients with lumbar
      disk herniation improves by physiotherapy. The general use of MRI might delay
      treatment. Key words: Magnetic resonance imaging, clinical diagnosis, low-back
      pain, lumbar disk herniation, treatment, physiotherapy. Correspondence: Gunnar
      Svanbergsson gsvanbergs@gmail.com.

PMID- 28497767
TI  - [Evaluation of a thyroid nodule].
AB  - Thyroid nodules are common and their incidence has increased due to various
      factors. Systematic approach to the work-up of thyroid nodules is necessary to
      decrease overdiagnosis as well as over treatment. Applying the trifecta of
      history, physicial examination and high-resolution ultrasound (HRUS) as well as
      fine needle aspiration biopsy (FNAB) with added TSH measurement is important in
      the work-up. HRUS is a central part in the diagnostic approach, being able to
      risk classify nodules and selecting nodules for FNAB. Systematic analysis of
      aspirates is necessary to simplify communication between cytologists and
      clinicians. 1Department of Otolaryngology - Head and Neck Surgery, Landspitali,
      Fossvogi, 2Department of Medicine, University of Iceland. Key words: thyroid
      nodule, thyroid cancer, ultrasound, cytology Correspondence: Geir Tryggvason,
      geirt@lsh.is.

PMID- 28497768
TI  - Antibacterial effects of antiretrovirals, potential implications for microbiome
      studies in HIV.
AB  - BACKGROUND: Despite being used by more than 18 million people our understanding
      of the extent of the effects of antiretrovirals on the human body and other
      organisms remains incomplete. In addition, the direct effect of antiretrovirals
      on the gut microbiota of HIV-infected individuals has been largely overlooked in
      microbiome studies concerned with HIV-infected individuals. METHODS: Here we
      tested 25 antiretrovirals on Bacillus subtilis and Escherichia coli using a broth
      microdilution assay to assess whether these drugs have an antibacterial effect.
      RESULTS: We found that several widely used antiretroviral drugs have in vitro
      antibacterial activity against both gram-positive and gram-negative commensal
      bacteria. Efavirenz inhibited the growth of B. subtilis with a minimum inhibitory
      concentration (MIC) of 16 ug/ml (in all three replicates), while 2',3'
      dideoxyinosine and zidovudine inhibited the growth of E. coli with an MIC of 16
      32 ug/ml and 0.016-0.125 ug/ml (respectively). CONCLUSIONS: Given the large and
      increasing number of individuals on antiretrovirals, and the lifelong nature of
      HIV treatment, this proof-of-concept report could have several potential
      implications, including an impact of antiretrovirals on bacterial coinfections,
      as well as potentials for drug discovery and repositioning.

PMID- 28497769
TI  - Automated EEG artifact elimination by applying machine learning algorithms to ICA
      based features.
AB  - OBJECTIVE: Biological and non-biological artifacts cause severe problems when
      dealing with electroencephalogram (EEG) recordings. Independent component
      analysis (ICA) is a widely used method for eliminating various artifacts from
      recordings. However, evaluating and classifying the calculated independent
      components (IC) as artifact or EEG is not fully automated at present. APPROACH:
      In this study, we propose a new approach for automated artifact elimination,
      which applies machine learning algorithms to ICA-based features. MAIN RESULTS: We
      compared the performance of our classifiers with the visual classification
      results given by experts. The best result with an accuracy rate of 95% was
      achieved using features obtained by range filtering of the topoplots and IC power
      spectra combined with an artificial neural network. SIGNIFICANCE: Compared with
      the existing automated solutions, our proposed method is not limited to specific
      types of artifacts, electrode configurations, or number of EEG channels. The main
      advantages of the proposed method is that it provides an automatic, reliable,
      real-time capable, and practical tool, which avoids the need for the time
      consuming manual selection of ICs during artifact removal.

PMID- 28497770
TI  - Anomalous charge transport in reduced graphene oxide films on a uniaxially
      strained elastic substrate.
AB  - We investigate temperature-dependent charge transport in reduced graphene oxide
      (rGO) films coated on flexible polydimethylsiloxane (PDMS) substrates which are
      subject to uniaxial strain. Variable strain, up to 10%, results in an anisotropic
      morphology comprising of quasi-periodic linear array of deformations which are
      oriented perpendicular to the direction of strain. The anisotropy is reflected in
      the charge transport measurements, when conduction in the direction parallel and
      perpendicular to the applied strain are compared. Temperature dependence of
      resistance is measured for different values of strain in the temperature interval
      80-300 K. While the resistance increases significantly upon application of
      strain, the temperature-dependent response shows anomalous decrease in resistance
      ratio R 80 K/R 300 K upon application of strain. This observation of favorable
      conduction processes under strain is further corroborated by reduced activation
      energy analysis of the temperature-dependent transport data. These anomalous
      transport features can be reconciled based on mutually competing effects of two
      processes: (i) thinning of graphene at the sites of periodic deformations, which
      tends to enhance the overall resistance by a purely geometrical effect, and (ii)
      locally enhanced inter-flake coupling in these same regions which contributes to
      improved temperature-dependent conduction.

PMID- 28497771
TI  - An isometric muscle force estimation framework based on a high-density surface
      EMG array and an NMF algorithm.
AB  - OBJECTIVE: To realize accurate muscle force estimation, a novel framework is
      proposed in this paper which can extract the input of the prediction model from
      the appropriate activation area of the skeletal muscle. APPROACH: Surface
      electromyographic (sEMG) signals from the biceps brachii muscle during isometric
      elbow flexion were collected with a high-density (HD) electrode grid (128
      channels) and the external force at three contraction levels was measured at the
      wrist synchronously. The sEMG envelope matrix was factorized into a matrix of
      basis vectors with each column representing an activation pattern and a matrix of
      time-varying coefficients by a nonnegative matrix factorization (NMF) algorithm.
      The activation pattern with the highest activation intensity, which was defined
      as the sum of the absolute values of the time-varying coefficient curve, was
      considered as the major activation pattern, and its channels with high weighting
      factors were selected to extract the input activation signal of a force
      estimation model based on the polynomial fitting technique. MAIN RESULTS:
      Compared with conventional methods using the whole channels of the grid, the
      proposed method could significantly improve the quality of force estimation and
      reduce the electrode number. SIGNIFICANCE: The proposed method provides a way to
      find proper electrode placement for force estimation, which can be further
      employed in muscle heterogeneity analysis, myoelectric prostheses and the control
      of exoskeleton devices.

PMID- 28497772
TI  - Surface-rough Fe-N/C composite wrapped on carbon nanotubes as efficient
      electrocatalyst for oxygen reduction reaction.
AB  - Fe-N/C composites are considered one of the most promising non-precious-metal
      electrocatalysts for oxygen reduction reaction (ORR). In this paper, we fabricate
      a novel and efficient carbon nanotube (CNT)-supported Fe-N/C composite catalyst,
      via the surface-self-polymerization of polydopamine and then the incorporation
      with Fe species on CNTs, followed by the pyrolysis process. The obtained catalyst
      demonstrates excellent electrocatalytic performance towards ORR in alkaline
      media. The modification of Fe-incorporated nitrogen-rich-carbons (Fe-CNx) on CNTs
      lowers the ORR half-wave-potential by ~190 mV, giving this catalyst with an onset
      ORR potential of 0.95 V (versus reversible hydrogen electrode (RHE)), a half-wave
      potential of 0.82 V (versus RHE), and the limiting current density of 5.39 mA cm
      2 in 0.1 M KOH. The performance of the as-prepared catalyst is comparatively
      better than the commercially available Pt/C in terms of positive half-wave
      potential and larger limiting current, superior durability, and higher tolerance
      to the methanol.

PMID- 28497773
TI  - Re-evaluation of the steady-state self-quenching constant of quinine bisulphate
      from fluorescence measurements in transmission geometry.
AB  - In the present work we show that a recent methodology developed by us to acquire
      emission spectra and fluorescence quantum yields of highly absorbing samples in
      transmission configuration, constitutes a very simple and robust alternative to
      determine self-quenching constants, K SQ. We measured the absorption and the
      steady-state emission spectra of quinine bisulphate, QBS, solutions ranging
      between 1.5 * 10-5 and 1.5 * 10-1 M. From these data, we calculated the expected
      emission spectra, affected by re-absorption, for all QBS concentrations. For
      higher concentrations, the re-absorption in the excitation/detection direction
      reaches values up to 6% of the total emitted intensity. The K SQ of the dye was
      re-evaluated from the concentration dependence of the quotients between the
      calculated and the experimental integrated emission spectra. The obtained value,
      K SQ = 18.4 +/- 0.1 M-1, shows no significant differences with those obtained
      from steady-state and average lifetimes by other authors, pointing out the
      diffusional nature of the self-quenching phenomenon. The present work helps
      clarify some ambiguous aspects concerning the photophysics of QBS, stressing that
      re-absorption phenomena must be considered in QBS concentrated solutions for
      accuracy measurements.

PMID- 28497774
TI  - Evaluation of respiratory- and postural-induced changes on the ballistocardiogram
      signal by time warping averaging.
AB  - OBJECTIVE: The aim of this work was to evaluate the potential changes in the
      ballistocardiogram (BCG) signal induced by different respiratory patterns and
      posture, by using the dynamic time warping (DTW) technique. APPROACH: BCG signals
      were recorded in a group of 20 healthy volunteers, simultaneously with an
      electrocardiogram (ECG). Two recordings, one in a supine (SUP) and one in a
      standing (ST) position, including spontaneous breathing, two 1 min apneas (at
      full and empty-lungs, respectively) and 30 s of Valsalva, were analyzed. A warped
      averaged waveform was computed for each phase, from which amplitude and temporal
      parameters were extracted to characterize each condition. MAIN RESULTS:
      Variations were found in both amplitude and duration of BCG-derived parameters
      among manoeuvres, especially when compared to spontaneous breathing, suggesting a
      complex interaction between intra-thoracic pressure changes acting on venous
      return, together with the autonomic nervous system modulation on heart rate. The
      effect of a hydrostatic pressure gradient elicited by postural conditions was
      also evident. SIGNIFICANCE: Posture and respiratory manoeuvres affect the BCG
      signal in different ways, probably as a result of changes induced in preload and
      afterload. This supports the need to define separate normality ranges for each
      posture and/or breathing conditions, as well as the importance of applying
      specific manoeuvres to highlight any pathological response in the computed BCG
      parameters.

PMID- 28497775
TI  - Optical evidence for the spin-state disorder in LaCo1-x Rh x O3.
AB  - We have measured the infrared reflectivity of single-crystalline samples of LaCo1
      x Rh x O3 (x  =  0, 0.05 and 0.10) from 10 to 300 K from 0.05 to 0.15 eV. We find
      that the optical phonons of the Co-O stretching mode depend on temperature and
      the Rh content. Analysis with three Lorentz oscillators reveals that the spin
      state of Co3+ in LaCo1-x Rh x O3 can be understood in terms of a solid solution
      of low-spin- and high-spin-state Co3+ ions, and the substituted Rh ion retains
      some fraction of the high-spin Co3+ ions down to low temperature.

PMID- 28497776
TI  - Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS
      tetrapods.
AB  - Semiconductor nanostructures capable of emitting from two excited states and
      thereby of producing two photoluminescence colours are of fundamental and
      potential technological significance. In this limited class of nanocrystals,
      CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and
      green) multiexcitonic emission, with green emission from the CdS arms emerging
      only at high excitation fluences. Here we show that by synthetic shape-tuning,
      both this multi-colour emission process, and blinking and photobleaching
      behaviours of single tetrapods can be controlled. Specifically, we find that the
      properties of dual emission and single-nanostructure photostability depend on
      different structural parameters-arm length and arm diameter, respectively-but
      that both properties can be realized in the same nanostructure. Furthermore,
      based on results of correlated photoluminescence and transient absorption
      measurements, we conclude that hole-trap filling in the arms and partial state
      filling in the core are necessary preconditions for the observation of
      multiexciton multi-colour emission.

PMID- 28497777
TI  - Phase I/II clinical trial to assess safety and efficacy of intratumoral and
      subcutaneous injection of HVJ-E in castration-resistant prostate cancer patients.
AB  - Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ
      E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell
      surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo.
      HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and
      cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an
      open-label, single-arm, phase I/II clinical trial in patients with castration
      resistant prostate cancer (CRPC) to determine the safety and efficacy of
      intratumoral and subcutaneous injection of HVJ-E. Patients with CRPC who were
      docetaxel-resistant or could not receive docetaxel treatment were eligible. HVJ-E
      was injected directly into the prostate on day 1 and subcutaneously on days 5, 8
      and 12 in two 28-day treatment cycles using a 3+3 dose-escalation design. The
      primary end points were to evaluate safety and tolerability of HVJ-E. The
      secondary end points were to analyze tumor immunity and antitumor effect. The
      study is registered at UMIN Clinical Trials Registry, number UMIN000006142. Seven
      patients were enrolled, and six patients received HVJ-E. Grade 2 or 3 adverse
      events (Common Terminology Criteria for Adverse Events Ver. 4.0) were urinary
      retention and lymphopenia from which the patients recovered spontaneously. No
      Grade 4 adverse events were observed. Radiographically, three patients had stable
      disease in the low-dose group, and one patient had stable disease and two had
      progressive disease in the high-dose group. The prostate-specific antigen (PSA)
      declined from 14 to 1.9 ng ml-1 in one patient in the low-dose group after two
      cycles of HVJ-E treatment, and the PSA response rate was 16.6%. NK cell activity
      was elevated from day 12 to day 28 after HVJ-E administration, whereas serum
      interleukin-6, interferon (IFN)-alpha, IFN-beta and IFN-gamma levels were not
      affected by HVJ-E treatment. Intratumoral and subcutaneous injections of HVJ-E
      are feasible and PSA response was observed in a subgroup of CRPC patients.

PMID- 28497778
TI  - PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of
      DAXX and histone H3.3.
AB  - Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions
      and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog)
      are frequent events and are associated with therapeutic resistance. Herein, we
      report a novel chromatin-associated function of PTEN in complex with the histone
      chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with
      DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX
      H3.3 association on the chromatin, independently of PTEN enzymatic activity.
      Furthermore, DAXX inhibition specifically suppresses tumour growth and improves
      the survival of orthotopically engrafted mice implanted with human PTEN-deficient
      glioma samples, associated with global H3.3 genomic distribution changes leading
      to upregulation of tumour suppressor genes and downregulation of oncogenes.
      Moreover, DAXX expression anti-correlates with PTEN expression in GBM patient
      samples. Since loss of chromosome 10 and PTEN are common events in cancer, this
      synthetic growth defect mediated by DAXX suppression represents a therapeutic
      opportunity to inhibit tumorigenesis specifically in the context of PTEN
      deletion.

PMID- 28497780
TI  - Giant five-photon absorption from multidimensional core-shell halide perovskite
      colloidal nanocrystals.
AB  - Multiphoton absorption processes enable many technologically important
      applications, such as in vivo imaging, photodynamic therapy and optical limiting,
      and so on. Specifically, higher-order nonlinear absorption such as five-photon
      absorption offers significant advantages of greater spatial confinement,
      increased penetration depth, reduced autofluorescence, enhanced sensitivity and
      improved resolution over lower orders in bioimaging. Organic chromophores and
      conventional semiconductor nanocrystals are leaders in two-/three-photon
      absorption applications, but face considerable challenges from their small five
      photon action cross-sections. Herein, we reveal that the family of halide
      perovskite colloidal nanocrystals transcend these constraints with highly
      efficient five-photon-excited upconversion fluorescence-unprecedented for
      semiconductor nanocrystals. Amazingly, their multidimensional type I (both
      conduction and valence band edges of core lie within bandgap of shell) core-shell
      (three-dimensional methylammonium lead bromide/two-dimensional octylammonium lead
      bromide) perovskite nanocrystals exhibit five-photon action cross-sections that
      are at least 9 orders larger than state-of-the-art specially designed organic
      molecules. Importantly, this family of halide perovskite nanocrystals may enable
      fresh approaches for next-generation multiphoton imaging applications.

PMID- 28497779
TI  - L-selectin mechanochemistry restricts neutrophil priming in vivo.
AB  - Circulating neutrophils must avoid premature activation to prevent tissue injury.
      The leukocyte adhesion receptor L-selectin forms bonds with P-selectin
      glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node
      addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen
      (catch) or weaken (slip) bonds between biological molecules. How these
      mechanochemical processes influence function in vivo is unexplored. Here we show
      that mice expressing an L-selectin mutant (N138G) have altered catch bonds and
      prolonged bond lifetimes at low forces. Basal lymphocyte homing and neutrophil
      recruitment to inflamed sites are normal. However, circulating neutrophils form
      unstable aggregates and are unexpectedly primed to respond robustly to
      inflammatory mediators. Priming requires signals transduced through L-selectin
      N138G after it engages PSGL-1 or PNAd. Priming enhances bacterial clearance but
      increases inflammatory injury and enlarges venous thrombi. Thus, L-selectin
      mechanochemistry limits premature activation of neutrophils. Our results
      highlight the importance of probing how mechanochemistry functions in vivo.

PMID- 28497781
TI  - Face classification using electronic synapses.
AB  - Conventional hardware platforms consume huge amount of energy for cognitive
      learning due to the data movement between the processor and the off-chip memory.
      Brain-inspired device technologies using analogue weight storage allow to
      complete cognitive tasks more efficiently. Here we present an analogue non
      volatile resistive memory (an electronic synapse) with foundry friendly
      materials. The device shows bidirectional continuous weight modulation behaviour.
      Grey-scale face classification is experimentally demonstrated using an integrated
      1024-cell array with parallel online training. The energy consumption within the
      analogue synapses for each iteration is 1,000 * (20 *) lower compared to an
      implementation using Intel Xeon Phi processor with off-chip memory (with
      hypothetical on-chip digital resistive random access memory). The accuracy on
      test sets is close to the result using a central processing unit. These
      experimental results consolidate the feasibility of analogue synaptic array and
      pave the way toward building an energy efficient and large-scale neuromorphic
      system.

PMID- 28497782
TI  - RAF proteins exert both specific and compensatory functions during tumour
      progression of NRAS-driven melanoma.
AB  - NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically,
      CRAF but not BRAF was shown to be critical for various RAS-driven cancers,
      raising the question of the role of RAF proteins in NRAS-induced melanoma. Here,
      using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we
      investigate their contribution in tumour progression, from the onset of benign
      tumours to malignant tumour maintenance. We show that BRAF expression is required
      for ERK activation and nevi development, demonstrating a critical role in the
      early stages of NRAS-driven melanoma. After melanoma formation, single Braf or
      Craf ablation is not sufficient to block tumour growth, showing redundant
      functions for RAF kinases. Finally, proliferation of resistant cells emerging in
      the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation.
      These results reveal specific and compensatory functions for BRAF and CRAF and
      highlight an addiction to RAF signalling in NRAS-driven melanoma.

PMID- 28497784
TI  - An integrated parity-time symmetric wavelength-tunable single-mode microring
      laser.
AB  - Mode control in a laser cavity is critical for a stable single-mode operation of
      a ring laser. In this study we propose and experimentally demonstrate an
      electrically pumped parity-time (PT)-symmetric microring laser with precise mode
      control, to achieve wavelength-tunable single-mode lasing with an improved mode
      suppression ratio. The proposed PT-symmetric laser is implemented based on a
      photonic integrated circuit consisting of two mutually coupled active microring
      resonators. By incorporating multiple semiconductor optical amplifiers in the
      microring resonators, the PT-symmetry condition can be achieved by a precise
      manipulation of the interplay between the gain and loss in the two microring
      resonators, and the incorporation of phase modulators in the microring resonators
      enables continuous wavelength tuning. Single-mode lasing at 1,554.148 nm with a
      sidemode suppression ratio exceeding 36 dB is demonstrated and the lasing
      wavelength is continuously tunable from 1,553.800 to 1,554.020 nm.

PMID- 28497783
TI  - BLISS is a versatile and quantitative method for genome-wide profiling of DNA
      double-strand breaks.
AB  - Precisely measuring the location and frequency of DNA double-strand breaks (DSBs)
      along the genome is instrumental to understanding genomic fragility, but current
      methods are limited in versatility, sensitivity or practicality. Here we present
      Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1)
      direct labelling of DSBs in fixed cells or tissue sections on a solid surface;
      (2) low-input requirement by linear amplification of tagged DSBs by in vitro
      transcription; (3) quantification of DSBs through unique molecular identifiers;
      and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous
      and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and
      liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome
      wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9
      and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results
      establish BLISS as a versatile, sensitive and efficient method for genome-wide
      DSB mapping in many applications.

PMID- 28497785
TI  - Charcoal evidence that rising atmospheric oxygen terminated Early Jurassic ocean
      anoxia.
AB  - The Toarcian Oceanic Anoxic Event (T-OAE) was characterized by a major
      disturbance to the global carbon(C)-cycle, and depleted oxygen in Earth's oceans
      resulting in marine mass extinction. Numerical models predict that increased
      organic carbon burial should drive a rise in atmospheric oxygen (pO2) leading to
      termination of an OAE after ~1 Myr. Wildfire is highly responsive to changes in
      pO2 implying that fire-activity should vary across OAEs. Here we test this
      hypothesis by tracing variations in the abundance of fossil charcoal across the T
      OAE. We report a sustained ~800 kyr enhancement of fire-activity beginning ~1 Myr
      after the onset of the T-OAE and peaking during its termination. This major
      enhancement of fire occurred across the timescale of predicted pO2 variations,
      and we argue this was primarily driven by increased pO2. Our study provides the
      first fossil-based evidence suggesting that fire-feedbacks to rising pO2 may have
      aided in terminating the T-OAE.

PMID- 28497786
TI  - Tunable and low-loss correlated plasmons in Mott-like insulating oxides.
AB  - Plasmonics has attracted tremendous interests for its ability to confine light
      into subwavelength dimensions, creating novel devices with unprecedented
      functionalities. New plasmonic materials are actively being searched, especially
      those with tunable plasmons and low loss in the visible-ultraviolet range. Such
      plasmons commonly occur in metals, but many metals have high plasmonic loss in
      the optical range, a main issue in current plasmonic research. Here, we discover
      an anomalous form of tunable correlated plasmons in a Mott-like insulating oxide
      from the Sr1-xNb1-yO3+delta family. These correlated plasmons have multiple
      plasmon frequencies and low loss in the visible-ultraviolet range. Supported by
      theoretical calculations, these plasmons arise from the nanometre-spaced
      confinement of extra oxygen planes that enhances the unscreened Coulomb
      interactions among charges. The correlated plasmons are tunable: they diminish as
      extra oxygen plane density or film thickness decreases. Our results open a path
      for plasmonics research in previously untapped insulating and strongly-correlated
      materials.

PMID- 28497787
TI  - Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC.
AB  - Efforts to manipulate locus-specific histone acetylation to assess their causal
      role in gene expression and cellular and behavioural phenotypes have been impeded
      by a lack of experimental tools. The Cas9 nuclease has been adapted to target
      epigenomic modifications, but a detailed description of the parameters of such
      synthetic epigenome remodellers is still lacking. Here we describe a Cas9-based
      histone deacetylase (HDAC) and the design principles required to achieve locus
      specific histone deacetylation. We assess its range of activity and specificity,
      and analyse target gene expression in two different cell types to investigate
      cellular context-dependent effects. Our findings demonstrate that the chromatin
      environment is an important element to consider when utilizing this synthetic
      HDAC.

PMID- 28497788
TI  - Real-time atomistic observation of structural phase transformations in individual
      hafnia nanorods.
AB  - High-temperature phases of hafnium dioxide have exceptionally high dielectric
      constants and large bandgaps, but quenching them to room temperature remains a
      challenge. Scaling the bulk form to nanocrystals, while successful in stabilizing
      the tetragonal phase of isomorphous ZrO2, has produced nanorods with a twinned
      version of the room temperature monoclinic phase in HfO2. Here we use in situ
      heating in a scanning transmission electron microscope to observe the
      transformation of an HfO2 nanorod from monoclinic to tetragonal, with a
      transformation temperature suppressed by over 1000 degrees C from bulk. When the
      nanorod is annealed, we observe with atomic-scale resolution the transformation
      from twinned-monoclinic to tetragonal, starting at a twin boundary and
      propagating via coherent transformation dislocation; the nanorod is reduced to
      hafnium on cooling. Unlike the bulk displacive transition, nanoscale size
      confinement enables us to manipulate the transformation mechanism, and we observe
      discrete nucleation events and sigmoidal nucleation and growth kinetics.

PMID- 28497789
TI  - Underwater Leidenfrost nanochemistry for creation of size-tailored zinc peroxide
      cancer nanotherapeutics.
AB  - The dynamic underwater chemistry seen in nature is inspiring for the next
      generation of eco-friendly nanochemistry. In this context, green synthesis of
      size-tailored nanoparticles in a facile and scalable manner via a dynamic process
      is an interesting challenge. Simulating the volcano-induced dynamic chemistry of
      the deep ocean, here we demonstrate the Leidenfrost dynamic chemistry occurring
      in an underwater overheated confined zone as a new tool for customized creation
      of nanoclusters of zinc peroxide. The hydrodynamic nature of the phenomenon
      ensures eruption of the nanoclusters towards a much colder region, giving rise to
      growth of monodisperse, size-tailored nanoclusters. Such nanoparticles are
      investigated in terms of their cytotoxicity on suspension and adherent cells to
      prove their applicability as cancer nanotherapeutics. Our research can pave the
      way for employment of the dynamic green nanochemistry in facile, scalable
      fabrication of size-tailored nanoparticles for biomedical applications.

PMID- 28497790
TI  - Quantum vertex model for reversible classical computing.
AB  - Mappings of classical computation onto statistical mechanics models have led to
      remarkable successes in addressing some complex computational problems. However,
      such mappings display thermodynamic phase transitions that may prevent reaching
      solution even for easy problems known to be solvable in polynomial time. Here we
      map universal reversible classical computations onto a planar vertex model that
      exhibits no bulk classical thermodynamic phase transition, independent of the
      computational circuit. Within our approach the solution of the computation is
      encoded in the ground state of the vertex model and its complexity is reflected
      in the dynamics of the relaxation of the system to its ground state. We use
      thermal annealing with and without 'learning' to explore typical computational
      problems. We also construct a mapping of the vertex model into the Chimera
      architecture of the D-Wave machine, initiating an approach to reversible
      classical computation based on state-of-the-art implementations of quantum
      annealing.

PMID- 28497791
TI  - Formation of printable granular and colloidal chains through capillary effects
      and dielectrophoresis.
AB  - One-dimensional conductive particle assembly holds promise for a variety of
      practical applications, in particular for a new generation of electronic devices.
      However, synthesis of such chains with programmable shapes outside a liquid
      environment has proven difficult. Here we report a route to simply 'pull'
      flexible granular and colloidal chains out of a dispersion by combining field
      directed assembly and capillary effects. These chains are automatically
      stabilized by liquid bridges formed between adjacent particles, without the need
      for continuous energy input or special particle functionalization. They can
      further be deposited onto any surface and form desired conductive patterns,
      potentially applicable to the manufacturing of simple electronic circuits.
      Various aspects of our route, including the role of particle size and the
      voltages needed, are studied in detail. Looking towards practical applications,
      we also present the possibility of two-dimensional writing, rapid solidification
      of chains and methods to scale up chain production.

PMID- 28497792
TI  - Structural heterogeneity in the intrinsically disordered RNA polymerase II C
      terminal domain.
AB  - RNA polymerase II contains a repetitive, intrinsically disordered, C-terminal
      domain (CTD) composed of heptads of the consensus sequence YSPTSPS. The CTD is
      heavily phosphorylated and serves as a scaffold, interacting with factors
      involved in transcription initiation, elongation and termination, RNA processing
      and chromatin modification. Despite being a nexus of eukaryotic gene regulation,
      the structure of the CTD and the structural implications of phosphorylation are
      poorly understood. Here we present a biophysical and biochemical interrogation of
      the structure of the full length CTD of Drosophila melanogaster, which we
      conclude is a compact random coil. Surprisingly, we find that the repetitive CTD
      is structurally heterogeneous. Phosphorylation causes increases in radius,
      protein accessibility and stiffness, without disrupting local structural
      heterogeneity. Additionally, we show the human CTD is also structurally
      heterogeneous and able to substitute for the D. melanogaster CTD in supporting
      fly development to adulthood. This finding implicates conserved structural
      organization, not a precise array of heptad motifs, as important to CTD function.

PMID- 28497793
TI  - Image-guided genomics of phenotypically heterogeneous populations reveals
      vascular signalling during symbiotic collective cancer invasion.
AB  - Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to
      probe this heterogeneity, we developed an image-guided genomics technique termed
      spatiotemporal genomic and cellular analysis (SaGA) that allows for precise
      selection and amplification of living and rare cells. SaGA was used on
      collectively invading 3D cancer cell packs to create purified leader and follower
      cell lines. The leader cell cultures are phenotypically stable and highly
      invasive in contrast to follower cultures, which show phenotypic plasticity over
      time and minimally invade in a sheet-like pattern. Genomic and molecular
      interrogation reveals an atypical VEGF-based vasculogenesis signalling that
      facilitates recruitment of follower cells but not for leader cell motility
      itself, which instead utilizes focal adhesion kinase-fibronectin signalling.
      While leader cells provide an escape mechanism for followers, follower cells in
      turn provide leaders with increased growth and survival. These data support a
      symbiotic model of collective invasion where phenotypically distinct cell types
      cooperate to promote their escape.

PMID- 28497794
TI  - Pore configuration landscape of granular crystallization.
AB  - Uncovering grain-scale mechanisms that underlie the disorder-order transition in
      assemblies of dissipative, athermal particles is a fundamental problem with
      technological relevance. To date, the study of granular crystallization has
      mainly focussed on the symmetry of crystalline patterns while their emergence and
      growth from irregular clusters of grains remains largely unexplored. Here
      crystallization of three-dimensional packings of frictional spheres is studied at
      the grain-scale using X-ray tomography and persistent homology. The latter
      produces a map of the topological configurations of grains within static
      partially crystallized packings. Using numerical simulations, we show that
      similar maps are measured dynamically during the melting of a perfect crystal.
      This map encodes new information on the formation process of tetrahedral and
      octahedral pores, the building blocks of perfect crystals. Four key formation
      mechanisms of these pores reproduce the main changes of the map during
      crystallization and provide continuous deformation pathways representative of the
      crystallization dynamics.

PMID- 28497796
TI  - Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc
      mediated depletion of regulatory T-cells.
AB  - Interleukin-2 (IL-2) is an established therapeutic agent used for cancer
      immunotherapy. Since treatment efficacy is mediated by CD8+ and NK cell activity
      at the tumour site, considerable efforts have focused on generating variants that
      expand these subsets systemically, as exemplified by IL-2/antibody complexes and
      'superkines'. Here we describe a novel determinant of antitumour activity using
      fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc)
      region. Generation of long-lived IL-2-Fc variants in which CD25 binding is
      abolished through mutation effectively prevents unwanted activation of CD25+
      regulatory T-cells (Tregs) and results in strong expansion of CD25- cytotoxic
      subsets. Surprisingly, however, such variants are less effective than wild-type
      IL-2-Fc in mediating tumour rejection. Instead, we report that efficacy is
      crucially dependent on depletion of Tregs through Fc-mediated immune effector
      functions. Our results underpin an unexpected mechanism of action and provide
      important guidance for the development of next generation IL-2 therapeutics.

PMID- 28497797
TI  - Suppression of cognitive function in hyperthermia; From the viewpoint of
      executive and inhibitive cognitive processing.
AB  - Climate change has had a widespread impact on humans and natural systems. Heat
      stroke is a life-threatening condition in severe environments. The execution or
      inhibition of decision making is critical for survival in a hot environment. We
      hypothesized that, even with mild heat stress, not only executive processing, but
      also inhibitory processing may be impaired, and investigated the effectiveness of
      body cooling approaches on these processes using the Go/No-go task with
      electroencephalographic event-related potentials. Passive heat stress increased
      esophageal temperature (Tes) by 1.30 +/- 0.24  degrees C and decreased cerebral
      perfusion and thermal comfort. Mild heat stress reduced the amplitudes of the Go
      P300 component (i.e. execution) and No-go-P300 component (i.e. inhibition).
      Cerebral perfusion and thermal comfort recovered following face/head cooling,
      however, the amplitudes of the Go-P300 and No-go-P300 components remained
      reduced. During whole-body cooling, the amplitude of the Go-P300 component
      returned to the pre-heat baseline, whereas that of the No-go-P300 component
      remained reduced. These results suggest that local cooling of the face and head
      does not restore impaired cognitive processing during mild heat stress, and
      response inhibition remains impaired despite the return to normothermia.

PMID- 28497795
TI  - A simple optogenetic MAPK inhibitor design reveals resonance between
      transcription-regulating circuitry and temporally-encoded inputs.
AB  - Engineering light-sensitive protein regulators has been a tremendous
      multidisciplinary challenge. Optogenetic regulators of MAPKs, central nodes of
      cellular regulation, have not previously been described. Here we present
      OptoJNKi, a light-regulated JNK inhibitor based on the AsLOV2 light-sensor domain
      using the ubiquitous FMN chromophore. OptoJNKi gene-transfer allows optogenetic
      applications, whereas protein delivery allows optopharmacology. Development of
      OptoJNKi suggests a design principle for other optically regulated inhibitors.
      From this, we generate Optop38i, which inhibits p38MAPK in intact illuminated
      cells. Neurons are known for interpreting temporally-encoded inputs via interplay
      between ion channels, membrane potential and intracellular calcium. However, the
      consequences of temporal variation of JNK-regulating trophic inputs, potentially
      resulting from synaptic activity and reversible cellular protrusions, on
      downstream targets are unknown. Using OptoJNKi, we reveal maximal regulation of c
      Jun transactivation can occur at unexpectedly slow periodicities of inhibition
      depending on the inhibitor's subcellular location. This provides evidence for
      resonance in metazoan JNK-signalling circuits.

PMID- 28497799
TI  - Corrigendum: Oxygen impairs oligodendroglial development via oxidative stress and
      reduced expression of HIF-1alpha.

PMID- 28497798
TI  - Phosphorylation induces sequence-specific conformational switches in the RNA
      polymerase II C-terminal domain.
AB  - The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) large subunit
      cycles through phosphorylation states that correlate with progression through the
      transcription cycle and regulate nascent mRNA processing. Structural analyses of
      yeast and mammalian CTD are hampered by their repetitive sequences. Here we
      identify a region of the Drosophila melanogaster CTD that is essential for Pol II
      function in vivo and capitalize on natural sequence variations within it to
      facilitate structural analysis. Mass spectrometry and NMR spectroscopy reveal
      that hyper-Ser5 phosphorylation transforms the local structure of this region via
      proline isomerization. The sequence context of this switch tunes the activity of
      the phosphatase Ssu72, leading to the preferential de-phosphorylation of specific
      heptads. Together, context-dependent conformational switches and biased
      dephosphorylation suggest a mechanism for the selective recruitment of cis
      proline-specific regulatory factors and region-specific modulation of the CTD
      code that may augment gene regulation in developmentally complex organisms.

PMID- 28497800
TI  - Reciprocal regulation of the Il9 locus by counteracting activities of
      transcription factors IRF1 and IRF4.
AB  - The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of
      signals induced by cytokines and antigen presentation. Here we show that, within
      this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display
      opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas
      IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human
      Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4
      have opposing function on activating histone modifications, thus modulating RNA
      polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4
      abundance, suggesting an IRF1-IRF4-binding competition at the Il9 locus.
      Furthermore, IRF1 shapes Th9 cells with an interferon/Th1 gene signature.
      Consistently, IRF1 restricts the IL-9-dependent pathogenicity of Th9 cells in a
      mouse model of allergic asthma. Thus our study reveals that the molecular ratio
      between IRF4 and IRF1 balances Th9 fate, thus providing new possibilities for
      manipulation of Th9 differentiation.

PMID- 28497801
TI  - PDE4 Inhibition Restores the Balance Between Excitation and Inhibition in VTA
      Dopamine Neurons Disrupted by Repeated In Vivo Cocaine Exposure.
AB  - Phosphodiesterase type 4 (PDE4) is a family of enzymes that selectively degrade
      intracellular cAMP. PDE4 inhibitors have been shown to regulate the rewarding and
      reinforcing effects of cocaine, but the underlying mechanisms remain poorly
      understood. Here we show that pretreatments with the PDE4 inhibitor rolipram
      attenuated cocaine-induced locomotor sensitization in mice. Repeated cocaine
      exposure in vivo caused a decrease in inhibitory postsynaptic currents (IPSCs)
      and an increase in the AMPAR/NMDAR ratio in ventral tegmental area (VTA) dopamine
      neurons in midbrain slices ex vivo. Cocaine exposure disrupted the balance
      between excitation and inhibition as shown by an increase in the excitation to
      inhibition (E/I) ratio. Rolipram pretreatments in vivo prevented cocaine-induced
      reductions in GABAergic inhibition but did not further increase cocaine-induced
      potentiation of excitation, leading to the restoration of a balance between
      excitation and inhibition and normalization of the E/I ratio. In support of this
      idea, we found that repeated cocaine exposure led to an increase in the single
      unit action potential firing rate in vivo in VTA dopamine neurons, which was
      blocked by rolipram pretreatments. These results suggest that repeated cocaine
      exposure in vivo disrupts the balance between excitation and inhibition in VTA
      dopamine neurons, while PDE4 inhibition reestablishes the balance between
      excitation and inhibition through distinct mechanisms.

PMID- 28497803
TI  - Motor neuron disease: Proinflammatory monocytes might contribute to ALS
      progression.

PMID- 28497802
TI  - Data-Driven Subgroups in Depression Derived from Directed Functional Connectivity
      Paths at Rest.
AB  - Depressed patients show abnormalities in brain connectivity at rest, including
      hyperconnectivity within the default mode network (DMN). However, there is well
      known heterogeneity in the clinical presentation of depression that is overlooked
      when averaging connectivity data. We used data-driven parsing of neural
      connectivity to reveal subgroups among 80 depressed patients completing resting
      state fMRI. Directed functional connectivity paths (eg, region A influences
      region B) within a depression-relevant network were characterized using Group
      Iterative Multiple Model Estimation, a method shown to accurately recover the
      direction and presence of connectivity paths in individual participants.
      Individuals were clustered using community detection on neural connectivity
      estimates. Subgroups were compared on network features and on clinical and
      biological/demographic characteristics that influence depression prognosis. Two
      subgroups emerged. Subgroup A, containing 71% of the patients, showed a typical
      pattern of connectivity across DMN nodes, as previously reported in depressed
      patients on average. Subgroup B exhibited an atypical connectivity profile
      lacking DMN connectivity, with increased dorsal anterior cingulate-driven
      connectivity paths. Subgroup B members had an over-representation of females (87%
      of Subgroup B vs 65% of Subgroup A; chi2=3.89, p=0.049), comorbid anxiety
      diagnoses (42.9% of Subgroup B vs 17.5% of Subgroup A; chi2=5.34, p=.02), and
      highly recurrent depression (63.2% of Subgroup B vs 31.8% of Subgroup A;
      chi2=5.38, p=.02). Neural connectivity-based categorization revealed an atypical
      pattern of connectivity in a depressed patient subset that would be overlooked in
      group comparisons of depressed and healthy participants, and tracks with
      clinically relevant phenotypes including anxious depression and episodic
      recurrence. Data-driven parsing suggests heterogeneous substrates of depression;
      ideally, future work building on these findings will inform personalized
      treatment.

PMID- 28497804
TI  - Vaccine-based immunotherapeutic approaches to gliomas and beyond.
AB  - Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized
      by infiltrative growth and resistance to classic cancer therapies, which renders
      them inevitably lethal. Glioblastoma, the most common type of glioma, also
      exhibits neoangiogenesis and profound immunosuppressive properties. Accordingly,
      strategies to revert glioma-associated immunosuppression and promote tumour
      directed immune responses have been extensively explored in rodent models and in
      large clinical trials of tumour immunotherapy. This Review describes vaccination
      approaches investigated for the treatment of glioma. Several strategies have
      reached phase III clinical trials, including vaccines targeting epidermal growth
      factor receptor variant III, and the use of either immunogenic peptides or tumour
      lysates to stimulate autologous dendritic cells. Other approaches in early phases
      of clinical development employ multipeptide vaccines such as IMA-950,
      cytomegalovirus-derived peptides, or tumour-derived peptides such as heat shock
      protein-96 peptide complexes and the Arg132His mutant form of isocitrate
      dehydrogenase. However, some preclinical trial data suggest that addition of
      immunomodulatory reagents such as immune checkpoint inhibitors, transforming
      growth factor-beta inhibitors, signal transducer and activator of transcription 3
      inhibitors, or modifiers of tryptophan metabolism could augment the therapeutic
      activity of vaccination and overcome glioma-associated immunosuppression.

PMID- 28497805
TI  - The changing prevalence and incidence of dementia over time - current evidence.
AB  - Dementia is an increasing focus for policymakers, civil organizations and
      multidisciplinary researchers. The most recent descriptive epidemiological
      research into dementia is enabling investigation into how the prevalence and
      incidence are changing over time. To establish clear trends, such comparisons
      need to be founded on population-based studies that use similar diagnostic and
      research methods consistently over time. This narrative Review synthesizes the
      findings from 14 studies that investigated trends in dementia prevalence (nine
      studies) and incidence (five studies) from Sweden, Spain, the UK, the
      Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study,
      these studies indicate stable or declining prevalence and incidence of dementia,
      and some provide evidence of sex-specific changes. No single risk or protective
      factor has been identified that fully explains the observed trends, but major
      societal changes and improvements in living conditions, education and healthcare
      might have favourably influenced physical, mental and cognitive health throughout
      an individual's life course, and could be responsible for a reduced risk of
      dementia in later life. Analytical epidemiological approaches combined with
      translational neuroscientific research could provide a unique opportunity to
      explore the neuropathology that underlies changing occurrence of dementia in the
      general population.

PMID- 28497806
TI  - Management of diffuse low-grade gliomas in adults - use of molecular diagnostics.
AB  - Diffuse WHO grade II gliomas are histologically and genetically heterogeneous.
      The 2016 WHO classification redefines grade II gliomas with respect to
      morphological and molecular tumour alterations: grade II oligodendrogliomas are
      defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q,
      whereas isocitrate dehydrogenase (IDH) mutations define subclasses of
      astrocytoma. Although histological grade remains useful, the prognoses of
      patients with glioma are more tightly associated with molecular alterations than
      with grade, and chromosomal and gene array technologies are becoming increasingly
      beneficial in understanding tumour genetic heterogeneity. The indolent nature of
      the disease often creates subtle neurological symptoms that can be overlooked or
      misunderstood, resulting in delayed diagnosis. Seizures often herald the
      diagnosis, especially in patients who have IDH mutations, which are associated
      with an increased production of 2-hydroxyglutarate. Treatment paradigms have
      shifted, owing to new diagnostic criteria and new clinical trial evidence.
      Patients benefit more from chemoradiation than radiation alone, especially those
      with tumour IDH1 Arg132His mutations; gross total resection of the tumour,
      including tumours with IDH mutations, is associated with prolonged survival.
      Initial observation remains appropriate in patients whose rate of disease growth
      is not yet completely defined; such patients could include those with completely
      resected disease and those with 1p/19q codeleted tumours.

PMID- 28497807
TI  - A TRIM insertion in the promoter of Ms2 causes male sterility in wheat.
AB  - The male-sterile ms2 mutant has been known for 40 years and has become extremely
      important in the commercial production of wheat. However, the gene responsible
      for this phenotype has remained unknown. Here we report the map-based cloning of
      the Ms2 gene. The Ms2 locus is remarkable in several ways that have implications
      in basic biology. Beyond having no functional annotation, barely detectable
      transcription in fertile wild-type wheat plants, and accumulated destructive
      mutations in Ms2 orthologs, the Ms2 allele in the ms2 mutant has acquired a
      terminal-repeat retrotransposon in miniature (TRIM) element in its promoter. This
      TRIM element is responsible for the anther-specific Ms2 activation that confers
      male sterility. The identification of Ms2 not only unravels the genetic basis of
      a historically important breeding trait, but also shows an example of how a TRIM
      element insertion near a gene can contribute to genetic novelty and phenotypic
      plasticity.

PMID- 28497809
TI  - Receptor-like protein ELT1 promotes brassinosteroid signaling through interacting
      with and suppressing the endocytosis-mediated degradation of receptor BRI1.

PMID- 28497808
TI  - A unique deubiquitinase that deconjugates phosphoribosyl-linked protein
      ubiquitination.
AB  - Ubiquitination regulates many aspects of host immunity and thus is a common
      target for infectious agents. Recent studies have revealed that members of the
      SidE effector family of the bacterial pathogen Legionella pneumophila attack
      several small GTPases associated with the endoplasmic reticulum by a novel
      ubiquitination mechanism that does not require the E1 and E2 enzymes of the host
      ubiquitination machinery. In this case, ubiquitin is first activated by ADP
      ribosylation at Arg42 by a mono-ADP-ribosyltransferase activity; the intermediate
      is then cleaved by a phosphodiesterase activity also residing within SdeA,
      concomitant with the attachment of ubiquitin to serine residues of substrate
      proteins via a phosphoribosyl linker. Here we demonstrate that the effect of
      SidEs is antagonized by SidJ, an effector encoded by a gene situated in the locus
      coding for three members of the SidE family (SdeC, SdeB and SdeA). SidJ reverses
      ubiquitination of SidEs-modified substrates by cleaving the phosphodiester bond
      that links phosphoribosylated ubiquitin to protein substrates. SidJ also displays
      classical deubiquitinase activity but does not require catalytic cysteine
      residues. Further, these deubiquitinase activities of SidJ are essential for its
      role in L. pneumophila infection. Finally, the activity of SidJ is required for
      efficiently reducing the abundance of ubiquitinated Rab33b in infected cells
      within a few hours after bacterial uptake. Our results establish SidJ as a
      ubiquitin-deconjugating enzyme that functions to impose temporal regulation on
      the activity of SidE effectors. SidJ may be important in future studies of
      signaling cascades mediated by this unique ubiquitination, one that also
      potentially regulates cellular processes in eukaryotic cells.

PMID- 28497811
TI  - Polar bodies are efficient donors for reconstruction of human embryos for
      potential mitochondrial replacement therapy.

PMID- 28497810
TI  - Class I histone deacetylases are major histone decrotonylases: evidence for
      critical and broad function of histone crotonylation in transcription.
AB  - Recent studies on enzymes and reader proteins for histone crotonylation support a
      function of histone crotonylation in transcription. However, the enzyme(s)
      responsible for histone decrotonylation (HDCR) remains poorly defined. Moreover,
      it remains to be determined if histone crotonylation is physiologically
      significant and functionally distinct from or redundant to histone acetylation.
      Here we present evidence that class I histone deacetylases (HDACs) rather than
      sirtuin family deacetylases (SIRTs) are the major histone decrotonylases, and
      that histone crotonylation is as dynamic as histone acetylation in mammalian
      cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired
      HDAC but intact HDCR activity. Using these mutants we demonstrate that selective
      HDCR in mammalian cells correlates with a broad transcriptional repression and
      diminished promoter association of crotonylation but not acetylation reader
      proteins. Furthermore, we show that histone crotonylation is enriched in and
      required for self-renewal of mouse embryonic stem cells.

PMID- 28497812
TI  - Metastasis: The plastic state.

PMID- 28497814
TI  - Liver: FGF21 - the cause of having a 'sweet tooth'?

PMID- 28497813
TI  - Warming the mouse to model human diseases.
AB  - Humans prefer to live within their thermal comfort or neutral zone, which they
      create by making shelters, wearing clothing and, more recently, by regulating
      their ambient temperature. These strategies enable humans to maintain a constant
      core temperature (a trait that is conserved across all endotherms, including
      mammals and birds) with minimal energy expenditure. Although this primordial
      drive leads us to seek thermal comfort, we house our experimental animals,
      laboratory mice (Mus musculus), under conditions of thermal stress. In this
      Review, we discuss how housing mice below their thermoneutral zone limits our
      ability to model and study human diseases. Using examples from cardiovascular
      physiology, metabolic disorders, infections and tumour immunology, we show that
      certain phenotypes observed under conditions of thermal stress disappear when
      mice are housed at thermoneutrality, whereas others emerge that are more
      consistent with human biology. Thus, we propose that warming the mouse might
      enable more predictive modelling of human diseases and therapies.

PMID- 28497815
TI  - Reproductive endocrinology: Puberty timing and cancer risk.

PMID- 28497816
TI  - Corrigendum to "Eruptive inflamed seborrheic keratoses in the setting of
      endometrial adenocarcinoma" [International Journal of Women's Dermatology 1
      (2015) 155-156].
AB  - [This corrects the article DOI: 10.1016/j.ijwd.2015.07.003.].

PMID- 28497817
TI  - Rechargeable and LED-activated ZnGa2O4 : Cr3+ near-infrared persistent
      luminescence nanoprobes for background-free biodetection.
AB  - Persistent luminescence nanoparticles (PLNPs) have shown great promise in the
      field of biomedicine, but are currently limited by the challenge in the synthesis
      of high-quality PLNPs with bright persistent luminescence and a long afterglow
      time. Herein, we report a facile strategy for the synthesis of monodisperse,
      rechargeable and LED-activated ZnGa2O4 : Cr3+ near-infrared (NIR) PLNPs based on
      a modified solvothermal liquid-solid-solution method. The as-synthesized PLNPs
      are not only flexible for bioconjugation, but could also circumvent the
      limitation of the weak persistent luminescence and short afterglow time that most
      PLNPs confronted owing to their rechargeable capability. It was unraveled that
      both thermal activation and quantum tunneling mechanisms contributed to the
      afterglow decay of the PLNPs, and the quantum tunneling was found to dictate the
      LED-activated afterglow intensity and lasting time. Furthermore, by utilizing the
      superior excitation-free persistent luminescence, we demonstrated for the first
      time the application of biotinylated ZnGa2O4 : Cr3+ PLNPs as background-free
      luminescent nano-bioprobes for sensitive and specific detection of avidin in a
      heterogeneous assay with a limit of detection down to ~150 pM, thus revealing the
      great potential of these NIR PLNPs in ultrasensitive biodetection and bioimaging.

PMID- 28497818
TI  - New D-D-pi-A triphenylamine-coumarin sensitizers for dye-sensitized solar cells.
AB  - Three D-D-pi-A triphenylamine-coumarin sensitizers were designed and synthesized
      with a triphenylamine and coumarin double donor and a cyanoacrylic acid acceptor.
      Thiophene, bithiophene and phenylthiophene were used as pi-bridges, respectively,
      and the effects of different pi-bridges on the photophysical properties and
      photovoltaic performance were investigated. With the incorporation of an
      additional thiophene unit, the bithiophene pi-bridge contributes to better light
      absorption and hence superior JSC compared with the thiophene pi-bridge. Although
      the dye with phenylthiophene pi-bridge exhibits an inferior absorption spectrum
      to that with the thiophene pi-bridge, it gives a photoelectrical conversion
      efficiency of 4.99% and exhibits the best photovoltaic performance of the three
      sensitizers, ascribed to its efficient photon-to-current conversion efficiency,
      slow charge recombination rate and good electron injection efficiency.

PMID- 28497819
TI  - Disorder-induced transition from grain boundary to bulk dominated ionic diffusion
      in pyrochlores.
AB  - We use molecular dynamics simulations to investigate the role of grain boundaries
      (GBs) on ionic diffusion in pyrochlores, as a function of the GB type, chemistry
      of the compound, and level of cation disorder. We observe that the presence of
      GBs promotes oxygen transport in ordered and low-disordered systems, as the GBs
      are found to have a higher concentration of mobile carriers with higher
      mobilities than in the bulk. Thus, in ordered samples, the ionic diffusion is 2D,
      localized along the grain boundary. When cation disorder is introduced, bulk
      carriers begin to contribute to the overall diffusion, while the GB contribution
      is only slightly enhanced. In highly disordered samples, the diffusive behavior
      at the GBs is bulk-like, and the two contributions (bulk vs. GB) can no longer be
      distinguished. There is thus a transition from 2D/GB dominated oxygen diffusivity
      to 3D/bulk dominated diffusivity versus disorder in pyrochlores. These results
      provide new insights into the possibility of using internal interfaces to enhance
      ionic conductivity in nanostructured complex oxides.

PMID- 28497820
TI  - Reducibility of ZrO2/Pt3Zr and ZrO2/Pt 2D films compared to bulk zirconia: a
      DFT+U study of oxygen removal and H2 adsorption.
AB  - Oxide reducibility is an important property that determines the chemical and
      physical behavior of the materials under working conditions. Zirconia is a non
      reducible oxide that exhibits high resistance to the loss of oxygen and low
      reactivity towards hydrogen, two typical processes involved in oxide reduction.
      Oxide reducibility can change substantially by nanostructuring (e.g. formation of
      nanoparticles). In this study, we investigate theoretically by means of DFT+U
      calculations including dispersion interactions the properties of 2D zirconia
      films supported on a Pt3Zr alloy and Pt metal surfaces, two systems recently
      prepared experimentally. The results show that the supported ZrO2 ultrathin films
      behave very differently from the corresponding bulk oxide, with a low formation
      energy of oxygen vacancies, and a clear tendency to split the H2 molecule
      homolytically with direct reduction of the oxide. The comparison of free-standing
      and supported ZrO2 films shows that these peculiar properties are not due to the
      formation of a 2D nanostructure, but rather to the presence of the metal support
      and of a metal/oxide interface. The results provide evidence for the uncommon
      properties of supported 2D oxides.

PMID- 28497821
TI  - A cleft type receptor which combines an oxyanion hole with electrostatic
      interactions.
AB  - A receptor for carboxylic acids which combines an oxyanion-hole structure with
      electrostatic forces has been prepared. X-ray diffraction studies have been
      carried out to evaluate the geometry of both the free receptor and its associated
      species with several carboxylic acids and many different arrangements have been
      discovered for the H-bond pattern in the associated species.

PMID- 28497822
TI  - B-DNA model systems in non-terran bio-solvents: implications for structure,
      stability and replication.
AB  - We have computationally analyzed a comprehensive series of Watson-Crick and
      mismatched B-DNA base pairs, in the gas phase and in several solvents, including
      toluene, chloroform, ammonia, methanol and water, using dispersion-corrected
      density functional theory and implicit solvation. Our analyses shed light on how
      the molecular-recognition machinery behind life's genetic code depends on the
      medium, in order to contribute to our understanding of the possibility or
      impossibility for life to exist on exoplanetary bodies. Calculations show how a
      common non-terran environment like ammonia, less polar than water, exhibits
      stronger hydrogen-bonding affinities, although showing reduced selectivities
      towards the correct incorporation of Watson-Crick base pairs into the backbone.
      Thus, we prove the viability of DNA replication in a non-terran environment.

PMID- 28497824
TI  - Photochemical synthesis of CdS-MIL-125(Ti) with enhanced visible light
      photocatalytic performance for the selective oxidation of benzyl alcohol to
      benzaldehyde.
AB  - In this study, we decorated CdS on the surface of MIL-125(Ti) using a
      photochemical method to prepare the CdS-MIL-125(Ti) nanocomposites. The obtained
      samples were characterized by a series of techniques such as X-ray diffraction
      (XRD), scanning electron microscopy (SEM), photoluminescence (PL) spectra,
      electrochemical measurements and UV-Vis diffuse reflectance spectra (DRS). The
      results show that the CdS nanoparticles were highly dispersed on surface of MIL
      125(Ti). The combination will promote the separation of electron-hole pairs and
      increase the dispersity of CdS. The nanocomposites were subsequently used as
      photocatalysts in the selective oxidation of benzyl alcohol to benzaldehyde using
      the molecular oxygen as the oxidant. The nanocomposites show excellent
      performance in the photocatalytic reaction under visible light irradiation. The
      conversion of benzyl alcohol to benzaldehyde was about 20.1% with no by-products
      observed.

PMID- 28497825
TI  - Enhanced photocatalytic hydrogen evolution from in situ formation of few-layered
      MoS2/CdS nanosheet-based van der Waals heterostructures.
AB  - Here we report for the first time that the H2 bubbles generated by photocatalytic
      water splitting are effective in the layer-by-layer exfoliation of MoS2
      nanocrystals (NCs) into few layers. The as-obtained few layers can be in situ
      assembled with CdS nanosheets (NSs) into van der Waals heterostructures (vdWHs)
      of few-layered MoS2/CdS NSs which, in turn, are effective in charge separation
      and transfer, leading to enhanced photocatalytic H2 production activity. The few
      layered MoS2/CdS vdWHs exhibited a H2 evolution rate of 140 mmol g(CdS)-1 h-1 and
      achieved an apparent quantum yield of 66% at 420 nm.

PMID- 28497826
TI  - Twisting with a twist: supramolecular helix fluctuations in chiral nematics.
AB  - Most theoretical descriptions of lyotropic cholesteric liquid crystals to date
      focus on homogeneous systems in which the rod concentration, as opposed to the
      rod orientation, is uniform. In this work, we build upon the Onsager-Straley
      theory for twisted nematics and study the effect of weak concentration gradients,
      generated by some external potential, on the cholesteric twist. We apply our
      theory to chiral nematics of nanohelices in which the supramolecular helix sense
      is known to spontaneously change sign upon variation of particle concentration,
      passing through a so-called compensation point at which the mesoscopic twist
      vanishes. We show that the imposed field offers exquisite control of the
      handedness and magnitude of the helicoidal director field, even at weak field
      strengths. Within the same framework we also quantify the director fluctuation
      spectrum and find evidence for a correlation length diverging at the compensation
      point.

PMID- 28497823
TI  - Natural products modulating the hERG channel: heartaches and hope.
AB  - Covering: 1996-December 2016The human Ether-a-go-go Related Gene (hERG) channel
      is a voltage-gated potassium channel playing an essential role in the normal
      electrical activity in the heart. It is involved in the repolarization and
      termination of action potentials in excitable cardiac cells. Mutations in the
      hERG gene and hERG channel blockage by small molecules are associated with
      increased risk of fatal arrhythmias. Several drugs have been withdrawn from the
      market due to hERG channel-related cardiotoxicity. Moreover, as a result of its
      notorious ligand promiscuity, this ion channel has emerged as an important
      antitarget in early drug discovery and development. Surprisingly, the hERG
      channel blocking profile of natural compounds present in frequently consumed
      botanicals (i.e. dietary supplements, spices, and herbal medicinal products) is
      not routinely assessed. This comprehensive review will address these issues and
      provide a critical compilation of hERG channel data for isolated natural products
      and extracts over the past two decades (1996-2016). In addition, the review will
      provide (i) a solid basis for the molecular understanding of the physiological
      functions of the hERG channel, (ii) the translational potential of in vitro/in
      vivo results to cardiotoxicity in humans, (iii) approaches for the identification
      of hERG channel blockers from natural sources, (iv) future perspectives for
      cardiac safety guidelines and their applications within phytopharmaceuticals and
      dietary supplements, and (v) novel applications of hERG channel modulation (e.g.
      as a drug target).

PMID- 28497827
TI  - A dsDNA model optimized for electrokinetic applications.
AB  - We present a coarse-grained (CG) model of a charged double-stranded DNA immersed
      in an electrolyte solution that can be used for a variety of electrokinetic
      applications. The model is based on an earlier rigid and immobile model of Weik
      et al. and includes now semi-flexibility and mobility, so that DNA dynamics can
      be sufficiently captured to simulate a full nanopore translocation process. To
      this end we couple the DNA hydrodynamically via a raspberry approach to a lattice
      Boltzmann fluid and parametrize the counterions with a distant dependent
      friction. The electrokinetic properties of the CG DNA model inside an infinite
      cylinder is fitted against experimental data from Smeets et al. and all-atom
      simulation data from Kesselheim et al. The stiffness of our CG DNA is modeled via
      a harmonic angle potential fitted against experimental data of Brunet et al.
      Finally, the quality of our tuned parameters is tested by measuring the
      electrophoretic mobility of our DNA model for various numbers of base pairs and
      salt concentrations. Our results compare excellently with the experimental data
      sets of Stellwagen et al. and Hoagland et al.

PMID- 28497828
TI  - Structural analysis of micrometer-long gold nanowires using a wormlike chain
      model and their rheological properties.
AB  - The recent growing interest in the applications of gold nanowires (AuNWs) as
      flexible materials has raised the fundamental issue of how their mechanical
      properties are related to their morphology. In this work, to address this issue,
      the systematic synthesis of AuNWs, their structural analysis, and their
      rheological investigation were demonstrated. The structural analysis of AuNWs was
      performed based on TEM observations and light-scattering experiments. From these
      observations, it was found that the length of AuNWs varies from nanometer to
      micrometer depending on the reaction time while a constant width of 1.6 nm is
      maintained. On the basis of static light-scattering experiments and a wormlike
      chain model, the structural parameters of AuNWs during their growth were
      successfully obtained. When the contour length of AuNWs reached around 5 MUm, the
      AuNW solution showed non-Newtonian behavior and appeared to behave as a gel.
      Dynamic viscoelasticity measurements indicated that such viscous behavior is
      responsible for entanglement between AuNWs. It is concluded that AuNWs are
      analogous with conventional polymers in terms of both their structure and their
      rheological behavior.

PMID- 28497829
TI  - Organocatalytic synthesis of axially chiral atropisomers.
AB  - This Review summarises the recent progress made in the organocatalytic synthesis
      of atropisomeric compounds. Methodologies based on dynamic kinetic resolution and
      direct access to BINOL-like biaryls are described. A particular emphasis is given
      to reaction mechanisms and to the development of strategies to obtain stable
      products by increasing the barrier to atropisomer interconversion during the
      reaction.

PMID- 28497830
TI  - FeCl3 catalysed 7-membered ring formation in a single pot: a new route to indole
      fused oxepines/azepines and their cytotoxic activity.
AB  - Various oxepine and azepine fused N-heterocyclic derivatives were synthesized
      using a new and one-pot reaction of 2,3-dichloro quinoxaline/pyrazine with 2-(1H
      indol-2-yl)phenol/aniline in the presence of 25 mol% FeCl3. The reaction
      proceeded via C-C bond followed by C-X (X = O or N) bond formation to construct
      the central 7-membered ring, affording the desired products in good yields. The
      structure assignment was confirmed by the single crystal X-ray analysis of a
      synthesized oxepine fused N-heterocycle derivative. Most of the synthesized
      compounds were found to be promising when tested for their anti-proliferative
      properties against cervical and breast cancer cell lines.

PMID- 28497831
TI  - Tuning electric field aligned CNT architectures via chemistry, morphology, and
      sonication from micro to macroscopic scale.
AB  - Electric-field alignment of carbon nanotubes (CNT) is widely used to produce
      composite materials with anisotropic mechanical, electrical, and optical
      properties. Nevertheless, consistent results are difficult to achieve, and even
      under identical electric field conditions the resulting aligned morphologies can
      vary over MUm to cm length scales. In order to improve reproducibility, this
      study addresses (1) how solution processing steps (oxidation, sonication) affect
      CNT properties, and (2) how CNT chemistry, morphology, and dispersion influence
      alignment. Aligned CNT were deposited onto PVDF membranes using a combination of
      electric-field alignment and vacuum-filtration. At each step in solution
      processing, the CNT chemistry (oxygen content) and morphology (length/diameter)
      were characterized and compared to the final aligned morphology. Well-dispersed
      CNT with high oxygen content (>8.5%O) yielded uniform membrane coatings and
      microscopically aligned CNT, whereas CNT with low oxygen CNT (<2.2%O) produced
      aligned bundles visible at a macroscopic level, but microscopically the
      individual CNT remained disordered. Based on regression analysis, CNT with larger
      mean length and diameter, smaller length and diameter variation, and higher
      oxygen content yielded increased electrical anisotropy, and bath sonication was
      slightly preferable to probe sonication for initial dispersion.

PMID- 28497832
TI  - A unique semiconductor-carbon-metal hybrid structure design as a counter
      electrode in dye-sensitized solar cells.
AB  - The catalytic activity of counter electrodes (CEs) severely restricts the
      photovoltaic conversion efficiency of dye-sensitized solar cells. However,
      electrons trapped by bulk defects greatly reduce the catalytic activity of the
      CE. In this study, we report a novel In2S3-C-Au hybrid structure designed by
      simply decorating Au particles on the surface of carbon-coated hierarchical In2S3
      flower-like architectures, which could avoid the abovementioned problems. This
      effect can be attributed to the unique contribution of indium sulfide, carbon,
      and Au from the hybrid structure, as well as to their synergy. Electrochemical
      measurements revealed that the hybrid structure possessed high catalytic activity
      and electrochemical stability for the interconversion of the redox couple I3-/I-.
      Moreover, this superior performance can be incorporated into the dye-sensitized
      solar cells system. We used this hybrid structure as a counter electrode by
      casting it on an FTO substrate to form a film, which displayed better
      photovoltaic conversion efficiency (8.91%) than the commercial Pt counterpart
      (7.67%).

PMID- 28497833
TI  - Formic acid catalyzed isomerization of protonated cytosine: a lower barrier
      reaction for tautomer production of potential biological importance.
AB  - Tautomerism in nucleotide bases is one of the possible mechanisms of DNA
      mutation. In spite of numerous studies on the structure and energy of protonated
      cytosine tautomers, little information is available on the process of their intra
      and intermolecular tautomerizations. The catalytic ability of H2O, HCOOH, and
      the HCOOHH2O group to facilitate the tautomerism of the Cyt2t+ to CytN3+ isomer
      has been studied. It is shown that the activation free energies of tautomerism in
      the gas phase are 161.17, 58.96, 26.06, and 15.69 kJ mol-1, respectively, when
      the reaction is carried out in the absence and presence of H2O, HCOOH, or the
      HCOOHH2O group. The formation of a doubly hydrogen bonded transition state is
      central to lowering the activation free energy and facilitating the
      intramolecular hydrogen atom transfer that is required for isomerization. In the
      aqueous phase, although the solvent effects of water significantly decrease the
      activation free energy of intramolecular tautomerization, the isomerization of
      the Cyt2t+ to CytN3+ isomer remains unfavorable, and the HCOOH and HCOOHH2O group
      mediated mechanisms are still more favorable. Meanwhile, conventional transition
      state theory (CTST) followed by Wigner tunneling correction is then applied to
      estimate the rate constants. The rate constant with Wigner tunneling correction
      for direct tautomerization is obviously smaller than that of HCOOH-mediated
      tautomerization, which is the most plausible mechanism. Finally, another
      important finding is that the product complex (CytN3+HCOOH) is in the rapid
      tautomeric equilibrium with the reaction complex (Cyt2t+HCOOH) (tau99.9% = 3.84 *
      10-12 s), which is implemented by the mechanism of the concerted synchronous
      double proton transfer. Its lifetime of the formed CytN3+HCOOH complex (tau =
      8.33 * 10-9 s) is almost one order of magnitude larger than the time required for
      the replication machinery to forcibly dissociate a base pair into the monomers
      during DNA replication (several ns), which is further dissociated into the CytN3+
      and HCOOH monomers. The results of the present study demonstrate the feasibility
      of acid catalysis for DNA base isomerization reactions that would otherwise be
      forbidden.

PMID- 28497834
TI  - The effect of carbohydrate structures on the hydrogelation ability and morphology
      of self-assembled structures of peptide-carbohydrate conjugates in water.
AB  - We describe the construction of peptide-carbohydrate conjugates, namely
      glycopeptides, capable of self-assembling in water. We found that disaccharide
      structures (epimer or glycosidic-bond geometry) appended to the glycopeptides
      have a noticeable effect on the hydrogel formation ability as well as the
      morphology of the self-assembled structures. The soft materials consisting of
      self-assembled structures with carbohydrates on their surface and various types
      of morphologies might be useful as matrices to investigate the function of
      carbohydrates in biological events.

PMID- 28497835
TI  - Revealing the electrophilicity of N-Ac indoles with FeCl3: a mechanistic study.
AB  - Herein, we report a mechanistic exploration of the unusual FeCl3-mediated
      hydroarylation of N-Ac indoles. Electron density topology analysis of a crystal,
      in situ IR monitoring, Hammett and Taft studies as well as DFT computations
      allowed us to determine that activation of acetyl with FeCl3 and of the C2[double
      bond, length as m-dash]C3 bond with a proton is involved.

PMID- 28497836
TI  - Visible light initiated release of calcium ions through photochemical electron
      transfer reactions.
AB  - Photolysis of anthraquinone or flavin photosensitizers in the presence of calcium
      EDTA complexes results in decomposition of the EDTA complex, releasing free Ca2+.
      In the case of the flavin sensitizers, it is shown that millimolar concentrations
      of Ca2+ can be released using visible light (>440 nm) and with quantum yields as
      high as 0.31. The utility of this system is further demonstrated by in situ
      photogelation of an alginate solution.

PMID- 28497837
TI  - Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in
      the Czech/Slav and Czech Roma/Gypsy populations.
AB  - Lactase non-persistence (leading to primary lactose intolerance) is a genetically
      dependent inability to digest lactose in adulthood. As part of the human
      adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates
      adult expression of lactase) developed, spread and participated in the adaptation
      to dairying. This variant is associated with lactase activity persistence, and
      its carriers are able to digest lactose. We compared the frequencies of lactase
      13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma
      (N = 300), two ethnically different groups where this polymorphism has not yet
      been analysed. Allelic frequencies significantly differed between the populations
      (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in
      76% of the individuals, which is in agreement with frequencies among
      geographically neighbouring populations. In the Czech Gypsy/Roma population, only
      27% of the adults were carriers of at least one lactase persistence allele,
      similar to the Indian population. In agreement with this result, dairy product
      consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech
      Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs
      populations, the presence of carriers of the lactase persistence allele was
      similar in subjects self-reporting the consumption of unfermented/fresh milk, in
      comparison to the others.

PMID- 28497838
TI  - Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in
      women.
AB  - Butyrylcholinesterase (BChE) activity and polymorphisms in its encoding gene had
      previously been associated with metabolic traits of obesity. This study
      investigated the association of three single nucleotide polymorphisms (SNPs) in
      the BCHE gene: -116G > A (rs1126680), 1615GA (rs1803274), 1914A < G (rs3495),
      with obesity and lipid metabolism markers, body mass index (BMI), total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, and BChE enzymatic
      activity in obese (BMI>=30/n = 226) and non-obese women (BMI < 25/n = 81). BCHE
      SNPs genotyping was obtained by TaqMan allelic discrimination assay and by RFLP
      PCR. Plasmatic BChE activity was measured using propionylthiocholine as
      substrate. Similar allele frequencies were found in obese and non-obese women for
      the three studied SNPs (p > 0.05). The dominant and recessive models were tested,
      and different effects were found. The -116A allele showed a dominant effect in
      BChE activity reduction in both non-obese and obese women (p = 0.045 and p <
      0.001, respectively). The 1914A > G and 1615GA SNPs influenced the TG levels only
      in obese women. The 1914G and the 1615A alleles were associated with decreased
      plasma levels of TG. Thus, our results suggest that the obesity condition,
      characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.

PMID- 28497839
TI  - Evaluation of the association between the TAS1R2 and TAS1R3 variants and food
      intake and nutritional status in children.
AB  - Taste perception plays a key role in determining individual food preferences and
      dietary habits and may influence nutritional status. This study aimed to
      investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266
      C/T - rs35744813) variants with food intake and nutritional status in children
      followed from birth until 7.7 years old. The nutritional status and food intake
      data of 312 children were collected at three developmental stages (1, 3.9 and 7.7
      years old). DNA was extracted from blood samples and the polymorphisms were
      analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes
      as the detection method. Food intake and nutritional status were compared among
      individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9
      years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism
      ingested less sugar and sugar-dense foods than children who were *Ile carriers.
      This finding demonstrated that a genetic variant of the T1R2 taste receptor is
      associated with the intake of different amounts of high sugar-content foods in
      childhood. This association may provide new perspectives for studying dietary
      patterns and nutritional status in childhood.

PMID- 28497840
TI  - Risk factors of atrial fibrillation recurrence despite successful radiofrequency
      ablation of accessory pathway: At 11 years of follow-up.
AB  - BACKGROUND: Previous reports on patients with radiofrequency catheter ablation
      (RFCA) of accessory pathway (AP) and atrial fibrillation (AF) include only short
      follow-up periods. The aim of this study was to analyze predictors of recurrence
      of AF in patients after successful RFCA of APs over long term follow-up periods.
      METHODS: Of the 1,007 patients who underwent non-pharmacological treatment of APs
      (between the years 1993-2008), data of 100 consecutive patients were
      retrospectively analyzed (75 men, mean age 43.6 +/- 14.7), with the longest
      period of follow-up (mean 11.3 +/- 3.5 years) after successful RFCA of AP. In
      Group 1, there were 72 patients (54 men, mean age 40.66 +/- 13.85 years) without
      documented episodes of AF after RFCA of AP. Group 2 consisted of 28 patients (21
      men, mean age 50.79 +/- 14.49 years) with AF episodes despite successful
      elimination of AP. RESULTS: In univariate analysis, patients from Group 1 were
      significantly younger at the time of abla-tion than patients from Group 2 (40.66
      +/- 13.85 vs. 50.79 +/- 14.49 years; p = 0.002), had shorter his!tory of AF
      episodes (4.11 +/- 4.07 vs. 8.25 +/- 7.50 years; p = 0.024) and had less
      frequently documented atrial tachycardia (AT) prior to ablation (3.39 vs. 20.00%
      years; p = 0.022). In multivariate analysis, the history of AF in years (p =
      0.043), was an independent risk factor for AF recurrences. CONCLUSIONS: Older
      patient age, longer history of AF and AT prior to RFCA of APs identified a sub
      group of patients who required additional treatment. In the multivariate
      analysis, the history of AF in years (p = 0.043) was a risk factor for AF
      recurrence.

PMID- 28497841
TI  - Effect of fluid resuscitation with balanced solutions on platelets: In vitro
      simulation of 20% volume substitution.
AB  - BACKGROUND: Fluid resuscitation in massive bleeding may cause coagulation
      disorders by dilution of platelets and clotting factors or by the impact on their
      function. The aim of this study was to investigate the effects of balanced
      crystalloid and colloid solutions on platelets in vitro using complex assessment
      of coagulation. METHODS: The study group was comprised of 32 American Society of
      Anesthesiologists physical status class I male volunteers, aged 21-35 (29 +/- 4)
      years, weighting 59-103 (81.2 +/- 9.8) kg. Whole blood samples were diluted at a
      4:1 ratio with the following fluids: balanced crystalloid (Plasmalyte(r)), 6%
      hydroxyethyl starch 130/0.4 (Volulyte(r)) and succinylated gelatin
      (Geloplasma(r)). Coagulation was as-sessed using standard morphology, rotational
      thromboelastometry and aggregometry. RESULTS: Dilution with all fluids caused
      statistically significant drop in the number of platelets (p < 0.01) but the
      effect did not differ between solutions (p > 0.05 for all). Other platelet
      parameters, such as platelet distribution width, mean platelet volume and
      platelet-large cell ratio were not affected by the solutions. Hemodilution had no
      effect on platelet function (p = 0.1). Decreased platelet component of clot
      strength was found for all three fluids (p < 0.05), although the effect for
      colloids was more pronounced. CONCLUSIONS: The effect of balanced crystalloids
      and colloids on platelet aggregation was insignificant, even after 20% volume
      substitution with the resuscitation fluids. (.

PMID- 28497842
TI  - Macrophagic enhancement in optical coherence tomography imaging by means of
      superparamagnetic iron oxide nanoparticles.
AB  - BACKGROUND: The ability of optical coherence tomography (OCT) to visualise
      macrophages in vivo in coronary arteries is still controversial. We hypothesise
      that imaging of macrophages in OCT could be enhanced by means of
      superparamagnetic nanoparticles. METHODS: We compared the optical backscattering
      and attenuation of cell pellets containing RAW 264.7 macrophages with those of
      macrophagic cell pellets labelled with very small superparamagnetic oxydised
      nanoparticles (VSOP) by means of light intensity analysis in OCT. The labelled
      macrophages were incubated with VSOP at a concentration of 1 mM Fe, corresponding
      to intracellular iron concentrations of 8.8 pg/cell. To study the effect of
      intracellular accumulation on the backscattering, VSOP dilutions without cells
      were also compared. OCT pullbacks of the PCR tubes containing the cell pellets
      were obtained and light intensity analysis was performed on raw OCT images in
      polar view, after normalisation by the backscattering of the PCR tube. The
      backscattering was estimated by the peak normalised intensity, whilst the
      attenuation was estimated by the number of pixels between the peak and the
      normalised intensity 1 (peak-to-one). RESULTS: VSOP-loaded macrophages have
      higher backscattering than the corresponding unlabelled macrophages (peak
      normalised intensity 6.30 vs. 3.15) with also slightly higher attenuation (peak
      toone 61 vs. 66 pixels). The backscattering of the nanoparticles in suspension
      was negligible in the light intensity analysis. CONCLUSIONS: VSOP increase
      significantly the optical backscattering of macrophages in the nearinfrared
      region, with minimal increase in signal attenuation. This finding enables the
      enhancement of macrophages in conventional OCT imaging with an easily
      implementable methodology.

PMID- 28497843
TI  - Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing.
AB  - BACKGROUND: Despite left ventricular (LV) dysfunction contributing to mortality
      in chronic heart failure (HF), the molecular mechanisms of LV failure continues
      to remain poorly understood and myocardial biomarkers have yet to be identified.
      The aim of this pilot study was to investigate specific transcriptome changes
      occurring in cardiac tissues of patients with HF compared to healthy condition
      patients to improve diagnosis and possible treatment of affected subjects.
      METHODS: Unlike other studies, only dilated cardiomyopathy (DCM) (n = 2) and
      restrictive cardiomyopathy (RCM) (n = 2) patients who did not report family
      history of the disease were selected with the aim of obtaining a homogeneous
      population for the study. The transcriptome of all patients were studied by RNA
      sequencing (RNA-Seq) and the read counts were adequately filtered and normalized
      using a recently developed user-friendly tool for RNA-Seq data analysis, based on
      a new graphical user interface (RNA-SeqGUI). RESULTS: By using this approach in a
      pairwise comparison with healthy donors, we were able to identify DCM- and RCM
      specific expression signatures for protein-coding genes as well as for long
      noncoding RNAs (lncRNAs). Differential expression of 5 genes encoding different
      members of the mediator complex was disclosed in this analysis. Interestingly, a
      significant alteration was found for genes which had never been associated with
      HF until now, and 27 lncRNA/mRNA pairs that were significantly altered in HF
      patients. CONCLUSIONS: The present findings revealed specific expression pattern
      of both protein-coding and lncRNAs in HF patients, confirming that new LV
      myocardial biomarkers could be reliably identified using Next-Generation
      Sequencing-based approaches.

PMID- 28497844
TI  - Echocardiographic evaluation of right ventricular systolic function: The
      traditional and innovative approach.
AB  - Estimation of right ventricular (RV) performance still remains technically
      challenging due to its anatomical and functional distinctiveness. The current
      guidelines for the echocardiographic quantification of RV function recommend
      using multiple indices to describe the RV in a thorough and comprehensive manner,
      such as RV index of myocardial performance, tricuspid annular plane systolic
      excursion, fractional area change, Doppler tissue imaging-derived tricuspid
      lateral annular systolic velocity (S'-wave), three-dimensional RV ejection
      fraction (3D RVEF), RV longitudinal strain (RVLS)/strain rate by speckle-
      tracking echocardiography (STE). Among these, the last one mentioned here is an
      innovative and a particularly promising tool that yields more precise information
      about complex regional and global RV mechanics. STE was initially designed to
      evaluate left ventricular function, but recently it has been introduced to assess
      RV performance, which is difficult due to its unique structure and physiology.
      Many studies have shown that both free wall and 6-segment RVLS present a stronger
      correlation with the RVEF assessed by cardiac magnetic resonance than
      conventional parameters and seem to be more sensitive in detecting myocardial
      dysfunction at an earlier, subclinical stage.

PMID- 28497845
TI  - Comparison of dual antiplatelet therapy versus oral anticoagulation following
      transcatheter aortic valve replacement: A retrospective single-center registry
      analysis.
AB  - BACKGROUND: The choice of optimal antithrombotic regimen after transcatheter
      aortic valve replace-ment (TAVR) remains a matter of debate. The objective of
      this study was to compare both efficacy and safety outcomes based on the type of
      antithrombotic therapy prescribed after TAVR Methods: This is a retrospective
      analysis of 514 consecutive patients treated with either dual antiplate!let
      therapy (DAPT) (n = 315; 61.3%) or oral anticoagulation (OAC) plus clopidogrel (n
      = 199; 38.7%) for a minimum of 3 months after TAVR followed by antiplatelet
      monotherapy or OAC only, respectively. Patients had pre-defined clinical and
      echocardiographic follow-ups at 30 days, 6 and 12 months. The key efficacy
      endpoint was a composite of all-cause death, myocardial infarction, stroke and
      valve throm!bosis at 1 year. The key safety endpoint was the occurrence of life
      threatening/major bleeding at 1 year. RESULTS: Baseline characteristics did not
      differ between both groups, except for a higher incidence of atrial fibrillation
      in the OAC group. No significant differences in both efficacy and safety
      endpoints were observed at 30 days and 6 months. At 1 year, the key efficacy
      endpoint occurred in 21.5% of the DAPT group compared to 19.7% of the OAC group
      (p = 0.61). The key safety endpoint occurred in 25.1% and 27.8%, respectively (p
      = 0.53). However, after 1 year valve thrombosis was reported in 8 (2.5%) patients
      in the DAPT group but not in the OAC group (p = 0.02). CONCLUSIONS: OAC after
      TAVR seems to reduce the risk of clinical valve thrombosis without a statisti
      cally significant increase in bleeding complications.

PMID- 28497846
TI  - Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective
      Multicenter Analysis.
AB  - Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete
      surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients
      with OS have local or systemic recurrence. Some patients survive multiple
      recurrences, but overall survival after OS recurrence is poor. This analysis aims
      to describe and identify factors influencing post-relapse survival (PRS) after a
      second OS relapse. Methods This is a retrospective analysis of 60 patients with a
      second relapse of OS of the extremities in 2 Italian centers between 2003 and
      2013. Results Treatment for first and subsequent relapses was planned according
      to institutional guidelines. After complete surgical remission (CSR) following
      the first recurrence, patients experienced a second OS relapse with a median
      disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients
      (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5
      years. Lung disease only correlated with better survival at 5 years (33.6%)
      compared with other sites of recurrence (5%; p = 0.008). Patients with a single
      pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who
      achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001)
      benefited patients without a third CSR. Conclusions This analysis confirms the
      importance of an aggressive, repeated surgical approach. Lung metastases only,
      the number of lesions, DFI and CSR influenced survival. It also confirms the
      importance of chemotherapy in patients in whom surgical treatment is not
      feasible.

PMID- 28497847
TI  - Pathogenesis, clinical manifestations and management of immune checkpoint
      inhibitors toxicity.
AB  - Immune checkpoint inhibitors have emerged as an effective treatment for several
      tumor types and their use in clinical practice is expected to further increase in
      the immediate future. Although these agents are well tolerated, they are
      associated with a peculiar spectrum of toxicity, which is immune mediated and may
      potentially affect every organ. However, immune-related adverse events are mostly
      reversible if promptly diagnosed and adequately treated. Therefore, it is crucial
      that medical oncologists know how to diagnose and treat immune-related adverse
      events. This review focuses on the pathogenesis, clinical manifestations and
      management of immune-related toxicity of anti-CTLA-4 and anti-PD-1 antibodies.

PMID- 28497848
TI  - Isolation of subtelomeric sequences of porcine chromosomes for translocation
      screening reveals errors in the pig genome assembly.
AB  - Balanced chromosomal aberrations have been shown to affect fertility in most
      species studied, often leading to hypoprolificacy (reduced litter size) in
      domestic animals such as pigs. With an increasing emphasis in modern food
      production on the use of a small population of high quality males for artificial
      insemination, the potential economic and environmental costs of hypoprolific
      boars, bulls, rams etc. are considerable. There is therefore a need for novel
      tools to facilitate rapid, cost-effective chromosome translocation screening.
      This has previously been achieved by standard karyotype analysis; however, this
      approach relies on a significant level of expertise and is limited in its ability
      to identify subtle, cryptic translocations. To address this problem, we developed
      a novel device and protocol for translocation screening using subtelomeric probes
      and fluorescence in situ hybridisation. Probes were designed using BACs
      (bacterial artificial chromosomes) from the subtelomeric region of the short (p
      arm) and long (q-arm) of each porcine chromosome. They were directly labelled
      with FITC or Texas Red (p-arm and q-arm respectively) prior to application of a
      'Multiprobe' device, thereby enabling simultaneous detection of each individual
      porcine chromosome on a single slide. Initial experiments designed to isolate
      BACs in subtelomeric regions led to the discovery of a series of incorrectly
      mapped regions in the porcine genome assembly (from a total of 82 BACs, only 45
      BACs mapped correctly). Our work therefore highlights the importance of accurate
      physical mapping of newly sequenced genomes. The system herein described allows
      for robust and comprehensive analysis of the porcine karyotype, an adjunct to
      classical cytogenetics that provides a valuable tool to expedite efficient, cost
      effective food production.

PMID- 28497849
TI  - Differential investment in body girths by sex: Evidence from 3D photonic scanning
      in a Thai cohort.
AB  - OBJECTIVES: Life history trade-offs may manifest between competing organs and
      tissues in the body. Sexual dimorphism in tissue investment is well-established
      in humans, with sex-associated body shape differences linked to natural and
      sexual selection. This study uses three-dimensional (3D) photonic scanning to
      test whether males and females differentially invest energy in various body
      regions in relation to two independent proxies of growth. MATERIALS AND METHODS:
      Body shape data (multiple girths) came from a Thai cohort (n = 11,610; 53%
      female; age range 21-88 years). Weight was considered a proxy for recent energy
      acquisition. Stature represented completed growth, a proxy for energy acquisition
      earlier in life. The data were analyzed using growth-proxy by sex interaction log
      log regression models adjusting for age, salary and number of children. RESULTS:
      For a given percentage increase in weight, females showed greater percentage
      increases than males in girths of the arm, chest, hip, thigh, knee and calf (p <
      0.001), whilst males exceeded females in head and waist girths (also p < 0.001).
      For a given percentage increase in height, weight and all girths showed greater
      proportional changes in males than females (p < 0.001). DISCUSSION: These results
      indicate sex-specific life history strategies wherein the direction and timing of
      energy investment in girths varies between the sexes. The results add to
      literature suggesting that sexual dimorphism in body morphology is not a fixed
      trait; rather, differential energy allocation to specific body regions appears to
      be a plastic strategy adjusted in relation to energy acquisition across the life
      course.

PMID- 28497850
TI  - Workforce diversity in dentistry - current status and future challenges.
AB  - The racial and ethnic diversity of the US oral health care workforce remains
      insufficient to meet the needs of an increasingly diverse population and to
      address persistent health disparities. The findings from a recent national survey
      of underrepresented minority dentists are reviewed and recommendations are made
      for enhancing diversity in the dental profession.

PMID- 28497851
TI  - A novel mutation in the TYRP1 gene associated with brown coat colour in the
      Australian Shepherd Dog Breed.

PMID- 28497852
TI  - Patients' perception of disease and experience with type 2 diabetes patient
      education in Denmark.
AB  - BACKGROUND: Patient education programmes for a range of chronic conditions are
      widely implemented, but studies have shown that not all participants benefit
      equally from the patient education programmes. AIM: To explore differences in how
      persons with diabetes experience diabetes-related patient education programmes.
      METHODS: Qualitative in-depth interviews were conducted with eleven participants
      6 months after participation in patient education. Using thematic analysis, we
      identified three themes: programme elements, interactions between participants
      and the role of facilitators. We used Alonzo's theory of Everyday Illness
      Behaviour and reported restrictions in daily activities to categorise seven
      participants as 'healthy' and four as 'ill' and compare their experiences of
      patient education. RESULTS: Although all participants identified information on
      diet and exercise as the most beneficial programme element, healthy participants
      found this information easy to understand and apply to make healthy changes in
      their daily lives. Ill participants found the information difficult to understand
      and were much less likely to implement related changes. Healthy participants
      valued social interactions occurring during interactive programme components such
      as weigh-in sessions, physical exercise and cooking classes. In contrast, ill
      participants did not value these social interactions. Healthy participants also
      tended to view programme facilitators more positively. Regardless of disease
      status, participants found it motivating to compare their health status to that
      of participants they perceived as more ill than themselves. CONCLUSION: Patient
      education experiences differ according to self-perceived disease status.
      Programme facilitators should be sensitive to the possibility that participants
      who are more ill may be less likely to perceive patient education as beneficial
      and implement new behaviours. Knowledge about factors leading to differences in
      patient experiences of chronic disease self-management education programmes is
      essential for the development of programmes that benefit all patients. Future
      research should explore the value of programmes differentiated for participants
      with different levels of health.

PMID- 28497853
TI  - Respiratory morbidity among U.S. coal miners in states outside of central
      Appalachia.
AB  - BACKGROUND: Recent NIOSH publications have focused on the respiratory health of
      coal miners in central Appalachia, yet 57% of U.S. coal miners work in other
      regions. We characterized respiratory morbidity in coal miners from these
      regions. METHODS: Active coal miners working outside of central Appalachia who
      received chest radiographs and/or spirometry during 2005-2015 were included.
      Chest radiographs were classified according to International Labour Office
      standards and spirometry was interpreted using the American Thoracic Society
      guidelines. Prevalence of coal workers' pneumoconiosis (CWP) and abnormal
      spirometry were compared by region. RESULTS: A total of 103 (2.1%) miners had
      CWP. The eastern region had the highest prevalence (3.4%), followed by the
      western (1.7%), and interior (0.8%) regions. A total of 524 (9.3%) miners had
      abnormal spirometry. CONCLUSIONS: CWP occurs in all U.S. coal mining regions.
      Prevalence of CWP was higher in the eastern region, but lower than levels
      reported in central Appalachia.

PMID- 28497854
TI  - Allergic sinusitis and severe asthma caused by occupational exposure to locust
      bean gum: Case report.
AB  - We present a case that highlights the difficulties with diagnosis and the dangers
      of occupational allergic sinusitis and asthma left unrecognized. We describe the
      case history of a man who experienced work-related symptoms 1 year after
      beginning work as a cheesemaker at a creamery, and whose respiratory symptoms
      progressively worsened over 16 years before an occupational cause of his asthma
      was identified. His initial discrete episodes of sinusitis and acute bronchitis
      evolved into persistent asthma of increasing severity with exacerbations
      requiring repeated emergency room treatment. The case described in our report
      emphasizes the importance of clinician diagnosis of OA, and subsequent removal
      from exposure, such that asthma severity does not progress to near-fatal or fatal
      asthma in the sensitized worker. As demonstrated by this case report,
      identification of an occupational cause of asthma relies on a high degree of
      suspicion and excellent detective work by the clinician.

PMID- 28497855
TI  - Health promotion for people with intellectual disabilities - A concept analysis.
AB  - BACKGROUND: Whereas 'health promotion' is a well-known concept for healthcare
      professionals, the concept of 'health promotion for people with intellectual
      disabilities' and its unique associated challenges are not well understood. AIMS
      AND OBJECTIVE: This article provides a systematic analysis of how health
      promotion is being conceptualised for people with intellectual disabilities and
      how health promotion can work best in the light of this group's specific needs
      and limitations. DESIGN: Rodgers' evolutionary concept analysis. METHOD: MEDLINE,
      PsycINFO, CINAHL and SocINDEX were searched using the search terms 'health
      promotion', 'people with intellectual disabilities' and 'developmental
      disabilities'. This review includes studies published between 1992 and 2014. A
      total of 52 articles were included. RESULTS: Health promotion for people
      intellectual disabilities, as discussed in the literature, focuses on four
      aspects, namely supporting a healthy lifestyle, providing health education,
      involving supporters and being person-centred. Antecedents of the concept 'health
      promotion for people with intellectual disabilities' were healthcare access and
      sensitised healthcare providers. The outcomes were improved health, being
      empowered, enhanced quality of life and reduced health disparities. CONCLUSION:
      This analysis provides a solid foundation for healthcare stakeholders' planning,
      implementing and evaluating health-promotion activities for people with
      intellectual disabilities at the policy level and in the community.

PMID- 28497856
TI  - Case of shift from linear immunoglobulin A bullous dermatosis to pemphigus
      herpetiformis for a short period of time.
AB  - Pemphigus herpetiformis (PH) is a rare variant of pemphigus characterized by
      erythemas and vesicles, tending to present with annular-shaped lesions.
      Immunologically, immunoglobulin (Ig)G deposition at the keratinocyte cell
      surfaces is observed. Linear IgA bullous dermatosis (LABD) is a rare subepidermal
      blistering disease with linear IgA deposits at the epidermal basement membrane
      zone (BMZ). The annular-shaped skin lesions in PH mimic clinical manifestation of
      other autoimmune bullous diseases, including LABD, although PH and LABD have
      different immunological and histopathological features. Herein, we report the
      first case of a shift from LABD to PH. A 70-year-old Japanese man presented
      annular erythemas surrounded by vesicles on the trunk and extremities.
      Histopathological examination revealed subepidermal bullae and eosinophilic
      spongiosis. Direct immunofluorescence demonstrated linear IgA deposits at the
      epidermal BMZ. Immunoblot analyses of normal human epidermal and dermal extracts,
      supernatant of HaCaT cells, recombinant proteins of BP180 NC16a and C-terminal
      domains, and purified laminin-332 showed no reactivity for either IgG or IgA. IgG
      chemiluminescent enzyme immunoassays for desmogleins 1 and 3, and BP180 were all
      negative. These findings led to the diagnosis of sole LABD. Although oral
      prednisolone temporarily improved the skin lesions, annular erythema without
      vesicles remained. A new skin biopsy revealed subcorneal pustules with
      eosinophils, but no subepidermal bullae. Direct immunofluorescence revealed IgG
      and C3 deposition at the keratinocyte cell surfaces. IgG enzyme-linked
      immunosorbent assay for mammalian desmocollins 1-3 revealed desmocollin 1
      reactivity. Based on these findings, we made a diagnosis of sole PH.

PMID- 28497857
TI  - Validation of electrical ostial pulmonary vein isolation verified with a spiral
      inner lumen mapping catheter during second-generation cryoballoon ablation.
AB  - BACKGROUND: Achieve catheters are cryoballoon guidewires that enable pulmonary
      vein (PV) potential mapping. The single catheter approach in conjunction with the
      Achieve catheter is currently standard practice in second-generation cryoballoon
      ablation, yet circumferential mapping catheters are the gold standard for
      evaluating PV isolation (PVI). The study sought to validate the ostial PVI
      verified by an Achieve catheter alone. METHODS: One hundred fifty-one paroxysmal
      atrial fibrillation patients undergoing PVI using exclusively 28-mm second
      generation cryoballoons were enrolled. PV recordings were analyzed during (real
      time recordings) and after cryoballoon applications with 20-mm Achieve mapping
      catheters, and subsequently validated by 20-mm conventional circumferential
      mapping catheters. RESULTS: Out of 596 PVs, 576 (96.6%) were isolated using
      cryoballoons, and 20 required touch-up ablation. PVI was verified during
      cryoballoon applications with real-time monitoring in 299, and after applications
      in 280 PVs by Achieve catheters alone. The time-to-isolation was 27.2 +/- 22.0
      seconds. Validation with standard circumferential mapping catheters confirmed
      ostial PVIs in 296 of 299 (99.0%) PVs that real-time PVI was obtained during
      applications, and in 242 of 280 (86.5%) PVs that PV activities were not visible
      during applications and PVI was verified after the applications. The accuracy of
      ostial PVIs with Achieve catheters in PVs without obtaining real-time PV
      recordings was 40/47 (85.1%), 58/65 (89.2%), 77/79 (97.5%), 61/81 (75.3%), and
      6/8 (75.0%) in left superior, left inferior, right superior, right inferior, and
      left common PVs, respectively. CONCLUSIONS: In second-generation 28-mm
      cryoballoon ablation, verification of ostial PVIs using Achieve mapping catheters
      alone might not be sufficient to accurately confirm an ostial PVI when real-time
      PVI was not obtained.

PMID- 28497858
TI  - Beat-to-beat ECG restitution: A review and proposal for a new biomarker to assess
      cardiac stress and ventricular tachyarrhythmia vulnerability.
AB  - BACKGROUND: Cardiac restitution is the ability of the heart to recover from one
      beat to the next. Ventricular arrhythmia vulnerability can occur when the heart
      does not properly adjust to sudden changes in rate or in hemodynamics leading to
      excessive temporal and/or spatial heterogeneity in conduction or repolarization.
      Restitution has historically been used to study, by invasive means, the dynamics
      of the relationship between action potential duration (APD) and diastolic
      interval (DI) in sedated subjects using various pacing protocols. Even though the
      analogous measures of APD and DI can be obtained using the surface ECG to acquire
      the respective QT and TQ intervals for ECG restitution, this methodology has not
      been widely adopted for a number of reasons. METHODS: Recent development of more
      advanced software algorithms enables ECG intervals to be measured accurately, on
      a continuous beat-to-beat basis, in an automated manner, and under highly dynamic
      conditions (i.e., ambulatory or exercise) providing information beyond that
      available in the typical resting state. RESULTS: Current breakthroughs in ECG
      technology will allow ECG restitution measures to become a practical approach for
      providing quantitative measures of the risks for ventricular arrhythmias as well
      as cardiac stress in general. CONCLUSIONS: In addition to a review of the
      underlying principles and caveats of ECG restitution, a new approach toward an
      advancement of more integrated restitution biomarkers is proposed.

PMID- 28497859
TI  - Superlubricity between MoS2 Monolayers.
AB  - The ultralow friction between atomic layers of hexagonal MoS2 , an important
      solid lubricant and additive of lubricating oil, is thought to be responsible for
      its excellent lubricating performances. However, the quantitative frictional
      properties between MoS2 atomic layers have not been directly tested in
      experiments due to the lack of conventional tools to characterize the frictional
      properties between 2D atomic layers. Herein, a versatile method for studying the
      frictional properties between atomic-layered materials is developed by combining
      the in situ scanning electron microscope technique with a Si nanowire force
      sensor, and the friction tests on the sliding between atomic-layered materials
      down to monolayers are reported. The friction tests on the sliding between
      incommensurate MoS2 monolayers give a friction coefficient of ~10-4 in the regime
      of superlubricity. The results provide the first direct experimental evidence for
      superlubricity between MoS2 atomic layers and open a new route to investigate
      frictional properties of broad 2D materials.

PMID- 28497860
TI  - Intermittent preexcitation indicates "a low-risk" accessory pathway: Time for a
      paradigm shift?
AB  - We report three patients with intermittent loss of the preexcitation pattern in
      the ECG that had undergone an electrophysiological study. Despite apparently
      poorly conducting accessory pathway (AP), in each case a fast anterograde
      conduction, either during spontaneous atrial fibrillation or during incremental
      atrial pacing (on isoproterenol) was documented; shortest preexcited RR intervals
      of 200-240 ms were observed. We review the literature and conclude that
      intermittent preexcitation observed on resting 12-lead ECG lacks sufficient
      specificity for the diagnosis of an AP with long refractory period and cannot be
      considered a substitute for electrophysiological study in patients with this
      electrocardiographical phenomenon.

PMID- 28497861
TI  - Corticosteroids for preterm deliveries: missing evidence.

PMID- 28497862
TI  - Association between fear of childbirth and maternal acceptance of pregnancy.
AB  - AIM: This descriptive study aimed to explore the associations between fear of
      childbirth, acceptance of pregnancy and identification with the motherhood role
      among primipara women. BACKGROUND: Women who have difficulty accepting their
      pregnancy have a harder time adapting to pregnancy and motherhood and experience
      more fears related to childbirth. The number of studies conducted on this topic
      is limited. METHODS: This study involved 310 pregnant women admitted to a public
      hospital in Istanbul between January and June of 2013. A participant
      identification form, the Prenatal Self-Evaluation Questionnaire and the Wijma
      Delivery Expectancy/Experience Questionnaire Version A were used for data
      collection. RESULTS: Pregnant women participating in the study experienced
      moderate levels fear of childbirth. Pregnant women who requested caesarean
      section experienced more intense fear of childbirth. Fear of childbirth scores
      had significant but weak correlations with acceptance of pregnancy and
      identification with the motherhood role. CONCLUSION: The findings showed that
      acceptance of pregnancy and identification with the motherhood role are weakly
      associated with fear of childbirth. IMPLICATIONS FOR NURSING AND HEALTH POLICY:
      The results from this study can be used to help: increase awareness among health
      professionals (doctors, nurses, midwives) in antenatal care services about a
      mother's adaptation to pregnancy and the negative effects of fear of childbirth;
      direct future research examining factors affecting adaptation to pregnancy and
      fear of childbirth; establish routine assessments for adaptation to pregnancy and
      fear of childbirth; provide professional support for women with difficulties
      adapting to pregnancy and with fear of childbirth; result in reduced
      complications from invasive methods such as caesarean section due to less
      requests for these procedures; and promote the health of mothers and babies.

PMID- 28497864
TI  - Valbenazine for tardive dyskinesia: A systematic review of the efficacy and
      safety profile for this newly approved novel medication-What is the number needed
      to treat, number needed to harm and likelihood to be helped or harmed?
AB  - OBJECTIVE: The objective of this systematic review was to describe the efficacy,
      tolerability, and safety of valbenazine for the treatment of tardive dyskinesia
      (TD). DATA SOURCES: The pivotal registration trials were accessed by querying
      http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the
      search terms 'valbenazine' OR 'NBI-98854', and by also querying the EMBASE
      (Elsevier) commercial database for clinical poster abstracts, and by asking the
      manufacturer for copies of posters presented at congresses. Product labeling
      provided additional information. STUDY SELECTION: All available clinical reports
      of studies were identified. DATA EXTRACTION: Descriptions of the principal
      results and calculation of number needed to treat (NNT) and number needed to harm
      (NNH) for relevant dichotomous outcomes were extracted from the available study
      reports and other sources of information. DATA SYNTHESIS: Valbenazine, a
      reversible inhibitor of Vesicular Monoamine Transporter Type 2 (VMAT2), received
      approval for the treatment of TD in adults based on a clinical trial development
      programme that included three 6-week parallel group, randomised, placebo
      controlled studies, including one Phase III trial described in product labeling.
      The recommended dose for valbenazine is 80 mg/d. The percentage of responders in
      the Phase III acute study, as defined by >=50% reduction from baseline in the
      Abnormal Involuntary Movement Scale dyskinesia score was 40.0% for valbenazine 80
      mg/d vs 8.7% for placebo, yielding a NNT of 4 (95% CI 3-6). As pooled from
      available data, discontinuation rates because of an adverse event were 2.9% for
      valbenazine-treated patients vs 1.6% for placebo-treated patients, resulting in a
      NNH of 76 (ns). The only adverse event that met the threshold of incidence >=5%
      for valbenazine and a rate of >=2 times than that observed with placebo was
      somnolence (somnolence, fatigue, sedation), with rates of 10.9% for valbenazine
      (all doses) vs 4.2% for placebo, resulting in a NNH of 15 (95% CI 9-52). An
      additional warning and precaution is that valbenazine can prolong the ECG QT
      interval, however, the valbenazine product label does not contain any bolded
      boxed warnings or contraindications. CONCLUSIONS: Valbenazine is presently the
      only US Food and Drug Administration-approved agent specifically indicated for
      the treatment of TD. Valbenazine is about 15 times more likely to result in a
      response than in a discontinuation because of an adverse event. Head-to-head
      comparisons with other VMAT2 inhibitors among patients with TD in the 'real
      world' are needed.

PMID- 28497863
TI  - CTLA-4 expressed by FOXP3+ regulatory T cells prevents inflammatory tissue attack
      and not T-cell priming in arthritis.
AB  - Cytotoxic T-lymphocyte antigen 4 (CTLA-4) -mediated regulation of already
      tolerized autoreactive T cells is critical for understanding autoimmune
      responses. Although defects in CTLA-4 contribute to abnormal FOXP3+ regulatory T
      (Treg) cell function in rheumatoid arthritis, its role in autoreactive T cells
      remains elusive. We studied immunity towards the dominant collagen type II (CII)
      T-cell epitope in collagen-induced arthritis both in the heterologous setting and
      in the autologous setting where CII is mutated at position E266D in mouse
      cartilage. CTLA-4 regulated all stages of arthritis, including the chronic phase,
      and affected the priming of autologous but not heterologous CII-reactive T cells.
      CTLA-4 expression by both conventional T (Tconv) cells and Treg cells was
      required but while Tconv cell expression was needed to control the priming of
      naive autoreactive T cells, CTLA-4 on Treg cells prevented the inflammatory
      tissue attack. This identifies a cell-type-specific time window when CTLA-4
      mediated tolerance is most powerful, which has important implications for
      clinical therapy with immune modulatory drugs.

PMID- 28497865
TI  - Predictors and implications of early left ventricular ejection fraction
      improvement in new-onset idiopathic nonischemic cardiomyopathy with narrow QRS
      complex: A NEOLITH substudy.
AB  - BACKGROUND: Predictors and implications of early left ventricular ejection
      fraction (LVEF) improvement with guideline-directed medical therapy (GDMT) in new
      onset idiopathic nonischemic cardiomyopathy (NICM) with narrow QRS complex are
      not well described. The objectives were to describe predictors of LVEF
      improvement after 3 months on GDMT and adverse cardiac events based on post-GDMT
      LVEF status (<=35% vs. >35%). METHODS: A retrospective cohort study was performed
      in subjects with new-onset NICM, LVEF <=35%, and narrow QRS complex. Associations
      for baseline variables with post-GDMT LVEF improvement and absolute change in
      LVEF (?LVEFGDMT ) were assessed. Cox proportional hazards models assessed
      associations for post-GDMT LVEF status with adverse cardiac events. RESULTS: In
      70 subjects, 31 (44%) had post-GDMT LVEF <=35% after a median follow-up time of
      97.5 days (interquartile range, 84-121 days). In final multivariable models,
      severely dilated left ventricular end-diastolic diameter (LVEDD), compared with
      normal LVEDD, strongly predicted post-GDMT LVEF <=35% (odds ratio, 7.77; 95%
      confidence interval [CI], 1.39-43.49; p = .02) and ?LVEFGDMT (beta = -15.709;
      standard error = 4.622; p = .001). Subjects with post-GDMT LVEF <=35% were more
      likely to have adverse cardiac events over a median follow-up time of 970.5 days
      (unadjusted hazard ratio, 2.15; 95% CI, 0.93-4.96; p = .07). In the post-GDMT
      LVEF <=35% group, 9 of 26 subjects (35%) had long-term LVEF > 35%. CONCLUSION: In
      new-onset NICM with narrow QRS complex, nondilated LVEDD predicted early LVEF
      improvement. Those with post-GDMT LVEF <=35% had higher risk of adverse cardiac
      events, but a substantial proportion demonstrated continued long-term LVEF
      improvement.

PMID- 28497866
TI  - Evaluation of a new commercial von Willebrand factor multimer assay.

PMID- 28497867
TI  - The mystery of the missing warbler.

PMID- 28497869
TI  - Increased delta neutrophil index in women with severe preeclampsia.
AB  - PROBLEM: The pathophysiology of preeclampsia (PE) is believed to be associated
      with a systemic inflammatory response, but few inflammatory markers are currently
      available to predict PE. Therefore, the aim of this study was to compare the
      serum delta neutrophil index (DNI) between normal and preeclamptic women.
      METHODS: Sixty-five patients with mild preeclampsia (mPE), 147 patients with
      severe preeclampsia (sPE), and 163 women with normal pregnancy were included in
      this study. Maternal laboratory values including DNI were compared among the
      three groups. RESULTS: The mean DNI was significantly higher in the sPE group,
      but there was no significant difference between the normal pregnancy group and
      mPE. The DNI also showed positive correlation with systolic and diastolic blood
      pressures, mean arterial pressure, proteinuria during 24 hours, proteinuria in
      dipstick, and ominous symptoms. CONCLUSION: The serum DNI value was increased in
      women with severe preeclampsia compared to that in those with normal pregnancy or
      mild preeclampsia. Further studies are needed to evaluate application of the DNI
      value as a prognostic marker of preeclampsia.

PMID- 28497868
TI  - Person-centred care dialectics-Inquired in the context of palliative care.
AB  - Although a widely used concept in health care, person-centred care remains
      somewhat ambiguous. In the field of palliative care, person-centred care is
      considered a historically distinct ideal and yet there continues to be a dearth
      of conceptual clarity. Person-centred care is also challenged by the pull of
      standardization that characterizes much of health service delivery. The
      conceptual ambiguity becomes especially problematic in contemporary pluralistic
      societies, particularly in the light of continued inequities in healthcare access
      and disparities in health outcomes. Our aim was to explicate premises and
      underlying assumptions regarding person-centred care in the context of palliative
      care with an attempt to bridge the apparently competing agendas of
      individualization versus standardization, and individuals versus populations. By
      positioning person-centredness in relation to the hermeneutics of the self
      according to Paul Ricoeur, dialectics between individualization and
      standardization, and between individuals and populations were constructed. The
      competing agendas were related in a dialectic manner in the way that population
      health is of importance for the individual, and standardization is of importance
      for the population. The analysis suggests that person-centred care is an ethical
      stance, which gives prominence to both suffering and capability of the individual
      as a person. The dialectic analysis points towards the importance of extending
      person-centred care to encompass population and societal perspectives and thereby
      avoiding a problematic tendency of affiliating person-centred care with
      exclusively individualistic perspectives. Considerations for person-centred
      palliative care on micro-, meso- and macrolevels conclude the paper.

PMID- 28497870
TI  - Issues in reproductive health in females having inherited bleeding disorders in
      Pakistan.

PMID- 28497872
TI  - Deviant burials and social identity in a postmedieval Polish cemetery: An
      analysis of stable oxygen and carbon isotopes from the "vampires" of Drawsko.
AB  - OBJECTIVES: Deviant burials can reveal important information about both social
      and individual identity, particularly when the mortuary record is supplemented by
      an examination of skeletal remains. At the postmedieval (17th to 18th c. AD)
      cemetery of Drawsko (Site 1), Poland, six individuals (of n = 285) received
      deviant, anti-vampiristic mortuary treatment. A previous study using radiogenic
      strontium isotope ratios ( x-= 0.7112 +/- 0.0006, 1sigma, n = 60) found that
      these "vampires" were in fact locals, not migrants to the region targeted for
      deviant burial due to their status as immigrant outsiders. However, considerable
      geologic overlap in strontium isotope ratios across the North European Plain may
      have masked the identification of at least some nonlocal individuals. This study
      further contextualizes strontium isotope ratios using additional biogeochemical
      data to test the hypothesis that additional nonlocals were present in the Drawsko
      cemetery. METHODS: Stable oxygen and carbon isotopes from the dental enamel of 58
      individuals interred in both normative and atypical burials at Drawsko were
      analyzed. RESULTS: Both delta18 Oc(VPDB) ( x-= -4.5 +/- 0.70/00) and delta13 Cap
      isotope values ( x-= -13.6 +/- 0.80/00) displayed little variability and were not
      significantly different between vampire and normative burials, supporting prior
      strontium results of a largely local population. Nevertheless, homogeneity in
      oxygen isotope values across other northern European sites makes it difficult to
      speculate about isotopic regional diversity, leaving open the possibility that
      additional migrants to the region remain undetected. Additionally, carbon isotope
      values point to a locally sourced diet dominated by C3 resources but with some
      supplementation by C4 goods that likely included millet, fitting with historic
      descriptions of postmedieval diet in Poland. CONCLUSIONS: Those interred as
      vampires appear local to the region and thus likely underwent deviant funerary
      treatment due to some other social stigma not apparent from the skeleton.

PMID- 28497873
TI  - An online education approach to population health in a global society.
AB  - BACKGROUND: Health professions education content must keep pace with the ever
      evolving and changing health care system. Population-based health care is
      advocated as a way to improve health outcomes, particularly in a technologically
      advanced health system like the United States. At the same time, global health
      knowledge is increasingly valued in health professions education, including
      nursing. AIMS: This article describes the design and implementation of an online
      population health course with a global viewpoint intended to accommodate the need
      for improved knowledge and skill application for graduate nurses. Attention was
      also given to faculty efficiency during the process of design and implementation.
      MATERIALS AND METHODS: This population-global health course was piloted in a
      renovated master's curriculum for two semesters. Administering a Course
      Improvement Survey after initial course offerings assisted faculty to assess and
      target essential course changes. Data were collected from 106 registered nurse
      graduate students. RESULTS: Population and global health course objectives were
      met and students identified areas for course enhancement. Students (90%-94%)
      reported achieving increased knowledge of population health and global health.
      DISCUSSION: Like other creative works, the first rendition of a course requires
      pedagogical adjustments and editing. Formal student input, when built into the
      design and implementation of a course can assist faculty to be efficient when
      crafting essential course changes for subsequent semesters. Data from the survey
      showed that major population and global subject matter was being grasped by
      students, the data also revealed that tweaking specific online strategies like
      making all course content mobile would enhance the course. CONCLUSION: The course
      development process and course improvement evaluation for this Population Health
      in a Global Society course proved valuable in the education of nurses, and helped
      maintain faculty work efficiency.

PMID- 28497874
TI  - Serum angiopoietin-2 level as a potential biomarker in psoriasis vulgaris.

PMID- 28497875
TI  - Comparison of the tracheal systems of Anopheles sinensis and Aedes togoi larvae
      using synchrotron X-ray microscopic computed tomography (respiratory system of
      mosquito larvae using SR-MUCT).
AB  - Mosquito-borne diseases, such as malaria, dengue fever, and Zika virus, are
      serious global health issues. Vector control may be an important strategy in
      reducing the mortality caused by these diseases. The respiratory system of
      mosquito larvae in the water has to inhale atmospheric oxygen as aquatic
      organisms. In this study, the three-dimensional (3D) structures of the dorsal
      longitudinal trunks (DLTs) of the tracheal systems of Anopheles sinensis and
      Aedes togoi were compared using synchrotron X-ray microscopic computed
      tomography. DLT respiratory frequencies were also investigated. Interestingly,
      the larvae of the two mosquito species exhibit tracheal systems that are both
      morphologically and functionally distinct. A. sinensis hangs horizontally under
      the water surface, and has a smaller DLT volume than A. togoi. In contrast, A.
      togoi hangs upside down using a siphon by fixing its tip to the water surface.
      The frequency of peristaltic movement in A. togoi is higher than that of A.
      sinensis. These differences in the structures and breathing behaviors of the
      respiratory systems of mosquito larvae provide new insights into the tracheal
      systems of mosquito larvae, which should help develop novel effective control
      strategies targeting mosquito larvae.

PMID- 28497876
TI  - Morphological variations on microscopy in oocysts of coccidian parasites: A
      prospective study from a tertiary care hospital in north India.
AB  - The modified acid fast staining technique is a commonly used procedure for the
      detection of coccidian parasites in developing countries. The morphological
      variations observed in these parasites play a significant role to some extent in
      both identification and diagnosis of these parasitic infections. A prospective
      cross sectional study was performed over three years. The fecal smears were
      stained by modified Kinyoun acid-fast staining technique and were extensively
      studied for morphological variations in the coccidian parasites. Out of a total
      of two thousand one hundred fifty one (n = 2,151) fecal samples received during
      the study period, 259 samples (12%) were positive for any one of the coccidian
      parasites. Morphological variations, especially in the staining character was
      noted in all the three coccidian parasites. This study was an attempt to
      characterize different variations in size, shape and staining characteristics of
      the three coccidian parasites.

PMID- 28497877
TI  - Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's
      disease.
AB  - Spinal cord stimulation has been used for the treatment of chronic pain for
      decades. In 2009, our laboratory proposed, based on studies in rodents, that
      electrical stimulation of the dorsal columns of the spinal cord could become an
      effective treatment for motor symptoms associated with Parkinson's disease (PD).
      Since our initial report in rodents and a more recent study in primates, several
      clinical studies have now described beneficial effects of dorsal column
      stimulation in parkinsonian patients. In primates, we have shown that dorsal
      column stimulation activates multiple structures along the somatosensory pathway
      and desynchronizes the pathological cortico-striatal oscillations responsible for
      the manifestation of PD symptoms. Based on recent evidence, we argue that
      neurological disorders such as PD can be broadly classified as diseases emerging
      from abnormal neuronal timing, leading to pathological brain states, and that the
      spinal cord could be used as a "channel" to transmit therapeutic electrical
      signals to disrupt these abnormalities. (c) 2017 International Parkinson and
      Movement Disorder Society.

PMID- 28497878
TI  - Pharmacist prescribing: a cross-sectional survey of the views of pharmacists in
      Nigeria.
AB  - OBJECTIVES: This study was carried out to: (1) explore the views of pharmacists
      in Nigeria on the extension of prescribing authority to them and determine their
      willingness to be prescribers and (2) identify the potential facilitators and
      barriers to introducing pharmacist prescribing in Nigeria. METHOD: An online
      cross-sectional survey was conducted from August to October 2014 among 775
      pharmacists recruited from the Facebook group of the Pharmaceutical Society of
      Nigeria using a simple random technique. The questionnaire used for the survey
      was developed based on the review of the literature and previous qualitative
      studies conducted in Nigeria. The instrument was evaluated for content validity
      by two external pharmacy practice researchers and the reliability of items
      assessed using internal consistency tests. Data obtained from the survey were
      entered into SPSS v.22, and descriptive statistics were generated. Relationships
      between variables were evaluated using the chi-square test, and P < 0.05 was
      considered statistically significant. KEY FINDINGS: The response rate was 40.6%
      (315/775). Three hundred and six (97.1%) respondents agreed that pharmacists
      should be given prescribing authority. Of these 306, 295 (96.4%) were willing to
      be prescribers, and just over half of them (148/295; 50.2%) would prefer to
      prescribe in collaboration with medical doctors. Of those willing to be
      prescribers, 285 (96.6%) reported that they would need additional training. The
      most perceived areas of training needed were in the principles of differential
      diagnosis (81.4%), pathophysiology of diseases (74.0%) and interpretation of
      laboratory results (68.1%). Respondents identified increasing patients' access to
      care (308/315; 97.8%) and better utilisation of pharmacists' skills (307/315;
      97.5%) as the most likely facilitators to pharmacist prescribing in Nigeria. On
      the other hand, resistance from the medical doctors (299/315; 94.9%) and
      pharmacists' inadequate skills in diagnosis (255/315; 81.0%) were perceived as
      the most likely barriers. CONCLUSION: Pharmacist prescribing represents an
      opportunity to promote patients' access to care and the utilisation of
      pharmacists' skills in Nigeria. The majority of pharmacists showed a positive
      attitude towards pharmacist prescribing and were willing to be prescribers. The
      findings of this study could potentially contribute to future medicine
      prescribing policy and pharmacy practice in Nigeria.

PMID- 28497879
TI  - Bone morphogenetic protein-5, a key molecule that mediates differentiation in
      MC3T3E1 osteoblast cell line.
AB  - Bone morphogenetic protein-5 (BMP-5) is a member of the TGF receptor-beta family
      with osteoinductive property. However, its physiological role in osteoblast
      differentiation is not defined. This study highlights the importance of BMP-5 in
      MC3T3E1 osteoblast differentiation. Pre-osteoblasts exposed to osteogenic media
      (ascorbic acid, 50 ug/ml and beta-glycerophosphate, 10 mM) showed high protein
      expression of BMP-5 in cell lysates and cell culture supernatants, which peaked
      during early time-points of differentiation and declined with onset of
      mineralization. Attenuation of endogenous BMP-5 protein expression by RNA
      interference downregulated the expression of type I collagen (COLIA1), an early
      osteoblast differentiation marker but not osteocalcin, a late osteoblast
      differentiation marker. Further experiments to analyze the cell signaling
      components revealed that BMP-5 modulates COLIA1 expression via p38-Runx2 axis
      involving Runx2 (Ser19) phosphorylation. These effects were also observed when
      recombinant BMP-5 was added to pre-osteoblast cultures reinforcing the fact that
      BMP-5 is a modulator of COLIA1 expression. We conclude that BMP-5 has stage
      specific role to play during MC3T3E1 osteoblast differentiation in part by
      autocrine p38/Runx2/COLIA1 signaling. (c) 2017 BioFactors, 43(4):558-566, 2017.

PMID- 28497880
TI  - Ambient Protection of Few-Layer Black Phosphorus via Sequestration of Reactive
      Oxygen Species.
AB  - Few-layer black phosphorous (BP) has emerged as a promising candidate for next
      generation nanophotonic and nanoelectronic devices. However, rapid ambient
      degradation of mechanically exfoliated BP poses challenges in its practical
      deployment in scalable devices. To date, the strategies employed to protect BP
      have relied upon preventing its exposure to atmospheric conditions. Here, an
      approach that allows this sensitive material to remain stable without requiring
      its isolation from the ambient environment is reported. The method draws
      inspiration from the unique ability of biological systems to avoid photo
      oxidative damage caused by reactive oxygen species. Since BP undergoes similar
      photo-oxidative degradation, imidazolium-based ionic liquids are employed as
      quenchers of these damaging species on the BP surface. This chemical
      sequestration strategy allows BP to remain stable for over 13 weeks, while
      retaining its key electronic characteristics. This study opens opportunities to
      practically implement BP and other environmentally sensitive 2D materials for
      electronic applications.

PMID- 28497881
TI  - Efficacy of intrauterine perfusion of granulocyte colony-stimulating factor (G
      CSF) for Infertile women with thin endometrium: A systematic review and meta
      analysis.
AB  - This meta-analysis aimed to explore the efficiency of intrauterine perfusion of
      granulocyte colony-stimulating factor (G-CSF) on infertile women with thin
      endometrium. Following PRISMA protocol, we conducted a comprehensive search of
      academic literatures on various databases including PubMed, EMbase, and Cochrane
      Library. Studies published in English before July 1, 2016 were included for
      primary screening. Data on the thickness of endometrium, cycle cancelation
      rate,clinical pregnancy rate, and embryo implantation rate were extracted and
      analyzed, respectively. Eleven eligible studies involving 683 patients were
      included in this meta-analysis. Compared with control group, G-CSF perfusion
      could significantly improve endometrial thickness (mean difference [MD]=1.79, 95%
      confidence interval (CI): 0.92-2.67), clinical pregnancy rate (risk ratio
      [RR]=2.52, 95% CI: 1.39-4.55), and embryo implantation rate (RR=2.35, 95% CI:
      1.20-4.60), while it could decrease cycle cancelation rate (RR=0.38, 95% CI: 0.25
      0.58). Funnel plots revealed that there was no evidence of publication bias. The
      current data indicate that intrauterine perfusion of G-CSF can improve
      endometrial thickness, clinical pregnancy rate, and embryo implantation rate, but
      decrease the cycle cancelation rate in women with thin endometrium.

PMID- 28497882
TI  - Identification of the 2-tridecanone cis-acting element in the promoter of
      cytochrome P450 CYP6B7 in Helicoverpa armigera.
AB  - The expression level of cytochrome P450 genes in insects can be induced by plant
      allelochemicals, which is important for insects to adapt to host plants.
      Cytochrome P450 CYP6B7 has been reported to be involved in pyrethroid insecticide
      resistance in Helicoverpa armigera, and its transcription level was induced by
      some inducers. Currently, the regulatory mechanism of the induced expression of
      CYP6B7 remains unknown, although it is very important for understanding the
      detoxification mechanism to allelochemicals in host plants. The objective of the
      present study was to investigate the cis-acting element in the promoter of CYP6B7
      mediating the inducible up-regulation of CYP6B7 in H. armigera by 2-tridecanone.
      The promoter region of CYP6B7 was cloned by genome walking technique and analyzed
      by transient transfection assay. Progressive 5' deletion of the promoter region
      of CYP6B7 revealed that the relative luciferase activity of construct -320/+232
      could be significantly induced by 2-tridecanone. Further stepwise deletion
      between -320 and -238 bp found that construct -292/+232 could also be
      significantly induced by 2-tridecanone, but the adjacent construct -256/+232
      could not, suggesting the essential role of the sequence between -292 and -257 bp
      for 2-tridecanone induction. Nucleotide mutations between -292 and -281 bp had no
      influence on the induction effect by 2-tridecanone, but nucleotide mutations
      between -280 and -257 bp significantly decreased the induction effect. These
      results demonstrated that the cis-acting element for 2-tridecanone induction was
      between -280 and -257 bp in the promoter of CYP6B7.

PMID- 28497883
TI  - Laser-Induced Graphene in Controlled Atmospheres: From Superhydrophilic to
      Superhydrophobic Surfaces.
AB  - The modification of graphene-based materials is an important topic in the field
      of materials research. This study aims to expand the range of properties for
      laser-induced graphene (LIG), specifically to tune the hydrophobicity and
      hydrophilicity of the LIG surfaces. While LIG is normally prepared in the air,
      here, using selected gas atmospheres, a large change in the water contact angle
      on the as-prepared LIG surfaces has been observed, from 0 degrees 
      (superhydrophilic) when using O2 or air, to >150 degrees  (superhydrophobic) when
      using Ar or H2 . Characterization of the newly derived surfaces shows that the
      different wetting properties are due to the surface morphology and chemical
      composition of the LIG. Applications of the superhydrophobic LIG are shown in
      oil/water separation as well as anti-icing surfaces, while the versatility of the
      controlled atmosphere chamber fabrication method is demonstrated through the
      improved microsupercapacitor performance generated from LIG films prepared in an
      O2 atmosphere.

PMID- 28497884
TI  - Catalytic Enantioselective Arylation and Heteroarylation of Ketones with
      Organotitanium Reagents Generated In Situ.
AB  - A practical and useful, catalytic enantioselective method has been developed for
      the synthesis of tertiary diaryl and aryl heteroaryl carbinols starting from
      commercially available aromatic ketones and aryl or heteroaryl bromides. In this
      method, organotitanium reagents are generated in situ from the bromides by
      lithiation with nBuLi followed by transmetallation of the resulting
      organolithiums with ClTi(OiPr)3 . Treatment of the ketones with the titanium
      reagents in the presence of (R)-3-(3,5-bistrifluoromehthylphenyl)-1,1'-bi-2
      naphthol (BTFP-BINOL) affords the corresponding tertiary alcohols in high
      enantioselectivities and yields. The reaction can also start with furan and 2
      thienyllithium. The method is operationally simple and can be conducted on a 10
      mmol scale without any difficulties.

PMID- 28497886
TI  - Acquired von Willebrand syndrome in haematologic malignancies - how the clinical
      laboratory correlation improves a challenging diagnosis - a case series.

PMID- 28497885
TI  - Larval interference competition between the native Neotropical mosquito Limatus
      durhamii and the invasive Aedes aegypti improves the fitness of both species.
AB  - Interspecific competition with native species during biological invasions can
      sometimes limit alien expansion. We aimed to determine the potential ecological
      effects of Limatus durhamii Theobald 1901, a native Neotropical mosquito
      (Diptera: Culicidae) species, on the invasive species Aedes (Stegomyia) aegypti
      (Linnaeus 1762) that breeds in the same artificial water containers. Development
      time and adult dry mass were measured in 3 rearing conditions: control (a single
      larva), intraspecific competition (2 conspecific larvae), and interspecific
      competition (2 heterospecific larvae). Food was provided ad libitum to eliminate
      exploitative competition. For Ae. aegypti, development time was not affected by
      interspecific interference competition (nonsignificant differences with the
      control) and the adult dry mass was significantly higher, meaning that individual
      fitness likely increased. Yet, because previous studies showed longer development
      time and lighter adults during competition with other invasive mosquitoes, it is
      likely that Ae. aegypti can express a different phenotype depending on the
      competing species. The similar pattern found for Li. durhamii females and the
      nonsignificant difference with the control for males explain in part why this
      species can compete with Ae. aegypti.

PMID- 28497887
TI  - Surviving moment to moment: The experience of living in a state of ambivalence
      for those with recurrent suicide attempts.
AB  - OBJECTIVE: This qualitative study aimed to capture the experience of living in
      the ambivalent space between life and death for adults with recurrent suicide
      attempts (RSA). It sought to expand upon an earlier study that explored the
      processes involved in transitioning away from RSA among adults, which revealed
      that occupying this ambivalent space is a crucial part of this process. DESIGN:
      Interpretive phenomenological analysis (IPA) was used. This methodology was
      designed to explore the lived experiences and meaning making and enabled
      interpretation of the multidimensional subjective experiences of RSA
      participants. METHODS: In-depth semi-structured interviews were conducted with
      eight adult women with a history of RSA who had participated in a therapeutic
      intervention at the research site (Skills for Safer Living: A
      Psychosocial/Psychoeducational Intervention for People with Recurrent Suicide
      Attempts [SfSL/PISA]). The six stages of IPA were followed to analyse the
      interview data. RESULTS: Analysis revealed the superordinate theme, 'surviving
      moment to moment', which refers to a precarious state of making decisions about
      one's life and destiny on a moment-to-moment basis without clear commitment to
      either life or death. Two subordinate themes were identified: 'deciding not to
      die in the moment' when the participants were more invested in dying than living
      and 'deciding to live in the moment' when they were more invested in living than
      dying. CONCLUSION: The study illuminated the complex process of making decisions
      about ones' destiny on a moment-to-moment basis. It revealed the torment
      experienced when occupying this state, while paradoxically, also revealing how
      indecision about life and death provided a lifeline opportunity for those with
      RSA. Clinicians who recognize the subtle distinctions associated with this in
      between state can tailor their interventions accordingly. PRACTITIONER POINTS:
      Surviving moment to moment is characterized by a state of emotional flux and
      uncertainty about one's destiny, where the person has not fully committed to
      either life or death. Within this state, there are two interlinked subprocesses,
      whereby the person is leaning more towards death or life. A critical feature in
      working with this client group is to recognize their ambiguity and the fragility
      and temporality of their decisions about their destiny. The practitioner has an
      opportunity to be a catalyst in the momentum towards life by demonstrating
      understanding of this survival struggle and tailoring intervention to fit with
      the nuanced processes within this state.

PMID- 28497888
TI  - Gender equity imbalance in electrocardiology: A call to action.

PMID- 28497889
TI  - Selective Separation of Aliphatic Nitriles by Employing a Two-Dimensional
      Interdigitated Coordination Polymer.
AB  - A room-temperature slow diffusion reaction of the metal nitrates [M=ZnII and CoII
      ] with 5-azido isophthalic acid (AIPA) and 1,4-bis(4-pyridyl)-2,3-diaza-1,3
      butadiene (BPDB) resulted in a new two-dimensional interdigitated coordination
      polymer, [M(C8 H3 N3 O4 )(C12 H10 N4 )]?DMF [DMF=dimethyl formamide (C3 H7 NO)].
      The non-bonded DMF molecules were found to exchange through a single-crystal to
      single-crystal (SCSC) fashion with many aliphatic nitrile compounds. More
      importantly, the present compound, I?DMF(Zn) appears to absorb cis-crotononitrile
      selectively from the cis/trans mixture as well as a mixture containing the
      structural isomer (allylnitrile). It also preferentially absorbs propionitrile
      from an equimolar mixture of acetonitrile, propionitrile, and butyronitrile
      (1:2:1). The cobalt compound exhibits anti-ferromagnetic behavior.

PMID- 28497890
TI  - Direct Asymmetric Alkylation of Ketones: Still Unconquered.
AB  - The alkylation of ketones is taught at basic undergraduate level. In many cases
      this transformation leads to the formation of a new stereogenic center. However,
      the apparent simplicity of the transformation is belied by a number of problems.
      So much so, that a general method for the direct asymmetric alkylation of ketones
      remains an unmet target. Despite the advancement of organocatalysis and
      transition-metal catalysis, neither field has provided an adequate solution.
      Indeed, even use of an efficient and general stoichiometric chiral reagent has
      yet to be reported. Herein we describe the state-of-the-art in terms of direct
      alkylation reactions of some carbonyl groups. We outline the limited progress
      that has been made with ketones, and potential routes towards ultimately
      achieving a widely applicable methodology for the asymmetric alkylation of
      ketones.

PMID- 28497892
TI  - Echoes of others: A path analytic examination of an interpersonal-cognitive model
      of voice-related distress.
AB  - OBJECTIVES: Cognitive models propose that levels of distress associated with
      auditory verbal hallucinations ('voices') are influenced by the hearers' beliefs
      about their voices (perceived malevolence and omnipotence), their negative
      beliefs about themselves and others and their attachment style. This study aims
      to test a comprehensive model of the relationship between these variables in
      order to identify distal and proximal interpersonal and cognitive factors
      contributing to voice-related distress. This interpersonal-cognitive model of
      voices proposes that attachment anxiety/avoidance drive negative beliefs about
      self and others, which in turn lead to persecutory (malevolent/omnipotent)
      beliefs about voices, which in turn increase levels of voice-related distress.
      DESIGN/METHODS: Path analysis was used to test the interpersonal-cognitive model
      in a sample of 180 people currently hearing voices (57% self-reported
      schizophrenia-spectrum diagnoses; 90% some form of self-reported mental health
      diagnosis). RESULTS: Path analysis provided support for a model in which there
      were direct pathways from attachment anxiety and avoidance to negative beliefs
      about self and others; direct pathways from negative beliefs about self and
      others to persecutory beliefs about voices; and a direct path from persecutory
      beliefs about voices, and negative beliefs about self, to voice distress.
      CONCLUSIONS: Findings add support to the suggestion that voice-related distress
      occurs in the context of an insecure attachment style and negative core beliefs
      about self/others. A therapeutic focus on beliefs about voices, attachment style
      and core beliefs about self/others may be important to minimize voice-related
      distress. Further tests of this model that can establish causal relationships
      between variables are now needed. PRACTITIONER POINTS: Distress associated with
      auditory verbal hallucinations ('voices') is highly variable. This study tests a
      comprehensive interpersonal-cognitive model of voice distress using path analysis
      with 180 participants. The model tested in the current paper shows that
      attachment style predicts negative beliefs about self and others, which in turn
      predicts negative beliefs about voices, which in turn predicts voice-related
      distress. Findings support the suggestion that voice-related distress occurs in
      the context of an insecure attachment style and negative core beliefs about self
      and others. In addition to focusing on beliefs about voices, a therapeutic focus
      on attachment style and core beliefs about self and others may be important in
      order to minimize voice-related distress.

PMID- 28497891
TI  - Does adenomatous polyposis coli gene promoter 1A methylation increase non-small
      cell lung cancer risk? A meta-analysis.
AB  - BACKGROUND: The promoter region of the adenomatous polyposis coli (APC) gene is
      hypermethylated in several types of cancers, including non-small cell lung cancer
      (NSCLC). The prevalence of methylation in the promoter region of this gene in
      tumor tissues and autologous controls has not been consistent in previous
      studies. We evaluated the frequency of APC gene promoter 1A methylation between
      tumor tissues and autologous controls in NSCLC patients by meta-analysis.
      METHODS: Open published studies of APC gene promoter 1A methylation between tumor
      tissues and autologous samples in NSCLC patients were identified using a
      systematic search. Odds ratios (OR) and 95% confidence intervals (CI) of APC gene
      promoter 1A methylation in lung cancer tissues versus autologous controls were
      calculated. Fourteen studies, involving a total of 1345 patients and 2182
      samples, were finally included. RESULTS: The pooled proportion of APC promoter 1A
      methylation was 0.62 (95% CI 0.52-072) and 0.34 (95% CI 0.21-0.50) in cancer
      tissues and autologous controls, respectively. The APC gene promoter 1A
      methylation rate in cancer tissues was much higher than in autologous controls,
      with a pooled OR of 3.66 (95% CI 2.12-6.33). A strong and significant correlation
      of APC gene promoter 1A methylation between tumor tissues and autologous controls
      was detected (correlation coefficient rpearson  = 0.77; P  = 0.0013). CONCLUSION:
      The proportion of APC promoter 1A methylation in lung cancer tissues was higher
      than in autologous controls, indicating that promoter 1A methylation of the APC
      gene may play an important role in NSCLC carcinogenesis.

PMID- 28497893
TI  - The 4Kscore blood test accurately identifies men with aggressive prostate cancer
      prior to prostate biopsy with or without DRE information.
AB  - INTRODUCTION: The 4Kscore Test is a prebiopsy blood test that incorporates four
      prostate protein biomarkers along with patient clinical information to determine
      a man's risk for high-grade, aggressive (Gleason >=7) prostate cancer. However,
      some men likely to benefit from the test may be seen in primary care settings
      where the digital rectal examination (DRE) information is not always obtained. In
      this study, we assessed the clinical validity of the 4Kscore Test when the DRE
      information was not included in the algorithm. METHODS: The Prospective 4Kscore
      Validation Study enrolled 1012 men scheduled for prostate biopsy across 26
      urology practices in the United States. The 4Kscore was calculated for each
      patient with and without DRE information. The primary outcome was Gleason >=7
      prostate cancer on prostate biopsy. The contribution of DRE to the predictive
      accuracy of the test was evaluated by area under the receiver operating curve
      (AUC-ROC), risk calibration and clinical consequences. RESULTS: High-grade,
      aggressive prostate cancer was found in 231 (23%) of the 1012 patients. Both
      versions of the 4Kscore Test, with and without DRE, showed excellent
      discrimination (AUC=0.821 with DRE and AUC=0.818 without DRE input) and excellent
      calibration. No clinically significant difference was found between the two
      versions of the 4Kscore. CONCLUSIONS: The 4Kscore Test algorithm, whether DRE
      findings are available or not, performs well in predicting a man's risk of high
      grade, aggressive prostate cancer. Patients who are suspected of having
      aggressive prostate cancer can safely have their risk better defined by 4Kscore
      even if a DRE has not been performed recently.

PMID- 28497894
TI  - Sensor-based gait analysis as a simple tool to measure gait in haemophilia
      patients.

PMID- 28497895
TI  - In the face of pain: The choice of visual cues in pain conditioning matters.
AB  - BACKGROUND: Visual cue conditioning is a valuable experimental paradigm to
      investigate placebo and nocebo effects in pain. However, little attention has
      been paid to the cues themselves and potential variability of effects (their
      quantity and quality) stemming from the choice of stimuli. Yet, this seemingly
      methodological question has important implications for the interpretation of
      experimental findings in terms of their significance for clinical practice.
      METHODS: We investigated the effect of heat pain conditioning using different
      types of visual cues (abstract images, faces and pseudo-words) in a group of 22
      healthy volunteers. We analysed conditioning effects calculated as the difference
      in pain ratings to heat stimuli of identical temperature preceded by conditioned
      high or low pain cues with (1) subliminal and supraliminal presentation; and (2)
      immediately after conditioning and following extinction. Awareness manipulation
      and test following indirect, observational extinction allowed us to assess the
      strength and robustness of the conditioning effects induced with different cue
      types. RESULTS: We observed no differences in conditioning effect magnitudes
      between images, faces and words when all stimuli were presented supraliminally.
      With subliminal presentation, only face stimuli elicited a significant effect;
      equally only face cue-induced effect withstood extinction. CONCLUSIONS: Our
      findings indicate that face-related associations to pain might be stronger than
      those elicited with other visual cues, as face cues seem to induce stronger
      subliminal effects and withstand mild extinction. SIGNIFICANCE: We compared
      different types of neutral cues commonly used in conditioning paradigms and found
      that faces elicited a stronger, more robust nonconscious effect than abstract
      images or pseudo-words.

PMID- 28497896
TI  - Self-Assembled Au/CdSe Nanocrystal Clusters for Plasmon-Mediated Photocatalytic
      Hydrogen Evolution.
AB  - Plasmon-mediated photocatalytic systems generally suffer from poor efficiency due
      to weak absorption overlap and thus limited energy transfer between the plasmonic
      metal and the semiconductor. Herein, a near-ideal plasmon-mediated photocatalyst
      system is developed. Au/CdSe nanocrystal clusters (NCs) are successfully
      fabricated through a facile emulsion-based self-assembly approach, containing Au
      nanoparticles (NPs) of size 2.8, 4.6, 7.2, or 9.0 nm and CdSe quantum dots (QDs)
      of size ~3.3 nm. Under visible-light irradiation, the Au/CdSe NCs with 7.2 nm Au
      NPs afford very stable operation and a remarkable H2 -evolution rate of 73  mmol 
      gCdSe-1 h-1 (10* higher than bare CdSe NCs). Plasmon resonance energy transfer
      from the Au NPs to the CdSe QDs, which enhances charge-carrier generation in the
      semiconductor and suppresses bulk recombination, is responsible for the
      outstanding photocatalytic performance. The approach used here to fabricate the
      Au/CdSe NCs is suitable for the construction of other plasmon-mediated
      photocatalysts.

PMID- 28497897
TI  - Expression profile of heat shock proteins in placental tissues of patients with
      preterm prelabor rupture of membranes and spontaneous preterm labor with intact
      membranes.
AB  - PROBLEM: Investigating the stress response in the central cotyledon zone of
      placental tissue in pregnancies with PPROM, PTB, and at term in labor. METHOD OF
      STUDY: Gene expression of Hsp27, Hsp60, Hsp70, Hsp90, and HspBP1 was compared
      between these particular groups. Correlation between variables including Hsp gene
      expression in placental tissue and the gestational age at delivery, WBC count at
      admission, and serum levels of CRP at admission in patients with PPROM and PTB
      was determined. RESULTS: Both PPROM and PTB pregnancies were associated with
      altered Hsp gene expression profile. While PPROM and PTB always induced
      upregulation of Hsp27 and Hsp60, downregulation of Hsp70 and HspBP1 was present
      entirely in patients with PPROM. HspBP1 expression profile was also able to
      differentiate between PPROM and PTB pregnancies. The highest mRNA levels of Hsp60
      and Hsp70 were detected in PTB pregnancies with elevated CRP levels at admission.
      Some of the examined Hsp displayed increased expression with advancing
      gestational age in both groups (PPROM: Hsp27, Hsp70, and Hsp90; and PTB: Hsp27).
      CONCLUSION: Upregulation of Hsp27 is a common phenomenon shared between
      pregnancies affected with PTB and PPROM. On the other hand, downregulation of
      Hsp70 and HspBP1 represents a unique feature of PPROM.

PMID- 28497898
TI  - Additional cytogenetic abnormalities and variant t(9;22) at the diagnosis of
      childhood chronic myeloid leukemia: The experience of the International Registry
      for Chronic Myeloid Leukemia in Children and Adolescents.
AB  - BACKGROUND: In the adult population with newly diagnosed chronic myeloid leukemia
      (CML), variant translocations are usually not considered to be impairing the
      prognosis, whereas some additional cytogenetic abnormalities (ACAs) are
      associated with a negative impact on survival. Because of the rarity of CML in
      the pediatric population, such abnormalities have not been investigated in a
      large group of children with CML. METHODS: The prognostic relevance of variant
      t(9;22) and ACAs at diagnosis was assessed in 301 children with CML in the
      chronic phase who were enrolled in the International Registry for Chronic Myeloid
      Leukemia in Children and Adolescents. RESULTS: Overall, 19 children (6.3%)
      presented with additional cytogenetic findings at diagnosis: 5 children (1.7%)
      had a variant t(9;22) translocation, 13 children (4.3%) had ACAs, and 1 had both.
      At 3 years, for children with a classic translocation, children with ACAs, and
      children with a variant t(9;22) translocation who were treated with imatinib as
      frontline therapy, the probability of progression-free survival (PFS) was 95%
      (95% confidence interval [CI], 91%-97%), 100%, and 75% (95% CI, 13%-96%),
      respectively, and the probability of overall survival (OS) was 98% (95% CI, 95%
      100%), 100% (95% CI, 43%-98%), and 75% (95% CI, 13%-96%), respectively. No
      statistical difference was observed between the patients with classic cytogenetic
      findings and those with additional chromosomal abnormalities in terms of PFS and
      OS. CONCLUSIONS: In contrast to adults with CML, additional chromosomal
      abnormalities observed at diagnosis do not seem to have a significant prognostic
      impact. Cancer 2017;123:3609-16. (c) 2017 American Cancer Society.

PMID- 28497900
TI  - Utility and reliability of non-invasive muscle function tests in high-fat-fed
      mice.
AB  - NEW FINDINGS: What is the central question of this study? Non-invasive muscle
      function tests have not been validated for use in the study of muscle performance
      in high-fat-fed mice. What is the main finding and its importance? This study
      shows that grip strength, hang wire and four-limb hanging tests are able to
      discriminate the muscle performance between chow-fed and high-fat-fed mice at
      different time points, with grip strength being reliable after 5, 10 and 20 weeks
      of dietary intervention. Non-invasive tests are commonly used for assessing
      muscle function in animal models. The value of these tests in obesity, a
      condition where muscle strength is reduced, is unclear. We investigated the
      utility of three non-invasive muscle function tests, namely grip strength (GS),
      hang wire (HW) and four-limb hanging (FLH), in C57BL/6 mice fed chow (chow group,
      n = 48) or a high-fat diet (HFD group, n = 48) for 20 weeks. Muscle function
      tests were performed at 5, 10 and 20 weeks. After 10 and 20 weeks, HFD mice had
      significantly reduced GS (in newtons; mean +/- SD: 10 weeks chow, 1.89 +/- 0.1
      and HFD, 1.79 +/- 0.1; 20 weeks chow, 1.99 +/- 0.1 and HFD, 1.75 +/- 0.1), FLH
      [in seconds per gram body weight; median (interquartile range): 10 weeks chow,
      2552 (1337-4964) and HFD, 1230 (749-1994); 20 weeks chow, 2048 (765-3864) and
      HFD, 1036 (717-1855)] and HW reaches [n; median (interquartile range): 10 weeks
      chow, 4 (2-5) and HFD, 2 (1-3); 20 weeks chow, 3 (1-5) and HFD, 1 (0-2)] and
      higher falls [n; median (interquartile range): 10 weeks chow, 0 (0-2) and HFD, 3
      (1-7); 20 weeks chow, 1 (0-4) and HFD, 8 (5-10)]. Grip strength was reliable in
      both dietary groups [intraclass correlation coefficient (ICC) = 0.5-0.8; P <
      0.05], whereas FLH showed good reliability in chow (ICC = 0.7; P < 0.05) but not
      in HFD mice after 10 weeks (ICC < 0.5). Our data demonstrate that non-invasive
      muscle function tests are valuable and reliable tools for assessment of muscle
      strength and function in high-fat-fed mice.

PMID- 28497899
TI  - Replacing warfarin with a novel oral anticoagulant: Risk of recurrent bleeding
      and stroke in patients with warfarin ineligible or failure in patients with
      atrial fibrillation (The ROAR study).
AB  - BACKGROUND: A significant proportion of patients treated with warfarin for atrial
      fibrillation (AF) become warfarin ineligible (WI) due to major bleeding events
      (MBE) or systemic thromboembolism (STE). We report a large multicenter real-world
      experience of the use of direct oral antagonists (DOACs) in these WI patients.
      METHODS: We report the outcomes of 263 WI patients treated with DOACs. The
      primary objective was to evaluate clinical outcomes of STE and MBE with DOACs.
      Secondary objective was to assess clinical predictors of repeat MBE and STE on
      DOACs. RESULTS: Note that 63% (166 of 263) patients had a repeat MBE on DOACs.
      Repeat MBE was significantly higher in patients with prior gastrointestinal
      bleeding (74.5% vs. 30%, P < 0.0001). Five percent (12 of 263) developed repeat
      STE. Higher mean CHA2DS2VASC (6.5 +/- 1.7 vs. 3.3 +/- 1.6 = 0.001) score was
      associated with repeat STE. About 34% (57 of 166) of patients had an intervention
      to manage repeat MBE. LAAO devices were successfully used in 67% (12 of 18) high
      risk patients who underwent major interventions to manage MBE. CONCLUSION: In WI
      patients rechallenged with DOACs, a significant proportion developed repeat MBE.
      LAAO devices seem reasonable in those patients who undergo major interventions to
      manage MBE with cautious and temporary continuation of DOAC.

PMID- 28497901
TI  - Risk factors of periodontal disease in Vietnamese patients.
AB  - AIM: The aim of the present study was to assess the association of periodontitis
      with dental and smoking behaviors, self-perception of oral status, dental
      knowledge, and obesity in Vietnamese patients. METHODS: A cross-sectional study
      was conducted on 367 adults who first visited the Faculty of Odonto-Stomatology,
      University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. Information on
      demographic characteristics, dental and smoking behaviors, self-perception of
      oral status, dental knowledge, and nutritional status was investigated by a self
      administered questionnaire. Periodontal status, including plaque index, probing
      depth, and bleeding on probing, was examined. Multiple logistic regression
      analysis was performed to explore risk factors that were associated with
      periodontitis after adjusting for confounding factors. RESULTS: Dental and
      smoking behaviors, dental knowledge, and nutritional status were all
      significantly related to periodontitis. The multiple logistic regression analysis
      showed that patients who had risk factors significantly associated with
      periodontitis were those who had dental scaling during the past year (odds ratio
      [OR]: 2.2), current smokers (OR: 2.47), who received instructions on oral hygiene
      (OR=1.73), and those who were overweight/obese (OR: 4.78). CONCLUSION:
      Periodontitis was correlated with dental and smoking behaviors, dental knowledge,
      and nutritional status in Vietnamese dental patients. Promoting a healthy
      lifestyle, reducing tobacco consumption, motivating oral self-care behaviors,
      together with normal weight maintenance, are necessary to reduce periodontal
      disease burdens.

PMID- 28497902
TI  - Size, Shape, and Lateral Correlation of Highly Uniform, Mesoscopic, Self
      Assembled Domains of Fluorocarbon-Hydrocarbon Diblocks at the Air/Water
      Interface: A GISAXS Study.
AB  - The shape and size of self-assembled mesoscopic surface domains of fluorocarbon
      hydrocarbon (FnHm) diblocks and the lateral correlation between these domains
      were quantitatively determined from grazing incidence small-angle X-ray
      scattering (GISAXS). The full calculation of structure and form factors unravels
      the influence of fluorocarbon and hydrocarbon block lengths on the diameter and
      height of the domains, and provides the inter-domain correlation length. The
      diameter of the domains, as determined from the form factor analysis, exhibits a
      monotonic increase in response to the systematic lengthening of each block, which
      can be attributed to the increase in van der Waals attraction between molecules.
      The pair correlation function in real space calculated from the structure factor
      implies that the inter-domain correlation can reach a distance that is over 25
      times larger than the domain's size. The full calculation of the GISAXS signals
      introduced here opens a potential towards the hierarchical design of mesoscale
      domains of self-assembled small organic molecules, covering several orders of
      magnitude in space.

PMID- 28497903
TI  - Semiconducting Nanowire-Based Optoelectronic Fibers.
AB  - The recent ability to integrate semiconductor-based optoelectronic
      functionalities within thin fibers is opening intriguing opportunities for
      flexible electronics and advanced textiles. The scalable integration of high
      quality semiconducting devices within functional fibers however remains a
      challenge. It is difficult with current strategies to combine high light
      absorption, good microstructure and efficient electrical contact. The growth of
      semiconducting nanowires is a great tool to control crystal orientation and
      ensure a combination of light absorption and charge extraction for efficient
      photodetection. Thus far, however, leveraging the attributes of nanowires has
      remained seemingly incompatible with fiber materials, geometry, and processing
      approaches. Here, the integration of semiconducting nanowire-based devices at the
      tip and along the length of polymer fibers is demonstrated for the first time.
      The scalable thermal drawing process is combined with a simple sonochemical
      treatment to grow nanowires out of electrically addressed amorphous selenium
      domains. First principles density-functional theory calculations show that this
      approach enables to tailor the surface energy of crystal facets and favors
      nanowire growth along a preferred orientation, resulting in fiber-integrated
      devices of unprecedented performance. This novel platform is exploited to
      demonstrate an all-fiber-integrated fluorescence imaging system, highlighting
      novel opportunities in sensing, advanced optical probes, and smart textiles.

PMID- 28497905
TI  - Flavanones: Citrus phytochemical with health-promoting properties.
AB  - Citrus fruit and juices represent one of the main sources of compounds with a
      high potential for health promoting properties. Among these compounds, flavanones
      (such as hesperetin, naringenin, eriodictyol, isosakuranetin, and their
      respective glycosides), which occur in quantities ranging from ~180 to 740 mg/L
      (depending on the Citrus species and cultivar) are responsible for many
      biological activities. These compounds support and enhance the body's defenses
      against oxidative stress and help the organism in the prevention of
      cardiovascular diseases, atherosclerosis, and cancer. Moreover, among other
      properties, they also show anti-inflammatory, antiviral, and antimicrobial
      activities. This review analyzes the biochemistry, pharmacology, and biology of
      Citrus flavanones, emphasizing the occurrence in Citrus fruits and juices and
      their bioavailability, structure-function correlations and ability to modulate
      signal cascades both in vitro and in vivo. (c) 2017 BioFactors, 43(4):495-506,
      2017.

PMID- 28497906
TI  - Cytokine profiling analysis following a non-ablative fractional laser on rat
      skin.

PMID- 28497907
TI  - Effect of TiO2 nanoparticles on some photophysical characteristics of ketocyanine
      dyes.
AB  - The effect of titanium dioxide (TiO2 ) nanoparticles (NPs) on photophysical
      characteristics of 2,5-di[(E)-1-(4-dimethylaminophenyl) methylidine]-1
      cyclopentanone (2,5-DMAPMC) and 2,5-di[(E)-1-(4-diethylaminophenyl)methylidine]-1
      cyclopentanone (2,5-DEAPMC) ketocyanine dyes has been studied using absorption,
      steady-state and time-resolved fluorescence spectroscopy. The magnitudes of
      association constants determined based on modified absorption spectrum of dyes
      due to the presence of TiO2 NPs indicate the interaction of TiO2 NPs with dye
      molecules. The quenching of fluorescence intensity of dyes by TiO2 NPs is
      observed and it follows linear Stern-Volmer (S-V) equation. The magnitude of
      quenching rate parameter suggests the involvement of static quenching mechanism.
      The involvement of electron transfer process in reducing fluorescence intensity
      of dyes has been discussed. Also, varying influence of TiO2 NPs on two dyes is
      explained based on the presence of different alkyl substituent in two dyes.

PMID- 28497908
TI  - The molybdenum cofactor enzyme mARC: Moonlighting or promiscuous enzyme?
AB  - Molybdenum (Mo) is present in the active center of eukaryotic enzymes as a
      tricyclic pyranopterin chelate compound forming the Mo Cofactor (Moco). Four Moco
      containing enzymes are known in eukaryotes, nitrate reductase (NR), sulfite
      oxidase (SO), xanthine oxidoreductase (XOR), and aldehyde oxidase (AO). A fifth
      Moco enzyme has been recently identified. Because of the ability of this enzyme
      to convert by reduction several amidoximes prodrugs into their active amino
      forms, it was named mARC (mitochondrial Amidoxime Reducing Component). This
      enzyme is also able to catalyze the reduction of a broad range of N-hydroxylated
      compounds (NHC) as the base analogue 6-hydroxylaminopurine (HAP), as well as
      nitrite to nitric oxide (NO). All the mARC proteins need reducing power that is
      supplied by other proteins. The human and plants mARC proteins require a
      Cytochrome b5 (Cytb5) and a Cytochrome b5 reductase (Cytb5-R) to form an electron
      transfer chain from NADH to the NHC. Recently, plant mARC proteins were shown to
      be implicated in the reduction of nitrite to NO, and it was proposed that the
      electrons required for the reaction were supplied by NR instead of Cytochrome b5
      components. This newly characterized mARC activity was termed NO Forming Nitrite
      Reductase (NOFNiR). Moonlighting proteins form a special class of multifunctional
      enzymes that can perform more than one function; if the extra function is not
      physiologically relevant, they are called promiscuous enzymes. In this review, we
      summarize the current knowledge on the mARC protein, and we propose that mARC is
      a new moonlighting enzyme. (c) 2017 BioFactors, 43(4):486-494, 2017.

PMID- 28497909
TI  - The therapeutic alliance in different mental disorders: A comparison of patients
      with depression, somatoform, and eating disorders.
AB  - OBJECTIVE: The therapeutic alliance is intensively investigated in psychotherapy
      research. However, there is scarce research on the role of the specific diagnosis
      of the patient in the formation of the therapeutic alliance. Hence, the aim of
      this study was to address this research gap by comparing the alliance in
      different mental disorders. DESIGN: Our sample comprised 348 patients (mean age =
      40 years; 68% female; 133 patients with depression, 122 patients with somatoform
      disorders, and 93 patients with eating disorders). METHODS: Patients completed
      the Working Alliance Inventory and measures of therapeutic outcome in early,
      middle, and late stages of inpatient psychotherapy. We applied multivariate
      multilevel models to address the nested data structure. RESULTS: All three
      disorder groups experienced positive alliances that increased across the course
      of therapy and showed similar alliance-outcome relations that were of comparable
      strengths as in current meta-analyses. However, we found perspective incongruence
      of alliance ratings from patient and therapist in the three disorder groups.
      CONCLUSIONS: Our results generally indicate that the working alliance is of
      importance irrespective of the specific mental disorder. Perspective incongruence
      feedback of working alliance experiences could help to strengthen coordination
      between patient and therapist and thereby improve the therapeutic process.
      Further implications of these findings are discussed. PRACTITIONER POINTS: We
      found no differences in the strengths of alliance ratings and alliance-outcome
      associations in depressive, somatoform, and eating disorder patients. This
      indicates that the working alliance is of general clinical importance
      irrespective of the disorder group and should be a central target in all
      therapies. We found perspective incongruence in alliance ratings between patient
      and therapist in all three disorder groups. Perspective incongruence feedback of
      working alliance experiences could help to strengthen coordination between
      patient and therapist and thereby improve the therapeutic process.

PMID- 28497911
TI  - The Clinical Efficacy of Pollen Extract and Vitamins on Chronic
      Prostatitis/Chronic Pelvic Pain Syndrome Is Linked to a Decrease in the Pro
      Inflammatory Cytokine Interleukin-8.
AB  - PURPOSE: We aim to evaluate the efficacy of pollen extract in association with
      vitamins in patients affected by chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS) and to evaluate the level of the pro-inflammatory mediators interleukin
      (IL)-6, IL-8, and IL-10. MATERIALS AND METHODS: Patients diagnosed with CP/CPPS
      between January and December 2015 were enrolled in this study. Participants were
      randomly assigned to receive oral capsules of pollen extract and vitamins (group
      A) or bromelain (group B) for 3 months. At the enrolment time and 3 months after
      enrolment, all patients completed questionnaires (the National Institutes of
      Health Chronic Prostatitis Symptom Index [NIH-CPSI] and the Short Form-36 and
      underwent urological examinations and microbiological evaluation. Levels of IL-6,
      IL-8, and IL-10 were evaluated in seminal plasma. RESULTS: Sixty-five male
      patients (mean age of 32.7+/-4.7 years) were analysed (group A, n=32; group B,
      n=33). At the follow-up examination, 24 of the 32 patients in group A showed a
      significant reduction in the NIH-CPSI total score compared with 8 of the 33
      patients in the bromelain group (p<0.001). Moreover, the mean level of IL-8 was
      significantly lower in the pollen extract and vitamins group when compared with
      the bromelain group (298 pg/mL vs. 736 pg/mL, respectively; p<0.001). In group A
      we found a statistically significant reduction in the levels of IL-8 between
      enrolment and the follow-up visit (878 pg/mL vs. 298 pg/mL, respectively;
      p<0.001). CONCLUSIONS: Treatment with pollen extract and vitamins improved the
      quality of life in CP/CPPS patients by reducing the levels of pro-inflammatory IL
      8.

PMID- 28497912
TI  - Testosterone Replacement Therapy: Long-Term Safety and Efficacy.
AB  - Recent position statements and guidelines have raised the distinction between a
      true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH).
      The former is the consequence of congenital or acquired "organic" damage of the
      brain centers or of the testis. The latter is mainly secondary to age-related
      comorbidities and does not require testosterone (T) therapy (TTh). In addition,
      concerns related to cardiovascular (CV) safety have further increased the
      scepticism related to TTh. In this paper, we reviewed the available evidence
      supporting the efficacy of TTh in non-organic HG and its long term safety. A
      large amount of evidence has documented that sexual symptoms are the most
      specific correlates of T deficiency. TTh is able to improve all aspects of sexual
      function independent of the pathogenetic origin of the disease supporting the
      scientific demonstration that LOH does exist according to an "ex-juvantibus"
      criterion. Although the presence of metabolic derangements could mitigate the
      efficacy of TTh on erectile dysfunction, the positive effect of TTh on body
      composition and insulin sensitivity might counterbalance the lower efficacy. CV
      safety concerns related to TTh are essentially based on a limited number of
      observational and randomized controlled trials which present important
      methodological flaws. When HG is properly diagnosed and TTh correctly performed
      no CV and prostate risk have been documented.

PMID- 28497914
TI  - Role of Breast-feeding in the Development of Atopic Dermatitis in Early
      Childhood.

PMID- 28497913
TI  - Role of Antioxidants in Assisted Reproductive Techniques.
AB  - Oxidative stress (OS) has been recognized as a significant cause of suboptimal
      assisted reproductive outcome. Many of the sperm preparation and manipulation
      procedures that are necessary in the in vitro environment can result in excessive
      production of reactive oxygen species (ROS) thereby exposing the gametes and
      growing embryos to significant oxidative damage. Antioxidants have long been
      utilized in the management of male subfertility as they can counterbalance the
      elevated levels of ROS inducing a high state of OS. Few studies have looked into
      the clinical effectiveness of antioxidants in patients undergoing assisted
      reproduction. While an overall favorable outcome has been perceived, the specific
      clinical indication and optimal antioxidant regimen remain unknown. The goal of
      our review is to explore the sources of ROS in the in vitro environment and
      provide a clinical scenario-based approach to identify the circumstances where
      antioxidant supplementation is most beneficial to enhance the outcome of assisted
      reproduction.

PMID- 28497915
TI  - In Vitro Diagnostic Testing for Antibiotic Allergy.
AB  - Allergy to antibiotics is an important worldwide problem, with an estimated
      prevalence of up to 10% of the population. Reaction patterns for different
      antibiotics have changed in accordance with consumption trends. Most of the
      allergic reactions to antibiotics have been reported for betalactams, followed by
      quinolones and macrolides and, to a lesser extent, to others, such as
      metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a
      detailed clinical history, which is not always possible and can be unreliable.
      This is usually followed by in vivo, skin, and drug provocation tests. These are
      not recommended for severe, potentially lifethreaten reactions or for drugs that
      are known to produce a high rate of false positive results. Given the limitations
      of in vivo tests, in vitro test can be helpful for diagnosis, despite having
      suboptimal sensitivity. The most highly employed techniques for diagnosing
      immediate reactions to antibiotics are immunoassays and basophil activation
      tests, while lymphocyte transformation tests are more commonly used to diagnose
      non-immediate reactions. In this review, we describe different in vitro
      techniques employed to diagnose antibiotic allergy.

PMID- 28497917
TI  - Does Breast-feeding Relate to Development of Atopic Dermatitis in Young Korean
      Children?: Based on the Fourth and Fifth Korea National Health and Nutrition
      Examination Survey 2007-2012.
AB  - PURPOSE: There have been conflicting reports concerning the relationship between
      breast-feeding and the development of atopic dermatitis (AD) in early childhood.
      The objective of this study was to investigate the associations between breast
      feeding and the risk of AD in early childhood in Korea. METHODS: We combined the
      fourth and fifth Korea National Health and Nutrition Examination Survey data
      collected from 2007 to 2012 and analyzed 2,015 children at 1 to 3 years old.
      Regression analysis was used to determine the association of the following
      variables: AD, feeding types, duration of breast-feeding, and others. RESULTS:
      The annual prevalence of exclusive breast-feeding and AD decreased. Parents with
      allergic diseases preferred breast-feeding and extended duration of feeding
      compared with those without. In multiple logistic regression analyses, exclusive
      breast-feeding in feeding type I (P=0.070; adjusted odds ratio [OR]=1.990),
      exclusive breast-feeding in feeding type II (P=0.095; adjusted OR=1.495) and
      breast-feeding duration (P=0.430; adjusted OR=1.013) were not significantly
      related to AD. CONCLUSIONS: Breast-feeding was not found to be associated with an
      occurrence of AD in young children. Rather, parents with histories of allergic
      diseases tended to prefer breast-feeding and extend its duration. To clarify the
      role of breast-feeding in the development of AD, a nation-wide prospective study
      is needed.

PMID- 28497916
TI  - Emerging Endotypes of Chronic Rhinosinusitis and Its Application to Precision
      Medicine.
AB  - Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various
      underlying pathophysiologic mechanisms which translate to endotypes, in contrast
      to clinical phenotypes or histological subtypes. Defining endotypes can help
      clinicians predict disease prognosis, select subjects suitable for a specific
      therapy, and assess risks for comorbid conditions, including asthma. Therefore,
      with recent advancement of biologicals in CRS clinical trials, endotyping can be
      a breakthrough in treating recalcitrant CRS. CRS is caused by dysregulated
      immunologic responses to external stimuli, which induce various inflammatory
      mediators from inflammatory cells, including innate lymphoid cells (ILCs) and T
      lymphocytes as well as epithelial cells. Thymic stromal lymphopoietin (TSLP),
      interleukin (IL)-25, and IL-33, which are mainly secreted by epithelial cells in
      response to external stimuli, act on type 2 ILCs and T helper 2 (Th2) cells,
      inducing IL-4, IL-5, and IL-13. Local immunoglobulin E (IgE) production is also a
      signature event in nasal polyps (NP). These inflammatory mediators are novel
      potential therapeutic targets for recalcitrant CRS. This article reviews recent
      publications regarding endotypes and endotype-based therapeutic strategies in CRS
      and NP.

PMID- 28497919
TI  - Accurate Determination of Childhood Food Allergy Prevalence and Correction of
      Unnecessary Avoidance.
AB  - PURPOSE: Because the true prevalence of food allergy (FA), as based on the
      results of an oral food challenge test (OFC), is unknown, it is likely that
      children with suspected FA unnecessarily eliminate potentially causative foods.
      This study aimed to identify the prevalence of FA and to determine the proportion
      of children who unnecessarily eliminate food. METHODS: To identify children with
      FA, a primary survey was conducted via a questionnaire with all children aged 0
      18 years in Niijima village (remote islands of Japan). In the secondary survey, a
      detailed medical interview was conducted by doctors with children who currently
      did not eat some foods. The third survey involved serum food-specific
      immunoglobulin E (IgE) tests and an OFC for children with suspected FA. RESULTS:
      Of 376 enrolled children, 374 (99.5%) completed the questionnaire. Some foods
      were eliminated by 18.6% and 13.0% of all children and those >=6 years old,
      respectively. The target population for the secondary survey included 69 children
      who all completed the medical interview. The target population for the third
      survey consisted of 35 children, of whom 26 (74.3%) underwent the blood test. An
      OFC was performed 35 times with 20 children. As a result, the prevalence of FA
      was 4.9% in children of all ages and 4.7% in those >=6 years old. Moreover, 55.0%
      children were able to cease eliminating food intake. CONCLUSIONS: It is possible
      that a considerable number of children unnecessarily eliminate food because of
      suspected FA.

PMID- 28497918
TI  - Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO.
AB  - PURPOSE: The nature of allergic rhinitis (AR) in preschool aged children remains
      incompletely characterized. This study aimed to investigate the prevalence of AR
      and its associated risk factors in preschool-aged children and to assess the
      clinical utility of fractional exhaled nitric oxide (FeNO). METHODS: This general
      population-based, cross-sectional survey included 933 preschool-aged (3- to 7
      year-old) children from Korea. Current AR was defined as having nasal symptoms
      within the last 12 months and physician-diagnosed AR. RESULTS: The prevalence of
      current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted
      odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of
      antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an
      increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI,
      0.35-0.75) reduced the risk. Children with current atopic AR had significantly
      higher geometric mean levels of FeNO compared to those with non-atopic rhinitis
      (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62
      12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38,
      P<0.001). The FeNO levels were higher in children with current atopic AR compared
      with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083).
      CONCLUSIONS: Mold exposure and use of antibiotics during infancy increases the
      risk of current AR, whereas having an older sibling reduces it. Children with
      current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis
      cases, suggesting that FeNO levels may be a useful discriminatory marker for
      subtypes of AR in preschool children.

PMID- 28497920
TI  - Prevalence of Self-reported Allergic Diseases and IgE Levels: A 2010 KNHANES
      Analysis.
AB  - PURPOSE: The prevalence of allergic diseases is known to be associated with both
      demographic and environmental factors. Herein, we aimed to determine significant
      factors associated with the prevalence of allergic diseases and with total
      immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea.
      METHODS: We analyzed unweighted data collected by the 2010 Korea National Health
      and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for
      tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica,
      representing a sample of 16,003,645 citizens, by considering the sample weight
      and stratification. RESULTS: The overall prevalence of self-reported allergic
      diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic
      dermatitis decreased with age, whereas the asthma prevalence was not affected by
      the age of the subjects. When analyzed according to the type of allergic
      diseases, the prevalence of self-reported allergic disease was significantly
      associated with various factors (e.g. age, occupation, living in urban areas, and
      depression). The tIgE level decreased with age, but later increased. Elevation of
      tIgE was significantly associated with male sex, type of occupation, obesity, and
      smoking status. However, the risk factors for the increased sIgE levels to each
      allergen were quite different. Sensitization to D. farinae was more likely in
      young subjects, whereas the prevalence of sensitization to B. germanica was
      significantly higher in subjects with male sex, residing in a house (houses), and
      with glucose intolerance. Finally, young age and the smoking status were
      significantly associated with sensitization to dog. CONCLUSIONS: Various
      demographic and environmental factors were significantly associated with the
      prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to
      D. farinae, B. germanica, and dog in Korea.

PMID- 28497921
TI  - Macrolide Resistance and Its Impacts on M. Pneumoniae Pneumonia in Children:
      Comparison of Two Recent Epidemics in Korea.
AB  - PURPOSE: The aim of this study was to investigate the change in macrolide
      resistance rate in pediatric Mycoplasma pneumoniae pneumonia and to evaluate the
      influence of macrolide-resistant M. pneumoniae (MRMP) on the clinical course of
      disease, by comparing 2 recent, consecutive epidemics in Korea. METHODS: A total
      of 250 patients with M. pneumoniae pneumonia admitted to a single tertiary
      hospital were enrolled in this study. Detection of MRMP was based on specific
      point mutations in domain V of the 23S rRNA gene. The medical records of enrolled
      patients were reviewed retrospectively, and the clinical courses and laboratory
      data were compared. RESULTS: The macrolide resistance rate of M. pneumoniae was
      51.1% (48/94) in the 2011 epidemic, and 87.2% (136/156) in the 2015 epidemic. All
      MRMP isolates had the A2063G point mutation. In comparison of 2 epidemics, the
      mean age of patients with M. pneumoniae pneumonia was increased, and the total
      febrile days and febrile days after initiation of macrolides were prolonged in
      the 2015 epidemic. Overall severity of MRMP or macrolide-susceptible M.
      pneumoniae (MSMP) pneumonia over 2 epidemics was not significantly changed.
      However, the proportion of patients who had a fever lasting more than 72 hours
      after initiation of macrolides and who received corticosteroid treatment were
      higher in MRMP pneumonia during 2 epidemics. CONCLUSIONS: The macrolide
      resistance rate of M. pneumoniae has risen rapidly over 2 recent, consecutive
      epidemics, and this has been associated with a prolonged clinical course and
      increased use of corticosteroids to treat pediatric M. pneumoniae pneumonia.

PMID- 28497922
TI  - Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of
      Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross
      Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin.
AB  - PURPOSE: Reports evaluating diagnosis and cross reactivity of quinolone
      hypersensitivity have revealed contradictory results. Furthermore, there are no
      reports investigating the cross-reactivity between gemifloxacin (GFX) and the
      others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity
      reactions to quinolones and to evaluate the cross reactivity between different
      quinolones including the latest quinolone GFX. METHODS: We studied 54 patients
      (mean age 42.31+/-10.39 years; 47 female) with 57 hypersensitivity reactions due
      to different quinolones and 10 nonatopic quinolone tolerable control subjects. A
      detailed clinical history, skin test (ST), and single-blind placebo-controlled
      drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and
      lymphocyte transformation test (LTT) were performed with the culprit and
      alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX),
      levofloxacin (LFX), ofloxacin (OFX), and GFX. RESULTS: The majority (75.9%) of
      the patients reported immediate type reactions to various quinolones. The most
      common culprit drug was CFX (52.6%) and the most common reaction type was
      urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs,
      although their STs were negative; while false ST positivity was 3.5% and
      ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in
      quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX
      and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX
      hypersensitive patients the degree of cross-reactivity to the other quinolones
      was 16.7%. CONCLUSIONS: These results suggest that STs, BAT, and LTT are not
      supportive in the diagnosis of a hypersensitivity reaction to quinolone as well
      as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are
      necessary to identify both culprit and alternative quinolones.

PMID- 28497923
TI  - CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in
      a Mouse Model of Eosinophilic Gastroenteritis.
AB  - PURPOSE: Although the role of eosinophils in eosinophilic gastroenteritis (EGE)
      is not fully understood, they are believed to be a principal effector cell.
      Previous studies have demonstrated that eotaxin and its specific receptor,
      cysteine-cysteine chemokine receptor-3 (CCR3), play a central role in eosinophil
      trafficking into the gastrointestinal (GI) tract. Thus, we examined the targeting
      of CCR3 as a potential therapeutic intervention for EGE in a mouse model.
      METHODS: Eight- to 10-week-old BALB/c mice were intraperitoneally sensitized and
      intragastrically challenged with ovalbumin (OVA). Different groups of mice were
      administered either an anti-CCR3 antibody or a control IgG by intraperitoneal
      injection 1 hour before each OVA challenge. Eosinophilic inflammation in the
      intestinal mucosa, mucosal injury, and severity of diarrhea were compared between
      different groups at 1 hour after final OVA challenge. RESULTS: Anti-CCR3 antibody
      reduced the number of eosinophils in peripheral blood and intestinal mucosa, but
      not in bone marrow. This reduction was associated with restoration of reduced
      villous crypt ratio, increased intestinal epithelial cell proliferation, and
      weight loss induced by OVA challenge. However, Anti-CCR3 antibody had no effect
      on the level of OVA specific immunoglobulin E (IgE) and the expression of
      critical chemokines or cytokines in eosinophil trafficking into the GI tract,
      such as eotaxin-1, interleukin (IL)-5, and IL-13. CONCLUSIONS: Anti-CCR3 antibody
      significantly reduced the severity of eosinophilic inflammation, mucosal injury,
      and diarrhea in a mouse model of food allergen-induced GI eosinophilic
      inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and
      other GI eosinophil-mediated diseases.

PMID- 28497924
TI  - Real-life Efficacy of Omalizumab After 9 Years of Follow-up.
AB  - Omalizumab is frequently used as add-on treatment to inhaled corticosteroids
      (ICS) and long-acting beta2-agonists in patients with suboptimal control of
      severe asthma. Patients with severe asthma will typically require chronic
      treatment, although due to the limited amount of data available there are still
      some concerns about the safety and efficacy of long-term therapy with omalizumab.
      Herein, in an extension of a previous 4-year study, we report disease-related
      outcomes of 8 patients with severe persistent allergic asthma who have been
      followed for a total of 9 years in a real-life setting. Both quality of life
      (QoL) (evaluated using the Juniper Asthma-Related QoL Questionnaire [AQLQ]) and
      forced expiratory volume in 1 second (FEV1) showed sustained improvement at 9
      years. The median values of AQLQ and FEV1 at 4 years were 5.5 and 82.0% compared
      to 5.9 and 85.5%, respectively, at 9 years, which were all significantly
      increased from baseline. After 9 years, the mean annual number of severe
      exacerbations was 0.63 compared to 5 at baseline. There also appeared to be a
      trend toward use of a lower dose of ICS at longer follow-up times. After 9 years,
      there were no safety concerns for continued use of omalizumab, and no asthma
      related hospitalizations or emergency department visits were documented over the
      last 5 years. The present analysis is the longest reported clinical follow-up of
      omalizumab. Long-term maintenance treatment with omalizumab for up to 9 years is
      associated with continued benefits in reducing symptoms, exacerbations, and
      medication burden without any safety concerns.

PMID- 28497925
TI  - Increased Risk of Chronic Spontaneous Urticaria in Patients With Autoimmune
      Thyroid Diseases: A Nationwide, Population-based Study.
AB  - There was no previous population-based study on the comparison of the risk of
      chronic spontaneous urticaria (CSU) between autoimmune thyroid diseases (AITD)
      and age- and gender-matched controls. The primary objective of this study was to
      evaluate the risk of CSU after diagnosis of AITD using national registry data
      from Korea. The secondary objective was to evaluate other risk factors of CSU.
      Based on the disease code diagnoses in 2003-2005, we composed an AITD group
      (n=3,659) and an age- and gender-matched control group (n=18,295). Each patient
      was tracked for whether CSU occurs or not until 2013. After adjusting for
      demographic differences and comorbidities, patients with AITD had a significantly
      higher rate of CSU compared to the control group (hazard ratio [HR], 1.46; 95%
      confidence interval [CI], 1.25-1.70; P<0.001). Among the AITD patients, the
      adjusted HR for CSU was higher in patients with Hashimoto's thyroiditis (HR,
      1.50) than in those with Grave's disease (HR, 1.33), although the difference was
      not statistically significant (P=0.368). Analysis of CSU patients associated with
      AITD showed that female patients had a significantly higher risk of CSU compared
      to male ones (HR, 1.34; P=0.001) and that those with allergic rhinitis (HR, 1.51;
      P<0.001), atopic dermatitis (HR, 2.44; P<0.001), and asthma (HR, 1.50; P<0.001)
      had a significantly higher risk of CSU compared to patients without respective
      diseases. Our results demonstrated that AITD could be significantly associated
      with an increased risk of CSU.

PMID- 28497926
TI  - Plasma LTE4/PGF2alpha Ratio and Blood Eosinophil Count Are Increased in Elderly
      Asthmatics With Previous Asthma Exacerbation.
AB  - The tools for asthma control assessment recommended by the current guideline are
      cognitive function- and effort-dependent, which is substantially impaired in the
      elderly. The aim of this study is to investigate objective assessment tools of
      asthma control status and previous asthma exacerbation (AE) in elderly subjects.
      Asthmatics aged >60 years who were treated with step 2 or 3 by the Global
      Initiative for Asthma (GINA) guideline were enrolled. During the 12-week study
      period, the subjects used either 400 MUg of budesonide plus 10 mg of montelukast
      or 800 MUg of inhaled budesonide. The occurrence of AE during the 4-week run-in
      and 12-week treatment period was monitored. After 12-week of treatment, sputum
      eosinophil count, peripheral eosinophil count, the plasma leukotriene E4 (LTE4),
      and prostaglandin F2alpha (PGF2alpha) metabolite levels were measured using the
      UHPLC/Q-ToF MS system. The study subjects were divided into group 1 (asthmatics
      who experienced AE during the study period) and group 2 (those who did not). A
      total of 101 patients aged 60-85 years were enrolled. Twenty-three patients
      (22.8%) had experienced AE. The plasma LTE4 level, LTE4/PGF2alpha ratio, and
      peripheral eosinophil count were significantly higher in group 1 than in group 2
      (P=0.023, P=0.010, P=0.033, respectively). The plasma LTE4/PGF2alpha ratio and
      peripheral eosinophil count at week 12 were significantly associated with
      previous AE (odds ratio [OR]=1.748, P=0.013; OR=1.256, P=0.027). Receiver
      operating characteristic (ROC) curves to discriminate the subjects with previous
      AE, including these 2 parameters, showed that the area under the curve was 0.700
      (P=0.004), with 73.9% sensitivity and 47.9% specificity. In conclusion, a
      combination of plasma LTE4/PGF2alpha ratio and peripheral eosinophil count can be
      an objective assessment tool which is significantly associated with asthma
      control status in elderly asthmatics.

PMID- 28497927
TI  - The potential role of pain-related SSEPs in the early prognostication of long
      term functional outcome in post-anoxic coma.
AB  - BACKGROUND: Cardiac arrest (CA) is a common cause of disability. Multimodal
      evaluation has improved prognosis but precocious biomarkers are not appropriate
      in determining long-term functional outcome. AIM: To identify early
      prognostication markers of long-term functional outcome in post-anoxic coma.
      DESIGN: Retrospective assessment of outcomes. POPULATION: Individuals older than
      18 years with post-anoxic coma hospitalized in intensive care units after cardiac
      arrest (CA) regardless of cause (cardiac or non-cardiac) and location of event
      (in or out-of-hospital). METHODS: Clinical, biological and neurophysiological
      data were collected within 48 hours from CA. Clinical data included time of no
      and low flow, CA rhythm, pupillary reflex, Glasgow motor score at admission and
      hyperthermia. Biological marker was the highest creatinine level.
      Neurophysiological parameters included EEG pattern and reactivity, Somatosensory
      Evoked Potential (SSEP), and Middle-Latency (ML) SSEP evoked at low (10 mA) and
      high (50 mA) intensity stimulation. Level of Cognitive Functioning Scale (LCFS),
      Disability Rating Scale and recovery from coma (Revised coma Recovery Scale [CRS
      R]) were collected at 12 months. A LASSO multiple regression analysis was fitted
      to data to investigate the best predictors of LCF, DRS and CRS-R. In-sample
      prediction was obtained to verify the quality of fitting, and accuracy indices
      (i.e., total error rate) produced. RESULTS: Presence of short and medium latency
      SSEPs with low and high stimulation intensity were identified as prognostic
      predictors of outcome for all the scales. Error rate was 4.5% for CRS and LCF,
      and 9.1% for DRS. CONCLUSIONS: Middle latency somatosensory evoked potentials
      associated with short latency somatosensory evoked potentials during the first 48
      hours after a cardiac arrest are strong predictors of functional outcome at 12
      months from the event. Replication on larger cohorts is needed to support their
      routine use as prognostic markers. CLINICAL REHABILITATION IMPACT: These markers
      could inform more appropriate allocation of resources, provide a basis for
      realistic goal-setting, and help the family to adjust its expectations.

PMID- 28497928
TI  - Effects of dual- and complex-task on walking ability of ambulatory individuals
      with spinal cord injury.
AB  - BACKGROUND: Attempting to perform dual- and complex-tasks obviously reduces the
      walking ability of individuals with impaired cognitive functions. However, there
      is no clear evidence describing the effects of dual- and complex-tasks on the
      walking ability of ambulatory individuals with a spinal cord injury (SCI) who
      have intact cognitive functions, but suffer from various degrees of sensorimotor
      deterioration. AIM: To primarily investigate the effects of dual- and complex
      task on the walking ability of ambulatory subjects with SCI as compared to
      healthy individuals. In addition, the study secondarily compared the effects in
      subgroups of subjects with SCI, including different age groups, lesion severity
      and level of ability. DESIGN: Cross-sectional design. SETTING: A major tertiary
      referral and community hospitals in Thailand. POPULATION: Thirty-seven ambulatory
      individuals with SCI and 13 healthy subjects. METHODS: All subjects were
      evaluated for outcomes while they walked under four conditions, including single
      task overground walking (ST-OG), dual-task overground walking (DT-OG) using a
      color word Stroop task, single-task obstacle crossing (ST-OC) and dual-task
      obstacle crossing (DT-OC). The outcomes were compared among the conditions and
      between the groups of subjects in terms of walking time, obstacle crossing
      ability and percent of Stroop task errors. RESULTS: With the increasing
      complexity of the tasks, both SCI and healthy subjects walked significantly
      slower (P<0.001 for those with SCI and P<0.05 for healthy subjects), but not when
      compared between the ST-OC and DT-OG conditions (P>0.05). Subjects also showed a
      greater percentage of cognitive task errors when they encountered a dual- and
      complex-task, particularly those with SCI who were over 50 years old, had mild
      lesion severity or walked with a walking device (P<0.001). CONCLUSIONS: The
      incorporation of dual- and complex-task challenged cognitive-motor interference
      of ambulatory individuals with SCI. CLINICAL REHABILITATION IMPACT: The
      application of such tasks may benefit rehabilitation outcomes in a real-world
      situation for patients, especially for those who are older than 50, have mild
      lesion severity or use a walking device.

PMID- 28497929
TI  - Measurement properties of the Swedish modified version of the Postural Assessment
      Scale for Stroke Patients (SwePASS) using Rasch analysis.
AB  - BACKGROUND: A previous small-sample (N.=150) Rasch analysis of the Swedish
      modified version of the Postural Assessment Scale for Stroke Patients (SwePASS)
      suggested problems regarding response categories and redundant items that need
      confirmation in larger samples with more severe strokes. AIM: The aim of this
      study was to evaluate the measurement properties of the SwePASS in patients with
      acute stroke. DESIGN: A multicenter, cross-sectional study. SETTING: Two stroke
      units in Western Sweden. POPULATION: The study cohort included 250 consecutive
      inpatients undergoing rehabilitation after acute stroke. METHODS: The SwePASS
      assessments were performed once within the first four days after admission to the
      stroke units. The data were analyzed according to the Rasch measurement model
      regarding targeting, model fit, reliability, response category function, local
      dependence and differential item functioning. RESULTS: Postural control of 250
      patients (median age, 76.5 years) was assessed with the SwePASS within median of
      two days after admission to the stroke units. The SwePASS covered a continuum of
      different levels of postural control, but had suboptimal targeting with
      insufficient representation of lower and higher levels of postural control. The
      reliability was high, the item fit statistics were generally acceptable and there
      was no differential item functioning by sex, age and stroke localization.
      However, response categories did not function as expected for four of the 12
      SwePASS items and five items exhibited local dependency. CONCLUSIONS: The SwePASS
      exhibited several promising measurement properties. To improve the scale, poor
      targeting, illogical response categories and local dependency should be
      addressed. CLINICAL REHABILITATION IMPACT: The SwePASS provides valuable clinical
      information regarding postural control in the acute phase after stroke.

PMID- 28497930
TI  - Mirror therapy for involuntary movement due to chronic thalamic hemorrhage: a
      case report.
AB  - BACKGROUND: Some stroke survivors suffer from involuntary movement, which often
      disturbs upper-limb function, but there are few effective modality options. CASE
      REPORT: A 70-year-old man presented with persisting right-upper-limb hemiballism
      due to left thalamic hemorrhage ten years before. We provided inpatient
      rehabilitation, including repetitive-facilitative exercise and task-related
      training, and prescribed clonazepam from day 5 after admission. However, the
      affected upper limb showed no significant change and remained nonfunctional. When
      we introduced mirror therapy (MT) to the rehabilitation program on day 14,
      hemiballism immediately decreased during the MT session, so we added daily MT
      sessions of 20 min/day. At discharge on day 42, he was able to use his right hand
      for eating meals and folding laundry. CLINICAL REHABILITATION IMPACT: This shows
      that MT may have the potential to be a novel therapeutic method for treating
      involuntary movement. Further research is needed to elucidate mechanisms by which
      MT may reduce hemiballism.

PMID- 28497931
TI  - Is outpatient continuous regional analgesia more effective and equally safe than
      single-shot peripheral nerve blocks after ambulatory orthopedic surgery?
AB  - INTRODUCTION: Continuous regional analgesia is an established technique for
      effective postoperative pain treatment, particularly after orthopedic surgical
      procedures. Even if it has been increasingly applied to the outpatient setting as
      well, many anesthesiologists are still reluctant to discharge patients with a
      perineural catheter in place. Aim of this review was to clarify the evidences
      about safety and effectiveness of outpatient continuous peripheral nerve blocks.
      EVIDENCE ACQUISITION: A systematic review of all prospective, randomized, double
      blinded, placebo-controlled trials of the last 20 years on outpatient continuous
      peripheral nerve blocks after ambulatory orthopedic surgery was performed, using
      both PubMed and OVID databases were. Study quality was assessed using the
      modified Jadad Scale. Primary outcomes were pain at 24 and 48 hours and morphine
      consumption. EVIDENCE SYNTHESIS: Five studies matched the inclusion criteria and
      were considered of good quality to be included in the review process. All these
      studies consistently showed a better pain control both at rest and during
      movement within the first postoperative day, leading to a reduced opioid
      consumption in patients treated with outpatient continuous regional analgesia.
      However, only three studies showed these advantages to be sustained longer than
      the first 24 hours postoperatively. No severe complications were reported.
      CONCLUSIONS: High-quality evidences about outpatient regional analgesia are
      scarce. Considering the advantages of continuous peripheral nerve blocks in the
      inpatient setting more prospective studies assessing also functional recovery are
      needed to further implement these techniques in the ambulatory setting.

PMID- 28497932
TI  - Individual duration of axillary brachial plexus block is unpredictable: a
      prospective double centered observational study.
AB  - BACKGROUND: The duration of effect for axillary plexus block using ropivacaine is
      highly variable. The available literature does not offer any plausible means of
      predicting time of block offset for individual patients, making it difficult to
      give accurate information and plan postoperative analgesics. This study was
      designed to identify factors influencing axillary plexus block offset time.
      METHODS: A total of 92 patients participated in this prospective double centred
      observational study. All patients were scheduled for axillary plexus block with
      ropivacaine 0.75% and subsequent block duration was recorded. RESULTS: Mean time
      of axillary plexus block offset was 13.5 hours, with a range of 4.8 to 25.4
      hours. No statistical significant differences in offset time was seen with regard
      to gender, age, body weight, BMI and ASA-classification. A trend for increasing
      duration of blocks associated with increasing age was observed. No statistically
      significant difference was identified in block duration between blocks performed
      with nerve stimulator guidance versus ultrasound guidance. Similarly, neither
      dose nor volume of ropivacaine 0.75% was identified as a factor influencing block
      duration. CONCLUSIONS: This prospective study demonstrates a large inter
      individual variation in time of axillary plexus block offset using ropivacaine
      0.75%. The lack of association between offset time and both demographic and block
      performance factors, makes predictability of individual duration of axillary
      plexus blocks in clinical practice extremely difficult. We suggest that all
      patients should be made aware of such variability in duration prior to block
      placement.

PMID- 28497933
TI  - Scalp block for glioblastoma surgery is associated with lower inflammatory scores
      and improved survival.
AB  - BACKGROUND: Regional anesthesia has anti-inflammatory effects. Recent studies
      suggest that regional anesthesia might improve the survival of patients with
      cancer. We hypothesized that the use of a scalp block (SB) during craniotomy for
      glioblastoma (GB) decreases the postoperative systemic and local inflammatory
      response and extend their survival. METHODS: This retrospective study included
      119 patients with GB who underwent tumor resection. We divided patients into 2
      groups based on the use of SB during surgery. Preoperative and postoperative
      neutrophil-to-lymphocyte (NLR) ratio and platelet-to-lymphocyte (PLR) ratios were
      calculated as well as the percentage change in postoperative T2/FLAIR (FLuid
      Attenuated Inversion Recovery) volume. Both markers of the inflammatory response
      were compared between patients with and without an SB. Progression-free survival
      (PFS) was also compared in both groups of patients. Univariate and multivariate
      analysis were used to test the association between SB and patients' survival.
      RESULTS: On day 3 after surgery, patients who had an SB showed statistically
      significant lower NLRs and PLRs than those without an SB. There was also a
      significant larger reduction in postoperative T2/FLAIR signal in patients with SB
      than in those without SB. The median PFS (progression-free survival) was longer
      in patients with SB (16.7 months) than those without an SB (6.5 months, P<0.001).
      The multivariate analysis indicated that the use of SB was an independent factor
      for longer PFS (hazard ratio: 0.31 95% confidence interval: 0.07-0.21, P<0.001).
      CONCLUSIONS: This retrospective study supports the hypothesis that in patients
      with GB undergoing craniotomy, the use of SB is associated with lower levels of
      systemic and local inflammation, and longer survival.

PMID- 28497934
TI  - Cerebral autoregulation monitoring in acute traumatic brain injury: what's the
      evidence?
AB  - Cerebral autoregulation is conceptualized as a vascular self-regulatory mechanism
      within the brain. Controlled by elusive relationships between various biophysical
      processes, it functions to protect the brain against potential damages caused by
      sudden changes in cerebral perfusion pressures and flow. Following events such as
      traumatic brain injuries (TBI), autoregulation may be compromised, potentially
      leading to an unfavorable outcome. In spite of its complexity, autoregulation has
      been able to be quantified non-invasively within the neuro-critical care setting
      with the aid of transcranial Doppler. This information is interpreted
      particularly through calculated derived indices based on commonly-monitored input
      signals such as arterial blood pressure and intracranial pressure (i.e. Pressure
      Reactivity Index [PRx], Mean Flow Index, etc.). For example, PRx values that
      trend towards positive numbers are correlated with unfavorable outcome. These
      predictors are primarily surrogate markers of cerebral hemodynamic activity,
      although suggesting robust correlations between these indices and patient
      outcome. This review of the literature seeks to explain the methodology behind
      the calculations of various measures of autoregulation in adult patients
      suffering from traumatic brain injuries, and how they can interact with one
      another to both create larger effects on patient outcome and general outcome
      prediction models. Insight into the driving forces behind cerebral autoregulation
      is imperative for guiding both clinical decision-making and global treatment
      protocols for neuro-critically ill patients. The evidence that autoregulation
      oriented therapy may improve outcome after TBI is still oscillating around Level
      III.

PMID- 28497935
TI  - The LMA-Flexible: time to celebrate a unique extraglottic airway device.

PMID- 28497936
TI  - Grading health claims by weight of evidence would make for a better-informed
      public.
AB  - In the European Regulation 1924/2006 and especially its first recital, the
      evaluation of health claims (HC) by European Food Safety Agency (EFSA) was
      introduced so as "to ensure a high level of consumer protection, [and] give the
      consumer the necessary information to make choices in full knowledge of the
      facts...". Now, with 10 years of hindsight since the Regulation was adopted, it
      can be asked whether EFSA HC process of evaluation that led to a marginal number
      of accepted claims is consistent with this objective, not just for protecting
      consumers but for allowing them to decide freely and make informed choices. The
      aim of this paper was to demonstrate that the inclusion of a ranking of the
      weight of evidence in the assessment of EFSA's scientific substantiation of HC
      would allow consumers to benefit from the very high standard of scientific
      evaluation performed by EFSA. The definition of standards of proof is a
      generalized practice and rests on the principle that evaluations of health
      practices should be understood in terms of descriptions ranging from formal proof
      from high-power double-blind placebo-controlled studies to rankings based on the
      consensus views of experts or even agreement among professionals. Grading of
      weight of evidence - not of scientific expertise - is pervasive in all the
      recommendations or consensus meetings of health authorities or learned societies.
      This approach would stimulate research and product innovation as industrials
      would see a positive return on investment.

PMID- 28497937
TI  - Cone-beam volumetric imaging in craniofacial medicine.
AB  - With the development of x-ray computed tomography (CT) in the 1960s and its first
      use for clinical studies in 1972 by Sir Godfrey Hounsfield, radiological
      tomography attained widespread use and today is one of the essential imaging
      techniques in medical radiology. It is a technically mature and clinically widely
      accepted method and complements classical x-ray panoramic radiography in many
      areas. The technology is frequently used in craniofacial radiology, because of
      its characteristic low radiation dose, high spatial resolution and lower cost
      compared with CT. The aim of this work is to: describe the principles of Cone
      beam computed tomography (CBCT), to make a brief description of the existing
      devices, to present briefly the use of 3D diagnosis in craniofacial medicine.

PMID- 28497938
TI  - Cardiovascular consequences of hypophosphatemia.
AB  - INTRODUCTION: Few studies have been conducted to evaluate the effect of
      hypophosphatemia on cardiovascular consequences. The goal of this review was to
      determine whether hypophosphatemia is associated with cardiovascular consequences
      and to increase its awareness as a new clinical entity and a reversible cause of
      cardiovascular consequences. EVIDENCE ACQUISITION: We searched MEDLINE and PubMed
      through September 2016 for primary studies that reported the relationship between
      hypophosphatemia and cardiovascular consequences including cardiomyopathy and
      arrhythmia. EVIDENCE SYNTHESIS: A total of 937 articles were initially obtained.
      Of these articles, 921 publications were excluded according to the inclusion and
      exclusion criteria. Sixteen articles were included in this review. These articles
      included 3 prospective cohort studies, 1 retrospective cohort study, 7 case
      series or case reports, 2 case-control studies, 1 pre- vs. post-test in a single
      group, and 2 animal studies. CONCLUSIONS: The mechanisms of hypophosphatemia in
      cardiomyopathy and arrhythmia have been reported to be a depletion of adenosine
      triphosphate in myocardial cells and decreased 2,3-diphosphoglycerate in
      erythrocytes. Left ventricular performance seems to improve when severe
      hypophosphatemia is corrected, but not in those with mild to moderate
      hypophosphatemia. However, analyses of the relationship between cardiac function
      and hypophosphatemia using clinical end points have not been conducted. The
      association between hypophosphatemia and arrhythmia remains unclear, but
      anecdotal reports exist in the literature.

PMID- 28497939
TI  - Role for imaging in spondyloarthritis.
AB  - INTRODUCTION: Despite major progress in the imaging diagnosis of
      spondyloarthritis (SpA), the relative advantages of various available imaging
      techniques remain unclear. The aim of this study is to assess the current use of
      imaging in the diagnosis of SpA and to provide suitable recommendations for the
      use of imaging as an outcome measure as defined in the Assessment in
      SpondyloArthritis international Society (ASAS) criteria. EVIDENCE ACQUISITION: A
      systematic literature search regarding imaging in SpA was performed. Articles
      were assessed by two reviewers to identify and summarized key information
      pertaining to imaging in SpA. EVIDENCE SYNTHESIS: The search identified 180
      relevant articles. Conventional radiography (CR) (17 articles), ultrasound (US)
      (26 articles), conventional computed tomography (CT) (13 articles), spectral
      computed tomography (spectral CT) (2 articles), bone scintigraphy (24 articles),
      and magnetic resonance imaging (MRI) were assessed (98 articles). Sacroiliitis
      and enthesitis were the major imaging findings in SpA. Multiple studies assessed
      the feasibility, validity, or differences among imaging modalities for the
      diagnosis of SpA; however, comprehensive assessments were not available due to a
      paucity of prospective imaging studies. CR is a widely available, inexpensive
      initial approach to evaluate patients with suspected SpA. CT enables assessment
      of structural changes from chronic sacroiliitis including bony erosions,
      subchondral sclerosis, joint space narrowing, and ankyloses; however, both CR and
      CT modalities are insensitive for demonstrating early enthesitis and sacroiliitis
      in SpA. US mainly identifies appendicular enthesitis but is more limited with
      respect to the sacroiliac joints. Bone scintigraphy can identify sacroiliac joint
      lesions and semi-quantitatively assess active sacroiliitis. MRI optimally
      evaluates not only early enthesitis and sacroiliitis of SpA but also chronic
      structural changes to the sacroiliac joints. CONCLUSIONS: More than one modality
      may be required for diagnostic and assessment of SpA depending upon disease
      characteristics and evolution. CR is a suitable initial examination while MRI is
      able to detect both early and late changes of SpA. A combination of CR and MRI is
      recommended for the diagnosis and assessment of SpA.

PMID- 28497940
TI  - Evaluation of diabetic foot infection in nuclear medicine.
AB  - Diabetic foot infection is not only the most common cause of hospitalization
      among diabetic patients, but is also associated with high morbidity, mortality
      and major utilization of the resources. Managing diabetic patients with suspected
      foot infection is highly dependent on an early and accurate determination of its
      presence and location. Medical imaging is often used in the workup of these
      patients, as clinical diagnosis of osteomyelitis is often difficult, and invasive
      bone biopsy is infrequently used due to many limitations. In this article, we
      review the role and accuracy of commonly used medical imaging modalities in the
      evaluation of diabetic patients with suspected foot infection including
      osteomyelitis with particular emphasis on molecular nuclear medicine imaging. The
      impact of imaging on patients' management is also discussed. We finally comment
      on possible future directions in hybrid molecular imaging techniques.

PMID- 28497941
TI  - Antiarrhythmic effects of ranolazine used both alone for prevention of atrial
      fibrillation and as an add-on to intravenous amiodarone for its pharmacological
      cardioversion: a meta-analysis.
AB  - INTRODUCTION: Recent evidence from relatively small randomized controlled trials
      would seem to support a useful role of ranolazine for the prevention and
      treatment of atrial fibrillation (AF). The present study is aimed at providing
      information about the possible beneficial anti-arrhythmic properties of
      ranolazine. In particular, the meta-analysis carried out in this study focuses on
      the application of ranolazine to prophylaxis and treatment of atrial
      fibrillation. EVIDENCE ACQUISITION: Both methods randomized controlled trials
      (RCTs) and non-randomized observational studies concerning the effects of
      ranolazine on AF were included in the meta-analysis. In each of the considered
      studies, a comparison was made between a group of patients taking ranolazine and
      a second group treated instead with another antiarrhythmic therapy, or assigned
      to placebo. Efficacy outcomes were the risk of new-onset AF, the probability of
      conversion to sinus rhythm of patients with recent occurrence (<=48 h) of AF and
      the time to conversion to sinus rhythm. Safety endpoints were death, adverse
      events, QTc prolongation and hypotension. EVIDENCE SYNTHESIS: Ten studies (8 RCTs
      and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine
      was effective in preventing the occurrence of AF when compared to controls
      (RR=0.60; 95% CI: 0.43-0.83; P=0.002). Subgroup analysis showed a more pronounced
      preventive effect of ranolazine against AF in the postoperative setting of
      coronary artery bypass grafting (CABG) surgery (RR=0.39; 95% CI: 0.18-0.83;
      P=0.02) when compared to non-postoperative AF (RR=0.76; 95% CI: 0.63-0.92;
      P=0.04). Ranolazine enhanced the chances of successful cardioversion when added
      to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05
      1.33; P=0.004) and significantly decreased the time to cardioversion (SMD= -10.35
      h; 95% CI: -18.13 hours to -2.57 hours; P<0.001). Overall risks of death, adverse
      events, and QTc prolongation were shown to be similar in the comparison between
      patients treated with ranolazine and controls. CONCLUSIONS: Ranolazine given
      orally at appropriate doses showed the property to significantly quicken the
      conversion of AF to sinus rhythm when combined with the IV amiodarone, compared
      to IV amiodarone alone. Furthermore, in patients in sinus rhythm, ranolazine
      proved to reduce the frequency of new onset AF as well as of its recurrences,
      especially in patients undergone CABG surgery, known to be at high risk of
      developing postoperative AF. In addition, ranolazine use seems to be safe and
      associated with relatively few adverse events.

PMID- 28497942
TI  - Effect of combined resistance and endurance exercise training on regional fat
      loss.
AB  - BACKGROUND: The present study tested the possibility of a localized fat mass (FM)
      reduction by means of training programmes focusing on specific bodily regions.
      METHODS: Sixteen physically inactive women (age: 31+/-4; BMI: 27.5+/-2.1),
      randomly allocated to two groups, completed an 8 week training programme. In one
      group (UpBdResist) training sessions consisted of upper body resistance exercises
      followed by 30-minute cycling at 50%VO2max, while the other group (LwBdResist)
      performed lower body resistance exercises followed by 30 minutes on an arm
      ergometer. Regional body composition was assessed by DEXA and skin fold measures.
      RESULTS: Regardless of a similar reduction in both groups, UpBdResist training
      elicited a greater reduction of the upper limbs (UL) FM as compared to the lower
      limbs (LL) (Delta% UL vs. LL: -12.1+/-3.4 vs. -4.0+/-4.7; P=0.02). Conversely, in
      the LwBdResist group, FM loss was more pronounced in the LL as compared to the UL
      (Delta% UL vs. LL: -2.3+/-7.0 vs. -11.5+/-8.2, P=0.02). Likewise, LwBdResist
      elicited a larger effect on lean mass (LM) of the LL as compared to UL (Delta% LL
      vs. UL: +8.4+/-5.8 vs. -2.7+/-5.0, P<0.01), yet no differences between upper and
      lower limb LM changes were detected in UpBdResist group. CONCLUSIONS: The present
      data suggest that a training programme entailing localized explosive resistance
      exercise, prior to an endurance exercise bout, may target specific adipose tissue
      sites eliciting localised fat mass loss in the upper and lower limbs.

PMID- 28497943
TI  - The effects of over-the-counter jaw-repositioning mouthguards on aerobic
      performance.
AB  - BACKGROUND: Though jaw-repositioning devices have been found to increase size of
      upper respiratory airways in individuals, the effects of jaw-repositioning
      mouthguards on respiratory function during exercise have not been fully explored.
      The purpose of this study is to determine the effects of over-the-counter (OTC)
      jaw-repositioning mouthguards on respiratory function and aerobic performance in
      male athletes. METHODS: College-aged, male athletes (N.=20) participated in this
      randomized, crossover, controlled study. Each subject completed one testing
      session per condition: a no mouthguard control (CON), a placebo mouthguard (PLA),
      an OTC self-adapted jaw-repositioning mouthguard (SA), and an OTC custom-fitted
      jaw-repositioning mouthguard (CF). Each testing session consisted of respiratory
      flow dynamic tests at rest. Ventilation and gas exchange were assessed during a
      graded maximal treadmill test. Peak blood lactate values were obtained from 0-10
      min post-exercise. RESULTS: At rest, the CON had significantly higher peak
      expiratory flow rate values than the other conditions (P<0.03). Maximum voluntary
      ventilation values for PLA and SA were significantly lower compared to CON
      (P<0.02) at rest. No significant differences were observed between conditions for
      ventilation, oxygen consumption, or carbon dioxide production during any
      submaximal stage (P=0.81) nor at maximal aerobic capacity (P=0.35). Peak lactate
      and adjusted peak lactate values were not significantly different between
      conditions (P=0.30 and P=0.63, respectively). CONCLUSIONS: The OTC jaw
      repositioning mouthguards in this study did not enhance aerobic performance. It
      is important to acknowledge that negative effects on aerobic performance were not
      observed, thus providing additional support for encouraging the use of this
      safety device in sports.

PMID- 28497944
TI  - Schedules of Controlled Substances: Temporary Placement of 4-Fluoroisobutyryl
      Fentanyl into Schedule I. Temporary scheduling order.
AB  - The Administrator of the Drug Enforcement Administration is issuing this
      temporary scheduling order to schedule the synthetic opioid, N-(4-fluorophenyl)-N
      (1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyryl fentanyl or para
      fluoroisobutyryl fentanyl), and its isomers, esters, ethers, salts and salts of
      isomers, esters, and ethers, into schedule I pursuant to the temporary scheduling
      provisions of the Controlled Substances Act. This action is based on a finding by
      the Administrator that the placement of 4-fluoroisobutyryl fentanyl into schedule
      I of the Controlled Substances Act is necessary to avoid an imminent hazard to
      the public safety. As a result of this order, the regulatory controls and
      administrative, civil, and criminal sanctions applicable to schedule I controlled
      substances will be imposed on persons who handle (manufacture, distribute,
      reverse distribute, import, export, engage in research, conduct instructional
      activities or chemical analysis, or possess), or propose to handle, 4
      fluoroisobutyryl fentanyl.

PMID- 28497945
TI  - Clarification of Employer's Continuing Obligation To Make and Maintain an
      Accurate Record of Each Recordable Injury and Illness. Final rule.
AB  - Under the Congressional Review Act, Congress has passed, and the President has
      signed, Public Law 115-21, a resolution of disapproval of OSHA's final rule
      titled, "Clarification of Employer's Continuing Obligation to Make and Maintain
      an Accurate Record of each Recordable Injury and Illness." OSHA published the
      rule, which contained various amendments to OSHA's recordkeeping regulations, on
      December 19, 2016. The amendments became effective on January 18, 2017. Because
      Public Law 115-21 invalidates the amendments to OSHA's recordkeeping regulations
      contained in the rule promulgated on December 19, 2016, OSHA is hereby removing
      those amendments from the Code of Federal Regulations.

PMID- 28497946
TI  - Nanopillar Surface Topology Promotes Cardiomyocyte Differentiation through
      Cofilin-Mediated Cytoskeleton Rearrangement.
AB  - Nanoscaled surface patterning is an emerging potential method of directing the
      fate of stem cells. We adopted nanoscaled pillar gradient patterned cell culture
      plates with three diameter gradients [280-360 (GP 280/360), 200-280 (GP 200/280),
      and 120-200 nm (GP 120/200)] and investigated their cell fate-modifying effect on
      multipotent fetal liver kinase 1-positive mesodermal precursor cells (Flk1+ MPCs)
      derived from embryonic stem cells. We observed increased cell proliferation and
      colony formation of the Flk1+ MPCs on the nanopattern plates. Interestingly, the
      200-280 nm-sized (GP 200/280) pillar surface dramatically increased cardiomyocyte
      differentiation and expression of the early cardiac marker gene Mesp1. The
      gradient nanopattern surface-induced cardiomyocytes had cardiac sarcomeres with
      mature cardiac gene expression. We observed Vinculin and p-Cofilin-mediated
      cytoskeleton reorganization during this process. In summary, the gradient
      nanopattern surface with 200-280 nm-sized pillars enhanced cardiomyocyte
      differentiation in Flk1+ MPCs.

PMID- 28497947
TI  - Energy Transfer Kinetics in Photosynthesis as an Inspiration for Improving
      Organic Solar Cells.
AB  - Clues to designing highly efficient organic solar cells may lie in understanding
      the architecture of light-harvesting systems and exciton energy transfer (EET)
      processes in very efficient photosynthetic organisms. Here, we compare the
      kinetics of excitation energy tunnelling from the intact phycobilisome (PBS)
      light-harvesting antenna system to the reaction center in photosystem II in
      intact cells of the cyanobacterium Acaryochloris marina with the charge transfer
      after conversion of photons into photocurrent in vertically aligned carbon
      nanotube (va-CNT) organic solar cells with poly(3-hexyl)thiophene (P3HT) as the
      pigment. We find that the kinetics in electron hole creation following excitation
      at 600 nm in both PBS and va-CNT solar cells to be 450 and 500 fs, respectively.
      The EET process has a 3 and 14 ps pathway in the PBS, while in va-CNT solar cell
      devices, the charge trapping in the CNT takes 11 and 258 ps. We show that the
      main hindrance to efficiency of va-CNT organic solar cells is the slow migration
      of the charges after exciton formation.

PMID- 28497948
TI  - In Situ Visualized Cathode Electrolyte Interphase on LiCoO2 in High Voltage
      Cycling.
AB  - Charging lithium ion battery cathode materials such as LiCoO2 to a higher voltage
      may simultaneously enhance the specific capacity and average operating voltage
      and thus improve the energy density. However, battery cycle life is compromised
      in high voltage cycling due to lattice instability and undesired oxidation of
      electrolyte. Cathode solid-electrolyte interphase (SEI), or cathode-electrolyte
      interphase (CEI), in situ formed at the cathode-electrolyte interface under high
      voltage, is critically important in understanding the cathode degradation process
      and crucial in improving high voltage cycle stability. Here we present in situ
      atomic force microscopy (AFM) investigation of CEI on LiCoO2 at high voltage. The
      formation of CEI is only observed at the LiCoO2 edge plane, not at the basal
      plane. The thin layer of Al2O3 coating completely suppresses the formation of CEI
      at the edge planes, and is shown to significantly improve coin cell high voltage
      cycle stability.

PMID- 28497949
TI  - Addition of Lithium 8-Quinolate into Polyethylenimine Electron-Injection Layer in
      OLEDs: Not Only Reducing Driving Voltage but Also Improving Device Lifetime.
AB  - Solution-processed electron injection layers (EILs) comprising lithium 8
      quinolate (Liq) and polyethylenimine ethoxylated (PEIE) are highly effective for
      enhancing electron injection from ZnO to organic layers and improving device
      lifetime in organic light-emitting devices (OLEDs). Doping of Liq into PEIE
      further reduces the work function of zinc oxide (ZnO) by enhancing dipole
      formation. The intermolecular interaction between Liq and PEIE was elucidated by
      UV-vis absorption measurement and quantum chemical calculation. The OLEDs with
      ZnO covered with PEIE:Liq mixture exhibited lower driving voltage than that of
      the device without Liq. Furthermore, as doping concentration of Liq into PEIE
      increased, the device lifetime and voltage stability during constant current
      operation was successively improved.

PMID- 28497951
TI  - Garnet Solid Electrolyte Protected Li-Metal Batteries.
AB  - Garnet-type solid state electrolyte (SSE) is a promising candidate for high
      performance lithium (Li)-metal batteries due to its good stability and high ionic
      conductivity. One of the main challenges for garnet solid state batteries is the
      poor solid-solid contact between the garnet and electrodes, which results in high
      interfacial resistance, large polarizations, and low efficiencies in batteries.
      To address this challenge, in this work gel electrolyte is used as an interlayer
      between solid electrolyte and solid electrodes to improve their contact and
      reduce their interfacial resistance. The gel electrolyte has a soft structure,
      high ionic conductivity, and good wettability. Through construction of the
      garnet/gel interlayer/electrode structure, the interfacial resistance of the
      garnet significantly decreased from 6.5 * 104 to 248 Omega cm2 for the cathode
      and from 1.4 * 103 to 214 Omega cm2 for the Li-metal anode, successfully
      demonstrating a full cell with high capacity (140 mAh/g for LiFePO4 cathode) over
      70 stable cycles in room temperature. This work provides a binary electrolyte
      consisting of gel electrolyte and solid electrolyte to address the interfacial
      challenge of solid electrolyte and electrodes and the demonstrated hybrid battery
      presents a promising future for battery development with high energy and good
      safety.

PMID- 28497950
TI  - Deamidation Slows Curli Amyloid-Protein Aggregation.
AB  - Nonenzymatic deamidation of asparagine and glutamine in peptides and proteins is
      a frequent modification both in vivo and in vitro. The biological effect is not
      completely understood, but it is often associated with protein degradation and
      loss of biological function. Here we describe the deamidation of CsgA, the major
      protein subunit of curli, which are important proteinaceous components of
      biofilms. CsgA has a high content of Asn and Gln, a feature seen in a few
      proteins that self-aggregate. We have implemented an approach to monitor
      deamidation rapidly by following the globally centroid mass shift, providing
      guidance for studies at the residue level. From the global mass measurement, we
      identified, using LC-MS/MS, extensive deamidation of several Asn residues and
      discovered three "Asn-Gly" sites to be the hottest spots for deamidation. The
      fibrillization of deamidated CsgA was measured using thioflavin T (ThT)
      fluorescence, circular dichroism (CD), and a previously reported hydrogen
      deuterium exchange (HDX) platform. Deamidated proteins exhibit a longer lag phase
      and lower final ThT fluorescence, strongly suggesting slower and less amyloid
      fibril formation. CD spectra show that extensively deamidated CsgA remains
      unstructured and loses its ability to form amyloids. Mass-spectrometry-based HDX
      also shows that deamidated CsgA aggregates more slowly than wild-type CsgA. Taken
      together, the results show that deamidation of CsgA slows its fibrillization and
      disrupts its function, suggesting an opportunity to modulate CsgA fibrillization
      and affect curli and biofilm formation.

PMID- 28497952
TI  - Generalized Subset Designs in Analytical Chemistry.
AB  - Design of experiments (DOE) is an established methodology in research,
      development, manufacturing, and production for screening, optimization, and
      robustness testing. Two-level fractional factorial designs remain the preferred
      approach due to high information content while keeping the number of experiments
      low. These types of designs, however, have never been extended to a generalized
      multilevel reduced design type that would be capable to include both qualitative
      and quantitative factors. In this Article we describe a novel generalized
      fractional factorial design. In addition, it also provides complementary and
      balanced subdesigns analogous to a fold-over in two-level reduced factorial
      designs. We demonstrate how this design type can be applied with good results in
      three different applications in analytical chemistry including (a) multivariate
      calibration using microwave resonance spectroscopy for the determination of water
      in tablets, (b) stability study in drug product development, and (c)
      representative sample selection in clinical studies. This demonstrates the
      potential of generalized fractional factorial designs to be applied in many other
      areas of analytical chemistry where representative, balanced, and complementary
      subsets are required, especially when a combination of quantitative and
      qualitative factors at multiple levels exists.

PMID- 28497953
TI  - Fabrication of Highly Stable Metal Oxide Hollow Nanospheres and Their Catalytic
      Activity toward 4-Nitrophenol Reduction.
AB  - In this paper, hollow nanospheres (HNSs) of metal oxides (NiO, CuO, and NiO/CuO)
      coated with a porous carbon shell (HNSs@C) with good structural stability were
      successfully prepared on the basis of the nanoscale Kirkendall effect. The
      formation process was based on a template-free method, and the as-prepared HNSs@C
      are very clean compared with products of the template process. In addition, the
      results of N2 adsorption-desorption noted that both the metal oxide HNSs and the
      coated carbon were mesoporous structures. Therefore, small molecules can access
      the inner space of the whole HNSs@C, which was expected to increase the active
      site area and to show better performances in applied fields, such as catalysts
      and sensors. As an example of the functional properties, the obtained HNSs@C were
      investigated as the catalyst for the hydrogenation of 4-nitrophenol (4-NP) and
      manifested highly catalytic activity and excellent stability. This work has
      opened up a novel route for the development of metal oxide HNSs nanocatalysts.
      This straightforward method is of significance for development of clean metal
      oxide HNSs with high stability and multiplied applications.

PMID- 28497954
TI  - Metallic Two-Dimensional Nanoframes: Unsupported Hierarchical Nickel-Platinum
      Alloy Nanoarchitectures with Enhanced Electrochemical Oxygen Reduction Activity
      and Stability.
AB  - Electrochemical oxygen reduction reaction (ORR) catalysts that have both high
      activities and long-term stabilities are needed for proton-exchange membrane fuel
      cells (PEMFCs) and metal-air batteries. Two-dimensional (2D) materials based on
      graphene have shown high catalytic activities, however, carbon-based materials
      result in significant catalyst degradation due to carbon oxidation that occurs at
      high electrochemical potentials. Here, we introduce the synthesis and
      electrochemical performance of metallic 2D nanoframes which represent a new
      approach to translate 2D materials into unsupported (carbon-free)
      electrocatalysts that have both significantly higher ORR catalytic activities and
      stabilities compared with conventional Pt/carbon electrocatalysts. Metallic Ni-Pt
      2D nanoframes were synthesized by controlled thermal treatments of Pt-decorated
      Ni(OH)2 nanosheets. The nanoframes consist of a hierarchical 2D framework
      composed of a highly catalytically active Pt-Ni alloy phase with an
      interconnected solid and pore network that results in three-dimensional molecular
      accessibility. The inclusion of Ni within the Pt structure resulted in
      significantly smaller Pt lattice distances compared to those of Pt nanoparticles.
      On the basis of its unique local and extended structure, the ORR specific
      activity of Ni-Pt 2D nanoframes (5.8 mA cmPt-2) was an order of magnitude higher
      than Pt/carbon. In addition, accelerated stability testing at elevated potentials
      up to 1.3 VRHE showed that the metallic Ni-Pt nanoframes exhibit significantly
      improved stability compared with Pt/carbon catalysts. The nanoarchitecture and
      local structure of metallic 2D nanoframes results in high combined specific
      activity and elevated potential stability. Analysis of the ORR electrochemical
      reaction kinetics on the Ni-Pt nanoframes supports that at low overpotentials the
      first electron transfer is the rate-determining step, and the reaction proceeds
      via a four electron reduction process. The ability to create metallic 2D
      structures with 3D molecular accessibility opens up new opportunities for the
      design of high activity and stability carbon-free catalyst nanoarchitectures for
      numerous electrocatalytic and catalytic applications.

PMID- 28497955
TI  - Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases.
AB  - Ammonia-lyases and aminomutases are mechanistically and structurally diverse
      enzymes which catalyze the deamination and/or isomerization of amino acids in
      nature by cleaving or shifting a C-N bond. Of the many protein families in which
      these enzyme activities are found, only a subset have been employed in the
      synthesis of optically pure fine chemicals or in medical applications. This
      review covers the natural diversity of these enzymes, highlighting particular
      enzyme classes that are used within industrial and medical biotechnology. These
      highlights detail the discovery and mechanistic investigations of these
      commercially relevant enzymes, along with comparisons of their various
      applications as stand-alone catalysts, components of artificial biosynthetic
      pathways and biocatalytic or chemoenzymatic cascades, and therapeutic tools for
      the potential treatment of various pathologies.

PMID- 28497956
TI  - Engineering of Heterojunction-Mediated Biointerface for Photoelectrochemical
      Aptasensing: Case of Direct Z-Scheme CdTe-Bi2S3 Heterojunction with Improved
      Visible-Light-Driven Photoelectrical Conversion Efficiency.
AB  - This work presents a heterojunction-mediated photoelectrochemical (PEC)
      biointerface for selective detection of microcystin-LR (MC-LR) by introducing a
      direct Z-scheme heterojunction as efficient visible-light-driven photoactive
      species. Specifically, the Z-scheme type CdTe-Bi2S3 heterojunction was designed
      and synthesized as an ideal photoactive material, which exhibited higher PEC
      activity as compared with either CdTe quantum dots or Bi2S3 nanorods due to the
      improved photogenerated charges separation efficiency of heterojunction. Then the
      MC-LR aptamer was employed for selective recognition of MC-LR target, which was
      immobilized on the CdTe-Bi2S3 film by the formation of phosphor-amidate bonds
      between the phosphate group of aptamer and amino group of the chitosan film on
      the electrode. The proposed aptasensor showed a photocurrent signal due to the
      photoactive CdTe-Bi2S3 heterojunction, while the presence of MC-LR resulted in a
      dose-responsive decrease in PEC response, which allowed the quantification
      analysis of MC-LR by measuring the photocurrent signal of the fabricated
      aptasensor. Under optimal conditions, the resulted PEC aptasensor showed wide
      linear range (0.01-100 pM) and low detection limit (0.005 pM) for MC-LR
      determination with high selectivity and acceptable reproducibility. Finally, the
      proposed aptasensing method was successfully applied in MC-LR detection in real
      water samples.

PMID- 28497957
TI  - Compression Ratio Ion Mobility Programming (CRIMP) Accumulation and Compression
      of Billions of Ions for Ion Mobility-Mass Spectrometry Using Traveling Waves in
      Structures for Lossless Ion Manipulations (SLIM).
AB  - We report on the implementation of a traveling wave (TW) based compression ratio
      ion mobility programming (CRIMP) approach within structures for lossless ion
      manipulations (SLIM) that enables both greatly enlarged trapped ion charge
      capacities and also efficient ion population compression for use in ion mobility
      (IM) separations. Ion accumulation is conducted in a SLIM serpentine ultralong
      path with extended routing (SUPER) region after which CRIMP compression allows
      the large ion populations to be "squeezed". The SLIM SUPER IM module has two
      regions, one operating with conventional traveling waves (i.e., traveling trap;
      TT region) and the second having an intermittently pausing or "stuttering" TW
      (i.e., stuttering trap; ST region). When a stationary voltage profile was used in
      the ST region, ions are blocked at the TT-ST interface and accumulated in the TT
      region and then can be released by resuming a conventional TW in the ST region.
      The population can also be compressed using CRIMP by the repetitive merging of
      ions distributed over multiple TW bins in the TT region into a single TW bin in
      the ST region. Ion accumulation followed by CRIMP compression provides the basis
      for the use of larger ion populations for IM separations. We show that over 109
      ions can be accumulated with high efficiency in the present device and that the
      extent of subsequent compression is only limited by the space charge capacity of
      the trapping region. Approximately 5 * 109 charges introduced from an
      electrospray ionization source were trapped for a 40 s accumulation period, more
      than 2 orders of magnitude greater than the previously reported charge capacity
      of an ion funnel trap. Importantly, we show that extended ion accumulation in
      conjunction with CRIMP compression and multiple passes through the serpentine
      path provides the basis for a highly desirable combination of ultrahigh
      sensitivity and SLIM SUPER high-resolution IM separations.

PMID- 28497958
TI  - Structural Motifs of [Fe(CO2)n]- Clusters (n = 3-7).
AB  - We present IR spectra and quantum chemical calculations for anionic iron-CO2
      clusters of the form [Fe(CO2)n]- (n = 3-7). All observed clusters have at least
      two CO2 units strongly bound to the metal atom. These strongly bound iron-CO2
      complexes form the core ions of the clusters and are solvated by additional,
      weakly bound CO2 molecules. Larger clusters show clear infrared signatures of
      core ion isomers with three CO2 moieties as well. Dominant structural motifs are
      based on bidentate CO2 ligands with Fe-O/Fe-C bonds, oxalate ligands, and metal
      insertion into a CO bond.

PMID- 28497959
TI  - Characterization of Agronomy, Grain Physicochemical Quality, and Nutritional
      Property of High-Lysine 35R Transgenic Rice with Simultaneous Modification of
      Lysine Biosynthesis and Catabolism.
AB  - Lysine is the first limiting essential amino acid in rice. We previously
      constructed a series of transgenic rice lines to enhance lysine biosynthesis
      (35S), down-regulate its catabolism (Ri), or simultaneously achieve both
      metabolic effects (35R). In this study, nine transgenic lines, three from each
      group, were selected for both field and animal feeding trials. The results showed
      that the transgene(s) caused no obvious effects on field performance and main
      agronomic traits. Mature seeds of transgenic line 35R-17 contained 48-60-fold
      more free lysine than in wild type and had slightly lower apparent amylose
      content and softer gel consistency. Moreover, a 35-day feeding experiment showed
      that the body weight gain, food efficiency, and protein efficiency ratio of rats
      fed the 35R-17 transgenic rice diet were improved when compared with those fed
      wild-type rice diet. These data will be useful for further evaluation and
      potential commercialization of 35R high-lysine transgenic rice.

PMID- 28497961
TI  - Evaluating the Development of Biocatalytic Technology for the Targeted Removal of
      Perchlorate from Drinking Water.
AB  - Removing micropollutants is challenging in part because of their toxicity at low
      concentrations. A biocatalytic approach could harness the high affinity of
      enzymes for their substrates to address this challenge. The potential of
      biocatalysis relative to mature (nonselective ion exchange, selective ion
      exchange, and whole-cell biological reduction) and emerging (catalysis)
      perchlorate-removal technologies was evaluated through a quantitative sustainable
      design framework, and research objectives were prioritized to advance economic
      and environmental sustainability. In its current undeveloped state, the
      biocatalytic technology was approximately 1 order of magnitude higher in cost and
      environmental impact than nonselective ion exchange. Biocatalyst production was
      highly correlated with cost and impact. Realistic improvement scenarios targeting
      biocatalyst yield, biocatalyst immobilization for reuse, and elimination of an
      electron shuttle could reduce total costs to $0.034 m-3 and global warming
      potential (GWP) to 0.051 kg CO2 eq m-3: roughly 6.5% of cost and 7.3% of GWP of
      the background from drinking water treatment and competitive with the best
      performing technology, selective ion exchange. With less stringent perchlorate
      regulatory limits, ion exchange technologies had increased cost and impact, in
      contrast to biocatalytic and catalytic technologies. Targeted advances in
      biocatalysis could provide affordable and sustainable treatment options to
      protect the public from micropollutants.

PMID- 28497960
TI  - Using Dynamic Covalent Chemistry To Drive Morphological Transitions: Controlled
      Release of Encapsulated Nanoparticles from Block Copolymer Vesicles.
AB  - Dynamic covalent chemistry is exploited to drive morphological order-order
      transitions to achieve the controlled release of a model payload (e.g., silica
      nanoparticles) encapsulated within block copolymer vesicles. More specifically,
      poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA)
      diblock copolymer vesicles were prepared via aqueous polymerization-induced self
      assembly in either the presence or absence of silica nanoparticles. Addition of 3
      aminophenylboronic acid (APBA) to such vesicles results in specific binding of
      this reagent to some of the pendent cis-diol groups on the hydrophilic PGMA
      chains to form phenylboronate ester bonds in mildly alkaline aqueous solution (pH
      ~ 10). This leads to a subtle increase in the effective volume fraction of this
      stabilizer block, which in turn causes a reduction in the packing parameter and
      hence induces a vesicle-to-worm (or vesicle-to-sphere) morphological transition.
      The evolution in copolymer morphology (and the associated sol-gel transitions)
      was monitored using dynamic light scattering, transmission electron microscopy,
      oscillatory rheology, and small-angle X-ray scattering. In contrast to the
      literature, in situ release of encapsulated silica nanoparticles is achieved via
      vesicle dissociation at room temperature; moreover, the rate of release can be
      fine-tuned by varying the solution pH and/or the APBA concentration. Furthermore,
      this strategy also works (i) for relatively thick-walled vesicles that do not
      normally exhibit stimulus-responsive behavior and (ii) in the presence of added
      salt. This novel molecular recognition strategy to trigger morphological
      transitions via dynamic covalent chemistry offers considerable scope for the
      design of new stimulus-responsive copolymer vesicles (and hydrogels) for targeted
      delivery and controlled release of cargoes. In particular, the conditions used in
      this new approach are relevant to liquid laundry formulations, whereby enzymes
      require protection to prevent their deactivation by bleach.

PMID- 28497962
TI  - Potential of Polygonum cuspidatum Root as an Antidiabetic Food: Dual High
      Resolution alpha-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC
      HRMS and NMR for Identification of Antidiabetic Constituents.
AB  - The worldwide increasing incidence of type 2 diabetes has fueled an intensified
      search for food and herbal remedies with preventive and/or therapeutic
      properties. Polygonum cuspidatum Siebold & Zucc. (Polygonaceae) is used as a
      functional food in Japan and South Korea, and it is also a well-known traditional
      antidiabetic herb used in China. In this study, dual high-resolution alpha
      glucosidase and protein-tyrosine phosphatase 1B (PTP1B) inhibition profiling was
      used for the identification of individual antidiabetic constituents directly from
      the crude ethyl acetate extract and fractions of P. cuspidatum. Subsequent
      preparative-scale HPLC was used to isolate a series of alpha-glucosidase
      inhibitors, which after HPLC-HRMS and NMR analysis were identified as procyanidin
      B2 3,3"-O-digallate (3) and (-)-epicatechin gallate (5) with IC50 values of 0.42
      +/- 0.02 and 0.48 +/- 0.0004 MUM, respectively, as well as a series of stilbene
      analogues with IC50 value in the range from 6.05 +/- 0.05 to 116.10 +/- 2.04 MUM.
      In addition, (trans)-emodin-physcion bianthrone (15b) and (cis)-emodin-physcion
      bianthrone (15c) were identified as potent PTP1B inhibitors with IC50 values of
      2.77 +/- 1.23 and 7.29 +/- 2.32 MUM, respectively. These findings show that P.
      cuspidatum is a potential functional food for management of type 2 diabetes.

PMID- 28497963
TI  - IR Spectra of n-Bu4M (M = Si, Ge, Sn, Pb), n-BuAuPPh3-d15, and "n-Bu" on a Gold
      Surface.
AB  - Observed and DFT-calculated IR spectra of n-Bu4M (M = Si, Ge, Sn, Pb),
      (CH3CH2CH213CD2)4Sn, and n-BuAuPPh3-d15 are reported and assigned. The asymmetric
      CH stretching vibration of the CH2 group adjacent to the metal atom appears as a
      distinct shoulder at ~2934 cm-1, whereas for other CH2 groups it is located at
      ~2922 cm-1. The characteristic peak at ~2899 cm-1 is attributed to an overtone of
      a symmetric CH2 bend at ~1445 cm-1. In n-BuAuPPh3-d15, the CH stretching
      vibrations of the butyl group are shifted to lower frequencies by ~10 cm-1, and
      two possible rationalizations are offered.

PMID- 28497964
TI  - Biosynthetic Origin of the Hydroxamic Acid Moiety of Trichostatin A:
      Identification of Unprecedented Enzymatic Machinery Involved in Hydroxylamine
      Transfer.
AB  - Trichostatin A (TSA) is widely used in the field of epigenetics because it
      potently inhibits histone deacetylase (HDAC). In-depth studies have revealed that
      the hydroxamic acid group in TSA chelates the zinc(II) ion in the active site of
      HDAC to realize the inhibitory activity. Here we report the first identification
      of a complete TSA biosynthetic gene cluster from Streptomyces sp. RM72 and the
      heterologous production of TSA in Streptomyces albus. Biochemical analyses
      unambiguously demonstrate that unprecedented biosynthetic machinery catalyzes the
      direct transfer of hydroxylamine from a nonproteinogenic amino acid, l-glutamic
      acid gamma-monohydroxamate, to the carboxylic acid group of trichostatic acid to
      form the hydroxamic acid moiety of TSA. The present study establishes the
      biosynthetic pathway of TSA, paving the way toward understanding the biosynthesis
      of other hydroxamic acid-containing natural products.

PMID- 28497965
TI  - Residues of Alpha Helix H3 Determine Distinctive Features of Transforming Growth
      Factor beta3.
AB  - Transforming growth factors (TGF-betas) are proteins that regulate cell growth by
      binding to their receptors. In contrast to transforming growth factor (TGF)
      beta1, TGF-beta3 homodimer is believed to exist also in an open conformation, in
      which both of its monomers are loosely packed against each other. At the origin
      of this difference is the H3-helix. Its sequence and degree of structuration seem
      to govern the outcome of TGF dimerization. We docked two monomers of TGF-beta3
      with intact and altered H3 alpha-helix against each other using HADDOCK. TGF
      beta3 monomer with an intact H3-helix exclusively forms closed conformations of
      homodimer, whereas the open conformation may coexist with the closed one when a
      part of the H3 alpha-helix is destabilized. We quantify the difference in its
      conformational preference for the open versus the closed structure by calculating
      the binding energy between monomers using the MMPBSA approach. We compare the
      wild type (wt) TGFbeta3/TGFbeta1 homodimers in the Protein Data Bank to a swapped
      mutant where all residues of the H3-helix were mutated to the respective
      TGFbeta1/TGFbeta3 sequence. Swapping stabilizes the closed conformation and
      destabilizes the open conformation of TGFbeta3. Further detailed insight is
      derived from molecular dynamics simulation studies suggesting that Val 61 of the
      H3-helix may act as an anchor residue for the closed conformation of TGFbeta3.
      Computational alanine scanning mutagenesis confirms that several residues of the
      H3-helix are the hot residues for the closed conformation of TGFbeta3. These
      observations may bear relevance to general conformational transitions in proteins
      and specifically in the TGFbeta superfamily.

PMID- 28497966
TI  - Large-Scale Analysis of Hydrogen Bond Interaction Patterns in Protein-Ligand
      Interfaces.
AB  - Protein-ligand interactions are the fundamental basis for molecular design in
      pharmaceutical research, biocatalysis, and agrochemical development. Especially
      hydrogen bonds are known to have special geometric requirements and therefore
      deserve a detailed analysis. In modeling approaches a more general description of
      hydrogen bond geometries, using distance and directionality, is applied. A first
      study of their geometries was performed based on 15 protein structures in 1982.
      Currently there are about 95 000 protein-ligand structures available in the PDB,
      providing a solid foundation for a new large-scale statistical analysis. Here, we
      report a comprehensive investigation of geometric and functional properties of
      hydrogen bonds. Out of 22 defined functional groups, eight are fully in
      accordance with theoretical predictions while 14 show variations from expected
      values. On the basis of these results, we derived interaction geometries to
      improve current computational models. It is expected that these observations will
      be useful in designing new chemical structures for biological applications.

PMID- 28497967
TI  - Interactions of Metal-Based and Ligand-Based Electronic Spins in Neutral
      Tripyrrindione pi Dimers.
AB  - The ability of tetrapyrrolic macrocycles to stabilize unpaired electrons and
      engage in pi-pi interactions is essential for many electron-transfer processes in
      biology and materials engineering. Herein, we demonstrate that the formation of
      pi dimers is recapitulated in complexes of a linear tripyrrolic analogue of
      naturally occurring pigments derived from heme decomposition.
      Hexaethyltripyrrindione (H3TD1) coordinates divalent transition metals (i.e., Pd,
      Cu, Ni) as a stable dianionic radical and was recently described as a robust
      redox-active ligand. The resulting planar complexes, which feature a delocalized
      ligand-based electronic spin, are stable at room temperature in air and support
      ligand-based one-electron processes. We detail the dimerization of neutral
      tripyrrindione complexes in solution through electron paramagnetic resonance
      (EPR) and visible absorption spectroscopic methods. Variable-temperature
      measurements using both EPR and absorption techniques allowed determination of
      the thermodynamic parameters of pi dimerization, which resemble those previously
      reported for porphyrin radical cations. The inferred electronic structure,
      featuring coupling of ligand-based electronic spins in the pi dimers, is
      supported by density functional theory (DFT) calculations.

PMID- 28497968
TI  - Chemoenzymatic Synthesis and alpha-Glucosidase Inhibitory Activity of Dimeric
      Neolignans Inspired by Magnolol.
AB  - A chemoenzymatic synthesis of a small library of dimeric neolignans inspired by
      magnolol (1) is reported. The 2-iodoxybenzoic acid (IBX)-mediated regioselective
      ortho-hydroxylation of magnolol is described, affording the bisphenols 6 and 7.
      Further magnolol analogues (12, 13, 15-17, 19-23) were obtained from eugenol (3),
      tyrosol (4), and homovanillic alcohol (5), through horseradish peroxidase (HRP)
      mediated oxidative coupling and regioselective ortho-hydroxylation or ortho
      demethylation in the presence of IBX, followed by reductive treatment with
      Na2S2O4. A chemoselective protection/deprotection of the alcoholic group of 4 and
      5 was carried out by lipase-mediated acetylation/deacetylation. The dimeric
      neolignans, together with 1 and honokiol (2), were evaluated as inhibitors of
      yeast alpha-glucosidase, in view of their possible utilization and optimization
      as antidiabetic drugs. The synthetic analogues of magnolol showed a strong
      inhibitory activity with IC50 values in the range 0.15-4.1 MUM, much lower than
      those of honokiol and the reference compounds quercetin and acarbose. In
      particular, a very potent inhibitory activity, with an IC50 of 0.15 MUM, was
      observed for 1,1'-dityrosol-8,8'-diacetate (15), and comparable inhibitory
      activities were also shown by bisphenols 6 (0.49 MUM), 13 (0.50 MUM), and 22
      (0.86 MUM). A kinetic study showed that 15 acts as a competitive inhibitor, with
      a Ki value of 0.86 MUM.

PMID- 28497969
TI  - Synthesis of Benzoquinolizinium Salts by Rh(III)-Catalyzed Cascade Double N
      Annulation Reactions of Allylamines, Diarylacetylenes, and HBF4.
AB  - A new cascade double N-annulation method has been developed for the synthesis of
      benzoquinolizinium salts. The process takes place between allylamines, internal
      alkynes, and HBF4 in the presence of Rh(III)/Cu(II) complexes and leads to
      formation of multisubstituted benzoquinolizinium salts. Importantly, the
      resulting benzoquinolizinium salts serve as fluorescent materials whose emission
      wavelengths can be tuned by selection of appropriate substituents.

PMID- 28497970
TI  - Electrowetting of Weak Polyelectrolyte-Coated Surfaces.
AB  - Polymer coatings are commonly used to modify interfacial properties like
      wettability, lubrication, or biocompatibility. These properties are determined by
      the conformation of polymer molecules at the interface. Polyelectrolytes are
      convenient elementary bricks to build smart materials, given that polyion chain
      conformation is very sensitive to different environmental variables. Here we
      discuss the effect of an applied electric field on the properties of surfaces
      coated with poly(acrylic acid) brushes. By combining atomic force microscopy,
      quartz crystal microbalance, and contact angle experiments, we show that it is
      possible to precisely tune polyion chain conformation, surface adhesion, and
      surface wettability using very low applied voltages if the polymer grafting
      density and environmental conditions (pH and ionic strength) are properly
      formulated. Our results indicate that the effective ionization degree of the
      grafted weak polyacid can be finely controlled with the externally applied field,
      with important consequences for the macroscopic surface properties.

PMID- 28497971
TI  - 9,9-Difluorobispidine Analogues of Cisplatin, Carboplatin, and Oxaliplatin.
AB  - As part of a comprehensive study of N-unsubstituted bispidines, the novel 9,9
      difluorobispidine (D) has been synthesized. The compound crystallizes from
      pentane below 0  degrees C in the ordered-crystalline phase D-II and undergoes at
      0-30  degrees C a stepwise endothermic phase transition to a dynamically
      disordered crystalline phase D-I; melting occurs at 227  degrees C. Single
      crystalline D-II has been subjected to X-ray structure analysis, revealing
      association of the molecules to form chains. Reaction of (1,5-hexadiene)PtCl2
      with D affords {C7H10F2(NH)2}PtCl2 (D1), which can be converted by conventional
      routes to {C7H10F2(NH)2}Pt(cbdca).5H2O (D2) and {C7H10F2(NH)2}Pt(C2O4) (D3).
      Compound D1 crystallizes solvent-free from water and is isomorphous to the
      solvent-free parent bispidine analogue (A1). The pentahydrate D2 is isomorphous
      to the bispidine and 9-oxabispidine homologues (A2 and C2), as shown by X-ray
      structure analyses. An increased polarity of the bispidine skeleton as a
      consequence of the high electronegativity of fluorine is seen as the reason for
      low cytotoxic potency of D1-D3.

PMID- 28497972
TI  - Organocatalytic Asymmetric Annulation between Hydroxymaleimides and
      Nitrosoarenes: Stereoselective Preparation of Chiral Quaternary N
      Hydroxyindolines.
AB  - An unusual and highly effective asymmetric annulation of nitrosoarenes with
      hydroxymaleimides catalyzed by a chiral bifunctional amine squaramide catalyst
      has been disclosed. A wide range of highly fused chiral N-hydroxyindolines with
      two consecutive quaternary stereocenters and multifunctional groups were directly
      and effectively prepared in excellent yields (up to >99%) with complete
      regioselective cyclization and excellent stereoselectivities (up to >99:1 dr and
      >99% ee). The efficiency and potentials of the new reaction and the target chiral
      entities were well demonstrated by delicate transformations into a series of new
      chiral indolines.

PMID- 28497973
TI  - Construction of Chiral-Fused Tricyclic gamma-Lactams via a trans-Perhydroindolic
      Acid-Catalyzed Asymmetric Domino Reaction.
AB  - An asymmetric domino reaction was developed utilizing readily available cyclic
      alpha-dehydroamino ketones and aldehydes, which when subjected a 2-iodoxybenzoic
      acid (IBX)-mediated oxidation gives pyrrolidinone-containing tricyclic
      derivatives. trans-Perhydroindolic acid proved to be an efficient organocatalyst
      in this reaction (up to 94% yield, 99% ee, and >20:1 dr). The product could be
      conveniently converted to synthetically useful intermediates via simple
      transformations. A possible stereocontrolled process has been suggested according
      to X-ray crystallography studies.

PMID- 28497974
TI  - Carbon Nanotube and Semiconductor Nanorods Hybrids: Preparation,
      Characterization, and Evaluation of Photocurrent Generation.
AB  - Carbon nanotubes (CNTs) and semiconductor nanocrystals (SCNCs) are known to be
      interesting donor-acceptor partners due to their unique optical and electronic
      properties. These exciting features have led to the development of novel
      composites based on these two nanomaterials and to their characterization for use
      in various applications, such as components in sensors, transistors, solar cells
      and biomedical devices. Two approaches based on covalent and noncovalent methods
      have been suggested for coupling the SCNCs to CNTs. Most covalent conjugation
      methods used so far were found to disrupt the electronic structure of the CNTs or
      interfere with charge transfer in the CNT-SCNC interface. Moreover, it offers
      random and poorly organized nanoparticle coatings. Therefore, noncovalent methods
      are considered to be ideal for better electronic coupling. However, a key common
      drawback of noncovalent methods is the lack of stability which hampers their
      applicability. In this article, a method has been developed to couple
      semiconductor seeded nanorods onto CNTs through pi-pi interactions. The CNTs and
      pyrene conjugated SCNC hybrid materials were characterized by both microscopic
      and spectroscopic techniques. Fluorescence and photocurrent measurements suggest
      the proposed pi-stacking approach results in a strong electronic coupling between
      the CNTs and the SCNCs leading to better photocurrent efficiency than that of a
      covalent conjugation method reported using similar SCNC material. Overall, the
      CNT-SCNC films reported in the present study open the scope for the fabrication
      of optoelectronic devices for various applications.

PMID- 28497976
TI  - Copper(I)-Catalyzed Interrupted Click Reaction with TMSCF3: Synthesis of 5
      Trifluoromethyl 1,2,3-Triazoles.
AB  - We herein describe a Cu(I)-catalyzed interrupted click reaction, using
      (trifluoromethyl)trimethylsilane (TMSCF3) as a nucleophilic CF3 source, to
      synthesize 5-trifluoromethyl 1,2,3-triazoles in one step from readily available
      terminal alkynes and azides. The reaction shows complete regioselectivity, broad
      substrate scope, and good functional group tolerability. The application of the
      reaction has been demonstrated in the synthesis of a trifluoromethylated analog
      of antiepileptic drug rufinamide.

PMID- 28497975
TI  - Adjuvants Based on Synthetic Mycobacterial Cord Factor Analogues: Biophysical
      Properties of Neat Glycolipids and Nanoself-Assemblies with DDA.
AB  - Synthetic mycobacterial cord factor analogues, e.g., trehalose 6,6'-dibehenate
      (TDB), are highly promising adjuvants due to their strong immunopotentiating
      capabilities, but their biophysical properties have remained poorly
      characterized. Here, we report the synthesis of an array of synthetic TDB
      analogues varying in acyl chain length, degree of acylation, and headgroup
      display, which was subjected to biophysical characterization of neat nondispersed
      self-assembled nanostructures in excess buffer and as aqueous dispersions with
      cationic dimethyldioctadecylammonium (DDA) bromide. The array comprised trehalose
      mono- (TMX) and diester (TDX) analogues with symmetrically shortened acyl chains
      [denoted by X: arachidate (A), stearate (S), palmitate (P), myristate (Myr), and
      laurate (L)] and an analogue with a short hydrophilic polyethylene glycol (PEG)
      linker inserted between the trehalose headgroup of TDS and the acyl chains (PEG
      TDS). All dispersions were liposomes, but in contrast to the colloidally stable
      and highly cationic TDX-containing liposomes, the zeta-potential was
      significantly reduced for DDA/TMX and DDA/PEG-TDS liposomes, suggesting a charge
      shielding effect, which compromises the colloidal stability. An increased d
      spacing was observed for the lamellar phase of neat TDB analogues in excess
      buffer (TDS < TMS < PEG-TDS), confirming that the charge shielding is caused by
      an extended molecular configuration of the more flexible headgroup. Differential
      scanning calorimetry showed highly cooperative phase transitions for all tested
      dispersions albeit the monoesters destabilized the lipid bilayers. Langmuir
      experiments demonstrated that incorporation of TDXs and PEG-TDS stabilized DDA
      monolayers due to improved hydrogen bonding and reduced intermolecular
      repulsions. In conclusion, data suggest that the DDA/TDS dispersions exhibit
      favorable physicochemical properties rendering these DDA/TDS liposomes an
      attractive vaccine adjuvant, and they emphasize that not only the receptor
      binding and immune activation but also the biophysical properties of
      immunopotentiator formulations should be collectively considered when designing
      adjuvants with optimal safety, efficacy, and storage stability.

PMID- 28497977
TI  - Effect of Amino Acid Substitutions Within the V3 Region of HIV-1 CRF01_AE on
      Interaction with CCR5-Coreceptor.
AB  - Specific amino acids within the V3 loop of HIV-1 CRF01_AE envelope glycoprotein
      that are involved in the interaction with CCR5/CXCR4 coreceptors, are not well
      characterized. We generated V3 mutants using polymerase chain reaction (PCR)
      based site-directed mutagenesis of HIV-1 CRF01_AE R5-env plasmids at specific
      positions. Mutant viruses were produced by env-pseudotyped virus assay, tested
      for coreceptor usage using U373.R5 and U373.X4 cells, and viral entry was
      assessed with luciferase activity measurement. All viruses, harboring either
      single or double mutations, used the CCR5 coreceptor. However, those containing a
      single substitution at positions 7, 11, 18, and 32 and those with mutations at
      positions 5/32 and 18/32 had reduced infectivity. Only virus with arginine
      substitution at position 11 seemed to be involved in CXCR4 coreceptor usage. Our
      results suggest that some V3 positions may be necessary for the binding to
      coreceptor, but not for the switch of coreceptor usage.

PMID- 28497978
TI  - Extraction and Quantitation of Nicotinamide Adenine Dinucleotide Redox Cofactors.
AB  - AIMS: Accurate analysis of dinucleotide redox cofactors nicotinamide adenine
      dinucleotide phosphate reduced (NADPH), nicotinamide adenine dinucleotide
      phosphate (NADP+), nicotinamide adenine dinucleotide reduced (NADH), and
      nicotinamide adenine dinucleotide (NAD+) from biological samples is important to
      understanding cellular redox homeostasis. In this study, we aimed to develop a
      simple protocol for quenching metabolism and extracting NADPH that avoids
      interconversion among the reduced forms and the oxidized forms. RESULTS: We
      compared seven different solvents for quenching and extraction of cultured
      mammalian cells and mouse tissues: a cold aqueous buffer commonly used in enzyme
      assays with and without detergent, hot aqueous buffer, and cold organic mixtures
      (80% methanol, buffered 75% acetonitrile, and acidic 40:40:20
      acetonitrile:methanol:water with either 0.02 M or 0.1 M formic acid). Extracts
      were analyzed by liquid chromatography-mass spectrometry (LC-MS). To monitor the
      metabolite interconversion, cells were grown in 13C6-glucose medium, and
      unlabeled standards were spiked into the extraction solvents. Interconversion
      between the oxidized and reduced forms was substantial except for the enzyme
      assay buffer with detergent, 80% methanol and 40:40:20
      acetonitrile:methanol:water, with the 0.1 M formic acid mix giving the least
      interconversion and best recoveries. Absolute NAD+, NADH, NADP+, and NADPH
      concentrations in cells and mouse tissues were measured with this approach.
      INNOVATION: We found that the interconversion between the reduced and oxidized
      forms during extraction is a major barrier to accurately measuring NADPH/NADP+
      and NADH/NAD+ ratios. Such interconversion can be monitored by isotope labeling
      cells and spiking NAD(P)(H) standards. CONCLUSION: Extraction with 40:40:20
      acetonitrile:methanol:water with 0.1 M formic acid decreases interconversion and,
      therefore, is suitable for measurement of redox cofactor ratios using LC-MS. This
      solvent is also useful for general metabolomics. Samples should be neutralized
      immediately after extraction to avoid acid-catalyzed degradation. When LC-MS is
      not available and enzyme assays are accordingly used, inclusion of detergent in
      the aqueous extraction buffer reduces interconversion. Antioxid. Redox Signal.
      28, 167-179.

PMID- 28497979
TI  - Sensitive Detection of Rhodamine B in Condiments Using Surface-Enhanced Resonance
      Raman Scattering (SERRS) Silver Nanowires as Substrate.
AB  - In this paper, a facile large-scale preparation of surface-enhanced resonance
      Raman scattering (SERRS) substrates for the determination of Rhodamine B (RhB)
      based on silver nanowires (Ag NWs) has been developed. The morphology, structure,
      and properties of as-prepared Ag NWs are characterized using ultraviolet-visible
      (UV-Vis) spectroscopy, field emission scanning electron microscopy (FE-SEM), and
      X-ray diffraction (XRD), respectively. Ag NWs were assembled onto glass slides
      through a self-assembly method. Moreover, in our experiment, as-prepared Ag
      NWs@glass were used as a SERRS substrate to detect RhB at the excitation
      wavelength of 532 nm. Experimental conditions such as pH value and soaking time
      on SERRS performance were studied and optimized. Under the optimized conditions,
      the SERRS intensity at 1648 cm-1 exhibited a linear relationship with the
      concentration of RhB in the range of 1.0 * 10-9-1.0 * 10-5 mol L-1 and detection
      limit (signal-to-noise ratio [S/N] = 3) is as low as 0.3 nmol L-1. The
      corresponding correlation coefficient of the linear equation was 0.996. This
      method based on Ag NWs@glass for the detection of RhB in three kinds of condiment
      was investigated. The limits of detection (LODs) for RhB were 0.35 ug/g in chili
      powder, 0.14 ug/g in chili sauce, and 0.02 ug/g in Chinese prickly ash. The
      relative standard deviations (RSD) were between 2.18% and 4.56% (n = 3) and
      recoveries at three levels were in the range of 80.0-98.7% for different spiked
      food products. Moreover, the results showed that the proposed method was
      sensitive, convenient, and feasible for the determination of RhB in condiments.

PMID- 28497980
TI  - The association between cigarette smoking, virologic suppression, and CD4+
      lymphocyte count in HIV-Infected Russian women.
AB  - Cigarette smoking among people living with HIV/AIDS is associated with
      significant morbidity and mortality, but findings regarding the association
      between cigarette smoking and HIV viral load and CD4+ lymphocyte counts have been
      inconsistent. This study characterized the prevalence of cigarette smoking among
      HIV-infected Russian women and examined the association between smoking frequency
      and quantity and HIV viral load and CD4+ lymphocyte counts. HIV-infected Russian
      women (N = 250; M age = 30.0) in St. Petersburg, Russia, completed an audio
      computer-assisted self-interview survey assessing cigarette use, antiretroviral
      medication adherence, and provided blood samples assayed for HIV viral load and
      CD4+ lymphocyte counts. The majority (60.4%) reported cigarette smoking in the
      past month; 49.0% of recent smokers were classified as moderate or heavy smokers,
      defined as smoking >=10 cigarettes daily. Viral load status did not differ
      between infrequent smokers and regular smokers. However, moderate/heavy smokers
      (relative to light smokers) were more likely to have a detectable viral load (AOR
      = 2.3, 95% CI: 1.1, 5.1). There were no significant differences in CD4+
      lymphocyte counts by smoking frequency or quantity of cigarettes smoked. Results
      highlight the need for additional research to examine the association between
      cigarette smoking and virologic suppression and markers of HIV disease
      progression. Adverse health consequences of cigarette smoking coupled with a
      potential link between heavy smoking and poor virologic suppression highlight the
      need for assessment of cigarette use and provision of evidence-based smoking
      cessation interventions within HIV medical care.

PMID- 28497981
TI  - Measurement of Cerium and Gadolinium in Solid Lithium Chloride-Potassium Chloride
      Salt Using Laser-Induced Breakdown Spectroscopy (LIBS).
AB  - Pyroprocessing of used nuclear fuel (UNF) has many advantages-including that it
      is proliferation resistant. However, as part of the process, special nuclear
      materials accumulate in the electrolyte salt and present material accountability
      and safeguards concerns. The main motivation of this work was to explore a laser
      induced breakdown spectroscopy (LIBS) approach as an online monitoring technique
      to enhance the material accountability of special nuclear materials in
      pyroprocessing. In this work, a vacuum extraction method was used to draw the
      molten salt (CeCl3-GdCl3-LiCl-KCl) up into 4 mm diameter Pyrex tubes where it
      froze. The salt was then removed and the solid salt was measured using LIBS and
      inductively coupled plasma mass spectroscopy (ICP-MS). A total of 36 samples were
      made that varied the CeCl3 and GdCl3 (surrogates for uranium and plutonium,
      respectively) concentrations from 0.5 wt% to 5 wt%. From these samples,
      univariate calibration curves for Ce and Gd were generated using peak area and
      peak intensity methods. For Ce, the Ce 551.1 nm line using the peak area provided
      the best calibration curve with a limit of detection (LOD) of 0.099 wt% and a
      root mean squared error of cross-validation (RMSECV) of 0.197 wt%. For Gd, the
      best curve was generated using the peak intensities of the Gd 564.2 nm line
      resulting in a LOD of 0.027 wt% and a RMSECV of 0.295 wt%. The RMSECV for the
      univariate cases were determined using leave-one-out cross-validation. In
      addition to the univariate calibration curves, partial least squares (PLS)
      regression was done to develop a calibration model. The PLS models yielded
      similar results with RMSECV (determined using Venetian blind cross-validation
      with 17% left out per split) values of 0.30 wt% and 0.29 wt% for Ce and Gd,
      respectively. This work has shown that solid pyroprocessing salt can be
      qualitatively and quantitatively monitored using LIBS. This work has the
      potential of significantly enhancing the material monitoring and safeguards of
      special nuclear materials in pyroprocessing.

PMID- 28497983
TI  - Promoting Responsible Electronic Documentation: Validity Evidence for a Checklist
      to Assess Progress Notes in the Electronic Health Record.
AB  - : Construct: We aimed to develop an instrument to measure the quality of
      inpatient electronic health record- (EHR-) generated progress notes without
      requiring raters to review the detailed chart or know the patient. BACKGROUND:
      Notes written in EHRs have generated criticism for being unnecessarily long and
      redundant, perpetuating inaccuracy and obscuring providers' clinical reasoning.
      Available assessment tools either focus on outpatient progress notes or require
      chart review by raters to develop familiarity with the patient. APPROACH: We used
      medical literature, local expert review, and attending focus groups to develop
      and refine an instrument to evaluate inpatient progress notes. We measured
      interrater reliability and scored the selected-response elements of the checklist
      for a sample of 100 progress notes written by PGY-1 trainees on the general
      medicine service. RESULTS: We developed an instrument with 18 selected-response
      items and four open-ended items to measure the quality of inpatient progress
      notes written in the EHR. The mean Cohen's kappa coefficient demonstrated good
      agreement at .67. The mean note score was 66.9% of maximum possible points (SD =
      10.6, range = 34.4%-93.3%). CONCLUSIONS: We present validity evidence in the
      domains of content, internal structure, and response process for a new checklist
      for rating inpatient progress notes. The scored checklist can be completed in
      approximately 7 minutes by a rater who is not familiar with the patient and can
      be done without extensive chart review. We further demonstrate that trainee notes
      show substantial room for improvement.

PMID- 28497985
TI  - Examining Medical Student Specialty Choice Through a Gender Lens: An
      Orientational Qualitative Study.
AB  - : Phenomenon: A growing number of women are entering the medical workforce, yet
      their distribution across medical specialties remains nonuniform. We sought to
      describe how culture, bias, and socialization shape gendered thinking regarding
      specialty choice at a Canadian undergraduate medical institution. APPROACH: We
      analyzed transcripts from the Career Choices Project: 16 semistructured focus
      group discussions with 70 students graduating from Memorial University of
      Newfoundland in 2003, 2006, 2007, and 2008. The questions and prompts were
      designed to explore factors influencing specialty choice and did not specifically
      probe gender-based experiences. Focus groups were audio-recorded, transcribed,
      and deidentified before analysis. Analysis was inductive and guided by principles
      of orientational qualitative inquiry using a gender-specific lens. FINDINGS: The
      pursuits of personal and professional goals, as well as contextual factors, were
      the major themes that influenced decision-making for women and men. Composition
      of these major themes varied between genders. Influence of a partner,
      consideration of familial commitments (both present and future), feeling a sense
      of connectedness with the field in question, and social accountability were
      described by women as important. Both genders hoped to pursue careers that would
      afford "flexibility" in order to balance work with their personal lives, though
      the construct of work-life balance differed between genders. Women did not
      explicitly identify gender bias or sexism as influencing factors, but their
      narratives suggest that these elements were at play. Insights: Our findings
      suggest that unlike men, women's decision-making is informed by tension between
      personal and professional goals, likely related to the context of gendered
      personal and societal expectations.

PMID- 28497984
TI  - Recovery of Working Memory Following Pediatric Traumatic Brain Injury: A
      Longitudinal Analysis.
AB  - In a prospective longitudinal study, the trajectory of verbal and visual-spatial
      working memory (WM) development was examined 2-, 6-, 12-, and 24-months following
      complicated-mild to severe pediatric traumatic brain injury (TBI; n = 55)
      relative to an orthopedic injury comparison group (n = 47). Individual growth
      curve modeling revealed an interaction of age, severity, and time for verbal, but
      not visual-spatial WM. The youngest children with severe TBI had the lowest
      scores and slowest verbal WM growth. WM outcome is best understood in light of
      age at injury and TBI severity. Findings support the early vulnerability
      hypothesis and highlight the need for long-term follow-up.

PMID- 28497986
TI  - Traditional Chinese Medicine on the Treatment of Coronary Heart Disease in Recent
      20 Years.
AB  - OBJECTIVE: To analyze the patterns and differences of Chinese herbs in the
      treatment of coronary heart disease (CHD) in different time periods and different
      regions in recent 20 years. DESIGN: The literature of controlled clinical trials
      that focuses on Chinese herbs treating CHD published in China National Knowledge
      Internet and Wanfang database from January 1, 1996 to December 31, 2015 were
      screened to analyze the patterns of herb utilization using SPSS 21.0. RESULTS: A
      total of 1250 articles were enrolled in total covering 29 regions. There were 242
      kinds of single herbs, 18 categories, mentioned a total of 11,594 times. In
      Northeast China, North China, South China, Central China, and Southwest China the
      most frequently used herb was Radix Salviae Miltiorrhizae, but in East China and
      Northwest China, the most frequently used herb was Rhizoma Chuanxiong. The most
      frequently used herb category in North China, Central China, Southwest China, and
      Northwest China was herbs to invigorate blood, but in Northeast China, East
      China, and South China the most frequently used herb category was herbs to
      tonify. CONCLUSION: Single herbs and herb categories to treat CHD in Traditional
      Chinese Medicine differed from time to time and from region to region.

PMID- 28497987
TI  - Elevated Activating Transcription Factor 4 and Glucose-Regulated 78 Kda Protein
      Levels Correlate with Inflammatory Cytokines in the Aqueous Humor and Vitreous of
      Proliferative Diabetic Retinopathy.
AB  - PURPOSE: To determine concentrations of endoplasmic reticulum (ER) stress-related
      factors activating transcription factor 4 (ATF4) and glucose-regulated 78 kDa
      protein (GRP78) in vitreous and aqueous humor (AqH) of patients with
      proliferative diabetic retinopathy (PDR) and the correlation of ATF4, GRP78 and
      inflammatory cytokines interleukin-6(IL-6) and monocyte chemoattractant protein-1
      (MCP-1). MATERIALS AND METHODS: AqH and vitreous samples were collected from eyes
      of patients with PDR and idiopathic macular hole (IMH) which needed vitrectomy.
      Protein Levels of ATF4, GRP78, and IL-6, MCP-1 in samples were evaluated using
      enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA analysis revealed
      significantly increased levels in both AqH and vitreous of ATF4 and GRP78 in eyes
      affected with PDR compared to the controls (all p < 0.001). The mean
      concentrations of IL-6, MCP-1 were also higher in both AqH and vitreous samples
      from patients with PDR compared to those of IMH (all p < 0.001). (Independent
      Student t-test, normality test followed with Skewness-Kurtosis Test). In
      addition, correlations of ATF4 and GRP78 with inflammatory factors IL-6 and MCP-1
      in subjects of patients were analyzed. No significant correlation between the AqH
      concentrations of ATF4/IL-6 and ATF4/MCP-1 was detected in eyes of PDR patients
      (r = 0.346, p = 0.072 and r = 0.275, p = 0.157). Significant correlations were
      observed between AqH concentrations of GRP78/IL-6 (r = 0.724, p < 0.001),
      GRP78/MCP-1 (r = 0.654, p < 0.001) in PDR patients. Significant correlations were
      observed between vitreous concentrations of ATF4/IL-6 (r = 0.918, p < 0.001),
      ATF4/MCP-1 (r = 0.921, p < 0.001), GRP78/IL-6 (r = 0.978, p < 0.001), GRP78/MCP-1
      (r = 0.979, p < 0.001) in PDR patients. No significant correlations was observed
      between AqH concentrations of ATF4/IL-6 (r = 0.187, p = 474), ATF4/MCP-1 (r =
      0.240, p = 0.353), GRP78/IL-6 (r = 0.321, p = 0.209) and GRP78/MCP-1 (r = 0.169,
      p = 0.516) in eyes of IMH patients. And also no significant correlation was
      observed between vitreous concentrations of ATF4/IL-6 (r = 0.130, p = 0.563),
      ATF4/MCP-1(r = 0.029, p = 0.897), GRP78/IL-6 (r = 0.078, p = 0.717), GRP78/MCP-1
      (r = 0.005, p = 0.982) in IMH patients. (Pearson correlation coefficient (two
      tailed)). CONCLUSIONS: Our results demonstrated that ATF4 and GRP78 may play an
      important role in the pathogenesis of PDR and work in concert with inflammatory
      cytokines IL-6 and MCP-1 in pathological process. ATF4 and GRP78 may be good
      diagnostic biomarkers and new therapeutic targets for PDR. ABBREVIATIONS: ER
      stress, endoplasmic reticulum stress; ATF4, activating transcription factor 4;
      GRP78, glucose-regulated 78 kDa protein; AqH, aqueous humor; PDR, proliferative
      diabetic retinopathy; IL-6, interleukin-6; MCP-1, monocyte chemoattractant
      protein-1; IMH, idiopathic macular hole.

PMID- 28497988
TI  - Till Porn Do Us Part? A Longitudinal Examination of Pornography Use and Divorce.
AB  - As pornography use becomes more commonplace in the United States, and
      increasingly so among younger cohorts, a growing literature is considering its
      potential connection to key social and cultural institutions. The current study
      examined the relationship between pornography use and one such institution:
      marriage. We drew on three-wave longitudinal data from 2006 to 2014 General
      Social Survey panel studies to determine whether married Americans' pornography
      use predicted their likelihood of divorce over time and under what social
      conditions. We employed a doubly robust strategy that combines entropy balancing
      with logistic regression models. We found that the probability of divorce roughly
      doubled for married Americans who began pornography use between survey waves (N =
      2,120; odds ratio = 2.19), and that this relationship held for both women and
      men. Conversely, discontinuing pornography use between survey waves was
      associated with a lower probability of divorce, but only for women. Additional
      analyses also showed that the association between beginning pornography use and
      the probability of divorce was particularly strong among younger Americans, those
      who were less religious, and those who reported greater initial marital
      happiness. We conclude by discussing data limitations, considering potential
      intervening mechanisms and the possibility of reverse causation, and outlining
      implications for future research.

PMID- 28497989
TI  - Focus on fluid reasoning: The relationship between fluid reasoning and the
      Pattern of Strengths and Weaknesses model.
AB  - The purpose of this paper is to examine the Fluid Reasoning Index of the Wechsler
      Intelligence Test for Children, Fifth Edition (WISC-V), and determine how fluid
      reasoning skills relate to academic skill acquisition in the classroom setting.
      We also examine the myriad of ways within which learning and learning
      disabilities can be defined. Also, we plan to examine a brief review of the
      definition of a Specific Learning Disability and review some of the leading
      theories related to the Pattern of Strengths and Weaknesses model.

PMID- 28497982
TI  - Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of
      Endocannabinoid System Modulation.
AB  - SIGNIFICANCE: Redox imbalance may lead to overproduction of reactive oxygen and
      nitrogen species (ROS/RNS) and subsequent oxidative tissue damage, which is a
      critical event in the course of neurodegenerative diseases. It is still not fully
      elucidated, however, whether oxidative stress is the primary trigger or a
      consequence in the process of neurodegeneration. Recent Advances: Increasing
      evidence suggests that oxidative stress is involved in the propagation of
      neuronal injury and consequent inflammatory response, which in concert promote
      development of pathological alterations characteristic of most common
      neurodegenerative diseases. CRITICAL ISSUES: Accumulating recent evidence also
      suggests that there is an important interplay between the lipid endocannabinoid
      system [ECS; comprising the main cannabinoid 1 and 2 receptors (CB1 and CB2),
      endocannabinoids, and their synthetic and metabolizing enzymes] and various key
      inflammatory and redox-dependent processes. FUTURE DIRECTIONS: Targeting the ECS
      to modulate redox state-dependent cell death and to decrease consequent or
      preceding inflammatory response holds therapeutic potential in a multitude of
      oxidative stress-related acute or chronic neurodegenerative disorders from stroke
      and traumatic brain injury to Alzheimer's and Parkinson's diseases and multiple
      sclerosis, just to name a few, which will be discussed in this overview.
      Antioxid. Redox Signal. 29, 75-108.

PMID- 28497990
TI  - Parental Mediation Regarding Children's Smartphone Use: Role of Protection
      Motivation and Parenting Style.
AB  - Parental mediation is a type of behavior that could protect children against the
      negative uses and effects of smartphones. Based on protection motivation theory,
      this research (a) predicted parental mediation based on parents' threat and
      efficacy perceptions and (b) predicted threat and efficacy perceptions based on
      parenting styles and parents' addiction to smartphone use. An online survey of
      448 parents of fourth to sixth graders was conducted. Results showed that both
      restrictive and active parental mediation were predicted by perceived severity,
      response efficacy, and self-efficacy. With regard to parenting styles, (a)
      authoritative parenting was positively related to perceived severity as well as
      response- and self-efficacy, whereas (b) permissive parenting was negatively
      related to self-efficacy. In addition, parents' addiction was a negative
      predictor of perceived severity, but a positive predictor of perceived
      susceptibility.

PMID- 28497991
TI  - Medical Students' Professional Development as Educators Revealed Through
      Reflections on Their Teaching Following a Students-as-Teachers Course.
AB  - : Phenomenon: Teaching is an important part of the tri-partite mission of every
      medical center. Although teaching often is given lower priority and recognition
      as opposed to patient care and/or research, this activity for many physicians in
      academic medicine ranks second to their patient care responsibilities. Medical
      teacher training has traditionally been aimed at faculty and residents through
      faculty development initiatives, continuing education for physicians at
      professional conferences, formalized degree or certificate programs in education,
      and residents as teachers programs. More recently medical schools have developed
      medical-students-as-teachers programs, often offered as 4th-year electives, to
      introduce learners to the theory of teaching and learning with appropriate
      application in the clinical setting. Data on learner outcomes and students'
      perceptions and experiences in these programs consist mostly of their
      satisfaction after completing such a program. In this article we explore 4th-year
      medical student trainees' experiences and emerging self-concepts as educators
      during a teaching elective. APPROACH: The purpose of this project was to explore
      students' reflections on their experiences in a 4th-year medical students-as
      teachers course in their own words through their written self-assessment
      narratives. We used qualitative content analysis to examine 96 trainees' self
      reported, written reflective narratives of how they translated their students-as
      teachers course experience into application by applying newly learned educational
      theories, instructional strategies, and feedback skills while teaching novice
      peers physical diagnosis skills. FINDINGS: Narratives revealed candid self
      assessments and detailed descriptions of their experiences and what they valued
      most from the course. Content analysis revealed nine key themes: using teaching
      strategies for adult learning, preparing for class, modeling professionalism,
      incorporating clinical correlations, exceeding course requirements, giving and
      receiving feedback, providing mentoring, creating a positive learning climate,
      and growing as educators. Insights: This study's results reveal how learners
      perceive and translate their experiences in a teaching course, in terms of
      incorporating particular knowledge or skills, valuing or displaying certain
      professional behaviors, and gaining self-awareness and satisfaction from teaching
      experiences. The findings of this study, specifically major themes from self
      assessment narratives, provide us with a better understanding of medical
      students' developing identities and emerging professional self-concept as
      educators, specifically as experienced through a combination of formal teaching,
      and applying education theories and strategies. Findings may be informative from
      a program evaluation lens but also for faculty development initiatives related to
      training medical teachers and the larger landscape of the emerging field of
      Health Professions Education.

PMID- 28497992
TI  - How does anxiety influence fluid reasoning?
AB  - Does anxiety influence fluid reasoning, either negatively or positively? The
      purpose of this article was to review much of the relevant current literature to
      answer this question. An individual's ability to employ fluid reasoning to solve
      novel problems must include the context of the circumstances, the individual's
      unique set of cognitive resources, one's ability to utilize previously acquired
      knowledge from similar situations, and to create a solution in a quick and
      effective manner. Working memory and creativity are cognitive skill sets that
      influence the efficiency and effectiveness of novel problem solving, while
      anxiety can be a crippling factor for some. This article aims to discuss the role
      of each of these factors the implementation of novel problem solving with a
      special emphasis on the role of development during adolescence.

PMID- 28497994
TI  - Temperamental Effortful Control Modulates Gender Differences in Late Positive
      Potentials Evoked by Affective Pictures in Adolescents.
AB  - We investigated whether effort control (EC) modulates gender differences in late
      positive potential (LPP) evoked by affective pictures. We collected EEG data from
      46 healthy adolescents while they viewed 90 affective pictures. Relative to
      neutral pictures, boys showed larger LPP amplitudes for positive pictures
      compared to girls while girls showed larger LPP amplitudes for negative pictures
      compared to boys. Temperamental EC in boys negatively predicted LPP amplitudes
      for positive pictures, whereas EC in girls negatively predicted LPP amplitudes
      for negative pictures. These observations increase our understanding of the
      relationship between EC and gender difference in electrocortical maturation.

PMID- 28497993
TI  - Personal Variation in Preference for Sweetness: Effects of Age and Obesity.
AB  - BACKGROUND: Use of nonnutritive sweeteners (NNSs), which provide sweet taste with
      few to no calories, has increased, but data on whether children's hedonic
      responses to NNSs differ from nutritive sugars or from adults' hedonic responses
      are limited. METHODS: Most preferred levels of sucrose and the NNS sucralose were
      determined via a forced-choice tracking procedure in 48 children, 7-14 years
      (mean = 10 years), and 34 adults. Each participant also rated the liking of these
      taste stimuli, as well as varying concentrations of aspartame on 3- and 5-point
      facial hedonic scales. Anthropometric measures were obtained, and motives for
      palatable food intake were assessed with the Palatable Eating Motives Scale
      (PEMS, adults) and Kids PEMS. RESULTS: While use of the 3-point scale showed no
      age-related differences in liking of sweeteners, the 5-point scale showed that
      more children than adults liked higher concentrations of sucrose, sucralose, and
      aspartame, and the tracking procedure showed that children most preferred higher
      concentrations of sucrose and sucralose than adults. Regardless of age, sweet
      preference did not differ between obese and nonobese participants and showed no
      association with motives for eating palatable foods. Children's body mass index z
      scores were positively associated with social and conformity motive scores for
      eating palatable foods. CONCLUSION: Research should move beyond measures of
      variation in sweet taste hedonics to include identifying motives, and the
      physiological and psychological consequences of eating sweets, to shed light on
      what children are more vulnerable to develop unfavorable eating habits,
      increasing risk for obesity, and other diseases.

PMID- 28497995
TI  - A rare case of small cell carcinoma of lung with intraventricular metastasis.
AB  - Our case report involves a Chinese patient who was presented to our hospital with
      the chief complaint of dizziness and double vision for one week. He was diagnosed
      with small cell carcinoma of lung in the past. The patient undertook various test
      at our hospital. His MR scan revealed an intraventricular metastasis from small
      cell carcinoma of lung which is very rare. We have analyzed the clinical data of
      this patient and related literature. We report this case to increase the
      awareness of this rare metastasis of small cell carcinoma of lung.

PMID- 28497996
TI  - Characterization of the Salmonella enterica Serotype Isangi Isolated from
      Patients for the First Time in China.
AB  - No studies have reported the isolation of serotype Salmonella Isangi from cases
      of salmonellosis in mainland China. We investigated an outbreak of foodborne
      disease with salmonella and collected the samples from the patients and surplus
      foods. Salmonella strains were isolated and the serotype was identified according
      to the Kauffmann-White scheme. The relatedness of the isolates was determined
      using pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS).
      Antimicrobial susceptibility was conducted by the broth microdilution method.
      There were 74 diners in the case, 33 of which got ill, with an attack rate of
      44.6% (33/74). A total of 24 samples were collected from the outbreak cases, six
      Salmonella Isangi strains were isolated and susceptible to all tested drugs. PFGE
      and WGS analysis suggested that the pathogen dissemination through a single or
      limited vector(s), the steamed fish and mixed food (fry spicy chicken, braised
      pork ribs, and goose leg), may be the source of infection or be cross
      contaminated. We first report the characteristics of an outbreak and molecular
      strain relatedness of Salmonella Isangi in mainland China.

PMID- 28497997
TI  - Homophily in an Anonymous Online Community: Sociodemographic Versus Personality
      Traits.
AB  - In what traits do people interact with others who are similar to them in
      completely anonymous online communication? Can those traits contribute to greater
      exchange of opinion and information across the sociodemographic boundaries that
      often limit interaction between social strata? To answer this question concerning
      online homophily, we combined survey data on 7,287 users (aged 18 and above) of a
      Korean online dating advice platform with their behavioral data from June 2015 to
      August 2015 and explored whether advice exchange occurred between users with
      similar sociodemographic and personality traits. On this platform, two types of
      interactions occurred as follows: (1) responses to a randomly distributed problem
      submitted by an advice seeker and (2) the seeker's indication of approval of any
      of the responses given. The study found that (1) a receiver was more likely to
      respond to problems submitted by seekers of a comparable age and that (2) seekers
      were more likely to approve of a response if the seeker and receiver had similar
      educational backgrounds. By contrast, homophily based on personality traits was
      not observed even though some personality traits significantly affected the
      likelihood of both response and approval. Our findings suggest that online
      communication may breed sociodemographic homophily, whether based on age or
      education, more than expected or intended while not easily fostering alternative
      forms of homophily, such as personality homophily, which can potentially cut
      across borders dividing sociodemographic groups.

PMID- 28497999
TI  - Bullet fragment fiducials in stereotactic body radiotherapy as a bridge to
      transplant for hepatocellular carcinoma.

PMID- 28498000
TI  - Metastatic brain carotid body paraganglioma with endocrine activity: a case
      report and literature review.
AB  - A woman with hypertension and hyperglycemia was diagnosed a metastatic brain
      carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were
      normal after craniotomy. Although most carotid body tumors are benign, a few show
      distant metastasis. This is the first reported case of intracerebral metastases
      from a carotid body tumor.

PMID- 28497998
TI  - Transcriptional reprogramming in cellular quiescence.
AB  - Most cells in nature are not actively dividing, yet are able to return to the
      cell cycle given the appropriate environmental signals. There is now ample
      evidence that quiescent G0 cells are not shut-down but still metabolically and
      transcriptionally active. Quiescent cells must maintain a basal transcriptional
      capacity to maintain transcripts and proteins necessary for survival. This
      implies a tight control over RNA polymerases: RNA pol II for mRNA transcription
      during G0, but especially RNA pol I and RNA pol III to maintain an appropriate
      level of structural RNAs, raising the possibility that specific transcriptional
      control mechanisms evolved in quiescent cells. In accordance with this, we
      recently discovered that RNA interference is necessary to control RNA polymerase
      I transcription during G0. While this mini-review focuses on yeast model
      organisms (Saccharomyces cerevisiae and Schizosaccharomyces pombe), parallels are
      drawn to other eukaryotes and mammalian systems, in particular stem cells.

PMID- 28498001
TI  - ABCE1: A special factor that orchestrates translation at the crossroad between
      recycling and initiation.
AB  - For many years initiation and termination of mRNA translation have been studied
      separately. However, a direct link between these 2 isolated stages has been
      suggested by the fact that some initiation factors also control termination and
      can even promote ribosome recycling; i.e. the last stage where post-terminating
      80S ribosomes are split to start a new round of initiation. Notably, it is now
      firmly established that, among other factors, ribosomal recycling critically
      requires the NTPase ABCE1. However, several earlier reports have proposed that
      ABCE1 also somehow participates in the initiation complex assembly. Based on an
      extended analysis of our recently published late-stage 48S initiation complex
      from rabbit, here we provide new mechanistic insights into this putative role of
      ABCE1 in initiation. This point of view represents the first structural evidence
      in which the regulatory role of the recycling factor ABCE1 in initiation is
      discussed and establishes a corner stone for elucidating the interplay between
      ABCE1 and several initiation factors during the transit from ribosomal recycling
      to formation of the elongation competent 80S initiation complex.

PMID- 28498002
TI  - An observation study of the clinical evaluation of symptom relief and side
      effects associated with taking ulipristal acetate (esmya) including its effect on
      pre-menstrual syndrome.
AB  - This was an observational study investigating the efficacy and side effects
      associated with ulipristal acetate (UPA), a progesterone receptor modulator, and
      the possible benefits to women who have co-existing pre-menstrual syndrome (PMS).
      80 women returned a questionnaire on the bleeding, menstrual pain and side
      effects, and changes on PMS were recorded. 67 women (84%) showed improvement in
      their menses. 54 women (67%) became amenorrhoeic. Of those, 67% were within 10
      days of commencing UPA. Menses returned in 33 amenorrhoeic women within 4 weeks
      of stopping UPA. 58 women (70%) reported an improvement in their pain score but
      41 women had a return of their pain after stopping UPA. The majority of the women
      had no or infrequent side effects. 80% had demonstrable improvement in their PMS
      symptoms. UPA is effective in controlling symptoms due to uterine fibroids with
      infrequent side effects. Our data also showed new evidence of a concurrent
      dramatic improvement in PMS in these women. Impact statement The observational
      study explored the drug profile of ulipristal acetate (UPA), a selective
      progesterone receptor modulator, which has been licenced as pre-treatment for
      surgical therapies of fibroids since 2012. We aimed to investigate the efficiency
      and side effects of UPA. Since the introduction of UPA in clinical practice,
      there has yet to be a study looking at the drug profile outside a research
      setting. We have also decided to investigate the effect of UPA on pre-menstrual
      syndrome (PMS) in this group of women with symptomatic fibroids. As such this
      case report should be of interest to a broad readership including those
      interested in the medical management of symptomatic fibroids.

PMID- 28498003
TI  - A Novel Approach to Assessing Professionalism in Preclinical Medical Students
      Using Multisource Feedback Through Paired Self- and Peer Evaluations.
AB  - : Phenomenon: Professionalism is integral to the role of the physician. Most
      professionalism assessments in medical training are delayed until clinical
      rotations where multisource feedback is available. This leaves a gap in student
      assessment portfolios and potentially delays professional development. APPROACH:
      A total of 246 second-year medical students (2013-2015) completed self- and peer
      assessments of professional behaviors in 2 courses following a series of Team
      Based Learning exercises. Correlation and regression analyses were used to
      examine the alignment or misalignment in the relationship between the 2 types of
      assessments. Four subgroups were formed based on observed patterns of initial
      self- and peer assessment alignment or misalignment, and subgroup membership
      stability over time was assessed. A missing data analysis examined differences
      between average peer assessment scores as a function of selective
      nonparticipation. FINDINGS: Spearman correlation demonstrated moderate to strong
      correlation between self-assessments completed alone (no simultaneous peer
      assessment) and self-assessments completed at the time of peer assessments (rho =
      .59, p < .0001) but weak correlation between the two self-assessments and peer
      assessments (alone: rho = .13, p < .013; at time of peer: rho = .21, p < .0001).
      Generalized estimating equation models revealed that self-assessments done alone
      (p < .0001) were a significant predictor of self-assessments done at the time of
      peer. Course was also a significant predictor (p = .01) of self-assessment scores
      done at the time of peer. Peer assessment score was not a significant predictor.
      Bhapkar's test revealed subgroup membership based on the relationship between
      self- and peer ratings was relatively stable across Time 1 and Time 2 assessments
      (chi2 = 0.83, p = .84) for all but one subgroup; members of the subgroup with
      initially high self-assessment and low peer assessment were significantly more
      likely to move to a new classification at the second measurement. A missing data
      analysis revealed that students who completed all self-assessments had
      significantly higher average peer assessment ratings compared to students who
      completed one or no self-assessments with a difference of -0.32, 95% confidence
      interval [-0.48, -0.15]. Insights: Multiple measurements of simultaneous self-
      and peer assessment identified a subgroup of students who consistently rated
      themselves higher on professionalism attributes relative to the low ratings given
      by their peers. This subgroup of preclinical students, along with those who
      elected to not complete self-assessments, may be at risk for professionalism
      concerns. Use of this multisource feedback tool to measure perceptual stability
      of professionalism behaviors is a new approach that may assist with early
      identification of at-risk students during preclinical years.

PMID- 28498004
TI  - A Sequential Implementation Model for Workforce Development: A Case Study of
      Medical Residency Training for Substance Use Concerns.
AB  - PROBLEM: In graduate medical education, residency programs are often
      educationally isolated from each other, with varying needs and patient
      populations, so strategies are needed when attempting to implement training in
      evidence-based practices across multiple residencies. INTERVENTION: Using
      implementation science as a guide, we adapted a community development model to
      sequentially implement an evidence-based intervention, Screening, Brief
      Intervention, and Referral to Treatment (SBIRT) for alcohol and drug use
      problems, across internal medicine, pediatrics, emergency medicine, psychiatry,
      and obstetrics and gynecology residency programs. CONTEXT: A grant-funded
      "executive" team coordinated the implementation, enrolled a new residency program
      annually, and served as the consultative team to span the programs. The team was
      attentive to aligning implementation with the needs of each program. To assist in
      planning, the team included a program champion 1 year prior to SBIRT
      implementation to provide the opportunity to develop resources and work with
      peers. We evaluated this model through an implementation science lens using a
      case study approach that included interviews and quantitative tabulation of
      products and resident perceptions. OUTCOME: We successfully instituted SBIRT
      training in all 5 residency programs through the use of a supported local
      champion model. Teams developed 90 curricular products and had 57 presentations
      and publications. Residents reported satisfaction with the SBIRT activities.
      Champions reported that SBIRT was a useful approach and that they gained valuable
      knowledge and relationships from working with the executive team when designing
      learning materials appropriate for their residency. Champions successfully
      incorporated SBIRT into routine clinical practice. LESSONS LEARNED: Having a
      strong team to support subsequent SBIRT champions was essential for
      implementation. The champions needed financial support to have the necessary time
      to implement training. The strategy of building a peer network across programs
      was critical for sustaining the implementation. Collecting and sharing resources
      aided the champions in developing their materials.

PMID- 28498005
TI  - School Protective Factors and Substance Use Among Lesbian, Gay, and Bisexual
      Adolescents in California Public Schools.
AB  - PURPOSE: The majority of studies examining substance use among lesbian, gay, and
      bisexual (LGB) youth have focused on a wide array of risk factors (e.g.,
      victimization). Few studies have explored the protective role of schools. This
      study aims to fill this gap in the literature and inform programs aimed at
      reducing substance use among LGB youth. More specifically, this study explores
      the extent to which school connectedness and support from teachers and other
      adults at school are associated with substance use among LGB youth in school and
      within the past 30 days. METHODS: A secondary analysis of the 2013-2015
      California Healthy Kids Survey (CHKS) was conducted to examine associations
      between school protective factors (i.e., school connectedness and adult support)
      and substance use among LGB youth, above and beyond a key risk factor, school
      victimization. The study outcomes were past 30-day and in-school use of
      cigarettes, alcohol, marijuana, inhalants, prescription pain medication, and
      other illegal drugs. RESULTS: Overall, school connectedness and school adult
      support were associated with lower odds of substance use. For example, higher
      levels of school connectedness were associated with 22% decreased odds of past 30
      day inhalant use (adjusted odds ratio [AOR] = 0.78; 95% confidence interval [CI]
      = 0.72-0.86), and 25% decreased odds of past 30-day prescription pain medication
      use (AOR = 0.75; 95% CI = 0.69-0.82). Higher levels of adult support in school
      were also associated with 17% decreased odds of marijuana use on school property
      in the past 30 days (AOR = 0.83; 95% CI = 0.77-0.91). CONCLUSION: The results
      indicate a need for substance use prevention programs that integrate school
      connectedness and adult support in school.

PMID- 28498006
TI  - Serum YKL-40 as a potential biomarker of inflammation in psoriasis.
AB  - OBJECTIVE: YKL-40 is an inflammatory glycoprotein associated with
      atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are
      common comorbidities in psoriasis. The aim of the study was to assess serum YKL
      40 level in psoriasis and elucidate possible associations with disease activity,
      inflammatory or metabolic parameters and treatment. METHODS: A total of 37
      individuals with active plaque-type psoriasis and 15 healthy controls were
      enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum
      YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay
      (ELISA). The results were correlated with Psoriasis Area and Severity Index
      (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid
      profile and topical therapy. RESULTS: Median YKL-40 serum levels were
      significantly increased in psoriatic patients in comparison to the controls (p <
      .0001). No significant correlations between investigated protein and metabolic
      parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found.
      Significant positive relation with CRP (p = .003) or alanine aminotransferase (p
      = .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level
      remained unchanged (p = .5) after topical treatment, despite clinical
      improvement. CONCLUSIONS: YKL-40 might be a biomarker of psoriasis and
      inflammation in psoriatic patients, but not a reliable indicator of metabolic
      conditions, severity of psoriasis nor efficacy of the treatment.

PMID- 28498007
TI  - Are Hybrid Liver Resections Truly Minimally Invasive? A Propensity Score Matching
      Analysis.
AB  - BACKGROUND: Hybrid liver resection is considered a modality of minimally invasive
      surgery; however, there are doubts regarding loss of benefits of laparoscopy due
      to the use of an auxiliary incision. We compared perioperative results of
      patients undergoing hybrid * open and hybrid * pure laparoscopic resections.
      METHODS: Consecutive patients undergoing liver resection between June 2008 and
      January 2016 were studied. Study groups were compared after propensity score
      matching (PSM). RESULTS: Six hundred forty-four resections were included in the
      comparative analysis: 470 open, 120 pure laparoscopic, and 54 hybrids. After PSM,
      54 patients were included in each group. Hybrid * open: hybrid technique had
      shorter operative time (319.5 +/- 108.6 * 376.2 +/- 155.8 minutes, P = .033),
      shorter hospital stay (6.0 +/- 2.7 * 8.1 +/- 5.6 days, P = .001), and lower
      morbidity (18.5% * 40.7%, P = .003). Hybrid * pure laparoscopic: hybrid group had
      lower conversion rate (0% * 13%, P = .013). There was no difference regarding
      estimated blood loss, transfusion rate, hospital stay, complications, or
      mortality. CONCLUSIONS: Hybrid resection has better perioperative results than
      the open approach and is similar to pure laparoscopy. The hybrid technique should
      be considered a minimally invasive approach.

PMID- 28498008
TI  - Spatial Orientation and Navigation in Children With Perinatal Stroke.
AB  - As a focal injury in an otherwise healthy child, perinatal stroke provides a
      clinical model of developmental brain plasticity. In this study, we report
      evidence that children with perinatal periventricular venous infarcts perform as
      well as control children on a video game that tests navigation abilities. In
      addition, children with a history of perinatal arterial strokes overcame initial
      deficits in navigation performance after additional practice. These findings lend
      support to the hypothesis that a complex cognitive skill dependent on a
      distributed neural network with prolonged maturation, such as navigation, may
      demonstrate resilience after early brain injury.

PMID- 28498009
TI  - 'I feel better when...': An analysis of the memory-experience gap for peoples'
      estimates of the relationship between health behaviours and experiences.
AB  - OBJECTIVE: People often overestimate how strongly behaviours and experiences are
      related. This memory-experience gap might have important implications for health
      care settings, which often require people to estimate associations, such as "my
      mood is better when I exercise". This study examines how subjective correlation
      estimates between health behaviours and experiences relate to calculated
      correlations from online reports and whether subjective estimates are associated
      with engagement in actual health behaviour. DESIGN: Seven-month online study on
      physical activity, sleep, affect and stress, with 61 online assessments. MAIN
      OUTCOME MEASURES: University students (N = 168) retrospectively estimated
      correlations between physical activity, sleep, positive affect and stress over
      the seven-month study period. RESULTS: Correlations between experiences and
      behaviours (online data) were small (r = -.12-.14), estimated correlations
      moderate (r = -.35-.24). Correspondence between calculated and estimated
      correlations was low. Importantly, estimated correlations of physical activity
      with stress, positive affect and sleep were associated with actual engagement in
      physical activity. CONCLUSION: Estimation accuracy of relations between health
      behaviours and experiences is low. However, association estimates could be an
      important predictor of actual health behaviours. This study identifies and
      quantifies estimation inaccuracies in health behaviours and points towards
      potential systematic biases in health settings, which might seriously impair
      intervention efficacy.

PMID- 28498010
TI  - From play to problem solving to Common Core: The development of fluid reasoning.
AB  - How and when does fluid reasoning develop and what does it look like at different
      ages, from a neurodevelopmental and functional perspective? The goal of this
      article is to discuss the development of fluid reasoning from a practical
      perspective of our children's lives: from play to problem solving to Common Core
      Curriculum. A review of relevant and current literature supports a connection
      between movement, including movement through free play, and the development of
      novel problem solving. As our children grow and develop, motor routines can
      become cognitive routines and can be evidenced not only in games, such as chess,
      but also in the acquisition and demonstration of academic skills. Finally, this
      article describes the connection between novel problem solving and the demands of
      the Common Core Curriculum.

PMID- 28498011
TI  - Factors Associated with Antiretroviral Therapy Adherence Among Transgender Women
      Receiving HIV Medical Care in the United States.
AB  - PURPOSE: We examined factors associated with antiretroviral therapy (ART)
      adherence among transgender women living with HIV (TWLWH). METHODS: We used
      combined data from the 2009 to 2013 cycles of Medical Monitoring Project, an HIV
      surveillance system designed to produce nationally representative estimates of
      the characteristics of HIV-infected adults receiving HIV medical care in the
      United States. Rao-Scott chi-square tests and multivariable logistic regression
      were used to identify factors associated with dose adherence (defined as taking
      100% of prescribed ART doses in the past 3 days). RESULTS: Among TWLWH who
      reported current ART use, an estimated 80.5% self-reported dose adherence.
      Multivariable factors independently associated with lower (<100%) dose adherence
      were younger age (30-39 vs. 40 and over), not having health insurance coverage,
      depression, lower self-efficacy to take medication as prescribed, and having
      greater than one daily ART dose. CONCLUSION: Our findings suggest several ways to
      potentially improve ART adherence of TWLWH including tailoring efforts to address
      the needs of TWLWH under age 40, increasing access to health insurance coverage,
      addressing mental health morbidities, building skills to improve medication
      adherence self-efficacy, and simplifying ART regimens when possible.

PMID- 28498012
TI  - Unmet expectations of medications and care providers among patients with heart
      failure assessed to be poorly adherent: results from the Chronic Heart Failure
      Intervention to Improve MEdication Adherence (CHIME) study.
AB  - BACKGROUND: Ineffective medication management contributes to repeated
      hospitalisation and death among patients with heart failure. The meaning ascribed
      to medications and the influence of meaning on how patients manage medications is
      unknown. The purpose of this study was to explore the meaning and expectations
      associated with medication use in high-risk, non-adherent patients with heart
      failure. METHODS AND RESULTS: Patients ( n=265) with heart failure were screened
      for adherence to prescribed medication using the Morisky medication adherence
      scale (MMAS). Patients (MMAS score <6; n=44) participated in semistructured
      interviews, analysed using qualitative content analysis. Of 17 initial themes
      (223 representative segments), the overarching theme 'unmet expectations'
      consisted of two subthemes 'working to be heard' by professionals and
      'resignation' to both the illness and medications. Patients' expectations were
      challenged by unexpected work to communicate with providers in general (72
      representative segments), and specifically regarding medications (118
      representative segments) and feelings of resignation regarding the medication
      regimen (33 representative segments). CONCLUSIONS: These findings suggest that
      unmet expectations contribute to poor medication management. Improved listening
      and communication by providers, to establish a common understanding and plan for
      managing medications may strengthen patient beliefs, resolve feelings of
      resignation and improve patients' ability to manage medications effectively.

PMID- 28498014
TI  - Self-efficacy as a predictor of treatment outcome in an outpatient eating
      disorder program.
AB  - This prospective pilot study examined the relationship between self-efficacy and
      treatment outcome in an adult outpatient eating disorder program. Data from 59
      eating disorder outpatients were collected, including measures of self-efficacy,
      eating disorder symptom severity, negative emotions (depression, anxiety, and
      stress), body mass index, and duration of illness. Hierarchical regression was
      used to examine the impact of baseline self-efficacy, and early treatment changes
      in self-efficacy (i.e., baseline to 6 weeks), on end-of-treatment (EoT) eating
      disorder symptom severity and treatment dropout. Early change in self-efficacy
      during the course of treatment was found to predict EoT symptom severity when
      controlling for confounding variables. Furthermore, baseline self-efficacy was
      found to predict treatment dropout, but not end-of-treatment symptom severity.
      This is the first study (using a validated scale) to show that self-efficacy, and
      early changes in self-efficacy, may be an important predictor of treatment
      outcome for eating disorder outpatients. Implications and suggestions for future
      research are discussed.

PMID- 28498013
TI  - Disparities in Counseling Female Cancer Patients for Fertility Preservation.
AB  - BACKGROUND: Female cancer patients who are exposed to gonadotoxic chemotherapy
      are at risk of future infertility. Research suggests that disparities in
      fertility preservation counseling (FPC) may exist. Previous research is limited
      by recall bias; therefore, this study examined objective electronic medical chart
      data regarding FPC at an academic medical center. MATERIALS AND METHODS: This
      study included reproductive-aged women (18-45 years old) with a diagnosis of
      breast, gynecological, or hematological cancer and who were exposed to a
      gonadotoxic chemotherapeutic agent from 2009 to 2013. Chi-square and logistic
      regression analyses were utilized to analyze disparities in FPC. RESULTS: Two
      hundred fifty-nine women met the study criteria. One hundred eighty-one women
      were diagnosed with breast cancer, 52 with hematological cancer, and 26 with
      gynecological cancer. 160/259 (62%) women had documented counseling for fertility
      preservation (FP), 60 (23%) women were not counseled as counseling was determined
      to be "not applicable," 16 (6%) women were not counseled and no explanation was
      given for the lack of counseling, and counseling was not documented in 23 (9%)
      charts. Age, marital status, and racial/ethnic background were related to
      counseling status. Patients with gynecological or hematological cancer were more
      likely to be counseled than other patients. Logistic regression results
      demonstrated that FPC was largely driven by cancer diagnosis. CONCLUSIONS:
      Although cancer diagnosis was the greatest predictor of FPC, disparities were
      evident in the counseling of female cancer patients for FP treatment. Equality in
      counseling female patients for FP treatment is imperative to reduce the risk of
      emotional harm and future infertility.

PMID- 28498015
TI  - Tracking the Functional Development of the Corpus Callosum in Children Using
      Behavioral and Evoked Potential Interhemispheric Transfer Times.
AB  - Visual functions requiring interhemispheric transfer exhibit a long developmental
      trajectory up to age 12, which might be constrained by corpus callosum
      maturation. Here, we use electrophysiological and behavioral crossed-uncrossed
      differences (CUDs) in a visual Poffenberger paradigm to estimate the
      interhemispheric transfer time (IHTT)-a measure of corpus callosum maturation-in
      7-year-old children and adults. Adults' electrophysiological CUDs were faster
      than 7-year-olds'. Behavioral CUDs did not differ and proved to be unreliable in
      a 6-month follow-up test. These findings suggest that the corpus callosum still
      undergoes development at the age of 7 that can only reliably be traced with
      neuroscientific methods.

PMID- 28498016
TI  - Accelerated vernalization response by an altered PHD-finger protein in
      Arabidopsis.
AB  - Vernalization is a response to the winter cold to acquire the competence to
      flower in next spring. VERNALIZATION INSENSITIVE 3 (VIN3) is a PHD-finger protein
      that binds to modified histones in vitro. VIN3 is induced by long-term cold and
      is necessary for Polycomb Repression Complex 2 (PRC2)-mediated tri-methylation of
      Histone H3 Lysine 27 (H3K27me3) at the FLC locus in Arabidopsis. An alteration in
      the PHD-finger domain of VIN3 changes the binding specificity of the PHD-finger
      domain of VIN3 in vitro and results in an accelerated vernalization response in
      vivo. The acceleration in vernalization response is achieved by increased
      enrichments of VIN3 and tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the
      FLC locus without invoking the increased enrichment of Polycomb Repressive
      Complex 2. This result indicates that the binding specificity of the PHD-finger
      domain of VIN3 plays a role in mediating a proper vernalization response in
      Arabidopsis. Furthermore, this work shows a potential that the alteration of PHD
      finger domains could be applied to alter various developmental processes in
      plants.

PMID- 28498017
TI  - Dietary Supplements as Surrogate of Mediterranean Diet in Healthy Smoking
      Subjects.
AB  - The interventions to slow aging, favoring active life expectancy, represent the
      new perspectives in ageing investigation. Some mechanisms that delay or prevent
      the onset of aging pathologies have been identified. Between them, a healthy
      lifestyle seems to reduce many risk factors. In particular, eating habits
      represent the most concrete, low-cost way to act on aging process. Mediterranean
      diet has received much attention since its antioxidant and anti-inflammatory
      effects have been consistently demonstrated. Unfortunately, many people follow a
      Western diet, poor in phytochemicals that represent the main source of beneficial
      effects of this dietary pattern. So, supplements administration should be
      considered, especially in subjects exposed to high level of oxidative stress and
      inflammation. So, we tested the properties of a commercial food supplement
      containing a series of plant polyphenols in combination with caffeine, bioperine
      (black pepper extract), and selenium in smoking healthy volunteers. Fifty
      participants have been recruited and hematochemical analyses and biochemistry
      tests have been performed, before and after 60 days of supplement intake.
      Thirteen subjects dropped out of the study. At the end of the intervention, the
      variation of inflammatory and oxidant markers has been evaluated, measuring
      urinary isoprostanes, serum advanced glycation end products, and oxidized low
      density lipoproteins. The results showed that this supplement exhibits promising
      antioxidant and anti-inflammatory responses, especially in women, highlighting
      the role of supplementation in certain groups of subjects, for the control of
      oxidative stress as well as inflammatory status. So, its intake should be useful
      in delaying the onset of age-related diseases.

PMID- 28498018
TI  - Full Robotic Colorectal Resections for Cancer Combined With Other Major Surgical
      Procedures: Early Experience With the da Vinci Xi.
AB  - BACKGROUND: The da Vinci Xi has been developed to overcome some of the
      limitations of the previous platform, thereby increasing the acceptance of its
      use in robotic multiorgan surgery. METHODS: Between January 2015 and October
      2015, 10 patients with synchronous tumors of the colorectum and others abdominal
      organs underwent robotic combined resections with the da Vinci Xi. Trocar
      positions respected the Universal Port Placement Guidelines provided by Intuitive
      Surgical for "left lower quadrant," with trocars centered on the umbilical area,
      or shifted 2 to 3 cm to the right or to the left, depending on the type of
      combined surgical procedure. RESULTS: All procedures were completed with the full
      robotic technique. Simultaneous procedures in same quadrant or left quadrant and
      pelvis, or left/right and upper, were performed with a single docking/single
      targeting approach; in cases of left/right quadrant or right quadrant/pelvis, we
      performed a dual-targeting operation. No external collisions or problems related
      to trocar positions were noted. No patient experienced postoperative surgical
      complications and the mean hospital stay was 6 days. CONCLUSIONS: The high
      success rate of full robotic colorectal resection combined with other surgical
      interventions for synchronous tumors, suggest the efficacy of the da Vinci Xi in
      this setting.

PMID- 28498019
TI  - Severe human parechovirus type 3 infection in adults associated with
      gastroenteritis in their children.

PMID- 28498021
TI  - Successful treatment of Becker's Nevus with long-pulsed 1064-nm Nd:YAG and 755-nm
      alexandrite laser and review of the literature.
AB  - BACKGROUND: Becker's Nevus is an aesthetically troublesome condition secondary to
      hyperpigmentation and hypertrichosis. Although several lasers have been employed
      with varying degrees of success, the exact devices and treatment parameters have
      yet to be elucidated. OBJECTIVE: To assess the combination Nd:YAG and alexandrite
      laser as a safe and efficacious treatment for Becker's Nevus. METHODS: In a 20
      year-old Fitzpatrick Skin Type IV male, a Becker's Nevus was treated with six
      sessions of long-pulsed 1064 nm Nd:YAG laser at six-week intervals followed by
      five sessions of long-pulsed 755 nm alexandrite laser at three-month intervals.
      RESULTS: This patient experienced a significant reduction in both
      hyperpigmentation and hypertrichosis after these treatment sessions. No serious
      adverse events were reported. CONCLUSION: This case supports the use of
      combination long-pulsed 1064 nm laser and 755 nm laser as a safe and efficacious
      treatment for Becker's Nevus.

PMID- 28498020
TI  - Cell cycle genes are activated earlier than respiratory genes during release of
      grapevine buds from endodormancy.
AB  - Single-bud cuttings of Vitis vinifera L exposed to forced growing conditions were
      used to investigate the involvement of phytohormones, abscisic acid (ABA), auxin
      (Aux) and cytokinin (CK) in the release of buds from the ED and in bud-sprouting.
      This artificial system imitates and hastens the natural sprouting that occurs in
      spring. Temporal expression analysis of genes related to phytohormones synthesis,
      showed an early drop in the expression of ABA biosynthesis gene that preceded an
      increase in Aux and CK biosynthesis genes. Bud-break is headed by the activation
      of all structures of the latent bud, especially the differentiation of the
      inflorescence and the development of the early stages of floral organs.
      Therefore, resumption of cell division and increases in respiration are essential
      for the activation of the bud. Temporal expression analysis of the cell cycle and
      respiration genes indicate that an increase in cell division go before the
      increase in respiration. These results, together with results indicating that the
      cell cycle genes are upregulated by Aux and CK, suggest that the events before
      the bud-break, start with a reduction in ABA content, followed by an increase in
      the content of Aux and CK, which activates the machinery of the cell cycle, which
      eventually would cause an increase in respiration.

PMID- 28498022
TI  - Thyroid hormone analogs for the treatment of dyslipidemia: past, present, and
      future.
AB  - OBJECTIVE: Treatment of dyslipidemia is a major burden for public health. Thyroid
      hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR),
      but the use of thyroid hormone to treat dyslipidemia is not indicated due to its
      deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been
      conceived to selectively activate TR in the liver, thus reducing potential side
      effects. METHODS: The authors searched the PubMed database to review TR and the
      action of thyromimetics in vitro and in animal models. Then, all double-blind,
      placebo controlled trials that analyzed the use of thyroid hormone analog for the
      treatment of dyslipidemia in humans were included. Finally, the ongoing research
      on the use of TR agonists was searched, searching the US National Institutes of
      Health Registry and the WHO International Clinical Trial Registry Platform
      (ICTRP). RESULTS: Thyromimetics were tested in humans for the treatment of
      dyslipidemia, as a single therapeutic agent or as an add-on therapy to the
      traditional lipid-lowering drugs. In most trials, thyromimetics lowered total
      cholesterol, low-density lipoprotein cholesterol, and triglycerides, but their
      use has been associated with adverse side-effects, both in pre-clinical studies
      and in humans. CONCLUSIONS: The use of thyromimetics for the treatment of
      dyslipidemia is not presently recommended. Future possible clinical applications
      might include their use to promote weight reduction. Thyromimetics might also
      represent an interesting alternative, both for the treatment of non-alcoholic
      steatohepatitis, and type 2 diabetes due to their positive effects on insulin
      sensitivity. Finally, additional experimental and clinical studies are needed for
      a better comprehension of the effect(s) of a long-term therapy.

PMID- 28498023
TI  - Physical and/or Sexual Abuse Is Associated with Increased Psychological and
      Emotional Distress Among Transgender Women.
AB  - PURPOSE: Transgender women have consistently reported elevated rates of lifetime
      physical and sexual abuse. This study examined the associations between reported
      physical and/or sexual abuse and symptoms of psychological and emotional distress
      among a sample of urban, high-risk transgender women. METHODS: From June 2005
      through July 2012, 99 transgender women enrolled in a Comprehensive Risk
      Counseling and Services program in Hollywood, CA. Seemingly unrelated regression
      equations (SURE) were used to simultaneously regress psychiatric symptom reports
      on participant sociodemographic characteristics and self-reported history of
      physical/sexual abuse. RESULTS: Participants were African American/Black (33.3%),
      Caucasian/White (28.3%), or Hispanic/Latina (24.2%). Average age was 35 years
      (standard deviation [SD] = 9), and 37.4% of participants self-reported an HIV
      positive status. Most (84.9%) participants reported experiencing physical or
      sexual abuse at some point in their lifetime, and symptoms of psychological and
      emotional distress (as measured by the Brief Symptom Inventory) among those who
      reported abuse were more severe than those observed in cisgender psychiatric in
      patient populations. After controlling for participant sociodemographics, prior
      experience of physical and/or sexual abuse was associated with significantly
      increased psychological and emotional distress across all measured symptom
      domains except psychoticism [chi2(9) = 17.56; p < 0.05]. CONCLUSION: Given these
      associations as well as the high prevalence of physical and/or sexual abuse among
      transgender women, mental health professionals and social service providers
      working with this population should be sensitive to the abuse history and mental
      health needs of the transgender women with whom they work.

PMID- 28498024
TI  - A prospective risk assessment of informal carers' medication administration
      errors within the domiciliary setting.
AB  - Increasingly, medication is being administered at home by family and friends of
      the care-recipient. This study aims to identify and analyse risks associated with
      potential drug administration errors made by informal carers at home. We mapped
      medication administration at home with a multidisciplinary team that included
      carers, health care professionals and patients. Evidence-based risk-analysis
      methodologies were applied: Healthcare Failure Modes and Effect Analysis (HFMEA),
      Systematic Human Error Reduction and Prediction Analysis (SHERPA) and Systems
      Theoretic Accident Model and Processes (STAMP). The process of administration
      comprises seven sub-processes. Thirty-four possible failure modes were identified
      and six of these were rated as high risk. These highlighted that medications may
      be given with a wrong dose, stored incorrectly, not discontinued as instructed,
      not recorded, or not ordered on time, and often caused by communication and
      support problems. Combined risk analyses contributed unique information helpful
      to better understand the medication administration risks and causes within
      homecare. Practitioner Summary: Increasingly, medication is being administered at
      home by family and friends of the care-recipient. This study identifies risks
      associated with potential drug administration errors made by informal carers at
      home through consensus-based quantitative techniques. The different analyses
      contribute unique information helpful to better understand the administration
      risks and causes.

PMID- 28498025
TI  - Understanding meaning in life interventions in patients with advanced disease: A
      systematic review and realist synthesis.
AB  - BACKGROUND: Among patients with advanced disease, meaning in life is thought to
      enhance well-being, promote coping and improve the tolerance of physical
      symptoms. It may also act as a buffer against depression and hopelessness. As
      yet, there has been no synthesis of meaning in life interventions in which
      contextual factors, procedures and outcomes are described and evaluated. AIMS: To
      identify meaning in life interventions implemented in patients with advanced
      disease and to describe their context, mechanisms and outcomes. DESIGN:
      Systematic review according to Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines and realist synthesis of meaning in life
      interventions using criteria from the Realist And Meta-narrative Evidence
      Syntheses: Evolving Standards project. DATA SOURCES: The CINAHL, PsycINFO, PubMed
      and Web of Science databases were searched. RESULTS: A total of 12 articles were
      included in the systematic review, corresponding to nine different interventions.
      Five articles described randomized controlled trials, two were qualitative
      studies, two were commentaries or reflections, and there was one pre-post
      evaluation, one exploratory study and one description of a model of care.
      Analysis of context, mechanisms and outcomes configurations showed that a core
      component of all the interventions was the interpersonal encounter between
      patient and therapist, in which sources of meaning were explored and a sense of
      connectedness was re-established. Meaning in life interventions were associated
      with clinical benefits on measures of purpose-in-life, quality of life, spiritual
      well-being, self-efficacy, optimism, distress, hopelessness, anxiety, depression
      and wish to hasten death. CONCLUSION: This review provides an explanatory model
      of the contextual factors and mechanisms that may be involved in promoting
      meaning in life. These approaches could provide useful tools for relieving
      existential suffering at the end of life.

PMID- 28498026
TI  - The Development of Palliative Care in Argentina: A Mapping Study Using Latin
      American Association for Palliative Care Indicators.
AB  - BACKGROUND: The Latin American Association for Palliative Care (ALCP) developed
      10 indicators to monitor the development of palliative care. The indicators have
      been applied across Latin American countries but have not been used internally.
      OBJECTIVE: The aims of this study were to document the development of palliative
      care in Argentina at the national and provincial levels by using a selection of
      the indicators developed by the ALCP and identify the difficulties and needs of
      healthcare professionals working in palliative care. This is the first study to
      apply the indicators intranationally. METHODS: This was a cross-sectional pilot
      study based on two questionnaires with representatives from each province, one
      workshop, and telephone conversations to corroborate the collected data. These
      data were used to calculate a preselection of eight ALCP indicators covering four
      main areas of development: education, policy, service delivery, and medication. A
      total of 30 participants took part in the study. RESULTS: The application of the
      ALCP indicators at the province level led to the identification of inequalities
      in the development and distribution of services across the country. The provinces
      in the north-west were identified as the region with the greatest need for
      development. The main difficulties for healthcare professionals were lack of
      national service registries, certified palliative care specialties, and
      opportunities for continuous training. DISCUSSION: The ALCP indicators are useful
      tools for mapping palliative care development within countries. Further work
      needs to be carried out to increase their specificity and integrate them in
      policy design and service delivery.

PMID- 28498027
TI  - Asthma and early herniated intervertebral disc disease.
AB  - BACKGROUND: The etiology of herniated intervertebral disc (HIVD) disease in
      children and adolescents is multifactorial and not merely related to disc
      degeneration. Therefore, in the present study, we investigated the relationship
      between young asthma patients and the risk of early HIVD disease in a population
      under 30 years of age. METHODS: Data from the National Health Insurance Research
      Database (NHIRD) of Taiwan were used to conduct a retrospective longitudinal
      cohort study. The study cohort comprised 23,470 patients with asthma (asthma
      group) and 23,470 patients without asthma (non-asthma group), who were selected
      through frequency matching on the basis of sex, age, and the index year. The
      study patients were followed until HIVD disease occurrence, withdrawal from the
      National Health Insurance program, or 31 December 2013. Cox proportional hazards
      regression analysis was conducted to assess the risk of HIVD disease in the
      asthma group after adjustment for sex, age, and comorbidities. RESULTS: After
      adjustment for sex, age, and comorbidities, the asthma group had a 1.69-fold (95%
      confidence interval [CI] = 1.29-2.23) higher risk of HIVD disease than did the
      non-asthma group. In addition, the asthma group had a higher risk of cervical and
      lumbar HIVD diseases than did the non-asthma group (adjusted hazard ratio [HR] =
      2.38; 95% CI = 1.25-4.57 and adjusted HR = 1.56; 95% CI = 1.15-2.12,
      respectively). CONCLUSIONS: Young patients with asthma are at a significantly
      higher risk of early cervical or lumbar HIVD disease.

PMID- 28498028
TI  - miR-337 can be a key negative regulator in melanoma.
AB  - Incidence of melanoma is increasing annually worldwide. There remains a lack of
      suitable treatment methods which can significantly improve the 5-year survival
      rates of patients. It is established that micro RNAs (miRNAs) have important
      roles in the diagnosis and treatment of cancer. MiR-337 had been reported to
      regulate the development of variety of cancers, as a cancer suppressive factor.
      In our research we found that miR-337 had a lower expression in melanoma than
      adjacent tissues. The patients who had a lower miR-337 also got a worse survival.
      MiR-337 could target STAT3 to regulate the occurrence and development of
      melanoma.  In summary, our findings suggest that the miR-337/STAT3 axis may serve
      as a potential target for the treatment of melanoma.

PMID- 28498029
TI  - Is one day off sufficient for re-adaptation to a daytime routine after two
      consecutive nights of work?
AB  - Fast rotation three-shift working schedules are common in the medical field in
      Taiwan. This study investigated whether 24 h off is sufficient for re-adaptation
      to a daytime routine after working two night shifts (NSs) by comparing changes in
      cognitive function, anxiety state and objectively measured sleep propensity
      between those working two NSs followed by 24 h off (n = 21, 2NS-off) and an off
      duty group (n = 21, OD). The results showed that nurses in the 2NS-off group were
      less alert and had decreased visual attention performance and executive function
      ability than the OD group during the daytime. One day off appeared to be
      insufficient to adapt back to a daytime shift after two NSs. Further studies are
      warranted to investigate whether a longer sequence of consecutive NSs (e.g. four
      NSs) followed by two days off is suitable for a fast rotation three-shift work
      schedule to allow for optimal performance throughout the next daytime shift.
      Practitioner Summary: The medical field in Taiwan mandates at least 24 h off
      between night and day shifts, but this appears to be insufficient for re-adapting
      to a daytime shift after two night shifts. A longer sequence of consecutive night
      shifts followed by two days off may be more suitable.

PMID- 28498030
TI  - Prevalence of anemia and its influence on hospital readmissions and emergency
      department visits in outpatients with heart failure.
AB  - BACKGROUND: Anemia is a frequent comorbidity in patients with heart failure.
      However, the incidence of anemia in patients with heart failure varies widely,
      and there is limited evidence on the association between anemia and
      rehospitalization and on the health consequences of anemia in patients with heart
      failure. AIMS: We aimed to identify the prevalence of anemia and its influence on
      hospital readmissions and emergency department visits in outpatients with heart
      failure. METHODS: This cross-sectional study included 284 patients with heart
      failure diagnosed at outpatient cardiology clinics at a tertiary care university
      hospital in Cheonan, South Korea. We obtained socio-demographic and clinical
      information, including frequency of readmissions and emergency department visits,
      using face-to-face interviews and medical record reviews. RESULTS: The prevalence
      of anemia, defined based on World Health Organization guidelines, was 39.1% among
      patients with heart failure. Anemia was significantly more prevalent among
      patients with one or more re-admissions or emergency department visits compared
      with patients with no history of hospital re-admissions or emergency department
      visits (42.7% vs. 13.9% ( p = 0.001) and 55.1% vs. 34% ( p = 0.002)
      respectively). Anemia increased the risk of hospital readmission (odds ratio
      =8.04, 95% confidence interval, 2.19-29.54) and emergency department visit (odds
      ratio=2.37, 95% confidence interval, 1.22-4.60) in patients with heart failure.
      CONCLUSION: It is imperative that patients with heart failure presenting with
      anemia undergo appropriate nursing assessment and intervention. Future
      prospective studies targeting interventions to improve anemia are required to
      determine whether anemia influences readmission rates and emergency department
      visits.

PMID- 28498031
TI  - Diagnosis and Management of Malignant Melanoma in Store-and-Forward
      Teledermatology.
AB  - BACKGROUND: Published studies have led to concern that store-and-forward
      teledermatology (SFT) diagnosis and management of melanomas may be inferior to
      face-to-face (FTF) dermatology care. INTRODUCTION: To ascertain the frequency of
      correctly managed and diagnosed melanomas within a population of veterans in
      Veterans Integrated Service Network 20 SFT. MATERIALS AND METHODS: We conducted a
      retrospective chart review of 7,960 veterans seen by SFT between July 1, 2009 and
      December 31, 2011. RESULTS: Of the 61 veterans that met inclusion and exclusion
      criteria, 45 (74%) melanomas were correctly diagnosed and 57 (93%) were correctly
      managed. DISCUSSION: Diagnostic and management accuracy of SFT is comparable to
      FTF. Incorrect diagnosis or management of melanomas did not prove to have
      significant consequences for patient care. Cases subject to analysis of this
      study are not demographically representative of the general population.
      CONCLUSION: Diagnosis and management of melanoma in SFT is comparable to FTF
      care.

PMID- 28498032
TI  - The Experiences of Reciprocity among Filipino Older Adults in Canada:
      Intergenerational, Transnational, and Community Considerations.
AB  - This article illustrates the concept of reciprocity in the context of immigrant
      families. It recommends that definition of reciprocity account for exchanges
      beyond the immediate family, and render visible the simultaneous location of
      older people as care recipients and providers, and care arrangements across
      generations, borders, community, and time. Adopting a critical ethnographic study
      on the aging and care experiences of older Filipinos in Canada, this article
      analyzes data from extended observations and in-depth semi-structured interviews
      with 18 older people, 6 adult children, and 13 community stakeholders. Findings
      highlight the unique configurations of care among the Filipino community whereby
      older people engage in care exchange as active participants across
      intergenerational, transnational, and fictive kin networks.

PMID- 28498033
TI  - Development and Characterization of Novel Monoclonal Antibodies Against Human
      DNAM-1.
AB  - DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and
      myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an
      important role in tumor immunity mediated by CD8+ T cells and NK cells. Moreover,
      the interaction of DNAM-1 with the ligands contributed to the development of
      acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal
      antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting
      that DNAM-1 may be a good molecular target for therapy to acute GVHD in human. In
      this study, we generated and characterized five novel clones of anti-human DNAM-1
      mAbs, named TX94, TX95, TX96, TX107, and TX108. Among these mAbs, TX94 is a
      unique neutralizing mAb that most efficiently blocked the interaction between
      DNAM-1 and CD155. Furthermore, TX94 inhibited NK cell-mediated cytotoxicity
      against a tumor cell line and suppressed CD8+ T cell proliferation mediated by
      allogeneic mixed lymphocyte reaction. Thus, TX94 may be useful for molecular
      therapy targeting DNAM-1.

PMID- 28498034
TI  - Assessment of Resident Physicians' Communicator and Collaborator Competencies by
      Interprofessional Clinicians: A Mixed-Methods Study.
AB  - : Phenomenon: As we move toward competency-based medical education, greater
      emphasis is being placed on assessing a more comprehensive skill set, including
      the ability to communicate and collaborate effectively in the workplace.
      Nonphysician members on interprofessional (IP) teams have valuable perspectives
      on actual resident performance and are often not adequately engaged in the
      provision of feedback to residents. Based on the educational theories of
      collaborative evaluation and social constructivism, this research examined the
      ability of IP clinicians to provide feedback to residents. The aim of this study
      was to examine IP clinicians' perceptions of their ability to provide formative
      feedback, through their observations and assessments of developmental pediatric
      residents, compared to physician supervisors on the rotation, and to
      qualitatively explore potential barriers to the feedback process from their
      perspective. APPROACH: This explanatory, sequential mixed-methods design study
      first examined which and how many of the CanMEDS Communicator and Collaborator
      training objectives (N = 40) were considered to be observable and assessable by
      IP clinicians and physicians. A comparison of the mean number of objectives that
      were observed and practically assessed by (a) each group (IP clinicians vs.
      physicians) and (b) clinical service teams during the core developmental
      pediatrics rotations, were examined using independent t tests. Second, a thematic
      qualitative analysis of focus groups was used to develop a contextual
      understanding of the factors that influenced this process. Data were analyzed
      using three levels of open coding and descriptive qualitative analysis
      techniques. FINDINGS: Physicians reported they could observe (M = 33.3, SD = 5.2,
      83.3%) and assess (M = 31.5, SD = 7.3, 79%) a larger number of objectives
      compared to the IP clinician group (M = 24.7, SD = 8.6, 61.8% and M = 20.3, SD =
      10.6, 51%, respectively). There were no differences between the clinical service
      teams (i.e., preschool/school-age and pediatric rehabilitation). The objective
      that was most observable and assessable by the IP clinicians was "Demonstrates a
      respectful attitude towards other colleagues and members of an interprofessional
      team." Four themes identified by the IP clinicians provided more in-depth
      qualitative information: (a) assessment requires more than simple observation,
      (b) assumptions and indirect observation influence assessment, (c) clinic culture
      and structure shapes observation and assessment, and (d) specific assessment
      criteria are required by IP clinicians. Insights: IP clinicians have the desire
      and ability to provide formative feedback to residents. Formalized processes with
      specific evaluation criteria would facilitate meaningful feedback from IP
      clinicians in the assessment of residents as they journey toward competence.

PMID- 28498036
TI  - Combination radiotherapy and cantharidin inhibits lung cancer growth through
      altering tumor infiltrating lymphocytes.
AB  - This study aimed to detect the effect of combination radiotherapy and cantharidin
      on lung cancer growth. We found that combination therapy with radiotherapy and
      cantharidin was more effective in inhibiting the tumor growth than radiotherapy
      or cantharidin alone. It decreased the percentage of CD4+ Tregs and enhanced the
      percentage of CD8+ T cells, CD4+ Teff cells when comparing to that of single
      treatment. Combination therapy promoted a great increase in double producing CD8+
      T cells and CD4+ Teff cells in tumor infiltrating lymphocytes. Overexpression of
      CTLA4 reversed the inhibitory action of combination treatment on cancer growth.
      Our data suggest that combining radiotherapy and cantharidin may have synergistic
      effects in driving tumor rejection by increasing T-cell infiltration,
      proliferation and cytokine production.

PMID- 28498035
TI  - Assessment of older adults' satisfaction with adult protective services
      investigation and assistance.
AB  - This study examined elder self-neglect client satisfaction with services provided
      by an Adult Protective Services (APS) program. A total of 77 community-dwelling
      older adults with APS-substantiated self-neglect responded to the standardized
      and widely used 8-item Client Satisfaction Questionnaire. Approximately 75% of
      the participants reported being satisfied with the overall services. They felt
      that the services provided were responsive to their need(s) and helped them deal
      with their problem(s). Greater than 80% responded that they would refer a friend,
      would utilize APS in the future if necessary, and were at least satisfied with
      the amount of help received. The extent to which their needs were met received
      the lowest satisfaction scores. Future studies are needed to examine elder self
      neglect client satisfaction in relation to specific services.

PMID- 28498037
TI  - Do parental decision-making patterns predict compliance with use of child booster
      seats?
AB  - Booster seat use for 4-9 year olds remains the lowest of all age groups in many
      countries. The objective of this study is to examine whether parents' decision
      making patterns, as measured by the Melbourne Decision Making Questionnaire,
      relate to car booster seat use. Israeli parents of 4-7 years old children (n =
      398) answered a questionnaire about car safety and decision-making habits. Ninety
      per cent of parents reported having a booster seat; 70.5% reported consistent
      booster seat use in general and on short drives during the last month (booster
      seat use compliance index). Greater compliance index was positively related to a
      vigilant decision-making pattern, passenger compliance with rear seat belts and
      families with fewer children. Lower booster seat use compliance index was
      associated with buck-passing decision-making pattern. Health professionals and
      policy-makers should take into account parents' habitual decision-making patterns
      when designing interventions for car booster seat compliance.

PMID- 28498038
TI  - Determination of Metal Elements in Wine Using Laser-Induced Breakdown
      Spectroscopy (LIBS).
AB  - We developed a method for sensitive elemental analysis of wines using laser
      induced breakdown spectroscopy (LIBS). In order to overcome the inefficiency of
      direct ablation of bulk wine (an organic liquid), a thin layer of wine residue
      was prepared on a metallic target according to an appropriated heating procedure
      applied to an amount of liquid wine dropped on the target surface. The obtained
      ensemble was thus ablated. Such a sample preparation procedure used a very small
      volume of 2 mL of wine and took only 30 min without reagent or solvent. The
      results show the detection of tens of metal and non-metal elements including
      majors (Na, Mg, K, Ca), minors, and traces (Li, B, Si, P, Ti, Mn, Fe, Cu, Zn, Rb,
      Sr, Ba, and Pb) in wines purchased from local supermarkets and from different
      production places in France. Commercially available wines were then spiked with
      certified standard solutions of Ti and Fe. Three series of laboratory reference
      samples were thus prepared using three different wines (a red wine and a white
      wine from a same production region and a red wine from another production region)
      with concentrations of Ti and Fe in the range of 1-40 mg/L. Calibration graphs
      established with the spiked samples allowed extracting the figures-of-merit
      parameters of the method for wine analysis such as the coefficient of
      determination ( R2) and the limits of detection and quantification (LOD and LOQ).
      The calibration curves built with the three wines were then compared. We studied
      the residual matrix effect between these wines in the determination of the
      concentrations of Ti and Fe.

PMID- 28498039
TI  - Seduction and the self: movements through precarity, race and sexuality in
      Japanese host clubs.
AB  - In this article, I build on the notion of precarity to argue that Japanese host
      clubs are sites in which a particular kind of intimacy and sense of 'belonging'
      are produced. The analysis highlights host clubs as necessary spaces among many
      in the precarious economy and as important venues for the production of
      subjectivity for the male hosts (both migrant and Japanese) as well as for the
      migrant women who frequent these establishments. In particular, host clubs
      provide a lucrative employment opportunity for young men - particularly young men
      who are migrants from the rural parts of Japan or the Philippines (and often
      Japanese-Filipino young men) who are trying to make a living in the context of
      what has been characterised as 'precarious Japan'. I draw on extended
      ethnographic fieldwork to show how the host clubs, though a part of the
      precarious economy, provide sites of home and belonging for both hosts and their
      clients.

PMID- 28498040
TI  - Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential
      of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue.
AB  - Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem
      cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate
      ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we
      determined whether ECT-cell content is a key determinant of its
      structure/function, thereby affecting ECT therapeutic potential for advanced
      heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or
      90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell
      sorting by using cardiac-specific markers. Notably, ECTs showed synchronized
      spontaneous beating when cardiomyocytes constituted >=50% of total cells, with
      the electrical-conduction velocity increasing depending on cardiomyocyte ratio;
      however, ECTs containing 90% cardiomyocytes failed to form stable structures.
      ECTs containing 25% or 50% cardiomyocytes predominantly expressed collagen and
      fibronectin, whereas ECTs containing 70% cardiomyocytes predominantly expressed
      laminin and exhibited the highest contractile/relaxation properties. Furthermore,
      transplantation of ECTs containing 50% or 70% cardiomyocytes into a rat chronic
      myocardial infarction model led to a more profound functional recovery as
      compared with controls. Notably, transplanted ECTs showed electrical
      synchronization with the native heart under Langendorff perfusion. Collectively,
      these results indicate that the quantity of non-cardiomyocytes is critical in
      generating functional iPSC-derived ECTs as grafts for cardiac-regeneration
      therapy, with ECTs containing 50-70% cardiomyocytes exhibiting stable structures
      and increased cardiotherapeutic potential.

PMID- 28498041
TI  - Sense of Community on Twitter and Instagram: Exploring the Roles of Motives and
      Parasocial Relationships.
AB  - Although research has explored the ways in which people form virtual communities
      to converse about media figures, television shows, and similar topics, little
      research has examined the link between virtual communities and the parasocial
      relationships (PSRs) that are often the focus of these conversations and users'
      experiences in those virtual communities. We examined sense of community (SOC) on
      Twitter and Instagram as a function of users' motives for use and users' PSR on
      the sites. In addition to examining the relative importance of different motives
      for using Twitter and Instagram, we predicted that PSR would mediate the
      association between motives for use and SOC. Results of an online survey revealed
      that Instagram users (n = 276) reported stronger social interaction motives than
      did Twitter users (n = 223). Social interaction and expressive information
      sharing motives were directly positively associated with SOC for users of both
      sites. Instagram users also exhibited indirect effects of expressive information
      sharing and companionship motives on SOC, through PSR. These findings suggest
      potentially influential differences between Twitter and Instagram, particularly
      regarding the role of PSR in fostering a general SOC.

PMID- 28498042
TI  - What Predicts Facebook Addiction?

PMID- 28498043
TI  - Pain and Pain Management Among University Students: Online Survey and Web-Based
      Education.
AB  - Pain is common among university students. Unrelieved pain has adverse impacts on
      their quality of life. In this study, a pain management Web site was developed to
      distribute an online survey and provide Web-based pain education to university
      students. Participants were recruited from eight universities in Hong Kong using
      snowball sampling. The online survey included 37 items examining pain situations,
      pain management strategies, knowledge about self-medication, and demographic data
      of the participants. A total of 387 students participated and over 90 percent of
      them reported pain in the past 6 months. Around one-third of participants did not
      take any action to manage their pain. Pharmacological method was the most common
      strategy for students to relieve pain (37.2 percent). The use of over-the-counter
      (OTC) drug for pain relief was high (n = 214). However, OTC drug knowledge score
      was significantly higher among health-related group than nonhealth-related group
      (p < 0.001). There were 188 students who also read the Web-based pain education
      and completed the evaluation on its usefulness. Nonhealth-related students
      reported significantly higher scores of self-perceived usefulness for the online
      education than the health-related students (p < 0.001). Findings suggested the
      need to consider the service users' background when developing online education
      program in the future.

PMID- 28498045
TI  - Problematic Video Game Play and ADHD Traits in an Adult Population.
AB  - This study examined the relationship between problematic video game play (PVGP),
      video game usage, and attention deficit hyperactivity disorder (ADHD) traits in
      an adult population. A sample of 205 healthy adult volunteers completed the Adult
      ADHD Self-Report Scale (ASRS), a video game usage questionnaire, and the Problem
      Video Game Playing Test (PVGT). A significant positive correlation was found
      between the ASRS and the PVGT. More specifically, inattention symptoms and time
      spent playing video games were the best predictors of PVGP. No relationship was
      found between frequency and duration of play and ADHD traits. Hyperactivity
      symptoms were not associated with PVGP. Our results suggest that there is a
      positive relationship between ADHD traits and problematic video game play. In
      particular, adults with higher level of self-reported inattention symptoms could
      be at higher risk of PVGP.

PMID- 28498046
TI  - Social Media Propagation of Content Promoting Risky Health Behavior.
AB  - While social media have been found useful in providing social support and health
      information, they have also been home to content advocating risky health
      behavior. This study focused on how content defending and even celebrating
      anorexia as a lifestyle are circulated among social media users, and investigates
      the characteristics that promote wide propagation of such messages. We captured
      anorexia-related content on Tumblr, a popular blog for talking about eating
      disorders, during a one-month period. Among the 35,432 posts collected, we
      examined the most highly propagated posts and coded them for message
      characteristics. Our findings revealed that posts in which the source of a
      narrative ("testimony") was identified (was either from an anorexic poster or
      about another's anorexia) and which were positive toward the pro-anorexia
      perspective were more likely to be propagated on Tumblr. In addition, posts
      containing content that references an anorexic person and contains an affective
      tone were more likely to be propagated. We also found that underweight bodies and
      bodies with a high degree of exposure were associated with propagation of posts.
      The present study suggested practical implications by focusing on the
      characteristics of highly propagated but potentially harmful content in social
      media.

PMID- 28498047
TI  - Fatal Attractions: Attachment to Smartphones Predicts Anthropomorphic Beliefs and
      Dangerous Behaviors.
AB  - As technology's presence grows increasingly concrete in global societies, so too
      do our relationships with the devices we keep close at hand from day to day.
      Whereas research has, in the past, framed smartphone addiction in terms of
      possessional attachment, the present research hypothesizes that anxious
      smartphone attachment stems from human attachment, in which Anxiously attached
      individuals may be more likely to generalize their anxious attachment style to
      communication devices. In the present study, we found support for this hypothesis
      and showed that anxious smartphone attachment predicts (1) anthropomorphic
      beliefs, (2) reliance on-or "clinginess" toward-smartphones, and (3) a seemingly
      compulsive urge to answer one's phone, even in dangerous situations (e.g., while
      driving). Taken together, we seek to provide a theoretical framework and
      methodological tools to identify the sources of technology attachment and those
      most at risk of engaging in dangerous or inappropriate behaviors as a result of
      attachment to ever-present mobile devices.

PMID- 28498049
TI  - The paradox of recognition: hijra, third gender and sexual rights in Bangladesh.
AB  - Hijra, the iconic figure of South Asian gender and sexual difference, comprise a
      publicly institutionalised subculture of male-bodied feminine-identified people.
      Although they have existed as a culturally recognised third gender for a very
      long time, it is only recently that hijra have been legally recognised as a third
      gender in several South Asian countries. This paper focuses on the transformation
      of this long-running cultural category of third gender into a legal category of
      third gender in Bangladesh, showing that the process of legal recognition has
      necessitated a simultaneous mobilisation of a discourse of disability in the
      constitution of hijra as citizens worthy of rights. While the international
      community views the recognition of a third gender as a progressive socio-legal
      advance in the obtaining of sexual rights in a Muslim majority Bangladesh,
      locally, hijra are understood as a special group of people born with 'missing' or
      ambiguous genitals delinked from desire. Furthermore, what was previously a trope
      of disfigurement based on putative genital status has now been transformed into a
      discourse of disability, a corollary to which several interest groups, namely the
      civil society, the state, international community and hijra themselves, have all
      been party.

PMID- 28498050
TI  - Quinone oxidoreductase 2 is involved in haustorium development of the parasitic
      plant Phtheirospermum japonicum.
AB  - The family Orobanchaceae includes many parasitic plant species. Parasitic plants
      invade host vascular tissues and form organs called haustoria, which are used to
      obtain water and nutrients. Haustorium formation is initiated by host-derived
      chemicals including quinones and flavonoids. Two types of quinone oxidoreductase
      (QR) are involved in signal transduction leading to haustorium formation; QR1
      mediates single-electron transfers and QR2 mediates 2-electron transfers. In the
      facultative parasite Triphysaria versicolor, QR1 is involved in haustorium
      induction signaling, while this role is played by QR2 in the model plant
      Phtheirospermum japonicum. Our results suggest that there is functional
      diversification in haustorium signaling molecules among different species of the
      Orobanchaceae.

PMID- 28498051
TI  - Editor's presentation.

PMID- 28498052
TI  - Decreased expression of MMP-9 in CD8+ cells in placenta with severe preeclampsia.
AB  - We compared the number of CD4-positive (CD4+) and CD8-positive (CD8+) cells in
      severe and non-severe preeclampsia (PE), and in normal pregnancy. We also
      evaluated the expression of matrix metalloproteinase 9 (MMP-9) in CD4+ and CD8+
      cells. Immunohistochemistry for CD4+ and CD8+ was performed on the decidua
      basalis of 15 severe and 13 non-severe PE women and compared to decidual tissue
      of 19 normal pregnancies (control group). Co-expression of MMP-9 with CD8+ and
      CD4+ cells was determined by double immunofluorescence staining. The median
      number of CD8+ cells/mm2 was significantly lower for the severe PE group than for
      the normal pregnancy group, as was the number of CD4+ cells and MMP-9+CD8+ cells.
      No statistical difference was found between the non-severe PE group and the
      normal pregnancy group. The significant decrease of CD4+, CD8+ and MMP-9+CD8+
      cells at the fetal-maternal interface only in the severe PE group suggests that
      immunological disorders play a role in the pathophysiology of severe PE.

PMID- 28498054
TI  - First clinical use of stereotaxy in humans: the key role of x-ray localization
      discovered by Gaston Contremoulins.
AB  - Although attempts to develop stereotactic approaches to intracranial surgery
      started in the late 19th century with Dittmar, Zernov, and more famously, Horsley
      and Clarke, widespread use of the technique for human brain surgery started in
      the second part of the 20th century. Remarkably, a significant similar surgical
      procedure had already been performed in the late 19th century by Gaston
      Contremoulins in France and has remained unknown. Contremoulins used the
      principles of modern stereotaxy in association with radiography for the first
      time, allowing the successful removal of intracranial bullets in 2 patients. This
      surgical premiere, greatly acknowledged in the popular French newspaper
      L'Illustration in 1897, received little scientific or governmental interest at
      the time, as it emanated from a young self-taught scientist without official
      medical education. This surgical innovation was only made possible financially by
      popular crowdfunding and, despite widespread military use during World War I,
      with 37,780 patients having benefited from this technique for intra- or
      extracranial foreign bodies, it never attracted academic or neurosurgical
      consideration. The authors of this paper describe the historical context of
      stereotactic developments and the personal history of Contremoulins, who worked
      in the department of experimental physiology of the French Academy of Sciences
      led by Etienne-Jules Marey in Paris, and later devoted himself to radiography and
      radioprotection. The authors also give precise information about his original
      stereotactic tool "the bullet finder" ("le chercheur de projectiles") and its key
      concepts.

PMID- 28498053
TI  - Autism Behavior Inventory: A Novel Tool for Assessing Core and Associated
      Symptoms of Autism Spectrum Disorder.
AB  - OBJECTIVE: Autism Behavior Inventory (ABI) is a new measure for assessing changes
      in core and associated symptoms of autism spectrum disorder (ASD) in participants
      (ages: 3 years-adulthood) diagnosed with ASD. It is a web-based tool with five
      domains (two ASD core domains: social communication, restrictive and repetitive
      behaviors; three associated domains: mental health, self-regulation, and
      challenging behavior). This study describes design, development, and initial
      psychometric properties of the ABI. METHODS: ABI items were generated following
      review of existing measures and inputs from expert clinicians. Initial ABI scale
      contained 161 items that were reduced to fit a factor analytic model, retaining
      items of adequate reliability. Two versions of the scale, ABI-full (ABI-F; 93
      items) and ABI-short version (ABI-S; 36 items), were developed and evaluated for
      psychometric properties, including validity comparisons with commonly used
      measures. Both scales were administered to parents and healthcare professionals
      (HCPs) involved with study participants. RESULTS: Test-retest reliability
      (intraclass correlation coefficient [ICC] = 0.79) for parent ratings on ABI was
      robust and compared favorably to existing scales. Test-retest correlations for
      HCP ratings were generally lower versus parent ratings. ABI core domains and
      comparison measures strongly correlated (r >= 0.70), demonstrating good
      concurrent validity. CONCLUSIONS: Overall, ABI demonstrates promise as a tool for
      measuring change in core symptoms of autism in ASD clinical studies, with further
      validation required.

PMID- 28498055
TI  - The intercostal nerve as a target for diagnostic biopsy.
AB  - OBJECTIVE Peripheral nerve biopsy is a useful tool in diagnosing peripheral
      neuropathies. Sural and gracilis nerves have become the most common targets for
      nerve biopsy. However, the yield of sural nerve biopsy is limited in patients who
      have motor neuropathies, and gracilis nerve biopsy presents technical challenges
      and increased complications. The authors propose the intercostal nerve as an
      alternative motor nerve target for biopsy. METHODS A total of 4 patients with
      suspected peripheral neuropathies underwent intercostal nerve biopsy at the
      authors' institution. A rib interspace that is inferior to the pectoralis muscle
      and anterior to the anterior axillary line is selected for the procedure.
      Generally the lower intercostal nerves (i.e., T7-11) are targeted. An incision is
      made over the inferior aspect of the superior rib at the chosen interspace. Blunt
      dissection is carried down to the neurovascular bundle and the nerve is isolated,
      ligated, and cut to send for pathological examination. RESULTS The average
      operative time for all cases was 73 minutes, with average blood loss of 8 ml.
      Biopsy results from 1 patient exhibited axonopathy, and the other 3 patients
      demonstrated axonopathy with demyelination. There were no short- or long-term
      postoperative complications. None of the patients reported sensory or motor
      deficits related to the biopsy at 6 weeks postoperatively. CONCLUSIONS The
      intercostal nerve can be an alternative target for biopsy, especially in patients
      with predominantly motor neuropathies, due to its mixed sensory and motor fibers,
      straightforward anatomy, minimal risk of serious sensory deficits, and no risk of
      motor impairment.

PMID- 28498056
TI  - Risk factors for surgical site infections and assessment of vancomycin powder as
      a preventive measure in patients undergoing first-time cranioplasty.
AB  - OBJECTIVE Craniectomy is often performed to decrease intracranial pressure
      following trauma and vascular injuries. The subsequent cranioplasty procedures
      may be complicated by surgical site infections (SSIs) due to prior trauma,
      foreign implants, and multiple surgeries through a common incision. Several
      studies have found that intrawound vancomycin powder (VP) is associated with
      decreased risk of SSIs after spine operations. However, no previously published
      study has evaluated the effectiveness of VP in cranioplasty procedures. The
      purpose of this study was to determine whether intrawound VP is associated with
      decreased risk of SSIs, to evaluate VP's safety, and to identify risk factors for
      SSIs after cranioplasty among patients undergoing first-time cranioplasty.
      METHODS The authors conducted a retrospective cohort study of adult patients
      undergoing first-time cranioplasty for indications other than infections from
      January 1, 2008, to July 31, 2014, at an academic health center. Data on
      demographics, possible risk factors for SSIs, and treatment with VP were
      collected from the patients' electronic health records. RESULTS During the study
      period, 258 patients underwent first-time cranioplasties, and 15 (5.8%) of these
      patients acquired SSIs. Ninety-two patients (35.7%) received intrawound VP (VP
      group) and 166 (64.3%) did not (no-VP group). Patients in the VP group and the no
      VP group were similar with respect to age, sex, smoking history, body mass index,
      and SSI rates (VP group 6.5%, no-VP group 5.4%, p = 0.72). Patients in the VP
      group were less likely than those in the no-VP group to have undergone
      craniectomy for tumors and were more likely to have an American Society of
      Anesthesiologists physical status score > 2. Intrawound VP was not associated
      with other postoperative complications. Risk factors for SSI from the bivariable
      analyses were diabetes (odds ratio [OR] 3.65, 95% CI 1.07-12.44), multiple
      craniotomy procedures before the cranioplasty (OR 4.39, 95% CI 1.47-13.18), prior
      same-side craniotomy (OR 4.73, 95% CI 1.57-14.24), and prosthetic implants (OR
      4.51, 95% CI 1.40-14.59). The multivariable analysis identified prior same-side
      craniotomy (OR 3.37, 95% CI 1.06-10.79) and prosthetic implants (OR 3.93, 95% CI
      1.15-13.40) as significant risk factors for SSIs. After adjusting for potential
      confounders, patients with SSIs were more likely than those without SSIs to be
      readmitted (OR 7.28, 95% CI 2.07-25.60). CONCLUSIONS In this study, intrawound VP
      was not associated with a decreased risk of SSIs or with an increased risk of
      complications. Prior same-side craniotomy and prosthetic implants were risk
      factors for SSI after first-time cranioplasty.

PMID- 28498057
TI  - Stereotactic radiosurgery alone or combined with embolization for brain
      arteriovenous malformations: a systematic review and meta-analysis.
AB  - OBJECTIVE Embolization of brain arteriovenous malformations (AVMs) prior to
      stereotactic radiosurgery (SRS) has been reported to negatively affect
      obliteration rates. The goal of this systematic review and meta-analysis was to
      compare the outcomes of AVMs treated with embolization plus SRS (E+SRS group) and
      those of AVMs treated with SRS alone (SRS group). METHODS A literature review was
      performed using PubMed to identify studies with 10 or more AVM patients and
      obliteration data for both E+SRS and SRS groups. A meta-analysis was performed to
      compare obliteration rates between the E+SRS and SRS groups. RESULTS Twelve
      articles comprising 1716 patients were eligible for analysis. Among the patients
      with radiological follow-up data, complete obliteration was achieved in 48.4% of
      patients (330/681) in the E+SRS group compared with 62.7% of patients (613/978)
      in the SRS group. A meta-analysis of the pooled data revealed that the
      obliteration rate was significantly lower in the E+SRS group (OR 0.51, 95% CI
      0.41-0.64, p < 0.00001). Symptomatic adverse radiation effects were observed in
      6.6% (27/412 patients) and 11.1% (48/433 patients) of the E+SRS and SRS groups,
      respectively. The annual post-SRS hemorrhage rate was 2.0%-6.5% and 0%-2.0% for
      the E+SRS and SRS groups, respectively. The rates of permanent morbidity were 0%
      6.7% and 0%-13.5% for the E+SRS and SRS groups, respectively. CONCLUSIONS
      Arteriovenous malformation treatment with combined embolization and SRS is
      associated with lower obliteration rates than those with SRS treatment alone.
      However, this comparison does not fully account for differences in the initial
      AVM characteristics in the E+SRS group as compared with those in the SRS group.
      Further studies are warranted to address these limitations.

PMID- 28498058
TI  - Endoscopic endonasal resection of the odontoid process: clinical outcomes in 34
      adults.
AB  - OBJECTIVE Treatment of odontoid disease from a ventral corridor has consisted of
      a transoral approach. More recently, the endoscopic endonasal approach (EEA) has
      been used to access odontoid pathology. METHODS A retrospective review was
      conducted of patients who underwent an EEA for odontoid pathology from 2004 to
      2013. During our analysis, the mean follow-up duration was 42.6 months (range 1
      80 months). Patient outcomes, complications, and postoperative swallowing
      function were assessed either by clinic visit or phone contact. RESULTS Thirty
      four patients underwent an EEA for symptomatic odontoid pathology. The most
      common pathology treated was basilar invagination (n = 17). Other pathologies
      included odontoid fractures, os odontoideum, and metastatic carcinoma. The mean
      patient age was 71.5 years. Thirty-one patients underwent a posterior fusion. All
      34 patients experienced stability or improvement in symptoms and all had
      successful radiographic decompression. The overall complication rate was 76%.
      Nearly all of these complications were transient (86%) and the overall
      complication rate excluding mild transient dysphagia was only 44%. Twenty-one
      patients (62%) suffered from transient postoperative dysphagia: 15 cases were
      mild, transient subjective dysphagia (6 of whom had documented preoperative
      dysphagia), whereas 6 other patients required tube feedings for decreased oral
      intake, malnutrition, and dysphagia in the perioperative setting (5 of these
      patients had documented preoperative dysphagia). Sixteen patients had documented
      preoperative dysphagia and 6 of these had lower cranial nerve dysfunction.
      Postoperatively, 6 (37.5%) of 16 patients with preoperative dysphagia and 4 (67%)
      of 6 with lower cranial nerve dysfunction had significant dysphagia/respiratory
      complications. Eighteen patients had no documented preoperative dysphagia and
      only 2 had significant postoperative dysphagia/respiratory complications (11%).
      The rates of these complications in patients without preoperative dysphagia were
      lower than in those with any preoperative dysphagia (p = 0.07) and especially
      those with preexisting lower cranial neuropathies (p = 0.007). Dysphagia was also
      significantly more common in patients who underwent occipitocervical fixation
      (19/26, 73%) than in patients who underwent cervical fusion alone or no fusion
      (2/8, 25%; p = 0.02). All patients with perioperative dysphagia had improved at
      follow-up and all patients were tolerating oral diets. No patient suffered from
      velopalatal insufficiency. Two patients had intraoperative CSF leaks. One of
      these patients underwent a negative exploratory surgery for a questionable
      postoperative CSF leak. One patient developed infection in the resection bed
      requiring debridement and antibiotics. One patient died 8 days following surgery
      from an unknown cause. The 90-day perioperative mortality rate was 2.9%.
      CONCLUSIONS A completely EEA can be performed for compressive odontoid disease in
      all cases of neoplastic, degenerative, or invaginative atlantoaxial disease with
      satisfactory outcomes and low morbidity. Transient perioperative dysphagia and
      respiratory complications are common, usually as an exacerbation and reflection
      of underlying disease or occipitocervical fusion rather than the EEA, emphasizing
      the importance of avoiding transoral surgery.

PMID- 28498059
TI  - Oligodendroglioma resection: a Surveillance, Epidemiology, and End Results (SEER)
      analysis.
AB  - OBJECTIVE The available evidence suggests that the clinical benefits of extended
      resection are limited for chemosensitive tumors, such as primary CNS lymphoma.
      Oligodendroglioma is generally believed to be more sensitive to chemotherapy than
      astrocytoma of comparable grades. In this study the authors compare the survival
      benefit of gross-total resection (GTR) in patients with oligodendroglioma
      relative to patients with astrocytoma. METHODS Using the Surveillance,
      Epidemiology, and End Results (SEER) Program (1999-2010) database, the authors
      identified 2378 patients with WHO Grade II oligodendroglioma (O2 group) and 1028
      patients with WHO Grade III oligodendroglioma (O3 group). Resection was defined
      as GTR, subtotal resection, biopsy only, or no resection. Kaplan-Meier and
      multivariate Cox regression survival analyses were used to assess survival with
      respect to extent of resection. RESULTS Cox multivariate analysis revealed that
      the hazard of dying from O2 and O3 was comparable between patients who underwent
      biopsy only and GTR (O2: hazard ratio [HR] 1.06, 95% confidence interval [CI]
      0.73-1.53; O3: HR 1.18, 95% CI 0.80-1.72). A comprehensive search of the
      published literature identified 8 articles without compelling evidence that GTR
      is associated with improved overall survival in patients with oligodendroglioma.
      CONCLUSIONS This SEER-based analysis and review of the literature suggest that
      GTR is not associated with improved survival in patients with oligodendroglioma.
      This finding contrasts with the documented association between GTR and overall
      survival in anaplastic astrocytoma and glioblastoma. The authors suggest that
      this difference may reflect the sensitivity of oligodendroglioma to chemotherapy
      as compared with astrocytomas.

PMID- 28498060
TI  - Correlation between reduction in microvascular transit time after superficial
      temporal artery-middle cerebral artery bypass surgery for moyamoya disease and
      the development of postoperative hyperperfusion syndrome.
AB  - OBJECTIVE Hyperperfusion syndrome (HPS) is a notable complication that causes
      various neurological symptoms after superficial temporal artery (STA)-middle
      cerebral artery (MCA) bypass surgery for moyamoya disease (MMD). The authors used
      intraoperative indocyanine green (ICG) videoangiography to measure the change in
      microvascular transit time (MVTT) after bypass surgery. An analysis was then
      conducted to identify the correlation between change in MVTT and presence of
      postoperative HPS. METHODS This study included 105 hemispheres of 81 patients
      with MMD who underwent STA-MCA single bypass surgery between January 2010 and
      January 2015. Intraoperative ICG videoangiography was performed before and after
      bypass surgery. The MVTT was calculated from the ICG time intensity curve
      recorded in the pial arterioles and venules. Multivariate logistic regression
      analysis was conducted to test the effect of multiple variables, including the
      change in MVTT after bypass surgery, on postoperative HPS. RESULTS Postoperative
      HPS developed in 28 (26.7%) of the 105 hemispheres operated on. MVTT was reduced
      significantly after bypass surgery (prebypass 5.34 +/- 2.00 sec vs postbypass
      4.12 +/- 1.60 sec; p < 0.001). The difference between prebypass and postbypass
      MVTT values, defined as DeltaMVTT, was significantly greater in the HPS group
      than in the non-HPS group (2.55 +/- 2.66 sec vs 0.75 +/- 1.78 sec; p < 0.001).
      Receiver operating characteristic curve analysis revealed that the optimal cutoff
      point of DeltaMVTT was 2.6 seconds (sensitivity 46.4% and specificity 85.7% as a
      predictor of postoperative HPS). A DeltaMVTT > 2.6 seconds was an independent
      predictor of HPS in multivariate analysis (hazard ratio 4.88, 95% CI 1.76-13.57;
      p = 0.002). CONCLUSIONS MVTT in patients with MMD was reduced significantly after
      bypass surgery. Patients with a DeltaMVTT > 2.6 seconds tended to develop
      postoperative HPS. Because DeltaMVTT can be easily measured during surgery, it is
      a useful diagnostic tool for identifying patients at high risk for HPS after STA
      MCA bypass surgery for MMD.

PMID- 28498061
TI  - Microvascular decompression for hemifacial spasm: can intraoperative lateral
      spread response monitoring improve surgical efficacy?
AB  - OBJECTIVE The purpose of this study was to evaluate whether intraoperative
      monitoring of lateral spread response (LSR) improves the efficacy of
      microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS In this
      prospective study, patients undergoing MVD for HFS were assigned to one of 2
      groups, Group A (MVD with intraoperative LSR monitoring) or Group B (MVD without
      LSR monitoring). Clinical outcome at 12 months after surgery was assessed through
      telephone survey. Data analysis was performed to investigate the effect of
      intraoperative LSR monitoring on efficacy of MVD. RESULTS A total of 283 patients
      were enrolled in the study, 145 in Group A and 138 in Group B. There was no
      statistically significant difference between the 2 groups with respect to the
      percentage of patients who had spasm relief at either 1 week (Group A 87.59% vs
      Group B 83.33%; p = 0.317) or 1 year (93.1% vs 94.2%; p = 0.809) after surgery. A
      clear-cut elimination of LSR during surgery was observed in 131 (90.34%) of 145
      patients; LSR persisted in 14 patients (9.66%) at the end of the surgical
      procedure. Disappearance of LSR correlated with spasm-free status at 1 week
      postoperatively (p = 0.017) but not at 1 year postoperatively (p = 0.249).
      CONCLUSIONS Intraoperative LSR monitoring does not appear to provide significant
      benefit with respect to the outcome of MVD for HFS in skilled hands. Persistence
      of LSR does not always correlate with poor outcome, and LSR elimination should
      not be pursued in all patients after verification of complete decompression.

PMID- 28498062
TI  - Telemedicine is helping the parents of children with neurodevelopmental disorders
      living in remote and deprived areas.
AB  - Telecommunication technologies are advancing rapidly with huge investment to
      improve infrastructure in rural areas. Telemedicine brings the benefits of
      telecommunication to healthcare, especially in resource-limited and remote
      communities. The recent literature on telemedicine in paediatrics will be
      reviewed, with particular focus on its application to help children with
      neurodevelopmental disorders and their families living in remote regions and/or
      low-income countries, and gaps identified for future research. Studies show that
      telemedicine can enable a family's access to appropriately qualified help that
      physically may only be available hundreds of miles away, helping to overcome
      geographic barriers. Telemedicine can also train parents and equip them with the
      knowledge and skills to better care for their children. Despite some
      technological barriers to implementation, telemedicine can help transform all
      stages of autism treatment. However, more studies are required in low- and middle
      income countries to fully elucidate the benefits offered by telemedicine to
      autistic children and their families.

PMID- 28498063
TI  - Preliminary Evaluation of a Novel Rigid Bronchoscopy Simulator.
AB  - PURPOSE: Emergent retrieval of airway foreign bodies (AFBs) in children remains a
      priority skill set for pediatric surgeons. In the setting of low procedural
      volume, simulation-based education with deliberate practice is essential to
      ensure trainees reach expected surgical competency. The purposes of this work
      were to (1) create a realistic rigid bronchoscopy for AFB retrieval simulation
      model and (2) to evaluate preliminary validity evidence of a novel simulator for
      the use of training and assessing pediatric surgical trainees' rigid bronchoscopy
      skills. METHODS: After institutional review board exemption determination, 18
      participants performed AFB retrieval of two different objects on a novel
      simulator that represented an 18-month-old pediatric tracheobronchial airway.
      Participants reported their experience and comfort level, and rated the simulator
      across two domains-Authenticity and their Ability to perform tasks. Authenticity
      was measured by 23 items across five subdomains (Visual Attributes, Materials'
      Response, Realism of Experience, Value and Relevance, and Global Value).
      Participants who had previously performed >=10 rigid bronchoscopies were
      categorized as "experienced," while those reporting <10 were considered "novice."
      Validity evidence relevant to test content and internal structure was evaluated
      using a many-facet Rasch model. RESULTS: Novice surgeons (n = 12) had previously
      performed a mean of 2.7 (+/-2.0) rigid bronchoscopies, compared to 15.4 (+/-7.7)
      by experienced surgeons (n = 6). For both models, the Value and Relevance
      subdomain received the highest ratings (observed average [OA] = 3.9, while
      Materials' Response received the lowest (OA <3.0). Participants' Global Value
      rating for this model was consistent with "requires minor improvements before it
      can be considered for use in rigid bronchoscopy training." CONCLUSIONS: We
      successfully designed, assembled, and evaluated a novel pediatric rigid
      bronchoscopy model for AFB retrieval. The model was considered as relevant to
      educational needs and valuable as a testing and training tool. With recommended
      improvements, the model could be used for implementation with a Mastery Learning
      curriculum.

PMID- 28498064
TI  - Polydopamine/polyethyleneimine complex adhered to micrometer-sized magnetic
      carbon fibers for high-efficiency hemoperfusion.
AB  - Carbon-based nanomaterials have recently attracted tremendous attention in
      adsorption, separation and biological fields. However, such modification is not
      always straightforward when the surface is not chemically reactive. Given this
      reason, most carbon materials modification processes employ reactive linkers or
      coupling agents, which are complicated and time-consuming. Herein, we report on a
      dopamine-polyethyleneimine (PEI) coating strategy to fabricate micrometer-sized
      magnetic carbon fiber (MSMCF)-based extracorporeal blood-cleansing sorbent for
      hemoperfusion. Results showed that the dopamine/PEI-coated MSMCF had a twisted
      fiber shape with a size range of 80-120 MUm in diameter and porous structure with
      a specific surface area of 146 m2 g-1. Adsorption behavior of dopamine/PEI
      modified MSMCF was examined by using bilirubin as a toxin model compound.
      Equilibrium data were well fitted to the Langmuir isotherm model with a maximal
      adsorption capacity of 335.1 mg g-1 at ambient temperature. The as-obtained
      material had relatively high bilirubin adsorption selectivity against albumin at
      a normal albumin concentration. In particular, the dopamine/PEI-coated MSMCF has
      excellent adsorption capacity and hemocompatibility compared to the MSMCF
      decorated only by dopamine or PEI. Therefore, this work may pave the way for
      enhancing the property of the extracorporeal blood-cleansing sorbent during
      hemoperfusion.

PMID- 28498065
TI  - Effect of Interval and Continuous Aerobic Training on Basal Serum and Plasma
      Brain-Derived Neurotrophic Factor Values in Seniors: A Systematic Review of
      Intervention Studies.
AB  - The purpose of this systematic review was to provide a comprehensive analysis of
      the available clinical trials analyzing, in seniors, the effect of interval
      aerobic training (IAT) and continuous aerobic training (CAT) on peripheral brain
      derived neurotrophic factor (BDNF) concentration. We identified 14 randomized or
      not-randomized intervention studies published up to January 2017 through a
      computer-assisted search (PUBMED, Pedro, and Science direct data bases). The five
      trials considering IAT and the nine considering CAT totalized 988 individuals
      (age range: 58.1-77 years). The parameters of aerobic training (AT) protocol in
      terms of frequency and intensity are the primary determinants of the BDNF
      response to AT. The interpretation of the relationship between AT and BDNF
      signaling pathway was very challenging when specific health conditions were taken
      into consideration. This was more particularly true with mild cognitive
      impairment or depressive symptoms. These findings argue in favor of a
      generalization of the practice of AT and show that the type of training is not
      the main determining factor of the increase in BDNF level, which results more
      from the combination of several factors such as intensity and frequency of
      sessions, duration of programs, and also some genetic determinant coding for BDNF
      protein. All these factors have to be carefully addressed in future researches in
      that field. Thus, further researches are still necessary to better the signaling
      pathway by which AT contributes to better health outcomes.

PMID- 28498066
TI  - Atrial fibrillation in pregnancy: a growing challenge.
AB  - BACKGROUND: Atrial fibrillation (AF) constitutes a relatively infrequent
      pregnancy complication, which may be a therapeutic Gordian knot. Indeed, sparse
      data exist regarding the prevalence, prognosis, and management of AF during
      pregnancy. In general, AF occurs as a benign, self-limited arrhythmia, but
      occasionally may have severe hemodynamic consequences in pregnant patients
      suffering from heart failure, congenital heart disease, or other comorbidities.
      Extra-cardiac causes of AF should always be meticulously excluded. REVIEW:
      Treatment decisions are difficult, since medications may cross the placental
      barrier and potentially affect fetal growth and organogenesis, or even result in
      fetal bradyarrhythmias. Treatment goals are not differentiated in comparison to
      those regarding AF occurring in the general population. Still, while maternal
      treatment is prioritized, issues regarding fetal health must deliberately be
      considered. Consequently, hemodynamic instability is to be promptly treated with
      synchronized electrical cardioversion. In contrast, in stable patients,
      pharmacologic cardioversion, under appropriate antithrombotic regimen, should be
      attempted. Selection of appropriate antithrombotic therapy, including novel oral
      anticoagulants, imposes further difficulties on therapeutic decision-making.
      Further clinical trials are warranted in order to assess the pathophysiology and
      prognosis of AF in pregnancy and ameliorate the evidence-based therapeutic
      strategy in this specific group of the population.

PMID- 28498067
TI  - Characterization and migration of oil and solids in oily sludge during
      centrifugation.
AB  - The migration behaviors of oil, water and solids in sludge during centrifugation
      were elaborated. Size distribution, surface topography and lypohydrophilic
      properties were studied in detail. The average size of solids was 61 MUm in
      original sludge, 31 MUm in upper layer and 235 MUm in bottom layer. The result
      shows that solvent is essential to separate oil phase into molecular light and
      weight fractions during centrifugation. With solvent/oil ratio increases from
      1:2, 1:1, 2:1 to 5:1, molecular weight in upper layer decreases from 1044, 1043,
      1020 to 846 combined with that in bottom layer increases. A model was proposed to
      calculate the oil residue content in solid phases after sedimentation. The
      findings of this paper provide information for optimizing the oil recovery and
      clean treatment.

PMID- 28498068
TI  - Predictors of extended length of stay, discharge to inpatient rehab, and hospital
      readmission following elective lumbar spine surgery: introduction of the Carolina
      Semmes Grading Scale.
AB  - OBJECTIVE Extended hospital length of stay (LOS), unplanned hospital readmission,
      and need for inpatient rehabilitation after elective spine surgery contribute
      significantly to the variation in surgical health care costs. As novel payment
      models shift the risk of cost overruns from payers to providers, understanding
      patient-level risk of LOS, readmission, and inpatient rehabilitation is critical.
      The authors set out to develop a grading scale that effectively stratifies risk
      of these costly events after elective surgery for degenerative lumbar
      pathologies. METHODS The Quality and Outcomes Database (QOD) registry
      prospectively enrolls patients undergoing surgery for degenerative lumbar spine
      disease. This registry was queried for patients who had undergone elective 1- to
      3-level lumbar surgery for degenerative spine pathology. The association between
      preoperative patient variables and extended postoperative hospital LOS (LOS >= 7
      days), discharge status (inpatient facility vs home), and 90-day hospital
      readmission was assessed using stepwise multivariate logistic regression. The
      Carolina-Semmes grading scale was constructed using the independent predictors
      for LOS (0-12 points), discharge to inpatient facility (0-18 points), and 90-day
      readmission (0-6 points), and its performance was assessed using the QOD data
      set. The performance of the grading scale was then confirmed separately after
      using it in 2 separate neurosurgery practice sites (Carolina Neurosurgery & Spine
      Associates [CNSA] and Semmes Murphey Clinic). RESULTS A total of 6921 patients
      were analyzed. Overall, 290 (4.2%) patients required extended LOS, 654 (9.4%)
      required inpatient facility care/rehabilitation on hospital discharge, and 474
      (6.8%) were readmitted to the hospital within 90 days postdischarge. Variables
      that remained as independently associated with these unplanned events in
      multivariate analysis included age >= 70 years, American Society of
      Anesthesiologists Physical Classification System class > III, Oswestry Disability
      Index score >= 70, diabetes, Medicare/Medicaid, nonindependent ambulation, and
      fusion. Increasing point totals in the Carolina-Semmes scale effectively
      stratified the incidence of extended LOS, discharge to facility, and readmission
      in a stepwise fashion in both the aggregate QOD data set and when subsequently
      applied to the CNSA/Semmes Murphey practice groups. CONCLUSIONS The authors
      introduce the Carolina-Semmes grading scale that effectively stratifies the risk
      of prolonged hospital stay, need for postdischarge inpatient facility care, and
      90-day hospital readmission for patients undergoing first-time elective 1- to 3
      level degenerative lumbar spine surgery. This grading scale may be helpful in
      identifying patients who may require additional resource utilization within a
      global period after surgery.

PMID- 28498069
TI  - An analysis from the Quality Outcomes Database, Part 2. Predictive model for
      return to work after elective surgery for lumbar degenerative disease.
AB  - OBJECTIVE Current costs associated with spine care are unsustainable.
      Productivity loss and time away from work for patients who were once gainfully
      employed contributes greatly to the financial burden experienced by individuals
      and, more broadly, society. Therefore, it is vital to identify the factors
      associated with return to work (RTW) after lumbar spine surgery. In this
      analysis, the authors used data from a national prospective outcomes registry to
      create a predictive model of patients' ability to RTW after undergoing lumbar
      spine surgery for degenerative spine disease. METHODS Data from 4694 patients who
      underwent elective spine surgery for degenerative lumbar disease, who had been
      employed preoperatively, and who had completed a 3-month follow-up evaluation,
      were entered into a prospective, multicenter registry. Patient-reported outcomes
      Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain (BP)
      and leg pain (LP), and EQ-5D scores-were recorded at baseline and at 3 months
      postoperatively. The time to RTW was defined as the period between operation and
      date of returning to work. A multivariable Cox proportional hazards regression
      model, including an array of preoperative factors, was fitted for RTW. The model
      performance was measured using the concordance index (c-index). RESULTS Eighty
      two percent of patients (n = 3855) returned to work within 3 months
      postoperatively. The risk-adjusted predictors of a lower likelihood of RTW were
      being preoperatively employed but not working at the time of presentation, manual
      labor as an occupation, worker's compensation, liability insurance for
      disability, higher preoperative ODI score, higher preoperative NRS-BP score, and
      demographic factors such as female sex, African American race, history of
      diabetes, and higher American Society of Anesthesiologists score. The likelihood
      of a RTW within 3 months was higher in patients with higher education level than
      in those with less than high school-level education. The c-index of the model's
      performance was 0.71. CONCLUSIONS This study presents a novel predictive model
      for the probability of returning to work after lumbar spine surgery. Spine care
      providers can use this model to educate patients and encourage them in shared
      decision-making regarding the RTW outcome. This evidence-based decision support
      will result in better communication between patients and clinicians and improve
      postoperative recovery expectations, which will ultimately increase the
      likelihood of a positive RTW trajectory.

PMID- 28498070
TI  - Extracranial internal carotid artery dissection caused by compression from a
      giant osteophyte due to atlantoaxial osteoarthritis: case report.
AB  - Deformed osseous structures have been reported as rare causes of extracranial
      internal carotid artery (ICA) dissection, including the styloid process and the
      hyoid bone. Here, the authors describe the first known case of symptomatic ICA
      dissection caused by a giant osteophyte due to atlantoaxial osteoarthritis. The
      left ICA was fixed at the skull base and at the ICA portion compressed by the
      osteophyte, and it was highly stretched and injured between the two portions
      during neck rotation. The patient was successfully treated with ligation of the
      affected ICA following balloon test occlusion. Atlantoaxial osteoarthritis should
      be considered in the differential diagnosis of ICA dissection in patients with a
      severely deformed cervical spine.

PMID- 28498071
TI  - Assessment of malpractice claims due to spinal epidural abscess.
AB  - OBJECTIVE Spinal epidural abscesses (SEAs) can be difficult to diagnose and may
      result in neurological compromise or even death. Delays in diagnosis or treatment
      may worsen the prognosis. While SEA presents a high risk for litigation, little
      is known about the medicolegal ramifications of this condition. An enhanced
      understanding of potential legal implications is important for practicing spine
      surgeons, emergency medicine physicians, and internists. METHODS The
      VerdictSearch database, a large legal-claims database, was queried for "epidural
      abscess"-related legal cases. Demographic and clinical data were examined for all
      claims; any irrelevant cases or cases with incomplete information were excluded.
      The effects of age of the plaintiff, sex of the plaintiff, presence of a known
      infection, resulting paraplegia or quadriplegia, delay in diagnosis, and delay in
      treatment on the proportion of plaintiff rulings and size of payments were
      assessed. RESULTS In total, 56 cases met the inclusion criteria. Of the 56 cases,
      17 (30.4%) were settled, 22 (39.3%) resulted in a defendant ruling, and 17
      (30.4%) resulted in a plaintiff ruling. The mean award for plaintiff rulings was
      $5,277,468 +/- $6,348,462 (range $185,000-$19,792,000), which was significantly
      larger than the mean award for cases that were settled out of court, $1,914,265
      +/- $1,313,322 (range $100,000-$4,500,000) (p < 0.05). The mean age of the
      plaintiffs was 47.0 +/- 14.4 years; 23 (41.1%) of the plaintiffs were female and
      33 (58.9%) were male. The proportion of plaintiff verdicts and size of monetary
      awards were not affected by age or sex (p > 0.49). The presence of a previously
      known infection was also not associated with the proportion of plaintiff verdicts
      or indemnity payments (p > 0.29). In contrast, juries were more likely to rule in
      favor of plaintiffs who became paraplegic or quadriplegic (p = 0.03) compared
      with plaintiffs who suffered pain or isolated weakness. Monetary awards for
      paraplegic or quadriplegic patients were also significantly higher (p = 0.003).
      Plaintiffs were more likely to win if there was a delay in diagnosis (p = 0.04)
      or delay in treatment (p = 0.006), although there was no difference in monetary
      awards (p > 0.57). Internists were the most commonly sued physician (named in 13
      suits [23.2%]), followed by emergency medicine physicians (named in 8 [14.3%]),
      and orthopedic surgeons (named in 3 [5.4%]). CONCLUSIONS This investigation is
      the largest examination of legal claims due to spinal epidural abscess to date.
      The proportion of plaintiff verdicts was significantly higher in cases in which
      the patient became paraplegic or quadriplegic and in cases in which there was
      delay in diagnosis or treatment. Additionally, paralysis is linked to large sums
      awarded to the plaintiff. Nonsurgeon physicians, who are often responsible for
      initial diagnosis, were more likely to be sued than were surgeons.

PMID- 28498072
TI  - Paravertebral foramen screw fixation for posterior cervical spine fusion:
      biomechanical study and description of a novel technique.
AB  - OBJECTIVE Fusion surgery with instrumentation is a widely accepted treatment for
      cervical spine pathologies. The authors propose a novel technique for subaxial
      cervical fusion surgery using paravertebral foramen screws (PVFS). The authors
      consider that PVFS have equal or greater biomechanical strength than lateral mass
      screws (LMS). The authors' goals of this study were to conduct a biomechanical
      study of PVFS, to investigate the suitability of PVFS as salvage fixation for
      failed LMS, and to describe this novel technique. METHODS The authors harvested
      24 human cervical spine vertebrae (C3-6) from 6 fresh-frozen cadaver specimens
      from donors whose mean age was 84.3 +/- 10.4 years at death. For each vertebra,
      one side was chosen randomly for PVFS and the other for LMS. For PVFS, a 3.2-mm
      drill with a stopper was advanced under lateral fluoroscopic imaging. The drill
      stopper was set to 12 mm, which was considered sufficiently short not to breach
      the transverse foramen. The drill was directed from 20 degrees  to 25 degrees 
      medially so that the screw could purchase the relatively hard cancellous bone
      around the entry zone of the pedicle. The hole was tapped and a 4.5-mm-diameter *
      12-mm screw was inserted. For LMS, 3.5-mm-diameter * 14-mm screws were inserted
      into the lateral mass of C3-6. The pullout strength of each screw was measured.
      After pullout testing of LMS, a drill was inserted into the screw hole and the
      superior cortex of the lateral mass was pried to cause a fracture through the
      screw hole, simulating intraoperative fracture of the lateral mass. After the
      procedure, PVFS for salvage (sPVFS) were inserted on the same side and pullout
      strength was measured. RESULTS The CT scans obtained after screw insertion
      revealed no sign of pedicle breaching, violation of the transverse foramen, or
      fracture of the lateral mass. A total of 69 screws were tested (23 PVFS, 23 LMS,
      and 23 sPVFS). One vertebra was not used because of a fracture that occurred
      while the specimen was prepared. The mean bone mineral density of the specimens
      was 0.29 +/- 0.10 g/cm3. The mean pullout strength was 234 +/- 114 N for PVFS,
      158 +/- 91 N for LMS, and 195 +/- 125 N for sPVFS. The pullout strength for PVFS
      tended to be greater than that for LMS. However, the difference was not quite
      significant (p = 0.06). CONCLUSIONS The authors introduce a novel fixation
      technique for the subaxial cervical spine. This study suggests that PVFS tend to
      provide stronger fixation than LMS for initial applications and fixation equal to
      LMS for salvage applications. If placement of LMS fails, PVFS can serve as a
      salvage fixation technique.

PMID- 28498073
TI  - Does the mesodermal derangement in Chiari Type I malformation extend to the
      cervical spine? Evidence from an analytical morphometric study on cervical
      paraspinal muscles.
AB  - OBJECTIVE The mesodermal derangement in Chiari Type I malformation (CMI) has been
      postulated to encompass the cervical spine. The objectives of this study were to
      assess the cross-sectional areas (CSAs) of cervical paraspinal muscles (PSMs) in
      patients with CMI without syringomyelia, compare them with those in non-CMI
      subjects, and evaluate their correlations with various factors. METHODS In this
      retrospective study, the CSAs of cervical PSMs in 25 patients were calculated on
      T2-weighted axial MR images and computed as ratios with respect to the
      corresponding vertebral body areas. These values and the cervical taper ratios
      were then compared with those of age- and sex-matched non-CMI subjects and
      analyzed with respect to demographic data and clinicoradiological factors.
      RESULTS Compared with the non-CMI group, the mean CSA values for the rectus
      capitis minor and all of the subaxial PSMs were lower in the study group, and
      those of the deep extensors were significantly lower (p = 0.004). The cervical
      taper ratio was found to be significantly higher in the study cohort (p =
      0.0003). A longer duration of symptoms and a steeper cervical taper ratio were
      independently associated with lower CSA values for the deep extensors (p = 0.04
      and p = 0.03, respectively). The presence of neck pain was associated with a
      lower CSA value for the deep flexors (p = 0.03). CONCLUSIONS Patients with CMI
      demonstrate alterations in their cervical paraspinal musculature even in the
      absence of coexistent syringomyelia. Their deep extensor muscles undergo
      significant atrophic changes that worsen with the duration of their symptoms.
      This could be related to a significantly steeper cervical taper ratio that their
      cervical cords are exposed to. Neck pain in these patients is related to atrophy
      of their deep flexor muscles. A steeper cervical taper ratio and alterations in
      the PSMs could be additional indicators for surgery in patients with CMI without
      syringomyelia.

PMID- 28498074
TI  - An analysis from the Quality Outcomes Database, Part 1. Disability, quality of
      life, and pain outcomes following lumbar spine surgery: predicting likely
      individual patient outcomes for shared decision-making.
AB  - OBJECTIVE Quality and outcomes registry platforms lie at the center of many
      emerging evidence-driven reform models. Specifically, clinical registry data are
      progressively informing health care decision-making. In this analysis, the
      authors used data from a national prospective outcomes registry (the Quality
      Outcomes Database) to develop a predictive model for 12-month postoperative pain,
      disability, and quality of life (QOL) in patients undergoing elective lumbar
      spine surgery. METHODS Included in this analysis were 7618 patients who had
      completed 12 months of follow-up. The authors prospectively assessed baseline and
      12-month patient-reported outcomes (PROs) via telephone interviews. The PROs
      assessed were those ascertained using the Oswestry Disability Index (ODI), EQ-5D,
      and numeric rating scale (NRS) for back pain (BP) and leg pain (LP). Variables
      analyzed for the predictive model included age, gender, body mass index, race,
      education level, history of prior surgery, smoking status, comorbid conditions,
      American Society of Anesthesiologists (ASA) score, symptom duration, indication
      for surgery, number of levels surgically treated, history of fusion surgery,
      surgical approach, receipt of workers' compensation, liability insurance,
      insurance status, and ambulatory ability. To create a predictive model, each 12
      month PRO was treated as an ordinal dependent variable and a separate
      proportional-odds ordinal logistic regression model was fitted for each PRO.
      RESULTS There was a significant improvement in all PROs (p < 0.0001) at 12 months
      following lumbar spine surgery. The most important predictors of overall
      disability, QOL, and pain outcomes following lumbar spine surgery were employment
      status, baseline NRS-BP scores, psychological distress, baseline ODI scores,
      level of education, workers' compensation status, symptom duration, race,
      baseline NRS-LP scores, ASA score, age, predominant symptom, smoking status, and
      insurance status. The prediction discrimination of the 4 separate novel
      predictive models was good, with a c-index of 0.69 for ODI, 0.69 for EQ-5D, 0.67
      for NRS-BP, and 0.64 for NRS-LP (i.e., good concordance between predicted
      outcomes and observed outcomes). CONCLUSIONS This study found that preoperative
      patient-specific factors derived from a prospective national outcomes registry
      significantly influence PRO measures of treatment effectiveness at 12 months
      after lumbar surgery. Novel predictive models constructed with these data hold
      the potential to improve surgical effectiveness and the overall value of spine
      surgery by optimizing patient selection and identifying important modifiable
      factors before a surgery even takes place. Furthermore, these models can advance
      patient-focused care when used as shared decision-making tools during
      preoperative patient counseling.

PMID- 28498075
TI  - The impact of 6-thioguanine incorporation into DNA on the function of DNA
      methyltransferase Dnmt3a.
AB  - The incorporation of chemotherapeutic agent 6-thioguanine (SG) into DNA is a
      prerequisite for its cytotoxic action. This modification of DNA impedes the
      activity of enzymes involved in DNA repair and replication. Here, using
      hemimethylated DNA substrates we demonstrated that DNA methylation by Dnmt3a-CD
      is reduced if DNA is damaged by the incorporation of SG into one or two CpG sites
      separated by nine base pairs. An increase in the number of SG substitutions did
      not enhance the effect. Dnmt3a-CD binding to either of SG-containing DNA
      substrates was not distorted. Our results suggest that SG incorporation into DNA
      may influence epigenetic regulation via DNA methylation.

PMID- 28498076
TI  - Cochlear implantation in Mondini's deformity: could the straight electrode array
      with length of 31 mm be fully inserted?
AB  - CONCLUSIONS: The straight electrode array with length of 31 mm can be fully
      inserted using round window insertion in cochlear implantation with Mondini's
      deformity. It is a safe and effective process, but also a challenging task of the
      full implantation in children with Mondini's deformity. OBJECTIVE: The aim of
      this study is to discuss whether the straight electrode array with a length of 31
      mm could be fully inserted in cochlear implantation with Mondini's deformity.
      METHODS: A chart review of 30 patients undergoing cochlear implantation with
      Mondini's deformity using the electrode array with length of 31 mm was undertaken
      from January 2012 and December 2015 in Anhui Provincial Hospital. RESULTS: Full
      insertion of the straight electrode array with length of 31 mm were performed
      successfully in all patients with Mondini's deformity using round window
      insertion. Resistance was not encountered while introducing the electrodes. Ten
      of 30 patients had cerebrospinal fluid drainage during cochlear implantation.
      Cerebrospinal fluid drainage was controlled with small pieces of temporalis
      fascia packing round window in all patients. Intra-operative neural response
      telemetry was performed in all patients, and results were good. The result of X
      ray showed proper placement of the cochlear implant electrode array. During
      surgery, no patients had experienced any immediate or delayed post-operative
      complications such as wound infection, intracranial complication, extrusion, or
      migration of the implant during an average follow-up period of 6-36 months.

PMID- 28498077
TI  - The effect of platelet-rich fibrin membrane on the repair of perforated tympanic
      membrane: an experimental study.
AB  - CONCLUSION: Platelet-rich fibrin (PRF) membrane could be used successfully in the
      repair of tympanic membrane perforation and wound healing. OBJECTIVES: To
      evaluate the effect of platelet-rich fibrin membrane in the repair of perforated
      tympanic membrane. METHODS: After otoscopic examination, a 3-mm perforation was
      made in the posterior quadrant of both tympanic membranes of 50 adult male
      Sprague-Dawley rats. Venous blood was withdrawn from the rats, then centrifuged.
      PRF was obtained in membrane form. The membrane was placed on the right tympanic
      membrane perforation. The perforations on the left side were left to
      spontaneously heal and, thus, formed the control group. Daily examinations were
      made of 20 rats and the time to healing of the tympanic membrane was recorded.
      The remaining 30 rats were separated into five groups of six, and
      histopathological examination was made. Evaluation was made in respect of the
      presence of oedema in the lamina propria, neovascularization, fibroblastic
      reaction, and inflammatory cells. RESULTS: The healing time of the tympanic
      membrane perforation was determined as mean 10.3 +/- 2.18 days in the study group
      applied with PRF and 17 +/- 2.40 days in the control group. Higher values in
      respect of fibrosis and neovascularization were obtained in the study group.

PMID- 28498078
TI  - Kinetic oscillatory stimulation of nasal mucosa in non-allergic rhinitis:
      comparison of patient self-administration and caregiver administration regarding
      pain and treatment effect. A randomized clinical trial.
AB  - CONCLUSION: Patient self-administration of the Kinetic Oscillatory Stimulation
      (KOS)-catheter was a fully acceptable alternative to insertion of the catheter by
      physician with helmet fixation, in patients with non-allergic rhinitis (NAR). The
      approaches were equivalent regarding pain. The treatment effect in the patient
      self-administration group was not inferior. OBJECTIVES: To evaluate whether self
      administration of a KOS-catheter was different compared to insertion by a
      physician, assessed with patient reported pain on a visual analogue scale (VAS).
      Also, to evaluate the difference in nasal stuffiness with the Sino-Nasal Outcome
      Test (SNOT-22) and Peak Nasal Inspiratory Flow (PNIF). METHODS: Patients with NAR
      were randomized to group 1, patient insertion of catheter and manual fixation,
      and group 2, catheter insertion by physician and fixation with a helmet. Patients
      were treated once, 10 min in each nasal cavity, and followed up 14 days later.
      RESULTS: Twenty-nine patients were included (group 1, n = 14; group 2, n = 15).
      There was no statistical significant difference in patient reported pain between
      groups. There was a decrease in nasal stuffiness after treatment in the total
      study population (n = 26, p = 0.001). In group 1 nasal stuffiness was decreased
      and in group 2 there was no change (group 1, p = 0.004; group 2, p = 0.071). No
      statistical significant change in PNIF was observed.

PMID- 28498079
TI  - Outcomes of cochlear implantation for the patients with specific genetic
      etiologies: a systematic literature review.
AB  - CONCLUSION: Most of the cases with gene mutations of intra-cochlear etiology
      showed relatively good CI outcomes. To progress toward more solid evidence-based
      CI intervention, a greater number of reports including CI outcomes for specific
      gene mutations are desired. BACKGROUND: Cochlear implantation (CI) is the most
      important and effective treatment for patients with profound sensorineural
      hearing loss. However, the outcomes of CI vary among patients. One of the reasons
      of this heterogeneous outcome for cochlear implantation is thought to be the
      heterogeneous nature of hearing loss. Indeed, genetic factors, the most common
      etiology in severe-to-profound hearing loss, might be one of the key determinants
      of outcomes for CI and electric acoustic stimulation (EAS). Patients with genetic
      causes involving an 'intra-cochlear' etiology show good CI/EAS outcomes. REVIEW:
      This review article aimed to summarize the reports on CI/EAS outcomes in patients
      with special genetic causes as well as to assist in future clinical decision
      making. Most of the cases were suspected of an intra-cochlear etiology, such as
      those with GJB2, SLC26A4, and OTOF mutations, which showed relatively good CI
      outcomes. However, there have only been a limited number of reports on patients
      with other gene mutations.

PMID- 28498080
TI  - HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma.
AB  - CONCLUSIONS: The heparin-binding epidermal growth factor-like growth factor (HB
      EGF) plays an essential role in the development and invasiveness of
      cholesteatoma. This study may help to realize the molecular mechanisms underlying
      the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug
      intervention of cholesteatoma. OBJECTIVE: To detect HB-EGF expression in human
      surgical specimens of acquired middle ear cholesteatoma and analyze its
      functional role as a regulator of epithelial keratinocytes hyperproliferation.
      METHODS: A total of 34 patients who underwent surgical treatment for middle ear
      cholesteatoma were recruited in the study. The mRNA and protein expression of HB
      EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was
      investigated by real-time quantitative reverse-transcription-polymerase chain
      reaction (RT-qPCR), immunohistochemical staining, and western blot. The
      correlation between bone resorption degree and HB-EGF expression was also
      analyzed. RESULTS: On average, compared with normal postauricular skin,
      expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly
      elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32
      fold by western blot. Positive HB-EGF immunostaining observed in the basal and
      suprabasal layers of cholesteatoma epithelium was significantly stronger than in
      normal postauricular skin. Meanwhile, an obviously positive correlation between
      HB-EGF protein expression and bone resorption degree was discovered.

PMID- 28498081
TI  - Finite element analysis of auditory characteristics in patients with middle ear
      diseases.
AB  - CONCLUSION: This study validates that a finite element model of the human
      ossicular chain and tympanic membrane can be used as an effective surgical
      assessment tool in clinics. OBJECTIVE: The present study was performed to
      investigate the application of a finite element model of ossicular chain and
      tympanic membrane for fabrication of individualized artificial ossicles. METHODS:
      Twenty patients (20 ears) who underwent surgery for middle ear disease (n = 20)
      and 10 healthy controls (10 ears) were enrolled in the hospital. Computed
      tomography (CT) and pure tone audiometry were performed before and after surgery.
      A finite element model was developed using CT scans, and correlation analysis was
      conducted between stapes displacement and surgical methods. An audiometric test
      was also performed for 14 patients before and after surgery. RESULTS: Stapes
      displacement in the healthy group (average = 3.31 * 10-5 mm) was significantly
      greater than that in the impaired group (average = 1.41 * 10-6 mm) prior to
      surgery. After surgery, the average displacement in the impaired group was 2.55 *
      10-6 mm, which represented a significant improvement. For the patients who
      underwent the audiometric test, 10 improved hearing after surgery, and stapes
      displacement increased in nine of these 10 patients.

PMID- 28498082
TI  - The Safety and Feasibility of Re-treating Patients with Severe Emphysema with
      Endobronchial Coils: A Pilot Study.
AB  - Severe emphysema patients who have been treated with endobronchial coils have
      been shown to initially benefit, but slowly decline in the years thereafter. Re
      treating a patient with endobronchial coils could potentially lead to new
      improvements and may again reduce the rate of further decline. To our knowledge,
      until now, no results are published about patients who are re-treated. The
      primary aim of this study is to investigate the safety and feasibility of re
      treating severe emphysema patients with endobronchial coils, using the PneumRx
      coil system. Furthermore, as secondary aim, we will evaluate the efficacy of re
      treating these patients. Patients who at least 2 years ago were treated with
      endobronchial coils and responded clinically meaningful to this treatment were
      included in the study and re-treated. Safety was evaluated by the number of
      reported adverse events. Efficacy was evaluated 6 months after re-treatment, and
      measured by the change in quality of life, exercise capacity and pulmonary
      function testing. Eight patients were re-treated at a median of 1382 days (range
      849-1545) after initial coil treatment with a median additional of 12 (10-15)
      coils per patient. During treatment, and until 6 months of follow-up, no
      unexpected adverse events occurred. Quality of life, exercise capacity and lung
      function did not change significantly 6 months after re-treatment. The results of
      this pilot study suggest that re-treating patients with endobronchial coils is
      feasible and safe. However, larger studies are needed to confirm these results
      and to investigate the efficacy and thus the clinical relevance.

PMID- 28498083
TI  - Computer-assisted CI fitting: Is the learning capacity of the intelligent agent
      FOX beneficial for speech understanding?
AB  - OBJECTIVE: The software application FOX ('Fitting to Outcome eXpert') is an
      intelligent agent to assist in the programing of cochlear implant (CI)
      processors. The current version utilizes a mixture of deterministic and
      probabilistic logic which is able to improve over time through a learning effect.
      This study aimed at assessing whether this learning capacity yields measurable
      improvements in speech understanding. METHODS: A retrospective study was
      performed on 25 consecutive CI recipients with a median CI use experience of 10
      years who came for their annual CI follow-up fitting session. All subjects were
      assessed by means of speech audiometry with open set monosyllables at 40, 55, 70,
      and 85 dB SPL in quiet with their home MAP. Other psychoacoustic tests were
      executed depending on the audiologist's clinical judgment. The home MAP and the
      corresponding test results were entered into FOX. If FOX suggested to make MAP
      changes, they were implemented and another speech audiometry was performed with
      the new MAP. RESULTS: FOX suggested MAP changes in 21 subjects (84%). The within
      subject comparison showed a significant median improvement of 10, 3, 1, and 7% at
      40, 55, 70, and 85 dB SPL, respectively. All but two subjects showed an
      instantaneous improvement in their mean speech audiometric score. DISCUSSION:
      Persons with long-term CI use, who received a FOX-assisted CI fitting at least 6
      months ago, display improved speech understanding after MAP modifications, as
      recommended by the current version of FOX. This can be explained only by
      intrinsic improvements in FOX's algorithms, as they have resulted from learning.
      This learning is an inherent feature of artificial intelligence and it may yield
      measurable benefit in speech understanding even in long-term CI recipients.

PMID- 28498087
TI  - An expert opinion on PANDAS/PANS: highlights and controversies.
AB  - OBJECTIVES: 'Pediatric Autoimmune Neuropsychiatric Disorders Associated with
      Streptococcal Infections' (PANDAS) identified a unique subgroup of patients with
      abrupt onset of obsessive compulsive disorder (OCD) symptoms clinically related
      to Streptococcus infection and accompanied by neuropsychological and motor
      symptoms. After almost 20 years, PANDAS has not been accepted as distinct
      disorder and new criteria for paediatric acute-onset neuropsychiatric syndrome
      (PANS) have been replaced it, highlighting the fact that several agents rather
      than only Streptococcus might be involved. METHODS: Extensive review of the
      PANDAS/PANS literature was performed on PubMed. RESULTS: Although antibiotics
      have been reported to be effective for acute and prophylactic phases in several
      uncontrolled studies and non-steroidal anti-inflammatory drugs (NSAID) are used
      during exacerbations, clinical multicenter trials are still missing. Selective
      serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) are
      still the first line of recommendation for acute onset OCD spectrum.
      Immunological therapies should be restricted to a few cases. CONCLUSIONS: While
      PANDAS has found no confirmation as a distinct syndrome, and it is not presented
      in DSM-5, patients with acute onset OCD spectrum, neurocognitive and motor
      symptoms should be evaluated for inflammatory, infective, immunological and
      metabolic abnormalities with a comprehensive diagnostic algorithm.

PMID- 28498088
TI  - Mental health problems of second generation children and adolescents with
      migration background.
AB  - OBJECTIVE: Despite the growing number of young second-generation immigrant (SGI)
      children and adolescents, studies about their mental health are rare. The
      objective of this study was to investigate the mental health problems of SGI
      children and adolescents in Istanbul, Turkey. METHODS: In a clinical sample the
      mental health of 54 SGIs and 50 native children and adolescents were examined
      using the Schedule for Affective Disorders and Schizophrenia for School Aged
      Children-Present and Lifetime Version (K-SADS-PL) and Children's Global
      Assessment Scale. The assessments were carried out by a blinded rater. RESULTS:
      SGI children had higher rates of psychiatric disorders such as depression (p =
      0.001), post-traumatic stress disorder (PTSD) (p = 0.011) and anxiety disorders
      (p = 0.013), more comorbid disorders and lower functionality scores compared to
      their native counterparts (p = 0.001). CONCLUSIONS: SGI children seem to have
      higher rates of psychiatric disorders most probably due to migration-induced
      burdens. The professionals treating SGI children should have more awareness for
      these problems to be able to approach them in a culture and language sensitive
      way.

PMID- 28498089
TI  - Changes in BMI in hospitalized patients during treatment with antipsychotics,
      depending on gender and other factors.
AB  - OBJECTIVE: To investigate the differences in body mass index (BMI) changes
      between men and women during hospitalization. METHODS: The retrospective study
      monitored demographic and clinical data of 462 schizophrenic patients
      hospitalized 737 times between 2006 and 2011. BMI analysis was performed on
      patients on antipsychotic medication hospitalized longer than four days. RESULTS:
      Patients with an initial BMI < 25 gained more weight than patients with a BMI >
      25 (3.94% vs. 0.23%, men 4.02% vs. 0.69%, women 3.79% vs. -0.52%, always p <
      0.001). Greater BMI gains were reported during the first hospitalization than
      during subsequent ones (3.94% vs. 1.66%, men 3.97% vs. 1.98%, women 3.88% vs.
      1.18%, always p < 0.001). The comparison between men and women showed a higher
      increase in BMI in men 2.36% vs. 1.54%, p = 0.022. Men also gained significantly
      more weight than women on polytherapy (+2.55% vs. +1.37%) and during subsequent
      hospitalizations (1.98% vs. 1.18%). For treatment with various atypical
      antipsychotics (AP), no significant differences were found in weight changes
      between men and women; during treatment using a combination of multi-receptor AP
      and metabolically neutral aripiprazole, a significant increase of BMI occurred in
      men, but not in women (p = 0.018). CONCLUSIONS: Men appear to be more prone to
      weight gain than women.

PMID- 28498090
TI  - World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for
      biological treatment of schizophrenia - a short version for primary care.
AB  - OBJECTIVE: Schizophrenia is a severe mental disorder and many patients are
      treated in primary care settings. Apart from the pharmacological management of
      disease-associated symptoms, the detection and treatment of side effects is of
      the utmost importance in clinical practice. The purpose of this publication is to
      offer relevant evidence-based recommendations for the biological treatment of
      schizophrenia in primary care. METHODS: This publication is a short and practice
      oriented summary of Parts I-III of the World Federation of Societies of
      Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of
      Schizophrenia. The recommendations were developed by the authors and consented by
      a task force of international experts. Guideline recommendations are based on
      randomized-controlled trials and supplemented with non-randomized trials and meta
      analyses where necessary. RESULTS: Antipsychotics of different chemical classes
      are the first-line pharmacological treatments for schizophrenia. Specific
      circumstances (e.g., suicidality, depression, substance dependence) may need
      additional treatment options. The pharmacological and non-pharmacological
      management of side effects is of crucial importance for the long-term treatment
      in all settings of the healthcare system. CONCLUSIONS: This summary of the three
      available evidence-based guidelines has the potential to support clinical
      decisions and can improve treatment of schizophrenia in primary care settings.

PMID- 28498091
TI  - Letter to the Editor. Endoscopic third ventriculostomy with choroid plexus
      cauterization.

PMID- 28498092
TI  - Barriers to ESC guideline implementation: results of a survey from the European
      Council on Cardiovascular Nursing and Allied Professions (CCNAP).
AB  - BACKGROUND: The European Society of Cardiology (ESC) has a comprehensive clinical
      guideline development programme, relevant for all clinicians. However,
      implementation of guidelines is not always optimal. AIM: The aim of this study
      was to determine nurses' and allied professionals' awareness and barriers
      regarding clinical guideline implementation. METHODS: A cross-sectional survey
      was administrated online and in print at EuroHeartCare 2015. A questionnaire was
      developed which examined awareness and barriers to implementation of ESC
      guidelines on cardiovascular disease prevention in clinical practice (2012) and
      ESC guidelines in general. RESULTS: Of the 298 respondents, 12% reported that the
      prevention guidelines were used in their practice area. Respondents identified,
      in order of magnitude, that lack of leadership, workload, time, resources and a
      perception that they were unable to influence current practice were barriers to
      the use of the prevention guidelines. When asked to rank barriers to use of any
      ESC guidelines, time (22%) and leadership (23%) were ranked highest. CONCLUSIONS:
      Implementation of ESC guidelines by nurses, the majority responders in this
      survey, is a serious problem, requiring urgent improvement to ensure patients
      receive optimal evidence based care. Issues of leadership, workload, time and
      resources are significant barriers to guideline implementation. It is of concern
      that these professionals perceive both that they have little influence on
      implementation decisions and lack of leadership regarding guideline
      implementation. Educational and organisational strategies to improve leadership
      skills are imperative. These will build self-efficacy and empower nurses and
      allied professionals to advocate for evidence-based care in the clinical
      environment.

PMID- 28498093
TI  - Cardiac tissue engineering: from matrix design to the engineering of bionic
      hearts.
AB  - The field of cardiac tissue engineering aims at replacing the scar tissue created
      after a patient has suffered from a myocardial infarction. Various technologies
      have been developed toward fabricating a functional engineered tissue that
      closely resembles that of the native heart. While the field continues to grow and
      techniques for better tissue fabrication continue to emerge, several hurdles
      still remain to be overcome. In this review we will focus on several key advances
      and recent technologies developed in the field, including biomimicking the
      natural extracellular matrix structure and enhancing the transfer of the
      electrical signal. We will also discuss recent developments in the engineering of
      bionic cardiac tissues which integrate the fields of tissue engineering and
      electronics to monitor and control tissue performance.

PMID- 28498094
TI  - Predictors of all-cause 30 day readmission among Medicare patients with type 2
      diabetes.
AB  - OBJECTIVE: Readmission is costly among patients with type 2 diabetes (T2DM) in
      Medicare Advantage Prescription Drug Plans; identifying high-risk patients is
      necessary for targeting reduction programs. The objective of this study was to
      develop a claims-based algorithm to predict all-cause 30 day readmission among
      patients with T2DM. METHODS: This study used administrative data from 1 January
      2012 through 31 January 2014. The cohort included hospitalized T2DM patients,
      aged 18-90 with >=12 months' continuous enrollment before an unplanned hospital
      admission and >=1 month of enrollment post-discharge, excluding patients in long
      term care >30 days pre-index. Multivariate logistic regression predicted the
      likelihood of readmission following hospitalization in 2013. The analytic file
      was randomly split into training and test datasets to build and validate the
      model. Candidate variables included physician and patient demographics, baseline
      clinical conditions, and healthcare utilization metrics. Clinical conditions were
      classified using the Healthcare Cost and Utilization Project clinical
      classification system for ICD-9-CM. RESULTS: Of 63,237 individuals, 17.1%
      experienced a readmission. Of nearly 200 candidate variables, 14 were predictors
      of readmission, including total cumulative number of days for inpatient stays and
      the number of emergency department visits in the baseline period. Male gender,
      older age, and certain comorbidities were associated with higher likelihood of
      readmission. The final model demonstrated good discriminant ability (c-statistic
      = 0.82). CONCLUSIONS: This study provided evidence that certain patient
      characteristics and healthcare utilization are predictive of readmission. An
      algorithm with good discriminant ability was developed which could be used to
      target readmission reduction programs. Physician gender, specialty, and ownership
      status did not appear to influence the likelihood of readmission.

PMID- 28498095
TI  - Risk factors for development of postoperative cerebellar mutism syndrome in
      children after medulloblastoma surgery.
AB  - OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of
      children after cerebellar tumor surgery. Typical features include a latent onset
      of 1-2 days after surgery, transient mutism, emotional lability, and a wide
      variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome
      usually persist long term. The principal causal factor is bilateral surgical
      damage (regardless of tumor location) to any component of the proximal efferent
      cerebellar pathway, which leads to temporary dysfunction of cerebral cortical
      regions as a result of diaschisis. Tumor type, cerebellar midline location, and
      brainstem involvement are risk factors for pCMS that have been identified
      repeatedly, but they do not explain its latent onset. Ambiguous or negative
      results for other factors, such as hydrocephalus, postoperative meningitis,
      length of vermian incision, and tumor size, have been reached. The aim of this
      study was to identify perioperative clinical, radiological, and laboratory
      factors that also increase risk for the development of pCMS. The focus was on
      factors that might explain the delayed onset of pCMS and thus might provide a
      time window for taking precautionary measures to prevent pCMS or reduce its
      severity. The study was focused specifically on children who had undergone
      surgery for medulloblastoma. METHODS In this single-center retrospective cohort
      study, the authors included 71 children with medulloblastoma, 28 of whom
      developed pCMS after primary resection. Clinical and laboratory data were
      collected prospectively and analyzed systematically. Variables were included for
      univariate and multivariate analysis. RESULTS Univariate regression analysis
      revealed 7 variables that had a significant influence on pCMS onset, namely,
      tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of
      the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and
      hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group,
      significantly more reported incidents of severe bleeding in the tumor bed during
      surgery in the pCMS group, preoperative hydrocephalus, and a mean body
      temperature rise of 0.5 degrees C in the first 4 days after surgery in the pCMS
      group. Multiple regression analysis revealed that tumor size, tumor infiltration
      into or compression of the brainstem, and higher mean body temperature in the
      first 4 postoperative days were independent and highly significant predictors for
      pCMS. CONCLUSIONS The authors confirmed earlier findings that tumor-associated
      preoperative conditions, such as a maximum tumor diameter >= 5 cm and
      infiltration into or compression of the brainstem, are associated with a higher
      risk for the development of pCMS. Most importantly, the authors found that a 0.5
      degrees C higher mean body temperature in the first 4 postoperative days
      increased the odds ratio for the development of pCMS almost 5-fold. These data
      suggest that an important focus for the prevention of pCMS in children who have
      undergone medulloblastoma surgery might be rigorous maintenance of normothermia
      as standard care after surgery.

PMID- 28498096
TI  - Characterization of the Anti-Bovine Podoplanin Monoclonal Antibody PMab-44.
AB  - A type I transmembrane sialoglycoprotein podoplanin (PDPN) is expressed in
      several normal cells, including podocytes of the kidney, type I alveolar cells of
      the lung, and lymphatic endothelial cells. We recently produced an anti-bovine
      PDPN (bovPDPN) monoclonal antibody (mAb), PMab-44, by immunizing mice with
      recombinant proteins of bovPDPN. In this study, we determined the critical
      epitope of PMab-44 for the recognition of bovPDPN using many deletion mutants and
      point mutants of bovPDPN. Flow cytometric analyses revealed that the epitope of
      PMab-44 was Glu46-Thr50, which corresponds to platelet aggregation-stimulating
      (PLAG) domain-3. The important amino acids in the PMab-44 epitope were determined
      to be Glu46, Tyr48, and Thr50. Western blot analysis also confirmed these
      results, indicating that the PLAG domain of bovPDPN is also important in
      immunogenicity for producing useful anti-PDPN mAbs.

PMID- 28498097
TI  - The Asplenic Patient: Post-Insult Immunocompetence, Infection, and Vaccination.
AB  - BACKGROUND: Splenic injury can occur through multiple mechanisms and may result
      in various degrees of residual immunocompetence. Functionally or anatomically
      asplenic patients are at higher risk for infection, particularly with
      encapsulated bacteria. Vaccination is recommended to prevent infection with these
      organisms; however, the recommendations are routinely updated, and vaccine
      selection and timing are complex. METHODS: Review of the pertinent English
      language literature, including the recommendations of the U.S. Centers for
      Disease Control and Prevention's Advisory Committee on Immunization Practices.
      RESULTS: Overwhelming post-splenectomy infection is associated with high
      morbidity and mortality rates. Patients requiring splenectomy for trauma-related
      injury appear to be at lower risk for infection than those undergoing splenectomy
      for a hematologic or oncologic indication. Initial vaccination is dependent on
      immunization history but generally should consist of the 13-valent pneumococcal
      conjugate, quadrivalent meningococcal conjugate, meningococcal serogroup B, and
      Haemophilus influenzae serotype b (Hib) vaccines. Antimicrobial prophylaxis for
      certain asplenic patients, such as children under the age of five y, may be
      indicated. CONCLUSION: Immunization remains a key measure to prevent overwhelming
      post-splenectomy infection. Consideration of new recommendations and indications,
      possible interactions, and timing remains important to including optimal response
      to the vaccines.

PMID- 28498098
TI  - Germinal center B cell development has distinctly regulated stages completed by
      disengagement from T cell help.
AB  - To reconcile conflicting reports on the role of CD40 signaling in germinal center
      (GC) formation, we examined the earliest stages of murine GC B cell
      differentiation. Peri-follicular GC precursors first expressed intermediate
      levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the
      latter known to repress Bcl6 transcription. Transition of GC precursors to the
      BCL6hi follicular state was associated with cell division, although the number of
      required cell divisions was immunogen dose dependent. Potentiating T cell help or
      CD40 signaling in these GC precursors actively repressed GC B cell maturation and
      diverted their fate towards plasmablast differentiation, whereas depletion of
      CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B
      cells is necessary to generate the immediate precursors of GC B cells, transition
      to the BCL6hi follicular state is promoted by a regional and transient diminution
      of T cell help.

PMID- 28498100
TI  - Extraordinary effects of unnatural pairings.
AB  - Engineered molecules based on human cytokines have potential uses in research and
      medicine.

PMID- 28498099
TI  - Synthekines are surrogate cytokine and growth factor agonists that compel
      signaling through non-natural receptor dimers.
AB  - Cytokine and growth-factor ligands typically signal through homo- or hetero
      dimeric cell surface receptors via Janus Kinase (JAK/TYK), or Receptor Tyrosine
      Kinase (RTK)-mediated trans-phosphorylation. However, the number of receptor
      dimer pairings occurring in nature is limited to those driven by natural ligands
      encoded within our genome. We have engineered synthethic cytokines (synthekines)
      that drive formation of cytokine receptor dimer pairings that are not formed by
      endogenous cytokines and that are not found in nature, and which activate
      distinct signaling programs. We show that a wide range of non-natural cytokine
      receptor hetero-dimers are competent to elicit a signaling output. We engineered
      synthekine ligands that assembled IL-2Rbeta/IL-4Ralpha or IL-4Ralpha/IFNAR2
      receptor heterodimers, that do not occur naturally, triggering signaling and
      functional responses distinct from those activated by the endogenous cytokines IL
      2, IL-4, and IFN. Furthermore, hybrid synthekine ligands that dimerized a
      JAK/STAT cytokine receptor with a receptor tyrosine kinase (RTK) also elicited a
      signaling response. Synthekines represent a new family of synthetic ligands with
      pre-defined receptors, but 'orphan' functions, that enable the full combinatorial
      scope of dimeric signaling receptors encoded within the human genome to be
      exploited for basic research and drug discovery.

PMID- 28498101
TI  - The evolution of gene regulation.
AB  - The gene regulation mechanisms necessary for the development of complex
      multicellular animals have been found in sponges.

PMID- 28498103
TI  - A selectivity filter at the intracellular end of the acid-sensing ion channel
      pore.
AB  - Increased extracellular proton concentrations during neurotransmission are
      converted to excitatory sodium influx by acid-sensing ion channels (ASICs). 10
      fold sodium/potassium selectivity in ASICs has long been attributed to a central
      constriction in the channel pore, but experimental verification is lacking due to
      the sensitivity of this structure to conventional manipulations. Here, we
      explored the basis for ion selectivity by incorporating unnatural amino acids
      into the channel, engineering channel stoichiometry and performing free energy
      simulations. We observed no preference for sodium at the "GAS belt" in the
      central constriction. Instead, we identified a band of glutamate and aspartate
      side chains at the lower end of the pore that enables preferential sodium
      conduction.

PMID- 28498102
TI  - Chimeric origins of ochrophytes and haptophytes revealed through an ancient
      plastid proteome.
AB  - Plastids are supported by a wide range of proteins encoded within the nucleus and
      imported from the cytoplasm. These plastid-targeted proteins may originate from
      the endosymbiont, the host, or other sources entirely. Here, we identify and
      characterise 770 plastid-targeted proteins that are conserved across the
      ochrophytes, a major group of algae including diatoms, pelagophytes and kelps,
      that possess plastids derived from red algae. We show that the ancestral
      ochrophyte plastid proteome was an evolutionary chimera, with 25% of its
      phylogenetically tractable nucleus-encoded proteins deriving from green algae. We
      additionally show that functional mixing of host and plastid proteomes, such as
      through dual-targeting, is an ancestral feature of plastid evolution. Finally, we
      detect a clear phylogenetic signal from one ochrophyte subgroup, the lineage
      containing pelagophytes and dictyochophytes, in plastid-targeted proteins from
      another major algal lineage, the haptophytes. This may represent a possible
      serial endosymbiosis event deep in eukaryotic evolutionary history.

PMID- 28498104
TI  - Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and
      coevolutionary sequence analysis.
AB  - The interaction between the Heat Shock Proteins 70 and 40 is at the core of the
      ATPase regulation of the chaperone machinery that maintains protein homeostasis.
      However, the structural details of the interaction remain elusive and contrasting
      models have been proposed for the transient Hsp70/Hsp40 complexes. Here we
      combine molecular simulations based on both coarse-grained and atomistic models
      with coevolutionary sequence analysis to shed light on this problem by focusing
      on the bacterial DnaK/DnaJ system. The integration of these complementary
      approaches resulted in a novel structural model that rationalizes previous
      experimental observations. We identify an evolutionarily conserved interaction
      surface formed by helix II of the DnaJ J-domain and a structurally contiguous
      region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter
      domain linker, and the beta-basket of the substrate binding domain.

PMID- 28498105
TI  - Intracellular uptake of macromolecules by brain lymphatic endothelial cells
      during zebrafish embryonic development.
AB  - The lymphatic system controls fluid homeostasis and the clearance of
      macromolecules from interstitial compartments. In mammals brain lymphatics were
      only recently discovered, with significant implications for physiology and
      disease. We examined zebrafish for the presence of brain lymphatics and found
      loosely connected endothelial cells with lymphatic molecular signature covering
      parts of the brain without forming endothelial tubular structures. These brain
      lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct
      from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose
      macromolecules in a selective manner, which can be blocked by injection of
      mannose receptor ligands. This first report on brain lymphatic endothelial cells
      in a vertebrate embryo identifies cells with unique features, including the
      uptake of macromolecules at a single cell level. Future studies will address
      whether this represents an uptake mechanism that is conserved in mammals and how
      these cells affect functions of the embryonic and adult brain.

PMID- 28498107
TI  - Ultrasound-assisted thrombolysis of an occluded transjugular portosystemic shunt.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) insertion is commonly
      performed for refractory ascites or variceal bleeding. However, TIPS dysfunction
      can be seen in both early and late settings, with shunt thrombosis a particular
      problem. Treatment of shunt dysfunction commonly involves angioplasty and re
      lining, with or without embolectomy, mechanical thrombectomy, or thrombolysis.
      Ultrasound-assisted thrombolysis has been shown to be successful for treatment of
      pulmonary embolism, deep vein thrombosis, and peripheral arterial
      thromboembolism, but has not been described before for TIPS occlusion. Ultrasound
      is theorized to lead to a shortened duration of thrombolysis due to thinning of
      the fibrin clot and exposing plasminogen receptor sites. In this technical
      report, we describe the first published use of ultrasound-assisted thrombolysis
      in the declotting of an occluded TIPS. We found that the use of ultrasound
      assisted thrombolysis allowed a relatively short duration of thrombolytic
      therapy, with removal of thrombus extending into the portal vein, facilitating
      stent re-lining. No complications were observed, in particular no bleeding
      complications. The TIPS remains patent at 8 months postprocedure.

PMID- 28498106
TI  - Kinetic modeling predicts a stimulatory role for ribosome collisions at
      elongation stall sites in bacteria.
AB  - Ribosome stalling on mRNAs can decrease protein expression. To decipher ribosome
      kinetics at stall sites, we induced ribosome stalling at specific codons by
      starving the bacterium Escherichia coli for the cognate amino acid. We measured
      protein synthesis rates from a reporter library of over 100 variants that encoded
      systematic perturbations of translation initiation rate, the number of stall
      sites, and the distance between stall sites. Our measurements are quantitatively
      inconsistent with two widely-used kinetic models for stalled ribosomes: ribosome
      traffic jams that block initiation, and abortive (premature) termination of
      stalled ribosomes. Rather, our measurements support a model in which collision
      with a trailing ribosome causes abortive termination of the stalled ribosome. In
      our computational analysis, ribosome collisions selectively stimulate abortive
      termination without fine-tuning of kinetic rate parameters at ribosome stall
      sites. We propose that ribosome collisions serve as a robust timer for
      translational quality control pathways to recognize stalled ribosomes.

PMID- 28498109
TI  - Ultra-stiff metallic glasses through bond energy density design.
AB  - The elastic properties of crystalline metals scale with their valence electron
      density. Similar observations have been made for metallic glasses. However, for
      metallic glasses where covalent bonding predominates, such as metalloid metallic
      glasses, this relationship appears to break down. At present, the reasons for
      this are not understood. Using high energy x-ray diffraction analysis of melt
      spun and thin film metallic glasses combined with density functional theory based
      molecular dynamics simulations, we show that the physical origin of the ultrahigh
      stiffness in both metalloid and non-metalloid metallic glasses is best understood
      in terms of the bond energy density. Using the bond energy density as novel
      materials design criterion for ultra-stiff metallic glasses, we are able to
      predict a Co33.0Ta3.5B63.5 short range ordered material by density functional
      theory based molecular dynamics simulations with a high bond energy density of
      0.94 eV A-3 and a bulk modulus of 263 GPa, which is 17% greater than the stiffest
      Co-B based metallic glasses reported in literature.

PMID- 28498108
TI  - Imaging for abdominal involvement in amyloidosis.
AB  - Involvement of the abdominal organs has variable presentations mostly without
      specific findings. The objective of this pictorial essay was to illustrate the
      computed tomography and magnetic resonance imaging (MRI) findings of abdominal
      involvement in systemic amyloidosis. Heterogeneous appearance of the liver,
      periportal involvement, diffuse low signal intensity of spleen on T2-weighted
      MRI, and thickened bowel wall may be helpful imaging findings when accompanied by
      presence or history of chronic inflammatory disease and clinical suspicion for
      amyloidosis.

PMID- 28498110
TI  - Solution synthesis of lead seeded germanium nanowires and branched nanowire
      networks and their application as Li-ion battery anodes.
AB  - Herein, we report the high density growth of lead seeded germanium nanowires
      (NWs) and their development into branched nanowire networks suitable for
      application as lithium ion battery anodes. The synthesis of the NWs from lead
      seeds occurs simultaneously in both the liquid zone (solution-liquid-solid (SLS)
      growth) and solvent rich vapor zone (vapor-liquid-solid (VLS) growth) of a high
      boiling point solvent growth system. The reaction is sufficiently versatile to
      allow for the growth of NWs directly from either an evaporated catalyst layer or
      from pre-defined nanoparticle seeds and can be extended to allowing extensive
      branched nanowire formation in a secondary reaction where these seeds are coated
      onto existing wires. The NWs are characterized using TEM, SEM, XRD and DF-STEM.
      Electrochemical analysis was carried out on both the single crystal Pb-Ge NWs and
      the branched Pb-Ge NWs to assess their suitability for use as anodes in a Li-ion
      battery. Differential capacity plots show both the germanium wires and the lead
      seeds cycle lithium and contribute to the specific capacity that is approximately
      900 mAh g-1 for the single crystal wires, rising to approximately 1100 mAh g-1
      for the branched nanowire networks.

PMID- 28498111
TI  - 55Mn NMR observation of colossal magnetoresistance effect in Sm0.55Sr0.45MnO3.
AB  - Temperature dependent 55Mn NMR study of Sm0.55Sr0.45MnO3 is reported. Previous
      bulk magnetization measurements have shown that below T C ~ 125 K the sample is
      ferromagnetic metallic (FMM) and above TC it is charge ordered and insulating. In
      present report, we show that from zero-field NMR a single line double-exchange
      (DE) signal is observed at temperatures up to 139 K, which is due to a presence
      of FMM clusters also above T C. The intensity of the DE line follows the
      temperature dependence of the magnetization measured at 0.01 T. When a magnetic
      field up to 2 T is applied at 139 K (i.e. 14 K above T C), a strong increase in
      NMR intensity of the DE line is observed indicating that content of FMM regions
      increases. This reveals that metallicity is induced in the material by the
      applied magnetic field and explains the observed colossal magnetoresistance (CMR)
      effect at the microscopic level. The observation agrees with previous results,
      which confirm that the percolation of the FMM clusters is responsible for the CMR
      effect. The shift of the resonant frequency in the applied field is three times
      smaller compared to decrease expected from gyromagnetic ratio, which indicates an
      antiferromagnetic coupling between the FMM clusters.

PMID- 28498112
TI  - Effect of baffles on the hydraulic performance of sediment retention ponds.
AB  - An investigation of the effect of baffles on retention pond performance using a
      physical model of an existing sediment retention pond is presented. Analysis of
      residence time (RTD curves) was used to compare the hydraulic performance of
      different arrangements of baffles in the pond. Five different arrangements for
      the design of baffles were studied. The results show that placing a single baffle
      to deflect the influent to a sediment retention pond does not improve pond
      performance; rather, it stimulates short-circuiting. This is contradictory to the
      literature and is considered to be a consequence of the model pond incorporating
      sloping walls, which is a novel aspect of this study. Most of the previous
      studies have neglected the effects of battered walls. Conversely, the inclusion
      of more than two baffles was found to increase the hydraulic performance. The
      results reported here are limited to small and narrow ponds where a large portion
      of the pond is batter (i.e. made up of sloping walls). For large area ponds,
      batter effects may be negligible and are likely to be different from those
      reported here.

PMID- 28498113
TI  - A greenhouse gas source of surprising significance: anthropogenic CO2 emissions
      from use of methanol in sewage treatment.
AB  - The impact of methanol (CH3OH) as a source of anthropogenic carbon dioxide (CO2)
      in denitrification at wastewater treatment plants (WWTPs) has never been
      quantified. CH3OH is the most commonly purchased carbon source for sewage
      denitrification. Until recently, greenhouse gas (GHG) reporting protocols
      consistently ignored the liberation of anthropogenic CO2 attributable to CH3OH.
      This oversight can likely be attributed to a simplifying notion that CO2 produced
      through activated-sludge-process respiration is biogenic because most raw-sewage
      carbon is un-sequestered prior to entering a WWTP. Instead, a biogenic
      categorization cannot apply to fossil-fuel-derived carbon sources like CH3OH.
      This paper provides a summary of how CH3OH use at DC Water's Blue Plains Advanced
      Wastewater Treatment Plant (AWTP; Washington, DC, USA) amounts to 60 to 85% of
      the AWTP's Scope-1 emissions. The United States Environmental Protection Agency
      and Water Environment Federation databases suggest that CH3OH CO2 likely
      represents one quarter of all Scope-1 GHG emissions attributable to sewage
      treatment in the USA. Finally, many alternatives to CH3OH use exist and are
      discussed.

PMID- 28498114
TI  - Life cycle assessment of sludge management with phosphorus utilisation and
      improved hygienisation in Sweden.
AB  - To provide input to sewage sludge management strategies that address expected new
      regulations in terms of hygienisation and phosphorus recovery in Sweden, an
      environmental life cycle assessment (LCA) was made. The LCA identified
      environmental hot spots for methods that may permit sludge or phosphorus from
      sludge to be applied on agricultural land. In particular, thermophilic digestion,
      pasteurisation, thermal hydrolysis, urea treatment and mono-incineration with
      phosphorus recovery were compared. In addition, a sludge management system
      involving drying of sludge before use in forestry was investigated. The results
      showed that some major impacts are related to large uncertainties, such as those
      related to emissions from sludge storage. It also showed that large gains can be
      achieved when products from the systems replace other products, in particular
      when biogas is used to replace natural gas in vehicles, but also when sludge is
      used in agriculture and forestry. In general, there are small differences between
      the sludge management methods. Retaining the sludge matrix to allow for its
      utilisation in agriculture may conflict with keeping emissions to air and water
      from the sludge matrix low. It is recommended that any sludge management option
      minimises emissions from sludge to air and water and that resources are recovered
      and used, in line with the principles of a circular economy.

PMID- 28498115
TI  - Field campaign on sediment transport behaviour in a pressure main from pumping
      station to wastewater treatment plant in Berlin.
AB  - As part of the project KURAS, the Berliner Wasserbetriebe realized a field
      campaign in 2015 in order to increase the process knowledge regarding the
      behaviour of transported sediment in the pressure main leading from the
      pumpstation to the wastewater treatment plant. The field campaign was conducted
      because of a lack of knowledge about the general condition of the pressure main
      due to its bad accessibility and the suspicion of deposits caused by hydraulic
      underload. The practical evidence of the sediment transport performance of this
      part of the sewer system, dependent on different load cases, should present a
      basis for further analysis, for example regarding flushing measures. A positive
      side-effect of the investigation was the description of the amount of pollutants
      caused by different weather conditions in combined sewer systems and the
      alterations of the sewage composition due to biogenic processes during transport.
      The concept included the parallel sampling of the inflow at the pumpstation and
      the outflow at the end of the pressure main during different weather conditions.
      By calculating the inflow to the pressure main, as well as its outflow at
      different flow conditions, it was possible to draw conclusions in regard to the
      transport behaviour of sediment and the bioprocesses within an 8.5 km section of
      the pressure main. The results show clearly that the effects of sedimentation and
      remobilization depend on the flow conditions. The balance of the total suspended
      solids (TSS) load during daily variations in dry weather shows that the
      remobilization effect during the run-off peak is not able to compensate for the
      period of sedimentation happening during the low flow at night. Based on the data
      for dry weather, an average of 238 kg of TSS deposits in the pressure main
      remains per day. The remobilization of sediment occurs only due to the abruptly
      increased delivery rates caused by precipitation events. These high pollution
      loads lead to a sudden strain at the wastewater treatment plant. It was found
      that the sediment transport behaviour is characterized by sedimentation up to a
      flow velocity of 0.35 m/s, while remobilization effects occur above 0.5 m/s. The
      assumption of bad sediment transport performance in the pressure main was
      confirmed. Therefore, the results can be used as a basis for further analysis,
      for example regarding periodical flushing as a means of cleaning the pressure
      main. The findings, especially regarding the methods and processes, are
      transferable and can be applied to other pressure mains in combined sewer
      systems. Besides the outlined evaluation of the sediment transport behaviour of
      the pressure main, the collected data were used in the project to calibrate a
      sewer system model, including a water quality model for the catchment area, and
      as a contribution towards an early physically based sediment transport modelling
      in InfoWorks CS.

PMID- 28498116
TI  - Preparation of crosslinked chitosan magnetic membrane for cations sorption from
      aqueous solution.
AB  - A chitosan magnetic membrane was prepared in order to confer magnetic properties
      to the membrane, which could be used for the removal of cations from aqueous
      solution. The crosslinked magnetic membrane was compared with pristine chitosan
      membrane in term of stability, morphology and cation adsorption capacity. The
      fabricated magnetic materials are thermally stable as shown by thermogravimetric
      curves. The membrane containing nickel magnetic particles (CHNiF-G) shows high
      thermal stability compared to the other membranes. The Fourier transform infrared
      spectroscopy showed successful preparation of chitosan magnetic membrane.
      Scanning electron microscopy micrographs showed the rough surface of the membrane
      with increased porosity. The prepared chitosan membranes were applied to cations
      of copper, nickel and lead in dilute aqueous solution. The chitosan membrane
      showed the following adsorption order for metallic cations: Cu2+ > Ni2+ > Pb2+,
      while CHNiF-G showed higher capacity, 3.51 mmol g-1 for copper, reflecting the
      improvement in adsorption capacity, since the amount of copper on pristine
      chitosan gave 1.40 mmol g-1. The time required for adsorption to reach to the
      equilibrium was 6 h for the selected cations using different chitosan membranes.
      The kinetic study showed that adsorption followed pseudo-second order kinetics.
      The most commonly used isotherm models, Freundlich, Langmuir and Temkin, were
      applied to experimental data using linear regression technique. However, The
      Temkin model fits better to experimental data.

PMID- 28498117
TI  - Application of response surface methodology to optimize the fabrication of ZnCl2
      activated carbon from sugarcane bagasse for the removal of Cu2.
AB  - The present study focused on the application of response surface methodology to
      optimize the fabrication of activated carbon (AC) from sugarcane bagasse for
      adsorption of Cu2+ ion. The AC was synthesized via chemical activation with ZnCl2
      as the activating agent. The central composite design based experiments were
      performed to assess the individual and interactive effect of influential
      parameters, including activation temperature, ZnCl2 impregnation ratio and
      activation time on the AC yield and removal of Cu2+ ion from the aqueous
      environment. The statistically significant, well-fitting quadratic regression
      models were successfully developed as confirmed by high F- and low P-values
      (<0.0001), high correlation coefficients and lack-of-fit tests. Accordingly, the
      optimum AC yield and removal efficiency of Cu2+ were predicted, respectively, as
      48.8% and 92.7% which were approximate to the actual values. By applying the
      predicted optimal parameters, the AC shows a surprisingly high surface area of
      around 1,500 m2/g accompanied by large pore volume and narrow micropore size at
      low fabrication temperature.

PMID- 28498118
TI  - Particle separation from road runoff by a decentralised lamella system -
      laboratory tests and experiences in the field.
AB  - A new decentralised settling system based on the principle of lamella separation
      was developed for the treatment of road runoff. Two different laboratory test
      methods, the DIBt (Deutsches Institut fur Bautechnik) procedure and our own
      approach, were applied in order to evaluate the efficiency of the system based on
      the separation of fine mineral particles and a mixture of mineral and organic
      particles, respectively. Overall efficiencies (88% after DIBt and 61% according
      to our own method) were comparable to results obtained for commercial systems.
      The lamella system was then applied in the field for 1 year to treat runoff from
      a road area of 420 m2. The amount of solids separated that was calculated from a
      mass balance (10.1 kg) was consistent with the amount of sediments measured (8.6
      kg). However, the average separation efficiency was only 30% in the field study.
      This is related to the size and composition of the particles in runoff, which are
      not represented well by the material used for the test procedures. It is
      concluded that the test methods should be improved, and that more field studies
      are needed in order to obtain a better understanding of the settling behaviour of
      particles in road runoff.

PMID- 28498119
TI  - Modeling of chromium (VI) adsorption from aqueous solutions using Jordanian
      Zeolitic Tuff.
AB  - The probable use of Jordanian natural zeolitic tuff in wastewater treatment as
      natural adsorbent for the removal of Cr (VI) ions from aqueous solution in
      continuous fixed bed columns was tested experimentally and theoretically. The
      tested zeolitic tuff was obtained from Al Hala volcano (HZ) located in southern
      part of Jordan and subjected to crushing and sieving only without any further
      treatment. Experimentally the HZ grains were packed in a fixed bed column. The
      used grain sizes are HZ1 (1.0-0.60 mm) and HZ2 (0.60-0.30 mm). The adsorption
      capacity was evaluated using breakthrough curves and by applying the Thomas and
      Yoon and Nelson models. The Thomas model analysis of the measured breakthrough
      curves revealed that the adsorbent HZ2 has a higher adsorption capacity to Cr
      (VI) ions (56.3 mg/g) than HZ1 (35.5 mg/g). The time elapsed to reach 50%
      breakthrough was determined by the Yoon and Nelson model. The time to reach 50%
      breakthrough is 318.78 min and 368.18 min for HZ1 and HZ2, respectively. The
      research results indicate that the small size fraction (HZ2) is more suitable and
      effective as adsorbent material than the size fraction (HZ1) due to its high
      surface area.

PMID- 28498120
TI  - Evaluation of statistical distributions to analyze the pollution of Cd and Pb in
      urban runoff.
AB  - Heavy metal pollution in urban runoff causes severe environmental damage.
      Identification of these pollutants and their statistical analysis is necessary to
      provide management guidelines. In this study, 45 continuous probability
      distribution functions were selected to fit the Cd and Pb data in the runoff
      events of an urban area during October 2014-May 2015. The sampling was conducted
      from the outlet of the city basin during seven precipitation events. For
      evaluation and ranking of the functions, we used the goodness of fit Kolmogorov
      Smirnov and Anderson-Darling tests. The results of Cd analysis showed that
      Hyperbolic Secant, Wakeby and Log-Pearson 3 are suitable for frequency analysis
      of the event mean concentration (EMC), the instantaneous concentration series
      (ICS) and instantaneous concentration of each event (ICEE), respectively. In
      addition, the LP3, Wakeby and Generalized Extreme Value functions were chosen for
      the EMC, ICS and ICEE related to Pb contamination.

PMID- 28498121
TI  - Studies of selective adsorption, desorption and reuse of chemically altered
      biomass produced from aquatic macrophytes for treatment of metal-containing
      wastewater.
AB  - The aquatic macrophytes Salvinia sp. and Pistia stratiotes have a natural
      capacity to adsorb various elements, including heavy metals. This capacity was
      enhanced with a chemical treatment using NaOH alkaline solution for Salvinia sp.
      and a mixture of both Salvinia sp. and Pistia stratiotes at a proportion of 1:1,
      whose respective biosorbents were called SSOH and MBOH. Adsorption tests were
      done in a ternary system containing the metals copper, lead and manganese; the
      parameters considered were: starting concentration, kinetics, pH and temperature.
      The adsorption isotherms for SSOH had a maximum adsorptive capacity of 50.20,
      53.85 and 14.68 mg g-1 for Cu, Pb and Mn, respectively; for MBOH, maximum values
      were 44.62, 35.17 and 15.74 mg g-1 for Cu, Pb and Mn, respectively. The metals
      displayed different behaviors with pH variation. The results also showed an
      adsorption preference of Cu > Pb > Mn for SSOH. Desorption and readsorption
      studies were also carried out, showing 100% desorption and increased adsorption
      capacity in readsorption tests. Surface area and porosity analysis with the
      Brunauer-Emmett-Teller (BET) method indicate that after chemical modification,
      MBOH and SSOH biomasses had their surface increased in comparison to SS, with
      values of 165.5657 (MBOH), 157.4392 (SSOH) and 78.9432 m2 g-1 (SS).

PMID- 28498122
TI  - Optimization of adsorption process parameters by response surface methodology for
      hexavalent chromium removal from aqueous solutions using Annona reticulata Linn
      peel microparticles.
AB  - Fruit peel microparticles of Annona reticulata Linn were used as biosorbent for
      the sequestration of hexavalent chromium (CR(VI)). Characterization of the
      biosorbent was done using scanning electron microscopy-energy dispersive X-ray
      spectroscopy (SEM-EDXS), Fourier transfer infrared spectroscopy (FTIR), gas
      chromatography-mass spectrometry (GCMS), carbon, hydrogen, nitrogen and sulphur
      (CHNS) elemental analysis, mercury intrusion porosimetry and point of zero
      charge. Influential parameters were optimized using response surface methodology
      (RSM) with a total of 17 experimental runs based on the Box-Behnken design and
      found to be pH 1.0, temperature 25  degrees C and 100 mg/L initial chromium
      concentration. pH and concentration were found to be more influential than
      temperature. The analysis of variance indicated that a second-order polynomial
      regression equation was the most suitable for fitting the experimental data. The
      experimental runs showed a good correlation with the predicted responses (R2 =
      0.9956). The biosorption process fitted well with the Langmuir isotherm with an
      adsorption capacity of 108. 32 mg/g out of the other isotherms such as Freundlich
      and Dubinin-Radushkevich that were analyzed. Non linear pseudo first order,
      pseudo second order, and intraparticle diffusion kinetics were applied to
      describe the interaction between the biosorbent and Cr(VI). Desorption and
      regeneration performances showed that fruit peels of Annona reticulata Linn can
      be an environmental friendly option for hexavalent chromium removal from aqueous
      solutions.

PMID- 28498123
TI  - Comparison of phosphorus fraction distribution and influencing factors of
      suspended and surface sediments in the Tiaoxi watershed, China.
AB  - Suspended and surface sediments from the Tiaoxi watershed, fed by the Xitiaoxi
      and Dongtiaoxi rivers, were analyzed for total phosphorus (TP) and the inorganic
      P fractions of loosely adsorbed P that were extractable with NH4Cl (NH4Cl-P),
      reductant P (BD-P), metal oxide-bound P extractable with NaOH (NaOH-P), and
      calcium-bound, HCl-extractable P (HCl-P), while other physicochemical
      compositions were also determined. The spatial variations of P fractions in these
      sediments were investigated, and the major factors influencing the various
      fractions were explored by multivariate statistics. Compared to surface
      sediments, suspended sediments contained considerably higher concentrations of
      total nitrogen, TP, organic matter, Al, Fe, Mn and biologically available P (BAP,
      given as NH4Cl-P, BD-P and NaOH-P combined) and lower concentrations of Si, Ca
      and HCl-P in the studied catchments. Dongtiaoxi sediments had higher TP,
      inorganic phosphorus and HCl-P concentrations and a lower BAP content compared
      with Xitiaoxi sediments, trends that were associated with local geological
      backgrounds, landscapes and anthropogenic characteristics. The results of
      principal component analysis showed different effects of sediment properties on P
      fraction distributions for Xitiaoxi and Dongtiaoxi sediments. The sediment
      components and structure exert a strong influence on BAP in Xitiaoxi sediments,
      in contrast to Dongtiaoxi sediments, where P fractions are mainly affected by
      urbanization and other anthropogenic activities such as shipping.

PMID- 28498124
TI  - Treatment and potential reuse of greywater from schools: a pilot study.
AB  - This study presented performance data on a low cost and easy maintenance pilot
      system for on-site treatment and reuse of water collected from wash sinks and
      fountains, as major sources of greywater (GW) at schools. Various treatment
      options were studied including screening, sand filtration, chlorination, and UV
      disinfection operated at different flow rates. Results showed that filtration
      operated at low rates is very effective in total suspended solids (TSS) removal,
      while UV proved to be more effective than chlorination for reduction of
      biochemical oxygen demand (BOD), chemical oxygen demand (COD), and total
      coliforms. Removal efficiencies up to 63%, 30% and 20% were obtained for TSS, COD
      and BOD, respectively and reductions of log TC (CFU/100 ml) from 6.5 to 2 were
      obtained at a filtration rate of 14 m3/d.m2. Treated effluent satisfied WHO
      standards for reclaimed water reuse in landscape irrigation and toilet flushing.
      The filtration-UV system is robust, showing the best and most reliable
      performance for low and high strength GW treatment even under a 10-fold increase
      in flow rate. A 5 m3/d pilot plant was developed for schools having 500 students
      and detailed cost-benefit analysis indicated a net saving value, a surplus of
      $1,600 per year, and pay back after 6 years and 11 months.

PMID- 28498125
TI  - Examining the effects of urban agglomeration polders on flood events in Qinhuai
      River basin, China with HEC-HMS model.
AB  - The urban agglomeration polders type of flood control pattern is a general flood
      control pattern in the eastern plain area and some of the secondary river basins
      in China. A HEC-HMS model of Qinhuai River basin based on the flood control
      pattern was established for simulating basin runoff, examining the impact of
      urban agglomeration polders on flood events, and estimating the effects of
      urbanization on hydrological processes of the urban agglomeration polders in
      Qinhuai River basin. The results indicate that the urban agglomeration polders
      could increase the peak flow and flood volume. The smaller the scale of the
      flood, the more significant the influence of the polder was to the flood volume.
      The distribution of the city circle polder has no obvious impact on the flood
      volume, but has effect on the peak flow. The closer the polder is to basin
      output, the smaller the influence it has on peak flows. As the level of
      urbanization gradually improving of city circle polder, flood volumes and peak
      flows gradually increase compared to those with the current level of urbanization
      (the impervious rate was 20%). The potential change in flood volume and peak flow
      with increasing impervious rate shows a linear relationship.

PMID- 28498126
TI  - Modelling energy costs for different operational strategies of a large water
      resource recovery facility.
AB  - The main objective of this paper is to demonstrate the importance of applying
      dynamic modelling and real energy prices on a full scale water resource recovery
      facility (WRRF) for the evaluation of control strategies in terms of energy costs
      with aeration. The Activated Sludge Model No. 1 (ASM1) was coupled with real
      energy pricing and a power consumption model and applied as a dynamic simulation
      case study. The model calibration is based on the STOWA protocol. The case study
      investigates the importance of providing real energy pricing comparing (i) real
      energy pricing, (ii) weighted arithmetic mean energy pricing and (iii) arithmetic
      mean energy pricing. The operational strategies evaluated were (i) old versus new
      air diffusers, (ii) different DO set-points and (iii) implementation of a carbon
      removal controller based on nitrate sensor readings. The application in a full
      scale WRRF of the ASM1 model coupled with real energy costs was successful.
      Dynamic modelling with real energy pricing instead of constant energy pricing
      enables the wastewater utility to optimize energy consumption according to the
      real energy price structure. Specific energy cost allows the identification of
      time periods with potential for linking WRRF with the electric grid to optimize
      the treatment costs, satisfying operational goals.

PMID- 28498127
TI  - Accelerated anaerobic release of K, Mg and P from surplus activated sludge for
      element recovery and struvite formation inhibition.
AB  - Accelerated release of potassium (K), magnesium (Mg) and phosphorus (P) from
      surplus activated sludge (SAS) was investigated to develop a new system for the
      recovery of the elements. Anaerobic cultivation of SAS during 24 h released 78%
      of K and about 50% of Mg and P from SAS more effectively compared to aerobic
      cultivation (K: 40%, Mg: 15%, P: 15%). Furthermore, the addition of sodium
      acetate as an organic carbon source remarkably accelerated the release of K, Mg
      and P from SAS under anaerobic condition. However, no increase in the maximum
      release efficiencies was observed. The elements released from SAS could be
      transferred to separate liquid with the existing mechanical thickener and be
      recovered as MgKPO4 by some additional process. Furthermore, the removal of the
      elements from SAS would inhibit the formation of struvite causing the blockage of
      sludge transport pipe after anaerobic digestion process of thickened sludge.

PMID- 28498128
TI  - Multi-parameter based coagulant dosing control.
AB  - The required coagulant dosage is strongly related to the quality of raw water or
      wastewater. Online sensors for most quality parameters are now readily available
      to treatment facilities, yet remain rarely used in treatment process control.
      This paper presents the evaluation of an advanced coagulant dosing control system
      based on online measurements in full-scale processes. The popular multivariate
      analytical method, partial least square regression, was used to build up the
      relationship between the coagulant dose and wastewater quality. The system was
      tested in two wastewater treatment plants (WWTPs) in Norway. Coagulant savings up
      to 30% in Norwegian plants were observed with feed forward calibrations. The
      considerable savings reduce sludge production, leading to further cost saving on
      sludge treatment. This paper presents the method, function and experiences of the
      full-scale implementation of the system in different WWTPs.

PMID- 28498129
TI  - Photodegradation of diclofenac in aqueous solution by simulated sunlight
      irradiation: kinetics, thermodynamics and pathways.
AB  - Diclofenac (DCF) is one of the most frequently detected pharmaceuticals in
      various water samples. This paper studied the effects of aquatic environmental
      factors (pH, temperature and dissolved organic matter) on photodegradation of DCF
      under simulated sunlight. The results demonstrate that degradation pathways
      proceed via pseudo first-order kinetics in all cases and the photodegradation of
      DCF by simulated sunlight. Thermodynamic study indicated that the
      photodegradation course is spontaneous, exothermic and irreversible. The rate
      constant gradually increased when the pH increased from 3 to 5, then decreased
      when the pH increased from 5 to 8, and finally increased when the pH further
      increased from 8 to 12. Humic acid inhibited the photodegradation of DCF. Three
      kinds of main degradation products were observed by high performance liquid
      chromatography/mass spectrometry and the degradation pathways were suggested. A
      toxicity test using Photobacterium phosphoreum T3 Sp indicated the generation of
      some more toxic products than DCF.

PMID- 28498130
TI  - Comparison of in situ DGT measurement with ex situ methods for predicting cadmium
      bioavailability in soils with combined pollution to biotas.
AB  - To assess the capabilities of the different techniques in predicting Cadmium (Cd)
      bioavailability in Cd-contaminated soils with the addition of Zn, one in situ
      technique (diffusive gradients in thin films; DGT) was compared with soil
      solution concentration and four widely used single-step extraction methods
      (acetic acid, EDTA, sodium acetate and CaCl2). Wheat and maize were selected as
      tested species. The results demonstrated that single Cd-polluted soils inhibited
      the growth of wheat and maize significantly compared with control plants; the
      shoot and root biomasses of the plants both dropped significantly (P < 0.05). The
      addition of Zn exhibited a strong antagonism to the physiological toxicity
      induced by Cd. The Pearson correlation coefficient presented positive
      correlations (P < 0.01, R > 0.9) between Cd concentrations in two plants and Cd
      bioavailability indicated by each method in soils. Consequently, the results
      indicated that the DGT technique could be regarded as a good predictor of Cd
      bioavailability to plants, comparable to soil solution concentration and the four
      single-step extraction methods. Because the DGT technique can offer in situ data,
      it is expected to be widely used in more areas.

PMID- 28498131
TI  - Pre-treatment of thickened waste activated sludge (TWAS) for enhanced biogas
      production via the application of a novel radial horn sonication technology.
AB  - The efficacy of sonication as a pre-treatment to anaerobic digestion (AD) was
      assessed using thickened waste activated sludge (TWAS). Efficiency was measured
      in relation to solubilisation, dewaterability, and AD performance. Eighteen
      experimental conditions were evaluated at low frequency (20 kHz), duration (2-10
      s), amplitude (~8-12 MUm) and applied pressure (0.5-3.0 barg), using a sonixTM
      patented titanium sonoprobe capable of delivering an instantaneous power of ~6 kW
      provided by Doosan Enpure Ltd (DEL). An optimised experimental protocol was used
      as a pre-treatment for biochemical methane potential (BMP) testing and semi
      continuous trials. Four digesters, with a 2-L working volume were operated
      mesophilically (37 +/- 0.5  degrees C) over 22 days. The results showed that the
      sonixTM technology delivers effective sonication at very short retention times
      compared to conventional system. Results demonstrate that the technology
      effectively disrupts the floc structures and filaments within the TWAS, causing
      an increase in solubilisation and fine readily digestible material. Both BMP
      tests and semi-continuous trials demonstrated that sonicated TWAS gave higher
      biodegradability and methane potential compared to untreated TWAS. Partial-stream
      sonication (30:70 sonicated to untreated TWAS) resulted in a proportionate
      increase in biogas production illustrating the benefits of full-stream
      sonication.

PMID- 28498132
TI  - Nitrate adsorption from aqueous solutions by calcined ternary Mg-Al-Fe
      hydrotalcite.
AB  - Calcined ternary hydrotalcite like compounds had been synthesized by co
      precipitation and calcined at 450  degrees C for 6 h. It had been applied into
      the nitrate removal from aqueous solutions. Various factors during adsorption
      process, such as chemical composition of adsorbents, adsorbent dosage, initial
      concentration of nitrate, initial pH and co-existing anions on nitrate adsorption
      had been investigated. It was found that 1.5 g/L CHTlcs (Mg/Al/Fe molar ratio =
      3:0.1:0.9) could achieve ideal adsorption efficiency at an initial nitrate
      concentration of 100 mg/L. The value of pH had little effect on nitrate
      adsorption. The co-existing anions had the inhibitory effect on nitrate
      adsorption, which was in the order of PO43- > SO42- > Cl- > ClO4-. The batch
      adsorption studies showed that experimental data were well described by the
      pseudo-second-order kinetic model and Langmuir isotherm model, and the maximum
      isotherm adsorption capacity was 123.305 mg/g. The adsorption of nitrate was a
      spontaneous exothermic process with the reduction of entropy. The proposed
      adsorption mechanism obtained from characterization was that CHTlcs uptake
      nitrate through reconstruction effect and adsorption on external surface.

PMID- 28498133
TI  - Numerical and experimental study of the fundamental flow characteristics of a 3D
      gully box under drainage.
AB  - Numerical studies regarding the influence of entrapped air on the hydraulic
      performance of gullies are nonexistent. This is due to the lack of a model that
      simulates the air-entrainment phenomena and consequently the entrapped air. In
      this work, we used experimental data to validate an air-entrainment model that
      uses a Volume-of-Fluid based method to detect the interface and the Shear-stress
      transport k-omega turbulence model. The air is detected in a sub-grid scale,
      generated by a source term and transported using a slip velocity formulation.
      Results are shown in terms of free-surface elevation, velocity profiles,
      turbulent kinetic energy and discharge coefficients. The air-entrainment model
      allied to the turbulence model showed a good accuracy in the prediction of the
      zones of the gully where the air is more concentrated.

PMID- 28498134
TI  - Nanoscale Fe/Ag particles activated persulfate: optimization using response
      surface methodology.
AB  - This work studied the bimetallic nanoparticles Fe-Ag (nZVI-Ag) activated
      persulfate (PS) in aqueous solution using response surface methodology. The Box
      Behnken design (BBD) was employed to optimize three parameters (nZVI-Ag dose,
      reaction temperature, and PS concentration) using 4-chlorophenol (4-CP) as the
      target pollutant. The synthesis of nZVI-Ag particles was carried out through a
      reduction of FeCl2 with NaBH4 followed by reductive deposition of Ag. The
      catalyst was characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and Brunauer-Emmett-Teller (BET) surface area. The BBD was
      considered a satisfactory model to optimize the process. Confirmatory tests were
      carried out using predicted and experimental values under the optimal conditions
      (50 mg L-1 nZVI-Ag, 21 mM PS at 57  degrees C) and the complete removal of 4-CP
      achieved experimentally was successfully predicted by the model, whereas the
      mineralization degree predicted (90%) was slightly overestimated against the
      measured data (83%).

PMID- 28498135
TI  - Removal of toxic Congo red dye from water employing low-cost coconut residual
      fiber.
AB  - The coconut residual fiber (CRF) is the major byproduct obtained during
      production of virgin coconut oil. Its application as a biosorbent for adsorption
      of Congo red was investigated. The CRF was subjected to different pretreatments,
      namely, pressure cooking, hexane treatment, acid treatment and their
      combinations. The pretreatment of CRF with the combination of hexane, acid, and
      pressure cooking resulted in the highest degree of adsorption. The equilibrium
      data were analyzed and found to fit best to both Langmuir and Freundlich
      isotherms. Thermodynamic parameters such as standard free energy (DeltaG0 kJ mol
      1), standard enthalpy (DeltaH0, kJ mol-1) and standard entropy (DeltaS0, kJ mol-1
      K-1) of the systems were calculated by using the Langmuir constant. The DeltaG0,
      DeltaH0 and DeltaS0 were found to be 16.51 kJ mol-1, -19.39 kJ mol-1 and -0.12 kJ
      mol-1 K-1, respectively, at 300 K. These thermodynamic parameters suggest the
      present adsorption process to be non-spontaneous and exothermic. The adsorption
      process was observed to follow pseudo-second-order kinetics. The results suggest
      that CRF has potential to be a biosorbent for the removal of hazardous material
      (Congo red dye) with a maximum adsorption capacity of 128.94 mg g-1 at 300 K.

PMID- 28498136
TI  - Gunshot Wound in an 18-Year-Old Woman, Inflicted With a Hunting Weapon Through an
      Obstacle (Mobile Phone): Reconstruction of Events.
AB  - The article presents a case of an 18-year-old woman wounded by a shot fired from
      a distance with a hunting weapon. Because the location of the entrance and exit
      wounds initially seemed inconsistent with the reports (both wounds were described
      as "large and irregular in shape") and no photographs documenting the inflicted
      injuries were taken, the case was referred for an opinion to the Department of
      Forensic Medicine in Lodz. After a review of the medical records, radiology, the
      victim's clothing, and performance of an experiment using the gun and ammunition,
      it was established that the entrance wound was located on the abdomen, and the
      exit wound was located on the buttock. The initial problems with recognizing the
      entrance and exit wounds encountered by the surgical team were caused by bullet
      deformation. Before hitting the body, the projectile pierced a mobile phone that
      was in the pocket of the woman's jacket, subsequently causing a large atypical
      secondary entrance wound. The experiment confirmed that, when the projectile
      passed through an obstacle with consequent deformation, it caused more extensive
      gunshot wounds, both at the entrance and at the exit, as well as more severe
      damage to the bones.

PMID- 28498137
TI  - Physical and Organizational Job Stressors in Pregnancy and Associations With
      Primary Cesarean Deliveries.
AB  - OBJECTIVE: The aim of this study was to assess the relationship between exposure
      to physical and organizational job stressors during pregnancy and cesarean
      delivery. METHODS: We sampled 580 employed women in California who participated
      in a nested population-based case-control study of birth outcomes. Adjusted
      multivariate regression analyses estimated associations between heavy lifting,
      frequent bending, high noise, extreme temperature, prolonged standing and
      organizational stressors (shift work, inflexible schedules, effort-reward ratio),
      and primary cesarean (vs vaginal) delivery, controlling for covariates. RESULTS:
      Women occupationally exposed had higher odds of cesarean. Those exposed to daily
      manual lifting more than 15 pounds [adjusted odds ratio = 2.54; 95% confidence
      interval (95% CI) 1.21 to 5.32] and at least four physical job stressors
      (adjusted odds ratio = 3.49; 95% CI 1.21 to 10.09) had significantly elevated
      odds of cesarean delivery. Exposed morbid women experienced greater risk; risk
      was lower among those with schedule flexibility. CONCLUSION: Associations were
      found between modifiable exposure to physical job stressors during pregnancy and
      cesarean delivery.

PMID- 28498138
TI  - Epidural Injection of Platelet Rich Plasma for Postlumbar Puncture Headaches.

PMID- 28498139
TI  - JNA Journal Club.

PMID- 28498140
TI  - Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In
      Vitro Assessed by Thromboelastometry.
AB  - BACKGROUND: Albumin and mannitol may interfere with hemostasis, but their
      coinfluence is unclear. We aimed to determine the effects of albumin alone and in
      combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in
      vitro study. MATERIALS AND METHODS: From citrated fresh whole blood withdrawn
      from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4%
      albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man
      group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM
      (fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed. RESULTS: A
      20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot
      formation time, alpha-angle decrease, and maximum clot firmness (MCF) weakening
      compared with undiluted sample (P<0.05). Clot formation time prolonged more in
      Alb5/Man than in Alb5 and Alb5/RAC dilution (P<0.05). In Alb2.5/Man, Alb10/Man,
      and Alb15/Man, dilution alpha-angle was lower than in corresponding Alb/RAC and
      Alb-group dilutions (P<0.05). In ExTEM, MCF decreased similarly in every dilution
      of Alb/Man and Alb/RAC compared with Alb group (P<0.05). In FibTEM, MCF decreased
      more in Alb10/Man than in Alb10/RAC dilution (P<0.05). CONCLUSIONS: In up to 15
      vol% dilutions, albumin alone did not impair hemostasis in vitro, but in
      combination with mannitol or RAC coagulation was disturbed similarly at most
      concentrations. There was some significant additional effect with mannitol at
      certain concentrations. Our results indicate that coadministration of mannitol
      and albumin needs further study in vivo.

PMID- 28498141
TI  - The ASA Committee for Neuroanesthesia and Anesthesia Quality Institute: Report
      for Demographic Patterns for Neurosurgical Anesthesia Practice in the United
      States.

PMID- 28498142
TI  - Inflammatory Myopathy and Axonal Neuropathy in a Patient With Melanoma Following
      Pembrolizumab Treatment.
AB  - Immune-mediated adverse effects of immune checkpoint inhibitors are rather
      common, but neuromyopathic immune-related adverse events are very rare. In this
      report, we present a unique case of a patient with a complex neuromyopathic
      syndrome with axonal neuropathy and inflammatory myopathy after a single dose of
      pembrolizumab. An 82-year-old patient with a previously untreated stage IIIc
      melanoma developed ptosis in the left eye, generalized weakness, and neck and
      shoulder pain 15 days after pembrolizumab administration. He had left-sided
      ptosis and miosis, with a normal pupillary light reflex, horizontal diplopia, and
      voice hoarseness, along with weakness of the neck muscles and a hypokinetic right
      vocal cord at laryngoscopy. The laboratory evaluation was remarkable for the
      marked increase in the serum lactate dehydrogenase and creatine phosphokinase
      levels. Further evaluation revealed findings compatible with axonal neuropathy
      and inflammatory myopathy. The patient was treated with corticosteroids,
      immunoglobulin, and plasmapheresis, with a minor response; the patient eventually
      died. This case represents a newly described syndrome probably associated with
      pembrolizumab administration.

PMID- 28498143
TI  - The Crucible simulation: Behavioral simulation improves clinical leadership
      skills and understanding of complex health policy change.
AB  - BACKGROUND: The Health and Social Care Act 2012 represents the most complex
      National Health Service reforms in history. High-quality clinical leadership is
      important for successful implementation of health service reform. However, little
      is known about the effectiveness of current leadership training. PURPOSE: This
      study describes the use of a behavioral simulation to improve the knowledge and
      leadership of a cohort of medical doctors expected to take leadership roles in
      the National Health Service. METHODOLOGY: A day-long behavioral simulation (The
      Crucible) was developed and run based on a fictitious but realistic health
      economy. Participants completed pre- and postsimulation questionnaires generating
      qualitative and quantitative data. Leadership skills, knowledge, and behavior
      change processes described by the "theory of planned behavior" were self-assessed
      pre- and postsimulation. RESULTS: Sixty-nine medical doctors attended.
      Participants deemed the simulation immersive and relevant. Significant
      improvements were shown in perceived knowledge, capability, attitudes, subjective
      norms, intentions, and leadership competency following the program. Nearly one
      third of participants reported that they had implemented knowledge and skills
      from the simulation into practice within 4 weeks. CONCLUSIONS: This study
      systematically demonstrates the effectiveness of behavioral simulation for
      clinical management training and understanding of health policy reform. Potential
      future uses and strategies for analysis are discussed. PRACTICE IMPLICATIONS:
      High-quality care requires understanding of health systems and strong leadership.
      Policymakers should consider the use of behavioral simulation to improve
      understanding of health service reform and development of leadership skills in
      clinicians, who readily adopt skills from simulation into everyday practice.

PMID- 28498144
TI  - The Impact of Preexposure Prophylaxis Among Men Who Have Sex With Men: An
      Individual-Based Model.
AB  - OBJECTIVES: Preexposure prophylaxis (PrEP) is recommended for preventing HIV
      infection among individuals at high risk, including men who have sex with men
      (MSM). Although its individual-level efficacy is proven, questions remain
      regarding population-level impact of PrEP implementation. DESIGN: We developed an
      agent-based simulation of HIV transmission among MSM, accounting for
      demographics, sexual contact network, HIV disease stage, and use of
      antiretroviral therapy. We use this framework to compare PrEP delivery strategies
      in terms of impact on HIV incidence and prevalence. RESULTS: The projected
      reduction in HIV incidence achievable with PrEP reflects both population-level
      coverage and individual-level adherence (as a proportion of days protected
      against HIV transmission). For example, provision of PrEP to 40% of HIV-negative
      MSM reporting more than one sexual partner in the last 12 months, taken with
      sufficient adherence to provide protection on 40% of days, can reduce HIV
      incidence by 9.5% (95% uncertainty range: 8%-11%) within 5 years. However, if
      this could be increased to 80% coverage on 80% of days (eg, through mass
      campaigns with a long-acting injectable formulation), a 43% (42%-44%) reduction
      in HIV incidence could be achieved. Delivering PrEP to MSM at high risk for HIV
      acquisition can augment population-level impact up to 1.8-fold. CONCLUSIONS: If
      highly ambitious targets for coverage and adherence can be achieved, PrEP can
      substantially reduce HIV incidence in the short-term. Although the reduction in
      HIV incidence largely reflects the proportion of person-years protected, the
      efficiency of PrEP delivery can be enhanced by targeting high-risk populations.

PMID- 28498145
TI  - Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals
      Prospective Data From an Asian Cohort.
AB  - BACKGROUND: The magnitude and risk factors of progression of atherosclerosis in
      Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1)
      the rate of progression of atherosclerosis in HIV-infected individuals, and (2)
      metabolic and inflammatory parameters that may predict atherosclerosis
      progression in HIV-infected individuals in an Asian cohort. SETTING: A
      prospective, longitudinal study was performed among adults attending an HIV
      Metabolic clinic in Hong Kong. METHODS: Carotid intima media thickness (cIMT) was
      measured at baseline and 24 months. Body composition, metabolic, and inflammatory
      biomarkers [including homeostasis model assessment of insulin resistance, LDL
      (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive
      protein, adiponectin] associated with cIMT change were analyzed; their predictive
      performances were estimated using receiver operating characteristic analyses.
      RESULTS: Sixty-one HIV-infected individuals (mean +/- SD age 49.8 +/- 11.4 years,
      89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were
      recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and
      19% developed new plaque at 24 months. Two patients died during the study period,
      1 because of sudden cardiac death. Using receiver operating characteristic
      analyses, combination of lower limb fat percentage, LDL cholesterol subclass
      pattern B, and lower adiponectin level, but not Framingham score, predicted
      greater cIMT progression in HIV-infected individuals. CONCLUSIONS: Asian HIV
      infected individuals had atherosclerosis progression. Limb fat percentage, LDL
      cholesterol particle size, and adiponectin level may identify at-risk Asian HIV
      infected individuals for early intervention.

PMID- 28498146
TI  - First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected
      Children Treated Through the Universal Coverage Health Program in Thailand.
AB  - BACKGROUND: We assessed the treatment outcomes on first-line antiretroviral
      therapy (ART), and factors associated with switching regimen in HIV-infected
      children treated through the universal coverage health program (UC) in Thailand.
      METHODS: Children aged <15 years at ART initiation who had been receiving ART for
      at least 6 months between 2008 and 2014 through UC were included in the analysis.
      The Kaplan-Meier method was used to estimate immunological recovery (IMR),
      immunological failure, and virological failure (VF). Cox models were used to
      assess predictors of IMR and VF. Competing risk models were used to assess
      factors associated with switching to a second-line regimen, with death considered
      as a competing risk. RESULTS: A total of 4120 children initiated ART at a median
      (interquartile range) age of 9.3 (5.8-12.0) years. The median duration of ART was
      3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five
      children achieved IMR, and the probability of IMR increased to 76% by 3 years
      after ART initiation. Among 1054 children switched to second-line regimens, 84%
      had VF and 19% had immunological failure. The cumulative rate of switching
      regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged
      >=12 years at ART initiation, starting with nonnucleoside reverse-transcriptase
      inhibitors, and baseline CD4% <10% had an increased risk of switching to second
      line regimens. CONCLUSIONS: Children receiving ART through UC had good treatment
      outcomes, although a fifth required switching regimen by 3 years. Earlier
      treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor
      first-line regimens in high-risk children may prevent treatment failure.

PMID- 28498147
TI  - Reply.

PMID- 28498148
TI  - Striatal activity is modulated by target probability.
AB  - Target probability has well-known neural effects. In the brain, target
      probability is known to affect frontal activity, with lower probability targets
      producing more prefrontal activation than those that occur with higher
      probability. Although the effect of target probability on cortical activity is
      well specified, its effect on subcortical structures such as the striatum is less
      well understood. Here, I examined this issue and found that the striatum was
      highly responsive to target probability. This is consistent with its hypothesized
      role in the gating of salient information into higher-order task representations.
      The current data are interpreted in light of that fact that different components
      of the striatum are sensitive to different types of task-relevant information.

PMID- 28498149
TI  - Inhibition of glutamate release by cilnidipine in rat cerebrocortical nerve
      terminals (synaptosomes).
AB  - Cilnidipine is an antihypertensive drug that was reported to have a
      neuroprotective profile. The present study aimed to investigate the effect of
      cilnidipine on the 4-aminopyridine (4-AP)-induced glutamate release in the rat
      cerebral cortex using isolated nerve terminals (synaptosomes). Cilnidipine
      reduced the release of glutamate release induced by 4-AP in a concentration
      dependent manner. This inhibitory effect was associated with a reduction in the 4
      AP-induced intrasynaptosomal Ca concentration elevation and was not because of an
      alteration of the synaptosomal membrane potential. The inhibition of glutamate
      release by cilnidipine was markedly reduced or eliminated in the presence of the
      Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker omega-conotoxin MVIIC and
      the protein kinase A inhibitor H89. The intracellular Ca-release inhibitors
      dantrolene and CGP37157, the mitogen-activated protein kinase inhibitor PD98059
      or the protein kinase C inhibitor GF109203X failed to affect the action of
      cilnidipine. These results suggest that cilnidipine inhibits glutamate release
      from rat cortical synaptosomes through the suppression of presynaptic voltage
      dependent Ca entry and protein kinase A activity.

PMID- 28498150
TI  - Effect of insulin on spatial memory in aluminum chloride-induced dementia in
      rats.
AB  - Latest reports suggest the involvement of insulin in modulating memory. A few
      published in-vitro studies favor the antidementia effect of insulin. Thus, the
      present study aimed to evaluate the prophylactic role of insulin and its
      combination with glucose and its possible mechanism(s) in an aluminum chloride
      (AlCl3)-induced cognitive dysfunction model in rodents, with a special focus on
      memory centers namely, the hippocampus and the frontal cortex. Male Wistar rats
      were exposed to AlCl3 (175 mg/kg orally) for 60 days. Insulin (0.5 IU/kg),
      Insulin (0.5 IU/kg) in combination with glucose (200 mg/kg), and rivastigmine (1
      mg/kg) were administered intraperitoneally 45 min before the administration of
      AlCl3 for 60 days. Spatial memory was assessed using the Morris water-maze test.
      After 60 days of treatment, animals were killed, and the hippocampus and frontal
      cortex were collected and analyzed for acetylcholinesterase activity and
      antioxidant enzyme level. Blood glucose levels were also analyzed. Treatment with
      the standard drug, rivastigmine (1 mg/kg), produced a significant reduction in
      escape latency and increased the time spent in the target quadrant compared with
      the AlCl3-treated group. Insulin and its combination with glucose could not
      inhibit the behavioral impairments in aluminum-exposed rats. Treatment with
      insulin alone and its combination with glucose reversed the increased glucose
      levels. Insulin alone and its combination with glucose could not inhibit aluminum
      induced oxidative stress and impaired cholinergic transmission in the hippocampus
      and frontal cortex regions. The study suggests the inability of prophylactic
      insulin administration against cognitive dysfunction induced by environmental
      toxin (AlCl3) in the hippocampus and the frontal cortex.

PMID- 28498152
TI  - Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with
      Microscopic Colitis and Ulcerative Colitis.
AB  - BACKGROUND: Microscopic colitis (MC), comprising collagenous colitis (CC) and
      lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases.
      Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.
      METHODS: To understand diversity and clonality of infiltrating T cells, we
      analyzed the T-cell receptor beta (TCRbeta) chains in colonic biopsies of MC,
      ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological
      remission] or UC-R [remission]) compared with patients with noninflamed colons
      using next-generation sequencing. RESULTS: Compared with controls and patients
      with CC, patients with LC had significantly lower diversity with significantly
      lower evenness and richness in TCRVbeta-Jbeta gene segments. Similarly, patients
      with LC-HR had lower diversity because of significantly lower TCRVbeta-Jbeta
      clone richness. Patients with UC and UC-R showed significantly higher diversity
      and richness. Univariate and multivariate analyses were performed to identify
      TCRVbeta-Jbeta gene segments differentiating disease types from controls or their
      remission counterparts. Patients with LC were discriminated from controls by 12
      clones and from patients with CC by 8 clones. Neither univariate nor multivariate
      analyses showed significance for patients with CC or CC-HR compared with
      controls. Patients with UC and UC-R had 16 and 14 discriminating clones,
      respectively, compared with controls. CONCLUSIONS: Altogether, patients with MC
      and UC showed an oligoclonal TCRbeta distribution. TCRVbeta-Jbeta clone types and
      their diversity were distinctive between patients with CC and LC, as well as for
      patients with UC, suggesting different pathophysiological mechanisms according to
      disease type and stage. This study suggests that CC and LC are different entities
      because of differences in immunoregulatory responses, as mirrored by their T-cell
      repertoire.

PMID- 28498153
TI  - Infliximab Trough Levels at Induction to Predict Treatment Failure During
      Maintenance.
AB  - BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel
      diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to
      10% to 30% of patients within the first year of treatment. Our objective was to
      evaluate the impact of the pharmacokinetics of IFX at induction on treatment
      failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD
      treated with IFX in a single center. A total of 2331 blood samples were
      prospectively collected from 2007 until March 2015 with a retrospective analysis
      of clinical data. IFX trough levels (TLs) were measured by enzyme-linked
      immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging
      assay. RESULTS: During follow-up, patients were defined according to treatment
      outcome. At week 6, median IFX TL in patients requiring a switch to another
      treatment due to LOR (LOR switched group) (2.32 MUg/mL [0.12-19.93 MUg/mL]) was
      lower than in patients with long-term response (long-term responders) (8.66
      MUg/mL [0.12-12.09 MUg/mL], P = 0.007) and in patients responding to optimization
      (LOR optimized group) (7.28 MUg/mL [0.17-14.91 MUg/mL], P = 0.021). At week 2,
      median IFX TL was lower in the LOR switched group (5.7 MUg/mL [0.15-12.09
      MUg/mL]) compared with the long-term responders (11.92 MUg/mL [0.14-19.93
      MUg/mL], P = 0.041) but no significant difference was reached with the LOR
      optimized group (11.91 MUg/mL [0.23-12.09 MUg/mL], P = 0.065). In the LOR
      switched group, median IFX TL at induction (weeks 2 and 6) was significantly
      lower when patients had been previously exposed to anti-tumor necrosis factor
      compared with naive patients (0.91 MUg/mL [0.12-4.4 MUg/mL] versus 6.6 MUg/mL
      [0.15-19.93 MUg/mL], P = 0.044). CONCLUSIONS: This study suggests that patients
      who do not respond to any optimization strategy have lower IFX TLs during
      induction at week 6. IFX TLs measured early on at induction might predict
      treatment failure to IFX during maintenance.

PMID- 28498154
TI  - Pediatric-to-adult Transition and Medication Adherence in Patients with
      Inflammatory Bowel Disease.
AB  - BACKGROUND: Medication nonadherence is common in inflammatory bowel disease and
      is associated with poor outcomes. There has been no study on pediatric-to-adult
      transition as a risk factor for nonadherence in inflammatory bowel disease, which
      has been demonstrated in other diseases. We aimed to assess whether transitioned
      (TR) patients have higher nonadherence rates than young adults (YAs) diagnosed in
      adulthood. METHODS: Consecutive ambulatory subjects were prospectively recruited
      and completed the validated Medication Adherence Reporting Scale (MARS), with the
      primary outcome being adherence differences between group age-matched TR and YA
      groups. Pediatric subjects were taken as the control group. Perceptions of
      medication-related necessity and concerns were assessed with the Beliefs about
      Medicines Questionnaire (BMQ). Nonadherers (defined as MARS <=16) received the
      Inflammatory Bowel Diseases Pharmacist Adherence Counselling (IPAC) intervention
      and adherence change was reassessed after 6 months as a secondary outcome.
      RESULTS: Adherence in TR patients (n = 38, mean age 20.4, 13.2% nonadherent) was
      noninferior to and numerically better than YAs diagnosed in adulthood (n = 41,
      mean age 21.2, 24.4%). Nonadherence in the pediatric control group (n = 50, mean
      age 14.7) was 8.0%. YAs had significantly higher medication-related concerns
      (14.6 versus 11.9, P = 0.02) than the pediatric group. The IPAC intervention
      reduced nonadherence rates by 60% (P = 0.004). CONCLUSIONS: TR patients did not
      have worse adherence than YAs diagnosed in adulthood. Protective factors may
      include previous treatment in pediatric centers and the salient symptomatology of
      inflammatory bowel disease, whereas increasing concerns over medications
      contribute to nonadherence in YAs. Pharmacist-led counselling improves adherence
      in these patients.

PMID- 28498155
TI  - Therapeutic Drug Monitoring to Guide Infliximab Dose Adjustment is Associated
      with Better Endoscopic Outcomes than Clinical Decision Making Alone in Active
      Inflammatory Bowel Disease.
AB  - BACKGROUND: Adequate infliximab (IFX) levels are associated with favorable
      outcomes in inflammatory bowel disease. Using therapeutic drug monitoring (TDM)
      to guide dosing is cost effective and associated with clinical improvement, but
      effect on endoscopic outcomes remains unclear. METHODS: Primary responders to IFX
      who underwent dose escalation (2008-2014) were reviewed. Patients with active
      endoscopic disease were included. Two cohorts were examined: TDM-based decision
      to escalate (TDM) and clinical decision (non-TDM). Outcomes recorded at median 6
      months after adjustment included endoscopic remission (Mayo <1, Simple Endoscopic
      Score for Crohn's Disease <3), C-reactive protein, and inflammatory bowel disease
      specific health care utilization. Postadjustment IFX and antibodies to infliximab
      levels discriminant for endoscopic remission were determined. Multivariable
      regression evaluated independent predictors of remission. RESULTS: Of note, 312
      dose optimizations were examined (149 TDM and 163 non-TDM). Clinically, groups
      were similar. Sixty-three percent TDM attained postadjustment endoscopic
      remission compared with 48% non-TDM (P < 0.05). Sixty-nine percentage TDM had
      significant clinical response (57% non-TDM [P < 0.01]); fewer were hospitalized
      (22% TDM versus 35% non-TDM, P = 0.025). Patients with ulcerative colitis had
      shorter time to escalation (10 versus 20 mo, P < 0.0001). Median IFX levels
      increased after escalation in TDM (1.5 [pre] and 11 MUg/mL [post]; P < 0.0001)
      and were higher than non-TDM postadjustment levels (11 versus 6.5 MUg/mL, P =
      0.015). Postadjustment IFX >4.5 MUg/mL (area under curve = 0.8; 95% confidence
      interval, 0.71-0.88) and antibodies to infliximab <3.3 U/mL (area under curve =
      0.70; 95% confidence interval, 0.63-0.81) were associated with endoscopic
      remission. Multivariable analysis showed that IFX concentration (odds ratio 1.2
      [95% confidence interval, 1.1-1.3]; P < 0.0001) remained an independent predictor
      of endoscopic remission. CONCLUSIONS: TDM before dose adjustment is associated
      with higher postadjustment levels and endoscopic remission.

PMID- 28498156
TI  - Coping with Inflammatory Bowel Disease: Engaging with Information to Inform
      Health-Related Decision Making in Daily Life.
AB  - BACKGROUND: People with inflammatory bowel disease (IBD) require disease and
      lifestyle information to make health-related decisions in their daily lives.
      Derived from a larger qualitative study of the lived experiences of people with
      IBD, we report on findings that explored how people with IBD engage with health
      related information in their daily lives. METHODS: Participants were recruited
      primarily from the Manitoba IBD Cohort Study. We used purposive sampling to
      select people with a breadth of characteristics and experiences. Individual
      interviews were audio-recorded and transcribed verbatim. Data were analyzed using
      inductive qualitative methods consistent with a phenomenological approach.
      RESULTS: Forty-five people with IBD participated; 51% were women. Findings
      highlighted the temporal and contextual influences on engagement with health
      related information. Temporal influences were described as the changing need for
      health-related information over time. Participants identified 6 contextual
      factors influencing engagement with information to make health decisions: (1)
      emotional and attitudinal responses, (2) perceived benefits and risks, (3) trust
      in the source of the information, (4) knowledge and skills to access and use
      information, (5) availability of evidence to support decisions, and (6) social
      and economic environments. CONCLUSIONS: Findings illustrate the changing needs
      for health-related information over the course of IBD, and with evolving health
      and life circumstances. Practitioners can be responsive to information needs of
      people with IBD by having high-quality information available at the right time in
      a variety of formats and by supporting the incorporation of information in daily
      life.

PMID- 28498157
TI  - Compositional Changes in the Gut Mucus Microbiota Precede the Onset of Colitis
      Induced Inflammation.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is associated with an inappropriate
      immune response to the gut microbiota. Notably, patients with IBD reportedly have
      alterations in fecal microbiota. However, the colonic microbiota occupies both
      the gut lumen and the mucus covering the epithelium. Thus, information about
      mucus-resident microbiota fails to be conveyed in the routine microbiota analyses
      of stool samples. Further, studies analyzing microbiota in IBD have mainly
      focused on stool samples taken after onset of inflammation. Our objective was to
      investigate both temporal and spatial changes in colonic microbiota communities
      preceding the onset of colitis. METHODS: We studied mucus and stool microbiota
      using a spontaneous model of colitis, the mdr1a mouse, and their respective wild
      type littermate controls in a time series mode. RESULTS: Using this approach we
      have shown that microbial dysbiosis was evident in the mucus but not stools, with
      reduced abundance of Clostridiales evident in the mucus but not stools, of
      colitis-prone mice mdr1a mice 12 weeks before the onset of detectable
      inflammation. This altered microbial composition was coupled with a significantly
      thinner mucus layer. On emergence of inflammation, dysbiosis was evident in the
      stools and at this time point, the spatial segregation between microbiota and
      host tissue was also disrupted, correlating with worsened inflammation. Our
      results reveal that microbial dysbiosis is detectable before changes in the
      stools. Importantly, dysbiosis in the mucus layer preceded development of
      colitis. CONCLUSIONS: Our data reveal the importance of mucus sampling for
      understanding the underlying etiology of IBD and fundamental processes underlying
      disease progression.

PMID- 28498158
TI  - Transmural Healing Is Associated with Improved Long-term Outcomes of Patients
      with Crohn's Disease.
AB  - BACKGROUND: Mucosal healing (MH) is currently accepted as one of the best
      treatment targets in Crohn's disease. However, even in patients with sustained
      MH, residual bowel wall inflammation can still be detected by cross-sectional
      imaging. The long-term benefits of obtaining transmural healing (TH) have not
      been previously assessed. METHODS: We performed an observational study including
      214 patients with Crohn's disease with a magnetic resonance enterography (MRE)
      and colonoscopy performed within a 6-month interval. Patients were classified as
      having TH (inactive MRE and colonoscopy), MH (active MRE with inactive
      colonoscopy), or no healing (active colonoscopy). Need for surgery, hospital
      admission, and therapy escalation were evaluated at 12 months of follow-up.
      RESULTS: Patients with TH presented lower rates of hospital admission, therapy
      escalation, and surgery than patients with MH or no healing. In logistic
      regression analysis, endoscopic remission (odds ratio 0.331 95% confidence
      interval [0.178-0.614], P < 0.001) and MRE remission (odds ratio 0.270 95%
      confidence interval [0.130-0.564], P < 0.001) were independently associated with
      a lower likelihood of reaching any unfavorable outcome. CONCLUSIONS: TH is
      associated with improved long-term outcomes in Crohn's disease and may be a more
      suitable target than MH.

PMID- 28498160
TI  - Not all measurement instruments are created equal.

PMID- 28498159
TI  - Fecal Calprotectin Is Not Affected by Pregnancy: Clinical Implications for the
      Management of Pregnant Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Noninvasive biomarkers of inflammation for monitoring inflammatory
      bowel disease (IBD) are important in pregnancy. Clinical and laboratory markers
      are often affected by the physiological adaption that occurs during pregnancy,
      although, few, if any, data exist on fecal calprotectin (FC). We investigated FC
      concentrations in pregnant controls and IBD women, and whether FC correlated with
      physician global assessment (PGA), C-reactive protein (CRP), and Harvey-Bradshaw
      Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) before and after
      pregnancy, as well as during each trimester. METHODS: The study is a prospective
      multicenter study of 46 pregnant women with and 21 without IBD in Denmark,
      Australia, and New Zealand. Demographics, clinical parameters, and HBI/SCCAI were
      recorded. Stool and blood samples were obtained to determine FC and CRP
      concentrations. RESULTS: From pregnant IBD women and pregnant controls, 174 and
      21 fecal samples were collected, respectively. The median FC concentration in
      pregnant IBD women was 131 MUg/g (range 0-3600) and in controls 0 MUg/g (range 0
      84) (P < 0.0001). FC strongly correlated with PGA at all 5 timepoints (r >= 0.80;
      P < 0.0001) and with HBI/SCCAI before (r = 0.66; P < 0.0001) and after pregnancy
      (r = 0.47; P < 0.003) but not during pregnancy (P > 0.05). An FC cutoff
      concentration of 250 MUg/g significantly correlated with active disease according
      to PGA in all 5 periods (P <= 0.0002). CRP only significantly correlated with FC
      (P = 0.0007) and PGA in the second trimester (P = 0.0003). No significant
      correlation was found between CRP and HBI/SCCAI at any timepoint (P > 0.05).
      CONCLUSIONS: The physiological changes that occur during pregnancy do not affect
      FC, in contrast to CRP and HBI/SCCAI. The combined use of FC and PGA seems
      optimal to assess disease activity in IBD during pregnancy.

PMID- 28498161
TI  - Pediatric tonsillectomy quality of life assessment instruments: a scoping review
      protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to investigate
      quality of life (QoL) questionnaires available to pediatric patients following
      tonsillectomies with or without adenoidectomies for chronic infection or sleep
      disordered breathing (SDB). The scoping review will aim to map the components of
      each QoL questionnaire assessed including frequency of use, age parameters,
      respondent, domains assessed, format and psychometric properties. Questionnaire
      format will be summarized into respondent and administrator burden by identifying
      the number of questions present, scale utilized and time to completion. The
      scoping review will report on whether psychometric analysis in terms of test
      reliability and validity was assessed in the included papers as well as the
      results of those assessments.Specifically, the review question is: what QoL
      questionnaires are available for pediatric patients following tonsillectomies
      with or without adenoidectomies for chronic infections or SDB?

PMID- 28498162
TI  - Effectiveness of psychosocial interventions on the psychological health and
      wellbeing of family carers of people with dementia following residential care
      placement: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify, appraise
      and synthesize existing evidence regarding the effectiveness of psychosocial
      interventions on the psychological health and emotional wellbeing of family
      carers of people with dementia who have moved into residential care.More
      specifically, the objectives are to determine the effectiveness of psychosocial
      interventions on any of these family carer outcomes after placement in
      residential care: burden, anxiety, stress, depression, guilt, grief and loss,
      quality of life and satisfaction with the care of the person with dementia.

PMID- 28498163
TI  - Oral hygiene in patients with chronic obstructive pulmonary disease: a scoping
      review protocol.
AB  - SCOPING REVIEW OBJECTIVE: It is hypothesized that systematic oral hygiene may
      reduce airway infections in patients with chronic obstructive pulmonary disease
      (COPD). Before considering doing a systematic review, a scoping review is
      necessary to explore and map literature on the subject and identify which
      interventions have been carried out, if there is relevant literature available
      for a systematic review, or if further research should be initiated.The objective
      of this scoping review is to comprehensively identify and describe qualitative or
      quantitative literature reporting of non-invasive interventions that have been
      carried out to improve oral hygiene and relieve and/or reduce respiratory tract
      infections, exacerbation and/or hospital readmission in patients with diagnosed
      with COPD. A further objective is to undertake a comprehensive search to identify
      qualitative literature reporting on the experiences of oral hygiene in people
      diagnosed with COPD and/or their relatives and/or healthcare providers
      (HCPs).Specifically, the scoping review questions are as follows.

PMID- 28498164
TI  - Functional status and physical impairments of adult patients infected with the
      human immunodeficiency virus admitted to hospital: a scoping review protocol.
AB  - RESEARCH QUESTION/OBJECTIVE: The objectives of this scoping review are to
      describe the physical impairments and subsequent level of function of adult
      individuals infected with the human immunodeficiency virus (HIV) admitted to an
      acute care hospital, determine the outcome measures used by rehabilitation
      professionals when evaluating said impairments and level of function in the
      population of interest, and identify the rehabilitation interventions offered to
      individuals while in hospital as a means of addressing these physical impairments
      and individuals' functional status.Specifically, the research questions are:The
      current scoping review will comprehensively identify the physical impairments of
      people living with HIV when admitted to an acute care hospital and highlight the
      subsequent influence on their level of function as a means of emphasizing the
      disability present. Findings regarding the rehabilitation interventions offered
      could inform clinical practice as a means of mapping which interventions are
      offered to address the related physical impairments and thus highlight areas for
      future research.

PMID- 28498165
TI  - Experiences of the home-dwelling elderly in the use of telecare in home care
      services: a qualitative systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify
      and synthesize the best evidence on the home-dwelling elderly's experiences with
      the use of telecare in home care services. Furthermore, the study will identify
      experiences with telecare devices and examine what beliefs the home-dwelling
      elderly hold regarding the impact of telecare on the ability to age in
      place.Review question 1: How do the home-dwelling elderly experience the use of
      telecare in the context of home care services?Review question 2: How do the home
      dwelling elderly experience telecare devices?Review question 3: What beliefs do
      the home-dwelling elderly hold regarding the impact of telecare on the ability to
      age in place?

PMID- 28498166
TI  - Effectiveness of telehealth on correctional facility health care: a systematic
      review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify the
      effectiveness of telehealth in improving correctional facility health care. The
      outcomes of the review will include the primary outcomes of access to health care
      and costs associated with health care and the secondary outcome of virologic
      suppression.Specifically, the review question is: What is the effect of
      telehealth compared to usual care on improving correctional facility health care
      and decreasing costs in correctional facility health care?

PMID- 28498167
TI  - New midwives' experiences of transition support during their first year of
      practice: a qualitative systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The current review aims to investigate new midwives'
      experiences of transition support during their first year of practice as
      registered midwives. A further objective is to identify the social support
      experiences of new midwives during their first year of practice as registered
      midwives.Specifically, the review question is: How do new graduate midwives
      experience transition and social support during their first year of practice?

PMID- 28498168
TI  - Effectiveness of formal hand hygiene education and feedback on healthcare
      workers' hand hygiene compliance and hospital-associated infections in adult
      intensive care units: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this quantitative systematic review
      is to identify and synthesize evidence on the effectiveness of formal hand
      hygiene education with and without feedback on healthcare workers' hand hygiene
      compliance and healthcare-associated infections in adult intensive care units.

PMID- 28498169
TI  - Experiences and expectations of return-to-work programs for nurses and midwives
      who have acquired a musculoskeletal disorder in the workplace: a qualitative
      systemic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify
      and synthesize the best available evidence on the experiences and expectations of
      being involved in a program that aims to return nurses and midwives, who have
      acquired a musculoskeletal disorder (MSD) in the workplace, to work.The specific
      review questions are.

PMID- 28498170
TI  - Coping with Parkinson's disease in everyday life: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The purpose of this systematic review is to synthesize
      the best available qualitative evidence on how individuals with Parkinson's
      disease cope with the disease in daily life.

PMID- 28498171
TI  - Experiences of unpaid family/friend caregivers of community-dwelling adults with
      dementia: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of the review is to synthesize evidence
      regarding the experiences of unpaid caregivers of community-dwelling adults with
      dementia. Specifically, the review question is: What are the experiences and
      perceptions of unpaid caregivers providing care for community-dwelling adults
      with dementia?

PMID- 28498172
TI  - Effectiveness of Patient Safety Leadership WalkRoundsTM on patient safety
      culture: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The review objective is to synthesize the effect of
      Patient Safety Leadership WalkRounds (PSLWs) on patient safety culture
      (PSC).Specifically, the review question is: What is the effect of PSLWs on the
      PSC in hospitals, measured with validated surveys?

PMID- 28498173
TI  - The meaning of confidence for older people living with frailty: a qualitative
      systematic review.
AB  - BACKGROUND: In many countries, the oldest old (those aged 85 years and older) are
      now the fastest growing proportion of the total population. This oldest
      population will increasingly be living with the clinical condition of frailty.
      Frailty syndromes negatively impact on the person as they do the healthcare
      systems supporting them. Within healthcare literature "loss of confidence" is
      occasionally connected to older people living with frailty, but ambiguously
      described. Understanding the concept of confidence within the context of frailty
      could inform interventions to meet this growing challenge. OBJECTIVES: The
      objective of this systematic review was to explore the meaning of confidence from
      the perspective of older people living with frailty through synthesis of
      qualitative evidence to inform healthcare practice, research and policy.
      INCLUSION CRITERIA TYPES OF PARTICIPANTS: Studies that included frail adults,
      aged over 60 years, experiencing acute hospital and or post-acute care in the
      last 12 months. PHENOMENA OF INTEREST: The concept of "confidence" and its impact
      on the physical health and mental well-being of older people living with frailty.
      CONTEXT: Studies that reported on the older person's descriptions, understanding
      and meaning of confidence in relation to their frailty or recent healthcare
      experiences. TYPES OF STUDIES: Studies of qualitative design and method. SEARCH
      STRATEGY: A three step search strategy was used. The search strategy explored
      published studies and gray literature. Publications in English from the last 20
      years were considered for inclusion. METHODOLOGICAL QUALITY: All included
      articles were assessed by two independent reviewers using the Joanna Briggs
      Institute Qualitative Assessment Review Instrument (JBI-QARI). DATA EXTRACTION:
      Data were extracted from included studies using the data extraction tools
      developed by the Joanna Briggs Institute. DATA SYNTHESIS: Qualitative research
      findings were collated using a meta-aggregative approach and JBI-QARI software.
      RESULTS: Synthesized findings of this review were drawn from just four research
      studies that met the inclusion criteria. Only six findings contributed to the
      creation of three categories. These informed a single synthesized finding:
      Vulnerability, described as a fragile state of well-being that is exposed to the
      conflicting tensions between physical, emotional and social factors. These
      tensions have the capability to enhance or erode this state. CONCLUSIONS:
      Assertions that an understanding of the concept confidence has been reached
      cannot be made. The review data offer limited insight into the concept of
      confidence being described by the cohort of older people living with frailty.

PMID- 28498174
TI  - Adult women's experiences of urinary incontinence: a systematic review of
      qualitative evidence.
AB  - BACKGROUND: Women are affected dramatically by urinary incontinence (UI). This
      disease is currently considered as epidemic. OBJECTIVE: The objective of this
      review is to identify, through the best available evidence, how women experience
      UI worldwide. INCLUSION CRITERIA TYPES OF PARTICIPANTS: The current review
      included studies of adult women who had experienced UI. PHENOMENA OF INTEREST:
      Women with UI from various social and cultural settings were included in this
      review. TYPES OF STUDIES: Qualitative data including, but not limited to, study
      designs such as phenomenology, grounded theory, ethnography, action research and
      feminist research were included in this review. OUTCOMES: All aspects related to
      the experience of UI endured by women were considered. SEARCH STRATEGY: An
      initial search of MEDLINE (PubMed) and CINAHL was done, followed by the
      exploration of all the databases and all identified studies, published in
      English, Spanish, French and Portuguese. The databases searched were CINAHL,
      PubMed, PsycINFO, Lilacs, Scielo, BVS, BVS-Psi, Scopus, Embase, Sociological
      Abstracts, Dissertation Abstracts International and the University of Sao Paulo
      Dissertations and Thesis bank and gray literature. METHODOLOGICAL QUALITY: Each
      primary study was assessed by two independent reviewers for methodological
      quality. The Joanna Briggs Institute Qualitative Appraisal and Review Instrument
      (JBI-QARI) data extraction form for interpretive and critical research was used
      to appraise the methodological quality of all papers. DATA EXTRACTION:
      Qualitative data were extracted using the JBI-QARI. DATA SYNTHESIS: Qualitative
      research findings were synthesized using the JBI-QARI. RESULTS: From the 28
      studies were included, 189 findings were extracted and they were grouped into 25
      categories and eight synthesized findings: (i) cultural and religious backgrounds
      and personal reluctance contribute to delays in seeking UI treatment; (ii) the
      inevitable and regrettable problem of UI endured silently and alone affects
      women's daily activities and their social roles; (iii) poor knowledge and the
      vague nature of the symptoms mask the fact that UI is a disease; (iv) the
      experiences provoked by UI and the sense of shame regarding the condition have
      contributed to impair women's lives; (v) UI has provoked negative effects on
      women's intimacy and sexual satisfaction and provoked changes in the ways they
      experience their sexuality and sexual function; (vi) UI is considered a
      consequence of pregnancy and childbirth, inherent to aging or a religious
      punishment; (vii) the women affected by UI adopt several strategies to improve
      their health status; and (viii) women have personal preferences toward care
      providers and treatments; they confront difficulties through UI treatment and
      some care needs are not met. CONCLUSION: Personal and tailored health care should
      be provided, and preferences and expectations should be taken into consideration
      in the provision of health care to the people affected by UI.

PMID- 28498175
TI  - Experiences of healthcare professionals of having their significant other
      admitted to an acute care facility: a qualitative systematic review.
AB  - BACKGROUND: Most healthcare professionals at some time will experience having a
      significant other admitted to an acute care hospital. The knowledge and
      understanding that these individuals possess because of their professional
      practice can potentially alter this experience. Expectations of staff and other
      family members (FMs) can potentially increase the burden on these health
      professionals. All FMs of patients should have their needs and expectations
      considered; however, this review specifically addresses what may be unique for
      healthcare professionals. OBJECTIVES: To synthesize the qualitative evidence on
      the experiences of healthcare professionals when their significant others are
      admitted to an acute care hospital. INCLUSION CRITERIA TYPES OF PARTICIPANTS: The
      current review considered studies reporting the experiences of healthcare
      professionals, specifically registered nurses (RNs) and physicians. PHENOMENA OF
      INTEREST: The experiences of RNs and physicians when a significant other is
      admitted to an acute care facility. TYPES OF STUDIES: Qualitative studies that
      have examined the phenomenon of interest including, but not limited to, designs
      such as phenomenology and grounded theory. SEARCH STRATEGY: The search strategy
      aimed to find both published and unpublished studies with no date restrictions.
      Only studies published in English were considered for inclusion in this review.
      METHODOLOGICAL QUALITY: Qualitative papers selected for retrieval were assessed
      using the standardized critical appraisal instrument from the Joanna Briggs
      Institute Qualitative Assessment and Review Instrument (JBI-QARI). DATA
      EXTRACTION: Data were extracted from the seven included papers using the
      standardized data extraction tool from JBI-QARI. DATA SYNTHESIS: The data were
      synthesized using the JBI approach to meta-synthesis by meta-aggregation using
      the JBI-QARI software and methods. RESULTS: Seven studies of moderate quality
      were included in the review. Forty findings were extracted and aggregated to
      create 10 categories, from which five synthesized findings were derived:
      CONCLUSION: In contrast to "lay" FMs, health professionals possess additional
      knowledge and understanding that alter their perceptions and expectations, and
      the expectations others have of them. This knowledge and understanding can be an
      advantage in navigating a complex health system but may also result in an
      additional burden such as role conflict.

PMID- 28498176
TI  - Effectiveness of haloperidol prophylaxis in critically ill patients with a high
      risk of delirium: a systematic review.
AB  - BACKGROUND: Delirium is associated with increased intensive care unit and
      hospital length of stay, prolonged duration of mechanical ventilation, unplanned
      removal of tubes and catheters, and increased morbidity and mortality.
      Prophylactic treatment with low-dose haloperidol may have beneficial effects for
      critically ill patients with a high risk of delirium. OBJECTIVES: To identify the
      effectiveness of haloperidol prophylaxis in critically ill patients with a high
      risk for delirium. INCLUSION CRITERIA TYPES OF PARTICIPANTS: Patients with a
      predicted high risk of delirium, aged 18 years or over, and in intensive care
      units. Patients with a history of concurrent antipsychotic medication use were
      excluded. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST: Haloperidol prophylaxis
      for preventing delirium. TYPES OF STUDIES: Experimental and epidemiological study
      designs. OUTCOMES: Primary outcome is the incidence of delirium. Secondary
      outcomes are duration of mechanical ventilation, incidence of re-intubation,
      incidence of unplanned/accidental removal of tubes/lines and catheters, intensive
      care unit and hospital length of stay, and re-admissions to both settings. SEARCH
      STRATEGY: An initial search of MEDLINE and CINAHL was undertaken, followed by a
      second search for published and unpublished studies from January 1967 to
      September 2015 in major healthcare-related electronic databases. Studies in
      English, Spanish and Portuguese were included. METHODOLOGICAL QUALITY: Two
      independent reviewers assessed the methodological quality of five studies using
      the standardized critical appraisal instrument from the Joanna Briggs Institute
      Meta-Analysis of Statistics Assessment and Review Instrument. There was general
      agreement among the reviewers to exclude one relevant study due to methodological
      quality. DATA EXTRACTION: Data were extracted using the JBI data extraction form
      for experimental studies and included details about the interventions,
      populations, study methods and outcomes of significance to the review questions.
      DATA SYNTHESIS: Significant differences were found between participants,
      interventions, outcome measures (clinical heterogeneity) and designs
      (methodological heterogeneity). For these reasons, we were unable to perform a
      meta-analysis. Therefore, the results have been described in a narrative format.
      RESULTS: Five studies met the inclusion criteria. One of these studies was
      excluded due to poor methodological quality. The remaining four original studies
      (total of 1142 patients) were included in this review. Three studies were
      randomized controlled trials and one was a cohort study.Two studies confirmed the
      effectiveness of haloperidol prophylaxis in critically ill patients with a high
      risk of delirium. These studies showed that short-term prophylactic
      administration of low-dose intravenous haloperidol significantly decreased the
      incidence of delirium in elderly patients admitted to intensive care units after
      non-cardiac surgery and in general intensive care unit patients with a high risk
      of delirium.However, the two remaining studies showed contradictory results in
      mechanically ventilated critically ill adults, revealing that the administration
      of haloperidol reduced delirium prevalence, delayed its occurrence, and/or
      shorten its duration. CONCLUSIONS: The evidence related to the effectiveness of
      haloperidol prophylaxis in critically ill patients with a high risk of delirium
      is contradictory. However, balancing the benefits and low side effects associated
      with haloperidol prophylaxis, this preventive intervention may be useful to
      reduce the incidence of delirium in critically ill adults in intensive care
      units.

PMID- 28498177
TI  - Effectiveness of topical skin products in the treatment and prevention of
      incontinence-associated dermatitis: a systematic review.
AB  - BACKGROUND: Incontinence-associated dermatitis (IAD) is inflammation of the skin
      resulting from repeated contact with urine and/or feces. It causes pain, redness,
      swelling and excoriation, and may lead to complications such as fungal skin
      infections and pressure injuries. It is important to prevent and treat IAD to
      avoid complications and improve patient outcomes. A number of products are
      available for protecting skin, but evidence on their effectiveness is limited.
      OBJECTIVES: The current review aimed to establish the effectiveness of topical
      skin products in reducing the occurrence and/or severity of IAD. INCLUSION
      CRITERIA TYPES OF PARTICIPANTS: Adult patients over the age of 18 years with
      incontinence and/or diarrhea. TYPES OF INTERVENTION: Topical skin products as
      individual interventions or part of a skin care regimen. TYPES OF STUDIES: Both
      published and unpublished study designs including randomized controlled trials,
      non-randomized controlled trials, quasi-experimental, before and after,
      prospective and retrospective cohort, case-control, analytical cross-sectional,
      descriptive study designs including case series, individual case reports and
      descriptive cross-sectional studies across all care settings for inclusion.
      OUTCOMES: The primary outcome of interest was the absence or non-development,
      reduction or resolution, new development or increase in the occurrence of IAD or
      the increase in severity of IAD. The secondary outcome was any adverse effect
      caused by the skin care products used. SEARCH STRATEGY: A three-step search
      strategy to find both published and unpublished papers was utilized in this
      review. Studies were limited to those published in English from 1980 to 2016.
      METHODOLOGICAL QUALITY: Papers selected were assessed by two independent
      reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics
      Assessment and Review Instrument (JBI-MAStARI). DATA EXTRACTION: Data were
      extracted using the standardized data extraction tool in JBI-MAStARI. The data
      extracted included specific details about the interventions, populations, study
      methods and outcomes. DATA SYNTHESIS: Studies were assessed for methodological
      quality and statistical significance to determine validity and generalizability
      of study results. It was not possible to pool studies to conduct meta-analysis or
      test for heterogeneity. RESULTS: There were a limited number of clinical trials
      that compared products for efficacy in preventing and treating IAD. Assessment
      tools and severity scores used to measure skin damage outcomes were dissimilar
      and prone to subjectivity. It was difficult to ascertain superiority of any
      individual product. CONCLUSION: Information on barrier protective efficacy, side
      effects and cost can be valuable to both clinicians and care providers. More
      randomized controlled trials on product effectiveness for prevention and
      treatment of IAD are highly recommended.

PMID- 28498178
TI  - Supporting Implementation Research to Improve Coverage and Uptake of HIV Related
      Interventions.
AB  - In 2015, Global Affairs Canada joined other members of the United Nations to
      establish the Sustainable Development Goals, which include the elimination of
      AIDS by 2030. Innovation is an important part of accelerating the response
      against HIV and ensuring success in eliminating AIDS by 2030. This is the reason
      Global Affairs Canada decided to partner with the World Health Organization, to
      support the INtegration and Scaling Up PMTCT through Implementation REsearch
      (INSPIRE) initiative, to learn how HIV interventions can be successfully
      integrated with other essential health services for mothers and children,
      especially among the most vulnerable populations. Canada also believes that the
      empowerment of women and girls will be critical to eliminating AIDS. INSPIRE is
      the evidence that providing women with the knowledge and skills necessary to
      prevent, treat, and manage HIV enables them to become experts and agents of
      change in their families and communities. We know that when women are empowered
      with critical information regarding their health, there is greater retention in
      care which leads to improved treatment adherence and ultimately helps to reduce
      the rate of new infections. Global Affairs Canada is proud to have supported the
      World Health Organization in this effort.

PMID- 28498179
TI  - Improving Retention in Care Among Pregnant Women and Mothers Living With HIV:
      Lessons From INSPIRE and Implications for Future WHO Guidance and Monitoring.
AB  - Identifying women living with HIV, initiating them on lifelong antiretroviral
      treatment (ART), and retaining them in care are among the important challenges
      facing this generation of health care managers and public health researchers.
      Implementation research attempts to solve a wide range of implementation problems
      by trying to understand and work within real-world conditions to find solutions
      that have a measureable impact on the outcomes of interest. Implementation
      research is distinct from clinical research in many ways yet demands similar
      standards of conceptual thinking and discipline to generate robust evidence that
      can be, to some extent, generalized to inform policy and service delivery. In
      2011, the World Health Organization (WHO), with funding from Global Affairs
      Canada, began support to 6 implementation research projects in Malawi, Nigeria,
      and Zimbabwe. All focused on evaluating approaches for improving rates of
      retention in care among pregnant women and mothers living with HIV and ensuring
      their continuation of ART. This reflected the priority given by ministries of
      health, program implementers, and researchers in each country to the importance
      of women living with HIV returning to health facilities for routine care,
      adherence to ART, and improved health outcomes. Five of the studies were cluster
      randomized controlled trials, and 1 adopted a matched cohort design. Here, we
      summarize some of the main findings and key lessons learned. We also consider
      some of the broader implications, remaining knowledge gaps, and how
      implementation research is integral to, and essential for, global guideline
      development and to inform HIV/AIDS strategies.

PMID- 28498180
TI  - Beyond "Option B+": Understanding Antiretroviral Therapy (ART) Adherence,
      Retention in Care and Engagement in ART Services Among Pregnant and Postpartum
      Women Initiating Therapy in Sub-Saharan Africa.
AB  - BACKGROUND: Several studies from sub-Saharan Africa have highlighted significant
      challenges in providing antiretroviral therapy (ART) to pregnant and postpartum
      women, with specific concerns around maintaining optimal levels of adherence to
      ART and/or retaining women in long-term services. However, there are few
      conceptual frameworks to help understand nonadherence and nonretention, as well
      as the drivers of these, among HIV-infected women, particularly in the postpartum
      period. METHODS: This review provides an overview of the key issues involved in
      thinking about ART adherence, retention in care and engagement in ART services
      among pregnant and postpartum women. RESULTS: The related behaviors of adherence
      and retention may be understood as components of effective engagement of patients
      in ART services, which share the goal of achieving and maintaining suppressed
      maternal viral load on ART. Under this framework, the existing literature
      indicates that disengagement from care is widespread among postpartum women, with
      strikingly similar data emerging from ART services around the globe and
      indications that similar challenges may be encountered by postpartum care
      services outside the context of HIV. However, the drivers of disengagement
      require further research, and evidence-based intervention strategies are limited.
      CONCLUSIONS: The challenges of engaging women in ART services during pregnancy
      and the postpartum period seem pervasive, although the determinants of these are
      poorly understood. Looking forward, a host of innovative intervention approaches
      are needed to help improve women's engagement, and in turn, promote maternal and
      child health in the context of HIV.

PMID- 28498181
TI  - Impact of Mother-Infant Pair Clinics and Short-Text Messaging Service (SMS)
      Reminders on Retention of HIV-Infected Women and HIV-Exposed Infants in eMTCT
      Care in Malawi: A Cluster Randomized Trial.
AB  - BACKGROUND: Poor retention of mothers and HIV-exposed infants (HEIs) in HIV care
      threatens efforts to eliminate pediatric HIV. Novel strategies are required to
      address this challenge. We compared 12-month maternal and HEI postpartum
      retention in health facilities implementing the following HIV care delivery
      models: integrated HIV and maternal, neonatal, and child health services [mother
      infant pair (MIP) clinics], MIP clinics plus short-text messaging service (SMS)
      reminders to prevent default (MIP + SMS), and standard of care (SOC). METHODS:
      From May 2013 to August 2016, a cluster randomized trial was conducted in rural
      Malawi, which randomized 30 health facilities to the 3 service delivery models.
      HIV+ pregnant women and HEIs were enrolled and followed up to monitor compliance
      with prescheduled visits and retention. Log binomial regression, using
      generalized estimated equation, was used to assess the impact of the models on
      retention. RESULTS: The trial enrolled 461, 493, and 396 HIV+ pregnant women and
      386, 399, and 300 HEIs into the MIP, MIP + SMS, and SOC arms, respectively.
      Compared with the 12-month maternal retention rate in the SOC arm (22.2%), the
      rates were similar in the MIP arm [19.3%, risk ratio (RR): 0.85, 95% confidence
      interval (CI): 0.56 to 1.30] and in the MIP + SMS arm (24.9%, RR: 1.08, 95% CI:
      0.87 to 1.35). Compared with the 12-month infant retention rate in the SOC arm
      (9.8%), the rates were similar in the MIP arm (8.0%, RR: 0.89, 95% CI: 0.31 to
      2.58) and in the MIP + SMS arm (19.5%, RR: 1.40, 95% CI: 0.85 to 2.31).
      CONCLUSIONS: MIP and MIP + SMS service delivery models were ineffective in
      improving maternal and infant retention in rural Malawi.

PMID- 28498182
TI  - Integrating HIV and Maternal, Neonatal and Child Health Services in Rural Malawi:
      An Evaluation of the Implementation Processes and Challenges.
AB  - INTRODUCTION: Introducing Option B+ in Malawi increased antiretroviral therapy
      coverage among pregnant and breastfeeding women 3 fold. The Promoting Retention
      among Infants and Mothers Effectively (PRIME) study integrated care of Maternal,
      Neonatal and Child Health services through a mother-infant pair (MIP) clinic.
      This article evaluates the implementation processes and challenges health care
      workers' experienced in implementing these MIP clinics. METHODS: Between May 2013
      and August 2016, 20 health facilities implemented MIP clinics. Health care
      workers' performance implementing MIP clinics was assessed through a mentorship
      score from 0 to 5 and supplemented with qualitative data from mentorship reports.
      Visit alignment of participants' appointment and attendance dates with MIP clinic
      dates were calculated and summarized by overall proportions among all patient
      visits. RESULTS: The average mentorship score was 3.8, improving from 3.0 to 4.2
      from quarter one 2015 to quarter one 2016. Proportions of maternal and infant
      appointment dates that aligned with MIP clinic dates were 47.0% and 5.9%, with
      greatest improvement between 2013 and 2015. Proportions of maternal and infant
      attendance dates that aligned with MIP clinic dates were 41.7% and 51.2% and
      improved over time. DISCUSSION: Despite improvement in staff mentorship scores,
      many MIPs were not exposed to integrated HIV and Maternal, Neonatal and Child
      Health services offered through MIP clinics primarily because of clinic
      scheduling challenges. To improve utilization of integrated MIP clinics, careful
      design of a delivery approach is needed that is acceptable to clinic staff,
      addresses local realities, and includes appropriate investment and oversight.

PMID- 28498183
TI  - Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake
      and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child
      Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi).
AB  - BACKGROUND: Many sub-Saharan African countries have adopted Option B+, a
      prevention of mother-to-child transmission approach providing HIV-infected
      pregnant and lactating women with immediate lifelong antiretroviral therapy. High
      maternal attrition has been observed in Option B+. Peer-based support may improve
      retention. METHODS: A 3-arm stratified cluster randomized controlled trial was
      conducted in Malawi to assess whether facility- and community-based peer support
      would improve Option B+ uptake and retention compared with standard of care
      (SOC). In SOC, no enhancements were made (control). In facility-based and
      community-based models, peers provided patient education, support groups, and
      patient tracing. Uptake was defined as attending a second scheduled follow-up
      visit. Retention was defined as being alive and in-care at 2 years without
      defaulting. Attrition was defined as death, default, or stopping antiretroviral
      therapy. Generalized estimating equations were used to estimate risk differences
      (RDs) in uptake. Cox proportional hazards regression with shared frailties was
      used to estimate hazard of attrition. RESULTS: Twenty-one facilities were
      randomized and enrolled 1269 women: 447, 428, and 394 in facilities that
      implemented SOC, facility-based, and community-based peer support models,
      respectively. Mean age was 27 years. Uptake was higher in facility-based (86%;
      RD: 6%, confidence interval [CI]: -3% to 15%) and community-based (90%; RD: 9%,
      CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher
      in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD:
      16%, CI: 3% to 30%) models compared with SOC (66%). CONCLUSIONS: Facility- and
      community-based peer support interventions can benefit maternal uptake and
      retention in Option B+.

PMID- 28498184
TI  - Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's
      Option B+ Program: Results From the PURE Malawi Study.
AB  - BACKGROUND: In 2011, Malawi launched Option B+, a program of universal
      antiretroviral therapy (ART) treatment for pregnant and lactating women to
      optimize maternal health and prevent pediatric HIV infection. For optimal
      outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA
      suppression and HIV drug resistance in the PURE study. METHODS: PURE study was a
      cluster-randomized controlled trial evaluating 3 strategies for promoting uptake
      and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3:
      Community Peer support. Pregnant and breastfeeding mothers were enrolled and
      followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing
      were collected at 6 months. Samples with ART failure (HIVRNA >=1000 copies/ml)
      had resistance testing. We calculated odds ratios for ART failure using
      generalized estimating equations with a logit link and binomial distribution.
      RESULTS: We enrolled 1269 women across 21 sites in Southern and Central Malawi.
      Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months,
      950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and
      699/833 (84%) were suppressed. Among those with HIVRNA >=1000 copies/ml with
      successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml),
      confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside
      reverse transcriptase inhibitor class of drugs. ART failure was associated with
      treatment default but not study arm, age, WHO stage, or breastfeeding status.
      CONCLUSIONS: Virologic suppression at 6 months was <90% target, but the observed
      confirmed resistance rates suggest that adherence support should be the primary
      approach for early failure in option B+.

PMID- 28498185
TI  - The Effect of a Continuous Quality Improvement Intervention on Retention-In-Care
      at 6 Months Postpartum in a PMTCT Program in Northern Nigeria: Results of a
      Cluster Randomized Controlled Study.
AB  - BACKGROUND: Retention in care is critical for improving HIV-infected maternal
      outcomes and reducing vertical transmission. Health systems' interventions such
      as continuous quality improvement (CQI) may support health services to address
      factors that affect the delivery of HIV-related care and thereby influence rates
      of retention-in-care. METHODOLOGY: We evaluated the effect of a CQI intervention
      on retention-in-care at 6 months postpartum of pregnant women and mothers living
      with HIV who had been started on lifelong antiretroviral treatment. Thirty-two
      health care facilities were randomized to either implement the intervention or
      not. We considered women fully retained in care when they attended the 6-month
      postpartum visit and did not miss any previous scheduled visit by more than 30
      days. RESULTS: Five hundred eleven women living with HIV attending antenatal
      clinics at 26 facilities were included in the analysis. Median age at enrolment
      was 27 years and gestational age was 20 weeks. Seventy-one percent of women were
      seen at 6-month postpartum irrespective of missing any scheduled visit. However,
      43% of women were fully retained at 6-month postpartum and did not miss any
      scheduled visit based on our stringent study definition of retention. There was
      no significant difference in retention at 6 months between the intervention and
      control arms [44% vs. 41%, relative risk: 1.08; 95% confidence interval (CI):
      0.78 to 1.49]. Initiation of ARV prophylaxis among infants within 72 hours was
      not different by study arm (66.0% vs. 74.7%, relative risk = 0.95; 95% CI: 0.84
      to 1.07) but rates of early infant testing at 4-6 weeks were higher in
      intervention sites (48.8% vs. 25.3%, adjusted relative risk: 1.76; 95% CI: 1.27
      to 2.42). CONCLUSIONS: CQI as implemented in this study did not differ across
      study arms in the rates of retention. Several intervention design or
      implementation issues or other contextual constraints may explain the absence of
      effect.

PMID- 28498186
TI  - Using Small Tests of Change to Improve PMTCT Services in Northern Nigeria:
      Experiences From Implementation of a Continuous Quality Improvement and
      Breakthrough Series Program.
AB  - BACKGROUND: Continuous Quality Improvement (CQI) is a process where health teams
      systematically collect and regularly reflect on local data to inform decisions
      and modify local practices and so improve delivery of services. We implemented a
      cluster randomized trial to examine the effects of CQI interventions on
      Prevention of Mother-to-Child Transmission (PMTCT) services. Here, we report our
      experiences and challenges establishing CQI in 2 high HIV prevalence states in
      northern Nigeria. METHODS: Facility-based teams were trained to implement CQI
      activities, including structured assessments, developing change packages, and
      participation in periodic collaborative learning sessions. Locally evolved
      solutions (change ideas) were tested and measured using process data and
      intermediate process indicators were agreed including overall time spent
      accessing services, client satisfaction, and quality of data. RESULTS: Health
      workers actively participated in clinic activities and in the collaborative
      learning sessions. During the study, the mean difference in time spent accessing
      services during clinic visits increased by 40 minutes (SD = 93.4) in the control
      arm and decreased by 44 minutes (SD = 73.7) in the intervention arm. No
      significant difference was recorded in the mean client satisfaction assessment
      score by study arm. The quality of data was assessed using a standardized tool
      scored out of 100; compared with baseline data, quality at the end of study had
      improved at intervention sites by 6 points (95% CI: 2.0 to 10.1). CONCLUSIONS:
      Health workers were receptive to CQI process. A compendium of "change ideas"
      compiled into a single change package can be used to improve health care
      delivery.

PMID- 28498187
TI  - The Impact of Structured Mentor Mother Programs on 6-Month Postpartum Retention
      and Viral Suppression among HIV-Positive Women in Rural Nigeria: A Prospective
      Paired Cohort Study.
AB  - BACKGROUND: Peer support (PS) has reportedly improved Prevention of mother-to
      child transmission (PMTCT) outcomes in high HIV-burden settings; however,
      evidence of impact on retention in care is limited. Retention in care implies
      consistent engagement and treatment adherence. The MoMent study evaluated the
      impact of structured vs unstructured PS on postpartum retention and viral load
      suppression among rural Nigerian women. METHODS: A total of 497 HIV-positive
      pregnant women were consecutively enrolled at 10 primary health care centers with
      structured mentor mother (MM) support, and at 10 pair-matched primary health care
      centers with routine, ad hoc PS. The structured MM intervention comprised an
      outcome-specific scope of work, close MM supervision, standardized documentation,
      performance evaluations, and retraining as appropriate. Retention was defined by
      clinic attendance during the first 6-month postpartum. Participants with >=3 of 6
      expected monthly visits were considered retained. Women with a 6-month postpartum
      plasma viral load of <20 copies/mL were considered suppressed. A logistic
      regression model with generalized estimating equation was used to assess the
      effect of MMs on retention and viral suppression. RESULTS: Exposure to structured
      MM support was associated with higher odds of retention than routine PS (adjusted
      odds ratio = 5.9, 95% confidence interval: 3.0 to 11.6). Similarly, the odds of
      viral suppression at 6-month postpartum were higher for MM-supported women
      (adjusted odds ratio = 4.9, 95% confidence interval: 2.6 to 9.2). CONCLUSIONS:
      Structured PS significantly improved postpartum PMTCT retention and viral
      suppression rates among women in rural Nigeria. Introduction of structure can
      enhance the impact of PS interventions on PMTCT outcomes.

PMID- 28498188
TI  - The Impact of Structured Mentor Mother Programs on Presentation for Early Infant
      Diagnosis Testing in Rural North-Central Nigeria: A Prospective Paired Cohort
      Study.
AB  - BACKGROUND: Early infant diagnosis (EID) by 2 months of age is an important
      prevention of mother-to-child cascade step that serves as an early postpartum
      indicator of program success. Uptake and timely presentation for infant HIV
      diagnosis are significant challenges in resource-limited settings. Few studies on
      maternal peer support (PS) have demonstrated impact on EID. The MoMent study
      evaluated the impact of structured PS on timely presentation for EID testing in
      rural North-Central Nigeria. METHODS: A total of 497 HIV-positive pregnant women
      were consecutively recruited at 10 primary health care centers with structured,
      closely supervised Mentor Mother (MM) support, and 10 pair-matched primary health
      care centers with routine but ad hoc PS. EID was assessed among HIV-exposed
      infants delivered to recruited women, and was defined by presentation for DNA
      polymerase chain reaction testing between 35 and 62 days of life. A logistic
      regression model with generalized estimating equation to account for clustering
      was used to assess the effect of MMs on EID presentation. RESULTS: Data from 408
      live-born infants were available for analysis. Exposure to MM support was
      associated with higher odds of timely EID presentation among infants, compared
      with routine PS (adjusted odds ratios = 3.7, 95% confidence interval: 2.8 to
      5.0). CONCLUSIONS: Closely supervised, organized MM support significantly
      improved presentation for EID among HIV-exposed infants in a rural Nigerian
      setting. Structured PS can improve rates of timely EID presentation and
      potentially the uptake of EID testing in resource-limited settings.

PMID- 28498189
TI  - Impact of Point-of-Care CD4 Testing on Retention in Care Among HIV-Positive
      Pregnant and Breastfeeding Women in the Context of Option B+ in Zimbabwe: A
      Cluster Randomized Controlled Trial.
AB  - INTRODUCTION: Scale-up of Option B+ in Zimbabwe has increased antiretroviral
      therapy (ART) coverage but patient loss-to-follow-up remains high; thus,
      effective strategies to improve retention in care are needed. Evidence for
      Elimination, a cluster randomized controlled trial, evaluated the impact of point
      of-care (POC) CD4 testing with CD4 count-specific adherence counseling on rates
      of retention among 1150 HIV-positive pregnant women initiating ART in Zimbabwe.
      METHODS: Thirty-two primary care health facilities were randomized to offer
      either standard-of-care (SOC) or POC CD4 testing plus CD4-specific counseling to
      clients (POC Plus). The primary outcome was the proportion of HIV-positive
      pregnant women retained on ART after 12 months, calculated by cluster-adjusted
      proportions, unadjusted and adjusted relative risks (RR and aRR, respectively).
      RESULTS: Retention in care 12 months after initiation was 50.7% and 54.5% in the
      POC Plus and SOC arms, respectively (RR 0.93, 95% confidence interval [CI]: 0.78
      to 1.11; aRR 0.91, 95% CI: 0.77 to 1.07). Although considered not retained, 9.7%
      transferred to another facility and 0.2% died. Most women, 95.3% in POC Plus and
      92.9% in SOC, initiated ART within 1 month of antenatal booking (RR 1.03, 95% CI:
      0.97 to 1.08). DISCUSSION: Although patient retention was similar in both arms,
      women in the POC Plus arm were more likely to have received a CD4 test at booking
      and a repeat CD4 test later in care. CD4 is no longer required for treatment
      initiation but is still recommended in national guidelines and is of value in
      clinical management. Further work is needed to identify effective strategies to
      increase patient retention in ART care.

PMID- 28498190
TI  - Patterns of HIV Care Clinic Attendance and Adherence to Antiretroviral Therapy
      Among Pregnant and Breastfeeding Women Living With HIV in the Context of Option
      B+ in Zimbabwe.
AB  - BACKGROUND: Consistent use of antiretroviral therapy (ART) during pregnancy and
      breastfeeding reduces the likelihood of mother-to-child HIV transmission. All
      pregnant and breastfeeding women living with HIV in Zimbabwe are offered ART with
      same-day initiation regardless of CD4 count (Option B+). We investigated patterns
      of clinic attendance and adherence to ART among HIV-infected pregnant women in
      Zimbabwe. METHODS: The Evidence for Elimination cluster-randomized trial
      evaluating point-of-care CD4 testing included 1150 HIV-infected ART-naive women
      attending antenatal care between January 2014 and June 2015. Thirty-two primary
      care facilities were randomized between 2 arms. In this secondary analysis of
      Evidence for Elimination data collected from routine clinic records, we
      classified women by number of pills dispensed, and estimated adherence from the
      ratio of pills to days since ART initiation (Medication Possession Ratio,
      adherent if >=95%) or the period when they stopped receiving medication. RESULTS:
      Two-thirds (67.7%) were still receiving medication 1 year after initiation; less
      than half of the cohort (39.1%) were adherent. Younger women, newly diagnosed
      with HIV, and/or first presenting to antenatal care in their third trimester were
      more likely to drop from care or be nonadherent 360 days after ART initiation.
      CONCLUSION: Adherence to ART is suboptimal particularly among young, newly
      diagnosed, and/or late presenting patients. Interventions that target these
      groups, as well as provide additional support to all women who are newly
      diagnosed, may improve Option B+ ART care. More information is needed about the
      barriers to ART care among late presenters and teenagers.

PMID- 28498191
TI  - Impact of Facility-Based Mother Support Groups on Retention in Care and PMTCT
      Outcomes in Rural Zimbabwe: The EPAZ Cluster-Randomized Controlled Trial.
AB  - BACKGROUND: Prevention of mother-to-child transmission elimination goals are
      hampered by low rates of retention in care. The Eliminating Paediatric AIDS in
      Zimbabwe project assessed whether mother support groups (MSGs) improve rates of
      retention in care of HIV-exposed infants and their HIV-positive mothers, and
      maternal and infant outcomes. METHODS: The study involved 27 rural clinics in
      eastern Zimbabwe. MSGs were established in 14 randomly selected clinics and met
      every 2 weeks coordinated by volunteer HIV-positive mothers. MSG coordinators
      provided health education and reminded mothers of MSG meetings by cell phone.
      Infant retention in care was defined as "12 months postpartum point attendance"
      at health care visits of HIV-exposed infants at 12 months of age. We also
      measured regularity of attendance and other program indicators of HIV-positive
      mothers and their HIV-exposed infants. RESULTS: Among 507 HIV-positive pregnant
      women assessed as eligible, 348 were enrolled and analyzed (69%) with mothers who
      had disclosed their HIV status being overrepresented. In the intervention arm,
      69% of infants were retained in care at 12 months versus 61% in the control arm,
      with no statistically significant difference. Retention and other program
      outcomes were systematically higher in the intervention versus control arm,
      suggesting trends toward positive health outcomes with exposure to MSGs.
      DISCUSSION: We were unable to show that facility-based MSGs improved retention in
      care at 12 months among HIV-exposed infants. Selective enrollment of mothers more
      likely to be retained-in-care may have contributed to lack of effect. Methods to
      increase the impact of MSGs on retention including targeting of high-risk mothers
      are discussed.

PMID- 28498192
TI  - Patterns of Attendance at Mother Support Groups in Zimbabwe. The EPAZ Trial (2014
      2016).
AB  - BACKGROUND: In Southern Africa, groups of mothers living with HIV successfully
      provide peer psychosocial support during pregnancy and early childhood. We report
      patterns of attendance at Mother Support Groups (MSGs) sessions among women and
      mothers living with HIV in rural Zimbabwe. METHODS: In the Elimination of
      Pediatric AIDS cluster-randomized trial, MSGs were established in 14 health
      facilities in Mutare and Makoni districts. Patterns of attendance at MSG sessions
      were categorized by calendar attendance from delivery to 6-month postpartum using
      a Dynamic Time Warping clustering method. Baseline characteristics of women and
      postpartum MSG attendance patterns were described. Linkages between these
      patterns and 12-month postpartum retention in care were explored using mixed
      effects models. RESULTS: Most women (88%) attended at least 1 MSG session between
      enrollment and 6-month postpartum. Two patterns of postpartum MSG attendance,
      "Regular Attendance" and "Non-Regular Attendance," were readily identified. Being
      older than 32 (P = 0.01), booking for antenatal care before 22 weeks gestational
      age (P = 0.02), and being on antiretroviral therapy at first antenatal care
      booking (P = 0.01) were significantly associated with "Regular Attendance."
      "Regular Attendance" at MSG sessions during the 6-month postpartum period was
      significantly associated with better retention in care at 12 months, compared
      with "Non-Regular Attendance" (P < 0.01). DISCUSSION: Women living with HIV
      attended MSG sessions. However, few attended regularly. Younger and newly
      diagnosed women were less likely to attend postpartum MSG sessions or remain in
      care at 12 months postpartum. Peer support models should consider specific needs
      of these women, especially in rural areas, in order for MSGs to contribute to
      improve maternal and child health outcomes.

PMID- 28498193
TI  - The Roles of Expert Mothers Engaged in Prevention of Mother-to-Child Transmission
      (PMTCT) Programs: A Commentary on the INSPIRE Studies in Malawi, Nigeria, and
      Zimbabwe.
AB  - INTRODUCTION: Several initiatives aiming to improve retention and adherence in
      Prevention of Mother-to-Child Transmission of HIV (PMTCT) programs include
      "expert mothers" (EMs) as a central tenet of their interventions. This article
      compares the role of EMs in 3 implementation research studies examining
      approaches for improving retention in care among mothers living with HIV.
      METHODS: We compared and synthesized qualitative data and lessons learned from 3
      studies (MoMent in Nigeria, PURE in Malawi, and EPAZ in Zimbabwe) with respect to
      the involvement of EMs in supporting PMTCT clients. The frame of reference for
      the comparison is the role that EMs play in PMTCT service delivery for
      individuals, at the health facility, within the health system, and in the
      community. RESULTS: EMs' role was positively perceived by PMTCT clients and
      health care workers, as EMs provided an expanded range of services directly
      benefiting clients and enabling health care workers to share their workload.
      Common challenges included difficulties in reaching male partners and fear of
      stigma. The lack of structure and standardization in EM interventions in relation
      to eligibility criteria, training, certification, and remuneration were
      identified as important barriers to EMs' role development within existing health
      systems. CONCLUSIONS: The role of EMs within PMTCT programs continues to expand
      rapidly. There is a need for coordinated action to develop shared standards and
      principles commensurate with the new roles and additional demands placed on EMs
      to support PMTCT services, including EM certification, mentoring and supervision
      standards, standardized PMTCT-specific training curricula, and, where
      appropriate, agreed remuneration rates.

PMID- 28498194
TI  - Modeling the Impact of Retention Interventions on Mother-to-Child Transmission of
      HIV: Results From INSPIRE Studies in Malawi, Nigeria, and Zimbabwe.
AB  - BACKGROUND: Six implementation research studies in Malawi, Nigeria, and Zimbabwe
      tested approaches for improving retention in care among women living with HIV. We
      simulated the impact of their interventions on the probability of HIV
      transmission during pregnancy and breastfeeding. METHODS: A computer-based state
      transition model was developed to estimate the impact of the retention
      interventions. Patient-level data from the 6 studies were aggregated and
      analyzed, and weighted averages of mother-to-child transmission (MTCT) of HIV
      probabilities were presented. The average MTCT probability of the more successful
      interventions was applied to national estimates to calculate potential infections
      averted if these interventions were taken to scale. RESULTS: Among the total
      cohort of 5742 HIV-positive women, almost 80% of all infant infections are
      attributed to the roughly 20% of HIV-positive pregnant and breastfeeding women
      not retained on antiretroviral therapy. Higher retention in the arms receiving
      interventions resulted in an overall lower estimated MTCT probability of 9.9%
      compared with 12.3% in the control arms. In the 2 studies that showed a
      statistically significant effect, Prevention of MTCT Uptake and Retention (PURE)
      and Mother Mentor (MoMent), the difference in transmission rates between
      intervention and control arms was 4.1% and 7.3%, respectively. Scaling up
      retention interventions nationally in the 3 countries could avert an average of
      almost 3000 infant infections annually. CONCLUSIONS: Linking HIV-positive
      pregnant women to antiretroviral therapy and retaining them is essential for
      addressing the remaining gaps and challenges in HIV/AIDS care and the elimination
      of MTCT. At national level, even modest improvements in retention translates into
      large numbers of infant infections averted.

PMID- 28498195
TI  - Building Health System Capacity Through Implementation Research: Experience of
      INSPIRE-A Multi-country PMTCT Implementation Research Project.
AB  - BACKGROUND: The INSPIRE-Integrating and Scaling Up PMTCT through Implementation
      REsearch-initiative was established as a model partnership of national prevention
      of mother-to-child transmission of HIV (PMTCT) implementation research in 3 high
      HIV burden countries-Malawi, Nigeria, and Zimbabwe. INSPIRE aimed to link local
      research groups with Ministries of Health (MOH), build local research capacity,
      and demonstrate that implementation research may contribute to improving health
      care delivery and respond to program challenges. METHODOLOGY: We used a mixed
      methods approach to review capacity building activities, as experienced by health
      care workers, researchers, and trainers conducted in the 6 INSPIRE projects
      before and during study implementation. RESULTS: Between 2011 and 2016, over 3400
      health care workers, research team members, and community members participated in
      INSPIRE activities. This included research prioritization exercises, proposal
      development, good clinical practice and research ethics training, data management
      and analysis workshops, and manuscript development. Health care workers in
      clinics and district health offices acknowledged the value of hosting
      implementation research projects and how the quality of services improved.
      Research teams acknowledged the opportunities that projects provided for personal
      development and the value of participating in a multicountry research network.
      DISCUSSION: INSPIRE provided an opportunity for African-led research in which
      researchers worked closely with national MOH to identify priority research
      questions and implement studies. Close partnerships between research teams and
      local implementers facilitated project responsiveness to local program issues.
      Consequently, processes and training needed for study implementation also
      improved local program management and service delivery. Additional benefits
      included improved data management, publications, and career development.

PMID- 28498196
TI  - Identifying Increased Risk of Readmission and In-hospital Mortality Using
      Hospital Administrative Data: The AHRQ Elixhauser Comorbidity Index.
AB  - OBJECTIVE: We extend the literature on comorbidity measurement by developing 2
      indices, based on the Elixhauser Comorbidity measures, designed to predict 2
      frequently reported health outcomes: in-hospital mortality and 30-day readmission
      in administrative data. The Elixhauser measures are commonly used in research as
      an adjustment factor to control for severity of illness. DATA SOURCES: We used a
      large analysis file built from all-payer hospital administrative data in the
      Healthcare Cost and Utilization Project State Inpatient Databases from 18 states
      in 2011 and 2012. METHODS: The final models were derived with bootstrapped
      replications of backward stepwise logistic regressions on each outcome. Odds
      ratios and index weights were generated for each Elixhauser comorbidity to create
      a single index score per record for mortality and readmissions. Model validation
      was conducted with c-statistics. RESULTS: Our index scores performed as well as
      using all 29 Elixhauser comorbidity variables separately. The c-statistic for our
      index scores without inclusion of other covariates was 0.777 (95% confidence
      interval, 0.776-0.778) for the mortality index and 0.634 (95% confidence
      interval, 0.633-0.634) for the readmissions index. The indices were stable across
      multiple subsamples defined by demographic characteristics or clinical condition.
      The addition of other commonly used covariates (age, sex, expected payer)
      improved discrimination modestly. CONCLUSIONS: These indices are effective
      methods to incorporate the influence of comorbid conditions in models designed to
      assess the risk of in-hospital mortality and readmission using administrative
      data with limited clinical information, especially when small samples sizes are
      an issue.

PMID- 28498198
TI  - Development of a Risk-adjustment Model for the Inpatient Rehabilitation Facility
      Discharge Self-care Functional Status Quality Measure.
AB  - BACKGROUND: Functional status measures are important patient-centered indicators
      of inpatient rehabilitation facility (IRF) quality of care. We developed a risk
      adjusted self-care functional status measure for the IRF Quality Reporting
      Program. This paper describes the development and performance of the measure's
      risk-adjustment model. METHODS: Our sample included IRF Medicare fee-for-service
      patients from the Centers for Medicare & Medicaid Services' 2008-2010 Post-Acute
      Care Payment Reform Demonstration. Data sources included the Continuity
      Assessment Record and Evaluation Item Set, IRF-Patient Assessment Instrument, and
      Medicare claims. Self-care scores were based on 7 Continuity Assessment Record
      and Evaluation items. The model was developed using discharge self-care score as
      the dependent variable, and generalized linear modeling with generalized
      estimation equation to account for patient characteristics and clustering within
      IRFs. Patient demographics, clinical characteristics at IRF admission, and
      clinical characteristics related to the recent hospitalization were tested as
      risk adjusters. RESULTS: A total of 4769 patient stays from 38 IRFs were
      included. Approximately 57% of the sample was female; 38.4%, 75-84 years; and
      31.0%, 65-74 years. The final model, containing 77 risk adjusters, explained
      53.7% of variance in discharge self-care scores (P<0.0001). Admission self-care
      function was the strongest predictor, followed by admission cognitive function
      and IRF primary diagnosis group. The range of expected and observed scores
      overlapped very well, with little bias across the range of predicted self-care
      functioning. CONCLUSIONS: Our risk-adjustment model demonstrated strong validity
      for predicting discharge self-care scores. Although the model needs validation
      with national data, it represents an important first step in evaluation of IRF
      functional outcomes.

PMID- 28498199
TI  - Incorporating Alternative Care Site Characteristics Into Estimates of
      Substitutable ED Visits.
AB  - BACKGROUND: Several recent efforts to improve health care value have focused on
      reducing emergency department (ED) visits that potentially could be treated in
      alternative care sites (ie, primary care offices, retail clinics, and urgent care
      centers). Estimates of the number of these visits may depend on assumptions
      regarding the operating hours and functional capabilities of alternative care
      sites. However, methods to account for the variability in these characteristics
      have not been developed. OBJECTIVE: To develop methods to incorporate the
      variability in alternative care site characteristics into estimates of ED visit
      "substitutability." RESEARCH DESIGN, SUBJECTS, AND MEASURES: Our approach uses
      the range of hours and capabilities among alternative care sites to estimate
      lower and upper bounds of ED visit substitutability. We constructed "basic" and
      "extended" criteria that captured the plausible degree of variation in each
      site's hours and capabilities. To illustrate our approach, we analyzed data from
      22,697 ED visits by adults in the 2011 National Hospital Ambulatory Medical Care
      Survey, defining a visit as substitutable if it was treat-and-release and met
      both the operating hours and functional capabilities criteria. RESULTS: Use of
      the combined basic hours/basic capabilities criteria and extended hours/extended
      capabilities generated lower and upper bounds of estimates. Our criteria
      classified 5.5%-27.1%, 7.6%-20.4%, and 10.6%-46.0% of visits as substitutable in
      primary care offices, retail clinics, and urgent care centers, respectively.
      CONCLUSIONS: Alternative care sites vary widely in operating hours and functional
      capabilities. Methods such as ours may help incorporate this variability into
      estimates of ED visit substitutability.

PMID- 28498197
TI  - Overuse of Health Care Services in the Management of Cancer: A Systematic Review.
AB  - BACKGROUND: Overuse, the provision of health services for which harms outweigh
      the benefits, results in suboptimal patient care and may contribute to the rising
      costs of cancer care. We performed a systematic review of the evidence on overuse
      in oncology. METHODS: We searched Medline, EMBASE, the Cochrane Library, Web of
      Science, SCOPUS databases, and 2 grey literature sources, for articles published
      between December 1, 2011 and March 10, 2017. We included publications from
      December 2011 to evaluate the literature since the inception of the ABIM
      Foundation's Choosing Wisely initiative in 2012. We included original research
      articles quantifying overuse of any medical service in patients with a cancer
      diagnosis when utilizing an acceptable standard to define care appropriateness,
      excluding studies of cancer screening. One of 4 investigator reviewed titles and
      abstracts and 2 of 4 reviewed each full-text article and extracted data.
      Methodology used PRISMA guidelines. RESULTS: We identified 59 articles measuring
      overuse of 154 services related to imaging, procedures, and therapeutics in
      cancer management. The majority of studies addressed adult or geriatric patients
      (98%) and focused on US populations (76%); the most studied services were
      diagnostic imaging in low-risk prostate and breast cancer. Few studies evaluated
      active cancer therapeutics or interventions aimed at reducing overuse. Rates of
      overuse varied widely among services and among studies of the same service.
      CONCLUSIONS: Despite recent attention to overuse in cancer, evidence identifying
      areas of overuse remains limited. Broader investigation, including assessment of
      active cancer treatment, is critical for identifying improvement targets to
      optimize value in cancer care.

PMID- 28498200
TI  - Evaluating the Veterans Choice Program: Lessons for Developing a High-performing
      Integrated Network.

PMID- 28498201
TI  - An Open Letter to the PA Profession.

PMID- 28498202
TI  - Partial Facial Paralysis as a Model for Prophylactic Botulinum Toxin Use for the
      Prevention of Facial Rhytides.

PMID- 28498203
TI  - Superficial CD34-Positive Fibroblastic Tumor Successfully Treated With Mohs
      Micrographic Surgery.

PMID- 28498204
TI  - ASDS Guidelines Task Force: Consensus Recommendations Regarding the Safety of
      Lasers, Dermabrasion, Chemical Peels, Energy Devices, and Skin Surgery During and
      After Isotretinoin Use.
AB  - BACKGROUND: Currently, the isotretinoin (13-cis-retinoic acid) package insert
      contains language advising the discontinuation of isotretinoin for 6 months
      before performing cosmetic procedures, including waxing, dermabrasion, chemical
      peels, laser procedures, or incisional and excisional cold-steel surgery. It is
      common practice to follow this standard because of concerns regarding reports of
      sporadic adverse events and increased risk of scarring. OBJECTIVE: To develop
      expert consensus regarding the safety of skin procedures, including resurfacing,
      energy device treatments, and incisional and excisional procedures, in the
      setting of concurrent or recent isotretinoin use. MATERIALS AND METHODS: The
      American Society for Dermatologic Surgery authorized a task force of content
      experts to review the evidence and provide guidance. First, data were extracted
      from the literature. This was followed by a clinical question review, a consensus
      Delphi process, and validation of the results by peer review. RESULTS: The task
      force concluded that there is insufficient evidence to justify delaying treatment
      with superficial chemical peels and nonablative lasers, including hair removal
      lasers and lights, vascular lasers, and nonablative fractional devices for
      patients currently or recently exposed to isotretinoin. Superficial and focal
      dermabrasion may also be safe when performed by a well-trained clinician.

PMID- 28498205
TI  - In the Toolbox: The Dual Action Nail Clipper.

PMID- 28498206
TI  - Allograft Dermal Matrix for Restoration of Facial Contour Deformities.

PMID- 28498207
TI  - The Kinetics of Reversible Hyaluronic Acid Filler Injection Treated With
      Hyaluronidase.
AB  - BACKGROUND: Hyaluronidase is an enzyme capable of dissolution of hyaluronic acid
      (HA). There is a lack of evidence-based research defining time- and concentration
      dependent reversal of HA filler using hyaluronidase. OBJECTIVE: To explore the
      efficacy of different concentrations of hyaluronidase in digesting commercially
      available HA-based reversible fillers-Belotero Balance (BEL), Juvederm Ultra XC
      (JUVXC), Juvederm Ultra Plus (JUVX+), Juvederm Voluma XC (JUVV), Restylane-L
      (RESL), Restylane Silk (RESS), and Perlane/Restylane Lyft (RESLYFT). MATERIALS
      AND METHODS: This was a blinded randomized study involving 15 participants.
      Participants received HA filler injection into their back, followed by no
      secondary injection, or injection with normal saline, 20 or 40 units of
      hyaluronidase. Using a 5-point palpation scale, the degradation of HA filler was
      monitored over 14 days. RESULTS: In the authors' study, there is a significant
      decrease in HA filler degradation using 20 and 40 units of hyaluronidase compared
      with no secondary injection or normal saline. There is no significant difference
      in HA filler dissolution when comparing 20 to 40 units of hyaluronidase.
      CONCLUSION: Lower concentrations of hyaluronidase may be just as effective as
      higher concentrations to degrade HA filler in situations where the reversal of
      cutaneous augmentation with HA filler arises.

PMID- 28498208
TI  - Transient Nerve Damage After Microfocused Ultrasound With Visualization.

PMID- 28498210
TI  - Repair of a Large Submental Defect.

PMID- 28498209
TI  - Rate of Surgical Site Infections With New Protocol of Prophylactic Antibiotic Use
      in Dermatologic Surgery.

PMID- 28498211
TI  - Sarcoidosis Discovered During Mohs Surgery for Basal Cell Carcinoma.

PMID- 28498212
TI  - ACSM Clinician Profile.

PMID- 28498213
TI  - Thunderstorm Asthma, Relative Anemia, and Football Carnage.

PMID- 28498215
TI  - Brachial Plexopathy.

PMID- 28498216
TI  - When Is It Safe to Run? Applying Four Pain Rules to Running Participation.

PMID- 28498217
TI  - Make Sport Great Again: The Use and Abuse of the Therapeutic Use Exemptions
      Process.

PMID- 28498218
TI  - In Place But Not Always Used: Automated External Defibrillators in Amateur
      Football.

PMID- 28498219
TI  - Premarathon Evaluations: Is There a Role for Runner Prerace Medical Screening and
      Education to Reduce the Risk of Medical Complications?
AB  - There is irrefutable evidence that regular participation in physical activity has
      substantial health benefits, and as such participation in mass community-based
      sports events should be supported. However, with the promotion of physical
      activity comes the potential risk of medical complications during an acute
      exercise session, with this risk varying according to the risk factor profile of
      an individual and the nature of the event. The demographics of marathon race
      entrants changed over the past two to three decades, and currently about 50% of
      runners are older than 40 yr. A consolidated view of previously published
      research shows that in a marathon with a field of 50,000 runners for example, the
      medical staff will, on average, encounter a sudden death every 2 to 3 yr, a
      sudden cardiac arrest every year, 25 runners that present with a serious medical
      complication requiring specialized management or hospitalization, and 1000
      runners that require medical attention. Runners may have several intrinsic risk
      factors that can predispose them to serious acute cardiovascular or other serious
      noncardiac medical complications on race day. This intrinsic risk can be
      exacerbated by several extrinsic risk factors as well. As health care
      professionals, we are obliged to give the best medical advice to individuals who
      wish to participate in moderate- and high-intensity endurance activities, and at
      the same time reduce their risk of a medical complication during exercise.
      Preliminary data indicate that an online prerace medical screening and targeted
      educational intervention program can be successfully implemented and is effective
      in reducing the risk of acute medical complications during a race.

PMID- 28498220
TI  - Patient Presentations and Medical Logistics at Full and Half Ironman Distance
      Triathlons.
AB  - We describe logistical challenges, illness/injury rates, as well as medical and
      ambulance transfer rates (ATR) at an annual large-scale half/full triathlon in a
      remote location. Prospective observational study; registry data. Data on patient
      presentation rates, percentage of patients transferred by ambulance, transfer to
      hospital rates (TTHR), ATR, and medical usage rates were collected and analyzed.
      In total, 1923 athletes participated in the 2016 triathlon (1404 in the full
      length race and 519 in the half) and 181 patient encounters were documented. The
      patient presentation rate (PPR) was 94 in 1000 patients, and 1.6% of patients
      seen onsite required offsite medical care. TTHR and ATR were 1.6 in 1000 and 0.5
      in 1000, respectively. Gastrointestinal issues were the most common presentation
      (50/181; 27.6%), followed by musculoskeletal injury (46/181; 25.4%) and
      nonspecific dizziness (37/181; 20.4%). The incorporation of a coordinated event
      medical plan and team, with integrated on-course and at-finish coverage, may have
      minimized presentations of patients to local health care services; therefore,
      decreasing the effect on the local ambulance service and health infrastructure of
      the host community.

PMID- 28498221
TI  - Optimizing Marathon Race Safety Using an Incident Command Post Strategy.

PMID- 28498222
TI  - Ultrasonic Percutaneous Tenotomy for Recalcitrant Calcific Triceps Tendinosis in
      a Competitive Strongman: A Case Report.

PMID- 28498223
TI  - Bedside Ultrasound Diagnosis of Quadriceps Tendon Rupture and Avulsed Patella.

PMID- 28498224
TI  - Core Training in Low Back Disorders: Role of the Pilates Method.
AB  - The Pilates method is a system of exercises developed by Joseph Pilates, which
      emphasizes recruitment and strengthening of the core muscles, flexibility, and
      breathing, to promote stability and control of movement. Its focus bears
      similarity to current evidence-based exercise programs for low back disorders.
      Spinal stability is a function of three interdependent systems, osseoligamentous,
      muscular, and neural control; exercise addresses both the muscular and neural
      function. The "core" typically refers to the muscular control required to
      maintain functional stability. Prior research has highlighted the importance of
      muscular strength and recruitment, with debate over the importance of individual
      muscles in the wider context of core control. Though developed long before the
      current evidence, the Pilates method is relevant in this setting and clearly
      relates to current evidence-based exercise interventions. Current literature
      supports the Pilates method as a treatment for low back disorders, but its
      benefit when compared with other exercise is less clear.

PMID- 28498225
TI  - Rehabilitation and Prevention of Proximal Hamstring Tendinopathy.
AB  - Proximal hamstring tendinopathy (PHT) comprises a small but significant portion
      of hamstring injuries in athletes, especially runners. PHT is a chronic condition
      that is clinically diagnosed but can be supported with imaging. The main
      presenting complaint is pain in the lower gluteal or ischial region that may or
      may not radiate along the hamstrings in the posterior thigh. There is little
      scientific evidence on which to base the rehabilitation management of PHT.
      Treatment is almost always conservative, with a focus on activity modification,
      addressing contributing biomechanical deficiencies, effective tendon loading
      including eccentric training, and ultrasound-guided interventional procedures
      which may facilitate rehabilitation. Surgery is limited to recalcitrant cases or
      those involving concomitant high-grade musculotendinous pathology. The keys to
      PHT management include early and accurate diagnosis, optimal rehabilitation to
      allow for a safe return to preinjury activity level, and preventative strategies
      to reduce risk of reinjury.

PMID- 28498226
TI  - Anterior Cruciate Ligament Injury: Return to Play, Function and Long-Term
      Considerations.
AB  - Anterior cruciate ligament tears are common and affect young individuals who
      participate in jumping and pivoting sports. After injury many individuals undergo
      ligament reconstruction (ACLR) but do not return to play, suffer recurrent injury
      and osteoarthritis. Outcome studies show that after ACLR, 81% of individuals
      return to sports, 65% return to their preinjury level and 55% return to
      competitive sports. Systematic reviews place the risk of ipsilateral retears at
      5.8% and contralateral injuries at 11.8%, with recent reports of over 20% failure
      rate. Approximately 20% to 50% of patients will have evidence of OA within 10 to
      20 yr. Factors important in reducing complications include timing of surgery,
      individualized return to play protocols, and prevention programs for injury.
      Further understanding of the factors that increase return to play percentages,
      reduce the risk of recurrent injury and improve long-term outcomes after ACL
      injury is needed to reduce the burden of these injuries on society.

PMID- 28498227
TI  - Mechanisms and Treatments for Shoulder Injuries in Overhead Throwing Athletes.
AB  - Shoulder injuries in overhead throwing athletes are very common. Throwing volume
      and mechanical forces that are placed on the glenohumeral joint and associated
      soft tissue structures are contributors. Poor biomechanics and weak links in the
      kinetic chain place this athletic population at increased risk for shoulder
      injuries. Common biomechanical deficiencies in overhead throwing athletes
      typically involve poor sequential timing of muscle activity and insufficient
      coordination also presented in shoulder elevation and other functional tasks.
      Kinetic chain deficits will lead to injury due to poor transference of energy
      from the lower extremities to the dominant upper extremity. Correction of these
      deficits involves effective treatment and prevention strategies. These include
      core and hip strengthening, balance training, optimize timing of biomechanical
      phases and events for each throwing movement, and following recommended rest
      guidelines. This article will synopsize current evidence of sport-specific injury
      mechanisms, injury treatment, and prevention of the shoulder in overhead throwing
      athletes.

PMID- 28498228
TI  - Psychological Issues Related to Illness and Injury in Athletes and the Team
      Physician: a Consensus Statement-2016 Update.

PMID- 28498229
TI  - Not Missing the Future: A Call to Action for Investigating the Role of
      Regenerative Medicine Therapies in Pediatric/Adolescent Sports Injuries.
AB  - In August 2016, a group including sport medicine clinicians, researchers, and a
      bioethicist met in Vail, Colorado to discuss regenerative medicine and its
      potential role in youth sports injuries. There was consensus that a call to
      action is urgently needed to understand the current evidence base, the risks and
      rewards, and future directions of research and clinical practice for regenerative
      medicine therapies in youth sports. We present here a summary of our meeting,
      which was supported by the National Youth Sports Health and Safety Institute
      (NYSHSI), a partnership between the American College of Sports Medicine (ACSM)
      and Sanford Health. The group's goal is to educate practitioners and the public,
      and to pioneer a means of accumulating meaningful clinical data on regenerative
      medicine therapies in pediatric and adolescent athletes.

PMID- 28498230
TI  - High Frequency of Neuroimaging Abnormalities Among Pediatric Patients With Sepsis
      Who Undergo Neuroimaging.
AB  - OBJECTIVES: This study was intended to describe and correlate the neuroimaging
      findings in pediatric patients after sepsis. DESIGN: Retrospective chart review.
      SETTING: Single tertiary care PICU. PATIENTS: Patients admitted to Cincinnati
      Children's Hospital Medical Center with a discharge diagnosis of sepsis or septic
      shock between 2004 and 2013 were crossmatched with patients who underwent
      neuroimaging during the same time period. INTERVENTIONS: All neuroimaging studies
      that occurred during or subsequent to a septic event were reviewed, and all new
      imaging findings were recorded and classified. As many patients experienced
      multiple septic events and/or had multiple neuroimaging studies after sepsis, our
      statistical analysis utilized the most recent or "final" imaging study available
      for each patient so that only brain imaging findings that persisted were
      included. MEASUREMENTS AND MAIN RESULTS: A total of 389 children with sepsis and
      1,705 concurrent or subsequent neuroimaging studies were included in the study.
      Median age at first septic event was 3.4 years (interquartile range, 0.7-11.5).
      Median time from first sepsis event to final neuroimaging was 157 days
      (interquartile range, 10-1,054). The most common indications for final imaging
      were follow-up (21%), altered mental status (18%), and fever/concern for
      infection (15%). Sixty-three percentage (n = 243) of final imaging studies
      demonstrated abnormal findings, the most common of which were volume loss (39%)
      and MRI signal and/or CT attenuation abnormalities (21%). On multivariable
      logistic regression, highest Pediatric Risk of Mortality score and presence of
      oncologic diagnosis/organ transplantation were independently associated with any
      abnormal final neuroimaging study findings (odds ratio, 1.032; p = 0.048 and odds
      ratio, 1.632; p = 0.041), although early timing of neuroimaging demonstrated a
      negative association (odds ratio, 0.606; p = 0.039). The most common abnormal
      finding of volume loss was independently associated with highest Pediatric Risk
      of Mortality score (odds ratio, 1.037; p = 0.016) and oncologic diagnosis/organ
      transplantation (odds ratio, 2.207; p = 0.001) and was negatively associated with
      early timing of neuroimaging (odds ratio, 0.575; p = 0.037). CONCLUSIONS: The
      majority of pediatric patients with sepsis and concurrent or subsequent
      neuroimaging have abnormal neuroimaging findings. The implications of this high
      incidence for long-term neurologic outcomes and follow-up require further
      exploration.

PMID- 28498231
TI  - Metrics to Assess Extracorporeal Membrane Oxygenation Utilization in Pediatric
      Cardiac Surgery Programs.
AB  - OBJECTIVES: Only a small fraction of pediatric cardiac surgical patients are
      supported with extracorporeal membrane oxygenation following cardiac surgery, but
      extracorporeal membrane oxygenation use is more common among those undergoing
      higher complexity surgery. We evaluated extracorporeal membrane oxygenation
      metrics indexed to annual cardiac surgical volume to better understand
      extracorporeal membrane oxygenation use among U.S. cardiac surgical programs.
      DESIGN: Retrospective analysis SETTING:: Forty-three U.S. Children's Hospitals in
      the Pediatric Health Information System that performed cardiac surgery and used
      extracorporeal membrane oxygenation. PATIENTS: All patients (< 19 yr) undergoing
      cardiac surgery during January 2003 to July 2014. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Both extracorporeal membrane oxygenation use and
      surgical mortality were risk adjusted using Risk Adjustment for Congenital Heart
      Surgery 1. Extracorporeal membrane oxygenation metrics indexed to annual cardiac
      surgery cases were calculated for each hospital and the metric values divided
      into quintiles for comparison across hospitals. Among 131,786 cardiac surgical
      patients, 3,782 (2.9%) received extracorporeal membrane oxygenation. Median case
      mix adjusted rate of extracorporeal membrane oxygenation use was 2.8%
      (interquartile range, 1.6-3.4%). Median pediatric cardiac case mix adjusted
      surgical mortality was 3.5%. Extracorporeal membrane oxygenation-associated
      surgical mortality was 1.3% (interquartile range, 0.7-1.6%); without
      extracorporeal membrane oxygenation, median case mix adjusted surgical mortality
      would increase from 3.5% to 5.0%. Among patients who died, 36.7% (median) were
      supported with extracorporeal membrane oxygenation. The median reduction in case
      mix adjusted surgical mortality from extracorporeal membrane oxygenation surgical
      survival was 30.1%. The median extracorporeal membrane oxygenation free surgical
      survival was 95% (interquartile range, 94-96%). Centers with less than 150 annual
      surgical cases had significantly lower median extracorporeal membrane oxygenation
      use (0.78%) than centers with greater than 275 cases (>= 2.8% extracorporeal
      membrane oxygenation use). Extracorporeal membrane oxygenation use and mortality
      varied within quintiles and across quintiles of center annual surgical case
      volume. CONCLUSIONS: Risk adjusted extracorporeal membrane oxygenation metrics
      indexed to annual surgical volume provide potential for benchmarking as well as a
      greater understanding of extracorporeal membrane oxygenation utilization,
      efficacy, and impact on cardiac surgery mortality.

PMID- 28498232
TI  - Antihypertensive Drugs Aliskiren, Nebivolol, and Olmesartan Reduce Hypertension
      by Reducing Endothelial Microparticles and Regulating Angiogenesis.
AB  - The accelerated generation of endothelial microparticles (EMPs) and impaired
      angiogenesis are the markers of vascular pathology during various cardiovascular
      and inflammatory conditions including hypertension. Because studies comparing the
      effects of antihypertensive agents on these 2 parameters are limited, this study
      was designed to compare the effects of 3 antihypertensive agents: aliskiren,
      nebivolol, and olmesartan, on the EMP generation and angiogenesis. Changes in the
      hemodynamic parameters and serum EMP count were determined after 3 weeks of the
      drug treatments [aliskiren (30 mg/kg), nebivolol (10 mg/kg), or olmesartan (5
      mg/kg) per orally] in L-NAME-induced rat model of hypertension. The 3 drugs
      prevented the rise in blood pressure and EMP count to a similar extent.
      Furthermore, nebivolol was found to possess more potent and concentration
      dependent antiangiogenic activity compared with aliskiren, whereas olmesartan was
      devoid of such an effect. The EMPs generated by virtue of the respective drug
      treatments were found to be involved in mediating the antiangiogenic effect of
      nebivolol and aliskiren. In addition, olmesartan treatment also resulted in the
      increased eNOS expression. The results of this study show that the
      antihypertensive drugs, viz. aliskiren, nebivolol, and olmesartan, regulate the
      vascular health by their differential effects on the EMP generation and
      angiogenesis.

PMID- 28498233
TI  - Wearable Sensor Technology Efficacy in Peripheral Vascular Disease (wSTEP): A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate the effect of using wearable activity monitors (WAMs) in
      patients with intermittent claudication (IC) within a single-center randomized
      controlled trial. BACKGROUND: WAMs allow users to set daily activity targets and
      monitor their progress. They may offer an alternative treatment to supervised
      exercise programs (SEPs) for patients with IC. METHODS: Thirty-seven patients
      with IC were recruited and randomized into intervention or control group. The
      intervention consisted of a feedback-enabled, wrist-worn activity monitor (WAM)
      in addition to access to SEP. The control group was given access to SEP only. The
      outcome measures were maximum walking distance (MWD), claudication distance (CD),
      and quality of life as measured by the VascuQol questionnaire. Participants were
      assessed upon recruitment, and at 3, 6, and 12 months. RESULTS: Patients in the
      WAM group showed significant improvement in MWD at 3 and 6 months (80-112 m, to
      178 m; P < 0.001), which was sustained at 12 months. The WAM group also increased
      CD (40 vs 110 m; P < 0.001) and VascuQol score (4.7 vs 5.8; P = 0.004). The
      control group saw a temporary increase in VascuQol score at 6 months (4.5 vs 4.7;
      P = 0.028), but no other improvements in MWD or CD were observed. Significantly
      higher improvements in MWD were seen in the WAM group compared with that in the
      control group at 6 months (82 vs -5 m; P = 0.009, r = 0.47) and 12 months (69 vs
      7.5 m; P = 0.011, r = 0.52). CONCLUSIONS: The study demonstrates the significant,
      sustained benefit of WAM-led technologies for patients with IC. This potentially
      resource-sparing intervention is likely to provide a valuable adjunct or
      alternative to SEP.

PMID- 28498234
TI  - Long-term Outcomes of Carotid Endarterectomy Versus Stenting in a Multicenter
      Population-based Canadian Study.
AB  - OBJECTIVE: To compare the long-term outcomes of patients treated with carotid
      endarterectomy and carotid-artery stenting. BACKGROUND: Evidence for the long
      term safety and efficacy of carotid-artery stenting compared with endarterectomy
      is accumulating from randomized trials. However, comparative data on the long
      term outcomes of carotid revascularization strategies in real world practice are
      lacking. METHODS: We conducted a population-based, multicenter, observational
      cohort study using validated linked databases from Ontario, Canada. We identified
      all individuals treated with carotid endarterectomy and stenting (2002-2014), and
      followed them up to 2015. We compared long-term (up to 13 years) and 30-day
      outcomes of each strategy using multilevel multivariable Cox proportional-hazards
      models, and conducted confirmatory analyses using propensity-score matching
      methods. RESULTS: In all, 15,525 patients received carotid-artery
      revascularization. Rate of the primary composite outcome of 30-day death, stroke,
      or myocardial infarction plus any stroke during 13-year follow-up was higher with
      stenting (16.3%) compared with endarterectomy (9.7%) [adjusted hazard ratio (HR)
      1.57, 95% confidence interval (CI) 1.43-1.73, P < 0.001). The increased risk with
      stenting was observed regardless of age, sex, intervention year, carotid-artery
      symptoms, or diabetes. The primary outcome was driven by higher rates of 30-day
      stroke (adjusted HR 1.59, 95% CI 1.29-1.95), 30-day death (adjusted HR 2.62, 95%
      CI 2.20-3.13), and long-term stroke >30 days after the procedure (adjusted HR
      1.47, 95% CI 1.36-1.59) with stenting; 30-day myocardial infarction was lower
      with stenting (adjusted HR 0.70, 95% CI 0.57-0.86). These results were confirmed
      with 1:2 propensity-score matching (HR for primary composite outcome with
      stenting 1.55, 95% CI 1.31-1.83, P < 0.001). CONCLUSIONS: Compared with carotid
      endarterectomy, stenting was associated with an early and sustained approximately
      55% increased hazard for major adverse events over long-term follow-up. Although
      nonrandomized, these results raise potential concerns about the
      interchangeability of carotid endarterectomy and stenting in the context of
      actual clinical practice.

PMID- 28498235
TI  - Hospital Minimally Invasive Surgery Utilization for Gastrointestinal Cancer.
AB  - OBJECTIVE: The aim of the study was to evaluate the impact of receiving care at
      high minimally invasive surgery (MIS)-utilizing hospitals BACKGROUND:: MIS
      techniques are used across surgical specialties. The extent of MIS utilization
      for gastrointestinal (GI) cancer resection and impact of receiving care at high
      utilizing hospitals is unclear. METHODS: This is a retrospective cohort study of
      137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary,
      colon, and rectal cancer patients within the National Cancer Data Base (2010
      2013). Disease-specific, hospital-level, reliability-adjusted MIS utilization
      rates were calculated to evaluate perioperative outcomes. Among patients for whom
      adjuvant chemotherapy (AC) was indicated, the association between days to AC and
      hospital MIS utilization was examined using generalized estimating equations.
      Association with risk of death was evaluated using multivariable Cox regression.
      RESULTS: Disease-specific MIS use increased significantly [42.0%-68.3% increase;
      trend test, P < 0.001 for all except hepatobiliary (P = 0.007)] over time. Most
      hospitals [range-30.3% (colon); 92.9% (pancreatic)] were low utilizers (<=30% of
      cases). Higher MIS utilization is associated with increased lymph nodes examined
      (P < 0.001, all) and shorter length of stay (P < 0.001, all). Each 10% increase
      in MIS utilization is associated with fewer days to AC [3.3 (95% confidence
      interval, 1.2-5.3) for MIS gastric; 3.3 ([0.7-5.8) for open gastric; 1.1 (0.3
      2.0) days for open colon]. An association between MIS utilization and risk of
      death was observed for colon [Q2-hazard ratio (HR) 0.96 (0.89-1.02); Q3-HR 0.91
      (0.86-0.98); Q4-HR 0.87 (0.82-0.93)] and rectal cancer [Q2-HR 0.89 (0.76-1.05);
      Q3-HR 0.84 (0.82-0.97); Q4-HR 0.86 (0.74-0.98)]. CONCLUSIONS: Most hospitals
      treating GI malignancies are low MIS utilizers. Our findings may reflect real
      world MIS effectiveness for oncologic resection and could be useful for
      identifying hospitals with infrastructure and/or processes beneficial for
      multimodality cancer care.

PMID- 28498236
TI  - Feasibility of Transabdominal Cardiophrenic Lymphnode Dissection in Advanced
      Ovarian Cancer: Initial Experience at a Tertiary Center.
AB  - OBJECTIVES: The purpose of this retrospective report is to define the safety and
      feasibility, based on our preliminary experience, of surgical transdiaphragmatic
      resection of enlarged cardiophrenic lymph nodes (CPLNs), as a part of upfront
      debulking surgery. Supradiaphragmatic nodes located between the diaphragm and the
      heart are frequently a location for lymph node metastasis in advanced ovarian
      cancer, and their removal is aimed to obtain no gross residual disease at the
      primary cytoreductive surgery often requiring aggressive surgical procedures.
      PATIENTS AND METHODS: Between May 2012 and October 2016, a total of 22 patients
      among 443 with advanced high-grade serous ovarian cancer underwent cytoreductive
      procedures involving transdiaphragmatic resection of enlarged CPLNs at European
      Institute of Oncology in Milan. RESULTS: All patients who underwent CPLN
      resection had an extensive disease (median peritoneal cancer index, 18), and more
      than 77% required complex surgical procedures (complexity score, 3). No residual
      abdominal disease less than 5 mm at the end of surgery was described in 20 (90%)
      out of 22. All patients but one had confirmed CPLN positive nodes at
      histopathological study. The average operative time was 333 min (range, 244-455
      min), and the average estimated blood loss was 1000 mL (range, 400-2000 mL).
      Blood transfusion was necessary in 13 out of 22 patients. Only 7 (33%) out of 21
      patients required chest tube placement during the postoperative period.
      CONCLUSIONS: Transdiaphragmatic enlarged CPLN resection seems to be safe and
      feasible procedure when indicated to achieve no or minimal tumor residual
      disease. Nevertheless, its impact on survival of patients with stage IV ovarian
      cancer needs to be determined.

PMID- 28498237
TI  - Enhanced Recovery After Surgery for Advanced Ovarian Cancer: A Systematic Review
      of Interventions Trialed.
AB  - OBJECTIVES: We sought to summarize the evidence for interventions aiming at
      enhanced recovery after surgery (ERAS) in ovarian cancer through a systematic
      review. METHODS: We searched MEDLINE, EMBASE, and The Cochrane Library for
      studies testing ERAS interventions in patients undergoing surgery for ovarian
      cancer. Study selection and data extraction were done independently by 2
      reviewers with disagreements resolved by discussion with a senior, third
      reviewer. RESULTS: We identified 25 studies including 1648 participants with
      ovarian cancer. Nine observational studies addressed ERAS protocols. Four of them
      were prospective, and 3 included historical controls. The other 16 studies
      reported single interventions, for example, early feeding, omission of pelvic
      drains, early orogastric tube removal, Doppler-guided fluid management, and
      patient-controlled epidural analgesia. Early feeding protocols were tested in 7
      of the 12 randomized trials. Early feeding appeared to be safe and was associated
      with significantly faster recovery of bowel function. CONCLUSIONS: Few studies
      have specifically studied ERAS interventions in ovarian cancer. All studies on
      protocols including multiple interventions were susceptible to bias. Early
      feeding is the intervention that is best supported by randomized trials.
      Application of evidence for ERAS derived from nonovarian cancer is challenged by
      the differences not only in the scope of surgery but also in ovarian cancer
      patients' comorbidities. Postoperative morbidity is particularly high in these
      patients because of their poor nutritional status, perioperative fluids shifts,
      and long operating times. These patients may also show excessive response to
      surgical stress. Innovative, randomized trials are needed to reliably determine
      the feasibility, safety, and effectiveness of specific ERAS interventions in
      ovarian cancer.

PMID- 28498238
TI  - Nomogram Predicting Overall Survival in Operable Cervical Cancer Patients.
AB  - OBJECTIVE: Nomograms are widely used as predictive tools to predict oncological
      outcomes intuitively and precisely. The aim of our study was to develop a
      nomogram for predicting overall survival (OS) of patients with early stage
      cervical cancer. METHODS: In this retrospective study, the clinical,
      pathological, and hematological data and prognosis of 795 cervical cancer
      patients were investigated. We identified and incorporated independent
      significant prognostic factors for OS to develop a nomogram. The predictive
      accuracy and discriminative ability were measured by concordance index. RESULTS:
      By univariable analysis and subsequent multivariable analysis, we identified body
      mass index, albumin, platelet, leukocyte, tumor differentiation, and the status
      of the pelvic lymph node (PLN) (all P < 0.05) as independent prognostic factors.
      The concordance index of the nomogram integrating these 6 variables was 0.74. The
      calibration curves for probability of 3- and 5-year OS also demonstrated ideal
      agreement between nomogram prediction and actual observation. CONCLUSIONS: We
      developed a novel nomogram that can provide prediction of OS for patients with
      early stage cervical cancer individually. Furthermore, studies are required to
      validate whether it can be applied to other cohorts.

PMID- 28498239
TI  - The Validity of Using Human Squamous Cell Carcinoma Associated Antigen and
      Cytokeratin 19 Fragment Antigen 21-1 to Predict Postoperative Adjuvant
      Radiotherapy for Nonbulky Early-Stage Squamous Cell Carcinoma of the Cervix.
AB  - OBJECTIVE: There are no generally accepted biomarkers for the optimal selection
      of radiotherapy-based or surgical-based treatment options for nonbulky early
      stage squamous cell carcinoma of the cervix (IA1-IB1 and IIA1). The objective of
      this study was to assess the value of human squamous cell carcinoma-associated
      antigen (SCC-Ag) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in
      evaluation of patients with nonbulky early-stage squamous cell carcinoma of the
      cervix to determine if radiotherapy is warranted after radical surgery. METHODS:
      Patients with stage IA1-IB1 and IIA1 squamous cell carcinoma of the cervix who
      were treated at the Department of Gynecological Oncology, Affiliated Tumor
      Hospital of Guangxi Medical University, from March 2012 to August 2014 (n = 308)
      were treated with radical hysterectomy and pelvic lymphadenectomy. The levels of
      SCC-Ag and CYFRA21-1 were detected by enzyme-linked immunosorbent assay before
      surgery. The relationship between the concentrations of SCC-Ag and CYFRA21-1 and
      risk factors was estimated through logistic regression and analysis of variance t
      test. The cutoff values of these 2 markers to evaluate the need for postoperative
      radiotherapy were identified and validated by receiver operating characteristic
      curve and kappa consistency test, respectively. RESULTS: Serum SCC-Ag and CYFRA21
      1 levels are significantly increased in patients who require postoperative
      radiotherapy with a risk factor score of at least 2 (n = 162). Logistic
      regression analysis revealed that deep stromal invasion and lymph node metastasis
      are independent risk factors for serum SCC-Ag value, and deep stromal invasion is
      an independent risk factor for the serum CYFRA21-1 value. Receiver operating
      characteristic curve revealed that the best predictive cutoff points of SCC-Ag
      and CYFRA21-1 values were 1.425 and 3.210 ng/mL, respectively. These results were
      validated by the kappa consistency test applied to a validation group of
      patients. The results suggest that most patients with SCC-Ag and CYFRA21-1 values
      of at least 1.425 and 3.210 ng/mL, respectively, require postoperative
      radiotherapy. CONCLUSIONS: Detection of the levels of SCC-Ag and CYFRA21-1 may
      help guide an individual primary treatment plan for patients with nonbulky early
      stage squamous cell carcinoma of the cervix.

PMID- 28498240
TI  - Simple Vaginal Trachelectomy: A Valuable Fertility-Preserving Option in Early
      Stage Cervical Cancer.
AB  - OBJECTIVE: Radical trachelectomy is a valid alternative for the treatment of
      early-stage cervical cancer in young women who wish to preserve fertility
      potential. Recent data indicate that even less radical surgery could be performed
      in low-risk cases. The objective of our study was to evaluate the safety of
      simple vaginal trachelectomy and node assessment in patients with low-risk, early
      stage cervical cancer (<2 cm). METHODS: From May 2007 to July 2016, 35 women
      underwent a simple vaginal trachelectomy with laparoscopic sentinel lymph node
      mapping + pelvic node dissection. Data were collected prospectively in a
      computerized database. Descriptive statistics and Kaplan-Meier estimate were used
      for analysis. RESULTS: Patients' median age was 29 years, and 24 (69%) were
      nulliparous. Eight had stage IA1 with lymphovascular space invasion, 9 a stage
      IA2, and 18 a stage IB1. Nineteen (54%) had squamous histology, 13 (37%) had
      adenocarcinoma, and 3 had other histologic findings. The median operating room
      time was 148 minutes (90-240 minutes), and median blood loss was 50 mL (25-200
      mL). On final pathology, lymph nodes were negative in all patients, except 2
      cases with isolated tumor cells. Twenty-two patients (63%) had either no residual
      disease in the trachelectomy specimen (n = 15) or residual dysplasia only (n =
      7). With a median follow-up of 42 months (1-100 months), 1 local recurrence
      occurred treated initially with chemoradiation and then a pelvic exenteration.
      The recurrence-free survival at 48 months is 96.7%. There were 25 pregnancies: 5
      (20%) ended in the first trimester, 2 delivered prematurely at 34.4 and at 35
      weeks, and all the others (18 [72%]) delivered at more than 36 weeks.
      CONCLUSIONS: Based on our experience, simple trachelectomy and nodes appear to be
      a safe fertility-preserving surgery in well-selected patients with small-volume
      cervical cancer. Obstetric outcome appears favorable.

PMID- 28498241
TI  - Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational
      Trophoblastic Neoplasia.
AB  - OBJECTIVE: The aim of this study was to develop a serum human chorionic
      gonadotropin (hCG) normogram for both uneventful complete and partial
      hydatidiform moles in the first-trimester ultrasound era. METHODS: An hCG
      normogram for both complete and partial hydatidiform moles was constructed, based
      on 639 patients with uneventful serum hCG regression after evacuation between
      1990 and 2014. Serum hCG was measured by an in-house-developed radioimmunoassay,
      detecting both intact hCG and free beta-subunit. It has been in use for all serum
      measurements sent to the Dutch Central Registry for Hydatidiform Moles since
      1977. RESULTS: Since introduction of routine first-trimester ultrasonography,
      lower pre-evacuation and follow-up serum hCG concentrations were observed. When
      compared with complete hydatidiform moles, patients with a partial hydatidiform
      mole had significantly lower pre-evacuation serum hCG concentration (median, 4400
      and 875 ng/mL, respectively; P < 0.001) and earlier hCG normalization (median, 7
      and 6 weeks, respectively; P < 0.001) but higher gestational age (mean, 11.5 and
      13.0 weeks, respectively; P < 0.001). For both complete and partial hydatidiform
      moles, 95% of patients reached normal serum hCG concentrations within 14 weeks
      after evacuation. CONCLUSIONS: A normogram for the detection of gestational
      trophoblastic neoplasia was developed for complete and partial hydatidiform
      moles. Although interesting from a scientific perspective, the small divergence
      in hCG regression between complete and partial hydatidiform moles will be of
      little importance in clinical practice, as actual differences in regression will
      encompass only days. To promote clarity and unity in daily practice, we therefore
      propose a combined normogram to be used as a reference guideline for follow-up
      after evacuation of a hydatidiform mole. This normogram will be compliant with
      patients in today's clinical practice.

PMID- 28498242
TI  - Rivaroxaban Used in the Treatment Patients With Gynecologic Cancer and Venous
      Thromboembolism: The Experience of Instituto Nacional de Cancer-Rio de Janeiro,
      Brazil.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is a major complication of malignant
      diseases and is a frequent cause of death in patients with cancer. Managing
      anticoagulation in these patients is challenging because of the high risk of
      recurrent VTE and bleeding events. Rivaroxaban is an oral anticoagulant that
      provides rapid onset of anticoagulation. OBJECTIVE: The aim of this study was to
      describe the complications of rivaroxaban and potentially associated factors in
      patients with gynecologic cancer and VTE. METHODS: This was an observational
      study in women with gynecological cancer who developed VTE and were treated with
      15 and 20 mg rivaroxaban at Instituto Nacional de Cancer from July 2014 to July
      2015. RESULTS: Forty-one patients were treated with rivaroxaban. Most patients
      were younger than 60 years and presented cervical cancer; 58.5% of women did not
      have complications, thus remaining at a dose of 20 mg/d. Because of
      complications, 12.2% had the dose reduced to 15 mg/d, 12.2% had the drug
      suspended, 7.3% had progressive worsening of the disease with suspension of
      anticoagulation, and 9.8% progressed to death because of progression of the
      disease. CONCLUSIONS: Rivaroxaban has been documented as a low-cost, easily
      controlled option compared with standard therapy. Most participants in this study
      had no complications. However, it was not possible to assess associations with
      statistical significance. Further analytical studies with larger samples are
      required to evaluate the safety and efficacy of this treatment in patients with
      gynecologic cancer.

PMID- 28498243
TI  - A Controlled Study on Vaginal Blood Flow During Sexual Arousal Among Early-Stage
      Cervical Cancer Survivors Treated With Conventional Radical or Nerve-Sparing
      Surgery With or Without Radiotherapy.
AB  - OBJECTIVE: Sexual problems among cervical cancer survivors may in part be caused
      by reduced vaginal blood flow due to damaged hypogastric nerves during radical
      hysterectomy with pelvic lymphadenectomy and/or by radiation-induced vaginal
      changes after pelvic radiotherapy. A nerve-sparing modification of radical
      hysterectomy (NSRH) may preserve vaginal blood flow. Vaginal blood flow during
      sexual arousal was compared between different treatment modalities. METHODS: We
      investigated premenopausal women treated for early-stage cervical cancer with
      radical hysterectomy (n = 29), NSRH (n = 28), NSRH with radiotherapy (n = 14),
      and controls (n = 31). Genital arousal and subjective sexual arousal in response
      to sexual stimuli were measured using vaginal photoplethysmography and a
      questionnaire. Results were compared by using a between-study (treatment groups)
      by within-study (stimulus) design. RESULTS: Participants were aged 29 to 51 years
      (mean, 42 years) and at 1 to 14 years (mean, 5 years) after treatment. Measured
      vaginal blood flow in women treated with NSRH was similar to controls. Women
      treated with radical hysterectomy had a significantly lower vaginal blood flow
      compared with controls overall and lower compared with the NSRH group during
      sexual stimulation. Women treated with radiotherapy had a vaginal blood flow
      intermediate between the other groups without significant differences. The erotic
      films were equally effective in enhancing subjective sexual arousal among
      treatment groups. CONCLUSIONS: Cervical cancer treatment with radical
      hysterectomy disrupts the vaginal blood flow response, and this may be prevented
      by conducting an NSRH. Treatment with radiotherapy did not significantly impact
      vaginal blood flow, but further investigation is needed with a larger sample.

PMID- 28498244
TI  - Identifying Lynch Syndrome in Women Presenting With Endometrial Carcinoma Under
      the Age of 50 Years.
AB  - BACKGROUND: Lynch syndrome (LS) is an inherited disorder associated with genetic
      predisposition to endometrial, colorectal, ovarian, and other cancers. There is
      consensus for the necessity of assessment for LS in view of the established
      survival benefits for identified patients and affected family members. The debate
      regarding the best screening policy is far from being concluded. OBJECTIVES: The
      aim of this study was to evaluate a realistic protocol for identifying LS
      families by assessing young women with a diagnosis of endometrial cancer (EC).
      METHODS: Consecutive cases of women with a diagnosis of endometrioid EC younger
      than 50 years were recruited. A complete 3-generation pedigree was drawn and
      assessed against the Amsterdam II criteria. Tumor DNA microsatellite instability
      and immunohistochemistry testing for the expression of mismatch repair (MMR)
      proteins MLH1, MSH2, MSH6, and PMS2 was offered to all patients. MLH1 gene
      promoter methylation and EPCAM gene deletion testing were also offered where
      appropriate. Genetic counseling and MMR germline mutation tests were offered in
      women with abnormal results. RESULTS: Fifty-eight women were invited, and 38
      (65.5%), consented for LS assessment (95% confidence interval CI 53%-78%). A
      complete data set was obtained in 35 women (60.3%). Lynch syndrome according to
      clinical and/or molecular characteristics was diagnosed in 8 cases or 22.8% (95%
      CI 15%-48%). There was no significant difference at the age of women with a
      diagnosis of LS (median, 45 years; range, 37-48 years) compared with that of the
      non-LS ones (median, 45 years; range, 31-49 years). Three pathogenic MMR
      mutations were identified in the 8 cases with a diagnosis of LS, 37.5% (95% CI 5%
      72%), estimating an 8.5% (95% CI 1%-19%) mutation prevalence in the study
      population. CONCLUSIONS: All women with newly diagnosed EC should be assessed for
      inherited predisposition. Regional policies for assessment should be developed in
      accordance with available resources. Gynecologists are required to upgrade their
      skills in order to identify, assess, and counsel patients with suspected or
      established LS and appropriately refer to clinical genetics.

PMID- 28498245
TI  - Increased Endothelial Progenitor Cell Number in Early Stage of Endometrial
      Cancer.
AB  - OBJECTIVES: It is generally believed that circulating endothelial cells (CECs)
      and endothelial progenitor cells (EPCs) reflect the state of the endothelium, its
      injury and/or repair possibilities. In different types of cancers, increased
      numbers of CECs and EPCs were found, suggesting their participation in cancer
      angiogenesis. The objective of this study was to determine whether, in the blood
      circulation of women with early endometrial cancer, CEC and EPC levels differ
      from those of healthy women of similar age. METHODS: For CEC number evaluation,
      samples of peripheral blood cells of women with endometrial carcinoma and control
      subjects were labeled with anti-CD31 and anti-CD45 antibodies; for EPCs, with
      anti-VEGFR2 (vascular-endothelium growth factor receptor 2)/KDR and anti-CD34
      antibodies. The CEC and EPC cells were then quantified by flow cytometry.
      RESULTS: Endothelial progenitor cell numbers (CD34, VEGFR2/KDR) in the peripheral
      blood of women with endometrial carcinoma were significantly augmented as
      compared with those of control healthy women and CEC numbers (CD31, CD45) were
      similar in both groups. Cancer patients were divided according to the grading
      into G1 and G2 groups and according to the stage into International Federation of
      Gynecology and Obstetrics (FIGO) stage IA and FIGO IB groups. Statistically
      significant augmented EPC numbers were demonstrated only in G1 and FIGO IA
      patients. CONCLUSIONS: These results strongly suggest new vessel formation from
      recruited endothelial precursors as being involved mainly at the early stages of
      tumor progression.

PMID- 28498247
TI  - Practice Patterns of Hereditary Ovarian Cancer Management in Korea.
AB  - OBJECTIVE: This study aims to evaluate practice patterns for managing hereditary
      ovarian cancer among Korean gynecologic oncologic physicians. METHODS: Members of
      the Korean Society of Gynecologic Oncology participated in the inaugural
      Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail
      from January to February 2016. The survey was conducted using a self-administered
      questionnaire. RESULTS: Most physicians (66.7%, 36/54) responded to draw a
      pedigree of patients with a family history. The rate of genetic test
      recommendations for patients at risk for ovarian cancer was high (96.3%, 52/54).
      Physicians tended to select appropriate candidates for the genetic test. Of the
      respondents, genetic counseling was commonly performed before the genetic test
      (76.6%, 36/47) and provided by the specialist consultant(s) (78.7%, 37/47) or the
      physician alone (12.8%, 6/47). Participants showed mature response to risk
      management for the BRCA carriers: at least annual gynecologic surveillance
      (89.4%, 42/47), recommendation for chemoprevention (76.6%, 36/47), and advice for
      risk-reducing salpingo-oophorectomy (85.1%, 40/47). Risk-reducing salpingectomy
      with delayed oophorectomy as an alternative to risk-reducing salpingo
      oophorectomy was considered to recommend in most of respondents (91.5%, 43/47).
      CONCLUSIONS: Gynecologic oncologic physicians in Korea had high awareness to
      genetic risk assessment, candidate selection to genetic test, and risk-reducing
      strategies for the management of hereditary ovarian cancer.

PMID- 28498246
TI  - Endometrial Cancers With Activating KRas Mutations Have Activated Estrogen
      Signaling and Paradoxical Response to MEK Inhibition.
AB  - OBJECTIVES: The aims of this study were to determine if activating KRas mutation
      alters estrogen signaling in endometrial cancer (EC) and to explore the potential
      therapeutic impact of these alterations. METHODS: The Cancer Genome Atlas was
      queried for changes in estrogen-regulated genes in EC based on KRas mutation
      status. In vitro studies were conducted to evaluate estrogen receptor alpha
      (ERalpha) phosphorylation changes and related kinase changes in KRas mutant EC
      cells. The resulting effect on response to MEK inhibition, using trametinib, was
      evaluated. Immunohistochemistry was performed on KRas mutant and wild-type EC
      tumors to test estrogen signaling differences. RESULTS: KRas mutant tumors in The
      Cancer Genome Atlas showed decreased progesterone receptor expression (P =
      0.047). Protein analysis in KRas mutant EC cells also showed decreased expression
      of ERalpha (P < 0.001) and progesterone receptor (P = 0.001). Although total
      ERalpha is decreased in KRas mutant cells, phospho-ERalpha S118 was increased
      compared with wild type. Treatment with trametinib in KRas mutant cells increased
      phospho-ERalpha S167 and increased expression of estrogen-regulated genes. While
      MEK inhibition blocked estradiol-stimulated phosphorylation of ERK1/2 and p90RSK
      in wild-type cells, phospho-ERK1/2 and phospho-p90RSK were substantially
      increased in KRas mutants. KRas mutant EC tumor specimens showed similar changes,
      with increased phospho-ERalpha S118 and phospho-ERalpha S167 compared with wild
      type EC tumors. CONCLUSIONS: MEK inhibition in KRas mutant cells results in
      activation of ER signaling and prevents the abrogation of signaling through
      ERK1/2 and p90RSK that is achieved in KRas wild-type EC cells. Combination
      therapy with MEK inhibition plus antiestrogen therapy may be necessary to improve
      response rates in patients with KRas mutant EC.

PMID- 28498248
TI  - C1GALT1 Seems to Promote In Vitro Disease Progression in Ovarian Cancer.
AB  - OBJECTIVE: Aberrant glycosylation affects many cellular properties in cancers.
      The core 1 beta1,3-galactosyltransferase (C1GALT1), an enzyme that controls the
      formation of mucin-type O-glycans, has been reported to regulate hepatocellular
      and mammary carcinogenesis. This study aimed to explore the role of C1GALT1 in
      ovarian cancer. METHODS: C1GALT1 expression was assessed in a public database
      based on microarray data from 1287 ovarian cancer patients and ovarian cancerous
      tissues. Lectin blotting and flow cytometry analysis were conducted to detect
      changes in O-glycans on ovarian cancer cells. Effects of C1GALT1 on cell growth,
      migration, and sphere formation were analyzed in C1GALT1 knockdown or
      overexpressing ovarian cancer cells in vitro. Expression of cancer stemness
      related genes was analyzed by quantitative reverse transcription polymerase chain
      reaction. RESULTS: High C1GALT1 expression shows a trend toward association with
      poor survival in ovarian cancer patients. C1GALT1 modifies O-glycan expression on
      surfaces and glycoproteins of ovarian cancer cells. Knockdown of C1GALT1
      decreased cell growth, migration, and sphere formation of ES-2 and OVTW59-p4
      cells. Conversely, overexpression of C1GALT1 promoted such malignant properties
      of SKOV3 cells. Furthermore, C1GALT1 regulated the expression of several cancer
      stemness-related genes, including CD133, CD24, Oct4, Nanog, and SNAI2, in ovarian
      cancer cells. CONCLUSIONS: C1GALT1 modifies O-glycan expression and enhances
      malignant behaviors in ovarian cancer cells, suggesting that C1GALT1 plays a role
      in the pathogenesis of ovarian cancer and targeting C1GALT1 could be a promising
      approach for ovarian cancer therapy.

PMID- 28498249
TI  - Clinicopathological Characteristics and Prognostic Factors of Synchronous
      Endometrial and Ovarian Cancers-A Single-Institute Review of 43 Cases.
AB  - OBJECTIVES: The objectives of our study were to demonstrate the
      clinicopathological characteristics and determine the prognostic factors for
      women with synchronous primary cancers of the endometrium and ovary. METHODS: A
      retrospective analysis of 43 pathologically proven cases of synchronous primary
      endometrial and ovarian cancers diagnosed between January 2005 and December 2015
      was carried out. Patients with uterine sarcomas, carcinosarcomas, borderline
      tumors, and nonepithelial tumors of the ovary and patients who received
      neoadjuvant chemotherapy were excluded from the study. Disease-free survival
      (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier
      method. Multivariate analysis to determine independent prognostic factors was
      performed using the Cox regression model. RESULTS: Mean age at diagnosis was
      48.49 years. The most common presenting symptom was abnormal uterine bleeding in
      58.2% of the patients. Nineteen patients (44.2%) were obese, and 13 patients
      (30.2%) were overweight. Twelve patients (30%) were nulliparous, and 25 (58.2%)
      were premenopausal; 76.7% of the patients received adjuvant treatment after
      surgery. Mean follow-up period was 48.9 months. Twelve patients developed
      recurrence, and 7 patients died of recurrent disease. The 5-year DFS for all
      patients was 65.13%, and the 5-year OS was 79.75%. The 118-month DFS and 118
      month OS were 65.13% and 72.50%, respectively. On multivariate analysis, grade 3
      disease for both endometrial and ovarian cancers and presence of lymphovascular
      space invasion were associated with significantly worse 118-month DFS and OS,
      respectively. CONCLUSIONS: Women with synchronous primary endometrial and ovarian
      cancers are young, nulliparous, obese, and premenopausal and have a favorable
      overall prognosis. Grade 3 disease at both sites and presence of lymphovascular
      space invasion are independent prognostic factors for recurrence and survival,
      respectively.

PMID- 28498250
TI  - Prediction of Site-Specific Tumor Relapses in Patients With Stage I-II
      Endometrioid Endometrial Cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the association of predictors
      of an advanced disease and/or poor outcome with the occurrence of tumor relapses
      in different anatomical sites in patients with stage I-II endometrioid
      endometrial cancer. METHODS: A total of 929 patients were included in the study.
      The median follow-up time was 57 months (range, 1-108 months). The studied
      variables were: poor tumor differentiation, myometrial invasion 50% or greater,
      tumor size 3 cm or greater, lymphovascular space invasion, cervical stromal
      invasion, positive peritoneal cytology, old age (>77 years), obesity (body mass
      index >=30 kg/m), and diabetes. RESULTS: A relapse was diagnosed in 98 patients
      (10.5%) (vaginal in 15, pelvic in 27, intra-abdominal beyond the pelvis in 27,
      extra-abdominal in 29). None of the variables were associated with an altered
      risk of vaginal or pelvic relapses in univariate analyses. Poor differentiation,
      myometrial invasion 50% or greater, tumor size 3 cm or greater, and positive
      peritoneal cytology were associated with an increased risk of intra-abdominal
      relapses beyond the pelvis (odds ratios [ORs] between 2.2 and 9.6). With the
      exception of obesity and diabetes, all variables were associated with an
      increased risk of extra-abdominal relapses (ORs between 2.3 and 13). Tumor size 3
      cm or greater (OR, 3.1) and positive peritoneal cytology (OR, 16) predicted intra
      abdominal relapses beyond the pelvis in multivariate analysis, whereas poor
      differentiation (OR, 2.9), myometrial invasion 50% or greater (OR, 4.0), and
      positive peritoneal cytology (OR, 27) predicted extra-abdominal relapses.
      Compared with vaginal relapses, intra-abdominal relapses beyond the pelvis and
      extra-abdominal relapses were associated with a worse disease-specific survival.
      Survival of patients with a pelvic relapse did not differ from that of patients
      with a vaginal relapse. CONCLUSIONS: Risk variables of endometrial cancer are
      differently associated with relapses in different locations. Our findings may
      promote studies that explore the most efficient adjuvant therapy in high-risk
      early-stage endometrioid endometrial cancer.

PMID- 28498251
TI  - Undiagnosed Uterine Sarcomas Identified During Surgery for Presumed Leiomyoma at
      a National Tertiary Hospital in Thailand: A 10-Year Review.
AB  - OBJECTIVES: The aim of this study was to evaluate the rate, clinical
      characteristics, and survival outcomes of an undiagnosed uterine malignancy in
      patients who underwent surgical treatment for presumed leiomyomas. METHODS:
      Medical records of patients who underwent surgical treatment for presumed
      leiomyomas, from January 2004 to September 2013, were retrospectively reviewed,
      and the data were followed until September 2016. Demographic data, tumor
      characteristics, oncologic treatment, and response rate were analyzed by
      descriptive statistics. Kaplan-Meier method was used for survival analysis. This
      study includes follow-up data through December 31, 2016. RESULTS: A total of
      11,258 medical records of presumed leiomyoma patients undergoing hysterectomy
      during the studied period were reviewed. Pathology of uterine sarcoma was found
      in 22 patients (0.2%), all of whom were included. Nineteen patients had
      leiomyosarcoma, and 3 had endometrial stromal sarcoma. Mean age of patients was
      48.3 +/- 6.9 years. All patients underwent total abdominal hysterectomy, with 20
      patients undergoing concurrent bilateral salpingo-oophorectomy. Uterine sarcoma
      was classified as stage IB in 21 patients and stage IIIC in 1 patient. Fifteen
      patients were prescribed the following adjuvant treatment: chemotherapy in 13
      patients and megestrol acetate in 2 patients. Thirteen patients had recurrent
      disease, and 3 patients died of their disease. The mean progression-free survival
      was 50.1 +/- 41.3 months, and overall survival was 59.3 +/- 43.0 months.
      CONCLUSIONS: One in 512 patients who underwent hysterectomy because of presumed
      uterine leiomyomas had inadvertent uterine sarcomas. Even with adjuvant therapy,
      treatment outcome was rather poor, with almost 60% recurrence rate and median
      progression-free survival and overall survival of less than 5 years.

PMID- 28498252
TI  - Completing or Abandoning Radical Hysterectomy in Early-Stage Lymph Node-Positive
      Cervical Cancer: Impact on Disease-Free Survival and Treatment-Related Toxicity.
AB  - INTRODUCTION: Management regarding completing hysterectomy in case of
      intraoperative finding of positive lymph nodes in early-stage cervical cancer
      differs between institutions. The aim of this study was to compare survival and
      toxicity after completed hysterectomy followed by adjuvant (chemo-)radiotherapy
      versus abandoned hysterectomy and primary treatment with chemoradiotherapy (CRT).
      METHODS: A retrospective multicenter cohort study was performed. All patients
      were scheduled for radical hysterectomy with pelvic lymphadenectomy (RHL). In the
      RHL group, hysterectomy was completed followed by adjuvant (chemo-)radiotherapy.
      In the second group, hysterectomy was abandoned, and CRT was conducted. Primary
      outcomes were disease-free survival (DFS) and overall survival. A multivariable
      analysis on DFS was performed. Toxicity was scored according to the National
      Cancer Institute CTCAE (Common Terminology Criteria for Adverse Events) v4.03.
      RESULTS: A total of 121 patients were included (RHL, n = 89; CRT, n = 32). There
      was no difference in overall survival (84% vs 77%). Five-year DFS was in favor of
      completing RHL (81% vs 67%). Multivariable analysis showed that, corrected for
      lymph node variables, treatment regimen was not associated with DFS. After RHL,
      pelvic recurrence rate was significantly lower compared with CRT (2% vs 16%).
      CTCAE grade 3-4 toxicity rates were higher in the CRT compared with the RHL group
      (59% vs 30%), mainly because of differences in chemotherapy-related hematologic
      toxicity. CONCLUSIONS: In patients with clinically N0 early-stage cervical cancer
      with intraoperative detection of positive nodes, completing RHL followed by
      adjuvant (chemo-)radiotherapy may result in a better pelvic control compared with
      abandoning hysterectomy and treatment with chemoradiotherapy. However, if
      corrected for lymph node variables, treatment (RHL or CRT) was not associated
      with DFS.

PMID- 28498253
TI  - Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum
      Resistant Ovarian Cancer.
AB  - OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to
      uncontrolled cell proliferation and dysregulation of FOXM1 transcription network
      occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a
      thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if
      targeting the FOXM1 pathway with thiostrepton could improve the efficacy of
      paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS:
      Human ovarian cancer cell lines and patients' ascites cells were treated with
      paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and
      cytotoxicity was assessed. Drug combination effects were determined by
      calculating the combination index values using the Chou and Talalay method.
      Quantitative real-time polymerase chain reaction was performed to determine
      changes in FOXM1 expression and its downstream targets. RESULTS: Ovarian cancer
      cell lines and the patients' ascites cancer cells had an overexpression of FOXM1
      expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA
      expression and its downstream targets such as CCNB1, CDC25B, leading to cell
      death in both cell lines and patients' ascites cancer cells. Furthermore,
      addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects
      in chemoresistant ovarian cancer patients' ascites cells ex vivo. CONCLUSION:
      Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial
      ovarian cancer.

PMID- 28498254
TI  - A Novel Prediction Model for Postmolar Gestational Trophoblastic Neoplasia and
      Comparison With Existing Models.
AB  - OBJECTIVE: The aim of this study was to comparatively study a novel model and
      existing models of predicting postmolar gestational trophoblastic neoplasia
      (GTN). METHODS: Two hundred twenty-two patients with complete hydatidiform moles
      were enrolled retrospectively. A natural regression was noted in 195 patients
      (spontaneous regression group), whereas the remaining 27 patients entered
      postmolar GTN (postmolar GTN group). The upper limits of the 95% confidence
      interval of human chorionic gonadotropin (hCG) values and hCG regression rates
      were calculated aggregately from the spontaneous regression group. The 4
      prediction models (weekly hCG regression curve and weekly hCG regression rate
      curve reported by previous studies; daily hCG regression curve and daily hCG
      regression rate curve pioneered by us) were then plotted. The individual hCG
      curve of the postmolar GTN group was plotted and compared with the prediction
      models, respectively. The individual hCG curve superimposing the prediction curve
      was considered showing an elevated risk of GTN. RESULTS: All patients with
      postmolar GTN were preidentified by daily hCG regression rate curve. The other 3
      prediction models had a considerable rate of failure in identification. Mean
      diagnosis time of daily hCG regression rate curve was significantly lower (P =
      0.008), with an average of 15.3 days gained compared with International
      Federation of Gynecology and Obstetrics criteria. Cochran Q test showed that
      daily hCG regression rate curve produced a significantly better performance in
      predicting postmolar GTN than weekly hCG regression curve (P = 0.01).
      CONCLUSIONS: Our data showed that daily hCG regression rate curve gives a better
      prediction of postmolar GTN and might potentially enhance the monitoring of
      patients with molar pregnancy, especially those who could not adhere to
      International Federation of Gynecology and Obstetrics protocols. However, this
      preliminary research should not change current clinical practice until further
      validation is carried out.

PMID- 28498255
TI  - The Significance of VSIG4 Expression in Ovarian Cancer.
AB  - OBJECTIVES: The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7
      family-related macrophage protein with the capacity to inhibit T-cell activation,
      has a potential role in cancer. Here we suggest its possibility as a therapeutic
      target and prognostic biomarker of ovarian cancer. METHODS: Between January 2011
      and June 2015, tumor tissues and peripheral blood samples were obtained during
      surgery from 10 patients with benign ovarian tumors and 22 patients with ovarian
      cancers. Messenger RNA and protein expression levels of VSIG4 in benign tumor and
      cancer tissues were examined by the reverse transcription polymerase chain
      reaction and Western blot, respectively. Soluble VSIG4 concentrations were
      measured by an enzyme-linked immunosorbent assay. The correlation between VSIG4
      expression and the prognosis of ovarian cancer was analyzed according to the
      patients' clinicopathologic characteristics. RESULTS: VSIG4 messenger RNA and
      protein expression levels in ovarian cancer tissues were higher than those in
      benign ovarian tumors (P = 0.0013 and 0.0001, respectively). Soluble VSIG4
      concentrations were increased in patients with ovarian cancer compared with that
      in patients with benign ovarian tumors (P = 0.0452). Moreover, soluble VSIG4
      levels were significantly increased in advanced-stage and recurrent ovarian
      cancer (P = 0.0244 and 0.0288, respectively). High VSIG4 expression of cancer
      tissue and low VSIG4 expression of plasma (soluble VSIG4) were associated with a
      longer disease-free interval (P = 0.0246 and 0.0398, respectively). CONCLUSIONS:
      VSIG4 is overexpressed in ovarian cancers compared with that in benign tumors.
      This finding supports VSIG4 being used as a potential therapeutic target for
      ovarian cancer. Furthermore, soluble VSIG4 levels are associated with the
      progression and recurrence of ovarian cancer, indicating that soluble VSIG4 may
      be used as a potential biomarker for predicting tumor prognosis.

PMID- 28498257
TI  - The Addition of Adjuvant Chemotherapy to Radiation in Early-Stage High-Risk
      Endometrial Cancer: Survival Outcomes and Patterns of Care.
AB  - OBJECTIVE: Early-stage high-risk endometrial cancer (HREC) treated with adjuvant
      radiotherapy (aRT) alone has been associated with an increased risk of distant
      relapse. The addition of chemotherapy to radiotherapy (aCRT) may benefit overall
      survival (OS). We investigated the patterns-of-care and OS benefit of aCRT in
      HREC by analyzing a large national registry. METHODS: Our query was limited to
      patients with the International Federation of Gynecology and Obstetrics stage IB
      and II HREC with either papillary serous, clear cell, or grade 3 adenocarcinoma,
      diagnosed between 2004 and 2012. Logistic and Cox regression analyses were
      utilized to identify predictors of aCRT use and OS, respectively. Survival
      analysis was performed with Kaplan Meier and log-rank methods. Propensity score
      matching was employed to decrease the potential influence of selection bias.
      RESULTS: A total of 11,746 patients were identified for analysis with 8206
      (69.9%) receiving aCRT, and 3540 (30.1%) received aRT. Predictors of aCRT
      included International Federation of Gynecology and Obstetrics stage II (odds
      ratio [OR], 1.39; 95% confidence interval [CI], 1.22-1.57), papillary serous (OR,
      9.44; 95% CI, 8.22-10.85) or clear cell (OR, 3.21; 95% CI, 2.59-3.97) histology,
      lymph nodes removed (OR, 1.48; 95% CI, 1.31-1.69), and receipt of brachytherapy
      alone (OR, 1.55; 95% CI, 1.36-1.78). Estimated 5-year OS was 75.2% for patients
      receiving aRT only and 79.2% for those receiving aCRT (P < 0.001). When compared
      with aRT, aCRT was associated with improved OS on multivariate (hazard ratio,
      0.78; 95% CI, 0.61-0.99) analysis. A univariate shared-frailty Cox regression
      after propensity score matching revealed persistence of the OS benefit with aCRT
      (hazard ratio, 0.74; 95% CI, 0.65-0.84). CONCLUSIONS: The addition of adjuvant
      chemotherapy to radiation in HREC is associated with improved OS. Multiple
      demographic and clinical factors significantly influence the choice of adjuvant
      therapy in this setting.

PMID- 28498256
TI  - Paragon (ANZGOG-0903): Phase 2 Study of Anastrozole in Women With Estrogen or
      Progesterone Receptor-Positive Platinum-Resistant or -Refractory Recurrent
      Ovarian Cancer.
AB  - BACKGROUND: There is some evidence that a subset of patients with recurrent
      ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a
      basket protocol that includes a series of phase 2 trials investigating the
      activity of anastrozole in patients with estrogen or progesterone receptor
      positive recurrent gynecological cancers. We report the results of treatment in
      patients with platinum-resistant or -refractory recurrent epithelial ovarian
      cancer. METHODS: Postmenopausal women who had estrogen and/or progesterone
      receptor-positive platinum-resistant or platinum-refractory recurrent ovarian
      cancer and disease measurable by Response Evaluation Criteria In Solid Tumors
      (RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were
      eligible. Patients received anastrozole 1 mg daily until progression or
      unacceptable toxicity. The study was prospectively registered
      (ACTRN12610000796088). RESULTS: There were 49 evaluable patients, and clinical
      benefit was observed in 13 (27%; 95% confidence interval [CI], 16%-40%). There
      were no complete or partial RECIST version 1.1 responses. Clinical benefit was
      associated with higher global quality-of-life scores. Median progression-free
      survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical
      benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed
      within 6 months. Seven patients continued on treatment for longer than 6 months.
      Anastrozole was well tolerated in most patients. Subgroup analysis suggested
      greater clinical benefit in patients with tumors with estrogen-receptor
      histoscore of more than 200, but this difference was not statistically
      significant. CONCLUSIONS: A subset of patients with estrogen- or progesterone
      positive platinum-resistant or platinum-refractory recurrent epithelial ovarian
      cancers derives clinical benefit from anastrozole, with acceptable toxicity. The
      challenge remains how to identify them.

PMID- 28498258
TI  - Evaluation and Selection of Quality Indicators for the Management of Endometrial
      Cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate 36 quality indicators (QIs) for
      monitoring the quality of care of uterine cancer to be implemented in the EFFECT
      (effectiveness of endometrial cancer treatment) project. METHODS: The 36 QIs were
      evaluated in the first 10 patients diagnosed with endometrial cancer and managed
      in 14 French hospitals in 2011. To assess the status of each QI, a questionnaire
      detailing the 36 QIs was sent to each hospital, and the information was cross
      checked with information from the multidisciplinary staff meeting, surgical
      reports, and pathological reports. The QIs were evaluated in terms of
      measurability and improvability. The remaining QIs were evaluated with a multiple
      correspondence analysis to highlight the interrelationships between qualitative
      variables describing a population. RESULTS: Thirteen of the 14 institutions
      responded to the survey for a total of 130 patients. Twenty-five of the 36 QIs
      affected less than 80% of the patients. Thirteen QIs were found not to be
      improvable because they reached more than 95% of the theoretical target. Finally,
      5 QIs concerning more than 80% of the patients were found to be improvable. The
      multiple correspondence analysis finally identified 3 dimensions-outcome, safety,
      and perioperative management-that included the 5 QIs. CONCLUSIONS: In the present
      study, 5 of the 36 QIs suggested by the EFFECT project seem to be sufficient to
      report on the quality of endometrial cancer management. Further studies are
      needed to correlate the information provided by those 5 questions and the
      relevant outcomes reflecting quality of care in endometrial cancer.

PMID- 28498259
TI  - Efficacy of Pegylated Liposomal Doxorubicin in Low-Grade Serous Ovarian
      Carcinoma.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of pegylated
      liposomal doxorubicin (PLD) in low-grade serous ovarian carcinoma (LGSOC).
      METHODS: We retrospectively identified patients with LGSOC who were treated with
      PLD. Response to therapy was evaluated by RECIST 1.1 criteria. Progression-free
      survival (PFS) and overall survival were calculated. In addition, PFS on PLD was
      compared with the patient's most recent PFS on previous therapy. RESULTS: Twenty
      four patients were treated with PLD. Three patients were not evaluable, leaving
      21 patients evaluable for response. Pegylated liposomal doxorubicin was dosed at
      40 mg/M every 28 days except in 7 patients (5 received PLD dosed at 30 mg/M in
      combination with carboplatin and 2 received PLD dosed at 20 mg/M, one of which
      was in combination with etoposide). Four of the patients who received PLD in
      combination subsequently received PLD alone for 4+, 12, 21, and 29 cycles,
      respectively. Three patients (14.3%) had a complete response and remained
      progression free at 8, 31, and 34 months, respectively. Two of these patients
      received PLD alone. The third complete response patient initially received PLD in
      combination with carboplatin and then went on to receive PLD alone during which a
      complete radiologic response was achieved. No difference in response or PFS by
      platinum sensitivity was noted (Ps = 0.73 and 0.62, respectively). Fourteen
      patients had stable disease for a median of 18 months. Among the 14 patients with
      stable disease, the PFS on PLD exceeded the previous PFS in 11 patients (78.6%)
      from 1.3 to 20.6 folds, with a median of 3.5 folds. The 2 of the 3 lowest
      increases in PFSs were seen in patients whose therapy was terminated despite
      stable disease. CONCLUSIONS: Pegylated liposomal doxorubicin is relatively active
      in LGSOC. The treatment of stable disease resulted in increase in PFS in 78.6% of
      patients by a mean of 350%.

PMID- 28498260
TI  - Combined Gene Therapy Using AdsVEGFR2 and AdsTie2 With Chemotherapy Reduces the
      Growth of Human Ovarian Cancer and Formation of Ascites in Mice.
AB  - OBJECTIVES: Ovarian cancer is highly dependent on tumor microvessels and
      angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their
      receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied
      the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2
      combined with paclitaxel and carboplatin for the treatment of ovarian cancer.
      METHODS: An intraperitoneal human ovarian cancer xenograft model in nude mice (n
      = 44) was used in this study. Gene therapy was given intravenously when the
      presence of sizable tumors was confirmed in magnetic resonance imaging. The study
      groups were as follows: AdCMV as a control (group I), AdCMV with chemotherapy
      (group II), AdsVEGFR2 and AdsTie2 (group III), and AdsVEGFR2 and AdsTie2 with
      chemotherapy (group IV). Antitumor effectiveness was assessed by overall tumor
      growth, ascites, immunohistochemistry, microvessel density, and sequential
      magnetic resonance imaging analyses. RESULTS: AdsVEGFR2 and AdsTie2 gene therapy
      (group III) significantly reduced tumor weights as compared with group II (P =
      0.007). Accumulation of ascites was significantly reduced when the mice were
      treated with AdsVEGFR2 and AdsTie2 gene therapy or with combined gene therapy and
      chemotherapy as compared with controls (P = 0.029 and P = 0.010, respectively).
      Vascular endothelial growth factor and Ang2 levels in ascites fluid were elevated
      after the gene therapy. CONCLUSIONS: Combined inhibition of VEGF/VEGFR2 and
      Ang/Tie2 pathways provided efficient therapy for ovarian cancer in mice. In
      addition, antiangiogenic gene therapy has potential as a treatment for the
      accumulation of ascites.

PMID- 28498261
TI  - Clear Cell Carcinoma of the Uterine Cervix: A Clinical and Pathological Analysis
      of 47 Patients Without Intrauterine Diethylstilbestrol Exposure.
AB  - OBJECTIVES: The aim of this study was to summarize the clinical and pathological
      characteristics and to conduct prognosis analysis of patients who were diagnosed
      with clear cell carcinoma of the uterine cervix (CCCUC) and without a history of
      exposure to diethylstilbestrol. METHODS: We performed a retrospective review of
      all the patients with CCCUC who were diagnosed and treated at Zhejiang Cancer
      Hospital between 1998 and 2014. Charts were reviewed for clinical and
      pathological characteristics, and prognosis analysis was conducted. RESULTS: A
      total of 47 patients were included. Median age was 52 years. No patient had a
      history of exposure to diethylstilbestrol. The International Federation of
      Gynecology and Obstetrics stage distribution was 55.3% (n = 26) stage I, 40.4% (n
      = 19) stage II, 2.1% (n = 1) stage III, and 2.1% (n = 1) stage IV. Forty-two
      patients (89.4%) underwent radical hysterectomy and pelvic lymphadenectomy.
      Pathological examination revealed deep cervical stromal invasion (greater than
      two thirds) in 20 patients (48.4%), pelvic lymph node (PLN) metastasis in 10
      patients (23.8%), lymphovascular space involvement in 9 patients (21.4%), and
      ovarian metastasis in 1 patient (2.4%). Advanced tumor stage (IIB-IV), larger
      tumor size (>4 cm), and PLN metastasis had negative effects on progression-free
      survival (PFS) and overall survival (OS) (P < 0.05). Adjuvant radiation therapy
      alone or concurrent chemoradiation therapy after radical surgery did not affect
      PFS or OS in patients with risk factors (P > 0.05). CONCLUSIONS: International
      Federation of Gynecology and Obstetrics stage, tumor size, and PLN status were
      prognostic factors for both PFS and OS in patients with CCCUC. The long-term
      effects of adjuvant radiation therapy or concurrent chemoradiation therapy may be
      limited for CCCUC patients with risk factors. Future larger case series or
      clinical trials are required to confirm these findings.

PMID- 28498262
TI  - Sarcoma Risk in Uterine Surgery in a Tertiary University Hospital in Germany.
AB  - OBJECTIVES: There is a risk to incidentally spread uterine malignancies,
      especially sarcoma, if tissue is morcellated during hysterectomy or myoma
      enucleation. In the last years, a worldwide discussion has been started about
      this problem. However, the risk seems to be very small in recent studies. This
      study aims at further investigating the risk of disseminating uterine malignancy
      during uterine surgery in a tertiary university hospital in Germany. METHODS: In
      a retrospective setting, all cases of uterine myometrial surgery (hysterectomies
      and myomectomies) in our clinic during a period of 10 years were identified using
      clinical databases. Histology was linked and searched for uterine malignancies.
      All cases were reviewed for incidental morcellation of malignant tissue. RESULTS:
      Between 2004 and 2014, we identified 2825 cases of uterine myometrial surgery.
      Morcellating procedures were used in 20% of the 1402 hysterectomy procedures
      (280/1402) and in 13.7% of the 1423 fibroid removals (195/1423). We identified 23
      uterine mesenchymal malignancies (sarcoma, n = 10; carcinosarcoma, n = 13). In 3
      cases, there was no evidence or sign of a malignant disease preoperatively in a
      procedure with a morcellation (vaginal hysterectomy with morcellation, n = 1;
      open fibroid enucleation, n = 2). CONCLUSIONS: A small risk (0.35% [1/280]) of
      accidental morcellation during hysterectomy with morcellation was found in our
      study. We did not observe an occult case of sarcoma after myomectomy with
      morcellation (0/195), but we found 2 cases of accidental sarcoma after myomectomy
      without morcellation. For these reasons, minimally invasive surgery with
      morcellation should not be excluded a priori. The patient should be well informed
      about the risks and various options. The advantage of laparoscopic surgery should
      be balanced against the risk of the unknown spread of malignant tissue.

PMID- 28498264
TI  - Defining the Hook Region Anatomy of the Guinea Pig Cochlea for Modeling of Inner
      Ear Surgery.
AB  - HYPOTHESIS: The aim of this study was to describe the hook region anatomy of the
      guinea pig cochlea to identify the optimal surgical approach for cochlear
      implantation and to determine what anatomical structures are at risk. BACKGROUND:
      Animal studies investigating hearing loss after cochlear implantation surgery are
      currently constrained by the lack of a reproducible implantation model. METHODS:
      Guinea pig cochleae were imaged using thin-sheet laser imaging microscopy. Images
      were stitched, reconstructed, and segmented for analysis. Insertion vectors were
      determined by tracing their paths to the outer wall and converting to Cartesian
      coordinates. Spherical surface and multiplane views were generated to analyze
      outer wall and radial forces of the insertion vector. RESULTS: Thin-sheet laser
      imaging microscopy enabled quantitative, whole specimen analysis of the soft and
      bony tissue relationships of the complex cochlear hook region in any desired
      plane without loss of image quality. Round window or cochleostomy approaches in
      the anteroinferior plane avoided direct damage to cochlear structures.
      Cochleostomy approach had large interindividual variability of angular depth and
      outer wall forces but predictable radial force. CONCLUSION: The guinea pig hook
      region and lower basal turn have similar structural relationships to humans.
      Careful cochleostomy placement is essentially for minimizing cochlear trauma and
      for ensuring a straight insertion vector that successfully advances around the
      outer wall. Experiments with guinea pigs that control for the surgical approach
      are likely to provide useful insights into the aetiology and the development of
      therapies directed at postimplantation hearing loss.

PMID- 28498263
TI  - Cochlear Implantation in Patients With Usher Syndrome Type IIa Increases
      Performance and Quality of Life.
AB  - OBJECTIVES: Usher syndrome type IIa (USH2a) is characterized by congenital
      moderate to severe hearing impairment and retinitis pigmentosa. Hearing
      rehabilitation starts in early childhood with the application of hearing aids. In
      some patients with USH2a, severe progression of hearing impairment leads to
      insufficient speech intelligibility with hearing aids and issues with adequate
      communication and safety. Cochlear implantation (CI) is the next step in
      rehabilitation of such patients. This study evaluates the performance and benefit
      of CI in patients with USH2a. DESIGN: Retrospective case-control study to
      evaluate the performance and benefit of CI in 16 postlingually deaf adults (eight
      patients with USH2a and eight matched controls). Performance and benefit were
      evaluated by a speech intelligibility test and three quality-of-life
      questionnaires. RESULTS: Patients with USH2a with a mean age of 59 years at
      implantation exhibited good performance after CI. The phoneme scores improved
      significantly from 41 to 87% in patients with USH2a (p = 0.02) and from 30 to 86%
      in the control group (p = 0.001). The results of the questionnaire survey
      demonstrated a clear benefit from CI. There were no differences in performance or
      benefit between patients with USH2a and control patients before and after CI.
      CONCLUSIONS: CI increases speech intelligibility and improves quality of life in
      patients with USH2a.

PMID- 28498265
TI  - The Effect of Systemic Steroid on Hearing Preservation After Cochlear
      Implantation via Round Window Approach: A Guinea Pig Model.
AB  - HYPOTHESIS: When administered perioperatively, systemic dexamethasone will reduce
      the hearing loss associated with cochlear implantation (CI) performed via the
      round window approach. BACKGROUND: The benefits of electroacoustic stimulation
      have led to interest in pharmacological interventions to preserve hearing after
      CI. METHODS: Thirty guinea pigs were randomly divided into three experimental
      groups: a control group; a 3-day infusion group; and a 7-day infusion group.
      Dexamethasone was delivered via a mini-osmotic pump for either 3 or 7 days after
      CI via the round window. Pure tone-evoked auditory brainstem response (ABR)
      thresholds were monitored for a period of 12 weeks after CI. The cochleae were
      then collected for histology. RESULTS: At 4 and 12 weeks after CI, ABR threshold
      shifts were significantly reduced in both 7-day and 3-day infusion groups
      compared with the control group. Furthermore, the 7-day infusion group has
      significantly reduced ABR threshold shifts compared with the 3-day infusion
      group. The total tissue response, including fibrosis and ossification, was
      significantly reduced in the 7-day infusion group compared with the control
      group. On multiple regression the extent of fibrosis predicted hearing loss
      across most frequencies, while hair cell counts predicted ABR thresholds at 32
      kHz. CONCLUSION: Hearing protection after systemic administration of steroids is
      more effective when continued for at least a week after CI. Similarly, this
      treatment approach was more effective in reducing the fibrosis that encapsulates
      the CI electrode. Reduced fibrosis seemed to be the most likely explanation for
      the hearing protection.

PMID- 28498266
TI  - Use of Positive Airway Pressure Following Middle Ear Surgery: A Practice Survey
      of Otologists.
AB  - BACKGROUND: Positive airway pressure (PAP) devices are used as treatment for
      obstructive sleep apnea (OSA). PAP may increase middle ear pressure which is of
      interest to otologic surgeons. There is a lack of data to guide management of PAP
      therapy after middle ear surgery. OBJECTIVE: To elucidate how otologic surgeons
      manage PAP in their patients after ear surgery. STUDY DESIGN: A survey e-mailed
      to practicing members of the American Neurotology Society. RESULTS: Among 60
      respondents, the most common recommendations to patients were to avoid PAP use
      for 1 week (40%), return to normal use immediately (23.3%), avoid PAP for 1 month
      (13.3%), or avoid PAP for 1 day (13.3%) after surgery. Twenty percent of
      providers reported that they change their advice on the basis of the PAP pressure
      settings (i.e., shorter hiatus for higher settings). Among respondents, 47% think
      that they have patients with middle ear issues because of PAP and 13% attributed
      surgical failures to PAP use. One-third of providers routinely pack the
      Eustachian tube during surgery. Providers who attributed a negative surgical
      outcome to PAP use were more likely to routinely pack/plug the Eustachian tube
      during otologic surgery (p = 0.001). CONCLUSION: Treatment recommendations
      regarding postoperative PAP treatment for obstructive sleep apnea vary greatly
      among practicing otologists. Providers who think that an adverse outcome was
      attributed to PAP use were more likely to prophylactically plug the Eustachian
      tube during surgery. Future research will provide additional information which
      will allow a better understanding of the effect of PAP on the middle ear,
      especially after otologic surgery.

PMID- 28498267
TI  - Endoscopic Infracochlear Approach for Drainage of Petrous Apex Cholesterol
      Granulomas: A Case Series.
AB  - OBJECTIVE: To describe the feasibility and technical nuances of a transcanal
      endoscopic infracochlear approach for drainage of petrous apex cholesterol
      granulomas. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care
      university hospital. PATIENTS: A 32-year-old man with bilateral petrous apex
      cholesterol granulomas and a 54-year-old man with a left-sided petrous apex
      granuloma each with symptoms necessitating surgical intervention. INTERVENTIONS:
      Transcanal endoscopic infracochlear approach for drainage of the cholesterol
      granulomas. MAIN OUTCOME MEASURES: Operation efficacy, corridor size, and
      perioperative morbidity. RESULTS: All three cholesterol granulomas were
      successful drained without violating the cochlea, jugular bulb, or carotid
      artery. The dimensions of the infracochlear surgical corridor measured 5 mm * 6
      mm, 3.5 mm * 3.5 mm, and 6 mm * 4 mm, respectively. All corridors facilitated
      visualization within the cyst and allowed lyses of adhesions for additional cyst
      content eradication. All patients had resolution of their acute symptoms. Two of
      the three subjects had serviceable hearing before and after their procedures. One
      patient required revision surgery 2-months after their initial procedure
      secondary to recurrent symptoms from acute hemorrhage within the cyst cavity. The
      infracochlear tract in this patient was noted to be patent. CONCLUSIONS: A
      transcanal endoscopic infracochlear approach is feasible for the management of
      cholesterol granuloma. The surgical access was wide enough to introduce the
      endoscope into the petrous apex cavity in each case. Further studies are needed
      to compare the efficacy and perioperative morbidity versus the traditional
      postauricular transtemporal approaches.

PMID- 28498268
TI  - Transcanal Endoscopic Ear Surgery for Excision of a Facial Nerve Venous
      Malformation With Interposition Nerve Grafting: A Case Report.
AB  - OBJECTIVE: To illustrate a novel approach for the surgical management of a venous
      malformation of the facial nerve, including interposition nerve grafting, via an
      exclusively transcanal endoscopic ear surgery (TEES) approach. PATIENT: Thirty
      nine-year-old woman with a preoperative House-Brackmann (HB) grade IV facial
      paresis secondary to a facial nerve tumor. INTERVENTION(S): Surgical excision and
      interposition nerve graft via a transcanal endoscopic approach. MAIN OUTCOME
      MEASURE(S): Completeness of resection, approach morbidities, and facial nerve
      outcome. RESULTS: The TEES approach provided wide exposure of the facial nerve
      from the geniculate ganglion through the mastoid segment. This visualization
      facilitated gross total tumor resection, incus interposition ossicular
      reconstruction, and placement of an interposition nerve graft. The nerve graft
      was positioned in the fallopian canal and was secured at both ends with surgicel.
      The patient had no postoperative complications. At 11-month follow-up her facial
      function had returned to HB grade IV. CONCLUSIONS: This is the first report of
      resecting a venous malformation of the facial nerve with concomitant
      interposition nerve graft reconstruction via an exclusively endoscopic approach.
      This report adds to the growing body of evidence that TEES can manage diverse
      middle ear and lateral skull base pathology. Additional studies are needed to
      fully elucidate the risk-benefit profile of this technique.

PMID- 28498269
TI  - Real-Time Intracochlear Electrocochleography Obtained Directly Through a Cochlear
      Implant.
AB  - HYPOTHESIS: Utilizing the cochlear implant to record electrophysiologic responses
      during device placement is a feasible and efficacious technique for monitoring
      near real-time cochlear physiology during and following electrode insertion.
      BACKGROUND: Minimizing intracochlear trauma during cochlear implantation has
      emerged as a highly researched area to help improve patient performance.
      Currently, conventional cochlear implant technology allows for the recording of
      electrically evoked compound action potentials (eCAPs). Acoustically evoked
      potentials may be more sensitive in detecting physiologic changes occurring as a
      result of electrode insertion. Electrocochleography obtained from within the
      cochlea allows hair cell and neural response monitoring along the cochlear spiral
      at locations where changes most likely would occur. METHODS: Intracochlear
      electrocochleography (ECochG) was recorded from the cochlear implant during
      surgery in 14 subjects. A long acquisition time (54.5 ms), capable of measuring
      potentials from the low frequency-serving apical region of the cochlea (125 and
      500 Hz) was employed. Two distinct intracochlear processing methods were used and
      compared in obtaining electrophysiologic data. RESULTS: Measureable intracochlear
      ECochG responses were obtained from all 14 participants. The 1st harmonic
      distortions (cochlear microphonic and auditory nerve neurophonic) generally
      increased steadily with electrode insertion. Electrode and frequency scan
      following insertion revealed that response amplitude varied based on location of
      recording electrode and frequency of stimulation. Exquisite sensitivity to
      manipulation during round window muscle packing was demonstrated. CONCLUSION:
      Intracochlear ECochG recorded from the electrode array of the cochlear implant is
      a highly feasible technique that sheds light on cochlear micromechanics during
      cochlear implant electrode placement.

PMID- 28498270
TI  - Age-Related Increase in Blood Levels of Otolin-1 in Humans.
AB  - OBJECTIVE: To test the hypothesis that age-related demineralization of otoconia
      will result in an age-related increase in blood levels of otoconia matrix
      protein, otolin-1. STUDY DESIGN: Cross-sectional observational clinical trial.
      SETTING: Clinical research center. PATIENTS: Seventy nine men and women ranging
      in age from 22 to 95 years old. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES:
      Blood levels of otolin-1 in relation to age. RESULTS: Levels of otolin-1 of
      subjects divided into four age groups (1: 20-30 [n = 20], 2: 50-65 [n = 20], 3:
      66-80 [n = 20], 4: 81-95 [n = 19] years old) demonstrated an increasing trend
      with age. The difference between otolin levels of groups 2 and 3, as well as, (p
      = 0.04) and 2 and 4 (p = 0.031) were statistically significant, but there was no
      significant difference between the two oldest groups. CONCLUSIONS: Otolin-1 blood
      levels are significantly higher in patients older than 65 years of age. This is
      consistent with previous scanning electron microscopy findings of age-related
      otoconia degeneration and increased prevalence of benign paroxysmal positional
      vertigo (BPPV) with age. Normative data provided here can serve as important
      reference values against which levels from BPPV patients can be compared with
      further evaluate otolin-1 as a circulatory biomarker for otoconia degeneration.

PMID- 28498271
TI  - Epidemiology of Dizzy Patient Population in a Neurotology Clinic and Predictors
      of Peripheral Etiology.
AB  - OBJECTIVE: To compare the proportion of peripheral versus nonperipheral dizziness
      etiologies among all patients, inclusive of those presenting primarily or as
      referrals, to rank diagnoses in order of frequency, to determine whether or not
      age and sex predict diagnosis, and to determine which subgroups tended to undergo
      formal vestibular testing. STUDY DESIGN: Retrospective cohort. SETTING: Academic
      neurotology clinic. PATIENTS: Age greater than 18 neurotology clinic patients
      with the chief complaint of dizziness. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Age, sex, diagnosis, record of vestibular testing. RESULTS: Two
      thousand seventy-nine patients were assigned 2,468 diagnoses, of which 57.7 and
      42.3% were of peripheral and nonperipheral etiologies, respectively. The most
      common diagnoses were Meniere's (23.0%), vestibular migraine (19.3%), benign
      paroxysmal positional vertigo (BPPV) (19.1%), and central origin, nonmigraine
      (16.4%). Peripheral diagnoses are more likely to be found in men than in women
      (odds ratio [OR] 1.59). Peripheral diagnoses were most likely to be found in the
      60 to 69 age group (OR 3.82). There was not a significant difference in rate of
      vestibular testing between women and men. Among patients with two diagnoses, the
      most common combinations were vestibular migraine and BPPV then vestibular
      migraine and Meniere's. CONCLUSIONS: A large proportion of patients seen for the
      chief complaint of dizziness in the neurotology clinic were found not to have a
      peripheral etiology of their symptoms. These data challenge a prevalent dogma
      that the most common causes of dizziness are peripheral: BPPV, vestibular
      neuritis, and Meniere's disease. Age and sex are statistically significant
      predictors of peripheral etiology of dizziness.

PMID- 28498272
TI  - Paget's Disease of the Temporal Bone: A Single-Institution Contemporary Review of
      27 Patients.
AB  - OBJECTIVES: To report a contemporary review from a single-institution series on
      Paget's disease of the temporal bone (PDTB). STUDY DESIGN: Retrospective chart
      review of patients evaluated from 1998 to 2016. SETTING: Quaternary referral
      center. PATIENTS: Patients with radiographically confirmed PDTB. MAIN OUTCOME
      MEASURES: Clinical, audiological, and radiological features and management
      strategies of PDTB. RESULTS: A total of 50 temporal bones in 27 patients (15 men)
      were diagnosed with PDTB. Symptoms at presentation included hearing loss (n = 23,
      85%), headache (n = 18, 67%), dizziness (n = 14, 52%), tinnitus (n = 5, 19%),
      chronic otitis media (n = 2, 7%), hemifacial spasm without facial paralysis (n =
      1, 4%), multiple cranial neuropathies (n = 1, 4%), and neoplastic transformation
      (n = 1, 4%). Of the 23 ears with audiometric data available for review, 65%
      exhibited sensorineural hearing loss, and 35% mixed hearing loss. Long-term
      audiometric follow-up was available on two patients, both of whom demonstrated
      hearing loss at a rate greater than would be expected for normal aging. Two
      patients underwent successful cochlear implantation, achieving open-set speech
      recognition. Radiographic features of temporal bone involvement are reviewed and
      illustrated. CONCLUSION: This is the largest single-institution clinical series
      examining patients with PDTB in the English literature. Variable patterns of
      temporal bone involvement by Paget's disease are observed leading to a diverse
      set of clinical symptoms, including slowly progressive hearing loss, tinnitus,
      compressive cranial neuropathies, and benign or malignant tumorigenesis.
      Involvement typically begins in the petrous apex and progresses laterally. Otic
      capsule bone demineralization occurs late in the disease process. Cochlear
      implantation appears to be an effective management strategy for patients with
      severe-to-profound hearing loss.

PMID- 28498275
TI  - Influence of Acute Multispecies and Multistrain Probiotic Supplementation on
      Cardiovascular Function and Reactivity to Psychological Stress in Young Adults: A
      Double-Blind, Randomized, Placebo-Controlled Trial.
AB  - OBJECTIVE: The potential influence of probiotic supplementation on cardiovascular
      health and stress responsivity remains largely unexplored. Some evidence suggests
      the possibility that probiotics may influence blood pressure. A separate body of
      research suggests that exaggerated cardiovascular reactions to acute
      psychological stress in the laboratory predict cardiovascular morbidity and
      mortality. The current investigation explored the effect of acute probiotic use
      on (1) resting cardiovascular measures in healthy young adults and (2)
      cardiovascular and psychological reactions to an acute psychological stressor in
      the laboratory. METHOD: Participants (N = 105, M [SD] age = 20.17 [1.26], 84.8%
      white) completed a 2-week, double-blind, and placebo-controlled trial of a
      multispecies and multistrain probiotic. Exclusion criteria included previous
      probiotic use, diagnosed gastrointestinal disorder, and/or current antibiotic
      use. At visits 1 and 2, participants completed the Paced Auditory Serial Addition
      Test, a widely used psychological stress task. Participants were randomly
      assigned to a probiotic blend or matched placebo. RESULTS: Compared with placebo,
      2-week probiotic supplementation did not affect resting measures of
      cardiovascular function, cardiovascular responses during or recovery from stress,
      or psychological reactions to acute psychological stress. CONCLUSIONS: Contrary
      to expectations, short-term use of a probiotic supplement in healthy participants
      did not influence measures of cardiovascular function or responsivity to
      psychological stress. Future research is needed to determine species- and strain
      specific effects of probiotics in healthy participants with various degrees of
      stress responsiveness, as well as in diseased populations.

PMID- 28498274
TI  - Fornix Structural Connectivity and Allostatic Load: Empirical Evidence From
      Schizophrenia Patients and Healthy Controls.
AB  - OBJECTIVE: The fornix is a white matter tract carrying the fibers connecting the
      hippocampus and the hypothalamus, two essential stress-regulatory structures of
      the brain. We tested the hypothesis that allostatic load (AL), derived from a
      battery of peripheral biomarkers indexing the cumulative effects of stress, is
      associated with abnormalities in brain white matter microstructure, especially
      the fornix, and that higher AL may help explain the white matter abnormalities in
      schizophrenia. METHODS: Using 13 predefined biomarkers, we tested AL in 44
      schizophrenic patients and 33 healthy controls. Diffusion tensor imaging was used
      to obtain fractional anisotropy (FA) values of the fornix and other white matter
      tracts. RESULTS: AL scores were significantly elevated in patients compared with
      controls (F(3,77) = 7.87, p = .006). AL was significantly and inversely
      correlated with FA of fornix in both controls (r = -.58, p = .001) and patients
      (r = -.36, p = .023). Several nominally significant (p < .05 but did not survive
      Bonferroni correction for multiple comparison) correlations were also observed
      between AL and FA of other white matter tracts in schizophrenic patients.
      However, the fornix was the only tract exhibiting a correlation with AL in both
      groups. CONCLUSIONS: These results provide initial evidence that allostatic
      processes are linked to fornix microstructure in clinical participants.

PMID- 28498276
TI  - Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal
      Distension in Patients With Irritable Bowel Syndrome.
AB  - OBJECTIVE: We investigated whether certainty and uncertainty of impending
      aversive visceral sensation differently modulate regional brain activity, both
      during anticipation and visceral sensation in irritable bowel syndrome (IBS)
      patients compared with healthy controls. METHODS: Twenty-six IBS patients (14
      women) and 29 healthy controls (15 women) were enrolled in a functional magnetic
      resonance imaging study. Participants received rectal distention at an
      individually titrated severe discomfort level that was preceded by visual cues to
      induce certain (100% chance of distention), uncertain (50% chance), and safe (0%
      chance) anticipation. RESULTS: Subjective ratings of anticipatory fear before and
      discomfort during distention were similar between IBS and control participants
      under cued certainty and uncertainty (p > .05). Uncertain anticipation compared
      with certain anticipation induced greater activation of anterior midcingulate
      cortex, thalamus, and visual processing areas in IBS patients compared with
      controls. Rectal distention after the uncertain, but not certain, cue induced
      higher activity in the posterior- and midcingulate cortices and the precuneus in
      IBS compared with controls. Controls exhibited bilateral insula activation during
      the nondistention period after the uncertain cue compared with the safe cue. IBS
      patients failed to produce this response, which was possibly due to elevated
      bilateral insular responses during nondistention after the safe cue. Brain data
      were significant at a voxel-level threshold of puncorrected value of less than
      .005 combined with a cluster-level threshold of pFWE-corrected value of less than
      .05. CONCLUSIONS: Preceding uncertainty differentially modulates the brain
      processing of physiologically identical rectal stimulation in IBS patients. Cue
      dependent alterations in brain responses may underlie hypervigilance to visceral
      sensations in IBS patients.

PMID- 28498277
TI  - Influence of Visceral Interoceptive Experience on the Brain's Response to Food
      Images in Anorexia Nervosa.
AB  - OBJECTIVE: The aim of the study was to determine how visceral sensations affect
      responses to food stimuli in anorexia nervosa (AN). METHODS: Twenty weight
      restored, unmedicated adolescent and young adult women with AN and twenty healthy
      control participants completed an interoceptive attention task during which they
      focused on sensations from the heart, stomach, and bladder and made ratings of
      these sensations. They then underwent functional magnetic resonance imaging
      scanning while viewing pictures of food and nonfood objects. Between-groups t
      tests were employed to investigate group differences in the relationship between
      interoceptive sensation ratings and brain hemodynamic response to food pictures
      and, specifically, to highly palatable foods. RESULTS: In response to food
      pictures, AN participants exhibited a positive relationship between stomach
      sensation ratings and posterior insula activation (peak t = 4.30). AN
      participants displayed negative relationships between stomach sensation ratings
      and amygdala activation (peak t = -4.05) and heart sensation ratings and
      ventromedial prefrontal cortex activation (peak t = -3.52). In response to highly
      palatable foods, AN was associated with positive relationships between stomach
      sensation ratings and activity in the subgenual anterior cingulate (peak t =
      3.88) and amygdala (peak t = 4.83), and negative relationships in the ventral
      pallidum (peak t = -3.99) and ventral tegmental area (peak t = -4.03). AN
      participants also exhibited negative relationships between cardiac sensations and
      activation in response to highly palatable foods in the putamen (peak t = -3.41)
      and ventromedial prefrontal cortex (peak t = -3.61). Healthy participants
      exhibited the opposite pattern in all of these regions. CONCLUSIONS: Hedonic and
      interoceptive inferences made by individuals with AN at the sight of food may be
      influenced by atypical visceral interoceptive experience, which could contribute
      to restrictive eating.

PMID- 28498278
TI  - Depression and Survival in a 17-Year Longitudinal Study of People With HIV:
      Moderating Effects of Race and Education.
AB  - OBJECTIVE: The prevalence of clinically significant depressive symptoms is three
      times higher in people living with HIV than in the general population. Although
      studies have shown that depression predicts worse course with HIV, few have
      investigated its relationship with mortality, and none have had a 17-year follow
      up period and been conducted entirely during the time since the advent of
      protease inhibitors. METHODS: We followed a diverse sample of HIV-positive people
      (N = 177) in the mid-range of illness for a study on stress and coping.
      Participants were assessed every 6 months (for 12 years) via blood draw,
      questionnaires, and interview. Depression was measured using the Beck Depression
      Inventory. The study began in March 1997 and mortality was assessed in April
      2014. RESULTS: In the primary analysis depression, analyzed as a continuous
      variable, significantly predicted all-cause mortality (hazard ratio = 1.038, 95%
      confidence interval = 1.008-1.068). With Beck Depression Inventory scores
      dichotomized, the hazard ratio was 2.044 (95% confidence interval = 1.176-3.550).
      Furthermore, this result was moderated by race and educational attainment such
      that depression only predicted worse survival for non-African Americans and those
      with a college education or higher. CONCLUSION: Depression is associated with
      worse long-term survival in people with HIV during 17 years of follow-up.
      Interventions targeting depression may improve well-being and potentially
      survival in individuals with HIV. However, since depression did not predict
      survival in African Americans or those with low education, more research is
      needed to identify risk factors for long term outcomes in these groups.

PMID- 28498279
TI  - Effectiveness of a Stepped, Collaborative, and Coordinated Health Care Network
      for Somatoform Disorders (Sofu-Net): A Controlled Cluster Cohort Study.
AB  - OBJECTIVE: Stepped, collaborative, and coordinated approaches have been proposed
      as the optimal treatment strategy for somatic symptom and related disorders, but
      evidence supporting this strategy is lacking. The aim of this study was to assess
      the effectiveness of a guideline-based health care network for patients who are
      at high risk of somatoform disorder (Sofu-Net). METHODS: In a controlled,
      prospective, observer-blinded cluster cohort study, patients who were at high
      risk of somatoform disorder were recruited at 18 primary care practices in the
      Sofu-Net and at 15 primary care practices that provided care as usual (CAU). The
      primary outcome at 6-month follow-up was the rate at which the patients received
      mental health treatment since the establishment of Sofu-Net. The secondary
      outcomes included the patients' clinical symptom severity. RESULTS: A total of
      119 patients in the Sofu-Net intervention group and 100 patients in the CAU
      control group who were at high risk of somatoform disorder were followed for 6
      months. A significantly greater proportion of Sofu-Net patients than CAU patients
      received mental health treatment (47.9% versus 31.0%; odds ratio = 1.96; 95%
      confidence interval, 1.07-3.58). However, the Sofu-Net group did not show greater
      reductions in clinical symptom burden compared with the CAU group. CONCLUSIONS:
      The treatment of somatoform disorders within a guideline-based health care
      network resulted in increased rates of mental health treatment but failed to
      improve patient clinical outcomes. Future investigations are needed to
      investigate the combined value of health care networks with specialized
      psychotherapy interventions in patients at high risk of somatic symptom and
      related disorders. TRIAL REGISTRATION: ISRCTN55870770.

PMID- 28498280
TI  - Immunohistochemical Characterization of the Origins of Metastatic Well
      differentiated Neuroendocrine Tumors to the Liver.
AB  - Metastatic neoplasms of unknown primary site pose a major challenge to patient
      management. As targeted therapies are now being tailored to neuroendocrine tumors
      (NETs) of different primary sites, identifying the origin of metastatic NETs has
      become increasingly important. Compared with more extensive efforts on metastatic
      adenocarcinomas of unknown primary, the literature on metastatic NETs (often to
      the liver) is relatively sparse and most studies are based on primary tumors. We
      sought to study metastatic well-differentiated NETs to the liver to identify
      markers that predict the site of origin. Eighty-five metastatic NETs to the liver
      were retrieved from the pathology archive. The primary sites were determined
      based on either pathologic review of the primary tumors (in most cases) or
      radiologic/clinical findings. Immunohistochemical labeling for TTF1, CDX2, ISL1,
      NKX2.2, and PDX1 was performed on either tissue microarrays or whole sections.
      The primary sites of the NETs in the study cohort included: pancreas (35%), small
      intestine (32%), rectum (8%), stomach (2%), bile duct (1%), lung (9%), and
      unknown primary (12%). We found predominant expression of TTF1 in lung carcinoid
      (63%), CDX2 in small intestinal (89%) and ISL1 in pancreatic NETs (77%),
      respectively. NKX2.2 was mainly expressed in NETs of the digestive organs. PDX1
      was detected in a small percentage of pancreatic, small intestinal and the single
      bile duct NET. There was no statistically significant association between tumor
      grade (World Health Organization G1 vs. G2) and the expression of any of the
      above markers. The 3-marker panel (TTF1, CDX2, and ISL1) had sensitivities of
      81%, 89%, and 63%, specificities of 100%, 94%, and 100%, positive predictive
      values of 100%, 89%, and 100%, and negative predictive values of 84%, 94%, and
      96% in separating metastatic NETs into 3 major primary sites: pancreas/rectum,
      small intestine, and lung, respectively, with an overall accuracy of 82%.
      Furthermore, this panel predicted a primary site for 6 of the 10 NETs of unknown
      primary, which reduced the NETs of unknown primary from 12% to 5%. Thus, through
      immunohistochemical study of a large series of metastatic NETs to the liver, we
      have demonstrated the utility of a 3-marker panel for the identification of one
      or more potential primary sites of most metastatic NETs, which could provide
      practical guidance in patient management.

PMID- 28498281
TI  - MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast
      Adenoid Cystic Carcinoma than MYB Labeling by FISH.
AB  - Breast adenoid cystic carcinoma (ACC) is a primary breast carcinoma that, like
      salivary gland ACC, displays the t(6;9) translocation resulting in the MYB-NFIB
      gene fusion and immunopositivity for MYB by immunohistochemistry (IHC). However,
      it is not well established whether MYB immunoreactivity or rearrangement can be
      used to support a diagnosis of ACC in a malignant basaloid or benign cribriform
      breast lesion. Whole sections of primary breast ACC (n=11), collagenous
      spherulosis (CS; n=7), and microglandular adenosis (MGA; n=5) and tissue
      microarrays containing 16 basal-like, triple-negative breast carcinomas (TNBC)
      were labeled for MYB by IHC and underwent MYB fluorescence in situ hybridization
      using a break-apart probe. Strong, diffuse nuclear MYB labeling was seen in 100%
      ACC compared with no cases of basal-like TNBC, CS, or MGA (P=0.0001). Any degree
      of nuclear MYB labeling was seen in 100% ACC compared with 54% of all other cases
      (P=0.007), with any labeling seen in 71% CS, 63% basal-like TNBC, and 0% MGA. MYB
      rearrangement was detected in 89% (8/9) of evaluable ACC compared with 4% (1/26)
      of all other evaluable cases (P=0.0001), with a rearrangement detected in 1 (7%;
      n=1/15) evaluable basal-like TNBC. Strong, diffuse nuclear labeling for MYB is
      more sensitive than MYB fluorescence in situ hybridization for breast ACC and can
      be used to support a diagnosis of ACC in a cribriform or basaloid lesion in the
      breast. However, weak and focal labeling should be interpreted with caution as it
      can be seen in other benign cribriform and malignant basaloid lesions.

PMID- 28498282
TI  - Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free
      Survival in Patients With Resected Lung Squamous Cell Carcinoma.
AB  - Tumor spread through air spaces (STAS) is a newly recognized pattern of invasion
      in lung adenocarcinoma. However, clinical significance of STAS has not yet been
      characterized in lung squamous cell carcinoma. In this study, we investigated
      whether STAS could determine clinical outcome in Japanese patients with lung
      squamous cell carcinoma. We reviewed tumor slides from surgically resected lung
      squamous cell carcinomas (n=216). STAS was defined as tumor cells within air
      spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were
      evaluated for histologic subtypes, tumor budding, and nuclear diameter.
      Recurrence-free survival (RFS) was analyzed using the log-rank test and the Cox
      proportional hazards model. Tumor STAS was observed in 87 patients (40%),
      increasing incidence with lymph node metastasis (P=0.037), higher pathologic
      stage (P=0.026), and lymphatic invasion (P=0.033). All cases with STAS showed a
      solid nest pattern. The 5-year RFS for patients with STAS was significantly lower
      than it was for patients without STAS in all patients (P=0.001) and in stage I
      patients (n=134; P=0.041). On multivariate analysis, STAS was an independent
      prognostic factor of a worse RFS (hazard ratio=1.61; P=0.023). Patients with STAS
      had a significantly increased risk of developing locoregional and distant
      recurrences (P=0.012 and 0.001, respectively). We found that tumor STAS was an
      independent predictor of RFS in patients with resected lung squamous cell
      carcinoma, and it was associated with aggressive tumor behavior.

PMID- 28498283
TI  - Synovial Sarcoma of Peripheral Nerves: Analysis of 15 Cases.
AB  - Synovial sarcoma of peripheral nerve (SSPN) is rare with only 26 cases reported
      in English. SSPN is often mistaken for a benign or malignant peripheral nerve
      sheath tumor (PNST) by clinicians and pathologists. Fifteen cases of SSPN were
      retrieved from the pathology files of 3 institutions. All tumors arose in a nerve
      based on imaging and/or operative findings and the diagnoses were histologically
      confirmed. Neuropathic symptoms predominated in 11 women and 4 men, 19- to 62
      year-old (median, 39 years) with tumors involving the ulnar (5), median (3),
      peroneal (3) or sciatic (2) nerve, or the L4 or T1 nerve root (2). Tumor sizes
      ranged from 2 to 13 cm (median, 3.8 cm). The leading clinical diagnosis was PNST
      (9). Treatment was surgical (14) supplemented with radiation therapy (8) and
      chemotherapy (6). Fourteen tumors were monophasic and 1 was biphasic; 4 had
      poorly differentiated (PD) foci (1 rhabdoid). Diagnoses in 12 cases were verified
      by fluorescence in situ hybridization, reverse transcription polymerase chain
      reaction or both methods. Follow-up in 14 patients (median, 32 mo) revealed that
      2/4 patients with PD tumors died with pulmonary metastases; another was alive
      with no current evidence of disease (NED) following 2 local recurrences, while
      the fourth had NED. In contrast, 9/10 patients without PD tumors were alive (7
      NED) and 1 died at 12 months with pulmonary infiltrates. SSPN is under-recognized
      clinically and histologically as it mimics benign and malignant PNST. Molecular
      analysis is recommended to confirm the diagnosis. PD foci, including rhabdoid
      areas, may portend a worse outcome, similar to non-neural-based tumors.

PMID- 28498284
TI  - Undifferentiated and Dedifferentiated Endometrial Carcinomas With POLE
      Exonuclease Domain Mutations Have a Favorable Prognosis.
AB  - POLE exonuclease domain mutations have recently been described in
      undifferentiated endometrial carcinoma but, because of the rarity of this
      aggressive type of endometrial cancer, their prognostic significance is unknown.
      We have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, beta
      catenin, and SMARCB1) and mutational status (POLE, PIK3CA, and PTEN) of 21
      undifferentiated carcinomas (8 undifferentiated and 13 dedifferentiated
      carcinomas). Loss of ARID1A expression was observed in 9 of 19 cases (47%), loss
      of expression of at least 1 DNA mismatch repair protein in 7 (7/21; 33%), and p53
      immunoreaction was aberrant (mutated/inactivated) in 11 cases (11/21; 52%). All
      tumors were negative for beta-catenin. Normal nuclear SMARCB1 (INI1) staining was
      found in all but 1 dedifferentiated case. Two undifferentiated and 7
      dedifferentiated carcinomas showed POLE exonuclease domain mutations (9/21; 42%).
      PIK3CA mutations occurred in six tumors (6/21; 28%) (2 undifferentiated and 4
      dedifferentiated carcinomas). PTEN mutations were found in 7 of 15 cases (47%) (4
      undifferentiated and 3 dedifferentiated carcinomas). POLE-mutated
      undifferentiated and dedifferentiated endometrial carcinomas were more frequently
      stage I tumors than similar carcinomas lacking exonuclease domain mutations (7/9;
      78% vs. 3/12; 25%; P=0.023) and patients had significantly better outcome
      (disease-specific survival) than those without POLE exonuclease domain mutations
      (P=0.02). Determination of the POLE mutation status is important for the
      management of these patients.

PMID- 28498285
TI  - C-MYC and Its Main Ubiquitin Ligase, FBXW7, Influence Cell Proliferation and
      Prognosis in Adult T-cell Leukemia/Lymphoma.
AB  - Smoldering-type and chronic-type adult T-cell leukemia/lymphomas (ATLL) patients
      have relatively indolent clinical courses, but often progress into aggressive
      lymphoma-type and acute-type disease. We examined the roles of transcription
      factor C-MYC and its ubiquitin ligase FBXW7 in tumor tissues from 137 patients
      with ATLL. Immunohistochemical tests showed >=50% of lymphoma cells in 78.7%
      (48/61) of lymphoma-type, and 64.9% (24/37) of acute-type samples expressed C
      MYC, significantly higher than was seen in smoldering-type (3.6%) and chronic
      type (9.1%) samples (P<0.01). Real-time polymerase chain reaction showed C-MYC
      mRNA expression in lymphoma-type and acute-type samples were significantly higher
      than in smoldering-type (P<0.01). C-MYC expression was highly correlated with its
      mRNA levels (rho=0.65, P<0.0001), chromosomal amplification and duplication
      (rho=0.3, P=0.045) and MIB1 labeling index (rho=0.69, P<0.0001). Expression of
      FBXW7 protein and mRNA in lymphoma-type samples were significantly lower than
      those of smoldering-type (P<0.01 for each), and both were inversely correlated
      with C-MYC (protein: rho=-0.4, P=0.0002; mRNA: rho=-0.31, P=0.015). Seven
      patients with smoldering-type or chronic-type ATLL converted to acute-type, in 4
      of whom C-MYC expression increased from <50% to >=50%. Patients with >=50% C-MYC
      or MIB1 had significantly worse prognosis than those with <50% C-MYC (P=0.0004)
      or MIB1 (P<0.0001), as did those with >=7.5 C-MYC mRNA scores (P=0.033); whereas
      significantly better prognosis was associated with >=50% FBXW7 protein (P=0.0006)
      or >=0.17 FBXW7 mRNA (P=0.016). C-MYC and FBXW7 affect ATLL proliferation and
      progression, and low FBXW7 may increase C-MYC expression. C-MYC was a critical
      prognostic factor in ATLL patients.

PMID- 28498286
TI  - Biphasic Squamoid Alveolar Renal Cell Carcinoma: 2 Cases in a Family Supporting a
      Continuous Spectrum With Papillary Type I Renal Cell Carcinoma.

PMID- 28498287
TI  - Molecular Profiling Reveals a Clonal Relationship Between Ovarian Mucinous Tumors
      and Corresponding Mural Carcinomatous Nodules.
AB  - Benign or malignant mural nodules rarely occur in mucinous tumors (MTs) of the
      ovary and malignant nodules can show mesenchymal or epithelial differentiation.
      The histogenesis of mural nodules is unclear and it has been suggested that these
      may evolve through divergent differentiation of the mucinous neoplasm or
      alternatively represent a collision phenomenon. To test these possibilities we
      compared the molecular profile of 7 ovarian MTs with their matched mural
      carcinomatous nodules (MCNs) by next-generation sequencing. We found identical
      KRAS mutations in paired MTs and MCNs in 6 cases, one of which also showed
      identical CDH1 mutations in both components. In 1 tumor a KRAS mutation was
      detected in the mucinous neoplasm but not in the MCN; however, identical p53
      mutations were present in both tumor elements. Unpaired p53 and PTEN mutations
      were detected only in the MCN in 2 cases, while mutations in p53 and PIK3CA genes
      were observed only in the MT in 2 cases. The overall comparative genomic profile
      was consistent with the neoplastic nature of the MCNs and strongly supported
      their clonal relationship with the more differentiated mucinous neoplasms. MCNs
      possibly develop through the acquisition of additional genomic alterations, such
      as p53 and PTEN mutations, resulting in an anaplastic morphologic phenotype. Our
      findings also suggest that ovarian MTs with MCNs often arise in KRAS mutant
      neoplasms. However, mutations in other genes such as PIK3CA and CDH1 may play a
      role in the neoplastic evolution of a subset of these tumors.

PMID- 28498289
TI  - Incidence of Cancer in Spinal Deformity Patients Receiving High-Dose (>=40 mg)
      Bone Morphogenetic Protein (rhBMP-2).
AB  - STUDY DESIGN: Level III, Retrospective observational study. OBJECTIVE: To
      determine if there is an increased risk of developing cancer after exposure to
      high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) and if risk is
      dose and/or exposure-dependent. SUMMARY OF BACKGROUND DATA: Concerns have been
      raised regarding a relationship between rhBMP-2 and cancer. METHODS: A total of
      642 adult deformity patients from a single institution receiving a cumulative
      rhBMP-2 dose >=40 mg from July, 2002 to July, 2009 were identified. Patients with
      a history of surveillance, epidemiology, and end result (SEER) cancer before
      rhBMP-2 exposure were excluded. To determine the occurrence of a cancer event,
      questionnaires were mailed and telephone follow up attempted for nonresponders.
      Only cancers tracked by the National Cancer Institute (NCI) SEER registry were
      included. Observed cancer counts were compared to expected cancer counts based on
      general population incidence rates within 5-year age strata. Cumulative incidence
      competing risk (CICR) modeling was used to evaluate the association between rhBMP
      2 exposure and cancer controlling for potential confounding variables. RESULTS:
      Forty-nine patients were lost-to-follow up, leaving 593 patients (92.4%; 138
      males/455 females) available for analysis. Mean age was 52.8 years at the time of
      first exposure. Mean cumulative rhBMP-2 dose was 113.5 mg with 85% having one
      exposure (range: 1-8). Mean follow-up [date of exposure to date of death
      (regardless of cause) or returned completed questionnaire] was 5.6 +/- 1.9 years;
      median follow up was 5.4 years. A total of 342 patients have greater than 5-year
      follow up. Minimum follow up was 2.0 years or until occurrence of a SEER cancer.
      Our total 8-year cumulative incidence of new SEER cancer accounting for the
      competing risk of death was 7.4% for 30 cancers in 593 patients. Fewer cancers
      were observed than expected based on general population rates, though the
      difference was not statistically significant (expected = 34; standardized
      incidence ratio = 0.88, 95% confidence interval, CI = 0.60-1.26). CICR found
      neither cumulative rhBMP-2 dose (hazard ratio, HR = 0.995, 95% CI 0.988-1.003; P
      = 0.249) nor number of exposures (HR = 0.776, 95% CI 0.359-1.677; P = 0.519)
      increased the risk of developing a postexposure cancer after controlling for
      known cancer risk factors. CONCLUSION: The incidence of a SEER cancer after rhBMP
      2 exposure was similar to incidence reported by the NCI. There were no
      significant rhBMP-2 dose or multi-exposure related risks of developing a life
      threatening cancer. LEVEL OF EVIDENCE: 3.

PMID- 28498290
TI  - The Relationship Between MRI Signal Intensity Changes, Clinical Presentation, and
      Surgical Outcome in Degenerative Cervical Myelopathy: Analysis of a Global
      Cohort.
AB  - STUDY DESIGN: Retrospective analysis of prospective data. OBJECTIVE: To assess
      the relationship between MRI signal intensity changes, clinical presentation, and
      surgical outcome in degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND
      DATA: Several studies have sought to assess the extent of spinal cord dysfunction
      and the potential for postoperative neurological recovery through the evaluation
      of spinal cord signal change on T2-weighted (T2WI) and T1-weighted images (T1WI).
      There remains ambiguity if T2WI and T1WI signal changes (1) relate to baseline
      severity, and (2) predict neurological recovery after surgical treatment.
      METHODS: Four hundred nineteen MRIs from two prospective multicenter studies were
      examined. Images were assessed for the presence, levels, and location of spinal
      cord signal intensity changes and compared with clinical data. Signal changes
      were also evaluated for the prediction of 2-year postoperative outcome using mJOA
      parameters. RESULTS: MRIs were categorized by T1WI and T2WI signal change: no
      signal change (28.9%), T2WI hyperintensity-only (T2WI-only, 51.8%), and T2WI
      hyperintensity and T1WI-hypointensity (T1WI+T2WI, 19.3%). T2WI-hyperintensity was
      present at multiple levels in 27% of patients overall. Baseline severity
      increased from no signal change to T2WI-only to T2WI+T1WI (P < 0.0001), and there
      was an incremental increase in the frequency of signs/symptoms. There were no
      differences in outcomes between no signal change and T2WI-only groups. The
      presence of T1WI-hypointensity correlated with reduced recovery ratio (P = 0.03)
      and likelihood of an optimal surgical outcome (P = 0.005), adjusting for baseline
      mJOA. A greater number of T2WI-hyperintensity levels was also associated with
      worse baseline severity (P < 0.0001) and recovery ratio (P = 0.001). CONCLUSION:
      This analysis of a global cohort of DCM patients shows a stepwise trend toward
      increasing impairment from no signal change to T2WI-hypertensity to T1WI
      hypointensity. T1WI signal change indicates more permanent injury, portending
      decreased functional recovery. T2WI-hyperintensity alone does not predict
      outcomes. Multiple levels of T2WI-hyperintensity suggest additional tissue
      injury, correlating with worse clinical impairment and recovery potential. LEVEL
      OF EVIDENCE: 2.

PMID- 28498291
TI  - Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic
      Papillary Thyroid Carcinoma.
AB  - : MINI: A 3D printing technology is proposed for reconstructing multilevel
      cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma.
      The personalized porous implant printed in Ti6AL4V provided excellent
      physicochemical properties and biological performance, including
      biocompatibility, osteogenic activity, and bone ingrowth effect. STUDY DESIGN: A
      unique case report. OBJECTIVE: A three-dimensional (3D) printing technology is
      proposed for reconstructing multilevel cervical spine (C2-C4) after resection of
      metastatic papillary thyroid carcinoma in a middle-age female patient. SUMMARY OF
      BACKGROUND DATA: Papillary thyroid carcinoma is a malignant neoplasm with a
      relatively favorable prognosis. A metastatic lesion in multilevel cervical spine
      (C2-C4) destroys neurological functions and causes local instability. Radical
      excision of the metastasis and reconstruction of the cervical vertebrae sequence
      conforms with therapeutic principles, whereas the special-shaped multilevel upper
      cervical spine requires personalized implants. 3D printing is an additive
      manufacturing technology that produces personalized products by accurately
      layering material under digital model control via a computer. Reporting of this
      recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in
      the literature. METHODS: Anterior-posterior surgery was performed in one stage.
      Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with
      insertion of a personalized implant manufactured by 3D printing technology, were
      performed to rebuild the cervical spine sequences. The porous implant was printed
      in Ti6AL4V with perfect physicochemical properties and biological performance,
      such as biocompatibility and osteogenic activity. Finally, lateral mass screw
      fixation was performed via a posterior approach. RESULTS: Patient neurological
      function gradually improved after the surgery. The patient received 11/17 on the
      Japanese Orthopedic Association scale and ambulated with a personalized skull
      neck-thorax orthosis on postoperative day 11. She received radioiodine I therapy.
      The plane x-rays and computed tomography revealed no implant displacement or
      subsidence at the 12-month follow-up mark. CONCLUSION: The presented case
      substantiates the use of 3D printing technology, which enables the
      personalization of products to solve unconventional problems in spinal surgery.
      LEVEL OF EVIDENCE: 5.

PMID- 28498292
TI  - Effects of Conflicts of Interest on Practice Patterns and Complication Rates in
      Spine Surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We sought to determine
      whether financial relationships with industry had any impact on operative and/or
      complication rates of spine surgeons performing fusion surgeries. SUMMARY OF
      BACKGROUND DATA: Recent actions from Congress and the Institute of Medicine have
      highlighted the importance of conflicts of interest among physicians. Orthopedic
      surgeons and neurosurgeons have been identified as receiving the highest amount
      of industry payments among all specialties. No study has yet investigated the
      potential effects of disclosed industry payments with quality and choices of
      patient care. METHODS: A comprehensive database of spine surgeons in the United
      States with compiled data of industry payments, operative fusion rates, and
      complication rates was created. Practice pattern data were derived from a
      publicly available Medicare-based database generated from selected CPT codes from
      2011 to 2012. Complication rate data from 2009 to 2013 were extracted from the
      ProPublica-Surgeon-Scorecard database, which utilizes postoperative inhospital
      mortality and 30-day-readmission for designated conditions as complications of
      surgery. Data regarding industry payments from 2013 to 2014 were derived from the
      Open Payments website. Surgeons performing <10 fusions, those without
      complication data, and those whose identity could not be verified through public
      records were excluded. Pearson correlation coefficients and multivariate
      regression analyses were used to determine the relationship between industry
      payments, operative fusion rate, and/or complication rate. RESULTS: A total of
      2110 surgeons met the inclusion criteria for our database. The average operative
      fusion rate was 8.8% (SD 4.8%), whereas the average complication rate for lumbar
      and cervical fusion was 4.1% and 1.9%, respectively. Pearson correlation analysis
      revealed a statistically significant but negligible relationship between
      disclosed payments/transactions and both operative fusion and complication rates.
      CONCLUSION: Our findings do not support a strong correlation between the payments
      a surgeon receives from industry and their decisions to perform spine fusion or
      associated complication rates. Large variability in the rate of fusions performed
      suggests a poor consensus for indications for spine fusion surgery. LEVEL OF
      EVIDENCE: 3.

PMID- 28498293
TI  - What Is the Actual 3D Representation of the Rib Vertebra Angle Difference (Mehta
      Angle)?
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To establish the relevance of the
      conventional two-dimensional (2D) rib vertebra angle difference (RVAD) and the
      relationship with the complex three-dimensional (3D) apical morphology in
      scoliosis. SUMMARY OF BACKGROUND DATA: The RVAD, also known as Mehta angle,
      describes apical rib asymmetry on conventional radiographs and was introduced as
      a prognostic factor for curve severity in early onset scoliosis, and later
      applied to other types of scoliosis as well. METHODS: An existing idiopathic
      scoliosis database of high-resolution computed tomography scans used in previous
      work, acquired for spinal navigation, was used. Eighty-eight patients (Cobb angle
      46 degrees -109 degrees ) were included. Cobb angle and 2D RVAD, as described by
      Mehta, were measured on the conventional radiographs and coronal digitally
      reconstructed radiographs (DRR) of the prone computed tomography scans. A
      previously validated, semiautomatic image processing technique was used to
      acquire complete 3D spinal reconstructions for the measurement of the 3D RVAD in
      a reconstructed true coronal plane, axial rotation, and sagittal morphology.
      RESULTS: The 2D RVAD on the x-ray was on average 25.3 degrees  +/- 11.0 degrees 
      and 25.6 degrees  +/- 12.8 degrees  on the DRR (P = 0.990), but in the true 3D
      coronal view of the apex, hardly any asymmetry remained (3D RVAD: 3.1 degrees  +/
      12.5 degrees ; 2D RVAD on x-ray and DRR vs. 3D RVAD: P < 0.001). 2D apical rib
      asymmetry in the anatomical coronal plane did not correlate with the same RVAD
      measurements in the 3D reconstructed coronal plane of the rotated apex (r =
      0.155; P = 0.149). A larger 2D RVAD was found to correlate linearly with
      increased axial rotation (r = 0.542; P < 0.001) and apical lordosis (r = 0.522; P
      < 0.001). CONCLUSION: The 2D RVAD represents a projection-based composite
      radiographic index reflecting the severity of the complex 3D apical morphology
      including axial rotation and apical lordosis. It indicates a difference in
      severity of the apical deformation. LEVEL OF EVIDENCE: 4.

PMID- 28498294
TI  - Target Serum Sodium Levels During Intensive Care Unit Management of Aneurysmal
      Subarachnoid Hemorrhage.
AB  - INTRODUCTION: Dysnatremia commonly occur in the intensive care unit (ICU)
      management of patients with aneurysmal subarachnoid hemorrhage (SAH). However,
      detailed management strategies have not been provided even by current guidelines.
      The purposes of this study were to examine the association of abnormal serum
      sodium levels with unfavorable neurologic outcomes and to identify the target
      range of serum sodium in patients with SAH. METHODS: We retrospectively reviewed
      all patients who were consecutively hospitalized with a confirmed diagnosis of
      SAH between January 2009 and December 2015. Univariate/multivariate analyses were
      performed to identify the independent predictors of an unfavorable neurologic
      outcome (modified Rankin scale of 3-6 upon hospital discharge). RESULTS: There
      were 131 patients included in this study. Unfavorable neurologic outcomes
      occurred in 45% of patients. On multiple regression analysis, age, Hunt and
      Kosnik grade, and serum sodium levels in the ICU at the maximum [odds ratio (OR),
      1.18; 95% CI, 1.05-1.35; P < 0.01] and minimum (OR, 0.88; 95% CI, 0.77-0.99; P =
      0.048) values were significantly associated with unfavorable neurologic outcomes.
      The receiver operating characteristic curve analysis showed that the cut-off
      serum sodium levels were 145 mmol/L for maximum value and 132 mmol/L for minimum
      value. Patients with hyponatremia and hypernatremia during the first 2 weeks in
      the ICU accounted for 88.2% of patients with an unfavorable neurologic outcome;
      whereas, those with normal sodium levels accounted for only 15.6%. CONCLUSIONS:
      In patients with SAH, both hyponatremia and hypernatremia during ICU management
      were significantly associated with unfavorable neurologic outcomes.

PMID- 28498295
TI  - Epidemiology of Anaphylactic Shock and its Related Mortality in Hospital Patients
      in Taiwan: A Nationwide Population-Based Study.
AB  - Anaphylactic shock is potentially life-threatening. However, there is a paucity
      of data about its incidence and associated mortality, particularly in Asian
      populations. We aimed to investigate the epidemiology of anaphylactic shock and
      its related mortality after the hospitalization of patients in the general
      population of Taiwan. The National Health Insurance Research Database was used to
      identify patients with anaphylactic shock and estimate its incidence for
      inpatients sampled from 2005 to 2012. The pattern of anaphylactic shock and
      anaphylactic shock-related mortality rate was also examined. Of 22,080,199
      patients who were admitted to hospitals from 2005 to 2012, there were 2,289
      incident cases of anaphylactic shock and 2,219 people were included. Incidence of
      hospitalizations due to anaphylactic shock ranged from 12.71 to 13.23 per million
      of the population between 2005 and 2012. The incidence of anaphylactic shock in
      our study was substantially lower than other western countries, including the
      United States. There were 24 deaths due to drug-induced anaphylactic shock among
      the hospitalizations; overall mortality rate was 1.08%. Eighteen (0.81%) patients
      died within 30 days; 22 (0.99%) died within 2 months following the anaphylactic
      shock. The highest incidence occurred in patients aged 70-79 years. Conversely,
      food-induced anaphylactic shock was not influenced by age. In conclusion, drug
      induced anaphylactic shock was a major cause of death due to anaphylactic shock
      in hospitalized patients. Most cases of anaphylactic shock occurred in the older
      population, and the mortality rate was lower in females than in males, though the
      difference was not significant.

PMID- 28498296
TI  - Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier
      Regeneration Following Acute Injury.
AB  - Intestine barrier disruption and bacterial translocation can contribute to sepsis
      and multiple organ failure, leading causes of mortality in burn-injured patients.
      In addition, findings suggest that ethanol (alcohol) intoxication at the time of
      injury worsens symptoms associated with burn injury. We have previously shown
      that interleukin-22 (IL-22) protects from intestinal leakiness and prevents
      overgrowth of gram-negative bacteria following ethanol and burn injury, but how
      IL-22 mediates these effects has not been established. Here, utilizing a mouse
      model of ethanol and burn injury, we show that the combined insult results in a
      significant loss of proliferating cells within small intestine crypts and
      increases Enterobacteriaceae copies, despite elevated levels of the antimicrobial
      peptide lipocalin-2. IL-22 administration restored numbers of proliferating cells
      within crypts, significantly increased Reg3beta, Reg3gamma, lipocalin-2 AMP
      transcript levels in intestine epithelial cells, and resulted in complete
      reduction of Enterobacteriaceae in the small intestine. Knockout of signal
      transducer and activator of transcription factor-3 (STAT3) in intestine
      epithelial cells resulted in complete loss of IL-22 protection, demonstrating
      that STAT3 is required for intestine barrier protection following ethanol
      combined with injury. Together, these findings suggest that IL-22/STAT3 signaling
      is critical to gut barrier integrity and targeting this pathway may be of
      beneficial clinical relevance following burn injury.

PMID- 28498297
TI  - Gastrointestinal Colonization of Candida Albicans Increases Serum (1->3)-beta-D
      Glucan, without Candidemia, and Worsens Cecal Ligation and Puncture Sepsis in
      Murine Model.
AB  - The role of intestinal Candida albicans in bacterial sepsis, in the absence of
      candidemia, was investigated in murine models. Live C albicans or normal saline
      solution (NSS) was administered orally once, followed by 5 days of daily oral
      antibiotic-mixtures (ATB). Cecal ligation and puncture (CLP) was then performed
      to induce sepsis.Fecal Candida was detected by culture only in models with
      Candida administration. Oral Candida administration with/without ATB enhanced gut
      pathogenic bacteria as determined by microbiome analysis. Despite negative
      candidemia, serum (1->3)-beta-D-glucan (BG) was higher in CLP with Candida
      preconditioning models than in CLP-controls (NSS-preconditioning) at 6 and/or 18
      h post-CLP. Blood bacterial burdens were not increased with Candida
      administration.Additionally, CLP with high-dose Candida (10 colony forming units)
      induced higher levels of fecal Candida, serum BG, serum IL-6, and mortality than
      the lowest dose (100 colony forming units). Interestingly, fluconazole attenuated
      fecal Candida and improved survival in mice with live-Candida administration, but
      not in the CLP-controls. Heat-killed Candida preparations or their supernatants
      reduced bone marrow-derived macrophage killing activity in vitro but enhanced
      cytokine production.In conclusion, intestinal abundance of fungi and/or fungal
      molecules was associated with increased bacterial sepsis severity, perhaps
      through cytokine storm induction and/or decreased macrophage killing activity.
      These observations suggest that further investigation of the potential role of
      intestinal fungal burdens in sepsis is warranted.

PMID- 28498298
TI  - Hydrogen Sulfide: A Potential Novel Therapy for the Treatment of Ischemia.
AB  - Hydrogen sulfide (H2S) is a novel signaling molecule most recently found to be of
      fundamental importance in cellular function as a regulator of apoptosis,
      inflammation, and perfusion. Mechanisms of endogenous H2S signaling are poorly
      understood; however, signal transmission is thought to occur via persulfidation
      at reactive cysteine residues on proteins. Although much has been discovered
      about how H2S is synthesized in the body, less is known about how it is
      metabolized. Recent studies have discovered a multitude of different targets for
      H2S therapy, including those related to protein modification, intracellular
      signaling, and ion channel depolarization. The most difficult part of studying
      hydrogen sulfide has been finding a way to accurately and reproducibly measure
      it. The purpose of this review is to: elaborate on the biosynthesis and
      catabolism of H2S in the human body, review current knowledge of the mechanisms
      of action of this gas in relation to ischemic injury, define strategies for
      physiological measurement of H2S in biological systems, and review potential
      novel therapies that use H2S for treatment.

PMID- 28498299
TI  - Machine Learning for Predicting Outcomes in Trauma.
AB  - To date, there are no reviews on machine learning (ML) for predicting outcomes in
      trauma. Consequently, it remains unclear as to how ML-based prediction models
      compare in the triage and assessment of trauma patients. The objective of this
      review was to survey and identify studies involving ML for predicting outcomes in
      trauma, with the hypothesis that models predicting similar outcomes may share
      common features but the performance of ML in these studies will differ greatly.
      MEDLINE and other databases were searched for studies involving trauma and ML.
      Sixty-five observational studies involving ML for the prediction of trauma
      outcomes met inclusion criteria. In total 2,433,180 patients were included in the
      studies. The studies focused on prediction of the following outcome measures:
      survival/mortality (n = 34), morbidity/shock/hemorrhage (n = 12), hospital length
      of stay (n = 7), hospital admission/triage (n = 6), traumatic brain injury (n =
      4), life-saving interventions (n = 5), post-traumatic stress disorder (n = 4),
      and transfusion (n = 1). Six studies were prospective observational studies. Of
      the 65 studies, 33 used artificial neural networks for prediction. Importantly,
      most studies demonstrated the benefits of ML models. However, algorithm
      performance was assessed differently by different authors. Sensitivity
      specificity gap values varied greatly from 0.035 to 0.927. Notably, studies
      shared many features for model development. A common ML feature base may be
      determined for predicting outcomes in trauma. However, the impact of ML will
      require further validation in prospective observational studies and randomized
      clinical trials, establishment of common performance criteria, and high-quality
      evidence about clinical and economic impacts before ML can be widely accepted in
      practice.

PMID- 28498300
TI  - Volatile Decay Products in Breath During Peritonitis Shock are Attenuated by
      Enteral Blockade of Pancreatic Digestive Proteases.
AB  - There is a need to develop markers for early detection of organ failure in shock
      that can be noninvasively measured at point of care. We explore here the use of
      volatile organic compounds (VOCs) in expired air in a rat peritonitis shock
      model. Expired breath samples were collected into Tedlar gas bags and analyzed by
      standardized gas chromatography. The gas chromatograms were digitally analyzed
      for presence of peak amounts over a range of Kovach indices. Following the
      induction of peritonitis, selected volatile compounds were detected within about
      1 h, which remained at elevated amounts over a 6 h observation period. These VOCs
      were not present in control animals without peritonitis. Comparisons with know
      VOCs indicate that they include 1,4-diaminobutane and trimethylamine N-oxide.
      When pancreatic digestive proteases were blocked with tranexamic acid in the
      intestine and peritoneum, a procedure that serves to reduce organ failure in
      shock, the amounts of VOCs in the breath decreased spontaneously to control
      values without peritonitis. These results indicate that peritonitis shock is
      accompanied by development of volatile organic compounds that may be generated by
      digestive enzymes in the small intestine. VOCs may serve as indicators for
      detection of early forms of autodigestion by digestive proteases.

PMID- 28498301
TI  - Seroprevalence of Hepatitis A Twelve Years After the Implementation of Toddlers'
      Vaccination: A Population-Based Study in Israel.
AB  - BACKGROUND: In 1999, Israel became the first country to introduce an inactivated
      hepatitis A vaccine into its national childhood vaccination program. The
      objective of the present study was to evaluate the seroprevalence of hepatitis A
      virus antibodies in the Israeli population before and after the introduction of
      the program. METHODS: A cross-sectional serosurvey using the National Serum Bank
      was conducted on 1883 and 2027 serum samples collected before and after
      introduction of the vaccine, respectively. Serologic tests for the presence of
      hepatitis A IgG antibodies were performed using an automated enzyme-linked
      fluorescent assay. RESULTS: The age-adjusted seroprevalence rates of hepatitis A
      virus antibodies before implementation of hepatitis A vaccination program were
      47.1% [95% confidence interval (CI): 44.7%-49.5%] among Jews and 82.8% (95% CI:
      79.6%-85.9%) among Arabs, increasing 12 years after to 67.4% (95% CI: 64.7%
      70.0%) and 88.2% (95% CI: 86.1%-90.2%), respectively. CONCLUSIONS: The
      seropositivity rate among Jews and Arabs increased significantly among the
      cohorts included in the program. However, among Jews, a significant increase in
      seropositivity was also detected among age groups not included in the vaccination
      program. The decrease in the incidence of hepatitis A in Israel is a consequence
      of high vaccine uptake, persistent seropositivity rates after vaccination and the
      considerable number of people vaccinated beyond the program.

PMID- 28498302
TI  - Reaction of the BCG Scar in the Acute Phase of Kawasaki Disease in Mexican
      Children.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute self-limited systemic vasculitis
      that primarily affects children <5 years old. There is no specific diagnostic
      test. A reaction at the Bacille Calmette-Guerin (BCG) inoculation site has been
      reported as a common finding in patients with KD where BCG vaccination is
      mandatory. The purpose of this study was to evaluate the frequency of
      reactivation of the BCG in Mexican children diagnosed with KD. METHODS: A
      retrospective study of all patients diagnosed with KD from August 1, 1995, to
      August 31, 2015, at our Institution was performed. The clinical profile,
      laboratory results, treatment used and coronary artery abnormalities in the BCG
      reactive and the BCG nonreactive groups were analyzed and compared. RESULTS: We
      included 399 patients with KD. Ninety-seven (24.3%) had BCG reaction at the
      inoculation site. The BCG(+) group was younger than the BCG(-) group (P < 0.000).
      There were 18 (18.55%) incomplete cases in the BCG(+) group compared with 65
      (21.52%) in the BCG(-) group without statistical significance. The BCG+ group
      developed coronary artery aneurysms in 37 cases and the BCG(-) group developed
      coronary artery aneurysms in 111 cases without statistical significance.
      Multivariate analysis showed that younger age at diagnosis was the only variable
      associated with a reaction at the BCG inoculation site in patients with KD.
      CONCLUSIONS: In Mexico, a country with a National BCG Vaccination Program and a
      low incidence of KD, reaction at the BCG inoculation site could be a useful
      diagnostic sign of KD.

PMID- 28498303
TI  - Varicella Zoster Virus-Associated Necrotizing Retinitis After Chickenpox in a 10
      Year-Old Female: A Case Report.
AB  - A necrotizing retinitis in children is a rare but vision-threatening ocular
      complication of chickenpox. We report a 10-year-old girl who developed chickenpox
      1 month before presenting with panuveitis and necrotizing retinitis. After prompt
      antiviral treatment, her inflammatory signs were resolved. Early detection and
      treatment of varicella zoster-associated necrotizing retinitis after chickenpox
      can achieve good visual outcome.

PMID- 28498304
TI  - Pharmaceutical Dosing Errors at a Pediatric HIV Clinic in Mwanza, Tanzania.
AB  - The outpatient medication dosing error rate at a pediatric HIV clinic in Mwanza,
      Tanzania, was about 1 in every 34 prescriptions. Young children were at highest
      risk of a dosing error likely because of dose changes with growth and also the
      inconsistent supply of pediatric formulations. Majority of errors occurred at
      consecutive visits suggesting clinicians reordered medication without double
      checking dosing.

PMID- 28498305
TI  - Aminoglycosides Monotherapy as First-Line Treatment for Febrile Urinary Tract
      Infection in Children.
AB  - We report a retrospective monocentric descriptive study performed in CHI Creteil
      for 20 months to describe the management and outcome of amikacin monotherapy as
      an alternative to third-generation cephalosporins for empiric treatment of
      febrile urinary tract infection (FUTI) in children. Data were analyzed for 151
      children, and 90 selected cases were classified as certain or highly probable
      FUTI. Escherichia coli infection was found in 89 cases. In all patients, fever
      was resolved within 72 hours after beginning amikacin treatment. Only 5.3% of
      children were febrile after 48 hours. The mean amikacin treatment duration was
      3.05 +/- 0.13 days before oral treatment began (guided by antibiotic
      susceptibility testing). Amikacin monotherapy seems effective for the initial
      management of FUTI in children.

PMID- 28498307
TI  - An Improved Design of the Spiral-Coil EMAT for Enhancing the Signal Amplitude.
AB  - The low energy transition efficiency of electromagnetic ultrasonic transducer
      (EMAT) is a common problem in practical application. For the purpose of enhancing
      the amplitude of the received signal, an improved double-coil bulk wave EMAT is
      proposed for the thickness measurement of metallic block. This new configuration
      of magnets consists of a solid cylindrical magnet and a ring-shaped magnet
      encircling the outer side of the solid cylindrical one. A double-coil was applied
      instead of a single spiral-coil. Numerical simulations were performed to analyze
      and optimize the proposed configuration of the EMAT by the 2-D axisymmetric
      finite element model (FEM). The experiment effectively verifies the rationality
      of the new configuration and the feasibility of improving the signal strength.

PMID- 28498306
TI  - A Conserved Residue, Tyrosine (Y) 84, in H5N1 Influenza A Virus NS1 Regulates IFN
      Signaling Responses to Enhance Viral Infection.
AB  - The non-structural protein, NS1, is a virulence factor encoded by influenza A
      viruses (IAVs). In this report, we provide evidence that the conserved residue,
      tyrosine (Y) 84, in a conserved putative SH2-binding domain in
      A/Duck/Hubei/2004/L-1 [H5N1] NS1 is critical for limiting an interferon (IFN)
      response to infection. A phenylalanine (F) substitution of this Y84 residue
      abolishes NS1-mediated downregulation of IFN-inducible STAT phosphorylation, and
      surface IFNAR1 expression. Recombinant IAV (rIAV) [H1N1] expressing A/Grey
      Heron/Hong Kong/837/2004 [H5N1] NS1-Y84F (rWSN-GH-NS1-Y84F) replicates to lower
      titers in human lung epithelial cells and is more susceptible to the antiviral
      effects of IFN-beta treatment compared with rIAV expressing the intact H5N1 NS1
      (rWSN-GH-NS1-wt). Cells infected with rWSN-GH-NS1-Y84F express higher levels of
      IFN stimulated genes (ISGs) associated with an antiviral response compared with
      cells infected with rWSN-GH-NS1-wt. In mice, intranasal infection with rWSN-GH
      NS1-Y84F resulted in a delay in onset of weight loss, reduced lung pathology,
      lower lung viral titers and higher ISG expression, compared with mice infected
      with rWSN-GH-NS1-wt. IFN-beta treatment of mice infected with rWSN-GH-NS1-Y84F
      reduced lung viral titers and increased lung ISG expression, but did not alter
      viral titers and ISG expression in mice infected with rWSN-GH-NS1-wt. Viewed
      altogether, these data suggest that the virulence associated with this conserved
      Y84 residue in NS1 is, in part, due to its role in regulating the host IFN
      response.

PMID- 28498308
TI  - Metal-Organic Frameworks as Active Materials in Electronic Sensor Devices.
AB  - In the past decade, advances in electrically conductive metal-organic frameworks
      (MOFs) and MOF-based electronic devices have created new opportunities for the
      development of next-generation sensors. Here we review this rapidly-growing
      field, with a focus on the different types of device configurations that have
      allowed for the use of MOFs as active components of electronic sensor devices.

PMID- 28498309
TI  - Effective Social Relationship Measurement and Cluster Based Routing in Mobile
      Opportunistic Networks.
AB  - In mobile opportunistic networks, the social relationship among nodes has an
      important impact on data transmission efficiency. Motivated by the strong share
      ability of "circles of friends" in communication networks such as Facebook,
      Twitter, Wechat and so on, we take a real-life example to show that social
      relationships among nodes consist of explicit and implicit parts. The explicit
      part comes from direct contact among nodes, and the implicit part can be measured
      through the "circles of friends". We present the definitions of explicit and
      implicit social relationships between two nodes, adaptive weights of explicit and
      implicit parts are given according to the contact feature of nodes, and the
      distributed mechanism is designed to construct the "circles of friends" of nodes,
      which is used for the calculation of the implicit part of social relationship
      between nodes. Based on effective measurement of social relationships, we propose
      a social-based clustering and routing scheme, in which each node selects the
      nodes with close social relationships to form a local cluster, and the self
      control method is used to keep all cluster members always having close
      relationships with each other. A cluster-based message forwarding mechanism is
      designed for opportunistic routing, in which each node only forwards the copy of
      the message to nodes with the destination node as a member of the local cluster.
      Simulation results show that the proposed social-based clustering and routing
      outperforms the other classic routing algorithms.

PMID- 28498310
TI  - Selective Expression of Flt3 within the Mouse Hematopoietic Stem Cell
      Compartment.
AB  - The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is
      expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating
      mutations are commonly present in acute myeloid and lymphoid leukemias. These
      findings underscore the importance of Flt3 to steady-state and malignant
      hematopoiesis. In this study, the expression of Flt3 protein and Flt3 mRNA by
      single cells within the hematopoietic stem cell (HSC) and HPC bone marrow
      compartments of C57/BL6 mice was investigated using flow cytometry and the
      quantitative reverse transcription polymerase chain reaction. Flt3 was
      heterogeneously expressed by almost all of the populations studied, including
      long-term reconstituting HSC and short-term reconstituting HSC. The
      erythropoietin receptor (EpoR) and macrophage colony-stimulating factor receptor
      (M-CSFR) were also found to be heterogeneously expressed within the multipotent
      cell compartments. Co-expression of the mRNAs encoding Flt3 and EpoR rarely
      occurred within these compartments. Expression of both Flt3 and M-CSFR protein at
      the surface of single cells was more commonly observed. These results emphasize
      the heterogeneous nature of HSC and HPC and the new sub-populations identified
      are important to understanding the origin and heterogeneity of the acute myeloid
      leukemias.

PMID- 28498312
TI  - A Formal Approach to the Selection by Minimum Error and Pattern Method for Sensor
      Data Loss Reduction in Unstable Wireless Sensor Network Communications.
AB  - There are wireless networks in which typically communications are unsafe. Most
      terrestrial wireless sensor networks belong to this category of networks. Another
      example of an unsafe communication network is an underwater acoustic sensor
      network (UWASN). In UWASNs in particular, communication failures occur frequently
      and the failure durations can range from seconds up to a few hours, days, or even
      weeks. These communication failures can cause data losses significant enough to
      seriously damage human life or property, depending on their application areas. In
      this paper, we propose a framework to reduce sensor data loss during
      communication failures and we present a formal approach to the Selection by
      Minimum Error and Pattern (SMEP) method that plays the most important role for
      the reduction in sensor data loss under the proposed framework. The SMEP method
      is compared with other methods to validate its effectiveness through experiments
      using real-field sensor data sets. Moreover, based on our experimental results
      and performance comparisons, the SMEP method has been validated to be better than
      others in terms of the average sensor data value error rate caused by sensor data
      loss.

PMID- 28498311
TI  - Differential Immune Responses to New World and Old World Mammalian Arenaviruses.
AB  - Some New World (NW) and Old World (OW) mammalian arenaviruses are emerging,
      zoonotic viruses that can cause lethal hemorrhagic fever (HF) infections in
      humans. While these are closely related RNA viruses, the infected hosts appear to
      mount different types of immune responses against them. Lassa virus (LASV)
      infection, for example, results in suppressed immune function in progressive
      disease stage, whereas patients infected with Junin virus (JUNV) develop overt
      pro-inflammatory cytokine production. These viruses have also evolved different
      molecular strategies to evade host immune recognition and activation. This paper
      summarizes current progress in understanding the differential immune responses to
      pathogenic arenaviruses and how the information can be exploited toward the
      development of vaccines against them.

PMID- 28498313
TI  - Identifying the Genes Regulated by AtWRKY6 Using Comparative Transcript and
      Proteomic Analysis under Phosphorus Deficiency.
AB  - Phosphorus (P) is an important mineral nutrient for plant growth and development.
      Overexpressing AtWRKY6 (35S:WRKY6-9) was more sensitive and wrky6 (wrky6-1) was
      more resistant under low Pi conditions. To better understand the function of
      AtWRKY6 under low phosphate stress conditions, we applied two-dimensional gel
      electrophoresis (2-DE) to analyse differentially expressed proteins in the shoots
      and roots between wild type, 35S:WRKY6-9 and wrky6-1 after phosphorus deficiency
      treatment for three days. The results showed 88 differentially abundant protein
      spots, which were identified between the shoots and roots of 35S:WRKY6-9 and
      wrky6-1 plants. In addition, 59 differentially expressed proteins were identified
      in the leaves and roots of 35S:WRKY6-9 plants. After analysis, 9 genes with W-box
      elements in their promoter sequences were identified in the leaves, while 6 genes
      with W-box elements in their promoter sequences were identified in the roots. A
      total of 8 genes were identified as potential target genes according to the
      quantitative PCR (QPCR) and two dimension difference gel electrophoresis, (2D
      DIGE) results, including ATP synthase, gln synthetase, nitrilase, 14-3-3 protein,
      carbonic anhydrases 2, and tryptophan synthase. These results provide important
      information concerning the AtWRKY6 regulation network and reveal potential vital
      target genes of AtWRKY6 under low phosphorus stress. two dimension difference gel
      electrophoresis, 2D-DIGE.

PMID- 28498314
TI  - Photoactive Hybrid Catalysts Based on Natural and Synthetic Polymers: A
      Comparative Overview.
AB  - In the present review, we would like to draw the reader's attention to the
      polymer-based hybrid materials used in photocatalytic processes for efficient
      degradation of organic pollutants in water. These inorganic-organic materials
      exhibit unique physicochemical properties due to the synergistic effect
      originating from the combination of individual elements, i.e., photosensitive
      metal oxides and polymeric supports. The possibility of merging the structural
      elements of hybrid materials allows for improving photocatalytic performance
      through (1) an increase in the light-harvesting ability; (2) a reduction in
      charge carrier recombination; and (3) prolongation of the photoelectron lifetime.
      Additionally, the great majority of polymer materials exhibit a high level of
      resistance against ultraviolet irradiation and improved corrosion resistance.
      Taking into account that the chemical and environmental stability of the hybrid
      catalyst depends, to a great extent, on the functional support, we highlight
      benefits and drawbacks of natural and synthetic polymer-based photocatalytic
      materials and pay special attention to the fact that the accessibility of
      synthetic polymeric materials derived from petroleum may be impeded due to
      decreasing amounts of crude oil. Thus, it is necessary to look for cheap and
      easily available raw materials like natural polymers that come from, for
      instance, lignocellulosic wastes or crustacean residues to meet the demand of the
      "plastic" market.

PMID- 28498315
TI  - Factors Associated with Stunting among Children Aged 0 to 59 Months from the
      Central Region of Mozambique.
AB  - The objective of this study was to identify the major socio-demographic, health,
      and environmental determinants of stunting among children aged 0-59 months from
      the Tete province (Mozambique) and offering useful information for future
      healthcare strategies and interventions. A case-control study was conducted among
      282 (162 boys; 120 girls) children under five years of age from the central
      region of Mozambique between 1 May and 3 June 2014. Children with stunting (HAZ <
      -2 SD according to the WHO Child Growth Standards in 2006) were considered as
      cases and those who had a Z-score < -2 SD were considered as controls. We
      collected data related to mothers and children and their environment, and they
      were assessed in two groups to find a possible association. The software used for
      data analysis was the SPSS(r)(version, 21.0) using descriptive statistics, t
      test, ANOVA, chi-square analyses, bivariate comparisons, and stepwise multiple
      logistic regression analysis. The results showed that birth weight, mother's
      educational status, maternal occupation, living in a rural area, family size,
      number of children under five years of age in the household, cooking with
      charcoal, inhabiting wooden or straw housing or housing without proper floors,
      overall duration of breastfeeding as well as duration of exclusive breastfeeding,
      and time of initiation of complementary feeding were significantly related to
      stunting. Thus, appropriate nutritional intervention programmes considering these
      determinants and the dissemination of knowledge at the population level related
      to undernutrition are necessary to ameliorate the children's nutritional status.

PMID- 28498316
TI  - Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2
      d]pyrimidine Derivatives Containing Electrophilic Warheads.
AB  - Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively
      studied. However, its 2,6-substituted derivatives are rarely reported. In the
      present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives
      containing electrophilic warheads were designed based on the first known
      Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all
      of the derivatives exhibited negligible activity against FGFR4. However, most of
      the target compounds exhibited antiproliferative activities against four human
      cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12
      showed the most potent antiproliferative activities on the above four cell lines
      with IC50 values of 1.4 MUM, 1.2 MUM, 0.6 MUM, and 2.6 MUM, respectively.
      Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that
      12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary
      structure-activity relationship analysis was discussed based on the experimental
      data.

PMID- 28498317
TI  - Development of Data Registration and Fusion Methods for Measurement of Ultra
      Precision Freeform Surfaces.
AB  - The measurement of ultra-precision freeform surfaces commonly requires several
      datasets from different sensors to realize holistic measurements with high
      efficiency. The effectiveness of the technology heavily depends on the quality of
      the data registration and fusion in the measurement process. This paper presents
      methods and algorithms to address these issues. An intrinsic feature pattern is
      proposed to represent the geometry of the measured datasets so that the
      registration of the datasets in 3D space is casted as a feature pattern
      registration problem in a 2D plane. The accuracy of the overlapping area is
      further improved by developing a Gaussian process based data fusion method with
      full consideration of the associated uncertainties in the measured datasets.
      Experimental studies are undertaken to examine the effectiveness of the proposed
      method. The study should contribute to the high precision and efficient
      measurement of ultra-precision freeform surfaces on multi-sensor systems.

PMID- 28498318
TI  - DNA Methylation Dynamics and Cocaine in the Brain: Progress and Prospects.
AB  - Cytosine modifications, including DNA methylation, are stable epigenetic marks
      that may translate environmental change into transcriptional regulation. Research
      has begun to investigate DNA methylation dynamics in relation to cocaine use
      disorders. Specifically, DNA methylation machinery, including methyltransferases
      and binding proteins, are dysregulated in brain reward pathways after chronic
      cocaine exposure. In addition, numerous methylome-wide and candidate promoter
      studies have identified differential methylation, at the nucleotide level, in
      rodent models of cocaine abuse and drug seeking behavior. This review highlights
      the current progress in the field of cocaine-related methylation, and offers
      considerations for future research.

PMID- 28498319
TI  - CTC-mRNA (AR-V7) Analysis from Blood Samples-Impact of Blood Collection Tube and
      Storage Time.
AB  - Circulating tumour cells (CTCs) are an emerging resource for monitoring cancer
      biomarkers. New technologies for CTC isolation and biomarker detection are
      increasingly sensitive, however, the ideal blood storage conditions to preserve
      CTC-specific mRNA biomarkers remains undetermined. Here we tested the
      preservation of tumour cells and CTC-mRNA over time in common anticoagulant
      ethylene-diamine-tetra-acetic acid (EDTA) and acid citrate dextrose solution B
      (Citrate) blood tubes compared to preservative-containing blood tubes. Blood
      samples spiked with prostate cancer cells were processed after 0, 24, 30, and 48
      h storage at room temperature. The tumour cell isolation efficiency and the mRNA
      levels of the prostate cancer biomarkers androgen receptor variant 7 (AR-V7) and
      total AR, as well as epithelial cell adhesion molecule (EpCAM) were measured.
      Spiked cells were recovered across all storage tube types and times.
      Surprisingly, tumour mRNA biomarkers were readily detectable after 48 h storage
      in EDTA and Citrate tubes, but not in preservative-containing tubes. Notably, AR
      V7 expression was detected in prostate cancer patient blood samples after 48 h
      storage in EDTA tubes at room temperature. This important finding presents
      opportunities for measuring AR-V7 expression from clinical trial patient samples
      processed within 48 h-a much more feasible timeframe compared to previous
      recommendations.

PMID- 28498321
TI  - BDNF Binds Its Pro-Peptide with High Affinity and the Common Val66Met
      Polymorphism Attenuates the Interaction.
AB  - Most growth factors are initially synthesized as precursors then cleaved into
      bioactive mature domains and pro-domains, but the biological roles of pro-domains
      are poorly understood. In the present study, we investigated the pro-domain (or
      pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal
      survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post
      processing product of the precursor BDNF. Using surface plasmon resonance and
      biochemical experiments, we first demonstrated that the BDNF pro-peptide binds to
      mature BDNF with high affinity, but not other neurotrophins. This interaction was
      more enhanced at acidic pH than at neutral pH, suggesting that the binding is
      significant in intracellular compartments such as trafficking vesicles rather
      than the extracellular space. The common Val66Met BDNF polymorphism results in a
      valine instead of a methionine in the pro-domain, which affects human brain
      functions and the activity-dependent secretion of BDNF. We investigated the
      influence of this variation on the interaction between BDNF and the pro-peptide.
      Interestingly, the Val66Met polymorphism stabilized the heterodimeric complex of
      BDNF and its pro-peptide. Furthermore, compared with the Val-containing pro
      peptide, the complex with the Met-type pro-peptide was more stable at both acidic
      and neutral pH, suggesting that the Val66Met BDNF polymorphism forms a more
      stable complex. A computational modeling provided an interpretation to the role
      of the Val66Met mutation in the interaction of BDNF and its pro-peptide. Lastly,
      we performed electrophysiological experiments, which indicated that the BDNF pro
      peptide, when pre-incubated with BDNF, attenuated the ability of BDNF to inhibit
      hippocampal long-term depression (LTD), suggesting a possibility that the BDNF
      pro-peptide may interact directly with BDNF and thereby inhibit its availability.
      It was previously reported that the BDNF pro-domain exerts a chaperone-like
      function and assists the folding of the BDNF protein. However, our results
      suggest a new role for the BDNF pro-domain (or pro-peptide) following proteolytic
      cleave of precursor BDNF, and provide insight into the Val66Met polymorphism.

PMID- 28498322
TI  - Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows
      Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells.
AB  - Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used
      as an anti-cancer drug for various cancers, but the synergistic anti-cancer
      effect of VPA and doxorubicin (DOX) combination treatment and its potential
      underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated.
      Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC
      and identify a specific and efficient, synergistic anti-proliferative effect of
      the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was
      not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the
      coefficient of drug interaction confirmed the significant synergistic effect of
      the combination treatment. Concurrently, the synergistic apoptotic cell death
      caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear
      staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase
      (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species
      (ROS) generation and autophagy, which were clearly attenuated by ROS and
      autophagy inhibitors, respectively. Furthermore, as an indication of the
      mechanism underlying the synergistic effect, we observed that DOX
      internalization, which was induced in the VPA and DOX combination-treated group,
      occurred via by the caveolae-mediated endocytosis pathway. Taken together, our
      study uncovered the potential effect of the VPA and DOX combination treatment
      with regard to cell death, including induction of cellular ROS, autophagy, and
      the caveolae-mediated endocytosis pathway. Therefore, these results present novel
      implications in drug delivery research for the treatment of HCC.

PMID- 28498324
TI  - Geographical Variation in Breast Cancer Outcomes.
AB  - n/a.

PMID- 28498323
TI  - Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity.
AB  - In our ongoing study to evaluate the antiprotozoal activity of alkamides from
      Asteraceae, a dichloromethane extract from the roots of Anacycluspyrethrum L.
      showed a moderate in vitro activity against the NF54 strain of Plasmodium
      falciparum and against Leishmaniadonovani (amastigotes, MHOM/ET/67/L82 strain).
      Seven pure alkamides and a mixture of two further alkamides were isolated by
      column chromatography followed by preparative high performance liquid
      chromatography. The alkamides were identified by mass- and NMR-spectroscopic
      methods as tetradeca-2E,4E-dien-8,10-diynoic acid isobutylamide (anacycline, 1),
      deca-2E,4E-dienoic acid isobutylamide (pellitorine, 2), deca-2E,4E,9-trienoic
      acid isobutylamide (3), deca-2E,4E-dienoic acid 2-phenylethylamide (4), undeca
      2E,4E-dien-8,10-diynoic acid isopentylamide (5), tetradeca-2E,4E,12Z-trien-8,10
      diynoic acid isobutylamide (6), and dodeca-2E,4E-dien acid 4-hydroxy-2
      phenylethylamide (7). Two compounds-undeca-2E,4E-dien-8,10-diynoic acid 2
      phenylethylamide (8) and deca-2E,4E-dienoic acid 4-hydroxy-2-phenylethylamide (9)
      were isolated as an inseparable mixture (1:4). Compounds 3, 4, and 5 were
      isolated from Anacycluspyrethrum L. for the first time. While compounds 4 and 5
      were previously known from the genus Achillea, compound 3 is a new natural
      product, to the best of our knowledge. All isolated alkamides were tested in
      vitro for antiprotozoal activity against Plasmodium falciparum,
      Trypanosomabruceirhodesiense, Trypanosomacruzi, and Leishmaniadonovani and for
      cytotoxicity against L6 rat skeletal myoblasts.

PMID- 28498320
TI  - Chronic Kidney Disease and Exposure to Nephrotoxic Metals.
AB  - Chronic kidney disease (CKD) is a common progressive disease that is typically
      characterized by the permanent loss of functional nephrons. As injured nephrons
      become sclerotic and die, the remaining healthy nephrons undergo numerous
      structural, molecular, and functional changes in an attempt to compensate for the
      loss of diseased nephrons. These compensatory changes enable the kidney to
      maintain fluid and solute homeostasis until approximately 75% of nephrons are
      lost. As CKD continues to progress, glomerular filtration rate decreases, and
      remaining nephrons are unable to effectively eliminate metabolic wastes and
      environmental toxicants from the body. This inability may enhance mortality
      and/or morbidity of an individual. Environmental toxicants of particular concern
      are arsenic, cadmium, lead, and mercury. Since these metals are present
      throughout the environment and exposure to one or more of these metals is
      unavoidable, it is important that the way in which these metals are handled by
      target organs in normal and disease states is understood completely.

PMID- 28498325
TI  - The Health Risk of Cd Released from Low-Cost Jewelry.
AB  - The composition of the surface layer of 13 low-cost jewelry samples with a high
      Cd content was analyzed using an energy-dispersive X-ray fluorescence
      spectrometer (ED XRF). The analyzed jewels were obtained in cooperation with the
      Czech Environmental Inspectorate. The jewels were leached in two types of
      artificial sweat (acidic and alkaline) for 7 days. Twenty microliters of the
      resulting solution was subsequently placed on a paper carrier and analyzed by an
      LIBS (Laser-Induced Breakdown Spectrometry) spectrometer after drying. The Cd
      content in the jewelry surface layer detected by using ED XRF ranged from 13.4%
      to 44.6% (weight per weight-w/w). The samples were subsequently leached in
      artificial alkaline, and the acidic sweat and leachates were analyzed using laser
      induced breakdown spectrometry (LIBS). The amount of released Cd into alkaline
      sweat ranged from 24.0 to 370 ug Cd per week, respectively 3.23-61.7 ug/cm2/week.
      The amount of released Cd into acidic sweat ranged from 16.4 to 1517 ug Cd per
      week, respectively 3.53-253 ug/cm2/week. The limit of Cd for dermal exposure is
      not unequivocally determined in the countries of the EU (European Union) or in
      the U.S. Based on the US EPA (United States Environmental Protection Agency)
      approach used to establish the reference dose (RfD) for Cd contained in food and
      information about the bioavailability of Cd after dermal exposure, we assessed
      our own value of dermal RfD. The value was compared with the theoretical amount
      of Cd, which can be absorbed into the organism from jewelry in contact with the
      skin. The calculation was based on the amount of Cd that was released into acidic
      and alkaline sweat. The highest amount of Cd was released into acidic sweat,
      which represents 0.1% of dermal RfD and into alkaline sweat, 0.5% of dermal RfD.
      These results indicate that the analyzed jewelry contains Cd over the limit for
      composition of jewelry available within the territory of the EU. The determined
      amount of Cd in analyzed jewelry does not, however, pose a threat in terms of
      carcinogenic toxic effects.

PMID- 28498328
TI  - Multilook SAR Image Segmentation with an Unknown Number of Clusters Using a Gamma
      Mixture Model and Hierarchical Clustering.
AB  - This paper presents a novel multilook SAR image segmentation algorithm with an
      unknown number of clusters. Firstly, the marginal probability distribution for a
      given SAR image is defined by a Gamma mixture model (GaMM), in which the number
      of components corresponds to the number of homogeneous regions needed to segment
      and the spatial relationship among neighboring pixels is characterized by a
      Markov Random Field (MRF) defined by the weighting coefficients of components in
      GaMM. During the algorithm iteration procedure, the number of clusters is
      gradually reduced by merging two components until they are equal to one. For each
      fixed number of clusters, the parameters of GaMM are estimated and the optimal
      segmentation result corresponding to the number is obtained by maximizing the
      marginal probability. Finally, the number of clusters with minimum global energy
      defined as the negative logarithm of marginal probability is indicated as the
      expected number of clusters with the homogeneous regions needed to be segmented,
      and the corresponding segmentation result is considered as the final optimal one.
      The experimental results from the proposed and comparing algorithms for simulated
      and real multilook SAR images show that the proposed algorithm can find the real
      number of clusters and obtain more accurate segmentation results simultaneously.

PMID- 28498327
TI  - Structure, Expression, and Functional Analysis of the Hexokinase Gene Family in
      Cassava.
AB  - Hexokinase (HXK) proteins play important roles in catalyzing hexose
      phosphorylation and sugar sensing and signaling. To investigate the roles of HXKs
      in cassava tuber root development, seven HXK genes (MeHXK1-7) were isolated and
      analyzed. A phylogenetic analysis revealed that the MeHXK family can be divided
      into five subfamilies of plant HXKs. MeHXKs were clearly divided into type A
      (MeHXK1) and type B (MeHXK2-7) based on their N-terminal sequences. MeHXK1-5 all
      had typical conserved regions and similar protein structures to the HXKs of other
      plants; while MeHXK6-7 lacked some of the conserved regions. An expression
      analysis of the MeHXK genes in cassava organs or tissues demonstrated that MeHXK2
      is the dominant HXK in all the examined tissues (leaves, stems, fruits, tuber
      phloems, and tuber xylems). Notably, the expression of MeHXK2 and the enzymatic
      activity of HXK were higher at the initial and expanding tuber stages, and lower
      at the mature tuber stage. Furthermore, the HXK activity of MeHXK2 was identified
      by functional complementation of the HXK-deficient yeast strain YSH7.4-3C (hxk1,
      hxk2, glk1). The gene expression and enzymatic activity of MeHXK2 suggest that it
      might be the main enzyme for hexose phosphorylation during cassava tuber root
      development, which is involved in sucrose metabolism to regulate the accumulation
      of starch.

PMID- 28498329
TI  - Low-Cost Nested-MIMO Array for Large-Scale Wireless Sensor Applications.
AB  - In modern communication and radar applications, large-scale sensor arrays have
      increasingly been used to improve the performance of a system. However, the
      hardware cost and circuit power consumption scale linearly with the number of
      sensors, which makes the whole system expensive and power-hungry. This paper
      presents a low-cost nested multiple-input multiple-output (MIMO) array, which is
      capable of providing O ( 2 N 2 ) degrees of freedom (DOF) with O ( N ) physical
      sensors. The sensor locations of the proposed array have closed-form expressions.
      Thus, the aperture size and number of DOF can be predicted as a function of the
      total number of sensors. Additionally, with the help of time-sequence-phase
      weighting (TSPW) technology, only one receiver channel is required for sampling
      the signals received by all of the sensors, which is conducive to reducing the
      hardware cost and power consumption. Numerical simulation results demonstrate the
      effectiveness and superiority of the proposed array.

PMID- 28498326
TI  - A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc
      Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for
      Intervertebral Disc Regeneration.
AB  - The purpose of this study was to develop a quantitative histopathological scoring
      scheme to evaluate disc degeneration and regeneration using an ovine annular
      lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin
      and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc
      structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular
      morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi)
      cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 * 5
      mm lesion; 6 * 20 mm lesion; and 6 * 20 mm lesion plus mesenchymal stem cell
      (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories
      (i-vi) to provide a cumulative score, which underwent statistical analysis using
      STATA software. Focal proteoglycan depletion was associated with 5 * 5 mm annular
      rim lesions, bifurcations, annular delamellation, concentric and radial annular
      tears and an early influx of blood vessels and cells around remodeling lesions
      but the inner lesion did not heal. Similar features in 6 * 20 mm lesions occurred
      over a 3-6-month post operative period. MSCs induced a strong recovery in discal
      pathology with a reduction in cumulative histopathology degeneracy score from
      15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in
      carrier injected discs.

PMID- 28498330
TI  - Specific MicroRNA Pattern in Colon Tissue of Young Children with Eosinophilic
      Colitis.
AB  - Eosinophilic colitis (EC) is a common cause of haematochezia in infants and young
      children. The exact pathomechanism is not understood, and the diagnosis is
      challenging. The role of microRNAs as key class of regulators of mRNA expression
      and translation in patients with EC has not been explored. Therefore, the aim of
      the present study was to explore the miRNA profile in EC with respect to
      eosinophilic inflammation. Patients enrolled in the study (n = 10) had persistent
      rectal bleeding, and did not respond to elimination dietary treatment. High
      throughput microRNA sequencing was carried out on colonic biopsy specimens of
      children with EC (EC: n = 4) and controls (C: n = 4) as a preliminary screening
      of the miRNA profile. Based on the next-generation sequencing (NGS) results and
      literature data, a potentially relevant panel of miRNAs were selected for further
      measurements by real-time reverse transcription (RT)-PCR (EC: n = 14, C: n = 10).
      Validation by RT-PCR resulted in significantly altered expression of miR-21, -31,
      -99b, -125a, -146a, -184, -221, -223, and -559 compared to controls (p <= 0.05).
      Elevation in miR-21, -99b, -146a, -221, and -223 showed statistically significant
      correlation to the extent of tissue eosinophilia. Based on our results, we
      conclude that the dysregulated miRNAs have a potential role in the regulation of
      apoptosis by targeting Protein kinase B/Mechanistic target of rapamycin
      (AKT/mTOR)-related pathways in inflammation by modulating Nuclear factor kappa
      light-chain-enhancer of activated B cells (NF-kappaB)-related signalling and
      eosinophil cell recruitment and activation, mainly by regulating the expression
      of the chemoattractant eotaxin and the adhesion molecule CD44. Our results could
      serve as a basis for further extended research exploring the pathomechanism of
      EC.

PMID- 28498332
TI  - Design, Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase IX
      Inhibitory Evaluations of Novel N-Substituted-beta-d-Glucosamine Derivatives that
      Incorporate Benzenesulfonamides.
AB  - A series of novel N-substituted-beta-d-glucosamine derivatives that incorporate
      benzenesulfonamides were designed using a fragment-based drug design strategy.
      Each derivative was synthesized and evaluated in vitro for its inhibitory
      activity against human carbonic anhydrase (hCA) IX; several derivatives displayed
      desirable potency profiles against this enzyme. The molecular docking studies
      provided the design rationale and predicted potential binding modes for carbonic
      anhydrase (CA) IX and three target compounds, including the most potent
      inhibitor, compound 7f (IC50 = 10.01 nM). Moreover, the calculated Log P (cLog P)
      values showed that all the compounds tended to be hydrophilic. In addition,
      topological polar surface area (TPSA) value-based predictions highlighted the
      selectivity of these carbohydrate-based inhibitors for membrane-associated CA IX.

PMID- 28498331
TI  - The Roles of Glutamine in the Intestine and Its Implication in Intestinal
      Diseases.
AB  - Glutamine, the most abundant free amino acid in the human body, is a major
      substrate utilized by intestinal cells. The roles of glutamine in intestinal
      physiology and management of multiple intestinal diseases have been reported. In
      gut physiology, glutamine promotes enterocyte proliferation, regulates tight
      junction proteins, suppresses pro-inflammatory signaling pathways, and protects
      cells against apoptosis and cellular stresses during normal and pathologic
      conditions. As glutamine stores are depleted during severe metabolic stress
      including trauma, sepsis, and inflammatory bowel diseases, glutamine
      supplementation has been examined in patients to improve their clinical outcomes.
      In this review, we discuss the physiological roles of glutamine for intestinal
      health and its underlying mechanisms. In addition, we discuss the current
      evidence for the efficacy of glutamine supplementation in intestinal diseases.

PMID- 28498334
TI  - Pastoralism versus Agriculturalism-How Do Altered Land-Use Forms Affect the
      Spread of Invasive Plants in the Degraded Mutara Rangelands of North-Eastern
      Rwanda?
AB  - Lantana camara L. (Verbenaceae) originates from tropical Central and South
      America and has become invasive in about 50 countries. It causes problems when
      invading rangelands due to its toxicity to livestock and its tendency to form
      dense, monotonous thickets. Its invasiveness can partly be explained by the high
      tannin content largely protecting the species from being browsed, its tolerance
      to a wide range of environmental conditions, as well as its general preference
      for anthropogenically disturbed habitats. The dispersal of L. camara is
      facilitated by birds and other animals consuming its drupes (endozoochory), and
      so both wild and domestic ungulates could contribute to its spread. In our study,
      we investigated the distribution of L. camara in the Mutara rangelands of north
      eastern Rwanda, an area that faced dramatic landscape changes in recent decades.
      We assessed 23 ecological factors and factors related to land-use and
      conservation-political history. Major effects on the local abundance of L. camara
      were found in that the relative canopy cover of L. camara was negatively
      correlated with the occurrence of other shrubs (suggesting competition for space
      and nutrients), while encounter rates of houses, 'living fences' (Euphorbia
      tirucalli L.) and cattle tracks were positively correlated with L. camara cover.
      Hence, the spread of non-native L. camara in the Mutara rangelands appears to be
      linked to landscape alterations arising from the transformation of rangelands
      supporting traditional pastoralist communities to other agricultural land-use
      forms.

PMID- 28498333
TI  - Hypervalent Iodine Reagents in High Valent Transition Metal Chemistry.
AB  - Over the last 20 years, high valent metal complexes have evolved from mere
      curiosities to being at the forefront of modern catalytic method development.
      This approach has enabled transformations complimentary to those possible via
      traditional manifolds, most prominently carbon-heteroatom bond formation. Key to
      the advancement of this chemistry has been the identification of oxidants that
      are capable of accessing these high oxidation state complexes. The oxidant has to
      be both powerful enough to achieve the desired oxidation as well as provide
      heteroatom ligands for transfer to the metal center; these heteroatoms are often
      subsequently transferred to the substrate via reductive elimination. Herein we
      will review the central role that hypervalent iodine reagents have played in this
      aspect, providing an ideal balance of versatile reactivity, heteroatom ligands,
      and mild reaction conditions. Furthermore, these reagents are environmentally
      benign, non-toxic, and relatively inexpensive compared to other inorganic
      oxidants. We will cover advancements in both catalysis and high valent complex
      isolation with a key focus on the subtle effects that oxidant choice can have on
      reaction outcome, as well as limitations of current reagents.

PMID- 28498335
TI  - The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and
      Restores a Soft Tissue Regeneration In Vivo.
AB  - Autologous fat grafting procedures in plastic surgery have been extensively used
      to reinforce soft tissue in congenital or acquired tissue impairments. With this
      background, the aim of this study is firstly to examine the impact of a selective
      centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile
      maintenance and, secondly, to investigate the effect of restoring volume in
      reconstruction on patients affected by soft tissue damage. After centrifugation,
      the fat graft products were separated into two layers and subsequently examined
      in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73,
      CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were
      performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and
      VIM genes. The results showed that in the middle-high density (MHD) layer there
      was a peak concentration of ASCs, compared to another layer obtained after
      centrifugation. Research carried out on patients under treatment for soft tissue
      regeneration using cells obtained from MHD layer selection will be fundamental in
      comparative analysis. These studies will lead to an adequate standardization of
      outcomes, provided that treatment is performed through cell selection. Therefore,
      a unique procedure in tissue reconstruction and regeneration through fat grafting
      is presented here.

PMID- 28498336
TI  - 11C-Labeling of Aryl Ketones as Candidate Histamine Subtype-3 Receptor PET
      Radioligands through Pd(0)-Mediated 11C-Carbonylative Coupling.
AB  - Pd(0)-mediated coupling between iodoarenes, [11C]carbon monoxide and
      aryltributylstannanes has been used to prepare simple model [11C]aryl ketones.
      Here, we aimed to label four 2-aminoethylbenzofuran chemotype based molecules
      ([11C]1-4) in the carbonyl position, as prospective positron emission tomography
      (PET) radioligands for the histamine subtype 3 receptor (H3R) by adapting this
      methodology with use of aryltrimethylstannanes. Radiosynthesis was successfully
      performed on a platform equipped with a mini-autoclave and a liquid handling
      robotic arm, within a lead-shielded hot-cell. Candidate radioligands were readily
      formulated in saline containing ethanol (10%, v/v) and ascorbic acid (0.5 mg/10
      mL). Yields for preclinical use were in the range of 5-9%, decay-corrected from
      cyclotron-produced [11C]CO2 and molar activities were >115 GBq/umol at end of
      synthesis. Radiochemical purities exceeded >97%.

PMID- 28498337
TI  - Imaging of Early Response to Predict Prognosis in the First-Line Management of
      Follicular Non-Hodgkin Lymphoma with Iodine-131-Rituximab Radioimmunotherapy.
AB  - The purpose of this study was to evaluate prediction of prognosis after first
      line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL),
      by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with
      computed tomography (18F-FDG-PET/CT) three months after induction treatment by
      Iodine-131-rituximab (131I-rituximab). Objective response was determined using
      the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline
      18F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume
      (TMTV). Non-imaging studies included the Follicular lymphoma international
      prognostic index (FLIPI) and absolute baseline monocyte and lymphocyte counts.
      Patients were monitored for over ten years (median follow-up 59 months), and no
      patient was lost to follow-up. Complete response (CR) of 88% predicted excellent
      prognosis with median time-to-next-treatment (TTNT) not yet reached. Those
      patients (12%) who failed to achieve CR (Deauville <= 3) on 18F-FDG-PET/CT at
      three months had significantly poorer outcomes (p < 0.0001) with a median TTNT of
      41 months. Requirement for re-treatment was predicted by FLIPI and absolute
      baseline monocyte count but not lymphocyte count. The TTNT was accurately
      predicted by 18F-FDG-PET/CT Deauville response at three months following first
      line therapy of FL with RIT. Early response demonstrated by imaging does,
      therefore, foretell prognosis in the individual FL patients.

PMID- 28498339
TI  - Easy and Fast Reconstruction of a 3D Avatar with an RGB-D Sensor.
AB  - This paper proposes a new easy and fast 3D avatar reconstruction method using an
      RGB-D sensor. Users can easily implement human body scanning and modeling just
      with a personal computer and a single RGB-D sensor such as a Microsoft Kinect
      within a small workspace in their home or office. To make the reconstruction of
      3D avatars easy and fast, a new data capture strategy is proposed for efficient
      human body scanning, which captures only 18 frames from six views with a close
      scanning distance to fully cover the body; meanwhile, efficient alignment
      algorithms are presented to locally align the data frames in the single view and
      then globally align them in multi-views based on pairwise correspondence. In this
      method, we do not adopt shape priors or subdivision tools to synthesize the
      model, which helps to reduce modeling complexity. Experimental results indicate
      that this method can obtain accurate reconstructed 3D avatar models, and the
      running performance is faster than that of similar work. This research offers a
      useful tool for the manufacturers to quickly and economically create 3D avatars
      for products design, entertainment and online shopping.

PMID- 28498338
TI  - Synthesis, Biological Activity and Preliminary in Silico ADMET Screening of
      Polyamine Conjugates with Bicyclic Systems.
AB  - Polyamine conjugates with bicyclic terminal groups including quinazoline,
      naphthalene, quinoline, coumarine and indole have been obtained and their
      cytotoxic activity against PC-3, DU-145 and MCF-7 cell lines was evaluated in
      vitro. Their antiproliferative potential differed markedly and depended on both
      their chemical structure and the type of cancer cell line. Noncovalent DNA
      binding properties of the most active compounds have been examined using ds-DNA
      thermal melting studies and topo I activity assay. The promising biological
      activity, DNA intercalative binding mode and favorable drug-like properties of
      bis(naphthalene-2-carboxamides) make them a good lead for further development of
      potential anticancer drugs.

PMID- 28498340
TI  - Nutritional Potential of Selected Insect Species Reared on the Island of Sumatra.
AB  - Inhabitants of the Indonesian island of Sumatra are faced with the problem of
      insufficient food supplies and the consequent risk of undernourishment and health
      issues. Edible insects as a traditional and readily available food source could
      be part of the solution. The nutritional value of insects depends on many
      factors, e.g., species, developmental stage, sex, diet, and climatic conditions.
      However, edible insects bred in Sumatra for human consumption have never before
      been assessed with regard to their nutritional value. Our study involved analyses
      of crude protein, chitin, fat and selected fatty acid contents of giant mealworm
      larvae (Zophobas morio), larvae of the common mealworm (Tenebrio molitor) and
      nymphs of the field cricket (Gryllus assimilis). Crude protein content in the
      samples ranged from 46% to 56%. Highest (35%) and lowest (31%) amounts of fat
      were recorded in giant mealworm larvae and larvae of the common mealworm,
      respectively. Chitin amounts ranged from 6% to 13%. Based on these values, which
      are comparable to those known from other food insects reared in different regions
      of the world, the edible species bred in Sumatra could become food sources with a
      potential to help stave off hunger and undernourishment.

PMID- 28498342
TI  - Income-Related Inequalities in Access to Dental Care Services in Japan.
AB  - Background: This study aimed to evaluate whether income-related inequalities in
      access to dental care services exist in Japan. Methods: The subjects included
      beneficiaries of the National Health Insurance (NHI) in Chiba City, Japan, who
      had been enrolled from 1 April 2014 to 31 March 2015. The presence or absence of
      dental visits and number of days spent on dental care services during the year
      were calculated using insurance claims submitted. Equivalent household income was
      calculated using individual income data from 1 January to 31 December 2013,
      declared for taxation. Results: Of the 216,211 enrolled subjects, 50.3% had
      dental care during the year. Among those with dental visits, the average number
      of days (standard deviation) spent on dental care services per year was 7.7
      (7.1). Low income was associated with a decreased rate of dental care utilization
      regardless of age and sex. However, there was a significant inverse linear
      association between the number of days spent on dental care services and income
      levels for both sexes. Conclusions: There were income-related inequalities in
      access to dental care services, regardless of the age group or sex, within the
      Japanese universal health insurance system.

PMID- 28498341
TI  - Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child
      Characteristics, and Maternal Risk Factors in a Second Sample of Rural
      Communities in South Africa.
AB  - Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and
      total fetal alcohol spectrum disorders (FASD) were studied in a second sample of
      three South African rural communities to assess change. Methods: Active case
      ascertainment focused on children with height, weight and/or head circumference
      <=25th centile and randomly-selected children. Final diagnoses were based on
      dysmorphology, neurobehavioral scores, and maternal risk interviews. Results:
      Cardinal facial features, head circumference, and total dysmorphology scores
      differentiated specific FASD diagnostic categories in a somewhat linear fashion
      but all FASD traits were significantly worse than those of randomly-selected
      controls. Neurodevelopmental delays were significantly worse for children with
      FASD than controls. Binge alcohol use was clearly documented as the proximal
      maternal risk factor for FASD, and significant distal risk factors were: low body
      mass, education, and income; high gravidity, parity, and age at birth of the
      index child. FAS rates continue to extremely high in these communities at 9-129
      per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children
      in these communities. Conclusions: Very high rates of FASD persist in these
      general populations where regular, heavy drinking, often in a binge fashion, co
      occurs with low socioeconomic conditions.

PMID- 28498343
TI  - Anti-Helicobacter pylori Activity of Isocoumarin Paepalantine: Morphological and
      Molecular Docking Analysis.
AB  - The Helicobacterpylori bacterium is one of the main causes of chronic gastritis,
      peptic ulcers, and even gastric cancer. It affects an average of half of the
      world population. Its difficult eradication depends upon multi-drug therapy.
      Since its classification as a group 1 carcinogenic by International Agency for
      Research on Cancer (IARC), the importance of H. pylori eradication has obtained a
      novel meaning. There is considerable interest in alternative therapies for the
      eradication of H. pylori using compounds from a wide range of natural products.
      In the present study, we investigated the antibacterial property of the
      isocoumarin paepalantine against H. pylori and it exhibited significant anti-H.
      pylori activity at a minimum inhibitory concentration (MIC) of 128 MUg/mL and at
      a minimum bactericidal concentration (MBC) of 256 MUg/mL. The scanning electron
      microscopy (SEM) revealed significant morphological changes of the bacterial cell
      as a response to a sub-MIC of paepalantine, suggesting a penicillin-binding
      protein (PBP) inhibition. Computational studies were carried out in order to
      study binding modes for paepalantine in PBP binding sites, exploring the active
      and allosteric sites. The data from the present study indicates that paepalantine
      exhibits significant anti-H. pylori activity, most likely by inhibiting membrane
      protein synthesis.

PMID- 28498346
TI  - Power Allocation Based on Data Classification in Wireless Sensor Networks.
AB  - Limited node energy in wireless sensor networks is a crucial factor which affects
      the monitoring of equipment operation and working conditions in coal mines. In
      addition, due to heterogeneous nodes and different data acquisition rates, the
      number of arriving packets in a queue network can differ, which may lead to some
      queue lengths reaching the maximum value earlier compared with others. In order
      to tackle these two problems, an optimal power allocation strategy based on
      classified data is proposed in this paper. Arriving data is classified into
      dissimilar classes depending on the number of arriving packets. The problem is
      formulated as a Lyapunov drift optimization with the objective of minimizing the
      weight sum of average power consumption and average data class. As a result, a
      suboptimal distributed algorithm without any knowledge of system statistics is
      presented. The simulations, conducted in the perfect channel state information
      (CSI) case and the imperfect CSI case, reveal that the utility can be pushed
      arbitrarily close to optimal by increasing the parameter V, but with a
      corresponding growth in the average delay, and that other tunable parameters W
      and the classification method in the interior of utility function can trade power
      optimality for increased average data class. The above results show that data in
      a high class has priorities to be processed than data in a low class, and energy
      consumption can be minimized in this resource allocation strategy.

PMID- 28498345
TI  - Effects of Long-Chain Omega-3 Polyunsaturated Fatty Acids on Endothelial
      Vasodilator Function and Cognition-Are They Interrelated?
AB  - Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain
      functions by acting on endothelial cells in the cerebrovasculature to facilitate
      vasodilatation and perfusion. The aim of this review is to explore this
      hypothesis by analyzing the effect of LCn-3 PUFA supplementation on systemic
      vasodilator and cognitive function and finding evidence to link LCn-3 PUFA
      intake, vasodilator function and cognition. Forty randomized controlled trials
      examining the effect of LCn-3 PUFA supplementation in humans on either
      endothelial vasodilator function or cognition were identified and pooled effects
      measured with a weighted analysis. Compared to placebo, LCn-3 PUFA tended to
      increase flow-mediated dilatation and significantly improved cognitive function.
      Emerging evidence links vasodilator dysfunction to cognitive impairment, but
      evidence that LCn-3 PUFA can improve cognition through enhancements of
      vasodilator function is still lacking. Further research is needed to determine:
      (1) whether LCn-3 PUFA can enhance dilatation of cerebral vessels; (2) if
      improvements in cerebrovascular responsiveness by LCn-3 PUFA are accompanied by
      cognitive benefits; and (3) the target population groups.

PMID- 28498344
TI  - Mercury in Children: Current State on Exposure through Human Biomonitoring
      Studies.
AB  - Mercury (Hg) in children has multiple exposure sources and the toxicity of Hg
      compounds depends on exposure routes, dose, timing of exposure, and developmental
      stage (be it prenatal or postnatal). Over the last decades, Hg was widely
      recognized as a threat to the children's health and there have been
      acknowledgements at the international level of the need of a global policy
      intervention-like the Minamata treaty-aimed at reducing or preventing Hg exposure
      and protecting the child health. National human biomonitoring (HBM) data has
      demonstrated that low levels of exposure of Hg are still an important health
      concern for children, which no one country can solve alone. Although independent
      HBM surveys have provided the basis for the achievements of exposure mitigation
      in specific contexts, a new paradigm for a coordinated global monitoring of
      children's exposure, aimed at a reliable decision-making tool at global level is
      yet a great challenge for the next future. The objective of the present review is
      to describe current HBM studies on Hg exposure in children, taking into account
      the potential pathways of Hg exposure and the actual Hg exposure levels assessed
      by different biomarkers.

PMID- 28498347
TI  - Wireless Sensor Network-Based Service Provisioning by a Brokering Platform.
AB  - This paper proposes a business model for providing services based on the Internet
      of Things through a platform that intermediates between human users and Wireless
      Sensor Networks (WSNs). The platform seeks to maximize its profit through posting
      both the price charged to each user and the price paid to each WSN. A complete
      analysis of the profit maximization problem is performed in this paper. We show
      that the service provider maximizes its profit by incentivizing all users and all
      Wireless Sensor Infrastructure Providers (WSIPs) to join the platform. This is
      true not only when the number of users is high, but also when it is moderate,
      provided that the costs that the users bear do not trespass a cost ceiling. This
      cost ceiling depends on the number of WSIPs, on the value of the intrinsic value
      of the service and on the externality that the WSIP has on the user utility.

PMID- 28498349
TI  - Desalted Duck Egg White Peptides Promote Calcium Uptake and Modulate Bone
      Formation in the Retinoic Acid-Induced Bone Loss Rat and Caco-2 Cell Model.
AB  - Desalted duck egg white peptides (DPs) have been proven to promote calcium uptake
      in Caco-2 cells and rats treated with a calcium-deficient diet. The retinoic acid
      induced bone loss model was used to evaluate the effect of DPs on calcium
      absorption and bone formation. Three-month-old Wistar female rats were treated
      with 0.9% saline, DPs (800 mg/kg), or alendronate (5 mg/kg) for three weeks
      immediately after retinoic acid treatment (80 mg/kg) once daily for two weeks.
      The model group was significantly higher in serum bone alkaline phosphatase than
      the other three groups (p < 0.05), but lower in calcium absorption rate, serum
      osteocalcin, bone weight index, bone calcium content, bone mineral density, and
      bone max load. After treatment with DPs or alendronate, the absorption rate
      increased and some serum and bone indices recovered. The morphology results
      indicated bone tissue form were ameliorated and numbers of osteoclasts decreased
      after supplementation with DPs or alendronate. The in vitro study showed that the
      transient receptor potential vanilloid 6 (TRPV6) calcium channel was the main
      transport pathway of both DPs and Val-Ser-Glu-Glu peptitde (VSEE), which was
      identified from DPs. Our results indicated that DPs could be a promising
      alternative to current therapeutic agents for bone loss because of the promotion
      of calcium uptake and regulation of bone formation.

PMID- 28498350
TI  - Comparison of Direct Sequencing, Real-Time PCR-High Resolution Melt (PCR-HRM) and
      PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) Analysis for Genotyping
      of Common Thiopurine Intolerant Variant Alleles NUDT15 c.415C>T and TPMT c.719A>G
      (TPMT*3C).
AB  - Thiopurine intolerance and treatment-related toxicity, such as fatal
      myelosuppression, is related to non-function genetic variants encoding thiopurine
      S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of
      the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T
      allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G allele) in
      East Asians including Chinese can potentially prevent treatment-related
      complications. Two complementary genotyping approaches, real-time PCR-high
      resolution melt (PCR-HRM) and PCR-restriction fragment length morphism (PCR-RFLP)
      analysis were evaluated using conventional PCR and Sanger sequencing genotyping
      as the gold standard. Sixty patient samples were tested, revealing seven patients
      (11.7%) heterozygous for NUDT15 c.415C>T, one patient homozygous for the variant
      and one patient heterozygous for the TPMT*3C non-function allele. No patient was
      found to harbor both variants. In total, nine out of 60 (15%) patients tested had
      genotypic evidence of thiopurine intolerance, which may require dosage adjustment
      or alternative medication should they be started on azathioprine, mercaptopurine
      or thioguanine. The two newly developed assays were more efficient and showed
      complete concordance (60/60, 100%) compared to the Sanger sequencing results.
      Accurate and cost-effective genotyping assays by real-time PCR-HRM and PCR-RFLP
      for NUDT15 c.415C>T and TPMT*3C were successfully developed. Further studies may
      establish their roles in genotype-informed clinical decision-making in the
      prevention of morbidity and mortality due to thiopurine intolerance.

PMID- 28498348
TI  - Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in
      Chronic Kidney Disease.
AB  - In chronic kidney disease (CKD), accumulation of uremic toxins is associated with
      an increased risk of death. Some uremic toxins are ingested with the diet, such
      as phosphate and star fruit-derived caramboxin. Others result from nutrient
      processing by gut microbiota, yielding precursors of uremic toxins or uremic
      toxins themselves. These nutrients include l-carnitine,
      choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over
      the-counter as nutritional supplements. Physicians and patients alike should be
      aware that, in CKD patients, the use of these supplements may lead to potentially
      toxic effects. Unfortunately, most patients with CKD are not aware of their
      condition. Some of the dietary components may modify the gut microbiota,
      increasing the number of bacteria that process them to yield uremic toxins, such
      as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3
      acetic acid. Circulating levels of nutrient-derived uremic toxins are associated
      to increased risk of death and cardiovascular disease and there is evidence that
      this association may be causal. Future developments may include maneuvers to
      modify gut processing or absorption of these nutrients or derivatives to improve
      CKD patient outcomes.

PMID- 28498351
TI  - Low Family Support and Risk of Obesity among Black Youth: Role of Gender and
      Ethnicity.
AB  - : Most studies on the role of family environment in developing risk of obesity
      among youth have focused on parenting behaviors that are directly involved in
      energy balance in regional, non-representative White samples. Using a national
      sample of ethnically diverse Black youth, the current study tested the
      association between low family support and risk of obesity. We also tested the
      heterogeneity of this association based on gender, ethnicity, and their
      intersection. We used data from the National Survey of American Life-Adolescent
      Supplement (NSAL-A), a national survey of Black adolescents in the United States.
      The study enrolled 1170 African American and Caribbean Black 13-17 year old
      youth. Obesity was defined based on the cutoff points of body mass index (BMI)
      appropriate for age and gender of youth. Family support was measured using a five
      item measure that captured emotional and tangible social support. Age, gender,
      and ethnicity were also measured. Logistic regressions were utilized in the
      pooled sample, and also based on gender, ethnicity, and their intersection, to
      test the link between low family support and risk for obesity. RESULTS: In the
      pooled sample, low family support was not associated with an increased risk of
      obesity (OR = 1.35, 95% Confidence Interval (CI) = 0.96-1.89). The association
      between low family support and risk of obesity was, however, significant among
      African American females (OR = 1.60, 95% CI = 1.01-2.55). There was no
      association for African American males (OR = 1.26, 95% CI = 0.82-1.92), Caribbean
      Black males (OR = 0.68, 95% CI = 0.01-54.85), and Caribbean Black females (OR =
      0.78, 95% CI = 0.42-1.44). In conclusion, policies and programs that enable
      African American families to provide additional family support may prevent
      obesity among African American female youth. Future research should test the
      efficacy of promoting family support as a tool for preventing obesity among
      African American female youth.

PMID- 28498352
TI  - Encapsulation of 16-Hydroxycleroda-3,13-Dine-16,15-Olide in Mesoporous Silica
      Nanoparticles as a Natural Dipeptidyl Peptidase-4 Inhibitor Potentiated
      Hypoglycemia in Diabetic Mice.
AB  - Natural supplements comprise good efficacy with less adverse effects as against
      diabetic therapy, but their advancement as anti-diabetic agents is unsatisfactory
      with regard to the delivery system. Dipeptidyl peptidase-4 (DPP4)/CD26) can
      degrade glucagon-like pepetide-1 (GLP-1) which renders a decrease of blood
      glucose levels. 16-hydroxycleroda-3,13-dine-16,15-olide (HCD) extracted from
      Polyalthia longifolia, exhibits numerous medicinal potentials including
      hypoglycemic potential. On consideration of HCD application, the bioavailability
      is affected by low solubility. Extended experiments of anti-diabetic efficacy
      confirmed HCD biocompatible with mesoporous silica nanoparticles (MSNs)
      encapsulation resulted in a sustained release property in delivering HCD for the
      inhibition of DPP4 via the activity and protein levels of DPP4 analysis. In the
      enzymatic activity assay, MSN-HCD directly changed DPP4 activity. Moreover, MSN
      HCD nanoparticles were treated with Caco-2 cells and the protein levels of DPP4
      determined within the cells. The results revealed that MSN-HCD caused reduction
      of DPP4 activity in a time- and dose-dependent fashion. Orally administered MSN
      HCD in diet-induced diabetic mice alleviated blood glucose via an oral glucose
      tolerance test. In addition, administration of MSN-HCD for five weeks revealed
      that the biochemical cues such as pyruvate transaminase (GPT), glutamate
      oxaloacetate transaminase (GOT), triglycerides (TG), cholesterol (CHO), and
      glycated hemoglobin (HbA1c) in mice were commendable as further confirmation of
      MSN-HCD efficacy and less adverse effects in down-regulation of hyperglycemia.
      Furthermore, this formulation effectively controlled blood glucose and
      significantly decreased the body weight of mice, suggesting that MSN-HCD exerts
      natural DPP4 inhibitor as a potential clinical drug for the treatment of
      diabetes.

PMID- 28498353
TI  - HepPar1-Positive Circulating Microparticles Are Increased in Subjects with
      Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection.
AB  - Circulating microparticles (MPs) are novel potential biomarkers in cancer
      patients. Their role in hepatocellular carcinoma (HCC) is under intensive
      investigation. In this study, we tested the hypothesis that MPs expressing the
      antigen HepPar1 are increased in the blood of subjects with HCC and may serve as
      markers of early recurrence after liver resection (LR). We studied 15 patients
      affected by HCC undergoing LR, and used flow cytometry to assess the number of
      circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and
      five with healthy livers) were used as controls. After LR, HCC patients underwent
      a follow-up to check for early recurrence, which occurred in seven cases. The
      number of circulating HepPar1+ MPs was significantly higher in subjects affected
      by HCC, compared to individuals without cancer (p < 0.01). We also found that,
      among HCC patients, the number of circulating HepPar1+ MPs, measured before LR,
      was significantly higher in those who displayed early recurrence compared to
      those without recurrence (p = 0.02). Of note, other types of circulating MPs,
      such as those derived from endothelial cells (CD144+) or those produced by the
      activated endothelium (CD144+/CD62+), were not associated with HCC, nor could
      they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel
      biomarkers of disease and prognosis in HCC patients.

PMID- 28498354
TI  - Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and
      Staudinger Cycloadditions.
AB  - The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of
      ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at
      the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions
      deliver cis-beta-sultams in considerable amounts, together with the predominant
      trans-beta-sultams. In other cases, the above sulfa-Staudinger cycloadditions
      give rise to trans-beta-sultams exclusively. Further mechanistic rationalization
      discloses that the ortho-nitro effect is attributed to its strong electron
      withdrawing inductive effect. Similarly, the ortho-nitro effect also exists in
      Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current
      research provides further insights into the diastereoselective control in sulfa
      Staudinger and Staudinger cycloadditions.

PMID- 28498355
TI  - The Link between Mastery and Depression among Black Adolescents; Ethnic and
      Gender Differences.
AB  - PURPOSE: Although the link between depression and lower levels of mastery is well
      established, limited information exists on ethnic and gender differences in the
      association between the two. The current study investigated ethnic, gender, and
      ethnic by gender differences in the link between major depressive disorder (MDD)
      and low mastery in the United States. METHODS: We used data from the National
      Survey of American Life-Adolescent supplement (NSAL-A), 2003-2004. In total, 1170
      Black adolescents entered the study. This number was composed of 810 African
      American and 360 Caribbean Black youth (age 13 to 17). Demographic factors,
      socioeconomic status (family income), mastery (sense of control over life), and
      MDD (Composite International Diagnostic Interview, CIDI) were measured. Logistic
      regressions were used to test the association between mastery and MDD in the
      pooled sample, as well as based on ethnicity and gender. RESULTS: In the pooled
      sample, a higher sense of mastery was associated with a lower risk of MDD. This
      association, however, was significant for African Americans but not Caribbean
      Blacks. Similarly, among African American males and females, higher mastery was
      associated with lower risk of MDD. Such association could not be found for
      Caribbean Black males or females. CONCLUSION: Findings indicate ethnic rather
      than gender differences in the association between depression and mastery among
      Black youth. Further research is needed to understand how cultural values and
      life experiences may alter the link between depression and mastery among
      ethnically diverse Black youth.

PMID- 28498356
TI  - Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase
      Ligands Screened Out from Forsythia suspensa Leaves All at One Time.
AB  - It is difficult to screen out as many active components as possible from natural
      plants all at one time. In this study, subfractions of Forsythia suspensa leaves
      were firstly prepared; then, their inhibitive abilities on pancreatic lipase were
      tested; finally, the highest inhibiting subfraction was screened by self-made
      immobilized pancreatic lipase. Results showed that nine ligands, including eight
      inhibitors and one promotor, were screened out all at one time. They were three
      flavonoids (rutin, IC50: 149 +/- 6.0 MUmol/L; hesperidin, 52.4 MUmol/L;
      kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time,
      IC50 notably reached 2.9 +/- 0.5 MUmol/L), two polyphenols (chlorogenic acid,
      3150 +/- 120 MUmol/L; caffeic acid, 1394 +/- 52 MUmol/L), two lignans (phillyrin,
      promoter; arctigenin, 2129 +/- 10.5 MUmol/L), and two phenethyl alcohol
      (forsythiaside A, 2155 +/- 8.5 MUmol/L; its isomer). Their action mechanisms
      included competitive inhibition, competitive promotion, noncompetitive
      inhibition, and uncompetitive inhibition. In sum, using the appropriate methods,
      more active ingredients can be simply and quickly screened out all at one time
      from a complex natural product system. In addition, F. suspensa leaves contain
      numerous inhibitors of pancreatic lipase.

PMID- 28498358
TI  - Three New Indole Diterpenoids from the Sea-Anemone-Derived Fungus Penicillium sp.
      AS-79.
AB  - Three new indolediterpenoids, namely, 22-hydroxylshearinine F (1), 6
      hydroxylpaspalinine (2), and 7-O-acetylemindole SB (3), along with eight related
      known analogs (4-11), were isolated from the sea-anemone-derived fungus
      Penicillium sp. AS-79. The structures and relative configurations of these
      compounds were determined by a detailed interpretation of the spectroscopic data,
      and their absolute configurations were determined by ECD calculations (1 and 2)
      and single-crystal X-ray diffraction (3). Some of these compounds exhibited
      prominent activity against aquatic and human pathogenic microbes.

PMID- 28498357
TI  - Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation,
      Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts.
AB  - Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects
      on metabolism, inflammation, vascular homeostasis, apoptosis and immunity.
      Recently, adiponectin has been suggested to attenuate the progression of human
      dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and
      is thought to be participated in the formation of keloid fibrosis. However, the
      roles played by adiponectin in keloids remain unclear. In this study, we explored
      the effects of adiponectin on CTGF-induced cell proliferation, migration and the
      deposition of extracellular matrix (ECM) and their associated intracellular
      signalling pathways in keloid fibroblasts (KFs). We also explored possible
      mechanisms of keloid pathogenesis. Primary fibroblast cultures were established
      from foreskin biopsies and skin biopsies from patients with keloids. The
      expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by
      reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR,
      immunofluorescence staining, and immunohistochemical analysis. Next, KFs and
      normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence
      of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used
      to examine cell proliferation and migration. The level of the collagen I,
      fibronectin (FN) and alpha-smooth muscle actin (alpha-SMA) mRNAs and proteins
      were determined by quantitative real-time RT-PCR and western blotting. The
      effects of RNA interference (RNAi) targeting the adipoR genes were detected.
      Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase
      (AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase
      protein kinase (PI3K-Akt) were examined by western blotting to further
      investigate the signalling pathways. Furthermore, inhibitors of signal
      transduction pathways were investigated. The expression levels of adiponectin and
      adipoRs were significantly decreased in keloids compared with those in normal
      skin tissue. Adiponectin suppressed the CTGF-induced KFs, but not NFs,
      proliferation, migration and ECM production. Moreover, adiponectin inhibited the
      phosphorylation of AMPK, p38 and extracellular-regulated kinase (ERK), but not
      that of Jun N-terminal kinase (JNK) or Akt, in CTGF-treated KFs. The activity of
      adiponectin-mediated signalling pathways was attenuated by small interfering RNAs
      (siRNAs) targeting adipoR1 (but not siRNAs targeting adipoR2, T-cadherin or
      calreticulin), AMPK (Compound C), p38 (SB203580) inhibitors, and mitogen
      activated protein kinase kinase (MEK) inhibitor (PD98059). Based on our results,
      adiponectin suppresses CTGF-induced KFs proliferation, migration and ECM
      overproduction. One of the underlying mechanisms is the activation of the
      adipoR1, AMPK, p38, and ERK signalling pathways. Therefore, adiponectin may play
      an important role in the progression of keloids, suggesting a potential novel
      target for keloid treatment.

PMID- 28498359
TI  - Assessing the Risk of Hg Exposure Associated with Rice Consumption in a Typical
      City (Suzhou) in Eastern China.
AB  - Recent studies have revealed that not only fish but also rice consumption may
      significantly contribute to human exposure to mercury (Hg) in Asian countries. It
      is therefore essential to assess dietary exposure to Hg in rice and its
      associated health risk. However, risk assessments of Hg in rice in non
      contaminated areas are generally lacking in Asian countries. In the present
      study, Hg concentrations were measured in rice samples collected from markets and
      supermarkets in Suzhou, a typical city in Eastern China. In addition, the rice
      ingestion rates (IR) were assessed via a questionnaire-based survey of Suzhou
      residents. The data were then used to assess the risk of Hg exposure associated
      with rice consumption, by calculating the hazard quotient (HQ). Hg contents in
      rice samples were well below the national standard (20 MUg/kg), ranging from 1.46
      to 8.48 ng/g. They were also significantly (p > 0.05) independent of the area of
      production and place of purchase (markets vs. supermarkets in the different
      districts). Our results indicate a low risk of Hg exposure from rice in Suzhou
      (HQ: 0.005-0.05), despite the generally high personal IR (0.05-0.4 kg/day). The
      risk of Hg associated with rice consumption for Suzhou residents was not
      significantly affected by the age or sex of the consumer (p > 0.05). Overall, our
      results provide a study of human exposure to Hg in rice in Chinese cities not
      known to be contaminated with Hg. Future studies should examine Hg exposure in
      different areas in China and in potentially vulnerable major food types.

PMID- 28498361
TI  - Rectal Cancer in a Patient with Bartter Syndrome: A Case Report.
AB  - A woman with rectal cancer was scheduled for surgery. However, she also had
      hypokalemia, hyperreninemia, and hyperaldosteronism in the absence of any known
      predisposing factors or endocrine tumors. She was given intravenous potassium,
      and her blood abnormalities stabilized after tumor resection. Genetic analysis
      revealed mutations in several genes associated with Bartter syndrome (BS) and
      Gitelman syndrome, including SLC12A1, CLCNKB, CASR, SLC26A3, and SLC12A3.
      Prostaglandin E2 (PGE2) plays an important role in BS and worsens electrolyte
      abnormalities. The PGE2 level is reportedly increased in colorectal cancer, and
      in the present case, immunohistochemical examination revealed an increased PGE2
      level in the tumor. We concluded that the tumor-related PGE2 elevation had
      worsened the patient's BS, which became more manageable after tumor resection.

PMID- 28498360
TI  - Meristem Plant Cells as a Sustainable Source of Redox Actives for Skin
      Rejuvenation.
AB  - Recently, aggressive advertisement claimed a "magic role" for plant stem cells in
      human skin rejuvenation. This review aims to shed light on the scientific
      background suggesting feasibility of using plant cells as a basis of anti-age
      cosmetics. When meristem cell cultures obtained from medicinal plants are exposed
      to appropriate elicitors/stressors (ultraviolet, ultrasound ultraviolet (UV),
      ultrasonic waves, microbial/insect metabolites, heavy metals, organic toxins,
      nutrient deprivation, etc.), a protective/adaptive response initiates the
      biosynthesis of secondary metabolites. Highly bioavailable and biocompatible to
      human cells, low-molecular weight plant secondary metabolites share
      structural/functional similarities with human non-protein regulatory hormones,
      neurotransmitters, pigments, polyamines, amino-/fatty acids. Their redox
      regulated biosynthesis triggers in turn plant cell antioxidant and detoxification
      molecular mechanisms resembling human cell pathways. Easily isolated in
      relatively large quantities from contaminant-free cell cultures, plant
      metabolites target skin ageing mechanisms, above all redox imbalance. Perfect
      modulators of cutaneous oxidative state via direct/indirect antioxidant action,
      free radical scavenging, UV protection, and transition-metal chelation, they are
      ideal candidates to restore photochemical/redox/immune/metabolic barriers,
      gradually deteriorating in the ageing skin. The industrial production of plant
      meristem cell metabolites is toxicologically and ecologically sustainable for
      fully "biological" anti-age cosmetics.

PMID- 28498362
TI  - Caspases and their substrates.
AB  - Protease biology is intimately linked to the functional consequences of substrate
      cleavage events. Human caspases are a family of 12 fate-determining cysteine
      proteases that are best known for driving cell death, either apoptosis or
      pyroptosis. More recently, caspases have been shown to be involved in other
      cellular remodeling events as well including stem cell fate determination,
      spermatogenesis, and erythroid differentiation. Recent global proteomics methods
      enable characterization of the substrates that caspases cleave in live cells and
      cell extracts. The number of substrate targets identified for individual caspases
      can vary widely ranging from only a (few) dozen targets for caspases-4, -5, -9,
      and -14 to hundreds of targets for caspases-1, -2, -3, -6, -7, and -8. Proteomic
      studies characterizing the rates of target cleavage show that each caspase has a
      preferred substrate cohort that sometimes overlaps between caspases, but whose
      rates of cleavage vary over 500-fold within each group. Determining the
      functional consequences of discrete proteolytic events within the global
      substrate pool is a major challenge for the field. From the handful of individual
      targets that have been studied in detail, there are only a few so far that whose
      single cleavage event is capable of sparking apoptosis alone, such as cleavage of
      caspase-3/-7 and BIMEL, or for pyroptosis, gasdermin D. For the most part, it
      appears that cleavage events function cooperatively in the cell death process to
      generate a proteolytic synthetic lethal outcome. In contrast to apoptosis, far
      less is known about caspase biology in non-apoptotic cellular processes, such as
      cellular remodeling, including which caspases are activated, the mechanisms of
      their activation and deactivation, and the key substrate targets. Here we survey
      the progress made in global identification of caspase substrates using proteomics
      and the exciting new avenues these studies have opened for understanding the
      molecular logic of substrate cleavage in apoptotic and non-apoptotic processes.

PMID- 28498363
TI  - A novel microRNA regulator of prostate cancer epithelial-mesenchymal transition.
AB  - The most frequent alteration in the prostate oncogenome is loss of chromosome
      (chr) 8p21 that has been associated with loss of NKX3.1 homeobox gene. Chr8p21
      deletions increase significantly with tumor grade and are associated with poor
      prognosis in prostate cancer (PCa), suggesting critical involvement of this
      region in tumor progression. Recent studies suggest that apart from NKX3.1, this
      region harbors alternative tumor suppressors that are yet undefined. We proposed
      a novel, paradigm shifting hypothesis that this locus is associated with a miRNA
      gene cluster-miR-3622a/b- that plays a crucial suppressive role in PCa. Here we
      demonstrate the crucial role of miR-3622a in prostate cancer epithelial-to
      mesenchymal transition (EMT). MicroRNA expression profiling in microdissected
      human PCa clinical tissues showed that miR-3622a expression is widely
      downregulated and is significantly correlated with poor survival outcome and
      tumor progression. To understand the functional significance of miR-3622a,
      knockdown and overexpression was performed using non-transformed prostate
      epithelial and PCa cell lines, respectively, followed by functional assays. Our
      data demonstrate that endogenous miR-3622a expression is vital to maintain the
      epithelial state of normal and untransformed prostate cells. miR-3622a expression
      inhibits EMT, progression and metastasis of PCa in vitro and in vivo. Further, we
      found that miR-3622a directly targets EMT effectors ZEB1 and SNAI2. In view of
      these data, we propose that frequent loss of miR-3622a at chr8p21 region leads to
      induction of EMT states that in turn, promotes PCa progression and metastasis.
      This study has potentially significant implications in the field of prostate
      cancer as it identifies an important miRNA component of a frequently lost
      chromosomal region with critical roles in prostate carcinogenesis which is a
      highly significant step towards understanding the mechanistic involvement of this
      locus. Also, our study indicates that miR-3622a is a novel PCa biomarker and
      potential drug target for developing therapeutic regimens against advanced PCa.

PMID- 28498364
TI  - Convergence of mitochondrial and chloroplastic ANAC017/PAP-dependent retrograde
      signalling pathways and suppression of programmed cell death.
AB  - The energy-converting organelles mitochondria and chloroplasts are tightly
      embedded in cellular metabolism and stress response. To appropriately control
      organelle function, extensive regulatory mechanisms are at play that involve two
      way exchange between the nucleus and mitochondria/chloroplasts. In recent years,
      our understanding of how mitochondria and chloroplasts provide 'retrograde'
      feedback to the nucleus, resulting in targeted transcriptional changes, has
      greatly increased. Nevertheless, mitochondrial and chloroplast retrograde
      signalling have largely been studied independently, and only few points of
      interaction have been found or proposed. Through reassessment of recent
      publications, this perspective proposes that two of the most well-studied
      retrograde signalling pathways in plants, those mediated by ANAC017 and those
      mediated by phosphoadenosine phosphate (PAP), are most likely convergent and can
      direct overlapping genes. Furthermore, at least part of this common retrograde
      response appears targeted towards suppression of programmed cell death (PCD)
      triggered by organellar defects. The identified target genes are discussed in
      light of their roles in PCD suppression and amplifying the signalling cascade via
      positive-feedback loops. Finally, a mechanism is proposed that may explain why
      the convergence of PAP/ANAC017-dependent signalling appears capable of
      suppressing some types of PCD lesions, but not others, based on the subcellular
      location of the initial PCD-inducing dysfunction.

PMID- 28498366
TI  - Till stress do us ataRT: a novel toxin-antitoxin system targeting translation
      initiation.

PMID- 28498365
TI  - Inhibition of Twist1-mediated invasion by Chk2 promotes premature senescence in
      p53-defective cancer cells.
AB  - Twist1, a basic helix-loop-helix transcription factor is implicated as a key
      mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination
      in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a
      major cell cycle regulatory protein provides a barrier to tumorigenesis due to
      DNA damage response by preserving genomic stability of the cells. Here we
      demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering
      and invadopodia formation ability of p53-mutated invasive cells by suppressing
      Twist1, indicating Chk2 confers vital role in metastasis prevention. In addition,
      ectopic Chk2, as well as its (Chk2) induction by natural podophyllotoxin analog,
      4'-demethyl-deoxypodophyllotoxin glucoside (4DPG), strongly restrain Twist1
      activity along with other mesenchymal markers, for example, ZEB-1, vimentin and
      Snail1, whereas the epithelial markers such as E-cadherin and TIMP-1 expression
      augmented robustly. However, downregulation of endogenous Chk2 by siRNA as well
      as Chk2 selective inhibitor PV1019 implies that 4DPG-mediated inhibition of
      Twist1 is Chk2-dependent. Further, mechanistic studies unveil that Chk2
      negatively regulates Twist1 promoter activity and it (Chk2) interacts steadily
      with Snail1 protein to curb EMT. Strikingly, Chk2 overexpression triggers
      premature senescence in these cells with distinctive increase in senescence
      associated beta-galactosidase (SA-beta-gal) activity, G2/M cell cycle arrest and
      induction of senescence-specific marker p21waf1/Cip1. Importantly, stable
      knockdown of Twist1 by shRNA markedly augments p21 expression, its nuclear
      accumulation, senescence-associated heterochromatin foci (SAHF) and amplifies the
      number of SA-beta-gal-positive cells. Moreover, our in vivo studies also validate
      that 4DPG treatment significantly abrogates tumor growth as well as metastatic
      lung nodules formation by elevating the level of phospho-Chk2, Chk2 and
      suppressing Twist1 activity in mouse mammary carcinoma model. In a nutshell, this
      report conceives a novel strategy of Twist1 suppression through Chk2 induction,
      which prevents metastatic dissemination and promotes premature senescence in p53
      defective invasive cancer cells.

PMID- 28498368
TI  - It is a differentiation game: STAT5 in a new role.

PMID- 28498369
TI  - Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of
      MTP18 expression.
AB  - Circular RNAs (circRNAs) have important roles in several cellular processes. No
      study has established the pathophysiological role for circRNAs in the heart.
      Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA
      (MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly
      targeting and downregulating miR-652-3p; this in turn blocks mitochondrial
      fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18
      deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis
      and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial
      fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly
      sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown
      in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results
      reveal a crucial role for circRNA in regulating mitochondrial dynamics and
      apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic
      avenue for cardiovascular diseases.

PMID- 28498367
TI  - Initiation and execution mechanisms of necroptosis: an overview.
AB  - Necroptosis is a form of regulated cell death, which is induced by ligand binding
      to TNF family death domain receptors, pattern recognizing receptors and virus
      sensors. The common feature of these receptor systems is the implication of
      proteins, which contain a receptor interaction protein kinase (RIPK) homology
      interaction motif (RHIM) mediating recruitment and activation of receptor
      interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis
      executioner mixed lineage kinase domain-like (MLKL). In case of the TNF family
      members, the initiator is the survival- and cell death-regulating RIPK1 kinase,
      in the case of Toll-like receptor 3/4 (TLR3/4), a RHIM-containing adaptor, called
      TRIF, while in the case of Z-DNA-binding protein ZBP1/DAI, the cytosolic viral
      sensor itself contains a RHIM domain. In this review, we discuss the different
      protein complexes that serve as nucleation platforms for necroptosis and the
      mechanism of execution of necroptosis. Transgenic models (knockout, kinase-dead
      knock-in) and pharmacologic inhibition indicate that RIPK1, RIPK3 or MLKL are
      implicated in many inflammatory, degenerative and infectious diseases. However,
      the conclusion of necroptosis being solely involved in the etiology of diseases
      is blurred by the pleiotropic roles of RIPK1 and RIPK3 in other cellular
      processes such as apoptosis and inflammasome activation.

PMID- 28498371
TI  - Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP
      treated patients with diffuse large B-cell lymphoma.

PMID- 28498370
TI  - Validation of response assessment according to international consortium for
      MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypomethylating
      agents.

PMID- 28498372
TI  - Comparative transcriptomics analyses reveal the conservation of an ancestral
      infectious strategy in two bacteriophage genera.
AB  - Although the evolution of tailed bacteriophages has increasingly been better
      understood through comparisons of their DNA sequences, the functional
      consequences of this evolution on phage infectious strategies have remained
      unresolved. In this study, we comprehensively compared the transcriptional
      strategies of two related myoviruses, PAK_P3 and PAK_P4, infecting the same
      Pseudomonas aeruginosa host strain. Outside of the conservation of their
      structural clusters, their highly syntenic genomes display only limited DNA
      similarity. Despite this apparent divergence, we found that both viruses follow a
      similar infection scheme, relying on a temporal regulation of their gene
      expression, likely involving the use of antisense transcripts, as well as a rapid
      degradation of 90% of the host non-ribosomal mRNA, as previously reported for
      PAK_P3. However, the kinetics of the mRNA degradation is remarkably faster during
      PAK_P4 infection. Moreover, we found that each virus has evolved specific
      adaptations, as exemplified by the distinct patterns of their core genes
      expression as well as the specific manipulation of the expression of iron-related
      host genes by PAK_P4. This study enhances our understanding of the evolutionary
      process of virulent phages, which relies on adjusting globally conserved
      ancestral infection mechanisms.

PMID- 28498373
TI  - Genomic exploration of individual giant ocean viruses.
AB  - Viruses are major pathogens in all biological systems. Virus propagation and
      downstream analysis remains a challenge, particularly in the ocean where the
      majority of their microbial hosts remain recalcitrant to current culturing
      techniques. We used a cultivation-independent approach to isolate and sequence
      individual viruses. The protocol uses high-speed fluorescence-activated virus
      sorting flow cytometry, multiple displacement amplification (MDA), and downstream
      genomic sequencing. We focused on 'giant viruses' that are readily
      distinguishable by flow cytometry. From a single-milliliter sample of seawater
      collected from off the dock at Boothbay Harbor, ME, USA, we sorted almost 700
      single virus particles, and subsequently focused on a detailed genome analysis of
      12. A wide diversity of viruses was identified that included Iridoviridae,
      extended Mimiviridae and even a taxonomically novel (unresolved) giant virus. We
      discovered a viral metacaspase homolog in one of our sorted virus particles and
      discussed its implications in rewiring host metabolism to enhance infection. In
      addition, we demonstrated that viral metacaspases are widespread in the ocean. We
      also discovered a virus that contains both a reverse transcriptase and a
      transposase; although highly speculative, we suggest such a genetic complement
      would potentially allow this virus to exploit a latency propagation mechanism.
      Application of single virus genomics provides a powerful opportunity to
      circumvent cultivation of viruses, moving directly to genomic investigation of
      naturally occurring viruses, with the assurance that the sequence data is virus
      specific, non-chimeric and contains no cellular contamination.

PMID- 28498374
TI  - Ranibizumab pretreatment in diabetic vitrectomy: a pilot randomised controlled
      trial (the RaDiVit study).
AB  - PurposeOur aim was to evaluate the impact of intravitreal ranibizumab
      pretreatment on the outcome of vitrectomy surgery for advanced proliferative
      diabetic retinopathy. The objective was to determine the feasibility of a
      subsequent definitive trial and estimate the effect size and variability of the
      outcome measure.Patients and methodsWe performed a pilot randomised double-masked
      single-centre clinical trial in 30 participants with tractional retinal
      detachment associated with proliferative diabetic retinopathy. Seven days prior
      to vitrectomy surgery, participants were randomly allocated to receive either
      intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK)
      or subconjunctival saline (control). The primary outcome was best-corrected
      visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual
      acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in
      the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the
      control group and by 24 (27) letters in the ranibizumab group. We found no
      difference in the progression of tractional retinal detachment prior to surgery,
      the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage
      persisted at 12 weeks in two of the control group but none of the ranibizumab
      group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy
      surgery for advanced proliferative diabetic retinopathy by reducing the extent of
      post-operative vitreous cavity haemorrhage. However, the effect size appears to
      be modest; we calculate that a definitive study to establish a minimally
      important difference of 5.9 letters at a significance level of P<0.05 would
      require 348 subjects in each arm.

PMID- 28498376
TI  - Two isomorphous Co(ii) coordination polymers based on new alpha,alpha
      disubstituted derivatives of zoledronic acid: synthesis, structures and
      properties.
AB  - Two novel alpha,alpha-disubstituted derivatives of zoledronic acid, namely 1
      hydroxy-2-(1H-imidazol-1-yl)-2-methylpropylidene-1,1-diphosphonic acid (H4L1) and
      1-hydroxy-2-[1-(1H-imidazol-1-yl)cyclopropyl]ethylidene-1,1-diphosphonic acid
      (H4L2) were synthesized and structurally characterized by single-crystal X-ray
      diffraction. The reaction of cobalt acetate with H4L1 and H4L2 carried out under
      hydrothermal conditions afforded two isomorphous Co3(HL1)2(H2O)6.6H2O (1a) and
      Co3(HL2)2(H2O)6.6H2O (2a) complexes. Both compounds are characterized by means of
      X-ray crystallography, IR and NIR-Vis-UV spectroscopic methods. Furthermore,
      their magnetic properties and thermal stabilities are reported. The crystals of
      1a and 2a feature infinite 1D polymeric chains built from alternately arranged
      dinuclear [Co2(HL1/HL2)(H2O)2]2 units and {Co1O6} octahedra running along the
      [1[combining macron]10] crystallographic direction. In both compounds,
      crystallographically distinct Co1 and Co2 atoms are six-coordinated. As is
      reflected in T values (T - index of tetragonality), the coordination environment
      of Co1 generates a slightly elongated octahedron (T = 0.94), whereas a slightly
      compressed octahedron (T = 1.06 for 1a and 1.05 for 2a) is formed around Co2. An
      assumption that the d-d type absorption is mainly attributed to the inversion
      related Co2 centers, whose population is two times higher than that of Co1,
      afforded a good correlation between calculated transition energies and
      experimental NIR-Vis-UV spectra. The magnetic susceptibility measurements
      analyzed in terms of a spin-3/2 Heisenberg trimer chain revealed that Co1Co2
      interactions within the trimer are antiferromagnetic whereas Co2Co2 intertrimer
      interactions are ferromagnetic.

PMID- 28498375
TI  - Neuro-ophthalmologic manifestations of cholangiocarcinoma: a case series.
AB  - PurposeTo describe the neuro-ophthalmologic findings of
      cholangiocarcinoma.MethodsWe report a retrospective chart review of
      cholangiocarcinoma patients presenting at two tertiary care centers in the Texas
      Medical Center.ResultsFive patients with neuro-ophthalmologic symptoms related to
      cholangiocarcinoma were identified. One patient presented with diplopia due to
      metastasis to the left medial rectus muscle, two patients had metastasis to the
      occipital lobe resulting in homonymous hemianopsia, one patient had involvement
      of the clivus resulting in sixth nerve palsy, and one presented with a
      hypercoagulable state-related stroke causing a homonymous hemianopsia and visual
      hallucinations.ConclusionsNeuro-ophthalmic manifestations of cholangiocarcinoma
      depend upon both mechanism and localization. We report five cases of
      cholangiocarcinoma with neuro-ophthalmologic findings. To our knowledge, this is
      the largest such series reported in the English language ophthalmic literature.

PMID- 28498377
TI  - Broadband ultrafast photovoltaic detectors based on large-scale topological
      insulator Sb2Te3/STO heterostructures.
AB  - Topological insulators (TIs) are new states of quantum matter in which the spin
      momentum-locked surface states reside in the bulk insulating gap and have
      triggered extensive investigations on fundamental properties and potential
      applications. Herein, we report scalable, broadband photovoltaic detectors based
      on the topological insulator Sb2Te3/strontium titanate (STO) heterostructure.
      Large-scale (2 mm * 5 mm), high crystalline quality p-type Sb2Te3 films were
      fabricated on an n-type STO substrate by the molecular beam epitaxy (MBE) method.
      The Sb2Te3/STO heterostructures exhibited pronounced photovoltaic behavior in a
      wide range of temperatures as a result of a strong built-in field at the hetero
      interface. Superior performances of broadband (from visible to infrared, 405 nm
      1550 nm) and ultrafast (rise time ~30 MUs, fall time ~95 MUs) photoresponses were
      achieved under ambient conditions. The prominent repeatability and stability
      indicated that our photodetectors can operate effectively in harsh circumstances.
      These results show that stacking the topological insulator thin films on a
      strongly correlated oxide substrate using the MBE approach holds great promise
      for high performance optoelectronic applications.

PMID- 28498378
TI  - Reconfigurable optical manipulation by phase change material waveguides.
AB  - Optical manipulation by dielectric waveguides enables the transportation of
      particles and biomolecules beyond diffraction limits. However, traditional
      dielectric waveguides could only transport objects in the forward direction which
      does not fulfill the requirements of the next generation lab-on-chip system where
      the integrated manipulation system should be much more flexible and
      multifunctional. In this work, bidirectional transportation of objects on the
      nanoscale is demonstrated on a rectangular waveguide made of the phase change
      material Ge2Sb2Te5 (GST) by numerical simulations. Either continuous pushing
      forces or pulling forces are generated on the trapped particles when the GST is
      in the amorphous or crystalline phase. With the technique of a femtosecond laser
      induced phase transition on the GST, we further proposed a reconfigurable optical
      trap array on the same waveguide. This work demonstrates GST waveguide's
      potential of achieving multifunctional manipulation of multiple objects on the
      nanoscale with plausible optical setups.

PMID- 28498379
TI  - Non-pericyclic cycloaddition of gem-difluorosubstituted azomethine ylides to the
      C[double bond, length as m-dash]O bond: computational study and synthesis of
      fluorinated oxazole derivatives.
AB  - The cycloaddition of arenecarbaldehydes and alpha,alpha,alpha
      trifluoroacetophenones with gem-difluoro-substituted azomethine ylides, generated
      from N-benzhydrylideneamines and difluorocarbene, occurs regioselectively to
      give, after hydrolysis, oxazolidin-4-ones. The primary cycloadducts of
      trifluoroacetophenones, 4,4-difluoro-5-trifluoromethyloxazolidine derivatives,
      are sufficiently stable to be isolated in reasonable to excellent yields. The
      results of correlation analysis and DFT calculations reveal a non-pericyclic step
      wise mechanism of the reaction. The replacement of the two geminal hydrogen atoms
      in the azomethine ylide intermediate for fluorine atoms results in a dramatic
      change in the reaction mechanism from pericyclic to step-wise, proceeding via a
      zwitterion-like transition state in which no C-O bonding is observed.

PMID- 28498380
TI  - Helix-sense-selective co-precipitation for preparing optically active helical
      polymer nanoparticles/graphene oxide hybrid nanocomposites.
AB  - Constructing optically active helical polymer based nanomaterials without using
      expensive and limited chirally helical polymers has become an extremely
      attractive research topic in both chemical and materials science. In this study,
      we prepared a series of optically active helical polymer nanoparticles/graphene
      oxide (OAHPNs/GO) hybrid nanocomposites through an unprecedented strategy-the co
      precipitation of optically inactive helical polymers and chirally modified GO.
      This approach is named helix-sense-selective co-precipitation (HSSCP), in which
      the chirally modified GO acted as a chiral source for inducing and further
      stabilizing the predominantly one-handed helicity in the optically inactive
      helical polymers. SEM and TEM images show quite similar morphologies of all the
      obtained OAHPNs/GO nanocomposites; specifically, the chirally modified GO sheets
      were uniformly decorated with spherical polymer nanoparticles. Circular dichroism
      (CD) and UV-vis absorption spectra confirmed the preferentially induced helicity
      in the helical polymers and the optical activity of the nanocomposites. The
      established HSSCP strategy is thus proven to be widely applicable and is expected
      to produce numerous functional OAHPNs/GO nanocomposites and even the analogues.

PMID- 28498381
TI  - A theoretical study of the light-induced cross-linking reaction of 5-fluoro-4
      thiouridine with thymine.
AB  - In contrast to photophysics of thio-substituted nucleobases, their photoinduced
      cross-linking reactions with canonical nucleobases remain scarcely investigated
      computationally. In this work, we have adopted combined CASPT2/PCM//CASSCF and
      B3LYP-D3/PCM electronic structure methods to study this kind of photochemical
      reaction of 5-fluoro-4-thiouridine (truncated 5-fluoro-1-methyl-4-thiouracil used
      in calculations) and 1-methylthymine (referred to as thymine for clarity
      hereinafter). On the basis of CASPT2/PCM computed results, we have proposed two
      efficient excited-state relaxation pathways to populate the lowest T1 state of
      the complex of 5-fluoro-1-methyl-4-thiouracil and thymine from its initially
      populated S2(1pipi*) state. In the first one, the S2 system first hops to the S1
      state via an S2/S1 conical intersection, followed by a direct S1 -> T1
      intersystem crossing process enhanced by large S1/T1 spin-orbit coupling. In the
      second path, the resultant S1 system first jumps to the T2 state, from which an
      efficient T2 -> T1 internal conversion occurs. The T1 cross-linking reaction is
      overall divided into two phases. The first phase is a stepwise and nonadiabatic
      photocyclization reaction, which starts from the T1 complex and ends up with an
      S0 thietane intermediate. The second phase is a thermal reaction. The system
      first rearranges its four- and six-membered rings to form three new rings; then,
      an S0 fluorine atom transfer occurs, followed by the formation of photoproducts.
      Finally, the present work paves the way for studying light-induced cross-linking
      reactions of thionucleobases with canonical bases in DNA and RNA.

PMID- 28498382
TI  - Rapid assembly of the doubly-branched pentasaccharide domain of the
      immunoadjuvant jujuboside A via convergent B(C6F5)3-catalyzed glycosylation of
      sterically-hindered precursors.
AB  - A convergent synthesis of the complex, doubly-branched pentasaccharide domain of
      the natural-product immunoadjuvant jujuboside A is described. The key step is a
      sterically-hindered glycosylation reaction between a branched trisaccharide
      trichloroacetimidate glycosyl donor and a disaccharide glycosyl acceptor.
      Conventional Lewis acids (TMSOTf, BF3.Et2O) were ineffective in this
      glycosylation, but B(C6F5)3 catalyzed the reaction successfully. Inherent
      complete diastereoselectivity for the undesired alpha-anomer was overcome by
      rational optimization with a nitrile solvent system (1 : 5 t-BuCN/CF3Ph) to
      provide flexible, effective access to the beta-linked pentasaccharide.

PMID- 28498384
TI  - Highly efficient oxygen evolution from CoS2/CNT nanocomposites via a one-step
      electrochemical deposition and dissolution method.
AB  - The oxygen evolution reaction (OER) has been viewed as a critical step in
      electrochemical energy conversion and storage devices. However, searching for
      cheap and efficient OER electrocatalysts still remains an urgent task. Herein, we
      develop a new strategy involving a one-step electrochemical deposition and
      dissolution method to fabricate hydrophilic porous CoS2/carbon nanotube (CNT)
      composites (CNT-CoS2). X-ray photoelectron spectroscopy and near-edge X-ray
      absorption fine structure spectroscopy measurements confirm the formation of
      hydrophilic groups on the surface of the porous CoS2 during electrochemical
      oxidation. Our design holds several advantages. The electricity conductivity of
      CoS2 is increased by introducing CNTs as a conductive substrate. The porous
      nanostructures of CoS2 increase its surface area, and provide paths to promote
      charge and reactant transfer. The active edge sites modified with hydrophilic
      groups can increase the content of electrolyte-electrode contact points,
      increasing the intrinsic catalytic performance of CoS2. These factors allow CNT
      CoS2 to achieve a low onset potential of 1.33 V vs. RHE, a stable current density
      (j) of 10 mA cm-2 at an overpotential of 290 mV, and excellent stability under
      alkaline conditions compared to that of IrO2. The comprehensive performance of
      the CNT-CoS2 electrocatalyst is comparable to or better than that of any reported
      noble metal-free OER catalyst, even RuO2 and IrO2. This facile synthesis strategy
      involving synchronous electrochemical deposition and dissolution should be easily
      adapted for large-scale water electrolysis.

PMID- 28498385
TI  - Polymer brushes based on PLLA-b-PEO colloids for the preparation of protein
      resistant PLA surfaces.
AB  - In this study we investigate the formation of protein-resistant polymer surfaces,
      such as aliphatic polyesters, through the deposition of self-assemblies of
      amphiphilic poly(l-lactide)-b-poly(ethylene oxide), PLLA-b-PEO, copolymers as
      stable nanoparticles with a kinetically frozen PLLA core on model PLLA surfaces.
      The length of the PEO chains in the corona was tuned to achieve polymer brushes
      capable of preventing protein adsorption on PLA-based biomaterials. The
      spectroscopic ellipsometry, IR and XPS analysis, contact angle goniometry, and
      AFM proved that the PEO chains adopted a brush structure and were preferably
      exposed on the surface. The low-fouling properties of the physisorbed PLLA-b-PEO
      layers approached the ones of reactive grafting methods, as shown by surface
      plasmon resonance spectroscopy. The anti-fouling properties of the prepared PEO
      brushes provided sufficient interface to prevent cell adhesion as proved in
      vitro. Thus, the developed surface coating with PLLA-b-PEO colloids can provide
      an anti-fouling background for the creation of nanopatterned biofunctionalized
      surfaces in biomedical applications.

PMID- 28498387
TI  - The Need for Linguistically and Culturally Adapted Standard Questionnaires to
      Assess Itch: A Preliminary Study.

PMID- 28498386
TI  - Atorvastatin inhibits cholesterol-induced caspase-3 cleavage through down
      regulation of p38 and up-regulation of Bcl-2 in the rat carotid artery.
AB  - AIM: Atherosclerotic lesions in the carotid arteries lead to a broad range of
      cerebrovascular disorders such as vascular dementia and ischaemic stroke. Recent
      studies have verified the beneficial role of atorvastatin (AV) in
      atherosclerosis. Despite a large body of studies, the mechanisms underlying this
      effect have not been completely explained. In this study, several experiments
      were performed on atherosclerotic rat models to investigate the anti-inflammatory
      and anti-apoptotic effect of AV in the carotid artery. METHODS: In this
      experimental study, 40 male Wistar rats (250 +/- 25 g) were randomly divided into
      four groups: rats on a normal diet (ND; n = 10); a high-cholesterol diet (HD; n =
      10); a high-cholesterol diet plus AV (HD + AV; n = 10) ; and the AV control group
      (AV; n = 10). Cleavage of caspase-3 protein, expression of B-cell lymphoma 2 (Bcl
      2) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) were
      determined by immunoblotting assay in the carotid artery homogenate. Plasma
      atherogenic indices, including total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured
      by colorimetric assay at the end of the experiment. Plasma levels of oxidised LDL
      (oxLDL) were measured by sandwich enzyme-linked immunosorbent assay (ELISA).
      RESULTS: After eight weeks of feeding with a high-cholesterol diet, an elevated
      level of oxLDL was observed in the plasma in the HD group compared with the ND
      group [214.42 +/- 17.46 vs 69.13 +/- 9.92 mg/dl (5.55 +/- 0.45 vs 1.78 +/- 0.26
      mmol/l); p < 0.01]. AV administration significantly reduced oxLDL levels in the
      HD + AV compared to the HD group [126.52 +/- 9.46 vs 214.42 +/- 17.46 mg/dl (3.28
      +/- 0.25 vs 5.55 +/- 0.45 mmol/l); p < 0.01]. Results also showed that compared
      with the HC group, the HC + AV group had lower levels of p38 phosphorylation (p <
      0.05) and higher levels of Bcl-2 expression (p < 0.05). Lower levels of cleaved
      caspase-3 were observed in the HC + AV group in comparison with the HC group (p <
      0.05). CONCLUSIONS: The resultant data suggest that the anti-apoptotic effect of
      AV could be partially mediated by the pro-inflammatory protein p38 MAPK and the
      anti-apoptotic protein Bcl-2 in the rat carotid artery. Atorvastatin can
      therefore be considered a target drug in the prevention or development of
      atherosclerotic events.

PMID- 28498388
TI  - Chronic Pain in Patients with Skin Disorders.

PMID- 28498389
TI  - Next-generation Sequencing Identified a Novel EDA Mutation in a Chinese Pedigree
      of Hypohidrotic Ectodermal Dysplasia with Hyperplasia of the Sebaceous Glands.

PMID- 28498390
TI  - Substrate stiffness affects epithelial-mesenchymal transition of cervical cancer
      cells through miR-106b and its target protein DAB2.
AB  - The effects of different substrate stiffness were investigated on epithelial
      mesenchymal transition (EMT) of cervical cancer cell lines and the role of miR
      106b and its target protein DAB2 therein. Cervical cancer cell lines HeLa and
      SiHa were cultured on artificial substrates with different stiffness prepared
      using different ratios of acrylamide and bis-acrylamide. Changes of microRNA
      profiles were detected using microRNA chip analysis, and the expression levels of
      EMT-related markers E-cadherin and vimentin were detected using western blotting
      and real-time PCR. In addition, the effects of miR-106b overexpression as well as
      miR-106b and DAB2 knockdown on expression of E-cadherin and vimentin were also
      examined using western blotting and real-time PCR. The results showed that i)
      cervical cancer cell lines SiHa and HeLa cultured on substrate with stiffness of
      20 kPa had the strongest EMT ability, showed the highest levels of vimentin and
      lowest levels of E-cadherin, compared with cells cultured on substrate with
      stiffness of 1 kPa; ii) miR-106b knockdown reversed the effects of substrate
      stiffness on EMT of cervical cancer cells, while miR-106 overexpression and DAB2
      knockdown induced EMT of cervical cancer cells cultured on substrate with
      stiffness of 20 kPa. Overall, the results indicated that substrate stiffness
      could regulate EMT of cervical cancer cell lines HeLa and SiHa at least partially
      through miR-106b and its downstream target DAB2.

PMID- 28498391
TI  - Hypospadias in a male infant with an unusual mosaic 45,X/46,X,psu
      idic(Y)(p11.32)/46,XY and haploinsufficiency of SHOX: A case report.
AB  - A male newborn presented with hypospadias and differential testicular volumes.
      Short femur length was detected four times during pregnancy, at 23, 31, 32 and 33
      weeks, by ultrasonographic examination. Chromosome analysis was performed on
      peripheral lymphocytes obtained from the infant and his parents. Fluorescent in
      situ hybridization (FISH), using sex determining region Y (SRY)/DXZ1 and DYZ3
      probes, was performed to verify the deletion of the SRY gene (located on Yp11.3
      region) and the activation of Y chromosomal centromeres. Single nucleotide
      polymorphism (SNP)-array comparative genomic hybridization (CGH) was used to
      detect copy number variations in the infant. The results revealed a ~2.2 Mb
      mircodeletion on Yp11.32 containing the short stature homeobox (SHOX) gene.
      According to the above examinations, the abnormal Y chromosome of the patient was
      identified as a dicentric derivate of the Y chromosome with pseudoinactivation of
      one of the two centromeres. The karyotype is therefore:
      45,X[20]/46,X,idic(Y)(p11.3).ish psu idic(Y)(p11.3) (SRY++, DYZ3++). array
      Yp11.32 (118,551-2,393,500)x0[26]/46,X,ishY(SRY+, DYZ3+)[4]. The combination of
      cytogenetic, FISH and SNP-array CGH technologies was beneficial for diagnosing
      the karyotype accurately, predicting the prognosis, and preparing an effective
      treatment plan for the patient.

PMID- 28498392
TI  - The flightless I protein interacts with RNA-binding proteins and is involved in
      the genome-wide mRNA post-transcriptional regulation in lung carcinoma cells.
AB  - The flightless I protein (FLII) belongs to the gelsolin family. Its function has
      been associated with actin remodeling, embryonic development, wound repair, and
      more recently with cancer. The structure of FLII is characterized by the N
      terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units
      that are both protein-protein inter-action domains, suggesting that FLII may
      exert its function by interaction with other proteins. Therefore, systematic
      study of protein interactions of FLII in cells is important for the understanding
      of FLII functions. In this study, we found that FLII was downregulated in lung
      carcinoma cell lines H1299 and A549 as compared with normal HBE (human bronchial
      epithelial) cell line. The investigation of FLII interactome in H1299 cells
      revealed that 74 of the total 132 putative FLII interactors are involved in RNA
      post-transcriptional modification and trafficking. Furthermore, by using high
      throughput transcriptome and translatome sequencing combined with cell
      fractionation, we showed that the overexpression or knockdown of FLII impacts on
      the overall nuclear export, and translation of mRNAs. IPA analysis revealed that
      the majority of these target mRNAs encode the proteins whose functions are
      reminiscent of those previously reported for FLII, suggesting that the post
      transcriptional regulation of mRNA might be a major mechanism of action for FLII.

PMID- 28498393
TI  - Upregulation of circadian gene 'hClock' contribution to metastasis of colorectal
      cancer.
AB  - Recent studies have shown that disruption of the circadian rhythm was one of the
      endogenous factors contributing to tumorigenesis of various human malignancies,
      including colorectal cancer (CRC). However, the roles of circadian genes in the
      development of CRC are still unexplored. In this study, we investigated the
      expression pattern and the underlying mechanism of human Clock gene (hClock) in
      CRC progression. Multiple methods such as qRT-PCR, immunohistochemistry, and
      western blotting were performed to evaluate the expression pattern of the gene
      hClock, as well as to observe the changes of angiogenesis-related proteins and
      EMT-related proteins. Transwell cell migration assays and an animal tumor
      metastasis model were used to examine the impact of hClock on the metastatic
      ability of CRC cells in vitro and in vivo. Our results showed that the expression
      level of hClock significantly increased in human CRC tissues, which strongly
      associated with late TNM stage and positive lymph node metastasis. Moreover, a
      higher level of hClock expression was found in CRC cell lines with a higher
      metastatic potential. Furthermore, ectopic expression of hClock promoted the
      migration of SW480 CRC cells, while knockdown of hClock inhibited the tumor
      metastasis of SW620 CRC cells, and targeting hClock by shRNA effectively
      suppressed the metastatic ability of SW620 CRC cells in nude mice. Finally, we
      found that overexpression of hClock enhanced the expression of angiogenesis
      related genes such as HIF-1alpha, ARNT and VEGF, and promoted epithelial
      mesenchymal (-like) transition (EMT) in CRC cells, both of which are considered
      to be critical for tumor progression. These findings suggest that upregulation of
      the circadian gene hClock plays an important role in metastasis of colorectal
      cancer.

PMID- 28498394
TI  - miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1.
AB  - Exposure to trauma is a potential contributor to anxiety; however, the molecular
      mechanisms responsible for trauma-induced anxiety require further clarification.
      In this study, in an aim to explore these mechanisms, we observed the changes in
      the hypothalamic pituitary adrenal (HPA) axis using a radioimmunoassay and the
      changes in anxiety-like behavior using the open field test and elevated plus maze
      test in a rat model following intervention with NBI-27914, a specific
      corticotropin-releasing hormone receptor 1 (CRHR1) antagonist. CRHR1 was found to
      be involved in trauma-induced anxiety. We then applied bioinformatic analysis to
      screen microRNAs (miRNAs or miRs) that target CRHR1, and miR-34b was determined
      to negatively regulate CRHR1 mRNA in primary hypothalamic neurons. The
      overexpression of miR-34b in the paraventricular nucleus (PVN) by a miRNA agomir
      using a drug delivery system decreased the hyperactivity of the HPA axis and
      anxiety-like behavior. Overall, the involvement of the HPA axis in trauma-induced
      anxiety was demonstrated, and trauma-induced anxiety was attenuated by decreasing
      the hyperactivity of the HPA axis via miR-34b by targeting CRHR1.

PMID- 28498395
TI  - MicroRNA-1299 is a negative regulator of STAT3 in colon cancer.
AB  - Signal transducers and activators of transcription (STAT) is a family of
      transcription factors which regulate cell proliferation, differentiation,
      apoptosis, metastasis, immune and inflammatory responses, and angiogenesis. STAT3
      is a latent cytoplasmic transcription factor that belongs to STATs. STAT3 has
      been reported be regulates genes involved with cellular growth, proliferation and
      metastasis. Worldwide, colon cancer is one of the leading causes of cancer
      related deaths. Cumulative evidence has established that STAT3 is essential for
      colon cancer progression to advanced malignancy. In our study, we showed that
      microRNA-1299 (miR-1299) was closely related to the TNM stage of colon cancer,
      and that the expression of miR-1299 was negatively correlated with the expression
      of STAT3 in colon cancer which means that miR-1299 can be a negative regulator of
      STAT3 in colon cancer. A total of 60 cases of different grades of colon samples
      were used to detect the expression of miR-1299. Results showed that miR-1299 was
      significantly lower in high-grade colons both in mRNA and protein levels.
      Furthermore, Overall survival (OS) in patients with low miR-1299 is shorter than
      25.6 months, as compared with an OS of 28.4 months in patients with high level of
      miR-1299. We also confirmed that the overexpression of miR-1299 can not only
      downregulate the STAT3 pathway, but also inhibited colon cancer cell growth. Our
      findings could provide new insights into the molecular therapeutic of colon
      cancer.

PMID- 28498396
TI  - Diverse expression patterns and tumorigenic role of neurotensin signaling
      components in colorectal cancer cells.
AB  - Colorectal cancer (CRC), which is one of the most common malignancies worldwide,
      results from an accumulation of genetic and epigenetic modifications including
      DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central
      nervous system, mediates its physiological and pathological effects, including
      growth stimulation for a variety of cancers, through three distinct NTS receptors
      (NTSRs). Most NTS functions are mediated through the high-affinity receptor
      NTSR1, and expression of NTSR1 is increased in many cancers including CRC. In
      this study, we investigated the expression profiles and cellular functions of the
      NTSRs, especially NTSR1, in CRC cells. We showed that expression levels for NTS
      and NTSR1 varied, that NTSR2 expression was not detectable and that NTSR3 was
      consistently expressed in all CRC cell lines examined. Treatment with the
      demethylating agent, 5-aza-2'-deoxycytidine, augmented levels of NTSR1/2 in Caco2
      and DLD1 cells, which have little or no transcripts for NTSR1/2 suggesting that
      DNA methylation suppresses NTSR1/2 expression. In addition, we demonstrated that
      knockdown of NTSR1 decreased cell growth and migration in HCT116 and HT29 cells.
      Finally, we showed that treatment with SR48692, an antagonist of NTSR1, also
      inhibited cell proliferation and migration in the CRC cells. Our findings
      identify promoter methylation as an important process regulating the differential
      expression or silencing of NTSR1/2 in CRC cells. Moreover, inhibition of NTSR1
      repressed tumorigenic effects in CRC cells, suggesting that NTSR1 may be used as
      a therapeutic target for CRC.

PMID- 28498397
TI  - Dihydroartemisinin inhibits the viability of cervical cancer cells by
      upregulating caveolin 1 and mitochondrial carrier homolog 2: Involvement of p53
      activation and NAD(P)H:quinone oxidoreductase 1 downregulation.
AB  - Dihydroartemisinin (DHA) has been shown to inhibit the viability of various
      cancer cells. Previous studies have revealed that the mechanisms involved in the
      inhibitory effects of DHA are based on theactivation of p53 and the mitochondrial
      related cell death pathway. However, the exact association between upstream
      signaling and the activation of cell death pathway remains unclear. In this
      study, we found that DHA treatment induced the upregulation of caveolin 1 (Cav1)
      and mitochondrial carrier homolog 2 (MTCH2) in HeLa cells, and this was
      associated with the DHA-induced inhibition of cell viability and DHA-induced
      apoptosis. Additionally, the overexpression of Cav1 and MTCH2 in HeLa cells
      enhanced the inhibitory effects of DHA on cell viability. Moreover, we also found
      that the upregulation of Cav1 contributed to the DHA-mediated p53 activation and
      the downregulation of the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1),
      which have been reported to contribute to the activation of the cell death
      pathway. Of note, we also found that DHA induced the nuclear translocation and
      accumulation of both Cav1 and p53, indicating a novel potential mechanism, namely
      the regulation of p53 activation by Cav1. On the whole, our study identified Cav1
      and MTCH2 as the molecular targets of DHA and revealed a new link between the
      upstream Cav1/MTCH2 upregulation and the downstream activation of the cell death
      pathway involved in the DHA-mediated inhibition of cell viability.

PMID- 28498398
TI  - PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in
      rheumatoid arthritis and is implicated in disease susceptibility.
AB  - The clinical symptoms of rheumatoid arthritis (RA) present with circadian
      variation, with joint stiffness and pain more prominent in the early morning. The
      mammalian clock genes, which include circadian locomotor output cycles kaput,
      brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian
      rhythms. In order to identify the association between genetic polymorphisms in
      the circadian clock gene period 2 (PER2) and RA, the present study genotyped
      three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and
      rs2304674, using genetic information from 256 RA patients and 499 control
      subjects. Primary cultured rheumatoid synovial cells were stimulated with 10 uM
      lipopolysaccharide (LPS). Total protein was then extracted from the synovial
      cells following 12 and 24 h, and PER2 protein expression was assayed by
      immunoblotting. The rs2304674 SNP demonstrated a significant association with
      susceptibility to RA following Bonferroni correction. However, statistical
      analysis indicated that the SNPs were not associated with any clinical features
      of patients with RA. Immunoblotting analysis demonstrated that PER2 protein
      expression was decreased by LPS-induced inflammation in RA synovial cells;
      however, this was not observed in normal synovial cells. The results suggest that
      the PER2 gene may be a risk factor for RA, and expression of the PER2 protein may
      be affected by inflammation. Therefore, PER2 may contribute to the pathogenesis
      of RA.

PMID- 28498399
TI  - Dual inhibition of IGF1R and ER enhances response to trastuzumab in HER2 positive
      breast cancer cells.
AB  - Although HER2 targeted therapies have improved prognosis for HER2 positive breast
      cancer, HER2 positive cancers which co-express ER have poorer response rates to
      standard HER2 targeted therapies, combined with chemotherapy, than HER2
      positive/ER negative breast cancer. Administration of hormone therapy
      concurrently with chemotherapy and HER2 targeted therapy is generally not
      recommended. Using publically available gene expression datasets we found that
      high expression of IGF1R is associated with shorter disease-free survival in
      patients whose tumors are ER positive and HER2 positive. IGF1R is frequently
      expressed in HER2 positive breast cancer and there is significant evidence for
      crosstalk between IGF1R and both HER2 and ER. Therefore, we evaluated the
      therapeutic potential of targeting ER and IGF1R in cell line models of
      HER2/ER/IGF1R positive breast cancer, using tamoxifen and two IGF1R targeted
      tyrosine kinase inhibitors (NVP-AEW541 and BMS-536924). Dual inhibition of ER and
      IGF1R enhanced growth inhibition in the four HER2 positive cell lines tested and
      caused an increase in cell cycle arrest in G1 in BT474 cells. In addition,
      combined treatment with trastuzumab, tamoxifen and either of the IGF1R TKIs
      enhanced response compared to dual targeting strategies in three of the four HER2
      positive breast cancer cell lines tested. Furthermore, in a cell line model of
      trastuzumab-resistant HER2 positive breast cancer (BT474/Tr), tamoxifen combined
      with an IGF1R TKI produced a similar enhanced response as observed in the
      parental BT474 cells suggesting that this combination may overcome acquired
      trastuzumab resistance in this model. Combining ER and IGF1R targeting with HER2
      targeted therapies may be an alternative to HER2 targeted therapy and
      chemotherapy for patients with HER2/ER/IGF1R positive breast cancer.

PMID- 28498400
TI  - TRIM28 knockdown increases sensitivity to etoposide by upregulating E2F1 in non
      small cell lung cancer.
AB  - Tripartite motif containing 28 (TRIM28) is a universal corepressor for Kruppel
      associated box zinc finger proteins. In our previous study, it was shown that
      expression of TRIM28 is upregulated in non-small cell lung cancer (NSCLC) cell
      lines and tissues. Here, we demonstrated that the stable silencing of TRIM28
      expression by a specific siRNA lentivirus vector increased the sensitivity of
      NSCLC cells to chemotherapeutic agent etoposide. Combination of TRIM28 siRNA and
      etoposide significantly inhibited the growth and proliferation of lung
      adenocarcinoma PAa cells and exerted obvious antitumor effects in nude mice.
      Using FCM and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end
      labeling (TUNEL) assay, we found that TRIM28 siRNA in combination with etoposide
      increased apoptosis in vitro and in vivo which was induced by E2F1 activity,
      since the expression of E2F1 and its target genes was significantly increased in
      the cotreatment group. Cell proliferation and apoptosis were almost completely
      abolished in the PAa cells cotreated with TRIM28 siRNA and etoposide following
      knockdown of E2F1. The results of our study demonstrated that the combination of
      TRIM28 siRNA and etoposide may be effective against NSCLC and has the potential
      of being a new therapeutic tool for future treatment.

PMID- 28498401
TI  - Luteolin-induced apoptosis through activation of endoplasmic reticulum stress
      sensors in pheochromocytoma cells.
AB  - Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active
      flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits
      tumor cell proliferation, inflammatory and oxidative stress better, when compared
      with other flavonoids. In the present study, it was demonstrated that luteolin
      induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the
      rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic
      bodies. In addition, luteolin regulates expression of the endoplasmic reticulum
      (ER) chaperone binding immunoglobulin protein, activating ER stress sensors
      (eukaryotic initiation factor 2alpha phosphorylation and X-box binding protein 1
      mRNA splicing) and induced autophagy. The results indicated that luteolin induces
      the upregulation of the unfolded protein response pathway through the ER stress
      sensors, which helps as an influential regulator for the apoptosis pathway in
      PC12 cells. The results suggested that the understanding of the molecular
      mechanisms underlying luteolin-induced apoptosis may be useful in cancer
      therapeutics, chemoprevention and neurodegenerative diseases, such as Parkinson's
      disease and Alzheimer's disease.

PMID- 28498402
TI  - Effects of RUNX3 mediated Notch signaling pathway on biological characteristics
      of colorectal cancer cells.
AB  - This study investigated the effects of runt-related transcription factor 3
      (RUNX3) mediated Notch pathway on the biological behavior of colorectal cancer
      (CRC) SW260 cells. CRC tissues and para-carcinoma tissues were collected from 182
      CRC patients who had undergone surgical treatment between January 2008 and
      December 2010. Immunohistochemical staining with streptavidin-peroxidase (SP) was
      used to detect RUNX3, Notch1 and Jagged 1 expression levels. CRC SW260 cells were
      divided into the following groups: Control group, si-NC group, si-RUNX3 group,
      DAPT group, si-RUNX3+DAPT group, and si-NC+DAPT group. Expression levels of
      RUNX3, and Notch signaling related genes were measured by real-time fluorescence
      quantitative polymerase chain reaction (RT-qPCR) and western blotting in vitro.
      Besides, MTT, soft agar colony formation, Annexin V-FITC/PI double staining and
      Transwell were performed to analyze the effects of RUNX3 on cell growth and
      metastasis. Lower positive expression rate of RUNX3 and higher positive
      expression rate of Notch1 and Jagged 1 were observed in CRC tissues than those in
      normal adjacent tissues with a negative correlation, and the expression levels
      were associated with the differentiation degree, TNM staging, lymph node
      metastasis and tumor invasion depth (all P<0.05). RUNX3 expression was reduced in
      si-RUNX3 and si-RUNX3+DAPT group but the expression levels of Notch signaling
      related genes were markedly increased in si-RUNX3 group or decreased in DAPT and
      si-NC+DAPT group, as compared with those in the control group (all P<0.05). In
      addition, the proliferation, colony formation, migration and invasion abilities
      of SW260 cells were enhanced in si-RUNX3 group but were restricted in DAPT and si
      NC+DAPT group, which was contrary to cell apoptosis (all P<0.05). RUNX3
      contributes to attenuate the proliferation and metastasis of CRC cells, and
      promotes cell apoptosis through inhibition of Notch signaling pathway.

PMID- 28498403
TI  - Mus musculus-microRNA-449a ameliorates neuropathic pain by decreasing the level
      of KCNMA1 and TRPA1, and increasing the level of TPTE.
AB  - Neuropathic pain is a nerve disorder characterized by the dysregulation of ion
      channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be
      associated with the molecular mechanisms underlying the altered levels of ion
      channels; however, the molecular mechanisms remain widely unknown. To investigate
      these mechanisms, the present study conducted a genomic analysis of miR between a
      unilateral spared nerve injury (SNI) model and sham control. Differentially
      expressed miRs between the SNI and sham groups were selected for transfection of
      DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently
      performed. A total of three significantly differently expressed genes were
      selected from the results of the PCR array and further analyzed by reverse
      transcription-quantitative PCR. Genomic analysis revealed that Mus musculus miR
      449a (mmu-miR-449a) was reduced in the SNI groups compared with the sham
      controls. The PCR array indicated that mmu-miR-449a-transfection reduced the mRNA
      expression levels of transient receptor potential cation channel subfamily A
      member 1 (TRPA1), and calcium-activated potassium channel subunit alpha-1
      (KCNMA1) and increased the level of transmembrane phosphatase with tension
      homology (TPTE) in the DRG cells (P<0.05). qRT-PCR analysis further indicated
      that mmu-miR-449a transfection caused similar alterations in the mRNA expression
      levels of TRPA1, KCNMA1 and TPTE in DRG cells, respectively (P<0.05). Therefore,
      mmu-miR-449a may ameliorate neuropathic pain by decreasing the activity of the
      channel proteins TRPA1 and KCNMA1 and increasing the levels of TPTE. mmu-miR-449a
      may be a potential therapeutic molecule for the alleviation of neuropathic pain.

PMID- 28498404
TI  - Methylation modification in gastric cancer and approaches to targeted epigenetic
      therapy (Review).
AB  - Gastric cancer (GC) is one of the most common cancers and the second leading
      cause of cancer-related mortality. Increasing discoveries have highlighted
      aberrant epigetic modifications actively contribute to the pathogenesis of this
      fatal disease. Among these epigenetic events, dysregulated methylation is
      particularly associated with GC progression. Importantly, these aberrant
      methylation modifications caused by the misregulation of methyltranferases are
      frequently reversible, which provides opportunities for targeted treatment using
      specific molecular inhibitors. In the present review, we provide an overview of
      the current literature on the changes of DNA and histone methylations that alter
      gene expressions in GC and describe the emerging targeted epigenetic therapy in
      GC.

PMID- 28498405
TI  - Application of metabolomics: Focus on the quantification of organic acids in
      healthy adults.
AB  - Metabolomics, a 'budding' discipline, may accurately reflect a specific phenotype
      which is sensitive to genetic and epigenetic interactions. This rapidly evolving
      field in science has been proposed as a tool for the evaluation of the effects of
      epigenetic factors, such as nutrition, environment, drug and lifestyle on
      phenotype. Urine, being sterile, is easy to obtain and as it contains metabolized
      or non-metabolized products, is a favored study material in the field of
      metabolomics. Urine organic acids (OAs) reflect the activity of main metabolic
      pathways and have been used to assess health status, nutritional status, vitamin
      deficiencies and response to xenobiotics. To date, a limited number of studies
      have been performed which actually define reference OA values in a healthy
      population and as reference range for epigenetic influences, and not as a
      reference to congenital metabolic diseases. The aim of the present study was thus
      the determination of reference values (RVs) for urine OA in a healthy adult
      population. Targeted metabolomics analysis of 22 OAs in the urine of 122 healthy
      adults by gas chromatography-mass spectrometry, was conducted. Percentile
      distributions of the OA concentrations in urine, as a base for determining the
      RVs in the respective population sample, were used. No significant differences
      were detected between female and male individuals. These findings can facilitate
      the more sensitive determination of OAs in pathological conditions. Therefore,
      the findings of this study may contribute or add to the information already
      available on urine metabolite databases, and may thus promote the use of targeted
      metabolomics for the evaluation of OAs in a clinical setting and for
      pathophysiological evaluation. However, further studies with well-defined
      patients groups exhibiting specific symptoms or diseases are warranted in order
      to discern between normal and pathological values.

PMID- 28498406
TI  - Crizotinib, a MET inhibitor, prevents peritoneal dissemination in pancreatic
      cancer.
AB  - Peritoneal dissemination is a frequent occurrence in pancreatic cancer, which is
      associated with a poor prognosis. MET is associated with the progression of
      pancreatic cancer; therefore, we evaluated the effect of a MET inhibitor,
      crizotinib, on peritoneal dissemination of pancreatic cancer. Crizotinib
      inhibited the growth of 8 pancreatic cancer cell lines with the IC50 ranging from
      1.4 to 4.3 uM. Invasion of the pancreatic cancer cell line Suit-2, was suppressed
      in vitro at a concentration of 1.0 uM, which is sufficient for the inhibition of
      MET phosphorylation. This effect on cell invasion was also recapitulated by the
      reduction of MET expression in Suit-2 with siRNA. Crizotinib also inhibited RhoA
      activation in addition to MET phosphorylation. We further evaluated the effect of
      crizotinib on peritoneal dissemination of pancreatic cancer in vivo. Crizotinib
      reduced tumor burden and ascites accumulation due to development of peritoneal
      dissemination after inoculation of Suit-2. Taken together, crizotinib may be a
      potent drug for treating peritoneal dissemination of pancreatic cancer by
      inhibiting cancer cell proliferation and invasion, at least in part through the
      suppression of HGF/MET signaling and RhoA activation.

PMID- 28498407
TI  - Respiratory syncytial virus infection accelerates lung fibrosis through the
      unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model.
AB  - Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is
      involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the
      underlying mechanism remains unclear. Viral infection often triggers a
      hyperinflammatory response by an expansion of the ER. The present study was
      designed to observe the role of respiratory syncytial virus infection (RSV)
      induced ER stress on lung fibrosis. In order to determine the role of ER stress
      on the onset and progression of pulmonary fibrosis, mice received an
      intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and
      21 following combined injection, RSV in the lung tissues was assayed by
      immunohistochemistry, cellular classification was assayed by direct microscopic
      observation after Wright staining and the secretion of cytokines in the broncho
      alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen
      type I was assayed by immunofluorescence and western blot analysis. The
      expression of ER stress related proteins was analyzed by western blot. In
      addition, the correlations of ER-stress related proteins with collagen type-1
      were examined. RSV administration resulted in increased inflammation, as
      demonstrated by increased levels of leukocytes and pro-inflammatory cytokines in
      the BALF, and increased collagen type-1 deposition in the lung tissues of
      bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV
      promoted the expression of phosphorylated protein kinase R-like endoplasmic
      reticulum kinase (p-PERK), 78 kDa glucose-regulated protein (GRP78) and
      activating transcription factor 6alpha (ATF6alpha), which accelerated the
      severity and process of fibrosis in bleomycin-induced animal models. The present
      study provides evidence that RSV infection accelerated the unfolded protein
      response and bleomycin-induced lung fibrosis, which may improve our understanding
      of the pathogenesis of pulmonary fibrosis.

PMID- 28498408
TI  - Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos
      exposure.
AB  - We have previously reported that chronic, recurrent and low-dose exposure to
      asbestos fibers causes a reduction in antitumor immunity. Investigation of
      natural killer (NK) cells using an in vitro cell line model and comprising in
      vitro activation using freshly isolated NK cells co-cultured with chrysotile
      fibers, as well as NK cells derived from asbestos-exposed patients with pleural
      plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK
      cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro
      differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes
      (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules
      such as granzyme B and perforin, as well as suppressed proliferation of CTLs.
      Additionally, analysis of T helper cells showed that surface CXCR3, chemokine
      receptor, and the productive potential of interferon (IFN)gamma were reduced
      following asbestos exposure in an in vitro cell line model and in peripheral CD4+
      cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos
      exposure enhanced regulatory T cell (Treg) function. This study also focused on
      CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell
      receptor and co-culture with various concentrations of chrysotile fibers using
      freshly isolated CD4+ surface CXCR3 positive and negative fractions, the
      intracellular expression of CXCR3, IFNgamma and IL-17 remained unchanged when co
      cultured with chrysotile. However, subsequent re-stimulation with phorbol 12
      myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production
      and expression, particularly in CD4+ surface CXCR3 positive cells. These results
      indicated that the balance and polarization between Treg and Th-17 fractions play
      an important role with respect to the immunological effects of asbestos and the
      associated reduction in antitumor immunity.

PMID- 28498410
TI  - Neuropeptide Y suppresses epileptiform discharges by regulating AMPA receptor
      GluR2 subunit in rat hippocampal neurons.
AB  - The present study aimed to investigate the effects of neuropeptide Y (NPY) on the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      glutamate receptor 2 (GluR2) subunit in epileptiform discharge hippocampal
      neurons. Hippocampal neurons were harvested from neonatal Sprague-Dawley rats
      aged <24 h and primarily cultured in vitro. At day 12 following culture,
      hippocampal neurons were divided into the following groups: Control, Mg2+-free,
      NPY+Mg2+-free and BIBP3226+NPY+Mg2+-free. The action potential of neurons was
      measured using the whole cell patch clamp technique in the control, Mg2+-free and
      NPY+Mg2+-free groups. AMPA current (IAMPA) was detected and peak current density
      was calculated in each group. Alterations in total protein and phosphorylation of
      the GluR2 subunit were detected by western blot analysis, and GluR2 mRNA
      expression levels were detected by reverse transcription-quantitative polymerase
      chain reaction, in each group. The whole cell patch clamp technique demonstrated
      an abnormal action potential in the Mg2+-free group. The frequency and amplitude
      of the action potential were significantly greater in the Mg2+-free group
      compared with the control group, and significantly reduced in the NPY+Mg2+-free
      group compared with the Mg2+-free group (P<0.05). In the Mg2+-free group,
      compared with the control group, peak current density was significantly reduced
      (P<0.05), GluR2 subunit protein content was slightly reduced (P>0.05),
      phosphorylation levels of GluR2 subunit were significantly greater (P<0.05) and
      GluR2 mRNA was significantly reduced (P<0.05). In the NPY+Mg2+-free group,
      compared with the Mg2+-free group, peak current density was significantly greater
      (P<0.05), phosphorylation levels of GluR2 subunit were significantly reduced
      (P<0.05) and GluR2 mRNA expression was significantly greater (P<0.05). In the
      BIBP3226+NPY+Mg2+-free group, compared with the NPY+Mg2+-free group, peak current
      density was significantly reduced (P<0.05), phosphorylation levels of GluR2
      subunit were significantly greater (P<0.05) and GluR2 mRNA expression was
      significantly reduced (P<0.05). After 3 h of treatment with Mg2+-free
      extracellular fluid, epileptiform discharge was detected in the cells. NPY
      inhibited the discharge and its underlying mechanism may be that epileptiform
      discharge suppressed the function of the AMPA receptor GluR2 subunit. NPY
      relieved the inhibition of the GluR2 subunit via the Y1 receptor. This may
      provide a novel direction for future studies on the pathogenesis and treatment of
      epilepsy.

PMID- 28498409
TI  - Demonstration of a potent RET transcriptional inhibitor for the treatment of
      medullary thyroid carcinoma based on an ellipticine derivative.
AB  - Dominant-activating mutations in the RET (rearranged during transfection) proto
      oncogene, which encodes a receptor tyrosine kinase, is often associated with the
      development of medullary thyroid carcinoma (MTC). The proximal promoter region of
      the RET gene consists of a guanine-rich sequence containing five runs of three
      consecutive guanine residues that serve as the binding site for transcriptional
      factors. As we have recently shown, this stretch of nucleotides in the promoter
      region is highly dynamic in nature and tend to form non-B DNA secondary
      structures called G-quadruplexes, which suppress the transcription of the RET
      gene. In the present study, ellipticine and its derivatives were identified as
      excellent RET G-quadruplex stabilizing agents. Circular dichroism (CD)
      spectroscopic studies revealed that the incorporation of a piperidine ring in an
      ellipticine derivative, NSC311153 improves its binding with the G-quadruplex
      structure and the stability induced by this compound is more potent than
      ellipticine. Furthermore, this compound also interfered with the transcriptional
      mechanism of the RET gene in an MTC derived cell line, TT cells and significantly
      decreased the endogenous RET protein expression. We demonstrated the specificity
      of NSC311153 by using papillary thyroid carcinoma (PTC) cells, the TPC1 cell line
      which lacks the G-quadruplex forming sequence in the promoter region due to
      chromosomal rearrangement. The RET downregulation selectively suppresses cell
      proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR
      signaling pathways in the TT cells. In the present study, we also showed that the
      systemic administration of a water soluble NSC311153 analog in a mouse MTC
      xenograft model inhibited the tumor growth through RET downregulation.

PMID- 28498411
TI  - Mitochondrial activity and oxidative stress functions are influenced by the
      activation of AhR-induced CYP1A1 overexpression in cardiomyocytes.
AB  - There is an endemic cardiomyopathy currently occurring in China, termed, Keshan
      disease (KD). The authors previously compared mitochondrial-associated gene
      expression profiles of peripheral blood mononuclear cells (PBMCs) derived from KD
      patients and normal controls, using mitochondria-focused cDNA microarray
      technology. The results detected an upregulation of the enzyme-associated CYP1A1
      gene, (ratios >=2.0). The aryl hydrocarbon receptor (AhR) regulates the
      expression of numerous cytochrome P450 (CYP) genes including members of the CYP1
      family; CYP1A1 and CYP1A2. Several previous studies have suggested roles for the
      aryl hydrocarbon receptor (AhR) and the genes that it regulates. An example
      involves cytochrome P4501A1 (CYP1A1), in the pathogenesis of heart failure,
      cardiac hypertrophy and other cardiomyopathies. Mitochondria comprise ~30% of the
      intracellular volume in mammalian cardiomyocytes, and subtle alterations in
      mitochondria can markedly influence cardiomyopathies. The present study
      investigated alterations in the activity and functions of mitochondria following
      AhR-induced overexpression of CYP1A1. AC16 cells were treated with the CYP1A1
      inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and cytotoxicity was then
      evaluated in MTT assays. Reverse transcription-quantitative polymerase chain
      reactions, western blot analysis and 7-ethoxyresorufin O-deacylase assays were
      performed to analyze the mRNA and protein levels, and the enzymatic activity of
      CYP1A1. Mitochondrial activity and mass were analyzed using an inverted
      fluorescence microscope and a fluorescence microplate reader. Reactive oxygen
      species (ROS) activity was analyzed using flow cytometry. The results of the
      current study demonstrated that TCDD gradually increased mRNA and protein levels
      of AhR and CYP1A1, in addition to the enzymatic activity. Mitochondrial activity
      and the quality of mitochondrial membranes were also significantly attenuated,
      and mitochondrial ROS levels were elevated in the TCDD-induced cardiomyocytes.
      The results indicate the involvement of the AhR/CYP1A1 signaling pathway in the
      mechanism of action of TCDD in human cardiomyocytes. The present findings may
      provide an explanation for myocardial injuries caused by polycyclic aromatic
      hydrocarbons. The authors conclude that exposure to TCDD results in regulatory
      alteration to the expression of detoxification genes that ultimately affect the
      metabolic activation and function of cardiomyocytes.

PMID- 28498412
TI  - Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with
      fibroblasts.
AB  - Emmprin (extracellular matrix metalloproteinase inducer, CD147) is a glycosylated
      transmembrane protein, consisting of two immunoglobulin domains, that stimulates
      the production of matrix metalloproteinases (MMPs) by tumor-associated
      fibroblasts. These effects play important roles in tumor invasion and metastasis.
      However, the precise mechanisms by which emmprin acts on fibroblasts have not
      been fully elucidated, especially in sarcoma cells. Previously, we demonstrated
      that emmprin, expressed in conditioned medium collected from the epithelioid
      sarcoma cell line (FU-EPS-1), stimulates MMP-2 production via interactions with
      fibroblasts. In this study, we used microvesicles derived from sarcoma cells, and
      determined whether emmprin exists in the microvesicles, which enhance the
      production of MMP-2 via fibroblasts. Microvesicles released from FU-EPS-1 cells
      were shown to contain full-length emmprin, identified as a 45-kDa protein
      characterized by polylactosamine glycosylation. Microvesicles collected from FU
      EPS-1 cells transfected with emmprin-specific siRNA or transduced with shRNA
      displayed significantly reduced MMP-2 production by fibroblasts compared with
      those from control-transfected cells. Our findings show that emmprin is released
      through microvesicle shedding in sarcoma cells, and emmprin in microvesicles
      regulates MMP-2 production by influencing the activity of fibroblasts located at
      sites distant from the tumor cells.

PMID- 28498413
TI  - CpG oligodeoxynucleotides augment antitumor efficacy of folate receptor alpha
      based DNA vaccine.
AB  - Folate receptor alpha (FRalpha) is overexpressed in a variety of solid tumors and
      has become an attractive target antigen for immunotherapy purposes. A DNA vaccine
      was generated by ligation of FRalpha cDNA into the eukaryotic vector pcDNA3.1.
      Expression of FRalpha was confirmed in transiently transfected B16 cells. B16
      cell lines that stably express FRalpha were set up by G418 selection. A total of
      100 ug purified plasmid DNA alone or in combination with CpG
      oligodeoxynucleotides (CpG ODN) was injected intramuscularly in C57BL/6 mice four
      times at one week intervals. ELISA analysis confirmed that high titers of
      antibodies against FRalpha existed in the sera of the experimental animals.
      Specific cytotoxic T lymphocyte activity against FRalpha-expressing B16 cells was
      found and FRalpha specific lymphocyte proliferation was detected. Coinjection of
      CpG ODN increased both humoral and cellular immune responses. In the protective
      model, in which C57BL/6 mice were immunized with the FRalpha DNA vaccine four
      weeks before tumor cell inoculation, the growth of tumor was significantly
      inhibited, and the presence of CpG ODN further increased the inhibitory effect.
      FRalpha DNA vaccine alone did not show a significant inhibitory effect in the
      therapeutic model, in which the DNA vaccine was immediately injected after tumor
      inoculation. However, FRalpha DNA vaccine plus CpG ODN showed a significant
      inhibitory effect in tumor growth. Survival curves for both animal experiments
      confirmed that mice immunized with pcDNA3.1/FRalpha plus CpG ODN had a
      significantly prolonged survival period than that of the pcDNA3.1 control group,
      the CpG ODN group or the pcDNA3.1/FRalpha group. The above showed that human
      FRalpha based DNA vaccination with CpG ODN as an adjuvant was effective in growth
      inhibition of a FRalpha expressing tumor in mice and deserves further evaluation
      as a possible immunotherapy.

PMID- 28498414
TI  - Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with
      orthotopically-implanted hepatocarcinoma.
AB  - Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor
      prognosis and high mortality. At present, vaccination with tumor cell lysate
      (TCL) loaded dendritic cells (DC) has been shown to be an effective therapy
      against HCC. However, the ability of promoting the specific T cell immune
      response is rather weak, influencing the antitumor response. Thus, it is
      necessary to find a strategy to improve the antitumor effect of TCL-loaded DC.
      Activation of signal transducer and activator of transcription 3 (STAT3)
      significantly inhibits antitumor immune response and DC maturity. Nifuroxazide,
      an antidiarrheal agent, has been proved to directly inhibit STAT3 activation.
      Thus, we investigated whether nifuroxazide could improve the antitumor immune
      response in mice vaccinated with TCL-loaded DC. The study provides the
      theoretical and experimental basis for developing an effective adjuvant for DC
      vaccine to treat HCC. Our results showed that the administration of nifuroxazide
      and DC-loaded TCL could significantly improve the survival rate, inhibit the
      tumor growth, and prompt the antitumor immune responses in mice with
      orthotopically implanted hepatocarcinomas, thus, possibly providing a new
      combination strategy to treat HCC.

PMID- 28498416
TI  - Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast
      cancer by estrogen receptor status and its clinical significance.
AB  - The lipid metabolic enzymes are considered candidate therapeutic targets for
      breast cancer. Long-chain acyl-coenzyme A (CoA) synthase (ACSL) is one of lipid
      metabolic enzymes and converts free-fatty acid to fatty acid-CoA. Five ACSL
      isoforms including ACSL1, ACSL3, ACSL4, ACSL5 and ACSL6 are identified in human.
      High ACSL4 expression has been observed in aggressive breast cancer phenotype.
      However, the role of other isoforms is still little-known. We therefore, analyzed
      the expression of ACSL isoforms in each subtype of breast cancer within METABRIC
      dataset and cancer cell line encyclopedia dataset. The expression levels of
      ACSL1, ACSL4 and ACSL5 in estrogen receptor (ER)-negative group were higher than
      that in ER-positive group. Similar expression pattern was detected among breast
      cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Treatment of
      ACSL inhibitor triacsin C which inhibited enzyme activity of ACSL 1, 3, 4 and 5
      suppressed cell growth of MCF-7 and MDA-MB-231. Our results further showed that
      high ACSL5 expression was associated with good prognosis in patients with both ER
      positive and ER-negative breast cancer through KM plotter analysis. These results
      suggest that ACSL1, ACSL4 and ACSL5 expression is regulated by ER signaling
      pathways and ACSL5 is a potential novel biomarker for predicting prognosis of
      breast cancer patients.

PMID- 28498415
TI  - Downregulated connexin32 promotes EMT through the Wnt/beta-catenin pathway by
      targeting Snail expression in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the common malignances in the world and
      is associated with high mortality and poor prognosis, partly due to early
      invasion and metastasis. Cx32 has been indicated to be involved in the
      progression of many cancers including HCC, but its relationship with tumor
      invasion and metastasis is still controversial. In the present study, the
      downregulated Cx32 in HCC tissue was found negatively correlated with
      histological grade and lymph node metastasis. Cx32 regulated HCC migration and
      invasion in vitro and inhibited tumor metastasis in xenograft models in vivo. We
      subsequently identified that Cx32 mediated epithelial-mesenchymal transition
      (EMT) by regulating Snail expression, and the enhanced Snail was due to
      activation of Wnt/beta-catenin signaling in response to Cx32 inhibition. Finally,
      decreased expression of Cx32 showed strong correlation with loss/reduction of E
      cadherin, higher expression of Snail, and nuclear accumulation of beta-catenin in
      HCC tissues. Taken together, our results suggest that Cx32 inhibits HCC invasion
      and metastasis through Snail-mediated EMT, Cx32 and this signaling pathway
      molecules may offer potential targets for HCC cancer therapy.

PMID- 28498417
TI  - CENP-H regulates the cell growth of human hepatocellular carcinoma cells through
      the mitochondrial apoptotic pathway.
AB  - The genomic alterations of hepatocellular carcinoma (HCC) are still unclear.
      Centromere protein-H (CENP-H) has been shown to be associated with many solid
      tumors. Our previous study found that CENP-H was upregulated in HCC and was
      related to patient prognosis. However, the biological functions of CENP-H in HCC
      and the possible underlying mechanisms have not been well elucidated. In the
      present study, we demonstrated that CENP-H knockdown inhibited the proliferation
      of Hep3B cells and decreased colony formation ability of single cells in vitro.
      Furthermore, CENP-H knockdown induced Hep3B cell apoptosis, and apoptotic bodies
      were observed using transmission electron microscopy. The protein expression of
      cleaved caspase-3 was upregulated in Hep3B cells after CENP-H knockdown.
      Additionally, a Bax/Bcl-2 ratio imbalance with a significant increase of Bax and
      a substantial decrease of Bcl-2 at both the mRNA and protein levels were
      determined in this study. In an animal experiment, CENP-H knockdown blocked the
      growth of Hep3B subcutaneous xenografts. Immunohistochemistry revealed that the
      protein expression of cleaved caspase-3 and Bax was increased, whereas the
      protein expression of Bcl-2 and Ki-67 was decreased in subcutaneous xenografts of
      the CENP-H-knockdown group. In summary, CENP-H may be involved in cell
      proliferation and apoptosis of HCC cells through the mitochondrial apoptotic
      pathway. Combined with previous studies, the data provide a new perspective on
      HCC development and progression.

PMID- 28498418
TI  - Identification and expression of MMSA-8, and its clinical significance in
      multiple myeloma.
AB  - In our previous studies, we identified 12 multiple myeloma (MM)-associated
      antigens by serological analysis of tumor-associated antigens with a recombinant
      cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one
      of the new antigens identified. We determined the 3'- and 5'-ends of MMSA-8 using
      SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length
      cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A
      related transcript variant 1 that is specifically associated with MM. We examined
      its prognostic significance for the first time, by investigating the correlations
      between MMSA-8 expression and definite clinicopathological features. We
      quantitatively assessed MMSA-8 expression using qRT-PCR and western blot analysis
      in healthy donors and MM patients. The expression levels of MMSA-8 were
      upregulated with statistical significance in MM patients in contrast to those in
      healthy donors. The expression of MMSA-8 was also upregulated in relapsed
      patients compared with that in the complete remission (CR) group. Contrasting
      MMSA-8 expression levels in different patients with definite clinicopathological
      features suggested an association between MMSA-8 with unfavorable
      clinicopathological characteristics, such as international staging system (ISS)
      stage III, higher lactate dehydrogenase (LDH) levels and higher C-reactive
      protein (CRP) levels. The expression of MMSA-8 was also increased in patients
      with unfavorable cytogenetic and genetic abnormalities, including the presence of
      t(11;14), t(4;14), t(14;16), del(17p), del(13q) and p53 deletion, which was
      statistically significant. The expression of MMSA-8 exhibited significant
      variance in the treatment responses of the CR, PR, progression and relapse
      groups. Univariate and multivariate analyses revealed that high MMSA-8 values
      were associated with poorer progression-free survival (PFS) and overall survival
      (OS) in MM patients independently. In conclusion, our data indicated that MMSA-8
      is an independent and unfavorable prognostic risk factor in MM; MMSA-8 is also a
      promising diagnostic and therapeutic target in MM patients, but further
      validation is needed.

PMID- 28498420
TI  - CRISPR/Cas9-mediated genome engineering of CXCR4 decreases the malignancy of
      hepatocellular carcinoma cells in vitro and in vivo.
AB  - CXC chemokine receptor 4 (CXCR4) is associated with poor clinical outcomes and
      decreased survival in hepatocellular carcinoma (HCC). In the present study, we
      targeted CXCR4 by CRISPR/Cas9 in HepG2 cells and observed the effects both in
      vitro and in vivo. The results indicated that after targeting CXCR4 the
      expression of CXCR4 was significantly decreased and the cell proliferation was
      inhibited. Clonogenicity and scratch cell migration assays indicated that
      specific downregulation of CXCR4 inhibited cell migration. This disruption of
      CXCR4 led to less invasiveness, the genes related to epithelial-mesenchymal
      transition (EMT) and cell self-renewal were also affected. Moreover, sensitivity
      to the anticancer drug cisplatin was significantly increased in vitro by the
      downregulation of CXCR4. The results of the in vivo study showed that the growth
      volumes were significantly smaller in neoplasms derived from CXCR4-downregulated
      HepG2 cells compared to those derived from wild-type cells. These results showed
      that targeting CXCR4 by CRISPR/Cas9 could inhibit proliferation, migration and
      invasion, reversed EMT, increased chemosensitivity and decrease the malignancy of
      HCC in vitro and in vivo.

PMID- 28498419
TI  - miR-590 regulates WT1 during proliferation of G401 cells.
AB  - Nephroblastoma (Wilms' tumor) is frequently associated with mortality in
      children. MicroRNAs (miRNAs) are important for tumor development serving as
      oncogenes or tumor suppressors. In the present study, miRNA-590 (miR-590) was
      identified to be upregulated in Wilms' tumor tissues compared with the normal
      adjacent tissues. Additionally, the levels of miR-590 were consistent with their
      clinical stage. Wilms' tumor 1 (WT1) was considered to be a tumor suppressor in
      certain tumor types, and it has been detected at low expression levels in various
      types of cancer with high cell proliferation and aggressive behavior. The
      expression levels of miR-590 were quantified using reverse transcription
      quantitative polymerase chain reaction. Cell proliferation was measured using 5
      ethynyl-20-deoxyuridine assays. The protein expression levels of WT1 were
      investigated by western blot analysis. To the best of our knowledge, the present
      study was the first to determine that WT1 was a target gene of miR-590 as miR-590
      was able to negatively regulate WT1 expression level by binding to the specific
      target site within the 3'-untranslated region (3'-UTR) of WT1 in G401 cells.
      Additionally, overexpression of miR-590 promoted G401 cell proliferation which
      was consistent with the effect of small interfering RNA-WT1. Subsequently, the
      present study determined that the cell phenotype altered by miR-590
      overexpression may be reversed by upregulation of WT1 in G401 cells. In
      conclusion, the observations indicated that miR-590 may function as an oncogene
      via targeting WT1 to induce G401 cell proliferation. These results may contribute
      to current understanding of the function of miR-590 in nephroblastoma.

PMID- 28498421
TI  - Molecular analysis of the mouse brain exposed to chronic mild stress: The
      influence of hepatocyte nuclear factor 4alpha on physiological homeostasis.
AB  - Major depressive disorder (MDD) is a prevalent disorder that causes considerable
      disability in social functioning and is a risk factor for physical diseases.
      Recent clinical reports have demonstrated a marked association between MDD and
      physiological dyshomeostasis induced by metabolic disorders, including diabetes,
      hormone abnormalities and autoimmune diseases. The authors of the present study
      have previously analyzed comparative gene expression profiles in the prefrontal
      cortex (PFC) of a chronic mild stress (CMS) animal model of MDD. Hepatocyte
      nuclear factor 4alpha (Hnf4alpha) was identified as a central regulator that
      exerted significant influence on genes associated with physiological homeostasis.
      The aim of the present study was to investigate: i) the molecular mechanism of
      the depressive state in the PFC, and ii) the involvement of genes extracted from
      the comparative gene expression profiles, particularly those applicable to MDD in
      clinical practice. Core analysis of the previous PFC microarray results was
      performed using Ingenuity Pathway Analysis (IPA). Subsequently, IPA was used to
      search for molecules that are regulated by Hnf4alpha, and exist in the PFC and
      serum. From the core analysis, 5 genes that are associated with cell death and
      are expressed in the cortex were selected. Four of the extracted genes, insulin
      like growth factor 1, transthyretin, serpin family A member 3 and plasminogen,
      were markedly affected by Hnf4alpha. S100 calcium-binding protein A9 (S100a9) and
      alpha2-HS-glycoprotein (Ahsg) were also chosen as they exist in serum and are
      also affected by Hnf4alpha. A significant group difference in the expression of
      these two genes was detected in the PFC, thalamus and hippocampus. The protein
      levels of AHSG and S100A9 in the PFC and hippocampus of the CMS group increased
      significantly when compared with the control group. These findings support the
      close association of Hnf4alpha (through genes such as S100a9 and Ahsg) with the
      development of various diseases induced by deregulation of physiological
      homeostasis during the progression of MDD.

PMID- 28498422
TI  - Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer
      cell xenograft model, tissue microarray, and gene network analysis.
AB  - There is a growing interest in the use of naturally occurring agents in cancer
      prevention. This study investigated the garlic extract affects in bladder cancer
      (BC) prevention. The effect of garlic extract in cancer prevention was evaluated
      using the T24 BC BALB/C-nude mouse xenograft model. Microarray analysis of
      tissues was performed to identify differences in gene expression between garlic
      extract intake and control diet, and gene network analysis was performed to
      assess candidate mechanisms of action. Furthermore, we investigated the
      expression value of selected genes in the data of 165 BC patients. Compared to
      the control group, significant differences in tumor volume and tumor weight were
      observed in the groups fed 20 mg/kg (p<0.05), 200 mg/kg, and 1000 mg/kg of garlic
      extract (p<0.01). Genes (645) were identified as cancer prevention-related genes
      (fold change >2 and p<0.05) by tissue microarray analysis. A gene network
      analysis of 279 of these genes (p<0.01) was performed using Cytoscape/ClueGo
      software: 36 genes and 37 gene ontologies were mapped to gene networks. Protein
      kinase A (PKA) signaling pathway including AKAP12, RDX, and RAB13 genes were
      identified as potential mechanisms for the activity of garlic extract in cancer
      prevention. In BC patients, AKAP12 and RDX were decreased but, RAB13 was
      increased. Oral garlic extract has strong cancer prevention activity in vivo and
      an acceptable safety profile. PKA signaling process, especially increasing AKAP12
      and RDX and decreasing RAB13, are candidate pathways that may mediate this
      prevention effect.

PMID- 28498423
TI  - PCDH10 gene inhibits cell proliferation and induces cell apoptosis by inhibiting
      the PI3K/Akt signaling pathway in hepatocellular carcinoma cells.
AB  - Protocadherin10 (PCDH10), a member of the non-clustered protocadherin (PCDH)
      family, functions as a tumor-suppressor gene in many cancers. Previous studies
      have demonstrated that the expression of PCDH10 was noticeably downregulated in
      the tissue and cells of hepatocellular carcinoma (HCC), when compared to those in
      normal liver tissue. The decreased PCDH10 expression in HCC was correlated with
      the aberrant methylation status of PCDH10 promoter. However, the biological
      functions and molecular mechanism of PCDH10 in HCC have yet to be elucidated. The
      aim of the present study was to identify the biological function and mechanisms
      of PCDH10 in HCC. Quantitative real-time polymerase chain reaction was used to
      detect the expression of PCDH10 in HCC cells with decreased expression of PCDH10
      which were transfected with plasmid pcDNA3.1-PCDH10 or pcDNA3.1-vector using
      Lipofectamine 2000. The biological effects of PCDH10 in HCC cells were detected
      by CCK-8, colony formation and flow cytometric assays. Western blot and co
      immunoprecipitation (Co-IP) assays were performed to explore the mechanism of
      PCDH10 in HCC cells. PCDH10 expression was downregulated in the HCC cells (HepG2,
      HuH7, HuH1, and SNU387) when compared to the normal liver cells (L02).
      Upregulation of PCDH10 inhibited cell proliferation and induced cell apoptosis in
      the HCC cells. More importantly, we revealed that PCDH10 inhibited the PI3K/Akt
      signaling pathway thus carrying out its suppressive function in HCC. This study
      provides insights into the tumorigenesis and progression of HCC, and puts forward
      the novel hypothesis that PCDH10 could be a new biomarker for HCC, or that
      combined with other molecular markers could increase the specificity and
      sensitivity of diagnostic tests for HCC. Restoration of PCDH10 could be a
      valuable therapeutic target for HCC.

PMID- 28498424
TI  - MicroRNA-15b promotes proliferation and invasion of non-small cell lung carcinoma
      cells by directly targeting TIMP2.
AB  - MicroRNA-15b (miR-15b) plays an important role in tumor development and
      progression. miR-15b functions differently in various types of malignant tumors.
      However, the expression pattern and role of miR-15b in non-small cell lung cancer
      (NSCLC) have not been elucidated. In the present study, we investigated the
      effect of miR-15b on the occurrence and development of lung cancer and the
      underlying mechanism. Lung cancer cell lines A549 and LTEP-a-2 were transfected
      with miR-15b inhibitor or mimic, respectively. Real-time PCR revealed that the
      expression level of miR-15b was significantly higher in human NSCLC tissues and
      NSCLC cells, than that of normal tissues and cells, respectively (P<0.05).
      Moreover, the effect of miR-15b on A549 and LTEP-a-2 cell viability, cell cycle,
      migration and invasion was further evaluated. Experiments indicated that miR-15b
      knockdown inhibited the viability, cell cycle, migration and invasion in A549
      cells, while upregulation of miR-15b exhibited the opposite effect. Tissue
      inhibitor of metallopeptidases 2 (TIMP2) protein and mRNA levels were
      downregulated after miR-15b overexpression in A549 and LTEP-a-2 cells,
      respectively. The dual-luciferase reporter gene assay implied that TIMP2 is a
      direct target gene of miR-15b. Our results indicate that high expression of miR
      15b is associated with NSCLC and suggest that miR-15b expression may be a novel
      biomarker for predicting clinical outcomes in NSCLC patients. The inhibition of
      miR-15b may even provide helpful therapeutic strategies for the treatment of
      NSCLC.

PMID- 28498425
TI  - Gene silencing of indoleamine 2,3-dioxygenase hinders tumor growth through
      angiogenesis inhibition.
AB  - The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in
      various types of tumors, but the relationship between IDO1 and tumor angiogenesis
      needs further delineation. We aimed to clarify the relationship between tumor
      angiogenesis and IDO1 expression, and to explore the possibility of IDO1
      targeting molecular therapy for lung cancer. For the first time, we found that
      silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro
      cancer cell invasion and migration. We further demonstrated that knockdown of
      IDO1 decreased the formation of vasculogenic mimicry. In addition to these in
      vitro findings, we also demonstrated that in vivo IDO1 gene silencing using short
      hairpin RNA (shRNA) delayed tumor onset and inhibited tumor growth in the mouse
      model. Immunostaining showed that IDO1 gene silencing inhibited tumor
      angiogenesis. Moreover, the expression of IDO1 was associated with microvessel
      density (MVD) labeled by CD34 and CD146. These findings indicate that IDO1 has
      the potential to participate in or contribute to the formation of new
      capillaries, supporting the applicability of IDO1-targeting molecular therapy in
      lung cancer.

PMID- 28498426
TI  - Identification of a missense HOXD13 mutation in a Chinese family with syndactyly
      type I-c using exome sequencing.
AB  - Syndactyly is one of the most common hereditary limb malformations, and is
      characterized by the fusion of specific fingers and/or toes. Syndactyly type I-c
      is associated with bilateral cutaneous or bony webbing of the third and fourth
      fingers and occasionally of the third to fifth fingers, with normal feet. The aim
      of the present study was to identify the genetic basis of syndactyly type I-c in
      four generations of a Chinese Han family by exome sequencing. Exome sequencing
      was conducted in the proband of the family, followed by direct sequencing of
      other family members of the same ancestry, as well as 100 ethnically-matched,
      unrelated normal controls. A missense mutation, c.917G>A (p.R306Q), was
      identified in the homeobox D13 gene (HOXD13). Sanger sequencing verified the
      presence of this mutation in all of the affected family members. By contrast,
      this mutation was absent in the unaffected family members and the 100 ethnically
      matched normal controls. The results suggest that the c.917G>A (p.R306Q) mutation
      in the HOXD13 gene, may be responsible for syndactyly type I-c in this family.
      Exome sequencing may therefore be a powerful tool for identifying mutations
      associated with syndactyly, which is a disorder with high genetic and clinical
      heterogeneity. The results provide novel insights into the etiology and diagnosis
      of syndactyly, and may influence genetic counseling and the clinical management
      of the disease.

PMID- 28498427
TI  - Effect of macrophages on breast cancer cell proliferation, and on expression of
      hormone receptors, uPAR and HER-2.
AB  - Malignant tumors, including breast cancers, are frequently infiltrated with
      innate immune cells and tumor-associated macrophages (TAMs) represent the major
      inflammatory component in stroma of many tumors. In this study, we examined the
      immunoreactivity of the macrophage markers CD68 and CD163 as well as the hormone
      receptors estrogen receptor alpha (ERalpha), progesterone receptor (PR), estrogen
      receptor beta1 (ERbeta1), human epidermal growth factor receptor 2 (HER-2),
      matrix metalloproteinase 9 (MMP-9), urokinase-type plasminogen activator receptor
      (uPAR) and the proliferations marker Ki67 in 17 breast cancer biopsies. The
      quantitative score for CD68+ and CD163+ strongly indicate M2 phenotype dominance
      in the currently investigated biopsies. We found that an increasing level of
      macrophages was negatively associated with ERalpha or PR, whereas a positive
      association was observed for Ki-67 or uPAR. No significant association could be
      seen between the level of macrophage and HER-2, ERbeta1 or MMP-9 expression.
      Effect of conditioned media (CM) generated from cultured human M1 and M2
      macrophage phenotypes were investigated on the proliferation and expression of
      selected markers in the T47D breast cancer cell line. We found that in contrast
      to the in vivo situation, in particularly the CM from M1 macrophages decreased
      the growth and Ki67 expression in T47D, and significantly increased ERbeta1 mRNA
      levels. Moreover, in accordance to the in vivo situation the CM from the
      macrophages decreased the expression of ERalpha protein as well as ERalpha or PR
      mRNA. In conclusion our results show that macrophages alone have the capability
      to decrease the tumor cell expression of ERalpha and PR in vitro. In the tumor
      environment in vivo macrophages also contribute to an increase in tumor cell
      expression of uPAR and Ki67, suggesting that macrophages are involved in
      impairing the prognosis for breast cancer patients.

PMID- 28498428
TI  - Differential expression profiles of microRNAs as potential biomarkers for the
      early diagnosis of lung cancer.
AB  - Lung cancer is one of the most lethal malignancies worldwide. To reduce the high
      morbidity and mortality of the disease, sensitive and specific biomarkers for
      early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be
      potential biomarkers for the early diagnosis and treatment of cancer. In this
      study, the microarray of miRNAs and mRNAs on the same samples was performed and
      the intersection taken with The Cancer Genome Atlas (TCGA) lung cancer
      miRNA/RNAseq dataset. Then, miRNA-mRNA regulatory network was constructed to
      identify miRNA candidates associated with lung cancer through integrating gene
      expression and miRNA-target prediction. Furthermore, the expression levels of
      miRNA candidates were validated by stem-loop real-time reverse transcription PCR
      (qRT-PCR) in larger lung cancer population. The relationship between signature
      miRNAs and the risk of lung cancer were assessed by conditional logistic
      regression analysis. Diagnostic value of these miRNAs was determined by areas
      under receiver operating characteristic curves (ROC). The Affymetrix microarray
      analysis identified a total of 116 miRNAs and 502 mRNAs that could distinguish
      lung tumor tissues from adjacent non-tumor tissues, of which 70 miRNAs and 136
      mRNAs were upregulated, while 46 miRNAs and 366 mRNAs were downregulated,
      respectively. In combination with TCGA analysis, we identified 32 miRNAs and 377
      mRNAs related to lung cancer. Then, 28 key miRNAs related to 61 inter-section
      mRNAs were identified by miRNA-mRNA network analysis. The miRNA function analysis
      was indicative of that 18 upregulated and 10 downregulated miRNAs involved in
      signaling pathways related to Environmental Information Processing and Human
      Diseases. Population result showed that the expression of 7 miRNAs (miR-205-5p,
      miR-3917, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p and miR-27a-5p) was
      consistent with the analysis result of microarray and TCGA. In addition,
      upregulation of miR-205-5p, miR-3917 and downregulation of miR-30a-3p, miR-30a
      5p, miR-30c-2-3p, miR-30d-5p, miR-27a-5p increased the risk of lung cancer by
      conditional logistic regression analysis. The diagnostic accuracy of miR-205-5p,
      miR-3917, miR-27a-5p, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p showed
      that their corresponding AUCs were 0.728, 0.661, 0.637, 0.758, 0.772, 0.734,
      0.776, respectively. Therefore, there are a set of signature miRNAs which may be
      promising biomarkers for the early screening of high-risk populations and early
      diagnosis of lung cancer.

PMID- 28498429
TI  - SBI0206965, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell
      growth by modulating both autophagy and apoptosis pathways.
AB  - Lung cancer is a major public health problem worldwide. Non-small cell lung
      cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently
      sparked great interest, and it is thought to participate in a variety of
      diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a
      serine/threonine kinase, plays a central role in the autophagy pathway. However,
      the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines
      exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with
      prognosis in lung cancer patients. Knockdown of Ulk1 or the inhibition of Ulk1 by
      the selective inhibitor SBI0206965, inhibited cell proliferation, induced cell
      apoptosis and enhanced the sensitivity of cisplatin against NSCLC cells.
      Moreover, we demonstrated that Ulk1 exerted oncogenic activity in NSCLC by
      modulating both autophagy and apoptosis pathways. Inhibition of autophagy by
      SBI0206965 sensitized NSCLC cells to cisplatin by inhibiting cisplatin induced
      cell-protective autophagy to promote apoptosis. Furthermore, SBI0206965 promoted
      apoptosis in NSCLC cells independent of autophagy, which was partly mediated by
      destabilization of Bcl2/Bclxl. In summary, our results show that inhibition of
      Ulk1 suppresses NSCLC cell growth and sensitizes NSCLC cells to cisplatin by
      modulating both autophagy and apoptosis pathways, and that Ulk1 might be a
      promising target for NSCLC treatment.

PMID- 28498430
TI  - UVA-induced upregulation of progerin suppresses 53BP1-mediated NHEJ DSB repair in
      human keratinocytes via progerin-lamin A complex formation.
AB  - Ultraviolet (UV) radiation is the primary risk factor underlying photoaging and
      photocarcinogenesis. Mounting research has focused on the role of DNA damage
      response pathways in UV-induced double-strand break (DSB) repair. In the present
      study, we hypothesized that UVA-induced aberrant progerin upregulation may
      adversely affect p53-binding protein 1 (53BP1)-mediated non-homologous end
      joining (NHE) DSB repair in human keratinocytes. Basal cell carcinoma (BCC)
      tumors and matching normal skin tissue were sampled (n=200) to investigate
      whether human keratinocytes display dysregulated progerin expression as a
      function of advancing age and BCC status. Newborn foreskin samples (n=9) were
      used as a source for primary keratinocyte cultures. We investigated the effects
      of UVA radiation on progerin and lamin A expression as well as the effects of the
      silencing of progerin on lamin A protein expression in UVA-irradiated
      keratinocytes. We investigated whether blocking progerin-lamin A interaction was
      able to rescue UVA-induced lamin A protein downregulation, 53BP1 downregulation
      and 53BP1-mediated NHEJ DSB repair activity. Progerin upregulation in adult
      keratinocytes was associated with advancing age, not BCC status. In vitro, UVA
      exposure significantly upregulated progerin expression by favoring alternative
      LMNA gene transcript splicing. UVA exposure significantly downregulated free
      (unbound) lamin A protein levels via progerin-lamin A complex formation. UVA
      exposure significantly decreased 53BP1 protein levels via enhanced progerin-lamin
      A complex formation. UVA-induced progerin-lamin A complex formation was largely
      responsible for suppressing 53BP1-mediated NHEJ DSB repair activity. The present
      study is the first to demonstrate that UVA-induced progerin upregulation
      adversely affects 53BP1-mediated NHEJ DSB repair in human keratinocytes via
      progerin-lamin A complex formation.

PMID- 28498431
TI  - PRKDC regulates chemosensitivity and is a potential prognostic and predictive
      marker of response to adjuvant chemotherapy in breast cancer patients.
AB  - DNA-dependent kinase catalytic subunit (DNA-PKcs) is a critical component of DNA
      repair machinery and is found to be up- or down-regulated in different cancer
      types. However, its clinical significance in breast cancer remains unclear. To
      this end, quantitative PCR was performed to measure PRKDC expression level in 59
      pairs of breast cancer tissues and the non-tumor adjacent tissues (NATs). The
      correlation between PRKDC expression and overall survival (OS) as well as the
      prognostic value of PRKDC were analyzed. In vitro and in vivo effects of PRKDC on
      chemosensitivity were evaluated in MCF-7 cells. We found that PRKDC expression
      was significantly increased in breast cancer tissue samples compared with NATs.
      High PRKDC expression was associated with higher tumor grade (P=0.001), positive
      lymph node metastasis (P=0.0357) and chemoresistance (P=0.0006). Furthermore,
      PRKDC expression was significantly correlated with OS in breast cancer patients
      with (0.0101) or without (P=0.0216) receiving chemotherapy. PRKDC was an
      independent prognostic factor of OS in breast cancer (P=0.022, hazard ratio=2.69,
      95% confidence interval: 1.81-3.84). Moreover, downregulation of PRKDC sensitized
      MCF-7 cells to chemo-drugs both in vitro and in a xenografted mouse model.
      Collectively, our study demonstrated that PRKDC is a prognostic biomarker for
      chemoresistance in breast cancer patients.

PMID- 28498432
TI  - Time- and oxygen-dependent expression and regulation of NDRG1 in human brain
      cancer cells.
AB  - N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the
      potential to suppress metastasis, invasion and migration of cancer cells. It is
      regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation
      is both induced and controlled by HIF-1alpha-dependent and -independent pathways
      under hypoxic conditions. However, there are profound differences in the way
      NDRG1 expression is regulated by HIF-1alpha and other transcription factors.
      Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and
      protein expression in human glioblastoma cell lines in extreme hypoxia and after
      re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the
      regulation of NDRG1 to the transcription factors HIF-1alpha, SP1, CEBPalpha, YB-1
      and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87
      MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O2)
      conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF
      1alpha SP1, CEBPalpha, YB-1 and Smad7 was measured using semi-quantitative RT-PCR
      analysis. Their protein expression was analyzed using western blotting. Our
      experiments revealed that long-term (24 h), but not short-term hypoxia led to the
      induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was
      found to correlate with the protein expression of HIF-1alpha, SP1, CEBPalpha, YB
      1 and Smad7. The present study suggests for the first time that SP1 regulates
      NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along
      with HIF-1alpha, CEBPalpha, YB-1 and Smad7. These molecules, each separately or
      in combination, may possess the potential to become target molecules for
      antitumor therapeutic approaches particularly in human brain tumors.

PMID- 28498433
TI  - Curcumin induces apoptotic cell death and protective autophagy in human gastric
      cancer cells.
AB  - Curcumin possesses an anticancer effect against a wide assortment of tumors with
      selective cytotoxicity for tumor cells. However, the mechanism involved in the
      curcumin-induced anticancer effect remain unclear. In the present study, we
      investigated the efficacy of curcumin against human gastric cancer cell growth
      and the molecular mechanism involved. Our results demonstrated that curcumin
      inhibited the viabilities of gastric cancer cell lines BGC-823, SGC-7901 and MKN
      28 in both a time- and dose-dependent manner. In addition, curcumin treatment
      induced gastric cancer cell apoptosis in a dose-responsive manner. Western
      blotting of apoptosis-related proteins further confirmed the pro-apoptotic
      potential of curcumin. After exposure to curcumin, a robust induction of
      autophagy was observed in gastric cancer cells, which was characterized by the
      formation of acidic vesicular organelles (AVOs), conversion of LC3-I to LC3-II
      and an increase in the levels of autophagy-related proteins. Activation of the
      PI3K/Akt/mTOR signaling pathway was suppressed in gastric cancer cells with
      curcumin treatment. However, administration of the autophagy inhibitor 3
      methyladenine (3-MA) significantly promoted the apoptotic cell death induced by
      curcumin. Collectively, our findings provide new evidence that curcumin induces
      apoptotic cell death and protective autophagy in human gastric cancer cells in
      vitro. Autophagy inhibitor treatment may provide a novel and effective strategy
      for improving the anticancer effect of curcumin against gastric cancer.

PMID- 28498434
TI  - A ligand-based and enediyne-energized bispecific fusion protein targeting
      epidermal growth factor receptor and insulin-like growth factor-1 receptor shows
      potent antitumor efficacy against esophageal cancer.
AB  - Recent studies have revealed that the epidermal growth factor receptor (EGFR) and
      insulin-like growth factor-1 receptor (IGF-1R) are overexpressed in various types
      of human tumors and are attractive targets for anticancer drugs. In the present
      study, the expression of EGFR and IGF-1R in esophageal squamous cell carcinoma
      (ESCC) and adjacent normal tissues in a tissue microarray was firstly detected by
      immunohistochemical staining. In addition, their co-overexpression was observed
      in 48 out of 75 (64%) patients. Based on the findings, the antitumor activity of
      an EGFR/IGF-1R bispecific and enediyne-energized fusion protein EGF-LDP-IGF-AE,
      which we constructed recently by fusing two ligands (EGF and IGF-1) with an
      enediyne antibiotic lidamycin (LDM), on ESCC were evaluated. Binding assay
      indicated that the EGF-LDP-IGF protein bound to esophageal cancer cells, and then
      internalized into the cytoplasm. In vitro, the enediyne-energized fusion protein
      EGF-LDP-IGF-AE exhibited extremely potent cytotoxicity to ESCC cells with IC50
      values between 10-10 and 10-15 mol/l. In vivo, EGF-LDP-IGF-AE also markedly
      suppressed the growth of human KYSE450 xenografts by 75.1% when administered at
      0.3 mg/kg in a nude mouse model, and its efficacy was significantly higher than
      that of LDM (at maximum tolerated dosage) and mono-specific counterparts. In
      addition, EGF-LDP-IGF-AE arrested cell cycle progression and it concentration
      dependently induced cell apoptosis as well as inhibited the activation of
      EGFR/IGF-1R and two major downstream signaling pathways (PI3K/AKT and RAS/MAPK).
      These data imply the potential clinical application of EGF-LDP-IGF-AE for ESCC
      patients with EGFR and/or IGF-1R overexpression.

PMID- 28498435
TI  - Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi-1 cells
      through upregulation of TRAIL death receptor expression, activation of caspase-8
      and inhibition of cFLIP.
AB  - Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable
      prognosis compared with other non-acute promyelocytic leukemia AML patients, only
      ~50% patients with this relatively favorable subtype can survive for 5 years and
      refractory/relapse is common in clinical practice. So it is necessary to find
      novel agents to treat this type of AML. In this study, the effects and the
      mechanisms of plumbagin and recombinant soluble tumor necrosis factor-alpha
      related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi-1 cells were
      primarily investigated. Plumbagin and/or rsTRAIL could significantly inhibit the
      growth of Kasumi-1 cells and induce apoptosis in vitro and in vivo. Plumbagin
      enhanced TRAIL-induced apoptosis of Kasumi-1 cells in association with
      mitochondria damage, caspase activation, upregulation of death receptors (DRs)
      and decreased cFLIP expression. The effects of plumbagin on the expression of
      DR5, Bax and cFLIP could be partially abolished by the reactive oxygen species
      (ROS) scavenger NAC. Glutathione (GSH) depletion by plumbagin increased the
      production of ROS. In vivo, there was no obvious toxic pathologic change in the
      heart, liver and kidney tissues in any of the groups. Comparing with the control
      mice, a significantly increased number of apoptotic cells were observed in the
      combined treated mice by flow cytometry. Plumbagin also increased the expression
      of DR4 and DR5 in cells of xenograft tumors. Collectively, our results suggest
      that both plumbagin and rsTRAIL could be used as a single agent or synergistical
      agents to induce apoptosis of leukemic Kasumi-1 cells in vitro and in vivo.

PMID- 28498436
TI  - Exposure to a chronic high-fat diet promotes atrial structure and gap junction
      remodeling in rats.
AB  - Obesity has been demonstrated to be linked to atrial fibrillation (AF) with
      atrial enlargement and tissue fibrosis. Long-term high calorie intake is the main
      reason for the prevalence of obesity. To investigate the possible causes of AF,
      such as chronic high-fat diet (HFD), and to identify the underlying mechanisms,
      the present study analyzed a variety of structural and gap junctional
      electrophysiological alterations in the atria of female rats fed an HFD. After
      consistent HFD feeding of female rats for 12 weeks, hematoxylin and eosin (H&E)
      and Masson's staining, RT-qPCR, western blotting, immunofluorescence and TUNEL
      staining were performed. In our study, approximately 3/5 of the HFD-fed rats (HFD
      OB, n=13) displayed a significant increase in body weight, while the other 2/5
      did not (HFD-NOB, n=8). In addition, the atrial weight of the HFD-OB and HFD-NOB
      rats was markedly heavier, as compared to the rats fed a normal diet (CT, n=20).
      According to the plasma lipid levels, both HFD-OB and HFD-NOB rats exhibited
      dyslipidemia. Furthermore, H&E staining revealed broadened interstitial space and
      myocyte disarray in atria of the HFD-fed rats (i.e., HFD-OB and HFD-NOB rats).
      Expression levels of atrial fibrosis relevant factors, transforming growth factor
      beta1 and matrix metalloproteinase-2, were significantly upregulated in the HFD
      fed rat atria. In addition, we found a gap junction remodeling with distinct
      alterations in expression and distribution of connexin 40 (Cx40) and Cx43 in the
      HFD-fed rat atria. Moreover, a modest increase in apoptotic cell death in both
      the HFD-OB and HFD-NOB rat atria was detected. Taken together, our findings
      demonstrated that the impact of chronic HFD on atria displayed in the diet
      induced obese rats was observed in HFD-fed rats in the absence of obesity as
      well.

PMID- 28498437
TI  - Autocrine expression of the epidermal growth factor receptor ligand heparin
      binding EGF-like growth factor in cervical cancer.
AB  - In cervical cancer, the epidermal growth factor receptor (EGFR) is overexpressed
      in 70-90% of the cases and has been associated with poor prognosis. EGFR-based
      therapy is currently being explored in cervical cancer. We investigated which
      EGFR ligand is primarily expressed in cervical cancer and which cell type
      functions as the major source of this ligand. We hypothesized that macrophages
      are the main source of EGFR ligands and that a paracrine loop between tumor cells
      and macrophages is responsible for ligand expression. mRNA expression analysis
      was performed on 32 cervical cancer cases to determine the expression of the EGFR
      ligands amphiregulin, beta-cellulin, epidermal growth factor (EGF), epiregulin,
      heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor
      alpha (TGFalpha). Subsequently, protein expression was determined
      immunohistochemically on 36 additional cases. To assess whether macrophages are
      the major source of EGFR ligands, immunohistochemical double staining was
      performed on four representative tissue slides. Expression of the chemokines
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and C-C motif ligand 2
      (CCL2) was determined by mRNA in situ hybridization. Of the known EGFR ligands,
      HB-EGF had the highest mRNA expression and HB-EGF and EGFR protein expression
      were highly correlated. Tumor specimens with high EGFR expression showed higher
      numbers of macrophages, and higher expression of GM-CSF and CCL2, but only a
      small subset (9%) of macrophages was found to be HB-EGF-positive. Strikingly, 78%
      of cervical cancer specimens were found to express HB-EGF. Standardized
      assessment of staining intensity, using spectral imaging analysis, showed that HB
      EGF expression was higher in the tumor compartment than in the stromal
      compartment. These results suggest that HB-EGF is an important EGFR ligand in
      cervical cancer and that cervical cancer cells are the predominant source of HB
      EGF. Therefore, we propose an autocrine EGFR stimulation model in cervical
      carcinomas.

PMID- 28498438
TI  - Dexamethasone reduces side population fraction through downregulation of ABCG2
      transporter in MCF-7 breast cancer cells.
AB  - Side population (SP) cells represent a rare population among breast cancer cells.
      SP cells have been reported to act as cancer stem-like cells, and to participate
      in the development of multidrug resistance via modulating the expression of ATP
      binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid
      drug that has been used as an adjuvant treatment to enhance the efficacy of
      chemotherapeutic agents; however, its effects in breast cancer have yet to be
      thoroughly investigated. In the present study, the effects of dexamethasone were
      investigated using the human MCF-7 breast cancer cell line, and SPs were examined
      in detail. Cellular proliferation, SP fractions and ABCG2 expression were
      examined following treatment of MCF-7 cells with dexamethasone. Dexamethasone was
      revealed to cause a dose- and time-dependent decrease in cancer cell
      proliferation, and it also decreased the size of the SP fraction of MCF-7 cells
      and the expression of the ABCG2 transporter. The effects of dexamethasone on
      cellular proliferation, SP fraction and ABCG2 expression were abolished following
      the administration of the glucocorticoid antagonist RU486. These results
      suggested that dexamethasone may target breast cancer cell SPs and thus increase
      the sensitivity of tumor cells to chemotherapy. Therefore, it may be hypothesized
      that dexamethasone can be used as a chemosensitizer in the adjuvant treatment of
      patients with breast cancer.

PMID- 28498439
TI  - Knockdown of CREB1 inhibits tumor growth of human gastric cancer in vitro and in
      vivo.
AB  - cAMP responsive element binding protein 1 (CREB1) gene, has been reported to play
      crucial roles in tumor progression and development in various types of cancer.
      Little is known, however, about its role and underlying mechanism in gastric
      cancer (GC). Herein, we investigated the biological roles and molecular mechanism
      of CREB1 in GC. The expression level was determined in four GC cell lines by
      quantitative RT-PCR and western blotting. Recombinant expression vector carrying
      small interfering RNA (siRNA) targeting CREB1 was constructed and then
      transfected into human GC cell line (SGC-7901). Cell proliferation, colony
      formation, cycle distribution, migration and invasion in vitro were determined by
      MTT, colony forming, flow cytometry, would healing and Transwell invasion assays
      after CREB1 knockdown. Tumor growth in vivo was assessed by measurement of tumor
      volume and weight in a nude mouse model. We found that CREB1 was highly expressed
      in the human GC cell lines. We also showed that knockdown of CREB1 in SGC-7901
      cells significantly inhibited cell proliferation, colony formation, migration and
      invasion and induced cell arrest at G1/G0 phase in vitro, as well as suppressed
      tumor growth in vivo. In addition, CREB1 knockdown was able to significantly
      reduce expression of its downstream target genes cyclin D1, Bcl-2 and MMP-9 in
      vitro and in vivo. These findings suggest that CREB1 may be a potential
      therapeutic target for the treatment of gastric cancer.

PMID- 28498440
TI  - Gastrin induces multidrug resistance via the degradation of p27Kip1 in the
      gastric carcinoma cell line SGC7901.
AB  - Multidrug resistance (MDR) is one of the major reasons for the failure of
      chemotherapy-based gastric carcinoma (GC) treatments, hence, biologically based
      therapies are urgently needed. Gastrin (GAS), a key gastrointestinal (GI)
      hormone, was found to be involved in tumor formation, progression, and
      metastasis. In this study, quantitative real-time polymerase chain reaction (qRT
      PCR) and immunohistochemical staining analysis revealed a high level of
      expression of GAS in drug-insensitive GC tissues (P<0.01) and similar results
      were revealed in GC cell lines SGC7901 and its multidrug-resistant variants
      SGC7901/VCR and SGC7901/ADR. We constructed a eukaryotic expression vector
      pCDNA3.1(+)/GAS for GAS overexpression and recombinant lentiviral vectors for
      specific siRNA (siGAS). Transfection of pCDNA3.1(+)/GAS increased (P<0.05) while
      transfection of siGAS (P<0.05) and co-treated with paclitaxel (TAX) and
      vincristine (VCR) combination (TAX-VCR) decreased (P<0.01) the cell viability of
      SGC7901, SGC7901/VCR and SGC7901/ADR. Apoptosis rates of SGC7901/VCR and
      SGC7901/ADR were reduced by pCDNA3.1(+)/GAS and increased by siGAS (P<0.05). The
      apoptosis rates of SGC7901/VCR, SGC7901/ADR and SGC7901 were all upregulated
      (P<0.01) when cells were co-treated with a combination of siGAS and TAX-VCR.
      Additionally, siGAS significantly downregulated the expression of Bcl-2 and
      multidrug-resistant associate protein (MRP1) and P-glycoprotein (Pgp) (P<0.05) in
      SGC7901/VCR and SGC7901/ADR cells. Moreover, GAS overexpression in SGC7901 cells
      significantly inhibited p27Kip1 expression but increased phosphorylation levels
      of p27Kip1 on Thr (187) and Ser (10) sites (P<0.05), as well as increasing
      nuclear accumulation of S-phase kinase-associated protein 2 (Skp2) and
      cytoplasmic accumulation of the Kip1 ubiquitination-promoting complex (KPC)
      (P<0.05). Silencing of Skp2 blocked the promoting effects of pCDNA3.1(+)/GAS on
      viability, the expression of MRP1 and Pgp and the inhibitory effects of
      pCDNA3.1(+)/GAS on apoptosis. In conclusion, we suggest that GAS contributes to
      the emergence of MDR of SGC7901 cells via the degradation of p27Kip1.

PMID- 28498441
TI  - Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor
      angiogenesis.
AB  - Angiogenesis is the main process responsible for tumor growth and
      metastatization. The principal effector of such mechanism is the vascular
      endothelial growth factor (VEGF) secreted by cancer cells and other components of
      tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to
      noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic
      drugs that block the VEGFR pathway. Aim of the present study was to radiolabel
      the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the
      expression of VEGFR in both cancer and endothelial cells in the tumor
      microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo
      to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with
      immunohistochemical analysis of excised tumors we found an inverse correlation
      between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive
      correlation with VEGF receptor expression (VEGFR1). Results of our studies
      indicate that endogenous VEGF production by cancer cells and other cells of tumor
      microenvironment should be taken in consideration when performing scintigraphy
      with radiolabeled VEGF, because of possible false negative results due to
      saturation of VEGFRs.

PMID- 28498442
TI  - Prognostic significance of altered miRNA expression in whole blood of OSCC
      patients.
AB  - Currently, there is a lack of blood markers for the detection of recurrent oral
      squamous cell carcinoma (OSCC). The present study aimed to investigate whether
      the aberrant expression of single microRNAs (miRNAs) in whole blood of patients
      could serve as a biomarker for persistent or recurrent OSCC. Whole blood of 2
      groups of formerly treated OSCC patients was investigated by RT-qPCR for their
      circulating miRNA profiles. The R-OC group included patients with recurrence of
      OSCC (n=21) and the NR-OC group included patients without recurrence (n=21). Fold
      changes and significance of the differences in miRNA expression levels between
      the groups were determined. A cut-off point (COP) for the discrimination between
      the R-OC and NR-OC groups was calculated and the significance between over/under
      expression of the miRNAs and the recurrence of malignancy was determined.
      Significant differences in the miRNA expression in whole blood of the R-OC and NR
      OC groups were found. The levels of miR-3651 and miR-494 were significantly
      increased and the level of miR-186 was significantly decreased in whole blood of
      the R-OC patients (pmiR-3651=0.001, pmiR-494=0.003 and pmiR-186=0.001). By the
      determination of the COP, increased or decreased expression of the markers was
      significantly correlated to the recurrence of the disease. Altered expression of
      miR-494, miR-3651 and miR-186 appears to be associated with the recurrence of
      OSCC. The present study may form the basis for establishing a blood test as a
      minimally invasive method for the detection of the recurrence of OSCC.

PMID- 28498443
TI  - Silencing of both ATF4 and PERK inhibits cell cycle progression and promotes the
      apoptosis of differentiating chondrocytes.
AB  - In the current study, we demonstrate that the silencing of protein kinase R (PKR)
      like endoplasmic reticulum (ER) kinase (PERK) and activating transcription factor
      6 (ATF4) (using small interfering RNA expression constructs) inhibits the
      chondrocyte cell cycle and proliferation in vitro and ex vivo. The silencing of
      PERK alone using siRNA against PERK (siPERK) led to arrest in the G1 phase, it
      decreased the number of cells in the S phase, and delayed progressoin to the G2-M
      phase. Co-transfection with siRNA against ATF (siATF4) led to a more profound
      inhibitory effect on cell cycle progression. Moreover, transfection with siPERK
      was associated with enhanced endoplasmic reticulum (ER) stress-induced apoptosis
      during bone morphogenetic protein 2 (BMP2)-induced chondrogenesis, and
      transfection with siATF4 exacerbated ER stress-related cell death. Data from flow
      cytometry (FCM), immunohistochemistry and TUNEL assays supported these findings
      in vitro and ex vivo. As shown by our results, the combined effect of the
      silencing of ATF4 and PERK led to the activation of an ER stress-specific caspase
      cascade in the cartilage tissue. On the whole, these findings reveal a new
      crucial combined effect of the silencing of PERK and ATF4 in modulating ER stress
      mediated apoptosis during chondrocyte differentiation and proliferation.

PMID- 28498444
TI  - High expression of PFTK1 in cancer cells predicts poor prognosis in colorectal
      cancer.
AB  - The serine/threonine-protein kinase PFTAIRE 1 (PFTK1) is a member of the cyclin
      dependent kinase family that is highly expressed in several malignant tumors,
      including hepatocellular carcinoma, esophageal, breast and gastric cancers, and
      glioma. It contributes to tumor progression and influences tumor prognosis.
      However, the expression and clinicopathological significance of PFTK1 in human
      colorectal cancer (CRC) remain to be elucidated. The present study aimed to
      examine the expression of PFTK1 and to evaluate the clinical significance of its
      expression in human CRC. Reverse transcription-quantitative polymerase chain
      reaction was performed on 10 fresh CRC and 10 surrounding normal tissue samples
      to detect and compare the expression of PFTK1 mRNA in CRC and normal colorectal
      tissues. Immunohistochemistry was performed on 179 CRC tissue specimens and 47
      control samples of normal colorectal lesions to characterize the expression of
      PFTK1 protein. Kaplan-Meier overall survival (OS) rate and Cox regression
      analyses were performed to evaluate the prognosis of patients with CRC. The
      expression of PFTK1 mRNA in CRC tissues (1.433+/-0.168) was significantly higher
      compared with normal tissues (0.853+/-0.107; t=1.97 ('t' was the value obtained
      from quantification of the mRNA data, following a paired t-test), P=0.008). High
      PFTK1 expression in cancerous cells was detected in 92 of the CRC specimens
      (51.40%), and high levels of PFTK1 were associated with tumor node metastasis
      (TNM) stage (P=0.042), tumor classification (P=0.022) and preoperative
      carcinoembryonic antigen (CEA) level (P<0.001). Kaplan-Meier OS rate and Cox
      regression analysis revealed that high PFTK1 expression level (hazard ratio
      (HR)=1.999; P=0.019) was an independent prognostic factor of CRC patients. The
      degree of differentiation (HR, 0.368, P=0.003), TNM classification (HR, 2.118,
      P=0.001) and preoperative CEA level (HR, 2.302, P=0.003) were also predictors of
      the prognosis of patients with CRC. The present study suggested that PFTK1 may be
      a potential anticancer target and prognostic marker in patients with CRC.

PMID- 28498445
TI  - Evaluation of expression of cancer stem cell markers and fusion gene in synovial
      sarcoma: Insights into histogenesis and pathogenesis.
AB  - Synovial sarcoma (SS) is an aggressive soft tissue tumor, with uncertain
      histological and cellular origin. SYT-SSX is considered to be responsible for
      sarcoma initiation and progression. The histogenesis and pathogenesis of this
      tumor are poorly understood, and prognosis of patients of SS is unsatisfactory.
      Recent studies have shown an association of cancer stem cells with the initiation
      and development of tumors. We explored immunohistochemical expression level of
      stem cell associated markers to determine the possible histogenesis and
      pathogenesis of SS. Fusion gene SYT-SSX was tested to assess diagnostic value and
      the molecular pathological features. We obtained the clinicopathological data of
      20 SS patients, immunohistochemical staining were used to evaluate stem cell
      associated markers included CD133, CD29, CD44, nestin, and ALDH1. Fusion gene SYT
      SSX was tested by reverse transcriptase-polymerase chain reaction (RT-PCR).
      Twenty SS cases were observed and the positive immuno-expression results showed
      CD133 (17/20), CD29 (11/20), CD44 (11/20), nestin (6/20), and ALDH1 (5/20).
      Fusion gene SYT-SSX was successfully detected by RT-PCR from 18 available
      samples. The expression of stem cell-associated markers (CD133, CD29, CD44,
      Nestin, and ALDH1) and clinical data (age, gender, sites, tumor size,
      histological type, tumor stage, and distant metastases) did not show
      statistically significant relationship (P>0.05), whereas, statistically
      significance between ALDH1 and metastases was observed (P<0.01). The ALDH1
      positive synovial sarcoma (ALDH1+ SS) cases had significantly poor prognosis
      compared to ALDH1 negative synovial sarcoma (ALDH1- SS) cases (P<0.05).
      Immunohistochemical results indicated different expression levels of the five
      cancer stem cell markers in SS suggesting that SS may arise from cancer stem
      cells. Fusion gene SYT-SSX may play a critical role in the molecular pathological
      of SS.

PMID- 28498446
TI  - Synergistic protective effect of FTY720 and vitamin E against simulated cerebral
      ischemia in vitro.
AB  - The purpose of the present study was to explore the combination effect of FTY720
      and vitamin E on cerebral ischemia. Astrocytes were isolated from newborn Sprague
      Dawley rats and were subjected to FTY720, vitamin E, or combination of the two.
      The astrocyte cultures were then exposed to oxygen-glucose deprivation (OGD) to
      simulate an ischemic model in vitro. Cell viability, lactate dehydrogenase (LDH)
      leakage and cell apoptosis were detected following 12 h of exposure to OGD. In
      addition, the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL
      1beta, total antioxidant capacity, intercellular adhesion molecule (ICAM)-1,
      vascular cell adhesion molecule (VCAM)-1, chemokine (C-X-C motif) ligand (CXCL)
      10, heme oxygenase (HO)-1 and superoxide dismutase (SOD)-1 were measured. Pre
      treatment with FTY720 or vitamin E significantly elevated the cell viability and
      decreased LDH release and number of apoptotic cells. Combination treatment with
      FTY720 and vitamin E demonstrated a synergistic protective effect on OGD-induced
      cell viability, toxicity and apoptosis. Pre-treatment with FTY720 markedly
      reduced the release of IL-1beta, TNF-alpha, IL-6, ICAM-1, VCAM-1 and CXCL-10, and
      pre-treatment with vitamin E increased the levels of antioxidant, HO-1 and SOD-1.
      However, pre-treatment with FTY720 combined with vitamin E revealed a synergistic
      effect. Pre-treatment with FTY720 combined with vitamin E exerts synergistic
      neuroprotective effects in the simulated cerebral ischemia in vitro.

PMID- 28498447
TI  - DEC2 expression antagonizes cisplatin-induced apoptosis in human esophageal
      squamous cell carcinoma.
AB  - Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated
      embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of
      Split subfamily of basic helix-loop-helix factors. Previous studies have
      demonstrated that DEC proteins are involved in the regulation of circadian
      rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and
      DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study,
      alterations in expression of apoptosis-related markers in human esophageal
      squamous cell carcinoma TE-11 cells treated with cisplatin were examined by
      western blot, while overall cell viability and apoptosis were analyzed by MTS
      assay and hematoxylin and eosin staining, respectively. Following cisplatin
      treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was
      upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited
      expression of the pro-apoptotic factor Bim and slightly increased the anti
      apoptotic factor Bcl-xL. However, overexpression of DEC1 during cisplatin
      treatment failed to affect expression of these markers. Additionally,
      overexpression of DEC2 improved cell viability and decreased cell apoptosis
      induced by cisplatin. These results suggested that DEC2 exhibits anti-apoptotic
      effects in TE-11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may
      therefore have therapeutic potential for the treatment of esophageal cancer, in
      combination with cisplatin.

PMID- 28498448
TI  - Sanguinarine protects against ovariectomy-induced osteoporosis in mice.
AB  - Natural compounds are alternative agents that have therapeutic potential for
      preventing and treating osteoporosis. Traditionally, sanguinarine has been used
      clinically due to its diverse biological properties, including antimicrobial,
      anti-inflammatory and anticancer effects. Recently, for the first time, it was
      reported that sanguinarine inhibits osteoclast differentiation and bone
      resorption by suppressing the tumor necrosis factor ligand superfamily member 11
      induced nuclear factor-kappaB and extracellular signal-regulated kinase signaling
      pathways in vitro. Therefore, the present study further investigated the
      pharmacological effect of sanguinarine on osteoporosis in vivo. Micro-computed
      tomography and histomorphometry analysis demonstrated that sanguinarine, at low
      and high concentrations, prevents ovariectomy (OVX)-induced bone loss. In
      addition, further investigation of the cellular response in vivo revealed that
      sanguinarine inhibited osteoclastic bone resorption and promoted osteoblastic
      bone formation in a dose-dependent manner. Therefore, the present study
      demonstrated that sanguinarine protected mice from OVX-induced osteoporosis by
      modulating bone remodeling, indicating that sanguinarine may have potential in
      the treatment of osteoporosis.

PMID- 28498450
TI  - [Corrigendum] miR-28-5p promotes the development and progression of ovarian
      cancer through inhibition of N4BP1.
AB  - Following the publication of this article, the authors noted that there was an
      error in the affiliations. Specifically, the affiliation of the first author JUAN
      XU should be: Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang
      University, Jinhua, Zhejiang 321000, P.R. China. [the original article was
      published in the International Journal of Oncology 50: 1383-1391, 2017; DOI:
      10.3892/ijo.2017.3915].

PMID- 28498449
TI  - Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine
      on acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the
      blood and may result from a variety of genetic disorders. The present study aimed
      to identify the underlying mechanisms associated with the therapeutic effects of
      decitabine and cytarabine on AML, using microarray analysis. The microarray
      datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus
      database. Differentially expressed genes (DEGs) and differentially methylated
      sites were identified in AML cells treated with decitabine compared with those
      treated with cytarabine via the Linear Models for Microarray Data package,
      following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed
      using the Database for Annotation, Visualization and Integrated Analysis
      Discovery. Genes corresponding to the differentially methylated sites were
      obtained using the annotation package of the methylation microarray platform. The
      overlapping genes were identified, which exhibited the opposite variation trend
      between gene expression and DNA methylation. Important transcription factor (TF)
      gene pairs were screened out, and a regulated network subsequently constructed. A
      total of 190 DEGs and 540 differentially methylated sites were identified in AML
      cells treated with decitabine compared with those treated with cytarabine. A
      total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA
      complexes and the nucleosome assembly. The 540 differentially methylated sites
      were located on 240 genes, including the acid-repeat containing protein (ACRC)
      gene that was additionally differentially expressed. In addition, 60 TF pairs and
      overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The
      regulated network included 68 nodes and 140 TF-gene pairs. The present study
      identified various genes including ACRC and proliferating cell nuclear antigen,
      in addition to various TFs, including TATA-box binding protein associated factor
      1 and CCCTC-binding factor, which may be potential therapeutic targets of AML.

PMID- 28498451
TI  - Differential effects of p38 and Erk1/2 on the chondrogenic and osteogenic
      differentiation of dental pulp stem cells.
AB  - The extracellular signal-regulated protein kinase 1/2 (Erk1/2) and p38 mitogen
      activated protein-kinase pathways serve important roles in the regulation of
      osteogenic and chondrogenic differentiation in mesenchymal stem cells (MSCs).
      However, the exact mechanism remains unclear, and the effect is controversial. In
      the present study, the effects of Erk1/2 and p38 on the osteogenic and
      chondrogenic differentiation of dental pulp stem cells (DPSCs) were compared in
      vitro. The results indicated that inhibition of Erk1/2 is able to enhance the
      osteogenic differentiation of DPSCs and inhibit chondrogenic differentiation,
      whereas inhibition of p38 demonstrated the opposite effect. When compared with
      previous studies, the present study further confirmed that Erk1/2 and p38 serve
      important, but complicated, roles in regulating the differentiation of MSCs.
      Different chemical and physical stimuli, cell types, culture methods, times of
      inhibitor administration and the dosage of the inhibitor may influence the effect
      of Erk1/2 and p38 on the differentiation of MSCs. The present study aims to
      better understand the mechanisms that control the differentiation of MSCs and may
      be helpful in creating more effective tissue regeneration.

PMID- 28498452
TI  - Calpain and AR-V7: Two potential therapeutic targets to overcome acquired
      docetaxel resistance in castration-resistant prostate cancer cells.
AB  - Docetaxel-based chemotherapy has been widely used as the first-line treatment for
      castration-resistant prostate cancer (CRPC) patients. However, the mechanisms of
      docetaxel-resistance remain unclear. In the present study with the establishment
      of 2 in vitro models of docetaxel-resistant CRPC cell sublines, we firstly
      reported that activation of calpain may play a promotional role in the resistance
      of docetaxel in prostate cancer, meanwhile using the calpain inhibitor combined
      with docetaxel improved the efficiency of docetaxel in docetaxel-resistant cell
      sublines. Moreover, we also found that the expression of androgen-independent
      constitutively and transcriptionally active androgen receptor splice variant-7
      (AR-V7) remained high in the docetaxel-resistant CRPC cell subline Rv1-DR, and
      that it may be involved in acquired docetaxel-resistance of CRPC. However, a
      novel importin-beta inhibitor (importazole) was only capable of slightly
      decreasing the transcriptional activity of the AR signaling pathway via blocking
      nuclear import of AR-FL and various non-specific AR-Vs, instead of AR-V7. These
      findings suggest that calpain and AR-V7 may serve as important biomarkers in the
      treatment of CRPC, and targeting calpain and AR-V7 may provide a new approach in
      overcoming docetaxel-resistance.

PMID- 28498453
TI  - The inhibition of microRNA-15a suppresses hepatitis B virus-associated liver
      cancer cell growth through the Smad/TGF-beta pathway.
AB  - In the present study, the role of microRNA-15a (miR-15a) was investigated in
      hepatitis B virus (HBV)-associated liver cancer. The results revealed that the
      expression levels of miR-15a were increased in HBV-associated liver cancer
      tissues compared with the levels in normal tumor-adjacent tissues. Moreover, Smad
      7 protein expression in patients with HBV-associated liver cancer was higher than
      that in normal tumor-adjacent tissues. In addition, miR-15a expression and Smad-7
      protein expression were increased in HepG2 hepatocellular carcinoma cells
      compared with that noted in L-02 normal hepatocytes. In HepG2 cells, miR-15a
      inhibition suppressed cell proliferation and increased Smad-7 protein expression.
      The inhibition of miR-15a was also demonstrated to decrease transforming growth
      factor (TGF)-beta1 protein expression and Smad-2, p-Smad-2 and Smad-4 expression
      levels in HepG2 cells. Furthermore, FSP1 protein expression and caspase-3/-7
      activities were enhanced by miR-15a inhibition in HepG2 cells compared with the
      control group. Treatment with recombinant TGF-beta1 was demonstrated to activate
      Smad-2/-4 and FSP1 protein expression and increase caspase-3/-7 activity in HepG2
      cells. Collectively, these findings demonstrate that the miR-15a/Smad-7/TGF-beta
      pathway is important in HBV-associated liver cancer.

PMID- 28498454
TI  - Identification of SETD2-NF1 fusion gene in a pediatric spindle cell tumor with
      the chromosomal translocation t(3;17)(p21;q12).
AB  - Spindle cell tumors are clinically heterogeneous but morphologically similar
      neoplasms. The term refers to the tumor cells' long and slender microscopic
      appearance. Distinct subgroups of spindle cell tumors are characterized by
      chromosomal translocations and also fusion genes. Other spindle cell tumors exist
      that have not yet been found to have characteristic, let alone pathognomonic,
      genetic or pathogenetic features. Continuous examination of spindle cell tumors
      is likely to reveal other subgroups that may, in the future, be seen to
      correspond to meaningful clinical differences and may even be therapeutically
      decisive. We analyzed genetically a pediatric spindle cell tumor. Karyotyping
      showed the tumor cells to carry a t(3;17)(p21;q12) chromosomal translocation
      whereas RNA sequencing identified a SETD2-NF1 fusion gene caused by the
      translocation. RT-PCR together with Sanger sequencing verified the presence of
      the above-mentioned fusion transcript. Interphase FISH analysis confirmed the
      existence of the chimeric gene and showed that there was no reciprocal fusion.
      The fusion transcript codes for a protein in which the last 114 amino acids of
      SETD2, i.e., the entire Set2 Rpb1 interacting (SRI) domain of SETD2, are replaced
      by 30 amino acids encoded by the NF1 sequence. The result would be similar to
      that seen with truncating SETD2 mutations in leukemias. Absence of the SRI domain
      would result in inability to recruit SETD2 to its target gene locus through
      binding to the phosphor-C-terminal repeat domain of elongating RNA polymerase II
      and may affect H3K36 methylation. Alternatively, loss of one of two functional
      SETD2 alleles might be the crucial tumorigenic factor.

PMID- 28498455
TI  - Overexpression of MAGEA2 has a prognostic significance and is a potential
      therapeutic target for patients with lung cancer.
AB  - Melanoma-associated antigens (MAGE) are expressed in different type of cancers
      including lung cancer and have been shown to be functionally related to p53 tumor
      suppressor gene. Little is known about the relationship between MAGE genes and
      p53 aberrant expression in lung cancer. The aims of this study were to observe
      the expression of MAGEA2, examine the role of MAGEA2 in lung cancer survival,
      investigate its correlation between MAGEA2 and p53, and explore its
      clinicopathologic significance as a prognostic marker. Quantitative reverse
      transcription-polymerase chain reaction was performed to detect the expression of
      MAGEA2 using 36 primary tumors and 31 metastatic lymph nodes from patients with
      lung cancer. The role of MAGEA2 in cancer cell growth and in the regulation of
      p53 downstream genes were examined using small interfering RNA. The expression of
      MAGEA2 and p53 were analyzed immunohistochemically using tissue microarray from
      353 resected lung specimens. High-level expression of MAGEA2 (High-MAGEA2) was
      confirmed in lung tumors with high frequency. Inhibiting MAGEA2 expression
      effectively suppressed cancer cell growth and decreased the expression of p53
      downstream target genes in vitro. In adenocarcinoma, High-MAGEA2 was strongly
      associated with aberrant p53 expression (P<0.001) and was associated with worse
      clinical outcomes (5-year OS, 87.1% in low vs. 74.1% in high, P=0.014). Aberrant
      p53 expression was also significant worse prognostic factor (P=0.029). Among the
      adenocarcinoma patients with wild-type p53, High-MAGEA2 had poorer prognosis than
      low-level MAGEA2 groups (5-year OS, 90.1% vs. 72.1%, P=0.037), whereas had no
      difference in p53 aberrant tumors. On multivariate analysis, MAGEA2 was
      independently associated with survival (hazard ratio; 2.12, P=0.030). In
      conclusion, suppression of MAGEA2 in lung cancer cells significantly reduced the
      growth/survival of cancer cells. High-MAGEA2 was identified as an independent
      prognostic factor in lung adenocarcinoma. Specific inhibition of MAGEA2 may be a
      promising therapeutic strategy for patients with lung cancer.

PMID- 28498456
TI  - miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal
      cancer.
AB  - Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the
      pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported
      to play either oncogenic or tumor suppressive roles in human cancers. A recent
      study reported that the levels of miR-944 in recurrent CRC patients were
      evidently lower than that in non-recurrent cases, suggesting that miR-944 may
      function as a tumor suppressive miRNA in CRC. Yet, the clinical value and
      biological function of miR-944 remain rarely known in CRC. In the present study,
      we present that miR-944 level in CRC tissues is notably reduced compared to
      matched non-cancerous specimens. Its decreased level is evidently correlated with
      malignant clinical parameters and poor prognosis of CRC patients. Accordingly,
      the levels of miR-944 were obviously downregulated in CRC cells. Ectopic
      expression of miR-944 in CRC cells prominently inhibits the migration and
      invasion of tumor cells, while miR-944 knockdown increased these effects of CRC
      cells. Mechanically, miR-944 negatively regulated the metastasis-associated in
      colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a
      downstream molecule of miR-944 in CRC. An inversely correlation between miR-944
      and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1
      expression could abrogate the anti-metastatic effects of miR-944 on CRC cells
      with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be
      implicated with the function of miR-944 in CRC cells. Altogether, miR-944
      potentially act as a prognostic predictor and a drug-target for CRC patients.

PMID- 28498457
TI  - SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related
      tumor markers and serum tumor markers in gastric adenocarcinoma patients.
AB  - The expression of P53 was previously found by us significantly correlated with
      maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC)
      patients. Hence, the aim of this study was to clarify the relationship between
      SUVmax and the status of the chemotherapy-related tumor marker expression or
      serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric
      adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were
      enrolled in this study. Immunohistochemistry was performed to detect changes of
      Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was
      used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients.
      Then, the relationships between these parameters above were assessed by Spearman
      correlation analysis. Also, receiver-operating characteristic (ROC) curve was
      performed to determine the best cut-off value of SUVmax for suggesting
      chemotherapy resistant tumor markers. Besides, we identified a linear correlation
      to estimate the equations between SUVmax and the serum tumor markers. Our results
      showed that higher SUVmax was detected in patients with positive expression of
      Her-2 and P53, compared with negative groups. The Spearman correlation analysis
      showed that SUVmax was associated with Her-2 or P53 with the moderate relevant
      Pearson correlation coefficient. ROC curve analysis showed that the sensitivity
      and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off
      value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship
      between SUVmax and serum tumor markers were analyzed by linear correlation
      analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to
      establish an equation for SUVmax by the linear regression models. These results
      suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her
      2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients.
      However, before PET/CT scanning, serum tumor markers could be used to calculate
      the SUVmax approximately.

PMID- 28498458
TI  - Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of
      colorectal cancer cells by activating miR-34a.
AB  - Scutellaria barbata D. Don (SB) is a well known formula in traditional Chinese
      medicine, which exhibits potent anticancer effects on various cancers. Many
      miRNAs play crucial roles in the regulation of cancer, for instance, miR-34a
      functions as a tumor suppressor, and is often downregulated during cancer. In
      this study, we investigated the role of ECSB in suppressing the growth of human
      colon cancer HCT-8 cells, and whether this is mediated by regulation of miR-34a
      and its downstream target genes, using real-time PCR and western blot analysis.
      ECSB treatment significantly inhibited the proliferation of HCT-8 cells and
      promoted apoptosis in a dose-dependent manner. In addition, ECSB treatment
      significantly increased the level of miR-34a expression and decreased the levels
      of Bcl-2, Notch1/2 and Jagged1 expression. Furthermore, knockdown of miR-34a
      expression through transfection of anti-miR-34a oligonucleotide was significantly
      reversed by ECSB treatment. Likewise, knockdown of miR-34a resulted in
      significant upregulation of Bcl-2, Notch1/2 and Jagged1 expression, which was
      reversed following ECSB treatment. Therefore, this study reveals that ECSB
      inhibited cancer cell growth via promoting apoptosis and inhibiting
      proliferation, through regulation of miR-34a. These findings further support the
      use of ECSB as an effective therapeutic agent against colon cancer.

PMID- 28498459
TI  - Inhibitors of PARP-1 exert inhibitory effects on the biological characteristics
      of hepatocellular carcinoma cells in vitro.
AB  - It has been confirmed that the inhibitors of poly ADP-ribose polymerF(^9ase-1
      (PARP-1) can inhibit the proliferation, apoptosis and invasion of tumor cells.
      However, the effects of inhibitors of PARP-1 on hepatocellular carcinoma remain
      to be elucidated. The aim of the present study was to investigate the effect of
      three types of PARP-1 inhibitor on the proliferation, apoptosis and migration of
      hepatocellular carcinoma in vitro. An MTT assay was performed to detect the
      proliferation of HepG2 cells following treatment with the PARP-1 inhibitors,
      AG014699, BSI-201 and AZD-2281. Flow cytometry was used to detect the apoptosis
      of HepG2 cells, Western blot analysis was used to detect the protein expression
      of Casepase-3, Casepase-8, B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax),
      Bcl-2, phosphatase and tensin homolog (PTEN), tissue inhibitor of
      metalloproteinase (TIMP) 3 and matrix metalloprotease (MMP) 3. A Transwell assay
      was performed to detect the migration of HepG2 cells. The results showed that
      AG014699, BSI-201 and AZD-2281 had an inhibitory effect on the proliferation of
      HepG2 cells in a time- and concentration-dependent manner. AG014699 at
      concentrations of 10, 30 and 50 umol/l, and BSI-201 at concentrations of 20, 40
      and 60 umol/l induced the apoptosis of HepG2 cells, and the apoptotic rates were
      particularly high at 48 h (31, vs. 0.01%; P<0.01 and 24.12, vs. 0.03%,
      respectively; P<0.01). The protein expression levels of Caspase 3, Caspase 8,
      Bax, PTEN and TIMP 3 increased with increasing drug concentrations, whereas the
      protein levels of Bcl-2 and MMP3 decreased with increasing drug concentrations,
      and were significantly different compared with those in the control group
      (P<0.01). In conclusion, AG014699, BSI-201 and AZD-2281 inhibitors of PARP-1
      significantly inhibited the proliferation of HepG2 cells, however, AG014699 and
      BSI-201 demonstrated more sensitivity, induced apoptosis and inhibited migration
      of the hepatocellular carcinoma cells, which may be associated with alterations
      of the apoptosis signaling pathway and the expression of proteins associated with
      migration.

PMID- 28498460
TI  - MCM7 amplification and overexpression promote cell proliferation, colony
      formation and migration in esophageal squamous cell carcinoma by activating the
      AKT1/mTOR signaling pathway.
AB  - The roles and mechanisms of mini-chromosome maintenance complex component 7
      (MCM7) amplification and overexpression in esophageal carcinogenesis were
      investigated. By analyzing the TCGA datasets, we found that MCM7 was amplified in
      approximately 12% of esophageal squamous cell carcinomas (ESCCs), and in more
      than 4% of head and neck squamous cell carcinomas and stomach carcinomas.
      Overexpression of MCM7 was further verified in three independent GEO datasets of
      esophageal cancer. Knockdown of MCM7 using two siRNAs significantly inhibited
      cell proliferation, colony formation and migration of KYSE510 and EC9706 cells in
      vitro. Noteworthy, we further found that silencing of MCM7 suppressed the
      phosphorylation of AKT1 and mTOR both in KYSE510 and EC9706 cells, and reduced
      the cell cycle regulatory proteins cyclin D1, cyclin E2 and CDK2. Taken together,
      our findings suggested that MCM7 promoted tumor cell proliferation, colony
      formation and migration of ESCC cells via activating AKT1/mTOR signaling pathway.

PMID- 28498461
TI  - Increased production of human fibroblast growth factor 17 in Escherichia coli and
      proliferative activity in NIH3T3 cells.
AB  - Fibroblast growth factor 17 (FGF17) is a novel member of the FGFs family, which
      is essential for cell development, tissue repair, tumor growth and invasion. The
      aim of the current study was to obtain a high expression level of recombinant
      human FGF17 (rhFGF17), including soluble proteins and inclusion bodies. An
      optimized rhFGF17 cDNA sequence was cloned into a pET3a vector, then the pET3a
      hFGF17 vector was transformed into BL21(DE3)pLysS Escherichia coli cells.
      Expression was induced by optimizing the conditions using isopropyl beta-D-1
      thiogalactopyranoside (IPTG) and it was confirmed that a 24-h exposure to 0.8 mM
      IPTG at 16C provided the optimal condition for soluble hFGF17. Furthermore, for
      the inclusion bodies, the optimal condition was a 4-h exposure to 0.4 mM IPTG at
      37C. Two forms of rhFGF17 protein were purified by heparin affinity and SP
      Sepharose Fast Flow chromatography. MTT assays demonstrated that the purified
      rhFGF17 exerted an important effect on the proliferative activity of NIH3T3
      cells, although there was no significant difference when compared with standard
      rhFGF17. Thus, an optimal and economic expression system was created in the
      present study for rhFGF17 in E. coli. This expression strategy enables the
      preparation of sufficient and highly bioactive rhFGF17 for further investigation
      of underlying mechanisms.

PMID- 28498462
TI  - Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma.
AB  - Reelin, a secreted glycoprotein, was recently demonstrated to be involved in the
      pathogenesis of cancer. However, its oncogenic activities in non-Hodgkin lymphoma
      (NHL) remain unclear. Therefore, we aimed to evaluate the functional role of
      reelin in NHL, and the underlying molecular mechanisms. In the present study, we
      analyzed reelin expression in lymphoma tissues and cell lines using
      immunohistochemistry, immunofluorescence staining, qRT-PCR and western blotting.
      Then, the expression of Reelin was silenced with short hairpin RNA (shRNA)
      expressing plasmid in the NHL cell line A20. The effects of Reelin depletion on
      cell growth, migration and invasion in vitro were determined by CCK-8 and
      transwell assays. Flow cytometry was used to examine the cell cycle status and
      cellular apoptosis. Hoechst 33258 fluorescence staining was used to analyze
      morphologic changes caused by apoptosis. The second messenger, cAMP was analyzed
      by ELISA. In addition, we used nude mice to evaluate the tumorigenic ability of
      reelin. Aberrant upregulated levels of mRNA and protein of reelin were observed
      in lymphoma tissues and cell lines. Knockdown of reelin suppressed lymphoma
      growth, migration and invasion ability of A20. Furthermore, reelin depletion
      induced cell cycle arrest in G0/G1 phase and promoted apoptosis of A20 cells.
      Further analysis indicated that knockdown of reelin downregulated the expression
      of CDK5 and IL-10 and activated caspase-3 in shReelin group. ELISA assay showed
      cAMP at a lower level in shReelin group. SQ22536, a cAMP pathway inhibitor,
      treated A20 cells and revealed likely effects. The tumor size in a mouse model
      injected shReelin was significantly smaller than controls. There results suggest
      that reelin played essential roles in the development of lymphoma and might be a
      potential drug target in lymphoma.

PMID- 28498463
TI  - miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell
      lung cancer by targeting Sirt1.
AB  - The present study determined the role and mechanism of miR-138 in non-small cell
      lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were
      collected. The expression of miR-138 in tissues and cell lines were determined by
      real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3
      cells in vitro, and then the effects of miR-138 on lung cancer cell
      proliferation, cell cycle, invasion and metastasis were investigated by CCK-8
      assay, Transwell and flow cytometry, respectively. The protein expression of the
      potential target gene Sirt1 in lung cancer cells were determined by western blot
      analysis. Dual-luciferase reporter assay was performed to further confirm whether
      Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly
      lower in lung cancer tissues and was negatively correlated to the differentiation
      degree and lymph node metastasis of lung cancer. In vitro experiment results
      showed that miR-138 inhibited lung cancer cell proliferation, invasion and
      migration. It was verified that miR-138 could downregulate Sirt1 protein
      expression, inhibit epithelial-mesenchymal transition (EMT), decrease the
      activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual
      luciferase reporter assay demonstrated that miR-138 could directly regulate
      Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and
      biological function changes. Western blot analysis and confocal microscopy
      results indicated that overexpression of miR-138 or interference of Sirt1
      expression could inhibit lung cancer cell autophagy activity possibly through
      AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung
      cancer. It may inhibit the proliferation, invasion and migration of lung cancer
      through downregulation of Sirt1 expression and activation of cell autophagy. The
      downregulation of miR-138 is closely related to the development of lung cancer.

PMID- 28498464
TI  - Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2
      microglial cells.
AB  - S100A8/A9, a heterodimer of the two calcium-binding proteins S100A8 and S100A9,
      has emerged as an important proinflammatory mediator in acute and chronic
      inflammation. However, whether S100A8/A9 is implicated in microglial-induced
      neuroinflammatory response remains unclear. Here, we found that S100A8/A9
      significantly increased the secretion of proinflammatory cytokines inclu-ding
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cultured BV-2
      microglial cells. Inhibition of the Toll-like receptor 4 (TLR4) and the receptor
      for advanced glycation end-products (RAGE) with C225 and a RAGE-blocking
      antibody, respectively significantly reduced the secretion of TNF-alpha and IL-6
      from S100A8/A9-stimulated BV-2 microglial cells. Furthermore, S100A8/A9 markedly
      enhanced the nuclear translocation of NF-kappaB p65 and the DNA-binding
      activities of NF-kappaB in BV-2 microglial cells, and suppression of ERK and
      JNK/MAPK signaling pathways by PD98059 or SP600125 significantly inhibited NF
      kappaB activity and the release of TNF-alpha and IL-6 in the S100A8/A9-treated BV
      2 microglial cells. Our data also showed that inhibition of NF-kappaB with
      pyrrolidine dithiocarbamate (PDTC) significantly reduced the secretion of TNF
      alpha and IL-6 from BV-2 microglial cells treated with S100A8/A9. Taken together,
      our data suggest that S100A8/A9 acts directly on BV-2 microglial cells via
      binding to TLR4 and RAGE on the membrane and then stimulates the secretion of
      proinflammatory cytokines through ERK and JNK-mediated NF-kappaB activity in BV-2
      microglial cells. Targeting S100A8/A9 may provide a novel therapeutic strategy in
      microglial-induced neuroinflammatory diseases.

PMID- 28498465
TI  - Identification of a novel hypertrophic cardiomyopathy-associated mutation using
      targeted next-generation sequencing.
AB  - Hypertrophic cardiomyopathy (HCM), one of the most common forms of myocardial
      diseases, is the major cause of sudden cardiac death in young adults and
      competitive athletes. Analyses of gene mutations associated with HCM are valuable
      for its molecular diagnosis, genetic counseling, and management of familial HCM.
      To dissect the relationship between the clinical presentation and gene mutations
      of HCM, the genetic characterizations of 19 HCM-related genes in 18 patients (8
      cases from 6 pedigrees with familial HCM and 10 cases without familial HCM) were
      detected using next-generation sequencing (NGS). As a result, 12 disease-related
      mutations were identified in the 18 subjects, including 6 single mutations and 3
      double mutations [MYBPC3 (p.Gln998Glu) plus TNNI3 (p.Arg145Gly), PRKAG2
      (p.Gly100Ser) plus MYBPC3 (p.Lys1209Serfs*28) and TNNI3 (p.Glu124Gln) plus GLA
      (p.Trp47*)]. The 3 heterozygous double mutations were discovered for the first
      time in the malignant familial HCM patients. Of the 6 single mutations, a novel
      mutation was found in tafazzin (TAZ, p.Ile208Val), and a mutation in beta-myosin
      heavy chain gene (MYH7, p.Arg54Gln), which was reported as rare in the general
      population, was firstly found in one HCM patient. Identification of novel and
      rare mutations in HCM patients have added new data to the spectrum of gene
      mutations associated with this disease. These findings provide an essential basis
      for the molecular diagnosis and better management of family members at risk of
      familial HCM.

PMID- 28498466
TI  - Elevated SLC26A4 gene promoter methylation is associated with the risk of
      presbycusis in men.
AB  - Presbycusis affects approximately one-third of people over the age of 65 and is a
      worldwide health problem. In the current study, whether the methylation level of
      solute carrier family 26 member 4 (SLC26A4) predicted an increased risk of
      presbycusis was investigated. Peripheral blood samples from 102 patients with
      presbycusis and 104 controls were collected, and the methylation of the CpG sites
      of SLC26A4 was measured by applying pyrosequencing technology combined with
      sodium bisulfate DNA conversion chemistry. Within the SLC26A4 promoter region,
      one CpG site (CpG3) exhibited a significantly (P<0.0001) greater methylation
      level in the patients with presbycusis (26.5+/-5.56%) compared with the controls
      (23.8+/-3.85%). Significantly different CpG3 methylation levels were observed
      between the patients with presbycusis and the controls among the male
      participants (P=0.0004). In addition, a significant decrease in the
      transcriptional level of SLC26A4 in peripheral blood was observed in the patients
      with presbycusis compared with the controls. Furthermore, analyses of the
      receiver operating characteristic (ROC) curves indicated that CpG3 methylation at
      the SLC26A4 promoter predicted the risk of presbycusis in the male participants
      (AUC=0.684, 95% CI=0.584-0.784, P=0.001). The results demonstrated the
      significance of the CpG site methylation level of SLC26A4, and thus provides a
      potential marker for the diagnosis of presbycusis.

PMID- 28498467
TI  - Antibody to human alpha-fetoprotein inhibits cell growth of human hepatocellular
      carcinoma cells by resuscitating the PTEN molecule: in vitro experiments.
AB  - It has been proposed that alpha-fetoprotein (AFP) is a new member of the
      intracellular signaling molecule family of the phosphoinositide 3-kinase
      (PI3K)/AKT signaling pathway via interaction with the phosphatase and tensin
      homolog (PTEN). In this study, the effects of anti-human AFP antibody on the
      functions of PTEN were examined using an AFP-producing human hepatoma cell line.
      The antibody caused significant inhibition of cell growth, compared to a normal
      IgG control, with the accumulation of intracellular immune complexes followed by
      significant reduction of cytosolic functional AFP. Decrease in the amount of AKT
      phosphorylated on serine (S) 473 indicated that PI3K/AKT signaling was suppressed
      in the cells. S380-phosphorylated PTEN increased markedly by the second day after
      antibody treatment, with slight but significant increase in the PTEN protein
      level. Since phosphorylation at S380 is critical for PTEN stability, the increase
      in S380-phosphorylated PTEN indicated maintenance of the number of PTEN molecules
      and the related potential to control PI3K/AKT signaling. p53 protein (P53)
      significantly, but slightly increased during antibody treatment, because PTEN
      expression increased the stability and function of P53 via both molecular
      interactions. P53 phosphorylated at S20 or at S392 dramatically increased,
      suggesting an increase in the stability, accumulation and activation of P53.
      Glucose transporter 1 (GLUT1) increased immediately after antibody treatment,
      pointing to a deficiency of glucose in the cells. Immunofluorescence cytology
      revealed that antibody-treatment re-distributed GLUT1 molecules throughout the
      cytoplasm with a reduction of their patchy localization on the cell surface. This
      suggested that translocation of GLUT1 depends on the PI3K/AKT pathway, in
      particular on PTEN expression. Antibody therapy targeted at AFP-producing tumor
      cells showed an inhibitory effect on the PI3K/AKT pathway via the liberation,
      restoration and functional stabilization of PTEN. PTEN simultaneously induced
      both P53 activation and intracellular translocation of GLUT1, since these are
      closely associated with PTEN.

PMID- 28498468
TI  - MicroRNA-379-5p plays a tumor-suppressive role in human bladder cancer growth and
      metastasis by directly targeting MDM2.
AB  - Bladder cancer is the second most common urological malignancy in the US and is
      the most frequently diagnosed urological malignancy in China. An increasing
      amount of evidence indicates that microRNAs perform extremely important functions
      in many biological processes related to the formation and progression of cancers,
      including bladder cancer. Previous studies have reported that microRNA-379-5p
      (miR-379-5p) is involved in tumour initiation and development in human cancers.
      However, the expression pattern, biological functions and the underlying
      mechanisms of miR-379-5p in bladder cancer remain unknown. The present study
      demonstrated that the expression levels of miR-379-5p in bladder cancer tissues
      and cell lines were lower than the levels in adjacent normal tissues and the
      human bladder epithelial immortalized SV-HUC-1 cell line. Restoration of the
      expression of miR-379-5p inhibited bladder cancer cell proliferation, migration
      and invasion. Mouse double minute 2 (MDM2) was identified as a direct target gene
      of miR-379-5p. Furthermore, similar to miR-379-5p overexpression in bladder
      cancer cells, inhibition of MDM2 exerted tumor-suppressive effects. Rescue
      experiments showed that upregulation of MDM2 reversed the inhibitory effects of
      miR-379-5p on bladder cancer cell proliferation, migration and invasion. MDM2 was
      highly expressed and inversely correlated with miR-379-5p expression in bladder
      cancer tissues. These findings suggest that the miR-379-5p/MDM2 pathway plays an
      important role in bladder cancer and could serve as a potential candidate for
      bladder cancer therapeutics.

PMID- 28498469
TI  - Expression of c-FLIP in a rat model of sepsis and its effects on endothelial
      apoptosis.
AB  - Sepsis is characterized by the impaired regulation of inflammatory responses.
      Apoptosis is important in the pathogenesis of sepsis. Cellular FLICE-inhibitory
      protein (c-FLIP) is a catalytically inactive caspase-8 homologue, which
      negatively interferes with apoptotic signaling. The role of c-FLIP in sepsis and
      in endothelial cell apoptosis, a critical step in the pathogenesis of sepsis,
      remains controversial. In the present study, to investigate the relationship
      between c-FLIP and sepsis, a rat model of sepsis was induced by cecal ligation
      and puncture, and western blot analysis was used to detect the expression of c
      FLIPL, the long isoform of c-FLIP. Lower protein expression levels of c-FLIPL
      were found in the brain, intestine and lung of the rat sepsis model, compared
      with the rats in the sham surgery group. The association between the expression
      of c-FLIPL and endothelial cell apoptosis was further examined in vitro by c
      FLIPL overexpression and flow cytometry, which demonstrated that the expression
      of c-FLIPL was inversely correlated with endothelial cell apoptosis. These data
      suggested that c-FLIP may be important in sepsis and shed light on therapeutic
      strategies.

PMID- 28498470
TI  - Novel role of semaphorin 3A in the growth and progression of hepatocellular
      carcinoma.
AB  - Semaphorin 3A (SEMA3A), a secretory protein, is a founding member of the
      semaphorin family and functions in both the biological behavior of tumor cells
      and the modulation of tumor-associated macrophages. However, the role of SEMA3A
      in hepatocellular carcinoma (HCC) is still not well established. In the present
      study, we investigated the expression levels of SEMA3A in 80 HCC tissues and cell
      lines, using RT-qPCR, western blotting and immunohistochemistry. Expression
      profile analysis revealed that SEMA3A was significantly overexpressed in human
      HCC patients and positively correlated with the metastatic potential of HCC
      cells. Lentiviral transfection into PLC/PRF/5 and HCCLM3 cells was performed to
      stably upregulate and downregulate the expression of SEMA3A in HCC cells. Cell
      Counting Kit-8 (CCK-8), wound-healing and invasion assays revealed that SEMA3A
      promoted the proliferation and migration of HCC cells in vitro. Proteome profiler
      antibody microarray analysis revealed that overexpression of SEMA3A in HCC cells
      induced a significant increase in the expression levels of gelsolin-like capping
      protein (CapG), galectin-3, enolase 2 and epithelial cell adhesion molecule
      (EpCAM). Furthermore, the upregulation of SEMA3A in HCC cells promoted tumor
      growth and progression in an HCC mouse model. These results indicate that SEMA3A
      enhances CapG, galectin-3, enolase 2 and EpCAM expression to promote HCC
      progression and is a potential therapeutic target for HCC.

PMID- 28498471
TI  - Sodium tanshinone IIA sulfonate improves inflammation, aortic endothelial cell
      apoptosis, disseminated intravascular coagulation and multiple organ damage in a
      rat heat stroke model.
AB  - The aim of the present study was to investigate the effects of sodium tanshinone
      IIA sulfonate (STS) on inflammatory responses, aortic endothelial cell apoptosis,
      disseminated intravascular coagulation (DIC) and multiple organ damage in an
      animal model of classic heat stroke (CHS). The rats in the heat stroke (HS) and
      STS-treated heat stroke (STS-HS) groups were placed into a pre-warmed animal
      temperature controller (ATC) at 35C. The moment at which the rectal temperature
      reached 43.5C was considered as the time of onset of HS. In the HS groups, the
      rats were removed from the ATC and allowed to recover at 26C for 0, 2, 6 or 12 h.
      In the STS-HS groups, the rats received femoral vein injections of 5-40 mg/kg STS
      immediately following the onset of HS and were subsequently placed at a
      temperature of 26C to recover for 6 h. In the present study, the serum levels of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 were assessed
      using ELISA, and the numbers of apoptotic aortic endothelial cells were
      investigated using terminal deoxynucleotidyl transferase deoxyuridine
      triphosphate nick-end labeling combined with immunofluorescence. In the HS
      groups, the serum levels of TNF-alpha, IL-1beta and IL-6, as well as the numbers
      of apoptotic aortic endothelial cells were increased compared with the
      normothermic control group. Additionally, the plasma prothrombin time, activated
      partial thromboplastin time and D-dimer level were significantly increased in the
      HS group compared with the normothermic control group following recovery for 6 h.
      By contrast, the platelet count was decreased in the HS group compared with the
      normothermic control group. The serum levels of creatinine, blood urea nitrogen,
      alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and
      lactate dehydrogenase were increased and histopathological damage to multiple
      organs was observed in the HS group following recovery for 6 h. In the STS-HS
      groups, cytokine levels and apoptotic aortic endothelial cell numbers were
      reduced compared with the HS group after 6 h recovery. STS (40 mg/kg) treatment
      additionally improved the serum levels of organ injury indicators and plasma
      indicators of coagulopathy, and prevented histopathological damage to multiple
      organs. These findings demonstrated that STS treatment may ameliorate multiple
      organ damage by attenuating inflammatory responses, aortic endothelial cell
      apoptosis and DIC in CHS. These results suggested that STS may hold potential as
      an alternative therapeutic strategy for the treatment of patients with HS.

PMID- 28498472
TI  - Salinomycin induces endoplasmic reticulum stress-mediated autophagy and apoptosis
      through generation of reactive oxygen species in human glioma U87MG cells.
AB  - Salinomycin is a polyether ionophore antibiotic that has recently been shown to
      induce cell apoptosis in human cancer cells displaying multiple mechanisms of
      drug resistance. In the present study, we explored the impact of salinomycin on
      the apoptosis and autophagy as well as the correlation between those effects and
      endoplasmic reticulum (ER) stress molecular mechanisms in human glioma U87MG
      cells. Apoptosis, autophagy and reactive oxygen species (ROS) were analyzed using
      flow cytometry. In addition, expression levels of apoptosis-, autophagy- and ER
      stress-related proteins were determined by western blotting. The results showed
      that salinomycin induced apoptosis, ER stress and autophagy in glioma cancer cell
      lines. In addition, salinomycin also induced ROS generation, and the ROS
      scavenger N-acetyl-L-cysteine was found to inhibit the salinomycin-induced
      apoptosis, ER stress and autophagy. The inhibition of ER stress with 4
      phenylbutyric acid depressed salinomycin-induced apoptosis and autophagy.
      Salinomycin increased the expression of autophagy marker protein, LC3B, and
      accumulation of acidic vesicular organelles. Furthermore, pre-treatment with the
      autophagy inhibitor 3-methyladenine showed potential in increasing the apoptosis
      rate induced by salinomycin in the U87MG cells. Taken together, these results
      revealed that salinomycin induced apoptosis and autophagy via ER stress mediated
      by ROS, suggesting that ER stress by salinomycin plays a dual function in both
      promoting and suppressing cell death.

PMID- 28498473
TI  - Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the
      downregulation of anti-apoptotic proteins.
AB  - Cholangiocarcinoma (CCC) is an aggressive malignancy with poor therapeutic
      options and pronounced chemotherapy resistance. The bioactive broccoli substance,
      sulforaphane (SFN), is a promising new therapeutic option since it has been found
      to induce therapeutic effects in both experimental and epidemiological studies in
      various tumor entities. Thus, the present study was designed to assess the effect
      of SFN on cisplatin sensitivity in CCC. Human HuCCT-1 and TFK-1 cells,
      representing intrahepatic and extrahepatic CCC, respectively, were treated with
      cisplatin and SFN. Viability, the platinated DNA content, and apoptosis were
      assessed using both MTT assay and flow cytometry, while western blotting was used
      to analyze the expression of proteins involved in apoptosis and DNA damage.
      Whereas cisplatin was largely ineffective, SFN only therapy significantly
      decreased the viability of both CCC cell lines. The combination of SFN with
      cisplatin increased cisplatin cytotoxicity, which was particularly pronounced
      relatively early at 36 h after treatment. Apoptosis, which was reflected by the
      cleavage of caspase-3 and PARP, was significantly enhanced. Notably, only
      cisplatin was found to induce the expression of proteins involved in the DNA
      damage response; however, the presence of SFN appeared to enable otherwise
      cisplatin-resistant cells to undergo apoptosis. Due to the fact that SFN did not
      enhance the DNA platination levels upon cisplatin treatment, SFN may have exerted
      its activity via the inhibition of the anti-apoptotic proteins Bcl-2 and XIAP, as
      we observed. Data presented in the present study clearly demonstrated that SFN
      significantly decreased the drug resistance to cisplatin in human CCC. This
      highlights dietary co-treatment as a viable new treatment option for CCC.

PMID- 28498474
TI  - Effect of miR-1244 on cisplatin-treated non-small cell lung cancer via MEF2D
      expression.
AB  - The aim of this study was to investigate the function of miR-1244 in cisplatin
      treated non-small cell lung cancer (NSCLC). The results of quantitative PCR
      analysis revealed that the expression levels of miR-1244 in cisplatin-treated
      A549 and NCI-H522 human lung cancer cell lines were lower than those in untreated
      A549 and NCI-H522 cells. Similarly, the expression level of miR-1244 in NSCLC
      tissue samples from cisplatin-treated patients was also lower than that in non
      cisplatin-treated NSCLC patients. Notably, the overall survival times of
      cisplatin-treated NSCLC patients with high miR-1244 expression were superior to
      those patients with low miR-1244 expression. We found that overexpression of miR
      1244 suppressed cell viability and increased LDH toxicity in cisplatin-treated
      A549 and NCI-H522 cells. Additionally, overexpression of miR-1244 induced the
      apoptosis of cisplatin-treated A549 and NCI-H522 cells. Furthermore,
      overexpression of miR-1244 promoted caspase-3 activity and p53 and Bax protein
      expression, and suppressed myocyte enhancer factor 2D (MEF2D) and cyclin D1
      protein expression in cisplatin-treated A549 and NCI-H522 cells. Small
      interfering RNA (siRNA) targeting MEF2D suppressed the protein expression of
      MEF2D, and was able to decrease the proliferation, promote caspase-3 activity,
      p53 and Bax protein expression and inhibit cyclin D1 protein expression in
      cisplatin-treated A549 and NCI-H522 cells following the overexpression of miR
      1244. In summary, we found that miR-1244 affected cisplatin-treated NSCLC via
      MEF2D expression.

PMID- 28498476
TI  - Effects of unfractionated heparin and rivaroxaban on the expression of heparanase
      and fibroblast growth factor 2 in human osteoblasts.
AB  - Long-term treatment with anticoagulants may contribute to osteoporosis. Although
      unfractionated heparin and rivaroxaban have adverse effects on bone
      microstructure and function in adult rats, the underlying mechanism remains to be
      elucidated. Heparanase (HPSE) and fibroblast growth factor (FGF)2 are important
      signals in bone formation and fracture healing. Therefore, the present study was
      designed to investigate the effects of unfractionated heparin and rivaroxaban on
      the expression of HPSE and FGF2 in human osteoblasts. Human osteoblasts were
      treated with unfractionated heparin (0.5-50 IU/ml) or rivaroxaban (0.13-13 ug/ml)
      for different durations. Plasmids encoding HPSE and FGF2 were transfected into
      osteoblasts, and cell viability was assessed using MTT assays, with mRNA and
      protein expression levels determined using reverse transcription-quantitative
      polymerase chain reaction and western blot analyses, respectively. Osteoblast
      growth was significantly inhibited by treatment with unfractionated heparin (50
      IU/ml) or rivaroxaban (13 ug/ml). Unfractionated heparin alone significantly
      inhibited the expression of HPSE and FGF2, whereas rivaroxaban inhibited the
      expression of FGF2 without affecting that of HPSE. Furthermore, the
      overexpression of HPSE or FGF2 significantly reversed the inhibitory effects of
      unfractionated heparin and rivaroxaban on osteoblasts. These findings suggested
      that HPSE and FGF2 signals were involved in the detrimental role of
      unfractionated heparin and rivaroxaban in human osteoblasts, providing novel
      information on the side effects of anticoagulants.

PMID- 28498475
TI  - Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced
      cervical cancer and suppresses tumor growth.
AB  - In order to improve the sensitivity of cervical cancer cells to irradiation
      therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of
      glycolysis, and explore its role in cervical cancer cells. We suppressed HK2
      expression and/or function by shRNA and/or metformin and found HK2 inhibition
      enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase
      3. HK2 inhibition also induced much inferior proliferation of cervical cancer
      cells both in vitro and in vivo with diminishing expression of mTOR, MIB and
      MGMT. Moreover, HK2 inhibition altered the metabolic profile of cervical cancer
      cells to one less dependent on glycolysis with a reinforcement of mitochondrial
      function and an ablation of lactification ability. Importantly, cervical cancer
      cells contained HK2 inhibition displayed more sensitivity to irradiation. Further
      results indicated that HPV16 E7 oncoprotein altered the glucose homeostasis of
      cervical cancer cells into glycolysis by coordinately promoting HK2 expression
      and its downregulation of glycolysis. Taken together, our findings supported a
      mechanism whereby targeting HK2 inhibition contributed to suppress HPV16 E7
      induced tumor glycolysis metabolism phenotype, inhibiting tumor growth, and
      induced apoptosis, blocking the cancer cell energy sources and ultimately
      enhanced the sensitivity of HPV(+) cervical cancer cells to irradiation therapy.

PMID- 28498477
TI  - Identification of candidate substrates of ubiquitin-specific protease 13 using 2D
      DIGE.
AB  - The present study aimed to identify candidate substrates of ubiquitin-specific
      protease (USP)13 using two-dimensional fluorescence difference gel
      electrophoresis (2D-DIGE). USP13 is a well-characterized member of the USP
      family, which regulates diverse cellular functions by cleaving ubiquitin from
      ubiquitinated protein substrates. However, existing studies indicate that USP13
      has no detectable hydrolytic activity in vitro. This finding implies that USP13
      likely has different substrate specificity. In this study, a USP cleavage assay
      was performed using two different types of model substrates (glutathione S
      transferase-Ub52 and ubiquitin-beta-galactosidase) to detect the deubiquitinating
      enzyme (DUB) activity of USP13. In addition, a proteomic approach was taken by
      using 2D-DIGE to detect cellular proteins whose expressoin is significantly
      altered in 293T cell lines following the overexpression of USP13 or its C345S
      mutant (the catalytically inactive form). The data indicated that USP13 still has
      no detectable DUB activity in vitro nor does C345S. The results of 2D-DIGE
      demonstrated that the expression of several proteins increased or decreased
      significantly in 293T cells following the overexpression of USP13. Mass spec
      troscopy analysis of gel spots identified 7 proteins, including 4 proteins with
      an increased expression, namely vinculin, thimet oligopeptidase, cleavage and
      polyadenylation specific factor 3, and methylosome protein 50, and 3 proteins
      with a decreased expression, namely adenylosuccinate synthetase, annexin and
      phosphoglycerate mutase. In addition, in the samples of 293T cell lines after the
      overexpression of USP13 and USP13 C345S, vinculin exhibited an increased
      expression, suggesting that it may be a candidate substrate of USP13. However,
      sufficient follow-up validation studies are required in order to determine
      whether vinculin protein directly interacts with USP13.

PMID- 28498478
TI  - Demethylation of miR-495 inhibits cell proliferation, migration and promotes
      apoptosis by targeting STAT-3 in breast cancer.
AB  - In breast cancer (BC), silencing of miRNA genes due to miRNA gene promoter
      methylation are the important mechanisms directly contributing to tumorigenesis
      and tumor progression. miRNA-495 (miR-495) has been reported to be a tumor
      suppressor gene in various cancers, but its role and regulation in BC remains
      unclear. In the present study, the level of miR-495 was inversely correlated with
      the expression of STAT-3 in BC tissues and cell lines. miR-495 can directly
      target 3'-UTR of STAT-3 mRNA and thereby decrease the expression of STAT-3 in MCF
      7 and HCC1973 cells by Targetscan and Dual-luciferase assay. We further analyzed
      miR-495 promoter methylation by sodium bisulfite sequencing method (BSP), and
      found DNA methyltransferase inhibitor, 5-AzaC concomitantly upregulated
      expression of miR-495 and downregulated its target gene STAT-3 and its downstream
      target VEGF. Furthermore, we further observed that 5-AzaC treatment, miR-495
      mimics and STAT-3 knockdown significantly inhibited cell function in breast
      cancer by Transwell assay, EdU flow cytometry, Annexin V-FITC/PI combined with
      flow cytometry and Hoechst staining. Taken together, our data are first to
      demonstrate that the miR-495 is silenced due to promoter methylation in breast
      cancer. DNA methyltransferase inhibitor 5-AzaC could reverse miR-495 (suppressor
      gene) and STAT-3 (oncogene). The anticancer properties of 5-AzaC were
      preliminarily confirmed in breast cancer.

PMID- 28498479
TI  - PPAR-alpha improves the recovery of lung function following acute respiratory
      distress syndrome by suppressing the level of TGF-beta1.
AB  - Although peroxisome proliferator-activated receptor (PPAR)-alpha has been
      reported to be involved in preventing acute lung injury (ALI), the molecular
      regulation of post-ALI lung recovery remains to be fully elucidated. The aim of
      the present study was to characterize the mechanism by which PPAR-alpha prevents
      ALI and examine the role of PPAR-alpha in the recovery of lung function following
      acute respiratory distress syndrome (ARDS). Reverse transcription-quantitative
      polymerase chain reaction and western blot analyses suggested that PPAR-alpha was
      effective in suppressing transforming growth factor (TGF)-beta1 in HLF cells and
      RAW 264.7 cells. In an ALI mouse model, PPAR-alpha treatment prior to stimulation
      with lipopolysaccharide (LPS) resulted in a decrease in the expression of TGF
      beta1 in bronchoalveolar lavage fluid (BALF), peripheral blood and splenocytes.
      The injection of a virus expressing short hairpin PPAR-alpha into mice following
      LPS treatment resulted in a dose-dependent increase in lung resistance index and
      decrease in dynamic compliance, and a significant increase in BALF protein, which
      indicated PPAR-alpha was essential for the recovery of lung function following
      ALI. Of note, the serum expression of PPAR-alpha was inversely correlated with
      TGF-beta1 and negatively correlated with disease severity in patients with ARDS.
      These data suggested that PPAR-alpha was essential for the recovery of lung
      function following ALI by the suppression of TGF-beta1, which reveals a
      previously unappreciated mechanism controlling post-ALI lung recovery.

PMID- 28498480
TI  - Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial
      mediated pathways in human bladder cancer cells.
AB  - Miconazole (MIC), an antifungal agent, diplays anti-tumorigenic activity in
      various types of human cancers, including bladder cancer, yet its mechanism of
      antitumor action is not well understood. In the present study, we demonstrated
      that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and
      TSGH-8301 bladder cancer cells in a dose- and time-dependent manner, but did not
      exhibit significant toxicity toward human peripheral blood mononuclear cells.
      Cell cycle analysis revealed that MIC at concentrations of 25 and 50 uM
      significantly caused G0/G1 arrest in the TSGH-8301 and T24 cells, respectively.
      DNA fragmentation, mitochondrial membrane potential and western blot analyses
      showed that MIC inhibited the growth of these cells by both mitochondrial
      mediated and death receptor (DR5)-mediated apoptosis pathways. Specifically, MIC
      increased the protein levels of p21 and p27, but decreased the expression of
      cyclin E1, CDK2 and CDK4. MIC augmented the expression of DR5, cleaved forms of
      caspase-3 -8 and -9, poly(ADP-ribose) polymerase and Bax, decreased the
      expression of Bcl-2 but increased cytosol levels of cytochrome c. Our results
      suggest that MIC inhibits the growth of bladder cancer cells through induction of
      G0/G1 arrest and apoptosis via activation of both the extrinsic and intrinsic
      apoptotic pathways. MIC is a potential chemotherapeutic agent for treating
      bladder cancer in humans.

PMID- 28498482
TI  - Effects of an antenatal lifestyle intervention on offspring obesity - a 5-year
      follow-up of a randomized controlled trial.
AB  - INTRODUCTION: Strategies to limit excessive maternal gestational weight gain
      could also have positive health effects for the offspring. This study informs us
      on the effect of an antenatal lifestyle intervention on offspring body mass index
      (BMI) trajectory until age five. MATERIAL AND METHODS: A secondary analysis of a
      randomized controlled trial aimed at reducing gestational weight gain, set in
      Orebro, Sweden (Clinical Trials.gov Id NCT00451425). Offspring were followed with
      standardized measures of weight and height until age five. Mean BMI z-score and
      proportion (%) of over- and undernutrition (BMI z-score > +/- 2 standard
      deviations) was compared between groups. Risk estimates for obesity at age five
      were analyzed in relation to maternal gestational weight gain and prepregnancy
      BMI as a secondary outcome. RESULTS: We analyzed 374 children at birth and 300 at
      age five. No significant difference in mean BMI z-score was seen at birth (0.68
      (I) vs 0.56 (C), p = 0.242) or at age five (0.34 (I) vs 0.26 (C), p = 0.510) and
      no significant difference in proportion of over- or undernutrition was seen.
      Excessive maternal gestational weight gain was an independent risk factor for
      offspring obesity at birth (OR = 4.51, p < 0.001) but not at age five. Maternal
      obesity was an independent risk factor for offspring obesity at age five (OR =
      4.81, p = 0.006). CONCLUSIONS: Our composite antenatal lifestyle intervention did
      not significantly reduce the risk of obesity in offspring up until age five.

PMID- 28498481
TI  - Comparison of three different methods for the detection of circulating tumor
      cells in mice with lung metastasis.
AB  - Circulating tumor cells (CTCs) represent the key step of cancer cell
      dissemination. The alteration of CTCs correlates with the treatment outcome and
      prognosis. To enrich and identify CTCs from billions of blood cells renders a
      very challenging task, which triggers development of several methods, including
      lysis of RBC plus negative or positive enrichment using antibodies, and filter
      membrane or spiral microfluidics to capture CTCs. To compare the advantages of
      different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells
      transfected with both green fluorescent protein (GFP) and luciferase to trace
      CTCs in the experimental lung metastasis model. Three methods were used to detect
      CTCs at the same time: bioluminescence assay, smearing method, and membrane
      filter method. The in vivo alive mouse imaging was used to dynamically monitor
      the growth of lung metastases. The sensitivity and accuracy of three detection
      methods were compared side-by-side. Our results showed that 1) the sensitivity of
      bioluminescence assay was the highest, but there was no information of CTC
      morphology; 2) the smearing method and membrane filter method could observe the
      detail of CTC morphology, such as in single or in cluster, while their
      sensitivity was lower than bioluminescence assay; 3) A dynamic observation at a 7
      day intervals, the lung metastatic cancer grew at a log speed, while CTCs were
      increased at a low speed. This might be due to the activated immune cells
      eliminating the CTCs at a speed much faster than CTCs were generated. This
      comparison of three CTC detection methods in mouse model suggests that
      bioluminescence assay could be used in quantitative study of the effect of
      certain agent on the suppression of CTCs, while GFP-based morphological assays
      could be used to study the dissemination mechanism of CTCs. The combination of
      both bioluminescence assay and GFP-based assay would generate more information
      for quantity and quality of CTCs.

PMID- 28498483
TI  - Reflectance confocal microscopy in the evaluation of targetoid haemosiderotic
      haemangioma apropos two cases.

PMID- 28498484
TI  - Sinkholes Due to Groundwater Withdrawal in Tazerbo Wellfield, SE Libya.
AB  - The desert of eastern Libya forms one of the most arid regions of the Sahara. The
      Great Man-Made River Project (GMRP) was established. It transports millions of
      cubic meters of water a day from desert wellfields to the coastal cities, where
      over 80% of the population lives. The Tazerbo Wellfield is one of the wellfields
      designed within the GMRP, delivering water to the eastern coast of Libya through
      an underground pipe network. Tazerbo Wellfield consists of 108 production wells;
      each well was designed to pump 100 L/s. The planned total groundwater withdrawal
      from all wells is 1 million m3 /d. The deep sandstone aquifer (Nubian sandstone)
      is covered by a thick mudstone-siltstone aquitard and is being heavily pumped.
      The aquifer and fine-grained sediments of the aquitard may be compacted resulting
      in land subsidence as a result of high exploitation. Local sinkholes have
      developed in the area of Tazerbo since the start of the pumping from the
      wellfield in 2004. These sinkholes have been caused mainly by lowering of the
      piezometric heads due to the withdrawal of groundwater. In this study, a
      hydrogeological investigation is presented about the effect of large groundwater
      pumping from the Nubian sandstone aquifer in Tazerbo Wellfield, SE Libya, based
      on physical parameters for 108 production wells and 23 observation wells.

PMID- 28498485
TI  - Transient Recharge Estimability Through Field-Scale Groundwater Model
      Calibration.
AB  - The estimation of recharge through groundwater model calibration is hampered by
      the nonuniqueness of recharge and aquifer parameter values. It has been shown
      recently that the estimability of spatially distributed recharge through
      calibration of steady-state models for practical situations (i.e., real-world,
      field-scale aquifer settings) is limited by the need for excessive amounts of
      hydraulic-parameter and groundwater-level data. However, the extent to which
      temporal recharge variability can be informed through transient model
      calibration, which involves larger water-level datasets, but requires the
      additional consideration of storage parameters, is presently unknown for
      practical situations. In this study, time-varying recharge estimates, inferred
      through calibration of a field-scale highly parameterized groundwater model, are
      systematically investigated subject to changes in (1) the degree to which
      hydraulic parameters including hydraulic conductivity (K) and specific yield (Sy
      ) are constrained, (2) the number of water-level calibration targets, and (3) the
      temporal resolution (up to monthly time steps) at which recharge is estimated.
      The analysis involves the use of a synthetic reality (a reference model) based on
      a groundwater model of Uley South Basin, South Australia. Identifiability
      statistics are used to evaluate the ability of recharge and hydraulic parameters
      to be estimated uniquely. Results show that reasonable estimates of monthly
      recharge (<30% recharge root-mean-squared error) require a considerable amount of
      transient water-level data, and that the spatial distribution of K is known.
      Joint estimation of recharge, Sy and K, however, precludes reasonable inference
      of recharge and hydraulic parameter values. We conclude that the estimation of
      temporal recharge variability through calibration may be impractical for real
      world settings.

PMID- 28498486
TI  - The authors respond.

PMID- 28498487
TI  - The malleus to oval window revision stapedotomy: Efficacy and longitudinal study
      outcome.
AB  - OBJECTIVE: To determine the longitudinal effectiveness of the malleus to oval
      window stapedotomy technique among patients undergoing revision surgery when the
      incus is unavailable. STUDY DESIGN: Retrospective, case series. METHODS: Charts
      of 15 patients who underwent 17 malleus attachment stapedotomies performed by a
      single surgeon from 2000 to 2015 were reviewed. Surgery was ambulatory,
      transcanal, with laser technique, and under local anesthesia. RESULTS: Of 17
      stapedotomies performed, there were nine first revisions, six second revisions,
      one third revision, and one fourth revision. There were no surgical
      complications. Mean preoperative air-bone gap (ABG) was 32.3 dB. Mean
      postoperative ABG at 6 months was 10.7 dB, and at last follow-up was 16.3 dB.
      Average length of follow-up was 36.5 months. At last follow-up, 100% of first
      revisions achieved ABG <= 20 dB (77.8% <= 10 dB), compared to 50% of second
      revisions with ABG <= 20 dB (none <= 10 dB), and 0% of third or fourth revisions
      with ABG <= 20 dB. Trend lines for second and third/fourth revisions showed a
      deterioration (widening) in postoperative ABG by 0.18 and 0.72 dB per month,
      respectively. The first-revision trend line, conversely, showed negligible change
      with time, demonstrating the superior durability of first revisions compared to
      subsequent surgeries. CONCLUSION: The malleus to oval window stapedotomy
      technique is more effective and longer lasting in first-revision surgery compared
      to subsequent procedures. Standard or implantable amplification devices may be
      preferable for patients with multiple prior procedures. LEVEL OF EVIDENCE: 4.
      Laryngoscope, 128:461-467, 2018.

PMID- 28498488
TI  - Slotted labyrinthotomy approach with customized electrode for patients with
      common cavity deformity.
AB  - OBJECTIVES/HYPOTHESIS: Cochlear implantation for patients with common cavity
      deformity (CCD) can be difficult, with a higher incidence of intra- and
      postoperative complications; outcomes with CCD patients are also highly variable.
      In this study, surgical time was compared between the traditional facial recess
      approach (TFRA) and the transmastoid slotted labyrinthotomy approach (TSLA).
      Audiological outcomes and the benefit of using customized electrode arrays for
      CCD patients are also discussed. STUDY DESIGN: Retrospective review of 13
      cochlear implant (CI) patients with CCD. METHODS: Six patients were implanted
      with the TFRA using traditional electrodes, and seven patients were implanted
      with the TSLA using customized electrodes. Intra- and postoperative complications
      were reviewed. Audiological outcomes were measured 3 months to 2 years after CI
      activation. RESULTS: The mean surgical time for TSLA group was nearly half as
      long as for the TRFA group (P < .05). Although mean audiological outcomes were
      better for the TSLA group, there was no significant difference between groups (P
      > .05). CONCLUSIONS: For CCD patients, TSLA for cochlear implantation is
      recommended due to shortened surgical time; customized electrode arrays may be
      additionally advantageous in terms of audiological outcomes. LEVEL OF EVIDENCE:
      4. Laryngoscope, 128:468-472, 2018.

PMID- 28498489
TI  - Application of Edible Films Containing Oregano (Origanum vulgare) Essential Oil
      on Queso Blanco Cheese Prepared with Flaxseed (Linum usitatissimum) Oil.
AB  - Fortification of queso blanco (QB) with flaxseed oil (FO) containing omega-3
      polyunsaturated fatty acids may provide a functional food with health benefits
      such as improved cell, brain, and retina functionality, and protection against
      cardiovascular and immune-inflammatory diseases. However, QB experiences a short
      shelf life because of the early development of yeasts and molds and addition of
      FO may increase susceptibility to lipid oxidation. Oregano essential oil (OEO) is
      known for its antimicrobial and antioxidant properties, but due to its intense
      flavor compounds it may not be suitable for direct incorporation into QB. Thus,
      incorporation of OEO into an edible film prepared with whey protein isolate (WPI)
      may improve the shelf life of QB. Scanning electron microscopy (SEM) micrographs
      revealed that FO was successfully retained by the cheese after homogenization.
      The thiobarbituric-acid-reactive-substances (TBARS) and yeast and mold counts
      (YMC) of the wrapped cheeses were analyzed during 60 d of refrigerated storage.
      The oxidation rate increased significantly for nonwrapped QB containing FO (QBFO)
      during storage, however wrapping with WPI edible films containing OEO (WOF)
      significantly limited lipid oxidation and prevented growth of yeasts and molds.
      This study demonstrated the antioxidant and antimicrobial properties of WOF for
      preservation of QBFO during refrigerated storage.

PMID- 28498490
TI  - Multi-subgroup gene screening using semi-parametric hierarchical mixture models
      and the optimal discovery procedure: Application to a randomized clinical trial
      in multiple myeloma.
AB  - This article proposes an efficient approach to screening genes associated with a
      phenotypic variable of interest in genomic studies with subgroups. In order to
      capture and detect various association profiles across subgroups, we flexibly
      estimate the underlying effect size distribution across subgroups using a semi
      parametric hierarchical mixture model for subgroup-specific summary statistics
      from independent subgroups. We then perform gene ranking and selection using an
      optimal discovery procedure based on the fitted model with control of false
      discovery rate. Efficiency of the proposed approach, compared with that based on
      standard regression models with covariates representing subgroups, is
      demonstrated through application to a randomized clinical trial with microarray
      gene expression data in multiple myeloma, and through a simulation experiment.

PMID- 28498491
TI  - The blood cell family on a lymph node road.

PMID- 28498492
TI  - Multiple roles of afadin in the ultrastructural morphogenesis of mouse
      hippocampal mossy fiber synapses.
AB  - A hippocampal mossy fiber synapse, which is implicated in learning and memory,
      has a complex structure in which mossy fiber boutons attach to the dendritic
      shaft by puncta adherentia junctions (PAJs) and wrap around a multiply-branched
      spine, forming synaptic junctions. Here, we electron microscopically analyzed the
      ultrastructure of this synapse in afadin-deficient mice. Transmission electron
      microscopy analysis revealed that typical PAJs with prominent symmetrical plasma
      membrane darkening undercoated with the thick filamentous cytoskeleton were
      observed in the control synapse, whereas in the afadin-deficient synapse,
      atypical PAJs with the symmetrical plasma membrane darkening, which was much less
      in thickness and darkness than those of the control typical PAJs, were observed.
      Immunoelectron microscopy analysis revealed that nectin-1, nectin-3, and N
      cadherin were localized at the control typical PAJs, whereas nectin-1 and nectin
      3 were localized at the afadin-deficient atypical PAJs to extents lower than
      those in the control synapse and N-cadherin was localized at their nonjunctional
      flanking regions. These results indicate that the atypical PAJs are formed by
      nectin-1 and nectin-3 independently of afadin and N-cadherin and that the typical
      PAJs are formed by afadin and N-cadherin cooperatively with nectin-1 and nectin
      3. Serial block face-scanning electron microscopy analysis revealed that the
      complexity of postsynaptic spines and mossy fiber boutons, the number of spine
      heads, the area of postsynaptic densities, and the density of synaptic vesicles
      docked to active zones were decreased in the afadin-deficient synapse. These
      results indicate that afadin plays multiple roles in the complex ultrastructural
      morphogenesis of hippocampal mossy fiber synapses.

PMID- 28498493
TI  - Involvement of microglia in early axoglial alterations of the optic nerve induced
      by experimental glaucoma.
AB  - Glaucoma is a leading cause of blindness, characterized by retinal ganglion cell
      (RGC) loss and optic nerve (ON) damage. Cumulative evidence suggests glial cell
      involvement in the degeneration of the ON and RGCs. We analyzed the contribution
      of microglial reactivity to early axoglial alterations of the ON in an induced
      model of ocular hypertension. For this purpose, vehicle or chondroitin sulfate
      (CS) were weekly injected into the eye anterior chamber from Wistar rats for
      different intervals. The amount of Brn3a(+) RGC significantly decreased in CS
      injected eyes for 10 and 15 (but not 6) weeks. A reduction in anterograde
      transport of beta-subunit cholera toxin was observed in the superior colliculus
      and the lateral geniculate nucleus contralateral to CS-injected eyes for 6 and 15
      weeks. A disruption of cholera toxin beta-subunit transport was observed at the
      proximal myelinated ON. A significant decrease in phosphorylated neurofilament
      heavy chain immunoreactivity, an increase in ionized calcium-binding adaptor
      molecule 1(+), ED1(+) (microglial markers), and glial fibrillary acidic protein
      (astrocytes) (+) area, and decreased luxol fast blue staining were observed in
      the ON at 6 and 15 weeks of ocular hypertension. Microglial reactivity
      involvement was examined through a daily treatment with minocycline (30 mg/kg,
      i.p.) for 2 weeks, after 4 weeks of ocular hypertension. Minocycline prevented
      the increase in ionized calcium-binding adaptor molecule 1(+), ED-1(+), and glial
      fibrillary acidic protein(+) area, the decrease in phosphorylated neurofilament
      heavy-chain immunoreactivity and luxol fast blue staining, and the deficit in
      anterograde transport induced by 6 weeks of ocular hypertension. Thus, targeting
      microglial reactivity might prevent early axoglial alterations in the
      glaucomatous ON. Cover Image for this issue: doi: 10.1111/jnc.13807.

PMID- 28498494
TI  - A Mercaptoacetamide-Based Class II Histone Deacetylase Inhibitor Suppresses Cell
      Migration and Invasion in Monomorphic Malignant Human Glioma Cells by Inhibiting
      FAK/STAT3 Signaling.
AB  - Histone deacetylase inhibitors (HDACIs) have emerged as potential anticancer
      agents for the treatment of solid and hematopoietic cancers. Several HDACIs delay
      cell growth, induce differentiation, or activate apoptosis in multiple types of
      tumors, including glioblastomas. In the present study, we showed that the
      mercaptoacetamide-based HDACI W2 inhibits cell migration and invasion in
      monomorphic malignant human glioma cells. W2 treatment significantly decreased
      the activity and expression levels of matrix metalloprotease-2 in malignant A172
      cells but not in U373MG cells. Key signaling pathways involved in cell migration
      and invasion, including PI3K-AKT, ERK-JNK-P38, and FAK/STAT3, were examined to
      identify the mechanism of action of W2. W2 increased the phosphorylation of AKT
      and altered cell migration and invasion in an AKT-independent manner. W2
      inhibited the phosphorylation of FAK/STAT3, and treatment with a FAK/STAT3
      inhibitor significantly suppressed cancer cell migration and MMP-2 activity in
      the presence of W2. In addition, W2 significantly inhibited the nuclear
      translocation of phospho-STAT3. Taken together, our results suggest that W2
      suppresses cancer cell migration and invasion by inhibiting FAK/STAT3 signaling
      and STAT3 translocation to the nucleus in monomorphic malignant human glioma
      cells. J. Cell. Biochem. 118: 4672-4685, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28498495
TI  - Oleaginous yeasts: Promising platforms for the production of oleochemicals and
      biofuels.
AB  - Oleaginous yeasts have a unique physiology that makes them the best suited hosts
      for the production of lipids, oleochemicals, and diesel-like fuels. Their high
      lipogenesis, capability of growing on many different carbon sources (including
      lignocellulosic sugars), easy large-scale cultivation, and an increasing number
      of genetic tools are some of the advantages that have encouraged their use to
      develop sustainable processes. This mini-review summarizes the metabolic
      engineering strategies developed in oleaginous yeasts within the last 2 years to
      improve process metrics (titer, yield, and productivity) for the production of
      lipids, free fatty acids, fatty acid-based chemicals (e.g., fatty alcohols, fatty
      acid ethyl esters), and alkanes. During this short period of time, tremendous
      progress has been made in Yarrowia lipolytica, the model oleaginous yeast, which
      has been engineered to improve lipid production by different strategies including
      increasing lipogenic pathway flux and biosynthetic precursors, and blocking
      degradation pathways. Moreover, remarkable advances have also been reported in
      Rhodosporidium toruloides and Lipomyces starkey despite the limited genetic tools
      available for these two very promising hosts. Biotechnol. Bioeng. 2017;114: 1915
      1920. (c) 2017 Wiley Periodicals, Inc.

PMID- 28498496
TI  - The author responds.

PMID- 28498497
TI  - The aggravation of arthritis by periodontitis is dependent of IL-17 receptor A
      activation.
AB  - AIM: To evaluate whether Porphyromonas gingivalis-induced periodontitis
      aggravates the antigen-induced arthritis (AIA) model, and whether this effect is
      dependent on the Th17/IL-17 signalling pathway. MATERIALS AND METHODS: Antigen
      induced arthritis was triggered by local injection of methylated bovine serum
      albumin into the knee joint of previously immunized C57BL/6 wild-type (WT) and IL
      17 receptor A (IL-17RA)-knockout mice. Periodontal disease in naive or arthritic
      mice was induced by oral infection with P. gingivalis. Animals were sacrificed 7,
      15 and 30 days after infection. Alveolar bone loss, joint histopathology,
      articular hyperalgesia and joint cytokine production were assessed, in addition
      to the proportion of Th17 and Treg cells isolated from the inguinal lymph nodes.
      RESULTS: No influence of experimentally-induced arthritis was found on the
      alveolar bone resorption induced by P. gingivalis. However, mice with
      experimentally-induced arthritis that were exposed to P. gingivalis presented
      higher joint damage and Th17 frequencies when compared to non-infected mice. The
      aggravation of arthritis by periodontitis was accompanied by increased TNF and IL
      17 production and articular neutrophil infiltration, whereas arthritis
      aggravation and changes in neutrophil infiltration were absent in IL-17RA
      deficient mice. CONCLUSION: The effects of P. gingivalis-induced periodontitis on
      arthritis are dependent on Th17 expansion and IL-17RA signalling, which lead to
      increased neutrophil infiltration into the joints.

PMID- 28498498
TI  - Impact of prescription drug monitoring programs (PDMPs) on opioid utilization
      among Medicare beneficiaries in 10 US States.
AB  - BACKGROUND AND AIMS: Prescription Drug Monitoring Programs (PDMPs) are a
      principal strategy used in the United States to address prescription drug abuse.
      We (1) compared opioid use pre- and post-PDMP implementation and (2) estimated
      differences of PDMP impact by reason for Medicare eligibility and plan type.
      DESIGN: Analysis of opioid prescription claims in US states that implemented
      PDMPs relative to non-PDMP states during 2007-12. SETTING: Florida, Louisiana,
      Nebraska, New Jersey, Vermont, Georgia, Wisconsin, Maryland, New Hampshire and
      Arkansas, USA. PARTICIPANTS: A total of 310 105 disabled and older adult Medicare
      enrolees. MEASUREMENTS: Primary outcomes were monthly total opioid volume, mean
      daily morphine milligram equivalent (MME) dose per prescription and number of
      opioid prescriptions dispensed. The key predictors were PDMP status and time.
      Tests for moderation examined PDMP impact by Medicare eligibility (disability
      versus age) and drug plan [privately provided Medicare Advantage (MAPD) versus
      fee-for-service (PDP)]. FINDINGS: Overall, PDMP implementation was associated
      with reduced opioid volume [-2.36 kg/month, 95% confidence interval (CI) = -3.44,
      -1.28] and no changes in mean MMEs or opioid prescriptions 12 months after
      implementation compared with non-PDMP states. We found evidence of strong
      moderation effects. In PDMP states, estimated monthly opioid volumes decreased
      1.67 kg (95% CI = -2.38, -0.96) and 0.75 kg (95% CI = -1.32, -0.18) among
      disabled and older adults, respectively, and 1.2 kg, regardless of plan type. MME
      reductions were 3.73 mg/prescription (95% CI = -6.22, -1.24) in disabled and 3.02
      mg/prescription (95% CI = -3.86, -2.18) in MAPD beneficiaries, but there were no
      changes in older adults and PDP beneficiaries. Dispensed prescriptions increased
      259/month (95% CI = 39, 479) among the disabled and decreased 610/month (95% CI =
      -953, -257) among MAPD beneficiaries. CONCLUSIONS: Prescription drug monitoring
      programs (PDMPs) are associated with reductions in opioid use, measured by
      volume, among disabled and older adult Medicare beneficiaries in the United
      States compared with states that do not have PDMPs. PDMP impact on daily doses
      and daily prescriptions varied by reason for eligibility and plan type. These
      findings cannot be generalized beyond the 10 US states studied.

PMID- 28498499
TI  - Heterogeneous extracellular dopamine regulation in the subregions of the
      olfactory tubercle.
AB  - Recent studies show that dense dopamine (DA) innervation from the ventral
      tegmental area to the olfactory tubercle (OT) may play an important role in
      processing multisensory information pertaining to arousal and reward, yet little
      is known about DA regulation in the OT. This is mainly due to the anatomical
      limitations of conventional methods of determining DA dynamics in small
      heterogeneous OT subregions located in the ventral most part of the brain.
      Additionally, there is increasing awareness that anteromedial and anterolateral
      subregions of the OT have distinct functional roles in natural and
      psychostimulant drug reinforcement as well as in regulating other types of
      behavioral responses, such as aversion. Here, we compared extracellular DA
      regulation (release and clearance) in three subregions (anteromedial,
      anterolateral, and posterior) of the OT of urethane-anesthetized rats, using in
      vivo fast-scan cyclic voltammetry following electrical stimulation of ventral
      tegmental area dopaminergic cell bodies. The neurochemical, anatomical, and
      pharmacological evidence confirmed that the major electrically evoked
      catecholamine in the OT was DA across both its anteroposterior and mediolateral
      extent. While both D2 autoreceptors and DA transporters play important roles in
      regulating DA evoked in OT subregions, DA in the anterolateral OT was regulated
      less by the D2 receptors when compared to other OT subregions. Comparing previous
      data from other DA rich ventral striatum regions, the slow DA clearance across
      the OT subregions may lead to a high extracellular DA concentration and
      contribute towards volume transmission. These differences in DA regulation in the
      terminals of OT subregions and other limbic structures will help us understand
      the neural regulatory mechanisms of DA in the OT, which may elucidate its
      distinct functional contribution in the ventral striatum towards mediating
      aversion, reward and addiction processes.

PMID- 28498500
TI  - Socioeconomic disparities and comorbidities, not race, affect salivary gland
      malignancy survival outcomes.
AB  - OBJECTIVES/HYPOTHESIS: This study sought to determine whether comorbidities,
      race, and socioeconomic factors affect 5- and 10-year survival outcomes for
      patients with salivary gland malignancies treated at a single large academic
      institution with a large African American population. STUDY DESIGN: A
      retrospective cohort study was performed of all patients with salivary gland
      malignancies, from 1990 to 2015, at a large academic medical center. METHODS:
      Standard statistical analysis was performed using Kaplan-Meier survival curve
      analysis and Cox proportional hazard models. RESULTS: The overall 5- and 10-year
      survival rates decreased with age >= 60 years (P < .001), stage 3 or 4 (P <
      .001), clinical T stage 3 or 4 (P < .001), and clinical N stage 1, 2, or 3 (P <
      .001). Living in a ZIP code with an increasing proportion of residents with a
      high school degree or less (P < .05), being male (P < .05), increasing age at the
      time of diagnosis (P < .001), and increasing Charlson comorbidity index (P < .05)
      detrimentally impacted survival at 5 and 10 years. Race was associated with
      socioeconomic variables, but race was not a prognostic indicator of survival.
      CONCLUSIONS: Socioeconomic factors and comorbidities, not race, were negative
      prognostic indicators of survival of patients with salivary gland malignancies.
      Using race as a marker for socioeconomic status should be used with caution.
      LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2545-2550, 2017.

PMID- 28498502
TI  - Real-time three-dimensional jaw tracking in temporomandibular disorders.
AB  - When a dysfunction occurs in any component of the stomatognathic system,
      temporomandibular disorders (TMD) may originate. The aim of this study was to
      compare the deviations, displacement and the execution speed of mandibular
      movements among asymptomatic participants and those with TMD. Convenience
      sampling was used; forty participants diagnosed by clinical evaluation following
      the Research Diagnostic Criteria for Temporomandibular Disorders were divided
      into three groups: arthropathy (GART, 10 participants, 40% men), myopathy (GMYO,
      10 participants, 30% men), and the control group (CG, 20 asymptomatic
      participants, 25% men). Participants were asked to perform the movements of free
      maximal mouth opening and closing, right and left lateral excursions, and
      protrusion with sliding teeth contacts. The mandibular trajectory was recorded
      using opto-electronic devices tracking reflective markers placed in front of the
      'soft tissue pogonion point'. The movements were analysed on the following axis:
      x - medial-lateral, y - vertical, z - antero-posterior. Significative differences
      were found in CGxGART - unassisted maximal mouth opening and closing projection
      on y-axis (OCY), CGxGMYO - unassisted maximal mouth opening and closing
      projection on x-axis (OCX), and in the measures Opening lateral deviation on x
      axis (OLDX), closing lateral deviation on x-axis (CLDX) and in the measures of
      speed for both. In regard to GARTxGMYO, a significative difference was found in
      Protrusion lateral deviation on x-axis (PLDX) 'Conover-Iman Test of Multiple
      Comparisons Using Rank Sums' using Bonferroni correction (P < 0.05). In
      conclusion, the total opening movements in individuals with TMD tended to have
      higher deviation than in those asymptomatic individuals and a reduction in the
      speed of movements.

PMID- 28498501
TI  - PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter
      integrity in patients with primary cocaine use disorder: a double-blind
      randomized controlled pilot trial.
AB  - BACKGROUND AND AIMS: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a
      promising candidate treatment for cocaine use disorder (CUD). We tested the
      effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain
      white matter (WM) integrity. Feasibility, medication compliance and tolerability
      were evaluated. DESIGN: Two-arm double-blind randomized controlled proof-of
      concept pilot trial of PIO or placebo (PLC). SETTING: Single-site out-patient
      treatment research clinic in Houston, TX, USA. PARTICIPANTS: Thirty treatment
      seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10
      = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post
      treatment. INTERVENTION: Study medication was dispensed at thrice weekly visits
      along with once-weekly cognitive behavioral therapy for 12 weeks. MEASUREMENTS:
      Measures of target engagement mechanisms of interest included cocaine craving
      assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive
      Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity.
      Feasibility measures included number completing treatment, medication compliance
      (riboflavin detection) and tolerability (side effects, serious adverse events).
      FINDINGS: Target engagement change in mechanisms of interest, defined as a >=
      0.75 Bayesian posterior probability of an interaction existing favoring PIO over
      PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed
      by fractional anisotropy (FA) values. Outcomes indicated greater decrease in
      craving and greater increase in FA values in the PIO group. Feasibility was
      demonstrated by high completion rates among those starting treatment (21/26 =
      80%) and medication compliance (>= 80%). There were no reported serious adverse
      events for PIO. CONCLUSIONS: Compared with placebo, patients receiving
      pioglitazone show a higher likelihood of reduced cocaine craving and improved
      brain white matter integrity as a function of time in treatment. Pioglitazone
      shows good feasibility as a treatment for cocaine use disorder.

PMID- 28498504
TI  - Varenicline versus nicotine patch with brief advice for smokers with substance
      use disorders with or without depression: effects on smoking, substance use and
      depressive symptoms.
AB  - AIMS: Varenicline was compared with transdermal nicotine (NRT) for smokers with
      current substance use disorders (SUD) for effects on 3-month smoking abstinence
      (primary outcome) and, secondarily, on 3- and 6 month abstinence while adjusting
      for medication adherence, and on additional smoking and substance use outcomes.
      Moderation by major depressive disorder history (MDD) and adherence were
      investigated. DESIGN: Double-blind double-placebo-controlled randomized design,
      stratifying by MDD, gender and nicotine dependence, with 3 and 6 months follow
      up. SETTING: University offices in Rhode Island, USA. PARTICIPANTS: Adult smokers
      (n = 137), in SUD treatment, substance abstinent <12 months (n = 77 varenicline,
      60 NRT). INTERVENTION AND COMPARATOR: Twelve weeks of varenicline (2 mg/day,
      after 1-week dose run-up) or NRT (21 mg/day decreasing to 7 mg/day).
      MEASUREMENTS: Primary: point-prevalence smoking abstinence (7-day, confirmed) at
      3 months. Secondary: point-prevalence abstinence at 6 months, quantity and
      frequency of smoking and substance use at 3 and 6 months, and within-treatment
      abstinence, medication adherence and depressive symptoms. Smoking outcome
      analyses were repeated controlling for adherence and investigating adherence as a
      moderator. FINDINGS: Effects on 3-month abstinence were P < 0.065 without a
      covariate (Bayes factor 3.35, supporting the effect strongly) and differed
      significantly when controlling for baseline smoking [varenicline: 13%, NRT: 3%;
      odds ratio (OR) = 4.81, 95% confidence interval (CI) 1.00, 23.13, P < 0.05]. The
      threefold difference at 6 months was not significant. Medication effect on
      abstinence across time was significant (P < 0.05) covarying adherence and
      baseline smoking (OR = 6.40, 95% CI = 1.00, 40.93). Medication differences in 3
      month abstinence occurred among participants with >= 77% adherence (P < 0.02). No
      significant medication effects on heavy drinking, drug use or depressive symptoms
      were found. CONCLUSIONS: Varenicline appears to improve the chances of achieving
      at least 3 months of smoking abstinence in smokers with substance use disorders
      trying to stop, compared with transdermal nicotine patches, the effect being
      independent of history of depressive disorder.

PMID- 28498503
TI  - p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1
      NF-kappaB pathway in human ovarian cancer cells.
AB  - Platinum-based therapeutic strategies have been widely used in ovarian cancer
      treatment. However, drug resistance has greatly limited therapeutic efficacy.
      Recently, tolerance to cisplatin has been attributed to other factors unrelated
      to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub
      participating in tumorigenesis and may be a therapeutic target. Our previous
      study showed that p62 was overexpressed in drug-resistant ovarian epithelial
      carcinoma and its inhibition increased the sensitivity to cisplatin. In this
      study, we demonstrate that the activity of the NF-kappaB signaling pathway and
      K63-linked ubiquitination of RIP1 was higher in cisplatin-resistant ovarian
      (SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance
      could be reversed by inhibiting the expression of p62 using siRNA. Furthermore,
      deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly
      decreased K63-linked ubiquitination of RIP1 and inhibited the activation of the
      NF-kappaB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor
      proliferative capacity and high levels of apoptosis in SKOV3 cells and made them
      more sensitive to cisplatin treatment. Collectively, we provide evidence that p62
      is implicated in the activation of NF-kappaB signaling that is partly dependent
      on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating
      drug resistance in ovarian cancer cells.

PMID- 28498505
TI  - Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical
      phenotype.
AB  - Frontometaphyseal dysplasia (FMD) is caused by gain-of-function mutations in the
      X-linked gene FLNA in approximately 50% of patients. Recently we characterized an
      autosomal dominant form of FMD (AD-FMD) caused by mutations in MAP3K7, which
      accounts for the condition in the majority of patients who lack a FLNA mutation.
      We previously also described a patient with a de novo variant in TAB2, which we
      hypothesized was causative of another form of AD-FMD. In this study, a cohort of
      20 individuals with AD-FMD is clinically evaluated. This cohort consists of 15
      individuals with the recently described, recurrent mutation (c.1454C>T) in
      MAP3K7, as well as three individuals with missense mutations that result in
      substitutions in the N-terminal kinase domain of TGFbeta-activated kinase 1
      (TAK1), encoded by MAP3K7. Additionally, two individuals have missense variants
      in the gene TAB2, which encodes a protein with a close functional relationship to
      TAK1, TAK1-associated binding protein 2 (TAB2). Although the X-linked and
      autosomal dominant forms of FMD are very similar, there are distinctions to be
      made between the two conditions. Individuals with AD-FMD have characteristic
      facial features, and are more likely to be deaf, have scoliosis and cervical
      fusions, and have a cleft palate. Furthermore, there are features only found in
      AD-FMD in our review of the literature including valgus deformity of the feet and
      predisposition to keloid scarring. Finally, intellectual disability is present in
      a small number of subjects with AD-FMD but has not been described in association
      with X-linked FMD.

PMID- 28498506
TI  - A Novel Pregabalin Functionalized Salicylaldehyde Derivative Afforded Prospective
      Pain, Inflammation, and Pyrexia Alleviating Propensities.
AB  - A novel pregabalin derivative named as pregsal ((S,E)-3-(((2
      hydroxybenzylidene)amino)methyl)-5-methylhexanoic acid) was synthesized by a
      simple imination reaction between pregabalin and salicylaldehyde and was
      evaluated in the in vivo testing paradigms. The compound was characterized by UV,
      IR, 1 H, 13 C NMR, HR ESI-MS, and elemental analysis. It was screened (30, 50,
      75, and 100 mg/kg) for antinociceptive, anti-inflammatory, and antipyretic
      activities in relation to pregabalin. The synthesized compound significantly
      attenuated the tonic acetic acid-induced nociceptive pain (30 mg/kg (P < 0.05),
      50 mg/kg (P < 0.01), 75 and 100 mg/kg (P < 0.001)), and thermal-induced
      hyperalgesia (P < 0.001). These activities were succinctly antagonized (P < 0.05,
      P < 0.01, P < 0.001) by naloxone and pentylenetetrazole, implicating the
      involvement of opioidergic and GABAergic mechanisms. The compound also inhibited
      the temporal inflammatory response and alleviated the yeast-induced pyrexia (P <
      0.05, P < 0.01, and P < 0.001). These findings suggest that the synthesized
      compound possessed prospective pain, inflammation, and pyrexia relieving
      propensities and therefore may serve as a potential drug candidate for the
      therapeutic management of chronic pain conditions.

PMID- 28498507
TI  - Effect of surgical periodontal treatment associated to antimicrobial photodynamic
      therapy on chronic periodontitis: A randomized controlled clinical trial.
AB  - AIM: This randomized controlled clinical trial evaluated the effects of an
      adjunctive single application of antimicrobial photodynamic therapy (aPDT) in
      Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis
      (SCP). MATERIAL AND METHODS: In a split-mouth design, 20 patients with SCP were
      treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was
      applied in a single episode, using a diode laser and a phenothiazine
      photosensitizer. All patients were monitored until 90 days after surgical
      therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA
      hybridization at baseline, 60 and 150 days. Clinical and microbiological
      parameters were evaluated. RESULTS: In deep periodontal pockets depth (PPD >=5
      mm), Test Group presented a significantly higher decrease in PPD than Control
      Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated
      significantly less periodontal pathogens of red complex (Treponema denticola) (p
      < .05). CONCLUSION: A single episode of aPDT used in adjunct to open flap
      debridement of the root surface in the surgical treatment of SCP: i)
      significantly improved clinical periodontal parameters; ii) eliminates
      periodontal pathogens of the red complex more effectively (NCT02734784).

PMID- 28498508
TI  - Stroke in Women: Risk Factors and Clinical Biomarkers.
AB  - Stroke has been emerged as one of major health problems for women worldwide.
      Increasing of knowledge in this field has provided new data in this area which
      contribute to finding of new risk factors and could improve stroke treatment. A
      large number studies indicated a variety of risk factors including sex, age,
      race, smoking, diabetes, and physical inactivity could be involved in stroke in
      women. The understanding of various aspects involved in women stroke including
      risk factors, outcomes, stroke recovery, and prevention could provide new
      therapeutic platforms which could likely lead to better treatment in women
      stroke. Diagnosis is one of important steps in stroke therapy. It has been showed
      that a variety of biomarkers such as microRNAs (miRNAs), tPA, and von willebrand
      factor could be used as therapeutic and diagnostic biomarkers in stroke therapy.
      Here, we summarized various aspects of stroke in women which could help to
      recognition risk factors, outcomes, care, treatment, and novel biomarkers involve
      in treatment of stroke. J. Cell. Biochem. 118: 4191-4202, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28498509
TI  - Molecular interplays in hepatic stellate cells: apoptosis, senescence, and
      phenotype reversion as cellular connections that modulate liver fibrosis.
AB  - Liver fibrosis is a pathophysiological process correlated with intense repair and
      cicatrization mechanisms in injured liver, and over the past few years, the
      characterization of the fine-tuning of molecular interconnections that support
      the development of liver fibrosis has been investigated. In this cellular
      process, the hepatic stellate cells (HSCs) support the organ fibrogenesis. The
      HSCs are found in two distinct morpho-physiological states: quiescent and
      activated. In normal liver, most HSCs are found in quiescent state, presenting a
      considerable amount of lipid droplets in the cytoplasm, while in injured liver,
      the activated phenotype of HSCs is a myofibroblast, that secrete extracellular
      matrix elements and contribute to the establishment of the fibrotic process.
      Studies on the molecular mechanisms by which HSCs try to restore their quiescent
      state have been performed; however, no effective treatment to reverse fibrosis
      has been so far prescribed. Therefore, the elucidation of the cellular and
      molecular mechanisms of apoptosis, senescence, and the cell reversion phenotype
      process from activate to quiescent state will certainly contribute to the
      development of effective therapies to treat hepatic fibrosis. In this context,
      this review aimed to address central elements of apoptosis, senescence, and
      reversal of HSC phenotype in the control of hepatic fibrogenesis, as a guide to
      future development of therapeutic strategies.

PMID- 28498510
TI  - Semiautomated registration of pre- and intraoperative CT for image-guided
      percutaneous liver tumor ablation interventions.
AB  - PURPOSE: In CT-guided liver tumor ablation interventions, registration of a
      preoperative contrast-enhanced CT image to the intraoperative CT image is
      hypothesized to improve guidance. This is a highly challenging registration task
      due to differences in patient poses and large deformations, and therefore high
      registration errors are expected. In this study, our objective is to develop a
      method that enables users to locally improve the registration where the
      registration fails, with minimal user interaction. METHODS: The method is based
      on a conventional nonrigid intensity-based registration framework, extended with
      a novel point-to-surface penalty. The point-to-surface penalty serves to improve
      the alignment of the liver boundary, while requiring minimal user interaction
      during the intervention: annotating some points on the liver surface at those
      regions where the conventional registration seems inaccurate. RESULTS: The method
      is evaluated on 18 clinical datasets. It improves registration accuracy compared
      with the conventional nonrigid registration in terms of average surface distance
      (from 2.75 to 2.05 mm) and target registration error (from 6.92 to 5.8 mm).
      CONCLUSIONS: In this study, we introduce a semiautomated registration algorithm
      that improves the accuracy of image registration.

PMID- 28498511
TI  - Enhanced antitumor effect of targeted nanoliposomal bleomycin.
AB  - Folate receptor (FR)-mediated drug delivery is a promising approach for active
      targeting of drugs to the FR-positive tumor cells. Bleomycin (BLM) is an
      antitumor antibiotic with poor therapeutic activity as a result of its limited
      diffusion into tumor cells. The aim of this study was to investigate whether FR
      targeted PEGylated nanoliposomes (FPNL) can effectively deliver BLM to tumor
      cells and enhance its in vitro and in vivo efficacy. FPNL and PNL (non-targeted)
      were prepared by thin film hydration method, and their physiochemical properties,
      cellular uptake, tissue distribution and tumor inhibitory effects were
      investigated. In Lewis lung cancer (LLC1) cells, FPNL containing BLM showed 2.38
      fold and 3.26-fold higher cytotoxicity compared to PNL-BLM and free BLM,
      respectively. Moreover, the uptake of FPNL by these cells was increased as
      compared to the PNL. Furthermore, FPNL showed significantly higher tumor
      distribution of BLM in the LLC1 cells and more tumor inhibition efficacy compared
      to free BLM and PNL. Both formulations of nanoliposomes had longer plasma half
      life than that of free BLM. Therefore, FPNL may be suitable carriers for targeted
      drug delivery to FR-positive tumor cells.

PMID- 28498512
TI  - Recurrent ATP2A2 p.(Pro602Leu) mutation differentiates Acrokeratosis
      verruciformis of Hopf from the allelic condition Darier disease.
AB  - Darier disease and Acrokeratosis Verruciformis of Hopf (AKV) are rare disorders
      of keratinization with autosomal dominant inheritance and very distinct clinical
      pictures. Both have been shown to be caused by mutations in ATP2A2 (ATPase, Ca++
      transporting, cardiac muscle, slow-twitch) a gene encoding one of the SERCA
      (sarcoplasmic/endoplasmic reticulum calcium ATPase2) intracellular pumps with a
      crucial role in cell-to-cell adhesion in both skin and heart. While hundreds of
      different missense and nonsense mutations cause Darier disease, only one missense
      mutation, p.(Pro602Leu), has been identified in families with AKV. We report a
      family with AKV due to the p.(Pro602Leu) mutation and discuss implications for
      this recurrent mutation on knowledge of ATP2A2 structure and function.

PMID- 28498513
TI  - Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by
      inhibiting thioredoxin-related protein 14-mediated autophagy.
AB  - Paclitaxel is not as effective for neuroblastoma as most of the front-line
      chemotherapeutics due to drug resistance. This study explored the regulatory
      mechanism of paclitaxel-associated autophagy and potential solutions to
      paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was
      detected by scanning transmission electron microscopy and flow cytometry. The
      autophagy-associated proteins were assessed by western blot. Autophagy was
      induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and
      thioredoxin-related protein 14 (TRP14), were found to be upregulated in
      neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1
      or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In
      addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the
      TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel
      induced autophagy and enhanced the anticancer effects of paclitaxel in normal
      control cancer cells but not in cells with upregulated Beclin 1 and TRP14
      expression. Our findings showed that paclitaxel-induced autophagy in
      neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize
      neuroblastoma cells to paclitaxel by specifically inhibiting TRP14.

PMID- 28498514
TI  - Secukinumab re-initiation achieves regain of high response levels in patients who
      interrupt treatment for moderate to severe plaque psoriasis.

PMID- 28498515
TI  - Brain Structure Linking Delay Discounting and Academic Performance.
AB  - As a component of self-discipline, delay discounting refers to the ability to
      wait longer for preferred rewards and plays a pivotal role in shaping students'
      academic performance. However, the neural basis of the association between delay
      discounting and academic performance remains largely unknown. Here, we examined
      the neuroanatomical substrates underlying delay discounting and academic
      performance in 214 adolescents via voxel-based morphometry (VBM) by performing
      structural magnetic resonance imaging (S-MRI). Behaviorally, we confirmed the
      significant correlation between delay discounting and academic performance.
      Neurally, whole-brain regression analyses indicated that regional gray matter
      volume (rGMV) of the left dorsolateral prefrontal cortex (DLPFC) was associated
      with both delay discounting and academic performance. Furthermore, delay
      discounting partly accounted for the association between academic performance and
      brain structure. Differences in the rGMV of the left DLPFC related to academic
      performance explained over one-third of the impact of delay discounting on
      academic performance. Overall, these results provide the first evidence for the
      common neural basis linking delay discounting and academic performance. Hum Brain
      Mapp 38:3917-3926, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28498516
TI  - Nontopotactic Reaction in Highly Reversible Sodium Storage of Ultrathin Co9 Se8
      /rGO Hybrid Nanosheets.
AB  - Transition metal chalcogenide with tailored nanosheet architectures with reduced
      graphene oxide (rGO) for high performance electrochemical sodium ion batteries
      (SIBs) are presented. Via one-step oriented attachment growth, a facile synthesis
      of Co9 Se8 nanosheets anchored on rGO matrix nanocomposites is demonstrated. As
      effective anode materials of SIBs, Co9 Se8 /rGO nanocomposites can deliver a
      highly reversible capacity of 406 mA h g-1 at a current density of 50 mA g-1 with
      long cycle stability. It can also deliver a high specific capacity of 295 mA h g
      1 at a high current density of 5 A g-1 indicating its high rate capability.
      Furthermore, ex situ transmission electron microscopy observations provide
      insight into the reaction path of nontopotactic conversion in the hybrid anode,
      revealing the highly reversible conversion directly between the hybrid Co9 Se8
      /rGO and Co nanoparticles/Na2 Se matrix during the sodiation/desodiation process.
      In addition, it is experimentally demonstrated that rGO plays significant roles
      in both controllable growth and electrochemical conversion processes, which can
      not only modulate the morphology of the product but also tune the sodium storage
      performance. The investigation on hybrid Co9 Se8 /rGO nanosheets as SIBs anode
      may shed light on designing new metal chalcogenide materials for high energy
      storage system.

PMID- 28498517
TI  - Health utility reporting in chronic rhinosinusitis patients.
AB  - OBJECTIVES: Direct comparison of different diseases allows clinicians and
      researchers to place the burden of symptoms and impact on quality of life of each
      condition in context. Generic health-related quality-of-life assessment tools
      allow such analysis, and limited data are available for British patients with
      chronic rhinosinusitis. DESIGN: As part of a larger feasibility study, patients
      underwent baseline assessment using the SNOT-22, SF-12 and EQ-5D-5L tools. Data
      were analysed using Microsoft Excel and algorithms available for the analysis of
      the later two tools. We plotted EQ-5D-5L VAS and utility scores and SF-12 MCS and
      PCS scores separately against SNOT-22 scores and quantified associations using
      bivariate ordinary least squares regression analysis. SETTING: Patients were
      prospectively recruited from six UK outpatient clinics. PARTICIPANTS: Adult
      patients with chronic rhinosinusitis without nasal polyps (CRSsNPs). MAIN OUTCOME
      MEASURES: Baseline SNOT-22, SF-12 and EQ-5D-5L scores. RESULTS: Fifty-two adults
      were recruited with a mean age of 55 years, 51% were male. The mean SNOT-22 score
      was 43.82. Mental and physical component scores of the SF-12 were 46.53 and 46,
      respectively. Mean index score computed form the EQ-5D-5L was 0.75. Worse
      (higher) SNOT-22 scores were associated with lower EQ-5D-5L VAS and utility
      scores and SF-12 MCS and PCS scores. CONCLUSION: The EQ-5D-5L suggests that
      British CRSsNPs patients are negatively impacted with regards to quality of life.
      We found the SF-12 to be less sensitive and conclude that the EQ-5D-5L tool is a
      quick and accessible method for assessing QOL in order it can be compared with
      other disease states.

PMID- 28498518
TI  - Geophysical Investigation of Fresh-Saline Water Interface: A Case Study from
      South Punjab, Pakistan.
AB  - The importance of the study of fresh-saline water incursion cannot be over
      emphasized. Borehole techniques have been widely used, but they are quite
      expensive, intrusive, and time consuming. The electrical resistivity method has
      proved very successful in groundwater assessment. This advanced technique uses
      the calculation of Dar-Zarrouk (D-Z) parameters, namely longitudinal unit
      conductance, transverse unit resistance, and longitudinal resistivity has been
      employed by using 50 vertical electrical sounding points to assess the
      groundwater and delineate the fresh-saline water interface over 1045 km2 area of
      Khanewal in Southern Punjab of Pakistan. The x-y plots and maps of D-Z parameters
      were produced to establish a decipherable vision for the occurrence and
      distribution of different water-bearing formations of fresh-saline water aquifers
      through a complicated situation of intermixing of different resistivity ranges
      for fresh-saline water bodies. This technique is useful to reduce the ambiguity
      produced by the process of equivalence and suppression which cause intermixing in
      differentiating fresh, brackish, and saline aquifers during interpretation. The
      fresh-saline water interface is correlated very well with the previous studies of
      water quality analysis carried out in Khanewal area. The results suggest that the
      D-Z parameters are useful for demarcating different aquifer zones. The behavior
      and pattern of D-Z parameters with respect to occurrence and distribution of
      different water-bearing formations were effectively identified and delineated in
      the study area.

PMID- 28498519
TI  - Starting enteral nutrition with preterm single donor milk instead of formula
      affects time to full enteral feeding in very low birthweight infants.
AB  - AIM: This study compared the impact of using either single donor breastmilk or
      formula to start enteral feeding in preterm infants, on the time to full enteral
      feeding, growth and morbidity. The milk was provided by other preterm mothers.
      METHODS: This was an observational prospective study, carried out from June 2012
      to March 2013 at the Medical University of Vienna, Austria, on the effects of
      preterm single donor milk on 133 very low birthweight infants with a birthweight
      <1500 g and a gestational age <32 weeks until they were on full enteral feeding.
      They were compared to a retrospective group of 150 infants from March 2011 to May
      2012 who received preterm formula. RESULTS: The time to full enteral feeding,
      defined as 140 mL/kg, was significantly shorter in the donor milk group than in
      the formula group (18 vs. 22 days, p = 0.01). Feeding donor milk was also
      associated with a lower incidence for retinopathy of prematurity (4% vs. 13%, p <
      0.01) and culture-proven sepsis (11% vs. 23%, p < 0.01). CONCLUSION: Feeding
      preterm infants breastmilk from a single donor rather using formula was
      associated with a shorter time to full enteral feeding and lower incidences of
      retinopathy of prematurity and sepsis.

PMID- 28498520
TI  - Gold nanoparticles-conjugated quercetin induces apoptosis via inhibition of
      EGFR/PI3K/Akt-mediated pathway in breast cancer cell lines (MCF-7 and MDA-MB
      231).
AB  - Epidermal growth factor plays a major role in breast cancer cell proliferation,
      survival, and metastasis. Quercetin, a bioactive flavonoid, is shown to exhibit
      anticarcinogenic effects against various cancers including breast cancer. Hence,
      the present study was designed to evaluate the effects of gold nanoparticles
      conjugated quercetin (AuNPs-Qu-5) in MCF-7 and MDA-MB-231 breast cancer cell
      lines. Borohydride reduced AuNPs were synthesized and conjugated with quercetin
      to yield AuNPs-Qu-5. Both were thoroughly characterized by several
      physicochemical techniques, and their cytotoxic effects were assessed by MTT
      assay. Apoptotic studies such as DAPI, AO/EtBr dual staining, and annexin V-FITC
      staining were performed. AuNPs and AuNPs-Qu-5 were spherical with crystalline
      nature, and the size of particles range from 3.0 to 4.5 nm. AuNPs-Qu-5 exhibited
      lower IC50 value compared to free Qu. There was a considerable increase in
      apoptotic population with increased nuclear condensation seen upon treatment with
      AuNPs-Qu-5. To delineate the molecular mechanism behind its apoptotic role, we
      analysed the proteins involved in apoptosis and epidermal growth factor receptor
      (EGFR)-mediated PI3K/Akt/GSK-3beta signalling by immunoblotting and
      immunocytochemistry. The pro-apoptotic proteins (Bax, Caspase-3) were found to be
      up regulated and anti-apoptotic protein (Bcl-2) was down regulated on treatment
      with AuNPs-Qu-5. Additionally, AuNPs-Qu-5 treatment inhibited the EGFR and its
      downstream signalling molecules PI3K/Akt/mTOR/GSK-3beta. In conclusion,
      administration of AuNPs-Qu-5 in breast cancer cell lines curtails cell
      proliferation through induction of apoptosis and also suppresses EGFR signalling.
      AuNPs-Qu-5 is more potent than free quercetin in causing cancer cell death, and
      hence, this could be a potential drug delivery system in breast cancer therapy.

PMID- 28498521
TI  - Does drought stress modify the effects of plant-growth promoting rhizobacteria on
      an aboveground chewing herbivore?
AB  - Soil microbes have important effects on the interactions of plants with their
      environment, by promoting plant growth, inducing resistance to pests or by
      conferring tolerance to abiotic stress. However, their effects are variable and
      the factors responsible for this variation are mainly unknown. Our aim was to
      assess how drought stress modifies the effect of the nonpathogenic rhizobacterium
      Pseudomonas simiae WCS417r on plant growth and resistance against the generalist
      leaf-chewing caterpillar Mamestra brassicae. We studied Arabidopsis thaliana Col
      0 plants, as well as mutants altered in the biosynthesis of the phytohormones
      jasmonic acid (JA) and abscisic acid (ABA). Caterpillars did not prefer
      rhizobacteria-treated plants, independently of drought stress. Rhizobacteria
      colonization had a variable effect on caterpillar performance, which ranged from
      positive in one experiment to neutral in a second one. Drought had a consistent
      negative effect on herbivore performance; however, it did not modify the effect
      of rhizobacteria on herbivore performance. The effect of drought on herbivore
      performance was JA-mediated (confirmed with the use of the dde2-2 mutant), but it
      was still present in the ABA-deficient mutant aba2-1. Plant biomass was reduced
      by both drought and herbivory but it was enhanced by rhizobacterial colonization.
      Pseudomonas simiae WCS417r is able to promote plant growth even when plants are
      suffering herbivory. Nevertheless, the microbial effect on the herbivore is
      variable, independently of drought stress. To get the best possible outcome from
      the rhizobacteria-plant mutualism it is important to understand which other
      factors may be responsible for its context-dependency.

PMID- 28498522
TI  - Improving quality outcomes in head and neck free flap surgery with the use of a
      physician inpatient coordinator.
AB  - OBJECTIVES/HYPOTHESIS: Head and neck free flap patients require complex
      postoperative care. The quality of care for these patients often depends on their
      management from the time they leave the operating room. The purpose of this study
      was to investigate the impact of a postoperative inpatient coordinator (IC) for
      head and free flap patients on quality outcomes: length of stay (LOS), 30-day
      unplanned return to the emergency department (30dRED), 30-day unplanned
      readmissions (30dUR), and complication rates. STUDY DESIGN: Retrospective cohort
      study. METHODS: One hundred eighty-eight consecutive patients who underwent head
      and neck free flap surgery between January 2012 and January 2016 were reviewed
      using a prospective database. Patients had an IC for their entire hospitalization
      (group 1) or for less than their entire hospitalization (group 2). Logistic
      regression analysis was performed to identify risk factors for quality outcomes.
      RESULTS: Mean LOS was 13.8 days and 17.3 days in groups 1 and 2, respectively (P
      = .002). The 30dRED rate was 12% and 22%, respectively (P = .04). Group 2 had an
      increased LOS by 4.1 days (P = .001) and a 2.4 fold increased 30dRED (P = .03).
      30dUR and complications were not influenced by the IC (P > .05). CONCLUSIONS: An
      IC may help decrease LOS and 30dRED in head and neck free flap patients. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:336-342, 2018.

PMID- 28498523
TI  - Effects of chemical management for invasive plants on the performance of
      Lithobates pipiens tadpoles.
AB  - Invasive plants impact amphibians by altering habitat, altering species
      interactions, and releasing potentially toxic secondary chemicals. Despite being
      costly and having the potential to affect nontarget wildlife, chemical management
      is commonly used to control invasive plants. Prior research has indicated that
      individual effects of invasive plants or herbicides can be harmful to aquatic
      organisms; however, information is lacking on the combined effect of these
      factors on amphibians. A laboratory experiment was performed to assess the impact
      of leachates of the invasive plants Eurasian watermilfoil (Myriophyllum spicatum)
      and European buckthorn (Rhamnus cathartica), the herbicide Renovate(r) 3
      (triclopyr [3, 5, 6-trichloro-2-pyridinyloxyacetic acid]), and the combined
      effects of each plant leachate and the herbicide on the growth, morphology, and
      survival of northern leopard frog (Lithobates pipiens) tadpoles. No effects of
      treatment on survival were observed. Tadpole exposure to M. spicatum reduced body
      mass by 17%, exposure to R. cathartica increased body mass by 36%, and exposure
      to R. cathartica + low herbicide increased body mass by 38% (although only early
      in the experiment). Exposure to Renovate 3 induced a 16% and 29% decrease in
      tadpole size in lower (0.22 mg triclopyr active ingredient [a.i.]/L) and higher
      (0.92 mg triclopyr a.i./L) concentration treatments, respectively. Results from
      the present study highlight the importance of considering both individual and
      combined effects of invasive plants and herbicides because they may have
      different outcomes for tadpole growth and development. Environ Toxicol Chem
      2017;36:2958-2964. (c) 2017 SETAC.

PMID- 28498524
TI  - Patterns of chronic hand eczema: a semantic map analysis of the CARPE registry
      data.
AB  - BACKGROUND: Hand eczema has a high incidence and prevalence and has a negative
      impact on both physical and psychological well-being, with the risk of
      persistence as a chronic condition. Epidemiological studies on hand eczema
      provided mainly descriptive and risk analyses, but pattern analyses of variables
      associated with hand eczema, in particular chronic hand eczema, have not been
      explored to date. OBJECTIVES: To investigate and display the semantics of
      associations between variables of hand eczema obtained from the Swiss and German
      registries of chronic hand eczema (CARPE) to dissect patterns and novel links.
      METHODS: This was a cross-sectional study on selected variables from the CARPE
      registries. Associations between variables were analysed by means of an
      autoassociative system. A semantic connectivity map was generated by using a
      maximum spanning tree algorithm. RESULTS: Baseline datasets of 1466 patients with
      chronic hand eczema (Switzerland: 199; Germany: 1267) were analysed. Occupational
      exposure had the highest impact in the total and country cohorts. We identified
      two areas of exposure linked to corresponding occupations that clearly demarcated
      the sexes. CONCLUSIONS: This study, using semantic connectivity as a novel method
      of data analysis, reveals the complexity of features characterizing chronic hand
      eczema as well as novel association patterns that deserve further investigation.

PMID- 28498526
TI  - The Role of Mothers' Communication in Promoting Motivation for Math and Science
      Course-Taking in High School.
AB  - In the context of concerns about American youths' failure to take advanced math
      and science (MS) courses in high school, we examined mothers' communication with
      their adolescent about taking MS courses. At ninth grade, U.S. mothers (n = 130)
      were interviewed about their responses to hypothetical questions from their
      adolescent about the usefulness of algebra, geometry, calculus, biology,
      chemistry, and physics. Responses were coded for elaboration and making personal
      connections to the adolescent. The number of science, technology, engineering,
      and mathematics courses taken in 12th grade was obtained from school records.
      Mothers' use of personal connections predicted adolescents' MS interest and
      utility value, as well as actual MS course-taking. Parents can play an important
      role in motivating their adolescent to take MS courses.

PMID- 28498527
TI  - Adolescent Conflict Appraisals Moderate the Link Between Marital Conflict and
      Physiological Stress Reactivity.
AB  - The goal of this study was to advance understanding of how adolescent conflict
      appraisals contribute uniquely, and in combination with interparental conflict
      behavior, to individual differences in adolescent physiological reactivity.
      Saliva samples were collected from 153 adolescents (52% female; ages 10-17 years)
      before and after the Trier Social Stress Test. Saliva was assayed for cortisol
      and alpha-amylase. Results revealed interactive effects between marital conflict
      and conflict appraisals. For youth who appraised parental conflict negatively
      (particularly as threatening), negative marital conflict predicted dampened
      reactivity; for youth who appraised parental conflict less negatively, negative
      marital conflict predicted heightened reactivity. These findings support the
      notion that the family context and youth appraisals of family relationships are
      linked with individual differences in biological sensitivity to context.

PMID- 28498525
TI  - The Shared Etiology of Attentional Control and Anxiety: An Adolescent Twin Study.
AB  - We investigated the etiology of attentional control (AC) and four different
      anxiety symptom types (generalized, obsessive-compulsive, separation, and social)
      in an adolescent sample of over 400 twin pairs. Genetic factors contributed to
      55% of the variance in AC and between 43 and 58% of the variance in anxiety.
      Negative phenotypic associations between AC and anxiety indicated that lower
      attentional ability is related to increased risk for all 4 anxiety categories.
      Genetic correlations between AC and anxiety phenotypes ranged from -.36 to -.47,
      with evidence of nonshared environmental covariance between AC and generalized
      and separation anxiety. Results suggest that AC is a phenotypic and genetic risk
      factor for anxiety in early adolescence, with somewhat differing levels of risk
      depending on symptomatology.

PMID- 28498528
TI  - Family, Peer, and Pubertal Determinants of Dating Involvement Among Adolescents.
AB  - This study examines the influence of family, peer, and biological contributors to
      dating involvement among early adolescents (11-14 years of age; n = 244).
      Further, we assess how parental monitoring may be modified by pubertal maturation
      and older sibling risky behavior. Data on delinquent peer affiliation, pubertal
      maturation, parental monitoring, older sibling risky behavior, and dating
      involvement were gathered through observations and surveys from adolescents,
      mothers, older siblings, and teachers. Results indicate that lower levels of
      parental monitoring and higher levels of older sibling risky behavior were
      related to adolescents' dating involvement through delinquent peer affiliation.
      Pubertal maturation was directly related to dating involvement for early daters.
      Findings emphasize the value of examining social and biological factors, in
      concert, over time.

PMID- 28498529
TI  - Mother-Adolescent Proficiency in a Common Language Facilitates Socialization
      Among Mexican-Origin Families.
AB  - The primary goal of this study was to test how mother and adolescent proficiency
      in a common language moderates the link from parenting to adolescent development.
      A sample of Mexican-origin fifth-grade adolescents (N = 674, 50% female) was
      measured longitudinally on self-control and aggression. Mothers were rated on
      observed positive discipline, warmth, and harsh discipline. Positive discipline
      and warm parenting predicted increases in self-control and decreases in
      aggression, but only among mother-adolescent dyads who were proficient in a
      common language. Harsh parenting predicted decreases in self-control and
      increases in aggression, but only among dyads who were not proficient in a common
      language. Similar results were found in a conceptual replication among a second
      sample of 167 Mexican-origin adolescents.

PMID- 28498530
TI  - Examining Discrimination, Ethnic-Racial Identity Status, and Youth Public Regard
      Among Black, Latino, and White Adolescents.
AB  - How positively adolescents believe others feel about their ethnic-racial group
      (i.e., public regard) is an important part of their ethnic-racial identity (ERI),
      which is likely informed by contextual and individual factors. Using cluster
      analyses to generate ERI statuses among Black, Latino, and White adolescents (n =
      1,378), we found that associations between peer versus adult discrimination and
      public regard varied across ERI status and ethnic-racial group. However, among
      all adolescents, an achieved ERI (i.e., having explored ethnicity-race and having
      a clear sense about its personal meaning) buffered the negative association
      between adult discrimination and public regard, but not between peer
      discrimination and public regard. Implications for understanding the interplay
      between contextual and individual factors for public regard are discussed.

PMID- 28498532
TI  - The Impact of Adolescents' Classroom and Neighborhood Ethnic Diversity on Same-
      and Cross-Ethnic Friendships Within Classrooms.
AB  - This study examines how classroom and neighborhood ethnic diversity affect
      adolescents' tendency to form same- versus cross-ethnic friendships when they
      enter middle school. Hypotheses are derived from exposure, conflict, and
      constrict theory. Hypotheses are tested among 911 middle school students (43
      classrooms, nine schools) in the Netherlands. Multilevel (p2) social network
      analyses show that students were more likely to engage in same-ethnic rather than
      cross-ethnic friendships. In line with conflict theory, greater classroom and
      neighborhood diversity were related to stronger tendencies to choose same-ethnic
      rather than cross-ethnic friends, among both ethnic majority and minority
      students. Diversity did not hamper reciprocity, as students in more ethnically
      diverse classrooms were even more likely to reciprocate friendships.

PMID- 28498531
TI  - Developmental Latent Patterns of Identification as Mostly Heterosexual Versus
      Lesbian, Gay, or Bisexual.
AB  - Scant research exists on the development of mostly heterosexual identity, the
      largest sexual orientation minority subgroup. We used longitudinal latent class
      analysis to characterize the patterns of identification with lesbian, gay,
      bisexual (LGB), or mostly heterosexual identities from ages 12 to 23 in 13,859
      youth (57% female) in a U.S. national cohort. Three classes emerged: completely
      heterosexual (88.2%), mostly heterosexual (9.5%), and LGB (2.4%). LGB class youth
      generally identified with sexual minority identities by ages 12-17. In contrast,
      mostly heterosexual class youth identified with sexual minority identities
      gradually, with steady increases in endorsement starting at the age of 14.
      Developmental implications of these differential patterns are discussed.

PMID- 28498533
TI  - Modeling Trajectories of Adolescent-Perceived Family Conflict: Effects of Marital
      Dissatisfaction and Parental Alcoholism.
AB  - We evaluated the effects of marital dissatisfaction on adolescent-perceived
      conflict in 435 families with and without a parental history of alcoholism. On
      average, family conflict decreased linearly as adolescents aged. Families with an
      alcoholic parent demonstrated higher adolescent-reported family conflict and this
      effect was partially mediated by higher mother- and father-reported marital
      dissatisfaction. Families with higher marital dissatisfaction had greater
      conflict when adolescents were young (based on fathers' marital dissatisfaction)
      and as they aged (based on mother's marital dissatisfaction). Years in which
      mothers reported higher marital dissatisfaction than usual coincided with years
      in which adolescents reported greater family conflict. Results indicate that
      marital dissatisfaction has both within and between-family effects on adolescent
      perceptions of conflict.

PMID- 28498534
TI  - Adolescent Life Stress and the Cortisol Awakening Response: The Moderating Roles
      of Attachment and Sex.
AB  - This longitudinal study investigated how past versus current life stresses relate
      to adolescents' cortisol awakening response (CAR), an index of hypothalamic
      pituitary-adrenal activity. Ninety-nine adolescents reported previous year life
      stress at ages 12 and 18. At the second assessment, participants also provided
      self-reports of parent and peer attachment and 3 days of cortisol samples.
      Current stress was associated with heightened CAR for both males and females,
      whereas past stress was associated with attenuated CAR for males. Attachment to
      peers buffered the relationship between past stress and attenuated CAR for all
      adolescents; attachment to parents was a buffer for male adolescents only.
      Results demonstrate the protective roles of adolescent relationships and
      highlight sex differences in biopsychosocial development across adolescence.

PMID- 28498535
TI  - Domain Specificity in Adolescents' Concepts of Laws: Associations Among Beliefs
      and Behavior.
AB  - Using detailed vignettes and scale measures, concepts of laws regulating domain
      specific issues and engagement in delinquency were assessed among 340 9th through
      12th graders (Mage = 16.64, SD = 1.37). Adolescents distinguished between laws
      that regulate moral, drug-related prudential, conventional, personal, and
      multifaceted issues in their criterion judgments and justifications. Youths'
      ratings of the importance of laws, obligation to obey laws, and deserved
      punishment for breaking different laws also followed domain-consistent patterns.
      Adolescents' engagement in moral, drug-related prudential, and multifaceted forms
      of delinquency was associated with less supportive judgments about laws within
      the same domain. Findings contribute to civic development research by
      demonstrating domain specificity in adolescents' beliefs about laws and suggest
      that these beliefs are linked with engagement in similar types of delinquency.

PMID- 28498536
TI  - Unauthorized Status and Youth Development in the United States: Consensus
      Statement of the Society for Research on Adolescence.
AB  - In the United States, 5.3 million children and adolescents are growing up either
      with unauthorized status or with at least one parent who has that status. Until
      recently, little in the way of research has informed federal, state, and local
      policy debates related to unauthorized status (e.g., border enforcement,
      deportation, and a pathway to citizenship) although these issues have important
      implications for youth development. This statement is a brief summary of the
      research evidence on multiple domains of development that may be affected by the
      child or parent's unauthorized status. We also describe the contextual and
      psychological mechanisms that may link this status to developmental outcomes. We
      summarize a range of policies and practices that could reduce the developmental
      harm to children, youth, and their families stemming from this status. Finally,
      we conclude with recommendations for policy, practice, and research that are
      based on the evidence reviewed.

PMID- 28498537
TI  - Contagion of Anxiety Symptoms Among Adolescent Siblings: A Twin Study.
AB  - This study examined whether social contagion of anxiety symptoms is present
      between siblings during early adolescence and whether this process is moderated
      by sex, relationship quality, and zygosity. Based on 634 monozygotic and
      dizygotic twins (336 females) assessed in Grades 6 and 7, anxiety symptoms and
      sibling relationship quality were measured with self-report questionnaires. The
      predictive association of the co-twin's level of anxiety with adolescents' own
      increased anxiety 1 year later was only observed in same-sex twin dyads
      (monozygotic and dizygotic) and was higher for those who perceived a higher level
      of relationship quality with their co-twin. Raising awareness of a possible
      sibling contagion of anxiety may be useful for preventing the development of
      anxiety symptoms in youth.

PMID- 28498538
TI  - Hanging Out With the Right Crowd: Peer Influence on Risk-Taking Behavior in
      Adolescence.
AB  - Peer influence plays a key role in the increase of risk-taking behavior during
      adolescence. However, its underlying processes are not fully understood. This
      study examined the effects of social norms, conveyed through peer advice, on risk
      taking behavior in 15- to 17-year-old adolescents (N = 76). Participants played a
      card-guessing task alone and with online peer advice. Results showed that risk
      taking increased in the presence of peers. The results further showed that
      adolescents took into account the uncertainty associated with gambles, as well as
      the social norms conveyed by peers. Our findings suggest that peers are most
      influential in uncertain situations and demonstrate the value of a social norms
      approach in examining the processes underlying peer effects.

PMID- 28498539
TI  - Part-Time Employment and Problem Behaviors: Evidence From Adolescents in South
      Korea.
AB  - This study explores the impact of adolescent part-time work experience on problem
      behaviors in the South Korean context. To achieve this, propensity score matching
      (PSM) analyses were employed based on data from the Korean Education Employment
      Panel (KEEP). Results indicate that adolescents' part-time employment during
      their secondary school years had significantly undesirable effects on drinking
      and smoking, even after preexisting differences between the two groups (i.e.,
      those adolescents who participated in part-time work and those who did not) were
      controlled by PSM. However, an insignificant difference was detected in the
      likelihood of running away from home. Implications of the results are discussed
      in terms of changes in the meanings of adolescence and of participating in part
      time work in South Korea.

PMID- 28498540
TI  - Patterns of Adolescent Regulatory Responses During Family Conflict and Mental
      Health Trajectories.
AB  - Four distinct patterns of adolescents' behavioral, emotional, and physiological
      responses to family conflict were identified during mother-father-adolescent (M =
      13.08 years) interactions. Most youth displayed adaptively regulated patterns
      comprised of low overt and subjective distress. Under-controlled adolescents
      exhibited elevated observable and subjective anger. Over-controlled adolescents
      were withdrawn and reported heightened subjective distress. Physiologically
      reactive adolescents had elevated cortisol coupled with low overt and subjective
      distress. Regulation patterns were associated with unique mental health
      trajectories. Under-controlled adolescents had elevated conduct and peer problems
      whereas over-controlled adolescents had higher anxiety and depressive symptoms.
      Physiologically reactive adolescents had low concurrent, but increasing levels of
      depressive, anxiety, and peer problem symptoms. Findings underscore the
      importance of examining organizations of regulatory strategies in contributing to
      adolescent mental health.

PMID- 28498541
TI  - Current data about the benefit of prehabilitation for colorectal cancer patients
      undergoing surgery are not sufficient to alter the NHS cancer waiting targets.

PMID- 28498542
TI  - Cloud Watching in Clinical Pathology.

PMID- 28498543
TI  - Infliximab biosimilar CT-P13 in the treatment of chronic plaque psoriasis: data
      from the Psobiosimilars registry.

PMID- 28498544
TI  - Metabolic engineering of cofactor flavin adenine dinucleotide (FAD) synthesis and
      regeneration in Escherichia coli for production of alpha-keto acids.
AB  - Cofactor flavin adenine dinucleotide (FAD) plays a vital role in many FAD
      dependent enzymatic reactions; therefore, how to efficiently accelerate FAD
      synthesis and regeneration is an important topic in biocatalysis and metabolic
      engineering. In this study, a system involving the synthesis pathway and
      regeneration of FAD was engineered in Escherichia coli to improve alpha-keto acid
      production-from the corresponding l-amino acids-catalyzed by FAD-dependent l
      amino acid deaminase (l-AAD). First, key genes, ribH, ribC, and ribF, were
      overexpressed and fine-tuned for FAD synthesis. In the resulting E. coli strain
      PHCF7, strong overexpression of pma, ribC, and ribF and moderate overexpression
      of ribH yielded a 90% increase in phenylpyruvic acid (PPA) titer: 19.4 +/- 1.1 g
      . L-1 . Next, formate dehydrogenase (FDH) and NADH oxidase (NOX) were
      overexpressed to strengthen the regeneration rate of cofactors FADH2 /FAD using
      FDH for FADH2 /FAD regeneration and NOX for NAD+ /NADH regeneration. The
      resulting E. coli strain PHCF7-FDH-NOX yielded the highest PPA production: 31.4
      +/- 1.1 g . L-1 . Finally, this whole-cell system was adapted to production of
      other alpha-keto acids including alpha-ketoglutaric acid, alpha-ketoisocaproate,
      and keto-gamma-methylthiobutyric acid to demonstrate the broad utility of
      strengthening of FAD synthesis and FADH2 /FAD regeneration for production of
      alpha-keto acids. Notably, the strategy reported herein may be generally
      applicable to other flavin-dependent biocatalysis reactions and metabolic pathway
      optimizations. Biotechnol. Bioeng. 2017;114: 1928-1936. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28498545
TI  - Fluorogenic Sensing of Carcinogenic Bisphenol A using Aptamer-Capped Mesoporous
      Silica Nanoparticles.
AB  - Mesoporous silica nanoparticles loaded with rhodamine B and capped with a
      bisphenol A aptamer were used for the selective and sensitive detection of this
      lethal chemical. The pores of the nanoparticles are selectively opened in the
      presence of bisphenol A (through its selective coordination with the aptamer)
      with subsequent rhodamine B delivery. With this capped material a limit of
      detection as low as 3.5 MUm of bisphenol A was measured.

PMID- 28498546
TI  - The use of inverted-L posteromedial thigh (L-PMT) flap for autologous breast
      reconstruction: A case report.
AB  - The posteromedial thigh (PMT) flap has been described for breast reconstruction
      in vertical fashion (vPMT). However, it might not incorporate enough soft tissue
      for reconstruction of a medium size breast. Here, we present a case utilizing the
      free inverted-L posteromedial thigh (L-PMT) flap for autologous reconstruction of
      the breast. A 65-year-old woman with a body max index (BMI) of 24.5 kg/m2
      underwent nipple sparring mastectomy and received immediate unilateral breast
      reconstruction. The flap was raised based on the first medial perforator of the
      profunda femoris artery (PFA). The internal mammary artery and vein were
      dissected as recipient vessels. The flap size was 25 cm * 25 cm. The mastectomy
      specimen and weight of the flap was 260 g and 310 g, respectively. The flap
      survived completely after surgery. The donor site was primarily closed with
      minimal morbidities. Follow-up observations were conducted from 1 to 6 months.
      The patient was satisfied with the reconstruction. The free L-PMT flap may be
      suitable for breast reconstruction in women with moderate breast size. The
      inverted-L pattern of the PMT flap allows the surgeon to include a bigger
      quantity of flap soft tissue enabling a more anatomical shape of the breast and
      represents an alternative design that may be used for autologous breast
      reconstruction in selected patients.

PMID- 28498547
TI  - The narcotic clinic in New Orleans, 1919-21.
AB  - AIMS: This paper traces the history of the narcotic clinic in New Orleans,
      Louisiana, comparing its merits to a similar clinic in Shreveport. How do the
      clinics compare, and why did the Shreveport clinic operate for longer than its
      New Orleans counterpart? METHODS: Qualitative analysis of contemporary medical
      journals and newspapers, as well as archival materials from the Narcotic
      Division. In addition, the records of Louisiana Governor John M. Parker, the
      papers of Dr Willis P. Butler in Shreveport, as well as the records of the
      Orleans Parish Medical Society have been utilized. FINDINGS: The narcotic clinic
      in Shreveport benefited from strong local support, while the New Orleans clinic
      faced a more vocal opposition. In addition, the Shreveport clinic offered a broad
      array of services and was a pillar of the community; the New Orleans clinic was
      newly established and offered fewer services. It was especially the influx of out
      of-state addicts that angered many New Orleanians, many of whom witnessed the
      addicts lined up in the French Quarter. CONCLUSION: The effectiveness of the
      narcotic clinics in Louisiana (1919-23) was influenced by local opinion. The New
      Orleans clinic faced a tougher political climate than its counterpart in
      Shreveport, and therefore proved less resilient in the face of federal
      opposition.

PMID- 28498550
TI  - HBx protein-mediated ATOH1 downregulation suppresses ARID2 expression and
      promotes hepatocellular carcinoma.
AB  - Hepatitis B virus X protein plays a crucial role in the pathogenesis of
      hepatocellular carcinoma. We previously showed that the tumor suppressor ARID2
      inhibits hepatoma cell cycle progression and tumor growth. Here, we evaluated
      whether hepatitis B virus X protein was involved in the modulation of ARID2
      expression and hepatocarcinogenesis associated with hepatitis B virus infection.
      ARID2 expression was downregulated in HBV-replicative hepatoma cells, HBV
      transgenic mice, and HBV-related clinical HCC tissues. The expression levels of
      HBx were negatively associated with those of ARID2 in hepatocellular carcinoma
      tissues. Furthermore, HBx suppressed ARID2 at transcriptional level.
      Mechanistically, the promoter region of ARID2 gene inhibited by HBx was located
      at nt-1040/nt-601 and contained potential ATOH1 binding elements. In addition,
      ectopic expression of ATOH1 or mutation of ATOH1 binding sites within ARID2
      promoter partially abolished HBx-triggered ARID2 transcriptional repression.
      Functionally, ARID2 abrogated HBx-enhanced migration and proliferation of
      hepatoma cells, whereas depletion of ATOH1 enhanced tumorigenecity of HCC cells.
      Therefore, our findings suggested that deregulation of ARID2 by HBx through ATOH1
      may be involved in HBV-related hepatocellular carcinoma development.

PMID- 28498548
TI  - Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling.
AB  - Activation of cardiac fibroblasts into myofibroblasts is considered to play an
      essential role in cardiac remodeling and fibrosis. A limiting factor in studying
      this process is the spontaneous activation of cardiac fibroblasts when cultured
      on two-dimensional (2D) culture plates. In this study, a simplified three
      dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by
      transforming growth factor-beta1 (TGF-beta1), is presented to recapitulate a
      fibrogenic microenvironment. It is hypothesized that the quiescent state of
      cardiac fibroblasts can be maintained by mimicking the mechanical stiffness of
      native heart tissue. To test this hypothesis, a 3D cell culture model consisting
      of cardiomyocytes and cardiac fibroblasts encapsulated within a mechanically
      engineered gelatin methacryloyl hydrogel, is developed. The study shows that
      cardiac fibroblasts maintain their quiescent phenotype in mechanically tuned
      hydrogels. Additionally, treatment with a beta-adrenergic agonist increases
      beating frequency, demonstrating physiologic-like behavior of the heart
      constructs. Subsequently, quiescent cardiac fibroblasts within the constructs are
      activated by the exogenous addition of TGF-beta1. The expression of fibrotic
      protein markers (and the functional changes in mechanical stiffness) in the
      fibrotic-like tissues are analyzed to validate the model. Overall, this 3D
      engineered culture model of contractile cardiac tissue enables controlled
      activation of cardiac fibroblasts, demonstrating the usability of this platform
      to study fibrotic remodeling.

PMID- 28498551
TI  - Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients
      previously treated with a direct-acting antiviral regimen.
AB  - : The optimal retreatment strategy for patients chronically infected with
      hepatitis C virus who experience virologic failure after treatment with direct
      acting antiviral-based therapies remains unclear. In this multicenter, open
      label, phase 2 study, we evaluated the efficacy and safety of a fixed-dose
      combination of sofosbuvir-velpatasvir (400 mg/100 mg) plus weight-adjusted
      ribavirin administered for 24 weeks in patients who did not achieve sustained
      virologic response after prior treatment with direct-acting antiviral regimens
      that included the nucleotide analogue nonstructural protein 5B inhibitor
      sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or
      without the nonstructural protein 3/4A protease inhibitor voxilaprevir. The
      primary efficacy endpoint was the proportion of patients achieving sustained
      virologic response at 12 weeks after the cessation of treatment. In total, 63 of
      69 (91%; 95% confidence interval, 82%-97%) patients achieved sustained virologic
      response at 12 weeks, including 36 of 37 (97%; 95% confidence interval, 86%-100%)
      patients with hepatitis C virus genotype 1 infection, 13 of 14 (93%; 95%
      confidence interval, 66%-100%) patients with genotype 2 infection, and 14 of 18
      (78%; 95% confidence interval, 52%-94%) patients with genotype 3 infection. Most
      adverse events were of mild or moderate severity. The most frequently reported
      adverse events were fatigue, nausea, headache, insomnia, and rash. One patient
      (1%) with genotype 1a infection discontinued all study drugs due to an adverse
      event (irritability). CONCLUSION: Retreatment of patients who previously failed
      direct-acting antiviral-based therapies with sofosbuvir-velpatasvir plus
      ribavirin for 24 weeks was well tolerated and effective, particularly those with
      hepatitis C virus genotype 1 or 2 infection. (Hepatology 2017;66:1083-1089).

PMID- 28498552
TI  - Ex vivo biomechanical stability of 5 cricoid-suture constructs for equine
      laryngoplasty.
AB  - OBJECTIVE: To determine the biomechanical properties of 5 suture constructs in
      the equine cricoid under cyclic loading and load to failure testing. STUDY
      DESIGN: Ex vivo study. SAMPLES: Seventy-five equine cadaver larynges. METHODS:
      Each larynx was implanted with 1 of 5 cricoid-suture constructs. The standard
      laryngoplasty, where a suture is passed once through the cricoid, including its
      caudal edge, was used in 2 constructs: 1 with 5 USP Ethibond (ES) and 1 with 2 mm
      Fibertape (FS). In the third construct, the 2 mm Fibertape was passed twice
      through the cricoid including its caudal edge (Double Loop-DL). Constructs 4 and
      5 used 2 mm Fibertape in a U-shaped loop passed through the cricoid but excluding
      its caudal edge. One construct was supported with a metallic button (MB) on the
      caudo-ventral aspect of the cricoid while the other included only the U-shaped
      loop (U). Constructs were subjected to cyclic loading and to single cycle to
      failure. Reduction of the left-to-right arytenoid angle quotient (LRQ), suture
      migration, and load at failure were compared. RESULTS: LRQ reduction after cyclic
      loading was lower in MB and U than ES constructs. During cyclic loading, suture
      migration was reduced in MB, U, and DL compared to ES constructs. Mean load at
      failure was lower in FS and U than in ES constructs. CONCLUSION: Loss of
      abduction after equine laryngoplasty may be reduced and pullout forces increased
      by applying a MB construct in the cricoid cartilage. In vivo testing is required
      to verify these results.

PMID- 28498553
TI  - Fundamentals of Clinical Pharmacology With Application for Pregnant Women.
AB  - Medication use is common in pregnancy, yet for most medications the optimal
      formulation and dosage have not been described specifically for pregnant women.
      Often, adverse effects are only discovered anecdotally or after extensive off
      label use occurs. Since pharmacologic research that includes pregnant women is
      sparse and animal studies are often not applicable to the human fetus, providers
      must use knowledge of drug behavior and normal physiologic changes of pregnancy
      to personalize treatment for pregnant women. In this review, we present an
      overview of the basic concepts of clinical pharmacology: pharmacokinetics,
      pharmacodynamics, and pharmacogenomics. The normal physiologic changes of
      pregnancy are presented as a framework to understand alterations in drug
      behavior. A clinical vignette that addresses 4 pregnancy scenarios involving
      medications-preterm birth, vaccination, herpes simplex virus infection, and
      codeine toxicity-is provided to illustrate application of core clinical
      pharmacologic concepts. Discussion of relevant literature illustrates the
      challenges of offering individualized pharmacologic therapy in pregnancy.

PMID- 28498554
TI  - Differential resistance to platinum-based drugs and 5-fluorouracil in p22phox
      overexpressing oral squamous cell carcinoma: Implications of alternative
      treatment strategies.
AB  - BACKGROUND: We have previously shown that p22phox confers resistance to cisplatin
      in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation
      with cisplatin resistance and affects the efficacy of other platinum or
      nonplatinum drugs is unknown. METHODS: The p22phox expression in tissues and
      apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity
      of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo
      chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft
      mouse model. RESULTS: The p22phox was upregulated in tumors of patients with OSCC
      refractory to cisplatin treatment. The p22phox overexpression markedly increased
      the resistance to cisplatin and carboplatin, but not oxaliplatin and 5
      fluorouracil (5-FU), in OSCC cells by differentially inhibiting the drug-induced
      apoptosis. Furthermore, p22phox-dependent resistance to cisplatin, but not 5-FU,
      was demonstrated in mouse xenograft tumors. CONCLUSION: The p22phox expression
      may not only be a prognostic biomarker for prediction of chemotherapy outcomes,
      but the indication for alternative treatment strategies in oral cancer.

PMID- 28498555
TI  - Trauma-Related Pain, Reexperiencing Symptoms, and Treatment of Posttraumatic
      Stress Disorder: A Longitudinal Study of Veterans.
AB  - Research has demonstrated a strong positive association between posttraumatic
      stress disorder (PTSD) symptoms and physical pain. However, few studies have
      explored the impact of pain problems on the symptoms and treatment of PTSD, and
      results remain inconsistent. This longitudinal study examined whether trauma
      related and trauma-unrelated pain differentially and uniquely predicted
      reexperiencing symptoms. We also examined whether levels of reexperiencing
      symptoms mediated the relationship between pain intensity and posttreatment
      symptoms of avoidance, numbing, and hyperarousal (ANH). Analyses were conducted
      using archival data from 99 treatment-seeking veterans who reported the etiology
      and intensity of their pain and severity of PTSD symptoms pre- and posttreatment.
      Among veterans with trauma-related pain, pain intensity (a) uniquely corresponded
      to greater posttreatment reexperiencing symptoms (b = 1.09), and (b) was
      indirectly predictive of ANH symptoms via the reexperiencing symptoms (b = 1.93).
      However, veterans with trauma-unrelated pain evidenced no associations between
      pain intensity and reexperiencing (b = 0.04) or ANH symptoms (b = 0.06). We thus
      found that trauma-related pain was indirectly related to poor PTSD treatment
      outcomes via reexperiencing symptoms. These findings offer additional insight
      into factors that may influence PTSD treatment outcomes for pain-suffering trauma
      survivors.

PMID- 28498556
TI  - Adaptive and maladaptive functioning in Kleefstra syndrome compared to other rare
      genetic disorders with intellectual disabilities.
AB  - Detailed neurobehavioural profiles are of major value for specific clinical
      management, but have remained underexposed in the population with intellectual
      disabilities (ID). This was traditionally classified based on IQ level only.
      Rapid advances in genetics enable etiology based stratification in the majority
      of patients, which reduces clinical heterogeneity. This paper illustrates that
      specific profiles can be obtained for rare syndromes with ID. Our main aim was to
      study (mal)adaptive functioning in Kleefstra Syndrome (KS) by comparing and
      contrasting our findings to three other subgroups: Koolen-de Vries Syndrome,
      GATAD2B-related syndrome, and a mixed control group of individuals with ID. In
      total, we studied 58 individuals (28 males, 30 females) with ID; 24 were
      diagnosed with KS, 13 with Koolen-de Vries Syndrome, 6 with the GATAD2B-related
      syndrome, and 15 individuals with undefined neurodevelopmental disorders. All
      individuals were examined with a Vineland Adaptive Behavior Scale, mini PAS-ADD
      interview, and an Autism Diagnostic Observation Schedule to obtain measures of
      adaptive and maladaptive functioning. Each of the three distinctive genetic
      disorders showed its own specific profile of adaptive and maladaptive
      functioning, while being contrasted mutually. However, when data of the subgroups
      altogether are contrasted to the data of KS, such differences could not be
      demonstrated. Based on our findings, specific management recommendations were
      discussed for each of the three syndromes. It is strongly suggested to consider
      the genetic origin in individuals with congenital neurodevelopmental disorders
      for individual based psychiatric and behavioral management.

PMID- 28498557
TI  - Preparation of Ultrathin Two-Dimensional Tix Ta1-x Sy Oz Nanosheets as Highly
      Efficient Photothermal Agents.
AB  - Although two-dimensional (2D) metal oxide/sulfide hybrid nanostructures have been
      synthesized, the facile preparation of ultrathin 2D nanosheets in high yield
      still remains a challenge. Herein, we report the first high-yield preparation of
      solution-processed ultrathin 2D metal oxide/sulfide hybrid nanosheets, that is,
      Tix Ta1-x Sy Oz (x=0.71, 0.49, and 0.30), from Tix Ta1-x S2 precursors. The
      nanosheet exhibits strong absorbance in the near-infrared region, giving a large
      extinction coefficient of 54.1 L g-1  cm-1 at 808 nm, and a high photothermal
      conversion efficiency of 39.2 %. After modification with lipoic acid-conjugated
      polyethylene glycol, the nanosheet is a suitable photothermal agent for treatment
      of cancer cells under 808 nm laser irradiation. This work provides a facile and
      general method for the preparation of 2D metal oxide/sulfide hybrid nanosheets.

PMID- 28498558
TI  - (E)-1,1,4,4-Tetramethyl-2-tetrazene (TMTZ): A Prospective Alternative to
      Hydrazines in Rocket Propulsion.
AB  - 1,1,4,4-Tetramethyl-2-tetrazene (TMTZ) is considered as a prospective replacement
      for toxic hydrazines used in liquid rocket propulsion. The heat of formation of
      TMTZ was computed and measured, giving values well above those of the hydrazines
      commonly used in propulsion. This led to a predicted maximum Isp of 337 s for
      TMTZ/N2 O4 mixtures, which is a value comparable to that of monomethylhydrazine.
      We found that TMTZ has a vapor pressure well below that of liquid hydrazines, and
      it is far less toxic. Finally, an improved synthesis is proposed, which is
      compatible with existing industrial production facilities after minor changes.
      TMTZ is thus an attractive liquid propellant candidate, with a performance
      comparable to hydrazines but a lower vapor pressure and toxicity.

PMID- 28498559
TI  - Altitude sickness and altitude adaptation.

PMID- 28498560
TI  - Deletion of alpha5 nicotine receptor subunits abolishes nicotinic aversive
      motivational effects in a manner that phenocopies dopamine receptor antagonism.
AB  - Nicotine addiction is a worldwide epidemic that claims millions of lives each
      year. Genetic deletion of alpha5 nicotinic acetylcholine receptor (nAChR)
      subunits has been associated with increased nicotine intake, however, it remains
      unclear whether acute nicotine is less aversive or more rewarding, and whether
      mice lacking the alpha5 nAChR subunit can experience withdrawal from chronic
      nicotine. We used place conditioning and conditioned taste avoidance paradigms to
      examine the effect of alpha5 subunit-containing nAChR deletion (alpha5 -/-) on
      conditioned approach and avoidance behaviour in nondependent and nicotine
      dependent and -withdrawn mice, and compared these motivational effects with those
      elicited after dopamine receptor antagonism. We show that nondependent alpha5 -/-
      mice find low, non-motivational doses of nicotine rewarding, and do not show an
      aversive conditioned response or taste avoidance to higher aversive doses of
      nicotine. Furthermore, nicotine-dependent alpha5 -/- mice do not show a
      conditioned aversive motivational response to withdrawal from chronic nicotine,
      although they continue to exhibit a somatic withdrawal syndrome. These effects
      phenocopy those observed after dopamine receptor antagonism, but are not
      additive, suggesting that alpha5 nAChR subunits act in the same pathway as
      dopamine and are critical for the experience of nicotine's aversive, but not
      rewarding motivational effects in both a nondependent and nicotine-dependent and 
      withdrawn motivational state. Genetic deletion of alpha5 nAChR subunits leads to
      a behavioural phenotype that exactly matches that observed after antagonizing
      dopamine receptors, thus we suggest that modulation of nicotinic receptors
      containing alpha5 subunits may modify dopaminergic signalling, suggesting novel
      therapeutic treatments for smoking cessation.

PMID- 28498561
TI  - Distinct dynamics and interaction patterns in H- and K-Ras oncogenic P-loop
      mutants.
AB  - Despite years of study, the structural or dynamical basis for the differential
      reactivity and oncogenicity of Ras isoforms and mutants remains unclear. In this
      study, we investigated the effects of amino acid variations on the structure and
      dynamics of wild type and oncogenic mutants G12D, G12V, and G13D of H- and K-Ras
      proteins. Based on data from us-scale molecular dynamics simulations, we show
      that the overall structure of the proteins remains similar but there are
      important differences in dynamics and interaction networks. We identified
      differences in residue interaction patterns around the canonical switch and
      distal loop regions, and persistent sodium ion binding near the GTP particularly
      in the G13D mutants. Our results also suggest that different Ras variants have
      distinct local structural features and interactions with the GTP, variations that
      have the potential to affect GTP release and hydrolysis. Furthermore, we found
      that H-Ras proteins and particularly the G12V and G13D variants are significantly
      more flexible than their K-Ras counterparts. Finally, while most of the simulated
      proteins sampled the effector-interacting state 2 conformational state, G12V and
      G13D H-Ras adopted an open switch state 1 conformation that is defective in
      effector interaction. These differences have implications for Ras GTPase
      activity, effector or exchange factor binding, dimerization and membrane
      interaction. Proteins 2017; 85:1618-1632. (c) 2017 Wiley Periodicals, Inc.

PMID- 28498563
TI  - Identification of factors associated with treatment refractoriness of oral
      lesions in pemphigus vulgaris.
AB  - BACKGROUND: The oral mucosal lesions of patients with pemphigus vulgaris are
      known to show more treatment refractoriness than skin lesions. OBJECTIVES: To
      identify which clinical and laboratory parameters may indicate treatment
      refractoriness of oral lesions in pemphigus vulgaris. METHODS: This was a
      prospective study of 50 adults with pemphigus vulgaris and oral lesions; patients
      were given treatment appropriate for overall disease severity. Treatment
      refractoriness was defined arbitrarily as less than 75% reduction in oral
      objective Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) after
      treatment for 6 months. RESULTS: Of 46 patients who completed the study, 17 (37%)
      were treatment refractory whereas 29 (63%) were treatment responsive. At
      baseline, the treatment refractory group had a significantly longer mean duration
      of disease (P = 0.02) and mean duration of oral lesions (P = 0.01), a higher
      percentage of lesions in the retromolar trigone (P = 0.05) and on the occlusion
      line along the buccal mucosa (P = 0.04), a higher percentage of deep/crateriform
      ulcers (P < 0.001) and erosions with a lichenoid hue (P < 0.001). Herpes simplex
      virus (HSV) DNA positivity, assessed by polymerase chain reaction in oral tissue
      scrapings (P = 0.02), was also significantly higher in the treatment refractory
      group. No other factors we tested for were statistically significant.
      CONCLUSIONS: Treatment refractoriness of oral lesions was significantly
      associated with duration of disease/oral lesions; specific morphology and
      location of oral lesions; and the presence of HSV DNA in the oral cavity. These
      factors may forewarn the treating physician about a refractory course of oral
      lesions that may help with counselling patients.

PMID- 28498562
TI  - Effect of valve design and anticoagulation strategy on 30-day clinical outcomes
      in transcatheter aortic valve replacement: Results from the BRAVO 3 randomized
      trial.
AB  - BACKGROUND: Selection of valve type and procedural anticoagulant may impact
      bleeding and vascular complications in transfemoral transcatheter aortic valve
      replacement (TAVR). We sought to compare outcomes by valve [balloon expandable
      (BE) or non-BE] and anticoagulant [bivalirudin vs. unfractionated heparin (UFH)]
      type from the BRAVO-3 trial. METHODS: BRAVO-3 was a randomized multicenter trial
      including 500 BE-TAVR and 282 non-BE TAVR patients, randomized to bivalirudin
      versus UFH. Selection of valve type was at the discretion of the operator but
      randomization was stratified according to valve type. Total follow up was to 30
      days. We examined the incidence of Bleeding Academic Research Consortium type
      >=3b bleeding, major vascular complications and all ischemic outcomes at 30-days.
      Outcomes were adjusted using logistic regression analysis. RESULTS: Of the trial
      cohort, 63.9% were treated with BE valves (n = 251 bivalirudin vs. n = 249 UFH)
      and 36.1% with non-BE valves (n = 140 bivalirudin vs. n = 142 UFH). Patients
      treated with non-BE valves were older, with higher euroSCORE I. At 30 days, there
      were nonsignificant differences between the two valve types for adjusted risk of
      all-cause death (HR 2.07, 95% CI 0.91-4.70, P = 0.084) and major vascular
      complications (HR 1.78, 95% CI 0.97-3.26, P = 0.062) with non-BE compared with BE
      valves, but all other outcomes were similar. A significant interaction was
      observed between valve and anticoagulant type, with lower risk of major vascular
      complications with bivalirudin compared with UFH in non-BE TAVR (P-interaction =
      0.039). CONCLUSIONS: Majority of patients in the BRAVO 3 trial received BE
      valves. At 30-days, adjusted risk of clinical outcomes was similar with non-BE
      vs. BE valves. A significant interaction was observed between valve type and
      procedural anticoagulant for lower risk of major vascular complications with
      bivalirudin versus UFH in non-BE TAVR.

PMID- 28498564
TI  - Spatial Bayesian latent factor regression modeling of coordinate-based meta
      analysis data.
AB  - Now over 20 years old, functional MRI (fMRI) has a large and growing literature
      that is best synthesised with meta-analytic tools. As most authors do not share
      image data, only the peak activation coordinates (foci) reported in the article
      are available for Coordinate-Based Meta-Analysis (CBMA). Neuroimaging meta
      analysis is used to (i) identify areas of consistent activation; and (ii) build a
      predictive model of task type or cognitive process for new studies (reverse
      inference). To simultaneously address these aims, we propose a Bayesian point
      process hierarchical model for CBMA. We model the foci from each study as a
      doubly stochastic Poisson process, where the study-specific log intensity
      function is characterized as a linear combination of a high-dimensional basis
      set. A sparse representation of the intensities is guaranteed through latent
      factor modeling of the basis coefficients. Within our framework, it is also
      possible to account for the effect of study-level covariates (meta-regression),
      significantly expanding the capabilities of the current neuroimaging meta
      analysis methods available. We apply our methodology to synthetic data and
      neuroimaging meta-analysis datasets.

PMID- 28498565
TI  - C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke
      in patients with atrial fibrillation: a more than 10-year prospective follow-up
      study.
AB  - : Essentials We studied the C-reactive protein (CRP) gene on stroke risk in
      atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism
      genotype were followed-up for more than 10 years. Patients with the A-390/T-390
      allele of the CRP gene were more likely to get ischemic stroke. The triallelic
      polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY:
      Background Little evidence is available regarding the impact of genetic
      polymorphisms on the risk of thromboembolic stroke in patients with atrial
      fibrillation (AF). An increasing body of evidence is demonstrating that
      inflammatory responses play an important role in the pathophysiology of AF.
      Objectives To investigate the effect of genetic polymorphisms of the C-reactive
      protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF.
      Methods A total of 725 AF patients were longitudinally followed up for > 10
      years; this is the largest and longest AF follow-up cohort with genetic data. CRP
      promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP
      levels were divided into four quartiles. Results Patients with higher CRP levels
      were more likely to develop thromboembolic stroke than those with lower CRP
      levels (P<0.001, log-rank test for comparison of four quartiles). After
      adjustment for conventional risk factors, patients with higher CRP levels were
      more likely to develop thromboembolic stroke than those in the lowest CRP
      quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the
      lowest CRP quartile was the reference group). Patients carrying the A-390 or T
      390 allele had higher CRP levels (3.35 +/- 2.71 mg L-1 versus 2.43 +/- 2.00 mg L
      1 ), and were more likely to develop thromboembolic stroke, even after adjustment
      for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP
      triallelic polymorphism and the CRP level are associated with the risk of
      incident thromboembolic stroke in patients with AF.

PMID- 28498566
TI  - Synergistic effects of fibronectin and bone morphogenetic protein on the
      bioactivity of titanium metal.
AB  - To improve the biological properties of bioactive titanium metal, recombinant
      human bone morphogenetic protein 2(rhBMP-2) and fibronectin (Fn) were adsorbed on
      its surface solely or contiguously to modify the anodic oxidized titanium (AO
      Ti), acid-alkali-treated titanium (AA-Ti), and polished titanium (P-Ti). It is
      found that the different bioactive titanium surface structures had great
      influence on protein adsorption. The adsorption amounts of BMP adsorbed solely
      and Fn/BMP adsorbed contiguously were AA-Ti > P-Ti > AO-Ti, and that for Fn
      adsorbed solely was AA-Ti ~ P-Ti > AO-Ti. The conformation of proteins was
      changed remarkably after the adsorption. For BMP, the alpha-helix decreased on AA
      Ti and stabilized on P-Ti and AO-Ti. For Fn, the beta-sheet on PT-Ti and AA-Ti
      increased significantly. For Fn/BMP, the percentage of beta-sheet on AA-Ti
      increased, and that of alpha-helix on all samples was stable. MSCs showed greater
      adhesion and spreading on Fn/BMP groups. MTT and Elisa tests showed that the
      synergistic effects of proteins made the cells proliferate and differentiate
      faster. It indicated both the surface structure and the synergistic effects of
      proteins could influence the biological properties of titanium metals. It
      provides research foundation for improving the biological properties of bioactive
      titanium metals by simultaneous application of several proteins. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2485-2498, 2017.

PMID- 28498567
TI  - Uterine fibroids: from observational epidemiology to clinical management.

PMID- 28498569
TI  - Report on WPA activities in the triennium 2014-2017.

PMID- 28498568
TI  - Reconstitution of immune cell populations in multiple sclerosis patients after
      autologous stem cell transplantation.
AB  - Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a
      Phase II clinical trial, high-dose immunosuppressive therapy combined with
      autologous CD34+ haematopoietic stem cell transplant resulted in 69.2% of
      subjects remaining disease-free without evidence of relapse, loss of neurological
      function or new magnetic resonance imaging (MRI) lesions to year 5 post
      treatment. A combination of CyTOF mass cytometry and multi-parameter flow
      cytometry was used to explore the reconstitution kinetics of immune cell subsets
      in the periphery post-haematopoietic cell transplant (HSCT) and the impact of
      treatment on the phenotype of circulating T cells in this study population.
      Repopulation of immune cell subsets progressed similarly for all patients studied
      2 years post-therapy, regardless of clinical outcome. At month 2, monocytes and
      natural killer (NK) cells were proportionally more abundant, while CD4 T cells
      and B cells were reduced, relative to baseline. In contrast to the changes
      observed at earlier time-points in the T cell compartment, B cells were
      proportionally more abundant and expansion in the proportion of naive B cells was
      observed 1 and 2 years post-therapy. Within the T cell compartment, the
      proportion of effector memory and late effector subsets of CD4 and CD8 T cells
      was increased, together with transient increases in proportions of CD45RA
      regulatory T cells (Tregs ) and T helper type 1 (Th1 cells) and a decrease in
      Th17.1 cells. While none of the treatment effects studied correlated with
      clinical outcome, patients who remained healthy throughout the 5-year study had
      significantly higher absolute numbers of memory CD4 and CD8 T cells in the
      periphery prior to stem cell transplantation.

PMID- 28498570
TI  - Migration and psychosis: our smoking lung?

PMID- 28498571
TI  - Shared decision making in mental health care settings: Perspective, purpose and
      practice.

PMID- 28498572
TI  - Drug use disorders: impact of a public health rather than a criminal justice
      approach.

PMID- 28498573
TI  - A reassessment of the relationship between depression and all-cause mortality in
      3,604,005 participants from 293 studies.

PMID- 28498574
TI  - Integrated care for mental, neurological and substance use disorders in non
      specialized health settings: rising to the challenge.

PMID- 28498575
TI  - Implementing shared decision making in routine mental health care.
AB  - Shared decision making (SDM) in mental health care involves clinicians and
      patients working together to make decisions. The key elements of SDM have been
      identified, decision support tools have been developed, and SDM has been
      recommended in mental health at policy level. Yet implementation remains limited.
      Two justifications are typically advanced in support of SDM. The clinical
      justification is that SDM leads to improved outcome, yet the available empirical
      evidence base is inconclusive. The ethical justification is that SDM is a right,
      but clinicians need to balance the biomedical ethical principles of autonomy and
      justice with beneficence and non-maleficence. It is argued that SDM is
      "polyvalent", a sociological concept which describes an idea commanding
      superficial but not deep agreement between disparate stakeholders. Implementing
      SDM in routine mental health services is as much a cultural as a technical
      problem. Three challenges are identified: creating widespread access to high
      quality decision support tools; integrating SDM with other recovery-supporting
      interventions; and responding to cultural changes as patients develop the normal
      expectations of citizenship. Two approaches which may inform responses in the
      mental health system to these cultural changes - social marketing and the
      hospitality industry - are identified.

PMID- 28498576
TI  - A critique of the "ultra-high risk" and "transition" paradigm.
AB  - The transdiagnostic expression of psychotic experiences in common mental disorder
      (anxiety/depression/substance use disorder) is associated with a poorer
      prognosis, and a small minority of people may indeed develop a clinical picture
      that meets criteria for schizophrenia. However, it appears neither useful nor
      valid to observe early states of multidimensional psychopathology in young people
      through the "schizo"-prism, and apply misleadingly simple, unnecessary and
      inefficient binary concepts of "risk" and "transition". A review of the "ultra
      high risk" (UHR) or "clinical high risk" (CHR) literature indicates that UHR/CHR
      samples are highly heterogeneous and represent individuals diagnosed with common
      mental disorder (anxiety/depression/substance use disorder) and a degree of
      psychotic experiences. Epidemiological research has shown that psychotic
      experiences are a (possibly non-causal) marker of the severity of
      multidimensional psychopathology, driving poor outcome, yet notions of "risk" and
      "transition" in UHR/CHR research are restrictively defined on the basis of
      positive psychotic phenomena alone, ignoring how baseline differences in
      multidimensional psychopathology may differentially impact course and outcome.
      The concepts of "risk" and "transition" in UHR/CHR research are measured on the
      same dimensional scale, yet are used to produce artificial diagnostic shifts. In
      fact, "transition" in UHR/CHR research occurs mainly as a function of variable
      sample enrichment strategies rather than the UHR/CHR "criteria" themselves.
      Furthermore, transition rates in UHR/CHR research are inflated as they do not
      exclude false positives associated with the natural fluctuation of dimensional
      expression of psychosis. Biological associations with "transition" thus likely
      represent false positive findings, as was the initial claim of strong effects of
      omega-3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR
      intervention research has focused on the questionable outcome of "transition",
      which shows lack of correlation with functional outcome. It may be more
      productive to consider the full range of person-specific psychopathology in all
      young individuals who seek help for mental health problems, instead of "policing"
      youngsters for the transdiagnostic dimension of psychosis. Instead of the
      relatively inefficient medical high-risk approach, a public health perspective,
      focusing on improved access to a low-stigma, high-hope, small scale and youth
      specific environment with acceptable language and interventions may represent a
      more useful and efficient strategy.

PMID- 28498577
TI  - News from WPA Scientific Sections.

PMID- 28498578
TI  - Why ultra high risk criteria for psychosis prediction do not work well outside
      clinical samples and what to do about it.

PMID- 28498579
TI  - Common sense alone is not enough.

PMID- 28498580
TI  - The role of expectations in mental disorders and their treatment.

PMID- 28498582
TI  - Mating, sexual selection, and the evolution of schizophrenia.

PMID- 28498581
TI  - The contemporary refugee crisis: an overview of mental health challenges.
AB  - There has been an unprecedented upsurge in the number of refugees worldwide, the
      majority being located in low-income countries with limited resources in mental
      health care. This paper considers contemporary issues in the refugee mental
      health field, including developments in research, conceptual models, social and
      psychological interventions, and policy. Prevalence data yielded by cross
      sectional epidemiological studies do not allow a clear distinction to be made
      between situational forms of distress and frank mental disorder, a shortcoming
      that may be addressed by longitudinal studies. An evolving ecological model of
      research focuses on the dynamic inter-relationship of past traumatic experiences,
      ongoing daily stressors and the background disruptions of core psychosocial
      systems, the scope extending beyond the individual to the conjugal couple and the
      family. Although brief, structured psychotherapies administered by lay
      counsellors have been shown to be effective in the short term for a range of
      traumatic stress responses, questions remain whether these interventions can be
      sustained in low-resource settings and whether they meet the needs of complex
      cases. In the ideal circumstance, a comprehensive array of programs should be
      provided, including social and psychotherapeutic interventions, generic mental
      health services, rehabilitation, and special programs for vulnerable groups.
      Sustainability of services, ensuring best practice, evidence-based approaches,
      and promoting equity of access must remain the goals of future developments, a
      daunting challenge given that most refugees reside in settings where skills and
      resources in mental health care are in shortest supply.

PMID- 28498583
TI  - Neuroticism is a fundamental domain of personality with enormous public health
      implications.

PMID- 28498585
TI  - Correction.

PMID- 28498584
TI  - Risk of suicide, deliberate self-harm and psychiatric illness after the loss of a
      close relative: A nationwide cohort study.
AB  - The loss of a close relative is a common event, yet it is associated with
      increased risk of serious mental health conditions. No large-scale study has
      explored up to now the importance of the bereaved person's relation to the
      deceased while accounting for gender and age. We performed a nationwide Danish
      cohort study using register information from 1995 through 2013 on four sub
      cohorts including all persons aged >=18 years exposed to the loss of a child,
      spouse, sibling or parent. We identified 1,445,378 bereaved persons, and each was
      matched by gender, age and family composition to five non-bereaved persons.
      Cumulative incidence proportions were calculated to estimate absolute differences
      in suicide, deliberate self-harm and psychiatric illness. Cox proportional hazard
      regression was used to calculate hazard ratios while adjusting for potential
      confounders. Results revealed that the risk of suicide, deliberate self-harm and
      psychiatric illness was increased in the bereaved cohorts for at least 10 years
      after the loss, particularly during the first year. During that year, the risk
      difference was 18.9 events in 1,000 persons after loss of a child (95% CI: 17.6
      20.1) and 16.0 events in 1,000 persons after loss of the spouse (95% CI: 15.4
      16.6). Hazard ratios were generally highest after loss of a child, in younger
      persons, and after sudden loss by suicide, homicide or accident. One in three
      persons with a previous psychiatric diagnosis experienced suicide, deliberate
      self-harm or psychiatric illness within the first year of bereavement. In
      conclusion, this study shows that the risk of suicide, deliberate self-harm and
      psychiatric illness is high after the loss of a close relative, especially in
      susceptible subgroups. This suggests the need for early identification of high
      risk persons displaying adjustment problems after loss of a close family member,
      in order to reduce the risk of serious mental health outcomes.

PMID- 28498586
TI  - Psychiatric practice: caring for patients, collaborating with partners, or
      marketing to consumers?

PMID- 28498587
TI  - Does neuroimaging have a role in predicting outcomes in psychosis?

PMID- 28498588
TI  - The clinical relevance of appraisals of psychotic experiences.

PMID- 28498589
TI  - Mental health shared decision making in the US.

PMID- 28498590
TI  - Validity and utility of the general factor of psychopathology.

PMID- 28498591
TI  - Has the rising placebo response impacted antidepressant clinical trial outcome?
      Data from the US Food and Drug Administration 1987-2013.
AB  - More than fifteen years ago, it was noted that the failure rate of antidepressant
      clinical trials was high, and such negative outcomes were thought to be related
      to the increasing magnitude of placebo response. However, there is considerable
      debate regarding this phenomenon and its relationship to outcomes in more recent
      antidepressant clinical trials. To investigate this, we accessed the US Food and
      Drug Administration (FDA) reviews for sixteen antidepressants (85 trials, 115
      trial arms, 23,109 patients) approved between 1987 and 2013. We calculated the
      magnitude of placebo and antidepressant responses, antidepressant-placebo
      differences, as well as the effect sizes and success rates, and compared these
      measures over time. Exploratory analysis investigated potential changes in trial
      design and conduct over time. As expected, the magnitude of placebo response has
      steadily grown in the past 30 years, increasing since 2000 by 6.4% (r=0.46,
      p<0.001). Contrary to expectations, a similar increase has occurred in the
      magnitude of antidepressant response (6.0%, r=0.37, p<0.001). Thus, the effect
      sizes (0.30 vs. 0.29, p=0.42) and the magnitude of antidepressant-placebo
      differences (10.5% vs. 10.3%, p=0.37) have remained statistically equivalent.
      Furthermore, the frequency of positive trial arms has gone up in the past 15
      years (from 47.8% to 63.8%), but this difference in frequency has not reached
      statistical significance. Trial design features that were previously associated
      with a possible lower magnitude of placebo response were not implemented, and
      their relationship to the magnitude of placebo response could not be replicated.
      Of the 34 recent trials, two implemented enhanced interview techniques, but both
      of them were unsuccessful. The results of this study suggest that the
      relationship between the magnitude of placebo response and the outcome of
      antidepressant clinical trials is weak at best. These data further indicate that
      antidepressant-placebo differences are about the same for all of the sixteen
      antidepressants approved by the FDA in the past thirty years.

PMID- 28498592
TI  - WPA International Competency-Based Curriculum for Mental Health Providers on
      Intimate Partner Violence and Sexual Violence Against Women.

PMID- 28498593
TI  - Involvement in decision making: the devil is in the detail.

PMID- 28498594
TI  - Persistent persecutory delusions: The spirit, style and content of targeted
      treatment.

PMID- 28498596
TI  - Shared decision making: everyone wants it, so why isn't it happening?

PMID- 28498595
TI  - Etiology in psychiatry: embracing the reality of poly-gene-environmental
      causation of mental illness.
AB  - Intriguing findings on genetic and environmental causation suggest a need to
      reframe the etiology of mental disorders. Molecular genetics shows that thousands
      of common and rare genetic variants contribute to mental illness. Epidemiological
      studies have identified dozens of environmental exposures that are associated
      with psychopathology. The effect of environment is likely conditional on genetic
      factors, resulting in gene-environment interactions. The impact of environmental
      factors also depends on previous exposures, resulting in environment-environment
      interactions. Most known genetic and environmental factors are shared across
      multiple mental disorders. Schizophrenia, bipolar disorder and major depressive
      disorder, in particular, are closely causally linked. Synthesis of findings from
      twin studies, molecular genetics and epidemiological research suggests that joint
      consideration of multiple genetic and environmental factors has much greater
      explanatory power than separate studies of genetic or environmental causation.
      Multi-factorial gene-environment interactions are likely to be a generic
      mechanism involved in the majority of cases of mental illness, which is only
      partially tapped by existing gene-environment studies. Future research may cut
      across psychiatric disorders and address poly-causation by considering multiple
      genetic and environmental measures across the life course with a specific focus
      on the first two decades of life. Integrative analyses of poly-causation
      including gene-environment and environment-environment interactions can realize
      the potential for discovering causal types and mechanisms that are likely to
      generate new preventive and therapeutic tools.

PMID- 28498597
TI  - Incorporating shared decision making in mental health care requires translating
      knowledge from implementation science.

PMID- 28498598
TI  - Prevention and early intervention for borderline personality disorder: a novel
      public health priority.

PMID- 28498600
TI  - Causes and predictors of premature death in first-episode schizophrenia spectrum
      disorders.

PMID- 28498601
TI  - Shared decision making: a consideration of historical and political contexts.

PMID- 28498602
TI  - Treatment of people at ultra-high risk for psychosis.

PMID- 28498599
TI  - Prevalence, incidence and mortality from cardiovascular disease in patients with
      pooled and specific severe mental illness: a large-scale meta-analysis of
      3,211,768 patients and 113,383,368 controls.
AB  - : People with severe mental illness (SMI) - schizophrenia, bipolar disorder and
      major depressive disorder - appear at risk for cardiovascular disease (CVD), but
      a comprehensive meta-analysis is lacking. We conducted a large-scale meta
      analysis assessing the prevalence and incidence of CVD; coronary heart disease;
      stroke, transient ischemic attack or cerebrovascular disease; congestive heart
      failure; peripheral vascular disease; and CVD-related death in SMI patients
      (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD
      prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4-13.3).
      Adjusting for a median of seven confounders, patients had significantly higher
      odds of CVD versus controls in cross-sectional studies (odds ratio, OR=1.53, 95%
      CI: 1.27-1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51,
      95% CI: 1.47-1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21-1.66).
      People with major depressive disorder were at increased risk for coronary heart
      disease, while those with schizophrenia were at increased risk for coronary heart
      disease, cerebrovascular disease and congestive heart failure. Cumulative CVD
      incidence in SMI patients was 3.6% (95% CI: 2.7-5.3) during a median follow-up of
      8.4 years (range 1.8-30.0). Adjusting for a median of six confounders, SMI
      patients had significantly higher CVD incidence than controls in longitudinal
      studies (hazard ratio, HR=1.78, 95% CI: 1.60-1.98; 31 studies). The incidence was
      also higher for coronary heart disease (HR=1.54, 95% CI: 1.30-1.82),
      cerebrovascular disease (HR=1.64, 95% CI: 1.26-2.14), congestive heart failure
      (HR=2.10, 95% CI: 1.64-2.70), and CVD-related death (HR=1.85, 95% CI: 1.53-2.24).
      People with major depressive disorder, bipolar disorder and schizophrenia were
      all at increased risk of CVD-related death versus controls. CVD incidence
      increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and
      higher baseline CVD prevalence (p=0.03) in patients vs. CONTROLS: Moreover, CVD
      prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently
      conducted studies. This large-scale meta-analysis confirms that SMI patients have
      significantly increased risk of CVD and CVD-related mortality, and that elevated
      body mass index, antipsychotic use, and CVD screening and management require
      urgent clinical attention.

PMID- 28498603
TI  - Calciphylaxis in haemodialysed patients: diagnostic value of calcifications in
      cutaneous biopsy.

PMID- 28498604
TI  - Postoperative interventions to reduce inflammatory complications after third
      molar surgery: review of the current evidence.
AB  - Inflammatory complications such as pain, swelling, trismus, infection and
      alveolar osteitis have an adverse affect on the quality of life of patients after
      third molar removal. This review presents the current evidence on postoperative
      strategies to reduce these complications. A literature search was performed to
      identify articles published in English between 2000 to 2016 using the following
      keywords: third molar(s), wisdom tooth/teeth, pain, swelling, trismus, infection,
      alveolar osteitis and dry socket. In total, 221 papers were reviewed. Methods
      published included analgesics, antibiotics, corticosteroids, mouthwashes, topical
      gels, cryotherapy and ozone therapy. This review highlights the variability in
      evidence available and summarizes the findings from best-quality evidence. In
      conclusion, paracetamol and ibuprofen are efficacious in managing postoperative
      pain. Corticosteroids and antibiotics should only be used in selected cases.
      Chlorhexidine reduces alveolar osteitis. The benefits of cryotherapy,
      postoperative irrigation and ozone gel are yet to be established.

PMID- 28498605
TI  - Brain structural connectivity and context-dependent extinction memory.
AB  - BACKGROUND: Extinction of conditioned fear represents an important mechanism in
      the treatment of anxiety disorders. Return of fear after successful extinction or
      exposure therapy in patients with anxiety disorders might be linked to poor
      temporal or contextual generalization of extinction due to individual differences
      in brain structural connectivity. The goal of this magnetic resonance imaging
      study was therefore to investigate the association of context-dependent
      extinction recall with brain structural connectivity. METHODS: Diffusion-tensor
      imaging was used to determine the fractional anisotropy as a measure of white
      matter structural integrity of fiber tracts connecting central brain regions of
      the fear and extinction circuit (uncinate fasciculus, cingulum). Forty-five
      healthy men participated in a two-day fear conditioning experiment with fear
      acquisition in context A and extinction learning in context B on the first day.
      Extinction recall in the extinction context as well as renewal in the acquisition
      context and a novel context C took place one day later. RESULTS: Renewal of
      conditioned fear (skin conductance responses) in the acquisition context was
      associated with higher structural integrity of the hippocampal part of the
      cingulum. CONCLUSIONS: Enhanced structural integrity of the cingulum might be
      related to stronger hippocampal modulation of the dorsal anterior cingulate
      cortex, a region important for modulating conditioned fear output by excitatory
      projections to the amygdala. This finding underpins the crucial role of
      individual differences in the structural integrity of relevant fiber tracts for
      context-dependent extinction recall and return of fear after exposure therapy in
      anxiety disorders.

PMID- 28498606
TI  - Is uvulopalatopharyngoplasty effective in obstructive sleep apnea?

PMID- 28498608
TI  - Computed tomography scanning in mycosis fungoides: optimizing the balance between
      benefit and harm.

PMID- 28498607
TI  - Human hepatocellular carcinomas with a periportal phenotype have the lowest
      potential for early recurrence after curative resection.
AB  - : Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes,
      raising major challenges in clinical management. HCCs detected by surveillance
      programs at an early stage are candidates for potentially curative therapies
      (local ablation, resection, or transplantation). In the long term,
      transplantation provides the lowest recurrence rates. Treatment allocation is
      based on tumor number, size, vascular invasion, performance status, functional
      liver reserve, and the prediction of early (<2 years) recurrence, which reflects
      the intrinsic aggressiveness of the tumor. Well-differentiated, potentially low
      aggressiveness tumors form the heterogeneous molecular class of nonproliferative
      HCCs, characterized by an approximate 50% beta-catenin mutation rate. To define
      the clinical, pathological, and molecular features and the outcome of
      nonproliferative HCCs, we constructed a 1,133-HCC transcriptomic metadata set and
      validated findings in a publically available 210-HCC RNA sequencing set. We show
      that nonproliferative HCCs preserve the zonation program that distributes
      metabolic functions along the portocentral axis in normal liver. More precisely,
      we identified two well-differentiated, nonproliferation subclasses, namely
      periportal-type (wild-type beta-catenin) and perivenous-type (mutant beta
      catenin), which expressed negatively correlated gene networks. The new periportal
      type subclass represented 29% of all HCCs; expressed a hepatocyte nuclear factor
      4A-driven gene network, which was down-regulated in mouse hepatocyte nuclear
      factor 4A knockout mice; were early-stage tumors by Barcelona Clinic Liver
      Cancer, Cancer of the Liver Italian Program, and tumor-node-metastasis staging
      systems; had no macrovascular invasion; and showed the lowest metastasis-specific
      gene expression levels and TP53 mutation rates. Also, we identified an eight-gene
      periportal-type HCC signature, which was independently associated with the
      highest 2-year recurrence-free survival by multivariate analyses in two
      independent cohorts of 247 and 210 patients. CONCLUSION: Well-differentiated HCCs
      display mutually exclusive periportal or perivenous zonation programs. Among all
      HCCs, periportal-type tumors have the lowest intrinsic potential for early
      recurrence after curative resection. (Hepatology 2017;66:1502-1518).

PMID- 28498609
TI  - Cytologic diagnosis of mammary neoplastic and non-neoplastic diseases in dogs.

PMID- 28498610
TI  - Diabetes distress is linked with worsening diabetes management over time in
      adults with Type 1 diabetes.
AB  - AIM: To determine the cross-sectional and longitudinal associations between
      diabetes distress and diabetes management. METHODS: In a non-interventional
      study, 224 adults with Type 1 diabetes were assessed for diabetes distress,
      missed insulin boluses, hypoglycaemic episodes, and HbA1c at baseline and 9
      months. RESULTS: At baseline, greater distress was associated with higher HbA1c
      and a greater percentage of missed insulin boluses. Longitudinally, elevated
      baseline distress was related to increased missed insulin boluses, and decreases
      in distress were associated with decreases in HbA1c . In supplementary analyses,
      neither depression symptoms nor a diagnosis of major depressive disorder was
      associated with missed insulin boluses, HbA1c or hypoglycaemic episodes in cross
      sectional or longitudinal analyses. CONCLUSIONS: Significant cross-sectional and
      longitudinal associations were found between diabetes distress and management; in
      contrast, no parallel associations were found for major depressive disorder or
      depression symptoms. Findings suggest that elevated distress may lead to more
      missed insulin boluses over time, suggesting a potential intervention target. The
      covarying association between distress and HbA1c points to the complex and likely
      interactive associations between these constructs. Findings highlight the need to
      address distress as an integral part of diabetes management in routine care.

PMID- 28498611
TI  - Design, Synthesis, and Biological Evaluation of Peptidomimetic N-Substituted Cbz
      4-Hyp-Hpa-Amides as Novel Inhibitors of Plasmodium falciparum.
AB  - A new series of peptidomimetic N-substituted Cbz-4-Hyp-Hpa-amides were designed,
      synthesized, and evaluated for inhibition of the Plasmodium falciparum.
      Substituents on the N-atom of the amide group were selected alkyl-, allyl-, aryl
      , 2-hydroxyethyl-, 2-cyanoethyl-, cyanomethyl-, 2-hydroxyethyl-, 2,2
      diethoxyethyl-, or 2-ethoxy-2-oxoethylamino groups, and about of 40 new compounds
      were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial
      activity has been investigated as for the final peptide mimetics, and their
      immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4
      hydroxyproline residue and 18 derivatives exhibited toxicity against P.
      falciparum. Of these agents, compound 23e was shown to have potent antimalarial
      activity with IC50 528 ng/ml.

PMID- 28498612
TI  - Design of a modulated orthovoltage stereotactic radiosurgery system.
AB  - PURPOSE: To achieve stereotactic radiosurgery (SRS) dose distributions with sharp
      gradients using orthovoltage energy fluence modulation with inverse planning
      optimization techniques. METHODS: A pencil beam model was used to calculate dose
      distributions from an orthovoltage unit at 250 kVp. Kernels for the model were
      derived using Monte Carlo methods. A Genetic Algorithm search heuristic was used
      to optimize the spatial distribution of added tungsten filtration to achieve dose
      distributions with sharp dose gradients. Optimizations were performed for depths
      of 2.5, 5.0, and 7.5 cm, with cone sizes of 5, 6, 8, and 10 mm. In addition to
      the beam profiles, 4pi isocentric irradiation geometries were modeled to examine
      dose at 0.07 mm depth, a representative skin depth, for the low energy beams.
      Profiles from 4pi irradiations of a constant target volume, assuming maximally
      conformal coverage, were compared. Finally, dose deposition in bone compared to
      tissue in this energy range was examined. RESULTS: Based on the results of the
      optimization, circularly symmetric tungsten filters were designed to modulate the
      orthovoltage beam across the apertures of SRS cone collimators. For each depth
      and cone size combination examined, the beam flatness and 80-20% and 90-10%
      penumbrae were calculated for both standard, open cone-collimated beams as well
      as for optimized, filtered beams. For all configurations tested, the modulated
      beam profiles had decreased penumbra widths and flatness statistics at depth.
      Profiles for the optimized, filtered orthovoltage beams also offered decreases in
      these metrics compared to measured linear accelerator cone-based SRS profiles.
      The dose at 0.07 mm depth in the 4pi isocentric irradiation geometries was higher
      for the modulated beams compared to unmodulated beams; however, the modulated
      dose at 0.07 mm depth remained <0.025% of the central, maximum dose. The 4pi
      profiles irradiating a constant target volume showed improved statistics for the
      modulated, filtered distribution compared to the standard, open cone-collimated
      distribution. Simulations of tissue and bone confirmed previously published
      results that a higher energy beam (>= 200 keV) would be preferable, but the 250
      kVp beam was chosen for this work because it is available for future
      measurements. CONCLUSIONS: A methodology has been described that may be used to
      optimize the spatial distribution of added filtration material in an orthovoltage
      SRS beam to result in dose distributions with decreased flatness and penumbra
      statistics compared to standard open cones. This work provides the mathematical
      foundation for a novel, orthovoltage energy fluence-modulated SRS system.

PMID- 28498613
TI  - A Series of Bimetallic Ammonium AlNa Formates.
AB  - A series of AlNa bimetallic ammonium metal formate frameworks (AlNa AMFFs) have
      been prepared by employing various ammoniums from NH4+ to large linear
      polyammoniums. The series consists of six perovskites of (412 ?63 ) topology for
      mono-ammoniums, two chiral (49 ?66 ) frameworks incorporating polyethylene
      ammoniums, two niccolites with (412 ?63 )(49 ?66 ) topology containing
      diammoniums, and two layered compounds made of 2D (4,4) AlNa formate sheets
      intercalated by small diammoniums. The first ten compounds present the structural
      hierarchy of (412 ?63 )m (49 ?66 )n framework topologies for (m, n)=(1, 0), (0,
      1), and (1, 1), respectively, in parallel to the homometallic AMFFs for divalent
      metals. The symmetry lowering, asymmetric formate bridges, and different hydrogen
      bonding strengths appeared in the bimetallic structures owing to the different
      charge and size of Al3+ and Na+ seemingly inhibits the occurrence of phase
      transitions for more than half the AlNa AMFFs within the series, and the
      bimetallic members undergoing phase transitions show different transition
      behaviors and dielectric properties compared with the homometallic analogs.
      Anisotropic/negative/zero thermal expansions of the materials could be rationally
      attributed to the librational motion, or flip movement between different sites,
      of the ammonium cations, and the coupled change of AlNa formate frameworks. The
      thermal and IR spectroscopic properties have also been investigated.

PMID- 28498615
TI  - Understanding the impact of haemodialysis on UK National Health Service patients'
      well-being: A qualitative investigation.
AB  - AIMS AND OBJECTIVES: While haemodialysis is an effective treatment for end-stage
      renal disease, the requirements and restrictions it imposes on patients can be
      onerous. The aim of this study was to obtain UK National Health Service patients'
      perspectives on the challenges arising from haemodialysis with the intention of
      identifying potential improvements. BACKGROUND: Depression rates are particularly
      high in those with end-stage renal disease; however, there is limited insight
      into the range of stressors associated with haemodialysis treatment within the
      National Health Service contributing to such high rates, particularly those of a
      cognitive or psychological nature. DESIGN: A qualitative approach was used to
      obtain rich, patient-focused data; one-to-one semi-structured interviews were
      conducted with twenty end-stage renal disease at a UK National Health Service
      centre. METHODS: Patients were interviewed during a typical haemodialysis
      session. Thematic analysis was used to systematically interpret the data. Codes
      were created in an inductive and cyclical process using a constant comparative
      approach. RESULTS: Three themes emerged from the data: (i) fluctuations in
      cognitive/physical well-being across the haemodialysis cycle, (ii) restrictions
      arising from the haemodialysis treatment schedule, (iii) emotional impact of
      haemodialysis on the self and others. The findings are limited to predominantly
      white, older patients (median = 74 years) within a National Health Service
      setting. CONCLUSIONS: Several of the experiences reported by patients as
      challenging and distressing have so far been overlooked in the literature. A
      holistic-based approach to treatment, acknowledging all aspects of a patient's
      well-being, is essential if optimal quality of life is to be achieved by
      healthcare providers. RELEVANCE TO CLINICAL PRACTICE: The findings can be used to
      inform future interventions and guidelines aimed at improving patients' treatment
      adherence and outcomes, for example, improved reliable access to mental health
      specialists.

PMID- 28498616
TI  - Tethering Formation to Resorption: Reversal Revisited.

PMID- 28498614
TI  - Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate
      cotransporting polypeptide and organic anion transporting polypeptides and
      modulated by intestinal sensing of plasma bile acid levels in mice.
AB  - : The Na+ -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to
      be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid
      levels are normal in a subset of NTCP knockout mice and in mice treated with
      myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport
      proteins mediate the hepatic uptake of conjugated bile acids and demonstrated
      intestinal sensing of elevated bile acid levels in plasma in mice. Mice or
      healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake
      kinetics were determined in wild-type (WT), organic anion transporting
      polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1
      transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic
      transporter mRNA levels were assessed in rat hepatoma cells and in mice by
      peptide injection or adeno-associated virus-mediated overexpression. NTCP
      inhibition using myrcludex B had only moderate effects on bile acid kinetics in
      WT mice, but completely inhibited active transport of conjugated bile acid
      species in OATP knockout mice. Cholesterol 7alpha-hydroxylase Cyp7a1 expression
      was strongly down-regulated upon prolonged inhibition of hepatic uptake of
      conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced
      in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated
      cholestatic mice, whereas plasma FGF19 was not induced in humans treated with
      myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte
      models and mouse organoids by basolateral incubation with a high concentration (1
      mM) of conjugated bile acids. CONCLUSION: NTCP and OATPs contribute to hepatic
      uptake of conjugated bile acids in mice, whereas the predominant uptake in humans
      is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile
      acids in the systemic circulation to induce FGF15/19, which modulates hepatic
      bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643).

PMID- 28498617
TI  - Segmental resection is a safe oncological alternative to total proctocolectomy in
      elderly patients with ulcerative colitis and malignancy.
AB  - AIM: The standard approach for the surgical management of colorectal cancer (CRC)
      in the setting of ulcerative colitis (UC) involves total proctocolectomy (TPC).
      However, some patients also undergo a partial resection (PR). This may be an
      attractive option in older patients with a high risk for surgery. The aim of this
      study was to compare the risk of metachronous cancer after PR or TPC for CRC in
      the setting of UC. METHOD: This was a retrospective cohort study conducted
      through the Nationwide Veterans Affairs Healthcare System (VA). Patients who had
      UC and underwent a PR or TPC for CRC were followed from the time of their surgery
      to their most recent clinical follow-up. The primary outcome was development of
      metachronous cancer in the PR group. Secondary outcomes included surgical and
      medical outcomes. RESULTS: Fifty-nine patients were included: 24 (40.7%)
      underwent PR and 35 (59.3%) underwent TPC. The median age at cancer diagnosis was
      73.0 and 61.7 years in PR and TPC groups, respectively (P < 0.0005). Amongst
      patients undergoing PR, 15 (60%) had no active UC at the time of surgery, whereas
      in patients undergoing TPC, at the time of surgery eight (23.5%) had no active UC
      (P = 0.005). No patient who underwent a partial colectomy developed a
      metachronous cancer in the retained colonic segment during the follow-up period
      (median 7 years). CONCLUSION: Our study suggests that PR for CRC in the setting
      of UC may be a viable option in a selected cohort of patients, especially among
      the elderly.

PMID- 28498619
TI  - Race.

PMID- 28498618
TI  - Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination
      for castration resistant prostate cancer.
AB  - Cell division associated 1 (CDCA1) was screened as an oncogene that is
      overexpressed on several cancers, including prostate cancer. A highly immunogenic
      HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein
      was also identified. A phase I clinical trial was conducted for patients with
      castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination.
      Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel
      chemotherapy were enrolled. They received subcutaneous administration of the
      CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose
      escalation manner (doses of 1.0 or 3.0 mg/body, six patients received each dose).
      The primary endpoint was safety, and the secondary endpoints were the
      immunological and clinical responses. Vaccination with CDCA1 peptide was well
      tolerated without any serious adverse events. Peptide-specific cytotoxic T
      lymphocyte (CTL) responses using ELISPOT assay and dextramer assay were observed
      in three patients receiving the 1.0 mg dose and five patients receiving the 3.0
      mg dose. The median overall survival time was 11.0 months and specific CTL
      reacting to CDCA1 peptide were recognized in long-surviving patients. CDCA1
      derived peptide vaccine treatment was tolerable and might effectively induce
      peptide-specific CTLs for CRPC patients. This novel peptide vaccine therapy for
      CRPC appears promising. (ClinicalTrials.gov number, NCT01225471).

PMID- 28498620
TI  - Ultrahigh Thermal Conductive yet Superflexible Graphene Films.
AB  - Electrical devices generate heat at work. The heat should be transferred away
      immediately by a thermal manager to keep proper functions, especially for high
      frequency apparatuses. Besides high thermal conductivity (K), the thermal manager
      material requires good foldability for the next generation flexible electronics.
      Unfortunately, metals have satisfactory ductility but inferior K (<=429 W m-1 K-1
      ), and highly thermal-conductive nonmetallic materials are generally brittle.
      Therefore, fabricating a foldable macroscopic material with a prominent K is
      still under challenge. This study solves the problem by folding atomic thin
      graphene into microfolds. The debris-free giant graphene sheets endow graphene
      film (GF) with a high K of 1940 +/- 113 W m-1 K-1 . Simultaneously, the
      microfolds render GF superflexible with a high fracture elongation up to 16%,
      enabling it more than 6000 cycles of ultimate folding. The large-area
      multifunctional GFs can be easily integrated into high-power flexible devices for
      highly efficient thermal management.

PMID- 28498621
TI  - Enhanced production of enveloped viruses in BST-2-deficient cell lines.
AB  - Despite all the advantages that cell-cultured influenza vaccines have over egg
      based influenza vaccines, the inferior productivity of cell-culture systems is a
      major drawback that must be addressed. BST-2 (tetherin) is a host restriction
      factor which inhibits budding-out of various enveloped viruses from infected host
      cells. We developed BST-2-deficient MDCK and Vero cell lines to increase
      influenza virus release in cell culture. BST-2 gene knock-out resulted in
      increased release of viral particles into the culture medium, by at least 2-fold
      and up to 50-fold compared to release from wild-type counterpart cells depending
      on cell line and virus type. The effect was not influenza virus/MDCK/Vero
      specific, but was also present in a broad range of host cells and virus families;
      we observed similar results in murine, human, canine, and monkey cell lines with
      viruses including MHV-68 (Herpesviridae), influenza A virus (Orthomyxoviridae),
      porcine epidemic diarrhea virus (Coronaviridae), and vaccinia virus (Poxviridae).
      Our results suggest that the elimination of BST-2 expression in virus-producing
      cell lines can enhance the production of viral vaccines. Biotechnol.
      Bioeng.2017;114: 2289-2297. (c) 2017 Wiley Periodicals, Inc.

PMID- 28498622
TI  - Regulation of RAW264.7 macrophage polarization on smooth and rough surface
      topographies by galectin-3.
AB  - Recognition of topographical features induces phenotypic changes in macrophages
      although the receptors and signaling pathways are not completely characterized.
      As integrin molecules in focal adhesions/podosomes are in intimate contact with
      topography and topography modulates the NFkB pathway through cholesterol enriched
      raft-associated adhesive signaling structures we hypothesized that a cell-surface
      signaling complex comprised of galectin-3 together with its ligand CD98 and
      integrinbeta1 is important for topography-directed lineage determination. This
      study used polished, sand blasted and acid etched (SLA) surfaces and two novel
      grooved topographies (G1 and G2) produced by anisotropic etching of Si <1 1 0> to
      evaluate the role of galectin-3 in macrophage polarization in RAW 264.7
      macrophages, as determined by gene expression and morphology. In the presence of
      the galectin-3 inhibitor, lactose, the M2 marker (mannose receptor) was down
      regulated while the M1 marker (iNOS) was up-regulated on smooth and rough
      surfaces. This skewing of phenotype suggests a role for galectin-3 in macrophage
      polarization towards the M2 phenotype. Additionally, we evaluated the role of
      PI3K on polarization using PI3K inhibitor LY294002. We found that the M2 marker
      was down-regulated on both PO (surface polished) and G1 surfaces implicating PI3K
      in lineage determination. We also found that surface topography altered cell
      morphology; macrophages had a larger area on G2 surfaces. Lactose treatment
      significantly reduced the cell area on all topographies suggesting that the
      galectin-3 is also involved in signaling complexes triggering the rearrangement
      of the actin cytoskeleton. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 105A: 2499-2509, 2017.

PMID- 28498623
TI  - Interplay of Electronic Cooperativity and Exchange Coupling in Regulating the
      Reactivity of Diiron(IV)-oxo Complexes towards C-H and O-H Bond Activation.
AB  - Activation of inert C-H bonds such as those of methane are extremely challenging
      for chemists but in nature, the soluble methane monooxygenase (sMMO) enzyme
      readily oxidizes methane to methanol by using a diiron(IV) species. This has
      prompted chemists to look for similar model systems. Recently, a (MU-oxo)bis(MU
      carboxamido)diiron(IV) ([FeIV2 O(L)2 ]2+ L=N,N-bis-(3',5'-dimethyl-4'
      methoxypyridyl-2'-methyl)-N'-acetyl-1,2-diaminoethane) complex has been generated
      by bulk electrolysis and this species activates inert C-H bonds almost 1000 times
      faster than mononuclear FeIV =O species and at the same time selectively
      activates O-H bonds of alcohols. The very high reactivity and selectivity of this
      species is puzzling and herein we use extensive DFT calculations to shed light on
      this aspect. We have studied the electronic and spectral features of diiron
      {FeIII -MU(O)-FeIII }+2 (complex I), {FeIII -MU(O)-FeIV }+3 (II), and {FeIV 
      MU(O)-FeIV }+4 (III) complexes. Strong antiferromagnetic coupling between the Fe
      centers leads to spin-coupled S=0, S=3/2, and S=0 ground state for species I-III
      respectively. The mechanistic study of the C-H and O-H bond activation reveals a
      multistate reactivity scenario where C-H bond activation is found to occur
      through the S=4 spin-coupled state corresponding to the high-spin state of
      individual FeIV centers. The O-H bond activation on the other hand, occurs
      through the S=2 spin-coupled state corresponding to an intermediate state of
      individual FeIV centers. Molecular orbital analysis reveals sigma-pi/pi-pi
      channels for the reactivity. The nature of the magnetic exchange interaction is
      found to be switched during the course of the reaction and this offers lower
      energy pathways. Significant electronic cooperativity between two metal centers
      during the course of the reaction has been witnessed and this uncovers the reason
      behind the efficiency and selectivity observed. The catalyst is found to
      prudently choose the desired spin states based on the nature of the substrate to
      effect the catalytic transformations. These findings suggest that the presence of
      such factors play a role in the reactivity of dinuclear metalloenzymes such as
      sMMO.

PMID- 28498624
TI  - Additional benefit of using a risk-based selection for prostate biopsy: an
      analysis of biopsy complications in the Rotterdam section of the European
      Randomized Study of Screening for Prostate Cancer.
AB  - OBJECTIVE: To investigate biopsy complications and hospital admissions that could
      be reduced by the use of European Randomized Study of Screening for Prostate
      Cancer (ERSPC) risk calculators. MATERIALS AND METHODS: All biopsies performed in
      the Rotterdam section of the ERSPC between 1993 and 2015 were included. Biopsy
      complications and hospital admission data were prospectively recorded in
      questionnaires that were completed 2 weeks after biopsy. The ERSPC risk
      calculators 3 (RC3) and 4 (RC4) were applied to men attending the first and
      subsequent rounds of screening, respectively. Applying the predefined RC3/4
      probability thresholds for prostate cancer (PCa) risk of >=12.5% and high-grade
      PCa risk >=3%, we assessed the number of complications, admissions and costs that
      could be reduced by avoiding biopsies in men below these thresholds. RESULTS: A
      total of 10 747 biopsies with complete questionnaires were included. For these
      biopsies a complication rate of 67.9% (7294/10 747), a post-biopsy fever rate of
      3.9% (424/10747) and a hospital admission rate of 0.9% (92/10747) were recorded.
      The fever rate was found to be static over the years, but the hospital admission
      rate tripled from 0.6% (1993-1996) to 2.1% (2009-2015). Among 7704 biopsies which
      fit the criteria for RC3 or RC4, 35.8% of biopsies (2757/7704), 37.4% of
      complications (1972/5268), 39.4% of fever events (128/325) and 42.3% of
      admissions (30/71) could have been avoided by using one of the risk calculators.
      More complications could have been avoided if RC4 had been used and for more
      recent biopsies (2009-2015). Our findings show that 35.9% of the total cost of
      biopsies and complication treatment could have been avoided. CONCLUSION: A
      significant proportion of biopsy complications, hospital admissions and costs
      could be reduced if biopsy decisions were based on ERSPC risk calculators instead
      of PSA only. This effect was most prominent in more recent biopsies and in men
      with repeated biopsies or screening.

PMID- 28498625
TI  - Biomechanics of the human uterus.
AB  - The appropriate biomechanical function of the uterus is required for the
      execution of human reproduction. These functions range from aiding the transport
      of the embryo to the implantation site, to remodeling its tissue walls to host
      the placenta, to protecting the fetus during gestation, to contracting forcefully
      for a safe parturition and postpartum, to remodeling back to its nonpregnant
      condition to renew the cycle of menstruation. To serve these remarkably diverse
      functions, the uterus is optimally geared with evolving and contractile muscle
      and tissue layers that are cued by chemical, hormonal, electrical, and mechanical
      signals. The relationship between these highly active biological signaling
      mechanisms and uterine biomechanical function is not completely understood for
      normal reproductive processes and pathological conditions such as adenomyosis,
      endometriosis, infertility and preterm labor. Animal studies have illuminated the
      rich structural function of the uterus, particularly in pregnancy. In humans,
      medical imaging techniques in ultrasound and magnetic resonance have been
      combined with computational engineering techniques to characterize the uterus in
      vivo, and advanced experimental techniques have explored uterine function using
      ex vivo tissue samples. The collective evidence presented in this review gives an
      overall perspective on uterine biomechanics related to both its nonpregnant and
      pregnant function, highlighting open research topics in the field. Additionally,
      uterine disease and infertility are discussed in the context of tissue injury and
      repair processes and the role of computational modeling in uncovering etiologies
      of disease. WIREs Syst Biol Med 2017, 9:e1388. doi: 10.1002/wsbm.1388 For further
      resources related to this article, please visit the WIREs website.

PMID- 28498626
TI  - Risk of labor dystocia increases with maternal age irrespective of parity: a
      population-based register study.
AB  - INTRODUCTION: Advanced maternal age is associated with labor dystocia (LD) in
      nulliparous women. This study investigates the age-related risk of LD in first,
      second and third births. MATERIAL AND METHODS: All live singleton cephalic births
      at term (>= 37 gestational weeks) recorded in the Swedish Medical Birth Register
      from 1999 to 2011, except elective cesarean sections and fourth births and more,
      in total 998 675 pregnancies, were included in the study. LD was defined by
      International Classification of Diseases, version 10 codes (O620, O621, O622,
      O629, O630, O631 and O639). In each parity group risks of LD at age 25-29 years,
      30-34 years, 35-39 years and >= 40 years compared with age < 25 years were
      investigated by logistic regression analyses. Analyses were adjusted for year of
      delivery, education, country/region of birth, smoking in early pregnancy,
      maternal height, body mass index, week of gestation, fetal presentation and
      infant birthweight. RESULTS: Rates of LD were 22.5%, 6.1% and 4% in first, second
      and third births, respectively. Adjusted odd ratios (OR) for LD increased
      progressively from the youngest to the oldest age group, irrespective of parity.
      At age 35-39 years the adjusted OR (95% CI) was approximately doubled compared
      with age 25 and younger: 2.13 (2.06-2.20) in first birth; 2.05 (1.91-2.19) in
      second births; and 1.81 (1.49-2.21) in third births. CONCLUSIONS: Maternal age is
      an independent risk factor for LD in first, second and third births. Although age
      related risks by parity are relatively similar, more nulliparous than parous
      women will be exposed to LD due to the higher rate.

PMID- 28498628
TI  - Erratum: High speed sCMOS-based oblique plane microscopy applied to the study of
      calcium dynamics in cardiac myocytes: [J. Biophotonics 9, No. 3, 311-323 (2016)].
AB  - In the article by M.B. Sikkel et al. (doi: 10.1002/jbio.201500193), published in
      J. Biophotonics 9, 311-323 (2016), an error occurred in the computer code that
      was used to generate Figure 3. This erratum is published to correct Figure 3, the
      calculated value of tgeom and the experimentally determined value of toptics in
      the text of the article.

PMID- 28498627
TI  - A UK community-based survey on the prevalence of rhinosinusitis.
AB  - OBJECTIVES: There is limited information about the prevalence of rhinosinusitis
      in the UK community. This study aimed to identify its prevalence and investigate
      any association with demographic variables. The secondary aims were to determine
      the degree of impairment, impact on quality of life and any costs incurred by
      patients. DESIGN: We used a modified version (MSNOT-20) of a quality-of-life
      instrument, the sinonasal outcome test-20 (SNOT-20), in a small and successful
      pilot project. It was then used in a community-based survey and a second phase 6
      months later to test repeatability. Nasal examination and comparison of its
      quality-of-life section with other health-related quality-of-life tools occurred
      in the second phase. SETTING AND PARTICIPANTS: The questionnaire was administered
      by post to 2000 Farnborough (UK) residents, selected through stratified
      randomisation. The relation of an abnormal MSNOT-20 score with hay fever, asthma,
      smoking, food allergy, work productivity and social limitation was also analysed.
      MAIN OUTCOME AND RESULTS: The response rate was 79.8%; over thirty per cent of
      the community suffer from upper respiratory tract symptoms with impact on
      multiple domains of quality of life including emotional, financial costs and loss
      of days at work. The MSNOT-20 provided a more sensitive assessment of health
      related quality of life than the Short Form 36 questionnaire. CONCLUSION:
      Rhinosinusitis is prevalent in the Farnborough community and associated with
      significant morbidity and impairment on quality of life. The MSNOT-20 is a useful
      disease-specific quality-of-life tool in rhinosinusitis.

PMID- 28498629
TI  - Biophotonics.World - More than just a news page: The largest biophotonics network
      worldwide.

PMID- 28498630
TI  - The "appropriateness" of AUC for peripheral arterial disease: The story
      continues....

PMID- 28498631
TI  - Marijuana Use in Pregnancy: Concerns in an Evolving Era.
AB  - Marijuana is the most commonly used illicit drug in pregnancy, and the prevalence
      of use during pregnancy is increasing in the United States. Although much of the
      existing research investigating marijuana use in pregnancy is limited by study
      design and confounding factors, a growing accumulation of data suggests adverse
      outcomes. Studies have identified associations with decreased birth weight,
      increased spontaneous preterm birth, and impaired neurodevelopment among children
      and adults with in utero exposure. Moderate concentrations of marijuana have also
      been identified in breast milk. Due to these findings, multiple professional
      societies have issued clear statements against marijuana use during pregnancy and
      lactation.

PMID- 28498632
TI  - Robotic microlaryngeal phonosurgery: Testing of a "steady-hand" microsurgery
      platform.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate gains in microlaryngeal precision achieved by
      using a novel robotic "steady hand" microsurgery platform in performing simulated
      phonosurgical tasks. STUDY DESIGN: Crossover comparative study of surgical
      performance and descriptive analysis of surgeon feedback. METHODS: A novel
      robotic ear, nose, and throat microsurgery system (REMS) was tested in simulated
      phonosurgery. Participants navigated a 0.4-mm-wide microlaryngeal needle through
      spirals of varying widths, both with and without robotic assistance. Fail time
      (time the needle contacted spiral edges) was measured, and statistical comparison
      was performed. Participants were surveyed to provide subjective feedback on the
      REMS. RESULTS: Nine participants performed the task at three spiral widths,
      yielding 27 paired testing conditions. In 24 of 27 conditions, robot-assisted
      performance was better than unassisted; five trials were errorless, all achieved
      with the robot. Paired analysis of all conditions revealed fail time of 0.769 +/-
      0.568 seconds manually, improving to 0.284 +/- 0.584 seconds with the robot (P =
      .003). Analysis of individual spiral sizes showed statistically better
      performance with the REMS at spiral widths of 2 mm (0.156 +/- 0.226 seconds vs.
      0.549 +/- 0.545 seconds, P = .019) and 1.5 mm (0.075 +/- 0.099 seconds vs. 0.890
      +/- 0.518 seconds, P = .002). At 1.2 mm, all nine participants together showed
      similar performance with and without robotic assistance (0.621 +/- 0.923 seconds
      vs. 0.868 +/- 0.634 seconds, P = .52), though subgroup analysis of five surgeons
      most familiar with microlaryngoscopy showed statistically better performance with
      the robot (0.204 +/- 0.164 seconds vs. 0.664 +/- 0.354 seconds, P = .036).
      CONCLUSIONS: The REMS is a novel platform with potential applications in
      microlaryngeal phonosurgery. Further feasibility studies and preclinical testing
      should be pursued as a bridge to eventual clinical use. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 128:126-132, 2018.

PMID- 28498633
TI  - How does radioactive iodine affect the nose?
AB  - OBJECTIVES/HYPOTHESIS: To determine the effect of radioactive iodine (RAI)
      treatment on the nasal mucosa and nasal functions. STUDY DESIGN: Prospective
      clinical study. METHODS: This study included 41 patients (31 female and 10 male)
      who were treated with RAI for papillary thyroid carcinoma. A visual analogue
      scale (VAS) was used for subjective evaluation of nasal symptoms. The saccharine
      test, nasal Schirmer test, and acoustic rhinometry were used for objective
      evaluation of nasal functions. All tests were administered at baseline (before
      RAI treatment), and then 1 month and 1 year post-RAI treatment. Only 21 of the
      patients could be evaluated after 1 year of treatment and were included in the
      study's analysis. RESULTS: VAS obstruction and dryness scores 1 month and 1 year
      post-RAI were significantly higher than the baseline scores (P < .05 and P < .05,
      respectively). Mean cross-sectional area values 1 month and 1 year post-RAI did
      not differ significantly from baseline values (P > .05 and P > .05,
      respectively). Schirmer test results 1 month and 1 year post-RAI treatment were
      significantly lower than at baseline (P < .05 and P < .05, respectively).
      Saccharine test results 1 month and 1 year post-RAI were significantly higher
      than at baseline (P < .05). CONCLUSIONS: RAI treatment can adversely affect the
      nasal mucosa. Nasal dryness and obstruction can occur immediately after RAI
      treatment. Additional research is warranted to further elucidate the effects of
      RAI treatment on nasal function. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2698
      2702, 2017.

PMID- 28498634
TI  - Older people with Type 2 diabetes, including those with chronic kidney disease or
      dementia, are commonly overtreated with sulfonylurea or insulin therapies.
AB  - AIM: To evaluate potential overtreatment with sulfonylurea and insulin therapies
      amongst older people with Type 2 diabetes, including those with chronic kidney
      disease or dementia. METHODS: Using the ECLIPSE Live software tool, we developed
      a search to examine data on older people (age >= 70 years) with Type 2 diabetes,
      who were prescribed sulfonylurea or insulin therapies over the previous 90 days.
      Sixteen Norfolk general practices participated, representing a population of 24
      661 older people, including 3862 (15.7%) with Type 2 diabetes. Of these, 1379
      (35.7%) people were prescribed sulfonylurea or insulin therapies. Data extracted
      included age, sex, last recorded HbA1c value, renal function and dementia codes.
      RESULTS: The median age of the study cohort was 78 years. A total of 644 people
      (47.8%) had chronic kidney disease (estimated GFR < 60 mL/min/1.73m2 ) and 60
      people (4.35%) had dementia. The median (interquartile range) HbA1c concentration
      for the entire cohort was 58 (51-69) mmol/mol [7.5 (6.8-8.5)%], with no
      difference in median HbA1c between those with or without either chronic kidney
      disease or dementia. In total, 400 older people (29.9%) had an HbA1c
      concentration < 53 mmol/mol (7%), of whom 162 (12.1%) had HbA1c < 48 mmol/mol
      (6.5%). Stratified by prescription for sulfonylurea, insulin or combined insulin
      and sulfonylurea therapies, 282 (35.2%), 93 (24.2%) and 25 people (16.3%),
      respectively, had HbA1c < 53 mmol/mol (7.0%). Treatment to an HbA1c target of <
      53 mmol/mol (7.0%) was as prevalent in those with chronic kidney disease or
      dementia as in those without. CONCLUSION: In the present cohort of older people
      with Type 2 diabetes prescribed sulfonylurea or insulin therapies, overtreatment
      was common, even in the presence of comorbidities known to increase hypoglycaemia
      risk.

PMID- 28498635
TI  - SNX10 Plays a Critical Role in MMP9 Secretion via JNK-p38-ERK Signaling Pathway.
AB  - Matrix metalloproteinases (MMPs) plays a critical role in the degradation of
      extracellular matrix (ECM). Sorting nexin (SNX) 10 is a member of the SNX family,
      which functions in regulation of endosomal sorting and osteoclast activation, has
      been implicated to play an important role in the bone erosion of rheumatoid
      arthritis. In this study, we aimed to investigate the possible role of SNX10 on
      MMP9 secretion and the potential mechanism. By immunostaining and co
      immunoprecipitation, we found that SNX10 was extensively co-localized with MMP9,
      indicating that SNX10 might participate in MMP9 trafficking. After knocking down
      SNX10 via siRNA, the secretion and activity of MMP9 was significantly reduced,
      but the amount of protein was increased. By contraries, over-expression of SNX10
      could increase the secretion and activity levels. Deficiency of SNX10 impaired
      the differentiation and bone resorption function of osteoclast, with a low
      activity of MMP9 compared to WT one. In SNX10 knockout osteoclast, the
      phosphorylation levels of JNK, p38, and ERK were obviously down-regulated. Our
      results first identified the role of SNX10 in MMP9 trafficking and secretion, and
      provided an evidence for SNX10 as a possible therapeutic target for bone
      destructing disease. J. Cell. Biochem. 118: 4664-4671, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28498636
TI  - Study protocol evaluating the use of bowel stimulation before loop ileostomy
      closure to reduce postoperative ileus: a multicenter randomized controlled trial.
AB  - AIM: Postoperative ileus is the most commonly observed morbidity following
      ileostomy closure. Studies have demonstrated that the defunctionalized bowel of a
      loop ileostomy undergoes a series of functional and structural changes, such as
      atrophy of the intestinal villi and muscular layers, which may contribute to
      ileus. A single-centre study in Spain demonstrated that preoperative bowel
      stimulation via the distal limb of the loop ileostomy decreased postoperative
      ileus, length of stay and time to gastrointestinal function. METHOD: A
      multicentre randomized controlled trial involving patients from Canadian
      institutions was designed to evaluate the effect of preoperative bowel
      stimulation before ileostomy closure on postoperative ileus. Stimulation will
      include canalizing the distal limb of the ileostomy loop with an 18Fr Foley
      catheter and infusing it with a solution of 500 ml of normal saline mixed with 30
      g of a thickening agent (Nestle(c) Thicken-Up(c) ). This will be performed 10
      times over the 3 weeks before ileostomy closure in an outpatient clinic setting
      by a trained Enterostomal Therapy nurse. Surgeons and the treating surgical team
      will be blinded to their patient's group allocation. Data regarding patient
      demographics, and operative and postoperative variables, will be collected
      prospectively. Primary outcome will be postoperative ileus, defined as an
      intolerance to oral food in the absence of clinical or radiological signs of
      obstruction, that either requires nasogastric tube insertion or is associated
      with two of the following on or after post-operative day 3: nausea/vomiting;
      abdominal distension; and the absence of flatus. Secondary outcomes will include
      length of stay, time to tolerating a regular diet, time to first passage of
      flatus or stool and overall morbidity. A cost analysis will be performed to
      compare the costs of conventional care with conventional care plus preoperative
      stimulation. DISCUSSION: This manuscript discusses the potential benefits of
      preoperative bowel stimulation in improving postoperative outcomes and outlines
      our protocol for the first multicenter study to evaluate preoperative bowel
      stimulation before ileostomy closure. The results of this study could have
      considerable implications for the care of patients undergoing ileostomy closure.

PMID- 28498637
TI  - beta2-AR activation induces chemoresistance by modulating p53 acetylation through
      upregulating Sirt1 in cervical cancer cells.
AB  - It has been suggested that beta2-adrenergic receptor (beta2-AR)-mediated
      signaling induced by catecholamines regulates the degradation of p53. However,
      the underlying molecular mechanisms were not known. In the present study, we
      demonstrated that catecholamines upregulated the expression of silent information
      regulator 1 (Sirt1) through activating beta2-AR-mediated signaling pathway, since
      selective beta2-AR antagonist ICI 118, 551 and non-selective beta-blocker
      proprenolol effectively repressed isoproterenol (ISO)-induced Sirt1 expression.
      Catecholamines inhibited doxorubicin (DOX)-induced p53 acetylation and
      transcription-activation activities by inducing the expression of Sirt1.
      Knockdown of the Sirt1 expression by the specific siRNA remarkably blocked the
      inhibitory effects of ISO on DOX-induced p53 acetylation. In addition, we
      demonstrated that catecholamines induced resistance of cervical cancer cells to
      chemotherapeutics both in vitro and in vivo and that beta2-AR was overexpressed
      in cervical cancer tissues. Our data suggest that the p53-dependent,
      chemotherapeutics-induced cytotoxicity in cervical cancer cells may be
      compromised by catecholamines-induced upregulation of the Sirt1 expression
      through activating the beta2-AR signaling.

PMID- 28498638
TI  - Assessing the Influence of Mutation on GTPase Transition States by Using X-ray
      Crystallography, 19 F NMR, and DFT Approaches.
AB  - We report X-ray crystallographic and 19 F NMR studies of the G-protein RhoA
      complexed with MgF3- , GDP, and RhoGAP, which has the mutation Arg85'Ala. When
      combined with DFT calculations, these data permit the identification of changes
      in transition state (TS) properties. The X-ray data show how Tyr34 maintains
      solvent exclusion and the core H-bond network in the active site by relocating to
      replace the missing Arg85' sidechain. The 19 F NMR data show deshielding effects
      that indicate the main function of Arg85' is electronic polarization of the
      transferring phosphoryl group, primarily mediated by H-bonding to O3G and thence
      to PG . DFT calculations identify electron-density redistribution and pinpoint
      why the TS for guanosine 5'-triphosphate (GTP) hydrolysis is higher in energy
      when RhoA is complexed with RhoGAPArg85'Ala relative to wild-type (WT) RhoGAP.
      This study demonstrates that 19 F NMR measurements, in combination with X-ray
      crystallography and DFT calculations, can reliably dissect the response of small
      GTPases to site-specific modifications.

PMID- 28498639
TI  - Three-year risk of high-grade CIN for women aged 30 years or older who undergo
      baseline Pap cytology and HPV co-screening.
AB  - BACKGROUND: Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV)
      DNA cotesting for women aged >=30 years are recommended for the prevention of
      cervical cancer. The objective of the current study was to evaluate the efficacy
      of this cotesting for predicting the risk of high-grade cervical intraepithelial
      neoplasia 3 (CIN3) during a 3-year follow-up period. METHODS: A retrospective
      database search identified women aged >=30 years who had baseline HPV and Pap
      cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results
      were available. The cumulative 3-year risks of developing CIN-3 were calculated.
      RESULTS: The 3-year follow-up data after baseline Pap/HPV cotesting were
      available for 1986 women (mean age, 53 years). Of the 1668 women who had a
      baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up
      Pap cytology result that was negative for intraepithelial lesions or malignancy.
      Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap
      /HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be
      highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result
      (12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P =
      .0032) or a Pap-/HPV- result (0.06%; P<.0001). The 3-year cumulative risk of CIN
      3 was found to be significantly greater for women with an HPV+ result (4.8%)
      compared with those with an HPV- result (0.06%; P<.0001). CONCLUSIONS: Pap
      cytology and HPV cotesting are valuable for stratifying CIN-3 risk. Pap cytology
      and HPV co-screening at a 3-year screening interval appears to carry a low risk
      of CIN-3 for women who have a baseline Pap-/HPV- cotesting result. Cancer
      Cytopathol 2017;125:644-51. (c) 2017 American Cancer Society.

PMID- 28498640
TI  - Recent Advances in Synthetic alpha-Glucosidase Inhibitors.
AB  - Over the past few years, the number of people diagnosed with type 2 diabetes has
      increased owing to an unhealthy diet, a limited amount of exercise, and obesity.
      The search for novel and efficient antidiabetes agents has become an urgent task
      for scientists. Among the antidiabetes drugs, alpha-glucosidase inhibitor drugs
      have been proven to have many advantages over other drugs, and therefore, a large
      number of new compounds as alpha-glucosidase inhibitors has recently been
      reported. In this review, we summarize these newly found alpha-glucosidase
      inhibitors and their structure-activity relationships in antidiabetic studies and
      provide better structures for alpha-glucosidase inhibitors or even preclinical
      candidates. Beyond that, some enlightening strategies for the synthesis of
      relevant compounds are highlighted.

PMID- 28498641
TI  - Quaternary ammonium salts substituted by 5-phenyl-1,3,4-oxadiazole-2-thiol as
      novel antibacterial agents with low cytotoxicity.
AB  - Twenty-one novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) substituted N
      hydroxyethyl quaternary ammonium salts (6a-g, 7a-g, 8a-g) were prepared and
      characterized by FTIR, NMR, and elemental analysis. Compounds 6a, 6c, and 8a were
      confirmed by X-ray single-crystal diffraction. They display the unsurpassed
      antibacterial activity against Staphylococcus aureus, alpha-H-tococcus,
      Escherichia coli, P. aeruginosa, Proteus vulgaris, Canidia Albicans, especially
      6g, 7g, 8g with dodecyl group. Compounds 8a-d with N,N-dihydroxyethyl and POT
      groups display unsurpassed antibacterial activity and non-toxicity. The structure
      activity relationships indicate that POT and flexible dihydroxyethyl group in QAS
      are necessary for antibacterial activity and cytotoxicity. SEM and TEM images of
      E. coli morphologies of 8d show the antibacterial agents can adhere to membrane
      surfaces to inhibit bacterial growth by disrupting peptidoglycan formation and
      releasing bacterial cytoplasm from cell membranes.

PMID- 28498642
TI  - In Situ Probing of Ion Ordering at an Electrified Ionic Liquid/Au Interface.
AB  - Charge transport at the interface of electrodes and ionic liquids is critical for
      the use of the latter as electrolytes. A room-temperature ionic liquid, 1-ethyl
      2,3-dimethylimidazolium bis(trifluoromethanesulfonyl)imide (EMMIM TFSI), is
      investigated in situ under applied bias voltage with a novel method using low
      energy electron and photoemission electron microscopy. Changes in photoelectron
      yield as a function of bias applied to electrodes provide a direct measure of the
      dynamics of ion reconfiguration and electrostatic responses of the EMMIM TFSI.
      Long-range and correlated ionic reconfigurations that occur near the electrodes
      are found to be a function of temperature and thickness, which, in turn, relate
      to ionic mobility and different configurations for out-of-plane ordering near the
      electrode interfaces, with a critical transition in ion mobility for films
      thicker than three monolayers.

PMID- 28498643
TI  - Esophageal dilation in head and neck cancer patients: A systematic review and
      meta-analysis.
AB  - OBJECTIVE: To characterize the safety profile and effectiveness of esophageal
      dilation in head and neck cancer patients. METHODS: A systematic review was
      undertaken for articles reporting outcomes of esophageal dilation in head and
      neck cancer patients. The Medline, Scopus, Web of Science, and Cochrane databases
      were searched in accordance with Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines. Complications related to esophageal dilation in
      head and neck cancer patients was the primary outcome of interest. Success rates,
      demographic data, cancer staging, and treatment data were assessed secondarily.
      Statistical analyses included both qualitative and quantitative assessments. A
      limited meta-analysis and pooling of the data was performed using a random
      effects model. RESULTS: Of the collective 8,243 initial candidate articles, 15
      retrospective studies containing data for a collective 449 patients were
      ultimately included in the analysis. There was significant heterogeneity in the
      outcomes data. With an overall complication rate of 10.6% (95% confidence
      interval [CI]: 4.1%,17%) and a pooled success rate of 72.9% (95% CI: 65.7%,80.1%)
      per patient, the articles generally supported the use of dilation. CONCLUSION:
      Head and neck cancer patients experience a higher rate of complications following
      dilation compared to patients with other causes of benign stricture. Esophageal
      dilation is effective in improving dysphagia, but these benefits are often
      transient and thus necessitate repeat interventions. Laryngoscope, 128:111-117,
      2018.

PMID- 28498644
TI  - Early versus late percutaneous revascularization in patients hospitalized with
      non ST-segment elevation myocardial infarction: The atherosclerosis risk in
      communities surveillance study.
AB  - BACKGROUND: Current guidelines recommend early invasive intervention (<24 hr) for
      high risk patients with non-ST-segment elevation myocardial infarction (NSTEMI).
      A delayed invasive strategy (24-72 hr) is considered reasonable for low risk
      patients. The real-world effectiveness of this strategy is unknown. METHODS: The
      ARIC Study has conducted hospital surveillance of acute myocardial infarction
      (MI) since 1987. NSTEMI was classified using a validated algorithm. We limited
      our study to patients undergoing early (<24 hr of the event onset), or late (>=24
      hr) percutaneous coronary intervention (PCI). Patients were stratified into low
      (TIMI score 2-4), and high risk (TIMI score 5-7, or presence of cardiogenic
      shock, ventricular fibrillation, or cardiac arrest). Associations between early
      versus late PCI and mortality were analyzed using multivariable logistic
      regression adjusted for demographics, hospitalization year, TIMI score, and
      comorbidities. RESULTS: From 1987 to 2012, 6,746 patients were hospitalized with
      NSTEMI and underwent PCI. Most were white (79%), male (68%), with mean age 61
      years. The 28-day and 1-year mortality were 2% and 5%, respectively. Most
      revascularizations (65%) were late. After accounting for potential confounders,
      early PCI was associated with a 58% reduced 28-day mortality (OR = 0.42; 95% CI:
      0.21-0.84) for the entire population, and 57% reduced mortality (OR = 0.43; 95%
      CI: 0.21-0.88) for high risk patients. By 1-year of follow up, there was no
      significant difference in mortality with respect to early vs. late PCI.
      CONCLUSION: In hospitalized NSTEMI patients with high risk of clinical events,
      early PCI is associated with improved 28-day survival.

PMID- 28498645
TI  - Licochalcone A Suppresses Specificity Protein 1 as a Novel Target in Human Breast
      Cancer Cells.
AB  - Licochalcone A (LCA), isolated from the root of Glycyrrhiza inflata, are known to
      have medicinal effect such as anti-oxidant, anti-bacterial, anti-viral, and anti
      cancer. Though, as a pharmacological mechanism regulator, anti-cancer studies on
      LCA were not investigated in human breast cancer. We investigated the anti
      proliferative and apoptotic effect of LCA in human breast cancer cells MCF-7 and
      MDA-MB-231 through MTS assay, PI staining, Annexin-V/7-AAD assay, mitochondrial
      membrane potential assay, multi-caspase assay, RT-PCR, Western blot analysis, and
      anchorage-independent cell transformation assay. Our results showed the little
      difference between two cells, as MCF-7 cell is both estrogen/progesterone
      receptor positive, there were only effect on Sp1 protein level, but not in mRNA
      level. Adversely, estrogen/progesterone/human epidermal growth factor receptor 2
      triple negative, MDA-MB-231 showed decreased Sp1 mRNA, and protein levels. To
      confirm the participation of Sp1 in breast cancer cell viability, siRNA
      techniques were introduced. Both cells showed dysfunction of mitochondrial
      membrane potential and mitochondrial ROS production, which reflects it passed
      intracellular mitochondrial apoptosis pathway. Additionally, LCA showed the anti
      proliferative and apoptotic effect in breast cancer cells through regulating Sp1
      and apoptosis-related proteins in a dose- and a time-dependent manner.
      Consequently, LCA might be a potential anti-breast cancer drug substitute. J.
      Cell. Biochem. 118: 4652-4663, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28498646
TI  - Cook Cervical Ripening Balloon successfully prevents excessive hemorrhage
      combined with ultrasound-guided suction curettage in the treatment of cesarean
      scar pregnancy.
AB  - AIM: Cesarean scar pregnancy (CSP) is a rare occurrence of ectopic pregnancy. CSP
      incidence has increased significantly as a result of the increase in cesarean
      section rates. At present, there are no standard treatment guidelines for CSP;
      therefore, we report a minimally invasive treatment method for patients diagnosed
      with CSP. METHODS: This study included 15 women who were diagnosed with CSP.
      Ultrasound-guided suction curettage was performed on all patients. The Cook
      Cervical Ripening Balloon was used to tamponade and prevent hemorrhage during the
      procedure. In 12 patients, the balloon was placed immediately following
      ultrasound-guided suction curettage; in two patients, the balloon was placed when
      excessive bleeding occurred post-curettage; and in one patient, the balloon was
      placed after the gestational sac evacuated by itself, and then suction aspiration
      was performed on day 5, following the evacuation. Human chorionic gonadotropin
      levels were evaluated three days after the procedure. RESULTS: Placement and
      inflation of the Cook Cervical Ripening Balloon was well tolerated by all
      patients. The balloon tamponade effectively reduced or prevented vaginal bleeding
      in all patients, and none of the patients had an estimated blood loss higher than
      1000 ml. CONCLUSIONS: Ultrasound-guided suction curettage is effective in the
      treatment of CSP. The Cook Cervical Ripening Balloon is easy to place and inflate
      and successfully prevented bleeding or assisted in the management of bleeding
      complications. We recommend the Cook Cervical Ripening Balloon as an adjuvant
      method for ultrasound-guided suction curettage for the treatment of CSP.

PMID- 28498647
TI  - Association Between Staphylococcus aureus Bacteremia and Hospital Mortality in
      Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From
      Japanese Tertiary Care Centers.
AB  - Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been
      a major cause of death in hemodialysis patients. We examined whether SAB is a
      risk for mortality among chronic hemodialysis patients in Japan where the
      standard vascular access is arteriovenous fistula (AVF). This was a multicenter,
      retrospective study of maintenance hemodialysis patients with bloodstream
      infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint
      was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA)
      and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB
      cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly
      associated with hospital mortality after adjustment for potential confounders,
      including type of vascular access (OR 3.26). S. aureus was the leading cause of
      BSI and hospital mortality among this cohort. Therefore, initial empiric
      treatment should cover for S. aureus.

PMID- 28498648
TI  - Extension of Pharmacy Copayments for Medications. Resolution of interim final
      rule.
AB  - The Department of Veterans Affairs (VA) notifies the public that an interim final
      rule freezing medication copayments for veterans in priority groups 2 through 8,
      published on December 7, 2016, was superseded by a final rule amending its
      regulations concerning copayments that published on December 12, 2016. The
      interim final rule received no public comments.

PMID- 28498649
TI  - Payment or Reimbursement for Certain Medical Expenses for Camp Lejeune Family
      Members. Final rule.
AB  - The Department of Veterans Affairs (VA) adopts as final an interim final rule
      addressing payment or reimbursement of certain medical expenses for family
      members of Camp Lejeune veterans. Under this rule, VA reimburses family members,
      or pays providers, for medical expenses incurred as a result of certain illnesses
      and conditions that may be associated with contaminants present in the base water
      supply at U.S. Marine Corps Base Camp Lejeune (Camp Lejeune), North Carolina,
      from August 1, 1953, to December 31, 1987. Payment or reimbursement is made
      within the limitations set forth in statute and Camp Lejeune family members
      receive hospital care and medical services that are consistent with the manner in
      which we provide hospital care and medical services to Camp Lejeune veterans. The
      statutory authority has since been amended to also include certain veterans'
      family members who resided at Camp Lejeune, North Carolina, for no less than 30
      days (consecutive or nonconsecutive) between August 1, 1953, and December 31,
      1987. This final rule will reflect that statutory change and will address public
      comments received in response to the interim final rule.

PMID- 28498650
TI  - Medicare Beneficiaries' High Out-of-Pocket Costs: Cost Burdens by Income and
      Health Status.
AB  - ISSUE: Fifty-six million people--17 percent of the U.S. population--rely on
      Medicare. Yet, its benefits exclude dental, vision, hearing, and long-term
      services, and it contains no ceiling on out-of-pocket costs for covered services,
      exposing beneficiaries to high costs. GOAL: To inform discussion of possible
      changes to Medicare, this issue brief looks at beneficiaries' out-of-pocket costs
      by income and health status. METHODS: Spending estimates based on the Medicare
      Current Beneficiary Survey.FINDINGS AND CONCLUSION: More than one-fourth of all
      Medicare beneficiaries--15 million people--spend 20 percent or more of their
      incomes on premiums plus medical care, including cost-sharing and uncovered
      services. Beneficiaries with incomes below 200 percent of the poverty level (just
      under $24,000 for a single person) and those with multiple chronic conditions or
      functional limitations are at significant financial risk. Overall, beneficiaries
      spent an average of $3,024 per year on out-of-pocket costs. Financial burdens and
      access gaps highlight the need to approach reform with caution. Already-high
      burdens suggest restructuring cost-sharing to ensure affordability and to provide
      relief for low-income beneficiaries.

PMID- 28498652
TI  - Mechanically-Controlled Reversible Spin Crossover of Single Fe-Porphyrin
      Molecules.
AB  - Spin-crossover (SCO) molecules are thought to be ideal systems for molecular
      spintronics when SCO can be precisely controlled at the single-molecule level.
      This is demonstrated here in the single-molecule junctions of Fe-porphyrin formed
      in a scanning tunneling microscope. Experimentally, we find that the junctions
      feature a zero-bias resonance in molecular conductance associated with the Fe
      spin center. When mechanically stretching or squeezing the junctions by adjusting
      the tip height, the line shape of the zero-bias resonance varies reversibly.
      First-principles calculations reveal that widening the junction gap by 2 A
      transforms the macrocyclic core hosting the Fe center from a saddle to a planar
      conformation. This conformational change shortens the Fe-N bonds by 3%, which
      changes the Fe spin state from S = 2 to S = 1.

PMID- 28498651
TI  - Design of Benzoxathiazin-3-one 1,1-Dioxides as a New Class of Irreversible Serine
      Hydrolase Inhibitors: Discovery of a Uniquely Selective PNPLA4 Inhibitor.
AB  - The design and examination of 4,1,2-benzoxathiazin-3-one 1,1-dioxides as
      candidate serine hydrolase inhibitors are disclosed, and represent the synthesis
      and study of a previously unexplored heterocycle. This new class of activated
      cyclic carbamates provided selective irreversible inhibition of a small subset of
      serine hydrolases without release of a leaving group, does not covalently modify
      active site catalytic cysteine and lysine residues of other enzyme classes, and
      was found to be amenable to predictable structural modifications that modulate
      intrinsic reactivity or active site recognition. Even more remarkable and within
      the small pilot series of candidate inhibitors examined in an initial study, an
      exquisitely selective inhibitor for a poorly characterized serine hydrolase
      (PNPLA4, patatin-like phospholipase domain-containing protein 4) involved in
      adipocyte triglyceride homeostasis was discovered.

PMID- 28498653
TI  - Recovering Rare Earth Elements from Aqueous Solution with Porous Amine-Epoxy
      Networks.
AB  - Recovering aqueous rare earth elements (REEs) from domestic water sources is one
      key strategy to diminish the U.S.'s foreign reliance of these precious
      commodities. Herein, we synthesized an array of porous, amine-epoxy monolith and
      particle REE recovery sorbents from different polyamine, namely
      tetraethylenepentamine, and diepoxide (E2), triepoxide (E3), and tetra-epoxide
      (E4) monomer combinations via a polymer-induced phase separation (PIPS) method.
      The polyamines provided -NH2 (primary amine) plus -NH (secondary amine) REE
      adsorption sites, which were partially reacted with C-O-C (epoxide) groups at
      different amine/epoxide ratios to precipitate porous materials that exhibited a
      wide range of apparent porosities and REE recoveries/affinities. Specifically,
      polymer particles (ground monoliths) were tested for their recovery of La3+,
      Nd3+, Eu3+, Dy3+, and Yb3+ (Ln3+) species from ppm-level, model REE solutions (pH
      ~ 2.4, 5.5, and 6.4) and a ppb-level, simulated acid mine drainage (AMD) solution
      (pH ~ 2.6). Screening the sorbents revealed that E3/TEPA-88 (88% theoretical
      reaction of -NH2 plus -NH) recovered, overall, the highest percentage of Ln3+
      species of all particles from model 100 ppm- and 500 ppm-concentrated REE
      solutions. Water swelling (monoliths) and ex situ, diffuse reflectance infrared
      Fourier transform spectroscopy (DRIFTS) (ground monoliths/particles) data
      revealed the high REE uptake by the optimized particles was facilitated by
      effective distribution of amine and hydroxyl groups within a porous, phase
      separated polymer network. In situ DRIFTS results clarified that phase
      separation, in part, resulted from polymerization of the TEPA-E3 (N-N-diglycidyl
      4-glycidyloxyaniline) species in the porogen via C-N bond formation, especially
      at higher temperatures. Most importantly, the E3/TEPA-88 material cyclically
      recovered >93% of ppb-level Ln3+ species from AMD solution in a recovery-strip
      recovery scheme, highlighting the efficacy of these materials for practical
      applications.

PMID- 28498654
TI  - Template-Mediated Ni(II) Dispersion in Mesoporous SiO2 for Preparation of Highly
      Dispersed Ni Catalysts: Influence of Template Type.
AB  - Supported Ni catalysts on three mesoporous SiO2 supports (i.e., SBA-15, MCM-41,
      and HMS) were prepared using a solid-state reaction between Ni(NO3)2 and organic
      template-occluded mesoporous SiO2. For comparison, supported Ni catalysts on
      mesoporous SiO2 synthesized by the conventional impregnation method were also
      included. The catalysts were characterized by scanning electron microscopy, X-ray
      diffraction, UV-vis diffuse reflectance spectroscopy, N2 adsorption, X-ray
      photoelectron spectroscopy, H2 temperature-programmed reduction, transmission
      electron microscopy, and transmission electron microscopy-energy-dispersive X
      ray. The catalytic properties of the catalysts were evaluated using gas-phase
      catalytic hydrodechlorination of 1,2-dichloroethane. The results showed that upon
      grinding Ni(NO3)2 with template-occluded mesoporous SiO2, strong coordination
      between Ni2+ and dodecylamine was identified in the Ni(NO3)2-HMS system.
      Additionally, the results of H2 temperature-programmed reduction revealed that
      NiO in calcined NiO/HMS was reduced at higher temperature than those in calcined
      NiO/SBA-15 and NiO/MCM-41, reflecting the presence of a strong interaction
      between NiO and mesoporous SiO2 in NiO/HMS. Consistently, the average particle
      sizes of metallic Ni were found to be 2.7, 3.4, and 9.6 nm in H2-reduced Ni/HMS,
      Ni/SBA-15, and Ni/MCM-41, respectively, indicative of a much higher Ni dispersion
      in Ni/HMS. For the catalytic hydrodechlorination of 1,2-dichloroethane, Ni/MCM-41
      synthesized by the solid-state reaction method exhibited a catalytic activity
      similar to that prepared by the impregnation method, while higher catalytic
      activities were observed on Ni/HMS and Ni/SBA-15 than on their counterparts
      prepared by the impregnation method. Furthermore, a higher conversion was
      identified on Ni/HMS than on Ni/SBA-15 and Ni/MCM-41, highlighting the importance
      of template type for the preparation of highly dispersed metal catalysts on
      mesoporous SiO2.

PMID- 28498655
TI  - Discovery of an Orally Bioavailable Benzimidazole Diacylglycerol Acyltransferase
      1 (DGAT1) Inhibitor That Suppresses Body Weight Gain in Diet-Induced Obese Dogs
      and Postprandial Triglycerides in Humans.
AB  - Modification of a gut restricted class of benzimidazole DGAT1 inhibitor 1 led to
      9 with good oral bioavailability. The key structural changes to 1 include
      bioisosteric replacement of the amide with oxadiazole and alpha,alpha
      dimethylation of the carboxylic acid, improving DGAT1 potency and gut
      permeability. Since DGAT1 is expressed in the small intestine, both 1 and 9 can
      suppress postprandial triglycerides during acute oral lipid challenges in rats
      and dogs. Interestingly, only 9 was found to be effective in suppressing body
      weight gain relative to control in a diet-induced obese dog model, suggesting the
      importance of systemic inhibition of DGAT1 for body weight control. 9 has
      advanced to clinical investigation and successfully suppressed postprandial
      triglycerides during an acute meal challenge in humans.

PMID- 28498656
TI  - Occupational Exposure to Polycyclic Aromatic Hydrocarbon of Wildland Firefighters
      at Prescribed and Wildland Fires.
AB  - Wildland firefighters suppressing wildland fires or conducting prescribed fires
      work long shifts during which they are exposed to high levels of wood smoke with
      no respiratory protection. Polycyclic aromatic hydrocarbons (PAHs) are hazardous
      air pollutants formed during incomplete combustion. Exposure to PAHs was measured
      for 21 wildland firefighters suppressing two wildland fires and 4 wildland
      firefighters conducting prescribed burns in California. Personal air samples were
      actively collected using XAD4-coated quartz fiber filters and XAD2 sorbent tubes.
      Samples were analyzed for 17 individual PAHs through extraction with
      dichloromethane and gas chromatograph-mass spectrometer analysis. Naphthalene,
      retene, and phenanthrene were consistently the highest measured PAHs. PAH
      concentrations were higher at wildland fires compared to prescribed fires and
      were highest for firefighters during job tasks that involve the most direct
      contact with smoke near an actively burning wildland fire. Although
      concentrations did not exceed current occupational exposure limits, wildland
      firefighters are exposed to PAHs not only on the fire line at wildland fires, but
      also while working prescribed burns and while off-duty. Characterization of
      occupational exposures from wildland firefighting is important to understand
      better any potential long-term health effects.

PMID- 28498657
TI  - Surface-Enhanced Raman Spectroscopy: A Facile and Rapid Method for the Chemical
      Component Study of Individual Atmospheric Aerosol.
AB  - A simple and rapid method for detecting chemical components of individual aerosol
      particles on Klarite substrate with surface-enhanced Raman spectroscopy (SERS) is
      described. For both single simulated aerosol particles and ambient atmospheric
      particles, this new analytical method promotes the enhancement factor of the
      Raman signal. The spectra of ammonium sulfate and naphthalene particles at the
      microscopic level are enhanced by a factor of 6 and therefore greatly improve the
      detection of the chemical composition of an individual aerosol particle. When
      aerosol particles are found over a microscopic domain, a set of Raman spectra
      with chemical information can be obtained via SERS mapping. The maps illustrate
      the distribution of organic or inorganic species on the SERS substrate. This
      constitutes a facile and rapid method to study aerosol particles. This new method
      allows the analysis of chemical composition in single aerosol particles,
      demonstrating the power of SERS to probe the ambient atmospheric particles and to
      study the formation of aerosol particles.

PMID- 28498659
TI  - Modeling the Onset of Phase Separation in CaO-SiO2-CaCl2 Chlorine-Containing
      Silicate Glasses.
AB  - The addition of chlorine into a bioactive glass composition is expected to reduce
      its abrasiveness and increase its bioactivity, which is important for dental
      applications such as toothpastes. There is a lack of information and
      understanding regarding the structural role of chlorine in chlorine-containing
      bioactive silicate glasses. This has prompted classical core-shell model
      molecular dynamics simulations of (50 - x/2)CaO-(50 - x/2)SiO2-xCaCl2 glasses to
      be performed, where x ranges from x = 0.0 to 43.1 mol % CaCl2. These ternary
      glasses are advantageous for a fundamental study because they do not have
      additional network formers (e.g., phosphorus pentoxide) or modifiers (e.g.,
      sodium) typically found in bioactive glass compositions. The (50 - x/2)CaO-(50 -
      x/2)SiO2-xCaCl2 glasses were seen to become phase-separated around the x = 16.1
      mol % CaCl2 composition, and chlorine predominantly coordinated with calcium.
      These findings provide a solid foundation for further computational modeling work
      on more complex chlorine-containing bioactive glass compositions.

PMID- 28498658
TI  - Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2
      yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent,
      Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by
      Fragment-Based Drug Design.
AB  - Through fragment-based drug design focused on engaging the active site of IRAK4
      and leveraging three-dimensional topology in a ligand-efficient manner, a
      micromolar hit identified from a screen of a Pfizer fragment library was
      optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays.
      The medicinal chemistry effort featured the judicious placement of lipophilicity,
      informed by co-crystal structures with IRAK4 and optimization of ADME properties
      to deliver clinical candidate PF-06650833 (compound 40). This compound displays a
      5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase
      selectivity, and pharmacokinetic properties suitable for oral administration.

PMID- 28498660
TI  - Self-Assembled Ruthenium(II)Porphyrin-Aluminium(III)Porphyrin-Fullerene Triad for
      Long-Lived Photoinduced Charge Separation.
AB  - A very efficient metal-mediated strategy led, in a single step, to a quantitative
      construction of a new three-component multichromophoric system containing one
      fullerene monoadduct, one aluminium(III) monopyridylporphyrin, and one
      ruthenium(II) tetraphenylporphyrin. The Al(III) monopyridylporphyrin component
      plays the pivotal role in directing the correct self-assembly process and behaves
      as the antenna unit for the photoinduced processes of interest. A detailed study
      of the photophysical behavior of the triad was carried out in different solvents
      (CH2Cl2, THF, and toluene) by stationary and time-resolved emission and
      absorption spectroscopy in the pico- and nanosecond time domains. Following
      excitation of the Al-porphyrin, the strong fluorescence typical of this unit was
      strongly quenched. The time-resolved absorption experiments provided evidence for
      the occurrence of stepwise photoinduced electron and hole transfer processes,
      leading to a charge-separated state with reduced fullerene acceptor and oxidized
      ruthenium porphyrin donor. The time constant values measured in CH2Cl2 for the
      formation of charge-separated state Ru-Al+-C60- (10 ps), the charge shift process
      (Ru-Al+-C60- -> Ru+-Al-C60-), where a hole is transferred from Al-based to Ru
      based unit (75 ps), and the charge recombination process to ground state (>5 ns),
      can be rationalized within the Marcus theory. Although the charge-separating
      performance of this triad is not outstanding, this study demonstrates that, using
      the self-assembling strategy, improvements can be obtained by appropriate
      chemical modifications of the individual molecular components.

PMID- 28498661
TI  - Mesoporous Silica Nanoparticles-Encapsulated Agarose and Heparin as Anticoagulant
      and Resisting Bacterial Adhesion Coating for Biomedical Silicone.
AB  - Silicone catheter has been widely used in peritoneal dialysis. The research
      missions of improving blood compatibility and the ability of resisting bacterial
      adhesion of silicone catheter have been implemented for the biomedical
      requirements. However, most of modification methods of surface modification were
      only able to develop the blood-contacting biomaterials with good
      hemocompatibility. It is difficult for the biomaterials to resist bacterial
      adhesion. Here, agarose was selected to resist bacterial adhesion, and heparin
      was chosen to improve hemocompatibility of materials. Both of them were loaded
      into mesoporous silica nanoparticles (MSNs), which were successfully modified on
      the silicone film surface via electrostatic interaction. Structures of the
      mesoporous coatings were characterized in detail by dynamic light scattering,
      transmission electron microscopy, Brunauer-Emmett-Teller surface area,
      thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning
      electron microscope, and water contact angle. Platelet adhesion and aggregation,
      whole blood contact test, hemolysis and related morphology test of red blood
      cells, in vitro clotting time tests, and bacterial adhesion assay were performed
      to evaluate the anticoagulant effect and the ability of resisting bacterial
      adhesion of the modified silicone films. Results indicated that silicone films
      modified by MSNs had a good anticoagulant effect and could resist bacterial
      adhesion. The modified silicone films have potential as blood-contacting
      biomaterials that were attributed to their biomedical properties.

PMID- 28498662
TI  - Submolecular Gates Self-Assemble for Hot-Electron Transfer in Proteins.
AB  - Redox reactions play key roles in fundamental biological processes. The related
      spatial organization of donors and acceptors is assumed to undergo evolutionary
      optimization facilitating charge mobilization within the relevant biological
      context. Experimental information from submolecular functional sites is needed to
      understand the organization strategies and driving forces involved in the self
      development of structure-function relationships. Here we exploit chemically
      resolved electrical measurements (CREM) to probe the atom-specific electrostatic
      potentials (ESPs) in artificial arrays of bacteriochlorophyll (BChl) derivatives
      that provide model systems for photoexcited (hot) electron donation and
      withdrawal. On the basis of computations we show that native BChl's in the
      photosynthetic reaction center (RC) self-assemble at their ground-state as
      aligned gates for functional charge transfer. The combined computational and
      experimental results further reveal how site-specific polarizability
      perpendicular to the molecular plane enhances the hot-electron transport. Maximal
      transport efficiency is predicted for a specific, ~5 A, distance above the center
      of the metalized BChl, which is in remarkably close agreement with the distance
      and mutual orientation of corresponding native cofactors. These findings provide
      new metrics and guidelines for analysis of biological redox centers and for
      designing charge mobilizing machines such as artificial photosynthesis.

PMID- 28498664
TI  - Atmospheric Aqueous Aerosol Surface Tensions: Isotherm-Based Modeling and
      Biphasic Microfluidic Measurements.
AB  - Surface properties of atmospheric aerosol particles are crucial for accurate
      assessments of the fates of liquid particles in the atmosphere. Surface tension
      directly influences predictions of particle activation to clouds, as well as
      indirectly acting as a proxy for chemical surface partitioning. Challenges to
      accounting for surface effects arise from surface tension dependence on solution
      concentration and the presence of complex aqueous mixtures in aerosols, including
      both surface-active organic solutes and inorganic electrolytes. Also, the
      interface itself is varied, in that it may be a liquid-vapor interface, as in the
      surface of an aerosol particle with ambient air, or a liquid-liquid interface
      between two immiscible liquids, as in the interior surfaces that exist in
      multiphase particles. In this Feature Article, we highlight our previous work
      entailing thermodynamic modeling of liquid-vapor surfaces to predict surface
      tension and microscopic examinations of liquid-liquid interfacial phenomena to
      measure interfacial tension using biphasic microscale flows. New results are
      presented for binary aqueous organic acids and their ternary solutions with
      ammonium sulfate. Ultimately, improved understanding of aerosol particle surfaces
      would enhance treatment of aerosol particle-to-cloud activation states and
      aerosol effects on climate.

PMID- 28498663
TI  - Development of a Multiphysics Model to Characterize the Responsive Behavior of
      Magnetic-Sensitive Hydrogels with Finite Deformation.
AB  - A novel multiphysics model is developed in this paper for simulation of the
      responsive behavior of the magnetic-sensitive hydrogel, with the effects of
      magneto-chemo-mechanical coupled fields, which is termed the multi-effect
      coupling magnetic-stimulus (MECm) model. In this work, the magnetic
      susceptibility for magnetization of the general magnetic hydrogel is defined as a
      function of finite deformation, instead of a constant for an ideal magnetic
      hydrogel. The present constitutive equations, formulated by the second law of
      thermodynamics, account for the effects of the chemical potential, the externally
      applied magnetic field, and the finite deformation. In particular, a novel free
      energy density is proposed with consideration of the magnetic effect associated
      with finite deformation, instead of volume fraction. After examination with
      published experimental data, it is confirmed that the MECm model can well capture
      the responsive behavior of the magnetic hydrogel, including the deformation and
      its instability and hysteresis under a uniform or nonuniform magnetic field. The
      parameter studies are then carried out for influences of the magnetic and
      geometric properties, including the magnetic intensity, shear modulus, and volume
      fraction of the magnetic particles, on the behavior of the magnetic hydrogel, for
      a deeper insight into the fundamental mechanism of the magnetic hydrogels.

PMID- 28498665
TI  - Iron Phosphate Catalyzed Asymmetric Cross-Dehydrogenative Coupling of 2-Naphthols
      with beta-Ketoesters.
AB  - Chiral iron phosphate complexes were successfully exploited for asymmetric cross
      dehydrogenative coupling reactions between 2-naphthols and beta-ketoester
      derivatives. On the basis of kinetic studies, it is suggested that iron
      monophosphate complexes constitute the active catalysts that induce
      stereoselectivity during the carbon-carbon bond-formation step.

PMID- 28498666
TI  - Full-Dimensional Theory of Pair-Correlated HNCO Photofragmentation.
AB  - Full-dimensional semiclassical dynamical calculations combining classical paths
      and Bohr quantization of product internal motions are reported for the prototype
      photofragmentation of isocyanic acid in the S1 state. These calculations allow
      one to closely reproduce for the first time key features of state-of-the-art
      imaging measurements at photolysis wavelengths of 201 and 210 nm while providing
      insight into the underlying dissociation mechanism. Quantum scattering
      calculations being beyond reach for most polyatomic fissions, pair-correlated
      data on these processes are much more often measured than predicted. Our
      theoretical approach can be used to fill this gap.

PMID- 28498667
TI  - Oxidative Addition Complexes as Precatalysts for Cross-Coupling Reactions
      Requiring Extremely Bulky Biarylphosphine Ligands.
AB  - In this report, we describe the application of palladium-based oxidative addition
      complexes (OACs) as effective precatalysts for C-N, C-O, and C-F cross-coupling
      reactions with a variety of (hetero)arenes. These complexes offer a convenient
      alternative to previously developed classes of precatalysts, particularly in the
      case of the bulkiest biarylphosphine ligands, for which palladacycle-based
      precatalysts do not readily form. The precatalysts described herein are easily
      prepared and stable to long-term storage under air.

PMID- 28498668
TI  - Kinetics of the Reactions of NO3 Radical with Methacrylate Esters.
AB  - Two different experimental methods (relative rate and absolute rate methods) were
      used to measure the rate coefficients for the reactions of NO3 radical with six
      methacrylate esters: methyl methacrylate (MMA, k1), ethyl methacrylate (EMA, k2),
      propyl methacrylate (PMA, k3), isopropyl methacrylate (IPMA, k4), butyl
      methacrylate (BMA, k5), and isobutyl methacrylate (IBMA, k6). In the relative
      rate method, the loss of the esters relative to that of a reference compound was
      followed in a 7300 L Teflon-walled chamber at 298 +/- 2 K and 1000 +/- 5 hpa. In
      the absolute method, the temporal profiles of NO3 and N2O5 were followed by using
      a dual channel cavity ring-down spectrometer in the presence of an excess of
      ester in the 7300 L chamber. The rate coefficients from these two methods
      (weighted averages) in the units of 10-15 cm3 molecule-1 s-1 at 298 K are k1 =
      2.98 +/- 0.35, k2 = 4.67 +/- 0.49, k3 = 5.23 +/- 0.60, k4 = 7.91 +/- 1.00, k5 =
      5.91 +/- 0.58, and k6 = 6.24 +/- 0.66. The quoted uncertainties are at the 2sigma
      level and include estimated systematic errors. Unweighted averages are also
      reported. In addition, the rate coefficient k7 for the reaction of NO3 radical
      with deuterated methyl methacrylate (MMA-d8) was measured by using the relative
      rate method to be essentially the same as k1. The trends in the measured rate
      coefficient with the length and nature of the alkyl group, along with the
      equivalence of k1 and k7, strongly suggest that the reaction of NO3 with the
      methacrylate esters proceeds via addition to the double bond on the methacrylate
      group. The present results are compared with those from previous studies. Using
      the measured values of the rate coefficients, along with those for reactions of
      these esters with OH, O3, and chlorine atoms, we calculated the atmospheric
      lifetimes of methacrylate esters. We suggest that NO3 radicals do contribute to
      the atmospheric loss of these unsaturated esters, but to a lesser extent than
      their reactions with OH and O3.

PMID- 28498669
TI  - Multiscale Model for Electrokinetic Transport in Networks of Pores, Part I: Model
      Derivation.
AB  - We present an efficient and robust numerical model for the simulation of
      electrokinetic phenomena in porous media and microstructure networks considering
      a wide range of applications including energy conversion, deionization, and
      microfluidic-based lab-on-a-chip systems. Coupling between fluid flow and ion
      transport in these networks is governed by the Poisson-Nernst-Planck-Stokes
      equations. These equations describe a wide range of phenomena that can interact
      in a complex fashion when coupled in networks involving multiple pores with
      variable properties. Capturing these phenomena by direct simulation of the
      governing equations in multidimensions is prohibitively expensive. We present
      here a reduced-order model that treats a network of many pores via solutions to
      1D equations. Assuming that each pore in the network is long and thin, we derive
      a 1D model describing the transport in the pore's longitudinal direction. We take
      into account the cross-sectional nonuniformity of potential and ion concentration
      fields in the form of area-averaged coefficients in different flux terms
      representing fluid flow, electric current, and ion fluxes. These coefficients are
      obtained from the solutions to the Poisson-Boltzmann equation and are tabulated
      against dimensionless surface charge and dimensionless thickness of the electric
      double layer (EDL). Although similar models have been attempted in the past,
      distinct advantages of the present framework include a fully conservative
      discretization with zero numerical leakage, fully bounded area-averaged
      coefficients without any singularity in the limit of infinitely thick EDLs, a
      flux discretization that exactly preserves equilibrium conditions, and extension
      to a general network of pores with multiple intersections. In part II of this two
      article series, we present a numerical implementation of this model and
      demonstrate its applications in predicting a wide range of electrokinetic
      phenomena in microstructures.

PMID- 28498670
TI  - Palladium-Catalyzed Aminocarbonylation in Solid-Phase Peptide Synthesis: A Method
      for Capping, Cyclization, and Isotope Labeling.
AB  - A new synthetic approach for introducing N-capping groups onto peptides attached
      to a solid support, combining aminocarbonylation under mild conditions using a
      palladacycle precatalyst and solid-phase peptide synthesis, is reported. The use
      of a silacarboxylic acid as an in situ CO-releasing molecule allowed the reaction
      to be performed in a single vial. The method also enables versatile substitution
      of side chains, side-chain-to-side-chain cyclizations, and selective [13C] acyl
      labeling of modified peptides.

PMID- 28498671
TI  - Correction to "Lanesoic Acid: A Cytotoxic Zwitterion from Theonella sp."

PMID- 28498672
TI  - Photovoltaic Hybrid Perovskites under Pressure.
AB  - High-pressure studies on methylammonium trihaloplumbates, of general formula
      [CH3NH3]+PbX3- (abbreviated MAPbX3, where X = Cl, Br, I), and its analogues shed
      new light on the materials for harvesting solar energy and open new perspectives
      for photovoltaic science and technology. However, there are considerable
      discrepancies between the reported structural, calorimetric, and spectroscopic
      results and even between the results obtained by the same technique, for example,
      of X-ray diffraction. The origins of these discrepancies and possible pitfalls in
      the diffraction and spectroscopic studies on MAPbX3 crystals have been
      investigated. Several new effects revealed in this study involve phase
      transitions of exceptionally slow kinetics and the coexistence of phases. They
      strongly affect photovoltaic properties and are essential for theory,
      predictions, and technological applications.

PMID- 28498673
TI  - Single Particle Dynamics at the Intrinsic Surface of Various Apolar, Aprotic
      Dipolar, and Hydrogen Bonding Liquids As Seen from Computer Simulations.
AB  - We investigate the single molecule dynamics at the intrinsic liquid/vapor
      interface of five different molecular liquids (carbon tetrachloride, acetone,
      acetonitrile, methanol, and water). After assessing that the characteristic
      residence times in the surface layer are long enough for a meaningful definition
      of several transport properties within the layer itself, we characterize the
      dynamics of the individual molecules at the liquid surface by analyzing their
      normal and lateral mean-square displacements and lateral velocity autocorrelation
      functions and, in the case of the hydrogen bonding liquids (i.e., water and
      methanol), also the properties of the hydrogen bonds. Further, dynamical
      properties as well as the clustering of the molecules residing unusually long in
      the surface layer are also investigated. The global picture emerging from this
      analysis is that of a noticeably enhanced dynamics of the molecules at the liquid
      surface, with diffusion coefficients up to 4 times larger than in the bulk, and
      the disappearance of the caging effect at the surface of all liquids but water.
      The dynamics of water is dominated by the strong hydrogen bonding structure also
      at the liquid surface.

PMID- 28498674
TI  - Anisotropic Fe3O4/Mn3O4 Hybrid Nanocrystals with Unique Magnetic Properties.
AB  - This work explores novel nanomagnets by site- and facet-selective epitaxy of
      Mn3O4 nanodomains onto colloidal Fe3O4 nanoprisms in solution. At 190  degrees C,
      the Mn3O4 nanodomains epitaxially grow at three vertexes of the Fe3O4 nanoprisms
      in solution and form horns-on-prism hybrid nanocrystals. At 240  degrees C and in
      the same reaction solution, the epitaxy occurs on the top facet of the Fe3O4
      nanoprisms, which results in prism-on-prism hybrid nanocrystals. As the
      temperature increases from 190 to 240  degrees C, the ratio between the prism-on
      prism and horns-on-prism nanocrystals increases. A possible formation mechanism
      of Fe3O4/Mn3O4 hybrid nanocrystals is proposed. Novel magnetic behaviors, such as
      compensation point, large positive (or negative) exchange bias, and unusual
      hysteresis loop character (constricted at low field and expanded at high field),
      have been observed for both types of anisotropic hybrid nanomagnets. These unique
      magnetic properties are consistent with controlled switch of relative
      magnetization orientations between Fe3O4 and Mn3O4 nanodomains from parallel to
      antiparallel exchange-coupled configurations.

PMID- 28498675
TI  - Explicit Solvent Hydration Benchmark for Proteins with Application to the PBSA
      Method.
AB  - Explicit and implicit solvent models have a proven record of delivering hydration
      free energies of small, druglike solutes in reasonable agreement with experiment.
      Hydration of macromolecules, such as proteins, is to a large extent uncharted
      territory, with few results shedding light on quantitative consistency between
      different solvent models, let alone their ability to reproduce real water. In
      this work, based on extensive explicit solvent simulations employing TIP3P and
      SPC/E water models we analyze hydration free energy changes between fixed
      conformations of 5 diverse proteins, including large multidomain structures. For
      the two solvent models we find better agreement in electrostatic rather than
      nonpolar contributions (RMSE of 2.3 and 2.7 kcal/mol, respectively), even though
      absolute values of the latter are typically an order of magnitude smaller. We
      also highlight the importance of finite size corrections to relative protein
      hydration free energies, which turn out to be rather large, on the order of
      several kcal/mol, and are necessary for proper interpretation of results obtained
      under periodic boundary conditions. We further compare gathered data with
      predictions of the implicit solvent approach based on the Poisson equation and
      the surface or volume based nonpolar term. We find definitely lesser consistency
      than between the two explicit models (RMSE between implicit and TIP3 results of
      11.3 and 8.4 kcal/mol for electrostatic and nonpolar contributions,
      respectively). In the process we determine the value of the protein dielectric
      constant and the geometric model for the dielectric boundary that provide for the
      best agreement. Finally, we evaluate the usefulness of surface and volume based
      models of nonpolar contributions to hydration free energy of large biomolecules.

PMID- 28498676
TI  - Intermolecular Interactions in Highly Disordered, Confined Dense N2.
AB  - Molecular nitrogen is a benchmark system for condensed matter and, in particular,
      for looking at universal properties of strongly confined dense systems. We
      conducted Raman and X-ray diffraction measurements on a dense and disordered form
      of molecular nitrogen subnanoconfined in a noncatalytic pure SiO2 zeolite under
      pressure, up to 50 GPa. In this form, N2-N2 interactions and, consequently,
      distances are found to be very close to those of bulk N2 and intramolecular
      interactions progressively weaken upon increasing pressure. Surprisingly, the
      filled zeolite is still crystalline at 50 GPa with silicon in tetrahedral
      coordination by oxygen, which is a record pressure for this type of coordination
      among all the known forms of silica. We have thus found a rationale for the
      polymerization of a number molecules occurring in the microchannels of
      noncatalytic zeolites under pressure, where the pressure threshold is found to be
      very similar to that observed in bulk samples.

PMID- 28498677
TI  - Radical Cation Cyclopropanations via Chromium Photooxidative Catalysis.
AB  - The chromium photocatalyzed cyclopropanation of diazo reagents with electron-rich
      alkenes is described. The transformation occurs under mild conditions and
      features specific distinctions from traditional diazo-based cyclopropanations
      (e.g., avoiding beta-hydride elimination, chemoselectivity considerations, etc.).
      The reaction appears to work most effectively using chromium catalysis, and a
      number of decorated cyclopropanes can be accessed in generally good yields.

PMID- 28498678
TI  - Mechanisms and Origins of Chemo- and Regioselectivities of Ru(II)-Catalyzed
      Decarboxylative C-H Alkenylation of Aryl Carboxylic Acids with Alkynes: A
      Computational Study.
AB  - The mechanisms and chemo- and regioselectivities of Ru(II)-catalyzed
      decarboxylative C-H alkenylation of aryl carboxylic acids with alkynes were
      investigated with density functional theory (DFT) calculations. The catalytic
      cycle involves sequential carboxylate-directed C-H activation, alkyne insertion,
      decarboxylation and protonation. The facile tether-assisted decarboxylation step
      directs the intermediate toward the desired decarboxylative alkenylation, instead
      of typical annulation and double alkenylation pathways. The decarboxylation
      barrier is very sensitive to the tether length, and only the seven-membered ring
      intermediate can selectively undergo the designed decarboxylation, suggesting a
      tether-dependent chemoselectivity. This tether-dependent chemoselectivity also
      applies to the alkyl tethers. In addition, the polarity of solvent is found to
      control the chemoselectivity between the decarboxylative alkenylation and [4 + 2]
      annulation. Solvent with low polarity (toluene) favors the decarboxylation
      pathway, leading to the decarboxylative alkenylation. Solvent with high polarity
      (methanol) favors the ionic stepwise C-O reductive elimination pathway, leading
      to the [4 + 2] annulation. To understand the origins of regioselectivity with
      asymmetric alkynes, the distortion/interaction analysis was applied to the alkyne
      insertion transition states, and led to a predictive frontier molecular orbital
      model. The asymmetric alkynes selectively use the terminal with the larger HOMO
      orbital coefficient to form the C-C bond in the insertion step.

PMID- 28498680
TI  - Spontaneous Orbital-Selective Mott Transitions and the Jahn-Teller Metal of
      A_{3}C_{60}.
AB  - The alkali-doped fullerides A_{3}C_{60} are half-filled three-orbital Hubbard
      systems which exhibit an unconventional superconducting phase next to a Mott
      insulator. While the pairing is understood to arise from an effectively negative
      Hund coupling, the highly unusual Jahn-Teller metal near the Mott transition,
      featuring both localized and itinerant electrons, has not been understood. This
      property is consistently explained by a previously unrecognized phenomenon: the
      spontaneous transition of multiorbital systems with negative Hund coupling into
      an orbital-selective Mott state. This symmetry-broken state, which has no
      ordinary orbital moment, is characterized by an orbital-dependent two-body
      operator (the double occupancy) or an orbital-dependent kinetic energy and may be
      regarded as a diagonal-order version of odd-frequency superconductivity. We
      propose that the recently discovered Jahn-Teller metal phase of Rb_{x}Cs_{3
      x}C_{60} is an experimental realization of this novel state of matter.

PMID- 28498679
TI  - Observation of the Isovector Giant Monopole Resonance via the
      ^{28}Si(^{10}Be,^{10}B^{*}[1.74  MeV]) Reaction at 100  AMeV.
AB  - The (^{10}Be,^{10}B^{*}[1.74  MeV]) charge-exchange reaction at 100  AMeV is
      presented as a new probe for isolating the isovector (DeltaT=1) nonspin-transfer
      (DeltaS=0) response of nuclei, with ^{28}Si being the first nucleus studied. By
      using a secondary ^{10}Be beam produced by fast fragmentation of ^{18}O nuclei at
      the NSCL Coupled Cyclotron Facility, applying the dispersion-matching technique
      with the S800 magnetic spectrometer to determine the excitation energy in
      ^{28}Al, and performing high-resolution gamma-ray tracking with the Gamma-Ray
      Energy Tracking In-beam Nuclear Array (GRETINA) to identify the 1022-keV gamma
      ray associated with the decay from the 1.74-MeV T=1 isobaric analog state in
      ^{10}B, a DeltaS=0 excitation-energy spectrum in ^{28}Al was extracted. Monopole
      and dipole contributions were determined through a multipole-decomposition
      analysis, and the isovector giant dipole resonance and isovector giant monopole
      resonance (IVGMR) were identified. The results show that this probe is a powerful
      tool for studying the elusive IVGMR, which is of interest for performing
      stringent tests of modern density functional theories at high excitation energies
      and for constraining the bulk properties of nuclei and nuclear matter. The
      extracted distributions were compared with theoretical calculations based on the
      normal-modes formalism and the proton-neutron relativistic time-blocking
      approximation. Calculated cross sections based on these strengths underestimate
      the data by about a factor of 2, which likely indicates deficiencies in the
      reaction calculations based on the distorted wave Born approximation.

PMID- 28498681
TI  - Bound States and Field-Polarized Haldane Modes in a Quantum Spin Ladder.
AB  - The challenge of one-dimensional systems is to understand their physics beyond
      the level of known elementary excitations. By high-resolution neutron
      spectroscopy in a quantum spin-ladder material, we probe the leading
      multiparticle excitation by characterizing the two-magnon bound state at zero
      field. By applying high magnetic fields, we create and select the singlet
      (longitudinal) and triplet (transverse) excitations of the fully spin-polarized
      ladder, which have not been observed previously and are close analogs of the
      modes anticipated in a polarized Haldane chain. Theoretical modeling of the
      dynamical response demonstrates our complete quantitative understanding of these
      states.

PMID- 28498682
TI  - Searching for Axionlike Particles with Ultraperipheral Heavy-Ion Collisions.
AB  - We show that ultraperipheral heavy-ion collisions at the Large Hadron Collider
      (LHC) can be used to search for axionlike particles with mass below 100 GeV. The
      Z^{4} enhanced photon-photon luminosity from the ions provides a large exclusive
      production rate, with a signature of a resonant pair of back-to-back photons and
      no other activity in the detector. In addition, we present both new and updated
      limits from recasting multiphoton searches at LEP II and the LHC, which are more
      stringent than those currently in the literature for the mass range 100 MeV to
      100 GeV.

PMID- 28498683
TI  - Probing CP Violation in h->tau^{-}tau^{+} at the LHC.
AB  - We propose a novel method to reconstruct event by event the full kinematics of
      the cascade decay process, h->tau^{+}tau^{-}->(pi^{+}nu[over -])(pi^{-}nu), which
      allows us to measure the tau^{+}tau^{-} spin correlation, a measure of the CP
      property of the Higgs boson. By noting that the tau^{+/-} momenta lie on the
      plane spanned by the accurately measured impact parameter and momentum vectors of
      charged pions, we can obtain the most likely momenta of the two missing neutrinos
      by using the probability distribution functions of the p[over ->]_{T} vector and
      the location of the primary vertex. A simple detector level simulation shows an
      excellent agreement between the reconstructed and the true kinematics, both in
      the tau^{+}tau^{-} and the pi^{+}pi^{-} rest frames. The method can be tested in
      Z->tau^{+}tau^{-} events, which should exhibit no correlation.

PMID- 28498684
TI  - Giant Thermal Magnetoresistance in Plasmonic Structures.
AB  - A giant thermal magnetoresistance is predicted for the electromagnetic transport
      of heat in magneto-optical plasmonic structures. In chains of InSb-Ag
      nanoparticles at room temperature, we find that the resistance can be increased
      by almost a factor of 2 with magnetic fields of 2 T. We show that this important
      change results from the strong spectral dependence of localized surface waves on
      the magnitude of the magnetic field.

PMID- 28498685
TI  - PT-Symmetric Scattering in Flow Duct Acoustics.
AB  - We show theoretically and experimentally that the propagation of an acoustic wave
      in an airflow duct going through a pair of diaphragms, with equivalent amounts of
      mean-flow-induced effective gain and loss, displays all the features of a parity
      time (PT) symmetric system. Using a scattering matrix formalism, we observe,
      experimentally, the properties which reflect the PT symmetry of the scattering
      acoustical system: the existence of spontaneous symmetry breaking with symmetry
      broken pairs of scattering eigenstates showing amplification and reduction, and
      the existence of points with unidirectional invisibility.

PMID- 28498687
TI  - Effect of Compactified Dimensions and Background Magnetic Fields on the Phase
      Structure of SU(N) Gauge Theories.
AB  - We discuss the properties of non-Abelian gauge theories formulated on manifolds
      with compactified dimensions and in the presence of fermionic fields coupled to
      magnetic backgrounds. We show that different phases may emerge, corresponding to
      different realizations of center symmetry and translational invariance, depending
      on the compactification radius and on the magnitude of the magnetic field. Our
      discussion then focuses on the case of an SU(3) gauge theory in four dimensions
      with fermions fields in the fundamental representation, for which we provide some
      exploratory numerical lattice results.

PMID- 28498686
TI  - Intense-Laser Solid State Physics: Unraveling the Difference between
      Semiconductors and Dielectrics.
AB  - Experiments on intense laser driven dielectrics have revealed population transfer
      to the conduction band to be oscillatory in time. This is in stark contrast to
      ionization in semiconductors and is currently unexplained. Current ionization
      theories neglect coupling between the valence and conduction band and therewith,
      the dynamic Stark shift. Our single-particle analysis identifies this as a
      potential reason for the different ionization behavior. The dynamic Stark shift
      increases the band gap with increasing laser intensities, thus suppressing
      ionization to an extent where virtual population oscillations become dominant.
      The dynamic Stark shift plays a role dominantly in dielectrics which, due to the
      larger band gap, can be exposed to significantly higher laser intensities.

PMID- 28498688
TI  - Antiferromagnetic Correlations in Two-Dimensional Fermionic Mott-Insulating and
      Metallic Phases.
AB  - We experimentally study the emergence of antiferromagnetic correlations between
      ultracold fermionic atoms in a two-dimensional optical lattice with decreasing
      temperature. We determine the uniform magnetic susceptibility of the two
      dimensional Hubbard model from simultaneous measurements of the in situ density
      distribution of both spin components. At half filling and strong interactions our
      data approach the Heisenberg model of localized spins with antiferromagnetic
      correlations. Moreover, we observe a fast decay of magnetic correlations when
      doping the system away from half filling.

PMID- 28498689
TI  - Evidence for a Nematic Phase in La_{1.75}Sr_{0.25}NiO_{4}.
AB  - Determining the nature of electronic states in doped Mott insulators remains a
      challenging task. In the case of tetragonal La_{2-x}Sr_{x}NiO_{4}, the occurrence
      of diagonal charge and spin stripe order in the ground state is now well
      established. In contrast, the nature of the high-temperature "disordered" state
      from which the stripe order develops has long been a subject of controversy, with
      considerable speculation regarding a polaronic liquid. Following the recent
      detection of dynamic charge stripes, we use neutron scattering measurements on an
      x=0.25 crystal to demonstrate that the dispersion of the charge-stripe
      excitations is anisotropic. This observation provides compelling evidence for the
      presence of electronic nematic order.

PMID- 28498690
TI  - Nonexponential Decoherence and Subdiffusion in Atom-Optics Kicked Rotor.
AB  - Quantum systems lose coherence upon interaction with the environment and tend
      towards classical states. Quantum coherence is known to exponentially decay in
      time so that macroscopic quantum superpositions are generally unsustainable. In
      this work, slower than exponential decay of coherences is experimentally realized
      in an atom-optics kicked rotor system subjected to nonstationary Levy noise in
      the applied kick sequence. The slower coherence decay manifests in the form of
      quantum subdiffusion that can be controlled through the Levy exponent. The
      experimental results are in good agreement with the analytical estimates and
      numerical simulations for the mean energy growth and momentum profiles of an atom
      optics kicked rotor.

PMID- 28498691
TI  - Electron-Scale Quadrants of the Hall Magnetic Field Observed by the
      Magnetospheric Multiscale spacecraft during Asymmetric Reconnection.
AB  - An in situ measurement at the magnetopause shows that the quadrupole pattern of
      the Hall magnetic field, which is commonly observed in a symmetric reconnection,
      is still evident in an asymmetric component reconnection, but the two quadrants
      adjacent to the magnetosphere are strongly compressed into the electron scale and
      the widths of the remaining two quadrants are still ion scale. The bipolar Hall
      electric field pattern generally created in a symmetric reconnection is replaced
      by a unipolar electric field within the electron-scale quadrants. Furthermore, it
      is concluded that the spacecraft directly passed through the inner electron
      diffusion region based on the violation of the electron frozen-in condition, the
      energy dissipation, and the slippage between the electron flow and the magnetic
      field. Within the inner electron diffusion region, magnetic energy was released
      and accumulated simultaneously, and it was accumulated in the perpendicular
      directions while dissipated in the parallel direction. The localized thinning of
      the current sheet accounts for the energy accumulation in a reconnection.

PMID- 28498692
TI  - Ideal Magnetic Dipole Scattering.
AB  - We introduce the concept of tunable ideal magnetic dipole scattering, where a
      nonmagnetic nanoparticle scatters light as a pure magnetic dipole. High
      refractive index subwavelength nanoparticles usually support both electric and
      magnetic dipole responses. Thus, to achieve ideal magnetic dipole scattering one
      has to suppress the electric dipole response. Such a possibility was recently
      demonstrated for the so-called anapole mode, which is associated with zero
      electric dipole scattering. By spectrally overlapping the magnetic dipole
      resonance with the anapole mode, we achieve ideal magnetic dipole scattering in
      the far field with tunable strong scattering resonances in the near infrared
      spectrum. We demonstrate that such a condition can be realized at least for two
      subwavelength geometries. One of them is a core-shell nanosphere consisting of a
      Au core and silicon shell. It can be also achieved in other geometries, including
      nanodisks, which are compatible with current nanofabrication technology.

PMID- 28498693
TI  - Publisher's Note: Probing the Scale Invariance of the Inflationary Power Spectrum
      in Expanding Quasi-Two-Dimensional Dipolar Condensates [Phys. Rev. Lett. 118,
      130404 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.130404.

PMID- 28498694
TI  - Spectrum of the Nuclear Environment for GaAs Spin Qubits.
AB  - Using a singlet-triplet spin qubit as a sensitive spectrometer of the GaAs
      nuclear spin bath, we demonstrate that the spectrum of Overhauser noise agrees
      with a classical spin diffusion model over 6 orders of magnitude in frequency,
      from 1 mHz to 1 kHz, is flat below 10 mHz, and falls as 1/f^{2} for frequency f?1
      Hz. Increasing the applied magnetic field from 0.1 to 0.75 T suppresses electron
      mediated spin diffusion, which decreases the spectral content in the 1/f^{2}
      region and lowers the saturation frequency, each by an order of magnitude,
      consistent with a numerical model. Spectral content at megahertz frequencies is
      accessed using dynamical decoupling, which shows a crossover from the few-pulse
      regime (?16pi pulses), where transverse Overhauser fluctuations dominate
      dephasing, to the many-pulse regime (?32 pi pulses), where longitudinal
      Overhauser fluctuations with a 1/f spectrum dominate.

PMID- 28498695
TI  - Ab Initio Green-Kubo Approach for the Thermal Conductivity of Solids.
AB  - We herein present a first-principles formulation of the Green-Kubo method that
      allows the accurate assessment of the phonon thermal conductivity of solid
      semiconductors and insulators in equilibrium ab initio molecular dynamics
      calculations. Using the virial for the nuclei, we propose a unique ab initio
      definition of the heat flux. Accurate size and time convergence are achieved
      within moderate computational effort by a robust, asymptotically exact
      extrapolation scheme. We demonstrate the capabilities of the technique by
      investigating the thermal conductivity of extreme high and low heat conducting
      materials, namely, Si (diamond structure) and tetragonal ZrO_{2}.

PMID- 28498696
TI  - Hyperfine and Spin-Orbit Coupling Effects on Decay of Spin-Valley States in a
      Carbon Nanotube.
AB  - The decay of spin-valley states is studied in a suspended carbon nanotube double
      quantum dot via the leakage current in Pauli blockade and via dephasing and
      decoherence of a qubit. From the magnetic field dependence of the leakage
      current, hyperfine and spin-orbit contributions to relaxation from blocked to
      unblocked states are identified and explained quantitatively by means of a simple
      model. The observed qubit dephasing rate is consistent with the hyperfine
      coupling strength extracted from this model and inconsistent with dephasing from
      charge noise. However, the qubit coherence time, although longer than previously
      achieved, is probably still limited by charge noise in the device.

PMID- 28498697
TI  - Single Nodal Loop of Accidental Degeneracies in Minimal Symmetry: Triclinic
      CaAs_{3}.
AB  - The existence of closed loops of degeneracies in crystals has been intimately
      connected with associated crystal symmetries, raising the following question:
      What is the minimum symmetry required for topological character, and can one find
      an example? Triclinic CaAs_{3}, in the space group P1[over -] with only a center
      of inversion, has been found to display, without need for tuning, a nodal loop of
      accidental degeneracies with topological character, centered on one face of the
      Brillouin zone that is otherwise fully gapped. The small loop is very flat in
      energy, yet is cut four times by the Fermi energy, a condition that results in an
      intricate repeated touching of inversion related pairs of Fermi surfaces at Weyl
      points. Spin-orbit coupling lifts the fourfold degeneracy along the loop, leaving
      trivial Kramers pairs. With its single nodal loop that emerges without protection
      from any point group symmetry, CaAs_{3} represents the primal "hydrogen atom" of
      nodal loop systems.

PMID- 28498698
TI  - Topological Phases of Parafermions: A Model with Exactly Solvable Ground States.
AB  - Parafermions are emergent excitations that generalize Majorana fermions and can
      also realize topological order. In this Letter, we present a nontrivial and quasi
      exactly-solvable model for a chain of parafermions in a topological phase. We
      compute and characterize the ground-state wave functions, which are matrix
      product states and have a particularly elegant interpretation in terms of Fock
      parafermions, reflecting the factorized nature of the ground states. Using these
      wave functions, we demonstrate analytically several signatures of topological
      order. Our study provides a starting point for the nonapproximate study of
      topological one-dimensional parafermionic chains with spatial inversion and time
      reversal symmetry in the absence of strong edge modes.

PMID- 28498699
TI  - Interaction-Driven Shift and Distortion of a Flat Band in an Optical Lieb
      Lattice.
AB  - We report the momentum-resolved measurement of Bloch bands in an optical Lieb
      lattice for a Bose-Einstein condensate (BEC). A BEC in the lattice is transported
      to a desired quasimomentum by applying a constant force. The energy dispersion of
      the lowest band is obtained by integrating measured group velocities. We also
      measure the gap from the lowest band to the higher bands with the same
      quasimomentum, which can be extracted from the oscillation of the sublattice
      populations after preparing a superposition of the band eigenstates. We show that
      the experimental results agree with a band calculation based on the Bogoliubov
      approximation. It is revealed that the second band, which should be flat in a
      single-particle description, is shifted and, in particular, distorted around the
      Brillouin zone edge as the interaction strength increases.

PMID- 28498700
TI  - Antiferroquadrupolar Order and Rotational Symmetry Breaking in a Generalized
      Bilinear-Biquadratic Model on a Square Lattice.
AB  - The magnetic and nematic properties of the iron chalcogenides have recently been
      the subject of intense interest. Motivated by the proposed antiferroquadrupolar
      and Ising-nematic orders for the bulk FeSe, we study the phase diagram of an S=1
      generalized bilinear-biquadratic model with multineighbor interactions. We find a
      large parameter regime for a (pi, 0) antiferroquadrupolar phase, showing how
      quantum fluctuations stabilize it by lifting an infinite degeneracy of certain
      semiclassical states. Evidence for this C_{4}-symmetry-breaking quadrupolar phase
      is also provided by an unbiased density matrix renormalization group analysis. We
      discuss the implications of our results for FeSe and related iron-based
      superconductors.

PMID- 28498701
TI  - Fast Low-to-High Confinement Mode Bifurcation Dynamics in a Tokamak Edge Plasma
      Gyrokinetic Simulation.
AB  - Transport barrier formation and its relation to sheared flows in fluids and
      plasmas are of fundamental interest in various natural and laboratory
      observations and of critical importance in achieving an economical energy
      production in a magnetic fusion device. Here we report the first observation of
      an edge transport barrier formation event in an electrostatic gyrokinetic
      simulation carried out in a realistic diverted tokamak edge geometry under strong
      forcing by a high rate of heat deposition. The results show that turbulent
      Reynolds-stress-driven sheared E*B flows act in concert with neoclassical orbit
      loss to quench turbulent transport and form a transport barrier just inside the
      last closed magnetic flux surface.

PMID- 28498702
TI  - Anomalous de Haas-van Alphen Effect in InAs/GaSb Quantum Wells.
AB  - The de Haas-van Alphen effect describes the periodic oscillation of the
      magnetization in a material as a function of an inverse applied magnetic field.
      It forms the basis of a well established procedure for measuring Fermi surface
      properties, and its observation is typically taken as a direct signature of a
      system being metallic. However, certain insulators can show similar oscillations
      of the magnetization from quantization of the energies of electron states in
      filled bands. Recently, the theory of such an anomalous dHvAE (AdHvAE) was worked
      out, but there has not yet been a clear experimental observation. Here, we show
      that the inverted narrow gap regime of InAs/GaSb quantum wells is an ideal
      platform for the observation of the AdHvAE. From our microscopic calculations, we
      make quantitative predictions for the relevant magnetic field and temperature
      regimes, and we describe unambiguous experimental signatures.

PMID- 28498703
TI  - Realization of a Cascaded Quantum System: Heralded Absorption of a Single Photon
      Qubit by a Single-Electron Charged Quantum Dot.
AB  - Photonic losses pose a major limitation for the implementation of a quantum state
      transfer between nodes of a quantum network. A measurement that heralds a
      successful transfer without revealing any information about the qubit may
      alleviate this limitation. Here, we demonstrate the heralded absorption of a
      single photonic qubit, generated by a single neutral quantum dot, by a single
      electron charged quantum dot that is located 5 m away. The transfer of quantum
      information to the spin degree of freedom takes place upon the emission of a
      photon; for a properly chosen or prepared quantum dot, the detection of this
      photon yields no information about the qubit. We show that this process can be
      combined with local operations optically performed on the destination node by
      measuring classical correlations between the absorbed photon color and the final
      state of the electron spin. Our work suggests alternative avenues for the
      realization of quantum information protocols based on cascaded quantum systems.

PMID- 28498704
TI  - Slip Morphology of Elastic Strips on Frictional Rigid Substrates.
AB  - The morphology of an elastic strip subject to vertical compressive stress on a
      frictional rigid substrate is investigated by a combination of theory and
      experiment. We find a rich variety of morphologies, which-when the bending
      elasticity dominates over the effect of gravity-are classified into three
      distinct types of states: pinned, partially slipped, and completely slipped,
      depending on the magnitude of the vertical strain and the coefficient of static
      friction. We develop a theory of elastica under mixed clamped-hinged boundary
      conditions combined with the Coulomb-Amontons friction law and find excellent
      quantitative agreement with simulations and controlled physical experiments. We
      also discuss the effect of gravity in order to bridge the difference in the
      qualitative behaviors of stiff strips and flexible strings or ropes. Our study
      thus complements recent work on elastic rope coiling and takes a significant step
      towards establishing a unified understanding of how a thin elastic object
      interacts vertically with a solid surface.

PMID- 28498705
TI  - Incoherence-Mediated Remote Synchronization.
AB  - In previously identified forms of remote synchronization between two nodes, the
      intermediate portion of the network connecting the two nodes is not synchronized
      with them but generally exhibits some coherent dynamics. Here we report on a
      network phenomenon we call incoherence-mediated remote synchronization (IMRS), in
      which two noncontiguous parts of the network are identically synchronized while
      the dynamics of the intermediate part is statistically and information
      theoretically incoherent. We identify mirror symmetry in the network structure as
      a mechanism allowing for such behavior, and show that IMRS is robust against
      dynamical noise as well as against parameter changes. IMRS may underlie neuronal
      information processing and potentially lead to network solutions for encryption
      key distribution and secure communication.

PMID- 28498706
TI  - Sisyphus Laser Cooling of a Polyatomic Molecule.
AB  - We perform magnetically assisted Sisyphus laser cooling of the triatomic free
      radical strontium monohydroxide (SrOH). This is achieved with principal optical
      cycling in the rotationally closed P(N^{''}=1) branch of either the X[over
      ~]^{2}Sigma^{+}(000)<->A[over ~]^{2}Pi_{1/2}(000) or the X[over
      ~]^{2}Sigma^{+}(000)<->B[over ~]^{2}Sigma^{+}(000) vibronic transitions.
      Molecules lost into the excited vibrational states during the cooling process are
      repumped back through the B[over ~](000) state for both the (100) level of the Sr
      O stretching mode and the (02^{0}0) level of the bending mode. The transverse
      temperature of a SrOH molecular beam is reduced in one dimension by 2 orders of
      magnitude to ~750  MUK. This approach opens a path towards creating a variety of
      ultracold polyatomic molecules by means of direct laser cooling.

PMID- 28498707
TI  - Electronic Phase Separation and Dramatic Inverse Band Renormalization in the
      Mixed-Valence Cuprate LiCu_{2}O_{2}.
AB  - We measured, by angle-resolved photoemission spectroscopy, the electronic
      structure of LiCu_{2}O_{2}, a mixed-valence cuprate where planes of Cu(I)
      (3d^{10}) ions are sandwiched between layers containing one-dimensional edge
      sharing Cu(II) (3d^{9}) chains. We find that the Cu(I)- and Cu(II)-derived
      electronic states form separate electronic subsystems, in spite of being coupled
      by bridging O ions. The valence band, of the Cu(I) character, disperses within
      the charge-transfer gap of the strongly correlated Cu(II) states, displaying an
      unprecedented 250% broadening of the bandwidth with respect to the predictions of
      density functional theory. Our observation is at odds with the widely accepted
      tenet of many-body theory that correlation effects generally yield narrower bands
      and larger electron masses and suggests that present-day electronic structure
      techniques provide an intrinsically inappropriate description of ligand-to-d
      hybridizations in late transition metal oxides.

PMID- 28498708
TI  - Supercurrents in Unidirectional Channels Originate from Information Transfer in
      the Opposite Direction: A Theoretical Prediction.
AB  - It has been thought that the long chiral edge channels cannot support any
      supercurrent between the superconducting electrodes. We show theoretically that
      the supercurrent can be mediated by a nonlocal interaction that facilitates a
      long-distance information transfer in the direction opposite of electron flow. We
      compute the supercurrent for several interaction models, including that of an
      external circuit.

PMID- 28498709
TI  - Topological Magnon Bands and Unconventional Superconductivity in Pyrochlore
      Iridate Thin Films.
AB  - We theoretically study the magnetic properties of pyrochlore iridate bilayer and
      trilayer thin films grown along the [111] direction using a strong coupling
      approach. We find the ground state magnetic configurations on a mean field level
      and carry out a spin-wave analysis about them. In the trilayer case the ground
      state is found to be the all-in-all-out (AIAO) state, whereas the bilayer has a
      deformed AIAO state. For all parameters of the spin-orbit coupled Hamiltonian we
      study, the lowest magnon band in the trilayer case has a nonzero Chern number. In
      the bilayer case we also find a parameter range with nonzero Chern numbers. We
      calculate the magnon Hall response for both geometries, finding a striking sign
      change as a function of temperature. Using a slave-boson mean-field theory we
      study the doping of the trilayer system and discover an unconventional time
      reversal symmetry broken d+id superconducting state. Our study complements prior
      work in the weak coupling limit and suggests that the [111] grown thin film
      pyrochlore iridates are a promising candidate for topological properties and
      unconventional orders.

PMID- 28498711
TI  - Projector Quantum Monte Carlo Method for Nonlinear Wave Functions.
AB  - We reformulate the projected imaginary-time evolution of the full configuration
      interaction quantum Monte Carlo method in terms of a Lagrangian minimization.
      This naturally leads to the admission of polynomial complex wave function
      parametrizations, circumventing the exponential scaling of the approach. While
      previously these functions have traditionally inhabited the domain of variational
      Monte Carlo approaches, we consider recent developments for the identification of
      deep-learning neural networks to optimize this Lagrangian, which can be written
      as a modification of the propagator for the wave function dynamics. We
      demonstrate this approach with a form of tensor network state, and use it to find
      solutions to the strongly correlated Hubbard model, as well as its application to
      a fully periodic ab initio graphene sheet. The number of variables which can be
      simultaneously optimized greatly exceeds alternative formulations of variational
      Monte Carlo methods, allowing for systematic improvability of the wave function
      flexibility towards exactness for a number of different forms, while blurring the
      line between traditional variational and projector quantum Monte Carlo
      approaches.

PMID- 28498712
TI  - Fast Diffusion of Long Guest Rods in a Lamellar Phase of Short Host Particles.
AB  - We investigate the dynamic behavior of long guest rodlike particles immersed in
      liquid crystalline phases formed by shorter host rods, tracking both guest and
      host particles by fluorescence microscopy. Counterintuitively, we evidence that
      long rods diffuse faster than short rods forming the one-dimensional ordered
      smectic-A phase. This results from the larger and noncommensurate size of the
      guest particles as compared to the wavelength of the energy landscape set by the
      lamellar stack of liquid slabs. The long guest particles are also shown to be
      still mobile in the crystalline smectic-B phase, as they generate their own voids
      in the adjacent layers.

PMID- 28498713
TI  - Improved Sensing with a Single Qubit.
AB  - We consider quantum metrology with arbitrary prior knowledge of the parameter. We
      demonstrate that a single sensing two-level system can act as a virtual
      multilevel system that offers increased sensitivity in a Bayesian single-shot
      metrology scenario, and that allows one to estimate (arbitrary) large parameter
      values by avoiding phase wraps. This is achieved by making use of additional
      degrees of freedom or auxiliary systems not participating in the sensing process.
      The joint system is manipulated by intermediate control operations in such a way
      that an effective Hamiltonian, with an arbitrary spectrum, is generated that
      mimics the spectrum of a multisystem interacting with the field. We show how to
      use additional internal degrees of freedom of a single trapped ion to achieve a
      high-sensitivity magnetic field sensor for fields with arbitrary prior knowledge.

PMID- 28498710
TI  - Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA
      Pathfinder.
AB  - We report on electrostatic measurements made on board the European Space Agency
      mission LISA Pathfinder. Detailed measurements of the charge-induced
      electrostatic forces exerted on free-falling test masses (TMs) inside the
      capacitive gravitational reference sensor are the first made in a relevant
      environment for a space-based gravitational wave detector. Employing a
      combination of charge control and electric-field compensation, we show that the
      level of charge-induced acceleration noise on a single TM can be maintained at a
      level close to 1.0  fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band
      that is crucial to an observatory such as the Laser Interferometer Space Antenna
      (LISA). Using dedicated measurements that detect these effects in the
      differential acceleration between the two test masses, we resolve the stochastic
      nature of the TM charge buildup due to interplanetary cosmic rays and the TM
      charge-to-force coupling through stray electric fields in the sensor. All our
      measurements are in good agreement with predictions based on a relatively simple
      electrostatic model of the LISA Pathfinder instrument.

PMID- 28498714
TI  - Mitigation of the Hose Instability in Plasma-Wakefield Accelerators.
AB  - Current models predict the hose instability to crucially limit the applicability
      of plasma-wakefield accelerators. By developing an analytical model which
      incorporates the evolution of the hose instability over long propagation
      distances, this work demonstrates that the inherent drive-beam energy loss, along
      with an initial beam-energy spread, detunes the betatron oscillations of beam
      electrons and thereby mitigates the instability. It is also shown that tapered
      plasma profiles can strongly reduce initial hosing seeds. Hence, we demonstrate
      that the propagation of a drive beam can be stabilized over long propagation
      distances, paving the way for the acceleration of high-quality electron beams in
      plasma-wakefield accelerators. We find excellent agreement between our models and
      particle-in-cell simulations.

PMID- 28498715
TI  - Anderson Localization of Ultracold Atoms: Where is the Mobility Edge?
AB  - Recent experiments in noninteracting ultracold atoms in three-dimensional speckle
      potentials have yielded conflicting results regarding the so-called mobility
      edge, i.e., the energy threshold separating Anderson localized from diffusive
      states. At the same time, there are theoretical indications that most
      experimental data overestimate this critical energy, sometimes by a large amount.
      Using extensive numerical simulations, we show that the effect of anisotropy in
      the spatial correlations of realistic disorder configurations alone is not
      sufficient to explain the experimental data. In particular, we find that the
      mobility edge obeys a universal scaling behavior, independently of the speckle
      geometry.

PMID- 28498717
TI  - Melatonin as a versatile molecule to design novel multitarget hybrids against
      neurodegeneration.
AB  - Melatonin is an indoleamine produced mainly in the pineal gland. The natural
      decline of melatonin levels with aging strongly contributes to the development of
      neurodegenerative disorders. Pleiotropic actions displayed by melatonin prevent
      several processes involved in neurodegeneration such as neuroinflammation,
      oxidative stress, excitotoxicity and/or apoptosis. This review focuses on a
      number of melatonin hybrids resulting from the juxtaposition of tacrine,
      berberine, tamoxifen, curcumin, N,N-dibenzyl(N-methyl)amine, among others, with
      potential therapeutic effects for the treatment of neurodegenerative diseases.

PMID- 28498716
TI  - Chronotype distribution in professional rugby players: Evidence for the
      environment hypothesis?
AB  - Individual sport athletes have been shown to comprise unusually high proportions
      of morning-types (MTs) coupled with a higher prevalence of the morningness
      associated PERIOD3 variable number tandem repeat (VNTR) allele, PER35. The degree
      to which type of sport selected is influenced by either chronotype or genotype,
      or the extent to which sporting environment contributes to chronotype is unclear.
      The aim of this study was to assess chronotype and PER3 VNTR polymorphism
      frequencies in team sport players and non-athletic controls. South African male
      Super Rugby players (RUG, n = 120) and a control population of males with
      habitually low levels of physical activity (defined as exercise no more than
      twice a week; CON, n = 117) took part in this study. Participants completed the
      Horne-Ostberg morningness-eveningness questionnaire to determine chronotype and
      donated buccal cell or blood samples from which PER3 VNTR genotype was
      established. There were more MTs in the RUG (47%) than CON group (23%, p <
      0.001), more evening-types in the CON group (18%) compared to the RUG group (3%,
      p < 0.001), but no differences in PER3 VNTR genotype (p = 0.619) or allele (p =
      0.758) frequencies. In both groups, more people carried the PER34 allele (RUG:
      63%, CON: 62%). Chronotype was associated with genotype in the CON (p = 0.004)
      but not the RUG group (p = 0.895). Unlike the individual sport endurance athletes
      previously studied in whom the PER35 allele predominated, the PER3 VNTR genotype
      distribution in these team sport players was similar to that of the general
      population. We hypothesise that the absence of any chronotype-genotype
      relationship in these rugby players is because their diurnal preference is
      shifted towards morningness through habitual athletic behaviour.

PMID- 28498718
TI  - Effects of regular cannabis use on neurocognition, brain structure, and function:
      a systematic review of findings in adults.
AB  - BACKGROUND: Cannabis is the most used illicit drug worldwide. The long-standing
      consequences for the central nervous system associated with frequent cannabis use
      have not been well delineated and should be determined. OBJECTIVE: To review
      recent studies on the effects of regular cannabis use regarding its effects on
      cognition, brain structure, and function in adults. METHODS: A systematic
      literature review was conducted by performing electronic searches in the PubMed,
      LILACS, and SciELO databases (2010-2016). The initial search identified 898
      records. They were evaluated for relevance according to the inclusion and
      exclusion criteria and 56 studies were included. RESULTS: The neuropsychological
      studies provide evidence for subtle cognitive deficits at least 7 days after
      heavy cannabis use. The structural neuroimaging studies show growing evidence of
      abnormalities in hippocampus volume and gray matter density of cannabis users
      relative to controls; however, morphological changes in other brain regions are
      more controversial. The functional neuroimaging studies suggest an altered
      pattern of brain activity associated with cannabis use. CONCLUSION: Although
      there are several limitations for study comparison and substantial heterogeneity
      in the findings, the present review suggests that regular cannabis use is
      associated with mild cognitive changes in addition to structural and functional
      alterations in the brain in adults. The morphological alterations could
      ultimately affect brain organization and function, but the associated time course
      for neuronal recovery as well as the real impact on cognitive functioning remain
      unknown. Also, it is still unclear whether the identified alterations are as a
      consequence of or precede cannabis use.

PMID- 28498719
TI  - Surgical anatomy of the pelvic vasculature, with particular reference to
      acetabular screw fixation in cementless total hip arthroplasty in Asian
      population.
AB  - PURPOSE: Pelvic vascular injury is a serious complication associated with
      acetabular component setting with screw fixation in cementless total hip
      arthroplasty (THA). In this study, we investigated the safety zone for acetabular
      component setting with screw fixation in cementless THA as a means to prevent
      pelvic vascular injury. METHODS: Thirty left hip joints of Japanese cadavers (11
      males and 19 females) were analyzed. We used a hemispherical measuring cup with
      52 guide holes designed to allow vertical insertion of a Kirschner wire. After
      the measuring cup was placed on the acetabulum, the Kirschner wire was inserted
      from each guide hole to examine the anatomical relationship between the
      acetabulum and the pelvic vessels. We calculated the frequency of pelvic vessel
      punctures and measured the distance from the acetabular surface to the pelvic
      vessels at each guide hole. RESULTS: Our findings revealed that pelvic vessels do
      not exist in certain parts of the posterior area of the acetabulum. Furthermore,
      in this area, intrapelvic vessels are either lacking or located at a distance
      >=31 mm from the surface of the acetabulum. CONCLUSION: The posterior area of the
      acetabulum, excluding its central portion, appeared to be the safety zone for
      acetabular screw fixation in Japanese cadavers.

PMID- 28498720
TI  - Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress
      Over the Last Decade.
AB  - Peptides and proteins have been found to possess an inherent tendency to convert
      from their native functional states into intractable amyloid aggregates. This
      phenomenon is associated with a range of increasingly common human disorders,
      including Alzheimer and Parkinson diseases, type II diabetes, and a number of
      systemic amyloidoses. In this review, we describe this field of science with
      particular reference to the advances that have been made over the last decade in
      our understanding of its fundamental nature and consequences. We list the
      proteins that are known to be deposited as amyloid or other types of aggregates
      in human tissues and the disorders with which they are associated, as well as the
      proteins that exploit the amyloid motif to play specific functional roles in
      humans. In addition, we summarize the genetic factors that have provided insight
      into the mechanisms of disease onset. We describe recent advances in our
      knowledge of the structures of amyloid fibrils and their oligomeric precursors
      and of the mechanisms by which they are formed and proliferate to generate
      cellular dysfunction. We show evidence that a complex proteostasis network
      actively combats protein aggregation and that such an efficient system can fail
      in some circumstances and give rise to disease. Finally, we anticipate the
      development of novel therapeutic strategies with which to prevent or treat these
      highly debilitating and currently incurable conditions.

PMID- 28498721
TI  - Mechanisms of Deubiquitinase Specificity and Regulation.
AB  - Protein ubiquitination is one of the most powerful posttranslational
      modifications of proteins, as it regulates a plethora of cellular processes in
      distinct manners. Simple monoubiquitination events coexist with more complex
      forms of polyubiquitination, the latter featuring many different chain
      architectures. Ubiquitin can be subjected to further posttranslational
      modifications (e.g., phosphorylation and acetylation) and can also be part of
      mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitin
      related modifier) or NEDD8 (neural precursor cell expressed, developmentally
      downregulated 8). Together, cellular ubiquitination events form a sophisticated
      and versatile ubiquitin code. Deubiquitinases (DUBs) reverse ubiquitin signals
      with equally high sophistication. In this review, we conceptualize the many
      layers of specificity that DUBs encompass to control the ubiquitin code and
      discuss examples in which DUB specificity has been understood at the molecular
      level. We further discuss the many mechanisms of DUB regulation with a focus on
      those that modulate catalytic activity. Our review provides a framework to tackle
      lingering questions in DUB biology.

PMID- 28498722
TI  - Positive affective processes underlie positive health behaviour change.
AB  - Positive health behaviours such as physical activity can prevent or reverse many
      chronic conditions, yet a majority of people fall short of leading a healthy
      lifestyle. Recent discoveries in affective science point to promising approaches
      to circumvent barriers to lifestyle change. Here, we present a new theoretical
      framework that integrates scientific knowledge about positive affect with that on
      implicit processes. The upward spiral theory of lifestyle change explains how
      positive affect can facilitate long-term adherence to positive health behaviours.
      The inner loop of this spiral model identifies nonconscious motives as a central
      mechanism of behavioural maintenance. Positive affect experienced during health
      behaviours increases incentive salience for cues associated with those
      behaviours, which in turn, implicitly guides attention and the everyday decisions
      to repeat those behaviours. The outer loop represents the evidence-backed claim,
      based on Fredrickson's broaden-and-build theory, that positive affect builds a
      suite of endogenous resources, which may in turn amplify the positive affect
      experienced during positive health behaviours and strengthen the nonconscious
      motives. We offer published and preliminary evidence in favour of the theory,
      contrast it to other dominant theories of health behaviour change, and highlight
      attendant implications for interventions that merit testing.

PMID- 28498723
TI  - Advances in Preimplantation Genetic Testing for Monogenic Disease and Aneuploidy.
AB  - Genetic testing of preimplantation embryos promises to prevent monogenic disease
      in children born to at-risk couples, the transfer of unbalanced embryos to
      patients carrying a balanced translocation, and the use of aneuploid embryos
      created during in vitro fertilization. Technologies have evolved from
      fluorescence in situ hybridization to next-generation-sequencing-based aneuploidy
      screening and allow for simultaneous testing of multiple genetic abnormalities in
      a single biopsy. The field has also shifted away from polar body or blastomere
      biopsy and toward trophectoderm biopsy as the new standard. This review describes
      the multitude of available platforms and methodologies used in contemporary
      preimplantation genetic testing.

PMID- 28498724
TI  - Phonological patterns (templates) in 5p deletion syndrome.
AB  - Whole word phonological patterns (templates) in utterances produced by children
      with 5p deletion syndrome are analysed, addressing four questions: (1) Are
      children with 5p deletion syndrome able to generalise over words? (2) How does
      the template score of children with 5p deletion syndrome relate to those of
      typically developing children and of the target language? (3) How do the template
      scores relate to other phonological measures, PCC and consonant variegation? (4)
      What can the relationship between template scores and phonological measures tell
      us about templates? Children with 5p deletion syndrome are able to generalise
      over words, some to a target like extent, others generalise more than expected
      for their age. The template scores relate to other phonological measures, with
      two exceptions. The exceptions indicate that the template score of a child with
      articulatory difficulties may reflect more detailed representations of the words
      in memory than she is able to express.

PMID- 28498725
TI  - Evaluation of Abbott's BurstDR stimulation device for the treatment of chronic
      pain.
AB  - INTRODUCTION: Burst stimulation, as described by DeRidder, is a novel waveform
      made up of closely spaced, high-frequency electrical impulses delivered in
      packets, which are followed by a quiescent period or interburst interval.
      Electrically generated burst waveforms were initially designed to treat neural
      pathology in the auditory cortex and were later applied to the spinal cord
      through spinal cord stimulation (SCS) devices to treat chronic pain states. When
      Burst stimulation is applied to the spinal cord, the impulses travel to the
      thalamus and then diverge, targeting both the somatosensory cortex and the limbic
      system where they treat both the sensory, affective and attentional components of
      neuropathic pain. Areas covered: Literature examining clinical and basic research
      findings with the application of Burst stimulation to pathologically active
      central neural tissue was found using bibliographic databases including PubMed,
      Medline, Cochrane, Embase and Google Scholar. Expert commentary: Burst
      stimulation offers a salvage strategy for failed tonic spinal cord stimulation
      (tSCS), thus improving both quality of life and cost-effectiveness of SCS by
      reducing explant rates. The goal of this therapy is to use more than one waveform
      in the same device so that lost efficacy from tSCS can be salvaged.

PMID- 28498726
TI  - An Analysis of First-Grade Writing Profiles and Their Relationship to
      Compositional Quality.
AB  - To help all students meet the writing expectations of the Common Core State
      Standards, researchers need a deeper understanding of the characteristics of
      struggling writers. The purpose of this study was to explore the writing profiles
      of students including those who have or are at risk for writing disabilities.
      First-grade students ( N = 391) were assessed at the end of the school year using
      three writing assessments (spelling, sentence writing fluency, writing
      achievement). The researchers used latent profile analysis to identify students
      as fitting into one of five profiles (At Risk, Low Fluency, Low Writing, Average,
      and Above Average). Students also wrote narrative and descriptive texts that were
      scored multiple ways. The researchers used confirmatory factor analysis to
      identify four common factors: quality/length, spelling, mechanics, and syntax.
      Students in the At Risk profile wrote narratives and descriptions that scored
      lower on all aspects of writing when compared to students in the Average and
      Above Average profiles. These findings provide further evidence of the distinct
      difference among writers as early as first grade, and they offer insight into the
      characteristics of at-risk writers. The implications of these findings for
      instruction and assessment and directions for future research are described.

PMID- 28498727
TI  - Good Prognosis Went Badly: Fulminant Evolution of a 29-Year-Old Patient with
      Verrucous Carcinoma of the Cervix.
AB  - Verrucous carcinoma (VC) is a very rare variant of squamous cell carcinoma of the
      cervix, difficult to point out in histology because of its benign appearance. We
      present the case of a 29-year-old woman with a locally advanced cervical VC who
      underwent radiotherapy followed by radical hysterectomy. After local relapse and
      despite pelvic exenteration, her condition deteriorated. Treatment of choice in
      VC is surgery, because of the risk of anaplastic transformation under
      irradiation, raising the chances of distant spread and converting this rather
      benign-like type of cancer to an aggressive cancer.

PMID- 28498728
TI  - A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to
      control cell migration.
AB  - Cell migration is central to many developmental, physiologic and pathological
      processes, including cancer progression. The Ral GTPases (RalA and RalB) which
      act down-stream the Ras oncogenes, are key players in the coordination between
      membrane trafficking and actin polymerization. A major direct effector of Ral,
      the exocyst complex, works in polarized exocytosis and is at the center of
      multiple protein-protein interactions that support cell migration by promoting
      protrusion formation, front-rear polarization, and extra-cellular matrix
      degradation. In this review we describe the recent advancements in deciphering
      the molecular mechanisms underlying this role of Ral via exocyst on cell
      migration. Among others, we will discuss the recently identified cross-talk
      between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP
      SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the
      master regulator of protrusions. Next challenge will be to better characterize
      the dynamics in space and in time of these molecular interplays, to better
      understand the pleiotropic functions of Ral in both normal and cancer cells.

PMID- 28498729
TI  - The distinct function of Tep2 and Tep6 in the immune defense of Drosophila
      melanogaster against the pathogen Photorhabdus.
AB  - Previous and recent investigations on the innate immune response of Drosophila
      have identified certain mechanisms that promote pathogen elimination. However,
      the function of Thioester-containing proteins (TEPs) in the fly still remains
      elusive. Recently we have shown the contribution of TEP4 in the antibacterial
      immune defense of Drosophila against non-pathogenic E. coli, and the pathogens
      Photorhabdus luminescens and P. asymbiotica. Here we studied the function of Tep
      genes in both humoral and cellular immunity upon E. coli and Photorhabdus
      infection. We found that while Tep2 is induced after Photorhabdus and E. coli
      infection; Tep6 is induced by P. asymbiotica only. Moreover, functional ablation
      of hemocytes results in significantly low transcript levels of Tep2 and Tep6 in
      response to Photorhabdus. We show that Tep2 and Tep6 loss-of-function mutants
      have prolonged survival against P. asymbiotica, Tep6 mutants survive better the
      infection of P. luminescens, and both tep mutants are resistant to E. coli and
      Photorhabdus. We also find a distinct pattern of immune signaling pathway
      induction in E. coli or Photorhabdus infected Tep2 and Tep6 mutants. We further
      show that Tep2 and Tep6 participate in the activation of hemocytes in Drosophila
      responding to Photorhabdus. Finally, inactivation of Tep2 or Tep6 affects
      phagocytosis and melanization in flies infected with Photorhabdus. Our results
      indicate that distinct Tep genes might be involved in different yet crucial
      functions in the Drosophila antibacterial immune response.

PMID- 28498730
TI  - Exploring the Association of Maternal Adverse Childhood Experiences with Maternal
      Health and Child Behavior Following Intimate Partner Violence.
AB  - BACKGROUND: Adverse childhood experiences (ACEs) have been empirically linked to
      a host of negative health outcomes, both physical and psychosocial. Exposures to
      ACEs make individuals more susceptible to conditions such as cardiovascular
      disease, diabetes, cancers, and depression. Many of these conditions do not
      appear until sometime in adolescence or adulthood and have been linked to
      premature death. OBJECTIVE: This study explores the association between the
      number and type of exposure to ACEs in women (mothers) who experienced intimate
      partner violence and health outcomes. Specifically, it explores the association
      between maternal ACEs and maternal perceived health and maternal mental and
      behavioral health. This study also explores the association between ACEs and
      child behavior. METHODS: This analysis is part of a 7-year prospective study. A
      cohort of 300 mother-child pairs was assessed at baseline and every 4 months
      after reaching out for shelter or justice services for the very first time after
      being in an abusive intimate relationship. RESULTS: Data document individual
      mothers' ACE scores and show a trend at 12 months, 24 months, and is most
      significant at 36 months. Additionally, at 36 months, higher ACE scores were
      significantly associated with all child behavioral subscales (anxiety,
      depression, aggressive behavior, attention problems, internalizing,
      externalizing). CONCLUSION: The women in this study reported ACE scores
      consistently higher than national rates. Our data highlight the added benefit of
      using ACE criteria as a global prevention strategy to identify those most at risk
      for delayed mental and behavioral health issues and to intervene with supportive
      strategies and guided referrals as indicated.

PMID- 28498732
TI  - Early Writing Intervention: A Best Evidence Synthesis.
AB  - The purpose of this best evidence synthesis was to identify promising
      interventions that align with a theoretical model of early writing development,
      targeting three components of early writing: transcription, text generation, and
      self-regulation. We determined the extent to which these interventions are
      effective for children who struggle with early writing skills, by calculating
      effect sizes for group and single-subject designs, and we examined the overall
      quality of the research. Twenty-five studies met inclusion criteria. Among group
      design studies, mean effects (Hedge's g) ranged from 0.19 to 1.17 for measures of
      writing quantity and from 0.17 to 0.85 for measures of writing quality.
      Percentage of all nonoverlapping data for single-subject designs ranged from 83%
      to 100% for measures of writing quantity. Interventions with the strongest
      evidence of effects and highest methodological quality are described in detail.
      Recommendations for research and practice are provided.

PMID- 28498731
TI  - Tissue transglutaminase expression is necessary for adhesion, metastatic
      potential and cancer stemness of renal cell carcinoma.
AB  - Tissue transglutaminase (TG2) is the ubiquitously expressed member of
      transglutaminase family and shown to play a critical role in the development and
      progression of drug resistance malignancies. We have previously showed the
      association of TG2 upregulation with progression and metastasis of renal cell
      carcinoma (RCC) and low disease-free survival. In the present study we further
      investigate the role of TG2 in cell adhesion, migration and invasion of RCC by
      silencing TG2 expression in Caki-2 and A-498 primary site and Caki-1 and ACHN
      metastatic site RCC cell lines. Downregulation of TG2 expression led up to a 60%
      decrease in actin stress fiber formation and adhesion to beta 1 integrin (ITGB1)
      substrates fibronectin, collagen type I and laminin in both primary and
      metastatic site RCC cell lines. In addition, treatment with siRNAs against TG2
      impaired the migration capacity and cellular invasiveness of ITGB1 substrates in
      all 4 RCC cell lines. Lastly, the knockdown of TG2 in metastatic Caki-1 cells
      diminished the expression of CD44, CD73-and CD105 cancer stem cell-like markers.
      We conclude, for the first time, that TG2 expression is critical for cancer cell
      adhesion, migration, invasiveness and cancer cell-stemness during RCC progression
      and dissemination. Therefore, combined targeting of TG2 with drugs widely used in
      the treatment of RCC may be a promising therapeutic strategy for RCC.

PMID- 28498734
TI  - NeurHistAlert 23.

PMID- 28498733
TI  - Immunotherapy is different: Implications for vaccine clinical trial design.
AB  - Cancer Immunotherapetics differ fundamentally from most cancer therapies in that
      they involve manipulation of the immune system to induce an anti-tumor response.
      This fundamental difference results in differences in the pre-clinical and
      clinical development of immunotherapeutics. Even the regulatory culture of
      developing one drug at a time and demonstrating that it, when added to standard
      therapy, prolongs patient survival, is often not suitable for the development of
      effective immunotherapy regimens. In this commentary, we explore some of these
      differences and describe novel clinical trial designs which may be useful in
      immunotherapeutics regimen development.

PMID- 28498735
TI  - Critical Issues in the Understanding of Young Elementary School Students at Risk
      for Problems in Written Expression: Introduction to the Special Series.
AB  - In this introduction to the special series "Critical Issues in the Understanding
      of Young Elementary School Students at Risk for Problems in Written Expression,"
      we consider some of the contextual factors that have changed since a similar
      special issue was published in the Journal of Learning Disabilities in 2002. We
      also explore how the five articles included in this special series address the
      following important themes: early writing development, identification of students
      with writing difficulties, and effective interventions for struggling writers. In
      conclusion, we envision future directions to advance the field.

PMID- 28498736
TI  - ESVM Graz 2017 - Abstracts.

PMID- 28498737
TI  - Improved postpartum care after a participatory facilitation intervention in Dar
      es Salaam, Tanzania: a mixed method evaluation.
AB  - BACKGROUND: In order to improve the health and survival of mothers/newborns, the
      quality and attendance rates of postpartum care (PPC) must be increased,
      particularly in low-resource settings. OBJECTIVE: To describe outcomes of a
      collegial facilitation intervention to improve PPC in government-owned health
      institutions in a low-resource suburb in Dar es Salaam, Tanzania. METHODS: A
      before-and-after evaluation of an intervention and comparison group was conducted
      using mixed methods (focus group discussions, questionnaires, observations,
      interviews, and field-notes) at health institutions. Maternal and child health
      aiders, enrolled nurse midwives, registered nurse midwives, and medical and
      clinical officers participated. A collegial facilitation intervention was
      conducted and healthcare providers were organized in teams to improve PPC at
      their workplaces. Facilitators defined areas of improvement with colleagues and
      met regularly with a supervisor for support. RESULTS: The number of mothers
      visiting the institution for PPC increased in the intervention group. Some care
      actions were noted in more than 80% of the observations and mothers reported high
      satisfaction with care. In the comparison group, PPC continued to be next to non
      existent. The healthcare providers' knowledge increased in both groups but was
      higher in the intervention group. The t-test showed a significant difference in
      knowledge between the intervention and comparison groups and between before and
      after the intervention in both groups. The difference of differences for
      knowledge was 1.3. The providers perceived the intervention outcomes to include
      growing professional confidence/knowledge, improved PPC quality, and mothers'
      positive response. The quality grading was based on the national guidelines and
      involved nine experts and showed that none of the providers reached the level of
      good quality of care. CONCLUSIONS: The participatory facilitation intervention
      contributed to improved quality of PPC, healthcare providers' knowledge and
      professional confidence, awareness of PPC among mothers, and increased PPC
      attendance.

PMID- 28498738
TI  - Biogas production from anaerobic digestion of food waste and relevant air quality
      implications.
AB  - : Biopower can diversify energy supply and improve energy resiliency. Increases
      in biopower production from sustainable biomass can provide many economic and
      environmental benefits. For example, increasing biogas production through
      anaerobic digestion of food waste would increase the use of renewable fuels
      throughout California and add to its renewables portfolio. Although a biopower
      project will produce renewable energy, the process of producing bioenergy should
      harmonize with the goal of protecting public health. Meeting air emission
      requirements is paramount to the successful implementation of any biopower
      project. A case study was conducted by collecting field data from a wastewater
      treatment plant that employs anaerobic codigestion of fats, oils, and grease
      (FOG), food waste, and wastewater sludge, and also uses an internal combustion
      (IC) engine to generate biopower using the biogas. This research project
      generated scientific information on (a) quality and quantity of biogas from
      anaerobic codigestion of food waste and municipal wastewater sludge, (b) levels
      of contaminants in raw biogas that may affect beneficial uses of the biogas, (c)
      removal of the contaminants by the biogas conditioning systems, (d) emissions of
      NOx, SO2, CO, CO2, and methane, and (e) types and levels of air toxics present in
      the exhausts of the IC engine fueled by the biogas. The information is valuable
      to those who consider similar operations (i.e., co-digestion of food waste with
      municipal wastewater sludge and power generation using the produced biogas) and
      to support rulemaking decisions with regards to air quality issues for such
      applications. IMPLICATIONS: Full-scale operation of anaerobic codigestion of food
      waste with municipal sludge is viable, but it is still new. There is a lack of
      readily available scientific information on the quality of raw biogas, as well as
      on potential emissions from power generation using this biogas. This research
      developed scientific information with regard to quality and quantity of biogas
      from anaerobic co-digestion of food waste and municipal wastewater sludge, as
      well as impacts on air quality from biopower generation using this biogas. The
      need and performance of conditioning/pretreatment systems for biopower generation
      were also assessed.

PMID- 28498741
TI  - Growing Momentum for Sugar-Sweetened Beverage Campaigns and Policies: Costs and
      Considerations.

PMID- 28498739
TI  - Feasibility of a cardiovascular cohort in a Sub-Saharan Africa community:
      preliminary report of the pilot project TAHES (Tanve Health Study) in Benin.
AB  - BACKGROUND: Faced with the growing burden of cardiovascular disease (CVD)
      including atherosclerotic in Sub-Saharan Africa (SSA), the development of
      appropriate prediction tools, based on large cohorts, appears useful for
      prevention. OBJECTIVE: The objective of the pilot project TAHES (Tanve Health
      Study) was to explore the feasibility of a large cohort study focused on CVD and
      risk factors in Benin. METHODS: We implemented a prospective cohort over 2 years.
      The sample consisted of all people aged 25 years or older who had lived for at
      least the previous 6 months in the villages of Tanve or Dekanme. At baseline in
      February 2015, behaviours and medical histories were recorded using a
      standardized questionnaire adapted from the WHO Steps instrument; screening
      questionnaires for angina, claudication, congestive heart failure, and stroke
      were applied; anthropometric measures and fasting capillary blood glucose were
      taken. All participants were included in the follow-up phase. Surveillance of
      target CVD and deaths was implemented through a medical and a community network.
      RESULTS: A total of 1,195 participants were enrolled at baseline; women
      represented 65.5% and the median age was 39 years. The high participation rate
      (91.4%), the quality of baseline data, and the functionality of the events
      surveillance network over 8 months indicated good perspective for the feasibility
      of a large cohort. We recorded a 3.8% prevalence of daily smoking, 3.6% of
      harmful use of alcohol, 10.7% of obesity, 25.5% of high blood pressure, and 3.5%
      of diabetes. Prevalence of angina pectoris (2.7%), intermittent claudication
      (2.0%), congestive heart failure (0.9%), and stroke survival with motor
      impairment (30/00) were also recorded. Ten deaths occurred during the first 8
      months, all within households; a cardiovascular cause was suspected in four
      cases. CONCLUSION: These preliminary results support the feasibility of
      establishing a cohort in Benin. It would require technical and resource support.

PMID- 28498742
TI  - Contraindications and Alternatives to Nuanced Corporate Responsibility.

PMID- 28498744
TI  - Isolationist Policies Threaten Public Health.

PMID- 28498740
TI  - Powassan Virus: An Emerging Arbovirus of Public Health Concern in North America.
AB  - Powassan virus (POWV, Flaviviridae) is the only North American member of the tick
      borne encephalitis serogroup of flaviviruses. It is transmitted to small- and
      medium-sized mammals by Ixodes scapularis, Ixodes cookei, and several other
      Ixodes tick species. Humans become infected with POWV during spillover
      transmission from the natural transmission cycles. In humans, POWV is the
      causative agent of a severe neuroinvasive illness with 50% of survivors
      displaying long-term neurological sequelae. POWV was recognized as a human
      pathogen in 1958 when a young boy died of severe encephalitis in Powassan,
      Ontario, and POWV was isolated from the brain autopsy of this case. Two distinct
      genetic lineages of POWV are now recognized: POWV (lineage I) and deer tick virus
      (lineage II). Since the index case in 1958, over 100 human cases of POWV have
      been reported, with an apparent rise in disease incidence in the past 16 years.
      This recent increase in cases may represent a true emergence of POWV in regions
      where the tick vector species are prevalent, or it could represent an increase in
      POWV surveillance and diagnosis. In the past 5 years, both basic and applied
      research for POWV disease has intensified, including phylogenetic studies, field
      surveillance, case studies, and animal model development. This review provides an
      overview of POWV, including the epidemiology, transmission, clinical disease, and
      diagnosis of POWV infection. Recent research developments and future priorities
      with regard to the disease are emphasized.

PMID- 28498743
TI  - Addressing Zika in the United States: Polarization, Fragmentation, and Public
      Health.

PMID- 28498746
TI  - The Case for Politics and Public Health: 2017.

PMID- 28498745
TI  - Scientific Document Review at the Centers for Disease Control and Prevention: The
      CLEAR Approach.

PMID- 28498747
TI  - Barriers to Engaging Transgender Women in HIV Observational Research.

PMID- 28498748
TI  - Tempels et al. Respond.

PMID- 28498749
TI  - Air Mattresses Are Not Appropriate Sleep Spaces for Infants.

PMID- 28498750
TI  - Changing Demographics of Marijuana Initiation: Bad News or Good?

PMID- 28498751
TI  - Surveillance as Our Sextant.

PMID- 28498753
TI  - Evolution of Public Health Surveillance: Status and Recommendations.

PMID- 28498752
TI  - Improving Public Health Surveillance About Asian Americans, Native Hawaiians, and
      Pacific Islanders.

PMID- 28498754
TI  - More Research Is Needed to Understand the Trans Community.

PMID- 28498755
TI  - The Value of State-Based Surveillance and Surveys in the United States.

PMID- 28498756
TI  - A Public Health of Consequence: Review of the June 2017 Issue of AJPH.

PMID- 28498757
TI  - Public Health Surveillance for Communicable Diseases: From Rigid and Static to
      Flexible and Innovative.

PMID- 28498759
TI  - Social Determinants of Health: Building Wide Coalitions Around Well-Honed
      Messages.

PMID- 28498761
TI  - Zika's Long Haul: Tackling the Causes of Human Vulnerability to Mosquito-Borne
      Viruses.

PMID- 28498762
TI  - VanderWeele and Koenig Respond.

PMID- 28498763
TI  - Religion and Public Health Curriculum.

PMID- 28498764
TI  - VanderWeele and Koenig Respond.

PMID- 28498765
TI  - Courses in Religion and Public Health.

PMID- 28498767
TI  - AJPH Global News.

PMID- 28498766
TI  - Advancing the Field of Public Health Surveillance and Survey Methods.

PMID- 28498768
TI  - I Have Randomized by Clinic; Now What? Four Decades After Cornfield.

PMID- 28498769
TI  - Ying et al. Respond.

PMID- 28498772
TI  - Toward a Comprehensive Policy to Reduce Disparities in Youth Violence.

PMID- 28498770
TI  - Major Gun Death Declines in New York, California, and Texas.

PMID- 28498773
TI  - Dissemination and Implementation Research: From a Reporting Framework to
      Precision Medicine.

PMID- 28498774
TI  - A New Day Dawns for Direct-to-Consumer Marketing.

PMID- 28498776
TI  - AAV Capsid Engineering: Zooming in on the Target.

PMID- 28498775
TI  - Chalcone-based carbamates for Alzheimer's disease treatment.
AB  - AIM: Alzheimer's disease is a still untreatable multifaceted pathology, and drugs
      able to stop or reverse its progression are urgently needed. In this picture, the
      recent reformulation of the cholinergic hypothesis renewed the interest for
      acetylcholinesterase inhibitors. In this paper, a series of naturally inspired
      chalcone-based carbamates was designed to target cholinesterase enzymes and
      possibly generate fragments endowed with neuroprotective activity in situ.
      Results & methodology: All compounds presented in this study showed nanomolar
      potency for cholinesterase inhibition. Notably, fragment 11d also displayed an
      interesting neuroprotective profile. CONCLUSION: These new derivatives are able
      to simultaneously modulate different key targets involved in Alzheimer's disease,
      and could be regarded as promising starting points for the development of disease
      modifying drug candidates. [Formula: see text].

PMID- 28498777
TI  - Authors' Response to Jesse D. Riordan, Hum Gene Ther 2017;28:375-376; DOI:
      10.1089/hum.2017.045.

PMID- 28498778
TI  - Seasonal ambient particulate matter and population health outcomes among
      communities impacted by road dust in British Columbia, Canada.
AB  - : In recent years, many air quality monitoring programs have favored measurement
      of particles less than 2.5 um (PM2.5) over particles less than 10 um (PM10) in
      light of evidence that health impacts are mostly from the fine fraction. However,
      the coarse fraction (PM10-2.5) may have independent health impacts that support
      continued measurement of PM10 in some areas, such as those affected by road dust.
      The objective of this study was to evaluate the associations between different
      measures of daily PM exposure and two daily indicators of population health in
      seven communities in British Columbia, Canada, where road dust is an ongoing
      concern. The measures of exposure were PM10, PM2.5, PM10-2.5, PM2.5 adjusted for
      PM10-2.5, and PM10-2.5 adjusted for PM2.5. The indicators of population health
      were dispensations of the respiratory reliever medication salbutamol sulfate and
      nonaccidental mortality. This study followed a time-series design using Poisson
      regression over a 2003-2015 study period, with analyses stratified by three
      seasons: residential woodsmoke in winter; road dust in spring; and wildfire smoke
      in summer. A random-effects meta-analysis was conducted to establish a pooled
      estimate. Overall, an interquartile range increase in daily PM10-2.5 was
      associated with a 3.6% [1.6, 5.6] increase in nonaccidental mortality during the
      road dust season, which was reduced to 3.1% [0.8, 5.4] after adjustment for
      PM2.5. The adjusted coarse fraction had no effect on salbutamol dispensations in
      any season. However, an interquartile range increase in PM2.5 was associated with
      a 2.7% [2.0, 3.4] increase in dispensations during the wildfire season. These
      analyses suggest different impacts of different PM fractions by season, with a
      robust association between the coarse fraction and nonaccidental mortality in
      communities and periods affected by road dust. We recommend that PM10 monitoring
      networks be maintained in these communities to provide feedback for future dust
      mitigation programs. IMPLICATIONS: There was a significant association between
      daily concentrations of the coarse fraction and nonaccidental mortality during
      the road dust season, even after adjustment for the fine fraction. The acute and
      chronic health effects associated with exposure to the coarse fraction remain
      unclear, which supports the maintenance of PM10 monitoring networks to allow for
      further research in communities affected by sources such as road dust.

PMID- 28498779
TI  - Evaluation of the Education "Clinical Telemedicine/e-Health" in the Curriculum of
      Medical Students at the University of Zurich.
AB  - BACKGROUND: Digitalization and patient empowerment result in new requirements and
      challenges. In response, the module "Clinical Telemedicine/e-Health" was
      implemented by the Faculty of Medicine of Zurich in 2008. The module was
      systematically evaluated to determine if the students would benefit from this
      course. In 2011, 2015, and 2016 further evaluations were performed. METHOD: In
      2008 and 2009, students evaluated 16 statements. We calculated the combined mean
      value and medians for both evaluations. In 2011, the same evaluation was
      conducted, and the results were compared through U-test. In 2015, students were
      asked about the application and benefits of telemedicine; the answers were
      analyzed qualitatively and quantitatively. In 2016, the University of Zurich
      created an online survey which integrated three of the statements from the
      original evaluations. RESULTS: Every mean value of the combined evaluations of
      2008/2009, 2011, and 2016 achieved a score of over 4 on a 6-point scale. In 2011,
      and also again in 2016, the overall satisfaction and understanding of
      telemedicine as a supplement in traditional medical consultations increased as
      follows: 4.71 +/- 0.74 versus 4.86 +/- 0.93 versus 5.1 +/- 1.5 and, respectively,
      5.02 +/- 0.96 versus 5.25 +/- 0.81 versus 5.7 +/- 0.6. In the 2015 evaluation,
      93% of students indicated that they would use telemedicine for chronically ill
      and elderly patients. CONCLUSION: The positive assessment of the module indicates
      the successful introduction of the topics of telemedicine and e-health to medical
      students at the University of Zurich. Throughout the course, the students gained
      confidence and basic skills.

PMID- 28498780
TI  - AP and Ca2+ alternans: An inseparable couple.

PMID- 28498781
TI  - Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB
      Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth
      Factor Receptor 2-Positive Metastatic Breast Cancer.
AB  - Purpose This phase I study assessed the safety, tolerability, pharmacokinetics,
      antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan
      ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)
      positive metastatic breast cancer. Patients and Methods Pyrotinib was
      administered continuously, orally, once per day to patients who did not have
      prior exposure to tyrosine kinase inhibitors of HER2. Planned dose escalation was
      80, 160, 240, 320, 400, and 480 mg. For pharmacokinetic analysis, timed blood
      samples were collected on day 1 and day 28. Next-generation sequencing was
      performed on circulating tumor DNA and genomic DNA from tumor samples. Results
      Thirty-eight patients were enrolled. The dose-limiting toxicity was grade 3
      diarrhea, which occurred in two patients administered 480 mg of pyrotinib; thus,
      the maximum tolerated dose was 400 mg. Common pyrotinib-related adverse events
      included diarrhea (44.7% [17 of 38]), nausea (13.2% [five of 38]), oral
      ulceration (13.2% [five of 38]), asthenia (10.5% [four of 38]), and leukopenia
      (10.5% [four of 38]). The only grade 3 adverse event was diarrhea.
      Pharmacokinetic analyses indicated that pyrotinib exposure was dose dependent.
      The overall response rate was 50.0% (18 of 36), and the clinical benefit rate
      (complete response + partial response + stable disease >= 24 weeks) was 61.1% (22
      of 36). The median progression-free survival was 35.4 weeks (95% CI, 23.3 to 40.0
      weeks). The overall response rate was 83.3% (10 of 12) in trastuzumab-naive
      patients and 33.3% (eight of 24) in trastuzumab-pretreated patients. Preliminary
      results suggest that PIK3CA and TP53 mutations in circulating tumor DNA ( P =
      .013) rather than in archival tumor tissues ( P = .474) may predict the efficacy
      of pyrotinib. Conclusion Continuous once-per-day pyrotinib was well tolerated and
      demonstrated promising antitumor activity in HER2-positive patients with
      metastatic breast cancer. The maximum tolerated dose was established as 400 mg.
      Diarrhea was the dose-limiting toxicity. The promising antitumor activity and
      acceptable tolerability of pyrotinib warrant its further evaluation in a phase II
      study.

PMID- 28498783
TI  - Ultrasound Molecular Imaging: A Good Start.

PMID- 28498782
TI  - Clonal History and Genetic Predictors of Transformation Into Small-Cell
      Carcinomas From Lung Adenocarcinomas.
AB  - Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into
      small-cell lung cancer (SCLC) has been described as one of the major resistant
      mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs). However, the molecular pathogenesis is still unclear. Methods We
      investigated 21 patients with advanced EGFR-mutant LADCs that were transformed
      into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied
      for nine tumors acquired at various time points from four patients to reconstruct
      their clonal evolutionary history and to detect genetic predictors for small-cell
      transformation. The findings were validated by immunohistochemistry in 210 lung
      cancer tissues. Results We identified that EGFR TKI-resistant LADCs and SCLCs
      share a common clonal origin and undergo branched evolutionary trajectories. The
      clonal divergence of SCLC ancestors from the LADC cells occurred before the first
      EGFR TKI treatments, and the complete inactivation of both RB1 and TP53 were
      observed from the early LADC stages in sequenced tumors. We extended the findings
      by immunohistochemistry in the early-stage LADC tissues of 75 patients treated
      with EGFR TKIs; inactivation of both Rb and p53 was strikingly more frequent in
      the small-cell-transformed group than in the nontransformed group (82% v 3%; odds
      ratio, 131; 95% CI, 19.9 to 859). Among patients registered in a predefined
      cohort (n = 65), an EGFR mutant LADC that harbored completely inactivated Rb and
      p53 had a 43* greater risk of small-cell transformation (relative risk, 42.8; 95%
      CI, 5.88 to 311). Branch-specific mutational signature analysis revealed that
      apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-induced
      hypermutation was frequent in the branches toward small-cell transformation.
      Conclusion EGFR TKI-resistant SCLCs are branched out early from the LADC clones
      that harbor completely inactivated RB1 and TP53. The evaluation of RB1 and TP53
      status in EGFR TKI-treated LADCs is informative in predicting small-cell
      transformation.

PMID- 28498785
TI  - Laparoscopic Adrenalectomy for Conn's Syndrome is Beneficial to Patients and is
      Cost Effective in England.
AB  - PURPOSE: Adrenalectomy has the potential to cure or improve the control of
      hypertension in patients with primary hyperaldosteronism due to unilateral
      adrenal adenoma (Conn's syndrome). This study assesses the patients' perception
      of, and costs associated with, laparoscopic adrenalectomy for Conn's syndrome.
      MATERIALS AND METHODS: Clinical, radiological, operative, and pathological data
      were collected on patients undergoing adrenalectomy for Conn's syndrome over 8
      years period in a UK tertiary referral center. RESULTS: Thirty-eight patients
      (17M:21F, age 34-79 yrs, median 54 yrs) operated between Jan2005-Sept2012 had
      lateralization based on CT scans (n = 30) and/or MRI scans (n = 18) and confirmed
      on selective adrenal venous sampling (n = 25). Laparoscopic adrenalectomy was
      performed in all patients, with two cases requiring conversion to open operation.
      Median operative time was 105 min (range: 27-315). Costs were estimated as L19k
      for preoperative investigations, L20k for in-hospital stay, L53k for operating
      theatre use and L29k for disposable surgical instruments, with average
      L3499/patient (national tariff for adrenalectomy in 2015/2016 L3624). Follow-up
      at a mean of 30 months postoperatively using a visual analogue scale and a
      standardized questionnaire showed significantly improved quality of life (QoL)
      post-operatively. Majority of patients (85%) reported taking none or fewer anti
      hypertensive medications (median reduction of 2 antihypertensive drugs). All
      patients stated that they would definitely have the operation again in preference
      to anti-hypertensive medications and they would recommend the operation to
      friends/relatives. CONCLUSIONS: Laparoscopic adrenalectomy for Conn's syndrome
      has a positive impact on hypertension control, leads to improved QoL and its
      costs are covered in the NHS financial model.

PMID- 28498787
TI  - Spatial and temporal variability of atmospheric mercury concentrations emitted
      from a coal-fired power plant in Mexico.
AB  - : Atmospheric mercury in the environment as a result of the consumption of fossil
      fuels, such as coal used in electricity generation, has gained increased
      attention worldwide because of its toxicity, atmospheric persistence, and
      bioaccumulation. Determining or predicting the concentration of this pollutant in
      ambient air is essential for determining sensitive areas requiring health
      protection. This study investigated the spatiotemporal variability of gaseous
      elemental mercury (GEM) concentrations and its dry deposition surrounding the
      Presidente Plutarco Elias Calles (CETEPEC) coal-fired power plant, located on
      Mexico's Pacific coast. The CALPUFF dispersion model was applied on the basis of
      the daily consumption of coal during 2013 for each generating unit in the power
      plant and considering the local scale. The established 300-ng/m3 annual average
      risk factor considered by the U.S. Department of Health and Human Services (U.S.
      DHHS) and Integrated Risk Information System (IRIS) must not be exceeded to meet
      satisfactory air quality levels. An area of 65 * 60 km was evaluated, and the
      results show that the risk level for mercury vapor was not exceeded because the
      annual average concentration was 2.8 ng/m3. Although the predicted risk level was
      not exceeded, continuous monitoring studies of GEM and of particulates in the
      atmosphere, soil, and water may be necessary to identify the concentration of
      this pollutant, specifically that resulting from coal-fired power plants operated
      in environmental areas of interest in Mexico. The dry mercury deposition was low
      in the study area; according to the CALPUFF model, the annual average was 1.40E-2
      ng/m2/sec. These results represent a starting point for Mexico's government to
      implement the Minamata Convention on Mercury, which Mexico signed in 2013.
      IMPLICATIONS: The obtained concentrations of mercury from a bigger coal-fired
      plant in Mexico, through the application of the CALPUFF dispersion model by the
      mercury emissions, are below the level recommended according to the US Department
      of Health and Human Services and Integrated Risk Information System. These
      results provide evidence of important progress in the planning and installation
      to the future of monitoring mercury stations in the area of interest.

PMID- 28498784
TI  - Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM
      Clinical Trials.
AB  - Purpose To perform a critical analysis on the impact of depth of response in
      newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed
      from 609 patients who were enrolled in the GEM (Grupo Espanol de Mieloma) 2000
      and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65
      clinical trial for elderly patients with MM who had minimal residual disease
      (MRD) assessments 9 months after study enrollment. Median follow-up of the series
      was 71 months. Results Achievement of complete remission (CR) in the absence of
      MRD negativity was not associated with prolonged progression-free survival (PFS)
      and overall survival (OS) compared with near-CR or partial response (median PFS,
      27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months,
      respectively). MRD-negative status was strongly associated with prolonged PFS
      (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and
      in subgroups defined by prior transplantation, disease stage, and cytogenetics,
      with prognostic superiority of MRD negativity versus CR particularly evident in
      patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed
      higher discrimination for both PFS and OS in Cox models that included MRD (as
      opposed to CR) for response assessment. Superior MRD-negative rates after
      different induction regimens anticipated prolonged PFS. Among 34 MRD-negative
      patients with MM and a phenotypic pattern of bone marrow involvement similar to
      monoclonal gammopathy of undetermined significance at diagnosis, the probability
      of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate
      was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses
      the prognostic value of CR achievement for PFS and OS across the disease
      spectrum, regardless of the type of treatment or patient risk group. MRD
      negativity should be considered as one of the most relevant end points for
      transplant-eligible and elderly fit patients with MM.

PMID- 28498788
TI  - Nutritional status, energy expenditure, and protein oxidative stress after kidney
      transplantation.
AB  - OBJECTIVES: To evaluate the association between nutritional status, resting
      energy expenditure (REE), and protein oxidative stress in patients after kidney
      transplantation (KT). METHODOLOGY: The study evaluated 35 patients transplanted
      at the time of hospital discharge and 3 months after regarding: body composition,
      REE (by indirect calorimetry), and injury factor (IF); serum urea, creatinine,
      glucose, albumin, total protein, advanced oxidation protein products (AOPP),
      vitamin C. RESULTS: Three months after discharge, there was an improvement in
      renal function, nutritional status, and oxidative stress, with a standardization
      in the REE/kg. There was an increase in body weight, mainly in fat mass. The
      correlations showed that a greater cold ischemia time resulted in a deeper
      decline in vitamin C; a longer hospital length stay resulted in a greater
      reduction in AOPP; the higher preoperative body weight showed greater increases
      in body fat and glucose after transplantation. For decreases in REE and IF, there
      were increases in total protein. Finally, at hospital discharge there was a
      greater gain in weight, lower albumin, and total protein among individuals who
      had rejection episodes. DISCUSSION: The KT improves many of metabolic
      abnormalities, with the improvement of nutritional status, oxidative stress, and
      normalization of REE.

PMID- 28498789
TI  - Corrigendum.

PMID- 28498790
TI  - Prognostic Value of Percentage Change in Metabolic Parameters as Measured by Dual
      Time Point 18F-FDG PET/CT in Premenopausal Women with Invasive Ductal Breast
      Carcinoma.
AB  - OBJECTIVES: We retrospectively evaluated the prognostic significance of dual-time
      point (DTP) 18F-FDG positron emission tomography/computed tomography (PET/CT)
      parameters compared with clinicopathological findings in premenopausal women with
      invasive ductal breast carcinoma (IDC). MATERIALS AND METHODS: Sixty-six
      premenopausal women (mean age: 42.7 +/- 5.6, range: 29.5-51.8 years) who had
      pathologically confirmed IDC were enrolled. The maximum standardized uptake value
      (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were
      measured and used to calculate percentage changes over the DTP time interval. We
      analyzed the prognostic significance of DTP PET/CT parameters,
      clinicopathological factors of pathologic tumor diameter (pTD), axillary lymph
      node status (ANS), nuclear grade, histologic grade, and immunohistochemistry
      findings using univariate and multivariate analyses. RESULTS: Disease recurrence
      was observed in 22 patients. In univariate analysis, SUVmax > 7.39, MTV > 4.28,
      TLG > 52.38, %DeltaSUVmax > 20.44, %DeltaTLG > -13.86, pTD > 2.8 cm, positive
      ANS, estrogen receptor (ER) negativity, and triple negativity were associated
      with worse prognosis than those of opposite groups in recurrence-free survival
      (all p < 0.05). %DeltaSUVmax (>20.44, p = 0.0042), TLG (>52.38, p = 0.0002), and
      ER negativity (p = 0.0003) were independent prognostic variables after
      multivariate analysis. CONCLUSION: Percentage changes in SUVmax using DTP PET/CT
      and TLG were significant independent prognostic factors of disease recurrence
      along with ER negativity in premenopausal women with IDC.

PMID- 28498791
TI  - The influence of successive matches on match-running performance during an under
      23 international soccer tournament: The necessity of individual analysis.
AB  - This study investigated the effects of successive matches on match-running in
      elite under-23 soccer players during an international tournament. Match-running
      data was collected using a semi-automated multi-camera tracking system during an
      international under-23 tournament from all participating outfield players.
      Players who played 100% of all group stage matches were included (3 matches
      separated by 72 h, n = 44). Differences in match-running performance between
      matches were identified using a generalised linear mixed model. There were no
      clear effects for total, walking, jogging, running, high-speed running and
      sprinting distance between matches 1 and 3 (effect size (ES); -0.32 to 0.05).
      Positional analysis found that sprint distance was largely maintained from
      matches 1 to 3 across all positions. Attackers had a moderate decrease in total,
      jogging and running distance between matches 1 and 3 (ES; -0.72 to -0.66).
      Classifying players as increasers or decreasers in match-running revealed that
      match-running changes are susceptible to individual differences. Sprint
      performance appears to be maintained over successive matches regardless of
      playing position. However, reductions in other match-running categories vary
      between positions. Changes in match-running over successive matches affect
      individuals differently; thus, players should be monitored on an individual
      basis.

PMID- 28498793
TI  - Catheter-directed Intraportal Delivery of Endothelial Cell Therapy for Liver
      Regeneration: A Feasibility Study in a Large-Animal Model of Cirrhosis.
AB  - Purpose To demonstrate the feasibility of imaging-guided catheter-directed
      delivery of endothelial cell therapy in a porcine model of cirrhosis for liver
      regeneration. Materials and Methods After approval from the institutional animal
      care and use committee, autologous liver endothelial cells were grown from core
      hepatic specimens from swine. Cirrhosis was induced in swine by means of
      transcatheter infusion of ethanol and iodized oil into the hepatic artery. Three
      weeks after induction of cirrhosis, the swine were randomly assigned to receive
      autologous cell therapy (endothelial cells, n = 4) or control treatment
      (phosphate-buffered saline, n = 4) by means of imaging-guided transhepatic
      intraportal catheterization. Fluorescence-activated cell sorting analysis was
      performed on biopsy samples 1 hour after therapy. Three weeks after intraportal
      delivery of endothelial cells, the swine were euthanized and the explanted liver
      underwent quantitative pathologic examination. Statistical analysis was performed
      with an unpaired t test by using unequal variance. Results Liver endothelial
      cells were successfully isolated, cultured, and expanded from eight 20-mm, 18
      gauge hepatic core samples to 50 * 106 autologous cells per pig. Intraportal
      delivery of endothelial cell therapy or saline was technically successful in all
      eight swine, with no complications. Endothelial cells were present in the liver
      for a minimum of 1 hour after intraportal infusion. Swine treated with
      endothelial cell therapy showed mean levels of surrogate markers of hepatobiliary
      injury that were consistent with decreases in hepatic fibrosis and biliary ductal
      damage relative to the control animals, although statistical significance was not
      met in this pilot study: The mean percentage of positive pixels at Masson
      trichrome staining was 7.28% vs 5.57%, respectively (P = .20), the mean
      proliferation index with cytokeratin wide-spectrum was 2.55 vs 1.13 (P = .06),
      and the mean proliferation index with Ki67 was 7.08 vs 4.96 (P = .14). Conclusion
      The results confirm the feasibility of imaging-guided catheter-directed
      endothelial cell therapy with an intraportal technique for the treatment of
      cirrhosis in a porcine model. A trend toward decreased liver fibrosis with
      endothelial cell therapy was observed. Larger animal studies and human studies
      are necessary to confirm significance. (c) RSNA, 2017.

PMID- 28498792
TI  - Sex Differences in 1-Year Outcomes After Percutaneous Coronary Intervention in
      the Veterans Health Administration.
AB  - BACKGROUND: Advancements in percutaneous coronary intervention (PCI) for treating
      obstructive coronary artery disease have reduced major adverse events, including
      mortality. Yet, evidence as to whether women and men experience similar outcomes
      is mixed. The objective was to examine sex differences in 1-year major adverse
      cardiac outcomes for the national population of patients undergoing PCI at
      Veterans Health Administration (VA) cardiac catheterization laboratories.
      METHODS: All Veterans undergoing PCI at VA hospitals between October 1, 2007 and
      September 30, 2013 (N = 64,757; Women = 1,040) were included. Cox proportional
      hazards models compared 1-year postprocedural outcomes [rehospitalization for
      myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular
      events (MACE)] by sex. RESULTS: Women Veterans undergoing PCI were more likely to
      be younger, black, obese, and have chronic depression and less likely to have
      common cardiovascular risk factors and to have had prior cardiac events than
      Veteran men. One-year rates for women versus men were 2.1% and 2.5% for
      rehospitalization (p-value = 0.57); 3.5% and 4.9% for mortality (p-value = 0.14),
      and 5.4% and 6.9% for MACE (p-value = 0.18). There were no significant sex
      differences in any of the outcomes in Cox proportional hazards models.
      CONCLUSIONS: Despite differences in clinical risk factors at the time of PCI,
      women and men Veterans treated at VA cardiac catheterization laboratories
      experienced comparable 1-year rehospitalization for MI, mortality, and MACE post
      PCI. These results demonstrated similar 1-year post-PCI outcomes for men and
      women in a national population of patients who have more comorbidities and mental
      health issues than the general population.

PMID- 28498794
TI  - Diagnosis of Normal-Pressure Hydrocephalus: Use of Traditional Measures in the
      Era of Volumetric MR Imaging.
AB  - Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans
      index (EI) measures and to determine their role versus automated volumetric
      methods in clinical radiology. Materials and Methods Magnetic resonance (MR)
      examinations performed before surgery (within 1-5 months of the MR examination)
      in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean
      age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of
      age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control
      volunteers (n = 36) were studied. Three blinded observers independently measured
      EI and CA for each patient. Volumetric segmentation of global gray matter, white
      matter, ventricles, and hippocampi was performed by using software. These
      measures were tested by using multivariable logistic regression models to
      determine which combination of metrics is most accurate in diagnosis. Results The
      model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area
      under the curve of 0.96 in differentiating patients with NPH from patients
      without NPH (ie, Alzheimer disease and healthy control). The regression model
      that used volumetric predictors of gray matter and white matter was 94.3%
      accurate. Conclusion CA and EI may serve as a screening tool to help the
      radiologist differentiate patients with NPH from patients without NPH, which
      would allow for designation of patients for further volumetric assessment. (c)
      RSNA, 2017.

PMID- 28498795
TI  - Comparison of fetal weight distribution improved by paternal height by Spanish
      standard versus Intergrowth 21st standard.

PMID- 28498796
TI  - Interactions between cannabis and schizophrenia in humans and rodents.
AB  - In this review, we provide an overview of the relationship between cannabis use
      and the development of schizophrenia, using both animal and human studies. We
      further discuss the potential neural mechanism that may mediate the relationship
      between cannabis use and schizophrenia symptoms. We finally provide clinical
      implications and future studies that can further elucidate the relationship
      between cannabis and schizophrenia.

PMID- 28498797
TI  - NatB-mediated protein N-alpha-terminal acetylation is a potential therapeutic
      target in hepatocellular carcinoma.
AB  - The identification of new targets for systemic therapy of hepatocellular
      carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB
      catalyzes the N-alpha-terminal acetylation of 15% of the human proteome and that
      this action is necessary for proper actin cytoskeleton structure and function. In
      tumors, cytoskeletal changes influence motility, invasion, survival, cell growth
      and tumor progression, making the cytoskeleton a very attractive antitumor
      target. Here, we show that hNatB subunits are upregulated in in over 59% HCC
      tumors compared to non-tumor tissue and that this upregulation is associated with
      microscopic vascular invasion. We found that hNatB silencing blocks proliferation
      and tumor formation in HCC cell lines in association with hampered DNA synthesis
      and impaired progression through the S and the G2/M phases. Growth inhibition is
      mediated by the degradation of two hNatB substrates, tropomyosin and CDK2, which
      occurs when these proteins lack N-alpha-terminal acetylation. In addition, hNatB
      inhibition disrupts the actin cytoskeleton, focal adhesions and tight/adherens
      junctions, abrogating two proliferative signaling pathways, Hippo/YAP and ERK1/2.
      Therefore, inhibition of NatB activity represents an interesting new approach to
      treating HCC by blocking cell proliferation and disrupting actin cytoskeleton
      function.

PMID- 28498798
TI  - Differential expression of miR-195-5p in collapse of steroid-induced
      osteonecrosis of the femoral head.
AB  - BACKGROUND: Femoral head collapse is a key reference point for determining a
      treatment regimen of femoral head osteonecrosis. However, there are no effective
      preventive measures and the efficacy of hip-preserving surgery is unsatisfactory
      due to the unclear mechanism of collapse. This study aimed to identify and
      validate miRNAs differentially expressed in collapse and non-collapse areas of
      the osteonecrotic femoral head, and to predict the target genes and pathways of
      these miRNAs. RESULTS: Nine samples passed the quality control test. A total of
      2085 differentially expressed miRNAs were detected, among which 433 miRNAs showed
      differential expression in the T1 group compared to the W1 group; 344 miRNAs
      showed differential expression in the T2 group compared to the W2 group; 107
      miRNAs showed differential expression in the T3 group compared to the W3 group.
      After combining data from all three patients, 10 miRNAs showed differential
      expression in the collapse area (T1+T2+T3) compared to the non-collapse area
      (W1+W2+W3). Compared to the normal area, has-miR-195-5p showed the most
      significant downregulation. Expression results from RT-PCR revealed that the
      expression of hsa-miR-195-5p in the collapse area (T1+T2+T3) was significantly
      lower than that in the non-collapse area (W1+W2+W3) and normal area (Z1+Z2+Z3).
      157 genes were perdicted as the target gene of hsa-miR-195-5p. MATERIALS AND
      METHODS: Femoral heads of three patients (2 males and 1 female) treated by total
      hip arthroplasty surgery for steroid-induced femoral head osteonecrosis were
      selected based on inclusion and exclusion criteria. Bone tissue samples were
      obtained from the collapse area (T), non-collapse area (W), and normal area (Z)
      according to the anatomical structure of osteonecrotic femoral heads. Total RNA
      was extracted from the samples and the microarray chip was scanned. miRNAs
      showing differential expressions of more than 1.5-fold were selected and was
      validated by RT-PCR. TargetScan, mirBase and miRanda bioinformatics software was
      used to predict target genes and identify possible pathways involving these
      genes. CONCLUSIONS: miR-195-5p showed the most significant difference in the
      collapse area of osteonecrotic femoral heads, suggesting that collapse may be
      related to the downregulation of miR-195-5p.

PMID- 28498799
TI  - Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via
      the Nrf2/NF-kappaB/P53 signaling pathway in rats.
AB  - Mercury exposure is a common cause of metal poisoning which is biotransformed to
      highly toxic metabolites thus eliciting biochemical alterations and oxidative
      stress. Luteolin, a phenolic compound found in many natural products, has
      multiple biological functions. Our study was aimed to explore the biological
      effects of luteolin in a liver injury model induced in rats by mercuric chloride
      (HgCl2). Criteria for injury included liver enzyme, glutathione and
      malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and
      reactive oxygen species levels. The results showed that luteolin protected
      against HgCl2-induced liver injury. Luteolin increased total nuclear factor
      erythroid-2-related factor 2 (Nrf2) levels in the presence of HgCl2. Upregulation
      of its downstream factors, heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1,
      was also observed. This suggested that protection by luteolin against HgCl2
      induced liver injury involved Nrf2 pathway activation. Luteolin also decreased
      expression of nuclear factor-kappaB (NF-kappaB) and P53. HgCl2 exposure led to
      increased Bcl-associated X protein (Bax), and decreased Bcl-2-related protein
      long form of Bcl-x (Bcl-xL) and B-cell leukemia/lymphoma-2 (Bcl-2) expression,
      leading to an increased Bax/Bcl-2 ratio. Taken together, our data suggested that
      decreasing oxidative stress is a protective mechanism of luteolin against
      development of HgCl2-induced liver injury, through the Nrf2/NF-kappaB/P53
      signaling pathway in rats.

PMID- 28498800
TI  - Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic
      cancer growth in an orthotopic mouse model.
AB  - To obtain improved efficacy against pancreatic cancer, we investigated the
      efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric
      patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing
      polymeric patch was produced by 3D printing. After application of the patch, it
      released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer
      growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was
      performed longitudinally. The drug patch delivered a 30.2 times higher level of 5
      FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels
      were accumulated within one week by the patch. Four groups were compared for
      efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU
      loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p.
      once a week (1.2 mg), three times (Group IV). The tumor growth rate was
      significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022
      at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died
      of drug toxicity within two weeks after injection. Group II showed more effective
      suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day
      21). Histological analysis showed extensive apoptosis in the TUNEL assay and by
      Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase
      3 in Group II. No significant changes were found hematologically and
      histologically in the liver, kidney and spleen in Groups I, II, IV but were found
      in Group III.

PMID- 28498802
TI  - Sales for anti-angiogenic drugs.

PMID- 28498803
TI  - Differentially expressed proteins in glioblastoma multiforme identified with a
      nanobody-based anti-proteome approach and confirmed by OncoFinder as possible
      tumor-class predictive biomarker candidates.
AB  - Glioblastoma multiforme is the most frequent primary malignancy of the central
      nervous system. Despite remarkable progress towards an understanding of tumor
      biology, there is no efficient treatment and patient outcome remains poor. Here,
      we present a unique anti-proteomic approach for selection of nanobodies specific
      for overexpressed glioblastoma proteins. A phage-displayed nanobody library was
      enriched in protein extracts from NCH644 and NCH421K glioblastoma cell lines.
      Differential ELISA screenings revealed seven nanobodies that target the following
      antigens: the ACTB/NUCL complex, VIM, NAP1L1, TUFM, DPYSL2, CRMP1, and ALYREF.
      Western blots showed highest protein up-regulation for ALYREF, CRMP1, and VIM.
      Moreover, bioinformatic analysis with the OncoFinder software against the
      complete "Cancer Genome Atlas" brain tumor gene expression dataset suggests the
      involvement of different proteins in the WNT and ATM pathways, and in Aurora B,
      Sem3A, and E-cadherin signaling. We demonstrate the potential use of NAP1L1,
      NUCL, CRMP1, ACTB, and VIM for differentiation between glioblastoma and lower
      grade gliomas, with DPYSL2 as a promising "glioma versus reference" biomarker. A
      small scale validation study confirmed significant changes in mRNA expression
      levels of VIM, DPYSL2, ACTB and TRIM28. This work helps to fill the information
      gap in this field by defining novel differences in biochemical profiles between
      gliomas and reference samples. Thus, selected genes can be used to distinguish
      glioblastoma from lower grade gliomas, and from reference samples. These findings
      should be valuable for glioblastoma patients once they are validated on a larger
      sample size.

PMID- 28498804
TI  - Increased S100A15 expression and decreased DNA methylation of its gene promoter
      are involved in high metastasis potential and poor outcome of lung
      adenocarcinoma.
AB  - PURPOSE: This study aims to determine the functional role of S100A15 and its
      promoter DNA methylation patterns in lung cancer progression. EXPERIMENTAL
      DESIGN: We analyzed 178 formalin-fixed paraffin embedded specimens from lung
      cancer patients, including 24 early stage and 91 advanced stage adenocarcinoma.
      S100A15 protein expression was evaluated by immunohistochemistry stain, and its
      DNA methylation levels were measured by pyrosequencing. RESULTS: S100A15 nuclear
      staining was increased in lung adenocarcinoma patients with distant metastasis
      versus those without distant metastasis. There was reduced one/three-year overall
      survival in adenocarcinoma patients receiving first line target therapy and
      harboring high nuclear expressions of S100A15. Both DNA methylation levels over 
      423 and -248 CpG sites of the S100A15 gene promoter were decreased in
      adenocarcinoma patients with distant metastasis, and the former was associated
      with lower one-year overall survival. The highly invasive CL1-5 cell lines
      display decreased DNA methylation over -412/-248/-56 CpG sites of the S100A15
      gene promoter and increased S100A15 gene/protein expressions as compared with the
      less invasive CL1-0 cell lines. Knockdown of S100A15 in CL1-5 cell line inhibited
      cell proliferation, migration, and invasion, while over-expression of S100A15 in
      CL1-0 cell line promoted cell proliferation, migration, and invasion. RNA
      sequencing analysis revealed potential biological effects of S100A15 over
      expression and knock-down with CTNNB1, ZEB1, CDC42, HSP90AA1, BST2, and PCNA
      being the pivotal down-stream mediators. CONCLUSIONS: Increased S100A15
      expression and decreased DNA methylation of its gene promoter region were
      associated with high metastasis potential and poor outcome in lung
      adenocarcinoma, probably through triggering CTNNB1 -centered pathways.

PMID- 28498805
TI  - FOXM1 predicts overall and disease specific survival in muscle-invasive
      urothelial carcinoma and presents a differential expression between bladder
      cancer subtypes.
AB  - Forkhead box M1 (FOXM1) is a late cell cycle gene that plays a crucial role in
      carcinogenesis and chemotherapeutic drug resistance. In this study, the impact of
      FOXM1 expression on patient outcome was investigated for the first time in
      formalin fixed and paraffin embedded (FFPE) samples of chemotherapy naive muscle
      invasive bladder cancer (MIBC) patients. Expression analyses were performed on
      the Mannheim cohort (n=84) and validated on the independent Chungbuk cohort
      (n=61). In a Cox' proportional hazards model, a distinct FOXM1 expression cut-off
      dividing both cohorts in a 'high-risk' and 'low-risk' group has been determined.
      Multivariate analyses showed that FOXM1 is an independent risk factor for outcome
      prediction superior to the TNM system. The FOXM1 'high-risk' group had a 4- to 7
      fold increased risk of death (p<0.03) and presented further an overexpression of
      MKI67. Recent studies showed that MIBCs can be subclassified in breast cancer
      like subtypes: basal, luminal and p53-like. Here we demonstrated that FOXM1 was
      differentially expressed between MIBC subtypes concordant to its subtype specific
      expression in breast cancer. Since the proto-oncogene FOXM1 is known to play an
      important role in cisplatin resistance and to be a promising drug target, this
      study supports FOXM1 as a crucial biomarker in the personalization of MIBC
      therapy and urges prospective translational studies.

PMID- 28498806
TI  - Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth.
AB  - Expression of MHC class II pathway proteins in ovarian cancer correlates with
      prolonged survival. Murine and human ovarian cancer cells were treated with
      epigenetic modulators - histone deacetylase inhibitors and a DNA
      methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway
      were evaluated by qPCR and flow cytometry. Treatment with entinostat and
      azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2
      Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment
      with either agent. A dose dependent response in mRNA and protein expression was
      seen with entinostat. Combination treatment showed higher MHC II protein
      expression than with single agent treatment. In patient derived xenografts,
      CIITA, CD74, and MHC II mRNA transcripts were significantly increased after
      combination treatment. Expression of MHC II on ovarian tumors in MISIIR-Tag mice
      was increased with both agents relative to control. Combination treatment
      significantly reduced ID8 tumor growth in immune-competent mice. Epigenetic
      treatment increases expression of MHC II on ovarian cancer cells and impedes
      tumor growth. This approach warrants further study in ovarian cancer patients.

PMID- 28498807
TI  - Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin
      resistance in colorectal cancer cells.
AB  - Clinical treatment for colorectal cancer (CRC) thus far encounters a huge
      challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in
      aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney
      type glutaminase (GLS1) are proposed to carry important implications in
      colorectal carcinogenesis and drug-resistance. This study aimed to explore the
      possible association of oxaliplatin-resistance with aerobic
      glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1
      expression was quantified by polymerase chain reaction (PCR) and Western blot
      techniques in CRC cell lines. The abilities of cell formation, kinetics,
      migration, invasion, survival and apoptosis, as well as permeability glycoprotein
      (Pgp) expression were inspected before and after knocking-down PKM2/GLS1
      expression. In addition, the influence of knocking-down PKM2/GLS1 expression was
      evaluated in vivo. Differentiated PKM2 and GLS1 expression in both THC8307 and
      THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1
      can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate
      Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell
      line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors,
      reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell
      apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly
      inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken
      together, the present findings enriched our knowledge by demonstrating a
      significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We
      further propose that knockdown of PKM2/GLS1 expression may constitute a novel
      therapeutic strategy toward effective treatment for CRC.

PMID- 28498808
TI  - Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses
      dedifferentiated papillary thyroid cancer cells.
AB  - Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive
      growth, recurrence, distant metastasis, and resistance to radioactive iodine
      (RAI) therapy. DePTC is also accompanied by poor prognosis and high early
      mortality. Nevertheless, most DePTC cells show intact p53 downstream
      functionality. In cells with wild-type p53, the murine double minute2 (MDM2)
      protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53
      interaction restores p53 activity and leads to cell cycle arrest and apoptosis.
      Restoring p53 function by inhibiting its interaction with p53 suppressors such as
      MDM2 is thus a promising therapeutic strategy for the treatment of DePTC. The
      novel MDM2-p53 interaction antagonist APG115 is an analogue of SAR405838, and is
      being tested in a phase I clinical trial. In this study, we evaluated the
      efficacy of APG115 as a single-agent to treat DePTC. APG115 diminished the
      viability of p53 wild-type DePTC cells and induced cell cycle arrest and
      apoptosis. In a human xenograft mouse model, APG115 elicited robust tumor
      regression and cell apoptosis. These data demonstrate that further research is
      warranted to determine whether APG115 can be used to effectively treat DePTC
      patients.

PMID- 28498809
TI  - Follistatin-like protein 1 promotes inflammatory reactions in nucleus pulposus
      cells by interacting with the MAPK and NFkappaB signaling pathways.
AB  - OBJECTIVE: Follistatin-like protein 1 (FSTL1) is a well-known mediator of
      inflammation. Intervertebral disc disease is an inflammatory disorder. Here, we
      investigated the role of FSTL1 in the intervertebral discs inflammation. METHODS:
      Expression of FSTL1 in nucleus pulposus tissues from rats and human was
      determined by immunohistochemistry staining and western blot analysis. The
      expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin1-beta
      (IL-1beta) and matrix metalloproteinase 13 (MMP-13) in human and rat nucleus
      pulposus tissues were measured by immunohistochemistry staining. The mitogen
      activated protein kinase (MAPK) and nuclear factor-kappa B (NFkappaB) signaling
      pathways were detected by western blotting. RESULTS: FSTL1 serum levels were
      significantly increased in lumbar disc herniation patients and had a positive
      correlation with Visual Analogue Scores. Additionally, FSTL1 expression was
      significantly increased in extrusion group compared with protrusion and control
      groups. Furthermore, FSTL1 expression was significantly increased in
      intervertebral disc degeneration models of rats. Immunohistochemistry staining
      demonstrated that the levels of TNF-alpha, IL-1beta and MMP-13 were increased in
      the pathogenesis of intervertebral disc disease. Recombinant human FSTL1
      significantly increased the production of proinflammatory cytokines in vitro. In
      addition, FSTL1 promoted inflammation by activating c-Jun N-terminal kinase
      (JNK), extracellular regulated protein kinases 1/2(ERK1/2) and NFkappaB
      signaling. CONCLUSIONS: These data imply that FSTL1 expression was increased in
      the pathogenesis of intervertebral disc disease. Importantly, FSTL1 promoted
      inflammatory catabolism in the nucleus pulposus by activating JNK, ERK 1/2/MAPK
      and NFkappaB signaling.

PMID- 28498811
TI  - The generation and functional characterization of induced pluripotent stem cells
      from human intervertebral disc nucleus pulposus cells.
AB  - Disc degenerative disease (DDD) is believed to originate in the nucleus pulposus
      (NP) region therefore, it is important to obtain a greater number of active NP
      cells for the study and therapy of DDD. Human induced pluripotent stem cells
      (iPSCs) are a powerful tool for modeling the development of DDD in humans, and
      have the potential to be applied in regenerative medicine. NP cells were isolated
      from DDD patients following our improved method, and then the primary NP cells
      were reprogramed into iPSCs with Sendai virus vectors encoding 4 factors.
      Successful reprogramming of iPSCs was verified by the expression of surface
      markers and presence of teratoma. Differentiation of iPSCs into NP-like cells was
      performed in a culture plate or in hydrogel, whereby skin fibroblast derived
      iPSCs were used as a control. Results demonstrated that iPSCs derived from NP
      cells displayed a normal karyotype, expressed pluripotency markers, and formed
      teratoma in nude mice. NP induction of iPSCs resulted in the expression of NP
      cell specific matrix proteins and related genes. Non-induced NP derived-iPSCs
      also showed some NP-like phenotype. Furthermore, NP-derived iPSCs differentiate
      much better in hydrogel than that in a culture plate. This is a novel method for
      the generation of iPSCs from NP cells of DDD patients, and we have successfully
      differentiated these iPSCs into NP-like cells in hydrogel. This method provides a
      novel treatment of DDD by using patient-specific NP cells in a relatively simple
      and straightforward manner.

PMID- 28498810
TI  - The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis.
AB  - Increased glycolysis is one of the hallmarks of cancer. The abnormal expression
      of glucose transporter 1 (GLUT1) was reported to be associated with resistance to
      current therapy and poor prognosis. Numerous studies have investigated the
      correlation between GLUT1 expression and prognosis in cancers, but the
      conclusions are still controversial. Here, we conducted a meta-analysis to
      explore the association between GLUT1 and survival in human cancers. PubMed,
      Springer, Medline, and Cochrane Library were searched carefully to identify
      eligible studies evaluating prognostic value of GLUT1 in cancers. Twenty-seven
      studies with 4079 patients were included in the present study. Our pooled results
      identified that increased expression of GLUT1 was associated with unfavorable
      overall survival (HR = 1.780, 95% CI = 1.574-.013, p < 0.001)) and poorer disease
      free survival (HR = 1.95, 95% CI = 1.229-3.095, p = 0.003). Furthermore,
      overexpression of GLUT1 linked with poor differentiated tumors (RR = 1.380, 95%
      CI = 1.086-1.755, p = 0.009; I2 = 72.0%, p < 0.001), positive lymph node
      metastasis (RR = 1.395, 95% CI = 1.082-1.799, p = 0.010; I2 = 70.8%, p = 0.002)
      and larger tumor size (RR = 1.405, 95% CI = 1.231-1.603, p < 0.001; I2 = 37.3%, p
      = 0.093). This systematic review and meta-analysis indicated that the GLUT1 may
      serve as an ideal prognostic biomarker in various cancers.

PMID- 28498812
TI  - Structure based discovery of clomifene as a potent inhibitor of cancer-associated
      mutant IDH1.
AB  - Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic
      acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of
      acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by
      virtual screening method, which can selectively suppress mutant enzyme activities
      in vitro and in vivo with a dose-dependent manner. The molecular docking
      indicated that clomifene occupied the allosteric site of the mutant IDH1.
      Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a
      non-competitive manner. Moreover, knockdown of mutant IDH1 in HT1080 cells
      decreased the sensitivity to clomifene. In vivo studies indicated that clomifene
      significantly suppressed the tumor growth of HT1080-bearing CB-17/Icr-scid mice
      with oral administration of 100 mg/kg and 50 mg/kg per day. In short, our
      findings highlight clomifene may have clinical potential in tumor therapies as a
      safe and effective inhibitor of mutant IDH1.

PMID- 28498813
TI  - Microwave ablation combined with attenuated Salmonella typhimurium for treating
      hepatocellular carcinoma in a rat model.
AB  - We aim to investigate the safety and efficacy of microwave ablation (MWA)
      combined with attenuated Salmonella typhimurium strain VNP20009 in treating
      hepatocellular carcinoma. Portions of tumor tissues were orthotopically implanted
      in the livers of 40 male rats weighed 150~200 g to establish tumor models. Three
      weeks later, the rats were randomly divided into four groups: (A) MWA plus
      VNP20009 group; (B) MWA group; (C) VNP20009 group; and (D) control group.
      Incomplete MWA was performed (20~30 W, 1~2 min) after the hepatic carcinoma was
      properly exposed. VNP20009 (about 1*107 cfu) was directly injected into the tumor
      immediately. MRI scans were performed to assess the tumor responses 7 and 14 days
      later, respectively. Micro CT was used to observe the lung metastases. After the
      animals were sacrificed or died, the tumors were cut off for the purpose of
      pathological and immunohistochemical analyses. The results showed that the mean
      tumor volumes of MWA plus VNP20009 group on the 7th and 14th day post treatment
      were obviously smaller than those of other groups (P < 0.05). Lung metastases
      rates were 20%, 60%, 30% and 100% in MWA plus VNP20009 group, MWA group, VNP20009
      group and control group, respectively. The median survival of the rats in MWA
      plus VNP20009 group was distinctly longer than those in other groups (P < 0.05).
      In summary, MWA combined with VNP20009 produced better effects than MWA or
      VNP20009 alone in treating hepatic carcinoma. This strategy might have potential
      ability to decrease lung metastases and prolong the overall survival.

PMID- 28498814
TI  - Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma
      cells via inhibition of glycolysis and represses tumor growth in mice.
AB  - Methyl jasmonate has recently been found to have anti-cancer activity. Methyl
      jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a
      reduction in mitochondrial transmembrane potential that led to the release of
      cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis.
      Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered
      oxidative phosphorylation and led to cell necrosis. The results were applied to
      the in vivo treatment of nude mice with a satisfactory effect. Collectively, our
      results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors
      due to its mechanism in cancer cells compared to that in normal cells: The major
      function is to inhibit glycolysis instead of changing aerobic metabolism.

PMID- 28498815
TI  - The optimization of cell therapy by combinational application with apicidin
      treated mesenchymal stem cells after myocardial infarction.
AB  - Although mesenchymal stem cells (MSC) have been shown to be safe in preclinical
      studies of cardiovascular disease, multiple meta-analyses have debated whether
      functional improvement is significant or not. The cardiac differentiation from
      MSC is achievable using cardiogenic factors, however, the high cost and long
      culture period may limit the applications. Here, we developed a novel method to
      optimize the therapeutic outcome for myocardial infarction (MI). Treatment of MSC
      with apicidin, a histone deacetylase inhibitor, dramatically increased the
      expressions of cardiac markers such as GATA4, Nkx2.5, and cardiac troponin I
      (cTnI). In AC/MSC, stemness-related genes and yes-associated protein (YAP), a
      potent oncogene that drives cell proliferation, were significantly suppressed.
      Furthermore apicidin treatment or YAP knockdown downregulated miR-130a expression
      followed by induction of cardiac markers in MSC. In the comparison study, we
      found that both cardiac gene induction and angiogenesis were most prominent in
      the mixture of non-treated MSC and AC/MSC (Mix). Using mouse MI model, we show
      that application of Mix was strongly associated with cardiac differentiation of
      injected MSC and improved cardiac performance. Our results suggest that
      suppression of YAP/miR-130a shifts MSC cell fate toward cardiac lineage and
      identify apicidin as a potential pharmacological target for therapeutic
      development.

PMID- 28498820
TI  - Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is
      mediated via NPC1 and LDL-R.
AB  - Tuberous sclerosis complex (TSC) is a multisystem disease associated with
      hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated
      processes is not fully understood. We report here that inhibition of lysosomal
      function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2
      deficient cells. This TSC2-dependent transcriptional signature is associated with
      increased accumulation and intracellular levels of both total cholesterol and
      cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake
      pathway together with inhibition of de novo cholesterol synthesis allows survival
      of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of
      TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL
      R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of
      lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and
      cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the
      TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and
      pointing toward the translational potential of these pathways for the therapy of
      TSC.

PMID- 28498823
TI  - Enhancing the thermal dissipation of a light-converting composite for quantum dot
      based white light-emitting diodes through electrospinning nanofibers.
AB  - Quantum dots (QDs) have been developed as one of the most promising light
      converting materials for white light-emitting diodes (LEDs). In current QD-based
      LED packaging structures, composites of QDs and polymers are used as light
      converting layers. However, the ultralow thermal conductivity of such composites
      seriously hinders the dissipation of QD-generating heat. In this paper, we
      demonstrate a method to enhance the thermal dissipation of QD-polymer composites
      through electrospinning polymer nanofibers. QD-polymer films embedded by
      electrospun nanofibers were prepared. Benefitting from aligned polymer chains in
      the electrospun nanofibers, the through-panel and in-panel thermal conductivities
      of the proposed QD-polymer film increased by 39.9% and 423.1%, respectively,
      compared to traditional QD-polymer film. The proposed and traditional QD-polymer
      films were both packaged on chip on board (CoB) LEDs for experimental comparison.
      Compared to traditional QD-polymer film, the luminous flux and luminous
      efficiency of the LEDs were increased by up to 51.8% and 42.9% by the proposed QD
      polymer film under a current of 800 mA, respectively. With an increase in the
      driving current from 20-800 mA, the correlated color temperature (CCT) variation
      decreased by 72.7%. The maximum temperatures in the QD-polymer films were reduced
      from 419 K-411 K under a driving current of 200 mA.

PMID- 28498822
TI  - Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation
      of human colon cancer cells.
AB  - Human colon cancers express higher levels of NADPH oxidase 1 [NOX1] than adjacent
      normal epithelium. It has been suggested that reactive oxygen species [ROS]
      derived from NOX1 contribute to DNA damage and neoplastic transformation in the
      colon, particularly during chronic inflammatory stress. However, the mechanism(s)
      underlying increased NOX1 expression in malignant tumors or chronic inflammatory
      states involving the intestine are poorly characterized. We examined the effects
      of two pro-inflammatory cytokines, IL-4 and IL-13, on the regulation of NOX1.
      NOX1 expression was increased 4- to 5-fold in a time- and concentration-dependent
      manner by both cytokines in human colon cancer cell lines when a functional Type
      II IL-4 receptor was present. Increased NOX1 transcription following IL-4/IL-13
      exposure was mediated by JAK1/STAT6 signaling, was associated with a ROS-related
      inhibition of protein tyrosine phosphatase activity, and was dependent upon
      activation and specific binding of GATA3 to the NOX1 promoter. NOX1-mediated ROS
      production increased cell cycle progression through S-phase leading to a
      significant increase in cellular proliferation. Evaluation of twenty pairs of
      surgically-resected colon cancers and their associated uninvolved adjacent
      colonic epithelium demonstrated a significant increase in the active form of
      NOX1, NOX1-L, in tumors compared to normal tissues, and a significant correlation
      between the expression levels of NOX1 and the Type II IL-4 receptor in tumor and
      the uninvolved colon. These studies imply that NOX1 expression, mediated by IL
      4/IL-13, could contribute to an oxidant milieu capable of supporting the
      initiation or progression of colonic cancer, suggesting a role for NOX1 as a
      therapeutic target.

PMID- 28498824
TI  - Sublimation-assisted graphene transfer technique based on small polyaromatic
      hydrocarbons.
AB  - Advances in the chemical vapor deposition (CVD) growth of graphene have made this
      material a very attractive candidate for a number of applications including
      transparent conductors, electronics, optoeletronics, biomedical devices and
      energy storage. The CVD method requires transfer of graphene on a desired
      substrate and this is most commonly accomplished with polymers. The removal of
      polymer carriers is achieved with organic solvents or thermal treatment which
      makes this approach inappropriate for application to plastic thin films such as
      polyethylene terephthalate substrates. An ultraclean graphene transfer method
      under mild conditions is highly desired. In this article, we report a naphthalene
      assisted graphene transfer technique which provides a reliable route to residue
      free transfer of graphene to both hard and flexible substrates. The quality of
      the transferred graphene was characterized with atomic force microscopy, scanning
      electron microscopy, and Raman spectroscopy. Field effect transistors, based on
      the naphthalene-transfered graphene, were fabricated and characterized. This work
      has the potential to broaden the applications of CVD graphene in fields where
      ultraclean graphene and mild graphene transfer conditions are required.

PMID- 28498825
TI  - Direct evidence of barrier inhomogeneities at metal/AlGaN/GaN interfaces using
      nanoscopic electrical characterizations.
AB  - The existence of barrier inhomogeneities at metal-semiconductor interfaces is
      believed to be one of the reasons for the non-ideal behaviour of Schottky
      contacts. In general, barrier inhomogeneities are modelled using a Gaussian
      distribution of barrier heights of nanoscale patches having low and high barrier
      heights, and the standard deviation of this distribution roughly estimates the
      level of barrier inhomogeneities. In the present work, we provide direct
      experimental evidence of barrier inhomogeneities by performing electrical
      characterizations on individual nanoscale patches and, further, obtaining the
      magnitude of these inhomogeneities. Localized current-voltage measurements on
      individual nanoscale patches were performed using conducting atomic force
      microscopy (CAFM) whereas surface potential variations on nanoscale dimensions
      were investigated using Kelvin probe force microscopy (KPFM) measurements. The
      CAFM measurements revealed the distribution of barrier heights, which is
      attributed to surface potential variations at nanoscale dimensions, as obtained
      from KPFM measurements. The present work is an effort to provide direct evidence
      of barrier inhomogeneities, finding their origin and magnitude by combining CAFM
      and KPFM techniques and correlating their findings.

PMID- 28498826
TI  - Divergent Influences of Cardiovascular Disease Risk Factor Domains on Cognition
      and Gray and White Matter Morphology.
AB  - OBJECTIVE: Hypertension, diabetes, dyslipidemia, and obesity are associated with
      preclinical alterations in cognition and brain structure; however, this often
      comes from studies of comprehensive risk scores or single isolated factors. We
      examined associations of empirically derived cardiovascular disease risk factor
      domains with cognition and brain structure. METHODS: A total of 124 adults (age,
      59.8 [13.1] years; 41% African American; 50% women) underwent neuropsychological
      and cardiovascular assessments and structural magnetic resonance imaging.
      Principal component analysis of nine cardiovascular disease risk factors resulted
      in a four-component solution representing 1, cholesterol; 2, glucose
      dysregulation; 3, metabolic dysregulation; and 4, blood pressure. Separate linear
      regression models for learning, memory, executive functioning, and
      attention/information processing were performed, with all components entered at
      once, adjusting for age, sex, and education. MRI analyses included whole-brain
      cortical thickness and tract-based fractional anisotropy adjusted for age and
      sex. RESULTS: Higher blood pressure was associated with poorer learning (B = 
      0.19; p = .019), memory (B = -0.22; p = .005), and executive functioning
      performance (B = -0.14; p = .031), and lower cortical thickness within the right
      lateral occipital lobe. Elevated glucose dysregulation was associated with poorer
      attention/information processing performance (B = -0.21; p = .006) and lower
      fractional anisotropy in the right inferior and bilateral superior longitudinal
      fasciculi. Cholesterol was associated with higher cortical thickness within left
      caudal middle frontal cortex. Metabolic dysfunction was positively associated
      with right superior parietal lobe, left inferior parietal lobe, and left
      precuneus cortical thickness. CONCLUSIONS: Cardiovascular domains were associated
      with distinct cognitive, gray, and white matter alterations and distinct age
      groups. Future longitudinal studies may assist in identifying vulnerability
      profiles that may be most important for individuals with multiple cardiovascular
      disease risk factors.

PMID- 28498827
TI  - The Accuracy of the Spot Sign and the Blend Sign for Predicting Hematoma
      Expansion in Patients with Spontaneous Intracerebral Hemorrhage.
AB  - BACKGROUND Hematoma expansion is associated with poor outcome in intracerebral
      hemorrhage (ICH) patients. The spot sign and the blend sign are reliable tools
      for predicting hematoma expansion in ICH patients. The aim of this study was to
      compare the accuracy of the two signs in the prediction of hematoma expansion.
      MATERIAL AND METHODS Patients with spontaneous ICH were screened for the presence
      of the computed tomography angiography (CTA) spot sign and the non-contrast CT
      (NCCT) blend sign within 6 hours after onset of symptoms. The sensitivity,
      specificity, and positive and negative predictive values of the spot sign and the
      blend sign in predicting hematoma expansion were calculated. The accuracy of the
      spot sign and the blend sign in predicting hematoma expansion was analyzed by
      receiver-operator analysis. RESULTS A total of 115 patients were enrolled in this
      study. The spot sign was observed in 25 (21.74%) patients, whereas the blend sign
      was observed in 22 (19.13%) patients. Of the 28 patients with hematoma expansion,
      the CTA spot sign was found on admission CT scans in 16 (57.14%) and the NCCT
      blend sign in 12 (42.86%), respectively. The sensitivity, specificity, positive
      predictive value, and negative predictive value of the spot sign for predicting
      hematoma expansion were 57.14%, 89.66%, 64.00%, and 86.67%, respectively. In
      contrast, the sensitivity, specificity, positive predictive value, and negative
      predictive value of the blend sign were 42.86%, 88.51%, 54.55%, and 82.80%,
      respectively. The area under the curve (AUC) of the spot sign was 0.734, which
      was higher than that of the blend sign (0.657). CONCLUSIONS Both the spot sign
      and the blend sign seemed to be good predictors for hematoma expansion, and the
      spot sign appeared to have better predictive accuracy.

PMID- 28498828
TI  - KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in
      mice.
AB  - The proper regulation of spermatogenesis is crucial to ensure the continued
      production of sperm and fertility. Here, we investigated the function of the
      H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult
      mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to
      fewer spermatogonia and germ cell loss before 3 weeks of age. These results
      demonstrate that KDM1A is required for spermatogonial differentiation, as well as
      germ cell survival, in the developing testis. In addition, inducible deletion of
      Kdm1a in the adult testis results in the abnormal accumulation of meiotic
      spermatocytes, as well as apoptosis and progressive germ cell loss. These results
      demonstrate that KDM1A is also required during adult spermatogenesis.
      Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained
      in differentiating germ cells. This requirement for KDM1A is similar to what has
      been observed in other stem cell populations, suggesting a common function. Taken
      together, we propose that KDM1A is a key regulator of spermatogenesis and germ
      cell maintenance in the mouse.

PMID- 28498830
TI  - The influence of the Great East Japan earthquake on microscopic polyangiitis: A
      retrospective observational study.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis is
      triggered by environmental factors, including silica dust exposure. Repeated
      tsunami waves brought a large volume of silica-containing sludge inland after the
      Great East Japan earthquake in 2011. We aimed to determine if the serious
      disaster influenced the clinical features of the microscopic polyangiitis.
      METHODS: This is an observational retrospective study conducted in a single
      institute. A total of 43 patients were included based on the CHCC2012 criteria
      for microscopic polyangiitis from 2007 to 2015. We used the Poisson regression
      model to determine the incidence of microscopic polyangiitis within the annual
      population of the medical district. The participants were selected during a 3
      year period from before (N = 13) to after the disaster (N = 20). The differences
      of parameters and the overall survival between the groups were analyzed. RESULTS:
      The incidence of microscopic polyangiitis increased after the disaster (lambda =
      17.4/million/year [95%CI: 7.66-39.6] before the disaster and lambda =
      33.1/million/year [17.7-61.7] after the disaster, P = 0.044). A high Birmingham
      Activity Score was associated with a high incidence of microscopic polyangiitis
      after the disaster. The overall survival of the patients with microscopic
      polyangiitis declined significantly after the disaster. CONCLUSIONS: The Great
      East Japan earthquake influenced the development of the microscopic polyangiitis
      in our restricted area. The patients who developed after the disaster had severe
      symptoms and a high mortality rate.

PMID- 28498829
TI  - Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian
      patients.
AB  - INTRODUCTION: The association between the BTD genotype and biochemical phenotype
      [profound biotinidase deficiency (BD), partial BD or heterozygous activity] is
      not always consistent. This study aimed to investigate the genotype-biochemical
      phenotype association in patients with low biotinidase activity. METHODS: All
      exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian
      individuals who exhibited low biotinidase activity. For each patient, the
      expected biochemical phenotype based on the known genotype was compared with the
      observed biochemical phenotype. Additional non-genetic factors that could affect
      the biotinidase activity were also analysed. RESULTS: Most individuals were
      identified by neonatal screening (n = 66/72). When consecutive results for the
      same patient were compared, age, prematurity and neonatal jaundice appeared to
      affect the level of biotinidase activity. The biochemical phenotype at the time
      of the second blood collection changed in 11/22 patients compared to results from
      the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G
      (p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented
      different biochemical phenotypes. The expected and observed biochemical
      phenotypes agreed in 68.5% of cases (concordant patients). The non-coding
      variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17
      discordant patients. In addition, c.-183G>A and c.-514C>T were also present in
      10/37 concordant patients. CONCLUSIONS: The variants found in the promoter region
      do not appear to have a strong impact on biotinidase activity. Since there is a
      disparity between the BTD genotype and biochemical phenotype, and biotinidase
      activity may be affected by both genetic and non-genetic factors, we suggest that
      the diagnosis of BD should be based on more than one measurement of plasma
      biotinidase activity. DNA analysis can be of additional relevance to
      differentiate between partial BD and heterozygosity.

PMID- 28498831
TI  - Dynamics of analyst forecasts and emergence of complexity: Role of information
      disparity.
AB  - We report complex phenomena arising among financial analysts, who gather
      information and generate investment advice, and elucidate them with the help of a
      theoretical model. Understanding how analysts form their forecasts is important
      in better understanding the financial market. Carrying out big-data analysis of
      the analyst forecast data from I/B/E/S for nearly thirty years, we find skew
      distributions as evidence for emergence of complexity, and show how information
      asymmetry or disparity affects financial analysts' forming their forecasts. Here
      regulations, information dissemination throughout a fiscal year, and interactions
      among financial analysts are regarded as the proxy for a lower level of
      information disparity. It is found that financial analysts with better access to
      information display contrasting behaviors: a few analysts become bolder and issue
      forecasts independent of other forecasts while the majority of analysts issue
      more accurate forecasts and flock to each other. Main body of our sample of
      optimistic forecasts fits a log-normal distribution, with the tail displaying a
      power law. Based on the Yule process, we propose a model for the dynamics of
      issuing forecasts, incorporating interactions between analysts. Explaining nicely
      empirical data on analyst forecasts, this provides an appealing instance of
      understanding social phenomena in the perspective of complex systems.

PMID- 28498832
TI  - Prenatal exposure to the Great Chinese Famine and mid-age hypertension.
AB  - BACKGROUND: One of the most terrible famines last century was Great Chinese
      Famine (GCF) in 1959~1961 when millions of people died from starving. Under
      nutrition during famine between the Western and Eastern (Dutch Hungry vs. GCF)
      was similar, while cardiovascular consequences might not be the same. Addressing
      such questions may gain new insight into prevention of cardiovascular diseases.
      METHODS: A retrospective cohort of 18,593 participants aged 43-49 years of old,
      was from Suzhou, China. Logistic regression model was used to calculate the
      relative risk (RR) of hypertension and corresponding 95% confidence interval
      (CI). The multivariate RRs were adjusted for age, plasma glucose, triglyceride,
      and cholesterol. RESULTS: The multivariate RRs of systolic and diastolic pressure
      were not significantly elevated in the rural subgroups, but was higher in the
      urban population born in the famine (systolic pressure adjust RR 1.382, 95% CI
      1.235-1.545, diastolic pressure adjust RR 1.569, 95% CI 1.415-1.740). The risks
      of hypertension were significantly higher among the urban subjects than that in
      the rural subgroups (systolic hypertension adjust RR 2.915, 95% CI 2.616-3.249,
      diastolic hypertension adjust RR 4.568, 95% CI 4.079-5.116). Percentile of
      optimal diastolic pressure at mid-age was significantly lower in the urban
      population prenatally exposed to the famine regardless of sexes. However, a
      similar reduction of percentage of optimal systolic pressure was only seen in the
      female, not the male population in the urban region. CONCLUSION: The data suggest
      Asian genetic basis was not able to block famine-programmed vascular diseases as
      that happened in Europe, and the programmed problems due to under-nutrition could
      be reversed after birth. Protective mechanisms may be related to diet habits
      before age of 30 years old, which is important contribution to early prevention
      of hypertension.

PMID- 28498833
TI  - Assessment of the quality of DNA from various formalin-fixed paraffin-embedded
      (FFPE) tissues and the use of this DNA for next-generation sequencing (NGS) with
      no artifactual mutation.
AB  - Formalin-fixed, paraffin-embedded (FFPE) tissues used for pathological diagnosis
      are valuable for studying cancer genomics. In particular, laser-capture
      microdissection of target cells determined by histopathology combined with FFPE
      tissue section immunohistochemistry (IHC) enables precise analysis by next
      generation sequencing (NGS) of the genetic events occurring in cancer. The result
      is a new strategy for a pathological tool for cancer diagnosis: 'microgenomics'.
      To more conveniently and precisely perform microgenomics, we revealed by
      systematic analysis the following three details regarding FFPE DNA compared with
      paired frozen tissue DNA. 1) The best quality of FFPE DNA is obtained by tissue
      fixation with 10% neutral buffered formalin for 1 day and heat treatment of
      tissue lysates at 95 degrees C for 30 minutes. 2) IHC staining of FFPE tissues
      decreases the quantity and quality of FFPE DNA to one-fourth, and antigen
      retrieval (at 120 degrees C for 15 minutes, pH 6.0) is the major reason for this
      decrease. 3) FFPE DNA prepared as described herein is sufficient for NGS. For non
      mutated tissue specimens, no artifactual mutation occurs during FFPE preparation,
      as shown by precise comparison of NGS of FFPE DNA and paired frozen tissue DNA
      followed by validation. These results demonstrate that even FFPE tissues used for
      routine clinical diagnosis can be utilized to obtain reliable NGS data if
      appropriate conditions of fixation and validation are applied.

PMID- 28498834
TI  - Expression of MYSM1 is associated with tumor progression in colorectal cancer.
AB  - Colorectal cancer, the third most common cancer in both men and women, has
      gradually increased in recent years. MYSM1has been investigated as a regulator of
      hematopoiesis and lymphocyte development in human. It has been reported that some
      tumor-related genes were modulated by MYSM1. However, its exact role in cancer
      development remains unclear. Herein, we aimed to examine the expression level of
      MYSM1 in tumor tissues and its correlation with clinicopathology and survivals of
      patients with colorectal cancer (CRC).MYSM1expressions in tumor specimens
      resected from 123 CRC patients were detected by immunochemistry and Western blot
      analysis. The results showed that MYSM1 was significantly highly expressed in
      carcinoma tissues compared with adjacent normal mucosa tissues (P<0.05).
      Correlation analyses by Pearson's chi-square test demonstrated that MYSM1 in
      tumors was positively correlated with tumor status (pathological assessment of
      the primary tumor (pT, P<0.001), regional lymph nodes (pN, P = 0.013), distant
      metastasis (pM, P<0.001)) and clinic stage (P<0.001); Whereas, MYSM1 was not
      associated with tumor size of CRC patients and was positively associated with
      tumor differentiation grade (P = 0.015). Patients with positiveMYSM1expression
      showed poor survival compared with the MYSM1 negative group
      (P<0.001).Simultaneously, multivariate Cox regression analysis indicated
      thatMYSM1 expression in tumor cells was an independent factor for reduced overall
      survival in CRC patients (P<0.001).Additionally,MYSM1 in CRC SW480 cells was
      silenced by small interference RNA (siRNA) technology. Scratch assay and
      Transwell assay showed that MYSM1 silencing decreased migration and invasion
      abilities of SW480 cells. These data suggested that expression of MYSM1 was
      associated with the progression of CRC and might be a potential biomarker for
      clinical prognosis.

PMID- 28498835
TI  - Is traditional male circumcision effective as an HIV prevention strategy?
      Evidence from Lesotho.
AB  - In many developing countries, male circumcision has been promoted as an effective
      HIV prevention strategy, and medical randomized controlled trials have indeed
      shown a causal link. However, there is limited empirical evidence to support this
      conclusion in countries where individuals can voluntary opt for different types
      of circumcision. The present study considers male circumcision in Lesotho, where
      HIV prevalence is among the highest in the world (23%). Here, men can opt for one
      of two types of circumcision: traditional male circumcision in initiation
      schools, or the medical option in health clinics. This paper investigates whether
      the former has medical effects on individual HIV status that are as beneficial as
      those shown for the latter. Controlling for the potential individual behavioral
      response after the operation, it was found that circumcision performed in
      initiation schools wholly offset the medical benefits of the surgical procedure.
      This supports anecdotal evidence that the operation performed by traditional
      circumcisers does not have the same protective effect against HIV transmission as
      the medical operation. No evidence of "disinhibition" behavior among circumcised
      men was found, nor differential risky sexual behavior among men circumcised,
      traditionally or medically. Considering that, in Lesotho, traditional male
      circumcision is undertaken by more than 90% of circumcised men, the findings
      highlight the need for further research into how the operation in initiation
      schools is performed and its medical benefits.

PMID- 28498836
TI  - Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents
      with osteogenesis imperfecta - A retrospective cohort study.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective
      tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2).
      Dentinogenesis imperfecta (DGI) and other dental aberrations are common features
      of OI. We investigated the association between collagen I mutations and DGI,
      taurodontism, and retention of permanent second molars in a retrospective cohort
      of 152 unrelated children and adolescents with OI. The clinical examination
      included radiographic evaluations. Teeth from 81 individuals were available for
      histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by
      nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29%
      of the individuals (44/152) and through isolated histological findings in another
      19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with
      a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both
      dentitions while no individual (0/7) with a mutation N-terminal of this point
      exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2
      mutation, 80% (8/10) of those with a glycine substitution located C terminal of
      p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a
      mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition.
      DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had
      missense mutations where glycine to serine was the most prevalent substitution
      (53%). Taurodontism occurred in 18% and retention of permanent second molars in
      31% of the adolescents. Dental aberrations are strongly associated with
      qualitatively changed collagen I. The varying expressivity of DGI is related to
      the location of the collagen I mutation. Genotype information may be helpful in
      identifying individuals with OI who have an increased risk of dental aberrations.

PMID- 28498837
TI  - Whitefly attraction to rosemary (Rosmarinus officinialis L.) is associated with
      volatile composition and quantity.
AB  - Whitefly (Bemisia tabaci) is an important insect pest, causing severe damage to
      agricultural crops. The pest was recorded in a commercial rosemary (Rosmarinus
      officinalis, Lamiaceae) field, colonizing rosemary variety (var.) '2', but not
      '11'. A series of field and controlled laboratory choice bioassays confirmed the
      observed phenomenon. Mature potted plants of the two varieties were randomly
      organized in a lemon verbena (Lippia citrodora) and lemon grass (Cymbopogon spp.)
      fields. Seven days later var. '2' was significantly more colonized by whiteflies
      than var. '11'. Under lab conditions, whiteflies were significantly more
      attracted to var. '2' plantlets than to var. '11' following choice bioassays.
      Furthermore, cotton plants dipped in an essential oil emulsion of var. '2' had
      significantly greater colonization than cotton plants dipped in the essential oil
      emulsion of var. '11'. Similar results were obtained in 'plant-plant', 'plant-no
      plant' as well as, 'essential oil-essential oil' choice bioassay designs.
      Analyses of the essential oils of the two varieties identified a set of common
      and unique volatiles in each variety. Among these volatiles were beta
      caryophyllene and limonene, two compounds known to be associated with plant
      insect interactions. The attraction of B. tabaci to pure (>95%) beta
      caryophyllene and limonene using a range of concentrations was examined in vitro
      by choice bioassays. The compounds were attractive to the insect at moderate
      concentration, but not at the lowest or highest concentrations used, where the
      insect was not attracted or repelled, respectively. Limonene attracted the
      insects at rates that were 10-fold lower than beta-caryophyllene. The results
      emphasized the role of host plant volatiles in shaping the structure of B. tabaci
      populations in nature and in agricultural systems, and provided insights into the
      factors that contribute to the development of insect populations with unique
      characteristics. The results could also serve for future development of bio
      pesticides and in breeding programs.

PMID- 28498839
TI  - Estimating nutrient uptake requirements for soybean using QUEFTS model in China.
AB  - Estimating balanced nutrient requirements for soybean (Glycine max [L.] Merr) in
      China is essential for identifying optimal fertilizer application regimes to
      increase soybean yield and nutrient use efficiency. We collected datasets from
      field experiments in major soybean planting regions of China between 2001 and
      2015 to assess the relationship between soybean seed yield and nutrient uptake,
      and to estimate nitrogen (N), phosphorus (P), and potassium (K) requirements for
      a target yield of soybean using the quantitative evaluation of the fertility of
      tropical soils (QUEFTS) model. The QUEFTS model predicted a linear-parabolic
      plateau curve for the balanced nutrient uptake with a target yield increased from
      3.0 to 6.0 t ha-1 and the linear part was continuing until the yield reached
      about 60-70% of the potential yield. To produce 1000 kg seed of soybean in China,
      55.4 kg N, 7.9 kg P, and 20.1 kg K (N:P:K = 7:1:2.5) were required in the above
      ground parts, and the corresponding internal efficiencies (IE, kg seed yield per
      kg nutrient uptake) were 18.1, 126.6, and 49.8 kg seed per kg N, P, and K,
      respectively. The QUEFTS model also simulated that a balanced N, P, and K removal
      by seed which were 48.3, 5.9, and 12.2 kg per 1000 kg seed, respectively,
      accounting for 87.1%, 74.1%, and 60.8% of the total above-ground parts,
      respectively. These results were conducive to make fertilizer recommendations
      that improve the seed yield of soybean and avoid excessive or deficient nutrient
      supplies. Field validation indicated that the QUEFTS model could be used to
      estimate nutrient requirements which help develop fertilizer recommendations for
      soybean.

PMID- 28498838
TI  - Assessing medical professionalism: A systematic review of instruments and their
      measurement properties.
AB  - BACKGROUND: Over the last three decades, various instruments were developed and
      employed to assess medical professionalism, but their measurement properties have
      yet to be fully evaluated. This study aimed to systematically evaluate these
      instruments' measurement properties and the methodological quality of their
      related studies within a universally acceptable standardized framework and then
      provide corresponding recommendations. METHODS: A systematic search of the
      electronic databases PubMed, Web of Science, and PsycINFO was conducted to
      collect studies published from 1990-2015. After screening titles, abstracts, and
      full texts for eligibility, the articles included in this study were classified
      according to their respective instrument's usage. A two-phase assessment was
      conducted: 1) methodological quality was assessed by following the COnsensus
      based Standards for the selection of health status Measurement INstruments
      (COSMIN) checklist; and 2) the quality of measurement properties was assessed
      according to Terwee's criteria. Results were integrated using best-evidence
      synthesis to look for recommendable instruments. RESULTS: After screening 2,959
      records, 74 instruments from 80 existing studies were included. The overall
      methodological quality of these studies was unsatisfactory, with reasons
      including but not limited to unknown missing data, inadequate sample sizes, and
      vague hypotheses. Content validity, cross-cultural validity, and criterion
      validity were either unreported or negative ratings in most studies. Based on
      best-evidence synthesis, three instruments were recommended: Hisar's instrument
      for nursing students, Nurse Practitioners' Roles and Competencies Scale, and
      Perceived Faculty Competency Inventory. CONCLUSION: Although instruments
      measuring medical professionalism are diverse, only a limited number of studies
      were methodologically sound. Future studies should give priority to
      systematically improving the performance of existing instruments and to
      longitudinal studies.

PMID- 28498840
TI  - A third generation vaccine for human visceral leishmaniasis and post kala azar
      dermal leishmaniasis: First-in-human trial of ChAd63-KH.
AB  - BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of
      human leishmaniasis, responsible for over 20,000 deaths annually, and post kala
      azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often
      occurs in patients after successful treatment for VL. Lack of effective or
      appropriately targeted cell mediated immunity, including CD8+ T cell responses,
      underlies the progression of VL and progression to PKDL, and can limit the
      therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need
      for prophylactic vaccines against leishmaniasis, the development of therapeutic
      vaccines for use alone or in combined immuno-chemotherapy has been identified as
      an unmet clinical need. Here, we report the first clinical trial of a third
      generation leishmaniasis vaccine, developed intentionally to induce Leishmania
      specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation
      Phase I trial in 20 healthy volunteers to assess the safety, tolerability and
      immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63
      KH is a replication defective simian adenovirus expressing a novel synthetic gene
      (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was
      engineered to reflect repeat domain polymorphisms and arrangements identified
      from clinical isolates. We monitored innate immune responses by whole blood RNA
      Seq and antigen specific CD8+ T cell responses by IFNgamma ELISPOT and
      intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses
      of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that
      ChAd63-KH induced innate immune responses characterized by an interferon
      signature and the presence of activated dendritic cells. Broad and quantitatively
      robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of
      vaccinated subjects. CONCLUSION: The results of this study support the further
      development of ChAd63-KH as a novel third generation vaccine for VL and PKDL.
      TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012
      005596-14) and ISRCTN (07766359).

PMID- 28498841
TI  - Awareness and attitudes towards anthrax and meat consumption practices among
      affected communities in Zambia: A mixed methods approach.
AB  - BACKGROUND: In Zambia, human anthrax cases often occur following cases of animal
      anthrax. Human behaviour has been implicated in this transmission. The objective
      of the study was to explore human behavioural patterns that may contribute to
      outbreaks of anthrax among affected communities. METHODS: A mixed methods study
      was conducted in four districts of Zambia from November 2015 to February 2016. A
      cross sectional survey involving 1,127 respondents, six focus group discussions
      and seven key informant interviews with professional staff were conducted.
      Descriptive statistics on socio-demographic characteristics, awareness of
      anthrax, attitudes towards cattle vaccination and risk factors for anthrax and
      vaccination practices were run using STATA 12 for analysis. RESULTS: Overall, 88%
      of respondents heard about anthrax, 85.1% were aware that anthrax is transmitted
      by eating infected meat and 64.2% knew that animals and humans can be infected
      with anthrax. However, qualitative data suggested that awareness of anthrax
      varied across communities. Qualitative findings also indicated that, in Western
      and Muchinga provinces, human anthrax was transmitted by eating infected beef and
      hippo (Hippopotamus amphibious) meat, respectively. Although survey data
      indicated that 62.2% of respondents vaccinated their animals, qualitative
      interviews and annual vaccination reports indicated low vaccination rates, which
      were attributed to inadequate veterinary service provision and logistical
      challenges. While 82% of respondents indicated that they reported animal deaths
      to veterinary officers, only 13.5% of respondents buried infected carcasses.
      Majority (78.1%) of respondents either ate, sold or shared meat from dead animals
      with other community members. Poverty, lack of access to meat protein and
      economic reasons were cited as drivers for consuming infected meat. CONCLUSIONS:
      Health education campaigns must be intensified to reduce the risk of human
      exposure. Veterinary extension services should be strengthened and cold chain
      facilities decentralized in order to improve accessibility to anthrax vaccine. It
      is also important to involve the affected communities and collaborate with other
      disciplines in order to effectively tackle poverty, improve veterinary services
      and address inherent meat consumption practices within the communities.

PMID- 28498842
TI  - Prognostic significance and predictors of the system inflammation score in
      ovarian clear cell carcinoma.
AB  - Chronic inflammation is a well-known epidemiologic factor of ovarian clear cell
      carcinomas (OCCC), but has an uncertain role in prognosis. We developed a
      systemic inflammation score (SIS) based on preoperative serum albumin and
      neutrophil-to-lymphocyte ratio (NLR) for predicting progression-free survival
      (PFS) and overall survival (OS) in OCCC patients. A retrospective review was
      performed in 155 patients with OCCC undergoing primary debulking and chemotherapy
      at a single institute between 1995 and 2010. Cox regression models were fitted to
      analyze the effect of prognostic factors on PFS and OS. Harrell's concordance
      index was calculated to assess predictive accuracy. The SIS consisting of serum
      albumin and NLR was retained as an independent indicator adjusting for
      traditional clinicopathological features. A high SIS was significantly associated
      with aggressive tumor behavior, platinum resistance, and served as an independent
      predictor of reduced PFS (P = 0.006) and OS (P = 0.019). The SIS had a good
      discrimination ability for the predictive PFS (c-index = 0.712) and OS (c-index =
      0.722). We have developed a system inflammation score for predicting prognosis of
      OCCC patients, which may help stratify patients for postsurgical management.

PMID- 28498843
TI  - When Bitcoin encounters information in an online forum: Using text mining to
      analyse user opinions and predict value fluctuation.
AB  - Bitcoin is an online currency that is used worldwide to make online payments. It
      has consequently become an investment vehicle in itself and is traded in a way
      similar to other open currencies. The ability to predict the price fluctuation of
      Bitcoin would therefore facilitate future investment and payment decisions. In
      order to predict the price fluctuation of Bitcoin, we analyse the comments posted
      in the Bitcoin online forum. Unlike most research on Bitcoin-related online
      forums, which is limited to simple sentiment analysis and does not pay sufficient
      attention to note-worthy user comments, our approach involved extracting keywords
      from Bitcoin-related user comments posted on the online forum with the aim of
      analytically predicting the price and extent of transaction fluctuation of the
      currency. The effectiveness of the proposed method is validated based on Bitcoin
      online forum data ranging over a period of 2.8 years from December 2013 to
      September 2016.

PMID- 28498844
TI  - Windowed persistent homology: A topological signal processing algorithm applied
      to clinical obesity data.
AB  - Overweight and obesity are highly prevalent in the population of the United
      States, affecting roughly 2/3 of Americans. These diseases, along with their
      associated conditions, are a major burden on the healthcare industry in terms of
      both dollars spent and effort expended. Volitional weight loss is attempted by
      many, but weight regain is common. The ability to predict which patients will
      lose weight and successfully maintain the loss versus those prone to regain
      weight would help ease this burden by allowing clinicians the ability to skip
      treatments likely to be ineffective. In this paper we introduce a new windowed
      approach to the persistent homology signal processing algorithm that, when paired
      with a modified, semimetric version of the Hausdorff distance, can differentiate
      the two groups where other commonly used methods fail. The novel approach is
      tested on accelerometer data gathered from an ongoing study at the University of
      Michigan. While most standard approaches to signal processing show no difference
      between the two groups, windowed persistent homology and the modified Hausdorff
      semimetric show a clear separation. This has significant implications for
      clinical decision making and patient care.

PMID- 28498845
TI  - Measurement of tissue azithromycin levels in self-collected vaginal swabs post
      treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS).
AB  - BACKGROUND: Azithromycin is recommended for the treatment of uncomplicated
      urogenital chlamydia infection although the standard 1gram dose sometimes fails
      to eradicate the infection (treatment failure). One hypothesis proposed for
      treatment failure has been insufficient levels of the antibiotic at the site of
      infection. We developed an assay using liquid chromatography and tandem mass
      spectrometry (LC-MS/MS) to measure azithromycin concentration in high-vaginal
      swabs and monitor how concentration changes over time following routine
      azithromycin treatment. METHODS: Azithromycin concentrations were measured in two
      groups of women either within the first 24h of taking a 1g dose (N = 11) or over
      9 days (N = 10). Azithromycin concentrations were normalised to an internal
      standard (leucine enkephalin), and the bulk lipid species phosphatidylcholine
      [PC(34:1)], using an Agilent 6490 triple quadrupole instrument in positive
      ionisation mode. The abundances of azithromycin, PC(34:1), and leu-enkephalin
      were determined by multiple reaction monitoring and absolute levels of
      azithromycin estimated using standard curves prepared on vaginal specimens.
      RESULTS: Vaginal azithromycin concentrations of women were rapidly obtained after
      5h post-treatment (mean concentration = 1031mcg/mg of lipid, range = 173
      2693mcg/mg). In women followed for 9 days, peak concentrations were highest after
      day 2 (mean concentration = 2206mcg/mg, range = 721-5791mcg/mg), and remained
      high for at least 9 days with a mean concentration of 384mcg/mg (range = 139
      1024mcg/mg) on day 9. CONCLUSION: Our study confirmed that a single 1g dose of
      azithromycin is rapidly absorbed and remains in the vagina at relatively high
      levels for at least a week, suggesting that poor antibiotic absorption is
      unlikely to be an explanation for treatment failure.

PMID- 28498846
TI  - MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences
      to tune transcription in the mammalian brain.
AB  - Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several
      neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG)
      is the classical MeCP2 DNA recognition sequence, but additional methylated
      sequence targets have been reported. Here we show by in vitro and in vivo
      analyses that MeCP2 binding to non-CG methylated sites in brain is largely
      confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in
      mouse brain is proportional to mCAC + mCG density and unexpectedly defines large
      genomic domains within which transcription is sensitive to MeCP2 occupancy. Our
      results suggest that MeCP2 integrates patterns of mCAC and mCG in the brain to
      restrain transcription of genes critical for neuronal function.

PMID- 28498848
TI  - Modulation of the growth and metabolic response of cyanobacteria by the
      multifaceted activity of naringenin.
AB  - The interactions between the plant-derived bioflavonoid, naringenin, and
      prokaryotic microalgae representatives (cyanobacteria), were investigated with
      respect to its influence on the growth and metabolic response of these
      microorganisms. To achieve reliable results, the growth of cyanobacteria was
      determined based on measurements of chlorophyll content, morphological changes
      were assessed through microscopic observations, and the chemical response of
      cells was determined using liquid and gas chromatography (HPLC; GC-FID). The
      results show that micromolar levels of naringenin stimulated the growth of
      cyanobacteria. Increased growth was observed for halophilic strains at naringenin
      concentrations below 40 mg L-1, and in freshwater strains at concentrations below
      20 mg L-1. The most remarkable stimulation was observed for the freshwater
      species Nostoc muscorum, which had a growth rate that was up to 60% higher than
      in the control. When naringenin was examined at concentrations above 40 mg L-1,
      the growth of the tested microorganisms was inhibited. Simultaneously, an
      intensive excretion of exopolysaccharides was observed. Microscopic observations
      strongly suggest that these effects resulted from a structural disturbance of
      cyanobacterial cell walls that was exerted by naringenin. This phenomenon, in
      combination with the absorption of naringenin into cell wall structures,
      influenced cell permeability and thus the growth of bacteria. Fortunately, almost
      all the naringenin added to the culture was incorporated into to cell
      substructures and could be recovered through extraction, raising the possibility
      that this modulator could be recycled.

PMID- 28498847
TI  - Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV
      chronically infected macaques.
AB  - Myeloid derived suppressor cells (MDSCs), which suppress anti-tumor or anti-viral
      immune responses, are expanded in the peripheral blood and tissues of
      patients/animals with cancer or viral infectious diseases. We here show that in
      chronic SIV infection of Indian rhesus macaques, the frequency of MDSCs in the
      bone marrow (BM) was paradoxically and unexpectedly decreased, but increased in
      peripheral blood. Reduction of BM MDSCs was found in both CD14+MDSC and Lin
      CD15+MDSC subsets. The reduction of MDSCs correlated with high plasma viral loads
      and low CD4+ T cell counts, suggesting that depletion of BM MDSCs was associated
      with SIV/AIDS disease progression. Of note, in SHIVSF162P4-infected macaques,
      which naturally control viral replication within a few months of infection, the
      frequency of MDSCs in the bone marrow was unchanged. To investigate the
      mechanisms by which BM MDSCs were reduced during chronic SIV infection, we tested
      several hypotheses: depletion due to viral infection, alterations in MDSC
      trafficking, and/or poor MDSC replenishment. We found that the possible
      mobilization of MDSCs from BM to peripheral tissues and the slow self
      replenishment of MDSCs in the BM, along with the viral infection-induced
      depletion, all contribute to the observed BM MDSC reduction. We first demonstrate
      MDSC SIV infection in vivo. Correlation between BM CD14+MDSC reduction and CD8+ T
      cell activation in tissues is consistent with decreased immune suppression by
      MDSCs. Thus, depletion of BM MDSCs may contribute to the pathologic immune
      activation during chronic SIV infection and by extension HIV infection.

PMID- 28498849
TI  - Percutaneous coronary intervention with second-generation drug-eluting stent
      versus bare-metal stent: Systematic review and cost-benefit analysis.
AB  - BACKGROUND: Drug-eluting stents (DESs) were considered as ground-breaking
      technology promising to eradicate restenosis and the necessity to perform
      multiple revascularization procedures subsequent to percutaneous coronary
      intervention. Soon after DESs were released on the market, however, there were
      reports of a potential increase in mortality and of early or late thrombosis. In
      addition, DESs are far more expensive than bare-metal stents (BMSs), which has
      led to their limited use in many countries. The technology has improved over the
      last few years with the second generation of DESs (DES-2). Moreover, costs have
      come down and an improved safety profile with decreased thrombosis has been
      reported. OBJECTIVE: Perform a cost-benefit analysis of DES-2s versus BMSs in the
      context of a publicly funded university hospital in Quebec, Canada. METHODS: A
      systematic review of meta-analyses was conducted between 2012 and 2016 to extract
      data on clinical effectiveness. The clinical outcome of interest for the cost
      benefit analysis was target-vessel revascularization (TVR). Cost units are those
      used in the Quebec health-care system. The cost-benefit analysis was based on a 2
      year perspective. Deterministic and stochastic models (discrete-event simulation)
      were used, and various risk factors of reintervention were considered. RESULTS:
      DES-2s are much more effective than BMSs with respect to TVR rate ratio (i.e.,
      0.29 to 0.62 in more recent meta-analyses). DES-2s seem to cause fewer deaths and
      in-stent thrombosis than BMSs, but results are rarely significant, with the
      exception of the cobalt-chromium everolimus DES. The rate ratio of myocardial
      infraction is systematically in favor of DES-2s and very often significant.
      Despite the higher cost of DES-2s, fewer reinterventions can lead to huge savings
      (i.e., -$479 to -$769 per patient). Moreover, the higher a patient's risk of
      reintervention, the higher the savings associated with the use of DES-2s.
      CONCLUSION: Despite the higher purchase cost of DES-2s compared to BMSs,
      generalizing their use, in particular for patients at high risk of
      reintervention, should enable significant savings.

PMID- 28498850
TI  - Genome-wide transcriptome profiling of radish (Raphanus sativus L.) in response
      to vernalization.
AB  - Vernalization is a key process for premature bolting. Although many studies on
      vernalization have been reported, the molecular mechanism of vernalization is
      still largely unknown in radish. In this study, we sequenced the transcriptomes
      of radish seedlings at three different time points during vernalization. More
      than 36 million clean reads were generated for each sample and the portions
      mapped to the reference genome were all above 67.0%. Our results show that the
      differentially expressed genes (DEGs) between room temperature and the early
      stage of vernalization (4,845) are the most in all treatments pairs. A series of
      vernalization related genes, including two FLOWERING LOCUS C (FLC) genes, were
      screened according to the annotations. A total of 775 genes were also filtered as
      the vernalization related candidates based on their expression profiles. Cold
      stress responsive genes were also analyzed to further confirm the sequencing
      result. Several key genes in vernalization or cold stress response were validated
      by quantitative RT-PCR (RT-qPCR). This study identified a number of genes that
      may be involved in vernalization, which are useful for other functional genomics
      research in radish.

PMID- 28498851
TI  - Myopia and depressive symptoms among older Chinese adults.
AB  - PURPOSE: Few population-based data support the hypothesis that refractive errors
      are associated with depressive symptoms. We aim to assess the impact of myopia on
      the risk of having depressive symptoms in a community-based cohort of elderly
      Chinese. METHODS: A community-based cross-sectional study of 4611 Chinese adults
      aged 60 years or older was conducted. Depressive symptoms were measured using the
      9-item Patient Health Questionnaire (PHQ-9) depression scale in 4597 adults.
      Refraction was determined by auto-refraction followed by subjective refraction.
      Myopia was defined as spherical equivalent (SE) < -0.50 diopters (D) and high
      myopia as SE < -6.00 D. RESULTS: After adjusting for age, gender, education,
      lifestyle-related exposures, presenting visual acuity and age-related cataract,
      myopic adults were more likely to have any depressive symptoms compared with non
      myopic ones (odds ratio = 1.39; 95% confidence interval 1.04, 1.92). There were
      no significant differences in the risk of having any depressive symptoms between
      those with and without high myopia. Myopia or high myopia was not associated with
      having moderate depressive symptoms. The impact of myopia on depressive symptoms
      was stronger in adults with no formal education compared with those with formal
      education. CONCLUSIONS: Myopia was related with the presence of depressive
      symptoms among older adults.

PMID- 28498852
TI  - Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral
      Sclerosis.
AB  - The main objective of this study was to utilize high field (7T) in vivo proton
      magnetic resonance imaging to increase the ability to detect metabolite changes
      in people with ALS, specifically, to quantify levels of glutamine and glutamine
      separately. The second objective of this study was to correlate metabolic markers
      with clinical outcomes of disease progression. 13 ALS participants and 12 age
      matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR
      spectra were acquired from the left precentral gyrus using a very short echo time
      (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated
      to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA +
      NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P =
      0.005, respectively) indicating neuronal injury and/or loss in the precentral
      gyrus. tNA correlated with disease progression as measured by forced vital
      capacity (FVC) (P = 0.014; Rrho = 0.66) and tNA/tCr correlated with overall
      functional decline as measured by worsening of the ALS Functional Rating Scale
      Revised (ALSFRS-R) (P = 0.004; Rrho = -0.74). These findings underscore the
      importance of NAA as a reliable biomarker for neuronal injury and disease
      progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared
      to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the
      two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC
      (P = 0.013; Rrho = 0.66), a clinical marker of disease progression. The decrease
      in Glu is most likely driven by intracellular Glu loss due to neuronal loss and
      degeneration. Neither choline containing components (Cho), a marker for cell
      membrane turnover, nor myo-Inositol (mI), a suspected marker for
      neuroinflammation, showed significant differences between the two groups.
      However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rrho =
      0.74), which may reflect a relative increase of activated microglia around motor
      neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to
      study molecular changes related to neuronal injury and/or loss in people with
      ALS.

PMID- 28498853
TI  - Safety and immunogenicity of an inactivated whole cell tuberculosis vaccine
      booster in adults primed with BCG: A randomized, controlled trial of DAR-901.
AB  - BACKGROUND: Development of a tuberculosis vaccine to boost BCG is a major
      international health priority. SRL172, an inactivated whole cell booster derived
      from a non-tuberculous mycobacterium, is the only new vaccine against
      tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present
      study we sought to determine if a three-dose series of DAR-901 manufactured from
      the SRL172 master cell bank by a new, scalable method was safe and immunogenic.
      METHODS: We performed a single site, randomized, double-blind, controlled, Phase
      1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the
      United States. Healthy adult subjects age 18-65 with prior BCG immunization and a
      negative interferon-gamma release assay (IGRA) were enrolled in cohorts of 16
      subjects and randomized to three injections of DAR-901 (n = 10 per cohort), or
      saline placebo (n = 3 per cohort), or two injections of saline followed by an
      injection of BCG (n = 3 per cohort; 1-8 x 106 CFU). Three successive cohorts were
      enrolled representing DAR-901 at 0.1, 0.3, and 1 mg per dose. Randomization was
      performed centrally and treatments were masked from staff and volunteers.
      Subsequent open label cohorts of HIV-negative/IGRA-positive subjects (n = 5) and
      HIV-positive subjects (n = 6) received three doses of 1 mg DAR-901. All subjects
      received three immunizations at 0, 2 and 4 months administered as 0.1 mL
      injections over the deltoid muscle alternating between right and left arms. The
      primary outcomes were safety and immunogenicity. Subjects were followed for 6
      months after dose 3 for safety and had phlebotomy performed for safety studies
      and immune assays before and after each injection. Immune assays using peripheral
      blood mononuclear cells included cell-mediated IFN-gamma responses to DAR-901
      lysate and to Mycobacterium tuberculosis (MTB) lysate; serum antibody to M.
      tuberculosis lipoarabinomannan was assayed by ELISA. RESULTS: DAR-901 had an
      acceptable safety profile and was well-tolerated at all dose levels in all
      treated subjects. No serious adverse events were reported. Median (range) 7-day
      erythema and induration at the injection site for 1 mg DAR-901 were 10 (4-20) mm
      and 10 (4-16) mm, respectively, and for BCG, 30 (10-107) mm and 38 (15-55) mm,
      respectively. Three mild AEs, all headaches, were considered possibly related to
      DAR-901. No laboratory or vital signs abnormalities were related to immunization.
      Compared to pre-vaccination responses, three 1 mg doses of DAR-901 induced
      statistically significant increases in IFN-gamma response to DAR-901 lysate and
      MTB lysate, and in antibody responses to M. tuberculosis lipoarabinomannan. Ten
      subjects who received 1 mg DAR-901 remained IFN-gamma release assay (IGRA)
      negative after three doses of vaccine. CONCLUSIONS: A three-injection series of
      DAR-901 was well-tolerated, had an acceptable safety profile, and induced
      cellular and humoral immune responses to mycobacterial antigens. DAR-901 is
      advancing to efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02063555.

PMID- 28498855
TI  - Reversible integer wavelet transform for blind image hiding method.
AB  - In this article, a blind data hiding reversible methodology to embed the secret
      data for hiding purpose into cover image is proposed. The key advantage of this
      research work is to resolve the privacy and secrecy issues raised during the data
      transmission over the internet. Firstly, data is decomposed into sub-bands using
      the integer wavelets. For decomposition, the Fresnelet transform is utilized
      which encrypts the secret data by choosing a unique key parameter to construct a
      dummy pattern. The dummy pattern is then embedded into an approximated sub-band
      of the cover image. Our proposed method reveals high-capacity and great
      imperceptibility of the secret embedded data. With the utilization of family of
      integer wavelets, the proposed novel approach becomes more efficient for hiding
      and retrieving process. It retrieved the secret hidden data from the embedded
      data blindly, without the requirement of original cover image.

PMID- 28498856
TI  - Patterns of intravenous fluid resuscitation use in adult intensive care patients
      between 2007 and 2014: An international cross-sectional study.
AB  - BACKGROUND: In 2007, the Saline versus Albumin Fluid Evaluation-Translation of
      Research Into Practice Study (SAFE-TRIPS) reported that 0.9% sodium chloride
      (saline) and hydroxyethyl starch (HES) were the most commonly used resuscitation
      fluids in intensive care unit (ICU) patients. Evidence has emerged since 2007
      that these fluids are associated with adverse patient-centred outcomes. Based on
      the published evidence since 2007, we sought to determine the current type of
      fluid resuscitation used in clinical practice and the predictors of fluid choice
      and determine whether these have changed between 2007 and 2014. METHODS: In 2014,
      an international, cross-sectional study was conducted (Fluid-TRIPS) to document
      current patterns of intravenous resuscitation fluid use and determine factors
      associated with fluid choice. We examined univariate and multivariate
      associations between patients and prescriber characteristics, geographical region
      and fluid type. Additionally, we report secular trends of resuscitation fluid use
      in a cohort of ICUs that participated in both the 2007 and 2014 studies.
      Regression analysis were conducted to determine changes in the administration of
      crystalloid or colloid between 2007 and 2014. FINDINGS: In 2014, a total of 426
      ICUs in 27 countries participated. Over the 24 hour study day, 1456/6707 (21.7%)
      patients received resuscitation fluid during 2716 resuscitation episodes.
      Crystalloids were administered to 1227/1456 (84.3%) patients during 2208/2716
      (81.3%) episodes and colloids to 394/1456 (27.1%) patients during 581/2716
      (21.4%) episodes. In multivariate analyses, practice significantly varied between
      geographical regions. Additionally, patients with a traumatic brain injury were
      less likely to receive colloid when compared to patients with no trauma (adjusted
      OR 0.24; 95% CI 0.1 to 0.62; p = 0.003). Patients in the ICU for one or more days
      where more likely to receive colloid compared to patients in the ICU on their
      admission date (adjusted OR 1.75; 95% CI 1.27 to 2.41; p = <0.001). For secular
      trends in fluid resuscitation, 84 ICUs in 17 countries contributed data. In 2007,
      527/1663 (31.7%) patients received fluid resuscitation during 1167 episodes
      compared to 491/1763 (27.9%) patients during 960 episodes in 2014. The use of
      crystalloids increased from 498/1167 (42.7%) in 2007 to 694/960 (72.3%) in 2014
      (odds ratio (OR) 3.75, 95% confidence interval (CI) 2.95 to 4.77; p = <0.001),
      primarily due to a significant increase in the use of buffered salt solutions.
      The use of colloids decreased from 724/1167 (62.0%) in 2007 to 297/960 (30.9%) in
      2014 (OR 0.29, 95% CI 0.19 to 0.43; p = <0.001), primarily due to a decrease in
      the use of HES, but an overall increase in the use of albumin. CONCLUSIONS:
      Clinical practices of intravenous fluid resuscitation have changed between 2007
      and 2014. Geographical location remains a strong predictor of the type of fluid
      administered for fluid resuscitation. Overall, there is a preferential use of
      crystalloids, specifically buffered salt solutions, over colloids. There is now
      an imperative to conduct a trial determining the safety and efficacy of these
      fluids on patient-centred outcomes. TRIAL REGISTRATION: Clinicaltrials.gov: Fluid
      Translation of research into practice study (Fluid-TRIPS) NCT02002013.

PMID- 28498857
TI  - Cost-effectiveness of pneumococcal vaccination strategies for the elderly in
      Korea.
AB  - BACKGROUND: Although the 13-valent pneumococcal conjugate vaccine (PCV13) showed
      good efficacy against pneumococcal disease in the the CAPiTA trial, the 23-valent
      pneumococcal polysaccharide vaccination (PPSV23) program has been ongoing for
      older adults aged >= 65 years in Korea since May of 2013. This study aimed to
      evaluate the cost-effectiveness of the current vaccination strategy (a single
      dose PPSV23 vaccination) compared to a single-dose PCV13 vaccination and
      sequential PCV13-PPSV23 vaccinations in the elderly population aged >= 65 years.
      METHODS: Using a Markov model, the incremental cost-effectiveness ratios (ICERs)
      of three vaccination strategies were assessed in a societal context. The
      transition probabilities, utility weights to estimate quality adjusted life year
      (QALY), and disease treatment costs were either calculated or cited from
      published data and the Health Insurance Review and Assessment Service.
      Simulations were performed in hypothetical cohorts of Korean adults aged >= 19
      years. The vaccine effectiveness of PPSV23 was cited from a Cochrane Review
      report, while PCV13 effectiveness data were gathered from the CAPiTA trial.
      RESULTS: Current PPSV23 vaccination strategies were cost-effective (ICER, $25,786
      per QALY). However, the administration of PCV13 as a substitute for PPSV23 was
      shown to be more cost-effective than PPSV23 vaccination (ICER, $797 per QALY).
      Sequential PCV13-PPSV23 vaccination was also more cost-effective than PPSV23 for
      elderly people aged >= 65 years. In sensitivity analysis assuming significant
      PPSV23 effectiveness (50%) against non-bacteremic pneumococcal pneumonia, the
      PCV13 vaccination strategy was superior to the PPSV23 vaccination strategy in
      terms of cost-effectiveness. CONCLUSION: The results suggest that PCV13
      vaccination is more cost-effective in elderly subjects aged >= 65 years compared
      to the current PPSV23 vaccination strategy. When complete data is obtained in
      2018 on the maximal herd effects of childhood PCV13 immunization, the incidence
      of pneumococcal pneumonia and the cost-effectiveness of vaccination strategies
      need to be reassessed.

PMID- 28498854
TI  - Single-trait and multi-trait genome-wide association analyses identify novel loci
      for blood pressure in African-ancestry populations.
AB  - Hypertension is a leading cause of global disease, mortality, and disability.
      While individuals of African descent suffer a disproportionate burden of
      hypertension and its complications, they have been underrepresented in genetic
      studies. To identify novel susceptibility loci for blood pressure and
      hypertension in people of African ancestry, we performed both single and multiple
      trait genome-wide association analyses. We analyzed 21 genome-wide association
      studies comprised of 31,968 individuals of African ancestry, and validated our
      results with additional 54,395 individuals from multi-ethnic studies. These
      analyses identified nine loci with eleven independent variants which reached
      genome-wide significance (P < 1.25*10-8) for either systolic and diastolic blood
      pressure, hypertension, or for combined traits. Single-trait analyses identified
      two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one
      novel locus (FRMD3) for blood pressure. At these three loci, as well as at
      GRP20/CDH17, associated variants had alleles common only in African-ancestry
      populations. Functional annotation showed enrichment for genes expressed in
      immune and kidney cells, as well as in heart and vascular cells/tissues.
      Experiments driven by these findings and using angiotensin-II induced
      hypertension in mice showed altered kidney mRNA expression of six genes,
      suggesting their potential role in hypertension. Our study provides new evidence
      for genes related to hypertension susceptibility, and the need to study African
      ancestry populations in order to identify biologic factors contributing to
      hypertension.

PMID- 28498858
TI  - Does stroke volume variation predict fluid responsiveness in children: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: Stroke volume variation (SVV) is a reliable predictor of fluid
      responsiveness in adult patients. However, the predictive value of SVV is
      uncertain in pediatric patients. We performed the first systematic meta-analysis
      to evaluate the diagnostic value of SVV in predicting fluid responsiveness in
      children. METHODS: PUBMED, EMBASE, and Cochrane Central Register of Controlled
      Trials were searched up to December 2016. Original studies assessing the
      diagnostic accuracy of SVV in predicting fluid responsiveness in children were
      considered to be eligible. A random-effects model was used to calculate pooled
      values of sensitivity, specificity and diagnostic odds ratio with 95% CI. The
      summary receiver operating characteristic curve was estimated and area under the
      curve was calculated. Quality of the studies was assessed with the QUADAS-2 tool.
      RESULTS: Six studies with a total of 279 fluid boluses in 224 children were
      included. The analysis demonstrated a pooled sensitivity of 0.68 (95% CI,0.59
      0.76), pooled specificity of 0.65 (95% CI, 0.57-0.73), pooled diagnostic odds
      ratio of 8.24 (95% CI, 2.58-26.30), and the summary area under the summary
      receiver operating characteristic curve of 0.81. However, significant inter-study
      heterogeneity was found (p<0.05, I2 = 61.3%), likely due to small sample size and
      diverse study characteristics. CONCLUSIONS: Current evidence suggests that SVV
      was of diagnostic value in predicting fluid responsiveness in children under
      mechanical ventilation. Given the high heterogeneity of published data, further
      studies are needed to confirm the diagnostic accuracy of SVV in predicting fluid
      responsiveness in pediatric patients.

PMID- 28498859
TI  - USP9X counteracts differential ubiquitination of NPHP5 by MARCH7 and BBS11 to
      regulate ciliogenesis.
AB  - Ciliogenesis is a fundamental biological process central to human health.
      Precisely how this process is coordinated with the cell cycle remains an open
      question. We report that nephrocystin-5 (NPHP5/IQCB1), a positive regulator of
      ciliogenesis, is a stable and low turnover protein subjected to cycles of
      ubiquitination and deubiquitination. NPHP5 directly binds to a deubiquitinating
      enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin.
      NPHP5 undergoes K63 ubiquitination in a cell cycle dependent manner and K48/K63
      ubiquitination upon USP9X depletion or inhibition. In the G0/G1/S phase, a pool
      of cytoplasmic USP9X recruited to the centrosome by NPHP5 protects NPHP5 from
      ubiquitination, thus favouring cilia assembly. In the G2/M phase, USP9X
      dissociation from the centrosome allows BBS11 to K63 ubiquitinate NPHP5 which
      triggers protein delocalization and loss of cilia. BBS11 is a resident
      centrosomal protein, whereas cytoplasmic USP9X sequesters the majority of MARCH7
      away from the centrosome during interphase. Depletion or inhibition of USP9X
      leads to an accumulation of centrosomal MARCH7 which K48 ubiquitinates NPHP5,
      triggering protein degradation and cilia loss. At the same time, BBS11 K63
      ubiquitinates NPHP5. Our data suggest that dynamic ubiquitination and
      deubiquitination of NPHP5 plays a crucial role in the regulation of ciliogenesis.

PMID- 28498860
TI  - Genetic micro-epidemiology of malaria in Papua Indonesia: Extensive P. vivax
      diversity and a distinct subpopulation of asymptomatic P. falciparum infections.
AB  - BACKGROUND: Genetic analyses of Plasmodium have potential to inform on
      transmission dynamics, but few studies have evaluated this on a local spatial
      scale. We used microsatellite genotyping to characterise the micro-epidemiology
      of P. vivax and P. falciparum diversity to inform malaria control strategies in
      Timika, Papua Indonesia. METHODS: Genotyping was undertaken on 713 sympatric P.
      falciparum and P. vivax isolates from a cross-sectional household survey and
      clinical studies conducted in Timika. Standard population genetic measures were
      applied, and the data was compared to published data from Kalimantan, Bangka,
      Sumba and West Timor. RESULTS: Higher diversity (HE = 0.847 vs 0.625; p = 0.017)
      and polyclonality (46.2% vs 16.5%, p<0.001) were observed in P. vivax versus P.
      falciparum. Distinct P. falciparum substructure was observed, with two
      subpopulations, K1 and K2. K1 was comprised solely of asymptomatic infections and
      displayed greater relatedness to isolates from Sumba than to K2, possibly
      reflecting imported infections. CONCLUSIONS: The results demonstrate the greater
      refractoriness of P. vivax versus P. falciparum to control measures, and risk of
      distinct parasite subpopulations persisting in the community undetected by
      passive surveillance. These findings highlight the need for complimentary new
      surveillance strategies to identify transmission patterns that cannot be detected
      with traditional malariometric methods.

PMID- 28498861
TI  - Modulation of caveolins, integrins and plasma membrane repair proteins in
      anthracycline-induced heart failure in rabbits.
AB  - Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose
      dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area
      of relevant investigation. Caveolins bind, organize and regulate receptors and
      signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and
      related membrane repair proteins can function as cardioprotective proteins.
      Expression of these proteins in anthracycline-induced heart failure has not been
      evaluated. We tested the hypothesis that daunorubicin alters cardioprotective
      protein expression in the heart. Rabbits were administered daunorubicin (3 mg/kg,
      IV) weekly, for three weeks or nine weeks. Nine weeks but not three weeks of
      daunorubicin resulted in progressive reduced left ventricular function. Cav-3
      expression in the heart was unchanged at three weeks of daunorubicin and
      increased in nine week treated rabbits when compared to control hearts. Electron
      microscopy showed caveolae in the heart were increased and mitochondrial number
      and size were decreased after nine weeks of daunorubicin. Activated beta-1
      (beta1) integrin and the membrane repair protein MG53 were increased after nine
      weeks of daunorubicin vs. controls with no change at the three week time point.
      The results suggest a potential pathophysiological role for Cav3, integrins and
      membrane repair in daunorubicin-induced heart failure.

PMID- 28498862
TI  - Severity and duration of diabetic foot ulcer (DFU) before seeking care as
      predictors of healing time: A retrospective cohort study.
AB  - OBJECTIVES: To investigate whether A) duration of ulcer before start of treatment
      in specialist health care, and B) severity of ulcer according to University of
      Texas classification system (UT) at start of treatment (baseline), are
      independent predictors of healing time. METHODS: This retrospective cohort study,
      based on electronic medical record data, included 105 patients from two
      outpatient clinics in Western Norway with a new diabetic foot ulcer during 2009
      2011. The associations of duration of ulcer and ulcer severity with healing time
      were assessed using cumulative incidence curves and subdistribution hazard ratio
      estimated using competing risk regression with adjustment for potential
      confounders. RESULTS: Of the 105 participants, 45.7% achieved ulcer healing,
      36.2% underwent amputations, 9.5% died before ulcer healing and 8.5% were lost to
      follow-up. Patients who were referred to specialist health care by a general
      practitioner >= 52 days after ulcer onset had a 58% (SHR 0.42, CI 0.18-0.98)
      decreased healing rate compared to patients who were referred earlier, in the
      adjusted model. High severity (grade 2/3, stage C/D) according to the UT
      classification system was associated with a decreased healing rate compared to
      low severity (grade1, stage A/B or grade 2, stage A) with SHR (95% CI) equal to
      0.14 (0.05-0.43) after adjustment for referral time and other potential
      confounders. CONCLUSION: Early detection and referral by both the patient and
      general practitioner are crucial for optimal foot ulcer healing. Ulcer grade and
      severity are also important predictors for healing time, and early screening to
      assess the severity and initiation of prompt treatment is important.

PMID- 28498864
TI  - Green material selection for sustainability: A hybrid MCDM approach.
AB  - Green material selection is a crucial step for the material industry to
      comprehensively improve material properties and promote sustainable development.
      However, because of the subjectivity and conflicting evaluation criteria in its
      process, green material selection, as a multi-criteria decision making (MCDM)
      problem, has been a widespread concern to the relevant experts. Thus, this study
      proposes a hybrid MCDM approach that combines decision making and evaluation
      laboratory (DEMATEL), analytical network process (ANP), grey relational analysis
      (GRA) and technique for order performance by similarity to ideal solution
      (TOPSIS) to select the optimal green material for sustainability based on the
      product's needs. A nonlinear programming model with constraints was proposed to
      obtain the integrated closeness index. Subsequently, an empirical application of
      rubbish bins was used to illustrate the proposed method. In addition, a
      sensitivity analysis and a comparison with existing methods were employed to
      validate the accuracy and stability of the obtained final results. We found that
      this method provides a more accurate and effective decision support tool for
      alternative evaluation or strategy selection.

PMID- 28498863
TI  - Notch ligands regulate the muscle stem-like state ex vivo but are not sufficient
      for retaining regenerative capacity.
AB  - Myogenic stem cells are a promising avenue for the treatment of muscular
      disorders. Freshly isolated muscle stem cells have a remarkable engraftment
      ability in vivo, but their cell number is limited. Current conventional culture
      conditions do not allow muscle stem cells to expand in vitro with their bona fide
      engraftment efficiency, requiring the improvement of culture procedures for
      achieving successful cell-therapy for muscle disorders. Here we expanded mouse
      muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to
      activate Notch signaling in vitro and to investigate whether these cells could
      retain their engraftment efficiency. Notch signaling promotes the expansion of
      Pax7+MyoD- mouse muscle stem-like cells and inhibits differentiation even after
      passage in vitro. Treatment with Notch ligands induced the Notch target genes and
      generated PAX7+MYOD- stem-like cells from human myoblasts previously cultured on
      conventional culture plates. However, cells treated with Notch ligands exhibit a
      stem cell-like state in culture, yet their regenerative ability was less than
      that of freshly isolated cells in vivo and was comparable to that of the control.
      These unexpected findings suggest that artificial maintenance of Notch signaling
      alone is insufficient for improving regenerative capacity of mouse and human
      donor-muscle cells and suggest that combinatorial events are critical to achieve
      muscle stem cell and myoblast engraftment potential.

PMID- 28498865
TI  - When do traumatic experiences alter risk-taking behavior? A machine learning
      analysis of reports from refugees.
AB  - Exposure to traumatic stressors and subsequent trauma-related mental changes may
      alter a person's risk-taking behavior. It is unclear whether this relationship
      depends on the specific types of traumatic experiences. Moreover, the association
      has never been tested in displaced individuals with substantial levels of
      traumatic experiences. The present study assessed risk-taking behavior in 56
      displaced individuals by means of the balloon analogue risk task (BART). Exposure
      to traumatic events, symptoms of posttraumatic stress disorder and depression
      were assessed by means of semi-structured interviews. Using a novel statistical
      approach (stochastic gradient boosting machines), we analyzed predictors of risk
      taking behavior. Exposure to organized violence was associated with less risk
      taking, as indicated by fewer adjusted pumps in the BART, as was the reported
      experience of physical abuse and neglect, emotional abuse, and peer violence in
      childhood. However, civil traumatic stressors, as well as other events during
      childhood were associated with lower risk taking. This suggests that the
      association between global risk-taking behavior and exposure to traumatic stress
      depends on the particular type of the stressors that have been experienced.

PMID- 28498866
TI  - Cognitive adaptation in asexual and sexual wasps living in contrasted
      environments.
AB  - Differences in learning and memory dynamics between populations are suspected to
      result from differences in ecological constraints such as resource distribution.
      The two reproductive modes (strains) of the parasitoid wasp Venturia canescens
      share the same geographical areas but live in contrasting habitats: arrhenotokous
      wasps live in the wild (generally orchards), whereas thelytokous ones live mostly
      in stored-products buildings (e.g. granaries). This species thus represents a
      relevant biological model for understanding the relationship between the
      ecological constraints faced by a species and its memory and learning ability. We
      showed that after having laid eggs in presence of both a synthetic odour and
      natural olfactory cues of their host, arrhenotokous wasps exhibited a change in
      their behavioural response towards the synthetic odour that was at least as
      pronounced as in thelytokous ones even though they were faster in their decision
      making process. This is consistent with better learning skills in arrhenotokous
      wasps. The corresponding memory trace persisted in both strains for at least 51
      h. We compare and discuss the learning and memory ablities of both strains as a
      function of their costs and benefits in their preferential habitats.

PMID- 28498867
TI  - Multilocus genotyping of Enterocytozoon bieneusi derived from nonhuman primates
      in southwest China.
AB  - Enterocytozoon bieneusi has been increasingly reported in non-human primates
      (NHPs) in recent years, and this has garnered attention. However, reports of E.
      bieneusi infections in NHPs are limited worldwide. To appreciate the genetic
      diversity and assess the zoonotic potential during the transmission of human
      microsporidiosis, we examined a total of 369 fecal samples from NHPs and
      performed PCR amplification of the ITS gene of E. bieneusi. An infection rate of
      12.5% (46/369) was detected in NHPs, with three known genotypes (D, PigEBITS7,
      and SC02) and a novel genotype (SCM01) characterized. Phylogenetic analysis
      indicated that all four genotypes in our study were classified as zoonotic group
      1. Multilocus genotyping of positive E. bieneusi strains revealed that 36, 37,
      30, and 29 specimens were successfully amplified and sequenced to generate 16,
      six, four, and five types of MS1, MS3, MS4, and MS7 loci, respectively. Twenty
      four specimens were successfully amplified and sequenced at all four loci,
      forming 13 multilocus genotypes (MLGs). The occurrence of zoonotic genotypes
      suggests that zoonotic transmission of E. bieneusi between humans and NHPs has
      probably occurred and NHPs could be a source of human microspordiosis.

PMID- 28498868
TI  - A Drosophila model for developmental nicotine exposure.
AB  - Despite the known health risks of tobacco smoking, many people including pregnant
      women continue smoking. The effects of developmental nicotine exposure are known,
      but the underlying mechanisms are not well understood. Drosophila melanogaster is
      a model organism that can be used for uncovering genetic and molecular mechanisms
      for drugs of abuse. Here I show that Drosophila can be a model to elucidate the
      mechanisms for nicotine's effects on a developing organism. Drosophila reared on
      nicotine food display developmental and behavioral effects similar to those in
      mammals including decreased survival and weight, increased developmental time,
      and decreased sensitivity to acute nicotine and ethanol. The Drosophila nicotinic
      acetylcholine receptor subunit alpha 7 (Dalpha7) mediates some of these effects.
      A novel role for Dalpha7 on ethanol sedation in Drosophila is also shown. Future
      research taking advantage of the genetic and molecular tools for Drosophila will
      allow additional discovery of the mechanisms behind the effects of nicotine
      during development.

PMID- 28498869
TI  - The effectiveness of modern cardiac rehabilitation: A systematic review of recent
      observational studies in non-attenders versus attenders.
AB  - BACKGROUND: The beneficial effects of cardiac rehabilitation (CR) have been
      challenged in recent years and there is now a need to investigate whether current
      CR programmes, delivered in the context of modern cardiology, still benefit
      patients. METHODS: A systematic review of non-randomised controlled studies was
      conducted. Electronic searches of Medline, Embase, CINAHL, science citation index
      (web of science), CIRRIE and Open Grey were undertaken. Non-randomised studies
      investigating the effects of CR were included when recruitment occurred from the
      year 2000 onwards in accordance with significant CR guidance changes from the
      late 1990's. Adult patients diagnosed with acute myocardial infarction (AMI) were
      included. Non-English articles were considered. Two reviewers independently
      screened articles according to pre-defined selection criteria as reported in the
      PROSPERO database (CRD42015024021). RESULTS: Out of 2,656 articles, 8 studies
      involving 9,836 AMI patients were included. Studies were conducted in 6
      countries. CR was found to reduce the risk of all-cause and cardiac-related
      mortality and improve Health-Related Quality of Life (HRQOL) significantly in at
      least one domain. The benefits of CR in terms of recurrent MI were inconsistent
      and no significant effects were found regarding re-vascularisation or re
      hospitalisation following AMI. CONCLUSION: Recent observational evidence draws
      different conclusions to the most current reviews of trial data with respect to
      total mortality and re-hospitalisation, questioning the representativeness of
      historic data in the modern cardiological era. Future work should seek to clarify
      which patient and service level factors determine the likelihood of achieving
      improved all-cause and cardiac mortality and reduced hospital re-admissions.

PMID- 28498871
TI  - Towards implementation of cellular automata in Microbial Fuel Cells.
AB  - The Microbial Fuel Cell (MFC) is a bio-electrochemical transducer converting
      waste products into electricity using microbial communities. Cellular Automaton
      (CA) is a uniform array of finite-state machines that update their states in
      discrete time depending on states of their closest neighbors by the same rule.
      Arrays of MFCs could, in principle, act as massive-parallel computing devices
      with local connectivity between elementary processors. We provide a theoretical
      design of such a parallel processor by implementing CA in MFCs. We have chosen
      Conway's Game of Life as the 'benchmark' CA because this is the most popular CA
      which also exhibits an enormously rich spectrum of patterns. Each cell of the
      Game of Life CA is realized using two MFCs. The MFCs are linked electrically and
      hydraulically. The model is verified via simulation of an electrical circuit
      demonstrating equivalent behaviours. The design is a first step towards future
      implementations of fully autonomous biological computing devices with massive
      parallelism. The energy independence of such devices counteracts their somewhat
      slow transitions-compared to silicon circuitry-between the different states
      during computation.

PMID- 28498870
TI  - Brg1 chromatin remodeling ATPase balances germ layer patterning by amplifying the
      transcriptional burst at midblastula transition.
AB  - Zygotic gene expression programs control cell differentiation in vertebrate
      development. In Xenopus, these programs are initiated by local induction of
      regulatory genes through maternal signaling activities in the wake of zygotic
      genome activation (ZGA) at the midblastula transition (MBT). These programs lay
      down the vertebrate body plan through gastrulation and neurulation, and are
      accompanied by massive changes in chromatin structure, which increasingly
      constrain cellular plasticity. Here we report on developmental functions for
      Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin
      remodeling complexes. Carefully controlled, global Brg1 protein depletion in X.
      tropicalis and X. laevis causes embryonic lethality or developmental arrest from
      gastrulation on. Transcriptome analysis at late blastula, before development
      becomes arrested, indicates predominantly a role for Brg1 in transcriptional
      activation of a limited set of genes involved in pattern specification processes
      and nervous system development. Mosaic analysis by targeted microinjection
      defines Brg1 as an essential amplifier of gene expression in dorsal
      (BCNE/Nieuwkoop Center) and ventral (BMP/Vent) signaling centers. Moreover, Brg1
      is required and sufficient for initiating axial patterning in cooperation with
      maternal Wnt signaling. In search for a common denominator of Brg1 impact on
      development, we have quantitatively filtered global mRNA fluctuations at MBT. The
      results indicate that Brg1 is predominantly required for genes with the highest
      burst of transcriptional activity. Since this group contains many key
      developmental regulators, we propose Brg1 to be responsible for raising their
      expression above threshold levels in preparation for embryonic patterning.

PMID- 28498872
TI  - A sequential model for the structure of health care utilization.
AB  - Traditional measurement models of health care utilization are not able to
      represent the complex structure of health care utilization. In this qualitative
      study, we, therefore, developed a new model to represent the health care
      utilization structure. In Norway and Germany, we conducted episodic interviews,
      participant observation and a concurrent context analysis. Data was analyzed by
      thematic coding in the framework of grounded theory. Consultations do very often
      not only have one single reason for encounter. They are usually not independent
      events but form part of consultation sequences. We could find structural
      differences between Norway and Germany regarding the flow of information between
      consultations and which providers are involved in health care in what way. This
      leads to a sequential model, in which health care utilization is seen as
      sequences of consultations. Such health care utilization sequences consist of
      nodes which are connected by edges. Nodes represent patient-provider contacts and
      edges depict the flow of information. Time and the level of health care providers
      are dimensions in the model. These sequences can be described by different
      measures and aggregated on population level. Thus, the sequential model can be
      further used in analyzing health care utilization quantitatively, e.g., by using
      routine data.

PMID- 28498873
TI  - Associations of androgens with depressive symptoms and cognitive status in the
      general population.
AB  - OBJECTIVES: Associations between androgens and depressive symptoms were mostly
      reported from cross-sectional and patient-based studies. STUDY DESIGN/MAIN
      OUTCOME MEASURES: Longitudinal data from 4,110 participants of the Study of
      Health in Pomerania were used to assess sex-specific associations of baseline
      total and free testosterone, androstenedione and sex hormone-binding globulin
      with incident depressive symptoms and cognitive status at 5- and 10-year follow
      up. RESULTS: Despite sex-specific differences in depressive symptoms prevalence
      at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no
      associations between sex hormones and depressive symptoms. In age-adjusted
      longitudinal analyses, total testosterone was associated with incident depressive
      symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58
      0.92). Similarly, age-adjusted analyses showed a positive association between sex
      hormone-binding globulin and cognitive status in men (beta-coefficient per
      standard deviation: 0.44, 95% confidence interval: 0.13-0.74). In women, age
      adjusted associations of androstenedione with baseline depressive symptoms
      (relative risk: 0.88, 95% confidence interval: 0.77-0.99) were found. None of the
      observed associations remained after multivariable adjustment. CONCLUSIONS: The
      present population-based, longitudinal study revealed inverse associations
      between sex hormones and depressive symptoms. However, the null finding after
      multivariable adjustment suggests, that the observed associations were not
      independent of relevant confounders including body mass index, smoking and
      physical inactivity. Furthermore, the low number of incident endpoints in our non
      clinical population-based sample limited the statistical power and reduced the
      chance to detect a statistically significant effect.

PMID- 28498875
TI  - Predictive models of poly(ethylene-terephthalate) film degradation under multi
      factor accelerated weathering exposures.
AB  - Accelerated weathering exposures were performed on poly(ethylene-terephthalate)
      (PET) films. Longitudinal multi-level predictive models as a function of PET
      grades and exposure types were developed for the change in yellowness index (YI)
      and haze (%). Exposures with similar change in YI were modeled using a linear
      fixed-effects modeling approach. Due to the complex nature of haze formation,
      measurement uncertainty, and the differences in the samples' responses, the
      change in haze (%) depended on individual samples' responses and a linear mixed
      effects modeling approach was used. When compared to fixed-effects models, the
      addition of random effects in the haze formation models significantly increased
      the variance explained. For both modeling approaches, diagnostic plots confirmed
      independence and homogeneity with normally distributed residual errors.
      Predictive R2 values for true prediction error and predictive power of the models
      demonstrated that the models were not subject to over-fitting. These models
      enable prediction under pre-defined exposure conditions for a given exposure time
      (or photo-dosage in case of UV light exposure). PET degradation under cyclic
      exposures combining UV light and condensing humidity is caused by photolytic and
      hydrolytic mechanisms causing yellowing and haze formation. Quantitative
      knowledge of these degradation pathways enable cross-correlation of these lab
      based exposures with real-world conditions for service life prediction.

PMID- 28498874
TI  - Soluble bone-derived osteopontin promotes migration and stem-like behavior of
      breast cancer cells.
AB  - Breast cancer is a leading cause of cancer death in women, with the majority of
      these deaths caused by metastasis to distant organs. The most common site of
      breast cancer metastasis is the bone, which has been shown to provide a rich
      microenvironment that supports the migration and growth of breast cancer cells.
      Additionally, growing evidence suggests that breast cancer cells that do
      successfully metastasize have a stem-like phenotype including high activity of
      aldehyde dehydrogenase (ALDH) and/or a CD44+CD24- phenotype. In the current
      study, we tested the hypothesis that these ALDHhiCD44+CD24- breast cancer cells
      interact with factors in the bone secondary organ microenvironment to facilitate
      metastasis. Specifically, we focused on bone-derived osteopontin and its ability
      to promote the migration and stem-like phenotype of breast cancer cells. Our
      results indicate that bone-derived osteopontin promotes the migration,
      tumorsphere-forming ability and colony-forming ability of whole population and
      ALDHhiCD44+CD24- breast cancer cells in bone marrow-conditioned media (an ex vivo
      representation of the bone microenvironment) (p<=0.05). We also demonstrate that
      CD44 and RGD-dependent cell surface integrins facilitate this functional response
      to bone-derived osteopontin (p<=0.05), potentially through activation of WNK-1
      and PRAS40-related pathways. Our findings suggest that soluble bone-derived
      osteopontin enhances the ability of breast cancer cells to migrate to the bone
      and maintain a stem-like phenotype within the bone microenvironment, and this may
      contribute to the establishment and growth of bone metastases.

PMID- 28498876
TI  - Trace element and metal sequestration in vitellaria and sclerites, and reactive
      oxygen intermediates in a freshwater monogenean, Paradiplozoon ichthyoxanthon.
AB  - Exposure to metals and other trace elements negatively affects infection dynamics
      of monogeneans, including diplozoids, but, physiological mechanisms linked to
      exposure have yet to be documented. In this study sequestration of trace elements
      and reactive oxygen intermediate production in the monogenean, Paradiplozoon
      ichthyoxanthon, was demonstrated. During dissection of host fish, Labeobarbus
      aeneus, the gills were excised and assessed for P. ichthyoxanthon, which were
      removed and frozen for fluorescence microscopy or fixed for transmission electron
      microscopy. Trace elements were sequestered in the vitellaria and sclerites in P.
      ichthyoxanthon, and the presence of reactive oxygen intermediates was observed
      predominantly in the tegument of the parasite. Trace elements and metals
      identified and ranked according to weight percentages (wt%) in the vitellaria
      were Cu > C > Au > O > Cr > Fe > Si while for the sclerites C > Cu > O > Au > Fe
      > Cr > Si were identified. For most element detected, readings were higher in the
      vitellaria than the sclerites, except for C and O which were higher in sclerites.
      Specifically for metals, all levels detected in the vitellaria were greater than
      in sclerites. Based on the proportion of trace elements present in the vitellaria
      and sclerites it appears that most trace elements including metals were
      sequestered in the vitellaria. The results of reactive oxygen intermediate
      production in the tegument of the parasite suggests either trace element
      accumulation takes place across the tegument or results from the action of the
      host's immune response on the parasite. The results serve as the first
      demonstration of trace element sequestration and reactive oxygen intermediates in
      a freshwater monogenean parasite.

PMID- 28498877
TI  - High end of life health care costs and hospitalization burden in inflammatory
      bowel disease patients: A population-based study.
AB  - BACKGROUND: End of life (EOL) care is associated with greater costs, particularly
      for acute care services. In patients with inflammatory bowel disease (IBD), EOL
      costs may be accentuated due to reliance on hospital-based services and expensive
      diagnostic tests and treatments. We aimed to compare EOL health care use and
      costs between IBD and non-IBD decedents. METHODS: We conducted a retrospective
      cohort study of all decedents of Ontario, Canada between 2010 and 2013 using
      linked health administrative data. IBD (N = 2,214) and non-IBD (N = 262,540)
      decedents were compared on total direct health care costs in the last year of
      life and hospitalization time during the last 90 days of life. RESULTS: During
      the last 90 days of life, IBD patients spent an average of 16 days in hospital,
      equal to 2.1 greater adjusted hospital days (95% confidence interval [CI] 1.5-2.8
      days) than non-IBD patients. IBD diagnosis was associated with $7,210 CAD (95% CI
      $5,005 - $9,464) higher adjusted per-patient cost in the last year of life, of
      which 76% was due to excess hospitalization costs. EOL cost of IBD care was
      higher than 15 of 16 studied chronic conditions. Health care costs rose sharply
      in the last 90 days of life, primarily due to escalating hospitalization costs.
      CONCLUSIONS: IBD patients spend more time in hospital and incur substantially
      greater health care costs than other decedents as they approach the EOL. These
      excess costs could be curtailed through avoidance of unnecessary hospitalizations
      and expensive treatments in the setting of irreversible deterioration.

PMID- 28498879
TI  - Nonsurgical Medical Penile Girth Augmentation: Experience-Based Recommendations.
AB  - Penile augmentation is increasingly sought by men who are dissatisfied with the
      size and/or appearance of their penis. However, augmentation procedures are still
      considered to be highly controversial with no standardized recommendations
      reported in the medical literature and limited outcome data. Nevertheless, these
      procedures continue to be performed in increasing numbers in private settings.
      Therefore, there is a need for safe, effective, and minimally invasive procedures
      to be developed, evaluated, and reported in the research literature. In this
      article, we focus particularly on girth enhancement procedures rather than
      lengthening procedures as penile girth appears to be particularly important for
      sexual satisfaction. We discuss the advantages and disadvantages of the common
      techniques to date, with a focus on the minimally invasive injectable girth
      augmentation techniques. Based on considerable operative experience, we offer our
      own suggestions for patient screening, technique selection, and perioperative
      care.

PMID- 28498878
TI  - The malleable gut microbiome of juvenile rainbow trout (Oncorhynchus mykiss):
      Diet-dependent shifts of bacterial community structures.
AB  - Plant-derived protein sources are the most relevant substitutes for fishmeal in
      aquafeeds. Nevertheless, the effects of plant based diets on the intestinal
      microbiome especially of juvenile Rainbow trout (Oncorhynchus mykiss) are yet to
      be fully investigated. The present study demonstrates, based on 16S rDNA
      bacterial community profiling, that the intestinal microbiome of juvenile Rainbow
      trout is strongly affected by dietary plant protein inclusion levels. After first
      feeding of juveniles with either 0%, 50% or 97% of total dietary protein content
      derived from plants, statistically significant differences of the bacterial gut
      community for the three diet-types were detected, both at phylum and order level.
      The microbiome of juvenile fish consisted mainly of the phyla Proteobacteria,
      Firmicutes, Bacteroidetes, Fusobacteria and Actinobacteria, and thus fits the
      salmonid core microbiome suggested in previous studies. Dietary plant proteins
      significantly enhanced the relative abundance of the orders Lactobacillales,
      Bacillales and Pseudomonadales. Animal proteins in contrast significantly
      promoted Bacteroidales, Clostridiales, Vibrionales, Fusobacteriales and
      Alteromonadales. The overall alpha diversity significantly decreased with
      increasing plant protein inclusion levels and with age of experimental animals.
      In order to investigate permanent effects of the first feeding diet-type on the
      early development of the microbiome, a diet change was included in the study
      after 54 days, but no such effects could be detected. Instead, the microbiome of
      juvenile trout fry was highly dependent on the actual diet fed at the time of
      sampling.

PMID- 28498880
TI  - A two-arm multicenter phase II trial of one cycle chemoselection split-dose
      docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two
      cycles of split TPF followed by curative surgery combined with postoperative
      radiotherapy in patients with locally advanced oral and oropharyngeal squamous
      cell cancer (TISOC-1).
AB  - Background: Induction chemotherapy (ICT) with docetaxel, cisplatin and
      fluorouracil (TPF) followed by radiotherapy is an effective treatment option for
      locally advanced head and neck cancer. This phase II study investigated the
      effectivity of a split-dose TPF ICT before surgery for locally advanced
      resectable (stage III/IVA) oral and oropharyngeal cancer. Patients and methods:
      Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2
      docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders
      (reduction tumor volume >=30% after first cycle) received three 3-week cycles and
      non-responders only one cycle before surgery and postoperative
      radio(chemo)therapy (RCT). The primary endpoint was progression-free survival
      rate after 24 months. Secondary endpoints were amongst others overall survival,
      histopathological response to ICT, toxicity, quality of life and swallowing
      function. Results: Fifty-four patients (91% stage IVA, 87% male, 72%
      oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis.
      The progression-free survival rate after 24 months was 88.5% for responders and
      60.6% for non-responders (P = 0.005). The overall survival rate after 24 months
      was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of
      histopathological complete remission of the primary tumor was higher in
      responders (P = 0.015). High-risk classification for postoperative RCT was lower
      in responders (P < 0.0001). The most common grade 3+ adverse event was
      neutropenia in 26% of patients during ICT and mucositis in 13% during
      postoperative RCT. During treatment and follow-up quality of life and swallowing
      function was not different between responders and non-responders. Conclusion:
      Patients with oral and oropharyngeal cancer responding to split-dose TPF before
      surgery and postoperative RCT show good oncological results. The tri-modal
      treatment regime was well tolerated. ICT using tumor response as criterion for
      duration of ICT before surgery of oral and oropharyngeal cancer merits additional
      investigation in a phase III study. Clinical trial number: NCT01108042.

PMID- 28498881
TI  - Can p40 (Polyclonal) Replace p63 (Clone 4A4) in the Cytologic Diagnosis of
      Pulmonary Non-Small Cell Carcinoma?
AB  - Objectives: Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in
      cytology specimens can be challenging. Recent literature showed p40 had higher
      specificity than p63 for this purpose. Methods: We identified 190 cytology cases
      with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry,
      including specimens from fine-needle aspirations (FNAs) and effusions. Results:
      ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases,
      respectively, regardless of specimen site. Among lung FNAs of primary pulmonary
      ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20
      pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with
      FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n
      = 14), more cases were positive for p40 than p63. Conclusions: Polyclonal p40
      yields a level of false positivity in ACAs similar to p63, which is highest in
      effusions and is not limited to lung origin.

PMID- 28498882
TI  - Mutational signatures and mutable motifs in cancer genomes.
AB  - Cancer is a genetic disorder, meaning that a plethora of different mutations,
      whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'.
      Point mutations, chromosomal rearrangements and copy number changes, whether they
      have occurred spontaneously in predisposed individuals or have been induced by
      intrinsic or extrinsic (environmental) mutagens, lead to the activation of
      oncogenes and inactivation of tumor suppressor genes, thereby promoting
      malignancy. This scenario has now been recognized and experimentally confirmed in
      a wide range of different contexts. Over the past decade, a surge in available
      sequencing technologies has allowed the sequencing of whole genomes from liquid
      malignancies and solid tumors belonging to different types and stages of cancer,
      giving birth to the new field of cancer genomics. One of the most striking
      discoveries has been that cancer genomes are highly enriched with mutations of
      specific kinds. It has been suggested that these mutations can be classified into
      'families' based on their mutational signatures. A mutational signature may be
      regarded as a type of base substitution (e.g. C:G to T:A) within a particular
      context of neighboring nucleotide sequence (the bases upstream and/or downstream
      of the mutation). These mutational signatures, supplemented by mutable motifs (a
      wider mutational context), promise to help us to understand the nature of the
      mutational processes that operate during tumor evolution because they represent
      the footprints of interactions between DNA, mutagens and the enzymes of the
      repair/replication/modification pathways.

PMID- 28498884
TI  - Global patient outcomes after elective surgery: prospective cohort study in 27
      low-, middle- and high-income countries.

PMID- 28498883
TI  - Prognostic Significance of Spot Urine Na/K for Longitudinal Changes in Blood
      Pressure and Renal Function: The Nagahama Study.
AB  - BACKGROUND: Urinary sodium-to-potassium ratio (Na/K) represents a simple measure
      of sodium load and has been reported to be associated with blood pressure (BP)
      levels in a cross-sectional setting even with spot measurements. The aim of the
      present large-scale cohort study is to determine prognostic significance of spot
      urine Na/K for longitudinal changes in BP levels and renal function. METHODS: The
      present study population consisted of 7,063 individuals from the general
      population. Clinical parameters were measured at baseline and at a follow-up
      interval of 5 years. RESULTS: Mean systolic BP was slightly increased during the
      follow-up period (overall, 124 +/- 17 to 125 +/- 18 mm Hg; nontreated
      participants, 119 +/- 15 to 122 +/- 17 mm Hg). Although, the urinary Na/K
      demonstrated a linear association with BP in a cross-sectional analysis (P <
      0.001), analysis of repeated measured BP values identified baseline Na/K * time
      interaction, i.e., an intraindividual effect, as an inverse determinant (F =
      76.9, P < 0.001) independently of hypertension status and fasting conditions
      possibly due to regression to the mean of temporary high baseline Na/K values at
      baseline. Spot urine Na/K values were found to be positively associated with
      renal function in a cross-sectional analysis (P < 0.001). Although baseline Na/K
      * time interaction showed inverse associated with renal functional decline (F =
      85.8, P < 0.001), this inverse association might not represent physiological
      relationship in likewise fashion with the analysis for BP. CONCLUSIONS: Spot
      urine Na/K may have limited utility as a prognostic marker of longitudinal BP
      change, as well as renal functional decline.

PMID- 28498885
TI  - PROXiMATE: a database of mutant protein-protein complex thermodynamics and
      kinetics.
AB  - Summary: We have developed PROXiMATE, a database of thermodynamic data for more
      than 6000 missense mutations in 174 heterodimeric protein-protein complexes,
      supplemented with interaction network data from STRING database, solvent
      accessibility, sequence, structural and functional information, experimental
      conditions and literature information. Additional features include complex
      structure visualization, search and display options, download options and a
      provision for users to upload their data. Availability and implementation: The
      database is freely available at http://www.iitm.ac.in/bioinfo/PROXiMATE/ . The
      website is implemented in Python, and supports recent versions of major browsers
      such as IE10, Firefox, Chrome and Opera. Contact: gromiha@iitm.ac.in.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28498886
TI  - Risky Drinkers Underestimate their Own Alcohol Consumption.

PMID- 28498887
TI  - Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene
      Polymorphisms: The Cache County Memory Study.
AB  - Neurotrophins, including nerve-growth factor and brain-derived neurotrophic
      factor, have been implicated in Alzheimer's disease (AD). Associations between AD
      and neurotrophin signaling genes have been inconsistent, with few studies
      examining sex differences in risk. We examined four single-nucleotide
      polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415,
      rs2289656, rs2072446) and risk for AD by sex in a population-based sample of
      older adults. Three thousand four hundred and ninety-nine individuals without
      dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female]
      underwent dementia screening and assessment over four triennial waves. Cox
      regression was used to examine time to AD or right censoring for each SNP. Female
      carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard
      ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93,
      95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of
      the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61%
      lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level
      significance (p = .07). The association between certain neurotrophin gene
      polymorphisms and AD differs by sex and may explain inconsistent findings in the
      literature.

PMID- 28498889
TI  - UK anaesthetists' perspectives and experiences of severe perioperative
      anaphylaxis: NAP6 baseline survey.
AB  - Background: There is limited information on UK anaesthetists' perspectives and
      experiences of perioperative anaphylaxis. This baseline survey of the Sixth
      National Audit Project (NAP6) aimed to identify relevant departmental
      preparedness and practices, and individual experiences, perceptions and drug
      avoidance patterns. Methods: All anaesthetists in 356 UK NHS hospitals were
      invited to complete an electronic survey. Results: 11 104 anaesthetists (77%
      crude response rate) from 341 (96%) hospitals responded. Most had immediate
      access to guidelines for anaphylaxis treatment (87%) and established referral
      pathways for investigation (82%), but a minority reported access to designated
      treatment packs (37%) or an anaphylaxis lead (35%). Anaesthetists reported 1734
      cases of suspected perioperative anaphylaxis in 2014-5 of which 81% were referred
      for specialist investigation and 14% reported to the Medicines and Healthcare
      Products Regulatory Agency (MHRA). In their career, 76% of respondents had seen a
      case of perioperative anaphylaxis (1:7.25 years of practice) and 4% reported a
      death (1:311 years of practice), equivalent to 2.3% of events being fatal. Agents
      most frequently perceived to cause anaphylaxis were antibiotics, particularly
      penicillins, and neuromuscular blocking agents, notably rocuronium. Suxamethonium
      and penicillins were avoided by a higher proportion of respondents than events
      attributed to these drugs whereas the converse was true for atracurium and
      teicoplanin. Conclusions: This is the largest ever survey of anaesthetists'
      practices and experiences relating to perioperative anaphylaxis. It identifies
      gaps in preparedness and referral for further investigation and to the UK MHRA.
      It provides important data about drugs implicated in such events and
      anaesthetists' attitudes to anaphylaxis.

PMID- 28498888
TI  - Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and
      activates stress responses.
AB  - Aims: Mitochondria are important organelles, dedicated to energy production.
      Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone,
      interacts with mitochondrial mRNA and is indispensable for mitochondrial function
      through its regulation of mitochondrial translation in cultured cell lines.
      However, the precise role of p32/C1qbp in vivo is poorly understood because of
      embryonic lethality in the systemic p32-deficient mouse. The goal of this study
      was to examine the physiological function of mitochondrial p32/C1qbp in the
      heart. Methods and results: We investigated the role of p32 in regulating cardiac
      function in mice using a Cre-loxP recombinase technology against p32 with
      tamoxifen-inducible knockdown or genetic ablation during postnatal periods.
      Cardiomyocyte-specific deletion of p32 resulted in contractile dysfunction,
      cardiac dilatation and cardiac fibrosis, compared with hearts of control mice. We
      also found decreased COX1 expression, decreased rates of oxygen consumption and
      increased oxidative stress, indicating that these mice had cardiac mitochondrial
      dysfunction provoked by p32-deficiency at early stage. Next, we investigated
      lifespan in cardiac-specific p32-deficient mice. The mice died beginning at 12
      months and their median lifespan was ~14 months. Cardiac mitochondria in the p32
      deficient mice showed disordered alignment, enlargement and abnormalities in
      their internal structure by electron microscopy. We observed that, in p32
      deficient compared with control myocytes, AMPKalpha was constitutively
      phosphorylated and 4EBP-1 and ribosomal S6K were less phosphorylated, suggesting
      impairment of mammalian target of rapamycin signalling. Finally, we found that
      expression levels of mitokines such as FGF21 and of integrated stress response
      genes were significantly increased. Metabolic analysis demonstrated that the urea
      cycle was impaired in the p32-deficient hearts. Conclusion: These findings
      support a key role for mitochondrial p32 protein in cardiac myocytes modulating
      mitochondrial translation and function, and thereby survival.

PMID- 28498890
TI  - Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of
      4,712 Men With Long-Term Follow-up.
AB  - Semen quality has been suggested to be a biological marker of long-term morbidity
      and mortality; however, few studies have been conducted on this subject. We
      identified 5,370 men seen for infertility at Frederiksberg Hospital, Denmark,
      during 1977-2010, and 4,712 of these men were followed in the Danish National
      Patient Registry until first hospitalization, death, or the end of the study. We
      classified patients according to hospitalizations and the presence of
      cardiovascular disease, diabetes, testicular cancer, or prostate cancer. We found
      a clear association between sperm concentration below 15 million/mL and all-cause
      hospitalizations (hazard ratio = 1.5, 95% confidence interval: 1.4, 1.6) and
      cardiovascular disease (hazard ratio = 1.4, 95% confidence interval: 1.2, 1.6),
      compared with men with a concentration above 40 million/mL. The probabilities for
      hospitalizations were also higher with a low total sperm count and low motility.
      Men with a sperm concentration of 195-200 million/mL were, on average,
      hospitalized for the first time 7 years later than were men with a sperm
      concentration of 0-5 million/mL. Semen quality was associated with long-term
      morbidity, and a significantly higher risk of hospitalization was found, in
      particular for cardiovascular diseases and diabetes mellitus. Our study supports
      the suggestion that semen quality is a strong biomarker of general health.

PMID- 28498891
TI  - Adipose tissue depots and inflammation: effects on plasticity and resident
      mesenchymal stem cell function.
AB  - Adipose tissue (AT) is a highly heterogeneous organ. Beside the heterogeneity
      associated to different tissue types (white, brown, and 'brite') and its location
      related heterogeneity (subcutaneous, visceral, epicardial, and perivascular,
      etc.), AT composition, structure, and functionality are highly dependent on
      individual-associated factors. As such, the pro-inflammatory state associated to
      the presence of obesity and other cardiovascular risk factors (CVRFs) directly
      affects AT metabolism. Furthermore, the adipose-derived stem cells (ASCs) that
      reside in the stromal vascular fraction of AT, besides being responsible for most
      of the plasticity attributed to AT, is an additional source of heterogeneity.
      Thus, ASCs directly contribute to AT homeostasis, cell renewal, and spontaneous
      repair. These ASCs share many properties with the bone-marrow mesenchymal stem
      cells (i.e. potential to differentiate towards multiple tissue lineages, and
      angiogenic, antiapoptotic, and immunomodulatory properties). Moreover, ASCs show
      clear advantages in terms of accessibility and quantity of available sample,
      their easy in vitro expansion, and the possibility of having an autologous
      source. All these properties point out towards a potential use of ASCs in
      regenerative medicine. However, the presence of obesity and other CVRFs induces a
      pro-inflammatory state that directly impacts ASCs proliferation and
      differentiation capacities affecting their regenerative abilities. The focus of
      this review is to summarize how inflammation affects the different AT depots and
      the mechanisms by which these changes further enhance the obesity-associated
      metabolic disturbances. Furthermore, we highlight the impact of obesity-induced
      inflammation on ASCs properties and how those effects impair their plasticity.

PMID- 28498892
TI  - Incident AIDS or Death After Initiation of Human Immunodeficiency Virus Treatment
      Regimens Including Raltegravir or Efavirenz Among Adults in the United States.
AB  - Background.: The long-term effectiveness of human immunodeficiency virus (HIV)
      treatments containing integrase inhibitors is unknown. Methods.: We use
      observational data from the Centers for AIDS Research Network of Integrated
      Clinical Systems and the Centers for Disease Control and Prevention to estimate 4
      year risk of AIDS and all-cause mortality among 415 patients starting a
      raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens
      include emtricitabine and tenofovir disoproxil fumarate). We account for
      confounding and selection bias as well as generalizability by standardization for
      measured variables, and present both observational intent-to-treat and per
      protocol estimates. Results.: At treatment initiation, 12% of patients were
      female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/uL,
      and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an
      AIDS-defining illness or died, and 741 patients left follow-up. After accounting
      for measured differences, the 4-year risk was similar among those starting both
      regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval
      {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among
      those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk
      difference, -0.5 [95% CI, -3.8 to 2.9]). Conclusions.: Raltegravir and efavirenz
      based initial antiretroviral therapy have similar 4-year clinical effects.
      Vigilance regarding longer-term comparative effectiveness of HIV regimens using
      observational data is needed because large-scale experimental data are not
      forthcoming.

PMID- 28498893
TI  - Role of DHX33 in c-Myc-induced cancers.
AB  - Oncogene c-Myc is frequently amplified and activated in human cancers.
      Deregulation of c-Myc protein has been shown to occur in 30% of all human
      cancers, especially in hematopoietic malignancies. As a transcription factor, c
      Myc has been shown to regulate up to 15% of all human genome genes, controlling
      diverse cellular activities including cell cycle, ribosome biogenesis, protein
      synthesis, metabolism, apoptosis and angiogenesis. In this report, we provide
      evidence that the RNA helicase DHX33 is a critical downstream target of c-Myc.
      Myc binds to DHX33 upstream promoter region and stimulates its transcription.
      Elevated DHX33 protein is pivotal for c-Myc to drive tumor formation. Knockdown
      of DHX33 to basal levels in c-Myc overexpressing cells significantly reduced cell
      proliferation, cell migration and anchorage-independent cell growth in vitro and
      in vivo. Additionally, we found that DHX33 promotes MMP9, MMP14 and urokinase
      type plasminogen activator (PLAU) transcription by directly binding to their
      promoters, thus promoting cancer cell migration. DHX33 protein was overexpressed
      in a certain subset of human non-Hodgkin's lymphoma tissues. Finally, knockdown
      of DHX33 significantly inhibits the development of Myc-induced acute myeloid
      leukemia. Overall, our results implicate the important role for DHX33 in Myc
      induced cancer and point toward its potential therapeutic value in Myc driven
      cancers.

PMID- 28498895
TI  - Acute Illness Among Surfers After Exposure to Seawater in Dry- and Wet-Weather
      Conditions.
AB  - Rainstorms increase levels of fecal indicator bacteria in urban coastal waters,
      but it is unknown whether exposure to seawater after rainstorms increases rates
      of acute illness. Our objective was to provide the first estimates of rates of
      acute illness after seawater exposure during both dry- and wet-weather periods
      and to determine the relationship between levels of indicator bacteria and
      illness among surfers, a population with a high potential for exposure after
      rain. We enrolled 654 surfers in San Diego, California, and followed them
      longitudinally during the 2013-2014 and 2014-2015 winters (33,377 days of
      observation, 10,081 surf sessions). We measured daily surf activities and illness
      symptoms (gastrointestinal illness, sinus infections, ear infections, infected
      wounds). Compared with no exposure, exposure to seawater during dry weather
      increased incidence rates of all outcomes (e.g., for earache or infection,
      adjusted incidence rate ratio (IRR) = 1.86, 95% confidence interval (CI): 1.27,
      2.71; for infected wounds, IRR = 3.04, 95% CI: 1.54, 5.98); exposure during wet
      weather further increased rates (e.g., for earache or infection, IRR = 3.28, 95%
      CI: 1.95, 5.51; for infected wounds, IRR = 4.96, 95% CI: 2.18, 11.29). Fecal
      indicator bacteria measured in seawater (Enterococcus species, fecal coliforms,
      total coliforms) were strongly associated with incident illness only during wet
      weather. Urban coastal seawater exposure increases the incidence rates of many
      acute illnesses among surfers, with higher incidence rates after rainstorms.

PMID- 28498896
TI  - Inhibition of PRDM14 expression in pancreatic cancer suppresses cancer stem-like
      properties and liver metastasis in mice.
AB  - Pancreatic cancer is one of the most lethal types of cancer, with aggressive
      properties characterized by metastasis, recurrence and drug resistance. Cancer
      stem cells are considered to be responsible for these properties. PRDM14, a
      transcriptional regulator that maintains pluripotency in embryonic stem cells, is
      overexpressed in some cancers. Here, we assessed PRDM14 expression and the
      effects of PRDM14 knockdown on cancer stem-like phenotypes in pancreatic cancer.
      We observed that PRDM14 protein was overexpressed in pancreatic cancer tissues
      compared with normal pancreatic tissues. Using lentiviral shRNA-transduced
      pancreatic cancer cells, we found that PRDM14 knockdown decreased sphere
      formation, number of side population and cell surface marker-positive cells and
      subcutaneous xenograft tumors and liver metastasis in mice. This was accompanied
      by upregulation of some microRNAs (miRNAs), including miR-125a-3p. miR-125a-3p, a
      tumor suppressor that is down-regulated in pancreatic cancer, has been suggested
      to regulate the expression of the Src-family kinase, Fyn. In PRDM14-knockdown
      cells, Fyn was expressed at lower levels and downstream proteins were less
      activated. These changes were considered to cause suppression of the above cancer
      phenotypes. In addition, we used small interfering RNA (siRNA)-based therapy
      targeting PRDM14 in a mouse model of liver metastasis induced using MIA-PaCa2
      cells, and this treatment significantly decreased metastasis and in vitro
      migration. Taken together, these results suggest that targeting the
      overexpression of PRDM14 suppresses cancer stem-like phenotypes, including liver
      metastasis, via miRNA regulation and siRNA-based therapy targeting it shows
      promise as a treatment for patients with pancreatic cancer.

PMID- 28498894
TI  - The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint
      NHLBI/NIA Workshop.
AB  - Death from chronic lung disease is increasing and chronic obstructive pulmonary
      disease has become the third leading cause of death in the United States in the
      past decade. Both chronic and acute lung diseases disproportionately affect
      elderly individuals, making it likely that these diseases will become more
      frequent and severe as the worldwide population ages. Chronic lung diseases are
      associated with substantial morbidity, frequently resulting in exercise limiting
      dyspnea, immobilization, and isolation. Therefore, effective strategies to
      prevent or treat lung disease are likely to increase healthspan as well as life
      span. This review summarizes the findings of a joint workshop sponsored by the
      NIA and NHLBI that brought together investigators focused on aging and lung
      biology. These investigators encouraged the use of genetic systems and aged
      animals in the study of lung disease and the development of integrative systems
      based platforms that can dynamically incorporate data sets that describe the
      genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging
      lung in health and disease. Further research was recommended to integrate
      benchmark biological hallmarks of aging in the lung with the pathobiology of
      acute and chronic lung diseases with divergent pathologies for which advanced age
      is the most important risk factor.

PMID- 28498897
TI  - Which technique of cusp repair is durable in reimplantation procedure?
AB  - OBJECTIVES: We aimed to ascertain the durability of cusp repair techniques used
      in reimplantation procedures. METHODS: Between 2000 and 2015, 249 patients (mean
      age, 49 +/- 17 years) with aortic insufficiency underwent the reimplantation
      procedure. The pathology was acute aortic dissection in 24 and non-dissection in
      225 patients. Preoperative aortic regurgitation (AR) was absent in 9, 1+ in 19,
      2+ in 20, 3+ in 71 and 4+ in 120 patients. The mean aortic root and ascending
      aortic diameters were 47 +/- 9 mm and 38 +/- 7 mm, respectively. The following
      techniques of cusp repair were used: none (83), central plication (130), free
      margin reinforcement (57) and patch repair (19). Annual echocardiography was
      performed. Freedom from moderate aortic insufficiency and aortic valve
      reoperation were calculated by the Kaplan-Meier method. Factors influencing the
      freedom from moderate or severe AR were calculated by proportional hazard
      analysis. RESULTS: Mean follow-up period was 56  +/-  44 months. Freedom from
      moderate or severe AR was 82%+/-3% and 77% +/- 4% at 5 and 8 years, respectively,
      whereas freedom from aortic valve reoperation was 93%+/-8% and 87% +/- 3% at 5
      and 8 years, respectively. Recurrent AR and infection were causes of reoperation
      in 13 and 3 patients, respectively. Preoperative cusp prolapse, technique of free
      margin reinforcement used and patch repair were significant factors for recurrent
      AR by proportional hazard analysis. Central plication was not a significant
      factor for recurrent AR. CONCLUSIONS: Preoperative cusp prolapse was a risk
      factor, whereas central plication was not a risk factor for recurrent AR. Free
      margin reinforcement had a positive effect, whereas patch repair had a negative
      effect on aortic valve durability.

PMID- 28498898
TI  - Spatial Asymmetry and Short-Term Suppression Underlie Direction Selectivity of
      Synaptic Excitation in the Mouse Visual Cortex.
AB  - Direction selectivity (DS) of neuronal responses is fundamental for motion
      detection. With in vivo whole-cell voltage-clamp recordings from layer (L)4
      neurons in the mouse visual cortex, we observed a strong correlation between DS
      and spatial asymmetry in the distribution of excitatory input strengths. This
      raises an interesting possibility that the latter may contribute to DS. The
      preferred direction of excitatory input was found from the stronger to weaker
      side of its spatial receptive field. A simple linear summation of asymmetrically
      distributed excitatory responses to stationary flash stimuli however failed to
      predict the correct directionality: it at best resulted in weak DS with preferred
      direction opposite to what was observed experimentally. Further studies with
      sequential 2 flash-bar stimulation revealed a short-term suppression of
      excitatory input evoked by the late bar. More importantly, the level of the
      suppression positively correlated with the relative amplitude of the early-bar
      response. Implementing this amplitude-dependent suppressive interaction can
      successfully predict DS of excitatory input. Our results suggest that via
      nonlinear temporal interactions, the spatial asymmetry can be transformed into
      differential temporal integration of inputs under opposite directional movements.
      This mechanism may contribute to the DS of excitatory inputs to L4 neurons.

PMID- 28498900
TI  - Mid- to long-term results following aortic valve replacement using the Mitroflow
      xeno-pericardial bioprosthesis: somewhat different views from 2 high-volume
      institutions.

PMID- 28498899
TI  - MAGenTA: a Galaxy implemented tool for complete Tn-Seq analysis and data
      visualization.
AB  - Motivation: Transposon insertion sequencing (Tn-Seq) is a microbial systems-level
      tool, that can determine on a genome-wide scale and in high-throughput, whether a
      gene, or a specific genomic region, is important for fitness under a specific
      experimental condition. Results: Here, we present MAGenTA, a suite of analysis
      tools which accurately calculate the growth rate for each disrupted gene in the
      genome to enable the discovery of: (i) new leads for gene function, (ii) non
      coding RNAs; (iii) genes, pathways and ncRNAs that are involved in tolerating
      drugs or induce disease; (iv) higher order genome organization; and (v) host
      factors that affect bacterial host susceptibility. MAGenTA is a complete Tn-Seq
      analysis pipeline making sensitive genome-wide fitness (i.e. growth rate)
      analysis available for most transposons and Tn-Seq associated approaches (e.g.
      TraDis, HiTS, IN-Seq) and includes fitness (growth rate) calculations, sliding
      window analysis, bottleneck calculations and corrections, statistics to compare
      experiments and strains and genome-wide fitness visualization. Availability and
      implementation: MAGenTA is available at the Galaxy public ToolShed repository and
      all source code can be found and are freely available at
      https://vanopijnenlab.github.io/MAGenTA/ . Contact: vanopijn@bc.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28498902
TI  - Reply: Beneficial effect of interleukin-2-based immunomodulation in Alzheimer
      like pathology.

PMID- 28498901
TI  - ECCO-ESCP Consensus on Surgery for Crohn's Disease.

PMID- 28498903
TI  - Efficacy and safety of inhaled anaesthetic for postoperative sedation during
      mechanical ventilation in adult cardiac surgery patients: a systematic review and
      meta-analysis.
AB  - The aim was to evaluate the efficacy and safety of volatile anaesthetic for
      postoperative sedation in adult cardiac surgery patients through a systematic
      review and meta-analysis. We retrieved randomized controlled trials from MEDLINE,
      EMBASE, CENTRAL, Web of Science, clinical trials registries, conference
      proceedings, and reference lists of included articles. Independent reviewers
      extracted data, including patient characteristics, type of intraoperative
      anaesthesia, inhaled anaesthetic used, comparator sedation, and outcomes of
      interest, using pre-piloted forms. We assessed risk of bias using the Cochrane
      Tool and evaluated the strength of the evidence using the GRADE approach. Eight
      studies enrolling 610 patients were included. Seven had a high and one a low risk
      of bias. The times to extubation after intensive care unit (ICU) admission and
      sedation discontinuation were, respectively, 76 [95% confidence interval (CI) 
      150 to - 2, I2=79%] and 74 min (95% CI - 126 to - 23, I2=96%) less in patients
      who were sedated using volatile anaesthetic. There was no difference in ICU or
      hospital length of stay. Patients who received volatile anaesthetic sedation had
      troponin concentrations that were 0.71 ng ml-1 (95% CI 0.23-1.2) lower than
      control patients. Reporting on other outcomes was varied and not suitable for
      meta-analysis. Volatile anaesthetic sedation may be associated with a shorter
      time to extubation after cardiac surgery but no change in ICU or hospital length
      of stay. It is associated with a significantly lower postoperative troponin
      concentration, but the impact of this on adverse cardiovascular outcomes is
      uncertain. Blinded randomized trials using intention-to-treat analysis are
      required. PROSPERO registry number: 2016:CRD42016033874. Available from
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016033874.

PMID- 28498904
TI  - The ACEF II Risk Score for cardiac surgery: updated but still parsimonious.
AB  - Aims: The age, creatinine, and ejection fraction (ACEF) score was introduced in
      2009 and is presently included in the guidelines for myocardial revascularization
      of the European Society of Cardiology and Association for Cardio-Thoracic Surgery
      as a risk stratification tool for surgical and percutaneous myocardial
      revascularization. The present study introduces an updated version of the ACEF
      (ACEF II) inclusive of emergency surgery and pre-operative anaemia. Methods and
      results: The development series includes 7011 consecutive cardiac surgery
      patients operated at a single institution. The validation series includes 1687
      consecutive cardiac surgery patients operated in a different institution. The
      five factors included in the ACEF II were assessed in a multivariable logistic
      regression model testing their independent role as predictors of operative (in
      hospital or 30 days after surgery) mortality. Based on the odds ratio of each
      predictor, the ACEF II score is calculated as age(years)/ejection fraction (%).
      Additional points are attributed to a serum creatinine level > 2 mg/dL (2
      points), emergency surgery (3 points) and anaemia [haematocrit (HCT) < 36%, 0.2
      points per each HCT point below 36%]. The final model was well calibrated.
      Discrimination of the ACEF II (c-statistics 0.814) was significantly (P = 0.041)
      better than the ACEF (c-statistics 0.773) and equal to the EuroSCORE II. In the
      external validation, the ACEF II confirmed a better discrimination than the ACEF
      and good calibration properties. Conclusion: The ACEF II allows the inclusion of
      emergency patients and, through a re-modulation of the coefficients and the
      inclusion of anaemia, appears more adequate to the present cardiac surgery
      scenario.

PMID- 28498905
TI  - Basiliximab for posterior reversible encephalopathy syndrome after lung
      transplantation.
AB  - Posterior reversible encephalopathy syndrome is a neurological complication
      associated with calcineurin inhibitors. There is no consensus regarding the
      continuation of calcineurin inhibitors in the event of posterior reversible
      encephalopathy syndrome. We report 3 cases of posterior reversible encephalopathy
      syndrome among 155 lung transplant recipients (1.9%). The calcineurin inhibitor
      trough level exceeded the therapeutic range in only 1 case. Our findings
      demonstrate that temporary cessation of calcineurin inhibitors and administration
      of basiliximab may be effective strategies for managing posterior reversible
      encephalopathy syndrome.

PMID- 28498906
TI  - Heap: a highly sensitive and accurate SNP detection tool for low-coverage high
      throughput sequencing data.
AB  - Recent availability of large-scale genomic resources enables us to conduct so
      called genome-wide association studies (GWAS) and genomic prediction (GP)
      studies, particularly with next-generation sequencing (NGS) data. The
      effectiveness of GWAS and GP depends on not only their mathematical models, but
      the quality and quantity of variants employed in the analysis. In NGS single
      nucleotide polymorphism (SNP) calling, conventional tools ideally require more
      reads for higher SNP sensitivity and accuracy. In this study, we aimed to develop
      a tool, Heap, that enables robustly sensitive and accurate calling of SNPs,
      particularly with a low coverage NGS data, which must be aligned to the reference
      genome sequences in advance. To reduce false positive SNPs, Heap determines
      genotypes and calls SNPs at each site except for sites at the both ends of reads
      or containing a minor allele supported by only one read. Performance comparison
      with existing tools showed that Heap achieved the highest F-scores with low
      coverage (7X) restriction-site associated DNA sequencing reads of sorghum and
      rice individuals. This will facilitate cost-effective GWAS and GP studies in this
      NGS era. Code and documentation of Heap are freely available from
      https://github.com/meiji-bioinf/heap (29 March 2017, date last accessed) and our
      web site (http://bioinf.mind.meiji.ac.jp/lab/en/tools.html (29 March 2017, date
      last accessed)).

PMID- 28498907
TI  - Complicated infective aortic endocarditis: comparison of different surgical
      strategies.
AB  - OBJECTIVES: The choice of substitute during aortic valve replacement for
      infective endocarditis (IE) is still widely debated. We retrospectively reviewed
      all patients operated for aortic IE and compared groups according to the
      complexity of IE and substitutes implanted. METHODS: From 2000 to 2015, 187
      patients were treated using stentless bioprostheses (SBP) as root replacement (n
      = 30), mechanical prostheses (MP, n = 45) or stented bioprostheses (SP, n = 112)
      (mean follow-up 4.6 years, survival data 100% complete). RESULTS: MP patients
      were younger (42.5 +/- 10.7 vs 57.2 +/- 16.9 years [SBP], 59.1 +/- 14.1 years
      [SP], P < 0.01), but rates of intravenous drug use and chronic dialysis were not
      different. SBP patients more often had root involvement (83.3% vs 33.3% [MP],
      25.9% [SP], P < 0.01) and prosthetic valve endocarditis (53.3% vs 6.7% [MP],
      12.5% [SP], P < 0.01). In-hospital complications and length of stay were not
      different. Thirty-day mortality was 13.3% [SBP], 6.7% [MP] and 12.5% [SP] (P =
      0.53). Five-year survival tended to be superior in SBP (83.3% vs 77.6% [MP],
      67.1% [SP], P = 0.09). In patients with complicated IE (root involvement or
      prosthetic valve endocarditis, n = 77), SBP had superior long-term survival
      (86.9% vs 81.3% [MP], 57.2% [SP], PSBP/MP  = 0.07, PSBP/SP = 0.05). No early
      reinfection (<90 days) occurred in SBP vs 4.4% [MP] and 7.1% [SP] (P = 0.29).
      Reoperation for late reinfection occurred in 6.7% [SBP] vs 11.1% [MP] and 12.5%
      [SP] (P = 0.65). Prosthesis failure occurred in 3.3% [SBP] and 1.8% [SP] (P =
      0.52). CONCLUSIONS: Use of SBP provides favourable outcomes in patients with IE
      with low rates of reinfection and valve deterioration. It seems to be an optimal
      device in patients with complex IE.

PMID- 28498908
TI  - Development, Validation and Application of a Stability Indicating HPLC Method to
      Quantify Lidocaine from Polyethylene-co-Vinyl Acetate (EVA) Matrices and
      Biological Fluids.
AB  - An efficient and cost-effective quantification procedure for lidocaine by HPLC
      has been developed to estimate lidocaine from an EVA matrix, plasma, peritoneal
      fluid and intra-articular fluid (IAF). This method guarantees the resolution of
      lidocaine from the degradation products obtained from alkaline and oxidative
      stress. Chromatographic separation of lidocaine was achieved with a retention
      time of 7 min using a C18 column with a mobile phase comprising acetonitrile and
      potassium dihydrogen phosphate buffer (pH 5.5; 0.02 M) in the ratio of 26:74 at a
      flow rate of 1 mL min-1 with detection at 230 nm. Instability of lidocaine was
      observed to an oxidizing (0.02% H2O2) and alkaline environments (0.1 M NaOH). The
      calibration curve was found to be linear within the concentration range of 0.40
      50.0 MUg/mL. Intra-day and inter-day accuracy ranged between 95.9% and 99.1%,
      with precision (% RSD) below 6.70%. The limit of quantification and limit of
      detection were 0.40 MUg/mL and 0.025 MUg/mL, respectively. The simple extraction
      method described enabled the quantification of lidocaine from an EVA matrix using
      dichloromethane as a solvent. The assay and content uniformity of lidocaine
      within an EVA matrix were 103 +/- 3.60% and 100 +/- 2.60%, respectively. The
      ability of this method to quantify lidocaine release from EVA films was also
      demonstrated. Extraction of lidocaine from plasma, peritoneal fluid and IAF
      followed by HPLC analysis confirmed the utility of this method for ex vivo and in
      vivo studies where the calibration plot was found to be linear from 1.60 to 50.0
      MUg/mL.

PMID- 28498909
TI  - Beneficial effect of interleukin-2-based immunomodulation in Alzheimer-like
      pathology.

PMID- 28498910
TI  - Extra-anatomical bypass in complex and recurrent aortic coarctation and
      hypoplastic arch.
AB  - OBJECTIVES: Our goal was to report the selection schemes, technical variations
      and long-term outcome of extra-anatomical bypass to correct complex, recurrent
      aortic coarctation and hypoplastic aortic arch. METHODS: Between 1989 and 2012,
      53 patients (mean age 13.2 +/- 4.3, median 11.6, range 9-23 years) with complex
      aortic coarctation (n = 33; long-segment hypoplastic aortic arch in 15),
      recurrent coarctation (n = 20; anastomosic pseudoaneurysm in 10), underwent
      correction using extra-anatomical bypass, either with (n = 18: femoral bypass =
      13, left heart bypass = 5) or without (n = 35) extracorporeal circulation via a
      left lateral thoracotomy (n= 48) and combined median sternotomy and median
      laparotomy (n = 5). The decision to use extracorporeal circulation was based on
      the anatomical location of the coarctation, the length of the hypoplasia and a
      history of previous repair. Preoperatively, mean systolic blood pressure was 130
      +/- 30 mmHg at rest and 180 +/- 40 mmHg during exercise, with a mean pressure
      gradient of 80 +/- 11.6 (range 40-120) mmHg. RESULTS: Various extra-anatomical
      bypass strategies included left subclavian artery to descending aorta (n = 38),
      ascending aorta to left subclavian artery (n = 3), ascending aorta to descending
      aorta (n = 4), aortic arch to descending aorta (n = 3) and ascending aorta to
      abdominal aorta (n = 5). Graft size (median 18, range 10-26, mm) was chosen
      according to the diameter of the vessel proximal and distal to the planned graft.
      No operative deaths, paraplegia or abdominal malperfusion occurred. The mean
      reduction in systolic blood pressure was 60 +/- 25 mmHg without pressure
      gradients. During a mean follow-up of 18.3 +/- 3.7 years, there were no
      reoperations, graft complications or pseudoaneurysm formation on anastomotic
      sites. Seven (11.6%) patients are on antihypertensive medications. No patient
      presented with claudication nor did anyone experience orthostatic problems from
      the steal phenomenon. CONCLUSIONS: Extra-anatomical bypass is safe, an effective
      technique, and achieves satisfactory long-term results.

PMID- 28498911
TI  - Different Chromatographic Methods for Simultaneous Determination of Mefenamic
      Acid and Two of Its Toxic Impurities.
AB  - Two sensitive, accurate and precise chromatographic methods mentioned as TLC
      densitometric method and RP-HPLC-DAD method, were developed and validated for the
      simultaneous determination of mefenamic acid (MEF) and its two toxic impurities,
      benzoic acid (BA) and 2,3-dimethylaniline (DMA). In the proposed TLC
      densitometric method a developing system consisting of chloroform:acetone:acetic
      acid:ammonia solution(70:30:2:2, v/v/v/v) was used, TLC aluminum plates 60 F254
      was used as a stationary phase and the separated bands were UV-scanned at 225 nm.
      While the proposed RP-HPLC-DAD method depended on chromatographic separation on
      C18 column using 0.05 M KH2PO4 buffer: acetonitrile (40:60, v/v) as a mobile
      phase at constant flow rate of 1 mL/min with UV detection at 225 nm. Linear
      relationships were obtained in the ranges of 0.3-2, 0.3-2 and 0.3-1.8 MUg/band
      (for TLC-densitometric method) and in the ranges of 7-50, 10-50 and 7-50 MUg/mL
      (for HPLC-DAD method) for MEF, BA and DMA, respectively. Factors affecting the
      developed methods have been studied and optimized. Moreover ,the proposed methods
      were successfully applied for determination of the studied drug in its
      pharmaceutical dosage form. The methods showed no significance difference when
      compared with the reported method using F-test and Student's-t test. The low of
      detection and quantization limits of the proposed methods get them suitable for
      quality control and stability studies of MEF in pharmaceutical formulation. The
      developed methods have advantages of being more selective and sensitive than the
      published methods.

PMID- 28498912
TI  - Data Resource Profile: Seeding Success: a cross-sectoral data resource for early
      childhood health and development research in Australian Aboriginal and non
      Aboriginal children.

PMID- 28498914
TI  - Bibliometric analysis and curriculum mapping of travel medicine research.
AB  - Evidence-based travel medicine requires that research priorities reflect the wide
      knowledge base of this discipline. Bibliometric analysis of articles published in
      Journal of Travel Medicine yielded the following results: epidemiology (6%, n =
      105); immunology/vaccinology (8.5%, n = 148); pre-travel assessment/consultation
      (30.5%, n = 533); diseases contracted during travel (48.3%, n = 843); other
      clinical conditions associated with travel (6.8%, n = 119); post-travel
      assessment (5.2%, n = 91) and administrative and general travel medicine issues
      (6%, n = 105).

PMID- 28498915
TI  - Adults of Lasioderma serricorne and Stegobium paniceum (Anobiidae: Coleoptera)
      Are Attracted to Ultraviolet (UV) Over Blue Light LEDs.
AB  - Two species, the cigarette beetle Lasioderma serricorne (F.) and the drugstore
      beetle Stegobium paniceum (L.), are particularly important stored-product pests
      because they damage dry food. A previous study showed that L. serricorne adults
      are attracted more to ultraviolet (UV) and blue light wave ranges more than
      others such as turquoise, green, yellow, red, and warm white. However, the
      previous study did not equalize the amounts of light. The study also evaluated
      the attractiveness by the numbers of L. serricorne individuals that were lured to
      LED lights in a small box in the laboratory. In some storehouses, damage by S.
      paniceum is more serious and establishment of an effective monitoring tool is
      required. Therefore, in the present study, attractions of these beetles to UV and
      blue light traps were compared to develop a tool to monitor the beetle pests.
      First, adult L. serricorne and S. paniceum beetles were provided with UV- and
      blue-LED panels whose light intensities were equalized in the laboratory, and the
      walking and flying paths of each adult were recorded and measured. As a result,
      adults were clearly attracted to the side of UV-LED panel by walking compared to
      the blue one. Second, we compared the numbers of cigarette beetles collected by
      sticky sheets that were set in the back of UV or blue-light LED traps in a real
      storehouse. The results showed that these beetles were significantly more
      attracted to UV than blue-light LED traps, indicating the UV-LED trap is a
      powerful tool to monitor these two pest species.

PMID- 28498913
TI  - The management of menopause in women with a history of endometriosis: a
      systematic review.
AB  - BACKGROUND: Endometriosis is typically regarded as a premenopausal disease,
      resolving after natural or iatrogenic menopause due to declining oestrogen
      levels. Nonetheless, case reports over the years have highlighted the incidence
      of recurrent postmenopausal endometriosis. It is now clear that both recurrence
      and malignant transformation of endometriotic foci can occur in the
      postmenopausal period. Postmenopausal women are commonly treated with hormone
      replacement therapy (HRT) to treat climacteric symptoms and prevent bone loss;
      however, HRT may reactivate endometriosis and stimulate malignant transformation
      in women with a history of endometriosis. Given the uncertain risks of initiating
      HRT, it is difficult to determine the best menopausal management for this group
      of women. OBJECTIVE AND RATIONAL: The aim of this study was to systematically
      review the existing literature on management of menopausal symptoms in women with
      a history of endometriosis. We also aimed to evaluate the published literature on
      the risks associated with HRT in these women, and details regarding optimal
      formulations and timing (i.e. initiation and duration) of HRT. SEARCH METHODS:
      Four electronic databases (MEDLINE via OVID, Embase via OVID, PsycINFO via OVID
      and CINAHL via EbscoHost) were searched from database inception until June 2016,
      using a combination of relevant controlled vocabulary terms and free-text terms
      related to 'menopause' and 'endometriosis'. Inclusion criteria were: menopausal
      women with a history of endometriosis and menopausal treatment including HRT or
      other preparations. Case reports/series, observational studies and clinical
      trials were included. Narrative review articles, organizational guidelines and
      conference abstracts were excluded, as were studies that did not report on any
      form of menopausal management. Articles were assessed for risk of bias and
      quality using GRADE criteria. OUTCOMES: We present a synthesis of the existing
      case reports of endometriosis recurrence or malignant transformation in women
      undergoing treatment for menopausal symptoms. We highlight common presenting
      symptoms, potential risk factors and outcomes amongst the studies. Sparse high
      quality evidence was identified, with few observational studies and only two
      randomized controlled trials. Given this paucity of data, no definitive
      conclusions can be drawn concerning risk. WIDER IMPLICATIONS: Due to the lack of
      high-quality studies, it remains unclear how to advise women with a history of
      endometriosis regarding the management of menopausal symptoms. The absolute risk
      of disease recurrence and malignant transformation cannot be quantified, and the
      impact of HRT use on these outcomes is not known. Multicentre randomized trials
      or large observational studies are urgently needed to inform clinicians and
      patients alike.

PMID- 28498916
TI  - Effects of the Activation of Three Major Hepatic Akt Substrates on Glucose
      Metabolism in Male Mice.
AB  - Insulin suppresses glucose output from the liver via Akt activation; however,
      which substrate of Akt plays the major role in transducing this effect is
      unclear. We tested the postnatal expression of Akt-unresponsive, constitutively
      active mutants of three major Akt substrates widely considered to regulate
      glucose metabolism [i.e., FoxO1, PGC1alpha, and glycogen synthase kinase-3beta
      (GSK3beta)] using adenoviral gene delivery to the mouse liver. We performed
      physiological hyperinsulinemic-euglycemic clamp studies using these mice under
      awake and nonrestrained conditions with blood sampling via an arterial catheter.
      Hepatic expression of constitutively active FoxO1 induced significant hepatic and
      systemic insulin resistance. However, neither the expression of constitutively
      active PGC1alpha nor that of GSK3beta significantly changed insulin sensitivity.
      Simultaneous expression of all three mutants together induced no further insulin
      resistance compared with that of the FoxO1 mutant. The glycogen content in the
      liver was significantly reduced by constitutively active GSK3beta expression. In
      cultured hepatocytes, constitutively active PGC1alpha induced markedly stronger
      transcriptional enhancement of gluconeogenic key enzymes than did constitutively
      active FoxO1. From these results, we conclude that FoxO1 has the most prominent
      role in transducing insulin's effect downstream from Akt to suppress hepatic
      glucose output, involving mechanisms independent of the transcriptional
      regulation of key gluconeogenic enzymes.

PMID- 28498917
TI  - The New Genomics: What Molecular Databases Can Tell Us About Human Population
      Variation and Endocrine Disease.
AB  - Major recent advances in genetics and genomics present unique opportunities for
      enhancing our understanding of human physiology and disease predisposition. Here
      I demonstrate how analysis of genomic information can provide new insights into
      endocrine systems, using the human growth hormone (GH) signaling pathway as an
      illustrative example. GH is essential for normal postnatal growth in children,
      and plays important roles in other biological processes throughout life. GH
      actions are mediated by the GH receptor, primarily via the JAK2 protein tyrosine
      kinase and the STAT5B transcription factor, and inactivating mutations in this
      pathway all lead to impaired somatic growth. Variation in GH signaling genes has
      been evaluated using DNA sequence data from the Exome Aggregation Consortium, a
      compendium of information from >60,000 individuals. Results reveal many potential
      missense and other alterations in the coding regions of GH1, GHR, JAK2, and
      STAT5B, with most changes being uncommon. The total number of different alleles
      per gene varied by ~threefold, from 101 for GH1 to 338 for JAK2. Several known
      disease-linked mutations in GH1, GHR, and JAK2 were present but infrequent in the
      population; however, three amino acid changes in GHR were sufficiently prevalent
      (~4% to 44% of chromosomes) to suggest that they are not disease causing.
      Collectively, these data provide new opportunities to understand how genetically
      driven variability in GH signaling and action may modify human physiology and
      disease.

PMID- 28498918
TI  - Expression and Activity of the Small RhoGTPase Cdc42 in Blood Cells of Older
      Adults Are Associated With Age and Cardiovascular Disease.
AB  - The small RhoGTPase Cdc42 is mechanistically linked to aging of multiple tissues
      and to rejuvenation of hematopoietic stem cells in mice. However, data validating
      Cdc42 activity and expression as biomarker for aging in humans are still missing.
      Here, we hypothesized that Cdc42 might serve as a novel biomarker of aging in
      older adults and therefore we determined Cdc42 activity and expression levels in
      peripheral blood cells from a cohort of 196 donors. We investigated the
      association of these parameters with both chronological and biological aging. We
      also tested in this cohort of older adults a recently published algorithm
      determining chronological age based on DNA methylation profiles. A positive
      correlation with chronological age was found for both the level of Cdc42 mRNA and
      the level of active Cdc42 protein (the GTP bound form). Notably, the level of
      Cdc42 mRNA as well as total protein showed a specific strong association to
      cardiovascular disease and Cdc42 mRNA levels also to a history of myocardial
      infarction. In summary, these data validate Cdc42 as a blood biomarker of both
      chronological aging as well as aging-associated diseases like cardiovascular
      disease and myocardial infarction.

PMID- 28498919
TI  - Chemicogenetic Restoration of the Prefrontal Cortex to Amygdala Pathway
      Ameliorates Stress-Induced Deficits.
AB  - Corticosteroid stress hormones exert a profound impact on cognitive and emotional
      processes. Understanding the neuronal circuits that are altered by chronic stress
      is important for counteracting the detrimental effects of stress in a brain
      region- and cell type-specific manner. Using the chemogenetic tool, Designer
      Receptors Exclusively Activated by Designer Drugs (DREADDs), which enables the
      remote, noninvasive and long-lasting modulation of cellular activity and signal
      transduction in discrete neuronal populations in vivo, we sought to identify the
      specific pathways that play an essential role in stress responses. We found that
      prolonged severe stress induced the diminished glutamatergic projection from
      pyramidal neurons in prefrontal cortex (PFC) to GABAergic interneurons in
      basolateral amygdala (BLA), leading to the loss of feedforward inhibition and
      ensuing hyperexcitability of BLA principal neurons, which caused a variety of
      behavioral abnormalities. Activating PFC pyramidal neurons with hM3D(Gq) DREADD
      restored the functional connection between PFC and BLA in stressed animals,
      resulting in the rescue of recognition memory, normalization of locomotor
      activity and reduction of aggressive behaviors. Inhibiting BLA principal neurons
      directly with hM4D(Gi) DREADD also blocked BLA hyperactivity and aggressive
      behaviors in stressed animals. These results have offered an effective avenue to
      counteract the stress-induced disruption of circuitry homeostasis.

PMID- 28498920
TI  - Copy number variation of functional RBMY1 is associated with sperm motility: an
      azoospermia factor-linked candidate for asthenozoospermia.
AB  - STUDY QUESTION: What is the influence of copy number variation (CNV) in
      functional RNA binding motif protein Y-linked family 1 (RBMY1) on spermatogenic
      phenotypes? SUMMARY ANSWER: The RBMY1 functional copy dosage is positively
      correlated with sperm motility, and dosage insufficiency is an independent risk
      factor for asthenozoospermia. WHAT IS KNOWN ALREADY: RBMY1, a multi-copy gene
      expressed exclusively in the adult testis, is one of the most important
      candidates for male infertility in the azoospermia factor (AZF) region of the Y
      chromosome. RBMY1 encodes an RNA-binding protein that serves as a pre-mRNA
      splicing regulator during spermatogenesis, and male mice deficient in Rbmy are
      sterile. STUDY DESIGN, SIZE, DURATION: A total of 3127 adult males were recruited
      from 2009 to 2016; of this group, the dosage of RBMY1 functional copy were
      investigated in 486 fertile males. In the remaining 2641 males with known
      spermatogenesis status, 1070 Y-chromosome haplogroup (Y-hg) O3* or O3e carriers
      without chromosomal aberration or known AZF structure mutations responsible for
      spermatogenic impairment, including 506 men with normozoospermia and 564 men with
      oligozoospermia or/and asthenozoospermia, were screened, and the RBMY1 functional
      copy dosage and copy conversion were determined to explore their associations
      with sperm phenotypes. The correlation between RBMY1 dosage and its mRNA level or
      RBMY1 protein level and the correlation between sperm RBMY1 level and motility
      were analysed in 15 testis tissue samples and eight semen samples. Ten additional
      semen samples were used to confirm the subcellular localization of RBMY1 in
      individual sperm. PARTICIPANTS/MATERIALS, SETTING, METHODS: All the Han
      volunteers donating whole blood, semen and testis tissue were from southwest
      China. RBMY1 copy number, copy conversion, mRNA/protein amount and protein
      location in sperm were detected using the AccuCopy(r) assay method, paralog ratio
      test, quantitative PCR, western blotting and immunofluorescence staining methods,
      respectively. MAIN RESULTS AND THE ROLE OF CHANCE: This study identified Y-hg
      independent CNV of functional RBMY1 in the enrolled population. A difference in
      the distribution of RBMY1 copy number was observed between the group with normal
      sperm motility and the group with asthenozoospermia. A positive correlation
      between the RBMY1 copy dosage and sperm motility was identified, and the males
      with fewer than six copies of RBMY1 showed an elevated risk for asthenozoospermia
      relative to those with six RBMY1 copies, the most common dosage in the
      population. The RBMY1 copy dosage was positively correlated with its mRNA and
      protein level in the testis. Sperm with high motility were found to carry more
      RBMY1 protein than those with relatively low motility. The RBMY1 protein was
      confirmed to predominantly localize in the neck and mid-piece region of sperm as
      well as the principal piece of the sperm tail. Our population study completes a
      chain of evidence suggesting that RBMY1 influences the susceptibility of males to
      asthenozoospermia by modulating sperm motility. LIMITATIONS REASONS FOR CAUTION:
      High sequence similarity between the RBMY1 functional copies and a large number
      of pseudogenes potentially reduces the accuracy of the copy number detection. The
      mechanism underlying the CNV in RBMY1 is still unclear, and the effect of the
      structural variations in the RBMY1 copy cluster on the copy dosage of other
      protein-coding genes located in the region cannot be excluded, which may
      potentially bias our observations. WIDER IMPLICATIONS OF THE FINDINGS:
      Asthenozoospermia is a multi-factor complex disease with a limited number of
      proven susceptibility genes. This study identified a novel genomic candidate
      independently contributing to the condition, enriching our understanding of the
      role of AZF-linked genes in male reproduction. Our finding provides insight into
      the physiological and pathological characteristics of RBMY1 in terms of sperm
      motility, supplies persuasive evidence of the significance of RBMY1 copy number
      analysis in the clinical counselling of male infertility resulting from
      asthenozoospermia. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by
      the National Natural Science Foundation of China (Nos. 81370748 and 30971598).
      The authors have no conflicts of interest.

PMID- 28498921
TI  - A meta-analysis of the use of rifaximin to prevent travellers' diarrhoea.
AB  - Background: Travellers' diarrhoea affects tens of millions of people travelling
      to less developed countries or regions annually. There are positive reports of
      the use of rifaximin, a non-absorbed, gut-selective antibiotic to prevent
      travellers' diarrhoea. This study will critically review and analyse clinical
      trials on the subject. Methods: Using the keywords [diarrhoea OR diarrhoea OR
      travel*] AND [rifaximin OR xifaxan OR xifaxanta OR normix OR rifagut], a
      preliminary search on the PubMed and Ovid databases yielded 411 papers published
      in English between 1 January 1988 and 1 July 2016. Of these, there were only five
      relevant clinical trials. Results: The clinical trials were double-blind, placebo
      controlled, randomized trials with a total of 879 subjects. The meta-analysis
      found significant reduction in risk of travellers' diarrhoea with rifaximin use
      compared to placebo (pooled RR 0.478, 95% CI: 0.375-0.610, and P  < 0.001). For
      the entire travel and follow-up period, the risk of developing travellers'
      diarrhoea was significantly greater in individuals receiving the placebo than
      those receiving rifaximin (daily doses of 400-600 mg). Overall, rifaximin offered
      significant protection rates of 48-72%, with lower protection rates for Asian
      than Latin American countries. In terms of tolerability, similar rates of adverse
      events were reported for the rifaximin and placebo group ( P  > 0.05), with no
      clinically significant or serious adverse events related to rifaximin use.
      Conclusions: There is good evidence supporting the use of rifaximin as a
      chemoprophylactic agent against travellers' diarrhoea, especially in individuals
      who are at high risk of severe complications from acute infectious diarrhoea.
      Rifaximin has an excellent tolerability/safety profile and demonstrated efficacy
      against diarrhoeagenic Escherichia coli and even enteroinvasive bacteria such
      Campylobacter species. Future studies should study the most effective dosing
      regimen for rifaximin chemoprophylaxis, as well as profile local antimicrobial
      resistance/susceptibility data in less developed regions to further guide
      rifaximin use.

PMID- 28498922
TI  - Outpatient vs Inpatient Anterior Cervical Discectomy and Fusion: A Population
      Level Analysis of Outcomes and Cost.
AB  - BACKGROUND: Outpatient anterior cervical discectomy and fusion (ACDF) is a
      promising candidate for US healthcare cost reduction as several studies have
      demonstrated that overall complications are relatively low and early discharge
      can preserve high patient satisfaction, low morbidity, and minimal readmission.
      OBJECTIVE: To compare clinical outcomes and associated costs between inpatient
      and ambulatory setting ACDF. METHODS: Demographics, comorbidities, emergency
      department (ED) visits, readmissions, reoperation rates, and 90-d charges were
      retrospectively analyzed for patients undergoing elective ACDF in California,
      Florida, and New York from 2009 to 2011 in State Inpatient and Ambulatory
      Databases. RESULTS: A total of 3135 ambulatory and 46 996 inpatient ACDFs were
      performed. Mean Charlson comorbidity index, length of stay, and mortality were
      0.2, 0.4 d, and 0% in the ambulatory cohort and 0.4, 1.8 d, and 0.04% for
      inpatients (P < .0001). Ambulatory patients were younger (48.0 vs 53.1) and more
      likely to be Caucasian. One hundred sixty-eight ambulatory patients (5.4%)
      presented to the ED within 30 d (mean 11.3 d), 51 (1.6%) were readmitted, and 5
      (0.2%) underwent reoperation. Among inpatient surgeries, 2607 patients (5.5%)
      presented to the ED within 30 d (mean 9.7 d), 1778 (3.8%) were readmitted (mean
      6.3 d), and 200 (0.4%) underwent reoperation. Higher Charlson comorbidity index
      increased rate of ED visits (ambulatory operating room [OR] 1.285, P < .05;
      inpatient OR 1.289, P < .0001) and readmission (ambulatory OR 1.746, P < .0001;
      inpatient OR 1.685, P < .0001). Overall charges were significantly lower for
      ambulatory ACDFs ($33 362.51 vs $74 667.04; P < .0001). CONCLUSION: ACDF can be
      performed in an ambulatory setting with comparable morbidity and readmission
      rates, and lower costs, to those performed in an inpatient setting.

PMID- 28498923
TI  - Preventive measures for "Pet Friendly" lodging facilities: association of
      Leishmaniasis expansion route in Sao Paulo and preventive measures for regional
      animals displacement.

PMID- 28498924
TI  - Major role of pKpQIL-like plasmids in the early dissemination of KPC-type
      carbapenemases in the UK.
AB  - Objectives: Klebsiella pneumoniae carbapenemase (KPC)-producing
      Enterobacteriaceae were first seen in the UK in 2003 and have been increasingly
      reported since 2010, largely owing to an ongoing outbreak in North-West England.
      We examined the role of clonal spread and plasmid transmission in their
      emergence. Methods: Isolates comprised KPC-positive K. pneumoniae ( n  =   33),
      Escherichia coli ( n  =   7) and Enterobacter spp. ( n  =   4) referred to the
      national reference laboratory between 2008 and 2010 from 17 UK centres, including
      three in North-West England. Isolates were typed by MLST. Plasmids were
      transferred by electroporation and characterized by PCR or sequencing. PCR
      screening assays were developed to distinguish plasmid pKpQIL variants. Results:
      The K. pneumoniae isolates included 10 STs, of which three belonged to clonal
      group (CG) 258. CG258 ( n  =   19) isolates were detected in 13 centres but
      accounted for only 7/19 (36.8%) of those from North-West England. Most KPC
      producers (37/44, 84.1%), including 16/19 CG258 K. pneumoniae , carried bla KPC
      on IncFII K2 plasmids. Sequencing of a subset of these plasmids ( n  =   11)
      revealed similarities with published pKpQIL. One variant, pKpQIL-UK [identified
      in K. pneumoniae CG258 ( n  =   5) and ST468 ( n  =   1) isolates from distinct
      centres] had only a few nucleotide changes from classical pKpQIL, whereas pKpQIL
      D1 ( n  =   1) and pKpQIL-D2 ( n  =   4), from isolates of various species in the
      North-West, harboured large variations, reflecting replacement of the
      partitioning and replication functions and potentially thereby facilitating
      spread. PCR revealed that 36/37 (97.3%) IncFII K2 -type plasmids in KPC-positive
      isolates had pKpQIL markers. Conclusions: pKpQIL-like plasmids played a major
      role in the early dissemination of KPC enzymes in the UK.

PMID- 28498925
TI  - A case report of anaphylaxis to Typhoid Vaccine Live Oral Ty21a (Vivotif).
AB  - Typhoid Vaccine Live Oral Ty21a (Vivotif) is typically well tolerated, and
      adverse events are infrequent and mild. To the best of the authors' knowledge,
      only one prior anaphylactic reaction has previously been reported. We present a
      case of anaphylaxis related to Vivotif, in which a 66-year-old male with no
      medical comorbidities developed anaphylaxis following the third of a four-dose
      course (in the absence of concomitant vaccination administration), which
      consisted of tongue swelling, difficulty breathing, abdominal discomfort and
      rash. He was managed with epinephrine, corticosteroids and antihistamines.

PMID- 28498926
TI  - Categorizing body mass index biases assessment of the association with post
      coronary artery bypass graft mortality.
AB  - OBJECTIVES: The high prevalence of obesity makes accurately estimating the impact
      of anthropometric measures on cardiac surgery outcomes critical. The Society of
      Thoracic Surgeons coronary artery bypass graft (CABG) surgery risk model includes
      body surface area (as a continuous variable, using spline functions), but most
      studies apply various categorizations of body mass index (BMI)-contributing to
      the contradictory published findings. We assessed the association between BMI
      (modelled as a continuous variable without assumptions of linearity) and CABG
      operative mortality and examined the impact of applying previous studies' BMI
      modelling strategies. METHODS: We identified 25 studies investigating the BMI
      operative mortality association: 22 categorized BMI, 2 as a linear continuous
      variable,1 used spline functions. Our cohort of 12 715 consecutive patients
      underwent isolated CABG at 32 cardiac surgery programmes in North Texas from 1
      January 2008-31 December 2012. BMI was modelled using restricted cubic spline
      functions in a propensity-adjusted model (controlling for Society of Thoracic
      Surgeons risk factors) estimating operative mortality. The analysis was repeated
      using each categorization identified and modelling BMI as a linear continuous
      variable. RESULTS: BMI (modelled with a restricted cubic spline) was
      significantly associated with operative mortality (P < 0.0001). Risk was lowest
      for BMI near 30 kg/m2 and highest below 20 kg/m2 and above 40 kg/m2. No
      categorization, nor the linear continuous model, fully captured this association.
      CONCLUSIONS: BMI is strongly associated with CABG operative mortality.
      Categorizing BMI (or assuming a linear relationship) heavily biases estimates of
      its association with post-CABG mortality. In general, smoothing techniques should
      be used for all continuous risk factors to avoid bias.

PMID- 28498927
TI  - Efficacy and safety of carbetocin given as an intravenous bolus compared with
      short infusion for Caesarean section - double-blind, double-dummy, randomized
      controlled non-inferiority trial.
AB  - Background: Carbetocin is a synthetic oxytocin-analogue, which should be
      administered as bolus according to manufacturer's recommendations. A higher speed
      of oxytocin administration leads to increased cardiovascular side-effects. It is
      unclear whether carbetocin administration as short infusion has the same efficacy
      on uterine tone compared with bolus administration and whether haemodynamic
      parameters differ. Methods: In this randomized, double-blind, non-inferiority
      trial, women undergoing planned or unplanned Caesarean section (CS) under
      regional anaesthesia received a bolus and a short infusion, only one of which
      contained carbetocin 100 mcg (double dummy). Obstetricians quantified uterine
      tone two, three, five and 10 min after cord-clamping by manual palpation using a
      linear analogue scale from 0 to 100. We evaluated whether the lower limit of the
      95% CI of the difference in maximum uterine tone within the first five min after
      cord-clamping did not include the pre-specified non-inferiority limit of -10.
      Results: Between December 2014 and November 2015, 69 patients were randomized to
      receive carbetocin as bolus and 71 to receive it as short infusion. Maximal
      uterine tone was 89 in the bolus and 88 in the short infusion group (mean
      difference -1.3, 95% CI -5.7 to 3.1). Bp, calculated blood loss, use of
      additional uterotonics, and side-effects were comparable. Conclusions:
      Administration of carbetocin as short infusion does not compromise uterine tone
      and has similar cardiovascular side-effects as a slow i.v. bolus. In accordance
      with current recommendations for oxytocin, carbetocin can safely be administered
      as short -infusion during planned or unplanned CS. Clinical trial registration:
      ClinicalTrials.gov NCT02221531 and www.kofam.ch SNCTP000001197.

PMID- 28498928
TI  - E2FM: an encrypted and compressed full-text index for collections of genomic
      sequences.
AB  - Motivation: Next Generation Sequencing (NGS) platforms and, more generally, high
      throughput technologies are giving rise to an exponential growth in the size of
      nucleotide sequence databases. Moreover, many emerging applications of nucleotide
      datasets-as those related to personalized medicine-require the compliance with
      regulations about the storage and processing of sensitive data. Results: We have
      designed and carefully engineered E 2 FM -index, a new full-text index in minute
      space which was optimized for compressing and encrypting nucleotide sequence
      collections in FASTA format and for performing fast pattern-search queries. E 2
      FM -index allows to build self-indexes which occupy till to 1/20 of the storage
      required by the input FASTA file, thus permitting to save about 95% of storage
      when indexing collections of highly similar sequences; moreover, it can exactly
      search the built indexes for patterns in times ranging from few milliseconds to a
      few hundreds milliseconds, depending on pattern length. Availability and
      implementation: Source code is available at https://github.com/montecuollo/E2FM .
      Contact: ferdinando.montecuollo@unicampania.it. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 28498929
TI  - Multi-stakeholder perspectives in defining health-services quality in cataract
      care.
AB  - Objective: To develop a method to define a multi-stakeholder perspective on
      health-service quality that enables the expression of differences in
      systematically identified stakeholders' perspectives, and to pilot the approach
      for cataract care. Design: Mixed-method study between 2014 and 2015. Setting:
      Cataract care in the Netherlands. Participants: Stakeholder representatives.
      Intervention(s): We first identified and classified stakeholders using
      stakeholder theory. Participants established a multi-stakeholder perspective on
      quality of cataract care using concept mapping, this yielded a cluster map based
      on multivariate statistical analyses. Consensus-based quality dimensions were
      subsequently defined in a plenary stakeholder session. Main outcome measure(s):
      Stakeholders and multi-stakeholder perspective on health-service quality.
      Results: Our analysis identified seven definitive stakeholders, as follows: the
      Dutch Ophthalmology Society, ophthalmologists, general practitioners,
      optometrists, health insurers, hospitals and private clinics. Patients, as
      dependent stakeholders, were considered to lack power by other stakeholders;
      hence, they were not classified as definitive stakeholders. Overall, 18
      stakeholders representing ophthalmologists, general practitioners, optometrists,
      health insurers, hospitals, private clinics, patients, patient federations and
      the Dutch Healthcare Institute sorted 125 systematically collected indicators
      into the seven following clusters: patient centeredness and accessibility,
      interpersonal conduct and expectations, experienced outcome, clinical outcome,
      process and structure, medical technical acting and safety. Importance scores
      from stakeholders directly involved in the cataract service delivery process
      correlated strongly, as did scores from stakeholders not directly involved in
      this process. Conclusions: Using a case study on cataract care, the proposed
      methods enable different views among stakeholders concerning quality dimensions
      to be systematically revealed, and the stakeholders jointly agreed on these
      dimensions. The methods helped to unify different quality definitions and
      facilitated operationalisation of quality measurement in a way that was accepted
      by relevant stakeholders.

PMID- 28498930
TI  - Risk Factors for Intracranial Aneurysm Rupture: A Systematic Review.
AB  - BACKGROUND: Intracranial aneurysm rupture prediction is poor, with only a few
      risk factors for rupture identified and used in clinical practice. OBJECTIVE: To
      provide an overview of all the risk factors (including genetic, molecular,
      morphological, and hemodynamic factors) that have potential for use in clinical
      practice. METHODS: We systematically searched PubMed and EMBASE and focused on
      factors that can be easily assessed in clinical practice, might be used for
      rupture prediction in clinical practice, and/or are potential targets for further
      research. Studies were categorized according to methodological quality, and a
      meta-analysis was performed, if possible. RESULTS: We included 102 studies
      describing 144 risk factors that fulfilled predefined criteria. There was strong
      evidence for the morphological factors irregular shape (studied in 4 prospective
      cohort studies of high-quality, pooled odds ratio [OR] of 4.8 [95% confidence
      interval 2.7-8.7]), aspect ratio (pooled OR 10.2 [4.3-24.6]), size ratio,
      bottleneck factor, and height-to-width ratio to increase rupture risk. Moderate
      level of evidence was found for presence of contact with the perianeurysmal
      environment (pooled OR 3.5 [1.4-8.4]), unbalanced nature of this contact (pooled
      OR 17.8 [8.3-38.5]), volume-to-ostium ratio, and direction of the aneurysm dome
      (pooled OR 1.5 [1.2-1.9]). CONCLUSION: Irregular aneurysm shape was identified as
      a risk factor with potential for use in clinical practice. The risk factors
      aspect ratio, size ratio, bottleneck factor, height-to-width ratio, contact with
      the perianeurysmal environment, volume-to-ostium ratio, and dome-direction should
      first be confirmed in multivariate analysis and incorporated in prediction
      models.

PMID- 28498932
TI  - From CNTNAP2 to Early Expressive Language in Infancy: The Mediation Role of Rapid
      Auditory Processing.
AB  - Although it is clear that early language acquisition can be a target of CNTNAP2,
      the pathway between gene and language is still largely unknown. This research
      focused on the mediation role of rapid auditory processing (RAP). We tested RAP
      at 6 months of age by the use of event-related potentials, as a mediator between
      common variants of the CNTNAP2 gene (rs7794745 and rs2710102) and 20-month-old
      language outcome in a prospective longitudinal study of 96 Italian infants. The
      mediation model examines the hypothesis that language outcome is explained by a
      sequence of effects involving RAP and CNTNAP2. The ability to discriminate
      spectrotemporally complex auditory frequency changes at 6 months of age mediates
      the contribution of rs2710102 to expressive vocabulary at 20 months. The indirect
      effect revealed that rs2710102 C/C was associated with lower P3 amplitude in the
      right hemisphere, which, in turn, predicted poorer expressive vocabulary at 20
      months of age. These findings add to a growing body of literature implicating RAP
      as a viable marker in genetic studies of language development. The results
      demonstrate a potential developmental cascade of effects, whereby CNTNAP2 drives
      RAP functioning that, in turn, contributes to early expressive outcome.

PMID- 28498931
TI  - Protective effects of hot spring water drinking and radon inhalation on ethanol
      induced gastric mucosal injury in mice.
AB  - Radon therapy using radon (222Rn) gas is classified into two types of treatment:
      inhalation of radon gas and drinking water containing radon. Although short- or
      long-term intake of spa water is effective in increasing gastric mucosal blood
      flow, and spa water therapy is useful for treating chronic gastritis and gastric
      ulcer, the underlying mechanisms for and precise effects of radon protection
      against mucosal injury are unclear. In the present study, we examined the
      protective effects of hot spring water drinking and radon inhalation on ethanol
      induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of
      2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The
      activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100
      Bq/l (end point of supplying). Mice were then orally administered ethanol at
      three concentrations. The ulcer index (UI), an indicator of mucosal injury,
      increased in response to the administration of ethanol; however, treatment with
      either radon inhalation or hot spring water inhibited the elevation in the UI due
      to ethanol. Although no significant differences in antioxidative enzymes were
      observed between the radon-treated groups and the non-treated control groups,
      lipid peroxide levels were significantly lower in the stomachs of mice pre
      treated with radon or hot spring water. These results suggest that hot spring
      water drinking and radon inhalation inhibit ethanol-induced gastric mucosal
      injury.

PMID- 28498933
TI  - Preliminary evaluation of discomfort glare from organic light-emitting diode and
      edge-lit light-emitting diode lighting panels.
AB  - The organic light-emitting diode (OLED) is an area light source, and its primary
      competing technology is the edge-lit light-emitting diode (LED) panel. Both
      technologies are similar in shape and appearance, but there is little
      understanding of how people perceive discomfort glare (DG) from area sources. The
      objective of this study was to evaluate the DG of these two technologies under
      similar operating conditions. Additionally, two existing DG models were compared
      to evaluate the correlation between predicted values and observed values. In an
      earlier study, we found no statistically significant difference in human response
      in terms of DG between OLED and edge-lit LED panels when the two sources produced
      the same luminous stimulus. The range of testing stimulus was expanded to test
      different panel luminances at three background illuminations. The results showed
      no difference in perceived glare between the panels, and, as the background
      illumination increased, the perceived glare decreased. In other words, both
      appeared equally glary beyond a certain luminance and background illumination. We
      then compared two existing glare models with the observed values and found that
      one model showed a good estimation of how humans perceive DG. That model was
      further modified to increase its power.

PMID- 28498935
TI  - The association of changes in DNA methylation with temperature-dependent sex
      determination in cucumber.
AB  - Cucumber (Cucumis sativus L.) is characterized by its diverse and flexible sexual
      types. Here, we evaluated the effect of low temperature (LT) exposure on cucumber
      femaleness under short-day conditions. Shoot apices were subjected to whole
      genome bisulfate sequencing (WGBS), mRNA-seq, and sRNA-seq. The results showed
      that temperature had a substantial and global impact on transposable element (TE)
      related small RNA-directed DNA methylation (RdDM) mechanisms, resulting in large
      amounts of CHH-type cytosine demethylation. In the cucumber genome, TEs are
      common in regions near genes that are also subject to DNA demethylation. TE-gene
      interactions showed very strong reactions to LT treatment, as nearly 80% of the
      differentially methylated regions (DMRs) were distributed in genic regions.
      Demethylation near genes led to the co-ordinated expression of genes and TEs.
      More importantly, genome-wide de novo methylation changes also resulted in small
      amounts of CG- and CHG-type DMRs. Methylation changes in CG-DMRs located <600 bp
      from the transcription start and end sites (TSSs/TESs) negatively correlated with
      transcription changes in differentially expressed genes (DEGs), probably
      indicating epiregulation. Ethylene is called the 'sex hormone' of cucumbers. We
      observed the up-regulation of ethylene biosynthesis-related CsACO3 and the down
      regulation of an Arabidopsis RAP2.4-like ethylene-responsive (AP2/ERF)
      transcription factor, demonstrating the inferred epiregulation. Our study
      characterized the response of the apex methylome to LT and predicted the possible
      epiregulation of temperature-dependent sex determination (TSD) in cucumber.

PMID- 28498934
TI  - Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision
      Medicine: Why and How.
AB  - Implications: This article outlines a framework for the consistent integration of
      biological data/samples into smoking cessation pharmacotherapy trials, aligned
      with the objectives of the recently unveiled Precision Medicine Initiative. Our
      goal is to encourage and provide support for treatment researchers to consider
      biosample collection and genotyping their existing samples as well as integrating
      genetic analyses into their study design in order to realize precision medicine
      in treatment of nicotine dependence.

PMID- 28498936
TI  - A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic Acid in Adult Patients
      Undergoing Resection of a Newly Diagnosed or Recurrent High-Grade Glioma.
AB  - BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin
      fluorescence for the resection of high-grade gliomas is well documented. This
      drug has received regulatory approval in Europe but awaits approval in the United
      States. OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5
      ALA used for enhanced intraoperative visualization of malignant brain tumors,
      reported from a single medical center in the United States. METHODS: Prior to
      craniotomy for resection of a presumed high-grade glioma, individuals were given
      oral 5-ALA as part of a rapid dose-escalation scheme. At least 3 patients were
      selected for each dose level from 10 to 50 mg/kg in 10 mg/kg increments. Adverse
      events, intensity of tumor fluorescence, and results of biopsies in areas of
      tumor and the tumor bed under white light and deep blue light were recorded.
      RESULTS: A total of 19 patients were studied in this phase 1 study. Serious
      adverse events were unrelated to the ingestion of 5-ALA. At the highest dose
      level studied (50 mg/kg), 2 out of 6 patients were observed to have transient
      dermatologic redness and peeling. These were grade 1 adverse events, which were
      not serious enough to be dose limiting. Patients at higher dose levels (>40
      mg/kg) were more likely to have strong tumor fluorescence. There were no
      instances of false positive fluorescence. CONCLUSION: The use of 5-ALA for brain
      tumor fluorescence is safe and effective to a dose of 50 mg/kg. Dose-limiting
      toxicity was not reached in this study.

PMID- 28498937
TI  - The Prevalence of Anosmia and Associated Factors Among U.S. Black and White Older
      Adults.
AB  - Background: Olfactory impairment is common among older adults; however, data are
      largely limited to whites. Methods: We conducted pooled analyses of two community
      based studies: the Atherosclerosis Risk in Communities study (ARIC, 1,398 blacks
      and 4,665 whites), and the Health, Aging, and Body Composition study (Health ABC,
      958 blacks and 1,536 whites) to determine the prevalence of anosmia and
      associated factors for black and white older adults in the United States.
      Results: The overall prevalence of anosmia was 22.3% among blacks and 10.4% among
      whites. Blacks had a markedly higher odds of anosmia compared to whites in age
      and sex adjusted analyses (odds ratio [OR] 2.96, 95% confidence interval [CI] =
      2.59-3.38). In both blacks and whites, higher anosmia prevalence was associated
      with older age and male sex. The highest prevalence was found in black men 85
      years or older (58.3%), and the lowest in white women aged 65-69 years (2.4%).
      Higher education level, lower cognitive score, ApoE epsilon4, daytime sleepiness,
      poorer general health status, lower body mass index, and Parkinson disease were
      associated with higher prevalence of anosmia in one or both races. However, the
      racial difference in anosmia remained statistically significant after adjusting
      for these factors (fully adjusted OR = 1.76, 95%CI: 1.50-2.07). Results were
      comparable between the two cohorts. Discussion: Anosmia is common in older
      adults, particularly among blacks. Further studies are needed to identify risk
      factors for anosmia and to investigate racial disparities in this sensory
      deficit.

PMID- 28498938
TI  - Healthcare Resource Utilization and Patient-Reported Outcomes Following Elective
      Surgery for Intradural Extramedullary Spinal Tumors.
AB  - BACKGROUND: Healthcare resource utilization and patient-reported outcomes (PROs)
      for intradural extramedullary (IDEM) spine tumors are not well reported.
      OBJECTIVE: To analyze the PROs, costs, and resource utilization 1 year following
      surgical resection of IDEM tumors. METHODS: Patients undergoing elective spine
      surgery for IDEM tumors and enrolled in a single-center, prospective,
      longitudinal registry were analyzed. Baseline and postoperative 1-year PROs were
      recorded. One-year spine-related direct and indirect healthcare resource
      utilization was assessed. One-year resource use was multiplied by unit costs
      based on Medicare national payment amounts (direct cost). Patient and caregiver
      workday losses were multiplied by the self-reported gross-of-tax wage rate
      (indirect cost). RESULTS: A total of 38 IDEM tumor patients were included in this
      analysis. There was significant improvement in quality of life (EuroQol-5D),
      disability (Oswestry and Neck Disability Indices), pain (Numeric rating scale
      pain scores for back/neck pain and leg/arm pain), and general physical and mental
      health (Short-form-12 health survey, physical and mental component scores) in
      both groups 1 year after surgery (P < .0001). Eighty-seven percent (n = 33) of
      patients were satisfied with surgery. The 1-year postdischarge resource
      utilization including healthcare visits, medication, and diagnostic cost was
      $4111 +/- $3596. The mean total direct cost was $23 717 +/- $7412 and indirect
      cost was $5544 +/- $4336, resulting in total 1-year cost $29 177 +/- $9314.
      CONCLUSION: Surgical resection of the IDEM provides improvement in patient
      reported quality of life, disability, pain, general health, and satisfaction at 1
      year following surgery. Furthermore, we report the granular costs of surgical
      resection and healthcare resource utilization in this population.

PMID- 28498939
TI  - Carbon utilization profiles of river bacterial strains facing sole carbon sources
      suggest metabolic interactions.
AB  - Microbial communities play a key role in water self-purification. They are
      primary drivers of biogenic element cycles and ecosystem processes. However,
      these communities remain largely uncharacterized. In order to understand the
      diversity-heterotrophic activity relationship facing sole carbon sources, we
      assembled a synthetic community composed of 20 'typical' freshwater bacterial
      species mainly isolated from the Zenne River (Belgium). The carbon source
      utilization profiles of each individual strain and of the mixed community were
      measured in Biolog Phenotype MicroArrays PM1 and PM2A microplates that allowed
      testing 190 different carbon sources. Our results strongly suggest interactions
      occurring between our planktonic strains as our synthetic community showed
      metabolic properties that were not displayed by its single components. Finally,
      the catabolic performances of the synthetic community and a natural community
      from the same sampling site were compared. The synthetic community behaved like
      the natural one and was therefore representative of the latter in regard to
      carbon source consumption.

PMID- 28498941
TI  - Erratum.

PMID- 28498940
TI  - Contribution of aerobic anoxygenic phototrophic bacteria to total organic carbon
      pool in aquatic system of subtropical karst catchments, Southwest China: evidence
      from hydrochemical and microbiological study.
AB  - Aerobic anoxygenic phototrophic bacteria may play a particular role in carbon
      cycling of aquatic systems. However, little is known about the interaction
      between aerobic anoxygenic phototrophic bacteria and hydrochemistry in
      groundwater-surface water exchange systems of subtropical karst catchments. We
      carried out a detailed study on the abundance of aerobic anoxygenic phototrophic
      bacteria and bacterioplankton, hydrochemistry and taxonomy of bacterioplankton in
      the Maocun watershed, Southwest China, an area with karst geological background.
      Our results revealed that bacteria are the important contributors to total
      organic carbon source/sequestration in the groundwater-surface water of this
      area. The aerobic anoxygenic phototrophic bacteria, including beta
      Proteobacteria, also appear in the studied water system. In addition to that, the
      genus Polynucleobacter of the phototropic beta-Proteobacteria shows a close link
      with those sampling sites by presenting bacterial origin organic carbon on CCA
      biplot and is found to be positively correlated with total nitrogen, dissolved
      oxygen and pH (r = 0.860, 0.747 and 0.813, respectively) in the Maocun watershed.
      The results suggest that Polynucleobacter might be involved in the production of
      organic carbon and might act as the negative feedback on global warming.

PMID- 28498942
TI  - Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year
      randomized clinical trial with 4000 IU vitamin D daily.
AB  - Aims: Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated
      with a nonlinear increase in mortality risk. Such 25OHD levels are common in
      heart failure (HF). We therefore examined whether oral vitamin D supplementation
      reduces mortality in patients with advanced HF. Methods and results: Four hundred
      HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU
      vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause
      mortality. Key secondary outcome measures included hospitalization,
      resuscitation, mechanical circulatory support (MCS) implant, high urgent listing
      for heart transplantation, heart transplantation, and hypercalcaemia. Initial
      25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients
      assigned to placebo and plateaued around 100 nmol/L in patients assigned to
      vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n
      = 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence
      interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however
      greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n =
      15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints
      were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10)
      and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192).
      Conclusion: A daily vitamin D dose of 4000 IU did not reduce mortality in
      patients with advanced HF but was associated with a greater need for MCS
      implants. Data indicate caution regarding long-term supplementation with
      moderately high vitamin D doses. Trial Registration Information:
      clinicaltrials.gov Idenitfier: NCT01326650.

PMID- 28498944
TI  - Assessment of standard laboratory tests and rotational thromboelastometry for the
      prediction of postoperative bleeding in liver transplantation.
AB  - Background: Perioperative bleeding remains a major challenge in liver
      transplantation. We aimed to compare standard laboratory tests with
      thromboelastometry (ROTEM (r) ) with regard to their ability to predict
      postoperative non-surgical bleeding. Methods: Data from 243 adult liver
      transplant recipients from January 2012 to May 2014 were evaluated
      retrospectively. Upon admission to the intensive care unit, coagulation status
      was assessed using standard laboratory tests [prothrombin time (PT), activated
      partial thromboplastin time (aPTT), fibrinogen concentration, and platelet count]
      and ROTEM (r) whole blood coagulation assays. Bleeding was defined as transfusion
      of >= 3 units of red blood cells or reoperation for non-surgical bleeding within
      48 h after transplantation. Coagulation test results were analysed using receiver
      operating characteristics (ROC) in order to identify variables predictive of
      postoperative bleeding. Coagulation management was based on ROTEM (r) -guided
      factor concentrate treatment. Results: The overall incidence of bleeding was
      12.3% ( n =30). Twenty-three (9.5%) patients underwent reoperation and seven
      (2.9%) received >=3 units of red blood cells and non-operative management.
      Standard laboratory tests predictive of postoperative bleeding were aPTT and PT
      [area under the ROC curve (AUC) 0.688 and 0.623, respectively]. Tests predictive
      of bleeding with ROTEM (r) were CT EXTEM , CFT INTEM , A10 FIBTEM , and MCF
      FIBTEM , with AUCs of 0.682, 0.615, 0.615, and 0.611, respectively. Fibrinogen
      concentration, platelet count, and other ROTEM (r) variables failed to
      demonstrate predictive value for postoperative bleeding (AUC <0.6). Dialysis
      dependent kidney failure, 30 day mortality, and median model for endstage liver
      disease score were all significantly higher in bleeding patients. Conclusions:
      Although both postoperative standard laboratory tests and ROTEM (r) assays could
      identify patients at risk for postoperative bleeding, ROTEM (r) assays
      demonstrated a greater predictive value for impaired fibrinogen polymerization
      related coagulopathy.

PMID- 28498943
TI  - Mycobacterium tuberculosis Whole Genome Sequences From Southern India Suggest
      Novel Resistance Mechanisms and the Need for Region-Specific Diagnostics.
AB  - Background.: India is home to 25% of all tuberculosis cases and the second
      highest number of multidrug resistant cases worldwide. However, little is known
      about the genetic diversity and resistance determinants of Indian Mycobacterium
      tuberculosis, particularly for the primary lineages found in India, lineages 1
      and 3. Methods.: We whole genome sequenced 223 randomly selected M. tuberculosis
      strains from 196 patients within the Tiruvallur and Madurai districts of Tamil
      Nadu in Southern India. Using comparative genomics, we examined genetic
      diversity, transmission patterns, and evolution of resistance. Results.: Genomic
      analyses revealed (11) prevalence of strains from lineages 1 and 3, (11) recent
      transmission of strains among patients from the same treatment centers, (11)
      emergence of drug resistance within patients over time, (11) resistance gained in
      an order typical of strains from different lineages and geographies, (11)
      underperformance of known resistance-conferring mutations to explain phenotypic
      resistance in Indian strains relative to studies focused on other geographies,
      and (11) the possibility that resistance arose through mutations not previously
      implicated in resistance, or through infections with multiple strains that
      confound genotype-based prediction of resistance. Conclusions.: In addition to
      substantially expanding the genomic perspectives of lineages 1 and 3, sequencing
      and analysis of M. tuberculosis whole genomes from Southern India highlight
      challenges of infection control and rapid diagnosis of resistant tuberculosis
      using current technologies. Further studies are needed to fully explore the
      complement of diversity and resistance determinants within endemic M.
      tuberculosis populations.

PMID- 28498945
TI  - Conversion after off-pump coronary artery bypass grafting: where are the quality
      markers?

PMID- 28498948
TI  - Community composition and assembly processes of the free-living and particle
      attached bacteria in Taihu Lake.
AB  - Although previous studies have compared the diversity and community composition
      of free-living (FL) and particle-attached (PA) bacterial groups in marine
      ecosystems, few studies have focused on the FL and PA bacterial communities in
      large and shallow eutrophic lakes. Furthermore, the assembly processes of the FL
      and PA bacterial communities have not been investigated. To illustrate the
      differences between PA (>=5.0 MUm) and FL (0.22-5.0 MUm) bacterial communities,
      samples were collected from 13 different sites in Taihu Lake, China. A higher
      diversity of the PA bacterial group than that of the FL group was observed, and
      significant differences in bacterial community composition between FL and PA
      groups were found (analysis of similarity, R = 0.2425, P < 0.001). Moreover, the
      two groups exhibited different relationships with environmental factors and
      geographic distance. Environmental factors played more important roles in
      affecting the FL bacterial community. A deterministic process was found as the
      primary factor driving the community of FL bacteria in Taihu Lake. However, the
      PA bacterial group was characterized by insignificant results of partial Mantel
      tests, which indicated that the community assembly was controlled by unknown
      processes.

PMID- 28498947
TI  - Aminobacter sp. MSH1 invades sand filter community biofilms while retaining 2,6
      dichlorobenzamide degradation functionality under C- and N-limiting conditions.
AB  - Aminobacter sp. MSH1 is of interest for bioaugmentation of biofiltration units in
      drinking water treatment plants (DWTPs) due to its ability to degrade the
      groundwater micropollutant 2,6-dichlorobenzamide (BAM). Using a continuous flow
      chamber biofilm model, MSH1 was previously shown to colonize surfaces and degrade
      BAM at trace concentrations as low as 1 MUg/L under the oligotrophic conditions
      found in DWTPs. In DWTP filtration units, MSH1 has to compete with the resident
      biofilm microbiota for space and nutrients. Using the same model, we examined how
      a sand filter community (SFC) affects MSH1's BAM-degrading activity and biofilm
      formation under C- and N-limiting conditions when fed with trace concentrations
      of BAM. MSH1 was inoculated simultaneously with the SFC (co-colonization mode) or
      after the SFC formed a biofilm (invasion mode). MSH1 successfully established in
      the SFC biofilm showing growth and activity. In co-colonization mode, MSH1
      decreased in number in the presence of the SFC and formed isolated colonies,
      while specific BAM-degradation activity increased. In the invasion mode, MSH1
      also decreased in numbers in the presence of the SFC but formed mixed colonies,
      while specific BAM degradation was unaffected. Our results show that MSH1 invades
      and performs successfully in an SFC biofilm under the oligotrophic conditions of
      DWTPs.

PMID- 28498946
TI  - Overexpression of Rev1 promotes the development of carcinogen-induced intestinal
      adenomas via accumulation of point mutation and suppression of apoptosis
      proportionally to the Rev1 expression level.
AB  - Cancer development often involves mutagenic replication of damaged DNA by the
      error-prone translesion synthesis (TLS) pathway. Aberrant activation of this
      pathway plays a role in tumorigenesis by promoting genetic mutations. Rev1
      controls the function of the TLS pathway, and Rev1 expression levels are
      associated with DNA damage induced cytotoxicity and mutagenicity. However, it
      remains unclear whether deregulated Rev1 expression triggers or promotes
      tumorigenesis in vivo. In this study, we generated a novel Rev1-overexpressing
      transgenic (Tg) mouse and characterized its susceptibility to tumorigenesis.
      Using a small intestinal tumor model induced by N-methyl-N-nitrosourea (MNU), we
      found that transgenic expression of Rev1 accelerated intestinal adenoma
      development in proportion to the Rev1 expression level; however, overexpression
      of Rev1 alone did not cause spontaneous development of intestinal adenomas. In
      Rev1 Tg mice, MNU-induced mutagenesis was elevated, whereas apoptosis was
      suppressed. The effects of hREV1 expression levels on the cytotoxicity and
      mutagenicity of MNU were confirmed in the human cancer cell line HT1080. These
      data indicate that dysregulation of cellular Rev1 levels leads to the
      accumulation of mutations and suppression of cell death, which accelerates the
      tumorigenic activities of DNA-damaging agents.

PMID- 28498949
TI  - Proteolytic cleavage is required for functional neuroligin 2 maturation and
      trafficking in Drosophila.
AB  - Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential
      roles in synapse development and function. Genetic mutations in neuroligin genes
      have been linked with some neurodevelopmental disorders such as autism. These
      mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the
      mechanisms underlying normal Nlg maturation and trafficking have remained largely
      unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes
      proteolytic cleavage in the ER in a variety of Drosophila tissues throughout
      developmental stages. A region encompassing Y642-T698 is required for this
      process. The immature non-cleavable DNlg2 is retained in the ER and non
      functional. The C-terminal fragment of DNlg2 instead of the full-length or non
      cleavable DNlg2 is able to rescue neuromuscular junction defects and GluRIIB
      reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C
      mutation in DNlg2 leads to similar marked defects in DNlg2 proteolytic process
      and ER export, revealing a potential role of the improper Nlg cleavage in autism
      pathogenesis. Collectively, our findings uncover a specific mechanism that
      controls DNlg2 maturation and trafficking via proteolytic cleavage in the ER,
      suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to
      autism disorder.

PMID- 28498950
TI  - IGESS: a statistical approach to integrating individual-level genotype data and
      summary statistics in genome-wide association studies.
AB  - Motivation: Results from genome-wide association studies (GWAS) suggest that a
      complex phenotype is often affected by many variants with small effects, known as
      'polygenicity'. Tens of thousands of samples are often required to ensure
      statistical power of identifying these variants with small effects. However, it
      is often the case that a research group can only get approval for the access to
      individual-level genotype data with a limited sample size (e.g. a few hundreds or
      thousands). Meanwhile, summary statistics generated using single-variant-based
      analysis are becoming publicly available. The sample sizes associated with the
      summary statistics datasets are usually quite large. How to make the most
      efficient use of existing abundant data resources largely remains an open
      question. Results: In this study, we propose a statistical approach, IGESS, to
      increasing statistical power of identifying risk variants and improving accuracy
      of risk prediction by i ntegrating individual level ge notype data and s ummary s
      tatistics. An efficient algorithm based on variational inference is developed to
      handle the genome-wide analysis. Through comprehensive simulation studies, we
      demonstrated the advantages of IGESS over the methods which take either
      individual-level data or summary statistics data as input. We applied IGESS to
      perform integrative analysis of Crohns Disease from WTCCC and summary statistics
      from other studies. IGESS was able to significantly increase the statistical
      power of identifying risk variants and improve the risk prediction accuracy from
      63.2% ( +/-0.4% ) to 69.4% ( +/-0.1% ) using about 240 000 variants. Availability
      and implementation: The IGESS software is available at
      https://github.com/daviddaigithub/IGESS . Contact: zbxu@xjtu.edu.cn or
      xwan@comp.hkbu.edu.hk or eeyang@hkbu.edu.hk. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 28498951
TI  - Single-Target and Multiplex Discrimination of Whiteflies (Hemiptera: Aleyrodidae)
      Bemisia tabaci and Trialeurodes vaporariorum With Modified Priming
      Oligonucleotide Thermodynamics.
AB  - The whitefly species Bemisia tabaci (Gennadius) and Trialeurodes vaporariorum
      (Westwood) are worldwide agricultural pests and virus vectors. Bemisia tabaci, in
      particular, is often transported internationally via trade routes leading to
      potential introductions of exotic whiteflies or plant viruses. Quick
      identification of agriculturally important whiteflies can facilitate
      interventions that prevent these cross-border introductions. Polymerase chain
      reaction (PCR) primers were designed to amplify the mitochondrial cytochrome
      oxidase I gene (mtCOI) sequence of members of the B. tabaci complex, MEAM1, MED,
      and NW, and T. vaporariorum. Primers incorporated an A/T-rich overhang sequence
      at the 5' terminus (5' flap) to test for increased primer sensitivity and assay
      efficiency. Single-target and multiplex endpoint PCR assays with the eight primer
      sets were performed using genomic DNA template extracted from individual adult
      whiteflies. Resultant PCR amplicons obtained for B. tabaci MEAM1, MED, and NW,
      and T. vaporariorum primers with the 5' flap were 559-, 717-, 353-, and 258-bp,
      respectively, and without the 5' flap were 550-, 712-, 329-, and 252-bp in
      length, respectively. In single-target and multiplex reactions, specific
      amplification was achieved using both the unmodified and 5' flap-modified
      primers. Sequencing and phylogenetic analysis confirmed primer-target
      amplification specificity. Using these primer sets in single-target or multiplex
      PCR allows for quick discrimination and specific identification of B. tabaci
      complex members and T. vaporariorum, and the addition of 5'A/T-rich overhang
      sequences increases the sensitivity and amplification of some primer sets.

PMID- 28498952
TI  - Virtual virus, a semester-long interdisciplinary project on the crossroads of
      creativity and knowledge integration.
AB  - Virtual virus is a semester-long interdisciplinary project offered as part of
      upper level elective course in virology. Students are challenged to apply key
      concepts from multiple biological sub-disciplines to 'synthesize' a plausible
      virtual virus. The project is executed as a scaffolded series of hands-on
      sessions and mini-projects that are integrated into continuous story leading to
      mock conference presentation and comprehensive report modeling article
      publication. It complements classroom instruction helping students to meet
      overarching learning targets traditionally associated undergraduate virology
      courses such as viral structure and function, mode of viral propagation and flow
      of genetic information and virus/host interactions on the cellular and organismal
      level. Formal instructor and informal peer feedback were used as tools to prompt
      reflection and guide revisions of the final report. Student learning gains and
      attitudes toward the approach were studied by evaluating project work product and
      end of the semester survey. Outcome analysis demonstrated that students exit the
      course with elaborated conceptual understanding of viruses and ownership of their
      work. The project can be viewed as an approach to model the process of scientific
      discovery in fast-forward mode by combining active learning, creativity and
      problem solving to assemble and communicate a virtual virus story.

PMID- 28498955
TI  - Transcatheter transapical left ventricle remodelling in ischaemic cardiomyopathy
      with apical aneurysm using 3rd generation 3D cardiac computed tomography fusion
      imaging.

PMID- 28498953
TI  - Pathological Role of Anti-CD4 Antibodies in HIV-Infected Immunologic
      Nonresponders Receiving Virus-Suppressive Antiretroviral Therapy.
AB  - Increased mortality and morbidity occur among human immunodeficiency virus (HIV)
      infected patients in whom CD4+ T-cell counts do not increase despite viral
      suppression with antiretroviral therapy (ART). Here we identified an underlying
      mechanism. Significantly elevated plasma levels of anti-CD4 immunoglobulin G
      (IgG) were found in HIV-positive immunologic nonresponders (ie, HIV-positive
      individuals with CD4+ T-cell counts of <=350 cells/MUL), compared with levels in
      HIV-positive immunologic responders (ie, HIV-positive individuals with CD4+ T
      cell counts of >=500 cells/MUL) and healthy controls. Higher plasma level of anti
      CD4 IgG correlated with blunted CD4+ T-cell recovery. Furthermore, purified anti
      CD4 IgG from HIV-positive immunologic nonresponders induced natural killer (NK)
      cell-dependent CD4+ T-cell cytolysis and apoptosis through antibody-dependent
      cell-mediated cytotoxicity (ADCC) in vitro. We also found that anti-CD4 IgG
      mediated ADCC exerts greater apoptosis of naive CD4+ T cells relative to memory
      CD4+ T cells. Consistently, increased frequencies of CD107a+ NK cells and
      profound decreases of naive CD4+ T cells were observed in immunologic
      nonresponders as compared to responders and healthy controls ex vivo. These data
      indicate that autoreactive anti-CD4 IgG may play an important role in blunted
      CD4+ T-cell reconstitution despite effective ART.

PMID- 28498954
TI  - Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.
AB  - Over the last decade, there has been a growing appreciation of the importance of
      identifying and treating cognitive impairment associated with bipolar disorder,
      since it persists in remission periods. Evidence indicates that neurocognitive
      dysfunction may significantly influence patients' psychosocial outcomes. An ever
      increasing body of research seeks to achieve a better understanding of potential
      moderators contributing to cognitive impairment in bipolar disorder in order to
      develop prevention strategies and effective treatments. This review provides an
      overview of the available data from studies examining treatments for cognitive
      dysfunction in bipolar disorder as well as potential novel treatments, from both
      pharmacological and psychological perspectives. All these data encourage the
      development of further studies to find effective strategies to prevent and treat
      cognitive impairment associated with bipolar disorder. These efforts may
      ultimately lead to an improvement of psychosocial functioning in these patients.

PMID- 28498957
TI  - Global Tactile Coding in Rat Barrel Cortex in the Absence of Local Cues.
AB  - Although whisker-related perception is based predominantly on local, near
      instantaneous coding, global, intensive coding, which integrates the vibrotactile
      signal over time, has also been shown to play a role given appropriate behavioral
      conditions. Here, we study global coding in isolation by studying head-fixed rats
      that identified pulsatile stimuli differing in pulse frequency but not in pulse
      waveforms, thus abolishing perception based on local coding. We quantified time
      locking and spike counts as likely variables underpinning the 2 coding schemes.
      Both neurometric variables contained substantial stimulus information, carried
      even by spikes of single barrel cortex neurons. To elucidate which type of
      information is actually used by the rats, we systematically compared psychometric
      with neurometric sensitivity based on the 2 coding schemes. Neurometric
      performance was calculated by using a population-encoding model incorporating the
      properties of our recorded neuron sample. We found that sensitivity calculated
      from spike counts sampled over long periods (>1 s) matched the performance of
      rats better than the one carried by spikes time-locked to the stimulus. We
      conclude that spike counts are more relevant to tactile perception when
      instantaneous kinematic parameters are not available.

PMID- 28498956
TI  - The Lateral Temporal Lobe in Early Human Life.
AB  - Abnormalities of lateral temporal lobe development are associated with a spectrum
      of genetic and environmental pathologic processes, but more normative data are
      needed for a better understanding of gyrification in this brain region. Here, we
      begin to establish guidelines for the analysis of the lateral temporal lobe in
      humans in early life. We present quantitative methods for measuring gyrification
      at autopsy using photographs of the gross brain and simple computer-based
      quantitative tools in a cohort of 28 brains ranging in age from 27 to 70
      postconceptional weeks (end of infancy). We provide normative ranges for
      different indices of gyrification and identify a constellation of qualitative
      features that should also be considered in these analyses. The ratio of the
      temporal area to the whole brain area increased dramatically in the second half
      of gestation, but then decelerated after birth before increasing linearly around
      50 postconceptional weeks. Tertiary gyrification continued beyond birth in a
      linear process through infancy with considerable variation in patterns. Analysis
      of 2 brains with gyral disorders of the lateral temporal lobe demonstrated proof
      of-principle that the proposed methods are of diagnostic value. These guidelines
      are proposed for assessments of temporal lobe pathology in pediatric brains in
      early life.

PMID- 28498958
TI  - compleXView: a server for the interpretation of protein abundance and
      connectivity information to identify protein complexes.
AB  - The molecular understanding of cellular processes requires the identification and
      characterization of the involved protein complexes. Affinity-purification and
      mass spectrometric analysis (AP-MS) are performed on a routine basis to detect
      proteins assembled in complexes. In particular, protein abundances obtained by
      quantitative mass spectrometry and direct protein contacts detected by
      crosslinking and mass spectrometry (XL-MS) provide complementary datasets for
      revealing the composition, topology and interactions of modules in a protein
      network. Here, we aim to combine quantitative and connectivity information by a
      webserver tool in order to infer protein complexes. In a first step, modeling
      protein abundances and functional annotations from Gene Ontology (GO) results in
      a network which, in a second step, is integrated with connectivity data from XL
      MS analysis in order to complement and validate the protein complexes in the
      network. The output of our integrative approach is a quantitative protein
      interaction map which is supplemented with topological information of the
      detected protein complexes. compleXView is built up by two independent modules
      which are dedicated to the analysis of label-free AP-MS data and to the
      visualization of the detected complexes in a network together with crosslink
      derived distance restraints. compleXView is available to all users without login
      requirements at http://xvis.genzentrum.lmu.de/compleXView.

PMID- 28498959
TI  - Pan-American Similarities in Genetic Structures of Helicoverpa armigera and
      Helicoverpa zea (Lepidoptera: Noctuidae) With Implications for Hybridization.
AB  - The genus Helicoverpa (Lepidoptera: Noctuidae) includes phytophagous and
      polyphagous agricultural insect pests. In the Americas, a native pest,
      Helicoverpa zea (Boddie), and an invasive pest, Helicoverpa armigera (Hubner),
      are causing severe damage in vegetable and agronomic crops. The population
      structure of both species in South America is poorly understood, and the
      phylogenetic relatedness of H. armigera and H. zea suggests natural interspecific
      gene flow between these species. Using microsatellite loci, we investigated: 1)
      the genetic diversity and gene flow of H. armigera specimens from Brazil; 2) the
      genetic diversity and gene flow between H. zea specimens from Brazil and the
      United States; and 3) the possibility of interspecific gene flow and the
      frequency of putative hybrids in Brazil. We detected high intraspecific gene flow
      among populations collected in the same country. However, there is a geographic
      limit to gene flow among H. zea individuals from South and North America.
      Pairwise Fst and private alleles showed that H. armigera is more similar to H.
      zea from Brazil than H. zea from the United States. A comparative STRUCTURE
      analysis suggests natural hybridization between H. armigera and H. zea in Brazil.
      High gene flow and natural hybridization are key traits to population adaptation
      in new and disturbed environments, which can influence the management of these
      pests in the American continent.

PMID- 28498960
TI  - Which is worse? Comparison of ART outcome between women with primary or recurrent
      endometriomas.
AB  - STUDY QUESTION: Are live birth rates (LBR) different after ART cycles between
      women with primary or recurrent endometrioma? SUMMARY ANSWER: Women with
      recurrent endometrioma have similar LBR as compared to patients with primary
      endometrioma. WHAT IS ALREADY KNOWN: Recurrence rate can be as high as 29% after
      endometrioma excision. Prior studies on management of endometrioma before ART
      involve primary endometriomas. There is limited information regarding the
      prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION: A
      multicenter retrospective cohort study, including 76 women with primary and 82
      women with recurrent endometriomas treated at the participating centers over a 6
      year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma
      who underwent ART at three academic ART centers. Couples with another indication
      for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Female age, median
      number of prior failed ART cycles, proportion of patients with bilateral
      endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total
      gonadotropin consumption were similar between the study groups. Numbers of
      metaphase two oocytes (5 versus 6), number of embryos transferred, and the
      proportion of patients undergoing blastocyst transfer were similar across the
      study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference
      2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute
      difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent
      and primary endometrioma were similar. Comparable success rates were also
      confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P =
      2.3). LIMITATIONS, REASONS FOR CAUTION: The retrospective design has inherent
      limitations. Some women with severely decreased ovarian reserve after primary
      endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS
      OF THE FINDINGS: The management of endometrioma prior to ART is controversial but
      a different management strategy is not required for recurrent endometriomas.
      Since recurrent endometriomas do not have a worse impact on ART outcome than
      primary endometriomas, and repeat surgery has a higher risk for complications,
      conservative management without surgery can be justified. STUDY FUNDING/COMPETING
      INTEREST(S): No funding or competing interests to declare. TRIAL REGISTRATION
      NUMBER: None.

PMID- 28498961
TI  - Range-Wide Snow Leopard Phylogeography Supports Three Subspecies.
AB  - The snow leopard, Panthera uncia, is an elusive high-altitude specialist that
      inhabits vast, inaccessible habitat across Asia. We conducted the first range
      wide genetic assessment of snow leopards based on noninvasive scat surveys.
      Thirty-three microsatellites were genotyped and a total of 683 bp of
      mitochondrial DNA sequenced in 70 individuals. Snow leopards exhibited low
      genetic diversity at microsatellites (AN = 5.8, HO = 0.433, HE = 0.568),
      virtually no mtDNA variation, and underwent a bottleneck in the Holocene (~8000
      years ago) coinciding with increased temperatures, precipitation, and upward
      treeline shift in the Tibetan Plateau. Multiple analyses supported 3 primary
      genetic clusters: (1) Northern (the Altai region), (2) Central (core Himalaya and
      Tibetan Plateau), and (3) Western (Tian Shan, Pamir, trans-Himalaya regions).
      Accordingly, we recognize 3 subspecies, Panthera uncia irbis (Northern group),
      Panthera uncia uncia (Western group), and Panthera uncia uncioides (Central
      group) based upon genetic distinctness, low levels of admixture, unambiguous
      population assignment, and geographic separation. The patterns of variation were
      consistent with desert-basin "barrier effects" of the Gobi isolating the northern
      subspecies (Mongolia), and the trans-Himalaya dividing the central (Qinghai,
      Tibet, Bhutan, and Nepal) and western subspecies (India, Pakistan, Tajikistan,
      and Kyrgyzstan). Hierarchical Bayesian clustering analysis revealed additional
      subdivision into a minimum of 6 proposed management units: western Mongolia,
      southern Mongolia, Tian Shan, Pamir-Himalaya, Tibet-Himalaya, and Qinghai, with
      spatial autocorrelation suggesting potential connectivity by dispersing
      individuals up to ~400 km. We provide a foundation for global conservation of
      snow leopard subspecies, and set the stage for in-depth landscape genetics and
      genomic studies.

PMID- 28498962
TI  - An iterative glycosyltransferase EntS catalyzes transfer and extension of O- and
      S-linked monosaccharide in enterocin 96.
AB  - Glycosyltransferases are essential tools for in vitro-glycoengineering. Bacteria
      harbor an unexplored variety of protein glycosyltransferases. Here, we describe a
      peptide glycosyltransferase (EntS) encoded by ORF0417 of Enterococcus faecalis
      TX0104. EntS di-glycosylates linear peptide of enterocin 96- a known
      antibacterial, in vitro. It is capable of transferring as well as extending the
      glycan onto the peptide in an iterative sequential dissociative manner. It can
      catalyze multiple linkages: Glc/Gal(-O)Ser/Thr, Glc/Gal(-S)Cys and
      Glc/Gal(beta)Glc/Gal(-O/S)Ser/Thr/Cys, in one pot. Using EntS generated
      glycovariants of enterocin 96 peptide, size and identity of the glycan are found
      to influence bioactivity of the peptide. The study identifies EntS as an enzyme
      worth pursuing, for in vitro peptide glycoengineering.

PMID- 28498963
TI  - Hypertension in kidney transplantation is associated with an early renal nerve
      sprouting.
AB  - Background.: Normalization of arterial pressure occurs in just a few patients
      with hypertensive chronic kidney disease undergoing kidney transplantation.
      Hypertension in kidney transplant recipients may be related to multiple factors.
      We aimed to assess whether hypertension in kidney-transplanted patients may be
      linked to reinnervation of renal arteries of the transplanted kidney. Methods.:
      We investigated renal arteries innervation from native and transplanted kidneys
      in three patients 5 months, 2 years and 11 years after transplantation,
      respectively. Four transplanted kidneys from non-hypertensive patients on
      immunosuppressive treatment without evidence of hypertensive arteriolar damage
      were used as controls. Results: . Evidence of nerve sprouting was observed as
      early as 5 months following transplantation, probably originated from ganglions
      of recipient patient located near the arterial anastomosis and was associated
      with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves
      was already complete 2 years after transplantation. Nerve density tended to reach
      values observed in native kidney arteries and was associated with hypertension
      related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an
      immunosuppressive regimen, presented only a modest regeneration of sympathetic
      nerves. Conclusions: . Our results suggest that the considerable increase in
      sympathetic nerves, as found in patients with severe arterial damage, may be
      correlated to hypertension rather than to immunosuppressive therapy, thus
      providing a morphological basis for hypertension recurrence despite renal
      denervation.

PMID- 28498964
TI  - Superior Neuronal Detection of Snakes and Conspecific Faces in the Macaque Medial
      Prefrontal Cortex.
AB  - Snakes and conspecific faces are quickly and efficiently detected in primates.
      Because the medial prefrontal cortex (mPFC) has been implicated in attentional
      allocation to biologically relevant stimuli, we hypothesized that it might also
      be highly responsive to snakes and conspecific faces. In this study, neuronal
      responses in the monkey mPFC were recorded, while monkeys discriminated 8
      categories of visual stimuli. Here, we show that the monkey mPFC neuronal
      responses to snakes and conspecific faces were unique. First, the ratios of the
      neurons that responded strongly to snakes and monkey faces were greater than
      those of the neurons that responded strongly to the other stimuli. Second, mPFC
      neurons responded stronger and faster to snakes and monkey faces than the other
      categories of stimuli. Third, neuronal responses to snakes were unaffected by low
      pass filtering of the images. Finally, activity patterns of responsive mPFC
      neurons discriminated snakes from the other stimuli in the second 50 ms period
      and monkey faces in the third period after stimulus onset. These response
      features indicate that the mPFC processes fast and coarse visual information of
      snakes and monkey faces, and support the hypothesis that snakes and social
      environments have shaped the primate visual system over evolutionary time.

PMID- 28498965
TI  - Detection of Zika virus in a traveller from Vietnam to Japan.
AB  - We report an imported case of Zika fever in a traveller from Vietnam. Zika virus
      (ZIKV) is currently widespread in Vietnam. Ongoing transmission of ZIKV has been
      reported in Southeast Asia, and with frequent travel between neighbouring
      regions, careful surveillance for imported cases is needed.

PMID- 28498966
TI  - GenProBiS: web server for mapping of sequence variants to protein binding sites.
AB  - Discovery of potentially deleterious sequence variants is important and has wide
      implications for research and generation of new hypotheses in human and
      veterinary medicine, and drug discovery. The GenProBiS web server maps sequence
      variants to protein structures from the Protein Data Bank (PDB), and further to
      protein-protein, protein-nucleic acid, protein-compound, and protein-metal ion
      binding sites. The concept of a protein-compound binding site is understood in
      the broadest sense, which includes glycosylation and other post-translational
      modification sites. Binding sites were defined by local structural comparisons of
      whole protein structures using the Protein Binding Sites (ProBiS) algorithm and
      transposition of ligands from the similar binding sites found to the query
      protein using the ProBiS-ligands approach with new improvements introduced in
      GenProBiS. Binding site surfaces were generated as three-dimensional grids
      encompassing the space occupied by predicted ligands. The server allows intuitive
      visual exploration of comprehensively mapped variants, such as human somatic mis
      sense mutations related to cancer and non-synonymous single nucleotide
      polymorphisms from 21 species, within the predicted binding sites regions for
      about 80 000 PDB protein structures using fast WebGL graphics. The GenProBiS web
      server is open and free to all users at http://genprobis.insilab.org.

PMID- 28498967
TI  - Surgical resection after neoadjuvant chemoradiation for oesophageal
      adenocarcinoma: what is the optimal timing?
AB  - OBJECTIVES: The purpose of this study was to determine the optimal timing of
      surgical resection of oesophageal adenocarcinoma following neoadjuvant
      chemoradiotherapy (nCRT). METHODS: nCRT before resection of oesophageal
      adenocarcinoma yields improved overall and progression-free survival. Despite the
      wide acceptance of tri-modal therapy, the optimal timing of surgical resection
      after nCRT is not well defined and existing studies are limited. Adults with
      Stage II/III oesophageal adenocarcinoma undergoing nCRT before surgery were
      identified from the National Cancer Database. Multivariable analysis using
      restricted cubic splines was used to identify an inflection point in clinical
      outcomes as a function of time between nCRT and surgery, dividing the cohort into
      short- and long-interval treatment groups, which were then compared. Adjusted
      rates of survival and margin status were compared between groups using
      multivariable analysis. RESULTS: Among 2444 patients, restricted cubic splines
      identified an inflection point at 56 days, dividing our cohort into 1533 short
      interval and 911 long-interval patients. Long-interval patients had a higher
      adjusted incidence of pathologic downstaging (odds ratio 1.38, confidence
      interval 1.02-1.85, P = 0.04) but no difference in margin positivity compared
      with short-interval patients (odds ratio 0.91, confidence interval 0.56-1.47, P =
      0.69). Worse overall survival was noted in the long-interval subgroup (hazard
      ratio 1.44, confidence interval 1.22-1.71, P < 0.001), but 30-day postoperative
      mortality was not statistically different (odds ratio 1.56, confidence interval
      0.9-2.72, P = 0.12). CONCLUSIONS: Restricted cubic splines provides an objective
      mechanism to more accurately delineate optimum timing between nCRT and surgical
      resection. A time interval of 56 days represents an interval where increased
      pathologic downstaging is balanced by decreased overall survival.

PMID- 28498968
TI  - The involvement of alcohol in hospital-treated self-harm and associated factors:
      findings from two national registries.
AB  - Background: Alcohol is often involved in hospital-treated self-harm. Therefore it
      is important to establish the role of alcohol in self-harm as well as to identify
      associated factors, in order to best inform service provision. Methods: Data on
      self-harm presentations to hospital emergency departments in Ireland and Northern
      Ireland from April 2012 to December 2013 were analysed. We calculated the
      prevalence of alcohol consumption in self-harm. Using Poisson regression models,
      we identified the factors associated with having consumed alcohol at the time of
      a self-harm act. Results: Alcohol was present in 43% of all self-harm acts, and
      more common in Northern Ireland (50 versus 37%). The factors associated with
      alcohol being involved were being male, aged between 25 and 64 years, and having
      engaged in a drug overdose or attempted drowning. Presentations made out-of-hours
      were more likely to have alcohol present and this was more pronounced for
      females. Patients with alcohol on board were also more likely to leave without
      having been seen by a clinician. Conclusions: This study has highlighted the
      prevalence of alcohol in self-harm presentations, and has identified factors
      associated with presentations involving alcohol. Appropriate out-of-hours
      services in emergency departments for self-harm presentations could reduce the
      proportion of presentations leaving without being seen by a clinician and
      facilitate improved outcomes for patients.

PMID- 28498969
TI  - DEVELOPMENT OF ISOTOPICALLY ENRICHED BORON-DOPED ALUMINA DOSIMETER FOR THERMAL
      NEUTRONS.
AB  - A novel optically stimulated luminescence (OSL) detector containing isotopically
      enriched boron was developed for thermal neutron dosimetry. Alumina containing
      isotopically enriched boron (Al2O3:B) was synthesised by the sol-gel method. The
      Al2O3:B was annealed up to ~1800 K. For X-ray diffractometer (XRD) analysis, the
      diffraction pattern of the Al2O3:B had reflex peaks corresponding to alpha-Al2O3.
      The sensitivity of Al2O3:B to photons was slightly 2% of that of a commercial
      Al2O3:C. The Al2O3:B detector had satisfactory linearity in X-ray dose
      measurement. A thermal neutron field was constructed using a 241Am-Be neutron
      source and graphite blocks. A pair of Al2O3:10B and Al2O3:11B detectors were set
      in the thermal neutron field. The response of Al2O3:10B was larger than that of
      Al2O3:11B owing to the 10B(n,alpha)7Li reactions. The sensitivity of Al2O3:10B to
      thermal neutrons was estimated to be two orders less than the photon sensitivity.
      Therefore, the pair of Al2O3:10B and Al2O3:11B detectors were useful for thermal
      neutron dosimetry.

PMID- 28498970
TI  - Results of a multimodal approach for the management of aortic coarctation and its
      complications in adults.
AB  - OBJECTIVES: We aimed to assess the results of various tailored management
      strategies for adults with coarctation in our centre. METHODS: We reviewed all
      adults patients treated for aortic caorctation between January 2000 and December
      2015 in our institution. The primary end point was a composite of death,
      perioperative stroke, paraplegia, need for unplanned reoperation or occurrence of
      pseudoaneurysm during the follow-up. The mean follow-up was 82 +/- 5 months.
      RESULTS: Sixty-three adults were treated for a native coarctation (n = 34), a
      recurrent coarctation (n = 14) or aneurysmal complication (n = 15). Mean age of
      the patients was 42 +/- 1.7 years. All but 1 patient with native coarctation
      (33/34, 97%) and recurrent coarctation (13/14, 93%) underwent endovascular repair
      and 10 (67%) patients with aneurysmal complications were treated surgically.
      Freedom from the primary composite end point was 94, 84 and 81% at 1, 5 and 10
      years, respectively, without difference between the 3 indication groups (P =
      0.96). CONCLUSIONS: A tailored management strategy is necessary to provide good
      results for the treatment of adults with aortic coarctation. Thus, centres that
      are involved in the care of this complex pathology should be able to propose a
      multimodal approach, either endovascular or surgical depending on patient's
      characteristics and anatomic features.

PMID- 28498972
TI  - Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte
      Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol
      Induced Developmental Toxicity.
AB  - With our recently developed in vitro physiologically based kinetic (PBK)
      modelling approach, we could extrapolate in vitro toxicity data to human toxicity
      values applying PBK-based reverse dosimetry. Ideally information on kinetic
      differences among human individuals within a population should be considered. In
      the present study, we demonstrated a modelling approach that integrated in vitro
      toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in
      interindividual human kinetic variation and derive chemical specific adjustment
      factors (CSAFs) for phenol-induced developmental toxicity. The present study
      revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of
      phenol in humans followed by UGT1A9. Monte Carlo simulations were performed
      taking into account interindividual variation in glucuronidation by these
      specific UGTs and in the oral absorption coefficient. Linking Monte Carlo
      simulations with PBK modelling, population variability in the maximum plasma
      concentration of phenol for the human population could be predicted. This
      approach provided a CSAF for interindividual variation of 2.0 which covers the
      99th percentile of the population, which is lower than the default safety factor
      of 3.16 for interindividual human kinetic differences. Dividing the dose-response
      curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF
      provided a dose-response curve that reflects the consequences of the
      interindividual variability in phenol kinetics for the developmental toxicity of
      phenol. The strength of the presented approach is that it provides insight in the
      effect of interindividual variation in kinetics for phenol-induced developmental
      toxicity, based on only in vitro and in silico testing.

PMID- 28498971
TI  - Deletion of RhoA in Progesterone Receptor-Expressing Cells Leads to Luteal
      Insufficiency and Infertility in Female Mice.
AB  - Ras homolog gene family, member A (RhoA) is widely expressed throughout the
      female reproductive system. To assess its role in progesterone receptor
      expressing cells, we generated RhoA conditional knockout mice RhoAd/d (RhoAf/f
      Pgr-Cre+/-). RhoAd/d female mice had comparable mating activity, serum
      luteinizing hormone, prolactin, and estradiol levels and ovulation with control
      but were infertile with progesterone insufficiency, indicating impaired
      steroidogenesis in RhoAd/d corpus luteum (CL). RhoA was highly expressed in wild
      type luteal cells and conditionally deleted in RhoAd/d CL. Gestation day 3.5
      (D3.5) RhoAd/d ovaries had reduced numbers of CL, less defined corpus luteal cord
      formation, and disorganized CL collagen IV staining. RhoAd/d CL had lipid droplet
      and free cholesterol accumulation, indicating the availability of cholesterol for
      steroidogenesis, but disorganized beta-actin and vimentin staining, indicating
      disrupted cytoskeleton integrity. Cytoskeleton is important for cytoplasmic
      cholesterol movement to mitochondria and for regulating mitochondria.
      Dramatically reduced expression of mitochondrial markers heat shock protein 60
      (HSP60), voltage-dependent anion channel, and StAR was detected in RhoAd/d CL.
      StAR carries out the rate-limiting step of steroidogenesis. StAR messenger RNA
      expression was reduced in RU486-treated D3.5 wild-type CL and tended to be
      induced in progesterone-treated D3.5 RhoAd/d CL, with parallel changes of HSP60
      expression. These data demonstrated the in vivo function of RhoA in CL luteal
      cell cytoskeleton integrity, cholesterol transport, StAR expression, and
      progesterone synthesis, and a positive feedback on StAR expression in CL by
      progesterone signaling. These findings provide insights into mechanisms of
      progesterone insufficiency.

PMID- 28498973
TI  - Chordoma Occurs in Young Children With Tuberous Sclerosis.
AB  - Chordomas are rare bony neoplasms usually unassociated with a familial tumor
      predisposition syndrome. The peak incidence of this midline axial skeletal tumor
      is in adulthood but when very young children are affected, consideration should
      be given to occurrence within the tuberous sclerosis (TS) complex, especially
      when presenting in neonates <3 months of age. To call attention to this
      association, we present a brachyury-immunopositive chordoma occurring in the
      skull base of a 2-month-old male infant who was later realized to have metastases
      to the subcutaneous tissues and lungs, as well as rhabdomyoma of the heart and
      renal cysts/angiomyolipomas, that is, characteristic features of the TS complex.
      We review the limited literature on this topic.

PMID- 28498974
TI  - Strong transcription blockage mediated by R-loop formation within a G-rich
      homopurine-homopyrimidine sequence localized in the vicinity of the promoter.
AB  - Guanine-rich (G-rich) homopurine-homopyrimidine nucleotide sequences can block
      transcription with an efficiency that depends upon their orientation, composition
      and length, as well as the presence of negative supercoiling or breaks in the non
      template DNA strand. We report that a G-rich sequence in the non-template strand
      reduces the yield of T7 RNA polymerase transcription by more than an order of
      magnitude when positioned close (9 bp) to the promoter, in comparison to that for
      a distal (~250 bp) location of the same sequence. This transcription blockage is
      much less pronounced for a C-rich sequence, and is not significant for an A-rich
      sequence. Remarkably, the blockage is not pronounced if transcription is
      performed in the presence of RNase H, which specifically digests the RNA strands
      within RNA-DNA hybrids. The blockage also becomes less pronounced upon reduced
      RNA polymerase concentration. Based upon these observations and those from
      control experiments, we conclude that the blockage is primarily due to the
      formation of stable RNA-DNA hybrids (R-loops), which inhibit successive rounds of
      transcription. Our results could be relevant to transcription dynamics in vivo
      (e.g. transcription 'bursting') and may also have practical implications for the
      design of expression vectors.

PMID- 28498976
TI  - Low back pain among taxi drivers: a cross-sectional study.
AB  - Background: Low back pain (LBP) is a common occupational problem for drivers all
      over the world. However, few epidemiological studies have investigated LBP among
      taxi drivers. Aims: To investigate the prevalence of LBP and associated work
      related factors among Chinese taxi drivers. Methods: A cross-sectional survey was
      administered to all participants. Using cluster sampling, questionnaires were
      collected from taxi drivers of three major taxi companies in Jinan, China.
      Univariate and multivariate logistic regressions were used to estimate the odd
      ratios (ORs) and 95% confidence intervals (CIs) among participants. Results: A
      total of 800 taxi drivers were invited to take part, with a participation rate of
      90%. The 1-year period prevalence of LBP was 54%. Multivariate logistic
      regression analysis revealed that longer daily driving duration (OR 3.3, 95% CI
      1.9-5.9), night shifts (OR 1.9, 95% CI 1.2-3.1) and increasing work years as a
      taxi driver (OR 1.7, 95% CI 1.2-2.5) were associated with increased risk of
      reporting LBP; while increased rest days per month (OR 0.8, 95% CI 0.7-0.9),
      longer sleep duration (OR 0.7, 95% CI 0.5-0.9) and more physical activity (OR
      0.5, 95% CI 0.3-0.8) were significantly associated with decreased risk of
      reporting LBP. Conclusions: The prevalence of LBP among professional taxi drivers
      in China was associated with a number of occupational features.

PMID- 28498978
TI  - Patient reported outcome of adult perioperative anaesthesia in the United
      Kingdom: a cross-sectional observational study.

PMID- 28498975
TI  - Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in
      axial spondyloarthritis: 4-year outcomes from RAPID-axSpA.
AB  - Objective: The aim was to assess the long-term safety and efficacy of
      certolizumab pegol over 4 years of continuous treatment in patients with axial
      spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA.
      Methods: RAPID-axSpA was a phase 3 randomized trial, double blind and placebo
      controlled to week 24, dose blind to week 48 and open label to week 204. Patients
      had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis
      international Society (ASAS) criteria, and had active disease. The assessed
      outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores,
      along with selected measures of remission. Further patient-reported outcomes,
      peripheral arthritis, enthesitis, uveitis and quality-of-life measures are also
      reported. Results: Two hundred and eighteen of 325 patients randomized (AS: 121;
      nr-axSpA: 97) received certolizumab pegol from week 0. Of these, 65% remained in
      the study at week 204 (AS: 67%; nr-axSpA: 63%). Across all outcomes, for AS and
      nr-axSpA, sustained improvements were observed to week 204 [week 204 overall
      axSpA: ASAS20: 54.1% (non-responder imputation); 83.7% (observed case, OC);
      ASAS40: 44.0% (non-responder imputation); 68.1% (OC); ASDAS inactive disease:
      32.1% (last observation carried forward); 31.4% (OC)]. In the safety set (n =
      315), there were 292.8 adverse events and 10.4 serious adverse events per 100
      patient-years. No deaths were reported. Conclusion: In the first study to
      evaluate the efficacy of an anti-TNF across both axSpA subpopulations,
      improvements in clinical and patient-reported outcomes at 24 and 96 weeks were
      sustained through 4 years of treatment, with no new safety signals. Trial
      registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01087762.

PMID- 28498979
TI  - Cohort Profile: The Tracking Opportunities and Problems Study (TOPP)-study of
      Norwegian children and their parents followed from infancy to early adulthood.

PMID- 28498977
TI  - Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions.
AB  - Mutations in MEGF10 cause early onset myopathy, areflexia, respiratory distress,
      and dysphagia (EMARDD), a rare congenital muscle disease, but the pathogenic
      mechanisms remain largely unknown. We demonstrate that short hairpin RNA (shRNA)
      mediated knockdown of Megf10, as well as overexpression of the pathogenic human
      p.C774R mutation, leads to impaired proliferation and migration of C2C12 cells.
      Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also
      show impaired proliferation and migration compared to myoblasts from wild type
      and mdx mice, whereas the dko mice show histological abnormalities that are not
      observed in either single mutant mouse. Cell proliferation and migration are
      known to be regulated by the Notch receptor, which plays an essential role in
      myogenesis. Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1
      interact via their respective intracellular domains. These interactions are
      impaired by the pathogenic p.C774R mutation. Megf10 regulation of myoblast
      function appears to be mediated at least in part via interactions with key
      components of the Notch signaling pathway, and defects in these interactions may
      contribute to the pathogenesis of EMARDD.

PMID- 28498980
TI  - Fowl adenovirus serotype 4: Epidemiology, pathogenesis, diagnostic detection, and
      vaccine strategies.
AB  - Fowl adenovirus (FAdV) serotype-4 is highly pathogenic for chickens, especially
      for broilers aged 3 to 5 wk, and it has emerged as one of the foremost causes of
      economic losses to the poultry industry in the last 30 years. The liver is a
      major target organ of FAdV-4 infections, and virus-infected chickens usually show
      symptoms of hydropericardium syndrome. The virus is very contagious, and it is
      spread both vertically and horizontally. It can be isolated from infected liver
      homogenates and detected by several laboratory diagnostic methods (including an
      agar gel immunodiffusion test, indirect immunofluorescence assays,
      counterimmunoelectrophoresis, enzyme-linked immunosorbent assays, restriction
      endonuclease analyses, polymerase chain reaction (PCR), real-time PCR, and high
      resolution melting-curve analyses). Although inactivated vaccines have been
      deployed widely to control the disease, attenuated live vaccines and subunit
      vaccines also have been developed, and they are more attractive vaccine
      candidates. This article provides a comprehensive review of FAdV-4, including its
      epidemiology, pathogenesis, diagnostic detection, and vaccine strategies.

PMID- 28498982
TI  - Using self-assessment to develop metacognition and self-regulated learners.
AB  - Student success is too often challenged by a lack of metacognition and ability to
      self-regulate learning. This commentary argues that the use of self-assessment to
      increase student metacognition positively impacts student learning and self
      regulation. In addition, several strategies for incorporating self-assessment
      will be presented.

PMID- 28498981
TI  - Splicing in immune cells-mechanistic insights and emerging topics.
AB  - Differential splicing of mRNAs not only enables regulation of gene expression
      levels, but also ensures a high degree of gene-product diversity. The extent to
      which splicing of mRNAs is utilized as a mechanism in immune cells has become
      evident within the last few years. Still, only a few of these mechanisms have
      been well studied. In this review, we discuss some of the best-understood
      mechanisms, for instance the differential splicing of CD45 in T cells, as well as
      immunoglobulin genes in B cells. Beyond that we provide general mechanistic
      insights on how, when and where this process takes place and discuss the current
      knowledge regarding these topics in immune cells. We also highlight some of the
      reported links to immune-related diseases, genome-wide sequencing studies that
      revealed thousands of differentially spliced transcripts, as well as splicing
      studies on immune cells that remain mechanistically not fully understood. We
      thereby display potential emerging topics for future studies centered on splicing
      mechanisms in immune cells.

PMID- 28498983
TI  - Atypical hand, foot and mouth disease due to Coxsackievirus A6 in a traveler
      returning from Indonesia to Italy.

PMID- 28498984
TI  - Inheritance of vernalization memory at FLOWERING LOCUS C during plant
      regeneration.
AB  - Specific gene states can be transmitted to subsequent cell generations through
      mitosis involving particular chromatin (epigenetic) states. During reproduction
      of plants and animals, however, most epigenetic states are reset to allow
      development to start anew. Flowering is one of the critical developmental steps
      by which plants acquire their reproductive capacity. This phase transition is
      controlled by environmental signals and autonomous regulation. The FLOWERING
      LOCUS C (FLC) gene is a flowering repressor that is epigenetically silenced after
      long-term exposure to cold, ensuring flowering in the spring season. In
      Arabidopsis thaliana, epigenetically silenced FLC expression is reset during
      sexual reproduction. Plants have a remarkable potential to regenerate from
      somatic cells. However, little is known about whether the regeneration process is
      similar to sexual reproduction in terms of affecting chromatin states. Here, we
      tested whether FLC silencing is reset during in vitro regeneration.
      Transcriptional repression and high H3K27me3 at FLC were both stably transmitted,
      resulting in early flowering in regenerated shoots. Thus, the silenced epigenetic
      state of FLC is reset only during sexual reproduction and not during in vitro
      regeneration. In contrast, the active epigenetic state of FLC was only partially
      maintained through in vitro reproduction, suggesting that regeneration causes
      stochastic FLC silencing.

PMID- 28498985
TI  - HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral
      Replication.
AB  - Background: Human immunodeficiency virus (HIV) antibodies are generated and
      maintained by ongoing systemic expression of HIV antigen. We investigated whether
      HIV antibody responses as measured by high-throughput quantitative and
      qualitative assays could be used to indirectly measure persistent HIV replication
      in individuals receiving antiretroviral therapy (ART). Methods: HIV antibody
      responses were measured over time in the presence or absence of suppressive ART
      and were compared to the HIV reservoir size and expression of antiviral
      restriction factors. Results: Among untreated individuals, including both elite
      controllers (ie, persons with a viral load of <=40 copies/mL) and noncontrollers,
      antibody parameters were stable over time and correlated with the individual
      viral load. Viral suppression with ART led to a progressive decline in antibody
      responses after treatment induction that persisted for 5-7 years. Higher levels
      of HIV antibodies during suppressive therapy were associated with later
      initiation of ART after infection, with higher DNA and cell-associated RNA
      levels, and with lower expression of multiple anti-HIV host restriction factors.
      Discussion: These findings suggest that declining antibody levels during ART
      reflect lower levels of antigen production and/or viral replication in the
      persistent HIV reservoir. Results of relatively inexpensive and quantitative HIV
      antibody assays may be useful indirect markers that enable efficient monitoring
      of the viral reservoir and suppression during functional-cure interventions.

PMID- 28498986
TI  - Sequence of inoculation influences the nature of extracellular polymeric
      substances and biofilm formation in Azotobacter chroococcum and Trichoderma
      viride.
AB  - Extracellular polymeric substances (EPS) are important structural components of
      biofilms. In the present study, the EPS in biofilms developed using two
      agriculturally beneficial organisms-Azotobacter chroococcum (Az) and Trichoderma
      viride (Tv) were quantified and characterised. Time course experiments were
      undertaken to optimise the EPS yield of biofilm samples resulting from coculture
      and staggered inoculation. The EPS produced during biofilm formation was found to
      differ quantitatively and qualitatively in individual cultures (Az alone, Tv
      alone), and in treatments differing in the sequence of inoculation of bacterium
      and fungus (Az + Tv coculture, staggered inoculation of Az followed by Tv i.e. Az
      - Tv, or Tv followed by Az i.e. Tv - Az). Significant enhancement in terms of
      growth and biofilm formation, as compared to individual inoculation was recorded,
      with Tv - Az exhibiting higher values of these attributes. The EPS from biofilms
      showed significantly higher concentrations of protein, acetyl, and uronic acids,
      while planktonic EPS recorded higher total carbohydrates. Fourier transform
      infrared spectroscopy analyses illustrated the significant influence on chemical
      and structural aspects of EPS (planktonic and biofilm). This represents a first
      report correlating EPS production, cell aggregation and biofilm formation during
      bacterial-fungal biofilm development, which can have implications in the
      colonisation of soil and plants.

PMID- 28498987
TI  - Genetic Structure and Phylogeography of the Leopard Cat (Prionailurus
      bengalensis) Inferred from Mitochondrial Genomes.
AB  - The Leopard cat Prionailurus bengalensis is a habitat generalist that is widely
      distributed across Southeast Asia. Based on morphological traits, this species
      has been subdivided into 12 subspecies. Thus far, there have been few molecular
      studies investigating intraspecific variation, and those had been limited in
      geographic scope. For this reason, we aimed to study the genetic structure and
      evolutionary history of this species across its very large distribution range in
      Asia. We employed both PCR-based (short mtDNA fragments, 94 samples) and high
      throughput sequencing based methods (whole mitochondrial genomes, 52 samples) on
      archival, noninvasively collected and fresh samples to investigate the
      distribution of intraspecific genetic variation. Our comprehensive sampling
      coupled with the improved resolution of a mitochondrial genome analyses provided
      strong support for a deep split between Mainland and Sundaic Leopard cats.
      Although we identified multiple haplogroups within the species' distribution, we
      found no matrilineal evidence for the distinction of 12 subspecies. In the
      context of Leopard cat biogeography, we cautiously recommend a revision of the
      Prionailurus bengalensis subspecific taxonomy: namely, a reduction to 4
      subspecies (2 mainland and 2 Sundaic forms).

PMID- 28498988
TI  - Complementary Roles of Phenotype and Genotype in Subspecies Delimitation.

PMID- 28498989
TI  - Determination of the Genetic Architecture Underlying Short Wavelength Sensitivity
      in Lake Malawi Cichlids.
AB  - African cichlids are an exemplary system to study organismal diversity and rapid
      speciation. Species differ in external morphology including jaw shape and body
      coloration, but also differ in sensory systems including vision. All cichlids
      have 7 cone opsin genes with species differing broadly in which opsins are
      expressed. The differential opsin expression results in closely related species
      with substantial differences in spectral sensitivity of their photoreceptors. In
      this work, we take a first step in determining the genetic basis of opsin
      expression in cichlids. Using a second generation cross between 2 species with
      different opsin expression patterns, we make a conservative estimate that short
      wavelength opsin expression is regulated by a few loci. Genetic mapping in 96 F2
      hybrids provides clear evidence of a cis-regulatory region for SWS1 opsin that
      explains 34% of the variation in expression between the 2 species. Additionally,
      in situ hybridization has shown that SWS1 and SWS2B opsins are coexpressed in
      individual single cones in the retinas of F2 progeny. Results from this work will
      contribute to a better understanding of the genetic architecture underlying opsin
      expression. This knowledge will help answer long-standing questions about the
      evolutionary processes fundamental to opsin expression variation and how this
      contributes to adaptive cichlid divergence.

PMID- 28498990
TI  - Genetic Kinship Analyses Reveal That Gray's Beaked Whales Strand in Unrelated
      Groups.
AB  - Some marine mammals are so rarely seen that their life history and social
      structure remain a mystery. Around New Zealand, Gray's beaked whales (Mesoplodon
      grayi) are almost never seen alive, yet they are a commonly stranded species.
      Gray's are unique among the beaked whales in that they frequently strand in
      groups, providing an opportunity to investigate their social organization. We
      examined group composition and genetic kinship in 113 Gray's beaked whales with
      samples collected over a 20-year period. Fifty-six individuals stranded in 19
      groups (2 or more individuals), and 57 whales stranded individually.
      Mitochondrial control region haplotypes and microsatellite genotypes (16 loci)
      were obtained for 103 whales. We estimated pairwise relatedness between all pairs
      of individuals and average relatedness within, and between, groups. We identified
      6 mother-calf pairs and 2 half-siblings, including 2 whales in different
      strandings 17 years and 1500 km apart. Surprisingly, none of the adults stranding
      together were related suggesting that groups are not formed through the retention
      of kin. These data suggest that both sexes may disperse from their mothers, and
      groups consisting of unrelated subadults are common. We also found no instances
      of paternity within the groups. Our results provide the first insights into
      dispersal, social organization, and the mating system in this rarely sighted
      species. Why whales strand is still unknown but, in Gray's beaked whales, the
      dead can tell us much about the living.

PMID- 28498991
TI  - Population Differentiation in Common Walnut (Juglans regia L.) across Major Parts
      of Its Native Range-Insights from Molecular and Morphometric Data.
AB  - Juglans regia is an economically highly important species for fruit and wood
      production in the warm temperate and subtropical zones of the Northern
      Hemisphere. Besides the natural influence of climatic and geomorphological
      barriers, its genetic structure has been strongly modified by humans and the
      population history is still unclear. For this reason, we investigated mainly
      natural walnut populations across the Eurasian continent on a molecular (44
      populations, 581 trees) and morphometric level (23 populations, 1391 ripe nuts).
      Population genetic diversity and differentiation were examined by using 7
      microsatellite loci. Morphometric characteristics of the nuts (mainly roundness
      index and nut density) were used to estimate trait variation and population
      differentiation. Highest allelic richness Rs12 = 7.05 was observed in a Pakistani
      and the lowest value Rs12 = 3.04 in a Kyrgyz population. The genetic
      differentiation among populations was high (FST = 0.217; RST = 0.530) indicating
      a strong phylogeographic pattern. While variation of the roundness index within
      single populations was high, this trait neither differentiated geographical
      regions nor was it associated to genetic clusters. Approximated QST based on this
      trait equalled FST, while approximated QST based on nut density considerably
      exceeded FST, indicating selection. Nut density was moderately correlated with
      altitude, latitude, and longitude, and differentiated populations according to
      their origin. Pakistani and Indian populations showed highest nut densities.
      These South Asian populations contain putatively ancestral nut forms, which
      probably have been lost in other populations as a consequence of human selection.

PMID- 28498992
TI  - Reproductive Strategy of the Polyploid Species Varronia curassavica Jacq. in
      Restinga Environment.
AB  - This study aimed to elucidate the breeding strategies of Varronia curassavica, an
      important medicinal species associated with Brazilian restinga. This was
      accomplished by combining phenological and genetic data. Every 2 weeks over a
      period of 2 years, we measured flowering and fruiting phenology to evaluate the
      activity and intensity of phenophases (n = 60). We evaluated the mating system,
      pollen ovule ratio and genotypes from progeny and mother plants using 8 nuclear
      microsatellite loci. We observed flowering and fruiting of V. curassavica at low
      intensity throughout the entire year, but with 2 distinct peaks, one of which was
      seasonal, corresponding to the period of gradual increase of temperature and
      photoperiod. Overlapping of flowering and fruiting strategies favors gene flow
      among different groups of individuals and between populations by attraction of
      fauna throughout the year. Analysis of the mating system indicates that V.
      curassavica is a typical outcrossed species (t^ = 0.98; pollen/ovule ratio =
      7087.50). Combining phenology with genetic studies improved our understanding of
      the reproductive strategies of this species. The typical outcrossing system of V.
      curassavica reflects the existence of functional self-incompatibility mechanisms
      still unaffected by changes in genetic balance by polyploidy.

PMID- 28498993
TI  - DEOGEN2: prediction and interactive visualization of single amino acid variant
      deleteriousness in human proteins.
AB  - High-throughput sequencing methods are generating enormous amounts of genomic
      data, giving unprecedented insights into human genetic variation and its relation
      to disease. An individual human genome contains millions of Single Nucleotide
      Variants: to discriminate the deleterious from the benign ones, a variety of
      methods have been developed that predict whether a protein-coding variant likely
      affects the carrier individual's health. We present such a method, DEOGEN2, which
      incorporates heterogeneous information about the molecular effects of the
      variants, the domains involved, the relevance of the gene and the interactions in
      which it participates. This extensive contextual information is non-linearly
      mapped into one single deleteriousness score for each variant. Since for the non
      expert user it is sometimes still difficult to assess what this score means, how
      it relates to the encoded protein, and where it originates from, we developed an
      interactive online framework (http://deogen2.mutaframe.com/) to better present
      the DEOGEN2 deleteriousness predictions of all possible variants in all human
      proteins. The prediction is visualized so both expert and non-expert users can
      gain insights into the meaning, protein context and origins of each prediction.

PMID- 28498994
TI  - ThreaDomEx: a unified platform for predicting continuous and discontinuous
      protein domains by multiple-threading and segment assembly.
AB  - We develop a hierarchical pipeline, ThreaDomEx, for both continuous domain (CD)
      and discontinuous domain (DCD) structure predictions. Starting from a query
      sequence, ThreaDomEx first threads it through the PDB to identify multiple
      structure templates, where a profile of domain conservation score (DC-score) is
      derived for domain-segment assignment. To further detect DCDs that consist of
      separated segments along the sequence, a boundary-clustering algorithm is used to
      refine the DCD-linker locations. In case that the templates do not contain DCDs,
      a domain-segment assembly process, guided by symmetry comparison, is applied for
      further DCD detections. ThreaDomEx was tested a set of 1111 proteins and achieved
      a normalized domain overlap score of 89.3% compared to experimental data, which
      is significantly higher than other state-of-the-art methods. It also recalls
      26.7% of DCDs with 72.7% precision on the proteins for which threading failed to
      detect any DCDs. The server provides facilities for users to interactively refine
      the domain models by adjusting DC-score threshold, deleting and adding domain
      linkers, and assembling domain segments, which are particularly helpful for the
      hard targets for which current methods have a low accuracy while human-expert
      knowledge and experimental insights can be used for refining models. ThreaDomEX
      server is available at http://zhanglab.ccmb.med.umich.edu/ThreaDomEx.

PMID- 28498995
TI  - Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone:
      Clinical, Virological, Immunological, and Evolutionary Analyses.
AB  - We performed Ebola virus disease diagnosis and viral load estimation for Ebola
      cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January
      March 2015) and analyzed antibody and cytokine levels and the viral genome
      sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with
      an overall case fatality rate of 46.8%. Fatal cases exhibited significantly
      higher levels of viral loads, cytokines, and chemokines at late stages of
      infection versus early stage compared with survivors. The viruses converged in a
      new clade within sublineage 3.2.4, which had a significantly lower case fatality
      rate.

PMID- 28498996
TI  - Protective Factors in the Intestinal Microbiome Against Clostridium difficile
      Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - Background: Clostridium difficile infection (CDI) is a frequent complication in
      recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who
      receive intensive treatments that significantly disrupt the intestinal
      microbiota. In this study, we examined the microbiota composition of allo-HSCT
      recipients to identify bacterial colonizers that confer protection against CDI
      after engraftment. Methods: Feces collected from adult recipients allo-HSCT at
      engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed
      from each sample. Bacterial taxa with protective effects against development of
      CDI were identified by means of linear discriminant analysis effect size analysis
      and then further assessed with clinical predictors of CDI using survival
      analysis. Results: A total of 234 allo-HSCT recipients were studied;
      postengraftment CDI developed in 53 (22.6%). Within the composition of the
      microbiota, the presence of 3 distinct bacterial taxa was correlated with
      protection against CDI: Bacteroidetes, Lachnospiraceae, and Ruminococcaceae.
      Colonization with these groups at engraftment was associated with a 60% lower
      risk of CDI, independent of clinical factors. Conclusions: Colonization with
      these 3 bacterial groups is associated with a lower risk of CDI. These groups
      have been shown to be vital components of the intestinal microbiota. Targeted
      efforts to maintain them may help minimize the risk of CDI in this at-risk
      population.

PMID- 28498997
TI  - Initiation of gametocytogenesis at very low parasite density in Plasmodium
      falciparum infection.
AB  - The recent focus on the elimination of malaria has led to an increased interest
      in the role of sexual stages in its transmission. We introduce Plasmodium
      falciparum gametocyte exported protein-5 (PfGEXP5) transcript analysis as an
      important tool for evaluating the earliest (ring) stage sexual gametocytes in the
      blood of infected individuals. We show that gametocyte rings are detected in the
      peripheral blood immediately following establishment of asexual infections
      without the need for triggers such as high-density asexual parasitemia or drug
      treatment. Committed gametocytes are refractory to the commonly used drug
      piperaquine, and mature gametocytes reappear in the bloodstream 10 days after the
      initial appearance of gametocyte rings. A further wave of commitment is observed
      following recrudescent asexual parasitemia, and these gametocytes are again
      refractory to piperaquine treatment. This work has implications for monitoring
      gametocyte and transmission dynamics and responses to drug treatment.

PMID- 28498998
TI  - Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces:
      Mucus Protects Virions From Acid and Digestive Juices.
AB  - Although viral RNA or infectious virions have been detected in the feces of
      individuals infected with human influenza A and B viruses (IAV/IBV), the
      mechanism of viral survival in the gastrointestinal tract remains unclear. We
      developed a model that attempts to recapitulate the conditions encountered by a
      swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices
      (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA
      and virions, allowing the virus to retain its infectivity. Our results suggest
      that virions and RNA present in swallowed mucus are not inactivated or degraded
      by the gastrointestinal environment, allowing their detection in feces.

PMID- 28498999
TI  - The Effect of Religion and Spirituality on Cognitive Function: A Systematic
      Review.
AB  - Purpose of the Study: The maintenance of cognitive health is an important
      component of healthy aging. Abnormal cognitive decline can signal the onset of
      dementing disorders such as Alzheimer's disease (AD). Normal cognitive decline
      can also adversely affect the health of aging populations. We investigated the
      association between religious/spiritual involvement (R/SI) and cognitive function
      in adults of any age and any setting. We also examined whether social engagement
      acts as a mediator or moderator of the effect of R/SI on cognitive function, and
      whether the association between R/SI and cognitive function differs according to
      how each of these constructs is measured. Design and Methods: We conducted a
      systematic review of articles published between 1990 and September 2016 by
      searching OVID MEDLINE, PSYCHINFO, EMBASE, and Google Advanced Search. We
      included studies with a comparison group (cohort, case-control, cross-sectional)
      that reported on R/SI (exposure) and cognitive function (outcome). Results: Of
      the 6,300 citations obtained in the literature search, 17 met our eligibility
      criteria and were included in the review. Most of the included studies (82%)
      reported positive associations between R/SI and cognitive function. R/SI appears
      to be protective against cognitive decline in middle- and old-age adults.
      Implications: Public health practitioners should not overlook the benefits of
      enabling religious/spiritual practices among religious adults (i.e., offering
      ride programs could help isolated elders attend religious gatherings).

PMID- 28499000
TI  - 238U CONTENT IN URINE OF URANIUM MINERS AND ITS MODELED VALUES.
AB  - The aim of the study is to make a comparison of daily 238U excretion in urine
      among 115 active uranium miners and its modeled values obtained from inhalation
      intake of long-lived alpha emitters as measured by personal dosemeters and
      assessed by biokinetic models for different absorption parameters settings for
      inhaled uranium. A total of 144 spot samples of urine were collected. The 238U
      content was measured using high-resolution inductively coupled plasma mass
      spectrometry method. To obtain estimates of the daily excreted values, the daily
      values were calculated according to the expected daily excretion of creatinine
      assessed individually for each miner. When determining the relation between the
      experimentally found data and the modeled data, a high emphasis was placed on
      uncertainty of the both compared quantities. All the tested absorption parameters
      settings produced in average 1.4-4.7-fold higher values than the experimentally
      found values in the urine.

PMID- 28499002
TI  - Moving Rehabilitation Research Forward at NIH.

PMID- 28499001
TI  - Is Pelvic-Floor Muscle Training a Physical Therapy or a Behavioral Therapy? A
      Call to Name and Report the Physical, Cognitive, and Behavioral Elements.
AB  - This perspective article explores whether pelvic-floor muscle training (PFMT) for
      the management of female urinary incontinence and prolapse is a physical therapy
      or a behavioral therapy. The primary aim is to demonstrate that it is both. A
      secondary aim is to show that the plethora of terms used for PFMT is potentially
      confusing and that current terminology inadequately represents the full intent,
      content, and delivery of this complex intervention. While physical therapists may
      be familiar with exercise terms, the details are often incompletely reported;
      furthermore, physical therapists are less familiar with the terminology used in
      accurately representing cognitive and behavioral therapy interventions, which
      results in these elements being even less well reported. Thus, an additional aim
      is to provide greater clarity in the terminology used in the reporting of PFMT
      interventions, specifically, descriptions of the exercise and behavioral
      elements. First, PFMT is described as a physical therapy and as an exercise
      therapy informed predominantly by the discipline of physical therapy. However,
      effective implementation requires use of the cognitive and behavioral
      perspectives of the discipline of psychology. Second, the theoretical
      underpinning of the psychology-informed elements of PFMT is summarized. Third, to
      address some identified limitations and confusion in current terminology and
      reporting, recommendations for ways in which physical therapists can incorporate
      the psychology-informed elements of PFMT alongside the more familiar exercise
      therapy-informed elements are made. Fourth, an example of how both elements can
      be described and reported in a PFMT intervention is provided. In summary, this
      perspective explores the underlying concepts of PFMT to demonstrate that it is
      both a physical intervention and a behavioral intervention and that it can and
      should be described as such, and an example of the integration of these elements
      into clinical practice is provided.

PMID- 28499004
TI  - Rehabilitation Research at the National Institutes of Health:: Moving the Field
      Forward (Executive Summary).
AB  - Approximately 53 million Americans live with a disability. For decades, the
      National Institutes of Health (NIH) has been conducting and supporting research
      to discover new ways to minimize disability and enhance the quality of life of
      people with disabilities. After the passage of the American With Disabilities
      Act, the NIH established the National Center for Medical Rehabilitation Research
      with the goal of developing and implementing a rehabilitation research agenda.
      Currently, a total of 17 institutes and centers at NIH invest more than $500
      million per year in rehabilitation research. Recently, the director of NIH, Dr
      Francis Collins, appointed a Blue Ribbon Panel to evaluate the status of
      rehabilitation research across institutes and centers. As a follow-up to the work
      of that panel, NIH recently organized a conference under the title
      "Rehabilitation Research at NIH: Moving the Field Forward." This report is a
      summary of the discussions and proposals that will help guide rehabilitation
      research at NIH in the near future.This article is being published almost
      simultaneously in the following six journals: American Journal of Occupational
      Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of
      Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair,
      Physical Therapy, and Rehabilitation Psychology. Citation information is as
      follows: Frontera WR, Bean JF, Damiano D, et al. Am J Phys Med Rehabil.
      2017;97(4):393-403.

PMID- 28499003
TI  - National Institutes of Health Research Plan on Rehabilitation: NIH Medical
      Rehabilitation Coordinating Committee.
AB  - One in five Americans experiences disability that affects their daily function
      because of impairments in mobility, cognitive function, sensory impairment, or
      communication impairment. The need for rehabilitation strategies to optimize
      function and reduce disability is a clear priority for research to address this
      public health challenge. The National Institutes of Health (NIH) recently
      published a Research Plan on Rehabilitation that provides a set of priorities to
      guide the field over the next 5 years. The plan was developed with input from
      multiple Institutes and Centers within the NIH, the National Advisory Board for
      Medical Rehabilitation Research, and the public. This article provides an
      overview of the need for this research plan, an outline of its development, and a
      listing of six priority areas for research. The NIH is committed to working with
      all stakeholder communities engaged in rehabilitation research to track progress
      made on these priorities and to work to advance the science of medical
      rehabilitation.This article is being published almost simultaneously in the
      following six journals: American Journal of Occupational Therapy, American
      Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine
      and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and
      Rehabilitation Psychology. Citation information is as follows: NIH Medical
      Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407.

PMID- 28499005
TI  - Rehabilitation for Women and Men With Pelvic-Floor Dysfunction.

PMID- 28499006
TI  - Clinical characteristics and change in the antibody titres of patients with anti
      MDA5 antibody-positive inflammatory myositis.
AB  - Objective: The aim of this study was to evaluate the clinical characteristics of
      patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody
      positive inflammatory myositis, and the change in anti-MDA5 antibody titres
      before and after onset. Method: For 105 PM/DM patients, newly diagnosed in our
      hospital within the period 2008-2016, serum anti-MDA5 antibody levels were
      measured at diagnosis and after treatment by ELISA using the MESACUP anti-MDA5
      test. The relationships between anti-MDA5 antibody levels and clinical
      manifestations, laboratory data, and mortality were examined. Result: Compared
      with patients who were anti-MDA5 antibody negative, those who were antibody
      positive demonstrated more frequent dermatitis, clinically amyopathic DM,
      interstitial lung disease and rapid-progressive interstitial lung disease, as
      well as significantly higher serum ferritin, significantly lower creatine kinase
      and aldolase, and significantly less frequent ANA (?1:160) and anti-cytoplasmic
      pattern of ANA staining positivity. Anti-MDA5 antibody titres were examined
      before disease onset in two patients; one showed antibody positivity with low
      titres 2 years earlier, while both exhibited increased titres at onset. Anti-MDA5
      antibody titres declined significantly less in survivors than in non-survivors
      after treatment; however, there was no significant difference between the two
      groups when the rate was compared at 2 months after treatment. Conclusion: An
      initial decrease in anti-MDA5 antibody titre after commencement of treatment was
      observed in most of the patients, including in fatal cases, suggesting that this
      may not necessarily be a useful marker for treatment of patients with DM.

PMID- 28499007
TI  - Shifts in microbial trophic strategy explain different temperature sensitivity of
      CO2 flux under constant and diurnally varying temperature regimes.
AB  - Understanding soil CO2 flux temperature sensitivity (Q10) is critical for
      predicting ecosystem-level responses to climate change. Yet, the effects of
      warming on microbial CO2 respiration still remain poorly understood under current
      Earth system models, partly as a result of thermal acclimation of organic matter
      decomposition. We conducted a 117-day incubation experiment under constant and
      diurnally varying temperature treatments based on four forest soils varying in
      vegetation stand and soil horizon. Our results showed that Q10 was greater under
      varying than constant temperature regimes. This distinction was most likely
      attributed to differences in the depletion of available carbon between constant
      high and varying high-temperature treatments, resulting in significantly higher
      rates of heterotrophic respiration in the varying high-temperature regime. Based
      on 16S rRNA gene sequencing data using Illumina, the varying high-temperature
      regime harbored higher prokaryotic alpha-diversity, was more dominated by the
      copiotrophic strategists and sustained a distinct community composition, in
      comparison to the constant-high treatment. We found a tightly coupled
      relationship between Q10 and microbial trophic guilds: the copiotrophic
      prokaryotes responded positively with high Q10 values, while the oligotrophs
      showed a negative response. Effects of vegetation stand and soil horizon
      consistently supported that the copiotrophic vs oligotrophic strategists
      determine the thermal sensitivity of CO2 flux. Our observations suggest that
      incorporating prokaryotic functional traits, such as shifts between copiotrophy
      and oligotrophy, is fundamental to our understanding of thermal acclimation of
      microbially mediated soil organic carbon cycling. Inclusion of microbial
      functional shifts may provide the potential to improve our projections of
      responses in microbial community and CO2 efflux to a changing environment in
      forest ecosystems.

PMID- 28499008
TI  - RiPPMiner: a bioinformatics resource for deciphering chemical structures of RiPPs
      based on prediction of cleavage and cross-links.
AB  - Ribosomally synthesized and post-translationally modified peptides (RiPPs)
      constitute a rapidly growing class of natural products with diverse structures
      and bioactivities. We have developed RiPPMiner, a novel bioinformatics resource
      for deciphering chemical structures of RiPPs by genome mining. RiPPMiner derives
      its predictive power from machine learning based classifiers, trained using a
      well curated database of more than 500 experimentally characterized RiPPs.
      RiPPMiner uses Support Vector Machine to distinguish RiPP precursors from other
      small proteins and classify the precursors into 12 sub-classes of RiPPs. For
      classes like lanthipeptide, cyanobactin, lasso peptide and thiopeptide, RiPPMiner
      can predict leader cleavage site and complex cross-links between post
      translationally modified residues starting from genome sequences. RiPPMiner can
      identify correct cross-link pattern in a core peptide from among a very large
      number of combinatorial possibilities. Benchmarking of prediction accuracy of
      RiPPMiner on a large lanthipeptide dataset indicated high sensitivity,
      specificity, accuracy and precision. RiPPMiner also provides interfaces for
      visualization of the chemical structure, downloading of simplified molecular
      input line-entry system and searching for RiPPs having similar sequences or
      chemical structures. The backend database of RiPPMiner provides information about
      modification system, precursor sequence, leader and core sequence, modified
      residues, cross-links and gene cluster for more than 500 experimentally
      characterized RiPPs. RiPPMiner is available at
      http://www.nii.ac.in/rippminer.html.

PMID- 28499010
TI  - Acute eosinophilic pneumonia following artenimol-piperaquine exposure.
AB  - Acute eosinophilic pneumonia (AEP) has been reported following chloroquine or
      mefloquine exposure, both structurally related to piperaquine. We report a case
      of AEP with typical CT scan patterns, hypereosinophilia in blood (9.8 109/l), and
      bronchoalveolar lavage (78% of 600 000 cells/ml), 10 days after artenimol
      piperaquine exposure in a 26-year-old man.

PMID- 28499009
TI  - A viral suppressor of RNA silencing inhibits ARGONAUTE 1 function by precluding
      target RNA binding to pre-assembled RISC.
AB  - In most eukaryotes, RNA silencing is an adaptive immune system regulating key
      biological processes including antiviral defense. To evade this response, viruses
      of plants, worms and insects have evolved viral suppressors of RNA silencing
      proteins (VSRs). Various VSRs, such as P1 from Sweet potato mild mottle virus
      (SPMMV), inhibit the activity of RNA-induced silencing complexes (RISCs)
      including an ARGONAUTE (AGO) protein loaded with a small RNA. However, the
      specific mechanisms explaining this class of inhibition are unknown. Here, we
      show that SPMMV P1 interacts with AGO1 and AGO2 from Arabidopsis thaliana, but
      solely interferes with AGO1 function. Moreover, a mutational analysis of a newly
      identified zinc finger domain in P1 revealed that this domain could represent an
      effector domain as it is required for P1 suppressor activity but not for AGO1
      binding. Finally, a comparative analysis of the target RNA binding capacity of
      AGO1 in the presence of wild-type or suppressor-defective P1 forms revealed that
      P1 blocks target RNA binding to AGO1. Our results describe the negative
      regulation of RISC, the small RNA containing molecular machine.

PMID- 28499011
TI  - Fatal case of chikungunya and concomitant thrombotic thrombocytopenic purpura in
      French Guiana during air flight medical evacuation.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy
      associated to severe ADAMTS13 deficiency. It has been linked to various viral
      infections. Among arboviruses, only Crimean-Congo haemorrhagic fever and dengue
      fever have been linked to this severe disease. We report the first documented
      case of TTP concomitant to Chikungunya virus infection.

PMID- 28499012
TI  - Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive
      Resilience in the Nun and Honolulu-Asia Aging Studies.
AB  - Two population-based studies key to advancing knowledge of brain aging are the
      Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their
      neuropathologic data allows cross comparison, with findings common to both
      studies likely generalizable, while distinct observations may point to aging
      brain changes that are dependent on sex, ethnicity, environment, or lifestyle
      factors. Here, we expanded the neuropathologic evaluation of these 2 studies
      using revised NIA-Alzheimer's Association guidelines and compared directly the
      neuropathologic features of resistance and apparent cognitive resilience. There
      were significant differences in prevalence of Alzheimer disease neuropathologic
      change, small vessel vascular brain injury, and Lewy body disease between these 2
      studies, suggesting that sex, ethnicity, and lifestyle factors may significantly
      influence resistance to developing brain injury with age. In contrast,
      hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive
      performance, suggesting that hippocampal sclerosis could act sequentially with
      other diseases to impair cognitive function. Strikingly, despite these observed
      differences, the proportion of individuals resistant to all 4 diseases of brain
      or displaying apparent cognitive resilience was virtually identical between HAAS
      and Nun Study participants. Future in vivo validation of these results awaits
      comprehensive biomarkers of these 4 brain diseases.

PMID- 28499014
TI  - Captive Ancestry Upwardly Biases Estimates of Relative Reproductive Success.
AB  - Supplementation programs, which release captive-born individuals into the wild,
      are commonly used to demographically bolster declining populations. In order to
      evaluate the effectiveness of these programs, the reproductive success of captive
      born individuals released into the wild is often compared to the reproductive
      success of wild-born individuals in the recipient population (relative
      reproductive success, RRS). However, if there are heritable reductions in fitness
      associated with captive breeding, gene flow from captive-born individuals into
      the wild population can reduce the fitness of the wild population. Here, we show
      that when captive ancestry in the wild population reduces mean population
      fitness, estimates of RRS are upwardly biased, meaning that the relative fitness
      of captive-born individuals is over-estimated. Furthermore, the magnitude of this
      bias increases with the length of time that a supplementation program has been
      releasing captive-born individuals. This phenomenon has long-term conservation
      impacts since management decisions regarding the design of a supplementation
      program and the number of individuals to release can be based, at least in part,
      on RRS estimates. Therefore, we urge caution in the interpretation of relative
      fitness measures when the captive ancestry of the wild population cannot be
      precisely measured.

PMID- 28499013
TI  - GANTRY ANGULATION EFFECTS ON CT DOSE ALONG THE Z-AXIS DIRECTION IN HEAD
      EXAMINATIONS.
AB  - The purpose of this study was to evaluate the effects of the gantry angulation on
      dose profiles along the z-axis, the CTDIW value and the CTDIW efficiency in the
      head examinations. A Monte Carlo simulation model of a GE LightSpeed 16-slice CT
      scanner was developed by a GATE toolkit. The CTDI100 in air at the isocenter and
      in a head dosimetry phantom were measured using a pencil ion chamber. Dose
      profiles were studied in the central and peripheral holes of the head phantom
      using thermoluminescence LiF disc dosemeters for gantry angulations of 0 degrees
      , 10 degrees  and 20 degrees . Results show a small shift for only the peripheral
      dose profiles with increasing the gantry angulation (maximum shift of 24 mm at 20
      degrees ). The peak amplitude of the dose profiles was reduced for both of the
      central and peripheral holes by ~5%, while the CTDIW values and the CTDIW
      efficiencies did not change significantly.

PMID- 28499015
TI  - MRI 'EXPOSIMETRY': HOW TO ANALYZE, COMPARE AND REPRESENT WORKER EXPOSURE TO
      STATIC MAGNETIC FIELD?
AB  - Worker exposure to electromagnetic fields (EMF) is a growing concern of
      international commissions. A European directive from 2013 (2013/35/EU) recommend
      to estimate or measure EMF exposure of all exposed workers. Magnetic resonance
      imaging (MRI) workers are specially concerned by this point because they work all
      day long in the vicinity of a very strong magnet (generally 1.5 or 3 T), which
      cannot be turned off. Setting up a magnetic field monitoring device on these
      workers would therefore be a good way to ensure their security. European
      directive threshold adequacy could then be verified. But this verification does
      not ensure a complete analysis of the worker exposure. Such an analysis based on
      quality control charts and exposure time's metrics has been described in this
      paper. The proposed magnetic field exposure analysis has additionally been tested
      on a long-term exposure follow-up of 18 MRI workers during 2 months.

PMID- 28499016
TI  - Minimally Invasive Transforaminal Lumbar Interbody Fusion Using Banana-Shaped and
      Straight Cages: Radiological and Clinical Results from a Prospective Randomized
      Clinical Trial.
AB  - BACKGROUND: In minimally invasive transforaminal lumbar interbody fusion (MIS
      TLIF), cage type and position play important roles in fusion achievement and
      sagittal alignment correction. However, no prospective randomized comparison of
      the results using different types of cage has been reported to date. OBJECTIVE:
      To compare the radiological and clinical outcomes of unilateral MIS-TLIF using 2
      types of cage. METHODS: All candidates for single-level MIS-TLIF were randomized
      into banana-shaped cage and straight-cage groups. Plain radiographs and computed
      tomography scans were used for assessment of cage positions, fusion status, disc
      height, segmental lordotic angle, cage subsidence, and pelvic parameters.
      Clinical outcome was assessed using visual analog scale and Oswestry Disability
      Index scores. RESULTS: Forty-four and 40 consecutive patients were operated on
      using banana-shaped and straight cages, respectively. Cage position was more
      anterior and lateral in the straight-cage group and more medial and posterior in
      the banana-shaped cage group. Solid fusion was achieved in 95.2% and 96.6% of the
      2 groups, respectively, at 12 mo. The change in disc height and segmental
      lordotic angle postoperatively was significantly greater in the banana-shaped
      cage group. The incidence of subsidence during follow-up was significantly higher
      in the banana-shaped cage group (P < .04). Clinically, the visual analog scale
      and Oswestry Disability Index scores decreased significantly after surgery in
      both groups, with no significant difference between the groups. CONCLUSION: Our
      preliminary outcomes suggest that the subsidence rate may be higher using banana
      shaped cages in MIS-TLIF, possibly due to their more medial final position.

PMID- 28499017
TI  - Introduction to the Special Section: Disorders of Sex Development.

PMID- 28499020
TI  - Letter: Rerupture of a Blister Aneurysm After Treatment With a Single Flow
      Diverting Stent.

PMID- 28499019
TI  - T-cadherin gene variants are associated with nephropathy in subjects with type 1
      diabetes.
AB  - Background: High plasma adiponectin levels are associated with diabetic
      nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be
      associated with adiponectin levels. We investigated associations between allelic
      variations of CDH13 and DN in subjects with type 1 diabetes. Methods: Two CDH13
      polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from
      the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up),
      'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and
      'Genetique de la Nephropathie Diabetique' (GENEDIAB) (n = 456, 9-year follow-up
      for n = 283) cohorts. Adiponectin levels were measured in plasma samples from
      GENESIS and GENEDIAB cohorts. Results: Pooled analysis of GENEDIAB and GENESIS
      studies showed that baseline plasma adiponectin levels were higher in subjects
      with established/advanced DN at inclusion (P < 0.0001) and in subjects who
      developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor
      allele of rs3865188 was associated with lower adiponectin levels (P = 0.006).
      rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P =
      0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with
      baseline prevalence of established/advanced DN. These polymorphisms were also
      associated with the risk of ESRD (0.006 < P < 0.03). The association between
      rs11646213 (but not rs3865188) and renal function remained significant after
      adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR)
      1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P =
      0.04) were associated with risk of renal events (defined as progression to more
      severe DN stages). Conclusions: Plasma adiponectin levels are associated with the
      prevalence of DN and the incidence of ESRD in patients with type 1 diabetes.
      CDH13 polymorphisms are also associated with the prevalence and incidence of DN,
      and with the incidence of ESRD in these patients. The association between CDH13
      and DN may be due to pleiotropic effects, both dependent and independent of
      plasma adiponectin levels.

PMID- 28499018
TI  - Intracystic interferon-alpha in pediatric craniopharyngioma patients: an
      international multicenter assessment on behalf of SIOPE and ISPN.
AB  - Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in
      children, presenting predominantly as cystic lesions. Morbidity from conventional
      treatment has focused attention on intracystic drug delivery, hypothesized to
      cause fewer clinical consequences. However, the efficacy of intracystic therapy
      remains unclear. We report the retrospective experiences of several global
      centers using intracystic interferon-alpha. Methods: European Societe
      Internationale d'Oncologie Pediatrique and International Society for Pediatric
      Neurosurgery centers were contacted to submit a datasheet capturing pediatric
      patients with cystic craniopharyngiomas who had received intracystic interferon
      alpha. Patient demographics, administration schedules, adverse events, and
      outcomes were obtained. Progression was clinical or radiological (cyst
      reaccumulation, novel cysts, or solid growth). Results: Fifty-six children
      (median age, 6.3 y) from 21 international centers were identified. Median follow
      up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%)
      or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%)
      patients before interferon use. In such cases, further progression was delayed by
      intracystic interferon compared with the preceding therapy for cystic lesions (P
      = 0.0005). Few significant attributable side effects were reported. Progression
      post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the
      estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7)
      years. Conclusions: Intracystic interferon-alpha can delay disease progression
      and potentially offer a protracted time to definitive surgery or radiotherapy in
      pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile
      compared with other therapeutic modalities-important factors for this developing
      age group. A prospective, randomized international clinical trial assessment is
      warranted.

PMID- 28499021
TI  - Protein-only RNase P function in Escherichia coli: viability, processing defects
      and differences between PRORP isoenzymes.
AB  - The RNase P family comprises structurally diverse endoribonucleases ranging from
      complex ribonucleoproteins to single polypeptides. We show that the organellar
      (AtPRORP1) and the two nuclear (AtPRORP2,3) single-polypeptide RNase P isoenzymes
      from Arabidopsis thaliana confer viability to Escherichia coli cells with a
      lethal knockdown of its endogenous RNA-based RNase P. RNA-Seq revealed that
      AtPRORP1, compared with bacterial RNase P or AtPRORP3, cleaves several precursor
      tRNAs (pre-tRNAs) aberrantly in E. coli. Aberrant cleavage by AtPRORP1 was mainly
      observed for pre-tRNAs that can form short acceptor-stem extensions involving G:C
      base pairs, including tRNAAsp(GUC), tRNASer(CGA) and tRNAHis. However, both
      AtPRORP1 and 3 were defective in processing of E. coli pre-tRNASec carrying an
      acceptor stem expanded by three G:C base pairs. Instead, pre-tRNASec was
      degraded, suggesting that tRNASec is dispensable for E. coli under laboratory
      conditions. AtPRORP1, 2 and 3 are also essentially unable to process the primary
      transcript of 4.5S RNA, a hairpin-like non-tRNA substrate processed by E. coli
      RNase P, indicating that PRORP enzymes have a narrower, more tRNA-centric
      substrate spectrum than bacterial RNA-based RNase P enzymes. The cells' viability
      also suggests that the essential function of the signal recognition particle can
      be maintained with a 5?-extended 4.5S RNA.

PMID- 28499023
TI  - The Chilean Recluse Spider (Araneae: Sicariidae) Displays Behavioral Responses to
      Conspecific Odors, but Not to Several General Odorants.
AB  - Spiders of the family Sicariidae pose a serious threat to affected populations,
      and Loxosceles laeta (Nicolet) is considered the most venomous species.
      Development of nontoxic olfaction-based spider repellents or traps is hindered by
      a current lack of knowledge regarding olfactory system function in arachnids. In
      the present study, general plant odorants and conspecific odors were tested for
      behavioral responses in L. laeta. Although general odorants triggered neither
      attraction nor aversion, conspecific odor of the opposite sex caused aversion in
      females, and attraction in males. These results support the presence of a
      specific olfactory system for the detection of conspecifics in L. laeta, but
      suggest the absence of a broadly tuned system for general odorant detection in
      this species.

PMID- 28499024
TI  - Welcome Editorial by the new NDT Editor-in-Chief.

PMID- 28499022
TI  - Quantitative imaging biomarkers for risk stratification of patients with
      recurrent glioblastoma treated with bevacizumab.
AB  - Background: Anti-angiogenic therapy with bevacizumab is the most widely used
      treatment option for recurrent glioblastoma, but therapeutic response varies
      substantially and effective biomarkers for patient selection are not available.
      To this end, we determine whether novel quantitative radiomic strategies on the
      basis of MRI have the potential to noninvasively stratify survival and
      progression in this patient population. Methods: In an initial cohort of 126
      patients, we identified a distinct set of features representative of the
      radiographic phenotype on baseline (pretreatment) MRI. These selected features
      were evaluated on a second cohort of 165 patients from the multicenter BRAIN
      trial with prospectively acquired clinical and imaging data. Features were
      evaluated in terms of prognostic value for overall survival (OS), progression
      free survival (PFS), and progression within 3, 6, and 9 months using baseline
      imaging and first follow-up imaging at 6 weeks posttreatment initiation. Results:
      Multivariable analysis of features derived at baseline imaging resulted in
      significant stratification of OS (hazard ratio [HR] = 2.5; log-rank P = 0.001)
      and PFS (HR = 4.5; log-rank P = 2.1 * 10-5) in validation data. These
      stratifications were stronger compared with clinical or volumetric covariates
      (permutation test false discovery rate [FDR] <0.05). Univariable analysis of a
      prognostic textural heterogeneity feature (information correlation) derived from
      postcontrast T1-weighted imaging revealed significantly higher scores for
      patients who progressed within 3 months (Wilcoxon test P = 8.8 * 10-8).
      Generally, features derived from postcontrast T1-weighted imaging yielded higher
      prognostic power compared with precontrast enhancing T2-weighted imaging.
      Conclusion: Radiomics provides prognostic value for survival and progression in
      patients with recurrent glioblastoma receiving bevacizumab treatment. These
      results could lead to the development of quantitative pretreatment biomarkers to
      predict benefit from bevacizumab using standard of care imaging.

PMID- 28499026
TI  - Opponent's comments.

PMID- 28499025
TI  - Pro: Risk scores for chronic kidney disease progression are robust, powerful and
      ready for implementation.
AB  - Accurate risk prediction for chronic kidney disease (CKD) progression can inform
      the patient-provider dialogue, and provide actionable thresholds for key clinical
      decisions. In 2011, we developed the kidney failure risk equations (KFREs) to
      predict the risk of kidney failure requiring dialysis or transplant in patients
      with CKD. Subsequently, the KFREs have been extensively validated, and have now
      been proven accurate in multiple continents, ethnicities and disease-specific
      subpopulations. They can discriminate progressors from non-progressors, and are
      well calibrated and easy to use. We believe that current and future studies
      should now focus on clinical implementation of the KFREs, through quality
      improvement initiatives and cluster randomized trials. A risk-based care paradigm
      for CKD care can be achieved through knowledge translation and implementation
      research.

PMID- 28499027
TI  - Farewell Editorial.

PMID- 28499028
TI  - Con: Most clinical risk scores are useless.
AB  - While developing prediction models has become quite popular both in nephrology
      and in medicine in general, most models have not been implemented in clinical
      practice on a larger scale. This should be no surprise, as the majority of
      published models has been shown to be poorly reported and often developed using
      inappropriate methods. The main problems identified relate to either using too
      few candidate predictors (based on univariable P < 0.05) or too many (for the
      number of events), resulting in poorly performing prediction models. Guidelines
      on how to develop and test a prediction model all stress the importance of
      external validation to test discrimination and calibration in other populations,
      as prediction models usually perform less well in new subjects. However, external
      validity has not often been tested for prediction models in renal patients.
      Moreover, impact studies showing improved clinical outcomes when using a
      prediction model in routine clinical practice have been reported rarely. By and
      large, notwithstanding a few notable exceptions like the kidney failure risk
      equation prediction model, most models have not been validated externally or are
      at best inadequately reported, preventing them from be used in clinical practice.
      Therefore, we recommend researchers to spend more energy on validation and
      assessing the impact of existing models, instead of merely developing more models
      that will most likely never be used in clinical practice as well.

PMID- 28499029
TI  - Opponent's comments.

PMID- 28499030
TI  - Moderator's view: Predictive models: a prelude to precision nephrology.
AB  - Appropriate diagnosis is fundamental in medicine because it sets the basis for
      the prediction of disease outcome at the single patient level (prognosis) and
      decisions regarding the most appropriate therapy. However, given the large series
      of social, clinical and biological factors that determine the likelihood of an
      individual's future outcome, prognosis only partly depends on diagnosis and
      aetiology and treatment is not decided solely on the basis of the underlying
      diagnosis. This issue is crucial in multifactorial diseases like atherosclerosis,
      where the use of statins has now shifted from 'treating hypercholesterolaemia' to
      'treating the risk of adverse cardiovascular events'. Approaches that take due
      account of prognosis limit the lingering risk of over-diagnosis and maximize the
      value of prognostic information in the clinical decision process. In the
      nephrology realm, the application of a well-validated risk equation for kidney
      failure in Canada led to a 35% reduction in new referrals. Prognostic models
      based on simple clinical data extractable from clinical files have recently been
      developed to predict all-cause and cardiovascular mortality in end-stage kidney
      disease patients. However, research on predictive models in renal diseases
      remains suboptimal and non-accounting for competing events and measurement
      errors, and a lack of calibration analyses and external validation are common
      fallacies in currently available studies. More focus on this blossoming research
      area is desirable. The nephrology community may now start to apply the best
      validated risk scores and further test their potential usefulness in chronic
      kidney disease patients in diverse clinical situations and geographical areas.

PMID- 28499031
TI  - Primary echinococcus infection of the heart: a rare type of cystic
      echinococcosis.

PMID- 28499032
TI  - Development of a New Tool for Systematic Observation of Nursing Home Resident and
      Staff Engagement and Relationship.
AB  - Purpose of Study: To develop a structured observational tool, the Resident
      centered Assessment of Interactions with Staff and Engagement tool (RAISE), to
      measure 2 critical, multi-faceted, organizational-level aspects of person
      centered care (PCC) in nursing homes: (a) resident engagement and (b) the quality
      and frequency of staff-resident interactions. Design and Methods: In this multi
      method psychometric development study, we conducted (a) 120 hr of ethnographic
      observations in one nursing home and (b) a targeted literature review to enable
      construct development. Two constructs for which no current structured observation
      measures existed emerged from this phase: nursing home resident-staff engagement
      and interaction. We developed the preliminary RAISE to measure these constructs
      and used the tool in 8 nursing homes at an average of 16 times. We conducted 8
      iterative psychometric testing and refinement cycles with multi-disciplinary
      research team members. Each cycle consisted of observations using the draft tool,
      results review, and tool modification. Results: The final RAISE included a set of
      coding rules and procedures enabling simultaneously efficient, non-reactive, and
      representative quantitative measurement of the interaction and engagement
      components of nursing home life for staff and residents. It comprised 8
      observational variables, each represented by extensive numeric codes. Raters
      achieved adequate to high reliability with all variables. There is preliminary
      evidence of face and construct validity via expert panel review. Implications:
      The RAISE represents a valuable step forward in the measurement of PCC, providing
      objective, reliable data based on systematic observation.

PMID- 28499033
TI  - Large-scale recoding of a bacterial genome by iterative recombineering of
      synthetic DNA.
AB  - The ability to rewrite large stretches of genomic DNA enables the creation of new
      organisms with customized functions. However, few methods currently exist for
      accumulating such widespread genomic changes in a single organism. In this study,
      we demonstrate a rapid approach for rewriting bacterial genomes with modified
      synthetic DNA. We recode 200 kb of the Salmonella typhimurium LT2 genome through
      a process we term SIRCAS (stepwise integration of rolling circle amplified
      segments), towards constructing an attenuated and genetically isolated bacterial
      chassis. The SIRCAS process involves direct iterative recombineering of 10-25 kb
      synthetic DNA constructs which are assembled in yeast and amplified by rolling
      circle amplification. Using SIRCAS, we create a Salmonella with 1557 synonymous
      leucine codon replacements across 176 genes, the largest number of cumulative
      recoding changes in a single bacterial strain to date. We demonstrate
      reproducibility over sixteen two-day cycles of integration and parallelization
      for hierarchical construction of a synthetic genome by conjugation. The resulting
      recoded strain grows at a similar rate to the wild-type strain and does not
      exhibit any major growth defects. This work is the first instance of synthetic
      bacterial recoding beyond the Escherichia coli genome, and reveals that
      Salmonella is remarkably amenable to genome-scale modification.

PMID- 28499034
TI  - Functional disability and its predictors in systemic sclerosis: a study from the
      DeSScipher project within the EUSTAR group.
AB  - Objectives: The multisystem manifestations of SSc can greatly impact patients'
      quality of life. The aim of this study was to identify factors associated with
      disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort
      who had completed the scleroderma health assessment questionnaire (SHAQ), a
      disability score that combines the health assessment questionnaire and five
      visual analogue scales, were included in this analysis. The effect of factors
      possibly associated with disability was analysed with multiple linear
      regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included
      were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the
      mild to moderate difficulty SHAQ category (0 ? SHAQ < 1), 34% in the moderate to
      severe disability category (1 ? SHAQ < 2) and 7% in the severe to very severe
      disability category (2 ? SHAQ ? 3). The means of the visual analogue scales
      scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm),
      pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers
      (19 mm). In multiple regression, the main factors associated with high SHAQ
      scores were the presence of dyspnoea [modified New York Heart Association (NYHA)
      class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53)
      and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B =
      0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal
      symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal
      symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital
      ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving
      their level of disability, unlike physicians who emphasize objective measures of
      disability.

PMID- 28499035
TI  - Genetic and Biological Characterization of Four Nucleopolyhedrovirus Isolates
      Collected in Mexico for the Control of Spodoptera exigua (Lepidoptera:
      Noctuidae).
AB  - This study describes four multiple nucleocapsid nucleopolyhedrovirus isolates
      recovered from infected larvae of beet armyworm, Spodoptera exigua (Hubner)
      (Lepidoptera: Noctuidae), on crops in two different geographical regions of
      Mexico. Molecular and biological characterization was compared with characterized
      S. exigua multiple nucleopolyhedrovirus (SeMNPV) isolates from the United States
      (SeUS1 and SeUS2) and Spain (SeSP2). Restriction endonuclease analysis of viral
      DNA confirmed that all Mexican isolates were SeMNPV isolates, but molecular
      differences between the Mexican and the reference isolates were detected using
      PCR combined with restriction fragment length polymorphism (RFLP). Amplification
      of the variable region V01 combined with RFLP distinguished the two Mexican
      isolates, SeSLP6 and SeSIN6. BglII digestions showed that the majority of the
      isolates contained submolar bands, indicating the presence of genetic
      heterogeneity. Amplification of the variable regions V04 and V05 distinguished
      between American and the Spanish isolates. Biological characterization was
      performed against two laboratory colonies of S. exigua, one from Mexico, and
      another from Switzerland. Insects from the Mexican colony were less susceptible
      to infection than insects from Se-Swiss colony. In the Se-Mex colony, SeSP2 was
      the most pathogenic isolate followed by SeSIN6, although their virulence was
      similar to most of the isolates tested. In Se-Swiss colony, similar LD50 values
      were observed for the five isolates, although the virulence was higher for the
      SeSLP6 isolate, which also had the highest OB (occlusion body) yield. We conclude
      that the Mexican isolates SeSIN6 and SeSLP6 possess insecticidal traits of value
      for the development of biopesticides for the control of populations of S. exigua.

PMID- 28499036
TI  - Potential of a Northern Population of Aedes vexans (Diptera: Culicidae) to
      Transmit Zika Virus.
AB  - Zika virus is an emerging arbovirus of humans in the western hemisphere. With its
      potential spread into new geographical areas, it is important to define the
      vector competence of native mosquito species. We tested the vector competency of
      Aedes vexans (Meigen) from the Lake Agassiz Plain of northwestern Minnesota and
      northeastern North Dakota. Aedes aegypti (L.) was used as a positive control for
      comparison. Mosquitoes were fed blood containing Zika virus and 2 wk later were
      tested for viral infection and dissemination. Aedes vexans (n = 60) were
      susceptible to midgut infection (28% infection rate) but displayed a fairly
      restrictive midgut escape barrier (3% dissemination rate). Cofed Ae. aegypti (n =
      22) displayed significantly higher rates of midgut infection (61%) and
      dissemination (22%). To test virus transmission, mosquitoes were inoculated with
      virus and 16-17 d later, tested for their ability to transmit virus into fluid
      filled capillary tubes. Unexpectedly, the transmission rate was significantly
      higher for Ae. vexans (34%, n = 47) than for Ae. aegypti (5%, n = 22). The
      overall transmission potential for Ae. vexans to transmit Zika virus was 1%.
      Because of its wide geographic distribution, often extreme abundance, and
      aggressive human biting activity, Ae. vexans could serve as a potential vector
      for Zika virus in northern latitudes where the conventional vectors, Ae. aegypti
      and Ae. albopictus Skuse, cannot survive. However, Zika virus is a primate virus
      and humans are the only amplifying host species in northern latitudes. To serve
      as a vector of Zika virus, Ae. vexans must feed repeatedly on humans. Defining
      the propensity of Ae. vexans to feed repeatedly on humans will be key to
      understanding its role as a potential vector of Zika virus.

PMID- 28499037
TI  - Ball with hair: modular functionalization of highly stable G-quadruplex DNA nano
      scaffolds through N2-guanine modification.
AB  - Functionalized nanoparticles have seen valuable applications, particularly in the
      delivery of therapeutic and diagnostic agents in biological systems. However, the
      manufacturing of such nano-scale systems with the consistency required for
      biological application can be challenging, as variation in size and shape have
      large influences in nanoparticle behavior in vivo. We report on the development
      of a versatile nano-scaffold based on the modular functionalization of a DNA G
      quadruplex. DNA sequences are functionalized in a modular fashion using well
      established phosphoramidite chemical synthesis with nucleotides containing
      modification of the amino (N2) position of the guanine base. In physiological
      conditions, these sequences fold into well-defined G-quadruplex structures. The
      resulting DNA nano-scaffolds are thermally stable, consistent in size, and
      functionalized in a manner that allows for control over the density and relative
      orientation of functional chemistries on the nano-scaffold surface. Various
      chemistries including small modifications (N2-methyl-guanine), bulky aromatic
      modifications (N2-benzyl-guanine), and long chain-like modifications (N2-6-amino
      hexyl-guanine) are tested and are found to be generally compatible with G
      quadruplex formation. Furthermore, these modifications stabilize the G-quadruplex
      scaffold by 2.0-13.3  degrees C per modification in the melting temperature, with
      concurrent modifications producing extremely stable nano-scaffolds. We
      demonstrate the potential of this approach by functionalizing nano-scaffolds for
      use within the biotin-avidin conjugation approach.

PMID- 28499039
TI  - Scrofula.

PMID- 28499038
TI  - Functional characterization and architecture of recombinant yeast SWR1 histone
      exchange complex.
AB  - We have prepared recombinant fourteen subunit yeast SWR1 complex from insect
      cells using a modified MultiBac system. The 1.07 MDa recombinant protein complex
      has histone-exchange activity. Full exchange activity is realized with a single
      SWR1 complex bound to a nucleosome. We also prepared mutant complexes that lack a
      variety of subunits or combinations of subunits and these start to reveal roles
      for some of these subunits as well as indicating interactions between them in the
      full complex. Complexes containing a series of N-terminally and C-terminally
      truncated Swr1 subunits reveal further details about interactions between
      subunits as well as their binding sites on the Swr1 subunit. Finally, we present
      electron microscopy studies revealing the dynamic nature of the complex and a 21
      A resolution reconstruction of the intact complex provides details not apparent
      in previously reported structures, including a large central cavity of sufficient
      size to accommodate a nucleosome.

PMID- 28499040
TI  - Evolving gene banks: improving diverse populations of crop and exotic germplasm
      with optimal contribution selection.
AB  - We simulated pre-breeding in evolving gene banks - populations of exotic and crop
      types undergoing optimal contribution selection for long-term genetic gain and
      management of population genetic diversity. The founder population was based on
      crosses between elite crop varieties and exotic lines of field pea (Pisum
      sativum) from the primary genepool, and was subjected to 30 cycles of recurrent
      selection for an economic index composed of four traits with low heritability:
      black spot resistance, flowering time and stem strength (measured on single
      plants), and grain yield (measured on whole plots). We compared a small
      population with low selection pressure, a large population with high selection
      pressure, and a large population with moderate selection pressure. Single seed
      descent was compared with S0-derived recurrent selection. Optimal contribution
      selection achieved higher index and lower population coancestry than truncation
      selection, which reached a plateau in index improvement after 40 years in the
      large population with high selection pressure. With optimal contribution
      selection, index doubled in 38 years in the small population with low selection
      pressure and 27-28 years in the large population with moderate selection
      pressure. Single seed descent increased the rate of improvement in index per
      cycle but also increased cycle time.

PMID- 28499041
TI  - Nature's pulse power: legumes, food security and climate change.

PMID- 28499042
TI  - Proteomic analysis reveals changes in carbohydrate and protein metabolism
      associated with broiler breast myopathy.
AB  - White Striping (WS) and Woody Breast (WB) are 2 conditions that adversely affect
      consumer acceptance as well as quality of poultry meat and meat products. Both WS
      and WB are characterized with degenerative myopathic changes. Previous studies
      showed that WS and WB in broiler fillets could result in higher ultimate pH,
      increased drip loss, and decreased marinade uptake. The main objective of the
      present study was to compare the proteomic profiles of muscle tissue (n = 5 per
      group) with either NORM (no or few minor myopathic lesions) or SEV (with severe
      myopathic changes). Proteins were extracted from these samples and analyzed using
      a hybrid LTQ-OrbitrapXL mass spectrometer (LC-MS/MS). Over 800 proteins were
      identified in the muscle samples, among which 141 demonstrated differential (P <
      0.05) expression between NORM and SEV. The set of differentially (P < 0.05)
      expressed proteins was uploaded to Ingenuity Pathway Analysis(r) (IPA) software
      to determine the associated biological networks and pathways. The IPA analysis
      showed that eukaryotic initiation factor-2 (eIF-2) signaling, mechanistic target
      of rapamycin (mTOR) signaling, as well as regulation of eIF4 and p70S6K signaling
      were the major canonical pathways up-regulated (P < 0.05) in SEV muscle compared
      to NORM. The up-regulation of these pathways indicate an increase in protein
      synthesis which could be part of the rapid growth as well as cellular stress
      associated with ongoing muscle degeneration and the attempt to repair tissue
      damage in SEV birds. Furthermore, IPA analysis revealed that glycolysis and
      gluconeogenesis were the major down-regulated (P < 0.05) canonical pathways in
      SEV with respect to NORM muscle. Down-regulation of these pathways could be the
      reason for higher ultimate pH seen in SEV muscle samples indicating reduced
      glycolytic potential. In conclusion, comparison of proteomic profiles of NORM and
      SEV muscle samples showed differences in protein profile which explains some of
      the observed differences in meat quality parameters. Future studies based on
      these differences could provide valuable insights into various cellular changes
      and identification of biomarkers related to WS and WB.

PMID- 28499043
TI  - Bioethics and Transhumanism.
AB  - Transhumanism is a "technoprogressive" socio-political and intellectual movement
      that advocates for the use of technology in order to transform the human organism
      radically, with the ultimate goal of becoming "posthuman." To this end,
      transhumanists focus on and encourage the use of new and emerging technologies,
      such as genetic engineering and brain-machine interfaces. In support of their
      vision for humanity, and as a way of reassuring those "bioconservatives" who may
      balk at the radical nature of that vision, transhumanists claim common ground
      with a number of esteemed thinkers and traditions, from the ancient philosophy of
      Plato and Aristotle to the postmodern philosophy of Nietzsche. It is crucially
      important to give proper scholarly attention to transhumanism now, not only
      because of its recent and ongoing rise as a cultural and political force (and the
      concomitant potential ramifications for bioethical discourse and public policy),
      but because of the imminence of major breakthroughs in the kinds of technologies
      that transhumanism focuses on. Thus, the articles in this issue of The Journal of
      Medicine and Philosophy are either explicitly about transhumanism or are on
      topics, such as the ethics of germline engineering and criteria for personhood,
      that are directly relevant to the debate between transhumanists (and
      technoprogressives more broadly) and bioconservatives.

PMID- 28499044
TI  - Determinants of decline of renal function in treated hypertensive patients: the
      Campania Salute Network.
AB  - Background: Hypertension is a leading cause of chronic kidney disease (CKD) and a
      decrease in glomerular filtration rate (GFR) is associated with a higher
      prevalence of hypertension and an increased proportion of suboptimal blood
      pressure (BP) control. Methods: To investigate characteristics associated with
      GFR decline, we selected 4539 hypertensive patients from the Campania Salute
      Network (mean age 53 +/- 11 years) with at least 3 years of follow-up (FU) and no
      more than Stage III CKD. GFR was calculated at baseline and at the last available
      visit using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation. GFR decline was defined as a >=30% decrease from initial GFR for
      patients in Stage III CKD or by a composite >=30% decrease from baseline and a
      final value of <60 for those < with Stage III or higher CKD. Results: At a mean
      FU of 7.5 years, 432 patients (10%) presented with GFR decline. Those patients
      were older, more likely to be diabetic, with lower GFR and ejection fraction,
      higher systolic and lower diastolic BP and higher left ventricular (LV) mass and
      relative wall thickness at baseline; during FU, patients with GFR decline
      exhibited higher systolic BP, took more drugs and developed more atrial
      fibrillation (all P < 0.02). The probability of GFR decline was independently
      associated with older age, prevalent diabetes, baseline lower GFR, higher
      systolic BP during FU, FU duration, increased LV mass and incident AF with no
      impact from antihypertensive and antiplatelet medications. Conclusions: During
      antihypertensive therapy, kidney function declines in patients with initially
      lower GFR, increased LV mass and suboptimal BP control during FU.

PMID- 28499045
TI  - Challenges Facing Today's Families and Why Social Work Matters.

PMID- 28499046
TI  - Letter to the Editor: Very Late Reactivation of Retinopathy of Prematurity After
      Monotherapy With Intravitreal Bevacizumab.

PMID- 28499047
TI  - Current Treatment Options for the Management of Vitreomacular Traction.

PMID- 28499048
TI  - Three Different Optical Coherence Tomography Angiography Measurement Methods for
      Assessing Capillary Density Changes in Diabetic Retinopathy.
AB  - BACKGROUND AND OBJECTIVE: To compare capillary density (CD) changes assessed by
      optical coherence tomography angiography (OCTA) during diabetic retinopathy (DR)
      progression using three previously published methods: binarization,
      skeletonization, and automated flow density (AFD). PATIENTS AND METHODS:
      Retrospective study of 98 eyes of 74 patients with diabetes and 18 control eyes
      imaged using OCTA. The macular CD at each stage of DR was assessed using the
      three methods and were compared to control eyes. RESULTS: AFD was the only method
      that detected differences between controls and severe nonproliferative DR eyes.
      The three methods showed a significant difference in CD between controls and eyes
      with proliferative DR, except for the "fovea" area. CONCLUSION: Only one of the
      three methods allowed for the detection of changes from the normal capillary
      density as early as at the "severe nonproliferative DR" stage due to several
      refinements from the basic technique. [Ophthalmic Surg Lasers Imaging Retina.
      2017;48:378-384.].

PMID- 28499049
TI  - Quantitative Comparison of Swept-Source and Spectral-Domain OCT Angiography in
      Healthy Eyes.
AB  - BACKGROUND AND OBJECTIVE: To compare macular vessel density (VD) and foveal
      avascular zone (FAZ) area in healthy individuals using two different optical
      coherence tomography angiography (OCTA) devices. PATIENTS AND METHODS: In this
      prospective, comparative study, 25 eyes of 14 healthy subjects underwent fovea
      centered 3 mm * 3 mm OCTA-imaging using the Triton (Topcon, Tokyo, Japan) and RS
      3000 (Nidek, Gamagori, Japan) OCTA devices. Superficial and deep retinal layers
      (SRL/DRL) and FAZ were manually graded after threshold standardization to
      determine macular VD and area of the FAZ. RESULTS: The mean difference in the VD
      between the two devices was 0.105 and 0.096, and the coefficient of variation
      (CV) was 19.59% and 16.90% for the SRL and DRL, respectively. After
      skeletonization of vessels to remove variation related to vessel width, the mean
      difference was 0.174 mm-1 and 0.516 mm-1, and the CV was 3.49% and 1.07% for SRL
      and DRL, respectively. The mean difference of FAZ area was 0.001 mm2 and 0.010
      mm2 in the SRL and DRL, respectively, and the CV was 2.17% and 5.74% for the SRL
      and DRL, respectively. CONCLUSION: Macular VD using skeletonized mapping and FAZ
      area in SRL and DRL were statistically similar between the two devices,
      demonstrating a possible comparison of quantitative values between different OCTA
      devices. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:385-391.].

PMID- 28499050
TI  - Swept-Source OCT Visualization of Macular Hole Closure in Gas-Filled Eyes.
AB  - BACKGROUND AND OBJECTIVE: To assess the utility of swept-source optical coherence
      tomography (SS-OCT) in visualizing macular hole (MH) closure through gas-filled
      eyes on postoperative day (POD) 1 using a dual scanning protocol. PATIENTS AND
      METHODS: We examined 30 consecutive patients with full-thickness MH who underwent
      standard vitrectomy with SF6 (25%) gas tamponade between July 2015 and April
      2016. SS-OCT imaging was performed using horizontal raster and 16-line radial
      scans with manual delicate focusing to evaluate MH closure status. RESULTS: On
      POD1, optically clear images with visualization of all retinal layers at the
      fovea were obtained in 80% of eyes, of which 71% achieved complete MH closure.
      Reasons for unsuccessful imaging included: hyphema (two eyes), dense cataract
      (two eyes), and gas meniscus interference (two eyes). CONCLUSION: SS-OCT with
      dual scanning protocol and manual delicate focusing enabled consistent early
      visualization of foveal architecture for assessment of MH closure through gas
      filled eyes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:392-398.].

PMID- 28499051
TI  - Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic
      Macular Edema.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of ziv-aflibercept
      (Zaltrap; Sanofi-Aventis, Bridgewater, NJ/Regeneron Pharmaceuticals, Tarrytown,
      NY) in the treatment of refractory diabetic macular edema (DME). PATIENTS AND
      METHODS: Retrospective case series looking at the safety of ziv-aflibercept in
      patients with DME refractory to previous anti-vascular endothelial growth factor
      (VEGF) therapy. Detailed ophthalmologic examination, best-corrected visual
      acuity, and optical coherence tomography measurements were performed pre-switch,
      as well as at each monthly follow-up visit. RESULTS: The study included 34 eyes
      of 26 patients. The mean number of ziv-aflibercept injections post-switch was
      2.03 injections. Visual acuity improved from a mean of 0.63 logMAR pre-switch to
      0.51 logMAR after the first visit and 0.46 logMAR after the second visit post
      switch (P < .084). Macular thickness improved from a mean of 513.79 MUm to 411.79
      MUm (P = .006) on the first visit and 426.76 MUm (P = .029) after the second
      visit post-switch. No adverse ocular or systemic side effects were reported on
      any of the follow visits. CONCLUSION: Ziv-aflibercept appears to be safe and
      effective in patients with refractory DME previously treated with other anti-VEGF
      agents in the short term. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:399
      405.].

PMID- 28499052
TI  - Outcomes of 27-Gauge Vitrectomy-Assisted Choroidal and Subretinal Biopsy.
AB  - BACKGROUND AND OBJECTIVE: To report the initial experience of 27-gauge vitrectomy
      assisted choroidal and subretinal biopsy PATIENTS AND METHODS: Retrospective,
      interventional case series. Eighteen eyes of 18 patients undergoing 27-gauge
      vitrectomy-assisted choroidal (n = 16) or subretinal biopsy (n = 2). Clinical and
      lesion characteristics, cytopathology, histology, gene expression profiling
      (GEP), visual acuity (VA), complications including vitreous hemorrhage (VH),
      development of rhegmatogenous retinal detachment (RD), and need for additional
      surgeries were analyzed. RESULTS: Indications were choroidal melanoma (n = 10),
      indeterminate choroidal (n = 5), and subretinal lesions (n = 3). Mean lesion
      height was 3.33 mm +/- 1.55 mm (range: 0.80 mm to 6.75 mm) and largest diameter
      was 8.63 mm +/- 4.14 mm (range: 3 mm to 15.5 mm). Mean number of intralesional
      biopsy passes required was 1.76 +/- 0.83 (range: one to four). During a mean
      follow-up of 7.4 months +/- 2.7 months (range: 4 months to 14 months), VA was
      unchanged (0.5 logMAR +/- 0.6 logMAR vs. 0.7 logMAR +/- 0.84 logMAR; P = .07).
      Pathologic diagnosis was obtained in 16 of 18 eyes (88.9%), and GEP data were
      collected for all 11 choroidal melanomas. Post-biopsy VH occurred in 13 of 18
      eyes (72.2%) and was severe enough to require a concurrent limited vitrectomy in
      six eyes (33.3%). These eyes had a greater lesion height compared to eyes not
      requiring a vitrectomy (4.08 mm +/- 1.68 mm vs. 2.76 mm +/- 1.43 mm; P = .04). A
      rhegmatogenous RD requiring repeat surgery developed in two of 18 eyes (11.1%).
      CONCLUSION: The authors concluded that 27-gauge vitrectomy-assisted choroidal and
      subretinal biopsy established a diagnosis in 88.9% of eyes in lesions 0.8 mm or
      larger. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:406-415.].

PMID- 28499053
TI  - A Modified Perfluoro-n-octane-Assisted Autologous Internal Limiting Membrane
      Transplant for Failed Macular Hole Reintervention: A Case Series.
AB  - The authors describe a modified perfluoro-n-octane (PFO)-assisted autologous
      internal limiting membrane (ILM) transplantation technique for macular hole (MH)
      reintervention and present results from a series of 11 patients. The authors
      harvested a free ILM flap and transplanted it into the MH under a PFO bubble. The
      time at which PFO is injected, the extent of coverage of PFO, and the sequence of
      fluid-air exchange (FAE) are crucial to overcome previously described technical
      difficulties of relieving the flap from forceps, stabilizing the flap into the
      MH, and prevention of flap dislodgement during FAE. A successful U-shaped closure
      was observed in 10 of 11 cases (90.9%). One case (9.1%) showed flat open closure.
      The postoperative visual gain was statistically significant (P = .01).
      [Ophthalmic Surg Lasers Imaging Retina. 2017;48:416-420.].

PMID- 28499054
TI  - Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic
      Calcifications Using a Nitinol Loop: A Case Series.
AB  - Deposition of dystrophic calcifications on the posterior surface of silicone
      intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis.
      Accumulation of silicone oil droplets on the posterior surface of silicone IOLs
      in silicone-filled eyes has also been reported. Recently, a novel technique to
      manually remove dystrophic calcifications using a nickel titanium loop (Finesse
      Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL
      exchange. Here, the authors report their outcomes with this technique in five
      eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil
      droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].

PMID- 28499055
TI  - Sequential Sterile Intraocular Inflammation Associated With Consecutive
      Intravitreal Injections of Aflibercept and Ranibizumab.
AB  - The authors report the unique response of two patients treated for cystoid
      macular edema (CME) secondary to central retinal vein occlusion (CRVO) who
      developed sequential episodes of likely sterile inflammatory responses following
      separate intravitreal injections of aflibercept (Eylea; Regeneron, Tarrytown, NY)
      and ranibizumab (Lucentis; Genentech, South San Francisco, CA) despite multiple
      previous uneventful injections for CME secondary to CRVO. Following the twenty
      fifth aflibercept and seventh ranibizumab injection, two patients developed an
      acute inflammatory response, which was treated empirically with intravitreal
      antibiotics and topical and oral steroids (in Case 2). After an 8- to 10-week
      hiatus, they were switched over to ranibizumab and aflibercept, respectively,
      following which they developed a second episode of intraocular inflammation,
      treated similarly. Vitreous culture in one and aqueous culture in the other were
      deemed to represent contamination. Sterile intraocular inflammation, a known risk
      following injection with either aflibercept or ranibizumab, may develop
      sequentially in the same patient despite switching the drug. [Ophthalmic Surg
      Lasers Imaging Retina. 2017;48:428-431.].

PMID- 28499056
TI  - Recurrent Macular Detachment Due to Occult Retinal Break in a Patient With Optic
      Disc Pit.
AB  - Serous macular detachment occurs in nearly 50% of eyes with optic disc pit. These
      macular detachments have been historically difficult to treat. The authors report
      a case of macular retinal detachment due to an occult juxtapapillary retinal
      break in a patient with optic disc pit refractory to prior treatments. This case
      demonstrates that a presumed serous detachment associated with an optic disc pit
      may have a rhegmatogenous etiology. [Ophthalmic Surg Lasers Imaging Retina.
      2017;48:432-434.].

PMID- 28499057
TI  - Adaptive Optics Scanning Laser Ophthalmoscopy and Multimodal Imaging of Peau
      D'Orange in Pseudoxanthoma Elasticum.
AB  - A 41-year-old male with pseudoxanthoma elasticum who presented with progressive
      vision loss in his left periphery is discussed. Bilateral angioid streaks, optic
      disc drusen, choroidal neovascularization, and peau d'orange were present.
      Imaging of the area with peau d'orange with adaptive optics scanning laser
      ophthalmoscopy and en face optical coherence tomography at Bruch's membrane (BM)
      revealed a pattern identical to the patches of peau d'orange visible with
      conventional fundus imaging techniques. These results show that structural
      abnormalities at the level of BM, likely a result of calcification, correlate
      with the characteristic "orange peel" pattern known as peau d'orange. [Ophthalmic
      Surg Lasers Imaging Retina. 2017;48:436-440.].

PMID- 28499058
TI  - Association of Myelinated Retinal Nerve Fibers With Acquired Mulberry Retinal
      Astrocytoma: Coincidental or Relational?
AB  - Retinal astrocytoma is an important ocular finding for diagnosis of tuberous
      sclerosis complex and is also an association of neurofibromatosis. The authors
      present findings of a case of acquired astrocytoma associated with myelinated
      retinal nerve fibers. The authors also discuss the images and possible cause
      effect relationship between them. [Ophthalmic Surg Lasers Imaging Retina.
      2017;48:441-442.].

PMID- 28499059
TI  - 8 Questions with Darius Moshfeghi.

PMID- 28499060
TI  - Follow-up of tinea capitis with trichoscopy: a prospective clinical study.

PMID- 28499061
TI  - Primary skin manifestation of plasmoblastic lymphoma in an AIDS patient with long
      term survival.

PMID- 28499062
TI  - Compound annotation in liquid chromatography/high-resolution mass spectrometry
      based metabolomics: robust adduct ion determination as a prerequisite to
      structure prediction in electrospray ionization mass spectra.
AB  - RATIONALE: A bottleneck in metabolic profiling of complex biological extracts is
      confident, non-supervised annotation of ideally all contained, chemically highly
      diverse small molecules. Recent computational strategies combining sum formula
      prediction with in silico fragmentation achieve confident de novo annotation,
      once the correct neutral mass of a compound is known. Current software solutions
      for automated adduct ion assignment, however, are either publicly unavailable or
      have been validated against only few experimental electrospray ionization (ESI)
      mass spectra. METHODS: We here present findMAIN (find Main Adduct IoN), a new
      heuristic approach for interpreting ESI mass spectra. findMAIN scores MS1 spectra
      based on explained intensity, mass accuracy and isotope charge agreement of
      adducts and related ionization products and annotates peaks of the (de)protonated
      molecule and adduct ions. The approach was validated against 1141 ESI positive
      mode spectra of chemically diverse standard compounds acquired on different high
      resolution mass spectrometric instruments (Orbitrap and time-of-flight).
      Robustness against impure spectra was evaluated. RESULTS: Correct adduct ion
      assignment was achieved for up to 83% of the spectra. Performance was independent
      of compound class and mass spectrometric platform. The algorithm proved highly
      tolerant against spectral contamination as demonstrated exemplarily for co
      eluting compounds as well as systematically by pairwise mixing of spectra. When
      used in conjunction with MS-FINDER, a state-of-the-art sum formula tool, correct
      sum formulas were obtained for 77% of spectra. It outperformed both 'brute force'
      approaches and current state-of-the-art annotation packages tested as potential
      alternatives. Limitations of the heuristic pertained to poorly ionizing compounds
      and cationic compounds forming [M]+ ions. CONCLUSIONS: A new, validated approach
      for interpreting ESI mass spectra is presented, filling a gap in the nontargeted
      metabolomics workflow. It is freely available in the latest version of R package
      InterpretMSSpectrum.

PMID- 28499064
TI  - Enhancing auxin accumulation in maize root tips improves root growth and dwarfs
      plant height.
AB  - Maize is a globally important food, feed crop and raw material for the food and
      energy industry. Plant architecture optimization plays important roles in maize
      yield improvement. PIN-FORMED (PIN) proteins are important for regulating auxin
      spatiotemporal asymmetric distribution in multiple plant developmental processes.
      In this study, ZmPIN1a overexpression in maize increased the number of lateral
      roots and inhibited their elongation, forming a developed root system with longer
      seminal roots and denser lateral roots. ZmPIN1a overexpression reduced plant
      height, internode length and ear height. This modification of the maize phenotype
      increased the yield under high-density cultivation conditions, and the developed
      root system improved plant resistance to drought, lodging and a low-phosphate
      environment. IAA concentration, transport capacity determination and application
      of external IAA indicated that ZmPIN1a overexpression led to increased IAA
      transport from shoot to root. The increase in auxin in the root enabled the plant
      to allocate more carbohydrates to the roots, enhanced the growth of the root and
      improved plant resistance to environmental stress. These findings demonstrate
      that maize plant architecture can be improved by root breeding to create an ideal
      phenotype for further yield increases.

PMID- 28499065
TI  - Not sick enough: Experiences of carers of people with mental illness negotiating
      care for their relatives with mental health services.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Existing literature provides insight into the
      general experience of carers of people with a mental illness. Previous studies
      have found that carers experience a range of emotions when looking after their
      relatives with a mental illness. However, experiences of carers as they engage
      with the healthcare system is largely absent from the literature. WHAT THIS PAPER
      ADDS TO EXISTING KNOWLEDGE?: This paper identified the experiences of carers when
      their relatives are experiencing a crisis or acutely unwell. Carers found
      themselves in the middle between mental health services and their relatives.
      Strategies employed by carers to ensure their relatives receive adequate care
      were identified from this study. This paper identified how carers needed to
      become more assertive in order to receive adequate care for their relatives, and
      this finding has implications for any future carer education. WHAT ARE THE
      IMPLICATIONS FOR PRACTICE?: The participants identified the need to work more
      collaboratively with carers of people with a mental illness as they seek
      treatment for their relatives in order to achieve better health outcomes for the
      patients. Improved health service engagement of carers was seen by participants
      to assist them to better care for their relative. The study also found that there
      needs to be a clearer definition as to what constitutes mental health crisis and
      how carers are able to intervene during this period. Services could provide clear
      information concerning crisis services and in particular triage. ABSTRACT: Aim
      The literature reporting experiences of relatives of people with mental illness
      regarding their interactions with mental health services identifies many
      commonalities. However, the actual experience of carers engaging the services and
      understanding healthcare systems remains a gap in the literature. The aim of this
      study was to explore the experiences of carers (of people with a severe mental
      illness) in a major area mental health service in Victoria Australia as they
      fulfil their caring role while negotiating support for their relative. A carer is
      defined as a family member or significant other who is the primary individual who
      provides informal care for a person with severe mental illness and may or may not
      be in receipt of income supplement for such a role. Specifically this study has a
      focus on the experience of the carer when negotiating care needs or admission
      with a mental health service. Method A qualitative descriptive approach was used
      with five focus groups as a means of data collection. Ethical approval for the
      study was obtained from both the hospital and universities ethics committees.
      Results Key themes identified using thematic analysis are presented in the words
      of the carers and include: "Juggling" between services; We became assertive and
      If only they would listen. Often carers were advocating for their relative and
      needing to negotiate between services (police and crisis assessment teams) to
      gain any form of assessment or intervention. Carers often spent a great deal of
      time on the phone to services only to be told that their relative was "not sick
      enough" to access care or that no response would occur without another service
      also being involved. Discussion Our research highlights the importance of working
      collaboratively with informal carers and acknowledging their valuable
      contribution to the care of their relatives with a severe mental illness. It is
      very important that adequate support is given to carers especially during the
      period when their relatives are experiencing a crisis. An understanding of their
      experiences ensures a more family focused approach towards care. The study
      findings should enable the healthcare team to focus attention on the issues which
      are most pertinent to carers. Nurses are advocates not only for the patient but
      also for their families. Relevance statement Carers supporting a person who
      experiences mental illness can often find themselves in difficult and emotionally
      challenging situations such as at times of crisis and admission to mental health
      services. The fourth and latest Australian National Mental Health Plan (2009
      2014) acknowledged these concerns and highlighted the need to recognize the role
      of carers in promoting well-being and recovery of the relative with a mental
      illness. The plan acknowledges that families are often best placed to recognize
      signs of relapse in their family members with a mental illness and discharge
      planning should include the involvement of family members (Commonwealth of
      Australia, ). To achieve best care outcomes for consumers, mental health nurses
      need to recognize the role of the carer and collaborate in care planning.

PMID- 28499063
TI  - High efficient multisites genome editing in allotetraploid cotton (Gossypium
      hirsutum) using CRISPR/Cas9 system.
AB  - Gossypium hirsutum is an allotetraploid with a complex genome. Most genes have
      multiple copies that belong to At and Dt subgenomes. Sequence similarity is also
      very high between gene homologues. To efficiently achieve site/gene-specific
      mutation is quite needed. Due to its high efficiency and robustness, the CRISPR
      (clustered regularly interspaced short palindromic repeats)/Cas9 system has
      exerted broad site-specific genome editing from prokaryotes to eukaryotes. In
      this study, we utilized a CRISPR/Cas9 system to generate two sgRNAs in a single
      vector to conduct multiple sites genome editing in allotetraploid cotton. An
      exogenously transformed gene Discosoma red fluorescent protein2(DsRed2) and an
      endogenous gene GhCLA1 were chosen as targets. The DsRed2-edited plants in T0
      generation reverted its traits to wild type, with vanished red fluorescence the
      whole plants. Besides, the mutated phenotype and genotype were inherited to their
      T1 progenies. For the endogenous gene GhCLA1, 75% of regenerated plants exhibited
      albino phenotype with obvious nucleotides and DNA fragments deletion. The
      efficiency of gene editing at each target site is 66.7-100%. The mutation
      genotype was checked for both genes with Sanger sequencing. Barcode-based high
      throughput sequencing, which could be highly efficient for genotyping to a
      population of mutants, was conducted in GhCLA1-edited T0 plants and it matched
      well with Sanger sequencing results. No off-target editing was detected at the
      potential off-target sites. These results prove that the CRISPR/Cas9 system is
      highly efficient and reliable for allotetraploid cotton genome editing.

PMID- 28499066
TI  - Perceiving social pressure not to feel negative predicts depressive symptoms in
      daily life.
AB  - BACKGROUND: Western societies often overemphasize the pursuit of happiness, and
      regard negative feelings such as sadness or anxiety as maladaptive and unwanted.
      Despite this emphasis on happiness, the amount of people suffering from
      depressive complaints is remarkably high. To explain this apparent paradox, we
      examined whether experiencing social pressure not to feel sad or anxious could in
      fact contribute to depressive symptoms. METHODS: A sample of individuals (n =
      112) with elevated depression scores (Patient Health Questionnaire [PHQ-9] >= 10)
      took part in an online daily diary study in which they rated their depressive
      symptoms and perceived social pressure not to feel depressed or anxious for 30
      consecutive days. Using multilevel VAR models, we investigated the temporal
      relation between this perceived social pressure and depressive symptoms to
      determine directionality. RESULTS: Primary analyses consistently indicated that
      experiencing social pressure predicts increases in both overall severity scores
      and most individual symptoms of depression, but not vice versa. A set of
      secondary analyses, in which we adopted a network perspective on depression,
      confirmed these findings. Using this approach, centrality analysis revealed that
      perceived social pressure not to feel negative plays an instigating role in
      depression, reflected by the high out- and low instrength centrality of this
      pressure in the various depression networks. CONCLUSIONS: Together, these
      findings indicate how perceived societal norms may contribute to depression,
      hinting at a possible malignant consequence of society's denouncement of negative
      emotions. Clinical implications are discussed.

PMID- 28499067
TI  - Nitrogen and Fluorine-Codoped Carbon Nanowire Aerogels as Metal-Free
      Electrocatalysts for Oxygen Reduction Reaction.
AB  - The development of active, durable, and low-cost catalysts to replace noble metal
      based materials is highly desirable to promote the sluggish oxygen reduction
      reaction in fuel cells. Herein, nitrogen and fluorine-codoped three-dimensional
      carbon nanowire aerogels, composed of interconnected carbon nanowires, were
      synthesized for the first time by a hydrothermal carbonization process. Owing to
      their porous nanostructures and heteroatom-doping, the as-prepared carbon
      nanowire aerogels, with optimized composition, present excellent electrocatalytic
      activity that is comparable to commercial Pt/C. Remarkably, the aerogels also
      exhibit superior stability and methanol tolerance. This synthesis procedure paves
      a new way to design novel heteroatom-doped catalysts.

PMID- 28499068
TI  - MutMapPlus identified novel mutant alleles of a rice starch branching enzyme IIb
      gene for fine-tuning of cooked rice texture.
AB  - Physicochemical properties of storage starch largely determine rice grain quality
      and food characteristics. Therefore, modification of starch property is effective
      to fine-tune cooked rice textures. To obtain new resources with modified starch
      property as breeding materials, we screened a mutant population of a japonica
      cultivar Nipponbare and found two independent mutant lines, altered
      gelatinization (age)1 and age2, with moderate changes in starch gelatinization
      property. A combination of conventional genetic analyses and the latest mapping
      method, MutMapPlus, revealed that both of these lines harbour novel independent
      mutant alleles of starch branching enzyme IIb (BEIIb) gene. In age1, amino acid
      substitution of Met-723 to Lys completely abolished BEIIb enzyme activity without
      significant reduction in its protein level. A transposon insertion in an intron
      of BEIIb gene reduced BEIIb protein level and activity in age2. Production of a
      series of the mutant lines by combining age alleles and indica-type starch
      synthase IIa allele established stepwise alteration of the physicochemical
      properties of starch including apparent amylose content, thermal property,
      digestibility by alpha-amylase and branched structures of amylopectin. Consistent
      with the alteration of starch properties, the results of a sensory evaluation
      test demonstrated that warm cooked rice of the mutants showed a variety of
      textures without marked reduction in overall palatability. These results suggest
      that a series of the mutant lines are capable of manipulation of cooked rice
      textures.

PMID- 28499070
TI  - Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic
      hepatitis C after achievement of virologic response.
AB  - It is unclear whether the achievement of virologic response modifies the risk of
      hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and
      chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between
      patients with CHB and CHC who achieved virological response. We analysed data
      from patients with CHB treated with entecavir (n=2000) or CHC treated with peg
      interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011.
      Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment
      for CHB or the achievement of sustained virologic response for CHC. Virological
      response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC
      (64.8%). During the median follow-up period of 6 years, 228 patients with CHB
      (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with
      virological response, CHB was independently associated with a significantly
      higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30-3.63; P=.003) than CHC.
      Among patients without virological response, there were no differences in HCC
      incidence between the two cohorts (P=.52). In patients with cirrhosis at
      baseline, the incidence of HCC did not differ between the two cohorts even after
      achieving virological response (P>.99). In conclusion, patients with CHB treated
      with entecavir were associated with a higher risk of HCC compared to patients
      with CHC treated with peg-interferon and ribavirin after achieving virological
      response. However, the risk of HCC did not differ between the two cohorts if the
      patients had cirrhosis at baseline, even if virological response was achieved.

PMID- 28499069
TI  - The association of hormone signalling genes, transcription and changes in shoot
      anatomy during moso bamboo growth.
AB  - Moso bamboo is a large, woody bamboo with the highest ecological, economic and
      cultural value of all the bamboo types and accounts for up to 70% of the total
      area of bamboo grown. However, the spatiotemporal variation role of moso bamboo
      shoot during growth period is still unclear. We found that the bamboo shoot
      growth can be divided into three distinct periods, including winter growth, early
      growth and late growth based on gene expression and anatomy. In the early growth
      period, lateral buds germinated from the top of the bamboo joint in the shoot
      tip. Intercalary meristems grew vigorously during the winter growth period and
      early growth period, but in the late growth period, mitosis in the intercalary
      meristems decreased. The expression of cell cycle-associated genes and the
      quantity of differentially expressed genes were higher in early growth than those
      in late growth, appearing to be influenced by hormonal concentrations. Gene
      expression analysis indicates that hormone signalling genes play key roles in
      shoot growth, while auxin signalling genes play a central role. In situ
      hybridization analyses illustrate how auxin signalling genes regulate apical
      dominance, meristem maintenance and lateral bud development. Our study provides a
      vivid picture of the dynamic changes in anatomy and gene expression during shoot
      growth in moso bamboo, and how hormone signalling-associated genes participate in
      moso bamboo shoot growth.

PMID- 28499071
TI  - Natural Abundance 17 O DNP NMR Provides Precise O-H Distances and Insights into
      the Bronsted Acidity of Heterogeneous Catalysts.
AB  - Heterogeneous Bronsted acid catalysts are tremendously important in industry,
      particularly in catalytic cracking processes. Here we show that these Bronsted
      acid sites can be directly observed at natural abundance by 17 O DNP surface
      enhanced NMR spectroscopy (SENS). We additionally show that the O-H bond length
      in these catalysts can be measured with sub-picometer precision, to enable a
      direct structural gauge of the lability of protons in a given material, which is
      correlated with the pH of the zero point of charge of the material. Experiments
      performed on materials impregnated with pyridine also allow for the direct
      detection of intermolecular hydrogen bonding interactions through the lengthening
      of O-H bonds.

PMID- 28499072
TI  - Sequencing of bulks of segregants allows dissection of genetic control of amylose
      content in rice.
AB  - Amylose content (AC) is a key quality trait in rice. A cross between Oryza
      glaberrima (African rice) and Oryza sativa (Asian rice) segregating for AC was
      analysed by sequencing bulks of individuals with high and low AC. SNP associated
      with the granule bound starch synthase (GBSS1) locus on chromosome 6 were
      polymorphic between the bulks. In particular, a G/A SNP that would result in an
      Asp to Asn mutation was identified. This amino acid substitution may be
      responsible for differences in GBSS activity as it is adjacent to a disulphide
      linkage conserved in all grass GBSS proteins. Other polymorphisms in genomic
      regions closely surrounding this variation may be the result of linkage drag. In
      addition to the variant in the starch biosynthesis gene, SNP on chromosomes 1 and
      11 linked to AC was also identified. SNP was found in the genes encoding the NAC
      and CCAAT-HAP5 transcription factors that have previously been linked to starch
      biosynthesis. This study has demonstrated that the approach of sequencing bulks
      was able to identify genes on different chromosomes associated with this complex
      trait.

PMID- 28499073
TI  - Arabidopsis ZED1-related kinases mediate the temperature-sensitive intersection
      of immune response and growth homeostasis.
AB  - Activation of the immune response in plants antagonizes growth and development in
      the absence of pathogens, and such an autoimmune phenotype is often suppressed by
      the elevation of ambient temperature. However, molecular regulation of the
      ambient temperature-sensitive intersection of immune response and growth is
      largely elusive. A genetic screen identified an Arabidopsis mutant, zed1-D, by
      its high temperature-dependent growth retardation. A combination of molecular,
      cytological and genetic approaches was used to investigate the molecular basis
      behind the temperature-sensitive growth and immune response in zed1-D. A dominant
      mutation in HOPZ-ETI-DEFICIENT 1 (ZED1) is responsible for a high temperature
      dependent autoimmunity and growth retardation in zed1-D. The autoimmune phenotype
      in zed1-D is dependent on the HOPZ-ACTIVATED RESISTANCE 1 (ZAR1). ZED1 and some
      ZED1-related kinases (ZRKs) are induced by elevated temperature and function
      cooperatively to suppress the immune response by modulating the transcription of
      SUPPRESSOR OF NPR1-1 CONSTITUTIVE 1 (SNC1) in the absence of pathogens. Our data
      reveal a previously unidentified role of ZRKs in the ambient temperature
      sensitive immune response in the absence of pathogens, and thus reveals a
      possible molecular mechanism underlying the temperature-mediated intersection of
      immune response and growth in plants.

PMID- 28499074
TI  - Drug development and registration: Challenges and opportunities in ovarian
      cancer.

PMID- 28499075
TI  - Regulatory considerations on endpoints in ovarian cancer drug development.
AB  - Ovarian cancer remains a disease entity that is responsible for considerable
      morbidity and mortality among women worldwide. Modern drug research pipelines and
      accelerated drug development timelines applied to other disease entities have
      begun to make an impact on treatment options for patients with advanced ovarian
      cancer, as exemplified by the recent accelerated approval of 2 agents for this
      disease as the forerunners of a growing number of registrational trials.
      Regulatory flexibility for this serious and life-threatening condition spurs the
      consideration of intermediate endpoints for regulatory trial design, including
      potential applications in the development of newer therapeutic classes such as
      targeted therapies and immunotherapies for patients with advanced ovarian cancer.
      Cancer 2017;123:2604-8. (c) 2017 American Cancer Society.

PMID- 28499077
TI  - Unconventional Behavior of Friction at the Nanoscale beyond Amontons' Law.
AB  - By means of a many-body van der Waals (vdW)-corrected density functional theory
      approach, the atomic-scale friction of a prototypical tip-substrate system
      consisting of an Si tip and a graphene substrate is studied. In a loading-sliding
      process, the tip-substrate distance is found to be essential for nanofrictional
      behavior, through determining the competition between vdW contributions and
      electronic contributions. As the tip approaches the substrate, this competition
      results in a smooth transition of normal forces from attraction to repulsion, and
      the friction coefficient in turn undergoes a sign change from negative to
      positive with possible giant magnitude and strong anisotropy. The loading-sliding
      process does not introduce any chemical modification of the underlying system.
      These findings reveal the boundary of validity of Amontons' law, unify negative
      and giant friction coefficients, rationalize the experimentally observed
      anisotropy of nanofriction, and are universal when vdW interactions are crucial,
      all of which are helpful to establish a comprehensive picture of nanofriction.

PMID- 28499076
TI  - Single Cell Analysis Linking Ribosomal (r)DNA and rRNA Copy Numbers to Cell Size
      and Growth Rate Provides Insights into Molecular Protistan Ecology.
AB  - Ribosomal (r)RNA and rDNA have been golden molecular markers in microbial
      ecology. However, it remains poorly understood how ribotype copy number (CN)
      based characteristics are linked with diversity, abundance, and activity of
      protist populations and communities observed at organismal levels. Here, we
      applied a single-cell approach to quantify ribotype CNs in two ciliate species
      reared at different temperatures. We found that in actively growing cells, the
      per-cell rDNA and rRNA CNs scaled with cell volume (CV) to 0.44 and 0.58 powers,
      respectively. The modeled rDNA and rRNA concentrations thus appear to be much
      higher in smaller than in larger cells. The observed rRNA:rDNA ratio scaled with
      CV0.14 . The maximum growth rate could be well predicted by a combination of per
      cell ribotype CN and temperature. Our empirical data and modeling on single-cell
      ribotype scaling are in agreement with both the metabolic theory of ecology and
      the growth rate hypothesis, providing a quantitative framework for linking
      cellular rDNA and rRNA CNs with body size, growth (activity), and biomass
      stoichiometry. This study also demonstrates that the expression rate of rRNA
      genes is constrained by cell size, and favors biomass rather than abundance-based
      interpretation of quantitative ribotype data in population and community ecology
      of protists.

PMID- 28499078
TI  - Genomewide analysis of the lateral organ boundaries domain gene family in
      Eucalyptus grandis reveals members that differentially impact secondary growth.
AB  - Lateral Organ Boundaries Domain (LBD) proteins are plant-specific transcription
      factors playing crucial roles in growth and development. However, the function of
      LBD proteins in Eucalyptus grandis remains largely unexplored. In this study, LBD
      genes in E. grandis were identified and characterized using bioinformatics
      approaches. Gene expression patterns in various tissues and the transcriptional
      responses of EgLBDs to exogenous hormones were determined by qRT-PCR. Functions
      of the selected EgLBDs were studied by ectopically overexpressing in a hybrid
      poplar (Populus alba * Populus glandulosa). Expression levels of genes in the
      transgenic plants were investigated by RNA-seq. Our results showed that there
      were forty-six EgLBD members in the E. grandis genome and three EgLBDs displayed
      xylem- (EgLBD29) or phloem-preferential expression (EgLBD22 and EgLBD37).
      Confocal microscopy indicated that EgLBD22, EgLBD29 and EgLBD37 were localized to
      the nucleus. Furthermore, we found that EgLBD22, EgLBD29 and EgLBD37 were
      responsive to the treatments of indol-3-acetic acid and gibberellic acid. More
      importantly, we demonstrated EgLBDs exerted different influences on secondary
      growth. Namely, 35S::EgLBD37 led to significantly increased secondary xylem,
      35S::EgLBD29 led to greatly increased phloem fibre production, and 35S::EgLBD22
      showed no obvious effects. We revealed that key genes related to gibberellin,
      ethylene and auxin signalling pathway as well as cell expansion were
      significantly up- or down-regulated in transgenic plants. Our new findings
      suggest that LBD genes in E. grandis play important roles in secondary growth.
      This provides new mechanisms to increase wood or fibre production.

PMID- 28499080
TI  - Efficient Electrocatalytic Reduction of CO2 by Nitrogen-Doped Nanoporous
      Carbon/Carbon Nanotube Membranes: A Step Towards the Electrochemical CO2
      Refinery.
AB  - Herein we introduce a straightforward, low cost, scalable, and technologically
      relevant method to manufacture an all-carbon, electroactive, nitrogen-doped
      nanoporous-carbon/carbon-nanotube composite membrane, dubbed "HNCM/CNT". The
      membrane is demonstrated to function as a binder-free, high-performance gas
      diffusion electrode for the electrocatalytic reduction of CO2 to formate. The
      Faradaic efficiency (FE) for the production of formate is 81 %. Furthermore, the
      robust structural and electrochemical properties of the membrane endow it with
      excellent long-term stability.

PMID- 28499079
TI  - Development of an atrophic acne scar risk assessment tool.
AB  - BACKGROUND: Acne is a chronic dermatological disease predominantly afflicting
      young adults and is often associated with the development of scars. Acne scarring
      is usually avoidable when acne is managed early and effectively. However, acne
      patients often fail to seek early treatment. New and innovative tools to raise
      awareness are needed. OBJECTIVE: This study presents the development and
      assessment of a tool aiming to assess the risk of atrophic acne scars. METHODS: A
      systematic literature review of clinical risk factors for acne scars, a Delphi
      like survey of dermatological experts in acne and secondary data analysis, were
      conducted to produce an evidence-based risk assessment tool. The tool was
      assessed both with a sample of young adults with and without scars and was
      assessed via a database cross-validation. RESULTS: A self-administered tool for
      risk assessment of developing atrophic acne scars in young adults was developed.
      It is a readily comprehensible and practical tool for population education and
      for use in medical practices. It comprises of four risk factors: worst ever
      severity of acne, duration of acne, family history of atrophic acne scars and
      lesion manipulation behaviours. It provides a dichotomous outcome: lower vs.
      higher risk of developing scars, thereby categorizing nearly two-thirds of the
      population correctly, with sensitivity of 82% and specificity of 43%. CONCLUSION:
      The present tool was developed as a response to current challenges in acne scar
      prevention. A potential benefit is to encourage those at risk to self-identify
      and to seek active intervention of their acne. In clinical practice, we expect
      this tool may help clinicians identify patients at risk of atrophic acne scarring
      and underscore their requirement for rapid and effective acne treatment.

PMID- 28499081
TI  - Negative correlation between serum uric acid and kidney URAT1 mRNA expression
      caused by resveratrol in rats.
AB  - SCOPE: This study established a hyperuricemic rat model to elucidate the effect
      of resveratrol on the transport of UA in the kidney. METHODS AND RESULTS:
      Hyperuricemia was induced in rats through daily oral gavage of a potassium
      oxonate and UA mixture over 3 weeks. Our results revealed that resveratrol
      significantly reduced the serum UA levels but not creatinine, c-creative protein,
      alanine aminotransferase, or aspartate aminotransferase levels in these rats.
      Furthermore, renal URAT1 and OAT1 mRNA expression were significantly higher in
      the rats treated with allopurinol than in those with no treatment. Therefore,
      allopurinol not only inhibited UA production but also mediated renal URAT1 and
      OAT1 expression. The correlation analysis revealed that UA levels correlated
      negatively with renal IL-6 mRNA expression in rats treated with allopurinol.
      Moreover, URAT1 showed strong immunoreactivity in the distal convoluted tubule of
      rats treated with allopurinol or resveratrol and in hyperuricemic treated with
      allopurinol. Finally, in the rats treated with resveratrol, UA levels correlated
      negatively with renal URAT1 mRNA expression; thus, resveratrol reduced URAT1 mRNA
      expression under high UA levels, thereby reducing UA reabsorption in renal cells.
      CONCLUSION: Resveratrol contributes to URAT1 expression, which is potentially
      useful in therapeutic strategies aimed at treating hyperuricemia.

PMID- 28499083
TI  - Brief Psychotic Episode Caused by Advair Diskus in a Pediatric Patient.

PMID- 28499082
TI  - Exacerbation of liver steatosis following exposure to famine and overnutrition.
AB  - SCOPE: People suffering from famine in early life and overnutrition in adulthood
      may have an increased risk for liver steatosis. We aimed to investigate the
      effects and mechanisms of early nutrition restriction and overnutrition on de
      novo lipogenesis in the liver. METHODS AND RESULTS: Three-wk-old male rats were
      food restricted for 4 wk and refed a high-fat or normal fat diet individually in
      metabolic cages for 9 wk. Weight-matched groups were also set up. Fatty acid
      synthetase expression was measured to estimate de novo lipogenesis in the liver.
      Parameters of glucose and lipid metabolism were measured with isotope assays. All
      four groups had comparable body weights. However, the famine high-fat diet group
      had the highest degree of liver steatosis, the greatest body fat ratio, and
      insulin resistance. Lipid accumulation, fatty acid synthetase expression, and
      gluconeogenesis in the liver were significantly higher in the famine and high-fat
      diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle
      glucose uptake. CONCLUSION: Under famine and high-fat refeeding stress, rats were
      extremely susceptible to developing hepatic steatosis. This is presumably a
      consequence of upregulation of de novo lipogenesis and enhanced glucose flux from
      muscle to de novo lipogenesis in the liver.

PMID- 28499084
TI  - Psychological Assessment of Emirati Patients Pursuing Bariatric Surgery for
      Obesity.
AB  - Background: Obesity is currently a rapidly growing global problem of epidemic
      proportions and is especially prevalent in economically developed countries such
      as the United Arab Emirates. Obese individuals are increasingly considering
      bariatric surgery as their preferred means of choice for the reduction of excess
      body fat. This study explored the psychological characteristics that may
      potentially complicate the surgical management of obesity. Methods: This was a
      cross-sectional study of Emirati patients attending a bariatric clinic at Tawam
      Hospital, Al Ain, United Arab Emirates, between December 2010 and February 2012.
      Participants were assessed using standard clinical psychiatric interviews. Also
      used were screening instruments such as the Hospital Anxiety and Depression
      Scale, Sheehan Disability Scale (SDS), Body Image Quality of Life Inventory
      (BIQLI), and Multidimensional Body-Self Relations Questionnaire-Appearance Scale
      (MBSRQ-AS). Results: A total of 105 patients, 70% of whom were female,
      participated in this study. Participants were found to have frequencies of
      anxiety and depressive symptoms at levels of 24% and 13%, respectively.
      Participants also reported perceived functional disabilities in the following:
      work/school (27%), social life (36%), family/home (35%), and religious duties
      (39%). A total of 13 participants (12%) had BIQLI scores showing slight-to
      moderate effects on their quality of life. The mean MBSRQ-AS subscale on self
      classified weight was higher than the reported norms. Anxiety and depressive
      symptoms positively correlated with functional impairment (SDS) and negatively
      correlated with quality of life (BIQLI) (P = .000). MBSRQ-AS subscales
      significantly correlated with depression, functional impairment, and quality of
      life (P <= .035). Conclusions: Anxiety, depression, perceived functional
      disability, impairment in quality of life, and disturbance of self-image were
      found to be common among participants in the study pursuing bariatric surgery for
      obesity. Recognition, assessment, and treatment of these symptoms are expected to
      be conducive to positive outcomes of bariatric surgery.

PMID- 28499085
TI  - Simultaneous Oxidation and Sequestration of As(III) from Water by Using Redox
      Polymer-Based Fe(III) Oxide Nanocomposite.
AB  - Water decontamination from As(III) is an urgent but still challenging task.
      Herein, we fabricated a bifunctional nanocomposite HFO@PS-Cl for highly efficient
      removal of As(III), with active chlorine covalently binding spherical polystyrene
      host for in situ oxidation of As(III) to As(V), and Fe(III) hydroxide (HFO)
      nanoparticles (NPs) embedded inside for specific As(V) removal. HFO@PS-Cl could
      work effectively in a wide pH range (5-9), and other substances like sulfate,
      chloride, bicarbonate, silicate, and humic acid exert insignificant effect on
      As(III) removal. As(III) sequestration is realized via two pathways, that is,
      oxidation to As(V) by the active chlorine followed by specific As(V) adsorption
      onto HFO NPs, and As(III) adsorption onto HFO NPs followed by oxidation to As(V).
      The exhausted HFO@PS-Cl could be refreshed for cyclic runs with insignificant
      capacity loss by the combined regeneration strategy, that is, alkaline solution
      to rinse the adsorbed As(V) and NaClO solution to renew the host oxidation
      capability. In addition, fixed-bed experiments demonstrated that the HFO@PS-Cl
      column could generate >1760 bed volume (BV) effluent from a synthetic As(III)
      containing groundwater to meet the drinking water standard (<10 MUg As/L),
      whereas other two HFO nanocomposites, HFO@PS-N and HFO@D201 could only generate
      450 and 600 BV effluents under otherwise identical conditions.

PMID- 28499086
TI  - Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity
      Hemagglutinin Binding Protein.
AB  - Influenza is a ubiquitous and recurring infection that results in approximately
      500 000 deaths globally each year. Commercially available rapid diagnostic tests
      are based upon detection of the influenza nucleoprotein, which are limited in
      that they are unable to differentiate by species and require an additional viral
      lysis step. Sample preprocessing can be minimized or eliminated by targeting the
      intact influenza virus, thereby reducing assay complexity and leveraging the
      large number of hemagglutinin proteins on the surface of each virus. Here, we
      report the development of a paper-based influenza assay that targets the
      hemagglutinin protein; the assay employs a combination of antibodies and novel
      computationally designed, recombinant affinity proteins as the capture and
      detection agents. This system leverages the customizability of recombinant
      protein design to target the conserved receptor-binding pocket of the
      hemagglutinin protein and to match the trimeric nature of hemagglutinin for
      improved avidity. Using this assay, we demonstrate the first instance of intact
      influenza virus detection using a combination of antibody and affinity proteins
      within a porous network. The recombinant head region binder based assays yield
      superior analytical sensitivity as compared to the antibody based assay, with
      lower limits of detection of 3.54 * 107 and 1.34 * 107 CEID50/mL for the mixed
      and all binder stacks, respectively. Not only does this work describe the
      development of a novel influenza assay, it also demonstrates the power of
      recombinant affinity proteins for use in rapid diagnostic assays.

PMID- 28499088
TI  - Lewis Acid-Catalyzed Nucleophilic Addition of Indoles to in Situ-Generated 2
      Amidoallyl Cations.
AB  - We report herein the first Lewis acid-catalyzed generation of 2-amidoallyl
      cations through ring-opening of 4-benzylidene-2-oxazolines with Sc(OTf)3. Upon
      nucleophilic addition of indoles, indolylenamides were obtained with yields of 60
      99% and excellent (Z)-selectivity. In addition, the novel strategy was also
      successfully applied to pyrroles and naphthols as pi-nucleophiles. A Bronsted
      acid-catalyzed process using TfOH formed in situ was ruled out by control
      experiments.

PMID- 28499087
TI  - Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K+
      Channels.
AB  - Gating of ion channels is based on structural transitions between open and closed
      states. To uncover the chemical basis of individual gates, we performed a
      comparative experimental and computational analysis between two K+ channels, KcvS
      and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of
      only 82 amino acids, resemble the pore module of all complex K+ channels in terms
      of structure and function. Even though both proteins share about 90% amino acid
      sequence identity, they exhibit different open probabilities with ca. 90% in
      KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular
      dynamics simulations show that the difference in open probability is caused by
      one long closed state in KcvS. This state is structurally created in the
      tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The
      resulting kink in the inner transmembrane domain swings the aromatic rings from
      downstream Phes in the cavity of the channel, which blocks ion flux. The frequent
      occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a
      similar mechanism could also occur in the gating of other ion channels.

PMID- 28499089
TI  - Nanoencapsulation of Aloe vera in Synthetic and Naturally Occurring Polymers by
      Electrohydrodynamic Processing of Interest in Food Technology and Bioactive
      Packaging.
AB  - This work originally reports on the use of electrohydrodynamic processing (EHDP)
      to encapsulate Aloe vera (AV, Aloe barbadensis Miller) using both synthetic
      polymers, i.e., polyvinylpyrrolidone (PVP) and poly(vinyl alcohol) (PVOH), and
      naturally occurring polymers, i.e., barley starch (BS), whey protein concentrate
      (WPC), and maltodextrin. The AV leaf juice was used as the water-based solvent
      for EHDP, and the resultant biopolymer solution properties were evaluated to
      determine their effect on the process. Morphological analysis revealed that, at
      the optimal processing conditions, synthetic polymers mainly produced fiber-like
      structures, while naturally occurring polymers generated capsules. Average sizes
      ranged from 100 nm to above 3 MUm. As a result of their different and optimal
      morphology and, hence, higher AV content, PVP, in the form of nanofibers, and
      WPC, of nanocapsules, were further selected to study the AV stability against
      ultraviolet (UV) light exposure. Fourier transform infrared (FTIR) spectroscopy
      confirmed the successful encapsulation of AV in the biopolymer matrices,
      presenting both encapsulants a high chemical interaction with the bioactive
      components. Ultraviolet-visible (UV-vis) spectroscopy showed that, while PVP
      nanofibers offered a poor effect on the AV degradation during UV light exposure
      (~10% of stability after 5 h), WPC nanobeads delivered excellent protection
      (stability of >95% after 6 h). This was ascribed to positive interactions between
      WPC and the hydrophilic components of AV and the inherent UV-blocking and oxygen
      barrier properties provided by the protein. Therefore, electrospraying of food
      hydrocolloids interestingly appears as a novel potential nanotechnology tool
      toward the formulation of more stable functional foods and nutraceuticals.

PMID- 28499090
TI  - Two-Dimensional Cadmium Chloride Nanosheets in Cadmium Telluride Solar Cells.
AB  - In this study we make use of a liquid nitrogen-based thermomechanical cleavage
      technique and a surface analysis cluster tool to probe in detail the tin
      oxide/emitter interface at the front of completed CdTe solar cells. We show that
      this thermomechanical cleavage occurs within a few angstroms of the SnO2/emitter
      interface. An unexpectedly high concentration of chlorine at this interface,
      ~20%, was determined from a calculation that assumed a uniform chlorine
      distribution. Angle-resolved X-ray photoelectron spectroscopy was used to further
      probe the structure of the chlorine-containing layer, revealing that both sides
      of the cleave location are covered by one-third of a unit cell of pure CdCl2, a
      thickness corresponding to about one Cl-Cd-Cl molecular layer. We interpret this
      result in the context of CdCl2 being a true layered material similar to
      transition-metal dichalcogenides. Exposing cleaved surfaces to water shows that
      this Cl-Cd-Cl trilayer is soluble, raising questions pertinent to cell
      reliability. Our work provides new and unanticipated details about the structure
      and chemistry of front surface interfaces and should prove important to improving
      materials, processes, and reliability of next-generation CdTe-based solar cells.

PMID- 28499091
TI  - Dynamics of a Water Droplet over a Sessile Oil Droplet: Compound Droplets
      Satisfying a Neumann Condition.
AB  - We report the dynamics of compound droplets with a denser liquid (water) droplet
      over a less dense sessile droplet (mineral oil) that satisfies the Neumann
      condition. For a fixed size of an oil droplet, depending on the size of the water
      droplet, either it attains the axisymmetric position or tends to migrate toward
      the edge of the oil droplet. For a water droplet-to-oil droplet at volume ratio
      Vw/Vo >= 0.05, stable axisymmetric configuration is achieved; for Vw/Vo < 0.05,
      migration of water droplet is observed. The stability and migration of water
      droplets of size above and below critical size, respectively, are explained using
      the force balance at the three-phase contact line and film tension. The larger
      and smaller droplets that initially attain the axisymmetric position or some
      radial position, respectively, evaporate continuously and thus migrate toward the
      edge of the oil droplet. The radial location and migration of the water droplets
      of different initial sizes with respect to time are studied. Experiments with
      water droplets on a flat oil-air interface did not show migration, which
      signified the role of the curved oil-air interface for droplet migration.
      Finally, coalescence of water droplets of size above the critical size at the
      axisymmetric position is demonstrated. Our compound droplet studies could be
      beneficial for applications involving droplet transport where contamination due
      to direct contact and pinning of droplets on solid surfaces is of concern.
      Migration and coalescence of water droplets on curved oil-air interfaces could
      open new frontiers in chemical and biological applications including multiphase
      processing and biological interaction of cells and atmospheric chemistry.

PMID- 28499092
TI  - Determining the Conduction Band-Edge Potential of Solar-Cell-Relevant Nb2O5
      Fabricated by Atomic Layer Deposition.
AB  - Often key to boosting photovoltages in photoelectrochemical and related solar
      energy-conversion devices is the preferential slowing of rates of charge
      recombination-especially recombination at semiconductor/solution,
      semiconductor/polymer, or semiconductor/perovskite interfaces. In devices
      featuring TiO2 as the semiconducting component, a common approach to slowing
      recombination is to install an ultrathin metal oxide barrier layer or trap
      passivating layer atop the semiconductor, with the needed layer often being
      formed via atomic layer deposition (ALD). A particularly promising barrier layer
      material is Nb2O5. Its conduction-band-edge potential ECB is low enough that
      charge injection from an adsorbed molecular, polymeric, or solid-state light
      absorber and into the semiconductor can still occur, but high enough that charge
      recombination is inhibited. While a few measurements of ECB have been reported
      for conventionally synthesized, bulk Nb2O5, none have been described for ALD
      fabricated versions. Here, we specifically determine the conduction-band-edge
      energy of ALD-fabricated Nb2O5 relative to that of TiO2. We find that, while the
      value for ALD-Nb2O5 is indeed higher than that for TiO2, the difference is less
      than anticipated based on measurements of conventionally synthesized Nb2O5 and is
      dependent on the thermal history of the material. The implications of the
      findings for optimization of competing interfacial rate processes, and therefore
      photovoltages, are briefly discussed.

PMID- 28499093
TI  - The Segond Fracture Is an Avulsion of the Anterolateral Complex.
AB  - BACKGROUND: The Segond fracture was classically described as an avulsion fracture
      of the anterolateral capsule of the knee. Recently, some authors have attributed
      its pathogenesis to the "anterolateral ligament" (ALL). Biomechanical studies
      that have attempted to reproduce this fracture in vitro have reported conflicting
      findings. PURPOSE: To determine the anatomic characteristics of the Segond
      fracture on plain radiographs and magnetic resonance imaging (MRI), to compare
      this location with the location of the ALL described in prior radiographic and
      anatomic publications, and to determine the fracture's attachments to the soft
      tissue anterolateral structures of the knee. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: A total of 36 anterior cruciate ligament-injured patients
      with Segond fractures (33 male, 3 female; mean age, 23.2 +/- 8.4 years) were
      enrolled. MRI scans were reviewed to determine the anatomic characteristics of
      the Segond fracture, including the following: proximal-distal (PD) length,
      anterior-posterior (AP) width, medial-lateral (ML) width, PD distance to the
      lateral tibial plateau, AP distance to the Gerdy tubercle (GT), and AP distance
      from the GT to the posterior aspect of the fibular head. The attachment of the
      anterolateral structures to the Segond fragment was then categorized as the
      iliotibial band (ITB) or anterolateral capsule. Interrater reliability of the
      measurements was determined by calculating the Spearman rank correlation
      coefficient. MEDLINE, Web of Science, and the Cochrane Library were searched from
      inception to May 2016 for the following keywords: (1) "Segond fracture," (2)
      "anterolateral ligament," (3) "knee avulsion," (4) "lateral tibia avulsion," and
      (5) "tibial plateau avulsion." All studies describing the anatomic location of
      the Segond fracture and the ALL were included in the systematic review. RESULTS:
      On plain radiographs, the mean distance of the midpoint of the fracture to the
      lateral tibial plateau was 4.6 +/- 2.2 mm. The avulsed fracture had a mean PD
      length of 9.2 +/- 2.5 mm and a mean ML width of 2.4 +/- 1.4 mm. On MRI, the mean
      distance of the proximal fracture to the tibial plateau was 3.4 +/- 1.6 mm. The
      mean PD length was 8.7 +/- 2.2 mm, while the mean AP width was 11.1 +/- 2.2 mm.
      The mean distance between the GT and the center of the fracture was 26.9 +/- 3.3
      mm, while the mean distance between the GT and the posterior fibular head was
      53.9 +/- 4.4 mm. The mean distance of the midpoint of the fracture to the tibial
      plateau was 7.8 +/- 2.7 mm, while the center of the fracture was 49.9% of the
      distance between the GT and the posterior aspect of the fibular head. Analysis of
      soft tissue structures attached to the fragment revealed that the ITB attached in
      34 of 36 patients and the capsule attached in 34 of 36 patients. One patient had
      only the capsule attached, another had only the ITB attached, and the last showed
      neither clearly attached. A literature review of 20 included studies revealed no
      difference between the previously described Segond fracture location and the
      tibial insertion of the ALL. CONCLUSION: The results of this study confirmed that
      while the Segond fracture occurs at the location of the tibial insertion of the
      ALL, as reported in the literature, MRI was unable to identify any distinct
      ligamentous attachment. MRI analysis revealed that soft tissue attachments to the
      Segond fracture were the posterior fibers of the ITB and the lateral capsule in
      94% of patients.

PMID- 28499094
TI  - The Epidemiology and Effect of Sliding Injuries in Major and Minor League
      Baseball Players.
AB  - BACKGROUND: Although sliding occurs frequently in professional baseball, little
      is known about the epidemiology and effect of injuries that occur during sliding
      in this population of elite athletes. PURPOSE: To describe the incidence and
      characteristics of sliding injuries, determine their effect in terms of time out
      of play, and identify common injury patterns that may represent appropriate
      targets for injury prevention programs in the future. STUDY DESIGN: Descriptive
      epidemiologic study. METHODS: All offensive sliding injuries occurring in Major
      League Baseball (MLB) and Minor League Baseball (MLB) that resulted in time out
      of play during a span of 5 seasons (2011-2015) were identified. In addition to
      player demographics, data extracted included time out of play, location on field
      where injury occurred, level of play, treatment (surgical vs nonsurgical),
      direction of slide (head vs feet first), body region injured, and diagnosis.
      Descriptive statistics were used to describe the distribution of these injuries,
      and injury rates were calculated per slide. RESULTS: From 2011 to 2015, 1633
      injuries occurred as a result of a slide. The total number of days missed per
      season was 4263. Surgical intervention was required for 134 (8.2%) injuries, and
      the mean days missed was 66.5 for players treated surgically and 12.3 days for
      players treated nonoperatively ( P < .001). MLB players were more likely than
      MiLB players to require surgical intervention (12.3% vs 7.5%, P = .019). Injuries
      to the hands/fingers represented 25.3% of all injuries and 31.3% of those
      requiring surgery. Although the majority of injuries occurred at second base
      (57%), the per-slide injury rate was similar across all bases ( P = .991). The
      estimated overall frequency of injury in MLB was once per every 336 slides, and
      the rate of injury for head- and feet-first slides was 1 in 249 and 413 slides,
      respectively ( P = .119). CONCLUSION: Injuries occurring while sliding in
      professional baseball result in a significant amount of time out of play for
      these elite athletes. Injuries occurring at second base and those occurring to
      the hands and fingers were most prevalent and may be an appropriate target for
      future injury prevention programs.

PMID- 28499095
TI  - TRPM7 Is Involved in Volume Regulation in Salivary Glands.
AB  - Under hypotonic conditions, the regulatory volume decrease (RVD) is essential to
      maintain physiological homeostasis and functions in diverse biological systems.
      Intracellular Ca2+ has been reported as an important mediator of this response,
      but the underlying Ca2+ mechanism responsible for RVD is still controversial.
      Here we investigate the role of Ca2+ in the RVD response using live-cell imaging,
      microspectrofluorimetry, and a patch-clamp technique. A typical RVD was observed
      in submandibular gland acinar cells after swelling in a hypotonic solution,
      whereas intracellular Ca2+ chelation completely inhibited the RVD response. The
      incidence and magnitude of the Ca2+ transient were proportional to the degree of
      hypotonicity of the extracellular medium, and there was a close relationship
      between intracellular Ca2+ concentration and the volumetric changes of the cells.
      Notably, this response was mediated by Ca2+-induced Ca2+ release, which is
      triggered by Ca2+ influx via stretch-activated TRPM7 channels. Furthermore, we
      detected the generation of Cl- currents in the swelling acinar cells upon
      hypotonic stress, and the current profile matched that of the Ca2+-activated Cl-
      currents. A specific inhibitor of Cl- currents also inhibited the RVD response.
      In conclusion, an intracellular Ca2+ increase in response to osmotically induced
      cell swelling plays a critical role in RVD in salivary gland acinar cells.

PMID- 28499096
TI  - Genetic and phenotypic diversity of rhizobia nodulating chickpea (Cicer arietinum
      L.) in soils from southern and central Ethiopia.
AB  - Forty-two chickpea-nodulating rhizobia were isolated from soil samples collected
      from diverse agro-ecological locations of Ethiopia and were characterized on the
      basis of 76 phenotypic traits. Furthermore, 18 representative strains were
      selected and characterized using multilocus sequence analyses of core and
      symbiotic gene loci. Numerical analysis of the phenotypic characteristics grouped
      the 42 strains into 4 distinct clusters. The analysis of the 16S rRNA gene of the
      18 strains showed that they belong to the Mesorhizobium genus. On the basis of
      the phylogenetic tree constructed from the combined genes sequences (recA, atpD,
      glnII, and gyrB), the test strains were distributed into 4 genospecies
      (designated as genospecies I-IV). Genospecies I, II, and III could be classified
      with Mesorhizobium ciceri, Mesorhizobium abyssinicae, and Mesorhizobium shonense,
      respectively, while genospecies IV might represent an unnamed Mesorhizobium
      genospecies. Phylogenetic reconstruction based on the symbiosis-related (nifH and
      nodA) genes supported a single cluster together with a previously described
      symbiont of chickpea (M. ciceri and Mesorhizobium mediterraneum). Overall, our
      results corroborate earlier findings that Ethiopian soils harbor phylogenetically
      diverse Mesorhizobium species, justifying further explorative studies. The
      observed differences in symbiotic effectiveness indicated the potential to select
      effective strains for use as inoculants and to improve the productivity of
      chickpea in the country.

PMID- 28499098
TI  - Editor's Corner: Does a Little Drinking Make Your Heart Grow Stronger?

PMID- 28499097
TI  - Substantivity of Carbodiimide Inhibition on Dentinal Enzyme Activity over Time.
AB  - The use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC) has recently
      been investigated for its effectiveness in the prevention of collagen degradation
      over time and the improvement of resin-dentin bond durability. The objective of
      the present study was to evaluate the effects of a 0.3 M EDC-containing
      conditioner on endogenous enzymatic activities within the hybrid layer (HL)
      created by a self-etch or an etch-and-rinse adhesive after 1 y. The activity
      within the HL was examined using in situ zymography and confocal laser scanning
      microscopy after 24 h or 1-y storage in artificial saliva. Dentin specimens were
      bonded with Clearfil SE Bond (CSE) or XP Bond (XPB). For CSE, the self-etching
      primer was applied and treated with 0.3 M EDC for 1 min, and then the bonding
      agent was applied. For XPB, dentin was etched and treated with 0.3 M EDC for 1
      min and then bonded with the primer-bonding agent. Control specimens were
      prepared without EDC treatment. Slices containing the adhesive-dentin interface
      were covered with fluorescein-conjugated gelatin and observed with a multiphoton
      confocal microscope. Fluorescence intensity emitted by hydrolyzed fluorescein
      conjugated gelatin was quantified, and the amount of gelatinolytic activity was
      represented by the percentage of green fluorescence emitted within the HL. After
      24 h of storage, enzymatic activity was detected by in situ zymography within the
      HLs of both tested adhesives, with XPB higher than CSE ( P < 0.05). Almost no
      fluorescence signal was detected when specimens were pretreated with EDC compared
      to controls ( P < 0.05). After 1 y of storage, enzymatic activities significantly
      increased for all groups (excluding XPB control) compared to 24-h storage ( P <
      0.05), with EDC pretreated specimens exhibiting significantly lower activity than
      controls ( P < 0.05). The present study showed, for the first time, that the use
      of EDC for both the self-etch and the etch-and-rinse approaches results in the
      reduction but not complete inhibition of matrix-bound collagenolytic enzyme
      activities over time in the HL.

PMID- 28499099
TI  - Evidence for Sex Convergence in Prevalence of Cannabis Use: A Systematic Review
      and Meta-Regression.
AB  - OBJECTIVE: Generally, cannabis use has been more prevalent in men than in women.
      However, emerging evidence suggests that the prevalence of cannabis use is
      converging among males and females from recent cohorts. This study aimed to
      systematically summarize published literature on birth cohort changes in male-to
      female ratios in prevalence of cannabis use. METHOD: Twenty-two studies with a
      median sample size of 85,052 were identified for inclusion. Data were collected
      between 1979 and 2010, representing birth cohorts from 1936 to 1999. For
      quantitative synthesis, male-to-female ratios in prevalence of any cannabis use
      were calculated for all 5-year birth cohorts available, generating 348 separate
      ratios among birth cohorts from 1941 to 1995 in 30 countries. Random-effects meta
      analyses generated pooled sex ratios, stratified by 5-year birth cohorts.
      RESULTS: Of the 22 included studies, 10 reported some evidence of sex convergence
      in cannabis use among more recent cohorts. Quantitative synthesis found that the
      ratio of cannabis use prevalence in males and females decreased significantly
      from 2.0 among cohorts born in 1941 to 1.3 among those born in 1995. CONCLUSIONS:
      Findings support the narrowing sex gap in the prevalence of cannabis use. Results
      are concordant with a broader literature demonstrating sex convergence in
      prevalence of other substance use, particularly alcohol use and related harms.
      Both young women and men should be the target of prevention and early
      intervention efforts. Future research in more diverse global settings, especially
      in low- and middle-income countries, would enhance the international scope of the
      findings.

PMID- 28499101
TI  - Targeting Stress Neuroadaptations for Addiction Treatment: A Commentary on Kaye
      et al. (2017).

PMID- 28499102
TI  - Alcohol Consumption and Mortality From Coronary Heart Disease: An Updated Meta
      Analysis of Cohort Studies.
AB  - OBJECTIVE: Previous meta-analyses estimate that low-volume alcohol consumption
      protects against coronary heart disease (CHD). Potential errors in studies
      include systematic misclassification of drinkers as abstainers, inadequate
      measurement, and selection bias across the life course. METHOD: Prospective
      studies of alcohol consumption and CHD mortality were identified in scholarly
      databases and reference lists. Studies were coded for potential abstainer biases
      and other study characteristics. The alcohol-CHD risk relationship was estimated
      in mixed models with controls for potential biases. Stratified analyses were
      performed based on variables identified as potential effect modifiers. RESULTS:
      Fully adjusted meta-analysis of all 45 studies found significantly reduced CHD
      mortality for current low-volume drinkers (relative risk [RR] = 0.80, 95% CI
      [0.69, 0.93]) and all current drinkers (RR = 0.88, 95% CI [0.78, 0.99]). There
      was evidence of effect modification by cohort age, gender, ethnicity, and heart
      health at baseline. In stratified analyses, low-volume consumption was not
      significantly protective for cohorts ages 55 years or younger at baseline (RR =
      0.95, 95% CI [0.75, 1.21]), for studies controlling for heart health (RR = 0.87,
      95% CI [0.71, 1.06]), or for higher quality studies (RR = 0.86, 95% CI [0.68,
      1.09]). In studies in which the mean age was 55 years or younger at baseline,
      there were significantly increased RRs for both former (RR = 1.45, 95% CI [1.08,
      1.95]) and occasional drinkers (RR = 1.44, 95% CI [1.09, 1.89]) compared with
      abstainers. CONCLUSIONS: Pooled analysis of all identified studies suggested an
      association between alcohol use and reduced CHD risk. However, this association
      was not observed in studies of those age 55 years or younger at baseline, in
      higher quality studies, or in studies that controlled for heart health. The
      appearance of cardio-protection among older people may reflect systematic
      selection biases that accumulate over the life course.

PMID- 28499100
TI  - Probing for Neuroadaptations to Unpredictable Stressors in Addiction:
      Translational Methods and Emerging Evidence.
AB  - Stressors clearly contribute to addiction etiology and relapse in humans, but our
      understanding of specific mechanisms remains limited. Rodent models of addiction
      offer the power, flexibility, and precision necessary to delineate the causal
      role and specific mechanisms through which stressors influence alcohol and other
      drug use. This review describes a program of research using startle potentiation
      to unpredictable stressors that is well positioned to translate between animal
      models and clinical research with humans on stress neuroadaptations in addiction.
      This research rests on a solid foundation provided by three separate pillars of
      evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in
      addiction, (b) rodent affective neuroscience on startle potentiation, and (c)
      human addiction and affective science with startle potentiation. Rodent stress
      neuroadaptation models implicate adaptations in corticotropin-releasing factor
      and norepinephrine circuits within the central extended amygdala following
      chronic alcohol and other drug use that mediate anxious behaviors and stress
      induced reinstatement among drug-dependent rodents. Basic affective neuroscience
      indicates that these same neural mechanisms are involved in startle potentiation
      to unpredictable stressors in particular (vs. predictable stressors). We believe
      that synthesis of these evidence bases should focus us on the role of
      unpredictable stressors in addiction etiology and relapse. Startle potentiation
      in unpredictable stressor tasks is proposed to provide an attractive and flexible
      test bed to encourage tight translation and reverse translation between animal
      models and human clinical research on stress neuroadaptations. Experimental
      therapeutics approaches focused on unpredictable stressors hold high promise to
      identify, repurpose, or refine pharmacological and psychosocial interventions for
      addiction.

PMID- 28499103
TI  - No Benefit of Light to Moderate Drinking for Mortality From Coronary Heart
      Disease When Better Comparison Groups and Controls Included: A Commentary on Zhao
      et al. (2017).

PMID- 28499104
TI  - Robustness of the J-Shaped Association of Alcohol With Coronary Heart Disease
      Risk.

PMID- 28499105
TI  - Whether Low Volume Alcohol Use Is Cardio-Protective Is Important for Public
      Health Policy So the Available Evidence Deserves Critical Analysis: The Authors
      Respond.

PMID- 28499106
TI  - Alcohol and Cigarette Use From Ages 23 to 55: Links With Health and Well-Being in
      the Long-Term National Child Development Study.
AB  - OBJECTIVE: Using longitudinal data from the National Child Development Study, an
      ongoing study of a nationally representative British cohort born in 1958 (n =
      9,137; 51% female), we examined how patterns of alcohol and cigarette use from
      young adulthood (age 23) to midlife (age 55) are associated with health and well
      being. METHOD: We first used a nonparametric multilevel latent class
      specification to identify eight unique paths of alcohol and cigarette use from
      ages 23 to 55, and then assessed how these long-term latent paths related to
      overall health, heart problems, chronic illness, and quality of life at midlife.
      RESULTS: Results show that adults who consistently drank within current U.K. low
      risk guidelines (i.e., not exceeding 14 units of alcohol per week) and abstained
      from smoking from young adulthood to midlife reported the best overall health and
      well-being compared with latent paths involving steady, light to moderate
      drinking and both current and prior smoking, increasing drinking and smoking, and
      infrequent drinking/abstention. CONCLUSIONS: British adults who consistently
      drank within new lower risk guidelines and abstained from smoking from young
      adulthood to midlife reported the best overall health and well-being across
      numerous indicators. However, apparent observed health benefits of stable low
      dose alcohol use (vs. abstention) are weakened by the fact that by age 55 almost
      all alcohol "abstainers" in the National Child Development Study sample were
      former drinkers, and that respondents who followed infrequent drinking/abstention
      paths were the mostly likely to report poor health, psychological distress, and
      low educational qualifications in early adulthood.

PMID- 28499107
TI  - Bias in Assessing Effects of Substance Use From Observational Studies: What Do
      Longitudinal Data Tell Us? A Commentary on Staff and Maggs (2017).

PMID- 28499109
TI  - Public Stigma Toward People With Drug Addiction: A Factorial Survey.
AB  - OBJECTIVE: Stigmatizing attitudes toward people with a drug addiction have
      detrimental effects on the lives of these people. However, the factors that
      influence stigma toward people with a drug addiction have not yet been thoroughly
      investigated, compared with the stigma of other mental illnesses. Based on
      attribution theory, our experiment examined to what extent individual and
      contextual characteristics of people with a drug addiction influence stigmatizing
      attitudes toward people with a drug addiction. Moreover, we explored whether
      respondent characteristics indicative of familiarity with addiction decrease
      stigma toward people with a drug addiction. METHOD: We conducted a full factorial
      survey of 2,857 respondents from a German online access panel who were from all
      walks of life. We experimentally varied vignettes (29-design) that featured a
      fictional person with an addiction. Stigmatizing beliefs, such as blame or fear,
      were assessed using the Attribution Questionnaire (AQ-9). RESULTS: Different
      attributes of people with a drug addiction and of the characteristics of their
      addiction modulated stigma in ways that are mostly consistent with attribution
      theory and related research. For example, female gender and younger age of people
      with a drug addiction diminished several stigmatizing attitudes; greater duration
      of addiction and social influence to use drugs increased them. Furthermore,
      characteristics of respondents modulated stigma: women, younger respondents, and
      those with higher education expressed less-stigmatizing responses than others.
      CONCLUSIONS: The stigmatization of people with a drug addiction is influenced by
      several factors, including characteristics of the stigmatized person, the
      addiction, and the person holding stigmatizing attitudes. A better understanding
      of the underlying mechanisms of these effects is needed to develop evidence-based
      antistigma measures.

PMID- 28499108
TI  - Alcohol Outcomes by Sexual Orientation and Race/Ethnicity: Few Findings of Higher
      Risk.
AB  - OBJECTIVE: This study sought to confirm a previously identified race by sexual
      orientation interaction and to clarify men's alcohol-related risk by using an
      expanded classification of sexual orientation. METHOD: We collapsed three waves
      of National Alcohol Survey data, restricting the analytic sample to White (n =
      5,689), Black (n = 1,237), and Latino (n = 1,549) men with complete information
      on sexual orientation and alcohol use. Using self-reported sexual identity and
      behavior, respondents were categorized as exclusively heterosexual (referent),
      behaviorally discordant heterosexuals (i.e., heterosexual identity and same-sex
      partners), or gay/bisexually identified men. We used multivariable logistic
      regression to model lifetime alcohol dependence symptoms, lifetime drinking
      related consequences, and past-year hazardous drinking, controlling for age,
      education, employment, and relationship status and accounting for the complex
      survey design. RESULTS: There was no difference in risk of past-year hazardous
      drinking and lifetime drinking-related consequences between heterosexual,
      behaviorally discordant heterosexual, and gay/bisexual men, independent of race/
      ethnicity. Among Black men, behaviorally discordant heterosexuals had three-fold
      higher odds of lifetime alcohol dependence symptoms than exclusively heterosexual
      peers (aOR = 3.30, 95% CI [1.19, 9.18], p = .02). Gay/bisexual Latino men had
      marginally significantly lower odds of lifetime alcohol dependence symptoms (aOR
      = 0.36, 95% CI [0.12, 1.03], p = .06). CONCLUSIONS: There is little support for
      broad statements of greater alcohol risk among gay/bisexual men; however, for
      some subgroups and outcomes the direction and degree of risk depend on race/
      ethnicity. Thus, this study underscores the importance of considering the
      potential interaction of sexual orientation and race/ethnicity, which may
      exacerbate or attenuate.

PMID- 28499110
TI  - The Influence of Paternal Separation, Paternal History of Alcohol Use Disorder
      Risk, and Early Substance Use on Offspring Educational Attainment by Young
      Adulthood.
AB  - OBJECTIVE: This study aimed to determine the associations among paternal alcohol
      problems, separation, and educational attainment in European American and African
      American offspring and whether offspring early alcohol/tobacco/marijuana use
      influenced these associations. METHOD: Families with offspring ages 13-19 years
      at intake were selected from state birth records and screened by telephone to
      determine high-risk or low-risk status (with/without paternal heavy drinking).
      Families of men with two or more driving-under-the-influence offenses were added
      as a very-high-risk group. Data from 340 African American and 288 European
      American offspring who were not enrolled in school at their last interview were
      analyzed. Educational attainment was modeled as less than high school, high
      school only (reference category), and some college or higher. Separation was
      defined as offspring report of not having lived continuously in the same
      household with their biological father from birth to age 14. Analyses were
      stratified by race. RESULTS: In European Americans, neither family risk status
      nor early alcohol/tobacco/marijuana use was associated with educational outcomes.
      However, paternal separation significantly elevated the likelihood of not
      completing high school in all models (relative risk ratios [RRRs] = 6.0-8.1, p
      <.001). For African American offspring, likelihoods of high school noncompletion
      were elevated marginally for paternal separation in only one model, but
      significantly for early marijuana use (RRRs = 2.8-3.2, p < .05). Very-high-risk
      status significantly reduced the likelihood of post-high school education in an
      adjusted model (RRR = 0.4, p < .05). CONCLUSIONS: High school noncompletion was
      significantly associated with paternal separation in European Americans and with
      early marijuana use in African American offspring. In addition, very-high-risk
      status reduced the likelihood of post-high school education in African American
      offspring only, suggesting that research with ethnically diverse samples yields
      important differences when examining outcomes of both separation and substance
      use on offspring education.

PMID- 28499111
TI  - Late-Life Drinking Problems: The Predictive Roles of Drinking Level vs. Drinking
      Pattern.
AB  - OBJECTIVE: Research on late-middle-aged and older adults has focused primarily on
      average level of alcohol consumption, overlooking variability in underlying
      drinking patterns. The purpose of the present study was to examine the
      independent contributions of an episodic heavy pattern of drinking versus a high
      average level of drinking as prospective predictors of drinking problems. METHOD:
      The sample comprised 1,107 adults ages 55-65 years at baseline. Alcohol
      consumption was assessed at baseline, and drinking problems were indexed across
      20 years. We used prospective negative binomial regression analyses controlling
      for baseline drinking problems, as well as for demographic and health factors, to
      predict the number of drinking problems at each of four follow-up waves (1, 4,
      10, and 20 years). RESULTS: Across waves where the effects were significant, a
      high average level of drinking (coefficients of 1.56, 95% CI [1.24, 1.95]; 1.48,
      95% CI [1.11, 1.98]; and 1.85, 95% CI [1.23, 2.79] at 1, 10, and 20 years) and an
      episodic heavy pattern of drinking (coefficients of 1.61, 95% CI [1.30, 1.99];
      1.61, 95% CI [1.28, 2.03]; and 1.43, 95% CI [1.08, 1.90] at 1, 4, and 10 years)
      each independently increased the number of drinking problems by more than 50%.
      CONCLUSIONS: Information based only on average consumption underestimates the
      risk of drinking problems among older adults. Both a high average level of
      drinking and an episodic heavy pattern of drinking pose prospective risks of
      later drinking problems among older adults.

PMID- 28499113
TI  - Social and Individual-Level Predictors of Alcohol Use Initiation and Escalation:
      Replicating and Extending Tests of Differential Effects.
AB  - OBJECTIVE: Although alcohol use is considered a developmental phenomenon, there
      is a relative dearth of studies disaggregating predictors of alcohol use
      initiation versus early escalation of drinking. One perspective that has emerged
      is that social levels of influence may be relevant for the initiation of
      drinking, whereas individual levels of influence may be relevant for the early
      escalation in level of drinking among initiators, which we refer to as the
      specificity hypothesis. METHOD: A sample of alcohol-naive youth (n = 944; mean
      age = 12.16 years, SD = 0.96) was prospectively assessed for 3 years, spanning
      six waves of data collection. RESULTS: Both social (parental conflict, perceived
      prevalence of peer drinking) and individual-level (higher sensation seeking)
      variables uniquely predicted increases in the likelihood of alcohol initiation.
      Likewise, both social (perceived descriptive norms of peer drinking) and
      individual-level (lower school grades, higher sensation seeking) variables
      uniquely predicted escalation in level of drinking among initiators (although
      only marginally for sensation seeking). CONCLUSIONS: Overall, there was little
      support for the specificity hypothesis. Our findings suggest that to assume that
      social and individual-level processes differentially predict drinking outcomes
      may be a false dichotomy. Theoretical work may benefit from drawing from
      developmental models emphasizing the interplay between individual and
      environmental factors in the prediction of the early development of drinking. The
      emergence of drinking behaviors is likely to result from a developmental cascade
      of interacting variables that make the ontogeny of drinking unlikely to emerge
      from a single class of variables.

PMID- 28499112
TI  - Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A
      Longitudinal Study.
AB  - OBJECTIVE: Alcohol use problems are common during adolescence and can predict
      serious negative outcomes in adulthood, including substance dependence and
      psychopathology. The current study examines the notion that alcohol use problems
      are driven by polygenic influences and that genetic influences may indirectly
      affect alcohol use problems through multiple pathways of risk, including
      variations in personality. METHOD: We used a genome-wide approach to examine
      associations between genetic risk for alcohol use problems, personality
      dimensions, and adolescent alcohol use problems in two separate longitudinal
      population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon
      Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035
      young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk
      scores (PRS) were calculated for ALSPAC using genome-wide association results (on
      alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple
      mediator model was tested to examine whether the association between PRS and
      alcohol use problems assessed at age 16 could be explained by variations in
      personality dimensions assessed at age 13, including sensation seeking and
      negative emotionality. RESULTS: PRS were marginally predictive of age 16 alcohol
      use problems; this association was partially mediated by sensation seeking.
      Polygenic variation underlying risk for alcohol use problems may directly
      influence the effects of sensation seeking, which in turn influence the
      development of alcohol use problems in later adolescence. CONCLUSIONS: These
      findings contribute to the increasing evidence regarding the salience of
      sensation seeking during early adolescence as a potential constituent in the risk
      pathway underlying the development of alcohol use problems.

PMID- 28499114
TI  - Fathers' Alcohol and Cannabis Use Disorder and Early Onset of Drug Use by Their
      Children.
AB  - OBJECTIVE: The unique influence of fathers' alcohol and cannabis use disorder on
      children's onset of use of these same substances has been rarely studied. A clear
      understanding of family history in this context is important for the development
      of family-based prevention initiatives aimed at delaying the onset of substance
      use among children. METHOD: Prospective, longitudinal, and intergenerational data
      on 274 father-child dyads were used. Logistic regression models were estimated to
      assess the association between fathers' lifetime incidence of an alcohol and
      cannabis use disorder and children's onset of use of these same substances at or
      before age 15. RESULTS: The children of fathers who met the criteria for a
      lifetime cannabis use disorder were more likely to initiate use of alcohol (odds
      ratio = 6.71, 95% CI [1.92, 23.52]) and cannabis (odds ratio = 8.13, 95% CI
      [2.07, 31.95]) by age 15, when background covariates and presence of a lifetime
      alcohol use disorder were controlled for. No unique effect of fathers' alcohol
      use disorder on children's onset of alcohol and cannabis use was observed.
      CONCLUSIONS: Fathers' lifetime cannabis use disorder had a unique and robust
      association with children's uptake of alcohol and cannabis by age 15. Future
      research is needed to identify the mediating mechanisms that link fathers'
      disorder with children's early onset.

PMID- 28499115
TI  - A Comparison of Long- vs. Short-Term Recall of Substance Use and HIV Risk
      Behaviors.
AB  - OBJECTIVE: The Timeline Follow-back (TLFB) questionnaire has become a pre-eminent
      tool in substance use and human immunodeficiency virus (HIV) risk research,
      allowing researchers to assess fine-grained changes in risk behavior over long
      periods. However, data on accuracy of recall over long (12-month) periods are
      sparse, especially combined data on HIV risk and substance use from post
      treatment samples. Studies on the development of substance use and HIV risk stand
      to benefit from data on the accurate recall of such behavior over longer
      retroactive spans of time. METHOD: The present study offers data on the test
      retest reliability of current TLFB assessment versus 6- and 12-month delayed TLFB
      assessment, using a post-treatment sample (n = 50). RESULTS: Long-term
      reliability of TLFB data on HIV risk was predominantly good to excellent, with 13
      of 20 assessed variables in that range. TLFB data on substance use was similar,
      with 22 of 26 variables resulting in good/excellent reliability. CONCLUSIONS: Our
      findings support the notion that, notable exceptions aside, the TLFB may be
      effectively used to assess retroactive HIV risk and substance use in periods of
      12 months.

PMID- 28499116
TI  - Postgraduate Alcohol and Other Drug Practitioner Training in New Zealand:
      Significant Influences.
AB  - OBJECTIVE: The purpose of this article is to present a case study of the
      evolution of postgraduate-level training programs for alcohol and other drug
      (AOD) practitioners provided by two universities in New Zealand. METHOD: The case
      study compiles details on relevant treatment contexts and systems in New Zealand
      and key milestones and significant developments in postgraduate AOD practitioner
      programs in two locations over a 30-year period. The details were compiled by the
      authors, all of whom were closely involved with the development of the training
      programs. RESULTS: The key ingredients for success that were identified included
      a focus on specialized learning overlaying generic undergraduate professional
      training; a core commitment to practice oriented teaching; investment in the
      training by government bodies; and the parallel emergence of professional bodies,
      registration systems, and collaborative relationships across agencies. In a small
      country, the two programs have enabled 345 students to obtain specialist
      postgraduate qualifications in AOD practice over a 10-year period. CONCLUSIONS:
      Little could have been achieved without ongoing cooperation between education
      providers, government agencies, and AOD services. This history may be of interest
      to those in other locations attempting to establish nation- or statewide
      approaches to AOD practitioner training.

PMID- 28499117
TI  - Conclusion Overreach in Alcohol and Pregnancy Article: The Authors Reply.

PMID- 28499118
TI  - Ethanol Concentration of Traditional Alcoholic Beverages in Northern Tanzania.

PMID- 28499119
TI  - Identification of emotions in mixed disgusted-happy faces as a function of
      depressive symptom severity.
AB  - BACKGROUND AND OBJECTIVES: Interpersonal difficulties are common in depression,
      but their underlying mechanisms are not yet fully understood. The role of
      depression in the identification of mixed emotional signals with a direct
      interpersonal value remains unclear. The present study aimed to clarify this
      question. METHODS: A sample of 39 individuals reporting a broad range of
      depression levels completed an emotion identification task where they viewed
      faces expressing three emotional categories (100% disgusted and 100% happy faces,
      as well as their morphed 50% disgusted - 50% happy exemplars). Participants were
      asked to identify the corresponding depicted emotion as "clearly disgusted",
      "mixed", or "clearly happy". RESULTS: Higher depression levels were associated
      with lower identification of positive emotions in 50% disgusted - 50% happy
      faces. LIMITATIONS: The study was conducted with an analogue sample reporting
      individual differences in subclinical depression levels. Further research must
      replicate these findings in a clinical sample and clarify whether differential
      emotional identification patterns emerge in depression for different mixed
      negative-positive emotions (sad-happy vs. disgusted-happy). CONCLUSIONS:
      Depression may account for a lower bias to perceive positive states when
      ambiguous states from others include subtle signals of social threat (i.e.,
      disgust), leading to an under-perception of positive social signals.

PMID- 28499120
TI  - Characterising bias in regulatory risk and decision analysis: An analysis of
      heuristics applied in health technology appraisal, chemicals regulation, and
      climate change governance.
AB  - In many environmental and public health domains, heuristic methods of risk and
      decision analysis must be relied upon, either because problem structures are
      ambiguous, reliable data is lacking, or decisions are urgent. This introduces an
      additional source of uncertainty beyond model and measurement error - uncertainty
      stemming from relying on inexact inference rules. Here we identify and analyse
      heuristics used to prioritise risk objects, to discriminate between signal and
      noise, to weight evidence, to construct models, to extrapolate beyond datasets,
      and to make policy. Some of these heuristics are based on causal generalisations,
      yet can misfire when these relationships are presumed rather than tested (e.g.
      surrogates in clinical trials). Others are conventions designed to confer
      stability to decision analysis, yet which may introduce serious error when
      applied ritualistically (e.g. significance testing). Some heuristics can be
      traced back to formal justifications, but only subject to strong assumptions that
      are often violated in practical applications. Heuristic decision rules (e.g.
      feasibility rules) in principle act as surrogates for utility maximisation or
      distributional concerns, yet in practice may neglect costs and benefits, be based
      on arbitrary thresholds, and be prone to gaming. We highlight the problem of rule
      entrenchment, where analytical choices that are in principle contestable are
      arbitrarily fixed in practice, masking uncertainty and potentially introducing
      bias. Strategies for making risk and decision analysis more rigorous include:
      formalising the assumptions and scope conditions under which heuristics should be
      applied; testing rather than presuming their underlying empirical or theoretical
      justifications; using sensitivity analysis, simulations, multiple bias analysis,
      and deductive systems of inference (e.g. directed acyclic graphs) to characterise
      rule uncertainty and refine heuristics; adopting "recovery schemes" to correct
      for known biases; and basing decision rules on clearly articulated values and
      evidence, rather than convention.

PMID- 28499121
TI  - Molecular characterization of O157:H7, O26:H11 and O103:H2 Shiga toxin-producing
      Escherichia coli isolated from dairy products.
AB  - Pathogenic Shiga toxin-producing E. coli (STEC) are recognized worldwide as
      environment and foodborne pathogens which can be transmitted by ingestion of
      ready-to-eat food such as raw milk-derived products. STEC show a prevalence rate
      in dairy products of 0.9%, yet comparably few outbreaks have been related to
      dairy products consumption. In this study, we used rt-qPCR to identify the
      virulence potential of O157, O26 and O103 STEC strains isolated from raw-milk
      dairy products by analyzing virulence-related gene frequencies and associations
      with O-island (OI) 44, OI-48, OI-50, OI-57, OI-71 and OI-122. Results showed that
      100% of STEC strains investigated harbored genes associated with EHEC-related
      virulence profile patterns (eae and stx, with either espK, espV, ureD and/or
      Z2098). We also found similarities in virulence-related gene content between
      O157:H7 and O103:H2 dairy and non-dairy STEC strains, especially isolates from
      human cases. The O26:H11-serotype STEC strains investigated harbor the arcA
      allele 2 gene associated with specific genetic markers. These profiles are
      associated with high-virulence seropathotype-A STEC. However, the low frequency
      of stx2 gene associated with absence of other virulence genes in dairy isolates
      of O26:H11 remains a promising avenue of investigation to estimate their real
      pathogenicity. All O26:H11 attaching-effacing E. coli (AEEC) strains carried
      CRISPRO26:H11SP_O26_E but not genetic markers espK, espV, ureD and/or Z2098
      associated with the emerging potentially high-virulence "new French clone". These
      strains are potentially as "EHEC-like" strains because they may acquire (or have
      lost) stx gene. In this study, O157:H7, O103:H2 and O26:H11 STEC strains isolated
      from dairy products were assigned as potential pathogens. However, research now
      needs to investigate the impact of dairy product environment and dairy processing
      on the expression of their pathogenicity.

PMID- 28499122
TI  - EMD-DWT based transform domain feature reduction approach for quantitative multi
      class classification of breast lesions.
AB  - Using a large set of ultrasound features does not necessarily ensure improved
      quantitative classification of breast tumors; rather, it often degrades the
      performance of a classifier. In this paper, we propose an effective feature
      reduction approach in the transform domain for improved multi-class
      classification of breast tumors. Feature transformation methods, such as
      empirical mode decomposition (EMD) and discrete wavelet transform (DWT), followed
      by a filter- or wrapper-based subset selection scheme are used to extract a set
      of non-redundant and more potential transform domain features through
      decorrelation of an optimally ordered sequence of N ultrasonic bi-modal (i.e.,
      quantitative ultrasound and elastography) features. The proposed transform domain
      bi-modal reduced feature set with different conventional classifiers will
      classify 201 breast tumors into benign-malignant as well as BI-RADS?3, 4, and 5
      categories. For the latter case, an inadmissible error probability is defined for
      the subset selection using a wrapper/filter. The classifiers use train truth from
      histopathology/cytology for binary (i.e., benign-malignant) separation of tumors
      and then bi-modal BI-RADS scores from the radiologists for separating malignant
      tumors into BI-RADS category 4 and 5. A comparative performance analysis of
      several widely used conventional classifiers is also presented to assess their
      efficacy for the proposed transform domain reduced feature set for classification
      of breast tumors. The results show that our transform domain bimodal reduced
      feature set achieves improvement of 5.35%, 3.45%, and 3.98%, respectively, in
      sensitivity, specificity, and accuracy as compared to that of the original domain
      optimal feature set for benign-malignant classification of breast tumors. In
      quantitative classification of breast tumors into BI-RADS categories?3, 4, and 5,
      the proposed transform domain reduced feature set attains improvement of 3.49%,
      9.07%, and 3.06%, respectively, in likelihood of malignancy and 4.48% in
      inadmissible error probability compared to that of the original domain optimal
      subset. In summary, the construction of a transform domain reduced feature set by
      extracting complementary information from a large set of available bi-modal
      features and use of qualitative bi-modal BI-RADS can contribute to improved
      quantitative classification of breast tumors and thereby help reduce the number
      of unnecessary biopsies, securing a nearly minimum chance of a life-endangering
      diagnosis.

PMID- 28499123
TI  - Self-action of propagating and standing Lamb waves in the plates exhibiting
      hysteretic nonlinearity: Nonlinear zero-group velocity modes.
AB  - An analytical theory accounting for the influence of hysteretic nonlinearity of
      micro-inhomogeneous plate material on the Lamb waves near the S1 zero group
      velocity point is developed. The theory predicts that the main effect of the
      hysteretic quadratic nonlinearity consists in the modification of the frequency
      and the induced absorption of the Lamb modes. The effects of the nonlinear self
      action in the propagating and standing Lamb waves are expected to be,
      respectively, nearly twice and three times stronger than those in the plane
      propagating acoustic waves. The theory is restricted to the simplest hysteretic
      nonlinearity, which is influencing only one of the Lame moduli of the materials.
      However, possible extensions of the theory to the cases of more general
      hysteretic nonlinearities are discussed as well as the perspectives of its
      experimental testing. Applications include nondestructive evaluation of micro
      inhomogeneous and cracked plates.

PMID- 28499124
TI  - Peri-ultrasound for modeling linear and nonlinear ultrasonic response.
AB  - The objective of this paper is to introduce a novel fast modeling tool called
      peri-ultrasound for linear/nonlinear ultrasonic wave propagation modeling. This
      modeling approach is based on peridynamic theory. It does not require monitoring
      of the crack clapping phenomenon or artificially changing the stiffness of the
      element when two surfaces of the crack come in contact. Peri-ultrasound tool
      enables us to detect the material nonlinearity in very early stages of crack
      growth. Nonlinear ultrasonic behavior could be nicely modeled by the proposed
      peri-ultrasound tool. It is investigated how the material nonlinearity is
      affected by the presence of thin and thick cracks. From the normalized spectral
      plots the degree of material nonlinearity can be measured by extracting a feature
      called sideband peak count (SPC). Structures containing a thin crack show
      noticeable increase in their nonlinear behavior.

PMID- 28499125
TI  - Statistics associated with the scattering of ultrasound from microstructure.
AB  - The spatial statistics of an ensemble of waveforms containing ultrasonic
      scattering from microstructure are investigated. The standard deviation of the
      waveforms is of primary interest, because it is related to the maximum scattering
      amplitudes in the extreme value statistics theory. Further statistical measures
      are employed to define theoretical confidence bounds, which bound the
      experimentally calculated maximum amplitude when a finite number of waveforms are
      included in the ensemble. These statistical measures are applied in conjunction
      with a previously developed ultrasonic backscatter model. It is validated through
      ultrasonic scattering measurements performed on a stainless-steel pipe sample.
      These considerations are important for forward models related to the probability
      of detection (POD) of defects and inverse models used for characterization of
      polycrystalline microstructures.

PMID- 28499127
TI  - 3D-printed scaffolds with synergistic effect of hollow-pipe structure and
      bioactive ions for vascularized bone regeneration.
AB  - Segmental bone regeneration remains a considerable challenge due to the
      associated low degree of vascularization. To solve this problem, in this study,
      hollow-pipe-packed silicate bioceramic (BRT-H) scaffolds are fabricated using a
      coaxial three-dimensional (3D) printing technique. Based on a modified core/shell
      printer nozzle and a modulated viscoelastic bioceramic paste, hollow struts with
      an external diameter of 1 mm and internal dimeter of 500 MUm can be directly
      printed, yielding a compressive strength of the BRT-H scaffolds as high as 26
      MPa. Apart from the effects on osteogenesis, the bioactive ions released from the
      BRT scaffolds can also facilitate angiogenesis via inducing endothelial cell
      migration. More importantly, the hollow pipes not only significantly promote the
      rapid infiltration of host blood vessels into the channels but also exhibit great
      advantages for the delivery of stem cells and growth factors to further enhance
      tissue regeneration. When used for the regeneration of rabbit radius segmental
      defects, radiological and histological findings indicate that the BRT-H scaffolds
      can enhance early vascularization and later bone regeneration and remodeling.
      Taken together, the hollow pipes and the ionic products from BRT-H scaffolds have
      a synergistic effect on enhancing vascularized bone regeneration.

PMID- 28499126
TI  - Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells.
AB  - Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence
      of its ligands for autonomous stimulation of oncogenic signaling. Previous
      studies raise the possibility that cancer cell NKG2D may induce high malignancy
      traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer
      as model setting, we show here that ex vivo NKG2D+ cancer cells have stem-like
      capacities, and provide formal in vivo evidence linking NKG2D stimulation with
      the development and maintenance of these functional states. NKG2D+ ovarian cancer
      cell populations harbor substantially greater capacities for self-renewing in
      vitro sphere formation and in vivo tumor initiation in immunodeficient (NOD scid
      gamma) mice than NKG2D- controls. Sphere formation and tumor initiation are
      impaired by NKG2D silencing or ligand blockade using antibodies or a newly
      designed pan ligand-masking NKG2D multimer. In further support of
      pathophysiological significance, a prospective study of 47 high-grade serous
      ovarian cancer cases revealed that the odds of disease recurrence were
      significantly greater and median progression-free survival rates higher among
      patients with above and below median NKG2D+ cancer cell frequencies,
      respectively. Collectively, our results define cancer cell NKG2D as an important
      regulator of tumor initiation in ovarian cancer and presumably other malignancies
      and thus challenge current efforts in immunotherapy aimed at enhancing NKG2D
      function.

PMID- 28499128
TI  - Stress induced by heavy metals on breeding of magpie (Pica pica) from central
      Iran.
AB  - The aim of this study was to address the impacts of some heavy metals (Cd, Pb,
      Zn, Ni and Cu) contamination on laying behavior, egg quality and breeding
      performance of Pica pica in north of Isfahan Province, Iran. During the breeding
      season of 2013, magpie's egg content and eggshell as well as nestling excrements
      and feathers were collected and total concentrations of heavy metals were
      measured by ICP-OES. Except for Zn in nestling feathers, the significantly higher
      concentrations of heavy metals were observed in nestling excrements than other
      samples. Also, comparison of heavy metals concentrations in egg content and
      eggshell showed that egg content had significantly higher concentrations of Zn
      and Pb, instead eggshell had significantly higher amount of Cu and Cd. Except for
      Cu, all heavy metals concentrations in eggshell had a negative relationship with
      morphological characters; and also concentration of Cu in egg content showed a
      significantly negative correlation with egg weight and volume. The most of heavy
      metals in nestling feathers and excrements had strongly positive correlations
      with each other. Also all heavy metals levels in eggshell and egg content had
      significantly positive correlations (except for Cu). Unhatched eggs had
      significantly lower weight but also greater levels of Zn, Cd, and Pb, than
      randomly collected eggs. No significant differences were observed for
      morphometric measurements of eggs between different sites, however, a decreased
      gradient was observed in egg volume toward the brick kiln site. Samples collected
      in brick kiln site accumulated higher concentrations of heavy metals than other
      sites. Although numbers of clutch size in brick kiln site were significantly
      higher than other sites, however, other breeding variable were lower than other
      sites. It can be suggested that ecosystem contamination may be caused to decrease
      the reproduction rate of Pica pica in brick kiln, probably by laying more poor
      quality eggs per clutch and nestling mortality.

PMID- 28499129
TI  - Occurrence of antimicrobial resistance bacteria in the Yodo River basin, Japan
      and determination of beta-lactamases producing bacteria.
AB  - Antimicrobial resistant bacteria are widespread in aquatic environments. The aim
      of the present study was to obtain information on the occurrence of bacteria with
      antimicrobial resistance and their multiple antimicrobial resistance (MAR)
      patterns in a river basin in Japan. In addition, the occurrence of fecal bacteria
      producing extended-spectrum beta-lactamases (ESBLs) and metallo-beta-lactamase
      (MBL) in the aquatic environment was determined. Among the Escherichia coli
      isolates recovered from river samples upstream, 55% isolates were resistant to at
      least one antimicrobial and 18% were MAR. Among the E. coli isolates recovered
      from wastewater treatment plant (WWTP) effluent samples, 74% isolates were
      resistant to at least one antimicrobial and 46% were MAR. These findings suggest
      that the presence of WWTP effluent will increase the degree of contamination with
      MAR in the aquatic environment. Among the ampicillin-resistant isolates recovered
      from river samples, 21% isolates were judged as ESBL-producing and none (0%) was
      judged as MBL-producing. Among the ampicillin-resistant isolates recovered from
      WWTP effluent samples, 21% were judged as ESBL-producing and 1% was judged as MBL
      producing. As for the hospital wastewater samples, 48% were judged as ESBL
      producing and 3% were judged as MBL-producing. The percentage of ESBLs and MBL
      production was highest in hospital wastewater samples. All of the ESBL-producing
      isolates detected had resistance to ampicillin, cephazolin, and cefpodoxime and
      many ESBL-producers had resistance not only to beta-lactams but also to other
      kinds of antimicrobials such as aminoglycosides and quinolones. The frequency of
      detection of MBL-producers was much lower than that of ESBL-producers and MBL
      producers were not detected in the river samples. However, the detection in WWTP
      effluent samples indicated that bacteria with MBL were present downstream of the
      WWTP at low concentrations. Thus, ESBLs and MBL have already been spread around
      aquatic environments.

PMID- 28499130
TI  - Extracorporeal membrane oxygenation (ECMO) as a treatment strategy for severe
      acute respiratory distress syndrome (ARDS) in the low tidal volume era: A
      systematic review.
AB  - OBJECTIVE: To evaluate the hospital survival in patients with severe ARDS managed
      with ECMO and low tidal volume ventilation as compared to patients managed with
      low tidal volume ventilation alone. METHODS: Electronic databases were searched
      for studies of at least 10 adult patients with severe ARDS comparing the use of
      ECMO with low tidal volume ventilation to mechanical ventilation with a low tidal
      volume alone. Only studies reporting hospital or ICU survival were included. All
      identified studies were assessed independently by two reviewers. RESULTS: Of 1782
      citations, 27 studies (n=1674) met inclusion criteria. Hospital survival for ECMO
      patients ranged from 33.3 to 86%, while survival with conventional therapy ranged
      from 36.3 to 71.2%. Five studies were identified with appropriate control groups
      allowing comparison, but due to the high degree of variability between studies
      (I2=63%), their results could not be pooled. Two of these studies demonstrated a
      significant difference, both favouring ECMO over conventional therapy.
      CONCLUSION: Given the lack of studies with appropriate control groups, our
      confidence in a difference in outcome between the two therapies remains weak.
      Future studies on the use of ECMO for severe ARDS are needed to clarify the role
      of ECMO in this disease.

PMID- 28499131
TI  - Polyphyly in the Thecate Amoeba Genus Lecythium (Chlamydophryidae, Tectofilosida,
      Cercozoa), Redescription of its Type Species L. hyalinum, Description of L.
      jennyae sp. nov. and the Establishment of Fisculla gen. nov. and Fiscullidae fam.
      nov.
AB  - Although testate amoebae have attracted great interest of protistologists for
      more than a century, some groups, especially those with a hyaline, organic test
      (=theca) are still poorly known. One of those is the genus Lecythium Hertwig et
      Lesser, 1874. Only recently Lecythium spp. were characterized by morphological
      and molecular means, but data on the type species Lecythium hyalinum Hertwig et
      Lesser, 1874, was still lacking. In this study, we screened for L. hyalinum in
      freshwater samples of Germany and the Netherlands. Four different isolates of L.
      hyalinum and one novel species were cultured and characterized by light
      microscopy. Phylogenetic analyses based on the small ribosomal subunit (SSU) RNA
      gene show that the genus Lecythium forms two robust clades, one forming a sister
      group to the Rhizaspididae/Pseudodifflugiidae clade (Tectofilosida), the other
      branching within 'Novel Clade 4' (Tectofilosida). We untangle this polyphyly by
      establishing Fisculla gen. nov. and the Fiscullidae fam. nov. for the former of
      these two clades.

PMID- 28499133
TI  - Value of digit ratio 2D:4D, a biomarker of prenatal hormone exposure, is stable
      across the menstrual cycle.
AB  - Digit ratio (2D:4D) is used as a marker of prenatal hormone exposure and,
      consequently, as a predictor of many characteristics throughout a woman's
      lifespan. A previous study has suggested that values of 2D:4D vary across
      menstrual cycles and further questioned the reliability of a single measurement
      of 2D:4D among cycling women, while another study failed to confirm these
      results. However, these studies estimated the timing of cycle phases based on a
      date of menstruation reported by participants and also had small sample sizes.
      For our study, we evaluated potential changes in 2D:4D values across a menstrual
      cycle in a group of women among whom the phases of the menstrual cycle were
      determined by hormonal (luteinizing hormone based) ovulation tests. We studied 32
      naturally cycling women aged 22-37 from rural Poland. Lengths of second and
      fourth digits were measured based on scans of both hands taken three times (i.e.
      in the follicular phase, peri-ovulatory phase and luteal phase of the cycle) for
      each participant. No differences in 2D:4D value across the menstrual cycle were
      detected either when right-hand, left-hand, and mean 2D:4D for both hands were
      analysed, nor when difference in the 2D:4D value between hands (Dleft-right) was
      evaluated. We documented that 2D:4D is independent of the phase of the menstrual
      cycle and these findings suggest that among naturally cycling women, a value of
      2D:4D can be reliably obtained from measurements taken during any day of the
      menstrual cycle.

PMID- 28499134
TI  - Digit ratio (2D:4D) and postoperative pain perception.
AB  - BACKGROUNDS: It has not been established whether sex differences in pain
      perception are influenced by prenatal sex hormones. Digit ratio as an indicator
      of prenatal hormone exposure can be used as a simple measure of the influence of
      prenatal hormones on pain sensitivity or perception in adulthood. OBJECTIVE: The
      aim of this study was to determine a correlation between the 2D:4D ratio and pain
      perception in the postoperative period after rhinoplasty. METHOD: A prospective
      cohort study of 100 patients (50 women of the mean age of 30.74+/-8.09years and
      50 men of the mean age of 30.98+/-10.86years) who underwent posttraumatic
      rhinoplasty due to the nose trauma in Plastic, Reconstructive and Aesthetic
      Surgery Clinic. The following measurements were taken the day before a surgery:
      body height, waist and hip circumference, II and IV digits' lengths and body
      weight. All subjects filled in a questionnaire including 0-10-point VAS scales to
      assess postoperative pain 1h after an operation (AO), 6h AO, 12h AO, 24h AO and
      48h AO. RESULTS: Women with low 2D:4D reported significantly more pain 1h after
      an operation than women with high 2D:4D. Similar correlation was observed for low
      2D:4D in women 48h AO. In men, low 2D:4D was associated with lower postoperative
      pain 12h AO (p=0.029). CONCLUSION: In conclusion, we showed that low 2D:4D in
      women was associated with high postoperative pain, and low right 2D:4D in men was
      associated with low postoperative pain. This may suggest that intrauterine
      estrogen exposure makes women more resistant to pain.

PMID- 28499132
TI  - Multiple Dictyostelid Species Destroy Biofilms of Klebsiella oxytoca and Other
      Gram Negative Species.
AB  - Dictyostelids are free-living phagocytes that feed on bacteria in diverse
      habitats. When bacterial prey is in short supply or depleted, they undergo
      multicellular development culminating in the formation of dormant spores. In this
      work, we tested isolates representing four dictyostelid species from two genera
      (Dictyostelium and Polysphondylium) for the potential to feed on biofilms
      preformed on glass and polycarbonate surfaces. The abilities of dictyostelids
      were monitored for three hallmarks of activity: 1) spore germination on biofilms,
      2) predation on biofilm enmeshed bacteria by phagocytic cells and 3)
      characteristic stages of multicellular development (streaming and
      fructification). We found that all dictyostelid isolates tested could feed on
      biofilm enmeshed bacteria produced by human and plant pathogens: Klebsiella
      oxytoca, Pseudomonas aeruginosa, Pseudomonas syringae, Erwinia amylovora 1189
      (biofilm former) and E. amylovora 1189 Deltaams (biofilm deficient mutant).
      However, when dictyostelids were fed planktonic E. amylovora Deltaams the
      bacterial cells exhibited an increased susceptibility to predation by one of the
      two dictyostelid strains they were tested against. Taken together, the
      qualitative and quantitative data presented here suggest that dictyostelids have
      preferences in bacterial prey which affects their efficiency of feeding on
      bacterial biofilms.

PMID- 28499135
TI  - Pain threshold, tolerance and intensity in adolescents born very preterm or with
      low birth weight.
AB  - BACKGROUND: Data on long-term consequences of neonatal pain is limited. AIM: To
      assess whether perinatal factors, later pain experience and pain coping
      strategies are associated with altered pain threshold, pain tolerance and pain
      intensity in adolescents born preterm. STUDY DESIGN: Observational, longitudinal
      study (Project on Preterm and SGA-infants, POPS-19). SUBJECTS: We analyzed data
      of 412 adolescents at the age of 19years, who were born at a gestational
      age<32weeks or with a birth weight<1500g. OUTCOME MEASURES: Participants
      performed a standardized cold pressor test to assess pain threshold, tolerance
      and intensity. Furthermore, they completed a pain coping questionnaire (PCQ).
      RESULTS: In univariate analysis, female gender and necrotizing enterocolitis
      (NEC) were associated with lower pain tolerance, indicated by reaching the
      ceiling time of 180s in ice water (females 19% vs males 29%, NEC 7% vs no NEC
      25%). Female gender was associated with higher pain intensity (mean difference
      0.58; 95%CI 0.21; 0.95) and lower pain threshold (log rank test p 0.007). In a
      multivariate Cox regression analyses, emotion focused avoidance pain coping style
      was significantly associated with lower pain threshold (hazard ratio HR 1.38;
      95%CI 1.02; 1.87) and pain tolerance (HR 1.72; 95%CI 1.21; 2.42). NEC was
      significantly associated with lower pain threshold (HR 1.47; 95%CI 1.01; 2.14)
      and pain tolerance (HR 1.63; 95%CI 1.09; 2.41). CONCLUSION: In adolescence,
      maladaptive pain coping strategy was associated with lower pain threshold, pain
      tolerance and higher pain intensity. NEC was associated with altered pain
      response in adolescents born preterm.

PMID- 28499136
TI  - A novel tool for the identification of correlations in medical data by faceted
      search.
AB  - This work focuses on the integration of multifaceted extensive data sets (e.g.
      laboratory values, vital data, medications) and partly unstructured medical data
      such as discharge letters, diagnostic reports, clinical notes etc. in a research
      database. Our main application is an integrated faceted search in nephrology
      based on information extraction results. We describe the details of the
      application of transplant medicine and the resulting technical architecture of
      the faceted search application.

PMID- 28499137
TI  - A comparison of the ground reaction force frequency content during rearfoot and
      non-rearfoot running patterns.
AB  - Running with a non-rearfoot pattern has been claimed to reduce injury risk
      because the impact peak in the vertical ground reaction force (GRF) is visually
      absent in the time-domain compared with a rearfoot pattern. However, running
      results in a rapid deceleration of the lower extremity segments immediately
      following initial contact with the ground, regardless of footfall pattern.
      Therefore, the frequency content of the GRF is expected to contain evidence of
      this collision. The purpose of the present study was to characterize the waveform
      components of the GRF generated during the impact phase by habitual rearfoot and
      habitual non-rearfoot pattern groups using the continuous wavelet transform.
      Twenty rearfoot and 20 non-rearfoot participants ran over-ground at a
      standardized speed with their habitual footfall pattern. The continuous wavelet
      transform was performed on the resultant GRF vector and the vertical GRF. GRF
      signals generated by the non-rearfoot pattern group during early stance had
      maximum signal power of 15.4+/-9.1Hz occurring at 23.1+/-6.3% of stance, which is
      within the 10-20Hz range previously associated with impact in rearfoot runners.
      Maximum signal power occurred earlier in the impact phase (11.5+/-1.5%) and with
      a higher frequency (27.2+/-3.9Hz) in the rearfoot pattern group verses the non
      rearfoot pattern group (P<0.05). While the impact force transient may not appear
      as a prominent feature within the time-domain GRF with a non-rearfoot pattern,
      the results indicate that both footfall patterns generate frequencies associated
      with the impact peak in the resultant and vertical GRF.

PMID- 28499138
TI  - Human pegivirus-1 in the CSF of patients with HIV-associated neurocognitive
      disorder (HAND) may be derived from blood in highly viraemic patients.
AB  - BACKGROUND: Human pegivirus-1 (HPgV-1) infection in the brain has not been
      extensively examined and its association with disease remains unconfirmed. In a
      high throughput sequencing study to look for infectious agents that could play a
      role in HIV-associated neurocognitive disorder (HAND), this virus was detected in
      3 of 8 CSF samples. OBJECTIVES: To determine the significance of this finding,
      additional patients were screened and the viral load and viral diversity in blood
      and CSF were examined. STUDY DESIGN: Nested PCR of the viral 5'NCR region was
      performed on blood and CSF pairs from 16 HAND patients. PCR products were cloned,
      sequenced and analysed to determine viral diversity in blood and CSF. HPgV-1
      viral loads were determined in paired blood and CSF of 2 patients by digital
      droplet PCR. Nested PCR was also performed on CSF samples from patients with
      other brain disorders. RESULTS: Virus was detected in both blood and CSF in 3 of
      16 HAND patients. Viral loads were very high in blood (8.81 and 10.56 log
      copies/ml) and 4-5 logs lower in CSF (4.68 and 5.84 log copies/ml). Sequence
      analysis of 5'NCR clones in blood and CSF showed limited variation. The dominant
      viral variant (based on clonal sequence identity) in blood and CSF was usually
      identical. HPgV-1 was detected in CSF from patients with other brain disorders at
      a similar frequency (15% versus 18.75% in HAND patients). CONCLUSION: While
      several studies have reported HPgV-1 detection in CSF of patients with brain
      disease, this is the only study that has examined both blood and CSF compartments
      simultaneously. Our findings show that virus in CSF always coincided with
      viraemia and levels were 4-5 logs higher in blood. While a rare, but specific
      brain tropism cannot be excluded, blood is the more probable source of virus in
      HAND patients.

PMID- 28499139
TI  - A novel form of perceptual attunement: Context-dependent perception of a native
      contrast in 14-month-old infants.
AB  - By the end of their first year of life, infants have become experts in
      discriminating the sounds of their native language, while they have lost the
      ability to discriminate non-native contrasts. This type of phonetic learning is
      referred to as perceptual attunement. In the present study, we investigated the
      emergence of a context-dependent form of perceptual attunement in infancy.
      Indeed, some native contrasts are not discriminated in certain phonological
      contexts by adults, due to the presence of a language-specific process that
      neutralizes the contrasts in those contexts. We used a mismatch design and
      recorded high-density Electroencephalography (EEG) in French-learning 14-month
      olds. Our results show that similarly to French adults, infants fail to
      discriminate a native voicing contrast (e.g., [f] vs. [v]) when it occurs in a
      specific phonological context (e.g. [ofbe] vs. [ovbe], no mismatch response),
      while they successfully detected it in other phonological contexts (e.g., [ofne]
      vs. [ovne], mismatch response). The present results demonstrate for the first
      time that by the age of 14 months, infants' phonetic learning does not only rely
      on the processing of individual sounds, but also takes into account in a language
      specific manner the phonological contexts in which these sounds occur.

PMID- 28499140
TI  - Is vehicle automation enough to prevent crashes? Role of traffic operations in
      automated driving environments for traffic safety.
AB  - Automated driving systems (ADSs) are expected to prevent traffic accidents caused
      by driver carelessness on freeways. There is no doubt regarding this safety
      benefit if all vehicles in the transportation system were equipped with ADSs;
      however, it is implausible to expect that ADSs will reach 100% market penetration
      rate (MPR) in the near future. Therefore, the following question arises: 'Can
      ADSs, which consider only situations in the vicinity of an equipped vehicle,
      really contribute to a significant reduction in traffic accidents?' To address
      this issue, the interactions between equipped and unequipped vehicles must be
      investigated, which is the purpose of this study. This study evaluated traffic
      safety at different MPRs based on a proposed index to represent the overall rear
      end crash risk of the traffic stream. Two approaches were evaluated for adjusting
      longitudinal vehicle maneuvers: vehicle safety-based maneuvering (VSM), which
      considers the crash risk of an equipped vehicle and its neighboring vehicles, and
      traffic safety-based maneuvering (TSM), which considers the overall crash risk in
      the traffic stream. TSM assumes that traffic operational agencies are able to
      monitor all the vehicles and to intervene in vehicle maneuvering. An optimization
      process, which attempts to obtain vehicle maneuvering control parameters to
      minimize the overall crash risk, is integrated into the proposed evaluation
      framework. The main purpose of employing the optimization process for vehicle
      maneuvering in this study is to identify opportunities to improve traffic safety
      through effective traffic management rather than developing a vehicle control
      algorithm that can be implemented in practice. The microscopic traffic simulator
      VISSIM was used to simulate the freeway traffic stream and to conduct systematic
      evaluations based on the proposed methodology. Both TSM and VSM achieved
      significant reductions in the potential for rear-end crashes. However, TSM
      obtained much greater reductions when the MPR was greater than 50%. This study
      should inspire transportation researchers and engineers to develop effective
      traffic operations strategies for automated driving environments.

PMID- 28499141
TI  - Can vehicle longitudinal jerk be used to identify aggressive drivers? An
      examination using naturalistic driving data.
AB  - This paper investigated the characteristics of vehicle longitudinal jerk (change
      rate of acceleration with respect to time) by using vehicle sensor data from an
      existing naturalistic driving study. The main objective was to examine whether
      vehicle jerk contains useful information that could be potentially used to
      identify aggressive drivers. Initial investigation showed that there are unique
      characteristics of vehicle jerk in drivers' gas and brake pedal operations. Thus
      two jerk-based metrics were examined: (1) driver's frequency of using large
      positive jerk when pressing the gas pedal, and (2) driver's frequency of using
      large negative jerk when pressing the brake pedal. To validate the performance of
      the two metrics, drivers were firstly divided into an aggressive group and a
      normal group using three classification methods (1) traveling at excessive speed
      (speeding), (2) following too closely to a front vehicle (tailgating), and (3)
      their association with crashes or near-crashes in the dataset. The results show
      that those aggressive drivers defined using any of the three methods above were
      associated with significantly higher values of the two jerk-based metrics.
      Between the two metrics the frequency of using large negative jerk seems to have
      better performance in identifying aggressive drivers. A sensitivity analysis
      shows the findings were largely consistent with varying parameters in the
      analysis. The potential applications of this work include developing quantitative
      surrogate safety measures to identify aggressive drivers and aggressive driving,
      which could be potentially used to, for example, provide real-time or post-ride
      performance feedback to the drivers, or warn the surrounding drivers or vehicles
      using the connected vehicle technologies.

PMID- 28499142
TI  - Does mindfulness prepare adolescents for value-behavior concordance? Examining
      the role of value content.
AB  - Great thinkers throughout history advocated living one's values, yet little
      research has examined factors that contribute to adolescents' value-behavior
      concordance (VBC). Mindfulness may foster VBC via heightened awareness of values,
      but VBC for intrinsic values may be more adaptive than VBC for extrinsic values.
      To situate mindfulness in developmental context, we examined age and attachment
      security as predictors of mindfulness. We collected self- and parent-report data
      from 299 families (Mage-adolescents = 14.45, SD = 1.68; 51% female) from 42 US
      states to test these ideas. Results indicated that mindfulness was positively
      associated with intrinsic VBC but was negatively linked with extrinsic VBC, and
      both kinds of VBC partially mediated the link from mindfulness to meaning (but
      not life satisfaction). Attachment security was associated with higher
      mindfulness. Overall, mindfulness may deliver its benefits by helping young
      people avoid behaviors that align with extrinsic values.

PMID- 28499143
TI  - Differences between clinician- and self-administered shoulder sustained
      mobilization on scapular and shoulder muscle activity during shoulder abduction:
      A repeated-measures study on asymptomatic individuals.
AB  - BACKGROUND: Sustained glenohumeral postero-lateral glide administered by a
      clinician is commonly used in the management of patients with shoulder pain. This
      technique reduced shoulder muscle activity in asymptomatic individuals, but it is
      unknown whether a self-administered version of the mobilization leads to similar
      neuromuscular response. This study compared the effect of sustained shoulder
      mobilizations (performed by a physiotherapist) with self-administered
      mobilization (with a belt) on activity levels of scapular and glenohumeral
      shoulder muscles. METHODS: Twenty-two individuals participated in this study,
      which had a cross-over, repeated measures design. Seven shoulder muscles (upper
      and lower trapezius, supraspinatus, infraspinatus, posterior deltoid, middle
      deltoid, and serratus anterior) were monitored using surface electromyography
      (SEMG) during shoulder abduction performed with a clinician-administered
      sustained mobilization, and with self-administered sustained mobilization. Muscle
      activity levels were measured prior, during and after the sustained glide was
      applied to the shoulder. Mixed-effect models for repeated measures were used for
      within- and between-condition comparisons. RESULTS: There was no carry-over
      effect. Within-condition comparisons suggest that both interventions lead to
      changes in scapular and shoulder muscle activity levels. No differences between
      clinician-administered and self-administered mobilizations at intervention and
      follow-up were found for the monitored muscles, with the exception of upper
      trapezius. CONCLUSIONS: In young, asymptomatic individuals, self- or clinician
      administered sustained mobilizations reduced activity levels of most scapular and
      shoulder muscles during shoulder abduction. This effect was observed only while
      the sustained glides were applied to the shoulder. At the immediate follow-up,
      muscle activity levels were similar to baseline measurements.

PMID- 28499144
TI  - Patterns of response to scrambled scenes reveal the importance of visual
      properties in the organization of scene-selective cortex.
AB  - Neuroimaging studies have found distinct patterns of neural response to different
      categories of scene in scene-selective regions of the human brain. However, it is
      not clear how information about scene category is represented in these regions.
      Images from different categories vary systematically in their visual properties
      as well as their semantic category. So, it is possible that patterns of neural
      response could reflect variation in visual properties. To address this question,
      we used fMRI to measure patterns of neural response to intact and scrambled scene
      categories. Although scrambling preserved many of their visual characteristics,
      perception of scene categories was severely impaired. Nevertheless, we found
      distinct patterns of response to different scene categories in the
      parahippocampal place area (PPA) and the occipital place area (OPA) for both
      intact and scrambled scenes. Moreover, intact and scrambled scenes produced
      highly similar patterns of response. Our finding that reliable and distinct
      patterns of response in scene-selective regions are still evident when
      categorical perception is impaired suggests that visual properties play an
      important role in the topographic organization of these regions.

PMID- 28499145
TI  - Human dorsomedial parieto-motor circuit specifies grasp during the planning of
      goal-directed hand actions.
AB  - According to one influential view, two specialized parieto-frontal circuits
      control prehension: a dorsomedial stream for hand transport during reaching and a
      dorsolateral stream for preshaping the fingers during grasping. However, recent
      evidence argues that an area within the dorsomedial stream-macaque area V6A and,
      its putative human homolog, superior parietal occipital cortex (SPOC) - encodes
      both hand transport and grip formation. We tested whether planning varied hand
      actions modulates functional connectivity between left SPOC and ipsilateral
      primary motor cortex (M1) using a dual-site, paired-pulse transcranial magnetic
      stimulation paradigm with two coils (dsTMS). Participants performed three
      different hand actions to a target object comprising a small cylinder atop a
      larger cylinder. These actions were: reaching-to-grasp the top (GT) using a
      precision grip, reaching-to-grasp the bottom (GB) using a whole-hand grip, or
      reaching-to-touch (Touch) the side of the target object without forming a grip.
      Motor-evoked potentials (MEPs) from TMS to M1, with or without preceding TMS to
      SPOC, were recorded from first dorsal interosseous (FDI) and abductor digiti
      minimi (ADM) hand muscles in two experiments that varied timing parameters (the
      stimulus onset asynchrony, SOA, between the 'GO' cue and stimulation and
      interpulse interval, IPI, between SPOC and M1 stimulation). We found that
      preparatory response amplitudes in the SPOC-M1 circuit of different hand muscles
      were selectively modulated early in the motor plan for different types of grasps.
      First, based on SPOC-M1 interactions, across two experiments, the role of the ADM
      was facilitated during a whole-hand grasp of a large object (GB) relative to
      other conditions under certain timing parameters (SOA = 150 msec; IPI = 6 msec).
      Second, the role of the FDI was facilitated during hand action planning compared
      to rest. These findings suggest that the human dorsomedial parieto-motor stream
      plays a causal role in planning grip formation for object-directed actions.

PMID- 28499146
TI  - RNA sequencing reveals pronounced changes in the noncoding transcriptome of aging
      synaptosomes.
AB  - Normal aging is associated with impairments in cognitive functions. These
      alterations are caused by diminutive changes in the biology of synapses, and
      ineffective neurotransmission, rather than loss of neurons. Hitherto, only a few
      studies, exploring molecular mechanisms of healthy brain aging in higher
      vertebrates, utilized synaptosomal fractions to survey local changes in aging
      related transcriptome dynamics. Here we present, for the first time, a
      comparative analysis of the synaptosomes transcriptome in the aging mouse brain
      using RNA sequencing. Our results show changes in the expression of genes
      contributing to biological pathways related to neurite guidance, synaptosomal
      physiology, and RNA splicing. More intriguingly, we also discovered alterations
      in the expression of thousands of novel, unannotated lincRNAs during aging.
      Further, detailed characterization of the cleavage and polyadenylation factor I
      subunit 1 (Clp1) mRNA and protein expression indicates its increased expression
      in neuronal processes of hippocampal stratum radiatum in aging mice. Together,
      our study uncovers a new layer of transcriptional regulation which is targeted by
      aging within the local environment of interconnecting neuronal cells.

PMID- 28499147
TI  - Fructose increases corticosterone production in association with NADPH metabolism
      alterations in rat epididymal white adipose tissue.
AB  - Metabolic syndrome is an array of closely metabolic disorders that includes
      glucose intolerance/insulin resistance, central obesity, dyslipidemia, and
      hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects
      in adipose tissue, and has been associated with the etiopathology of many
      components of the metabolic syndrome. In adipocytes, the enzyme 11 beta-HSD1
      amplifies local glucocorticoid production, being a key player in the pathogenesis
      of central obesity and metabolic syndrome. 11 beta-HSD1 reductase activity is
      dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic
      reticulum. Our focus was to explore the effect of fructose overload on epididymal
      white adipose tissue (EWAT) machinery involved in glucocorticoid production and
      NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose
      solution (10% (w/v) in tap water) during 9 weeks developed some characteristic
      features of metabolic syndrome, such as hypertriglyceridemia, and hypertension.
      In addition, high levels of plasma and EWAT corticosterone were detected.
      Activities and expressions of H6PD and 11 beta-HSD1, NAPDH content, superoxide
      anion production, expression of NADPH oxidase 2 subunits, and indicators of
      oxidative metabolism were measured. Fructose overloaded rats showed an increased
      potential in oxidant production respect to control rats. In parallel, in EWAT
      from fructose overloaded rats we found higher expression/activity of H6PD and 11
      beta-HSD1, and NADPH/NADP+ ratio. Our in vivo results support that fructose
      overload installs in EWAT conditions favoring glucocorticoid production through
      higher H6PD expression/activity supplying NADPH for enhanced 11 beta-HSD1
      expression/activity, becoming this tissue a potential extra-adrenal source of
      corticosterone under these experimental conditions.

PMID- 28499149
TI  - Home as a place of caring and wellbeing? A qualitative study of informal carers
      and caring networks lived experiences of providing in-home end-of-life care.
AB  - Although the burden of caring is well described, the value of home as a potential
      place of wellbeing and support for informal caring networks when providing end-of
      life care is not well recognised. Interviews and focus groups with 127 primary
      carers and members of informal care networks revealed their collaborative stories
      about caring for a dying person at home. Four themes emerged from the data: home
      as a place of comfort and belonging; places of social connection and
      collaborative caring; places of connection to nature and the non-human; places of
      achievement and triumph. When support is available, nurturing carer wellbeing may
      be best achieved at home.

PMID- 28499148
TI  - Long-term neighborhood poverty trajectories and obesity in a sample of california
      mothers.
AB  - Neighborhoods (and people) are not static, and are instead shaped by dynamic long
      term processes of change (and mobility). Using the Geographic Research on
      Wellbeing survey, a population-based sample of 2339 Californian mothers, we
      characterize then investigate how long-term latent neighborhood poverty
      trajectories predict the likelihood of obesity, taking into account short-term
      individual residential mobility. We find that, net of individual and neighborhood
      level controls, living in or moving to tracts that experienced long-term low
      poverty was associated with lower odds of being obese relative to living in
      tracts characterized by long-term high poverty.

PMID- 28499150
TI  - Effect of yarn structure on wicking and its impact on bloodstain pattern analysis
      (BPA) on woven cotton fabrics.
AB  - Bloodstain pattern analysis (BPA) of bloodstains on hard, non-porous surfaces has
      found widespread use in crime scene analysis and reconstruction for violent
      crimes in which bloodshed occurs. At many violent crime scenes, bloody clothing
      is also found and may be analyzed. However, to date, there are no definitive
      methods for analyzing bloodstains on textiles, even for simple drip stains. There
      are two major classes of textiles used for apparel and household textiles, weaves
      and knits. In this article, drip stains on two 100% cotton plain weave fabrics
      representative of bed sheets are analyzed. Since it is common practice in the
      manufacture of bed sheeting to use different types of yarn in the warp and weft
      direction to reduce cost, custom weaves were made from yarns produced by each of
      the three most common staple yarn production techniques to control this variable.
      It was found that porcine blood wicked into the fabrics made with ring spun yarn,
      but not into those made with open end or vortex spun yarns. The uneven wicking of
      blood into the different yarns resulted in elliptical-shaped stains on commercial
      bed sheeting that can be misleading when performing bloodstain pattern
      interpretation based on the stain morphology. This surprising result demonstrates
      that it is not sufficient to analyze the structure of the fabric, but one must
      also characterize the yarns from which the fabric is made. This study highlights
      the importance of a deeper characterization of the textile structure, even down
      to the yarn level, for BPA on textiles.

PMID- 28499151
TI  - Biphenyl based stationary phases for improved selectivity in complex steroid
      assays.
AB  - The measurement of steroid hormones and their corticoid precursors is an
      important aspect in endocrinology since these analytes are biomarkers for several
      endocrine disorders. Over the last few years, HPLC-MS/MS has become the method of
      choice to analyze these compounds. There are already several methods using
      stationary phases modified with C18 groups. However, since these columns
      sometimes do not enable sufficient separation of some isobaric steroids, we
      investigated the potential of a different RP modification using biphenyl groups
      for the separation of challenging isobars such as corticosterone, 11- and 21
      deoxycortisol. The aim of our work was the development of an isotope dilution
      UHPLC-MS/MS assay for clinical research that combines simple and effective sample
      preparation with a powerful MS method quantifying a broad steroid panel
      (aldosterone, corticosterone, cortisol, cortisone, 11-deoxycorticosterone, 11
      deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone, dehydroepiandrosterone
      sulfate, 17-OH-progesterone, progesterone, and testosterone) in human serum.
      After a manual protein precipitation step using zinc trifluoroacetate (ZnTFA) in
      methanol, the supernatants were directly injected into the UHPLC-MS system.
      Chromatographic baseline separation of all isobaric compounds (corticosterone<
      >11-deoxycortisol<->21-deoxycortisol, 17-OH-progesterone<->11
      deoxycorticosterone, and aldosterone<->cortisone) was achieved using a Kinetex
      Biphenyl column (150*2.1mm, 1.7MUm) with a mobile phase consisting of 0.2mM
      ammonium fluoride in water and methanol. The total run time was 10min. For
      detection we used a Xevo TQ-S mass spectrometer operating in the ESI positive and
      negative modes. The method was validated according to the EMA guideline for
      bioanalytical method validation. The results for accuracy (within-run: 92.3%
      115%, between-run: 92.4 %-113%) and imprecision (within-run: 0.80%-9.05%, between
      run: 1.98 %-15.2%) were satisfying. The recovery ranged from 95% to 111%. The
      matrix effect was between 93% and 112% and an excellent linearity with R2>0.99
      for all analytes was achieved. It was demonstrated that biphenyl based columns
      are a powerful tool for comprehensive, MS based steroid assays including various
      isobaric substances. Additionally, we could evince that ZnTFA is a convenient
      precipitation agent suitable for steroid analysis.

PMID- 28499152
TI  - Development of assay for determination of eletriptan hydrobromide in loaded PLGA
      nanoparticles.
AB  - Eletriptan Hydrobromide is a serotonin 5-HT1 receptor agonist and it used for the
      treatment of migraine headaches with or without aura. Even if the drug is well
      absorbed after oral administration, it has some drawbacks like first pass
      metabolism and decrease in bioavailability after migraine attacks. Encapsulation
      of drug into polymeric nanoparticles is one of the methods for protecting the
      drug against degradation. The present work described a preparation of Eletriptan
      Hydrobromide loaded poly (d,l-lactide-co-glycolide) nanoparticles prepared using
      o/w single emulsion solvent evaporation method. In order to determine the factors
      affecting the physicochemical properties of the nanoparticles on the particle
      size of poly (d,l-lactide-co-glycolide) nanoparticles, D-Optimal design is used.
      Moreover, novel, simple, sensitive, selective, and fully validated
      chromatographic technique for the quantification of Eletriptan Hydrobromide from
      Eletriptan Hydrobromide loaded poly(d,l-lactide-co-glycolide) nanoparticles was
      developed. Poly(d,l-lactide-co-glycolide) concentration, sonication time and
      sonication energy were found as significant factors (p<0.05) on particle size of
      nanoparticles. Limit of detection and limit of quantification values were
      calculated as 0.28MUgmL-1and 0.86MUgmL-1, respectively.

PMID- 28499153
TI  - Safety and efficacy of warfarin in patients with moderate thrombocytopenia.
AB  - INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring
      anticoagulation are currently sub-optimally treated because of bleeding concerns.
      Guidance on anticoagulating such patients is currently lacking because of limited
      data on safety and efficacy of anticoagulation in such patients. METHODS: This
      retrospective study compared the incidence of bleeding and thrombosis in a cohort
      of warfarinized patients with sustained platelet counts below 100*109/L against a
      cohort with normal platelet counts (>140*109/L). Primary outcomes of safety and
      efficacy were determined by incidence rate ratios (IRR) of bleeding and
      thrombotic events. International normalized ratio (INR) and platelet counts
      during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS:
      137 thrombocytopenic patients (104,985 patient-exposure days) were compared
      against 939 normal patients (715,193 patient-exposure days). IRR of minor, major
      bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57
      5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively.
      Median INR and platelet count readings during minor and major bleeds were 3.60
      (IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99*109/L (IQR: 77.0-147.0*109/L)
      and 115*109/L (IQR: 107.5-169.5*109/L) respectively. CONCLUSION: Warfarinized
      thrombocytopenic patients are at higher risk of minor bleeding complications with
      a higher tendency for major bleeding but derive similar benefits against
      thrombotic events compared to normal patients. Bleeding events are associated
      with higher INRs. A narrow INR target with an upper limit below 2.5 together with
      closer anticoagulation monitoring may improve safety of patients.

PMID- 28499154
TI  - Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid beta
      protein precursor abolishes its anti-thrombotic properties in vivo.
AB  - INTRODUCTION: Kunitz proteinase inhibitor (KPI) domain-containing forms of the
      amyloid beta-protein precursor (AbetaPP) inhibit cerebral thrombosis. KPI domain
      lacking forms of AbetaPP are abundant in brain. Regions of AbetaPP other than the
      KPI domain may also be involved with regulating cerebral thrombosis. To determine
      the contribution of the KPI domain to the overall function of AbetaPP in
      regulating cerebral thrombosis we generated a reactive center mutant that was
      devoid of anti-thrombotic activity and studied its anti-thrombotic function in
      vitro and in vivo. METHODS: To determine the extent of KPI function of AbetaPP in
      regulating cerebral thrombosis we generated a recombinant reactive center KPIR13I
      mutant devoid of anti-thrombotic activity. The anti-proteolytic and anti
      coagulant properties of wild-type and R13I mutant KPI were investigated in vitro.
      Cerebral thrombosis of wild-type, AbetaPP knock out and AbetaPP/KPIR13I mutant
      mice was evaluated in experimental models of carotid artery thrombosis and
      intracerebral hemorrhage. RESULTS: Recombinant mutant KPIR13I domain was
      ineffective in the inhibition of pro-thrombotic proteinases and did not inhibit
      the clotting of plasma in vitro. AbetaPP/KPIR13I mutant mice were similarly
      deficient as AbetaPP knock out mice in regulating cerebral thrombosis in
      experimental models of carotid artery thrombosis and intracerebral hemorrhage.
      CONCLUSIONS: We demonstrate that the anti-thrombotic function of AbetaPP
      primarily resides in the KPI activity of the protein.

PMID- 28499155
TI  - Simple screening protocol for identification of potential mycoremediation tools
      for the elimination of polycyclic aromatic hydrocarbons and phenols from
      hyperalkalophile industrial effluents.
AB  - A number of fungal strains belonging to the ascomycota, basidiomycota and
      zygomycota genera were subjected to an in vitro screening regime to assess their
      ligninolytic activity potential, with a view to their potential use in
      mycoremediation-based strategies to remove phenolic compounds and polycyclic
      aromatic hydrocarbons (PAHs) from industrial wastewaters. All six basidiomycetes
      completely decolorized remazol brilliant blue R (RBBR), while also testing
      positive in both the guaiacol and gallic acid tests indicating good levels of
      lignolytic activity. All the fungi were capable of tolerating phenanthrene, benzo
      alpha- pyrene, phenol and p-chlorophenol in agar medium at levels of 10 ppm. Six
      of the fungal strains, Pseudogymnoascus sp., Aspergillus caesiellus, Trametes
      hirsuta IBB 450, Phanerochate chrysosporium ATCC 787, Pleurotus ostreatus MTCC
      1804 and Cadophora sp. produced both laccase and Mn peroxidase activity in the
      ranges of 200-560 U/L and 6-152 U/L, respectively, in liquid media under nitrogen
      limiting conditions. The levels of adsorption of the phenolic and PAHs were
      negligible with 99% biodegradation being observed in the case of benzo-alpha
      pyrene, phenol and p-chlorophenol. The aforementioned six fungal strains were
      also found to be able to effectively treat highly alkaline industrial wastewater
      (pH 12.4). When this wastewater was supplemented with 0.1 mM glucose, all of the
      tested fungi, apart from A. caesiellus, displayed the capacity to remove both the
      phenolic and PAH compounds. Based on their biodegradative capacity we found T.
      hirsuta IBB 450 and Pseudogymnoascus sp., to have the greatest potential for
      further use in mycoremediation based strategies to treat wastestreams containing
      phenolics and PAHs.

PMID- 28499156
TI  - Treatment of chemical cleaning wastewater and cost optimization by response
      surface methodology coupled nonlinear programming.
AB  - The real alkaline cleaning wastewater (ACW) was treated by a process consisting
      of neutralization, NaClO oxidation and aluminum sulfate (AS) coagulation, and a
      novel response surface methodology coupled nonlinear programming (RSM-NLP)
      approach was developed and used to optimize the oxidation-coagulation process
      under constraints of relevant discharge standards. Sulfuric acid neutralization
      effectively removed chemical oxygen demand (COD), surfactant alkylphenol
      ethoxylates (OP-10) and silicate at the optimum pH of 7.0, with efficiencies of
      62.3%, >82.7% and 94.2%, respectively. Coagulation and adsorption by colloidal
      hydrated silica formed during neutralization were the major removal mechanisms.
      NaClO oxidation achieved almost complete removal of COD, but was ineffective for
      the removal of surfactant OP-10. AS coagulation followed by oxidation can
      efficiently remove OP-10 with the formation of Si-O-Al compounds. The optimum
      conditions for COD <=100 mg/L were obtained at hypochlorite to COD molar ratio of
      2.25, pH of 10.0 and AS dosage of 0.65 g Al/L, with minimum cost of 9.58 $/m3
      ACW. This study shows that the integrative RSM-NLP approach could effectively
      optimize the oxidation-coagulation process, and is attractive for techno-economic
      optimization of systems with multiple factors and threshold requirements for
      response variables.

PMID- 28499157
TI  - Identify temporal trend of air temperature and its impact on forest stream flow
      in Lower Mississippi River Alluvial Valley using wavelet analysis.
AB  - Characterization of stream flow is essential to water resource management, water
      supply planning, environmental protection, and ecological restoration; while air
      temperature variation due to climate change can exacerbate stream flow and add
      instability to the flow. In this study, the wavelet analysis technique was
      employed to identify temporal trend of air temperature and its impact upon forest
      stream flows in Lower Mississippi River Alluvial Valley (LMRAV). Four surface
      water monitoring stations, which locate near the headwater areas with very few
      land use disturbances and the long-term data records (60-90 years) in the LMRAV,
      were selected to obtain stream discharge and air temperature data. The wavelet
      analysis showed that air temperature had an increasing temporal trend around its
      mean value during the past several decades in the LMRAV, whereas stream flow had
      a decreasing temporal trend around its average value at the same time period in
      the same region. Results of this study demonstrated that the climate in the LMRAV
      did get warmer as time elapsed and the streams were drier as a result of warmer
      air temperature. This study further revealed that the best way to estimate the
      temporal trends of air temperature and stream flow was to perform the wavelet
      transformation around their mean values.

PMID- 28499158
TI  - Multi-segmental movement patterns reflect juggling complexity and skill level.
AB  - The juggling action of six experts and six intermediates jugglers was recorded
      with a motion capture system and decomposed into its fundamental components
      through Principal Component Analysis. The aim was to quantify trends in movement
      dimensionality, multi-segmental patterns and rhythmicity as a function of
      proficiency level and task complexity. Dimensionality was quantified in terms of
      Residual Variance, while the Relative Amplitude was introduced to account for
      individual differences in movement components. We observed that: experience
      related modifications in multi-segmental actions exist, such as the progressive
      reduction of error-correction movements, especially in complex task condition.
      The systematic identification of motor patterns sensitive to the acquisition of
      specific experience could accelerate the learning process.

PMID- 28499159
TI  - Sensitivity of biomechanical outcomes to independent variations of hindfoot and
      forefoot stiffness in foot prostheses.
AB  - Many studies have reported the effects of different foot prostheses on gait, but
      most results cannot be generalized because the prostheses' properties are seldom
      reported. We varied hindfoot and forefoot stiffness in an experimental foot
      prosthesis, in increments of 15N/mm, and tested the parametric effects of these
      variations on treadmill walking in unilateral transtibial amputees, at speeds
      from 0.7 to 1.5m/s. We computed outcomes such as prosthesis energy return, center
      of mass (COM) mechanics, ground reaction forces, and joint mechanics, and
      computed their sensitivity to component stiffness. A stiffer hindfoot led to
      reduced prosthesis energy return, increased ground reaction force (GRF) loading
      rate, and greater stance-phase knee flexion and knee extensor moment. A stiffer
      forefoot resulted in reduced prosthetic-side ankle push-off and COM push-off
      work, and increased knee extension and knee flexor moment in late stance. The
      sensitivity parameters obtained from these tests may be useful in clinical
      prescription and further research into compensatory mechanisms of joint function.

PMID- 28499160
TI  - Predicting settling performance of ANAMMOX granular sludge based on fractal
      dimensions.
AB  - The settling performance of ANAMMOX granular sludge determines the biomass
      retention in reactors, and finally determines the potential reaction capacity. In
      this paper, Stokes equation was modified by fractal dimensions to describe the
      settling performance of ANAMMOX granular sludge. A new method was developed to
      obtain fractal dimensions, and a fractal settling model was established for
      ANAMMOX granular sludge. The fractal settling model was excellent with only a
      small deviation of 0.8% from the experimental data. Assuming normal distribution
      of all Feret diameters, 88% experimental data fell into the 90% confidence
      interval of settling velocities. Further assuming logarithmic normal
      distribution, 95% experimental data fell into the 90% confidence interval. The
      fractal settling model is helpful for the prediction of settling velocities of
      granular sludge and the optimization of bioreactor performance.

PMID- 28499161
TI  - Determination of the Henry's law constants of low-volatility compounds via the
      measured air-phase transfer coefficients.
AB  - Accurate Henry's law constants (H) are unavailable for the majority of organic
      pollutants, especially those having a low volatility. A novel kinetics-based
      experimental method is introduced to determine H for a wide range of low-H
      compounds. The method consists of measuring independently the water-to-air
      transfer coefficient (KL) and the associated air-phase transfer coefficient (kG)
      of a low-H chemical (solute) in water when KL ? kGH prevails according to the two
      film theory. The kG for a solute is obtained via a developed gas-dynamic equation
      that relates kG to the solute molecular weight and the solute-vapor escaping
      efficiency (beta) through a boundary air layer. The value of beta is only a
      function of the in situ air turbulence level, independent of the chemical
      species. Thus, the required beta for solutes can be estimated from the
      evaporative rates of pure volatile liquids under the same ambient setting. By
      relating the estimated kG with the measured KL of a low-H solute, the solute H is
      established. The H values of 45 low-H chemicals, including many complex
      pesticides, in the range of ~10-7 to ~10-3 have thus been determined. The
      accountability of the method is underscored by the consistency of the measured
      and credible literature H values for a number of the low-H compounds studied.

PMID- 28499162
TI  - Factors associated with medication adherence among patients with diabetes in the
      Middle East and North Africa region: A systematic mixed studies review.
AB  - Multiple systematic reviews were conducted investigating factors associated with
      medication adherence worldwide. However, investigations from the Middle East and
      North Africa (MENA) region were largely underrepresented in those reviews.
      Therefore, the objective of this systematic review is to identify the factors
      influencing medication adherence among patients with diabetes in the MENA region.
      A systematic literature search was conducted through Cochrane Library, EBSCO,
      EMBASE, Google Scholar, ISI Web of Science, PubMed, ScienceDirect, SCOPUS, and
      ProQuest. Studies were included if they determined factors associated with
      medication adherence among patients with diabetes within the MENA region. Quality
      was assessed using Crow Critical Appraisal Tool. Thirty primary studies from 10
      MENA countries were included. The factors associated with medication adherence
      were categorized into demographics-related; disease- and medication-related;
      perception, attitude and psychological feelings-related; and societal-related
      factors. Positively associated factors included knowledge about the disease and
      medications, regular follow-up visits, and patients' positive beliefs about
      effectiveness and motivations about medications, while negatively associated
      factors included forgetfulness, side effects, and polypharmacy. Factors
      associated with medication adherence among patients with diabetes in the MENA
      region are highly diverse. The identified factors can serve as potential targets
      for culturally-relevant interventions to improve medication adherence and overall
      health outcomes.

PMID- 28499163
TI  - The Diabetic Retinopathy Barometer Study: Global perspectives on access to and
      experiences of diabetic retinopathy screening and treatment.
AB  - AIM: To assess the level of awareness, prevention and treatment of Diabetic Eye
      Disease (DED) comprising Diabetic Retinopathy (DR) and Diabetic Macula Edema
      (DME) retinopathy among adults with diabetes and health professionals. METHODS:
      The Diabetic Retinopathy Barometer Study consisted of a qualitative study, which
      consisted of semi-structured interviews, and a quantitative study using online
      surveys for adults with diabetes and for health professionals. RESULTS: A total
      of 4340 adults with diabetes and 2329 health professionals participated in the
      surveys. Diabetic eye disease (DED) without macular edema (DME) was reported by
      19.5% of adults with diabetes and a further 7.6% reported that they had DME.
      Although 94% of adults with diabetes saw a health care professional for their
      diabetes, only 79% had ever had an eye examination for DED, and 23% had not had
      an eye examination in the last year. Moreover, 65% of the ophthalmologists
      surveyed reported that most patients presented when visual problems had already
      occurred. Overall, 62% of people with DED had received treatment. Of these, 74%
      had laser therapy, 29% surgery and 24% anti-VEGF therapy. CONCLUSION: Strategic
      investment is required to enhance patient education and professional training on
      the importance of regular eye examinations; and in providing accessible DR
      screening programmes and proactive treatments.

PMID- 28499164
TI  - Mechanical properties and antibiotic release characteristics of poly(methyl
      methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.
AB  - The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics
      on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based
      bone cements is investigated. The incorporation of MSNs to the bone cements
      (8.15wt%) shows no detrimental effects on the biomechanical properties of the
      freshly solidified bone cements. Importantly, there are no significant changes in
      the compression strength and bending modulus up to 6 months of aging in PBS
      buffer solution. The preserved mechanical properties of MSN-functionalized bone
      cements is attributed to the unchanged microstructures of the cements, as more
      than 96% of MSNs remains in the bone cement matrix to support the cement
      structures after 6 months of aging. In addition, the MSN-functionalized bone
      cements are able to increase the drug release of gentamicin (GTMC) significantly
      as compared with commercially available antibiotic-loaded bone cements. It can be
      attributed to the loaded nano-sized MSNs with uniform pore channels which build
      up an effective nano-network path enable the diffusion and extended release of
      GTMC. The combination of excellent mechanical properties and sustainable drug
      delivery efficiency demonstrates the potential applicability of MSN
      functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery
      infection.

PMID- 28499165
TI  - Preparing diopside nanoparticle scaffolds via space holder method: Simulation of
      the compressive strength and porosity.
AB  - In the present study, diopside nanopowders were prepared via mechanical milling
      with eggshell as the calcium source. The space holder method (compaction of
      ceramic powder and spacer) as one of the most important methods to produce
      ceramic/metal scaffolds was used to produce diopside scaffolds. For the first
      time, the effect of the spacer size on mechanical properties and porosity of the
      obtained scaffolds was experimentally discussed. According to the results
      obtained, the NaCl particles (as the spacer) with the size of 400-600um
      maintained their original spherical shape during the compaction and sintering
      processes. As a new work, the most important parameters including the spacer
      type, spacer concentration, spacer size, and applied pressure were considered,
      and their effects on mechanical properties and porosity of diopside scaffolds
      were simulated. Gene Expression Programming (GEP), as one of the most branches of
      the artificial intelligence, was used for simulation process. By using the GEP,
      two equations were introduced to predict the compressive strength and porosity of
      the obtained scaffolds with the lowest error values. The 3D diagrams extracted
      from the model were used to evaluate the combined effect of the process
      parameters on the compressive strength and porosity of the scaffolds. The GEP
      model presented in this work has a very low level of error and a high level of
      the squared regression for predicting the compressive strength and porosity of
      diopside scaffolds.

PMID- 28499166
TI  - Potential biodegradable Zn-Cu binary alloys developed for cardiovascular implant
      applications.
AB  - Binary Zn-Cu alloy system is developed as potential biodegradable materials for
      cardiovascular implant application. The microstructure, tensile properties, in
      vitro corrosion behavior, cytotoxicity and antibacterial property of as-extruded
      Zn-xCu (x=1, 2, 3, and 4wt%) alloys are investigated systematically. It shows
      that as Cu content increases more CuZn5 phase precipitates. After extrusion, the
      CuZn5 phases are broken and the grains of Zn-xCu alloys are refined. Tensile test
      shows that Cu addition could significantly improve the mechanical properties of
      Zn-xCu alloys. Particularly, the elongation of the Zn-4Cu reaches 50.6+/-2.8%,
      which could facilitate the micro-tubes processing for stent fabrication. The
      micro-tubes of 3mm in outer diameter and 0.2mm in thickness as well as vascular
      stents have been fabricated successfully using the Zn-Cu binary alloy. The
      degradation rates of Zn-xCu alloys in c-SBF solution are quite low, which vary
      from 22.1+/-4.7 to 33.0+/-1.0MUmyear-1. With increasing Cu concentration, the
      corrosion rates of the Zn-xCu alloys generally exhibit a little increase compared
      with pure Zn, which show no significant difference among Zn-xCu alloys. In vitro
      test shows that Zn-xCu alloys exhibit acceptable cytotoxicity to human
      endothelial cells and the antibacterial property (S. aureus) is perfect when Cu
      concentration is higher than 2wt%. Therefore, the newly developed Zn-xCu binary
      alloys could be promising candidates for biodegradable cardiovascular implant
      application due to their excellent combination of strength and ductility, low
      degradation rates, acceptable cytotoxicity and good antibacterial property.

PMID- 28499167
TI  - Electrochemical behavior of hemin binding with human centrin 3.
AB  - The electrochemical responses of human centrin 3 (HsCen3) binding with hemin were
      studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using
      glassy carbon electrodes (GCEs). In CV, the formal potential (E0') of hemin with
      the addition of HsCen3 shifted from -0.51 to -0.36V (versus saturated calomel
      electrode, SCE), indicating that a new species of hemin-HsCen3 had formed. Upon
      binding with HsCen3, the redox current of hemin in CV and DPV decreased
      significantly. Based on their titration curves, the association constant of
      HsCen3 with hemin was obtained with a logK of approximately 4, which was
      consistent with that obtained from spectroscopy. Combining UV-Vis, fluorescence
      emission, and electrochemical methods, His100 located on the alpha-helix between
      the two domains of HsCen3 was identified as the ligand binding residue of hemin.
      The protein binding-induced change in electrochemical signal was thus used to
      construct the diffusion coefficient (D=1.43*10-7cm2/s), the charge-transfer
      coefficient (alpha=0.49), and electron transfer standard rate constant
      (ks=2.54*10-2s-1) in the presence or absence of HsCen3. The electrochemical
      investigation of hemin bound with HsCen3 may provide useful data for
      understanding the biological processes of calcium-binding protein.

PMID- 28499168
TI  - Novel Imidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxides as antiproliferative
      trypanosoma cruzi drugs: Computational screening from neural network, synthesis
      and in vivo biological properties.
AB  - A new family of imidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxide with
      antiproliferative Trypanosoma cruzi properties was identified from a neural
      network model published by our group. The synthesis and evaluation of this new
      class of trypanocidal agents are described. These compounds inhibit the growth of
      Trypanosoma cruzi, comparable with benznidazole or nifurtimox. In vitro assays
      were performed to study their effects on the growth of the epimastigote form of
      the Tulahuen 2 strain, as well as the epimastigote and amastigote forms of CL
      clone B5 of Trypanosoma cruzi. To verify selectivity towards parasite cells, the
      non-specific cytotoxicity of the most relevant compounds was studied in mammalian
      cells, i.e. J774 murine macrophages and NCTC clone 929 fibroblasts. Furthermore,
      these compounds were assayed regarding the inhibition of cruzipain. In vivo
      studies revealed that one of the compounds, 19, showed interesting trypanocidal
      activity, and could be a very promising candidate for the treatment of Chagas
      disease.

PMID- 28499170
TI  - 4-Phenyl quinoline derivatives as potential serotonin receptor ligands with
      antiproliferative activity.
AB  - Antagonists of signaling receptors are often effective non-toxic therapeutic
      agents. Over the years, there have been evidences describing the role of
      serotonin or 5-hydroxytryptamine (5-HT) in development of cancer. Although there
      are reports on the antiproliferative effects of some serotonin receptor
      antagonists, there are very few investigations related to understanding their
      structure-activity relationships. In this study, we report the screening of a
      library of 4-phenyl quinoline derivatives for their antiproliferative activities.
      Preliminary docking studies indicated that these ligands had the ability to bind
      to two of the serotonin receptors, 5-HT1B and 5-HT2B. The results of the in
      silico experiments were validated by performing in vitro studies on MCF-7 breast
      cancer cell line. The ethylpiperazine derivatives showed maximum toxicity against
      this cancer cell line. The compounds inhibited Calcium ion efflux (induced by
      serotonin) and ERK activation. One of the most active 4-phenyl quinoline
      derivatives (H3a) also induced apoptosis, thereby, suggesting the use of this
      scaffold as a potential anticancer drug.

PMID- 28499169
TI  - Two novel dinuclear ellipsoid Ni(II) and Co(II) complexes bridged by 4,5
      bis(pyrazol-1-yl)phthalic acid: Synthesis, structural characterization and
      biological evaluation.
AB  - Two novel complexes, [Ni2(L)2(H2O)3].4(H2O) (1) and [Co2(L)2(H2O)3].5(H2O) (2)
      [H2L = 4,5-bis(pyrazol-1-yl) phthalic acid] were synthesized and characterized by
      spectroscopy (IR, 1H NMR), and elemental analysis. The structures for the
      complexes were determined by X-ray crystallography providing the dinuclear
      ellipsoid Ni(II) and Co(II) complexes bridged by 4,5-bis(pyrazol-1-yl)phthalic
      acid ligands with same coordination modes. The interaction capacity of the
      complexes with FS-DNA (fish sperm DNA) has been investigated by UV and
      fluorescence spectroscopy. Gel electrophoresis assay demonstrated the ability of
      the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the
      complexes was tested against two different cancer cell lines, HeLa (human cervix
      epithelia carcinoma cells) and KB (human oral epithelial carcinoma cells),
      exhibiting significant cancer cell inhibitory rate. Furthermore, flow cytometry
      experiments and morphological apoptosis studies showed that the complexes induced
      apoptosis of KB tumor cell lines. The good visualization images supported with
      the experimental results of structure-activity relationship.

PMID- 28499171
TI  - Quinazoline based alpha1-adrenoreceptor antagonists with potent antiproliferative
      activity in human prostate cancer cell lines.
AB  - New alpha1-adrenoreceptor (alpha1-AR) antagonists related to prazosin and
      doxazosin were synthesized by replacing piperazine ring with (S)- or (R)-3
      aminopiperidine. Binding studies indicated that the S configuration at the 3-C
      position of the piperidine ring is crucial for an optimal interaction of the
      compounds at all three alpha1-AR subtypes. Quinazolines 9 and 10, bearing a
      quinone ring on the lateral chain, exhibited also potent antiproliferative
      activity in LNCaP androgen-sensitive prostate cancer cell lines, higher than that
      of doxazosin. Compound 10 increased apoptosis, in terms of DNA fragmentation,
      without triggering cell necrosis. The prooxidant activity found in compound 10
      may underlie its ability to inhibit cell proliferation in synergy with the effect
      mediated by alpha1-AR antagonism. Due to its better biological profile compared
      to doxazosin for LNCaP cell line, compound 10 might be a valuable lead compound
      for the design of new prostate antitumor agents.

PMID- 28499172
TI  - Fluorescence quenching study on the interaction of ferroferric oxide
      nanoparticles with bovine serum albumin.
AB  - Fluorescence quenching was used to study the potential interaction mechanism of
      Bovine serum albumin (BSA) with either hydrophilic ferroferric oxide (Fe3O4)
      nanoparticles (NPs) or hydrophobic Fe3O4 NPs. The experimental results indicated
      the mechanism between BSA and hydrophilic Fe3O4 NPs was static quenching and the
      one between BSA and hydrophobic Fe3O4 NPs was dynamic process that was drove by
      Forster's resonance energy transfer (FRET). And the binding parameters for the
      interaction of BSA with either hydrophilic or hydrophobic Fe3O4 NPs were
      calculated by using the fluorescence quenching measurement. The binding constant
      (KA) values of hydrophilic Fe3O4 NPs were 8518.73+/-23.35 (at 298K), 1190.31+/
      15.41 (at 306K) and 321.97+/-8.57 (at 313K), respectively. The thermodynamic
      analysis implied that the intermolecular forces between BSA and hydrophilic Fe3O4
      NPs were Van der Waals interaction or hydrogen bond, because the values of DeltaH
      and DeltaS between them were negative. While the one of BSA and hydrophobic Fe3O4
      NPs involved hydrophobic forces, owing to the positive DeltaH and DeltaS between
      them. But they were all enthalpy-driven and exothermic, since their DeltaG values
      were all negative. Synchronous fluorescence spectroscopy suggested that the
      conformation of tryptophan residue of BSA was changed in the presence of
      hydrophilic Fe3O4 NPs or hydrophobic Fe3O4 NPs, because the position of the
      maximum emission wavelength had a discernible red shift.

PMID- 28499173
TI  - Combination photodynamic therapy of human breast cancer using salicylic acid and
      methylene blue.
AB  - The objective of this study was to evaluate the effects of combination therapy
      with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid
      (SA) as chemo-therapy anticancer agent. The binding of salicylic acid to
      methylene blue was studied using spectrophotometric method. The results show the
      1:2 complex formation between SA and MB. The binding constants and related Gibbs
      free energies o are obtained (Kb1=183.74, Kb2=38.13 and ?Gb1 degrees =12.92kJ.mol
      1, ?Gb2 degrees =9.02kJ.mol-1). The spectrophotometric results show the
      improvement in solubilization and reduction prevention for SA and MB in the
      complex form. These results are in agreements with cellular experiments. The dark
      toxicity measurements represent the improve efficacy of chemotherapy using
      combination of SA and MB. The photodynamic therapy results (using red LED as
      light source (630nm; power density: 30mWcm-2)) show that the cancer cell killing
      efficiency of MB increases in the combination with SA due to reduction prevention
      and stabilization of monomeric form of MB.

PMID- 28499174
TI  - Interaction between triethanolamine and singlet or triplet excited state of
      xanthene dyes in aqueous solution.
AB  - Triethanolamine (TEOA) has been often used as a hole-scavenger in dye-sensitized
      semiconductor photocatalytic systems. However, the femtosecond time-resolved
      kinetics of the interaction between a sensitized dye and TEOA has not been
      reported in literatures. Herein, we selected four commonly used xanthene dyes,
      such as fluorescein, dibromofluorescein, eosin Y, and erythrosine B, and studied
      their ultrafast fluorescence quenching dynamics in the presence of TEOA in
      aqueous solution, respectively, by using both femtosecond transient absorption
      and time-resolved fluorescence measurements. We obtained the electron transfer
      rate from TEOA to each photoexcited xanthene dye in 2.0 M TEOA solution. We also
      obtained the intersystem crossing rate of each xanthene dye in aqueous solution
      with fluorescence quantum yield and lifetime measurements. Finally we found that
      TEOA mainly interacts with the singlet excited-state of fluorescein,
      dibromofluorescein, and eosin Y, and that TEOA can interact with both the singlet
      and triplet excited-states of erythrosine B in high concentration of TEOA aqueous
      solution.

PMID- 28499175
TI  - Vibrational spectroscopic and computational studies on diisopropylammonium
      bromide.
AB  - Diisopropylammonium bromide (DIPAB) can be crystallized either in an orthorhombic
      (P212121) or in a monoclinic (P21) structure at room temperature depending on
      synthesis conditions. The non-polar orthorhombic structure exhibits a subtle,
      irreversible transformation into the ferroelectric monoclinic-II (m-II) phase
      above ~421K. At a slightly higher temperature of 426K this m-II (P21) phase
      reversibly transforms into a disordered, paraelectric monoclinic-I (P21/m)
      structure. We synthesized DIPAB in the orthorhombic structure, heated it to
      obtain the m-II phase and carried out a systematic study of their Raman and IR
      spectra. We obtained the phonon irreducible representations from factor group
      analysis of the orthorhombic and m-II structures based on the reported structural
      information. DIPAB is an organic molecular crystal, and the vibrational spectra
      in the intramolecular region (200-3500cm-1) of the two different phases are
      identical to each other, indicating weak inter-molecular interactions in both
      crystalline structures. In the low wavenumber region (10-150cm-1) the Raman
      spectra of the two phases are different due to their sensitivity to molecular
      environment. We also carried out first principles calculations using Gaussian 09
      and CASTEP codes to analyze the vibrational frequencies. Mode assignments were
      facilitated by isolated molecule calculations that are also in good agreement
      with intramolecular vibrations, whereas CASTEP (solid state) results could
      explain the external modes.

PMID- 28499176
TI  - Brain networks, structural realism, and local approaches to the scientific
      realism debate.
AB  - We examine recent work in cognitive neuroscience that investigates brain
      networks. Brain networks are characterized by the ways in which brain regions are
      functionally and anatomically connected to one another. Cognitive neuroscientists
      use various noninvasive techniques (e.g., fMRI) to investigate these networks.
      They represent them formally as graphs. And they use various graph theoretic
      techniques to analyze them further. We distinguish between knowledge of the graph
      theoretic structure of such networks (structural knowledge) and knowledge of what
      instantiates that structure (nonstructural knowledge). And we argue that this
      work provides structural knowledge of brain networks. We explore the significance
      of this conclusion for the scientific realism debate. We argue that our
      conclusion should not be understood as an instance of a global structural realist
      claim regarding the structure of the unobservable part of the world, but instead,
      as a local structural realist attitude towards brain networks in particular. And
      we argue that various local approaches to the realism debate, i.e., approaches
      that restrict realist commitments to particular theories and/or entities, are
      problematic insofar as they don't allow for the possibility of such a local
      structural realist attitude.

PMID- 28499177
TI  - The dechlorination of pentachlorophenol under a sulfate and iron reduction co
      occurring anaerobic environment.
AB  - An anaerobic soil slurry incubation experiment was conducted by controlling
      different Fe/S mole ratios (1/3, 1/2, 1/1, 2/1, 3/1, 8/1 and the control without
      sulfate) through the addition of sodium sulfate, to investigate the effect of
      sulfate and iron reduction on the reductive dechlorination of pentachlorophenol
      (PCP). Two sequential incubation periods were carried out with the stage I
      incubation conducted under a low electron donor concentration (0.5 mM lactate)
      and stage II incubation conducted under increased electron donor supply with
      lactate at 20 mM. During stage I, the production of Fe(II) occurred markedly
      while sulfate reduction and PCP dechlorination rate were low, with the highest
      dechlorination rates of PCP only 11.0% among all treatments at the end of stage I
      incubation. During stage II, both PCP dechlorination and sulfate reduction were
      greatly enhanced in all treatments, while the concentration of Fe(II) changed
      slightly. The rate of PCP dechlorination decreased (from 87.7% to 34.2%) with the
      increase of sulfate concentration (from Fe/S mole ratio of 8/1 to 1/3). Our study
      suggested that the presence of a certain amount of sulfate might facilitate PCP
      dechlorination in the range of Fe/S mole ratios greater than 1 when compared with
      the control without SO42-. With the investigation of the dechlorination of PCP
      under the Fe-S-PCP coexisting condition with different Fe/S mole ratios, our
      study may provide improved strategy for optimizing the remediation of flooded
      soils and sediments polluted by PCP.

PMID- 28499178
TI  - Degradation of gaseous formaldehyde via visible light photocatalysis using multi
      element doped titania nanoparticles.
AB  - This study developed a modified titanium dioxide photocatalyst doped with multi
      element synthesized via sol-gel process to productize a novel photocatalyst. The
      study includes degradation of gaseous formaldehyde under visible light using the
      synthesized novel titanium dioxide photocatalyst. Varying molar ratios from 0 to
      2 percent (%mole in titanium dioxide) of ammonium fluoride, silver nitrate and
      sodium tungstate as dopant precursors for nitrogen, fluorine, silver and tungsten
      were used. Photodegradation of gaseous formaldehyde was examined on glass tubular
      reactors illuminated with blue light emitting diodes (LEDs) using immobilized
      photocatalyst. The photocatalytic yield is analyzed based on the photocatalyst
      surface chemical properties via X-ray Photoelectron Spectroscopy (XPS), Fourier
      Transform Infrared (FTIR) Spectrophotometry, Brunauer-Emmett-Teller (BET) and X
      ray Diffraction (XRD) characterization results. The applied modifications
      enhanced the visible light capability of the catalyst in comparison to the
      undoped catalyst and commercially available Degussa P-25, such that it
      photocatalytically degrades 88.1% of formaldehyde in 120 min. Synthesized
      titanium dioxide photocatalyst exhibits a unique spin orbital at 532.07 eV and
      533.27 eV that came from the hybridization of unoccupied Ti d(t2g) levels.

PMID- 28499179
TI  - Fluorescent natural organic matter responsible for ultrafiltration membrane
      fouling: Fate, contributions and fouling mechanisms.
AB  - Membrane fouling has been a main obstacle to the success of ultrafiltration (UF)
      technology. Recently, fluorescent natural organic matter (FNOM), including humic
      like substances (HS) and protein-like substances, has been recognized as
      substances responsible for membrane fouling. In this study, the matrix of FNOM in
      natural river water was substantially modified by combined coagulation and
      powdered activated carbon adsorption to enhance the diversity of the FNOM matrix.
      Fluorescence excitation emission matrix spectroscopy was employed to characterize
      FNOM components during the UF process. The correlations between FNOM components
      of the feedwater and membrane fouling were evaluated for the initial period and
      long-term operation. Reliable correlations of the maximum fluorescence intensity
      of HS with initial membrane fouling indicated that HS were major foulants in the
      initial period. Furthermore, the protein-like component exhibited significant
      correlation with the concentration effect fouling (R2 = 0.6131) and with
      irreversible fouling (R2 = 0.8711). We found that the fouling mechanism changed
      from pore obstruction to a protein concentration polarization layer followed by
      protein cake layer filtration. Total fouling of the UF membrane over long-term
      operation was alleviated with powdered activated carbon (PAC) adsorption;
      however, the mitigation of irreversible fouling was dependent on whether PAC
      adsorbed protein-like substances.

PMID- 28499180
TI  - Bioremediation of phenol in soil through using a mobile plant-endophyte system.
AB  - Plant-endophyte remediation of volatile pollutants in soil is an emerging
      technology. For more efficient application, plant-endophyte systems were formed
      through stimulation of transfer of degradative plasmids in plant tissue by co
      inoculation of corn, wheat or tomato seedlings with Pseudomonas fluorescens TP13
      carrying a self-transmissible degradative plasmid, and P. fluorescens
      streptomycin-resistant P13 strain. The corn-TP13-P13 (CTP) system had higher
      degradation activity than other plant-endophyte systems. Transplanting the CTP,
      from loam to sandy clay loam soil, from greenhouse to field trials, almost
      completely removed phenol from contaminated soils in 15 d. Intact transplantation
      of the CTP to contaminated soils was more efficient than co-transplanting of
      phenol-degrading bacteria and plant in detoxification of phenol. After the
      experiments the harvested CPT still exhibited remarkable bioremediation activity.
      The number of degradative plasmid-carrying endophytic bacteria in the CTP system
      was just slightly more than in the corn seedlings inoculated with TP13 alone, but
      the former substantially surpassed the latter in phenol-degrading activity,
      probably due to stimulation of transfer of the degradative plasmids among
      endophytic bacteria in plant tissues. More degradative plasmid-carrying bacteria
      colonized bioremediating soil and plant tissues, and higher plasmid transfer
      frequency and C23O activity of transconjugant were found in soils for the CTP
      system compared with other treatments. These results showed that the CTP system
      is a valuable tool to degrade volatile organic pollutants and transfer of
      degradative plasmids in plant tissues is important for construction of a mobile
      plant-endophyte system applied in bioremediation of volatile pollutants.

PMID- 28499181
TI  - Influence of temperature and pH on the anammox process: A review and meta
      analysis.
AB  - The anammox (anaerobic ammonium oxidation) process was considered a very
      efficient and economic wastewater treatment technology immediately after its
      discovery in 1995, thus research in this field was intensified. The anammox
      process is characterised by a high temperature optimum and is very sensitive to
      both temperature and pH fluctuations. The process can also be inhibited by many
      factors, including by its substrates, i.e. nitrite and ammonium (or its unionised
      forms: free ammonia and free nitrous acid). This paper presents a comprehensive
      study of the most important and recent findings on the influence of two
      parameters that are crucial in wastewater treatment, i.e. temperature and pH.
      Because both parameters may influence the anammox process simultaneously, a meta
      analysis was conducted of the data from the literature. Although meta-analysis is
      commonly used in medical research, mathematical analysis of the literature data
      has become an interesting and important step in the environmental sciences. This
      paper presents information on the influence of both temperature and pH on process
      efficiency and microbial composition. Additionally, the responses of different
      operating systems on both temperature and pH changes are described. Moreover, the
      role of both adaptation to changed conditions and of pH control as well as
      indicated areas of process operation are discussed.

PMID- 28499182
TI  - Perfluorooctane sulfonate adsorption on powder activated carbon: Effect of
      phosphate (P) competition, pH, and temperature.
AB  - Powdered activated carbon (PAC), as an adsorbent, was applied to remove
      perfluorooctane sulfonate (PFOS) from aqueous solution. Laboratory batch
      experiments were performed to investigate the influences of phosphate (P)
      competition, temperature, and pH for PFOS adsorption onto PAC. The results showed
      that higher temperature favored PFOS adsorption in single and binary systems. The
      kinetic data fitted very well to the pseudo second-order kinetic model.
      Thermodynamically, the endothermic enthalpy of the PFOS adsorption in single and
      binary systems were 125.07 and 21.25 kJ mol-1, respectively. The entropy of the
      PFOS adsorption in single and binary systems were 0.479 and 0.092 kJ mol-1 K-1,
      respectively. And the Gibbs constants were negative. These results indicated that
      the adsorption processes were spontaneous. The adsorption isotherms of PFOS
      agreed well with the Langmuir model. In the single system, PFOS adsorption
      decreased with increased pH value. The difference in the amount of PFOS
      adsorption between the single and binary systems increased at higher pH.
      Frustrated total internal reflection (FTIR) demonstrated that P competition
      increased the hydrophilicity of the PAC and the electrostatic repulsion between
      PFOS and PAC, then the PFOS adsorption amount decreased. It also demonstrated
      that, at higher temperature, increased PFOS adsorption was mainly due to the
      higher diffusion rate of PFOS molecules and greater number of active sites opened
      on the PAC surface.

PMID- 28499183
TI  - Contribution of filamentous fungi to the musty odorant 2,4,6-trichloroanisole in
      water supply reservoirs and associated drinking water treatment plants.
AB  - In this study, the distribution of 2,4,6-trichloroanisole (2,4,6-TCA) in two
      water supply reservoirs and four associated drinking water treatment plants
      (DWTPs) were investigated. The 2,4,6-TCA concentrations were in the range of 1.53
      2.36 ng L-1 in water supply reservoirs and 0.76-6.58 ng L-1 at DWTPs. To
      determine the contribution of filamentous fungi to 2,4,6-TCA in a full-scale
      treatment process, the concentrations of 2,4,6-TCA in raw water, settled water,
      post-filtration water, and finished water were measured. The results showed that
      2,4,6-TCA levels continuously increased until chlorination, suggesting that 2,4,6
      TCA could form without a chlorination reaction and fungi might be the major
      contributor to the 2,4,6-TCA formation. Meanwhile, twenty-nine fungal strains
      were isolated and identified by morphological and molecular biological methods.
      Of the seventeen isolated fungal species, eleven showed the capability to convert
      2,4,6-trichlorophenol (2,4,6-TCP) to 2,4,6-TCA. The highest level of 2,4,6-TCA
      formation was carried out by Aspergillus versicolor voucher BJ1-3: 40.5% of the
      original 2,4,6-TCP was converted to 2,4,6-TCA. There was a significant variation
      in the capability of different species to generate 2,4,6-TCA. The results from
      the proportions of cell-free, cell-attached, and cell-bound 2,4,6-TCA suggested
      that 2,4,6-TCA generated by fungi was mainly distributed in their extracellular
      environment. In addition to 2,4,6-TCA, five putative volatile by-products were
      also identified by gas chromatography and mass spectrometry. These findings
      increase our understanding on the mechanisms involved in the formation of 2,4,6
      TCA and provide insights into managing and controlling 2,4,6-TCA-related problems
      in drinking water.

PMID- 28499184
TI  - Effects of graphite nanoparticles on nitrification in an activated sludge system.
AB  - Graphite nanoparticles (GNPs) might result in unexpected effects during their
      transportation and transformation in wastewater treatment systems, including
      strong thermo-catalytic and catalytic effects and microbial cytotoxicity. In
      particular, the effects of GNPs on the nitrification process in activated sludge
      systems should be addressed. This study aimed to estimate the influence of GNPs
      on the nitrification process in a short-term nitrification reactor with exposure
      to different light sources. The results indicated that GNPs could only improve
      the efficiency of photothermal transformation slightly in the activated sludge
      system because of its photothermal effects under the standard illuminant
      (imitating 1 * sun). However, even with better photothermal effects, the
      nitrification efficiency still decreased significantly with GNP dosing under the
      standard illuminant, which might result from stronger cytotoxic effects of GNPs
      on the nitrifying bacteria. The disappearance of extracellular polymeric
      substances (EPS) around bacterial cells was observed, and the total quantity of
      viable bacteria decreased significantly after GNP exposuring. Variation in
      bacterial groups primarily occurred in nitrifying microbial communities,
      including Nitrosomonas sp., Nitrosospira sp., Comamonas sp. and Bradyrhizobiace
      sp. Nitrifiers significantly decreased, while the phyla Gammaproteobacteria,
      Deinocccus, and Bacteroidetes exhibited greater stability during GNP treatment.

PMID- 28499185
TI  - Prevalence and profile of Neurodevelopment and Fetal Alcohol Spectrum Disorder
      (FASD) amongst Australian Aboriginal children living in remote communities.
AB  - BACKGROUND: Despite multiple risk factors for neurodevelopmental vulnerability,
      few studies have assessed neurodevelopmental performance of Australian Aboriginal
      children. An important risk factor for neurodevelopmental vulnerability is
      prenatal alcohol exposure (PAE), which places children at risk for Fetal Alcohol
      Spectrum Disorder (FASD). AIMS: This study assesses neurodevelopment outcomes in
      a population of Australian Aboriginal children with and without PAE. METHODS AND
      PROCEDURES: Children born in 2002/2003, and living in the Fitzroy Valley, Western
      Australia between April 2010 and November 2011, were eligible (N=134).
      Sociodemographic and antenatal data, including PAE, were collected by interview
      with 127/134 (95%) consenting parents/caregivers. Maternal/child medical records
      were reviewed. Neurodevelopment was assessed by clinicians blinded to PAE in
      108/134 (81%) children and diagnoses on the FASD spectrum were assigned. OUTCOMES
      AND RESULTS: Neurodevelopmental disorder was documented in 34/108 children (314.8
      per 1000). Any diagnosis on the FASD spectrum was made in 21/108 (194.4 per 1000)
      children (95% CI=131.0-279.0). CONCLUSIONS AND IMPLICATIONS: Neurodevelopmental
      impairment with or without PAE is highly prevalent among children in the Fitzroy
      Valley. Rates of diagnoses on the FASD spectrum are among the highest worldwide.
      Early intervention services are needed to support developmentally vulnerable
      children in remote communities.

PMID- 28499186
TI  - Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3
      inflammasome.
AB  - In the present study, we attempted to elucidate whether molecular modulation of
      inflammation by betaine through the forkhead box O1 (FOXO1)-induced NLRP3
      inflammasome improves insulin resistance. Betaine is a major water-soluble
      component of Lycium chinense. It mainly functions as an oxidative metabolite of
      choline by suppressing superoxide-induced free radicals by donating methyl
      groups. The FOXO1 transcription factor regulates various genes involved in
      cellular metabolic processes related to cell death as well as oxidative stress
      responses through binding to the thioredoxin-interacting protein (TXNIP). Betaine
      is known to inhibit FOXO1 phosphorylation through phosphoinositide 3-kinase
      (PI3K)/protein kinase B (AKT) in liver cells exposed to insulin. To elucidate the
      molecular mechanism of inactivation of insulin-induced FOXO1 by the antioxidant
      betaine, we used HepG2 cells and the liver of db/db mice treated with betaine at
      a dose of 50 mg/kg/day for 3 weeks. We found that the activation of NLRP3
      inflammasome genes was reduced by betaine, which resulted in the suppression of
      reactive species (RS) production in liver cells. In addition, betaine inhibited
      insulin-induced PI3K/AKT and FOXO1 activation. Therefore, betaine suppressed the
      cytokine interleukin-1beta production by inhibiting the activation of the NLRP3
      inflammasome via interaction of FOXO1 and TXNIP. Our results suggest that betaine
      inhibits the FOXO1 binding to TXNIP, leading to the suppression of RS-induced
      NLRP3 inflammasome activation in a diabetic liver.

PMID- 28499187
TI  - Vortioxetine: A review of the pharmacology and clinical profile of the novel
      antidepressant.
AB  - The aim of this paper was to review the up-to-date evidence base on pharmacology
      and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant,
      approved by the US Food and Drug Administration (FDA) for the treatment of major
      depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant
      and anxiolytic effect, it may be effective in treating both depressive and
      anxiety disorders, such as generalized anxiety disorder (GAD). Based on its
      pharmacodynamics profile and preclinical studies, it is believe that the drug's
      clinical action is mediated mainly by selective blockade of serotonin reuptake
      (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT
      receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B). In patients with
      MDD the recommended doses range is 5-20mg/day. Vortioxetine was shown to be more
      effective than placebo both in MDD and GAD. In terms of side effects, nausea,
      vomiting, diarrhea, and dry mouth were most commonly observed in individuals
      receiving vortioxetine. In direct comparison to duloxetine, vortioxetine is found
      to have a smaller efficacy but had a lower risk of developing the common
      antidepressant-induced adverse effects.

PMID- 28499188
TI  - PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their kinetic
      properties and molecular docking simulation.
AB  - Diabetes is one of the most popular worldwide diseases, regulated by the defects
      in insulin secretion, insulin action, or both. The overexpression of protein
      tyrosine phosphatase 1B (PTP1B) was found to down-regulate the insulin-receptor
      activation. PTP1B has been known as a strategy for the treatment of diabetes via
      the regulation of insulin signal transduction pathway. Herein, we investigated
      the PTP1B inhibitors isolated from natural sources. The chemical investigation of
      Selaginella tamariscina (Beauv.) Spring revealed seven unsaturated alkynyl
      phenols 1-7, four new selaginellins T-W 1-4 together with three known compounds 5
      7 isolated from the aerial parts. The structures of the isolates were determined
      by spectroscopic techniques (1D/2D-NMR, MS, and CD). The inhibitory effects of
      these isolates on the PTP1B enzyme activity were investigated. Among them,
      compounds 2-7 significantly exhibited the inhibitory effects with the IC50 values
      ranging from 4.8 to 15.9MUM. Compound 1 moderately displayed the inhibitory
      activity with an IC50 of 57.9MUM. Furthermore, active compounds were discovered
      from their kinetic and molecular docking analysis. The results revealed that
      compounds 2 and 4-7 were mixed-competitive inhibitors, whereas compound 3 was a
      non-competitive inhibitor. This data confirm that these compounds exhibited
      potential inhibitory effect on the PTP1B enzyme activity.

PMID- 28499189
TI  - Synthesis, biological evaluation and molecular modeling study of new (1,2,4
      triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3H)-one as
      DHFR inhibitors.
AB  - A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized
      and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial
      activity. Compound 17 proved to be the most active DHFR inhibitor with IC50 value
      of 0.01MUM, eight fold more active than methotrexate (MTX). Compounds 16 and 24
      showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell
      lines with IC50 values of 25.4 and 9.5MUg/ml, respectively. Compounds 15, 20, 21
      and 30 showed considerable activity against the Gram-positive bacteria
      Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis
      with a magnitude of potency comparable to the broad spectrum antibiotic
      Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against
      Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular
      docking mode with MTX and made a critical hydrogen bond and arene-arene
      interactions via Ala9 and Phe34 amino acid residues, respectively.

PMID- 28499190
TI  - Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their
      protein tyrosine phosphatase and acetylcholinesterase inhibitory activities.
AB  - A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and
      another flavone glycoside with spectroscopic data reported for the first time,
      kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1->6)]-beta-d-glucoside (3),
      along with 16 known compounds were isolated from the aerial parts of Agrimonia
      pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among
      them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B
      with IC50 values of 7.14+/-1.75 and 7.73+/-0.24MUM, respectively. In addition,
      compound 1 showed significant inhibitory effect with an IC50 value of 17.03+/
      0.09MUM. Furthermore, these compounds were tested in AChE inhibitory assays. Most
      of them were found to have moderate inhibitory effects, with IC50 values ranging
      from 60.20+/-1.09 to 92.85+/-1.12MUM. Except compounds 3, 8, and 18 were
      inactive.

PMID- 28499191
TI  - Spatiotemporal signal classification via principal components of reservoir
      states.
AB  - Reservoir computing is a recently introduced machine learning paradigm that has
      been shown to be well-suited for the processing of spatiotemporal data. Rather
      than training the network node connections and weights via backpropagation in
      traditional recurrent neural networks, reservoirs instead have fixed connections
      and weights among the 'hidden layer' nodes, and traditionally only the weights to
      the output layer of neurons are trained using linear regression. We claim that
      for signal classification tasks one may forgo the weight training step entirely
      and instead use a simple supervised clustering method based upon principal
      components of reservoir states. The proposed method is mathematically analyzed
      and explored through numerical experiments on real-world data. The examples
      demonstrate that the proposed may outperform the traditional trained output
      weight approach in terms of classification accuracy.

PMID- 28499192
TI  - Handgrip strength is associated with anthropometrics variables and sex in
      preschool children: A cross sectional study providing reference values.
AB  - OBJECTIVE: The purpose of this study was to examine the influence of age, sex and
      anthropometric variables in handgrip strength and to determine norm-referenced
      values for preschool children. DESIGN: Cross-sectional study. SETTING: Schools.
      PARTICIPANTS: A total of 1215 children, aged 3-6 years (590 girls and 625 boys).
      INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Handgrip strength (HS),
      measured by the CAMRY hydraulic hand dynamometer (EH101; Camry, Guangdong
      Province, China). RESULTS: Boys exhibited a greater performance than girls in the
      4 and 5 years age groups, but no significant differences were found at 3 and 6
      years. In relation to growth, HS performance was greater with increased age. The
      Pearson correlation analysis showed significant correlations between HS and body
      mass (r = 0.354, p < 0.001), body height (r = 0.352, p < 0.001), body mass index
      (r = 0.164, p < 0.001) and waist circumference (r = 0.118, p < 0.001).
      CONCLUSION: This study provides references values for muscular strength
      assessment by an HS test carried out on a large sample of preschoolers in
      relation to age and sex. Additionally, some differences in HS performance were
      found according to sex.

PMID- 28499193
TI  - Stachydrine ameliorates isoproterenol-induced cardiac hypertrophy and fibrosis by
      suppressing inflammation and oxidative stress through inhibiting NF-kappaB and
      JAK/STAT signaling pathways in rats.
AB  - Cardiac hypertrophy (CH), as one of the major causes of morbidity and mortality
      in the world, has become an independent and predictive risk factor for adverse
      cardiovascular events. However, progress in treatment remains sluggish in recent
      years. Therefore, compounds derived from non-toxic nature plants are urgently
      needed. Stachydrine (STA), which is isolated from Leonurus, has various
      activities, including resistance to cardiovascular disease, but little is known
      about its effect on CH or the mechanisms. We herein investigated the effect of
      STA on isoproterenol-induced CH and the underlying mechanisms. Treatment with STA
      significantly increased the ratios of heart weight/body weight, left ventricle
      weight/body weight and the cross-sectional areas of cardiomyocytes. In addition,
      STA significantly decreased the mRNA levels of atrial natriuretic peptide, B-type
      natriuretic peptide and beta-myosin heavy chain. Furthermore, isoproterenol
      induced fibrosis in rats receiving STA was significant attenuated, as evidenced
      by decreased ratio of fibrotic area/total area and decreased mRNA levels of
      collagens I and III. Given down-regulation of interleukin-6, tumor necrosis
      factor-alpha, interferon-gamma (IFN-gamma) and IFN-1beta, treatment with STA
      significantly reversed the expressions of pro-inflammatory induced by
      isoproterenol. Moreover, STA attenuated the oxidative stress level in serum of
      isoproterenol-induced CH rats, as shown by increased activity of superoxide
      dismutase and decreased malondialdehyde level. STA inhibited the expressions of
      phosphorylated IkappaBalpha, NF-kappaB p65, JAK2 and STAT3 in vivo. Thus, both NF
      kappaB and JAK/STAT signalings played essential roles in mediating the anti-CH
      effect of STA. Collectively, STA has a potent protective effect on isoproterenol
      induced CH, with therapeutic implication for CH.

PMID- 28499194
TI  - Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice
      via the NF-kappaB pathway.
AB  - Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series
      of studies have shown that it has been shown to exhibit several biological
      properties, including anti-inflammatory, anti-oxidant, cardio-protective,
      vasodilatory, liver-protective and anti-cancer activities. However, so far the
      possible therapeutic effect of QC on psoriasis has not been reported. The present
      study was undertaken to evaluate the potential beneficial effect of QC in
      psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model,
      and to further elucidate its underlying mechanisms of action. Effects of QC on
      PASI scores, back temperature, histopathological changes, oxidative/anti
      oxidative indexes, pro-inflammatory cytokines and NF-kappaB pathway in IMQ
      induced mice were investigated. Our results showed that QC could significantly
      reduce the PASI scores, decrease the temperature of the psoriasis-like lesions,
      and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC
      effectively attenuated levels of TNF-alpha, IL-6 and IL-17 in serum, increased
      activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin
      tissue induced by IMQ in mice. The mechanism may be associated with the down
      regulation of NF-kappaB, IKKalpha, NIK and RelB expression and up-regulation of
      TRAF3, which were critically involved in the non-canonical NF-kappaB pathway. In
      conclusion, our present study demonstrated that QC had appreciable anti-psoriasis
      effects in IMQ-induced mice, and the underlying mechanism may involve the
      improvement of antioxidant and anti-inflammatory status and inhibition on the
      activation of the NF-kappaB signaling. Hence, QC, a naturally occurring flavone
      with potent anti-psoriatic effects, has the potential for further development as
      a candidate for psoriasis treatment.

PMID- 28499195
TI  - Using the Rubik's Cube to directly produce paper analytical devices for
      quantitative point-of-care aptamer-based assays.
AB  - In this article, we describe a facile method named as Rubik's Cube stamping (RCS)
      for equipment-free fabrication of microfluidic paper-based analytical devices
      (MUPADs). RCS is inspired by the worldwide ubiquitous RC toy and requires no
      specialized electric equipment other than a classical six-faced RC that is
      assembled with home-made small iron components. It can pattern various rosin
      microstructures in paper simply by either using different functional faces of the
      modified RC or applying its internal pivot mechanism to adjust the components'
      patterning forms on one functional face. Such a versatile stamping method is
      quite simple and inexpensive, and thus holds potential for producing rosin
      patterned MUPADs by untrained users in resource-limited environments such as
      small laboratories and private clinics, or even at home and in the field.
      Moreover, a set of one-channel devices are fabricated to design a point-of-care
      aptamer-based assay with near sample-in-answer-out capability that integrates
      enzymatic reactions for robust yet efficient signal amplification and a personal
      glucometer for portable, user-friendly, rapid and quantitative readout. Its
      utility is well demonstrated with the sensitive and specific detection of
      adenosine as a model target in buffer samples and undiluted human urine within
      several minutes. With the advantages of low cost, simplicity, portability,
      rapidity, and aptamer variety, this general point-of-care assay system reported
      here may find broad applications including home healthcare, field-based
      environmental monitoring or food analysis and emergency situations.

PMID- 28499196
TI  - Binding-induced DNA walker for signal amplification in highly selective
      electrochemical detection of protein.
AB  - A binding-induced DNA walker-assisted signal amplification was developed for
      highly selective electrochemical detection of protein. Firstly, the track of DNA
      walker was constructed by self-assembly of the high density ferrocene (Fc)
      labeled anchor DNA and aptamer 1 on the gold electrode surface. Sequentially, a
      long swing-arm chain containing aptamer 2 and walking strand DNA was introduced
      onto gold electrode through aptamers-target specific recognition, and thus
      initiated walker strand sequences to hybridize with anchor DNA. Then, the DNA
      walker was activated by the stepwise cleavage of the hybridized anchor DNA by
      nicking endonuclease to release multiple Fc molecules for signal amplification.
      Taking thrombin as the model target, the Fc-generated electrochemical signal
      decreased linearly with logarithm value of thrombin concentration ranging from
      10pM to 100nM with a detection limit of 2.5pM under the optimal conditions. By
      integrating the specific recognition of aptamers to target with the enzymatic
      cleavage of nicking endonuclease, the aptasensor showed the high selectivity. The
      binding-induced DNA walker provides a promising strategy for signal amplification
      in electrochemical biosensor, and has the extensive applications in sensitive and
      selective detection of the various targets.

PMID- 28499197
TI  - Biomolecular stiffness detection based on positive frequency shift of CMOS
      compatible gigahertz solidly mounted resonators.
AB  - In this work, gigahertz solidly mounted resonators (SMRs) (2.5GHz) were designed
      and fabricated to construct a novel particle-resonator system to achieve the
      biomolecular stiffness sensing in real time. The positive frequency shift of the
      system was used to estimate the stiffness of biomolecules connecting between the
      SMR and attached particles. The working principle was revealed by the
      mathematical analysis of the general block-spring model of the system. Further
      interpretations about the mechanism of such elastic interaction from the
      perspective of acoustic resonant modes of SMRs were given by finite element
      method. Biotin-streptavidin, antibody and antigen binding system were used as
      model molecular linkers to study the frequency shift varied with different
      particle diameters and particle densities. Different linker stiffness was
      realized by adjusting the concentrations of antigens connected with particles
      which form specific binding with antibodies immobilized on the SMR. The results
      fairly agree with the simulation results demonstrating the proposed particle
      resonator system as an effective method to realize the real-time biomolecular
      stiffness detection.

PMID- 28499198
TI  - A Point-of-Need infrared mediated PCR platform with compatible lateral flow strip
      for HPV detection.
AB  - With the increasing need of monitoring the epidemiology of serious infectious
      diseases, food hygiene, food additives and pesticide residues, it is urgent to
      develop portable, easy-to-use, inexpensive and rapid molecular diagnostic tools.
      Herein, we demonstrate a prototype of IR mediated Conducting Oil and CarbOn
      Nanotube circUlaTing PCR (IR-COCONUT PCR) platform for nucleic acid
      amplification. The presented platform offers a new solution for miniaturized PCR
      instruments with non-contact heaters by using conducting oil and carbon nanotube
      as a medium in IR mediated PCR. This novel platform offers accurate and flexible
      control of temperature through the integration of PID (proportional-integral
      derivative) algorithms to manipulate the duty cycle of the voltage signals of IR
      LED and a peristaltic pump. The ramping rate of the introduced platform in
      current study is 1.5 degrees C/s for heating speed and -2.0 degrees C/s for
      cooling speed. This platform fulfills 30 thermal cycles within 50min which is a
      match to the conventional bench-top PCR thermo cyclers. For demonstration
      purpose, human papillomavirus (HPV) patient cervical swab specimens were
      examined. Downstream lateral flow strip (LFS) was also developed to quantity the
      PCR products from the IR-COCONUT PCR device within 25min. This PCR platform
      together with the compatible LFS shows great potential for in-field and Point-of
      Need (PoN) testing of genetic or contagious diseases.

PMID- 28499199
TI  - Perovskite-type calcium titanate nanoparticles as novel matrix for designing
      sensitive electrochemical biosensing.
AB  - In this work, novel perovskite-type calcium titanate nanoparticles (CaTiO3NPs)
      were for the first time exploited for the immobilization of proteins and the
      development of electrochemical biosensor. The CaTiO3NPs were synthesized with a
      simple and cost-effective route at low temperature, and characterized by scanning
      electron microscopy, X-ray photoelectron spectroscopic spectrum, electrochemical
      impedance spectrum, UV-visible spectroscopy, Fourier transform infrared spectrum,
      and cyclic voltammetry, respectively. The results indicated that CaTiO3NPs
      exhibited large surface area, and greatly promoted the direct electron transfer
      between enzyme molecules and electrode surface. The immobilized enzymes on this
      matrix retained its native bioactivity and exhibited a surface controlled, quasi
      reversible two-proton and two-electron transfer reaction with an electron
      transfer rate of 3.35s-1. Using glucose oxidase as model, the prepared glucose
      biosensor showed a high sensitivity of 14.10+/-0.5mAM-1 cm-2, a wide linear range
      of 7.0*10-6 to 1.49*10-3M, and a low detection limit of 2.3*10-6M at signal-to
      noise of 3. Moreover, the biosensor also possessed good reproducibility,
      excellent selectivity and acceptable storage life. This research provided a new
      type and promising perovskite nanomaterials for the development of efficient
      biosensors.

PMID- 28499200
TI  - Interactions of mussel-inspired polymeric nanoparticles with gastric mucin:
      Implications for gastro-retentive drug delivery.
AB  - Mussel-inspired polydopamine (pD) coatings have several unique characteristics
      such as durability, versatility, and robustness. In this study, we have designed
      pD-coated nanoparticles (NPs) of methoxy polyethylene glycol-b-poly(epsilon
      caprolactone) (mPEG-PCL@pD) as prospective nanoscale mucoadhesive platforms for
      gastro-retentive drug delivery. Successful pD coating on the NPs was confirmed by
      Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy.
      Mucoadhesion of pD-coated NPs was investigated in vitro using commercially
      available mucin under stomach lumen-mimetic conditions. Mucin-NP interactions
      were monitored by dynamic light scattering, which showed a significant change in
      particle size distribution of pD-coated NPs at mucin/NP ratios of 1:1, 1:2, and
      1:4w/w. Turbidity measurements indicated the formation of large mucin-NP
      aggregates causing a significant increase in turbidity at mucin/NP ratios of 2:1
      and 4:1w/w. pD-coated NPs exhibited a significantly higher mucin adsorption
      ability compared to uncoated NPs at mucin/NP ratios of 1:4, 1:2, and 1:1w/w. Zeta
      potential measurements demonstrated that mucin-pD-coated NP interactions were not
      electrostatic in nature. An ex vivo wash-off test conducted using excised sheep
      stomach revealed that 78% of pD-coated NPs remained attached to the mucosa after
      8h of incubation, compared to only 33% of uncoated NPs. In vitro release of
      rifampicin, used as a model drug, showed a similar controlled release profile
      from both pD-coated and uncoated NPs. Our results serve to expand the versatility
      of mussel-inspired coatings to the design of mucoadhesive nanoscale vehicles for
      oral drug delivery.

PMID- 28499201
TI  - Folate-functionalized assembly of low density lipoprotein/sodium carboxymethyl
      cellulose nanoparticles for targeted delivery.
AB  - In this study, well-defined folate (FA)-functionalized low density lipoproteins
      (LDL)/sodium carboxymethyl cellulose (CMC) nanoparticles (NP) were first
      formulated, utilized in tumor targeting and pH-triggered drug release. CMC was
      modified with FA before the preparation of NP. A model anti-tumor drug,
      doxorubicin (DOX), was effectively loaded into the LDL/CMC-FA NP by ionic bonding
      and hydrophobic interactions. To enhance non-covalent encapsulation stability,
      self-assembly of DOX-loaded LDL/CMC-FA NP (NP-DOX) was cross-linked by
      multivalent cations such as Ca2+ (Ca2+-NP-DOX). The active targeting efficiency
      of NP-DOX and Ca2+-NP-DOX was tested against KB cells (FA-receptor over
      expressing cells, FR+) and A549 cells (FA-receptor negative-expressing cells, FR
      ), using FA non-modified DOX-loaded LDL/CMC NP (NG-DOX) as control. The
      competition assay proved that free FA molecules prevented the cellular uptake of
      the NP by competitive binding to the FA receptors on the surface of KB cells.
      This new pH-responsive and FA-targeted nanocarrier may be a promising efficient
      drug delivery system for potential cancer therapy.

PMID- 28499202
TI  - Novel dual VES phospholipid self-assembled liposomes with an extremely high drug
      loading efficiency.
AB  - Vitamin E succinate (VES), a unique selective anti-cancer drug, has attracted
      much attention for its ability to induce apoptosis in various cancer cells.
      Importantly, it has been reported that VES is largely non-toxic to normal cells.
      However, poor aqueous solubility and bioavailability extensively restricted its
      clinical utility. In this report, dual VES phospholipid conjugate (di-VES-GPC)
      prodrug based liposomes were prepared in order to develop an efficient delivery
      system for VES. Di-VES-GPC was first synthesized by conjugating VES with l-alpha
      glycerophosphorylcholine (GPC) using N,N'-dicyclohexylcarbodiimide (DCC) as a
      coupling agent. The di-VES-GPC prodrug was able to self-assemble into liposomes
      by reverse-phase evaporation method. The structure of the liposomes was
      characterized by dynamic light scattering (DLS), transmission electron microscopy
      (TEM) and cryo-TEM. The results showed that di-VES-GPC assembled liposomes were
      spherical with an average diameter approximately 183nm. Cryo-TEM data confirmed
      the formation of multilamellar liposomes with the bilayer thickness about 5nm by
      the assembly of the conjugate without any excipient. The VES drug loading highly
      reaches up to 82.8wt% in the liposomes after a simple calculation. Furthermore,
      the in vitro release behavior of di-VES-GPC liposomes was evaluated in different
      media. It was found that the liposomes could release free VES at a weakly acidic
      microenvironment but exhibited good stability under a simulated biological
      condition. The cellular uptake and intracellular drug release tests demonstrated
      that di-VES-GPC liposomes could be internalized effectively and converted into
      parent drug VES in cancer cells. Furthermore, in vitro antitumor activities of
      the di-VES-GPC liposomes were evaluated by MTT assay and flow cytometry. It was
      revealed that the liposomes presented comparable cytotoxicities to free VES.
      Taken together, the di-VES-GPC liposomes might provide an excellent formulation
      of VES which have potential in the treatment of cancers.

PMID- 28499203
TI  - Efficient protein digestion using immobilized trypsin onto tannin modified Fe3O4
      magnetic nanoparticles.
AB  - Fe3O4 magnetic nanoparticles (MNPs) were prepared via solvothermal method. A
      commercially available trypsin was covalently immobilized onto MNPs modified with
      tannin (T) via a novel binding process. The morphology, structure, surface and
      magnetic properties of the obtained nanostructures were characterized
      comprehensively. The Fe3O4 MNPs had a saturation magnetization value of
      60.18emu/g at room temperature, while the tannin modified Fe3O4 MNPs, and the
      trypsin immobilized on tannin modified-Fe3O4 MNPs possessed a saturation
      magnetization value of 57.82emu/g and 55.16emu/g, respectively, which indicated
      the decent tannin coating and trypsin immobilization. The general applicability
      of the immobilized trypsin for proteomic studies was confirmed by enzymatic
      digestion of widely used bovine serum albumin (BSA). The immobilized trypsin was
      investigated by conducting the tryptic digestion of BSA within 1min, 5min and
      15min. Also, microwave-assisted digestion was carried out for 15s. The digested
      protein fragments were identified by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry (MALDI-TOF MS), and a satisfactory peptide
      numbers of 39, and a superior sequence coverage of 84% for 1min digestion were
      obtained. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE) analysis confirmed the satisfactory digestion of BSA and egg white proteins
      by immobilized trypsin.

PMID- 28499204
TI  - Simultaneous determination of nine phytohormones in seaweed and algae extracts by
      HPLC-PDA.
AB  - An RP-HPLC-PDA method for the simultaneous analysis of 9 compounds deriving from
      the phytohormones class was developed and optimized, namely indoleacetic acid
      (IAA), indolebutyric acid (IBA), phenyleacetic acid (PAA), naphtyleacetic acid
      (NAA), trans-zeatin (TZ), kinetin (KA), isopentenyladenine (IA), 6
      benzylaminopurine (6-BA) and abscisic acid (ABA). Validation of the method was
      performed on the SFE-CO2 extract made out of the mixture of Baltic algae. The
      regression coefficients for plant hormones were in the range from 0.997 to 0.999.
      The LOD and LOQ were on the levels from 0.05-0.29 and 0.15-0.88mg/L,
      respectively. Developed method was used for the separation and determination
      plant hormones in extracts obtained by SFE-CO2 (supercritical fluid extraction)
      made out of the mixture of Baltic algae, Cladophora glomerata and Spirulina sp.
      In the extract of Baltic seaweed 2 of tested compounds were present in the
      concentration of 154,45+/-20,63MUg/g for TZ and 362,47+/-13,00MUg/g for PAA,
      whereas in Cladophora glomerata extract contained PAA and IAA in the
      concentration of 229,30+/-7,90MUg/g and 23,91+/-0,80MUg/g, respectively (all
      values per g of extract). The differences in the hormones levels may occur due to
      the different scale of extract preparation (laboratory or industrial) and other
      factors like the place of algae collection, year of collection or the way of
      biomass preparation.

PMID- 28499205
TI  - Comparative metabolomics analysis for the compatibility and incompatibility of
      kansui and licorice with different ratios by UHPLC-QTOF/MS and multivariate data
      analysis.
AB  - Kansui, the root of Euphorbia kansui T.N. Liou ex T.P. Wang (Euphorbiaceae), is a
      well-known poisonous traditional Chinese medicine (TCM). However, many monographs
      of TCM indicated that it cannot be co-used with licorice, as kansui-licorice is a
      typical "eighteen incompatible" medicaments. Our previous studies have indicated
      that kansui was effective in treating malignant pleural effusion (MPE), and the
      efficacy could be weakened by the co-use of licorice, even causing serious
      toxicity at the given ratio. Nevertheless, the actual mechanisms of their dosage
      toxicity-efficacy relationship need to be well clarified. The present study aimed
      to investigate the effect of individual and combined use of kansui and licorice
      on MPE rats, and explain the underlying mechanisms from a metabolomic
      perspective. Urine samples were analyzed by ultra-high-performance liquid
      chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC
      QTOF/MS). Partial least-squares discriminate analysis (PLS-DA) models were built
      to evaluate the interaction between kansui and licorice. Seven potential
      biomarkers contribute to the separation of model group and control group were
      tentatively identified. And selenoamino acid metabolism and nicotinate and
      nicotinamide metabolism with the impact-value 0.31 and 0.24, respectively, were
      filtered out as the most important metabolic pathways. Kansui and kansui-licorice
      at a ratio of 4:1 can treat MPE rats by adjusting abnormal metabolic pathways to
      the normal state, while it may have opposite result with kansui-licorice 1:4. The
      different influences to the two metabolic pathways may partially explain the
      dosage-toxicity-efficacy relationship of kansui-licorice with different ratios.
      The results could offer valuable insights into the compatibility property changes
      for the two herbs.

PMID- 28499206
TI  - Simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis
      in rabbit aqueous humor by LC-MS/MS: Application to ocular pharmacokinetic
      studies.
AB  - This study aims to establish a fast and sensitive LC-MS/MS method for
      simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis
      in rabbit aqueous humor. Aqueous humor samples were processed by protein
      precipitation and then separated on a Thermo Syncronis C18 column (50mm*2.1mm,
      5MUm) with a mobile phase using acetonitrile-0.05% formic acid (28:72, v/v).
      Detection of the analytes and the internal standard (coptisine) were performed in
      positive electrospray ionization with selected reaction monitoring. The method
      showed good linearity (r>0.9931) for all the seven alkaloids. This fully
      validated method was applied to the studies of aqueous humor pharmacokinetics of
      seven alkaloids from Rhizoma Corydalis Decumbentis and the effects of borneol on
      corneal penetration of these alkaloids into aqueous humor. This is the first work
      that presents a reliable LC-MS/MS method for simultaneous determination of seven
      alkaloids in rabbit aqueous humor and its application of ocular pharmacokinetics
      of seven alkaloids from Rhizoma Corydalis Decumbentis.

PMID- 28499207
TI  - Thin high-order shims for small dipole NMR magnets.
AB  - An NMR shim coil design method that addresses the severe spatial constraints of
      miniaturized dipole magnets is introduced. The fundamental design element, a
      collection of straight wires, is shown to be sufficient for producing a complete
      set of shim fields of high mathematical order. In accord with these theoretical
      considerations, a shim set is constructed using four wires in each of four
      directions to create all first through fourth order fields, except one. This shim
      set, with its supporting structure, occupies only 2mm of the available 5mm gap in
      a small 1.6T magnet. However, the fields produced by the individual wires are
      found to differ significantly from theoretical expectations. To produce the
      desired harmonic shim fields, the magnetic field of each of the 32 wires is
      mapped in three dimensions, and linear combinations of these maps are formed. The
      resulting shim fields are found to be very pure. The shims are used in a
      prototype high-resolution NMR magnet in which the 1.0mm sample size is only
      possible due to the thinness of the shim set. The resulting spectra demonstrate
      shimming to high resolution (<25ppb FWHM) without undue heating effects.

PMID- 28499208
TI  - Whole-brain resting-state functional connectivity identified major depressive
      disorder: A multivariate pattern analysis in two independent samples.
AB  - BACKGROUND: there has been a recent increase in the use of connectome-based
      multivariate pattern analysis (MVPA) of resting-state functional magnetic
      resonance imaging (fMRI) data aimed at distinguishing patients with major
      depressive disorder (MDD) from healthy controls (HCs). However, the validity of
      this method needs to be confirmed in independent samples. METHOD: we used resting
      state fMRI to explore whole-brain functional connectivity (FC) patterns
      characteristic of MDD and to confirm the effectiveness of MVPA in distinguishing
      MDD versus HC groups in two independent samples. The first sample set included 29
      MDD patients and 33 HCs and second sample set included 46 MDD patients and 57
      HCs. RESULTS: for the first sample, we obtained a correct classification rate of
      91.9% with a sensitivity of 89.6% and specificity of 93.9%. For the second
      sample, we observed a correct classification rate of 86.4% with a sensitivity of
      84.8% and specificity of 87.7%. With both samples, we found that the majority of
      consensus FCs used for MDD identification were located in the salience network,
      default mode network, the cerebellum, visual cortical areas, and the affective
      network. LIMITATION: we did not analyze potential structural differences between
      the groups. CONCLUSION: results suggest that whole-brain FC patterns can be used
      to differentiate depressed patients from HCs and provide evidence for the
      potential use of connectome-based MVPA as a complementary tool in the clinical
      diagnosis of MDD.

PMID- 28499209
TI  - Precursors in adolescence of adult-onset bipolar disorder.
AB  - BACKGROUND: Although the estimated contribution of genetic factors is high in
      bipolar disorder, environmental factors may also play a role. This Swedish
      register-based cohort study of men examined if physical and psychological
      characteristics in late adolescence, including factors previously linked with
      bipolar disorder (body mass index, asthma and allergy), are associated with
      subsequent bipolar disorder in adulthood. Unipolar depression and anxiety are
      analysed as additional outcomes to identify bipolar disorder-specific
      associations. METHODS: A total of 213,693 men born between 1952 and 1956, who
      participated in compulsory military conscription assessments in late adolescence
      were followed up to 2009, excluding men with any psychiatric diagnoses at
      baseline. Cox regression estimated risk of bipolar disorder, depression and
      anxiety in adulthood associated with body mass index, asthma, allergy, muscular
      strength stress resilience and cognitive function in adolescence. RESULTS: BMI,
      asthma and allergy were not associated with bipolar disorder. Higher grip
      strength, cognitive function and stress resilience were associated with a reduced
      risk of bipolar disorder and the other disease outcomes. LIMITATIONS: The sample
      consisted only of men; even though the characteristics in adolescence pre-dated
      disease onset, they may have been the consequence of prodromal disease.
      CONCLUSIONS: Associations with body mass index and asthma found by previous
      studies may be consequences of bipolar disorder or its treatment rather than risk
      factors. Inverse associations with all the outcome diagnoses for stress
      resilience, muscular strength and cognitive function may reflect general risks
      for these psychiatric disorders or intermediary factors.

PMID- 28499210
TI  - Micro-scale environment and mental health in later life: Results from the
      Cognitive Function and Ageing Study II (CFAS II).
AB  - BACKGROUND: Poor micro-scale environmental features, such as graffiti and broken
      windows, have been associated with crime and signs of social disorder with a
      potential impact on mental health. The aim of this study is to investigate the
      association between micro-scale environment and mental health problems in later
      life, including cognitive (cognitive impairment and dementia) and common mental
      disorders (depressive and anxiety symptoms). METHODS: The method of visual image
      audits was used to collect micro-scale environmental data for 3590 participants
      in the Cognitive Function and Ageing Study II, a population-based multicentre
      cohort of people aged 65 or above in England. Multilevel logistic regression was
      used to examine the associations between the quality of micro-scale environment
      and mental health problems taking into account urban/rural difference. RESULTS:
      Poor quality of micro-scale environment was associated with nearly 20% increased
      odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17;
      95% CI: 0.99, 1.38) while the direction of association for cognitive disorders
      differed across urban and rural settings. Although higher odds of cognitive
      disorders were found in rural settings, living in a poor quality environment was
      associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95%
      CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR:
      0.80; 95% CI: 0.57, 1.11). LIMITATIONS: The causal direction could not be fully
      determined due to the cross-sectional nature of the data. The visual nature of
      the environmental assessment tool means it likely does not fully capture features
      related to the availability of local support services, or opportunities for
      social participation and interaction. CONCLUSIONS: The quality of micro-scale
      environment appears to be important to mental health in older people.
      Interventions may incorporate the environmental aspect to reduce cognitive and
      common mental disorders.

PMID- 28499211
TI  - Oxytocin receptor and G-protein polymorphisms in patients with depression and
      separation anxiety.
AB  - BACKGROUND: The impact of combined variants of Oxytocin Receptor (OXTR) and G
      protein beta3 subunit genes was investigated in relation to retrospective reports
      of childhood as well as contemporary adult separation anxiety (SA), based on
      evidence of a beta/gamma dimer-mediated signaling for OXTR. METHODS: A case
      control association study (225 healthy adults and 188 outpatients with
      depression) was performed to establish Risk-Combined Genotype (RCG) of the
      studied variants (OXTR rs53576 and the functional Gbeta3 subunit rs5443). Current
      SA was evaluated by the ASA-27 and retrospective childhood symptoms by the SASI.
      GG genotype of OXTR rs53576 combined with T-carrier genotype of Gbeta3 rs5443
      represented the RCG. RESULTS: Compared to non-RCG, those with RCG had
      significantly higher levels of childhood and adult SA. The RCG was significantly
      associated with childhood SA threshold score (OR=2.85, 90%CI: 1.08-7.50).
      Childhood SA was, in turn, strongly associated with a threshold SA score in
      adulthood (OR=15.58; 95% CI: 4.62-52.59). LIMITATIONS: Although the overall
      sample size is sizable, comparisons among subgroups with specific combination of
      alleles are based on relatively small numbers. CONCLUSIONS: Our study indicates
      that variations in OXTR and Gbeta3 genes are specifically associated with
      presence and severity of SA in childhood and adulthood, but not with depression
      or anxiety in general. Because there is increasing interest in oxytocin in social
      behavior, the gene-SA associations identified have potential translational and
      clinical relevance.

PMID- 28499212
TI  - Quantification of Pasteurella multocida in experimentally infected pigs using a
      real-time PCR assay.
AB  - The aim of the study was to quantify Pasteurella multocida in experimentally
      infected pigs using a new qPCR assay based on the sodA gene and validated with 35
      P. multocida strains, including strains isolated from pigs with pneumonia,
      clinically healthy pigs (nasal cavities), and human infections. The specificity
      of the test was verified with a collection of 60 strains of bacterial species
      other than P. multocida. The estimated detection threshold was 10 genome
      equivalents per microliter. The amplification efficiency and value of the
      correlation coefficients were 95.5% (+/-3.5%) and 0.995 (+/-0.005), respectively.
      Analysis of P. multocida suspensions in Buffered Peptone Water Broth and of
      samples prepared from lungs experimentally spiked with P. multocida revealed
      detection thresholds of 1.4CFU/MUl and 8.4CFU/MUl, respectively. In live pigs,
      experimentally-infected, approximately 105, 107 and 108genomeequivalents/ml of P.
      multocida DNA was detected on Day 8 post-infection in the nasal cavities, tonsils
      and trachea samples, respectively. In dead pigs, approximatively
      107genomeequivalents/ml of P. multocida DNA was detected in the lung tissue with
      pneumonia. The qPCR assay's diagnostic specificity and sensitivity were 100% and
      96%, respectively. This new qPCR assay should be a very useful tool for
      controlling enzootic pneumonia and studying the dynamics of infections in pig
      herds.

PMID- 28499213
TI  - Effect of Excoecaria agallocha on non-specific immune responses and disease
      resistance of Oreochromis niloticus against Streptococcus agalactiae.
AB  - The current study was designed to evaluate the effects of Excoecaria agallocha
      leaf extracts on immune mechanisms and resistance of tilapia, Oreochromis
      niloticus, after challenge with Streptococcus agalactiae. Fish were divided into
      6 groups; groups 1-5 fed with E. agallocha leaf extracts at 10, 20, 30, 40 and
      50mgkg-1 level, respectively. Group 6 were fed without extract addition and acted
      as control. E. agallocha extracts were administered as feed supplement in fish
      diet for 28days and the hematological, immunological, and growth performance
      studies were conducted. Fish were infected with S. agalactiae at a dose of
      15*105CFUmL-1 and the total white blood cell (WBC), phagocytosis and respiratory
      burst activities of leukocytes, serum bactericidal activity, lysozyme, total
      protein, albumin, and globulin levels were monitored and mortalities recorded for
      15days post infection. Results revealed that feeding O. niloticus with 50mgkg-1
      of E. agallocha enhanced WBC, phagocytic, respiratory burst, serum bactericidal
      and lysozyme activities on day 28 pre-challenge and on 3rd, 6th, 9th, 12th and
      15th day post-challenge as compared to control. Total protein and albumin were
      not enhanced by E. agallocha diet. E. agallocha increased the survival of fish
      after challenge with S. agalactiae. The highest mortality rate (97%) was observed
      in control fish and the lowest mortality (27%) was observed with group fed with
      50mgkg-1 extract. The results indicate that dietary intake of E. agallocha
      methanolic leaf extract in O. niloticus enhances the non-specific immunity and
      disease resistance against S. agalactiae pathogen.

PMID- 28499214
TI  - Speciation of potential anti-diabetic vanadium complexes in real serum samples.
AB  - In this work the speciation in real serum samples of five VIVO complexes with
      potential application in the therapy of diabetes was studied through EPR
      spectroscopy as a function of V concentration (45.4, 90.9 and 454.5MUM) and time
      (0-180min). [VO(dhp)2], [VO(ma)2], [VO(acac)2], [VO(pic)2(H2O)], and
      [VO(mepic)2], where Hdhp indicates 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, Hma
      maltol, Hacac acetylacetone, Hpic picolinic acid, and Hmepic 6-methylpicolinic
      acid, were examined. The distribution of VIVO2+ among the serum bioligands was
      calculated from the thermodynamic stability constants in the literature and
      compared with the experimental results. EPR results, which confirm the
      prediction, depend on the strength of the ligand L and geometry assumed by the
      bis-chelated species at physiological pH, cis-octahedral or square pyramidal.
      With dhp, the strongest chelator, the system is dominated by [VO(dhp)2] and/or
      cis-VO(dhp)2(Protein); with intermediate strength chelators, i.e. maltolate,
      acetylacetonate and picolinate, by cis-VO(ma)2(Protein), [VO(acac)2] or
      [VO(pic)(citrH-1)]3-/[VO(pic)(lactH-1)]- (citr=citrate and lact=lactate) when the
      V concentration overcomes 100-200MUM and by (VO)(hTf)/(VO)2(hTf) when
      concentration is lower than 100MUM; with the weakest chelator, 6
      methylpicolinate, (VO)(hTf)/(VO)2(hTf), (VO)(HSA) (hTf = human serum transferrin
      and HSA = human serum albumin), and VO(mepic)(Protein)(OH) are the major species
      at concentration higher than 100-200MUM, whereas hydrolytic processes are
      observed for lower concentrations. For [VO(dhp)2], [VO(ma)2], [VO(acac)2] and
      [VO(pic)2(H2O)], the EPR spectra remain unaltered with elapsing time, while for
      mepic they change significantly because the hydrolyzed VIVO species are complexed
      by the serum bioligands, in particular by lactate. The rate of oxidation in the
      serum is [VO(dhp)2]>[VO(ma)2]>[VO(acac)2] and reflects the order of E1/2 values.

PMID- 28499215
TI  - Numerical study on the air conditioning characteristics of the human nasal
      cavity.
AB  - The air-conditioning characteristics of the human nasal cavity were investigated
      using computational fluid dynamics. The wall layer was modeled as a heat
      conducting layer consisting of water with constant thickness placed on top of
      epithelial cells. By assuming constant tissue temperature, prescribed to be 36 
      degrees C, which is close to the alveolar condition, the proposed wall model
      yielded a spatially varying surface temperature distribution that is in
      reasonable agreement with the measurement studies in the literature. The results
      show that the regions of the main airway between the nasal valve, and the
      anterior of the middle turbinate were shown to have relatively low temperatures,
      whereas the superior meatus exhibited relatively high temperature. Water vapor
      flux evaluated at the surface of the mucus layer was found to be quite large in
      the region between the posterior of the vestibule and the anterior of the middle
      turbinate. Comparing the results obtained from the present model to those
      obtained with a constant surface temperature boundary condition of 32.6  degrees
      C or 34  degrees C revealed that temperature, and absolute humidity of the
      airflow increased faster through the turbinated airway passage. Even in the
      presence of sizable differences in the distributions of surface temperature and
      water vapor concentration, distributions of relative humidity of the air were
      found to be quite similar regardless of temperature boundary conditions.

PMID- 28499216
TI  - Biobrick chain recommendations for genetic circuit design.
AB  - Synthetic biology databases have collected numerous biobricks to accelerate
      genetic circuit design. However, selecting biobricks is a tough task. Here, we
      leverage the fact that these manually designed circuits can provide underlying
      knowledge to support biobrick selection. We propose to design a recommendation
      system based on the analysis of available genetic circuits, which can narrow down
      the biobrick selection range and provide candidate biobricks for users to choose.
      A recommendation strategy based on a Markov model is established to tackle this
      issue. Furthermore, a biobrick chain recommendation algorithm Sira is proposed
      that applies a dynamic programming process on a layered state transition graph to
      obtain the top k recommendation results. In addition, a weighted filtering
      strategy, WFSira, is proposed to augment the performance of Sira. The
      experimental results on the Registry of Standard Biological Parts show that Sira
      outperforms other algorithms significantly for biobrick recommendations, with
      approximately 30% improvement in terms of recall rate. It is also able to make
      biobrick chain recommendations. WFSira can further improve the recall rate of
      Sira by an average of 7.5% for the top 5 recommendations.

PMID- 28499217
TI  - Adhesive coatings based on melanin-like nanoparticles for surgical membranes.
AB  - Adhesive coatings for implantable biomaterials can be designed to prevent
      material displacement from the site of implant. In this paper, a strategy based
      on the use of melanin-like nanoparticles (MNPs) for the development of adhesive
      coatings for polysaccharidic membranes was devised. MNPs were synthesized in
      vitro and characterized in terms of dimensions and surface potential, as a
      function of pH and ionic strength. The in vitro biocompatibility of MNPs was
      investigated on fibroblast cells, while the antimicrobial properties of MNPs in
      suspension were evaluated on E. coli and S. aureus cultures. The manufacturing of
      the adhesive coatings was carried out by spreading MNPs over the surface of
      polysaccharidic membranes; the adhesive properties of the nano-engineered coating
      to the target tissue (intestinal serosa) were studied in simulated physiological
      conditions. Overall, this study opens for novel approaches in the design of
      naturally inspired nanostructured adhesive systems.

PMID- 28499218
TI  - Dissolution and physicochemical stability enhancement of artemisinin and
      mefloquine co-formulation via nano-confinement with mesoporous SBA-15.
AB  - The objective of this study is to enhance the dissolution rate, supersaturation
      and physicochemical stability of combination of two poorly water-soluble anti
      malarial drugs, artemisinin (ART) and mefloquine (MFQ), by encapsulating them
      inside mesoporous silica (SBA-15) via co-spray drying. Characteristic studies
      such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM)
      and scanning electron microscope (SEM) clearly indicate the amorphization of the
      crystalline drugs. ART/MQF/SBA-15 formulations show a superior dissolution
      enhancement with a burst release of more than 95% of drugs within 30min. In
      addition, the combination formulation exhibits a stable supersaturation
      enhancement by 2-fold higher than that of the untreated crystalline counterparts.
      ART/MQF/SBA-15 samples possess excellent physicochemical stability under 2
      different moderate storage conditions for 6 months. The amorphization of ART and
      MFQ via nano-confinement using mesoporous SBA-15 is a potentially promising
      approach to enhance the solubility of poorly water-soluble anti-malarial drugs
      that co-formulated into a single dosage form.

PMID- 28499219
TI  - Oxidant and anti-oxidant status in common brain tumors: Correlation to TP53 and
      human biliverdin reductase.
AB  - OBJECTIVE: To assess oxidant and antioxidant status in patients with common brain
      tumors; namely meningiomas, low-grade gliomas (LGG) and high-grade gliomas (HGG)
      and to compare with normal brain tissues. PATIENTS AND METHODS: Almost nine
      biomarkers were measured in 59 brain tumors obtained during surgery and 15 normal
      brain tissues that were collected during autopsy. Results were compared between
      two groups. RESULTS: In general, protein oxidation and lipid peroxidation
      increased while antioxidant capacity decreased significantly in tumors compared
      to the controls (p<0.05) and higher the grade of the tumor, higher the levels of
      oxidation and lower the anti-oxidation. CONCLUSIONS: Reactive oxygen species may
      play a crucial role in the pathogenesis of these common brain tumors. As the
      processes at the molecular level understood, targeted-treatment adjunct to
      surgical removal will be possible to cope with these devastating brain tumors.

PMID- 28499220
TI  - Effects of preadmission beta-blockers on neurogenic stunned myocardium after
      aneurysmal subarachnoid hemorrhage: A meta- analysis.
AB  - OBJECTIVE: Spontaneous subarachnoid hemorrhage is mostly caused by the rupture of
      an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent
      complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible
      pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads
      to subendocardial ischemia or coronary artery spasm. We designed this meta
      analysis to find out whether beta-blockers (BB) can significantly reduce the
      incidence of NSM and improve the outcomes of aSAH. PATIENTS AND METHODS: We
      systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline
      from inception to Feb 2016. All studies related to the preadmission beta-blocker
      with aSAH were included. RESULTS: Three retrospective studies and 691 patients
      were included. The incidence of mortality [OR=0.68, 95%CI (0.08-3.50), P=0.57],
      cardiac dysfunction [OR = 0.55, 95% CI (0.05-6.49), P=0.63], cerebral vasospasm
      (OR=0.52 95% CI(0.18-2.56), P=0.50] had no statistical difference between the
      preadmission BB group and no BB group. CONCLUSION: The preadmission beta-blocker
      cannot decrease the incidence of mortality, cardiac dysfunction, cerebral
      vasospasm in patients with aSAH. A further research of the usefulness of
      preadmission beta-blocker in patients with aSAH will be needed.

PMID- 28499221
TI  - A water quality management strategy for regionally protected water through health
      risk assessment and spatial distribution of heavy metal pollution in 3 marine
      reserves.
AB  - Severe water pollution and resource scarcity is a major problem in China, where
      it is necessary to establish water quality-oriented monitoring and intelligent
      watershed management. In this study, an effective watershed management method is
      explored, in which water quality is first assessed using the heavy metal
      pollution index and the human health risk index, and then by classifying the
      pollution and management grade based on cluster analysis and GIS visualization.
      Three marine reserves in Tianjin were selected and analyzed, namely the Tianjin
      Ancient Coastal Wetland National Nature Reserve (Qilihai Natural Reserve), the
      Tianjin DaShentang Oyster Reef National Marine Special Reserve (DaShentang
      Reserve), and the Tianjin Coastal Wetland National Marine Special Reserve (BinHai
      Wetland Reserve) which is under construction. The water quality and potential
      human health risks of 5 heavy metals (Pb, As, Cd, Hg, Cr) in the three reserves
      were assessed using the Nemerow index and USEPA methods. Moreover, ArcGIS10.2
      software was used to visualize the heavy metal index and display their spatial
      distribution. Cluster analysis enabled classification of the heavy metals into 4
      categories, which allowed for identification of the heavy metals whose pollution
      index and health risks were highest, and, thus, whose control in the reserve is a
      priority. Results indicate that heavy metal pollution exists in the Qilihai
      Natural Reserve and in the north and east of the DaShentang Reserve; furthermore,
      human health risks exist in the Qilihai Natural Reserve and in the BinHai Wetland
      Reserve. In each reserve, the main factor influencing the pollution and health
      risk were high concentrations of As and Pb that exceed the corresponding
      standards. Measures must be adopted to control and remediate the pollutants.
      Furthermore, to protect the marine reserves, management policies must be
      implemented to improve water quality, which is an urgent task for both local and
      national governments.

PMID- 28499222
TI  - The actual role of oxygen deficit in the linkage of the water quality and benthic
      phosphorus release: Potential implications for lake restoration.
AB  - Human activities in watersheds have resulted in huge accumulations of phosphorus
      (P) in sediments that have subsequently hindered restoration efforts of lake
      water quality managers worldwide. Much controversy exists about the factors that
      control the release of P from sediments (internal P loading). One of the main
      debates concerns the role of oxygen deficit (anoxia) in the regulation of water
      quality. Our results based on a comprehensive set of lakes worldwide demonstrate
      that internal P loading (IPtot) plays a significant role in water quality
      regulation. Internal P loading due to anoxia (IPanox) contributes significantly
      to the IPtot. However, this contribution is insufficient to significantly
      increase the chlorophyll a (Chl a) concentration in stratifying lakes. In the
      lakes of the north temperate and boreal zone, this is because the IPanox reaches
      surface water layer in the end of the growing season. Observed water quality
      implications of IPtot are most likely caused by the sedimentary P that actually
      originates from the shallow areas. These findings suggest limitations for the use
      of aeration (improvement of the oxygen conditions in the hypolimnion) in lake
      water quality restoration. Moreover, lake ecosystem managers can benefit from our
      model that enables to predict anoxia triggered sedimentary P release from the
      combination of lake characteristics. The final decision on the use of aeration is
      indeed unique to each lake, and lake specific targets should be considered.

PMID- 28499223
TI  - Decomposing the land-use specific response of plant functional traits along
      environmental gradients.
AB  - Environmental conditions affect functional trait variability within communities
      and thus shape ecosystem properties. With the ability of plants to adapt
      morphologically and physiologically to changing abiotic conditions, gradient
      analysis was shown to be a suitable tool to identify the drivers which determine
      trait values. Apart from direct environmental drivers and indirect gradients such
      as elevation, also anthropogenic effects (e.g. irrigation, grazing) can influence
      trait variability. Our aim was to assess the interactive effects of different
      environmental drivers on major plant traits and to investigate how these are
      modulated within two different land-use types (hay meadow vs. pasture). An
      elevational gradient spanning 1000m was decomposed into its underlying direct
      components (temperature, water input, length of growing season) for the
      investigation of gradual responses of five prominent functional traits
      (aboveground dry weight (AGDW), vegetative height (VegHt), specific leaf area
      (SLA), leaf dry matter content (LDMC), leaf nitrogen concentration (LNC)) for key
      species from two functional groups (grasses, forbs) in the two land
      use/management regimes. The present study revealed that the detailed analysis of
      single direct gradients provides substantial additional information on trait
      response which remains hidden or is even reversed if only indirect gradients such
      as elevation are analysed. However, trait response to the combination of the
      three direct gradients aligned surprisingly well with trait response to the
      indirect gradient underpinning the adequate representation of temperature, water
      input and length of growing season by elevation. The response of traits
      significantly depended on the management regime and corresponding intensity which
      was shown to play an overriding role and constrained and attenuated response
      ranges of traits to climatic gradients.

PMID- 28499224
TI  - Interspecies comparison of selected pollution biomarkers in dreissenid spp.
      inhabiting pristine and moderately polluted sites.
AB  - Stress biomarkers, which can outline impacts of contaminants in aquatic biota at
      the biochemical level, are increasingly used as early warning tools in
      environmental monitoring. Reliable biomarker based assessment schemes, however,
      request appropriate knowledge of baseline levels of selected endpoints, and the
      potential influence of a range of natural influencing factors (both abiotic and
      biotic) as well. In this study, we examined the interspecies variability of
      various biomarkers (metallothioneins (MT), ethoxyresorufin-O-deethylase activity
      (EROD), lipid peroxidation (LPO), DNA strand breaks (DNA_sb), vitellogenin-like
      proteins (Vtg)) in Dreissena polymorpha and Dreissena bugensis inhabiting either
      pristine- or moderately impacted sites of Lake Balaton (Hungary). Levels of all
      biomarkers considered revealed low interspecies variability in the two dreissenid
      species at all sampling sites, with consistently higher (but statistically
      insignificant) values in Dreissena polymorpha. Levels of all biomarkers varied
      within the two investigated seasons, with significant influence of the
      reproduction cycle particularly on the levels of metallothioneins and
      vitellogenin-like proteins. Each biomarker considered was elevated by October,
      with significantly higher values in the mussels inhabiting harbours.
      Insignificant spatial and temporal variability in the general health indicators
      (condition index, total protein content) of dreissenids was observed, which, in
      parallel with evident rise in biomarker levels, apparently suggest that the
      anthropogenic impacts in harbours affect mussel fitness yet at sub organismal
      level. Our data might serve useful basis for future environmental monitoring
      surveys, especially in habitats where the progressive replacement of Dreissena
      polymorpha by Dreissena bugensis is taking place, as the interspecies variability
      in susceptibility to chemical stress of the two species is well comparable.

PMID- 28499225
TI  - Environmental risk assessment of polycyclic musks HHCB and AHTN in consumer
      product chemicals in China.
AB  - An environmental risk assessment (ERA) framework was recently developed for
      consumer product chemicals in China using a tiered approach, applying an existing
      Chinese regulatory qualitative method in Tier Zero and, then, utilizing
      deterministic and probabilistic methods for Tiers One and Two. The exposure
      assessment methodology in the framework applied conditions specific to China
      including physical setting, infrastructure, and consumers' habits and practices.
      Furthermore, two scenarios were identified for quantitatively assessing
      environmental exposure: (1) Urban with wastewater treatment, and; (2) Rural
      without wastewater treatment (i.e., direct-discharge of wastewater). Upon a brief
      discussion on the framework methodology, this paper primarily presented a case
      study conducted using this new approach for assessing two fragrance chemicals,
      the polycyclic musks HHCB (Galaxolide, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta-[gamma]-2-benzopyran) and AHTN (Tonalide, 7-acetyl
      1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene). Both HHCB and AHTN are
      widely used as fragrances in a variety of consumer products in China, and
      occurrences of both compounds have been reported in wastewater influents,
      effluents, and sludge, in addition to surface water and sediments across several
      major metropolitan regions throughout China. This case study illustrated the very
      conservative nature of Tier Zero, which indicated a high risk potential of the
      fragrances to receiving water aquatic communities due to the fragrance's non
      ready biodegradability and eco-toxicity profiles. However, the higher-tiered
      assessments (including deterministic and site-specific probabilistic)
      demonstrated greater environmental realism with the conclusion of HHCB and AHTN
      posing minimal risk, consistent with local monitoring data as well as a recent
      similar study conducted in the United States.

PMID- 28499226
TI  - Effectiveness of a full-scale horizontal slow sand filter for controlling
      phytopathogens in recirculating hydroponics: From microbial isolation to full
      microbiome assessment.
AB  - The microbial disinfestation efficiency of an innovative horizontal-flow slow
      sand filter (HSSF) for treating nutrient solution spent from an experimental
      closed-loop nursery was evaluated by means of a combination of culture-dependent
      and independent molecular techniques. A dense inoculum of the fungal plant
      pathogen Fusarium oxysporum f.sp. lycopersici was applied in the fertigation
      system (106 cells per mL). Indigenous and introduced populations of eubacteria
      and fungi were assessed in the nutrient solution, the HSSF influent/effluent, and
      a sand bed transect by isolation on selective media, as well as by quantitative
      qPCR and next-generation sequencing (NGS) on target ribosomal genes. The HSSF
      effectively reduced viable Fusarium propagules and fungal gene content with an
      efficiency consistently above 99.9% (5 orders of magnitude down). On the other
      hand, Fusarium cells accumulated in the sand bed, indicating that physical
      entrapment was the main removal mechanism. The viability of retained Fusarium
      cells tended to decrease in time, so that treatment efficiency might be enhanced
      by antagonistic species from the genera Bacillus, Pseudomonas, and Trichoderma,
      also identified in the sand bed. Indigenous bacterial populations from the HSSF
      effluent were reduced by 87.2% and 99.9% in terms of colony forming units and
      gene counts, respectively, when compared to the influent. Furthermore, microbial
      populations from the HSSF effluent were different from those observed in the sand
      bed and the influent. In summary, the HSSF microbial disinfestation efficiency is
      comparable to that reported for other more intensive and costly methodologies,
      while allowing a significant recovery of water and nutrients.

PMID- 28499227
TI  - Organic carbon pools and soil biological fertility are affected by land use
      intensity in Mediterranean ecosystems of Sardinia, Italy.
AB  - Soil quality is mainly studied from the chemical and physical point of view,
      whereas soil biochemical and microbiological parameters are relatively more
      scarcely explored to assess the effect of management practices. This study aimed
      to evaluate soil organic carbon (SOC) and its pools; soil microbial activity
      parameters; and the Biological Fertility Index (BFI), in six land uses
      characteristics of the Mediterranean basin in north-eastern Sardinia. These land
      uses differed in management intensity and consisted of: tilled vineyard (TV), no
      tilled grassed vineyard (GV), former vineyards (FV), hay crop and pasture (HC and
      PA), cork oak forest (CO). Significant differences among ecosystems were found in
      most cases in (SOC), the related pools (total extractable carbon, humic and
      fulvic acids, not humified, not extractable), humification parameters (degree,
      rate and index of humification), and soil microbial activity (microbial carbon,
      respiration, metabolic quotient, and mineralization quotient). Pasture and cork
      oak forest showed in average a better soil quality for most biochemical and
      microbial parameters in comparison with the other ecosystems. The index of soil
      biological fertility (BFI) was higher under cork oak forest which is supposed to
      be the most sustainable ecosystem in the long term in this environment, able to
      maintain soil biological fertility and microbial diversity.

PMID- 28499228
TI  - Imprisoned in the Cretan mountains: How relict Zelkova abelicea (Ulmaceae) trees
      cope with Mediterranean climate.
AB  - We investigate the sensitivity of the relict, endemic Cretan tree species Zelkova
      abelicea (Lam.) Boiss. (Ulmaceae) to several climate variables (temperature,
      precipitation and drought). For this purpose, we establish the first centennial
      tree-ring chronology for the species, and the first ever tree-ring chronology for
      a broadleaved species on Crete. We demonstrate the strong sensitivity of Z.
      abelicea towards precipitation and drought in late spring to early summer and the
      absence of a significant response to abundant precipitation occurring during
      winter or early spring. Whereas the late spring sensitivity is strong and
      consistent through time, the species seems to be experiencing a loss of signal
      towards early summer conditions since the 1970s, interpreted as an earlier
      cessation of cambial activity due to the increase in summer drought conditions on
      Crete. However, despite a reduced vegetative period, no significant decrease in
      radial growth of Z. abelicea was observed in the tree-ring series for the last
      decades, thus highlighting the capacity of Z. abelicea to withstand changing
      environmental conditions.

PMID- 28499229
TI  - Operational integration of time dependent toxicity impact category in dynamic
      LCA.
AB  - Life Cycle Assessment (LCA) is the most widely used method for the environmental
      evaluation of an anthropogenic system and its capabilities no longer need to be
      proved. However, several limitations have been pointed out by LCA scholars,
      including the lack of a temporal dimension. The objective of this study is to
      develop a dynamic approach for calculating the time dependent impacts of human
      toxicity and ecotoxicity within LCA. A new framework is proposed, which includes
      dynamic inventory and dynamic impact assessment. This study focuses on the
      dynamic fate model for substances in the environment, combined with the USEtox(r)
      model for toxicity assessment. The method takes into account the noisy and random
      nature of substance emissions in function of time, as in the real world, and uses
      a robust solver for the dynamic fate model resolution. No characterization
      factors are calculated. Instead, a current toxicity is calculated as a function
      of time i.e. the damage produced per unit of time, together with a time dependent
      cumulated toxicity, i.e. the total damage produced from time zero to a given time
      horizon. The latter can be compared with the results obtained by the conventional
      USEtox(r) method: their results converge for a very large time horizon
      (theoretically at infinity). Organic substances are found to disappear relatively
      rapidly from the environmental compartments (in the time period in which the
      emissions occur) while inorganic substances (i.e. metals) tend to persist far
      beyond the emission period.

PMID- 28499230
TI  - Species complexes within epiphytic diatoms and their relevance for the
      bioindication of trophic status.
AB  - The popularity of aquatic bioassessments has increased in Europe and worldwide,
      with a considerable number of methods being based on benthic diatoms. Recent
      evidence from molecular data and mating experiments has shown that some
      traditional diatom morphospecies represent species complexes, containing several
      to many cryptic species. This case study is based on epiphytic diatom and
      environmental data from shallow fishponds, investigating whether the recognition
      and use of fine taxonomic resolution (cryptic species) can improve assessment of
      community response to environmental drivers and increase sharpness of
      classification, compared to coarse taxonomic resolution (genus level and species
      level with unresolved species complexes). Secondly, trophy bioindication based on
      a species matrix divided into two compartments (species complexes and remaining
      species) was evaluated against the expectation that species complexes would be
      poor trophy indicators, due to their expected wide ecological amplitude. Finally,
      the response of species complexes and their members (cryptic species) to a
      trophic gradient (phosphorus) were compared. Multivariate analyses showed similar
      efficiency of all three taxonomic resolutions in depicting community patterns and
      their environmental correlates, suggesting that even genus level resolution is
      sufficient for routine bioassessment of shallow fishponds with a wide trophic
      range. However, after controlling for coarse taxonomic matrices, fine taxonomic
      resolution (with resolved cryptic species) still showed sufficient variance
      related to the environmental variable (habitat groups), and increased the
      sharpness of classification, number of indicator species for habitat categories,
      and gave better separation of habitat categories in the ordination space.
      Regression analysis of trophic bioindication and phosphorus concentration showed
      a weak relationship for species complexes but a close relationship for the
      remaining taxa. GLM models also showed that no species complex responded to
      phosphorus concentration. It follows that the studied species complexes have wide
      tolerances to, and no apparent optima for, phosphorus concentrations. In
      contrast, various responses (linear, unimodal, or no response) of cryptic species
      within species complexes were found to total phosphorus concentration. In some
      cases, fine taxonomic resolution to species level including cryptic species has
      the potential to improve data interpretation and extrapolation, supporting recent
      views of species surrogacy.

PMID- 28499231
TI  - Radiofrequency electromagnetic fields and some cancers of unknown etiology: An
      ecological study.
AB  - Simultaneously with the increase of Radiofrequency Electromagnetic Fields (RF
      EMF) in recent decades, there has been increasing concern about their potential
      relation with the etiology of several tumors. At this time, the techniques of
      spatial data analysis jointly with the study of the personal exposure to these
      fields offer a new approach to the problem. This paper presents the results of a
      preliminary epidemiological study, combining Epidemiology, Statistics and
      Geographical Information Systems (GIS), in which we analyzed the correlation
      between exposure to RF-EMF in the city of Albacete (166,000 inhabitants,
      southeast Spain) and the incidence of several cancers with unspecific causes
      (lymphomas, and brain tumors). We used statistical tools to analyze the spatial
      point patterns and aggregate data with the aim to study the spatial randomness
      and to determine the zones with the highest incidence from 95 tumors studied (65
      lymphomas, 12 gliomas and 18 meningiomas). We also perform a correlation
      (Spearman) study between the personal exposure to RF-EMF in 14 frequency bands,
      recorded by an EME Spy 140 (Satimo) exposimeter in the city's administrative
      regions, and the incidence of the tumors registered from January 2012 to May
      2015. The studied cancer cases have a random spatial distribution inside the
      city. On the other hand, and by means of an ecological study, we verified that
      the exposure to RF-EMF registered in the city of Albacete shows little
      correlation with the incidence of the studied tumors (gliomas (rho=0.15),
      meningiomas (rho=0.19) and lymphomas (rho=-0.03)). The proposed methodology
      inaugurates an unexplored analysis path in this field.

PMID- 28499232
TI  - Co-application of sewage sludge with biochar increases disappearance of
      polycyclic aromatic hydrocarbons from fertilized soil in long term field
      experiment.
AB  - The application of sewage sludge with biochar as fertilizer may be a new method
      improves soil properties. Biochar increases of the crops productivity and
      reduction of bioavailability of contaminants. In the present study the
      persistence of sum of 16 (Sigma16) PAHs (US EPA 16 PAHs) in a sewage sludge
      amended soil (11t/h) and in a sewage sludge-amended soil with the addition of
      biochar (at a rate of 2.5, 5 or 10% of sewage sludge (dry weight basis)) was
      determined. This study was carried out as a plot experiment over a period of
      18months. Samples for analysis were taken at the beginning of the study and after
      6, 12 and 18months from the beginning of the experiment. Application of sewage
      sludge as a soil amendment did not cause a significant change (P>=0.05) in the
      soil content of Sigma16 PAHs. In turn, the addition of biochar with sewage sludge
      to the soil, regardless of the contribution of biochar in the sewage sludge,
      resulted in a significant decrease in PAH content already at the beginning of the
      experiment. Throughout the experiment, in all treatments the PAH content varied,
      predominantly showing a decreasing trend. Ultimately, after 18months the content
      of Sigma16 PAHs decreased by 19% in the experiment with sewage sludge alone and
      by 45, 35 and 28% in the experiment with sewage sludge and the 2.5%, 5.0% and 10%
      biochar rates, respectively. After 18months of the study, the largest losses in
      the sewage sludge-amended soil were observed for 2- and 3-ring PAHs. In the
      sewage sludge- and biochar-amended soil, compared to the beginning of the study
      and the sewage sludge-amended soil, the highest losses were found for 5- and 6
      ring PAHs (2.5 and 5.0% rates) as well as for 5- and 2-ring PAHs (10% rate).

PMID- 28499233
TI  - Multi-scale sustainability assessments for biomass-based and coal-based fuels in
      China.
AB  - Transportation liquid fuels production is heavily depend on oil. In recent years,
      developing biomass based and coal based fuels are regarded as promising
      alternatives for non-petroleum based fuels in China. With the rapid growth of
      constructing and planning b biomass based and coal based fuels production
      projects, sustainability assessments are needed to simultaneously consider the
      resource, the economic, and the environmental factors. This paper performs multi
      scale analyses on the biomass based and coal based fuels in China. The production
      cost, life cycle cost, and ecological life cycle cost (ELCC) of these synfuels
      are investigated to compare their pros to cons and reveal the sustainability. The
      results show that BTL fuels has high production cost. It lacks of economic
      attractiveness. However, insignificant resource cost and environmental cost lead
      to a substantially lower ELCC, which may indicate better ecological
      sustainability. CTL fuels, on the contrary, is lower in production cost and
      reliable for economic benefit. But its coal consumption and pollutant emissions
      are both serious, leading to overwhelming resource cost and environmental cost. A
      shifting from petroleum to CTL fuels could double the ELCC, posing great threat
      to the sustainability of the entire fuels industry.

PMID- 28499234
TI  - Magnetic implants in the tongue for assistive technologies: Tests of migration;
      oromotor function; and tissue response in miniature pigs.
AB  - OBJECTIVE: Uncertain biological consequences of titanium-magnet (Ti-mag) tongue
      implants constrain application of the Tongue Drive System (TDS), a brain-tongue
      computer interface for individuals with severe physical impairment. Here we
      describe oromotor function and tongue tissue response following Ti-Mag
      implantation and explantation in the miniature pig, an animal model with a tongue
      similar in size to humans. DESIGN: A 1.8*6.2mm Ti-mag tracer was implanted into
      the anterior tongue in five Yucatan minipigs. X-rays were taken immediately and
      >six days after implantation to evaluate tracer migration. In three minipigs, the
      tracer was explanted >16days after implantation. Twenty-five days post
      explantation, tongue tissue was harvested and processed for histological and
      immunohistochemical (IHC) markers of healing. In two minipigs tissue markers of
      healing were evaluated post-mortem following >12days implantation. Drink cycle
      rate (DCR) was characterized to determine the impact of procedures on oromotor
      function. RESULTS: Neither implantation (N=5) nor explantation (N=3) changed DCR.
      X-rays revealed minimal tracer migration (N=4, 0-4mm). By histology and IHC a
      robust capsule was present two weeks post-implantation with limited fibrosis.
      Explantation produced localized fibrosis and limited muscle remodeling.
      CONCLUSIONS: These findings suggest the safety of Ti-mag anterior tongue implants
      for assistive technologies in humans.

PMID- 28499235
TI  - Probiotics: A non-conventional therapy for oral lichen planus.
AB  - Oral lichen planus (OLP) is a common T-cell mediated chronic inflammatory
      disease. Although the etiology is still unclear, present studies suggest that the
      composition of the oral microbiota and psychological problems are implicated in
      the etiology of OLP. The pathogenesis of OLP includes mainly antigen-specific and
      non-specific mechanisms. Antigen-specific mechanisms involve T-cell activation
      following antigen presentation and apoptosis of basal keratinocytes triggered by
      CD8+ cytotoxic T cells, while non-specific mechanisms consist of matrix
      metalloproteinase over-expression and mast cell degranulation in OLP lesions.
      Therapies for OLP are mainly used to control symptoms and a specific cure is not
      yet available. Probiotics are capable of modulating the immune response in a
      strain-specific manner. They are able to alleviate microbial infection and
      suppress T-cell activation, infiltration and proliferation, as well as suppress
      keratinocyte apoptosis and nuclear factor-kappa B signaling. Furthermore,
      probiotics can also modulate the production of inflammatory cytokines and
      microRNAs, inhibit MMP-9 expression and mast cell degranulation, and ameliorate
      psychological problems, all of which are involved in the pathogenesis of OLP.
      Therefore, we hypothesize that probiotics may be applicable to OLP as a safe,
      inexpensive and non-conventional therapy.

PMID- 28499236
TI  - Putative periodontal pathogens in the subgingival plaque of Sudanese subjects
      with aggressive periodontitis.
AB  - BACKGROUND AND OBJECTIVES: There has been limited study of the bacterial species
      associated with aggressive periodontitis (AgP) in high-risk populations in
      Africa. The aim of this study was to investigate and quantify the presence of
      four putative periodontal pathogens in the subgingival plaque of Sudanese
      subjects with AgP. A secondary aim was to investigate the effect of varying the
      detection threshold on the reported prevalence of the bacterial species
      investigated. MATERIALS AND METHODS: Subgingival plaque samples were collected
      from AgP cases (n=73) and healthy controls (n=71). Bacterial DNA was extracted
      and analyzed by quantitative polymerase chain reaction for the detection and
      quantification of four putative periodontal pathogens: Porphyromonas gingivalis,
      Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella
      forsythia. RESULTS: At the lowest detection threshold (>101 cells), P. gingivalis
      (p<0.0001) was more prevalent in AgP cases than controls. T. forsythia and T.
      denticola had a high prevalence (>70%) in AgP cases at all detection levels.
      While T. forsythia was significantly more frequently identified in AgP than in
      controls at all detection thresholds, this was only the case for T. denticola at
      the intermediate threshold (>102 cells). A. actinomycetemcomitans was identified
      less frequently than the other bacterial species with no difference in its
      prevalence between AgP cases and controls. CONCLUSION: The prevalence of the
      putative periodontal pathogens investigated varied considerably in Sudanese
      subjects with AgP and in periodontally healthy controls depending on the
      detection thresholds applied. T. forsythia was identified as having the strongest
      association with AgP.

PMID- 28499237
TI  - The protective effect of propofol against TNF-alpha-induced apoptosis was
      mediated via inhibiting iNOS/NO production and maintaining intracellular Ca2+
      homeostasis in mouse hippocampal HT22 cells.
AB  - AIM: Inflammation cytokine tumor necrosis factor-alpha (TNF-alpha) induces
      apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF
      alpha-induced apoptosis in mouse hippocampal HT22 cells and aimed to explore the
      underlying mechanisms. METHODS: Mouse hippocampal HT22 cells were pretreated with
      propofol, and then stimulated with TNF-alpha. Cell viability was measured by cell
      counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis.
      The effect of propofol on TNF-alpha-modulated nitric oxide production was
      measured by a nitrate reductase assay kit, intracellular calcium release and
      mitochondrial membrane potential (MMP) depolarization were measured by flow
      cytometry analysis, and the expression of inducible nitric oxide synthase (iNOS),
      C/EBP homologous protein (CHOP), B-cell lymphoma 2 (Bcl2) family and caspases
      were detected by Western blot. RESULTS: Compared with control, TNF-alpha
      concentration- and time-dependently increased HT22 cell apoptosis, which was
      attenuated by 25MUmol/l propofol. TNF-alpha (40ng/ml, 24h) induced the
      overexpression of iNOS and the release of nitric oxide, caused the accumulation
      of intracellular Ca2+ and endoplasmic reticulum (ER) stress, and therefore
      leading to mitochondrial dysfunction. Importantly, these effects were alleviated
      by 25MUmol/l propofol. CONCLUSIONS: We demonstrated that propofol could attenuate
      TNF-alpha-induced HT22 apoptosis. More importantly, we indicated that the
      underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.

PMID- 28499238
TI  - Inhibition of iNOS protects cardiomyocytes against coxsackievirus B3-induced cell
      injury by suppressing autophagy.
AB  - BACKGROUND: Coxsackievirus B3 (CVB3), a member of the picornavirus family, is one
      of the major causative enteroviruses of viral myocarditis. The aim of the current
      study was to investigate the role and underlying mechanism of iNOS and autophagy
      in CVB3 infected cardiomyocytes. METHODS: Myocardial cell H9c2 were randomly
      divided into four groups: control group, CVB3 group, CVB3+L-NAME group and the
      CVB3+iNOS siRNA group. Cell proliferation was detected by MTT method and cell
      apoptosis was determined by flow cytometric. The protein expression levels were
      determined by Western blot. Anisomycin was used to activate JNK pathway in CVB3
      infected H9c2 cells. RESULTS: The results demonstrated that the inhibition of
      iNOS significantly elevated cell proliferation and suppressed cell apoptosis of
      CVB3-induced H9c2 cells. The production of MDA was obviously decreased, while the
      activity of SOD was increased by the addition of L-NAME or iNOS siRNA compared
      with the CVB3 group. Expression of the autophagy marker proteins LC3 II and
      Beclin 1 was significantly decreased, and the autophagy substrate p62 was
      dramatically increased in iNOS inhibition groups compared with the CVB3 group.
      Moreover, iNOS inhibition suppressed the JNK pathway in CVB3-infected H9c2 cells.
      Furthermore, administration of the JNK pathway stimulator, anisomycin,
      counteracted the effect of iNOS inhibition in CVB3-infected H9c2 cells.
      CONCLUSION: The inhibition of iNOS protects cardiomyocytes against CVB3-induced
      cell injury by regulating autophagy and the JNK pathway, which may provide a
      novel therapeutic strategy for treating CVB3-induced myocarditis.

PMID- 28499239
TI  - Effect of recombinant human endostatin on hypertrophic scar fibroblast apoptosis
      in a rabbit ear model.
AB  - Hypertrophic scar (HS) is a dermal fibroproliferative disorder characterized by
      the excessive proliferation of fibroblasts and is thought to result from a
      cellular imbalance caused by the increased growth and reduced apoptosis of
      hypertrophic scar fibroblasts (HSFs). Our recent study demonstrated that
      recombinant human endostatin (rhEndostatin) plays a key role in the inhibition of
      HSF proliferation in vitro, with a resulting decrease in dermal thickness and
      scar hypertrophy. However, the effect of this protein on HSF apoptosis is
      unknown. The present study was undertaken to directly examine the effect of
      rhEndostatin on HSF apoptosis in the rabbit ear model. Transmission electron
      microscopy and flow cytometry were used to investigate HSF apoptosis in scar
      tissues and cultured HSFs in vitro, respectively. The expression levels of the c
      jun, c-fos, NF-kappaB, fas, caspase-3, and bcl-2 gene products in HSFs were
      quantified using real-time PCR and Western blotting assays. Our data reveal that
      rhEndostatin (2.5 or 5mg/ml) induces HSF apoptotic cell death in scar tissue.
      Additionally, HSFs treated with rhEndostatin (100mg/L) in vitro accumulated in
      early and late apoptosis and displayed significantly decreased expression of c
      jun, c-fos, NF-kappaB, fas, caspase-3 and bcl-2. In sum, these results
      demonstrate that rhEndostatin induces HSF apoptosis, and this phenotypeis
      partially due to downregulation of NF-kappaB and bcl-2. These findings suggest
      that rhEndostatin may have an inhibitory effect on scar hypertrophy in vivo via
      HSF apoptotic induction and therefore has potential therapeutic use for the
      treatment of HS.

PMID- 28499240
TI  - Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome
      (CP/CPPS) induced by immunization with a novel peptide T2.
AB  - BACKGROUND: The exact etiological mechanism of Chronic Prostatitis/chronic pelvic
      pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid
      theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain
      syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be
      beneficial in elucidating mechanisms involved in the pathogenesis of Chronic
      Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). METHODS: 40 male Sprague
      Dawley rats with an average weight of 180-220g were equally distributed into five
      groups. The normal control group was injected with normal saline (.9% NACL), the
      CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a
      novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA.
      Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin
      staining and Immunohistochemistry were used to investigate inflammatory cell
      infiltration and IL-1beta in the prostate tissue respectively. ELISA technique
      was used to measure the serum level of CRP and TNF-alpha. T-test was used to
      analyze the results. RESULTS: Maximum infiltration of inflammatory cells and the
      highest level of IL-1beta in the prostate tissue was observed in T2+AL(OH)3+CFA
      group as revealed by histopathology and Immunohistochemistry, respectively.
      Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-alpha and
      CRP as determined by ELISA technique. CONCLUSION: Our results demonstrated that
      T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We
      believe that our present model will be highly beneficial for investigation of the
      pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

PMID- 28499241
TI  - Pathophysiology, mechanisms and applications of mesenchymal stem cells for the
      treatment of spinal cord injury.
AB  - Spinal Cord Injury (SCI) is a serious devastating condition associated to the
      high chances of morbidity and mortality. It involves a primary and a secondary
      injury, former cause damages to both lower and upper motor neurones and disrupts
      sensory, motor and autonomic functions while the latter involves various stages
      of molecular plus cellular incidents which elaborate the original injury. In the
      treatment of SCI, stem cells possess a good therapeutic potential. Bone marrow,
      adipose tissue, placenta, amniotic fluid and umbilical cord are the good sources
      for mesenchymal stem cells. This review article shows the uses of bone marrow
      derived mesenchymal cells in the treatment of acute and chronic case of SCI and
      its future scope.

PMID- 28499242
TI  - Potential ameliorative effects of grape seed-derived polyphenols against cadmium
      induced prostatic deficits.
AB  - Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study,
      rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium
      chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived
      polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic
      levels of E-cadherin, fibronectin, and alpha-smooth muscle actin were measured by
      immunohistochemical and qPCR analysis. The oxidative stress was measured by
      detecting the levels of malondialdehyde, nitric oxide, reduced
      glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally,
      the prostatic expressions of transforming growth factor-beta1 (TGF-beta1), type I
      TGF-beta receptor (TGF-betaRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7,
      nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and gamma-glutamate
      cysteine ligase catalytic subunit (gamma-GCLC) were measured by western blot. The
      levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP
      ameliorated the prostatic oxidative stress and fibrosis induced by CdCl2. GSP
      also inhibited the over-generation of TGF-beta1 and p-Smad3, as well as enhanced
      the levels of Smad7, Nrf-2, HO-1, gamma-GCLC and miR-133a/b. These results showed
      that GSP could attenuate Cd-induced prostatic deficits.

PMID- 28499244
TI  - MicroRNA-24-1 suppresses mouse hepatoma cell invasion and metastasis via directly
      targeting O-GlcNAc transferase.
AB  - MicroRNAs (miRNAs) are endogenous non-coding regulatory RNAs involved in multiple
      cellular processes. Emerging evidences showed that miRNAs are involved in
      changing the cell surface glycosylation modification and oncogenesis. In this
      study, the role of miRNA-24-1 in O-GlcNAcylation and metastasis of mouse
      hepatocarcinoma cells was investigated. miRNAs expression array profiles were
      obtained from mouse hepatocarcinoma cell lines Hca-P and Hca-F with the low/high
      lymphatic metastasis potential, respectively. Based on the miRNAs expression
      array profiles, miRNA-24-1 expression was found to exhibit converse coincidence
      with metastasis potential, O-GlcNAc transferase (OGT) expression and O
      GlcNAcylation. Dual-luciferase reporter assay revealed that miRNA-24-1
      specifically binds to 3'-UTR of OGT. Furthermore, transfecting mouse
      hepatocarcinoma cells with miR-24-1 mimic and antisense oligonucleotide showed
      miR-24-mediates OGT expression silencing. This silencing is associated with the
      suppression of cell metastasis potential, down-regulation of the O-GlcNAcylation
      on c-Myc and decrease of c-Myc expression at the protein level rather than the
      mRNA level. Collectively, these results suggested that as a tumor suppressor, miR
      24-1 may regulate mouse hepatocarcinoma cells migration and invasion, at least
      partially through targeting OGT, which could regulate the O-GlcNAcylation and the
      stability of this oncoprotein c-Myc. This may give insight into a novel mechanism
      and therapy of tumor lymphatic metastasis.

PMID- 28499243
TI  - Diospyros, an under-utilized, multi-purpose plant genus: A review.
AB  - The genus Diospyros from family Ebenaceae has versatile uses including edible
      fruits, valuable timber, and ornamental uses. The plant parts of numerous species
      have been in use as remedies in various folk healing practices, which include
      therapy for hemorrhage, incontinence, insomnia, hiccough, diarrhea etc.
      Phytochemical constituents such as terpenoids, ursanes, lupanes, polyphenols,
      tannins, hydrocarbons, and lipids, benzopyrones, naphthoquinones, oleananes, and
      taraxeranes have been isolated from different species of this genus. The
      biological activities of these plants such as antioxidant, anti-inflammatory,
      analgesic, antipyretic, anti-diabetic, antibacterial, anthelmintic,
      antihypertensive, cosmeceutical, enzyme-inhibitory etc. have been validated by
      means of an in vitro, in vivo, and clinical tests. As a rich reserve of
      pharmacologically important components, this genus can accelerate the pace of
      drug discovery. Accordingly, the aim of the present review is to survey and
      summarize the recent literature pertaining to the medicinal and pharmacological
      uses of Diospyros, and to select experimental evidence on the pharmacological
      properties of this genus. In addition, the review also aims at identifying areas
      that need development to make use of this genus, especially its fruit and
      phytochemicals as means for economic development and for drug discovery.

PMID- 28499245
TI  - Anti-hyperalgesic effect of Lippia grata leaf essential oil complexed with beta
      cyclodextrin in a chronic musculoskeletal pain animal model: Complemented with a
      molecular docking and antioxidant screening.
AB  - BACKGROUND: Due to its unclear pathophysiology, the pharmacological treatment of
      fibromyalgia is a challenge for researchers. Studies using medicinal plants, such
      as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown
      innovative results. OBJECTIVE: The present research intended to evaluate the
      effect of an inclusion complex containing beta-cyclodextrin (betaCD) inclusion
      complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain
      model, its central activity and its possible interaction with neurotransmitters
      involved in pain. METHODS: After acid saline-induced chronic muscle pain, male
      mice were evaluated for primary and secondary hyperalgesia and muscle strength.
      Moreover, an antagonist assay was performed to assess the possible involvement of
      the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos
      protein in the spinal cord was assessed, and a docking study and antioxidant
      assays were performed. RESULTS: The treatment with LG-betaCD, especially in the
      dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal
      and muscle threshold. Furthermore, LG-betaCD was shown to affect the opioidergic
      and serotonergic pathways. There were no significant changes in muscle strength.
      Fos protein immunofluorescence showed a significant decrease in expression in the
      dorsal horn of the spinal cord. The main compounds of LG showed through the
      docking study interaction energies with the alpha-adrenergic and MUOpioid
      receptors. In all antioxidant assays, LG exhibited stronger antioxidant
      activities than LG-betaCD. CONCLUSION: This study suggested that LG-betaCD could
      be considered as a valuable source for designing new drugs in the treatment of
      chronic pain, especially musculoskeletal pain.

PMID- 28499246
TI  - Evaluation of the therapeutic effects of lateral approach combined with
      anteromedial approach in the treatment of terrible triad of the elbow.
AB  - OBJECTIVE: This study aims to evaluate the therapeutic effects of the lateral
      approach combined with anteromedial approach in the treatment of terrible triad
      of the elbow. METHODS: Between June 2010 and January 2015, 334 patients suffering
      from terrible triad of the elbow, amongst whom 105 cases underwent lateral
      approaches combined with anteromedial approaches, 112 cases underwent lateral
      approaches, and 117 cases underwent anteromedial approaches were included in the
      study. The serum levels of C-reactive protein (CRP), interleukin-6 (IL-6),
      interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were detected
      using enzyme-linked immunosorbent assay (ELISA) before operation and at 7 days
      and 3 months after operation. X-ray imaging was employed to examine the recovery
      condition of the elbow, and the joint motion and the forearm rotation of elbow
      were evaluated before and after the operation. RESULTS: Excellent rate was
      obtained in accordance with the Mayo Elbow Performance Score (MEPS). The serum
      levels of CRP, IL-6, IL-8 and TNF-alpha gradually decreased to normal levels
      after the operation, and recovery was faster in patients undergoing lateral
      approach combined with anteromedial approach in comparison to those undergoing
      lateral and anteromedial approaches. The X-ray images showed good recovery of
      elbows in all patients, but the range of joint motion, forearm rotation degree,
      and MEPS were higher in patients undergoing lateral approach combined with
      anteromedial approach compared to those undergoing lateral and anteromedial
      approaches independently. CONCLUSION: Taken together, these findings demonstrate
      lateral approach combined with anteromedial approach reveals better therapeutic
      effect than lateral approach and anteromedial approach in the treatment of
      terrible triad of the elbow.

PMID- 28499247
TI  - NLRC5 deficiency promotes myocardial damage induced by high fat diet in mice
      through activating TLR4/NF-kappaB.
AB  - The metabolic syndrome could be induced by high fat diet, leading to
      cardiovascular diseases, such as myocardial damage. Inflammation response and
      oxidative stress have been reported to be involved in high fat-induced heart
      injury, and the molecular mechanism is not fully understood. The NOD-like protein
      family member, NLRC5, could interact with IKKalpha to inhibit IKK complex
      activation. In our study, high fat diet-feeding mice showed cardiac fibrosis,
      inflammation and oxidative stress through collagen accumulation, TLR4/NF-kappaB
      and MAPKs signaling pathways activation. NLRC5 knockout mice fed with high fat
      showed accelerated fibrosis and inflammation response by promoting alpha-SMA,
      Collagen I, Collagen III, TLR4/MyD88, phosphorylated IKKalpha, IkappaBalpha and
      NF-kappaB expression. And no effect on oxidative stress was observed in wild type
      and NLRC5-deficiency samples in in vivo studies. Moreover, NLRC5-knockout and 
      knockdown cardiac muscle cells challenged with LPS also exhibited aggravated
      fibrosis levels and inflammatory response without any influences on ROS
      production in in vitro studies. In conclusion, the findings indicated that NLRC5
      showed important effects on high fat-induced heart injury via fibrosis and
      inflammation modulation, providing an essential target for improving myocardial
      damage induced by high fat diet.

PMID- 28499248
TI  - Influence of fertilisation with sewage sludge-derived preparation on selected
      soil properties and prairie cordgrass yield.
AB  - The aim of the study was to evaluate the effect of using a fertilizer obtained
      from waste substances on selected physical and chemical properties of soil and
      biomass yield Spartina pectinate. The fertilizer used for soil (C) fertilisation
      contained sewage sludge (SS), waste soil fractions of brown coal (BC), brown coal
      ash (BCA) enriched with mineral potassium (K) fertilizer (C+SS+BC+BCA+K). The
      composition of the preparation was developed by the authors and adjusted to the
      quality of the fertilised soil and the individual characteristics of the plant.
      It was assumed that the preparation should replace expensive conventional
      fertilisation methods, allow for management of waste substances and improve soil
      properties, leading to a high yield of Spartina pectinata used as energy crop.
      The plants were grown on the soil from the Huta Czestochowa steelworks effect
      zone. The soil was light, with acid reaction (pH KCl =5.5), with small contents
      of such contaminants as Cd and Zn and elevated Pb content. Based on a three-year
      pot experiment, the paper presents the results of the examinations concerning the
      effect of fertilisation on soil pH, hydrolytic acidity, sorptive properties,
      content of humic acids, organic coal and total nitrogen in soil and crop
      yielding. The effect of the use of the fertilizer (C+SS+BC+BCA+K) was compared
      with the use of the sludge (C+SS), sludge with mineral fertilizers (C+SS+NPK),
      mixture of brown coal and mineral fertilizers (C+BC+NPK) and effect of only
      mineral fertilizers (C+NPK). Fertilisation with (C+SS+BC+BCA+K) led to the
      increase in soil pH from 5.5 to 6.0, which is considered sufficient for light
      soils. The fertilised soil was characterized by sorption capacity of ca. 5.8
      cmol(+)/kg, and, after fertilisation with O+W+P, reached the value of ca. 8.0
      cmol(+)kg-1. Consequently the soil can be regarded as of good quality in terms of
      its capability to store nutrients. The C:N ratio was also extended from 11:1
      (control soil) to 14:1 (C+SS+BC+BCA+K). The yield of Spartina pectinata in the
      first year was 1.6 and in the third year 2.7 times higher in the case of
      fertilisation with the investigated mixture as compared to the control.

PMID- 28499249
TI  - Estimates of potential childhood lead exposure from contaminated soil using the
      US EPA IEUBK Model in Sydney, Australia.
AB  - Surface soils in portions of the Sydney (New South Wales, Australia) urban area
      are contaminated with lead (Pb) primarily from past use of Pb in gasoline, the
      deterioration of exterior lead-based paints, and industrial activities. Surface
      soil samples (n=341) were collected from a depth of 0-2.5cm at a density of
      approximately one sample per square kilometre within the Sydney estuary catchment
      and analysed for lead. The bioaccessibility of soil Pb was analysed in 18
      samples. The blood lead level (BLL) of a hypothetical 24 month old child was
      predicted at soil sampling sites in residential and open land use using the
      United States Environmental Protection Agency (US EPA) Integrated Exposure Uptake
      and Biokinetic (IEUBK) model. Other environmental exposures used the Australian
      National Environmental Protection Measure (NEPM) default values. The IEUBK model
      predicted a geometric mean BLL of 2.0+/-2.1ug/dL using measured soil lead
      bioavailability measurements (bioavailability =34%) and 2.4+/-2.8ug/dL using the
      Australian NEPM default assumption (bioavailability =50%). Assuming children were
      present and residing at the sampling locations, the IEUBK model incorporating
      soil Pb bioavailability predicted that 5.6% of the children at the sampling
      locations could potentially have BLLs exceeding 5ug/dL and 2.1% potentially could
      have BLLs exceeding 10ug/dL. These estimations are consistent with BLLs
      previously measured in children in Sydney.

PMID- 28499252
TI  - Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced
      pro-inflammatory responses in astrocytes.
AB  - Histone deacetylase 6 (HDAC6) likely is important in inflammatory diseases.
      However, how HDAC6 exerts its effect on inflammatory processes remains unclear.
      HIV-1 transactivator of transcription (Tat) activates NADPH oxidase resulting in
      generation of reactive oxygen species (ROS), leading to extensive neuro
      inflammation in the central nervous system. We investigated the correlation of
      HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown
      attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6
      knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such
      as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A
      suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N
      acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced
      expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10.
      Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent
      expression of chemokines. The collective results point to the potential crosstalk
      between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for
      relief of HIV-1 Tat-mediated neuro-inflammation.

PMID- 28499251
TI  - Sequestration of polyunsaturated fatty acids in membrane phospholipids of
      Caenorhabditis elegans dauer larva attenuates eicosanoid biosynthesis for
      prolonged survival.
AB  - Mechanistic basis governing the extreme longevity and developmental quiescence of
      dauer juvenile, a "non-ageing" developmental variant of Caenorhabditis elegans,
      has remained largely obscure. Using a lipidomic approach comprising multiple
      reaction monitoring transitions specific to distinct fatty acyl moieties, we
      demonstrated that in comparison to other developmental stages, the membrane
      phospholipids of dauer larva contain a unique enrichment of polyunsaturated fatty
      acids (PUFAs). Esterified PUFAs in phospholipids exhibited temporal accumulation
      throughout the course of dauer endurance, followed by sharp reductions prior to
      termination of diapause. Reductions in esterified PUFAs were accompanied by
      concomitant increases in unbound PUFAs, as well as their corresponding downstream
      oxidized derivatives (i.e. eicosanoids). Global phospholipidomics has unveiled
      that PUFA sequestration in membrane phospholipids denotes an essential aspect of
      dauer dormancy, principally via suppression of eicosanoid production; and a
      failure to upkeep membrane lipid homeostasis is associated with termination of
      dauer endurance.

PMID- 28499250
TI  - Redox regulation of microRNAs in endometriosis-associated pain.
AB  - Endometriosis is a chronic, painful condition with unknown etiology. A
      differential expression of microRNAs in the endometriotic tissues from women with
      endometriosis with pain compared to those without suggested a plausible role for
      miRNA or epigenetic mechanisms in the etiology of endometriotic pain. The
      peritoneal milieu is involved in maintenance of endometriotic lesion and
      nociception. We recently showed the mechanistic role for oxidized-lipoproteins
      (ox-LDLs) present in peritoneal fluid (PF) in endometriosis and pain. We explored
      the possibility of ox-LDLs modulating the expression of miRNAs in a manner
      similar to PF from women with endometriosis. Expression levels of miRNAs and
      their predicted nociceptive and inflammatory targets were determined in PF and ox
      LDL treated human endometrial cell-lines. Samples from IRB-approved and consented
      patients with and without endometriosis or pain were used. These were compared to
      endometrial cell-lines treated with various forms of oxidized-lipoproteins. RNA
      (including miRNAs) were isolated from treated endometrial cells and expression
      levels were determined using commercial miRNome arrays. Cell lysates were used in
      immunoblotting for inflammatory proteins using a protein array. Twenty miRNAs
      including isoforms of miR-29, miR-181 and let-7 were mutually differentially
      expressed in cells treated with PF from endometriosis patients with pain and
      those treated with ox-LDL components. The ox-LDLs and endo-PF treatment also
      produced significant overexpression of microRNA predicted target genes nerve
      growth factor, interleukin-6 and prostaglandin E synthase and overexpression of
      their downstream protein targets Mip1alpha and MCP1. This study showed
      similarities between miRNA regulation in PF from endometriotic women and ox-LDLs
      present in abundance in the PF of these women. Key miRNAs responsible for
      targeting nociceptive and inflammatory molecules were downregulated in the
      presence of ox-LDLs and endo-PF, thus playing a role in the etiology of
      endometriotic pain. These redox-sensitive miRNAs can be of potential use as
      targets in the treatment of endometriosis-associated pain.

PMID- 28499254
TI  - Improving xylose utilization of defatted rice bran for nisin production by
      overexpression of a xylose transcriptional regulator in Lactococcus lactis.
AB  - Present investigation explores the potential of defatted rice bran (DRB) serving
      as sole carbon source and partial nitrogen source to support Lactococcus lactis
      growth and nisin production. To retain the nutrients in DRB, especially protein
      fractions, thermal pretreatment followed by enzymatic hydrolysis without washing
      step was applied for saccharification. A maximum of 45.64g reducing sugar mainly
      containing 30.26g glucose and 5.66g xylose from 100g DRB was attained in
      hydrolysates of DRB (HD). A novel strategy of xylR (xylose transcriptional
      regulator) overexpression followed by evolutionary engineering was proposed,
      which significantly increased the capacity of L. lactis to metabolize xylose.
      Subsequently, RT-PCR results indicated that xylR overexpression stimulated
      expression of xylose assimilation genes synergistically with exposure to xylose.
      In HD medium, the highest nisin titer of the engineered strain FEXR was
      3824.53IU/mL, which was 1.37 times of that in sucrose medium by the original
      strain F44.

PMID- 28499253
TI  - The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and
      CaMKKbeta/AMPK pathways.
AB  - Age-related dysfunction of the central auditory system, known as central
      presbycusis, is characterized by defects in speech perception and sound
      localization. It is important to determine the pathogenesis of central
      presbycusis in order to explore a feasible and effective intervention method.
      Recent work has provided fascinating insight into the beneficial function of H2S
      on oxidative stress and stress-related disease. In this study, we investigated
      the pathogenesis of central presbycusis and tried to explore the mechanism of H2S
      action on different aspects of aging by utilizing a mimetic aging rat and
      senescent cellular model. Our results indicate that NaHS decreased oxidative
      stress and apoptosis levels in an aging model via CaMKKbeta and PI3K/AKT
      signaling pathways. Moreover, we found that NaHS restored the decreased activity
      of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro
      by regulating CaMKKbeta and PI3K/AKT. Mitochondria function was preserved by
      NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair
      enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated;
      mitochondrial membrane potential was restored; ATP production was increased; and
      mtDNA damage, indicated by the common deletion (CD), declined. These effects were
      also achieved by activating CaMKKbeta/AMPK and PI3K/AKT signaling pathways.
      Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS
      via CaMKKbeta and PI3K/AKT. Our findings demonstrate that the ability to resist
      oxidative stress and mitochondria function are both decreased as aging developed;
      however, NaHS, a novel free radical scavenger and mitochondrial protective agent,
      precludes the process of oxidative damage by activating CaMKKbeta and PI3K/AKT.
      This study might provide a therapeutic target for aging and age-related disease.

PMID- 28499255
TI  - Identification of an aspidospermine derivative from borage extract as an anti
      amyloid compound: A possible link between protein aggregation and antimalarial
      drugs.
AB  - A number of human diseases, including Alzheimer's and Parkinson's have been
      linked to amyloid formation. To search for an anti-amyloidogenic product,
      alkaloid enriched extract from borage leaves was examined for anti-amyloidogenic
      activity using Hen Egg White Lysozyme (HEWL) as a model protein. After isolation
      of the plant extract using rHPLC, only one fraction indicated a significant
      bioactivity. TEM analysis confirmed a remarkable reduction of amyloid fibrils in
      the presence of the bioactive fraction. To identify the effective substance in
      the fraction, mass spectrometry, FTIR, and NMR were performed. Our analyses
      determined that the bioactive compound as 1-acetyl-19,21-epoxy-15,16
      dimethoxyaspidospermidine-17-ol, a derivative of aspidospermine. To investigate
      the mechanism of the inhibition, ANS binding, intrinsic fluorescence, and amide I
      content were performed in the presence of the bioactive compound. All the results
      confirmed the role of the compound in assisting the proper folding of the
      protein. In addition, molecular docking indicated the aspidospermine derivative
      binds the amyloidogenic region of the protein. Our results show that the alkaloid
      extracted from borage leaves reduces protein aggregation mediating through
      structural elements of the protein, promoting the correct folding of lysozyme.
      Since a number of aspidospermine compounds have been shown to possess potent
      antimalarial activities, the action of compound identified in the present study
      suggests a possible link between protein aggregation and aspidospermine drugs.

PMID- 28499256
TI  - From common to rare Zingiberaceae plants - A metabolomics study using GC-MS.
AB  - Zingiberaceae plants, commonly known as gingers, have been popular for their
      medicinal and culinary uses since time immemorial. In spite of their numerous
      health-promoting applications, many Zingiberaceae plants still receive no
      scientific attention. Moreover, existing reports mostly focused only on the
      Zingiberaceae rhizomes. Here, untargeted metabolite profiling using Gas
      Chromatography - Mass Spectrometry (GC-MS) was used to compare the metabolic
      composition of leaves and rhizomes of the more common gingers, Zingiber
      officinale Rosc. (ZO), Curcuma longa L. (CL), and Etlingera elatior (Jack) R.M.
      Smith (EE), and the rare gingers, Amomum muricarpum Elmer (AM), Etlingera
      philippinensis (Ridl.) R.M. Smith (EP), and Hornstedtia conoidea Ridl. (HC).
      Principal component analysis (PCA) demonstrated that different species show
      substantial chemical differentiation and revealed potential markers among the
      different Zingiberaceae plants. Interestingly, the leaves of AM, CL, EE, EP, and
      HC had significantly higher levels of chlorogenic acid than ZO. Moreover,
      rhizomes of EP and HC were found to contain significantly higher levels of amino
      acids than ZO. Sugars and organic acids were generally less abundant in ZO leaves
      and rhizomes than in the other gingers. The leaves of EP and rhizomes of AM were
      found most similar to the leaves and rhizomes of common gingers, respectively.
      Results of this study provide significant baseline information on assessing the
      possible usage of the leaves of common gingers and further propagation and
      exploration of EP and AM. This study, being the first metabolomics report on rare
      plants such as AM, EP and HC, affirms the usefulness of untargeted metabolite
      profiling in exploring under-investigated plants.

PMID- 28499257
TI  - Distinguishing the cognitive processes of mindfulness: Developing a standardised
      mindfulness technique for use in longitudinal randomised control trials.
AB  - A capacity model of mindfulness is adopted to differentiate the cognitive faculty
      of mindfulness from the metacognitive processes required to cultivate this
      faculty in mindfulness training. The model provides an explanatory framework
      incorporating both the developmental progression from focussed attention to open
      monitoring styles of mindfulness practice, along with the development of
      equanimity and insight. A standardised technique for activating these processes
      without the addition of secondary components is then introduced. Mindfulness
      based interventions currently available for use in randomised control trials
      introduce components ancillary to the cognitive processes of mindfulness,
      limiting their ability to draw clear causative inferences. The standardised
      technique presented here does not introduce such ancillary factors, rendering it
      a valuable tool with which to investigate the processes activated in mindfulness
      practice.

PMID- 28499258
TI  - Trajectories of positive alcohol expectancies and drinking: An examination of
      young adults in the US and Sweden.
AB  - Positive alcohol expectancies and alcohol use tend to increase from adolescence
      to young adulthood, yet little is known about the associations between these
      constructs across cultures. The current study adds to the extant literature by
      examining the growth trajectories of positive alcohol expectancies and drinking
      behavior among United States (US) and Swedish participants during a critical
      period where significant change in these outcomes may be expected to occur. A
      total of 870 (US, N=362; Sweden, N=508) high school seniors completed baseline, 6
      month, and 12-month assessments of alcohol expectancies and drinking (i.e.,
      drinks per week). Changes in positive alcohol expectancies and drinking behavior
      were examined using a parallel process latent growth model. In both samples,
      higher baseline levels of positive alcohol expectancies were associated with a
      higher number of drinks consumed per week at baseline. In the US sample, lower
      baseline levels of positive alcohol expectancies were associated with a greater
      increase in positive alcohol expectancies at 12-month follow-up, and lower
      baseline levels of drinks per week were associated with a greater increase in
      drinks consumed per week at 12-month follow-up. In the Swedish sample, an
      increase in positive alcohol expectancies over time was associated with an
      increase in drinks consumed per week over the same period of time. Additional
      research is needed to examine when and for whom expectancy-based alcohol
      interventions are most efficacious.

PMID- 28499259
TI  - Systematic review of social media interventions for smoking cessation.
AB  - BACKGROUND: Popular social media could extend the reach of smoking cessation
      efforts. In this systematic review, our objectives were: 1) to determine whether
      social media interventions for smoking cessation are feasible, acceptable, and
      potentially effective; 2) to identify approaches for recruiting subjects; and 3)
      to examine the specific intervention design components and strategies employed to
      promote user engagement and retention. METHODS: We searched Scopus, Medline,
      EMBASE, Cochrane Central, PsychINFO, CINAHL, and Web of Science through July 2016
      and reference lists of relevant articles. Included studies described social media
      interventions for smoking cessation and must have reported outcomes related to
      feasibility, acceptability, usability, or smoking-related outcomes. RESULTS: We
      identified 7 studies (all were published since 2014) that enrolled 9755
      participants (median=136 [range 40 to 9042]). Studies mainly used Facebook (n=4)
      or Twitter (n=2), and emerged as feasible and acceptable. Five studies reported
      smoking-related outcomes such as greater abstinence, reduction in relapse, and an
      increase in quit attempts. Most studies (n=6) recruited participants using online
      or Facebook advertisements. Tailored content, targeted reminders, and moderated
      discussions were used to promote participant engagement. Three studies found that
      active participation through posting comments or liking content may be associated
      with improved outcomes. Retention ranged from 35% to 84% (median=70%) across the
      included studies. CONCLUSIONS: Our review highlights the feasibility,
      acceptability and preliminary effectiveness of social media interventions for
      smoking cessation. Future research should continue to explore approaches for
      promoting user engagement and retention, and whether sustained engagement
      translates to clinically meaningful smoking cessation outcomes.

PMID- 28499260
TI  - Metal toxicity affects predatory stream invertebrates less than other functional
      feeding groups.
AB  - Ecosystem effects of heavy metals need to be identified for a retrospective risk
      assessment, and potential impacts need to be predicted for a prospective risk
      assessment. In this study, we established a strong correlation between the toxic
      pressure of dissolved metals and invertebrate species. We compiled available data
      from a wide geographical range of Australian streams that were contaminated with
      heavy metals [mainly copper (Cu) and zinc (Zn)] and the corresponding
      invertebrate communities. Heavy metal toxicity is positively related to the
      proportion of predators within the invertebrate community, represented by the
      predatorratio, with an effect threshold range of 2.6 MUg/L - 26 MUg/L for Cu and
      62 MUg/L - 617 MUg/L for Zn. These effect concentrations are in the ranges of the
      concentrations identified in model ecosystems and other field investigations and
      are just above the existing guideline limits. Heavy metals also affects the taxa
      richness negatively. Other community measures, such as the evenness, number of
      EPT (Ephemeroptera, Plecoptera, and Trichoptera) taxa, SPEcies At Risk
      (SPEAR)pesticides or SPEARsalinity were relatively poorly correlated with heavy
      metal toxicity in the streams. Therefore, we suggest applying the predatorratio
      within the community as a starting point for an indicator of the dissolved metal
      toxicity, the SPEARmetals.

PMID- 28499261
TI  - Structural signatures of water-soluble organic aerosols in contrasting
      environments in South America and Western Europe.
AB  - This study describes and compares the key structural units present in water
      soluble organic carbon (WSOC) fraction of atmospheric aerosols collected in
      different South American (Colombia - Medellin and Bogota, Peru - Lima, Argentina 
      Buenos Aires, and Brazil - Rio de Janeiro, Sao Paulo, and Porto Velho, during
      moderate (MBB) and intense (IBB) biomass burning) and Western European (Portugal 
      Aveiro and Lisbon) locations. Proton nuclear magnetic resonance (1H NMR)
      spectroscopy was employed to assess the relative distribution of non-exchangeable
      proton functional groups in aerosol WSOC of diverse origin, for the first time to
      the authors' knowledge in South America. The relative contribution of the proton
      functional groups was in the order H-C > H-C-C= > H-C-O > Ar-H, except in Porto
      Velho during MBB, Medellin, Bogota, and Buenos Aires, for which the relative
      contribution of H-C-O was higher than that of H-C-C=. The 1H NMR source
      attribution confirmed differences in aging processes or regional sources between
      the two geographic regions, allowing the differentiation between urban combustion
      related aerosol and biological particles. The aerosol WSOC in Aveiro, Lisbon, and
      Rio de Janeiro during summer are more oxidized than those from the remaining
      locations, indicating the predominance of secondary organic aerosols. Fresh
      emissions, namely of smoke particles, becomes important during winter in Aveiro
      and Sao Paulo, and in Porto Velho during IBB. The biosphere is an important
      source altering the chemical composition of aerosol WSOC in South America
      locations. The source attribution in Medellin, Bogota, Buenos Aires, and Lima
      confirmed the mixed contributions of biological material, secondary formation, as
      well as urban and biomass burning emissions. Overall, the information and
      knowledge acquired in this study provide important diagnostic tools for future
      studies aiming at understanding the water-soluble organic aerosol problem, their
      sources and impact at a wider geographic scale.

PMID- 28499262
TI  - Fate and O-methylating detoxification of Tetrabromobisphenol A (TBBPA) in two
      earthworms (Metaphire guillelmi and Eisenia fetida).
AB  - Tetrabromobisphenol A (TBBPA) is the world's most widely used brominated flame
      retardant but there is growing concern about its fate and toxicity in terrestrial
      organisms. In this study, two ecologically different earthworms, Metaphire
      guillelmi and Eisenia fetida, were exposed to soil spiked with 14C-labeled TBBPA
      for 21 days. M. guillelmi accumulated more TBBPA than E. fetida, evidenced by a
      2.7-fold higher 14C-uptake rate and a 1.3-fold higher biota-soil accumulation
      factor. Considerable amounts of bound residues (up to 40% for M. guillelmi and
      18% for E. fetida) formed rapidly in the bodies of both earthworms. 14C
      accumulated mostly in the gut of M. guillemi and in the skin of E. fetida,
      suggesting that its uptake by M. guillelmi was mainly via gut processes whereas
      in E. fetida epidermal adsorption predominated. The TBBPA transformation
      potential was greater in M. guillelmi than in E. fetida, since only 5% vs. 34% of
      extractable 14C remained as the parent compound after 21 days of exposure.
      Besides polar metabolites, the major metabolites in both earthworms were TBBPA
      mono- and dimethyl ethers (O-methylation products of TBBPA). Acute toxicity
      assessments using filter paper and natural soil tests showed that the methylation
      metabolites were much less toxic than the parent TBBPA to both earthworms. It
      indicated that earthworms used O-methylation to detoxify TBBPA, and M. guillelmi
      exhibited the higher detoxification ability than E. fetida. These results imply
      that if only the free parent compound TBBPA is measured, not only bioaccumulation
      may be underestimated but also its difference between earthworm species may be
      misestimated. The species-dependent fate of TBBPA may provide a better indicator
      of the differing sensitivities of earthworms to this environmental contaminant.

PMID- 28499263
TI  - Effect of fumigation with chloropicrin on soil bacterial communities and genes
      encoding key enzymes involved in nitrogen cycling.
AB  - Chloropicrin (CP) is a potential alternative for methyl bromide as a soil
      fumigant given that the use of methyl bromide has become limited. However, little
      is known about how fumigation with CP affects the condition of the soil microbial
      community. In this study, 16S rRNA amplicon sequencing and quantitative PCR were
      combined to investigate the effect of CP on soil bacterial community. In total,
      938,922 effective reads were obtained from 18 samples and clustered into 58,662
      operational taxonomic units at a similarity cut-off of 97%. Both approaches
      showed that the primary structure of bacterial community in soil did not
      significantly change at the phylum level after fumigation, but CP had a
      significant impact on the abundance of the bacterial microbiome that was
      recovered and identified. Additionally, bacterial community diversity decreased
      significantly, and there was a shift in the predominant populations.
      Staphylococcus, Actinomadura, Acinetobacter and Streptomyces significantly
      decreased in number or disappeared, and Bacteroides, Lachnoclostridium,
      Pseudoalteromonas, Colwellia, Idiomarina and Cobetia became the new predominant
      populations. In addition, some species associated with biodegradation, such as
      Sphingomonas spp. and Rhodococcus spp., significantly increased in number. The
      abundance of ammonia-oxidizing archaea (AOA) were significantly inhibited, yet
      the abundance of ammonia-oxidizing bacteria (AOB) significantly increased, and
      denitrification was significantly promoted. These changes in bacterial flora can
      considerably impact soil function and health and lead to negative effects on the
      environment surrounding fumigated soils, indicating the need for proactive risk
      management. Our study provides useful information for environmental safety
      assessments of CP in China.

PMID- 28499265
TI  - Nanoagroparticles emerging trends and future prospect in modern agriculture
      system.
AB  - Increment of technical knowledge has remarkably uplifted logical thinking among
      scientific communities to shape the theoretical concepts into near product
      oriented research. The concept of nanotechnology has overwhelmed almost all forms
      of lives and has traded its applications in myriad fields. Despite rapid
      expansion of nanotechnology, sustainable competitions still do exist in the field
      of agriculture. In current scenario, agriculture is a manifestation demand to
      provide adequate nutrition for relentless growing global population. It is
      estimated that nearly one-third of the global crop production is destroyed
      annually. The loss owes to various stresses such as pest infestation, microbial
      pathogens, weeds, natural calamities, lack of soil fertility and much more. In
      order to overcome these limitations, various technological strategies are
      implemented but a majority of these have their own repercussions. Hence there is
      a scrawling progress on the evaluation of nanoparticles into agriculture sector
      which can reform the modern agricultural system. Applications of these
      nanomaterials can add tremendous value in the current scenario of a global food
      scarcity. Nanotechnology can address the adverse effects posed by the abundant
      use of chemical agrochemicals which are reported to cause biomagnification in an
      ecosystem. Based on these facts and consideration, present review envisages on
      nanoparticles as nanoherbicides, nanopesticides, onsite detection agro-pathogens
      and nanoparticles in post harvest management. The review also elucidates on the
      importance of nanoparticles in soil fertility, irrigation management and its
      influence on improving crop yield. With scanty reports available on
      nanotechnology in agriculture system, present review attributes toward developing
      nanoagroparticles as the future prospect which can give new facelift for existing
      agriculture system.

PMID- 28499264
TI  - Initial clonogenic potential of human endothelial progenitor cells is predictive
      of their further properties and establishes a functional hierarchy related to
      immaturity.
AB  - Endothelial progenitor cells (EPCs) generate in vitro Endothelial Colony Forming
      Cells (ECFCs) combining features of endothelial and stem/progenitor cells. Their
      angiogenic properties confer them a therapeutic potential for treating ischemic
      lesions. They may be isolated from umbilical cord blood (CB-ECFCs) or peripheral
      adult blood (AB-ECFCs). It is generally accepted that CB-ECFCs are more
      clonogenic, proliferative and angiogenic than AB-ECFCs. Nevertheless, only a few
      studies have focused on the functional heterogeneity of CB-ECFCs from different
      individuals. Moreover, AB-ECFC loss of function is yet to be precisely described.
      We have focused on these two issues that are critical for clinical perspectives.
      The detailed clonogenic profile of CB-ECFCs and AB-ECFCs was obtained and
      revealed a high inter individual heterogeneity and the absence of correlation
      with age. Most CB-ECFCs yielded initial colonies and had functional properties
      similar to those of AB-ECFCs. Conversely, a high clonogenicity was associated
      with an enhanced proliferative and angiogenic potential and stemness gene
      overexpression, confirming that immaturity, lost by AB-ECFCs, was a prerequisite
      to functionality. We thus demonstrated the importance of selecting CB-ECFCs
      according to specific criteria, and we propose using the initial clonogenicity as
      a relevant marker of their potential efficacy on vascular repair.

PMID- 28499266
TI  - Model-based optimization of parameters for degradation reaction of an
      organophosphorus pesticide, paraoxon, using CeO2 nanoparticles in water media.
AB  - Degradation and body surface decontamination is vital to prevent the skin
      penetration of paraoxon (POX), an organophosphorus pesticide, and victims
      poisoning. CeO2 demonstrated a good efficacy for the degradation of POX. The aim
      of the study was to develop a model which includes the impact of weight of CeO2,
      POX and diluent volumes on the degradation kinetics. The modelling was realized
      with rapid and simple experiments carried out in tubes, in aqueous diluent which
      contained ions in order to be in accordance with in vitro skin decontamination
      conditions. CeO2 had degraded from 5% (in case of 7.5mmol of POX per gram of
      CeO2) to 100% (0.002mmol of POX per gram of CeO2) of POX. Different kinetic
      models were tested. Using the particle aggregation kinetic model, the simulated
      and experimental data were in a good accordance. It highlighted the importance of
      particles aggregation due to salts and consistency of the mix on the degradation
      efficiency of CeO2. The model worked also really well to predict the degradation
      efficiency of CeO2 powders during in vitro skin experiments. However, it did not
      correctly forecast with an aqueous decontaminant, containing CeO2.

PMID- 28499267
TI  - A novel germline TP53 mutation p.Pro190Arg detected in a patient with lung and
      bilateral breast cancers.
AB  - PURPOSE: Li-Fraumeni syndrome (LFS) is a rare genetic disease with strong
      predispositions to multiple early-onset neoplasms, mostly sarcomas, breast
      cancers, brain tumors and adrenocortical carcinomas (LFS core cancers). In most
      LFS families the germline mutations of TP53 tumor suppressor gene were found.
      Lung cancer does not belong to the core cancers of LFS, however its higher
      incidence is observed in families with TP53 mutations. Our aim was to search for
      TP53 mutations in female lung cancer patients whose clinico-demographic
      characteristics suggested a probable genetic predisposition to the disease.
      MATERIALS AND METHODS: The coding region of TP53 from blood DNA was sequenced
      using Sanger method. The functioning of detected mutation was tested by
      luciferase reporter assay. RESULTS: We found a nucleotide substitution c.569C>G,
      p.Pro190Arg, which was not described in the TP53 germline mutation database
      (http://p53.iarc.fr/TP53GermlineMutations.aspx). The mutation destroys the
      ability of p53 to transactivate BAX promoter and significantly reduces
      transactivation potential of p53 toward the promoter of MDM2 gen. CONCLUSION: We
      identified novel germline mutation of TP53.

PMID- 28499268
TI  - First universal pharmacophore model for hERG1 K+ channel activators: acthER.
AB  - The intra-cavitary drug blockade of hERG1 channel has been extensively studied,
      both experimentally and theoretically. Structurally diverse ligands inadvertently
      block the hERG1 K+ channel currents lead to drug induced Long QT Syndrome (LQTS).
      Accordingly, designing either hERG1 channel openers or current activators, with
      the potential to target other binding pockets of the channel, has been introduced
      as a viable approach in modern anti-arrhythmia drug development. However, reports
      and investigations on the molecular mechanisms underlying activators binding to
      the hERG1 channel remain sparse and the overall molecular design principles are
      largely unknown. Most of the hERG1 activators were discovered during mandatory
      screening for hERG1 blockade. To fill this apparent deficit, the first universal
      pharmacophore model for hERG1 K+ channel activators was developed using PHASE. 3D
      structures of 18 hERG1 K+ channel activators and their corresponding measured
      binding affinity values were used in the development of pharmacophore models.
      These compounds spanned a range of structurally different chemotypes with
      moderate variation in binding affinity. A five sites AAHRR (A, hydrogen-bond
      accepting, H, hydrophobic, R, aromatic) pharmacophore model has shown reasonable
      high statistical results compared to the other developed more than 1000
      hypotheses. This model was used to construct steric and electrostatic contour
      maps. The predictive power of the model was tested with 3 external test set
      compounds as true unknowns. Finally, the pharmacophore model was combined with
      the previously developed receptor-based model of hERG1 K+ channel to develop and
      screen novel activators. The results are quite striking and it suggests a greater
      future role for pharmacophore modeling and virtual drug screening simulations in
      deciphering complex patterns of molecular mechanisms of hERG1 channel openers at
      the target sites. The developed model is available upon request and it may serve
      as basis for the synthesis of novel therapeutic hERG1 activators.

PMID- 28499269
TI  - Identification of novel serotonin reuptake inhibitors targeting central and
      allosteric binding sites: A virtual screening and molecular dynamics simulations
      study.
AB  - The serotonin (5-hydroxytryptamine, 5HT) transporter (SERT) is a member of
      neurotransmitter sodium symporter (NSS) family, which maintains neurotransmitter
      by reuptaking 5HT into synapses. Decrease in serotonin concentrations in synaptic
      clefts have been reported to cause psychological and neurological disorders.
      Therefore, inhibition of SERT is a potent strategy for the treatment of related
      diseases such as depression. In this study, approximately 260,000 small molecules
      from an available chemical database have been virtually screened both at central
      and allosteric binding sites of SERT to identify potent novel candidate SERT
      inhibitors. A set of docking algorithms were used to predict binding modes and
      energies of compounds. Screening analyses led three top-ranked hit compounds
      (160234, Otava ID: 7118020138; 159166, Otava ID: 7117171303; and 69419, Otava ID:
      118671819) for central binding site (S1) and one compound (93507, Otava ID:
      6248262) for allosteric binding site (S2). These promising compounds are then
      subjected to long multiple molecular dynamics (MD) simulations to elucidate their
      structural and dynamical profiles at the binding cavities of SERT. Higher
      predicted binding affinities of identified compounds were also confirmed with
      binding free energy calculations (MM/GBSA) in comparison with the reference
      central and allosteric binding site inhibitors, paroxetine (8PR) and escitalopram
      (68P), respectively. To the best of our knowledge, the present work is the first
      structure-based high throughput virtual screening study reported using recently
      revealed crystal structure of SERT for screening inhibitors from chemical
      databases on S1 and S2 binding sites. Small molecule library screening study
      yielded candidate compounds both at central and allosteric binding site of SERT,
      and further experimentation may pave the way for developing novel strong
      inhibitors.

PMID- 28499270
TI  - Simulation studies on structural and thermal properties of alkane thiol capped
      gold nanoparticles.
AB  - The structural and thermal properties of the passivated gold nanoparticles were
      explored employing molecular dynamics simulation for the different surface
      coverage densities of the self-assembled monolayer (SAM) of alkane thiol. The
      structural properties of the monolayer protected gold nanoparticles such us
      overall shape, organization and conformation of the capping alkane thiol chains
      were found to be influenced by the capping density. The structural order of the
      thiol capped gold nanoparticles enhances with the increase in the surface
      coverage density. The specific heat capacity of the alkane thiol capped gold
      nanoparticles was found to increase linearly with the thiol coverage density.
      This may be attributed to the enhancement in the lattice vibrational energy. The
      present simulation results suggest, that the structural and thermal properties of
      the alkane thiol capped gold nanoparticles may be modified by the suitable
      selection of the SAM coverage density.

PMID- 28499271
TI  - Atom and receptor based 3D QSAR models for generating new conformations from
      pyrazolopyrimidine as IL-2 inducible tyrosine kinase inhibitors.
AB  - In the current study, quantitative three-dimensional structure-activity
      relationship (3D-QSAR) method was performed to design a model for new chemical
      entities by utilizing pyrazolopyrimidines. Their inhibiting activity on receptor
      IL-2 Itk correlates descriptors based on topology and hydrophobicity. The best
      model developed by ligand-based (atom-based) approach has correlation-coefficient
      of r2: 0.987 and cross-validated squared correlation-coefficient of q2: 0.541
      with an external prediction capability of r2: 0.944. Whereas the best selected
      model developed by structured-based (receptor-based) approach has correlation
      coefficient of r2: 0.987, cross-validated squared correlation-coefficient of q2:
      0.637 with an external predictive ability of r2: 0.941. The statistical
      parameters prove that structure-based gave a better model to design new chemical
      scaffolds. The results achieved indicated that hydrophobicity at R1 location play
      a vital role in the inhibitory activity and introduction of appropriately bulky
      and strongly hydrophobic-groups at position 3 of the terminal phenyl-group which
      is highly significant to enhance the activity. Six new pyrazolopyrimidine
      derivatives were designed. Docking simulation study was carried out and their
      inhibitory activity was predicted by the best structure based model with
      predictive activity of ranging from 8.43 to 8.85 log unit. The interacting
      residues PHE435, ASP500, LYS391, GLU436, MET438, CYS442, ILE369, VAL377 of PDB
      4HCT were studied with respect to type of bonding with the new compounds. This
      study was aimed to search out more potent inhibitors of IL-2 Itk.

PMID- 28499272
TI  - Effects of cortisol on the memory bias for emotional words? A study in patients
      with depression and healthy participants using the Directed Forgetting task.
AB  - Mood congruent alterations in information processing such as an impaired memory
      bias for emotional information and impaired inhibitory functions are prominent
      features of a major depressive disorder (MDD). Furthermore, in MDD patients
      hypothalamic-pituitary-adrenal axis dysfunctions are frequently found. Impairing
      effects of stress or cortisol administration on memory retrieval as well as
      impairing stress effects on cognitive inhibition are well documented in healthy
      participants. In MDD patients, no effect of acute cortisol administration on
      memory retrieval was found. The current study investigated the effect of acute
      cortisol administration on memory bias in MDD patients (N = 55) and healthy
      controls (N = 63) using the Directed Forgetting (DF) task with positive, negative
      and neutral words in a placebo controlled, double blind design. After oral
      administration of 10 mg hydrocortisone/placebo, the item method of the DF task
      was conducted. Memory performance was tested with a free recall test. Cortisol
      was not found to have an effect on the results of the DF task. Interestingly,
      there was significant impact of valence: both groups showed the highest DF score
      for positive words and remembered significantly more positive words that were
      supposed to be remembered and significantly more negative words that were
      supposed to be forgotten. In general, healthy participants remembered more words
      than the depressed patients. Still, the depressed patients were able to inhibit
      intentionally irrelevant information at a comparable level as the healthy
      controls. These results demonstrate the importance to distinguish in experimental
      designs between different cognitive domains such as inhibition and memory in our
      study.

PMID- 28499273
TI  - Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse
      Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease
      development.
AB  - NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the
      progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty
      liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that
      palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1beta
      (IL-1beta) secretion in Kupffer cells (KCs). However, the specific mechanism of
      the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms
      by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3
      on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine
      choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/-
      (thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs. We found
      that the expressions of NLRP3 and TXNIP in human liver tissues were higher in
      NASH group than in NAFL group. Furthermore, co-immunoprecipitation analyses show
      that activation of the TXNIP-NLRP3 inflammasome protein complex occurred in KCs
      of NASH WT mice rather than NAFL WT mice, thus suggesting that the formation and
      activation of this protein complex is mainly involved in the development of NASH.
      NLRP3-/- mice exhibited less severe NASH than WT mice in MCD diet model, whereas
      TXNIP deficiency enhanced NLRP3 inflammasome activation and exacerbated liver
      injury. PA triggered the activation and co-localization of the NLRP3 inflammasome
      protein complex in KCs isolated from WT and TXNIP-/- but not NLRP3-/- mice, and
      most of the complex co-localized with mitochondria of KCs following PA
      stimulation. Taken together, our novel findings indicate that TXNIP plays a
      protective and anti-inflammatory role in the development of NAFLD through binding
      and suppressing NLRP3.

PMID- 28499280
TI  - Help and Care Seeking for Sexually Transmitted Infections Among Youth in Low- and
      Middle-Income Countries.
AB  - BACKGROUND: The ability to seek help or medical care for sexually transmitted
      infections (STIs) is vital for sexually active youth; yet, their needs are often
      unmet. METHODS: We conducted a qualitative systematic review of studies to assess
      youth and provider views about the behaviors of young people in help seeking and
      care seeking for STI services in low- and middle-income countries. We searched
      peer-reviewed literature for studies published between 2001 and 2014 with a study
      population of youth (age, 10-24 years) and/or health service providers. Eighteen
      studies were identified for inclusion from 18 countries. Thematic analyses
      identified key themes across the studies. RESULTS: The majority of studies
      included discussion of youth not seeking treatment, resorting to self-treatment,
      or waiting to access care, suggesting that many youth still do not seek timely
      care for STIs. Youth desired more information on sexual health and cited barriers
      related to fear or taboos in obtaining help or information, especially from
      providers or parents. Many did not recognize symptoms or waited until symptoms
      worsened. However, many youth were able to identify a number of sources for STI
      related care including public and private clinics, pharmacies, alternative
      healers, and nongovernmental organizations. Youth's help seeking and care seeking
      preferences were frequently influenced by desires for confidentiality,
      friendliness, and cost. CONCLUSIONS: Youth in low- and middle-income countries
      experience significant barriers in help seeking for STIs and often do not seek or
      postpone medical care. Improving uptake may require efforts to address clinic
      systems, provider attitudes, confidentiality, and cultural norms related to youth
      sexuality.

PMID- 28499281
TI  - Assortativity and Mixing by Sexual Behaviors and Sociodemographic Characteristics
      in Young Adult Heterosexual Dating Partnerships.
AB  - BACKGROUND: Assortative sexual mixing, the tendency for individuals to choose
      partners with similar characteristics to themselves, may be an important
      contributor to the unequal distribution of sexually transmitted infections in
      populations. We analyzed the tendency for assortative mixing on demographic and
      sexual behaviors characteristics in newly formed young adults dating
      partnerships. METHODS: Women aged 18 to 24 years and their male sexual partners
      of no more than 6 months were recruited during 2005 to 2010 at universities in
      Montreal, Canada. New dating partners were also prospectively recruited during
      the 2-year follow-up. We used Spearman and Newman coefficients to examine
      correlations between partners' demographic characteristics and sexual behaviors,
      and multivariable logistic modeling to determine which characteristics were
      assortative. RESULTS: Participants in 502 recruited partnerships were assortative
      on age (Spearman P = 0.60), smoking behavior (P = 0.43), ethnicity (Newman
      coefficient=0.39), lifetime number of sexual partners (P = 0.36), sex partner
      acquisition rates (P = 0.22), gap length between partnerships (P = 0.20), and on
      whether they had concurrent partners (P = 0.33). Partners were assortative on
      number of lifetime partners, sexual partner acquisition rates, concurrency, and
      gap length between partnerships even after adjustment for demographic
      characteristics. Reported condom use was correlated between initial and
      subsequently recruited partners (P = 0.35). There was little correlation between
      the frequencies of vaginal/oral/digital/anal sex between subsequent partnerships.
      CONCLUSIONS: Dating partnerships were substantially assortative on various sexual
      behaviors as well as demographic characteristics. Though not a representative
      population sample, our recruitment of relatively new partnerships reduces
      survivor bias inherent to cross-sectional surveys where stable long-term
      partnerships are more likely to be sampled.

PMID- 28499282
TI  - Can Social Network Analysis Help Address the High Rates of Bacterial Sexually
      Transmitted Infections in Saskatchewan?
AB  - BACKGROUND: Saskatchewan has one of the highest rates of gonorrhea among the
      Canadian provinces-more than double the national rate. In light of these high
      rates, and the growing threat of untreatable infections, improved understanding
      of gonorrhea transmission dynamics in the province and evaluation of the current
      system and tools for disease control are important. METHODS: We extracted data
      from a cross-sectional sample of laboratory-confirmed gonorrhea cases between
      2003 and 2012 from the notifiable disease files of the Regina Qu'Appelle Health
      Region. The database was stratified by calendar year, and social network analysis
      combined with statistical modeling was used to identify associations between
      measures of connection within the network and the odds of repeat gonorrhea and
      risk of coinfection with chlamydia at the time of diagnosis. RESULTS: Networks
      were highly fragmented. Younger age and component size were positively associated
      with being coinfected with chlamydia. Being coinfected, reporting sex trade
      involvement, and component size were all positively associated with repeat
      infection. CONCLUSIONS: This is the first study to apply social network analysis
      to gonorrhea transmission in Saskatchewan and contributes important information
      about the relationship of network connections to gonorrhea/chlamydia coinfection
      and repeat gonorrhea. This study also suggests several areas for change of
      systems-related factors that could greatly increase understanding of social
      networks and enhance the potential for bacterial sexually transmitted infection
      control in Saskatchewan.

PMID- 28499283
TI  - Chlamydia trachomatis Incidence Using Self-Reports and Serology by Gender, Age
      Period, and Sexual Behavior in a Birth Cohort.
AB  - BACKGROUND: Although understanding chlamydia incidence assists prevention and
      control, analyses based on diagnosed infections may distort the findings.
      Therefore, we determined incidence and examined risks in a birth cohort based on
      self-reports and serology. METHODS: Self-reported chlamydia and behavior data
      were collected from a cohort born in New Zealand in 1972/3 on several occasions
      to age 38 years. Sera drawn at ages 26, 32, and 38 years were tested for
      antibodies to Chlamydia trachomatis Pgp3 antigen using a recently developed
      assay, more sensitive in women (82.9%) than men (54.4%). Chlamydia incidence by
      age period (first coitus to age 26, 26-32, and 32-38 years) was calculated
      combining self-reports and serostatus and risk factors investigated by Poisson
      regression. RESULTS: By age 38 years, 32.7% of women and 20.9% of men had
      seroconverted or self-reported a diagnosis. The highest incidence rate was to age
      26, 32.7 and 18.4 years per 1000 person-years for women and men, respectively.
      Incidence rates increased substantially with increasing number of sexual
      partners. After adjusting age period incidence rates for partner numbers, a
      relationship with age was not detected until 32 to 38 years, and then only for
      women. CONCLUSIONS: Chlamydia was common in this cohort by age 38, despite the
      moderate incidence rates by age period. The strongest risk factor for incident
      infection was the number of sexual partners. Age, up to 32 years, was not an
      independent factor after accounting for partner numbers, and then only for women.
      Behavior is more important than age when considering prevention strategies.

PMID- 28499284
TI  - Emergence and Spread of Neisseria gonorrhoeae Isolates With Decreased
      Susceptibility to Extended-Spectrum Cephalosporins in Argentina, 2009 to 2013.
AB  - BACKGROUND: The emergence of Neisseria gonorrhoeae strains with decreased
      susceptibility to cephalosporins represents a major concern globally. The aim of
      this study was to examine the phenotypic and molecular characteristics of N.
      gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime in
      Argentina. METHODS: A total of 1987 isolates were collected during 2009 and 2013.
      The susceptibility to penicillin G, tetracycline, ciprofloxacin, cefixime,
      ceftriaxone, and azithromycin was determined using the agar dilution method. The
      major extended-spectrum cephalosporin resistance determinants (penA, mtrR, and
      porB1b) were sequenced in 42 N. gonorrhoeae isolates that showed decreased
      susceptibility to ceftriaxone (minimum inhibitory concentration [MIC], 0.06-0.125
      mg/L) and cefixime (MIC, 0.125-0.25 mg/L). Genotyping by N. gonorrhoeae
      multiantigen sequence typing (NG-MAST) was performed. RESULTS: Between 2009 and
      2013, there was a shift in the modal MICs for ceftriaxone. Among the 42 isolates
      exhibiting decreased susceptibility to ceftriaxone and cefixime, 95.2% were
      resistant to penicillin G, 95.2% to tetracycline, 97.6% to ciprofloxacin, and
      33.3% to azithromycin. Thirty-five (83.3%) of the 42 isolates had a mosaic penA
      allele XXXIV, which has been previously associated with resistance to ceftriaxone
      and cefixime as well as treatment failures. The isolates that contained the
      mosaic penicillin-binding protein 2 (PBP2) XXXIV were associated with NG-MAST
      ST1407 or closely related genotypes. CONCLUSIONS: In Argentina, N. gonorrhoeae
      isolates with decreased susceptibility to cefixime and ceftriaxone have now
      emerged, mostly due to the introduction of the internationally spread multidrug
      resistant NG-MAST ST1407.

PMID- 28499285
TI  - Keeping an Eye on Chlamydia and Gonorrhea Conjunctivitis in Infants in the United
      States, 2010-2015.
AB  - Perinatal transmission of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae
      (GC) can result in conjunctivitis in infants. We examined national rates of
      reported CT/GC conjunctivitis among infants. Surveillance of these infections is
      heavily affected by the completeness of reported data on specimen source and age.
      Alternative data sources should be evaluated.

PMID- 28499287
TI  - Impact of Eligibility Criteria on Participant Enrollment for a Randomized
      Clinical Trial of Gonorrhea Treatment.
AB  - BACKGROUND: High rates of failure to qualify for clinical trial participation
      increase time and cost required for study completion. Identification of
      remediable reasons for prescreen failure can help reduce prescreen failure rates
      and improve study cost effectiveness. METHODS: Reasons for prescreen failure to
      qualify for participation in a phase 2 randomized clinical trial of treatment of
      uncomplicated urogenital gonorrhea were collected from prescreening logs. Reasons
      were categorized based on whether the reason was that the subject failed to meet
      eligibility criteria or declined participation. Subjects who failed prescreening
      but could have been enrolled under protocol amendments were used to estimate
      potential cost savings had enrollment completed sooner. RESULTS: Over 88%
      (1373/1554) of potential study candidates were not enrolled. The majority (68.8%)
      of nonenrolled subjects failed prescreening due to not meeting eligibility
      criteria, whereas 31.0% declined to participate. The most common reasons for
      failure to qualify were having only nonurogenital gonorrhea (16.4%), limited time
      (13.1%), and being on antiretroviral therapy (7.5%). Potential cost savings if
      protocol amendments affecting eligibility had been instituted earlier were
      estimated at US $127,500. CONCLUSIONS: Careful attention to reasons for prescreen
      failure can inform clinical trial protocol development to address trial design
      features that may impact successful enrollment. More efficient subject enrollment
      can result in substantial cost savings.

PMID- 28499286
TI  - Retrospective Review of Gonococcal and Chlamydial Cases of Epididymitis at 2
      Canadian Sexually Transmitted Infection Clinics, 2004-2014.
AB  - Fifty-seven cases of gonococcal and chlamydial infections complicated by acute
      epididymitis seen at 2 Alberta STI clinics from 2004 to 2014 were reviewed. The
      majority responded to treatment recommended by national guidelines. Three of 6
      treatment failures were not treated according to guidelines.

PMID- 28499288
TI  - Impact of Number of Human Papillomavirus Vaccine Doses on Genital Warts Diagnoses
      Among a National Cohort of U.S. Adolescents.
AB  - BACKGROUND: The impact of fewer than 3 doses of human papillomavirus (HPV)
      vaccine on genital warts is uncertain. METHODS: Using the Truven Health Analytics
      Marketscan administrative database, we compared rates of genital warts among
      women receiving 0, 1, 2, or 3 doses of HPV vaccine. Females aged 9 to 18 years on
      January 1, 2007, who were continuously enrolled in the database through December
      31, 2013, were included. Patients were assigned an HPV dose state (0, 1, 2, or 3)
      based on the last recorded dose. The exposure period began on January 1, 2007, or
      the date of the final HPV dose, and lasted until the first diagnosis of genital
      warts or December 31, 2013. Multivariable Poisson regression was performed to
      determine the risk of genital warts associated with vaccine doses. RESULTS: Among
      387,906 subjects, mean age and exposure period were 14.73 and 5.64 years,
      respectively. The proportions of doses received were: 52.1%, 7.8%, 9.4%, and
      30.7% for 0, 1, 2, and 3 doses, respectively. The rate of genital warts was
      1.97/1000 person-years. Receipt of 0 or 1 dose was associated with more genital
      warts than 3 doses. The effectiveness of 2 doses following current Centers for
      Disease Control and Prevention guidelines was similar to 3 doses. The risk of
      genital warts rose with age. CONCLUSIONS: Prevention of genital warts is higher
      with completion of 3 vaccine doses than with 1 dose, though 2-dose
      recommendations appear to provide similar protection. Prospective effectiveness
      studies of recommended 2-dose schedules against clinical endpoints including
      persistent infection, genital warts, and cervical dysplasia are necessary to
      ensure long-term protection of vaccinated cohorts.

PMID- 28499290
TI  - Molecular Typing of Syphilis-Causing Strains Among Human Immunodeficiency Virus
      Positive Patients in Antwerp, Belgium.
AB  - Centers for Disease Control and Prevention and sequencing-based treponeme typing
      was used to analyze 72 blood samples, collected from human immunodeficiency virus
      and syphilis co-infected patients during 2014 to 2015 in Antwerp, Belgium. Twenty
      nine (40.3%) isolates were polymerase chain reaction positive for Treponema
      pallidum, and all tested were macrolide-resistant. Four genotypes were identified
      by sequencing-based typing including two new genotypes, U4NR8 and SU9R8, whereas
      enhanced Centers for Disease Control and Prevention typing revealed 7 subtypes.

PMID- 28499289
TI  - Maternal Syphilis: An Independent Risk Factor for Mother to Infant Human
      Immunodeficiency Virus Transmission.
AB  - Syphilis is associated with increased human immunodeficiency virus acquisition
      and sexual transmission; we examined impact on human immunodeficiency virus
      mother-to-child transmission among mother-infant pairs enrolled in the India Six
      Week Extended-Dose Nevirapine study. Maternal syphilis, diagnosed serologically
      using Venereal Disease Research Laboratory titer plus Treponema Pallidum
      Hemagglutination Assay, was associated with 2.5-fold greater risk.

PMID- 28499292
TI  - ?

PMID- 28499291
TI  - A Survey of 25 North Carolina Health Departments/Districts on Knowledge,
      Attitudes, and Current Practices to Seeking Reimbursement From Third-Party Payers
      for Sexually Transmitted Disease Services.
AB  - BACKGROUND: North Carolina Administrative Code 10A Chapter 41A.0204 (a) states
      "local health departments shall provide diagnosis, testing, treatment, follow-up,
      and preventive services for syphilis, gonorrhea, chlamydia, ... These services
      shall be provided upon request and at no charge to the patient." Although health
      departments/districts may bill governmental or nongovernmental insurance
      providers for sexually transmitted disease (STD) services, current billing
      practices are unknown. Because of its high STD morbidity, the eastern region of
      North Carolina was targeted. METHODS: Using a Qualtrics Survey developed to
      measure attitudes as well as knowledge and reimbursement practices, this
      descriptive study was performed with staff from 25 eastern North Carolina health
      departments/districts. Snowball sampling was used to allow for greater inclusion.
      Analysis of data was performed at the individual and agency level based on types
      of questions in the survey. RESULTS: For knowledge, 87% of the respondents
      reported being aware of the possibility of reimbursement from third-party
      payers/commercial insurance carriers for STD services. In regard to current
      billing of these services, 20 health departments/districts (80%) reported they
      were billing these payers. When asked about their attitude of seeking
      reimbursement from commercial insurance, 92% reported it was acceptable or very
      acceptable. But when asked if STD services should remain a free service at the
      health department, 55% supported and 45% did not. CONCLUSIONS: These data provide
      a knowledge base for assisting health departments/districts to move forward in
      improving STD services as well as maximizing reimbursement from third-party
      payers/commercial insurance carriers when possible.

PMID- 28499293
TI  - [Current Audiological Diagnostics].
AB  - Today's audiological functional diagnostics is based on a stock of hearing tests,
      whose large number takes account of the variety of malfunctions of a complex
      sensory organ system and the necessity to examine it in a differentiated manner
      and at any age of life. The objective is to identify nature and origin of the
      hearing loss and to quantify its extent as far as necessary to dispose of the
      information needed to initiate the adequate medical (conservative or operational)
      treatment or the provision with technical hearing aids or prostheses. Moreover,
      audiometry provides the basis for the assessment of impairment and handicap and
      for the calculation of the degree of disability. In the present overview, the
      current state of the method inventory available for practical use is described,
      starting from basic diagnostics over to complex special techniques. The
      presentation is systematically grouped in subjective procedures, based on
      psychoacoustic exploration, and objective methods, based on physical
      measurements: preliminary hearing tests, pure tone threshold, suprathreshold
      processing of sound intensity, directional hearing, speech understanding in quiet
      and in noise, dichotic hearing, tympanogram, acoustic reflex, otoacoustic
      emissions and auditory evoked potentials. Apart from a few still existing gaps,
      this method inventory covers the whole spectrum of all clinically relevant
      functional deficits of the auditory system.

PMID- 28499294
TI  - ?
AB  - Hearing loss can be caused by a number of different pathological conditions. Some
      of them can be successfully treated, mainly by surgery, depending on the
      individual's disease process. However, the treatment of chronic sensorineural
      hearing loss with damaged cochlear structures usually needs hearing
      rehabilitation by means of technical amplification. During the last 2 decades
      tremendous improvements in hearing aid technology led to a higher quality in the
      hearing rehabilitation process. For example, due to sophisticated signal
      processing the acoustic feedback path could be reduced and hence open fitting
      options are available for even more subjects. In particular for high-frequency
      hearing loss the use of open fitting is an option. Both the users' acceptance and
      the perceived sound quality were significantly increased by open
      fittings.However, we are still faced with a low level of readiness in many
      hearing impaired subjects to accept acoustic amplification. Since ENT specialists
      play a key-role in hearing aid provision, they should promote early hearing aid
      rehabilitation and include this in the counselling even in subjects with mild and
      moderate hearing loss. Recent investigations demonstrated the benefit of early
      hearing aid use in this group of patients since this may help to reduce
      subsequent damages as auditory deprivation, social isolation, development of
      dementia, and cognitive decline. For subjects with tinnitus, hearing aids may
      also support masking by environmental sounds and enhance cortical inhibition.The
      present paper describes the latest development of hearing aid technology and the
      current state of the art for amplification modalities. Implications for both
      hearing aid indication and provision are discussed.

PMID- 28499295
TI  - [Tympanoplasty - News And New Perspectives].
AB  - Techniques and biomaterials for reconstructive middle ear surgery are under
      steady, ongoing development. At the same time, clinical post-surgery results are
      evaluated to determine success or failure of the therapy. Routine quality
      assessment and assurance is of growing importance in the medical field, and
      therefore also in middle ear surgery. The exact definition and acquisition of
      outcome parameters is essential for both a comprehensive and detailed quality
      assurance. These parameters are not the audiological results alone, but also
      additional individual parameters which influence the postoperative outcome after
      tympanoplasty. Selection of patients and the preoperative clinical situation, the
      extent of the ossicular chain destruction, the chosen reconstruction technique
      and material, the audiometric frequency selection and the observational interval
      are only some of them. If these parameters are not well documented comparative
      analyses between different studies are of limited value. The present overview
      aims to describe, compare and evaluate some of the existing assessment and
      scoring systems for middle ear surgery. Additionally, new methods for an
      intraoperative quality assessment in ossiculoplasty and the postoperative
      evaluation of suboptimal hearing results with imaging techniques are available.
      In the area of implant development functional elements were integrated in
      prostheses to enable not only good sound transmission but also compensation of
      occurring atmospheric pressure changes. In combination with other components for
      ossicular repair they can be used in a modular manner which, so far show
      experimentally and clinically promising results.

PMID- 28499296
TI  - [Implantable Hearing Devices].
AB  - Combined hearing loss is an essential indication for implantable hearing systems.
      Depending on the bone conduction threshold, various options are available:
      Patients with mild sensorineural deafness usually benefit from transcutaneous
      BCI, while percutaneous BCI systems are recommended also for moderate hearing
      loss. For combined hearing loss with moderate and high-grade cochlear hearing
      loss, active middle ear implants are recommended. For patients with
      incompatibilities or middle ear surgery, implants are a valuable and proven
      addition to the therapeutic options.

PMID- 28499297
TI  - [Diagnostics and Therapy of Idiopathic Sudden Sensorineural Hearing Loss].
AB  - This article reviews recent aspects of diagnostics, differential diagnostics and
      evidence in systemic and local therapy of idiopathic, sudden, sensorineural
      hearing loss (ISSHL). Since a number of disorders can be accompanied by sudden
      hearing loss a meaningful and targeted diagnostic strategy is of utmost
      importance. An important differential diagnosis of sudden hearing loss are
      intralabyrinthine schwannomas (ILS). The incidence of ILS is probably
      significantly underestimated. This may be due to the lack of awareness or lack of
      explicit search for an intralabyrinthine tumor on MRI or an inappropriate MRI
      technique ('head-MRI' instead of 'temporal bone-MRI' with too high slice
      thickness) for the evaluation of sudden hearing loss. Therefore, the request to
      the radiologist should specifically include the question for (or exclusion of) an
      ILS. With special MRI techniques, it is today possible to visualize an
      endolymphatic hydrops. The evidence in the therapy of ISSHL is - with respect to
      quality not quantity of studies - unsatisfying. The value of systemically (low
      dose) or intratympanically applied corticosteroids in the primary treatment of
      ISSHL is still unclear. In order to investigate the efficacy and safety of high
      dose corticosteroids in primary treatment for ISSHL a national, multicenter,
      three-armed, randomized, triple-blind controlled clinical trial is currently
      performed in Germany (http://hodokort-studie.hno.org/). After insufficient
      recovery of threshold with systemic therapy of ISSHL, intratympanic
      corticosteroid therapy appears to be associated with a significantly higher
      chance of improvement of hearing threshold than no therapy or placebo. Both,
      hearing gain and final hearing thresholds, however, appear to be independent of
      the start of secondary therapy. Based on the currently available data from
      clinical studies, no recommendation can be made with respect to type of
      corticosteroid and specifics of the intratympanic application protocol.

PMID- 28499298
TI  - [Cochlear Implant - State of the Art].
AB  - Cochlear implants are the treatment of choice for the auditory rehabilitation of
      patients with sensory deafness. They restore the missing function of inner hair
      cells by transforming the acoustic signal into electrical stimuli for activation
      of auditory nerve fibers. Due to the very fast technology development cochlear
      implants provide open-set speech understanding in the majority of patients
      including the use of the telephone. Children can achieve a near to normal speech
      and language development provided their deafness is detected early after onset
      and implantation is performed quickly thereafter. The diagnostic procedure as
      well as the surgical techniques have been standardized and can be adapted to the
      individual anatomical and physiological needs both in children and adults.
      Special cases such as cochlear obliteration or malformations can be addressed.
      Device failures and medical complications might require special measures and
      reimplantation which can be done in most cases in a straight forward way.
      Technology upgrades count for better performance.Future developments will focus
      on better electrode nerve interfaces by improving electrode technology. An
      increased number of electrical contacts as well as the biological treatment with
      regeneration of the dendrides growing onto the electrode will increase the number
      of electrical channels. This will give room for improved speech coding strategies
      in order to create the bionic ear, i. e. to restore the process of natural
      hearing by means of technology. The robot assisted surgery will allow for high
      precision surgery and reliable hearing preservation. Biological therapies will
      support the bionic ear. Methods are biohybrid electrodes which are coded by stem
      cells transplanted into the inner ear to enhance autoproduction of neurotrophins.
      Local drug delivery will focus on suppression of trauma reaction and local
      regeneration. Gene therapy by nanoparticles will hopefully lead to the
      preservation of residual hearing in patients being affected by genetic hearing
      loss. Overall the cochlear implant is a very powerful tool to rehabilitate
      patients with sensory deafness. More than 1 million of candidates in Germany
      today could benefit from this high technology auditory implant. Only 50,000 are
      implanted so far. In the future the procedure can be done under local anesthesia,
      will be minimal invasive and straight forward. Hearing preservation will be
      routine.

PMID- 28499299
TI  - [Current Diagnostic Procedures for Diagnosing Vertigo and Dizziness].
AB  - Modern diagnostic methods such as video head impulse test and cervical and ocular
      vestibular evoked myogenic potentials allow to measure canal and otolith function
      quantitatively and objectively. These methods contribute to a complex assessment
      of the functional integrity of all 5 sensory elements of the vestibular organ for
      the first time. Moreover, in combination with additional vestibular tests
      frequency specific and time depended changes of impairments of vestibular sensors
      and their pathways can be assessed. Over the past few years, new test methods
      have been established step by step in daily clinical diagnostic of vertigo and
      dizziness in acute vestibular syndrome and chronic complaints. Modern tests and
      concepts caused a paradigm shift in vestibular diagnostic. New classifications of
      vestibular disorders and algorithms provide a high diagnostic certainity and
      reliability although evidence-based investigations of diagnostic procedures are
      still missing.

PMID- 28499300
TI  - [Recent surgical options for vestibular vertigo].
AB  - Vertigo is not a well defined symptom but a heterogenous entity diagnosed and
      treated mainly by otolaryngologists, neurologists, internal medicine and primary
      care physicians. Most vertigo syndroms have a good prognosis and management is
      predominantly conservative, whereas the need for surgical therapy is rare, but
      for a subset of patients often the only remaining option. In this paper, we
      describe the development of surgical therapy for hydropic inner ear diseases,
      Meniere disease, dehiscence syndroms, perilymphatic fistulas, and benign
      paroxysmal vertigo. At the end, we shortly introduce the most recent development
      of vestibular implants. Surgical vestibular therapy is still indicated for
      selected patients nowadays when conservative options did not reduce symptoms and
      patients are still suffering. Success depends on the correct diagnosis and
      indication for the different procedures going along with an adequate patient
      selection. In regard to the invasiveness and the possible risks due to the
      surgery, in depth individual counselling is necessary. Ablative and destructive
      surgical procedures usually achieve a successful vertigo control, but go along
      with a high risk for hearing loss. Therefore, residual hearing has to be included
      in the decission making process for a surgical therapy.

PMID- 28499301
TI  - [Validation of the German Version of Tinnitus Functional Index (TFI)].
AB  - Tinnitus belongs to seriously debilitating auditory conditions and is often
      complicated by comorbidities such as insomnia, difficulties with concentration,
      depression, frustration and irritability. To facilitate the grading of symptoms
      and the effects of therapeutic strategies, we validated a German-version Tinnitus
      Functional Index (TFI) in 229 subjects suffering from chronic tinnitus. Outcome
      validity was assessed using the Tinnitus Questionnaire (TQ, German adaptation by
      Goebel u. Hiller [1998]). Construct validity was assessed using the "Hamburger
      Allgemeine Depressionsskala" (HADS). The German TFI featured excellent internal
      consistency (total score Cronbach's alpha=0.93). Factor analysis disclosed eight
      TFI subscales as proposed earlier by Meikle et al. [2012]. Intercorrelations were
      strong both between the TFI and the TQ (r=0.83), and between the TFI and the HADS
      (depression r=0.49, anxiety r=0.51). The German-version TFI qualifies as a rapid
      and statistically robust tool for grading the impact of tinnitus on daily living
      and for the measurements of therapeutic effects. Regarding depressive
      symptomatology, sensitivity of the TFI was comparable to that of the TQ.

PMID- 28499302
TI  - [Virtual Planning of Prosthetic Treatment of the Orbit].
AB  - Optimal positioning of bone-anchored implants in the treatment of patients with
      orbital prosthesis is challenging. The definition of implant axis as well as the
      positioning of the implants is important to prevent failures in prosthetic
      rehabilitation in these patients. We performed virtual planning of enossal
      implants at a base of a standard fan beam CT scan using the software
      CoDiagnostiXTM (DentalWings, Montreal, Canada). By 3D-printing a surgical guide
      for drilling and implant insertion was manufactured (Med-610TM, Stratasys,
      Rehovot, Israel). An orbital exenteration was performed in a patient after
      shrinkage of the eyelids 20 years after enucleation and radiation of the orbit
      due to rhabdomyosarcoma. 4 Vistafix-3 implants (CochlearTM, Cochlea, Centennial,
      USA) were primarily inserted after resection with the help of the 3D-surgical
      guide. Prosthetic rehabilitation could be achieved as preplanned to a predictable
      result. The individual prosthesis of the orbit showed good functional and
      esthetic outcome. The virtual 3D-planning of endosseous implants for prosthetic
      orbital and periorbital reconstruction is easy to use and facilitates optimal
      placement of implants especially in posttherapeutically altered anatomic
      situations.

PMID- 28499303
TI  - [Long-term Follow up and patient satisfaction after tympanoplasty with Titanium
      Clip-Prothesis].
AB  - Aim of the present study is to evaluate the long term results of ossiculoplasty
      using titanium clip prosthesis. A retrospective analysis with prospective follow
      up has been done including for all patients who had a Clip-PORP implanted between
      the years 2002-2013. Following this, audiometric hearing results were measured
      with clinical examination including otoscopy and quality of life evaluation using
      Glasgow benefit inventory. 48 patients (51 ears, 29 men, 19 women, average age
      44.1 years) received followed up after an average duration of 6.3 years. The
      overall air-bone-gap (0.5-4 kHz) decreased from 22.8 dB preoperatively to 14.6 dB
      postoperatively (p<=0.001). The most frequent indication for surgical treatment
      were cholesteatomas and recurrent cholesteatomas (52%), chronic inflammation of
      middle ear (12%), revision of radical mastoidectomy (8%) and disturbance in sound
      conduction after previous operation (14%). Tympanic membrane was closed in 47
      times (92,2%), 4 times (7,8%) there was a defect. Clip-PORP was in situ 39 times
      (75%), protrusion and disposal were detected 6 times (11,8%) and 2 times (4%),
      respectively. However, 1 time (2%) the prothesis was lost or evaluation was not
      possible (3 times, 5,9%). The overall patient satisfaction and general subscale
      score after the treatment was beneficially evaluated. There was no change in
      social support score nore the physical health score. In summary, the ossicular
      chain reconstruction using titan Clip-PORP is safe and well established. Also in
      long-term analysis stable hearing results due to reduction of air bone gap are
      represented. The subjective quality of life is sustainable improved.

PMID- 28499304
TI  - Isolation and Structure Characterization of Cytotoxic Phorbol Esters from the
      Seeds of Croton tiglium.
AB  - Nine new and eleven known phorbol esters were isolated from an acetone extract of
      the seeds of Croton tiglium. Their structures were determined by extensive
      analysis of spectroscopic data. Eleven of these compounds were evaluated for
      their inhibition activity on human tumor cell lines HL-60 and lung carcinoma
      A549. 12-O-Tiglylphorbol-13-acetate (11), 12-O-(2-methyl)-butyrylphorbol-13
      aetate (12), and 12-O-tiglylphorbol-13-isobutyrate (13) exhibited strong
      inhibition activity against both HL-60 and A549 cell lines with IC50 values <=
      0.02 and <= 0.1 ug/mL, respectively. Compound 18 showed strong inhibition
      activity against the HL-60 cell line with an IC50 value of 0.02 ug/mL.

PMID- 28499305
TI  - Aristolic Acid Derivatives from the Bark of Antidesma ghaesembilla.
AB  - Antidesma ghaesembilla is an important medicinal and food plant in many Asian
      countries. Ten substances could be isolated from the dichloromethane and methanol
      extract: sitostenone (3), daucosterol (4), chavibetol (5), asperphenamate (6),
      protocatechuic acid (7), vanillic acid-4-O-beta-D-glucoside (8), 1-O-beta-D
      glucopyranosyl-3-O-methyl-phloroglucinol (9), and aristolic acid II-8-O-beta-D
      glucoside (10), and two new aristolic acid derivatives, 10-amino-5,7-dimethoxy
      aristolic acid II (= 6-amino-9,11-dimethoxyphenanthro[3,4-d]-1,3-dioxole-5
      carboxylic acid; 1) and 5,7-dimethoxy-aristolochic acid II (= 9,11-dimethoxy-6
      nitrophenantro[3,4-d]-1,3-dioxole-5-carboxylic acid; 2). Exposure to humans of
      some of these compounds is associated with a severe disease today known as
      aristolochic acid nephropathy. Therefore, the traditional usage of this plant has
      to be reconsidered carefully.

PMID- 28499306
TI  - How Are Neonatology Fellows Trained for Antenatal Periviability Counseling?

PMID- 28499307
TI  - Admission Systolic Blood Pressure and Outcomes in Preterm Infants of <= 26 Weeks'
      Gestation.

PMID- 28499308
TI  - Outcome of Neonates with Meconium Aspiration Syndrome at the University Hospital
      of the West Indies, Jamaica: A Resource-Limited Setting.

PMID- 28499309
TI  - Internal Audit of the Canadian Neonatal Network Data Collection System.

PMID- 28499310
TI  - Ellagic Acid Administration Negated the Development of Streptozotocin-Induced
      Memory Deficit in Rats.
AB  - Rampant production of pro-oxidants and inadequate antioxidant availability in
      brain exert oxidative stress, which in synergism with impaired glucose metabolism
      and inflammation leads to neurodegeneration and cognitive deficits. Ellagic acid
      (EGA) is a phenolic compound present in various fruits and is reported to possess
      robust antioxidant and anti-inflammatory properties. The present study
      investigated the effect of EGA administration on streptozotocin (STZ) induced
      dementia in rats. Bilateral intracerebroventricle (ICV) injection of STZ (3
      mg/kg) was given to Wistar rats (200 g) on day 1 and 3. EGA (17.5 and 35 mg/kg)
      was administered orally to rats for 28 days daily. The spatial memory of rats was
      quantified by using Morris water maze and elevated plus maze. Brain TBARS, GSH
      and TNF-alpha were also measured. Administration of EGA prevented the induction
      of STZ-ICV triggered cognitive deficits as evident by a significant (p<0.05)
      reduction in mean escape latency during acquisition trial and increased (p<0.05)
      time spent in target quadrant during retrieval trial in Morris water maze test,
      and reduction (p<0.05) in transfer latency in elevated plus maze test.
      Furthermore, both the doses of EGA attenuated STZ-ICV induced rise in brain TBARS
      as well as TNF-alpha and simultaneously enhanced the GSH content. Thus, EGA
      ameliorated STZ-induced dementia by probably restoring the balance between
      cellular pro-oxidants and anti-oxidants in brain of rats.

PMID- 28499311
TI  - Evaluation of Bone Mineral Density in Children with Type I Diabetes Mellitus and
      Relationship to Serum Levels of Osteopontin.
AB  - Type I diabetes mellitus (T1DM) patients are at risk of osteoporosis and fracture
      due to the osteoblast and osteoclast malfunction. Osteopontin (OPN) as the major
      non-collagenous bone matrix protein is produced by osteoblasts and osteoclasts
      and involve in bone resorption, formation and remodeling. To evaluate the serum
      levels of OPN, bone mineral density (BMD) and correlation in patients with T1DM
      this study was designed. In this case-control study, 87 children with T1DM and 87
      age/sex-matched healthy subjects were enrolled. Blood samples were tested for OPN
      levels by ELISA. Dual energy X-ray absorptiometry was used to measure BMD. The
      mean levels of BMD in patients was significantly lower than control group
      (p<0.0001). There was no significant difference between patients and healthy
      subjects regarding the levels of OPN. However, in patients with high levels of
      OPN (mean+1.5 standard deviation) the BMD was significantly lower than other
      patients (p<0.0001). Totally there was a negative correlation between serum
      levels of OPN and BMD in patients with T1DM (p<0.016). These results indicated
      that the BMD in T1DM is less than healthy children and elevated level of OPN in
      patients could be associated with low BMD. A linear negative correlation between
      serum OPN and total BMD of T1DM patients compared to control group was noticed in
      this study indicating that the amount of serum OPN could be effective on BMD and
      a good predicting factor for osteoporosis in patients.

PMID- 28499312
TI  - Evidence for the Involvement of Monoaminergic Pathways in the Antidepressant-Like
      Activity of Cymbopogon citratus in Mice.
AB  - Objectives Depression is a complex neuropsychiatric disorder, which affects the
      quality of life of the sufferers and treatment approach is associated with
      serious adverse effects and sometimes therapeutic failures. Cymbopogon citratus
      leaf (CC) has been reported to exert anti-depressant effect but its mechanism of
      action is yet to be elucidated hence, the need for this study. Methods The anti
      depressant-like effect of Cymbopogon citratus aqueous leaf was evaluated using
      forced swim test (FST), tail suspension test (TST) and yohimbine-induced
      lethality test (YLT) in aggregated mice. Interaction studies involving p
      chlorophenylalanine (pCPA), an inhibitor of serotonin biosynthesis and yohimbine,
      alpha2-adrenergic receptor antagonist were carried out to evaluate the role of
      monoaminergic system in the anti-depressant-like effect of CC. The effect of CC
      on spontaneous motor activity (SMA) was also assessed using activity cage.
      ResultsCymbopogon citratus (25 and 50 mg/kg, p.o.) demonstrated antidepressant
      like activity devoid of significant stimulation of the SMA in mice. However, the
      antidepressant-like property of CC was significantly (p<0.05) attenuated by
      pretreatment with yohimbine suggesting involvement of noradrenergic pathway in
      the action of the extract. Also, pCPA reversed the anti-immobility effect of CC,
      indicating the role of serotonergic system in the mediation of its antidepressant
      activity. Moreover, CC (25 and 50 mg/kg) potentiated the lethal effect of
      yohimbine in aggregated mice, which further suggest the involvement of
      monoaminergic systems in its action. Conclusions The results of the study showed
      that C. citratus might be interacting with serotonergic and noradrenergic
      pathways to mediate its anti-depressant-like effect in mice.

PMID- 28499313
TI  - [Changes in Tasks and Job Characteristics in Psychiatric-Psychotherapeutic
      Inpatient Treatment in Germany - Description of Relevant Progresses since the
      Commencement of the German "Psychiatry Staff Ordinance" in 1990 - Focusing
      Psychiatric-Psychotherapeutic Inpatient Intensive Care].
AB  - In Germany, mandatory standards in staff job characteristics concerning inpatient
      (clinic and day clinic) treatment in psychiatry and psychotherapy were
      established for the very first time in the year 1990. Those job characteristics,
      concerning the several groups of professionals in German psychiatric
      psychotherapeutic hospitals and departments underwent significant changes causing
      issues of law, professional and socio-cultural development since then. Besides
      general structurally changes, the present article focuses more particularly on
      the field of inpatient psychiatric intensive care therapy.

PMID- 28499314
TI  - [Small Area Variation in Demographic Aging - Informal and Formal Nursing Care
      Ratios and Care Preferences of Senior Citizens Inform Health Care Planners].
AB  - Objective Demographic aging affects the number of older individuals potentially
      in need of care and age groups of younger individuals potentially providing
      formal and informal care. This study examines the current and future demographic
      aging and care preferences on a county level in Saxony. Methods To analyze
      demographic aging, formal (FISR) and informal intergenerational support ratios
      (IISR) based on population data from the Federal Institute for Research on
      Building, Urban Affairs and Spatial Development (BBSR) were used. Ratios were
      calculated for every county in Saxony from 2012 to 2035. Care preferences for
      care settings of senior German citizens in Saxony were determined by a
      representative telephone survey (n = 101; 65+). Results FISR and IISR tend to
      progress in similar ways and are reduced by 50 % by 2035. Regarding nursing care
      preferences, the majority preferred being cared for at home. Implications
      Upcoming care ratios may inform community health care planners and decision
      makers on critical constellations in advance. Strategies to ensure the future
      elderly care are to be developed and implemented.

PMID- 28499315
TI  - [Usual Care for Panic Disorder with/without Agoraphobia in Primary Care].
AB  - OBJECTIVE: To describe therapy as usual (TAU) for panic disorder with/without
      agoraphobia (PDA) in primary care. METHOD: Written survey of 38 general
      practitioners (GPs) who provided TAU to 189 patients with PDA as part of an
      interventional study. Data were analyzed descriptively. RESULTS: The most common
      TAU-interventions were: exploration of psychosocial problems (83 %),
      recommendation not to avoid anxiety-provoking stimuli (72 %), prescription of
      SSRIs (62 %). Common reasons for referrals were various psychiatric comorbidities
      and treatment-refractory anxiety (77 %). GPs rarely used validated diagnostic
      tools such as structured interviews (18 %) or questionnaires (14 %). CONCLUSIONS:
      TAU mostly involved guideline-recommended psychosocial and pharmacological
      interventions. Study-related procedures may limit the generalizability of
      findings.

PMID- 28499316
TI  - [Diagnostic and Prescription Behavior of General Practitioners and Specialist
      Physicians in Patients with Dementia in 2005 and 2015 in Germany].
AB  - RESEARCH QUESTION: Did the diagnostic and treatment behavior of general
      practitioners and specialists in patients with dementia (PWD) change in Germany
      over a period of 11 years (2005 vs. 2015)? METHODS: We performed a retrospective,
      database-based evaluation of diagnostic and prescription data from more than 398
      general practices (GP) and 50 specialist practices (SP). RESULTS: Compared to
      2005, in 2015, the number of PWD had increased by 40.7 % in GP and by 52.4 % in
      SP. The proportion of patients with DAT (Alzheimer's Disease) had increased from
      45.8 % to 61.7 % in SP. The latter changes are different from those in GP, where
      the proportion of patients with DAT had decreased from 20.8 % to 19.2 %. On
      average, each individual GP treated 29.9 PWD in 2015 (2005: 21.3), of which 5.9
      were DAT patients (2005:4.4), and 1.7 DAT patients received an antidementia drug
      (2005: 1.3). On the other hand, an average of 115.4 PWD were diagnosed in SP in
      2015 (2005: 75.7), 71.2 of which were DAT patients (2005: 34.7). 54.4 received an
      antidementia drug (2005: 23.9). CONCLUSIONS: Improvements in the diagnosis of
      dementia and the prescription of antidementia drugs were only found in SP. In
      light of their comparatively low potential for change, whether GP will change
      their diagnostic and treatment behavior in the future and how SP can be better
      integrated into the process of outpatient dementia care remains to be seen.

PMID- 28499317
TI  - [Self-Stigma of Depression Scale SSDS - Evaluation of the German Version].
AB  - OBJECTIVES: A better understanding of self-stigma facilitates the development and
      evaluation of anti-stigma measures. In this study, the Self-Stigma of Depression
      Scale (SSDS) is applied for the first time in Germany. The focus lies on
      feasibility and psychometric characteristics of the scale. METHODS: Data stem
      from a representative population survey in Germany (N = 2,013). The 16 items of
      the original SSDS are used to assess anticipated self-stigma in case of
      depression. Main component analysis is applied to analyze the factor structure.
      RESULTS: The original version of the SDSS could not be replicated in the German
      sample. Instead of four, three factors emerged in the German version. They are
      similar to three subscales of the original SSDS: "social inadequacy", "help
      seeking inhibition" and "self-blame". The internal reliability of the total scale
      as well as of the first two subscales is acceptable. CONCLUSION: SSDS is a
      multidimensional construct and can serve as an important instrument in research
      regarding self-stigma of depression in Germany. A further development of the
      German scale is recommended in order to gain greater insight into the nature of
      (anticipated) depression self-stigma.

PMID- 28499318
TI  - [Psychiatric Inpatient Treatment and Return to Work].
AB  - OBJECTIVE: People with mental diseases have a high risk of unemployment and they
      have only limited access to the labor market. The return to work is often
      associated with fears.The present study aims to provide an overview of the number
      of hospitalized psychiatric patients with permanent employment. Moreover it
      should give an insight into the process of return to work, the experiences
      patients gain and the support they receive. METHODS: In the participating clinics
      we measured the number of patients with permanent employment. The main inclusion
      criteria for further survey were the status of permanent employment and age
      between 18 and 65. The participating patients were interviewed on two occasions,
      at the time of inclusion and 3 months after the patient was discharged. The
      questions addressed working conditions, job satisfaction and the process of
      return-to-work. For statistical analysis, descriptive statistics (frequencies,
      means, standard deviations) were used. RESULTS: Only 21 % of n = 815 inpatients
      of the participating hospitals were permanently employed. Many patients did not
      return to work after being discharged. In many cases the interviewed patients saw
      a connection between their job and their current episode of illness. In this
      context patients reported unsatisfying workplace conditions such as long working
      hours, bad work organization and social conflicts. CONCLUSIONS: For mentally ill
      patients, the employment rate in the primary labor market is devastating low.
      After psychiatric inpatient treatment patients are at high risk to lose their
      jobs. In order to prevent this development, work-related stress factors should be
      discussed with inpatients at an early stage and support should be provided during
      the return-to-work-process.

PMID- 28499319
TI  - [Aftermath of death of a seriously ill family member: Online survey of
      psychological distress and care satisfaction of relatives].
AB  - Aim of the study The aim of the study was to assess the level of psychosocial
      distress and satisfaction with care in family caregivers after the death of a
      close relative. Method Anxiety and depression (HADS) of family caregivers were
      evaluated in both bereaved family caregivers and a comparable group from the
      general population. Furthermore, satisfaction with care (ZUF-8) and social
      support (HOPE-Module, ESSI) were assessed after the patients had died. Regression
      models were employed to analyze associations between psychological distress and
      sociodemographic and care-related variables. Results We conducted an online
      survey with 200 bereaved family caregivers (93% female, time since death of the
      relative: M=306 days). Of these, 31% were the primary caregiver. The bereaved
      caregivers were highly psychologically distressed (high anxiety: 41%/high
      depression: 35%). From the survivors' point of view, care at the end of life was
      partially insufficient: about one in three of the dying patients had suffered
      from pain and 20% had not been treated with dignity. After the relative had
      passed away, 44% of the bereaved caregivers did not get information about support
      offers; one in three missed emotional assistance. Dissatisfaction with care and
      support was associated with increased psychological distress, higher age and a
      shorter period of care. Conclusion The high level of psychological distress in
      bereaved family caregivers suggests high supportive care needs, which are often
      not met in practice. Family caregivers need to be prepared for the time after
      their relative's death and should be offered psychosocial support.

PMID- 28499320
TI  - [Costs of Medial Care of MRSA Patients at the End-of-Life in a Geriatric Ward].
AB  - OBJECTIVE: The present study addresses the financial effects of incidences of
      MRSA in the geriatric ward of a German hospital on patients receiving end-of-life
      care. The main cost drivers will be identified and the costs calculated.
      METHODOLOGY: A retrospective analysis for a period of one year was conducted for
      the geriatric ward of a German hospital. In addition to the duration of the
      patient's stay and the total costs of his/her case, individual cost categories
      such as personnel and material costs were also examined. In order to enable a
      cost comparison of MRSA-positive and MRSA-negative patients, matching was used. T
      tests were used for purposes of comparison with the case groups. FINDINGS: A
      total of 107 cases were included in the study; in 27 of these cases, MRSA was
      detected. Patients with MRSA were found to have a longer average stay and to
      incur higher average costs. There were no statistically significant differences
      in the duration of hospital stay between MRSA-positive and MRSA-negative
      patients. Furthermore, no statistically significant differences were seen in the
      total costs per case. Significantly higher daily personnel costs for nursing
      staff were observed for MRSA-positive patients in the case group of patients with
      lower than average total costs. For MRSA-positive patients, these costs amounted
      to ? 97.18, while MRSA-negative patients incurred ? 80.44 in costs. Costs of
      doctors, medical technicians and non-medical personnel and material costs for
      infrastructure showed an opposite tendency. If the case groups for different
      total costs are not considered, no significant differences between MRSA-positive
      and MRSA-negative patients were found for the individual cost categories
      examined. CONCLUSIONS: Although we demonstrated that MRSA-positive patients had
      longer stays and caused higher overall costs in the geriatric ward, we did not
      find any statistically significant differences between MRSA-positive and MRSA
      negative patients. One of the main cost drivers in the care of MRSA-positive
      patients was identified as the daily personnel costs for nursing staff. Analysing
      processes related to patients' nursing care can be the first step in attempts to
      make care for MRSA-positive patients more effective and efficient.

PMID- 28499321
TI  - [Group Discussions in Health Services Research - Part 1: Introduction and
      Deliberations on Selection of Method and Planning].
AB  - Health services researchers focus on the players, structures and impact of health
      care in "real life". They investigate how social aspects, financing,
      organizational structures, technologies and personal attitudes affect the process
      and outcomes of health care. Qualitative research methods are used here, which
      address how people act according to their unique living conditions (outside the
      context of experimental studies). Different methods of debriefing groups are
      essential for qualitative health services research. In 2 subsequent articles, we
      aim to outline the diverse facets and possible range of implementation of the
      above-mentioned methods, in order to highlight the potential of debriefing groups
      in health services research (focus groups or group discussions) using these
      methods. In the current article, we would like to encourage researchers to
      reflect on relevant topics such as the selection of an appropriate method, the
      planning and undertaking of investigations including sampling methods, and
      questions regarding ethics and privacy. A follow-up article (in preparation) will
      deal with theoretical considerations of the term "group", as well as with the
      process of moderating discussions, methods of analyzing data and (qualitative)
      online research.

PMID- 28499322
TI  - Azathioprine allows glucocorticoid withdrawal - post hoc results of a prospective
      study in patients with inflammatory bowel diseases.
AB  - Background Azathioprine is recommended as first-line immunosuppressant in
      patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data
      on steroid withdrawal after induction therapy in IBD patients are sparse. Methods
      In this post-hoc analysis of a prospective multicenter study, we analyzed the
      proportion and clinical characteristics of 324 azathioprine-tolerant patients as
      to whether they could terminate the glucocorticoid therapy after initiation of
      treatment with azathioprine. Results Systemic steroid therapy was required in 190
      patients (58.6 %) at baseline and in 40 patients (12.3 %) at the end of the
      follow-up period (p < 0.001). The median daily dose was 30 mg at baseline and 10
      mg at follow-up. At baseline, only 122 patients (37.2 %) were advised to take at
      least the lowest recommended dose of 2 mg/kg per day. At follow-up, 221 patients
      (68.2 %) were prescribed at least the recommended maintenance dosage. Conclusion
      The majority of patients with thiopurine-naive IBDs that needed systemic steroids
      at baseline were able to discontinue steroids after 3 - 6 months of azathioprine
      therapy. These data support the continued high value of azathioprine in the
      immunosuppressive therapy of IBD.

PMID- 28499323
TI  - [CMV associated acute liver failure in a patient receiving tocilizumab for
      systemic lupus erythematosus].
AB  - A 41-year-old female patient was admitted because of febrile jaundice and acute
      liver failure. The quick and the bilirubin were 21 % and 258 umol/l, and there
      was hepatic encephalopathy I degrees . AST and AP had a maximum of 612 and 215
      U/l. Despite a strong left shift in the differential, the CRP had a maximum of 15
      mg/l. Because of an atypically presenting systemic lupus erythematosus, she had
      been treated with Azathioprine, steroids and Tocilizumab until 12 days before
      admission. The diagnostic workup revealed CMV hepatitis and necrotizing
      hepatopathy, which was interpreted as toxic hepatitis. At the time of liver
      biopsy, on day 3 after admission, staining for Ki-67 indicated strong
      regenerative activity in the liver. Treatment with Valgancyclovir, antibiotics
      and steroids led to early recovery from liver failure. The case differs from the
      few described cases of severe acute liver injury related to Tocilizumab.
      Apparently, the combined immunosuppression (steroid, Azathioprine and
      Tocilizumab) led to acute liver failure secondary to CMV hepatitis and acute
      toxic hepatitis, which may have been aggravated by transiently impaired liver
      regeneration. On the other hand, stimulated liver regeneration was proven by
      histology despite previous IL6 blockage by Tocilizumab.

PMID- 28499324
TI  - Ascariasis imaging: pictorial essay.
AB  - Ascariasis is not widespread in Europe, and the knowledge on how to diagnose and
      treat the disease is limited to some specialists. On the other hand, clinicians
      are facing an increasing number of immigrants from high-prevalence countries and
      are, therefore, challenged to update in this field of infectious diseases. Here
      we present current knowledge on this infection in 2 parts. The first part
      discusses clinical features and hot topics in ascariasis, and the second part
      presents imaging features of ascariasis as a pictorial essay.

PMID- 28499325
TI  - ?

PMID- 28499326
TI  - ?

PMID- 28499327
TI  - Impact of polyethyleneglycol addition on diffusion coefficients in binary ionic
      liquid electrolytes composed of dicationic ionic liquid and polyethyleneglycol.
AB  - We conduct a comparative study of conductivity and diffusion coefficient of two
      dicationic ionic liquids (3,3'-(octane-1,8-diyl)bis(1-ethyl-3-imidazolium)
      bis(trifluoromethylsulfonyl)amide ([IMCI][TFSI], S1) and 3,3'-(2,2'-(ethane-1,2
      diylbis(oxy))bis(ethane-2,1-diyl))bis(1-ethyl-3-imidazolium)
      bis(trifluoromethylsulfonyl)amide ([IMOI][TFSI], S2)) at various temperatures.
      The diffusion coefficients of cation and anion in ionic liquids are determined by
      using pulse gradient spin-echo nuclear magnetic resonance method. S2 shows lower
      viscosity, higher conductivity, and higher diffusion coefficient than those of
      S1. Moreover, the influence of polyethyleneglycol (PEG200, Mw  = 200) addition in
      PEG200/IL binary solutions is investigated. PEG200/S1 binary solutions show lower
      viscosity, higher conductivity, and higher diffusion coefficient than those of
      neat S1. The experimental molar conductivity (Lambda) of neat IL and PEG200/IL
      binary solutions is lower than that of the calculated molar conductivity
      (LambdaNMR ) from pulse gradient spin-echo nuclear magnetic resonance method at
      various temperatures, indicating that not all the diffusion species belong to the
      ionic conduction. In other words, NMR diffusion measurements comprise charged and
      paired (without charge) ions. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28499328
TI  - Negative psychological consequences of breast cancer among recently diagnosed
      ethnically diverse women.
AB  - OBJECTIVE: Breast cancer has psychological consequences that impact quality of
      life. We examined factors associated with negative psychological consequences of
      a breast cancer diagnosis, in a diverse sample of 910 recently diagnosed patients
      (378 African American, 372 white, and 160 Latina). METHODS: Patients completed an
      in-person interview as part of the Breast Cancer Care in Chicago study within an
      average of 4 months from diagnosis. The Cockburn negative psychological
      consequences of breast cancer screening scale was revised to focus on a breast
      cancer diagnosis. Path analysis assessed predictors of psychological consequences
      and potential mediators between race/ethnicity and psychological consequences.
      RESULTS: Compared to white counterparts, bivariate analysis showed African
      American (beta = 1.4, P < .05) and Latina (beta = 3.6, P < .001) women reported
      greater psychological consequences. Strongest predictors (P < .05 for all)
      included unmet social support (beta = .38), and provider trust (beta = .12),
      followed by stage at diagnosis (beta = .10) and perceived neighborhood social
      disorder (beta = .09).The strongest mediator between race/ethnicity and
      psychological consequences was unmet social support. CONCLUSIONS: African
      American and Latina women reported greater psychological consequences related to
      their breast cancer diagnosis; this disparity was mediated by differences in
      unmet social support. Social support represents a promising point of
      intervention.

PMID- 28499329
TI  - Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage
      Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: To assess performance of the 2016 macrophage activation syndrome (MAS)
      classification criteria for patients with systemic juvenile idiopathic arthritis
      (JIA) who develop MAS while treated with biologic medications. METHODS: A
      systematic literature review was performed to identify patients with MAS while
      being treated with interleukin (IL)-1 and IL-6 blocking agents. Clinical and
      laboratory information was compared to a large previously compiled historical
      cohort. RESULTS: Eighteen publications were identified, and after removing
      duplicates, 35 patients treated with canakinumab and 49 patients with tocilizumab
      were available for analysis; 5 anakinra-treated patients were excluded due to
      limited numbers. MAS classification criteria were less likely to classify
      tocilizumab-treated patients as having MAS compared to the historical cohort or
      canakinumab-treated patients (56.7%, 78.5%, and 84%, respectively; P < 0.01).
      Patients who developed MAS while treated with canakinumab trended towards lower
      ferritin at MAS onset than the historical cohort (4,050 versus 5,353 ng/ml; P =
      0.18) but had no differences in other cardinal clinical or laboratory features.
      In comparison, patients who developed MAS while treated with tocilizumab were
      less likely febrile and had notably lower ferritin levels (1,152 versus 5,353
      ng/ml; P < 0.001). Other features of MAS were more pronounced in patients treated
      with tocilizumab, including lower platelet counts, lower fibrinogen, and higher
      aspartate aminotransferase levels. Mortality rates for patients with MAS treated
      with tocilizumab or canakinumab were not significantly different from the
      historical cohort. CONCLUSION: These findings show substantial alterations in MAS
      features that may limit utility of defined criteria for diagnosis of systemic JIA
      patients treated with biologic agents.

PMID- 28499330
TI  - Ascertaining the impact of public rapid transit system on spread of dengue in
      urban settings.
AB  - Urbanization is an important factor contributing to the global spread of dengue
      in recent decades, especially in tropical regions. However, the impact of public
      transportation system on local spread of dengue in urban settings remains poorly
      understood, due to the difficulty in collecting relevant locality, transportation
      and disease incidence data with sufficient detail, and in suitably quantifying
      the combined effect of proximity and passenger flow. We quantify proximity and
      passenger traffic data relating to 2014-2015 dengue outbreaks in Kaohsiung,
      Taiwan by introducing a "Risk Associated with Metro Passengers Presence" (RAMPP),
      which considers the passenger traffic of stations located within a fixed radius,
      giving more weight to the busier and/or closer stations. In order to analyze the
      contagion risk associated with nearby presence of one or more Kaohsiung Rapid
      Transit (KRT) stations, we cluster the Li's (the fourth level administrative
      subdivision in Taiwan) of Kaohsiung based on their RAMPP value using the K-means
      algorithm. We then perform analysis of variance on distinct clusterings and
      detect significant differences for both years. The subsequent post hoc tests
      (Dunn) show that yearly incidence rate observed in the areas with highest RAMPP
      values is always significantly greater than that recorded with smaller RAMPP
      values. RAMPP takes into account of population mobility in urban settings via the
      use of passenger traffic information of urban transportation system, that
      captures the simple but important idea that large amount of passenger flow in and
      out of a station can dramatically increase the contagion risk of dengue in the
      neighborhood. Our study provides a new perspective in identifying high-risk areas
      for transmissions and thus enhances our understanding of how public rapid transit
      system contributes to disease spread in densely populated urban areas, which
      could be useful in the design of more effective and timely intervention and
      control measures for future outbreaks.

PMID- 28499331
TI  - Correction: Suppression of CD300A inhibits the growth of diffuse large B-cell
      lymphoma.

PMID- 28499332
TI  - Correction: LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/beta
      catenin signalling in neuroblastoma.

PMID- 28499333
TI  - Electrochemical Behavior and Electrodeposition of Nanostructured Rhodium from Low
      Temperature Carbamide and Acetamide Containing Melts.
AB  - The electrochemical behavior of rhodium at low-temperature carbamide-chloride and
      acetamide-chloride melts was investigated. It was found that, during rhodium
      anodic dissolution in carbamide and acetamide containing chloride melts, mixed
      complexes [Rh(NH3)4Cl2]+ of quasi-octahedral symmetry D4h are produced. The
      composition and structure of nascent complex ions have been studied. During
      electrochemical reduction of [Rh(NH3)4Cl2]+ complexes, the synthesis of Rh
      nanoparticles, as well as Fe, Cu, and Mo nanocoatings, were realized.

PMID- 28499335
TI  - Thermal Molding of Organic Thin-Film Transistor Arrays on Curved Surfaces.
AB  - In this work, a thermal molding technique is proposed for the fabrication of
      plastic electronics on curved surfaces, enabling the preparation of plastic films
      with freely designed shapes. The induced strain distribution observed in
      poly(ethylene naphthalate) films when planar sheets were deformed into
      hemispherical surfaces clearly indicated that natural thermal contraction played
      an important role in the formation of the curved surface. A fingertip-shaped
      organic thin-film transistor array molded from a real human finger was
      fabricated, and slight deformation induced by touching an object was detected
      from the drain current response. This type of device will lead to the development
      of robot fingers equipped with a sensitive tactile sense for precision work such
      as palpation or surgery.

PMID- 28499334
TI  - Recent Advances on Neuromorphic Systems Using Phase-Change Materials.
AB  - Realization of brain-like computer has always been human's ultimate dream. Today,
      the possibility of having this dream come true has been significantly boosted due
      to the advent of several emerging non-volatile memory devices. Within these
      innovative technologies, phase-change memory device has been commonly regarded as
      the most promising candidate to imitate the biological brain, owing to its
      excellent scalability, fast switching speed, and low energy consumption. In this
      context, a detailed review concerning the physical principles of the neuromorphic
      circuit using phase-change materials as well as a comprehensive introduction of
      the currently available phase-change neuromorphic prototypes becomes imperative
      for scientists to continuously progress the technology of artificial neural
      networks. In this paper, we first present the biological mechanism of human
      brain, followed by a brief discussion about physical properties of phase-change
      materials that recently receive a widespread application on non-volatile memory
      field. We then survey recent research on different types of neuromorphic circuits
      using phase-change materials in terms of their respective geometrical
      architecture and physical schemes to reproduce the biological events of human
      brain, in particular for spike-time-dependent plasticity. The relevant virtues
      and limitations of these devices are also evaluated. Finally, the future prospect
      of the neuromorphic circuit based on phase-change technologies is envisioned.

PMID- 28499336
TI  - Optical Properties of Gold Nanoparticle Assemblies on a Glass Surface.
AB  - The assemblies of cross-linked gold nanoparticles (AuNP) attract lot of
      scientific attention due to feasible perspectives of their use for development of
      scaled contact electrodes. Here, we developed and tested method of solid-state
      formation of dimers created from small AuNP (~18 nm) cross-linked with 1.9
      nonadithiol (NDT) molecules. The morphology of created coating of a glass surface
      and its optical-polarization properties have been studied in detail by
      combination of scanning electron microscopy, atomic force microscopy, UV-visible
      spectroscopy, and modulation-polarization spectroscopy.The modification of
      localized surface plasmon resonance (LSPR) of single AuNP and their assemblies
      were studied by measuring of the spectral characteristics of polarization
      difference at all stages of synthesis. The radiative and nonradiative modes of
      LSPR have been analyzed in detail at different angles of incidence light. This
      allowed establishing relation between surface morphology of the coating and its
      optical properties.

PMID- 28499337
TI  - Optically Encoded Semiconducting Polymer Dots with Single-Wavelength Excitation
      for Barcoding and Tracking of Single Cells.
AB  - Multiplexed optical encoding is emerging as a powerful technique for high
      throughput cellular analysis and molecular assays. Most of the developed optical
      barcodes, however, either suffer from large particle size or are incompatible
      with most commercial optical instruments. Here, a new type of nanoscale
      fluorescent barcode (Pdot barcodes) was prepared from semiconducting polymers.
      The Pdot barcodes possess the merits of small size (~20 nm in diameter), narrow
      emission bands (full-width-at-half-maximum (fwhm) of 30-40 nm), three-color
      emissions (blue, green, and red) under single-wavelength excitation, a high
      brightness, good pH and thermal stability, and efficient cellular uptake. The
      Pdot barcodes were prepared using a three-color and six-intensity encoding
      strategy; for ratiometric readout of the barcodes, one of the colors might be
      used as an internal reference. We used the Pdot barcodes to label 20 sets of
      cancer cells and then distinguished and identified each set based on the Pdot
      barcodes using flow cytometry. We also monitored and tracked single cells labeled
      with different Pdot barcodes, even through rounds of cell division. These results
      suggest Pdot barcodes are strong candidates for discriminating different labeled
      cell and for long-term cell tracking.

PMID- 28499338
TI  - Hyaluronic Acid Molecular Weight-Dependent Modulation of Mucin Nanostructure for
      Potential Mucosal Therapeutic Applications.
AB  - This study investigates the effects of different molecular weight hyaluronic
      acids (HAs) on the mucosal nanostructure using a pig stomach mucin hydrogel as a
      mucosal barrier model. Microparticles (1.0 MUm) and nanoparticles (200 nm) were
      used as probes, and their movement in mucin was studied by a three-dimensional
      confocal microscopy-based particle tracking technique and by Nanoparticle
      Tracking Analysis (NTA) after addition of high-molecular weight (900 kDa) and low
      molecular weight (33 kDa) HA. This demonstrated a molecular weight-dependent HA
      modulation of the mucin nanostructure with a 2.5-fold decrease in the mobility of
      200 nm nanoparticles. To further investigate these mechanisms and to verify that
      the natural viscoelastic properties of mucus are not undesirably altered,
      rheological measurements were performed on mucin hydrogels with or without HA.
      This suggested the observed particle mobility restriction was not attributed to
      alterations of the natural mucin cohesive and viscoelastic properties but,
      instead, indicates that the added high-molecular weight HA primarily modulates
      the mucin nanostructure and mesh size. This study, hereby, demonstrates how mucus
      nanostructure can be modulated by the addition of high-molecular weight HA that
      offers an opportunity to control mucosal pathogenesis and drug delivery.

PMID- 28499339
TI  - Synthetic Applications and Mechanistic Studies of the Hydroxide-Mediated Cleavage
      of Carbon-Carbon Bonds in Ketones.
AB  - The hydroxide-mediated cleavage of ketones into alkanes and carboxylic acids has
      been reinvestigated and the substrate scope extended to benzyl carbonyl
      compounds. The transformation is performed with a 0.05 M ketone solution in
      refluxing xylene in the presence of 10 equiv of potassium hydroxide. The reaction
      constitutes a straightforward protocol for the synthesis of certain phenyl
      substituted carboxylic acids from 2-phenylcycloalkanones. The mechanism was
      investigated by kinetic experiments which indicated a first order reaction in
      hydroxide and a full negative charge in the rate-determining step. The studies
      were complemented by a theoretical investigation where two possible pathways were
      characterized by DFT/M06-2X. The calculations showed that the scission takes
      place by nucleophilic attack of hydroxide on the ketone followed by fragmentation
      of the resulting oxyanion into the carboxylic acid and a benzyl anion.

PMID- 28499340
TI  - Tebuconazole and Azoxystrobin Residue Behaviors and Distribution in Field and
      Cooked Peanut.
AB  - Residue behaviors of tebuconazole and azoxystrobin in field condition and the
      variation of their residue levels during the boiling process were evaluated. The
      terminal residues of peanut kernels were determined by using a modified QuEChERS
      method (quick, easy, cheap, effective, rugged, and safe) by means of the
      optimization of the novel purification procedure with multiwalled carbon
      nanotubes (MWCNTs) and Fe3O4-magnetic nanoparticle (Fe3O4-MNP) in the presence of
      an external magnetic field, and the terminal residues were all at trace level at
      harvest time. The residues in shells were detected as well to investigate the
      distribution in peanuts. Tebuconazole and azoxystrobin residue levels varied
      before/after boiling in kernels and shells to different degrees due to various
      factors, such as the modes of action and physicochemical properties of
      pesticides. The residues have been transferred from peanut into the infusion
      during boiling with the higher percentage of azoxystrobin as its lower logKow.
      The processing factors (PFs) for tebuconazole and azoxystrobin after processing
      were <1, indicating that home cooking in this study could reduce the residue
      levels in peanut. Risk assessment showed there was no health risk for consumers.

PMID- 28499341
TI  - Positive Detection of GPCR Antagonists Using a System for Inverted Expression of
      a Fluorescent Reporter Gene.
AB  - The yeast Saccharomyces cerevisiae is a useful eukaryotic host organism for
      studying GPCRs as monomolecular models. Fluorescent reporter gene assays for
      GPCRs provide a convenient assay for measuring receptor activity using
      fluorometric instruments. Generally, these assays detect receptor activation by
      agonistic ligands as the induction of fluorescent reporter expression, whereas
      antagonistic activities are detected by competition with agonistic ligands,
      resulting in decreases in fluorescence intensity. In the current study, we
      established a system for inverted expression of a fluorescent reporter by
      incorporating a PEST-tag and finding out a promoter inhibited by activation of
      the GPCR signaling pathway from yeast endogenous promoters. Because agonists
      prevent fluorescent reporter expression in this system, antagonists compete with
      agonists and yield increased fluorescence intensity. We used the yeast endogenous
      pheromone receptor as a model GPCR to demonstrate the feasibility of our system
      for positive detection targeted at antagonists. Compared to results when only
      agonists were added to yeast cells, more than 10-fold higher fluorescence
      intensity was observed when antagonists were added in combination with agonists.
      The approach described here has the potential to markedly accelerate the
      identification of GPCR antagonists by providing rapid and straightforward
      responses.

PMID- 28499342
TI  - Dementia and the privilege of growing old.

PMID- 28499343
TI  - Knee Loading Deficits During Dynamic Tasks in Individuals Following Anterior
      Cruciate Ligament Reconstruction.
AB  - Study Design Controlled laboratory study, cross-sectional. Background Well
      documented deficits in sagittal plane knee loading during dynamic tasks indicate
      that individuals limit the magnitude of knee loading following anterior cruciate
      ligament reconstruction (ACLR). It is unknown how these individuals modulate the
      speed of knee flexion during loading, which is particularly important as they
      progress to running during rehabilitation. Objective To investigate how
      individuals following ACLR perform dynamic knee loading tasks compared to healthy
      controls. Methods Two groups of recreationally active individuals participated:
      15 healthy controls and 15 individuals post-ACLR (ACLR group). Participants
      performed 3 trials of overground running and a single-limb loading (SLL) task.
      Sagittal plane range of motion, peak knee extensor moment, peak knee flexion
      angular velocity, peak knee power absorption, and rate of knee extensor moment
      were calculated during deceleration. A mixed-factor multivariate analysis of
      variance was performed to compare differences in variables between groups (ACLR
      and control), limbs (within ACLR), and tasks (within control). Results Knee power
      absorption, knee flexion angular velocity, and rate of knee extensor moment were
      lower in reconstructed limbs (for the SLL task: 5.6 W/kg, 325.8 degrees /s, and
      10.5 Nm/kg/s, respectively; for running: 11.8 W/kg, 421.4 degrees /s, and 38.2
      Nm/kg/s, respectively) compared to nonsurgical limbs (for the SLL task: 9.7 W/kg,
      432.0 degrees /s, and 19.1 Nm/kg/s, respectively; for running: 18.8 W/kg, 494.1
      degrees /s, and 72.8 Nm/kg/s, respectively) during both tasks (P<.001). The
      magnitudes of between-limb differences in knee flexion angular velocity were
      similar in both tasks. Conclusion Despite lower loading demands during SLL,
      individuals post-ACLR exhibit deficits in knee dynamics during SLL and running,
      suggesting an inability or reluctance to dynamically accommodate forces at the
      knee when progressing to running in rehabilitation. J Orthop Sports Phys Ther
      2017;47(6):411-419. doi:10.2519/jospt.2017.6912.

PMID- 28499344
TI  - The Responsiveness and Minimal Important Change of the Western Ontario Shoulder
      Instability Index and Oxford Shoulder Instability Score.
AB  - Study Design Prospective cohort study. Background Patient-reported outcome
      measurements (PROMs) are widely used to evaluate functional limitations.
      Considering PROMs for shoulder instability, information is lacking with regard to
      what constitutes a relevant change from baseline scores. Objectives To evaluate
      the responsiveness of the Western Ontario Shoulder Instability Index (WOSI) and
      the Oxford Shoulder Instability Score (OSIS) and estimate their minimal important
      change (MIC). Methods One hundred five consecutive patients with shoulder
      instability completed 5 PROMs at baseline and at 6-month follow-up. The PROMs
      included the WOSI and OSIS, the Simple Shoulder Test, the Oxford Shoulder Score,
      and the Disabilities of the Arm, Shoulder and Hand assessment. Patients also
      rated their functional change on an anchor question at follow-up. Responsiveness
      was evaluated by testing 9 hypotheses regarding predefined correlations between
      the changes in PROM scores, by calculating the area under the receiver operating
      characteristic curve and by calculating the standardized response mean and effect
      size statistics. The MIC was determined by identifying the optimal cutoff on the
      receiver operating characteristic curve. Results Seven out of 9 hypotheses (78%)
      were confirmed; as expected, a high correlation (0.77) was found between change
      scores of the WOSI and OSIS, whereas the correlations of the change scores of the
      WOSI and OSIS with those of general shoulder PROMs were slightly lower (0.61
      0.75). The area under the curve was 0.83 (95% confidence interval: 0.75, 0.91)
      for the OSIS and 0.82 (95% confidence interval: 0.74, 0.90) for the WOSI. The MIC
      was about 6 points for the OSIS and about 14 points for the WOSI. Conclusion Both
      the WOSI and OSIS are able to measure change in shoulder function in patients
      with shoulder instability. The estimated MIC is 6 points for the OSIS (on a scale
      from 0 to 48) and 14 points for the WOSI (on a scale from 0 to 100). J Orthop
      Sports Phys Ther 2017;47(6):402-410. doi:10.2519/jospt.2017.6548.

PMID- 28499345
TI  - Exploring the genetic architecture and improving genomic prediction accuracy for
      mastitis and milk production traits in dairy cattle by mapping variants to
      hepatic transcriptomic regions responsive to intra-mammary infection.
AB  - BACKGROUND: A better understanding of the genetic architecture of complex traits
      can contribute to improve genomic prediction. We hypothesized that genomic
      variants associated with mastitis and milk production traits in dairy cattle are
      enriched in hepatic transcriptomic regions that are responsive to intra-mammary
      infection (IMI). Genomic markers [e.g. single nucleotide polymorphisms (SNPs)]
      from those regions, if included, may improve the predictive ability of a genomic
      model. RESULTS: We applied a genomic feature best linear unbiased prediction
      model (GFBLUP) to implement the above strategy by considering the hepatic
      transcriptomic regions responsive to IMI as genomic features. GFBLUP, an
      extension of GBLUP, includes a separate genomic effect of SNPs within a genomic
      feature, and allows differential weighting of the individual marker relationships
      in the prediction equation. Since GFBLUP is computationally intensive, we
      investigated whether a SNP set test could be a computationally fast way to
      preselect predictive genomic features. The SNP set test assesses the association
      between a genomic feature and a trait based on single-SNP genome-wide association
      studies. We applied these two approaches to mastitis and milk production traits
      (milk, fat and protein yield) in Holstein (HOL, n = 5056) and Jersey (JER, n =
      1231) cattle. We observed that a majority of genomic features were enriched in
      genomic variants that were associated with mastitis and milk production traits.
      Compared to GBLUP, the accuracy of genomic prediction with GFBLUP was marginally
      improved (3.2 to 3.9%) in within-breed prediction. The highest increase (164.4%)
      in prediction accuracy was observed in across-breed prediction. The significance
      of genomic features based on the SNP set test were correlated with changes in
      prediction accuracy of GFBLUP (P < 0.05). CONCLUSIONS: GFBLUP provides a
      framework for integrating multiple layers of biological knowledge to provide
      novel insights into the biological basis of complex traits, and to improve the
      accuracy of genomic prediction. The SNP set test might be used as a first-step to
      improve GFBLUP models. Approaches like GFBLUP and SNP set test will become
      increasingly useful, as the functional annotations of genomes keep accumulating
      for a range of species and traits.

PMID- 28499346
TI  - Occupational burnout and empathy influence blood pressure control in primary care
      physicians.
AB  - BACKGROUND: Good physician-patient communication can favor the adoption of
      healthy lifestyle habits, which is essential in high blood pressure (BP)
      management. More empathic physicians tend to have lower burnout and better
      communication skills. We analyzed the association between burnout and empathy
      among primary care physicians and nurses and investigated the influence on BP
      control performance. METHODS: Descriptive study conducted in 2014 investigating
      burnout and empathy levels in 267 primary care physicians and nurses and BP
      control data for 301,657 patients under their care. We administered the Maslach
      Burnout Inventory and the Jefferson Scale of Physician Empathy and defined good
      BP control as a systolic BP <130 mmHg. RESULTS: Low burnout and high empathy were
      observed in 58.8% and 33.7% of practitioners, respectively. Burnout and empathy
      were significantly negatively associated (p < 0.009). Practitioners with high
      empathy and low burnout had significantly better BP control and performance than
      those with low empathy and high burnout (p < 0.05). CONCLUSIONS: Low burnout and
      high empathy were significantly associated with improved BP control and
      performance, possibly in relation to better physician/nurse-patient
      communication.

PMID- 28499347
TI  - The dynamics of early-state transcriptional changes and aggregate formation in a
      Huntington's disease cell model.
AB  - BACKGROUND: Huntington's disease (HD) is a fatal neurodegenerative disorder
      caused by a CAG expansion in the Huntingtin (HTT) gene. Proteolytic cleavage of
      mutant huntingtin (Htt) protein with an expanded polyglutamine (polyQ) stretch
      results in production of Htt fragments that aggregate and induce impaired
      ubiquitin proteasome, mitochondrial functioning and transcriptional
      dysregulation. To understand the time-resolved relationship between aggregate
      formation and transcriptional changes at early disease stages, we performed
      temporal transcriptome profiling and quantification of aggregate formation in
      living cells in an inducible HD cell model. RESULTS: Rat pheochromocytoma (PC12)
      cells containing a stably integrated, doxycycline-inducible, eGFP-tagged N
      terminal human Htt fragment with an expanded polyQ domain were used to analyse
      gene expression changes at different stages of mutant Htt aggregation. At
      earliest time points after doxycycline induction no detectable aggregates and few
      changes in gene expression were observed. Aggregates started to appear at
      intermediate time points. Aggregate formation and subsequent enlargement of
      aggregates coincided with a rapid increase in the number of differentially
      expressed (DE) genes. The increase in number of large aggregates coincided with a
      decrease in the number of smaller aggregates whereas the transcription profile
      reverted towards the profile observed before mutant Htt induction. Cluster-based
      analysis of the 2,176 differentially expressed genes revealed fourteen distinct
      clusters responding differently over time. Functional enrichment analysis of the
      two major gene clusters revealed that genes in the up-regulated cluster were
      mainly involved in metabolic (antioxidant activity and cellular ketone metabolic
      processes) and genes in the down-regulated cluster in developmental processes,
      respectively. Promoter-based analysis of the identified gene clusters resulted in
      identification of a transcription factor network of which several previously have
      been linked to HD. CONCLUSIONS: We demonstrate a time-resolved relationship
      between Htt aggregation and changes in the transcriptional profile. We identified
      two major gene clusters showing involvement of (i) mitochondrial dysfunction and
      (ii) developmental processes implying cellular homeostasis defects. We identified
      novel and known HD-linked transcription factors and show their interaction with
      known and predicted regulatory proteins. Our data provide a novel resource for
      hypothesis building on the role of transcriptional key regulators in early stages
      of HD and possibly other polyQ-dependent diseases.

PMID- 28499348
TI  - Total delay in treatment among tuberculous meningitis patients in China: a
      retrospective cohort study.
AB  - BACKGROUND: Currently, there is limited data on the risk factors associated with
      treatment delay in tuberculous meningitis (TBM). This study aimed to assess the
      duration of delay in the treatment TBM and to investigate its determinants.
      METHODS: During the period from September 2009 to February 2016, a retrospective
      cohort study of consecutive TBM patients admitted to our hospital was conducted
      to determine the risk factors associated with treatment delay in TBM. Treatment
      delay duration was defined as the time interval from onset of symptoms (by
      patient recall) to initiation of treatment and was stratified into two
      categories: <= 20 days, >20 days (median delay day is 20 days). Data collected
      included demography, comorbidity, cerebrospinal fluid (CSF) examinations and
      others. Univariable and multivariable logistic regression analysis was used to
      evaluate the determinants of treatment delay. RESULTS: A total of 161 TBM
      patients were included in our study, all were confirmed by CSF mycobacterial
      culture. The median treatment delay for all patients included in the study was 20
      days [interquartile range, 14-60 days]. Multivariate analysis revealed that age
      (<=21 years old, OR = 0.202, 95% CI: 0.079, 0.521), fever (OR = 0.414, 95% CI:
      0.180, 0.952), and headache (OR = 0.204, 95% CI: 0.095, 0.442) had significantly
      lower risk for treatment delay, while multiple healthcare contact (>3 times) (OR
      = 3.938, 95% CI: 1.326, 11.691) as well as CSF chloride (>111 mmol/L) (OR =
      2.479, 95% CI: 1.143, 5.377) had significantly higher risk of the delay.
      CONCLUSIONS: Our findings indicate that multiple healthcare contact and high CSF
      chloride predict the risk of long delay, while young age, fever and headache are
      associated with short delay. Maintained focus on awareness of TBM in the
      population and in healthcare systems, and continuous implementation of diagnostic
      methods for TBM to detect the disease early, may reduce the mortality and
      morbidity.

PMID- 28499349
TI  - Epimetheus - a multi-profile normalizer for epigenomic sequencing data.
AB  - BACKGROUND: Exponentially increasing numbers of NGS-based epigenomic datasets in
      public repositories like GEO constitute an enormous source of information that is
      invaluable for integrative and comparative studies of gene regulatory mechanisms.
      One of today's challenges for such studies is to identify functionally
      informative local and global patterns of chromatin states in order to describe
      the regulatory impact of the epigenome in normal cell physiology and in case of
      pathological aberrations. Critically, the most preferred Chromatin
      ImmunoPrecipitation-Sequencing (ChIP-Seq) is inherently prone to significant
      variability between assays, which poses significant challenge on comparative
      studies. One challenge concerns data normalization to adjust sequencing depth
      variation. RESULTS: Currently existing tools either apply linear scaling
      corrections and/or are restricted to specific genomic regions, which can be prone
      to biases. To overcome these restrictions without any external biases, we
      developed Epimetheus, a genome-wide quantile-based multi-profile normalization
      tool for histone modification data and related datasets. CONCLUSIONS: Epimetheus
      has been successfully used to normalize epigenomics data in previous studies on X
      inactivation in breast cancer and in integrative studies of neuronal cell fate
      acquisition and tumorigenic transformation; Epimetheus is freely available to the
      scientific community.

PMID- 28499351
TI  - Prediction of the reliability of genomic breeding values for crossbred
      performance.
AB  - BACKGROUND: In crossbreeding programs, various genomic prediction models have
      been proposed for using phenotypic records of crossbred animals to increase the
      selection response for crossbred performance in purebred animals. A possible
      model is a model that assumes identical single nucleotide polymorphism (SNP)
      effects for the crossbred performance trait across breeds (ASGM). Another model
      is a genomic model that assumes breed-specific effects of SNP alleles (BSAM) for
      crossbred performance. The aim of this study was to derive and validate equations
      for predicting the reliability of estimated genomic breeding values for crossbred
      performance in both these models. Prediction equations were derived for
      situations when all (phenotyping and) genotyping data have already been
      collected, i.e. based on the genetic evaluation model, and for situations when
      all genotyping data are not yet available, i.e. when designing breeding programs.
      RESULTS: When all genotyping data are available, prediction equations are based
      on selection index theory. Without availability of all genotyping data,
      prediction equations are based on population parameters (e.g., heritability of
      the traits involved, genetic correlation between purebred and crossbred
      performance, effective number of chromosome segments). Validation of the
      equations for predicting the reliability of genomic breeding values without all
      genotyping data was performed based on simulated data of a two-way crossbreeding
      program, using either two closely-related breeds, or two unrelated breeds, to
      produce crossbred animals. The proposed equations can be used for an easy
      comparison of the reliability of genomic estimated breeding values across many
      scenarios, especially if all genotyping data are available. We show that BSAM
      outperforms ASGM for a specific breed, if the effective number of chromosome
      segments that originate from this breed and are shared by selection candidates of
      this breed and crossbred reference animals is less than half the effective number
      of all chromosome segments that are independently segregating in the same
      animals. CONCLUSIONS: The derived equations can be used to predict the
      reliability of genomic estimated breeding values for crossbred performance using
      ASGM or BSAM in many scenarios, and are thus useful to optimize the design of
      breeding programs. Scenarios can vary in terms of the genetic correlation between
      purebred and crossbred performances, heritabilities, number of reference animals,
      or distance between breeds.

PMID- 28499350
TI  - Transcription factor-associated combinatorial epigenetic pattern reveals higher
      transcriptional activity of TCF7L2-regulated intragenic enhancers.
AB  - BACKGROUND: Recent studies have suggested that combinations of multiple
      epigenetic modifications are essential for controlling gene expression. Despite
      numerous computational approaches have been developed to decipher the
      combinatorial epigenetic patterns or "epigenetic code", none of them has
      explicitly addressed the relationship between a specific transcription factor
      (TF) and the patterns. METHODS: Here, we developed a novel computational method,
      T-cep, for annotating chromatin states associated with a specific TF. T-cep is
      composed of three key consecutive modules: (i) Data preprocessing, (ii) HMM
      training, and (iii) Potential TF-states calling. RESULTS: We evaluated T-cep on a
      TCF7L2-omics data. Unexpectedly, our method has uncovered a novel set of TCF7L2
      regulated intragenic enhancers missed by other software tools, where the
      associated genes exert the highest gene expression. We further used siRNA
      knockdown, Co-transfection, RT-qPCR and Luciferase Reporter Assay not only to
      validate the accuracy and efficiency of prediction by T-cep, but also to confirm
      the functionality of TCF7L2-regulated enhancers in both MCF7 and PANC1 cells
      respectively. CONCLUSIONS: Our study for the first time at a genome-wide scale
      reveals the enhanced transcriptional activity of cell-type-specific TCF7L2
      intragenic enhancers in regulating gene expression.

PMID- 28499352
TI  - Novel optimum contribution selection methods accounting for conflicting
      objectives in breeding programs for livestock breeds with historical migration.
AB  - BACKGROUND: Optimum contribution selection (OCS) is effective for increasing
      genetic gain, controlling the rate of inbreeding and enables maintenance of
      genetic diversity. However, this diversity may be caused by high migrant
      contributions (MC) in the population due to introgression of genetic material
      from other breeds, which can threaten the conservation of small local
      populations. Therefore, breeding objectives should not only focus on increasing
      genetic gains but also on maintaining genetic originality and diversity of native
      alleles. This study aimed at investigating whether OCS was improved by including
      MC and modified kinships that account for breed origin of alleles. Three
      objective functions were considered for minimizing kinship, minimizing MC and
      maximizing genetic gain in the offspring generation, and we investigated their
      effects on German Angler and Vorderwald cattle. RESULTS: In most scenarios, the
      results were similar for Angler and Vorderwald cattle. A significant positive
      correlation between MC and estimated breeding values of the selection candidates
      was observed for both breeds, thus traditional OCS would increase MC.
      Optimization was performed under the condition that the rate of inbreeding did
      not exceed 1% and at least 30% of the maximum progress was achieved for all other
      criteria. Although traditional OCS provided the highest breeding values under
      restriction of classical kinship, the magnitude of MC in the progeny generation
      was not controlled. When MC were constrained or minimized, the kinship at native
      alleles increased compared to the reference scenario. Thus, in addition to
      constraining MC, constraining kinship at native alleles is required to ensure
      that native genetic diversity is maintained. When kinship at native alleles was
      constrained, the classical kinship was automatically lowered in most cases and
      more sires were selected. However, the average breeding value in the next
      generation was also lower than that obtained with traditional OCS. CONCLUSIONS:
      For local breeds with historical introgressions, current breeding programs should
      focus on increasing genetic gain and controlling inbreeding, as well as
      maintaining the genetic originality of the breeds and the diversity of native
      alleles via the inclusion of MC and kinship at native alleles in the OCS process.

PMID- 28499353
TI  - Transposon insertion sequencing reveals T4SS as the major genetic trait for
      conjugation transfer of multi-drug resistance pEIB202 from Edwardsiella.
AB  - BACKGROUND: Conjugation is a major type of horizontal transmission of genes that
      involves transfer of a plasmid into a recipient using specific conjugation
      machinery, which results in an extended spectrum of bacterial antibiotics
      resistance. However, there is inadequate knowledge about the regulator and
      mechanisms that control the conjugation processes, especially in an aquaculture
      environment where a cocktail of antibiotics may be present. Here, we investigated
      these with pEIB202, a typical multi-drug resistant IncP plasmid encoding
      tetracycline, streptomycin, sulfonamide and chloramphenicol resistance in fish
      pathogen Edwardsiella piscicida strain EIB202. RESULTS: We used transposon
      insertion sequencing (TIS) to identify genes that are responsible for conjugation
      transfer of pEIB202. All ten of the plasmid-borne type IV secretion system (T4SS)
      genes and a putative lipoprotein p007 were identified to play an important role
      in pEIB202 horizontal transfer. Antibiotics appear to modulate conjugation
      frequencies by repressing T4SS gene expression. In addition, we identified topA
      gene, which encodes topoisomerase I, as an inhibitor of pEIB202 transfer.
      Furthermore, the RNA-seq analysis of the response regulator EsrB encoded on the
      chromosome also revealed its essential role in facilitating the conjugation by
      upregulating the T4SS genes. CONCLUSIONS: Collectively, our screens unraveled the
      genetic basis of the conjugation transfer of pEIB202 and the influence of
      horizontally acquired EsrB on this process. Our results will improve the
      understanding of the mechanism of plasmid conjugation processes that facilitate
      dissemination of antibiotic resistance especially in aquaculture industries.

PMID- 28499354
TI  - Patient and care characteristics of self-referrals treated by the general
      practitioner cooperative at emergency-care-access-points in the Netherlands.
AB  - BACKGROUND: In the Netherlands, out-of-hours primary care is provided in general
      practitioner-cooperatives (GPCs). These are increasingly located on site and in
      collaboration with emergency departments of hospitals (ED). At such sites, also
      called emergency-care-access-points (ECAP), the GPC is generally responsible for
      the triage and treatment of self-referrals who used to attend the ED. To evaluate
      the effects and safety of this novel organisation, we studied the characteristics
      and the quality of care given by GPCs to self-referrals at ECAPs. METHODS:
      Retrospective analysis (August 2011-January 2012) of 783 records of self-referred
      patients at three Dutch GPCs in an ECAP. This was supplemented with a
      retrospective analysis of patient records during a follow-up period of three
      months to asses safety. RESULTS: Patient-characteristics: 59% was male, 46% aged
      between 16-45 years and 59% trauma-related. Most cases (95%) were triaged low
      urgent. None received the highest urgency-category. Quality: The triage outcome
      was correct in 79%, underestimated in 12% and overestimated in 9%. After GP
      consultation 20% were referred to the ED, mostly for radio-diagnostics. Of the
      referrals to secondary care, 98% were according to common medical practice.
      Thirty percent had a follow-up contact, mostly with their own general
      practitioner, seldom with the ED. Complications, all non-severe, were registered
      in 3.2%; 0.4% were possibly preventable. CONCLUSIONS: Self-referred patients at
      an ECAP are mostly trauma related, low-urgent and male patients. The majority
      could be treated by the GPC without subsequent referral to the ED. Care given at
      the GPC is reasonably efficient and safe. Triage and treatment of self-referrals
      by the GPC at ECAPs might offer opportunities for other countries facing problems
      with inappropriate emergency department visits.

PMID- 28499356
TI  - Erratum to: Out of hours care in Germany - High utilization by adult patients
      with minor ailments?

PMID- 28499355
TI  - Erratum to: Genome-wide association mapping and Identification of candidate genes
      for fatty acid composition in Brassica napus L. using SNP markers.

PMID- 28499357
TI  - Identification of a major Listeria monocytogenes outbreak clone linked to soft
      cheese in Northern Italy - 2009-2011.
AB  - BACKGROUND: Molecular subtyping and enhanced surveillance in Lombardy region
      identified a cluster of possibly related listeriosis cases from 2006 to 2010.
      This cluster grouped 31 isolates that belonged to serotype 1/2a and Sequence Type
      38 (ST38) as defined by Multilocus Sequence Typing (MLST). METHODS: Our study
      expanded the previous investigation to include cases from 2011 to 2014 and used
      Multi-Virulence-Locus Sequence Typing (MVLST) on all ST38 isolates to better
      understand their epidemiology and possibly identify a common source outbreak.
      RESULTS: Out of 306 L. monocytogenes clinical isolates collected, 43 (14.1%)
      belonged to ST38 with cases occurring in nine out of twelve Lombardy provinces.
      The ST38 isolates were split by MVLST into two Virulence Types (VTs): VT80 (n =
      12) and VT104 (n = 31). VT104 cases were concentrated between 2009 and 2011 in
      two provinces, Bergamo and Milan. An epidemiologic investigation was performed
      and in one case, a matching VT104 isolate was retrieved from a soft cheese sample
      from a patient's refrigerator. CONCLUSIONS: Our findings revealed a major
      listeriosis outbreak in Northern Italy linked to soft cheese in 2009-2011, which
      went undetected by local health authorities. Our study shows that integrating
      subtyping methods with conventional epidemiology can help identify the source of
      L. monocytogenes outbreak clones.

PMID- 28499358
TI  - Can we predict functional decline in hospitalized older people admitted through
      the emergency department? Reanalysis of a predictive tool ten years after its
      conception.
AB  - BACKGROUND: In the Emergency Department (ED), early and rapid identification of
      older people at risk of adverse outcomes, who could best benefit from complex
      geriatric intervention, would avoid wasting time, especially in terms of
      prevention of adverse outcomes, and ensure optimal orientation of vulnerable
      patients. We wanted to test the predictive ability of a screening tool assessing
      risk of functional decline (FD), named SHERPA, 10 years after its conception, and
      to assess the added value of other clinical or biological factors associated with
      FD. METHODS: A prospective cohort study of older patients (n = 305, >= 75 years)
      admitted through the emergency department, for at least 48 h in non-geriatric
      wards (mean age 82.5 +/- 4.9, 55% women). SHERPA variables (i.e. age, pre
      admission instrumental Activity of Daily Living (ADL) status, falls within a
      year, self-rated health and 21-point MMSE) were collected within 48 h of
      admission, along with socio-demographic, medical and biological data. Functional
      status was followed at 3 months by phone. FD was defined as a decrease at 3
      months of at least one point in the pre-admission basic ADL score. Predictive
      ability of SHERPA was assessed using c-statistic, predictive values and
      likelihood ratios. Measures of discrimination improvement were Net
      Reclassification Improvement and Integrated Discrimination Improvement. RESULTS:
      One hundred and five patients (34%) developed 3-month FD. Predictive ability of
      SHERPA decreased dramatically over 10 years (c = 0.73 vs. 0.64). Only two of its
      constitutive variables, i.e. falls and instrumental ADL, were significant in
      logistic regression analysis for functional decline, while 21-point MMSE was kept
      in the model for clinical relevance. Demographic, comorbidity or laboratory data
      available upon admission did not improve the SHERPA predictive yield.
      CONCLUSIONS: Prediction of FD with SHERPA is difficult, but predictive factors,
      i.e. falls, pre-existing functional limitation and cognitive impairment, stay
      consistent across time and with literature. As accuracy of SHERPA and others
      existing screening tools for FD is moderate, using these predictors as flags
      instead of using composite scales can be a way to screen for high-risk patients.

PMID- 28499359
TI  - Cystic fibrosis carriership and tuberculosis: hints toward an evolutionary
      selective advantage based on data from the Brazilian territory.
AB  - BACKGROUND: The reason why Cystic Fibrosis (CF) is the most common fatal genetic
      disease among Caucasians has been incompletely studied. We aimed at deepening the
      hypothesis that CF carriers have a relative protection against Mycobacterium
      tuberculosis (Mtb) infection. METHODS: Applying spatial epidemiology, we studied
      the link between CF carriership rate and tuberculosis (TB) incidence in Brazil.
      We corrected for 5 potential environmental and 2 immunological confounders in
      this relation: monthly income, sanitary provisions, literacy rates, racial
      composition and population density along with AIDS incidence rates and diabetes
      mellitus type 2. Smoking data were incomplete and not available for analysis.
      RESULTS: A significant, negative correlation between CF carriership rate and TB
      incidence, independent of any of the seven confounders was found. CONCLUSION: We
      provide exploratory support for the hypothesis that carrying a single CFTR
      mutation arms against Mtb infections.

PMID- 28499360
TI  - Prevalence and correlates of cognitive impairment in kidney transplant
      recipients.
AB  - BACKGROUND: There is a high prevalence of cognitive impairment in dialysis
      patients. The prevalence of cognitive impairment after kidney transplantation is
      unknown. METHODS: Study Design: Cross-sectional study. SETTING AND PARTICIPANTS:
      Single center study of prevalent kidney transplant recipients from a transplant
      clinic in a large academic center. INTERVENTION: Assessment of cognition using
      the Montreal Cognitive Assessment (MoCA). Demographic and clinical variables
      associated with cognitive impairment were also examined. Outcomes and
      Measurements: a) Prevalence of cognitive impairment defined by a MoCA score of
      <26. b) Multivariable linear and logistic regression to examine the association
      of demographic and clinical factors with cognitive impairment. RESULTS: Data from
      226 patients were analyzed. Mean (SD) age was 54 (13.4) years, 73% were white,
      60% were male, 37% had diabetes, 58% had an education level of college or above,
      and the mean (SD) time since kidney transplant was 3.4 (4.1) years. The
      prevalence of cognitive impairment was 58.0%. Multivariable linear regression
      demonstrated that older age, male gender and absence of diabetes were associated
      with lower MoCA scores (p < 0.01 for all). Estimated glomerular filtration rate
      (eGFR) was not associated with level of cognition. The logistic regression
      analysis confirmed the association of older age with cognitive impairment.
      CONCLUSION: Cognitive impairment is common in prevalent kidney transplant
      recipients, at a younger age compared to general population, and is associated
      with certain demographic variables, but not level of eGFR.

PMID- 28499361
TI  - Dietary diversity scores: an indicator of micronutrient inadequacy instead of
      obesity for Chinese children.
AB  - BACKGROUND: Micronutrient malnutrition affects the well-being of both adults and
      children. Dietary diversity score (DDS) is a useful evaluation index with a
      relatively well-developed guideline by FAO. It's meaningful to assess and predict
      inadequate micronutrient intakes using DDS in Chinese children, after ruling out
      the risk of obesity coming with more dietary diversity. METHODS: Data for
      evaluation were extracted from the Nutrition Study of Preschool Children and
      School Children, which is a cross-sectional study covering 8 cities of China,
      including 1694 children in kindergartens and primary schools. This study applied
      DDS to Chinese children to test the validity for micronutrient inadequacy, and
      then explored the relationship between dietary diversity and obesity. RESULTS: It
      reveals that dietary diversity varied with age and place of residence; the older
      ones and the ones living in rural areas tend to have poorer dietary diversity.
      Another discovery is that DDS is positively correlated with indicators of
      micronutrient adequacy, with a score of 6-8 indicating the lowest risk of
      micronutrient inadequacy in different groups of children. In our study
      population, dietary diversity is not related with obesity. CONCLUSIONS: Dietary
      diversity score is a valid indicator to evaluate micronutrient inadequacy in
      Chinese children, though there is still room for improvement of the method.
      Besides, the relationship between increase of dietary diversity and risk of
      obesity should be treated circumspectly.

PMID- 28499362
TI  - Active delivery of the anterior arm and incidence of second-degree perineal
      tears: a clinical practice evaluation.
AB  - BACKGROUND: Evaluate the feasibility of active delivery of the anterior arm
      during spontaneous delivery. This maneuver could decrease incidence of second
      degree perineal tears because it reduces fetal biacromial diameter. METHODS: An
      observational comparative prospective study was conducted at our teaching
      maternity from July 2012 to March 2013. The study included 199 nulliparous women
      >=18 years, who met the following criteria: singleton pregnancy, vaginal delivery
      with occiput anterior presentation, on epidural analgesia, from 37 weeks of
      gestation onward. The distribution of rate and type of perineal tears were
      compared between two groups: a non-exposed group and a group exposed to the
      maneuver. RESULTS: A total of 101 patients were exposed to Couder's maneuver (CM)
      and 98 patients were not exposed. In the intervention group, 3 failures of the
      maneuver were reported. The maneuver was considered easy in 80% of cases,
      moderately easy in 12% and difficult in 8% of cases. There was a significant
      difference (p = 0.03) in the distribution of perineal tears between the two
      groups. There was a significant reduction (p < 0.001) in the number of second
      degree perineal tears in the patients exposed to CM. There was no significant
      difference in the rate of anterior perineal trauma between the exposed and non
      exposed arms. CONCLUSIONS: CM in primiparous women at term is feasible with a low
      failure rate and influences the distribution of perineal tears by lowering second
      degree perineal tears in a highly significant manner (p <0.01).

PMID- 28499363
TI  - Predictors of response to prefabricated foot orthoses or rocker-sole footwear in
      individuals with first metatarsophalangeal joint osteoarthritis.
AB  - BACKGROUND: Osteoarthritis of the first metatarsophalangeal joint (1st MTPJ OA)
      is a common and disabling condition commonly managed with footwear and orthotic
      interventions. The objective of this study was to identify factors associated
      with a successful treatment response in people with 1st MTPJ OA provided with
      prefabricated orthoses or rocker-sole footwear as part of a randomised clinical
      trial. METHODS: People with 1st MTPJ OA (n = 88) who participated in a randomised
      trial were allocated to receive prefabricated foot orthoses (n = 47) or rocker
      sole footwear (n = 41) and completed a baseline questionnaire including
      information on demographics, anthropometrics, general health, pain
      characteristics (including the Foot Health Status Questionnaire [FHSQ] and Foot
      Function Index [FFI]) and perceptions of the interventions, and a clinical
      assessment of foot posture, range of motion, radiographic severity and in-shoe
      plantar pressures. Adherence was documented using diaries. At 12 weeks,
      participants documented their perception of improvement on a 15-point scale.
      Those reporting at least moderate improvement on this scale were classified as
      'responders'. RESULTS: There were 29 responders (62%) in the orthoses group and
      16 responders (39%) in the rocker-sole group. In the orthoses group, responders
      had greater baseline pain severity while walking, a higher FFI difficulty score,
      and wore their orthoses more frequently. In the rocker-sole group, responders had
      a higher FFI stiffness score and greater radiographic severity. However, the
      accuracy of these variables in identifying responders in each group was modest
      (62 and 53%, respectively). CONCLUSION: The response to prefabricated orthoses or
      rocker-sole footwear in people with 1st MTPJ OA is related to measures of
      increased pain and disease severity. However, the overall classification accuracy
      associated with these factors is not sufficient for identifying individuals who
      are most likely to benefit from these interventions. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry: ACTRN12613001245785.

PMID- 28499364
TI  - Clinical classification in low back pain: best-evidence diagnostic rules based on
      systematic reviews.
AB  - BACKGROUND: Clinical examination findings are used in primary care to give an
      initial diagnosis to patients with low back pain and related leg symptoms. The
      purpose of this study was to develop best evidence Clinical Diagnostic Rules
      (CDR] for the identification of the most common patho-anatomical disorders in the
      lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone,
      muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous
      system sensitization. METHODS: A sensitive electronic search strategy using
      MEDLINE, EMBASE and CINAHL databases was combined with hand searching and
      citation tracking to identify eligible studies. Criteria for inclusion were:
      persons with low back pain with or without related leg symptoms, history or
      physical examination findings suitable for use in primary care, comparison with
      acceptable reference standards, and statistical reporting permitting calculation
      of diagnostic value. Quality assessments were made independently by two reviewers
      using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical
      examination findings that were investigated by at least two studies were included
      and results that met our predefined threshold of positive likelihood ratio >= 2
      or negative likelihood ratio <= 0.5 were considered for the CDR. RESULTS: Sixty
      four studies satisfied our eligible criteria. We were able to construct promising
      CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis,
      disc herniation with nerve root involvement, and spinal stenosis. Single clinical
      test appear not to be as useful as clusters of tests that are more closely in
      line with clinical decision making. CONCLUSIONS: This is the first comprehensive
      systematic review of diagnostic accuracy studies that evaluate clinical
      examination findings for their ability to identify the most common patho
      anatomical disorders in the lumbar spine. In some diagnostic categories we have
      sufficient evidence to recommend a CDR. In others, we have only preliminary
      evidence that needs testing in future studies. Most findings were tested in
      secondary or tertiary care. Thus, the accuracy of the findings in a primary care
      setting has yet to be confirmed.

PMID- 28499365
TI  - Investigation of DNA repair-related SNPs underlying susceptibility to papillary
      thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children
      exposed to radiation.
AB  - BACKGROUND: Genetic factors may influence an individual's sensitivity to ionising
      radiation and therefore modify his/her risk of developing papillary thyroid
      carcinoma (PTC). Previously, we reported that common single nucleotide
      polymorphisms (SNPs) within the DNA damage recognition gene ATM contribute to PTC
      risk in Belarusian children exposed to fallout from the Chernobyl power plant
      accident. Here we explored in the same population the contribution of a panel of
      DNA repair-related SNPs in genes acting downstream of ATM. METHODS: The
      association of 141 SNPs located in 43 DNA repair genes was examined in 75 PTC
      cases and 254 controls from the Gomel region in Belarus. All subjects were
      younger than 15 years at the time of the Chernobyl accident. Conditional logistic
      regressions accounting for radiation dose were performed with PLINK using the
      additive allelic inheritance model, and a linkage disequilibrium (LD)-based
      Bonferroni correction was used for correction for multiple testing. RESULTS: The
      intronic SNP rs2296675 in MGMT was associated with an increased PTC risk [per
      minor allele odds ratio (OR) 2.54 95% CI 1.50, 4.30, P per allele = 0.0006, P
      corr.= 0.05], and gene-wide association testing highlighted a possible role for
      ERCC5 (P Gene = 0.01) and PCNA (P Gene = 0.05) in addition to MGMT (P Gene =
      0.008). CONCLUSIONS: These findings indicate that several genes acting in
      distinct DNA repair mechanisms contribute to PTC risk. Further investigation is
      needed to decipher the functional properties of the methyltransferase encoded by
      MGMT and to understand how alteration of such functions may lead to the
      development of the most common type of thyroid cancer.

PMID- 28499366
TI  - The role of BRCA1-IRIS in the development and progression of triple negative
      breast cancers in Egypt: possible link to disease early lesion.
AB  - BACKGROUND: Breast cancer is the most globally diagnosed female cancer, with the
      triple negative breast cancer (TNBC) being the most aggressive subtype of the
      disease. In this study we aimed at comparing the effect of BRCA1-IRIS
      overexpression on the clinico-pathological characteristics in breast cancer
      patients with TNBC or non-TNBC in the largest comprehensive cancer center in
      Egypt. METHODS: To reach this goal, we conducted an observational study at the
      National Cancer Institute (NCI), Cairo University (Cairo, Egypt). The data on all
      diagnosed breast cancer patients, between 2009 and 2012, were reviewed. BRCA1
      IRIS expression measured using real time RT/PCR in these patients' tumor samples
      was correlated to tumor characteristics, such as to clinico-pathological
      features, therapeutic responses, and survival outcomes. RESULTS: 96 patients were
      enrolled and of these 45% were TNBC, and 55% were of other subtypes (hereafter,
      non-TNBC). All patients presented with invasive ductal carcinomas. No significant
      difference was observed for risk factors, such as age and menopausal status
      between the TNBC and the non-TNBC groups except after BRCA1-IRIS expression was
      factored in. The majority of the tumors in both groups were <=5 cm at surgery (p
      = 0.013). However, in the TNBC group, <=5 cm tumors were BRCA1-IRIS
      overexpressing, whereas in the non-TNBC group they were BRCA1-IRIS-negative (p =
      0.00007). Most of the TNBC patients diagnosed with grade 1 or 2 were BRCA1-IRIS
      overexpressing, whereas non-TNBCs were IRIS-negative (p = 0.00035). No
      statistical significance was measured in patients diagnosed with grade 3 tumors.
      Statistically significant difference between TNBCs and non-TNBCs and tumor stage
      with regard to BRCA1-IRIS-overexpression was observed. Presence of axillary lymph
      node metastases was positively associated with BRCA1-IRIS overexpression in TNBC
      group, and with BRCA1-IRIS-negative status in the non-TNBC group (p = 0.00009).
      Relapse after chemotherapy (p < 0.00001), and local recurrence/distant metastasis
      after surgery (p = 0.0028) were more pronounced in TNBC patients with BRCA1-IRIS
      overexpressing tumors compared to non-TNBC patients. Finally, decreased disease
      free survival in TNBC/BRCA1-IRIS-overexpressing patients compared to TNBC/BRCA1
      IRIS-negative patients, and decreased overall survival in TNBC as well as non
      TNBC patients was driven by BRCA1-IRIS overexpression. CONCLUSIONS: TNBC/BRCA1
      IRIS-overexpressing tumors are more aggressive than TNBC/BRCA1-IRIS-negative or
      non-TNBC/BRCA1-IRIS-overexpressing or both negative tumors. Further studies are
      warranted to define whether BRCA1-IRIS drives the early TNBC lesions growth and
      dissemination and whether it could be used as a diagnostic biomarker and/or
      therapeutic target for these lesions at an early stage setting.

PMID- 28499367
TI  - The effectiveness of long-needle acupuncture at acupoints BL30 and BL35 for
      CP/CPPS: a randomized controlled pilot study.
AB  - BACKGROUND: The chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one
      of the commonest chronic inflammatory diseases in adult men, for which
      acupuncture has been used to relieve related symptoms. The present study aimed to
      evaluate the therapeutic effect of the long-needle acupuncture on CP/CPPS.
      METHODS: A randomized traditional acupuncture-controlled single blind study was
      conducted on 77 patients who were randomized into long-needle acupuncture (LA)
      and traditional acupuncture (TA) groups. The patients received six sessions of
      acupuncture for 2 weeks and a follow-up was scheduled at week 24. The primary
      outcome was measured by the total National Institutes of Health-Chronic
      Prostatitis Symptom Index (NIH-CPSI) score at week 2. Four domains of the NIH
      CPSI (urination, pain or discomfort, effects of symptoms, and quality of life)
      and the clinical efficacy score served as the secondary outcome. RESULTS: The
      total NIH-CPSI score at week 2 and week 24 was significantly improved in the LA
      group compared with the TA group. LA significantly improved urination, pain or
      discomfort, the effects of symptoms, and the quality of life at week 2 and week
      24 and patients undergoing LA treatment had a higher clinical efficacy score.
      CONCLUSION: Needling at the BL30 and BL35 using LA benefits patients with
      CP/CPPS. TRIAL REGISTRATION: The study was registered at the Chinese Clinical
      Trial Register ( ChiCTR-ICR-15006138 ).

PMID- 28499368
TI  - Measuring mental well-being in Norway: validation of the Warwick-Edinburgh Mental
      Well-being Scale (WEMWBS).
AB  - BACKGROUND: Mental well-being is an important, yet understudied, area of
      research, partly due to lack of appropriate population-based measures. The
      Warwick-Edinburgh Mental Well-being Scale (WEMWBS) was developed to meet the
      needs for such a measure. This article assesses the psychometric properties of
      the Norwegian version of the WEMWBS, and its short-version (SWEMWBS) among a
      sample of primary health care patients who participated in the evaluation of
      Prompt Mental Health Care (PMHC), a novel Norwegian mental health care program
      aimed to increase access to treatment for anxiety and depression. METHODS:
      Forward and back-translations were conducted, and 1168 patients filled out an
      electronic survey including the WEMWBS, and other mental health scales. The
      original dataset was randomly divided into a training sample (~70%) and a
      validation sample (~30%). Parallel analysis and confirmatory factor analysis were
      carried out to assess construct validity and precision. The final models were
      cross-validated in the validation sample by specifying a model with fixed
      parameters based on the estimates from the trainings set. Criterion validity and
      measurement invariance of the (S)WEMWBS were examined as well. RESULTS: Support
      was found for the single factor hypothesis in both scales, but similar to
      previous studies, only after a number of residuals were allowed to correlate
      (WEMWBS: CFI = 0.99; RMSEA = 0.06, SWEMWBS: CFI = .99; RMSEA = 0.06). Further
      analyses showed that the correlated residuals did not alter the meaning of the
      underlying construct and did not substantially affect the associations with other
      variables. Precision was high for both versions of the WEMWBS (>.80), and scalar
      measurement invariance was obtained for gender and age group. The final
      measurement models displayed adequate fit statistics in the validation sample as
      well. Correlations with other mental health scales were largely in line with
      expectations. No statistically significant differences were found in mean latent
      (S)WEMWBS scores for age and gender. CONCLUSION: Both WEMWBS scales appear to be
      valid and precise instruments to measure mental well-being in primary health care
      patients. The results encourage the use of mental well-being as an outcome in
      future epidemiological, clinical, and evaluation studies, and may as such be
      valuable for both research and public health practice.

PMID- 28499369
TI  - Characterization of a splice-site mutation in the tumor suppressor gene FLCN
      associated with renal cancer.
AB  - BACKGROUND: Renal cell carcinoma is among the most prevalent malignancies. It is
      generally sporadic. However, genetic studies of rare familial forms have led to
      the identification of mutations in causative genes such as VHL and FLCN.
      Mutations in the FLCN gene are the cause of Birt-Hogg-Dube syndrome, a rare tumor
      syndrome which is characterized by the combination of renal cell carcinoma,
      pneumothorax and skin tumors. METHODS: Using Sanger sequencing we identify a
      heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient
      suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a
      metastasis are analyzed regarding this mutation. The pathogenic effect of the
      sequence alteration is confirmed by minigene assays and the biochemical
      consequences on the protein are examined using TALEN-mediated transgenesis in
      cultured cells. RESULTS: Here we describe an FLCN mutation in a 55-year-old
      patient who presented himself with progressive weight loss, bilateral kidney
      cysts and renal tumors. He and members of his family had a history of recurrent
      pneumothorax during the last few decades. Histology after tumor nephrectomy
      showed a mixed kidney cancer consisting of elements of a chromophobe renal cell
      carcinoma and dedifferentiated small cell carcinoma component. Subsequent FLCN
      sequencing identified an intronic c.1177-5_-3delCTC alteration that most likely
      affected the correct splicing of exon 11 of the FLCN gene. We demonstrate
      skipping of exon 11 to be the consequence of this mutation leading to a shift in
      the reading frame and the insertion of a premature stop codon. Interestingly, the
      truncated protein was still expressed both in cell culture and in tumor tissue,
      though it was strongly destabilized and its subcellular localization differed
      from wild-type FLCN. Both, altered protein stability and subcellular localization
      could be partly reversed by blocking proteasomal and lysosomal degradation.
      CONCLUSIONS: Identification of disease-causing mutations in BHD syndrome requires
      the analysis of intronic sequences. However, biochemical validation of the
      consecutive alterations of the resulting protein is especially important in these
      cases. Functional characterization of the disease-causing mutations in BHD
      syndrome may guide further research for the development of novel diagnostic and
      therapeutic strategies.

PMID- 28499371
TI  - "Placebo effect is probably what we refer to as patient healing power": A
      qualitative pilot study examining how Norwegian complementary therapists reflect
      on their practice.
AB  - BACKGROUND: Complementary therapists spend considerable time with their patients,
      especially in the first consultation. The communication between patients and
      their therapists is important for raising consciousness and activation of the
      patient's self-healing power. Thus, the aims in this study were to delineate what
      complementary therapists regard as essential in patient consultations, their view
      of the healing process, and how the therapists understand the placebo effect and
      its position in the healing process. METHODS: Semi-structured individual
      interviews (n = 4), focus group interview (n = 1) and participant observation
      were conducted among four different complementary therapists in a Norwegian
      community. The text data was transcribed verbatim and the analysis of the
      material was conducted according to conventional and direct content analysis.
      Some codes were predefined and others were defined during the analysis. RESULTS:
      The pilot study showed that the implemented methods seems feasible and fit well
      with the aims of this study. Complementary therapists (chiropractor, naprapath
      (musculoskeletal therapist), acupuncturist and acupuncturist/homeopath)
      representing four different complementary modalities participated. A combination
      of the conversation and examination during the first consultation formed the
      basis for the therapist's choice of treatment. A successful consultation was
      characterized by a fruitful relationship between the therapist and the patient.
      Moreover, the therapist needs to be humble and show the patient respect.
      Patients' positive beliefs and expectations about the treatment play a
      significant role in the healing process. The more hope the therapist can bring
      about, the more easily the patient can start believing that it is possible to get
      well. CONCLUSION: This was a pilot study. Therefore the findings should be
      appreciated as limited and preliminary. Therapists' and patients' mutual
      understanding and treatment goals were essential for a successful consultation.
      The therapists emphasized their professional skills and therapeutic competence as
      important when building fruitful relationships with their patients. Exerting
      authority and making the patient feel confident were essential factors for a
      successful healing process. The complementary therapists understood the placebo
      effect as the patient's self-healing power, resulting from establishing trust and
      belief in the treatment process.

PMID- 28499370
TI  - Is hydroxychloroquine effective in treating primary Sjogren's syndrome: a
      systematic review and meta-analysis.
AB  - BACKGROUND: To systematically review and assess the efficacy and safety of
      hydroxychloroquine (HCQ) for treating primary Sjogren's syndrome (pSS). METHODS:
      Five electronic databases (Pubmed, EMBASE, Web of science, Ovid, Cochrane
      Library) were searched for randomized controlled trials and retrospective or
      prospective studies published in English that reported the effect of HCQ on pSS.
      The subjective symptoms ( sicca symptoms, fatigue and pain) and the objective
      indexes (erythrocyte sedimentation rate and Schirmer test) were assessed as main
      outcome measures. A meta-analysis and descriptive study on the efficacy and
      safety of HCQ were conducted. The estimate of the effect of HCQ treatment was
      expressed as a proportion together with 95% confidence interval, and plotted on a
      forest plot. RESULTS: Four trials with totals of 215 SS patients, including two
      randomized controlled trials, one double blind crossover trial and one
      retrospective open-label study, were analyzed in this review. For dry mouth and
      dry eyes, the effectiveness of HCQ treatment was essentially the same as placebo
      treatment. For fatigue, the effectiveness of HCQ was lower than placebo. The
      efficacy of HCQ in treating pain associated with pSS was superior to that of the
      placebo. There was no significant difference between HCQ-treated groups and
      controls in terms of Schirmer test results, but HCQ could reduce the erythrocyte
      sedimentation rate compare with placebo. A descriptive safety assessment showed
      that gastrointestinal adverse effects were the most common adverse effects
      associated with HCQ. CONCLUSIONS: This systematic review showed that there is no
      significant difference between HCQ and placebo in the treatment of dry mouth and
      dry eye in pSS. Well-designed, randomized, controlled trials are needed to
      provide higher-quality evidence to confirm our findings, and future studies
      should focus on some other  i n dex  or  extraglandular measures, such as
      cutaneous manifestations, to further explore the therapeutic effect of HCQ in
      pSS.

PMID- 28499372
TI  - Persons with rheumatoid arthritis challenge the relevance of the health
      assessment questionnaire: a qualitative study of patient perception.
AB  - BACKGROUND: The Stanford Health Assessment Questionnaire-Disability Index (HAQ)
      is widely used to measure functional ability in persons with Rheumatoid Arthritis
      (RA). The instrument was developed with limited involvement from persons with RA,
      and their perception of the instrument has not been studied in depth. The aim of
      this study was to explore how persons with RA experience the use of the HAQ in
      care. METHODS: The study used secondary data analysis. Persons with RA
      participated in semi-structured interviews in previous research projects. Thirty
      nine interviews were included based on data fit, and thematic analysis applied.
      RESULTS: The participants questioned the relevance of the HAQ but nevertheless
      experienced that the instrument had a profound effect on their understanding of
      health and how care is delivered. The analysis resulted in three themes: Problems
      with individual items, meaning of the summative score, and effects on care and
      health perceptions. CONCLUSIONS: To make the HAQ relevant to persons with RA, it
      needs to be revised or to include an option to select items most meaningful to
      the respondent. To ensure relevance, the HAQ update should preferably be co
      created by researchers, clinicians and persons with RA.

PMID- 28499373
TI  - A case-control study of selenoprotein genes polymorphisms and autoimmune thyroid
      diseases in a Chinese population.
AB  - BACKGROUND: Selenium is an essential trace and there is a high selenium
      concentration in the thyroid gland. Selenium deficiency may impair the thyroid
      function. The aim of this study was to investigate the association between three
      selenoprotein genes polymorphisms and autoimmune thyroid diseases. METHODS: We
      genotyped six single-nucleotide polymorphisms (SNPs), rs6865453 in selenoprotein
      P gene (SELENOP), rs713041 rs2074451 rs3746165 in glutathione peroxidase 4 gene
      (GPX4) and rs28665122 and rs7178239 in selenoprotein S gene (SELENOS) by
      MassARRAY system using the chip-based matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry technology in 1060 patients with autoimmune
      thyroid diseases and 938 healthy controls. RESULTS: Major alleles in rs6865453 of
      SELENOP, rs713041, rs2074451, rs3746165 of GPX4 decreased while the major allele
      C in rs28665122 of SELENOS increased in AITD patients than in the control. The
      allele C and genotype CC in rs7178239 of SELENOS showed different trend in GD and
      HT patients when compared with the control. All the distribution difference
      showed nonsignificant. Analysis according to clinical features including
      ophthalmopathy, hypothyroidism and family history came out to be negative either.
      CONCLUSIONS: Our findings suggest non-association between three selenoprotein
      genes and AITD, conflicting to the positive result in another population.
      Different selenium nutrition status in different populations may contribute to
      conflicting results, the contribution of genetic variants in AITD mechanism may
      be another reason.

PMID- 28499374
TI  - Clinical improvement of renal amyloidosis in a patient with systemic-onset
      juvenile idiopathic arthritis who received tocilizumab treatment: a case report
      and literature review.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is a common rheumatic disease in
      children and adolescents. Although JIA may cause secondary amyloidosis, this is a
      rare complication in patients with JIA and other rheumatic diseases. Many
      previous studies have revealed that common heterozygous or homozygous mutations
      in the MEFV gene are associated with systemic-onset JIA (SJIA). CASE
      PRESENTATION: We herein report a case involving a 19-year-old female patient with
      difficult-to-control SJIA. She developed progressive proteinuria without clinical
      signs or symptoms of edema. Renal amyloidosis was diagnosed by renal pathologic
      examination, which demonstrated deposition of eosinophilic amorphous material in
      the interlobular arteries, arterioles, and interstitium. Electron microscopy
      showed fibrillary material deposits with a diameter of 8 to 10 nm. A heterozygous
      E148Q mutation in the MEFV gene was identified. Conventional disease-modifying
      anti-rheumatic drugs and etanercept had been used to treat the SJIA, but the
      disease could not be controlled. Therefore, we decided to start tocilizumab to
      control the disease activity. However, the patient was unable to receive a
      standard dose of tocilizumab in the early period of treatment because of
      socioeconomic limitations. Her disease course was still active, and proteinuria
      was found. Therefore, tocilizumab was increased to a dose of 8 mg/kg every 2
      weeks (standard dose of SJIA), and the patient exhibited a clinical response
      within 3 months. CONCLUSION: Refractory SJIA associated with renal amyloidosis is
      an uncommon cause of proteinuria in adolescents. Tocilizumab may be a beneficial
      treatment for renal amyloidosis in patients with SJIA.

PMID- 28499375
TI  - Cardiovascular risk status of Afro-origin populations across the spectrum of
      economic development: findings from the Modeling the Epidemiologic Transition
      Study.
AB  - BACKGROUND: Cardiovascular risk factors are increasing in most developing
      countries. To date, however, very little standardized data has been collected on
      the primary risk factors across the spectrum of economic development. Data are
      particularly sparse from Africa. METHODS: In the Modeling the Epidemiologic
      Transition Study (METS) we examined population-based samples of men and women,
      ages 25-45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural
      Ghana, Cape Town, South Africa, and the Seychelles. Key measures of
      cardiovascular disease risk are described. RESULTS: The risk factor profile
      varied widely in both total summary estimates of cardiovascular risk and in the
      magnitude of component factors. Hypertension ranged from 7% in women from Ghana
      to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with
      a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women
      total cholesterol values varied relatively little by country, following between
      160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in
      men and women from all study sites. Obesity ranged from 64% among women in the US
      to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based
      on the Framingham risk score a clear trend toward higher total risk in
      association with socioeconomic development was observed among men, while among
      women there was considerable overlap, with the US participants having only a
      modestly higher risk score. CONCLUSIONS: These data provide a comprehensive
      estimate of cardiovascular risk across a range of countries at differing stages
      of social and economic development and demonstrate the heterogeneity in the
      character and degree of emerging cardiovascular risk. Severe
      hypercholesterolemia, as characteristic in the US and much of Western Europe at
      the onset of the coronary epidemic, is unlikely to be a feature of the
      cardiovascular risk profile in these countries in the foreseeable future,
      suggesting that stroke may remain the dominant cardiovascular event.

PMID- 28499376
TI  - Benefits of preparing for childbirth with mindfulness training: a randomized
      controlled trial with active comparison.
AB  - BACKGROUND: Childbirth fear is linked with lower labor pain tolerance and worse
      postpartum adjustment. Empirically validated childbirth preparation options are
      lacking for pregnant women facing this problem. Mindfulness approaches, now
      widely disseminated, can alleviate symptoms of both chronic and acute pain and
      improve psychological adjustment, suggesting potential benefit when applied to
      childbirth education. METHODS: This study , the Prenatal Education About Reducing
      Labor Stress (PEARLS) study, is a randomized controlled trial (RCT; n = 30) of a
      short, time-intensive, 2.5-day mindfulness-based childbirth preparation course
      offered as a weekend workshop , the Mind in Labor (MIL): Working with Pain in
      Childbirth, based on Mindfulness-Based Childbirth and Parenting (MBCP) education.
      First-time mothers in the late 3rd trimester of pregnancy were randomized to
      attend either the MIL course or a standard childbirth preparation course with no
      mind-body focus. Participants completed self-report assessments pre-intervention,
      post-intervention, and post-birth, and medical record data were collected.
      RESULTS: In a demographically diverse sample, this small RCT demonstrated
      mindfulness-based childbirth education improved women's childbirth-related
      appraisals and psychological functioning in comparison to standard childbirth
      education. MIL program participants showed greater childbirth self-efficacy and
      mindful body awareness (but no changes in dispositional mindfulness), lower post
      course depression symptoms that were maintained through postpartum follow-up, and
      a trend toward a lower rate of opioid analgesia use in labor. They did not,
      however, retrospectively report lower perceived labor pain or use epidural less
      frequently than controls. CONCLUSIONS: This study suggests mindfulness training
      carefully tailored to address fear and pain of childbirth may lead to important
      maternal mental health benefits, including improvements in childbirth-related
      appraisals  and  the prevention of postpartum depression symptoms. There is also
      some indication that MIL participants may use mindfulness coping in lieu of
      systemic opioid pain medication. A large-scale RCT that captures real-time pain
      perceptions during labor and length of labor is warranted to provide a more
      definitive test of these effects. TRIAL REGISTRATION: The ClinicalTrials.gov
      identifier for the PEARLS  study is: NCT02327559 . The study was retrospectively
      registered on June 23, 2014.

PMID- 28499377
TI  - Calculating hospital length of stay using the Hospital Episode Statistics; a
      comparison of methodologies.
AB  - BACKGROUND: Accurate calculation of hospital length of stay (LOS) from the
      English Hospital Episode Statistics (HES) is important for a wide range of audit
      and research purposes. The two methodologies which are commonly used to achieve
      this differ in their accuracy and complexity. We compare these methods and make
      recommendations on when each is most appropriate. METHODS: We calculated LOS
      using continuous inpatient spells (CIPS), which link care spanning across
      multiple hospitals, and spells, which do not, for six conditions with short
      (dyspepsia or other stomach function, ENT infection), medium (dehydration and
      gastroenteritis, perforated or bleeding ulcer), and long (stroke, fractured
      proximal femur) average LOS. We examined how inter-area comparisons (i.e.
      benchmarking) and temporal trends differed. We defined a classification system
      for spells and explored the causes of differences. RESULTS: Stroke LOS was 16.5
      days using CIPS but 24% (95% CI: 23, 24) lower, at 12.6 days, using spells.
      Smaller differences existed for shorter-LOS conditions including dehydration and
      gastroenteritis (4.5 vs. 4.2 days) and ENT infection (0.9 vs. 0.8 days). Typical
      patient pathways differed markedly between areas and have evolved over time. One
      area had the third shortest stroke LOS (out of 151) using spells but the fourth
      longest using CIPS. These issues were most profound for stroke and fractured
      proximal femur, as patients were frequently transferred to a separate hospital
      for rehabilitation, however important disparities also existed for conditions
      with simpler secondary care pathways (e.g. ENT infections, dehydration and
      gastroenteritis). CONCLUSIONS: Spell-based LOS is widely used by researchers and
      national reporting organisations, including the Health and Social Care
      Information Centre, however it can substantially underestimate the time patients
      spend in hospital. A widespread shift to a CIPS methodology is required to
      improve the quality of LOS estimates and the robustness of research and
      benchmarking findings. This is vital when investigating clinical areas with
      typically long, complex patient pathways. Researchers should ensure that their
      LOS calculation methodology is fully described and explicitly acknowledge
      weaknesses when appropriate.

PMID- 28499378
TI  - Organisational systems' approaches to improving cultural competence in
      healthcare: a systematic scoping review of the literature.
AB  - INTRODUCTION: Healthcare organisations serve clients from diverse Indigenous and
      other ethnic and racial groups on a daily basis, and require appropriate client
      centred systems and services for provision of optimal healthcare. Despite
      advocacy for systems-level approaches to cultural competence, the primary focus
      in the literature remains on competency strategies aimed at health promotion
      initiatives, workforce development and student education. This paper aims to
      bridge the gap in available evidence about systems approaches to cultural
      competence by systematically mapping key concepts, types of evidence, and gaps in
      research. METHODS: A literature search was completed as part of a larger
      systematic search of evaluations and measures of cultural competence
      interventions in health care in Canada, the United States, Australia and New
      Zealand. Seventeen peer-reviewed databases, 13 websites and clearinghouses, and
      11 literature reviews were searched from 2002 to 2015. Overall, 109 studies were
      found, with 15 evaluating systems-level interventions or describing measurements.
      Thematic analysis was used to identify key implementation principles,
      intervention strategies and outcomes reported. RESULTS: Twelve intervention and
      three measurement studies met our inclusion criteria. Key principles for
      implementing systems approaches were: user engagement, organisational readiness,
      and delivery across multiple sites. Two key types of intervention strategies to
      embed cultural competence within health systems were: audit and quality
      improvement approaches and service-level policies or strategies. Outcomes were
      found for organisational systems, the client/practitioner encounter, health, and
      at national policy level. DISCUSSION AND IMPLICATIONS: We could not determine the
      overall effectiveness of systems-level interventions to reform health systems
      because interventions were context-specific, there were too few comparative
      studies and studies did not use the same outcome measures. However, examined
      together, the intervention and measurement principles, strategies and outcomes
      provide a preliminary framework for implementation and evaluation of systems
      level interventions to improve cultural competence. Identified gaps in the
      literature included a need for cost and effectiveness studies of systems
      approaches and explication of the effects of cultural competence on client
      experience. Further research is needed to explore the extent to which cultural
      competence improves health outcomes and reduces ethnic and racially-based
      healthcare disparities.

PMID- 28499379
TI  - Diet with a combination of high protein and high total antioxidant capacity is
      strongly associated with low prevalence of frailty among old Japanese women: a
      multicenter cross-sectional study.
AB  - BACKGROUND: The intake of protein and antioxidants has been inversely associated
      with frailty, individually. However, to our knowledge, no study has evaluated
      these associations in considering antioxidants or protein intakes as respective
      confounders. Further, the cooperative effect of dietary protein and antioxidants
      on frailty has not been investigated. Therefore, we examined the association of
      high protein and high dietary total antioxidant capacity (TAC) with frailty under
      the adjustment for dietary TAC or protein intake, respectively. The association
      between the combination of high dietary protein and high dietary TAC and frailty
      was also investigated. METHODS: A total of 2108 grandmothers or acquaintances of
      dietetic students aged 65 years and older participated in this cross-sectional
      multicenter study conducted in 85 dietetic schools in Japan. Dietary variables,
      including protein intake, and dietary TAC were estimated from a validated brief
      type self-administered diet history questionnaire. Frailty was defined as a score
      of three or more points obtained from the following four components: slowness and
      weakness (two points), exhaustion, low physical activity, and unintentional
      weight loss. RESULTS: Median (interquartile range) age of the present subjects
      was 74 (71-78) years. Multivariate adjusted ORs (95% CIs) for frailty in the
      highest compared to the lowest tertile were 0.66 (0.49, 0.87) for total protein
      intake (P for trend = 0.003) and 0.51 (0.37, 0.69) for dietary TAC (P for trend
      <0.0001) after adjustment for dietary TAC or total protein intake, respectively.
      The OR of frailty for the group with both the highest tertiles of total protein
      intake and dietary TAC was markedly lower (multivariate adjusted OR [95% CIs]:
      0.27 [0.16, 0.44]; P <0.0001) compared to the group with the lowest tertile of
      protein intake and the lowest tertile of dietary TAC. CONCLUSIONS: Both protein
      intake and dietary TAC were independently inversely associated with frailty among
      old Japanese women. Further, a diet with the combination of high dietary protein
      and high dietary TAC was strongly inversely associated with the prevalence of
      frailty in this population. To select food combinations that allow for an
      increase of both protein and antioxidants in diet according to the local food
      culture and dietary habits may be an effective strategy for frailty prevention.

PMID- 28499380
TI  - Erratum to: Implementing 360 degrees  Quantified Self for childhood obesity:
      feasibility study and experiences from a weight loss camp in Qatar.

PMID- 28499381
TI  - Experience in the use of non-pneumatic anti-shock garment (NASG) in the
      management of postpartum haemorrhage with hypovolemic shock in the Fundacion
      Valle Del Lili, Cali, Colombia.
AB  - BACKGROUND: The aim of this case series is to describe the experience of using
      the non-pneumatic anti-shock garment (NASG) in the management of severe
      Postpartum hemorrhage (PPH) and shock, and the value of implementing this concept
      in high-complexity obstetric hospitals. METHODS: Descriptive case series of 77
      women that received NASG in the management of PPH with severe hypovolemic shock
      from June 2014 to December 2015. Vital signs, shock index (SI), the lactic acid
      value and the base deficit were compared before and after NASG application.
      RESULTS: Fifty-six (77%) women had an SI > 1.1 at the time shock management was
      initiated; 96% had uterine atony. All women received standard does of
      uterotonics. The average time between the birth and NASG applications was 20 min.
      Forty-eight percent of women recovered haemodynamic variables in the first hour
      and 100% within the first 6 h; 100% had a SI < 1.0 in the first hour. The NASG
      was not removed until definitive control of bleeding was achieved, with an
      average time of use of 24 h. There were no mortalities. CONCLUSIONS: In this case
      series of women in severe shock, the NASG was an effective management device for
      the control of severe hypovolemic shock. It should be considered a first-line
      option for shock management.

PMID- 28499382
TI  - The association between residential eviction and syringe sharing among a
      prospective cohort of street-involved youth.
AB  - BACKGROUND: Syringe sharing is a high-risk practice associated with the
      transmission of infectious diseases, such as HIV and HCV. While youth who contend
      with housing instability are known to be more likely to engage in high-risk
      substance use, the potential relationship between being evicted from housing and
      syringe sharing has not been examined. This study assessed whether residential
      eviction was associated with syringe sharing among street-involved youth in
      Vancouver, Canada. METHODS: Data were derived from the At-Risk Youth Study
      (ARYS), a prospective cohort of street-involved youth who use drugs age 14-26 in
      Vancouver, Canada. The study period was June 2007 to May 2014, and the potential
      relationship between residential eviction and syringe sharing was analyzed using
      multivariable generalized estimating equations (GEE) logistic regression.
      RESULTS: Among 405 street-involved youth who injected drugs, 149 (36.8%) reported
      syringe sharing, defined as borrowing or lending a syringe, at some point during
      the study period. In a multivariable GEE analysis, recent residential eviction
      remained independently associated with syringe sharing (adjusted odds ratio (AOR)
      = 1.72, 95% confidence interval (CI): 1.16-2.57), after adjusting for potential
      confounders. CONCLUSIONS: Syringe sharing was significantly elevated among youth
      who had recently been evicted from housing. These findings indicate that policy
      and programmatic interventions that increase housing stability may help mitigate
      high-risk substance use practices among vulnerable youth.

PMID- 28499383
TI  - Nintedanib antiangiogenic inhibitor effectiveness in delaying adenocarcinoma
      progression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP).
AB  - BACKGROUND: In recent times, anti-cancer treatments have focused on Fibroblast
      Growth Factor (FGF) and Vascular-Endothelial Growth Factor (VEGF) pathway
      inhibitors so as to target tumor angiogenesis and cellular proliferation. One
      such drug is Nintedanib; the present study evaluated the effectiveness of
      Nintedanib treatment against in vitro proliferation of human prostate cancer
      (PCa) cell lines, and growth and progression of different grades of PCa lesions
      in pre-clinical PCa transgenic adenocarcinoma for the mouse prostate (TRAMP)
      model. METHODS: Both androgen-independent (LNCaP) and androgen-dependent (PC3)
      PCa cell lines were treated with a range of Nintedanib doses for 72 h, and effect
      on cell growth and expression of angiogenesis associated VEGF receptors was
      analyzed. In pre-clinical efficacy evaluation, male TRAMP mice starting at 8 and
      12 weeks of age were orally-fed with vehicle control (10% Tween 20) or Nintedanib
      (10 mg/Kg/day in vehicle control) for 4 weeks, and sacrificed immediately after 4
      weeks of drug treatment or sacrificed 6-10 weeks after stopping drug treatments.
      At the end of treatment schedule, mice were sacrificed and ventral lobe of
      prostate was excised along with essential metabolic organ liver, and subjected to
      histopathological and extensive molecular evaluations. RESULTS: The total cell
      number decreased by 56-80% in LNCaP and 45-93% in PC3 cells after 72 h of
      Nintedanib treatment at 2.5-25 MUM concentrations. In pre-clinical TRAMP studies,
      Nintedanib led to a delay in tumor progression in all treatment groups; the
      effect was more pronounced when treatment was given at the beginning of the
      glandular lesion development and continued till study end. A decreased
      microvessel density and VEGF immunolocalization was observed, besides decreased
      expression of Androgen Receptor (AR), VEGFR-1 and FGFR-3 in some of the treated
      groups. No changes were observed in the histological liver analysis. CONCLUSIONS:
      Nintedanib treatment was able to significantly decrease the growth of PCa cell
      lines and also delay growth and progression of PCa lesions to higher grades of
      malignancy (without inducing any hepatotoxic effects) in TRAMP mice. Furthermore,
      it was observed that Nintedanib intervention is more effective when administered
      during the early stages of neoplastic development, although the drug is capable
      of reducing cell proliferation even after treatment interruption.

PMID- 28499384
TI  - Quality of care in family planning services in Senegal and their outcomes.
AB  - BACKGROUND: High quality of care in family planning (FP) services has been found
      to be associated with increased and continued use of contraceptive methods. The
      interpersonal skills and technical competence of the provider is one of the main
      components of quality of care. To study the process component of quality of care,
      the distribution of the FP counseling topics was examined by client, provider and
      facility characteristics. To assess the outcomes of quality of care, client
      satisfaction and their knowledge of their method's protection from STIs were
      used. This study examined the factors associated with these outcomes with a focus
      on provider counseling and training. METHODS: Data from the 2012-2013 Senegal
      Service Provision Assessment survey was used for the analysis. The survey
      included a representative sample of the health facilities in Senegal and collects
      data by observing the clients' FP visits and conducting exit interviews. The main
      outcomes of interest were provider's counseling in FP, client's satisfaction with
      FP services and client's knowledge of their method's protection from STIs.
      Several covariates were used in the analysis which represent client, provider and
      facility characteristics. RESULTS: The level of counseling was inadequate-- very
      low proportions of providers that performed different types of counseling.
      Counseling was more likely to be provided to new than returning clients.
      Approximately 84% of the clients were very satisfied with services but only 58%
      had correct knowledge of their method's protection from STIs. Clients were
      significantly less likely to be very satisfied when their providers counseled on
      side effects and when to return, and counseling provided on method's protection
      from STIs did not significantly improve knowledge in this area. Clients seen by a
      provider with FP training had almost twice the odds of having correct knowledge
      about their method's protection from STIs compared with clients seen by a
      provider with no recent training. CONCLUSIONS: The percentage of providers
      offering FP counseling to their clients was relatively low and was ineffective on
      the client-focused outcomes. Interventions may be required for more effective
      counseling methods that are client-centered as well as providing more FP training
      to providers.

PMID- 28499385
TI  - Target organ damage and incident type 2 diabetes mellitus: the Strong Heart
      Study.
AB  - BACKGROUND: Recent analyses in a registry of hypertensive patients suggested that
      preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis
      are associated with incident type 2 diabetes, independent of confounders. We
      assess the relation between prevalent cardio-renal target organ damage (TOD) and
      subsequent incident type 2 diabetes in a population-based study with high
      prevalence of obesity. METHODS: We selected 2887 non-diabetic participants from
      two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and
      echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA)
      dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable
      logistic regression models were used to identify variables responsible for the
      association between initial TODs and incident diabetes at 4-year follow-up (FU).
      RESULTS: After 4 years, 297 new cases of diabetes (10%) were identified, 216 of
      whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001).
      Participants developing type 2 diabetes exhibited higher inflammatory markers,
      fat-free mass and adipose mass and higher prevalence of initial LVH and LA
      dilatation than those without (both p < 0.04). In multivariable logistic
      regression, controlling for age, sex, family relatedness, presence of arterial
      hypertension and IFG, all three indicators of TOD predicted incident diabetes
      (all p < 0.01). However, the effects of TOD was offset when body fat and
      inflammatory markers were introduced into the model. CONCLUSIONS: In this
      population-based study with high prevalence of obesity, TOD precedes clinical
      appearance of type 2 diabetes and is related to the preceding metabolic status,
      body composition and inflammatory status. Trial registration Trial registration
      number: NCT00005134, Name of registry: Strong Heart Study, URL of registry:
      https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25,
      2000, Date of enrolment of the first participant to the trial: September 1988.

PMID- 28499386
TI  - Gender equality and human rights approaches to female genital mutilation: a
      review of international human rights norms and standards.
AB  - Two hundred million girls and women in the world are estimated to have undergone
      female genital mutilation (FGM), and another 15 million girls are at risk of
      experiencing it by 2020 in high prevalence countries (UNICEF, 2016. Female
      genital mutilation/cutting: a global concern. 2016). Despite decades of concerted
      efforts to eradicate or abandon the practice, and the increased need for clear
      guidance on the treatment and care of women who have undergone FGM, present
      efforts have not yet been able to effectively curb the number of women and girls
      subjected to this practice (UNICEF. Female genital mutilation/cutting: a
      statistical overview and exploration of the dynamics of change. 2013), nor are
      they sufficient to respond to health needs of millions of women and girls living
      with FGM. International efforts to address FGM have thus far focused primarily on
      preventing the practice, with less attention to treating associated health
      complications, caring for survivors, and engaging health care providers as key
      stakeholders. Recognizing this imperative, WHO developed guidelines on management
      of health complications of FGM. In this paper, based on foundational research for
      the development of WHO's guidelines, we situate the practice of FGM as a rights
      violation in the context of international and national policy and efforts, and
      explore the role of health providers in upholding health-related human rights of
      women at girls who are survivors, or who are at risk. Findings are based on a
      literature review of relevant international human rights treaties and UN Treaty
      Monitoring Bodies.

PMID- 28499387
TI  - Evolution of the "fourth stage" of epidemiologic transition in people aged 80
      years and over: population-based cohort study using electronic health records.
AB  - BACKGROUND: In the "fourth stage" of epidemiological transition, the distribution
      of non-communicable diseases is expected to shift to more advanced ages, but age
      specific changes beyond 80 years of age have not been reported. METHODS: This
      study aimed to evaluate demographic and health transitions in a population aged
      80 years and over in the United Kingdom from 1990 to 2014, using primary care
      electronic health records. Epidemiological analysis of chronic morbidities and
      age-related impairments included a cohort of 299,495 participants, with
      stratified sampling by five-year age group up to 100 years and over. Cause
      specific proportional hazards models were used to estimate hazard ratios for
      incidence rates over time. RESULTS: Between 1990 and 2014, nonagenarians and
      centenarians increased as a proportion of the over-80 population, as did the male
      to-female ratio among individuals aged 80 to 95 years. A lower risk of coronary
      heart disease (HR 0.54, 95% confidence interval [CI]: 0.50-0.58), stroke (0.83,
      0.76-0.90) and chronic obstructive pulmonary disease (0.59, 0.54-0.64) was
      observed among 80-84 year-olds in 2010-2014 compared to 1995-1999. By contrast,
      the risk of type II diabetes (2.18, 1.96-2.42), cancer (1.52, 1.43-1.61),
      dementia (2.94, 2.70-3.21), cognitive impairment (5.57, 5.01-6.20), and
      musculoskeletal pain (1.26, 1.21-1.32) was greater in 2010-2014 compared to 1995
      1999. CONCLUSIONS: Redistribution of the over-80 population to older ages, and
      declining age-specific incidence of cardiovascular and respiratory diseases in
      over-80s, are consistent with the "fourth stage" of epidemiologic transition, but
      increases in diabetes, cancer, and age-related impairment show new emerging
      epidemiological patterns in the senior elderly.

PMID- 28499388
TI  - Frequent use of hospital inpatient services during a nine year period: a
      retrospective cohort study.
AB  - BACKGROUND: Frequent use (FU) of hospital services impacts on patients and health
      service expenditure. Studies examining FU in emergency departments and inpatient
      settings have found heterogeneity and the need to differentiate between
      potentially preventable FU and that associated with ongoing management of complex
      conditions. Psychosocial factors have often been reported as underpinning or
      exacerbating the phenomena. Most FU studies have been limited by time, to a
      single study site, or restricted to specific diagnoses or patient groups. This
      study provides a comprehensive description of adult patient characteristics,
      conditions and risk factors associated with FU, based on admissions to the five
      public hospitals in the Northern Territory (NT) of Australia over a nine year
      period. The study population is distinctive comprising both Aboriginal and non
      Aboriginal patients. METHODS: Data on all inpatient episodes in NT public
      hospitals between 2005 and 2013 was analysed to identify patients with any FU
      (four or more episodes within any 12-month period) and measure FU duration
      (number of FU years) and intensity (mean number of episodes per FU year).
      Pregnancy, alcohol-related and mental health condition flags were assigned to
      patients with any episode with relevant diagnoses during the study period.
      Multivariate analysis was used to assess factors associated with any FU, FU
      duration and FU intensity, separately for Aboriginal and non-Aboriginal patients.
      RESULTS: Of people with any inpatient episodes during the study period, 13.6%
      were frequent users (Aboriginal 22%, non-Aboriginal 10%) accounting for 46.6% of
      all episodes. 73% of frequent users had only one FU year. Any FU and increased FU
      duration were more common among individuals who were: Aboriginal; older; female;
      and those with a pregnancy, alcohol or mental health flag. Having two or more
      alcohol-related episodes in the nine-year period was strongly associated with any
      FU for both Aboriginal (odds ratio 8.9, 95% CI. 8.20-9.66) and non-Aboriginal
      patients (11.5, 9.92-13.26). CONCLUSION: For many people, frequent inpatient
      treatment is necessary and unavoidable. This study suggests that damage arising
      from excessive alcohol consumption (either personal or by others) is the single
      most avoidable factor associated with FU, particularly for Aboriginal people.

PMID- 28499389
TI  - A phase II trial of autologous dendritic cell vaccination and radiochemotherapy
      following fluorescence-guided surgery in newly diagnosed glioblastoma patients.
AB  - BACKGROUND: Prognosis of patients with glioblastoma multiforme (GBM) remains
      dismal, with median overall survival (OS) of about 15 months. It is therefore
      crucial to search alternative strategies that improve these results obtained with
      conventional treatments. In this context, immunotherapy seems to be a promising
      therapeutic option. We hypothesized that the addition of tumor lysate-pulsed
      autologous dendritic cells (DCs) vaccination to maximal safe resection followed
      by radiotherapy and concomitant and adjuvant temozolomide could improve patients'
      survival. METHODS: We conducted a phase-II clinical trial of autologous DCs
      vaccination in patients with newly diagnosed patients GBM who were candidates to
      complete or near complete resection. Candidates were finally included if residual
      tumor volume was lower than 1 cc on postoperative radiological examination.
      Autologous DCs were generated from peripheral blood monocytes and pulsed with
      autologous whole tumor lysate. The vaccination calendar started before
      radiotherapy and was continued during adjuvant chemotherapy. Progression free
      survival (PFS) and OS were analyzed with the Kaplan-Meier method. Immune response
      were assessed in blood samples obtained before each vaccines. RESULTS: Thirty-two
      consecutive patients were screened, one of which was a screening failure due to
      insufficient resection. Median age was 61 years (range 42-70). Karnofsky
      performance score (KPS) was 90-100 in 29%, 80 in 35.5% and 60-70 in 35.5% of
      cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in
      45.2% of patients. No severe adverse effects related to immunotherapy were
      registered. Median PFS was 12.7 months (CI 95% 7-16) and median OS was 23.4
      months (95% CI 16-33.1). Increase in post-vaccination tumor specific immune
      response after vaccines (proliferation or cytokine production) was detected in
      11/27 evaluated patients. No correlation between immune response and survival was
      found. CONCLUSIONS: Our results suggest that the addition of tumor lysate-pulsed
      autologous DCs vaccination to tumor resection and combined radio-chemotherapy is
      feasible and safe. A multicenter randomized clinical trial is warranted to
      evaluate the potential survival benefit of this therapeutic approach. Trial
      registration This phase-II trial was registered as EudraCT: 2009-009879-35 and
      ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.

PMID- 28499390
TI  - High-content behavioral profiling reveals neuronal genetic network modulating
      Drosophila larval locomotor program.
AB  - BACKGROUND: Two key questions in understanding the genetic control of behaviors
      are: what genes are involved and how these genes interact. To answer these
      questions at a systems level, we conducted high-content profiling of Drosophila
      larval locomotor behaviors for over 100 genotypes. RESULTS: We studied 69 genes
      whose C. elegans orthologs were neuronal signalling genes with significant
      locomotor phenotypes, and conducted RNAi with ubiquitous, pan-neuronal, or motor
      neuronal Gal4 drivers. Inactivation of 42 genes, including the nicotinic
      acetylcholine receptors nAChRalpha1 and nAChRalpha3, in the neurons caused
      significant movement defects. Bioinformatic analysis suggested 81 interactions
      among these genes based on phenotypic pattern similarities. Comparing the worm
      and fly data sets, we found that these genes were highly conserved in having
      neuronal expressions and locomotor phenotypes. However, the genetic interactions
      were not conserved for ubiquitous profiles, and may be mildly conserved for the
      neuronal profiles. Unexpectedly, our data also revealed a possible motor-neuronal
      control of body size, because inactivation of Rdl and Galphao in the motor
      neurons reduced the larval body size. Overall, these data established a framework
      for further exploring the genetic control of Drosophila larval locomotion.
      CONCLUSIONS: High content, quantitative phenotyping of larval locomotor
      behaviours provides a framework for system-level understanding of the gene
      networks underlying such behaviours.

PMID- 28499391
TI  - Safety of three different product doses in autologous chondrocyte implantation:
      results of a prospective, randomised, controlled trial.
AB  - BACKGROUND: This study was conducted to assess the efficacy and safety of the
      three dose levels of the three-dimensional autologous chondrocyte implantation
      product chondrosphere(r) in the treatment of cartilage defects (4-10 cm2) of knee
      joints. We hereby report the safety results for a 36-month post-treatment
      observation period. METHODS: This was a prospective phase II trial with a
      clinical intervention comprising biopsy for culturing spheroids and their
      subsequent administration (level of evidence: I). Patients' knee defects were
      investigated by arthroscopy, and a cartilage biopsy was taken for culturing.
      Patients were randomised, on a single-blind basis, to treatment at the dose
      levels 3-7 (low), 10-30 (medium) or 40-70 (high) spheroids per square centimetre.
      Assessment (adverse events, vital signs, electrocardiography, physical
      examination, concomitant medication and laboratory values) took place 1.5, 3, 6,
      12, 24 and 36 months after chondrocyte implantation. RESULTS: Seventy-five
      patients were included and 73 treated. The incidence of adverse events, of
      patients with adverse events and of patients with treatment-related adverse
      events showed no relevant difference between the treatment groups. There were no
      fatal adverse events, no adverse events led to premature withdrawal from the
      trial and none led to permanent sequelae. Two patients experienced serious
      adverse events considered related to the study treatment: arthralgia 2-3 years
      after implantation and chondropathy 1 and 2 years after implantation.
      CONCLUSIONS: The treatment with chondrosphere(r) was generally well tolerated. No
      relationship was detected between any safety criteria and the dose level:
      Differences between the dose groups in the incidence of any adverse events, and
      in numbers of patients with treatment-related adverse events, were insubstantial.
      TRIAL REGISTRATION: clinicaltrials.gov, NCT01225575 .

PMID- 28499392
TI  - Experimental tumor growth of canine osteosarcoma cell line on chick embryo
      chorioallantoic membrane (in vivo studies).
AB  - The chick embryo chorioallantoic membrane (CAM) model is extensively used in
      human medicine in preclinical oncological studies. The CAM model has several
      advantages: low cost, simple experimental approach, time saving and following "3R
      principles". Research has shown that the human osteosarcoma cell lines U2OS, MMNG
      HOS, and SAOS can form tumors on the CAM. In veterinary medicine, this has been
      described only for feline fibrosarcomas, feline mammary carcinomas and canine
      osteosarcomas. However, in case of canine osteosarcomas, it has been shown that
      only non-adherent osteosarcoma stem cells isolated from KTOSA5 and CSKOS cell
      lines have the ability to form microtumors on the CAM after an incubation period
      of 5 days, in contrast to adherent KTOSA5 and CSKOS cells. In the presented
      study, we have proven that the commercial adherent canine osteosarcoma cell line
      (D-17) can form vascularized tumors on the CAM after the incubation period of 10
      days.

PMID- 28499393
TI  - Reversing the pipeline? Implementing public health evidence-based guidance in
      english local government.
AB  - BACKGROUND: In the UK, responsibility for many public health functions was
      transferred in 2013 from the National Health Service (NHS) to local government; a
      very different political context and one without the NHS history of policy and
      practice being informed by evidence-based guidelines. A problem this move
      presented was whether evidence-based guidelines would be seen as relevant, useful
      and implementable within local government. This study investigates three aspects
      of implementing national evidence-based recommendations for public health within
      a local government context: influences on implementation, how useful guidelines
      are perceived to be and whether the linear evidence-guidelines-practice model is
      considered relevant. METHODS: Thirty-one councillors, public health directors and
      deputy directors and officers and other local government employees were
      interviewed about their experiences implementing evidence-based guidelines.
      Interviews were informed and analysed using a theoretical model of behaviour (COM
      B; Capability, Opportunity, Motivation-Behaviour). RESULTS: Contextual issues
      such as budget, capacity and political influence were important influences on
      implementation. Guidelines were perceived to be of limited use, with concerns
      expressed about recommendations being presented in the abstract, lacking
      specificity and not addressing the complexity of situations or local variations.
      Local evidence was seen as the best starting point, rather than evidence-based
      guidance produced by the traditional linear 'evidence-guidelines-practice' model.
      Local evidence was used to not only provide context for recommendations but also
      replace recommendations when they conflicted with local evidence. CONCLUSIONS:
      Local government users do not necessarily consider national guidelines to be fit
      for purpose at local level, with the consequence that local evidence tends to
      trump evidence-based guidelines. There is thus a tension between the traditional
      model of guideline development and the needs of public health decision-makers and
      practitioners working in local government. This tension needs to be addressed to
      facilitate implementation. One way this might be achieved, and participants
      supported this approach, would be to reverse or re-engineer the traditional
      pipeline of guideline development by starting with local need and examples of
      effective local practice rather than starting with evidence of effectiveness
      synthesised from the international scientific literature. Alternatively, and
      perhaps in addition, training about the relevance of research evidence should
      become a routine for local government staff and councillors.

PMID- 28499394
TI  - SAR1a promoter polymorphisms are not associated with fetal hemoglobin in patients
      with sickle cell disease from Cameroon.
AB  - BACKGROUND: Reactivation of adult hemoglobin (HbF) is currently a dominant
      therapeutic approach to sickle cell disease (SCD). In this study, we have
      investigated among SCD patients from Cameroon, the association of HbF level and
      variants in the HU-inducible small guanosine triphosphate-binding protein,
      secretion-associated and RAS-related (SAR1a) protein, previously shown to be
      associated with HbF after HU treatment in African American SCD patients. RESULTS:
      Only patients >5 years old were included; hemoglobin electrophoresis and a full
      blood count were conducted upon arrival at the hospital. RFLP-PCR was used to
      describe the HBB gene haplotypes and Gap PCR to investigate the 3.7 kb alpha
      globin gene deletion. The iPLEX Gold Sequenom Mass Genotyping Array and cycle
      sequencing were used for the genotyping of four selected SNPs in SAR1a
      (rs2310991; rs4282891; rs76901216 and rs76901220). Genetic analysis was performed
      using an additive genetic model, under a generalized linear regression framework.
      484 patients were studied. No associations were observed between any of the
      promoter variants and baseline HbF, clinical events or other hematological
      indices. CONCLUSION: The results of this study could be explained by possible
      population-specificity of some tagging genomic variants associated with HbF
      production and illustrated the complexity of replicating HbF-promoting variants
      association results across African populations.

PMID- 28499395
TI  - Time course of blood lactate levels, inflammation, and mitochondrial function in
      experimental sepsis.
AB  - BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours
      of resuscitation in sepsis is associated with better outcomes, but the mechanisms
      are unclear. Our objective was to investigate the relationship between the time
      course of Lac, inflammatory response, and mitochondrial respiration during
      experimental sepsis. METHODS: Original data from two previously published studies
      were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h
      starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n =
      8 each). Animals were categorized according to the decrease in Lac during the
      first 6 h of resuscitation (early if >=10% [Lac >=10%] or late if <10% or
      increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and
      mitochondrial function were compared between groups. In a second group of animals
      with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal
      regional Lac exchange was measured, and animals were categorized according to the
      decrease in Lac as in cohort 1. RESULTS: Overall mortality was 20% (4 of 20) in
      the Lac >=10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In
      cohort 1, systemic hemodynamics were similar in the Lac >=10% (n = 13) and Lac
      <10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated
      sepsis and decreased during resusciation in both groups, but they were lower at
      study end in the Lac >=10% group (p = 0.047). Complexes I and II maximal (state
      3) and resting (state 4) isolated brain mitochondrial respiration at study end
      was higher in the Lac >=10% group than in the Lac <10% group, whereas hepatic,
      myocardial, and skeletal muscle mitochondrial respiration was similar in both
      groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end
      was higher in the Lac >=10% group (n = 7) than in the Lac <10% group (n = 9),
      despite similar cardiac output. Hepatic lactate influx and uptake in the Lac
      >=10% group were approximately 1.5 and 3 times higher, respectively, than in the
      Lac <10% group (p = 0.066 for both). CONCLUSIONS: A decrease in Lac >10% during
      early resuscitation (6 h) after abdominal sepsis is associated with lower levels
      of plasma interleukin-6 and improved brain but not hepatic or muscle
      mitochondrial respiration. Blood flow redistribution to abdominal organs in
      animals with early decrease in Lac concentrations increases the potential to both
      deliver and extract Lac.

PMID- 28499396
TI  - Averaging rotational landmarks during total knee arthroplasty reduces component
      malrotation caused by femoral asymmetry.
AB  - BACKGROUND: Femoral component malrotation is a common cause of patient
      dissatisfaction after total knee arthroplasty. The sulcus line (SL) is more
      accurate than Whiteside's line as it corrects for variation in the coronal
      orientation of the groove. The hypothesis is that averaging the SL and posterior
      condylar axis (PCA) will reduce femoral malrotation. METHODS: The component was
      inserted at a position between the SL and PCA in 91 patients. An intraoperative
      photograph was taken showing the landmarks. These were compared to the component
      position achieved relative to the surgical epicondylar axis (SEA) on a
      postoperative CT scan. The component position was compared to the position
      achieved using the individual landmarks. RESULTS: Relative to the SEA, the final
      component position was 0.6 degrees  (SD 1.4 degrees , range -3.8 degrees  to +4.0
      degrees ), the coronally corrected SL position was -0.7 degrees  (SD 2.3 degrees
      , -5.5 degrees  to +4.6 degrees ), the PCA position was 0.9 degrees  (SD 1.9
      degrees , -6.1 degrees  to +5.0 degrees ). Averaging the landmarks significantly
      decreased the variance of the component position compared to using the SL and PCA
      individually. The number of outliers (>3 degrees  from SEA) was also
      significantly less (p < 0.05) for the average position (2/84) when each was
      compared to the SL (16/84) and PCA (14/84) individually. In 21/84 (25%) of cases,
      there was more than 4 degrees  of divergence between the SL and PCA. CONCLUSIONS:
      Averaging the SL and the PCA decreases femoral component malrotation. Femora are
      frequently asymmetrical in the axial plane. Referencing posterior condyles alone
      to set rotation is likely to cause high rates of patellofemoral malalignment.

PMID- 28499398
TI  - Biomechanical evaluation of a novel dualplate fixation method for proximal
      humeral fractures without medial support.
AB  - BACKGROUND: Comminuted fractures of the proximal humerus are generally treated
      with the locking plate system, and clinical results are satisfactory. However,
      unstable support of the medial column results in varus malunion and screw
      perforation. We designed a novel medial anatomical locking plate (MLP) to
      directly support the medial column. Theoretically, the combined application of
      locking plate and MLP (LPMP) would directly provide strong dual-column stability.
      We hypothesized that the LPMP could provide greater construct stability than the
      locking plate alone (LP), locking plate combined with a fibular graft (LPSG), and
      locking plate combined with a distal radius plate (LPDP). METHODS: LP, LPMP,
      LPSG, and LPDP implants were instrumented into the finite element model of a
      proximal humeral fracture. Axial, shear, and rotational loads were applied to the
      models under normal and osteoporotic bone conditions. The whole simulation was
      repeated five times for each fixator. To assess the biomechanical
      characteristics, the construct stiffness, fracture micromotion, stress
      distribution, and neck-shaft angle (NSA) were compared. RESULTS: The LPMP group
      showed significantly greater integral and regional construct stiffness, and
      endured less von Mises stresses, than the other three fixation methods. The
      stresses on the lateral locking plate were dispersed by the MLP. The LPMP group
      showed the least change in NSA. CONCLUSIONS: From the finite element viewpoint,
      the LPMP method provided both lateral and medial direct support. The LPMP system
      was effective in treating proximal humeral fracture with an unstable medial
      column.

PMID- 28499397
TI  - Neutral Lipid Storage Diseases: clinical/genetic features and natural history in
      a large cohort of Italian patients.
AB  - BACKGROUND: A small number of patients affected by Neutral Lipid Storage Diseases
      (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been
      described in various ethnic groups worldwide. However, relatively little is known
      about the progression and phenotypic variability of the disease in large specific
      populations. The aim of our study was to assess the natural history, disability
      and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one
      patients who satisfied the criteria for NLSDs were enrolled in a retrospective
      cross-sectional study to evaluate the genetic aspects, clinical signs at onset,
      disability progression and comorbidities associated with this group of diseases.
      RESULTS: During the clinical follow-up (range: 2-44 years, median: 17.8 years),
      two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five
      (24%) lost their ability to walk or needed help when walking after a mean period
      of 30.6 years of disease. None of the patients required mechanical ventilation.
      No patient required a heart transplant, one patient with NLSD-M was implanted
      with a cardioverter defibrillator for severe arrhythmias. CONCLUSION: The
      genotype/phenotype correlation analysis in our population showed that the same
      gene mutations were associated with a varying clinical onset and course. This
      study highlights peculiar aspects of Italian NLSD patients that differ from those
      observed in Japanese patients, who were found to be affected by a marked
      hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same
      mutations, it is conceivable that some additional genetic or epigenetic factors
      affect the symptoms and progression in this group of diseases.

PMID- 28499399
TI  - Identification of potential Campylobacter jejuni genes involved in biofilm
      formation by EZ-Tn5 Transposome mutagenesis.
AB  - BACKGROUND: Biofilm formation has been suggested to play a role in the survival
      of Campylobacter jejuni in the environment and contribute to the high incidence
      of human campylobacteriosis. Molecular studies of biofilm formation by
      Campylobacter are sparse. RESULTS: We attempted to identify genes that may be
      involved in biofilm formation in seven C. jejuni strains through construction of
      mutants using the EZ-Tn5 Transposome system. Only 14 mutants with reduced biofilm
      formation were obtained, all from one strain of C. jejuni. Three different genes
      of interest, namely CmeB (synthesis of multidrug efflux system transporter
      proteins), NusG (transcription termination and anti-termination protein) and a
      putative transmembrane protein (involved in membrane protein function) were
      identified. The efficiency of the EZ::TN5 transposon mutagenesis approach was
      strain dependent and was unable to generate any mutants from most of the strains
      used. CONCLUSIONS: A diverse range of genes may be involved in biofilm formation
      by C. jejuni. The application of the EZ::TN5 system for construction of mutants
      in different Campylobacter strains is limited.

PMID- 28499400
TI  - EpiTEome: Simultaneous detection of transposable element insertion sites and
      their DNA methylation levels.
AB  - The genome-wide investigation of DNA methylation levels has been limited to
      reference transposable element positions. The methylation analysis of non
      reference and mobile transposable elements has only recently been performed, but
      required both genome resequencing and MethylC-seq datasets. We have created
      epiTEome, a program that detects both new transposable element insertion sites
      and their methylation states from a single MethylC-seq dataset. EpiTEome
      outperforms other split-read insertion site detection programs, even while
      functioning on bisulfite-converted reads. EpiTEome characterizes the previously
      discarded fraction of DNA methylation at sites of new insertions, enabling future
      investigation into the epigenetic regulation of non-reference and transposed
      elements.

PMID- 28499401
TI  - Are general and strategic measures of organizational context and leadership
      associated with knowledge and attitudes toward evidence-based practices in public
      behavioral health settings? A cross-sectional observational study.
AB  - BACKGROUND: Examining the role of modifiable barriers and facilitators is a
      necessary step toward developing effective implementation strategies. This study
      examines whether both general (organizational culture, organizational climate,
      and transformational leadership) and strategic (implementation climate and
      implementation leadership) organizational-level factors predict therapist-level
      determinants of implementation (knowledge of and attitudes toward evidence-based
      practices). METHODS: Within the context of a system-wide effort to increase the
      use of evidence-based practices (EBPs) and recovery-oriented care, we conducted
      an observational, cross-sectional study of 19 child-serving agencies in the City
      of Philadelphia, including 23 sites, 130 therapists, 36 supervisors, and 22
      executive administrators. Organizational variables included characteristics such
      as EBP initiative participation, program size, and proportion of independent
      contractor therapists; general factors such as organizational culture and climate
      (Organizational Social Context Measurement System) and transformational
      leadership (Multifactor Leadership Questionnaire); and strategic factors such as
      implementation climate (Implementation Climate Scale) and implementation
      leadership (Implementation Leadership Scale). Therapist-level variables included
      demographics, attitudes toward EBPs (Evidence-Based Practice Attitudes Scale),
      and knowledge of EBPs (Knowledge of Evidence-Based Services Questionnaire). We
      used linear mixed-effects regression models to estimate the associations between
      the predictor (organizational characteristics, general and strategic factors) and
      dependent (knowledge of and attitudes toward EBPs) variables. RESULTS: Several
      variables were associated with therapists' knowledge of EBPs. Clinicians in
      organizations with more proficient cultures or higher levels of transformational
      leadership (idealized influence) had greater knowledge of EBPs; conversely,
      clinicians in organizations with more resistant cultures, more functional
      organizational climates, and implementation climates characterized by higher
      levels of financial reward for EBPs had less knowledge of EBPs. A number of
      organizational factors were associated with the therapists' attitudes toward
      EBPs. For example, more engaged organizational cultures, implementation climates
      characterized by higher levels of educational support, and more proactive
      implementation leadership were all associated with more positive attitudes toward
      EBPs. CONCLUSIONS: This study provides evidence for the importance of both
      general and strategic organizational determinants as predictors of knowledge of
      and attitudes toward EBPs. The findings highlight the need for longitudinal and
      mixed-methods studies that examine the influence of organizational factors on
      implementation.

PMID- 28499402
TI  - ERK signaling is required for VEGF-A/VEGFR2-induced differentiation of porcine
      adipose-derived mesenchymal stem cells into endothelial cells.
AB  - BACKGROUND: Cell-based therapy that can rejuvenate the endothelium with
      stimulated adipose-derived mesenchymal stem cells (AMSCs) is a promising
      therapeutic strategy for the re-endothelialization of denuded arteries at the
      stenting site. Previously, we have shown that silencing of MMP-2 and MMP-14
      inhibits vascular endothelial growth factor receptor type 2 (VEGFR2) cleavage,
      and induces differentiation of AMSCs toward the endothelial cell (EC) lineage. In
      this study, we examined the underlying signaling pathways that regulate
      differentiation of AMSCs to ECs in vitro through VEGFR2. METHODS: AMSCs were
      isolated from porcine abdominal adipose tissue. The isolated AMSCs were
      characterized by positive expression of CD29, CD44, and CD90 and negative
      expression of CD11b and CD45. The isolated MSCs were transfected with siRNA to
      silence MMP-2, MMP-14, and angiotensin receptor 2 (ATR2). Cells were suspended
      either in endothelial basal media (EBM) or endothelial growth media (EGM) with
      various treatments. Flow cytometry was performed to examine the expression of EC
      markers, and western blot analysis was performed to examine the expression and
      activity of various kinases. Scratch assay was performed to examine the cell
      migration. Data were analyzed by ANOVA using PRISM GraphPad. RESULTS: After 10
      days of stimulation for EC differentiation, the morphology of AMSCs changed to a
      morphology similar to that of ECs. Silencing MMP-2 and MMP-14 resulted in
      significant decrease in the number of migrated cells compared with the EGM-only
      group. ATR2 siRNA transfection did not affect the migration and differentiation
      of AMSCs to ECs. Stimulation of AMSCs for EC differentiation with or without MMP
      2 or MMP-14 siRNA resulted in significant increase in p-ERK, and significant
      decrease in p-JNK. There was no significant change in p-p38 in all three groups
      compared with the EBM group. ERK inhibition resulted in significant decrease in
      the expression of EC markers in the EGM, EGM + MMP-2 siRNA, and EGM + MMP-14
      siRNA groups. The VEGFR2 kinase inhibitor induced a dose-dependent inhibition of
      ERK. CONCLUSION: The ERK signaling pathway is critical for VEGF-A/VEGFR2-induced
      differentiation of AMSCs into ECs. These findings provide new insights into the
      role of the ERK signaling pathway in AMSC differentiation to ECs for potential
      clinical use in cardiovascular diseases.

PMID- 28499403
TI  - Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine
      efficacy by facilitating viral complement escape and mammalian cell transduction.
AB  - Baculovirus-mediated gene transfer has been developed as a vaccine design
      strategy against a number of diseases without apparent viral replication.
      However, it has been hampered by complement-dependent inactivation, thus
      hindering the in vivo application of baculovirus. A variety of approaches have
      been exploited to bypass the complement system in the serum. In this study, we
      constructed and screened a series of baculovirus vectors displaying complement
      interfering factors, of which a baculovirus vector displaying swine IgG1 Fc (pFc)
      showed the highest complement antagonism (75.6%). Flow cytometry analysis of
      transduced cells demonstrated that the baculovirus display of pFc had a
      significant increase in transduction efficiency and transgene expression of
      reporter genes. On this basis, a VSV-G-pseudotyped with swine IgG1 Fc surface
      displayed baculovirus vector was developed to express the classical swine fever
      virus (CSFV) E2 gene. The translational enhancers Syn21 and P10UTR were
      incorporated to improve the antigen expression. The E2 gene was efficiently
      expressed in both insect and mammalian cells. Pigs immunized with this
      recombinant baculovirus developed high levels of E2-specific antibody, CSFV
      specific neutralizing antibody and IFN-gamma-secreting cellular immune responses.
      These results demonstrate that the strategy of surface-displaying swine IgG1 Fc
      has a great potential to improve the efficiency of baculovirus-vectored vaccine
      for CSFV and other swine pathogens.

PMID- 28499404
TI  - Anterograde monosynaptic transneuronal tracers derived from herpes simplex virus
      1 strain H129.
AB  - BACKGROUND: Herpes simplex virus type 1 strain 129 (H129) has represented a
      promising anterograde neuronal circuit tracing tool, which complements the
      existing retrograde tracers. However, the current H129 derived tracers are
      multisynaptic, neither bright enough to label the details of neurons nor capable
      of determining direct projection targets as monosynaptic tracer. METHODS: Based
      on the bacterial artificial chromosome of H129, we have generated a serial of
      recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was
      obtained by inserting binary tandemly connected GFP cassettes into the H129
      genome, and H129-DeltaTK-tdT was obtained by deleting the thymidine kinase (TK)
      gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral
      tracers were tested in vitro and in vivo for the tracing capacity. RESULTS: H129
      G4 is capable of transmitting through multiple synapses, labeling the neurons by
      green florescent protein, and visualizing the morphological details of the
      labeled neurons. H129-DeltaTK-tdT neither replicates nor spreads in neurons
      alone, but transmits to and labels the postsynaptic neurons with tdTomato in the
      presence of complementary expressed TK from a helper virus. H129-DeltaTK-tdT is
      also capable to map the direct projectome of the specific neuron type in the
      given brain regions in Cre transgenic mice. In the tested brain regions where
      circuits are well known, the H129-DeltaTK-tdT tracing patterns are consistent
      with the previous results. CONCLUSIONS: With the assistance of the helper virus
      complimentarily expressing TK, H129-DeltaTK-tdT replicates in the initially
      infected neuron, transmits anterogradely through one synapse, and labeled the
      postsynaptic neurons with tdTomato. The H129-DeltaTK-tdT anterograde monosynaptic
      tracing system offers a useful tool for mapping the direct output in neuronal
      circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal
      strong enough to display the details of neuron morphology.

PMID- 28499405
TI  - A comparative molecular and 3-dimensional structural investigation into cross
      continental and novel avian Trypanosoma spp. in Australia.
AB  - BACKGROUND: Molecular and structural information on avian Trypanosoma spp.
      throughout Australia is limited despite their intrinsic value in understanding
      trypanosomatid evolution, diversity, and structural biology. In Western Australia
      tissue samples (n = 429) extracted from 93 birds in 25 bird species were screened
      using generic PCR primers to investigate the diversity of Trypanosoma spp. To
      investigate avian trypanosome structural biology the first 3-dimensional
      ultrastructural models of a Trypanosoma spp. (Trypanosoma sp. AAT) isolated from
      a bird (currawong, Strepera spp.) were generated using focussed ion beam milling
      combined with scanning electron microscopy (FIB-SEM). RESULTS: Here, we confirm
      four intercontinental species of avian trypanosomes in native Australian birds,
      and identify a new avian Trypanosoma. Trypanosome infection was identified in 18
      birds from 13 different bird species (19%). A single new genotype was isolated
      and found to be closely related to T. culicavium (Trypanosoma sp. CC2016 B002).
      Other Trypanosoma spp. identified include T. avium, T. culicavium, T.
      thomasbancrofti, Trypanosoma sp. TL.AQ.22, Trypanosoma sp. AAT, and an
      uncharacterised Trypanosoma sp. (group C-III sensu Zidkova et al. (Infect Genet
      Evol 12:102-112, 2012)), all previously identified in Australia or other
      continents. Serially-sectioning Trypanosoma sp. AAT epimastigotes using FIB-SEM
      revealed the disc-shaped kinetoplast pocket attached perpendicular to the
      branching mitochondrion. Additionally, the universal minicircle sequence within
      the kinetoplast DNA and the associated binding protein were determined in
      Trypanosoma sp. AAT. CONCLUSIONS: These results indicate that bird trypanosomes
      are relatively conserved across continents, while being locally diverse, which
      supports the hypothesis that bird trypanosomes exist as fewer species than
      described in the literature. Evidence exists that avian Trypanosoma spp. are
      infecting mammals and could be transmitted by haemadipsid leeches. Trypanosoma
      sp. AAT is most likely a separate species currently found only in Australia and
      the first 3-dimentional ultrastructural analysis of an avian trypanosome provides
      interesting information on their morphology and organelle arrangement.

PMID- 28499406
TI  - Cattle genome-wide analysis reveals genetic signatures in trypanotolerant N'Dama.
AB  - BACKGROUND: Indigenous cattle in Africa have adapted to various local
      environments to acquire superior phenotypes that enhance their survival under
      harsh conditions. While many studies investigated the adaptation of overall
      African cattle, genetic characteristics of each breed have been poorly studied.
      RESULTS: We performed the comparative genome-wide analysis to assess evidence for
      subspeciation within species at the genetic level in trypanotolerant N'Dama
      cattle. We analysed genetic variation patterns in N'Dama from the genomes of 101
      cattle breeds including 48 samples of five indigenous African cattle breeds and
      53 samples of various commercial breeds. Analysis of SNP variances between cattle
      breeds using wMI, XP-CLR, and XP-EHH detected genes containing N'Dama-specific
      genetic variants and their potential associations. Functional annotation analysis
      revealed that these genes are associated with ossification, neurological and
      immune system. Particularly, the genes involved in bone formation indicate that
      local adaptation of N'Dama may engage in skeletal growth as well as immune
      systems. CONCLUSIONS: Our results imply that N'Dama might have acquired distinct
      genotypes associated with growth and regulation of regional diseases including
      trypanosomiasis. Moreover, this study offers significant insights into
      identifying genetic signatures for natural and artificial selection of diverse
      African cattle breeds.

PMID- 28499407
TI  - Early neurosyphilis presenting with facial palsy and an oral ulcer in a patient
      who is human immunodeficiency virus positive: a case report.
AB  - BACKGROUND: Neurosyphilis is the tertiary stage of Treponema pallidum infection
      that involves the central nervous system, which occurs within days or weeks after
      an initial syphilis infection, especially in immunocompromised patients. The
      diagnosis of neurosyphilis is quite challenging as it is uncommon and often
      presents with obscure symptoms since any organ system may be involved. CASE
      PRESENTATION: We describe a case of a 40-year-old African man who is human
      immunodeficiency virus positive with early neurosyphilis who presented with a
      stiff neck, headache, confusion, restlessness, and a left-sided chest pain; he
      did not respond to an empiric treatment of ceftriaxone and fluconazole for
      meningitis, and tramadol for headache. Ten days after admission, he developed
      generalized tonic-clonic convulsions; on examination he had ipsilateral facial
      nerve palsy and an oral ulcer, and responded well to benzathine penicillin
      treatment. CONCLUSIONS: Laboratory diagnosis of neurosyphilis is challenging
      because to date there is no single laboratory test which is considered sensitive
      enough for diagnosis of the disease, especially in resource-limited settings.
      Clinical judgment is still an important part of diagnosis; and neurosyphilis
      should be considered a diagnostic differential in patients with Human
      Immunodeficiency Virus presenting with central nervous system involvement and in
      other high-risk patients.

PMID- 28499409
TI  - In your face: the biased judgement of fear-anger expressions in violent
      offenders.
AB  - BACKGROUND: Why is it that certain violent criminals repeatedly find themselves
      engaged in brawls? Many inmates report having felt provoked or threatened by
      their victims, which might be due to a tendency to ascribe malicious intentions
      when faced with ambiguous social signals, termed hostile attribution bias.
      METHODS: The present study presented morphed fear-anger faces to prison inmates
      with a history of violent crimes, a history of child sexual abuse, and to matched
      controls form the general population. Participants performed a fear-anger
      decision task. Analyses compared both response frequencies and measures derived
      from psychophysical functions fitted to the data. In addition, a test to
      distinguish basic facial expressions and questionnaires for aggression,
      psychopathy and personality disorders were administered. RESULTS: Violent
      offenders present with a reliable hostile attribution bias, in that they rate
      ambiguous fear-anger expressions as more angry, compared to both the control
      population and perpetrators of child sexual abuse. Psychometric functions show a
      lowered threshold to detect anger in violent offenders compared to the general
      population. This effect is especially pronounced for male faces, correlates with
      self-reported aggression and presents in absence of a general emotion recognition
      impairment. CONCLUSIONS: The results indicate that a hostile attribution, related
      to individual level of aggression and pronounced for male faces, might be one
      mechanism mediating physical violence.

PMID- 28499408
TI  - Organizational theory for dissemination and implementation research.
AB  - BACKGROUND: Even under optimal internal organizational conditions, implementation
      can be undermined by changes in organizations' external environments, such as
      fluctuations in funding, adjustments in contracting practices, new technology,
      new legislation, changes in clinical practice guidelines and recommendations, or
      other environmental shifts. Internal organizational conditions are increasingly
      reflected in implementation frameworks, but nuanced explanations of how
      organizations' external environments influence implementation success are lacking
      in implementation research. Organizational theories offer implementation
      researchers a host of existing, highly relevant, and heretofore largely untapped
      explanations of the complex interaction between organizations and their
      environment. In this paper, we demonstrate the utility of organizational theories
      for implementation research. DISCUSSION: We applied four well-known
      organizational theories (institutional theory, transaction cost economics,
      contingency theories, and resource dependency theory) to published descriptions
      of efforts to implement SafeCare, an evidence-based practice for preventing child
      abuse and neglect. Transaction cost economics theory explained how frequent,
      uncertain processes for contracting for SafeCare may have generated
      inefficiencies and thus compromised implementation among private child welfare
      organizations. Institutional theory explained how child welfare systems may have
      been motivated to implement SafeCare because doing so aligned with expectations
      of key stakeholders within child welfare systems' professional communities.
      Contingency theories explained how efforts such as interagency collaborative
      teams promoted SafeCare implementation by facilitating adaptation to child
      welfare agencies' internal and external contexts. Resource dependency theory
      (RDT) explained how interagency relationships, supported by contracts, memoranda
      of understanding, and negotiations, facilitated SafeCare implementation by
      balancing autonomy and dependence on funding agencies and SafeCare developers. In
      addition to the retrospective application of organizational theories demonstrated
      above, we advocate for the proactive use of organizational theories to design
      implementation research. For example, implementation strategies should be
      selected to minimize transaction costs, promote and maintain congruence between
      organizations' dynamic internal and external contexts over time, and
      simultaneously attend to organizations' financial needs while preserving their
      autonomy. We describe implications of applying organizational theory in
      implementation research for implementation strategies, the evaluation of
      implementation efforts, measurement, research design, theory, and practice. We
      also offer guidance to implementation researchers for applying organizational
      theory.

PMID- 28499410
TI  - Comparison of the acute ocular manifestations of Stevens-Johnson syndrome and
      toxic epidermal necrolysis in Chinese eyes: a 15-year retrospective study.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are rare but life-threatening conditions that initially affect the skin and
      mucous membranes. The aim of this study was to compare the acute ocular
      manifestations between SJS and TEN. METHODS: The initial presenting ophthalmic
      records of patients with either SJS (<30% body surface area involvement) or TEN
      (> = 30% involvement), who were treated at one tertiary burn center in Hong Kong
      between 1999 and 2014, were retrospectively analyzed and compared. RESULTS: A
      total of 20 SJS and 12 TEN cases were included. All were drug-induced. The
      patient demographics and treatment received were comparable. Overall, 40% of SJS
      and 75% of TEN patients had acute ocular surface inflammation. When comparing the
      two groups, there was a significant difference in the number of cases with mild
      involvement (5% in SJS, 42% in TEN, p = 0.01), while no statistically significant
      differences were found (p > 0.05) comparing between the moderate (15% in SJS, 0%
      in TEN) and severe groups (20% in SJS, 33% in TEN). CONCLUSIONS: Ocular surface
      inflammation was common during the acute phase in both SJS and TEN. TEN had a
      significantly higher number of cases with mild ocular involvement when compared
      with SJS, but no significant difference between the number of moderate and severe
      cases between the two groups.

PMID- 28499411
TI  - Paraneoplastic acral vascular syndrome in a patient with metastatic melanoma
      under immune checkpoint blockade.
AB  - BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon
      which is observed in patients with adenocarcinomas and other malignancies.
      Various potential pathogenic mechanisms such as tumour invasion of sympathetic
      nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted
      substances, and immunological mechanisms have been suggested. CASE PRESENTATION:
      We report a 60-year-old Caucasian male attended our hospital with a bulky lymph
      node mass in the right axilla. Extirpation of a lymph node conglomerate revealed
      5 melanoma lymph node metastases. Computed tomography showed a liver metastasis
      (diameter: 3.8 cm), several retroperitoneal metastases, bilateral metastases in
      the lung hilus, and prepectoral subcutaneous metastases (Stage IV; pTx, N3, M1c).
      Lactate dehydrogenase and S100B were slightly elevated. Combination therapy of
      nivolumab (1 mg/kg BW) and ipilimumab (3 mg/kg BW) was started. Three weeks after
      the first combination therapy he developed progressive erythema, paraesthesia and
      pain on the fingertips of both hands. Both cold and warmth was not well tolerated
      by the patient. Complete work-up excluded associated conditions or factors such
      as haematological disorders, rheumatologic disorders, hypertension, diabetes or
      smoking. Treatment was initiated with prostacyclin 20 MUg twice daily and oral
      prednisolone 50 mg in tapering dosage. However, prostacyclin was stopped after
      the first applications because the pain increased during infusion. The second
      course of nivolumab and ipilimumab was administered. About 2 weeks later, the
      patient presented with increased pain and small subungual necrosis. We treated
      the patient with oral analgetics and intravenous prednisolone 500 mg in tapering
      dosage. On digital substraction angiography occlusion of all arteries of the
      fingers was demonstrated. Further rheologic and anti-melanoma treatments were
      refused by the patient. About 2 months after the second course of nivolumab and
      ipilimumab combination therapy several fingers showed severe gangrene which
      finally led to amputations of end phalanges of several fingers. Histopathology
      did not reveal evidence for vasculitis or other primary vascular pathologies.
      During the following 2 months the patient experienced dramatic progress of his
      metastatic disease and finally died at multi-organ failure. CONCLUSION: Presence
      of rapidly progressive digital ischemia in an elderly patient with cancer should
      always raise clinical suspicion of a paraneoplastic phenomenon when other
      possible causes have been excluded. In patients treated with immune checkpoint
      inhibitors such as CTLA-4 and PD-L1 blockers PVAS-like events have not been
      reported so far. However, it is debatable whether immune checkpoint blockade may
      play a pathogenetic role in the development of PAVS in patients with
      malignancies.

PMID- 28499412
TI  - Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG
      promoter regions in lymphoblastoid cell lines.
AB  - BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the
      molecular mechanisms through which genetic and environmental factors contribute
      to the risk of multifactorial diseases. There are two types of commonly used DNA
      bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid
      cell lines (LCLs), which are available for genetic epidemiological studies.
      Therefore, to extend our knowledge of the difference in DNA methylation status
      between LCLs and PBCs is important in human population studies that use these DNA
      sources to elucidate the epigenetic risks for multifactorial diseases. We
      analyzed the methylation status of the autosomes for 192 and 92 DNA samples that
      were obtained from PBCs and LCLs, respectively, using a human methylation 450 K
      array. After excluding SNP-associated methylation sites and low-call sites,
      400,240 sites were subjected to analysis using a generalized linear model with
      cell type, sex, and age as the independent variables. RESULTS: We found that the
      large proportion of sites showed lower methylation levels in LCLs compared with
      PBCs, which is consistent with previous reports. We also found that significantly
      different methylation sites tend to be located on the outside of the CpG island
      and in a region relatively far from the transcription start site. Additionally,
      we observed that the methylation change of the sites in the low-CpG promoter
      region was remarkable. Finally, it was shown that the correlation between the
      chronological age and ageing-associated methylation sites in ELOVL2 and FHL2 in
      the LCLs was weaker than that in the PBCs. CONCLUSIONS: The methylation levels of
      highly methylated sites of the low-CpG-density promoters in PBCs decreased in the
      LCLs, suggesting that the methylation sites located in low-CpG-density promoters
      could be sensitive to demethylation in LCLs. Despite being generated from a
      single cell type, LCLs may not always be a proxy for DNA from PBCs in studies of
      epigenome-wide analysis attempting to elucidate the role of epigenetic change in
      disease risks.

PMID- 28499413
TI  - Ranking metrics in gene set enrichment analysis: do they matter?
AB  - BACKGROUND: There exist many methods for describing the complex relation between
      changes of gene expression in molecular pathways or gene ontologies under
      different experimental conditions. Among them, Gene Set Enrichment Analysis seems
      to be one of the most commonly used (over 10,000 citations). An important
      parameter, which could affect the final result, is the choice of a metric for the
      ranking of genes. Applying a default ranking metric may lead to poor results.
      METHODS AND RESULTS: In this work 28 benchmark data sets were used to evaluate
      the sensitivity and false positive rate of gene set analysis for 16 different
      ranking metrics including new proposals. Furthermore, the robustness of the
      chosen methods to sample size was tested. Using k-means clustering algorithm a
      group of four metrics with the highest performance in terms of overall
      sensitivity, overall false positive rate and computational load was established
      i.e. absolute value of Moderated Welch Test statistic, Minimum Significant
      Difference, absolute value of Signal-To-Noise ratio and Baumgartner-Weiss
      Schindler test statistic. In case of false positive rate estimation, all selected
      ranking metrics were robust with respect to sample size. In case of sensitivity,
      the absolute value of Moderated Welch Test statistic and absolute value of Signal
      To-Noise ratio gave stable results, while Baumgartner-Weiss-Schindler and Minimum
      Significant Difference showed better results for larger sample size. Finally, the
      Gene Set Enrichment Analysis method with all tested ranking metrics was
      parallelised and implemented in MATLAB, and is available at
      https://github.com/ZAEDPolSl/MrGSEA . CONCLUSIONS: Choosing a ranking metric in
      Gene Set Enrichment Analysis has critical impact on results of pathway enrichment
      analysis. The absolute value of Moderated Welch Test has the best overall
      sensitivity and Minimum Significant Difference has the best overall specificity
      of gene set analysis. When the number of non-normally distributed genes is high,
      using Baumgartner-Weiss-Schindler test statistic gives better outcomes. Also, it
      finds more enriched pathways than other tested metrics, which may induce new
      biological discoveries.

PMID- 28499414
TI  - HLAscan: genotyping of the HLA region using next-generation sequencing data.
AB  - BACKGROUND: Several recent studies showed that next-generation sequencing (NGS)
      based human leukocyte antigen (HLA) typing is a feasible and promising technique
      for variant calling of highly polymorphic regions. To date, however, no method
      with sufficient read depth has completely solved the allele phasing issue. In
      this study, we developed a new method (HLAscan) for HLA genotyping using NGS
      data. RESULTS: HLAscan performs alignment of reads to HLA sequences from the
      international ImMunoGeneTics project/human leukocyte antigen (IMGT/HLA) database.
      The distribution of aligned reads was used to calculate a score function to
      determine correctly phased alleles by progressively removing false-positive
      alleles. Comparative HLA typing tests using public datasets from the 1000 Genomes
      Project and the International HapMap Project demonstrated that HLAscan could
      perform HLA typing more accurately than previously reported NGS-based methods
      such as HLAreporter and PHLAT. In addition, the results of HLA-A, -B, and -DRB1
      typing by HLAscan using data generated by NextGen were identical to those
      obtained using a Sanger sequencing-based method. We also applied HLAscan to a
      family dataset with various coverage depths generated on the Illumina HiSeq X-TEN
      platform. HLAscan identified allele types of HLA-A, -B, -C, -DQB1, and -DRB1 with
      100% accuracy for sequences at >= 90* depth, and the overall accuracy was 96.9%.
      CONCLUSIONS: HLAscan, an alignment-based program that takes read distribution
      into account to determine true allele types, outperformed previously developed
      HLA typing tools. Therefore, HLAscan can be reliably applied for determination of
      HLA type across the whole-genome, exome, and target sequences.

PMID- 28499415
TI  - Discrimination of candidate subgenome-specific loci by linkage map construction
      with an S1 population of octoploid strawberry (Fragaria * ananassa).
AB  - BACKGROUND: The strawberry, Fragaria * ananassa, is an allo-octoploid (2n = 8x =
      56) and outcrossing species. Although it is the most widely consumed berry crop
      in the world, its complex genome structure has hindered its genetic and genomic
      analysis, and thus discrimination of subgenome-specific loci among the
      homoeologous chromosomes is needed. In the present study, we identified candidate
      subgenome-specific single nucleotide polymorphism (SNP) and simple sequence
      repeat (SSR) loci, and constructed a linkage map using an S1 mapping population
      of the cultivar 'Reikou' with an IStraw90 Axiom(r) SNP array and previously
      published SSR markers. RESULTS: The 'Reikou' linkage map consisted of 11,574 loci
      (11,002 SNPs and 572 SSR loci) spanning 2816.5 cM of 31 linkage groups. The
      11,574 loci were located on 4738 unique positions (bin) on the linkage map. Of
      the mapped loci, 8999 (8588 SNPs and 411 SSR loci) showed a 1:2:1 segregation
      ratio of AA:AB:BB allele, which suggested the possibility of deriving loci from
      candidate subgenome-specific sequences. In addition, 2575 loci (2414 SNPs and 161
      SSR loci) showed a 3:1 segregation of AB:BB allele, indicating they were derived
      from homoeologous genomic sequences. Comparative analysis of the homoeologous
      linkage groups revealed differences in genome structure among the subgenomes.
      CONCLUSIONS: Our results suggest that candidate subgenome-specific loci are
      randomly located across the genomes, and that there are small- to large-scale
      structural variations among the subgenomes. The mapped SNPs and SSR loci on the
      linkage map are expected to be seed points for the construction of
      pseudomolecules in the octoploid strawberry.

PMID- 28499416
TI  - Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced
      oxidative damage: a protocol for a systematic review.
AB  - BACKGROUND: Hyperglycaemia-induced oxidative damage is a well-established factor
      implicated in the development of diabetic cardiomyopathy (DCM) in diabetic
      individuals. Some of the well-known characteristics of DCM include increased
      myocardial left ventricular wall thickness and remodelling that result in reduced
      cardiac efficiency. To prevent this, an increasing number of pharmacological
      compounds such as N-acetyl cysteine (NAC) are explored for their antioxidant
      properties. A few studies have shown that NAC can ameliorate hyperglycaemia
      induced oxidative damage within the heart. Hence, the objective of this review is
      to synthesise the available evidence pertaining to the cardioprotective role of
      NAC against hyperglycaemia-induced oxidative damage and thus prevent DCM.
      METHODS: This systematic review protocol will be reported in accordance with the
      Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols
      (PRISMA-P) 2015 statement. We will perform a comprehensive search on major
      databases such as EMBASE, Cochrane Library, PubMed and Google scholar for
      original research articles published from January 1960 to March 2017. We will
      only report on literature that is available in English. Two authors will
      independently screen for eligible studies using pre-defined criteria, and data
      extraction will be done in duplicate. All discrepancies will be resolved by
      consensus or consultation of a third reviewer. The quality of studies will be
      checked using Cochrane Risk of Bias Assessment Tool and The Joanna Briggs
      Institute (JBI) Critical Appraisal tools for non-randomised experimental studies.
      Heterogeneity across studies will be assessed using the Cochrane Q statistic and
      the inconsistency index (I 2). We will use the random effects model to calculate
      a pooled estimate. DISCUSSION: Although several studies have shown that NAC can
      ameliorate hyperglycaemia-induced oxidative damage within the heart, this
      systematic review will be the first pre-registered synthesis of data to identify
      the cardioprotective potential of NAC against hyperglycaemia-induced oxidative
      damage. This result will help guide future research evaluating the
      cardioprotective role of NAC against DCM and better identify possible mechanisms
      of action for NAC to prevent oxidative damage with a diabetic heart. SYSTEMIC
      REVIEW REGISTRATION: PROSPERO CRD42017055851 .

PMID- 28499418
TI  - Early morning urine collection to improve urinary lateral flow LAM assay
      sensitivity in hospitalised patients with HIV-TB co-infection.
AB  - BACKGROUND: Urine LAM testing has been approved by the WHO for use in
      hospitalised patients with advanced immunosuppression. However, sensitivity
      remains suboptimal. We therefore examined the incremental diagnostic sensitivity
      of early morning urine (EMU) versus random urine sampling using the Determine(r)
      lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients.
      METHODS: Consenting HIV-infected inpatients, screened as part of a larger
      prospective randomized controlled trial, that were treated for TB, and could
      donate matched random and EMU samples were included. Thus paired sample were
      collected from the same patient, LF-LAM was graded using the pre-January 2014,
      with grade 1 and 2 manufacturer-designated cut-points (the latter designated
      grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture
      positivity served as the reference standard (definite TB). Those treated for TB
      but not meeting this standard were designated probable TB. RESULTS: 123 HIV
      infected patients commenced anti-TB treatment and provided matched random and EMU
      samples. 33% (41/123) and 67% (82/123) had definite and probable TB,
      respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using
      the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with
      random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF
      LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p =
      0.001). LF-LAM specificity was not determined. CONCLUSION: This proof of concept
      study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised
      TB-HIV co-infected patients. These data have implications for clinical practice.

PMID- 28499417
TI  - Genome-wide characterization and expression analyses of superoxide dismutase
      (SOD) genes in Gossypium hirsutum.
AB  - BACKGROUND: Superoxide dismutases (SODs) are a key antioxidant enzyme family,
      which have been implicated in protecting plants against the toxic effects of
      reactive oxygen species. Despite current studies have shown that the gene family
      are involved in plant growth and developmental processes and biotic and abiotic
      stress responses, little is known about its functional role in upland cotton.
      RESULTS: In the present study, we comprehensively analyzed the characteristics of
      the SOD gene family in upland cotton (Gossypium hirsutum). Based on their
      conserved motifs, 18 GhSOD genes were identified and phylogenetically classified
      into five subgroups which corroborated their classifications based on gene
      structure patterns and subcellular localizations. The GhSOD sequences were
      distributed at different densities across 12 of the 26 chromosomes. The conserved
      domains, gene family evolution cis-acting elements of promoter regions and miRNA
      mediated posttranscriptional regulation were predicted and analyzed. In addition,
      the expression pattern of 18 GhSOD genes were tested in different tissues/organs
      and developmental stages, and different abiotic stresses and abscisic acid, which
      indicated that the SOD gene family possessed temporal and spatial specificity
      expression specificity and may play important roles in reactive oxygen species
      scavenging caused by various stresses in upland cotton. CONCLUSIONS: This study
      describes the first genome-wide analysis of the upland cotton SOD gene family,
      and the results will help establish a foundation for the further cloning and
      functional verification of the GhSOD gene family during stress responses, leading
      to crop improvement.

PMID- 28499419
TI  - Across-proteome modeling of dimer structures for the bottom-up assembly of
      protein-protein interaction networks.
AB  - BACKGROUND: Deciphering complete networks of interactions between proteins is the
      key to comprehend cellular regulatory mechanisms. A significant effort has been
      devoted to expanding the coverage of the proteome-wide interaction space at
      molecular level. Although a growing body of research shows that protein docking
      can, in principle, be used to predict biologically relevant interactions, the
      accuracy of the across-proteome identification of interacting partners and the
      selection of near-native complex structures still need to be improved. RESULTS:
      In this study, we developed a new method to discover and model protein
      interactions employing an exhaustive all-to-all docking strategy. This approach
      integrates molecular modeling, structural bioinformatics, machine learning, and
      functional annotation filters in order to provide interaction data for the bottom
      up assembly of protein interaction networks. Encouragingly, the success rates for
      dimer modeling is 57.5 and 48.7% when experimental and computer-generated monomer
      structures are employed, respectively. Further, our protocol correctly identifies
      81% of protein-protein interactions at the expense of only 19% false positive
      rate. As a proof of concept, 61,913 protein-protein interactions were confidently
      predicted and modeled for the proteome of E. coli. Finally, we validated our
      method against the human immune disease pathway. CONCLUSIONS: Protein docking
      supported by evolutionary restraints and machine learning can be used to reliably
      identify and model biologically relevant protein assemblies at the proteome
      scale. Moreover, the accuracy of the identification of protein-protein
      interactions is improved by considering only those protein pairs co-localized in
      the same cellular compartment and involved in the same biological process. The
      modeling protocol described in this communication can be applied to detect
      protein-protein interactions in other organisms and pathways as well as to
      construct dimer structures and estimate the confidence of protein interactions
      experimentally identified with high-throughput techniques.

PMID- 28499420
TI  - Continuous femoral nerve blockade and single-shot sciatic nerve block promotes
      better analgesia and lower bleeding for total knee arthroplasty compared to
      intrathecal morphine: a randomized trial.
AB  - BACKGROUND: Knee arthroplasty leads to postoperative pain. This study compares
      analgesia and postoperative bleeding achieved by intrathecal morphine with a
      continuous femoral plus single-shot sciatic nerve block. METHODS: A randomized
      non-blinded clinical trial enrolled patients aged over 18 years old, ASA I to III
      who underwent total knee arthroplasty. All patients underwent spinal anesthesia
      with isobaric bupivacaine, 20 mg. One group received 100 mcg of intrathecal
      morphine (M group), and the other received a femoral nerve block by continuous
      infusion plus a "single shot" block of the sciatic nerve at the end of the
      surgery (FI group). Pain score from verbal numeric rating scale (VNRS) and
      morphine consumption during the first 72 h, as well as motor blockade, adverse
      effects, and postoperative bleeding were recorded. Analysis of variance of
      repeated measures with Bonferroni post-test, t-test and Fisher exact test were
      used for statistical analysis. RESULTS: Thirty nine patients completed the study
      (M = 20; FI = 19 patients) and were similar except for higher age in the FI
      group. Motor blockade as well as movement pain during postanesthesia care unit
      (PACU) staying were not different between the groups, but movement pain was
      significantly lower in FI group after 24 h. Postoperative bleeding (ml) was lower
      in FI group. CONCLUSIONS: Continuous femoral nerve block combined with sciatic
      nerve block provides effective for postoperative analgesia in patients undergoing
      total knee arthroplasty, with lower pain scores after 24 h and a lower incidence
      of adverse effects and bleeding compared to intrathecal morphine. TRIAL
      REGISTRATION: Retrospectively registered on https://clinicaltrials.gov/ under
      identifier NCT02882152 , 23rd December, 2016.

PMID- 28499421
TI  - Patterns of use and appropriateness of antibiotics prescribed to patients
      receiving haemodialysis: an observational study.
AB  - BACKGROUND: There are limited published data on the types and appropriateness of
      oral and intravenous (IV) antibiotics prescribed to patients receiving
      haemodialysis. This information is critical to optimise antibiotic prescribing.
      Therefore this study aims to describe the patterns of use and the appropriateness
      of oral and IV antibiotics prescribed to patients receiving haemodialysis.
      METHODS: This was a prospective, observational study across four community and
      two hospital inpatient haemodialysis units in Melbourne, Australia. Data were
      collected from July 2014 to January 2015 from participants. Antibiotic regimens
      prescribed were compared with nationally available antibiotic guidelines and then
      classified as being either appropriate, inappropriate or not assessable by an
      expert multidisciplinary team using the National Antimicrobial Prescribing Survey
      tool. RESULTS: Overall, 114 participants consented to this study where 55.3%
      (63/114) received antibiotics and 235 antibiotic regimens were prescribed at a
      rate of 69.1 antibiotic regimens/100 patient-months. The most common oral
      antibiotics prescribed were amoxycillin/clavulanic acid and cephalexin. The most
      common IV antibiotics prescribed were vancomycin, piperacillin/tazobactam,
      cephazolin and ceftriaxone. The percentage of inappropriate antibiotic regimens
      prescribed were 34.9% (15/43) in the community setting and 22.1% (40/181) in the
      hospital setting. Furthermore, 29.4% (30/102) of oral and 20.5% (25/122) of IV
      antibiotic regimens were inappropriate with incorrect dosing as the primary
      reason. CONCLUSION: Although this study is limited by the sample size, it
      describes the high antibiotic exposure that patients receiving haemodialysis
      experience. Of concern is inappropriate dose and frequency being a major issue.
      This requires interventions focused on the quality use of medicines and
      antimicrobial stewardship aspects of prescribing in this population.

PMID- 28499422
TI  - Identification of novel genes associated with HIV-1 latency by analysis of
      histone modifications.
AB  - BACKGROUND: A reservoir of HIV-1 is a major obstacle in eliminating HIV-1 in
      patients because it can reactivate in stopping antiretroviral therapy (ART).
      Histone modifications, such as acetylation and methylation, play a critical role
      in the organization of chromatin domains and the up- or downregulation of gene
      expression. Although many studies have reported that an epigenetic mechanism is
      strongly involved in the maintenance of HIV-1 transcriptional latency, neither
      the epigenetic control of viral replication nor how HIV-1 latency is maintained
      is not fully understood. RESULTS: We re-analyzed a high throughput parallel DNA
      sequencing (ChIP-seq) data from previous work to investigate the effect of
      histone modifications, H3K4me3 and H3K9ac, on HIV-1 latency in terms of
      chromosome distribution. The outputs of ChIP-seq from uninfected CD4+ T cell
      lines and HIV-1 latently infected cells were aligned to hg18 using bowtie and
      then analyzed using various software packages. Certain chromosomes (16, 17, 19,
      and 22) were significantly enriched for histone modifications in both decreased
      and increased islands. In the same chromosomes in HIV-1 latently infected cells,
      38 decreased and 41 increased islands from common islands of H3K4me3 and H3K9ac
      were selected for functional annotation. In Gene Ontology analysis, the 38 genes
      associated with decreased islands were involved in the regulation of biological
      process, regulation of cellular process, biological regulation, and purinergic
      receptor signaling pathway, while the 41 genes associated with increased islands
      were involved in nucleic acid binding, calcium-activated cation channel activity,
      DNA binding, and zinc ion binding. In Pathway Commons analysis, the 38 genes were
      strongly involved in the p63 transcription factor network, while the 41 genes
      were involved in the RNA polymerase III transcription termination pathway.
      Several genes such as Nuclear factor I X (NFIX) and TNF receptor association
      factor 4 (TRAF4) were selected as candidate genes for HIV latency. Especially,
      NFIX was highly expressed in HIV-1 latently infected cell lines and showed a
      dramatic reduction in expression after phorbol-13-myristate-12-acetate (PMA)
      treatment. CONCLUSIONS: These results show that the unique enrichment of histone
      modifications and its linked genes in specific chromosomes might play a critical
      role in the establishment and maintenance of HIV-1 latency.

PMID- 28499423
TI  - Could cash and good parenting affect child cognitive development? A cross
      sectional study in South Africa and Malawi.
AB  - BACKGROUND: Social protection interventions, including cash grants and care
      provision have been shown to effectively reduce some negative impacts of the HIV
      epidemic on adolescents and families. Less is known about the role of social
      protection on younger HIV affected populations. This study explored the impact of
      cash grants on children's cognitive development. Additionally, we examined
      whether combined cash and care (operationalised as good parenting) was associated
      with improved cognitive outcomes. METHODS: The sample included 854 children, aged
      5 - 15, participating in community-based organisation (CBO) programmes for
      children affected by HIV in South Africa and Malawi. Data on child cognitive
      functioning were gathered by a combination of caregiver report and observer
      administered tests. Primary caregivers also reported on the economic situation of
      the family, cash receipt into the home, child and household HIV status. Parenting
      was measured on a 10 item scale with good parenting defined as a score of 8 or
      above. RESULTS: About half of families received cash (55%, n = 473), only 6% (n =
      51) reported good parenting above the cut-off point but no cash, 18% (n = 151)
      received combined cash support and reported good parenting, and 21% (n = 179) had
      neither. Findings show that cash receipt was associated with enhanced child
      cognitive outcomes in a number of domains including verbal working memory,
      general cognitive functioning, and learning. Furthermore, cash plus good
      parenting provided an additive effect. Child HIV status had a moderating effect
      on the association between cash or/plus good parenting and cognitive outcomes.
      The association between cash and good parenting and child cognitive outcomes
      remained significant among both HIV positive and negative children, but overall
      the HIV negative group benefited more. CONCLUSIONS: This study shows the
      importance of cash transfers and good parenting on cognitive development of young
      children living in HIV affected environments. Our data clearly indicate that
      combined provision (cash plus good parenting) have added value.

PMID- 28499424
TI  - Ultrastructural deposits appearing as "zebra bodies" in renal biopsy: Fabry
      disease?- comparative case reports.
AB  - BACKGROUND: Fabry Disease (FD) is a genetic disorder caused by alpha
      galactosidase A deficiency. Certain drugs, such as hydroxychloroquine, can
      produce renal deposits that mimic morphological findings seen in FD,
      characterizing a type of drug-induced renal phospholipidosis. CASE PRESENTATION:
      Case 1: A 28-year-old female patient with systemic lupus erythematosus who had
      been using hydroxychloroquine for 14 months presented subnephrotic proteinuria.
      Renal biopsy showed deposits compatible with FD. Neither activity analysis of
      alpha-galactosidase A nor genetic analysis were available and were not performed.
      These deposits were not detected in a subsequent renal biopsy three years after
      withdrawal of the medication, characterizing a possible hydroxychloroquine
      induced renal phospholipidosis. Case 2: A 29-year-old male patient presented with
      acroparesthesia, angiokeratomas, cornea verticillata and subnephrotic
      proteinuria. Deposits compatible with FD were detected upon renal biopsy. The
      evaluation of alpha-galactosidase A showed no activity in both blood and
      leukocytes. Genetic analysis identified an M284 T mutation in exon 6, and such
      mutation was also found in other family members. CONCLUSION: Clinical
      investigation is necessary in suspected cases of Fabry Disease upon renal biopsy
      in order to confirm diagnosis. Drug-induced renal phospholipidosis should be
      considered in differential diagnosis in cases with intracellular osmiophilic,
      lamellar inclusions in electron microscopy.

PMID- 28499426
TI  - Erratum to: Oral intake of a combination of glucosyl hesperidin and caffeine
      elicits an antiobesity effect in healthy, moderately obese subjects: a randomized
      double-blind placebo-controlled trial.

PMID- 28499425
TI  - Hand-held cell phone use while driving legislation and observed driver behavior
      among population sub-groups in the United States.
AB  - BACKGROUND: Cell phone use behaviors are known to vary across demographic sub
      groups and geographic locations. This study examined whether universal hand-held
      calling while driving bans were associated with lower road-side observed hand
      held cell phone conversations across drivers of different ages (16-24, 25-59,
      >=60 years), sexes, races (White, African American, or other), ruralities
      (suburban, rural, or urban), and regions (Northeast, Midwest, South, and West).
      METHODS: Data from the 2008-2013 National Occupant Protection Use Survey were
      merged with states' cell phone use while driving legislation. The exposure was
      presence of a universal hand-held cell phone ban at time of observation. Logistic
      regression was used to assess the odds of drivers having a hand-held cell phone
      conversation. Sub-groups differences were assessed using models with interaction
      terms. RESULTS: When universal hand-held cell phone bans were effective, hand
      held cell phone conversations were lower across all driver demographic sub-groups
      and regions. Sub-group differences existed among the sexes (p-value, <0.0001) and
      regions (p-value, 0.0003). Compared to states without universal hand-held cell
      phone bans, the adjusted odds ratio (aOR) of a driver hand-held phone
      conversation was 0.34 [95% confidence interval (CI): 0.28, 0.41] for females
      versus 0.47 (CI 0.40, 0.55) for males and 0.31 (CI 0.25, 0.38) for drivers in
      Western states compared to 0.47 (CI 0.30, 0.72) in the Northeast and 0.50 (CI
      0.38, 0.66) in the South. CONCLUSIONS: The presence of universal hand-held cell
      phone bans were associated lower hand-held cell phone conversations across all
      driver sub-groups and regions. Hand-held phone conversations were particularly
      lower among female drivers and those from Western states when these bans were in
      effect. Public health interventions concerning hand-held cell phone use while
      driving could reasonably target all drivers.

PMID- 28499427
TI  - Pars plana vitrectomy with partial tamponade of filtered air in Rhegmatogenous
      retinal detachment caused by superior retinal breaks.
AB  - BACKGROUND: To investigate the anatomic and functional outcomes of pars plana
      vitrectomy (PPV) with partial tamponade of filtered air for rhegmatogenous
      retinal detachment (RRD) caused by superior retinal breaks. METHODS:
      Retrospective, comparative, consecutive case series study. Patients with RRD
      caused by superior retinal breaks undergone PPV with partial tamponade (Group A)
      and whole tamponade (Group B) of filtered air were included. The main outcomes
      were primary and final success rates, best corrected visual acuity (BCVA), and
      rate of postoperative cataract surgery. RESULTS: Forty-one patients (41 eyes)
      were included in Group A and 36 patients (36 eyes) were included in Group B.
      There were no significant differences in primary or final success rates between
      Groups A and B (P = 0.618 and P = 1.000, respectively). The patients in Group A
      experienced quicker postoperative vision improvement (from the Week 1 follow-up)
      than the patients in Group B (from the Month 3 follow-up). The postoperative
      cataract surgery rate of Group A (7/31) was lower than that of Group B (13/26) (P
      = 0.031). CONCLUSIONS: PPV with partial tamponade of air is effective in
      achieving a high anatomic success rate, quicker postoperative vision improvement,
      and lower rate of postoperative cataract surgery in RRD caused by superior
      retinal breaks.

PMID- 28499428
TI  - Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy
      in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant
      treatment for rectal cancer.
AB  - BACKGROUND: Neoadjuvant fluoropirimidine (5FU)-based chemoradiotherapy (CRT) has
      been considered the standard of care for locally advanced rectal cancer (LARC).
      Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is
      still debated. We conducted a meta-analysis to evaluate the role of OXP in this
      patient population. METHODS: Literature searches were carried out in PubMed,
      Medline and Scopus databases. End points were overall survival (OS), disease free
      survival (DFS), local failure (LF) and distant failure (DF). Odd ratio (OR) with
      95% confidence interval (CI) was calculated using random effects model. RESULTS:
      Four randomized trials were included. Patients treated with OXP-5FU CRT had
      significantly decreased DF (OR = 0.76; 95% CI, 0.60 to 0.97; p = 0.03) compared
      to standard CRT. OS, DFS and LF were not significantly different between groups.
      CONCLUSIONS: OXP significantly decreased DF, but does not improve OS e DFS
      compared to 5FU CRT. Precise role of OXP in neoadjuvant setting of LARC remains
      to be determined.

PMID- 28499429
TI  - Parental work absenteeism is associated with increased symptom complaints and
      school absence in adolescent children.
AB  - BACKGROUND: Previous studies have proposed that having parents out of work may
      influence adolescent illness behaviour and school attendance. However, prior
      research investigating this question has been limited by retrospective reporting
      and case control studies. In a large epidemiological study we investigated
      whether parental work absence was associated with symptom complaints and
      increased school absenteeism in adolescents. METHODS: We analysed data from a
      large epidemiological study of 10,243 Norwegian adolescents aged 16-19.
      Participants completed survey at school, which included demographic data,
      parental work absence and current health complaints. An official registry
      provided school attendance data. RESULTS: Parental work absence was significantly
      related to the number of adolescent symptom complaints as well as school
      absenteeism. Having a father out of work was associated with an increased
      likelihood of being in the highest quartile of symptom reporting by an odds-ratio
      of 2.2 and mother by 1.6 (compared to the lowest quartile). Similarly, parental
      work absenteeism was associated with an increased likelihood of being in the
      highest quartile for school absence by an odds-ratio of 1.9 for a father being
      out of work and 1.5 for a mother out of work. We found that the number of
      adolescent symptom complaints mediated the relationship between parental work
      absenteeism and school absenteeism. CONCLUSION: We found that parental work
      absence was significantly associated with the number of adolescent symptom
      complaints and school absenteeism. The results suggest that parents may play a
      critical modelling role in the intergenerational transmission of illness and
      disability behaviour.

PMID- 28499430
TI  - Genome-wide DNA methylation analysis in lung fibroblasts co-cultured with silica
      exposed alveolar macrophages.
AB  - BACKGROUND: Exposure to crystalline silica is considered to increase the risk of
      lung fibrosis. The primary effector cell, the myofibroblast, plays an important
      role in the deposition of extracellular matrix (ECM). DNA methylation change is
      considered to have a potential effect on myofibroblast differentiation.
      Therefore, the present study was designed to investigate the genome-wide DNA
      methylation profiles of lung fibroblasts co-cultured with alveolar macrophages
      exposed to crystalline silica in vitro. METHODS: AM/fibroblast co-culture system
      was established. CCK8 was used to assess the toxicity of AMs. mRNA and protein
      expression of collagen I, alpha-SMA, MAPK9 and TGF-beta1 of fibroblasts after AMs
      exposed to 100 MUg /ml SiO2 for 0-, 24-, or 48 h were determined by means of
      quantitative real-time PCR, immunoblotting and immunohistochemistry. Genomic DNA
      of fibroblasts was isolated using MeDIP-Seq to sequence. R software, GO, KEGG and
      Cytoscape were used to analyze the data. RESULTS: SiO2 exposure increased the
      expression of collagen I and alpha-SMA in fibroblasts in co-culture system.
      Analysis of fibroblast methylome identified extensive methylation changes
      involved in several signaling pathways, such as the MAPK signaling pathway and
      metabolic pathways. Several candidates, including Tgfb1 and Mapk9, are hubs who
      can connect the gene clusters. MAPK9 mRNA expression was significantly higher in
      fibroblast exposed to SiO2 in co-culture system for 48 h. MAPK9 protein
      expression was increased at both 24-h and 48-h treatment groups. TGF-beta1 mRNA
      expression of fibroblast has a time-dependent manner, but we didn't observe the
      TGF-beta1 protein expression. CONCLUSION: Tgfb1 and Mapk9 are helpful to explore
      the mechanism of myofibroblast differentiation. The genome-wide DNA methylation
      profiles of fibroblasts in this experimental silicosis model will be useful for
      future studies on epigenetic gene regulation during myofibroblast
      differentiation.

PMID- 28499431
TI  - Minimal invasive percutaneous plate osteosynthesis (MIPPO) through deltoid
      pectoralis approach for the treatment of elderly proximal humeral fractures.
AB  - BACKGROUND: Current treatments for proximal humeral fractures include
      conservative treatment, conventional open reduction internal fixation (ORIF) and
      MIPPO through deltoid-splitting approach. The aim of this study was to evaluate
      the clinical outcome of MIPPO versus ORIF via the deltoid-pectoralis approach in
      elderly patients with proximal humeral fractures. METHODS: Thirty-six patients
      with proximal humeral fractures were enrolled in this study. Following the
      randomized block and single-blinded principle, the patients were assigned to two
      groups and treated with either conventional ORIF or MIPPO, both through the
      deltoid-pectoralis approach. Surgical outcomes were evaluated by the NEER score,
      Constant-Murley score, blood loss, length of operation, radiological imaging and
      clinical examination. The patients were followed up for 4-24 (mean 10) months.
      RESULTS: According to Constant-Murley score, the surgical outcome was excellent
      in 14 cases, satisfactory in 2 cases and unsatisfactory in one case in MIPPO
      group versus 10, 5 and 4 in conventional ORIF group. MIPPO was significantly
      advantageous over conventional ORIF in terms of NEER score, Constant-Murley,
      length of operation and intraoperative blood loss. In addition, MIPPO was also
      more advantageous in several indexes in patients with BMI > 26.0 and NEER type
      III fracture. CONCLUSION: The results of our study have demonstrated that MIPPO
      through the deltoid-pectoralis approach is an effective alternative for the
      treatment of proximal humeral fractures in elderly patients. TRIAL REGISTRATION:
      The trial registration number (TRN): ChiCTR-INR-17011098 (retrospectively
      registered at 2017-04-09).

PMID- 28499432
TI  - Development and evaluation of a community-based buprenorphine treatment
      intervention.
AB  - BACKGROUND: The majority of Americans with opioid use disorder remain out of
      treatment. Operating in 33 states, Washington DC, and Puerto Rico, harm reduction
      agencies, which provide sterile syringes and other health services to people who
      inject drugs, are a key venue to reach out-of-treatment opioid users. Aiming to
      link out-of-treatment individuals with opioid use disorder to buprenorphine
      treatment, we developed a community-based buprenorphine treatment (CBBT)
      intervention in collaboration with New York City harm reduction agencies.
      METHODS: Intervention development included formative data collection, feasibility
      testing at one harm reduction agency, and pilot testing for preliminary
      effectiveness at a second harm reduction agency. We used a pre-post design for
      both feasibility and pilot testing. In the CBBT intervention, we trained harm
      reduction agency staff to provide (1) buprenorphine education, (2) motivational
      interviewing, (3) referrals to buprenorphine-prescribing doctors, and (4)
      treatment retention support. We assessed feasibility by measuring staff
      satisfaction with the intervention and changes in knowledge about buprenorphine.
      We assessed preliminary effectiveness by comparing rates of buprenorphine
      initiation among groups of harm reduction agency clients before and after
      intervention implementation. RESULTS: Among staff members at the first harm
      reduction agency, knowledge increased from 52% correct answers pre-intervention
      to 79% correct post-intervention. Among clients at the second harm reduction
      agency, initiation of buprenorphine treatment was low and did not differ between
      pre- and post-intervention groups. CONCLUSIONS: The CBBT intervention was
      feasible and well-received, but initiation of buprenorphine treatment among harm
      reduction agency clients was low. More robust interventions may be necessary to
      increase initiation of buprenorphine treatment.

PMID- 28499433
TI  - ServAR: An augmented reality tool to guide the serving of food.
AB  - BACKGROUND: Accurate estimation of food portion size is a difficult task. Visual
      cues are important mediators of portion size and therefore technology-based aids
      may assist consumers when serving and estimating food portions. The current study
      evaluated the usability and impact on estimation error of standard food servings
      of a novel augmented reality food serving aid, ServAR. METHODS: Participants were
      randomised into one of three groups: 1) no information/aid (control); 2) verbal
      information on standard serving sizes; or 3) ServAR, an aid which overlayed
      virtual food servings over a plate using a tablet computer. Participants were
      asked to estimate the standard serving sizes of nine foods (broccoli, carrots,
      cauliflower, green beans, kidney beans, potato, pasta, rice, and sweetcorn) using
      validated food replicas. Wilcoxon signed-rank tests compared median served
      weights of each food to reference standard serving size weights. Percentage error
      was used to compare the estimation of serving size accuracy between the three
      groups. All participants also performed a usability test using the ServAR tool to
      guide the serving of one randomly selected food. RESULTS: Ninety adults (78.9%
      female; a mean (95%CI) age 25.8 (24.9-26.7) years; BMI 24.2 (23.2-25.2) kg/m2)
      completed the study. The median servings were significantly different to the
      reference portions for five foods in the ServAR group, compared to eight foods in
      the information only group and seven foods for the control group. The cumulative
      proportion of total estimations per group within +/-10%, +/-25% and +/-50% of the
      reference portion was greater for those using ServAR (30.7, 65.2 and 90.7%;
      respectively), compared to the information only group (19.6, 47.4 and 77.4%) and
      control group (10.0, 33.7 and 68.9%). Participants generally found the ServAR
      tool easy to use and agreed that it showed potential to support optimal portion
      size selection. However, some refinements to the ServAR tool are required to
      improve the user experience. CONCLUSIONS: Use of the augmented reality tool
      improved accuracy and consistency of estimating standard serve sizes compared to
      the information only and control conditions. ServAR demonstrates potential as a
      practical tool to guide the serving of food. Further evaluation across a broad
      range of foods, portion sizes and settings is warranted.

PMID- 28499434
TI  - Development of a novel immunochromatographic lateral flow assay specific for
      Mycobacterium bovis cells and its application in combination with immunomagnetic
      separation to test badger faeces.
AB  - BACKGROUND: The European badger is an important wildlife reservoir of
      Mycobacterium bovis implicated in the spread of bovine tuberculosis in the United
      Kingdom and Ireland. Infected badgers are known to shed M. bovis in their urine
      and faeces, which may contaminate the environment. To aid bovine tuberculosis
      control efforts novel diagnostic tests for detecting infected and shedding
      badgers are needed. We proposed development of a novel, rapid
      immunochromatographic lateral flow device (LFD) as a non-invasive test to detect
      M. bovis cells in badger faeces. Its application in combination with
      immunomagnetic separation (IMS) to detect Mycobacterium bovis cells in badger
      faeces is reported here. RESULTS: A novel prototype LFD for M. bovis cells was
      successfully developed, with unique specificity for M. bovis and a limit of
      detection 50% (LOD50%) of 1.7 * 104 M. bovis cells/ml. When IMS was employed to
      selectively capture and concentrate M. bovis cells from badger faeces prior to
      LFD testing, the LOD50% of the IMS-LFD assay was 2.8 * 105 M. bovis cells/ml
      faecal homogenate. Faeces samples collected from latrines at badger setts in a
      region of endemic bovine tuberculosis infection were tested; 78 (18%) of 441
      samples tested IMS-LFD assay positive, whereas 140 (32%) tested IMS-qPCR positive
      (Kappa agreement -0.009 +/- 0.044, p = 0.838). Subsequently, when 130 faeces
      samples from live captured, or captive, badgers of known infection status (on the
      basis of StatPak, interferon-gamma and/or culture results) were tested, the IMS
      LFD assay had higher relative diagnostic specificity (Sp 0.926), but poorer
      relative diagnostic sensitivity (Se 0.081), than IMS-qPCR (Sp 0.706, Se 0.581)
      and IMS-culture (Sp 0.794, Se 0.436). CONCLUSIONS: The novel IMS-LFD assay,
      although very specific for M. bovis, has low analytical sensitivity (indicated by
      the LOD50%) and would only detect badgers shedding high numbers of M. bovis (>104
      5 cells/g) in their faeces. The novel LFD would, therefore, have limited value as
      a non-invasive test for badger TB surveillance purposes but it may have value for
      alternative veterinary diagnostic applications.

PMID- 28499435
TI  - Parasite fauna of the Antarctic dragonfish Parachaenichthys charcoti
      (Perciformes: Bathydraconidae) and closely related Bathydraconidae from the
      Antarctic Peninsula, Southern Ocean.
AB  - BACKGROUND: As members of the Notothenioidei - the dominant fish taxon in
      Antarctic waters - the family Bathydraconidae includes 12 genera and 17 species.
      The knowledge of these species inhabiting an isolated environment is rather
      fragmentary, including their parasite fauna. Studies on fish hosts and their
      associated parasites can help gain insights into even remote ecosystems and be
      used to infer ecological roles in food webs; however, ecological studies on the
      Bathydraconidae are scarce. RESULTS: In this study, stomach contents and parasite
      fauna of the Antarctic dragonfish species Parachaenichthys charcoti (n = 47
      specimens) as well as of Gerlachea australis (n = 5), Gymnodraco acuticeps (n =
      9) and Racovitzia glacialis (n = 6) were examined. The parasite fauna of P.
      charcoti consisted of eight genera represented by 11 species, with three of them
      being new host records. Overall, 24 parasite genera and 26 species were found in
      the sampled fish, including eleven new host records. CONCLUSION: Analyses
      revealed that the majority of the parasite species found in the different fish
      hosts are endemic to Antarctic waters and are characterized by a broad host
      range. These findings are evidence for the current lack of knowledge and the need
      for further parasitological studies of fish species in this unique habitat.

PMID- 28499436
TI  - Inequality in healthcare costs between residing and non-residing patients:
      evidence from Vietnam.
AB  - BACKGROUND: Place of residence has been shown to impact health. To date, however,
      previous studies have only focused on the variability in health outcomes and
      healthcare costs between urban and rural patients. This study takes a different
      approach and investigates cost inequality facing non-residing patients - patients
      who do not reside in the regions in which the hospitals are located.
      Understanding the sources for this inequality is important, as they are directly
      related to healthcare accessibility in developing countries. METHODS: The causal
      impact of residency status on individual healthcare spending is documented with a
      quasi-experimental design. The propensity score matching method is applied to a
      unique patient-level dataset (n = 900) collected at public general and specialist
      hospitals across North Vietnam. RESULTS: Propensity score matching shows that
      Vietnamese patients who do not reside in the regions in which the hospitals are
      located are expected to pay about 15 million Vietnamese dongs (approximately 750
      USD) more than those who do, a sizable gap, given the distribution of total
      healthcare costs for the overall sample. This estimate is robust to alternative
      matching specifications. The obtained discrepancy is empirically attributable to
      the differences in three potential contributors, namely spending on accompanying
      relatives, "courtesy funds," and days of hospitalization. CONCLUSIONS: The
      present study finds that there is significant inequality in healthcare spending
      between residing and non-residing patients at Vietnamese hospitals and that this
      discrepancy can be partially explained by both institutional and non
      institutional factors. These factors signal practical channels through which
      policymakers can improve healthcare accessibility.

PMID- 28499437
TI  - The effect of hemostatic dressing prototypes for the uniformed services on
      selected blood coagulation parameters in pigs.
AB  - BACKGROUND: Serious injuries accompanied by severe bleeding are life-threatening.
      Post-traumatic hemorrhage involves the risk of developing coagulopathy.
      Hemostatic dressings are widely used to minimize bleeding. The application of
      procoagulants in control of hemorrhage may lead to thrombosis or disseminated
      intravascular coagulation. The aim of this study was to evaluate the effect of
      hemostatic dressing prototypes on the porcine coagulation system. RESULTS:
      Fibrinogen and D-dimer concentrations were significantly higher in the
      experimental groups where hemostatic dressings were used in comparison with the
      control group. Considerable differences in antithrombin III activity and thrombin
      antithrombin complex concentrations were also observed between groups.
      CONCLUSIONS: The hemostatic dressing comprising modified seton impregnated with
      18.0 g/m2 of procoagulant was most effective in preserving the physiological
      equilibrium between fibrinogenesis and fibrinolysis.

PMID- 28499438
TI  - Early developed ASD (adjacent segmental disease) in patients after surgical
      treatment of the spine due to cancer metastases.
AB  - BACKGROUND: The causes of ASD are still relatively unknown. Correlation between
      clinical status of patients and radiological MRI findings is of primary
      importance. The radiological classifications proposed by Pfirmann and Oner are
      most commonly used to assess intradiscal degenerative changes. The aim of the
      study was to assess the influence of the extension of spine fixation on the risk
      of developing ASD in a short time after surgery. METHODS: A total of 332 patients
      with spinal tumors were treated in our hospital between 2010 and 2013. Of these
      patients, 287 underwent surgeries. A follow-up MRI examination was performed 12
      months after surgical treatment. The study population comprised of 194 patients.
      Among metastases, breast cancer was predominant (29%); neurological deficits were
      detected in 76 patients. Metastases were seen in the thoracic (45%) and lumbar
      (30%) spine; in 25% of cases, they were of multisegmental character. Pathological
      fractures concerned 88% of the patients. Statistical calculations were made using
      the chi2 test. Statistical analysis was done using the Statistica v. 10 software.
      A p value <0.05 was accepted as statistically significant. The study population
      was divided on seven groups according to applied treatment. RESULTS: Clinical
      signs of ASD were noted in only seven patients. Two patients had symptoms of
      nerve root irritation in the lumbar spine. Twenty-two patients (11%) were
      diagnosed with ASD according to the MRI classifications by Oner, Rijt, and Ramos,
      while the more sensitive Pfirmann classification allowed to detect the disease in
      46 patients (24%). Healthy or almost healthy discs of Oner type I correlated with
      the criteria of Pfirmann types II and III. The percentage of the incidence of ASD
      diagnosed 1 year after the surgery using the Pfirmann classifications was
      significantly higher than diagnosed according to the clinical examination.
      CONCLUSIONS: The incidence of ASD in patients after spine surgeries due to cancer
      metastases does not differ between the study groups. ASD detectability based on
      clinical signs is significantly lower than ASD detectability based on MR images
      according to the system by Pfirrmann et.al. ASD risk increase among patients with
      multilevel fixation.

PMID- 28499440
TI  - A feasibility randomised controlled trial of extended brief intervention for
      alcohol misuse in adults with mild to moderate intellectual disabilities living
      in the community; The EBI-LD study.
AB  - BACKGROUND: Extended brief interventions (EBIs) are effective in targeting
      alcohol misuse in the general population. However, little is known of the effects
      of EBI in adults with intellectual (also known as learning) disabilities. In this
      feasibility trial we compared EBI with usual care for alcohol misuse in adults
      with mild to moderate Intellectual Disability (ID). METHODS: The study took place
      in three community ID networks of services in England. Participants aged 18-65
      years with reported alcohol problems, a score >=8 on the Alcohol Use Disorder
      Identification Test (AUDIT), and IQ <70 (+/5%CI) were recruited and were randomly
      allocated to either EBI (five weekly sessions and one follow-up at 8 weeks) and
      usual care or usual care alone. Research assistants were blind to arm allocation.
      Research assessments took place at baseline, 2 and 3 months. The primary outcome
      was reduction in alcohol consumption measured by the AUDIT. Preliminary health
      economic analysis was performed to investigate the costs of delivering EBI and
      the feasibility of a cost-effectiveness analysis in a full trial. The trial is
      closed. RESULTS: Participants were recruited from January 2014 to August 2015.
      Thirty individuals were randomised (15 in each arm) and provided primary outcome
      data. In regard to harmful drinking, at baseline, all the participants exceeded
      the relevant threshold. At 8 weeks, the proportion of participants with harmful
      drinking had decreased to 60% for both groups, and at 12 weeks it had decreased
      by 66 degrees 7% and 46 degrees 7% for the intervention and the control groups,
      respectively. The unit cost for the delivery of EBI is L430. CONCLUSIONS:
      Recruitment to this trial has been proven challenging as prevalence of alcohol
      misuse in the targeted population was lower than anticipated. EBI may provide an
      effective low-intensity treatment for this population. Participants' and carers'
      feedback on their experience was overall positive. Further work needs to be
      undertaken to ascertain the group of participants that should be participating in
      a future definitive trial. TRIAL REGISTRATION: Psychological Intervention Alcohol
      Misuse Learning Disability; isrctn.com, identifier: ISRCTN58783633 . Registered
      on 17 December 2013.

PMID- 28499439
TI  - The role of TGF-beta and its crosstalk with RAC1/RAC1b signaling in breast and
      pancreas carcinoma.
AB  - This article focusses on the role of TGF-beta and its signaling crosstalk with
      the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic
      carcinoma. The aggressive nature of these tumor types is mainly due to metastatic
      dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor
      microenvironment and the ability of the tumor cells to undergo epithelial
      mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These
      processes are controlled entirely or in part by TGF-beta and the small RHO GTPase
      RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data
      from our and other studies point to signaling crosstalk between TGF-beta and RAC1
      and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based
      on the exciting observation that RAC1b functions as an endogenous inhibitor of
      RAC1, we propose a model on how the relative abundance or activity of RAC1 and
      RAC1b in the tumor cells may determine their responses to TGF-beta and,
      ultimately, the metastatic capacity of the tumor.

PMID- 28499441
TI  - Chromosomal abnormalities: subgroup analysis by maternal age and perinatal
      features in zhejiang province of China, 2011-2015.
AB  - BACKGROUND: Recently, the prevalence of chromosomal abnormalities (CA) increased
      as the increasing proportion of mothers with advanced age. We aimed to explore
      the prevalence of CA in relation to maternal age and perinatal features. METHODS:
      A retrospective study was performed based on provincial birth defects
      surveillance data. The relative risk (RR) and 95% confidence interval (CI) were
      used to calculate maternal age-specific rates of CA. Socio-demographic
      characteristics of mothers and perinatal features were listed. RESULTS: The total
      prevalence of CA was 6.38 per 10,000 births, which increased per 10,000 births
      linearly from 4.02 in 2011 to 9.13 in 2015 (x 2line-trend =52.69, p < 0.001).
      During this period, the prevalence for CA per 10,000 births among women over 35
      years old increased from 15.34 in 2011 to 33.82 in 2015 (x 2line-trend =115121.6,
      p < 0.001). The RR for overall CA, trisomy 21(T21), trisomy 18(T18) and others in
      mothers 35 years or older were 6.64 (95% CI 5.55 ~ 7.93), 6.83 (95% CI 5.63 ~
      8.30), 4.06 (95% CI 2.09 ~ 7.90) and 7.54 (95% CI 4.02 ~ 14.11) respectively in
      comparison to mothers aged 25-29 years old. The stillbirths rate for total CA was
      76.45%. T21 and T18 were strongly associated with multiple anomalies, especially
      congenital heart abnormalities. CONCLUSIONS: The prevalence of CA increased as
      maternal age increased. Cases with CA were associated with other congenital
      defects and high mortality risk.

PMID- 28499443
TI  - Erratum to: DeepCpG: accurate prediction of single-cell DNA methylation states
      using deep learning.

PMID- 28499442
TI  - Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian
      cancer cells.
AB  - BACKGROUND: Chemotherapy resistance is one of the major factors contributing to
      mortality from human epithelial ovarian cancer (EOC). Identifying drugs that can
      effectively kill chemotherapy-resistant EOC cells would be a major advance in
      reducing mortality. Glycosylated antitumour ether lipids (GAELs) are synthetic
      glycolipids that are cytotoxic to a wide range of cancer cells. They appear to
      induce cancer cell death in an apoptosis-independent manner. METHODS: Herein, the
      effectiveness of two GAELs, GLN and MO-101, in killing chemotherapy-sensitive and
      -resistant EOC cells lines and primary cell samples was tested using monolayer,
      non-adherent aggregate, and non-adherent spheroid cultures. RESULTS: Our results
      show that EOC cells exhibit a differential sensitivity to the GAELs. Strikingly,
      both GAELs are capable of inducing EOC cell death in chemotherapy-sensitive and 
      resistant cells grown as monolayer or non-adherent cultures. Mechanistic studies
      provide evidence that apoptotic-cell death (caspase activation) contributes to,
      but is not completely responsible for, GAEL-induced cell killing in the A2780-cp
      EOC cell line, but not primary EOC cell samples. CONCLUSIONS: Studies using
      primary EOC cell samples supports previously published work showing a GAEL
      induced caspase-independent mechanism of death. GAELs hold promise for
      development as novel compounds to combat EOC mortality due to chemotherapy
      resistance.

PMID- 28499445
TI  - Vision-related quality of life following glaucoma filtration surgery.
AB  - BACKGROUND: To evaluate vision-related quality of life (VR-QOL) following
      glaucoma filtration surgery. METHODS: A total of 103 glaucoma patients scheduled
      to undergo glaucoma filtration surgery. Prior to and at three months after
      glaucoma filtration surgery, trabeculectomy or EX-PRESS, all patients completed
      the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). A
      total of 48 patients underwent combined cataract and filtration surgery. The
      clinical data collected pre- and postoperatively included best-corrected visual
      acuity (BCVA) and intraocular pressure (IOP). RESULTS: The IOP decreased
      significantly from 19.0 +/- 8.1 mmHg to 9.7 +/- 3.9 mmHg (P < 0.001).
      Preoperative VFQ-25 composite score (65.8 +/- 15.6) was similar to the
      postoperative score (67.8 +/- 16.6). A significantly improved VFQ-25 composite
      score (pre: 63.2 +/- 17.1, post: 67.7 +/- 17.8; P = 0.001) was observed in the
      patients who underwent combined cataract and filtration surgery. There was a
      significant association between the BCVA changes in the operated eye and the
      changes in the VFQ-25 composite score (r = -0.315, P = 0.003). CONCLUSIONS:
      Although glaucoma filtration surgery by itself did not decrease the VR-QOL in
      glaucoma patients, there was significant improvement in the VR-QOL after the
      patients underwent combined cataract and glaucoma filtration surgery.

PMID- 28499444
TI  - A French national breast and thyroid cancer screening programme for survivors of
      childhood, adolescent and young adult (CAYA) cancers - DeNaCaPST programme.
AB  - BACKGROUND: Survival of childhood, adolescent and young adult (CAYA) cancers has
      increased with progress in the management of the treatments and has reached more
      than 80% at 5 years. Nevertheless, these survivors are at great risk of second
      cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non
      interventional study whose aim is to organize a national screening for thyroid
      cancer and breast cancer in survivors of CAYA cancers. It will study the
      compliance with international recommendations, with the aim, regarding a breast
      screening programme, of offering for every woman living in France, at equal risk,
      an equal screening. METHOD: DeNaCaPST trial is coordinated by the INSERM 1018
      unit in cooperation with the LEA (French Childhood Cancer Survivor Study for
      Leukaemia) study's coordinators, the long term follow up committee and the
      paediatric radiation committee of the SFCE (French Society of Childhood Cancers).
      A total of 35 centres spread across metropolitan France and la Reunion will
      participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central
      registry will be interrogated to identify eligible patients. To participate,
      centers agreed to perform a complete "long-term follow-up consultations"
      according to good clinical practice and the guidelines of the SFCE (French
      Society of Children Cancers). DISCUSSION: As survival has greatly improved in
      childhood cancers, detection of therapy-related malignancies has become a
      priority even if new radiation techniques will lead to better protection for
      organs at risk. International guidelines have been put in place because of the
      evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is
      based on these international recommendations but it is important to recognize
      that they are based on expert consensus opinion and are supported by neither
      nonrandomized observational studies nor prospective randomized trials in this
      specific population. Over-diagnosis is a phenomenon inherent in any screening
      program and therefore such programs must be evaluated.

PMID- 28499447
TI  - Gender difference in utilization willingness of institutional care among the
      single seniors: evidence from rural Shandong, China.
AB  - BACKGROUND: Institutional care has become an urgent issue in rural China. Rural
      single seniors, compared with their counterparts, have lower income and are more
      vulnerable. Gender is also a significant factor determining long-term
      institutional care. This study is designed to examine the gender difference
      towards utilization willingness of institutional care among rural single seniors.
      METHODS: A total of 505 rural single seniors were included in the analysis.
      Binary logistic regression model was used to examine the gender difference
      towards utilization willingness for institutional care, and also to identify the
      determinants of the utilization willingness for institutional care among rural
      single male and female seniors. RESULTS: Our study found that about 5.7% rural
      single seniors had willingness for institutional care in Shandong, China. Single
      females were found to be less willing for institutional care than single males in
      rural areas (OR = 0.19; 95 CI 0.06-0.57). It's also found that psychological
      stress was associated with institutionalization willingness in both single males
      (P = 0.045) and single females (P = 0.013) in rural China. The rural single
      seniors who lived alone were found to be more willing for institutional care both
      in males (P = 0.032) and females (P = 0.002) compared with those who lived with
      children or others. CONCLUSIONS: This study found that there was a gender
      difference towards utilization willingness for institutional care among single
      seniors in rural China. Factors including psychological stress and living
      arrangements were determinants of institutionalization willingness both in single
      males and females. Targeted policies should be made for rural single seniors of
      different gender.

PMID- 28499446
TI  - Genome sequence of Shigella flexneri strain SP1, a diarrheal isolate that encodes
      an extended-spectrum beta-lactamase (ESBL).
AB  - BACKGROUND: Shigellosis is the most common cause of gastrointestinal infections
      in developing countries. In China, the species most frequently responsible for
      shigellosis is Shigella flexneri. S. flexneri remains largely unexplored from a
      genomic standpoint and is still described using a vocabulary based on biochemical
      and serological properties. Moreover, increasing numbers of ESBL-producing
      Shigella strains have been isolated from clinical samples. Despite this, only a
      few cases of ESBL-producing Shigella have been described in China. Therefore, a
      better understanding of ESBL-producing Shigella from a genomic standpoint is
      required. In this study, a S. flexneri type 1a isolate SP1 harboring blaCTX-M-14,
      which was recovered from the patient with diarrhea, was subjected to whole genome
      sequencing. RESULTS: The draft genome assembly of S. flexneri strain SP1
      consisted of 4,592,345 bp with a G+C content of 50.46%. RAST analysis revealed
      the genome contained 4798 coding sequences (CDSs) and 100 RNA-encoding genes. We
      detected one incomplete prophage and six candidate CRISPR loci in the genome. In
      vitro antimicrobial susceptibility testing demonstrated that strain SP1 is
      resistant to ampicillin, amoxicillin/clavulanic acid, cefazolin, ceftriaxone and
      trimethoprim. In silico analysis detected genes mediating resistance to
      aminoglycosides, beta-lactams, phenicol, tetracycline, sulphonamides, and
      trimethoprim. The bla CTX-M-14 gene was located on an IncFII2 plasmid. A series
      of virulence factors were identified in the genome. CONCLUSIONS: In this study,
      we report the whole genome sequence of a blaCTX-M-14-encoding S. flexneri strain
      SP1. Dozens of resistance determinants were detected in the genome and may be
      responsible for the multidrug-resistance of this strain, although further
      confirmation studies are warranted. Numerous virulence factors identified in the
      strain suggest that isolate SP1 is potential pathogenic. The availability of the
      genome sequence and comparative analysis with other S. flexneri strains provides
      the basis to further address the evolution of drug resistance mechanisms and
      pathogenicity in S. flexneri.

PMID- 28499448
TI  - Comparison of demographic characteristics and psychiatric comorbidity among
      methamphetamine-, heroin- and methamphetamine-heroin co- dependent males in
      Hunan, China.
AB  - BACKGROUND: There is little research of psychiatric comorbidity differences among
      people with different types of drug dependence in Chinese population. We explored
      demographic and comorbid psychiatric differences among methamphetamine- dependent
      males (MDs), heroin-dependent males (HDs) and methamphetamine and heroin co
      dependent males (M/HDs) in Hunan province, China. METHODS: A cross-sectional,
      structured and clinical interview method was used to examine differences in DSM
      IV-TR Axis I Disorders among 346 MDs, 698 HDs and 247 M/HDs from three compulsory
      rehabilitation centers and two voluntary rehabilitation centers in Hunan.
      RESULTS: MDs and M/HDs were younger, more likely to choose inhalation
      administration, less likely to have a family history of substance use, less
      likely to have undergone detoxification treatment, had higher incomes and shorter
      duration of drug use than HDs. Overall, methamphetamine-dependence related to
      higher rates of current and lifetime psychotic disorders, lifetime hallucinogen
      use disorders. Heroin-dependence related to higher rates of current and lifetime
      substance-induced mood disorders, sedative/hypnotic/anxiolytic and other drug use
      disorders and current alcohol use disorder. For M/HDs, they were more likely to
      have any other lifetime substance use disorders than MDs and HDs. CONCLUSIONS:
      There were substantial differences in epidemiological characteristics and
      comorbidity among MD, HD and M/HD groups, which highlights the urgent need to
      develop treatment services and policies for drug-specific users in China.

PMID- 28499449
TI  - PERK induces resistance to cell death elicited by endoplasmic reticulum stress
      and chemotherapy.
AB  - BACKGROUND: Nutrient deprivation, hypoxia, radiotherapy and chemotherapy induce
      endoplasmic reticulum (ER) stress, which activates the so-called unfolded protein
      response (UPR). Extensive and acute ER stress directs the UPR towards activation
      of death-triggering pathways. Cancer cells are selected to resist mild and
      prolonged ER stress by activating pro-survival UPR. We recently found that drug
      resistant tumor cells are simultaneously resistant to ER stress-triggered cell
      death. It is not known if cancer cells adapted to ER stressing conditions acquire
      a chemoresistant phenotype. METHODS: To investigate this issue, we generated
      human cancer cells clones with acquired resistance to ER stress from ER stress
      sensitive and chemosensitive cells. RESULTS: ER stress-resistant cells were cross
      resistant to multiple chemotherapeutic drugs: such multidrug resistance (MDR) was
      due to the overexpression of the plasma-membrane transporter MDR related protein
      1 (MRP1). Gene profiling analysis unveiled that cells with acquired resistance to
      ER stress and chemotherapy share higher expression of the UPR sensor protein
      kinase RNA-like endoplasmic reticulum kinase (PERK), which mediated the erythroid
      derived 2-like 2 (Nrf2)-driven transcription of MRP1. Disrupting PERK/Nrf2 axis
      reversed at the same time resistance to ER stress and chemotherapy. The inducible
      silencing of PERK reduced tumor growth and restored chemosensitivity in resistant
      tumor xenografts. CONCLUSIONS: Our work demonstrates for the first time that the
      adaptation to ER stress in cancer cells produces a MDR phenotype. The
      PERK/Nrf2/MRP1 axis is responsible for the resistance to ER stress and
      chemotherapy, and may represent a good therapeutic target in aggressive and
      resistant tumors.

PMID- 28499450
TI  - Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit
      Polysialylation of NCAM in rhabdomyosarcoma tumor cells.
AB  - BACKGROUND: Polysialic acid (polySia) is a carbohydrate modification of the
      neural cell adhesion molecule (NCAM), which is implicated in neural
      differentiation and plays an important role in tumor development and metastasis.
      Polysialylation of NCAM is mediated by two Golgi-resident polysialyltransferases
      (polyST) ST8SiaII and ST8SiaIV. Intracellular antibodies (intrabodies; IB)
      expressed inside the ER and retaining proteins passing the ER such as cell
      surface receptors or secretory proteins provide an efficient means of protein
      knockdown. To inhibit the function of ST8SiaII and ST8SiaIV specific ER IBs were
      generated starting from two corresponding hybridoma clones. Both IBs
      alphaST8SiaII-IB and alphaST8SiaIV-IB were constructed in the scFv format and
      their functions characterized in vitro and in vivo. RESULTS: IBs directed against
      the polySTs prevented the translocation of the enzymes from the ER to the Golgi
      apparatus. Co-immunoprecipitation of ST8SiaII and ST8SiaIV with the corresponding
      IBs confirmed the intracellular interaction with their cognate antigens. In CHO
      cells overexpressing ST8SiaII and ST8SiaIV, respectively, the transfection with
      alphaST8SiaII-IB or alphaST8SiaIV-IB inhibited significantly the cell surface
      expression of polysialylated NCAM. Furthermore stable expression of ST8SiaII-IB,
      ST8SiaIV-IB and luciferase in the rhabdomyosarcoma cell line TE671 reduced cell
      surface expression of polySia and delayed tumor growth if cells were xenografted
      into C57BL/6 J RAG-2 mice. CONCLUSION: Data obtained strongly indicate that
      alphaST8SiaII-IB and alphaST8SiaIV-IB are promising experimental tools to analyze
      the individual role of the two enzymes during brain development and during
      migration and proliferation of tumor cells.

PMID- 28499451
TI  - Effects of annulus defects and implantation of poly(lactic-co-glycolic acid)
      (PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular
      injury disc degeneration.
AB  - BACKGROUND: Growth of nerve fibers has been shown to occur in a rabbit model of
      intravertebral disc degeneration (IVD) induced by needle puncture. As nerve
      growth may underlie the process of chronic pain in humans affected by disc
      degeneration, we sought to investigate the factors underlying nerve ingrowth in a
      minimally invasive annulotomy rabbit model of IVD by comparing the effects of
      empty disc defects with those of defects filled with poly(lactic-co-glycolic
      acid)/fibrin gel (PLGA) plugs. METHODS: New Zealand white rabbits (n = 24)
      received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The
      discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter;
      4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold
      containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and
      (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by
      radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG)
      content. Nerve ingrowth into the discs was assessed by immunostaining with the
      nerve marker protein gene product 9.5. RESULTS: Injured discs showed a
      progressive disc space narrowing with significant disc degeneration and
      proteoglycan loss, as confirmed by imaging results, molecular and compositional
      analysis, and histological examinations. In 16G punctured discs, nerve ingrowth
      was observed on the surface of scar tissue. In annular defects, nerve fibers were
      found to be distributed along small fissures within the fibrocartilaginous-like
      tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve
      fibers were observed growing deeper into the inner AF along the open annular
      track.  In addition, innervations scores showed significantly higher than those
      of punctured discs and empty defects. A limited vascular proliferation was found
      in the injured sites and regenerated tissues. CONCLUSIONS: Nerve ingrowth was
      significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible
      explanations include (i) annular fissures along the defect and early loss of
      proteoglycan may facilitate the ingrowth process and (ii) biodegradable
      PLGA/fibrin gel may promote adverse growth of nerves and blood vessels into
      deeper parts of injured disc. The rabbit annular defect model of disc
      degeneration appears suitable to investigate the effects of nerve ingrowth in
      relation to pain generation.

PMID- 28499453
TI  - Monitoring urban beaches with qPCR vs. culture measures of fecal indicator
      bacteria: Implications for public notification.
AB  - BACKGROUND: The United States Environmental Protection Agency has established
      methods for testing beach water using the rapid quantitative polymerase chain
      reaction (qPCR) method, as well as "beach action values" so that the results of
      such testing can be used to make same-day beach management decisions. Despite its
      numerous advantages over culture-based monitoring approaches, qPCR monitoring has
      yet to become widely used in the US or elsewhere. Considering qPCR results
      obtained on a given day as the best available measure of that day's water
      quality, we evaluated the frequency of correct vs. incorrect beach management
      decisions that are driven by culture testing. METHODS: Beaches in Chicago, USA,
      were monitored using E. coli culture and enterococci qPCR methods over 894 beach
      days in the summers of 2015 and 2016. Agreement in beach management using the two
      methods, after taking into account agreement due to chance, was summarized using
      Cohen's kappa statistic. RESULTS: No meaningful agreement (beyond that expected
      by chance) was observed between beach management actions driven by the two pieces
      of information available to beach managers on a given day: enterococci qPCR
      results ofsamples collected that morning and E. coli culture results of samples
      collected the previous day. The E. coli culture beach action value was exceeded
      3.4 times more frequently than the enterococci qPCR beach action value (22.6 vs.
      6.6% of beach-days). CONCLUSIONS: The largest evaluation of qPCR-based beach
      monitoring to date provides little scientific rationale for continued E. coli
      culture testing of beach water in our setting. The observation that the E. coli
      culture beach action value was exceeded three times as frequently as the
      enterococci qPCR beach action value suggests that, although the beach action
      values for bacteria using different measurement methods are thought to provide
      comparable information about health risk, this does not appear to be the case in
      all settings.

PMID- 28499454
TI  - Risk for intracranial pressure increase related to enclosed air in post
      craniotomy patients during air ambulance transport: a retrospective cohort study
      with simulation.
AB  - BACKGROUND: Post-craniotomy intracranial air can be present in patients scheduled
      for air ambulance transport to their home hospital. We aimed to assess risk for
      in-flight intracranial pressure (ICP) increases related to observed intracranial
      air volumes, hypothetical sea level pre-transport ICP, and different potential
      flight levels and cabin pressures. METHODS: A cohort of consecutive subdural
      hematoma evacuation patients from one University Medical Centre was assessed with
      post-operative intracranial air volume measurements by computed tomography.
      Intracranial pressure changes related to estimated intracranial air volume
      effects of changing atmospheric pressure (simulating flight and cabin pressure
      changes up to 8000 ft) were simulated using an established model for intracranial
      pressure and volume relations. RESULTS: Approximately one third of the cohort had
      post-operative intracranial air. Of these, approximately one third had
      intracranial air volumes less than 11 ml. The simulation estimated that the
      expected changes in intracranial pressure during 'flight' would not result in
      intracranial hypertension. For intracranial air volumes above 11 ml, the
      simulation suggested that it was possible that intracranial hypertension could
      develop 'inflight' related to cabin pressure drop. Depending on the pre-flight
      intracranial pressure and air volume, this could occur quite early during the
      assent phase in the flight profile.  DISCUSSION:  These findings support the idea
      that there should be radiographic verification of the presence or absence of
      intracranial air after craniotomy for patients planned for long distance air
      transport. CONCLUSIONS: Very small amounts of air are clinically inconsequential.
      Otherwise, air transport with maintained ground-level cabin pressure should be a
      priority for these patients.

PMID- 28499452
TI  - Current status and perspectives of patient-derived xenograft models in cancer
      research.
AB  - Cancers remain a major public health problem worldwide, which still require
      profound research in both the basic and preclinical fields. Patient-derived
      xenograft (PDX) models are created when cancerous cells or tissues from patients'
      primary tumors are implanted into immunodeficient mice to simulate human tumor
      biology in vivo, which have been extensively used in cancer research. The routes
      of implantation appeared to affect the outcome of PDX research, and there has
      been increasing applications of patient-derived orthotopic xenograft (PDOX)
      models. In this review, we firstly summarize the methodology to establish PDX
      models and then go over recent application and function of PDX models in basic
      cancer research on the areas of cancer characterization, initiation,
      proliferation, metastasis, and tumor microenvironment and in preclinical
      explorations of anti-cancer targets, drugs, and therapeutic strategies and
      finally give our perspectives on the future prospects of PDX models.

PMID- 28499455
TI  - Bovis Bacillus Calmette-Guerin (BCG) infection induces exosomal miRNA release by
      human macrophages.
AB  - BACKGROUND: Tuberculosis (TB) remains a significant global health concern and its
      diagnosis is challenging due to the limitations in the specificity and
      sensitivity of the current diagnostic tests. Exosomes are bioactive 30-100 nm
      vesicles produced by most cell types and are found in almost all human body
      fluids. Exosomal microRNAs (miRNAs) can transfer biological information between
      cells and tissues and may act as potential biomarkers in many diseases. In this
      pilot study, we assessed the miRNA profile of exosomes released from human
      monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus
      Calmette-Guerin (BCG). METHODS: Human monocytes were obtained from the peripheral
      blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM)
      phenotype using standard protocols. MDMs were infected with BCG or left
      uninfected as control. 72 h post-infection, exosomes were collected from the cell
      culture medium, RNA was isolated and RNA-seq performed. The raw reads were
      filtered to eliminate adaptor and primer sequences and the sequences were run
      against the mature human miRNA sequences available in miRBase. MicroRNAs were
      identified using an E value <0.01. miRNA network analysis was performed using the
      DIANA miRNA tool, miRDB and functional KEGG pathway analysis. RESULTS: Infection
      of MDMs with BCG leads to the release of several exosomal miRNAs. These included
      miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all
      of which were predicted to target metabolism and energy production-related
      pathways. CONCLUSIONS: This study provides evidence for the release of specific
      exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host
      pathogen interaction and subversion of host metabolic processes following
      infection.

PMID- 28499456
TI  - Role of microRNAs in premature ovarian insufficiency.
AB  - Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea lasting
      for a minimum of 4 months. The typical characteristics comprised of declined
      estrogen and raised serum concentrations of follicle-stimulating hormone (FSH) in
      women <40-year-old, primarily originating from iatrogenic factors, karyotypic
      abnormalities, and genetic factors. However, the etiology of POI remains unknown
      in approximately 90% of cases. POI could lead to infertility, osteoporosis,
      cardiovascular disorder, and cognitive dysfunction. MicroRNAs (miRNAs) are a
      class of endogenous noncoding RNAs (ncRNAs) that can mediate post-translational
      silencing of the genes involved in the regulation of proliferation,
      differentiation, apoptosis, development, tumorigenesis, and hematopoiesis.
      Recently, the regulatory functions of miRNAs in the development of POI have been
      the topic of intensive research. The present review addresses the association of
      miRNAs' machinery genes (Dicer, Drosha, and XPO5) with POI and the miRNA
      expression profiles in the plasma of patients with POI. In addition, several
      specific miRNAs (miR-23a, miR-27a, miR-22-3p, miR-146a, miR-196a, miR-290-295,
      miR-423, and miR-608) related to POI are also examined in order to highlight the
      issues that deserve further investigation. A thorough understanding of the exact
      regulatory roles of miRNAs is imperative to gain novel insights into the etiology
      of idiopathic POI and offer new research directions in the field.

PMID- 28499458
TI  - Evaluation of a Multilocus Sequence Typing (MLST) scheme for Leishmania (Viannia)
      braziliensis and Leishmania (Viannia) panamensis in Colombia.
AB  - BACKGROUND: Leishmaniases are parasitic vector-borne diseases affecting more than
      12 million people in 98 countries. In Colombia, leishmaniasis is widespread and
      the most common clinical manifestation is cutaneous, mainly caused by L.
      panamensis and L. braziliensis. Currently, the genetic diversity of these species
      in Colombia is unknown. To address this, we applied molecular techniques for
      their characterization, using multilocus sequence typing (MLST) to explore the
      genetic variability and phylodynamics of the disease. METHODS: Seven previously
      described genetic markers were selected highlighting the implementation of a
      mitochondrial marker. Markers were applied to 163 samples from isolates obtained
      between 1980 and 2001. RESULTS: The identification of the samples showed an
      excellent correlation with typing tests previously applied (MLEE, monoclonal
      antibodies). Isolates of L. braziliensis showed greater genetic diversity than L.
      panamensis, and a greater number of diploid sequence types (DSTs). In addition,
      the geographical distribution of DSTs for each species were obtained through
      georeferencing maps. CONCLUSIONS: To our knowldge, this study represents the
      first description of the genetic variability of L. panamensis in Colombia and
      South America, and is the first to propose a scheme of MLST for epidemiological
      surveillance of leishmaniasis in the country.

PMID- 28499457
TI  - Preconditioning of bone marrow-derived mesenchymal stromal cells by
      tetramethylpyrazine enhances cell migration and improves functional recovery
      after focal cerebral ischemia in rats.
AB  - BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs)
      is one of the new therapeutic strategies for treating ischemic stroke. However,
      the relatively poor migratory capacity of BMSCs toward infarcted regions limited
      the therapeutic potential of this approach. Pharmacological preconditioning can
      increase the expression of CXC chemokine receptor 4 (CXCR4) in BMSCs and enhance
      cell migration toward the injury site. In the present study, we investigated
      whether tetramethylpyrazine (TMP) preconditioning could enhance BMSCs migration
      to the ischemic brain and improve functional recovery through upregulating CXCR4
      expression. METHODS: BMSCs were identified by flow cytometry analysis. BMSCs
      migration was evaluated in vitro by transwell migration assay, and CXCR4
      expression was measured by quantitative reverse transcription-polymerase chain
      reaction and western blot analysis. In rats with focal cerebral ischemia, the
      neurological function was evaluated by the modified neurological severity score,
      the adhesive removal test and the corner test. The homing BMSCs and angiogenesis
      were detected by immunofluorescence, and expression of stromal cell-derived
      factor-1 (SDF-1) and CXCR4 was measured by western blot analysis. RESULTS: Flow
      cytometry analysis demonstrated that BMSCs expressed CD29 and CD90, but not CD34
      and CD45. TMP pretreatment dose-dependently induced BMSCs migration and CXCR4
      expression in vitro, which was significantly inhibited by AMD3100, a CXCR4
      antagonist. In rat stroke models, we found more TMP-preconditioned BMSCs homing
      toward the infarcted regions than nonpreconditioned cells, leading to improved
      neurological performance and enhanced angiogenesis. Moreover, TMP-preconditioned
      BMSCs significantly upregulated the protein expression of SDF-1 and CXCR4 in the
      ischemic boundary regions. These beneficial effects of TMP preconditioning were
      blocked by AMD3100. CONCLUSION: TMP preconditioning enhances the migration and
      homing ability of BMSCs, increases CXCR4 expression, promotes angiogenesis, and
      improves neurological performance. Therefore, TMP preconditioning may be an
      effective strategy to improve the therapeutic potency of BMSCs for ischemic
      stroke due to enhanced BMSCs migration to ischemic regions.

PMID- 28499460
TI  - The Euromelanoma Campaign.

PMID- 28499459
TI  - Dispatch and prehospital transport for acute septic patients: an observational
      study.
AB  - BACKGROUND: In order to dispatch ambulances with the correct level of urgency,
      the dispatch center has to balance the perceived urgency and traffic safety
      considerations with the available resources. As urgency is not clear in all
      clinical situations, some high urgency patients may end up with a suboptimal mode
      of transport. Patients with severe sepsis or septic shock suffer from highly time
      dependent conditions but they present with a wide range of symptoms, which might
      be difficult to identify in the dispatch system. The aim of the study is to
      investigate the modes of prehospital transport among acute admitted patients with
      sepsis, severe sepsis and septic shock. METHODS: We included all adult patients
      (>=15 years) presenting to an acute medical unit at Odense University Hospital
      with a first-time admission of community-acquired sepsis between September 2010
      August 2011. Cases and prehospital ambulance transport were identified by
      structured manual chart review. In all cases it was registered, whether the
      ordinary ambulance was assisted by the mobile emergency care unit (MECU), manned
      by anesthesiologists. RESULTS: We included 1,713 patients median age 72 years
      (IQR 57-81), 793 (46.3%) male, 621 (36.3%) had sepsis, 1,071 (62.5%) severe
      sepsis, and 21 (1.2%) septic shock. In the group of sepsis patients, 390 (62.8%)
      arrived without public prehospital transport, 197 (31.7%) were transported by
      ambulance, and 34 (5.5%) were assisted by MECU. In the group of severe sepsis
      patients, the same percentage 62.8% arrived without public pre-hospital
      transport, a lower percentage 28.2% were transported by ambulance, and a larger
      percentage 9.0% were transported by MECU. Among 21 patients with septic shock, 10
      arrived without public pre-hospital transport (47.7%), 7 (33.3%) were transported
      by ambulance, and 4 (19.0%) by MECU. The 30-day mortality hazard ratio was
      associated with mode of transport, with the adjusted highest hazard ratio found
      in the group of MECU transported patients 1.76 (95%Cl 1.16-2.66). CONCLUSIONS: A
      substantial proportion of patients with severe sepsis and septic shock arrive to
      hospital without public prehospital transport or by unspecialized ambulances.

PMID- 28499461
TI  - Nitric oxide: A possible new biomarker in heart failure? Relationship with
      pulmonary hypertension secondary to left heart failure.

PMID- 28499462
TI  - A stressful work environment is associated with tinnitus: Initial evidence from
      Asia.

PMID- 28499463
TI  - Diffusion control for a tempered anomalous diffusion system using fractional
      order PI controllers.
AB  - This paper is concerned with diffusion control problem of a tempered anomalous
      diffusion system based on fractional-order PI controllers. The contribution of
      this paper is to introduce fractional-order PI controllers into the tempered
      anomalous diffusion system for mobile actuators motion and spraying control. For
      the proposed control force, convergence analysis of the system described by
      mobile actuator dynamical equations is presented based on Lyapunov stability
      arguments. Moreover, a new Centroidal Voronoi Tessellation (CVT) algorithm based
      on fractional-order PI controllers, henceforth called FOPI-based CVT algorithm,
      is provided together with a modified simulation platform called Fractional-Order
      Diffusion Mobile Actuator-Sensor 2-Dimension Fractional-Order Proportional
      Integral (FO-Diff-MAS2D-FOPI). Finally, extensive numerical simulations for the
      tempered anomalous diffusion process are presented to verify the effectiveness of
      our proposed fractional-order PI controllers.

PMID- 28499464
TI  - Prospective study on ocular motility limitation due to orbital muscle entrapment
      or impingement associated with orbital wall fracture.
AB  - INTRODUCTION: The recommended urgent surgical management of ocular motility
      restriction due to orbital muscle entrapment or impingement associated with
      orbital wall fracture needs to be elucidated. AIM: To evaluate the importance of
      the time from injury to surgery for the outcome in ocular motility and diplopia,
      the time lapse of ocular motility, diplopia and hypesthesia recovery. MATERIAL
      AND METHODS: Patients with entrapment or impingement of orbital contents due to
      orbital wall fracture were followed up prospectively over 1year regarding ocular
      motility, diplopia, hypesthesia and cosmetic deformity. RESULTS: 21 patients (10
      entrapments and 11 impingements) were included and treated surgically. The median
      time from injury to surgery was 36 (8-413)h for the entrapment group and 168 (48
      326)h for the impingement group. The median time from study inclusion to surgery
      was 0 (0-1) days for the entrapment group and 1.0 (0.2-4.8) days for the
      impingement group. All the patients had ocular motility limitation and diplopia
      at the inclusion. Ocular motility improved gradually and was normal at final
      visit. Diplopia resolved gradually in all patients except in two with non
      disturbing diplopia, at the final visit. Forced duction test was positive in 90%
      of the patients in the entrapment group and 70% in impingement group. At final
      visit, hypesthesia was found in none of the patients in the entrapment group but
      in 4 patients in the impingement group. CONCLUSIONS: In this, the first
      prospective long term follow up of orbital wall fractures with ocular motility
      restriction, we did not find any significant correlation between the time from
      injury to surgery and the outcomes in ocular motility and diplopia. An entrapment
      requires surgery as soon as possible; however, the surgical reduction is at least
      as important as surgical timing. Surgery should be delayed until it can be
      performed by an experienced surgeon. Ocular motility restriction causing diplopia
      due to impingement is not an ophthalmologic emergency and surgery is recommended
      if the diplopia and ocular motility has not improved over time. Clinical
      examination of ocular motility and not CT scan findings is crucial to determine
      whether a limitation of ocular motility exists or not.

PMID- 28499465
TI  - Current treatment of infected non-union after intramedullary nailing.
AB  - Non-union is a devastating consequence of a fracture. Non-unions cause
      substantial patient morbidity with patients suffering from loss of function of
      the affected extremity, increased pain, and a substantial decrease in the quality
      of life. The management is often associated with repeated, unsuccessful
      operations resulting in prolonged hospital stays, which has social and economic
      consequences to both the patient and the healthcare system. The rates of non
      union following intramedullary (IM) nailing vary according to anatomical
      location. There is currently no consensus regarding the treatment of infected non
      unions following IM nailing, but the most common procedures reported are;
      exchange IM nail with antibiotic suppression or excision of the non-union,
      (stabilisation with external fixation or less commonly plate or IM nail) and then
      reconstruction of the bone defect with distraction osteogenesis or the Masquelet
      technique. This article explores the general principles of treatment, fixation
      modalities and proposes a treatment strategy for the management of infected non
      unions following intramedullary nailing.

PMID- 28499466
TI  - Technical considerations to avoid delayed and non-union.
AB  - For many years intramedullary nails have been a well accepted and successful
      method of diaphyseal fracture fixation. However, delayed and non unions with this
      technique do still occur and are associated with significant patient morbidity.
      The reason for this can be multi-factorial. We discuss a number of technical
      considerations to maximise fracture reduction, fracture stability and fracture
      vascularity in order to achieve bony union.

PMID- 28499468
TI  - Corrigendum to "Ultrasensitive and selective electrochemical biosensor for
      detection of mercury (II) ions by nicking endonuclease-assisted target recycling
      and hybridization chain reaction signal amplification" [Biosens. Bioelectron. 94
      (2017) 19-23].

PMID- 28499467
TI  - Secondary sinus lift: a viable option to increase contact of bone to implant.

PMID- 28499469
TI  - Phylogenetically diverse groups of Bradyrhizobium isolated from nodules of tree
      and annual legume species growing in Ethiopia.
AB  - Bacteria belonging to the genus Bradyrhizobium nodulate various leguminous woody
      plants and herbs, including economically important crops such as soybean, peanut
      and cowpea. Here we analysed 39 Bradyrhizobium strains originating from root
      nodules of the leguminous trees and crops Acacia saligna, Faidherbia albida,
      Erythrina brucei, Albizia gummifera, Millettia ferruginea, Cajanus cajan, Vigna
      unguiculata and Phaseolus vulgaris, growing in southern Ethiopia. Multilocus
      sequence analyses (MLSA) of the 16S rRNA, glnII, recA, gyrB and dnaK genes and
      the ITS region grouped the test strains into seven well-supported genospecies (I
      VII), six of which occupied distinct positions excluding all hitherto defined
      Bradyrhizobium species. Analyses of the nodA, nodC and nifH genes suggested
      different evolutionary history of the chromosomal and symbiosis-related genes.
      Our study corroborates earlier findings that Ethiopia is a hotspot for rhizobial
      biodiversity, justifying further search for novel strains from this region and
      calling for intensified research on the ecology and biochemistry of these
      organisms.

PMID- 28499470
TI  - Exercise and environment: New qualitative work to link popular practice and
      public health.
AB  - The health benefits of physical activity are many and well known. Those hoping to
      promote public health are therefore understandably keen on encouraging physical
      exercise. This commentary considers the role of qualitative research in this
      undertaking, given a context in which medical researchers have more commonly
      taken a quantitative approach to the motivations that are thought to underpin
      exercise. Our core argument is that studies concerned with how particular
      environments are inhabited by particular groups of exercisers could play a more
      central part in public health promotion. In making this case, and by way of an
      introduction to this Health and Place special issue, we present a series of
      statements that we think could usefully guide the further development of this
      work. Specifically, we argue for further attention to: the ways in which
      different material settings play into the exercise experience; how many of the
      exercise practices that we may hope to understand sit rather uneasily with the
      idea of sport; the subtleties of how sociality features in contemporary exercise
      practices; the physical pleasures that come from exercise; and how exercise
      practices are both acquired by individuals and evolve as a whole. In so doing,
      the aim is to encourage relevant researchers to engage more directly in
      conversation with health promoters instead of either being indifferent to, or
      critical of, them.

PMID- 28499472
TI  - ?

PMID- 28499471
TI  - Cytoskeletal connectivity may guide erythrocyte membrane ex- and invagination - A
      discussion point how biophysical principles might be exploited by a parasite
      invading erythrocytes.

PMID- 28499473
TI  - [Child protection, a question of society].
AB  - Child protection is a sector undergoing major changes in which local authorities
      play a central role. There are several different types of child protection
      measures covering different needs: monitoring in the home, foster family,
      placement in a children's home or a stay in a mother-and-baby centre for young
      mothers. For all these children and adolescents, leaving care is a key moment
      which requires support.

PMID- 28499474
TI  - [Legislative evolution and regulatory framework of child placement].
AB  - In the area of child protection, French law has evolved considerably over recent
      decades. Leal texts provide the system with a very precise structure, in order to
      organise child protection on an administrative and judicial level.

PMID- 28499475
TI  - [Clinical application of attachment].
AB  - By favouring the proximity of a caregiver, attachment is essential for enabling
      children to live and grow. It constitutes both an emotion regulator and an
      internal security base. It is a complex process which evolves throughout a
      person's lifetime.

PMID- 28499476
TI  - ["Operation pouponnieres", yesterday and today: placement or a living
      environment?]
AB  - For several decades, major progress has been made in changing and improving
      living conditions for children placed in an infant care home. From hospitalism to
      the emergence of the concept of compassionate care, professionals have constantly
      striven to support this evolution.

PMID- 28499477
TI  - [Placement, a therapeutic act].
AB  - Any proposed placement of a child is carried out with the aim of providing
      protection as well as care. The therapeutic aspect is not straightforward, as it
      comes up against the repetition of situations, the anxiety and the defences of
      all concerned. In these complex situations, it is essential to provide suitable
      care to the child and their parents.

PMID- 28499478
TI  - [The nurse and child health nurse at the heart of the care in an infant care
      home].
AB  - Infant care homes cater for children up to the age of 3. The work of the nurse
      and the child health nurse lies at the heart of the care project, helping the
      children to construct themselves and develop. The harmonisation of practices and
      continuity are essential notions.

PMID- 28499480
TI  - [The place of the parents in an infant care home].
AB  - In the infant unit of Chambery children's home, the organisation of parental
      visits is the fruit of an institutional project. Practices have changed over the
      years. The reflection and the responsiveness of the professionals and their
      desire to create a secure environment for the children and the parents, have
      enabled them to establish a setting which favours the preservation of the parent
      child bond.

PMID- 28499479
TI  - [Different perspectives on caring for a child in an infant care home].
AB  - Caring for a child in an infant care home leads professionals to examine their
      practices. Perrine Hugel, manager of an infant care home, and Maud Leon, an
      auxiliary child health nurse in the same home, describes the nursing values which
      they implement on a daily basis to favour the wellbeing of the infant and support
      parenthood.

PMID- 28499481
TI  - [Supporting the parental function in the case of child placement].
AB  - When a child is placed in care, it is important that the parents' access visit
      can take place in an environment which helps to support the parental function.
      Time remains a major component which professionals must understand in order to
      support the children and their parents along this long pathway. This article
      presents the experience of the Diapason service, a meeting place for parents of
      children in care.

PMID- 28499482
TI  - [A scheme to support teenagers in care].
AB  - In some family situations, the placement of a teenager, even in the case of a
      court decision, proves ineffective. The accumulation of all kinds of difficulties
      requires a different type of support, based on responsiveness, attention and
      above all time to come together. A dedicated scheme helps to prevent situations
      of waywardness or marginalisation among these teenagers and to support the
      families.

PMID- 28499483
TI  - ["An adopted family for Katherina"].
AB  - A foster mother took into her home Katherina, a 5-month-old girl placed by the
      child welfare services. Before taking the decision, she discussed it with her
      partner and her own children. Straight after Katherina's arrival, visits were
      organised in order to maintain, as much as possible, the child's bond with her
      mother.

PMID- 28499484
TI  - [Adverse events in neonatology, contribution of a standardised register].
AB  - Despite the recommendation to report all adverse events to the risk management
      unit, such reporting is far from consistent. An internal, standardised register
      of adverse events, was put in place in a neonatology unit for six months. An
      analysis of the reports has led to the reorganisation of the unit and practices
      as part of a drive to improve the quality of care.

PMID- 28499485
TI  - ?

PMID- 28499486
TI  - Intra-osseous local anaesthetic patellar pain catheter suppresses osteoarthritic
      patello-femoral pain.
AB  - BACKGROUND: The source of pain in patellofemoral osteoarthritis is not fully
      understood. The purpose of this study was to identify the origin of pain using
      intraosseous pain catheters and to show early results with an osteotomy that is
      potentially denervating and hydrostatic pressure-relieving. METHODS: Five
      patients with patellofemoral osteoarthritis and pain with straight downward
      patellofemoral compression were included. All underwent arthroscopic placement of
      two 0.8mm catheters into the medial and lateral patella prior to subsequent
      patellar facetectomy with an incomplete horizontal patellar osteotomy. The
      catheters were first flushed with 0.5ml saline, then with local anaesthetic to
      determine pain response. After a mean of 44months the latest clinical examination
      was performed. RESULTS: Instillation of less than 0.5ml of saline provoked sharp
      pain, which could be localised by all patients as medial or lateral within the
      patella. Subsequent instillation of local anaesthetic suppressed the mean
      patellar tenderness during axial compression from VAS 6 to VAS 1. In one of the
      five patients, patellar osteotomy did not relieve symptoms and further surgical
      intervention was required. The remaining four patients experienced a clinical
      improvement with a mean subjective knee value of 55 (range 40 to 65) out of 100.
      CONCLUSION: This is the first report on intraosseous catheters applying local
      anaesthetics into bone. There is a surprisingly precise intraosseous spatial
      resolution of pain perception in the patella and triggering of pain in
      osteoarthritis appears at least in part to occur through intraosseous increase of
      hydrostatic pressure. LEVEL OF EVIDENCE: Level IV, Case Series.

PMID- 28499487
TI  - External beam radiation therapy with or without low-dose-rate brachytherapy:
      Analysis of favorable and unfavorable intermediate-risk prostate cancer patients.
AB  - PURPOSE: To compare the tumor control and toxicity in men with intermediate-risk
      prostate cancer treated with either external beam radiation therapy (EBRT) or
      EBRT plus low-dose-rate brachytherapy (combo-RT). METHODS AND MATERIALS: Between
      1995 and 2012, 579 men with intermediate-risk prostate cancer were treated with
      either EBRT (n = 388) or combo-RT (n = 191). Outcomes assessed included
      biochemical recurrence-free survival (bRFS), distant metastasis-free survival
      (DMFS), and cumulative incidence of genitourinary (GU) and gastrointestinal
      toxicity. Favorable and unfavorable intermediate-risk subgroups were analyzed.
      RESULTS: Median followup was 7.5 years. Combo-RT group had improved 10-year bRFS
      compared with EBRT (91.7% vs. 75.4%, p = 0.014). On multivariable analysis, combo
      RT (hazard ratio, 0.48; 95% confidence interval: 0.25, 0.92; p = 0.03) was
      associated with improved bRFS. Combo-RT had significantly improved bRFS compared
      with EBRT in the unfavorable subgroup (p = 0.02) but not in the favorable
      subgroup (p = 0.37). DMFS was similar within the entire cohort and by risk group.
      Combo-RT was associated with an increased rate in the 6-year cumulative incidence
      of Grade 3 GU toxicity (hazard ratio, 3.48; 95% confidence interval: 1.1, 11.1; p
      = 0.026); however, 57% of Grade 3 GU toxicity was resolved, 29% had partial
      improvement, and only 1 patient had persistent Grade 3 GU toxicity. CONCLUSIONS:
      In intermediate-risk prostate cancer, combo-RT improved bRFS but not DMFS and
      increased Grade 3 GU toxicity. The bRFS benefit was limited to unfavorable
      intermediate-risk patients.

PMID- 28499488
TI  - In vivo dosimetry with alanine/electron spin resonance dosimetry to evaluate the
      urethra dose during high-dose-rate brachytherapy.
AB  - PURPOSE: To determine the dose of the urethra during Ir-192 high-dose-rate
      brachytherapy in 15 patients, a new detector form developed for in vivo
      measurements was used as described by Anton et al. 2009. METHODS AND MATERIALS:
      The detector consists of alanine powder with paraffin as binder which was filled
      in a shrinkable tube for measurements. The alanine strand so produced was
      inserted in the foley catheter during high-dose-rate brachytherapy of the
      prostate. The measured dose was compared with the dose calculated by the
      treatment planning system SWIFT for 15 patients. After 8 patients, a marker was
      introduced for better positioning of the alanine strand using transrectal
      ultrasound images. RESULTS: The measurements of the dose of the urethra agreed
      very well with the dose calculated by SWIFT within the estimated standard
      uncertainty of the method for 8 patients with a mean absolute deviation of 0.08
      Gy. However, for the other 7 patients, a mean absolute deviation between
      delivered and measured dose of -5.13 Gy was seen. For these patients, the active
      volume of the alanine dosimeter could not properly be reconstructed on the
      ultrasound images. CONCLUSION: The method presented in this study is useful for
      quality control of irradiations in vivo. To reconstruct the active volume on the
      corresponding ultrasound images, the correct application of the alanine strand in
      the urethra is very important. This procedure needs a well-trained physician.

PMID- 28499489
TI  - Neuronal PAS Domain Proteins 1 and 3 Are Master Regulators of Neuropsychiatric
      Risk Genes.
AB  - BACKGROUND: NPAS3 has been established as a robust genetic risk factor in major
      mental illness. In mice, loss of neuronal PAS domain protein 3 (NPAS3) impairs
      postnatal hippocampal neurogenesis, while loss of the related protein NPAS1
      promotes it. These and other findings suggest a critical role for NPAS proteins
      in neuropsychiatric functioning, prompting interest in the molecular pathways
      under their control. METHODS: We used RNA sequencing coupled with chromatin
      immunoprecipitation sequencing to identify genes directly regulated by NPAS1 and
      NPAS3 in the hippocampus of wild-type, Npas1-/-, and Npas3-/- mice. Computational
      integration with human genetic and expression data revealed the disease relevance
      of NPAS-regulated genes and pathways. Specific findings were confirmed at the
      protein level by Western blot. RESULTS: This is the first in vivo, transcriptome
      scale investigation of genes regulated by NPAS1 and NPAS3. These transcription
      factors control an ensemble of genes that are themselves also major regulators of
      neuropsychiatric function. Specifically, Fmr1 (fragile X syndrome) and Ube3a
      (Angelman syndrome) are transcriptionally regulated by NPAS3, as is the
      neurogenesis regulator Notch. Dysregulation of these pathways was confirmed at
      the protein level. Furthermore, NPAS1/3 targets show increased human genetic
      burden for schizophrenia and intellectual disability. CONCLUSIONS: Together,
      these data provide a clear, unbiased view of the full spectrum of genes regulated
      by NPAS1 and NPAS3 and show that these transcription factors are master
      regulators of neuropsychiatric function. These findings expose the molecular
      pathophysiology of NPAS1/3 mutations and provide a striking example of the
      shared, combinatorial nature of molecular pathways that underlie diagnostically
      distinct neuropsychiatric conditions.

PMID- 28499490
TI  - Frequent inoculations with radiation attenuated sporozoite is essential for
      inducing sterile protection that correlates with a threshold level of Plasmodia
      liver-stage specific CD8+ T cells.
AB  - Whole sporozoite vaccine (WSV) is shown to induce sterile protection that targets
      Plasmodium liver-stage infection. There are many underlying issues associated
      with induction of effective sterile protracted protection. In this study, we have
      addressed how the alterations in successive vaccine regimen could possibly affect
      the induction of sterile protection. We have demonstrated that the pattern of
      vaccination with RAS (radiation attenuated sporozoites) induces varying degrees
      of protection among B6 mice. Animals receiving four successive doses generated
      100% sterile protection. However, three successive doses, though with the same
      parasite inoculum as four doses, could induce sterile protection in ~50% mice.
      Interestingly, mice immunized with the same 3 doses, but with longer gap, could
      not survive the challenge. We demonstrate that degree of protection correlates
      with the frequencies of IFN-gamma+ and multifunctional (IFN-gamma+ CD107a+) CD8+
      TEM cells present in liver. The failure to achieve protective threshold frequency
      of these cells in liver might make the host more vulnerable to parasite infection
      during infectious sporozoite challenge.

PMID- 28499492
TI  - Mechanisms and Dynamics of T Cell-Mediated Cytotoxicity In Vivo.
AB  - Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or
      malignant cells and are emerging as a major therapeutic target. How CTLs
      recognize and kill harmful cells has been characterized in vitro but little is
      known about these processes in the living organism. Here we review recent
      insights into CTL-mediated killing with an emphasis on in vivo CTL biology.
      Specifically, we focus on the possible rate-limiting steps determining the
      efficiency of CTL-mediated killing. We also highlight the need for cell-based
      datasets that permit the quantification of CTL dynamics, including CTL location,
      migration, and killing rates. A better understanding of these factors is required
      to predict protective CD8 T cell immunity in vivo and to design optimized
      vaccination protocols.

PMID- 28499493
TI  - Bifunctional dentifrice: Amorphous polyphosphate a regeneratively active sealant
      with potent anti-Streptococcus mutans activity.
AB  - OBJECTIVE: In this study we demonstrate that inorganic polyphosphate (polyP)
      exhibits a dual protective effect on teeth: it elicits a strong antibacterial
      effect against the cariogenic bacterium Streptococcus mutans and, in form of
      amorphous calcium polyP microparticles (size of 100-400nm), it efficiently
      reseals cracks/fissures in the tooth enamel and dentin. METHODS: Three different
      formulations of amorphous polyP microparticles (Ca-polyP, Zn-polyP and Sr-polyP)
      were prepared. RESULTS: Among the different polyP microparticles tested, the Ca
      polyP microparticles, as a component of a newly developed formulation of a
      dentifrice, turned out to be most effective in inhibiting growth of S. mutans.
      Further studies have shown that it is mainly the soluble polyP, which has a
      strong antibacterial activity, either given as sodium salt of polyP or formed by
      partial disintegration of the microparticles via the alkaline phosphatase present
      in the oropharyngeal cavity. In addition, we demonstrate that the developed
      toothpaste containing incorporated amorphous polyP microparticles, efficiently
      reduces dental biofilm formation. SIGNIFICANCE: From our results we conclude that
      polyP microparticles, if added to toothpaste in an amorphous state, might be
      beneficial not only for restoring tooth damages but also because they provide a
      suitable depot of functionally/antibacterially active soluble polyP.

PMID- 28499494
TI  - Corrigendum to "Take a look at the bright side: Effects of positive body exposure
      on selective visual attention in women with high body dissatisfaction" [Behav.
      Res. Therapy 83 (2016) 19-25].

PMID- 28499495
TI  - Distraction/Suppression and Distress Endurance diminish the extent to which
      generalized conditioned fear is associated with maladaptive behavioral avoidance.
AB  - A central conditioning correlate of clinical anxiety is the over-generalization
      of Pavlovian fear to safe stimuli resembling conditioned danger cues (CS+).
      Though much of the pathogenic influence of such generalization may lie in the
      unnecessary behavioral avoidance it evokes, few studies have examined maladaptive
      avoidance associated with Pavlovian generalization. Lab-based assessments of this
      process, here referred to as instrumental avoidance from Pavlovian generalization
      (IAP-G), have recently begun. The current study represents a next step in this
      line of work by examining personality factors that may reduce maladaptive IAP-G.
      This is a clinically relevant effort, as such traits may reflect resilience
      factors, with high levels reducing the likelihood of maladaptive generalized
      avoidance following Pavlovian generalization. Here we focus on the effects of
      Distraction/Suppression (DS) and Distress Endurance (DE) on IAP-G. Results
      indicate that both DS and DE moderate IAP-G by weakening relations between
      Pavlovian generalization of fear-potentiated startle and maladaptive generalized
      avoidance. Further, moderating effects of DS were most pronounced for more
      ambiguous cues of threat (i.e., stimuli moderately resembling CS+), while
      moderating effects of DE were most pronounced for more certain cues of threat
      (i.e., stimuli highly resembling CS+, as well as the CS + itself). Results
      implicate DS and DE as protective factors against the maladaptive behavioral
      consequences of Pavlovian generalization, and further indicate that the
      protective influence of these traits may depend on the ambiguity of the threat at
      hand.

PMID- 28499496
TI  - Relationships Between Quantitative Pulse-Echo Ultrasound Parameters from the
      Superficial Zone of the Human Articular Cartilage and Changes in Surface
      Roughness, Collagen Content or Collagen Orientation Caused by Early Degeneration.
AB  - We aimed to quantitatively investigate the relationship between amplitude-based
      pulse-echo ultrasound parameters and early degeneration of the knee articular
      cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1
      according to International Cartilage Repair Society grading were assessed using a
      15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (Rq),
      average collagen content (A1) and collagen orientation (A12) in the superficial
      zone of the cartilage were measured via laser microscopy and Fourier transform
      infrared imaging spectroscopy. Multiple regression analysis with a linear mixed
      effects model (LMM) revealed that a time-domain reflection coefficient at the
      cartilage surface (Rc) had a significant coefficient of determination with Rq and
      A12 (RLMMm2=0.79); however, Rc did not correlate with A1. Concerning the collagen
      characteristic in the superficial zone, Rc was found to be a sensitive indicator
      reflecting collagen disorganization, not collagen content, for the early
      degeneration samples.

PMID- 28499497
TI  - A sensitive chemiluminescence enzyme immunoassay based on molecularly imprinted
      polymers solid-phase extraction of parathion.
AB  - The chemiluminescence enzyme immunoassay (CLEIA) method responds differently to
      various sample matrices because of the matrix effect. In this work, the CLEIA
      method was coupled with molecularly imprinted polymers (MIPs) synthesized by
      precipitation polymerization to study the matrix effect. The sample recoveries
      ranged from 72.62% to 121.89%, with a relative standard deviation (RSD) of 3.74
      18.14%.The ratio of the sample matrix-matched standard curve slope rate to the
      solvent standard curve slope was 1.21, 1.12, 1.17, and 0.85 for apple, rice,
      orange and cabbage in samples pretreated with the mixture of PSA and C18.
      However, the ratio of sample (apple, rice, orange, and cabbage) matrix-matched
      standard-MIPs curve slope rate to the solvent standard curve was 1.05, 0.92,
      1.09, and 1.05 in samples pretreated with MIPs, respectively. The results
      demonstrated that the matrices of the samples greatly interfered with the
      detection of parathion residues by CLEIA. The MIPs bound specifically to the
      parathion in the samples and eliminated the matrix interference effect.
      Therefore, the CLEIA method have successfully applied MIPs in sample pretreatment
      to eliminate matrix interference effects and provided a new sensitive assay for
      agro-products.

PMID- 28499498
TI  - Aptatope mapping of the binding site of a progesterone aptamer on the steroid
      ring structure.
AB  - In this work we report the mapping of the binding site of the only progesterone
      aptamer published to date, in an approach referred to as aptatope mapping. By
      linking the binding data obtained from microscale thermophoresis analysis to the
      structural differences on the ring structure of a range of steroids, we
      elucidated the moieties involved in aptamer-progesterone binding. This approach
      can be further exploited for the characterization of aptamer specificity and
      ultimately facilitate the development of aptamer-based assays depending on the
      desired specificity.

PMID- 28499499
TI  - Heat-related morbidity and mortality in New England: Evidence for local policy.
AB  - BACKGROUND: Heat-related morbidity and mortality is a recognized public health
      concern. However, public health officials need to base policy decisions on local
      evidence, which is often lacking for smaller communities. OBJECTIVES: To evaluate
      the association between maximum daily heat index (HI) and morbidity and mortality
      in 15 New England communities (combined population: 2.7 million) in order to
      provide actionable evidence for local officials. METHODS: We applied
      overdispersed Poisson nonlinear distributed lag models to evaluate the
      association between HI and daily (May-September) emergency department (ED)
      admissions and deaths in each of 15 study sites in New Hampshire, Maine, and
      Rhode Island, controlling for time trends, day of week, and federal holidays.
      Site-specific estimates were meta-analyzed to provide regional estimates.
      RESULTS: Associations (sometimes non-linear) were observed between HI and each
      health outcome. For example, a day with a HI of 95 degrees F vs. 75 degrees F was
      associated with a cumulative 7.5% (95% confidence interval [CI]: 6.5%, 8.5%) and
      5.1% (95% CI: 0.2%, 10.3%) higher rate of all-cause ED visits and deaths,
      respectively, with some evidence of regional heterogeneity. We estimate that in
      the study area, days with a HI>=95 degrees F were associated with an annual
      average of 784 (95% CI: 658, 908) excess ED visits and 22 (95% CI: 3, 39) excess
      deaths. CONCLUSIONS: Our results suggest the presence of adverse health impacts
      associated with HI below the current local guideline criteria of HI>=100 degrees
      F used to issue heat advisories. We hypothesize that lowering this threshold may
      lead to substantially reduced heat-related morbidity and mortality in the study
      area.

PMID- 28499500
TI  - Ca2+ Release Channels Join the 'Resolution Revolution'.
AB  - Ryanodine receptors (RyRs) are calcium release channels expressed in the
      sarcoendoplasmic reticula of many cell types including cardiac and skeletal
      muscle cells. In recent years Ca2+ leak through RyRs has been implicated as a
      major contributor to the development of diseases including heart failure, muscle
      myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic
      target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of
      multiple functional states have clarified longstanding questions including the
      architecture of the transmembrane (TM) pore and cytoplasmic domains, the location
      and architecture of the channel gate, ligand-binding sites, and the gating
      mechanism. As we advance toward complete models of RyRs this new information
      enables the determination of domain-domain interfaces and the location and
      structural effects of disease-causing RyR mutations.

PMID- 28499501
TI  - Potential involvement of chondroitin sulfate A in the pathogenesis of
      ameloblastoma.
AB  - Ameloblastoma is classified as a benign odontogenic tumor characterized by
      locally invasive behavior and high risk of recurrence. Here, we evaluate a
      potential role for glycosaminoglycan, a structural component of cell membranes
      and extracellular matrix, in ameloblstoma pathogenesis. We subjected formalin
      fixed, paraffin-embedded tissue sections of 34 cases of ameloblastoma, 10 of
      odontogenic keratocyst, and 17 of dentigerous cyst to immunohistochemistry using
      monoclonal antibodies recognizing chondroitin sulfate A (CS-A), heparan sulfate
      (HS), and keratan sulfate (KS). Expression levels of CS-A in epithelial component
      and stroma of ameloblastoma were significantly higher than those in odontogenic
      keratocyst and dentigerous cyst. Moreover, CS-A in ameloblastoma was more
      strongly expressed in stellate reticulum-like cells than in amelobast-like cells
      with statistical significance. On the other hand, expression levels of HS and KS
      in epithelial component and stroma of ameloblastoma were lower compared with CS
      A. These results overall reveal that among these odontogenic lesions, CS-A is
      preferentially expessed in ameloblastoma, suggesting potential pathogenetic role
      probably in cytodifferention of tumor cells to stellate reticulum-like cells.

PMID- 28499502
TI  - Sesamin encouraging effects on chondrogenic differentiation of human amniotic
      fluid-derived mesenchymal stem cells.
AB  - Worldwide, the most recognized musculoskeletal degenerative disease is
      osteoarthritis (OA). Sesamin, a major abundant lignan compound present in Sesamun
      Indicum Linn, has been described for its various pharmacological effects and
      health benefits. However, the promoting effects of sesamin on chondrogenic
      differentiation have not yet been observed. Herein, the aim of this study was to
      investigate the effects of sesamin on cell cytotoxicity and the potent supporting
      effects on chondrogenic differentiation of human amniotic fluid-derived
      mesenchymal stem cells (hAF-MSCs). The results indicated that sesamin was not
      toxic to hAF-MSCs after sesamin treatment. When treating the cells with a
      combination of sesamin and inducing factors, sesamin was able to up-regulate the
      expression level of specific genes which play an essential role during the
      cartilage development process, including SOX9, AGC, COL2A1, COL11A1, and COMP and
      also simultaneously promote the cartilage extracellular protein synthesis,
      aggrecan and type II collagen. Additionally, histological analysis revealed a
      high amount of accumulated sGAG staining inside the porous scaffold in the
      sesamin co-treating group. In conclusion, the results of this study have
      indicated that sesamin can be considered a chondrogenic inducing factor and a
      beneficial dietary supplement for cartilage repair.

PMID- 28499503
TI  - Mast cells in neuroinflammation and brain disorders.
AB  - It is well recognized that neuroinflammation is involved in the pathogenesis of
      various neurodegenerative diseases. Microglia and astrocytes are major pathogenic
      components within this process and known to respond to proinflammatory mediators
      released from immune cells such as mast cells. Mast cells reside in the brain and
      are an important source of inflammatory molecules. Mast cell interactions with
      glial cells and neurons result in the release of mediators such as cytokines,
      proteases and reactive oxygen species. During neuroinflammation, excessive levels
      of these mediators can influence neurogenesis, neurodegeneration and blood-brain
      barrier (BBB) permeability. Mast cells are considered first responders and are
      able to initiate and magnify immune responses in the brain. Their possible role
      in neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease
      and autism has gained increasing interest. We discuss the possible involvement of
      mast cells and their mediators in neurogenesis, neurodegeneration and BBB
      permeability and their role in neuronal disorders such as cerebral ischemia,
      traumatic brain injury, neuropathic pain, multiple sclerosis, Alzheimer's
      disease, migraine, autism, and depression.

PMID- 28499504
TI  - Williams syndrome deletions and duplications: Genetic windows to understanding
      anxiety, sociality, autism, and schizophrenia.
AB  - We describe and evaluate an integrative hypothesis for helping to explain the
      major neurocognitive features of individuals with Williams syndrome region
      deletions and duplications. First, we demonstrate how the cognitive differences
      between Williams syndrome individuals, individuals with duplications of this
      region, and healthy individuals parallel the differences between individuals
      subject to effects of increased or decreased oxytocin. Second, we synthesize
      evidence showing that variation in expression of the gene GTF2I (General
      Transcription Factor II-I) underlies the primary social phenotypes of Williams
      syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity,
      and its correlates, in healthy populations. Third, we describe findings relevant
      to the hypothesis that the GTF2I gene is subject to parent of origin effects
      whose behavioral expression fits with predictions from the kinship theory of
      genomic imprinting. Fourth, we describe how Williams syndrome can be considered,
      in part, as an autistic syndrome of Lorna Wing's 'active-but-odd' autism subtype,
      in contrast to associations of duplications with both schizophrenia and autism.

PMID- 28499505
TI  - Multiple central giant cell tumour lesions are exclusively linked to syndromes
      related to RAS/MAPK pathway anomalies.

PMID- 28499506
TI  - Influence of implant location in patients with and without type 2 diabetes
      mellitus: 2-year follow-up.
AB  - The aim of the present cross-sectional retrospective 2-year follow-up clinical
      study was to assess the influence of implant location on clinical and
      radiographic parameters around dental implants placed in patients with and
      without type 2 diabetes mellitus (T2DM). Twenty-seven patients with T2DM and 25
      non-diabetic controls were included. Implants were classified into three zones
      according to their location: (1) anterior zone: implant/s replacing anterior
      teeth, (2) middle zone: implant/s replacing premolars, and (3) posterior zone:
      implant/s replacing molars. Peri-implant bleeding on probing (BOP), probing depth
      (PD), and crestal bone loss (CBL) were measured. P-values less than 0.05 were
      considered statistically significant. The mean age of patients with T2DM was 42.5
      years and that of non-diabetic controls was 40.6 years. The mean fasting blood
      glucose levels of patients with and without T2DM were 74.5mg/dl (66-80mg/dl) and
      82.5mg/dl (79-88.1mg/dl), respectively. The mean duration of T2DM was 4.3 years.
      There was no significant difference in BOP, PD, or CBL around implants placed in
      any of the zones in the jaws of patients with and without T2DM. There is no
      influence of implant location on clinical and radiographic parameters around
      dental implants placed in patients with and without T2DM.

PMID- 28499507
TI  - Nasolabial changes after two different approaches for surgically assisted rapid
      maxillary expansion.
AB  - This retrospective study evaluated the nasolabial changes in patients who
      underwent surgically assisted rapid maxillary expansion (SARME) using two
      different approaches. Nineteen patients were included in the study, divided into
      two groups according to the kind of surgical approach performed: group 1 (n=9),
      SARME performed through the standard Le Fort I circumvestibular approach followed
      by the alar base cinch, and group 2 (n=10), SARME performed through a subtotal
      vestibular approach associated to a V-shaped incision at the maxillary midline in
      the labial frenulum region, without alar base cinch. Measurements of width,
      length, and nasal projection as well as upper lip length were taken from cone
      beam tomographic images obtained before surgery (T1) and 6 months postoperatively
      (T2). Both groups presented an increase in the alar base width postoperatively
      (P<0.05). The approach used in group 2 resulted in smaller changes in the alar
      base width as measured at the superior alar curvature (P<0.05). Nasal length and
      projection and upper lip length were not altered by SARME. The type of surgical
      approach influenced nasolabial changes, but did not eliminate increase in width
      of the alar base.

PMID- 28499508
TI  - New approach to establish an object reference frame for dental arch in computer
      aided surgical simulation.
AB  - The purpose of this study was to develop a principal component analysis-based
      adaptive minimum Euclidean distances (PAMED) approach to establish an optimal
      object reference frame for symmetrical alignment of the dental arch during
      computer-aided surgical simulation (CASS). It was compared with our triangular
      methods and the standard principal component analysis (PCA) method. Thirty sets
      of maxillary digital models were used. Midsagittal and occlusal planes were
      ranked by three experienced evaluators based on their clinical judgment. The
      results showed that for the midsagittal plane, all three evaluators ranked
      "ideal" for all 30 models with the PAMED method, 28 with the triangular method,
      and at least 11 with the PCA method. For the occlusal plane, one evaluator ranked
      all 30 models "ideal" with both the PAMED and the PCA methods while the other two
      evaluators ranked all 30 models "ideal" with the triangular method. However, the
      differences among the three methods were minimal. In conclusion, our PAMED method
      is the most reliable and consistent approach for establishing the object
      reference frame for the dental arch in orthognathic surgical planning. The
      triangular method should be used with caution because it can be affected by
      dental arch asymmetry. The standard PCA method is not recommended.

PMID- 28499509
TI  - Ten-year study of postoperative complications following dental extractions in
      patients with inherited bleeding disorders.
AB  - Dental extractions challenge the body's haemostatic mechanism. Postoperative
      bleeding from dental extraction can be prolonged, or even life threatening in
      patients with inherited bleeding disorders. Pre- and postoperative clotting
      factor replacements or systemic desmopressin (ddAVP) have been advocated at our
      institution to prevent bleeding complications in these patients. This study aimed
      to assess the postoperative bleeding rate in patients with inherited bleeding
      disorders that underwent dental extractions at our institution between 2003 and
      2012. Patients with inherited bleeding disorders such as haemophilia A,
      haemophilia B, and von Willebrand's disease were included. Retrospective chart
      review was conducted. The result showed 53 extraction events occurred in 45
      patients over the 10-year period. Ten out of 53 extraction events (18.9%) had
      postoperative bleeding requiring further factor replacement or ddAVP.
      Postoperative bleeding in one patient with mild haemophilia A was complicated by
      the development of inhibitors. Type and severity of bleeding disorder, bone
      removal, and use of a local haemostatic agent did not have any significant effect
      on postoperative bleeding. Despite the use of perioperative factors and
      desmopressin, the postoperative bleeding rates remain high for patients with
      inherited bleeding disorders. More studies are required to assess the safety and
      effectiveness of using local haemostatic control to achieve haemostasis following
      extractions.

PMID- 28499511
TI  - 73-Year-Old Asymptomatic Woman With Anemia.

PMID- 28499510
TI  - Effect of Policy Change on the Use of Long-Distance Transport and Follow-Up Care
      for Patients With Traumatic Finger Amputations.
AB  - PURPOSE: In January 2006, the American College of Emergency Physicians released
      updated guidelines for air transfer. Digit amputation and near-amputation were no
      longer an indication for this costly service. We analyzed the effect of this
      update on the use of air transport and associated care outcomes for finger
      amputation patients and examined factors involved in providing follow-up care for
      these patients. METHODS: A retrospective chart review identified all patients
      treated for traumatic finger amputation between 1995 and 2012 at a major hand
      trauma referral center. Analysis of available outcome measures was conducted
      using multiple logistic and linear regression models. Analysis of factors
      affecting frequency of return visits was performed via negative binomial
      regression. RESULTS: We identified 724 patients with isolated traumatic finger
      amputations. A total of 267 patients (37%) were transferred from an outside
      hospital. Patients injured after 2006 were less likely to be transferred via air,
      with a decrease from 29.5% pre-2006 to 14.9% post-2006. There was no difference
      in likelihood of replantation success, length of hospital stay, or number of
      return visits pre- versus post-2006. Patients transferred via helicopter after
      2006 were more likely to be younger than 20 years of age and injured in a winter
      month. Following successful replantation, work-relatedness was associated with a
      higher number of return visits, whereas increasing age and transfer from farther
      than 100 miles away were associated with fewer. CONCLUSIONS: After the American
      College of Emergency Physicians policy update, decreased use of emergency air
      transport to a hand trauma referral center for patients with traumatic finger
      amputations did not adversely affect care delivery and outcomes. These changes
      may be successfully implemented on a center-by-center basis to reduce costs
      without detriment to patient care; however, coordination of follow-up care for
      long-distance transport patients may require special focus when designing policy
      around referral centers. TYPE PF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 28499512
TI  - The Organ Transplant Imperative.
AB  - More than 120,000 US patients were listed for solid organ transplants in 2016.
      Although data are scarce, we suspect that many of these patients will die while
      awaiting transplant and without engaging in goals-of-care discussions with their
      physicians. The challenges of addressing goals of care in patients with
      malignancy, end-stage renal disease, and heart failure have been studied.
      However, there is sparse literature on addressing goals of care throughout the
      dynamic process of transplant assessment and listing. We propose the concept of
      an organ transplant imperative, which is the perceived obligation by patients and
      health care providers to proceed with organ transplant and to avoid advance care
      planning and triggered goals-of-care discussions, even in situations in which
      patients' clinical trajectories have worsened, resulting in poor quality of life
      and low likelihood of meaningful survival. We situate this concept within the
      paradigms of clinical inertia and the treatment and technological imperatives. We
      illustrate this concept by describing a patient with end-stage liver disease
      (ESLD) who was hoping for a liver transplant, who was caught between the
      conflicting perspectives of specialist and primary care physicians, and who died
      of complications of ESLD without experiencing the benefits of advance care
      planning. Greater awareness of the transplant imperative should generate a shared
      understanding among specialists, generalists, and patients and will provide
      opportunities for more formalized involvement of palliative medicine experts in
      the care of transplant patients.

PMID- 28499513
TI  - Cardiorespiratory Fitness and All-Cause Mortality in Men With Emotional Distress.
AB  - OBJECTIVE: Mental health and emotional disorders are often associated with higher
      mortality risk. Whether higher cardiorespiratory fitness (CRF) reduces the risk
      for all-cause mortality in individuals with emotional distress is not well known.
      PATIENTS AND METHODS: Participants were 5240 men (mean age 46.5+/-9.5 years) with
      emotional distress (including depression, anxiety, thoughts of suicide, or a
      history of psychiatric or psychological counseling) who completed an extensive
      medical examination between 1987 and 2002, and were followed for all-cause
      mortality through December 31, 2003. Cardiorespiratory fitness was quantified as
      maximal treadmill exercise test duration and was grouped for analysis as low,
      moderate, and high. Cox proportional hazards regression was used to calculate
      hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 8.7 years (range,
      1.0-16.9 years) and 46,217 person-years of follow-up, there were 128 deaths from
      any cause. Age- and examination year-adjusted all-cause mortality rates per
      10,000 person-years according to low, moderate, and high CRF groups were 64.7
      (95% CI, 44.9-89.3), 28.0 (95% CI, 23.8-31.5), and 19.6 (95% CI, 17.1-21.6)
      (trend P<.001) in men who reported any emotional distress. Overall, the
      multivariable-adjusted HRs and 95% CIs across incremental CRF categories were
      1.00 (referent), 0.54 (0.32-0.90), and 0.47 (0.26-0.85), linear trend P =.03.
      CONCLUSION: Among men with emotional distress, higher CRF is associated with
      lower risk of dying, independent of other clinical mortality predictors. Our
      findings underscore the importance of promoting physical activity to maintain a
      healthful level of CRF in individuals with emotional distress.

PMID- 28499514
TI  - Needle Decompression of Tension Pneumothorax with Colorimetric Capnography.
AB  - BACKGROUND: The success of needle decompression for tension pneumothorax is
      variable, and there are no objective measures assessing effective decompression.
      Colorimetric capnography, which detects carbon dioxide present within the pleural
      space, may serve as a simple test to assess effective needle decompression.
      METHODS: Three swine underwent traumatically induced tension pneumothorax
      (standard of care, n = 15; standard of care with needle capnography, n = 15).
      Needle thoracostomy was performed with an 8-cm angiocatheter. Similarly,
      decompression was performed with the addition of colorimetric capnography.
      Subjective operator assessment of decompression was recorded and compared with
      true decompression, using thoracoscopic visualization for both techniques. Areas
      under receiver operating curves were calculated and pairwise comparison was
      performed to assess statistical significance (P < .05). RESULTS: The detection of
      decompression by needle colorimetric capnography was found to be 100% accurate
      (15 of 15 attempts), when compared with thoracoscopic assessment (true
      decompression). Furthermore, it accurately detected the lack of tension
      pneumothorax, that is, the absence of any pathologic/space-occupying lesion, in
      100% of cases (10 of 10 attempts). Standard of care needle decompression was
      detected by operators in 9 of 15 attempts (60%) and was detected in 3 of 10
      attempts when tension pneumothorax was not present (30%). True decompression,
      under direct visualization with thoracoscopy, occurred 15 of 15 times (100%) with
      capnography, and 12 of 15 times (80%) without capnography. Areas under receiver
      operating curves were 0.65 for standard of care and 1.0 for needle capnography (P
      = .002). CONCLUSIONS: Needle decompression with colorimetric capnography provides
      a rapid, effective, and highly accurate method for eliminating operator bias for
      tension pneumothorax decompression. This may be useful for the treatment of this
      life-threatening condition.

PMID- 28499516
TI  - Improving CPR Performance.
AB  - Cardiac arrest continues to represent a public health burden with most patients
      having dismal outcomes. CPR is a complex set of interventions requiring
      leadership, coordination, and best practices. Despite the widespread adoption of
      new evidence in various guidelines, the provision of CPR remains variable with
      poor adherence to published recommendations. Key steps health-care systems can
      take to enhance the quality of CPR and, potentially, to improve outcomes, include
      optimizing chest compressions, avoiding hyperventilation, encouraging
      intraosseous access, and monitoring capnography. Feedback devices provide
      instantaneous guidance to the rescuer, improve rescuer technique, and could
      impact patient outcomes. New technologies promise to improve the resuscitation
      process: mechanical devices standardize chest compressions, capnography guides
      resuscitation efforts and signals the return of spontaneous circulation, and
      intraosseous devices minimize interruptions to gain vascular access. This review
      aims at identifying a discreet group of interventions that health-care systems
      can use to raise their standard of cardiac resuscitation.

PMID- 28499515
TI  - Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death
      Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta
      Analysis of Trials.
AB  - BACKGROUND: Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1)
      inhibitors show significant clinical activity in non-small cell lung carcinoma
      (NSCLC). However, they are often associated with potentially fatal immune
      mediated pneumonitis. Preliminary reports of trials suggest a difference in the
      rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the
      overall incidence of pneumonitis and differences according to type of inhibitors
      and prior chemotherapy use. METHODS: MEDLINE, Embase, and Scopus databases were
      searched up to November 2016. Rates of pneumonitis of any grade and grade >= 3
      from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab,
      durvalumab, and avelumab as single agents in NSCLC were collected. The incidence
      of pneumonitis across trials was calculated using DerSimonian-Laird random
      effects models. We compared incidences between PD-1 and PD-L1 inhibitors and
      between treatment naive and previously treated patients. RESULTS: Nineteen trials
      (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806])
      were identified. PD-1 inhibitors were found to have statistically significant
      higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%;
      95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1
      inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis
      (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive
      patients had higher incidence of grade 1 through 4 pneumonitis compared with
      previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P
      = .03). CONCLUSIONS: There was a higher incidence of pneumonitis with use of PD-1
      inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more
      common in treatment naive patients.

PMID- 28499517
TI  - Post-Orgasmic Illness Syndrome: Where Are We?

PMID- 28499518
TI  - Combined Artificial Urinary Sphincter and Penile Implant Surgery: Good or Bad
      Idea?

PMID- 28499519
TI  - Association Between Sexual Problems and Relationship Satisfaction Among People
      With Cardiovascular Disease.
AB  - BACKGROUND: Relationship satisfaction is generally positively correlated with
      sexual satisfaction, but this relation has been poorly examined in people with
      cardiovascular disease who are at increased risk of sexual problems compared with
      the general population. AIM: To document reported changes to sex after a
      diagnosis of cardiac disease and determine whether there is an association
      between sexual function and relationship satisfaction. METHODS: Semistructured
      telephone interviews focused on relationship satisfaction and sexual problems
      were conducted with 201 people with cardiovascular disease who were currently in
      a sexual relationship with one main partner and were recruited from six hospital
      cardiac rehabilitation centers in Ireland. Comparisons between groups were
      conducted using t-tests and multivariate analysis of variance for continuous
      variables and chi2 tests for categorical variables. Predictors of relationship
      satisfaction were assessed using multiple linear regression analysis. OUTCOMES:
      Data were gathered on demographic and clinical variables, sexual problems, and
      relationship satisfaction, including satisfaction with the physical, emotional,
      affection, and communication aspects of relationships. RESULTS: Just less than
      one third of participants (n = 61, 30.3%) reported that sex had changed for the
      worse since their cardiac event or diagnosis, with approximately half of these
      stating that this was a serious problem for them. Satisfaction with relationships
      was high among patients surveyed; more than 70% of the sample reported being very
      or extremely satisfied with the physical and emotional aspects and showing
      affection during sex. Satisfaction with communication about sex was lower, with
      only 58% reporting being very or extremely satisfied. We did not find significant
      associations between reporting of sexual problems or deterioration of sex as a
      result of disease and relationship satisfaction. CLINICAL IMPLICATIONS: Cardiac
      rehabilitation programs should address these sexual problems, potentially by
      enhancing communication within couples about sex. STRENGTHS AND LIMITATIONS: The
      strength is that data are presented on the sexual experiences and relationship
      satisfaction of a relatively large sample of people diagnosed with cardiac
      disease, a relatively underexplored research area. Limitations include the
      possibility of selection bias of study participants and bias associated with self
      report measurement. CONCLUSIONS: Sexual problems were significant in this
      population but were not related to relationship satisfaction in this cross
      sectional survey. Byrne M, Murphy P, D'Eath M, et al. Association Between Sexual
      Problems and Relationship Satisfaction Among People With Cardiovascular Disease.
      J Sex Med 2017;14:666-674.

PMID- 28499520
TI  - Prevalence and Predictors of Low Sexual Desire, Sexually Related Personal
      Distress, and Hypoactive Sexual Desire Dysfunction in a Community-Based Sample of
      Midlife Women.
AB  - BACKGROUND: Low desire is the most common sexual problem in women at midlife.
      Prevalence data are limited by lack of validated instruments or exclusion of un
      partnered or sexually inactive women. AIM: To document the prevalence of and
      factors associated with low desire, sexually related personal distress, and
      hypoactive sexual desire dysfunction (HSDD) using validated instruments. METHODS:
      Cross-sectional, nationally representative, community-based sample of 2,020
      Australian women 40 to 65 years old. OUTCOMES: Low desire was defined as a score
      no higher than 5.0 on the desire domain of the Female Sexual Function Index
      (FSFI); sexually related personal distress was defined as a score of at least
      11.0 on the Female Sexual Distress Scale-Revised; and HSDD was defined as a
      combination of these scores. The Menopause Specific Quality of Life Questionnaire
      was used to document menopausal vasomotor symptoms. The Beck Depression Inventory
      II was used to identify moderate to severe depressive symptoms (score >= 20).
      RESULTS: The prevalence of low desire was 69.3% (95% CI = 67.3-71.3), that of
      sexually related personal distress was 40.5% (95% CI = 38.4-42.6), and that of
      HSDD was 32.2% (95% CI = 30.1-34.2). Of women who were not partnered or sexually
      active, 32.4% (95% CI = 24.4-40.2) reported sexually related personal distress.
      Factors associated with HSDD in an adjusted logistic regression model included
      being partnered (odds ratio [OR] = 3.30, 95% CI = 2.46-4.41), consuming alcohol
      (OR = 1.48, 95% CI = 1.16-1.89), vaginal dryness (OR = 2.08, 95% CI = 1.66-2.61),
      pain during or after intercourse (OR = 1.63, 95% CI = 1.27-2.09), moderate to
      severe depressive symptoms (OR = 2.69, 95% CI 1.99-3.64), and use of psychotropic
      medication (OR = 1.42, 95% CI = 1.10-1.83). Vasomotor symptoms were not
      associated with low desire, sexually related personal distress, or HSDD. CLINICAL
      IMPLICATIONS: Given the high prevalence, clinicians should screen midlife women
      for HSDD. STRENGTHS AND LIMITATIONS: Strengths include the large size and
      representative nature of the sample and the use of validated tools. Limitations
      include the requirement to complete a written questionnaire in English. Questions
      within the FSFI limit the applicability of FSFI total scores, but not desire
      domain scores, in recently sexually inactive women, women without a partner, and
      women who do not engage in penetrative intercourse. CONCLUSIONS: Low desire,
      sexually related personal distress, and HSDD are common in women at midlife,
      including women who are un-partnered or sexually inactive. Some factors
      associated with HSDD, such as psychotropic medication use and vaginal dryness,
      are modifiable or can be treated with safe and effective therapies. Worsley R,
      Bell RJ, Gartoulla P, Davis SR. Prevalence and Predictors of Low Sexual Desire,
      Sexually Related Personal Distress, and Hypoactive Sexual Desire Dysfunction in a
      Community-Based Sample of Midlife Women. J Sex Med 2017;14:675-686.

PMID- 28499521
TI  - Investigating Clinically and Scientifically Useful Cut Points on the Compulsive
      Sexual Behavior Inventory.
AB  - INTRODUCTION: One of the major obstacles to conducting epidemiologic research and
      determining the incidence and prevalence of compulsive sexual behavior (CSB) has
      been the lack of relevant empirically derived cut points on the various
      instruments that have been used to measure the concept. AIM: To further develop
      the Compulsive Sexual Behavior Inventory (CSBI) through exploring predictive
      validity and developing an empirically determined and clinically useful cut point
      for defining CSB. METHODS: A sample of 242 men who have sex with men was
      recruited from various sites in a moderate-size Midwestern city. Participants
      were assigned to a CSB group or a control group using an interview for the
      diagnosis that was patterned after the Structured Clinical Interview for the
      Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. The 22
      item CSBI was administered as part of a larger battery of self-report
      inventories. MAIN OUTCOME MEASURES: Receiver operating characteristic analyses
      were used to compute area-under-the-curve measurements to ascertain the
      predictive validity of the total scale, the control subscale, and the violence
      subscale. Cut points were determined through consensus of experts balancing
      sensitivity and specificity as determined by receiver operating characteristic
      curves. RESULTS: Analyses indicated that the 22-item CSBI was a good predictor of
      group membership, as was the 13-item control subscale. The violence subscale
      added little to the predictive accuracy of the instrument; thus, it likely
      measures something other than CSB. Two relevant cut points were found, one that
      minimized false negatives and another, more conservative cut point that minimized
      false positives. CONCLUSION: The CSBI as currently configured measures two
      different constructions and only the control subscale is helpful in diagnosing
      CSB. Therefore, we decided to eliminate the violence subscale and move forward
      with a 13-item scale that we have named the CSBI-13. Two cut points were
      developed from this revised scale, one that is useful as a clinical screening
      tool and the other, more conservative measurement that is useful for etiologic
      and epidemiologic research. Miner MH, Raymond N, Coleman E, Swinburne Romine R.
      Investigating Clinically and Scientifically Useful Cut Points on the Compulsive
      Sexual Behavior Inventory. J Sex Med 2017;14:715-720.

PMID- 28499522
TI  - Editorial Comment on "Distinguishing Failure to Cure From Complication After
      Penile Prosthesis Implantation".

PMID- 28499523
TI  - Response and Rebuttal to Editorial Comment on "Distinguishing Failure to Cure
      From Complication After Penile Prosthesis Implantation".

PMID- 28499524
TI  - One-Stage Gender-Confirmation Surgery as a Viable Surgical Procedure for Female
      to-Male Transsexuals.
AB  - BACKGROUND: Female-to-male gender-confirmation surgery (GCS) includes removal of
      breasts and female genitalia and complete genital and urethral reconstruction.
      With a multidisciplinary approach, these procedures can be performed in one
      stage, avoiding multistage operations. AIM: To present our results of one-stage
      sex-reassignment surgery in female-to-male transsexuals and to emphasize the
      advantages of single-stage over multistage surgery. METHODS: During a period of 9
      years (2007-2016), 473 patients (mean age = 31.5 years) underwent metoidioplasty.
      Of these, 137 (29%) underwent simultaneous hysterectomy, and 79 (16.7%) underwent
      one-stage GCS consisting of chest masculinization, total transvaginal
      hysterectomy with bilateral adnexectomy, vaginectomy, metoidioplasty, urethral
      lengthening, scrotoplasty, and implantation of bilateral testicular prostheses.
      All surgeries were performed simultaneously by teams of experienced gynecologic
      and gender surgeons. OUTCOMES: Primary outcome measurements were surgical time,
      length of hospital stay, and complication and reoperation rates compared with
      other published data and in relation to the number of stages needed to complete
      GCS. RESULTS: Mean follow-up was 44 months (range = 10-92). Mean surgery time was
      270 minutes (range = 215-325). Postoperative hospital stay was 3 to 6 days (mean
      = 4). Complications occurred in 20 patients (25.3%). Six patients (7.6%) had
      complications related to mastectomy, and one patient underwent revision surgery
      because of a breast hematoma. Two patients underwent conversion of transvaginal
      hysterectomy to an abdominal approach, and subcutaneous perineal cyst, as a
      consequence of colpocleisis, occurred in nine patients. There were eight
      complications (10%) from urethroplasty, including four fistulas, three
      strictures, and one diverticulum. Testicular implant rejection occurred in two
      patients and testicular implant displacement occurred in one patient. CLINICAL
      IMPLICATIONS: Female-to-male transsexuals can undergo complete GCS, including
      mastectomy, hysterectomy, oophorectomy, vaginectomy, and metoidioplasty with
      urethral reconstruction as a one-stage procedure without increased surgical risks
      and complication rates. STRENGTHS AND LIMITATIONS: To our knowledge, this is the
      largest cohort on this topic so far, with good surgical outcomes. Limitations
      include lack of selection or exclusion criteria and lack of other studies with a
      simple approach. For this reason, the technique should be studied further and
      compared with other techniques for female-to-male surgery before it can be
      recommended as an alternative procedure. CONCLUSIONS: Through a multidisciplinary
      approach of experienced teams, one-stage GCS presents a safe, viable, and time-
      and cost-saving procedure. Complication rates do not differ from reported rates
      in multistage surgeries. Stojanovic B, Bizic M, Bencic M, et al. One-Stage Gender
      Confirmation Surgery as a Viable Surgical Procedure for Female-to-Male
      Transsexuals. J Sex Med 2017;14:741-746.

PMID- 28499525
TI  - Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal
      Transgender Female Adolescents.
AB  - BACKGROUND: Cyproterone acetate (CA) is an antiandrogenic progestin commonly used
      in adult transwomen to suppress endogenous androgens, often in combination with
      estrogens to induce feminization. AIM: To assess the (side) effects and
      biochemical changes of CA alone and in combination with estrogens in adolescent
      trans-girls. METHODS: This study was a retrospective analysis of clinical and
      biochemical data from 27 trans-girls who presented at Tanner stage G4 and were
      treated with CA monotherapy for at least 6 months (mean = 12 months) and then in
      combination with incremental doses of estrogens (CA + E; mean = 16 months).
      Statistical analysis of data included paired or unpaired Student t-test or
      Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate. OUTCOMES:
      Anthropometrics, reported beneficial and side effects, safety parameters, and
      hormone levels. RESULTS: Physical changes included decrease of facial and non
      facial hair growth. One third showed breast development under CA (Tanner stages
      B2-B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5%
      respectively, during CA + E. Reported side effects during CA and CA + E were
      breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes
      were observed. Main safety parameters showed the following changes. Hemoglobin
      and hematocrit decreased and liver enzymes transiently and modestly increased
      during CA. Triglycerides and cholesterol levels slightly decreased during CA but
      returned to baseline during CA + E; glucose metabolism was unaffected. Relevant
      hormonal changes included a decrease in gonadotropins during CA + E and in total
      and free testosterone levels throughout treatment. Prolactin levels increased
      during CA and were restored during CA + E. CLINICAL IMPLICATIONS: CA produced
      modest feminizing effects in trans-girls and therefore might be a valuable
      alternative in situations in which gonadotropin-releasing hormone analogues are
      not the treatment of choice and/or are not reimbursed. STRENGTHS AND LIMITATIONS:
      This is the first study to report on the effects of CA in the treatment of trans
      girls and one of the few to report on the use of estrogens in this population.
      Limitations are the modest sample size and the retrospective nature of this
      study. CONCLUSION: Treatment with CA in late-pubertal trans-girls overall was
      safe and well tolerated and induced mild clinical and biochemical feminizing
      changes. Rapid further feminization was observed with incremental doses of E.
      Tack LJW, Heyse R, Craen M, et al. Consecutive Cyproterone Acetate and Estradiol
      Treatment in Late-Pubertal Transgender Female Adolescents. J Sex Med 2017;14:747
      757.

PMID- 28499526
TI  - Empirically Supported Incentive Model of Sexual Response Ignored.

PMID- 28499527
TI  - Contraception: Menarche to Menopause.
AB  - Contraception services should be part of routine health care maintenance in
      reproductive-aged women, especially in light of the fact that approximately 50%
      of pregnancies in the United States remain unplanned. Barrier methods, especially
      condoms, may play a role in sexually transmitted disease prevention but are less
      efficacious for pregnancy avoidance. There are several available hormonal
      contraceptive options, including the combination hormonal pill, progestin-only
      pill, combination hormonal patches and rings, injectable progestins, implantable
      progestins, intrauterine devices (copper or progestin), and permanent
      sterilization. These methods have varying efficacy, often related to patient
      compliance or tolerance of side effects.

PMID- 28499528
TI  - Vaginitis: Beyond the Basics.
AB  - Vaginal complaints are one of the most common reasons women seek the advice of a
      health care provider. Uncomplicated infections such as vulvovaginal candidiasis,
      bacterial vaginosis, or trichomoniasis are easy to diagnose and treat. However,
      about 8% of patients will have a more complicated course with failure to respond
      to treatment or rapid recurrence of symptoms. Understanding the need for a
      methodical, diagnostic approach to help these women with recurrent or refractory
      cases of vaginal symptoms will aid the clinician achieve successful patient
      outcomes.

PMID- 28499529
TI  - Abnormal Uterine Bleeding: Current Classification and Clinical Management.
AB  - Abnormal uterine bleeding is now classified and categorized according to the
      International Federation of Gynecology and Obstetrics classification system: PALM
      COEIN. This applies to nongravid women during their reproductive years and allows
      more clear designation of causes, thus aiding clinical care and future research.

PMID- 28499530
TI  - Recognition and Therapeutic Options for Malignancy of the Cervix and Uterus.
AB  - An update on the current epidemiology and a review of the risk factors of
      cervical and endometrial cancers are discussed. Cervical cancer prevention with a
      focus on human papillomavirus vaccination and cervical cancer screening is
      reviewed, emphasizing the new focus of less frequent intervention in an effort to
      maintain high rates of early detection of disease while decreasing unnecessary
      and anxiety-provoking colposcopies, biopsies, and excisional procedures. The
      replacement of traditional endometrial hyperplasia terminology with more relevant
      clinical categories, with an emphasis on the introduction of endometrial
      intraepithelial neoplasia, is presented. Fertility-sparing options in the
      management of early cervical and endometrial cancers are reviewed.

PMID- 28499531
TI  - Gestational Diabetes: Diagnosis, Classification, and Clinical Care.
AB  - Gestational diabetes mellitus (GDM) affects approximately 6% of pregnant women,
      and prevalence is increasing in parallel with the obesity epidemic. Protocols for
      screening/diagnosing GDM are controversial with several guidelines available.
      Treatment of GDM results in a reduction in the incidence of preeclampsia,
      shoulder dystocia, and macrosomia. If diet and lifestyle changes do not result in
      target glucose levels, then treatment with metformin, glyburide, or insulin
      should begin. It is generally recommended that pregnancies complicated by GDM do
      not go beyond term. For women identified to have prediabetes, intensive lifestyle
      intervention and metformin have been shown to prevent or delay progression to
      type 2 diabetes.

PMID- 28499532
TI  - Updates on the Recognition, Prevention and Management of Hypertension in
      Pregnancy.
AB  - Systematic reviews with meta-analysis represent the highest level of evidence
      used to guide clinical practice. The defining criteria used to diagnose
      preeclampsia have evolved, and will likely continue to evolve. Proteinuria is
      sufficient but not necessary when defining preeclampsia. Hypertension without
      proteinuria but with severe features is diagnostic. The methods used to measure
      urinary protein have changed. The gold standard remains the 24-hour urine test.
      The efficacy of low-dose aspirin in preventing preeclampsia is a function of
      baseline risk. Data suggest that treating mild to moderate blood pressure has
      clear maternal benefits with little fetal or neonatal risk.

PMID- 28499533
TI  - Obstetric Emergencies: Shoulder Dystocia and Postpartum Hemorrhage.
AB  - Shoulder dystocia and postpartum hemorrhage represent two of the most common
      emergencies faced in obstetric clinical practice, both requiring prompt
      recognition and management to avoid significant morbidity or mortality. Shoulder
      dystocia is an uncommon, unpredictable, and unpreventable obstetric emergency and
      can be managed with appropriate intervention. Postpartum hemorrhage occurs more
      commonly and carries significant risk of maternal morbidity. Institutional
      protocols and algorithms for the prevention and management of shoulder dystocia
      and postpartum hemorrhage have become mainstays for clinicians. The goal of this
      review is to summarize the diagnosis, incidence, risk factors, and management of
      shoulder dystocia and postpartum hemorrhage.

PMID- 28499534
TI  - Prenatal Diagnosis: Screening and Diagnostic Tools.
AB  - The American Congress of Obstetricians and Gynecologists recommends that all
      pregnant women be offered aneuploidy screening or diagnostic testing. A myriad of
      screening and testing options are available to patients based on their risk
      profile and gestational age. Screening options include traditional serum analyte
      screening, such as first-trimester screening or quadruple screening, and more
      recently, cell-free DNA. Diagnostic testing choices include chorionic villus
      sampling and amniocentesis. The number of screening and diagnostic modalities
      complicates prenatal counseling for physicians and can be difficult for patients
      to grasp. Appropriate pretest and posttest counseling is important to ensure
      adequate understanding of results and ensure testing strategy is concordant with
      patient goals.

PMID- 28499535
TI  - Cancer Recognition and Screening for Common Breast Disorders and Malignancy.
AB  - Breast cancer is predicted to be the most common newly diagnosed cancer in women
      in 2016. Screening mammography is the most commonly used method for the detection
      of breast cancer in women of average risk. A genetic risk assessment is
      recommended for women with a greater than 20% to 25% chance of having a
      predisposition to breast and ovarian cancer. Evaluation of a breast mass begins
      with a detailed history, assessment for cancer risk, and physical examination.

PMID- 28499536
TI  - Recognizing and Managing Common Urogynecologic Disorders.
AB  - Many women experience urogynecologic or pelvic floor disorders, especially
      urinary incontinence and pelvic organ prolapse. The obstetrician/gynecologist is
      often the first health care professional to evaluate and treat these disorders.
      Treatments include pelvic floor muscle training, behavioral therapies, oral
      medications, neuromodulation, intradetrusor medications, and surgery. When
      approaching the woman with symptomatic prolapse, familiarity with pessaries and
      various surgical procedures aid in counseling. Referral to a pelvic floor
      physical therapist or to a female pelvic medicine and reconstructive surgeon
      should be considered. Increasing attention to data on cost-effectiveness is a
      necessity.

PMID- 28499537
TI  - The Menopausal Transition.
AB  - A clear understanding of the physiology of the menopausal transition, clinical
      symptoms, and physical changes is essential for individualized patient
      management, maximizing benefits and minimizing risks for the present and the
      future. Menopause, defined by amenorrhea for 12 consecutive months, is determined
      retrospectively and represents a permanent end to menses. Many physical changes
      occur during the menopausal transition and beyond. Knowledge of symptoms and
      findings experienced by women undergoing the menopausal transition allow
      individualized care- improving quality of life and enhancing wellbeing for years
      to come.

PMID- 28499538
TI  - Burnout in Obstetricians and Gynecologists.
AB  - It is estimated that 40% to 75% of obstetricians and gynecologists currently
      suffer from professional burnout, making the lifetime risk a virtual certainty.
      Although these statistics make for a dismal view of the profession, if the causes
      and symptoms can be identified simple steps can be implemented to reverse the
      threat. With a little care, the enjoyment of practice can be restored and the
      sense of reward and the value of service can be returned.

PMID- 28499539
TI  - Lifelong Learning Requires Maintenance of Knowledge.

PMID- 28499540
TI  - Maintenance of Knowledge.

PMID- 28499541
TI  - Sequence analysis of haemagglutinin and neuraminidase of H1N1 strain from a
      patient coinfected with Mycobacterium tuberculosis.
AB  - The 2009 H1N1 pandemic (H1N1pdm09) was associated with a considerable influenza
      related morbidity and mortality. Among the complications, Mycobacterial
      tuberculosis was recorded as a coinfection with influenza in rare cases. The full
      length sequences of the viral haemagglutinin and neuraminidase of H1N1pdm09
      influenza A virus were analyzed from a recently infected patient. The patient was
      chronically infected with Mycobacterium tuberculosis. Molecular modelling and in
      silico docking of the virus, and other selected strains with the drug oseltamivir
      were conducted and compared. Sequence analysis of the viral haemagglutinin
      revealed it to be closely related to the 6B.1 clade, with high identity to the
      circulating H1N1pdm09 strains, and confirmed that the virus still harbouring high
      affinity to the alpha-2,6-sialic acid human receptor. The viral neuraminidase
      showed high identity to the neuraminidase of the recently circulating strains of
      the virus with no evidence of the development of oseltamivir-resistant mutants.
      Regular monitoring of the circulating strains is recommended to screen for a
      possible emergence of drug-resistant strains.

PMID- 28499542
TI  - Development of a taqman-based real-time PCR assay for the rapid and specific
      detection of novel duck- origin goose parvovirus.
AB  - A real-time PCR assay was developed for specific detection of novel duck-origin
      goose parvovirus (N-GPV), the etiological agent of duck beak atrophy and dwarfism
      syndrome (BADS). The detection limit of the assay was 102 copies. The assay was
      useful in the prevention and control of BADS.

PMID- 28499543
TI  - [Congenital anterior urethral diverticulum in children: A case report].

PMID- 28499544
TI  - Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors
      in children and adolescents: beware of cyclin D1 expression in clear cell sarcoma
      of the kidney and CIC-DUX4 fusion-positive sarcomas. Comment on Magro et al
      (2016).

PMID- 28499546
TI  - Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors
      in children and adolescents: beware of cyclin D1 expression in clear cell sarcoma
      of the kidney and CIC-DUX4 fusion-positive sarcomas. Comment on Magro et al
      (2016)-reply.

PMID- 28499545
TI  - Mucoepidermoid carcinoma post-radioactive iodine treatment of papillary thyroid
      carcinoma: unique presentation and putative etiologic association.
AB  - We report the development of mucoepidermoid carcinomas of the parotid gland in 2
      adult patients after a relatively short duration of radioactive iodine (RAI)
      treatment of papillary thyroid carcinoma. Both instances, together with those
      previously reported, underscore the selective nature of the mucoepidermoid
      carcinoma phenotype development in patients with papillary thyroid carcinoma as a
      consequence of RAI treatment. Efforts to alleviate salivary pathophysiologic
      damage by RAI in these patients are warranted.

PMID- 28499547
TI  - The dark side of T1 non-appendiceal small bowel neuroendocrine tumors.

PMID- 28499549
TI  - Open letter to WHO DG candidates: reply from Sania Nishtar.

PMID- 28499548
TI  - Mortality risks associated with emergency admissions during weekends and public
      holidays: an analysis of electronic health records.
AB  - BACKGROUND: Weekend hospital admission is associated with increased mortality,
      but the contributions of varying illness severity and admission time to this
      weekend effect remain unexplored. METHODS: We analysed unselected emergency
      admissions to four Oxford University National Health Service hospitals in the UK
      from Jan 1, 2006, to Dec 31, 2014. The primary outcome was death within 30 days
      of admission (in or out of hospital), analysed using Cox models measuring time
      from admission. The primary exposure was day of the week of admission. We
      adjusted for multiple confounders including demographics, comorbidities, and
      admission characteristics, incorporating non-linearity and interactions. Models
      then considered the effect of adjusting for 15 common haematology and
      biochemistry test results or proxies for hospital workload. FINDINGS: 257 596
      individuals underwent 503 938 emergency admissions. 18 313 (4.7%) patients
      admitted as weekday energency admissions and 6070 (5.1%) patients admitted as
      weekend emergency admissions died within 30 days (p<0.0001). 9347 individuals
      underwent 9707 emergency admissions on public holidays. 559 (5.8%) died within 30
      days (p<0.0001 vs weekday). 15 routine haematology and biochemistry test results
      were highly prognostic for mortality. In 271 465 (53.9%) admissions with complete
      data, adjustment for test results explained 33% (95% CI 21 to 70) of the excess
      mortality associated with emergency admission on Saturdays compared with
      Wednesdays, 52% (lower 95% CI 34) on Sundays, and 87% (lower 95% CI 45) on public
      holidays after adjustment for standard patient characteristics. Excess mortality
      was predominantly restricted to admissions between 1100 h and 1500 h
      (pinteraction=0.04). No hospital workload measure was independently associated
      with mortality (all p values >0.06). INTERPRETATION: Adjustment for routine test
      results substantially reduced excess mortality associated with emergency
      admission at weekends and public holidays. Adjustment for patient-level factors
      not available in our study might further reduce the residual excess mortality,
      particularly as this clustered around midday at weekends. Hospital workload was
      not associated with mortality. Together, these findings suggest that the weekend
      effect arises from patient-level differences at admission rather than reduced
      hospital staffing or services. FUNDING: NIHR Oxford Biomedical Research Centre.

PMID- 28499550
TI  - Data linkage studies can help to explain the weekend effect.

PMID- 28499551
TI  - Lessons learned from a single institution's retrospective analysis of emergent
      cesarean delivery following external cephalic version with and without neuraxial
      anesthesia.
AB  - OBJECTIVES: To evaluate the risk of emergent cesarean delivery with the use of
      neuraxial anesthesia for external cephalic version in a single practice.
      BACKGROUND: Randomized trials have shown increased external cephalic version
      success when neuraxial anesthesia is used, without additional risk. We
      hypothesized that in our actual clinical practice, outside the confines of
      randomized trials, neuraxial anesthesia could be associated with an increased
      risk of emergent cesarean delivery. METHODS: This retrospective cohort study
      included all women who underwent external cephalic version at a single
      institution with and without neuraxial anesthesia. The primary outcome was the
      incidence of emergent cesarean delivery (defined as delivery within 4hours of
      version). Secondary outcomes were version success and ultimate mode of delivery.
      RESULTS: A total of 135 women underwent external cephalic version procedures; 58
      with neuraxial anesthesia (43.0%) and 77 without (57.0%). Location of the
      procedure, tocolytic therapy, and gestational age were different between groups.
      An increased rate of emergent cesarean delivery was found in procedures with
      neuraxial anesthesia compared to procedures without (5/58 (8.6%) compared to 0/77
      (0.0%); 95% CI for difference, 1.4 to 15.8%; P=0.013). CONCLUSION: In this single
      hospital's practice, patients who may be at higher risk of complications and have
      a lesser likelihood of success were provided NA for ECV. As a result, the use of
      neuraxial anesthesia for external cephalic version was associated with a higher
      rate of emergent cesarean delivery. Obstetric and anesthetic practices should
      evaluate their patient selection and procedure protocol for external cephalic
      version under neuraxial anesthesia.

PMID- 28499552
TI  - Puerperal ventral epidural hematoma after epidural labor analgesia.
AB  - Serious complications in obstetric anesthesia are a rare occurrence. High
      neuraxial block, respiratory arrest in labor and delivery, and an unrecognized
      spinal catheter are among the most frequently reported serious complications. A
      serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial
      hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We
      present a case of a puerperal spinal epidural hematoma following epidural labor
      analgesia. The patient presented with foot drop, which resolved after
      conservative treatment. We reviewed the epidemiology, clinical manifestations and
      treatment options for this rare complication.

PMID- 28499553
TI  - Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as
      well as mucosal immunity in mice.
AB  - Sporadic, yet frequent human infections with avian H5N1 influenza A viruses
      continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted
      H5N1 vaccines warrants developing novel adjuvants and formulations as well as
      alternate delivery systems to improve their immunogenicity and efficacy. Here, we
      show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer
      membrane proteins non-covalently linked to Shigella flexneri 2a
      lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion
      H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model.
      Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination
      inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated
      immunity that resulted in complete protection against a lethal challenge with a
      homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005
      (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin
      increased the frequency of lymphoid- as well as local tissue-resident antibody
      secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4
      T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with
      Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce
      both cellular and humoral immune responses, enhance protection against challenge
      with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose
      sparing.

PMID- 28499554
TI  - Effectiveness of HPV vaccines against genital warts in women from Valencia,
      Spain.
AB  - OBJECTIVES: To assess the effectiveness of the HPV vaccines in preventing genital
      warts in young women. DESIGN: Population-based study using health databases.
      SETTING: Valencian Community (Spain). PARTICIPANTS: All girls and women aged 14
      19years who were registered in the Valencian Community between January 2009 and
      December 2014 (n=279,787). MAIN OUTCOME MEASURES: Incident cases of genital warts
      were defined as the first activation of diagnosis code ICD-9-CM 078.11 (Condyloma
      acuminatum) in primary care and outpatient clinics during the study period.
      RESULTS: There were 612 cases of genital warts. The overall incidence rate was
      75.8/100,000 person-years (95% CrI 69.7-81.8). There was a decrease in genital
      warts when female candidates to be vaccinated with quadrivalent HPV vaccine
      reached the age of 18 (in 2012), compared to previous years. Incidence of genital
      warts in unvaccinated women and those who received the bivalent vaccine was
      higher than in girls and women who received the quadrivalent HPV vaccine. The
      effectiveness of a three-dose regimen of the quadrivalent HPV vaccine was 77% (95
      CrI: 66-85%), whereas that of a single dose was 61% (95 CrI: 20-87%). No
      effectiveness was seen with a full vaccination course with the bivalent HPV
      vaccine. CONCLUSIONS: Three doses of the quadrivalent HPV vaccine were effective
      against genital warts in our population. Moreover, with low vaccine coverage the
      incidence of genital warts decreased only in the vaccinated.

PMID- 28499555
TI  - Evaluating biomechanics of user-selected sitting and standing computer
      workstation.
AB  - A standing computer workstation has now become a popular modern work place
      intervention to reduce sedentary behavior at work. However, user's interaction
      related to a standing computer workstation and its differences with a sitting
      workstation need to be understood to assist in developing recommendations for use
      and set up. The study compared the differences in upper extremity posture and
      muscle activity between user-selected sitting and standing workstation setups.
      Twenty participants (10 females, 10 males) volunteered for the study. 3-D
      posture, surface electromyography, and user-reported discomfort were measured
      while completing simulated tasks with each participant's self-selected
      workstation setups. Sitting computer workstation associated with more non-neutral
      shoulder postures and greater shoulder muscle activity, while standing computer
      workstation induced greater wrist adduction angle and greater extensor carpi
      radialis muscle activity. Sitting computer workstation also associated with
      greater shoulder abduction postural variation (90th-10th percentile) while
      standing computer workstation associated with greater variation for should
      rotation and wrist extension. Users reported similar overall discomfort levels
      within the first 10 min of work but had more than twice as much discomfort while
      standing than sitting after 45 min; with most discomfort reported in the low back
      for standing and shoulder for sitting. These different measures provide
      understanding in users' different interactions with sitting and standing and by
      alternating between the two configurations in short bouts may be a way of
      changing the loading pattern on the upper extremity.

PMID- 28499556
TI  - Reply to: "Pressure volume curves in cirrhosis: More than meets the eye".

PMID- 28499557
TI  - The effect of focal cortical frontal and posterior lesions on recollection and
      familiarity in recognition memory.
AB  - Recognition memory can be subdivided into two processes: recollection (a
      contextually rich memory) and familiarity (a sense that an item is old). The
      brain network supporting recognition encompasses frontal, parietal and medial
      temporal regions. Which specific regions within the frontal lobe are critical for
      recollection vs. familiarity, however, are unknown; past studies of focal lesion
      patients have yielded conflicting results. We examined patients with focal
      lesions confined to medial polar (MP), right dorsal frontal (RDF), right
      frontotemporal (RFT), left dorsal frontal (LDF), temporal, and parietal regions
      and matched controls. A series of words and their humorous definitions were
      presented either auditorily or visually to all participants. Recall, recognition,
      and source memory were tested at 30 min and 24 h delay, along with
      "remember/know" judgments for recognized items. The MP, RDF, temporal and
      parietal groups were impaired on subjectively reported recollection; their intact
      recognition performance was supported by familiarity. None of the groups were
      impaired on cued recall, recognition familiarity or source memory. These findings
      suggest that the MP and RDF regions, along with parietal and temporal regions,
      are necessary for subjectively-reported recollection, while the LDF and right
      frontal ventral regions, as those affected in the RTF group, are not.

PMID- 28499558
TI  - Influence of response bias and internal/external source on lateral posterior
      parietal successful retrieval activity.
AB  - In studies of recognition memory, regions of the lateral posterior parietal
      cortex exhibit greater activity (as indexed by the fMRI BOLD signal) during
      correct recognition of "old" (studied) items than correct rejection of "new"
      (unstudied) items. This effect appears to be source-sensitive, with greater
      activity associated with recognition of perceived than imagined events. Parietal
      successful retrieval activity also varies with response bias, or the tendency to
      be conservative about making "old" judgments. Here, we examined whether
      differences in response bias associated with recognition judgments of perceived
      and imagined events could account for source-based differences in LPPC activity.
      Participants perceived and imagined items in response to cue words and then at
      test, made recognition judgments in blocks that knowingly contained either a high
      or low proportion of old to new trials. While participants were indeed more
      conservative when making judgments about perceived than imagined events, the
      neuroimaging results demonstrated that response bias and source effects occurred
      in non-overlapping parietal regions. These findings suggest that source-based
      differences in LPPC activity cannot be explained by differences in response bias
      associated with recognizing perceived and imagined events.

PMID- 28499559
TI  - Identifying Psychosocial Distress and Stressors Using Distress-screening
      Instruments in Patients With Localized and Advanced Penile Cancer.
AB  - BACKGROUND: We examined the effects of treatment on the psychological well-being
      of patients with localized or advanced penile cancer using screening
      questionnaires to determine the consecutive need for psychosocial care. Penile
      cancer is a rare, but highly aggressive, malignancy. The psychological stress of
      patients with penile cancer arises from the cancer diagnosis per se and the
      corresponding consequences of treatment. In addition, cancer-specific distress
      results (eg, fear of metastasis, progression, relapse, death). Studies of the
      psychosocial stress of penile cancer patients are rare. MATERIAL AND METHODS: We
      undertook a prospective analysis of the data from patients with penile cancer who
      had undergone surgery or chemotherapy from August 2014 to October 2016 at our
      department. Patients were evaluated using standardized questionnaires for stress
      screening and the identification for the need for psychosocial care (National
      Comprehensive Cancer Network Distress Thermometer and Hornheider screening
      instrument) and by assessing the actual use of psychosocial support. RESULTS: The
      average stress level was 4.5. Of all the patients, 42.5% showed increased care
      needs at the time of the survey. Younger patients, patients undergoing
      chemotherapy, and patients with recurrence were significantly more integrated
      with the psychosocial care systems. Finally, 67% of all patients received
      inpatient psychosocial care. CONCLUSION: Owing to the potentially mutilating
      surgery, patients with penile cancer experience increased psychological stress
      and, consequently, have an increased need for psychosocial care. Therefore, the
      emotional stress of these patients should be recognized and support based on
      interdisciplinary collaboration offered.

PMID- 28499560
TI  - The Challenge of Mental Health Care for Veterans and Their Families.

PMID- 28499561
TI  - Grandmothers and Self-Management of Depressive Symptoms.

PMID- 28499562
TI  - Educating Undergraduate Psychiatric Mental Health Nursing Students in Screening,
      Brief Intervention, Referral to Treatment (SBIRT) Using an Online, Interactive
      Simulation.

PMID- 28499563
TI  - Roles of Psychiatry Nurses Within a Therapeutic Environment of Psychiatry Clinics
      in Turkey.
AB  - OBJECT: The object of this study is to determine the roles of psychiatry nurses
      within the therapeutic environment of psychiatry clinics in Turkey. METHODS: This
      study was performed in a cross-sectional and descriptive design in 195 institutes
      comprising psychiatry clinics in Turkey. RESULTS: When the responsibilities of
      nurses for clinical activities were asked, the following answers were obtained:
      playing with patients or painting at a rate of 54,4%. It was determined that in
      the majority of psychiatry clinics, there were educational activities which were
      conducted by nurses. CONCLUSION: The researchers propose that the increase in the
      roles and responsibilities of nurses in such activities be supported.

PMID- 28499564
TI  - Socio-demographic and Psychological Correlates of Posttraumatic Growth among
      Korean Americans with a History of Traumatic Life Experiences.
AB  - This study examined socio-demographic and psychological correlates of
      posttraumatic growth (PTG) among Korean Americans (KAs) with traumatic life
      experiences. A total of 286 KAs were included. Being a woman or having a lower
      annual household income had positive associations with PTG, while having no
      religion had a negative association with it. In addition, praying and visiting a
      mental health professional for coping with stress or for psychological problems
      was positively associated with PTG. Higher resilience scores increased PTG, while
      depressive symptoms decreased it. We suggest reinforcing help seeking behaviors
      and accessibility to care facilities, and gender specific strengthening programs
      for enhancing PTG among KAs.

PMID- 28499565
TI  - Relationship Between Caregiving Burden and Anger Level in Primary Caregivers of
      Individuals With Chronic Mental Illness.
AB  - OBJECTIVES: The objective of this study was answer to the question: to what
      extent are the anger of the caregivers of patients diagnosed with schizophrenia
      and their perceived level of burden are related? METHOD: The study is a
      descriptive and correlational study. The information form prepared by the
      researchers which questions the socio-demographic information of the individuals
      along with the "Caregiving Burden Inventory" which examines the burden of the
      caregiver as well as "Trait Anger and Anger Expression Style Scale (TAAES)" which
      determines the anger levels of the caregivers were used. RESULTS: The caregiving
      burdens of the caregivers according to the score averages were determined as
      11.88+/-9.78 for time and dependency burden, 11.93+/-8.46 for developmental
      burden, 8.47+/-6.63 for physical burden, 5.61+/-5.26 for social burden, 6.29+/
      5.25 for emotional burden and the total burden score was determined as 44.19+/
      26.75. According to the trait anger and anger expression style scale score
      averages; trait anger was determined as 15.12+/-5.95, anger expression as 9.70+/
      3.43, anger-in as 15.22+/-4.02, anger control as 28.05+/-5.57 and anger total
      score average as 68.11+/-9.97. CONCLUSION: According to the results obtained from
      this study, caregivers of schizophrenia patients experience developmental,
      physical, social and emotional burdens in addition to trait anger. The caregivers
      of schizophrenia patients need knowledge and support in order to control the
      burden and the anger they experience during the caregiving process.

PMID- 28499566
TI  - Effects of Spiritual Group Therapy on Caregiver Strain in Home Caregivers of the
      Elderly with Alzheimer's Disease.
AB  - INTRODUCTION: Care of patients with Alzheimer's disease is one of the most
      difficult types of care that exposes the caregiver to a high level of care
      strain. The present research aimed at determining the effect of spiritual care on
      caregiver strain of the elderly with Alzheimer's disease. METHODS: An
      experimental study was carried out on 100 caregivers who were selected by
      convenience sampling and randomly divided into intervention, control one and
      control two groups. Group spiritual therapy was performed on the intervention
      group for five weeks, Control one participate in the group sessions without any
      particular interventions, and control two received no interventions. Data was
      collected through a demographic questionnaire and Robinson's (1983) Caregiver
      Strain Index, and analyzed using the Chi-square, Fisher's Exact test, one-way
      analysis of variance and paired t-test. Statistical significance level was
      considered as 0.05. RESULTS: In the intervention group mean of the posttest care
      strain score 32.43+/-2.73 was significantly lower than pretest 37.16+/-1.26
      (P<0.001). The mean posttest score of care strain was significantly lower in the
      intervention group compared to the two other groups (P<0.001). CONCLUSION:
      Spiritual care can reduce care strain in home caregivers of the elderly with
      Alzheimer's disease.

PMID- 28499567
TI  - The Effect of the Psychiatric Nursing Approach Based on the Tidal Model on Coping
      and Self-esteem in People with Alcohol Dependency: A Randomized Trial.
AB  - INTRODUCTION: People with alcohol dependency have lower self-esteem than controls
      and when their alcohol use increases, their self-esteem decreases. Coping skills
      in alcohol related issues are predicted to reduce vulnerability to relapse. It is
      important to adapt care to individual needs so as to prevent a return to the
      cycle of alcohol use. The Tidal Model focuses on providing support and services
      to people who need to live a constructive life. AIM: The aim of the randomized
      study was to determine the effect of the psychiatric nursing approach based on
      the Tidal Model on coping and self-esteem in people with alcohol dependency.
      METHOD: The study was semi-experimental in design with a control group, and was
      conducted on 36 individuals (18 experimental, 18 control). An experimental and a
      control group were formed by assigning persons to each group using the stratified
      randomization technique in the order in which they were admitted to hospital. The
      Coping Inventory (COPE) and the Coopersmith Self-Esteem Inventory (CSEI) were
      used as measurement instruments. The measurement instruments were applied before
      the application and three months after the application. In addition to routine
      treatment and follow-up, the psychiatric nursing approach based on the Tidal
      Model was applied to the experimental group in the One-to-One Sessions. RESULTS:
      The psychiatric nursing approach based on the Tidal Model is an approach which is
      effective in increasing the scores of people with alcohol dependency in positive
      reinterpretation and growth, active coping, restraint, emotional social support
      and planning and reducing their scores in behavioral disengagement. It was seen
      that self-esteem rose, but the difference from the control group did not reach
      significance. DISCUSSION: The psychiatric nursing approach based on the Tidal
      Model has an effect on people with alcohol dependency in maintaining their
      abstinence. IMPLICATIONS FOR PRACTICE: The results of the study may provide
      practices on a theoretical basis for improving coping behaviors and self-esteem
      and facilitating the recovery process of alcohol dependents with implications for
      mental health nursing.

PMID- 28499568
TI  - Risk Factors for Suicide Ideation Among Adolescents: Five-Year National Data
      Analysis.
AB  - This study identified risk factors for suicide ideation among adolescents through
      a secondary analysis using data collected over five years from the 5th-9th Korea
      Youth Risk Behavior Survey. We analyzed 370,568 students' responses to questions
      about suicidality. The risk factors for suicide ideation included demographic
      characteristics, such as gender (girls), low grades, low economic status, and not
      living with one or both parents. Behavioral and mental health risk factors
      affecting suicide ideation were depression, low sleep satisfaction, high stress,
      alcohol consumption, smoking, and sexual activity. Health care providers should
      particularly target adolescents manifesting the above risk factors when
      developing suicide prevention programs for them.

PMID- 28499569
TI  - Prevalence of Major Depression and Its Associations With Demographic and Clinical
      Characteristics and Quality of Life in Chinese Patients With HBV-related Liver
      Diseases.
AB  - BACKGROUND: There are no data about the frequency of major depression in patients
      with liver disease related to Hepatitis B virus (HBV) in China. This study
      examined the prevalence of major depression and its clinical correlates and
      association with quality of life (QOL) in patients with HBV-related liver
      diseases. METHOD: Altogether 634 patients with HBV-related liver diseases met
      study entry criteria and completed the survey. The diagnosis of major depression
      was established with the Mini International Neuropsychiatric Interview (MINI).
      Socio-demographic and clinical characteristics, Global Assessment of Functioning
      (GAF) and QOL were measured. RESULTS: The prevalence of major depression was
      6.4%. Multivariable logistic regression analyses revealed that insomnia (P=0.01,
      OR=5.5, 95%CI=1.4-21.6) and global functioning (P<0.001, OR=0.6, 95% CI=0.5-0.7)
      were independently associated with major depression. Major depression was
      associated with both poor physical (F (1, 634)=4.0, P=0.04) and mental QOL (F (1,
      634)=26.2, P<0.001). CONCLUSIONS: Given the negative impact of depression on
      patients' QOL, more attempts should be made to identify and treat it in HBV
      related diseases.

PMID- 28499570
TI  - The Obsessive Compulsive Inventory-Child Version (OCI-CV): Further Evidence on
      Confirmatory Factor Analytic Structure, Incremental and Criterion Validity in
      Italian Community Children and Adolescents.
AB  - Obsessive Compulsive Inventory-Child Version (OCI-CV) assesses six dimensions of
      OCD symptoms in childhood and adolescence. The current study used confirmatory
      methods to assess factor structure and reliability of the Italian OCI-CV in
      community children and adolescents. 1408 community children and adolescents
      completed the OCI-CV and a subgroup (n=855) completed measures of other anxiety
      and depression symptoms. A six correlated factor structure showed good fit.
      Reliability was excellent for total OCI-CV and for the other scales ranged from
      good to acceptable. The OCI-CV confirmed good properties in terms of factor
      structure and reliability.

PMID- 28499571
TI  - Designing an Internet Intervention for Emerging Adults Who Experience Troubled
      Relationships.
AB  - This article describes how the Internet Intervention Model (IIM) was used as an
      organizing framework to design a theoretically based Internet intervention for
      emerging adults who experience troubled intimate partner relationships. In the
      design process, the team addressed six fundamental questions related to the
      several components of the IIM. Decisions made regarding the design of the
      intervention based on the six questions are described. We focus in particular on
      how the intervention is based on the Theory of Emerging Adulthood and the Theory
      of Narrative Identity.

PMID- 28499572
TI  - A National Survey on Nursing in Canadian ECT Departments.

PMID- 28499573
TI  - Positive Thinking Training Intervention for Caregivers of Persons with Autism:
      Establishing Fidelity.
AB  - More than 3.5 million in the US are diagnosed with autism spectrum disorder (ASD)
      and caregivers experience stress that adversely affects their well-being.
      Positive thinking training (PTT) intervention can minimize that stress. However,
      before testing the effectiveness of PTT, its fidelity must be established. This
      pilot intervention trial examined fidelity of an online PTT intervention for ASD
      caregivers with a random assignment of 73 caregivers to either the online PTT
      intervention or to the control group. Quantitative data [Positive Thinking Skills
      Scale (PTSS)] and qualitative data (online weekly homework) were collected. The
      mean scores for the PTSS improved for the intervention group and decreased for
      the control group post intervention. Evidence for use of PTT was found in
      caregivers' online weekly homework. The findings provide evidence of the
      implementation fidelity of PTT intervention and support moving forward to test
      PTT effectiveness in promoting caregivers' well-being.

PMID- 28499574
TI  - Use of Computer and Mobile Technologies in the Treatment of Depression.
AB  - Major depression (MDD) is a common and disabling disorder. Research has shown
      that most people with MDD receive either no treatment or inadequate treatment.
      Computer and mobile technologies may offer solutions for the delivery of
      therapies to untreated or inadequately treated individuals with MDD. The authors
      review currently available technologies and research aimed at relieving symptoms
      of MDD. These technologies include computer-assisted cognitive-behavior therapy
      (CCBT), web-based self-help, Internet self-help support groups, mobile
      psychotherapeutic interventions (i.e., mobile applications or apps), technology
      enhanced exercise, and biosensing technology.

PMID- 28499575
TI  - Childhood Enuresis: Current Diagnostic Formulations, Salient Findings, and
      Effective Treatment Modalities.
AB  - Enuresis constitutes a frequently encountered problem area for children that may
      adversely affect social and emotional adjustment. This type of incontinence has
      been of concern to the human family for centuries. A brief history of enuresis is
      presented followed by current conceptualizations, diagnostic criteria, prevalence
      rates and psychiatric comorbidities. Historic notions of causation together with
      ineffective, sometimes barbaric treatments are then discussed, ending with a
      presentation of evidence-based treatment modalities, with the urine alarm being
      an essential element of effective treatment. An intervention termed dry bed
      training combines the urine alarm with a series of procedures designed in part to
      reduce relapse potential and should be a primary consideration for implementation
      by treatment professionals. Finally, a brief case study is presented illustrating
      special etiological and treatment considerations with juvenile psychiatric
      patients.

PMID- 28499576
TI  - An Introduction to the Model of Crisis Intervention Procedure for Borderline
      Patients (CIP-BP): A Case Study.
AB  - Borderline personality disorder is highly associated with suicidal behaviors. The
      authors of the current case study present the introduction model of original
      Crisis Intervention Procedure for Borderline Patients (CIP-BP) which is a method
      focused on restoring emotional balance, reducing the severity of symptoms and the
      risk of suicidal behavior, as well as developing optimum solutions for further
      action. Its aim is to enable the patient to regain control of their emotional
      memory, increase autonomy and restore important interpersonal relations by using
      the original resources of this person. The procedure aims at providing nursing
      personnel with a practical tool to effectively avert the crisis and prevent
      further decompensation of BPD patients. Further pre-post study is required to
      determine the effectiveness of the procedure.

PMID- 28499577
TI  - Metabolic regulation of suppressive myeloid cells in cancer.
AB  - Cancer cells rewire their metabolism to promote growth, survival, proliferation
      and long-term maintenance. The common feature of this altered metabolism is the
      increased glucose uptake and fermentation of glucose to lactate, which is
      observed even in the presence of completely functioning mitochondria. This effect
      is known as the 'Warburg Effect' and its intensive investigation in the last
      decade has partially established either its causes or its functions. It is now
      emerging that a major side effect of the Warburg Effect is immunosuppression,
      which limits the immunogenicity of cancer cells and therefore restricts the
      therapeutic efficacy of anticancer immunotherapy. Here we discuss how the
      metabolic communication between cancer and infiltrating myeloid cells contributes
      to cancer immune evasion and how the understanding of these mechanisms may
      improve current immunotherapies.

PMID- 28499578
TI  - Building a biomimetic membrane for neutron reflectivity investigation:
      Complexity, asymmetry and contrast.
AB  - The preparation and investigation of model membranes is deserving growing
      interest both for the physics of complex systems, and for biology. The need of
      simplified models should preserve mimicking the qualifying characteristics of
      biological membranes, and keep non-invasive and detailed description. As a main
      feature, biological membranes are non-homogeneous in the disposition of
      components, both in the lateral and in the transverse direction. We prepared
      asymmetric supported membranes containing GM1 ganglioside in biomimetic
      proportion according to different protocols. Then, we studied their internal
      structure by neutron reflectometry, providing few-Angstrom sensitivity in the
      cross direction meanwhile avoiding radiation damage. This technique can also be
      profitably applied to study interactions at the membrane surface. The best
      protocol has proven to be the Langmuir-Blodgett/Langmuir-Schaefer depositions.
      Notably, also the simpler and most accessible protocol of vesicle fusion was
      found to be suitable for straightforward and good quality deposition of
      compositionally asymmetric membranes.

PMID- 28499579
TI  - Expression of recombinant truncated domains of mucus-binding (Mub) protein of
      Lactobacillus plantarum in soluble and biologically active form.

PMID- 28499580
TI  - Transient receptor potential (TRP) channels as molecular targets in lung
      toxicology and associated diseases.
AB  - The lungs as the gateways of our body to the external environment are essential
      for gas exchange. They are also exposed to toxicants from two sides, the airways
      and the vasculature. Apart from naturally produced toxic agents, millions of
      human made chemicals were produced since the beginning of the industrial
      revolution whose toxicity still needs to be determined. While the knowledge about
      toxic substances is increasing only slowly, a paradigm shift regarding the
      proposed mechanisms of toxicity at the plasma membrane emerged. According to
      their broad-range chemical reactivity, the mechanism of lung injury evoked by
      these agents has long been described as rather unspecific. Consequently,
      therapeutic options are still restricted to symptomatic treatment. The
      identification of molecular down-stream effectors in cells was a major step
      forward in the mechanistic understanding of the action of toxic chemicals and
      will pave the way for more causal and specific toxicity testing as well as
      therapeutic options. In this context, the involvement of Transient Receptor
      Potential (TRP) channels as chemosensors involved in the detection and effectors
      of toxicant action is an attractive concept intensively discussed in the
      scientific community. In this review we will summarize recent evidence for an
      involvement of TRP channels (TRPA1, TRPC4, TRPC6, TRPV1, TRPV4, TRPM2 and TRPM8)
      expressed in the lung in pathways of toxin sensing and as mediators of lung
      inflammation and associated diseases like asthma, COPD, lung fibrosis and edema
      formation. Specific modulators of these channels may offer new therapeutic
      options in the future and will endorse strategies for a causal, specifically
      tailored treatment based on the mechanistic understanding of molecular events
      induced by lung-toxic agents.

PMID- 28499581
TI  - Defining "mental disorder" in legal contexts.

PMID- 28499582
TI  - Corrigendum to "Interplay between microbial trait dynamics and population
      dynamics revealed by the combination of laboratory experiment and computational
      approaches" [Journal of Theoretical Biology 419 (2017) 201-210].

PMID- 28499584
TI  - Extremely high sulfate reduction, sediment oxygen demand and benthic nutrient
      flux associated with a large-scale artificial dyke and its implication to benthic
      pelagic coupling in the Yeongsan River estuary, Yellow Sea.
AB  - We investigated environmental impact of large-scale dyke on the sediment
      geochemistry, sulfate reduction rates (SRRs), sediment oxygen demand (SOD) and
      potential contribution of benthic nutrient flux (BNF) to primary production in
      the Yeongsan River estuary, Yellow Sea. The sediment near the dyke (YE1) with
      high organic carbon (Corg) content (>4%, dry wt.) was characterized by extremely
      high SOD (327mmolm-2d-1) and SRRs (91-140mmolm-2d-1). The sulfate reduction
      accounted for 73% of Corg oxidation, and was responsible for strikingly high
      concentrations of NH4+ (7.7mM), PO43- (67MUM) and HS- (487MUM) in pore water. The
      BNF at YE1 accounted for approximately 200% of N and P required for primary
      production in the water column. The results present one of the most extreme cases
      that the construction of an artificial dyke may have profound impacts on the
      biogeochemical and ecological processes in coastal ecosystems.

PMID- 28499583
TI  - Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in
      patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international,
      open-label, randomised, controlled, phase 3, multicentre trial.
AB  - BACKGROUND: Previous trials from our group suggested an overall survival benefit
      with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised
      high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference
      in overall survival benefit between three cycles versus five cycles of the same
      neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant
      administration of histotype-tailored regimen to standard chemotherapy. METHODS:
      For this international, open-label, randomised, controlled, phase 3, multicentre
      trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and
      Poland. Eligible patients were aged 18 years or older with localised, high-risk
      (high malignancy grade, 5 cm or longer in diameter, and deeply located according
      to the investing fascia), soft-tissue sarcoma of the extremities or trunk wall
      and belonging to one of five histological subtypes: high-grade myxoid
      liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath
      tumour, and undifferentiated pleomorphic sarcoma. Patients were randomly assigned
      (1:1) to receive three cycles of full-dose standard chemotherapy (epirubicin 60
      mg/m2 per day [short infusion, days 1 and 2] plus ifosfamide 3 g/m2 per day [days
      1, 2, and 3], repeated every 21 days) or histotype-tailored chemotherapy: for
      high-grade myxoid liposarcoma, trabectedin 1.3 mg/m2 via 24-h continuous
      infusion, repeated every 21 days; for leiomyosarcoma, gemcitabine 1800 mg/m2 on
      day 1 intravenously over 180 min plus dacarbazine 500 mg/m2 on day 1
      intravenously over 20 min, repeated every 14 days; for synovial sarcoma, high
      dose ifosfamide 14 g/m2, given over 14 days via an external infusion pump, every
      28 days; for malignant peripheral nerve sheath tumour, intravenous etoposide 150
      mg/m2 per day (days 1, 2, and 3) plus intravenous ifosfamide 3 g/m2 per day (days
      1, 2, and 3), repeated every 21 days; and for undifferentiated pleomorphic
      sarcoma, gemcitabine 900 mg/m2 on days 1 and 8 intravenously over 90 min plus
      docetaxel 75 mg/m2 on day 8 intravenously over 1 h, repeated every 21 days.
      Randomisation was stratified by administration of preoperative radiotherapy and
      by country of enrolment. Computer-generated random lists were prepared by use of
      permuted balanced blocks of size 4 and 6 in random sequence. An internet-based
      randomisation system ensured concealment of the treatment assignment until the
      patient had been registered into the system. No masking of treatment assignments
      was done. The primary endpoint was disease-free survival. The primary and safety
      analyses were planned in the intention-to-treat population. We did yearly
      futility analyses on an intention-to-treat basis. The study was registered with
      ClinicalTrials.gov, number NCT01710176, and with the European Union Drug
      Regulating Authorities Clinical Trials, number EUDRACT 2010-023484-17, and is
      closed to patient entry. FINDINGS: Between May 19, 2011, and May 13, 2016, 287
      patients were randomly assigned to a group (145 to standard chemotherapy and 142
      to histotype-tailored chemotherapy), all of whom, except one patient assigned to
      standard chemotherapy, were included in the efficacy analysis (97 [34%] with
      undifferentiated pleomorphic sarcoma; 64 [22%] with high-grade myxoid
      liposarcoma; 70 [24%] with synovial sarcoma; 27 [9%] with malignant peripheral
      nerve sheath tumour; and 28 [10%] with leiomyosarcoma). At the third futility
      analysis, with a median follow-up of 12.3 months (IQR 2.75-28.20), the projected
      disease-free survival at 46 months was 62% (95% CI 48-77) in the standard
      chemotherapy group and 38% (22-55) in the histotype-tailored chemotherapy group
      (stratified log-rank p=0.004; hazard ratio 2.00, 95% CI 1.22-3.26; p=0.006). The
      most common grade 3 or higher adverse events in the standard chemotherapy group
      (n=125) were neutropenia (107 [86%]), anaemia (24 [19%]), and thrombocytopenia
      (21 [17%]); the most common grade 3 or higher adverse event in the histotype
      tailored chemotherapy group (n=114) was neutropenia (30 [26%]). No treatment
      related deaths were reported in both groups. In agreement with the Independent
      Data Monitoring Committee, the study was closed to patient entry after the third
      futility analysis. INTERPRETATION: In a population of patients with high-risk
      soft-tissue sarcoma, we did not show any benefit of a neoadjuvant histotype
      tailored chemotherapy regimen over the standard chemotherapy regimen. The benefit
      seen with the standard chemotherapy regimen suggests that this benefit might be
      the added value of neoadjuvant chemotherapy itself in patients with high-risk
      soft-tissue sarcoma. FUNDING: European Union grant (Eurosarc FP7 278472).

PMID- 28499586
TI  - [Gemcitabine-induced thrombotic microangiopathy: Can we improve screening and
      treatment?]
AB  - Thrombotic microangiopathy is a rare but severe complication of treatment with
      gemcitabine. Its prevalence increases because gemcitabine's indications are
      growing. We report four cases, which presented with common clinical and
      biological manifestations, i.e. high blood pressure, proteinuria and increasing
      plasmatic creatinine level. However, severity was not similar, hemodialysis was
      inconstant. There is no consensus on treatment for this condition. Stopping
      gemcitabine is essential. Treatment was dispensed considering the severity of the
      presentation: plasma exchange therapy of variable outcome, and eculizumab, which
      was efficient when used. It's important to note that this syndrome includes
      common and frequent signs in patients receiving chemotherapies. But they must
      encourage the research of most specific signs, such as hypertension, mechanic
      hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic
      microangiopathy as early as possible to treat it precociously, and to prevent
      additional gemcitabine injections.

PMID- 28499585
TI  - Multipotent adult progenitor cells improve the hematopoietic function in
      myelodysplasia.
AB  - BACKGROUND AIMS: Myelodysplastic syndromes (MDS) are a group of clonal stem cell
      disorders affecting the normal hematopoietic differentiation process and leading
      to abnormal maturation and differentiation of all blood cell lineages. Treatment
      options are limited, and there is an unmet medical need for effective therapies
      for patients with severe cytopenias. METHODS: We demonstrate that multipotent
      adult progenitor cells (MAPC) improve the function of hematopoietic progenitors
      derived from human MDS bone marrow (BM) by significantly increasing the frequency
      of primitive progenitors as well as the number of myeloid colonies. RESULTS: This
      effect was more pronounced in a non-contact culture, indicating the importance of
      soluble factors produced by the MAPC cells. Moreover, the cells did not stimulate
      the growth of the abnormal MDS clone, as shown by fluorescent in situ
      hybridization analysis on BM cells from patients with a known genetic
      abnormality. We also demonstrate that MAPC cells can provide stromal support for
      patient-derived hematopoietic cells. When MAPC cells were intravenously injected
      into a mouse model of MDS, they migrated to the site of injury and increased the
      hematopoietic function in diseased mice. DISCUSSION: The preclinical studies
      undertaken here indicate an initial proof of concept for the use of MAPC cell
      therapy in patients with MDS-related severe and symptomatic cytopenias and should
      pave the way for further investigation in clinical trials.

PMID- 28499588
TI  - Clinical and molecular characterization of a 13-year-old Indian boy with cutis
      laxa type 2B: Identification of two novel PYCR1 mutations by amplicon-based
      semiconductor exome sequencing.

PMID- 28499587
TI  - The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17
      responses induced by 6-sulfo LacNAc (slan) dendritic cells.
AB  - BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases
      cellular cAMP levels and has proven effective in the treatment of psoriasis and
      psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells
      (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in
      psoriasis with a pronounced capacity to produce proinflammatory cytokines and to
      program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to
      investigate possible immune regulatory effects of the PDE4 inhibitor apremilast
      on slanDCs. METHODS: In vitro studies were performed analyzing the effects of
      apremilast on the proinflammatory function of slanDCs and their capacity to
      induce Th1/Th17-biased T cell responses. RESULTS: Increasing cAMP levels in
      slanDCs by PDE4 inhibition strongly reduced production of IL-12 and TNF-alpha. In
      line with these findings, co-culture experiments with apremilast-pulsed slanDCs
      and allogeneic T cells either from psoriasis patients or healthy controls,
      revealed a significant reduction of IFN-gamma production and expression of the
      transcription factor T-bet. In parallel, production of IL-23 and IL-1beta by
      slanDCs was increased and co-cultured T cells revealed a largely augmented IL-17
      production and an upregulated RORyt expression. CONCLUSIONS: We here demonstrate
      anti-inflammatory as well as Th17-promoting effects of apremilast when studying
      blood precursors of human inflammatory dermal dendritic cells. In the concert of
      the broad anti-inflammatory effects of apremilast on keratinocytes, fibroblasts
      and endothelial cells, the dual effect on slan+ inflammatory dermal DCs should be
      taken into account and may constrain therapeutic responses.

PMID- 28499589
TI  - Askin's Tumor. A Rare Diagnosis in an Elderly Patient.

PMID- 28499590
TI  - MiR-93-5p inhibits the EMT of breast cancer cells via targeting MKL-1 and STAT3.
AB  - Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer
      cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and
      Signal transducer and activator of transcription 3 (STAT3) have been implicated
      in the control of cellular metabolism, survival and growth. Our previous study
      has shown that cooperativity of MKL-1 and STAT3 promoted breast cancer cell
      migration. Herein, we demonstrate a requirement for MKL-1 and STAT3 in miRNA
      mediated cellular EMT to affect breast cancer cell migration. Here we show that
      cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells. Importantly,
      MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box.
      Interestingly, miR-93-5p inhibits the EMT of breast cancer cells through
      suppressing the expression of MKL-1 and STAT3 via targeted their 3'UTR. These
      results demonstrated a novel pathway through which miR-93-5p regulates MKL-1 and
      STAT3 to affect EMT controlling breast cancer cell migration.

PMID- 28499591
TI  - Chronic exposure to dim artificial light at night decreases fecundity and adult
      survival in Drosophila melanogaster.
AB  - The presence of artificial light at night is expanding in geographical range and
      increasing in intensity to such an extent that species living in urban
      environments may never experience natural darkness. The negative ecological
      consequences of artificial night lighting have been identified in several key
      life history traits across multiple taxa (albeit with a strong vertebrate focus);
      comparable data for invertebrates is lacking. In this study, we explored the
      effect of chronic exposure to different night-time lighting intensities on
      growth, reproduction and survival in Drosophila melanogaster. We reared three
      generations of flies under identical daytime light conditions (2600lx) and one of
      four ecologically relevant ALAN treatments (0, 1, 10 or 100lx), then explored
      variation in oviposition, number of eggs produced, juvenile growth and survival
      and adult survival. We found that, in the presence of light at night (1, 10 and
      100lx treatments), the probability of a female commencing oviposition and the
      number of eggs laid was significantly reduced. This did not translate into
      differences at the juvenile phase: juvenile development times and the probability
      of eclosing as an adult were comparable across all treatments. However, we
      demonstrate for the first time a direct link between chronic exposure to light at
      night (greater than 1lx) and adult survival. Our data highlight that ALAN has the
      capacity to cause dramatic shifts in multiple life history traits at both the
      individual and population level. Such shifts are likely to be species-specific,
      however a more in depth understanding of the broad-scale impact of ALAN and the
      relevant mechanisms driving biological change is urgently required as we move
      into an increasing brightly lit future.

PMID- 28499592
TI  - Risk factors for poor outcomes of children with acute acalculous cholecystitis.
AB  - BACKGROUND: Acute acalculous cholecystitis (AAC) is generally considered to be a
      mild disease in children; however, if left untreated or treated without caution,
      AAC can lead to severe outcomes, such as death. The objectives of this study were
      to present the clinical features and identify the predictors of mortality in
      pediatric AAC. METHODS: Patients diagnosed with AAC between 2005 and 2012 were
      enrolled. AAC was defined by the presence of fever and an echo-proven thickened
      gallbladder wall exceeding 4 mm. A poor health outcome was defined as death.
      Further information related to the demographics, clinical manifestations,
      laboratory results, ultrasound findings, and pathogens present in the AAC
      patients was also collected. Predictors of mortality were identified by
      association analyses and confirmed by multivariate logistic regression. RESULTS:
      A total of 147 pediatric AAC patients (male/female = 1.01, mean age = 5.2 years)
      were included in this retrospective study. The most common clinical presentation
      was an elevated C-reactive protein level (84%) followed by hepatomegaly (80%) and
      anorexia (78%). AAC in children was associated with various diseases, including
      infectious diseases (70%), systemic diseases (13%), and malignancy (11%).
      Fourteen of the 147 (9.25%) patients died during the study period. The presences
      of thrombocytopenia, anemia, gallbladder sludge, hepatitis, and/or sepsis plus
      hepatitis were found to be the important predictors of AAC mortality.
      CONCLUSIONS: The factors associated with AAC mortality were anemia,
      thrombocytopenia, gallbladder sludge, hepatitis, and sepsis plus hepatitis. These
      predictors are likely to help clinicians identify patients who are at a high risk
      of poor prognoses and make appropriate clinical decisions.

PMID- 28499593
TI  - Expanding surgical skills and knowledge after training: Lifelong learning puts
      patients first.

PMID- 28499594
TI  - The value of salvage surgery after stereotactic body radiotherapy failure: A
      sticky conundrum.

PMID- 28499595
TI  - Impact of Calcium on Chronic Total Occlusion Percutaneous Coronary Interventions.
AB  - We sought to examine the impact of calcific deposits on the outcomes of chronic
      total occlusion (CTO) percutaneous coronary intervention (PCI). The outcomes of
      1,476 consecutive CTO PCIs performed in 1,453 patients (65.5 +/- 10 years, 85%
      male) between 2012 and 2016 at 11 US centers were evaluated. Moderate or severe
      quantity of calcium was present in 58% of target lesions. Calcified lesions were
      more tortuous and more likely to have proximal cap ambiguity and interventional
      collaterals. PCI of moderately/severely calcified CTOs more often required use of
      the retrograde approach (54% vs 30%, p <0.001) and was associated with longer
      procedure and fluoroscopy time and higher air kerma radiation dose and contrast
      volume. Moderate/severe quantity of calcium was associated with lower technical
      (86.6% vs 93.8%, p <0.001) and procedural (84.4% vs 92.7%, p <0.001) success
      rates and higher incidence of major adverse cardiac events (3.7% vs 1.8%, p =
      0.033). On multivariate analysis, the presence of moderate/severe quantity of
      calcium was not independently associated with technical success. Balloon
      angioplasty was the most common lesion preparation technique for calcified
      lesions, followed by rotational atherectomy and laser. To conclude, in a
      contemporary, multicenter registry, moderate/severe calcific deposits were
      present in 58% of attempted CTO lesions and were associated with higher use of
      the retrograde approach, lower success, and higher complication rates. However,
      on multivariable analysis, the amount of calcium was not independently associated
      with technical success.

PMID- 28499596
TI  - Magnetic porous beta-cyclodextrin polymer for magnetic solid-phase extraction of
      microcystins from environmental water samples.
AB  - Microcystins (MCs) are cyclic heptapeptide toxins and tumor promoters produced by
      cyanobacteria, which threaten the health of humans. In this study, magnetic
      porous beta-cyclodextrin polymer (Fe3O4@SiO2@P-CDP) was synthesized and
      characterized by transmission electron microscopy, scanning electron microscopy,
      energy dispersive X-ray spectrometry, Fourier transform infrared spectrometry, X
      ray diffraction, nitrogen adsorption porosimetry and vibrating sample
      magnetometer. The synthesized Fe3O4@SiO2@P-CDP particles were then used for
      magnetic solid-phase extraction (MSPE) of MCs from environmental water samples,
      and exhibited excellent extraction performance, especially for MC-RR. Coupled
      with high-performance liquid chromatography with tandem mass spectrometry (HPLC
      MS/MS), a simple, efficient and sensitive method for determination of trace
      levels of MCs was established. After the optimization of conditions, wide linear
      ranges (2.0-1000pgmL-1), good linearity (r2>=0.9996) and acceptable repeatability
      (RSD<=9.4%, n=5) were obtained. The limits of detection (LODs, S/N=3) and limits
      of quantification (LOQs, S/N=10) for three MCs (MC-LR, MC-RR and MC-YR) were in
      the range of 1.0-2.0pgmL-1 and 2.0-5.0pgmL-1, respectively. Typical water samples
      were analyzed by the developed method, and trace levels of MC-LR and MC-RR were
      detected. The results demonstrate that the developed method has great potential
      for the determination of MCs in complicated matrix.

PMID- 28499597
TI  - Effect of cationic monomer content on polyacrylamide copolymers by frit-inlet
      asymmetrical flow field-flow fractionation/multi-angle light scattering.
AB  - In this study, ultrahigh-molecular-weight (MW) (>107Da) cationic polyacrylamides
      (C-PAMs), which are water-soluble polymers used in waste water treatment, were
      characterized using frit-inlet asymmetrical flow field-flow fractionation coupled
      with multi-angle light scattering and differential refractive detection. C-PAMs
      copolymerized with acryloxyethyltrimethyl ammonium chloride (DAC) were prepared
      by varying the feed amount of cationic monomer, polymerization method (solution
      vs. emulsion), and degree of branching. The MW of the copolymers prepared using
      emulsion polymerization (107-109Da) was generally larger than that of copolymers
      prepared using solution polymerization (4*107-108Da). When the amount of cationic
      monomer was increased from 10 to 55mol% in solution polymerization, hydrophobic
      contraction of the core induced formation of more compact C-PAMs. The copolymers
      prepared using emulsion polymerization formed highly aggregated or supercoil
      structures owing to increased intermolecular hydrophobic interaction when less
      cationic monomer was used. However, the MW decreased with increased cationic
      group content. In addition, C-PAMs larger than ~108Da prepared using the emulsion
      method were separated by steric/hyperlayer elution mode while those in the 107
      108Da range were analyzed in either normal or steric/hyperlayer mode depending on
      the decay patterns of field programming. Moreover, branched copolymers were found
      to be resolved with different elution modes under the same field decay pattern
      depending on the degree of branching: steric/hyperlayer for low-branching and
      normal for high-branching C-PAMs.

PMID- 28499598
TI  - Simultaneous electromembrane extraction of cationic and anionic herbicides across
      hollow polymer inclusion membranes with a bubbleless electrode.
AB  - A new electric-field driven extraction approach based on the integration of a
      bubbleless electrode into the electromembrane extraction (EME) across hollow
      polymer inclusion membranes (HPIMs) was demonstrated for the first time. The
      bubbleless electrode was prepared based on an in-situ synthesised polyacrylamide
      within a fused silica capillary. The electrode functions as a salt bridge, which
      conducts the electrical current between the acceptor phase in the lumen of the
      HPIM and the acceptor solution in the reservoir connected to a high voltage
      supply through a platinum electrode. Two types of HPIMs were employed, which
      consisted of desired proportions of cellulose acetate as base polymer, tris(2
      ethylhexyl)phosphate as plasticizer, and di-(2-ethylhexyl)phosphoric acid as
      anionic carrier or Aliquat 336 as cationic carrier, respectively. The EME
      strategy was evaluated for the simultaneous determination of cationic quaternary
      ammonium and anionic chlorophenoxy acetic acid herbicides present in the river
      water, respectively. The analysis was carried out using capillary electrophoresis
      coupled with UV and contactless conductivity detection. Under the optimised
      conditions, enrichment factors in the range of 152-185-fold were obtained from
      4mL of river water sample with a 20min extraction time and an applied voltage of
      3000V. The proposed method provided good linearity with correlation coefficients
      ranging from 0.9982 to 0.9997 over a concentration range of 1-1000MUg/L. The
      detection limits of the method for the herbicides were in the range of 0.3
      0.4MUg/L, with relative standard deviations of between 4.8% and 8.5%. The
      relative recoveries obtained when analysing the spiked river water ranged from
      99.1% to 100%. A comparison was also made between the newly developed approach
      with the conventional EME setup by placing the platinum electrode directly in the
      lumen of the HPIMs.

PMID- 28499599
TI  - Gas chromatography - mass spectrometry data processing made easy.
AB  - Evaluation of GC-MS data may be challenging due to the high complexity of data
      including overlapped, embedded, retention time shifted and low S/N ratio peaks.
      In this work, we demonstrate a new approach, PARAFAC2 based Deconvolution and
      Identification System (PARADISe), for processing raw GC-MS data. PARADISe is a
      computer platform independent freely available software incorporating a number of
      newly developed algorithms in a coherent framework. It offers a solution for
      analysts dealing with complex chromatographic data. It allows extraction of
      chemical/metabolite information directly from the raw data. Using PARADISe
      requires only few inputs from the analyst to process GC-MS data and subsequently
      converts raw netCDF data files into a compiled peak table. Furthermore, the
      method is generally robust towards minor variations in the input parameters. The
      method automatically performs peak identification based on deconvoluted mass
      spectra using integrated NIST search engine and generates an identification
      report. In this paper, we compare PARADISe with AMDIS and ChromaTOF in terms of
      peak quantification and show that PARADISe is more robust to user-defined
      settings and that these are easier (and much fewer) to set. PARADISe is based on
      non-proprietary scientifically evaluated approaches and we here show that
      PARADISe can handle more overlapping signals, lower signal-to-noise peaks and do
      so in a manner that requires only about an hours worth of work regardless of the
      number of samples. We also show that there are no non-detects in PARADISe,
      meaning that all compounds are detected in all samples.

PMID- 28499600
TI  - Lipid vesicles in pulsed electric fields: Fundamental principles of the membrane
      response and its biomedical applications.
AB  - The present review focuses on the effects of pulsed electric fields on lipid
      vesicles ranging from giant unilamellar vesicles (GUVs) to small unilamellar
      vesicles (SUVs), from both fundamental and applicative perspectives. Lipid
      vesicles are the most popular model membrane systems for studying biophysical and
      biological processes in living cells. Furthermore, as vesicles are made from
      biocompatible and biodegradable materials, they provide a strategy to create safe
      and functionalized drug delivery systems in health-care applications. Exposure of
      lipid vesicles to pulsed electric fields is a common physical method to
      transiently increase the permeability of the lipid membrane. This method, termed
      electroporation, has shown many advantages for delivering exogenous molecules
      including drugs and genetic material into vesicles and living cells. In addition,
      electroporation can be applied to induce fusion between vesicles and/or cells.
      First, we discuss in detail how research on cell-size GUVs as model cell systems
      has provided novel insight into the basic mechanisms of cell electroporation and
      associated phenomena. Afterwards, we continue with a thorough overview how
      electroporation and electrofusion have been used as versatile methods to
      manipulate vesicles of all sizes in different biomedical applications. We
      conclude by summarizing the open questions in the field of electroporation and
      possible future directions for vesicles in the biomedical field.

PMID- 28499601
TI  - Multicomponent nanocrystals with anti-Stokes luminescence as contrast agents for
      modern imaging techniques.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) have recently attracted great
      attention in theranostics due to their exceptional optical and physicochemical
      properties, which enable the design of a novel UCNP-based nanoplatform for
      luminescent imaging, temperature mapping, sensing, and therapy. In addition,
      UCNPs are considered to be ideal building blocks for development of multimodal
      probes for cells and whole body imaging, exploiting simple variation of host
      matrix, dopant ions, and surface chemistry. Modalities responsible for magnetic
      resonance imaging (MRI), computed tomography (CT), and positron emission
      tomography (PET)/single-photon emission computed tomography (SPECT) are embedded
      in a single UC nanocrystal, providing integrating effect over any modality alone
      in terms of the efficiency and sensitivity for clinical innovative diagnosis
      through multimodal bioimaging. In particular, we demonstrate applications of
      UCNPs as a new nanoplatform for optical and multimodal cancer imaging in vitro
      and in vivo and extend discussions to delivery of UCNP-based therapeutic agents
      for photodynamic and photothermal cancer treatments.

PMID- 28499602
TI  - From polyelectrolyte complexes to polyelectrolyte multilayers: Electrostatic
      assembly, nanostructure, dynamics, and functional properties.
AB  - Polyelectrolyte complexes (PECs) are three-dimensional macromolecular structures
      formed by association of oppositely charged polyelectrolytes in solution.
      Polyelectrolyte multilayers (PEMs) can be considered a special case of PECs
      prepared by layer-by-layer (LbL) assembly that involves sequential deposition of
      molecular-thick polyelectrolyte layers with nanoscale control over the size,
      shape, composition and internal organization. Although many functional PEMs with
      novel physical and chemical characteristics have been developed, the current
      practical applications of PEMs are limited to those that require only a few
      bilayers and are relatively easy to prepare. The viability of such engineered
      materials can be realized only after overcoming the scientific and engineering
      challenges of understanding the kinetics and transport phenomena involved in the
      multilayer growth and the factors governing their final structure, composition,
      and response to external stimuli. There is a great need to model PEMs and to
      connect PEM behavior with the characteristics of the PEC counterparts to allow
      for prediction of performance and better design of multilayered materials. This
      review focuses on the relationship between PEMs and PECs. The constitutive
      interactions, the thermodynamics and kinetics of polyelectrolyte complexation and
      PEM formation, PEC phase behavior, PEM growth, the internal structure and
      stability in PEMs and PECs, and their response to external stimuli are presented.
      Knowledge of such interactions and behavior can guide rapid fabrication of PEMs
      and can aid their applications as nanocomposites, coatings, nano-sized reactors,
      capsules, drug delivery systems, and in electrochemical and sensing devices. The
      challenges and opportunities in future research directions are also discussed.

PMID- 28499603
TI  - Bio-templated silica composites for next-generation biomedical applications.
AB  - Silica-based materials have extensive biomedical applications owing to their
      unique physical, chemical, and biological properties. Recently, increasing
      studies have examined the mechanisms involved in biosilicification to develop
      novel, fine-tunable, eco-friendly materials and/or technologies. In this review,
      we focus on recent developments in bio-templated silica synthesis and relevant
      applications in drug delivery systems, tissue engineering, and biosensing.

PMID- 28499604
TI  - Iron oxide nanoparticles - In vivo/in vitro biomedical applications and in silico
      studies.
AB  - The review presents a broad overview of the biomedical applications of surface
      functionalized iron oxide nanoparticles (IONPs) as magnetic resonance imaging
      (MRI) agents for sensitive and precise diagnosis tool and synergistic combination
      with other imaging modalities. Then, the recent progress in therapeutic
      applications, such as hyperthermia is discussed and the available toxicity data
      of magnetic nanoparticles concerning in vitro and in vivo biomedical applications
      are addressed. This review also presents the available computer models using
      molecular dynamics (MD), Monte Carlo (MC) and density functional theory (DFT), as
      a basis for a complete understanding of the behaviour and morphology of
      functionalized IONPs, for improving NPs surface design and expanding the
      potential applications in nanomedicine.

PMID- 28499605
TI  - Interfacial characteristics of binary polymer blend films spread at the air-water
      interface.
AB  - The interfacial characteristics of binary polymer blend films spread at the air
      water interface are reviewed, focusing on their surface pressures, interfacial
      structures, and dilational moduli as a function of the miscibility. Miscible
      polymer blend films show thermodynamic, structural, and dynamic properties which
      are a combination of those from both components in the polymer blend present at
      the air-water interface. No preferential adsorption is observed and the behavior
      does not depend on the surface concentration regime. In contrast, for immiscible
      polymer blend films, preferential adsorption of one polymer phase occurs at the
      air-water interface and the interfacial characteristics in the semi-dilute and
      concentrated regimes are strongly controlled by one of the components of the
      adsorbed polymer.

PMID- 28499606
TI  - Finite element analysis of stress extent at peri-implant bone surrounding
      external hexagon or Morse taper implants.
AB  - PURPOSE: The purpose of the present study was to evaluate the distribution of
      stresses and consequent bone volume affected surrounding external hexagon or
      Morse taper dental implant systems by finite element analysis. MATERIAL AND
      METHODS: Two different dental implant-abutment designs were assessed: external
      hexagon or Morse taper joints. A mandibular bone model obtained from a computed
      tomography scan was used. The implant-abutment systems were axially or obliquely
      (45 degrees ) loaded on 150 N relatively to the central axis of the implant. The
      von Mises stresses were analysed in terms of magnitude and volume of affected
      surrounding bone. RESULTS: The von Mises equivalent values found on the cortical
      bone were higher than that recorded on the trabecular bone. Additionally, the
      bone volume associated with high stress values was higher in cortical and
      trabecular bone for oblique loading compared to axial loading. The values of von
      Mises equivalent stress around Morse taper implant-abutment system were lower on
      both axial and oblique loads than those recorded for external hexagon implant
      abutment systems. CONCLUSIONS: Morse taper implant joints revealed a proper
      biomechanical behavior when compared to external hexagon systems concerning a
      significant volume of surrounding peri-implant bone subjected to lower stresses
      values.

PMID- 28499608
TI  - Fat or fit: The big oxymoron of (metabolically) healthy obesity.

PMID- 28499607
TI  - Evaluation of intensity modulated radiation therapy dose painting for localized
      prostate cancer using 68Ga-HBED-CC PSMA-PET/CT: A planning study based on
      histopathology reference.
AB  - PURPOSE: To demonstrate the feasibility and to evaluate the tumour control
      probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose
      painting using 68Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer
      (PCa). METHODS AND MATERIALS: 10 patients had PSMA PET/CT scans prior to
      prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of
      30%. Two IMRT plans were generated for each patient: Plan77 which consisted of
      whole-prostate IMRT to 77Gy, and Plan95 which consisted of whole-prostate IMRT to
      77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35
      fractions). The feasibility of these plans was judged by their ability to adhere
      to the FLAME trial protocol. TCP-histo/-PET were calculated on co-registered
      histology (GTV-histo) and GTV-PET, respectively. NTCPs for rectum and bladder
      were calculated. RESULTS: All plans reached prescription doses whilst adhering to
      dose constraints. In Plan77 and Plan95 mean doses in GTV-histo were 75.8+/-0.3Gy
      and 96.9+/-1Gy, respectively. Average TCP-histo values for Plan77 and Plan95 were
      70% (range: 15-97%), and 96% (range: 78-100%, p<0.0001). Average TCP-PET values
      for Plan77 and Plan95 were 55% (range: 27-82%), and 100% (range: 99-100%,
      p<0.0001). There was no significant difference between TCP-PET and TCP-histo in
      Plan95 (p=0.25). There were no significant differences in rectal (p=0.563) and
      bladder (p=0.3) NTCPs. CONCLUSIONS: IMRT dose painting using PSMA PET/CT was
      technically feasible and resulted in significantly higher TCPs without higher
      NTCPs.

PMID- 28499609
TI  - Achilles tendon xanthomas are associated with the presence and burden of
      subclinical coronary atherosclerosis in heterozygous familial
      hypercholesterolemia: A pilot study.
AB  - BACKGROUND AND AIMS: Achilles tendon xanthomas (ATX) are a sign of long-term
      exposure to high blood cholesterol in familial hypercholesterolemia (FH)
      patients, which have been associated with cardiovascular disease. We evaluated
      the ATX association with the presence and extent of subclinical coronary
      atherosclerosis in heterozygous FH patients. METHODS: 102 FH patients diagnosed
      by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279
      mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease,
      underwent computed tomography angiography and coronary artery calcium (CAC)
      quantification. Subclinical coronary atherosclerosis was quantified by CAC,
      segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson
      regression was used to assess the association of ATX with subclinical
      atherosclerosis burden as continuous variables. RESULTS: Patients with ATX (n =
      21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as
      greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex,
      smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a)
      concentrations, there was an independent positive association of ATX presence
      with CAC scores (beta = 1.017, p < 0.001), SSS (beta = 0.809, p < 0.001) and SIS
      (beta = 0.640, p < 0.001). CONCLUSIONS: ATX are independently associated with the
      extension of subclinical coronary atherosclerosis quantified by tomographic
      scores in FH patients.

PMID- 28499610
TI  - Effects of cyanobacteria Oscillatoria sp. lipopolysaccharide on B cell activation
      and Toll-like receptor 4 signaling.
AB  - Cyanobacteria ("blue-green algae"), such as Oscillatoria sp., are a ubiquitous
      group of bacteria found in freshwater systems worldwide that are linked to
      illness and in some cases, death among humans and animals. Exposure to
      cyanobacteria occurs via ingestion of contaminated water or food-products.
      Exposure of the gut to these bacteria also exposes their toxins, such as
      lipopolysaccharide (LPS), to B cells in the gut associated lymphoid tissue.
      However, the effect of Oscillatoria sp. LPS on B cell activation is unknown. To
      test the hypothesis that Oscillatoria sp. LPS exposure to murine B cells would
      result in B cell activation, murine B cells were incubated in the absence or
      presence of Oscillatoria sp. LPS or E. coli LPS as a positive control. The data
      indicate that Oscillatoria sp. LPS induces B cells to proliferate, upregulate MHC
      II and CD86, enhance antigen uptake and induce IgM production at low levels.
      Additional studies demonstrate that this low level of stimulation may be due to
      incomplete TLR4 signaling induced by Oscillatoria sp. LPS, since IRF-3 is not
      induced in B cells after stimulation with Oscillatoria sp. LPS. These findings
      have important implications for the mechanisms of toxicity of cyanobacteria in
      both humans and animals.

PMID- 28499611
TI  - Silver nanoparticle-induced phosphorylation of histone H3 at serine 10 is due to
      dynamic changes in actin filaments and the activation of Aurora kinases.
AB  - The phosphorylation of histone H3 at serine 10 (p-H3S10) has been closely
      correlated with mitotic chromosome condensation. We previously reported that
      silver nanoparticles (AgNPs) significantly induced p-H3S10 independent of
      mitosis. In the present study, we examined the mechanisms underlying the
      induction of p-H3S10 by AgNPs. A treatment with AgNPs markedly induced p-H3S10 in
      a dose-dependent manner in three types of cell lines, and this was dependent on
      the cellular incorporation of AgNPs. The immunofluorescent staining of AgNP
      induced p-H3S10 was thin and solid throughout the nucleus, and differed from that
      normally associated with mitosis. AgNPs induced the formation of globular actin
      in a dose-dependent manner. Latrunculin B (LatB) and phalloidin, inhibitors of
      actin polymerization and depolymerization, respectively, inhibited p-H3S10,
      suggesting that dynamic changes in actin filaments are related to AgNP-induced p
      H3S10. Furthermore, p-H3S10 was mediated by Aurora kinase (AURK) pathways, which
      were suppressed by LatB and siRNA for cofilin 1, an actin-depolymerizing protein.
      AgNO3 (Ag ions) exerted similar effects to those of AgNPs. These results suggest
      that Ag ions released from AgNPs incorporated into inner cells changed the
      dynamics of actin filaments, and this was followed by the activation of AURKs,
      leading to the induction of p-H3S10.

PMID- 28499612
TI  - Environmentally relevant dose of arsenic interferes in functions of human
      monocytes derived dendritic cells.
AB  - Arsenic is a major environmental pollutant and highly hazardous toxin to human
      health, which well established as carcinogen and immune deregulatory properties.
      Dendritic cells (DCs) have a pivotal role in cell-mediated immunity for T-cell
      activation and antigen presentation. In this study, T cell activation, some key
      functional genes expression, cell stability and phagocytosis capacity of human
      monocytes derived DCs (MDDCs) were analyzed after in vitro exposure to very low
      dose of arsenic for 12 and 24h. Arsenic decreased continually phagocytosis
      capacity of MDDCs. Furthermore, down-regulation of the cell-surface expression of
      the co-stimulatory molecule CD40 after 24h post treatment with arsenic, confirmed
      arsenic interferers in the phagocytosis process. Pro inflammatory cytokines,
      IL1beta and TNFalpha were more expressed in arsenic-treated MDDCs while IL6
      transiently was down regulated. In general, our novel findings here strongly
      suggest that low level of arsenic dysregulates four fundamental immune processes
      of DCs. Mechanistically; this could explain the observed immunodeficiency
      activity of Arsenic, and give direction for comprehension the pathogenesis of
      Arsenic-induced diseases.

PMID- 28499615
TI  - Why did arterial pressure not increase after fluid administration?

PMID- 28499614
TI  - Considerations on the low adherence to clinical practice guidelines.

PMID- 28499613
TI  - Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR
      Sprague-Dawley rat: A CLARITY-BPA study.
AB  - The goal of this study was to determine whether bisphenol A (BPA) had adverse
      effects indicative of cardiac toxicity. As part of the "Consortium Linking
      Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA), study dams and
      offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to
      25000MUg/kg/day, 0.05 or 0.5MUg/kg/day 17alpha-ethinyl-estradiol (EE) or 0.3%
      carboxymethylcellulose vehicle. Exposure-related effects were analyzed in
      isolated hearts by quantitative morphometry and histopathology. No dose-related
      changes in body weight were detected. Across all exposure groups including
      vehicle controls, body weight of continuously dosed males was reduced compared to
      males dosed only until PND21. Heart weight was increased only in females exposed
      to EE, and consistent alterations in LV wall thickness were not observed.
      Exposure-related changes in collagen accumulation were minor and limited to
      highest EE exposure groups with increased collagen accumulation in PND21 males.
      Decreased collagen was observed in hearts of BPA or EE exposed females at PND90
      and PND180. In BPA or EE treated females cardiomyopathy incidence and severity
      was significantly increased compared to control females at PND21 with myocardial
      degeneration observed in both males and females at PND21 and PND90.

PMID- 28499617
TI  - Community-based Outcomes of Open versus Robot-assisted Radical Prostatectomy.
AB  - BACKGROUND: Identifying the optimal surgical approach for patients with localized
      prostate cancer (PCa) managed in the community setting remains controversial due
      to the lack of robust, prospective data. OBJECTIVE: To assess surgical outcomes
      and changes in urinary and sexual quality of life (QOL) over time in patients
      undergoing radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: Our
      study included patients enrolled in Cancer of the Prostate Strategic Urologic
      Research Endeavor (CaPSURE), a large, prospective, mostly community-based,
      nationwide PCa registry, who underwent RP between 2004 and 2016. INTERVENTION:
      Open (ORP) versus robot-assisted radical prostatectomy (RARP) for localized PCa.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic and clinicopathologic
      data and surgical outcomes were compared between ORP and RARP. Self-reported,
      validated questionnaires (scaled 0-100 with higher numbers indicating better
      function) were used to evaluate urinary and sexual QOL at different time points.
      Repeated measures mixed-models assessed changes in function and bother over time
      in each domain. RESULTS AND LIMITATIONS: Among 1892 men (n = 1137 ORP; n = 755
      RARP), Cancer of the Prostate Risk Assessment score, Gleason grade at biopsy and
      RP, and pT-stage were lower in ORP patients (all p < 0.01). Men undergoing RARP
      had comparable surgical margin rates, lymph node yields, and biochemical
      recurrence rates. In a subset analysis with 1451 men reporting baseline and
      follow-up QOL data, ORP patients reported superior scores in urinary incontinence
      (ORP mean +/- standard deviation 69 +/- 26 vs RARP 62 +/- 27) and bother (ORP
      75+/-29 vs RARP 68+/-28, both p < 0.01) only in the 1st yr after RP. Differences
      in sexual outcomes did not differ between groups, nor did any QOL scores beyond 1
      yr. Limitations include a decrease in the rate of questionnaire response during
      follow-up, potential selection biases in terms of patient assignment to ORP
      versus RARP and survey completion rates, and the fact that RARP cases likely
      included the initial learning curve for the CaPSURE surgeons. CONCLUSIONS: Most
      patients experienced changes in urinary and sexual QOL in the 1st 3 yr following
      RP. The pattern of recovery over time was similar between ORP and RARP groups.
      Patients should not expect different oncologic or QOL outcomes based on surgical
      approach. PATIENT SUMMARY: Aside from a small, early, and temporary advantage in
      terms of urinary incontinence and bother favoring open surgery, minimal
      differences in outcomes are observed when comparing men who undergo open versus
      robot-assisted prostatectomy in the community setting.

PMID- 28499616
TI  - Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart
      toxicity in Wistar rats.
AB  - Tramadol and tapentadol are extensively prescribed for the treatment of moderate
      to severe pain. Although these drugs are very effective in pain treatment, the
      number of intoxications and deaths due to both opioids is increasing, and the
      underlying toxic mechanisms are not fully understood. The present work aimed to
      study the potential biochemical and histopathological alterations induced by
      acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats.
      Forty-two male Wistar rats were divided into different groups: a control,
      administered with normal saline solution, and tramadol- or tapentadol-treated
      groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and
      maximum recommended doses, respectively). 24h after intraperitoneal
      administration, biochemical and oxidative stress analyses were performed in
      blood, and specimens from brain, lung and heart were taken for histopathological
      and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio,
      in LDH, CK and CK-MB activities in serum samples, and an increase in lactate
      levels in serum and brain samples. Oxidative damage, namely protein oxidation,
      was found in heart and lung tissues. In histological analyses, tramadol and
      tapentadol were found to cause alterations in cell morphology, inflammatory cell
      infiltrates and cell death in all tissues under study, although tapentadol caused
      more damage than tramadol. Our results confirmed the risks of tramadol exposure,
      and demonstrated the higher risk of tapentadol, especially at high doses.

PMID- 28499618
TI  - Applying Precision Oncology to Renal Cell Carcinoma: Emerging Challenges.

PMID- 28499619
TI  - Reply to Tuomas Mirtti and Tero Aittokallio's Letter to the Editor re: Fatemeh
      Seyednasrollah, Mehrad Mahmoudian, Liisa Rautakorpi, et al. How Reliable are
      Trial-based Prognostic Models in Real-world Patients with Metastatic Castration
      resistant Prostate Cancer? Eur Urol. 2017;71:838-40. Clinical Utility of Trial
      estimated Prognostic Models.

PMID- 28499620
TI  - Re: Fatemeh Seyednasrollah, Mehrad Mahmoudian, Liisa Rautakorpi, et al. How
      Reliable are Trial-based Prognostic Models in Real-world Patients with Metastatic
      Castration-resistant Prostate Cancer? Eur Urol. 2017;71:838-40.

PMID- 28499621
TI  - An adaptive positivity thresholding method for automated Ki67 hotspot detection
      (AKHoD) in breast cancer biopsies.
AB  - The proliferative activity of breast cancer tissue can be estimated using the
      Ki67 biomarker. The percentage of positivity of such biomarker is correlated with
      proliferation and consequently with the prognosis of a breast tumor. Ki67 marked
      tissue samples are analyzed by an experienced pathologist who identifies the most
      active areas of tumor cell proliferation called hotspots, and estimates the
      positivity of each case. A method for the Automated Ki67 Hotspot Detection
      (AKHoD) is presented in this work. The main objective of the AKHoD method is to
      automatically and efficiently provide the pathologist with suggestions about Ki67
      hotspot areas as a decision support. The input of AKHoD is a digital slide that
      is divided in tiles. For each tile, AKHoD provides a rough estimate of positivity
      and cellularity, summarized in very low resolution positivity and cellularity
      images. In a second step, an adaptive thresholding is applied to such positivity
      image to identify the most positive connected and convex areas, within
      cellularity limits set by current guidelines (that is, 500-2000). The method has
      been preliminarily validated on 50 digital slides for which three expert
      pathologists provided gold standard hotspots. 82% of the gold standard hotspots
      have been successfully recognized by the system, spending an average of 54s per
      slide. While further validation is needed taking into account also patients
      follow-up, this first experimentation suggests that the proposed method could be
      adequate for supporting the pathologist in hotspot detection.

PMID- 28499622
TI  - m6A in mRNA: An Ancient Mechanism for Fine-Tuning Gene Expression.
AB  - Modifications in mRNA constitute ancient mechanisms to regulate gene expression
      post-transcriptionally. N6-methyladenosine (m6A) is the most prominent mRNA
      modification, and is installed by a large methyltransferase complex (the m6A
      'writer'), not only specifically bound by RNA-binding proteins (the m6A
      'readers'), but also removed by demethylases (the m6A 'erasers'). m6A mRNA
      modifications have been linked to regulation at multiple steps in mRNA
      processing. In analogy to the regulation of gene expression by miRNAs, we propose
      that the main function of m6A is post-transcriptional fine-tuning of gene
      expression. In contrast to miRNA regulation, which mostly reduces gene
      expression, we argue that m6A provides a fast mean to post-transcriptionally
      maximize gene expression. Additionally, m6A appears to have a second function
      during developmental transitions by targeting m6A-marked transcripts for
      degradation.

PMID- 28499623
TI  - Response to Letter to the Editor on "Long-Term Results of Total Hip Arthroplasty
      With Shortening Subtrochanteric Osteotomy in Crowe IV Developmental Dysplasia".

PMID- 28499624
TI  - Acetabular Placement Accuracy With the Direct Anterior Approach Freehand
      Technique.
AB  - BACKGROUND: Acetabular cup placement in total hip arthroplasty (THA) has been
      recognized as an important factor in operative success, and accurate cup
      placement has been the impetus for novel medical technologies. METHODS: This
      article examines the cup placement in 955 THAs using a freehand Direct Anterior
      Approach on a standard operating table. Acetabular anteversion and inclination
      were determined using the circle theorem. Measurements were divided into safe
      zone placement determined by Callanan et al as 5 degrees -25 degrees  for
      anteversion and 30 degrees -45 degrees  for inclination, as well as by Lewinnek
      et al as 5 degrees -25 degrees  for anteversion and 30 degrees -50 degrees  for
      inclination. Dislocation rate was determined and correlated to safe zone
      placement. RESULTS: Although technology has advanced for cup placement, this
      investigation shows that a freehand technique demonstrates 0.31% dislocation
      after THA with an accuracy of 85% for the Lewinnek safe zone and 61% for
      Callanan, potentially because of the sparing of the posterior hip capsule.
      CONCLUSION: The direct anterior approach to the hip on a regular operating table
      is safe and reliable. Our results demonstrate improvement in cup positioning
      compared with other freehand techniques. Surgeon awareness and control of the
      position of the pelvis within space optimizes acetabular component accuracy and
      precision without the need for special equipment, such as intraoperative
      fluoroscopy.

PMID- 28499625
TI  - Range of Motion Simulation of Hip Joint Movement During Salat Activity.
AB  - BACKGROUND: Impingement of an artificial hip joint because of limited range of
      motion (RoM) during human activity is one of the main sources of hip joint
      failure. The aim of this article is to simulate the RoMs of hip joints during
      salat, the practice of formal worship in Islam. METHODS: Salat consists of
      several stages which can be represented with a cycle (raka'ah). Every raka'ah
      consists of standing, bowing (ruku'), straightening up (i'tidal), transition of
      standing toward prostrating, prostrating (sujud), and sitting. A virtual skeleton
      model was used to analyze the motion during salat for the possibility of the
      impingement occurrence. RESULTS: The results of the simulation were presented in
      terms of maximum flexion, abduction, and internal or external rotation. The
      results also showed that the prostration position is similar in RoM with the
      Japanese zarei position and similar in RoM to pick up an object while sitting on
      a chair. CONCLUSION: Specific aspects of salat such as the difference in position
      of the 2 legs at the last sitting position create an extreme RoM which in turn
      results in a high risk of impingement.

PMID- 28499626
TI  - Carbon Dioxide Exposure Resulting From Hood Protective Equipment Used in Joint
      Arthroplasty Surgery.
AB  - BACKGROUND: To protect both the surgeon and patient during procedures, hooded
      protection shields are used during joint arthroplasty procedures. Headache,
      malaise, and dizziness, consistent with increased carbon dioxide (CO2) exposure,
      have been anecdotally reported by surgeons using hoods. We hypothesized that
      increased CO2 concentrations were causing reported symptoms. METHODS: Six healthy
      subjects (4 men) donned hooded protection, fan at the highest setting. Arm cycle
      ergometry at workloads of 12 and 25 watts (W) simulated workloads encountered
      during arthroplasty. Inspired O2 and CO2 concentrations at the nares were
      continuously measured at rest, 12 W, and 25 W. At each activity level, the fan
      was deactivated and the times for CO2 to reach 0.5% and 1.0% were measured.
      RESULTS: At rest, inspired CO2 was 0.14% +/- 0.04%. Exercise had significant
      effect on CO2 compared with rest (0.26% +/- 0.08% at 12 W, P = .04; 0.31% +/-
      0.05% at 25 W, P = .003). Inspired CO2 concentration increased rapidly with fan
      deactivation, with the time for CO2 to increase to 0.5% and 1.0% after fan
      deactivation being rapid but variable (0.5%, 12 +/- 9 seconds; 1%, 26 +/- 15
      seconds). Time for CO2 to return below 0.5% after fan reactivation was 20 +/- 37
      seconds. CONCLUSION: During simulated joint arthroplasty, CO2 remained within
      Occupational Safety and Health Administration (OSHA) standards with the fan at
      the highest setting. With fan deactivation, CO2 concentration rapidly exceeds
      OSHA standards.

PMID- 28499627
TI  - Clinical application of MOSkin dosimeters to rectal wall in vivo dosimetry in
      gynecological HDR brachytherapy.
AB  - PURPOSE: Three MOSkins dosimeters were assembled over a rectal probe and used to
      perform in vivo dosimetry during HDR brachytherapy treatments of vaginal cancer.
      The purpose of this study was to verify the applicability of the developed tool
      to evaluate discrepancies between planned and measured doses to the rectal wall.
      MATERIALS AND METHODS: MOSkin dosimeters from the Centre for Medical Radiation
      Physics are particularly suitable for brachytherapy procedures for their ability
      to be easily incorporated into treatment instrumentation. In this study, 26
      treatment sessions of HDR vaginal brachytherapy were monitored using three MOSkin
      mounted on a rectal probe. A total of 78 measurements were collected and compared
      to doses determined by the treatment planning system. RESULTS: Mean dose
      discrepancy was determined as 2.2+/-6.9%, with 44.6% of the measurements within
      +/-5%, 89.2% within +/-10% and 10.8% higher than +/-10%. When dose discrepancies
      were grouped according to the time elapsed between imaging and treatment (i.e.,
      group 1: <=90min; group 2: >90min), mean discrepancies resulted in 4.7+/-3.6% and
      7.1+/-5.0% for groups 1 and 2, respectively. Furthermore, the position of the
      dosimeter on the rectal catheter was found to affect uncertainty, where highest
      uncertainties were observed for the dosimeter furthest inside the rectum.
      CONCLUSIONS: This study has verified MOSkin applicability to in-patient dose
      monitoring in gynecological brachytherapy procedures, demonstrating the
      dosimetric rectal probe setup as an accurate and convenient IVD instrument for
      rectal wall dose verification. Furthermore, the study demonstrates that the
      delivered dose discrepancy may be affected by the duration of treatment planning.

PMID- 28499628
TI  - A real world wearable cardioverter defibrillator experience - Very high
      appropriate shock rate in ischemic cardiomyopathy patients at a European single
      center.
AB  - BACKGROUND: The wearable cardioverter defibrillator (WCD) has emerged as a
      valuable tool to protect patients with increased risk of sudden cardiac death
      (SCD). We sought to characterize WCD patients and to analyze predictors of
      ventricular arrhythmia (VA) occurrence and WCD shock delivery. METHODS AND
      RESULTS: One hundred fourteen patients with WCD use were included in the study.
      Indications were mainly ischemic cardiomyopathy (ICM; 31.6%), non-ICM (45.6%) and
      explantation of implantable cardioverter defibrillator due to device infection
      (11.4%). We observed sustained VA in 9.6% of the study population and 6.1%
      received an appropriate shock. VA occurred in 16.7% of ICM, 3.8% of non-ICM and
      15.4% of patients with device infection. CONCLUSIONS: Our data demonstrate a very
      high rate of sustained VA in patients at risk for SCD during WCD use. ICM
      patients, including those with recent MI, bore the highest risk.

PMID- 28499629
TI  - Nonobstructive Reproductive Tract Anomalies: A Review of Surgical Management.
AB  - Mullerian anomalies include a spectrum of anatomic variants of the genital tract
      arising from abnormal embryologic development, ranging from incomplete resorption
      of uterine septa to complete vaginal agenesis. Nonobstructive anomalies are often
      recognized later than obstructive anomalies, because women do not present with
      pain. However, nonobstructive anomalies frequently have a negative impact on
      sexual and reproductive health, and careful evaluation and management of these
      disorders is warranted. This review focuses on the surgical management of
      nonobstructive Mullerian anomalies.

PMID- 28499630
TI  - Effect of surface alkali-based treatment of titanium implants on ability to
      promote in vitro mineralization and in vivo bone formation.
AB  - : This study investigated whether a novel alkali-based surface modification
      enhances in vitro mineralization as well as in vivo bone formation around
      titanium (Ti) implants in a femoral condyle model of 36 male Wister rats. All
      implant surfaces were grit-blasted and then received either acid-etching
      treatment, alkali-based treatment, or were left untreated (controls).
      Histological and histomorphometrical analyses were performed on retrieved
      specimens after 4 and 8weeks of healing to assess peri-implant bone formation.
      Results of implants surface characterisation showed notable differences in the
      topography and composition of alkali-treated surfaces, reflecting the formation
      of submicron-structured alkali-titanate layer. In the in vitro test, alkali
      treated Ti surfaces showed the ability to stimulate mineralization upon soaking
      in simulated body fluid (SBF). In vivo histomorphometrical analyses showed
      similar values for bone area (BA%) and bone-to-implant contact (BIC%) for all
      experimental groups after both 4- and 8-week implantation periods. In conclusion,
      the surface topography and composition of the grit-blasted Ti implants was
      significantly modified using alkali-based treatment. With respect to the present
      in vivo model, the biological performance of alkali-treated Ti implants is
      comparable to the commercially available, grit-blasted, acid-etched Ti implants.
      STATEMENT OF SIGNIFICANCE: Since success rate of dental implants might be
      challenged in bone of low density, an optimum implant surface characteristic is
      demanding. In this work, alkali treatment of Ti implants showed significant
      advantage of surface mineralization upon soaking in simulated body fluid. Using
      an in vivo rat model, Ti surfaces with either acid-etching treatment or alkali
      based treatment evoked robust bone formation around Ti implants. Such information
      may be utilized for the advancement of biomaterials research for bone implants in
      future.

PMID- 28499631
TI  - Extrafibrillar collagen demineralization-based chelate-and-rinse technique
      bridges the gap between wet and dry dentin bonding.
AB  - : Limitations associated with wet-bonding led to the recent development of a
      selective demineralization strategy in which dentin was etched with a reduced
      concentration of phosphoric acid to create exclusive extrafibrillar
      demineralization of the collagen matrix. However, the use of acidic conditioners
      removes calcium via diffusion of very small hydronium ions into the
      intrafibrillar collagen water compartments. This defeats the purpose of limiting
      the conditioner to the extrafibrillar space to create a collagen matrix
      containing only intrafibrillar minerals to prevent collapse of the collagen
      matrix. The present work examined the use of polymeric chelators (the sodium salt
      of polyacrylic acid) of different molecular weights to selectively demineralize
      extrafibrillar dentin. These polymeric chelators exhibit different affinities for
      calcium ions (isothermal titration calorimetry), penetrated intrafibrillar dentin
      collagen to different extents based on their molecular sizes (modified size
      exclusion chromatography), and preserve the dynamic mechanical properties of
      mineralized dentin more favorably compared with completely demineralized
      phosphoric acid-etched dentin (nanoscopical dynamic mechanical analysis).
      Scanning and transmission electron microscopy provided evidence for retention of
      intrafibrillar minerals in dentin surfaces conditioned with polymeric chelators.
      Microtensile bond strengths to wet-bonded and dry-bonded dentin conditioned with
      these polymeric chelators showed that the use of sodium salts of polyacrylic acid
      for chelating dentin prior to bonding did not result in significant decline in
      resin-dentin bond strength. Taken together, the findings led to the conclusion
      that a chelate-and-rinse conditioning technique based on extrafibrillar collagen
      demineralization bridges the gap between wet and dry dentin bonding. STATEMENT OF
      SIGNIFICANCE: The chelate-and-rinse dental adhesive bonding concept
      differentiates from previous research in that it is based on the size-exclusion
      characteristics of fibrillar collagen; molecules larger than 40kDa are prevented
      from accessing the intrafibrillar water compartments of the collagen fibrils.
      Using this chelate-and-rinse extrafibrillar calcium chelation concept, collagen
      fibrils with retained intrafibrillar minerals will not collapse upon air-drying.
      This enables adhesive infiltration into the mineral-depleted extrafibrillar
      spaces without relying on wet-bonding. By bridging the gap between wet and dry
      dentine bonding, the chelate-and-rinse concept introduces additional insight to
      the field by preventing exposure of endogenous proteases via preservation of the
      intrafibrillar minerals within a collagen matrix. If successfully validated, this
      should help prevent degradation of resin-dentine bonds by collagenolytic enzymes.

PMID- 28499632
TI  - A comprehensive study of layer-specific morphological changes in the
      microstructure of carotid arteries under uniaxial load.
AB  - : The load bearing properties of large blood vessels are principally conferred by
      collagen and elastin networks and their microstructural organization plays an
      important role in the outcomes of various arterial pathologies. In particular,
      these fibrous networks are able to rearrange and reorient spatially during
      mechanical deformations. In this study, we investigate for the first time whether
      these well-known morphological rearrangements are the same across the whole
      thickness of blood vessels, and subsequently if the underlying mechanisms that
      govern these rearrangements can be predicted using affine kinematics. To this
      aim, we submitted rabbit carotid samples to uniaxial load in three distinct
      deformation directions, while recording live images of the 3D microstructure
      using multiphoton microscopy. Our results show that the observed realignment of
      collagen and elastin in the media layer, along with elastin of the adventitia
      layer, remained limited to small angles that can be predicted by affine
      kinematics. We show also that collagen bundles of fibers in the adventitia layer
      behaved in significantly different fashion. They showed a remarkable capacity to
      realign in the direction of the load, whatever the loading direction. Measured
      reorientation angles of the fibers were significantly higher than affine
      predictions. This remarkable property of collagen bundles in the adventitia was
      never observed before, it shows that the medium surrounding collagen in the
      adventitia undergoes complex deformations challenging traditional hyperelastic
      models based on mixture theories. STATEMENT OF SIGNIFICANCE: The biomechanical
      properties of arteries are conferred by the rearrangement under load of the
      collagen and elastin fibers making up the arterial microstructure. Their
      kinematics under deformation is not yet characterized for all fiber networks. In
      this respect we have submitted samples of arterial tissue to uniaxial tension,
      simultaneously to confocal imaging of their microstructure. Our method allowed
      identifying for the first time the remarkable ability of adventitial collagen
      fibers to reorient in the direction of the load, achieving reorientation
      rotations that exceeded those predicted by affine kinematics, while all other
      networks followed the affine kinematics. Our results highlight new properties of
      the microstructure, which might play a role in the outcomes of vascular
      pathologies like aneurysms.

PMID- 28499633
TI  - Controllable release of nitric oxide and doxorubicin from engineered nanospheres
      for synergistic tumor therapy.
AB  - : NaYF4:Yb,Er upconversion nanoparticles (UCNPs) capped with long-chain
      carboxylic acid were synthesized and then conjugated with chitosan (CS) in the
      aid of N-hydroxysuccinimide. The resultant nanocompound was integrated with
      doxorubicin (DOX) and Roussin's black salt (RBS), a photosensitive nitric oxide
      (NO) donor to produce stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres as
      nanocarriers for controllable drug delivery. On the one hand, the encapsulated
      UCNPs can efficiently absorb NIR photons and convert them into visible photons to
      trigger NO release. On the other hand, the entrapped DOX can be released at
      lowered pH from the swollen nanospheres caused by stretched oleoyl-CS chains
      under acidic conditions. The UCNPs(DOX)@CS-RBS nanospheres exhibit great
      therapeutic efficacy, which is attributable to the combination of NO and DOX
      releases based on NO dose-dependent mechanisms. This study highlights the
      controllable release of NO and DOX from the same nanocarriers and the synergistic
      therapeutic effect on tumors, which could give new insights into improving cancer
      nanotherapeutics. STATEMENT OF SIGNIFICANCE: In this paper, core-shell structured
      UCNPs(DOX)@CS-RBS nanospheres have been designed and synthesized via a step-by
      step procedure. The stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres act as
      nanocarriers for controllable drug delivery towards cancer therapy. The
      encapsulated UCNPs can efficiently absorb NIR photons and convert them into
      visible light to trigger NO release. Meanwhile, the entrapped DOX can be released
      from the swollen nanospheres caused by stretched oleoyl-CS chains at lowered pH
      typical of intracellular environment. Synergistic cancer therapy will be achieved
      through the combination of NO and DOX releases based on NO dose-dependent
      mechanisms. This study provides new drug nanocarriers with high antitumor
      efficacy for synergistic cancer therapy.

PMID- 28499634
TI  - A 'degradable' poly(vinyl alcohol) iron oxide nanoparticle hydrogel.
AB  - : Polymeric materials that contain magnetic nanoparticles are extremely useful in
      many applications including as multifunctional drug carriers, imaging contrast
      agents, or scaffold material. There is a need for biomaterials with appropriate
      chemical, mechanical, and magnetic properties that also have the ability to
      degrade or dissolve over time so they can be eliminated from the body following
      use. In this work, we explore the use of iron oxide nanoparticle (IONP) formation
      in poly(vinyl alcohol) (PVA) as a crosslinking method in conjunction with
      physical crosslinking achieved using low temperature thermal cycling (LTTC). PVA
      IONP hydrogels were fabricated and characterized. IONPs contribute to the
      crosslinking of the PVA-IONP material, and their subsequent removal reduces
      crosslinking, and therefore stability, of the material, allowing dissolution to
      occur. Dissolution studies were performed on PVA-IONP hydrogels and dissolution
      was compared for films in solutions of varying pH, in the presence of iron
      chelating agents, and in simulated physiological and tumor conditions in cell
      culture media. Iron release, mass loss, and mechanical testing data was
      collected. This work demonstrates the ability of this biomaterial to 'degrade'
      over time, which may be very advantageous for applications such as drug delivery.
      This importance of this work extends to other areas such as the use of stimuli
      responsive hydrogels. STATEMENT OF SIGNIFICANCE: This manuscript explores the
      stability of an iron oxide nanoparticle (IONP)-containing, physically crosslinked
      poly(vinyl alcohol) (PVA) hydrogel. The PVA-IONP hydrogel's stability is imparted
      through crosslinks created through a low temperature thermal cycling process and
      through the IONPs. Subsequent IONP removal reduces crosslinks so material
      dissolution can occur, resulting in a 'degradable' and multifunctional
      biomaterial. PVA-IONP films were fabricated, characterized and evaluated in terms
      of dissolution in solutions of varying pH and in the presence of chelating
      agents. Iron release, mass loss, and mechanical testing data demonstrate the
      ability of the PVA-IONP biomaterial to 'degrade' over time. This degradability
      has not yet been demonstrated for crosslinked PVA hydrogels. These results are
      relevant to the development of degradable multifunctional drug carriers, image
      contrast agents, or magnetic scaffold materials.

PMID- 28499635
TI  - Adenosine A2A receptors are up-regulated and control the activation of human
      alveolar macrophages.
AB  - Chronic inflammatory lung diseases remain a health concern and new anti
      inflammatory treatments are needed. Targeting adenosine A2A receptors (A2AR)
      affords robust anti-inflammatory effects in animal models, but the translation of
      this promising strategy to humans has been challenging, possibly due to
      interspecies differences in receptor distribution and effects. Thus, we now
      assessed the efficiency of a selective A2AR agonist to control the activation of
      fresh human alveolar inflammatory cells. We collected bronchoalveolar lavage
      fluid from patients with interstitial lung disease and loaded alveolar cells with
      the intracellular free calcium probe FURA-2/AM. Calcium transients were then
      recorded in response to superfusion with a proinflammatory peptide (N
      formylmethionyl-leucyl-phenylalanine - FMLP), in the absence or presence of the
      selective A2AR agonist CGS21680. In a second experiment, cells were continuously
      exposed to FMLP and A2AR density was assessed by immunocytochemistry. Sixteen
      patients were included, nine for analysis of calcium transients, and seven for
      immunocytochemistry. When alveolar macrophages were exposed to 100 nM FMLP for
      120 s, a peak elevation of intracellular free calcium levels (97.0% over
      baseline) was recorded; CGS21680 (100 and 300 mM) significantly reduced this peak
      to 89.5% and 81.5%, respectively. The immunofluorescence analysis revealed a time
      dependent increase of A2AR density in alveolar macrophage upon exposure to 1 MUM
      FMLP, up to 148% of control at 6 h. These results show that pro-inflammatory
      stimuli up-regulate A2AR and their activation dampens the impact of pro
      inflammatory stimuli. This supports that targeting A2AR is a promising therapy
      for human lung inflammatory diseases, especially for diseases with a strong
      inflammatory component.

PMID- 28499636
TI  - [Is there a role for therapeutic education to prevent acute COPD exacerbations?]

PMID- 28499637
TI  - [Preventive measures after acute COPD exacerbations].

PMID- 28499638
TI  - [Appropriate investigations during an acute COPD exacerbation requiring
      hospitalization].

PMID- 28499639
TI  - [Appropriate investigations during acute COPD exacerbations in community-based
      practice].

PMID- 28499640
TI  - [What is the place for biomarkers during acute COPD exacerbations?]

PMID- 28499641
TI  - Outcomes of research biopsies in clinical trials of EGFR mutation-positive non
      small cell lung cancer patients pretreated with EGFR-tyrosine kinase inhibitors.
AB  - BACKGROUND/PURPOSE: Research biopsies (RBs) are crucial for developing novel
      molecular targeted agents. However, the safety and diagnostic yields of RBs have
      not been investigated in EGFR mutation-positive non-small cell lung cancer
      (NSCLC) patients pretreated with epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (TKIs). METHODS: We searched the medical records of NSCLC
      patients who participated in lung cancer clinical trials and underwent mandatory
      RBs between 2012 and 2014 at our institution. Only patients with EGFR mutation
      positive NSCLC pretreated with at least 1 EGFR-TKI were enrolled. RESULTS: Of 140
      enrolled patients, 73 (52.1%) and 59 (42.1%) had exon 19 deletions and exon 21
      L858R mutation, respectively. Before RBs, 108 (77.1%), 83 (59.3%), and 36 (25.7%)
      patients had been treated with gefitinib, erlotinib, and afatinib, respectively.
      Computed tomography-guided percutaneous core needle biopsy was the most
      frequently used modality among 181 RBs performed (50.8%), followed by
      ultrasonography-guided (32.0%) and endoscopic RBs (16.0%). The most common RB
      sites were the lung (69.6%), pleura (8.8%), and liver (6.1%). Pathologic
      examinations revealed malignant cells in most RB specimens (72.9%). Complications
      due to RBs included pneumothorax (11.6%), bleeding (6.1%), and infection (1.1%).
      Only 1 patient required chest tube placement for pneumothorax, and 2 patients
      underwent endotracheal intubation because of bleeding. CONCLUSION: RBs in this
      patient population were generally safe. Pneumothorax was the most frequent
      complication; bleeding, while infrequent, increased the risk of severe events.
      The diagnostic yields and complications of any particular modality should
      therefore be discussed with prospective clinical trial participants.

PMID- 28499642
TI  - Efficiency of four currently used decontamination conditionings in Romania
      against Aspergillus and Candida strains.
AB  - INTRODUCTION: Efficacy of four commercial biocidal products (noted A to D), using
      manufacturers' recommendations, and a contact time of 30minutes, were evaluated
      in the purpose of standard SR EN1657: 2006 adapted. METHODS: Were used four
      strains, two as reference: Aspergillus brasiliensis (niger) (ATCC 16404) and
      Candida albicans (ATCC 10231), and two isolates: Aspergillus flavus and
      respectively Aspergillus fumigatus. The inoculum plates containing Malt Extract
      Agar (MEA) were incubated 48h for C. albicans and 72hours for Aspergillus spp.
      The standard SR EN1657: 2006 adapted was conducted in two phases: the test
      cultures preparation and the method validation. Method validation included: the
      control of experimental conditions and of neutralizant solution, and the method
      verification. RESULTS: Results revealed that three from the four tested products
      (A, B and D) had exerted biocidal effect on the studied strains at the
      recommended concentrations, the registered CFU values being reduced by more than
      4 log10, conversely in the case of the product (C), applied against A. fumigatus
      at the recommended concentration of 2%, the biocidal effect was not detected,
      fact confirmed also by the CFU's value (3.59 log10). The biocide retested at a
      greater concentration (of 5%), showed a biocidal effect against A. fumigatus
      after 30minutes, the CFU value being reduced, by more than 5.29 log10, evidencing
      the resistance emergence of A. fumigatus under the repeated pressure of biocides.
      CONCLUSION: It is re-confirming that merely the "chemical" defense measures to
      defuse the fungi's strategies become unproductive.

PMID- 28499643
TI  - Pharmacokinetic profile of bilberry anthocyanins in rats and the role of glucose
      transporters: LC-MS/MS and computational studies.
AB  - The aim of the present investigation was to better understand the pharmacokinetic
      profile of bilberry (Vaccinium Myrtillus) anthocyanins and the role of glucose
      transporters (sGLT1 and GLUT2) on their absorption. In particular, the absorption
      of 15 different anthocyanins contained in a standardized bilberry extract
      (Mirtoselect(r)) was measured in rats by a validated LC-ESI-MS/MS approach. The
      plasma concentration peak (Cmax) of 11.1ng/mL was reached after 30min and fasting
      condition significantly increased the bioavailability of anthocyanins by more
      than 7 fold in respect to fed rats. Glucose co-administration did not interfere
      with the overall anthocyanin uptake. Bioavailability of each anthocyanin was then
      estimated by comparing the relative content in plasma vs extract. The 15
      anthocyanins behaved differently in term of bioavailability and both the aglycone
      and the sugar moiety were found to affect the absorption. For instance,
      arabinoside moiety was detrimental while cyanidin enhanced bioavailability.
      Computational studies permitted to rationalize such results, highlighting the
      role of glucose transporters (sGLT1 and GLUT2) in anthocyanins absorption. In
      particular a significant correlation was found for the 15 anthocyanins between
      sGLT1 and GLUT2 recognition and absorption.

PMID- 28499644
TI  - Simple and rapid LC-MS method for the determination of circulating albumin
      microheterogeneity in veal calves exposed to heat stress.
AB  - Heat stress has a major impact on veal calves welfare and productivity. Prolonged
      exposure to warm temperature is associated with several alterations of
      physiologic processes and increased systemic inflammation and oxidative stress.
      Bovine serum albumin (BSA) is the most abundant plasma protein and, besides the
      regulation of osmotic pressure, carries several additional functions, including
      antioxidant, immunomodulatory, binding and transport activities. Such non-oncotic
      properties are closely related to structural integrity of the circulating
      molecule and may be compromised in stressful microenvironments as it occurs in
      heat stressed animals. Thus, in the present study we developed and validated an
      LC-MS analytical technique for the characterization of circulating BSA
      microheterogeneity in veal calves exposed to heat stress. The method was
      specifically tailored to the structural characteristics of the BSA molecule as
      well as to the complexity of the biological samples, allowing the identification
      of several BSA isoforms, each characterized by a specific structural defect. The
      mass spectrometry based approach enabled the identification of BSA isoforms with
      reversible and irreversible oxidation and/or glycation and the native BSA, the
      only isoform endowed with structural and functional integrity. We found that, in
      veal calves, heat stress is associated to a significant reduction of the native
      BSA and to a significant increment of the reversibly and irreversibly oxidized
      BSA. Then, by monitoring the BSA microheterogeneity over a period of moderate
      heat stress, we found that the native BSA as well as the glycated BSA increased
      significantly during the recovery period. Based on our results the analysis of
      the BSA microheterogeneity could represent a novel biomarker for the assessment
      of animal welfare during environmental stressful conditions.

PMID- 28499645
TI  - Healing: Moving Toward Health and Wholeness.

PMID- 28499646
TI  - Dancing partners at the ball: Rational selection of next generation anti-CD20
      antibodies for combination therapy of chronic lymphocytic leukemia in the novel
      agents era.
AB  - The anti-CD20 antibodies represent a major advancement in the therapeutic options
      available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab
      and obinutuzumab to various chemotherapy regimens has led to considerable
      improvements in both response and survival. Ocaratuzumab, veltuzumab and
      ublituximab are currently being explored within the trial setting. We review the
      current status of these antibodies, and discuss how their mechanisms of action
      may impact on the choice of combinations with novel small molecule agents.

PMID- 28499647
TI  - Commentary to "Assessment of Competence in EVAR Procedures - A Novel Rating Scale
      Developed by the Delphi Technique".

PMID- 28499648
TI  - Ovarian cancer spheroid shrinkage following continuous exposure to cisplatin is a
      function of spheroid diameter.
AB  - OBJECTIVE: Most ovarian cancer patients present with advanced-stage disease,
      disseminated in the peritoneal cavity. Standard treatment involves surgical
      resection of all visible tumor, followed by delivery of systemic therapy.
      Patients with advanced-stage disease may be candidates for intraperitoneal (IP)
      chemotherapy following surgical debulking. Recent clinical trials have created
      controversy regarding the benefits of this approach. Previous clinical trials
      report that patients with microscopic residual disease respond best to IP
      therapy. The goal of this study was to determine the relationship between tumor
      size and the efficacy of continuous chemotherapy. METHODS: Small and large
      ovarian cancer spheroids (derived from UCI101 and A2780 cell lines) were exposed
      to short-term high (modeling an IP injection, "IP") or prolonged, low cisplatin
      concentrations (modeling an implanted device, "device"), which have been
      previously shown to be less toxic. Spheroid diameter was measured at various time
      points via image analysis and used to quantify tumor shrinkage over the course of
      treatment. RESULTS: We show that "IP" doses more effectively shrink large
      spheroids when the same cumulative dose is administered with both treatments, but
      that both regimens similarly treat small spheroids. We also demonstrate that
      higher cumulative "device" doses are most effective at shrinking large spheroids.
      CONCLUSIONS: These results support the hypothesis that intratumoral drug
      distribution following IP treatment is diffusion-controlled. An implanted device
      that continuously delivers low doses of IP chemotherapy would, therefore, be
      maximally effective against microscopic tumors.

PMID- 28499649
TI  - A SEER-Medicare analysis of the impact of metformin on overall survival in
      ovarian cancer.
AB  - OBJECTIVE: Determine whether metformin use is associated with improved survival
      in patients with ovarian, fallopian tube or primary peritoneal cancer. METHODS:
      All patients with a diagnosis of first epithelial ovarian cancer from 2007 to
      2011 in the combined SEER-Medicare database were identified from the SEER
      registry primary site codes. Comorbidities, procedures and cancer treatment ICD-9
      and HCPCS codes were used to search the Medicare claims files. Medication use was
      determined with National Drug Codes using the Medicare Part D event files. The
      primary outcome, overall survival, was assessed between metformin users and non
      users using a Cox Proportional Hazards survival model. To control for
      confounding, metformin users were matched to non-metformin users using propensity
      scores. Effect of dosage on survival was assessed using discrete time survival
      analysis with pooled logistic regression (PLR). RESULTS: There were 2291 cases
      that met our inclusion criteria. Of these, 180 (7.9%) had been on metformin. The
      median age was 73years, with the majority of the population being White (83.5%)
      and treated with primary surgery (74.1%). Metformin use was not associated with
      overall survival in the entire cohort (HR 0.96, 95% CI 0.75-1.23) or in the
      matched sample cohort (HR 0.88, 95% CI 0.66-1.17). However, exploratory
      regression with time-varying coefficients suggests a protective metformin effect
      for women alive after 30months follow-up (HR=0.37, 95% 0.16-0.87). CONCLUSION: No
      statistically significant association was observed between metformin use and
      overall survival in a matched cohort of 360 ovarian cancer patients. However,
      exploratory modeling suggests metformin use may be protective in a certain
      subgroup of patients.

PMID- 28499651
TI  - Bioprosthetic Aortic Valve Durability: A Meta-Regression of Published Studies.
AB  - To compare structural valve deterioration (SVD) among bioprosthetic aortic valve
      types, a PubMed search found 54 papers containing SVD-free curves extending to at
      least 10 years. The curves were digitized and fit to Weibull distributions, and
      the mean times to valve failure (MTTF) were calculated. Twelve valve models were
      collapsed into four valve types: Medtronic (Medtronic, Minneapolis, MN) and
      Edwards (Edwards Lifesciences, Irvine, CA) porcine; and Sorin (Sorin Group [now
      LivaNova], London, United Kingdom) and Edwards pericardial. Meta-regression found
      MTTF was associated with the patient's age, publication year, SVD definition, and
      valve type. Sorin pericardial valves had significantly lower risk-adjusted MTTF
      (higher SVD risk), and there were no significant differences in MTTF among the
      other three valve types.

PMID- 28499650
TI  - The Mesenchymal State Predicts Poor Disease-Free Survival in Resectable Non-Small
      Cell Lung Cancer.
AB  - BACKGROUND: The epithelial-mesenchymal transition (EMT) is thought to contribute
      to the overall invasiveness of malignant cells. Expression of cluster of
      differentiation (CD) 44 and CD90 mark the mesenchymal state in multiple
      epithelial malignancies. Their role in lung cancer remains unclear, however. This
      study evaluated the prognostic significance of CD44 and CD90 coexpression in
      patients with resectable primary non-small cell lung cancer (NSCLC). METHODS:
      This was a nonconcurrent cohort study of patients with resectable NSCLC,
      stratified by the degree of expression of CD44/CD90 double-positive cells in
      their primary tumor. Flow cytometry was used for immunophenotyping of freshly
      isolated disaggregated tumor. We analyzed the relationship between expression of
      CD44/CD90 and relapse-free survival. RESULTS: We evaluated 37 patients (18 men;
      median age, 70 years) with NSCLC. For this group, the geometric mean proportion
      of cells coexpressing CD44/CD90 was 0.52%. Expression of CD44/CD90 was
      significantly elevated (24.4%, geometric mean) in 6 patients. The median relapse
      free survival for patients with high CD44/CD90 coexpression was 7.7 months (95%
      confidence interval, 4.2 to 11.7) compared with 40 months (95% confidence
      interval, 18.2 to 77.8) for the group with low CD44/CD90 coexpression (p =
      0.00006 by Mantel log-rank test). The assessment of risk based upon CD44/CD90
      expression status was not correlated with pathologic staging (p = 0.073 by chi2).
      CONCLUSIONS: High expression of CD44 and CD90 was associated with significantly
      reduced relapse-free survival in NSCLC patients. These results suggest that CD44
      and CD90 may be important markers of tumor progression in NSCLC.

PMID- 28499652
TI  - Lack of Furosemide Responsiveness Predicts Acute Kidney Injury in Infants After
      Cardiac Surgery.
AB  - BACKGROUND: This was a retrospective study to determine whether lack of
      furosemide responsiveness (LFR) predicts acute kidney injury (AKI) after
      cardiopulmonary bypass surgery in infants. METHODS: Infants (less than 1 year of
      age) undergoing cardiopulmonary bypass surgery, receiving routine postoperative
      furosemide (0.8 to 1.2 mg/kg per dose between 8 and 24 hours after surgery) were
      included. Urine output was measured 2 and 6 hours after furosemide dose. Lack of
      furosemide responsiveness was defined a priori as urine output less than 1 mL .
      kg-1 . h-1 after furosemide. Serum creatinine was corrected for fluid balance.
      Acute kidney injury was determined using changes in uncorrected and corrected
      serum creatinine. The predictive utility of LFR was assessed using receiver
      operating characteristics curve analysis. RESULTS: We analyzed 568 infants who
      underwent cardiopulmonary bypass. Eighty-one (14.3%) had AKI using uncorrected
      serum creatinine; AKI occurred in 41 (7.2%) after correcting for fluid overload.
      Patients with AKI had a lower response to furosemide (median urine output 2
      hours: 1.2 versus 3.4 mL . kg-1 . h-1, p = 0.01; median urine output 6 hours: 1.3
      versus 2.9 mL . kg-1 . h-1, p = 0.01). After creatinine correction, LFR predicts
      AKI development (area under receiver-operating characteristics curve of 0.74 at 2
      hours and 0.77 at 6 hours). After adjusting for surgical complexity using The
      Society of Thoracic Surgeons/European Association for Cardiothoracic Surgery
      mortality categories, the area under the receiver-operating characteristics curve
      was 0.74 at 2 hours and 0.81 at 6 hours. Patients with urine output greater than
      1 mL . kg-1 . h-1 were unlikely to have AKI (negative predictive value, 97%).
      CONCLUSIONS: After correcting serum creatinine for fluid balance and adjusting
      for surgical complexity, LFR performs fairly at 2 hours, whereas at 6 hours, LFR
      is a good AKI predictor. Prospective studies are needed to validate whether
      diuretic responsiveness predicts AKI.

PMID- 28499653
TI  - Customized Hinged Covered Metallic Stents for the Treatment of Benign Main
      Bronchial Stenosis.
AB  - BACKGROUND: To address the limitations of silicone stents, we designed a hinged
      self-expandable covered metallic stent. The aim of this study was to evaluate the
      safety and efficacy of the customized stents in clinical applications. METHODS:
      This was a retrospective analysis. Under conscious sedation and local anesthesia,
      the stents were implanted or removed by interventional radiologists, with
      fluoroscopic guidance. RESULTS: Of 24 patients with benign main bronchial
      stenosis, stents were successfully placed in 21 (87.5%). The low-pressure balloon
      before dilation failed in 1 case (4.17%) of left main bronchial cicatricial
      stenosis. In 2 other cases (8.33%), stent placement was abandoned. Stents were
      successfully removed between 29 and 103 days after the procedure. After stent
      removal, the follow-up lasted for at least 12 months. Restenosis occurred only in
      1 case (4.55%) owing to bronchial collapse 3 days after stent removal. Dyspnea
      occurred in another case (4.55%) at 2 months after retrieval; recurrence was
      confirmed using bronchoscopy, leading to a left pneumonectomy. CONCLUSIONS: The
      described procedure is safe and easy to be performed and avoids the use of
      intubation, bronchoscopy, and general anesthesia.

PMID- 28499654
TI  - Hybrid Extracorporeal Membrane Oxygenation Using Avalon Elite Double Lumen
      Cannula Ensures Adequate Heart/Brain Oxygen Supply.
AB  - BACKGROUND: Differential hypoxia exists in peripheral venoarterial (VA)
      extracorporeal membrane oxygenation (ECMO) patients with compromised lungs,
      causing hypoxic damage to heart or brain. We proposed an Avalon Elite (Maquet,
      Rastatt, Germany) double lumen cannula-based hybrid ECMO to add a venovenous (VV)
      blood flow into the pulmonary circulation onto the existing VA ECMO circuit to
      increase oxygen saturation in the left ventricle and ascending aorta, mitigating
      heart/brain hypoxia. METHODS: This hybrid ECMO circuit consists of two cannulas
      (27F Avalon Elite double lumen cannula from the inferior vena cava to the
      superior vena cava to right atrium to inferior vena cava; 17F infusion cannula in
      femoral artery), a blood pump, and a gas exchanger. This hybrid ECMO circuit was
      tested in 7 adult sheep with simulated lung failure. Total ECMO blood flow (2.8
      to 3.3 L/min) was split between VV and VA blood flow. The VV blood flow was
      adjusted from 0% to 50% of total ECMO flow by approximately 10% increments.
      RESULTS: In VA ECMO, simulated respiratory failure resulted in differential
      hypoxia (low oxygen level in left ventricle and high oxygen level in abdominal
      aorta). In hybrid ECMO, adding VV blood flow (10% to 50% of total ECMO flow) to
      the VA ECMO circuit progressively increased left ventricle blood oxygen
      saturation from 70% +/- 8% at zero VV blood flow (pure VA ECMO) to 82% +/- 6% at
      300 mL/min VV blood flow, and 96% +/- 6% at 1,700 mL/min VV blood flow.
      CONCLUSIONS: The Avalon Elite double-lumen cannula-based hybrid ECMO circuit is a
      simple circuit that provides efficient performance and flexible VA/VV blood
      distribution. In this hybrid ECMO circuit, incremental VV blood flow (10% to 50%)
      progressively increased left ventricular blood oxygen level, ensuring adequate
      heart and brain oxygen supply.

PMID- 28499655
TI  - Validating the Thoracic Revised Cardiac Risk Index Following Lung Resection.
AB  - BACKGROUND: The Thoracic Revised Cardiac Index (ThRCRI) is a tool that
      differentiates patients who may proceed to lung resection (classes A or B) from
      those who should receive additional cardiac evaluation (classes C or D). This
      study aims to describe the ability of the ThRCRI to stratify patients based on
      major cardiac complication rates using a large multi-institutional dataset.
      METHODS: Patients undergoing lobectomy or pneumonectomy were identified in the
      American College of Surgeons National Surgical Quality Improvement Program
      dataset from 2005 to 2012. Patients were grouped into 4 risk classes based on a
      summary score of preoperative risk factors: ischemic heart disease,
      cerebrovascular disease, renal comorbidity, and pneumonectomy. The primary
      outcome was the incidence of perioperative major cardiac complication in each of
      the 4 risk classes. RESULTS: Of the 4,625 patients identified, the majority
      underwent surgery for malignant disease (78%) and had an open procedure (70%).
      Among ThRCRI risk factors, 9% of patients had ischemic heart disease, 7% had
      cerebrovascular disease, 2% had renal comorbidity, and 6% underwent
      pneumonectomy. Incidence of cardiac complication in all patients was 2%.
      Incidence of cardiac complication within risk classes A, B, C, and D were 1%, 3%,
      9%, and 4%, respectively (p < 0.01). CONCLUSIONS: Using a large multi
      institutional dataset, the ThRCRI can differentiate patients at higher risk for
      cardiac complication following lung resection (classes C and D) and can be a
      useful preoperative instrument. The ThRCRI may allow for identifying patients who
      would benefit from additional cardiac evaluation.

PMID- 28499656
TI  - Outcome of a Step-Up Treatment Strategy for Chyle Leakage After Esophagectomy.
AB  - BACKGROUND: Thoracic chyle leakage is a major complication of esophagectomy. In
      this study our treatment strategy for chyle leakage was evaluated and its risk
      factors were identified. METHODS: According to the Esophagectomy Complications
      Consensus Group recommendations, chyle leakage was classified as follows: I,
      enteric dietary modifications; II, total parenteral nutrition (TPN); and III,
      interventional or surgical therapy. It was graded as A, less than 1,000 mL per
      day; or B, more than 1,000 mL per day. In our protocol, chyle leakage less than
      500 mL per day was treated with a low-fat diet; more than 1,000 mL per day, with
      TPN, and 500 to 1,000 mL per day, with a low-fat diet or TPN depending on whether
      the chyle leakage was increasing or decreasing at diagnosis and the clinical
      condition. Surgery was reserved for refractory leakages. RESULTS: In total 371
      patients were included. Chyle leakage incidence was 21%, consisting of 51% grade
      A and 49% grade B leakage. Chyle leakage severity was associated with length of
      stay (grade A, median 17 days versus B, 25 days; p = 0.006). Independent risk
      factors were a transthoracic approach (odds ratio 4.8, p = 0.002), neoadjuvant
      chemoradiotherapy (odds ratio 2.6, p = 0.002), and preoperative body mass index
      (exp(B) 0.92, p = 0.031). Treatment consisted of low-fat diet in 53%, TPN in 37%,
      and surgery in 10% of the patients. Low-fat diet and TPN successfully treated 87%
      of chyle leaks. Chyle leakages treated by TPN first were significantly more
      severe compared with those treated first by low-fat diet, and were significantly
      associated with electrolyte deficiencies, increased complication severity, and
      length of stay, but not with 90-day mortality. CONCLUSIONS: A step-up treatment
      strategy, starting with dietary modifications, solved nearly 90% of chyle leaks
      conservatively. A minority of chyle leaks required surgery.

PMID- 28499657
TI  - Electrically Assisted Movement Therapy in Chronic Stroke Patients With Severe
      Upper Limb Paresis: A Pilot, Single-Blind, Randomized Crossover Study.
AB  - OBJECTIVE: To evaluate the effects of electrically assisted movement therapy
      (EAMT) in which patients use functional electrical stimulation, modulated by a
      custom device controlled through the patient's unaffected hand, to produce or
      assist task-specific upper limb movements, which enables them to engage in
      intensive goal-oriented training. DESIGN: Randomized, crossover, assessor
      blinded, 5-week trial with follow-up at 18 weeks. SETTING: Rehabilitation
      university hospital. PARTICIPANTS: Patients with chronic, severe stroke (N=11;
      mean age, 47.9y) more than 6 months poststroke (mean time since event, 46.3mo).
      INTERVENTIONS: Both EAMT and the control intervention (dose-matched, goal
      oriented standard care) consisted of 10 sessions of 90 minutes per day, 5
      sessions per week, for 2 weeks. After the first 10 sessions, group allocation was
      crossed over, and patients received a 1-week therapy break before receiving the
      new treatment. MAIN OUTCOME MEASURES: Fugl-Meyer Motor Assessment for the Upper
      Extremity, Wolf Motor Function Test, spasticity, and 28-item Motor Activity Log.
      RESULTS: Forty-four individuals were recruited, of whom 11 were eligible and
      participated. Five patients received the experimental treatment before standard
      care, and 6 received standard care before the experimental treatment. EAMT
      produced higher improvements in the Fugl-Meyer scale than standard care (P<.05).
      Median improvements were 6.5 Fugl-Meyer points and 1 Fugl-Meyer point after the
      experimental treatment and standard care, respectively. The improvement was also
      significant in subjective reports of quality of movement and amount of use of the
      affected limb during activities of daily living (P<.05). CONCLUSIONS: EAMT
      produces a clinically important impairment reduction in stroke patients with
      chronic, severe upper limb paresis.

PMID- 28499658
TI  - [Radiotherapy volume delineation based on (18F)-fluorodeoxyglucose positron
      emission tomography for locally advanced or inoperable oesophageal cancer].
AB  - PURPOSE: To study the impact on radiotherapy planning of an automatically
      segmented target volume delineation based on (18F)-fluorodeoxy-D-glucose (FDG)
      hybrid positron emission tomography-computed tomography (PET-CT) compared to a
      manually delineation based on computed tomography (CT) in oesophageal carcinoma
      patients. METHODS AND MATERIALS: Fifty-eight patients diagnosed with oesophageal
      cancer between September 2009 and November 2014 were included. The majority had
      squamous cell carcinoma (84.5 %), and advanced stage (37.9 % were stade IIIA) and
      44.8 % had middle oesophageal lesion. Gross tumour volumes were retrospectively
      defined based either manually on CT or automatically on coregistered PET/CT
      images using three different threshold methods: standard-uptake value (SUV) of
      2.5, 40 % of maximum intensity and signal-to-background ratio. Target volumes
      were compared in length, volume and using the index of conformality. Radiotherapy
      plans to the dose of 50Gy and 66Gy using intensity-modulated radiotherapy were
      generated and compared for both data sets. Planification target volume coverage
      and doses delivered to organs at risk (heart, lung and spinal cord) were
      compared. RESULTS: The gross tumour volume based manually on CT was significantly
      longer than that automatically based on signal-to-background ratio (6.4cm versus
      5.3cm; P<0.008). Doses to the lungs (V20, Dmean), heart (V40), and spinal cord
      (Dmax) were significantly lower on plans using the PTVSBR. The PTVSBR coverage
      was statistically better than the PTVCT coverage on both plans. (50Gy: P<0.0004
      and 66Gy: P<0.0006). CONCLUSION: The automatic PET segmentation algorithm based
      on the signal-to-background ratio method for the delineation of oesophageal
      tumours is interesting, and results in better target volume coverage and
      decreased dose to organs at risk. This may allow dose escalation up to 66Gy to
      the gross tumour volume.

PMID- 28499660
TI  - Stereotactic radiation therapy of brain metastases from colorectal cancer: A
      single institution cohort.
AB  - PURPOSE: The brain remains an uncommon site of colorectal cancer metastases. Due
      to the improvement of overall colorectal cancer patient survival, the incidence
      of brain metastases will likely rise. We report the efficacy and safety of
      hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery,
      and its role in colorectal cancer brain metastasis management. METHODS AND
      MATERIAL: Between June 2010 and December 2014, fifteen consecutive patients
      received hypofractionnated stereotactic radiation therapy or stereotactic
      radiosurgery as first local therapy or following surgical removal for colorectal
      cancer brain metastases. The primary endpoint was overall survival. Secondary
      endpoints were brain progression free survival, in field control rates and
      safety. RESULTS: Median follow-up was 41 months (95% confidence interval [CI]:
      [8.9-73.1 months]), median overall survival was 8 months (95% CI [4.7-11.3
      months]), and median brain progression-free survival was 5 months (95% CI [3.9
      6.1 months]). Five in field recurrences were observed, which makes a control rate
      per metastases at 6 and 12 months of 77.8% (95% CI [74.34%-81.26%]), 51.9% (95%
      CI [44.21%-59.59%]) respectively. Over the 19 treatment sequences, five in field
      recurences were observed: 6, 12 and 18 months control rate per treatment sequence
      were 93.3% (95% CI [90.42%-96.18%]), 68.1% (95% CI [62.03%-74.17%]) and 45.4%
      (95% CI [36.14%-54.66%]) respectively. Immediate tolerance was good with no
      toxicity grade III or more. Long-term toxicity included two radionecrosis among
      which, one was symptomatic. DISCUSSION: The results of this retrospective
      analysis suggest that hypofractionnated stereotactic radiation therapy and
      stereotactic radiosurgery are effective and safe treatment modalities for single
      and multiple small brain metastases from colorectal cancer. However, results need
      to be confirmed by multicenter, collected data.

PMID- 28499659
TI  - [Spinal stereotactic body radiotherapy: French assessment in 2016].
AB  - PURPOSE: Stereotactic body radiotherapy to vertebral column remains uncommon
      practice and only relevant in selected group of patients. The main objective of
      the study was to describe the current state of medical practices of stereotactic
      body radiotherapy to vertebral column in France in 2016 and to assess the
      diversity of practices to identify areas for improvement and establish a common
      database set for this technique. MATERIALS AND METHODS: A questionnaire was
      written with contribution of a medical physicist, a radiation oncologist, an
      information technologist and a radiotherapy resident. The questionnaire was
      distributed online to a radiation oncologists and a medical physicists partner of
      selected French radiotherapy specialized centres that provide stereotactic body
      radiotherapy to vertebral metastasis from April to June 2016. The questionnaire
      surveyed the following topics: patients' selection, simulation, targeted volume
      and organs at risk delineation, prescription, dosimetric implementation and image
      guidance. RESULTS: A total of 31 centres were surveyed. Seventy eight per cent of
      centres (n=21) completed the questionnaire. The "ideal" patient for spine
      stereotactic radiotherapy according to these institutions has a good performance
      status, a long life expectancy, controlled primary tumour with oligometastatic
      spread. The most prescribed protocol was 30Gy in three fractions. For clinical
      target volume delineation, about two thirds of centres used the International
      Spine Radiosurgery Consortium (ISRC) recommendations (Noel G et al.,2006).
      CONCLUSION: This study identified some consistency of practices in some aspects
      despite the lack of consensus guidelines. Nevertheless, further studies are
      needed to establish consensus of planning and treatment.

PMID- 28499661
TI  - Second malignancies after permanent implant prostate cancer brachytherapy: A
      single-institution study of 675 patients treated between 1999 and 2003.
AB  - PURPOSE: To analyse the rate of secondary malignancies observed in a series of
      675 prostate cancer patients who underwent a permanent implant brachytherapy
      between 1999 and 2003, and to compare the incidence with the expected rate in a
      matched general French population. MATERIAL AND METHODS: The cohort included low
      risk patients and a selection of "favourable-intermediate" risk patients. All
      patients were homogeneously treated using an intraoperative dynamic planning
      prostate brachytherapy technique, with loose 125-iodine seeds and a prescription
      dose of 145Gy. The mean follow-up was 132 months. RESULTS: The 10-year overall
      survival for the entire cohort was 92% (95% confidence interval [CI]: 90-94). The
      10-year relapse-free survival rate was 82% (95% CI: 79-85). Overall, 61 second
      cancers were registered. When comparing with a matched general French population,
      the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46
      1.93). For colorectal cancer, the SIR was 0.45 (95% CI: 0.19-0.89). For lung
      cancer, the SIR was 0.38 (95% CI: 0.17-0.76). The SIR for all cancers was 0.61
      (95% CI: 0.47-0.79). When excluding secondary colorectal and lung cancers (both
      with low SIRs in this series), the SIR for all cancers was 1.06 (95% CI: 0.77
      1.29). CONCLUSION: With a mean follow-up of more than 11 years, this series does
      not detect any excess risk of second cancers associated with permanent implant
      prostate brachytherapy. However, due to power limitation, a small increase in the
      risk of secondary malignancies cannot be totally ruled out.

PMID- 28499662
TI  - [Acute toxicity of breast cancer irradiation with modulated intensity by
      tomotherapy(r)].
AB  - PURPOSE: Helical radiation intensity modulated by tomotherapy improves dose
      distribution to complex and large volumes. The aim of the study was to assess
      acute toxicity of this technique during breast cancer irradiation after
      conserving surgery or mastectomy. PATIENTS AND METHODS: Cutaneous toxicities,
      lung and oesophageal side effects, and breast lymphedema were retrospectively
      collected according to the Common Terminology Criteria for Adverse Events Version
      4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy
      between May 2010 and December 2014. After conservative surgery, the dose
      administered to breast volume and the tumour bed was respectively 52.2Gy and
      63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions.
      Univariate and multivariate analyses were performed to highlight risk factors for
      dermatitis and breast oedema. RESULTS: The rate of dermatitis grade 2 and 3 were
      22.9% and 1.7% respectively. In univariate analysis, factors associated with
      acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI)
      (P<0.0001), the use of chest compression mask (net) (P=0.005) and the
      localization of the irradiation (P <0.0001). In multivariate analysis, BMI
      greater than 25kg/m2 (odds ratio [OR]: 3.61, 95% confidence interval [CI]: [1.93
      6.74], P<0.0001), the use of a chest mask (OR 2.01, 95% CI [1.06-3.79] P=0.0328)
      and irradiation after conservative treatment increase the risk of acute radiation
      dermatitis (mastectomy: OR 0.64, 95% CI [0.04-0.43]; mastectomy with immediate
      reconstruction with prosthesis: OR 0.13 95% CI [0.10-0.38] P=0.0003). The
      incidence of breast oedema grade 2 or above was 19.5%, in univariate analysis,
      there was a correlation with BMI (P=0.003) and smoking (P=0.009). In multivariate
      analysis, smoking and BMI greater than 25kg/m2 increased the risk of breast
      oedema (OR 2.47, respectively [95% CI 1.22-5.01] P=0.012 and OR 2.37 [95% CI 1.22
      4.59] P=0.01). The rate of radiation pneumonitis of grade 2 or above was 1.4%.
      Among the patients, 19.9% had esophagitis grade 1 or 2. CONCLUSION: The helical
      irradiation intensity modulation tomotherapy is a well-tolerated treatment for
      breast cancer that reduces the high radiation doses to organs at risk.

PMID- 28499663
TI  - Htr2c Splice Variants and 5HT2CR-Mediated Appetite.
AB  - Serotonin 2C receptor (5HT2CR) exists as different isoforms as a result of
      alternate splicing. A truncated variant (5HT2CR-trunc) has no canonical receptor
      function and yet shows robust expression levels throughout the brain. Recent work
      has demonstrated the biochemical role of this isoform and how altering levels of
      5HT2CR-trunc leads to changes in behaviour.

PMID- 28499664
TI  - STEMI with fluctuating closing of LAD and Cx: Do not concentrate on the finger.
AB  - Case report of the male with an anterior STEMI to whom a primary PCI is
      performed. The angiogram shows a fluctuating close of the LAD and Cx than when an
      OCT is performed does not clearly see any pathological findings but when the IVUS
      is performed, it is clearly seen as a coronary haematoma at the LM, LAD and Cx.
      Stent at the LM-LAD and proximal Cx are implanted with final good result. After
      exchanging the guiding catheter for a diagnostic catheter to visualize the RCA,
      there is an aortic flap; the coronary haematoma was coming from an ascending
      aortic dissection. The CT confirms the type A aortic dissection and the patient
      is sent to urgent surgery where it seems that the point of intimal disruption is
      close to brachiocephalic trunk; a supracommissural ascending aortic replacement
      is performed. After several complications the patient did well and he is alive.
      Although the patient got the right approach, as we focused on the coronary
      arteries we did not realized there was an aortic dissection until the end of the
      procedure.

PMID- 28499665
TI  - Persistent T-wave inversion predicts myocardial damage after ST-elevation
      myocardial infarction.
AB  - BACKGROUND: Persistent T-wave inversion (PTI) after ST-elevation myocardial
      infarction (STEMI) is associated with worse clinical outcome; however, the
      underlying mechanism between PTI and poor prognosis is incompletely understood.
      We sought to investigate the relationship between PTI and myocardial damage
      assessed by cardiac magnetic resonance (CMR) following STEMI. METHODS: In this
      prospective observational study, we included 142 consecutive revascularized STEMI
      patients. Electrocardiography to determine the presence and amplitude of PTI and
      pathological Q-waves was conducted 4months after infarction. CMR was performed
      within 1week after infarction and at 4months follow-up to evaluate infarct
      characteristics and myocardial function. RESULTS: Patients with PTI (n=103, 73%)
      showed a larger acute (21[11-29] vs. 6[1-13]%; p<0.001) and chronic infarct size
      (IS) (14[8-19] vs. 3[1-8]%; p<0.001) and more frequently microvascular
      obstruction (59 vs. 33%; p=0.02). The association between PTI and chronic IS
      remained significant (odds ratio: 9.02, 95%CI 3.49-23.35; p<0.001) after
      adjustment for pathological Q-wave and other IS estimators (high-sensitivity
      cardiac troponin T and C-reactive protein, N-terminal pro B-type natriuretic
      peptide, culprit vessel, pre-interventional TIMI flow). The value of PTI
      amplitude for the prediction of large chronic IS>11% (AUC: 0.84, 95%CI 0.77-0.90)
      was significantly higher compared to Q-wave amplitude (AUC: 0.72, 95%CI 0.63
      0.80; p=0.009); the combination of PTI with pathological Q-wave (Q-wave/T-wave
      score) led to a net reclassification improvement of 0.43 (95% CI 0.29-0.57;
      p<0.001) as compared to PTI alone. CONCLUSIONS: PTI following STEMI is
      independently and incrementally associated with more extensive myocardial damage
      as visualized by CMR. An electrocardiographic score combining PTI with
      pathological Q-wave allows for a highly accurate IS estimation post-STEMI.

PMID- 28499666
TI  - Long-term survival after off-pump versus on-pump coronary artery bypass graft
      surgery. Does completeness of revascularization play a role?
AB  - BACKGROUND: We sought to compare the incidence of incomplete revascularization
      (IR) and long-term survival (up to 20years) after off-pump (OPCAB) versus on-pump
      (ONCAB) coronary artery bypass in a high OPCAB volume centre where OPCAB was
      introduced in 1996 and has become the preferred strategy over the years. METHODS
      AND RESULTS: From 1996 to 2015 a total of 7,427 OPCAB and 7128 ONCAB procedures
      were performed at Bristol Heart Institute, United Kingdom. We obtained 5423
      propensity matched pairs for final comparison. Mixed effect Cox model accounting
      for clustering due to different surgeon was used to investigate the treatment
      effect on mortality. RESULTS: OPCAB was associated with higher rate of incomplete
      revascularization 13.3% versus 6.7%; P<0.0001). Mean follow-up time was 7.8+/
      4.6year [max 17.3]. At 12years OPCAB was associated with a marginal but
      significant +3% increase in overall mortality (67.4%[95%CI 65.8-69.1] vs
      64.4%[95%CI 62.7-66.2]; stratified log-rank P=0.03). When compared to ONCAB with
      complete revascularization, OPCAB with IR (HR 1.74;95%CI 1.53-1.99; P<0.001) and
      ONCAB with IR (HR 1.29; 95%CI 1.06-1.57; P=0.01) but not OPCAB with complete
      revascularization (HR 1.02;95%CI 0.94-1.11; P=0.63) were associated with
      increased risk of late mortality. CONCLUSION: Despite completeness of
      revascularization was achieved in the majority of OPCAB cases, OPCAB remained
      associated with a significantly higher rate of incomplete revascularization. This
      translated into a marginal but significant reduction in late survival rates after
      OPCAB when compared to ONCAB.

PMID- 28499667
TI  - Insight into the incidence of acute aortic dissection in the German region of
      Berlin and Brandenburg.
AB  - BACKGROUND: Stanford acute type A aortic dissection (ATAAD) is a potentially
      lethal condition. Epidemiology studies show a statistical incidence in Europe of
      approximately 2-16 cases/100,000 inhabitants/year. In Germany, the estimated
      incidence (here subsumed under "thoracic aortic dissection" with 4.63
      cases/100,000 inhabitants/year) is mainly extracted from medical death
      certificates by the German Federal Statistical Office. The prehospital incidence
      of ATAAD deaths is largely unknown. Since patients often die in the pre-hospital
      setting, the incidence of ATAAD is therefore likely to be higher than current
      estimates. MATERIAL AND METHODS: For the period from 2010 to 2014, we
      retrospectively analyzed all in-hospital ATAAD data from two of the largest
      cardiac surgical centers that treat ATAAD in the Berlin-Brandenburg region. In
      addition, autopsy reports of all forensic medicine institutes and of one large
      pathological provider in the region were analyzed to identify additional non
      hospitalized ATAAD patients. Based on these findings, the regional incidence of
      ATAAD was calculated. RESULTS: In addition to in-hospital ATAAD patients (n=405),
      we identified additional 145 lethal ATAAD cases among 14,201 autopsy reports. The
      total of 550 ATAAD cases led to an estimated incidence of 11.9 cases/100,000
      inhabitants/year for the whole Berlin-Brandenburg region. Arterial hypertension,
      pre-existing aortic dilatation, and hereditary connective tissue disorder were
      found in, respectively, 62.7%, 10%, and 1.8% of patients. CONCLUSION: ATAAD is
      more frequent than previously reported. Our results show that when patients who
      die outside of cardiac surgery centers are included, the incidence of ATAAD
      significantly exceeds the rate reported by the Federal Statistical Office.

PMID- 28499668
TI  - A multicenter feasibility study on ultrafiltration via a single peripheral venous
      access in acute heart failure with overt fluid overload.
AB  - OBJECTIVES: The need for a central venous catheter has limited the widespread use
      of ultrafiltration in daily clinical practice for the treatment of acute heart
      failure (AHF) with overt fluid overload. We evaluated the feasibility of a new
      ultrafiltration device, the CHIARA (Congestive Heart Impairment Advanced Removal
      Approach) system, that utilizes a single-lumen cannula (17G, multi-hole) inserted
      in a peripheral vein of the arm. METHODS: In this multicenter, prospective,
      feasibility study, consecutive ultrafiltration treatments (lasting >=6 hours and
      with an ultrafiltration rate >=100ml/h) with the CHIARA device and a single
      peripheral venous approach were performed at 6 Italian hospitals. For each
      session, we evaluated the performance of the venous access, the ultrafiltrate
      volume removed, and the cause of its interruption. RESULTS: One-hundred-three
      ultrafiltration sessions were performed in 55 patients with AHF (average 1.9+/
      1.7 treatment/patient). The overall median length of ultrafiltration treatment
      was 14h (interquartile range 7-21) with removal of 3266+/-3088ml of fluid (183+/
      30ml/hour). The treatment was successfully completed in 92 (89%) sessions and in
      80% of patients. The mean suction flow rate from the vein was 70+/-20ml/min,
      while the mean re-injection flow rate was 98+/-26ml/min. There were no clinically
      relevant complications related to the venous access and/or to the anticoagulant
      therapy with heparin. CONCLUSIONS: The study demonstrated that the CHIARA system
      satisfies clinical applicability and efficacy criteria in the treatment of AHF,
      in terms of adequate fluid removal through a single peripheral venous access.

PMID- 28499669
TI  - Atorvastatin reduces cardiac and adipose tissue inflammation in rats with
      metabolic syndrome.
AB  - BACKGROUND: Statins are strong inhibitors of cholesterol biosynthesis and help to
      prevent cardiovascular disease. They also exert additional pleiotropic effects
      that include an anti-inflammatory action and are independent of cholesterol, but
      the molecular mechanisms underlying these additional effects have remained
      unclear. We have now examined the effects of atorvastatin on cardiac and adipose
      tissue inflammation in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, which we previously
      established as a model of metabolic syndrome (MetS). METHODS AND RESULTS:
      DS/obese rats were treated with atorvastatin (6 or 20mgkg-1day-1) from 9 to
      13weeks of age. Atorvastatin ameliorated cardiac fibrosis, diastolic dysfunction,
      oxidative stress, and inflammation as well as adipose tissue inflammation in
      these animals at both doses. The high dose of atorvastatin reduced adipocyte
      hypertrophy to a greater extent than did the low dose. Atorvastatin inhibited the
      up-regulation of peroxisome proliferator-activated receptor gamma gene expression
      in adipose tissue as well as decreased the serum adiponectin concentration in
      DS/obese rats. It also activated AMP-activated protein kinase (AMPK) as well as
      inactivated nuclear factor-kappaB (NF-kappaB) in the heart of these animals. The
      down-regulation of AMPK and NF-kappaB activities in adipose tissue of DS/obese
      rats was attenuated and further enhanced, respectively, by atorvastatin
      treatment. CONCLUSIONS: The present results suggest that the anti-inflammatory
      effects of atorvastatin on the heart and adipose tissue are attributable at least
      partly to increased AMPK activity and decreased NF-kappaB activity in this rat
      model of MetS.

PMID- 28499670
TI  - Feasibility and relevance of right parasternal view for assessing severity and
      rate of progression of aortic valve stenosis in primary care.
AB  - BACKGROUND: Right parasternal view (RPV) is important in assessing the severity
      of aortic stenosis (AS). However, the feasibility and relevance of RPV in primary
      care is unresolved. Moreover, information regarding the role of RPV in the
      evaluation of the hemodynamic progression of AS is lacking. METHODS: Consecutive
      patients with peak aortic valve velocity (Vmax) >=2.5m/s were prospectively
      enrolled in a primary care echocardiographic laboratory. Aortic Doppler
      parameters were evaluated from apical view and RPV. RESULTS: The total number of
      enrolled patients was 330 (aged 81+/-11years, 47% female, left ventricular
      ejection fraction 64+/-9%). The RPV was feasible in 275 (83%). Vmax and Mean
      Gradient were significantly higher and aortic valve area was significantly lower
      from RPV as compared to apical view (p<0.0001 for all). Reclassification of
      severity towards either moderate or severe AS occurred in 13-26% of patients,
      according to different criteria, when evaluated from RPV. Among 108 patients
      (40%) undergoing multiple examinations the rate of progression was lower from the
      apical approach than from the RPV (0.19+/-0.20m/s/year vs. 0.24+/-0.27m/s/year,
      respectively; p=0.03), and was fast (>0.3m/s/year) in 17 patients (16%) from the
      apical window vs. 26 patients (24%) from RPV (p<0.0001). CONCLUSION: Implementing
      RPV is feasible in primary care and results in a substantial reclassification
      rate through the entire spectrum of AS severity. Our data also suggest a
      potential role of Doppler interrogation from multiple windows to improve AS
      progression assessment.

PMID- 28499671
TI  - Tricuspid annuloplasty versus a conservative approach in patients with functional
      tricuspid regurgitation undergoing left-sided heart valve surgery: A study-level
      meta-analysis.
AB  - BACKGROUND: Tricuspid valve (TV) repair at the time of left-sided valve surgery
      is indicated in patients with either severe functional tricuspid regurgitation
      (TR) or mild-to-moderate TR with coexistent tricuspid annular dilation or right
      heart failure. We assessed the benefits of a concomitant TV repair strategy
      during left-sided surgical valve interventions, focusing on mortality and
      echocardiographic TR-related outcomes. METHODS: A meta-analysis was performed of
      studies reporting outcomes of patients who underwent left-sided (mitral and/or
      aortic) valve surgery with or without concomitant TV repair. Primary endpoints
      were all-cause and cardiac-related mortality; secondary endpoints were the
      presence of more-than-moderate TR, TR progression, and TR severity grade. All
      endpoints were evaluated at the longest available follow-up. RESULTS: Fifteen
      studies were included for a total of 2840 patients. TV repair at the time of left
      sided valve surgery was associated with a significantly lower risk of cardiac
      related mortality (odds ratio [OR] 0.38; 95% confidence interval [CI]: 0.25-0.58;
      p<0.001), with a trend towards a lower risk of all-cause mortality (OR 0.57; 95%
      CI: 0.32-1.05; p=0.07) at a mean weighted follow-up of 6years. The presence of
      more-than-moderate TR (OR 0.19; 95% CI: 0.12-0.30; p<0.001), TR progression (OR
      0.03; 95% CI: 0.01-0.05; p<0.001), and TR grade (standardized mean difference 
      1.11; 95% CI: -1.57 to -0.65; p<0.001) were significantly lower in the TV repair
      group at a mean weighted follow-up of 4.7years. CONCLUSIONS: A concomitant TV
      repair strategy during left-sided valve surgery is associated with a reduction in
      cardiac-related mortality and improved echocardiographic TR outcomes at follow
      up.

PMID- 28499672
TI  - Association of elevated pulmonary artery systolic pressure with stroke and
      systemic embolic events in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Echocardiographically estimated pulmonary artery systolic pressure
      (PASP) is a non-invasive widely available method that is used to estimate
      pulmonary arterial pressure. Although elevated PASP predicts mortality in
      patients with hypertrophic cardiomyopathy (HCM), the relationship between PASP
      and embolic events is unclear. This study aimed to determine whether elevated
      PASP is associated with stroke and systemic embolic events in a tertiary referral
      HCM cohort. METHODS: This study included 374 clinically diagnosed patients with
      HCM. PASP was estimated from tricuspid regurgitant jet velocity using the
      modified Bernoulli equation. RESULTS: The median (interquartile range) PASP was
      33 (28-37) mm Hg, and elevated PASP (>40mmHg) was observed in 66 (17.6%)
      patients. Seventeen of the 66 (25.8%) patients with elevated PASP and 24 of the
      308 (7.8%) patients without elevated PASP experienced stroke and systemic embolic
      events during the 10.3+/-7.4years of follow-up (log-rank P<0.001). Multivariable
      analysis showed that age at diagnosis, atrial fibrillation, and PASP >40mmHg
      (adjusted hazard ratio, 2.59; 95% confidence interval, 1.31-5.12; P=0.006) were
      independently associated with embolic events. CONCLUSIONS: In addition to age and
      atrial fibrillation, PASP estimated by Doppler echocardiography could help
      embolic risk stratification in patients with HCM.

PMID- 28499673
TI  - [How I do... to perform uterine adenomyomectomy].

PMID- 28499674
TI  - [Training of residents in amniocentesis: Effectiveness of a craft simulator].
AB  - OBJECTIVE: This prospective study aims to assess a low fidelity simulation device
      for learning amniocentesis to gynecology-obstetrics residents. METHODS: From 2013
      to 2016, gynecology-obstetrics residents of all levels, from the maternity of
      Nancy hospital, which have already performed amniocentesis or not, participated
      in amniocentesis training on an artisanal simulator. Residents were evaluated on
      the amniocentesis simulator according to seven quality criteria. Three scores
      were assigned: the first (S1) at the beginning of the first training session, the
      second (S2) at the end of the first session after individualized personal
      training and the third (S3) two months after the first simulation. RESULTS: A
      total of 40 residents were included. The scores obtained by the residents were
      3.2+/-1.8 points for S1 versus 6.2+/-0.9 points for S2 (P<0.001). Two months
      after, the residents' performances remained significantly improved compared to
      the initial assessment with a score (S3) of 5.8+/-1.3 points at S3 (P<0.001).
      CONCLUSION: Amniocentesis craft simulator is effective for performance
      improvement and allows a persistence of acquired skills two months after the
      training. At the time of "never the first time on the patient", it should be part
      of the curriculum of gynecology-obstetrics residents in order to guarantee
      patients quality care and optimum safety.

PMID- 28499675
TI  - Growth and Psychological Development in Postoperative Patients With Anterior
      Encephaloceles.
AB  - PURPOSE: Anterior encephaloceles are rare malformations that are frequently
      associated with other brain anomalies. This study evaluates the growth and
      psychological development of children following encephalocele repair. MATERIALS &
      METHODS: Growth and psychological assessment was done in 24 children with only
      encephalocele (group I); nine children with encephalocele and hydrocephalus
      (group II); seven children with encephalocele, hydrocephalus, and secondary
      malformations (group III); and 40 apparently healthy control subjects.
      Psychological assessment was done by evaluating intelligence and temperament.
      RESULTS: Single-stage repair was performed in 38 children, and two underwent
      multistage repair. Major postoperative complications were noted in three
      individuals. The follow-up period ranged from 12 to 168 months, and during this
      time the growth velocity declined significantly among group II and group III
      patients when compared with control subjects. After adjusting the body mass index
      for age, our data revealed that group III participants had a significantly (P =
      0.02) lower body mass index than the control group. Group III also had poor
      indices for intelligence quotient (P <= 0.01) and temperament (P <= 0.01). Female
      patients had lower temperament indices when compared with unaffected females with
      regard to approach withdrawal (P <= 0.01), mood (P = 0.026), and intensity (P =
      0.03). Overall, increased disease severity adversely affected the psychological
      indices. CONCLUSION: Individuals with anterior encephalocele without associated
      intracranial defects had excellent postoperative outcomes in terms of growth and
      psychological developments. Hydrocephalus and agenesis of corpus callosum had the
      least impact on psychological development. However, the presence of secondary
      brain defects led to developmental delays. Gender differences in temperament may
      suggest a need for distinct treatment regimens to assess psychosocial well-being
      for males and females.

PMID- 28499678
TI  - Saving Lives for 35 Years: Sentara Nightingale Looks Forward.
AB  - The Nightingale Regional air Ambulance program, operated by Norfolk, VA-based not
      for-profit Sentara Healthcare, is marking its 35th year of operation in 2017,
      having surpassed 20,000 safe flights. Looking ahead, the program is adding IFR
      capabilities, designated landing zones to rendezvous with EMS partners and
      clinical training in a simulation lab, and collaborating with cardiac and
      neurology services to provide quicker interventions for STEMI and stroke patients
      at Sentara Norfolk General Hospital.

PMID- 28499679
TI  - Aeromedical Ultrasound: The Evaluation of Point-of-care Ultrasound During
      Helicopter Transport.
AB  - INTRODUCTION: This study correlated the eFAST findings performed in-flight by the
      flight crew with the findings obtained by the trauma team upon initial evaluation
      at a level 1 trauma center and with the subsequent CT scans that were performed
      or the surgeon's operative note. We hypothesize that aeromedical eFAST
      examinations are highly correlated with the trauma teams findings. METHODS: This
      prospective, observational study evaluated 190 traumatically injured patients
      from June 2014 to December 2015 in Southeast Virginia and Northeast North
      Carolina. RESULTS: For 190 trauma patients the Flight Crew POCUS examinations
      obtained a Positive Predictive Value (PPV) of 100% and a Negative Predictive
      Value (NPV) of 98.3% for the identification of pneumothorax, hemothorax, and free
      abdominal fluid, which is equivalent to that of the Trauma Team's POCUS studies
      on the same group of patients. DISCUSSION: Because the early recognition of
      potentially life-threatening conditions is critical to providing appropriate care
      to the traumatically injured patient this study provides solid statistical data
      that flight crews can adequately perform and interpret POCUS results as well as
      out trauma team colleagues. This study could lead to a reduction of iatrogenic
      injuries from unnecessary invasive prehospital procedures, allow for early
      initiation of Massive Transfusion Protocols (MTP) prior to the patient's arrival
      at the Trauma Center, and potentially develop a change in trauma systems
      notification and transportation directly to the operating room. CONCLUSION:
      Despite this study developing a very positive outlook on performing aeromedical
      POCUS for the evaluation and care of trauma patients additional research will be
      required to better understand the potential impact on trauma activation protocols
      and activation of in-hospital resources.

PMID- 28499680
TI  - A Systematic Review of the Prevalence and Types of Adverse Events in
      Interfacility Critical Care Transfers by Paramedics.
AB  - OBJECTIVE: The aim of this study was to investigate if paramedics can safely
      transfer interfacility critically ill adult patients and to determine the
      prevalence and types of adverse events when paramedics lead interfacility
      critical care transfers. METHODS: MEDLINE, Web of Science, Embase, and CINAHL
      databases were searched from 1990 up to February 2016. Eligibility criteria were
      adult patients (16 years and over), interfacility transfer (between two health
      care facilities), quantitative or qualitative description of adverse events, and
      a paramedic as the primary care provider or the sole health care provider.
      RESULTS: Seven publications had paramedics as the sole health care provider
      conducting interfacility critical care transfers. All seven studies were
      observational studies published in the English language. The study duration
      ranged from 14 months to 10 years. The frequency of adverse events seen by
      paramedics in interfacility transfers ranges from 5.1% to 18%. CONCLUSION: There
      is a gap in literature on the safety and adverse events in interfacility
      transfers by paramedics. The prevalence of in-transit adverse events is well
      established; however, because the published literature is lacking longitudinal
      monitoring of patients and only reporting in-transit events, we believe that
      further research in this area might provide the basis of paramedics safety in
      interfacility transfers.

PMID- 28499681
TI  - Is Nifedipine as a Tocolytic Effective in Facilitating In Utero Transfer?
AB  - OBJECTIVE: Previous studies have reported that air medical transfer of women in
      preterm labor can be safely accomplished, without preterm birth occurring; in
      fact, many women were later discharged without preterm birth occurring. The
      purpose of this study was to determine if nifedipine, when used as a tocolytic,
      is effective at facilitating in utero transfer of women in preterm labor in the
      Top End of the Northern Territory of Australia. METHODS: This was a retrospective
      descriptive study over a 3-year period of all women transported in preterm labor
      between 23 + 6 to 36 + 6 weeks' gestation of pregnancy (N = 325). RESULTS: The
      average gestation period was 32 + 2 weeks. The mean retrieval time was 6 hours.
      The mean time of birth from referral was 33 hours. A number of women gave birth
      to a preterm newborn in a remote health center (17%). There were 3 in-flight
      preterm births, and 49% of women were discharged without a preterm birth
      occurring. All women transported by air medical retrieval were admitted to the
      tertiary hospital for at least 24 hours. CONCLUSION: In this study, nifedipine
      was used successfully to facilitate in utero transfer in many cases. Nearly half
      of the women referred were discharged without preterm birth occurring. Findings
      compare favorably with other published studies.

PMID- 28499682
TI  - An Analysis of the Temperature Change in Warmed Intravenous Fluids During
      Administration in Cold Environments.
AB  - This nonhuman simulation study was conducted to determine the decrease in
      temperature that occurred to 1-L bags of normal saline in a cold environment. The
      bags were warmed to 39 degrees C and administered through intravenous (IV) tubing
      at a set flow rate while in a cold environment. The goal was to determine if
      there was a significant decrease in fluid temperature from the bag to the
      catheter site. Three trials were completed at temperatures of 0 degrees C, -7
      degrees C, -12 degrees C, and 22 degrees C (control). Each bag of normal saline
      was warmed to 39 degrees C using the SoftSack IV Fluid Warmer (Smithworks Med
      Inc, Lindale, TX). Fluid was collected and temperatures recorded at 5-minute
      intervals. The results showed a statistically significant (P = .003) change in
      temperature between the IV bag and the administration site. The most rapid change
      occurred within the first 5 minutes. The temperature change was more significant
      with colder ambient temperatures, with an average of a 28.7 degrees C difference
      at -7 degrees C and -12 degrees C after 30 minutes. It appears that the most
      significant heat loss occurs through the IV tubing itself. Therefore, it may be
      beneficial to insulate the tubing on a trauma patient receiving warmed IV fluids
      in a cold environment to help prevent hypothermia.

PMID- 28499683
TI  - Response of Flight Nurses in a Simulated Helicopter Environment.
AB  - OBJECTIVE: The purpose of this study was to determine if a helicopter flight
      simulator could provide a useful educational platform by creating experiences
      similar to those encountered by actual flight nurses. METHODS: Flight nurse (FN)
      and non-FN participants completed a simulated emergency scenario in a flight
      simulator. Physiologic and psychological stress during the simulation was
      measured using heart rate and perceived stress scores. A questionnaire was then
      administered to assess the realism of the flight simulator. RESULTS: Subjects
      reported that the overall experience in the flight simulator was comparable with
      a real helicopter. Sounds, communications, vibrations, and movements in the
      simulator most approximated those of a real-life helicopter environment.
      Perceived stress levels of all participants increased significantly from 27 (on a
      0-100 scale) before simulation to 51 at the peak of the simulation and declined
      thereafter to 28 (P < .001). Perceived stress levels of FNs increased
      significantly from 25 before simulation to 54 at the peak of the simulation and
      declined thereafter to 30 (P < .001). Perceived stress levels of non-FNs
      increased significantly from 31 before simulation to 49 at the peak of the
      simulation and declined thereafter to 25 (P < .001). There were no significant
      differences in perceived stress levels between FNs and non-FNs before (P = .58),
      during (P = .63), or after (P = .55) simulation. FNs' heart rates increased
      significantly from 77 before simulation to 100 at the peak of the simulation and
      declined thereafter to 72 (P < .001). CONCLUSION: The results of this study
      suggest that simulation of a critical care scenario in a high-fidelity helicopter
      flight simulator can provide a realistic helicopter transport experience and
      create physiologic and psychological stress for participants.

PMID- 28499684
TI  - Flying Lessons for Clinicians: Developing System 2 Practice.
AB  - There is a long history of adopting lessons learned from aviation to improve
      health care practice. Two of the major practices that have successfully
      transferred include using a checklist and simulation. Training and simulation
      technology is currently underdeveloped for nurses and health care providers
      entering critical care transport. This article describes a pedagogical approach
      adopted from aviation to develop a new simulation platform and program of
      research to develop the science of critical care transport nursing education.

PMID- 28499685
TI  - Ultrasound in the Royal Danish Air Force Search and Rescue Helicopter: 2 Case
      Reports.

PMID- 28499686
TI  - An Unusual Case of Shortness of Breath.

PMID- 28499688
TI  - In Memoriam.

PMID- 28499687
TI  - Erratum to 'Air Medical Evacuations From the German North Sea Wind Farm Bard
      Offshore 1: Traumatic Injuries, Acute Diseases, and Rescue Process Times (2011
      2013)' [Air Medical Journal 35 (2016) 216-226].

PMID- 28499689
TI  - An 89-Year-Old Man Hanging in a Remote Location.

PMID- 28499690
TI  - Weaning.

PMID- 28499691
TI  - Good People Don't Smoke Marijuana.

PMID- 28499692
TI  - Genital discomfort: yeast, trichomonas and bacterial vaginosis are only the tip
      of the iceberg.

PMID- 28499693
TI  - A case report of mysterious bleeding.

PMID- 28499694
TI  - Effectiveness and safety of community-based treatment with sofosbuvir plus
      ribavirin for elderly patients with genotype 2 chronic hepatitis C.
AB  - BACKGROUND: The aim of this study was to clarify the effectiveness and safety of
      sofosbuvir/ribavirin therapy for elderly patients with genotype 2-infected
      chronic hepatitis C (CHC) in Japan. METHODS: A multicenter, retrospective study
      evaluated the effectiveness and safety of sofosbuvir/ribavirin based on real
      world clinical data. RESULTS: The subjects consisted of 270 patients, 47.0% of
      whom were aged >=65 years. The sustained virological response rates in patients
      aged <65 and >=65 years were 98.6% and 95.3%, respectively. Hemoglobin levels
      decreased during treatment due to ribavirin-related hemolysis, and were
      significantly lower in patients aged >=65 years than those aged <65 years at all
      time-points. A reduction in ribavirin dose was necessary in 31.0% (26/84) of
      patients with hemoglobin levels <13.0g/dL and in 70.7% (39/127) of those aged >65
      years. Although the most frequent adverse event was anemia, no patients
      discontinued the use of either ribavirin or sofosbuvir. The incidence of
      ribavirin-related anemia in patients aged >=65 years was 34.6% and significantly
      higher compared with that in patients aged <65 years (2.8%). CONCLUSIONS:
      Treatment with sofosbuvir/ribavirin for genotype 2-infected CHC was effective and
      safe even for elderly patients, although the incidence of adverse events
      including ribavirin-related anemia was relatively high.

PMID- 28499695
TI  - Dapagliflozin modulates glucagon secretion in an SGLT2-independent manner in
      murine alpha cells.
AB  - AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent
      mechanism. They also increase glucagon concentration, although the extent to
      which this is due to a direct effect on pancreatic alpha cells remains unclear.
      METHODS: In the present work, alphaTC1 cells treated with the SGLT2 inhibitor
      dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators
      of hormone secretion, glucagon and GLP-1 release, and the effects of
      somatostatin. Data were validated in murine and human pancreatic islets. RESULTS:
      SLC5A2 (the SGLT2-encoding gene) was nearly undetectable in alphaTC1 cells, not
      even by a digital PCR technique using different probes. In contrast, SLC5A1 (the
      SGLT1-encoding gene) was constitutively abundant in alphaTC1 cells and in islets,
      and increased with Dapa. This was associated with greater glucagon release,
      preceded by increased expression of preproglucagon and HNF4alpha. Looking at the
      candidate intracellular signalling pathway, reduced PASK and increased AMPK
      alpha2 expression were also detected. GLUT1 and GLUT2, as well as regulators of
      glucagon release and alpha-cell phenotype (chromogranin A, paired box 6,
      proprotein convertase 1/2, synaptophysin), were unaffected by Dapa, as were GLP-1
      receptor expression and GLP-1 release. Low glucose did not influence the
      stimulatory effect of Dapa on glucagon release, but was instead almost fully
      reverted by SLC5A1 silencing. When the effect of Dapa on AMPK and PASK, emerging
      regulators of lipid and glucose metabolism, was tested, upregulated AMPK-alpha2
      appeared to be involved in molecular signalling. CONCLUSION: Our study has shown
      that, in alphaTC1 cells, Dapa acutely upregulates SGLT1 expression and increases
      glucagon release through an SGLT1-dependent mechanism, with SGLT2 expression
      virtually undetectable. These results suggest the involvement of SGLT1 in
      modulating glucagon increases following SGLT2 inhibition.

PMID- 28499697
TI  - Assessment of dietary compliance in celiac children using a standardized dietary
      interview.
AB  - BACKGROUND & AIMS: Compliance to a gluten free diet (GFD) in celiac disease (CD)
      is ideally assessed by dietary interviews, albeit time-consuming. Short dietary
      questionnaires have been developed for adults but not for children. Primary aim
      was to compare GFD compliance in celiac children, measured by a short dietary
      questionnaire against a dietary interview. Secondary aims were correlation
      between both questionnaires and celiac antibodies and identifying variables
      predicting noncompliance. METHODS: Between 2012 and 2014, participants in the E
      health CoelKids study, completed a short dietary questionnaire and standardized
      dietary interview together with measurement of anti-tissue transglutaminase
      antibodies (TG2A). Results of the questionnaires were assigned under similar
      categories. Factors possibly influencing dietary compliance were recorded. Where
      appropriate, Pearson's Chi-square test for trend, unpaired t-test, Cohen's kappa
      and one-way ANOVA were used. RESULTS: 151 of 165 participating patients were
      studied, 66% were female. Mean age was 11.3 years (2-26, SD 5.4), mean age at CD
      diagnosis was 4.9 years (1-23, SD 4.0). The short questionnaire and dietary
      interview correlated poorly, detecting problems in dietary adherence in 14% and
      52% of the patients, respectively (Cohen's kappa 0.034). Only the short
      questionnaire correlated with TG2A (p = 0.003). Only older age was associated
      with noncompliance, the mean age of completely nonadherent, adherent but
      committing errors, and strictly adherent patients were 15.5, 11.5 and 10.1 years,
      respectively (p < 0.001). CONCLUSIONS: Compared to the dietary interview, short
      dietary questionnaires and TG2A serology failed to detect dietary transgressions
      in CD children, wherein adolescents were shown to be at highest risk.

PMID- 28499696
TI  - Fenofibrate decreases plasma ceramide in type 2 diabetes patients: A novel marker
      of CVD?
AB  - AIM: The benefit of the lipid-lowering drug fenofibrate on cardiovascular
      outcomes is controversial. Our aim was to find new circulating markers to
      identify those patients most likely to benefit from fenofibrate prescription.
      METHODS: Analyses were conducted of plasma samples collected from 102 patients
      with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate
      treatment (200mg/day). Non-targeted and targeted lipid analyses and
      apolipoprotein measurements were made using mass spectrometry methods. RESULTS:
      Lipidomics revealed a global decrease in ceramide after fenofibrate treatment
      confirmed by quantitative analysis (-18.2%, P<0.001). These changes were strongly
      associated with those found for plasma sphingomyelin (r=0.80, P<0.001) and, to a
      lesser extent, for sphingosine-1-phosphate (r=0.34, P<0.001). Ceramide levels
      decreased in 73.5% of patients. In addition to the expected lipid changes
      (decreases in triglycerides, total cholesterol and LDL cholesterol, and increase
      in HDL cholesterol), fenofibrate also lowered plasma apoC-II (-11.1%, P<0.01),
      apoC-III (-24.6%; P<0.001), apoB100 (-27.0%, P<0.01) and sphingomyelinase (-7.6%,
      P<0.001), and increased plasma apoA-II (22.4%, P<0.001) as well as adiponectin
      (11.4%, P<0.001). No significant association was found between ceramide decrease
      and these modulations except for total cholesterol (r=0.20, P=0.047) and HDL
      protein components. At baseline, only elevated sphingolipid levels were
      significantly associated with ceramide reduction after fenofibrate treatment.
      CONCLUSION: Fenofibrate lowers plasma ceramide independently of the usual lipid
      parameters. As ceramide is a strong marker of atherosclerosis, our study
      underpins the need to further evaluate its contribution to cardiovascular events
      in fenofibrate-treated patients.

PMID- 28499698
TI  - Dental microwear and Pliocene paleocommunity ecology of bovids, primates,
      rodents, and suids at Kanapoi.
AB  - Reconstructions of habitat at sites like Kanapoi are key to understanding the
      environmental circumstances in which hominins evolved during the early Pliocene.
      While Australopithecus anamensis shows evidence of terrestrial bipedality
      traditionally associated with a more open setting, its enamel has low delta13C
      values consistent with consumption of C3 foods, which predominate in wooded areas
      of tropical Africa. Habitat proxies, ranging from paleosols and their carbonates
      to associated herbivore fauna and their carbon isotope ratios, suggest a
      heterogeneous setting with both grass and woody plant components, though the
      proportions of each have been difficult to pin down. Here we bring dental
      microwear texture analysis of herbivorous fauna to bear on the issue. We present
      texture data for fossil bovids, primates, rodents, and suids (n = 107 individuals
      in total) from the hominin bearing deposits at Kanapoi, and interpret these in
      the light of closely related extant mammals with known differences in diet. The
      Kanapoi bovid results, for example, are similar to those for extant variable
      grazers or graze-browse intermediate taxa. The Kanapoi suid data vary by taxon,
      with one similar to the pattern of extant grazers and the other more closely
      resembling mixed feeders. The Kanapoi primates and rodents are more difficult to
      associate with a specific environment, though it seems that grass was likely a
      component in the diets of both. All taxa evince microwear texture patterns
      consistent with a mosaic of discrete microhabitats or a heterogeneous setting
      including both tree and grass components.

PMID- 28499699
TI  - Malaria Vector Control Still Matters despite Insecticide Resistance.
AB  - Mosquito vectors' resistance to insecticides is usually considered a major threat
      to the recent progresses in malaria control. However, studies measuring the
      impact of interventions and insecticide resistance reveal inconsistencies when
      using entomological versus epidemiological indices. First, evaluation tests that
      do not reflect the susceptibility of mosquitoes when they are infectious may
      underestimate insecticide efficacy. Moreover, interactions between insecticide
      resistance and vectorial capacity reveal nonintuitive outcomes of interventions.
      Therefore, considering ecological interactions between vector, parasite, and
      environment highlights that the impact of insecticide resistance on the malaria
      burden is not straightforward and we suggest that vector control still matters
      despite insecticide resistance.

PMID- 28499700
TI  - Imatinib mesylate- and dasatinib-induced eosinophilia in a patient with chronic
      myelocytic leukemia.

PMID- 28499701
TI  - Should We Stop Saying 'Glia' and 'Neuroinflammation'?
AB  - Central nervous system (CNS) therapeutics based on the theoretical framework of
      neuroinflammation have only barely succeeded. We argue that a problem may be the
      wrong use of the term 'neuroinflammation' as a distinct nosological entity when,
      based on recent evidence, it may not explain CNS disease pathology. Indeed, the
      terms 'neuroinflammation' and 'glia' could be obsolete. First, unbiased molecular
      profiling of CNS cell populations and individual cells reveals striking
      phenotypic heterogeneity in health and disease. Second, astrocytes, microglia,
      oligodendrocytes, and NG2 cells may contribute to higher-brain functions by
      performing actions beyond housekeeping. We propose that CNS diseases be viewed as
      failed circuits caused in part by disease-specific dysfunction of cells
      traditionally called 'glia', and hence, favor therapies promoting their
      functional recovery.

PMID- 28499702
TI  - Prespermatogenesis and early spermatogenesis in frogs.
AB  - Spermatogenesis in frogs was for the first time divided into two phases:
      prespermatogenesis, when gonocytes proliferate in developing tadpole testes, and
      active spermatogenesis when spermatogonial stem cells (i.e. descendants of
      gonocytes), either self-renew or enter into meiotic cycles within cysts formed by
      Sertoli cells. We argue that amphibian larval gonocytes are homologues to
      mammalian gonocytes, whereas spermatogonial stem cells (SSCs) in adult frogs are
      homologous to mammalian single spermatogonia (As). Gonocytes constitute sex
      cords, i.e. the precursors of seminiferous tubules; they are bigger than SSCs and
      differ in morphology and ultrastructure. The nuclear envelope in gonocytes formed
      deep finger-like invaginations absent in SSCs. All stages of male germ cells
      contained lipid droplets, which were surrounded by glycogen in SSCs, but not in
      gonocytes. Mitochondria in gonocytes had enlarged edges of cristae, and in SSCs
      also lamellar mitochondria appeared. Minimal duration of prespermatogenesis was
      46days after gonadal sex differentiation, but usually it lasted longer. SSCs give
      rise to secondary spermatogonia (equal to mammalian A, In, and B). Their lowest
      number inside a cyst was eight and this indicated the minimal number of cell
      cycles (three) of secondary spermatogonia necessary to enter meiosis. We sorted
      them according to the number of cell cycles (from 8 to 256 cells). This number is
      similar to that recorded for mammals as the result of a single As proliferation.
      The number of secondary spermatogonia correlates with the volume of a cyst. The
      general conclusion is that spermatogenesis in amphibians and mammals follows
      basically the same scheme.

PMID- 28499704
TI  - Displaced Endoscopic Ultrasound-Guided Gastroenterostomy Stent Rescued With
      Natural Orifice Transluminal Endoscopic Surgery.

PMID- 28499703
TI  - miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin.
AB  - Invasion is a hallmark of advanced head and neck squamous cell carcinoma (HNSCC).
      We previously determined that low relative miR-375 expression was associated with
      poor patient prognosis. HNSCC cells with increased miR-375 expression have lower
      invasive properties and impaired invadopodium activity. Using stable isotope
      labeling with amino acids in cell culture and reverse-phase liquid chromatography
      mass spectrometry, we assessed the impact of miR-375 expression on protein levels
      in UM-SCC-1 cells. Increased miR-375 expression was associated with down
      regulation of proteins involved in cellular assembly and organization, death and
      survival, and movement. Two invasion-associated proteins, vimentin and L-plastin,
      were strongly down-regulated by miR-375. Luciferase reporter assays demonstrated
      that high miR-375 expression reduced vimentin promoter activity, suggesting that
      vimentin is an indirect target of miR-375. Runt-related transcription factor 1
      (RUNX1) is a potential miR-375 direct target, and its knockdown reduced vimentin
      and L-plastin expression. Data in The Cancer Genome Atlas HNSCC database showed a
      significant inverse correlation between miR-375 expression and RUNX1, vimentin,
      and L-plastin RNA expression. These clinical correlations validate our in vitro
      model findings and support a mechanism in which miR-375 suppresses RUNX1 levels,
      resulting in reduced vimentin and L-plastin expression. Furthermore, knockdown of
      RUNX1, L-plastin, and vimentin resulted in significant reductions in cell
      invasion in vitro, indicating the functional significance of miR-375 regulation
      of specific proteins involved in HNSCC invasion.

PMID- 28499706
TI  - Pseudophakic Macular Edema in Primary Open-Angle Glaucoma: A Prospective Study
      Using Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: To determine the incidence of and risk factors for pseudophakic macular
      edema (PME) after uncomplicated cataract surgery in primary open-angle glaucoma
      (POAG) using spectral-domain optical coherence tomography (SDOCT). DESIGN: Cohort
      study. METHODS: Macular retinal thickness was evaluated using SDOCT at 1 week
      before surgery and at 1, 3, 6, and 12 months postoperatively, in 70 POAG and 68
      control eyes. Forty-three healthy subjects without impaired vision or cystoid PME
      were recruited separately as pilot samples to define significant PME. Significant
      PME was defined as an increase in the average thickness exceeding the mean + 3
      standard deviations of the increase shown in the pilot samples. RESULTS:
      Significant PME (increase in the foveal 3-mm zone thickness of >19.5 MUm) was
      observed in 31 (44%) eyes with POAG and in 14 (21%) control eyes (P = .003). The
      extent of PME was maximal at 3 months postoperatively and decreased gradually
      until 12 months. Regression tree analysis revealed that the risk of PME was the
      greatest in the POAG group using prostaglandin analogue (PGA) (odds ratio [OR] =
      5.51), followed by POAG not using PGA (OR = 1.70), and control group (OR = 1.0).
      Risk factors for PME were younger age in all groups (OR = 1.07), systemic
      hypertension in PGA users (OR = 6.42), higher untreated IOP in PGA nonusers (OR =
      1.09) and male sex (OR = 14.06) and diabetes mellitus (OR = 16.71) in the control
      group. CONCLUSIONS: The incidence of PME as observed by SDOCT was higher than
      previously reported after uncomplicated cataract surgery. Eyes with POAG were at
      greater risk for PME, which was mainly associated with perioperative PGA use.

PMID- 28499705
TI  - Measurement and Reproducibility of Preserved Ellipsoid Zone Area and Preserved
      Retinal Pigment Epithelium Area in Eyes With Choroideremia.
AB  - PURPOSE: To identify valid and reproducible methods for quantifying anatomic
      outcome measures for eyes with choroideremia (CHM) in clinical trials. DESIGN:
      Reliability analysis study. METHODS: In this multicenter study, patients with
      confirmed genetic diagnosis of CHM were enrolled. All cases underwent spectral
      domain optical coherence tomography (SDOCT) and fundus autofluorescence (FAF)
      imaging. Two graders independently delineated boundaries of preserved
      autofluorescence (PAF) and preserved ellipsoid zone (EZ) on FAF and OCT images,
      respectively. The results of the 2 independent gradings of both FAF and OCT
      images were compared to assess the reproducibility of the grading methods.
      RESULTS: A total of 148 eyes from 75 cases were included. In 21% of eyes PAF and
      in 43% of eyes preserved EZ had extended beyond the image capture area. After
      exclusion of these eyes and low-quality images, 114 FAF and 77 OCT images were
      graded. The mean PAF areas from 2 independent gradings were 3.720 +/- 3.340 mm2
      and 3.692 +/- 3.253 mm2, respectively. Intraclass correlation coefficient (ICC)
      for these gradings was 0.996. The mean preserved EZ areas from 2 independent
      gradings were 2.746 +/- 2.319 mm2 and 2.858 +/- 2.446 mm2, respectively. ICC for
      these gradings was 0.991. CONCLUSIONS: Quantifying preserved retinal pigment
      epithelium and EZ areas on FAF and OCT images, respectively, in CHM patients is
      highly reproducible. These variables would be potential anatomic outcome measures
      for CHM clinical trials and could be studied and tracked longitudinally in
      choroideremia.

PMID- 28499707
TI  - Lower Laser Energy Levels Lead to Better Visual Recovery After Small-Incision
      Lenticule Extraction: Prospective Randomized Clinical Trial.
AB  - PURPOSE: To determine the effect of lowering laser energy on clinical outcomes in
      small-incision lenticule extraction (SMILE). DESIGN: Prospective randomized
      clinical trial. METHODS: A total of 151 patients (151 eyes) with moderate myopia
      scheduled for SMILE were included: 58 eyes received SMILE with low energy (100,
      105, and 110 nJ; L-SMILE group) and 93 with conventional energy (115-150 nJ; C
      SMILE group). Patients received complete ophthalmic examinations preoperatively
      and over 3 months postoperatively. RESULTS: Uncorrected distance visual acuity
      (logMAR UDVA) 1 day and 1 week postoperatively was significantly better in L
      SMILE than in C-SMILE (P < .001 and P = .005, respectively). There was no
      significant difference between the groups at 1 and 3 months. L-SMILE induced
      significantly fewer corneal aberrations compared with C-SMILE at 1 week and 1
      month postoperatively (both P < .01), but there were no significant differences
      at 3 months. Though there was no difference in logMAR UDVA over the postoperative
      period between the 100, 105, and 110 nJ subgroups, there was a significant
      difference in logMAR UDVA on postoperative day 1 between L-SMILE and each
      subgroup in which an energy level of 115 nJ or higher was used. Furthermore,
      logMAR UDVA on postoperative day 1 showed a significant correlation with laser
      energy (r = 0.451, P < .001) and multiple linear regression analysis revealed
      that energy level was the only independent factor associated with logMAR UDVA on
      postoperative day 1 (P < .001). CONCLUSIONS: SMILE using femtosecond energy of
      less than 115 nJ facilitates better visual acuity with less induction of corneal
      aberrations in the early postoperative period.

PMID- 28499708
TI  - Incidence of Intermediate-stage Age-related Macular Degeneration in Patients With
      Acquired Immunodeficiency Syndrome.
AB  - PURPOSE: To evaluate the incidence of intermediate-stage age-related macular
      degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS).
      DESIGN: Cohort study. METHODS: Patients enrolled in the Longitudinal Study of the
      Ocular Complications of AIDS (LSOCA) underwent 5- and 10-year follow-up retinal
      photographs. Intermediate-stage AMD (AREDS stage 3) was determined from these
      photographs by graders at a centralized Reading Center, using the Age-Related Eye
      Disease Study-2 grading system. The incidence of AMD in LSOCA was compared with
      that in the Multi-Ethnic Study of Atherosclerosis (MESA), a Human
      Immunodeficiency Virus (HIV)-uninfected cohort, which used a similar photographic
      methodology. RESULTS: The incidence of AMD in LSOCA was 0.65/100 person-years
      (PY). In a multivariate analysis the only significant risk factor for AMD in
      LSOCA was smoking; the relative risk vs never-smokers was 3.4 for former smokers
      (95% confidence interval [CI] 1.3, 9.5; P = .02) and 3.3 for current smokers (95%
      CI 1.1, 9.7; P = .03). Compared with the MESA cohort, the race/ethnicity- and sex
      adjusted risk of AMD in LSOCA was 1.75 (95% CI 1.16, 2.64; P = .008), despite the
      fact that the mean age of the MESA cohort was 17 years greater than the LSOCA
      cohort (61 +/- 9 years vs 44 +/- 8 years). CONCLUSIONS: Patients with AIDS have a
      1.75-fold increased race- and sex-adjusted incidence of intermediate-stage AMD
      compared with that found in an HIV-uninfected cohort. This increased incidence is
      consistent with the increased incidence of other age-related diseases in
      antiretroviral-treated, immune-restored, HIV-infected persons when compared with
      HIV-uninfected persons.

PMID- 28499709
TI  - Mortality in dialysis patients with cinacalcet use: A large observational
      registry study.
AB  - BACKGROUND: Secondary hyperparathyroidism (sHPT) is associated with higher
      mortality in dialysis patients. The calcimimetic cinacalcet reduces intact
      parathyroid hormone (iPTH) in dialysis patients. The randomized controlled EVOLVE
      trial failed to unequivocally prove survival advantage of cinacalcet in dialysis
      patients. However, recent post hoc analyses suggested a benefit in subgroups of
      dialysis patients. Large observational cohort studies may represent an option to
      better determine such subgroups. METHODS: Data from the nationwide Austrian
      registry of dialysis patients between January 2004 and December 2009 were
      analyzed with follow-up until December 2010. All-cause and cardiovascular
      mortality analyses were performed using the Kaplan-Meier and Cox proportional
      hazards regression. To reduce confounding effects a propensity score (PS) based
      method (matching by stratification) was used for group comparison. RESULTS: The
      cohort included 7983 dialysis patients, 1572 (19.7%) were prescribed cinacalcet.
      During a median follow-up of 2.7years, 3574 (44.8%) patients died, including 1342
      (16.8%) deaths from cardiovascular causes. Survival analyses in the PS-matched
      study population (n=6109) showed lower all-cause mortality for cinacalcet-treated
      as compared to untreated patients only in subsets characterized by younger age,
      low prevalence of diabetes, iPTH levels between 300 and 599pg/mL, concomitant
      therapy with vitamin D and phosphate binders. CONCLUSIONS: Our data suggest that
      a subgroup of dialysis patients, namely those with moderate sHPT, younger age and
      without diabetes benefit from cinacalcet with reduced overall and cardiovascular
      mortality. These findings may help to identify populations for further controlled
      trials and may allow a more individualized sHPT treatment using cinacalcet in
      specific patient subgroups.

PMID- 28499710
TI  - Impact of prealbumin on mortality and hospital readmission in patients with acute
      heart failure.
AB  - BACKGROUND: Prealbumin is a maker of nutritional status and inflammation of
      potential prognostic value in acute heart failure (HF). The aim of this study is
      to evaluate if low prealbumin levels on admission predict mortality and
      readmissions in patients with acute HF. METHOD: We conducted a prospective
      observational cohort study including 442 patients hospitalized for acute HF.
      Patients were classified in two groups according to prealbumin levels: "normal"
      prealbumin (>15mg) and "low" prealbumin (<=15mg/dL). End-points were mortality
      and readmissions (all-cause and HF-related) and the combined end-point of
      mortality/readmission at 180days. RESULTS: Out of 442 patients, 159 (36%) had low
      and 283 (64%) had normal prealbumin levels Mean age was 79.6 (73.9-84.2, p=0,405)
      years and 183 (41%, p=0,482) were males. After a median 180days of follow-up, 108
      (24%, p=0,021) patients died and 170 (38%, p=0,067) were readmitted. Mortality
      was higher in the low prealbumin group. The combined end-point was more frequent
      in the low prealbumin group (57% vs. 50%, p=0.199). In the multivariate analysis
      the following variables were associated with mortality or readmission: older age,
      exacerbated chronic HF, higher comorbidity, low systolic blood pressure and
      hemoglobin values and higher pro brain natriuretic peptide levels. CONCLUSIONS:
      Low prealbumin is common (36%) in patients with acute heart failure and it is
      associated with a higher short-term mortality.

PMID- 28499711
TI  - Does an external chest wall measurement correlate with a CT-based measurement in
      patients with chest wall deformities?
AB  - BACKGROUND: Measurements in chest wall deformities are typically conducted using
      a thorax caliper or a CT scan of the chest wall. This paper focuses on the
      possible correlation between these two methods to validate the reliability of the
      thorax caliper, minimize radiation exposure, and limit the usage of expensive
      imaging techniques. METHODS: We evaluated 95 consecutive patients (77 pectus
      excavatum (PE), 17 pectus carinatum (PC), 1 mixed deformity) who received
      surgical correction of the anterior chest wall. The results of the external chest
      wall measurements and the CT-based measurements were statistically compared.
      RESULTS: A significant correlation between the two measurements was observed in
      PE and PC at the highest point of the deformation. The strongest correlation was
      noted in PE. We also noted a correlation between the transverse diameter of the
      external measurement and the inner thoracic diameter of the CT scan but not for
      the sagittal diameters in the upper parts of the sternum. CONCLUSIONS: Thorax
      caliper measurements are suitable for determining the sagittal thoracic diameter
      at the maximum level of the deformity and the transverse diameter with an
      accuracy comparable to that of CT measurements. Since these values key, the
      thorax caliper is reliable for monitoring and documenting chest wall
      malformations. LEVEL OF EVIDENCE: Study of diagnostic test. Testing previously
      developed diagnostic criteria in a consecutive series of patients and a
      universally "gold" standard-Level I.

PMID- 28499712
TI  - Quattro Flap Tracheotomy-The impact of a novel surgical technique for young
      infants.
AB  - BACKGROUND: Tracheotomy for pediatric patients is a surgical procedure with
      greater technical difficulty and higher rates of morbidity and mortality than
      that in adults. We report a new technique for pediatric tracheotomy that reduces
      the issue of granulation and recannulation after accidental decannulation.
      METHODS: Clinical data were retrospectively reviewed for 32 pediatric patients
      aged 3weeks-32months who underwent Quattro Flap Tracheotomy (QFT) at our
      hospital. The technique for the procedure is described and illustrated in detail.
      We analyzed the complications of surgery and the prognosis of patients. RESULTS:
      Twenty-seven out of 32 pediatric tracheotomy patients were aged <12months.
      Overall, one patient with subglottic stenosis developed granulation and required
      a resection. Three patients with granulation were cured using conservative
      treatment. Neither pneumothorax nor accidental decannulation and failure to
      reinsert the cannula occurred with QFT. No tracheotomy-related deaths occurred.
      The overall rate of postoperative complications was lower in the study group
      (4/32 cases, 12.5%) than in the control group (12/32 cases, 37.5%; p=0.041).
      CONCLUSION: QFT is a new method for pediatric tracheotomy that should be
      performed in younger infants. If performed appropriately, QFT may reduce the
      incidence of complications and death in many cases that involve persistent
      granulation. LEVELS OF EVIDENCE: IV.

PMID- 28499713
TI  - Long-term outcomes of oesophageal atresia without or with proximal
      tracheooesophageal fistula - Gross types A and B.
AB  - PURPOSE: Because of an extended gap between esophageal pouches a variety of
      methods are employed to treat oesophageal atresia (OA) without (type A) or with
      (type B) proximal tracheooesophageal fistula. This retrospective observational
      study describes their single centre long-term outcomes from 1947 to 2014.
      METHODS: Of 693 patients treated for OA 68 (9.7%) had type A (n=58, 8.3%) or B
      (n=10, 1.4%). Hospital records were reviewed. Main outcome measures were survival
      and oral intake. RESULTS: Nine (13%) patients had early and 10 (15%) delayed
      primary anastomosis, 30 (44%) underwent reconstruction including colonic
      interposition (n=13), reversed gastric tube (n=11) and jejunum interposition
      (n=6), whereas19 (28%) had died without a definite repair. Median follow up was
      35 (interquartile range, 7.4-40) years. Thirty-one (63%) of 49 patients with
      definitive repair survived long term. Survival was 22% for early and 80% for
      delayed primary anastomosis, 57% for colon interposition, 82% for gastric tube
      and 84% for jejunum interposition. Gastrooesophageal reflux was most common after
      gastric tube (80%), dysphagia after colon interposition (50%), and 3 (60%) of 5
      survivors with jejunum interposition had permanent feeding ostomy because of
      neurological disorder. Endoscopic follow-up disclosed no oesophageal cancer or
      dysplasia. Repair in the most recent patients from 1985 to 2014 (n=14) included
      delayed primary anastomosis (n=7), jejunum interposition (n=6) and gastric tube
      (n=1) with 93% long-term survival. CONCLUSION: Morbidity among long-term
      survivors of type A or B OA is high. With modern management survival is, however,
      excellent and patients without neurological disorder achieve full oral intake
      either after primary anastomosis or reconstruction. LEVELS OF EVIDENCE: IV.

PMID- 28499714
TI  - Seizures in Infants Born Preterm: Defining the Scale of the Problem.

PMID- 28499716
TI  - Risk-Based Questionnaires Fail to Detect Adolescent Iron Deficiency and Anemia.
AB  - OBJECTIVE: To evaluate the predictive ability of screening questionnaires to
      identify adolescent women at high-risk for iron deficiency or iron deficiency
      anemia who warrant objective laboratory testing. STUDY DESIGN: Cross-sectional
      study of 96 female individuals 12-21 years old seen at an academic medical
      center. Participants completed an iron deficiency risk assessment questionnaire
      including the 4 Bright Futures Adolescent Previsit Questionnaire anemia
      questions, along with depression, attention, food insecurity, and daytime
      sleepiness screens. Multiple linear regression controlling for age, race, and
      hormonal contraception use compared the predictive ability of 2 models for
      adolescent iron deficiency (defined as ferritin <12 mcg/L) and anemia (hemoglobin
      <12 g/dL). Model 1, the Bright Futures questions, was compared with model 2,
      which included the 4 aforementioned screens and body mass index percentile.
      RESULTS: Among participants, 18% (17/96) had iron deficiency and 5% (5/96) had
      iron deficiency anemia. Model 1 (Bright Futures) poorly predicted ferritin and
      hemoglobin values (R2 = 0.03 and 0.08, respectively). Model 2 demonstrated
      similarly poor predictive ability (R2 = 0.05 and 0.06, respectively). Mean
      differences for depressive symptoms (0.3, 95% CI -0.2, 0.8), attention difficulty
      (-0.1, 95% CI -0.5, 0.4), food insecurity (0.04, 95% CI -0.5, 0.6), daytime
      sleepiness (0.1, 95% CI -0.1, 0.3), and body mass index percentile (-0.04, 95% CI
      -0.3, 0.2) were not significantly associated with ferritin in model 2. Mean
      differences for hemoglobin were also nonsignificant. CONCLUSIONS: Risk-based
      surveys poorly predict objective measures of iron status using ferritin and
      hemoglobin. Next steps are to establish the optimal timing for objective
      assessment of adolescent iron deficiency and anemia.

PMID- 28499717
TI  - A call to action for outpatient antibiotic stewardship.
AB  - OBJECTIVES: To address the public health threat of antibiotic resistance, there
      has been an enhanced call for antibiotic stewardship programs throughout the
      health care continuum. SUMMARY: While antibiotic stewardship programs have been
      well described in the inpatient setting, data on effectiveness and guidance on
      implementing outpatient programs is scarce. Establishing stewardship practices in
      the outpatient setting is necessary because more than 60% of human antibiotic use
      occurs in this setting. CONCLUSION: In this article, we highlight the importance
      and need for stewardship in the outpatient setting, discuss strategies for the
      development of stewardship teams, and discuss potential metrics that can be used
      to assess effectiveness of antibiotic stewardship interventions.

PMID- 28499715
TI  - Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are
      Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania.
AB  - OBJECTIVE: To assess whether growth and biomarkers of environmental enteric
      dysfunction in infancy are related to health outcomes in midchildhood in
      Tanzania. STUDY DESIGN: Children who participated in 2 randomized trials of
      micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8
      years of age). Anthropometry was measured at age 6 and 52 weeks in both trials,
      and blood samples were available from children at 6 weeks and 6 months from 1
      trial. Linear regression was used for height-for-age z-score, body mass index-for
      age z-score, and weight for age z-score, and blood pressure analyses; log
      binomial models were used to estimate risk of overweight, obesity, and stunting
      in midchildhood. RESULTS: One hundred thirteen children were followed-up. Length
      for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks
      were associated independently and positively with height-for-age z-score and
      inversely associated with stunting in midchildhood. Delta weight-for-length and
      weight-for-age z-score were also positively associated with midchildhood height
      for-age z-score. The 6-week and delta weight-for-length z-scores were associated
      independently and positively with midchildhood body mass index-for-age z-score
      and overweight, as was the 6-week and delta weight-for-age z-score. Delta length
      for-age z-score was also associated with an increased risk of overweight in
      midchildhood. Body mass index-for-age z-score in midchildhood was associated
      positively with systolic blood pressure. Serum anti-flagellin IgA concentration
      at 6 weeks was also associated with increased blood pressure in midchildhood.
      CONCLUSIONS: Anthropometry at 6 weeks and growth in infancy independently predict
      size in midchildhood, while anti-flagellin IgA, a biomarker of environmental
      enteric dysfunction, in early infancy is associated with increased blood pressure
      in midchildhood. Interventions in early life should focus on optimizing linear
      growth while minimizing excess weight gain and environmental enteric dysfunction.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.

PMID- 28499718
TI  - Family amyloid polyneuropathy, sympathetic denervation and liver transplantation.

PMID- 28499719
TI  - Diabetes, hypoxia and cardiovascular disease: From molecular mechanism to
      treatment.

PMID- 28499720
TI  - T follicular helper and TH2 cells in allergic responses.
AB  - IL-4 is a cytokine commonly secreted by TH2 and follicular helper T (TFH) cells
      after antigenic sensitization. TH2 cells have been thought to be the major
      contributor of B cell help as a source of IL-4 responsible for class switch
      recombination to Immunoglobulin G1 (IgG1) and Immunoglobulin E (IgE).
      Importantly, there are some differences in transcriptional regulation between
      these two T cell subsets. The IL-4 production by TH2 and TFH cells is
      distinctively regulated by two pathways, GATA-3-mediated Il4-HS2 enhancer and
      Notch mediated Il4-CNS-2 enhancer. IgE and IgG1 antibody responses are mainly
      controlled by IL-4-secreting TFH cells, but not by TH2 cells. In this review, we
      discuss the role of TH2 and TFH cells in IgE production and allergic responses.

PMID- 28499721
TI  - Efficacy of South African Babesia bovis vaccine against field isolates.
AB  - A high-passage Babesia bovis vaccine containing only one genotype population was,
      although protective, inferior compared to the immunity afforded by a lower
      passage of the same strain containing two populations. The 24 times serially
      passaged South African B. bovis S vaccine strain contain only a single parasite
      population (Bv80 allele A 558bp). Forty-four field isolates sampled were all
      found different with regard to the number and composition of the parasite
      populations present in each isolate. The extensive genotypic diversity in South
      Africa and the limited genotypic diversity observed in the S24 vaccine, raised
      the question on its ability to protect against such diverse populations. The 6
      isolates selected for challenge in the current study originated from
      geographically distinct populations that also possessed thirteen unique genotypes
      based on the Bv80 gene and included strains that resulted in clinical disease.
      The strain coverage was therefore much greater than in previous studies on the
      protective ability of the S24 vaccine. Challenge of vaccinated cattle indicated
      that the vaccine gave adequate protection against 5/6 isolates. Protection
      against the remaining isolate proved inadequate. However, field observations in
      the region where this isolate originated from, showed only minor mortalities in
      vaccinated animals compared to losses experienced in unvaccinated herds. This
      study demonstrated the ability of the South African B. bovis S24 vaccine to
      protect cattle against challenge from local field isolates containing single or
      multiple parasite populations.

PMID- 28499722
TI  - Babesia genotypes in Haemaphysalis concinna collected from birds in Hungary
      reflect phylogeographic connections with Siberia and the Far East.
AB  - Haemaphysalis concinna is the second most common tick species attaching to birds
      in Hungary. Recently, Babesia genotypes, found in Siberia and the Far East, have
      been detected in this tick species collected from the vegetation in Hungary and
      Slovakia. The aim of this study was to molecularly investigate if these
      piroplasms also occur in H. concinna carried by migratory birds, which might
      explain their occurrence in the western Palaearctic. During a 2-year period, 321
      H. concinna larvae and nymphs were collected from 121 passerine birds (of 19
      species) in Hungary. These were molecularly investigated for the presence of
      piroplasm DNA with PCR and sequencing. The prevalence of PCR positive ticks was
      15.9% (51 out of 321). Piroplasm PCR positivity of H. concinna ticks was
      significantly more frequent during the summer and autumn compared to spring,
      suggesting that migratory birds arriving in Hungary from the north or north east
      are the most important in the dispersal of H. concinna-associated piroplasms.
      Three genotypes, i.e. Babesia sp. "Irk-Hc133", "Irk-Hc130" (originally found in
      Irkutsk, Siberia) and "Kh-Hc222" (originally found in Khabarovsk, Far East) were
      detected. Phylogenetically all these belonged to the group formed by Babesia spp.
      of ruminants. Four bird species, which had 14-60% prevalence of PCR positive
      ticks, are known to be associated with northeast to southwest autumn migration.
      In conclusion, the presence of Central and East Asian Babesia genotypes in
      Central Europe are most likely related to bird species with known eastern
      migratory habit and/or phylogenetically substantiated connections between their
      eastern and western Eurasian populations.

PMID- 28499723
TI  - A dual-site gateway cloning system for simultaneous cloning of two genes for
      plant transformation.
AB  - Analyses of the subcellular localization of proteins and protein-protein
      interaction networks are essential to uncover the molecular basis of diverse
      biological processes in plants. To this end, we have created a Gateway cloning
      compatible vector system, named dual-site (DS) Gateway cloning system to allow
      simple cloning of two expression cassettes in a binary vector and to express them
      simultaneously in plant cells. In the DS Gateway cloning system, (i) a moderate
      constitutive nopaline synthase promoter (Pnos), which is much suitable for
      localization analysis, is used to guide each expression cassette, (ii) four
      series of vectors with different plant resistance markers are established, (iii)
      N-terminal fusion with 6 fluorescent proteins and 7 epitope tags is available,
      (iv) both N- and C-terminal fusions with split enhanced yellow fluorescent
      protein (EYFP) are possible for efficient detection of protein-protein
      interactions using a bimolecular fluorescence complementation (BiFC) assay. The
      usefulness of the DS Gateway cloning system has been demonstrated by the analysis
      of the expression and the subcellular localization patterns of two Golgi proteins
      in stable expression system using A. thaliana, and by the analyses of
      interactions between subunits of coat protein complex II (COPII) both in
      transient and stable expression systems using Japanese leek and A. thaliana,
      respectively. The DS Gateway cloning system provides a multipurpose, efficient
      expression tool in gene function analyses and especially suitable for
      investigating interactions and subcellular localization of two proteins in living
      plant cells.

PMID- 28499725
TI  - Antibiotic prescribing and resistance: knowledge among Latin American medical
      students during Antibiotic Awareness Week 2016.

PMID- 28499724
TI  - Cardio-oncology in the older adult.
AB  - Heart disease and cancer are the leading causes of death in older adults. Many
      first-line cancer treatments have the potential for cardiotoxicity. Age-related
      risk factors, pre-existing cardiac disease, and a high prevalence of
      comorbidities are reasons for increased cardiotoxicity in older adults. Concerns
      regarding cardiotoxicity may lead to frailty bias and undertreatment, resulting
      in suboptimal outcomes. There is an urgent need for geriatric-specific evidence
      and guidelines to help tailor care for this vulnerable group. A multi
      disciplinary approach based on close collaboration between oncologists,
      cardiologists, and geriatricians, among other specialist clinicians is essential.

PMID- 28499726
TI  - Inhibitory effect of donepezil on bradykinin-induced increase in the
      intracellular calcium concentration in cultured cortical astrocytes.
AB  - Donepezil is a potent and selective acetylcholinesterase inhibitor developed for
      the treatment of Alzheimer's disease. In the present study, we investigated the
      responses of astrocytes to bradykinin, an inflammatory mediator, and the effect
      of donepezil on these responses using cultured cortical astrocytes. Bradykinin
      induced a transient increase of intracellular calcium concentration ([Ca2+]i) in
      cultured astrocytes. Bradykinin-induced [Ca2+]i increase was inhibited by the
      exposure to thapsigargin, which depletes Ca2+ stores on endoplasmic reticulum,
      but not by the exclusion of extracellular Ca2+. Twenty four hours pretreatment of
      donepezil reduced the bradykinin-induced [Ca2+]i increase. This reduction was
      inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt
      inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the
      intracellular reactive oxygen species level in astrocytes. These results suggest
      that donepezil inhibits the inflammatory response induced by bradykinin via nAChR
      and PI3K-Akt pathway in astrocytes.

PMID- 28499727
TI  - The Rush from Judgment.

PMID- 28499729
TI  - Doubts about dementia diagnoses.

PMID- 28499728
TI  - Push-Alert Notification of Troponin Results to Physician Smartphones Reduces the
      Time to Discharge Emergency Department Patients: A Randomized Controlled Trial.
AB  - STUDY OBJECTIVE: For emergency department (ED) patients with chest pain,
      discharge decisions often hinge on troponin results. Push-alert notifications
      deliver results immediately to physician smartphones. Our objective is to
      determine whether troponin push alerts improve the time to discharge decisions
      for ED patients with chest pain. METHODS: In an academic ED, we assessed the
      effect of a quality improvement initiative using troponin push alerts to
      physician smartphones, with a cluster-randomized evaluation. Participating
      physicians were randomized to receive troponin push alerts (intervention) or not
      receive them (control). We retrospectively identified patients treated by
      participating physicians during the study period who were discharged from the ED
      with chest pain. The primary outcome was the time from final troponin result to
      discharge decision. Secondary outcomes included length of stay. A linear mixed
      model was used to adjust for physician clustering. RESULTS: During the study,
      1,554 patients were discharged from the ED with chest pain. There were 551
      patients in the control group and 554 in the intervention group who met inclusion
      criteria. The overall median interval from final troponin result to discharge
      decision was 79.7 minutes (interquartile range [IQR] 33.6 to 167.8 minutes); it
      was 94.3 minutes (IQR 36.2 to 177.8 minutes) in the control group and 68.5
      minutes (IQR 30.5 to 157.2 minutes) in the intervention group. This 25.8-minute
      difference in medians (95% confidence interval 24.6 to 28.0 minutes) was
      statistically significant. Total ED length of stay was 345 minutes (IQR 261 to
      419 minutes) in the control group and 328 minutes (IQR 250 to 408 minutes) in the
      intervention group. CONCLUSION: Physicians who received troponin push alerts
      discharged their patients with chest pain 26 minutes faster than those without
      troponin notifications. Total ED length of stay did not significantly improve for
      these patients.

PMID- 28499730
TI  - Effects of Withdrawing alpha1-Blocker from Combination Therapy with alpha1
      Blocker and 5alpha-Reductase Inhibitor in Patients with Lower Urinary Tract
      Symptoms Suggestive of Benign Prostatic Hyperplasia: A Prospective and
      Comparative Trial Using Urodynamics.
AB  - PURPOSE: We compared the effects on lower urinary tract symptoms and bladder
      outlet obstruction of combination therapy with alpha1-blocker and 5alpha
      reductase inhibitor or a switch to 5alpha-reductase inhibitor monotherapy. We
      determined the factors influencing changes in lower urinary tract symptoms after
      alpha1-blocker withdrawal. MATERIALS AND METHODS: A total of 140 outpatients with
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia received
      combination therapy with silodosin 8 mg per day and dutasteride 0.5 mg per day
      for 12 months. Of the patients 132 were randomized to continue combination
      therapy or switched to dutasteride monotherapy through silodosin withdrawal as
      the monotherapy group. Parameter changes from before randomization to 12 months
      after randomization were assessed based on subjective symptoms and urodynamic
      findings of voiding and storage function. RESULTS: Efficacy analysis included 57
      patients on combination therapy and 60 on monotherapy. The change in I-PSS
      (International Prostate Symptom Score) after randomization was -0.7 and -0.6 in
      the combination therapy and monotherapy groups, respectively. The bladder outlet
      obstruction index changed from 46.1 to 41.8 in the combination therapy group and
      from 42.9 to 39.9 in the monotherapy group. No significant differences in
      subjective symptoms and bladder outlet obstruction were observed between the 2
      groups. However, storage function decreased in the monotherapy group and lower
      urinary tract symptoms deteriorated significantly after the switch to dutasteride
      monotherapy in patients with a higher body mass index. CONCLUSIONS: We found that
      alpha1-blocker withdrawal from combination therapy was reasonable and tolerable
      with regard to the effect on lower urinary tract symptoms and bladder outlet
      obstruction. However, withdrawal must be performed carefully in patients with a
      high body mass index.

PMID- 28499731
TI  - Discovery of N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and 
      phenyl carboxamide series of MU-opioid receptor antagonists.
AB  - Gastrointestinal dysfunction as a consequence of the use of opioid analgesics is
      of significant clinical concern. First generation drugs to treat these opioid
      induced side-effects were limited by their negative impact on opioid receptor
      agonist-induced analgesia. Second generation therapies target a localized,
      peripherally-restricted, non-CNS penetrant drug distribution of opioid receptor
      antagonists. Herein we describe the discovery of the N-substituted-endo-3-(8-aza
      bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of MU-opioid
      receptor antagonists. This report highlights the discovery of the key MU-opioid
      receptor antagonist pharmacophore and the optimization of in vitro metabolic
      stability through the application of a phenol bioisostere. The compounds 27a and
      31a with the most attractive in vitro profile, formed the basis for the
      application of Theravance Biopharma's multivalent approach to drug discovery to
      afford the clinical compound axelopran (TD-1211), targeted for the treatment of
      opioid-induced constipation.

PMID- 28499732
TI  - Activity of resveratrol triesters against primary acute lymphoblastic leukemia
      cells.
AB  - Resveratrol is a common polyphenol of plant origin known for its cancer
      prevention and other properties. Its wider application is limited due to poor
      water solubility, low stability, and weak bioavailability. To overcome these
      limitations, a series of 13 novel resveratrol triesters were synthesized
      previously. In this paper, we describe the synthesis of 3 additional derivatives
      and the activity of all 16 against primary acute lymphoblastic leukemia cells. Of
      these, 3 compounds were more potent than resveratrol (IC50=10.5uM) namely:
      resveratryl triacetate (IC50=3.4uM), resveratryl triisobutyrate (IC50=5.1uM), and
      resveratryl triisovalerate (IC50=4.9uM); all other derivatives had IC50 values of
      >10uM. Further studies indicated that the active compounds caused G1 phase
      arrest, increased expression of p53, and induced characteristics of apoptotic
      cell death. Moreover, the compounds were only effective in cycling cells, with
      cells arrested in G1 phase being refractory.

PMID- 28499733
TI  - Alkaloids from aerial parts of Houttuynia cordata and their anti-inflammatory
      activity.
AB  - New alkaloids, houttuynamide B and C (1, 2) and houttuycorine (14), were isolated
      from the aerial parts of Houttuynia cordata Thunb. in addition to eighteen known
      alkaloids. Their structures were elucidated through extensive spectroscopic
      analysis. All the isolates were tested for their inhibitory activity against NO
      production in RAW 264.7 cells stimulated by LPS. Of the tested compounds,
      compound 15 showed the most potent anti-inflammatory activity with an IC50 value
      of 8.7MUM.

PMID- 28499734
TI  - Preoperative controlling nutritional status (CONUT) score as a novel predictive
      biomarker of survival in patients with localized urothelial carcinoma of the
      upper urinary tract treated with radical nephroureterectomy.
AB  - OBJECTIVE: The purpose of this study was to investigate the correlation between
      the controlling nutritional status (CONUT) score and survival of patients with
      localized urothelial carcinoma of the upper urinary tract treated with radical
      nephroureterectomy (RNU). METHODS AND MATERIALS: We retrospectively enrolled 107
      patients. CONUT score was calculated based on the serum albumin concentration,
      lymphocyte count, and total cholesterol concentration. Patients were classified
      into 2 groups based on CONUT score. Relapse-free survival (RFS), cancer-specific
      survival (CSS), and overall survival (OS) after RNU were compared between the 2
      groups, and predictors of survival were analyzed using Cox proportional hazards
      regression models. RESULTS: For CONUT score, the area under the curve was 0.588
      and the optimal cutoff value was 3. Twenty-four patients (22.4%) had high CONUT
      scores. The patients with high CONUT scores had significantly shorter 5-year RFS,
      CSS, and OS than did those with low CONUT scores (RFS: 50.1% vs. 66.0%; CSS:
      28.1% vs. 71.7%; OS: 26.4% vs. 66.8%; all P<0.05). Results of the multivariable
      analysis, after adjustment for factors such as pT stage, pN stage, tumor grade,
      presence of lymphovascular invasion, and C-reactive protein level, revealed that
      CONUT score was an independent predictor of CSS (hazard ratio [HR] = 5.44, P =
      0.0016) and OS (HR = 2.90, P = 0.0214) and showed marginal significance for
      predicting RFS (HR = 2.26, P = 0.0581). CONCLUSIONS: Preoperative CONUT score
      helps predict survival in patients with localized urothelial carcinoma of the
      upper urinary tract treated with RNU.

PMID- 28499735
TI  - Turkish Standardized Reading Passage for the Evaluation of Hard Glottal Attack
      Occurrence Frequency.
AB  - OBJECTIVE: This study aimed to develop a Turkish reading passage that can be used
      in evaluating the frequency of hard glottal attack (HGA) and to assess its
      reliability. STUDY DESIGN: This is a prospective case-control study. METHODS: The
      Towne-Heuer reading passage is a valuable tool that can be used for the auditory
      perceptual assessment of voice. The characteristics of the first four paragraphs
      of the reading passage were analyzed by a linguist. Then, a Turkish reading
      passage with similar characteristics was developed. The control group (n = 21)
      consisted of individuals with no voice disorder. The study group consisted of two
      subgroups that were diagnosed as having vocal fold nodules (n = 11) and muscle
      tension dysphonia (n = 10). A total of three listeners were evaluated for the
      frequency of HGAs. One of the listeners was a master's student, whereas the other
      two listeners were speech-language pathologists. Consistency between the
      listeners was evaluated by using the percent agreement and the kappa statistics.
      Intrarater reliability was assessed by the Wilcoxon sign test. The t test was
      used to evaluate potential differences between the groups. The results were
      considered as significant if the P value was <0.05. RESULTS: The average attack
      number in the study group was found to be significantly higher than the controls
      (P < 0.05). No significant difference could be discerned between the muscle
      tension dysphonia and vocal nodule subgroups (P > 0.05). CONCLUSIONS: Findings
      confirmed that HGAs are clearly related to the vocal hyperfunction; however, the
      mechanism of action needs more research. In addition, the relationship between
      syllable stress and HGA should be further researched to clarify the cause of the
      attack number differences between English and Turkish languages.

PMID- 28499736
TI  - [Children's medically complex diseases unit. A model required in all our
      hospitals].
AB  - INTRODUCTION: The increase in survival of children with severe diseases has led
      to the rise of children with chronic diseases, sometimes with lifelong
      disabilities. In 2008, a unit for the specific care of medically complex children
      (MCC) was created in Hospital La Paz. OBJECTIVES: To describe the work and care
      activities of this Unit. Patients and methods An analysis was performed on all
      discharge reports of the Unit between January 2014 and July 2016. RESULTS: The
      MCC Unit has 6 beds and daily outpatient clinic. A total of 1,027 patients have
      been treated since the creation of the unit, with 243 from 2014. The median age
      was 24.2 months (IQ: 10.21-84.25). The large majority (92.59%) have multiple
      diseases, the most frequent chronic conditions observed were neurological
      (76.95%), gastrointestinal (63.78%), and respiratory diseases (61.72%). More than
      two-thirds (69.54%) of MCC are dependent on technology, 53.49% on respiratory
      support, and 35.80% on nutritional support. Hospital admission rates have
      increased annually. There have been 403 admissions since 2014, of which 8.93%
      were re-admissions within 30 days of hospital discharge. The median stay during
      2014-2016 was 6 days (IQ: 3-14). The occupancy rate has been above 100% for this
      period. Currently, 210 patients remain on follow-up (86.42%), and 11 children
      (4.53%) were discharged to their referral hospitals. The mortality rate is 9.05%
      (22 deaths). The main condition of these 22 patients was neurological (9
      patients). Infectious diseases were the leading cause of death. CONCLUSION: MCC
      should be treated in specialized units in tertiary or high-level hospitals.

PMID- 28499737
TI  - Endovascular Repair as a Bridge to Open Repair of a Ruptured Descending Thoracic
      Aspergillus Aortitis.
AB  - Invasive aspergillosis rarely involves the thoracic aorta and is associated with
      a poor prognosis. A 56-year-old heart transplant recipient presented with
      invasive aspergillosis, primary Aspergillus aortitis, and a ruptured thoracic
      aorta pseudoaneurysm. Open surgical repair was not possible because of severe
      sepsis. Therefore, a sequential surgical strategy was planned, including
      emergency thoracic endovascular aortic repair, followed by antifungal treatment
      and definitive open repair with explantation of the endograft and placement of a
      cryopreserved arterial allograft under extracorporeal membrane oxygenator
      support. The infection did not reoccur during follow-up, and the patient remained
      alive and well 13 months after the operation.

PMID- 28499738
TI  - Cognitive effects of subdiaphragmatic vagal deafferentation in rats.
AB  - Vagal afferents are a crucial neuronal component of the gut-brain axis and
      mediate the information flow from the viscera to the central nervous system.
      Based on the findings provided by experiments involving vagus nerve stimulation,
      it has been suggested that vagal afferent signaling may influence various
      cognitive functions such as recognition memory and cognitive flexibility. Here,
      we examined this hypothesis using a rat model of subdiaphragmatic vagal
      deafferentation (SDA), the most complete and selective abdominal vagal
      deafferentation method existing to date. We found that SDA did not affect working
      memory in a nonspatial alternation task, nor did it influence short-,
      intermediate-, and long-term object recognition memory. SDA did also not affect
      the acquisition of positively reinforced left-right discrimination learning, but
      it facilitated the subsequent reversal left-right discrimination learning. The
      SDA-induced effects on reversal learning emerged in the absence of concomitant
      changes in motivation towards the positive reinforcer, indicating selective
      effects on cognitive flexibility. Taken together, these findings suggest that the
      relative contribution of vagal afferent signaling to cognitive functions is
      limited. At the same time, our study demonstrates that cognitive flexibility, at
      least in the domains of positively reinforced learning, is subjected to visceral
      modulation through abdominal vagal afferents.

PMID- 28499739
TI  - Diatom communities on commercial biocidal fouling control coatings after one year
      of immersion in the marine environment.
AB  - Little is known about the effect of commercial biocidal fouling control coatings
      on fouling diatom communities and their growth forms after long periods of
      exposure in the marine tropical environment. The current study investigated the
      abundance and composition of fouling diatom communities developed on 11
      commercially available biocidal antifouling coatings, covering the three main
      technology types in recent historic use (Self-Polishing Copolymers, Self
      Polishing Hybrid and Controlled Depletion Polymers) after one year of static
      immersion at two locations in Muscat, Oman (Marina Shangri La and Marina Bandar
      Rowdha). Light microscopy demonstrated that the total abundance of diatoms and
      the relative abundance of growth forms were significantly affected by the choice
      of biocidal antifouling coating and experimental location. Using scanning
      electron microscopy, a total of 21 diatom genera were identified which were
      grouped into adnate, motile, plocon and erect growth forms. The adnate growth
      forms, mainly the genera Amphora, Cocconeis and Mastogloia, dominated the other
      growth forms in terms of their relative abundance. Current results revealed the
      importance of exposure location and choice of biocidal antifouling coating on the
      relative abundance of diatom growth forms.

PMID- 28499740
TI  - Metastability in Senescence.
AB  - The brain during healthy aging exhibits gradual deterioration of structure but
      maintains a high level of cognitive ability. These structural changes are often
      accompanied by reorganization of functional brain networks. Existing
      neurocognitive theories of aging have argued that such changes are either
      beneficial or detrimental. Despite numerous empirical investigations, the field
      lacks a coherent account of the dynamic processes that occur over our lifespan.
      Taking advantage of the recent developments in whole-brain computational modeling
      approaches, we hypothesize that the continuous process of aging can be explained
      by the concepts of metastability - a theoretical framework that gives a
      systematic account of the variability of the brain. This hypothesis can bridge
      the gap between existing theories and the empirical findings on age-related
      changes.

PMID- 28499742
TI  - Understanding constraints on sport performance from the complexity sciences
      paradigm: An ecological dynamics framework.
AB  - Glazier's suggestion for the constraints-led approach as a GUT for sport
      performance is a worthy proposal. What is missing from these preliminary insights
      is a principled basis, in the form of pillars, for understanding the cornerstones
      of the sports medicine profession, and this lack of an overarching theoretical
      framework is also somewhat of a limitation in Glazier's initial ideas, as we
      argue later. Here we suggest that his preliminary proposal would benefit from
      considering a more comprehensive ontological positioning within the complexity
      sciences paradigm to benefit from conceptualising athletes and sports teams as
      complex adaptive systems. We argue that ecological dynamics provides a more
      encompassing rationale than the constraint-led approach because it is a multi
      dimensional theoretical framework shaped by many relevant disciplines.

PMID- 28499741
TI  - The Origins of Social Categorization.
AB  - Forming conceptually-rich social categories helps people to navigate the complex
      social world by allowing them to reason about the likely thoughts, beliefs,
      actions, and interactions of others, as guided by group membership. Nevertheless,
      social categorization often has nefarious consequences. We suggest that the
      foundation of the human ability to form useful social categories is in place in
      infancy: social categories guide the inferences infants make about the shared
      characteristics and social relationships of other people. We also suggest that
      the ability to form abstract social categories may be separable from the eventual
      negative downstream consequences of social categorization, including prejudice,
      discrimination, and stereotyping. Although a tendency to form inductively-rich
      social categories appears early in ontogeny, prejudice based on each particular
      category dimension may not be inevitable.

PMID- 28499743
TI  - Resolution of the uncertainty in the kinetic mechanism for the trans-3
      Chloroacrylic acid dehalogenase-catalyzed reaction.
AB  - trans- and cis-3-Chloroacrylic acid dehalogenase (CaaD and cis-CaaD,
      respectively) catalyze the hydrolytic dehalogenation of their respective isomers
      and represent key steps in the bacterial conversion of 1,3-dichloropropene to
      acetaldehyde. In prior work, a kinetic mechanism for the CaaD-catalyzed reaction
      could not be unequivocally determined because (1) the order of product release
      could not be determined and (2) the fluorescence factor for the enzyme species,
      E*PQ (where P = bromide and Q = malonate semialdehyde, the two products of the
      reaction) could not be assigned. The ambiguities in the model have now been
      resolved by stopped-flow experiments following the reaction using an active site
      fluorescent probe, alphaY60W-CaaD and 3-bromopropiolate, previously shown to be a
      mechanism-based inhibitor of CaaD, coupled with the rate of bromide release in
      the course of CaaD inactivation. A global fit of the combined datasets provides a
      complete minimal model for the reaction of alphaY60W-CaaD and 3-bromoacrylate. In
      addition, the global fit produces kinetic constants for CaaD inactivation by 3
      bromopropiolate and implicates the acyl bromide as the inactivating species.
      Finally, a comparison of the model with that for cis-CaaD shows that for both
      enzymes turnover is limited by product release and not chemistry.

PMID- 28499744
TI  - Does prednisone use or disease activity in pregnant women with rheumatoid
      arthritis influence the body composition of their offspring?
AB  - Glucocorticoids are given during pregnancy when rheumatoid arthritis (RA) is too
      active. It could lead to increased risk of cardiovascular diseases (CVD) and type
      2 diabetes mellitus (T2DM) in the offspring. Elevated RA disease activity during
      pregnancy is associated with low birth weight and rapid post-natal growth. Both
      can negatively influence the body composition later in life. This study shows
      that prednisone use or RA disease activity in pregnant women with RA had no
      influence on the body composition of prepubertal offspring. Furthermore, no
      components of the metabolic syndrome (MetS) were present in the children, which
      minimalize the change on CVD or T2DM later in life. This reassuring conclusion
      might lead to a different therapeutic view when glucocorticoid treatment during
      pregnancy is inevitable.

PMID- 28499745
TI  - Distress in Caregivers Accompanying Patients to an Emergency Department: A
      Scoping Review.
AB  - BACKGROUND: Despite substantial research interest in caregiver distress in the
      emergency department (ED), no recent review of the literature exists. OBJECTIVE:
      Our aims were to map primary research on caregiver distress in the ED, synthesize
      key concepts underpinning the literature, identify gaps, and provide guidance for
      future work. METHODS: We used a five-stage scoping review with tandem screening
      and data extraction. RESULTS: Of 2121 records, 29 studies were included. The
      majority were small, conducted in North America or Europe, and published after
      2000. Numerous methodologies and definitions of distress were represented. The
      majority involved children, with just five studies restricted to adults. Many
      involved higher-acuity scenarios, such as resuscitations or invasive procedures.
      The most common research topic was anxiety of parents of children undergoing
      procedures. Effects of witnessed resuscitation were also addressed. Parental
      presence may reduce anxiety during venipuncture, while only waiting room music
      reduced anxiety in parents of children not undergoing a procedure. No study
      explored interventions to reduce distress in caregivers of adults. While
      heterogeneity precluded evidence-based recommendations, clinically relevant
      observations emerged, including that anxiety can be worsened if a caregiver
      believes their patient has been forgotten; that parents are sensitive about being
      perceived as neglectful; and that sympathy and confidence ease distress, as does
      sensitivity toward end-of-life issues. Several studies suggested that negative
      staff behaviors affect caregiver anxiety. CONCLUSIONS: Future studies should use
      validated measures of distress; include larger samples; and capture adult,
      geriatric, and rural populations. A focused systematic review might yield
      evidence-based guidance for clinicians.

PMID- 28499746
TI  - Comparing Access to Laser Capsulotomy Performed by Optometrists and
      Ophthalmologists in Oklahoma by Calculated Driving Distance and Time.
AB  - PURPOSE: To quantify Medicare beneficiary proximity to his or her yttrium
      aluminum-garnet (YAG) laser capsulotomy-providing ophthalmologist and optometrist
      in Oklahoma by calculating driving distances and times. DESIGN: Cross-sectional
      cohort study using 2014 Oklahoma Medicare 100% and 5% data sets and Google Maps
      distance and travel time application programming interfaces. PARTICIPANTS: U.S.
      fee-for-service Medicare beneficiaries and Oklahoma ophthalmologist and
      optometrist laser capsulotomy providers. METHODS: The 2014 Medicare Provider
      Utilization and Payment Limited 100% and 5% datasets from the Centers for
      Medicare and Medicaid (CMS) were obtained to identify the office street addresses
      of Oklahoma ophthalmologists and optometrists who submitted claims to Medicare
      for a YAG laser capsulotomy, and the county addresses of the corresponding
      Medicare beneficiaries who received the laser capsulotomy. The shortest travel
      distances and travel times between the beneficiary and the laser provider were
      calculated by using Google Maps distance and travel time application programming
      interfaces. MAIN OUTCOME MEASURES: Beneficiary driving distances and times to his
      or her YAG laser capsulotomy-providing Oklahoma ophthalmologist and optometrist.
      RESULTS: In 2014, 90 (57%) of 157 Oklahoma ophthalmologists and 65 (13%) of 506
      Oklahoma optometrists submitted a total of 7521 and 3751 YAG laser capsulotomy
      claims to Medicare, respectively. By using the Medicare Limited 5% dataset, there
      was no difference in driving distance between beneficiaries who received a laser
      capsulotomy from an ophthalmologist (median, 39 miles; interquartile range [IQR],
      13-113 miles) compared with an optometrist (median, 46 miles; IQR, 13-125 miles;
      P = 0.93) or in driving time to an ophthalmologist (median, 47 minutes; IQR, 19
      110 minutes) compared with an optometrist (median, 50 minutes; IQR, 17-117
      minutes; P = 0.76). CONCLUSIONS: For Medicare beneficiaries, there was no
      difference in geographic access to YAG laser capsulotomy whether performed by an
      Oklahoma ophthalmologist or optometrist as determined by calculated driving
      distances and times.

PMID- 28499747
TI  - Preoperative Posturing of Patients with Macula-On Retinal Detachment Reduces
      Progression Toward the Fovea.
AB  - PURPOSE: Traditionally, preoperative posturing consisting of bed rest and
      positioning is prescribed to patients with macula-on retinal detachment (RD) to
      prevent RD progression and detachment of the fovea. Execution of such advice can
      be cumbersome and expensive. This study aimed to investigate if preoperative
      posturing affects the progression of RD. DESIGN: Prospective cohort study.
      PARTICIPANTS: Ninety-eight patients with macula-on RD were included. Inclusion
      criteria were volume optical coherence tomography (OCT) scans could be obtained
      with sufficient quality; and the smallest distance from the fovea to the
      detachment border was 1.25 mm or more. METHODS: Patients were admitted to the
      ward for bed rest in anticipation of surgery and were positioned on the side
      where the RD was mainly located. At baseline and before and after each
      interruption for meals or toilet visits, a 37 degrees *45 degrees  OCT volume
      scan was performed using a wide-angle Spectralis OCT (Heidelberg Engineering,
      Heidelberg, Germany). The distance between the nearest point of the RD border and
      fovea was measured using a custom-built measuring tool. MAIN OUTCOME MEASURES:
      The RD border displacement and the average RD border displacement velocity moving
      toward (negative) or away (positive) from the fovea were determined for intervals
      of posturing and interruptions. RESULTS: The median duration of intervals of
      posturing was 3.0 hours (interquartile range [IQR], 1.8-14.0 hours; n = 202) and
      of interruptions 0.37 hours (IQR, 0.26-0.50 hours; n = 197). The median RD border
      displacement was 2 MUm (IQR, -65 to +251 MUm) during posturing and -61 MUm (IQR, 
      140 to 0 MUm) during interruptions, a statistically significant difference (P <
      0.001, Mann-Whitney U test). The median RD border displacement velocity was +1
      MUm/hour (IQR, -21 to +49 MUm/hour) during posturing and -149 MUm/hour (IQR, -406
      to +1 MUm/hour) during interruptions, a statistically significant difference (P <
      0.001). CONCLUSIONS: By making use of usual interruptions of preoperative
      posturing we were able to show, in a prospective and ethically acceptable manner,
      that RD stabilizes during posturing and progresses during interruptions in
      patients with macula-on RD. Preoperative posturing is effective in reducing
      progression of RD.

PMID- 28499748
TI  - Rates of Local Retinal Nerve Fiber Layer Thinning before and after Disc
      Hemorrhage in Glaucoma.
AB  - PURPOSE: To investigate longitudinal temporal and spatial associations between
      disc hemorrhage (DH) and rates of local retinal nerve fiber layer (RNFL) thinning
      before and after DHs. DESIGN: Longitudinal, observational cohort study.
      PARTICIPANTS: Forty eyes of 37 participants (23 with glaucoma and 17 with suspect
      glaucoma at baseline) with DH episodes during follow-up from the Diagnostic
      Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation
      Study. METHODS: All subjects underwent optic disc photography annually and
      spectral-domain optical coherence tomography (OCT) RNFL thickness measurements
      every 6 months. The rates of RNFL thinning were calculated using multivariate
      linear mixed-effects models before and after DH. MAIN OUTCOME MEASURES: Rates of
      global and local RNFL thinning. RESULTS: Thirty-six eyes of 33 participants with
      inferior or superior DHs were analyzed. The rates of RNFL thinning were
      significantly faster in DH quadrants than in non-DH quadrants after DH (-2.25 and
      -0.69 MUm/year; P < 0.001). In the 18 eyes with intensified treatment after DH,
      the mean rate of RNFL thinning significantly slowed after treatment compared with
      before treatment in the non-DH quadrants (-2.89 and -0.31 MUm/year; P < 0.001),
      but not in the DH quadrants (-2.64 and -2.12 MUm/year; P = 0.19). In 18 eyes with
      unchanged treatment, the rate of RNFL thinning in the DH quadrant was faster
      after DH than before DH (P = 0.008). Moreover, compared with eyes without a
      treatment change, intensification of glaucoma treatment after DH significantly
      reduced the global, non-DH quadrants, and DH quadrant rates of RNFL thinning
      after DH compared with before DH (global, P = 0.004; non-DH quadrant, P < 0.001;
      DH quadrant, P = 0.005). In the multiple linear regression analysis, treatment
      intensification (beta, 1.007; P = 0.005), visual field mean deviation (beta,
      0.066; P = 0.049), and difference in intraocular pressure before and after DH
      (beta, -0.176; P = 0.034) were associated significantly with the difference of
      global RNFL slope values before and after DH. CONCLUSIONS: Although the rate of
      RNFL thinning worsened in a DH quadrant after DH, glaucoma treatment
      intensification may have a beneficial effect in reducing this rate of thinning.

PMID- 28499749
TI  - A double blinded prospective randomized trial comparing the effect of anatomic
      versus non-anatomic resection on hepatocellular carcinoma recurrence.
AB  - BACKGROUND: The aim of this study was to determine the effect of anatomic
      resection (AR) versus non-anatomic resection (NAR) on recurrence rates in
      patients with hepatocellular carcinoma (HCC). METHODS: Eligible patients were
      randomized to AR or NAR from January 2006 to July 2007 at a single center. The
      primary outcome was the 2-year recurrence-free survival (RFS). Secondary outcomes
      were postoperative complications, time to first recurrence, 1-, 3-, and 5-year
      RFS, and overall survival (OS). RESULTS: Fifty-three (51%) and 52 (50%) patients
      underwent NAR and AR, respectively. A larger proportion of patients achieved
      margins >=20 mm in the AR group (52% vs. 30%; P = 0.023). Complications (blood
      loss, transfusion requirement, and hospital stay) were similar between the two
      groups. Median follow-up was 33 (range, 2-77) months. Incidence of local
      recurrence at 2 years was 30% and 59% in the AR and NAR groups, respectively.
      Median time to first local recurrence in the AR group was significantly longer
      than in the NAR group (53 vs. 10 months, P = 0.010). There was no difference in
      overall RFS between the two groups (P = 0.290). DISCUSSION: AR decreased the 2
      year local recurrence rate and increased the time to first local recurrence
      compared to NAR in patients with HCC.

PMID- 28499750
TI  - Ticket to Ride: Targeting Proteins to Exosomes for Brain Delivery.

PMID- 28499751
TI  - Expanding Access to Sexual and Reproductive Health Services Through Nursing
      Education.
AB  - Thoughtful, unbiased, evidence-based content in nursing education is crucial for
      the development of confident and competent nurses who provide care in every
      setting. The purpose of this article is twofold: to provide evidence to show that
      comprehensive sexual and reproductive health care by nurses is informed by
      educational exposure to content and to provide recommendations for change at the
      individual, institutional, and structural levels to improve and expand sexual and
      reproductive health services.

PMID- 28499752
TI  - Principles of Supportive Psychotherapy for Perinatal Distress.
AB  - Although interpersonal psychotherapy and cognitive behavioral therapy have
      demonstrated efficacy in the treatment of perinatal distress, supportive
      psychotherapy has not been as widely studied by researchers. However, the
      principles of supportive psychotherapy are essential in the treatment of
      perinatal distress. The purpose of this article is to show that supportive
      psychotherapy is a plausible intervention that nurses and other maternity care
      providers can use with women who experience anxiety and depression in the
      perinatal period.

PMID- 28499753
TI  - Emotional intelligence and stress management in Nursing professionals in a
      hospital emergency department.
AB  - OBJECTIVE: To determine stress levels and to identify if there is a relationship
      between emotional intelligence and work stress in nurses and healthcare
      assistants of the Emergency Department. METHOD: Observational, descriptive and
      cross-sectional study with a quantitative approach. The population were nurses
      and healthcare assistants of the Emergency Department of the University Hospital
      of Ourense. The data were collected between January and May 2016. The tool used
      was a validated, anonymous, and self-administered questionnaire that included the
      Trait Meta-Mood Scale and Moreno's Brief Burnout Questionnaire. The study was
      approved by the Clinical Research Ethics Committee of Galicia. Descriptive and
      association analyses were performed using the SPSS 15.0 statistics program.
      RESULTS: A total of 60 professionals participated, of whom 36 were qualified
      nurses and 24 were auxiliary nurses. The response rate was 68.1%. The results
      showed a deficiency in emotional care, with a score of 22.87, while emotional
      clarity and reparation of emotions were situated within normal levels, with
      values of 26.42 and 26.60, respectively. The burnout levels of the sample were
      medium-high. The mean score in the depersonalisation dimension was 8.05, whereas
      emotional fatigue obtained a mean of 6.90, with a value of 7.50 for professional
      fulfilment. Significant positive correlations were found between the employment
      situation and emotional clarity (r=.276; P=.033), and between the latter and
      personal fulfilment (r=.277; P=.032), and organisation (r=.316; P=.014).
      CONCLUSIONS: Nurses and healthcare assistants of the Emergency Department showed
      medium-high average levels of burnout, with depersonalisation being the symptom
      that reflects the highest values. Emotional Intelligence is related to work
      stress and, specifically, the understanding of one's own emotional states
      influences personal fulfilment. Professionals with more job stability show a
      better capacity to feel and express their feelings.

PMID- 28499754
TI  - Methotrexate-induced epidermal necrosis: A case series of 24 patients.
AB  - BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life
      threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and
      toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the
      clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We
      enrolled 24 patients with MEN and 150 controls and analyzed the demographics,
      pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients
      with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but
      no target lesions. The histopathology displayed keratinocyte dystrophy. Early
      signs of MEN included painful skin erosions, oral ulcers, and
      leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin
      treatment, there was 16.7% mortality. Risk factors for MEN included older age
      (>60 years), chronic kidney disease, and high initial dosage of MTX without folic
      acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal
      disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of
      Toxic Epidermal Necrosis criteria were associated with mortality of MEN.
      LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN
      exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the
      early signs and prognostic factors is important, because the rapid institution of
      leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid
      prescribing MTX to high-risk patients and titrate the dosage slowly upward with
      folic acid supplementation.

PMID- 28499755
TI  - Biological characteristics and karyotiping of a new isolation method for human
      adipose mesenchymal stem cells in vitro.
AB  - OBJECTIVE: A new method was presented to prepare clinical-grade human adipose
      derived stromal stem cells (ASCs) and its safety in vitro, such as biological
      characteristics and genetic features alteration were investigated. METHODS: The
      morphology of the ASCs which were cultured in vitro using serum-free medium was
      observed. Cell cycle and CD markers profile were tested by flow cytometry, while
      karyotype was analyzed by the chromosome G-banding technology. Growth factors
      expression was tested by ELISA and tumor-related genes were analyzed by the real
      time PCR, respectively. RESULTS: ASCs were adult stem cells with spindle shape.
      The proliferation ratio of ASCs began to slow down after 10 passages, and was
      significant after 15 passages. Cell cycle analysis revealed that the percentage
      of G2 phase and S phase cells was stable. There was no obvious missing,
      translocation or dislocation in terms of karyotype. Expression level of tumor
      relevant genes and cytokines at different passages had no significant difference.
      CONCLUSIONS: The clinical-grade ASCs prepared with this new method, less than ten
      passages, was safe for clinical trials.

PMID- 28499757
TI  - Hidradenitis Suppurativa Is Associated with Familial Mediterranean Fever-A
      Population-Based Study.

PMID- 28499756
TI  - Genetic Variants in WNT2B and BTRC Predict Melanoma Survival.
AB  - Cutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an
      impact on development, invasion, and metastasis of CM, thus likely affecting CM
      prognosis. Using data from a published genome-wide association study from The
      University of Texas MD Anderson Cancer Center, we assessed the associations of
      19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal
      genes with CM-specific survival and then validated significant SNPs in another
      genome-wide association study from Harvard University. In the single-locus
      analysis, 1,855 SNPs were significantly associated with CM-specific survival at P
      < 0.05, of which 547 SNPs were still considered noteworthy after the correction
      by the false-positive report probability. In the replication, two SNPs remained
      significantly associated with CM-specific survival after multiple comparison
      correction. By performing functional prediction and stepwise selection, we
      identified two independent SNPs (i.e., WNT2B rs1175649 G>T and BTRC rs61873997
      G>A) that showed a predictive role in CM-specific survival, with an effect-allele
      attributed hazards ratio (adjusted hazards ratio) of 1.99 (95% confidence
      interval = 1.41-2.81, P = 8.10 * 10-5) and 0.61 (0.46-0.80, 3.12*10-4),
      respectively. Collectively, these variants in the Wnt pathway genes may be
      biomarkers for outcomes of patients with CM, if validated by larger studies.

PMID- 28499758
TI  - Activating CYSLTR2 and PLCB4 Mutations in Primary Leptomeningeal Melanocytic
      Tumors.

PMID- 28499759
TI  - Trends in Operating Room Assistance for Major Urologic Surgical Procedures: An
      Increasing Role for Advanced Practice Providers.
AB  - OBJECTIVE: To characterize changes in surgical assistance patterns over time for
      commonly performed urologic operations. MATERIALS AND METHODS: This study used
      the Medicare Physician/Supplier Procedure Summary Master File to identify cases
      performed by urologists from 2003 to 2014. Current Procedural Terminology
      modifiers were used to identify operations assisted by second surgeons and
      advanced practice providers (APPs). Rates were reported annually for 6 common
      urologic operations, and average annual rates of change were determined using
      least squares regression and tested using t tests (alpha = .05). RESULTS: Of the
      urologic operations analyzed, 5.0% of cases (n = 33,895) were assisted by APPs
      compared with 27.0% (n = 182,842) assisted by a second surgeon. The proportion of
      cases assisted by an APP rose significantly for all procedures; conversely, the
      proportion of cases assisted by a second surgeon declined significantly for all
      procedures, except for open partial nephrectomy. The largest changes were seen in
      robotic prostatectomies for which second surgeon assistance fell from 26% in 2004
      to 15% in 2014, whereas APP assistance rose from <1% to 7%. CONCLUSION:
      Urologists are increasingly using APPs as assistants in surgery, particularly in
      robotic and laparoscopic operations. This trend will likely continue as the
      shortage of urologists worsens in the coming years.

PMID- 28499760
TI  - Henoch-Schonlein Purpura With Testicular Necrosis: Sonographic Findings at the
      Onset, During Treatment, and at Follow-up.
AB  - Henoch-Schonlein purpura (HSP) with involvement of the testes is extremely rare.
      Here, we present a pediatric case of HSP involving testicular ischemic necrosis
      in an 8-year-old child. Ultrasonography plays an important role not only in the
      differential diagnosis at onset, but also in the assessment of treatment response
      and prognosis during treatment and at follow-up. In this case report, we present
      the sonographic images for the entire course of testicular involvement in HSP and
      reveal histopathologically the pathogeny as testicular autoimmune vasculitis
      caused by the deposition of immunoglobulin A-containing immune complexes in the
      testicular vessels.

PMID- 28499761
TI  - Cystadenoma of the Rete Testis in a Patient With von Hippel-Lindau Disease.
AB  - von Hippel-Lindau disease is a rare, inherited multicystic disorder that is
      characterized by several benign and malignant neoplasms (Odrzywolski, 2010).
      Classically, the disease manifests itself in a broad spectrum, including renal
      cell carcinomas, intracranial and spinal hemangioblastomas, endolymphatic sac
      tumors, renal and pancreatic cysts, and pheochromocytomas. Another important, but
      commonly forgotten manifestation is the cystadenoma of the rete testis.

PMID- 28499762
TI  - Ureteral Wall Thickness as a Preoperative Indicator of Impacted Stones in
      Patients With Ureteral Stones Undergoing Ureteroscopic Lithotripsy.
AB  - OBJECTIVE: To evaluate the clinical significance of ureteral wall thickness (UWT)
      to predict the presence of impacted stones in patients with ureteral stones
      undergoing ureteroscopic lithotripsy (URSL). MATERIALS AND METHODS: We
      retrospectively analyzed 130 procedures in patients with ureteral stones who
      underwent URSL between January 2014 and September 2016. Maximum UWT at the stone
      site was measured from computed tomography images. Clinical predictors of
      impacted stones were assessed using univariate and multivariate logistic
      regression analyses. Receiver operating characteristic curve analysis was applied
      to determine the UWT cutoff value and to evaluate its accuracy in predicting
      impacted stones. Moreover, we evaluated the association between UWT and
      endoscopic findings, as well as surgical outcomes. RESULTS: Of the 130
      procedures, 50 (38.5%) involved patients with impacted stones. The univariate
      analysis showed significant differences in age, hydronephrosis, stone location,
      stone burden, and UWT in patients with and without impacted stones, and the
      multivariate analysis showed that age, stones in the middle ureter, and UWT (odds
      ratio 5.43, P < .001) were independent predictors of impacted stones. The
      receiver operating characteristic analysis showed that 3.49 mm was the optimal
      cutoff value for UWT, with a predictive accuracy of 0.87. High UWTs were
      associated with the presence of ureteral edema, polyps, white lesions, stone
      fixation, longer operation time, and lower endoscopic stone-free rate, compared
      with low UWTs (P < .05 each). CONCLUSION: High UWT is associated not only with a
      higher risk of impacted stones but also with poor endoscopic findings and adverse
      surgical outcomes in patients with ureteral stones undergoing URSL.

PMID- 28499763
TI  - Hydronephrosis Secondary to an Ectopic Decidual Reaction in the Urinary Bladder.
AB  - A 28-year-old pregnant woman at 19 weeks gestation presented with dysuria as well
      as lower abdominal and left flank pain. Imaging revealed left-sided
      hydronephrosis and a mass invading the posterior bladder wall. Management
      included placement of a left nephrostomy tube and transurethral resection of ~25%
      of the mass. Microscopy showed an ectopic decidual reaction within the muscularis
      propria. The patient improved symptomatically and continued prenatal care.
      Complete resolution of her ureteral obstruction was demonstrated during the
      postpartum period. Ectopic decidual reactions involving the urinary bladder are
      extremely rare, and ureteral obstruction secondary to this phenomenon has not yet
      been reported.

PMID- 28499764
TI  - [Personal health records on the Internet. A narrative review of attitudes,
      expectations, utilization and effects on health outcomes].
AB  - BACKGROUND: The integration of information and communication technologies (ICT)
      is increasingly considered in the development of healthcare structures. This fact
      is also recognised in the e-Health Act. In this context, personal health records
      (PHR) have a specific meaning. The aim of this paper is to provide an overview on
      utilization, barriers and possible effects on the implementation of PHR. METHODS:
      This analysis is based on a literature search in Web of Science (Core Collection)
      (01/2000 to 12/2014) using the following terms: "personal health record",
      "personal medical record", "personal electronic health record", "interpersonal
      health record", "personally controlled health record". RESULTS: In general,
      patients have positive attitudes towards the electronic exchange of personal
      health information (PHI) on a PHR. Even the sharing of PHI with physicians,
      health professionals, family and friends appears to be an option for many
      patients. Physicians also see the potential of a PHR on the internet, but they
      are more critical than patients. Barriers exist towards the use of complex and
      non-intuitive PHR concepts along with technical faults and the lack of
      functionality. From the physicians' perspective, prejudices concerning the use of
      PHR have not been confirmed and, other than previously expected, the workload has
      not increased so much. However, clinical outcomes have so far been rather
      moderate. Stronger effects may be achieved by embedding the PHR in a broader
      healthcare concept. CONCLUSION: In the context of chronic disease, a connected
      PHR (patient-controlled, cross-sectoral, and interoperable) can be a valuable
      tool for organizing healthcare for patients. To take full effect, the development
      of such systems should focus on patients and their families as well as on
      physicians and other healthcare professionals. Whether the e-Health Act is a step
      in the right direction will have to be established by future analysis.

PMID- 28499765
TI  - CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing
      in HIV-infected patients.
AB  - OBJECTIVES: To evaluate concordance between glomerular filtration rate (GFR)
      estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic
      kidney disease epidemiology study group equations) for drug dosing in HIV
      infected patients. PATIENTS AND METHODS: We performed a monocentric study. GFR
      was measured using the gold standard method (plasma clearance of iohexol) in 230
      HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR)
      and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90
      mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and
      without indexation to body surface area (BSA). RESULTS: Mean age was 48+/-10
      years, mean mGFR was 101+/-26 mL/min. Concordance between mGFR and eGFR estimated
      with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed
      to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value
      of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD
      indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as
      the breakpoint value, all equations had similar concordance rates with mGFR (with
      or without indexation to BSA). CONCLUSION: CKD-EPI equation has the same
      concordance with GFR and with CG when used for drug dosing.

PMID- 28499766
TI  - Comparing early signs and basic symptoms as methods for predicting psychotic
      relapse in clinical practice.
AB  - BACKGROUND: Early signs interventions show promise but could be further
      developed. A recent review suggested that 'basic symptoms' should be added to
      conventional early signs to improve relapse prediction. This study builds on
      preliminary evidence that basic symptoms predict relapse and aimed to: 1. examine
      which phenomena participants report prior to relapse and how they describe them;
      2. determine the best way of identifying pre-relapse basic symptoms; 3. assess
      current practice by comparing self- and casenote-reported pre-relapse
      experiences. METHODS: Participants with non-affective psychosis were recruited
      from UK mental health services. In-depth interviews (n=23), verbal checklists of
      basic symptoms (n=23) and casenote extracts (n=208) were analysed using directed
      content analysis and non-parametric statistical tests. RESULTS: Three-quarters of
      interviewees reported basic symptoms and all reported conventional early signs
      and 'other' pre-relapse experiences. Interviewees provided rich descriptions of
      basic symptoms. Verbal checklist interviews asking specifically about basic
      symptoms identified these experiences more readily than open questions during in
      depth interviews. Only 5% of casenotes recorded basic symptoms; interviewees were
      16 times more likely to report basic symptoms than their casenotes did.
      CONCLUSIONS: The majority of interviewees self-reported pre-relapse basic
      symptoms when asked specifically about these experiences but very few casenotes
      reported these symptoms. Basic symptoms may be potent predictors of relapse that
      clinicians miss. A self-report measure would aid monitoring of basic symptoms in
      routine clinical practice and would facilitate a prospective investigation
      comparing basic symptoms and conventional early signs as predictors of relapse.

PMID- 28499767
TI  - Routine patient reported outcomes as predictors of psychiatric rehospitalization.
AB  - OBJECTIVE: Patient reported outcome measures (PROMs) are increasingly used to
      measure psychiatric service consumers' progress and to provide feedback to
      consumers and providers. We tested whether PROMs can predict and be used to
      identify groups at high risk for future hospitalization. METHODS: A total of 2842
      Israeli users of psychiatric rehabilitation services reported on their quality of
      life (QoL) and the effect of symptoms on their daily functioning. Survey data
      were linked with information on psychiatric hospitalization 6 and 12months after
      survey completion. Variables associated with each of the outcomes were tested for
      significance and entered into a multivariate logistic regression model.
      Prediction scores were developed to identify the highest-risk groups according to
      each model. RESULTS: QoL was found to be a significant predictor of future
      hospitalization within 6months (odds ratio [OR]=0.71, 95% CI: 0.59-0.86), and
      self-report of the impact of symptoms on functioning significantly predicted 12
      month hospitalization (OR=0.83, 95% CI: 0.74-0.93), controlling for known risk
      factors. Positive predictive values for the 6- and 12-month risk scores were 31.1
      and 40.4, respectively, for the 10% highest risk categories. CONCLUSIONS: Reports
      of psychiatric service consumers on their QoL and on the effect of symptoms on
      their functioning significantly predict of future hospitalization risk, beyond
      other well-known risk factors. PROMs can identify consumers at high risk for
      future hospitalization and thus direct interventions for those at highest risk.

PMID- 28499768
TI  - Mortality in people with psychotic disorders in Finland: A population-based 13
      year follow-up study.
AB  - OBJECTIVES: We conducted a population based study aiming at finding predictors of
      mortality in psychotic disorders and evaluating the extent to which
      sociodemographic, lifestyle and health-related factors explain the excess
      mortality. METHODS: In a nationally representative sample of Finns aged 30
      70years (n=5642), psychotic disorders were diagnosed using structured interviews
      and medical records in 2000-2001. Information on mortality and causes of death
      was obtained of those who died by the end of year 2013. Cox proportional hazards
      models were used to investigate the mortality risk. RESULTS: No people with
      affective psychoses (n=36) died during the follow-up, thus the analysis was
      restricted to non-affective psychotic disorders (NAP) (n=106). Adjusting for age
      and sex, NAP was statistically significantly associated with all-cause mortality
      (hazard ratio (HR) 2.99, 95% CI 2.03-4.41) and natural-cause mortality (HR 2.81,
      95% CI 1.85-4.28). After adjusting for sociodemographic factors, health status,
      inflammation and smoking, the HR dropped to 2.11 (95% CI 1.10-4.05) for all-cause
      and to 1.98 (95% CI 0.94-4.16) for natural-cause mortality. Within the NAP group,
      antipsychotic use at baseline was associated with reduced HR for natural-cause
      mortality (HR 0.25, 95% CI 0.07-0.96), and smoking with increased HR (HR 3.54,
      95% CI 1.07-11.69). CONCLUSIONS: The elevated mortality risk in people with NAP
      is only partly explained by socioeconomic factors, lifestyle, cardio-metabolic
      comorbidities and inflammation. Smoking cessation should be prioritized in
      treatment of psychotic disorders. More research is needed on the quality of
      treatment of somatic diseases in people with psychotic disorders.

PMID- 28499769
TI  - Structure, biochemical and kinetic properties of recombinant Pst2p from
      Saccharomyces cerevisiae, a FMN-dependent NAD(P)H:quinone oxidoreductase.
AB  - The genome of the yeast Saccharomyces cerevisiae encodes four flavodoxin-like
      proteins, namely Lot6p, Pst2p, Rfs1p and Ycp4p. Thus far only Lot6p was
      characterized in detail demonstrating that the enzyme possesses NAD(P)H:quinone
      oxidoreductase activity. In the present study, we heterologously expressed PST2
      in Escherichia coli and purified the produced protein to conduct a detailed
      biochemical and structural characterization. Determination of the three
      dimensional structure by X-ray crystallography revealed that Pst2p adopts the
      flavodoxin-like fold and forms tetramers independent of cofactor binding. The
      lack of electron density for FMN indicated weak binding, which was confirmed by
      further biochemical analysis yielding a dissociation constant of 20+/-1MUM. The
      redox potential of FMN bound to Pst2p was determined to -89+/-3mV and is thus
      119mV more positive than that of free FMN indicating that reduced FMN binds ca.
      five orders of magnitude tighter to Pst2p than oxidized FMN. Due to this rather
      positive redox potential Pst2p is unable to reduce free FMN or azo dyes as
      reported for other members of the flavodoxin-like protein family. On the other
      hand, Pst2p efficiently catalyzes the NAD(P)H dependent two-electron reduction of
      natural and artificial quinones. The kinetic mechanism follows a ping-pong bi-bi
      reaction scheme. In vivo experiments with a PST2 knock out and overexpressing
      strain demonstrated that Pst2p enables yeast cells to cope with quinone-induced
      damage suggesting a role of the enzyme in managing oxidative stress.

PMID- 28499770
TI  - Development of active, nanoparticle, antimicrobial technologies for muscle-based
      packaging applications.
AB  - Fresh and processed muscle-based foods are highly perishable food products and
      packaging plays a crucial role in providing containment so that the full effect
      of preservation can be achieved through the provision of shelf-life extension.
      Conventional packaging materials and systems have served the industry well,
      however, greater demands are being placed upon industrial packaging formats owing
      to the movement of muscle-based products to increasingly distant markets, as well
      as increased customer demands for longer product shelf-life and storage
      capability. Consequently, conventional packaging materials and systems will have
      to evolve to meet these challenges. This review presents some of the new
      strategies that have been developed by employing novel nanotechnological concepts
      which have demonstrated some promise in significantly extending the shelf-life of
      muscle-based foods by providing commercially-applicable, antimicrobially-active,
      smart packaging solutions. The primary focus of this paper is applied to subject
      aspects, such as; material chemistries employed, forming methods utilised,
      interactions of the packaging functionalities including nanomaterials employed
      with polymer substrates and how such materials ultimately affect microbes. In
      order that such materials become industrially feasible, it is important that
      safe, stable and commercially-viable packaging materials are shown to be
      producible and effective in order to gain public acceptance, legislative approval
      and industrial adoption.

PMID- 28499771
TI  - The key role of the meat industry in transformation to a low-carbon, climate
      resilient, sustainable economy.
AB  - Climate change, air pollution and refugees have become key global challenges
      threatening sustainability of lifestyles, economies and ecosystems. Agri-food
      systems are the number one driver of environmental change. Livestock production
      is the world's largest land user, responsible for half of greenhouse gas
      emissions from agri-food systems, and the source of repeated health crises. Poor
      diets have become the number one cause of ill health. Recommendations for a
      healthy diet emphasize plant-based food. Rapidly falling costs in information
      technology, biotechnology, renewable energy and battery technology will disrupt
      current energy and transportation systems and offer opportunities for responsible
      meat production. Growing consumer interest in healthy food, combined with
      innovative information systems, offer opportunities to create value through
      quality control and consumer information in integrated value chains. Meat
      scientists have a major role to play in the necessary transformation of global
      agri-food systems towards a new model of green economic growth that is climate
      resilient, sustainable and provides green jobs.

PMID- 28499772
TI  - Exploring Patient Engagement: A Qualitative Analysis of Low-Income Urban
      Participants in Asthma Research.
AB  - BACKGROUND: Uncontrolled asthma is a common highly morbid condition with worse
      outcomes in low-income and minority patients in part due to barriers accessing
      and engaging with health care. We developed a patient advocate to educate about
      and assist with navigating access to care and provider-patient communication.
      Participants completed an End of Study Questionnaire (ESQ) that was analyzed to
      assess experience and engagement with the protocol. OBJECTIVE: This study uses
      qualitative analysis to evaluate participant experience with the patient advocate
      and control group interventions. METHODS: The ESQ aimed to prompt an open-ended
      discussion of study experience. Questions were developed from patient focus
      groups about the patient advocate intervention (PAI), and were revised based on
      early responses. The questionnaire was administered after 12 months of study
      participation: 6 months of control or PAI, followed by 6 months of follow-up.
      Answers were evaluated using qualitative coding and a grounded theory analytical
      approach. RESULTS: A total of 102 low-income and minority adults with moderate or
      severe asthma who had completed the study protocol at the time of publication
      (approximately one-third of total participants) found PAI and control group
      activities acceptable. Four themes emerged from both groups: (1) appreciation of
      interpersonal and educational interaction, (2) perception of improved health care
      adherence, (3) preparedness for physician appointments, (4) improved patient
      provider communication. Attention from study personnel and review of asthma
      related information was unanimously well received and empowered patients' active
      health care participation. CONCLUSIONS: Patient engagement and empowerment were
      elicited by perceived education and personal attention. This study suggests a low
      resource, feasible method to improve patient engagement.

PMID- 28499773
TI  - Stability of Asthma Symptom Control in a Longitudinal Study of Mild-Moderate
      Asthmatics.
AB  - BACKGROUND: Achieving and maintaining symptom control is a primary goal of asthma
      management. Although factors associated with the likelihood of achieving symptom
      control have been studied, there are unanswered questions on the stability of
      symptom control, that is, the tendency of individuals to remain at a given
      symptom control level over time. OBJECTIVE: The objective of this study was to
      evaluate the stability of symptom control using a longitudinal cohort of mild
      moderate asthmatics. METHODS: Participants reported symptom control using the
      Global Initiative for Asthma criteria at 5 assessments during the 1-year follow
      up period. We described variability in the stability of symptom control between
      individuals, and used a random-effects logistic regression model to evaluate the
      impact of a suite of factors on the stability of symptom control. RESULTS: A
      total of 429 individuals (67% female, mean age 51.6) contributed 2141 study
      visits. Individuals varied from completely stable in symptom control (18%
      remained at the same control level in all 5 visits) to completely unstable (12%
      changed the control level between all subsequent visits). Only 4% of between
      individual variation in the stability of symptom control was explained by the
      included exposures, and a secondary analysis indicated that the history of
      symptom control stability was the best predictor of current stability.
      CONCLUSIONS: The tendency to remain at a given control level varies significantly
      among patients with asthma. Only a small fraction of this variability is
      explained by observable characteristics. In the absence of predictors, a previous
      history of symptom control stability is the best indicator of future stability
      and should be considered when monitoring symptom control.

PMID- 28499774
TI  - An Australian Consensus on Infant Feeding Guidelines to Prevent Food Allergy:
      Outcomes From the Australian Infant Feeding Summit.
AB  - BACKGROUND: Infant feeding in the first postnatal year of life has an important
      role in an infant's risk of developing food allergy. Consumer infant feeding
      advice is diverse and lacks consistency. AIM: The Australian Infant Feeding
      Summit was held with the aim of achieving national consensus on the wording of
      guidelines for infant feeding and allergy prevention. METHODS: Two meetings were
      hosted by the Centre for Food and Allergy Research, the Australasian Society of
      Clinical Immunology and Allergy, and the Australian National Allergy Strategy.
      The first meeting of 30 allergy researchers, clinicians, and consumers assessed
      the evidence. The second consensus meeting involved 46 expert stakeholders
      including state and federal health care agencies, consumers, and experts in
      allergy, infant feeding, and population health. RESULTS: Partner stakeholders
      agreed on consensus wording for infant feeding advice: CONCLUSIONS: Consensus was
      achieved in a context in which there is a high prevalence of food allergy.
      Guidelines for other countries are being updated. Provision of consistent wording
      related to infant feeding to reduce food allergy risk will ensure clear consumer
      advice.

PMID- 28499775
TI  - Precision allergy: Separate allergies to male and female dogs.

PMID- 28499776
TI  - Seminal plasma hypersensitivity: Clinical and histopathologic features in a
      multipara woman.

PMID- 28499778
TI  - Fatal Anaphylaxis to Yellow Jacket Stings in Mastocytosis: Options for
      Identification and Treatment of At-Risk Patients.
AB  - BACKGROUND: Patients with indolent systemic mastocytosis (ISM) are at risk for
      severe anaphylactic reactions to yellow jacket (YJ) stings while demonstration of
      sensitization can be challenging because specific IgE (sIgE) levels are regularly
      below 0.35 kUA/L. The implication of missing YJ allergy is illustrated by a case
      of fatal anaphylaxis. OBJECTIVE: To explore the natural course of YJ venom
      allergy and the diagnostic accuracy and therapeutic consequence of YJ venom sIgE
      in patients with ISM. METHODS: All patients with ISM seen from 1981 to 2015 (n =
      243) were evaluated on the number of YJ stings, reaction severity, and
      sensitivity and specificity of YJ venom sIgE. YJ venom allergic patients without
      mastocytosis served as control (n = 313). RESULTS: A total of 153 patients with
      ISM were stung during adult life. The first systemic reaction was more often
      severe in patients with ISM than in patients without mastocytosis (69.9% vs
      22.0%) and reactions recurred in 40 of 41 re-stung patients with ISM. ISM
      reactors showed lower YJ venom sIgE levels than nonmastocytosis reactors (0.61 vs
      4.83 kUA/L; P < .001) and asymptomatic sensitization was exceedingly rare. In ISM
      the current clinical threshold of 0.35 kUA/L yields a sensitivity and specificity
      of 77.6% and 87.5%, respectively. The optimal diagnostic accuracy is achieved at
      0.17 kUA/L (sensitivity, 83.6%; specificity, 85.0%). CONCLUSIONS: The high rate
      of severe reactions and the fatal case underscore the importance of adequate
      diagnostic sensitivity of sIgE in patients with ISM. The sensitivity of sIgE can
      be ameliorated by lowering the threshold to 0.17 kUA/L, retaining good
      specificity. We recommend sIgE screening in all patients with ISM and discussing
      immunotherapy when YJ venom sIgE exceeds 0.17 kUA/L.

PMID- 28499777
TI  - Lack of Efficacy of Symptoms and Medical History in Distinguishing the Degree of
      Eosinophilia in Nasal Polyps.
AB  - BACKGROUND: Distinguishing eosinophilic nasal polyps (NP) from noneosinophilic NP
      will impact prognosis and therapeutic responsiveness. OBJECTIVE: To investigate
      the ability of clinical history and biomarkers to distinguish these conditions.
      METHODS: A total of 74 consecutive patients undergoing surgery for NP were
      enrolled. Clinical presentations were evaluated using the 22-item sinonasal
      outcome test (SNOT-22). Biomarkers included absolute eosinophil count, IgE, and
      extent of tissue hyperplasia on sinus computed tomography scan. Tissue
      eosinophilia was quantified in 10 random hpf and data analyzed addressing both
      peak and average results. RESULTS: No component of the SNOT-22 was predictive of
      tissue eosinophilia. Similarly, a medical history of allergic rhinitis, asthma,
      or aspirin-exacerbated respiratory disease was not predictive. An absolute
      eosinophil count of more than 300 was associated with NP tissue eosinophilia. In
      contrast, neither IgE nor extent of sinus computed tomography hyperplasia was
      predictive. CONCLUSIONS: The ability to individualize therapies for NP is
      dependent on identifying clinical features or biomarkers of eosinophilia.
      However, with the exception of circulating eosinophilia, we could not identify a
      clinical feature or biomarker that robustly predicted the presence of tissue
      eosinophilia. Even more problematic, even the seeming "criterion standard"
      determination of tissue pathology was of limited value, as our cohort displayed a
      continuous spectrum of tissue eosinophil expression, making arbitrary any
      definitive cutoff distinguishing these conditions.

PMID- 28499779
TI  - "Treating Through" Decision and Follow-up in Antibiotic Therapy-Associated
      Exanthemas.
AB  - BACKGROUND: Immediate discontinuation or replacement of suspected drugs is
      considered standard medical care in acute exanthematous skin reactions. In the
      treatment of bacterial infections, structurally different alternative
      antibiotics, however, are commonly second choice options due to a suboptimal
      antimicrobial activity or an unfavorable side effect profile. Nonetheless,
      "treating through," the continuation of antibiotic treatment despite an objective
      exanthema, is practiced only rarely. OBJECTIVE: We aimed to assess whether
      "treating through" is an option for patients with severe bacterial soft tissue
      infections (severe cellulitis) who experience maculopapular exanthema (MPE)
      during antibiotic therapy. METHODS: We retrospectively reviewed clinical data
      from 18 patients who developed MPE within a few days after initiation of
      intravenous antibiotic treatment. A decision to "treat through" was made when the
      suspected antibiotics (beta-lactams, clindamycin, ciprofloxacin) were clinically
      effective and the benefits of continued treatment outweighed potential risks.
      Clinical and laboratory findings were closely monitored in an inpatient setting.
      RESULTS: In 2 patients, a modification of antibiotic therapy was deemed necessary
      due to a significant increase of liver enzymes within 4 days after the initial
      decision to "treat through." Because of a progression of MPE under ongoing
      treatment with cefuroxime and clindamycin, clindamycin was discontinued in 1
      patient. In another 3 patients, antibiotic treatment was modified because of
      insufficient improvement of the soft tissue infection. In the remaining 12
      "treated through" cases, the skin symptoms improved despite unchanged continued
      antibiotic treatment, and relevant laboratory parameters remained within the
      normal range. CONCLUSIONS: Careful risk-benefit assessment may enable the
      continuation of antibiotic therapy despite MPE, provided that patients are under
      close medical observation.

PMID- 28499780
TI  - Drug-induced enterocolitis in an adult patient.

PMID- 28499781
TI  - Aplastic anemia and cytotoxic T lymphocyte antigen-4 haploinsufficiency treated
      with bone marrow transplantation.

PMID- 28499782
TI  - Systemic reactions to immunotherapy during mountain cedar season: implications
      for seasonal dose adjustment.

PMID- 28499783
TI  - CD21 deficiency in 2 siblings with recurrent respiratory infections and
      hypogammaglobulinemia.

PMID- 28499784
TI  - GSK-3 as a novel prognostic indicator in leukemia.
AB  - While leukemias represent a diverse set of diseases with malignant cells derived
      from myeloid or lymphoid origin, a common feature is the dysregulation of signal
      transduction pathways that influence leukemogeneisis, promote drug resistance,
      and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream
      regulators can activate the AKT kinase which has central roles in supporting cell
      proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3
      (GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of
      metabolism but emerged as central players in cancer in the early 1990s. GSK3 is
      unique in that the isoforms are constitutively active. Active GSK3 promotes
      destruction of oncogenic proteins such as beta Catenin, c-MYC, and MCL-1 and thus
      has tumor suppressor properties. In AML, inactivation of GSK3 is associated with
      poor overall survival. Interestingly in some leukemias GSK3 targets a tumor
      suppressor and thus the kinases can act as tumor promoters in those instances. An
      example is GSK3 targeting p27Kip1 in AML with MLL translocation. This review will
      cover the role of GSK3 in various leukemias both as tumor suppressor and tumor
      promoter. We will also briefly cover current state of GSK3 inhibitors for
      leukemia therapy.

PMID- 28499785
TI  - Antecedents of basic psychological need satisfaction of pharmacy students: The
      role of peers, family, lecturers and workload.
AB  - BACKGROUND: Self-determination theory (SDT) provides a model to improve pharmacy
      students' well-being or functioning in their study context. According to SDT,
      students need a context that satisfies their needs for autonomy, relatedness and
      competence in order to function optimally. Contextual factors that could have an
      impact on a student's functioning are lecturers, family, peers and workload.
      OBJECTIVES: To investigate whether there is a difference between the
      contributions family, lecturers, peers and workload make towards the satisfaction
      of pharmacy students' basic psychological needs within a university context.
      METHODS: An electronic survey was administered amongst students registered with
      the North-West University's School of Pharmacy. Registered pharmacy students,
      779, completed said electronic survey comprised of a questionnaire on
      demographics, BMPN (Balanced Measure of Psychological Needs) and self-developed
      ANPNS (Antecedents of Psychological Need-satisfaction Scale). Data derived from
      the afore-going was analysed with the aid of structural equation modelling (SEM).
      RESULTS: Structural equation modelling explained 46%, 25% and 30% respectively of
      the total group's variances in autonomy, competence and relatedness satisfaction,
      and 26% of the variance in psychological need frustration. Peers and family
      played a significant role in the satisfaction of students' need for autonomy,
      relatedness and competence, whilst workload seemingly hampered satisfaction with
      regards to relatedness and autonomy. Workload contributed towards frustration
      with regards to psychological need satisfaction. The role played by lecturers in
      satisfying pharmacy students' need for autonomy, relatedness and competence will
      also be highlighted. CONCLUSIONS: This study added to the body of knowledge
      regarding contextual factors and the impact those factors have on pharmacy
      students' need satisfaction by illustrating that not all factors (family,
      lecturers, peers and workload) can be considered equal. Lecturers ought to
      recognise the important role family and peers play in the emotional and mental
      wellbeing of students and utilise those factors in their teaching. SYNOPSIS: The
      mechanism of basic psychological need satisfaction as described in Self
      determination theory provide insight into pharmacy students' optimal functioning.
      Hence the influence of contextual factors, (lecturers, peers, family and
      workload) on the need satisfaction was investigated by means of a survey. The
      structural model explained 46%, 25% and 30% of the variances in autonomy,
      competence and relatedness satisfaction and 26% of the variance in psychological
      need frustration. Family and Peer support contributed the most to the variance
      explained of the variables. Lecturers should acknowledge this important role of
      family and peers and utilise this premise when they design learning encounters.

PMID- 28499786
TI  - Head elevation and lateral head rotation effect on facemask ventilation
      efficiency: Randomized crossover trials.
AB  - PURPOSE: We performed two prospective randomized crossover trials to evaluate the
      effect of head elevation or lateral head rotation to facemask ventilation volume.
      METHODS: In the first trial, facemask ventilation was performed with a 12-cm high
      pillow (HP) and 4-cm low pillow (LP) in 20 female patients who were scheduled to
      undergo general anesthesia. In the second trial, facemask ventilation was
      performed with and without lateral head rotation in another 20 female patients.
      Ventilation volume was measured in a pressure-controlled ventilation (PCV) manner
      at 10, 15, and 20 cmH2O inspiratory pressures. RESULTS: In the first trial
      evaluating head elevation effect, facemask ventilation volume was significantly
      higher with a HP than with a LP at 15 and 20 cmH2O inspiratory pressure (15
      cmH2O: HP median540 [IQR480-605] mL, LP 460 [400-520] mL, P=0.006, 20 cmH2O: HP
      705 [650-800] mL, LP 560 [520-677] mL, P<0.001). In the second trial, lateral
      head rotation did not significantly increase facemask ventilation volume at all
      inspiratory pressure. CONCLUSION: Head elevation increased facemask ventilation
      volume in normal airway patients, while lateral head rotation did not.

PMID- 28499787
TI  - Motocross-associated head and spine injuries in adult patients evaluated in an
      emergency department.
AB  - BACKGROUND: Motor vehicle-related injuries (including off-road) are the leading
      cause of traumatic brain injury (TBI) and acute traumatic spinal cord injury in
      the United States. OBJECTIVES: To describe motocross-related head and spine
      injuries of adult patients presenting to an academic emergency department (ED).
      METHODS: We performed an observational cohort study of adult ED patients
      evaluated for motocross-related injuries from 2010 through 2015. Electronic
      health records were reviewed and data extracted using a standardized review
      process. RESULTS: A total of 145 motocross-related ED visits (143 unique
      patients) were included. Overall, 95.2% of patients were men with a median age of
      25years. Sixty-seven visits (46.2%) were associated with head or spine injuries.
      Forty-three visits (29.7%) were associated with head injuries, and 46 (31.7%)
      were associated with spine injuries. Among the 43 head injuries, 36 (83.7%) were
      concussions. Seven visits (16.3%) were associated with at least 1 head
      abnormality identified by computed tomography, including skull fracture (n=2),
      subdural hematoma (n=1), subarachnoid hemorrhage (n=4), intraparenchymal
      hemorrhage (n=3), and diffuse axonal injury (n=3). Among the 46 spine injuries,
      32 (69.6%) were acute spinal fractures. Seven patients (4.9%) had clinically
      significant and persistent neurologic injuries. One patient (0.7%) died, and 3
      patients had severe TBIs. CONCLUSION: Adult patients evaluated in the ED after
      motocross trauma had high rates of head and spine injuries with considerable
      morbidity and mortality. Almost half had head or spine injuries (or both), with
      permanent impairment for nearly 5% and death for 0.7%.

PMID- 28499788
TI  - Nocturia and Prevalence of Depressive Symptoms in Japanese Adult Patients With
      Type 2 Diabetes Mellitus: The Dogo Study.
AB  - OBJECTIVES: No studies have investigated the association between nocturia and
      depressive symptoms in patients with type 2 diabetes mellitus. Because nocturia
      and depressive symptoms are common in patients with type 2 diabetes, we examined
      this association in Japanese patients with type 2 diabetes. METHODS: We studied
      762 Japanese patients with type 2 diabetes. A self-administered questionnaire was
      used to collect information about the variables under study. The subjects were
      divided into 3 groups according to their nocturnal micturition: 1) no nocturia;
      2) mild nocturia (1 void per night) and 3) moderate to severe nocturia (2 or more
      voids per night). Depressive symptoms were defined as being present when a
      subject had a Self-Rating Depression Scale score higher than 49. RESULTS: The
      prevalence values of mild nocturia, moderate to severe nocturia and depressive
      symptoms were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and
      moderate to severe nocturia were independently positively associated with
      depressive symptoms in all patients; the adjusted ORs were 1.96 (95% CI 1.06 to
      3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and
      moderate to severe nocturia were independently associated with depressive
      symptoms; the adjusted ORs were 5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15
      to 28.54), respectively. In male patients, neither mild nocturia nor moderate to
      severe nocturia was significantly related to depressive symptoms. CONCLUSIONS: In
      Japanese female patients with type 2 diabetes, nocturia may be positively
      associated with depressive symptoms.

PMID- 28499789
TI  - Association Between the Polymorphism of Glu298Asp in Exon 7 of the eNOS Gene With
      Foot Ulcer and Oxidative Stress in Adult Patients With Type 2 Diabetes.
AB  - OBJECTIVES: Diabetic foot ulcer (DFU) is a common and major manifestation in
      patients with diabetes. Oxidative stress (OS) plays an important role in diabetic
      complications, such as DFU. Nitric oxide deficiency contributes to the impairment
      of diabetic wound healing. The aim of this study was to examine the association
      between the eNOS Glu298Asp polymorphism and DFU and oxidative stress in patients
      with type 2 diabetes mellitus in an Iranian population. METHODS: In this case
      control study, 123 patients with type 2 diabetes and DFU and 134 patients without
      DFU were recruited. The genotypes of eNOS Glu298Asp polymorphism in exon 7 were
      determined by the polymerase chain reaction-restriction fragment length
      polymorphism analysis. We measured the levels of thiobarbituric reactive
      substances and ferric-reducing ability of plasma as the potential markers of OS.
      RESULTS: There were significant differences in genotype frequencies of eNOS
      Glu298Asp polymorphism between case and control groups (GG+TG vs. TT; p=0.002;
      OR=0.22, 95% CI 0.83 to 0.62). Also, the frequency of the T allele in cases was
      less common than in controls (p=0.004). There was no significant difference in
      levels of OS parameters and various genotypes (p>0.05). CONCLUSIONS: These
      results imply that the T allele might be protective against DFU.

PMID- 28499790
TI  - Trends in Blood Glucose Test Strip Utilization: A Population-Wide Analysis in
      Saskatchewan, Canada.
AB  - OBJECTIVES: To describe trends in blood glucose test strip (TS) utilization and
      cost in Saskatchewan. METHODS: A retrospective analysis of TS use between January
      1, 1996, and December 31, 2013, was conducted using population-based health
      administrative databases in Saskatchewan. The prescription drug database was used
      to describe the annual number of TS dispensations, the number of strips
      dispensed, the number of unique beneficiaries and the total costs. A patient
      level analysis was also carried out to describe the patterns of TS use (i.e.
      light, moderate or heavy) by the entire cohort and by diabetes treatments.
      Potential cost savings due to a newly implemented restriction policy were
      estimated based on the most recent data (2013). RESULTS: TS utilization increased
      dramatically between 1996 and 2013 in terms of the number of users and the
      average number of TSs received. The percentage of TS users receiving fewer than 4
      TSs per week (i.e. light users) decreased by 20%, while the percentage of heavy
      users (i.e. those receiving more than 8 TSs per week) increased by 19%. During
      the same period, the use of high-risk oral hypoglycemic medications declined by
      30% among all TS users. Heavy TS use was observed in at least one-third of all
      users, irrespective of treatment type. CONCLUSIONS: If Saskatchewan's newly
      imposed coverage limits had been applied in 2013, the costs of strips exceeding
      those limits would have totalled $2.5 million. Although TS use aligns with
      chronic disease care paradigms, the substantial costs and lack of evidence of
      patient outcomes demand better strategies to help reduce unnecessary use.

PMID- 28499792
TI  - Doing More With Less; Are There Some 'Easy Wins' in the Management of Early
      Breast Cancer?

PMID- 28499791
TI  - The Role of Radiotherapy in Epidermal Growth Factor Receptor Mutation-positive
      Patients with Oligoprogression: A Matched-cohort Analysis.
AB  - AIMS: Almost all patients with epidermal growth factor receptor (EGFR) mutations
      will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The
      management of oligoprogression on EGFR TKI is controversial. Irradiating
      progressing tumours may potentially eradicate the resistant clone and allow
      continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess
      the effect of radiotherapy on survival outcomes in patients with oligoprogression
      in a matched-cohort study. MATERIALS AND METHODS: This was a retrospective
      matched-cohort study comparing patients with EGFR mutation-positive stage IV non
      small cell lung cancer receiving radiotherapy versus chemotherapy for
      progression. Patients in the radiotherapy group received radiotherapy (mainly
      stereotactic ablative radiotherapy) for oligoprogression, whereas the
      chemotherapy group received only systemic chemotherapy upon progression. Key
      prognostic factors including gender, age, performance status, time to first
      progression and mutation subtypes were matched. RESULTS: Twenty-five patients
      with oligoprogression (radiotherapy group) were identified, and a matched
      chemotherapy group with the same number of patients was generated. The median
      duration of follow-up was 24.3 and 34 months for the radiotherapy and
      chemotherapy groups, respectively. The median overall survival of the
      radiotherapy group was significantly longer than the chemotherapy group, 28.2
      versus 14.7 months (P = 0.026). The median progression-free survival (PFS) was
      7.0 and 4.1 months after radiotherapy and chemotherapy, respectively (P =
      0.0017). The use of radiotherapy was an independent predictive factor of overall
      survival and PFS in multivariate analysis. Only one patient had >=grade 3
      toxicity after radiotherapy. The frequency of secondary T790M mutation and
      subsequent Osimertinib exposure were similar in both groups. CONCLUSION:
      Radiotherapy may effectively extend EGFR TKI therapy for patients with
      oligoprogression on TKI. Improved PFS and overall survival were observed,
      although potential biases should not be overlooked. Further randomised studies
      are warranted.

PMID- 28499793
TI  - Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery
      system intended for the treatment of bacterial infections in cystic fibrosis.
AB  - Treatment of bacterial airway infections is essential for cystic fibrosis
      therapy. However, effectiveness of antibacterial treatment is limited as bacteria
      inside the mucus are protected from antibiotics and immune response. To overcome
      this biological barrier, ciprofloxacin was loaded into lipid-core nanocapsules
      (LNC) for high mucus permeability, sustained release and antibacterial activity.
      Ciprofloxacin-loaded LNC with a mean size of 180nm showed a by 50% increased drug
      permeation through mucus. In bacterial growth assays, the drug in the LNC had
      similar minimum inhibitory concentrations as the free drug in P. aeruginosa and
      S. aureus. Interestingly, formation of biofilm-like aggregates, which were
      observed for S. aureus treated with free ciprofloxacin, was avoided by exposure
      to LNC. With the combined advantages over the non-encapsulated drug,
      ciprofloxacin-loaded LNC represent a promising drug delivery system with the
      prospect of an improved antibiotic therapy in cystic fibrosis.

PMID- 28499794
TI  - On the role of forces governing particulate interactions in pharmaceutical
      systems: A review.
AB  - Process understanding for designing, optimizing and scaling of pharmaceutical
      unit operations is fundamentally important to address concerns of high risks,
      monumental costs, and productivity decline in the pharmaceutical industry. This
      is especially important in the rapidly changing landscape of the pharmaceutical
      industry. Pharmaceutical processes majorly deal with multiphase, multicomponent
      flows, basics of which are discussed in terms of fundamental contact and non
      contact forces. Also, basics of multiphase flow regimes, powder flow, and
      pertinent process modeling techniques relevant to pharmaceutical unit operations
      are discussed. The most fundamental contact and non-contact forces are then
      reviewed in detail on their molecular or physical origin, factors which influence
      these forces, numerical formalisms and modeling strategies to simulate flows and
      processes of pharmaceutical interest.

PMID- 28499796
TI  - The antenatal urinary tract dilation classification system accurately predicts
      severity of kidney and urinary tract abnormalities.
AB  - BACKGROUND: Urinary tract dilation (UTD) is a commonly diagnosed prenatal
      condition; however, it is currently unknown which features lead to benign and
      resolving or pathologic abnormalities. A consensus UTD classification system
      (antenatal UTD classification, UTD-A) was created by Nguyen et al. in 2014 [1],
      but has not yet been validated. OBJECTIVE: To evaluate the ability of the UTD-A
      system to identify kidney and urinary tract (KUT) abnormalities, assess whether
      UTD-A can predict severity of KUT conditions, and perform a cost analysis of
      screening ultrasound (US). METHODS: A retrospective single-center study was
      conducted at an academic medical center. Inclusion criteria were: neonates in the
      well or sick nursery who had a complete abdominal or limited renal US performed
      in the first 30 days of life between January 01, 2011 and December 31, 2013. Data
      were collected on prenatal US characteristics from which UTD-A classification was
      retrospectively applied, and postnatal data were collected up to 2 years
      following birth. RESULTS: A total of 203 patients were identified. Of the 36
      abnormal postnatal KUT diagnoses, 90% were identified prenatally as UTD A1 or UTD
      A2-3. The remaining 10% developed postnatal KUT abnormalities due to
      myelomeningocele, such as VUR or UTD, which were not evident prenatally. Overall
      sensitivity and specificity of the UTD-A system was 0.767 (95% CI 0.577, 0.901)
      and 0.836 (95% CI 0.758, 0.897), respectively, when resolved UTD was counted as a
      normal diagnosis. Postnatal diagnoses differed by UTD-A classification as shown
      in the Summary fig. Of all the obstructive uropathies, 90.9% occurred in the UTD
      A2-3 class and none occurred in UTD-A Normal. Rate of postnatally resolved UTD
      was significantly higher in the UTD A1 group (78%) compared with UTD A2-3 (31%)
      or UTD-A Normal (12%, all P < 0.001). There was a notable trend towards more UT
      surgeries, UTI, and positive VUR among UTD A2-3 patients, but statistical
      significance was limited by a small number of patients. CONCLUSIONS: This study
      found that the UTD-A classification system revealed important differences in the
      severity of UTD abnormalities. With repeated validation in larger cohorts, the
      UTD-A classification may be used to offer a prognosis for parents regarding
      prenatally diagnosed KUT conditions. Larger prospective studies should be
      designed to validate whether the UTD-A system can predict postnatal events
      related to UTD morbidity such as need for UT-related surgery or UTI.

PMID- 28499795
TI  - Anesthesia-inducing drugs also induce conditioned taste aversions.
AB  - Animals learn to reduce their intake of a tastant when its ingestion is followed
      by the administration of an anesthesia-inducing drug. To determine the nature of
      this intake suppression, the current study examined whether ketamine/xylazine
      (Experiment 1) and pentobarbital (Experiment 2) also conditionally reduce taste
      palatability. Using lick pattern analysis, we found that pairing saccharin with
      either drug reduced total licks, lick cluster size, and initial lick rate. Given
      that both lick cluster size and initial lick rate are indices of palatability,
      this pattern of results indicates that anesthesia-inducing drugs also induce
      conditioned taste aversions.

PMID- 28499797
TI  - The S.An.A.(r) concept: Semi-aerobic, Anaerobic, Aerated bioreactor landfill.
AB  - Hybrid Bioreactor Landfills are designed to enhance and speed up biological
      processes, aiming at reducing the duration of post operational phase until
      landfill completion. S.An.A.(r) (Semi-aerobic, Anaerobic, Aerated) concept
      consists in a Hybrid Bioreactor featuring a first semi-aerobic phase to enhance
      the methane production occurring in the following anaerobic step and a forced
      aeration for the abatement of the residual emissions. At the end of the last
      step, semi-aerobic conditions are restored and flushing applied for leaching
      residual non-biodegradable compounds. Results of the application of S.An.A.(r)
      concept to a lab scale bioreactor system showed that pre-aeration was effective
      in controlling the concentration of VFA, increasing pH and stimulating methane
      production during anaerobic phase; in particular with intermittent airflow the
      methane potential was 50% higher respect to control reactors. Forced aeration
      reduced organic compounds and nitrogen concentration in leachate of an order of
      magnitude, better performing in low airflow reactors. S.An.A.(r) Hybrid
      bioreactors proved to be an efficient system both for increasing methane
      production and reaching landfill completion in shorter time, suggesting that with
      proper landfill management, the duration of post-closure care might be reduced by
      25-35%.

PMID- 28499798
TI  - Pilot trial on separation conditions for diaper recycling.
AB  - By utilizing laboratory-scale tests, the optimal separation conditions for diaper
      recycling were identified, and then, these conditions were validated by a pilot
      trial. In this research, we determined the mass balances derived during various
      processing steps and identified the most feasible procedures to use for
      separating each material in the output flow. The results showed that drum
      screening was not able to remove all the fiber and super absorbent particles
      (SAP) in the plastic-rich fraction and that cellulose enzyme treatment can be a
      good solution. To achieve better separation of fibers and SAP, slot screening
      followed by a cleaner is a potential option. A feasible diaper recycling process
      was recommended based on these results. This process involves screening and
      enzymatic treatment for the plastic fraction, and screening, cleaning, and
      thickening for the fiber fraction. Treatment procedures were also proposed for
      the SAP fraction and rejected materials.

PMID- 28499799
TI  - Mouse<->rat aggregation chimaeras can develop to adulthood.
AB  - In order to examine interactions between cells originating from different species
      during embryonic development we constructed interspecific mouse<->rat chimaeras
      by aggregation of 8-cell embryos. Embryos of both species expressed different
      fluorescent markers (eGFP and DsRed), which enabled us to follow the fate of both
      components from the moment of aggregation until adulthood. We revealed that in
      majority of embryos the blastocyst cavity appeared inside the group of rat cells,
      while the mouse component was allocated to the deeper layer of the inner cell
      mass and to the polar trophectoderm. However, due to rearrangement of all cells
      and selective elimination of rat cells, shortly before implantation all primary
      lineages became chimaeric. Moreover, despite the fact that rat cells were always
      present in the mural trophectoderm, majority of mouse<->rat chimaeric blastocysts
      implanted in mouse uterus, and out of those 46% developed into foetuses and pups,
      half of which were chimaeric. In contrast to mural trophectoderm, polar
      trophectoderm derivatives, i.e. the placentae of all chimaeras were exclusively
      of mouse origin. This strongly suggests that the successful postimplantation
      development of chimaeras is enabled by gradual elimination of xenogeneic cells
      from the nascent placenta. The size of chimaeric newborns was within the limits
      of control mouse neonates. The rat component located preferentially in the
      anterior part of the body, where it contributed mainly to the neural tube. Our
      observations indicate that although chimaeric animals were able to reach
      adulthood, high contribution of rat cells tended to diminish their viability.

PMID- 28499800
TI  - Improving clinical laboratory performance through quality indicators.

PMID- 28499801
TI  - The effect of admission serum potassium levels on in-hospital and long-term
      mortality in type A acute aortic dissection.
AB  - BACKGROUND: Mild fluctuations in serum potassium (K+) levels are related to the
      prognosis of cardiovascular disease. This study aimed to determine the effect of
      admission serum potassium levels on in-hospital and long-term mortality in
      patients with Stanford type A acute aortic dissection (AAD). MATERIALS AND
      METHODS: A total of 588 consecutive patients with type A AAD were enrolled, and
      they were grouped according to admission serum potassium level: <3.5, 3.5 to
      <4.0, 4.0 to <4.5, 4.5 to <5.0, and >=5.0mmol/L. Clinical outcomes were in
      hospital death and long-term all-cause mortality. RESULTS: The in-hospital and
      long-term all-cause mortality rates were 10.7% and 16.3%, respectively. A U
      shaped relationship was observed between admission serum potassium levels and
      both in-hospital death and long-term mortality. Univariate Cox regression
      identified potassium levels outside the interval of <3.5 to 4.5mmol/L to be a
      risk factor for both in-hospital and long-term death. After adjusting for age,
      gender, surgery and other risk factors, potassium levels outside the interval of
      <3.5 to 4.5mmol/L still had a significant association with long-term death
      [hazard ratio (HR)=1.72, 95% confidence interval (95% CI): 1.07-2.74, P=0.024].
      Surgical intervention was the main protective factor associated with both in
      hospital (HR=0.01, 95% CI 0.01-0.06, P<0.001) and long-term survival (HR=0.06,
      95% CI 0.03-0.12, P<0.001). CONCLUSIONS: Among patients with Stanford type A AAD,
      admission serum potassium levels other than 3.5 to 4.5mmol/L might be associated
      with an increased risk of in-hospital death and long-term mortality.

PMID- 28499802
TI  - AMPK activates FOXO3a and promotes neuronal apoptosis in the developing rat brain
      during the early phase after hypoxia-ischemia.
AB  - AMP-activated protein kinase (AMPK) is a key metabolic and stress
      sensor/effector. Few investigations have been performed to study the role of AMPK
      in developing rat brain with hypoxia-ischemia (HI). Forkhead transcriptional
      factor (FOXO3a) has been revealed to be a critical effector of AMPK-mediated
      celluar apoptosis. However, it is not clear whether AMPK/FOXO3a pathway is
      involved in neuronal apoptosis in the developing rat brain after HI. In this
      study, we generated hypoxia-ischemia brain damage (HIBD) model using postnatal
      day 7 rats. We found that activation of AMPK was accompanied by the decrease of p
      mTOR, p-Akt and p-FOXO3a, which induced FOXO3a translocation into the nucleus and
      up-regulated the expression of Bim and cleaved caspase 3 (CC3). Furthermore, we
      discovered that AMPK inhibition by Compound C, a selective inhibitor for AMPK
      activity, significantly increased the phosphorylation levels of mTOR, Akt and
      FOXO3a, attenuated the nuclear translocation of FOXO3a, and inhibited Bim and CC3
      expression after HI. Moreover, AMPK inhibition reduced cellular apoptosis,
      attenuated brain infarct volume and promoted neurological recovery in the
      developing rat brain after HI. Our findings suggest that AMPK participates in the
      regulation of FOXO3a-mediated neuronal apoptosis in the developing rat brain
      after HI. Agents targeting AMPK may offer promise for rescuing neurons from HI
      induced damage.

PMID- 28499803
TI  - Establishment and characterization of primary astrocyte culture from adult mouse
      brain.
AB  - As a major class of glial cells, astrocytes have been indicated to play multi
      roles in physiological and pathological brain. Astrocyte cultures derived from
      postnatal mouse brains have been extensively used to characterize their
      biological properties. However, the inability to culture adult mouse primary
      astrocytes has long stymied studies of function in adult brain. Here, we
      developed a protocol to successfully establish highly enriched astrocyte cultures
      from the brains of adult mouse. Cortical tissues were collected to prepare cell
      suspension by enzymatic digestion and mechanical dissociation, and then plated
      onto vessels pre-coated with gelatin and matrigel and cultured in DMEM medium
      containing 20% fetal bovine serum (FBS). Forskolin (FSK) and glial-derived
      neurotrophic factor (GDNF) were use to promote astrocyte proliferation and
      survival respectively. These adult astrocyte cultures were identified by
      immunocytochemical, immunobloting and PCR analysis. Furthermore, biological and
      functional analysis indicated that they possess the biochemical and physiological
      properties of astrocytes, suggestive of a useful cell model for astroglial
      studies in adult brain.

PMID- 28499804
TI  - Monckeberg Arteriosclerosis: A Telltale Sign.
AB  - Monckeberg arteriosclerosis is often an incidental finding recognized at plain
      radiography. It differs from the more common atherosclerosis in that the tunica
      intima remains unaffected; hence, the vessel lumen is preserved. Monckeberg
      arteriosclerosis is most commonly seen in patients with diabetes and patients
      with end-stage renal disease. In this short communication, the author presents a
      rare case of Monckeberg arteriosclerosis affecting the facial vasculature.

PMID- 28499806
TI  - A Rare Sporadic Case of Camurati-Engelmann Disease With Jaw Involvement.
AB  - Camurati-Engelmann disease (CED), or progressive diaphyseal dysplasia, is an
      uncommon bone dysplasia that is inherited in an autosomal-dominant pattern. The
      disease mainly affects the diaphyses of the long bones but can induce sclerotic
      changes to the facial skeleton and skull base. The diagnosis of CED is based on
      clinical and radiologic features. This article presents the clinical and
      radiologic characteristics of the jaws as visualized on cone-beam computed
      tomograms of a 46-year-old woman diagnosed with CED.

PMID- 28499805
TI  - Differentiating 131I Radiation Sialadenitis From Autoimmune (Sjogren Syndrome)
      Sialadenitis: Case Report.
AB  - Radioactive iodine (131I) is used effectively for the treatment of differentiated
      thyroid cancers. Because it is actively secreted by the salivary glands,
      radiation damage to these glands can occur. Obstructive swellings after mealtime
      salivary stimulation are common occurrences. Dry mouth is not usually seen if low
      doses of 131I are used. A subjective complaint of xerostomia in a patient treated
      with 131I 75.8 mCi proved to be related to the simultaneous presence of Sjogren
      syndrome (SS). Serologic, histologic, scintigraphic, and salivary volume findings
      and the patient's subjective complaints served to establish the pre-existence of
      SS.

PMID- 28499807
TI  - Evaluation of insulin-like growth factor (IGF-1) and retinol binding protein (RBP
      4) levels in patients with newly diagnosed pancreatic adenocarcinoma (PDAC).
AB  - BACKGROUND/OBJECTIVES: The elevation of insulin-like growth factor 1 (IGF-1) and
      adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the
      risk of many cancers. The aim of this study was to evaluate the serum
      concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis
      (CP). METHODS: The study included 43 patients with PDAC, 39 patients with CP and
      10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA
      method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the
      Bioethics Committee at the Medical University of Lodz. RESULTS: In PDAC patients
      the serum IGF-1 level was significantly higher than in patients with CP (107.79
      +/- 66.40 ng/ml vs 89.91 +/- 74.06 ng/ml; P < 0.05). Patients with both CP and
      diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1
      compared with those who only had CP (51.33 +/- 24.30 ng/ml vs 108.42 +/- 82.39
      ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05
      +/- 32.44 ng/ml vs 98.79 +/- 79.47 ng/ml, P = 0.05). As regards the serum level
      of RBP-4, the PDAC and CP groups were not significantly different from each
      other. CONCLUSIONS: Diabetes accompanying PDAC does not influence the level of
      IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful
      for early diagnosis of PDAC. High concentration of RBP-4 is not specific to
      pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.

PMID- 28499808
TI  - High-contrast high-resolution imaging of posttraumatic mandibular nerve by 3DAC
      PROPELLER magnetic resonance imaging: correlation with the severity of sensory
      disturbance.
AB  - OBJECTIVE: Magnetic resonance neurography reveals abnormal morphologies of
      regenerated nerves and overgrown connective tissue in injured trigeminal nerves,
      suggesting neuroma formation. We hypothesized that such deformities and scar
      formation contribute to pain symptoms. STUDY DESIGN: High-contrast high
      resolution magnetic resonance imaging was utilized to evaluate the inferior
      alveolar nerve and lingual nerve following traumatic injury in 19 patients. The
      relationship between the morphologic classification and severity of the sensory
      disorder was assessed. RESULTS: In all cases, 3-dimensional anisotropy contrast
      periodically rotated overlapping parallel lines with enhanced reconstruction
      (3DAC-PROPELLER) successfully revealed the inner structures within the lesion.
      The isolated type represented the normal course of the nerve isolated from scar
      like tissue (8 cases), whereas the deformity type included the deformed nerve
      either within scar-like tissue or by itself, unassociated with surrounding scar
      like tissue (9 cases). In the remaining 2 cases, the nerve tissue and scar-like
      tissue were incorporated. Patients with the deformity type exhibited
      significantly more severe pain symptoms compared with patients with the isolated
      type. CONCLUSIONS: Overgrown connective tissue does not necessarily block
      regenerating nerves and itself may not cause pain. The morphologic findings on
      the 3DAC-PROPELLER were relevant to the severity of pain symptoms.

PMID- 28499810
TI  - Prevalence of late-onset pompe disease in Portuguese patients with diaphragmatic
      paralysis - DIPPER study.
AB  - : Pompe disease is a rare autosomal recessive neuromuscular disorder caused by
      acid alpha-glucosidase enzyme (GAA) deficiency and divided into two distinct
      variants, infantile- and late-onset. The late-onset variant is characterized by a
      spectrum of phenotypic variation that may range from asymptomatic, to reduced
      muscle strength and/or diaphragmatic paralysis. Since muscle strength loss is
      characteristic of several different conditions, which may also cause
      diaphragmatic paralysis, a protocol was created to search for the diagnosis of
      Pompe disease and exclude other possible causes. METHODS: We collected a sample
      size of 18 patients (10 females, 8 males) with a median age of 60 years and
      diagnosis of diaphragmatic paralysis of unknown etiology, followed in the
      Pulmonology outpatient consultation of 9 centers in Portugal, over a 24-month
      study period. We evaluated data from patient's clinical and demographic
      characteristics as well as complementary diagnostic tests including blood tests,
      imaging, neurophysiologic and respiratory function evaluation. All patients were
      evaluated for GAA activity with DBS (dried blood test) or serum quantification
      and positive results confirmed by serum quantification and sequencing. RESULTS:
      Three patients were diagnosed with Pompe's disease and recommended for enzyme
      replacement therapy. The prevalence of Pompe, a rare disease, in our
      diaphragmatic paralysis patient sample was 16.8%. CONCLUSION: We conclude that
      DBS test for GAA activity should be recommended for all patients with
      diaphragmatic paralysis which, despite looking at all the most common causes,
      remains of unknown etiology; this would improve both the timing and accuracy of
      diagnosis for Pompe disease in this patient population. Accurate diagnosis will
      lead to improved care for this rare, progressively debilitating but treatable
      neuromuscular disease.

PMID- 28499811
TI  - The effect of lever height on the microstructure of operant behavior.
AB  - The effect of lever height on the temporal organization of reinforced lever
      pressing was examined. Lever pressing was reinforced on a variable-interval 30-s
      schedule in rats, with lever height manipulated across six successive conditions.
      Parameters of the organization of responses in bouts (bout length distribution,
      bout-initiation rate, within-bout rate, and sequential dependency) were
      estimated. These estimates revealed (1) a qualitative change in the distribution
      of IRTs and their sequential dependency when the lever was too high, (2) a
      mixture of geometrically-distributed bout lengths at all lever heights, and (3)
      longer bouts at lower and intermediate lever heights. In accordance with previous
      data, these findings suggest that lower and intermediate lever heights favored
      lever pressing with longer bout lengths, faster bout initiation, faster within
      bout responding, and more sequentially dependent timing. These results underscore
      the disociability of motoric capacity in operant performance, and may reflect the
      influence of the body size on the temporal organization of the operant.

PMID- 28499809
TI  - An emerging role for the lateral habenula in aggressive behavior.
AB  - Inter-male aggression is an essential component of social behavior in organisms
      from insects to humans. However, when expressed inappropriately, aggression poses
      significant threats to the mental and physical health of both the aggressor and
      the target. Inappropriate aggression is a common feature of numerous
      neuropsychiatric disorders in humans and has been hypothesized to result from the
      atypical activation of reward circuitry in response to social targets. The
      lateral habenula (LHb) has recently been identified as a major node of the
      classical reward circuitry and inhibits the release of dopamine from the midbrain
      to signal negative valence. Here, we discuss the evidence linking LHb function to
      aggression and its valence, arguing that strong LHb outputs to the ventral
      tegmental area (VTA) and the dorsal raphe nucleus (DRN) are likely to play roles
      in aggression and its rewarding components. Future studies should aim to
      elucidate how various inputs and outputs of the LHb shape motivation and reward
      in the context of aggression.

PMID- 28499812
TI  - Modeling of the interaction between grip force and vibration transmissibility of
      a finger.
AB  - It is known that the vibration characteristics of the fingers and hand and the
      level of grip action interacts when operating a power tool. In the current study,
      we developed a hybrid finger model to simulate the vibrations of the hand-finger
      system when gripping a vibrating handle covered with soft materials. The hybrid
      finger model combines the characteristics of conventional finite element (FE)
      models, multi-body musculoskeletal models, and lumped mass models. The distal,
      middle, and proximal finger segments were constructed using FE models, the finger
      segments were connected via three flexible joint linkages (i.e., distal
      interphalangeal joint (DIP), proximal interphalangeal joint (PIP), and
      metacarpophalangeal (MCP) joint), and the MCP joint was connected to the ground
      and handle via lumped parameter elements. The effects of the active muscle forces
      were accounted for via the joint moments. The bone, nail, and hard connective
      tissues were assumed to be linearly elastic whereas the soft tissues, which
      include the skin and subcutaneous tissues, were considered as hyperelastic and
      viscoelastic. The general trends of the model predictions agree well with the
      previous experimental measurements in that the resonant frequency increased from
      proximal to the middle and to the distal finger segments for the same grip force,
      that the resonant frequency tends to increase with increasing grip force for the
      same finger segment, especially for the distal segment, and that the magnitude of
      vibration transmissibility tends to increase with increasing grip force,
      especially for the proximal segment. The advantage of the proposed model over the
      traditional vibration models is that it can predict the local vibration behavior
      of the finger to a tissue level, while taking into account the effects of the
      active musculoskeletal force, the effects of the contact conditions on
      vibrations, the global vibration characteristics.

PMID- 28499813
TI  - Red blood cell aggregate flux in a bifurcating microchannel.
AB  - Red blood cell aggregation plays a key role in microcirculatory flows, however,
      little is known about the transport characteristics of red blood cell aggregates
      in branching geometries. This work reports on the fluxes of red blood cell
      aggregates of various sizes in a T-shaped microchannel, aiming to clarify the
      effects of different flow conditions in the outlet branches of the channel. Image
      analysis techniques, were utilised, and moderately aggregating human red blood
      cell suspensions were tested in symmetric (~50-50%) and asymmetric flow splits
      through the two outlet (daughter) branches. The results revealed that the flux
      decreases with aggregate size in the inlet (parent) and daughter branches, mainly
      due to the fact that the number of larger structures is significantly smaller
      than that of smaller structures. However, when the flux in the daughter branches
      is examined relative to the aggregate size flux in the parent branch an increase
      with aggregate size is observed for a range of asymmetric flow splits. This
      increase is attributed to size distribution and local concentration changes in
      the daughter branches. The results show that the flow of larger aggregates is not
      suppressed downstream of a bifurcation, and that blood flow is maintained, for
      physiological levels of red blood cell aggregation.

PMID- 28499814
TI  - Selected cholesterol biosynthesis inhibitors produce accumulation of the
      intermediate FF-MAS that targets nucleus and activates LXRalpha in HepG2 cells.
AB  - Sterol intermediates of the cholesterol biosynthetic pathway have drawn attention
      for novel biological activities. Follicular fluid meiosis activating sterol (FF
      MAS) is a LXRalpha ligand and a potential modulator of physiologic processes
      regulated by nuclear receptors, such as lipid homeostasis and cell proliferation.
      In this work, we established a model to selectively accumulate FF-MAS in HepG2
      cells, by using a combination of the inhibitors AY9944 and 17-hydroxyprogesterone
      to block C14-sterol reductases and the downstream C4-demethylase complex. We
      investigated the effects produced by altered levels of cholesterol biosynthesis
      intermediates, in order to dissect their influence on LXRalpha signaling. In
      particular, endogenously accumulated FF-MAS was able to modulate the expression
      of key genes in cholesterol metabolism, to activate LXRalpha nuclear signaling
      resulting in increased lipogenesis, and to inhibit HepG2 cells proliferation.
      Moreover, a fluorescent ester derivative of FF-MAS localized in nuclear lipid
      droplets, suggesting a role for these organelles in the storage of signaling
      lipids interacting with nuclear partners.

PMID- 28499815
TI  - New insight into the interaction of TRAF2 C-terminal domain with lipid raft
      microdomains.
AB  - In this study we provide the first evidence of the interaction of a truncated
      TRAF2 with lipid raft microdomains. We have analyzed this interaction by
      measuring the diffusion coefficient of the protein in large and giant unilamellar
      vesicles (LUVs and GUVs, respectively) obtained both from synthetic lipid
      mixtures and from natural extracts. Steady-state fluorescence measurements
      performed with synthetic vesicles indicate that this truncated form of TRAF2
      displays a tighter binding to raft-like LUVs with respect to the control (POPC
      containing LUVs), and that this process depends on the protein oligomeric state.
      Generalized Polarization measurements and spectral phasor analysis revealed that
      truncated-TRAF2 affects the membrane fluidity, especially when vesicles are
      heated up at physiological temperature. The addition of nanomolar concentration
      of TRAF2 in GUVs also seems to exert a mechanical action, as demonstrated by the
      formation of intraluminal vesicles, a process in which ganglioside GM1 plays a
      crucial role.

PMID- 28499816
TI  - Tumor ablation using low-intensity ultrasound and sound excitable drug.
AB  - The cell membrane is a semi-fluid container that defines the boundary of cells,
      and provides an enclosed environment for vital biological processes. A sound
      excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the
      plasma membrane under gentle ultrasound insonation, 1MHz, 1W/cm2. The frequency
      and power density of insonation are within the physical therapy and medical
      imaging windows; thus the applied ultrasound is safe and not harmful to tissues.
      The insertion of SEDs into the plasma membrane is not toxic to cells; however,
      the intruding SEDs weaken the membrane's integrity. Under insonation, the
      ultrasound energy destabilized the SED disrupted membranes, resulting in membrane
      rupture and eventual cell death. In a xenograft breast tumor model, the SED alone
      or the ultrasound alone caused little adverse effects to tumor tissue, while the
      combined treatment triggered necrosis with a brief local insonation of 3min. The
      described sono-membrane rupture therapy could be a safe alternative to the
      currently used high-energy tissue ablation technology, which uses X-rays, gamma
      rays, electron beams, protons, or high-intensity focused ultrasound.

PMID- 28499817
TI  - Use of CellNetAnalyzer in biotechnology and metabolic engineering.
AB  - Mathematical models of the cellular metabolism have become an essential tool for
      the optimization of biotechnological processes. They help to obtain a systemic
      understanding of the metabolic processes in the used microorganisms and to find
      suitable genetic modifications maximizing the production performance. In
      particular, methods of stoichiometric and constraint-based modeling are
      frequently used in the context of metabolic and bioprocess engineering. Since
      metabolic networks can be complex and comprise hundreds or even thousands of
      metabolites and reactions, dedicated software tools are required for an efficient
      analysis. One such software suite is CellNetAnalyzer, a MATLAB package providing,
      among others, various methods for analyzing stoichiometric and constraint-based
      metabolic models. CellNetAnalyzer can be used via command-line based operations
      or via a graphical user interface with embedded network visualizations. Herein we
      will present key functionalities of CellNetAnalyzer for applications in
      biotechnology and metabolic engineering and thereby review constraint-based
      modeling techniques such as metabolic flux analysis, flux balance analysis, flux
      variability analysis, metabolic pathway analysis (elementary flux modes) and
      methods for computational strain design.

PMID- 28499818
TI  - Biosurfactant-biopolymer driven microbial enhanced oil recovery (MEOR) and its
      optimization by an ANN-GA hybrid technique.
AB  - A lipopeptide biosurfactant produced by marine Bacillus megaterium and a
      biopolymer produced by thermophilic Bacillus licheniformis were tested for their
      application potential in the enhanced oil recovery. The crude biosurfactant
      obtained after acid precipitation effectively reduced the surface tension of
      deionized water from 70.5 to 28.25mN/m and the interfacial tension between lube
      oil and water from 18.6 to 1.5mN/m at a concentration of 250mgL-1. The
      biosurfactant exhibited a maximum emulsification activity (E24) of 81.66% against
      lube oil. The lipopeptide micelles were stabilized by addition of Ca2+ ions to
      the biosurfactant solution. The oil recovery efficiency of Ca2+ conditioned
      lipopeptide solution from a sand-packed column was optimized by using artificial
      neural network (ANN) modelling coupled with genetic algorithm (GA) optimization.
      Three important parameters namely lipopeptide concentration, Ca2+ concentration
      and solution pH were considered for optimization studies. In order to further
      improve the recovery efficiency, a water soluble biopolymer produced by Bacillus
      licheniformis was used as a flooding agent after biosurfactant incubation. Upon
      ANN-GA optimization, 45% tertiary oil recovery was achieved, when biopolymer at a
      concentration of 3gL-1 was used as a flooding agent. Oil recovery was only 29% at
      optimal conditions predicted by ANN-GA, when only water was used as flooding
      solution. The important characteristics of biopolymers such as its viscosity,
      pore plugging capabilities and bio-cementing ability have also been tested. Thus,
      as a result of biosurfactant incubation and biopolymer flooding under the optimal
      process conditions, a maximum oil recovery of 45% was achieved. Therefore, this
      study is novel, timely and interesting for it showed the combined influence of
      biosurfactant and biopolymer on solubilisation and mobilization of oil from the
      soil.

PMID- 28499819
TI  - Correction to Lancet Glob Health 2017; published online April 30,
      http://dx.doi.org/10.1016/S2214-109X(17)30196-1.

PMID- 28499820
TI  - HE4 expression in lung cancer, a meta-analysis.
AB  - BACKGROUND: The prognostic role of Human epididymis protein 4 (HE4) expression in
      lung cancer remains controversial. We performed this meta-analysis to assess the
      prognostic value of HE4 expression in lung cancer. METHODS: A systematic
      literature search was conducted to identify eligible studies in PubMed, Embase
      and Wanfang databases. The pooled hazard ratios (HRs) and their 95% confidence
      intervals (CIs) were used to assess the relationship. RESULTS: A total of 1412
      patients from 8 studies were included in this meta-analysis. The results of
      univariate analysis (HR=1.73, 95% CI: 1.19-2.52, P=0.004) and multivariate
      analysis (HR=2.49, 95% CI: 1.89-3.28, P<0.001) demonstrated that high HE4
      expression in lung cancer patients was correlated with poor overall survival
      (OS). We observed through further stratified analysis of the results of the
      univariate analysis that high HE4 expression was associated with worse OS in
      Asian lung cancer patients (HR=2.48, 95% CI: 1.88-3.26, P<0.001). However, there
      was no significant association between high HE4 expression and poor OS in
      Caucasian patients (HR=1.12, 95% CI: 0.80-1.55, P=0.513). CONCLUSION: High serum
      HE4 level was a marker of poor prognosis in lung cancer patients, particularly in
      Asian patients with lung cancer.

PMID- 28499821
TI  - X-ray crystal structure of rivoglitazone bound to PPARgamma and PPAR subtype
      selectivity of TZDs.
AB  - Thiazolidinedione (TZD) compounds targeting the nuclear receptor peroxisome
      proliferator-activated receptor gamma (PPARgamma) demonstrate unique benefits for
      the treatment of insulin resistance and type II diabetes. TZDs include
      rosiglitazone, pioglitazone and rivoglitazone, with the latter being the most
      potent. The TZDs are only marginally selective for the therapeutic target
      PPARgamma as they also activate PPARalpha and PPARdelta homologues to varying
      degrees, causing off-target effects. While crystal structures for TZD compounds
      in complex with PPARgamma are available, minimal structural information is
      available for TZDs bound to PPARalpha and PPARdelta. This paucity of structural
      information has hampered the determination of precise structural mechanisms
      involved in TZD selectivity between PPARs. To help address these questions
      molecular dynamic simulations were performed of rosiglitazone, pioglitazone and
      rivoglitazone in complex with PPARalpha, PPARdelta, and PPARgamma in order to
      better understand the mechanisms of PPAR selectivity. The simulations revealed
      that TZD interactions with residues Tyr314 and Phe318 of PPARalpha and residues
      Phe291 and Thr253 of PPARdelta as well as the omega loop, are key determinants of
      TZD receptor selectivity. Notably, in this study, we solve the first X-ray
      crystal structure of rivoglitazone bound to any PPAR. Rivoglitazone forms a
      unique hydrogen bond network with the residues of the PPARgamma co-activator
      binding surface (known as AF2) and makes more extensive contacts with helix 3 and
      the beta-sheet as compared to model TZD compounds such as rosiglitazone.

PMID- 28499822
TI  - Activation of STAT3/HIF-1alpha/Hes-1 axis promotes trastuzumab resistance in HER2
      overexpressing breast cancer cells via down-regulation of PTEN.
AB  - BACKGROUND: Resistance to the HER2-targeted antibody trastuzumab remains to be a
      major clinical challenge in the treatment of HER2-positive breast cancer. Hyper
      activation of STAT3 is proposed to be a predictive biomarker of trastuzumab
      resistance. However, the precise mechanism(s) remains poorly defined. Evidence is
      emerging that HIF-1alpha, a central downstream element of STAT3 pathway, serves a
      pivotal role in the complex signaling network with subsequent diverse cellular
      events. MATERIAL AND METHODS: We have established trastuzumab resistant SKBR3
      cells (SKBR3-TR). The cell viability, apoptosis as well as western blot, siRNA
      transfection and co-immunoprecipitation assays were performed to evaluate the
      involvement of STAT3/HIF-1alpha in modulation of trastuzumab resistance. RESULTS:
      We found that in SKBR3-TR cells and conditioned medium-treated parental cells,
      constitutive phosphorylated STAT3 coincided with prominent up-regulation of HIF
      1alpha which was accompanied with PTEN attenuation. Moreover, the inhibition of
      STAT3 activation by Stattic and/or genetically STAT3 knocking down decreased HIF
      1alpha level in SKBR3-TR cells. Additionally, treatment with Stattic and/or STAT3
      siRNA engendered the up-regulation of PTEN protein in STAT3-inhibited resistant
      cells. Restoration of PTEN was also observed following siRNA-mediated silencing
      of HIF-1alpha expression. Moreover, down-regulation of HIF-1alpha caused a
      reduction in the HES-1 content. Further study with HES-1 specific siRNA revealed
      the elevation of PTEN expression in HES-1 knock-down trastuzumab resistant cells.
      CONCLUSION: The impairment of STAT3-HIF-1alpha-HES-1 pathway restored trastuzumab
      sensitivity through up-regulation of PTEN protein. GENERAL SIGNIFICANCE: These
      findings highlighted the signal integrator role of HIF-1alpha in STAT3-mediated
      trastuzumab resistance induction which would be valuable in designing more
      efficient chemosensitization strategies.

PMID- 28499823
TI  - Structural and mechanistic insights into Mycothiol Disulphide Reductase and the
      Mycoredoxin-1-alkylhydroperoxide reductase E assembly of Mycobacterium
      tuberculosis.
AB  - Mycobacteria employ a versatile machinery of the mycothiol-dependent system,
      containing the proteins mycothiol disulfide reductase (Mtr), the oxido-reductase
      Mycoredoxin-1 (Mrx-1) and the alkyl-hydroperoxide subunit E (AhpE). The mycothiol
      dependent protein ensemble regulates the balance of oxidized-reduced mycothiol,
      to ensure a reductive intracellular environment for optimal functioning of its
      proteins even upon exposure to oxidative stress. Here, we determined the first
      low-resolution solution structure of Mycobacterium tuberculosis Mtr (MtMtr)
      derived from small-angle X-ray scattering data, which provides insight into its
      dimeric state. The solution shape reveals the two NADPH-binding domains inside
      the dimeric MtMtr in different conformations. NMR-titration shows that the MtMtr
      MtMrx-1 interaction is characterized by a fast exchange regime and critical
      residues involved in the protein-protein interaction were identified. Using NMR
      spectroscopy and docking studies, the epitopes of MtMrx-1 and MtAhpE interaction
      are described, shedding new light into the interaction interface and mechanism of
      action. Finally, the essential residue of MtMrx-1 identified in the interaction
      with MtMtr and MtAhpE form a platform for structure-guided drug design against
      the versatile enzyme machinery of the mycothiol-dependent system inside M.
      tuberculosis.

PMID- 28499824
TI  - Quantifying dietary exposure to pesticide residues using spraying journal data.
AB  - Relatively few studies are available on the combined risk of realistic dietary
      pesticide exposure. Despite available studies showing low risk, public concern
      remains. Recent methods used to estimate realistic exposure levels have a number
      of drawbacks, and better methods are needed. Using a novel approach, we estimated
      the combined exposure in the Danish population, resulting from pesticide usage in
      Danish agriculture. The complete Danish spraying journal data from 2014, and
      supervised trial residue levels reported by EFSA, were used in combination,
      generating residue estimates in 25 crops. Cumulative risk assessments were made
      for six typical Danish consumer diets. In terms of intake of cereals, sugar,
      fruits and vegetables, the 25 crops included accounted 70% of the diets of Danish
      consumers. The Hazard Index (HI) method was used to assess the consumer risk.
      Despite the conservative (cautious) approach, low HI values where obtained.
      Highest HI was 14% of the Acceptable Daily Intake (ADI) for Children. The main
      advantages of the new exposure estimation method are 1) comprehensive use data
      not relying on random samples, 2) coverage of all pesticides used, and 3) more
      precise estimates of residues that are below the standard reporting limits in the
      national monitoring program.

PMID- 28499825
TI  - Induction of cytochrome P450-dependent mixed function oxidase activities and
      peroxisome proliferation by chloramine-T in male rat liver.
AB  - Chloramine-T is an antimicrobial agent recognized for its disinfectant properties
      widely used in food industry. As an N-chloro-compound, chloramine-T contains
      electrophilic chlorine and in water it hydrolyses to hypochlorite. Chlorine as
      hypochlorous acid or hypochlorite is a very reactive chemical which can function
      as both an oxidant and halogenating agent. Because chloramine-T could be involved
      in the metabolic activation of drugs, in the present study the effects of
      chloramine-T on the activities of some drug metabolizing enzymes in rat liver
      microsomes and peroxisome proliferation were determined in vivo. Rats were
      treated orally with chloramine-T at doses of 1.25, 2.50, 5 and 10 mg/kg body
      weight (bw)/day for 6 days. The activities of CYP2E1, CYP1A1/2 CYP2B1/2, CYP3A4
      and CYP4A1/2 enzymes significantly increased after treatment with 2.50, 5 and 10
      mg/kg bw/day, in a dose-dependent manner as compared to control. This effect was
      not observed after chloramine-T treatment at dose of 1.25 mg/kg bw/day. Our
      results suggest that chloramine-T may potentiate the toxicity of many xenobiotics
      via metabolic activation and/or accumulation of reactive metabolites.

PMID- 28499826
TI  - RIFM fragrance ingredient safety assessment, 5-Acetyl-3-isopropyl-1,1,2,6
      tetramethylindane, CAS Registry Number 68140-48-7.

PMID- 28499827
TI  - Drug-resistant tuberculosis threatens WHO's End-TB strategy.

PMID- 28499829
TI  - Characteristics of traditional Chinese medicine usage in children with precocious
      puberty: A nationwide population-based study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Precocious puberty (PP) occurs in children with
      the early onset of pubertal development leading to physical and psychological
      problems. Current medical treatment is expensive and has its side effects.
      However, little is known about the utilization of traditional Chinese medicine
      (TCM) among patients with PP. To characterize the application of TCM among these
      patients, we conducted a nationwide population-based study. MATERIALS AND
      METHODS: We used the Taiwanese National Health Insurance Research Database
      (NHIRD), to perform a nationwide population-based study. The NHIRD has a derived
      dataset with the information for a randomly selected half of all insured children
      from 1997 to 2008 in Taiwan. We identified children <18 years of age with newly
      diagnosed sexual precocity (ICD-9 CM code: 259.1). The subjects were categorized
      based on the inclusion of TCM in their treatment plan. RESULTS: Overall, 3495
      newly diagnosed subjects with sexual precocity were included. Among these
      children, 1.86% (N=65) had used TCM. There were significantly more subjects with
      no treatment, 87.32% (N=3052), than those with treatment of TCM, western
      medicine, or both. Most of the TCM users received Chinese herbal remedies
      (98.25%), and only 1.75% received acupuncture or manipulative therapies. Zhi-Bai
      Di-Huang-Wan was the most frequently prescribed TCM formulation (23.73%), while
      Mai-Ya (Fructus Hordei Germinatus) was the most commonly prescribed single herb
      (10.87%). CONCLUSION: Our study identified the characteristics and prescription
      patterns of TCM for children with PP in Taiwan. Further basic mechanistic studies
      and clinical trials are needed to confirm the efficacy and mechanism.

PMID- 28499828
TI  - Estimating the future burden of multidrug-resistant and extensively drug
      resistant tuberculosis in India, the Philippines, Russia, and South Africa: a
      mathematical modelling study.
AB  - BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR)
      tuberculosis are emerging worldwide. The Green Light Committee initiative
      supported programmatic management of drug-resistant tuberculosis in 90 countries.
      We used estimates from the Preserving Effective TB Treatment Study to predict MDR
      and XDR tuberculosis trends in four countries with a high burden of MDR
      tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We
      calibrated a compartmental model to data from drug resistance surveys and WHO
      tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis
      and the percentage of incident MDR and XDR tuberculosis caused by acquired drug
      resistance, assuming no fitness cost of resistance from 2000 to 2040 in India,
      the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the
      percentage of MDR tuberculosis among incident cases of tuberculosis to increase,
      reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in
      the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa
      in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR
      tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in
      India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5%
      (2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less
      than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance
      caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease
      to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast
      to increase in all four countries despite improvements in acquired drug
      resistance shown by the Green Light Committee-supported programmatic management
      of drug-resistant tuberculosis. Additional control efforts beyond improving
      acquired drug resistance rates are needed to stop the spread of MDR and XDR
      tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US
      Agency for International Development and US Centers for Disease Control and
      Prevention, Division of Tuberculosis Elimination.

PMID- 28499830
TI  - Implementation of a systematic culturing program to monitor the efficacy of
      endoscope reprocessing: outcomes and costs.
AB  - BACKGROUND AND AIMS: In 2015, the U.S. Food and Drug Administration and Centers
      for Disease Control and Prevention (CDC) issued guidance for duodenoscope
      culturing and reprocessing in response to outbreaks of carbapenem-resistant
      Enterobacteriaceae (CRE) duodenoscope-related infections. Based on this guidance,
      we implemented best practices for reprocessing and developed a systematic process
      for culturing endoscopes with elevator levers. The aim of this study is to report
      the outcomes and direct costs of this program. METHODS: First, clinical
      microbiology data from 2011 to 2014 were reviewed retrospectively to assess for
      possible elevator lever-equipped endoscope-related CRE infections. Second, a
      program to systematically culture elevator lever-equipped endoscopes was
      implemented. Each week, about 25% of the inventory of elevator lever-equipped
      endoscopes is cultured based on the CDC guidelines. If any cultures return
      bacterial growth, the endoscope is quarantined pending repeat culturing. The
      costs of the program, including staff time and supplies, have been calculated.
      RESULTS: From 2011 to 2014, none of 17 patients with documented CRE infection had
      undergone ERCP or endoscopic ultrasound in the previous 36 months. From June 2015
      to September 2016, 285 cultures were performed. Three (1.1%) had bacterial
      growth, 2 with skin contaminants and 1 with an oral contaminant. The associated
      endoscopes were quarantined and reprocessed, and repeat cultures were negative.
      The total estimated cost of our program for an inventory of 20 elevator lever
      equipped endoscopes was $30,429.60 per year ($1521.48 per endoscope).
      CONCLUSIONS: This 16-month evaluation of a systematic endoscope culturing program
      identified a low rate of positive cultures after elevator lever endoscope
      reprocessing. All positive cultures were with non-enteric microorganisms. The
      program was of modest cost and identified reprocessing procedures that may have
      led to a low rate of positive cultures.

PMID- 28499831
TI  - Resolution of hypertropia with correction of consecutive horizontal deviation.
AB  - BACKGROUND: To study the resolution of hypertropia in patients who undergo
      horizontal deviation surgery for consecutive esotropia or consecutive exotropia.
      METHODS: We retrospectively reviewed the records of 23 patients with consecutive
      esotropia or exotropia who had concomitant vertical tropia. All patients had had
      surgery for horizontal deviation that required further surgery to correct
      consecutive horizontal strabismus and had a minimum of six months of
      postoperative follow-up. All patients were noted to have vertical deviation
      greater than 5 prism diopters (PD) in primary position on preoperative
      examination. Patients underwent corrective surgery for horizontal strabismus
      without surgical manipulation of the vertical extraocular muscles. The exclusion
      criteria were coexisting oblique muscle dysfunction, manifest or latent
      dissociated vertical deviation, and extraocular muscle palsy. RESULTS: The mean
      preoperative vertical deviations were 7.6 +/- 2.3 PD for distance and 7.3 +/- 2.3
      PD for near. All patients had resolution of vertical deviation in all fields of
      gaze despite surgical correction only being made to horizontal extraocular
      muscles. No patients had measureable vertical tropia during six months of follow
      up. CONCLUSION: We propose that measureable hypertropia unrelated to oblique
      muscle dysfunction, dissociated vertical deviation, or paretic/mechanical muscle
      that coincides with consecutive horizontal deviation can be resolved with
      horizontal muscle surgery alone. Therefore, it may not be necessary to perform
      vertical surgery to correct coincident vertical deviation in patients with
      consecutive horizontal deviation. More research is needed in the form of
      prospective clinical trials to determine whether vertical surgery has any utility
      for these patients.

PMID- 28499832
TI  - Versatile and precise gene-targeting strategies for functional studies in
      mammalian cell lines.
AB  - The advent of programmable nucleases such as ZFNs, TALENs and CRISPR/Cas9 has
      brought the power of genetic manipulation to widely used model systems. In
      mammalian cells, nuclease-mediated DNA double strand break is mainly repaired
      through the error-prone non-homologous end-joining (NHEJ) repair pathway,
      eventually leading to accumulation of small deletions or insertions (indels) that
      can inactivate gene function. However, due to the variable size of the indels and
      the polyploid status of many cell lines (e.g., cancer-derived cells), obtaining a
      knockout usually requires lengthy screening and characterization procedures.
      Given the more precise type of modifications that can be introduced upon homology
      directed repair (HDR), we have developed HDR-based gene-targeting strategies that
      greatly facilitate the process of knockout generation in cell lines. To generate
      reversible knockouts (R-KO), a selectable promoter-less STOP cassette is inserted
      in an intron, interrupting transcription. Loss-of-function can be validated by RT
      qPCR and is removable, enabling subsequent restoration of gene function. A
      variant of the R-KO procedure can be used to introduce point mutations. To
      generate constitutive knockouts (C-KO), an exon is targeted, which makes use of
      HDR-based gene disruption together with NHEJ-induced indels on non-HDR targeted
      allele(s). Hence the C-KO procedure greatly facilitates simultaneous inactivation
      of multiple alleles. Overall these genome-editing tools offer superior precision
      and efficiency for functional genetic approaches. We provide detailed protocols
      guiding in the design of targeting vectors and in the analysis and validation of
      gene targeting experiments.

PMID- 28499835
TI  - Increase of reactive oxygen species generation in cerebral cortex slices after
      the transiently enhanced metabolic activity.
AB  - Under certain conditions such as hypoxia-reoxygenation, the generation of
      reactive oxygen species (ROS) increases following hypoxia caused by a decreased
      oxygen supply. As another hypoxic condition, an excess neural activity status
      including epileptic seizure induces a decrease in tissue oxygen partial pressure
      (pO2) caused by enhanced oxygen utilization; however, whether ROS generation
      increases following the hypoxic status induced by transiently enhanced energy
      metabolism in brain tissue currently remains unknown. We herein investigated ROS
      dependent chemiluminescence in cerebral cortex slices during the restoration of
      transiently enhanced energy metabolism induced by a high-potassium treatment with
      tissue pO2 changes and redox balance. ROS generation in the tissue was enhanced
      after high-potassium-induced hypoxia, but not by the reversed order of the
      treatment: control-potassium then high-potassium treatment, high-potassium
      treatment alone, and control-potassium treatment alone. The high-potassium
      treatment induced a transient decrease in tissue pO2 and a shift in the tissue
      redox balance towards reduction. The transient shift in the tissue redox balance
      towards reduction with enhanced metabolic activity and its recovery may correlate
      with ROS generation. This phenomenon may mimic ROS generation following the
      hypoxic status induced by transiently enhanced energy metabolism.

PMID- 28499833
TI  - Mitochondrial dysfunction in cancer: Potential roles of ATF5 and the
      mitochondrial UPR.
AB  - Mitochondria form a cellular network of organelles, or cellular compartments,
      that efficiently couple nutrients to energy production in the form of ATP. As
      cancer cells rely heavily on glycolysis, historically mitochondria and the
      cellular pathways in place to maintain mitochondrial activities were thought to
      be more relevant to diseases observed in non-dividing cells such as muscles and
      neurons. However, more recently it has become clear that cancers rely heavily on
      mitochondrial activities including lipid, nucleotide and amino acid synthesis,
      suppression of mitochondria-mediated apoptosis as well as oxidative
      phosphorylation (OXPHOS) for growth and survival. Considering the variety of
      conditions and stresses that cancer cell mitochondria may incur such as hypoxia,
      reactive oxygen species and mitochondrial genome mutagenesis, we examine
      potential roles for a mitochondrial-protective transcriptional response known as
      the mitochondrial unfolded protein response (UPRmt) in cancer cell biology.

PMID- 28499834
TI  - N-stearoyltyrosine protects primary cortical neurons against oxygen-glucose
      deprivation-induced apoptosis through inhibiting anandamide inactivation system.
AB  - N-stearoylthrosine (NST), a synthesized anandamide (AEA) analogue, plays a
      neuroprotective role in neurodegenerative diseases and cerebrovascular diseases.
      Several studies have demonstrated that the endocannabinoids systems (ECS) are
      involved in the neuroprotective effects against cerebral ischemic injury. Oxygen
      glucose deprivation (OGD)-induced neuronal injury elevated the levels of
      endocannabinoids and activated ECS. This research was conducted to investigate
      the neuroprotective effect of NST against OGD-induced neuronal injury in cultured
      primary cortical neurons and the potential mechanism involved. Cortical neurons
      were treated with NST at indicate concentrations for 30min prior to injury and
      OGD injured neurons were incubated with normal conditions for 0-24h. The best
      neuroprotective effect of NST against OGD-induced injury occurred at 10MUM. All
      data indicated that the neuroprotective effect of NST against OGD-induced injury
      resulted from blocking anandamide membrane transporter (AMT) (IC50=11.74nM) and
      inhibiting fatty acid amide hydrolase activity (FAAH) (IC50=16.54nM). Our
      findings demonstrated that NST has an important role in cerebral ischemic injury
      pathological progression through activating cannabinoid receptors by inhibiting
      AEA inactivation system. These data suggested a potential role for NST in the
      therapeutic consideration of cerebral ischemic injury. However, inhibition of AEA
      inactivation system may provide a neuroprotective effect during cerebral ischemic
      injury.

PMID- 28499836
TI  - Inhibitory Control for Emotional and Neutral Scenes in Competition: An Eye
      Tracking Study in Bipolar Disorder.
AB  - This study examined the inhibitory control of attention to social scenes in
      manic, depressive, and euthymic episodes of bipolar disorder (BD). Two scenes
      were simultaneously presented (happy/threatening/neutral [target] versus
      control). Participants were asked either to look at the emotional pictures (i.e.,
      attend-to-emotional block) or to avoid looking at the emotional pictures (i.e.,
      attend-to-neutral block) while their eye movements were recorded. The initial
      orienting (latency and percentage of first fixation) and subsequent attentional
      engagement (gaze duration) were computed. Manic patients showed a higher
      percentage of initial fixations on happy scenes than on the other scenes,
      regardless of the instructions. However, in the attend-to-neutral block, their
      gaze durations were longest for threatening scenes. Inhibitory control was not
      modulated by the scene's emotional salience in the other groups. Thus, manic
      patients had difficulties voluntarily ignoring emotional information - this was
      characterized by a happy-related bias during initial orienting, but a threat
      related bias during attentional engagement.

PMID- 28499837
TI  - Information Processing of the Rorschach's Traumatic Content Index in Trauma
      exposed Adults: An Event Related Potential (ERP) Study.
AB  - PTSD elicits hypervigilance to trauma-related stimuli. Our novel research
      examined event-related potentials from Blood, Anatomy, and Morbid content derived
      from the Rorschach's traumatic content index (TCI). Participants included: 16
      with PTSD, 24 trauma-exposed without PTSD (non-PTSD), and 16 non-traumatized
      Controls. P3 oddball paradigms were used with TCI-derived Distractors and neutral
      Targets/Standards. We predicted larger P3 amplitudes in the context of TCI
      related Distractors among trauma-exposed participants. Significant interaction of
      Group and Distractor type was found for P3 amplitude. PTSD and non-PTSD groups
      exhibited larger P3 amplitudes from Blood and Anatomy Distractors, and attenuated
      amplitudes from Morbid; the reverse pattern was found among Controls. A late
      negative component was observed, denoting a significantly larger area under the
      curve (AUC) among the PTSD group for Anatomy and Blood Distractors. Larger AUC's
      were observed for Distractors among the PTSD group, and Targets among Controls.
      The findings concur with the neurocircuitry model of PTSD and suggest impairment
      in cerebral suppression of attention to stimuli that may have been perceptually
      primed with trauma.

PMID- 28499838
TI  - Brain responses to sound intensity changes dissociate depressed participants and
      healthy controls.
AB  - Depression is associated with bias in emotional information processing, but less
      is known about the processing of neutral sensory stimuli. Of particular interest
      is processing of sound intensity which is suggested to indicate central
      serotonergic function. We tested weather event-related brain potentials (ERPs) to
      occasional changes in sound intensity can dissociate first-episode depressed,
      recurrent depressed and healthy control participants. The first-episode depressed
      showed larger N1 amplitude to deviant sounds compared to recurrent depression
      group and control participants. In addition, both depression groups, but not the
      control group, showed larger N1 amplitude to deviant than standard sounds.
      Whether these manifestations of sensory over-excitability in depression are
      directly related to the serotonergic neurotransmission requires further research.
      The method based on ERPs to sound intensity change is fast and low-cost way to
      objectively measure brain activation and holds promise as a future diagnostic
      tool.

PMID- 28499839
TI  - Does emotion change auditory prediction and deviance detection?
AB  - In the last decades, a growing number of studies provided compelling evidence
      supporting the interplay of cognitive and affective processes. However, it
      remains to be clarified whether and how an emotional context affects the
      prediction and detection of change in unattended sensory events. In an event
      related potential (ERP) study, we probed the modulatory role of pleasant,
      unpleasant and neutral visual contexts on the brain response to automatic
      detection of change in spectral (intensity) vs. temporal (duration) sound
      features. Twenty participants performed a passive auditory oddball task.
      Additionally, we tested the relationship between ERPs and self-reported mood.
      Participants reported more negative mood after the negative block. The P2
      amplitude elicited by standards was increased in a positive context. Mismatch
      Negativity (MMN) amplitude was decreased in the negative relative to the neutral
      and positive contexts, and was associated with self-reported mood. These findings
      suggest that the detection of regularities in the auditory stream was facilitated
      in a positive context, whereas a negative visual context interfered with
      prediction error elicitation, through associated mood changes. Both ERP and
      behavioral effects highlight the intricate links between emotion, perception and
      cognitive processes.

PMID- 28499840
TI  - Antimicrobial peptide KSL-W promotes gingival fibroblast healing properties in
      vitro.
AB  - We investigated the effect of synthetic antimicrobial decapeptide KSL-W
      (KKVVFWVKFK) on normal human gingival fibroblast growth, migration, collagen gel
      contraction, and alpha-smooth muscle actin protein expression. Results show that
      in addition to promoting fibroblast adhesion by increasing F-actin production,
      peptide KSL-W promoted cell growth by increasing the S and G2/M cell cycle
      phases, and enhanced the secretion of metalloproteinase (MMP)-1 and MMP-2 by
      upregulating MMP inhibitors, such as tissue inhibitors of metalloproteinase
      (TIMP)-1 and TIMP-2 in fibroblasts. An in vitro wound healing assay confirmed
      that peptide KSL-W promoted fibroblast migration and contraction of a collagen
      gel matrix. We also demonstrated a high expression of alpha-smooth muscle actin
      by gingival fibroblasts being exposed to KSL-W. This work shows that peptide KSL
      W enhances gingival fibroblast growth, migration, and metalloproteinase
      secretion, and the expression of alpha-smooth muscle actin, thus promoting wound
      healing.

PMID- 28499841
TI  - Effect of administration method, animal weight and age on the intranasal delivery
      of drugs to the brain.
AB  - BACKGROUND: The intranasal route of administration has proven to be an effective
      method for bypassing the blood brain barrier and avoiding first pass hepatic
      metabolism when targeting drugs to the brain. Most small molecules gain rapid
      access to CNS parenchyma when administered intranasally. However, bioavailability
      is affected by various factors ranging from the molecular weight of the drug to
      the mode of intranasal delivery. COMPARISON WITH EXISTING METHODS: We examined
      the effects of animal posture, intranasal application method and animal weight
      and age on the delivery of radiolabeled pralidoxime (3H-2-PAM) to the brain of
      rats. RESULTS: We found that using upright vs. supine posture did not
      significantly affect 3H-2-PAM concentrations in different brain regions. Older
      animals with higher weights required increased doses to achieve the same drug
      concentration throughout the brain when compared to young animals with lower body
      weights. The use of an intranasal aerosol propelled delivery device mainly
      increased bioavailability in the olfactory bulbs, but did not reliably increase
      delivery of the drug to various other brain regions, and in some regions of the
      brain delivered less of the drug than simple pipette administration. CONCLUSION:
      In view of the emerging interest in the use of intranasal delivery of drugs to
      combat cognitive decline in old age, we tested effectiveness in very old rats and
      found the method to be as effective in the older rats.

PMID- 28499842
TI  - Establishing the ferret as a gyrencephalic animal model of traumatic brain
      injury: Optimization of controlled cortical impact procedures.
AB  - BACKGROUND: Although rodent TBI studies provide valuable information regarding
      the effects of injury and recovery, an animal model with neuroanatomical
      characteristics closer to humans may provide a more meaningful basis for clinical
      translation. The ferret has a high white/gray matter ratio, gyrencephalic
      neocortex, and ventral hippocampal location. Furthermore, ferrets are amenable to
      behavioral training, have a body size compatible with pre-clinical MRI, and are
      cost-effective. NEW METHODS: We optimized the surgical procedure for controlled
      cortical impact (CCI) using 9 adult male ferrets. We used subject-specific
      brain/skull morphometric data from anatomical MRIs to overcome across-subject
      variability for lesion placement. We also reflected the temporalis muscle, closed
      the craniotomy, and used antibiotics. We then gathered MRI, behavioral, and
      immunohistochemical data from 6 additional animals using the optimized surgical
      protocol: 1 control, 3 mild, and 1 severely injured animals (surviving one week)
      and 1 moderately injured animal surviving sixteen weeks. RESULTS: The optimized
      surgical protocol resulted in consistent injury placement. Astrocytic reactivity
      increased with injury severity showing progressively greater numbers of
      astrocytes within the white matter. The density and morphological changes of
      microglia amplified with injury severity or time after injury. Motor and
      cognitive impairments scaled with injury severity. COMPARISON WITH EXISTING
      METHOD(S): The optimized surgical methods differ from those used in the rodent,
      and are integral to success using a ferret model. CONCLUSIONS: We optimized
      ferret CCI surgery for consistent injury placement. The ferret is an excellent
      animal model to investigate pathophysiological and behavioral changes associated
      with TBI.

PMID- 28499843
TI  - Magnetic resonance imaging in dissociated strabismus complex demonstrates
      generalized hypertrophy of rectus extraocular muscles.
AB  - BACKGROUND: Dissociated strabismus complex (DSC) is an enigmatic form of
      strabismus that includes dissociated vertical deviation (DVD) and dissociated
      horizontal deviation (DHD). We employed magnetic resonance imaging (MRI) to
      evaluate the extraocular muscles in DSC. METHODS: We studied 5 patients with DSC
      and mean age of 25 years (range, 12-42 years), and 15 age-matched, orthotropic
      control subjects. All patients had DVD; 4 also had DHD. We employed high
      resolution, surface coil MRI with thin, 2 mm slices and central target fixation.
      Volumes of the rectus and superior oblique muscles in the region 12 mm posterior
      to 4 mm anterior to the globe-optic nerve junction were measured in quasi-coronal
      planes in central gaze. RESULTS: Patients with DSC had no structural
      abnormalities of rectus muscles or rectus pulleys or the superior oblique muscle
      but exhibited modest, statistically significant increased volume of all rectus
      muscles ranging from 20% for medial rectus to 9% for lateral rectus (P < 0.05).
      CONCLUSIONS: DSC includes various combinations of sursumduction, excycloduction,
      and abduction not conforming to Hering's law. We have found modest generalized
      enlargement of all rectus muscles. DSC is associated with generalized rectus
      extraocular muscle hypertrophy in the absence of other orbital abnormalities.

PMID- 28499844
TI  - Inconclusive Exercise Stress Echocardiography in Patients With Chest Pain:
      Prevalence and Clinical Determinants.

PMID- 28499845
TI  - Exploring resistance pathways for first-generation NS3/4A protease inhibitors
      boceprevir and telaprevir using Bayesian network learning.
AB  - Resistance-associated variants (RAVs) have been shown to influence treatment
      response to direct-acting antivirals (DAAs) and first generation NS3/4A protease
      inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV)
      genotypic drug resistance remains a challenge, especially in patients who
      previously failed DAA therapy and need to be retreated with a second DAA based
      regimen. Bayesian network (BN) learning on HCV sequence data from patients
      treated with DAAs could provide insight in resistance pathways against PIs for
      HCV subtypes 1a and 1b, in a similar way as applied before for HIV. The publicly
      available 'Rega-BN' tool chain was developed to study associative analyses for
      various pathogens. Our first analysis, comparing sequences from PI-naive and PI
      experienced patients, determined that NS3 substitutions R155K and V36M arise with
      PI-exposure in HCV1a infected patients, and were defined as major and minor
      resistance-associated variants respectively. NS3 variant 174H was newly
      identified as potentially related to PI resistance. In a second analysis, NS3
      sequences from PI-naive patients who cleared the virus during PI therapy and from
      PI-naive patients who failed PI therapy were compared, showing that NS3 baseline
      variant 67S predisposes to treatment-failure and variant 72I to treatment
      success. This approach has the potential to better characterize the role of more
      RAVs, if sufficient therapy annotated sequence data becomes available in curated
      public databases. In addition, polymorphisms present in baseline sequences that
      predispose patients to therapy failure can be identified using this approach.

PMID- 28499846
TI  - Methodological quality is underrated in systematic reviews and meta-analyses in
      health psychology.
AB  - OBJECTIVES: In this paper, we compile and describe the main approaches proposed
      in the literature to include methodological quality (MQ) or risk of bias (RoB)
      into research synthesis. We also meta-review how the RoB of observational primary
      studies is being assessed and to what extent the results are incorporated in the
      conclusions of research synthesis. STUDY DESIGN AND SETTING: Electronic databases
      were searched for systematic reviews or meta-analyses related to health and
      clinical psychology. A random sample of 90 reviews published between January 2010
      and May 2016 was examined. RESULTS: A total of 46 reviews (51%) performed a
      formal assessment of the RoB of primary studies. Only 17 reviews (19%) linked the
      outcomes of quality assessment with the results of the review. CONCLUSION:
      According to the previous literature, our results corroborate the lack of
      guidance to incorporate the RoB assessment in the results of systematic reviews
      and meta-analyses. Our recommendation is to appraise MQ according to domains of
      RoB to rate the degree of credibility of the results of a research synthesis, as
      well as subgroup analysis or meta-regression as analytical methods to incorporate
      the quality assessment.

PMID- 28499847
TI  - GRADE equity guidelines 2: considering health equity in GRADE guideline
      development: equity extension of the guideline development checklist.
AB  - OBJECTIVE: To provide guidance for guideline developers on how to consider health
      equity at key stages of the guideline development process. STUDY DESIGN AND
      SETTING: Literature review followed by group discussions and consensus building.
      RESULTS: The key stages at which guideline developers could consider equity
      include setting priorities, guideline group membership, identifying the target
      audience(s), generating the guideline questions, considering the importance of
      outcomes and interventions, deciding what evidence to include and searching for
      evidence, summarizing the evidence and considering additional information,
      wording of recommendations, and evaluation and use. We provide examples of how
      guidelines have actually considered equity at each of these stages. CONCLUSION:
      Guideline projects should consider the aforementioned suggestions for
      recommendations that are equity sensitive.

PMID- 28499848
TI  - Understanding obesity in the context of an Indigenous population-A qualitative
      study.
AB  - BACKGROUND: Obesity is a progressive global phenomenon that is disparately
      prevalent amongst Indigenous populations. While there is a growing body of
      literature investigating the extrinsic contributors to obesity, there is a lack
      of evidence to elucidate intrinsic drivers in the context of an Indigenous
      population. METHODS: Qualitative research theory, inclusive of Indigenous
      knowledge systems, was applied to the narratives of 15 Indigenous (Maori) people
      aged between 18 and 65 to contextualise their understandings of obesity. RESULTS:
      Thematic analysis of the interview data revealed four intrinsic determinants for
      obesity expression that specifically relate to Indigenous peoples: (1)
      relationships and social connectedness; (2) holistic health including spiritual
      beliefs and cultural practices (Indigenous worldview); (3) historical trauma and
      the impacts of colonisation; and (4) the biomedical model of caloric restriction,
      diet and exercise were culturally insensitive, non-relatable, and were not
      significant drivers for engagement in healthier lifestyles. DISCUSSION AND
      CONCLUSIONS: Similar to non-Indigenous populations, Indigenous understandings of
      obesity are multi-factorial. What was unique about the findings of this study
      were insights into the importance of relational aspects and connectedness to each
      other and the environment, as determinants for obesity expression. This suggests
      that the current individualistic approaches of western medicine to obesity
      management are not culturally aligned with Indigenous peoples ways of being.
      Adopting an ontology of connectedness may represent a more culturally centred
      approach, and help build epistemological resilience to mitigate rising obesity
      incidence in Indigenous populations.

PMID- 28499850
TI  - Skeletal muscle protease activities in the early growth and development of wild
      Atlantic salmon (Salmo salar L.).
AB  - Growth-related dynamics of intracellular protease activities in four year classes
      of the Atlantic salmon (Salmo salar L. 1758) parr and smolts inhabiting salmon
      rivers of northwestern Russia (the White Sea basin) were studied. Cathepsin B,
      cathepsin D, proteasome, and calpain activities in the skeletal muscles of salmon
      were assessed to investigate their relative contribution to the total protein
      degradation as well as to young fish growth process. It was confirmed that
      calpain activity dominates in salmon muscles while proteasome plays a minor role,
      in contrast to terrestrial vertebrates. Calpain and proteasome activities were
      maximal at the early post-larval stage (in parrs 0+) and declined with age (parrs
      1+ through 2+) dropping to the lowest level in salmon smolts. Annual growth
      increments and proteolytic activities of calpains and proteasome in the muscles
      of salmon juveniles changed with age in an orchestrated manner, while lysosomal
      cathepsin activities increased with age. Comparing protease activities and growth
      increments in salmon parr and smolts we suggested that the partial suppression of
      the protein degradation could be a mechanism stimulating efficient growth in
      smoltifying salmon. Growth and smoltification-related dynamics of protease
      activities was quite similar in salmon populations from studied spawning rivers,
      such as Varzuga and Indera; however, some habitat-related differences were
      observed. Growth increments and protease activities varied in salmon parr 0+ (but
      not on later ages) inhabiting either main rivers or small tributaries apparently
      due to habitat difference on the resources for fish growth.

PMID- 28499849
TI  - A geometrically adjustable receive array for imaging marmoset cohorts.
AB  - The common marmoset (Callithrix jacchus) is an increasingly popular animal model
      for translational neuroscience studies, during which anatomical and functional
      MRI can be useful investigative tools. To attain the requisite SNR for high
      resolution acquisitions, the radiofrequency coil must be optimized for the
      marmoset; however, relatively few custom coils have been developed that maximize
      SNR and are compatible with accelerated acquisitions. For the study of large
      populations of animals, the heterogeneity in animal size reduces the
      effectiveness of a "one size fits all" approach to coil sizing and makes coils
      tailored to individual animals cost and time prohibitive. The approach taken in
      this study was to create an 8-channel phased-array receive coil that was
      adjustable to the width of the marmoset head, thereby negating the need for
      tailored coils while still maintaining high SNR. Two marmosets of different size
      were imaged on a 9.4-T small-animal scanner. Consistent SNR was achieved in the
      periphery of the brain between head sizes. When compared to a 15-channel, "one
      size fits all" receive coil, the adjustable coil achieved 57% higher SNR in the
      superior frontal and parietal cortices and 29% higher SNR in the centre of the
      brain. The mean geometry factor of the adjustable coil was less than 1.2 for a 2
      fold reduction factor in the left-right and anterior-posterior directions.
      Geometry factors were compared to the 15-channel coil to guide future designs.
      The adjustable coil was shown to be a practical means for anatomical and echo
      planar imaging of marmoset cohorts.

PMID- 28499852
TI  - Withdrawal of antiepileptic drugs: an individualised approach.

PMID- 28499851
TI  - Effects of nutritional history on stress response in gibel carp (Carassius
      auratus gibelio) and largemouth bass (Micropterus salmoides).
AB  - The stress response of omnivorous gibel carp (Carassius auratus gibelio) and
      carnivorous largemouth bass (Micropterus salmoides) with different nutritional
      history were evaluated. A 2*2 layout, including two fish species (gibel carp or
      largemouth bass) and two nutritional history (fasted or fed to satiation for four
      weeks), was used. After feeding or fasting, the fishes were subjected to an acute
      handling. Fasting resulted in decrease of plasma glucose level and liver glycogen
      content of gibel carp and largemouth bass. After handling stress, plasma levels
      of cortisol, glucose and lactate of gibel carp and largemouth bass increased,
      regardless the fasted fish or fed fish. During the period from 0h to 24h post
      stress, the fasted gibel carp exhibited lower plasma cortisol and glucose levels,
      brain and liver glycogen contents, and liver phosphoenolpyruvate carboxykinase
      (PEPCK) activity compared with the fed counterpart. The plasma glucose level,
      brain glucose level, brain and liver glycogen contents were lower, while the
      liver PEPCK and hexokinase (HK) activities were higher, in the faster largemouth
      bass than the fed counterpart. This study indicates that nutritional history can
      influence stress response of gibel carp and largemouth bass, and the stress
      response is less severe in the fasted fish relative to the fed counterpart. This
      study also reveals that gibel carp and largemouth bass may have different
      strategies in response to fasting and acute handling stress.

PMID- 28499853
TI  - Epilepsy and two evolving societies.

PMID- 28499854
TI  - Curcumin loading potentiates the chemotherapeutic efficacy of selenium
      nanoparticles in HCT116 cells and Ehrlich's ascites carcinoma bearing mice.
AB  - The anticancer properties of selenium (Se) and curcumin nanoparticles in solo
      formulations as well as in combination with other therapeutic agents have been
      proved time and again. Exploiting this facet of the two, we clubbed their
      tumoricidal characteristics and designed curcumin loaded Se nanoparticles (Se
      CurNPs) to achieve an enhanced therapeutic effect. We evaluated their therapeutic
      effects on different cancer cell lines and Ehrlich's ascites carcinoma mouse
      model. In vitro results showed that Se-CurNPs were most effective on colorectal
      carcinoma cells (HCT116) compared to the other cancer cell lines used and
      possessed pleiotropic anticancer effects. The therapeutic effect on HCT116 was
      primarily attributed to an elevated level of autophagy and apoptosis as evident
      from significant up-regulation of autophagy associated (LC3B-II) and pro
      apoptotic (Bax) proteins, down-regulation of anti-apoptotic (Bcl-2) protein and
      Cytochrome c (cyt c) release from mitochondria along with reduced NFkappaB
      signaling and EMT based machineries marked by downregulation of inflammation
      (NFkappaB, phospho-NFkappaB) and epithelial-mesenchymal transition (CD44, N
      cadherin) associated proteins. In vivo studies on Ehrlich's ascites carcinoma
      (EAC) mice model indicated that Se-CurNPs significantly reduced the tumor load
      and enhanced the mean survival time (days) of tumor-bearing EAC mice.

PMID- 28499855
TI  - Electrolyte type and nozzle composition affect the process of vibrating-membrane
      nebulization.
AB  - The size of airborne particles determines their deposition pattern within the
      lungs and therefore, the efficacy of inhalation therapy. The present study
      analyzed factors affecting liquid atomization performed by vibrating-membrane
      technology. First, the process of vibrating-membrane nebulization (eFlow(r)rapid
      and Aeroneb(r) Pro) was challenged with numerous inorganic salts and active
      pharmaceutical ingredients. All investigated samples caused a sigmoidal decrease
      in aerosol droplet size upon an increase in concentration. Calculated dose-effect
      curve characteristics (i.e., half maximal effective sample concentration inducing
      a halfway drop of the droplet size) indicated distinct molar "potency" amongst
      the utilized samples with respect to generation of "adequate" inhalation
      aerosols. Second, the employed solvent (aqueous vs. organic) was shown to amplify
      the electrolyte effect on vibrating-membrane technology (i.e., dose-effect curve
      characteristics and overall aerosol droplet size). Third, besides the sample and
      solvent type, the nozzle composition (diverse metal and polymer coatings) induced
      a strong impact on the current mode of nebulization. Here, coating materials were
      identified, which necessitated higher and lower electrolyte concentrations in
      order to decrease the aerosol droplet size in comparable manner to plain
      nebulizer membranes. Thus, depending on the employed sample type and
      concentration, solvent and nozzle composition, a delivery of "inadequate" or
      "adequate" aerosols for inhalation purpose was observed. Overall, the current
      observations could be used to compile suggestions for the rational design of
      aerosol formulations and nebulizer devices meeting the specific requirements for
      successful inhalation therapy.

PMID- 28499857
TI  - Preface to the special issue "Impact of omics on comparative immunology".

PMID- 28499856
TI  - Measuring Soldier Performance During the Patrol-Exertion Multitask: Preliminary
      Validation of a Postconcussive Functional Return-to-Duty Metric.
AB  - OBJECTIVE: To assess the discriminant validity of the Patrol-Exertion Multitask
      (PEMT), a novel, multidomain, functional return-to-duty clinical assessment for
      active duty military personnel. DESIGN: Measurement development study. SETTING:
      Nonclinical indoor testing facility. PARTICIPANTS: Participants (N=84) were
      healthy control (HC) service members (SMs; n=51) and military personnel (n=33)
      with persistent postconcussive symptoms receiving rehabilitation (mild traumatic
      brain injury [mTBI]). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Known
      groups discriminant validity was evaluated by comparing performance on the PEMT
      in 2 groups of active duty SMs: HCs and personnel with mTBI residual symptoms.
      Participant PEMT performance was based on responses in 4 subtasks during a 12
      minute patrolling scenario: (1) accuracy in identifying virtual improvised
      explosive device (IED) markers and responses to scenario-derived questions from a
      computer-simulated foot patrol; (2) auditory reaction time responses; (3) rating
      of perceived exertion during stepping; and (4) self-reported visual clarity (ie,
      gaze stability) during vertical head-in-space translation while stepping.
      RESULTS: Significant between-group differences for the PEMT were observed in 2 of
      4 performance domains. Postpatrol IED identification task/question responses
      (P=.179) and rating of perceived exertion (P=.133) did not discriminate between
      groups. Participant self-report of visual clarity during stepping revealed
      significant (P<.001) between-group differences. SM reaction time responses to
      scenario-based auditory cues were significantly delayed in the mTBI group in both
      the early (P=.013) and late (P=.002) stages of the PEMT. CONCLUSIONS: Findings
      from this study support the use of a naturalistic, multidomain, complex clinical
      assessment to discriminate between healthy SMs and personnel with mTBI residual
      symptoms. Based on this preliminary study, additional research to further refine
      the PEMT and extend its application to return-to-work outcomes in military and
      civilian environments is warranted.

PMID- 28499859
TI  - Reply to Letter to the Editor by Griffiths et al. commenting on Evans & Allen.

PMID- 28499858
TI  - Enhanced behavioral immune defenses in a C. elegans C-type lectin-like domain
      gene mutant.
AB  - C-type lectin-like domain (CTLD) proteins occupy crucial functions in the immune
      system of vertebrates, but their role in invertebrate immunity is much less
      understood. The nematode Caenorhabditis elegans possesses a highly diverse CTLD
      protein encoding (clec) gene repertoire. A role of C. elegans clec genes in
      pathogen defense is always assumed, yet experimental evidence for clec immune
      function is rare. To systematically test the potential function of clec genes in
      the C. elegans defense against pathogens, we screened 39 clec mutants for
      survival on the Gram-positive pathogen Bacillus thuringiensis (BT18247) and 37
      clec mutants on the Gram-negative pathogen Pseudomonas aeruginosa (PA14). We
      found that clec mutants can exhibit either decreased or, unexpectedly, increased
      resistance to infection. Since we observed high escape behavior for some of the
      clec mutants on BT18247 during the initial screen, we then asked if increased
      pathogen avoidance behavior underlies the increased resistance of some clec
      mutants. We thus tested lawn leaving behavior of the resistant clec-29(ok3181),
      clec-34(ok2120), clec-151(ok2264), and C54G4.4(ok2110) mutant on BT18247. We
      found that C54G4.4(ok2110) mutant animals exhibit a particularly strong lawn
      leaving behavior, in addition to prolonged feeding cessation when exposed to
      BT18247. Together, our results indicate that clec genes mediate both resistance
      and susceptibility to infection. Further, behavioral analyses of the
      C54G4.4(ok2110) mutant implicate C54G4.4 in the regulation of pathogen avoidance
      behavior towards BT18247. We conclude that C. elegans clec genes may act both as
      positive and negative regulators of physiological as well as behavioral immune
      defense responses.

PMID- 28499860
TI  - Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of
      Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung
      Adenocarcinoma.

PMID- 28499861
TI  - The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program
      Efficiency.
AB  - INTRODUCTION: Lung cancer risk prediction models have the potential to make
      programs more affordable; however, the economic evidence is limited. METHODS:
      Participants in the National Lung Cancer Screening Trial (NLST) were
      retrospectively identified with the risk prediction tool developed from the
      Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk
      subgroup was assessed for lung cancer incidence and demographic characteristics
      compared with those in the low-risk subgroup and the Pan-Canadian Early Detection
      of Lung Cancer Study (PanCan), which is an observational study that was high-risk
      selected in Canada. A comparison of high-risk screening versus standard care was
      made with a decision-analytic model using data from the NLST with Canadian cost
      data from screening and treatment in the PanCan study. Probabilistic and
      deterministic sensitivity analyses were undertaken to assess uncertainty and
      identify drivers of program efficiency. RESULTS: Use of the risk prediction tool
      developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
      with a threshold set at 2% over 6 years would have reduced the number of
      individuals who needed to be screened in the NLST by 81%. High-risk screening
      participants in the NLST had more adverse demographic characteristics than their
      counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015
      Canadian dollars) per quality-adjusted life-year gained and would be considered
      cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars
      per quality-adjusted life-year gained with a probability of 0.62. Cost
      effectiveness was driven primarily by non-lung cancer outcomes. Higher
      noncurative drug costs or current costs for immunotherapy and targeted therapies
      in the United States would render lung cancer screening a cost-saving
      intervention. CONCLUSIONS: Non-lung cancer outcomes drive screening efficiency in
      diverse, tobacco-exposed populations. Use of risk selection can reduce the budget
      impact, and screening may even offer cost savings if noncurative treatment costs
      continue to rise.

PMID- 28499862
TI  - Successful Revascularization of Aortic Arch in a 39-Year-Old Blunt Trauma Patient
      with Acute Diffuse Axonal Injury without the Use of Systemic Anticoagulation.
AB  - Blunt traumatic aortic injury is the second leading cause of death in trauma
      patients aged 4-34 years. Of the patients who are able to receive treatment,
      mortality rates as high as 40% have been reported. Endovascular repair options
      have allowed for more expeditious repairs with reduced iatrogenic trauma;
      however, when the injury involves the ascending aorta or arch, current endografts
      lack fenestrations needed for cerebral blood flow. Traditionally, on pump,
      cardiopulmonary bypass with systemic anticoagulation has been used to repair
      these injuries. In this paper, we describe a unique case of repairing a large
      traumatic aortic arch pseudoaneurysm in the setting of which systemic
      anticoagulation is contraindicated. The patient is a 39-year-old otherwise
      healthy Hispanic male who presented to Ryder Trauma Center in Miami, Florida,
      following a motor vehicle collision and found to have multiple intracranial
      hemorrhages and a large aortic pseudoaneurysm of the distal ascending aorta. In
      lieu of standard cardiopulmonary bypass, a hybrid approach was utilized. Cranial
      blood flow was maintained using a temporary extra-anatomical left femoral to
      bilateral carotid bypass during endovascular coverage of the aortic arch. Aortic
      arch revascularization was then achieved by means of in situ laser fenestration
      of the innominate artery followed by a right-to-left carotid-carotid-subclavian
      bypass. This case demonstrates the viability of a hybrid vascular repair of a
      complex aortic disruption without the use of systemic anticoagulation in the
      setting of contraindicated or unknown risk of systemic anticoagulation. Further
      research is warranted on whether emergent traumatic cases with contraindications
      to anticoagulation can be performed in a similar fashion to safely reduce the
      morbidity and mortality associated with aortic disruptions.

PMID- 28499863
TI  - Innovative Procedure for Inferior Mesenteric Artery Embolization Using the
      Amplatzer Vascular Plug 4 during Endovascular Aneurysm Repair.
AB  - PURPOSE: The aim of this study is to present an easy and quick technique for
      embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm
      repair (EVAR). TECHNIQUE: We performed IMA embolization using a conventional EVAR
      device alone with the femoral artery approach during EVAR, which has not been
      reported previously. First, a 16F or 18F DrySeal Sheath is inserted from the
      femoral artery into the site around the IMA. Second, cannulation is performed in
      the IMA with an angiography catheter having a 0.038-inch inner lumen that is used
      for gate cannulation during EVAR. Third, IMA embolization is performed using the
      Amplatzer Vascular Plug 4 (AVP4). The use of the DrySeal Sheath facilitates
      cannulation of the IMA, and its combination with a stent-graft balloon allows the
      AVP4 to be placed at the root of the IMA without deviation of the catheter. The
      success rate of the procedure was 90.9% (30/33 cases). The median procedure time
      was 11.6 min. No complications due to IMA embolization were noted. CONCLUSION:
      This procedure enables safe and quick placement of the AVP4 in the IMA using the
      catheter insertion approach from the femoral artery, which has been
      conventionally regarded as difficult.

PMID- 28499864
TI  - Role of hepatitis B core protein in HBV transcription and recruitment of histone
      acetyltransferases to cccDNA minichromosome.
AB  - The hepatitis B core protein (HBc) has been suggested to interact with covalently
      closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription.
      However, direct evidence is lacking. We aimed to identify the specific HBc
      region(s) responsible for transcription regulation and its interaction with
      cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of
      the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations
      on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were
      measured. The association of cccDNA with mutant HBc and histone
      acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP).
      Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV
      resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc
      arginine clusters III and IV mutants also had a significantly lower levels of
      intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type;
      P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants
      had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants,
      the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD
      arginine residues at clusters III and IV play an important role in the regulation
      of HBV transcription as well as subsequent replication steps, likely through the
      reduced interaction of HBc with cccDNA and reduced acetylation of cccDNA-bound
      histones. These findings may provide clues to the identification of novel
      therapeutic targets against HBV.

PMID- 28499865
TI  - Implication of altered autonomic control for orthostatic tolerance in SCI.
AB  - Neural output from the sympathetic and parasympathetic branches of the autonomic
      nervous system (ANS) are integrated to appropriately control cardiovascular
      responses during routine activities of daily living including orthostatic
      positioning. Sympathetic control of the upper extremity vasculature and the heart
      arises from the thoracic cord between T1 and T5, whereas splanchnic bed and lower
      extremity vasculature receive sympathetic neural input from the lower cord
      between segments T5 and L2. Although the vasculature is not directly innervated
      by the parasympathetic nervous system, the SA node is innervated by post
      ganglionic vagal nerve fibers via cranial nerve X. Segmental differences in
      sympathetic cardiovascular innervation highlight the effect of lesion level on
      orthostatic cardiovascular control following spinal cord injury (SCI). Due to
      impaired sympathetic cardiovascular control, many individuals with SCI,
      particularly those with lesions above T6, are prone to orthostatic hypotension
      (OH) and orthostatic intolerance (OI). Symptomatic OH, which may result in OI, is
      a consequence of episodic reductions in cerebral perfusion pressure and the
      symptoms may include: dizziness, lightheadedness, nausea, blurred vision, ringing
      in the ears, headache and syncope. However, many, if not most, individuals with
      SCI who experience persistent and episodic hypotension and OH do not report
      symptoms of cerebral hypoperfusion and therefore do not raise clinical concern.
      This review will discuss the mechanism underlying OH and OI following SCI, and
      will review our knowledge to date regarding the prevalence, consequences and
      possible treatment options for these conditions in the SCI population.

PMID- 28499866
TI  - Identification and characterization of novel lncRNAs in Arabidopsis thaliana.
AB  - Long noncoding RNAs (lncRNAs) are important regulators of various biological
      processes, but few studies have identified lncRNAs in plants; genome-wide
      discovery of novel lncRNAs is thus required. We used deep strand-specific
      sequencing (ssRNA-seq) to obtain approximately 62 million reads from all
      developmental stages of Arabidopsis thaliana and identified 156 novel lncRNAs
      that we classified according to their localization. These novel identified
      lncRNAs showed low expression levels and sequence conservation. Bioinformatic
      analysis predicted potential target genes or cis-regulated genes of 91 antisense
      and 32 intergenic lncRNAs. Functional annotation of these potential targets and
      sequence motif analysis indicated that the lncRNAs participate in various
      biological processes underlying Arabidopsis growth and development. Seventeen of
      the lncRNAs were predicted targets of 22 miRNAs, and a network of interactions
      between ncRNAs and mRNAs was constructed. In addition, nine lncRNAs functioned as
      miRNA precursors. Finally, qRT-PCR revealed that novel lncRNAs have stage- and
      tissue-specific expression patterns in A. thaliana. Our study provides insight
      into the potential functions and regulatory interactions of novel Arabidopsis
      lncRNAs, and enhances our understanding of plant lncRNAs, which will facilitate
      functional research.

PMID- 28499867
TI  - Glycine-nitronyl nitroxide conjugate protects human umbilical vein endothelial
      cells against hypoxia/reoxygenation injury via multiple mechanisms and
      ameliorates hind limb ischemia/reperfusion injury in rats.
AB  - Oxidative stress and inflammation play important roles in the pathogenesis of
      ischemia/reperfusion (I/R)-injury. The administration of antioxidants and anti
      inflammatory agents has been applied to prevent I/R-injury for several decades.
      Of the numerous compounds administrated therapeutically in anti-oxidative stress,
      nitronyl nitroxide has gained increasing attention due to its continuous ability
      to scavenge active oxygen radicals. However, its effect is not ideal in clinical
      therapy. In previous study, we linked the anti-inflammatory amino acid glycine to
      nitronyl nitroxide and developed a novel glycine-nitronyl nitroxide (GNN)
      conjugate, which showed a synergetic protection against renal
      ischemia/reperfusion injury. However, the underlying mechanism remains unclear.
      In this study, a hypoxia/reoxygenation (H/R) injury model was established in
      human umbilical vein endothelial cells (HUVECs) and we found that the GNN
      conjugate significantly elevated the cell viability via reducing the apoptosis
      rate in H/R-treated HUVECs. Meanwhile, GNN conjugate attenuated H/R induced
      mitochondrial fragmentation, mitochondrial membrane potential reduction,
      Cytochrome c release and autophagy. To determine the extensive applicability of
      GNN conjugate in different I/R models and its effect in remote organs, an in vivo
      hind limb I/R model was established. As expected, GNN conjugate ameliorated
      damages of muscle and remote organs. These results demonstrate that GNN conjugate
      may be an effective agent against ischemia/reperfusion injury in clinical
      therapy.

PMID- 28499868
TI  - Exposure to particulate matter induces cardiomyocytes apoptosis after myocardial
      infarction through NFkappaB activation.
AB  - Clinical evidence has indicated an increased myocardial infarction (MI) morbidity
      and mortality after exposure to air pollution (particulate matter<2.5 MUm,
      PM2.5). However, the mechanisms by which PM2.5 aggravates MI remain unknown.
      Present study was to explore the adverse effect of PM2.5 on myocardium after MI
      and the potential mechanisms. Male mice with MI surgery were treated with PM2.5
      by intranasal instillation. Neonatal mice ventricular myocytes (NMVMs) subjected
      to hypoxia were also incubated with PM2.5 to determine the role of PM2.5 in
      vitro. Exposure to PM2.5 significantly impaired the cardiac function and
      increased the infarct size in MI mice. TUNEL assay, flow cytometry and western
      blotting of Caspase 3, Bax and BCl-2 indicated that PM2.5 exposure could cause
      cellular apoptosis in vivo and in vitro. Besides, PM2.5 activated NFkappaB
      pathway and increased gene expression of IL-1beta and IL-6 in NMVMs with hypoxia,
      which could be effectively reversed by SN-50-induced blockade of NFkappaB
      translocation to the nucleus. In summary, air pollution induces myocardium
      apoptosis and then impairs cardiac function and aggravates MI via NFkappaB
      activation.

PMID- 28499869
TI  - RNF8 negatively regulates NF-kappaB signaling by targeting IkappaB kinase:
      implications for the regulation of inflammation signaling.
AB  - Persistent or excess activation of NF-kappaB leads to cancer, autoimmune and
      inflammatory diseases. Therefore, activated NF-kappaB needs to be terminated
      after induction, which highlights the physiological significance of NF-kappaB
      negative regulators. However, the molecular mechanisms that negatively regulate
      NF-kappaB are not well understood. Here, we report that Ring Finger Protein 8
      (RNF8), an E3 ubiquitin ligase, inhibits TNFalpha-mediated NF-kappaB activation
      by targeting IkappaB kinase (IKK). Upon TNFalpha stimulation, RNF8 binds to the
      catalytic subunits of IKK complex, resulting in inhibition of IKKalpha/beta
      phosphorylation and subsequent NF-kappaB activation. RNF8 targets the IKK complex
      in a manner independent of its RING domain. We further provide evidence that the
      silencing of RNF8 results in enhanced TNFalpha-induced IKK activation, and an
      increase expression of NF-kappaB-induced inflammatory cytokine IL-8. Our study
      identifies a previously unrecognized role for RNF8 in the negative regulation of
      NF-kappaB activation by targeting and deactivating the IKK complex.

PMID- 28499870
TI  - Fibronectin on extracellular vesicles from microvascular endothelial cells is
      involved in the vesicle uptake into oligodendrocyte precursor cells.
AB  - We previously reported transplantation of brain microvascular endothelial cells
      (MVECs) into cerebral white matter infarction model improved the animal's
      behavioral outcome by increasing the number of oligodendrocyte precursor cells
      (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted
      survival and proliferation of OPCs in vitro. In this study, we investigated the
      mechanism how EVs derived from MVECs contribute to OPC survival and
      proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay
      revealed fibronectin was abundant on the surface of EVs from MVECs. As
      fibronectin has been reported to promote OPC survival and proliferation via
      integrin signaling pathway, we blocked the binding between fibronectin and
      integrins using RGD sequence mimics. Blocking the binding, however, did not
      attenuate the survival and proliferation promoting effect of EVs on OPCs. Flow
      cytometric and imaging analyses revealed fibronectin on EVs mediates their
      internalization into OPCs by its binding to heparan sulfate proteoglycan on OPCs.
      OPC survival and proliferation promoted by EVs were attenuated by blocking the
      internalization of EVs into OPCs. These lines of evidence suggest that
      fibronectin on EVs mediates their internalization into OPCs, and the cargo of EVs
      promotes survival and proliferation of OPCs, independent of integrin signaling
      pathway.

PMID- 28499871
TI  - Synthesis of a new deoxyglucose derivative modified near-infrared fluorescent
      probe for tumor diagnosis.
AB  - Malignant neoplasms exhibit an elevated rate of glycolysis and a high demand for
      glucose over normal cells. This characteristic can be exploited for in vivo
      imaging and tumor targeting examined. In this manuscript, we describe the
      synthesis of near-infrared (NIR) fluorochrome IR-822-labeled 2-amino-2-deoxy-d
      glucose (DG) for optical imaging of tumors in mice. NIR fluorescent dye IR-820
      was subsequently conjugated with 3-Mercaptopropionic acid and 2-amino-2-deoxy-d
      glucose to form IR-822-DG. The cell experiments and acute toxicity studies
      demonstrated the low toxicity of IR-822-DG to normal cells/tissues. The dynamic
      behavior and targeting ability of IR-822-DG in normal mice was investigated with
      a NIR fluorescence imaging system. The in vitro and in vivo tumor targeting
      capabilities of IR-822-DG were evaluated in tumor cells and tumor bearing mice,
      respectively. Results demonstrated that IR-822-DG actively and efficiently
      accumulated at the site of the tumor. The probe also exhibited good
      photostability and excellent cell membrane permeability. The study indicates the
      broad applicability of IR-822-DG for tumors diagnosis, especially in the glucose
      related pathologies.

PMID- 28499872
TI  - Interaction of Flavivirus with their mosquito vectors and their impact on the
      human health in the Americas.
AB  - Some of the major arboviruses with public health importance, such as dengue,
      yellow fever, Zika and West Nile virus are mosquito-borne or mosquito-transmitted
      Flavivirus. Their principal vectors are from the family Culicidae, Aedes aegypti
      and Aedes albopictus being responsible of the urban cycles of dengue, Zika and
      yellow fever virus. These vectors are highly competent for transmission of many
      arboviruses. The genetic variability of the vectors, the environment and the
      viral diversity modulate the vector competence, in this context, it is important
      to determine which vector species is responsible of an outbreak in areas where
      many vectors coexist. As some vectors can transmit several flaviviruses and some
      flaviviruses can be transmitted by different species of vectors, through this
      review we expose importance of yellow fever, dengue and Zika virus in the world
      and the Americas, as well as the updated knowledge about these flaviviruses in
      their interaction with their mosquito vectors, guiding us on what is probably the
      beginning of a new stage in which the simultaneity of outbreaks will occur more
      frequently.

PMID- 28499873
TI  - Inhibition of bioluminescence in the living gills of the luminous fungus Mycena
      chlorophos by trans-4-aminocinnamic acid.
AB  - The living gills of the fungus Mycena chlorophos spontaneously emit green light.
      It was previously reported that trans-4-hydroxycinnamic acid and trans-3,4
      dihydroxycinnnamic acid are essential for the bright light production in the
      living gills. However, the chemical mechanisms underlying their bioluminescence
      are unknown. In the present study, trans-4-aminocinnamic acid was found to
      inhibit light production in the living gills. The concentrations of trans-4
      aminocinnamic acid that inhibited the bioluminescence intensity by 50% of initial
      values for immature and mature gills were 0.07 MUM and 4 MUM, respectively.
      Approximately 20% of the bioluminescence intensity of the immature and mature
      gills was not inhibited by a further increase in the concentration of trans-4
      aminocinnamic acid. Moreover, the bioluminescence that was activated by trans-4
      hydroxycinnamic acid or trans-3,4-dihydroxycinnamic acid (0.01 mM) was completely
      inhibited by trans-4-aminocinnamic acid. Therefore, trans-4-hydroxycinnamic acid
      and trans-3,4-dihydroxycinnamic acid functioned for the bioluminescence that was
      inhibited by trans-4-aminocinnamic acid. trans-4-Aminocinnamic acid strongly
      bound to the bioluminescence system(s) and withstood rinsing of the gills with 10
      mM phosphate buffer (pH = 7), and high concentrations of trans-4-hydroxycinnamic
      acid (1 mM) and trans-3,4-dihydroxycinnamic acid (0.1 mM) functioned to displace
      trans-4-aminocinnamic acid from the bioluminescence system(s) and reactivate
      bioluminescence. Benzenamine, trans-cinnamic acid, trans-2-aminocinnamic acid,
      and trans-3-aminocinnamic acid did not inhibit bioluminescence. Therefore, the
      structure-specific inhibition by trans-4-aminocinnamic acid suggested that the 4
      hydroxy group in trans-4-hydroxycinnamic acid and trans-3,4-dihydroxycinnamic
      acid molecules plays a functional role in the bioluminescence reaction.

PMID- 28499874
TI  - Pyrrole-indolinone SU11652 targets the nucleoside diphosphate kinase from
      Leishmania parasites.
AB  - Nucleoside diphosphate kinases (NDKs) are key enzymes in the purine-salvage
      pathway of trypanosomatids and have been associated with the maintenance of host
      cell integrity for the benefit of the parasite, being potential targets for
      rational drug discovery and design. The NDK from Leishmania major (LmNDK) and
      mutants were expressed and purified to homogeneity. Thermal shift assays were
      employed to identify potential inhibitors for LmNDK. Calorimetric experiments,
      site-directed mutagenesis and molecular docking analysis were performed to
      validate the interaction and to evaluate the structural basis of ligand
      recognition. Furthermore, the anti-leishmanial activity of the newly identified
      and validated compound was tested in vitro against different Leishmania species.
      The molecule SU11652, a Sunitinib analog, was identified as a potential inhibitor
      for LmNDK and structural studies indicated that this molecule binds to the active
      site of LmNDK in a similar conformation to nucleotides, mimicking natural
      substrates. Isothermal titration calorimetry experiments combined with site
      directed mutagenesis revealed that the residues H50 and H117, considered
      essential for catalysis, play an important role in ligand binding. In vitro cell
      studies showed that SU11652 had similar efficacy to Amphotericin b against some
      Leishmania species. Together, our results indicate the pyrrole-indolinone SU11652
      as a promising scaffold for the rational design of new drugs targeting the enzyme
      NDK from Leishmania parasites.

PMID- 28499875
TI  - Natural zwitterionic l-Carnitine as efficient cryoprotectant for solvent-free
      cell cryopreservation.
AB  - Organic solvents, such as dimethyl sulfoxide (DMSO) and glycerol, have been
      commonly used as cryoprotectants (CPAs) in cell cryopreservation. However, their
      cytotoxicity and need of complex freezing protocols have impeded their
      applications especially in clinical cell therapy and regenerative medicine.
      Trehalose has been explored as a natural CPA to cryopreserve cells, but its poor
      cell permeability frequently results in low cryopreservation efficacy. In this
      work, we presented that a natural zwitterionic molecule-l-carnitine-could serve
      as a promising CPA for solvent-free cryopreservation. We demonstrated that l
      carnitine possessed strong ability to depress water freezing point, and with
      ultrarapid freezing protocol, we studied the post-thaw survival efficiency of
      four cell lines (GLC-82 cells, MCF-7 cells, NIH-3T3 cells and Sheep Red Blood
      Cells) using l-carnitine without addition of any organic solvents. At the optimum
      l-carnitine concentration, all four cell lines could achieve above 80% survival
      efficiency, compared with the significantly lower efficiency using organic CPAs
      and trehalose. After cryopreservation, the recovered cell behaviors including
      cell attachment and proliferation were found to be similar to the normal cells,
      indicating that the cell functionalities were not affected. Moreover, l-carnitine
      showed no observable cytotoxicity, which was superior to the organic CPAs. This
      work offered an attractive alternative to traditional CPAs and held great promise
      to revolutionize current cryopreservation technologies, to benefit the patients
      in various cell-based clinical applications.

PMID- 28499876
TI  - MR imaging for accurate prediction of outcome after perinatal arterial ischemic
      stroke: Sooner not necessarily better.
AB  - BACKGROUND: Involvement of the corticospinal tracts after perinatal arterial
      ischemic stroke (PAIS) is strongly correlated with adverse motor outcome.
      METHODS: Two full-term infants with PAIS, with two early MRI scans available, are
      reported. RESULTS: Diffusion weighted imaging (DWI)-MRI, performed within 24 h
      following onset of seizures and repeated 48 h later, clearly showed restricted
      diffusion within the middle cerebral artery territory on both MRIs, but clear
      patterns of signal intensity changes in the descending corticospinal tracts on
      the second MRI only. CONCLUSION: Since involvement of the corticospinal tracts is
      essential for prediction of motor outcome, we may need to reconsider optimal
      timing of MR imaging for prediction of neurodevelopmental outcome after PAIS.

PMID- 28499877
TI  - Novel Superparamagnetic Microdevices Based on Magnetized PLGA/PLA Microparticles
      Obtained by Supercritical Fluid Emulsion and Coating by Carboxybetaine
      Functionalized Chitosan Allowing the Tuneable Release of Therapeutics.
AB  - When superparamagnetic nanoparticles (MAG) are loaded within microcarriers of
      thermosensitive and injectable biopolymers, "smart" microdevices are obtained:
      they respond to an external magnetic field through the release of any co
      encapsulated molecules with a remote on-off control. Creating reliable and
      effective fabrication technologies for the production of these smart
      nano/microdevices remains a challenge. In this work, supercritical emulsion
      extraction technology is proposed for the fabrication of microcapsules with a
      core of poly-lactic-co-glycolic acid (PLGA) or polylactic acid (PLA) covered by
      carboxybetaine-functionalized chitosan (f-chi) and loaded with MAG (mean size of
      6.5 +/- 3.0 nm) and water-soluble fluorescein (Fluo). Fluo is co-encapsulated as
      a fluorescent marker for the release study. Microcarriers showed a mean size of
      800 +/- 60 nm with an encapsulation efficiency of up to 90%. The inversion of
      surface charge, after the f-chi coating, suggested the presence of a uniform
      functionalized surface available for further chemical linkage. The external
      chitosan layer had a thickness of 200 +/- 50 nm. An excellent MAG dispersion was
      confirmed within the biopolymer matrix that was shown to be responsive to
      external magnetic field; indeed, Fluo was released over 3 or 5 days from PLGA or
      f-chi-PLGA microdevices into phosphate-buffered saline medium at 37 degrees C,
      whereas remote on-off controlled release was achieved when an alternating
      magnetic field was applied.

PMID- 28499878
TI  - Possible Role of Organic Cation Transporters in the Distribution of
      [11C]Sulpiride, a Dopamine D2 Receptor Antagonist.
AB  - We synthesized [11C]sulpiride as a positron emission tomography probe for
      investigating the drug distribution in the human body. [11C]Sulpiride was
      injected to healthy male subjects in either tracer dose of [11C]sulpiride
      (approximately 222 MBq) or with therapeutic dose of sulpiride (500 mg, peroral) 3
      h before the injection in a crossover fashion. Whole-body positron emission
      tomography imaging demonstrated that [11C]sulpiride accumulated exceedingly in
      the bladder, followed by liver, gall bladder, and kidney, respectively, at 30 min
      after the injection, whereas scarcely in the brain. Oral dose of sulpiride
      decreased the hepatic accumulation of the radioactivity by 60%. From in vitro
      experiments, we found that sulpiride is a substrate of hOCT1 (Km 2.6 MUM), hOCT2
      (Km 68 MUM), hMATE1 (Km 40 MUM), and hMATE2-K (Km 60 MUM). Moreover, the uptake
      of sulpiride by human hepatocytes was diminished by tetraethylammonium, and
      saturable with Km of 18 MUM. Oct1/2 double knockout mice and wild-type mice
      received Mate1 inhibitors (pyrimethamine/cimetidine) manifested reduced renal
      clearance of sulpiride, accompanied with its accumulation in the plasma. In
      conclusion, we found that sulpiride is a substrate of OCT1, OCT2, MATE1, and
      MATE2-K, and this suggests that [11C]sulpiride would be a useful radioligand to
      investigate the organic cation transporters in humans.

PMID- 28499879
TI  - Developing a Flexible Pediatric Dosage Form for Antiretroviral Therapy: A Fast
      Dissolving Tablet.
AB  - Current presentations of the anti-HIV drugs lopinavir and ritonavir make
      appropriate dosing for children difficult. We conducted a feasibility study to
      develop a formulation for these drugs with child-safe excipients in a flexible
      dosage form for children across the pediatric age spectrum. The freeze-drying in
      blister approach was used to produce fast-dissolving tablets (FDTs), as these can
      be dispersed in fluids for easy administration, even to infants, and appropriate
      portions of the dispersion can be given for different ages/weights. We combined
      various ratios of polymers, surfactants, and bulking agents to incorporate the 2
      highly hydrophobic drugs while maintaining drug stability, rapid disintegration,
      and good handling properties. The final FDT was robust and disintegrated in 0.5
      mL of fluid in 10 s with up to 4 tablets dissolving in 2 mL to achieve varying
      doses accommodated in a common teaspoon. Drug recovery after dissolution in small
      volumes of liquid or fluid foods was 90%-105%. The final candidate FDT was stable
      at 40 degrees C, 75% relative humidity for up to 3 months. FDTs are a promising
      flexible dosage form for antiretroviral treatment for pediatric patients,
      especially in low-resource settings.

PMID- 28499880
TI  - Photoprotection strategies of the alga Nannochloropsis gaditana.
AB  - Nannochloropsis spp. are algae with high potential for biotechnological
      applications due to their capacity to accumulate lipids. However, little is known
      about their photosynthetic apparatus and acclimation/photoprotective strategies.
      In this work, we studied the mechanisms of non-photochemical quenching (NPQ), the
      fast response to high light stress, in Nannochloropsis gaditana by "locking" the
      cells in six different states during quenching activation and relaxation.
      Combining biochemical analysis with time-resolved fluorescence spectroscopy, we
      correlated each NPQ state with the presence of two well-known NPQ components: de
      epoxidized xanthophylls and stress-related antenna proteins (LHCXs). We
      demonstrated that after exposure to strong light, the rapid quenching that takes
      place in the antennas of both photosystems was associated with the presence of
      LHCXs. At later stages, quenching occurs mainly in the antennas of PSII and
      correlates with the amount of de-epoxidised xanthophylls. We also observed
      changes in the distribution of excitation energy between photosystems, which
      suggests redistribution of excitation between photosystems as part of the photo
      protective strategy. A multistep model for NPQ induction and relaxation in N.
      gaditana is discussed.

PMID- 28499881
TI  - Spectral dependence of irreversible light-induced fluorescence quenching:
      Chlorophyll forms with maximal emission at 700-702 and 705-710nm as spectroscopic
      markers of conformational changes in the core complex.
AB  - The spectral dependence of the irreversible non-photochemical fluorescence
      quenching associated with photoinhibition in vitro has been comparatively
      investigated in thylakoid membranes, PSII enriched particles and PSII core
      complexes isolated from spinach. The analysis of the fluorescence emission
      spectra of dark-adapted and quenched samples as a function of the detection
      temperature in the 280-80K interval, indicates that Chlorophyll spectral forms
      having maximal emission in the 700-702nm and 705-710nm ranges gain relative
      intensity in concomitance with the establishment of irreversible light-induced
      quenching, acting thereby as spectroscopic markers. The relative enhancement of
      the 700-702nm and 705-710nm forms emission could be due either to an increase of
      their stoichiometric abundance or to their intrinsically low fluorescence quantum
      yields. These two factors, that can also coexist, need to be promoted by light
      induced alterations in chromophore-protein as well as chromophore-chromophore
      interactions. The bands centred at about 701 and 706nm are also observed in the
      PSII core complex, suggesting their, at least partial, localisation in proximity
      to the reaction centre, and the occurrence of light-induced conformational
      changes in the core subunits.

PMID- 28499883
TI  - The role of 5-hydroxymethylcytosine in development, aging and age-related
      diseases.
AB  - DNA methylation at the fifth position of cytosines (5mC) represents a major
      epigenetic modification in mammals. The recent discovery of 5
      hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our
      view of the epigenome, as multiple studies indicate that 5hmC is not simply an
      intermediate of DNA demethylation, but a genuine epigenetic mark that may play an
      important functional role in gene regulation. Currently, the availability of
      platforms that discriminates between the presence of 5mC and 5hmC at single-base
      resolution is starting to shed light on the functions of 5hmC. In this review, we
      provide an overview of the genomic distribution of 5hmC, and examine recent
      findings on the role of this mark and the potential consequences of its
      misregulation during three fundamental biological processes: cell
      differentiation, cancer and aging.

PMID- 28499882
TI  - [Effect of several methods of scarification and osmotic stress on seed
      germination of Robinia pseudoacacia L.]
AB  - The planting of several species adapted to forests areas in the Saharan Atlas
      would allow one to better fight against the desertification of the vegetation
      cover of these fragile areas. Thanks to its rapid growth on degraded soils,
      Robinia pseudoacacia L. has an advantage in the repopulation of these areas
      undergoing desertification. Operation of this large-scale tree requires good
      control of germination conditions and growth of plants. The scarification of the
      seeds of Robinia pseudoacacia L. is necessary to allow the absorption of water by
      the seeds. Our results show that mechanical scarification with sulphuric acid
      (75minutes), boiling water (90minutes) and scarification by microwaves (700W)
      (105seconds) give the best germination rates. The presence of PEG6000 in the
      imbibition's solutions reduces considerably the germination rate of the seeds of
      R. pseudoacacia L. A 70 % decrease in the optimal rate of germination is observed
      when the osmotic pressure of the imbibition solution is at -4.65 bar.

PMID- 28499884
TI  - Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial
      mesenchymal transition and promotes stemness in mammary epithelial cells.
AB  - Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that
      regulates Axin stability and plays a critical role in Wnt/beta-catenin signaling.
      We sought to investigate the role of USP34 on epithelial-mesenchymal (EMT)
      induction and its effects on mammary epithelial stem cells. USP34 expression
      levels were relatively lower in MDA-MB-231 and 4T1 mesenchymal-like cells when
      compared to epithelial-like cells. Inhibition of USP34 in NMuMG cells induced
      EMT, as evidenced by the upregulation of EMT markers including N-cadherin,
      phospho-Smad3, Snail and active-beta-catenin, as well as the downregulation of
      Axin 1 and E-cadherin. USP34 knockdown (KD) in these cells also resulted in the
      acquisition of invasive behavior, and promoted stemness as indicated by enhanced
      mammosphere-forming ability, concomitant with the upregulation of Nanog, Oct4 and
      Sox2 mRNA expression. Endogenous USP34 expression was observed to be at low
      levels in virgin mouse mammary glands in vivo. When USP34-KD cells were
      transplanted into the cleared mammary fat pads (CFP) of mice, these cells
      reconstituted the mammary gland with ductal tree development within 3months. Our
      findings suggest a previously unknown role for USP34 in mammary gland
      development.

PMID- 28499886
TI  - Ambulatory surgery for sleeve gastrectomy: terminology and concept.

PMID- 28499885
TI  - The role of GILZ in modulation of adaptive immunity in a murine model of
      myocardial infarction.
AB  - Myocardial infarction (MI) is associated with intense immune and inflammatory
      responses which contribute to tissue injury. Increasing evidence indicates that
      the glucocorticoid-induced leucine zipper (GILZ) protein suppresses immune and
      inflammatory responses. However, the status of and the role of GILZ in MI are not
      known. We tested the hypotheses that a) MI reduces cardiac GILZ associated with
      intense inflammation and cell death and b) intramyocardial GILZ delivery confers
      cardioprotection in association with increased Tregs and suppression of
      inflammation. Male Balb/C mice were subjected to MI or sham operation; the
      infarcted animals were subdivided to receive intramyocardial injections of PBS,
      GILZ overexpressing cells (GILZ) or their controls expressing the green
      fluorescent protein (GFP). Three hours after the procedures, hearts were procured
      for subsequent analyses. MI markedly reduced cardiac GILZ expression accompanied
      with a) increase in Th-17 cells (i.e., CD3+CD4+IL-17+ BNP-) but decrease in Tregs
      (i.e., CD3+CD4+FoxP3+BNP-), and b) disruption of mitochondrial membrane potential
      (psim) associated with significant increases in apoptotic and necrotic cell
      death. While both GILZ and GFP returned the aforementioned parameters towards
      those of sham controls, these effects were most marked for mice receiving GILZ.
      Thus, GILZ markedly reduced Th-17 cells but increased Tregs and the anti
      inflammatory cytokine, IL-10 positive cells accompanied with preservation of psim
      and prevention of cell death. To our knowledge, this is the first report
      indicating an important role for GILZ in MI, in part via modulation of adaptive
      immune response, which raises the prospect of exogenous GILZ delivery as a novel
      cardioprotective modality.

PMID- 28499887
TI  - What is the impact on the healthcare system if access to bariatric surgery is
      delayed?
AB  - BACKGROUND: Bariatric surgery has been available as part of the Brazilian Public
      Health System for patients with body mass index>40 kg/m2 (or>35 kg/m2 with co
      morbidities) since 1999. However, access to surgery is challenging, with eligible
      patients waiting up to 7 years before surgery. OBJECTIVE: Our objective was to
      compare costs and effectiveness of different waiting times before surgery versus
      prompt surgery. SETTINGS: Public practice. METHODS: A Markov microsimulation
      model compared 5 different strategies: no surgery, prompt surgery, and delaying
      surgery for 1, 2, 4, and 7 years. Markov tracker variables and states reflected
      changes in body mass index, type 2 diabetes status (including remission and
      relapse), and cardiovascular events. Time horizon was 20 years; discount rate,
      5%; and the perspective of the Brazilian Public Health System. Effectiveness was
      calculated as quality adjusted life years. RESULTS: Prompt surgery was the least
      costly and most effective strategy compared with any delay. Costs increased and
      effectiveness diminished progressively with the length of delays. Waiting 7 years
      for surgery was the most expensive and least effective strategy. Prompt surgery
      maintained dominance in 99.9%, 90.7%, 96.1%, and 94.2% of simulations in
      probabilistic sensitivity analyses versus 1-, 2-, 4-, and 7-year delays,
      respectively. Immediate surgery was very cost effective compared with no surgery
      in the case base. In the scenario with all patients having type 2 diabetes,
      immediate surgery was dominant to any strategy, including the no surgery group.
      CONCLUSIONS: Delaying bariatric operations is more expensive and less effective
      compared with prompt surgery and very cost effective compared with no surgery.
      Public health systems should pursue strategies to accelerate access to surgery to
      decrease obesity related complications and mortality of patients, but also to
      improve cost effectiveness.

PMID- 28499888
TI  - Almeria spatial memory recognition test (ASMRT): Gender differences emerged in a
      new passive spatial task.
AB  - Many different human spatial memory tasks were developed in the last two decades.
      Virtual reality based tasks make possible developing different scenarios and
      situations to assess spatial orientation but sometimes these tasks are complex
      for specific populations like children and older-adults. A new spatial task with
      a very limited technological requirement was developed in this study. It demanded
      the use of spatial memory for an accurate solution. It also proved to be
      sensitive to gender differences, with men outperforming women under high specific
      difficulty levels. Thanks to its simplicity it could be applied as a screening
      test and is easy to combine with EEG and fMRI studies.

PMID- 28499890
TI  - Interleukin-6 pathway blockade as an option for managing refractory cases of
      crystal arthritis: Two cases report.

PMID- 28499889
TI  - Recent advances in epilepsy genetics.
AB  - In last few years there has been rapid increase in the knowledge of epilepsy
      genetics. Nowadays, it is estimated that genetic epilepsies include over than 30%
      of all epilepsy syndromes. Several genetic tests are now available for diagnostic
      purposes in clinical practice. In particular, next-generation sequencing has
      proven to be effective in revealing gene mutations causing epilepsies in up to a
      third of the patients. This has lead also to functional studies that have given
      insight into disease pathophysiology and consequently to the identification of
      potential therapeutic targets opening the way of precision medicine for epilepsy
      patients. This minireview is focused on the most recent advances in genetics of
      epilepsies. We will also overview the modern genomic technologies and illustrate
      the diagnostic pathways in patients with genetic epilepsies. Finally, the
      potential implications for a personalized treatment (precision medicine) are also
      discussed.

PMID- 28499891
TI  - SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium (Cutibacterium) acnes.
AB  - Overt infection by Propionibacterium acnes is lacking in many SAPHO syndromes,
      and antibiotics have only a transient and incomplete effect, either in SAPHO
      syndrome or acne. As several auto-inflammatory bone disorders sharing
      overproduction of IL-1beta can mimic SAPHO, this syndrome could partly depend on
      genetically encoded overproduction of IL-1beta. However, cyclic intracellular
      infections, mostly by P. acnes, can contribute to the enhanced IL-1beta release
      by some skin cells, and probably by bone cells. P. acnes is indeed a powerful
      trigger of NLRP3-inflammasome activation and IL-1beta, leading to osteitis and
      enhanced mesenchymal cells differentiation in osteoblasts. Recent advances in the
      understanding of acne suggest that first steps of this disorder are not driven by
      P. acnes, but by a relative deficiency of FoxO1 within the nucleus of sebaceous
      cells. A similar defect of FoXO1 in bone cells should also be sought in SAPHO,
      since repression of FoxO1 gene is found in lesional psoriasis skin, and is
      associated with an increased number of osteoblasts and high bone mass in mice.
      FoxO1 selectively promotes IL-1beta production, so that its downregulation could
      help some P. acnes t escape innate immunity and persist in a latent state in bone
      cells, including mesenchymal stem cells. However, P. acnes itself possibly
      contributes to FoxO1 downregulation, like H. pylori infection which induces
      nuclear inactivation of FoxO1 in human gastric cells to slow down autophagic
      clearance. As bisphosphonates, which often improve SAPHO syndromes, enhance
      autophagy, it may be worth testing whether their combination with antibiotics is
      synergistic in SAPHO syndromes.

PMID- 28499892
TI  - Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive
      anterior ischemic optic neuropathy.
AB  - BACKGROUND: Giant cell arteritis is an inflammatory disorder of the medium- and
      large-size arteries. Permanent visual loss related to arteritic anterior ischemic
      optic neuropathy is among the most serious complications of this disease and
      initial treatment usually consists of high dose corticosteroids. There is no
      consensus in the literature concerning the optimal therapeutic approach in giant
      cell arteritis patients with corticosteroid-resistant arteritic anterior ischemic
      optic neuropathy. CASE REPORT: A 73-year-old Caucasian female with biopsy-proven
      giant cell arteritis developed an acute visual loss of the right eye due to
      arteritic anterior ischemic optic neuropathy. Despite 5 daily methylprednisolone
      pulses, systemic symptoms persisted and rapid involvement of the controlateral
      eye was documented. Therefore, tocilizumab (humanised monoclonal antibody binding
      the human interleukin-6 receptor) was introduced as a potential salvage therapy
      with a swift consecutive resolution of the systemic symptoms and stabilization of
      the ophthalmic lesions. CONCLUSIONS: Although a late effect of steroids pulses
      cannot be formally ruled out in this dramatic situation, tocilizumab likely
      offered a decisive effect in preventing bilateral blindness and may have
      contributed to steroid tapering. Tocilizumab may represent a new early effective
      second-line treatment option in corticosteroid-resistant anterior ischemic optic
      neuropathy. More data are needed to confirm this observation and to evaluate the
      safety profile of this treatment.

PMID- 28499893
TI  - Vertebroplasty and interventional radiology procedures for bone metastases.
AB  - Advances in cancer treatments have lengthened the survival of patients with bone
      metastases. Optimal control of the symptoms and prevention of the complications
      associated with bone metastases improve quality of life. Achieving these goals
      increasingly involves interventional radiology procedures. These include bone
      consolidation and analgesic techniques such as cementoplasty (vertebroplasty at
      the spine); percutaneous implantation of screws, metallic reinforcement devices,
      or intraosseous implants; and tumor destruction using thermal methods
      (radiofrequency and cryotherapy), chemicals (alcohol), and drugs
      (chemoembolization), which have fewer indications. Here, these techniques and
      their indications are reviewed.

PMID- 28499895
TI  - Epstein-Barr virus and rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, with a
      0.5% worldwide prevalence. The cause of RA remains unknown, however both genetic
      and environmental factors may contribute to its development. Among these is the
      Epstein-Barr virus (EBV). Here, we discuss several aspects of the close
      relationship between EBV and RA. Patients with RA have impaired control of EBV
      infection. Indeed, they have high titres of antibodies against EBV antigens.
      Their peripheral blood T lymphocytes are less efficient at controlling the
      outgrowth of EBV-infected B cells. RA patients have more EBV-infected B cells
      than normal controls, leading to a 10-fold systemic EBV overload. Post-transplant
      lymphoproliferative disorder (PTLPD) is a polyclonal EBV-positive B lymphocyte
      proliferation, which can evolve into an EBV-positive B cell lymphoma. RA patients
      also have an increased risk of developing EBV-associated lymphoproliferative
      disorder (LPD). Hence the need to monitor EBV load when treating RA patients with
      immunosuppressors. EBV, a widespread virus, highly recognized by antibodies but
      never eliminated, is an ideal candidate to trigger chronic immune complex
      disease. Anti-EBV antibody responses should be considered as one of the chronic
      autoantibody responses linked to the development of RA, in the same way as anti
      citrullinated protein antibodies.

PMID- 28499894
TI  - Pathophysiology of bone metastases from solid malignancies.
AB  - Bone metastases are common complications of many cancers. Among the mechanisms
      that set the scene for the development of bone metastases, several are shared by
      all forms of metastatic dissemination (pre-metastatic niche formation and
      chemotactic attraction of malignant cells, which invade the host tissue) and
      others are specific of bone tissue (homing of malignant cells to bone marrow
      niches and acquisition of an osteomimetic cell phenotype). After a latency period
      that can last several years, the malignant cells can proliferate into tumors that
      alter the normal bone remodeling process by inducing dysregulation of osteoblast
      and osteoclast function. These metastases may be lytic, characterized by major
      bone destruction; sclerotic, with excess bone formation; or mixed. Osteolysis
      occurs when the tumor cells stimulate osteoclast activity and inhibit osteoblast
      activity, whereas the opposite effects lead to bone sclerosis. Moreover, the
      mineralized bone matrix plays a major role in the formation of bone metastases,
      as its degradation releases growth factors and calcium that exert mitogenic
      effects on tumor cells. Thus, bone metastases are the site of a vicious circle in
      which mechanisms involved in bone resorption/formation promote tumor growth and
      vice versa.

PMID- 28499896
TI  - Decreased prefrontal brain activation during verbal fluency task in patients with
      somatoform pain disorder: An exploratory multi-channel near-infrared spectroscopy
      study.
AB  - BACKGROUND: Pain is a common phenomenon. Patients with somatoform pain disorder
      (SPD) suffer from lasting chronic pain which may cause cognitive impairment. The
      dysfunction of prefrontal cortex (PFC) may be involved in pain-induced cognition
      impairment, which is the most important part in regulating of cognitive function.
      Multi-channel near-infrared spectroscopy (NIRS) is a noninvasive and low-cost
      functional neuroimaging technique being used to detect the prefrontal cortex
      activation during cognitive tasks to demonstrate the relationship between PFC
      dysfunction and cognition impairment in SPD patients. METHODS: 24 patients with
      SPD and 24 age-, gender- and education level-matched healthy controls were
      examined by NIRS of the relative concentration of oxygenated hemoglobin (oxy-Hb)
      in PFC during verbal fluency task (VFT). All data analysis procedures were
      accomplished under MATLAB, SPM and SPM-fNIRS which is an SPM12-based software for
      fNIRS analysis. RESULTS: 1. The number of words generated during the VFT tasks in
      SPD patients were fewer than healthy controls. 2. The activated areas in SPD
      patients were smaller than healthy controls. 3. The average activation strength
      of [oxy-Hb] in SPD patients was much lower than healthy controls. 4. The
      difference of activation areas between left and right lobe were particularly
      obvious in SPD patients. CONCLUSION: There are evidences suggested that the
      markedly dysfunction in PFC especially bilateral dorsolateral prefrontal cortex
      (DLPFC) areas may be involved in the cognitive deficiency in patients with SPD.

PMID- 28499897
TI  - Reduced language lateralization in first episode schizophrenia: A near infrared
      spectroscopy study.
AB  - BACKGROUND: Diminished functional lateralization in language-related areas is
      found in chronic schizophrenia (SZ). However, whether this reduced lateralization
      exists at the early stage of SZ remains unclear. The present study aimed to
      investigate language lateralization in first episode schizophrenia (FES) using
      near infrared spectroscopy (NIRS) during a letter version of verbal fluency test
      (VFT). METHODS: A total of 28 FES patients and 33 healthy controls (HCs)
      underwent NIRS while performing a VFT. Six regions of interests (ROIs) were
      defined: the bilateral frontal-, inferior frontal gyrus (IFG), and temporal
      regions. Laterality index (LI) was calculated and compared between the two groups
      in ROIs. In addition, we investigated whether language lateralization was
      correlated with severity of clinical symptoms. RESULTS: Across all ROIs, LI was
      significantly reduced in FES patients (p=0.037) compared to controls in the IFG
      region. In addition, LI was not found to be correlated with VFT performance, the
      PANSS positive, negative or general psychopathology subscales. CONCLUSIONS: Our
      study demonstrated a diminution of leftward functional lateralization in the IFG
      during a VFT in FES patients. This is the first NIRS study to report reduced
      functional lateralization in patients at the early stage of schizophrenia.

PMID- 28499898
TI  - Antidepressant drugs for beta amyloid-induced depression: A new standpoint?
AB  - Mounting evidence suggests that depression represents a risk factor and an early
      manifestation of Alzheimer's disease (AD). Neuropsychiatric symptoms may derive
      from neurobiological changes in specific brain areas and may be considered
      prodromal of dementia. We have previously reported the depressive-like profile in
      rats receiving a single intracerebroventricular injection of soluble amyloid beta
      protein (betaA). Here, we verified the effect of different classes of
      antidepressants on the betaA-induced depressive behavior and on cortical
      monoamine levels. To these purposes, the forced swimming test was performed and
      cortical levels of serotonin (5-HT) and noradrenaline (NA) were quantified by
      high performance liquid chromatography (HPLC). We found that acute fluoxetine
      (20mg/kg, s.c.), reboxetine (10mg/kg, s.c.), and ketamine (15mg/kg, i.p.)
      significantly reduced the immobility in betaA-treated rats compared to controls.
      Fluoxetine and reboxetine reversed 5-HT reduction, while betaA-induced NA
      increase was further enhanced by all treatments. Treatments with fluoxetine,
      reboxetine and ketamine were able to revert soluble betaA-induced decrease of
      cortical BDNF levels, while only fluoxetine and ketamine, but not reboxetine, had
      the same effects on cortical NGF expression. Moreover, plasma soluble betaA
      levels were lowered by fluoxetine, but not reboxetine and ketamine, treatments.
      Our data suggest that different classes of antidepressants yield a short-acting
      effect on rat soluble betaA-induced depressive profile. Thus, we hypothesize a
      novel common mechanism of action of these drugs also based upon a "betaA
      lowering" effect. Although further investigations are still needed, our study
      might open a new scenario for unravelling the molecular antidepressant mechanisms
      of these drugs.

PMID- 28499899
TI  - The wake-promoting drug Modafinil prevents motor impairment in sickness behavior
      induced by LPS in mice: Role for dopaminergic D1 receptor.
AB  - The wake-promoting drug Modafinil has been used for many years for treatment of
      Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related
      psychostimulant action. Recent studies have indicated that Modafinil prevents
      neuroinflammation in animal models. Thus, the aim of the present study was to
      evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)
      induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were
      pretreated with Vehicle or Modafinil (90mg/Kg) and, 30min later, received a
      single saline or LPS (2mg/Kg) administration, and were submitted to the open
      field and elevated plus maze test 2h later. After 24h, mice were subjected to
      tail suspension test, followed by either flow cytometry with whole brain for
      CD11b+CD45+ cells or qPCR in brain areas for cytokine gene expression. Modafinil
      treatment prevented the LPS-induced motor impairment, anxiety-like and depressive
      like behaviors, as well as the increase in brain CD11b+CD45high cells induced by
      LPS. Our results indicate that Modafinil pretreatment also decreased the IL-1beta
      gene upregulation caused by LPS in brain areas, which is possibly correlated with
      the preventive behavioral effects. The pharmacological blockage of the
      dopaminergic D1R by the drug SCH-23390 counteracted the effect of Modafinil on
      locomotion and anxiety-like behavior, but not on depressive-like behavior and
      brain immune cells. The dopaminergic D1 receptor signaling is essential to the
      Modafinil effects on LPS-induced alterations in locomotion and anxiety, but not
      on depression and brain macrophages. This evidence suggests that Modafinil
      treatment might be useful to prevent inflammation-related behavioral alterations,
      possibly due to a neuroimmune mechanism.

PMID- 28499900
TI  - Lurasidone in post-menopausal females with major depressive disorder with mixed
      features: Post-hoc analysis of a placebo-controlled trial.
AB  - BACKGROUND: Several studies have found that depressed, post-menopausal females
      may respond differently to antidepressants compared to pre-menopausal females.
      The atypical antipsychotic lurasidone, whose mechanism of action differs from
      SSRIs and other standard antidepressants, was shown in a 6-week randomized,
      flexible-dose, placebo-controlled study (n=209), to be effective in treating
      major depressive disorder (MDD) with mixed features (subthreshold hypomanic
      symptoms). This post-hoc analysis assessed the efficacy of lurasidone in this
      study by menopausal status. METHODS: The main outcome measure for this post-hoc
      analysis was change in MADRS score from baseline to week 6 endpoint for two
      lurasidone-treated subgroups: presumptive pre-menopausal (<52years) and
      presumptive post-menopausal (>=52years) patients, compared to placebo treatment,
      using a mixed-model for repeated-measures analysis, and calculation of the effect
      size for each subgroup. Additional efficacy assessments included the CGI-S, HAM-A
      and YMRS. An exploratory analysis was also conducted removing presumptive peri
      menopausal women (ages 45-51years) to allow for clearer definition of pre- and
      post-menopausal status. RESULTS: A total of 56 lurasidone-treated and 47 placebo
      treated pre-menopausal females, and 17 lurasidone-treated and 25 placebo-treated
      post-menopausal females were available from the larger study for comparison on
      key outcome measures. The pre- and post-menopausal subgroups had similar
      demographic and clinical characteristics at study baseline (other than age),
      including number of past major depressive episodes as well as depressive and
      manic symptom severity. Mean daily lurasidone dose was similar for each subgroup
      during the study. Both the primary and exploratory analyses showed that both
      lurasidone-treated post-menopausal and pre-menopausal females responded
      significantly compared to placebo (p=0.016 or less) on the MADRS, and that post
      menopausal patients had a numerically larger response (effect size=0.96) than pre
      menopausal patients (effect size=0.64). All other secondary outcome measures for
      lurasidone compared with placebo treatment were significant (p=0.045 or less) for
      both subgroups. CONCLUSIONS: In this post-hoc analysis, lurasidone was found to
      be effective in treating post-menopausal MDD patients with mixed features
      (subthreshold hypomanic symptoms).

PMID- 28499901
TI  - Antioxidant and anti-inflammatory nutrient status, supplementation, and
      mechanisms in patients with schizophrenia.
AB  - Over 50 million people around the world suffer from schizophrenia, a severe
      mental illness characterized by misinterpretation of reality. Although the exact
      causes of schizophrenia are still unknown, studies have indicated that
      inflammation and oxidative stress may play an important role in the etiology of
      the disease. Pro-inflammatory cytokines are crucial for normal central nervous
      development and proper functioning of neural networks and neurotransmitters.
      Patients with schizophrenia tend to have abnormal immune activation resulting in
      elevated pro-inflammatory cytokine levels, ultimately leading to functional brain
      impairments. Patients with schizophrenia have also been found to suffer from
      oxidative stress, a result of an imbalance between the production of free
      radicals and the ability to detoxify their harmful effects. Furthermore,
      inflammation and oxidative stress are implicated to be related to the severity of
      psychotic symptoms. Several nutrients are known to have anti-inflammatory and
      antioxidant functions through various mechanisms in our body. The present review
      evaluates studies and literature that address the status and supplementation of
      omega-3 polyunsaturated fatty acids, vitamin D, B vitamins (B6, folate, B12),
      vitamin E, and carotenoids in different stages of schizophrenia. The possible
      anti-inflammatory and antioxidant mechanisms of action of each nutrient are
      discussed.

PMID- 28499902
TI  - Dumbbell-Shaped Jugular Foramen Tumors Extending to the Neck: Surgical
      Considerations Based on Imaging Findings.
AB  - OBJECTIVE: Dumbbell-shaped jugular foramen tumors (DSJFTs) extending to the neck
      present diagnostic and management difficulties because of their rarity, various
      pathologies, and multidisciplinary involvement. Accurate imaging findings are of
      great importance for surgical planning and clinical outcomes. However, few
      articles have discussed this issue to date. METHODS: Thirty-one patients with
      DSJFTs extending to the neck were surgically treated in a single stage at our
      institute. Their clinical and radiologic features, operative procedures, and
      outcomes were retrospectively reviewed. RESULTS: Preoperative correct diagnosis
      of DSJFTs extending to the neck was made in all cases of benign tumor and in only
      3 cases of malignant tumors in this series. All tumors were removed via a
      craniocervical approach by a multidisciplinary skull base team because of both
      their intracranial and neck extensions. Total removal was achieved in 26 patients
      (83.9%). Preoperative symptoms were improved in 18 patients, whereas new or
      worsening lower cranial nerve deficits occurred in 4 patients postoperatively.
      Follow-up (1-132 months, mean 64.4 months) was available in 90.3% of the
      patients. No clinical or radiologic signs of tumor recurrence were observed.
      CONCLUSIONS: Preoperative radiologic evaluation of DSJFTs extending to the neck
      is essential for differential diagnosis, patient selection, and surgical
      planning. Favorable surgical outcomes can be achieved via a craniocervical
      approach, and some detailed imaging findings are helpful to increase the safety
      of tumor resection and reduce the morbidity of lower cranial nerve deficits and
      cerebrospinal fluid leakage.

PMID- 28499903
TI  - Use of Paine's Technique: Projecting Puncture Point to the Skull and Skin.
AB  - OBJECTIVE: Ventriculostomy from Paine's point is an effective technique to ensure
      that the brain is relaxed for aneurysm surgery. This study aimed to use Paine's
      point for other neurosurgical procedures (except for those that require a
      pterional approach) by delineation of surface landmarks for identification of
      Paine's point on the cranium and scalp. METHODS: Based on the anatomical
      knowledge and examination of 3-dimensional computed tomography images of skull,
      we determined novel surface landmarks to identify Paine's point on the cranium
      and scalp. The new method was used in patients with intraventricular hemorrhage
      and aneurysmal subarachnoid hemorrhage caused by ruptured aneurysm of the
      anterior communicating artery. RESULTS: The puncture point was determined at a
      point located 2.5 cm superior to the supraorbital margin on linea temporalis on
      the skull and 2.5 cm superior to the eyebrow along the anterior edge of temporal
      muscle on the skin. Ventriculostomy was performed from Paine's point in patients
      with intraventricular hemorrhage or aneurysmal subarachnoid hemorrhage who
      underwent aneurysm surgery via an interhemispheric approach. No adverse events
      were observed in any of the patients. CONCLUSIONS: By accurate surface marking on
      skull and skin, the use of Paine's point for ventriculostomy performed via an
      interhemispheric approach or for simple burr-hole surgery was found to be safe
      and reliable.

PMID- 28499904
TI  - Completely Thrombosed Distal Middle Cerebral Artery Aneurysm Mimicking a
      Cavernous Angioma: Case Report and Review of the Literature.
AB  - BACKGROUND: Distal middle cerebral artery (MCA) aneurysms originate from branches
      of MCA distal to its main bifurcation or the peripheral branches. Distal MCA
      aneurysms are uncommon compared with saccular aneurysms, which develop along the
      proximal trunks of MCA. However, thrombotic aneurysms, characterized by organized
      intraluminal thrombus and solid mass, are frequently in the large and giant size
      range, whereas complete thrombosis of non-giant MCA aneurysms is very rare. CASE
      PRESENTATION: We present the clinical case of a 53 years-old woman with a
      completely thrombosed medium distal MCA aneurysm mimicking a cavernous angioma.
      She came to our emergency department after the onset of tinnitus and persistent
      headache. Magnetic resonance imaging performed subsequently showed a nodular mass
      surrounded by edema located in the temporal lobe with a homogeneous peripheral
      contrast enhancement. Furthermore, angiography showed regular flow in the MCA and
      confirmed the diagnosis of cavernous angioma. The patient underwent surgery, and
      the lesion was found to be a thrombosed aneurysm originating from the distal
      temporal branch of the left MCA (M2 segment). CONCLUSIONS: To our knowledge, this
      is the first report of a thrombosed distal medium MCA aneurysm that mimicked a
      cavernous angioma. The completely thrombosed aneurysm can be confused with
      intracranial lesions or cavernous malformations, which can have similar
      radiographic features without angiographic anomalies, so it is mandatory to
      consider the possibility of a thrombosed aneurysm for a correct differential
      diagnosis.

PMID- 28499905
TI  - Unholy Alliance, Pathway to Scholarly Work, or Just an Association?

PMID- 28499906
TI  - A numerical approach to determine mutant invasion fitness and evolutionary
      singular strategies.
AB  - We propose a numerical approach to study the invasion fitness of a mutant and to
      determine evolutionary singular strategies in evolutionary structured models in
      which the competitive exclusion principle holds. Our approach is based on a dual
      representation, which consists of the modeling of the small size mutant
      population by a stochastic model and the computation of its corresponding
      deterministic model. The use of the deterministic model greatly facilitates the
      numerical determination of the feasibility of invasion as well as the convergence
      stability of the evolutionary singular strategy. Our approach combines standard
      adaptive dynamics with the link between the mutant survival criterion in the
      stochastic model and the sign of the eigenvalue in the corresponding
      deterministic model. We present our method in the context of a mass-structured
      individual-based chemostat model. We exploit a previously derived mathematical
      relationship between stochastic and deterministic representations of the mutant
      population in the chemostat model to derive a general numerical method for
      analyzing the invasion fitness in the stochastic models. Our method can be
      applied to the broad class of evolutionary models for which a link between the
      stochastic and deterministic invasion fitnesses can be established.

PMID- 28499907
TI  - Occurrence of ampicillin-resistant Enterococcus faecium carrying esp gene in pet
      animals: An upcoming threat for pet lovers.
AB  - OBJECTIVES: This study was carried out to investigate oral colonisation by
      Enterococcus faecalis and Enterococcus faecium in pet dogs and cats, with special
      reference to antibiotic resistance. METHODS: Oral swabs were collected from 63
      pet dogs and 57 pet cats with no known history of hospitalisation. All samples
      were enriched in Kenner Fecal (KF) broth before being cultured on KF agar to
      isolate enterococci. E. faecalis and E. faecium were identified by biochemical
      and molecular techniques. Antimicrobial resistance was determined by the disk
      diffusion method, and ampicillin-resistant strains were further examined by PCR
      to detect the esp gene. RESULTS: Oral prevalence rates of E. faecalis among pet
      dogs and cats were 3.2% and 5.3%, respectively, whilst those for E. faecium were
      22.2% and 15.8%, respectively. None of the isolated enterococci were resistant to
      vancomycin. However, ampicillin-resistant E. faecium (AREfm) was detected in the
      examined dogs and cats at rates of 14.3% and 5.3%, respectively. Moreover, among
      the isolated enterococci, six isolates showed multidrug resistance (all AREfm).
      Whilst the esp gene was detected in only two of nine canine AREfm isolates
      (multidrug-resistant strains), none of feline AREfm isolates harboured esp.
      CONCLUSIONS: The occurrence of AREfm and the esp gene among oral isolates from
      pet dogs and cats represents a great public health hazard for pet owners and
      highlights possible zoonotic transmission of such a nosocomial pathogen outside
      healthcare facilities.

PMID- 28499908
TI  - Identification of novel mammalian hosts and Brazilian biome geographic
      distribution of Trypanosoma cruzi TcIII and TcIV.
AB  - Trypanosoma cruzi is a parasitic protozoan responsible for Chagas disease. Seven
      different Discrete Typing Units (DTUs) of T. cruzi are currently identified in
      nature: TcI-TcVI, and TcBat whose distribution patterns in nature,
      hosts/reservoirs and eco-epidemiological importance are still little known. Here,
      we present novel data on the geographic distribution and diversity of mammalian
      hosts and vectors of T. cruzi DTUs TcIII and TcIV. In this study, we analyzed 61
      T. cruzi isolates obtained from 18 species of mammals (five orders) and two
      Hemiptera genera. Samples were collected from five Brazilian biomes (Pantanal,
      Caatinga, Cerrado, Atlantic Rainforest, and Amazon) previously characterized as
      Z3 or mixed infection (TcI-Z3) by mini-exon gene PCR. To identify TcIII and TcIV
      genotypes, we applied restriction fragment length polymorphism analysis to the
      PCR-amplified histone 3 gene. DTUs TcIII and TcIV were identified in single and
      mixed infections from wide dispersion throughout five Brazilian biomes studied,
      with TcIV being the most common. Pantanal was the biome that displayed the
      largest number of samples characterized as TcIII and TcIV in single and mixed
      infections, followed by Atlantic Rainforest and Amazon. Species from the
      Didelphimorphia order displayed the highest frequency of infection and were found
      in all five biomes. We report, for the first time, the infection of a species of
      the Artiodactyla order by DTU TcIII. In addition, we describe new host species:
      five mammals (marsupials and rodents) and two genera of Hemiptera. Our data
      indicate that DTUs TcIII and TcIV are more widespread and infect a larger number
      of mammalian species than previously thought. In addition, they are transmitted
      in restricted foci and cycles, but in different microhabitats and areas with
      distinct ecological profiles. Finally, we show that DTUs TcIII and TcIV do not
      present any specific association with biomes or host species.

PMID- 28499909
TI  - Sesame oil: An ex vivo study of properties against oxidation of plasma low
      density lipoproteins and total serum lipoproteins.

PMID- 28499910
TI  - SPARC paucity alleviates superoxide-mediated oxidative stress, apoptosis, and
      autophagy in diabetogenic hepatocytes.
AB  - Secreted protein acidic and rich in cysteine (SPARC) is known to play a
      previously unappreciated role in diabetes, but its precise mechanism in
      liver/hepatocyte pathology remains unknown. Inhibition of SPARC is critical in
      resolving candidate pathogenic events such as production of reactive oxygen
      species (ROS), which are broadly considered for their roles in diabetes, and is
      capable of protecting functional hepatocytes. Here, we provide in vitro and in
      vivo evidence demonstrating pathological correlations between SPARC and
      streptozotocin (STZ)-induced diabetic rat livers as well as cultured hepatocytes
      induced by diabetogenic stimuli. Under these conditions, transient SPARC
      silencing was carried out to investigate the role of SPARC in the pathogenesis of
      pro-diabetic hepatocyte damage and dysfunction. The constitutive expression of
      SPARC in hepatocytes was up-regulated under a diabetic environment. In addition,
      Nox4-dependent superoxide generation contributed to increased expression of
      SPARC, and this was inhibited by tiron and pharmacological or genetic
      inactivation of Nox4-containing NADPH oxidase. Remarkably, SPARC deficiency
      inhibited diabetic stimuli-induced elevation of superoxide production and
      resolved salient features of hepatocyte damage such as impaired cytoprotection,
      inflammation, apoptosis, and autophagy. At the same time, links between SPARC,
      integrin-beta1, Nox4-derived superoxide, and JNK signaling provide a basis for
      these phenotypes. Taken together with the observations that SPARC deficiency had
      protective effects on hepatocytes via a favorable inhibition profile, functional
      knowledge of SPARC may offer a unique therapeutic approach to preserve
      hepatocellular fate decisions in diabetes.

PMID- 28499911
TI  - Aging-associated metabolic disorder induces Nox2 activation and oxidative damage
      of endothelial function.
AB  - Oxidative stress attributable to the activation of a Nox2-containing NADPH
      oxidase is involved in the development of vascular diseases and in aging.
      However, the mechanism of Nox2 activation in normal aging remains unclear. In
      this study, we used age-matched wild-type (WT) and Nox2 knockout (KO) mice at 3-4
      months (young); 11-12 months (middle-aged) and 21-22 months (aging) to
      investigate age-related metabolic disorders, Nox2 activation and endothelial
      dysfunction. Compared to young mice, middle-aged and aging WT mice had
      significant hyperglycaemia, hyperinsulinaemia, increased systemic oxidative
      stress and higher blood pressure. Endothelium-dependent vessel relaxation to
      acetylcholine was significantly impaired in WT aging aortas, and this was
      accompanied by increased Nox2 and ICAM-1 expressions, MAPK activation and
      decreased insulin receptor expression and signaling. However, these aging
      associated disorders were significantly reduced or absent in Nox2KO aging mice.
      The effect of metabolic disorder on Nox2 activation and endothelial dysfunction
      was further confirmed using high-fat diet-induced obesity and insulin resistance
      in middle-aged WT mice treated with apocynin (a Nox2 inhibitor). In vitro
      experiments showed that in response to high glucose plus high insulin challenge,
      WT coronary microvascular endothelial cells increased significantly the levels of
      Nox2 expression, activation of stress signaling pathways and the cells were
      senescent, e.g. increased p53 and beta-galactosidase activity. However, these
      changes were absent in Nox2KO cells. In conclusion, Nox2 activation in response
      to aging-associated hyperglycaemia and hyperinsulinaemia plays a key role in the
      oxidative damage of vascular function. Inhibition or knockout of Nox2 preserves
      endothelial function and improves global metabolism in old age.

PMID- 28499912
TI  - Cyclophosphamide and acrolein induced oxidative stress leading to deterioration
      of metaphase II mouse oocyte quality.
AB  - Cyclophosphamide (CTX) is a chemotherapeutic agent widely used to treat ovarian,
      breast, and hematological cancers as well as autoimmune disorders. Such
      chemotherapy is associated with reproductive failure and premature ovarian
      insufficiency. The mechanism by which CTX and/or its main metabolite, acrolein,
      affect female fertility remains unclear, but it is thought to be caused by an
      overproduction of reactive oxygen species (ROS). Here, we investigated the effect
      of CTX on metaphase II mouse oocytes obtained from treated animals (120mg/kg, 24h
      of single treatment), and oocytes directly exposed to increasing concentrations
      of CTX and acrolein (n=480; 0, 5, 10, 25, 50, and 100MUM) with and without
      cumulus cells (CCs) for 45min which correlates to the time of maximum peak plasma
      concentrations after administration. Oocytes were fixed and subjected to indirect
      immunofluorescence and were scored based on microtubule spindle structure (MT)
      and chromosomal alignment (CH). Generation of ROS was evaluated using the
      Cellular Reactive Oxygen Species Detection Assay Kit. Deterioration of oocyte
      quality was noted when oocytes were obtained from CTX treated mice along with CTX
      and acrolein treated oocytes in a dose-dependent manner as shown by an increase
      in poor scores. Acrolein had an impact at a significantly lower level as compared
      to CTX, plateau at 10MUM versus 50MUM, respectively. These variation is are
      associated with the higher amount of ROS generated with acrolein exposure as
      compared to CTX (p<0.05). Utilization of antioxidant therapy and acrolein
      scavengers may mitigate the damaging effects of these compounds and help women
      undergoing such treatment.

PMID- 28499913
TI  - Integration of gel-based and gel-free proteomic data for functional analysis of
      proteins through Soybean Proteome Database.
AB  - : The Soybean Proteome Database (SPD) stores data on soybean proteins obtained
      with gel-based and gel-free proteomic techniques. The database was constructed to
      provide information on proteins for functional analyses. The majority of the data
      is focused on soybean (Glycine max 'Enrei'). The growth and yield of soybean are
      strongly affected by environmental stresses such as flooding. The database was
      originally constructed using data on soybean proteins separated by two
      dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic
      technique. Since 2015, the database has been expanded to incorporate data
      obtained by label-free mass spectrometry-based quantitative proteomics, which is
      a gel-free proteomic technique. Here, the portions of the database consisting of
      gel-free proteomic data are described. The gel-free proteomic database contains
      39,212 proteins identified in 63 sample sets, such as temporal and organ-specific
      samples of soybean plants grown under flooding stress or non-stressed conditions.
      In addition, data on organellar proteins identified in mitochondria, nuclei, and
      endoplasmic reticulum are stored. Furthermore, the database integrates multiple
      omics data such as genomics, transcriptomics, metabolomics, and proteomics. The
      SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. BIOLOGICAL
      SIGNIFICANCE: The Soybean Proteome Database stores data obtained from both gel
      based and gel-free proteomic techniques. The gel-free proteomic database
      comprises 39,212 proteins identified in 63 sample sets, such as different organs
      of soybean plants grown under flooding stress or non-stressed conditions in a
      time-dependent manner. In addition, organellar proteins identified in
      mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free
      proteomics database. A total of 44,704 proteins, including 5490 proteins
      identified using a gel-based proteomic technique, are stored in the SPD. It
      accounts for approximately 80% of all predicted proteins from genome sequences,
      though there are over lapped proteins. Based on the demonstrated application of
      data stored in the database for functional analyses, it is suggested that these
      data will be useful for analyses of biological mechanisms in soybean.
      Furthermore, coupled with recent advances in information and communication
      technology, the usefulness of this database would increase in the analyses of
      biological mechanisms.

PMID- 28499914
TI  - Advances in understanding the pathophysiology of autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental
      disorders with typical triad of symptoms: impaired social interaction, language
      and communication abnormalities and stereotypical behavior. Despite extensive
      research, the etiology and pathogenesis of ASD remain largely unclear. The lack
      of solid knowledge on the mechanisms of these disorders decreases the
      opportunities for pathogenetic treatment of autism. Various theories where
      proposed in order to explain the pathophysiology underlying ASD. Despite the fact
      that none of them is able to completely explain the impairments in the nervous
      system of ASD patients, these hypotheses were instrumental in highlighting the
      most important mechanisms in the development of this complex disorder. Some new
      theories are based on neurovisualization studies, others on the data from genomic
      studies, which become increasingly available worldwide. As the research in this
      field is largely dependent on the animal models, there is an ongoing discussion
      and search for the most appropriate one adequately reproducing the pathology.
      Here we provide an overview of current theories of the origin and development of
      ASD discussed in the context of existing and proposed rodent models of ASD.

PMID- 28499915
TI  - Early life stress and later peer distress on depressive behavior in adolescent
      female rats: Effects of a novel intervention on GABA and D2 receptors.
AB  - Early life adversity (ELA) increases the risk of depression during adolescence
      that may result from a decline in parvalbumin (PVB) secondary to increased
      neuroinflammation. In this study, we investigated depressive-like behavior
      following exposure to two different types of stressors that are relevant for
      their developmental period: 1) chronic ELA (maternal separation; MS) and 2) an
      acute emotional stressor during adolescence (witnessing their peers receive
      multiple shocks; WIT), and their interaction. We also determined whether reducing
      inflammation by cyclooxygenase-2 (COX-2) inhibition would prevent the onset of
      depressive-like behavior. Female Sprague-Dawley rat pups underwent MS for four
      hours/day or received typical care (CON) between postnatal days (P) 2 and P20. A
      COX-2 inhibitor (COX-2I) or vehicle was administered every other day between P30
      and P38. Subjects were tested for learned helplessness to assess depressive-like
      behavior at P40 (adolescence). MS females demonstrated increased escape latency
      and decreased PVB in the prefrontal cortex (PFC) and dorsal raphe that were
      attenuated by COX-2I intervention. Helplessness was also associated with an
      increase in D2 receptors in the accumbens. In contrast, WIT elevated escape
      latency in CON, but reduced latency in MS females. Furthermore, COX-2I
      intervention decreased escape latency in both CON and MS after WIT. WIT reduced
      PVB levels in the basolateral amygdala and increased PFC levels to CON levels.
      Our data suggest that decreased PVB in the PFC is important for the expression of
      depressive-like behavior and suggest that COX-2I intervention may provide a novel
      prevention for depression.

PMID- 28499916
TI  - Effects of neonatal and adolescent neuroactive steroid manipulation on locomotor
      activity induced by ethanol in male wistar rats.
AB  - Neonatal neuroactive steroids levels are crucial for brain development.
      Alterations of neonatal neuroactive steroids levels induce anxiolytic-like
      effects and improve exploration in novel environments in adulthood. These
      behavioural traits, i.e. sensation/novelty seeking, anxiety or impulsivity, are
      associated with vulnerability to drug use and abuse. Adolescence is also
      recognized as a particularly critical developmental phase to contribute to
      vulnerable phenotype. However, the influence of neuroactive steroids during
      development in the vulnerability to drug addiction has been poorly studied. The
      aim of the present experiment is to study the effect of early neonatal and
      adolescent manipulations of neuroactive steroids on the sensitivity to the
      stimulant effects of ethanol in adult male rats. Therefore, allopregnanolone or
      finasteride, an allopregnanolone synthesis inhibitor, were injected from
      postnatal day 5-9. In early adolescence, half of the subjects were injected with
      progesterone, the main allopregnanolone precursor, and the elevated plus-maze
      anxiety test was performed. Results indicated that early adolescent progesterone
      induced anxiolytic-like effects (increase in the percentage of entries and time
      in open arms). Neonatal finasteride administration decreased locomotor activity
      induced by ethanol in adolescent vehicle subjects. Interestingly, differences
      induced by neonatal treatments were not present in the animals that received
      progesterone in the early adolescence. In conclusion, neuroactive steroid
      manipulations in crucial stages of development could be playing an important role
      in behavioural effects of alcohol such as the sensitivity to locomotor
      stimulation.

PMID- 28499917
TI  - The role of matrix metalloproteinases in aging: Tissue remodeling and beyond.
AB  - Proteases are a set of enzymes that have been involved in multiple biological
      processes throughout evolution. Among them, extracellular matrix (ECM) remodeling
      has emerged as one of the most relevant functions exerted by these proteins,
      being essential in the regulation of critical events such as embryonic
      development or tissue homeostasis. Hence, it is not surprising that dysregulation
      in any protease function that affects ECM homeostasis may contribute to the aging
      process. Matrix metalloproteinases (MMPs) are one of the most important families
      of proteases involved in the tight control of ECM remodeling over time. In this
      review, we will discuss how MMPs and other proteases alter ECM composition and
      mechanical properties in aging, thereby affecting stem cell niches and the
      development of senescent phenotypes. Finally, we will summarize recent findings
      that associate MMPs with the development of age-related diseases, such as
      neurodegenerative disorders.

PMID- 28499918
TI  - Cul3 neddylation is crucial for gradual lipid droplet formation during
      adipogenesis.
AB  - Cullin 3 (Cul3) belongs to the family of cullins (Cul1-7) providing the scaffold
      for cullin-RING ubiquitin (Ub) ligases (CRLs), which are activated by neddylation
      and represent essential E3 ligases of the Ub proteasome system. During adipogenic
      differentiation neddylated Cul3 accumulates in LiSa-2 preadipocytes.
      Downregulation of Cul3 and inhibition of neddylation by MLN4924 blocks the
      formation of lipid droplets (LDs), the lipid storage organelles and markers of
      adipogenesis. Neddylation of Cul3 coincides with an increase of Rab18, a GTPase
      associated with LDs. Immunoprecipitation and confocal fluorescence microscopy
      revealed physical association of Cul3 and Rab18 at the membrane of LDs. RhoA, a
      suppressor of adipogenesis decreased during differentiation. Our results in LiSa
      2 cells, but also mouse embryonic fibroblasts revealed a connection between Cul3,
      Rab18 and RhoA. Downregulation of Cul3 led to a marked increase in RhoA protein
      expression after 6days of LiSa-2 cell differentiation, suggesting that Cul3 is
      involved in the regulation of RhoA stability.

PMID- 28499920
TI  - Patient Understanding, Expectations, and Satisfaction Regarding Rotator Cuff
      Injuries and Surgical Management.
AB  - Rotator cuff injuries are among the most common in orthopaedics, with rotator
      cuff repair surgery consistently reported as one of the most commonly performed
      orthopaedic procedures. Patient satisfaction is becoming an increasingly
      important outcome metric as health care continues to evolve with regard to
      quality measures affecting physician reimbursement. Evidence supports that
      postoperative patient satisfaction, an important quality outcome metric, is
      highly influenced by preoperative patient expectations, which are in turn
      governed by patient knowledge and understanding. Many authors have delineated
      patient-, injury-, and surgery-specific variables associated with high
      preoperative expectations and satisfaction after rotator cuff surgery.
      Specifically, large rotator cuff tears, subscapularis tears, persistence of
      postoperative pain and dysfunction, worker's compensation cases, lower education
      level, and preoperative disability have been seen more frequently in patients
      reporting poor satisfaction. Others have reported variables associated with
      higher patient satisfaction such as being married, employed, and of older age at
      the time of surgery (>55 years old) predictive of higher satisfaction. Patient
      education preoperatively regarding details about the surgery and the
      postoperative plan both immediately after the procedure and for rehabilitation
      are critical in helping set patients' preoperative expectations that have a known
      effect on patients' subjective clinical outcomes.

PMID- 28499919
TI  - Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by
      reducing autophagy.
AB  - Malignant glioma is an aggressive brain cancer that responds poorly to
      chemotherapy. However, the molecular mechanism underlying the development of
      chemoresistance in glioma is not well-understood. In this study, we show that
      long non-coding RNA AC023115.3 is induced by cisplatin in human glioblastoma
      cells and that elevated AC023115.3 promotes cisplatin-induced apoptosis by
      inhibiting autophagy. Further mechanistic studies revealed that AC023115.3 acts
      as a competing endogenous RNA for miR-26a and attenuates the inhibitory effect of
      miR-26a on GSK3beta, a proline-directed serine-threonine kinase that promotes the
      degradation of Mcl1, leading to an increase in GSK3beta and a decrease in
      autophagy. Additionally, we discovered that AC023115.3 improves chemosensitivity
      of glioma cells to cisplatin by regulating the miR-26a-GSK3beta-Mcl1 pathway.
      Thus, these data indicate that the AC023115.3-miR-26a-GSK3beta signalling axis
      plays an important role in reducing the chemoresistance of glioma.

PMID- 28499921
TI  - Anterior Cruciate Ligament Soft Tissue Graft Fixation in the Elderly: Is There a
      Reason to Use Interference Screws? A Human Cadaver Study.
AB  - PURPOSE: To analyze the ultimate failure load, yield load, stiffness, and cyclic
      resistance of different anterior cruciate ligament (ACL) soft tissue graft
      fixation techniques in osteopenic bone. METHODS: In this study, 24 fresh-frozen
      human cadaveric tibiae (mean age 82.6 years; range 56-96; 6 male and 6 female
      donors) were used. Quantitative computed tomography was performed to match bone
      density. Looped porcine flexor tendon grafts were chosen as ACL graft substitutes
      for tibial graft fixation techniques (n = 8 each): (1) hybrid fixation with an
      interference screw and extracortical button fixation; (2) extracortical button
      fixation; and (3) interference screw fixation. In single cycle mode, constructs
      were loaded to failure to evaluate stiffness, yield load, and maximum load. In
      cyclic testing, 2,000 cycles (25-100 N) were applied followed by loading to
      failure. A 1-way analysis of variance was performed with significance set at P =
      .05. RESULTS: Hybrid fixation resulted in significantly higher yield load (283.4
      +/- 86.19 N; P = .0037) and maximum load (407.9 +/- 102.3 N; P = .0026) than
      interference screw fixation (yield load 176.4 +/- 26.03, max load 231.8 +/- 94.06
      N) in elderly bone. Yield load after extracortical button fixation (252.9 +/-
      41.97 N; P = .0286) was also higher than that after interference screw fixation,
      but stiffness (18.98 +/- 9.154 N/mm; P = .0041) was less than that after hybrid
      fixation (37.28 +/- 13.53 N/mm). Of 8 specimens in the interference screw group,
      7 did not survive 2,000 cycles and failed by graft slippage, whereas all other
      specimens in both other groups survived. CONCLUSIONS: Tibial hybrid fixation of
      ACL soft tissue grafts provides less vertical graft movement than extracortical
      button fixation and higher primary failure loads than interference screw fixation
      in elderly bone. CLINICAL RELEVANCE: In this elderly human joint in vitro model,
      tibial hybrid fixation provides biomechanical advantages over other techniques.
      Graft fixation with only an interference screw should be avoided in osteopenic
      bone.

PMID- 28499922
TI  - Critical Analysis of the Lever Test for Diagnosis of Anterior Cruciate Ligament
      Insufficiency.
AB  - PURPOSE: To critically analyze the "lever test" in detecting anterior cruciate
      ligament (ACL) tears and to compare its accuracy with the Lachman, anterior
      drawer (AD), and pivot shift tests. METHODS: From June 2014 to June 2015, 91
      subjects were analyzed. Inclusion criteria were subjects aged 16 to 60 years,
      presenting after a knee injury with subjective swelling, or an objective effusion
      and an uninjured normal contralateral knee for comparison. Exclusion criteria
      included previous knee ligamentous reconstruction, fracture of the distal femur
      or proximal tibia, bilateral knee injuries, or known cruciate ligament tear. The
      Lachman, AD, pivot shift, and lever tests were performed in the office by 2 board
      certified orthopaedic surgeons with patient awake. Examiners were blinded to the
      presence or absence of ACL injury. Magnetic resonance imaging was used to
      determine injury. Sensitivity, specificity, and accuracy were evaluated for all 4
      tests. Accuracy was compared using chi-square and receiver operator curves.
      RESULTS: Average subject age was 28 +/- 11 years (61 males, 30 females). Seventy
      one (79%) had ACL tears diagnosed by magnetic resonance imaging. The sensitivity,
      specificity, and accuracy of the lever test were 83%, 80%, and 82%, respectively.
      Accuracy was not statistically different from the Lachman, AD, and pivot shift
      tests (P = .78, .99, .07, respectively). Subanalyses were performed based on the
      presence of another ligament tear, timing of injury, and the presence of a
      meniscus tear. Although the groups were smaller and thus underpowered, the
      results were reported. Neither the presence of another ligament tear nor the
      timing of the injury affected accuracy (P = .62 and P = .47); however, the
      presence of a meniscus tear decreased its accuracy (P = .003). CONCLUSIONS: The
      lever test showed high sensitivity, specificity, and overall accuracy in the
      detection of ACL tears. The accuracy of the lever test was not significantly
      different from the Lachman, AD, or pivot shift tests. LEVEL OF EVIDENCE: Level
      II, prospective comparative study.

PMID- 28499924
TI  - Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for
      Cardiovascular Disease.
AB  - Hypercholesterolemia is a well-known risk factor for a wide range of diseases in
      developed countries. Here, we report that mice lacking functional LDLR (low
      density lipoprotein receptor), an animal model of human familial
      hypercholesterolemia, show circadian abnormalities. In free running behavioral
      experiments in constant darkness, these mice showed a prolonged active phase and
      distinctly bimodal rhythms. Even when the circadian rhythms were entrained by
      light and dark cycles, these mice showed a significant attenuation of behavioral
      onset intensity at the start of the dark period. Further, we hypothesized that
      the combination of hypercholesterolemia and circadian abnormalities may affect
      cardiovascular disease progression. To examine this possibility, we generated
      LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing
      a mutation into Period2, a core clock gene, and found that these mice showed a
      significant enlargement of artery plaque area with an increase in inflammatory
      cytokine IL-6 levels. These results suggest that circadian dysfunction may be
      associated with the development or progression of cardiovascular diseases.

PMID- 28499925
TI  - Does Kruppel Like Factor 15 Play an Important Role in the Left Ventricular
      Hypertrophy of Patients with Type 2 Diabetes?

PMID- 28499926
TI  - Epigenetic Studies of Perinatal Determinants of Later Obesity Link Important, but
      Previously Unrelated, Genetic and Epidemiological Findings.

PMID- 28499923
TI  - The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior.
AB  - Despite being overexpressed in different tumor entities, RIO kinases are hardly
      characterized in mammalian cells. We investigated the role of these atypical
      kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer
      cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3,
      strongly impairs proliferation and invasiveness in conventional and 3D culture
      systems. Interestingly, these effects were mainly observed in RAS mutant cancer
      cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells
      is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1
      in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1
      activates NF-kappaB signaling and promotes cell cycle progression. Using
      proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to
      be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung
      colonization in vivo and that RIOK1 is overexpressed in different subtypes of
      human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential
      therapeutic target, especially in RAS-driven cancers.

PMID- 28499928
TI  - Detection of Ostreid herpesvirus-1 microvariants in healthy Crassostrea gigas
      following disease events and their possible role as reservoirs of infection.
AB  - Ostreid herpesvirus-1 microvariants (OsHV-1) cause severe mortalities in farmed
      Crassostrea gigas in Europe, New Zealand and Australia. Outbreaks are seasonal,
      recurring in the warmer months of the year in endemic estuaries. The reference
      genotype and microvariant genotypes of OsHV-1 have been previously detected in
      the tissues of apparently healthy adult oysters naturally exposed to OsHV-1 in
      the field. However, the role of such oysters as reservoirs of infection for
      subsequent mortality outbreaks remains unclear. The aims of this study were: (1)
      to identify the optimal sample type to use for the detection of OsHV-1 DNA in
      apparently healthy C. gigas; and (2) to assess whether live C. gigas maintained
      on-farm after an OsHV-1 related mortality event remain infected and could act as
      a reservoir host for subsequent outbreaks. OsHV-1 DNA was detected in the
      hemolymph, gill, mantle, adductor muscle, gonad and digestive gland of apparently
      healthy adult oysters. The likelihood of detecting OsHV-1 DNA in hemolymph was
      equivalent to that in gill and mantle, but the odds of detecting OsHV-1 DNA in
      hemolymph and gill were more than 8 times that of adductor muscle. Gill had the
      highest viral loads. Compared to testing whole gill homogenates, testing snippets
      of the gill improved the detection of OsHV-1 DNA by about four fold. The
      prevalence of OsHV-1 in gill and mantle was highest after the first season of
      OsHV-1 exposure; it then declined to low or negligible levels in the same cohorts
      in subsequent seasons, despite repeated seasonal exposure in monitoring lasting
      up to 4years. The hemolymph of individually identified oysters was repeatedly
      sampled over 15months, and OsHV-1 prevalence declined over that time frame in the
      youngest cohort, which had been exposed to OsHV-1 for the first time at the start
      of that season. In contrast, the prevalence in two cohorts of older oysters,
      which had been exposed to OsHV-1 in prior seasons, was consistently low (<10%).
      Viral loads were <104 DNA copies per mg tissue or MUL hemolymph, suggesting that
      OsHV-1 was not being maintained at or amplified to high quantities. Therefore,
      while OsHV-1 may persist within apparently healthy oysters that have survived an
      outbreak of disease, they may not be a major reservoir host for the virus for
      subsequent outbreaks. However, further investigation is required to ascertain
      whether OsHV-1 replication occurs in surviving oysters, and whether transmission
      from them to naive oysters and induction of clinical disease is possible.

PMID- 28499927
TI  - Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron
      Overload and Restrictive Lung Disease.
AB  - Emerging evidence suggests that pulmonary iron accumulation is implicated in a
      spectrum of chronic lung diseases. However, the mechanism(s) involved in
      pulmonary iron deposition and its role in the in vivo pathogenesis of lung
      diseases remains unknown. Here we show that a point mutation in the murine
      ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S),
      increases iron levels in alveolar macrophages, epithelial cells lining the
      conducting airways and lung parenchyma, and in vascular smooth muscle cells.
      Pulmonary iron overload is associated with oxidative stress, restrictive lung
      disease with decreased total lung capacity and reduced blood oxygen saturation in
      homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings
      implicate iron in lung pathology, which is so far not considered a classical iron
      related disorder.

PMID- 28499929
TI  - Reproductive efficiency of entomopathogenic nematodes as scavengers. Are they
      able to fight for insect's cadavers?
AB  - Entomopathogenic nematodes (EPNs) and their bacterial partners are well-studied
      insect pathogens, and their persistence in soils is one of the key parameters for
      successful use as biological control agents in agroecosystems. Free-living
      bacteriophagous nematodes (FLBNs) in the genus Oscheius, often found in soils,
      can interfere in EPN reproduction when exposed to live insect larvae. Both groups
      of nematodes can act as facultative scavengers as a survival strategy. Our
      hypothesis was that EPNs will reproduce in insect cadavers under FLBN presence,
      but their reproductive capacity will be severely limited when competing with
      other scavengers for the same niche. We explored the outcome of EPN - Oscheius
      interaction by using freeze-killed larvae of Galleria mellonella. The
      differential reproduction ability of two EPN species (Steinernema kraussei and
      Heterorhabditis megidis), single applied or combined with two FLBNs (Oscheius
      onirici or Oscheius tipulae), was evaluated under two different infective
      juvenile (IJ) pressure: low (3IJs/host) and high (20IJs/host). EPNs were able to
      reproduce in insect cadavers even in the presence of potential scavenger
      competitors, although EPN progeny was lower than that recorded in live larvae.
      Hence, when a highly susceptible host is available, exploiting cadavers by EPN
      might limit the adaptive advantage conferred by the bacteria partner, and might
      result in an important trade-off on long-term persistence. Contrary to our
      hypothesis, for most of the combinations, there were not evidences of competitive
      relationship between both groups of nematodes in freeze-killed larvae, probably
      because their interactions are subject to interference by the microbial growth
      inside the dead host. Indeed, evidences of possible beneficial effect of FLBN
      presence were observed in certain EPN-FLBN treatments compared with single EPN
      exposure, highlighting the species-specific and context dependency of these
      multitrophic interactions occurring in the soil.

PMID- 28499930
TI  - Working memory and attentional bias on reinforcing efficacy of food.
AB  - Reinforcing efficacy of food, or the relationship between food prices and
      purchasing, is related to obesity status and energy intake in adults. Determining
      how to allocate resources for food is a decision making process influenced by
      executive functions. Attention to appetitive cues, as well as working memory
      capacity, or the ability to flexibly control attention while mentally retaining
      information, may be important executive functions involved in food purchasing
      decisions. In two studies, we examined how attention bias to food and working
      memory capacity are related to reinforcing efficacy of both high energy-dense and
      low energy-dense foods. The first study examined 48 women of varying body mass
      index (BMI) and found that the relationship between attentional processes and
      reinforcing efficacy was moderated by working memory capacity. Those who avoid
      food cues and had high working memory capacity had the lowest reinforcing
      efficacy, as compared to those with low working memory capacity. Study 2
      systematically replicated the methods of study 1 with assessment of maintained
      attention in a sample of 48 overweight/obese adults. Results showed the
      relationship between maintained attention to food cues and reinforcing efficacy
      was moderated by working memory capacity. Those with a maintained attention to
      food and high working memory capacity had higher reinforcing efficacy than low
      working memory capacity individuals. These studies suggest working memory
      capacity moderated the relationship between different aspects of attention and
      food reinforcement. Understanding how decision making process are involved in
      reinforcing efficacy may help to identify future intervention targets.

PMID- 28499931
TI  - Empowered to cook: The crucial role of 'food agency' in making meals.
AB  - What makes an individual, on any given occasion, able and willing to prepare a
      meal for themselves: that is, to cook? As home cooking has increasingly become
      the focus of public-health, nutrition, and policy interventions and campaigns,
      the need for a better understanding has become apparent. It is clear that cooking
      is not merely a matter of mechanical skill or rote training; beyond this, it is
      difficult to explain why similar individuals have such different capacities for
      setting and achieving food-related goals. This paper proposes a new paradigm for
      cooking and food provisioning - termed "food agency" - that attempts to describe
      how an individual's desires form and are enacted in correspondence with social
      environments: broadly, agency emerges from the complex interplay of individual
      technical skills and cognitive capacities with social and cultural supports and
      barriers. Drawing on a close reading of anthropological and sociological research
      into cooking, the authors propose that an individual's ability to integrate such
      complexity in regard to provisioning - to possess 'food agency' - is crucial.
      This argument is supplemented by empirical case studies from a large body of
      ethnographic observations and interviews with home cooks from the United States,
      conducted over the last decade. Overall, more food agency means the cook is more
      empowered to act. Adopting the paradigm of food agency into the consideration of
      everyday cooking practices has the potential to support transdisciplinary food
      scholarship integrating individual actions within a food system and thus inform
      nutrition and public health interventions related to meal preparation.

PMID- 28499932
TI  - Dietary customs and food availability shape the preferences for basic tastes: A
      cross-cultural study among Polish, Tsimane' and Hadza societies.
AB  - Biological significance of food components suggests that preferences for basic
      tastes should be similar across cultures. On the other hand, cultural factors
      play an important role in diet and can consequently influence individual
      preference for food. To date, very few studies have compared basic tastes
      preferences among populations of very diverse environmental and cultural
      conditions, and research rather did not involve traditional populations for whom
      the biological significance of different food components might be the most
      pronounced. Hence, our study focused on basic taste preferences in three
      populations, covering a broad difference in diet due to environmental and
      cultural conditions, market availability, dietary habits and food acquirement: 1)
      a modern society (Poles, n = 200), 2) forager-horticulturalists from
      Amazon/Bolivia (Tsimane', n = 138), and 3) hunter-gatherers from Tanzania (Hadza,
      n = 85). The preferences for basic tastes were measured with sprays containing
      supra-threshold levels of sweet, sour, bitter, salty, and umami taste solutions.
      We observed several interesting differences between participating societies. We
      found that Tsimane' and Polish participants liked the sweet taste more than other
      tastes, while Hadza participants liked salty and sour tastes more than the
      remaining tastes. Further, Polish people found bitter taste particularly
      aversive, which was not observed in the traditional societies. Interestingly, no
      cross-cultural differences were observed for relative liking of umami taste - it
      was rated closely to neutral by members of all participating societies.
      Additionally, Hadza showed a pattern to like basic tastes that are more common to
      their current diet than societies with access to different food sources. These
      findings demonstrate the impact of diet and market availability on preference for
      basic tastes.

PMID- 28499934
TI  - Matrine promotes oligodendrocyte development in CNS autoimmunity through the
      PI3K/Akt signaling pathway.
AB  - AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix
      Sophorae flavescens, has been recently found to be beneficial in experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly
      through its anti-inflammatory effect. In the present study, we tested the effect
      of MAT on ongoing EAE and defined possible mechanisms underlying its effects on
      myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice
      and MAT treatment was started at disease onset. Clinical scores were monitored
      daily; spinal cords and the corpus callosum brain region of mice were harvested
      on day 23 p.i. for inflammatory infiltration and demyelination of the central
      nervous system. Myelin content and the development of oligodendrocytes and their
      precursors were determined by immunostaining, and expression of p-Akt, p-mTOR, p
      PI3K, and p-P70S6 was determined by Western blot. KEY FINDINGS: MAT effectively
      suppressed EAE severity and increased the expression of proteolipid protein, a
      myelin protein that is a marker of CNS myelin. MAT treatment largely increased
      the number of mature oligodendrocytes, and significantly activated the
      PI3K/Akt/mTOR signaling pathway, which is required for oligodendrocyte survival
      and axon myelination. SIGNIFICANCE: These findings demonstrate a beneficial
      effect of MAT on oligodendrocyte differentiation and myelination during EAE, most
      likely through activating the PI3K/Akt/mTOR signaling pathway.

PMID- 28499935
TI  - Sub-chronic lead exposure produces beta1-adrenoceptor downregulation decreasing
      arterial pressure reactivity in rats.
AB  - : Lead is considered a causative factor for hypertension and other cardiovascular
      diseases. AIMS: To investigate the effects of sub-chronic lead exposure on blood
      pressure reactivity and cardiac beta1-adrenoceptor activity and to evaluate
      whether the effects found in vitro are similar to those found in vivo. MAIN
      METHODS: Male Wistar rats were randomly distributed into two groups: control rats
      (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days.
      KEY FINDINGS: Blood pressure in the Pb rats increased starting from the first
      week of treatment until the end of the study [systolic blood pressure, Ct: 122+/
      4 vs. Pb: 143+/-3mmHg; diastolic blood pressure, Ct: 63+/-4 vs. Pb: 84+/-4mmHg].
      The heart rate was also increased (Ct: 299+/-11 vs. Pb: 365+/-11bpm), but the
      pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium
      exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats.
      Isoproterenol increased the left ventricular systolic and end-diastolic pressure,
      and heart rate only in Ct rats, suggesting that lead induced beta1-adrenoceptor
      downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb
      rats, suggesting the involvement of cyclooxygenase-derived products (which are
      associated with reduced nitric oxide bioavailability) in this process.
      SIGNIFICANCE: These findings offer further evidence that the effects of sub
      chronic lead exposure in vitro can be reproduced in vivo-even at low
      concentrations-thus triggering mechanisms for the development of hypertension.
      Therefore, lead should be considered an environmental risk factor for
      cardiovascular disease.

PMID- 28499936
TI  - Umbilical Cord Blood Transplantation without Antithymocyte Globulin Results in
      Similar Survival but Better Quality of Life Compared with Unrelated Peripheral
      Blood Stem Cell Transplantation for the Treatment of Acute Leukemia-A
      Retrospective Study in China.
AB  - Although previous studies have demonstrated improved outcomes in umbilical cord
      blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the
      conditioning regimen, this approach has not been comparatively studied in
      unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the
      risks and benefits between UCBT without ATG and UPBSCT in patients with acute
      leukemia (AL), we conducted a multicenter retrospective study of 79 patients who
      underwent UCBT (myeloablative conditioning without ATG) and 96 patients who
      underwent UPBSCT (myeloablative conditioning with ATG). The outcomes were graft
      failure, neutrophil engraftment, platelet engraftment, acute graft-versus-host
      disease (aGVHD), chronic graft-versus-host disease (cGVHD), transplantation
      related mortality (TRM), relapse, overall survival (OS), and leukemia-free
      survival (LFS). Follow-up was censored on October 31, 2016. Engraftment was
      similar between the 2 groups but granulocyte and platelet recovery were slower in
      the UCBT group (both P < .001). The incidences of aGVHD, TRM, OS, and LFS were
      similar between the 2 groups (all P > .05). Without ATG, the UCBT group displayed
      less cGVHD and less moderate and severe cGVHD (P < .001 and P = .004). The
      incidences of Epstein-Barr virus viremia and post-transplantation
      lymphoproliferative disease were significantly lower in the UCBT group (P < .001
      and P = .037). UCBT recipients had higher activity Karnofsky performance scores
      and 3-year GVHD-free/relapse-free survival than the UPBSCT group (P = .03 and P =
      .04). We observed similar survival when comparing UCBT without ATG and UPBSCT,
      but we also observed better quality of life in patients undergoing UCBT without
      ATG. We can therefore conclude that patients with primary AL for whom an
      appropriate HLA-matched sibling donor is not available could select either UCBT
      or UPBSCT.

PMID- 28499937
TI  - Haploidentical Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma
      Using Post-Transplantation Cyclophosphamide Graft-versus-Host Disease
      Prophylaxis.
AB  - Allogeneic (allo) hematopoietic cell transplantation (HCT) currently represents
      the only potentially curative therapy for patients affected by multiple myeloma
      (MM). Up to 30% of patients in western countries do not have a matched donor.
      Haploidentical HCT (haplo-HCT) may be an option, but currently, there are little
      available data regarding this treatment. We analyzed survival outcomes of 30
      heavily pretreated MM patients who received haplo-HCT with post-transplantation
      cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. Median
      neutrophil and platelet engraftments at day +30 were 87% (95% confidence interval
      [CI], 66% to 95%) and 60% (95% CI, 40% to 75%), respectively. The cumulative
      incidences of relapse or progression of disease (PD) and nonrelapse mortality at
      18 months were 42% (95% CI, 23% to 59%) and 10% (95% CI, 2% to 24%),
      respectively. The cumulative incidence of grade II to IV acute GVHD at day +100
      was 29% (95% CI, 14% to 47%). The cumulative incidence of chronic GVHD at 18
      months was 7% (95% CI, 1% to 21%). With a median follow-up in survivors of 25
      months (range, 15 to 73 months), the 18-month progression-free survival (PFS) and
      overall survival (OS) were 33% (95% CI, 17% to 50%) and 63% (95% CI, 44% to 78%),
      respectively. No differences were observed between peripheral blood and bone
      marrow graft in terms of engraftment, GVHD, or PD incidence. Chemorefractory
      disease at transplantation was associated with a lower/reduced 18-month PFS (9%
      versus 47%, P = .01) and OS (45% versus 74%, P = .03). This was explained by a
      higher PD incidence (55% versus 33%, P = .05). In this multicenter study, we
      report encouraging results with haplo-HCT for patients with heavily pretreated
      MM.

PMID- 28499938
TI  - Allogeneic Stem Cell Transplantation in Myelofibrosis.
AB  - Myeloproliferative neoplasm (MPN) is a category in the World Health Organization
      classification of myeloid tumors. BCR-ABL1-negative MPN is a subcategory that
      includes primary myelofibrosis (MF), post-essential thrombocythemia MF, and post
      polycythemia vera MF. These disorders are characterized by stem cell-derived
      clonal myeloproliferation. Clinically, these diseases present with anemia and
      splenomegaly and significant constitutional symptoms such as severe fatigue,
      symptoms associated with an enlarged spleen and liver, pruritus, fevers, night
      sweats, and bone pain. Multiple treatment options may provide symptom relief and
      improved survival; however, allogeneic stem cell transplantation (HCT) remains
      the only potentially curative option. The decision for a transplant is based on
      patient prognosis, age, comorbidities, and functional status. This review
      describes the recent data on various peritransplantation factors and their effect
      on outcomes of patients with MF and new therapeutic areas, such as the use and
      timing of Janus kinase inhibitors with HCT and gives overall conclusions from the
      available data in the published literature.

PMID- 28499939
TI  - Respecting death at the coal face.

PMID- 28499940
TI  - Effects of cardiopulmonary resuscitation time on chest wall compliance in
      patients with cardiac arrest.

PMID- 28499933
TI  - Major review: Molecular genetics of primary open-angle glaucoma.
AB  - Glaucoma is a leading cause of irreversible blindness worldwide. Primary open
      angle glaucoma (POAG), the most common type, is a complex inherited disorder that
      is characterized by progressive retinal ganglion cell death, optic nerve head
      excavation, and visual field loss. The discovery of a large, and growing, number
      of genetic and chromosomal loci has been shown to contribute to POAG risk, which
      carry implications for disease pathogenesis. Differential gene expression
      analyses in glaucoma-affected tissues as well as animal models of POAG are
      enhancing our mechanistic understanding in this common, blinding disorder. In
      this review we summarize recent developments in POAG genetics and molecular
      genetics research.

PMID- 28499941
TI  - MTUS1, a gene encoding angiotensin-II type 2 (AT2) receptor-interacting proteins,
      in health and disease, with special emphasis on its role in carcinogenesis.
AB  - Loss of tumor suppressor activity is a frequent event in the formation and
      progression of tumors and has been listed as an important hallmark of cancers.
      Microtubule-Associated Scaffold Protein 1 (MTUS1) is a candidate tumor suppressor
      gene which is reported to be frequently down-regulated in a variety of human
      cancers including pancreas, colon, bladder, head-and-neck, ovarian, breast
      cancers, gastric, lung cancers. It is also reported to be implicated in several
      types of pathologies such as cardiac hypertrophy, atherosclerosis, and SLE-like
      lymphoproliferative diseases. Moreover, MTUS1-encoded proteins are shown to be
      involved in the regulation of vital cellular processes such as proliferation,
      differentiation, DNA repair, inflammation, vascular remodeling and senescence.
      However, the current knowledge is very limited about the role of this gene in
      human cancers as well as other type diseases. Besides, there is no literature
      report which summarizes and criticizes the importance of MTUS1 in the cellular
      processes, especially in the processes of carcinogenesis. Accordingly, in this
      comprehensive review, we tried to shed light on the role of tumor suppressor
      MTUS1/ATIP in health and disease, putting special emphasis on its role in the
      development and progression of human cancers as well as associated molecular
      mechanisms and the reasons behind MTUS1/ATIP deficiency, which have been not well
      documented previously.

PMID- 28499942
TI  - Metformin ameliorates hypoxia/reoxygenation-induced cardiomyocyte apoptosis based
      on the SIRT3 signaling pathway.
AB  - Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death
      and disability worldwide. However, a limited number of therapies are available to
      minimize the detrimental effects of this injury. Recently, researchers have
      demonstrated that metformin exerts direct cardioprotective effects against H/R.
      The aim of this study was to investigate the underlying mechanisms of how
      metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study,
      the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as
      well as the levels of malondialdehyde (MDA) were measured. Following H/R injury,
      LDH activity and MDA levels were evidently increased, while SOD activity and cell
      viability significantly decreased. Surprisingly, metformin downregulated the
      levels of relative reactive oxygen species (ROS) and upregulated the levels of
      relative SOD following H/R injury. Furthermore, metformin-treated cells exhibited
      reduced cell death, which was demonstrated to be associated with increased SIRT3
      expression compared to that in the control group, as evidenced by blocking of the
      protective effects of metformin on cell apoptosis by the SIRT3 inhibitor
      Nicotinamide (NAM). Therefore, our results demonstrate that metformin improves
      cells viability following H/R, and this cardioprotective effect is partly
      mediated by the SIRT3 signaling pathway.

PMID- 28499943
TI  - Molecular cloning, transcriptional profiling, and subcellular localization of
      signal transducer and activator of transcription 2 (STAT2) ortholog from rock
      bream, Oplegnathus fasciatus.
AB  - Signal transducer and activator of transcription 2 (STAT2) is a key element that
      transduces signals from the cell membrane to the nucleus via the type I
      interferon-signaling pathway. Although the structural and functional aspects of
      STAT proteins are well studied in mammals, information on teleostean STATs is
      very limited. In this study, a STAT paralog, which is highly homologous to the
      STAT2 members, was identified from a commercially important fish species called
      rock bream and designated as RbSTAT2. The RbSTAT2 gene was characterized at
      complementary DNA (cDNA) and genomic sequence levels, and was found to possess
      structural features common with its mammalian counterparts. The complete cDNA
      sequence was distributed into 24 exons in the genomic sequence. The promoter
      proximal region was analyzed and found to contain potential transcription factor
      binding sites to regulate the transcription of RbSTAT2. Phylogenetic studies and
      comparative genomic structure organization revealed the distinguishable evolution
      for fish and other vertebrate STAT2 orthologs. Transcriptional quantification was
      performed by SYBR Green quantitative real-time PCR (qPCR) and the ubiquitous
      expression of RbSTAT2 transcripts was observed in all tissues analyzed from
      healthy fish, with a remarkably high expression in blood cells. Significantly
      (P<0.05) altered transcription of RbSTAT2 was detected after immune challenge
      experiments with viral (rock bream irido virus; RBIV), bacterial (Edwardsiella
      tarda and Streptococcus iniae), and immune stimulants (poly I:C and LPS).
      Antiviral potential was further confirmed by WST-1 assay, by measuring the
      viability of rock bream heart cells treated with RBIV. In addition, results of an
      in vitro challenge experiment signified the influence of rock bream interleukin
      10 (RbIL-10) on transcription of RbSTAT2. Subcellular localization studies by
      transfection of pEGFP-N1/RbSTAT2 into rock bream heart cells revealed that the
      RbSTAT2 was usually located in the cytoplasm and translocated near to the nucleus
      upon poly I:C administration. Altogether, these findings suggest that RbSTAT2 is
      involved in various biologically crucial mechanisms, and provides immune
      protection to the rock bream.

PMID- 28499944
TI  - Comparison of different coating techniques on the properties of FucoPol films.
AB  - Plasma deposition, liquid flame spray (LFS) and atomic layer deposition (ALD)
      were used to form inorganic coatings in new exopolysaccharide (FucoPol)
      biodegradable films. Coated films were characterised in terms of surface, optical
      and barrier properties in order to evaluate their potential use in food
      packaging. FucoPol films presented dense and homogeneous surface with instant
      water contact angle of 95. Plasma deposition of perfluorohexane (PFH) on FucoPol
      surface has not shown significant improvement in the hydrophobic behaviour over
      the time. The FucoPol coating of SiO2 nanoparticles deposited by LFS and plasma
      deposition of PFH have shown higher instant water contact angle (135 degrees )
      caused by coating surface roughness, but this hydrophobic behaviour was not
      stable over time. FucoPol films coated only with TiO2 deposited by ALD and
      combination of that with plasma deposition of PFH have shown stable water contact
      angle during time (90 and 115, respectively), transparency in the same order of
      magnitude and significantly lower permeability to water vapour (3.45*10-11mol/m s
      Pa and 3.45*10-11mol/m s Pa when compared to uncoated films with 5.32*10-11mol/m
      s Pa). Moreover, films coated with TiO2-PFH have also shown a permeability to
      oxygen of 1.70*10-16molm/m2sPa which is 67% lower than uncoated films.

PMID- 28499945
TI  - DSC investigation of bovine hide collagen at varying degrees of crosslinking and
      humidities.
AB  - Bovine hide collagen (nonCLC; non-CrossLinked Collagen) was analysed by
      differential scanning calorimetry (DSC) at different hydration degrees and
      compared with hide collagen samples crosslinked with glutaraldehyde (CLC-GA) and
      chromium(III) ions (CLC-Cr), respectively. Crosslinking and drying were confirmed
      to increase the denaturation temperature. Different regions were assigned, that
      reflect the variation of the influence of water on the denaturation temperature.
      Furthermore, at moderate hydration degrees, the enthalpies of non-crosslinked
      collagen increase compared to the fully hydrated state. This reflects a glue-like
      action of water in the range of 25% hydration. Crosslinking of bovine hide
      collagen decreases the enthalpy by 25% in the fully hydrated state, even at very
      low levels of crosslinking This can be explained by intensive effects of the
      crosslinking agent on the hydration network of the collagen molecules, assuming
      that the enthalpies are principally a result of hydrogen bonding. At very low
      water contents DSC peaks of CLC-Cr completely disappear. This could be explained
      by competition between hydroxosulfochromate(III) complexes and collagen for
      water.

PMID- 28499946
TI  - Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral
      delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and
      in vivo assessment.
AB  - The present work was to develop lipid drug conjugated (LDC) nanoparticles for the
      potential oral delivery of pemetrexed diacid (PTX) and evaluation of its in
      vitro, ex vivo and in vivo potentials. The LDC was prepared by salt formation of
      PTX with stearic acid and followed by cold homogenization technique to produce
      the LDC nanoparticles. FTIR analysis of LDC proved the presence of amide bond in
      LDC powder indicating the conjugation between drug and lipid. LDC nanoparticles
      was found to have particle size 121.9+/-1.85nm and zeta potential -51.6mV+/-1.23
      and entrapment efficiency 81.0+/-0.89%. TEM images revealed spherical morphology
      and were in corroboration with particle size measurements. Ex vivo gut permeation
      studies revealed a very good enhancement in permeation of drug present in the LDC
      as compared to plain drug solution and were confirmed by CLSM. MTT assay
      conformed significant% toxicity at the end of 24h and 48h. Furthermore, the AUC0
      24 of PTX from the optimized LDC nanoparticels was found to be 4.22 folds higher
      than that from PTX suspension on oral administration. Thus, LDC has high
      potential for the oral delivery of PTX in cancer therapy and future prospects for
      the industrial purpose.

PMID- 28499947
TI  - Effect of chemical denaturants on the conformational stability of GyrB subunit of
      DNA gyrase from Salmonella enterica serovar Typhi.
AB  - DNA gyrase, a type II topoisomerase maintains the topology of DNA by introducing
      negative supercoils using energy generated by ATP hydrolysis. It is composed of
      two subunits, GyrA and GyrB (GyrA2GyrB2 hetero-tetramer). GyrB comprises two
      domains, a 43kDa amino N-terminus (GBNTD) and 47kDa carboxyl C- terminus (GBCTD).
      Till now no study has been reported in terms of stability of Gyrase B and its
      domains using chemical denaturants related to its function. To understand the
      role of each domain in GyrB subunit, we estimated the thermodynamic stability of
      GBF and its individual domains using urea and GdmCl. Changes in secondary and
      tertiary structures were monitored using circular dichroism and fluorescence
      spectroscopy. The Cm values for GBNTD, GBCTD and GBF proteins were found to be
      2.25, 1.65 and 1.82M during GdmCl-induced denaturation and 2.95, 2.25 and 2.67M
      for urea-induced denaturation. It is observed that GBNTD is more stable than
      GBCTD and it contributes to overall stability of GyrB. The lower Cm and DeltaG
      values reflect the flexibility of GBCTD to form the catalytic site along with
      GANTD for cleavage or religation reaction. Both GdmCl- and urea-induced
      denaturation of GyrB domains were reversible over the entire range of
      concentration.

PMID- 28499948
TI  - Antibacterial and wound healing properties of chitosan/poly(vinyl alcohol)/zinc
      oxide beads (CS/PVA/ZnO).
AB  - Treatment against bacterial infection is crucial for wound healing. Development
      of cost-effective antibacterial agent with wound healing properties is still in
      high demand. In this study we aimed to design chitosan/poly(vinyl alcohol)/zinc
      oxide (CS/PVA/ZnO) beads as novel antibacterial agent with wound healing
      properties. CS/PVA/ZnO beads were synthesized, and characterized by using XRD,
      FTIR, SEM, and TEM analysis. Pure chitosan exhibits two peaks at 2theta=10 and 20
      and the CS/PVA polymer matrix exhibit the peaks at 2theta=19.7 degrees  and
      another of low intensity at 2theta=11.5 degrees . Pure ZnO shows the
      characteristic peaks at (100), (002), (101), (102), (110), (103), (200), and
      (112) that were in good agreement with wurtzite ore having hexagonal lattice
      structure. The antibacterial activity of CS/PVA/ZnO against Escherichia coli, and
      Staphylococcus aureus were evaluated with the zone of inhibition method.
      Antibacterial activity of CS/PVA/ZnO was higher than that of chitosan (CS) and
      poly(vinyl alcohol (PVA). Hemocompatibility and biocompatibility of CS/PVA/ZnO
      were tested in in vitro. Wound healing properties of CS/PVA/ZnO were tested in
      mice skin wound. CS/PVA/ZnO showed strong antimicrobial, wound healing effect,
      hemocompatibility and biocompatibility. Hence the results strongly support the
      possibility of using this novel CS/PVA/ZnO material for the anti bacterial and
      wound healing application.

PMID- 28499949
TI  - Optimization of polysaccharides extraction from Dictyophora indusiata and
      determination of its antioxidant activity.
AB  - Response surface methodology (RSM) was used to optimize the extraction conditions
      of polysaccharides from the fruiting body of Dictyophora indusiata (DIP). Effect
      of extraction time, extraction temperature and solid to liquid ratio on the yield
      of DIP was investigated. The optimum extraction conditions for DIP were as
      follows: extraction time, 2.1h, solid to liquid ratio, 1:37, and extraction
      temperature, 92 degrees C. Under these conditions, the experimental extraction
      yield of DIP was 15.95+/-0.144%, which was matched closely to the predicted
      value. During the antioxidant experiments in vitro, DIP exhibited a strong
      reducing capacity and strong scavenging activity on DPPH, superoxide, and
      hydroxyl radicals. The EC50 of DIP on DPPH, hydroxyl and superoxide radicals was
      0.89mg/L, 0.51mg/mL and 0.68mg/mL, respectively. This suggests that
      polysaccharides from D. indusiata have the potential to be the resources of
      natural antioxidants.

PMID- 28499950
TI  - Modifiable risk factors promoting neurodegeneration is associated with two novel
      brain degradation markers measured in serum.
AB  - There has been limited success with blood-based biomarkers of neurodegeneration.
      One perceived reason is that blood has no direct contact to the brain. Recently
      developed blood-based biomarkers of tau-degradation have shown promise as
      potential tools for peripheral assessment of neurodegeneration; however, factors
      contributing to the levels of these in blood are poorly understood. Using
      multiple linear regression analysis in cross-sectional data from an observational
      cohort (n = 5626), the aim was to examine which factors correlate to the
      serological levels of two novel biomarkers measuring truncated tau fragments (Tau
      A and Tau-C) in serum. Platelets, albumin and several modifiable risk factors,
      including Body Mass Index, high density lipoprotein and white blood cell count
      were associated with the serum level of tau fragments. The factors associated
      with tau in serum may promote neurodegeneration and alter the permeability of the
      Blood Brain Barrier through chronic inflammation and vascular dysfunction. These
      data are of key importance for understanding the mechanism of release and
      subsequent peripheral processing of tau from the brain and will assist in the
      development of future blood-based biomarkers.

PMID- 28499951
TI  - Effects of task-specific rehabilitation training on tau modification in rat with
      photothrombotic cortical ischemic damage.
AB  - Although stroke elicits progressive cognitive decline and is a leading cause of
      dementia, molecular interplay between stroke and Alzheimer's disease (AD)
      pathology has not been fully elucidated. Furthermore, studies on the effects of
      post-stroke rehabilitation on AD pathology are limited. We evaluated the acute
      effect of stroke on tau modification, and the molecular effects of task-specific
      training (TST) on tau modification using a model of photochemically-induced
      thrombosis (PIT)-induced cortical infarction. Following PIT in the dominant side
      of sensorimotor cortex, the rehabilitation group received 4-weeks of TST
      rehabilitation once daily by single pellet reaching training, whereas the
      sedentary control group did not received any type of training. Cortical
      expression levels of proteins related to tau modification were evaluated on post
      stroke day 1 (PSD1) and 28; functional tests were also evaluated performed every
      week. The expression levels of acetyl-tau, phosphorylated-tau (p-tau),
      cyclooxygenase-2 and Akt-mTORC1-p70S6K pathway in infarcted cortices on PSD1 were
      significantly greater, whereas the expression levels of p-AMPK were significantly
      lower than in the paired contralateral sides. TST rehabilitation for 4 weeks
      greatly improved functional motor performance but not memory, which concurred
      with the down-regulations of ipsilateral p-AMPK, cyclooxygenase-2, Akt-mTORC1
      p70S6K pathway, and p-tau in rehabilitation group. PIT-induced cortical
      infarction was found to induce cortical tau modification through the Akt-mTORC1
      p70S6K activation, and to suppress the expression of AMPK-related proteins. TST
      rehabilitation greatly improved motor function, but not memory, and suppressed p
      tau expression and neuroinflammation. Nevertheless, the role of TST-mediated
      regulation of tau hyperphosphorylation required further clarification.

PMID- 28499952
TI  - Data management plans: the missing perspective.
AB  - The National Institutes of Health requires data sharing plans for projects with
      over five hundred thousand dollars in direct costs in a single year and has
      recently released a new guidance on rigor and reproducibility in grant
      applications. The National Science Foundation outright requires Data Management
      Plans (DMPs) as part of applications for funding. However, there is no general
      and definitive list of topics that should be covered in a DMP for a research
      project. We identified and reviewed DMP requirements from research funders. Forty
      three DMP topics were identified. The review uncovered inconsistent requirements
      for written DMPs as well as high variability in required or suggested DMP topics
      among funder requirements. DMP requirements were found to emphasize post
      publication data sharing rather than upstream activities that impact data
      quality, provide traceability or support reproducibility. With the emphasis
      equalized, the forty-three identified topics can aid Data Managers in
      systematically generating comprehensive DMPs that support research project
      planning and funding application evaluation as well as data management conduct
      and post-publication data sharing.

PMID- 28499953
TI  - Analysis and modelling of septic shock microarray data using Singular Value
      Decomposition.
AB  - Being a high throughput technique, enormous amounts of microarray data has been
      generated and there arises a need for more efficient techniques of analysis, in
      terms of speed and accuracy. Finding the differentially expressed genes based on
      just fold change and p-value might not extract all the vital biological signals
      that occur at a lower gene expression level. Besides this, numerous mathematical
      models have been generated to predict the clinical outcome from microarray data,
      while very few, if not none, aim at predicting the vital genes that are important
      in a disease progression. Such models help a basic researcher narrow down and
      concentrate on a promising set of genes which leads to the discovery of gene
      based therapies. In this article, as a first objective, we have used the lesser
      known and used Singular Value Decomposition (SVD) technique to build a microarray
      data analysis tool that works with gene expression patterns and intrinsic
      structure of the data in an unsupervised manner. We have re-analysed a microarray
      data over the clinical course of Septic shock from Cazalis et al. (2014) and have
      shown that our proposed analysis provides additional information compared to the
      conventional method. As a second objective, we developed a novel mathematical
      model that predicts a set of vital genes in the disease progression that works by
      generating samples in the continuum between health and disease, using a simple
      normal-distribution-based random number generator. We also verify that most of
      the predicted genes are indeed related to septic shock.

PMID- 28499954
TI  - Systematic review and meta-analysis of gait mechanics in young and older adults.
AB  - BACKGROUND: Age-related gait changes may play a critical role in functional
      limitations of older adults. Despite sizable interest in determining how age
      alters walking mechanics, small sample sizes and varied outcome measures have
      precluded a comprehensive understanding of the impact of age on lower extremity
      joint kinematics and kinetics. OBJECTIVE: The aim of this study was to perform a
      systematic review and meta-analysis of the aging gait mechanics literature.
      METHODS: The overall standardized effect of age on walking mechanics was computed
      for 29 studies (200 standardized effects). To account for variation in reported
      outcome variables, analyses were carried out for comparisons between young and
      older adult results using all discrete kinematic or kinetic variables reported
      for the ankle, knee, or hip. Different variables reported for a given joint were
      then analyzed as separate categorical moderators. RESULTS: The overall
      standardized effect of age was large for ground reaction forces, moderate for
      ankle and small for knee and hip kinematics and ankle and hip kinetics. When the
      analysis was restricted to studies with similar or matched walking speed, the
      standardized effects of age remained similar except for hip power generation and
      knee kinematic variables. CONCLUSIONS: The results of this meta-analysis provide
      evidence to support moderate standardized effects, with and without consideration
      of walking speeds, for changes in lower extremity kinematics, joint moments and
      powers at the ankle, and ground reaction forces. The standardized effects of age
      for knee mechanics are less conclusive and would benefit from further research.

PMID- 28499955
TI  - Transcriptomic analysis of Saccharomyces cerevisiae upon honokiol treatment.
AB  - Honokiol (HNK), one of the main medicinal components in Magnolia officinalis,
      possesses antimicrobial activity against a variety of pathogenic bacteria and
      fungi. However, little is known of the molecular mechanisms underpinning the
      antimicrobial activity. To explore the molecular mechanism of its antifungal
      activity, we determined the effects of HNK on the mRNA expression profile of
      Saccharomyces cerevisiae using a DNA microarray approach. HNK markedly induced
      the expression of genes related to iron uptake and homeostasis. Conversely, genes
      associated with respiratory electron transport were downregulated, mirroring the
      effects of iron starvation. Meanwhile, HNK-induced growth deficiency was partly
      rescued by iron supplementation and HNK reacted with iron, producing iron
      complexes that depleted iron. These results suggest that HNK treatment induced
      iron starvation. Additionally, HNK treatment resulted in the upregulation of
      genes involved in protein synthesis and drug resistance networks. Furthermore,
      the deletion of PDR5, a gene encoding the plasma membrane ATP binding cassette
      (ABC) transporter, conferred sensitivity to HNK. Overexpression of PDR5 enhanced
      resistance of WT and pdr5Delta strains to HNK. Taken together, these findings
      suggest that HNK, which can be excluded by overexpression of Pdr5, functions in
      multiple cellular processes in S. cerevisiae, particularly in inducing iron
      starvation to inhibit cell growth.

PMID- 28499956
TI  - Group X hybrid histidine kinase Chk1 is dispensable for stress adaptation, host
      pathogen interactions and virulence in the opportunistic yeast Candida
      guilliermondii.
AB  - Hybrid histidine kinases (HHKs) progressively emerge as prominent sensing
      proteins in the fungal kingdom and as ideal targets for future therapeutics. The
      group X HHK is of major interest, since it was demonstrated to play an important
      role in stress adaptation, host-pathogen interactions and virulence in some yeast
      and mold models, and particularly Chk1, that corresponds to the sole group X HHK
      in Candida albicans. In the present work, we investigated the role of Chk1 in the
      low-virulence species Candida guilliermondii, in order to gain insight into
      putative conservation of the role of group X HHK in opportunistic yeasts. We
      demonstrated that disruption of the corresponding gene CHK1 does not influence
      growth, stress tolerance, drug susceptibility, protein glycosylation or cell wall
      composition in C. guilliermondii. In addition, we showed that loss of CHK1 does
      not affect C. guilliermondii ability to interact with macrophages and to
      stimulate cytokine production by human peripheral blood mononuclear cells.
      Finally, the C. guilliermondii chk1 null mutant was found to be as virulent as
      the wild-type strain in the experimental model Galleria mellonella. Taken
      together, our results demonstrate that group X HHK function is not conserved in
      Candida species.

PMID- 28499957
TI  - Costs of outpatient parenteral antimicrobial therapy (OPAT) administered by
      Hospital at Home units in Spain.
AB  - The aim of this study was to assess the direct healthcare costs of outpatient
      parenteral antimicrobial therapy (OPAT) administered by Hospital at Home (HaH)
      units in Spain. An observational, multicentre, economic evaluation of
      retrospective cohorts was conducted. Patients were treated at home by the HaH
      units of three Spanish hospitals between January 2012 and December 2013. From the
      cost accounting of HaH OPAT (staff, pharmacy, transportation, diagnostic tests
      and structural), the cost of each outpatient course was obtained following a top
      down strategy based on the use of resources. Costs associated with inpatient
      stay, if any, were estimated based on length of stay and ICD-9-CM diagnosis.
      There were 1324 HaH episodes in 1190 patients (median age 70 years). The median
      (interquartile range) stay at home was 10 days (7-15 days). Of the OPAT episodes,
      91.5% resulted in cure or improvement on completion of intravenous therapy. The
      mean total cost of each infectious episode was ?6707 [95% confidence interval
      (CI) ?6189-7406]. The mean cost per OPAT episode was ?1356 (95% CI ?1247-1560),
      mainly distributed between healthcare staff costs (46%) and pharmacy costs (39%).
      The mean cost of inpatient hospitalisation of an infectious episode was ?4357
      (95% CI ?3947-4977). The cost per day of inpatient hospitalisation was ?519,
      whilst the cost per day of OPAT was ?98, meaning a saving of 81%. This study
      shows that OPAT administered by HaH units resulted in lower costs compared with
      inpatient care in Spain.

PMID- 28499958
TI  - Unexpected persistence of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with
      imipenem.
AB  - Imipenem is active against extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E) but favours the intestinal emergence of resistance.
      The effects of imipenem on intestinal microbiota have been studied using culture
      based techniques. In this study, the effects were investigated in patients using
      culture and metagenomic techniques. Seventeen hospitalised adults receiving
      imipenem were included in a multicentre study (NCT01703299,
      http://www.clinicaltrials.gov). Most patients had a history of antibiotic use
      and/or hospitalisation. Stools were collected before, during and after imipenem
      treatment. Bacterial and fungal colonisation was assessed by culture, and
      microbiota changes were assessed using metagenomics. Unexpectedly, high
      colonisation rates by imipenem-susceptible ESBL-E before treatment (70.6%)
      remained stable over time, suggesting that imipenem intestinal concentrations
      were very low. Carriage rates of carbapenem-resistant Gram-negative bacilli (0
      25.0%) were also stable over time, whereas those of yeasts (64.7% before
      treatment) peaked at 76.5% during treatment and decreased thereafter. However,
      these trends were not statistically significant. Yeasts included highly diverse
      colonising Candida spp. Metagenomics showed no global effect of imipenem on the
      bacterial taxonomic profiles at the sequencing depth used but demonstrated
      specific changes in the microbiota not detected with culture, attributed to
      factors other than imipenem, including sampling site or treatment with other
      antibiotics. In conclusion, culture and metagenomics were highly complementary in
      characterising the faecal microbiota of patients. The changes observed during
      imipenem treatment were unexpectedly limited, possibly because the microbiota was
      already disturbed by previous antibiotic exposure or hospitalisation.

PMID- 28499959
TI  - Impact of initial empirical antifungal agents on the outcome of critically ill
      patients with invasive candidiasis: analysis of the China-SCAN study.
AB  - The effect of different empirical antifungal agents on the clinical outcome of
      critically ill patients with invasive candidiasis (IC) has not been fully
      elucidated. In this study, 136 patients with proven IC who received empirical
      therapy in the China-SCAN multicentre study were retrospectively analysed.
      Initial empirical antifungal monotherapy consisted of a triazole [fluconazole (n
      = 61), voriconazole (n = 20) or itraconazole (n = 12)] or an echinocandin (n =
      43). Hospital mortality as the primary outcome and global responses (clinical and
      microbiological) were assessed. The results indicated that rates of hospital
      mortality (P = 0.006) and intensive care unit (ICU) mortality (P = 0.011) were
      significantly lower in patients treated with an echinocandin compared with those
      receiving fluconazole, voriconazole or itraconazole. Multivariate regression
      analysis indicated that the type of antifungal agent used in empirical therapy
      was an independent predictor of hospital mortality (P = 0.033). Initial empirical
      echinocandin treatment was associated with decreased hospital mortality compared
      with fluconazole [odds ratio (OR) = 0.22, 95% confidence interval (CI) 0.06-0.85;
      P = 0.028], voriconazole (OR = 0.11, 95% CI 0.02-0.56; P = 0.008) or itraconazole
      (OR = 0.12, 95% CI 0.02-0.72; P = 0.020). Similar findings were observed for the
      clinical success endpoint. This study demonstrated that the initial empirical
      antifungal agent was an independent predictor of hospital mortality in critically
      ill patients with IC. Empirical therapy with an echinocandin was associated with
      decreased hospital mortality and greater clinical success than empirical therapy
      with fluconazole, voriconazole or itraconazole.

PMID- 28499960
TI  - Association between dipstick hematuria and decline in estimated glomerular
      filtration rate among Japanese patients with type 2 diabetes: A prospective
      cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 14)].
AB  - AIMS: To assess the association between dipstick hematuria and estimated
      glomerular filtration rate (eGFR) decline in Japanese patients with type 2
      diabetes. METHODS: Longitudinal data were obtained from 3068 Japanese patients
      with type 2 diabetes. To assess the independent association between dipstick
      hematuria and eGFR decline, we used Cox proportional hazard model adjusted for
      potential confounders. RESULTS: Median follow-up period was 699.7days. Mean age,
      body mass index (BMI), and HbA1c level were 65.7years, 24.6kg/m2, and 7.5%
      (58.1mmol/mol), respectively. Positive dipstick hematuria was significantly
      associated with baseline eGFR and severity of albuminuria (p<0.001). The
      multivariable-adjusted hazard ratio for eGFR decline in patients with dipstick
      hematuria compared with those without dipstick hematuria was 2.19 [95% confidence
      interval (CI): 1.22-3.91]; this association remained significant even after the
      exclusion of patients who did not have diabetic retinopathy (hazard ratio: 2.39;
      95% CI: 1.13-5.04). CONCLUSION: Positive dipstick hematuria was associated with
      severity of albuminuria and renal function. A significant association was found
      between dipstick hematuria and increased risk of eGFR decline among patients with
      type 2 diabetes. Therefore, our results suggest that dipstick hematuria is
      perhaps indicative of more severe diabetic nephropathy.

PMID- 28499961
TI  - Towards an improved global understanding of treatment and outcomes in people with
      type 2 diabetes: Rationale and methods of the DISCOVER observational study
      program.
AB  - AIM: Contemporary global real-world data on the management of type 2 diabetes are
      scarce. The global DISCOVER study program aims to describe the disease management
      patterns and a broad range of associated outcomes in patients with type 2
      diabetes initiating a second-line glucose-lowering therapy in routine clinical
      practice. METHODS: The DISCOVER program comprises two longitudinal observational
      studies involving more than 15,000 patients in 38 countries across six
      continents. Study sites have been selected to be representative of type 2
      diabetes management in each country. Data will be collected at baseline
      (initiation of second-line therapy), at 6months, and yearly during a 3-year
      follow-up period. RESULTS: The DISCOVER program will record patient, healthcare
      provider, and healthcare system characteristics, treatment patterns, and factors
      influencing changes in therapy. In addition, disease control (e.g. achievement of
      glycated hemoglobin target), management of associated risk factors (e.g.
      hypercholesterolemia and hypertension), and healthcare resource utilization will
      be recorded. Microvascular and macrovascular complications, incidence of
      hypoglycemic events, and patient-reported outcomes will also be captured.
      CONCLUSIONS: The DISCOVER program will provide insights into the current
      management of patients with type 2 diabetes worldwide, which will contribute to
      informing future clinical guidelines and improving patient care.

PMID- 28499962
TI  - Diabetes and male sex are key risk factor correlates of the extent of coronary
      artery calcification: A Euro-CCAD study.
AB  - BACKGROUND AND AIMS: Although much has been written about the conventional
      cardiovascular risk factor correlates of the extent of coronary artery
      calcification (CAC), few studies have been carried out on symptomatic patients.
      This paper assesses the potential ability of risk factors to associate with an
      increasing CAC score. METHODS: From the European Calcific Coronary Artery Disease
      (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients,
      62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had
      conventional cardiovascular risk factor assessment and CT scanning for CAC
      scoring. RESULTS: Among all patients, male sex (OR = 4.85, p<0.001) and diabetes
      (OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with
      age, hypertension, dyslipidemia and smoking also showing a relationship. Among
      patients with CAC, age, diabetes, hypertension and dyslipidemia were associated
      with an increasing CAC score in males and females, with diabetes being the
      strongest dichotomous risk factor (p<0.001 for both). These results were echoed
      in quantile regression, where diabetes was consistently the most important
      correlate with CAC extent in every quantile in both males and females. To a
      lesser extent, hypertension and dyslipidemia were also associated in the high CAC
      quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age
      and male sex in the total population, diabetes is the most important correlate of
      CAC extent in both sexes.

PMID- 28499963
TI  - Neither artificial light at night, anthropogenic noise nor distance from roads
      are associated with oxidative status of nestlings in an urban population of
      songbirds.
AB  - Increasing urbanization is responsible for road-related pollutants and causes an
      unprecedented increase in light and noise pollution, with potential detrimental
      effects for individual animals, communities and ecosystems. These stressors
      rarely act in isolation but studies dissecting the effects of these multiple
      stressors are lacking. Moreover, studies on urban stressors have mainly focused
      on adults, while exposure in early-life may be detrimental but is largely
      ignored. To fill this important knowledge gap, we studied if artificial light at
      night, anthropogenic noise and road-related pollution (using distance from roads
      as a proxy) explain variation in oxidative status in great tit nestlings (Parus
      major) in an urban population. Artificial light at night, anthropogenic noise and
      distance from roads were not associated with variation of the nine studied
      metrics of oxidative status (superoxide dismutase-SOD-, glutathione peroxidase
      GPX, catalase-CAT-, non-enzymatic total antioxidant capacity-TAC-, reduced
      glutathione-GSH-, oxidized glutathione-GSSG-, ratio GSH/GSSG, protein carbonyls
      and thiobarbituric acid reactive substances-TBARS). Interestingly, for all
      oxidative status metrics, we found that there was more variation in oxidative
      status among individuals of the same nest compared to between different nests. We
      also showed an increase in protein carbonyls and a decrease of the ratio GSH/GSSG
      as the day advanced, and an increase of GPX when weather conditions deteriorated.
      Our study suggests that anthropogenic noise, artificial light at night and road
      related pollution are not the most important sources of variation in oxidative
      status in great tit nestlings. It also highlights the importance of considering
      bleeding time and weather conditions in studies with free-living animals.

PMID- 28499964
TI  - Life-history dependent relationships between body condition and immunity, between
      immunity indices in male Eurasian tree sparrows.
AB  - In free-living animals, recent evidence indicates that innate, and acquired,
      immunity varies with annual variation in the demand for, and availability of,
      food resources. However, little is known about how animals adjust the
      relationships between immunity and body condition, and between innate and
      acquired immunity to optimize survival over winter and reproductive success
      during the breeding stage. Here, we measured indices of body condition (size
      corrected mass [SCM], and hematocrit [Hct]), constitutive innate immunity (plasma
      total complement hemolysis activity [CH50]) and acquired immunity (plasma
      immunoglobulin A [IgA]), plus heterophil/lymphocyte (H/L) ratios, in male
      Eurasian tree sparrows (Passer montanus) during the wintering and the breeding
      stages. We found that birds during the wintering stage had higher IgA levels than
      those from the breeding stage. Two indices of body condition were both negatively
      correlated with plasma CH50 activities, and positively with IgA levels in
      wintering birds, but this was not the case in the breeding birds. However, there
      was no correlation between CH50 activities and IgA levels in both stages. These
      results suggest that the relationships between body condition and immunity can
      vary across life-history stage, and there are no correlations between innate and
      acquired immunity independent of life-history stage, in male Eurasian tree
      sparrows. Therefore, body condition indices predict immunological state,
      especially during the non-breeding stage, which can be useful indicators of
      individual immunocompetences for understanding the variations in innate and
      acquired immunity in free-living animals.

PMID- 28499965
TI  - Effects of dietary dandelion extracts on growth performance, body composition,
      plasma biochemical parameters, immune responses and disease resistance of
      juvenile golden pompano Trachinotus ovatus.
AB  - The present study was conducted to investigate the effects of dietary dandelion
      extracts (DE) supplementation on growth performance, feed utilization, body
      composition, plasma biochemical indices, immune responses, hepatic antioxidant
      abilities, and resistance to the pathogen Vibrio harveyi in Trachinotus ovatus. A
      basal diet supplemented with DE at 0, 0.50, 1.00, 2.00, 4.00 and 10.00 g kg-1
      were fed to golden pompano for 8 weeks. The study indicated that dietary
      supplementation with DE could significantly improve final body weight (FBW),
      weight gain rate (WGR), specific growth rate (SGR), feed efficiency ratio (FER),
      feed intake (FI), protein efficiency ratio (PER) and protein deposit rate (PDR)
      (P < 0.05). The highest FBW, WGR, SGR, FI and PDR were observed in fish fed 1.00
      g kg-1 dietary DE (P < 0.05). The highest FER and PER were recorded at 0.50 g kg
      1 dietary DE (P < 0.05). Condition factor, viscerosomatic index, hepatosomatic
      index and survival were not significantly different among all groups. Fish fed
      1.00 g kg-1 dietary DE showed significant increase in plasma total protein,
      complement 4 content and alkaline phosphatase, lysozyme, glutathione reductase
      (GSR) activity, but significant decrease in triglyceride, low density lipoprotein
      cholesterol, malondialdehyde (MDA) content and aspartate aminotransferase
      activities compared to the control group (P < 0.05). Hepatic antioxidant enzymes
      (SOD, T-AOC, CAT, GSH-Px, GSR) significantly increased whereas MDA content
      significantly decreased in fish fed 1.00 g kg-1 DE supplement (P < 0.05). After
      challenge with Vibrio harveyi, significant higher post-challenge survival was
      observed in fish fed DE supplement (P < 0.05). These results indicated that
      golden pompano fed a diet supplemented with DE (especially at 1.00 g kg-1 of fed
      supplement) could significantly promote its growth performance, feed utilization,
      body protein deposit, immune ability, hepatic and plasma antioxidative enzyme
      activities and improve its resistance to infection by Vibrio harveyi.

PMID- 28499966
TI  - Interferon-induced protein 56 (IFI56) is induced by VHSV infection but not by
      bacterial infection in olive flounder (Paralichthys olivaceus).
AB  - Interferon-inducible protein 56 (IFI56, also known as ISG56/IFIT1, interferon
      induced protein with tetratricopeptide repeats 1) is strongly induced in response
      to interferon and a potent inhibitor of viral replication and translational
      initiation. Here, we describe the identification of IFI56 (OfIFI56) in olive
      flounder, its characteristic features, and expression levels in various tissues
      before and after viral hemorrhagic septicemia virus (VHSV) infection. The full
      length OfIFI56 sequence was identified from rapid amplification of cDNA ends PCR.
      The complete coding sequence of OfIFI56 is 1971 bp in length and encodes 431
      amino acids. The putative OfIFI56 protein has multiple tetratricopeptide (TPR)
      motifs, which regulate diverse biological processes, such as organelle targeting,
      protein import, and vesicle fusion. Based on sequence analysis, the Larimichthys
      crocea IFI56 protein (61%) had the highest sequence homology to OfIFI56. In
      healthy olive flounder, OfIFI56 mRNA expression was detected in many tissues such
      as intestine, gill, head kidney, heart, spleen, and trunk kidney tissues. After
      VHSV challenge, OfIFI56 mRNA was significantly up-regulated in these tissues.
      Additionally, OfIFI56 expression was induced by poly I:C but not by Streptococcus
      parauberis and S. iniae infection or lipopolysaccharide injection in kidney and
      spleen tissues of olive flounder. These results demonstrate that piscine OfIFI56
      expression is not induced by bacterial infection but is selectively induced by
      viral infection, especially VHSV, and that OfIFI56 may play an important role in
      the host response against VHSV infection.

PMID- 28499967
TI  - Molecular cloning, expression and antioxidative activity of 2-cys-peroxiredoxin
      from freshwater mussel Cristaria plicata.
AB  - Peroxiredoxins (Prxs) play an important role against various oxidative stresses
      by catalyzing the reduction of hydrogen peroxide (H2O2) and organic
      hydroperoxides to less harmful form. A 2-cys peroxiredoxin, designated as CpPrx,
      was cloned from hemocytes of freshwater mussel Cristaria plicata. The full length
      cDNA of CpPrx is 1247 bp, which includes an open reading frame (ORF) of 591bp,
      encoding 196 amino acids. CpPrx possesses two conserved cysteine residues (Cys49,
      Cys170). The deduced amino acid sequence of CpPrx showed a high level (67-74%) of
      sequence similarity to 2-Cys Prxs from other species. The results of real-time
      quantitative PCR revealed that CpPrx mRNA was constitutively expressed in
      tissues, and the highest expression levels were in hepatopancreas and gills.
      After peptidoglycan (PGN) and Aeromonas hydrophila challenge, the expression
      levels of CpPrx mRNA were up-regulated in hemocytes and hepatopancreas. The cDNA
      of CpPrx was cloned into the plasmid pET-32, and the recombinant protein was
      expressed in Escherichia coli BL21(DE3). Comparison with DE3-pET-32 and DE3
      strain, the cells of DE3-pET-32-CpPrx exhibited resistance to the concentration
      of 0.4, 0.8 and 1.2 mmoL/L H2O2 in vivo.

PMID- 28499968
TI  - Normal behavioral responses to light and darkness and the pupillary light reflex
      are dependent upon the olivary pretectal nucleus in the diurnal Nile grass rat.
AB  - The olivary pretectal nucleus (OPT) is a midbrain structure that receives
      reciprocal bilateral retinal projections, is involved in the pupillary light
      reflex, and connects reciprocally with the intergeniculate leaflet (IGL), a
      retinorecipient brain region that mediates behavioral responses to light pulses
      (i.e., masking) in diurnal Nile grass rats. Here, we lesioned the OPT and
      evaluated behavioral responses in grass rats to various lighting conditions, as
      well as their anxiety-like responses to light exposure. While control grass rats
      remained diurnal, grass rats with OPT lesions exhibited a more night-active
      pattern under 12h:12h light-dark (LD) conditions. However, when placed in
      constant darkness, OPT-lesioned grass rats became more active during their
      subjective day, suggesting that an exaggerated masking response to light may be
      responsible for the effect of OPT lesions on locomotor activity in LD. To test
      this hypothesis, we presented dark and light pulses to controls and grass rats
      with OPT lesions; controls increased their activity in response to light, whereas
      those with OPT lesions significantly increased activity in response to darkness.
      Further, when placed in a 7-h ultradian LD cycle, animals with OPT lesions were
      more active during darkness than controls. OPT lesions also abolished the
      pupillary light reflex, but did not affect anxiety-like behaviors. Finally, in
      animals with OPT lesions, light did not induce Fos expression in the
      ventrolateral geniculate nucleus, as it did in controls. Altogether, these
      results suggest that masking responses to light and darkness are dependent upon
      nuclei within the subcortical visual shell in grass rats.

PMID- 28499969
TI  - Corticotropin-releasing hormone modulates airway vagal preganglionic neurons of
      Sprague-Dawley rats at multiple synaptic sites via activation of its type 1
      receptors: Implications for stress-associated airway vagal excitation.
AB  - Corticotropin-releasing hormone release is the final common pathway of stress
      associated neuroendocrine responses. This study tested how corticotropin
      releasing hormone modulates airway vagal preganglionic neurons. Airway vagal
      preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent
      dye and identified in medullary slices, and their responses to corticotropin
      releasing hormone (200nmolL-1) were examined using whole-cell patch clamp. The
      results show that under current clamp, corticotropin-releasing hormone (200nmolL
      1) depolarized airway vagal preganglionic neurons and significantly increased the
      rate of their spontaneous firing. Under voltage clamp, corticotropin-releasing
      hormone caused a tonic inward current and significantly facilitated the
      spontaneous glutamatergic and GABAergic inputs of these neurons. Corticotropin
      releasing hormone had no impact on the spontaneous glycinergic inputs of these
      neurons. In the preexistence of tetrodotoxin (1MUmolL-1), corticotropin-releasing
      hormone had no impact on the miniature excitatory or inhibitory postsynaptic
      currents, but still induced a tonic inward current and significantly increased
      the input resistance. The responses induced by corticotropin-releasing hormone
      were prevented by Antalarmin hydrochloride (50MUmolL-1), an antagonist of type 1
      corticotropin-releasing hormone receptors, but insensitive to Astressin 2B
      (200nmolL-1), an antagonist of type 2 corticotropin-releasing hormone receptors.
      These results suggest that corticotropin-releasing hormone excites airway vagal
      preganglionic neurons via activation of its type 1 receptors at multiple sites,
      which includes a direct postsynaptic excitatory action and presynaptic
      facilitation of both glutamatergic and GABAergic inputs. In stress, corticotropin
      releasing hormone might be able to activate the airway vagal nerves and,
      consequently, participate in induction or exacerbation of airway disorders.

PMID- 28499970
TI  - Chitinase1 contributed to a potential protection via microglia polarization and
      Abeta oligomer reduction in D-galactose and aluminum-induced rat model with
      cognitive impairments.
AB  - Chitinase activity is increased in Alzheimer's disease (AD). However, the role of
      chitinase1 in AD is unknown. We investigated the effects of chitinase1 on
      Alzheimer's pathology and microglia function. Artificial chitinase1 and chitinase
      inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on
      inflammatory factors and beta-amyloid (Abeta) oligomers deposition in D
      galactose/AlCl3-induced rat model with cognitive impairments. Abeta-treated N9
      microglia cells were analyzed to further verify whether the changes in
      inflammatory factors following chitinase1 treatment were associated with
      microglia alternative activation. Our data displayed that the activity of
      chitinase1 was both improved in D-galactose/AlCl3-injected rats and Abeta
      pretreated microglia. Moreover, there was an improvement in cognitive function in
      chitinase1-treated AD rats. Furthermore, anti-inflammation factors (Arginase 1,
      Arg-1, mannose receptor type C 1, MRC1/CD206) were increased and pro-inflammation
      factors (tumor necrosis factor alpha, TNFalpha, interleukin 1 beta, IL-1beta)
      were decreased in D-galactose/AlCl3-induced AD rats with chitinase1 treatment. A
      higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1
      markers (TNFa, IL-1beta) were obtained in Abeta-pretreated N9 cells with
      chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2
      phenotype. We also detected that chitnase1 could weaken the deposition of Abeta
      oligomers in the brain of D-galactose/ AlCl3-induced AD rats. In conclusion,
      Chitinase1 might exert protective effects against AD by polarizing microglia to
      an M2 phenotype and resisting Abeta oligomer deposition.

PMID- 28499971
TI  - Selective reward affects the rate of saccade adaptation.
AB  - In this study we tested whether a selective reward could affect the adaptation of
      saccadic eye movements in monkeys. We induced the adaptation of saccades by
      displacing the target of a horizontal saccade vertically as the eye moved toward
      it, thereby creating an apparent vertical dysmetria. The repeated upward target
      displacement caused the originally horizontal saccade to gradually deviate upward
      over the course of several hundred trials. We induced this directional adaptation
      in both right- and leftward saccades in every experiment (n=20). In half of the
      experiments (n=10), we rewarded monkeys only when they made leftward saccades and
      in the other half (n=10) only for rightward saccades. The reaction time of
      saccades in the rewarded direction was shorter and we, like others, interpreted
      this change as a sign of the reward's preferential effect in that direction.
      Saccades in the rewarded direction showed more rapid adaptation of their
      directions than did saccades in the non-rewarded direction, indicating that the
      selective reward increased the speed of saccade adaptation. The differences in
      adaptation speed were reflected in changes in saccade metrics, which were usually
      more noticeable in the deceleration phases of saccades than in their acceleration
      phases. Because previous studies have shown that the oculomotor cerebellum is
      involved with saccade deceleration and also participates in saccade adaptation,
      it is possible that selective reward could influence cerebellar plasticity.

PMID- 28499972
TI  - Simvastatin ameliorates memory impairment and neurotoxicity in streptozotocin
      induced diabetic mice.
AB  - Diabetes comes with an additional burden of moderate to severe hyperlipidemia,
      but little is known about the effects of lipid-lowering therapy on diabetic
      complications such as diabetes-associated cognitive decline. Herein we
      investigated the effects of statins on memory impairment and neurotoxicity in
      streptozotocin-induced diabetic mice. Our data indicated that oral administration
      of simvastatin at 10 or 20mg/kg for 4weeks significantly ameliorated diabetes
      associated memory impairment reflected by performance better in the Morris water
      maze and Y-maze tests. The further study showed that these treatments caused
      significant increase of peroxisome proliferator-activated receptors gamma and
      decrease of NF-kappaB p65 in nucleus of hippocampus and cortex, and ameliorated
      neuroinflammatory response as evidenced by less Iba-1-positive cells and lower
      inflammatory mediators including IL-1beta, IL-6 and TNF-alpha as well as
      suppressed neuronal apoptosis as indicated by decreased TUNEL-positive cells,
      increased ratio of Bcl-2/Bax and decreased caspase-3 activity in the hippocampus
      and cortex. Moreover, simvastatin pronouncedly attenuated amyloidogenesis by
      decreasing amyloid-beta, amyloid precursor protein (APP) and beta-site APP
      cleaving enzyme-1. As expected, treated with simvastatin, the diabetic mice
      exhibited significant improvement of hyperlipidemia rather than hyperglycemia.
      Our findings disclosed novel therapeutic potential of simvastatin for the
      diabetes-associated cognitive impairment.

PMID- 28499973
TI  - Activation of dopamine D1 receptors enhances the temporal summation and
      excitability of rat retinal ganglion cells.
AB  - Dopamine (DA), an important neurotransmitter and neuromodulator, plays important
      roles in neuronal physiological functions by activating G-protein-coupled DA D1
      and/or D2 receptors. Previous studies have demonstrated that D1 receptors are
      functionally expressed in retinal neurons and glial cells, including ganglion
      cells. In this study, we explored the effects of D1 receptor activation on
      retinal ganglion cell (RGC) temporal summation and excitability in rat retinal
      slices using electrophysiological techniques. Bath application of the selective
      D1 receptor agonist SKF81297 increased the ratio of excitatory postsynaptic
      potentials (EPSPs) (EPSP5/EPSP1) within an EPSP train evoked by a train
      stimulation (five current pulses at 40Hz), which was blocked by co-application of
      SCH23390, a specific D1 receptor antagonist. Ba2+, an inwardly rectifying K+
      channel (Kir) blocker, significantly suppressed the SKF81297-induced effect,
      whereas ZD7288, a specific hyperpolarization-activated cation current (Ih)
      blocker, showed a moderate inhibitory effect. The cAMP/protein kinase A (PKA)
      signaling pathway, but not phosphoinositide-specific phospholipase C (PI-PLC),
      mediated the SKF81297-induced modulation of EPSP temporal summation. Further
      experiments showed that SKF81297 suppressed Ba2+-sensitive Kir currents in RGCs.
      Additionally, SKF81297 increased the spontaneous firing frequency of RGCs, and
      caused depolarization of the cells with or without the presence of synaptic
      receptor blockers. In contrast, SKF81297 did not significantly change the
      frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in
      RGCs. Our results indicate that D1 receptor activation enhances the temporal
      summation of RGCs mainly by suppressing Kir currents through the cAMP/PKA
      signaling pathway, thus increasing the excitability of rat RGCs.

PMID- 28499974
TI  - Prefrontal cortical glutathione-dependent defense and proinflammatory mediators
      in chronically isolated rats: Modulation by fluoxetine or clozapine.
AB  - Chronic psychosocial stress modulates brain antioxidant systems and causes
      neuroinflammation that plays a role in the pathophysiology of depression.
      Although the antidepressant fluoxetine (FLX) represents the first-line treatment
      for depression and the atypical antipsychotic clozapine (CLZ) is considered as a
      second-line treatment for psychotic disorders, the downstream mechanisms of
      action of these treatments, beyond serotonergic or dopaminergic signaling, remain
      elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and
      levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male
      Wistar rats exposed to 21days of chronic social isolation (CSIS). We also tested
      the ability of FLX (15mg/kg/day) or CLZ (20mg/kg/day), applied during CSIS, to
      prevent stress-induced changes. CSIS caused depressive- and anxiety-like
      behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B
      (NF-kappaB) activation with a concomitant increase in cytosolic levels of
      proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis
      factor-alpha in the PFC. NF-kappaB activation and proinflammatory response in the
      PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX
      preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS
      induced GSH depletion, but it diminished its levels when applied to non-stressed
      rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory
      response underlying depressive- and anxiety-like states induced by CSIS were
      prevented by FLX. The protective effect of CLZ, which was equally effective as
      FLX on the behavioral level, was limited to proinflammatory components. Hence,
      different mechanisms underlie the protective effects of these two drugs in CSIS
      rats.

PMID- 28499975
TI  - Intracortical signal processing of periodontal ligament sensations in rat.
AB  - The somatosensory information from the orofacial region, including the
      periodontal ligament (PDL), is processed in a manner that differs from that used
      for other body somatosensory information in the related cortices. It was reported
      that electrical stimulation to rat PDL elicited activation of the insular oral
      region (IOR) and the primary (S1) and secondary (S2) somatosensory cortices.
      However, the physiological relationship between S1 and S2/IOR is not well
      understood. To address this issue, we performed in vivo optical imaging using a
      voltage-sensitive dye. Our results demonstrated that the electrical stimulation
      to the PDL of the mandibular incisor evoked the simultaneous activation of S1 and
      the S2/IOR. The stimulation to the initial response area of the S1 evoked
      responses in the S2/IOR, and vice versa. An injection of tetrodotoxin (TTX) to
      the cortical region between S1 and S2/IOR attenuated such elicited responses only
      in the non-stimulated cortical partner site. The cortico-cortical interaction
      between S1 and S2/IOR was suppressed by the application of TTX, indicating that
      these two cortical regions bi-directionally communicate the signal processing of
      PDL sensations. An injection of FluoroGoldTM (FG) to the initial response area in
      S1 or the S2/IOR showed that FG-positive cells were scattered in the non-injected
      cortical counterpart. This morphological result demonstrated the presence of a bi
      directional intracortical connection between the initial response areas in S1 and
      the S2/IOR. These findings suggest the presence of a mutual connection between S1
      and the S2/IOR as an intracortical signal processing network for orofacial
      nociception.

PMID- 28499976
TI  - Daily modulation of the speed-accuracy trade-off.
AB  - Goal-oriented arm movements are characterized by a balance between speed and
      accuracy. The relation between speed and accuracy has been formalized by Fitts'
      law and predicts a linear increase in movement duration with task constraints. Up
      to now this relation has been investigated on a short-time scale only, that is
      during a single experimental session, although chronobiological studies report
      that the motor system is shaped by circadian rhythms. Here, we examine whether
      the speed-accuracy trade-off could vary during the day. Healthy adults carried
      out arm-pointing movements as accurately and fast as possible toward targets of
      different sizes at various hours of the day, and variations in Fitts' law
      parameters were scrutinized. To investigate whether the potential modulation of
      the speed-accuracy trade-off has peripheral and/or central origins, a motor
      imagery paradigm was used as well. Results indicated a daily (circadian-like)
      variation for the durations of both executed and mentally simulated movements, in
      strictly controlled accuracy conditions. While Fitts' law was held for the whole
      sessions of the day, the slope of the relation between movement duration and task
      difficulty expressed a clear modulation, with the lowest values in the afternoon.
      This variation of the speed-accuracy trade-off in executed and mental movements
      suggests that, beyond execution parameters, motor planning mechanisms are
      modulated during the day. Daily update of forward models is discussed as a
      potential mechanism.

PMID- 28499977
TI  - Human neural stem/progenitor cells derived from the olfactory epithelium express
      the TrkB receptor and migrate in response to BDNF.
AB  - Neurogenesis constitutively occurs in the olfactory epithelium of mammals,
      including humans. The fact that new neurons in the adult olfactory epithelium
      derive from resident neural stem/progenitor cells suggests a potential use for
      these cells in studies of neural diseases, as well as in neuronal cell
      replacement therapies. In this regard, some studies have proposed that the human
      olfactory epithelium is a source of neural stem/progenitor cells for autologous
      transplantation. Although these potential applications are interesting, it is
      important to understand the cell biology and/or whether human neural
      stem/progenitor cells in the olfactory epithelium sense external signals, such as
      brain-derived neurotrophic factor (BDNF), that is also found in other pro
      neurogenic microenvironments. BDNF plays a key role in several biological
      processes, including cell migration. Thus, we characterized human neural
      stem/progenitor cells derived from the olfactory epithelium (hNS/PCs-OE) and
      studied their in vitro migratory response to BDNF. In the present study, we
      determined that hNS/PCs-OE express the protein markers Nestin, Sox2, Ki67 and
      betaIII-tubulin. Moreover, the doubling time of hNS/PCs-OE was approximately 38h.
      Additionally, we found that hNS/PCs-OE express the BDNF receptor TrkB, and
      pharmacological approaches showed that the BDNF-induced (40ng/ml) migration of
      differentiated hNS/PCs-OE was affected by the compound K252a, which prevents TrkB
      activation. This observation was accompanied by changes in the number of vinculin
      adhesion contacts. Our results suggest that hNS/PCs-OE exhibit a migratory
      response to BDNF, accompanied by the turnover of adhesion contacts.

PMID- 28499978
TI  - Salt Taste Recognition in a Heart Failure Cohort.
AB  - BACKGROUND: Heart failure (HF) disproportionately affects older adults. Dietary
      sodium indiscretion is frequently implicated in HF decompensation. The affinity
      for and ability to taste salt in this process is unexplored. We sought to
      evaluate differences in salt taste by age and HF diagnosis and to map changes
      after hospitalization for acute decompensated heart failure (ADHF). METHODS:
      Seventy-two subjects underwent initial salt-taste testing during hospitalization
      for ADHF. Follow-up taste testing occurred at discharge and 1, 4, and 12 weeks
      after hospitalization. Three different groups were included as control subjects
      and underwent 1-time salt-taste testing: 10 patients with stable HF, 10 healthy
      older adults, and 10 healthy younger adults. Salt-taste testing was completed
      with the use of commercially available and validated Salsave test strips with
      increasing concentrations of NaCl (0.6-1.6 mg/cm2) to identify salt taste
      recognition threshold. Respectively, 2-sample t tests, multiple regression, and
      linear mixed-effects modeling were used for intergroup comparisons, to adjust for
      confounders, and to assess the effect of time after discharge from ADHF
      hospitalization. RESULTS: The baseline salt taste recognition threshold was
      lowest in the young healthy control group (0.62 [SD 0.05] mg/cm2 NaCl) compared
      with the healthy older control subjects (0.92 [SD 0.29] mg/cm2 NaCl), stable HF
      outpatients, (1.06 [SD 0.22] mg/cm2 NaCl), and ADHF subjects on admission (1.06
      [SD 0.48] mg/cm2 NaCl). There was a strong trend toward higher recognition
      threshold in HF patients (P = .051) that was independent from age and other
      potential confounders. Serial salt-taste testing in the ADHF group demonstrated a
      decrease in recognition threshold that persisted over the 12 weeks after
      discharge (1.04 [SD 0.44] to 0.76 [SD 0.22] mg/cm2 NaCl; P = .003). DISCUSSION:
      When compared with young healthy control subjects, HF patients have impaired
      recognition of salt taste. The salt taste recognition threshold decreases after
      hospitalization for ADHF. This change demonstrates the first evidence of the
      phenomenon known as the "hedonic shift" in HF, in which the threshold to
      recognize salt taste decreases after prescribed sodium restriction.

PMID- 28499979
TI  - Inspiratory Muscle Training Improves Intercostal and Forearm Muscle Oxygenation
      in Patients With Chronic Heart Failure: Evidence of the Origin of the Respiratory
      Metaboreflex.
AB  - BACKGROUND: The impact of inspiratory muscle training (IMT) on respiratory and
      peripheral muscle oxygenation and perfusion during inspiratory muscle fatigue in
      patients with chronic heart failure (HF) has not been established. METHODS AND
      RESULTS: Twenty-six patients with chronic HF were randomly assigned to either 8
      weeks of IMT or a control group. Inspiratory fatigue was induced by means of a
      progressive inspiratory resistive loading protocol until there was an inability
      to sustain inspiratory pressure, when the inspiratory muscle metaboreflex should
      be activated. The main outcomes were intercostal and forearm muscle oxygen
      saturation and deoxygenation as measured by means of near-infrared spectroscopy
      (NIRS) and blood lactate levels. Inspiratory muscle strength was increased by 78%
      (P <.001) after 8 weeks of participation in the IMT group. IMT attenuated the
      reduction of oxygen saturation in intercostal and forearm muscles and the
      increase in blood lactate during respiratory fatigue (P <.001 and P <.05,
      respectively). These changes were different from the control group (P <.01, P
      <.05, and P <.05, respectively). After 8 weeks, similar increases in oxygen
      consumption, mean arterial pressure, heart rate, stroke volume, and cardiac
      output were observed in both groups during respiratory fatigue. CONCLUSIONS: This
      randomized controlled clinical trial demonstrates that IMT attenuates the
      respiratory muscle oxygen demand-delivery mismatch during respiratory fatigue in
      patients with chronic HF.

PMID- 28499980
TI  - Morphological and molecular identification of Sarcocystis arctica sarcocysts in
      three red foxes (Vulpes vulpes) from the Czech Republic.
AB  - Muscular sarcocystosis by Sarcocystis arctica was found for the first time in the
      Czech Republic, in different muscles of red fox (Vulpes vulpes). Cysts were slim,
      elongated, thread-like, whitish, 1-7mm long, and 206-270MUm wide; bradyzoites
      were 7.9*2.7MUm in unstained wet mounts and 9.2*2.9MUm in cyst Giemsa-stained
      smears. The cyst wall was thin, with short villi-like protrusions, and no host
      response was observed in the histological sections. Examination of the
      distribution and intensity of sarcocysts in 17 different muscle groups revealed
      that the highest intensity was in the cranial tibial muscle (>15 cysts in
      compressoria), followed by the diaphragm, forearm, and other groups (with
      intensities of 3-15 cysts in compressoria). Sarcocysts were detected in 3 out of
      86 foxes. Genetic characterization at 18S rRNA, 28S rRNA, ITS1 and cox1,
      consistently showed that the species was identical with S. arctica.
      Interestingly, this protozoan was also detected as a co-infection in 3 foxes with
      the nematode Trichinella spp. for the first time.

PMID- 28499981
TI  - Mitochondrial dysfunction in ocular disease: Focus on glaucoma.
AB  - Mitochondrial dysfunction commonly presents with ocular findings as a part of a
      systemic disorder. These ophthalmic manifestations can be the first sign of a
      mitochondrial abnormality, which highlights the key role of a comprehensive
      ophthalmic assessment. On the other hand, a number of visually disabling genetic
      and acquired eye diseases with no curative treatment show abnormal mitochondrial
      function. Recent advances in mitochondrial research have improved our
      understanding of previously unexplained ocular disorders utilising better
      diagnostic approaches. Further studies on mitochondrial dysfunction and novel
      modalities of treatment will help to improve outcomes of these conditions. In
      this review article we discuss the clinical picture of common mitochondrial
      related eye diseases, diagnostic approaches and possible treatment options
      including a very recent interesting report about gene therapy, with a particular
      focus on glaucoma.

PMID- 28499982
TI  - Identification of FASTKD2 compound heterozygous mutations as the underlying cause
      of autosomal recessive MELAS-like syndrome.
AB  - Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS) is a condition that affects many parts of the body, particularly the
      brain and muscles. This study examined a Korean MELAS-like syndrome patient with
      seizure, stroke-like episode, and optic atrophy. Target sequencing of whole mtDNA
      and 73 nuclear genes identified compound heterozygous mutations p.R205X and
      p.L255P in the FASTKD2. Each of his unaffected parents has one of the two
      mutations, and both mutations were not found in 302 controls. FASTKD2 encodes a
      FAS-activated serine-threonine (FAST) kinase domain 2 which locates in the
      mitochondrial inner compartment. A FASTKD2 nonsense mutation was once reported as
      the cause of a recessive infantile mitochondrial encephalomyopathy. The present
      case showed relatively mild symptoms with a late onset age, compared to a
      previous patient with FASTKD2 mutation, implicating an inter-allelic clinical
      heterogeneity. Because this study is the second report of an autosomal recessive
      mitochondrial encephalomyopathy patient with a FASTKD2 mutation, it will extend
      the phenotypic spectrum of the FASTKD2 mutation.

PMID- 28499983
TI  - Photostimulation of mitochondria as a treatment for retinal neurodegeneration.
AB  - Absorption of photon energy by neuronal mitochondria leads to numerous downstream
      neuroprotective effects. Red and near infrared (NIR) light are associated with
      significantly less safety concerns than light of shorter wavelengths and they are
      therefore, the optimal choice for irradiating the retina. Potent neuroprotective
      effects have been demonstrated in various models of retinal damage, by red/NIR
      light, with limited data from human studies showing its ability to improve visual
      function. Improved neuronal mitochondrial function, increased blood flow to
      neural tissue, upregulation of cell survival mediators and restoration of normal
      microglial function have all been proposed as potential underlying mechanisms of
      red/NIR light.

PMID- 28499984
TI  - Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma
      and ocular hypertension: A case series.
AB  - Glaucoma is the most common optic neuropathy in humans and the leading cause of
      irreversible blindness worldwide. Its prevalence and incidence increase
      exponentially with ageing and raised intraocular pressure (IOP), while increasing
      evidence suggests that systemic mitochondrial abnormalities may also be
      implicated in its pathogenesis. We have recently shown that patients who have not
      developed glaucoma despite being exposed for many years to high IOP (ocular
      hypertension - OHT) have more efficient mitochondria, measured in peripheral
      blood lymphocytes, when compared to age-similar controls and fast progressing
      normal tension glaucoma (NTG) patients. In this prospective case series we aimed
      to explore some of the molecular pathways involved in mitochondrial efficiency in
      glaucoma resistance by measuring the systemic activity (in peripheral blood) of
      key mitochondrial regulators: the mammalian target of rapamycin (mTOR) and its
      major upstream regulators and downstream effectors that form the PTEN-Akt1-mTOR
      signalling pathway. We found no statistically significant difference in the
      systemic mTOR activity between the three groups (control, NTG and OHT). In line
      with the mTOR results, there was no significant difference in the activity of
      both the two major upstream mTOR regulators (PTEN and Akt1) and its two main
      downstream effectors (S6K and 4EBP1). In a single NTG patient, with history of
      Raynaud's, significantly higher mTOR activity was noted. We conclude that the
      PTEN-Akt1-mTOR pathway does not appear to play a central role in mitochondrial
      efficiency in OHT.

PMID- 28499985
TI  - Functional miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms and the
      susceptibility to hepatocellular carcinoma: An updated meta-analysis.
AB  - OBJECTIVE: Single nucleotide polymorphisms of miRNAs play important roles in the
      pathogenesis of hepatocellular carcinoma (HCC). To evaluate the association
      between four common miRNAs (miR-146a rs2910164; miR-149 rs2292832; miR-196a2
      rs11614913 and miR-499 rs3746444) and HCC risk, an updated meta-analysis was
      performed. METHODS: 32 studies including 12,405 HCC cases and 15,056 controls
      were used for this meta-analysis. There were 22 studies with 7894 cases and
      10,221 controls for miR-146a, 9 studies with 2684 HCC cases and 3464 controls for
      miR-149, 17 studies with 6937 cases and 8217 controls for miR-196a2 and 16
      studies with 4158 cases and 5264 controls for miR-499. Odds radios (ORs) and 95%
      confidence intervals (CIs) were used to assess the HCC risk. RESULTS: Meta
      analysis showed that miR-146a was associated with HCC risk under the heterozygote
      model (OR=1.10, 95%CI=1.03-1.17, P=0.007), whereas no association was found in
      Caucasian using all genetic models. For miR-196a2 polymorphism, an increased risk
      of HCC was observed based on four models (C vs T: OR=1.15, 95%CI=1.05-1.26,
      P=0.003; CC vs TT: OR=1.35, 95%CI=1.12-1.63, P=0.002; CC+CT vs TT: OR=1.20,
      95%CI=1.04-1.37, P=0.01 and CC vs CT+TT: OR=1.23, 95%CI=1.06-1.42, P=0.006).
      Association of miR-499 with HCC risk was only detected in the subgroup of studies
      which did not use polymerase chain reaction and restriction fragment length
      polymorphism (PCR-RFLP) under the allelic, heterozygote and dominant models.
      However, negative results were obtained for the association of miR-149 and HCC
      susceptibility. CONCLUSION: Our results suggest that miR-146a and miR-196a2
      polymorphisms are associated with increased risk of HCC, especially in Asian.

PMID- 28499986
TI  - N-acetylcysteine treatment attenuates the cognitive impairment and synaptic
      plasticity loss induced by streptozotocin.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder pathologically
      characterized by severe neuronal and glial structural changes and progressive
      cognitive decline. N-acetylcysteine (NAC) is a well-known pharmacological agent
      with pro-neurogenic properties and neuroprotective effects. In this study, we
      evaluated NAC protective effects on cognitive impairment and associated
      pathological markers in a streptozotocin (STZ)-induced sporadic dementia of AD
      type mice model. Animals were divided into six groups: I) Sham, II) NAC, III)
      physostigmine (PHY), IV) STZ, V) NAC + STZ and VI) PHY + NAC. NAC (5 mg/kg) and
      PHY (0.25 mg/kg) were administrated orally for 30 consecutive days and STZ (2.5
      mg/kg) intracerebroventricularly at the first and third days. Novel object
      recognition (NOR, days 26-27) and Morris water maze (MWM, days 26-30) tasks were
      assessed to evaluate learning and memory. On the thirty-first day animals were
      euthanized and brains collected for biochemical analysis. Interestingly, our
      results showed that STZ treatment induced cognitive impairment in mice in the NOR
      and MWM tasks. Both NAC and PHY treatments prevented from this impairment. The
      increase in AChE activity and decrease in pTrkB and MnSOD levels caused by STZ in
      the cerebral cortex and hippocampus, were prevented by the NAC and PHY
      treatments. The decrease in SYN, MAP2 and GFAP expressions were also prevented by
      NAC and PHY treatments. In conclusion, NAC treatment prevented the cognitive
      impairment induced by STZ, normalizing the AChE activity and rescuing the
      synaptic plasticity loss. Our results suggest that NAC is a promising therapeutic
      strategy for the treatment of AD.

PMID- 28499987
TI  - Evoked potentials in final epoch of self-initiated hand movement: A study in
      patients with depth electrodes.
AB  - Comparison between the intended and performed motor action can be expected to
      occur in the final epoch of a voluntary movement. In search for
      electrophysiological correlates of this mental process the purpose of the current
      study was to identify intracerebral sites activated in final epoch of self-paced
      voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42
      epileptic patients who performed self-paced voluntary movement task. Evoked
      potentials starting at 0 to 243ms after the peak of averaged, rectified
      electromyogram were identified in 21 regions of 13 subjects. The mean amplitude
      value of these late movement potentials (LMP) was 56.4+/-27.5MUV. LMPs were
      observed in remote regions of mesiotemporal structures, cingulate, frontal,
      temporal, parietal, and occipital cortices. Closely before the LMP onset, a
      significant increase of phase synchronization was observed in all EEG record
      pairs in 9 of 10 examined subjects; p<0.001, Mann-Whitney U test. In conclusion,
      mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital
      cortices seem to represent integral functionally linked parts of network
      activated in final epoch of self-paced voluntary movement. Activation of this
      large-scale neuronal network was suggested to reflect a comparison process
      between the intended and actually performed motor action. Our results contribute
      to better understanding of neural mechanisms underlying goal-directed behavior
      crucial for creation of agentive experience.

PMID- 28499989
TI  - Melanocortin Receptor Accessory Proteins (MRAPs): Functions in the melanocortin
      system and beyond.
AB  - G-protein coupled receptors (GPCRs) are regulated by numerous proteins including
      kinases, G-proteins, beta-arrestins and accessory proteins. Several families of
      GPCR accessory proteins like Receptor Activity Modifying Proteins, Receptor
      Transporting Proteins and Melanocortin Receptor Accessory Proteins (MRAPs) have
      been identified as regulator of receptor trafficking, signaling and ligand
      specificity. The MRAP family contains two members, MRAP1 and MRAP2, responsible
      for the formation of a functional ACTH receptor and for the regulation of energy
      homeostasis respectively. Like all known GPCR accessory proteins, MRAPs are
      single transmembrane proteins, however, they form a unique structure since they
      assemble as an anti-parallel homodimer. Moreover, the accepted idea that MRAPs
      are specific regulators of melanocortin receptors was recently challenged by the
      discovery that MRAP2 inhibits the activity of prokineticin receptors. Recent
      studies are starting to explain the role of the unusual structure of MRAPs and to
      illustrate the importance of MRAP2 for the maintenance of both energy and glucose
      homeostasis. This article is part of a Special Issue entitled: Melanocortin
      Receptors - edited by Ya-Xiong Tao.

PMID- 28499991
TI  - An Interactive Simulator for Imposing Virtual Musculoskeletal Dynamics.
AB  - OBJECTIVE: disease processes are often marked by both neural and muscular changes
      that alter movement control and execution, but these adaptations are difficult to
      tease apart because they occur simultaneously. This is addressed by swapping an
      individual's limb dynamics with a neurally controlled facsimile using an
      interactive musculoskeletal simulator (IMS) that allows controlled modifications
      of musculoskeletal dynamics. This paper details the design and operation of the
      IMS, quantifies and describes human adaptation to the IMS, and determines whether
      the IMS allows users to move naturally, a prerequisite for manipulation
      experiments. METHODS: healthy volunteers (n = 4) practiced a swift goal-directed
      task (back-and-forth elbow flexion/extension) for 90 trials with the IMS off
      (normal dynamics) and 240 trials with the IMS on, i.e., the actions of a user's
      personalized electromyography-driven musculoskeletal model are robotically
      imposed back onto the user. RESULTS: after practicing with the IMS on, subjects
      could complete the task with end-point errors of 1.56 degrees , close to the
      speed-matched IMS-off error of 0.57 degrees . Muscle activity, joint torque, and
      arm kinematics for IMS-on and -off conditions were well matched for three
      subjects (root-mean-squared error [RMSE] = 0.16 N.m), but the error was higher
      for one subject with a small stature (RMSE = 0.25 N.m). CONCLUSION: a well
      matched musculoskeletal model allowed IMS users to perform a goal-directed task
      nearly as well as when the IMS was not active. SIGNIFICANCE: this advancement
      permits real-time manipulations of musculoskeletal dynamics, which could increase
      our understanding of muscular and neural co-adaptations to injury, disease,
      disuse, and aging.

PMID- 28499992
TI  - Segmentation and Quantification for Angle-Closure Glaucoma Assessment in Anterior
      Segment OCT.
AB  - Angle-closure glaucoma is a major cause of irreversible visual impairment and can
      be identified by measuring the anterior chamber angle (ACA) of the eye. The ACA
      can be viewed clearly through anterior segment optical coherence tomography (AS
      OCT), but the imaging characteristics and the shapes and locations of major
      ocular structures can vary significantly among different AS-OCT modalities, thus
      complicating image analysis. To address this problem, we propose a data-driven
      approach for automatic AS-OCT structure segmentation, measurement, and screening.
      Our technique first estimates initial markers in the eye through label transfer
      from a hand-labeled exemplar data set, whose images are collected over different
      patients and AS-OCT modalities. These initial markers are then refined by using a
      graph-based smoothing method that is guided by AS-OCT structural information.
      These markers facilitate segmentation of major clinical structures, which are
      used to recover standard clinical parameters. These parameters can be used not
      only to support clinicians in making anatomical assessments, but also to serve as
      features for detecting anterior angle closure in automatic glaucoma screening
      algorithms. Experiments on Visante AS-OCT and Cirrus high-definition-OCT data
      sets demonstrate the effectiveness of our approach.

PMID- 28499990
TI  - A State Space and Density Estimation Framework for Sleep Staging in Obstructive
      Sleep Apnea.
AB  - OBJECTIVE: Although the importance of sleep is increasingly recognized, the lack
      of robust and efficient algorithms hinders scalable sleep assessment in healthy
      persons and those with sleep disorders. Polysomnography (PSG) and visual/manual
      scoring remain the gold standard in sleep evaluation, but more
      efficient/automated systems are needed. Most previous works have demonstrated
      algorithms in high agreement with the gold standard in healthy/normal (HN)
      individuals-not those with sleep disorders. METHODS: This paper presents a
      statistical framework that automatically estimates whole-night sleep architecture
      in patients with obstructive sleep apnea (OSA)-the most common sleep disorder.
      Single-channel frontal electroencephalography was extracted from 65 HN/OSA sleep
      studies, and decomposed into 11 spectral features in 60 903 30 s sleep epochs.
      The algorithm leveraged kernel density estimation to generate stage-specific
      likelihoods, and a 5-state hidden Markov model to estimate per-night sleep
      architecture. RESULTS: Comparisons to full PSG expert scoring revealed the
      algorithm was in fair agreement with the gold standard (median Cohen's kappa =
      0.53). Further, analysis revealed modest decreases in median scoring agreement as
      OSA severity increased from HN (kappa = 0.63) to severe (kappa = 0.47). A
      separate implementation on HN data from the Physionet Sleep-EDF Database resulted
      in a median kappa = 0.65, further indicating the algorithm's broad applicability.
      CONCLUSION: Results of this work indicate the proposed single-channel framework
      can emulate expert-level scoring of sleep architecture in OSA. SIGNIFICANCE:
      Algorithms constructed to more accurately model physiological variability during
      sleep may help advance automated sleep assessment, for practical and general use
      in sleep medicine.

PMID- 28499993
TI  - Robust 2-D-3-D Registration Optimization for Motion Compensation During 3-D TRUS
      Guided Biopsy Using Learned Prostate Motion Data.
AB  - In magnetic resonance (MR)-targeted, 3-D transrectal ultrasound (TRUS)-guided
      biopsy, prostate motion during the procedure increases the needle targeting error
      and limits the ability to accurately sample MR-suspicious tumor volumes. The
      robustness of the 2-D-3-D registration methods for prostate motion compensation
      is impacted by local optima in the search space. In this paper, we analyzed the
      prostate motion characteristics and investigated methods to incorporate such
      knowledge into the registration optimization framework to improve robustness
      against local optima. Rigid motion of the prostate was analyzed adopting a
      mixture-of-Gaussian (MoG) model using 3-D TRUS images acquired at bilateral
      sextant probe positions with a mechanically assisted biopsy system. The learned
      motion characteristics were incorporated into Powell's direction set method by
      devising multiple initial search positions and initial search directions.
      Experiments were performed on data sets acquired during clinical biopsy
      procedures, and registration error was evaluated using target registration error
      (TRE) and converged image similarity metric values after optimization. After
      incorporating the learned initialization positions and directions in Powell's
      method, 2-D-3-D registration to compensate for motion during prostate biopsy was
      performed with rms +/- std TRE of 2.33 +/- 1.09 mm with ~3 s mean execution time
      per registration. This was an improvement over 3.12 +/- 1.70 mm observed in
      Powell's standard approach. For the data acquired under clinical protocols, the
      converged image similarity metric value improved in >=8% of the registrations
      whereas it degraded only <=1% of the registrations. The reported improvements in
      optimization indicate useful advancements in robustness to ensure smooth clinical
      integration of a registration solution for motion compensation that facilitates
      accurate sampling of the smallest clinically significant tumors.

PMID- 28499994
TI  - Observation of Nonlinear Harmonic Generation of Bulk Modes in SAW Devices.
AB  - Nonlinear generation of harmonics is measured on the wafer level on temperature
      compensated surface-acoustic-wave resonators on lithium niobate. The second
      harmonic response features strong peaks looking like multiple resonant modes. The
      product of the frequency difference between the successive peaks to the substrate
      thickness is found to remain almost constant. The results also show that the
      level of the harmonic signal strongly depends on the roughness of the back side
      of the substrate. Due to these findings, it was assumed that the signal is due to
      nonlinear generation of a bulk mode. This assumption is confirmed experimentally
      by measuring the second-harmonic wave field on the back side of the substrate
      with an interferometer. Possible nonlinear mechanisms explaining these results
      are discussed.

PMID- 28499995
TI  - Large-Scale Nonlinear Lumped and Integrated Field Simulations of Top-Orthogonal
      to-Bottom-Electrode CMUT Architectures.
AB  - Capacitive micromachined ultrasonic transducers (CMUTs) promise many advantages
      over traditional piezoelectric transducers such as the potential to construct
      large, cost-effective 2-D arrays. To avoid wiring congestion issues associated
      with fully wired arrays, top-orthogonal-to-bottom electrode (TOBE) CMUT array
      architectures have proven to be a more practical alternative, using only 2N wires
      for an N *N array. Optimally designing a TOBE CMUT array is a significant
      challenge due to the range of parameters from the device level up to the
      operating conditions of the entire array. Since testing many design variations
      can be prohibitively expensive, a simulation approach accounting for both the
      small and large-scale array characteristics of TOBE arrays is essential. In this
      paper, we demonstrate large-scale TOBE CMUT array simulations using a nonlinear
      CMUT lumped-circuit model. We investigate the performance of the array with
      different CMUT design parameters and array operating conditions. These simulated
      results are then compared with measurements of TOBE arrays fabricated using a
      sacrificial release process.

PMID- 28499996
TI  - Modeling and Analysis of Lateral Propagation of Surface Acoustic Waves Including
      Coupling Between Different Waves.
AB  - This paper discusses lateral propagation of surface acoustic waves (SAWs) in
      periodic grating structures when two types of SAWs exist simultaneously and are
      coupled. The thin plate model proposed by the authors is extended to include the
      coupling between two different SAW modes. First, lateral SAW propagation in an
      infinitely long periodic grating is modeled and discussed. Then, the model is
      applied to the Al-grating/42 degrees  YX-LiTaO3 (42-LT) substrate structure, and
      it is shown that the slowness curve shape changes from concave to convex with the
      Al grating thickness. The transverse responses are also analyzed on an infinitely
      long interdigital transducer on the structure, and good agreement is achieved
      between the present and the finite-element method analyses. Finally, SAW
      resonators are fabricated on the Cu grating/42-LT substrate structure, and it is
      experimentally verified that the slowness curve shape of the shear horizontal SAW
      changes with the Cu thickness.

PMID- 28499988
TI  - Melanocortin neurons: Multiple routes to regulation of metabolism.
AB  - The burden of disability, premature death, escalating health care costs and lost
      economic productivity due to obesity and its associated complications including
      hypertension, stroke, cardiovascular disease and type 2 diabetes is staggering
      [1,2]. A better understanding of metabolic homeostatic pathways will provide us
      with insights into the biological mechanisms of obesity and how to fundamentally
      address this epidemic [3-6]. In mammals, energy balance is maintained via a
      homeostatic system involving both peripheral and central melanocortin systems;
      changes in body weight reflect an unbalance of the energetic state [7-9].
      Although the primary cause of obesity is unknown, there is significant effort to
      understand the role of the central melanocortin pathway in the brain as it has
      been shown that deficiency of proopiomelanocortin (POMC) [10,11] and melanocortin
      4 receptors (MC4R) [12-15] in both rodents and humans results in severe
      hyperphagia and obesity [16-23]. In this review, we will summarize how the
      central melanocortin pathway helps regulate body mass and adiposity within a
      'healthy' range through the 'nutrient sensing' network [24-28]. This article is
      part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong
      Tao.

PMID- 28499997
TI  - Enhancement of Visual Comfort and Sense of Presence on Stereoscopic 3D Images.
AB  - Conventional stereoscopic 3D (S3D) displays do not provide accommodation depth
      cues of the 3D image or video contents being viewed. The sense of content depths
      is thus limited to cues supplied by motion parallax (for 3D video), stereoscopic
      vergence cues created by presenting left and right views to the respective eyes,
      and other contextual and perspective depth cues. The absence of accommodation
      cues can induce two kinds of accommodation vergence mismatches (AVM) at the
      fixation and peripheral points, which can result in severe visual discomfort.
      With the aim of alleviating discomfort arising from AVM, we propose a new visual
      comfort enhancement approach for processing S3D visual signals to deliver a more
      comfortable 3D viewing experience at the display. This is accomplished via an
      optimization process whereby a predictive indicator of visual discomfort is
      minimized, while still aiming to maintain the viewer's sense of 3D presence by
      performing a suitable parallax shift, and by directed blurring of the signal. Our
      processing framework is defined on 3D visual coordinates that reflect the
      nonuniform resolution of retinal sensors and that uses a measure of 3D saliency
      strength. An appropriate level of blur that corresponds to the degree of parallax
      shift is found, making it possible to produce synthetic accommodation cues
      implemented using a perceptively relevant filter. By this method, AVM, the
      primary contributor to the discomfort felt when viewing S3D images, is reduced.
      We show via a series of subjective experiments that the proposed approach
      improves visual comfort while preserving the sense of 3D presence.

PMID- 28499998
TI  - Scalable Image Coding Based on Epitomes.
AB  - In this paper, we propose a novel scheme for scalable image coding based on the
      concept of epitome. An epitome can be seen as a factorized representation of an
      image. Focusing on spatial scalability, the enhancement layer of the proposed
      scheme contains only the epitome of the input image. The pixels of the
      enhancement layer not contained in the epitome are then restored using two
      approaches inspired from local learning-based super-resolution methods. In the
      first method, a locally linear embedding model is learned on base layer patches
      and then applied to the corresponding epitome patches to reconstruct the
      enhancement layer. The second approach learns linear mappings between pairs of co
      located base layer and epitome patches. Experiments have shown that the
      significant improvement of the rate-distortion performances can be achieved
      compared with the Scalable extension of HEVC (SHVC).

PMID- 28499999
TI  - Contrast Enhancement Based on Intrinsic Image Decomposition.
AB  - In this paper, we propose to introduce intrinsic image decomposition priors into
      decomposition models for contrast enhancement. Since image decomposition is a
      highly illposed problem, we introduce constraints on both reflectance and
      illumination layers to yield a highly reliable solution. We regularize the
      reflectance layer to be piecewise constant by introducing a weighted l1 norm
      constraint on neighboring pixels according to the color similarity, so that the
      decomposed reflectance would not be affected much by the illumination
      information. The illumination layer is regularized by a piecewise smoothness
      constraint. The proposed model is effectively solved by the Split Bregman
      algorithm. Then, by adjusting the illumination layer, we obtain the enhancement
      result. To avoid potential color artifacts introduced by illumination adjusting
      and reduce computing complexity, the proposed decomposition model is performed on
      the value channel in HSV space. Experiment results demonstrate that the proposed
      method performs well for a wide variety of images, and achieves better or
      comparable subjective and objective quality compared with the state-of-the-art
      methods.

PMID- 28500000
TI  - Hierarchical Contour Closure-Based Holistic Salient Object Detection.
AB  - Most existing salient object detection methods compute the saliency for pixels,
      patches, or superpixels by contrast. Such fine-grained contrast-based salient
      object detection methods are stuck with saliency attenuation of the salient
      object and saliency overestimation of the background when the image is
      complicated. To better compute the saliency for complicated images, we propose a
      hierarchical contour closure-based holistic salient object detection method, in
      which two saliency cues, i.e., closure completeness and closure reliability, are
      thoroughly exploited. The former pops out the holistic homogeneous regions
      bounded by completely closed outer contours, and the latter highlights the
      holistic homogeneous regions bounded by averagely highly reliable outer contours.
      Accordingly, we propose two computational schemes to compute the corresponding
      saliency maps in a hierarchical segmentation space. Finally, we propose a
      framework to combine the two saliency maps, obtaining the final saliency map.
      Experimental results on three publicly available datasets show that even each
      single saliency map is able to reach the state-of-the-art performance.
      Furthermore, our framework, which combines two saliency maps, outperforms the
      state of the arts. Additionally, we show that the proposed framework can be
      easily used to extend existing methods and further improve their performances
      substantially.

PMID- 28500001
TI  - Exemplar-Based Image and Video Stylization Using Fully Convolutional Semantic
      Features.
AB  - Color and tone stylization in images and videos strives to enhance unique themes
      with artistic color and tone adjustments. It has a broad range of applications
      from professional image postprocessing to photo sharing over social networks.
      Mainstream photo enhancement softwares, such as Adobe Lightroom and Instagram,
      provide users with predefined styles, which are often hand-crafted through a
      trial-and-error process. Such photo adjustment tools lack a semantic
      understanding of image contents and the resulting global color transform limits
      the range of artistic styles it can represent. On the other hand, stylistic
      enhancement needs to apply distinct adjustments to various semantic regions. Such
      an ability enables a broader range of visual styles. In this paper, we first
      propose a novel deep learning architecture for exemplar-based image stylization,
      which learns local enhancement styles from image pairs. Our deep learning
      architecture consists of fully convolutional networks for automatic semantics
      aware feature extraction and fully connected neural layers for adjustment
      prediction. Image stylization can be efficiently accomplished with a single
      forward pass through our deep network. To extend our deep network from image
      stylization to video stylization, we exploit temporal superpixels to facilitate
      the transfer of artistic styles from image exemplars to videos. Experiments on a
      number of data sets for image stylization as well as a diverse set of video clips
      demonstrate the effectiveness of our deep learning architecture.

PMID- 28500002
TI  - Cross-Label Suppression: A Discriminative and Fast Dictionary Learning With Group
      Regularization.
AB  - This paper addresses image classification through learning a compact and
      discriminative dictionary efficiently. Given a structured dictionary with each
      atom (columns in the dictionary matrix) related to some label, we propose
      crosslabel suppression constraint to enlarge the difference among representations
      for different classes. Meanwhile, we introduce group regularization to enforce
      representations to preserve label properties of original samples, meaning the
      representations for the same class are encouraged to be similar. Upon the
      crosslabel suppression, we donot resort to frequently-used l0-norm or l1-norm for
      coding, and obtain computational efficiency without losing the discriminative
      power for categorization. Moreover, two simple classification schemes are also
      developed to take full advantage of the learnt dictionary. Extensive experiments
      on six data sets, including face recognition, object categorization, scene
      classification, texture recognition, and sport action categorization are
      conducted, and the results show that the proposed approach can outperform lots of
      recently presented dictionary algorithms on both recognition accuracy and
      computational efficiency.

PMID- 28500003
TI  - Hybrid Laplace Distribution-Based Low Complexity Rate-Distortion Optimized
      Quantization.
AB  - Rate distortion optimized quantization (RDOQ) is an efficient encoder
      optimization method that plays an important role in improving the rate-distortion
      (RD) performance of the high-efficiency video coding (HEVC) codecs. However, the
      superior performance of RDOQ is achieved at the expense of high computational
      complexity cost in two stages RD minimization, including the determination of
      optimal quantized level among available candidates for each transformed
      coefficient and the determination of best quantized coefficients for transform
      units with the minimum total cost, to softly optimize the quantized coefficients.
      To reduce the computational cost of the RDOQ algorithm in HEVC, we propose a low
      complexity RDOQ scheme by modeling the statistics of the transform coefficients
      with hybrid Laplace distribution. In this manner, specifically designed block
      level rate and distortion models are established based on the coefficient
      distribution. Therefore, the optimal quantization levels can be directly
      determined by optimizing the RD performance of the whole block, while the
      complicated RD cost calculations can be eventually avoided. Extensive
      experimental results show that with about 0.3%-0.4% RD performance degradation,
      the proposed low-complexity RDOQ algorithm is able to reduce around 70%
      quantization time with up to 17% total encoding time reduction compared with the
      original RDOQ implementation in HEVC on average.

PMID- 28500004
TI  - Generic Content-Based Retrieval of Marker-Based Motion Capture Data.
AB  - In this work, we propose an original scheme for generic content-based retrieval
      of marker-based motion capture data. It works on motion capture data of arbitrary
      subject types and arbitrary marker attachment and labelling conventions.
      Specifically, we propose a novel motion signature to statistically describe both
      the high-level and the low-level morphological and kinematic characteristics of a
      motion capture sequence, and conduct the content-based retrieval by computing and
      ordering the motion signature distance between the query and every item in the
      database. The distance between two motion signatures is computed by a weighted
      sum of differences in separate features contained in them. For maximum retrieval
      performance, we propose a method to pre-learn an optimal set of weights for each
      type of motion in the database through biased discriminant analysis, and
      adaptively choose a good set of weights for any given query at the run time.
      Excellence of the proposed scheme is experimentally demonstrated on various data
      sets and performance metrics.

PMID- 28500005
TI  - Patch-Based Image Inpainting via Two-Stage Low Rank Approximation.
AB  - To recover the corrupted pixels, traditional inpainting methods based on low-rank
      priors generally need to solve a convex optimization problem by an iterative
      singular value shrinkage algorithm. In this paper, we propose a simple method for
      image inpainting using low rank approximation, which avoids the time-consuming
      iterative shrinkage. Specifically, if similar patches of a corrupted image are
      identified and reshaped as vectors, then a patch matrix can be constructed by
      collecting these similar patch-vectors. Due to its columns being highly linearly
      correlated, this patch matrix is low-rank. Instead of using an iterative singular
      value shrinkage scheme, the proposed method utilizes low rank approximation with
      truncated singular values to derive a closed-form estimate for each patch matrix.
      Depending upon an observation that there exists a distinct gap in the singular
      spectrum of patch matrix, the rank of each patch matrix is empirically determined
      by a heuristic procedure. Inspired by the inpainting algorithms with component
      decomposition, a two-stage low rank approximation (TSLRA) scheme is designed to
      recover image structures and refine texture details of corrupted images.
      Experimental results on various inpainting tasks demonstrate that the proposed
      method is comparable and even superior to some state-of-the-art inpainting
      algorithms.

PMID- 28500006
TI  - Skill Learning and Skill Transfer Mediated by Cooperative Haptic Interaction.
AB  - It is known that physical coupling between two subjects may be advantageous in
      joint tasks. However, little is known about how two people mutually exchange
      information to exploit the coupling. Therefore, we adopted a reversed, novel
      perspective to the standard one that focuses on the ability of physically coupled
      subjects to adapt to cooperative contexts that require negotiating a common plan:
      we investigated how training in pairs on a novel task affects the development of
      motor skills of each of the interacting partners. The task involved reaching
      movements in an unstable dynamic environment using a bilateral non-linear elastic
      tool that could be used bimanually or dyadically. The main result is that
      training with an expert leads to the greatest performance in the joint task.
      However, the performance in the individual test is strongly affected by the
      initial skill level of the partner. Moreover, practicing with a peer rather than
      an expert appears to be more advantageous for a naive; and motor skills can be
      transferred to a bimanual context, after training with an expert, only if the non
      expert subject had prior experience of the dynamics of the novel task.

PMID- 28500007
TI  - A Wearable Multi-Site System for NMES-Based Hand Function Restoration.
AB  - Reaching and grasping impairments significantly affect the quality of life for
      people who have experienced a stroke or spinal cord injury. The long-term well
      being of patients varies greatly according to the restorable residual
      capabilities. Electrical stimulation could be a promising solution to restore
      motor functions in these conditions, but its use is not clinically widespread.
      Here, we introduce the HandNMES, an electrode array (EA) for neuromuscular
      electrical stimulation (NMES) aimed at grasp training and assistance. The device
      was designed to deliver electrical stimulation to extrinsic and intrinsic hand
      muscles. Six independent EAs, positioned on the user forearm and hand, deliver
      NMES pulses originating from an external stimulator equipped with demultiplexers
      for interfacing with a large number of electrodes. The garment was designed to be
      adaptable to user needs and anthropometric characteristics; size, shape, and
      contact materials can be customized, and stimulation characteristics such as
      intensity of stimulation and virtual electrode location, and size can be
      adjusted. We performed extensive tests with nine healthy subjects showing the
      efficacy of the HandNMES in terms of stimulation performance and personalization.
      Because encouraging results were achieved, in the coming months, the HandNMES
      device will be tested in pilot clinical trials.

PMID- 28500008
TI  - Wearable Haptic Systems for the Fingertip and the Hand: Taxonomy, Review, and
      Perspectives.
AB  - In the last decade, we have witnessed a drastic change in the form factor of
      audio and vision technologies, from heavy and grounded machines to lightweight
      devices that naturally fit our bodies. However, only recently, haptic systems
      have started to be designed with wearability in mind. The wearability of haptic
      systems enables novel forms of communication, cooperation, and integration
      between humans and machines. Wearable haptic interfaces are capable of
      communicating with the human wearers during their interaction with the
      environment they share, in a natural and yet private way. This paper presents a
      taxonomy and review of wearable haptic systems for the fingertip and the hand,
      focusing on those systems directly addressing wearability challenges. The paper
      also discusses the main technological and design challenges for the development
      of wearable haptic interfaces, and it reports on the future perspectives of the
      field. Finally, the paper includes two tables summarizing the characteristics and
      features of the most representative wearable haptic systems for the fingertip and
      the hand.

PMID- 28500009
TI  - End-to-End Feature-Aware Label Space Encoding for Multilabel Classification With
      Many Classes.
AB  - To make the problem of multilabel classification with many classes more
      tractable, in recent years, academia has seen efforts devoted to performing label
      space dimension reduction (LSDR). Specifically, LSDR encodes high-dimensional
      label vectors into low-dimensional code vectors lying in a latent space, so as to
      train predictive models at much lower costs. With respect to the prediction, it
      performs classification for any unseen instance by recovering a label vector from
      its predicted code vector via a decoding process. In this paper, we propose a
      novel method, namely End-to-End Feature-aware label space Encoding (E2FE), to
      perform LSDR. Instead of requiring an encoding function like most previous works,
      E2FE directly learns a code matrix formed by code vectors of the training
      instances in an end-to-end manner. Another distinct property of E2FE is its
      feature awareness attributable to the fact that the code matrix is learned by
      jointly maximizing the recoverability of the label space and the predictability
      of the latent space. Based on the learned code matrix, E2FE further trains
      predictive models to map instance features into code vectors, and also learns a
      linear decoding matrix for efficiently recovering the label vector of any unseen
      instance from its predicted code vector. Theoretical analyses show that both the
      code matrix and the linear decoding matrix in E2FE can be efficiently learned.
      Moreover, similar to previous works, E2FE can be specified to learn an encoding
      function. And it can also be extended with kernel tricks to handle nonlinear
      correlations between the feature space and the latent space. Comprehensive
      experiments conducted on diverse benchmark data sets with many classes show
      consistent performance gains of E2FE over the state-of-the-art methods.

PMID- 28500010
TI  - Robust Latent Subspace Learning for Image Classification.
AB  - This paper proposes a novel method, called robust latent subspace learning
      (RLSL), for image classification. We formulate an RLSL problem as a joint
      optimization problem over both the latent SL and classification model parameter
      predication, which simultaneously minimizes: 1) the regression loss between the
      learned data representation and objective outputs and 2) the reconstruction error
      between the learned data representation and original inputs. The latent subspace
      can be used as a bridge that is expected to seamlessly connect the origin visual
      features and their class labels and hence improve the overall prediction
      performance. RLSL combines feature learning with classification so that the
      learned data representation in the latent subspace is more discriminative for
      classification. To learn a robust latent subspace, we use a sparse item to
      compensate error, which helps suppress the interference of noise via weakening
      its response during regression. An efficient optimization algorithm is designed
      to solve the proposed optimization problem. To validate the effectiveness of the
      proposed RLSL method, we conduct experiments on diverse databases and encouraging
      recognition results are achieved compared with many state-of-the-arts methods.

PMID- 28500011
TI  - Improved Stability and Stabilization Results for Stochastic Synchronization of
      Continuous-Time Semi-Markovian Jump Neural Networks With Time-Varying Delay.
AB  - Continuous-time semi-Markovian jump neural networks (semi-MJNNs) are those MJNNs
      whose transition rates are not constant but depend on the random sojourn time.
      Addressing stochastic synchronization of semi-MJNNs with time-varying delay, an
      improved stochastic stability criterion is derived in this paper to guarantee
      stochastic synchronization of the response systems with the drive systems. This
      is achieved through constructing a semi-Markovian Lyapunov-Krasovskii functional
      together as well as making use of a novel integral inequality and the
      characteristics of cumulative distribution functions. Then, with a linearization
      procedure, controller synthesis is carried out for stochastic synchronization of
      the drive-response systems. The desired state-feedback controller gains can be
      determined by solving a linear matrix inequality-based optimization problem.
      Simulation studies are carried out to demonstrate the effectiveness and less
      conservatism of the presented approach.

PMID- 28500012
TI  - Memcomputing Numerical Inversion With Self-Organizing Logic Gates.
AB  - We propose to use digital memcomputing machines (DMMs), implemented with self
      organizing logic gates (SOLGs), to solve the problem of numerical inversion.
      Starting from fixed-point scalar inversion, we describe the generalization to
      solving linear systems and matrix inversion. This method, when realized in
      hardware, will output the result in only one computational step. As an example,
      we perform simulations of the scalar case using a 5-bit logic circuit made of
      SOLGs, and show that the circuit successfully performs the inversion. Our method
      can be extended efficiently to any level of precision, since we prove that
      producing -bit precision in the output requires extending the circuit by at most
      bits. This type of numerical inversion can be implemented by DMM units in
      hardware; it is scalable, and thus of great benefit to any real-time computing
      application.

PMID- 28500013
TI  - New Splitting Criteria for Decision Trees in Stationary Data Streams.
AB  - The most popular tools for stream data mining are based on decision trees. In
      previous 15 years, all designed methods, headed by the very fast decision tree
      algorithm, relayed on Hoeffding's inequality and hundreds of researchers followed
      this scheme. Recently, we have demonstrated that although the Hoeffding decision
      trees are an effective tool for dealing with stream data, they are a purely
      heuristic procedure; for example, classical decision trees such as ID3 or CART
      cannot be adopted to data stream mining using Hoeffding's inequality. Therefore,
      there is an urgent need to develop new algorithms, which are both mathematically
      justified and characterized by good performance. In this paper, we address this
      problem by developing a family of new splitting criteria for classification in
      stationary data streams and investigating their probabilistic properties. The new
      criteria, derived using appropriate statistical tools, are based on the
      misclassification error and the Gini index impurity measures. The general
      division of splitting criteria into two types is proposed. Attributes chosen
      based on type- splitting criteria guarantee, with high probability, the highest
      expected value of split measure. Type- criteria ensure that the chosen attribute
      is the same, with high probability, as it would be chosen based on the whole
      infinite data stream. Moreover, in this paper, two hybrid splitting criteria are
      proposed, which are the combinations of single criteria based on the
      misclassification error and Gini index.

PMID- 28500014
TI  - Three-Dimensional Visual Patient Based on Electronic Medical Diagnostic Records.
AB  - OBJECTIVE: an innovative concept and method is introduced to use a 3-D anatomical
      graphic pattern called visual patient (VP) visually to index, represent, and
      render the medical diagnostic records (MDRs) of a patient, so that a doctor can
      quickly learn the current and historical medical status of the patient by
      manipulating VP. The MDRs can be imaging diagnostic reports and DICOM images,
      laboratory reports and clinical summaries which can have clinical information
      relating to medical status of human organs or body parts. METHODS: the concept
      and method included three steps. First, a VP data model called visual index
      object (VIO) and a VP graphic model called visual anatomic object (VAO) were
      introduced. Second, a series of processing methods of parsing and extracting key
      information from MDRs were used to fill the attributes of the VIO model of a
      patient. Third, a VP system (VPS) was designed to map VIO to VAO, to create a VP
      instance for each patient. RESULTS: a prototype VPS has been implemented in a
      simulated hospital PACS/RIS integrated environment. Two evaluation results showed
      that more than 70% participating radiologists would like to use the VPS in their
      radiological imaging tasks, and the efficiency of using VPS to review the tested
      patients' MDRs was 2.24 times higher than that of using PACS/RIS, while the
      average accuracy <Pac> by using PACS/RIS was better than that by using VPS;
      however, this difference was only about 4%. CONCLUSION: the developed VPS can
      show the medical status of patient organs/sub-organs with 3-D anatomical graphic
      pattern and will be welcomed by radiologists with better efficiency in reviewing
      the patients' MDRs and with acceptable accuracy. SIGNIFICANCE: the VP introduces
      a new way for medical professionals to access and interact with a huge amount of
      patient records with better efficiency in the big data era.

PMID- 28500015
TI  - Social Synchrony on Complex Networks.
AB  - Social synchrony (SS) is an emergent phenomenon in human society. People often
      mimic others which, over time, can result in large groups behaving similarly.
      Drawing from prior empirical studies of SS in online communities, here we propose
      a discrete network model of SS based on four attributes: 1) depth of action; 2)
      breadth of impact, i.e., a large number of actions are performed with a large
      group of people involved; 3) heterogeneity of role, i.e., people of higher degree
      play more important roles; and 4) lastly, emergence of phenomenon, i.e., it is
      far from random. We analyze our model both analytically and with simulations, and
      find good agreement between the two. We find this model can well explain the four
      characters of SS, and thus hope it can help researchers better understand human
      collective behavior.

PMID- 28500016
TI  - Adaptive Graph Matching.
AB  - Establishing correspondence between point sets lays the foundation for many
      computer vision and pattern recognition tasks. It can be well defined and solved
      by graph matching. However, outliers may significantly deteriorate its
      performance, especially when outliers exist in both point sets and meanwhile the
      inlier number is unknown. In this paper, we propose an adaptive graph matching
      algorithm to tackle this problem. Specifically, a novel formulation is proposed
      to make the graph matching model adaptively determine the number of inliers and
      match them, then by relaxing the discrete domain to its convex hull the discrete
      optimization problem is relaxed to be a continuous one, and finally a graduated
      projection scheme is used to get a discrete matching solution. Consequently, the
      proposed algorithm could realize inlier number estimation, inlier selection, and
      inlier matching in one optimization framework. Experiments on both synthetic data
      and real world images witness the effectiveness of the proposed algorithm.

PMID- 28500017
TI  - Tablet-Based Well-Being Check for the Elderly: Development and Evaluation of
      Usability and Acceptability.
AB  - BACKGROUND: Many elderly people prefer to live at home independently. One of the
      major concerns raised by the family members is the safety and well-being of their
      elderly family members when living independently in a home environment. To
      address this issue, assistive technology solutions have been available in the
      market. Despite their availability and proliferation, these types of solutions
      are not popular with the elderly due to their intrusive nature, privacy-related
      issues, social stigma, and fear of losing human interaction. This study shares
      the experience in the development of a digital photo frame system that helps
      family members to check the well-being of the elderly, exploiting their desire to
      remain socially connected. OBJECTIVES: The aim of this study was to iteratively
      design, implement, and assess the usability, user friendliness, and acceptability
      of a tablet-based system to check the well-being of the elderly. METHODS: Our
      study methodology comprises three separate stages: initial system development,
      contextual assessment, and comparative case study evaluation. RESULTS: In the
      first stage, requirements were elicited from the elderly to design a well-being
      check prototype. In the second stage, areas for improvements (eg, privacy
      features) were identified. Also, additional features (such as medication prompts
      or food reminders) were suggested to help aged and health care service providers
      with effective but subtle monitoring of the elderly. These would lower their
      operating cost by reducing visits by care providers to the homes of the elderly.
      In the third stage, the results highlighted the difference (between users in
      India and Australia) in the levels of familiarity of the elderly with this
      technology. Some elderly participants at the Kalyani Institute for Study,
      Planning and Action for Rural Change, India latched onto this technology quickly
      while a few refused to use the system. However, in all cases, the support of
      family members was crucial for their willingness to use the technology.
      CONCLUSIONS: This project has three major outcomes. First, a picture frame
      prototype was tested with the elderly to leverage the benefits of social
      communication. Second, the project helped us test and implement the "Silvercare"
      model for supporting the elderly through young retired people residing in the
      area. Finally, the project helped formalize the agile three-stage design
      methodology to develop information technology solutions for the elderly. Also,
      the project contributed to an ongoing European Union Project called Victoryahome,
      which involves more than 50 sites across 5 countries (Norway, Sweden,
      Netherlands, Portugal, and Australia) to assess the use of telepresence robots,
      wearable fall detectors, and medication dispensers for the elderly living
      independently.

PMID- 28500018
TI  - Guidelines for the Gamification of Self-Management of Chronic Illnesses:
      Multimethod Study.
AB  - BACKGROUND: Gamification is the use of game elements and techniques in nongaming
      contexts. The use of gamification in health care is receiving a great deal of
      attention in both academic research and the industry. However, it can be noticed
      that many gamification apps in health care do not follow any standardized
      guidelines. OBJECTIVE: This research aims to (1) present a set of guidelines
      based on the validated framework the Wheel of Sukr and (2) assess the guidelines
      through expert interviews and focus group sessions with developers. METHODS:
      Expert interviews (N=6) were conducted to assess the content of the guidelines
      and that they reflect the Wheel of Sukr. In addition, the guidelines were
      assessed by developers (N=15) in 5 focus group sessions, where each group had an
      average of 3 developers. RESULTS: The guidelines received support from the
      experts. By the end of the sixth interview, it was determined that a saturation
      point was reached. Experts agreed that the guidelines accurately reflect the
      framework the Wheel of Sukr and that developers can potentially use them to
      create gamified self-management apps for chronic illnesses. Moreover, the
      guidelines were welcomed by developers who participated in the focus group
      sessions. They found the guidelines to be clear, useful, and implementable. Also,
      they were able to suggest many ways of gamifying a nongamified self-management
      app when they were presented with one. CONCLUSIONS: The findings suggest that the
      guidelines introduced in this research are clear, useful, and ready to be
      implemented for the creation of self-management apps that use the notion of
      gamification as described in the Wheel of Sukr framework. The guidelines are now
      ready to be practically tested. Further practical studies of the effectiveness of
      each element in the guidelines are to be carried out.

PMID- 28500019
TI  - Assessing the Comparability of Paper and Electronic Versions of the EORTC QOL
      Module for Head and Neck Cancer: A Qualitative Study.
AB  - BACKGROUND: Patient-reported outcome (PRO) instruments are important tools for
      monitoring disease activity and response to treatment in clinical trials and
      clinical practice. In recent years, there have been movements away from
      traditional pen-and-paper PROs towards electronic administration. When using
      electronic PROs (ePROs), evidence that respondents complete ePROs in a similar
      way to their paper counterparts provides assurance that the two modes of
      administration are comparable or equivalent. The European Organisation for
      Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30
      item (EORTC QLQ-C30) and associated disease-specific modules are among the most
      widely used PROs in oncology. Although studies have evaluated the comparability
      and equivalence of electronic and original paper versions of the EORTC QLQ-C30,
      no such studies have been conducted to date for the head and neck cancer specific
      module (EORTC QLQ-H&N35). OBJECTIVE: This study aimed to qualitatively assess the
      comparability of paper and electronic versions of the EORTC QLQ-H&N35. METHODS:
      Ten head and neck cancer patients in the United States underwent structured
      cognitive debriefing and usability interviews. An open randomized crossover
      design was used in which participants completed the two modes of administration
      allocated in a randomized order. Using a "think-aloud" process, participants were
      asked to speak their thoughts aloud while completing the EORTC QLQ-H&N35. They
      were thoroughly debriefed on their responses to determine consistency in
      interpretation and cognitive process when completing the instrument in both paper
      and electronic format. RESULTS: Participants reported that the EORTC QLQ-H&N35
      demonstrated excellent qualitative comparability between modes of administration.
      The proportion of noncomparable responses (ie, where the thought process used by
      participants for selecting responses appeared to be different) observed in the
      study was low (11/350 response pairs [35 items x 10 participants]; 3.1%).
      Evidence of noncomparability was observed for 9 of the 35 items of the EORTC QLQ
      H&N35 and in no more than 2 participants per item. In addition, there were no
      apparent differences in level of comparability between individual participants or
      between modes of administration. CONCLUSIONS: Mode of administration does not
      affect participants' response to, or interpretation of, items in the EORTC QLQ
      H&N35. The findings from this study add to the existing evidence supporting the
      use of electronic versions of the EORTC instruments when migrated to electronic
      platforms according to best practice guidelines.

PMID- 28500021
TI  - Thoracic Surgery Information on the Internet: A Multilingual Quality Assessment.
AB  - BACKGROUND: Previous data suggest that quality of Internet information regarding
      surgical conditions and their treatments is variable. However, no comprehensive
      analysis of website quality exists for thoracic surgery. OBJECTIVE: The aim of
      this study was to quantify website quality in a multilingual setting using an
      international standard for assessment. METHODS: Health On the Net (HON)
      principles may be applied to websites using an automated toolbar function. We
      used the English, French, Spanish, and German Google search engines to identify
      12,000 websites using keywords related to thoracic conditions and procedures. The
      first 150 websites returned by each keyword in each language were examined. We
      compared website quality to assess for tertile (is the quality better in first,
      second, or third 50 websites returned) and language differences. A further
      analysis of the English site types was undertaken performing a comparative
      analysis of website provider types. RESULTS: Overall, there are a considerable
      number of websites devoted to thoracic surgery: "lung cancer" returned over 150
      million websites. About 7.85% (940/11,967) of websites are HON-accredited with
      differences by search term (P<.001) and tertiles (P<.001) of the first 150
      websites, but not between languages. Oncological keywords regarding conditions
      and procedures were found to return a higher percentage of HON-accreditation. The
      percentage of HON-accredited sites was similar across all four languages (P=.77).
      In general, the first tertile contained a higher percentage of HON-accredited
      sites for every keyword. CONCLUSIONS: Clinicians should appreciate the lack of
      validation of the majority of thoracic websites, with discrepancies in quality
      and number of websites across conditions and procedures. These differences appear
      similar regardless of language. An opportunity exists for clinicians to
      participate in the development of informative, ethical, and reliable health
      websites on the Internet and direct patients to them.

PMID- 28500023
TI  - An apparently simple case of fever and sore throat.

PMID- 28500024
TI  - Anticancer Sulfonamides Induce Splicing Factor RBM39 Degradation.
AB  - Anticancer sulfonamides produce aberrant splicing by inducing degradation of the
      splicing factor RBM39.

PMID- 28500020
TI  - Efficacy of a Web-Based Guided Recommendation Service for a Curated List of
      Readily Available Mental Health and Well-Being Mobile Apps for Young People:
      Randomized Controlled Trial.
AB  - BACKGROUND: Mental disorders are highly prevalent for the people who are aged
      between 16 and 25 years and can permanently disrupt the development of these
      individuals. Easily available mobile health (mHealth) apps for mobile phones have
      great potential for the prevention and early intervention of mental disorders in
      young adults, but interventions are required that can help individuals to both
      identify high-quality mobile apps and use them to change health and lifestyle
      behavior. OBJECTIVES: The study aimed to assess the efficacy of a Web-based self
      guided app recommendation service ("The Toolbox") in improving the well-being of
      young Australians aged between 16 and 25 years. The intervention was developed in
      collaboration with young adults and consists of a curated list of 46 readily
      available health and well-being apps, assessed and rated by professionals and
      young people. Participants are guided by an interactive quiz and subsequently
      receive recommendations for particular apps to download and use based on their
      personal goals. METHODS: The study was a waitlist, parallel-arm, randomized
      controlled trial. Our primary outcome measure was change in well-being as
      measured by the Mental Health Continuum-Short Form (MHC-SF). We also employed
      ecological momentary assessments (EMAs) to track mood, energy, rest, and sleep.
      Participants were recruited from the general Australian population, via several
      Web-based and community strategies. The study was conducted through a Web-based
      platform consisting of a landing Web page and capabilities to administer study
      measures at different time points. Web-based measurements were self-assessed at
      baseline and 4 weeks, and EMAs were collected repeatedly at regular weekly
      intervals or ad hoc when participants interacted with the study platform. Primary
      outcomes were analyzed using linear mixed-models and intention-to-treat (ITT)
      analysis. RESULTS: A total of 387 participants completed baseline scores and were
      randomized into the trial. Results demonstrated no significant effect of "The
      Toolbox" intervention on participant well-being at 4 weeks compared with the
      control group (P=.66). There were also no significant differences between the
      intervention and control groups at 4 weeks on any of the subscales of the MHC-SF
      (psychological: P=.95, social: P=.42, emotional: P=.95). Repeat engagement with
      the study platform resulted in a significant difference in mood, energy, rest,
      and sleep trajectories between intervention and control groups as measured by
      EMAs (P<.01). CONCLUSIONS: This was the first study to assess the effectiveness
      of a Web-based well-being intervention in a sample of young adults. The design of
      the intervention utilized expert rating of existing apps and end-user codesign
      approaches resulting in an app recommendation service. Our finding suggests that
      recommended readily available mental health and well-being apps may not lead to
      improvements in the well-being of a nonclinical sample of young people, but might
      halt a decline in mood, energy, rest, and sleep. TRIAL REGISTRATION: Australian
      New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614000710628;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366145 (Archived
      by WebCite at http://www.webcitation.org/ 6pWDsnKme).

PMID- 28500022
TI  - What Matters in Weight Loss? An In-Depth Analysis of Self-Monitoring.
AB  - BACKGROUND: Using technology to self-monitor body weight, dietary intake, and
      physical activity is a common practice used by consumers and health companies to
      increase awareness of current and desired behaviors in weight loss. Understanding
      how to best use the information gathered by these relatively new methods needs to
      be further explored. OBJECTIVE: The purpose of this study was to analyze the
      contribution of self-monitoring to weight loss in participants in a 6-month
      commercial weight-loss intervention administered by Retrofit and to specifically
      identify the significant contributors to weight loss that are associated with
      behavior and outcomes. METHODS: A retrospective analysis was performed using 2113
      participants enrolled from 2011 to 2015 in a Retrofit weight-loss program.
      Participants were males and females aged 18 years or older with a starting body
      mass index of >=25 kg/m2, who also provided a weight measurement at the sixth
      month of the program. Multiple regression analysis was performed using all
      measures of self-monitoring behaviors involving weight measurements, dietary
      intake, and physical activity to predict weight loss at 6 months. Each
      significant predictor was analyzed in depth to reveal the impact on outcome.
      RESULTS: Participants in the Retrofit Program lost a mean -5.58% (SE 0.12) of
      their baseline weight with 51.87% (1096/2113) of participants losing at least 5%
      of their baseline weight. Multiple regression model (R2=.197, P<0.001) identified
      the following measures as significant predictors of weight loss at 6 months:
      number of weigh-ins per week (P<.001), number of steps per day (P=.02), highly
      active minutes per week (P<.001), number of food log days per week (P<.001), and
      the percentage of weeks with five or more food logs (P<.001). Weighing in at
      least three times per week, having a minimum of 60 highly active minutes per
      week, food logging at least three days per week, and having 64% (16.6/26) or more
      weeks with at least five food logs were associated with clinically significant
      weight loss for both male and female participants. CONCLUSIONS: The self
      monitoring behaviors of self-weigh-in, daily steps, high-intensity activity, and
      persistent food logging were significant predictors of weight loss during a 6
      month intervention.

PMID- 28500027
TI  - Engineering CAR T Cells with Biomaterials.
AB  - Incorporating biomaterials into the design of CAR T cells may yield new, improved
      versions of this immunotherapy. Two preclinical studies indicate the potential of
      using biodegradable nanoparticles to program circulating T cells into CAR T cells
      in situ, and delivering these therapeutic cells directly to solid tumors via
      small dissolvable sponges.

PMID- 28500030
TI  - Translating Divergent Environmental Stresses into a Common Proteome Response
      through Hik33 in a Model Cyanobacterium.
AB  - The histidine kinase Hik33 plays important roles in mediating cyanobacterial
      response to divergent types of abiotic stresses including cold, salt, high light
      (HL), and osmotic stresses. However, how these functions are regulated by Hik33
      remains to be addressed. Using a hik33-deficient strain (Deltahik33) of
      Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found
      that Hik33 depletion induces differential protein expression highly similar to
      that induced by divergent types of stresses. This typically includes
      downregulation of proteins in photosynthesis and carbon assimilation that are
      necessary for cell propagation, and upregulation of heat shock proteins,
      chaperons, and proteases that are important for cell survival. This observation
      indicates that depletion of Hik33 alone mimics divergent types of abiotic
      stresses, and that Hik33 could be important for preventing abnormal stress
      response in the normal condition. Moreover, we found the majority of proteins of
      plasmid origin were significantly upregulated in Deltahik33, though their
      biological significance remains to be addressed. Together, the systematically
      characterized Hik33-regulated cyanobacterial proteome, which is largely involved
      in stress responses, builds the molecular basis for Hik33 as a general regulator
      of stress responses.

PMID- 28500031
TI  - Labeling glycans on living cells by a chemoenzymatic glycoengineering approach.
AB  - Structural glycobiology has traditionally been a challenging field due to a
      limited set of tools available to investigate the diverse and complex glycan
      molecules. However, we cannot ignore that glycans play critical roles in health
      as well as in disease, and are present in more than 50% of all proteins and on
      over 80% of all surface proteins. Chemoenzymatic glycoengineering (CGE) methods
      are a powerful set of tools to synthesize complex glycans, but the full potential
      of these methods have not been explored in cell biology yet. Herein, we report
      the labeling of live Chinese hamster ovary (CHO) cells by employing three highly
      specific glycosyltransferases: a sialyltransferase, a galactosyltransferase, and
      an N-acetyl-glucosaminyl transferase. We verified our results by bio-orthogonal
      blots and further rationalized them by computational modeling. We expect CGE
      applications in cell biology to rise and their implementation will assist in
      structural-functional discoveries in glycobiology. This research will contribute
      to this effort.

PMID- 28500032
TI  - Senescence gives insights into the morphogenetic evolution of anamniotes.
AB  - Senescence represents a mechanism to avoid undesired cell proliferation that
      plays a role in tumor suppression, wound healing and embryonic development. In
      order to gain insight on the evolution of senescence, we looked at its presence
      in developing axolotls (urodele amphibians) and in zebrafish (teleost fish),
      which are both anamniotes. Our data indicate that cellular senescence is present
      in various developing structures in axolotls (pronephros, olfactory epithelium of
      nerve fascicles, lateral organs, gums) and in zebrafish (epithelium of the yolk
      sac and in the lower part of the gut). Senescence was particularly associated
      with transient structures (pronephros in axolotls and yolk sac in zebrafish)
      suggesting that it may play a role in the elimination of these tissues. Our data
      supports the notion that cellular senescence evolved early in vertebrate
      evolution to influence embryonic development.

PMID- 28500034
TI  - Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease.

PMID- 28500033
TI  - Proteomic responses to elevated ocean temperature in ovaries of the ascidian
      Ciona intestinalis.
AB  - Ciona intestinalis, a common sea squirt, exhibits lower reproductive success at
      the upper extreme of the water temperatures it experiences in coastal New
      England. In order to understand the changes in protein expression associated with
      elevated temperatures, and possible response to global temperature change, we
      reared C. intestinalis from embryos to adults at 18 degrees C (a temperature at
      which they reproduce normally at our collection site in Rhode Island) and 22
      degrees C (the upper end of the local temperature range). We then dissected
      ovaries from animals at each temperature, extracted protein, and measured
      proteomic levels using shotgun mass spectrometry (LC-MS/MS). 1532 proteins were
      detected at a 1% false discovery rate present in both temperature groups by our
      LC-MS/MS method. 62 of those proteins are considered up- or down-regulated
      according to our statistical criteria. Principal component analysis shows a clear
      distinction in protein expression pattern between the control (18 degrees C)
      group and high temperature (22 degrees C) group. Similar to previous studies,
      cytoskeletal and chaperone proteins are upregulated in the high temperature
      group. Unexpectedly, we find evidence that proteolysis is downregulated at the
      higher temperature. We propose a working model for the high temperature response
      in C. intestinalis ovaries whereby increased temperature induces upregulation of
      signal transduction pathways involving PTPN11 and CrkL, and activating
      coordinated changes in the proteome especially in large lipid transport proteins,
      cellular stress responses, cytoskeleton, and downregulation of energy metabolism.

PMID- 28500035
TI  - Montgomery and informed consent: where are we now?

PMID- 28500036
TI  - Heritability and risks associated with early onset hypertension:
      multigenerational, prospective analysis in the Framingham Heart Study.
AB  - Objective To determine the role of early onset versus late onset hypertension as
      a risk factor for hypertension in offspring and cardiovascular death.Design
      Multigenerational, prospective cohort study.Setting Framingham Heart
      Study.Participants Two generations of community dwelling participants with blood
      pressure measurements performed at serial examinations spanning six decades: 3614
      first generation participants with mortality data and 1635 initially non
      hypertensive second generation participants with data available on parental blood
      pressure.Main outcome measures The main outcome measures were relation of
      parental early onset hypertension (age <55 years) with incidence of hypertension
      in offspring, using regression analyses, and relation of age at hypertension
      onset with cause specific mortality using a case (cardiovascular death) versus
      control (non-cardiovascular death) design.Results In second generation
      participants, having one or both parents with late onset hypertension did not
      increase the risk of hypertension compared with having parents with no
      hypertension; by contrast, the hazard ratios of hypertension were 2.0 (95%
      confidence interval 1.2 to 3.5) and 3.5 (1.9 to 6.1) in participants with one and
      both parents with early onset hypertension, respectively. In first generation
      decedents, 1151 cardiovascular deaths occurred (including 630 coronary deaths).
      The odds of cardiovascular death increased linearly with decreasing age of
      hypertension onset (P<0.001 for trend). Compared with non-hypertensive
      participants, hypertension onset at age <45 years conferred an odds ratios of 2.2
      (1.8 to 2.7) for cardiovascular death and 2.3 (1.8 to 2.9) for coronary death,
      whereas hypertension onset at age >=65 years conferred a lower magnitude odds
      ratios of 1.5 (1.2 to 1.9) for cardiovascular death and 1.4 (0.98 to 1.9) for
      coronary death (P<=0.002 for differences in odds ratios between hypertension
      onset at age <45 and age >=65).Conclusions Early onset and not late onset
      hypertension in parents was strongly associated with hypertension in offspring.
      In turn, early onset compared with late onset hypertension was associated with
      greater odds of cardiovascular, and particularly coronary, death. These findings
      suggest it may be important to distinguish between early onset and late onset
      hypertension as a familial trait when assessing an individual's risk for
      hypertension, and as a specific type of blood pressure trait when estimating risk
      for cardiovascular outcomes in adults with established hypertension.

PMID- 28500037
TI  - Improving Baculovirus Infectivity by Efficiently Embedding Enhancing Factors into
      Occlusion Bodies.
AB  - The relatively low infectivity of baculoviruses to their host larvae limits their
      use as insecticidal agents on a larger scale. In the present study, a novel
      strategy was developed to efficiently embed foreign proteins into Autographa
      californica multiple nucleopolyhedrovirus (AcMNPV) occlusion bodies (OBs) to
      achieve stable expression of foreign proteins and to improve viral infectivity. A
      recombinant AcMNPV bacmid was constructed by expressing the 150-amino-acid (aa) N
      terminal segment of polyhedrin under the control of the p10 promoter and the
      remaining C-terminal 95-aa segment under the control of the polyhedrin promoter.
      The recombinant virus formed OBs in Spodoptera frugiperda 9 cells, in which the
      occlusion-derived viruses were embedded in a manner similar to that for wild-type
      AcMNPV. Next, the 95-aa polyhedrin C terminus was fused to enhanced green
      fluorescent protein, and the recombinant AcMNPV formed fluorescent green OBs and
      was stably passaged in vitro and in vivo The AcMNPV recombinants were further
      modified by fusing truncated Agrotis segetum granulovirus enhancin or truncated
      Cydia pomonella granulovirus ORF13 (GP37) to the C-terminal 95 aa of polyhedrin,
      and both recombinants were able to form normal OBs. Bioactivity assays indicated
      that the median lethal concentrations of these two AcMNPV recombinants were 3- to
      5-fold lower than that of the control virus. These results suggest that embedding
      enhancing factors in baculovirus OBs by use of this novel technique may promote
      efficient and stable foreign protein expression and significantly improve
      baculovirus infectivity.IMPORTANCE Baculoviruses have been used as
      bioinsecticides for over 40 years, but their relatively low infectivity to their
      host larvae limits their use on a larger scale. It has been reported that it is
      possible to improve baculovirus infectivity by packaging enhancing factors within
      baculovirus occlusion bodies (OBs); however, so far, the packaging efficiency has
      been low. In this article, we describe a novel strategy for efficiently embedding
      foreign proteins into AcMNPV OBs by expressing N- and C-terminal (dimidiate)
      polyhedrin fragments (150 and 95 amino acids, respectively) as fusions to foreign
      proteins under the control of the p10 and polyhedrin promoters, respectively.
      When this strategy was used to embed an enhancing factor (enhancin or GP37) into
      the baculovirus OBs, 3- to 5-fold increases in baculoviral infectivity were
      observed. This novel strategy has the potential to create an efficient protein
      expression system and a highly efficient virus-based system for insecticide
      production in the future.

PMID- 28500038
TI  - Enrichment and Physiological Characterization of a Cold-Adapted Nitrite-Oxidizing
      Nitrotoga sp. from an Eelgrass Sediment.
AB  - Nitrite-oxidizing bacteria (NOB) are responsible for the second step of
      nitrification in natural and engineered ecosystems. The recently discovered genus
      Nitrotoga belongs to the Betaproteobacteria and potentially has high
      environmental importance. Although environmental clones affiliated with Nitrotoga
      are widely distributed, the limited number of cultivated Nitrotoga spp. results
      in a poor understanding of their ecophysiological features. In this study, we
      successfully enriched the nonmarine cold-adapted Nitrotoga sp. strain AM1 from
      coastal sand in an eelgrass zone and investigated its physiological
      characteristics. Multistep-enrichment approaches led to an increase in the
      abundance of AM1 to approximately 80% of the total bacterial population. AM1 was
      the only detectable NOB in the bacterial community. The 16S rRNA gene sequence of
      AM1 was 99.6% identical to that of "Candidatus Nitrotoga arctica," which was
      enriched from permafrost-affected soil. The highest nitrogen oxidation rate of
      AM1 was observed at 16 degrees C. The half-saturation constant (Km ) and the
      generation time were determined to be 25 MUM NO2- and 54 h, respectively. The
      nitrite oxidation rate of AM1 was stimulated at concentrations of <30 mM NH4Cl
      but completely inhibited at 50 mM NH4Cl. AM1 can grow well under specific
      environmental conditions, such as low temperature and in the presence of a
      relatively high concentration of free ammonia. These results help improve our
      comprehension of the functional importance of NitrotogaIMPORTANCE Nitrite
      oxidizing bacteria (NOB) are key players in the second step of nitrification,
      which is an important process of the nitrogen cycle. Recent studies have
      suggested that the organisms of the novel NOB genus Nitrotoga were widely
      distributed and played a functional role in natural and engineered ecosystems.
      However, only a few Nitrotoga enrichments have been obtained, and little is known
      about their ecology and physiology. In this study, we successfully enriched a
      Nitrotoga sp. from sand in a shallow coastal marine ecosystem and undertook a
      physiological characterization. The laboratory experiments showed that the
      Nitrotoga enrichment culture could adapt not only to low temperature but also to
      relatively high concentrations of free ammonia. The determination of as-yet
      unknown unique characteristics of Nitrotoga contributes to the improvement of our
      insights into the microbiology of nitrification.

PMID- 28500039
TI  - Selected Probiotic Lactobacilli Have the Capacity To Hydrolyze Gluten Peptides
      during Simulated Gastrointestinal Digestion.
AB  - The aim of this study was to demonstrate the capacity of probiotic lactobacilli
      to hydrolyze immunogenic gluten peptides. Eighteen commercial strains of
      probiotic lactobacilli with highly variable peptidase activity (i.e.,
      aminopeptidase N, iminopeptidase, prolyl endopeptidyl peptidase, tripeptidase,
      prolidase, prolinase, and dipeptidase), including toward Pro-rich peptides, were
      tested in this study. Ten probiotic strains were selected on the basis of their
      specific enzyme activity. When pooled, these 10 strains provided the peptidase
      portfolio that is required to completely degrade the immunogenic gluten peptides
      involved in celiac disease (CD). The selected probiotic mixture was able to
      completely hydrolyze well-known immunogenic epitopes, including the gliadin 33
      mer peptide, the peptide spanning residues 57 to 68 of the alpha9-gliadin (alpha9
      gliadin peptide 57-68), A-gliadin peptide 62-75, and gamma-gliadin peptide 62-75.
      During digestion under simulated gastrointestinal conditions, the pool of 10
      selected probiotic lactobacilli strongly hydrolyzed the wheat bread gluten (ca.
      18,000 ppm) to less than 10 ppm after 360 min of treatment. As determined by
      multidimensional chromatography (MDLC) coupled to nanoelectrospray ionization
      (nano-ESI)-tandem mass spectrometry (MS/MS), no known immunogenic peptides were
      detected in wheat bread that was digested in the presence of the probiotics.
      Accordingly, the level of cytokines (interleukin 2 [IL-2], IL-10, and interferon
      gamma [IFN-gamma]) produced by duodenal biopsy specimens from CD patients who
      consumed wheat bread digested by probiotics was similar to the baseline value
      (negative control). Probiotics that specifically hydrolyze gluten polypeptides
      could also be used to hydrolyze immunogenic peptides that contaminate gluten-free
      products. This could provide a new and safe adjunctive therapy alternative to the
      gluten-free diet (GFD).IMPORTANCE This study confirmed that probiotic
      Lactobacillus strains have different enzymatic abilities for hydrolyzing
      polypeptides, including the Pro-rich epitopes involved in the pathology of CD.
      Ten lactobacilli with complementary peptidase activities that hydrolyze gluten
      peptides during simulated gastrointestinal digestion were selected and tested.
      The results collected showed the potential of probiotic formulas as novel dietary
      treatments for CD patients.

PMID- 28500040
TI  - Novel Sampling Method for Assessing Human-Pathogen Interactions in the Natural
      Environment Using Boot Socks and Citizen Scientists, with Application to
      Campylobacter Seasonality.
AB  - This paper introduces a novel method for sampling pathogens in natural
      environments. It uses fabric boot socks worn over walkers' shoes to allow the
      collection of composite samples over large areas. Wide-area sampling is better
      suited to studies focusing on human exposure to pathogens (e.g., recreational
      walking). This sampling method is implemented using a citizen science approach:
      groups of three walkers wearing boot socks undertook one of six routes, 40 times
      over 16 months in the North West (NW) and East Anglian (EA) regions of England.
      To validate this methodology, we report the successful implementation of this
      citizen science approach, the observation that Campylobacter bacteria were
      detected on 47% of boot socks, and the observation that multiple boot socks from
      individual walks produced consistent results. The findings indicate higher
      Campylobacter levels in the livestock-dominated NW than in EA (55.8% versus
      38.6%). Seasonal differences in the presence of Campylobacter bacteria were found
      between the regions, with indications of winter peaks in both regions but a
      spring peak in the NW. The presence of Campylobacter bacteria on boot socks was
      negatively associated with ambient temperature (P = 0.011) and positively
      associated with precipitation (P < 0.001), results consistent with our
      understanding of Campylobacter survival and the probability of material adhering
      to boot socks. Campylobacter jejuni was the predominant species found;
      Campylobacter coli was largely restricted to the livestock-dominated NW. Source
      attribution analysis indicated that the potential source of C. jejuni was
      predominantly sheep in the NW and wild birds in EA but did not differ between
      peak and nonpeak periods of human incidence.IMPORTANCE There is debate in the
      literature on the pathways through which pathogens are transferred from the
      environment to humans. We report on the success of a novel method for sampling
      human-pathogen interactions using boot socks and citizen science techniques,
      which enable us to sample human-pathogen interactions that may occur through
      visits to natural environments. This contrasts with traditional environmental
      sampling, which is based on spot sampling techniques and does not sample human
      pathogen interactions. Our methods are of practical value to scientists trying to
      understand the transmission of pathogens from the environment to people. Our
      findings provide insight into the risk of Campylobacter exposure from
      recreational visits and an understanding of seasonal differences in risk and the
      factors behind these patterns. We highlight the Campylobacter species
      predominantly encountered and the potential sources of C. jejuni.

PMID- 28500041
TI  - Real-Time PCR Method for Detection of Salmonella spp. in Environmental Samples.
AB  - The methods currently used for detecting Salmonella in environmental samples
      require 2 days to produce results and have limited sensitivity. Here, we describe
      the development and validation of a real-time PCR Salmonella screening method
      that produces results in 18 to 24 h. Primers and probes specific to the gene
      invA, group D, and Salmonella enterica serovar Enteritidis organisms were
      designed and evaluated for inclusivity and exclusivity using a panel of 329
      Salmonella isolates representing 126 serovars and 22 non-Salmonella organisms.
      The invA- and group D-specific sets identified all the isolates accurately. The
      PCR method had 100% inclusivity and detected 1 to 2 copies of Salmonella DNA per
      reaction. Primers specific for Salmonella-differentiating fragment 1 (Sdf-1) in
      conjunction with the group D set had 100% inclusivity for 32 S Enteritidis
      isolates and 100% exclusivity for the 297 non-Enteritidis Salmonella isolates.
      Single-laboratory validation performed on 1,741 environmental samples
      demonstrated that the PCR method detected 55% more positives than the Vitek
      immunodiagnostic assay system (VIDAS) method. The PCR results correlated well
      with the culture results, and the method did not report any false-negative
      results. The receiver operating characteristic (ROC) analysis documented
      excellent agreement between the results from the culture and PCR methods (area
      under the curve, 0.90; 95% confidence interval of 0.76 to 1.0) confirming the
      validity of the PCR method.IMPORTANCE This validated PCR method detects 55% more
      positives for Salmonella in half the time required for the reference method,
      VIDAS. The validated PCR method will help to strengthen public health efforts
      through rapid screening of Salmonella spp. in environmental samples.

PMID- 28500042
TI  - Carboxyl Analogue of Mutacin 1140, a Scaffold for Lead Antibacterial Discovery.
AB  - Mutacin 1140 belongs to the epidermin group of lantibiotics. Epidermin class
      lantibiotics are ribosomally synthesized and posttranslationally modified
      antibiotics with potent activity against Gram-positive bacteria. In particular,
      this class is effective at targeting drug-resistant Streptococcus pneumoniae,
      methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis,
      and Clostridium difficile A C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys)
      residue is derived from a decarboxylation of a terminal cysteine that is involved
      in lanthionine ring formation. Studies on mutacin 1140 have revealed new insight
      into the structural importance of the C-terminal AviCys residue. A C-terminal
      carboxyl analogue of mutacin 1140 was engineered. Capping the C-terminal carboxyl
      group with a primary amine restores bioactivity and affords a novel opportunity
      to synthesize new analogues. A C-terminal fluorescein-labeled mutacin 1140
      analogue traps lipid II into a large lipid II lantibiotic complex, similar to
      that observed in vivo for the lantibiotic nisin. A C-terminal carboxyl analogue
      of mutacin 1140 competitively inhibits the activity of native mutacin 1140 and
      nisin. The presence of a C-terminal carboxyl group prevents the formation of the
      large lipid II lantibiotic complexes but does not prevent the binding of the
      lantibiotic to lipid II.IMPORTANCE This study addressed the importance of the C
      terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) residue for antibacterial
      activity. We have learned that the posttranslational modification for making the
      AviCys residue is presumably important for the lateral assembly mechanism of
      activity that traps lipid II into a large complex. The C-terminal carboxyl
      analogue of this class of lantibiotics is agreeable to the addition of a wide
      variety of substrates. The addition of fluorescein enabled in vivo visualization
      of the epidermin class of lantibiotics in action. These results are significant
      because, as we demonstrate, the presence of the AviCys residue is not essential
      for bioactivity, but, more importantly, the removal of the carboxyl group is
      essential. The ability to make a C-terminal carboxyl analogue that is modifiable
      will facilitate the synthesis of novel analogues of the epidermin class of
      lantibiotics that can be developed for new applications.

PMID- 28500043
TI  - Potential for Waterborne and Invertebrate Transmission of West Nile Virus in the
      Great Salt Lake, Utah.
AB  - In November and December of 2013, a large mortality event involving 15,000 to
      20,000 eared grebes (Podiceps nigricollis) occurred at the Great Salt Lake (GSL),
      UT. The onset of the outbreak in grebes was followed by a mortality event in >86
      bald eagles (Haliaeetus leucocephalus). During the die-off, West Nile virus (WNV)
      was detected by reverse transcription-PCR (RT-PCR) or viral culture in the
      carcasses of grebes and eagles submitted to the National Wildlife Health Center.
      However, no activity of mosquitoes, the primary vectors of WNV, was detected by
      the State of Utah's WNV monitoring program. The transmission of WNV has rarely
      been reported during the winter in North America in the absence of known mosquito
      activity; however, the size of this die-off, the habitat in which it occurred,
      and the species involved are unique. We experimentally investigated whether WNV
      could survive in water with a high salt content, as found at the GSL, and whether
      brine shrimp, the primary food of migrating eared grebes on the GSL, could have
      played a role in the transmission of WNV to feeding birds. We found that WNV can
      survive up to 72 h at 4 degrees C in water containing 30 to 150 ppt NaCl, and
      brine shrimp incubated with WNV in 30 ppt NaCl may adsorb WNV to their cuticle
      and, through feeding, infect epithelial cells of their gut. Both mechanisms may
      have potentiated the WNV die-off in migrating eared grebes on the GSL.IMPORTANCE
      Following a major West Nile virus die-off of eared grebes and bald eagles at the
      Great Salt Lake (GSL), UT, in November to December 2013, this study assessed the
      survival of West Nile virus (WNV) in water as saline as that of the GSL and
      whether brine shrimp, the major food for migrating grebes, could have played a
      role as a vector for the virus. While mosquitoes are the major vector of WNV,
      under certain circumstances, transmission may occur through contaminated water
      and invertebrates as food.

PMID- 28500044
TI  - RpoN (sigma54) Is Required for Floc Formation but Not for Extracellular
      Polysaccharide Biosynthesis in a Floc-Forming Aquincola tertiaricarbonis Strain.
AB  - Some bacteria are capable of forming flocs, in which bacterial cells become self
      flocculated by secreted extracellular polysaccharides and other biopolymers. The
      floc-forming bacteria play a central role in activated sludge, which has been
      widely utilized for the treatment of municipal sewage and industrial wastewater.
      Here, we use a floc-forming bacterium, Aquincolatertiaricarbonis RN12, as a model
      to explore the biosynthesis of extracellular polysaccharides and the regulation
      of floc formation. A large gene cluster for exopolysaccharide biosynthesis and a
      gene encoding the alternative sigma factor RpoN1, one of the four paralogues,
      have been identified in floc formation-deficient mutants generated by transposon
      mutagenesis, and the gene functions have been further confirmed by genetic
      complementation analyses. Interestingly, the biosynthesis of exopolysaccharides
      remained in the rpoN1-disrupted flocculation-defective mutants, but most of the
      exopolysaccharides were secreted and released rather than bound to the cells.
      Furthermore, the expression of exopolysaccharide biosynthesis genes seemed not to
      be regulated by RpoN1. Taken together, our results indicate that RpoN1 may play a
      role in regulating the expression of a certain gene(s) involved in the self
      flocculation of bacterial cells but not in the biosynthesis and secretion of
      exopolysaccharides required for floc formation.IMPORTANCE Floc formation confers
      bacterial resistance to predation of protozoa and plays a central role in the
      widely used activated sludge process. In this study, we not only identified a
      large gene cluster for biosynthesis of extracellular polysaccharides but also
      identified four rpoN paralogues, one of which (rpoN1) is required for floc
      formation in A. tertiaricarbonis RN12. In addition, this RpoN sigma factor
      regulates the transcription of genes involved in biofilm formation and swarming
      motility, as previously shown in other bacteria. However, this RpoN paralogue is
      not required for the biosynthesis of exopolysaccharides, which are released and
      dissolved into culture broth by the rpoN1 mutant rather than remaining tightly
      bound to cells, as observed during the flocculation of the wild-type strain.
      These results indicate that floc formation is a regulated complex process, and
      other yet-to-be identified RpoN1-dependent factors are involved in self
      flocculation of bacterial cells via exopolysaccharides and/or other biopolymers.

PMID- 28500045
TI  - Sodium Lactate Negatively Regulates Shewanella putrefaciens CN32 Biofilm
      Formation via a Three-Component Regulatory System (LrbS-LrbA-LrbR).
AB  - The capability of biofilm formation has a major impact on the industrial and
      biotechnological applications of Shewanella putrefaciens CN32. However, the
      detailed regulatory mechanisms underlying biofilm formation in this strain remain
      largely unknown. In the present report, we describe a three-component regulatory
      system which negatively regulates the biofilm formation of S. putrefaciens CN32.
      This system consists of a histidine kinase LrbS (Sputcn32_0303) and two cognate
      response regulators, including a transcription factor, LrbA (Sputcn32_0304), and
      a phosphodiesterase, LrbR (Sputcn32_0305). LrbS responds to the signal of the
      carbon source sodium lactate and subsequently activates LrbA. The activated LrbA
      then promotes the expression of lrbR, the gene for the other response regulator.
      The bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) phosphodiesterase LrbR, containing
      an EAL domain, decreases the concentration of intracellular c-di-GMP, thereby
      negatively regulating biofilm formation. In summary, the carbon source sodium
      lactate acts as a signal molecule that regulates biofilm formation via a three
      component regulatory system (LrbS-LrbA-LrbR) in S. putrefaciens CN32.IMPORTANCE
      Biofilm formation is a significant capability used by some bacteria to survive in
      adverse environments. Numerous environmental factors can affect biofilm formation
      through different signal transduction pathways. Carbon sources are critical
      nutrients for bacterial growth, and their concentrations and types significantly
      influence the biomass and structure of biofilms. However, knowledge about the
      underlying mechanism of biofilm formation regulation by carbon source is still
      limited. This work elucidates a modulation pattern of biofilm formation
      negatively regulated by sodium lactate as a carbon source via a three-component
      regulatory system in S. putrefaciens CN32, which may serve as a good example for
      studying how the carbon sources impact biofilm development in other bacteria.

PMID- 28500046
TI  - RoxB Is a Novel Type of Rubber Oxygenase That Combines Properties of Rubber
      Oxygenase RoxA and Latex Clearing Protein (Lcp).
AB  - Only two types of rubber oxygenases, rubber oxygenase (RoxA) and latex clearing
      protein (Lcp), have been described so far. RoxA proteins (RoxAs) are c-type
      cytochromes of ~70 kDa produced by Gram-negative rubber-degrading bacteria, and
      they cleave polyisoprene into 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD), a
      C15 oligo-isoprenoid, as the major end product. Lcps are common among Gram
      positive rubber degraders and do not share amino acid sequence similarities with
      RoxAs. Furthermore, Lcps have much smaller molecular masses (~40 kDa), are b-type
      cytochromes, and cleave polyisoprene to a mixture of C20, C25, C30, and higher
      oligo-isoprenoids as end products. In this article, we purified a new type of
      rubber oxygenase, RoxB Xsp (RoxB of Xanthomonas sp. strain 35Y). RoxB Xsp is
      distantly related to RoxAs and resembles RoxAs with respect to molecular mass
      (70.3 kDa for mature protein) and cofactor content (2 c-type hemes). However,
      RoxB Xsp differs from all currently known RoxAs in having a distinctive product
      spectrum of C20, C25, C30, and higher oligo-isoprenoids that has been observed
      only for Lcps so far. Purified RoxB Xsp revealed the highest specific activity of
      4.5 U/mg (at 23 degrees C) of all currently known rubber oxygenases and exerts a
      synergistic effect on the efficiency of polyisoprene cleavage by RoxA Xsp RoxB
      homologs were identified in several other Gram-negative rubber-degrading species,
      pointing to a prominent function of RoxB for the biodegradation of rubber in Gram
      negative bacteria.IMPORTANCE The enzymatic cleavage of rubber (polyisoprene) is
      of high environmental importance given that enormous amounts of rubber waste
      materials are permanently released (e.g., by abrasion of tires). Research from
      the last decade has discovered rubber oxygenase A, RoxA, and latex clearing
      protein (Lcp) as being responsible for the primary enzymatic attack on the
      hydrophobic and water-insoluble biopolymer poly(cis-1,4-isoprene) in Gram
      negative and Gram-positive rubber-degrading bacteria, respectively. Here, we
      provide evidence that a third type of rubber oxygenase is present in Gram
      negative rubber-degrading species. Due to its characteristics, we suggest the
      designation RoxB for the new type of rubber oxygenase. Bioinformatic analysis of
      genome sequences indicates the presence of roxB homologs in other Gram-negative
      rubber degraders.

PMID- 28500048
TI  - Insight into the Recent Genome Duplication of the Halophilic Yeast Hortaea
      werneckii: Combining an Improved Genome with Gene Expression and Chromatin
      Structure.
AB  - Extremophilic organisms demonstrate the flexibility and adaptability of basic
      biological processes by highlighting how cell physiology adapts to environmental
      extremes. Few eukaryotic extremophiles have been well studied and only a small
      number are amenable to laboratory cultivation and manipulation. A detailed
      characterization of the genome architecture of such organisms is important to
      illuminate how they adapt to environmental stresses. One excellent example of a
      fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina,
      Dothideomycetes, Capnodiales), a yeast-like fungus able to thrive at near
      saturating concentrations of sodium chloride and which is also tolerant to both
      UV irradiation and desiccation. Given its unique lifestyle and its remarkably
      recent whole genome duplication, H. werneckii provides opportunities for testing
      the role of genome duplications and adaptability to extreme environments. We
      previously assembled the genome of H. werneckii using short-read sequencing
      technology and found a remarkable degree of gene duplication. Technology
      limitations, however, precluded high-confidence annotation of the entire genome.
      We therefore revisited the H. wernickii genome using long-read, single-molecule
      sequencing and provide an improved genome assembly which, combined with
      transcriptome and nucleosome analysis, provides a useful resource for fungal
      halophile genomics. Remarkably, the ~50 Mb H. wernickii genome contains 15,974
      genes of which 95% (7608) are duplicates formed by a recent whole genome
      duplication (WGD), with an average of 5% protein sequence divergence between
      them. We found that the WGD is extraordinarily recent, and compared to
      Saccharomyces cerevisiae, the majority of the genome's ohnologs have not diverged
      at the level of gene expression of chromatin structure.

PMID- 28500047
TI  - Self-reactive VH4-34-expressing IgG B cells recognize commensal bacteria.
AB  - The germline immunoglobulin (Ig) variable heavy chain 4-34 (VH4-34) gene segment
      encodes in humans intrinsically self-reactive antibodies that recognize I/i
      carbohydrates expressed by erythrocytes with a specific motif in their framework
      region 1 (FWR1). VH4-34-expressing clones are common in the naive B cell
      repertoire but are rarely found in IgG memory B cells from healthy individuals.
      In contrast, CD27+IgG+ B cells from patients genetically deficient for IRAK4 or
      MYD88, which mediate the function of Toll-like receptors (TLRs) except TLR3,
      contained VH4-34-expressing clones and showed decreased somatic hypermutation
      frequencies. In addition, VH4-34-encoded IgGs from IRAK4- and MYD88-deficient
      patients often displayed an unmutated FWR1 motif, revealing that these antibodies
      still recognize I/i antigens, whereas their healthy donor counterparts harbored
      FWR1 mutations abolishing self-reactivity. However, this paradoxical self
      reactivity correlated with these VH4-34-encoded IgG clones binding commensal
      bacteria antigens. Hence, B cells expressing germline-encoded self-reactive VH4
      34 antibodies may represent an innate-like B cell population specialized in the
      containment of commensal bacteria when gut barriers are breached.

PMID- 28500049
TI  - Metabolic Adaptation to Nutrients Involves Coregulation of Gene Expression by the
      RNA Helicase Dbp2 and the Cyc8 Corepressor in Saccharomyces cerevisiae.
AB  - Cells fine-tune their metabolic programs according to nutrient availability in
      order to maintain homeostasis. This is achieved largely through integrating
      signaling pathways and the gene expression program, allowing cells to adapt to
      nutritional change. Dbp2, a member of the DEAD-box RNA helicase family in
      Saccharomyces cerevisiae, has been proposed to integrate gene expression with
      cellular metabolism. Prior work from our laboratory has reported the necessity of
      DBP2 in proper gene expression, particularly for genes involved in glucose
      dependent regulation. Here, by comparing differentially expressed genes in dbp2?
      to those of 700 other deletion strains from other studies, we find that CYC8 and
      TUP1, which form a complex and inhibit transcription of numerous genes, corepress
      a common set of genes with DBP2 Gene ontology (GO) annotations reveal that these
      corepressed genes are related to cellular metabolism, including respiration,
      gluconeogenesis, and alternative carbon-source utilization genes. Consistent with
      a direct role in metabolic gene regulation, loss of either DBP2 or CYC8 results
      in increased cellular respiration rates. Furthermore, we find that corepressed
      genes have a propensity to be associated with overlapping long noncoding RNAs and
      that upregulation of these genes in the absence of DBP2 correlates with decreased
      binding of Cyc8 to these gene promoters. Taken together, this suggests that Dbp2
      integrates nutrient availability with energy homeostasis by maintaining
      repression of glucose-repressed, Cyc8-targeted genes across the genome.

PMID- 28500051
TI  - Effects of the Ordering of Natural Selection and Population Regulation Mechanisms
      on Wright-Fisher Models.
AB  - We explore the effect of different mechanisms of natural selection on the
      evolution of populations for one- and two-locus systems. We compare the effect of
      viability and fecundity selection in the context of the Wright-Fisher model with
      selection under the assumption of multiplicative fitness. We show that these two
      modes of natural selection correspond to different orderings of the processes of
      population regulation and natural selection in the Wright-Fisher model. We find
      that under the Wright-Fisher model these two different orderings can affect the
      distribution of trajectories of haplotype frequencies evolving with genetic
      recombination. However, the difference in the distribution of trajectories is
      only appreciable when the population is in significant linkage disequilibrium. We
      find that as linkage disequilibrium decays the trajectories for the two different
      models rapidly become indistinguishable. We discuss the significance of these
      findings in terms of biological examples of viability and fecundity selection,
      and speculate that the effect may be significant when factors such as gene
      migration maintain a degree of linkage disequilibrium.

PMID- 28500050
TI  - A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation
      Patterns for Complex Disease.
AB  - Integrating diverse genomics data can provide a global view of the complex
      biological processes related to the human complex diseases. Although substantial
      efforts have been made to integrate different omics data, there are at least
      three challenges for multi-omics integration methods: (i) How to simultaneously
      consider the effects of various genomic factors, since these factors jointly
      influence the phenotypes; (ii) How to effectively incorporate the information
      from publicly accessible databases and omics datasets to fully capture the
      interactions among (epi)genomic factors from diverse omics data; and (iii) Until
      present, the combination of more than two omics datasets has been poorly
      explored. Current integration approaches are not sufficient to address all of
      these challenges together. We proposed a novel integrative analysis framework by
      incorporating sparse model, multivariate analysis, Gaussian graphical model, and
      network analysis to address these three challenges simultaneously. Based on this
      strategy, we performed a systemic analysis for glioblastoma multiforme (GBM)
      integrating genome-wide gene expression, DNA methylation, and miRNA expression
      data. We identified three regulatory modules of genomic factors associated with
      GBM survival time and revealed a global regulatory pattern for GBM by combining
      the three modules, with respect to the common regulatory factors. Our method can
      not only identify disease-associated dysregulated genomic factors from different
      omics, but more importantly, it can incorporate the information from publicly
      accessible databases and omics datasets to infer a comprehensive interaction map
      of all these dysregulated genomic factors. Our work represents an innovative
      approach to enhance our understanding of molecular genomic mechanisms underlying
      human complex diseases.

PMID- 28500052
TI  - Exploring the Impact of Cleavage and Polyadenylation Factors on Pre-mRNA Splicing
      Across Eukaryotes.
AB  - In human, mouse, and Drosophila, the spliceosomal complex U1 snRNP (U1) protects
      transcripts from premature cleavage and polyadenylation at proximal intronic
      polyadenylation signals (PAS). These U1-mediated effects preserve transcription
      integrity, and are known as telescripting. The watchtower role of U1 throughout
      transcription is clear. What is less clear is whether cleavage and
      polyadenylation factors (CPFs) are simply patrolled or if they might actively
      antagonize U1 recruitment. In addressing this question, we found that, in the
      introns of human, mouse, and Drosophila, and of 14 other eukaryotes, including
      multi- and single-celled species, the conserved AATAAA PAS-a major target for
      CPFs-is selected against. This selective pressure, approximated using DNA strand
      asymmetry, is detected for peripheral and internal introns alike. Surprisingly,
      it is more pronounced within-rather than outside-the action range of
      telescripting, and particularly intense in the vicinity of weak 5' splice sites.
      Our study uncovers a novel feature of eukaryotic genes: that the AATAAA PAS is
      universally counter-selected in spliceosomal introns. This pattern implies that
      CPFs may attempt to access introns at any time during transcription. However,
      natural selection operates to minimize this access. By corroborating and
      extending previous work, our study further indicates that CPF access to intronic
      PASs might perturb the recruitment of U1 to the adjacent 5' splice sites. These
      results open the possibility that CPFs may impact the splicing process across
      eukaryotes.

PMID- 28500053
TI  - Manipulating the Mitochondrial Genome To Enhance Cattle Embryo Development.
AB  - The mixing of mitochondrial DNA (mtDNA) from the donor cell and the recipient
      oocyte in embryos and offspring derived from somatic cell nuclear transfer (SCNT)
      compromises genetic integrity and affects embryo development. We set out to
      generate SCNT embryos that inherited their mtDNA from the recipient oocyte only,
      as is the case following natural conception. While SCNT blastocysts produced from
      Holstein (Bos taurus) fibroblasts depleted of their mtDNA, and oocytes derived
      from Angus (Bos taurus) cattle possessed oocyte mtDNA only, the coexistence of
      donor cell and oocyte mtDNA resulted in blastocysts derived from nondepleted
      cells. Moreover, the use of the reprogramming agent, Trichostatin A (TSA),
      further improved the development of embryos derived from depleted cells. RNA-seq
      analysis highlighted 35 differentially expressed genes from the comparison
      between blastocysts generated from nondepleted cells and blastocysts from
      depleted cells, both in the presence of TSA. The only differences between these
      two sets of embryos were the presence of donor cell mtDNA, and a significantly
      higher mtDNA copy number for embryos derived from nondepleted cells. Furthermore,
      the use of TSA on embryos derived from depleted cells positively modulated the
      expression of CLDN8, TMEM38A, and FREM1, which affect embryonic development. In
      conclusion, SCNT embryos produced by mtDNA depleted donor cells have the same
      potential to develop to the blastocyst stage without the presumed damaging effect
      resulting from the mixture of donor and recipient mtDNA.

PMID- 28500054
TI  - Linkage Map of Lissotriton Newts Provides Insight into the Genetic Basis of
      Reproductive Isolation.
AB  - Linkage maps are widely used to investigate structure, function, and evolution of
      genomes. In speciation research, maps facilitate the study of the genetic
      architecture of reproductive isolation by allowing identification of genomic
      regions underlying reduced fitness of hybrids. Here we present a linkage map for
      European newts of the Lissotriton vulgaris species complex, constructed using two
      families of F2 L. montandoni * L. vulgaris hybrids. The map consists of 1146
      protein-coding genes on 12 linkage groups, equal to the haploid chromosome
      number, with a total length of 1484 cM (1.29 cM per marker). It is notably
      shorter than two other maps available for salamanders, but the differences in map
      length are consistent with cytogenetic estimates of the number of chiasmata per
      chromosomal arm. Thus, large salamander genomes do not necessarily translate into
      long linkage maps, as previously suggested. Consequently, salamanders are an
      excellent model to study evolutionary consequences of recombination rate
      variation in taxa with large genomes and a similar number of chromosomes. A
      complex pattern of transmission ratio distortion (TRD) was detected: TRD occurred
      mostly in one family, in one breeding season, and was clustered in two genomic
      segments. This is consistent with environment-dependent mortality of individuals
      carrying L. montandoni alleles in these two segments and suggests a role of TRD
      blocks in reproductive isolation. The reported linkage map will empower studies
      on the genomic architecture of divergence and interactions between the genomes of
      hybridizing newts.

PMID- 28500056
TI  - A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia.
AB  - Ascertaining the molecular and physiological basis of domestication and breeding
      is an active area of research. Due to the current wide distribution of its wild
      ancestor, the wild boar, the pig (Sus scrofa) is an excellent model to study
      these processes, which occurred independently in East Asia and Europe ca. 9000 yr
      ago. Analyzing genome variability patterns in terms of metabolic pathways is
      attractive since it considers the impact of interrelated functions of genes, in
      contrast to genome-wide scans that treat genes or genome windows in isolation. To
      that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and
      Europe when metabolic pathway was the unit of analysis. We computed statistical
      significance for differentiation (Fst) and linkage disequilibrium (nSL)
      statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways
      significantly differentiated at a q-value < 0.05 in Asia and Europe,
      respectively; five were shared across continents. In Asia, we found six
      significant pathways related to behavior, which involved essential
      neurotransmitters like dopamine and serotonin. Several significant pathways were
      interrelated and shared a variable percentage of genes. There were 12 genes
      present in >10 significant pathways (in terms of Fst), comprising genes involved
      in the transduction of a large number of signals, like phospholipase PCLB1, which
      is expressed in the brain, or ITPR3, which has an important role in taste
      transduction. In terms of nSL, significant pathways were mainly related to
      reproductive performance (ovarian steroidogenesis), a similarly important target
      trait during domestication and modern animal breeding. Different levels of
      recombination cannot explain these results, since we found no correlation between
      Fst and recombination rate. However, we did find an increased ratio of
      deleterious mutations in domestic vs. wild populations, suggesting a relaxed
      functional constraint associated with the domestication and breeding processes.
      Purifying selection was, nevertheless, stronger in significantly differentiated
      pathways than in random pathways, mainly in Europe. We conclude that pathway
      analysis facilitates the biological interpretation of genome-wide studies.
      Notably, in the case of pig, behavior played an important role, among other
      physiological and developmental processes.

PMID- 28500055
TI  - RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating
      Eye and Neuromuscular Junction Morphology.
AB  - Accumulation of toxic proteins in neurons has been linked with the onset of
      neurodegenerative diseases, which in many cases are characterized by altered
      neuronal function and synapse loss. Molecular chaperones help protein folding and
      the resolubilization of unfolded proteins, thereby reducing the protein
      aggregation stress. While most of the chaperones are expressed in neurons, their
      functional relevance remains largely unknown. Here, using bioinformatics
      analysis, we identified 95 Drosophila chaperones and classified them into seven
      different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that
      ~50% of the chaperones are essential in Drosophila Knocking down these genes in
      eyes revealed that ~30% of the essential chaperones are crucial for eye
      development. Using neuron-specific knockdown, immunocytochemistry, and robust
      behavioral assays, we identified a new set of chaperones that play critical roles
      in the regulation of Drosophila NMJ structural organization. Together, our data
      present the first classification and comprehensive analysis of Drosophila
      chaperones. Our screen identified a new set of chaperones that regulate eye and
      NMJ morphogenesis. The outcome of the screen reported here provides a useful
      resource for further elucidating the role of individual chaperones in Drosophila
      eye morphogenesis and synaptic development.

PMID- 28500058
TI  - Response to: 'HLA-A* 31:01 is not associated with the development of methotrexate
      pneumonitis in the UK population: results from a genome wide association study'
      by Bluett et al.

PMID- 28500057
TI  - HLA-A 31:01 is not associated with the development of methotrexate pneumonitis in
      the UK population: results from a genome-wide association study.

PMID- 28500059
TI  - Toothpick impaction in a sigmoid diverticulum.
AB  - A 70-year-old woman presented to our emergency department with recurrent episodes
      of left lower quadrant pain. She subsequently underwent high anterior resection
      with working diagnosis of acute diverticulitis, but intraoperatively was found to
      have perforated sigmoid diverticulum due to toothpick impaction. A high index of
      suspicion is required for diagnosis of toothpick ingestion. Appropriate
      preoperative investigations such as endoscopy and CT, despite their fairly low
      sensitivity, should be performed to increase the ability to accurately diagnose
      this condition and therefore optimise subsequent management.

PMID- 28500060
TI  - Unusual presentation of right coronary artery fistula.

PMID- 28500061
TI  - Abdominal electroacupuncture demonstrates an increase in complete spontaneous
      bowel movements.

PMID- 28500062
TI  - Possible protective effect of prenatal omega-3 long-chain polyunsaturated fatty
      acids supplementation on persistent wheeze and asthma in early childhood.

PMID- 28500063
TI  - Oral antibiotics are as effective as intravenous antibiotics for postdischarge
      treatment of complicated pneumonia in children.

PMID- 28500064
TI  - Cry presence and amplitude do not reflect cortical processing of painful stimuli
      in newborns with distinct responses to touch or cold.
AB  - OBJECTIVE: Newborns requiring hospitalisation frequently undergo painful
      procedures. Prevention of pain in infants is of prime concern because of adverse
      associations with physiological and neurological development. However, pain
      mitigation is currently guided by behavioural observation assessments that have
      not been validated against direct evidence of pain processing in the brain. The
      aim of this study was to determine whether cry presence or amplitude is a valid
      indicator of pain processing in newborns. DESIGN: Prospective observational
      cohort. SETTING: Newborn nursery. PATIENTS: Healthy infants born at >37 weeks and
      <42 weeks gestation. INTERVENTIONS: We prospectively studied newborn cortical
      responses to light touch, cold and heel stick, and the amplitude of associated
      infant vocalisations using our previously published paradigms of time-locked
      electroencephalogram (EEG) with simultaneous audio recordings. RESULTS: Latencies
      of cortical peak responses to each of the three stimuli type were significantly
      different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had
      cries in response to light touch, cold and heel stick, respectively. Cry in
      response to non-painful stimuli did not predict cry in response to heel stick.
      All infants with EEG data had measurable pain responses to heel stick, whether
      they cried or not. There was no association between presence or amplitude of
      cries and cortical nociceptive amplitudes. CONCLUSIONS: In newborns with distinct
      brain responses to light touch, cold and pain, cry presence or amplitude
      characteristics do not provide adequate behavioural markers of pain signalling in
      the brain. New bedside assessments of newborn pain may need to be developed using
      brain-based methodologies as benchmarks in order to provide optimal pain
      mitigation.

PMID- 28500066
TI  - Classic Spotlight, 1988 and 1989: Articles of Significant Interest Selected from
      the Journal of Virology Archives by the Editors.

PMID- 28500068
TI  - The first CT in a SAH: a picture tells a story.
AB  - Finding the cause of acute neurological deterioration in the hours following
      aneurysmal subarachnoid haemorrhage remains challenging. The presence of blood
      casts in the ventricles proves that deterioration is secondary to acute
      hydrocephalus and prompts immediate external ventricular drain placement.

PMID- 28500065
TI  - Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset
      hydrocephalus in mice.
AB  - Hydrocephalus is a common congenital anomaly. LCAM1 and MPDZ (MUPP1) are the only
      known human gene loci associated with non-syndromic hydrocephalus. To investigate
      functions of the tight junction-associated protein Mpdz, we generated mouse
      models. Global Mpdz gene deletion or conditional inactivation in Nestin-positive
      cells led to formation of supratentorial hydrocephalus in the early postnatal
      period. Blood vessels, epithelial cells of the choroid plexus, and cilia on
      ependymal cells, which line the ventricular system, remained morphologically
      intact in Mpdz-deficient brains. However, flow of cerebrospinal fluid through the
      cerebral aqueduct was blocked from postnatal day 3 onward. Silencing of Mpdz
      expression in cultured epithelial cells impaired barrier integrity, and loss of
      Mpdz in astrocytes increased RhoA activity. In Mpdz-deficient mice, ependymal
      cells had morphologically normal tight junctions, but expression of the
      interacting planar cell polarity protein Pals1 was diminished and barrier
      integrity got progressively lost. Ependymal denudation was accompanied by
      reactive astrogliosis leading to aqueductal stenosis. This work provides a
      relevant hydrocephalus mouse model and demonstrates that Mpdz is essential to
      maintain integrity of the ependyma.

PMID- 28500070
TI  - CXCR3.1 and CXCR3.2 Differentially Contribute to Macrophage Polarization in
      Teleost Fish.
AB  - The study of multiple copies of chemokine receptor genes in various teleosts has
      long appealed to investigators seeking to understand the evolution of the immune
      system. The CXCR CXCR3 gene has two isoforms, CXCR3.1 and CXCR3.2, which are both
      expressed in macrophages. The distinct roles of teleost CXCR3s have not been
      identified previously. In this article, we found that CXCR3.1 and CXCR3.2
      differentially contributed to macrophage polarization in the teleosts: ayu
      (Plecoglossus altivelis), grass carp (Ctenopharyngodon idella), and spotted green
      pufferfish (Tetraodon nigroviridis). In ayu macrophages, the P. altivelis CXCR3.1
      (PaCXCR3.1) gene was constitutively expressed, whereas the P. altivelis CXCR3.2
      (PaCXCR3.2) gene was induced postinfection with Escherichia coli Upon E. coli
      infection, PaCXCR3.1+ and PaCXCR3.2+ macrophages showed an M1 and an M2
      phenotype, respectively. CXCL9-11-like proteins mediated M1 and M2 polarization
      by interacting with the PaCXCR3.1 and PaCXCR3.2 proteins on macrophages,
      respectively. The transcription factors P. altivelis STAT1 and P. altivelis STAT3
      were activated in PaCXCR3.1+ and PaCXCR3.2+ macrophages, respectively.
      Furthermore, the prognosis of septic ayu adoptively transferred with PaCXCR3.2+
      macrophages was improved. Our data reveal a previously unknown mechanism for
      macrophage polarization, suggesting that redundant genes may regulate crucial
      functions in the teleost immune system.

PMID- 28500069
TI  - B Cell Activity Is Impaired in Human and Mouse Obesity and Is Responsive to an
      Essential Fatty Acid upon Murine Influenza Infection.
AB  - Obesity is associated with increased risk for infections and poor responses to
      vaccinations, which may be due to compromised B cell function. However, there is
      limited information about the influence of obesity on B cell function and
      underlying factors that modulate B cell responses. Therefore, we studied B cell
      cytokine secretion and/or Ab production across obesity models. In obese humans, B
      cell IL-6 secretion was lowered and IgM levels were elevated upon ex vivo anti
      BCR/TLR9 stimulation. In murine obesity induced by a high fat diet, ex vivo IgM
      and IgG were elevated with unstimulated B cells. Furthermore, the high fat diet
      lowered bone marrow B cell frequency accompanied by diminished transcripts of
      early lymphoid commitment markers. Murine B cell responses were subsequently
      investigated upon influenza A/Puerto Rico/8/34 infection using a Western diet
      model in the absence or presence of docosahexaenoic acid (DHA). DHA, an essential
      fatty acid with immunomodulatory properties, was tested because its plasma levels
      are lowered in obesity. Relative to controls, mice consuming the Western diet had
      diminished Ab titers whereas the Western diet plus DHA improved titers.
      Mechanistically, DHA did not directly target B cells to elevate Ab levels.
      Instead, DHA increased the concentration of the downstream specialized
      proresolving lipid mediators (SPMs) 14-hydroxydocosahexaenoic acid, 17
      hydroxydocosahexaenoic acid, and protectin DX. All three SPMs were found to be
      effective in elevating murine Ab levels upon influenza infection. Collectively,
      the results demonstrate that B cell responses are impaired across human and mouse
      obesity models and show that essential fatty acid status is a factor influencing
      humoral immunity, potentially through an SPM-mediated mechanism.

PMID- 28500071
TI  - Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin
      3, and Mer Tyrosine Kinase.
AB  - Activated microglia can phagocytose dying, stressed, or excess neurons and
      synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal
      3) can cross-link surface glycoproteins by binding galactose residues that are
      normally hidden below terminal sialic acid residues. Gal-3 was recently reported
      to opsonize cells via activating MerTK. We found that LPS-activated BV-2
      microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors.
      Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and
      it increased microglial phagocytosis of PC12 cells or primary neurons, which was
      blocked by inhibition of MerTK. LPS-activated microglia exhibited a sialidase
      activity that desialylated PC12 cells and could be inhibited by Tamiflu, a
      neuraminidase (sialidase) inhibitor. Sialidase treatment of PC12 cells enabled
      Gal-3 to bind and opsonize the live cells for phagocytosis by microglia. LPS
      induced microglial phagocytosis of PC12 was prevented by small interfering RNA
      knockdown of Gal-3 in microglia, lactose inhibition of Gal-3 binding, inhibition
      of neuraminidase with Tamiflu, or inhibition of MerTK by UNC569. LPS-induced
      phagocytosis of primary neurons by primary microglia was also blocked by
      inhibition of MerTK. We conclude that activated microglia release Gal-3 and a
      neuraminidase that desialylates microglial and PC12 surfaces, enabling Gal-3
      binding to PC12 cells and their phagocytosis via MerTK. Thus, Gal-3 acts as an
      opsonin of desialylated surfaces, and inflammatory loss of neurons or synapses
      may potentially be blocked by inhibiting neuraminidases, Gal-3, or MerTK.

PMID- 28500072
TI  - The Upregulation of Integrin alphaDbeta2 (CD11d/CD18) on Inflammatory Macrophages
      Promotes Macrophage Retention in Vascular Lesions and Development of
      Atherosclerosis.
AB  - Macrophage accumulation is a critical step during development of chronic
      inflammation, initiating progression of many devastating diseases. Leukocyte
      specific integrin alphaDbeta2 (CD11d/CD18) is dramatically upregulated on
      macrophages at inflammatory sites. Previously we found that CD11d overexpression
      on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In
      this study, we have investigated how inflammation-mediated CD11d upregulation
      contributes to macrophage retention at inflammatory sites during atherogenesis.
      Atherosclerosis was evaluated in CD11d-/-/ApoE-/- mice after 16 wk on a Western
      diet. CD11d deficiency led to a marked reduction in lipid deposition in aortas
      and isolated macrophages. Macrophage numbers in aortic sinuses of CD11d-/- mice
      were reduced without affecting their apoptosis and proliferation. Adoptive
      transfer of fluorescently labeled wild-type and CD11d-/- monocytes into ApoE-/-
      mice demonstrated similar recruitment from circulation, but reduced accumulation
      of CD11d-/- macrophages within the aortas. Furthermore, CD11d expression was
      significantly upregulated on macrophages in atherosclerotic lesions and M1
      macrophages in vitro. Interestingly, expression of the related ligand-sharing
      integrin CD11b was not altered. This difference defines their distinct roles in
      the regulation of macrophage migration. CD11d-deficient M1 macrophages
      demonstrated improved migration in a three-dimensional fibrin matrix and during
      resolution of peritoneal inflammation, whereas migration of CD11b-/- M1
      macrophages was not affected. These results prove the contribution of high
      densities of CD11d to macrophage arrest during atherogenesis. Because high
      expression of CD11d was detected in several inflammation-dependent diseases, we
      suggest that CD11d/CD18 upregulation on proinflammatory macrophages may represent
      a common mechanism for macrophage retention at inflammatory sites, thereby
      promoting chronic inflammation and disease development.

PMID- 28500073
TI  - FcgammaRIIIa Signaling Modulates Endosomal TLR Responses in Human CD4+ T Cells.
AB  - Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc
      receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs
      and deliver them to endosomes, where they are recognized by nucleic acid-sensing
      TLRs (NA-TLRs). We show that in CD4+ T cells, NA-TLRs, TLR3, TLR8, and TLR9 are
      upregulated by FcgammaRIIIa-pSyk cosignaling and localize with FcgammaRIIIa on
      the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG
      oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in
      discriminating self versus viral nucleic acid. Hydroxychloroquine used for
      treating systemic lupus erythematosus and a Syk inhibitor blocked NA-TLR
      localization with FcgammaRIIIa. Engaging TLR9 with CpG oligonucleotide
      contributes to the development of IL17A+ and IL-21+ populations. RNA-sequencing
      analysis showed upregulation of proinflammatory cytokines, NF-kappaB signaling,
      and heat shock protein pathway RNA transcripts. These data suggest a role for
      FcgammaRIIIa-pSyk cosignaling in modulating NA-TLR responses in human CD4+ T
      cells by affecting the amounts and cellular distribution. These events are
      important for understanding of autoimmune pathology.

PMID- 28500075
TI  - Overexpression of Human CD55 and CD59 or Treatment with Human CD55 Protects
      against Renal Ischemia-Reperfusion Injury in Mice.
AB  - Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates
      renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of
      increasing CD55 and CD59 activity has not been examined. In this study, we
      investigated the impact of overexpression of human (h) CD55 +/- hCD59 or
      treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally
      nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm
      renal ischemia, and analyzed 24 h after reperfusion for renal function (serum
      creatinine and urea), complement deposition (C3b/c and C9), and infiltration of
      neutrophils and macrophages. Transgenic mice expressing hCD55 alone were
      protected against mild renal IRI, with reduced creatinine and urea levels
      compared with wild type littermates. However, the renal function of the hCD55
      mice was not preserved in the moderate IRI model, despite a reduction in C3b/c
      and C9 deposition and innate cell infiltration. Mice expressing both hCD55 and
      hCD59, on the other hand, were protected in the moderate IRI model, with
      significant reductions in all parameters measured. Wild type mice treated with
      rhCD55 immediately after reperfusion were also protected in the moderate IRI
      model. Thus, manipulation of CD55 activity to increase inhibition of the C3 and
      C5 convertases is protective against renal IRI, and the additional expression of
      hCD59, which regulates the terminal complement pathway, provides further
      protection. Therefore, anti-complement therapy using complement regulatory
      proteins may provide a potential clinical option for preventing tissue and organ
      damage in renal IRI.

PMID- 28500074
TI  - Disease-Specific Effects of Matrix and Growth Factors on Adhesion and Migration
      of Rheumatoid Synovial Fibroblasts.
AB  - In rheumatoid arthritis (RA), cartilage and bone matrix are degraded, and
      extracellular matrix (ECM) proteins, acting as cellular activators, are
      liberated. Similar to ECM proteins, matrix-bound chemokines, cytokines, and
      growth factors (GFs) influence functional properties of key cells in RA,
      especially synovial fibroblasts. The role of these molecules on attachment,
      migration, and proinflammatory and prodestructive activation of RASFs was
      analyzed. Adhesion/migration of RASFs were examined under GF-enriched (GF+) or 
      reduced (GF-) conditions with or without addition of matrix-associated GFs, TGF
      beta, and platelet-derived GF to GF- or culture supernatants. Fibroblast adhesion
      and alterations in proinflammatory/prodestructive properties (e.g., IL-6/matrix
      metalloproteinase 3-release) in response to matrix-associated molecules were
      compared. Effects of GF+, GF-, and other ECM components on human RASF-mediated
      cartilage invasion were examined in the SCID mouse model. RASF adhesion under GF-
      conditions was significantly lower compared with GF+ conditions (6.8- versus 8.3
      fold). This effect was specific for RA because control cells showed opposite
      effects (e.g., osteoarthritis synovial fibroblasts [SF]; GF- versus GF+: 10.7-
      versus 8-fold). Addition of TGF-beta to GF- increased RASF attachment (12.7-fold)
      compared with other matrices and components. RASF adhesion to GF+ matrix resulted
      in the strongest IL-6 and matrix metalloproteinase-3 release, and was even more
      pronounced compared with supplementation of single GFs. In vivo, GF- matrix
      decreased RASF-mediated cartilage invasion compared with GF+ matrix. ECM
      components and especially GFs when bound within ECM actively enhance RASF
      attraction and cartilage adhesion. This observation was specific for RASFs as a
      reverse behavior was observed for controls.

PMID- 28500076
TI  - Stat5 Is Required for CD103+ Dendritic Cell and Alveolar Macrophage Development
      and Protection from Lung Injury.
AB  - We tested the role of Stat5 in dendritic cell and alveolar macrophage (AM)
      homeostasis in the lung using CD11c-cre mediated deletion (Cre+5f/f). We show
      that Stat5 is required for CD103+ dendritic cell and AM development. We found
      that fetal monocyte maturation into AMs was impaired in Cre+5f/f mice, and we
      also confirmed impaired AM development of progenitor cells using mixed chimera
      experiments. In the absence of Stat5 signaling in AMs, mice developed alveolar
      proteinosis with altered lipid homeostasis. In addition, loss of Stat5 in CD11c+
      cells was associated with exaggerated LPS-induced inflammatory responses and
      vascular leak. In Cre+5f/f mice, there was loss of immune-dampening effects on
      epithelial cells, a key source of CCL2 that serves to recruit monocytes and
      macrophages. These findings demonstrate the critical importance of Stat5
      signaling in maintaining lung homeostasis, and underscore the importance of
      resident macrophages in moderating tissue damage and excess inflammation.

PMID- 28500077
TI  - Alternative Start Sites Downstream of Non-Sense Mutations Drive Antigen
      Presentation and Tolerance Induction to C-Terminal Epitopes.
AB  - CTL responses to the transgene product remain an active area of concern for the
      gene therapy field. A patient's underlying genetic mutation may influence the
      qualitative nature of these potentially destructive T cell responses. Individuals
      with a mutation that introduces a premature termination codon (PTC) that prevents
      synthesis of the full-length peptide are considered more likely to mount a
      transgene-specific T cell response because of a lack of immune tolerance to C
      terminal epitopes as a consequence of absent endogenous Ag presentation. In this
      article, we demonstrate that a human ornithine transcarbamylase gene containing
      various PTC-inducing non-sense mutations is able to generate and present epitopes
      downstream of the termination codon. Generation of these epitopes occurs
      primarily from alternative translation start sites downstream of the stop codon.
      Furthermore, we show that expression of these genes from adeno-associated virus
      vectors in C57BL/6 mice is able to induce peripheral tolerance to epitopes
      downstream of the PTC. These results suggest that, despite the lack of full
      length endogenous protein, patients with PTC-inducing non-sense mutations may
      still present T cell epitopes downstream of the premature termination site that
      may render the subject tolerant to wild-type transgene products.

PMID- 28500079
TI  - Exercise therapy for functional capacity in chronic diseases: an overview of meta
      analyses of randomised controlled trials.
AB  - OBJECTIVE: To summarise all meta-analyses of randomised controlled trials that
      have evaluated the effects of exercise therapy on functional capacity in patients
      with chronic diseases. DESIGN: Umbrella review of meta-analyses of randomised
      controlled trials. DATA SOURCES: We systematically searched the CENTRAL, CINAHL,
      DARE, Medline, OTSeeker, PEDro, SPORTDiscus, ProQuest Nursing & Allied Health
      Database, Web of Science, Scopus, OpenGrey and BMC Proceedings from database
      inception to 1 September 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We
      included meta-analyses that compared the effects of exercise therapy with no
      treatment or usual care in adults with non-communicable chronic diseases and
      included outcomes related to functional capacity. We excluded meta-analyses with
      less than 100 patients. RESULTS: Eighty-five meta-analyses with 22 different
      chronic diseases were included. The exercise interventions resulted in
      statistically significant (p<0.05) improvements for 126 of 146 (86%) functional
      capacity outcomes, compared with the control group. The standardised mean
      differences were small in 64 (44%), moderate in 54 (37%) and large in 28 (19%) of
      the 146 functional capacity outcomes. The results were similar for aerobic
      exercise, resistance training, and aerobic and resistance training combined.
      There were no significant differences in serious adverse effects between the
      intervention and control groups in any of the meta-analyses. CONCLUSION: Exercise
      therapy appears to be a safe way to improve functional capacity and reduce
      disability in individuals with chronic disease.

PMID- 28500080
TI  - Displaced middle-third clavicle fracture management in sport: still a challenge
      in 2018. Should you call the surgeon to speed return to play?

PMID- 28500078
TI  - A Time- and Compartment-Specific Activation of Lung Macrophages in Hypoxic
      Pulmonary Hypertension.
AB  - Studies in various animal models suggest an important role for pulmonary
      macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the
      molecular mechanisms characterizing the functional macrophage phenotype relative
      to time and pulmonary localization and compartmentalization remain largely
      unknown. In this study, we used a hypoxic murine model of PH in combination with
      FACS to quantify and isolate lung macrophages from two compartments over time and
      characterize their programing via RNA sequencing approaches. In response to
      hypoxia, we found an early increase in macrophage number that was restricted to
      the interstitial/perivascular compartment, without recruitment of macrophages to
      the alveolar compartment or changes in the number of resident alveolar
      macrophages. Principal component analysis demonstrated significant differences in
      overall gene expression between alveolar and interstitial macrophages (IMs) at
      baseline and after 4 and 14 d hypoxic exposure. Alveolar macrophages at both day
      4 and 14 and IMs at day 4 shared a conserved hypoxia program characterized by
      mitochondrial dysfunction, proinflammatory gene activation, and mTORC1 signaling,
      whereas IMs at day 14 demonstrated a unique anti-inflammatory/proreparative
      programming state. We conclude that the pathogenesis of vascular remodeling in
      hypoxic PH involves an early compartment-independent activation of lung
      macrophages toward a conserved hypoxia program, with the development of
      compartment-specific programs later in the course of the disease. Thus,
      harnessing time- and compartment-specific differences in lung macrophage
      polarization needs to be considered in the therapeutic targeting of macrophages
      in hypoxic PH and potentially other inflammatory lung diseases.

PMID- 28500081
TI  - Quadriceps strengthening with and without blood flow restriction in the treatment
      of patellofemoral pain: a double-blind randomised trial.
AB  - BACKGROUND: Quadriceps strengthening exercises are part of the treatment of
      patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee
      pain. Blood flow restriction (BFR) training may provide a low-load quadriceps
      strengthening method to treat PFP. METHODS: Seventy-nine participants were
      randomly allocated to a standardised quadriceps strengthening (standard) or low
      load BFR. Both groups performed 8 weeks of leg press and leg extension, the
      standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of
      1RM. Interventions were compared using repeated-measures analysis of variance for
      Kujala Patellofemoral Score, Visual Analogue Scale for 'worst pain' and 'pain
      with daily activity', isometric knee extensor torque (Newton metre) and
      quadriceps muscle thickness (cm). Subgroup analyses were performed on those
      participants with painful resisted knee extension at 60 degrees . RESULTS: Sixty
      nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR
      group had a 93% greater reduction in pain with activities of daily living
      (p=0.02) than the standard group. Participants with painful resisted knee
      extension (n=39) had greater increases in knee extensor torque with BFR than
      standard (p<0.01). No between-group differences were found for change in Kujala
      Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07)
      or quadriceps thickness (p=0.2). No difference was found between interventions at
      6 months. CONCLUSION: Compared with standard quadriceps strengthening, low load
      with BFR produced greater reduction in pain with daily living at 8 weeks in
      people with PFP. Improvements were similar between groups in worst pain and
      Kujala score. The subgroup with painful resisted knee extension had larger
      improvements in quadriceps strength from BFR. TRIAL REGISTRATION NUMBER:
      12614001164684.

PMID- 28500085
TI  - The most common vices of men can damage fertility and the health of the next
      generation.
AB  - Animal and human studies demonstrate that acquired paternal traits can impair
      both a male's fertility and the health of his offspring, including advanced age,
      smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity.
      Many of these factors lead to similar changes to neurological, behavioural,
      and/or metabolic functioning in offspring. The molecular mechanisms that both
      respond to the paternal environment and act to transmit traits to offspring are
      beginning to emerge. This review focuses on three vices of men (alcohol
      consumption, overweight/obesity, and tobacco smoking) that damage fertility and
      pose risks to offspring health. These vices are not only the three most prevalent
      but are also leading risk factors for death and disability adjusted life years
      (DALYs) worldwide. Moreover, given that these vices are predominantly self
      inflicted, interventions aimed at mitigating their consequences are readily
      identified.

PMID- 28500083
TI  - Hepatic thyroid signaling of heat-stressed late pregnant and early lactating
      cows.
AB  - During the transition between late gestation and early lactation, dairy cows
      experience severe metabolic stress due to the high energy and nutrient
      requirements of the fetus and the mammary gland. Additional thermal stress that
      occurs with rising temperatures during the ongoing climate change has further
      adverse implications on energy intake, metabolism and welfare. The thyroid
      hormone (TH)-mediated cellular signaling has a pivotal role in regulation of body
      temperature, energy intake and metabolic adaptation to heat. To distinguish
      between energy intake and heat stress-related effects, Holstein cows were first
      kept at thermoneutrality at 15 degrees C followed by exposure to heat stress (HS)
      at 28 degrees C or pair-feeding (PF) at 15 degrees C for 6 days, in late
      pregnancy and again in early lactation. Herein, we focused on hepatic metabolic
      changes associated with alterations in the hypothalamic-pituitary-thyroid axis in
      HS and PF animals. T3 and T4 levels dropped with HS or PF; however, in HS
      animals, this decline was more pronounced. Thyroid-stimulating hormone (TSH)
      levels remain unaffected, while plasma cholesterol concentrations were lower in
      HS than PF animals. Hepatic marker genes for TH action (THRA, DIO1 and PPARGC1)
      decreased after HS and were lower compared to PF cows but only post-partum.
      Proteomics data revealed reduced hepatic amino acid catabolism ante-partum and a
      shift toward activated beta-oxidation and gluconeogenesis but declined oxidative
      stress defense post-partum. Thus, liver metabolism of HS and PF cows adapts
      differently to diminished energy intake both ante-partum and post-partum, and a
      different TH sensitivity is involved in the regulation of catabolic processes.

PMID- 28500084
TI  - Bisphenol A promotes hepatic lipid deposition involving Kupffer cells M1
      polarization in male mice.
AB  - Bisphenol A (BPA), one of the most common environmental endocrine disruptors, is
      considered to promote hepatic lipid deposition. However, the mechanism has not
      been fully elucidated. The polarization of Kupffer cells (KCs) plays an important
      role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs),
      which contributes to dysregulated lipid metabolism. The purpose of this study is
      to investigate the role of KC polarization in BPA-induced hepatosteatosis in male
      mice. In this study, we examined hepatic lipid contents and quantified M1KC in
      BPA-treated CD1 mice, and further explored the interaction between KCs and
      hepatocytes using conditional HepG2 cell culture. BPA treatment significantly
      increased hepatic fat contents in CD1 mice, accompanied by increased number of
      pro-inflammatory M1KCs and enhanced secretion of inflammatory cytokines.
      Increased lipid contents were also observed in HepG2 cells treated with BPA.
      Interestingly, higher TG contents were observed in HepaG2 cells treated with
      conditional media from BPA-treated KCs, compared with those treated with BPA
      directly. Incubation of KCs with BPA promoted the polarization of KCs to pro
      inflammatory M1 dominant subtypes, which was blocked by estrogen antagonist
      ICI182780. Taken together, our results revealed that M1KCs polarization is
      involved in BPA-induced hepatic fat deposition, which is possibly associated with
      the estrogen receptor signaling pathway.

PMID- 28500086
TI  - Detection of pneumothoraces in patients with multiple blunt trauma: use and
      limitations of eFAST.
AB  - BACKGROUND: Extended focused assessment with sonography for trauma (eFAST) has
      been shown to have moderate sensitivity for detection of pneumothorax in trauma.
      Little is known about the location or size of missed pneumothoraces or clinical
      predictors of pneumothoraces in patients with false-negative eFAST. METHODS: This
      retrospective cross-sectional study includes all patients with multiple blunt
      trauma diagnosed with pneumothorax who underwent both eFAST and CT performed in
      the ED of a level 1 trauma centre in Switzerland between 1 June 2012 and 30
      September 2014. Sensitivity of eFAST for pneumothorax was determined using CT as
      the gold standard. Demographic and clinical characteristics of those who had a
      pneumothorax detected by eFAST and those who did not were compared using the Mann
      Whitney U or Pearson's chi2 tests. Univariate binary logistic regression models
      were used to identify predictors for pneumothoraces in patients with negative
      eFAST examination. RESULTS: The study included 109 patients. Overall sensitivity
      for pneumothorax on eFAST was 0.59 and 0.81 for pneumothoraces requiring
      treatment. Compared with those detected by eFAST, missed pneumothoraces were less
      likely to be ventral (30 (47.6%) vs 4 (9.3%), p <0.001) and more likely to be
      apical and basal (7 (11.1%) vs 15 (34.9%), p=0.003; 11 (17.5%) vs 18 (41.9%),
      p=0.008, respectively). The missed pneumothoraces were smaller than the detected
      pneumothoraces (left side: 30.7+/-17.4 vs 12.1+/-13.9 mm; right side: 30.2+/-10.1
      vs 6.9+/-10.2 mm, both p <0.001). No clinical variables were identified which
      predicted pneumothoraces in falsely negative eFAST. Among those pneumothoraces
      missed by eFAST, 30% required tube thoracostomy compared with 88.9% of those
      detected with eFAST. CONCLUSION: In our study, pneumothoraces missed by eFAST
      were smaller and in atypical locations compared with those detected by eFAST and
      needed thoracic drainage less often.

PMID- 28500088
TI  - Spotting the black swan: why emergency medicine is ahead of the curve.
AB  - "Black Swans", originally described as an economic theory, are unexpected events
      whose potential to occur only becomes apparent after they have happened. The
      concept is very relevant to the practice of Emergency Medicine and this article
      explores how black swans impact on emergency care and how staff unconsciously aim
      to mitigate against them.

PMID- 28500087
TI  - Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to
      safely reduce unnecessary hospital admissions: a pilot randomised controlled
      trial.
AB  - BACKGROUND: Observational studies suggest that the Manchester Acute Coronary
      Syndromes (MACS) decision rule can effectively 'rule out' and 'rule in' acute
      coronary syndromes (ACS) following a single blood test. In a pilot randomised
      controlled trial, we aimed to determine whether a large trial is feasible.
      METHODS: Patients presenting to two EDs with suspected cardiac chest pain were
      randomised to receive care guided by the MACS decision rule (intervention group)
      or standard care (controls). The primary efficacy outcome was a successful
      discharge from the ED, defined as a decision to discharge within 4 hours of
      arrival providing that the patient did not have a missed acute myocardial
      infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or
      coronary revascularisation) within 30 days. Feasibility outcomes included
      recruitment and attrition rates. RESULTS: In total, 138 patients were included
      between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to
      intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%)
      had incident MACE within 30 days. All 131 patients completed 30-day follow-up and
      were included in the final analysis with no missing data for the primary
      analyses. Compared with standard care, a significantly greater proportion of
      patients whose care was guided by the MACS rule were successfully discharged
      within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No
      patients in either group who were discharged within 4 hours had a diagnosis of
      AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention
      group). CONCLUSIONS: In this pilot trial, use of the MACS rule led to a
      significant increase in safe discharges from the ED but a larger, fully powered
      trial remains necessary. Our findings seem to support the feasibility of that
      trial. TRIAL REGISTRATION NUMBER: ISRCTN 86818215. RESEARCH ETHICS COMMITTEE
      REFERENCE: 13/NW/0081. UKCRN REGISTRATION ID: 14334.

PMID- 28500089
TI  - An exploration of patients' experiences of participation in a randomised
      controlled trial of the Manchester Acute Coronary Syndromes (MACS) decision rule.
AB  - BACKGROUND: As an important part of a pilot study to determine the feasibility of
      a large randomised controlled trial (RCT) comparing use of the Manchester Acute
      Coronary Syndromes (MACS) decision rule with standard care, we aimed to explore
      patient attitudes and potential barriers to participation in a trial of this
      nature. METHODS: We conducted a qualitative study nested within a pilot RCT
      comparing use of the MACS rule (which could enable some patients with chest pain
      to be discharged earlier) with standard care. Semi-structured interviews with
      consenting participants were conducted with reference to a bespoke topic guide.
      Interviews were audio recorded, transcribed verbatim and analysed using the
      Framework method with an inductive approach. RESULTS: The 10 interviewees
      expressed that participation in the trial was generally acceptable. All but one
      recommended participation to others. Participants who were in pain or anxious at
      the time of arrival reported that the initial invitation to participate in the
      trial was sometimes made too early. The approach was welcome, providing they had
      been given time to settle. Interviewees welcomed the opportunity that trial
      participation offered for them to play a more active role in their healthcare and
      to reduce unnecessary waiting time. Participants appeared to like the fact that
      participation in the trial might mean they could return home sooner and welcomed
      the provision of follow-up. Although several participants described being
      generally sceptical of medical research, they were amenable to participation in
      this trial. This appears to be because they agreed with the need for research in
      this field and perceived the intervention as non-invasive. CONCLUSIONS: Patients
      were positive about their participation in this RCT comparing the MACS rule with
      standard care. A number of areas for improving trial design were identified and
      should be considered in the planning of future large trials. TRIAL REGISTRATION:
      ISRCTN 86818215 RESEARCH ETHICS COMMITTEE REFERENCE: 13/NW/0081 UKCRN
      REGISTRATION ID: 14334.

PMID- 28500090
TI  - Effect of Facility IAC-Accreditation on CT Dose Awareness and Reduction.
AB  - PURPOSE: To assess characteristics of computed tomography (CT) facilities
      accredited by the Intersocietal Accreditation Commission (IAC) and evaluate the
      perceived effect of accreditation on CT radiation dose awareness and reduction.
      METHODS: IAC-accredited CT facilities were sent a survey in April 2016, which
      included 20 questions categorized into 5 groups: equipment and facility (7),
      patient safety/practice (5), protocols (2), dose reduction practice (3), and
      quality improvement (3). RESULTS: The response rate was 20.7% (N = 607). A
      majority of facilities (80%) reported that radiation dose was adjusted based on
      patient size. Before undergoing accreditation, 79% of facilities reported annual
      review of CT protocols and radiation exposure. Following accreditation, that
      number increased to 93%. A majority (77%) of respondents indicated that the
      accreditation process, along with the IAC Standards and Guidelines, increased
      awareness of radiation exposure; in addition, 36% indicated that radiation doses
      were lower after undertaking accreditation. DISCUSSION: This study demonstrated
      that most IAC-accredited facilities followed recommended radiation safety
      practices by adjusting radiation dose based on patient size, reviewing protocols
      annually, and participating in quality improvement activities that focus on
      patient radiation exposure. CONCLUSION: IAC-accredited facilities reported that
      the accreditation process had a positive effect on radiation dose awareness and
      reduced dose associated with CT examinations.

PMID- 28500091
TI  - Forensic Age Estimation Using the Medial Clavicular Epiphysis: A Study Review.
AB  - PURPOSE: To discuss current literature evaluating the medial clavicular epiphysis
      to assess an individual's age using various imaging modalities. METHODS: Four
      scholarly research databases were searched to find studies that examined living
      subjects. Several articles were included that used cadavers, and a textbook was
      used to detail the anatomy of the clavicle. Thirty-nine articles were analyzed.
      RESULTS: The literature indicated that several imaging modalities, including
      conventional radiography, computed tomography, magnetic resonance, and
      sonography, are being used to evaluate the medial clavicular epiphysis to
      estimate an individual's age in the forensic context. In addition to multiple
      modalities, researchers are using various staging classification systems, ethnic
      groups, and interpreter criteria to establish reference data. DISCUSSION: There
      is a need to determine the age of individuals involved in civil and criminal
      proceedings who do not have valid birth date documentation. The clavicle is the
      last bone in the human body to complete fusion. The clavicle begins to fuse in
      the early teens and completes medial epiphyseal fusion in the late 20s. Clavicle
      fusion spans the legally significant age range of 18 through 21. Multiple
      variables influence the final age estimation, including interpreters' experience,
      the individual's socioeconomic class or area of origin, and limitations within
      the imaging modalities. CONCLUSION: Computed tomography is the modality of choice
      for forensic age estimation using the medial clavicular epiphysis. Radiologic
      technologists should be cognizant of current forensic age estimation practices,
      and future research should continue to provide reference data to improve accuracy
      of age estimation in those individuals who lack documentation of their date of
      birth.

PMID- 28500092
TI  - Patient-centered Radiation Safety.
AB  - Some suggest radiation safety is evolving from a provider-centered process to a
      more patient-centered approach. This shift places additional responsibility on
      radiologic technologists to educate patients about the possible risks and
      benefits of medical radiation exposure so patients can be equal partners in their
      care. This article discusses the ethics of radiation protection and the
      development of the patient-centered approach, and the radiologic technologist's
      role in ensuring patient-centered radiation safety is addressed.

PMID- 28500094
TI  - Recent News.

PMID- 28500093
TI  - Vertebral Osteomyelitis and the Role of Imaging.
AB  - Vertebral osteomyelitis is a rare but serious infectious disease that causes
      inflammation and destruction of the spinal vertebrae. Prompt diagnosis and
      treatment are essential to avoid adverse outcomes. This article reviews risk
      factors for vertebral osteomyelitis, disease mechanisms, signs and symptoms, and
      diagnostic criteria. Medical imaging techniques for vertebral osteomyelitis are a
      main focus, and treatment, prognosis, and possible complications also are
      discussed. Finally, the special case of pediatric patients with vertebral
      osteomyelitis is presented.

PMID- 28500097
TI  - Data Analysis: Closing the Loop in Assessment.

PMID- 28500098
TI  - Student Reflections on Clinical: Lessons Learned.

PMID- 28500099
TI  - TeamSTEPPS: Addressing Imaging Procedure Appropriateness.

PMID- 28500100
TI  - EQUIP: Enhancing Quality Using the Inspection Program.

PMID- 28500102
TI  - Using Social Media and Hashtags to Engage Medical Imaging Students.

PMID- 28500101
TI  - Flamingo Stress View of the Pelvis.

PMID- 28500104
TI  - Technical Factors and Exposure Indicators.

PMID- 28500106
TI  - Medical 3-D Printing.
AB  - Three-dimensional printing is used in the manufacturing industry, medical and
      pharmaceutical research, drug production, clinical medicine, and dentistry, with
      implications for precision and personalized medicine. This technology is
      advancing the development of patient-specific prosthetics, stents, splints, and
      fixation devices and is changing medical education, treatment decision making,
      and surgical planning. Diagnostic imaging modalities play a fundamental role in
      the creation of 3-D printed models. Although most 3-D printed objects are rigid,
      flexible soft-tissue-like prosthetics also can be produced.

PMID- 28500107
TI  - Metastatic Breast Cancer.
AB  - Despite advances in breast cancer screening, diagnosis, and treatment, nearly 12%
      of patients with a diagnosis of breast cancer eventually develop metastatic
      disease, or breast cancer that has spread beyond the breast to other parts of the
      body. No cure for metastatic breast cancer yet exists, and it is associated with
      a poor prognosis: The 5-year survival rate is 26%. Nevertheless, many treatments
      can improve and extend the lives of patients with metastatic breast cancer. This
      article reviews the types of breast cancer and cancer staging systems. It also
      discusses the molecular subtypes of breast cancer, symptoms of metastatic breast
      cancer, and current treatments for the disease.

PMID- 28500108
TI  - Recent News.

PMID- 28500110
TI  - Bilateral brachial rhabdomyolysis caused by push-up exercise.

PMID- 28500109
TI  - Hemifacial spasm and neurovascular compression syndrome.

PMID- 28500111
TI  - Migration of a Nexplanon contraceptive implant to the pulmonary artery.
AB  - This is a case report of a 17-year-old woman who experienced distant
      intravascular migration of a radio-opaque Nexplanon contraceptive implant. She
      presented with an impalpable implant and this was located using CT in the left
      lower lobe pulmonary artery. Significant migration of a contraceptive implant is
      an uncommon risk. Using radio-opaque contraceptive implants such as Nexplanon
      increases the ability to locate them if migration occurs.

PMID- 28500112
TI  - Intra-abdominal inflammatory myofibroblastic tumour (IMT) mimicking gonadal mass
      in a male infant with undescended testes.
AB  - Inflammatory myofibroblastic tumour (IMT) is a rare benign neoplastic tumour,
      originally described as an inflammatory pseudotumor. Only a single case of IMT in
      the spermatic cord associated with undescended testes has been reported. We
      present a rare case of abdominal IMT in a male infant with undescended bilateral
      testes. The abdominopelvic mass was suspected to be a gonadal malignancy due to
      empty scrotal sac but proved to be otherwise on histopathology. Mass was
      completely resected and orchiopexy was performed for both undescended normal
      appearing testes. The patient developed a recurrent mass 2 months later involving
      the left spermatic cord and the left testicle. Radical surgery was performed with
      removal of the left testicle and spermatic cord. The patient was disease-free at
      1-year follow-up.

PMID- 28500113
TI  - Annular pancreas causing duodenal obstruction in an adult.

PMID- 28500114
TI  - Pseudoprogression in lung adenocarcinoma during treatment with nivolumab.

PMID- 28500115
TI  - Erroneously elevated glucose values due to maltose interference in mutant glucose
      dehydrogenase pyrroloquinolinequinone (mutant GDH-PQQ) based glucometer.
AB  - Currently available glucose test strip enzymes include glucose oxidase (GOD) and
      glucose dehydrogenase (GDH). In GDH-based glucometers, glucose oxidation can be
      catalysed by different cofactors: nicotinamide adenine dinucleotide (GDH-NAD),
      flavin adenine dinucleotide (GDH-FAD), pyrroloquinolinequinone (GDH-PQQ) and
      mutant GDH-PQQ. GOD-based and GDH-NAD-based glucometers are substrate-specific
      and do not react with sugars other than glucose. GDH-FAD reacts with xylose only
      in addition to glucose. GDH-PQQ is not glucose-specific; in addition to glucose,
      it reacts with different other sugars and produces falsely high values of
      capillary glucose in the presence of such substances. There are reports of
      several deaths associated with usage of GDH-PQQ-based test strips. A modified
      form of GDH-PQQ, the so-called mutant GDH-PQQ, is supposedly free from such
      interferences. In this article spuriously high glucose values due to maltose
      interference in a glucometer using the mutant GDH-PQQ chemistry are being
      reported.

PMID- 28500116
TI  - A 53-year-old man with dyspnoea, respiratory failure, consistent with infliximab
      induced acute interstitial pneumonitis after an accelerated induction dosing
      schedule.
AB  - A 53-year-old man with ulcerative colitis (UC) suffered fatal acute interstitial
      pneumonitis (AIP) post completing an accelerated infliximab induction course.
      This is the first case reported in this setting. A literature review found four
      similar cases of infliximab-induced interstitial lung disease in the setting of
      treating patients with UC using standard infliximab regimens had successful
      treatment of the subjects post infliximab discontinuation. Unfortunately, the
      patient we are presenting, who had an accelerated infliximab induction course,
      did not survive. Although a prior small trial along more recent new small studies
      continue to show a benefit in reducing the need for early colectomy with the
      accelerated infliximab induction regimen as salvage therapy, it should be used
      cautiously until more safety data are available. Further larger trials are
      required to investigate rare side effects that may be associated with this
      regimen such as rapidly progressive lung toxicity as seen in this patient.

PMID- 28500117
TI  - Intracranial hypotension causing pituitary enlargement.

PMID- 28500118
TI  - Isolated prostate cancer soft tissue recurrence 10 years after radical
      prostatectomy.
AB  - In advanced disease, prostate cancer is well known to invade locally as well as
      metastasise to distant locations. Metastases occur commonly in lymph nodes and
      bone but have also been known to involve certain visceral organs, particularly
      the lungs. Involvement of soft tissue by metastases is far less common,
      particularly in the context of cancer recurrence. We present the case of a male
      aged 68 years who presented with a rising prostate-specific antigen (PSA) 10
      years after radical prostatectomy (RP). The PSA increased despite salvage
      radiotherapy and was ultimately found to be caused by a PSA secreting prostate
      cancer soft tissue mass in the suprapubic region. Surgical resection of the mass
      caused a sharp decline in the PSA to negligible levels. This case highlights the
      need for ongoing surveillance post-RP and the potential for prostate cancer
      recurrence in the soft tissue that is refractory to routine salvage radiotherapy.

PMID- 28500119
TI  - Evaluating the pictorial warnings on tobacco products in Arabian Gulf countries
      against other international pictorial warnings.
AB  - BACKGROUND: Few assessments of pictorial warnings (PWs) on cigarette packs
      implemented in Gulf Cooperation Council (GCC) countries have been done. METHODS:
      This article includes two cross-sectional studies. In Study 1, convenience
      samples of adults from the Kingdom of Saudi Arabia (n=111) and USA (n=115)
      participated in a consumer survey to rate a total of nine PWs from the GCC,
      Australia and the UK. Outcome measures were affective responses to PWs and
      concerns about smoking. In Study 2, tobacco control experts (n=14) from multiple
      countries rated the same PWs on a potential efficacy scale and completed one open
      ended question about each. The PWs were altered to mask their country of origin.
      Analyses compared ranking on multiple outcomes and examined ratings by country of
      origin and by smoking status. RESULTS: In the consumer survey, participants from
      both countries rated the PWs from GCC lower than PWs from other countries on the
      two measures. The mixed-model analysis showed significant differences between the
      PWs from Australia and those from the GCC and between the PWs from the UK and
      those from the GCC (p<0.001) in the consumer and expert samples. The experts'
      comments about the PWs implemented in the GCC were negative overall and confirmed
      previously identified themes about effective PWs. CONCLUSION: This study shows
      PWs originating from the GCC had significantly lower ratings than those
      implemented in Australia and the UK. The GCC countries may need to re-evaluate
      the currently implemented PWs and update them periodically.

PMID- 28500120
TI  - The clinical conundrum of diagnosing and treating systemic sarcoidosis in a high
      TB burden area.
AB  - A 53-year-old woman from Southern India presented with weight loss, anorexia,
      fever and asthenia. Whole body positron emission tomography/computed tomography
      (PET-CT) showed fluorodeoxyglucose-avid mediastinal and abdominal lymphadenopathy
      with hepatic, splenic, parotid and lacrimal glandular inflammations. Endoscopic
      ultrasound-guided fine needle aspiration of subcarinal lymph node showed non
      caseating granulomas. Initial serum ACE level was elevated but with normal
      calcium. Despite the suspicion of sarcoidosis, a trial of antituberculosis
      therapy was started empirically due to similar presentations of disseminated
      tuberculosis (TB) in this high endemic area. The patient subsequently
      deteriorated and was admitted with symptomatic hypercalcaemia. Her subsequent ACE
      levels were very high, supportive of a diagnosis of systemic sarcoidosis. She was
      given steroid pulse therapy, and 5 months later had fully recovered. This case
      highlights the challenges faced by physicians in high TB-endemic areas when
      managing granulomatous diseases as they are concerned about missing TB, the
      difficulties in diagnosing sarcoidosis and the role of pulse steroid therapy.

PMID- 28500121
TI  - Angioleiomyoma of the upper lip.
AB  - This report describes a case of labial angioleiomyoma in a 52-year-old woman. The
      patient had noticed a slow-growing painless isolated mass in her upper lip for 6
      months. The mass was surgically excised, and pathological examination was
      consistent with angioleiomyoma. Surgical excision was curative, and there was no
      recurrence at 12-month follow-up.

PMID- 28500122
TI  - Navigating the benefits and burdens of life-saving treatment in severely
      decompensated cirrhosis: an illustrative, multisourced narrative.
AB  - Severely decompensated cirrhosis presents major challenges in terms of balancing
      the benefits and burdens of life-extending treatment. Using accounts and
      interviews with a patient, her mother, consultant hepatologists and a consultant
      intensivist, this article explores the decision making around a 43-year-old woman
      with alcoholic liver disease who died after 100 days in a hospital. Particular
      focus is given to decisions on escalation, recognition of futility, distress
      associated with therapy and how messages given during end-of-life discussions are
      processed. Without suggesting that the case is an example of ideal practice, the
      importance of frequent multidisciplinary discussion, clinical re-evaluation and
      continuity of care is emphasised.

PMID- 28500123
TI  - Enterococcus casseliflavus septicaemia associated with hepatobiliary infection in
      a 75-year-old man.
AB  - Enterococcus casseliflavus is a rare non-faecium, non-faecalis, vancomycin
      resistant enterococcus (VRE) that is responsible for up to 2% of all enterococcal
      infections. Septicaemia with this bacterium is usually seen in older patients
      with multiple comorbidities who have had several previous hospitalisations.
      Septicaemia with E. casseliflavus portends a poorer prognosis, and treatment
      usually involves administration of antienterococcal beta-lactams or anti-VRE
      medications such as linezolid or daptomycin. We present such a case of a 75-year
      old man who developed E. casseliflavus septicaemia of presumably hepatobiliary
      origin and responded well to treatment with intravenous beta-lactams.

PMID- 28500124
TI  - Unusual cause of mediastinal mass.

PMID- 28500125
TI  - Acute urinary retention and constipation precipitated by herpes zoster infection.
AB  - A 76-year-old man presented to the emergency department complaining of acute
      urinary retention (AUR) and severe constipation. His recent medical history
      included 4 days of treatment in the community for gluteal herpes zoster with
      famciclovir. A transurethral catheter was passed and the patient completed a full
      course of famciclovir with resolution of constipation. The patient's catheter was
      successfully removed 3 weeks after his presentation. We report on the clinical
      presentation and management of an unusual case of AUR and constipation caused by
      a zoster viral infection of the S2-S4 dermatome.

PMID- 28500126
TI  - Lemierre's syndrome; a rare cause of septic arthritis.
AB  - Lemierre's syndrome is a rare condition characterised by pharyngitis leading to
      septic thrombophlebitis of the internal jugular vein. Complications include
      pulmonary septic emboli, septic arthritis and disseminated intravascular
      coagulation. The authors present a case of a healthy woman aged 25 years with
      septic arthritis of the shoulder due to this unusual cause. This diagnosis was
      made via a combination of clinical, radiological and microbiological findings. It
      was successfully treated via surgical and antimicrobial interventions. The
      patient made a good recovery with minimal associated morbidity or loss of
      function. This case highlights the importance for awareness and high index of
      suspicion for rarer causes of septic arthritis in young healthy adults as early
      appropriate intervention maximises prognosis.

PMID- 28500127
TI  - The efficacy of hyperbaric oxygen therapy in the treatment of central retinal
      artery occlusion.
AB  - Central retinal artery occlusion (CRAO) is an ophthalmological emergency. Various
      treatment modalities have been tried, but none have shown to alter natural
      history of the disease. Hyperoxia can restore retinal oxygenation, and favourable
      results were obtained with hyperbaric oxygen therapy (HBOT). We report two
      patients with sudden visual loss due to CRAO treated with HBOT. Case 1: a 61-year
      old female, presented with CRAO in her left eye(OS). She was submitted to eight
      sessions of HBOT(2.4atmosphere absolute (ATA)). BCVA(Best corrected visual
      acuity) improved from counting fingers (CF) to 1.0 and fluorescein angiography
      (FA) showed a normalisation. Vascular study showed a value of 8.8% for HbA1c and
      ventricular extrasystoles. Case 2: a 69-year-old male presented with CRAO in his
      OS. Nine sessions of HBOT(2.4 ATA) were performed. Best corrected visual acuity
      (BCVA)improved from CF to 0.8 and the FA was normalised. Vascular study revealed
      an atheromatous carotid disease, and cardiac pathology. HBOT seems to be
      beneficial on the recovery of vision following CRAO.

PMID- 28500128
TI  - Retroperitoneal schwannoma: an unusual cause of abdominal distention.

PMID- 28500129
TI  - Terminal ileal lymphoma resembling abdominal abscess.

PMID- 28500130
TI  - A seizure-induced T8 burst fracture re-presenting as an acute abdomen.
AB  - A male aged 44 years presented to the emergency department with a 1-week history
      of intermittent right-sided abdominal pain radiating to the midline. Examination
      demonstrated a tender right upper quadrant with voluntary guarding and a low
      grade fever. One week previously, he had been admitted to hospital after an
      isolated, self-terminating seizure secondary to an deliberate venlafaxine
      overdose. His upper abdominal symptoms started immediately postseizure but at the
      time were attributed to musculoskeletal chest pain by the discharging team. Acute
      cholecystitis was suspected, but liver function tests, amylase and an erect chest
      radiograph were unremarkable.The abdominal pain responded well to morphine,
      permitting a thorough reassessment of the patient, which revealed midthoracic
      spine tenderness, previously undetected. Prior to this, the patient had not
      complained of any back pain. A CT scan confirmed a burst fracture of T8 requiring
      urgent transfer to the local spinal unit for posterior stabilisation.

PMID- 28500131
TI  - Cerebral venous sinus thrombosis during superselective intra-arterial infusion of
      cisplatin and concomitant radiotherapy for maxillary squamous cell carcinoma.

PMID- 28500132
TI  - The zinc finger E-box-binding homeobox 1 (Zeb1) promotes the conversion of mouse
      fibroblasts into functional neurons.
AB  - The zinc finger E-box-binding transcription factor Zeb1 plays a pivotal role in
      the epithelial-mesenchymal transition. Numerous studies have focused on the
      molecular mechanisms by which Zeb1 contributes to this process. However, the
      functions of Zeb1 beyond the epithelial-mesenchymal transition remain largely
      elusive. Using a transdifferentiation system to convert mouse embryonic
      fibroblasts (MEFs) into functional neurons via the neuronal transcription factors
      achaete-scute family bHLH (basic helix-loop-helix) transcription factor1 (Ascl1),
      POU class 3 homeobox 2 (POU3F2/Brn2), and neurogenin 2 (Neurog2, Ngn2) (ABN), we
      found that Zeb1 was up-regulated during the early stages of transdifferentiation.
      Knocking down Zeb1 dramatically attenuated the transdifferentiation efficiency,
      whereas Zeb1 overexpression obviously increased the efficiency of
      transdifferentiation from MEFs to neurons. Interestingly, Zeb1 improved the
      transdifferentiation efficiency induced by even a single transcription factor
      (e.g. Asc1 or Ngn2). Zeb1 also rapidly promoted the maturation of induced neuron
      cells to functional neurons and improved the formation of neuronal patterns and
      electrophysiological characteristics. Induced neuron cells could form functional
      synapse in vivo after transplantation. Genome-wide RNA arrays showed that Zeb1
      overexpression up-regulated the expression of neuron-specific genes and down
      regulated the expression of epithelial-specific genes during conversion. Taken
      together, our results reveal a new role for Zeb1 in the transdifferentiation of
      MEFs into neurons.

PMID- 28500133
TI  - The heme-regulatory motif of nuclear receptor Rev-erbbeta is a key mediator of
      heme and redox signaling in circadian rhythm maintenance and metabolism.
AB  - Rev-erbbeta is a heme-responsive transcription factor that regulates genes
      involved in circadian rhythm maintenance and metabolism, effectively bridging
      these critical cellular processes. Heme binding to Rev-erbbeta indirectly
      facilitates its interaction with the nuclear receptor co-repressor (NCoR1),
      resulting in repression of Rev-erbbeta target genes. Fe3+-heme binds in a 6
      coordinate complex with axial His and Cys ligands, the latter provided by a heme
      regulatory motif (HRM). Rev-erbbeta was thought to be a heme sensor based on a
      weak Kd value for the Rev-erbbeta.heme complex of 2 MUm determined with
      isothermal titration calorimetry. However, our group demonstrated with UV-visible
      difference titrations that the Kd value is in the low nanomolar range, and the
      Fe3+-heme off-rate is on the order of 10-6 s-1 making Rev-erbbeta ineffective as
      a sensor of Fe3+-heme. In this study, we dissected the kinetics of heme binding
      to Rev-erbbeta and provided a Kd for Fe3+-heme of ~0.1 nm Loss of the HRM axial
      thiolate via redox processes, including oxidation to a disulfide with a
      neighboring cysteine or dissociation upon reduction of Fe3+- to Fe2+-heme,
      decreased binding affinity by >20-fold. Furthermore, as measured in a co
      immunoprecipitation assay, substitution of the His or Cys heme ligands in Rev
      erbbeta was accompanied by a significant loss of NCoR1 binding. These results
      demonstrate the importance of the Rev-erbbeta HRM in regulating interactions with
      heme and NCoR1 and advance our understanding of how signaling through HRMs
      affects the major cellular processes of circadian rhythm maintenance and
      metabolism.

PMID- 28500134
TI  - The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono
      ubiquitination manner during osteogenic differentiation.
AB  - Poly-ubiquitination-mediated RUNX2 degradation is an important cause of age- and
      inflammation-related bone loss. NEDD4 family E3 ubiquitin protein ligases are
      thought to be the major regulators of RUNX2 poly-ubiquitination. However, we
      observed a mono-ubiquitination of RUNX2 that was catalyzed by WWP2, a member of
      the NEDD4 family of E3 ubiquitin ligases. WWP2 has been reported to catalyze the
      mono-ubiquitination of Goosecoid in chondrocytes, facilitating craniofacial
      skeleton development. In this study, we found that osteogenic differentiation of
      mesenchymal stem cells promoted WWP2 expression and nuclear accumulation.
      Knockdown of Wwp2 in mesenchymal stem cells and osteoblasts led to significant
      deficiencies of osteogenesis, including decreased mineral deposition and down
      regulation of osteogenic marker genes. Co-immunoprecipitation experiments showed
      the interaction of WWP2 with RUNX2 in vitro and in vivo Mono-ubiquitination by
      WWP2 leads to RUNX2 transactivation, as evidenced by the wild type of WWP2, but
      not its ubiquitin ligase-dead mutant, augmenting RUNX2-reponsive reporter
      activity. Moreover, deletion of WWP2-dependent mono-ubiquitination resulted in
      striking defects of RUNX2 osteoblastic activity. In addition, ectopic expression
      of the constitutively active type 1A bone morphogenetic protein receptor enhanced
      WWP2-dependent RUNX2 ubiquitination and transactivation, demonstrating a
      regulatory role of bone morphogenetic protein signaling in the WWP2-RUNX2 axis.
      Taken together, our results provide evidence that WWP2 serves as a positive
      regulator of osteogenesis by augmenting RUNX2 transactivation in a non
      proteolytic mono-ubiquitination manner.

PMID- 28500135
TI  - Dual Antiplatelet Therapy Continuation Beyond 1 Year After Drug-Eluting Stents: A
      Meta-Analysis of Randomized Trials.
AB  - BACKGROUND: The benefits and harms of dual antiplatelet therapy (DAPT)
      continuation beyond 1 year after drug-eluting stent implantation as compared with
      1-year DAPT remain controversial. METHODS AND RESULTS: We searched for randomized
      trials that compared longer than 1-year DAPT versus 1-year DAPT after drug
      eluting stenting. A meta-analysis was performed by using standard frequentist and
      random-effects Bayesian approaches. Four trials comprising 17 650 participants
      were included. Compared with 1-year DAPT, extended DAPT did not affect all-cause
      mortality (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.79-1.5; P=0.53)
      or cardiovascular mortality (OR, 1.03; 95% CI, 0.72-1.46; P=0.88). Extended DAPT
      was associated with a reduction in the risk of myocardial infarction (OR, 0.56;
      95% CI, 0.43-0.73; P<0.001), nonsignificant reductions of stent thrombosis (OR,
      0.46; 95% CI, 0.16-1.27; P=0.13), similar risk of stroke (OR, 0.91; 95% CI, 0.65
      1.26; P=0.56), and an increased risk of major bleeding (OR, 1.49; 95% CI, 1.06
      2.11; P=0.02). By using Bayesian meta-analysis, we found moderate evidence of a
      reduction of myocardial infarction (OR, 0.62; 95% credible intervals, 0.39-1.05)
      and weak evidence of an increase in major bleeding (OR, 1.66; 95% credible
      intervals, 0.89-3.09) associated with extended DAPT. CONCLUSIONS: In this meta
      analysis, extended DAPT beyond 1 year prevented myocardial infarctions and
      increased major bleedings, but the strength of evidence for these effects was not
      strong. DAPT continuation beyond 1 year showed no effects on mortality.

PMID- 28500136
TI  - Percutaneous Mechanical Circulatory Support Devices in Cardiogenic Shock.
AB  - Despite a high rate of early revascularization and use of intra-aortic balloon
      pump counterpulsation therapy, the prognosis of patients with cardiogenic shock
      has remained poor. In the hopes of improving outcomes, clinicians are
      increasingly turning to percutaneous left and right mechanical circulatory
      support devices. Until recently, the evidence base for these devices had
      consisted only of observational data, meta-analyses, and small feasibility
      trials. In this article, we describe the contemporary outcomes of patients with
      cardiogenic shock, the hemodynamics of cardiogenic shock, and hemodynamic effects
      of percutaneous mechanical circulatory support devices. We then use this
      discussion to provide clinicians with a useful framework for understanding when
      selecting between or while managing patients with a percutaneous mechanical
      circulatory support devices. We critically review the recently published data for
      and against the use of commercially available devices-the intra-aortic balloon
      pump counterpulsation, the Impella system, the TandemHeart, and venous-arterial
      extracorporeal membrane oxygenation-and highlight gaps in our understanding.
      Given such gaps, a consensus multidisciplinary approach that combines expertise
      from interventional cardiologists, heart failure specialists, cardiac surgeons,
      and cardiac anesthesiologists may help pair the right patient with the right
      device at the right time.

PMID- 28500137
TI  - Outcomes After Decompression of the Right Ventricle in Infants With Pulmonary
      Atresia With Intact Ventricular Septum Are Associated With Degree of Tricuspid
      Regurgitation: Results From the Congenital Catheterization Research
      Collaborative.
AB  - BACKGROUND: Outcomes after right ventricle (RV) decompression in infants with
      pulmonary atresia with intact ventricular septum vary widely. Descriptions of
      outcomes are limited to small single-center studies. METHODS AND RESULTS:
      Neonates undergoing RV decompression for pulmonary atresia with intact
      ventricular septum were included from 4 pediatric centers. Primary end point was
      reintervention post-RV decompression; secondary end points included circulation
      type at latest follow-up. Ninety-nine patients (71 with pulmonary atresia with
      intact ventricular septum and 28 with virtual atresia) underwent RV decompression
      at median 3 (25th-75th, 2-5) days of age. Seventy-one patients (72%) underwent at
      least 1 reintervention after decompression. Median duration of follow-up was 3
      years (range, 1-10). Freedom from reintervention was 51% at 1 month and 23% at 3
      years. In multivariable analysis, reintervention was associated with virtual
      atresia (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.28-091;
      P=0.027), smaller RV length (HR, 0.94; 95% CI, 0.89-0.99; P=0.027), and <=mild
      tricuspid regurgitation (TR; HR, 3.58; 95% CI, 2.04-6.30; P<0.001). Patients
      undergoing surgical shunt or ductal stent were less likely to have virtual
      atresia (HR, 0.36; 95% CI, 0.15-0.85; P=0.02) and more likely to have higher RV
      end-diastolic pressure (HR, 1.07; 95% CI, 1.00-1.15; P=0.057) and <=mild TR (HR,
      3.50; 95% CI, 1.75-7.0; P<0.001). Number of reinterventions was associated with
      <=mild TR (rate ratio, 1.87; 95% CI, 1.23-2.87; P=0.0037). Multivariable analysis
      indicated that <2-ventricle circulation status was associated with <=mild TR
      (odds ratio, 18.6; 95% CI, 5.3-65.2; P<0.001) and lower RV area (odds ratio,
      0.81; 95% CI, 0.72-0.91; P<0.001). CONCLUSIONS: Patients with pulmonary atresia
      with intact ventricular septum deemed suitable for RV decompression have a high
      reintervention burden although most achieve 2-ventricle circulation. TR <=mild at
      baseline is strongly associated with reintervention and <2-ventricle circulation
      at medium-term follow-up. Degree of baseline TR may be an important marker of
      long-term outcomes in this population.

PMID- 28500140
TI  - Therapeutic Management of Low-Gradient Aortic Stenosis: First Assess the State of
      the Schrodinger Cat Before Making a Decision.

PMID- 28500138
TI  - Legacy Effect of Coronary Perforation Complicating Percutaneous Coronary
      Intervention for Chronic Total Occlusive Disease: An Analysis of 26 807 Cases
      From the British Cardiovascular Intervention Society Database.
AB  - BACKGROUND: Coronary perforation (CP) during chronic total occlusion percutaneous
      coronary intervention for stable angina (CTO-PCI) is a rare but serious event.
      The evidence base is limited, and the long-term effects are unclear. Using a
      national PCI database, the incidence, predictors, and outcomes of CP during CTO
      PCI were defined. METHODS AND RESULTS: Data analyzed from the British
      Cardiovascular Intervention Society data set on all CTO-PCI procedures performed
      in England and Wales between 2006 and 2013. Multivariate logistic regressions and
      propensity scores were used to identify predictors of CP and its association with
      outcomes. A total of 376 CP were recorded from 26 807 CTO-PCI interventions
      (incidence of 1.40%) with an increase in frequency during the study period
      (P=0.012). Patient-related factors associated with an increased risk of CP were
      age and female sex. Procedural factors indicative of complex CTO intervention
      strongly related to an increased risk of CP with a close relationship between the
      number of complex strategies used and CP evident (P=0.008 for trend). Tamponade
      occurred in 16.6% and emergency surgery in 3.4% of cases. Adverse outcomes were
      frequent in those patients with perforation including bleeding, transfusion,
      myocardial infarction, and death. A legacy effect of perforation on mortality was
      evident, with an odds ratio for 12-month mortality of 1.60 for perforation
      survivors compared with matched nonperforation survivors without a CP (P<0.0001).
      CONCLUSIONS: Many of the factors associated with an increased risk of CP were
      related to CTO complexity. Perforation was associated with adverse outcomes, with
      a legacy effect on later mortality after CP also observed.

PMID- 28500139
TI  - High- Versus Low-Gradient Severe Aortic Stenosis: Demographics, Clinical
      Outcomes, and Effects of the Initial Aortic Valve Replacement Strategy on Long
      Term Prognosis.
AB  - BACKGROUND: There is considerable debate on the management of patients with low
      gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm2 with
      peak aortic jet velocity <=4.0 m/s, and mean aortic pressure gradient <=40 mm Hg.
      METHODS AND RESULTS: In the CURRENT AS registry (Contemporary Outcomes After
      Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there
      were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and
      conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS)
      and 1712 patients (initial AVR strategy: n=219, and conservative strategy:
      n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in
      LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison
      between the initial AVR and conservative groups, the propensity score-matched
      cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for
      each group) strata. The initial AVR strategy when compared with the conservative
      strategy was associated with markedly lower risk for a composite of aortic valve
      related death or heart failure hospitalization in both HG-AS and LG-AS strata
      (hazard ratio, 0.30; 95% confidence interval, 0.25-0.37; P<0.001 and hazard
      ratio, 0.46; 95% confidence interval, 0.32-0.67; P<0.001, respectively). Among
      1358 patients with LG-AS with preserved left ventricular ejection fraction, the
      initial AVR strategy was associated with a better outcome than the conservative
      strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23-0.59;
      P<0.001). CONCLUSIONS: The initial AVR strategy was associated with better
      outcomes than the conservative strategy in both HG-AS and LG-AS patients,
      although AVR was less frequently performed in LG-AS patients than in HG-AS
      patients. The favorable effect of initial AVR strategy was also seen in patients
      with LG-AS with preserved left ventricular ejection fraction. CLINICAL TRIAL
      REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier:
      UMIN000012140.

PMID- 28500145
TI  - Where are all the vet nurses?

PMID- 28500146
TI  - Reviewing Schedule 3: why now and what might the outcome be?
AB  - Liz Cox, chair of the RCVS VN Council and the Schedule 3 Working Party, explains
      more about the RCVS's review of Schedule 3.

PMID- 28500141
TI  - Chronic obstructive pulmonary disease in Scottish military veterans.
AB  - INTRODUCTION: Smoking is a major risk factor for chronic obstructive pulmonary
      disease (COPD). Serving military personnel have previously been shown to be more
      likely to smoke, and to smoke more heavily, than civilians, but there is no clear
      consensus as to whether in later life, as veterans, they experience a higher
      prevalence and mortality from COPD than do non-veterans. We examined the risk of
      COPD in Scottish veterans and assessed the impact of changes in military smoking.
      METHODS: Retrospective 30-year cohort study of 56 205 veterans born 1945-1985,
      and 172 741 people with no record of military service, matched for age, sex and
      area of residence, using Cox proportional hazard models to examine the
      association between veteran status, birth cohort, length of service and risk of
      COPD resulting in hospitalisation or death. RESULTS: There were 1966 (3.52%)
      cases of COPD meeting the definition in veterans, compared with 5434 (3.19%) in
      non-veterans. The difference was statistically significant (p=0.001) in the
      unadjusted model although it became non-significant after adjusting for
      deprivation. The highest risk was seen in the oldest (1945-1949) birth cohort and
      in veterans with the shortest service (Early Service Leavers). The risk was
      significantly reduced in veterans born from 1960, and in those with over 12
      years' service. CONCLUSIONS: Our findings are consistent with falling rates of
      military smoking since the 1960s, and with the reduction in smoking with longer
      service. The oldest veterans, and those with the shortest service, are least
      likely to have benefited from this, as reflected in their higher risk for COPD.

PMID- 28500148
TI  - One Health pioneer Lord Soulsby dies.

PMID- 28500149
TI  - Record numbers vote in RCVS elections.

PMID- 28500150
TI  - Team cow - BCVA marks 50th anniversary with charity push.

PMID- 28500154
TI  - Suspected adverse events, 2015.
AB  - The following article has been produced by the pharmacovigilance unit at the
      Veterinary Medicines Directorate (VMD) to provide a summary of some of the
      results from its surveillance work carried out in 2015Decrease in number of
      reports for food-producing speciesIncrease in number of pet animal reportsReports
      of dogs affected by medicines intended for large animals.

PMID- 28500155
TI  - Improving safety through changes to the practice culture.

PMID- 28500157
TI  - Possible effect of diet on stress and neuroendocrine parameters in dogs with
      behavioural disorders.

PMID- 28500158
TI  - Possible effect of diet on stress and neuroendocrine parameters in dogs with
      behavioural disorders.

PMID- 28500159
TI  - Business after Brexit.

PMID- 28500160
TI  - Summer meeting of the Veterinary Invertebrate Society.

PMID- 28500161
TI  - Helping feed bees and pollinators.

PMID- 28500169
TI  - Making an impact through research.
AB  - Julie Fitzpatrick grew up in rural Ayrshire, surrounded by dogs, cats, ponies and
      other animals, with aspirations of working in mixed practice. She now heads the
      Moredun Group in Edinburgh.

PMID- 28500170
TI  - JAK2 inhibitors for myeloproliferative neoplasms: what is next?
AB  - Since its approval in 2011, the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib
      has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its
      use in patients with hydroxyurea resistant or intolerant polycythemia vera (PV)
      is steadily increasing. Several other JAK2 inhibitors have entered clinical
      testing, but none have been approved and many have been discontinued.
      Importantly, the activity of these agents is not restricted to patients with JAK2
      V617F or exon 12 mutations. Although JAK2 inhibitors provide substantial clinical
      benefit, their disease-modifying activity is limited, and rational combinations
      with other targeted agents are needed, particularly in MF, in which survival is
      short. Many such combinations are being explored, as are other novel agents, some
      of which could successfully be combined with JAK2 inhibitors in the future. In
      addition, new JAK2 inhibitors with the potential for less myelosuppression
      continue to be investigated. Given the proven safety and efficacy of ruxolitinib,
      it is likely that ruxolitinib-based combinations will be a major way forward in
      drug development for MF. If approved, less myelosuppressive JAK2 inhibitors such
      as pacritinib or NS-018 could prove to be very useful additions to the
      therapeutic armamentarium in MF. In PV, inhibitors of histone deacetylases and
      human double minute 2 have activity, but their role, if any, in the future
      treatment algorithm is uncertain, given the availability of ruxolitinib and
      renewed interest in interferons. Ruxolitinib is in late-phase clinical trials in
      essential thrombocythemia, in which it could fill an important void for patients
      with troublesome symptoms.

PMID- 28500172
TI  - Induced Pluripotent Stem Cell-Derived Cardiomyocytes Provide In Vivo Biological
      Pacemaker Function.
AB  - BACKGROUND: Although multiple approaches have been used to create biological
      pacemakers in animal models, induced pluripotent stem cell-derived cardiomyocytes
      (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker
      function of iPSC-CMs in a canine model. METHODS AND RESULTS: Embryoid bodies were
      derived from human keratinocytes, their action potential characteristics
      determined, and their gene expression profiles and markers of differentiation
      identified. Atrioventricular blocked dogs were immunosuppressed, instrumented
      with VVI pacemakers, and injected subepicardially into the anterobasal left
      ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3
      2*106 cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4
      to 13 weeks, epinephrine (1 MUg kg-1 min-1) was infused, and the heart removed
      for histological or electrophysiological study. iPSC-CMs largely lost the markers
      of pluripotency, became positive for cardiac-specific markers. and manifested If
      dependent automaticity. Epicardial pacing of the injection site identified
      matching beats arising from that site by week 1 after implantation. By week 4,
      20% of beats were electronically paced, 60% to 80% of beats were matching, and
      mean and maximal biological pacemaker rates were 45 and 75 beats per minute.
      Maximum night and day rates of matching beats were 53+/-6.9 and 69+/-10.4 beats
      per minute, respectively, at 4 weeks. Epinephrine increased rate of matching
      beats from 35+/-4.3 to 65+/-4.0 beats per minute. Incubation of embryoid bodies
      with the vital dye, Dil, revealed the persistence of injected cells at the site
      of administration. CONCLUSIONS: iPSC-CMs can integrate into host myocardium and
      create a biological pacemaker. Although this is a promising development, rate and
      rhythm of the iPSC-CMs pacemakers remain to be optimized.

PMID- 28500173
TI  - TGF-beta1 (Transforming Growth Factor-beta1) Plays a Pivotal Role in Cardiac
      Myofibroblast Arrhythmogenicity.
AB  - BACKGROUND: TGF-beta1 (transforming growth factor-beta1) importantly contributes
      to cardiac fibrosis by controlling differentiation, migration, and collagen
      secretion of cardiac myofibroblasts. It is still elusive, however, to which
      extent TGF-beta1 alters the electrophysiological phenotype of myofibroblasts and
      cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte
      crosstalk observed in vitro. METHODS AND RESULTS: Patch-clamp recordings of
      cultured neonatal rat ventricular myofibroblasts revealed that TGF-beta1, applied
      for 24 to 48 hours at clinically relevant concentrations (<=2.5 ng/mL), causes
      substantial membrane depolarization concomitant with a several-fold increase of
      transmembrane currents. Transcriptome analysis revealed TGF-beta1-dependent
      changes in 29 of 63 ion channel/pump/connexin transcripts, indicating a
      pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not
      affecting cardiomyocyte membrane potentials and cardiomyocyte-cardiomyocyte gap
      junctional coupling, TGF-beta1 depolarized cardiomyocytes coupled to
      myofibroblasts by ~20 mV and increased gap junctional coupling between
      myofibroblasts and cardiomyocytes >5-fold as reflected by elevated connexin 43
      and consortin transcripts. TGF-beta1-dependent cardiomyocyte depolarization
      resulted from electrotonic crosstalk with myofibroblasts as demonstrated by
      immediate normalization of cardiomyocyte electrophysiology after targeted
      disruption of coupled myofibroblasts and by cessation of ectopic activity of
      cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional
      uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic
      activity, block of TGF-beta1 signaling completely abolished both arrhythmogenic
      conditions. CONCLUSIONS: TGF-beta1 profoundly alters the electrophysiological
      phenotype of cardiac myofibroblasts. Apart from possibly contributing to the
      control of cell function in general, the changes proved to be pivotal for
      proarrhythmic myofibroblast-cardiomyocyte crosstalk in vitro, which suggests that
      TGF-beta1 may play a potentially important role in arrhythmogenesis of the
      fibrotic heart.

PMID- 28500171
TI  - Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress
      tumor growth.
AB  - Platelet-derived microparticles (PMPs) are associated with enhancement of
      metastasis and poor cancer outcomes. Circulating PMPs transfer platelet microRNAs
      (miRNAs) to vascular cells. Solid tumor vasculature is highly permeable, allowing
      the possibility of PMP-tumor cell interaction. Here, we show that PMPs infiltrate
      solid tumors in humans and mice and transfer platelet-derived RNA, including
      miRNAs, to tumor cells in vivo and in vitro, resulting in tumor cell apoptosis.
      MiR-24 was a major species in this transfer. PMP transfusion inhibited growth of
      both lung and colon carcinoma ectopic tumors, whereas blockade of miR-24 in tumor
      cells accelerated tumor growth in vivo, and prevented tumor growth inhibition by
      PMPs. Conversely, Par4-deleted mice, which had reduced circulating microparticles
      (MPs), supported accelerated tumor growth which was halted by PMP transfusion.
      PMP targeting was associated with tumor cell apoptosis in vivo. We identified
      direct RNA targets of platelet-derived miR-24 in tumor cells, which included
      mitochondrial mt-Nd2, and Snora75, a noncoding small nucleolar RNA. These RNAs
      were suppressed in PMP-treated tumor cells, resulting in mitochondrial
      dysfunction and growth inhibition, in an miR-24-dependent manner. Thus, platelet
      derived miRNAs transfer in vivo to tumor cells in solid tumors via infiltrating
      MPs, regulate tumor cell gene expression, and modulate tumor progression. These
      findings provide novel insight into mechanisms of horizontal RNA transfer and add
      multiple layers to the regulatory roles of miRNAs and PMPs in tumor progression.
      Plasma MP-mediated transfer of regulatory RNAs and modulation of gene expression
      may be a common feature with important outcomes in contexts of enhanced vascular
      permeability.

PMID- 28500174
TI  - Effect of Digoxin Use Among Medicaid Enrollees With Atrial Fibrillation.
AB  - BACKGROUND: Recently published analysis of contemporary atrial fibrillation (AF)
      cohorts showed an association between digoxin and increased mortality and
      hospitalizations; however, other studies have demonstrated conflicting results.
      Many AF cohort studies did not or were unable to examine racial differences. Our
      goal was to examine risk factors for hospitalizations and mortality with digoxin
      use in a diverse real-world AF patient population and evaluate racial
      differences. METHODS AND RESULTS: We performed a retrospective cohort analysis of
      claims data for Medicaid beneficiaries, aged 18 to 64 years, with incident
      diagnosis of AF in 2008 with follow-up until December 31, 2009. We created Kaplan
      Meier curves and constructed multivariable Cox proportional hazard models for
      mortality and hospitalization. We identified 11 297 patients with an incident
      diagnosis of AF in 2008, of those, 1401 (12.4%) were on digoxin. Kaplan-Meier
      analysis demonstrated an increased risk of hospitalization with digoxin use
      overall and within race and heart failure groups. In adjusted models, digoxin was
      associated with an increased risk of hospitalization (adjusted hazard ratio,
      1.54; 95% confidence interval, 1.39-1.70) and mortality (adjusted hazard ratio,
      1.50; 95% confidence interval, 1.05-2.13). Overall, blacks had a higher risk of
      hospitalization but similar mortality when compared with whites regardless of
      digoxin use. We found no significant interaction between race and digoxin use for
      mortality (P=0.4437) and hospitalization (P=0.7122). CONCLUSIONS: Our study
      demonstrates an overall increased risk of hospitalizations and mortality with
      digoxin use but no racial/ethnic differences in outcomes were observed. Further
      studies including minority populations are needed to critically evaluate these
      associations.

PMID- 28500175
TI  - Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial
      Fibrillation.
AB  - BACKGROUND: Recent studies have demonstrated conflicting mechanisms underlying
      atrial fibrillation (AF), with the spatial resolution of data often cited as a
      potential reason for the disagreement. The purpose of this study was to
      investigate whether the variation in spatial resolution of mapping may lead to
      misinterpretation of the underlying mechanism in persistent AF. METHODS AND
      RESULTS: Simulations of rotors and focal sources were performed to estimate the
      minimum number of recording points required to correctly identify the underlying
      AF mechanism. The effects of different data types (action potentials and unipolar
      or bipolar electrograms) and rotor stability on resolution requirements were
      investigated. We also determined the ability of clinically used endocardial
      catheters to identify AF mechanisms using clinically recorded and simulated data.
      The spatial resolution required for correct identification of rotors and focal
      sources is a linear function of spatial wavelength (the distance between
      wavefronts) of the arrhythmia. Rotor localization errors are larger for
      electrogram data than for action potential data. Stationary rotors are more
      reliably identified compared with meandering trajectories, for any given spatial
      resolution. All clinical high-resolution multipolar catheters are of sufficient
      resolution to accurately detect and track rotors when placed over the rotor core
      although the low-resolution basket catheter is prone to false detections and may
      incorrectly identify rotors that are not present. CONCLUSIONS: The spatial
      resolution of AF data can significantly affect the interpretation of the
      underlying AF mechanism. Therefore, the interpretation of human AF data must be
      taken in the context of the spatial resolution of the recordings.

PMID- 28500176
TI  - Mitral-Aortic Flow Reversal in Cardiac Resynchronization Therapy: Coupling With
      Ejection and Impact of Variations in Atrioventricular Delay.
AB  - BACKGROUND: Flow entering the left ventricle is reversed toward the outflow tract
      through rotating reversal flow around the mitral valve. This was thought to
      facilitate early ejection, but had not been proved to date. We hypothesized that
      perfect coupling between reversal and ejection flow would occur at optimal
      atrioventricular delay (AVD), contributing to its hemodynamic superiority, and
      evaluated its applicability for AVD optimization. METHODS AND RESULTS: Forty
      consecutive patients with cardiac resynchronization therapy underwent
      intracardiac flow analysis and AVD optimization. Reversal and ejection flow
      curves were studied. The presence and duration of reversal-ejection discontinuity
      were assessed for all programmed AVD. Reproducibility of each optimization method
      was evaluated through interobserver variability. Discontinuity between reversal
      and ejection flow was observed in all patients with longer than optimal AVD,
      increasing linearly with excess duration in AVD (linear R2=0.976, P<0.001).
      Longer discontinuities implied progressive decreases in pre-ejection flow
      velocity in the left ventricular outflow tract, with consequent loss of flow
      momentum. The equation optimal AVD=programmed AVD-[1.2(discontinuity duration)]+4
      accurately predicted optimal AVD. Short AVD systematically compromised reversal
      flow because of premature ejection. Agreement over optimal AVD was superior when
      assessed by flow reversal method (intraclass correlation coefficient =0.931;
      P<0.001) over both iterative and aortic velocity-time integral methods.
      CONCLUSIONS: Perfect coupling between mitral-aortic flow reversal and ejection
      flow in the left ventricle occurs at optimal AVD. As a result, full blood
      momentum in the outflow tract is used to facilitate early ejection. This can be
      measured and provides a new method for AVD optimization.

PMID- 28500177
TI  - Efficacy of an Anatomical Approach in Radiofrequency Catheter Ablation of
      Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Outflow
      Tract.
AB  - BACKGROUND: When anatomic obstacles preclude radiofrequency catheter ablation of
      idiopathic ventricular arrhythmias (VAs) originating from the left ventricular
      outflow tract (LVOT), an alternative approach from the anatomically opposite side
      (endocardial versus epicardial or above versus below the aortic valve) may be
      considered (anatomic ablation). The purpose of this study was to investigate the
      efficacy of an anatomic ablation in idiopathic LVOT VAs. METHODS AND RESULTS: We
      studied 229 consecutive patients with idiopathic LVOT VAs. Radiofrequency
      ablation from the first suitable site was successful in 190 patients, and in the
      remaining 39 patients, it was unsuccessful or had to be abandoned because of
      anatomic obstacles. In 22 of these 39 patients, an anatomic ablation was
      successful, and the VA origins were located in the intramural LVOT in 17
      patients, basal left ventricular summit in 4, and LVOT septum near the His bundle
      in 1. The anatomic ablation was highly successful for idiopathic VAs originating
      from the intramural LVOT (>75%) and lateral LVOT, whereas it was unlikely to be
      successful for idiopathic VAs originating from the basal left ventricular summit
      (25%) and sepal LVOT. CONCLUSIONS: When a standard catheter ablation targeting
      the best electrophysiological measure of idiopathic LVOT VAs was unsuccessful or
      had to be abandoned because of anatomic obstacles, an anatomic ablation was
      moderately successful. These idiopathic LVOT VAs with a successful anatomic
      ablation commonly arose from the intramural LVOT among the left coronary cusp,
      aortomitral continuity, and epicardium, occasionally the basal left ventricular
      summit, and rarely the LVOT septum near the His bundle.

PMID- 28500180
TI  - Induced Pluripotent Stem Cell-Based Treatment of Acquired Heart Block: The Battle
      for Tomorrow Has Begun!

PMID- 28500179
TI  - Is TGF-beta1 (Transforming Growth Factor-beta1) an Enabler of Myofibroblast
      Cardiomyocyte Cross Talk?

PMID- 28500178
TI  - Electrical Substrate Elimination in 135 Consecutive Patients With Brugada
      Syndrome.
AB  - BACKGROUND: There is emerging evidence that localization and elimination of
      abnormal electric activity in the epicardial right ventricular outflow tract may
      be beneficial in patients with Brugada syndrome. METHODS AND RESULTS: A total of
      135 symptomatic Brugada syndrome patients having implantable cardiac
      defibrillator were enrolled: 63 (group 1) having documented ventricular
      tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related
      symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at
      the time of symptoms. About 27 patients of group 1 experienced multiple
      implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three
      dimensional maps before and after ajmaline determined the arrhythmogenic
      electrophysiological substrate (AES) as characterized by prolonged fragmented
      ventricular potentials. Primary end point was identification and elimination of
      AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive
      areas of AES were found in the right ventricle epicardium, which were wider in
      group 1 (P=0.007). AES increased after ajmaline in both groups (P<0.001) and was
      larger in men (P=0.008). The increase of type-1 ST-segment elevation correlated
      with AES expansion (r=0.682, P<0.001). Radiofrequency ablation eliminated AES
      leading to ECG normalization and VT/VF noninducibility in all patients. During a
      median follow-up of 10 months, the ECG remained normal even after ajmaline in all
      except 2 patients who underwent a repeated effective procedure for recurrent VF.
      CONCLUSIONS: In Brugada syndrome, AES is commonly located in the right ventricle
      epicardium and ajmaline exposes its extent and distribution, which is correlated
      with the degree of coved ST-elevation. AES elimination by radiofrequency ablation
      results in ECG normalization and VT/VF noninducibility. Substrate-based ablation
      is effective in potentially eliminating the arrhythmic consequences of this
      genetic disease. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov.
      Unique identifier: NCT02641431.

PMID- 28500181
TI  - Nucleolar caspase-2: Protecting us from DNA damage.
AB  - Caspase-2 triggers apoptosis, but how it is activated by different stimuli is
      unclear. In this issue, Ando et al. (2017. J. Cell Biol.
      https://doi.org/10.1083/jcb.201608095) delineate two pathways of caspase-2
      activation and show that, in response to DNA damage, caspase-2 forms a complex
      with the PIDDosome and NPM1 within the nucleolus.

PMID- 28500182
TI  - UPR transducer BBF2H7 allows export of type II collagen in a cargo- and
      developmental stage-specific manner.
AB  - The unfolded protein response (UPR) handles unfolded/misfolded proteins
      accumulated in the endoplasmic reticulum (ER). However, it is unclear how
      vertebrates correctly use the total of ten UPR transducers. We have found that ER
      stress occurs physiologically during early embryonic development in medaka fish
      and that the smooth alignment of notochord cells requires ATF6 as a UPR
      transducer, which induces ER chaperones for folding of type VIII (short-chain)
      collagen. After secretion of hedgehog for tissue patterning, notochord cells
      differentiate into sheath cells, which synthesize type II collagen. In this
      study, we show that this vacuolization step requires both ATF6 and BBF2H7 as UPR
      transducers and that BBF2H7 regulates a complete set of genes (Sec23/24/13/31,
      Tango1, Sedlin, and KLHL12) essential for the enlargement of COPII vesicles to
      accommodate long-chain collagen for export, leading to the formation of the
      perinotochordal basement membrane. Thus, the most appropriate UPR transducer is
      activated to cope with the differing physiological ER stresses of different
      content types depending on developmental stage.

PMID- 28500184
TI  - Does not compute.

PMID- 28500186
TI  - Medication access via hospital admission.

PMID- 28500188
TI  - End-of-life care.

PMID- 28500183
TI  - The chromokinesin Klp3a and microtubules facilitate acentric chromosome
      segregation.
AB  - Although poleward segregation of acentric chromosomes is well documented, the
      underlying mechanisms remain poorly understood. Here, we demonstrate that
      microtubules play a key role in poleward movement of acentric chromosome
      fragments generated in Drosophila melanogaster neuroblasts. Acentrics segregate
      with either telomeres leading or lagging in equal frequency and are
      preferentially associated with peripheral bundled microtubules. In addition,
      laser ablation studies demonstrate that segregating acentrics are mechanically
      associated with microtubules. Finally, we show that successful acentric
      segregation requires the chromokinesin Klp3a. Reduced Klp3a function results in
      disorganized interpolar microtubules and shortened spindles. Normally, acentric
      poleward segregation occurs at the periphery of the spindle in association with
      interpolar microtubules. In klp3a mutants, acentrics fail to localize and
      segregate along the peripheral interpolar microtubules and are abnormally
      positioned in the spindle interior. These studies demonstrate an unsuspected role
      for interpolar microtubules in driving acentric segregation.

PMID- 28500189
TI  - Choice is led by values.

PMID- 28500190
TI  - Response.

PMID- 28500191
TI  - Family physicians' role in hidradenitis suppurativa management.

PMID- 28500193
TI  - Viral myositis in children.
AB  - Question I recently evaluated a child in my clinic after an emergency department
      visit where she presented having woken up that morning refusing to walk and was
      crawling around the house. The parents reported she was getting over a cold, and
      I recall similar cases of myositis during the H1N1 influenza epidemic a few years
      ago. What are the key features of myositis that I should recognize? Which
      investigations are needed to confirm the diagnosis and how should affected
      patients be managed? Answer Benign acute childhood myositis is a mild and self
      limited sudden onset of lower extremity pain during or following recovery from a
      viral illness. Presentation can include tiptoe gait or refusal to walk, secondary
      to symmetric bilateral lower extremity pain that resolves quickly, usually within
      3 days. In general, no investigation is needed except in severe cases for which
      screening bloodwork and a urine myoglobin test can confirm the diagnosis and rule
      out complications. Myoglobinuria and highly elevated creatine phosphokinase
      levels are rare but should be a consideration for admission to hospital.
      Prognosis is excellent and management might include rest and analgesia.

PMID- 28500192
TI  - Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline.
AB  - OBJECTIVE: To develop an evidence-based guideline to help clinicians make
      decisions about when and how to safely taper or stop proton pump inhibitors
      (PPIs); to focus on the highest level of evidence available and seek input from
      primary care professionals in the guideline development, review, and endorsement
      processes. METHODS: Five health professionals (1 family physician, 3 pharmacists,
      and 1 gastroenterologist) and 5 nonvoting members comprised the overall team;
      members disclosed conflicts of interest. The guideline process included the GRADE
      (Grading of Recommendations Assessment, Development and Evaluation) approach,
      with a detailed evidence review in in-person, telephone, and online meetings.
      Uniquely, the guideline development process included a systematic review of PPI
      deprescribing trials and examination of reviews of the harm of continued PPI use.
      Narrative syntheses of patient preferences and resource-implication literature
      informed recommendations. The team refined guideline content and recommendation
      wording through consensus and synthesized clinical considerations to address
      common front-line clinician questions. The draft guideline was distributed to
      clinicians and then to health care professional associations for review and
      revisions made at each stage. A decision-support algorithm was developed in
      conjunction with the guideline. RECOMMENDATIONS: This guideline recommends
      deprescribing PPIs (reducing dose, stopping, or using "on-demand" dosing) in
      adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or
      mild to moderate gastroesophageal reflux disease or esophagitis, and whose
      symptoms are resolved. The recommendations do not apply to those who have or have
      had Barrett esophagus, severe esophagitis grade C or D, or documented history of
      bleeding gastrointestinal ulcers. CONCLUSION: This guideline provides practical
      recommendations for making decisions about when and how to reduce the dose of or
      stop PPIs. Recommendations are meant to assist with, not dictate, decision making
      in conjunction with patients.

PMID- 28500195
TI  - Glucagonlike peptide 1 analogs in diabetes care.

PMID- 28500194
TI  - Million dollar ride: Crime committed during involuntary scopolamine intoxication.

PMID- 28500196
TI  - Choosing Wisely Canada.

PMID- 28500197
TI  - Establishing and growing the scope of practice of physician assistants.

PMID- 28500198
TI  - Triple antithrombotic therapy for atrial fibrillation and coronary stents.

PMID- 28500200
TI  - Hope.

PMID- 28500199
TI  - Data quality in electronic medical records in Manitoba: Do problem lists reflect
      chronic disease as defined by prescriptions?
AB  - OBJECTIVE: To determine if the problem list (health conditions) in primary care
      electronic medical records (EMRs) accurately reflects the conditions for which
      chronic medications are prescribed in the EMR. DESIGN: A retrospective analysis
      of EMR data. SETTING: Eighteen primary care clinics across rural and urban
      Manitoba using the Accuro EMR. PARTICIPANTS: Data from the EMRs of active
      patients seen in an 18-month period (December 18, 2011, to June 18, 2013, or
      December 3, 2012, to June 3, 2014) were used. MAIN OUTCOME MEASURES: The
      likelihood of documentation in the EMR problem list of those specific chronic
      diseases for which drug prescriptions were documented in the EMR. Regression
      modeling was performed to determine the effect of clinic patient load and
      remuneration type on the completeness of EMR problem lists. RESULTS: Overall
      problem-list completeness was low but was highest for diabetes and lowest for
      insomnia. Fee-for-service clinics generally had lower problem-list completeness
      than salaried clinics did for all prescription medications examined. Panel size
      did not affect problem-list completeness rates. CONCLUSION: The low EMR problem
      list completeness suggests that this field is not reliable for use in quality
      improvement initiatives or research until higher reliability has been
      demonstrated. Further research is recommended to explore the reasons for the poor
      quality and to support improvement efforts.

PMID- 28500201
TI  - Thinking like a rebel: Listening to patients, partnering with disease, finding
      the inspiration in suffering.

PMID- 28500202
TI  - Osteoporosis management in residential care: How internal and family medicine
      resident physicians translate evidence into practice.

PMID- 28500203
TI  - Indigenous health: time for action.

PMID- 28500206
TI  - Comprehensiveness revisited: Family Medicine Responsibility Profile.

PMID- 28500210
TI  - First-line medications for alcohol use disorders among public drug plan
      beneficiaries in Ontario.
AB  - OBJECTIVE: To examine use of first-line alcohol use disorder (AUD) medications
      (naltrexone and acamprosate) among public drug plan beneficiaries in the year
      following an AUD diagnosis. DESIGN: Retrospective population-based cohort study.
      SETTING: Ontario. PARTICIPANTS: Individuals eligible for public drug plan
      benefits who had an AUD diagnosis at a hospital visit between April 1, 2011, and
      March 31, 2012. MAIN OUTCOME MEASURES: Number of AUD medications dispensed to
      public drug plan beneficiaries who had a recent hospital visit with an AUD
      diagnosis, and number of prescriptions dispensed per person. RESULTS: A total of
      10 394 Ontarians between 18 and 65 years of age were identified who had a
      hospital visit with an AUD diagnosis and were eligible for public drug plan
      benefits. The rate of AUD medications dispensed in the subsequent year was 3.56
      per 1000 population (95% CI 2.51 to 4.91; n = 37). This rate did not differ
      significantly by sex (P = .83). CONCLUSION: Very few public drug plan
      beneficiaries are dispensed first-line AUD medications in the year following an
      AUD diagnosis.

PMID- 28500211
TI  - Computer use in primary care practices in Canada.
AB  - OBJECTIVE: To examine the use of computers in primary care practices. DESIGN: The
      international Quality and Cost of Primary Care study was conducted in Canada in
      2013 and 2014 using a descriptive cross-sectional survey method to collect data
      from practices across Canada. Participating practices filled out several surveys,
      one of them being the Family Physician Survey, from which this study collected
      its data. SETTING: All 10 Canadian provinces. PARTICIPANTS: A total of 788 family
      physicians. MAIN OUTCOME MEASURES: A computer use scale measured the extent to
      which family physicians integrated computers into their practices, with higher
      scores indicating a greater integration of computer use in practice. Analyses
      included t tests and 2 tests comparing new and traditional models of primary care
      on measures of computer use and electronic health record (EHR) use, as well as
      descriptive statistics. RESULTS: Nearly all (97.5%) physicians reported using a
      computer in their practices, with moderately high computer use scale scores (mean
      [SD] score of 5.97 [2.96] out of 9), and many (65.7%) reported using EHRs.
      Physicians with practices operating under new models of primary care reported
      incorporating computers into their practices to a greater extent (mean [SD] score
      of 6.55 [2.64]) than physicians operating under traditional models did (mean [SD]
      score of 5.33 [3.15]; t726.60 = 5.84; P < .001; Cohen d = 0.42, 95% CI 0.808 to
      1.627) and were more likely to report using EHRs (73.8% vs 56.7%; [Formula: see
      text]; P < .001; odds ratio = 2.15). Overall, there was a statistically
      significant variability in computer use across provinces. CONCLUSION: Most family
      physicians in Canada have incorporated computers into their practices for
      administrative and scholarly activities; however, EHRs have not been adopted
      consistently across the country. Physicians with practices operating under the
      new, more collaborative models of primary care use computers more comprehensively
      and are more likely to use EHRs than those in practices operating under
      traditional models of primary care.

PMID- 28500214
TI  - Efficacy of the Telemedical Lifestyle intervention Program TeLiPro in Advanced
      Stages of Type 2 Diabetes: A Randomized Controlled Trial.
AB  - OBJECTIVE: Lifestyle interventions are the foundation of treatment in newly
      diagnosed type 2 diabetes. However, their therapeutic potential in advanced
      disease stages is unknown. We evaluated the efficacy of the Telemedical Lifestyle
      intervention Program (TeLiPro) in improving metabolic control in advanced-stage
      type 2 diabetes. RESEARCH DESIGN AND METHODS: In this single-blind, active
      comparator, intervention study, patients with type 2 diabetes (with glycated
      hemoglobin [HbA1c] >=7.5% [58.5 mmol/mol]), and BMI >=27 kg/m2 and on >=2
      antidiabetes medications) were recruited in Germany and randomized 1:1 using an
      electronically generated random list and sealed envelopes into two parallel
      groups. The data analyst was blinded after assignment. The control group (n =
      100) got weighing scales and step counters and remained in routine care. The
      TeLiPro group (n = 102) additionally received telemedical coaching including
      medical-mental motivation, a formula diet, and self-monitored blood glucose for
      12 weeks. The primary end point was the estimated treatment difference in HbA1c
      reduction after 12 weeks. All available values per patient (n = 202) were
      analyzed. Analyses were also performed at 26 and 52 weeks of follow-up. RESULTS:
      HbA1c reduction was significantly higher in the TeLiPro group (mean +/- SD -1.1
      +/- 1.2% vs. -0.2 +/- 0.8%; P < 0.0001). The estimated treatment difference in
      the fully adjusted model was 0.8% (95% CI 1.1; 0.5) (P < 0.0001). Treatment
      superiority of TeLiPro was maintained during follow-up (week 26: 0.6% [95% CI
      1.0; 0.3], P = 0.0001; week 52: 0.6% [0.9; 0.2], P < 0.001). The same applies for
      secondary outcomes: weight (TeLiPro -6.2 +/- 4.6 kg vs. control -1.0 +/- 3.4 kg),
      BMI (-2.1 +/- 1.5 kg/m2 vs. -0.3 +/- 1.1 kg/m2), systolic blood pressure (-5.7 +/
      15.3 mmHg vs. -1.6 +/- 13.8 mmHg), 10-year cardiovascular disease risk,
      antidiabetes medication, and quality of life and eating behavior (P < 0.01 for
      all). The effects were maintained long-term. No adverse events were reported.
      CONCLUSIONS: In advanced-stage type 2 diabetes, TeLiPro can improve glycemic
      control and may offer new options to avoid pharmacological intensification.

PMID- 28500215
TI  - A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of
      CDC's National Diabetes Prevention Program.
AB  - OBJECTIVE: To assess participant-level results from the first 4 years of
      implementation of the National Diabetes Prevention Program (National DPP), a
      national effort to prevent type 2 diabetes in those at risk through structured
      lifestyle change programs. RESEARCH DESIGN AND METHODS: Descriptive analysis was
      performed on data from 14,747 adults enrolled in year-long type 2 diabetes
      prevention programs during the period February 2012 through January 2016. Data on
      attendance, weight, and physical activity minutes were summarized and predictors
      of weight loss were examined using a mixed linear model. All analyses were
      performed using SAS 9.3. RESULTS: Participants attended a median of 14 sessions
      over an average of 172 days in the program (median 134 days). Overall, 35.5%
      achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%).
      Participants reported a weekly average of 152 min of physical activity (median
      128 min), with 41.8% meeting the physical activity goal of 150 min per week. For
      every additional session attended and every 30 min of activity reported,
      participants lost 0.3% of body weight (P < 0.0001). CONCLUSIONS: During the first
      4 years, the National DPP has achieved widespread implementation of the lifestyle
      change program to prevent type 2 diabetes, with promising early results. Greater
      duration and intensity of session attendance resulted in a higher percent of body
      weight loss overall and for subgroups. Focusing on retention may reduce
      disparities and improve overall program results. Further program expansion and
      investigation is needed to continue lowering the burden of type 2 diabetes
      nationally.

PMID- 28500218
TI  - NHS in danger of falling behind with out of date scanners, warn experts.

PMID- 28500216
TI  - Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention
      Program Outcomes Study.
AB  - OBJECTIVE: We examined the association of the Diabetes Prevention Program (DPP)
      intervention arms (lifestyle intervention, metformin, and placebo) with cognition
      in the Diabetes Prevention Program Outcomes Study (DPPOS). We also examined
      metformin use, incident type 2 diabetes, and glycemia as exposures. RESEARCH
      DESIGN AND METHODS: The DPP lasted 2.8 years, followed by a 13-month bridge to
      DPPOS. Cognition was assessed in DPPOS years 8 and 10 (12 and 14 years after
      randomization) with the Spanish English Verbal Learning Test (SEVLT), letter
      fluency and animal fluency tests, Digit Symbol Substitution Test (DSST), and a
      composite cognitive score. RESULTS: A total of 2,280 participants (749 lifestyle,
      776 metformin, and 755 placebo) aged 63.1 +/- 10.7 years underwent cognitive
      assessments; 67.7% women, 54.6% non-Hispanic white, 20.7% non-Hispanic black,
      14.6% Hispanic, 5.5% American Indian, and 4.6% Asian; 26.6% were homozygous or
      heterozygous for APOE-epsilon4. At the time of cognitive assessment, type 2
      diabetes was higher in the placebo group (57.9%; P < 0.001) compared with
      lifestyle (47.0%) and metformin (50.4%). Metformin exposure was higher in the
      metformin group (8.72 years; P < 0.001) compared with placebo (1.43 years) and
      lifestyle (0.96 years). There were no differences in cognition across
      intervention arms. Type 2 diabetes was not related to cognition, but higher
      glycated hemoglobin at year 8 was related to worse cognition after confounder
      adjustment. Cumulative metformin exposure was not related to cognition.
      CONCLUSIONS: Exposure to intensive lifestyle intervention or metformin was not
      related to cognition among DPPOS participants. Higher glycemia was related to
      worse cognitive performance. Metformin seemed cognitively safe among DPPOS
      participants.

PMID- 28500217
TI  - Glucose Peaks and the Risk of Dementia and 20-Year Cognitive Decline.
AB  - OBJECTIVE: Hemoglobin A1c (HbA1c), a measure of average blood glucose level, is
      associated with the risk of dementia and cognitive impairment. However, the role
      of glycemic variability or glucose excursions in this association is unclear. We
      examined the association of glucose peaks in midlife, as determined by the
      measurement of 1,5-anhydroglucitol (1,5-AG) level, with the risk of dementia and
      20-year cognitive decline. RESEARCH DESIGN AND METHODS: Nearly 13,000
      participants from the Atherosclerosis Risk in Communities (ARIC) study were
      examined. Dementia was ascertained from surveillance, neuropsychological testing,
      telephone calls with participants or their proxies, or death certificate dementia
      codes. Cognitive function was assessed using three neuropsychological tests at
      three visits over 20 years and was summarized as z scores. We used Cox and linear
      mixed-effects models. 1,5-AG level was dichotomized at 10 MUg/mL and examined
      within clinical categories of HbA1c. RESULTS: Over a median time of 21 years,
      dementia developed in 1,105 participants. Among persons with diabetes, each 5
      MUg/mL decrease in 1,5-AG increased the estimated risk of dementia by 16% (hazard
      ratio 1.16, P = 0.032). For cognitive decline among participants with diabetes
      and HbA1c <7% (53 mmol/mol), those with glucose peaks had a 0.19 greater z score
      decline over 20 years (P = 0.162) compared with those without peaks. Among
      participants with diabetes and HbA1c >=7% (53 mmol/mol), those with glucose peaks
      had a 0.38 greater z score decline compared with persons without glucose peaks (P
      < 0.001). We found no significant associations in persons without diabetes.
      CONCLUSIONS: Among participants with diabetes, glucose peaks are a risk factor
      for cognitive decline and dementia. Targeting glucose peaks, in addition to
      average glycemia, may be an important avenue for prevention.

PMID- 28500219
TI  - Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats.
AB  - Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease,
      causing muscle paralysis and death from respiratory failure. Effective means to
      preserve/restore ventilation are necessary to increase the quality and duration
      of life in ALS patients. At disease end-stage in a rat ALS model (SOD1G93A ),
      acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels
      via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in
      end-stage SOD1G93A rats are not known. Moderate AIH-induced pLTF is normally
      elicited via cellular mechanisms that require the following: Gq-protein-coupled 5
      HT2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q
      pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that
      requires the following: Gs-protein-coupled adenosine 2A receptor activation, new
      TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male
      SOD1G93A rats and wild-type littermates, we investigated relative Q versus S
      pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small
      interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3
      kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats,
      moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or
      PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although
      phrenic motor neuron numbers were decreased in end-stage SOD1G93A rats (~30%
      survival; p < 0.001), BDNF and phosphorylated ERK expression were increased in
      spared phrenic motor neurons (p < 0.05), consistent with increased Q-pathway
      contributions to pLTF. Our results increase understanding of respiratory
      plasticity and its potential to preserve/restore breathing capacity in
      ALS.SIGNIFICANCE STATEMENT Since neuromuscular disorders, such as amyotrophic
      lateral sclerosis (ALS), end life via respiratory failure, the ability to harness
      respiratory motor plasticity to improve breathing capacity could increase the
      quality and duration of life. In a rat ALS model (SOD1G93A ) we previously
      demonstrated that spinal respiratory motor plasticity elicited by acute
      intermittent hypoxia is enhanced at disease end-stage, suggesting greater
      potential to preserve/restore breathing capacity. Here we demonstrate that
      enhanced intermittent hypoxia-induced phrenic motor plasticity results from
      amplification of normal cellular mechanisms versus addition/substitution of
      alternative mechanisms. Greater understanding of mechanisms underlying phrenic
      motor plasticity in ALS may guide development of new therapies to preserve and/or
      restore breathing in ALS patients.

PMID- 28500221
TI  - Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory
      via Its Deubiquitinating Effect on TrkB.
AB  - Multiple studies have established that brain-derived neurotrophic factor (BDNF)
      plays a critical role in the regulation of synaptic plasticity via its receptor,
      TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be
      ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological
      functions remain poorly understood. In this study, we demonstrate that ubiquitin
      C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning learning
      and memory via the regulation of ubiquitination of TrkB. We provide evidence that
      UCH-L1 can deubiquitinate TrkB directly. K460 in the juxtamembane domain of TrkB
      is the primary ubiquitination site and is regulated by UCH-L1. By using a peptide
      that competitively inhibits the association between UCH-L1 and TrkB, we show that
      the blockade of UCH-L1-regulated TrkB deubiquitination leads to increased BDNF
      induced TrkB internalization and consequently directs the internalized TrkB to
      the degradation pathway, resulting in increased degradation of surface TrkB and
      attenuation of TrkB activation and its downstream signaling pathways. Moreover,
      injection of the peptide into the DG region of mice impairs hippocampus-dependent
      memory. Together, our results suggest that the ubiquitination of TrkB is a
      mechanism that controls its downstream signaling pathways via the regulation of
      its endocytosis and postendocytic trafficking and that UCH-L1 mediates the
      deubiquitination of TrkB and could be a potential target for the modulation of
      hippocampus-dependent memory.SIGNIFICANCE STATEMENT Ubiquitin C-terminal
      hydrolase L1 (UCH-L1) has been demonstrated to play important roles in the
      regulation of synaptic plasticity and learning and memory. TrkB, the receptor for
      brain-derived neurotrophic factor, has also been shown to be a potent regulator
      of synaptic plasticity. In this study, we demonstrate that UCH-L1 functions as a
      deubiquitinase for TrkB. The blockage of UCH-L1-regulated deubiquitination of
      TrkB eventually results in the increased degradation of surface TrkB and
      decreased activation of TrkB and its downstream signaling pathways. In vivo, UCH
      L1-regulated TrkB deubiquitination is necessary for hippocampus-dependent memory.
      Overall, our study provides novel insights into the mechanisms of UCH-L1-mediated
      neurobiological functions and suggests that ubiquitination is an important
      regulatory signal for TrkB functions.

PMID- 28500222
TI  - Energy Requirements of Odor Transduction in the Chemosensory Cilia of Olfactory
      Sensory Neurons Rely on Oxidative Phosphorylation and Glycolytic Processing of
      Extracellular Glucose.
AB  - The mechanisms that power the physiological events occurring in cilia, flagella,
      and microvilli are of fundamental importance for the functions of these important
      and ubicuous organelles. The olfactory epithelium is mostly populated by ciliated
      olfactory sensory neurons (OSNs) and surrounding sustentacular cells (SCs) with
      apical microvilli. The only OSN dendrite extends to the surface forming a knob
      projecting several chemosensory cilia of ~50 * 0.2 MUm, devoid of inner membranes
      embedded in a mucus layer. Upon odorant binding, odor receptors couple to G
      protein activating adenylyl cyclase, producing cAMP. cAMP opens cyclic nucleotide
      gated channels allowing a Ca2+ influx that opens Ca2+-activated Cl- channels,
      generating the receptor potential. Many enzymes are activated in
      chemotransduction to hydrolyze ATP. The knob contains approximately two
      mitochondria; assuming that the cilia ATP is 1 mm and diffuses along it at ~10
      MUm in 500 ms, ATP from the knob mitochondria may not fulfill the demands of
      transduction over the full length of the cilium, which suggests an additional ATP
      source. We measured millimolar glucose in rat mucus; we detected glucose
      transporter GLUT3 in rat and toad (Caudiverbera caudiverbera) OSN cilia, SC
      microvilli, and glycolytic enzymes in rat cilia. We also found that the cilia and
      knob can incorporate and accumulate 2-deoxyglucose (glucose analog), but not when
      blocking GLUT. Glucose removal and the inhibition of glycolysis or oxidative
      phospholylation impaired the odor response. This evidence strongly suggests that
      glycolysis in the cilia and knob oxidative phosphorylation together fuel
      chemotransduction.SIGNIFICANCE STATEMENT How processes occurring in cilia and
      flagella are powered is a matter of general interest. Substantial progress has
      been made in unraveling the sensory transduction mechanisms, commonly occurring
      in such structures; however, the energy sources powering them have been scarcely
      explored. Accessibility to the specialized sensory organelles and their small
      dimensions have been limiting factors. Olfactory sensory neurons chemosensory
      cilia are elongated, mucus embedded, fully exposed structures particularly
      amenable for a multidisciplinary study of this problem, as done here. We
      demonstrate the occurrence and functionality of glucose uptake and glycolysis in
      the cilia. We support that odor transduction relies on ATP generated by oxidative
      phosphorylation in the dendrite and glycolytically in the cilia using glucose
      internalized from the mucus.

PMID- 28500220
TI  - Environmental Enrichment Rescues Binocular Matching of Orientation Preference in
      the Mouse Visual Cortex.
AB  - Neural circuits are shaped by experience during critical periods of development.
      Sensory deprivation during these periods permanently compromises an organism's
      ability to perceive the outside world. In the mouse visual system, normal visual
      experience during a critical period in early life drives the matching of
      individual cortical neurons' orientation preferences through the two eyes, likely
      a key step in the development of binocular vision. Here, in mice of both sexes,
      we show that the binocular matching process is completely blocked by monocular
      deprivation spanning the entire critical period. We then show that 3 weeks of
      environmental enrichment (EE), a paradigm of enhanced sensory, motor, and
      cognitive stimulation, is sufficient to rescue binocular matching to the level
      seen in unmanipulated mice. In contrast, 6 weeks of conventional housing only
      resulted in a partial rescue. Finally, we use two-photon calcium imaging to track
      the matching process chronically in individual cells during EE-induced rescue. We
      find that for cells that are clearly dominated by one of the two eyes, the input
      representing the weaker eye changes its orientation preference to align with that
      of the dominant eye. These results thus reveal ocular dominance as a key driver
      of the binocular matching process, and suggest a model whereby the dominant input
      instructs the development of the weaker input. Such a mechanism may operate in
      the development of other systems that need to integrate inputs from multiple
      sources to generate normal neuronal functions.SIGNIFICANCE STATEMENT Critical
      periods are developmental windows of opportunity that ensure the proper wiring of
      neural circuits, as well as windows of vulnerability when abnormal experience
      could cause lasting damage to the developing brain. In the visual system,
      critical period plasticity drives the establishment of binocularly matched
      orientation preferences in cortical neurons. Here, we show that binocular
      matching is completely blocked by monocular deprivation during the critical
      period. Moreover, environmental enrichment can fully rescue the disrupted
      matching, whereas conventional housing of twice the duration results in a partial
      rescue. We then use two-photon calcium imaging to track individual cells
      chronically during the EE-induced recovery, and reveal important insights into
      how appropriate function can be restored to the nervous system after the critical
      period.

PMID- 28500223
TI  - Thirty-Year Mortality After Coronary Artery Bypass Graft Surgery: A Danish
      Nationwide Population-Based Cohort Study.
AB  - BACKGROUND: Data are sparse on long-term mortality after coronary artery bypass
      graft (CABG) surgery. We examined short-term and long-term mortality of patients
      undergoing CABG surgery and a general population comparison cohort. METHODS AND
      RESULTS: Linking data from Danish registries, we conducted a nationwide,
      population-based cohort study on 51 307 CABG patients and 513 070 individuals
      from the general population matched on age, sex, and calendar year (1980-2009).
      The mortality risk was higher in patients having isolated CABG surgery than in
      the general population, particularly during 0 to 30 days (3.2% versus 0.2%), 11
      to 20 years (51.1% versus 35.6%), and 21 to 30 years (62.4% versus 44.8%), but
      not substantially higher during 31 to 364 days (2.9% versus 2.4%) or 1 to 10
      years (30.7% versus 25.8%). The 30-day adjusted mortality rate ratio for isolated
      CABG surgery was 13.51 (95% confidence interval [CI], 12.59-14.49). Between 31 to
      364 days and 1 to 10 years, the isolated CABG surgery cohort had a slightly
      higher mortality rate than the general population comparison cohort, adjusted
      mortality rate ratios of 1.15 (95% CI, 1.09-1.21) and 1.09 (95% CI, 1.08-1.11),
      respectively. Between 11 to 20 years and 21 to 30 years, the adjusted mortality
      rate ratios were 1.62 (95% CI, 1.58-1.66) and 1.76 (95% CI, 1.62-1.91). Within 30
      days, CABG patients had a 25-fold, a 26-fold, and a 18-fold higher risk of dying
      from myocardial infarction, heart failure, or stroke, respectively, than members
      of the general population comparison cohort. We found substantial heterogeneity
      in absolute mortality rates according to baseline risk groups. CONCLUSIONS: The
      isolated CABG cohort had a higher mortality rate than the general population
      comparison cohort, especially within 30 days of and 10 years after surgery.

PMID- 28500225
TI  - Zika virus infection-associated acute transient polyneuritis.

PMID- 28500224
TI  - Evaluating the safety of beta-interferons in MS: A series of nested case-control
      studies.
AB  - OBJECTIVE: To examine the association between interferon-beta (IFN-beta) and
      potential adverse events using population-based health administrative data in
      British Columbia, Canada. METHODS: Patients with relapsing-remitting multiple
      sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis
      Clinic (1995-2004) were eligible for inclusion and were followed up until death,
      absence from British Columbia, exposure to a non-IFN-beta disease-modifying drug,
      or December 31, 2008. Incidence rates were estimated for each potential adverse
      event (selected a priori and defined with ICD-9/10 diagnosis codes from physician
      and hospital claims). A nested case-control study was conducted to assess the
      odds of previous IFN-beta exposure for each potential adverse event with at least
      30 cases. Cases were matched by age (+/-5 years), sex, and year of cohort entry,
      with up to 20 randomly selected (by incidence density sampling) controls. Odds
      ratios (ORs) with 95% confidence intervals (95% CIs) were estimated with
      conditional logistic regression adjusted for age at cohort entry. RESULTS: Of the
      2,485 eligible patients, 77.9% were women, and 1,031 were treated with IFN-beta
      during follow-up. From the incidence analyses, 27 of the 47 potential adverse
      events had at least 30 cases. Patients with incident stroke (ORadj 1.83, 95% CI
      1.16-2.89), migraine (ORadj 1.55, 95% CI 1.18-2.04), depression (ORadj 1.33, 95%
      CI 1.13-1.56), and hematologic abnormalities (ORadj 1.32, 95% CI 1.01-1.72) were
      more likely to have previous exposure to IFN-beta than controls. CONCLUSIONS:
      Among patients with RRMS, IFN-beta was associated with a 1.8- and 1.6-fold
      increase in the risk of stroke and migraine and 1.3-fold increases in depression
      and hematologic abnormalities.

PMID- 28500226
TI  - MR perfusion lesions after TIA or minor stroke are associated with new infarction
      at 7 days.
AB  - OBJECTIVE: To investigate the relationship between acute perfusion-weighted
      imaging (PWI) lesions occurring within the first hours after a TIA or a minor
      brain infarction (BI) and the incidence of new BI detected on a systematic MRI at
      1 week. METHODS: Consecutive patients who experienced a TIA or BI with a
      neurologic deficit that lasted <24 hours, did not receive any revascularization
      therapy (thrombolysis/thrombectomy), and underwent DWI/PWI at baseline and fluid
      attenuated inversion recovery (FLAIR)/DWI 1 week after symptom onset were
      enrolled. Investigators blinded to clinical information independently assessed
      the presence of acute ischemic lesions on baseline DWI/PWI and follow-up DWI and
      FLAIR. Baseline and follow-up MRIs were then compared to determine the occurrence
      and location of new infarctions. RESULTS: Sixty-four patients met the inclusion
      criteria. Median (IQR) ABCD2 score was 4 (3-5). Median delay from onset to
      baseline and follow-up MRI was 5 (2-10) hours and 6 (5-7) days, respectively. MRI
      revealed an acute ischemic lesion on DWI and/or PWI in 38 patients. Nine patients
      (14%) had a new infarction on follow-up MRI. Each had a PWI and 4 had a DWI
      lesion on baseline MRI. All new BIs except one were asymptomatic and in the same
      location as the acute PWI lesion. CONCLUSIONS: Our results showed that 30% of the
      acute focal PWI lesions detected after a TIA are associated with a new BI at 1
      week. Those new BIs may result from the progression of the initial ischemic
      injury.

PMID- 28500228
TI  - A liana from the lower Miocene of Panama and the fossil record of Connaraceae.
AB  - PREMISE OF THE STUDY: Permineralized wood is common in the Miocene beds exposed
      during the expansion of the Panama Canal. We describe a stem with the distinctive
      anatomy of a liana and evaluate the evolutionary, biogeographic, and ecological
      significance of this discovery. METHODS: The object of the study was obtained
      from a collection of fossil woods and fruits from a locality in the lower Miocene
      Cucaracha Formation, where the formation is exposed by the Culebra Cut of the
      Panama Canal. Thin sections were prepared using the cellulose acetate peel
      technique and examined using transmitted light microscopy. We described the
      anatomy and compared it with that of extant and fossil species. We also reviewed
      and evaluated published reports of fossils attributed to Connaraceae. KEY
      RESULTS: The anatomy of this fossil wood matches the genus Rourea (Connaraceae).
      The stem is only 1 cm in diameter, but vessels >200 MUm in diameter also occur,
      indicating the perennial climbing habit. We evaluated 12 other pre-Quaternary
      occurrences attributed to Connaraceae. Four are accepted, three are rejected, and
      we consider five unknown or uncertain. CONCLUSIONS: The discovery of this Rourea
      stem confirms the presence of Connaraceae in the Neotropics by the early Miocene,
      provides the oldest evidence of the climbing habit in the family, and contributes
      to our understanding of the flora of Panama 19 mya. Although the fossil record of
      Connaraceae is sparse, reliable occurrences span three continents and indicate
      that the family originated as early as the Late Cretaceous-Paleocene and was
      widespread by the early Miocene.

PMID- 28500227
TI  - Neurofilament markers for ALS correlate with extent of upper and lower motor
      neuron disease.
AB  - OBJECTIVE: To determine the diagnostic performance and prognostic value of
      phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain
      (NfL) in CSF as possible biomarkers for amyotrophic lateral sclerosis (ALS) at
      the diagnostic phase. METHODS: We measured CSF pNfH and NfL concentrations in 220
      patients with ALS, 316 neurologic disease controls (DC), and 50 genuine disease
      mimics (DM) to determine and assess the accuracy of the diagnostic cutoff value
      for pNfH and NfL and to correlate with other clinical parameters. RESULTS: pNfH
      was most specific for motor neuron disease (specificity 88.2% [confidence
      interval (CI) 83.0%-92.3%]). pNfH had the best performance to differentially
      diagnose patients with ALS from DM with a sensitivity of 90.7% (CI 84.9%-94.8%),
      a specificity of 88.0% (CI 75.7%-95.5%) and a likelihood ratio of 7.6 (CI 3.6
      16.0) at a cutoff of 768 pg/mL. CSF pNfH and NfL levels were significantly lower
      in slow disease progressors, however, with a poor prognostic performance with
      respect to the disease progression rate. CSF pNfH and NfL levels increased
      significantly as function of the number of regions with both upper and lower
      motor involvement. CONCLUSIONS: In particular, CSF pNfH concentrations show an
      added value as diagnostic biomarkers for ALS, whereas the prognostic value of
      pNfH and NfL warrants further investigation. Both pNfH and NfL correlated with
      the extent of motor neuron degeneration. CLASSIFICATION OF EVIDENCE: This study
      provides Class II evidence that elevated concentrations of CSF pNfH and NfL can
      accurately identify patients with ALS.

PMID- 28500229
TI  - Isolation by distance and isolation by environment contribute to population
      differentiation in Protea repens (Proteaceae L.), a widespread South African
      species.
AB  - PREMISE OF THE STUDY: The Cape Floristic Region (CFR) of South Africa is renowned
      for its botanical diversity, but the evolutionary origins of this diversity
      remain controversial. Both neutral and adaptive processes have been implicated in
      driving diversification, but population-level studies of plants in the CFR are
      rare. Here, we investigate the limits to gene flow and potential environmental
      drivers of selection in Protea repens L. (Proteaceae L.), a widespread CFR
      species. METHODS: We sampled 19 populations across the range of P. repens and
      used genotyping by sequencing to identify 2066 polymorphic loci in 663
      individuals. We used a Bayesian FST outlier analysis to identify single
      nucleotide polymorphisms (SNPs) marking genomic regions that may be under
      selection; we used those SNPs to identify potential drivers of selection and
      excluded them from analyses of gene flow and genetic structure. RESULTS: A
      pattern of isolation by distance suggested limited gene flow between nearby
      populations. The populations of P. repens fell naturally into two or three
      groupings, which corresponded to an east-west split. Differences in rainfall
      seasonality contributed to diversification in highly divergent loci, as do
      barriers to gene flow that have been identified in other species. CONCLUSIONS:
      The strong pattern of isolation by distance is in contrast to the findings in the
      only other widespread species in the CFR that has been similarly studied, while
      the effects of rainfall seasonality are consistent with well-known patterns.
      Assessing the generality of these results will require investigations of other
      CFR species.

PMID- 28500230
TI  - Conjunctival lymphangiectasia associated with classic Fabry disease.
AB  - BACKGROUND: Fabry disease (FD) is a treatable multisystem disease caused by a
      defect in the alpha-galactosidase gene. Ocular signs of FD, including corneal
      verticillata, are among the earliest diagnostic findings. Conjunctival
      lymphangiectasia (CL) has not previously been associated with FD. METHODS: We
      examined the eyes of a cohort of 13 adult patients, eight men and five women,
      with documented classic FD, all treated with enzyme replacement therapy (ERT) at
      the University of Alabama at Birmingham between February 2014 and April 2015. The
      average age was 48 years with a range of 35-55 years for men and 21-71 years for
      women. The mean duration of ERT was 8.4 years (men 8.9 years, women 7.6 years)
      with a range of 4-14 years. Classical Fabry mutations included Q283X, R227X,
      W236X and W277X. A high resolution Haag-Streit BQ-900 slit lamp with EyeCap
      imaging system was used to record conjunctival images. RESULTS: CL was observed
      in 11 of the 13 patients (85%) despite long-term ERT. Clinical presentations
      included single cysts, beaded dilatations and areas of conjunctival oedema.
      Lesions were located within 6 mm of the corneal limbus. Ten of the 13 subjects
      (77%) had Fabry-related cataracts and all 13 demonstrated bilateral corneal
      verticillata. Twelve of the 13 patients had evidence of dry eye, 9 of whom were
      symptomatic, and 10 had peripheral lymphoedema. CONCLUSION: CL represents a
      common but under-recognised ocular manifestation of FD, which persists despite
      ERT, and is often accompanied by peripheral lymphoedema and dry eye syndrome.

PMID- 28500231
TI  - Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A-beta-Catenin
      Signaling and Restricts Tumor Growth and Metastasis.
AB  - Molecular hybridization of different pharmacophores to tackle both tumor growth
      and metastasis by a single molecular entity can be very effective and unique if
      the hybrid product shows drug-like properties. Here, we report synthesis and
      discovery of a novel small-molecule inhibitor of PP2A-beta-catenin signaling that
      limits both in vivo tumor growth and metastasis. Our molecular hybridization
      approach resulted in cancer cell selectivity and improved drug-like properties of
      the molecule. Inhibiting PP2A and beta-catenin interaction by selectively
      engaging PR55alpha-binding site, our most potent small-molecule inhibitor
      diminished the expression of active beta-catenin and its target proteins c-Myc
      and Cyclin D1. Furthermore, it promotes robust E-cadherin upregulation on the
      cell surface and increases beta-catenin-E-Cadherin association, which may prevent
      dissemination of metastatic cells. Altogether, we report synthesis and
      mechanistic insight of a novel drug-like molecule to differentially target beta
      catenin functionality via interacting with a particular subunit of PP2A. Mol
      Cancer Ther; 16(9); 1791-805. (c)2017 AACR.

PMID- 28500232
TI  - NKG2D Ligand-Targeted Bispecific T-Cell Engagers Lead to Robust Antitumor
      Activity against Diverse Human Tumors.
AB  - Two new bispecific T-cell engaging (BiTE) molecules with specificity for NKG2D
      ligands were developed and functionally characterized. One, huNKG2D-OKT3, was
      derived from the extracellular portion of the human NKG2D receptor fused to a
      CD3epsilon binding single-chain variable fragment (scFv), known as OKT3. NKG2D
      has multiple ligands, including MICA, which are expressed by a variety of
      malignant cells. A second molecule, B2-OKT3, was created in the tandem scFv BiTE
      format that targets MICA on tumor cells and CD3epsilon on human T cells. Both
      BiTEs specifically activated T cells to kill human tumor cell lines. Cytotoxicity
      by B2-OKT3, but not huNKG2D-OKT3, is blocked by soluble rMICA. The huNKG2D-OKT3
      induced greater T-cell cytokine production in comparison with B2-OKT3. No T-cell
      pretreatment was required for IFNgamma production upon coculture of B2-OKT3 or
      huNKG2D-OKT3 with T cells and target cells. The effector memory T-cell
      compartment was the primary source of IFNgamma, and culture of T cells and these
      BiTEs with plate-bound rMICA showed ligand density-dependent production of
      IFNgamma from both CD4+ and CD8+ T cells. There was 2-fold more IFNgamma produced
      per CD8+ T cell and 5-fold greater percentage of CD8+ T cells producing IFNgamma
      compared with CD4+ T cells. In addition, both BiTEs elicited significant
      antitumor responses against human metastatic melanoma tumor samples using
      autologous or healthy donor T cells. These data demonstrate the robust antitumor
      activity of these NKG2D ligand-binding bispecific proteins and support their
      further development for clinical use. Mol Cancer Ther; 16(7); 1335-46. (c)2017
      AACR.

PMID- 28500233
TI  - Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53
      Deficient Prostate Cancer to Radiation.
AB  - The use of PARP inhibitors in combination with radiotherapy is a promising
      strategy to locally enhance DNA damage in tumors. Here we show that radiation
      resistant cells and tumors derived from a Pten/Trp53-deficient mouse model of
      advanced prostate cancer are rendered radiation sensitive following treatment
      with NanoOlaparib, a lipid-based injectable nanoformulation of olaparib. This
      enhancement in radiosensitivity is accompanied by radiation dose-dependent
      changes in gamma-H2AX expression and is specific to NanoOlaparib alone. In
      animals, twice-weekly intravenous administration of NanoOlaparib results in
      significant tumor growth inhibition, whereas previous studies of oral olaparib as
      monotherapy have shown no therapeutic efficacy. When NanoOlaparib is administered
      prior to radiation, a single dose of radiation is sufficient to triple the median
      mouse survival time compared to radiation only controls. Half of mice treated
      with NanoOlaparib + radiation achieved a complete response over the 13-week study
      duration. Using ferumoxytol as a surrogate nanoparticle, MRI studies revealed
      that NanoOlaparib enhances the intratumoral accumulation of systemically
      administered nanoparticles. NanoOlaparib-treated tumors showed up to 19-fold
      higher nanoparticle accumulation compared to untreated and radiation-only
      controls, suggesting that the in vivo efficacy of NanoOlaparib may be potentiated
      by its ability to enhance its own accumulation. Together, these data suggest that
      NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity
      of radiation-resistant tumors lacking BRCA mutations, such as those with PTEN and
      TP53 deletions. Mol Cancer Ther; 16(7); 1279-89. (c)2017 AACR.

PMID- 28500234
TI  - Niclosamide and Bicalutamide Combination Treatment Overcomes Enzalutamide- and
      Bicalutamide-Resistant Prostate Cancer.
AB  - Activation of the androgen receptor (AR) and its splice variants is linked to
      advanced prostate cancer and drives resistance to antiandrogens. The roles of AR
      and AR variants in the development of resistance to androgen deprivation therapy
      (ADT) and bicalutamide treatment, however, are still incompletely understood. To
      determine whether AR variants play a role in bicalutamide resistance, we
      developed bicalutamide-resistant LNCaP cells (LNCaP-BicR) and found that these
      resistant cells express significantly increased levels of AR variants,
      particularly AR-V7, both at the mRNA and protein levels. Exogenous expression of
      AR-V7 in bicalutamide-sensitive LNCaP cells confers resistance to bicalutamide
      treatment. Knockdown of AR-V7 in bicalutamide- and enzalutamide-resistant
      CWR22Rv1, enzalutamide-resistant C4-2B (C4-2B MDVR), and LNCaP-BicR cells
      reversed bicalutamide resistance. Niclosamide, a potent inhibitor of AR variants,
      significantly enhanced bicalutamide treatment. Niclosamide and bicalutamide
      combination treatment not only suppressed AR and AR variants expression and
      inhibited their recruitment to the PSA promoter, but also significantly induced
      apoptosis in bicalutamide- and enzalutamide-resistant CWR22Rv1 and C4-2B MDVR
      cells. In addition, combination of niclosamide with bicalutamide inhibited the
      growth of enzalutamide-resistant tumors. In summary, our results demonstrate that
      AR variants, particularly AR-V7, drive bicalutamide resistance and that targeting
      AR-V7 with niclosamide can resensitize bicalutamide-resistant cells to
      bicalutamide treatment. Furthermore, combination of niclosamide with bicalutamide
      inhibits enzalutamide resistant tumor growth, suggesting that the combination of
      niclosamide and bicalutamide could be a potential cost-effective strategy to
      treat advanced prostate cancer in patients, including those who fail to respond
      to enzalutamide therapy. Mol Cancer Ther; 16(8); 1521-30. (c)2017 AACR.

PMID- 28500235
TI  - beta-Catenin Inhibitor BC2059 Is Efficacious as Monotherapy or in Combination
      with Proteasome Inhibitor Bortezomib in Multiple Myeloma.
AB  - Currently available treatment options are unlikely to be curative for the
      majority of multiple myeloma patients, emphasizing a continuing role for the
      introduction of investigational agents that can overcome drug resistance. The
      canonical Wnt/beta-catenin signaling pathway, essential for self-renewal, growth,
      and survival, has been found to be dysregulated in multiple myeloma, particularly
      in advanced stages of disease. This provides the rationale for evaluating the
      novel beta-catenin inhibitor BC2059 as monotherapy and in combination with
      proteasome inhibitors in vitro and in vivo Here, we show nuclear localization of
      beta-catenin in human myeloma cell lines (HMCL), consistent with activation of
      the canonical Wnt pathway. BC2059 attenuates beta-catenin levels, in both the
      cytoplasm and the nucleus, reducing the transcriptional activity of the TCF4/LEF
      complex and the expression of its target gene axin 2. Treatment of HMCL with
      BC2059 inhibits proliferation and induces apoptosis in a dose-dependent manner.
      This is also observed in HMCL-stromal cell cocultures, mitigating the protective
      effect afforded by the stroma. Similarly, BC2059 induces apoptosis in primary
      multiple myeloma samples in vitro, causing minimal apoptosis on healthy
      peripheral blood mononuclear cells. Furthermore, it synergizes with the
      proteasome inhibitor bortezomib both in HMCL and primary multiple myeloma
      samples. Finally, in xenograft models of human myelomatosis, BC2059 delays tumor
      growth and prolongs survival with minor on-target side effects. Collectively,
      these results demonstrate the efficacy of targeting the Wnt/beta-catenin pathway
      with BC2059 both in vitro and in vivo, at clinically achievable doses. These
      findings support further clinical evaluation of BC2059 for the treatment of
      multiple myeloma. Mol Cancer Ther; 16(9); 1765-78. (c)2017 AACR.

PMID- 28500236
TI  - Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF
      Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer
      Cells.
AB  - Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors
      (BRAFi). In this study, we identified serine biosynthesis as a critical mechanism
      of resistance. Proteomic assays revealed differential protein expression of
      serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi)
      treatment in sensitive versus acquired resistant melanoma cells. Ablation of
      PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting
      the folate cycle, directly downstream of serine synthesis, with methotrexate also
      displayed similar sensitization. Using the DNA-damaging drug gemcitabine, we show
      that gemcitabine pretreatment sensitized resistant melanoma cells to BRAFis
      vemurafenib and dabrafenib. We extended our findings to BRAF WT tumor cell lines
      that are intrinsically resistant to vemurafenib and dabrafenib. Pretreatment of
      pancreatic cancer and non-small cell lung cancer cell lines with sublethal doses
      of 50 and 5 nmol/L of gemcitabine, respectively, enhanced killing by both
      vemurafenib and dabrafenib. The novel aspects of this study are the direct
      identification of serine biosynthesis as a critical mechanism of BRAF V600E
      inhibitor resistance and the first successful example of using gemcitabine +
      BRAFis in combination to kill previously drug-resistant cancer cells, creating
      the translational potential of pretreatment with gemcitabine prior to BRAFi
      treatment of tumor cells to reverse resistance within the mutational profile and
      the WT. Mol Cancer Ther; 16(8); 1596-609. (c)2017 AACR.

PMID- 28500238
TI  - SDHA mutated paragangliomas may be at high risk of metastasis.

PMID- 28500239
TI  - Vacuolar and plasma membrane proton pumps collaborate to achieve cytosolic pH
      homeostasis in yeast.

PMID- 28500237
TI  - Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation
      of RAS/MAPK Signaling.
AB  - Oncogenic rearrangements in RET are present in 1%-2% of lung adenocarcinoma
      patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency
      against the RET kinase domain. Here, we demonstrate that ponatinib exhibits
      potent antiproliferative activity in RET fusion-positive LC-2/ad lung
      adenocarcinoma cells and inhibits phosphorylation of the RET fusion protein and
      signaling through ERK1/2 and AKT. Using distinct dose escalation strategies, two
      ponatinib-resistant LC-2/ad cell lines, PR1 and PR2, were derived. PR1 and PR2
      cell lines retained expression, but not phosphorylation of the RET fusion and
      lacked evidence of a resistance mutation in the RET kinase domain. Both resistant
      lines retained activation of the MAPK pathway. Next-generation RNA sequencing
      revealed an oncogenic NRAS p.Q61K mutation in the PR1 cell. PR1 cell
      proliferation was preferentially sensitive to siRNA knockdown of NRAS compared
      with knockdown of RET, more sensitive to MEK inhibition than the parental line,
      and NRAS dependence was maintained in the absence of chronic RET inhibition.
      Expression of NRAS p.Q61K in RET fusion expressing TPC1 cells conferred
      resistance to ponatinib. PR2 cells exhibited increased expression of EGFR and
      AXL. EGFR inhibition decreased cell proliferation and phosphorylation of ERK1/2
      and AKT in PR2 cells, but not LC-2/ad cells. Although AXL inhibition enhanced PR2
      sensitivity to afatinib, it was unable to decrease cell proliferation by itself.
      Thus, EGFR and AXL cooperatively rescued signaling from RET inhibition in the PR2
      cells. Collectively, these findings demonstrate that resistance to ponatinib in
      RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms
      that result in restored RAS/MAPK activation. Mol Cancer Ther; 16(8); 1623-33.
      (c)2017 AACR.

PMID- 28500240
TI  - A carboxyl ester lipase (CEL) mutant causes chronic pancreatitis by forming
      intracellular aggregates that activate apoptosis.

PMID- 28500241
TI  - A plague of actin disassembly.
AB  - Pathogenic Yersinia species employ several strategies to evade the host immune
      system, including interfering with cytoskeletal remodeling as a way to block
      macrophage phagocytosis. The kinase YopO binds directly to monomeric actin and
      phosphorylates the actin-remodeling protein gelsolin, but the functional
      importance of this gelsolin modification has not been clear. A combined
      biochemical, computational, and biophysical study now reveals that YopO-mediated
      phosphorylation activates host gelsolin, leading to severed actin filaments and
      disturbed actin dynamics.

PMID- 28500242
TI  - Rotational atherectomy: re-emergence of an old technique.

PMID- 28500243
TI  - Aerobic fitness, muscular strength and obesity in relation to risk of heart
      failure.
AB  - OBJECTIVE: Low physical fitness and obesity have been associated with higher risk
      of developing heart failure (HF), but their interactive effects are unknown.
      Elucidation of interactions among these common modifiable factors may help
      facilitate more effective primary prevention. METHODS: We conducted a national
      cohort study to examine the interactive effects of aerobic fitness, muscular
      strength and body mass index (BMI) among 1 330 610 military conscripts in Sweden
      during 1969-1997 (97%-98% of all 18-year-old men) on risk of HF identified from
      inpatient and outpatient diagnoses through 2012 (maximum age 62 years). RESULTS:
      There were 11 711 men diagnosed with HF in 37.8 million person-years of follow
      up. Low aerobic fitness, low muscular strength and obesity were independently
      associated with higher risk of HF, after adjusting for each other, socioeconomic
      factors, other chronic diseases and family history of HF. The combination of low
      aerobic fitness and low muscular strength (lowest vs highest tertiles) was
      associated with a 1.7-fold risk of HF (95% CI 1.6 to 1.9; p<0.001; incidence
      rates per 100 000 person-years, 43.2 vs 10.8). These factors had positive
      additive and multiplicative interactions (p<0.001) and were associated with
      increased risk of HF even among men with normal BMI. CONCLUSIONS: Low aerobic
      fitness, low muscular strength and obesity at the age of 18 years were
      independently associated with higher risk of HF in adulthood, with interactive
      effects between aerobic fitness and muscular strength. These findings suggest
      that early-life interventions may help reduce the long-term risk of HF and should
      include both aerobic fitness and muscular strength, even among persons with
      normal BMI.

PMID- 28500244
TI  - Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible
      mechanism for steatosis development.
AB  - CONTEXT: Growth hormone (GH) stimulates hepatic synthesis of very-low-density
      lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH
      deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of
      which is not known. As tamoxifen inhibits the secretion and action of GH, we
      hypothesize that it induces steatosis by inhibiting hepatic VLDL export. AIM: To
      investigate whether tamoxifen reduces hepatic VLDL secretion. DESIGN: Eight
      healthy, normolipidemic women (age: 64.4 +/- 2.1 years) were studied in random
      sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of
      estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout
      period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL
      particles, were measured using a stable isotope 2H3-leucine turnover technique.
      VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment
      model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB
      concentration. GH response to arginine stimulation, circulating levels of IGF-1,
      FFA, and TG, along with TG content in VLDL were measured. RESULTS: Tamoxifen
      significantly (P < 0.05) reduced VLDL-apoB concentration and secretion by 27.3 +/
      7.8% and 29.8 +/- 10.2%, respectively. In contrast, EV did not significantly
      change VLDL-apoB concentration or secretion. Tamoxifen but not EV significantly
      reduced (P < 0.05) GH response to arginine stimulation. Both treatments
      significantly lowered (P < 0.05) circulating IGF-1. CONCLUSION: Inhibition of
      VLDL secretion may contribute to the development of fatty liver during tamoxifen
      therapy. As GH stimulates VLDL secretion, the development of steatosis may arise
      secondarily from GH insufficiency induced by tamoxifen.

PMID- 28500245
TI  - Pseudoacromegaly: an unusual presenting manifestation of long-standing
      undiagnosed primary hypothyroidism.

PMID- 28500246
TI  - Closing the theory to practice gap for newly qualified doctors: evaluation of a
      peer-delivered practical skills training course for newly qualified doctors in
      preparation for clinical practice.
AB  - PURPOSE: The Good Intern Programme (GIP) in Sri Lanka has been implemented to
      bridge the 'theory to practice gap' of doctors preparing for their internship.
      This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills
      Training (ACST) course as part of the GIP. STUDY DESIGN: The ACST course was
      developed by an interprofessional faculty, including newly graduated doctors
      awaiting internship (pre-intern), focusing on the recognition and management of
      common medical and surgical emergencies. Course delivery was entirely by pre
      intern doctors to their peers. Knowledge was evaluated by a pre- and post-course
      multiple choice test. Participants' confidence (post-course) and 12 acute care
      skills (pre- and post-course) were assessed using Likert scale-based questions. A
      subset of participants provided feedback on the peer learning experience.
      RESULTS: Seventeen courses were delivered by a faculty consisting of eight peer
      trainers over 4 months, training 320 participants. The mean (SD) multiple choice
      questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post
      course (p<0.05). Increased overall confidence in managing ward emergencies was
      reported by 97.2% (n=283) of respondents. Participants rated their post-course
      skills to be significantly higher (p<0.05) than pre-course in all 12 assessed
      skills. Extended feedback on the peer learning experience was overwhelmingly
      positive and 96.5% would recommend the course to a colleague. CONCLUSIONS: A peer
      delivered ACST course was extremely well received and can improve newly qualified
      medical graduates' knowledge, skills and confidence in managing medical and
      surgical emergencies. This peer-based model may have utility beyond pre-interns
      and beyond Sri Lanka.

PMID- 28500248
TI  - The association of the lipidomic profile with features of polycystic ovary
      syndrome.
AB  - Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women
      with reproductive and metabolic complications. While lipidomics can identify
      associations between lipid species and metabolic diseases, no research has
      examined the association of lipid species with the pathophysiological features of
      PCOS. The aim of this study was to examine the lipidomic profile in women with
      and without PCOS. This study was a cross-sectional study in 156 age-matched pre
      menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without
      PCOS). Outcomes included the association between the plasma lipidomic profile
      (325 lipid species (24 classes) using liquid chromatography mass spectrometry)
      and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex
      hormone-binding globulin (SHBG) and free androgen index (FAI). There were no
      associations of the lipidomic profile with PCOS or testosterone. HOMA was
      positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG
      was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI
      was positively associated with 8 classes (ceramide, phosphatidylcholine,
      lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine,
      phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference
      was associated with 8 classes (4 positively (dihydroceramide,
      phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely
      (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and
      alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to
      central adiposity and FAI in women with or without PCOS. This supports prior
      findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights
      the need for weight management through lifestyle interventions.

PMID- 28500249
TI  - Maternal high-fat diet induces metabolic stress response disorders in offspring
      hypothalamus.
AB  - Maternal obesity has been shown to increase the risk of obesity and related
      disorders in the offspring, which has been partially attributed to changes of
      appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic
      reticulum (ER) stress and autophagy have been implicated in hypothalamic
      neuropeptide dysregulation, thus may also play important roles in such
      transgenerational effect. In this study, we show that offspring born to high-fat
      diet-fed dams showed significantly increased body weight and glucose intolerance,
      adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of
      the orexigenic neuropeptide Y (NPY) was increased, while the levels of the
      anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin
      4 receptor (MC4R) were significantly downregulated. In association, the
      expression of unfolded protein response (UPR) markers including glucose-regulated
      protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4
      was reduced. By contrast, protein levels of autophagy-related genes Atg5 and
      Atg7, as well as mitophagy marker Parkin, were slightly increased. The
      administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein
      folding and UPR activator, in the offspring from postnatal day 4 significantly
      reduced their body weight, fat deposition, which were in association with
      increased activating transcription factor (ATF)4, immunoglobulin-binding protein
      (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase
      (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These
      results suggest that hypothalamic ER stress and mitophagy are among the
      regulatory factors of offspring metabolic changes due to maternal obesity.

PMID- 28500250
TI  - Characterization of NMB, GRP and their receptors (BRS3, NMBR and GRPR) in
      chickens.
AB  - The two structurally and functionally related peptides, gastrin-releasing peptide
      (GRP) and neuromedin B (NMB) play critical roles in many
      physiological/pathological processes in mammals. However, the information
      regarding the expression and functionality of avian NMB, GRP and their receptors
      is limited. Here, we characterized cNMB, cGRP and their receptors (cNMBR, cGRPR
      and cBRS3) in chickens. Our results showed that: (1) cNMBR and cGRPR expressed in
      CHO cells could be potently activated by cNMB and cGRP, respectively, as
      monitored by cell-based luciferase reporter assays, indicating that cNMBR and
      cGRPR are cNMB- and cGRP-specific receptors; strikingly, BRS3 of chickens
      (/spotted gars), which is orthologous to mouse bombesin receptor subtype-3
      (BRS3), could be potently activated by GRP and NMB, demonstrating that both
      peptides are the endogenous ligands for chicken (/spotted gar) BRS3; (2)
      quantitative real-time PCR (qPCR) revealed that cGRPR is widely expressed in
      chicken tissues with abundant expression in the ovary, pancreas, proventriculus,
      spinal cord and brain, whereas cNMB, cNMBR and cBRS3 are mainly expressed in the
      brain and testes; (3) interestingly, qPCR, Western blot and immunostaining
      revealed that cGRP is predominantly expressed in the anterior pituitary and
      mainly localized to LH-cells, suggesting that cGRP is likely a novel pituitary
      hormone in chickens. In summary, our data help to uncover the roles of GRP, NMB
      and their receptors in birds, and provide the first persuasive evidence from an
      evolutionary prospective that in vertebrates, GRP and NMB are the endogenous
      ligands for BRS3, an orphan receptor that has puzzled endocrinologists for more
      than two decades.

PMID- 28500252
TI  - Transcriptome profiling reveals novel BMI- and sex-specific gene expression
      signatures for human cardiac hypertrophy.
AB  - How obesity or sex may affect the gene expression profiles of human cardiac
      hypertrophy is unknown. We hypothesized that body-mass index (BMI) and sex can
      affect gene expression profiles of cardiac hypertrophy. Human heart tissues were
      grouped according to sex (male, female), BMI (lean<25 kg/m2, obese>30 kg/m2), or
      left ventricular hypertrophy (LVH) and non-LVH nonfailed controls (NF). We
      identified 24 differentially expressed (DE) genes comparing female with male
      samples. In obese subgroup, there were 236 DE genes comparing LVH with NF; in
      lean subgroup, there were seven DE genes comparing LVH with NF. In female
      subgroup, we identified 1,320 significant genes comparing LVH with NF; in male
      subgroup, there were 1,383 significant genes comparing LVH with NF. There were
      seven significant genes comparing obese LVH with lean NF; comparing male obese
      LVH with male lean NF samples we found 106 significant genes; comparing female
      obese LVH with male lean NF, we found no significant genes. Using absolute value
      of log2 fold-change > 2 or extremely small P value (10-20) as a criterion, we
      identified nine significant genes (HBA1, HBB, HIST1H2AC, GSTT1, MYL7, NPPA, NPPB,
      PDK4, PLA2G2A) in LVH, also found in published data set for ischemic and dilated
      cardiomyopathy in heart failure. We identified a potential gene expression
      signature that distinguishes between patients with high BMI or between men and
      women with cardiac hypertrophy. Expression of established biomarkers atrial
      natriuretic peptide A (NPPA) and B (NPPB) were already significantly increased in
      hypertrophy compared with controls.

PMID- 28500251
TI  - Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during
      zebrafish development.
AB  - There is mounting evidence that the ribosome is not a static translation
      machinery, but a cell-specific, adaptive system. Ribosomal variations have mostly
      been studied at the protein level, even though the essential transcriptional
      functions are primarily performed by rRNAs. At the RNA level, oocyte-specific 5S
      rRNAs are long known for Xenopus. Recently, we described for zebrafish a similar
      system in which the sole maternal-type 5S rRNA present in eggs is replaced
      completely during embryonic development by a somatic-type. Here, we report the
      discovery of an analogous system for the 45S rDNA elements: 5.8S, 18S, and 28S.
      The maternal-type 5.8S, 18S, and 28S rRNA sequences differ substantially from
      those of the somatic-type, plus the maternal-type rRNAs are also replaced by the
      somatic-type rRNAs during embryogenesis. We discuss the structural and functional
      implications of the observed sequence differences with respect to the
      translational functions of the 5.8S, 18S, and 28S rRNA elements. Finally, in
      silico evidence suggests that expansion segments (ES) in 18S rRNA, previously
      implicated in ribosome-mRNA interaction, may have a preference for interacting
      with specific mRNA genes. Taken together, our findings indicate that two distinct
      types of ribosomes exist in zebrafish during development, each likely conducting
      the translation machinery in a unique way.

PMID- 28500255
TI  - Balancing Bleeding and Clotting: The Known Unknowns of Mechanically Assisted
      Circulation.

PMID- 28500253
TI  - LINC00341 exerts an anti-inflammatory effect on endothelial cells by repressing
      VCAM1.
AB  - The long noncoding RNAs (lncRNAs), which constitute a large portion of the
      transcriptome, have gained intense research interest because of their roles in
      regulating physiological and pathophysiological functions in the cell. We
      identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical
      vein endothelial cells (HUVECs) that are differentially regulated by
      atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated
      lncRNAs, including both known and novel transcripts, LINC00341 is one of the most
      abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced
      by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of
      LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1)
      and the adhesion of monocytes induced by atheroprone flow and tumor necrosis
      factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer
      of zest homolog 2, a core histone methyltransferase of polycomb repressive
      complex 2, to the promoter region of the VCAM1 gene to suppress VCAM1. Network
      analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co
      regulated with LINC00341 in endothelial cells in response to pulsatile shear.
      Together, these findings suggest that LINC00341, as an example of lncRNAs, plays
      important roles in modulating endothelial function in health and disease.

PMID- 28500256
TI  - TZAP-ing telomeres down to size.
AB  - The phenomenon of gradual telomere shortening has become a paradigm for how we
      understand the biology of aging and cancer. Cell proliferation is accompanied by
      cumulative telomere loss, and the aged cell either senesces, dies or transforms
      toward cancer. This transformation requires the activation of telomere elongation
      mechanisms in order to restore telomere length such that cell death or senescence
      programs are not induced. Most of the time, this occurs through telomerase
      reactivation. In other rare cases, the Alternative lengthening of telomeres (ALT)
      pathway hijacks DNA recombination-associated mechanisms to hyperextend telomeres,
      often to more than 50 kb. Why telomere length is restricted and what sets their
      maximal length has been a long-standing puzzle in cell biology. Two recent
      studies published in this issue of EMBO Reports [1] and recently in Science [2]
      sought to address this important question. Both built on omics approaches that
      identified ZBTB48 as a potential telomere-associated protein and reveal it to be
      a critical regulator of telomere length homeostasis by the telomere trimming
      mechanism. These discoveries provide fundamental insights for our understanding
      of telomere trimming and how it impacts telomere integrity in stem and cancer
      cells.

PMID- 28500254
TI  - Increased Thromboembolic Events With Dabigatran Compared With Vitamin K
      Antagonism in Left Ventricular Assist Device Patients: A Randomized Controlled
      Pilot Trial.
AB  - BACKGROUND: Left ventricular assist device-supported patients are usually
      anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term
      vitamin K antagonist therapy can be complicated by unstable international
      normalized ratio values and patient-related compliance problems. Therefore,
      direct thrombin inhibitors may represent an alternative to vitamin K antagonists.
      METHODS AND RESULTS: Thirty HeartWare ventricular assist device patients with
      stable renal function were planned for this prospective, randomized, open-label,
      single-center study. Patients were randomized to receive either phenprocoumon or
      dabigatran in addition to aspirin for long-term anticoagulation. Treatment
      duration was scheduled for 1 year and stopped after observation of a primary end
      point. Dabigatran dose was 110 and 75 mg BID in patients with normal or impaired
      renal function (glomerular filtration rate >80 mL/min or between 80 and 30
      mL/min, respectively). The study was stopped prematurely for safety reasons after
      16 patients (61+/-8 years, 1 female) were randomized. Thromboembolic events
      occurred in 4 subjects receiving dabigatran (50%) and in 1 receiving
      phenprocoumon (13%; P=0.28). No major bleeding was recorded, and no patient died
      during the study. Median time to treatment termination was significantly shorter
      in dabigatran patients (8.5 versus 12.0 months; P=0.015). CONCLUSIONS:
      Thromboembolic events on dabigatran led to early termination of a randomized
      controlled trial of dabigatran versus phenprocoumon in left ventricular assist
      device patients. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov.
      Unique identifier: NCT02872649.

PMID- 28500259
TI  - Central serous chorioretinopathy secondary to tuberculosis: cause or coincidence.
AB  - 32-year-old male with diagnosis of central serous chorioretinopathy (CSCR) in
      both eyes and negative history of administration of any medicine was treated with
      bilateral focal laser at leakage point, with visual recovery. Recurrence occurred
      after 2 years in right eye and was treated successfully with acetazolamide.
      Second recurrence occurred after 1 year. Acetazolamide was restarted, but no
      improvement was noted. Thorough re-evaluation of the patient revealed a family
      history of tuberculosis. Ancillary investigations rendered the presumptive
      diagnosis of tuberculosis, and antituberculosis treatment led to visual recovery
      with no recurrences. Present case poses two dilemmas: whether CSCR was secondary
      to tuberculosis or was it an incidental association in tuberculosis endemic
      population and second whether resolution occurred due to the treatment of
      tuberculosis or due to mineralo-corticoid antagonism action of rifampicin.
      Significance of patient's history, clinical observation and angiographic studies
      in the diagnosis of idiopathic and recurrent CSCR is reiterated.

PMID- 28500257
TI  - ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional
      activator.
AB  - Telomeres constitute the ends of linear chromosomes and together with the
      shelterin complex form a structure essential for genome maintenance and
      stability. In addition to the constitutive binding of the shelterin complex,
      other direct, yet more transient interactions are mediated by the CST complex and
      HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F
      transcription factors. Recently, the Kruppel-like zinc finger protein
      ZBTB48/HKR3/TZAP has been described as a novel telomere-associated factor in the
      vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric
      and to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of
      human cancer cells regardless of the mode of telomere maintenance and it acts as
      a negative regulator of telomere length. In addition to its telomeric function,
      we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics
      experiments that ZBTB48 acts as a transcriptional activator on a small set of
      target genes, including mitochondrial fission process 1 (MTFP1). This discovery
      places ZBTB48 at the interface of telomere length regulation, transcriptional
      control and mitochondrial metabolism.

PMID- 28500260
TI  - Anticoagulation therapy for thromboembolism prevention: a case of warfarin
      induced skin necrosis in the setting of protein C deficiency.
AB  - Patients with protein C deficiency are at increased risk for thrombolic diseases.
      Non-vitamin K antagonist anticoagulant options should be considered in patients
      with warfarin-induced skin necrosis (WISN) in the setting of protein C. We report
      a 41-year-old African American male patient with WISN and protein C deficiency
      who was treated with rivaroxaban followed by dabigatran. After 1 month on
      rivaroxaban, he began experiencing blood in his stools, unrelenting pain in his
      lower extremities, found it difficult to obtain medication despite having
      insurance and as a result did not maintain compliance. He was then assessed at
      the hospital, symptomatically treated and discharged on dabigatran. After 6
      weeks, he reported symptomatic relief and less side effects. This case involved a
      head-to-head clinical comparison of rivaroxaban and dabigatran as alternatives to
      warfarin anticoagulation therapy.

PMID- 28500261
TI  - Osmotic demyelination syndrome in type 1 diabetes in the absence of
      dyselectrolytaemia: an overlooked complication?
AB  - Central pontine myelinolysis (CPM) is a demyelinating disorder of central nervous
      system which involves central portion of the pons and sometimes extrapontine
      areas also. It is commonly reported in settings of hyponatraemia or its rapid
      correction, but in the last few years it has also been reported in patients with
      diabetes in the absence of electrolyte disturbances or correction of serum
      osmolality. Here we report a case of a 20-year-old female patient, with a known
      history of type 1 diabetes mellitus, who presented with acute onset spastic
      quadriparesis with dysarthria and mild ataxia which evolved over 2 weeks. Her MRI
      brain showed well-defined, bilateral symmetric hyperintense lesion involving
      central pons showing area of diffusion restriction which was consistent with CPM.
      Patient was treated conservatively and improved over a period of few weeks. To
      diagnose more number of cases, we should not overlook CPM in patients with
      diabetes.

PMID- 28500258
TI  - Transposon-driven transcription is a conserved feature of vertebrate
      spermatogenesis and transcript evolution.
AB  - Spermatogenesis is associated with major and unique changes to chromosomes and
      chromatin. Here, we sought to understand the impact of these changes on
      spermatogenic transcriptomes. We show that long terminal repeats (LTRs) of
      specific mouse endogenous retroviruses (ERVs) drive the expression of many long
      non-coding transcripts (lncRNA). This process occurs post-mitotically
      predominantly in spermatocytes and round spermatids. We demonstrate that this
      transposon-driven lncRNA expression is a conserved feature of vertebrate
      spermatogenesis. We propose that transposon promoters are a mechanism by which
      the genome can explore novel transcriptional substrates, increasing evolutionary
      plasticity and allowing for the genesis of novel coding and non-coding genes.
      Accordingly, we show that a small fraction of these novel ERV-driven transcripts
      encode short open reading frames that produce detectable peptides. Finally, we
      find that distinct ERV elements from the same subfamilies act as differentially
      activated promoters in a tissue-specific context. In summary, we demonstrate that
      LTRs can act as tissue-specific promoters and contribute to post-mitotic
      spermatogenic transcriptome diversity.

PMID- 28500262
TI  - Recurrent syncope in systemic lupus erythematosus: a hidden cause in abdomen.
AB  - Systemic inflammatory rheumatic diseases have shown an increase in frequency of
      internal malignancies, predominantly lymphoproliferative disorders. Occurrence of
      solid organ tumours is exceedingly rare. It is even rarer for it to manifest as
      recurrent syncope. We report a 55-year-old woman with systemic lupus
      erythematosus, who later developed episodes of syncope and dizziness along with
      diaphoresis and palpitations. She also had associated abdominal pain and
      vomiting. Imaging revealed a gall bladder (GB) mass with hepatic extension, which
      was histologically consistent with adenocarcinoma of the GB. Subsequently she
      succumbed to death during chemotherapy.

PMID- 28500263
TI  - Migration of eroded laparoscopic adjustable gastric band causing small bowel
      obstruction and perforation.
AB  - We present an unusual and rare complication caused by gastric band erosion into
      the stomach after band placement 15 years ago. The complication was only picked
      up after the band had subsequently migrated from the stomach at the site of
      erosion, to the distal ileum causing acute small bowel obstruction and focal
      perforation requiring emergency laparotomy.Abdominal pain in patients with
      gastric band should always be treated as serious until proven otherwise.

PMID- 28500264
TI  - S1P receptor 1-Mediated Anti-Renin-Angiotensin System Cardioprotection: Pivotal
      Role of Mast Cell Aldehyde Dehydrogenase Type 2.
AB  - In the ischemic-reperfused (I/R) heart, renin-containing mast cells (MC) release
      enzymatically active renin, activating a local renin-angiotensin system (RAS),
      causing excessive norepinephrine release and arrhythmic dysfunction. Activation
      of Gi-receptors on MC and/or ischemic preconditioning (IPC) prevent renin
      release, thus providing anti-RAS cardioprotection. We questioned whether
      sphingosine-1-phosphate (S1P), a sphingolipid produced in the I/R heart, might
      afford anti-RAS cardioprotection by activating Gi-coupled S1P1 receptors (S1P1R)
      on MC. We report that activation of Gi-coupled S1P1R in cardiac MC confers IPC
      like anti-RAS cardioprotection due to S1P1R-mediated inhibition of I/R-induced
      cardiac MC degranulation and renin release. This results from an initial
      translocation of protein kinase C subtype-epsilon and subsequent activation of
      aldehyde dehydrogenase type 2 (ALDH2), culminating in the elimination of the MC
      degranulating effects of acetaldehyde and other toxic species produced during
      I/R. Inhibition of toxic aldehydes-induced MC-renin release prevents local RAS
      activation, reduces infarct size, and alleviates arrhythmias. Notably, these
      cardioprotective effects are lacking in hearts and MC from gene-targeted knock-in
      mice (ALDH2*2) in which ALDH2 enzymatic activity is maximally reduced. Thus,
      ALDH2 appears to play a pivotal role in this protective process. Our findings
      suggest that MC S1P1R may represent a new pharmacologic and therapeutic target
      for the direct alleviation of RAS-induced cardiac dysfunctions, including
      ischemic heart disease and congestive heart failure.

PMID- 28500265
TI  - Acyl-CoA-Binding Protein ACBP1 Modulates Sterol Synthesis during Embryogenesis.
AB  - Fatty acids (FAs) and sterols are primary metabolites that exert interrelated
      functions as structural and signaling lipids. Despite their common syntheses from
      acetyl-coenzyme A, homeostatic cross talk remains enigmatic. Six Arabidopsis
      (Arabidopsis thaliana) acyl-coenzyme A-binding proteins (ACBPs) are involved in
      FA metabolism. ACBP1 interacts with PHOSPHOLIPASE Dalpha1 and regulates
      phospholipid composition. Here, its specific role in the negative modulation of
      sterol synthesis during embryogenesis is reported. ACBP1, likely in a liganded
      state, interacts with STEROL C4-METHYL OXIDASE1-1 (SMO1-1), a rate-limiting
      enzyme in the sterol pathway. Proembryo abortion in the double mutant indicated
      that the ACBP1-SMO1-1 interaction is synthetic lethal, corroborating with their
      strong promoter activities in developing ovules. Gas chromatography-mass
      spectrometry revealed quantitative and compositional changes in FAs and sterols
      upon overexpression or mutation of ACBP1 and/or SMO1-1 Aberrant levels of these
      metabolites may account for the downstream defect in lipid signaling. GLABRA2
      (GL2), encoding a phospholipid/sterol-binding homeodomain transcription factor,
      was up-regulated in developing seeds of acbp1, smo1-1, and ACBP1+/-smo1-1 in
      comparison with the wild type. Consistent with the corresponding transcriptional
      alteration of GL2 targets, high-oil, low-mucilage phenotypes of gl2 were
      phenocopied in ACBP1+/-smo1-1 Thus, ACBP1 appears to modulate the metabolism of
      two important lipid classes (FAs and sterols) influencing cellular signaling.

PMID- 28500266
TI  - NADPH Thioredoxin Reductase C and Thioredoxins Act Concertedly in Seedling
      Development.
AB  - Thiol-dependent redox regulation of enzyme activity plays a central role in the
      rapid acclimation of chloroplast metabolism to ever-fluctuating light
      availability. This regulatory mechanism relies on ferredoxin reduced by the
      photosynthetic electron transport chain, which fuels reducing power to
      thioredoxins (Trxs) via a ferredoxin-dependent Trx reductase. In addition,
      chloroplasts harbor an NADPH-dependent Trx reductase, which has a joint Trx
      domain at the carboxyl terminus, termed NTRC. Thus, a relevant issue concerning
      chloroplast function is to establish the relationship between these two redox
      systems and its impact on plant development. To address this issue, we generated
      Arabidopsis (Arabidopsis thaliana) mutants combining the deficiency of NTRC with
      those of Trxs f, which participate in metabolic redox regulation, and that of Trx
      x, which has antioxidant function. The ntrc-trxf1f2 and, to a lower extent, ntrc
      trxx mutants showed severe growth-retarded phenotypes, decreased photosynthesis
      performance, and almost abolished light-dependent reduction of fructose-1,6
      bisphosphatase. Moreover, the combined deficiency of both redox systems provokes
      aberrant chloroplast ultrastructure. Remarkably, both the ntrc-trxf1f2 and ntrc
      trxx mutants showed high mortality at the seedling stage, which was overcome by
      the addition of an exogenous carbon source. Based on these results, we propose
      that NTRC plays a pivotal role in chloroplast redox regulation, being necessary
      for the activity of diverse Trxs with unrelated functions. The interaction
      between the two thiol redox systems is indispensable to sustain photosynthesis
      performed by cotyledons chloroplasts, which is essential for early plant
      development.

PMID- 28500267
TI  - Impaired Mitochondrial Transcription Termination Disrupts the Stromal Redox Poise
      in Chlamydomonas.
AB  - In photosynthetic eukaryotes, the metabolite exchange between chloroplast and
      mitochondria ensures efficient photosynthesis under saturating light conditions.
      The Chlamydomonas reinhardtii mutant stm6 is devoid of the mitochondrial
      transcription termination factor MOC1 and aberrantly expresses the mitochondrial
      genome, resulting in enhanced photosynthetic hydrogen production and diminished
      light tolerance. We analyzed the modulation of mitochondrial and
      chlororespiration during the acclimation of stm6 and the MOC1-complemented strain
      to excess light. Although light stress stimulated mitochondrial respiration via
      the energy-conserving cytochrome c pathway in both strains, the mutant was unable
      to fine-tune the expression and activity of oxidative phosphorylation complex I
      in excess light, which was accompanied by an increased mitochondrial respiration
      via the alternative oxidase pathway. Furthermore, stm6 failed to fully activate
      chlororespiration and cyclic electron flow due to a more oxidized state of the
      chloroplast stroma, which is caused by an increased mitochondrial electron sink
      capacity. Increased susceptibility to photoinhibition of PSII in stm6
      demonstrates that the MOC1-dependent modulation of mitochondrial respiration
      helps control the stromal redox poise as a crucial part of high-light acclimation
      in C. reinhardtii.

PMID- 28500269
TI  - Dynamic Cytology and Transcriptional Regulation of Rice Lamina Joint Development.
AB  - Rice (Oryza sativa) leaf angle is determined by lamina joint and is an important
      agricultural trait determining leaf erectness and, hence, the photosynthesis
      efficiency and grain yield. Genetic studies reveal a complex regulatory network
      of lamina joint development; however, the morphological changes, cytological
      transitions, and underlying transcriptional programming remain to be elucidated.
      A systemic morphological and cytological study reveals a dynamic developmental
      process and suggests a common but distinct regulation of the lamina joint.
      Successive and sequential cell division and expansion, cell wall thickening, and
      programmed cell death at the adaxial or abaxial sides form the cytological basis
      of the lamina joint, and the increased leaf angle results from the asymmetric
      cell proliferation and elongation. Analysis of the gene expression profiles at
      four distinct developmental stages ranging from initiation to senescence showed
      that genes related to cell division and growth, hormone synthesis and signaling,
      transcription (transcription factors), and protein phosphorylation (protein
      kinases) exhibit distinct spatiotemporal patterns during lamina joint
      development. Phytohormones play crucial roles by promoting cell differentiation
      and growth at early stages or regulating the maturation and senescence at later
      stages, which is consistent with the quantitative analysis of hormones at
      different stages. Further comparison with the gene expression profile of leaf
      inclination1, a mutant with decreased auxin and increased leaf angle, indicates
      the coordinated effects of hormones in regulating lamina joint. These results
      reveal a dynamic cytology of rice lamina joint that is fine-regulated by multiple
      factors, providing informative clues for illustrating the regulatory mechanisms
      of leaf angle and plant architecture.

PMID- 28500268
TI  - A Rice NAC Transcription Factor Promotes Leaf Senescence via ABA Biosynthesis.
AB  - It is well known that abscisic acid (ABA)-induced leaf senescence and premature
      leaf senescence negatively affect the yield of rice (Oryza sativa). However, the
      molecular mechanism underlying this relationship, especially the upstream
      transcriptional network that modulates ABA level during leaf senescence, remains
      largely unknown. Here, we demonstrate a rice NAC transcription factor, OsNAC2,
      that participates in ABA-induced leaf senescence. Overexpression of OsNAC2
      dramatically accelerated leaf senescence, whereas its knockdown lines showed a
      delay in leaf senescence. Chromatin immunoprecipitation-quantitative PCR, dual
      luciferase, and yeast one-hybrid assays demonstrated that OsNAC2 directly
      activates expression of chlorophyll degradation genes, OsSGR and OsNYC3 Moreover,
      ectopic expression of OsNAC2 leads to an increase in ABA levels via directly up
      regulating expression of ABA biosynthetic genes (OsNCED3 and OsZEP1) as well as
      down-regulating the ABA catabolic gene (OsABA8ox1). Interestingly, OsNAC2 is
      upregulated by a lower level of ABA but downregulated by a higher level of ABA,
      indicating a feedback repression of OsNAC2 by ABA. Additionally, reduced OsNAC2
      expression leads to about 10% increase in the grain yield of RNAi lines. The
      novel ABA-NAC-SAGs regulatory module might provide a new insight into the
      molecular action of ABA to enhance leaf senescence and elucidates the
      transcriptional network of ABA production during leaf senescence in rice.

PMID- 28500270
TI  - Heavy Metals Induce Iron Deficiency Responses at Different Hierarchic and
      Regulatory Levels.
AB  - In plants, the excess of several heavy metals mimics iron (Fe) deficiency-induced
      chlorosis, indicating a disturbance in Fe homeostasis. To examine the level at
      which heavy metals interfere with Fe deficiency responses, we carried out an in
      depth characterization of Fe-related physiological, regulatory, and morphological
      responses in Arabidopsis (Arabidopsis thaliana) exposed to heavy metals. Enhanced
      zinc (Zn) uptake closely mimicked Fe deficiency by leading to low chlorophyll but
      high ferric-chelate reductase activity and coumarin release. These responses were
      not caused by Zn-inhibited Fe uptake via IRON-REGULATED TRANSPORTER (IRT1).
      Instead, Zn simulated the transcriptional response of typical Fe-regulated genes,
      indicating that Zn affects Fe homeostasis at the level of Fe sensing. Excess
      supplies of cobalt and nickel altered root traits in a different way from Fe
      deficiency, inducing only transient Fe deficiency responses, which were
      characterized by a lack of induction of the ethylene pathway. Cadmium showed a
      rather inconsistent influence on Fe deficiency responses at multiple levels. By
      contrast, manganese evoked weak Fe deficiency responses in wild-type plants but
      strongly exacerbated chlorosis in irt1 plants, indicating that manganese
      antagonized Fe mainly at the level of transport. These results show that the
      investigated heavy metals modulate Fe deficiency responses at different
      hierarchic and regulatory levels and that the interaction of metals with
      physiological and morphological Fe deficiency responses is uncoupled. Thus, this
      study not only emphasizes the importance of assessing heavy metal toxicities at
      multiple levels but also provides a new perspective on how Fe deficiency
      contributes to the toxic action of individual heavy metals.

PMID- 28500271
TI  - Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart
      Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization
      Analysis.
AB  - BACKGROUND: The implications of different adiposity measures on cardiovascular
      disease etiology remain unclear. In this article, we quantify and contrast causal
      associations of central adiposity (waist-to-hip ratio adjusted for body mass
      index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with
      cardiometabolic disease. METHODS: Ninety-seven independent single-nucleotide
      polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were
      used to conduct Mendelian randomization analyses in 14 prospective studies
      supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D
      (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM]
      plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases),
      stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus
      from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and
      lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants)
      consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke
      subtypes; secondary analyses included 18 cardiometabolic traits. RESULTS: Each
      one standard deviation (SD) higher WHRadjBMI (1 SD~0.08 U) associated with a 48%
      excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI],
      1.28-1.71), similar to findings for BMI (1 SD~4.6 kg/m2; OR for CHD, 1.36; 95%
      CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95%
      CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects:
      OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher
      WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with
      higher left ventricular hypertrophy, glycemic traits, interleukin 6, and
      circulating lipids. WHRadjBMI was also associated with higher carotid intima
      media thickness (39%; 95% CI, 9%-77% per 1 SD). CONCLUSIONS: Both general and
      central adiposity have causal effects on CHD and type 2 diabetes mellitus.
      Central adiposity may have a stronger effect on stroke risk. Future estimates of
      the burden of adiposity on health should include measures of central and general
      adiposity.

PMID- 28500273
TI  - Fundamental trade-offs between information flow in single cells and cellular
      populations.
AB  - Signal transduction networks allow eukaryotic cells to make decisions based on
      information about intracellular state and the environment. Biochemical noise
      significantly diminishes the fidelity of signaling: networks examined to date
      seem to transmit less than 1 bit of information. It is unclear how networks that
      control critical cell-fate decisions (e.g., cell division and apoptosis) can
      function with such low levels of information transfer. Here, we use theory,
      experiments, and numerical analysis to demonstrate an inherent trade-off between
      the information transferred in individual cells and the information available to
      control population-level responses. Noise in receptor-mediated apoptosis reduces
      information transfer to approximately 1 bit at the single-cell level but allows 3
      4 bits of information to be transmitted at the population level. For processes
      such as eukaryotic chemotaxis, in which single cells are the functional unit, we
      find high levels of information transmission at a single-cell level. Thus, low
      levels of information transfer are unlikely to represent a physical limit.
      Instead, we propose that signaling networks exploit noise at the single-cell
      level to increase population-level information transfer, allowing extracellular
      ligands, whose levels are also subject to noise, to incrementally regulate
      phenotypic changes. This is particularly critical for discrete changes in fate
      (e.g., life vs. death) for which the key variable is the fraction of cells
      engaged. Our findings provide a framework for rationalizing the high levels of
      noise in metazoan signaling networks and have implications for the development of
      drugs that target these networks in the treatment of cancer and other diseases.

PMID- 28500272
TI  - Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory
      set-point for a cytoskeletal modulator in bipolar pathogenesis.
AB  - The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using
      human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in
      polygenic diseases is generally challenging. However, hiPSCs from BPD patients
      responsive to lithium offered unique opportunities to discern lithium's target
      and hence gain molecular insight into BPD. By profiling the proteomics of BDP
      hiPSC-derived neurons, we found that lithium alters the phosphorylation state of
      collapsin response mediator protein-2 (CRMP2). Active nonphosphorylated CRMP2,
      which binds cytoskeleton, is present throughout the neuron; inactive
      phosphorylated CRMP2, which dissociates from cytoskeleton, exits dendritic
      spines. CRMP2 elimination yields aberrant dendritogenesis with diminished spine
      density and lost lithium responsiveness (LiR). The "set-point" for the ratio of
      pCRMP2:CRMP2 is elevated uniquely in hiPSC-derived neurons from LiR BPD patients,
      but not with other psychiatric (including lithium-nonresponsive BPD) and
      neurological disorders. Lithium (and other pathway modulators) lowers pCRMP2,
      increasing spine area and density. Human BPD brains show similarly elevated
      ratios and diminished spine densities; lithium therapy normalizes the ratios and
      spines. Consistent with such "spine-opathies," human LiR BPD neurons with
      abnormal ratios evince abnormally steep slopes for calcium flux; lithium
      normalizes both. Behaviorally, transgenic mice that reproduce lithium's
      postulated site-of-action in dephosphorylating CRMP2 emulate LiR in BPD. These
      data suggest that the "lithium response pathway" in BPD governs CRMP2's
      phosphorylation, which regulates cytoskeletal organization, particularly in
      spines, modulating neural networks. Aberrations in the posttranslational
      regulation of this developmentally critical molecule may underlie LiR BPD
      pathogenesis. Instructively, examining the proteomic profile in hiPSCs of a
      functional agent-even one whose mechanism-of-action is unknown-might reveal
      otherwise inscrutable intracellular pathogenic pathways.

PMID- 28500277
TI  - Ba/F3 transformation assays.

PMID- 28500274
TI  - Combined HMG-COA reductase and prenylation inhibition in treatment of CCM.
AB  - Cerebral cavernous malformations (CCMs) are common vascular anomalies that
      develop in the central nervous system and, more rarely, the retina. The lesions
      can cause headache, seizures, focal neurological deficits, and hemorrhagic
      stroke. Symptomatic lesions are treated according to their presentation; however,
      targeted pharmacological therapies that improve the outcome of CCM disease are
      currently lacking. We performed a high-throughput screen to identify Food and
      Drug Administration-approved drugs or other bioactive compounds that could
      effectively suppress hyperproliferation of mouse brain primary astrocytes
      deficient for CCM3. We demonstrate that fluvastatin, an inhibitor of 3-hydroxy-3
      methyl-glutaryl (HMG)-CoA reductase and the N-bisphosphonate zoledronic acid
      monohydrate, an inhibitor of protein prenylation, act synergistically to reverse
      outcomes of CCM3 loss in cultured mouse primary astrocytes and in Drosophila
      glial cells in vivo. Further, the two drugs effectively attenuate neural and
      vascular deficits in chronic and acute mouse models of CCM3 loss in vivo,
      significantly reducing lesion burden and extending longevity. Sustained
      inhibition of the mevalonate pathway represents a potential pharmacological
      treatment option and suggests advantages of combination therapy for CCM disease.

PMID- 28500275
TI  - Experimental evaluation of the generalized vibrational theory of G protein
      coupled receptor activation.
AB  - Recently, an alternative theory concerning the method by which olfactory proteins
      are activated has garnered attention. This theory proposes that the activation of
      olfactory G protein-coupled receptors occurs by an inelastic electron tunneling
      mechanism that is mediated through the presence of an agonist with an appropriate
      vibrational state to accept the inelastic portion of the tunneling electron's
      energy. In a recent series of papers, some suggestive theoretical evidence has
      been offered that this theory may be applied to nonolfactory G protein-coupled
      receptors (GPCRs), including those associated with the central nervous system
      (CNS). [Chee HK, June OS (2013) Genomics Inform 11(4):282-288; Chee HK, et al.
      (2015) FEBS Lett 589(4):548-552; Oh SJ (2012) Genomics Inform 10(2):128-132].
      Herein, we test the viability of this idea, both by receptor affinity and
      receptor activation measured by calcium flux. This test was performed using a
      pair of well-characterized agonists for members of the 5-HT2 class of serotonin
      receptors, 2,5-dimethoxy-4-iodoamphetamine (DOI) and N,N-dimethyllysergamide (DAM
      57), and their respective deuterated isotopologues. No evidence was found that
      selective deuteration affected either the binding affinity or the activation by
      the selected ligands for the examined members of the 5-HT2 receptor class.

PMID- 28500278
TI  - Comparison of Echocardiography and 64-Multislice Spiral Computed Tomography for
      the Diagnosis of Pediatric Congenital Heart Disease.
AB  - BACKGROUND The goals of this study were: to compare echocardiogram and 64
      multislice spiral computed tomography (64-MSCT) in diagnosing pediatric
      congenital heart disease; to determine the significance of ECHO for diagnosing
      congenital heart disease; and to identify the appropriate diagnosis for
      congenital heart disease through combined use of 64-MSCT and ECHO. MATERIAL AND
      METHODS Thirty patients underwent both ECHO and 64-MSCT diagnoses before their
      surgeries. Imaging from ECHO and 64-MSCT were analyzed by 4 specialists. The
      diagnostic accuracy and kappa value of ECHO and 64-MSCT were evaluated based on
      the operation results. The accuracy of the 2 methods was evaluated using the
      McNemar chi2 test. RESULTS We confirmed 138 malformations in 30 children by
      surgery. The diagnostic accuracy of ECHO and 64-MSCT was 98.40% and 96.20%,
      respectively, with a significant difference between the 2 results (chi2=6.404,
      P=0.011). We compared prognosis accuracy and uniformity on 3 types of congenital
      heart disease (cardiac malformation, heart-large vascular connecting
      malformation, and large vascular malformation): 56 cardiac malformations were
      confirmed by surgery, in which the diagnostic accuracy of ECHO and 64-MSCT was
      99.50% and 94.80%, respectively. (chi2=8.578, P=0.034); 31 heart-large vascular
      connecting malformations were confirmed by surgery, in which the diagnostic
      accuracy of ECHO and 64-MSCT was 99.00% and 95.42% (chi2=6.779, P=0.009); and 51
      vascular malformations were confirmed, in which the diagnostic accuracy of ECHO
      and 64-MSCT was 96.30% and 98.30% (chi2=1.806, P=0.179). CONCLUSIONS ECHO is more
      effective than 64-MSCT in preoperative diagnosis of congenital heart disease,
      especially for children.

PMID- 28500279
TI  - New Navigation Surgery for Resection of Lymphatic Malformations Using Indocyanine
      Green Fluorescence Imaging.
AB  - BACKGROUND We used indocyanine green (ICG) fluorescence imaging to completely
      resect lymphatic malformations (LMs). This is the first report of navigation
      surgery utilizing ICG fluorescence imaging for resection of LMs. CASE REPORT A 15
      year-old boy was diagnosed with LMs in the abdominal wall. The extent of the
      tumor was determined by an ultrasound, and ICG (Diagnogreen(r), Daiichi-Sankyo
      Pharma, Tokyo, Japan) was injected subcutaneously and intradermally into the core
      and 2 marginal regions of the tumor (3 injections in total), respectively. During
      surgery, the extent of the tumor was confirmed with a photodynamic eye, and the
      tumor was completely resected. A fluorescent portion macroscopically estimated as
      normal was additionally resected and no residual fluorescence or tumor were
      confirmed in the remaining tissue. Abnormal lymphatic vessels were
      histopathologically observed in the additionally resected tissue, indicating the
      invasion of LMs. The surgery had a good outcome with no evidence of recurrence.
      CONCLUSIONS We performed near-infrared fluorescence-guided imaging surgery for
      the resection of LMs in the abdominal wall. This is a single case study;
      therefore, assessment of more cases is warranted for further validation. This
      procedure could provide significant benefit to patients requiring resection of
      LMs.

PMID- 28500280
TI  - Visualization of a Mammalian Mitochondrion by Coherent X-ray Diffractive Imaging.
AB  - We report a three dimensional (3D) quantitative visualization of a mammalian
      mitochondrion by coherent x-ray diffractive imaging (CXDI) using synchrotron
      radiation. The internal structures of a mitochondrion from a mouse embryonic
      fibroblast cell line (NIH3T3) were visualized by tomographic imaging at
      approximately 60 nm resolution without the need for sectioning or staining. The
      overall structure consisted of a high electron density region, composed of the
      outer and inner membranes and the cristae cluster, which enclosed the lower
      density mitochondrial matrix. The average mass density of the mitochondrion was
      about 1.36 g/cm3. Sectioned images of the cristae reveal that they have neither a
      baffle nor septa shape but were instead irregular. In addition, a high
      resolution, about 14 nm, 2D projection image was captured of a similar
      mitochondrion with the aid of strongly scattering Au reference objects. Obtaining
      3D images at this improved resolution will allow CXDI to be an effective and
      nondestructive method for investigating the innate structure of mitochondria and
      other important life supporting organelles.

PMID- 28500281
TI  - Layered social influence promotes multiculturality in the Axelrod model.
AB  - Despite the presence of increasing pressure towards globalisation, the
      coexistence of different cultures is a distinctive feature of human societies.
      However, how multiculturality can emerge in a population of individuals inclined
      to imitation, and how it remains stable under cultural drift, i.e. the
      spontaneous mutation of traits in the population, still needs to be understood.
      To solve such a problem, we propose here a microscopic model of culture
      dissemination which takes into account that, in real social systems, the
      interactions are organised in various layers corresponding to different interests
      or topics. We show that the addition of multiplexity in the modeling of our
      society generates qualitatively novel dynamical behavior, producing a new stable
      regime of cultural diversity. This finding suggests that the layered organisation
      of social influence typical of modern societies is the key ingredient to explain
      why and how multiculturality emerges and thrives in our world.

PMID- 28500282
TI  - The molecular basis of thin filament activation: from single molecule to muscle.
AB  - For muscles to effectively power locomotion, trillions of myosin molecules must
      rapidly attach and detach from the actin thin filament. This is accomplished by
      precise regulation of the availability of the myosin binding sites on actin (i.e.
      activation). Both calcium (Ca++) and myosin binding contribute to activation, but
      both mechanisms are simultaneously active during contraction, making their
      relative contributions difficult to determine. Further complicating the process,
      myosin binding accelerates the attachment rate of neighboring myosin molecules,
      adding a cooperative element to the activation process. To de-convolve these two
      effects, we directly determined the effect of Ca++ on the rate of attachment of a
      single myosin molecule to a single regulated actin thin filament, and separately
      determined the distance over which myosin binding increases the attachment rate
      of neighboring molecules. Ca++ alone increases myosin's attachment rate ~50-fold,
      while myosin binding accelerates attachment of neighboring molecules 400 nm along
      the actin thin filament.

PMID- 28500283
TI  - Fine-tune regulation of carboxypeptidase N1 controls vascular patterning during
      zebrafish development.
AB  - Vascular development is regulated by complicated signals and molecules in
      vertebrates. In this study, we characterized a novel function of carboxypeptidase
      N1 (Cpn1) in the vasculature. We show that cpn1 mRNA is expressed in developing
      vessels. The knockdown of cpn1 by morpholino injection impairs the growth of
      intersegmental vessels (ISV) and caudal vein plexus (CVP), suggesting the role of
      cpn1 in vascular development. We showed that vascular defects are not caused by
      cell death but are due to the impairment of migration and proliferation.
      Consistent with vascular growth defects, loss of cpn1 affects the expression of
      the vascular markers flt4, mrc1, flk, stabilin, and ephrinb2. Furthermore, the
      overexpression of cpn1 impaired the growth of ISV and CVP, but the remodeling
      expression of vascular markers was different from the knockdown of cpn1,
      indicating the differential regulation mechanisms in cpn1-overexpressing embryos.
      We examine the interaction between cpn1 and multiple signals and observed that
      cpn1 is regulated by Notch/VEGF signals for ISV growth and likely regulates BMP
      signals for CVP patterning. In conclusion, we demonstrate that cpn1 has a
      critical role in the vascular development of zebrafish. We also reveal a fine
      tune regulation of cpn1 that controls vascular patterning mediated by multiple
      signals.

PMID- 28500284
TI  - Hotspot analyses indicate significant conservation gaps for evergreen broadleaved
      woody plants in China.
AB  - Evergreen broadleaved woody plants (EBWPs) are dominant components in forests and
      savanna of the global tropic and subtropic regions. Southern China possesses the
      largest continuous area of subtropical EBWPs distribution, harboring a high
      proportion of endemic species. Hotspot and gap analyses are effective methods for
      analyzing the spatial pattern of biodiversity and conservation and were used here
      for EBWPs in China. Based on a distribution data set of 6,265 EBWPs with a
      spatial resolution of 50 * 50 km, we measured diversity of EBWPs in China using
      four indices: species richness, corrected weighted endemism, relative
      phylogenetic diversity, and phylogenetic endemism. According to the results based
      on 10% threshold, 15.73% of China's land area was identified as hotspots using at
      least one diversity index. Only 2.14% of China's land area was identified as
      hotspots for EBWPs by all four metrics simultaneously. Most of the hotspots
      locate in southern mountains. Moreover, we found substantial conservation gaps
      for Chinese EBWPs. Only 25.43% of the hotspots are covered by existing nature
      reserves by more than 10% of their area. We suggest to promote the establishment
      and management of nature reserve system within the hotspot gaps.

PMID- 28500285
TI  - Topological Quantum Phase Transition and Local Topological Order in a Strongly
      Interacting Light-Matter System.
AB  - An attempt is made to understand the topological quantum phase transition,
      emergence of relativistic modes and local topological order of light in a
      strongly interacting light-matter system. We study this system, in a one
      dimensional array of nonlinear cavities. Topological quantum phase transition
      occurs with massless excitation only for the finite detuning process. We present
      a few results based on the exact analytical calculations along with the physical
      explanations. We observe the emergence of massive Majorana fermion mode at the
      topological state, massless Majorana-Weyl fermion mode during the topological
      quantum phase transition and Dirac fermion mode for the non-topological state.
      Finally, we study the quantized Berry phase (topological order) and its
      connection to the topological number (winding number).

PMID- 28500288
TI  - Light perception in aerial tissues enhances DWF4 accumulation in root tips and
      induces root growth.
AB  - Many attempts have been made to characterize the activities of brassinosteroids
      (BRs), which are important plant hormones. The crosstalk between light perception
      and the BR signalling pathway has been extensively studied regarding its effects
      on photomorphogenesis, especially in elongating etiolated hypocotyls. In
      contrast, how and where the light induces BR biosynthesis remain uncharacterized.
      DWF4 is one of the main enzymes involved in the BR biosynthesis pathway in
      Arabidopsis thaliana. We established DWF4-GUS A. thaliana lines in a homozygous
      dwf4-102 genetic background, but functionally complemented with a genomic DWF4
      sequence fused in-frame with a beta-glucuronidase (GUS) marker gene. The DWF4-GUS
      plants enabled the visualization of the accumulation of DWF4 under different
      conditions. We investigated the effects of aboveground light on root and
      hypocotyl growth. We observed that root length increased when shoots were
      maintained under light irrespective of whether roots were exposed to light. We
      also determined that light perception in aerial tissues enhanced DWF4
      accumulation in the root tips. Overall, our data indicate that BR biosynthesis is
      promoted in the root tip regions by an unknown mechanism in distantly located
      shoot tissues exposed to light, leading to increased root growth.

PMID- 28500287
TI  - Determination of nasal and oropharyngeal microbiomes in a multicenter population
      based study - findings from Pretest 1 of the German National Cohort.
AB  - We examined acceptability, preference and feasibility of collecting nasal and
      oropharyngeal swabs, followed by microbiome analysis, in a population-based study
      with 524 participants. Anterior nasal and oropharyngeal swabs were collected by
      certified personnel. In addition, participants self-collected nasal swabs at home
      four weeks later. Four swab types were compared regarding (1) participants'
      satisfaction and acceptance and (2) detection of microbial community structures
      based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All
      swabbing methods were highly accepted. Microbial community structure analysis
      revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to
      nares. The calcium alginate tipped swab was found unsuitable for microbiome
      determinations. Among the remaining three swab types, there were no differences
      in oropharyngeal microbiomes detected and only marginal differences in nasal
      microbiomes. Microbial community structures did not differ between staff
      collected and self-collected nasal swabs. These results suggest (1) that nasal
      and oropharyngeal swabbing are highly feasible methods for human population-based
      studies that include the characterization of microbial community structures in
      these important ecological niches, and (2) that self-collection of nasal swabs at
      home can be used to reduce cost and resources needed, particularly when serial
      measurements are to be taken.

PMID- 28500286
TI  - A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1
      Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation.
AB  - Mechanical pain serves as a base clinical symptom for many of the world's most
      debilitating syndromes. Ion channels expressed by peripheral sensory neurons
      largely contribute to mechanical hypersensitivity. Transient Receptor Potential A
      1 (TRPA1) is a ligand-gated ion channel that contributes to inflammatory
      mechanical hypersensitivity, yet little is known as to the post-translational
      mechanism behind its somatosensitization. Here, we utilize biochemical,
      electrophysiological, and behavioral measures to demonstrate that metabotropic
      glutamate receptor-induced sensitization of TRPA1 nociceptors stimulates targeted
      modification of the receptor. Type 1 mGluR5 activation increases TRPA1 receptor
      agonist sensitivity in an AKA-dependent manner. As a scaffolding protein for
      Protein Kinases A and C (PKA and PKC, respectively), AKAP facilitates
      phosphorylation and sensitization of TRPA1 in ex vivo sensory neuronal
      preparations. Furthermore, hyperalgesic priming of mechanical hypersensitivity
      requires both TRPA1 and AKAP. Collectively, these results identify a novel AKAP
      mediated biochemical mechanism that increases TRPA1 sensitivity in peripheral
      sensory neurons, and likely contributes to persistent mechanical
      hypersensitivity.

PMID- 28500289
TI  - Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast
      cancer therapeutics.
AB  - Estradiol (E2) and the oestrogen receptor-alpha (ERalpha) signalling pathway play
      pivotal roles in the proliferative activity of breast cancer cells. Recent
      findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein
      3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERalpha signalling
      modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2
      interaction using the ERalpha activity-regulator synthetic peptide (ERAP: 165-177
      amino acids), derived from alpha-helical BIG3 sequence, resulted in a significant
      anti-tumour effect. However, the duration of this effect was very short for
      viable clinical application. We developed the chemically modified ERAP using
      stapling methods (stapledERAP) to improve the duration of its antitumour effects.
      The stapledERAP specifically inhibited the BIG3-PHB2 interaction and exhibited
      long-lasting suppressive activity. Its intracellular localization without the
      membrane-permeable polyarginine sequence was possible via the formation of a
      stable alpha-helix structure by stapling. Tumour bearing-mice treated daily or
      weekly with stapledERAP effectively prevented the BIG3-PHB2 interaction, leading
      to complete regression of E2-dependent tumours in vivo. Most importantly,
      combination of stapledERAP with tamoxifen, fulvestrant, and everolimus caused
      synergistic inhibitory effects on growth of breast cancer cells. Our findings
      suggested that the stapled ERAP may be a promising anti-tumour drug to suppress
      luminal-type breast cancer growth.

PMID- 28500290
TI  - Impact of Hepatitis C Treatment as Prevention for People Who Inject Drugs is
      sensitive to contact network structure.
AB  - Treatment as Prevention (TasP) using directly-acting antivirals has been
      advocated for Hepatitis C Virus (HCV) in people who inject drugs (PWID), but
      treatment is expensive and TasP's effectiveness is uncertain. Previous modelling
      has assumed a homogeneously-mixed population or a static network lacking turnover
      in the population and injecting partnerships. We developed a transmission-dynamic
      model on a dynamic network of injecting partnerships using data from survey of
      injecting behaviour carried out in London, UK. We studied transmission on a novel
      exponential-clustered network, as well as on two simpler networks for comparison,
      an exponential unclustered and a random network, and found that TasP's
      effectiveness differs markedly. With respect to an exponential-clustered network,
      the random network (and homogeneously-mixed population) overestimate TasP's
      effectiveness, whereas the exponential-unclustered network underestimates it. For
      all network types TasP's effectiveness depends on whether treated patients change
      risk behaviour, and on treatment coverage: higher coverage requires fewer total
      treatments for the same health gain. Whilst TasP can greatly reduce HCV
      prevalence, incidence of infection, and incidence of reinfection in PWID,
      assessment of TasP's effectiveness needs to take account of the injecting
      partnership network structure and post-treatment behaviour change, and further
      empirical study is required.

PMID- 28500291
TI  - The complete chloroplast genome sequence of tung tree (Vernicia fordii):
      Organization and phylogenetic relationships with other angiosperms.
AB  - Tung tree (Vernicia fordii) is an economically important tree widely cultivated
      for industrial oil production in China. To better understand the molecular basis
      of tung tree chloroplasts, we sequenced and characterized its genome using PacBio
      RS II sequencing platforms. The chloroplast genome was sequenced with 161,528 bp
      in length, composed with one pair of inverted repeats (IRs) of 26,819 bp, which
      were separated by one small single copy (SSC; 18,758 bp) and one large single
      copy (LSC; 89,132 bp). The genome contains 114 genes, coding for 81 protein, four
      ribosomal RNAs and 29 transfer RNAs. An expansion with integration of an
      additional rps19 gene in the IR regions was identified. Compared to the
      chloroplast genome of Jatropha curcas, a species from the same family, the tung
      tree chloroplast genome is distinct with 85 single nucleotide polymorphisms
      (SNPs) and 82 indels. Phylogenetic analysis suggests that V. fordii is a sister
      species with J. curcas within the Eurosids I. The nucleotide sequence provides
      vital molecular information for understanding the biology of this important oil
      tree.

PMID- 28500292
TI  - Fitness estimates from experimental infections predict the long-term strain
      structure of a vector-borne pathogen in the field.
AB  - The populations of many pathogen species consist of a collection of common and
      rare strains but the factors underlying this strain-specific variation in
      frequency are often unknown. Understanding frequency variation among strains is
      particularly challenging for vector-borne pathogens where the strain-specific
      fitness depends on the performance in both the vertebrate host and the arthropod
      vector. Two sympatric multiple-strain tick-borne pathogens, Borrelia afzelii and
      B. garinii, that use the same tick vector, Ixodes ricinus, but different
      vertebrate hosts were studied. 454-sequencing of the polymorphic ospC gene was
      used to characterize the community of Borrelia strains in a local population of
      I. ricinus ticks over a period of 11 years. Estimates of the reproduction number
      (R0), a measure of fitness, were obtained for six strains of B. afzelii from a
      previous laboratory study. There was substantial variation in prevalence among
      strains and some strains were consistently common whereas other strains were
      consistently rare. In B. afzelii, the strain-specific estimates of R0 in
      laboratory mice explained over 70% of the variation in the prevalences of the
      strains in our local population of ticks. Our study shows that laboratory
      estimates of fitness can predict the community structure of multiple-strain
      pathogens in the field.

PMID- 28500293
TI  - Preparation of Nanowire like WSe2-Graphene Nanocomposite for Photocatalytic
      Reduction of CO2 into CH3OH with the Presence of Sacrificial Agents.
AB  - A nanowire-like WSe2-graphene catalyst was prepared via ultra-sonication and was
      tested in terms of the photocatalytic reduction of CO2 into CH3OH under
      irradiation with UV/visible light. The prepared nano-composite was further
      characterized via XRD, SEM, TEM, Raman and XPS. The photocurrent analysis was
      further tested for its photocatalytic reduction of CO2 using gas chromatography
      (GCMS-QP2010 SE). To further improve the the photo-catalytic efficiency, a
      sacrificial agent (Na2S/Na2SO3) was added to the WSe2-graphene nanocomposite and
      was found to improve the photo-catalytic efficiency, with the methanol yield
      reaching 5.0278 umol g-1h-1. Our present work provides a convenient way to
      prepare nanomaterials various morphologies that have future applications for
      environmental remediation.

PMID- 28500294
TI  - Adipocyte Fatty-Acid Binding Protein is Overexpressed in Cirrhosis and Correlates
      with Clinical Outcomes.
AB  - Fatty-acid-binding proteins (FABPs) are small intracellular proteins that
      coordinate lipid-mediated processes by targeting metabolic and immune response
      pathways. The aim of the study was to investigate plasma FABPs levels and their
      relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver
      and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were
      measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of
      FABPs was assessed in liver biopsies from patients with decompensated cirrhosis
      and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4
      in human liver biopsy was also performed. Plasma levels of FABPs were increased
      in patients with decompensated cirrhosis compared to those of healthy subjects (L
      FABP1: 25 (17-39) vs 10 (9-17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5-2.1) vs 0.6
      (0.4-1) ng/mL p = 0.04 and A-FABP4: 37 (20-68) vs 16 (11-33) ng/mL p = 0.002),
      respectively. Increased A-FABP4 levels were associated with complications of
      cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene
      expression was upregulated in decompensated cirrhosis. Macrophages were the main
      liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A
      FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4
      levels are increased in decompensated cirrhosis and correlate with poor outcomes.
      Liver macrophages appear to be the main source of A-FABP4 in decompensated
      cirrhosis.

PMID- 28500297
TI  - Three-dimensional quantitative fracture analysis of tight gas sandstones using
      industrial computed tomography.
AB  - Tight gas sandstone samples are imaged at high resolution industrial X-ray
      computed tomography (ICT) systems to provide a three-dimensional quantitative
      characterization of the fracture geometries. Fracture networks are quantitatively
      analyzed using a combination of 2-D slice analysis and 3-D visualization and
      counting. The core samples are firstly scanned to produce grayscale slices, and
      the corresponding fracture area, length, aperture and fracture porosity as well
      as fracture density were measured. Then the 2-D slices were stacked to create a
      complete 3-D image using volume-rendering software. The open fractures (vug) are
      colored cyan whereas the calcite-filled fractures (high density objects) are
      colored magenta. The surface area and volume of both open fractures and high
      density fractures are calculated by 3-D counting. Then the fracture porosity and
      fracture aperture are estimated by 3-D counting. The fracture porosity and
      aperture from ICT analysis performed at atmospheric pressure are higher than
      those calculated from image logs at reservoir conditions. At last, the fracture
      connectivity is determined through comparison of fracture parameters with
      permeability. Distribution of fracture density and fracture aperture determines
      the permeability and producibility of tight gas sandstones. ICT has the advantage
      of performing three dimensional fracture imaging in a non-destructive way.

PMID- 28500296
TI  - Digital Etch Technique for Forming Ultra-Scaled Germanium-Tin (Ge 1-x Sn x ) Fin
      Structure.
AB  - We developed a new digital etch process that allows precise etching of Germanium
      or Germanium-tin (Ge1-x Sn x ) materials. The digital etch approach consists of
      Ge1-x Sn x oxide formation by plasma oxidation and oxide removal in diluted
      hydrochloric acid at room temperature. The first step is a self-limiting process,
      as the thickness of oxide layer grows logarithmically with the oxidation time and
      saturates fast. Consistent etch rates in each cycle were found on the Ge1-x Sn x
      samples, with the surfaces remaining smooth after etch. The digital etch process
      parameters were tuned to achieve various etch rates. By reducing the radio
      frequency power to 70 W, etch rate of sub-1.2 nm was obtained on a Ge0.875Sn0.125
      sample. The digital etch process was employed to fabricate the Ge1-x Sn x fin
      structures. Extremely scaled Ge0.95Sn0.05 fins with 5 nm fin width were realized.
      The side walls of the Ge0.95Sn0.05 fins are smooth, and no crystal damage can be
      observed. This technique provides an option to realize aggressively scaled
      nanostructure devices based on Ge1-x Sn x materials with high-precision control.

PMID- 28500295
TI  - Angiotensin II type 1/adenosine A 2A receptor oligomers: a novel target for
      tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is a serious motor side effect that may appear after long
      term treatment with neuroleptics and mostly mediated by dopamine D2 receptors
      (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A
      receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor
      heteromers. Here, we examined whether A2AR and AT1R may oligomerize in the
      striatum to synergistically modulate dopaminergic transmission. First, by using
      bioluminescence resonance energy transfer, we demonstrated a physical AT1R-A2AR
      interaction in cultured cells. Interestingly, by protein-protein docking and
      molecular dynamics simulations, we described that a stable heterotetrameric
      interaction may exist between AT1R and A2AR bound to antagonists (i.e. losartan
      and istradefylline, respectively). Accordingly, we subsequently ascertained the
      existence of AT1R/A2AR heteromers in the striatum by proximity ligation in situ
      assay. Finally, we took advantage of a TD animal model, namely the reserpine
      induced vacuous chewing movement (VCM), to evaluate a novel multimodal
      pharmacological TD treatment approach based on targeting the AT1R/A2AR complex.
      Thus, reserpinized mice were co-treated with sub-effective losartan and
      istradefylline doses, which prompted a synergistic reduction in VCM. Overall, our
      results demonstrated the existence of striatal AT1R/A2AR oligomers with potential
      usefulness for the therapeutic management of TD.

PMID- 28500298
TI  - ZBP1 phosphorylation at serine 181 regulates its dendritic transport and the
      development of dendritic trees of hippocampal neurons.
AB  - Local protein synthesis occurs in axons and dendrites of neurons, enabling fast
      and spatially restricted responses to a dynamically changing extracellular
      environment. Prior to local translation, mRNA that is to be translated is packed
      into ribonucleoprotein particles (RNPs) where RNA binding proteins ensure mRNA
      silencing and provide a link to molecular motors. ZBP1 is a component of RNP
      transport particles and is known for its role in the local translation of beta
      actin mRNA. Its binding to mRNA is regulated by tyrosine 396 phosphorylation, and
      this particular modification was shown to be vital for axonal growth and
      dendritic branching. Recently, additional phosphorylation of ZBP1 at serine 181
      (Ser181) was described in non-neuronal cells. In the present study, we found that
      ZBP1 is also phosphorylated at Ser181 in neurons in a mammalian/mechanistic
      target of rapamycin complex 2-, Src kinase-, and mRNA binding-dependent manner.
      Furthermore, Ser181 ZBP1 phosphorylation was essential for the proper dendritic
      branching of hippocampal neurons that were cultured in vitro and for the proper
      ZBP1 dendritic distribution and motility.

PMID- 28500299
TI  - Visual processing mode switching regulated by VIP cells.
AB  - The responses of neurons in mouse primary visual cortex (V1) to visual stimuli
      depend on behavioral states. Specifically, surround suppression is reduced during
      locomotion. Although locomotion-induced vasoactive intestinal polypeptide
      positive (VIP) interneuron depolarization can account for the reduction of
      surround suppression, the functions of VIP cell depolarization are not fully
      understood. Here we utilize a firing rate model and a computational model to
      elucidate the potential functions of VIP cell depolarization during locomotion.
      Our analyses suggest 1) that surround suppression sharpens the visual responses
      in V1 to a stationary scene, 2) that depolarized VIP cells enhance V1 responses
      to moving objects by reducing self-induced surround suppression and 3) that
      during locomotion V1 neuron responses to some features of the moving objects can
      be selectively enhanced. Thus, VIP cells regulate surround suppression to allow
      pyramidal neurons to optimally encode visual information independent of
      behavioral state.

PMID- 28500300
TI  - Alterations of cerebral perfusion in asymptomatic internal carotid artery steno
      occlusive disease.
AB  - Patients with asymptomatic occlusion in the internal carotid arteries (ICA) have
      been shown to have a better preserved hemodynamic status of the brain as compared
      to patients with symptoms. This study was aimed to explore the cerebral perfusion
      alterations in asymptomatic patients using multi-parametric arterial spin
      labeling (ASL) magnetic resonance (MR) imaging. Forty-two patients diagnosed with
      asymptomatic ICA stenosis/occlusion were prospectively included and divided into
      high-grade (ultrasonographic stenosis >=70%, N = 20) and low-grade groups (N =
      22). On a 3-Tesla clinical MR scanner, pseudo-continuous ASL was performed to
      measure cerebral blood flow CBF, arterial transit time ATT, and flow territory.
      Fisher's exact test indicates that the high-grade group has higher frequency in
      asymmetric ATT (p < 10-3) and asymmetric flow territory (p < 10-3) as compared to
      the low-grade group. The between-group difference in CBF asymmetry is marginal (p
      = 0.062). Logistic regression further reveals that hemispherical asymmetry in ATT
      and flow territory is associated with the existence of high-grade ICA stenosis
      (odds ratio = 12 and 21, respectively), whereas hemispherical asymmetry in CBF is
      not. Our data suggest that ATT and flow territory may be better predictors of
      asymptomatic high-grade ICA stenosis diagnosed by carotid ultrasonography than
      CBF.

PMID- 28500301
TI  - Characterization of prophages of Lactococcus garvieae.
AB  - This report describes the morphological characterization and genome analysis of
      an induced prophage (PLg-TB25) from a dairy strain of Lactococcus garvieae. The
      phage belongs to the Siphoviridae family and its morphology is typical of other
      lactococcal phages. A general analysis of its genome did not reveal similarities
      with other lactococcal phage genomes, confirming its novelty. However,
      similarities were found between genes of its morphogenesis cluster and genes of
      Gram-positive bacteria, suggesting that this phage genome resulted from
      recombination events that took place in a heterogeneous microbial environment. An
      in silico search for other prophages in 16 L. garvieae genomes available in
      public databases, uncovered eight seemingly complete prophages in strains
      isolated from dairy and fish niches. Genome analyses of these prophages revealed
      three novel L. garvieae phages. The remaining prophages had homology to phages of
      Lactococcus lactis (P335 group) suggesting a close relationship between these
      lactococcal species. The similarity in GC content of L. garvieae prophages to the
      genomes of L. lactis phages further supports the hypothesis that these phages
      likely originated from the same ancestor.

PMID- 28500303
TI  - Photonic crystal and quasi-crystals providing simultaneous light coupling and
      beam splitting within a low refractive-index slab waveguide.
AB  - Coupling between free space components and slab waveguides is a common
      requirement for integrated optical devices, and is typically achieved by end-fire
      or grating coupling. Power splitting and distribution requires additional
      components. Usually grating couplers are used in combination with MMI/Y-splitters
      to do this task. In this paper, we present a photonic crystal device which
      performs both tasks simultaneously and is able to couple light at normal
      incidence and near normal incidence. Our approach is scalable to large channel
      counts with little impact on device footprint. We demonstrate in normal incidence
      coupling with multi-channel splitting for 785 nm light. Photonic crystals are
      etched into single mode low refractive index SiON film on both SiO2/Si and
      borosilicate glass substrate. Triangular lattices are shown to provide coupling
      to 6 beams with equal included angle (60 degrees ), while a quasi-crystal lattice
      with 12-fold rotational symmetry yields coupling to 12 beams with equal included
      angle (30 degrees ). We show how to optimize the lattice constant to achieve
      efficient phase matching between incident and coupled mode wave vectors, and how
      to adjust operating wavelength from visible to infrared wavelengths.

PMID- 28500302
TI  - Different Polyubiquitinated Bodies in Human Dendritic Cells: IL-4 Causes PaCS
      During Differentiation while LPS or IFNalpha Induces DALIS During Maturation.
AB  - Two types of polyubiquitin-reactive cytoplasmic bodies, particulate cytoplasmic
      structures (PaCS) and dendritic cell (DC) aggresome-like induced structures
      (DALIS), were analyzed by electron microscopy, immunocytochemistry,
      immunoblotting, and flow cytometry in DC obtained from human blood monocytes
      incubated with GM-CSF plus IL-4 (IL4-DC), GM-CSF plus IFNalpha (IFN-DC), or GM
      CSF alone (GM-DC), with or without LPS maturation. PaCS developed as monomorphic
      aggregates of proteasome-reactive barrel-like particles only in ribosomes-rich
      cytoplasmic areas of differentiating IL4-DC. In contrast, DALIS formed as
      vesicular bodies storing K63-linked ubiquitinated proteins by coalescence of
      increased endosomal structures, in IFN-DC or after LPS maturation of GM-DC. DALIS
      forming cells showed incomplete morphological and functional DC-type
      differentiation when compared to PaCS-forming IL4-DC. PaCS and DALIS may have
      different function as well as different origin and cytochemistry. DALIS may be a
      transient accumulation site of potentially antigenic polyubiquitinated proteins
      during their processing and presentation. PaCS are found under physiologic or
      pathologic conditions associated with increased/deranged protein synthesis and
      increased ubiquitin-proteasome activity. Given its high heat-shock protein
      content PaCS may work as a quality control structure for newly synthesized,
      cytosolic proteins. This comparative analysis suggests that PaCS and DALIS have
      distinctive roles in DC.

PMID- 28500304
TI  - Microgravity induces inhibition of osteoblastic differentiation and
      mineralization through abrogating primary cilia.
AB  - It is well documented that microgravity in space environment leads to bone loss
      in astronauts. These physiological changes have also been validated by human and
      animal studies and modeled in cell-based analogs. However, the underlying
      mechanisms are elusive. In the current study, we identified a novel phenomenon
      that primary cilia (key sensors and functioning organelles) of rat calvarial
      osteoblasts (ROBs) gradually shrank and disappeared almost completely after
      exposure to simulated microgravity generated by a random positioning machine
      (RPM). Along with the abrogation of primary cilia, the differentiation,
      maturation and mineralization of ROBs were inhibited. We also found that the
      disappearance of primary cilia was prevented by treating ROBs with cytochalasin
      D, but not with LiCl or dynein light chain Tctex-type 1 (Dynlt1) siRNA. The
      repression of the differentiation, maturation and mineralization of ROBs was
      effectively offset by cytochalasin D treatment in microgravity conditions.
      Blocking ciliogenesis using intraflagellar transport protein 88 (IFT88) siRNA
      knockdown inhibited the ability of cytochalasin D to counteract this reduction of
      osteogenesis. These results indicate that the abrogation of primary cilia may be
      responsible for the microgravity's inhibition on osteogenesis. Reconstruction of
      primary cilia may become a potential strategy against bone loss induced by
      microgravity.

PMID- 28500305
TI  - NSAIDs Use and Reduced Metastasis in Cancer Patients: results from a meta
      analysis.
AB  - This meta-analysis investigated the relationship between non-steroidal anti
      inflammatory drugs (NSAIDs) and lymph node/distant metastasis. Relevant sources
      were identified from MEDLINE, EMBASE, PubMed, and Cochrane Library. Studies that
      reported the odds ratio (OR)/risk ratio (RR)/hazard ratio (HR) with 95%
      confidence intervals (CIs) for the associations of interested outcomes were
      included. Pooled effect estimates were obtained by using random- or fixed-effect
      model depending on the heterogeneity across these studies. Sixteen studies
      involving 202780 participants, including prostate, breast, lung, and colorectal
      cancer patients, were included. Compared with the reference, generally patients
      exposed to NSAIDs at pre- and post-diagnosis experienced a significantly reduced
      risk of distant metastasis (RR 0.708, 95% CI 0.586-0.856 and RR: 0.484, 95% CI:
      0.393-0.595, respectively), including prostate cancer (pre-diagnostic use: RR =
      0.874, 95% CI, 0.787-0.97; post-diagnostic use: RR = 0.482, 95% CI 0.359-0.647),
      and breast cancer (pre-diagnostic use: RR = 0.644, 95% CI 0.565-0.735; post
      diagnostic use: RR = 0.485, 95% CI 0.362-0.651). However, lymph node metastasis
      was weakly related with pre-diagnostic use of NSAIDs (RR = 0.949, 95% CI 0.914
      0.985). NSAIDs are related to a significantly reduced risk of metastasis
      development, regardless of pre-diagnostic or post-diagnostic use. However, NSAIDs
      and lymph node metastasis are weakly associated. Our finding suggested a novel
      metastasis management.

PMID- 28500306
TI  - Plasmonic Purcell effect reveals obliquely ordered phosphorescent emitters in
      Organic LEDs.
AB  - The non-isotropic alignment of molecules can increase the interaction efficiency
      with propagating light fields. This applies to both emissive and absorptive
      systems and can be exploited for achieving unprecedented efficiencies of organic
      opto-electronic devices such as organic light-emitting diodes. Optical analysis
      has revealed certain phosphorescent emitters to align spontaneously in an
      advantageous orientation. Unfortunately, established approaches only determine an
      average orientation because emission patterns solely depend on the second moments
      of the transition dipole vector distribution. In order to resolve further details
      of such a distribution, additional differences in the emission characteristics of
      parallel and perpendicularly oriented emitters need to be introduced. A thin
      metal layer near the emitters introduces plasmon mediated losses mostly for
      perpendicular emitters. Then, analyzing the emission at different polarizations
      allows one to measure emission lifetimes of mostly parallel or mostly
      perpendicular oriented emitters. This should alter the transient emission when
      observing the temporal phosphorescence decay under different directions and/or
      polarizations. The angular width of the orientation distribution can be derived
      from the degree of such lifetime splitting. Our results suggest a narrow but
      obliquely oriented molecular ensemble of Ir(MDQ)2(acac) doped into the alpha-NPD
      host inside an Organic LED stack.

PMID- 28500307
TI  - ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged
      leukemia.
AB  - MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high
      rate of relapse and therapeutic failure due to chemotherapy resistance. In
      analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation
      (ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged
      AML, via transcription repression mediated by Polycomb repressive complex 2
      (PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays
      showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in
      vivo. Strikingly, leukemic cells with Alox5 overexpression showed a significantly
      higher sensitivity to the standard chemotherapeutic agents, i.e., doxorubicin
      (DOX) and cytarabine (Ara-C). The drug-sensitizing role of Alox5 was further
      confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as
      in the in vivo MLL-rearranged AML BMT model coupled with treatment of "5 + 3"
      (i.e. DOX plus Ara-C) regimen. Stat and K-Ras signaling pathways were negatively
      correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells; inhibition
      of the above signaling pathways mimicked the drug-sensitizing effect of ALOX5 in
      AML cells. Collectively, our work shows that ALOX5 plays a moderate anti-tumor
      role and functions as a drug sensitizer, with a therapeutic potential, in MLL
      rearranged AML.

PMID- 28500308
TI  - Ultrafast all-optical tuning of direct-gap semiconductor metasurfaces.
AB  - Optical metasurfaces are regular quasi-planar nanopatterns that can apply diverse
      spatial and spectral transformations to light waves. However, metasurfaces are no
      longer adjustable after fabrication, and a critical challenge is to realise a
      technique of tuning their optical properties that is both fast and efficient. We
      experimentally realise an ultrafast tunable metasurface consisting of
      subwavelength gallium arsenide nanoparticles supporting Mie-type resonances in
      the near infrared. Using transient reflectance spectroscopy, we demonstrate a
      picosecond-scale absolute reflectance modulation of up to 0.35 at the magnetic
      dipole resonance of the metasurfaces and a spectral shift of the resonance by 30
      nm, both achieved at unprecedentedly low pump fluences of less than 400 MUJ cm-2.
      Our findings thereby enable a versatile tool for ultrafast and efficient control
      of light using light.Metasurfaces are not adjustable after fabrication, and a
      critical challenge is to realise a technique of tuning their optical properties
      that is both fast and efficient. Here, Shcherbakov et al. realise an ultrafast
      tunable metasurface with picosecond-scale large absolute reflectance modulation
      at low pump fluences.

PMID- 28500309
TI  - Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and
      soluble endoglin and improves vascular dysfunction - implications as a
      preeclampsia treatment.
AB  - Preeclampsia is a disease of pregnancy associated with placental oxidative
      stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and
      soluble endoglin. These placental factors cause generalized maternal endothelial
      dysfunction. There are no treatments to halt disease progression; delivery is the
      only cure. Resveratrol modulates pathways involved in inflammation and oxidative
      stress and may offer a potential therapeutic for preeclampsia. Resveratrol
      reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary
      trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules
      NFkappaB, IL-6 and IL-1beta in trophoblasts. IL-6, IL-1beta and TNFalpha
      secretion were also significantly reduced. In HUVECs, resveratrol significantly
      increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not
      significantly alter HO-1 protein expression, whilst reducing HO-1 protein in
      trophoblast. Endothelial dysfunction was induced in HUVECs using TNFalpha,
      increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral
      blood mononuclear cells, both of which were increased further by resveratrol. In
      contrast, resveratrol significantly reduced TNFalpha-induced Endothelin-1 (a
      vasoconstrictor) and significantly increased the phosphorylation of endothelial
      nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti
      angiogenic factors however its effects on the endothelium are mixed. Overall, it
      may have potential as a treatment for preeclampsia.

PMID- 28500310
TI  - Bio-Inspired nacre-like nanolignocellulose-poly (vinyl alcohol)-TiO2 composite
      with superior mechanical and photocatalytic properties.
AB  - Nacre, the gold standard for biomimicry, provides an excellent example and
      guideline for assembling high-performance composites. Inspired by the layered
      structure and extraordinary strength and toughness of natural nacre, nacre-like
      nanolignocellulose/poly (vinyl alcohol)/TiO2 composites possessed the similar
      layered structure of natural nacre were constructed through hot-pressing process.
      Poly (vinyl alcohol) and TiO2 nanoparticles have been used as nanofillers to
      improve the mechanical performance and synchronously endow the superior
      photocatalytic activity of the composites. This research would be provided a
      promising candidate for the photooxidation of volatile organic compounds also
      combined with outstanding mechanical property.

PMID- 28500311
TI  - Optimisation of a Novel Spiral-Inducing Bypass Graft Using Computational Fluid
      Dynamics.
AB  - Graft failure is currently a major concern for medical practitioners in treating
      Peripheral Vascular Disease (PVD) and Coronary Artery Disease (CAD). It is now
      widely accepted that unfavourable haemodynamic conditions play an essential role
      in the formation and development of intimal hyperplasia, which is the main cause
      of graft failure. This paper uses Computational Fluid Dynamics (CFD) to conduct a
      parametric study to enhance the design and performance of a novel prosthetic
      graft, which utilises internal ridge(s) to induce spiral flow. This design is
      primarily based on the identification of the blood flow as spiral in the whole
      arterial system and is believed to improve the graft longevity and patency rates
      at distal graft anastomoses. Four different design parameters were assessed in
      this work and the trailing edge orientation of the ridge was identified as the
      most important parameter to induce physiological swirling flow, while the height
      of the ridge also significantly contributed to the enhanced performance of this
      type of graft. Building on these conclusions, an enhanced configuration of spiral
      graft is proposed and compared against conventional and spiral grafts to reaffirm
      its potential benefits.

PMID- 28500312
TI  - Total tumour diameter is superior to unifocal diameter as a predictor of
      papillary thyroid microcarcinoma prognosis.
AB  - The current American Joint Committee (AJCC) on Cancer TNM classification does not
      describe the treatment of multifocal papillary thyroid microcarcinomas (PTMCs)
      with a total tumour diameter (TTD) >1 cm. Herein, we investigated this PTMC
      subgroup in terms of extrathyroidal extension (ETE), local infiltration, central
      lymph node metastasis (LNM), and prognosis. Consecutive patients (n = 1102) were
      identified and the proportions of LNM, ETE, and local infiltration were similar
      between PTCs with a unifocal tumour diameter >1 cm and <=2 cm and PTMCs with a
      multifocal TTD >1 cm and <=2 cm. The proportions of LNM, ETE, and local
      infiltration were also similar between PTMCs with a unifocal diameter <=1 cm vs.
      multifocal TTD <=1 cm. However, when comparing PTMCs with a unifocal diameter <=1
      cm vs. multifocal TTD >1 cm, significant differences were observed. In the Kaplan
      Meier analysis, significant differences were observed between PTMCs with a
      unifocal diameter <=1 cm vs. multifocal TTD >1 cm and multifocal TTD <=1 cm vs.
      multifocal TTD >1 cm. Accordingly, TTD may represent a more accurate criterion
      for tumour size of PTCs and should be considered in the revised AJCC staging
      system.

PMID- 28500313
TI  - The mitochondrial genomes of the acoelomorph worms Paratomella rubra, Isodiametra
      pulchra and Archaphanostoma ylvae.
AB  - Acoels are small, ubiquitous - but understudied - marine worms with a very simple
      body plan. Their internal phylogeny is still not fully resolved, and the position
      of their proposed phylum Xenacoelomorpha remains debated. Here we describe
      mitochondrial genome sequences from the acoels Paratomella rubra and Isodiametra
      pulchra, and the complete mitochondrial genome of the acoel Archaphanostoma
      ylvae. The P. rubra and A. ylvae sequences are typical for metazoans in size and
      gene content. The larger I. pulchra  mitochondrial genome contains both ribosomal
      genes, 21 tRNAs, but only 11 protein-coding genes. We find evidence suggesting a
      duplicated sequence in the I. pulchra mitochondrial genome. The P. rubra, I.
      pulchra and A. ylvae mitochondria have a unique genome organisation in comparison
      to other metazoan mitochondrial genomes. We found a large degree of protein
      coding gene and tRNA overlap with little non-coding sequence in the compact P.
      rubra genome. Conversely, the A. ylvae and I. pulchra genomes have many long non
      coding sequences between genes, likely driving genome size expansion in the
      latter. Phylogenetic trees inferred from mitochondrial genes retrieve
      Xenacoelomorpha as an early branching taxon in the deuterostomes. Sequence
      divergence analysis between P. rubra sampled in England and Spain indicates
      cryptic diversity.

PMID- 28500314
TI  - Activation of Eosinophils Interacting with Bronchial Epithelial Cells by
      Antimicrobial Peptide LL-37: Implications in Allergic Asthma.
AB  - The role of antimicrobial peptide LL-37 in asthma exacerbation is unclear.
      Microbial infection, which is the most common inducer of asthma exacerbation, is
      accompanied by elevated LL-37. The present study found that co-culture of
      eosinophils and bronchial epithelial cell line BEAS-2B significantly enhanced
      intercellular adhesion molecule-1 on both cells and CD18 expression on
      eosinophils upon LL-37 stimulation. IL-6, CXCL8 and CCL4 were substantially
      released in co-culture in the presence of LL-37. LL-37 triggered the activation
      of eosinophils interacting with BEAS-2B cells in a P2X purinoceptor 7/epidermal
      growth factor receptor-dependent manner. Eosinophils and BEAS-2B cells
      differentially contribute to the expression of cytokines/chemokines in co
      culture, while soluble mediators were sufficient to mediate the intercellular
      interactions. Intracellular p38-mitogen-activated protein kinase, extracellular
      signal-regulated kinase and NF-kappaB signaling pathways were essential for LL-37
      mediated activation of eosinophils and BEAS-2B cells. By using the ovalbumin
      induced asthmatic model, intranasal administration of mCRAMP (mouse ortholog of
      LL-37) in combination with ovalbumin during the allergen challenge stage
      significantly enhanced airway hyperresponsiveness and airway inflammation in
      sensitized mice, thereby implicating a deteriorating role of LL-37 in allergic
      asthma. This study provides evidence of LL-37 in triggering asthma exacerbation
      via the activation of eosinophils interacting with bronchial epithelial cells in
      inflammatory airway.

PMID- 28500315
TI  - Network and role analysis of autophagy in Phytophthora sojae.
AB  - Autophagy is an evolutionarily conserved mechanism in eukaryotes with roles in
      development and the virulence of plant fungal pathogens. However, few reports on
      autophagy in oomycete species have been published. Here, we identified 26
      autophagy-related genes (ATGs) belonging to 20 different groups in Phytophthora
      sojae using a genome-wide survey, and core ATGs in oomycetes were used to
      construct a preliminary autophagy pathway model. Expression profile analysis
      revealed that these ATGs are broadly expressed and that the majority of them
      significantly increase during infection stages, suggesting a central role for
      autophagy in virulence. Autophagy in P. sojae was detected using a GFP-PsAtg8
      fusion protein and the fluorescent dye MDC during rapamycin and starvation
      treatment. In addition, autophagy was significantly induced during sporangium
      formation and cyst germination. Silencing PsAtg6a in P. sojae significantly
      reduced sporulation and pathogenicity. Furthermore, a PsAtg6a-silenced strain
      showed haustorial formation defects. These results suggested that autophagy might
      play essential roles in both the development and infection mechanism of P. sojae.

PMID- 28500316
TI  - Establishment of a Strong Link Between Smoking and Cancer Pathogenesis through
      DNA Methylation Analysis.
AB  - Smoking is a well-documented risk factor in various cancers, especially lung
      cancer. In the current study, we tested the hypothesis that abnormal DNAm loci
      associated with smoking are enriched in genes and pathways that convey a risk of
      cancer by determining whether smoking-related methylated genes led to enrichment
      in cancer-related pathways. We analyzed two sets of smoking-related methylated
      genes from 28 studies originating from blood and buccal samples. By analyzing 320
      methylated genes from 26 studies on blood samples (N = 17,675), we found 57
      enriched pathways associated with different types of cancer (FDR < 0.05). Of
      these, 11 were also significantly overrepresented in the 661 methylated genes
      from two studies of buccal samples (N = 1,002). We further found the aryl
      hydrocarbon receptor signaling pathway plays an important role in the initiation
      of smoking-attributable cancer. Finally, we constructed a subnetwork of genes
      important for smoking-attributable cancer from the 48 non-redundant genes in the
      11 oncogenic pathways. Of these, genes such as DUSP4 and AKT3 are well documented
      as being involved in smoking-related lung cancer. In summary, our findings
      provide robust and systematic evidence in support of smoking's impact on the
      epigenome, which may be an important contributor to cancer.

PMID- 28500317
TI  - Optical properties of monolayer tinene in electric fields.
AB  - The absorption spectra of monolayer tinene in perpendicular electric fields are
      studied by the tight-binding model. There are three kinds of special structures,
      namely shoulders, logarithmical symmetric peaks and asymmetric peaks in the
      square-root form, corresponding to the optical excitations of the extreme points,
      saddle points and constant-energy loops. With the increasing field strength, two
      splitting shoulder structures, which are dominated by the parabolic bands of 5p z
      orbitals, come to exist because of the spin-split energy bands. The frequency of
      threshold shoulder declines to zero and then linearly grows. The third shoulder
      at 0.75~0.85 eV mainly comes from (5p x , 5p y ) orbitals. The former and the
      latter orbitals, respectively, create the saddle-point symmetric peaks near the M
      point, while they hybridize with one another to generate the loop-related
      asymmetric peaks. Tinene quite differs from graphene, silicene, and germanene.
      The special relationship among the multi-orbital chemical bondings, spin-orbital
      couplings and Coulomb potentials accounts for the feature-rich optical
      properties.

PMID- 28500318
TI  - Direct Observation of Sink-Dependent Defect Evolution in Nanocrystalline Iron
      under Irradiation.
AB  - Crystal defects generated during irradiation can result in severe changes in
      morphology and an overall degradation of mechanical properties in a given
      material. Nanomaterials have been proposed as radiation damage tolerant
      materials, due to the hypothesis that defect density decreases with grain size
      refinement due to the increase in grain boundary surface area. The lower defect
      density should arise from grain boundary-point defect absorption and enhancement
      of interstitial-vacancy annihilation. In this study, low energy helium ion
      irradiation on free-standing iron thin films were performed at 573 K.
      Interstitial loops of a 0 /2 [111] Burgers vector were directly observed as a
      result of the displacement damage. Loop density trends with grain size
      demonstrated an increase in the nanocrystalline (<100 nm) regime, but scattered
      behavior in the transition from the nanocrystalline to the ultra-fine regime (100
      500 nm). To examine the validity of such trends, loop density and area for
      different grains at various irradiation doses were compared and revealed
      efficient defect absorption in the nanocrystalline grain size regime, but loop
      coalescence in the ultra-fine grain size regime. A relationship between the
      denuded zone formation, a measure of grain boundary absorption efficiency, grain
      size, grain boundary type and misorientation angle is determined.

PMID- 28500320
TI  - Oral administration of trace element magnesium significantly improving the
      cognition and locomotion in hepatic encephalopathy rats.
AB  - The therapeutic effects of iron, zinc and magnesium trace elements, as well as
      rifaximin were investigated and compared in HE rats. In this study, HE rats were
      treated with either ferrous sulfate (HE-Fe, 30 mg/kg/day), zinc sulfate (HE-Zn,
      30 mg/kg/day), magnesium sulfate (HE-Mg, 50 mg/kg/day) or rifaximin (HE-Rf, 50
      mg/kg/day), which was mixed with water and administered orally for 61 days. The
      Morris water maze (MWM) and open-field tests were used to evaluate cognitive and
      locomotor function. The blood ammonia levels before and after administration of
      the glutamine challenge test, manganese concentration and glutamine synthetase
      (GS) activity were measured. Significantly longer MWM escape latencies, less
      locomotor activity, higher blood ammonia levels, higher brain manganese
      concentrations and higher GS activity were observed in HE rats. However, HE-Mg
      and HE-Rf rats had significantly shorter MWM escape latencies, increased
      locomotor activity, lower blood ammonia, lower brain manganese concentrations and
      lower GS activity. Partial improvements were observed in HE-Fe and HE-Zn rats.
      The results indicated that oral administration of magnesium can significantly
      improve the cognitive and locomotor functions in HE rats by reducing the brain
      manganese concentration and regulating GS activity.

PMID- 28500319
TI  - Airway Microbial Diversity is Inversely Associated with Mite-Sensitized Rhinitis
      and Asthma in Early Childhood.
AB  - Microbiota plays an important role in regulating immune responses associated with
      atopic diseases. We sought to evaluate relationships among airway microbiota,
      serum IgE levels, allergic sensitization and their relevance to rhinitis and
      asthma. Microbial characterization was performed using Illumina-based 16S rRNA
      gene sequencing of 87 throat swabs collected from children with asthma (n = 32)
      and rhinitis (n = 23), and from healthy controls (n = 32). Data analysis was
      performed using QIIME (Quantitative Insights Into Microbial Ecology) v1.8.
      Significantly higher abundance of Proteobacteria was found in children with
      rhinitis than in the healthy controls (20.1% vs. 16.1%, P = 0.009). Bacterial
      species richness (Chao1 index) and diversity (Shannon index) were significantly
      reduced in children with mite sensitization but not in those with food or IgE
      sensitization. Compared with healthy children without mite sensitization, the
      mite-sensitized children with rhinitis and asthma showed significantly lower
      Chao1 and Shannon indices. Moraxella and Leptotrichia species were significantly
      found in the interaction of mite sensitization with rhinitis and asthma
      respectively. Airway microbial diversity appears to be inversely associated with
      sensitization to house dust mites. A modulation between airway dysbiosis and
      responses to allergens may potentially cause susceptibility to rhinitis and
      asthma in early childhood.

PMID- 28500321
TI  - Twinning-induced plasticity (TWIP) and work hardening in Ti-based metallic glass
      matrix composites.
AB  - The present study demonstrates that Ti-based metallic glass matrix composites
      (MGMCs) with a normal composition of Ti43Zr32Ni6Ta5Be14 containing ductile
      dendrites dispersed in the glass matrix has been developed, and deformation
      mechanisms about the tensile property have been investigated by focusing on
      twinning-induced plasticity (TWIP) effect. The Ti-based MGMC has excellent
      tensile properties and pronounced tensile work-hardening capacity, with a yield
      strength of 1100 MPa and homogeneous elongation of 4%. The distinguished strain
      hardening is ascribed to the formation of deformation twinning within the
      dendrites. Twinning generated in the dendrites works as an obstacle for the rapid
      propagation of shear bands, and then, the localized necking is avoided, which
      ensures the ductility of such kinds of composites. Besides, a finite-element
      model (FEM) has been established to explain the TWIP effect which brings out a
      work-hardening behavior in the present MGMC instead of a localized strain
      concentration. According to the plasticity theory of traditional crystal
      materials and some new alloys, TWIP effect is mainly controlled by stacking fault
      energy (SFE), which has been analyzed intensively in the present MGMC.

PMID- 28500322
TI  - Incidence and predictors of HBV relapse after cessation of nucleoside analogues
      in HBeAg-negative patients with HBsAg <= 200 IU/mL.
AB  - The predictors of hepatitis B virus (HBV) relapse and HBsAg loss after cessation
      of nucleos(t)ide analogues (NA) in HBeAg-negative patients with end-of-treatment
      HBsAg <= 200 IU/mL remains unclear. The study recruited 119 chronic hepatitis B
      (CHB) patients who achieved end-of-treatment HBsAg <= 200 IU/mL, were treated
      with lamivudine (n = 34) and entecavir (n = 85). The 5-year rates of post
      treatment virological relapse, clinical relapse, and HBsAg loss at 60 months were
      39.4%, 27.6%, and 45.9%, respectively. Cox regression analysis revealed that HBV
      DNA at entry and end-of-treatment HBsAg levels were independent predictors of
      virolgical and clinical relapse. HBV genotype C and end-of-treatment HBsAg were
      independent factors of HBsAg loss. Patients with a combination of end-of
      treatment HBsAg < 50 IU/mL and HBV DNA < 2 * 105 IU/mL at entry experienced the
      lowest virological and clinical relapse rates (5% and 0% at 60 months,
      respectively). In contract, patients with a combination of end-of-treatment HBsAg
      >= 50 IU/mL and HBV DNA >= 2 * 105 IU/mL at entry experienced high virological
      and clinical relapse (80.7% and 71.5% at 60 months, respectively). No patients
      experienced hepatic decompensation when clinical relapse occurred after timely
      retreatment. A combination of HBV DNA levels at entry and end-of-treatment HBsAg
      levels was useful for predicting the post-treatment HBV relapse in HBeAg-negative
      patients with HBsAg <= 200 IU/mL.

PMID- 28500323
TI  - Development of an inducible mouse model of iRFP713 to track recombinase activity
      and tumour development in vivo.
AB  - While the use of bioluminescent proteins for molecular imaging is a powerful
      technology to further our understanding of complex processes, fluorescent
      labeling with visible light fluorescent proteins such as GFP and RFP suffers from
      poor tissue penetration and high background autofluorescence. To overcome these
      limitations, we generated an inducible knock-in mouse model of iRFP713. This
      model was used to assess Cre activity in a Rosa Cre-ER background and quantify
      Cre activity upon different tamoxifen treatments in several organs. We also show
      that iRFP can be readily detected in 3D organoid cultures, FACS analysis and in
      vivo tumour models. Taken together we demonstrate that iRFP713 is a progressive
      step in in vivo imaging and analysis that widens the optical imaging window to
      the near-infrared spectrum, thereby allowing deeper tissue penetration, quicker
      image acquisition without the need to inject substrates and a better signal to
      background ratio in genetically engineered mouse models (GEMMs).

PMID- 28500324
TI  - Labeling Extracellular Vesicles for Nanoscale Flow Cytometry.
AB  - Extracellular vesicles (EVs), including exosomes and microvesicles, are 30-800 nm
      vesicles that are released by most cell types, as biological packages for
      intercellular communication. Their importance in cancer and inflammation makes
      EVs and their cargo promising biomarkers of disease and cell-free therapeutic
      agents. Emerging high-resolution cytometric methods have created a pressing need
      for efficient fluorescent labeling procedures to visualize and detect EVs.
      Suitable labels must be bright enough for one EV to be detected without the
      generation of label-associated artifacts. To identify a strategy that robustly
      labels individual EVs, we used nanoFACS, a high-resolution flow cytometric method
      that utilizes light scattering and fluorescence parameters along with sample
      enumeration, to evaluate various labels. Specifically, we compared lipid-,
      protein-, and RNA-based staining methods and developed a robust EV staining
      strategy, with the amine-reactive fluorescent label, 5-(and-6)-Carboxyfluorescein
      Diacetate Succinimidyl Ester, and size exclusion chromatography to remove
      unconjugated label. By combining nanoFACS measurements of light scattering and
      fluorescence, we evaluated the sensitivity and specificity of EV labeling assays
      in a manner that has not been described for other EV detection methods. Efficient
      characterization of EVs by nanoFACS paves the way towards further study of EVs
      and their roles in health and disease.

PMID- 28500325
TI  - Catechol-Functional Chitosan/Silver Nanoparticle Composite as a Highly Effective
      Antibacterial Agent with Species-Specific Mechanisms.
AB  - In this study, silver nanoparticles (Ag NPs) coated with catechol-conjugated
      chitosan (CSS) were prepared using green methods. Interestingly, we uncovered
      that CSS-coated Ag NPs (CSS-Ag NPs) exhibited a higher toxicity against gram
      negative Escherichia coli (E. coli) bacteria than against gram-positive
      Staphylococcus aureus (S. aureus) bacteria. The differences revealed that the CSS
      Ag NPs killed gram bacteria with distinct, species-specific mechanisms. The aim
      of this study is to further investigate these underlying mechanisms through a
      series of analyses. The ultrastructure and morphology of the bacteria before and
      after treatment with CSS-Ag NPs were observed. The results demonstrated the CSS
      Ag NPs killed gram-positive bacteria through a disorganization of the cell wall
      and leakage of cytoplasmic content. In contrast, the primary mechanism of action
      on gram-negative bacteria was a change in membrane permeability, induced by
      adsorption of CSS-Ag NPs. The species-specific mechanisms are caused by
      structural differences in the cell walls of gram bacteria. Gram-positive bacteria
      are protected from CSS-Ag NPs by a thicker cell wall, while gram-negatives are
      more easily killed due to an interaction between a special outer membrane and the
      nanoparticles. Our study offers an in-depth understanding of the antibacterial
      behaviors of CSS-Ag NPs and provides insights into ultimately optimizing the
      design of Ag NPs for treatment of bacterial infections.

PMID- 28500327
TI  - Metazoan Ribosome Inactivating Protein encoding genes acquired by Horizontal Gene
      Transfer.
AB  - Ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a
      specific adenine residue in the conserved sarcin/ricin loop of 28S rRNA. These
      enzymes are widely distributed among plants and their presence has also been
      confirmed in several bacterial species. Recently, we reported for the first time
      in silico evidence of RIP encoding genes in metazoans, in two closely related
      species of insects: Aedes aegypti and Culex quinquefasciatus. Here, we have
      experimentally confirmed the presence of these genes in mosquitoes and attempted
      to unveil their evolutionary history. A detailed study was conducted, including
      evaluation of taxonomic distribution, phylogenetic inferences and microsynteny
      analyses, indicating that mosquito RIP genes derived from a single Horizontal
      Gene Transfer (HGT) event, probably from a cyanobacterial donor species.
      Moreover, evolutionary analyses show that, after the HGT event, these genes
      evolved under purifying selection, strongly suggesting they play functional roles
      in these organisms.

PMID- 28500326
TI  - Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated
      with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation.
AB  - We previously reported that activation of the host autophagic protein, Beclin1,
      by HIV-1 infection represents an essential mechanism in controlling HIV
      replication and viral-induced inflammatory responses in microglial cells.
      Existing antiretroviral therapeutic approaches have been limited in their ability
      to cross the blood-brain barrier effectively and recognize and selectively
      eliminate persistent HIV-infected brain reservoirs. In the present study and for
      the first time, the bio-distribution and efficacy of noninvasive intranasal
      delivery of small interfering RNA (siRNA) against the Beclin1 gene using the
      cationic linear polyethylenimines (PEI) as a gene carrier was investigated in
      adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA
      delivered intranasally was found in the cytoplasm of neurons and glial cells of
      the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse
      immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1
      significantly depleted the target protein expression levels in brain tissues with
      no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and
      confirmed by Raman spectroscopy. These results indicate that the intranasal drug
      delivery allows for the direct delivery of the PEI-siRNA nano-complex to the
      central nervous system, which could potentially offer an efficient means of gene
      silencing-mediated therapy in the HIV-infected brain.

PMID- 28500328
TI  - Spatial topologies affect local food web structure and diversity in evolutionary
      metacommunities.
AB  - An important challenge in theoretical ecology is to better predict ecological
      responses to environmental change, and in particular to spatial changes such as
      habitat fragmentation. Classical food-web models have focused on purely
      ecological predictions, without taking adaptation or evolution of species traits
      into account. We address this issue using an eco-evolutionary model, which is
      based on body masses and diets as the key traits that determine metabolic rates
      and trophic interactions. The model implements evolution by the introduction of
      new morphs that are related to the existing ones, so that the network structure
      itself evolves in a self-organized manner. We consider the coupling and
      decoupling of habitats in multi-trophic metacommunities consisting of 2 or 4
      habitats. Our model thus integrates metacommunity models, which describe
      ecosystems as networks of networks, with large community evolution models. We
      find that rescue effects and source-sink effects occur within coupled habitats,
      which have the potential to change local selection pressures so that the local
      food web structure shows a fingerprint of its spatial conditions. Within our
      model system, we observe that habitat coupling increases the lifetimes of top
      predators and promotes local biodiversity.

PMID- 28500329
TI  - No evidence of inbreeding depression in a Tasmanian devil insurance population
      despite significant variation in inbreeding.
AB  - Inbreeding depression occurs when inbred individuals experience reduced fitness
      as a result of reduced genome-wide heterozygosity. The Tasmanian devil faces
      extinction due to a contagious cancer, devil facial tumour disease (DFTD). An
      insurance metapopulation was established in 2006 to ensure the survival of the
      species and to be used as a source population for re-wilding and genetic rescue.
      The emergence of DFTD and the rapid decline of wild devil populations have
      rendered the species at risk of inbreeding depression. We used 33 microsatellite
      loci to (1) reconstruct a pedigree for the insurance population and (2) estimate
      genome-wide heterozygosity for 200 individuals. Using heterozygosity-fitness
      correlations, we investigated the effect of heterozygosity on six diverse fitness
      measures (ulna length, asymmetry, weight-at-weaning, testes volume, reproductive
      success and survival). Despite statistically significant evidence of variation in
      individual inbreeding in this population, we found no associations between
      inbreeding and any of our six fitness measurements. We propose that the benign
      environment in captivity may decrease the intensity of inbreeding depression,
      relative to the stressful conditions in the wild. Future work will need to
      measure fitness of released animals to facilitate translation of this data to the
      broader conservation management of the species in its native range.

PMID- 28500330
TI  - Genotyping-by-sequencing of three mapping populations for identification of
      candidate genomic regions for resistance to sterility mosaic disease in
      pigeonpea.
AB  - Sterility mosaic disease (SMD) is one of the serious production constraints that
      may lead to complete yield loss in pigeonpea. Three mapping populations including
      two recombinant inbred lines and one F2, were used for phenotyping for SMD
      resistance at two locations in three different years. Genotyping-by-sequencing
      approach was used for simultaneous identification and genotyping of SNPs on above
      mentioned populations. In total, 212,464, 89,699 and 64,798 SNPs were identified
      in ICPL 20096 * ICPL 332 (PRIL_B), ICPL 20097 * ICP 8863 (PRIL_C) and ICP 8863 *
      ICPL 87119 (F2) respectively. By using high-quality SNPs, genetic maps were
      developed for PRIL_B (1,101 SNPs; 921.21 cM), PRIL_C (484 SNPs; 798.25 cM) and F2
      (996 SNPs; 1,597.30 cM) populations. The average inter marker distance on these
      maps varied from 0.84 cM to 1.65 cM, which was lowest in all genetic mapping
      studies in pigeonpea. Composite interval mapping based QTL analysis identified a
      total of 10 QTLs including three major QTLs across the three populations. The
      phenotypic variance of the identified QTLs ranged from 3.6 to 34.3%. One
      candidate genomic region identified on CcLG11 seems to be promising QTL for
      molecular breeding in developing superior lines with enhanced resistance to SMD.

PMID- 28500331
TI  - Transcriptome sequencing and phylogenetic analysis of four species of luminescent
      beetles.
AB  - The evolution of bioluminescence has prompted scientific attention to illuminate
      phylogenetic relationships of luminescent beetles. However, genomic resources are
      virtually lacking in rhagophthalmids (Rhagophthalmidae) and their related firefly
      beetles lampyrids (Lampyridae). Here, we employed the Illumina Hiseq 2000
      platform and sequenced the whole-body transcriptomes of the four luminescent
      beetles: one rhagophthalmid (Rhagophthalmus sp.) and three fireflies
      (Asymmetricata circumdata, Aquatica ficta, and Pyrocoelia pectoralis). We
      obtained 55.4, 43.4, 38.6, and 36.7 million clean reads for the four species,
      respectively. All reads were assembled into contigs from which unigenes were
      derived. All unigenes were annotated by publicly available databases, and a total
      of 4325 orthologous genes were identified. Using multiple phylogenetic
      approaches, our transcriptome data confirmed the distinctiveness of
      Rhagophthalmidae from Lampyridae, which was also supported by our mitogenome
      analysis using three newly determined mitogenome sequences and 12 previously
      published ones. Together, this study is the first report of whole transcriptome
      sequencing data in Rhagophthalmidae and Lampyridae species, representing a
      valuable genomic resource for studying the origin and evolution of some
      remarkable traits in these beetles such as bioluminescence. Moreover, our
      transcriptome and mitogenome data provide useful phylogenetic information that
      could be of importance in future studies of phylogenetic inference.

PMID- 28500333
TI  - Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing.
AB  - Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which
      is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal
      aneuploidies using massively parallel sequencing. Because of the low percentage
      of fetal DNA, methods with high sensitivity and precision are required. However,
      sequencing variation lowers sensitivity and hampers detection of trisomy samples.
      Therefore, we have developed three algorithms to improve sensitivity and
      specificity: the chi-squared-based variation reduction (chi2VR), the regression
      based Z-score (RBZ) and the Match QC score. The chi2VR reduces variability in
      sequence read counts per chromosome between samples, the RBZ allows for more
      precise trisomy prediction, and the Match QC score shows if the control group
      used is representative for a specific sample. We compared the performance of
      chi2VR to that of existing variation reduction algorithms (peak and GC
      correction) and that of RBZ to trisomy prediction algorithms (standard Z-score,
      normalized chromosome value and median-absolute-deviation-based Z-score). chi2VR
      and the RBZ both reduce variability more than existing methods, and thereby
      increase the sensitivity of the NIPT analysis. We found the optimal combination
      of algorithms was to use both GC correction and chi2VR for pre-processing and to
      use RBZ as the trisomy prediction method.

PMID- 28500334
TI  - Using change trajectories to study the impacts of multi-annual habitat loss on
      fledgling production in an old forest specialist bird.
AB  - The loss and subdivision of habitat into smaller and more spatially isolated
      units due to human actions has been shown to adversely affect species worldwide.
      We examined how changes in old forest cover during eight years were associated
      with the cumulative number of fledged offspring at the end of study period in
      Eurasian treecreepers (Certhia familiaris) in Central Finland. We were
      specifically interested in whether the initial level of old forest cover
      moderated this relation. We applied a flexible and powerful approach, latent
      growth curve modelling in a structural equation modeling (SEM) framework, to
      create trajectories describing changes in old forest cover through time, and
      studied how this change at both the territory core and landscape scales impacted
      fledging numbers. Our main finding was that at the territory core scale the
      negative impact of habitat loss on fledging numbers was lessened by the higher
      levels of initial forest cover, while no association was found at the landscape
      scale. Our study highlights a powerful, but currently under-utilised methodology
      among ecologists that can provide important information about biological
      responses to changes in the environment, providing a mechanistic way to study how
      land cover dynamics can affect species responses.

PMID- 28500332
TI  - Sexual homomorphism in dioecious trees: extensive tests fail to detect sexual
      dimorphism in Populus ?.
AB  - The evolution of sexual dimorphism and expansion of sex chromosomes are both
      driven through sexual conflict, arising from differing fitness optima between
      males and females. Here, we pair work in poplar (Populus) describing one of the
      smallest sex-determining regions known thus far in complex eukaryotes (~100 kbp)
      with comprehensive tests for sexual dimorphism using >1300 individuals from two
      Populus species and assessing 96 non-reproductive functional traits. Against
      expectation, we found sexual homomorphism (no non-reproductive trait differences
      between the sexes), suggesting that gender is functionally neutral with respect
      to non-reproductive features that affect plant survival and fitness. Combined
      with a small sex-determining region, we infer that sexual conflict may be
      effectively stymied or non-existent within these taxa. Both sexual homomorphism
      and the small sex-determining region occur against a background of strong
      environmental selection and local adaptation in Populus. This presents a powerful
      hypothesis for the evolution of dioecious species. Here, we suggest that
      environmental selection may be sufficient to suppress and stymy sexual conflict
      if it acts orthogonal to sexual selection, thereby placing limitations on the
      evolution of sexual dimorphism and genomic expansion of sex chromosomes.

PMID- 28500335
TI  - Nutrient consumption and chain tuning in diatoms exposed to storm-like
      turbulence.
AB  - Current information on the response of phytoplankton to turbulence is linked to
      cell size and nutrient availability. Diatoms are considered to be favored by
      mixing as dissolved nutrients are more easily accessible for non-motile cells. We
      investigated how diatoms exploit microscale turbulence under nutrient repletion
      and depletion conditions. Here, we show that the chain-forming diatom Chaetoceros
      decipiens, continues to take up phosphorus and carbon even when silicon is
      depleted during turbulence. Our findings indicate that upon silica depletion,
      during turbulence, chain spectra of C. decipiens remained unchanged. We show here
      that longer chains are maintained during turbulence upon silica depletion whereas
      under still conditions, shorter chains are enriched. We interpret this as a sign
      of good physiological state leading to a delay of culture senescence. Our results
      show that C. decipiens senses and responds to turbulence both in nutrient
      repletion and depletion. This response is noteworthy due to the small size of the
      species. The coupling between turbulence and biological response that we depict
      here may have significant ecological implications. Considering the predicted
      increase of storms in Northern latitudes this response might modify community
      structure and succession. Our results partly corroborate Margalef's mandala and
      provide additional explanations for that conceptualization.

PMID- 28500336
TI  - Phylogeographical structure and demographic expansion in the endemic alpine
      stream salamander (Hynobiidae: Batrachuperus) of the Qinling Mountains.
AB  - The Qinling Mountains of China provide an excellent study area for assessing the
      effect of Pleistocene climatic oscillations and paleogeological events on
      intraspecific diversification. To assess genetic diversity of an endemic stream
      salamander, Batrachuperus tibetanus, for its conservation, a phylogeographical
      survey was performed based on mitochondrial DNA and morphological data. The
      mitochondrial data revealed three lineages of B. tibetanus in the Qinling
      Mountains. A lineage present in the northwestern Qinling Mountains groups with
      the Tibet lineage of B. tibetanus, and the remaining Qinling populations are
      eastern and western lineages that separated ~3-4 million years ago (Ma). The
      eastern and western Qinling lineage delineation is supported by three
      morphological variables (snout length, eye diameter and axilla-groin length). The
      divergence of the two major lineages was likely caused by orogenesis of the
      Qinling Mountains during the late Cenozoic, and the two lineages were
      subsequently affected at different levels by Pleistocene climatic oscillations
      showing different signals of demographic expansion. A large suitable area of B.
      tibetanus through the Qinling Mountains since the last glacial maximum (LGM)
      indicated the adaptation of this species to the climatic changes. However, low
      genetic diversity within populations indicate the urgency of preserving the
      vulnerable populations and endemic lineages.

PMID- 28500337
TI  - Examining the efficacy of intravenous administration of predatory bacteria in
      rats.
AB  - The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are
      obligate predators of Gram-negative bacteria, and have been proposed to be used
      to treat multidrug-resistant bacterial infections. The ability of predatory
      bacteria to reduce bacterial burden in vivo within the lungs of rats has been
      demonstrated, but it was unknown if predatory bacteria can attenuate systemic
      bacterial burden administered intravenously. In this study, we first assessed the
      safety of intravenous inoculation of predatory bacteria in rats. No rat morbidity
      or adverse histopathology of various organs due to predatory bacteria
      administration was observed. An increase in proinflammatory cytokines (TNFalpha
      and KC/GRO) was observed at two hours post-inoculation; however, cytokines
      returned to baseline levels by 18 hours. Furthermore, bacterial dissemination
      analysis demonstrated that predatory bacteria were efficiently cleared from the
      host by 20 days post-injection. To determine whether predatory bacteria could
      reduce bacterial burden in vivo, Klebsiella pneumoniae was injected into the tail
      veins of rats and followed with multiple doses of predatory bacteria over 16 or
      24 hours. Predatory bacteria were unable to significantly reduce K. pneumoniae
      burden in the blood or prevent dissemination to other organs. The results suggest
      that predatory bacteria may not be effective for treatment of acute blood
      infections.

PMID- 28500338
TI  - Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas
      aeruginosa identified in association with oral squamous cell carcinoma.
AB  - Studies on the possible association between bacteria and oral squamous cell
      carcinoma (OSCC) remain inconclusive, largely due to methodological
      variations/limitations. The objective of this study was to characterize the
      species composition as well as functional potential of the bacteriome associated
      with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep
      epithelium swabs (matched control subjects) was sequenced for the V1-V3 region
      using Illumina's 2 * 300 bp chemistry. High quality, non-chimeric merged reads
      were classified to species level using a prioritized BLASTN-algorithm. Downstream
      analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum
      subsp. polymorphum was the most significantly overrepresented species in the
      tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44,
      while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae
      were the most significantly abundant in the controls. Functional prediction
      showed that genes involved in bacterial mobility, flagellar assembly, bacterial
      chemotaxis and LPS synthesis were enriched in the tumors while those responsible
      for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and
      tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were
      significantly associated with the controls. This is the first epidemiological
      evidence for association of F. nucleatum and P. aeruginosa with OSCC.
      Functionally, an "inflammatory bacteriome" is enriched in OSSC.

PMID- 28500339
TI  - A role for core planar polarity proteins in cell contact-mediated orientation of
      planar cell division across the mammalian embryonic skin.
AB  - The question of how cell division orientation is determined is fundamentally
      important for understanding tissue and organ shape in both healthy or disease
      conditions. Here we provide evidence for cell contact-dependent orientation of
      planar cell division in the mammalian embryonic skin. We propose a model where
      the core planar polarity proteins Celsr1 and Frizzled-6 (Fz6) communicate the
      long axis orientation of interphase basal cells to neighbouring basal mitoses so
      that they align their horizontal division plane along the same axis. The
      underlying mechanism requires a direct, cell surface, planar polarised cue, which
      we posit depends upon variant post-translational forms of Celsr1 protein coupled
      to Fz6. Our hypothesis has parallels with contact-mediated division orientation
      in early C. elegans embryos suggesting functional conservation between the
      adhesion-GPCRs Celsr1 and Latrophilin-1. We propose that linking planar cell
      division plane with interphase neighbour long axis geometry reinforces axial bias
      in skin spreading around the mouse embryo body.

PMID- 28500340
TI  - Both haemagglutinin-specific antibody and T cell responses induced by a
      chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral
      challenge.
AB  - Since 2013, the outbreak or sporadic infection of a new reassortant H7N9
      influenza virus in China has resulted in hundreds of deaths and thousands of
      illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine
      against H7N9 influenza is currently not available. Here, we developed a
      recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9
      haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The
      efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For
      comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice
      and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA
      vaccine prime-adenovirus boost regimen induced potent immune responses in animals
      and completely protected mice from lethal H7N9 influenza viral challenge. A post
      immunization serum transfer experiment showed that antibody responses could
      completely protect against lethal challenge, while a T cell depletion experiment
      indicated that HA-specific CD8+ T cells responses also contributed to protection.
      Therefore, both HA-specific humoral immunity and cellular immunity play important
      roles in the protection. These data suggest that the chimpanzee adenovirus
      expressing HA is a promising vaccine candidate for H7N9 virus or other influenza
      viral subtypes.

PMID- 28500342
TI  - Controllability of complex networks with unilateral inputs.
AB  - In this paper, we study the problem of controlling complex networks with
      unilateral controls, i.e., controls which can assume only positive or negative
      values, not both. Given a complex network represented by the adjacency matrix A,
      an algorithm is developed that constructs an input matrix B such that the
      resulting system (A, B) is controllable with a near minimal number of unilateral
      control inputs. This is made possible by a reformulation of classical conditions
      for controllability that casts the minimal unilateral input selection problem
      into well known optimization problems. We identify network properties that make
      unilateral controllability relatively easy to achieve as compared to unrestricted
      controllability. The analysis of the network topology for instance allows us to
      establish theoretical bounds on the minimal number of controls required. For
      various categories of random networks as well as for a number of real-world
      networks these lower bounds are often achieved by our heuristics.

PMID- 28500344
TI  - Quantitative trait loci for large sink capacity enhance rice grain yield under
      free-air CO2 enrichment conditions.
AB  - The global atmospheric CO2 concentration has been increasing annually. To
      determine the trait that effectively increases rice (Oryza sativa L.) grain yield
      under increased atmospheric CO2 concentrations, as predicted in the near future,
      we grew a chromosome segment substitution line (CSSL) and a near-isogenic line
      (NIL) producing high spikelet numbers per panicle (CSSL-GN1 and NIL-APO1,
      respectively) under free-air CO2 enrichment (FACE) conditions and examined the
      effects of a large sink capacity on grain yield, its components, and growth
      related traits under increased atmospheric CO2 concentrations. Under ambient
      conditions, CSSL-GN1 and NIL-APO1 exhibited a similar grain yield to Koshihikari,
      as a result of the trade-off between increased spikelet number and reduced grain
      filling. However, under FACE conditions, CSSL-GN1 and NIL-APO1 had an equal or a
      higher grain yield than Koshihikari because of the higher number of spikelets and
      lower reduction in grain filling. Thus, the improvement of source activity by
      increased atmospheric CO2 concentrations can lead to enhanced grain yield in rice
      lines that have a large sink capacity. Therefore, introducing alleles that
      increase sink capacity into conventional varieties represents a strategy that can
      be used to develop high-yielding varieties under increased atmospheric CO2
      concentrations, such as those predicted in the near future.

PMID- 28500341
TI  - Determinants of neuroglobin plasticity highlighted by joint coarse-grained
      simulations and high pressure crystallography.
AB  - Investigating the effect of pressure sheds light on the dynamics and plasticity
      of proteins, intrinsically correlated to functional efficiency. Here we detail
      the structural response to pressure of neuroglobin (Ngb), a hexacoordinate globin
      likely to be involved in neuroprotection. In murine Ngb, reversible coordination
      is achieved by repositioning the heme more deeply into a large internal cavity,
      the "heme sliding mechanism". Combining high pressure crystallography and coarse
      grain simulations on wild type Ngb as well as two mutants, one (V101F) with
      unaffected and another (F106W) with decreased affinity for CO, we show that Ngb
      hinges around a rigid mechanical nucleus of five hydrophobic residues (V68, I72,
      V109, L113, Y137) during its conformational transition induced by gaseous ligand,
      that the intrinsic flexibility of the F-G loop appears essential to drive the
      heme sliding mechanism, and that residue Val 101 may act as a sensor of the
      interaction disruption between the heme and the distal histidine.

PMID- 28500343
TI  - A genome scan for milk production traits in dairy goats reveals two new mutations
      in Dgat1 reducing milk fat content.
AB  - The quantity of milk and milk fat and proteins are particularly important traits
      in dairy livestock. However, little is known about the regions of the genome that
      influence these traits in goats. We conducted a genome wide association study in
      French goats and identified 109 regions associated with dairy traits. For a major
      region on chromosome 14 closely associated with fat content, the Diacylglycerol O
      Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional
      candidate gene. The caprine reference sequence of this gene was completed and 29
      polymorphisms were found in the gene sequence, including two novel exonic
      mutations: R251L and R396W, leading to substitutions in the protein sequence. The
      R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W
      mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7%
      respectively. The R396W mutation explained 46% of the genetic variance of the
      trait, and the R251L mutation 6%. Both mutations were associated with a notable
      decrease in milk fat content. Their causality was then demonstrated by a
      functional test. These results provide new knowledge on the genetic basis of milk
      synthesis and will help improve the management of the French dairy goat breeding
      program.

PMID- 28500346
TI  - Structural studies of the periplasmic portion of the diguanylate cyclase CdgH
      from Vibrio cholerae.
AB  - Cyclic diguanylate monophosphate (c-di-GMP) is a second messenger involved in
      bacterial signal transduction and produced by diguanylate cyclases (DGCs)
      generally containing highly variable periplasmic signal-recognition domains. CdgH
      is a DGC enzyme that regulates rugosity associated phenotypes in Vibrio cholerae.
      CdgH has two N-terminal tandem periplasmic substrate-binding (PBPb) domains for
      its signal recognition; however, the role of the tandem PBPb domains remains
      unclear. Here, we reported the crystal structure of the periplasmic portion of
      CdgH, which indicated that both tandem PBPb domains consist of typical interlobe
      ligand-binding architecture. Unexpectedly, the PBPb-I domain binds an L-arginine
      which apparently has been co-purified from the E. coli expression system, whereas
      the PBPb-II domain is in an unliganded open state. Structural comparison with
      other amino acid-binding proteins indicated that despite similar ligand-binding
      pockets, the PBPb-I domain possesses two ligand-binding residues (E122 and Y148)
      not conserved in homologs and involved in hydrophilic and hydrophobic
      interactions with L-arginine. Isothermal titration calorimetry indicated that the
      PBPb-I is primarily an L-arginine/L-lysine/L-ornithine-binding domain, whereas
      the PBPb-II domain exhibits a preference for L-glutamine and L-histidine.
      Remarkably, we found that the periplasmic portion of CdgH forms a stable dimer in
      solution and L-arginine binding would cause conformational changes of the dimer.

PMID- 28500345
TI  - Heterologous expression and characterization of functional mushroom tyrosinase
      (AbPPO4).
AB  - Tyrosinases are an ubiquitous group of copper containing metalloenzymes that
      hydroxylate and oxidize phenolic molecules. In an application context the term
      'tyrosinase' usually refers to 'mushroom tyrosinase' consisting of a mixture of
      isoenzymes and containing a number of enzymatic side-activities. We describe a
      protocol for the efficient heterologous production of tyrosinase 4 from Agaricus
      bisporus in Escherichia coli. Applying this procedure a pure preparation of a
      single isoform of latent tyrosinase can be achieved at a yield of 140 mg per
      liter of autoinducing culture medium. This recombinant protein possesses the same
      fold as the enzyme purified from the natural source as evidenced by single
      crystal X-ray diffraction. The latent enzyme can be activated by limited
      proteolysis with proteinase K which cleaves the polypeptide chain after K382,
      only one The latent enzyme can amino acid before the main in-vivo activation
      site. Latent tyrosinase can be used as obtained and enzymatic activity may be
      induced in the reaction mixture by the addition of an ionic detergent (e.g. 2 mM
      SDS). The proteolytically activated mushroom tyrosinase shows >50% of its maximal
      activity in the range of pH 5 to 10 and accepts a wide range of substrates
      including mono- and diphenols, flavonols and chalcones.

PMID- 28500347
TI  - Novel Fabrication and Enhanced Photocatalytic MB Degradation of Hierarchical
      Porous Monoliths of MoO3 Nanoplates.
AB  - Porous monoliths of MoO3 nanoplates were synthesized from ammonium molybdate
      (AHM) by freeze-casting and subsequent thermal treatment from 300 to 600  degrees
      C. Pure orthorhombic MoO3 phase was obtained at thermal treatment temperature of
      400  degrees C and above. MoO3 monoliths thermally treated at 400  degrees C
      displayed bimodal pore structure, including large pore channels replicating the
      ice crystals and small pores from MoO3 sheets stacking. Transmission electron
      microscopy (TEM) images revealed that the average thicknesses of MoO3 sheet were
      50 and 300 nm in porous monoliths thermally treated at 400  degrees C. The
      photocatalytic performance of MoO3 was evaluated through degradation of methylene
      blue (MB) under visible light radiation and MoO3 synthesized at 400  degrees C
      exhibited strong adsorption performance and best photocatalytic activity for
      photodegradation of MB of 99.7% under visible illumination for 60 min. MoO3
      photocatalyst displayed promising cyclic performance, and the decolorization
      efficiency of MB solution was 98.1% after four cycles.

PMID- 28500348
TI  - Penicillinase-resistant antibiotics induce non-immune-mediated cholestasis
      through HSP27 activation associated with PKC/P38 and PI3K/AKT signaling pathways.
AB  - The penicillinase-resistant antibiotics (PRAs), especially the highly prescribed
      flucloxacillin, caused frequent liver injury via mechanisms that remain largely
      non-elucidated. We first showed that flucloxacillin, independently of
      cytotoxicity, could exhibit cholestatic effects in human hepatocytes in the
      absence of an immune reaction, that were typified by dilatation of bile
      canaliculi associated with impairment of the Rho-kinase signaling pathway and
      reduced bile acid efflux. Then, we analyzed the sequential molecular events
      involved in flucloxacillin-induced cholestasis. A crucial role of HSP27 by
      inhibiting Rho-kinase activity was demonstrated using siRNA and the specific
      inhibitor KRIBB3. HSP27 activation was dependent on the PKC/P38 pathway, and led
      downstream to activation of the PI3K/AKT pathway. Other PRAs induced similar
      cholestatic effects while non PRAs were ineffective. Our results demonstrate that
      PRAs can induce cholestatic features in human hepatocytes through HSP27
      activation associated with PKC/P38 and PI3K/AKT signaling pathways and
      consequently support the conclusion that in clinic they can cause a non-immune
      mediated cholestasis that is not restricted to patients possessing certain
      genetic determinants.

PMID- 28500349
TI  - Quantitative Succinyl-Proteome Profiling of Camellia sinensis cv. 'Anji Baicha'
      During Periodic Albinism.
AB  - Lysine succinylation is a novel dynamic and evolutionarily conserved post
      translational modification (PTM) that regulates various biological processes.
      'Anji Baicha' is an albino tea variety that exhibits temperature-based
      variability of leaf colour and amino acid concentrations. However, the mechanism
      underlying albinism in 'Anji Baicha' has not been investigated at the level of
      succinylation. Here, we identify 3530 lysine succinylation sites mapped to 2132
      proteins in 'Anji Baicha', representing the first extensive data on the lysine
      succinylome in the tea plant. Eleven conserved succinylation motifs were enriched
      among the identified succinylated peptides. The protein-protein interaction maps
      were visualized using Cytoscape software. Comparison across three typical
      developmental stages of 'Anji Baicha' revealed that proteins exhibiting
      differential succinylation levels were primarily involved in photosynthesis,
      carbon fixation, biosynthesis of amino acids and porphyrin and chlorophyll
      metabolism, suggesting that these succinylated proteins are involved in 'Anji
      Baicha' leaf colour variability. These results not only deepen our understanding
      of the mechanism underlying 'Anji Baicha' albinism and the regulatory role of
      succinylation in the tea plant but also provide new insight into molecular
      breeding for leaf colour variety.

PMID- 28500352
TI  - Whole-mantle convection with tectonic plates preserves long-term global patterns
      of upper mantle geochemistry.
AB  - The evolution of the planetary interior during plate tectonics is controlled by
      slow convection within the mantle. Global-scale geochemical differences across
      the upper mantle are known, but how they are preserved during convection has not
      been adequately explained. We demonstrate that the geographic patterns of
      chemical variations around the Earth's mantle endure as a direct result of whole
      mantle convection within largely isolated cells defined by subducting plates. New
      3D spherical numerical models embedded with the latest geological paleo-tectonic
      reconstructions and ground-truthed with new Hf-Nd isotope data, suggest that
      uppermost mantle at one location (e.g. under Indian Ocean) circulates down to the
      core-mantle boundary (CMB), but returns within >=100 Myrs via large-scale
      convection to its approximate starting location. Modelled tracers pool at the CMB
      but do not disperse ubiquitously around it. Similarly, mantle beneath the Pacific
      does not spread to surrounding regions of the planet. The models fit global
      patterns of isotope data and may explain features such as the DUPAL anomaly and
      long-standing differences between Indian and Pacific Ocean crust. Indeed, the
      geochemical data suggests this mode of convection could have influenced the
      evolution of mantle composition since 550 Ma and potentially since the onset of
      plate tectonics.

PMID- 28500350
TI  - Formants provide honest acoustic cues to body size in American alligators.
AB  - In many vertebrates, acoustic cues to body size are encoded in resonance
      frequencies of the vocal tract ("formants"), rather than in the rate of tissue
      vibration in the sound source ("pitch"). Anatomical constraints on the vocal
      tract's size render formants honest cues to size in many bird and mammal species,
      but it is not clear whether this correlation evolved convergently in these two
      clades, or whether it is widespread among amniotes (mammals, birds, and non-avian
      reptiles). We investigated the potential for honest acoustic cues in the bellows
      of adult American alligators and found that formant spacing provided highly
      reliable cues to body size, while presumed correlates of the source signal did
      not. These findings held true for both sexes and for all bellows whether produced
      in or out of water. Because birds and crocodilians are the last extant
      Archosaurians and share common ancestry with all extinct dinosaurs, our findings
      support the hypothesis that dinosaurs used formants as cues to body size. The
      description of formants as honest signals in a non-avian reptile combined with
      previous evidence from birds and mammals strongly suggests that the principle of
      honest signalling via vocal tract resonances may be a broadly shared trait among
      amniotes.

PMID- 28500351
TI  - Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk
      than Targeted Effects Models.
AB  - Cancer risk is an important concern for galactic cosmic ray (GCR) exposures,
      which consist of a wide-energy range of protons, heavy ions and secondary
      radiation produced in shielding and tissues. Relative biological effectiveness
      (RBE) factors for surrogate cancer endpoints in cell culture models and tumor
      induction in mice vary considerable, including significant variations for
      different tissues and mouse strains. Many studies suggest non-targeted effects
      (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading
      to deviation from the linear dose response model used in radiation protection.
      Using the mouse Harderian gland tumor experiment, the only extensive data-set for
      dose response modelling with a variety of particle types (>4), for the first-time
      a particle track structure model of tumor prevalence is used to investigate the
      effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to
      a predicted risk 2-fold higher compared to a targeted effects model. The scarcity
      of data with animal models for tissues that dominate human radiation cancer risk,
      including lung, colon, breast, liver, and stomach, suggest that studies of NTEs
      in other tissues are urgently needed prior to long-term space missions outside
      the protection of the Earth's geomagnetic sphere.

PMID- 28500354
TI  - Assessment of Mine Water Quality Using Heavy Metal Pollution Index in a Coal
      Mining Area of Damodar River Basin, India.
AB  - A total no. of 16 mine water (underground and opencast coal mine pump discharges)
      samples were collected from East Bokaro coalfield during pre-monsoon, monsoon and
      post-monsoon seasons. The concentrations of Fe, Mn, Cu, Pb, Zn, Ni, As, Se, Al,
      Cd and Cr were determined using inductively coupled plasma mass spectrometry for
      the assessment of spatio-temporal variations, source apportionment and heavy
      metal pollution indexing. The results demonstrated that concentrations of the
      metals showed significant seasonality and most variables exhibited higher levels
      in the pre-monsoon season. The principle component analysis for ionic source
      identification was synthesized into three factors with eigen values cut off at
      greater than unity and explained about 64.8% of the total variance. The extracted
      factors seemed to be associated to the geogenic, extensive mining and allied
      transportation sources of the elements. The heavy metal pollution index (HPI) of
      the mine water calculated for the individual locations varied from 7.1 to 49.5.
      Most of the locations fall under low to medium classes of HPI except few
      locations which are under the influence of surface mining and associated
      transportation.

PMID- 28500353
TI  - Estimation of postmortem interval by vitreous potassium evaluation with a novel
      fluorescence aptasensor.
AB  - Estimation of postmortem interval (PMI) is a central role in medico-legal
      identification. Analysis of vitreous potassium ions (K+) concentration is
      frequently used by forensic workers to estimate PMI. This paper describes
      interdisciplinary research to introduce fluorescence sensing techniques into
      forensic medicine. On the basis of silver nanoclusters (AgNCs) probe stabilized
      by DNA, a simple and highly sensitive fluorescence aptasensor has been proposed
      to selectively detect K+ ions. The linear range for K+ ions was found to be 0.1
      nM-1 mM, with limit of detection of 0.06 nM. Moreover, 63 vitreous humour cases
      within 36 h after death were further studied to verify the utility of K+ ions in
      estimating the PMI. By the fluorescence aptasensor method, a new formula was
      built to determine the postmortem interval based on K+ ions concentration: PMI(h)
      = -0.55 + 1.66 * CK+(r = 0.791). And the real significance of this research was
      demonstrated by additional 6 cases with known PMIs. In comparison with the
      conventional method, the presented aptasensor strategy is cost-effective and easy
      in measuring vitreous K+, which may be potentially a better way for estimation of
      PMI in medico-legal practice.

PMID- 28500356
TI  - Intracameral cefuroxime in the prevention of postoperative endophthalmitis.

PMID- 28500355
TI  - Fabrication of Metal-Organic Framework MOF-177 Coatings on Stainless Steel Fibers
      for Head-Space Solid-Phase Microextraction of Phenols.
AB  - Direct head-space solid-phase microextraction (HS-SPME) of phenols in water is
      usually difficult due to its polarity and solubility in aqueous matrix. Herein we
      report the fabrication of metal-organic framework MOF-177 coated stainless steel
      fiber for the HS-SPME of phenols (2-methylolphenol, 4-methylolphenol, 2,4
      dimethylolphenol, 2,4-dichlorphenol, and 3-methyl-4-chlorophenol) in
      environmental water samples prior to the gas chromatography-mass spectrometry
      detection. Several parameters affecting the extraction efficiency were optimized
      in the experiment, including extraction temperature and time, the pH value and
      salt addition. The results indicated that the coated fiber gave low detection
      limits (0.015-0.043 MUg L-1) and good repeatability with the RSD ranging from
      2.8% to 5.5% for phenols. The recoveries are between 84.5%-98.6% with the spiked
      level of 10 MUg L-1 for the real water samples. The established method may afford
      a kind of potential enrichment material and a reference method for the analysis
      of methylphenols in water samples.

PMID- 28500357
TI  - Lessons from a Community-Based Program to Monitor Forest Vertebrates in the
      Brazilian Amazon.
AB  - A large number of sustainable use reserves recently have been titled in the
      Brazilian Amazonia. These reserves require public participation in the design and
      implementation of management and monitoring programs. Species-monitoring programs
      that engage local stakeholders may be useful for assessing wildlife status over
      the long term. We collaborated on the development of a participatory program to
      monitor forest vertebrates in the Piagacu-Purus Sustainable Development Reserve
      and to build capacity among the local people. We examined relations between the
      distance to the nearest human community and sighting rates of each species, and
      evaluated the program overall. Eighteen wildlife monitors received training in
      line transect and sign surveys and then conducted surveys along a total of ten
      transects. Sighting rates of most species in the Piagacu-Purus Sustainable
      Development Reserve were higher than those reported in other Amazonian forests.
      Distance to the human community was not associated with the overall vertebrate
      sighting rate. Use of the trained monitors was successful in terms of data
      acquisition and engagement. The involvement of local people promoted discussions
      about regulation of hunting in the reserve. Implementation of community-based
      programs to monitor forest wildlife in Amazonian sustainable use reserves may
      empower local communities and assess the status of wildlife through time.

PMID- 28500360
TI  - Expert's comment concerning Grand Rounds case entitled "Thoracic osteotomy for
      Gorham-Stout disease of the spine: a case report and literature review" by C.
      Maillot et al., Eur Spine J: doi 10.1007/s00586-014-3613-3.

PMID- 28500358
TI  - Injury prediction and vulnerability assessment using strain and susceptibility
      measures of the deep white matter.
AB  - Reliable prediction and diagnosis of concussion is important for its effective
      clinical management. Previous model-based studies largely employ peak responses
      from a single element in a pre-selected anatomical region of interest (ROI) and
      utilize a single training dataset for injury prediction. A more systematic and
      rigorous approach is necessary to scrutinize the entire white matter (WM) ROIs as
      well as ROI-constrained neural tracts. To this end, we evaluated injury
      prediction performances of the 50 deep WM regions using predictor variables based
      on strains obtained from simulating the 58 reconstructed American National
      Football League head impacts. To objectively evaluate performance, repeated
      random subsampling was employed to split the impacts into independent training
      and testing datasets (39 and 19 cases, respectively, with 100 trials). Univariate
      logistic regressions were conducted based on training datasets to compute the
      area under the receiver operating characteristic curve (AUC), while accuracy,
      sensitivity, and specificity were reported based on testing datasets. Two tract
      wise injury susceptibilities were identified as the best overall via pair-wise
      permutation test. They had comparable AUC, accuracy, and sensitivity, with the
      highest values occurring in superior longitudinal fasciculus (SLF; 0.867-0.879,
      84.4-85.2, and 84.1-84.6%, respectively). Using metrics based on WM fiber strain,
      the most vulnerable ROIs included genu of corpus callosum, cerebral peduncle, and
      uncinate fasciculus, while genu and main body of corpus callosum, and SLF were
      among the most vulnerable tracts. Even for one un-concussed athlete, injury
      susceptibility of the cingulum (hippocampus) right was elevated. These findings
      highlight the unique injury discriminatory potentials of computational models and
      may provide important insight into how best to incorporate WM structural
      anisotropy for investigation of brain injury.

PMID- 28500359
TI  - Effect of including damage at the tissue level in the nonlinear homogenisation of
      trabecular bone.
AB  - Being able to predict bone fracture or implant stability needs a proper
      constitutive model of trabecular bone at the macroscale in multiaxial, non
      monotonic loading modes. Its macroscopic damage behaviour has been investigated
      experimentally in the past, mostly with the restriction of uniaxial cyclic
      loading experiments for different samples, which does not allow for the
      investigation of several load cases in the same sample as damage in one direction
      may affect the behaviour in other directions. Homogenised finite element models
      of whole bones have the potential to assess complicated scenarios and thus
      improve clinical predictions. The aim of this study is to use a homogenisation
      based multiscale procedure to upscale the damage behaviour of bone from an
      assumed solid phase constitutive law and investigate its multiaxial behaviour for
      the first time. Twelve cubic specimens were each submitted to nine proportional
      strain histories by using a parallel code developed in-house. Evolution of post
      elastic properties for trabecular bone was assessed for a small range of
      macroscopic plastic strains in these nine load cases. Damage evolution was found
      to be non-isotropic, and both damage and hardening were found to depend on the
      loading mode (tensile, compression or shear); both were characterised by linear
      laws with relatively high coefficients of determination. It is expected that the
      knowledge of the macroscopic behaviour of trabecular bone gained in this study
      will help in creating more precise continuum FE models of whole bones that
      improve clinical predictions.

PMID- 28500361
TI  - [Live Animals and Staged Nature : Drawing and Photography in German Popular
      Zoology between 1860 and 1910].
AB  - It is the central thesis of this paper that the "biological perspective" (Lynn
      Nyhart) typical for Germany, with its interest in living animals, not only
      influenced natural history practices in many ways during the second half of the
      19th century, rather also shaped the illustrations of popular zoology
      publications, as for example those in Brehms Thierleben. The illustrators of this
      period preferred to use live animals as models, which they studied in zoos. These
      animals were often depicted in their "natural" habitats. Since the illustrators
      knew only very little about these habitats, they had to be imagined. Another
      fashionable genre within popular zoology was the portrayal of animals fighting,
      which attracted attention because of their drama. The first wildlife
      photographers oriented themselves on the zoological illustrations and, with the
      aid of manipulation, staging and retouching, gave their photographs the
      impression of natural surroundings and drama. Yet both the illustrators and the
      photographers emphasized their truth to nature and - based on this - the
      scientific value of their pictures. In so doing, they developed a "biological"
      kind of wildlife photography, which, after the turn of the 19th century, allowed
      dedicated amateurs to create a popular zoological oeuvre that was well received
      by broad audiences.

PMID- 28500362
TI  - MicroRNA-195 inhibits human gastric cancer by directly targeting basic fibroblast
      growth factor.
AB  - PURPOSE: Gastric cancer (GC) is one of the fatal malignancies worldwide with high
      occurrences but poor outcomes. bFGF has been shown to play significant roles in
      GC. Yet, whether bFGF affects the development of GC is less studied. METHODS:
      MicroRNA assays, real-time PCR, and western blot were conducted for expression
      analysis of miR-195-5p and basic fibroblast growth factor (bFGF). Luciferase
      activity was measured with mutated bFGF 3'-UTR sequence at the 3' end of the
      luciferase gene. Two GC cell lines, SNU-1 and KATO-3 overexpressing miR-195-5p
      and bFGF were subjected to wound healing assay and transwell invasion assay.
      Mouse GC xenograft model was established and subjected to tumor size analysis.
      RESULTS: Expression levels of miR-195-5p and bFGF showed negative correlation in
      human GC tissues. MiR-195-5p directly targeted bFGF 3'-UTR as demonstrated by
      luciferase activity assay. MiR-195-5p, through downregulating bFGF, inhibited the
      migration and invasion of SNU-1 and KATO-3 cells, as well as tumorigenesis in a
      xenograft mouse model, which could be restored by re-introduction of bFGF.
      CONCLUSIONS: MiR-195-5p inhibits tumorigenesis of GC through suppressing bFGF,
      which supports both miR-195-5p and bFGF as potential therapeutic targets in the
      treatment of GC.

PMID- 28500363
TI  - Diffusion-weighted imaging of the kidneys in haemolytic uraemic syndrome.
AB  - OBJECTIVES: To evaluate the kidneys of patients with haemolytic uraemic syndrome
      (HUS) using diffusion-weighted imaging (DWI) and Doppler ultrasound (US) compared
      with healthy controls. MATERIALS AND METHODS: Fifteen patients (mean age 33.3
      years; three male; 12 female) with diarrhoea-positive HUS and 15 healthy
      volunteers were prospectively evaluated with DWI and Doppler US. A total apparent
      diffusion coefficient (ADCTOT), and ADCs predominantly reflecting microperfusion
      (ADCLOW) and diffusion (ADCHIGH) were calculated. Doppler US evaluated renal
      vascularity and flow. RESULTS: When compared with controls, kidneys affected by
      HUS showed reduced cortical ADC values (ADCTOT 1.79+/-0.22 vs. 2.04+/-0.1x10-3
      mm2/s, P 0.001), resulting in either low corticomedullary differences (11/15
      patients) or an inverted corticomedullary pattern (4/15 patients). Reduction of
      cortical ADC values was associated with a decrease of cortical vascularity on
      Doppler US (ADCTOT, P<0.001; ADCLOW, P 0.047). Kidneys with complete absence of
      the cortical vasculature on Doppler US (four patients) also demonstrated limited
      diffusion (ADCHIGH, P 0.002). Low glomerular filtration rate, requirement for
      haemodialysis during hospitalization, and longer duration of haemodialysis were
      associated with decreased cortical diffusivity (ADCTOT: P 0.04, 0.007, and
      <0.001, respectively). CONCLUSION: DWI shows qualitative and quantitative
      abnormalities in kidneys affected by HUS, thereby extending the non-invasive
      assessment of renal parenchymal damage. KEY POINTS: * In HUS, DWI is feasible for
      functional characterization of kidney involvement. * Kidneys affected by HUS
      showed reduced cortical diffusivity. * Decreased cortical diffusivity was
      associated with lower kidney function. * Requirement and duration of
      haemodialysis was linked to degree of cortical alterations.

PMID- 28500364
TI  - Radiologists need to be aware of secondary central venous stenosis in patients
      with SAPHO syndrome.
AB  - OBJECTIVES: We aimed to define central venous stenosis (CVS) caused by
      sternocostoclavicular hyperostosis as a feature of synovitis-acne-pustulosis
      hyperostosis-osteitis (SAPHO) syndrome on routine contrast-enhanced computed
      tomography (CT) images. The relationship between SAPHO syndrome and CVS without
      venous thrombosis caused by anterior chest wall compression has not been
      investigated. Therefore, the present study evaluated CVS in patients with SAPHO
      syndrome at our hospital. METHODS: We retrospectively reviewed contrast-enhanced
      CT images of ten patients with suspected or diagnosed SAPHO syndrome between
      January 2007 and November 2015. The patients were assessed by contrast-enhanced
      CT using 16-, 64- or 128-detector row scanners. Two radiologists independently
      assessed the presence of CVS or obstruction and SAPHO syndrome in a retrospective
      review of CT images. RESULTS: Six of the ten patients had findings of CVS with
      SAPHO syndrome. The mean diameter and patency rate at the site of CVS were 1.88
      mm and 27.2%, respectively. Stenosis was more significant in terms of the mean
      diameter of CVS sites than of stenotic sites that crossed the anteroposterior
      vein (p < 0.05). CONCLUSIONS: Radiologists who routinely assess contrast-enhanced
      CT images should be aware that sternocostoclavicular hyperostosis with SAPHO
      syndrome could cause secondary CVS. KEY POINTS: * SAPHO syndrome can cause
      central venous stenosis. * Radiologists should consider central venous stenosis
      in patients with SAPHO syndrome. * Early diagnosis of central venous stenosis due
      to SAPHO syndrome is challenging.

PMID- 28500365
TI  - Capsule, septum, and T2 hyperintense foci for differentiation between large
      hepatocellular carcinoma (>=5 cm) and intrahepatic cholangiocarcinoma on
      gadoxetic acid MRI.
AB  - OBJECTIVE: To determine the added value of capsule, septum, and T2 hyperintense
      foci for differentiating large hepatocellular carcinoma (HCC; >= 5 cm) from
      intrahepatic cholangiocarcinoma (ICC) using gadoxetic acid MRI. METHODS: The
      study included 116 patients (94 men, 22 women; mean age, 56.8 years) with
      surgically confirmed HCCs (n = 87, 5.0-18.0 cm) or ICCs (n = 29, 5.0-14.0 cm) who
      underwent gadoxetic acid MRI. Three observers independently reviewed MRIs in two
      sessions, examining enhancement patterns only and then adding capsule, septum,
      and T2 hyperintense foci. Reviewers used a five-point scale to score accuracy,
      sensitivity, and specificity. RESULTS: A significant increase was observed in
      accuracy when ancillary features (96.1-98.3%) were added compared to enhancement
      pattern only (83.6-88.4%; p <= 0.02). Sensitivity was significantly increased
      with combined reading (97.1-98.3%) compared to enhancement features only (81.6
      88.5%; p <= 0.006) for two observers, with no difference in specificity (84.5
      89.7% vs. 86.2-98.3%; p > 0.05). We found substantial to excellent interobserver
      agreement for ancillary features (0.598-0.976). CONCLUSION: Adding capsule,
      septum, and T2 hyperintense foci to enhancement patterns for gadoxetic acid MRI
      increased diagnostic performance for characterizing large HCC by differentiating
      it from ICC. KEY POINTS: * Capsule, septum, and T2 hyperintense foci were useful
      for characterizing large HCC. * Adding ancillary features to enhancement pattern
      increased accuracy for diagnosing large HCC. * Interobserver agreement was
      substantial to excellent for ancillary features.

PMID- 28500366
TI  - Comparison of 3D magnetic resonance imaging and digital subtraction angiography
      for intracranial artery stenosis.
AB  - OBJECTIVES: To compare three-dimensional high-resolution magnetic resonance
      imaging (3D HR-MRI) and digital subtraction angiography (DSA) for diagnosing and
      evaluating stenosis in the entire circle of Willis. METHODS: The study included
      516 intracranial arteries from 43 patients with intracranial artery stenosis
      (ICAS) who underwent both 3D HR-MRI and DSA within 1 month. Two readers
      independently diagnosed atherosclerosis, dissection, moyamoya disease and
      vasculitis, rated their diagnostic confidence for each vessel and measured the
      luminal diameters. Reference standard was made from clinico-radiologic diagnosis.
      Diagnostic accuracy, diagnostic confidence, the degree of stenosis and luminal
      diameter were assessed and compared between both modalities. RESULTS: For
      atherosclerosis, 3D HR-MRI showed better diagnostic accuracy (P = .03-.003),
      sensitivity (P = .006-.01) and positive predictive value (P <= .001-.006)
      compared to DSA. Overall, the readers were more confident of their diagnosis of
      ICAS when using 3D HR-MRI (reader 1, P <= .001-.007; reader 2, P <= .001-.015).
      3D HR-MRI showed similar degree of stenosis (P > .05) and higher luminal diameter
      (P < .05) compared to DSA. CONCLUSIONS: 3D HR-MRI might be useful to evaluate
      atherosclerosis, with better diagnostic confidence and comparable stenosis
      measurement compared to DSA in the entire circle of Willis. KEY POINTS: * 3D HR
      MRI showed better diagnostic accuracy for atherosclerosiscompared to DSA * 3D HR
      MRI showed better overall diagnostic confidence for stenosiscompared to DSA * 3D
      HR-MRI and DSA showed similar degree of stenosis.

PMID- 28500367
TI  - Evolution of posterior fossa and brain morphology after in utero repair of open
      neural tube defects assessed by MRI.
AB  - OBJECTIVES: To describe characteristics of foetuses undergoing in utero repair of
      open neural tube defects (ONTD) and assess postoperative evolution of posterior
      fossa and brain morphology. METHODS: Analysis of pre- and postoperative foetal as
      well as neonatal MRI of 27 foetuses who underwent in utero repair of ONTD. Type
      and level of ONTD, hindbrain configuration, posterior fossa and liquor space
      dimensions, and detection of associated findings were compared between MRI
      studies and to age-matched controls. RESULTS: Level of bony spinal defect was
      defined with exactness of +/- one vertebral body. Of surgically confirmed 18
      myelomeningoceles (MMC) and 9 myeloschisis (MS), 3 MMC were misdiagnosed as MS
      due to non-visualisation of a flat membrane on MRI. Hindbrain herniation was more
      severe in MS than MMC (p < 0.001). After repair, hindbrain herniation resolved in
      25/27 cases at 4 weeks and liquor spaces increased. While posterior fossa
      remained small (p < 0.001), its configuration normalised. Lateral ventricle
      diameter indexed to cerebral width decreased in 48% and increased in 12% of
      cases, implying a low rate of progressive obstructive hydrocephalus. Neonatally
      evident subependymal heterotopias were detected in 33% at preoperative and 50% at
      postoperative foetal MRI. CONCLUSION: MRI demonstrates change of Chiari
      malformation type II (CM-II) features. KEY POINTS: * Hindbrain herniation is
      significantly more pronounced in myeloschisis than in myelomeningocele *
      Resolution of hindbrain herniation 4 weeks after in utero closure of ONTD * MRI
      is valuable for preoperative assessment and postoperative evaluation following in
      utero repair.

PMID- 28500368
TI  - Advanced myocardial tissue characterisation by a multi-component CMR protocol in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering
      from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR)
      mapping techniques might be appropriate tools to complement late gadolinium
      enhancement (LGE) for the assessment of myocardial involvement. This study aimed
      to perform advanced myocardial tissue characterisation in RA patients by a
      multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled
      and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers
      served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA
      patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded
      extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49
      ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2
      mapping showed the highest prevalence of values beyond the 95% percentile of
      controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values
      compared to controls, with most significant differences for T2. Since these
      results seem to be independent of the presence of LGE, advanced myocardial tissue
      characterisation including CMR mapping techniques in addition to LGE-CMR might be
      useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: *
      RA patients had higher T1, ECV and T2 values compared to controls. * Most
      significant differences were observed for T2. * Our results seem to be
      independent of the presence of LGE. * Mapping might be useful in the evaluation
      of myocardial involvement in RA.

PMID- 28500369
TI  - Feature-tracking myocardial strain analysis in acute myocarditis: diagnostic
      value and association with myocardial oedema.
AB  - OBJECTIVES: To investigate the diagnostic value of cardiac magnetic resonance
      (CMR) feature-tracking (FT) myocardial strain analysis in patients with suspected
      acute myocarditis and its association with myocardial oedema. METHODS: Forty
      eight patients with suspected acute myocarditis and 35 control subjects underwent
      CMR. FT CMR analysis of systolic longitudinal (LS), circumferential (CS) and
      radial strain (RS) was performed. Additionally, the protocol allowed for the
      assessment of T1 and T2 relaxation times. RESULTS: When compared with healthy
      controls, myocarditis patients demonstrated reduced LS, CS and RS values (LS: 
      19.5 +/- 4.4% vs. -23.6 +/- 3.1%, CS: -23.0 +/- 5.8% vs. -27.4 +/- 3.4%, RS: 28.9
      +/- 8.5% vs. 32.4 +/- 7.4%; P < 0.05, respectively). LS (T1: r = 0.462, P <
      0.001; T2: r = 0.436, P < 0.001) and CS (T1: r = 0.429, P < 0.001; T2: r = 0.467,
      P < 0.001) showed the strongest correlations with T1 and T2 relaxations times.
      Area under the curve of LS (0.79) was higher compared with those of CS (0.75; P =
      0.478) and RS (0.62; P = 0.008). CONCLUSIONS: FT CMR myocardial strain analysis
      might serve as a new tool for assessment of myocardial dysfunction in the
      diagnostic work-up of patients suspected of having acute myocarditis. Especially,
      LS and CS show a sufficient diagnostic performance and were most closely
      correlated with CMR parameters of myocardial oedema. KEY POINTS: * Myocardial
      strain measures are considerably reduced in patients with suspected myocarditis.
      * Myocardial strain measures can sufficiently discriminate between diseased and
      healthy patients. * Myocardial strain measures show basic associations with the
      extent of myocardial oedema/inflammation.

PMID- 28500371
TI  - The silhouette technique: improving post-operative radiographs for planning of
      correction with a hexapod external fixator.
AB  - Correction of deformity of a bone through use of a hexapod external fixator
      requires clear definition of the relationship between the bone and the frame.
      Achieving adequate orthogonal calibrated radiographs for this aim, with minimum X
      ray exposure, can prove a challenge in the radiography suite. We describe a
      simple technique for obtaining adequate imaging, without the use of additional
      equipment. Introduction of the technique to our department has demonstrated an
      improvement in the adequacy of planning radiographs and a reduction in the
      requirement for repeat imaging.

PMID- 28500370
TI  - Long-term prognostic performance of low-dose coronary computed tomography
      angiography with prospective electrocardiogram triggering.
AB  - OBJECTIVES: To assess long-term prognosis after low-dose 64-slice coronary
      computed tomography angiography (CCTA) using prospective electrocardiogram
      triggering. METHODS: We included 434 consecutive patients with suspected or known
      coronary artery disease referred for low-dose CCTA. Patients were classified as
      normal, with non-obstructive or obstructive lesions, or previously
      revascularized. Coronary artery calcium score (CACS) was assessed in 223
      patients. Follow-up was obtained regarding major adverse cardiac events (MACE):
      cardiac death, myocardial infarction and elective revascularization. We performed
      Kaplan-Meier analysis and Cox regressions. RESULTS: Mean effective radiation dose
      was 1.7 +/- 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non
      obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty
      nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 +/-
      0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non
      obstructive lesions, 30% with obstructive stenosis and 39% of those
      revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but
      4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression
      identified obstructive stenosis, lesion burden in CCTA and CACS as independent
      MACE predictors (P <= 0.001). CONCLUSION: Low-dose CCTA with prospective
      electrocardiogram-triggering has an excellent long-term prognostic performance
      with a warranty period >6 years for patients with normal coronary arteries. KEY
      POINTS: * Coronary CT angiography (CCTA) has an excellent long-term prognostic
      performance. * CCTA can accurately stratify cardiac risk according to coronary
      lesion severity. * A normal CCTA predicts freedom from cardiac events for >6
      years. * Patients with a coronary calcium score of 0 may experience cardiac
      events. * CCTA allows for reclassification of cardiac risk compared with ESC
      SCORE.

PMID- 28500372
TI  - Ion mobility-mass spectrometry as a tool to investigate protein-ligand
      interactions.
AB  - Ion mobility-mass spectrometry (IM-MS) is a powerful tool for the simultaneous
      analysis of mass, charge, size, and shape of ionic species. It allows the
      characterization of even low-abundant species in complex samples and is therefore
      particularly suitable for the analysis of proteins and their assemblies. In the
      last few years even complex and intractable species have been investigated
      successfully with IM-MS and the number of publications in this field is steadily
      growing. This trend article highlights recent advances in which IM-MS was used to
      study protein-ligand complexes and in particular focuses on the catch and release
      (CaR) strategy and collision-induced unfolding (CIU). Graphical Abstract Native
      mass spectrometry and ion mobility-mass spectrometry are versatile tools to
      follow the stoichiometry, energetics, and structural impact of protein-ligand
      binding.

PMID- 28500373
TI  - Effects of varenicline versus transdermal nicotine replacement therapy on
      cigarette demand on quit day in individuals with substance use disorders.
AB  - RATIONALE: Cigarette demand is a behavioral economic measure of the relative
      value of cigarettes. Decreasing the value of cigarette reinforcement may help
      with quitting smoking. OBJECTIVES: This study aimed to evaluate the effects of
      initial use of varenicline (VAR) versus nicotine replacement therapy (NRT) on
      demand for cigarettes on quit day among smokers with substance use disorders
      (SUD) and to determine whether reduced demand was associated with subsequent
      abstinence from smoking at 1 and 3 months. METHODS: Participants (N = 110) were
      randomized to double-blind, double-placebo conditions: VAR with placebo NRT or
      NRT with placebo capsules. The cigarette purchase task (CPT) was used to assess
      demand for cigarettes at baseline and on quit day, following a 1-week medication
      dose run-up/placebo capsule lead-in and first day use of the patch. RESULTS:
      Demand for cigarettes decreased from baseline to quit day without significant
      differences between medications. Reductions in CPT intensity (number of
      cigarettes that would be smoked if they were free) and CPT breakpoint (lowest
      price at which no cigarettes would be purchased) predicted greater likelihood of
      abstaining on quit day. Reduced intensity predicted length of abstinence at 1 and
      3 months while reduced breakpoint predicted only 1 month length of abstinence.
      CONCLUSIONS: Initial therapeutic doses of VAR and NRT resulted in similar
      reductions in cigarette reinforcement. Larger initial reductions in demand on
      quit day were associated with early success with abstaining from cigarettes.
      Behavioral economic approaches may be useful for identifying individuals who
      benefit less from pharmacotherapy and may need additional treatment resources.
      TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00756275.

PMID- 28500374
TI  - Exploring the genetics of feed efficiency and feeding behaviour traits in a pig
      line highly selected for performance characteristics.
AB  - The consideration of feed efficiency traits is highly relevant in animal breeding
      due to economic and ecologic impacts of the efficient usage and utilization of
      feed resources. In pigs, corresponding observations are recorded using automatic
      feeding stations and serve as one of the main criteria in most pig selection
      programmes. Simultaneously, feeding stations also generate feeding behaviour data
      which represent a nearly unused resource and provide a valuable proxy measure of
      health status, animal welfare, and management practices. In the current study, an
      integrated approach was applied to a feed efficiency tested and genome-wide
      genotyped terminal sire line population. Therefore, genetic analyses were
      performed combining a single-marker based approach and a Bayesian multi-marker
      algorithm. Major quantitative trait loci (QTL) for feeding behaviour traits
      comprising daily occupation time, daily feeder visit, and daily feeding rate were
      identified on chromosomes 1, 4, 6, 7, 8, and 14. Feed efficiency was represented
      by feed conversion ratio and daily feed intake revealing prominent genomic
      regions on chromosomes 1, 6, 9, and 11. The positional and functional candidate
      genes identified are involved in transport processes like AQP4, SLC22A23, and
      SLC6A14 as well as energy sensing, generation, and utilization as exemplified by
      PPP3CA, IQGAP3, ECI2, and DnaJC15. These molecular features provide the first
      step towards the dissection of the genetic connection between distinct feeding
      behaviour patterns, feed efficiency and performance, health, and welfare traits
      driving the implementation of these traits in breeding programmes and pig
      husbandry.

PMID- 28500375
TI  - First molecular identification and genetic diversity of Strongyloides stercoralis
      and Strongyloides fuelleborni in human communities having contact with long
      tailed macaques in Thailand.
AB  - The parasitic nematodes, Strongyloides stercoralis and Strongyloides fuelleborni,
      can infect humans and non-human primates. We amplified and sequenced a portion of
      the 18S ribosomal RNA gene (rRNA) and of the mitochondrial cytochrome c oxidase
      subunit 1 (cox1) gene of Strongyloides from humans in the study area in Thailand,
      where people have frequent contact with long-tailed macaques. Fresh stool samples
      were obtained from 213 people and were examined using the agar plate culture
      method. The overall prevalence of Strongyloides infection was 8.92% (19/213).
      From a total of 19 worms (one per infected person), 18 adult males had 18S rRNA
      sequences identical with that of S. stercoralis and one adult female had a
      sequence almost identical with that of S. fuelleborni. A median-joining network
      of cox1 sequences revealed nine new haplotypes from S. stercoralis, and an
      overall haplotype diversity (Hd) of 0.9309. The single haplotype of S.
      fuelleborni was also new and contributed to an overall haplotype diversity for
      that species of 0.9842. This is the first molecular identification of S.
      stercoralis and S. fuelleborni in a human community having contact with long
      tailed macaques in Thailand. It is also the first report of S. fuelleborni
      infecting a human in Thailand.

PMID- 28500376
TI  - The PTPN22 R263Q polymorphism confers protection against systemic lupus
      erythematosus and rheumatoid arthritis, while PTPN22 R620W confers susceptibility
      to Graves' disease in a Mexican population.
AB  - OBJECTIVE: The functional PTPN22 R620W polymorphism (rs2476601) is clearly
      associated with susceptibility to several autoimmune diseases (ADs). However, the
      PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different
      ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q
      polymorphisms with susceptibility to or protection against rheumatoid arthritis
      (RA), systemic lupus erythematosus (SLE), and Graves' disease (GD) among Mexican
      patients. METHODS: We conducted a case-control study including 876 patients (405
      with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals.
      PTPN22 genotypes were determined using the TaqMan 5' allele discrimination assay.
      RESULTS: PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004),
      but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated
      that this polymorphism is associated with RA susceptibility (OR 4.17, p =
      0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR
      0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.
      CONCLUSIONS: Our data provide the first demonstration that PTPN22 R620W confers
      GD susceptibility among Latin-American patients. Moreover, this is the second
      report documenting the association of PTPN22 R263Q with protection against SLE
      and RA.

PMID- 28500377
TI  - Reliability of echocardiographic speckle-tracking derived bi-atrial strain
      assessment under different hemodynamic conditions.
AB  - The aim of this study was to assess intra- and inter-observer variability of left
      (LA) and right atrial (RA) strain indices obtained by two-dimensional speckle
      tracking echocardiography (2D-STE) in a healthy group of individuals at low
      altitude and after rapid ascent to high-altitude in order to provoke altered
      systemic and pulmonary hemodynamics otherwise seen in various cardiac diseases.
      Twenty healthy subjects underwent transthoracic echocardiography during a
      baseline examination at low-altitude (424 m) as well as 7, 20 and 44 h after
      arrival at high-altitude (4559 m). Atrial strain indices (i.e. reservoir, conduit
      and contractile strain) were determined off-line by two independent observers.
      Intra- and inter-observer reproducibility of variables was assessed by intra
      class correlation coefficients (ICCs), coefficients of variation and Bland Altman
      plots. Heart rate, systemic blood pressure and pulmonary artery pressure
      increased significantly from low-altitude to the first examination at high
      altitude. Intra-observer ICCs were >=0.90 except for RA conduit strain with an
      ICC of 0.86. The mean intra-observer differences were small and limits of
      agreement of relative differences were narrow for all atrial strain parameters
      (<3 and <16%, respectively). Inter-observer ICCs (0.80-0.90), mean biases and
      limits of agreement (<4 and <20%, respectively) were greater than intra-observer
      results for all parameters. Intra- and inter-obserer ICCs for all atrial strain
      variables did not differ between low- and high-altitude. 2D-STE-derived bi-atrial
      strain indices have excellent intra- and moderate inter-observer reproducibility
      with no effect of high-altitude-induced hemodynamic changes on reliability
      results.

PMID- 28500378
TI  - Intravascular ultrasound elastography analysis of the elastic mechanical
      properties of atherosclerotic plaque.
AB  - To assess the elastic mechanical properties of atherosclerotic plaque with
      different morphological properties by intravascular ultrasound elastography
      (IVUSE). 30 purebred New Zealand rabbits were fed a high-cholesterol diet; the
      abdominal aorta endothelium was balloon-injured after 2 weeks; at week 12, 2
      plaques with moderate echo from each rabbit were chosen for in situ imaging, and
      2 consecutive frames near the end-diastole images in situ were used to construct
      an IVUS elastogram. Shear strain (SS) and area strain (AS) were greater for
      eccentric than centripetal plaque (SS: 2.65(2.45)% vs. 1.79 +/- 0.97%, p < 0.05;
      AS: 4.81(4.99)% vs. 3.23 +/- 1.75%, p < 0.05) but were lower with low than high
      plaque burden (SS: 2.14 +/- 0.37% vs. 3.40 +/- 0.34%, p < 0.05; AS: 3.88 +/-
      0.60% vs. 5.81 +/- 0.54%, p < 0.05). SS and AS were significantly greater for
      plaque with negative than no remodeling (SS: 3.98 +/- 1.53% vs. 1.82(1.40)%, p <
      0.017; AS: 6.94 +/- 2.24% vs. 2.59(2.87)%, p < 0.017) and were found correlated
      with eccentric index and plaque burden (R2 = 0.365 and R2 = 0.359, both p <
      0.05). Plaques associated with eccentricity, high plaque burden and negative
      remodeling showed greater strain than those with centripetalism, low plaque
      burden and positive remodeling. Eccentric index and plaque burden may be useful
      to predict the elastic stability of plaque.

PMID- 28500380
TI  - Association of T lymphocyte immune imbalance and IL-10 gene polymorphism with the
      risk of obstructive sleep apnea in children with obesity.
AB  - PURPOSE: The purpose of this study is to determine the role of T lymphocyte
      immune imbalance and interleukin (IL)-10 gene polymorphism in the development of
      obstructive sleep apnea (OSA) in obese children. METHODS: One hundred obese
      children at high-risk and low-risk for OSA based upon a sleep questionnaire were
      selected. Peripheral blood T lymphocyte subsets were measured by flow cytometry,
      and plasma IFN-gamma, IL-4, and IL-10 cytokines were detected by ELISA. The
      relationships between OSA and the above variables were analyzed. IL-10 gene
      polymorphisms were analyzed by DNA sequencing. RESULTS: Ninety subjects completed
      all the tests. Forty-two patients were diagnosed as OSA by PSG. Compared with non
      OSA children, the levels of CD4+ T cells, IFN-gamma, and IL-4 were increased (P <
      0.05) whereas the numbers of CD4+ CD25+ Treg and NKT cells and the levels of IL
      10 were reduced (P < 0.05). Multiple linear regression analysis showed that IL-10
      level was negatively associated with OAHI (OR 0.352, 95% CI 0.286-0.540; P <
      0.05). In multivariate analysis, IL-10 also had a strong negative association
      with OSA after adjustment for confounding factors from models 1 to 3. Correlative
      analysis showed that IL-10 levels had a positive association with CD4+ CD25+ Treg
      (r = 0.628, P < 0.01). Furthermore, the IL-10/A-1082G gene polymorphism
      correlated with OSA. CONCLUSIONS: T lymphocyte immune imbalance was associated
      with OSA and IL-10 may play an important protective role in the pathogenesis of
      OSA in obese children.

PMID- 28500379
TI  - Effect of zinc deprivation on the lipid metabolism of budding yeast.
AB  - Zinc is an essential micronutrient for all living cells. It serves as a
      structural and catalytic cofactor for numerous proteins, hence maintaining a
      proper level of cellular zinc is essential for normal functioning of the cell.
      Zinc homeostasis is sustained through various ways under severe zinc-deficient
      conditions. Zinc-dependent proteins play an important role in biological systems
      and limitation of zinc causes a drastic change in their expression. In budding
      yeast, a zinc-responsive transcription factor Zap1p controls the expression of
      genes required for uptake and mobilization of zinc under zinc-limiting
      conditions. It also regulates the polar lipid levels under zinc-limiting
      conditions to maintain membrane integrity. Deletion of ZAP1 causes an increase in
      triacylglyerol levels which is due to the increased biosynthesis of acetate that
      serves as a precursor for triacylglycerol biosynthesis. In this review, we
      expanded our recent work role of Zap1p in nonpolar lipid metabolism of budding
      yeast.

PMID- 28500381
TI  - Radical change or warm sentiments? A commentary on Gronholm et al. (2017)
      Interventions to reduce discrimination and stigma: the state of the art.

PMID- 28500382
TI  - The football sign.

PMID- 28500383
TI  - Quantitative assessment of the degree of differentiation in colon cancer with
      dual-energy spectral CT.
AB  - OBJECTIVE: To evaluate dual-energy spectral CT imaging in evaluating the degree
      of differentiation in colon cancer. METHODS: Forty-seven colon cancer patients
      underwent spectral CT during arterial phase (AP) and portal venous phase (PP),
      and were characterized pathologically differentiated to well-differentiated (A, n
      = 18) and poorly differentiated or undifferentiated carcinoma group (B, n = 29).
      Lesion iodine concentration (IC) was measured and normalized to that of aorta
      (NIC). CT numbers were measured and the slope (lambda HU) of the spectral HU
      curve was calculated. These parameters were statistically compared between the
      two groups. ROC curves were used to evaluate their diagnostic efficacies.
      RESULTS: There were significant differences in IC (1.01 +/- 0.20 vs. 1.59 +/-
      0.57 mg/ml), NIC (0.12 +/- 0.03 vs. 0.19 +/- 0.09), lambda HU (1.41 +/- 0.29 vs.
      2.03 +/- 0.85), and CT number at 70 keV (48.61 +/- 9.03HU vs. 63.97 +/- 15.86HU)
      between groups A and B in AP (p < 0.05), but no difference in PP. Using IC = 1.13
      mg/ml in AP as the threshold, one obtained a sensitivity of 81.8% and a
      specificity of 71.4% for differentiating well-differentiated from poorly
      differentiated or undifferentiated carcinoma. These values were statistically
      higher than those (64.7% and 62.3%) using CT number at 70 keV. CONCLUSION:
      Spectral CT imaging parameters (IC, NIC, and lambda HU) in AP provide improved
      accuracy for evaluating the degrees of differentiation in colon cancer than CT
      number at 70 keV.

PMID- 28500385
TI  - Assessment of the horizontal transfer of functional genes as a suitable approach
      for evaluation of the bioremediation potential of petroleum-contaminated sites: a
      mini-review.
AB  - Petroleum sludge contains recalcitrant residuals. These compounds because of
      being toxic to humans and other organism are of the major concerns. Therefore,
      petroleum sludge should be safely disposed. Physicochemical methods which are
      used by this sector are mostly expensive and need complex devices. Bioremediation
      methods because of being eco-friendly and cost-effective overcome most of the
      limitations of physicochemical treatments. Microbial strains capable to degrade
      petroleum hydrocarbons are practically present in all soils and sediments and
      their population density increases in contact with contaminants. Bacterial
      strains cannot degrade alone all kinds of petroleum hydrocarbons, rather
      microbial consortium should collaborate with each other for degradation of
      petroleum hydrocarbon mixtures. Horizontal transfer of functional genes between
      bacteria plays an important role in increasing the metabolic potential of the
      microbial community. Therefore, selecting a suitable degrading gene and tracking
      its horizontal transfer would be a useful approach to evaluate the bioremediation
      process and to assess the bioremediation potential of contaminated sites.

PMID- 28500384
TI  - Associations between social vulnerabilities and psychosocial problems in European
      children. Results from the IDEFICS study.
AB  - The effect of socioeconomic inequalities on children's mental health remains
      unclear. This study aims to explore the cross-sectional and longitudinal
      associations between social vulnerabilities and psychosocial problems, and the
      association between accumulation of vulnerabilities and psychosocial problems.
      5987 children aged 2-9 years from eight European countries were assessed at
      baseline and 2-year follow-up. Two different instruments were employed to assess
      children's psychosocial problems: the KINDL (Questionnaire for Measuring Health
      Related Quality of Life in Children and Adolescents) was used to evaluate
      children's well-being and the Strengths and Difficulties Questionnaire (SDQ) was
      used to evaluate children's internalising problems. Vulnerable groups were
      defined as follows: children whose parents had minimal social networks, children
      from non-traditional families, children of migrant origin or children with
      unemployed parents. Logistic mixed-effects models were used to assess the
      associations between social vulnerabilities and psychosocial problems. After
      adjusting for classical socioeconomic and lifestyle indicators, children whose
      parents had minimal social networks were at greater risk of presenting
      internalising problems at baseline and follow-up (OR 1.53, 99% CI 1.11-2.11). The
      highest risk for psychosocial problems was found in children whose status changed
      from traditional families at T0 to non-traditional families at T1 (OR 1.60, 99%
      CI 1.07-2.39) and whose parents had minimal social networks at both time points
      (OR 1.97, 99% CI 1.26-3.08). Children with one or more vulnerabilities
      accumulated were at a higher risk of developing psychosocial problems at baseline
      and follow-up. Therefore, policy makers should implement measures to strengthen
      the social support for parents with a minimal social network.

PMID- 28500386
TI  - Thermodynamics of enzyme-catalyzed esterifications: I. Succinic acid
      esterification with ethanol.
AB  - Succinic acid (SA) was esterified with ethanol using Candida antarctica lipase B
      immobilized on acrylic resin at 40 and 50  degrees C. Enzyme activity in the
      reaction medium was assured prior to reaction experiments. Reaction-equilibrium
      experiments were performed for varying initial molalities of SA and water in the
      reaction mixtures. This allowed calculating the molality-based apparent
      equilibrium constant K m as function of concentration and temperature. K m was
      shown to depend strongly on the molality of water and SA as well as on
      temperature. It could be concluded that increasing the molality of SA shifted the
      reaction equilibrium towards the products. Water had a strong effect on the
      activity of the enzyme and on K m . The concentration dependence of K m values
      was explained by the activity coefficients of the reacting agents. These were
      predicted with the thermodynamic models Perturbed-Chain Statistical Associating
      Fluid Theory (PC-SAFT), NRTL, and Universal Quasichemical Functional Group
      Activity Coefficients (UNIFAC), yielding the ratio of activity coefficients of
      products and reactants K gamma . All model parameters were taken from literature.
      The models yielded K gamma values between 25 and 115. Thus, activity coefficients
      have a huge impact on the consistent determination of the thermodynamic
      equilibrium constants K th. Combining K m and PC-SAFT-predicted K gamma allowed
      determining K th and the standard Gibbs energy of reaction as function of
      temperature. This value was shown to be in very good agreement with results
      obtained from group contribution methods for Gibbs energy of formation. In
      contrast, inconsistencies were observed for K th using K gamma values from the
      classical gE-models UNIFAC and NRTL. The importance of activity coefficients
      opens the door for an optimized reaction setup for enzymatic esterifications.

PMID- 28500387
TI  - Thermal adaptation strategies of the extremophile bacterium Thermus filiformis
      based on multi-omics analysis.
AB  - Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot
      spring in New Zealand. The experimental study of the mechanisms of thermal
      adaptation is important to unveil response strategies of the microorganism to
      stress. In this study, the main pathways involved on T. filiformis
      thermoadaptation, as well as, thermozymes with potential biotechnological
      applications were revealed based on omics approaches. The strategy adopted in
      this study disclosed that pathways related to the carbohydrate metabolism were
      affected in response to thermoadaptation. High temperatures triggered oxidative
      stress, leading to repression of genes involved in glycolysis and the
      tricarboxylic acid cycle. During heat stress, the glucose metabolism occurred
      predominantly via the pentose phosphate pathway instead of the glycolysis
      pathway. Other processes, such as protein degradation, stringent response, and
      duplication of aminoacyl-tRNA synthetases, were also related to T. filiformis
      thermoadaptation. The heat-shock response influenced the carotenoid profile of T.
      filiformis, favoring the synthesis of thermozeaxanthins and thermobiszeaxanthins,
      which are related to membrane stabilization at high temperatures. Furthermore,
      antioxidant enzymes correlated with free radical scavenging, including superoxide
      dismutase, catalase and peroxidase, and metabolites, such as oxaloacetate and
      alpha-ketoglutarate, were accumulated at 77  degrees C.

PMID- 28500388
TI  - Aspergillus atacamensis and A. salisburgensis: two new halophilic species from
      hypersaline/arid habitats with a phialosimplex-like morphology.
AB  - Halophilic fungal strains isolated from historical wooden staircase in a salt
      mine in Austria, and from wall biofilm and soil of a cave in the Coastal Range of
      the hyperarid Atacama Desert in Chile were characterised and described newly as
      Aspergillus salisburgensis and Aspergillus atacamensis. Morphological characters
      including solitary phialides producing solitary conidia and conidia in chains
      and/or heads suggested affinity to Aspergillus subgenus Polypaecilum. Strains
      required salt for growth, grew optimally on media with 10-25% NaCl and at 15-28 
      degrees C. These values are similar to those observed for Aspergillus salinarus
      comb. nov. (Phialosimplex salinarum), while the ex-type strains of Aspergillus
      sclerotialis, Aspergillus chlamydosporus and Aspergillus caninus (all belonging
      to Aspergillus subgen. Polypaecilum) grew optimally at 0-5% NaCl and showed
      fastest growth at 28-37  degrees C. Phylogenetic analyses on the basis of rDNA
      sequences, RAPD-PCR fingerprint patterns, and cellobiohydrolase gene (cbh-I)
      polymorphism clustered the strains into three groups and supported their
      taxonomic recognition as A. salinarus, A. atacamensis and A. salisburgensis. On
      the basis of phylogenetic inferences, also Sagenomella keratitidis is newly
      combined as Aspergillus keratitidis and inferred as a species of Aspergillus
      subgenus Polypaecilum.

PMID- 28500389
TI  - Degradation of phospholipids under different types of irradiation and varying
      oxygen saturation.
AB  - The effects of different types of radiation on the formation of peroxide forms of
      2-dioleoyl-sn-glycero-3-phosphocholine were studied under various conditions. For
      the irradiation, an aqueous solution of small unilamellar vesicles was prepared.
      Variations in parameters such as the dose rate and molecular oxygen saturation
      levels were evaluated. Our study suggests that the mechanism of the peroxides
      formation process remains unchanged under irradiation by accelerated electrons,
      gamma and accelerated protons. The values of radiation chemical yields of the
      peroxidic form depend on the type of radiation, dose rate, and the saturation of
      molecular oxygen. The level of oxygen saturation strongly affects the values of
      radiation chemical yields as well, as the dissolved oxygen is an important agent
      participating in peroxidation and it is a source of free radicals during the
      radiolysis. The values of radiation chemical yields strongly suggest that the
      mechanism of radiation-induced peroxidation of phosphatidylcholines does not
      proceed via chain reaction.

PMID- 28500391
TI  - Anterior referencing of tibial slope in total knee arthroplasty considerably
      influences knee kinematics: a musculoskeletal simulation study.
AB  - PURPOSE: In total knee arthroplasty (TKA), the posterior tibial slope is not
      always reconstructed correctly, and the knee ligaments may become too tight in
      flexion. To release a tight flexion gap, surgeons can increase the posterior
      tibial slope using two surgical resection techniques: the anterior tibial cortex
      (ACR) or the centre of tibial plateau (CPR) referencing. It is not known how this
      choice affects the knee laxity and function during activities of daily living.
      The aim of this study was to investigate the effect of tibial slope on knee
      laxity, kinematics and forces during a squatting activity using computer
      simulation techniques. We hypothesised that the effects depend on the referencing
      technique utilised. METHODS: A validated musculoskeletal model of TKA was used.
      Knee laxity tests were simulated in flexion and extension. Then, a squat motion
      was simulated to calculate: movement of the tibiofemoral joint (TFJ) contact
      points and patello-femoral joint (PFJ) contact force. All analyses were repeated
      with more anterior (-3 degrees ), neutral (0 degrees ), and more posterior tibial
      slope (+3 degrees , +6 degrees , +9 degrees ), and with two referencing
      techniques (ACR, CPR). RESULTS: Knee laxities increased dramatically with more
      posterior slope with the ACR technique (up to 400%), both in flexion and in
      extension. The CPR technique, instead, had much smaller effects (up to 42%
      variations). During squatting, more slope with the ACR technique resulted in
      larger movements of the TFJ contact point. The PFJ contact force decreased
      considerably with more slope with the CPR technique (12% body weight reduction
      every 3 degrees  more posterior slope), thanks to the preservation of the
      patellar height and quadriceps-femur load sharing. CONCLUSION: ACR technique
      alters considerably the knee laxity, both in flexion and extensions, and surgeons
      should be cautious about its use. More slope with CPR technique induces more
      favourable TFJ kinematics and loading of the knee extensor apparatus and does not
      substantially alter knee laxity. Preferably, the tibial slope resection should be
      pre-planned thoroughly and performed using CPR technique as accurately as
      possible. Surgeons can directly translate the results of this study into the
      clinical practice.

PMID- 28500392
TI  - A case of advanced gastric cancer achieved a pathological complete response by
      chemotherapy.
AB  - BACKGROUND: Although chemotherapy is the first recommended treatment of
      unresectable gastric cancer, a pathological complete response is a rare event.
      CASE PRESENTATION: A 58-year-old male was diagnosed as gastric cancer with a
      bulky tumor, lymphadenopathy, and suspicious peritoneal dissemination. The
      patient underwent chemotherapy with S-1 and cisplatin. After three courses of
      chemotherapy, a computed tomography showed dramatic improvements in gastric wall
      thickening, shrinkage of lymphadenopathy, and disappearance of disseminated
      peritoneal lesion. The patient underwent potentially curative resection by total
      gastrectomy with D2 lymph node dissection. Histological examination revealed the
      absence of malignant cells not only in the resected specimen but also in the
      harvested lymph nodes. At present, more than 7 years after the initial surgery,
      the patient is still alive without any recurrence. CONCLUSIONS: We obtained a
      pathological complete response by chemotherapy with S-1 and cisplatin for
      advanced gastric cancer. Although a pathological complete response is a rare
      event, it would be associated with the long-term survival of patients with
      advanced gastric cancer.

PMID- 28500390
TI  - Pollen exposure and hospitalization due to asthma exacerbations: daily time
      series in a European city.
AB  - Exposure to pollen can contribute to increased hospital admissions for asthma
      exacerbation. This study applied an ecological time series analysis to examine
      associations between atmospheric concentrations of different pollen types and the
      risk of hospitalization for asthma in London from 2005 to 2011. The analysis
      examined short-term associations between daily pollen counts and hospital
      admissions in the presence of seasonal and long-term patterns, and allowed for
      time lags between exposure and admission. Models were adjusted for temperature,
      precipitation, humidity, day of week, and air pollutants. Analyses revealed an
      association between daily counts (continuous) of grass pollen and adult hospital
      admissions for asthma in London, with a 4-5-day lag. When grass pollen
      concentrations were categorized into Met Office pollen 'alert' levels, 'very
      high' days (vs. 'low') were associated with increased admissions 2-5 days later,
      peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days.
      Increased admissions were also associated with 'high' versus 'low' pollen days at
      a 3-day lag. Results from tree pollen models were inconclusive and likely to have
      been affected by the shorter pollen seasons and consequent limited number of
      observation days with higher tree pollen concentrations. Future reductions in
      asthma hospitalizations may be achieved by better understanding of environmental
      risks, informing improved alert systems and supporting patients to take
      preventive measures.

PMID- 28500393
TI  - Association of serum microRNAs with islet autoimmunity, disease progression and
      metabolic impairment in relatives at risk of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: MicroRNAs (miRNAs) are key regulators of gene expression and
      novel biomarkers for many diseases. We investigated the hypothesis that serum
      levels of some miRNAs would be associated with islet autoimmunity and/or
      progression to type 1 diabetes. METHODS: We measured levels of 93 miRNAs most
      commonly detected in serum. This retrospective cohort study included 150
      autoantibody-positive and 150 autoantibody-negative family-matched siblings
      enrolled in the TrialNet Pathway to Prevention Study. This was a young cohort
      (mean age = 11 years), and most autoantibody-positive relatives were at high risk
      because they had multiple autoantibodies, with 39/150 (26%, progressors)
      developing type 1 diabetes within an average 8.7 months of follow-up. We analysed
      miRNA levels in relation to autoantibody status, future development of diabetes
      and OGTT C-peptide and glucose indices of disease progression. RESULTS: Fifteen
      miRNAs were differentially expressed when comparing autoantibody
      positive/negative siblings (range -2.5 to 1.3-fold). But receiver operating
      characteristic (ROC) analysis indicated low specificity and sensitivity. Seven
      additional miRNAs were differentially expressed among autoantibody-positive
      relatives according to disease progression; ROC returned significant AUC values
      and identified miRNA cut-off levels associated with an increased risk of disease
      in both cross-sectional and survival analyses. Levels of several miRNAs showed
      significant correlations (r values range 0.22-0.55) with OGTT outcomes. miR-21
      3p, miR-29a-3p and miR-424-5p had the most robust associations.
      CONCLUSIONS/INTERPRETATION: Serum levels of selected miRNAs are associated with
      disease progression and confer additional risk of the development of type 1
      diabetes in young autoantibody-positive relatives. Further studies, including
      longitudinal assessments, are warranted to further define miRNA biomarkers for
      prediction of disease risk and progression.

PMID- 28500394
TI  - Bed rest and resistive vibration exercise unveil novel links between skeletal
      muscle mitochondrial function and insulin resistance.
AB  - AIMS/HYPOTHESIS: Physical inactivity has broad implications for human disease
      including insulin resistance, sarcopenia and obesity. The present study tested
      the hypothesis that (1) impaired mitochondrial respiration is linked with blunted
      insulin sensitivity and loss of muscle mass in healthy young men, and (2)
      resistive vibration exercise (RVE) would mitigate the negative metabolic effects
      of bed rest. METHODS: Participants (n = 9) were maintained in energy balance
      during 21 days of bed rest with RVE and without (CON) in a crossover study.
      Mitochondrial respiration was determined by high-resolution respirometry in
      permeabilised fibre bundles from biopsies of the vastus lateralis. A
      hyperinsulinaemic-euglycaemic clamp was used to determine insulin sensitivity,
      and body composition was assessed by dual-energy x-ray absorptiometry (DEXA).
      RESULTS: Body mass (-3.2 +/- 0.5 kg vs -2.8 +/- 0.4 kg for CON and RVE,
      respectively, p < 0.05), fat-free mass (-2.9 +/- 0.5 kg vs -2.7 +/- 0.5 kg, p <
      0.05) and peak oxygen consumption ([Formula: see text]) (10-15%, p < 0.05) were
      all reduced following bed rest. Bed rest decreased insulin sensitivity in the CON
      group (0.04 +/- 0.002 mg kgFFM-1 [pmol l-1] min-1 vs 0.03 +/- 0.002 mg kgFFM-1
      [pmol l-1] min-1 for baseline vs post-CON), while RVE mitigated this response
      (0.04 +/- 0.003 mg kgFFM-1 [pmol l-1] min-1). Mitochondrial respiration
      (oxidative phosphorylation and electron transport system capacity) decreased in
      the CON group but not in the RVE group when expressed relative to tissue weight
      but not when normalised for citrate synthase activity. LEAK respiration,
      indicating a decrease in mitochondrial uncoupling, was the only component to
      remain significantly lower in the CON group after normalisation for citrate
      synthase. This was accompanied by a significant decrease in adenine nucleotide
      translocase protein content. CONCLUSIONS/INTERPRETATION: Reductions in muscle
      mitochondrial respiration occur concomitantly with insulin resistance and loss of
      muscle mass during bed rest and may play a role in the adaptations to physical
      inactivity. Significantly, we show that RVE is an effective strategy to partially
      prevent some of the deleterious metabolic effects of bed rest.

PMID- 28500395
TI  - The human serum protein C4b-binding protein inhibits pancreatic IAPP-induced
      inflammasome activation.
AB  - AIMS/HYPOTHESIS: Inflammasome activation and subsequent IL-1beta production is a
      driver of islet pathology in type 2 diabetes. Oligomers, but not mature amyloid
      fibrils, of human islet amyloid polypeptide (IAPP), which is co-secreted with
      insulin, trigger NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome
      activation. C4b-binding protein (C4BP), present in serum, binds to IAPP and
      affects transition of IAPP monomers and oligomers to amyloid fibrils. We
      therefore hypothesised that C4BP inhibits IAPP-mediated inflammasome activation
      and IL-1beta production. METHODS: Macrophages were exposed to IAPP in the
      presence or absence of plasma-purified human C4BP, and inflammasome activation
      was assessed by IL-1beta secretion as detected by ELISA and reporter cell lines.
      IAPP fibrillation was assessed by thioflavin T assay. Uptake of IAPP-C4BP
      complexes and their effects on phagolysosomal stability were assessed by flow
      cytometry and confocal microscopy. The effect of C4BP regulation of IAPP-mediated
      inflammasome activation on beta cell function was assessed using a clonal rat
      beta cell line. Immunohistochemistry was used to examine the association of IAPP
      amyloid deposits and macrophage infiltration in isolated human and mouse
      pancreatic islets, and expression of C4BP from isolated human pancreatic islets
      was assessed by quantitative PCR, immunohistochemistry and western blot. RESULTS:
      C4BP significantly inhibited IAPP-mediated IL-1beta secretion from primed
      macrophages at physiological concentrations in a dose-dependent manner. C4BP
      bound to and was internalised together with IAPP. C4BP did not affect IAPP uptake
      into phagolysosomal compartments, although it did inhibit its formation into
      amyloid fibrils. The loss of macrophage phagolysosomal integrity induced by IAPP
      incubation was inhibited by co-incubation with C4BP. Supernatant fractions from
      macrophages activated with IAPP inhibited both insulin secretion and viability of
      clonal beta cells in an IL-1beta-dependent manner but the presence of C4BP during
      macrophage IAPP incubation rescued beta cell function and viability. In human and
      mouse islets, the presence of amyloid deposits correlated with higher numbers of
      infiltrating macrophages. Isolated human islets expressed and secreted C4BP,
      which increased with addition of IL-1beta. CONCLUSIONS/INTERPRETATION: IAPP
      deposition is associated with inflammatory cell infiltrates in pancreatic islets.
      C4BP blocks IAPP-induced inflammasome activation by preventing the loss of
      macrophage phagolysosomal integrity required for NLRP3 activation. The
      consequence of this is the preservation of beta cell function and viability. C4BP
      is secreted directly from human pancreatic islets and this increases in response
      to inflammatory cytokines. We therefore propose that C4BP acts as an
      extracellular chaperone protein that limits the proinflammatory effects of IAPP.

PMID- 28500396
TI  - SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event
      Reporting System.
AB  - AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are
      indicated for the treatment of type 2 diabetes and may also improve glucose
      control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may
      favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports
      in which an SGLT2i was listed among suspect or concomitant drugs in the US Food
      and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first
      analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to
      extract the number of reports, background indications and concomitant
      medications, and to calculate proportional reporting ratios (PRRs) and safety
      signals. We then mined single FAERS files from the first quarter (Q1) of 2014 to
      2016 Q3 to obtain detailed information on DKA reports. RESULTS: The FAERS
      database contains >2500 DKA reports in which SGLT2i are listed as suspect or
      concomitant drugs. The PRR of DKA in reports including vs those not including an
      SGLT2i and having a diabetes indication was 7.9 (95% CI 7.5, 8.4) and was higher
      for type 1 diabetes. Several concomitant conditions were less prevalent in DKA
      reports with SGLT2i vs DKA reports filed for other drugs. A detailed analysis of
      2397 DKA reports for SGLT2i from 2014 Q1 to 2016 Q3 revealed a predominance of
      women, an extremely wide range of age and body weight, and a highly variable
      duration of SGLT2i treatment before onset of DKA. In 37 individuals (1.54%), DKA
      was fatal. CONCLUSIONS/INTERPRETATION: Based on the profile of these reports,
      SGLT2i-associated DKA may not be limited to any particular demographic or
      comorbid subpopulation and can occur at any duration of SGLT2i use. DATA
      AVAILABILITY: A list of FDA reports analysed in the study is available in the
      figshare repository, 10.6084/m9.figshare.4903211 . Other data are available from
      the corresponding author on reasonable request.

PMID- 28500397
TI  - Analysis of lethal and sublethal impacts of environmental disasters on sperm
      whales using stochastic modeling.
AB  - Mathematical models are essential for combining data from multiple sources to
      quantify population endpoints. This is especially true for species, such as
      marine mammals, for which data on vital rates are difficult to obtain. Since the
      effects of an environmental disaster are not fixed, we develop time-varying
      (nonautonomous) matrix population models that account for the eventual recovery
      of the environment to the pre-disaster state. We use these models to investigate
      how lethal and sublethal impacts (in the form of reductions in the survival and
      fecundity, respectively) affect the population's recovery process. We explore two
      scenarios of the environmental recovery process and include the effect of
      demographic stochasticity. Our results provide insights into the relationship
      between the magnitude of the disaster, the duration of the disaster, and the
      probability that the population recovers to pre-disaster levels or a biologically
      relevant threshold level. To illustrate this modeling methodology, we provide an
      application to a sperm whale population. This application was motivated by the
      2010 Deepwater Horizon oil rig explosion in the Gulf of Mexico that has impacted
      a wide variety of species populations including oysters, fish, corals, and
      whales.

PMID- 28500399
TI  - Childhood and teenage physical activity and breast cancer risk.
AB  - PURPOSE: Adult physical activity is associated with reduced breast cancer risk,
      but few studies have evaluated activity before adulthood. Early life may be an
      important period because of rapid breast development and hormonal changes. This
      study contributes new information by examining childhood (ages 5-12) and teenage
      (ages 13-19) activity separately and overall. METHODS: The Sister Study is a
      cohort of 50,884 women aged 35-74. Women reported age 5-19 sports/exercise
      activities and age 10 and 16 unstructured activities. Both hours and MET-hours of
      activity were considered in association with breast cancer overall, by ER status,
      and by menopausal status. Hazard ratios (HRs) and 95% confidence intervals (CIs)
      were calculated with Cox proportional hazards models. RESULTS: 2416 cases were
      diagnosed during follow-up (mean = 6.4 years). Participation in 7+ hours (vs <1
      h) per week of sports/exercise during ages 5-19 was associated with reduced
      breast cancer risk (HR = 0.75; 95% CI 0.57-0.99). 7+ hours (vs <1 h) per week of
      unstructured physical activity at age 16, but not age 10, was inversely
      associated with breast cancer (HR = 0.81; 95% CI 0.70-0.95). Associations were
      more pronounced for ER+ tumors, especially for activity during the childhood
      (ages 5-12) period. Due to low correlation between childhood/teenage and
      adulthood activity in this study (r = 0.1), it is unlikely that recent activity
      explains our results. CONCLUSIONS: Findings from this large cohort indicate
      higher levels of physical activity during ages 5-19 are inversely associated with
      breast cancer risk, supporting early life as a window of susceptibility for
      breast cancer development.

PMID- 28500398
TI  - Comparative clinical utility of tumor genomic testing and cell-free DNA in
      metastatic breast cancer.
AB  - PURPOSE: Breast cancer metastases differ biologically from primary disease;
      therefore, metastatic biopsies may assist in treatment decision making.
      Commercial genomic testing of both tumor and circulating tumor DNA have become
      available clinically, but utility of these tests in breast cancer management
      remains unclear. METHODS: Patients undergoing a clinically indicated metastatic
      tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood
      were collected at the time of disease progression before subsequent therapy, and
      patients were followed for response on subsequent treatment. Tumor testing (n =
      53) and concurrent cell-free DNA (n = 32) in a subset of patients was performed
      using CLIA-approved assays. RESULTS: The proportion of patients with a genomic
      alteration was lower in tumor than in blood (69 vs. 91%; p = 0.06). After
      restricting analysis to alterations covered on both platforms, 83% of tumor
      alterations were detected in blood, while 90% of blood alterations were detected
      in tumor. Mutational load specific for the panel genes was calculated for both
      tumor and blood. Time to progression on subsequent treatment was significantly
      shorter for patients whose tumors had high panel-specific mutational load (HR
      0.31, 95% CI 0.12-0.78) or a TP53 mutation (HR 0.35, 95% CI 0.20-0.79), after
      adjusting for stage at presentation, hormone receptor status, prior treatment
      type, and number of lines of metastatic treatment. CONCLUSIONS: Treating
      oncologists must distinguish platform differences from true biological
      heterogeneity when comparing tumor and cfDNA genomic testing results. Tumor and
      concurrent cfDNA contribute unique genomic information in metastatic breast
      cancer patients, providing potentially useful biomarkers for aggressive
      metastatic disease.

PMID- 28500400
TI  - Bioflocculation potentials of a uronic acid-containing glycoprotein produced by
      Bacillus sp. AEMREG4 isolated from Tyhume River, South Africa.
AB  - Bioflocculants are secondary metabolites produced by microorganisms during their
      growth which have received attentions due to their biodegradability,
      innocuousness and lack of secondary pollution from degradation intermediates.
      This study reports on a bioflocculant produced by Bacillus specie isolated from
      Thyume River in South Africa. The bacterial isolate was identified through 16S
      rDNA sequencing and the BLAST analysis of the nucleotide sequences revealed 99%
      similarity to Bacillus sp. BCT-7112. The sequence was subsequently deposited in
      the GenBank as Bacillus sp. AEMREG4 with accession number KP406729. The optimum
      culture conditions for bioflocculant production were an inoculum size 4% (v/v)
      (80%) and starch (81%) as well as yeast extract (82%) as sole carbon and nitrogen
      sources, respectively. Addition of Ca2+ greatly enhanced the flocculating
      activity (76%) of crude bioflocculant over a wide range of pH 4-10 and retained
      high flocculating activity when heated at 100  degrees C for 1 h. Chemical
      analyses of the purified bioflocculant revealed carbohydrate (79% w/w) as a
      predominant component followed by uronic acid (15% w/w) and protein (5% w/w).
      Fourier transform infrared spectrum revealed the presence of carboxyl, hydroxyl
      and methoxyl groups as the functional groups responsible for flocculation and the
      high flocculation activity achieved portends its industrial applicability.

PMID- 28500401
TI  - Sources of beta-galactosidase and its applications in food industry.
AB  - The enzyme beta-galactosidases have been isolated from various sources such as
      bacteria, fungi, yeast, vegetables, and recombinant sources. This enzyme holds
      importance due to its wide applications in food industries to manufacture lactose
      hydrolyzed products for lactose-intolerant people and the formation of
      glycosylated products. Absorption of undigested lactose in small intestine
      requires the activity of this enzyme; hence, the deficiency of this enzyme leads
      to lactose intolerance. Lactose intolerance affects around 70% of world's adult
      population, while the prevalence rate of lactose intolerance is 60% in Pakistan.
      beta-Galactosidases are not only used to manufacture lactose-free products but
      also employed to treat whey, and used in prebiotics. This review focuses on
      various sources of beta-galactosidase and highlights the importance of beta
      galactosidases in food industries.

PMID- 28500402
TI  - Identification and characterization of a grain micronutrient-related OsFRO2 rice
      gene ortholog from micronutrient-rich little millet (Panicum sumatrense).
AB  - Minor millets are considered as nutrient-rich cereals having significant effect
      in improving human health. In this study, a rice ortholog of Ferric Chelate
      Reductase (FRO2) gene involved in plant metal uptake has been identified in iron
      rich Little millet (LM) using PCR and next generation sequencing-based strategy.
      FRO2 gene-specific primers designed from rice genome amplified 2.7 Kb fragment in
      LM genotype RLM-37. Computational genomics analyses of the sequenced amplicon
      showed high level sequence similarity with rice OsFRO2 gene. The predicted gene
      structure showed the presence of 6 exons and 5 introns and its protein sequence
      was found to contain ferric reductase and NOX_Duox_Like_FAD_NADP domains.
      Further, 3D structure analysis of FCR-LM model protein (494 amino acids) shows
      that it has 18 helices, 10 beta sheets, 10 strands, 41 beta turn and 5 gamma turn
      with slight deviation from the FCR-Os structure. Besides, the structures of FCR
      LM and FCR-Os were modelled followed by molecular dynamics simulations. The
      overall study revealed both sequence and structural similarity between the
      identified gene and OsFRO2. Thus, a putative ferric chelate reductase gene has
      been identified in LM paving the way for using this approach for identification
      of orthologs of other metal genes from millets. This also facilitates mining of
      effective alleles of known genes for improvement of staple crops like rice.

PMID- 28500403
TI  - Nanochitosan supports growth of Zea mays and also maintains soil health following
      growth.
AB  - The present study evaluated the effect of nanochitosan in combination with plant
      growth promoting rhizobacteria (PGPR), PS2 and PS10 on maize growth. The PGPR
      were earlier recognized as Bacillus spp. on the basis of 16S rDNA sequencing. The
      observation revealed enhanced plant health parameters like seed germination (from
      60 to 96.97%), plant height (1.5-fold increase), and leaf area (twofold).
      Variability in different physicochemical parameters (pH, oxidizable organic
      carbon, available phosphorous, available potassium, ammoniacal nitrogen and
      nitrate nitrogen) was observed. Activities of soil health indicator enzymes
      (dehydrogenase, fluorescein diacetate hydrolysis and alkaline phosphatase) were
      also enhanced 2 to 3 fold. Plant metabolites with respect to different treatments
      were also analyzed using gas chromatography-mass spectroscopy (GC-MS) and the
      result revealed an increase in the amounts of alcohols, acid ester and aldehyde
      compounds. Increase in organic acids indicates increased stress tolerance
      mechanism operating in maize plant after treatment of nanochitosan.

PMID- 28500404
TI  - Analysis of genetic structure and interrelationships in lentil species using
      morphological and SSR markers.
AB  - Genetic structure and relationships of 130 lentil accessions belonging to six
      taxa were analysed. For this purpose, seven morphological traits and 31
      polymorphic simple sequence repeat (SSR) primers were used for this purpose.
      Morphological traits grouped lentil accessions into five main clusters. SSR
      primers collectively amplified 139 polymorphic alleles in a range of 2-10 with an
      average of 4.48 alleles. The size of amplified alleles varied from 50 to 650 bp.
      Polymorphism information content (PIC) ranged from 0.02 to 0.85 with an average
      of 0.46. Neighbour-joining tree grouped accessions broadly according to their
      taxonomic ranks, except L. culinaris ssp. odemensis. Analysis of molecular
      variance (AMOVA) revealed that a major portion (82.0%) of genetic variance
      resided within species, while only 18% resided among species. Bayesian model
      based STRUCTURE analysis assigned all accessions into five clusters and showed
      some admixture within individuals. Cluster analysis showed that cultivated Lens
      accessions of Ethiopian origin clustered separately, from other cultivated
      accessions indicating its distinct lineage. Among the analysed lentil species, L.
      culinaris ssp. odemensis seemed to have conserved genetic background and needs
      revision of its taxonomic status. Results of present study provide important
      information on genetic diversity and relationships among different wild and
      cultivated taxa of lentil. Thus, these results can be useful in designing
      breeding strategies for future improvement and taxonomic implications in lentil.

PMID- 28500405
TI  - EST-SSR marker revealed effective over biochemical and morphological scepticism
      towards identification of specific turmeric (Curcuma longa L.) cultivars.
AB  - Turmeric (Curcuma longa L., family Zingiberaceae) is one of the most economically
      important plants for its use in food, medicine, and cosmetic industries. Cultivar
      identification is a major constraint in turmeric, owing to high degree of
      morphological similarity that in turn, affects its commercialization. The present
      study addresses this constraint, using EST-SSR marker based, molecular
      identification of 8 elite cultivars and 88 accessions in turmeric. Fifty EST-SSR
      primers were screened against eight cultivars of turmeric (Suroma, Roma,
      Lakadong, Megha, Alleppey Supreme, Kedaram, Pratibha, and Suvarna); out of which
      11 primers showed polymorphic banding pattern. The polymorphic information
      content (PIC) of these primers ranged from 0.13 to 0.48. However, only three SSR
      loci (CSSR 14, CSSR 15, and CSSR 18) gave reproducible unique banding pattern
      clearly distinguishing the cultivars 'Lakadong' and 'Suvarna' from other
      cultivars tested. These three unique SSR markers also proved to be effective in
      identification of 'Lakadong' cultivars when analysed with 88 accessions of
      turmeric collected from different agro-climatic regions. Furthermore, two
      identified cultivars (Lakadong and Suvarna) could also be precisely
      differentiated when analysed and based on phylogenetic tree, with other 94
      genotypes of turmeric. The novel SSR markers can be used for identification and
      authentication of two commercially important turmeric cultivars 'Lakadong' and
      'Suvarna'.

PMID- 28500406
TI  - Assessment of genetic diversity of sesame accessions collected from different
      ecological regions using sequence-related amplified polymorphism markers.
AB  - Sequence-related amplified polymorphism (SRAP) markers were used to assess the
      genetic diversity among a collection of 52 sesame accessions representing
      different geographical environments, including eight Saudi landraces. A
      combination of seventeen primers generated a high number of alleles (365) with
      100% polymorphism. The polymorphic information content (PIC) and primer
      discrimination power (DP) recorded overall means of 0.88 and 5.88, respectively.
      Genetic similarity values based on Jaccard coefficients ranged from 0.12 to 0.49,
      with an average similarity value of 0.30, indicating both high genetic distance
      and a wide genetic basis of the investigated accessions. The unweighted pair
      group method with arithmetic mean (UPGMA) dendrogram grouped 48 of 52 accessions
      into seven main clusters, and five accessions failed to form clusters and were
      separated individually. However, subclusters separated the accessions and,
      considering the relatedness of accessions and their geographical origin, formed
      distinct diversity among groups. Saudi landraces showed the widest genetic basis
      compared with other introduced accessions that were distributed throughout the
      dendrogram, indicating that agro-ecological zones were indistinguishable by
      cluster analysis. SRAP analysis revealed a high degree of genetic polymorphism in
      sesame accessions investigated and showed weak association between geographical
      origin and SRAP patterns. This wide genetic variability should be considered for
      sesame breeding programs.

PMID- 28500407
TI  - Phytochemical profile and free radical nitric oxide (NO) scavenging activity of
      Averrhoa bilimbi L. fruit extract.
AB  - Averrhoa bilimbi L. belongs to family Oxalidaceae. Traditionally, people use this
      plant (root, bark, leaves and fruits) for treating several illnesses include
      itches, boils, syphilis, whooping cough, hypertension, fever and inflammation.
      The aim of the study was to evaluate the nitric oxide (NO) scavenging activity
      and GC-MS analysis of A. bilimbi L. fruit extract. Averrhoa bilimbi L. fruits
      were collected for the preliminary phytochemical analysis, antioxidant scavenging
      activity and biologically important compounds were identified by GC-MS analysis.
      The preliminary phytochemicals, GC-MS, total phenolic content and NO scavenging
      activity of the plant were analysed. In the present investigation, the A. bilimbi
      L. fruit extract has major phytochemicals. Among the 151 compounds identified in
      GC-MS, 15 compounds are found to have diverse biological activity. We also
      observed that the A. bilimbi L. fruit extract has high level of total phenolic
      compounds at a concentration of 209.25 GAE mg/g. Presence of phenolic compound
      apparently explains the antioxidant activity of the plant. Antioxidant activity
      of A. bilimbi L. fruit extract is proven from its high level of NO scavenging
      activity of potent IC50 value of 108.10. From the above study, it is apparent
      that the A. bilimbi L. fruit extract is a rich source of phytochemicals (natural
      products) with biological activity. The GC-MS report on this fruit proves that
      natural products have pharmacologically and biologically active compounds. A high
      phenolic content is observed in our study. A. bilimbi L. fruit extract is also
      found to have NO scavenging activity in our study.

PMID- 28500408
TI  - Scheduling internal medicine resident rotations to ensure fairness and facilitate
      continuity of care.
AB  - Completing a residency program is a requirement for medical students before they
      can practice medicine independently. Residency programs in internal medicine must
      undergo a series of supervised rotations in elective, inpatient, and ambulatory
      units. Typically, a team of chief residents is charged to develop a yearly
      rotational schedule. This process is complex, as it needs to consider academic,
      managerial, regulatory, and legal restrictions while also facilitating the
      provision of patient care, ensuring a diverse educational experience, balancing
      the workload, and improving resident satisfaction. This study proposes (1) a
      multi-stage multi-objective optimization approach for generating yearlong weekly
      resident rotation schedules and (2) the use of Analytical Hierarchy Process (AHP)
      to compare schedules across multiple criteria to select those that are more
      equitable and hence to facilitate their adoption and implementation. Furthermore,
      the proposed approach allows the scheduling of periodic clinic rotation schemes
      that are commonly used to facilitate continuity of care, such as "4+1" or the
      "8+2" policies. In the "4+1" policy residents rotate for four consecutive weeks
      in different units prior to return for a week to a predetermined clinical post.
      Similarly, in the "8+2" policy, residents rotate eight weeks across multiple
      units before doing a two week rotation at a predetermined clinic.

PMID- 28500410
TI  - Erratum to: Aldo-ketoreductase 1 (AKR1) improves seed longevity in tobacco and
      rice by detoxifying reactive cytotoxic compounds generated during ageing.

PMID- 28500409
TI  - Physicochemical and biological characteristics of BMP-2/IGF-1-loaded three
      dimensional coaxial electrospun fibrous membranes for bone defect repair.
AB  - Coaxial electrospun fibrous membranes show favorable mechanical properties for
      use in guided bone regeneration (GBR). We used coaxial electrospinning technology
      to fabricate three-dimensional nanofiber membranes loaded with BMP-2 and IGF-1,
      and assessed the physicochemical and biological properties of these novel
      membranes in vitro. We fabricated four experimental groups of BMP-2/IGF-1/BSA
      loaded membranes with different flow ratios (shell/core). Membrane
      characteristics were assessed by scanning and transmission electron microscopy,
      and laser confocal microscopy. Physicochemical and drug release properties were
      evaluated based on contact angle, mechanical property testing, X-ray diffraction
      analysis, and ELISA. The membranes were seeded with bone marrow-derived
      mesenchymal stem cells (BMMSCs) to estimate their biological properties based on
      cell viability and alkaline phosphatase (ALP) activity. The four membrane groups
      presented uniform diameters and core-shell structures. Acceleration of the shell
      solution flow rate increased the contact angle and mechanical properties of the
      fibrous membrane, while dual-factor addition did not impact fiber structure. Each
      drug-loaded membrane showed a gradually increasing release curve, with varying
      degrees of burst and sustained release. Compared to the other groups, the
      membranes with a core-shell flow ratio of 1:10 showed better drug-loading
      capacity and sustained release performance, higher biological properties and good
      barrier function. Optimal parameters were chosen based on the physical and
      chemical characteristics and biological properties of the membrane. Our results
      imply that the BMP-2/IGF-1/BSA-loaded coaxial electrospun fibrous membrane with
      optimum parameters is a suitable barrier membrane for GBR, and releases multiple
      factors promoting osteoconduction and osteoinduction.

PMID- 28500411
TI  - A hairy-leaf gene, BLANKET LEAF, of wild Oryza nivara increases photosynthetic
      water use efficiency in rice.
AB  - BACKGROUND: High water use efficiency is essential to water-saving cropping.
      Morphological traits that affect photosynthetic water use efficiency are not well
      known. We examined whether leaf hairiness improves photosynthetic water use
      efficiency in rice. RESULTS: A chromosome segment introgression line (IL-hairy)
      of wild Oryza nivara (Acc. IRGC105715) with the genetic background of Oryza
      sativa cultivar 'IR24' had high leaf pubescence (hair). The leaf hairs developed
      along small vascular bundles. Linkage analysis in BC5F2 and F3 populations showed
      that the trait was governed by a single gene, designated BLANKET LEAF (BKL), on
      chromosome 6. IL-hairy plants had a warmer leaf surface in sunlight, probably due
      to increased boundary layer resistance. They had a lower transpiration rate under
      moderate and high light intensities, resulting in higher photosynthetic water use
      efficiency. CONCLUSION: Introgression of BKL on chromosome 6 from O. nivara
      improved photosynthetic water use efficiency in the genetic background of IR24.

PMID- 28500412
TI  - [Hereditary breast and ovarian cancer].
AB  - Hereditary breast and ovarian carcinomas are frequently caused by germline
      mutations of the BRCA1 and BRCA2 genes (BRCA1/2 syndromes) and are often less
      associated with other hereditary syndromes such as Li-Fraumeni and Peutz-Jeghers.
      The BRCA1/2 proteins have a special role in DNA repair. Therefore, loss of
      function due to mutation causes an accumulation of mutations in other genes and
      subsequent tumorigenesis at an early age. BRCA1/2 mutations are irregularly
      distributed over the length of the genes without hot spots, although special
      mutations are known. Breast and ovarian cancer occur far more frequently in women
      with BRCA1/2 germline mutations compared with the general population. Breast
      cancer occurs increasingly from the age of 30, ovarian cancer in BRCA1 syndrome
      from the age of 40 and BRCA2 from the age of 50. Suspicion of a BRCA syndrome
      should be prompted in the case of clustering of breast cancer in 1st degree
      relatives, in particular at a young age, if breast and ovarian cancer have
      occurred, and if cases of male breast cancer are known. Breast carcinomas with
      medullary differentiation seem to predominate in BRCA syndromes, but other
      carcinoma types may also occur. BRCA germline mutations seem to occur frequently
      in triple-negative breast carcinomas, whereas an association with ductal
      carcinoma in situ (DCIS) is rare. Ovarian carcinomas in BRCA syndromes are
      usually high-grade serous, mucinous carcinomas and borderline tumors are unusual.
      Pathology plays a special role within the multidisciplinary team in the
      recognition of patients with hereditary cancer syndromes.

PMID- 28500414
TI  - Comparative Metabolomic Analysis of the Green Microalga Chlorella sorokiniana
      Cultivated in the Single Culture and a Consortium with Bacteria for Wastewater
      Remediation.
AB  - Co-culture of microalgae with many types of bacteria usually comes out with
      significant different treatment efficiencies for COD, nitrogen, and phosphorus in
      wastewater remediation, compared with the single culture. In order to understand
      the mechanism behind, a comparative experiment was designed in this study, using
      the green microalgae species Chlorella sorokiniana in the single culture and a
      consortium with a bacterium, Pseudomonas H4, for nutrient removal. Comparative
      metabolome profile analysis was conducted to reveal the Chlorella cell responses
      to the synergistic growth with the bacteria, and possible relations between the
      metabolic regulation of microalgae and the nutrient degradation were discussed.
      The detectable differential metabolites of Chlorella belonged to several classes,
      including carbohydrates, fatty acids, amino acids, phosphates, polyols, etc. The
      orthogonal partial least squares discriminant analysis (OPLS-DA) model of the
      identified metabolites suggests the metabolism in this alga was significantly
      affected by the bacteria, corresponding to different treatment behaviors.

PMID- 28500413
TI  - Impaired Pulmonary Function is an Additional Potential Mechanism for the
      Reduction of Functional Capacity in Clinically Stable Fontan Patients.
AB  - Central factors negatively affect the functional capacity of Fontan patients
      (FP), but "non-cardiac" factors, such as pulmonary function, may contribute to
      their exercise intolerance. We studied the pulmonary function in asymptomatic FP
      and its correlations with their functional capacity. Pulmonary function and
      cardiopulmonary exercise tests were performed in a prospective study of 27 FP and
      27 healthy controls (HC). Cardiovascular magnetic resonance was used to evaluate
      the Fontan circulation. The mean age at tests, the mean age at surgery, and the
      median follow-up time of FP were 20(+/-6), 8(+/-3), and 11(8-17) years,
      respectively. Dominant ventricle ejection fraction was within normal range. The
      mean of peak VO2 expressed in absolute values (L/min), the relative values to
      body weight (mL/kg/min), and their predicted values were lower in FP compared
      with HC: 1.69 (+/-0.56) vs 2.81 (+/-0.77) L/min; 29.9 (+/-6.1) vs 41.5 (+/-9.3)
      mL/kg/min p < 0.001 and predicted VO2 Peak [71% (+/-14) vs 100% (+/-20) p <
      0.001]. The absolute and predicted values of the forced vital capacity (FVC),
      forced expiratory volume in one second (FEV1), inspiratory capacity (IC), total
      lung capacity (TLC), diffusion capacity of carbon monoxide of the lung (DLCO),
      maximum inspiratory pressure (MIP), and sniff nasal inspiratory pressure (SNIP)
      were also significantly lower in the Fontan population compared to HC. An
      increased risk of restrictive ventilatory pattern was found in patients with
      postural deviations (OD:10.0, IC:1.02-97.5, p = 0.042). There was a strong
      correlation between pulmonary function and absolute peak VO2 [FVC (r = 0.86, p <
      0.001); FEV1 (r = 0.83, p < 0.001); IC (r = 0.84, p < 0.001); TLC (r = 0.79, p <
      0.001); and DLCO (r = 0.72, p < 0.001). The strength of the inspiratory muscles
      in absolute and predicted values was also reduced in FP [-79(+/-28) vs -109(+/
      44) cmH2O (p = 0.004) and 67(+/-26) vs 89(+/-36) % (p = 0.016)]. Thus, we
      concluded that the pulmonary function was impaired in clinically stable Fontan
      patients and the static and dynamic lung volumes were significantly reduced
      compared with HC. We also demonstrated a strong correlation between absolute Peak
      VO2 with the FVC, FEV1, TLC, and DLCO measured by complete pulmonary test.

PMID- 28500415
TI  - Mind-muscle connection training principle: influence of muscle strength and
      training experience during a pushing movement.
AB  - PURPOSE: To investigate the effect of different attentional focus conditions on
      muscle activity during the push-up exercise and to assess the possible influence
      of muscle strength and training experience. METHODS: Eighteen resistance-trained
      men performed 1RM bench press testing and were familiarized with the procedure
      during the first session. In the second session, three different conditions were
      randomly performed: regular push-up and push-up focusing on using the pectoralis
      major and triceps brachii muscles, respectively. Surface electromyography (EMG)
      was recorded and analyzed (EMG normalized to max; nEMG) for the triceps brachii
      and pectoralis major muscles. RESULTS: Participants had on average 8 (SD 6) years
      of training experience and 1RM of 1.25 (SD 0.28) kg per kg bodyweight. Focusing
      on using pectoralis major increased activity in this muscle by 9% nEMG (95% CI 5
      13; Cohen's d 0.60) compared with the regular condition. Triceps activity was not
      significantly influenced by triceps focus although borderline significant, with a
      mean difference of 5% nEMG (95% CI 0-10; Cohen's d 0.30). However, years of
      training experience was positively associated with the ability to selectively
      activate the triceps (beta = 0.41, P = 0.04), but not the pectoralis. Bench press
      1RM was not significantly associated with the ability to selectively activate the
      muscles. CONCLUSION: Pectoralis activity can be increased when focusing on using
      this muscle during push-ups, whereas the ability to do this for the triceps is
      dependent on years of training experience. Maximal muscle strength does not
      appear to be a decisive factor for the ability to selectively activate these
      muscles.

PMID- 28500416
TI  - Effects of breaking up prolonged sitting following low and high glycaemic index
      breakfast consumption on glucose and insulin concentrations.
AB  - PURPOSE: Breaking up prolonged sitting can attenuate the postprandial rise in
      glucose and insulin. Whether such effects are dependent of the glycaemic index
      (GI) of the consumed carbohydrate is unknown. This study examined the acute
      effects of breaking up prolonged sitting following a low GI and a high GI
      breakfast on postprandial glucose and insulin concentrations. PROCEDURES:
      Fourteen adult males aged 22.1 +/- 1.2 years completed four, 4 h experimental
      conditions: high GI breakfast followed by uninterrupted sitting (HGI-SIT), low GI
      breakfast followed by uninterrupted sitting (LGI-SIT), high GI breakfast followed
      by 2 min activity breaks every 20 min (HGI-ACT), and low GI breakfast followed by
      2 min activity breaks every 20 min (LGI-ACT). Positive incremental area under the
      curve (iAUC) for glucose and insulin (mean [95% CI]) for each 4 h experimental
      condition was calculated. Statistical analyses were completed using linear mixed
      models. RESULTS: The sitting * breakfast GI interaction was not significant for
      glucose positive iAUC (P = 0.119). Glucose positive iAUC (mmol/L 4 h-1) was
      significantly lower in the activity breaks conditions than the uninterrupted
      sitting conditions (2.07 [2.24, 2.89] vs. 2.56 [1.74, 2.40], respectively, P =
      0.004) and significantly lower in the low GI conditions than the high GI
      conditions (2.13 [1.80, 2.45] vs. 2.51 [2.18, 2.84], respectively, P = 0.022).
      Insulin concentrations did not differ between conditions (P >= 0.203).
      CONCLUSIONS: Breaking up prolonged sitting and lowering breakfast GI
      independently reduced postprandial glucose responses. This indicates that
      interrupting prolonged sitting and reducing dietary GI are beneficial approaches
      for reducing cardiometabolic disease risk.

PMID- 28500418
TI  - Weight Loss After Bariatric Surgery: Do Clinical and Behavioral Factors Explain
      Racial Differences?
AB  - BACKGROUND: Prior studies have suggested less weight loss among African American
      compared to Caucasian patients; however, few studies have been able to
      simultaneously account for baseline differences in other demographic, clinical,
      or behavioral factors. METHODS: We interviewed patients at two weight loss
      surgery (WLS) centers and conducted chart reviews before and after WLS. We
      compared weight loss post-WLS by race/ethnicity and examined baseline
      demographic, clinical (BMI, comorbidities, quality of life), and behavioral
      (eating behavior, physical activity level, alcohol intake) factors that might
      explain observed racial differences in weight loss at 1 and 2 years after WLS.
      RESULTS: Of 537 participants who underwent either Roux-en-Y Gastric Bypass (54%)
      or gastric banding (46%), 85% completed 1-year follow-up and 73% completed 2-year
      follow-up. Patients lost a mean of 33.00% of initial weight at year 1 and 32.43%
      at year 2 after bypass and 16.07% and 17.56 % respectively after banding. After
      adjustment for other demographic characteristics and type of surgery, African
      Americans lost an absolute 5.93 +/- 1.49% less weight than Caucasian patients
      after bypass (p < 0.001) and 4.72 +/- 1.96% less weight after banding. Of the
      other demographic, clinical, behavioral factors considered, having diabetes and
      perceived difficulty making dietary changes at baseline were associated with less
      weight loss among gastric bypass patients whereas having a diagnosis of anxiety
      disorder was associated with less weight loss among gastric banding patients. The
      association between race and weight loss did not substantially attenuate with
      additional adjustment for these clinical and behavioral factors, however.
      CONCLUSION: African American patients lost significantly less weight than
      Caucasian patients. Racial differences could not be explained by baseline
      demographic, clinical, or behavioral characteristics we examined.

PMID- 28500419
TI  - Bariatric Surgery as a Bridge to Renal Transplantation in Patients with End-Stage
      Renal Disease.
AB  - BACKGROUND: Obesity is a relative contraindication to organ transplantation.
      Preliminary reports suggest that bariatric surgery may be used as a bridge to
      transplantation in patients who are not eligible for transplantation because of
      morbid obesity. SETTING: The Bariatric Center at Tampa General Hospital,
      University of South Florida, Tampa, Florida. METHODS: We reviewed the outcomes of
      16 consecutive patients on hemodialysis for end-stage renal disease (ESRD) who
      underwent bariatric surgery from 1998 to 2016. Demographics, comorbidities,
      weight loss, as well as transplant status were reported. Data is mean +/- SD.
      RESULTS: Six men and ten women aged 43-66 years (median = 54 years) underwent
      laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 12), laparoscopic adjustable
      gastric banding (LAGB, n = 3), or laparoscopic sleeve gastrectomy (LSG, n = 1).
      Preoperative BMI was 48 +/- 8 kg/m2. Follow-up to date was 1-10 years (median =
      2.8 years); postoperative BMI was 31 +/- 7 kg/m2; %EBWL was 62 +/- 24. Four
      patients underwent renal transplantation (25%) between 2.5-5 years after
      bariatric surgery. Five patients are currently listed for transplantation. Five
      patients were not listed for transplantation due to persistent comorbidities; two
      of these patients died as a consequence of their comorbidities (12.5%) more than
      1 year after bariatric surgery. Two patients were lost to follow-up (12.5%).
      CONCLUSION: Bariatric surgery is effective in patients with ESRD and improves
      access to renal transplantation. Bariatric surgery offers a safe approach to
      weight loss and improvement in comorbidities in the majority of patients.
      Referrals of transplant candidates with obesity for bariatric surgery should be
      considered early in the course of ESRD.

PMID- 28500417
TI  - Pathophysiology and Treatment of Memory Dysfunction After Traumatic Brain Injury.
AB  - Memory is fundamental to everyday life, and cognitive impairments resulting from
      traumatic brain injury (TBI) have devastating effects on TBI survivors. A
      contributing component to memory impairments caused by TBI is alteration in the
      neural circuits associated with memory function. In this review, we aim to bring
      together experimental findings that characterize behavioral memory deficits and
      the underlying pathophysiology of memory-involved circuits after TBI. While there
      is little doubt that TBI causes memory and cognitive dysfunction, it is difficult
      to conclude which memory phase, i.e., encoding, maintenance, or retrieval, is
      specifically altered by TBI. This is most likely due to variation in behavioral
      protocols and experimental models. Additionally, we review a selection of
      experimental treatments that hold translational potential to mitigate memory
      dysfunction following injury.

PMID- 28500420
TI  - Purification, biochemical, and structural characterization of a novel
      fibrinolytic enzyme from Mucor subtilissimus UCP 1262.
AB  - Fibrinolytic proteases are enzymes that degrade fibrin. They provide a promising
      alternative to existing drugs for thrombolytic therapy. A protease isolated from
      the filamentous fungus Mucor subtilissimus UCP 1262 was purified in three steps
      by ammonium sulfate fractionation, ion exchange, and molecular exclusion
      chromatographies, and characterized biochemically and structurally. The purified
      protease exhibited a molecular mass of 20 kDa, an apparent isoelectric point of
      4.94 and a secondary structure composed mainly of alpha-helices. Selectivity for
      N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as substrate suggests that this enzyme
      is a chymotrypsin-like serine protease, whose activity was enhanced by the
      addition of Cu2+, Mg2+, and Fe2+. The enzyme showed a fibrinolytic activity of
      22.53 U/mL at 40  degrees C and its contact with polyethylene glycol did not lead
      to any significant alteration of its secondary structure. This protein represents
      an important example of a novel fibrinolytic enzyme with potential use in the
      treatment of thromboembolic disorders such as strokes, pulmonary emboli, and deep
      vein thrombosis.

PMID- 28500422
TI  - Are Reptiles Reservoirs of Leptospirosis? A Brief Discussion Based on Serological
      Studies.

PMID- 28500421
TI  - Seasonal Fluctuations of Astrovirus, But Not Coronavirus Shedding in Bats
      Inhabiting Human-Modified Tropical Forests.
AB  - Emerging infectious diseases (EIDs) are considered a major threat to global
      health. Most EIDs appear to result from increased contact between wildlife and
      humans, especially when humans encroach into formerly pristine habitats. Habitat
      deterioration may also negatively affect the physiology and health of wildlife
      species, which may eventually lead to a higher susceptibility to infectious
      agents and/or increased shedding of the pathogens causing EIDs. Bats are known to
      host viruses closely related to important EIDs. Here, we tested in a
      paleotropical forest with ongoing logging and fragmentation, whether habitat
      disturbance influences the occurrence of astro- and coronaviruses in eight bat
      species. In contrast to our hypothesis, anthropogenic habitat disturbance was not
      associated with corona- and astrovirus detection rates in fecal samples. However,
      we found that bats infected with either astro- or coronaviruses were likely to be
      coinfected with the respective other virus. Additionally, we identified two more
      risk factors influencing astrovirus shedding. First, the detection rate of
      astroviruses was higher at the beginning of the rainy compared to the dry season.
      Second, there was a trend that individuals with a poor body condition had a
      higher probability of shedding astroviruses in their feces. The identification of
      risk factors for increased viral shedding that may potentially result in
      increased interspecies transmission is important to prevent viral spillovers from
      bats to other animals, including humans.

PMID- 28500424
TI  - Cardiac surgery-associated acute kidney injury: tools for enriching clinical
      trial populations.

PMID- 28500423
TI  - Physiological Self-Regulation Buffers the Relationship between Impulsivity and
      Externalizing Behaviors among Nonclinical Adolescents.
AB  - Trait impulsivity is a risk factor for rule breaking and aggressive
      (externalizing) behaviors among nonclinical youth. Buffers of trait-based risk
      are of practical interest to preventing externalizing behaviors. One such buffer
      may be the capacity and efforts of a child to self-regulate their physiology.
      Youth who possess baseline physiological self-regulatory capacities are more
      likely to maintain adaptive engagement with their environment and may be less
      prone to impulsively rule break or be aggressive. Similarly, youth who are able
      to use self-regulatory skills to calm their physiology in times of stress may be
      less likely to externalize distress. This study examined self-regulatory capacity
      and efforts as a moderator of the relationship between trait impulsivity and
      externalizing behaviors, cross-sectionally and prospectively. We hypothesized
      that the effect of trait impulsivity on externalizing behaviors would depend on
      the presence of baseline self-regulatory capacity and/or self-regulatory efforts
      during stress. Participants were 134 nonclinical adolescents (Mage = 12.59, SD =
      1.20 51.9% female, 71% Caucasian). Trait impulsivity was measured using a
      parental report questionnaire. Physiological self-regulatory capacity and efforts
      were measured through collection of electrocardiogram data during a resting
      baseline and a stressful, unsolvable anagram task, respectively. Physiological
      self-regulation was quantified by calculating respiratory sinus arrhythmia scores
      across baseline and stress tasks. Respiratory sinus arrhythmia is the change in
      heart rate across the breathing cycle, and is hypothesized to index physiological
      self-regulation capacity and efforts under specific conditions. The results
      indicated that physiological self-regulation capacity, but not efforts, moderated
      the effect of trait impulsivity on externalizing behaviors prospectively.
      Stronger physiological self-regulatory capacity buffered the effect of greater
      trait impulsivity. Implications of these findings among typically developing
      youth are discussed.

PMID- 28500425
TI  - Hepatic glucuronidation of 4-tert-octylphenol in humans: inter-individual
      variability and responsible UDP-glucuronosyltransferase isoforms.
AB  - 4-tert-Octylphenol (4-tOP) is an endocrine-disrupting chemical. It is mainly
      metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in
      humans. The purpose of this study was to assess inter-individual variability in
      and the possible roles of UGT isoforms in hepatic 4-tOP glucuronidation in the
      humans. 4-tOP glucuronidation activities in the liver microsomes and recombinant
      UGTs of humans were assessed at broad substrate concentrations, and kinetics were
      analyzed. Correlation analyses between 4-tOP and diclofenac or 4-hydroxybiphenyl
      activities in pooled and individual human liver microsomes were also performed.
      Typical CLint values were 17.8 mL/min/mg protein for the low type, 25.2 mL/min/mg
      protein for the medium type, and 47.7 mL/min/mg protein for the high type. Among
      the recombinant UGTs (13 isoforms) examined, UGT2B7 and UGT2B15 were the most
      active of catalyzing 4-tOP glucuronidation. Although the K m values of UGT2B7 and
      UGT2B15 were similar (0.36 and 0.42 uM, respectively), the CLint value of UGT2B7
      (6.83 mL/min/mg protein) >UGT2B15 (2.35 mL/min/mg protein). Strong correlations
      were observed between the glucuronidation activities of 4-tOP and diclofenac (a
      probe for UGT2B7) or 4-hydroxybiphenyl (a probe for UGT2B15) with 0.79-0.88 of
      Spearman correlation coefficient (r s) values. These findings demonstrate that 4
      tOP glucuronidation in humans is mainly catalyzed by hepatic UGT2B7 and UGT2B15,
      and suggest that these UGT isoforms play important and characteristic roles in
      the detoxification of 4-tOP.

PMID- 28500426
TI  - Identification and evaluation of potential bio-control fungal endophytes against
      Ustilagonoidea virens on rice plants.
AB  - False smut disease of rice is posing an increasing concern for production, not
      only because of the hiking epidemic occurrence in rice production, but also
      because of the challenging specific pathogenesis of the disease. The aim of this
      work was to evaluate the potential of five fungal endophytes to reduce negative
      effects of rice false smut fungus (Ustilagonoidea virens) on rice plants, in both
      the laboratory and greenhouse. Though all the fungal isolates showed the ability
      to inhibit the growth of U. virens with varying degrees, isolate E337 showed
      significant antagonistic activity against the pathogenic fungi. The isolate E337
      was identified as Antennariella placitae by molecular and morphological data
      analysis including 18S rDNA sequence analysis. This isolate showed a significant
      in vitro inhibition of mycelial growth of U. virens by dual culture method and it
      was subsequently tested for its in vivo biocontrol potential on false smut
      disease on rice plants. Greenhouse experiments confirmed that applications of
      conidia of A. placitae protected rice plants by improving rice yield and by
      decreasing the severity of false smut disease on susceptible rice plants. This is
      the first report where A. placitae has been identified as a biocontrol organism.

PMID- 28500427
TI  - A Japanese infant with systemic juvenile xanthogranuloma mimicking severe
      microangiopathy.

PMID- 28500428
TI  - A novel classification method for aid decision of traditional Chinese patent
      medicines for stroke treatment.
AB  - Traditional Chinese patent medicines are widely used to treat stroke because it
      has good efficacy in the clinical environment. However, because of the lack of
      knowledge on traditional Chinese patent medicines, many Western physicians, who
      are accountable for the majority of clinical prescriptions for such medicine, are
      confused with the use of traditional Chinese patent medicines. Therefore, the aid
      decision method is critical and necessary to help Western physicians rationally
      use traditional Chinese patent medicines. In this paper, Manifold Ranking is
      employed to develop the aid-decision model of traditional Chinese patent
      medicines for stroke treatment. First, 115 stroke patients from three hospitals
      are recruited in the cross-sectional survey. Simultaneously, traditional Chinese
      physicians determine the traditional Chinese patent medicines appropriate for
      each patient. Second, particular indicators are explored to characterize the
      population feature of traditional Chinese patent medicines for stroke treatment.
      Moreover, these particular indicators can be easily obtained byWestern physicians
      and are feasible for widespread clinical application in the future. Third, the
      aid-decision model of traditional Chinese patent medicines for stroke treatment
      is constructed based on Manifold Ranking. Experimental results reveal that
      traditional Chinese patent medicines can be differentiated. Moreover, the
      proposed model can obtain high accuracy of aid decision.

PMID- 28500429
TI  - The antibiotic resistome: gene flow in environments, animals and human beings.
AB  - The antibiotic resistance is natural in bacteria and predates the human use of
      antibiotics. Numerous antibiotic resistance genes (ARGs) have been discovered to
      confer resistance to a wide range of antibiotics. The ARGs in natural
      environments are highly integrated and tightly regulated in specific bacterial
      metabolic networks. However, the antibiotic selection pressure conferred by the
      use of antibiotics in both human medicine and agriculture practice leads to a
      significant increase of antibiotic resistance and a steady accumulation of ARGs
      in bacteria. In this review, we summarized, with an emphasis on an ecological
      point of view, the important research progress regarding the collective ARGs
      (antibiotic resistome) in bacterial communities of natural environments, human
      and animals, i.e., in the one health settings.We propose that the resistance gene
      flow in nature is "from the natural environments" and "to the natural
      environments"; human and animals, as intermediate recipients and disseminators,
      contribute greatly to such a resistance gene "circulation."

PMID- 28500430
TI  - Postnatal feeding with high-fat diet induces obesity and precocious puberty in
      C57BL/6J mouse pups: a novel model of obesity and puberty.
AB  - Childhood obesity and obesity-related metabolic complications are induced by a
      high-fat postnatal diet. The lack of a suitable animal model, however, remains a
      considerable challenge in obesity studies. In the current study, we provided high
      fat diet (HFD) to dams during lactation and to pups after weaning. We also
      developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal
      obesity. Results showed that feeding with HFD induces fat deposition and obesity
      in pups. Furthermore, HFD more potently increased the body weight (BW) of male
      than female pups. HFD-fed female pups were obese, underwent precocious puberty,
      and showed increased kisspeptin expression in the hypothalamus. However, parental
      obesity and precocious puberty exerted no synergistic effects on the HFD-induced
      postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed
      litters with normal BW also exhibited precocious puberty. This finding suggested
      that diet composition but not BW triggers puberty onset. Our model suggests good
      construction validity of obesity and precocious puberty. Furthermore, our model
      can also be used to explore the mutual interactions between diet-induced
      postnatal childhood obesity and puberty.

PMID- 28500432
TI  - Quality and readability of online information resources on insomnia.
AB  - The internet is a major source for health information. An increasing number of
      people, including patients with insomnia, search for remedies online; however,
      little is known about the quality of such information. This study aimed to
      evaluate the quality and readability of insomnia-related online information.
      Google was used as the search engine, and the top websites on insomnia that met
      the inclusion criteria were evaluated for quality and readability. The analyzed
      websites belonged to nonprofit, commercial, or academic organizations and
      institutions such as hospitals and universities. Insomnia-related websites
      typically included definitions (85%), causes and risk factors (100%), symptoms
      (95%), and treatment options (90%). Cognitive behavioral therapy for insomnia
      (CBT-I) was the most commonly recommended approach for insomnia treatment, and
      sleep drugs are frequently mentioned. The overall quality of the websites on
      insomnia is moderate, but all the content exceeded the recommended reading ease
      levels. Concerns that must be addressed to increase the quality and
      trustworthiness of online health information include sharing metadata, such as
      authorship, time of creation and last update, and conflicts of interest;
      providing evidence for reliability; and increasing the readability for a layman
      audience.

PMID- 28500433
TI  - The effect of orbital radiation therapy on thyroid-associated orbitopathy
      complicated with dysthyroid optic neuropathy.
AB  - Thyroid-associated orbitopathy (TAO) is an inflammatory autoimmune disorder. The
      most serious complication of TAO is dysthyroid optic neuropathy (DON), which can
      lead to permanent vision loss because of volume expansion in the orbital apex.
      Orbital radiation therapy (ORT) is an anti-inflammatory treatment used in the
      treatment of active TAO. Clinical studies support radiotherapy as having a modest
      effect on DON, and early radiotherapy may protect against disease progression to
      DON. Current studies suggest that radiotherapy is generally safe. However, risks
      still exist in some cases. The possible effects of radiotherapy on TAO,
      especially complicated with DON, are reviewed. The effects of radiotherapy on DON
      are not completely known, and evidence from standardized, prospective, and
      multicenter clinical trials is still lacking.

PMID- 28500431
TI  - Molecular aspects of MERS-CoV.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus
      which can cause acute respiratory distress in humans and is associated with a
      relatively high mortality rate. Since it was first identified in a patient who
      died in a Jeddah hospital in 2012, the World Health Organization has been
      notified of 1735 laboratory-confirmed cases from 27 countries, including 628
      deaths. Most cases have occurred in Saudi Arabia. MERS-CoVancestors may be found
      in OldWorld bats of the Vespertilionidae family. After a proposed bat to camel
      switching event, transmission of MERS-CoV to humans is likely to have been the
      result of multiple zoonotic transfers from dromedary camels. Human-to-human
      transmission appears to require close contact with infected persons, with
      outbreaks mainly occurring in hospital environments. Outbreaks have been
      associated with inadequate infection prevention and control implementation,
      resulting in recommendations on basic and more advanced infection prevention and
      control measures by the World Health Organization, and issuing of government
      guidelines based on these recommendations in affected countries including Saudi
      Arabia. Evolutionary changes in the virus, particularly in the viral spike
      protein which mediates virus-host cell contact may potentially increase
      transmission of this virus. Efforts are on-going to identify specific evidence
      based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been
      shown to have in vitro activity against MERS-CoV. Synthetic peptides and
      candidate vaccines based on regions of the spike protein have shown promise in
      rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine
      encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while
      monoclonal antibody, m336 has given promising results in animal models and has
      potential for use in outbreak situations.

PMID- 28500434
TI  - Comparing the Multicomponent Coping Power Program to Individualized Parent-Child
      Treatment for Improving the Parenting Efficacy and Satisfaction of Parents of
      Children with Conduct Problems.
AB  - This study compared the multicomponent Coping Power (group) program to
      individualized parent-child treatment with respect to changing the parenting
      efficacy and satisfaction of parents of children with conduct problems. One
      hundred fourteen parents of 9-12-year-old children with conduct problems were
      randomized to Coping Power or individualized treatment at an urban children's
      mental health clinic. Parents reported their pre- and post-treatment parenting
      efficacy and parenting satisfaction (Parent Sense of Competence Scale). Mixed
      effect models revealed that parenting efficacy and satisfaction significantly
      increased from pre- to post-treatment, and there was no evidence that this effect
      is different between Coping Power and individualized treatment, even after
      controlling for initial severity of child symptomatology. Findings support the
      effectiveness of Coping Power as an intervention for parenting efficacy and
      satisfaction among parents of children aged 9-12 years with conduct problems.

PMID- 28500435
TI  - Examining the Mechanisms of Therapeutic Change in a Cognitive-Behavioral
      Intervention for Anxious Children: The Role of Interpretation Bias, Perceived
      Control, and Coping Strategies.
AB  - This study examined the role of theoretically meaningful mediators of therapeutic
      change-interpretation bias, perceived control, and coping strategies-in a
      cognitive-behavioral intervention for anxious youth. This is one of the few
      studies that examined the change in potential mediator and outcome variables by
      means of a longitudinal design that included four assessment points:
      pretreatment, in-treatment, post-treatment, and at 4-months follow-up. Forty
      seven 8- to 12-year-old children with a principal DSM-IV diagnosis of anxiety
      disorder participated in the study. On each assessment point, questionnaires
      assessing the mediator variables and a standardized anxiety scale were
      administered to the children. The results showed that perceived control and
      interpretation bias (but not coping strategies) accounted for a significant
      proportion in the variability of various types of anxiety symptoms, providing a
      preliminary support for the notion that these cognitive dimensions' act as
      mechanisms of therapeutic change in cognitive-behavioral therapy for anxious
      children.

PMID- 28500436
TI  - The efficacy of a multimodal analgesia protocol in preventing heterotopic
      ossification after acetabular fractures surgery.
AB  - Background Heterotopic ossification (HO) after joint surgery is always a
      disturbing problem for patients and surgeons. Prophylaxis is the most effective
      therapy. Objective To assess the efficacy and safety of a multimodal analgesia
      protocol that included parecoxib and celecoxib in preventing HO after acetabular
      fracture surgery. Setting Selecting patients from trauma registry of our
      hospital. Method We identified 259 patients who had acetabular fracture surgery
      between January 2008 and December 2014. Hundredsixty-three patients received
      parecoxib and celecoxib (Group A) and 96 patients received no prophylaxis (Group
      B). The presence of HO was assessed according to the classification of Brooker et
      al. at the 12 month postoperative visit. Main outcome measure The differences in
      HO incidence and severity between the two groups. Results 49 patients (30.0%)
      developed HO in the Group A and 44(45.8%) in Group B. The difference in total HO
      incidence between the two groups was significant (P = 0.011 < 0.05, chi2 = 6.530,
      OR 0.508, 95% CI (0.301-0.857). Severe HO (Brooker grade III or IV) developed in
      15 patients (9.2%) in Group A and 17 patients (17.7%) in Group B. Brooker grade I
      + II was 34(20.9%) and 27(28.1%) in each group. The difference in the severity of
      HO between the two Groups was significant (P = 0.008 < 0.05). Conclusion A short
      term administration of parecoxib and celecoxib aids in the prevention of HO after
      acetabular fractures surgery.

PMID- 28500437
TI  - An evaluation of the translation of continuing education into diabetes public
      health care by pharmacists.
AB  - Background Pharmacists are assuming greater public health roles and partaking in
      continuing education to advance knowledge and skills necessary for the provision
      of this patient care. Objective We sought to determine what conditions in a
      Middle East context influence how community pharmacists actually incorporate new
      information into practice. Setting Community pharmacies in Qatar. Methods A
      continuing professional development (CPD) program regarding the management of
      fasting diabetes patients during Ramadan was developed and delivered.
      Participants then maintained a record of their patient encounters when attempting
      to screen fasting diabetes patients for risk and offer medication, lifestyle, and
      monitoring advice. Diary entries were coded using inductive methods and follow-up
      focus group discussion was conducted to further corroborate the thematic
      analysis. Main outcome measure Facilitators and barriers to care. Results Forty
      one pharmacists attended the CPD program and 35 subsequently made at least one
      diary entry during the 3-weeks preceding and during Ramadan. One-hundred and
      forty-eight submitted records and the transcript of one focus group (n = 6) were
      analyzed. Three main factors were found to influence pharmacists' ability to
      engage use new knowledge and skills: situational, patient, and pharmacist.
      Patient reception was the overwhelming influence whereby positive interactions
      encouraged pharmacists to continue screening and counseling attempts, but
      difficult encounters were negative reinforcing stimuli in almost equal measure.
      Conclusion In this Middle East setting, environmental factors play a considerable
      role in the pharmacists' ability to engage in public health care and reinforce
      that continuing education for health professionals must be closely aligned with
      the realities of practice and purposefully considered as part of its evaluation.

PMID- 28500440
TI  - Alternative Models to Hodgkin-Huxley Equations.
AB  - The Hodgkin and Huxley equations have served as the benchmark model in
      electrophysiology since 1950s. But it suffers from four major drawbacks. Firstly,
      it is only phenomenological not mechanistic. Secondly, it fails to exhibit the
      all-or-nothing firing mechanism for action potential generation. Thirdly, it
      lacks a theory for ion channel opening and closing activation across the cell
      membrane. Fourthly, it does not count for the phenomenon of voltage-gating which
      is vitally important for action potential generation. In this paper, a
      mathematical model for excitable membranes is constructed by introducing circuit
      characteristics for ion pump exchange, ion channel activation, and voltage
      gating. It is demonstrated that the model is capable of re-establishing the
      Nernst resting potentials, explicitly exhibiting the all-or-nothing firing
      mechanism, and most important of all, filling the long-lasting theoretical gap by
      a unified theory on ion channel activation and voltage-gating. It is also
      demonstrated that the new model has one half fewer parameters but fits
      significantly better to experiment than the HH model does. The new model can be
      considered as an alternative template for neurons and excitable membranes when
      one looks for simpler models for mathematical studies and for forming large
      networks with fewer parameters.

PMID- 28500439
TI  - Effect of basal forebrain stimulation on extracellular acetylcholine release and
      blood flow in the olfactory bulb.
AB  - The olfactory bulb receives cholinergic basal forebrain input, as does the
      neocortex; however, the in vivo physiological functions regarding the release of
      extracellular acetylcholine and regulation of regional blood flow in the
      olfactory bulb are unclear. We used in vivo microdialysis to measure the
      extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized
      rats. Focal chemical stimulation by microinjection of L-glutamate into the
      horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which
      is the main source of cholinergic input to the olfactory bulb, increased
      extracellular acetylcholine release in the ipsilateral olfactory bulb. When the
      regional cerebral blood flow was measured using laser speckle contrast imaging,
      the focal chemical stimulation of the HDB did not significantly alter the blood
      flow in the olfactory bulb, while increases were observed in the neocortex. Our
      results suggest a functional difference between the olfactory bulb and neocortex
      regarding cerebral blood flow regulation through the release of acetylcholine by
      cholinergic basal forebrain input.

PMID- 28500441
TI  - Route simulations, compass mechanisms and long-distance migration flights in
      birds.
AB  - Bird migration has fascinated humans for centuries and routes crossing the globe
      are now starting to be revealed by advanced tracking technology. A central
      question is what compass mechanism, celestial or geomagnetic, is activated during
      these long flights. Different approaches based on the geometry of flight routes
      across the globe and route simulations based on predictions from compass
      mechanisms with or without including the effect of winds have been used to try to
      answer this question with varying results. A major focus has been use of
      orthodromic (great circle) and loxodromic (rhumbline) routes using celestial
      information, while geomagnetic information has been proposed for both a magnetic
      loxodromic route and a magnetoclinic route. Here, we review previous results and
      evaluate if one or several alternative compass mechanisms can explain migration
      routes in birds. We found that most cases could be explained by magnetoclinic
      routes (up to 73% of the cases), while the sun compas s could explain only 50%.
      Both magnetic and geographic loxodromes could explain <25% of the routes. The
      magnetoclinic route functioned across latitudes (1 degrees S-74 degrees N), while
      the sun compass only worked in the high Arctic (61-69 degrees N). We discuss the
      results with respect to orientation challenges and availability of orientation
      cues.

PMID- 28500442
TI  - Drosophila Rhodopsin 7 can partially replace the structural role of Rhodopsin 1,
      but not its physiological function.
AB  - Rhodopsin 7 (Rh7), a new invertebrate Rhodopsin gene, was discovered in the
      genome of Drosophila melanogaster in 2000 and thought to encode for a functional
      Rhodopsin protein. Indeed, Rh7 exhibits most hallmarks of the known Rhodopsins,
      except for the G-protein-activating QAKK motif in the third cytoplasmic loop that
      is absent in Rh7. Here, we show that Rh7 can partially substitute Rh1 in the
      outer receptor cells (R1-6) for rhabdomere maintenance, but that it cannot
      activate the phototransduction cascade in these cells. This speaks against a role
      of Rh7 as photopigment in R1-6, but does not exclude that it works in the inner
      photoreceptor cells.

PMID- 28500443
TI  - Genome characterization of a novel megrivirus-related avian picornavirus from a
      carnivorous wild bird, western marsh harrier (Circus aeruginosus).
AB  - In this study, the complete genome of a novel picornavirus called harrier
      picornavirus 1 (HaPV-1) strain harrier/MR-01/HUN/2014 (KY488458) was sequenced
      and analysed from a cloacal sample of a threatened, carnivorous wild bird,
      western marsh harrier (Circus aeruginosus). HaPV-1 was detectable from 2 of the 3
      samples from harriers. HaPV-1 is phylogenetically related to megriviruses (genus
      Megrivirus) from domestic chicken, turkey and duck, showing a similar genome
      organization pattern; it also has an avian picornavirus-like "Unit A" motif in
      the 3' UTR. Unlike the type-IV internal ribosomal entry site (IRES) of
      megriviruses, HaPV-1 is predicted to contain a type-II-like IRES, suggesting
      modular exchange of IRES elements between picornavirus genomes.

PMID- 28500444
TI  - Development of a recombinase polymerase amplification assay for the diagnosis of
      banana bunchy top virus in different banana cultivars.
AB  - Recombinase polymerase amplification (RPA) is a rapid, isothermal amplification
      method with high specificity and sensitivity. In this study, an assay was
      developed and evaluated for the detection of banana bunchy top virus (BBTV) in
      infected banana plants. Three oligonucleotide primer pairs were designed from the
      replicase initiator protein gene sequences of BBTV to function both in RPA as
      well as in polymerase chain reaction (PCR). A total of 133 symptomatic as well as
      asymptomatic banana leaf samples from various cultivars were collected from the
      different regions of India and evaluated for BBTV infection using the RPA assay.
      BBTV was efficiently detected using crude leaf sap in RPA and the results
      obtained were consistent with PCR-based detection using purified DNA as template.
      To our knowledge, this is the first report of reliable diagnosis of BBTV
      infection by RPA using crude leaf sap as a template.

PMID- 28500445
TI  - Genetic diversity and evolutionary characteristics of type 2 porcine reproductive
      and respiratory syndrome virus in southeastern China from 2009 to 2014.
AB  - The objective of this study was to assess the genetic diversity of porcine
      reproductive and respiratory syndrome virus circulating in Fujian province
      (southeastern China). Based on 53 ORF5 nucleotide sequences collected from nine
      sites, both highly pathogenic (sublineage 8.7) and lineage 1 strains were
      circulating in Fujian in 2009-2014 along with lineages 3 and 5.1. Notably, the
      lineage 1 strains were closely related to the NADC30 strain circulating in North
      America and were the predominant strains in 2014. In addition, we found that
      nonstructural protein 2 (NSP2) was the most variable nonstructural protein in
      Fujian isolates, with a 36-amino-acid (aa) insertion and seven different
      deletions detected in the 53 sequences examined. Similarly, analysis of GP5 amino
      acid sequences showed that the isolates were highly variable in primary
      neutralizing epitopes. Interesting, FJ3.2 and FJ7-2 strains have the mutation
      N44K, but they exhibited high replication and high titers in MARC-145 and PAM
      cells. The complete genome sequences determined for 12 type 2 isolates were 82.1
      99.3% identical and were 15,016-15,407 nucleotides (nt), in length excluding the
      poly(A) tail. The strains also shared 88.2-99.4% identity with strain VR2332 (the
      prototype North American strain), 83.4-99.2% identity with strain JXA1 (the
      prototype high-pathogenicity Chinese strain), 88.2-97.1% identity with strain CH
      1a (the prototype classical Chinese strain), and 82.9-97.1% identity with strain
      NADC30 (the prototype NADC30-like strain). Strikingly, phylogenetic and molecular
      evolutionary analyses indicated that strain FJW05 is a spontaneous recombinant
      between a circulating lineage 1 virus and the vaccine strain JXA1-R, which is
      derived from the highly pathogenic strain JXA-1. Collectively, the data highlight
      the epidemiology of porcine reproductive and respiratory syndrome in Fujian and
      may aid in selecting a suitable vaccine for use on pig farms.

PMID- 28500446
TI  - A Portuguese rapid-onset dystonia-parkinsonism case with atypical features.

PMID- 28500447
TI  - [Certification guidelines and qualification courses].
AB  - German regulations require a license for using ionizing radiation in medicine.
      This license-called "Fachkunde"-varies for different medical procedures such as
      CT, fluoroscopy, radiography, or mammography. The required frequencies and
      training times also vary for different medical disciplines such as radiology,
      cardiology, vascular surgery, traumatology, nuclear medicine, and radiotherapy,
      among others. The quality criteria for a specific license require a minimum
      training time under supervision and a minimum frequency of a wide range of
      procedures. Depending on the radiation doses used and the complexity of
      procedures performed, this may go up to 5000 examinations and 36 months for a
      radiology resident. A refresher course is mandatory every 5 years.

PMID- 28500448
TI  - Bone Loss After Denosumab: Only Partial Protection with Zoledronate.
AB  - A case series of six women with postmenopausal osteoporosis who had received
      continuous denosumab for 7 years and were then given a single infusion of
      zoledronate (5 mg) is reported. During denosumab treatment, bone mineral density
      (BMD) in the spine increased 18.5% (P = 0.006), and total hip BMD by 6.9% (P =
      0.03). Post-zoledronate BMDs were measured 18-23 months after treatment, and
      there were significant declines at each site (P spine = 0.043, P hip = 0.005).
      Spine BMD remained significantly above the pre-denosumab baseline (+9.3%, P =
      0.003), but hip BMD was not significantly different from baseline (-2.9%). At the
      time of post-zoledronate BMD measurements, serum PINP levels were between 39 and
      60 MUg/L (mean 52 MUg/L), suggesting that the zoledronate treatment had not
      adequately inhibited bone turnover. It is concluded that this regimen of
      zoledronate administration is not adequate to preserve the BMD gains that result
      from long-term denosumab treatment.

PMID- 28500449
TI  - Concentration polarization phenomenon in the case of mechanical pressure
      difference on the membrane.
AB  - We analyzed the transport of KCl solutions through the bacterial cellulose
      membrane and concentration boundary layers (CBLs) near membrane with pressure
      differences on the membrane. The membrane was located in horizontal-plane between
      two chambers with different KCL solutions. The membrane was located in horizontal
      plane between two chambers with different KCL solutions. As results from the
      elaborated model, gradient of KCL concentration in CBLs is maximal at membrane
      surfaces in the case when pressure difference on the membrane equals zero. The
      amplitude of this maximum decreases with time of CBLs buildup. Application of
      mechanical pressure gradient in the direction of gradient of osmotic pressure on
      the membrane causes a shift of this maximum into the chamber with lower
      concentration. In turn, application of mechanical pressure gradient directed
      opposite to the gradient of osmotic pressure causes the appearance of maximum of
      concentration gradient in chamber with higher concentration. Besides, the
      increase of time of CBLs buildup entails a decrease of peak height and shift of
      this peak further from the membrane. Similar behavior is observed for
      distribution of energy dissipation in CBLs but for pressure difference on the
      membrane equal to zero the maximum of energy dissipation is observed in the
      chamber with lower concentration. We also measured time characteristics of
      voltage in the membrane system with greater KCl concentrations over the membrane.
      We can state that mechanical pressure difference on the membrane can suppress or
      strengthen hydrodynamic instabilities visible as pulsations of measured voltage.
      Additionally, time of appearance of voltage pulsations, its amplitude, and
      frequency depend on mechanical pressure differences on the membrane and initial
      quotient of KCl concentrations in chambers.

PMID- 28500450
TI  - Genetic variation in matrix metalloproteinase MMP2 and MMP9 as a risk factor for
      idiopathic recurrent spontaneous abortions in an Indian population.
AB  - PURPOSE: Matrix metalloproteinases, MMP2 and MMP9, are found to have an important
      role during ovulation and pregnancy because of their capacity to degrade
      components of the extracellular matrix (ECM) thereby facilitating cell migration
      and angiogenesis. In this respect, the aim of the present study was to evaluate
      the association of the promoter polymorphisms -1306 C > T and -1562 C/T in MMP2
      and MMP9 respectively with couples diagnosed with idiopathic recurrent
      spontaneous abortions (IRSA). The expression levels of these two genes were also
      studied in fetal tissue. METHODS: In this case control study, a total of 35
      couples with at least three consecutive IRSA and 35 fertile couples were
      included. Genotype analysis was performed using polymerase chain reaction and
      Sanger sequencing. RESULTS: No statistically significant differences were found
      in distribution of MMP2-1306C/T and MMP9-1562C/T genotypes in the three groups
      between the cases and controls. CONCLUSION: Further genetic association studies
      on a larger number of IRSA couples, as well as evaluation of more MMP
      polymorphisms and their expression profiling are needed to establish the
      potential role of MMP polymorphisms in IRSA.

PMID- 28500452
TI  - Erythroblastopenia in a critically ill influenza patient.

PMID- 28500451
TI  - Pregnancy rates for single embryo transfer (SET) of day 5 and day 6 blastocysts
      after cryopreservation by vitrification and slow freeze.
AB  - PURPOSE: The purpose of this study was to compare clinical and ongoing pregnancy
      rates in cycles with single embryo transfer (SET) of blastocysts cryopreserved on
      day 5 or day 6. Our aim was to determine whether day 6 blastocysts perform
      adequately to recommend SET. METHODS: Retrospective cohort study including 468
      transfer cycles for 392 women younger than age 38 undergoing SET at a university
      affiliated IVF clinic in the USA. A total of 261 day 5 blastocysts and 207 day 6
      blastocysts for frozen-thawed SET between 2010 and 2016 were analyzed. Data
      included cryopreservation by both a slow freeze method and vitrification.
      RESULTS: In total, 59.0% of day 5 SET cycles resulted in a clinical pregnancy
      compared to 54.1% of day 6 blastocysts (p = 0.54). Ongoing pregnancy rates from
      day 5 frozen-thawed blastocysts (51.7%) were comparable to day 6 (44.9%, p =
      0.14). When looking at vitrified blastocysts only, there were no significant
      differences between day 5 and day 6 blastocysts, with a clinical pregnancy rate
      of 69.2% for day 5 and 72.5% for day 6 (p = 0.68). CONCLUSIONS: SETs of day 6
      cryopreserved blastocysts resulted in similar clinical and ongoing pregnancy
      rates compared to day 5, particularly after vitrification.

PMID- 28500453
TI  - What does it mean for a critically ill patient to fare well?

PMID- 28500454
TI  - Extracorporeal membrane oxygenation for poisoning in adult patients: outcomes and
      predictors of mortality.

PMID- 28500457
TI  - An alternative technique for greater tuberosity fractures: use of the mesh plate.
AB  - INTRODUCTION: Isolated greater tuberosity (GT) fractures (AO 11-A1) tend to occur
      in the younger patient population and are poorly managed by most precontoured
      proximal humerus locking plates. The goal of this study was to identify and
      assess an alternative treatment strategy for greater tuberosity fractures.
      MATERIALS AND METHODS: A retrospective review of all cases of isolated greater
      tuberosity fractures treated with a 2.4/2.7 mesh plate (Synthes) between 2010 and
      2015 was conducted. Patient demographics, operative reports, and clinical notes
      were reviewed. The time to radiographic union was assessed. Clinical outcomes
      were retrieved from patients at their follow-up visits or via mailed Disabilities
      of the Arm, Shoulder, Hand (DASH) questionnaires. RESULTS: Ten patients with
      isolated GT fractures treated with mesh plating were identified with an average
      age of 47.1 years. The average radiographic follow-up was 7.2 months and the
      average clinical follow-up was 8.0 months. The mean time to union was 8.5 weeks.
      Two patients underwent elective hardware removal. The mean DASH at final follow
      up was 28.2 (+/-22.4), while the mean DASH work was 13.6 (+/-19.1). CONCLUSION:
      We have identified a viable alternative treatment option for the surgical
      management of isolated greater tuberosity fractures using a mesh plate that can
      be contoured to the patient's anatomy. Surgeons should be aware of this option
      for select patients.

PMID- 28500456
TI  - Sex differences in spatial accuracy relate to the neural activation of
      antagonistic muscles in young adults.
AB  - Sex is an important physiological variable of behavior, but its effect on motor
      control remains poorly understood. Some evidence suggests that women exhibit
      greater variability during constant contractions and poorer accuracy during goal
      directed tasks. However, it remains unclear whether motor output variability or
      altered muscle activation impairs accuracy in women. Here, we examine sex
      differences in endpoint accuracy during ankle goal-directed movements and the
      activity of the antagonistic muscles. Ten women (23.1 +/- 5.1 years) and 10 men
      (23 +/- 3.7 years) aimed to match a target (9 degrees  in 180 ms) with ankle
      dorsiflexion. Participants performed 50 trials and we recorded the endpoint
      accuracy and the electromyographic (EMG) activity of the primary agonist
      (Tibialis Anterior; TA) and antagonist (Soleus; SOL) muscles. Women exhibited
      greater spatial inaccuracy (Position error: t = -2.65, P = 0.016) but not
      temporal inaccuracy relative to men. The motor output variability was similar for
      the two sexes (P > 0.2). The spatial inaccuracy in women was related to greater
      variability in the coordination of the antagonistic muscles (R 2 0.19, P = 0.03).
      These findings suggest that women are spatially less accurate than men during
      fast goal-directed movements likely due to an altered activation of the
      antagonistic muscles.

PMID- 28500455
TI  - The intensive care medicine research agenda on septic shock.
AB  - Septic shock remains a global health challenge with millions of cases every year,
      high rates of mortality and morbidity, impaired quality of life among survivors
      and relatives, and high resource use both in developed and developing nations.
      Care and outcomes are improving through organisational initiatives and updated
      clinical practice guidelines based on clinical research mainly carried out by
      large collaborative networks. This progress is likely to continue through the
      collaborative work of the established and merging trials groups in many parts of
      the world and through refined trial methodology and translational work. In this
      review, international experts summarize the current position of clinical research
      in septic shock and propose a research agenda to advance this field.

PMID- 28500458
TI  - Occurrence of Vascular Lake Phenomenon as a Predictor of Improved Tumor Response
      in HCC Patients That Underwent DEB-TACE.
AB  - PURPOSE: To evaluate incidence and predictive factors for the vascular lake
      phenomenon (VLP), as well as to compare local and overall tumor response in
      patients with and without VLP induced during DEB-TACE for HCC. METHODS: A total
      of 200 consecutive patients with 323 HCC nodules underwent first-session DEB-TACE
      from 2011 to 2014. Patients were divided in two groups, according to the presence
      of the VLP during DEB-TACE. Pre- and post-treatment imaging studies (CT or MRI)
      were performed. Primary endpoint was assessment of tumor response, evaluated by
      mRECIST. Comparison of response rates between the VLP group and the non-VLP group
      was performed. Secondary endpoints were the determination of incidence rate and
      predictive factors for the VLP. RESULTS: The VLP was observed in 39/323 (12.1%)
      of the nodules treated. At multivariate logistic regression analysis, tumor size
      >=3 cm in diameter (OR 13.95; 95% CI 3.60-54.05), presence of a pseudocapsule (OR
      6.67; 95% CI 1.45-30.59) and alpha-fetoprotein levels (OR 1.004; 95% CI 1.000
      1.007) remained predictive for the VLP occurrence. On a nodule-based analysis (p
      < 0.001), target lesion response analysis (p = 0.003) and overall response
      analysis (p = 0.004) the VLP group presented a higher objective response rate
      than the non-VLP group. CONCLUSION: VLP is observed in 12% of the patients and
      happens more frequently in large and encapsulated tumors. It seems to be
      associated with better local and overall responses in HCC patients who underwent
      DEB-TACE.

PMID- 28500459
TI  - Personalized Feedback on Staff Dose in Fluoroscopy-Guided Interventions: A New
      Era in Radiation Dose Monitoring.
AB  - PURPOSE: Radiation safety and protection are a key component of fluoroscopy
      guided interventions. We hypothesize that providing weekly personal dose feedback
      will increase radiation awareness and ultimately will lead to optimized behavior.
      Therefore, we designed and implemented a personalized feedback of procedure and
      personal doses for medical staff involved in fluoroscopy-guided interventions.
      MATERIALS AND METHODS: Medical staff (physicians and technicians, n = 27)
      involved in fluoroscopy-guided interventions were equipped with electronic
      personal dose meters (PDMs). Procedure dose data including the dose area product
      and effective doses from PDMs were prospectively monitored for each consecutive
      procedure over an 8-month period (n = 1082). A personalized feedback form was
      designed displaying for each staff individually the personal dose per procedure,
      as well as relative and cumulative doses. This study consisted of two phases: (1)
      1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months:
      Staff received weekly individual dose feedback (n = 381). An anonymous evaluation
      was performed on the feedback and occupational dose. RESULTS: Personalized
      feedback was scored valuable by 76% of the staff and increased radiation dose
      awareness for 71%. 57 and 52% reported an increased feeling of occupational
      safety and changing their behavior because of personalized feedback,
      respectively. For technicians, the normalized dose was significantly lower in the
      feedback phase compared to the prefeedback phase: [median (IQR) normalized dose
      (phase 1) 0.12 (0.04-0.50) uSv/Gy cm2 versus (phase 2) 0.08 (0.02-0.24) uSv/Gy
      cm2, p = 0.002]. CONCLUSION: Personalized dose feedback increases radiation
      awareness and safety and can be provided to staff involved in fluoroscopy-guided
      interventions.

PMID- 28500460
TI  - Prophylactic Temporary Occlusion of the Cystic Artery Using a Fibered Detachable
      Coil During 90Y Radioembolization.
AB  - PURPOSE: To address the feasibility of prophylactic temporary occlusion of the
      cystic artery using a detachable coil during 90Y radioembolization. MATERIALS AND
      METHODS: From January 2012 to October 2016, nine patients underwent temporary
      occlusion of the cystic artery during 90Y radioembolization. Based on the
      planning hepatic angiography, a detachable coil was deployed into the cystic
      artery, which arose from a more distal level (e.g., right anterior hepatic
      artery) than its usual origin, but the proximal 1 cm was left inside the
      microcatheter. 90Y microspheres were infused proximal to the cystic artery where
      the 99mTc-MAA had been infused, and then the coil was retrieved. Afterward, the
      patients underwent PET/CT imaging. Medical records were reviewed, and the
      differences in the uptake of 99mTc-MAA and 90Y microspheres in the gallbladder
      were evaluated using Wilcoxon's signed-rank test. RESULTS: Temporary placement of
      a detachable coil was feasible in all cases. On the angiograms obtained after
      detachable coil placement, the distal cystic artery and gallbladder were
      partially identifiable in eight of the nine (88.8%) patients, but fully restored
      after the removal of the coils in all cases. The proportional uptake of 99mTc-MAA
      (mean, 4.35%) and 90Y (mean, 0.90%) in the gallbladder was significantly
      different due to the temporary occlusion of the cystic artery (p = 0.004). No
      clinical complications were identified for three months after the procedure.
      CONCLUSION: Temporary occlusion of the cystic artery using a detachable coil
      appeared to be feasible and effective in reducing 90Y uptake in the gallbladder.

PMID- 28500461
TI  - Predicting Success in Percutaneous Transhepatic Biliary Drainage.
AB  - PURPOSE: To develop a model to predict successful bilirubin decrease following
      percutaneous biliary drain placement. METHODS: A total of 257 patients who were
      identified having undergone percutaneous transhepatic biliary drain placement
      (PTBD) at our institution between 2002 and 2013 had their medical records and
      imaging reviewed. Of those, 190 of these patients met criteria and were used in
      the analysis. A regression model was performed on logarithm-transformed collected
      variables to predict post-drainage logarithmic transformed total bilirubin
      levels. A stepwise variable selection method based on Schwarz Bayesian
      Information Criterion was used to select the most closely associated variables.
      The model was validated with a Monte Carlo simulation. A short program was
      developed to calculate the point estimate using the model developed and compared
      to actual values. RESULTS: The variables that best predicted bilirubin reduction
      were initial Tbl (PrTbl), INR and ALT. The selected model had a root mean squared
      error of 0.8. The model had a negative predictive value (PoTbl is below 2 mg/dL)
      of 83%. CONCLUSIONS: PTBD may not achieve decreasing bilirubin in patients with a
      malignant obstruction. This is an initial model that can help determine which
      patients may not benefit from PTBD placement. With more patients, the model's
      validity can be increased and provide useful clinical determinant to aide patient
      care.

PMID- 28500462
TI  - Perfusion index and left ventricular output correlation in healthy term infants.
AB  - : Perfusion index (PI) is a non-invasive marker of peripheral perfusion which is
      detected by an oximeter. We aimed to assess the correlation between PI and left
      ventricular output (LVO) in healthy term infants at the time of the screening for
      congenital heart disease (CHD). PI was measured at 48+/-2 h of life in the
      infant's right hand (PIrh) and in one foot (PIf) contemporary to SpO2 for CHD
      screening. Heart ultrasound was performed immediately after the screening
      procedure for measuring LVO. Forty-nine healthy term infants were studied. PIrh
      and PIf were 1.9 +/- 0.6 and 1.9 +/- 0.8, respectively, and their values were
      significantly correlated (p < 0.0001) with a coefficient r = 0.8. Bland-Altman
      analysis shows a mean difference of -0.06 +/- 0.47 (95%LOA -0.98-0.86). PIrh
      correlates with LVO (r = 0.68) and LVO/kg (r = 0.61) with an increase of 151
      mL/min (95%CI 103-198) of LVO and 42 mL/kg/min (95%CI 26-58) of LVO/kg per point
      of PIrh. PIf correlates with LVO (r = 0.74) and LVO/kg (r = 0.73) with an
      increase of 123 mL/min (95%CI 90-155) of LVO and 37 mL/kg/min (95%CI 27-47) of
      LVO/kg per point of PIf. CONCLUSION: PI is significantly correlated with LVO in
      healthy term infants. These results support the theoretical potential role of PI
      in the CHD screening. What is Known: * Perfusion index is an indirect measure of
      perfusion which depends on cardiac output and peripheral vascular resistance
      whose normal values have been documented in term and preterm infants in the first
      days of life. * Perfusion index has been proposed for the screening of congenital
      heart disease with duct-dependent systemic circulation in term infants. What is
      New: * Perfusion index shows a significant correlation with the left ventricular
      output in term infants at the moment of the screening for congenital heart
      disease. * Perfusion index might have a theoretical role in improving the
      accuracy of pulse oximetry in the screening of CHD associated to low systemic
      flow.

PMID- 28500463
TI  - Comparison of four different intraosseous access devices during simulated
      pediatric resuscitation. A randomized crossover manikin trial.
AB  - : The aim of the study was to compare the success rate, procedure time, and user
      satisfaction of pediatric NIOTM compared to Pediatric BIG(r), EZ-IO(r), and
      Jamshidi intraosseous access devices. This was a randomized, crossover manikin
      trial with 87 paramedics. The correct location of intraosseous access when using
      NIO, BIG, EZ-IO, and Jamshidi was varied and was respectively 100, 90, 90, and
      90%. The time required to obtain intravascular access (time T1) in the case of
      NIO, BIG, EZ-IO, and Jamshidi was varied and amounted to 9 s [IQR, 8-12] for NIO,
      12 s [IQR, 9-16] for BIG, 13.5 s [IQR, 11-17] for the EZ-IO, and 15 s [IQR, 13
      19] for Jamshidi. The paramedics evaluated each device on the subjective ease
      with which they performed the procedures. The intraosseous device, which proved
      the easiest to use was NIO, which in the case of CPR received a median rating of
      1.5 (IQR, 0.5-1.5) points. CONCLUSION: Our study found that NIO(r) is superior to
      BIG(r), EZ-IO(r), and Jamshidi. NIO(r) achieved the highest first attempt success
      rate. NIO(r) also required the least time to insert and easiest to operate even
      by novice users. Further study is needed to test our findings in cadavers or
      human subjects. Based on our findings, NIO(r) is a promising intraosseous device
      for use in pediatric resuscitation. What is Known: * Venous access in acutely ill
      pediatric patients, such as those undergoing cardiopulmonary resuscitation, is
      needed for prompt administration of drugs and fluids. * Intraosseous access is
      recommended by American Heart Association and European Resuscitation council if
      vascular access is not readily obtainable to prevent delay in treatment. What is
      New: * This simulated pediatric resuscitation compared performance of four
      commercially available pediatric intraosseous devices in a manikin model. *
      NIO(r) outperformed BIG(r), EZ-IO(r), and Jamshidi in first attempt success rates
      and time of procedure among novice users.

PMID- 28500465
TI  - The Information Sharing Statement Grows Some Teeth.

PMID- 28500466
TI  - A three-dimensional pelvic model made with a three-dimensional printer:
      applications for laparoscopic surgery to treat rectal cancer.
AB  - To help understand the three-dimensional (3D) spatial relationships among the
      highly complex structures of the pelvis, we made a novel 3D pelvic model with a
      3D printing system. We created two pelvic models including the muscles, vessels,
      nerves, and urogenital organs; the first based on the pelvic anatomy of a healthy
      male volunteer and the second on the pelvic anatomy of a female volunteer with
      rectal cancer. The models clearly demonstrated the complicated spatial
      relationships between anatomical structures in the pelvis. Surgeons could use
      these models to improve their spatial understanding of pelvic anatomy, which
      could consequently improve the safety and efficiency of laparoscopic rectal
      cancer surgery.

PMID- 28500464
TI  - Global skin colour prediction from DNA.
AB  - Human skin colour is highly heritable and externally visible with relevance in
      medical, forensic, and anthropological genetics. Although eye and hair colour can
      already be predicted with high accuracies from small sets of carefully selected
      DNA markers, knowledge about the genetic predictability of skin colour is
      limited. Here, we investigate the skin colour predictive value of 77 single
      nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with
      human pigmentation using 2025 individuals from 31 global populations. We
      identified a minimal set of 36 highly informative skin colour predictive SNPs and
      developed a statistical prediction model capable of skin colour prediction on a
      global scale. Average cross-validated prediction accuracies expressed as area
      under the receiver-operating characteristic curve (AUC) +/- standard deviation
      were 0.97 +/- 0.02 for Light, 0.83 +/- 0.11 for Dark, and 0.96 +/- 0.03 for Dark
      Black. When using a 5-category, this resulted in 0.74 +/- 0.05 for Very Pale,
      0.72 +/- 0.03 for Pale, 0.73 +/- 0.03 for Intermediate, 0.87+/-0.1 for Dark, and
      0.97 +/- 0.03 for Dark-Black. A comparative analysis in 194 independent samples
      from 17 populations demonstrated that our model outperformed a previously
      proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White,
      comparable at the intermediate level of 0.63 and 0.62, respectively, and a large
      increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the
      chosen DNA markers and prediction model, particularly the 5-category level; allow
      skin colour predictions within and between continental regions for the first
      time, which will serve as a valuable resource for future applications in forensic
      and anthropologic genetics.

PMID- 28500467
TI  - Psoriasis in children with type 1 diabetes: A new comorbidity to be considered?

PMID- 28500468
TI  - Rickettsia spp. in Dermacentor marginatus ticks: analysis of the host-vector
      pathogen interactions in a northern Mediterranean area.
AB  - In this work, we have analyzed the key features of Rickettsia spp. maintenance in
      Dermacentor marginatus ticks in four regions of the northern Mediterranean area,
      where extensive investigations are currently lacking. For this purpose, 380 adult
      D. marginatus ticks were collected from vegetation and wild ungulates during a 3
      year study. A host-vector-pathogen interaction approach was applied to
      investigate the key components of the disease systems and evaluate their
      respective weight in the intensity of infection in natural foci. A high
      variability in the R. slovaca infection rate among sampling sites was observed,
      whereas R. raoultii was sporadically present and at low infection rates.
      Dermacentor marginatus presence was confirmed in all the investigated regions.
      The local wild boar population showed a strong association with adult D.
      marginatus ticks. The results of this investigation suggest that wild boars not
      only maintain D. marginatus populations by feeding adult ticks, but may also have
      a potential role in the eco-epidemiology of rickettsioses, as carriers of
      rickettsiae-infected ticks. The public health implications of these results are
      discussed.

PMID- 28500469
TI  - Aggression Predicts Changes in Peer Victimization that Vary by Form and Function.
AB  - Peer victimization is predictive of serious problems in adjustment, especially
      among children who are both victimized and aggressive. This study investigated
      how different types of aggression contribute to later victimization.
      Specifically, we examined prospective relationships between the types of
      aggression that children perpetrated and the types that they experienced at the
      hands of others. Trained observers coded schoolyard behavior of 553 children in
      grades 3-6 during the initial year of a bullying intervention program. Both
      observed aggression and victimization were specified by form (direct, indirect)
      and function (proactive, reactive). Total hourly rates of victimization were
      highest in the upper grades. Direct-reactive aggression uniquely predicted
      increases in victimization, while direct-proactive aggression predicted
      decreases, particularly in direct-proactive victimization. Indirect-proactive
      aggression (e.g., derogatory gossip) predicted increases in indirect-proactive
      victimization only in the control group. Indirect-reactive aggression and
      victimization occurred too rarely to detect change. Aggression-victimization
      relationships did not differ for boys and girls. Discussion considers why
      children might risk direct reactive aggression in the face of increased
      victimization. Different sequelae for different forms and functions of aggression
      highlight the need to resolve theoretical ambiguities in defining proactive and
      reactive aggression.

PMID- 28500470
TI  - Neural Correlates of Emotion Reactivity and Regulation in Young Children with
      ADHD Symptoms.
AB  - Emotion reactivity and regulation are frequently impaired in individuals with
      attention-deficit/hyperactivity disorder (ADHD), yet few studies have examined
      these factors in young children with ADHD, and none have explored the neural
      correlates of emotion reactivity and regulation in this group through event
      related potentials (ERPs). Children aged 4 to 7 with (n = 25; 18 boys) and
      without (n = 29; 20 boys) ADHD symptoms completed an attention task composed of
      four blocks: baseline, frustration, suppression, and recovery. In the frustration
      and suppression blocks, negative affect was induced by false negative feedback.
      During the suppression block, children were asked to suppress emotional
      expressions. Neural reactivity, assessed via the N2 and P3 components, suggests
      that children with ADHD symptoms processed the emotional induction differently
      than typically developing (TD) children. TD children demonstrated decreased N2
      and increased P3 amplitudes at frontal and frontocentral regions across task
      conditions whereas children with ADHD symptoms showed relatively stable N2 and P3
      amplitudes. This pattern suggests that young children with ADHD symptoms are not
      as effective as their TD peers in modulating attention allocation and cognitive
      control in emotionally laden situations. The present study underscores that
      emotional contexts may exacerbate attentional control deficits in young children
      with ADHD symptoms.

PMID- 28500471
TI  - W-enriched satellite sequence in the Indian meal moth, Plodia interpunctella
      (Lepidoptera, Pyralidae).
AB  - The W chromosome of most lepidopteran species represents the largest
      heterochromatin entity in the female genome. Although satellite DNA is a typical
      component of constitutive heterochromatin, there are only a few known satellite
      DNAs (satDNAs) located on the W chromosome in moths and butterflies. In this
      study, we isolated and characterized new satDNA (PiSAT1) from microdissected W
      chromosomes of the Indian meal moth, Plodia interpunctella. Even though the
      PiSAT1 is mainly localized near the female-specific segment of the W chromosome,
      short arrays of this satDNA also occur on autosomes and/or the Z chromosome.
      Probably due to the predominant location in the non-recombining part of the
      genome, PiSAT1 exhibits a relatively large nucleotide variability in its
      monomers. However, at least a part of all predicted functional motifs is located
      in conserved regions. Moreover, we detected polyadenylated transcripts of PiSAT1
      in all developmental stages and in both sexes (female and male larvae, pupae and
      adults). Our results suggest a potential structural and functional role of PiSAT1
      in the P. interpunctella genome, which is consistent with accumulating evidence
      for the important role of satDNAs in eukaryotic genomes.

PMID- 28500473
TI  - Orchid Bee (Apidae: Euglossini) Communities in Atlantic Forest Remnants and
      Restored Areas in Parana State, Brazil.
AB  - In this study, we compare orchid bee communities surveyed in four forest remnants
      of the Atlantic Forest and four reforested areas characterized by seasonal semi
      deciduous forest vegetation in different successional stages (mature and
      secondary vegetation), located in southern Brazil. The sizes of forest remnants
      and reforested areas varied from 32.1 to 583.9 ha and from 11.3 to 33.3 ha,
      respectively. All reforested areas were located near one forest remnant. During
      samplings, totaling nine per study area, euglossine males were attracted to eight
      scent baits and captured with bait trap and entomological nets. Each forest
      remnant and its respective reforested area were sampled simultaneously by two
      collectors. We collected 435 males belonging to nine species of orchid bees
      distributed in four genera. The number of individuals and species did not differ
      significantly between different areas, except for a reforested area (size 33.3
      ha), which was located far from its respective forest remnant. Our findings also
      revealed an apparent association between an orchid bee species (Euglossa
      annectans Dressler 1982) and the most preserved area surveyed in our study,
      suggesting that this bee is a potential indicator of good habitat quality in
      recuperating or preserved areas. Our results suggest that reforested habitats
      located near forest remnants have a higher probability of having reinstated their
      euglossine communities.

PMID- 28500472
TI  - Impaired Interpretation of Others' Behavior is Associated with Difficulties in
      Recognizing Pragmatic Language in Patients with Schizophrenia.
AB  - Much attention has been paid to the pragmatic language function in schizophrenia.
      This study of Japanese patients with schizophrenia examined the relationship
      between impaired interpretation of the behaviors of other people in social
      contexts and the ability to recognize metaphor and irony. We assessed 34 patients
      with schizophrenia and 34 normal subjects using first- and second-order theory of
      mind tasks, the Metaphor and Sarcasm Scenario Test, and the Dewey Story Test
      (which tests the ability to judge others' social behaviors). We compared the
      performance between the groups and analyzed correlations between the tasks. All
      tasks revealed significant deficits in the patients compared with the controls.
      In the patient group, metaphor comprehension was correlated with the ability to
      judge normal behaviors, and irony comprehension was correlated with the ability
      to judge abnormal behaviors, suggesting that deficits of social cognition in
      schizophrenia include these two types of factors associated with pragmatic
      language.

PMID- 28500475
TI  - Mitteilungen der DGKFO.

PMID- 28500474
TI  - Comparisons of hospital output in Canada: national and international
      perspectives.
AB  - Current cost-based approach in measuring health care output does not allow
      decomposition of health care expenditure into price and output components. In
      this paper we propose an episode-based direction measurement method which closely
      resembles the concept of output in the system of national accounts. Using data
      from the Canadian Institute for Health Information, we calculate a quality
      unadjusted output index of the Canadian hospital sector for the periods 1996
      2005. The result shows that total output increases at an average annual growth
      rate of 1.49%. We expect that with the quality adjustment the actual rate is
      higher. This is in contrast with the long-held assumption that health care
      productivity growth is zero. Our results provide key information on the ongoing
      health care policy debate.

PMID- 28500477
TI  - Impact of a Program for the Management of Aggressive Behaviors on Seclusion and
      Restraint Use in Two High-Risk Units of a Mental Health Institute.
AB  - The Omega Program for the Management of Aggressive Behaviors aims to reduce
      patients' dangerous behaviors, towards themselves or others, and to reduce the
      use of seclusion and restraint (S/R). A previous study in a Mental Health
      Institute (Montreal, Canada) showed that implementing this program allowed
      employees of the intensive care and emergency units to gain confidence in coping
      with patients' aggressions and to reduce their psychological distress. The
      present study, conducted in the same high-risk units, assesses the effect of the
      program on S/R use. We hypothesize that the incidence and duration of S/R should
      diminish significantly following the implementation of the program in both units.
      This naturalistic, prospective study covered archival data between April 2010 and
      July 2014. Pre-training data (April 2010-December 2011) were compared to data
      during training (January 2012-October 2012) and to post-training data (November
      2012-July 2014) for both units. In the intensive care unit, we confirmed an
      increase of both mean daily number and duration of S/R by admissions in pre
      training, followed by a decrease during the training and post-training. In the
      emergency unit, a decreasing trend is seen during the entire period thus
      suggesting that the decrease in S/R may be independent of the training. These
      findings suggest that Omega is a promising intervention program to use in an
      intensive care unit. However, a more global approach, including institutional
      changes in culture and attitude, can be important factors to develop to increase
      the positive outcomes.

PMID- 28500476
TI  - Update on APOA5 Genetics: Toward a Better Understanding of Its Physiological
      Impact.
AB  - PURPOSE OF REVIEW: This review is intended to summarize the genetic studies
      published during the last 3 years that help us understand the physiology of apoAV
      and its clinical implications. RECENT FINDINGS: APOA5 is probably the gene with
      the strongest effect on triglyceride (TG) metabolism. APOA5 is almost exclusively
      expressed in the liver, and its product apoAV has a very low circulating
      concentration. New physiological roles of apoAV have been recently elucidated,
      such as control of chylomicron production in the intestine and TG accumulation in
      adipose tissue. The key role of APOA5 in TG metabolism has been largely shown
      through genetic studies in association with either severe or moderate
      hypertriglyceridemia. Studies suggest that APOA5 variants affect not only total
      TG concentrations but also the entire lipoprotein subclass distribution, shifting
      them toward atherogenic dyslipidemia in high-risk subjects. Environmental
      interactions and epigenetic factors are also crucial in regulating these
      processes. Delineation of the mechanisms involved in the transcriptional control
      of the gene, combined with determination of biological significance of the SNPs
      in the APOA5 locus, would help to fully understand the effect of APOA5 on TGs. In
      summary, APOA5 variants cause hypertriglyceridemia. In high cardiovascular risk
      patients (e.g., patients with metabolic syndrome or type 2 diabetes), APOA5
      variants elevate TG levels and shift the entire lipoprotein subclass distribution
      toward atherogenic dyslipidemia. At a physiological level, apoAV seems to
      encompass more roles than those initially suggested after its discovery.

PMID- 28500478
TI  - Effect of stenosis eccentricity on the functionality of coronary bifurcation
      lesions-a numerical study.
AB  - Interventional cardiologists still rely heavily on angiography for the evaluation
      of coronary lesion severity, despite its poor correlation with the presence of
      ischemia. In order to improve the accuracy of the current diagnostic procedures,
      an understanding of the relative influence of geometric characteristics on the
      induction of ischemia is required. This idea is especially important for coronary
      bifurcation lesions (CBLs), whose treatment is complex and is associated with
      high rates of peri- and post-procedural clinical events. Overall, it is unclear
      which geometric and morphological parameters of CBLs influence the onset of
      ischemia. More specifically, the effect of stenosis eccentricity is unknown.
      Computational fluid dynamic simulations, under a geometric multiscale framework,
      were executed for seven CBL configurations within the left main coronary artery
      bifurcation. Both concentric and eccentric stenosis profiles of mild to severe
      constriction were considered. By using a geometric multiscale framework, the
      fractional flow reserve, which is the gold-standard clinical diagnostic index,
      could be calculated and was compared between the eccentric and concentric
      profiles for each case. The results suggested that for configurations where the
      supplying vessel is stenosed, eccentricity could have a notable effect on and
      therefore be an important factor that influences configuration functionality.

PMID- 28500479
TI  - [Catheter ablation of persistent atrial fibrillation : Where do we go?]
AB  - Despite the very promising initial results of clinical studies, catheter ablation
      of persistent atrial fibrillation (AF) remains a challenge in modern
      electrophysiology. On the basis of the hypothesized pathophysiological
      mechanisms, a variety of ablation strategies have been developed over the course
      of time. The current ablation strategies range from pulmonary vein isolation
      (PVI) alone as first-line therapy, through ablation of multiple linear lesions,
      ablation of complex fractionated atrial electrograms (CFAE), rotor ablation,
      isolation of fibrotic and scar tissue up to isolation of the left atrial
      appendage (LAA); however, it is unclear even to the present day whether these
      complex and time-consuming strategies actually improve the success rate of
      ablation therapy. In recent years it has reproducibly been shown that with these
      ablation techniques more than one procedure is often necessary in order to
      achieve a stable sinus rhythm and even then only limited satisfactory success
      rates can be expected. The only currently established ablation endpoint is PVI.
      The stringent treatment of risk factors, such as arterial hypertension and
      obesity is becoming a focus of interest as an additive concept to ablation.

PMID- 28500480
TI  - [Pulmonary vein isolation for atrial fibrillation : Findings from long-term
      follow-up].
AB  - Atrial fibrillation is by far the most common cardiac arrhythmia in humans. The
      incidence of atrial fibrillation increases with age and will increase even more
      in the future due to the demographic changes in the population. Therefore, this
      arrhythmia will have a growing clinical and socioeconomic impact. Although there
      are established pharmaceutical treatment options, atrial fibrillation is one of
      the major causes of stroke, heart failure and cardiovascular morbidity and
      mortality. The latest guidelines recommend the invasive procedure of
      circumferential pulmonary vein isolation (PVI) as an effective treatment of
      paroxysmal and persistent atrial fibrillation. This article summarizes the
      current long-term follow-up data after PVI.

PMID- 28500482
TI  - Improved Yield of High Molecular Weight Hyaluronic Acid Production in a Stable
      Strain of Streptococcus zooepidemicus via the Elimination of the Hyaluronidase
      Encoding Gene.
AB  - Despite the significant potential of Streptococcus zooepidemicus for hyaluronic
      acid (HA) production with high molecular weight (MW), the HA degrading properties
      of hyaluronidase prevents the bacteria to achieve enhanced HA yield with high MW.
      In the present study, we aim to knockout the hyaluronidase enzyme and assess its
      effects on the yield and MW of the produced HA. The kanamycin resistance gene
      between the left and right arms of hyaluronidase gene was inserted into pUC18
      plasmid to construct pUC18-L-kanar-R as a recombinant suicide plasmid. The
      construct was then transferred into S. zooepidemicus to induce the homologous
      recombination between the hyaluronidase gene and the kanamycin resistance gene.
      Gene deletion was confirmed by PCR and enzyme assay. The product was cultured on
      selectable medium in which the MW of HA was increased from 1.5 to 3.8 MDa. The
      yield of HA production using the mutant strain was higher in all different
      concentrations of glucose from 40 to 120 g/l. Moreover, glucose increase results
      in higher HA production within both wild-type and recombinant strains. However,
      the growth rate of HA concentration (the slope of the plot), as a consequence of
      increased glucose concentration, is always higher for the recombinant strain.
      Unlike the wild-type strain, there was no sharp HA production drop approaching
      the 6 g/l HA concentration. In conclusion, hyaluronidase activity and HA
      concentration and MW exhibited a mutual control on each other. Based on our
      results, deletion of the hyaluronidase gene positively affects the yield and MW
      of HA.

PMID- 28500483
TI  - The effect of repetitive flexion and extension fatigue loading on the young
      porcine lumbar spine, a feasibility study of MRI and histological analyses.
AB  - BACKGROUND: The biomechanical mechanisms of failure of FSUs have been studied but
      the correlation of repetitive flexion and extension loadings to the initial phase
      of fatigue in young FSUs are still not known. The purpose of the study was to
      examine the fatigue results of low magnitude repetitive flexion and extension
      loading on porcine lumbar Functional Spinal Units (FSUs) with Magnetic Resonance
      Imaging (MRI) and histology. METHODS: Eight FSUs were subject to repetitive pivot
      flexion and eight to extension loading by a protocol of 20 000 cycles at 1 Hz
      with a load of 700 N. All loaded FSUs (N = 16) were examined with MRI and
      histology post loading. Three FSUs were examined with MRI as controls. Further
      three FSUs were non loaded histology controls. RESULTS: Fifteen (94%) of the
      loaded FSUs have decreased MRI signal in the growth zone of the superior vertebra
      and 12 (75%) in the inferior vertebrae. Fourteen (88%) FSUs have increased signal
      in the superior vertebral body. Fourteen (88%) FSUs have a reduced signal in all
      or any endplate. The histology morphometry displayed that the unstained parts of
      the epiphyseal growth zone were larger among the loaded FSUs (mean 29% vs 4%) and
      that the chondrocytes in the endplate and growth zones had abnormal structure and
      deformed extracellular matrix. CONCLUSION: Repetitive loading of young porcine
      FSUs in both extension and flexion causes concurrent MRI and histological changes
      in the growth zones and endplates, which could be a first sign of fatigue and an
      explanation for the disc, apophyseal and growth zone injuries seen among
      adolescent athletes.

PMID- 28500481
TI  - Pathways Linking Adverse Childhood Experiences to Cigarette Smoking Among Young
      Black Men: a Prospective Analysis of the Role of Sleep Problems and Delayed
      Reward Discounting.
AB  - BACKGROUND: African American men experience increases in smoking during the young
      adult transition. Exposure to childhood adversity, a risk factor which
      disproportionately affects African American men, has been identified as a robust
      precursor to health risk behavior in general and cigarette smoking in particular.
      The intermediate mechanisms that transmit the influence of early adversity to
      smoking behavior are not well understood. PURPOSE: We tested a model of the
      escalation of smoking behaviors among young adult African American men,
      investigating sleep disturbance and delayed reward discounting as intermediate
      factors linking adverse childhood experiences with smoking. METHODS: Hypotheses
      were tested with three waves of data (M age-T1 = 20.34, M age-T2 = 21.92, M age
      T3 = 23.02) from 505 African American men living in rural counties in South
      Georgia. Men provided self-report data on their adverse childhood experiences,
      sleep problems, and smoking behavior using audio-assisted computer self
      interviews. Men also completed a computer-based delayed reward discounting task.
      RESULTS: Structural equation modeling analyses supported our hypotheses: Adverse
      childhood experiences predicted poor sleep adequacy, which forecast increases in
      delayed reward discounting; discounting, in turn, predicted increased smoking.
      Significant indirect pathways were detected linking adversity to discounting via
      sleep adequacy and linking sleep adequacy to smoking via discounting.
      CONCLUSIONS: Prevention and intervention researchers can draw on these findings
      to develop programs that focus on sleep adequacy to reduce smoking in African
      American men exposed to childhood adversity.

PMID- 28500484
TI  - Association of folate metabolism gene polymorphisms and haplotype combination
      with pulmonary embolism risk in Chinese Han population.
AB  - In this study, we aimed to investigate the association of four single nucleotide
      polymorphisms (SNPs) (MTHFR 677 C > T, MTHFR 1298 A > C, MTR 2756 A > G and MTRR
      66 A > G), gene-gene interaction and haplotype combination with pulmonary
      embolism (PE) risk based on Chinese Han population. Logistic regression was
      performed to investigate association between four SNPs within folate metabolism
      gene and PE risk, and GMDR model was used to investigate the additional gene-gene
      interactions among the four SNPs. Logistic analysis showed that rs1801133 and
      rs1801131 in MTHFR gene were associated with increased PE risk in both additive
      and dominant models. The carriers with homozygous mutant of rs1801133
      polymorphism and homozygous of rs1801131 were associated with increased PE risk,
      and ORs (95% CI) were 1.71(1.24-2.21) and 1.58 (1.24-2.01), respectively. We also
      found a significant gene-gene interaction between rs1801133 and rs1801131 on PE.
      Overall, the cross-validation consistency of this two-locus model was 10/10, and
      the testing accuracy was 60.72%, after adjusting for covariates. Haplotype
      containing the rs1801133- T and rs1801131- C alleles were associated with a
      statistically increased PE risk, OR (95% CI) = 2.68 (1.28-4.13), P < 0.001. We
      found that rs1801133 and rs1801131 within MTHFR gene, their interaction, and
      haplotype containing the rs1801133- T and rs1801131- C alleles were all
      associated with PE risk.

PMID- 28500485
TI  - Hydroxyurea-Lactose Interaction Study: In Silico and In Vitro Evaluation.
AB  - The Maillard reaction between hydroxyurea (a primary amine-containing drug) and
      lactose (used as an excipient) was explored. The adduct of these compounds was
      synthesized by heating hydroxyurea with lactose monohydrate at 60  degrees C in
      borate buffer (pH 9.2) for 12 h. Synthesis of the adduct was confirmed using UV
      visible spectroscopy and Fourier transform infrared, differential scanning
      calorimetry, high-pressure liquid chromatography, and liquid chromatography-mass
      spectrometry studies. An in silico investigation of how the adduct formation
      affected the interactions of hydroxyurea with its biological target
      oxyhemoglobin, to which it binds to generate nitric oxide and regulates fetal
      hemoglobin synthesis, was carried out. The in silico evaluations were
      complemented by an in vitro assay of the anti-sickling activity. Co-incubation of
      hydroxyurea with deoxygenated blood samples reduced the percentage of sickled
      cells from 38% to 12 +/- 1.6%, whereas the percentage of sickled cells in samples
      treated with the adduct was 17 +/- 1.2%. This indicated loss of anti-sickling
      activity in the case of the adduct. This study confirmed that hydroxyurea can
      participate in a Maillard reaction if lactose is used as a diluent. Although an
      extended study at environmentally feasible temperatures was not carried out in
      the present investigation, the partial loss of the anti-sickling activity of
      hydroxyurea was investigated along with the in silico drug-target interactions.
      The results indicated that the use of lactose in hydroxyurea formulations needs
      urgent reconsideration and that lactose must be replaced by other diluents that
      do not form Maillard adducts.

PMID- 28500486
TI  - Tips and tricks for a safe and effective image-guided percutaneous renal tumour
      ablation.
AB  - : Image-guide thermal ablations are nowadays increasingly used to provide a
      minimally invasive treatment to patients with renal tumours, with reported good
      clinical results and low complications rate. Different ablative techniques can be
      applied, each with some advantages and disadvantages according to the clinical
      situation. Moreover, percutaneous ablation of renal tumours might be complex in
      cases where there is limited access for image guidance or a close proximity to
      critical structures, which can be unintentionally injured during treatment. In
      the present paper we offer an overview of the most commonly used ablative
      techniques and of the most important manoeuvres that can be applied to enhance
      the safety and effectiveness of percutaneous image-guided renal ablation.
      Emphasis is given to the different technical aspects of cryoablation,
      radiofrequency ablation, and microwave ablation, on the ideal operating room
      setting, optimal image guidance, application of fusion imaging and virtual
      navigation, and contrast enhanced ultrasound in the guidance and monitoring of
      the procedure. Moreover, a series of protective manoeuvre that can be used to
      avoid damage to surrounding sensitive structures is presented. A selection of
      cases of image-guided thermal ablation of renal tumours in which the discussed
      technique were used is presented and illustrated. TEACHING POINTS: *
      Cryoablation, radiofrequency and microwave ablation have different advantages and
      disadvantages. * US, CT, fusion imaging, and CEUS increase an effective image
      guidance. * Different patient positioning and external compression may increase
      procedure feasibility. * Hydrodissection and gas insufflation are useful to
      displace surrounding critical structures. * Cold pyeloperfusion can reduce the
      thermal damage to the collecting system.

PMID- 28500487
TI  - High-frame rate vector flow imaging of the carotid bifurcation.
AB  - : Carotid artery atherosclerotic disease is still a significant cause of
      cerebrovascular morbidity and mortality. A new angle-independent technique,
      measuring and visualizing blood flow velocities in all directions, called vector
      flow imaging (VFI) is becoming available from several vendors. VFI can provide
      more intuitive and quantitative imaging of vortex formation, which is not clearly
      distinguishable in the color Doppler image. VFI, as quantitative method assessing
      disturbed flow patterns of the carotid bifurcation, has the potential to allow
      better understanding of the diagnostic value of complex flow and to enhance risk
      stratification. This pictorial review article will show which new information VFI
      adds for the knowledge of hemodynamics in comparison to the conventional
      ultrasound techniques. TEACHING POINTS: * VFI is an angle-independent technique
      measuring flow velocities in all directions. * This kind of VFI is based on a
      plane wave multidirectional excitation technique. * VFI allows quantitative
      assessment of carotid streamlines progression and visualizes vorticity. * VFI
      does not allow a precise comprehension of streamlines' 3D shape. * VFI allows a
      better understanding of carotid artery complex flows.

PMID- 28500488
TI  - [Analysis of intrusion errors in free recall].
AB  - Extra-list intrusion errors during five trials of the eight-word list-learning
      task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823
      consecutive psychogeriatric patients (87.1% suffering from major neurocognitive
      disorder). Almost half of the participants (45.9%) produced one or more intrusion
      errors on the verbal recall test. Correct responses were lower when subjects made
      intrusion errors, but learning slopes did not differ between subjects who
      committed intrusion errors and those who did not so. Bivariate regression
      analyses revealed that participants who committed intrusion errors were more
      deficient on measures of eight-word recognition memory, delayed visual
      recognition and tests of executive control (the Behavioral Dyscontrol Scale and
      the ADST-Graphical Sequences as measures of response inhibition). Using
      hierarchical multiple regression, only free recall and delayed visual recognition
      retained an independent effect in the association with intrusion errors, such
      that deficient scores on tests of episodic memory were sufficient to explain the
      occurrence of intrusion errors. Measures of inhibitory control did not add
      significantly to the explanation of intrusion errors in free recall, which makes
      insufficient strength of memory traces rather than a primary deficit in
      inhibition the preferred account for intrusion errors in free recall.

PMID- 28500489
TI  - Population-based study of grade progression in patients who harboured Gleason 3 +
      3.
AB  - PURPOSE: This study aimed to evaluate (1) the time interval between a decision to
      commence on active surveillance (AS) and grade progression in community practice;
      (2) factors predicting grade progression in localised prostate cancer (CaP)
      patients apparently undergoing AS. METHODS: Data from the Prostate Cancer
      Outcomes Registry-Victoria were used to analyze men with Gleason 3 + 3 CaP or
      less who had at least one repeat biopsy. Unadjusted and adjusted 5-year Kaplan
      Meier survival curves were used to assess the time to grade progression. Both
      univariate and multivariate analyses for grade progression were performed using
      Cox proportional hazards. RESULTS: The cohort included 951 men. Overall, 39% of
      men had Gleason grade reclassified to a higher risk disease state with median of
      2.2 years [IQR 1.2-3.7 years]. Men who harboured cT2 disease were 30% more likely
      to have upgrading compared to men with cT1 disease (adjusted HR: 1.3, 95% CI 1.0
      1.6, p = 0.048). Half of the men with cT2 in our cohort had their Gleason grade
      reclassified within 1.6 years from diagnosis as compared with 2.7 years for the
      cT1 group. The presence of percentage of core involvement >25.0% and a PSA
      velocity of >1.01 ng/mL/year remained significant for a higher progression rate.
      The adjusted HR: 1.6; 95% CI [1.2-2.3], p = 0.004; adjusted HR: 1.6, 95% CI [1.2
      2.4], p = 0.021, for percent of core involvement of 25.1-37.5%, and >=37.6%,
      respectively. The adjusted HRs and p value associated with PSA velocity were 1.5;
      95% CI [1.1-2.1], p = 0.016 and 1.6; 95% CI [1.2-2.3], p = 0.003 for PSA velocity
      values of 1.01-2 ng/mL per year and >2 ng/mL per year, respectively. Men who were
      diagnosed in regional hospital and subsequently had biopsy in metropolitan
      hospital were twice at risk of having Gleason upgrade compared to those whom both
      diagnostic and surveillance biopsies were carried out in metropolitan hospitals
      (adjusted HR: 1.9; 95% CI 1.1-3.3, p = 0.029). CONCLUSIONS: When placing men on
      AS and considering time to histologic progression, clinicians should pay
      particular attention to the likely accuracy of the diagnostic specimen, their
      tumour stage, volume of tumour (percent of core involvement), and rising PSA.
      Those diagnosed with T2 disease and had >25.0% of core involvement, and a PSA
      velocity greater than 1 ng/mL per year is at particular risk for more rapid
      disease progression and, for this reason, should be counselled on the importance
      of following the recommended surveillance regimen. For half of these men, their
      disease will have 'progressed' according to biopsy results in 2 years.

PMID- 28500490
TI  - Effects of definitive and salvage radiotherapy on the distribution of lymphocyte
      subpopulations in prostate cancer patients.
AB  - BACKGROUND: Radiotherapy (RT) is an established treatment for patients with
      primary and recurrent prostate cancer. Herein, the effects of definitive and
      salvage RT on the composition of lymphocyte subpopulations were investigated in
      patients with prostate cancer to study potential immune effects. PATIENTS AND
      METHODS: A total of 33 prostate cancer patients were treated with definitive (n =
      10) or salvage RT (n = 23) after biochemical relapse. The absolute number of
      lymphocytes and the distribution of lymphocyte subpopulations were analyzed by
      multiparameter flow cytometry before RT, at the end of RT, and in the follow-up
      period. RESULTS: Absolute lymphocyte counts decreased significantly after RT in
      both patient groups and a significant drop was observed in the percentage of B
      cells directly after RT from 10.1 +/- 1.3 to 6.0 +/- 0.7% in patients with
      definitive RT and from 9.2 +/- 0.8 to 5.8 +/- 0.7% in patients with salvage RT.
      In contrast, the percentages of T and natural killer (NK) cells remained
      unaltered directly after RT in both patient groups. However, 1 year after RT, the
      percentage of CD3+ T cells was significantly lower in patients with definitive
      and salvage RT. The percentage of regulatory T cells was slightly upregulated in
      primary prostate cancer patients after definitive RT, but not after salvage RT.
      CONCLUSION: Definitive and salvage RT exert similar effects on the composition of
      lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts
      are lower in both patient groups compared to healthy controls and further
      decreased after RT. B cells are more sensitive to definitive and salvage RT than
      T and NK cells.

PMID- 28500491
TI  - Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin
      chemotherapy in locally advanced inoperable squamous cell carcinoma of the head
      and neck : Final 5-year results of a phase II study.
AB  - BACKGROUND: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor
      receptor and has been shown to have activity in squamous cell carcinoma of the
      head and neck (SCCHN). We conducted a single-arm phase II trial of a combination
      therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated
      radiotherapy (HART). PATIENTS AND METHODS: Patients with UICC stage III or IVA/B,
      M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m2) and
      then with a weekly dosage of 250 mg/m2 during HART. HART was started with a
      prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily
      to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m2) was
      administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the
      phase II study was to determine the 2-year progression-free survival (PFS).
      RESULTS: Between November 2007 and November 2010, a total of 74 patients were
      enrolled in the study, of whom 65 were evaluable (83% were men). Median age was
      56 years (range 37-69 years). An Oropharyngeal primary tumour was diagnosed in
      49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were
      smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%).
      The most common toxicity grade was >=3, including mucositis (58%) and dysphagia
      (52%). The 2- and 5-year overall survival rates were 64 and 41%, the 2- and 5
      year PFS rates were 45 and 32%, and the 2- and 5-year locoregional control rates
      were 47 and 33%, respectively. CONCLUSION: The combination of weekly CIS with
      HART plus CET is a feasible regimen for these unfavourable smoking-induced
      cancers. However, the parallel US study (RTOG 0522) showed no advantage of the
      enhanced triple therapy compared to chemoradiotherapy alone.

PMID- 28500493
TI  - Impaired XPO5 function leads to transportation failure of microRNA precursor.

PMID- 28500492
TI  - Treatment of withdrawal headache in patients with medication overuse headache: a
      pilot study.
AB  - BACKGROUND: Drug withdrawal still remains the key element in the treatment of
      Medication Overuse Headache (MOH), but there is no consensus about the withdrawal
      procedure. Still debated is the role of the steroid therapy. The aim of this
      study was to evaluate the effectiveness of methylprednisolone or paracetamol in
      the treatment of withdrawal headache in MOH. METHODS: We performed a pilot,
      randomized, single-blinded, placebo controlled trial. MOH patients, unresponsive
      to a 3 months prophylaxis, underwent withdrawal therapy on an inpatient basis.
      Overused medications were abruptly stopped and methylprednisolone 500 mg i.v (A)
      or paracetamol 4 g i.v. (B) or placebo i.v. (C) were given daily for 5 days.
      Patients were monitored at 1 and 3 months. RESULTS: Eighty three consecutive MOH
      patients were enrolled. Fifty seven patients completed the study protocol.
      Nineteen patients were randomized to each group. Withdrawal headache on the 5th
      day was absent in 21.0% of group A, in 31.6% of group B and in 12.5% of group C
      without significant differences. Withdrawal headache intensity decreased
      significantly after withdrawal without differences among the groups. Rregardless
      of withdrawal treatment, 52% MOH patients reverted to an episodic migraine and
      62% had no more medication overuse after 3 months. CONCLUSIONS: This study
      suggests that in a population of severe MOH patients, withdrawal headache
      decreased significantly in the first 5 days of withdrawal regardless of the
      treatment used. Methylprednisolone and paracetamol are not superior to placebo at
      the end of the detoxification program.

PMID- 28500494
TI  - Three divergent approaches identified the same RGF1 receptors in Arabidopsis
      thaliana.

PMID- 28500495
TI  - Causes for early and late surgical re-intervention after radial head
      arthroplasty.
AB  - PURPOSE: The primary objective was to describe the reasons for surgical re
      intervention after radial head arthroplasty. The secondary objective was to
      analyze the radiographic and clinical outcomes after surgical re-intervention at
      the elbow with implant conservation. METHODS: Among the 70 radial head
      arthroplasties with bipolar radial head implant performed between 2002 and 2014,
      29 required surgical re-interventions. Reasons for surgical re-intervention were
      gathered from operative notes and follow-up documentation. Patients who underwent
      re-intervention with implant retention were reassessed via clinical and
      radiographic examinations by an independent reviewer. RESULTS: Twenty nine re
      operations were performed at a mean follow-up of 16 +/- 11.7 months (0.2-36
      months). The prosthesis was removed in 18 cases and retained in 11. There was a
      significant difference in mean time to re-intervention between the implant
      removal and preservation groups, 23.1 +/- 8.3 months (7-36 months) and 4.4 +/-
      4.7 months (0.2-13 months), respectively (p < 0.001). The primary reason for
      surgical re-intervention was painful loosening (13 cases). Radio-capitellar
      instability was the most frequent reason for re-intervention with implant
      retention (5 cases). Midterm quickDASH and MEPS after surgical re-intervention
      with implant retention were 15.4 +/- 5.4 and 82.27 +/- 7.3, respectively. At
      least one degenerative lesion was reported in nine cases (81.8%) (i.e. 5
      periprosthetic osteolysis, 5 capitellar wear, 5 periarticular heterotopic
      ossification). CONCLUSIONS: Painful loosening and capitellar instability are the
      primary reasons for surgical re-intervention with or without implant removal.
      Midterm clinical results are favourable despite an elevated rate of degenerative
      lesions after surgical re-intervention with implant retention.

PMID- 28500496
TI  - Patient-specific instrumentation improves alignment of lateral unicompartmental
      knee replacements by novice surgeons.
AB  - PURPOSE: Patient-specific instrumentation (PSI) has the potential to offer
      numerous benefits-not least of all, improved resection accuracy; but its
      potential has not been realised in clinical studies. An explanation may be the
      focus of such studies on the total knee replacement (TKR-a common procedure, with
      which surgeons are generally very familiar. Consequently, we sought to
      investigate the potential role of PSI in guiding novice surgeons to perform the
      more technically demanding and less familiar lateral unicondylar knee replacement
      (LUKR). METHODS: Twelve orthopaedic trainees naive to LUKR were instructed to
      perform the procedure according to a pre-operative plan. These were carried out
      on synthetic sawbones and were completed once with conventional instrumentation
      alone and once with the adjunct of PSI, allowing a comparison of the plan
      adherence achieved by the two sets of instrumentation. RESULTS: There was a
      tendency for PSI to demonstrate improved plan adherence, though a statistically
      significant improvement was only seen in compound rotational error of the femoral
      implant (p = 0.004). PSI was, however, able to produce narrower standard
      deviations in the mean translational displacement of the femoral implant and also
      the mean rotational displacement of both implants, suggesting a higher degree of
      precision. CONCLUSIONS: Our study provides some evidence that PSI can improve the
      ability of novice surgeons to replicate a pre-operative plan, but our results
      suggest the need for larger-scale clinical studies to establish the role of PSI
      in this procedure.

PMID- 28500498
TI  - [Aging, technical aids, and the socio-gerontological dialog-the IDA
      interdisciplinary guide].

PMID- 28500497
TI  - Evaluation of endothelialization in the center part of graft using 3 cm vascular
      grafts implanted in the abdominal aortae of the rat.
AB  - In order to develop small-diameter vascular grafts, it is necessary to evaluate
      endothelialization, especially, in the center part at early stage. For
      implantation of vascular grafts of 1 cm in length to abdominal aortae of rat,
      endothelial cells can be formed easily by stretching anastomosis. We evaluated
      the endothelialization in the center part of vascular grafts by implanting
      vascular grafts using transgenic (TG) silk fibroin (SF) of 3 cm in length.
      Vascular grafts were prepared 1.5 mm in diameter and 1 and 3 cm in length using
      wild type (WT) SF and TG SF by braiding structure, respectively. The grafts were
      removed after 2 weeks or 3 months and evaluated pathologically.
      Endothelialization was not confirmed totally after 3 months of implantation.
      However, endothelialization in the center part of grafts was significantly higher
      in TG SF than in WT SF. No significant difference was found regarding tissue
      infiltration and internal diameter. The TG SF revealed migration of the
      endothelial cells into the center part of the vessels at the early stage. Also,
      tissue infiltration and remodeling is expected using SF. The 3 cm length vascular
      grafts can be evaluated as a new experimental system.

PMID- 28500499
TI  - [Anesthesiological care of trauma patients in orthogeriatric co-management].
AB  - Elderly patients increasingly need to undergo surgery under anesthesia,
      especially following trauma. A timely interdisciplinary approach to the
      perioperative management of these patients is decisive for the long-term outcome.
      Orthogeriatric co-management, which includes geriatricians and anesthesiologists
      from an early stage, is of great benefit for geriatric patients. Patient age,
      comorbidities and self-sufficiency in activities of daily life are decisive for
      an anesthesiological assessment of the state of health and preoperative risk
      stratification. If necessary additional investigations, such as echocardiography
      must be carried out, in order to guarantee optimal perioperative
      anesthesiological management. Certain medical factors can delay the initiation of
      anesthesia and it is absolutely necessary that these are taken into consideration
      for surgical management. Not every form of anesthesia is equally suitable for
      every geriatric patient.

PMID- 28500500
TI  - [Epistemology in the intensive care unit-what is the purpose of a definition? :
      Paradigm shift in sepsis research].
AB  - The adoption of the new sepsis definition in early 2016 introduced a new paradigm
      for the clinical picture of sepsis. Up until now, sepsis was defined as a
      systemic inflammatory reaction (systemic inflammatory response syndrome, SIRS) to
      an infection. Based on a better understanding of the molecular mechanisms, the
      focus of the new definition is no longer the inflammatory response, but rather
      the tissue damage and impairment of organ function which this induces. The
      paradigm thus moves away from the infection and the systemic inflammatory
      response, and toward that which makes sepsis so dangerous in terms of both
      disease dynamics and outcome: organ failure due to a dysregulated host response
      to an infection. This change of perspective or paradigm enables patients with an
      increased risk of developing sepsis to be recognized and treated earlier in
      clinical routine, even outside of the intensive care unit. The new definition
      also promotes development of new treatment strategies with improved ability to
      treat sepsis causally.

PMID- 28500501
TI  - "Can One Put Faith and Work in the Same Sentence?" Faith Development and Vocation
      of a Female Leader in the Engineering Profession.
AB  - Faith has been pointed out as a possible resource in strengthening individuals'
      health and well-being at work. The aim of this article is to gain in-depth
      knowledge of the faith development and vocation of a selected female leader in a
      male-dominated work context. The article contributes to research on faith
      development in women leaders, based on Fowler's faith development theory. This is
      a single case study grounded in a qualitative research design. In-depth
      qualitative data were gathered through observation and interviews over 18 months.
      Findings showed the development of faith across a women leader's life span and
      highlight that faith and vocation are important resources that provide strength,
      meaningfulness and a vision.

PMID- 28500502
TI  - Retinoic acid regulates cell-shape and -death of E-FABP (FABP5)-immunoreactive
      septoclasts in the growth plate cartilage of mice.
AB  - Septoclasts, which are mononuclear and spindle-shaped cells with many processes,
      have been considered to resorb the transverse septa of the growth plate (GP)
      cartilage at the chondro-osseous junction (COJ). We previously reported the
      expression of epidermal-type fatty acid-binding protein (E-FABP, FABP5) and
      localization of peroxisome proliferator-activated receptor (PPAR)beta/delta,
      which mediates the cell survival or proliferation, in septoclasts. On the other
      hand, retinoic acid (RA) can bind to E-FABP and is stored abundantly in the GP
      cartilage. From these information, it is possible to hypothesize that RA in the
      GP is incorporated into septoclasts during the cartilage resorption and regulates
      the growth and/or death of septoclasts. To clarify the mechanism of the cartilage
      resorption induced by RA, we administered an overdose of RA or its precursor
      vitamin A (VA)-deficient diet to young mice. In mice of both RA excess and VA
      deficiency, septoclasts decreased in the number and cell size in association with
      shorter and lesser processes than those in normal mice, suggesting a substantial
      suppression of resorption by septoclasts in the GP cartilage. Lack of
      PPARbeta/delta-expression, TUNEL reaction, RA receptor (RAR)beta, and cellular
      retinoic acid-binding protein (CRABP)-II were induced in E-FABP-positive
      septoclasts under RA excess, suggesting the growth arrest/cell-death of
      septoclasts, whereas cartilage-derived retinoic acid-sensitive protein (CD-RAP)
      inducing the cell growth arrest or morphological changes was induced in
      septoclasts under VA deficiency. These results support and do not conflict with
      our hypothesis, suggesting that endogenous RA in the GP is possibly incorporated
      in septoclasts and utilized to regulate the activity of septoclasts resorbing the
      GP cartilage.

PMID- 28500504
TI  - Delay discounting and parental monitoring in adolescents with poorly controlled
      type 1 diabetes.
AB  - In a sample of adolescents with poorly controlled type 1 diabetes, this study
      examined if delay discounting, the extent to which individuals prefer immediate
      over delayed rewards, was associated with severity of non-adherence and poor
      glycemic control, and if parental monitoring of diabetes management moderated
      those associations. Sixty-one adolescents (M age = 15.08 years, SD 1.43) with
      poorly controlled type 1 diabetes completed a delayed discounting task and an
      HbA1c blood test. Adherence was assessed via self-monitoring of blood glucose
      (SMBG) data from adolescents' glucometers. Parents completed a parental
      monitoring questionnaire. Greater delay discounting was associated with higher
      HbA1c, but not SMBG. Direct parent observation of diabetes tasks, but not
      indirect parental monitoring, moderated the link between greater delay
      discounting and higher HbA1c, with higher direct parent observation buffering the
      link between greater discounting and poorer glycemic control. Delay discounting
      may be a target for future interventions to improve HbA1c in youth with type 1
      diabetes.

PMID- 28500505
TI  - Rehydration improves the ductility of dry bone allografts.
AB  - Processing of bone allografts improves infectious safety and allows storing bone
      substitutes at room temperature. The aim of this study was to compare mechanical
      properties of the processed OsteopureTM bone with fresh frozen bone. All the
      samples were pieces from femoral heads retrieved during hip arthroplasty
      operations. The processing includes chemical decellularization, drying and
      irradiation with 25 kGy. Three types of samples were tested: 1. fresh frozen
      thawed wet, 2. dry non-rehydrated graft 3. dry rehydrated graft. In the 3-point
      bending test Young's modulus and stress at break yielded no significant
      difference among the 3 different sample groups. Rehydrating of the dry graft
      showed increased ductility in strain at break test compared with the other 2
      groups (p = 0.003). In compression tests dry grafts had significantly higher
      maximum effective stress and apparent maximum deformation compared with the
      grafts of other groups (p < 0.05). Processed bone has almost similar mechanical
      properties compared with fresh frozen bone. However, rehydration of processed dry
      graft increases its ductility. These grafts may tolerate bending forces better
      before breakage.

PMID- 28500503
TI  - Expression and localization of myosin VI in developing mouse spermatids.
AB  - Myosin VI (MVI) is a versatile actin-based motor protein that has been implicated
      in a variety of different cellular processes, including endo- and exocytic
      vesicle trafficking, Golgi morphology, and actin structure stabilization. A role
      for MVI in crucial actin-based processes involved in sperm maturation was
      demonstrated in Drosophila. Because of the prominence and importance of actin
      structures in mammalian spermiogenesis, we investigated whether MVI was
      associated with actin-mediated maturation events in mammals. Both
      immunofluorescence and ultrastructural analyses using immunogold labeling showed
      that MVI was strongly linked with key structures involved in sperm development
      and maturation. During the early stage of spermiogenesis, MVI is associated with
      the Golgi and with coated and uncoated vesicles, which fuse to form the acrosome.
      Later, as the acrosome spreads to form a cap covering the sperm nucleus, MVI is
      localized to the acroplaxome, an actin-rich structure that anchors the acrosome
      to the nucleus. Finally, during the elongation/maturation phase, MVI is
      associated with the actin-rich structures involved in nuclear shaping: the
      acroplaxome, manchette, and Sertoli cell actin hoops. Since this is the first
      report of MVI expression and localization during mouse spermiogenesis and MVI
      partners in developing sperm have not yet been identified, we discuss some
      probable roles for MVI in this process. During early stages, MVI is hypothesized
      to play a role in Golgi morphology and function as well as in actin dynamics
      regulation important for attachment of developing acrosome to the nuclear
      envelope. Next, the protein might also play anchoring roles to help generate
      forces needed for spermatid head elongation. Moreover, association of MVI with
      actin that accumulates in the Sertoli cell ectoplasmic specialization and other
      actin structures in surrounding cells suggests additional MVI functions in
      spermatid movement across the seminiferous epithelium and in sperm release.

PMID- 28500506
TI  - A controlled comparison of the BacT/ALERT(r) 3D and VIRTUOTM microbial detection
      systems.
AB  - The performance of the next-generation BacT/ALERT(r) VIRTUOTM Microbial Detection
      System (VIRTUOTM, bioMerieux Inc., Hazelwood, MO) was compared to the
      BacT/ALERT(r) 3D Microbial Detection System (3D, bioMerieux Inc., Durham, NC)
      using BacT/ALERT(r) FA Plus (FA Plus), BacT/ALERT(r) PF Plus (PF Plus),
      BacT/ALERT(r) FN Plus (FN Plus), BacT/ALERT(r) Standard Aerobic (SA), and
      BacT/ALERT(r) Standard Anaerobic (SN) blood culture bottles (bioMerieux Inc.,
      Durham, NC). A seeded limit of detection (LoD) study was performed for each
      bottle type in both systems. The LoD studies demonstrated that both systems were
      capable of detecting organisms at nearly identical levels [<10 colony-forming
      units (CFU) per bottle], with no significant difference. Following LoD
      determination, a seeded study was performed to compare the time to detection
      (TTD) between the systems using a panel of clinically relevant microorganisms
      inoculated at or near the LoD with 0, 4, or 10 mL of healthy human blood.
      VIRTUOTM exhibited a faster TTD by an average of 3.5 h, as well as demonstrated a
      significantly improved detection rate of 99.9% compared to 98.8% with 3D (p-value
      <0.05).

PMID- 28500508
TI  - The whereabouts of visual attention: Involuntary attentional bias toward the
      default gaze direction.
AB  - This study proposed and verified a new hypothesis on the relationship between
      gaze direction and visual attention: attentional bias by default gaze direction
      based on eye-head coordination. We conducted a target identification task in
      which visual stimuli appeared briefly to the left and right of a fixation cross.
      In Experiment 1, the direction of the participant's head (aligned with the body)
      was manipulated to the left, front, or right relative to a central fixation
      point. In Experiment 2, head direction was manipulated to the left, front, or
      right relative to the body direction. This manipulation was based on results
      showing that bias of eye position distribution was highly correlated with head
      direction. In both experiments, accuracy was greater when the target appeared at
      a position where the eyes would potentially be directed. Consequently, eye-head
      coordination influences visual attention. That is, attention can be automatically
      biased toward the location where the eyes tend to be directed.

PMID- 28500507
TI  - Impact of severe hematological abnormalities in the outcome of hospitalized
      patients with influenza virus infection.
AB  - Although hematological abnormalities have been described among patients with
      influenza virus infection, little is known about their impact on the outcome of
      the patients. The aim of this study was to assess the frequency and clinical
      impact of severe hematological abnormalities in patients with confirmed influenza
      virus infection. This was an observational retrospective study including all
      adult patients with diagnosis of influenza virus infection hospitalized from
      January to May 2016 in our institution. Influenza virus infection was diagnosed
      by means of rRT-PCR assay performed on respiratory samples. Poor outcome was
      defined as a composite endpoint in which at least one of the following criteria
      had to be fulfilled: (a) respiratory failure, (b) SOFA >=2, or (c) death. Two
      hundred thirty-nine patients were included. Applying the HLH-04 criteria for the
      diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin <=9 g/dl, platelets
      <100,000/MUl or neutrophils <1,000/MUl) were present in 51 patients (21%).
      Patients with hematological abnormalities showed higher SOFA scores, respiratory
      failure, septic shock and in-hospital mortality than the remaining patients. The
      composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the
      group without cytopenias (p=0.001). In a multivariate analysis, variables
      associated with the composite endpoint were: use of steroids prior to present
      admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological
      abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45;
      CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among
      hospitalized patients with influenza virus infection, and they are associated
      with a poorer outcome.

PMID- 28500509
TI  - Observations of termitarium geophagy by Rylands' bald-faced saki monkeys
      (Pithecia rylandsi) in Madre de Dios, Peru.
AB  - Geophagy, or soil consumption, has been documented in diverse animal taxa,
      including many primates. Physiological functions such as mineral supplementation,
      detoxification of secondary compounds, and antacid properties are possible causes
      for this behavior. We report on observations of geophagy at arboreal termitaria
      by free-ranging Pithecia rylandsi at La Estacion Biologica Los Amigos (EBLA) in
      Peru between 2008 and 2015. Characteristics of geophagy events, including saki
      monkey behavior at the termitaria, were recorded and geochemical analyses were
      conducted on consumed termitaria, nearby topsoils, and unvisited termitaria. We
      observed 76 feeding bouts at 26 different termitaria by two groups of P. rylandsi
      during 1125 observational hours (0.07 bouts/obs. h). Geophagy occurred throughout
      the year, but rates peaked in January during the rainy season. All age and sex
      classes visited both active and inactive mounds. Feeding bouts were brief (171 +/
      SD 154 s), and no differences were observed in time spent feeding at active or
      inactive termitaria. Analyses showed that consumed soils contained higher
      concentrations of phosphorous, potassium, calcium, and magnesium than did
      topsoil. Consumed soils also contained a higher total cation exchange capacity
      than topsoil. Our analysis of consumed versus control termitaria revealed no
      differences in their chemical composition. We discuss these results in the
      context of the two primary hypotheses proposed for geophagy in pitheciins:
      mineral supplementation and toxin adsorption. Our data are consistent with the
      interpretation that P. rylandsi consume soils from arboreal termitaria to aid in
      adsorption of toxins found in immature seeds, which are a year-round component of
      their diet.

PMID- 28500513
TI  - Erratum to: Surgeons' views on sling tensioning during surgery for female stress
      urinary incontinence.

PMID- 28500512
TI  - Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice.
AB  - Chronic stress is a risk factor for major depression. Social defeat stress is a
      well-validated murine model of depression. However, little is known about the
      gene activity dynamics during the development of a depression-like state. We
      analyzed the effects of social defeat stress of varying duration (10 and 30 days)
      on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice.
      The 10-day exposure to social defeat stress resulted in a high level of social
      avoidance with no signs of depression-associated behavior. Most animals exposed
      to 30 days of social defeat stress demonstrated clear hallmarks of depression,
      including a higher level of social avoidance, increased immobility in the forced
      swimming test, and anhedonic behavior. The monitoring of transcriptome changes
      revealed widespread alterations in gene expression on the 10th day. Surprisingly,
      the expression of only a few genes were affected by the 30th day of stress,
      apparently due to a reversal of the majority of the early stress-induced changes
      to the original basal state. Moreover, we have found that glucocorticoid
      sensitive genes are clearly stimulated targets on the 10th day of stress, but
      these genes stop responding to the elevated corticosterone level by the 30th day
      of stress. The majority of genes altered by the 30-day stress were downregulated,
      with the most relevant ones participating in chromatin modifications and
      neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of
      GTPases). Very different molecular responses occur during short-term and long
      term social stress in mice. The early-stress response is associated with social
      avoidance and with upregulation and downregulation of many genes, including those
      related to signal transduction and cell adhesion pathways. Downregulation of a
      few genes, in particular, genes for histone-modifying methyltransferases, is a
      signature response to prolonged stress that induces symptoms of depression.
      Altogether, our data show that the development of depression under social stress
      conditions is correlated with suppression of the overactive molecular response to
      induced stress, involving gene regulatory resistance to glucocorticoid molecules,
      potentially via a chromatin remodeling mechanism.

PMID- 28500515
TI  - Outpatient mid-urethral tissue fixation system sling for urodynamic stress
      urinary incontinence: 3-year surgical and quality of life results.
AB  - INTRODUCTION: To evaluate the clinical effectiveness and quality of life (QOL) of
      outpatient mid-urethral tissue fixation system sling (TFS) procedures for
      urodynamic stress urinary incontinence (SUI) at 3-year follow-up. METHODS: We
      analyzed 50 mid-urethral TFS sling operations between 2007 and 2012 at Yokohama
      Motomachi Women's Clinic LUNA. The primary outcome was success defined as a
      negative 24-h pad test, negative cough and Valsalva stress test, and no re
      treatment for SUI. Secondary outcome was improvement in quality of life, which
      was assessed using the Incontinence Questionnaire-Short Form (ICIQ-SF) and the
      Incontinence Impact Questionnaire Short Form (IIQ-7). The 3-year postoperative
      scores were compared with baseline scores using the Wilcoxon signed rank test. A
      5% two-sided significance level was used for all statistical testing. RESULTS:
      All operations were carried out on an outpatient basis with no intraoperative
      complications. The primary cure rate result at 3-year follow-up was 90%. Median
      total ICIQ-SF score changed from 12 (6-20) to 0 (0-14) and median total IIQ-7
      score changed from 156 (0-300) to 0 (0.00-16.7) at 3-year follow-up. CONCLUSIONS:
      Results show that the TFS mid-urethral sling operation is a simple, safe,
      effective procedure that may be done without difficulty at a freestanding clinic
      on an outpatient basis and favorably improves subjective QOL of the patient.

PMID- 28500516
TI  - Nd:YAG laser irradiation associated with fluoridated gels containing photo
      absorbers in the prevention of enamel erosion.
AB  - This study evaluated the combined effect of Nd:YAG laser irradiation and
      fluoridated gels containing photo absorbers against enamel erosion. Enamel
      specimens from bovine teeth were polished, eroded (10 min, with 1% citric acid,
      pH = 2.6), and randomly allocated into the experimental groups (n = 8), according
      to the different surface treatments: fluoridated gels (F: 9047 ppm F and F + Sn:
      9047 ppm F and 3000 ppm Sn), with or without photo absorbers (E: erythrosine and
      MB: methylene blue), and associated or not with Nd:YAG laser irradiation (in
      contact; 0.5 W; 50 mJ; ~41.66 J/cm2; 10 Hz; 40 s; pulse duration of 120 MUs). A
      placebo gel (PLA) associated or not with laser was used as control. All gels had
      pH = 4.5 and were applied for 2 min. Laser irradiation was performed during gel
      application. The specimens were then submitted to a 5-day erosion
      remineralization cycling model using 0.3% citric acid (pH = 2.6), 4*/day. Enamel
      surface loss (SL) was analyzed by optical profilometry in the end of the cycling
      (in MUm). Data were analyzed by ANOVA and Tukey tests (alpha = 0.05). Means (SD)
      of SL for the groups were the following (different superscript letters imply
      significant difference among groups): PLA (21.02 +/- 1.28)a, PLA + laser (19.20
      +/- 0.96)ab, laser (17.47 +/- 1.50)b, F + Sn + E + laser (13.69 +/- 0.62)c, F + E
      + laser (13.52 +/- 1.16)c, F (13.10 +/- 1.08)c, F + laser (11.94 +/- 1.44)cd, F +
      Sn + MB + laser (11.90 +/- 4.02)cd, F + MB + laser (11.42 +/- 1.42)cd, F + Sn
      (11.12 +/- 1.20)cd, and F + Sn + laser (10.35 +/- 0.89)d. In conclusion, all
      fluoridated gels and the Nd:YAG laser irradiation reduced erosion development,
      but the combination of treatments did not promote further protection. The
      addition of photo absorbers to the fluoridated gels did not influence the anti
      erosive effect of the combination of laser plus fluoridated gels.

PMID- 28500517
TI  - Role of Non-Statins, LDL-C Thresholds, and Special Population Considerations: A
      Look at the Updated 2016 ACC Consensus Committee Recommendations.
AB  - PURPOSE OF REVIEW: The 2013 ACC/AHA Cholesterol guidelines was a major paradigm
      shift in the management and treatment of dyslipidemia. The new guidelines
      outlined "statin benefit groups," highlighted weighing the benefit versus risks
      of statin therapy ("net benefit"), and discussed the importance of shared
      decision making between patients and providers in primary prevention. While there
      was widespread agreement on the main groups benefiting from statin therapy, there
      was significant controversy regarding LDL-C goals and thresholds, the role of non
      statin therapy, and the use of statins in specific populations. The goal of this
      review is to understand the rationale for the updated 2016 ACC Expert Consensus
      on Non-Statins and to contrast it with the 2015 NLA Recommendations on the
      Management of Dyslipidemia. RECENT FINDINGS: The findings of the ACC Expert
      Consensus Panel were largely influenced by the results of several new clinical
      trials using non-statin therapy in combination with moderate to high intensity
      statin therapy. The IMPROVE-IT trial demonstrated that ezetimibe on top of statin
      therapy lowered ASCVD risk in patients with acute coronary syndromes whose LDL
      was driven below the previous LDL-C target of <70 mg/dL. In addition, preliminary
      data assessing the safety of evolocumab and alirocumab on top of statin therapy
      suggested possible large reductions in ASCVD risk in post hoc analysis. Both the
      2016 ACC Consensus Recommendations and the 2015 NLA Recommendations emphasize the
      importance of maximally tolerated statin therapy, the use of adjunctive non
      statin LDL lowering therapy, and the use of LDL-C goals and thresholds to guide
      intensification of LDL lowering therapy. Although there are some important
      differences between the ACC Consensus and NLA recommendations in terms of
      treatment of special populations (i.e., CHF) and on the use of non-HDL-C goals
      and thresholds, both guidelines support a role for ezetimibe, bile acid
      sequestrants, and PCSK-9 inhibitors in patients on maximum tolerated statin
      therapy. The recent positive results of the FOURIER trial gives additional
      support to the non-statin recommendations of both the ACC and NLA.

PMID- 28500518
TI  - Incremental start to PD as experienced in Italy: results of censuses carried out
      from 2005 to 2014.
AB  - BACKGROUND: It is not known how widely used in Italy an incremental start to in
      peritoneal dialysis (Incr-PD) is. METHODS: By analyzing the peritoneal dialysis
      (PD) censuses conducted by the PD Study Group (GSDP-SIN) for the years 2005,
      2008, 2010, 2012 and 2014 in all the Centers performing PD in Italy, the use of
      Incr-PD, i.e. continuous ambulatory peritoneal dialysis (CAPD) with 1 or 2
      exchanges/day or automated peritoneal dialysis (APD) with 3-4 sessions/week, was
      examined among incident PD patients. RESULTS: In 2014 PD was started in Italy by
      1,652 patients, 455 (27.5%) of whom incrementally (Incr-CAPD 82.2% vs. Incr-APD
      17.8%). Incr-PD was used in 53.5% of the 225 Centers. The number of patients and
      of Centers using Incr-DP increased constantly over the years up to 2012 (in 2005
      Incr-PD was used in 33.4% of Centers, and in 11.9% of patients). The use of Incr
      PD was greater in Centers with a more extensive PD program and greater use of PD
      in general. The most widely-used modality in Incr-PD was CAPD. CONCLUSIONS: Incr
      PD is used in Italy in a large number of incident PD patients. The reasons for
      this increase need to be clarified, as current adequacy targets are based on full
      dose studies with a very low glomerular filtration rate (GFR).

PMID- 28500519
TI  - DFT study of CO2 and H2O co-adsorption on carbon models of coal surface.
AB  - The moisture content of coal affects the adsorption capacity of CO2 on the coal
      surface. Since the hydrogen bonds are formed between H2O and oxygen functional
      group, the H2O cluster more easily adsorbs on the coal micropore than CO2
      molecule. The coal micropores are occupied by H2O molecules that cannot provide
      extra space for CO2 adsorption, which may leads to the reduction of CO2
      adsorption capacity. However, without considering factors of micropore and oxygen
      functional groups, the co-adsorption mechanisms of CO2 and adsorbed H2O molecule
      are not clear. Density functional theory (DFT) calculations were performed to
      elucidate the effect of adsorbed H2O to CO2 adsorption. This study reports some
      typical coal-H2O...CO2 complexes, along with a detailed analysis of the geometry,
      energy, electrostatic potential (ESP), atoms in molecules (AIM), reduced density
      gradient (RDG), and energy decomposition analysis (EDA). The results show that
      H2O molecule can more stably adsorb on the aromatic ring surface than CO2
      molecule, and the absolute values of local ESP maximum and minimum of H2O cluster
      are greater than CO2. AIM analysis shows a detailed interaction path and strength
      between atoms in CO2 and H2O, and RDG analysis shows that the interactions among
      CO2, H2O, and coal model belong to weak van der Waals force. EDA indicates that
      electrostatic and long-range dispersion terms play a primary role in the co
      adsorption of CO2 and H2O. According to the DFT calculated results without
      considering micropore structure and functional group, it is shown that the
      adsorbed H2O can promote CO2 adsorption on the coal surface. These results
      demonstrate that the micropore factor plays a dominant role in affecting CO2
      adsorption capacity, the attractive interaction of adsorbed H2O to CO2 makes
      little contribution.

PMID- 28500520
TI  - Theoretical study of noncovalent interactions in XCN...YO2H (X = F, Cl, Br, I; Y
      = P, As, Sb) complexes.
AB  - Noncovalent interactions in XCN...YO2H (X = F, Cl, Br, I; Y = P, As, Sb)
      complexes were investigated using ab initio calculations at the MP2/aug-cc-pVDZ
      level of theory. There are four different configurations of these complexes, and
      the complexes are formed via hydrogen bonds, halogen bonds, pi-hole interactions,
      or dual interactions. An examination of binding distances and interaction
      energies suggested that pi-hole bonds are more stable than the other
      interactions. Molecular electrostatic potentials, electron densities, second
      order stabilization energies, and electron density differences were computed to
      study the character of these interactions.

PMID- 28500521
TI  - Overview of the Diverse Roles of Bacterial and Archaeal Cytoskeletons.
AB  - As discovered over the past 25 years, the cytoskeletons of bacteria and archaea
      are complex systems of proteins whose central components are dynamic cytomotive
      filaments. They perform roles in cell division, DNA partitioning, cell shape
      determination and the organisation of intracellular components. The protofilament
      structures and polymerisation activities of various actin-like, tubulin-like and
      ESCRT-like proteins of prokaryotes closely resemble their eukaryotic counterparts
      but show greater diversity. Their activities are modulated by a wide range of
      accessory proteins but these do not include homologues of the motor proteins that
      supplement filament dynamics to aid eukaryotic cell motility. Numerous other
      filamentous proteins, some related to eukaryotic IF-proteins/lamins and dynamins
      etc, seem to perform structural roles similar to those in eukaryotes.

PMID- 28500522
TI  - E. coli Cell Cycle Machinery.
AB  - Cytokinesis in E. coli is organized by a cytoskeletal element designated the Z
      ring. The Z ring is formed at midcell by the coalescence of FtsZ filaments
      tethered to the membrane by interaction of FtsZ's conserved C-terminal peptide
      (CCTP) with two membrane-associated proteins, FtsA and ZipA. Although interaction
      between an FtsZ monomer and either of these proteins is of low affinity, high
      affinity is achieved through avidity - polymerization linked CCTPs interacting
      with the membrane tethers. The placement of the Z ring at midcell is ensured by
      antagonists of FtsZ polymerization that are positioned within the cell and target
      FtsZ filaments through the CCTP. The placement of the ring is reinforced by a
      protein network that extends from the terminus (Ter) region of the chromosome to
      the Z ring. Once the Z ring is established, additional proteins are recruited
      through interaction with FtsA, to form the divisome. The assembled divisome is
      then activated by FtsN to carry out septal peptidoglycan synthesis, with a
      dynamic Z ring serving as a guide for septum formation. As the septum forms, the
      cell wall is split by spatially regulated hydrolases and the outer membrane
      invaginates in step with the aid of a transenvelope complex to yield progeny
      cells.

PMID- 28500526
TI  - Intermediate Filaments Supporting Cell Shape and Growth in Bacteria.
AB  - For years intermediate filaments (IF), belonging to the third class of
      filamentous cytoskeletal proteins alongside microtubules and actin filaments,
      were thought to be exclusive to metazoan cells. Structurally these eukaryote IFs
      are very well defined, consisting of globular head and tail domains, which flank
      the central rod-domain. This central domain is dominated by an alpha-helical
      secondary structure predisposed to form the characteristic coiled-coil, parallel
      homo-dimer. These elementary dimers can further associate, both laterally and
      longitudinally, generating a variety of filament-networks built from filaments in
      the range of 10 nm in diameter. The general role of these filaments with their
      characteristic mechano-elastic properties both in the cytoplasm and in the
      nucleus of eukaryote cells is to provide mechanical strength and a scaffold
      supporting diverse shapes and cellular functions.Since 2003, after the first
      bacterial IF-like protein, crescentin was identified, it has been evident that
      bacteria also employ filamentous networks, other than those built from bacterial
      tubulin or actin homologues, in order to support their cell shape, growth and, in
      some cases, division. Intriguingly, compared to their eukaryote counterparts, the
      group of bacterial IF-like proteins shows much wider structural diversity. The
      sizes of both the head and tail domains are markedly reduced and there is great
      variation in the length of the central rod-domain. Furthermore, bacterial rod
      domains often lack the sub-domain organisation of eukaryote IFs that is the
      defining feature of the IF-family. However, the fascinating display of
      filamentous assemblies, including rope, striated cables and hexagonal laces
      together with the conditions required for their formation both in vitro and in
      vivo strongly resemble that of eukaryote IFs suggesting that these bacterial
      proteins are deservedly classified as part of the IF-family and that the current
      definition should be relaxed slightly to allow their inclusion. The lack of
      extensive head and tail domains may well make the bacterial proteins more
      amenable for structural characterisation, which will be essential for
      establishing the mechanism for their association into filaments. What is more,
      the well-developed tools for bacterial manipulations provide an excellent
      opportunity of studying the bacterial systems with the prospect of making
      significant progress in our understanding of the general underlying principles of
      intermediate filament assemblies.

PMID- 28500525
TI  - FtsZ Constriction Force - Curved Protofilaments Bending Membranes.
AB  - FtsZ assembles in vitro into protofilaments (pfs) that are one subunit thick and
      ~50 subunits long. In vivo these pfs assemble further into the Z ring, which,
      along with accessory division proteins, constricts to divide the cell. We have
      reconstituted Z rings in liposomes in vitro, using pure FtsZ that was modified
      with a membrane targeting sequence to directly bind the membrane. This FtsZ-mts
      assembled Z rings and constricted the liposomes without any accessory proteins.
      We proposed that the force for constriction was generated by a conformational
      change from straight to curved pfs. Evidence supporting this mechanism came from
      switching the membrane tether to the opposite side of the pf. These switched
      tether pfs assembled "inside-out" Z rings, and squeezed the liposomes from the
      outside, as expected for the bending model. We propose three steps for the full
      process of cytokinesis: (a) pf bending generates a constriction force on the
      inner membrane, but the rigid peptidoglycan wall initially prevents any
      invagination; (b) downstream proteins associate to the Z ring and remodel the
      peptidoglycan, permitting it to follow the constricting FtsZ to a diameter of
      ~250 nm; the final steps of closure of the septum and membrane fusion are
      achieved by excess membrane synthesis and membrane fluctuations.

PMID- 28500527
TI  - FtsZ-ring Architecture and Its Control by MinCD.
AB  - In bacteria and archaea, the most widespread cell division system is based on the
      tubulin homologue FtsZ protein, whose filaments form the cytokinetic Z-ring. FtsZ
      filaments are tethered to the membrane by anchors such as FtsA and SepF and are
      regulated by accessory proteins. One such set of proteins is responsible for Z
      ring's spatiotemporal regulation, essential for the production of two equal-sized
      daughter cells. Here, we describe how our still partial understanding of the FtsZ
      based cell division process has been progressed by visualising near-atomic
      structures of Z-rings and complexes that control Z-ring positioning in cells,
      most notably the MinCDE and Noc systems that act by negatively regulating FtsZ
      filaments. We summarise available data and how they inform mechanistic models for
      the cell division process.

PMID- 28500528
TI  - Bacterial Actins.
AB  - A diverse set of protein polymers, structurally related to actin filaments
      contributes to the organization of bacterial cells as cytomotive or cytoskeletal
      filaments. This chapter describes actin homologs encoded by bacterial
      chromosomes. MamK filaments, unique to magnetotactic bacteria, help establishing
      magnetic biological compasses by interacting with magnetosomes. Magnetosomes are
      intracellular membrane invaginations containing biomineralized crystals of iron
      oxide that are positioned by MamK along the long-axis of the cell. FtsA is
      widespread across bacteria and it is one of the earliest components of the
      divisome to arrive at midcell, where it anchors the cell division machinery to
      the membrane. FtsA binds directly to FtsZ filaments and to the membrane through
      its C-terminus. FtsA shows altered domain architecture when compared to the
      canonical actin fold. FtsA's subdomain 1C replaces subdomain 1B of other members
      of the actin family and is located on the opposite side of the molecule.
      Nevertheless, when FtsA assembles into protofilaments, the protofilament
      structure is preserved, as subdomain 1C replaces subdomain IB of the following
      subunit in a canonical actin filament. MreB has an essential role in shape
      maintenance of most rod-shaped bacteria. Unusually, MreB filaments assemble from
      two protofilaments in a flat and antiparallel arrangement. This non-polar
      architecture implies that both MreB filament ends are structurally identical.
      MreB filaments bind directly to membranes where they interact with both cytosolic
      and membrane proteins, thereby forming a key component of the elongasome. MreB
      filaments in cells are short and dynamic, moving around the long axis of rod
      shaped cells, sensing curvature of the membrane and being implicated in
      peptidoglycan synthesis.

PMID- 28500524
TI  - Cytoskeletal Proteins in Caulobacter crescentus: Spatial Orchestrators of Cell
      Cycle Progression, Development, and Cell Shape.
AB  - Caulobacter crescentus, an aquatic Gram-negative alpha-proteobacterium, is
      dimorphic, as a result of asymmetric cell divisions that give rise to a free
      swimming swarmer daughter cell and a stationary stalked daughter. Cell polarity
      of vibrioid C. crescentus cells is marked by the presence of a stalk at one end
      in the stationary form and a polar flagellum in the motile form. Progression
      through the cell cycle and execution of the associated morphogenetic events are
      tightly controlled through regulation of the abundance and activity of key
      proteins. In synergy with the regulation of protein abundance or activity,
      cytoskeletal elements are key contributors to cell cycle progression through
      spatial regulation of developmental processes. These include: polarity
      establishment and maintenance, DNA segregation, cytokinesis, and cell elongation.
      Cytoskeletal proteins in C. crescentus are additionally required to maintain its
      rod shape, curvature, and pole morphology. In this chapter, we explore the
      mechanisms through which cytoskeletal proteins in C. crescentus orchestrate
      developmental processes by acting as scaffolds for protein recruitment,
      generating force, and/or restricting or directing the motion of molecular
      machines. We discuss each cytoskeletal element in turn, beginning with those
      important for organization of molecules at the cell poles and chromosome
      segregation, then cytokinesis, and finally cell shape.

PMID- 28500529
TI  - Bacterial Nucleoid Occlusion: Multiple Mechanisms for Preventing Chromosome
      Bisection During Cell Division.
AB  - In most bacteria cell division is driven by the prokaryotic tubulin homolog,
      FtsZ, which forms the cytokinetic Z ring. Cell survival demands both the spatial
      and temporal accuracy of this process to ensure that equal progeny are produced
      with intact genomes. While mechanisms preventing septum formation at the cell
      poles have been known for decades, the means by which the bacterial nucleoid is
      spared from bisection during cell division, called nucleoid exclusion (NO), have
      only recently been deduced. The NO theory was originally posited decades ago
      based on the key observation that the cell division machinery appeared to be
      inhibited from forming near the bacterial nucleoid. However, what might drive the
      NO process was unclear. Within the last 10 years specific proteins have been
      identified as important mediators of NO. Arguably the best studied NO mechanisms
      are those employed by the Escherichia coli SlmA and Bacillus subtilis Noc
      proteins. Both proteins bind specific DNA sequences within selected chromosomal
      regions to act as timing devices. However, Noc and SlmA contain completely
      different structural folds and utilize distinct NO mechanisms. Recent studies
      have identified additional processes and factors that participate in preventing
      nucleoid septation during cell division. These combined data show multiple levels
      of redundancy as well as a striking diversity of mechanisms have evolved to
      protect cells against catastrophic bisection of the nucleoid. Here we discuss
      these recent findings with particular emphasis on what is known about the
      molecular underpinnings of specific NO machinery and processes.

PMID- 28500523
TI  - Cell Cycle Machinery in Bacillus subtilis.
AB  - Bacillus subtilis is the best described member of the Gram positive bacteria. It
      is a typical rod shaped bacterium and grows by elongation in its long axis,
      before dividing at mid cell to generate two similar daughter cells. B. subtilis
      is a particularly interesting model for cell cycle studies because it also
      carries out a modified, asymmetrical division during endospore formation, which
      can be simply induced by starvation. Cell growth occurs strictly by elongation of
      the rod, which maintains a constant diameter at all growth rates. This process
      involves expansion of the cell wall, requiring intercalation of new peptidoglycan
      and teichoic acid material, as well as controlled hydrolysis of existing wall
      material. Actin-like MreB proteins are the key spatial regulators that
      orchestrate the plethora of enzymes needed for cell elongation, many of which are
      thought to assemble into functional complexes called elongasomes. Cell division
      requires a switch in the orientation of cell wall synthesis and is organised by a
      tubulin-like protein FtsZ. FtsZ forms a ring-like structure at the site of
      impending division, which is specified by a range of mainly negative regulators.
      There it recruits a set of dedicated division proteins to form a structure called
      the divisome, which brings about the process of division. During sporulation,
      both the positioning and fine structure of the division septum are altered, and
      again, several dedicated proteins that contribute specifically to this process
      have been identified. This chapter summarises our current understanding of
      elongation and division in B. subtilis, with particular emphasis on the
      cytoskeletal proteins MreB and FtsZ, and highlights where the major gaps in our
      understanding remain.

PMID- 28500530
TI  - Structure and Dynamics of Actin-Like Cytomotive Filaments in Plasmid Segregation.
AB  - One of the well-known functions of the bacterial cytoskeleton is plasmid
      segregation. Type II plasmid segregation systems, among the best characterized
      with respect to the mechanism of action, possess an actin-like cytomotive
      filament as the motor component. This chapter describes the essential components
      of the plasmid segregation machinery and their mechanism of action, concentrating
      on the actin-like protein family of the bacterial cytoskeleton. The structures of
      the actin-like filaments depend on their nucleotide state and these in turn
      contribute to the dynamics of the filaments. The components that link the
      filaments to the plasmid DNA also regulate filament dynamics. The modulation of
      the dynamics facilitates the cytomotive filament to function as a mitotic spindle
      with a minimal number of components.

PMID- 28500531
TI  - Tubulin-Like Proteins in Prokaryotic DNA Positioning.
AB  - A family of tubulin-related proteins (TubZs) has been identified in prokaryotes
      as being important for the inheritance of virulence plasmids of several
      pathogenic Bacilli and also being implicated in the lysogenic life cycle of
      several bacteriophages. Cell biological studies and reconstitution experiments
      revealed that TubZs function as prokaryotic cytomotive filaments, providing one
      dimensional motive forces. Plasmid-borne TubZ filaments most likely transport
      plasmid centromeric complexes by depolymerisation, pulling on the plasmid DNA, in
      vitro. In contrast, phage-borne TubZ (PhuZ) pushes bacteriophage particles
      (virions) to mid cell by filament growth. Structural studies by both
      crystallography and electron cryo-microscopy of multiple proteins, both from the
      plasmid partitioning sub-group and the bacteriophage virion centring group of
      TubZ homologues, allow a detailed consideration of the structural phylogeny of
      the group as a whole, while complete structures of both crystallographic
      protofilaments at high resolution and fully polymerised filaments at intermediate
      resolution by cryo-EM have revealed details of the polymerisation behaviour of
      both TubZ sub-groups.

PMID- 28500532
TI  - The Structure, Function and Roles of the Archaeal ESCRT Apparatus.
AB  - Although morphologically resembling bacteria, archaea constitute a distinct
      domain of life with a closer affiliation to eukaryotes than to bacteria. This
      similarity is seen in the machineries for a number of essential cellular
      processes, including DNA replication and gene transcription. Perhaps
      surprisingly, given their prokaryotic morphology, some archaea also possess a
      core cell division apparatus that is related to that involved in the final stages
      of membrane abscission in vertebrate cells, the ESCRT machinery.

PMID- 28500533
TI  - Archaeal Actin-Family Filament Systems.
AB  - Actin represents one of the most abundant and conserved eukaryotic proteins over
      time, and has an important role in many different cellular processes such as cell
      shape determination, motility, force generation, cytokinesis, amongst many
      others. Eukaryotic actin has been studied for decades and was for a long time
      considered a eukaryote-specific trait. However, in the early 2000s a bacterial
      actin homolog, MreB, was identified, characterized and found to have a
      cytoskeletal function and group within the superfamily of actin proteins. More
      recently, an actin cytoskeleton was also identified in archaea. The genome of the
      hyperthermophilic crenarchaeon Pyrobaculum calidifontis contains a five-gene
      cluster named Arcade encoding for an actin homolog, Crenactin, polymerizing into
      helical filaments spanning the whole length of the cell. Phylogenetic and
      structural studies place Crenactin closer to the eukaryotic actin than to the
      bacterial homologues. A significant difference, however, is that Crenactin can
      form single helical filaments in addition to filaments containing two intertwined
      proto filaments. The genome of the recently discovered Lokiarchaeota encodes
      several different actin homologues, termed Lokiactins, which are even more
      closely related to the eukaryotic actin than Crenactin. A primitive, dynamic
      actin-based cytoskeleton in archaea could have enabled the engulfment of the
      alphaproteobacterial progenitor of the mitochondria, a key-event in the evolution
      of eukaryotes.

PMID- 28500534
TI  - The Tubulin Superfamily in Archaea.
AB  - In comparison with bacteria and eukaryotes, the large and diverse group of
      microorganisms known as archaea possess a great diversity of cytoskeletal
      proteins, including members of the tubulin superfamily. Many species contain
      FtsZ, CetZ and even possible tubulins; however, some major taxonomic groups do
      not contain any member of the tubulin superfamily. Studies using the model
      archaeon, Halferax volcanii have recently been instrumental in defining the
      fundamental roles of FtsZ and CetZ in archaeal cell division and cell shape
      regulation. Structural studies of archaeal tubulin superfamily proteins provide a
      definitive contribution to the cytoskeletal field, showing which protein-types
      must have developed prior to the divergence of archaea and eukaryotes. Several
      regions of the globular core domain - the "signature" motifs - combine in the 3D
      structure of the common molecular fold to form the GTP-binding site. They are the
      most conserved sequence elements and provide the primary basis for identification
      of new superfamily members through homology searches. The currently well
      characterised proteins also all share a common mechanism of GTP-dependent
      polymerisation, in which GTP molecules are sandwiched between successive subunits
      that are arranged in a head-to-tail manner. However, some poorly-characterised
      archaeal protein families retain only some of the signature motifs and are
      unlikely to be capable of dynamic polymerisation, since the promotion of
      depolymerisation by hydrolysis to GDP depends on contributions from both subunits
      that sandwich the nucleotide in the polymer.

PMID- 28500535
TI  - Reconstitution of Protein Dynamics Involved in Bacterial Cell Division.
AB  - Even simple cells like bacteria have precisely regulated cellular anatomies,
      which allow them to grow, divide and to respond to internal or external cues with
      high fidelity. How spatial and temporal intracellular organization in prokaryotic
      cells is achieved and maintained on the basis of locally interacting proteins
      still remains largely a mystery. Bulk biochemical assays with purified components
      and in vivo experiments help us to approach key cellular processes from two
      opposite ends, in terms of minimal and maximal complexity. However, to understand
      how cellular phenomena emerge, that are more than the sum of their parts, we have
      to assemble cellular subsystems step by step from the bottom up. Here, we review
      recent in vitro reconstitution experiments with proteins of the bacterial cell
      division machinery and illustrate how they help to shed light on fundamental
      cellular mechanisms that constitute spatiotemporal order and regulate cell
      division.

PMID- 28500536
TI  - Benzocoumarin-Styryl Hybrids: Aggregation and Viscosity Induced Emission
      Enhancement.
AB  - Two benzo[h]chromen-3-yl)ethylidene) malononitrile styryl hybrid dyes are
      synthesized and characterized by NMR and elemental analysis. One is based on
      nitrogen donor and other on oxygen (3b and 3b respectively). Dyes are low
      emissive in the solution but dramatically showed increase in emission intensity
      in aggregates form in the THF (tetrahydrofuran) /water system. Dyes are also
      sensitive to viscosity and showed increased emission intensity in the DCM:PEG 400
      system and DMF:PEG 400 system respectively. Dyes 3a and 3b showed higher
      viscosity sensitivity constant (0.67 and 0.39 respectively) in DMF:PEG 400 system
      compared to DCM:PEG 400 (0.47 and 0.21 respectively) system which is contrary to
      the traditional concept of FMRs. Results shows that lowering of twisted
      intramolecular charge transfer (TICT) and increase in intramolecular charge
      transfer (ICT) in the excited state could be the reason for such behavior in the
      aggregate and highly viscous state. This study may provide the new insights into
      the field of AIEE and FMR research of such hybrid molecules.

PMID- 28500537
TI  - Zhongxian Lin: Founder of color psychology in China.

PMID- 28500538
TI  - Lian-Cang Xu: the founder of management psychology in China.

PMID- 28500539
TI  - Hybrid PET/CT and PET/MRI imaging of vulnerable coronary plaque and myocardial
      scar tissue in acute myocardial infarction.
AB  - BACKGROUND: Following an acute coronary syndrome, combined CT and PET with 18F
      NaF can identify coronary atherosclerotic plaques that have ruptured or eroded.
      However, the processes behind 18F-NaF uptake in vulnerable plaques remain
      unclear. METHODS AND RESULTS: Ten patients with STEMI were scanned after 18F-NaF
      injection, for 75 minutes in a Siemens PET/MR scanner using delayed enhancement
      (LGE). They were then scanned in a Siemens PET/CT scanner for 10 minutes. Tissue
      to-background ratio (TBR) was compared between the culprit lesion in the IRA and
      remote non-culprit lesions in an effort to independently validate prior studies.
      Additionally, we performed a proof-of-principle study comparing TBR in scar
      tissue and remote myocardium using LGE images and PET/MR or PET/CT data. From the
      33 coronary lesions detected on PET/CT, TBRs for culprit lesions were higher than
      for non-culprit lesions (TBR = 2.11 +/- 0.45 vs 1.46 +/- 0.48; P < 0.001).
      Interestingly, the TBR measured on the PET/CT was higher for infarcted myocardium
      than for remote myocardium (TBR = 0.81 +/- 0.10 vs 0.71 +/- 0.05; P = 0.003).
      These results were confirmed using the PET/MR data (TBR = 0.81 +/- 0.10 for scar,
      TBR = 0.71 +/- 0.06 for healthy myocardium, P = 0.03). CONCLUSIONS: We confirmed
      the potential of 18F-NaF PET/CT imaging to detect vulnerable coronary lesions.
      Moreover, we demonstrated proof-of-principle that 18F-NaF concurrently detects
      myocardial scar tissue.

PMID- 28500540
TI  - Prediction of sudden cardiac death in patients with chronic heart failure by
      regional washout rate in cardiac MIBG SPECT imaging.
AB  - BACKGROUND: The sympathetic nervous system provides an important trigger for
      major arrhythmic events through regional heterogeneity of sympathetic activity,
      which could be evaluated by SPECT imaging as the regional MIBG washout rate (WR).
      There is little information available on the prognostic value of regional WR in
      SPECT imaging for the prediction of sudden cardiac death (SCD) in patients with
      chronic heart failure (CHF). METHODS: We studied 73 CHF outpatients with LVEF <
      40%. At study entry, the regional WR was measured in 17 segments on the polar
      map. We defined abnormal regional WR as both the regional WR range (maximum -
      minimum regional WR) and maximum regional WR > mean value + 2SD obtained in 15
      normal controls. RESULTS: During a mean follow-up of 7.5 +/- 4.1 years, 15 of 73
      patients had SCD. The abnormal regional WR and abnormal global WR on planar
      images were significantly and independently associated with SCD. Patients with
      both the abnormal regional WR and global WR had a significantly higher risk of
      SCD than those with none of these criteria. CONCLUSIONS: The analysis of regional
      MIBG WR on SPECT imaging provides additional prognostic value to global WR on
      planar images for SCD prediction in CHF patients.

PMID- 28500541
TI  - Ambivalence over emotional expression, intrusive thoughts, and posttraumatic
      stress symptoms among Chinese American breast cancer survivors.
AB  - OBJECTIVE: Posttraumatic stress symptoms (PTSS) are common among breast cancer
      survivors. However, the association and the underlying mediating mechanism
      between psychosocial factors and PTSS were rarely investigated among breast
      cancer survivors. Previous studies have suggested the importance of emotional
      expression in cancer survivors' PTSS. This study examined the association between
      ambivalence over emotional expression (AEE; defined as the conflict between the
      desire to express feelings and the fear of its consequences) and PTSS, and
      proposed intrusive thoughts as the mediators in such an association. We tested
      this proposed mediation model among Chinese breast cancer survivors whose culture
      discourages emotional expression. METHODS: Participants were 118 Chinese-speaking
      breast cancer survivors in the USA, who were diagnosed with breast cancer of
      stages 0-III within the past 5 years. They completed questionnaires measuring
      their levels of AEE, PTSS, and intrusive thoughts. RESULTS: AEE was positively
      associated with intrusive thoughts (r = 0.43, p < 01), which were positively
      associated with the arousal and avoidance subscales of PTSS (r = 0.68 and r =
      0.62, respectively, p < .01). Path analysis supported a partial mediation model
      with an indirect effect from AEE to the latent variable of PTSS (with both
      arousal and avoidance as indicators) via intrusive thoughts (beta = 0.29; 95% CI=
      0.18, 0.42) and the direct effect from AEE to the latent variable of PTSS (beta =
      0.21, 95% CI = 0.07, 0.35), all p < .001. CONCLUSIONS: Those who are highly
      ambivalent about emotion expression tend to have higher PTSS, and this may be
      partially due to the lack of opportunities to discuss emotional events, thereby
      increasing the repetitive cancer-related negative thoughts. Intervention for PTSS
      should consider helping cancer patients to develop adaptive emotional regulation
      strategies to reduce the detrimental effects of cancer-related intrusive
      thoughts.

PMID- 28500542
TI  - Self-report of symptoms in children with cancer younger than 8 years of age: a
      systematic review.
AB  - OBJECTIVE: The study's objective was to summarize the psychometric evaluation of
      self-report symptom instruments used in children with cancer younger than 8 years
      of age. METHODS: We conducted electronic searches of Ovid Medline, EMBASE,
      PsycInfo, Science Citation, Social Science Citation (Web of Science), and CINAHL.
      We included studies of children with cancer in which their self-report symptoms
      had been quantified and in which results were described for those younger than 8
      years of age. The search was restricted to publications in English. Two reviewers
      screened studies and abstracted all data in duplicate. Descriptive analysis of
      reliability and validity was performed. RESULTS: Thirteen studies were included.
      Only one study recruited children <8 years alone. Most studies described
      reliability and validity in a wider age range cohort in which most children were
      older than 8 years of age. Of the eight studies that evaluated reliability within
      the younger age group, six raised concerns about poor internal consistency with
      Cronbach's alpha <0.7 in at least one dimension. Concerns about test re-test
      reliability and inter-rater reliability were also observed. None of the studies
      evaluated validity. CONCLUSIONS: We failed to demonstrate that currently
      available instruments to measure self-report symptoms are reliable or valid
      specifically for children with cancer younger than 8 years of age. Development of
      psychometrically robust instruments for younger children should be a priority.

PMID- 28500543
TI  - Impact of spin label rigidity on extent and accuracy of distance information from
      PRE data.
AB  - Paramagnetic relaxation enhancement (PRE) is a versatile tool for NMR
      spectroscopic structural and kinetic studies in biological macromolecules. Here,
      we compare the quality of PRE data derived from two spin labels with markedly
      different dynamic properties for large RNAs using the I-A riboswitch aptamer
      domain (78 nt) from Mesoplamsa florum as model system. We designed two I-A
      aptamer constructs that were spin-labeled by noncovalent hybridization of short
      spin-labeled oligomer fragments. As an example of a flexible spin label, UreidoU
      TEMPO was incorporated into the 3' terminal end of helix P1 while, the recently
      developed rigid spin-label Cm was incorporated in the 5' terminal end of helix
      P1. We determined PRE rates obtained from aromatic 13C bound proton intensities
      and compared these rates to PREs derived from imino proton intensities in this
      sizeable RNA (~78 nt). PRE restraints derived from both imino and aromatic
      protons yielded similar data quality, and hence can both be reliably used for PRE
      determination. For NMR, the data quality derived from the rigid spin label Cm is
      slightly better than the data quality for the flexible UreidoTEMPO as judged by
      comparison of the structural agreement with the I-A aptamer crystal structure
      (3SKI).

PMID- 28500545
TI  - Nocardia tengchongensis sp. nov., isolated from a soil sample.
AB  - The taxonomic status was determined of two actinomycetes, designated CFH S0057T
      and CFH S0065, that were isolated from soil samples collected from an extinct
      volcano in Tengchong county, Yunnan province, south-west China. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strains CFH S0057T and CFH
      S0065 belong to the genus Nocardia and formed a single clade within this genus.
      The two isolates were able to grow at 4-45  degrees C, pH 5.0-7.0 and with a NaCl
      tolerance up to 5.0% (w/v). The whole-cell hydrolysates were rich in meso
      diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were
      present. Strains CFH S0057T and CFH S0065 exhibited a menaquinone system with MK
      8 (H4, omega cyclo), and the major polar lipids consisted of
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol,
      phosphatidylinositol mannoside and one unidentified phospholipid. Major fatty
      acids were C16:0, Summed features 3, C18:1 omega9c and C18:0 10-methyl (TBSA).
      The genomic DNA G + C contents of strains CFH S0057T and CFH S0065 were 65.7 and
      66.1 mol%, respectively. The combined genotypic, phenotypic and chemotaxonomic
      results indicated the isolates are considered to represent a novel species of the
      genus Nocardia, for which the name Nocardia tengchongensis sp. nov. is proposed.
      The type strain is CFH S0057T (= KCTC 29485T = JCM 30083T).

PMID- 28500544
TI  - Diversity and plant growth promoting properties of rhizobia isolated from root
      nodules of Ononis arvensis.
AB  - This is the first report describing isolates from root nodules of Ononis arvensis
      (field restharrow). The aim of this investigation was to describe the diversity,
      phylogeny, and plant growth promoting features of microsymbionts of O. arvensis,
      i.e., a legume plant growing in different places of the southern part of Poland.
      Twenty-nine bacterial isolates were characterized in terms of their phenotypic
      properties, genome fingerprinting, and comparative analysis of their 16S rRNA,
      nodC and acdS gene sequences. Based on the nodC and 16S rRNA gene phylogenies,
      the O. arvensis symbionts were grouped close to bacteria of the genera Rhizobium
      and Mesorhizobium, which formed monophyletic clusters. The acdS gene sequences of
      all the isolates tested exhibited the highest similarities to the corresponding
      gene sequences of genus Mesorhizobium strains. The presence of the acdS genes in
      the genomes of rhizobia specific for O. arvensis implies that these bacteria may
      promote the growth and development of their host plant in stress conditions. The
      isolated bacteria showed a high genomic diversity and, in the BOX-PCR reaction,
      all of them (except three) exhibited DNA fingerprints specific only for them. Our
      studies showed that restharrow isolates formed effective symbiotic interactions
      with their native host (O. arvensis) and Ononis spinosa but not with Trifolium
      repens and Medicago sativa belonging to the same tribe Trifolieae as Ononis
      species and not with Lotus corniculatus, representing the tribe Loteae.

PMID- 28500547
TI  - Effects of Se on the growth, tolerance, and antioxidative systems of three
      alfalfa cultivars.
AB  - The aim of this study was to evaluate the selenium (Se) tolerance and exploit the
      physiological mechanisms in roots, stem, and leaves of three alfalfa cultivars to
      different concentrations of Se for 60 days. Among three cultivars, Medicago
      sativa ssp. displayed the highest Se concentrations in tissues, the largest Se
      amount in aerial parts, the highest bioconcentration factor (BCF) in aerial
      parts, and translocation factor (TF) under Se stress. Under Se stress, induced
      O2*- production in roots and leaves and increases in free proline and activities
      of antioxidative enzymes were observed in M. sativa ssp. Based on the above
      results, it is concluded that M. sativa ssp. is superior to the other two
      cultivars for Se phytoremediation, and its well-coordinated physiological changes
      under Se stress confer the great Se tolerance of this cultivar.

PMID- 28500546
TI  - Quantitative image analysis of polyhydroxyalkanoates inclusions from microbial
      mixed cultures under different SBR operation strategies.
AB  - Polyhydroxyalkanoates (PHAs) produced from mixed microbial cultures (MMC),
      regarded as potential substitutes of petrochemical plastics, can be found as
      intracellular granules in various microorganisms under limited nutrient
      conditions and excess of carbon source. PHA is traditionally quantified by
      laborious and time-consuming chromatography analysis, and a simpler and faster
      method to assess PHA contents from MMC, such as quantitative image analysis
      (QIA), is of great interest. The main purpose of the present work was to upgrade
      a previously developed QIA methodology (as reported by Mesquita et al. (Anal Chim
      Acta 770:36-44, 2013a, Anal Chim Acta 865:8-15, 2015)) for MMC intracellular PHA
      contents quantification, increase the studied intracellular PHA concentration
      range, and extend to different sequencing batch reactor (SBR) operation
      strategies. Therefore, the operation of a new aerobic dynamic feeding (ADF) SBR
      allowed further extending the studied operating conditions, dataset, and range of
      the MMC intracellular PHA contents from the previously reported anaerobic/aerobic
      cycle SBR. Nile Blue A (NBA) staining was employed for epifluorescence microscope
      visualization and image acquisition, further fed to a custom developed QIA. Data
      from each of the feast and famine cycles of both SBR were individually processed
      using chemometrics analysis, obtaining the correspondent partial least squares
      (PLS) models. The PHA concentrations determined from PLS models were further
      plotted against the results obtained in the standard chromatographic method. For
      both SBR, the predicted ability was higher at the end of the feast stage than for
      the famine stage. Indeed, an independent feast and famine QIA data treatment was
      found to be fundamental to obtain the best prediction abilities. Furthermore, a
      promising overall correlation (R 2 of 0.83) could be found combining the overall
      QIA data regarding the PHA prediction up to a concentration of 1785.1 mg L-1
      (37.3 wt%). Thus, the results confirm that the presented QIA methodology can be
      seen as promising for estimating higher intracellular PHA concentrations for a
      larger reactors operation systems and further extending the prediction range of
      previous studies.

PMID- 28500549
TI  - Adsorption affinity and selectivity of 3-ureidopropyltriethoxysilane grafted oil
      palm empty fruit bunches towards mercury ions.
AB  - This study was conducted to investigate the potential application of oil palm
      empty fruit branches (OPEFB) as adsorbents to remove organic methylmercurry,
      MeHg(II), and inorganic Hg(II) from aqueous solution. The OPEFB was
      functionalized with amine containing ligand namely 3-ureidopropyltriethoxysilane
      (UPTES) aiming for better adsorption performance towards both mercury ions. The
      adsorption was found to be dependent on initial pH, initial concentraton,
      temperatures, and contact time. The maximum adsorption capacities (Qm.exp) of
      Hg(II) adsorption onto OPEFB and UPTES-OPEFB were 0.226 and 0.773 mmol/g,
      respectively. The Qm.exp of MeHg(II) onto OPEFB, however, was higher than UPTES
      OPEFB. The adsorption kinetic data obeyed the Elovich model and the adsorption
      was controlled by the film-diffusion step. The calculated thermodynamic
      parameters indicate an endothermic adsorption process. Adsorption data analysis
      indicates that the adsorption mechanism may include ion-exchange, complexation,
      and physisorption interactions. The potential applications of adsorbents were
      demonstrated using oilfield produced water and natural gas condensate. The UPTES
      OPEFB offered higher selectivity towards both mercury ions than OPEFB. The
      regenerability studies indicated that the adsorbent could be reused for multiple
      cycles.

PMID- 28500548
TI  - Decontamination of arsenic(V)-contained liquid phase utilizing Fe3O4/bone char
      nanocomposite encapsulated in chitosan biopolymer.
AB  - The application of a novel nanocomposite synthesized through the combination of
      Fe3O4 nanoparticles and bone char particles for the adsorption of As(V) ions in
      the aquatic medium was investigated. As-prepared nanocomposite was immobilized by
      using chitosan biopolymer. The characterization of the nanocomposite was
      performed via SEM, XRD, FT-IR, and BET together with the determination of zero
      point charge of the adsorbent surface. As results, the obtained experimental data
      were fitted well with pseudo-first-order kinetic model (R2 = 0.997) and Langmuir
      isotherm model (R2 = 0.990) with the maximum adsorption capacity of about 112
      MUg/g. Increasing the dosage of nanocomposite and initial solute concentration
      led to increasing the adsorption capacity of As(V) ions, while decreasing the
      solution temperature resulted in the enhanced adsorption process. According to
      the results of thermodynamic study, the adsorption of As(V) ions onto the
      nanocomposite was spontaneous and exothermic in nature.

PMID- 28500550
TI  - Reclamation of heavy metals from contaminated soil using organic acid liquid
      generated from food waste: removal of Cd, Cu, and Zn, and soil fertility
      improvement.
AB  - Food waste fermentation generates complicated organic and acidic liquids with low
      pH. In this work, it was found that an organic acid liquid with pH 3.28 and
      volatile low-molecular-weight organic acid (VLMWOA) content of 5.2 g/L could be
      produced from food wastes after 9-day fermentation. When the liquid-to-solid
      ratio was 50:1, temperature was 40  degrees C, and contact time was 0.5-1 day,
      92.9, 78.8, and 52.2% of the Cd, Cu, and Zn in the contaminated soil could be
      washed out using the fermented food waste liquid, respectively. The water
      soluble, acid-soluble, and partly reducible heavy metal fractions can be removed
      after 0.5-day contact time, which was more effective than that using commercially
      available VLMWOAs (29-72% removal), as the former contained microorganisms and
      adequate amounts of nutrients (nitrogen, phosphorous, and exchangeable Na, K, and
      Ca) which favored the washing process of heavy metals. It is thus suggested that
      the organic acid fractions from food waste has a considerable potential for
      reclaiming contaminated soil while improving soil fertility.

PMID- 28500551
TI  - Effect of industrial and domestic ash from biomass combustion, and spent coffee
      grounds, on soil fertility and plant growth: experiments at field conditions.
AB  - An experimental study was conducted at field conditions in order to evaluate the
      effect of application of ash from biomass combustion on some soil fertility
      characteristics and plant growth. Application of 7.5 Mg ha-1 industrial fly ash
      (IA), domestic ash (DA), and a 50:50 mix of domestic ash (DA) and spent coffee
      grounds (SCG) was made in different soil parcels. Lolium perenne seeds were sown
      and the grown biomass was harvested and quantified after 60 days. Soil samples
      from each parcel were also collected after that period and characterized. Both
      soil and grown biomass samples were analyzed for Ca, Mg, Na, K, P, Fe, Mn, Zn,
      and Al contents. Soil pH was determined before and after amendment. All
      applications rose significantly soil pH. Domestic ash, whether combined with
      coffee grounds or not, proved to be efficient at supplying available
      macronutrients Ca, Mg, K, and P to the soil and also reducing availability of Al
      (more than industrial ash). However, it inhibited plant growth, even more when
      combined with spent coffee grounds. As regards to elemental abundance in plant
      tissue, both domestic ash treatments reduced Ca and enhanced Al contents, unlike
      industrial ash, which proved less harmful for the load applied in the soil.
      Hence, it was possible to conclude that application load should be a limiting
      factor for this management option for the studied materials.

PMID- 28500552
TI  - Adsorption of terpenic compounds onto organo-palygorskite.
AB  - Essential oils from aromatic plants are currently mentioned as suitable tools for
      excellent protection of stored grains from insect pest attacks. The present work
      aimed to study the processes of the synthesis insecticidal formulation with clay.
      The active terpenic compounds of essential oil of Eucalyptus globulus (Eg) were
      fixed in the palygorskite by adsorption process. Two sample types of
      palygorskites were used: raw and organo-palygorskite. The palygorskite clays were
      characterized by different physicochemical techniques including X-ray diffraction
      (XRD), Fourier transform infrared (FTIR) analyses, thermogravimetric analysis
      (TG), differential thermal analysis (DTA), Brunauer-Emmet-Teller (BET), and
      scanning electron microscope (SEM). Results reveal that the raw clay has a
      fibrous structure with impurities essential calcite. These structures and
      physicochemical properties of raw palygorskite and organo-palygorskite give it
      the potential of material adsorbent. Results show that the adsorption capacity
      strongly depends on affinity between terpenic compounds and organic cations
      rather than on interlayer distance of organo-palygorskite. The highest adsorption
      capacity of terpenic compounds is acquired with palygorskite interlaced by
      didodecyldimethylammonium bromide (DDDMA). These results validated the potential
      utility of the Paly-DDDMA as adsorbent fibrous clay for the retention of terpenic
      compounds in application of environmental preservation.

PMID- 28500553
TI  - Characterization of rainwater chemical composition after a Southeast Asia haze
      event: insight of transboundary pollutant transport during the northeast monsoon.
AB  - Open biomass burning in Peninsula Malaysia, Sumatra, and parts of the Indochinese
      region is a major source of transboundary haze pollution in the Southeast Asia.
      To study the influence of haze on rainwater chemistry, a short-term investigation
      was carried out during the occurrence of a severe haze episode from March to
      April 2014. Rainwater samples were collected after a prolonged drought and
      analyzed for heavy metals and major ion concentrations using inductively coupled
      plasma mass spectroscopy (ICP-MS) and ion chromatography (IC), respectively. The
      chemical composition and morphology of the solid particulates suspended in
      rainwater were examined using a scanning electron microscope coupled with energy
      dispersive X-ray spectroscopy (SEM-EDS). The dataset was further interpreted
      using enrichment factors (EF), statistical analysis, and a back trajectory (BT)
      model to find the possible sources of the particulates and pollutants. The
      results show a drop in rainwater pH from near neutral (pH 6.54) to acidic (<pH
      4.00) during the haze to non-haze transitional period, suggesting that the
      deposition rate of sulfate and nitrate in the atmosphere via the precipitation
      process was relatively lower compared to the mineral components. Zinc, nitrate,
      and calcium, which were the predominant elements in the first rainwater samples.
      Besides, the results of the SEM-EDS indicated that the zinc was possibly
      originated from anthropogenic activities which are consistent with the results
      obtained from EF. The BT model showed that pollutants transported from the
      mainland of Indo-China and the marine region in the South China Sea were
      responsible for the high pollution event in the study area. These findings can be
      useful in identifying contributions of pollutants from single or multiple sources
      in rainwater samples during haze episodes.

PMID- 28500554
TI  - Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide
      and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study.
AB  - PURPOSE: Circularly permuted TRAIL (CPT) has exhibited promising efficacy as a
      mono-therapy or in combination with thalidomide for patients with multiple
      myeloma (MM). In this phase 2 study, the safety and efficacy of CPT in
      combination with thalidomide and dexamethasone (CPT + TD) was evaluated in
      patients with pretreated relapsed/refractory MM (RRMM). METHODS: Patients who
      received at least two previous therapies for MM were randomly assigned at a 2:1
      ratio to receive treatment with CPT + TD or thalidomide and dexamethasone (TD).
      The primary endpoint was the overall response rate (ORR), and the secondary
      endpoints included progression-free survival (PFS), duration of response (DOR)
      and safety. RESULTS: Overall, 47 patients were assigned to the CPT + TD group,
      and 24 patients were recruited to the TD group. The ORR in the CPT + TD group was
      38.3 vs. 25.0% in the TD group. The median PFS time was 6.7 months for the CPT +
      TD group and 3.1 months for the TD group. The median DORs for the CPT + TD and TD
      groups were 7.1 and 3.2 months, respectively. Most of the adverse effects (AEs)
      were grade 1 or 2. Serious AEs were reported in 19.7% of the patients. No
      treatment-related deaths were reported. CONCLUSION: CPT plus TD could serve as a
      new therapeutic strategy for patients with RRMM. A randomized, double-blind,
      placebo-controlled confirmatory study is currently under way.

PMID- 28500555
TI  - CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo through oxidative
      stress-induced DNA damage and cell apoptosis.
AB  - PURPOSE: The beta-nitrostyrene family has been previously reported to possess
      anticancer property. However, the biological effects of beta-nitrostyrenes on
      ovarian cancer and the underlying mechanisms involved remain unclear. In the
      present study, we synthesized a beta-nitrostyrene derivative, CYT-Rx20 3'-hydroxy
      4'-methoxy-beta-methyl-beta-nitrostyrene), and investigated its anticancer
      effects and the putative pathways of action in ovarian cancer. METHODS: The
      effects of CYT-Rx20 were analyzed using cell viability assay, reactive oxygen
      species (ROS) generation assay, FACS analysis, annexin V staining,
      immunostaining, comet assay, immunoblotting, soft agar assay, migration assay,
      nude mice xenograft study and immunohistochemistry. RESULTS: CYT-Rx20 induced
      cytotoxicity in ovarian cancer cells by promoting cell apoptosis via ROS
      generation and DNA damage. CYT-Rx20-induced cell apoptosis, ROS generation and
      DNA damage were reversed by thiol antioxidants. In addition, CYT-Rx20 inhibited
      ovarian cancer cell migration by regulating the expression of epithelial to
      mesenchymal transition (EMT) markers. In nude mice, CYT-Rx20 inhibited ovarian
      tumor growth accompanied by increased expression of DNA damage marker gammaH2AX
      and decreased expression of EMT marker Vimentin. CONCLUSIONS: CYT-Rx20 inhibits
      ovarian cancer cells in vitro and in vivo, and has the potential to be further
      developed into an anti-ovarian cancer drug clinically.

PMID- 28500556
TI  - Reversing glioma malignancy: a new look at the role of antidepressant drugs as
      adjuvant therapy for glioblastoma multiforme.
AB  - PURPOSE: The role of glioma stem cells (GSCs) in cancer progression is currently
      debated; however, it is hypothesised that this subpopulation is partially
      responsible for therapeutic resistance observed in glioblastoma multiforme (GBM).
      Recent studies have shown that the current treatments not only fail to eliminate
      the GSC population but even promote GSCs through reprogramming of glioma non-stem
      cells to stem cells. Since the standard GBM treatment often requires
      supplementation with adjuvant drugs such as antidepressants, their role in the
      regulation of the heterogeneous nature of GSCs needs evaluation. METHODS: We
      examined the effects of imipramine, amitriptyline, fluoxetine, mirtazapine,
      agomelatine, escitalopram, and temozolomide on the phenotypic signature (CD44,
      Ki67, Nestin, Sox1, and Sox2 expression) of GSCs isolated from a human T98G cell
      line. These drugs were examined in several models of hypoxia (1% oxygen, 2.5%
      oxygen, and a hypoxia-reoxygenation model) as compared to the standard laboratory
      conditions (20% oxygen). RESULTS: We report that antidepressant drugs,
      particularly imipramine and amitriptyline, modulate plasticity, silence the GSC
      profile, and partially reverse the malignant phenotype of GBM. Moreover, we
      observed that, in contrast to temozolomide, these tricyclic antidepressants
      stimulated viability and mitochondrial activity in normal human astrocytes.
      CONCLUSION: The ability of phenotype switching from GSC to non-GSC as stimulated
      by antidepressants (primarily imipramine and amitriptyline) sheds new light on
      the heterogeneous nature of GSC, as well as the role of antidepressants in
      adjuvant GBM therapy.

PMID- 28500557
TI  - Cellular effect and efficacy of carfilzomib depends on cellular net concentration
      gradient.
AB  - PURPOSE: The cellular interrelation between intracellular concentrations of
      unbound carfilzomib, a second-generation proteasome inhibitor, and subsequent
      proteasome inhibition and effect on cell viability are unknown and were evaluated
      for two different exposure regimens: A high dose bolus regime of 500 nM for 1 h
      followed by 47 h in drug-free media vs. 48-h continuous exposure to 10 nM.
      METHODS: Eight multiple myeloma cell lines were exposed to either one of the two
      exposure regimens. We quantified the intracellular unbound carfilzomib fraction
      up to 48 h with a new ultra-performance liquid chromatography coupled to tandem
      mass spectrometry (UPLC/MS/MS) method. Intracellular concentrations were compared
      to simultaneously determined cell viability (AlamarBlue(r) assay) and proteasomal
      subunit activity (ProGloTM assay). RESULTS: Within the first 10 min, the
      proportional intracellular enrichment of unbound carfilzomib was higher (313 nM;
      62.6%) for the exposure to 500 nM compared to 10 nM (1.93 nM; 19.3%). However,
      after 1 h, an intracellular/extracellular concentration equilibrium was reached
      with both settings. At low exposure concentrations, drug removal after 1 h
      diminished carfilzomib efficacy. Moreover, proteasomal activity recovered when
      exposed to 10 nM for 48 h. However, when exposure concentration was high (500 nM)
      proteasome inhibition was complete and sustained even with drug removal after 1
      h. CONCLUSIONS: We demonstrated that the carfilzomib concentration gradient
      determines cellular uptake kinetics. The uptake kinetics in turn affects binding,
      saturation, and activity of the proteasome. Together, these data underscore the
      importance of steep concentrations for the in vitro efficacy of carfilzomib.

PMID- 28500558
TI  - Natural Peer Leaders as Substance Use Prevention Agents: the Teens' Life Choice
      Project.
AB  - In adolescent social groups, natural peer leaders have been found to engage in
      more frequent experimentation with substance use and to possess disproportionate
      power to affect the behavior and social choices of their associated peer
      followers. In the current exploratory study, we used sociometrics and social
      cognitive mapping to identify natural leaders of cliques in a seventh grade
      population and invited the leaders to develop anti-drug presentations for an
      audience of younger peers. The program employed social-psychological approaches
      directed at having leaders proceed from extrinsic inducements to intrinsic
      identification with their persuasive products in the context of the group
      intervention process. The goals of the intervention were to induce substance
      resistant self-persuasion in the leaders and to produce a spread of this
      resistance effect to their peer followers. To test the intervention, we compared
      the substance use behaviors of the selected leaders and their peers to a control
      cohort. The study found preliminary support that the intervention produced
      changes in the substance use behavior among the leaders who participated in the
      intervention, but did not detect a spread to non-leader peers in the short term.
      This descriptive study speaks to the plausibility of employing self-persuasion
      paradigms to bring about change in high-risk behaviors among highly central
      adolescents. In addition, it highlights the viability of applying social
      psychological principles to prevention work and calls for more research in this
      area.

PMID- 28500559
TI  - Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a
      retrospective case series.
AB  - A single institution retrospective evaluation of nivolumab following disease
      progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an
      objective of determining progression free survival (PFS). There is no accepted
      therapy for recurrent GBM after failure of bevacizumab. 16 adults, ages 52-72
      years (median 62), with recurrent GBM were treated. All patients had previously
      been treated with surgery, concurrent radiotherapy and temozolomide, and post
      radiotherapy temozolomide. Bevacizumab (with or without lomustine) was
      administered to all patients at first recurrence. Patients were treated with
      nivolumab only (3 mg/kg) once every 2 weeks at second recurrence. One cycle of
      nivolumab was defined as 2 treatments. Neurological evaluation was performed bi
      weekly and neuroradiographic assessment every 4 weeks. A total of 37 treatment
      cycles (median 2) were administered of nivolumab in which there were 14 Grade 2
      adverse events (AEs) and Grade 3 AEs in two patients. No Grade 4 or 5 AEs were
      seen. Following 1 month of nivolumab, seven patients demonstrated progressive
      disease and discontinued therapy. No patient demonstrated a response though nine
      patients demonstrated neuroradiographic stable response. Survival in the entire
      cohort ranged from 2 to 6 months with a median of 3.5 months (CI 2.8, 4.2).
      Median and 6-month PFS at 6 months was 2.0 months (range 1-5 months; CI 1.3, 2.7)
      and 0% respectively. Nivolumab salvage therapy demonstrated no survival advantage
      in patients with recurrent bevacizumab refractory GBM emphasizing a continued
      unmet need in neuro-oncology.

PMID- 28500560
TI  - Radiation necrosis with stereotactic radiosurgery combined with CTLA-4 blockade
      and PD-1 inhibition for treatment of intracranial disease in metastatic melanoma.
AB  - Immune checkpoint inhibitors have demonstrated remarkable benefits in cancer
      patients. However, concern regarding toxicity in the setting of stereotactic
      radiosurgery (SRS) is often raised. In this study, we characterize radiation
      necrosis (RN) following immunotherapy and SRS. Melanoma patients treated with SRS
      and anti-CTLA-4 and/or anti-PD-1 at our institution from January 2006 to December
      2015 were retrospectively reviewed. Overall survival (OS) and time to RN were
      assessed using Kaplan-Meier analysis. Logistic regression and Cox proportional
      hazards analyses were performed to identify predictors of radiation necrosis-free
      survival (RNFS) and RN risk. One-hundred thirty-seven patients with 1094 treated
      lesions over 296 SRS sessions were analyzed. Median follow-up was 9.8 months from
      SRS. Rate of RN was 27% of patients with median time to RN of 6 months. Median OS
      from SRS treatment was 16.9 months. RNFS at 6 months, 1 and 2 years was 92.7,
      83.0, and 81.2%. Treatment with chemotherapy within 6 months of SRS was
      associated with worse RNFS at 1 year (78.4 vs. 87.5%, p = 0.017). On multivariate
      analysis, chemotherapy within 6 months and increased number of lesions treated
      were predictive of increased RN risk (HR 2.20, 95% CI 1.22-3.97, p = 0.009; HR
      1.09, 95% CI 1.03-1.15, p = 0.002), whereas immunotherapy type and targeted
      therapy were not predictive. Median target volume of lesions that developed RN
      was greater than that of lesions that did not (p < 0.001). Concurrent treatment
      with chemotherapy, larger size and number of lesions treated were predictive of
      RN. Immunotherapy type and timing proximity to SRS were not associated with RN
      risk.

PMID- 28500561
TI  - Study of beta-catenin and BRAF alterations in adamantinomatous and papillary
      craniopharyngiomas: mutation analysis with immunohistochemical correlation in 54
      cases.
AB  - Craniopharyngiomas (CP) are rare benign epithelial tumors, with two histological
      variants, namely the adamantinomatous variant (ACP) and the rarer papillary
      variant (PCP). They are locally infiltrative and surgically challenging tumors
      with severe long term morbidity. CTNNB1 mutations with beta-catenin
      immunopositivity and BRAFV600E mutations with anti-VE immunopositivity have been
      recently described in ACPs and PCPs respectively. We aimed to study BRAF and
      CTNNB1 gene mutations in CPs operated at our institute, and correlate it with
      clinicopathological parameters including histopathology and immunohistochemistry
      (IHC) for proteins VE-1 and beta-catenin. A total of 54 CPs diagnosed over 3-year
      duration were included. IHC for beta-catenin and VE-1 proteins, and Sanger
      sequencing for CTNNB1 (exon 3) and BRAF (exon 15) genes were performed. CTNNB1
      mutations were identified in 63% (27/43) of ACPs while nuclear immunopositivity
      for beta-catenin was observed in 79% (34/43) of them. Seven ACPs showed beta
      catenin immunopositivity in the absence of mutations. BRAFV600E (p.Val600Glu)
      mutations were observed in 57% of PCPs (4/7), while cytoplasmic immunopositivity
      for anti-VE1 antibody was observed only in 43% of PCPs (3/7), all of which also
      harboured BRAFV600E mutations. The mutations and IHC staining patterns of ACPs
      and PCPs were non-overlapping. Four cases with uncertain histological pattern
      could be subcategorised into specific variants only following mutation
      analysis/IHC. The identification of hallmark molecular signatures in the two CP
      variants holds promise for alternate improved treatment modalities, emphasizing
      the need for sub-categorization in routine histopathology reporting. IHC for beta
      catenin and targeted sequencing for BRAFV600E serve as useful adjuncts.

PMID- 28500563
TI  - Human Sexual Orientation: The Importance of Evidentiary Convergence.

PMID- 28500562
TI  - Epithelial growth factor receptor expression influences 5-ALA induced
      glioblastoma fluorescence.
AB  - The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a
      determining impact in high-grade glioma and glioblastoma surgery. Yet the
      intensity of the 5-ALA induced fluorescence may vary within the tumor. We aimed
      to correlate 5-ALA induced fluorescence with the expression of epithelial growth
      factor receptor (EGFR) and its constitutively active version EGFRvIII in
      different glioblastoma (GBM) cell lines. To elucidate the role of EGFR in the
      metabolism of 5-ALA in GBM cell lines with variable EGFR expression status, we
      analyzed the activation of EGFR by its primary ligand EGF, and its downstream
      effect on Heme oxygenase-1 (HO-1), a key enzyme regulating the metabolism of
      Protoporphyrin IX (PpIX), the fluorescent metabolite of 5-ALA. Effects of direct
      pharmacological inhibition by Tin(IV)-Protoporphyrin (SnPP) or gene knockdown by
      small interfering RNA (siRNA) on HO-1 enzyme were analyzed in respect to 5-ALA
      induced fluorescence. Furthermore, inhibition of EGFR by Gefitinib was tested. A
      significant difference in 5-ALA induced fluorescence was obtained in U87MG (low
      EGFR expression) and LN229EGFR cells (EGFR overexpression) compared to BS153
      (EGFR overexpression/EGFRvIII+). Treatment of U87MG and LN229EGFR cells with EGF
      significantly reduced cellular fluorescence, by promoting HO-1 transcription and
      expression in a concentration-dependent manner. This effect could be reversed by
      EGFR-specific siRNA treatment, which reduced protein expression of about 80% in
      U87MG. Remarkably, inhibition of HO-1 activity by SnPP or reduction of HO-1
      protein levels by siHO-1 treatment restored fluorescence in all cell lines,
      independently of EGFR quantitative and qualitative expression. Gefitinib
      treatment was able to restore fluorescence after EGF stimulation in U87MG cells
      but not in BS153 cells, overexpressing EGFR/EGFRvIII. In GBM cell lines, 5-ALA
      induced fluorescence is variable and influenced by EGF-induced downstream
      activation of HO-1. HO-1 protein expression was identified as a negative
      regulator of 5-ALA induced fluorescence in GBM cells. We further propose that co
      expression of EGFRvIII but not quantitative EGFR expression influence HO-1
      activity and therefore cellular fluorescence.

PMID- 28500566
TI  - An update on addressing important peripheral nerve problems: challenges and
      potential solutions.
AB  - From time to time it is thoughtful and productive to review a medical field and
      reflect upon what are the major issues that need to be addressed and what is
      being done to do so. This review article is not meant to be all-inclusive but
      rather focuses on four evolving areas in the field of peripheral nerve disorders
      and treatments: (1) nerve surgery under ultrasound guidance using a new ultra
      minimally invasive thread technique; (2) evolving magnetic resonance imaging
      (MRI) and ultrasound imaging techniques that are helping to both diagnose and
      treat a variety of peripheral nerve problems including entrapment neuropathies,
      traumatic nerve injuries, and masses arising from nerves; (3) promoting recovery
      after nerve injury using electrical stimulation; and (4) developing animal models
      to reproduce a severe nerve injury (neurotmetic grade in continuity) that
      requires a surgical intervention and repair. In each area we first describe the
      current challenges and then discuss new and emerging techniques and approaches.
      It is our hope that this article will bring added attention and resources to help
      better address peripheral nerve problems that remain a challenge for both
      patients and physicians.

PMID- 28500567
TI  - Bi-nostril transseptal endoscopic approach to the sphenoidal gate. A new
      technique.
AB  - BACKGROUND: There are multiple approaches to reach the sellar region using
      microscope or endoscope, which are the old sublabial, with its post-operative
      morbidities, or the uni-nostril transseptal, which has a limited working field.
      Another technique is the direct transnasal, which is associated with tissue
      sacrifice, and lastly the bi-nostril (one side transseptal-other side
      transnasal), aiming to preserve one of the septal flaps. METHOD: We have 27 case
      studies using a new technique in which we access the sphenoid endoscopicaly
      through the nasal septum from both nostrils under the mucoperichondrial
      periosteal flap. CONCLUSION: This new technique provides easy way of wide
      exposure to the sphenoidal gate, with easier closure of the operative field.

PMID- 28500565
TI  - Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus
      Erythematosus.
AB  - Biases in the distribution and phenotype of T, B, and antigen-presenting cell
      populations are strongly connected to mechanisms of disease development in mouse
      models of systemic lupus erythematosus (SLE). Here, we describe longitudinal
      changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and
      spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic
      mice), and how they integrate in our present understanding of the pathogenesis of
      the disease. In particular, we focus on (autoreactive) T cell activation patterns
      in lupus-prone mice. Break of T cell tolerance to chromatin constituents (histone
      peptides) is key to the development of the disease and is related to T cell
      intrinsic defects, contributed by genetic susceptibility factors and by extrinsic
      amplificatory mechanisms, in particular over-stimulation by antigen-presenting
      cells. We also describe shifts in B cell sub-populations, going from skewed
      immature B cell populations as an indication of disturbed central and peripheral
      tolerance checkpoints, to enriched long-lived plasma cells, which are key to
      persistent autoantibody production in the disease. B cell activation mechanisms
      in SLE are both T cell-dependent (break of tolerance and production of specific
      autoantibodies) and -independent (polyclonal B cell activation, production of
      autoantibodies by long-lived plasma cells). By providing a comprehensive
      evaluation of B and T cell surface markers in two major mouse models of SLE and a
      description of their changes before and after disease onset, this review
      illustrates how the study of lymphoid cell phenotype delivers key information
      regarding pathogenic pathways and supplies tools to assess the beneficial effects
      of novel therapeutic interventions.

PMID- 28500564
TI  - Calcium Signaling: From Normal B Cell Development to Tolerance Breakdown and
      Autoimmunity.
AB  - Maintenance of self-tolerance of auto-reactive lymphocytes is a fundamental
      mechanism to prevent the onset of autoimmune diseases. Deciphering the mechanisms
      involved in the deregulations leading to tolerance disruption and autoimmunity is
      still a major area of interest to identify new therapeutic targets and options.
      Ca2+ signaling plays a major role in B cell normal development and is therefore
      finely tuned by B cell receptor (BCR)-dependent and independent pathways.
      Developmental changes in the characteristics of BCR-dependent Ca2+ signals as
      well as the modulation of basal intracellular concentration ([Ca2+]i) contribute
      strongly to self-tolerance maintaining mechanisms responsible for the physical or
      functional elimination of autoreactive B cells such as clonal deletion, receptor
      editing, and anergy. Implication of Ca2+ signals in B tolerance mechanisms mainly
      occurs through the specific activation of transcriptional programs depending on
      the amplitude, shape, and duration of Ca2+ signals. A large number of studies
      reported Ca2+ signaling defects in autoimmune pathology such as systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjogren's syndrome
      (pSS). However, the precise nature of the molecular events responsible for these
      deregulations is not fully understood. Moreover, the demonstration of a direct
      correlation between Ca2+ signaling defects and tolerance disruption is still
      lacking. The recent identification of proteins involved in B cell Ca2+ signals
      such as ORAI, stromal interaction molecule and transient receptor potential is
      opening new horizons for understanding Ca2+ signaling defects observed in
      autoimmune diseases and for proposing potentially new therapeutic solutions. This
      review aims to present an overview of the developmental evolution of BCR
      dependent Ca2+ signaling and to place this signaling pathway in the context of
      mechanisms involved in tolerance maintenance and breakdown.

PMID- 28500568
TI  - Female Sex Pheromone of the Cone Moth, Dioryctria mendacella: Investigation of
      Synergism between Type I and Type II Pheromone Components.
AB  - Polyunsaturated hydrocarbons (Type II pheromone components) have been reported to
      be synergists for unsaturated acetates, alcohols or aldehydes (Type I components)
      in the sex pheromones of several species of Lepidoptera. However, there is some
      debate over whether the active components are the hydrocarbons themselves or more
      volatile degradation products. Extracts of pheromone glands of adult females of
      the cone moth, Dioryctria mendacella (Lepidoptera: Pyralidae), contain (Z,E)-9,11
      tetradecadienyl acetate (ZE9,11-14:Ac) and at least ten times as much (Z,Z,Z,Z,Z)
      3,6,9,12,15-pentacosapentaene (ZZZZZ3,6,9,12,15-25:H). The former elicits a
      strong electroantennogram response from males while no response could be recorded
      to the latter. In field trapping tests, both compounds were individually
      unattractive to male D. mendacella moths, but blends of the two compounds
      containing at least a 10:1 ratio of ZZZZZ3,6,9,12,15-25:H : ZE9,11-14:Ac were
      highly attractive. The relatively involatile hydrocarbon was shown to be released
      from the dispensers used and no significant degradation could be detected.
      Furthermore, blends of ZE9,11-14:Ac and analogs of ZZZZZ3,6,9,12,15-25:H with
      fewer carbons and/or double bonds that might be expected to produce similar
      degradation products to ZZZZZ3,6,9,12,15-25:H were unattractive. This indicated a
      specific response to the hydrocarbon itself, further substantiated by the
      observation that related hydrocarbons did not interfere with the activity of
      ZZZZZ3,6,9,12,15-25:H. Thus a three-step conversion of fish oil was used to
      produce a blend of unsaturated hydrocarbons containing ZZZZZ3,6,9,12,15-25:H as
      the major component, albeit only 30% of the total, and a blend of this material
      with ZE9,11-14:Ac was as attractive to male D. mendacella moths as blends with an
      equivalent amount of the purified material. This mixture of unsaturated
      hydrocarbons is much cheaper to produce than the pure pentaene, and may be useful
      in lures for other species using these compounds. Dioryctria mendacella is a
      major constraint to production of edible pine kernels throughout the
      Mediterranean region. Pheromone traps will provide a means to improve monitoring
      of seasonal flight patterns and changes in population abundance of this pest.

PMID- 28500569
TI  - Comparison of the Chemical Compositions of the Cuticle and Dufour's Gland of Two
      Solitary Bee Species from Laboratory and Field Conditions.
AB  - Species-specific biochemistry, morphology, and function of the Dufour's gland
      have been investigated for social bees and some non-social bee families. Most of
      the solitary bees previously examined are ground-nesting bees that use Dufour's
      gland secretions to line brood chambers. This study examines the chemistry of the
      cuticle and Dufour's gland of cavity-nesting Megachile rotundata and Osmia
      lignaria, which are species managed for crop pollination. Glandular and cuticular
      lipid compositions were characterized and compared to each other and according to
      the nesting experience of adult females. Major lipid classes found were
      hydrocarbons, free fatty acids, and wax esters. Many components were common to
      the cuticle and Dufour's glands of each species, yet not identical in number or
      relative composition. Wax esters and fatty acids were more prevalent in Dufour's
      glands of M. rotundata than on cuticles. Wax esters were more abundant on
      cuticles of O. lignaria than in Dufour's glands. In both species, fatty acids
      were more prevalent in glands of field-collected females compared to any other
      sample type. Chemical profiles of cuticles and glands were distinct from each
      other, and, for O. lignaria, profiles of laboratory-maintained bees could be
      distinguished from those of field-collected bees. Comparison of percentiles of
      individual components of cuticular and glandular profiles of the same bee showed
      that the proportions of some cuticular components were predictive of the
      proportion of the same glandular components, especially for nesting females.
      Lastly, evidence suggested that Dufour's gland is the major source of nest
      marking substances in M. rotundata, but evidence for this role in O. lignaria was
      less conclusive.

PMID- 28500570
TI  - Narrow-band imaging can increase the visibility of fibrin caps after bleeding of
      esophageal varices: a case with extensive esophageal candidiasis.
AB  - A 58-year-old man with hepatitis B cirrhosis noticed black stools and underwent
      an endoscopy at a community hospital. The presence of esophageal varices (EVs)
      was confirmed, but the bleeding point was not found. He was referred to our
      institution and underwent a second endoscopy. Extensive white patches of
      esophageal candidiasis were visible on endoscopy by white-light imaging (WLI),
      but it was difficult to find the fibrin cap of the EVs. This was easier under
      narrow-band imaging (NBI), however, as the color turned red from absorption by
      hemoglobin adhered to it. We retrospectively measured the color differences (CD)
      between the fibrin cap and the surrounding mucosa 10 times using the CIE (L*a*b*)
      color space method. The median value of CD increased after NBI (13.9 -> 43.0, p <
      0.001), with increased visibility. However, the median CD between the white patch
      and surrounding mucosa decreased after NBI (44.8 -> 30.3, p < 0.001). The fibrin
      cap was paler than the white patch of candidiasis, but the increased visibility
      of the fibrin cap by NBI enabled it to be found more easily. This is the first
      report of a case in which NBI was helpful in locating a fibrin cap of EVs.

PMID- 28500574
TI  - Tissue Engineering-Bridging the Gap.

PMID- 28500571
TI  - Associations between illness duration and health-related quality of life in
      specified mental and physical chronic health conditions: results from a
      population-based survey.
AB  - PURPOSE: We compared health-related quality of life (HRQOL) in incident (<=1 year
      since diagnosis), mid-term (>1-5 years since diagnosis), and long-term (>5 years
      since diagnosis) cases of mental and physical chronic illness with the general
      population and assessed the modifying effects of age and gender on the
      association between HRQOL and illness duration. METHODS: Data from the 2007
      Australian National Health and Mental Wellbeing Survey were used. HRQOL was
      captured by the Assessment of Quality of Life Scale 4D. Multivariable linear
      regression analyses compared HRQOL of individuals with different duration of
      illnesses with those who did not have the condition of interest. RESULTS: The
      8841 survey respondents were aged 16-85 years (median 43 years, 50.3% female).
      For the overall sample, worse HRQOL was associated with incident (P = 0.049) and
      mid-term (P = 0.036) stroke and long-term depression (P < 0.001) and anxiety (P =
      0.001). Age had moderating effect on the associations between HRQOL and duration
      of asthma (P < 0.001), arthritis (P = 0.001), diabetes (P = 0.004), stroke (P =
      0.009), depression (P < 0.001), bipolar disorder (P < 0.001), and anxiety (P <
      0.001), but not heart disease (P = 0.102). In older ages, the greatest loss in
      HRQOL was associated with incident asthma, depression, and bipolar disorder. In
      younger ages, the greatest loss in HRQOL was associated with arthritis (any
      duration) and incident diabetes and anxiety. Additionally, gender moderated the
      association between HRQOL and arthritis, with worse HRQOL among men with incident
      arthritis (P = 0.047). CONCLUSIONS: Loss of HRQOL associated with longer duration
      of chronic illness is most apparent in stroke and mental illness and differs
      between age groups.

PMID- 28500572
TI  - Methods and impact of engagement in research, from theory to practice and back
      again: early findings from the Patient-Centered Outcomes Research Institute.
AB  - PURPOSE: Since 2012, PCORI has been funding patient-centered comparative
      effectiveness research with a requirement for engaging patients and other
      stakeholders in the research, a requirement that is unique among the US funders
      of clinical research. This paper presents PCORI's evaluation framework for
      assessing the short- and long-term impacts of engagement; describes engagement in
      PCORI projects (types of stakeholders engaged, when in the research process they
      are engaged and how they are engaged, contributions of their engagement); and
      identifies the effects of engagement on study design, processes, and outcomes
      selection, as reported by both PCORI-funded investigators and patient and other
      stakeholder research partners. METHODS: Detailed quantitative and qualitative
      information collected annually from investigators and their partners was analyzed
      via descriptive statistics and cross-sectional qualitative content and thematic
      analysis, and compared against the outcomes expected from the evaluation
      framework and its underlying conceptual model. RESULTS: The data support the role
      of engaged research partners in refinements to the research questions, selection
      of interventions to compare, choice of study outcomes and how they are measured,
      contributions to strategies for recruitment, and ensuring studies are patient
      centered. CONCLUSIONS: The evaluation framework and the underlying conceptual
      model are supported by results to date. PCORI will continue to assess the effects
      of engagement as the funded projects progress toward completion, dissemination,
      and uptake into clinical decision making.

PMID- 28500575
TI  - Salt and Blood Pressure: Cutting Through the Scientific Fog.

PMID- 28500573
TI  - Brief Report: Contrasting Profiles of Everyday Executive Functioning in Smith
      Magenis Syndrome and Down Syndrome.
AB  - Everyday executive function (EF) was examined in Smith-Magenis syndrome (SMS),
      associated with high risk of behaviour disorder, and Down syndrome (DS),
      associated with relatively low risk of behaviour disorder. Caregivers of 13
      children with SMS and 17 with DS rated everyday EF using the Behavioral Rating
      Inventory of Executive Functioning-Preschool. Greater everyday EF deficits
      relative to adaptive ability were evident in SMS than in DS. The SMS profile of
      everyday EF abilities was relatively uniform; in DS emotional control strengths
      and working memory weaknesses were evident. Findings implicate broad everyday EF
      difficulties in SMS compared to DS, corresponding with increased rates of
      behaviour disorder in SMS. Findings further suggest that everyday EF profiles
      may, in part, be syndrome related.

PMID- 28500576
TI  - 66th Annual Scientific Sessions of the American College of Cardiology: 17-19
      March 2017; Washington, DC, USA.

PMID- 28500577
TI  - Pectin Esterification Degree in the Bioavailability of Non-heme Iron in Women.
AB  - Pectins are a type of soluble fiber present in natural and processed foods.
      Evidence regarding the effect of esterification degree of pectins on iron
      absorption in humans is scarce. In the present study, the effect of pectins with
      different degrees of esterification on non-heme iron absorption in women was
      evaluated. A controlled experimental study was conducted with block design,
      involving 13 apparently healthy, adult women. Each subject received 5 mg Fe
      (FeSO4) without pectin (control) or accompanied by 5 g citrus pectin, two with a
      low degree of esterification (27 and 36%), and one with a high degree of
      esterification (67 to 73%), each on different days. Each day, the 5 mg Fe doses
      were marked with radioactive 59Fe or 55Fe. Radioactivity incorporated into
      erythrocytes was determined in blood samples 14 days after the marked Fe doses
      were consumed. On days 18 and 36 of study, 30 and 20 mL blood samples were
      obtained, respectively, and blood sample radioactivity incorporated into
      erythrocytes was determined. Body iron status was determined from blood taken on
      day 18. Whole body blood volume was estimated for calculate iron bioavailability;
      it was assumed that 80% of absorbed radioactivity was incorporated into the Hb.
      All women participants signed an informed consent of participation at baseline.
      Iron bioavailability (mean geometric +/-1 SD) alone (control) was 18.2% (12.3
      27.1%), iron + pectin27 was 17.2% (10.2-29.2%), iron + pectin36 was 15.3% (9.5
      24.6%), and iron + pectin67 was 19.5% (10.0-38.0%). No statistically significant
      differences between iron bioavailability (repeated measures ANOVA, p = 0.22) were
      observed. Pectin esterification degree does not influence the bioavailability of
      non-heme iron in women.

PMID- 28500578
TI  - The Relationship Between Copper, Iron, and Selenium Levels and Alzheimer Disease.
AB  - This study aimed to evaluate the concentrations of copper, iron, and selenium in
      elderly people with Alzheimer disease (AD), comparing the same parameters in a
      paired group of healthy people, in order to verify if the amount of these metals
      may influence the cognitive impairment progression. Patients' cognitive
      impairment was evaluated by Clinical Dementia Rating (CDR). The elementary
      quantification of erythrocytes was performed by inductively coupled plasma mass
      spectrometry technique. The statistical analyses were carried out by SPSS
      software 20.0 version, employing Shapiro-Wilk, Wilcoxon, Kruskall-Wallis, and
      Spearman correlation tests, considering significant results of p < 0.05. The
      sample was composed of 34% (n = 11) of women and 66% (n = 21) of men in each
      group. The AD group was characterized by a higher concentration of copper (p <
      0.0001) and iron (p < 0.0001); however, there is no significant difference in
      selenium level. The analyses of the metal levels in different stages of AD were
      not significant in CDR-1, however in CDR-2 and CDR-3, elevated levels of copper
      and iron were observed; in CDR-3 patients, the level of selenium was lower (p <
      0.008) compared to that of healthy controls. Patients with Alzheimer disease
      studied present increase in biometal blood levels, especially of copper and iron,
      and such increase can be different according to the disease stage and can cause
      more impairment cognitive functions in AD.

PMID- 28500581
TI  - John M. Hayes (1940-2017).
AB  - ?.

PMID- 28500579
TI  - Robotic repair of a right-sided Bochdalek hernia: a case report and literature
      review.
AB  - BACKGROUND: Bochdalek hernias (BHs) are usually diagnosed in the neonatal period,
      occurring in 1/2200-1/12,500 live births. There are few reported cases of BHs in
      adults. Robotic repair has not been described in current literature as opposed to
      the laparoscopic approach. Here we present a case of an adult with clinical signs
      of bowel obstruction secondary to a BH which was repaired using a robotic
      approach. CASE REPORT: A 74-year-old gentleman with past medical history of
      benign prostatic hyperplasia presented to the emergency department with a 1-week
      history of nausea, vomiting, diarrhea, and decline in appetite. Computed
      tomography (CT) imaging of the chest and abdomen revealed elevation of the right
      hemidiaphragm and evidence of small bowel obstruction. The patient was managed
      conservatively with nasogastric tube placement and bowel rest. He underwent
      colonoscopy which could not be completed secondary to a transverse colon
      stricture which was confirmed by barium enema. Upon repeat CT imaging, the
      patient was found to have herniated colon through a right-sided diaphragmatic
      hernia which caused colonic narrowing. The patient's intestinal obstruction
      improved clinically with continued conservative management and he underwent
      robotic repair of a right posterior diaphragmatic hernia. The hernia defect was
      closed with interrupted figure of eight Ethibond sutures. A right-sided chest
      tube was placed. Intraoperatively, the herniated proximal transverse colon was
      noted to be ischemic and a right hemicolectomy was performed. He recovered well
      and was discharged home on postoperative day 5. CONCLUSION: Congenital
      diaphragmatic hernias usually present in the neonatal period and are rare in
      adults. Operative repair is recommended and laparoscopic repair has been
      described. Based on the existing literature regarding laparoscopic repair and the
      current case report, robotic repair also appears to be a viable and safe option.

PMID- 28500580
TI  - Is right colectomy a complete learning procedure for a robotic surgical program?
AB  - This study analyses the utility of right colectomy as a learning procedure at the
      beginning of a robotic surgical program. The hypothesis is that right colectomy
      contains all the technical steps necessary to acquire basic abilities in robotics
      surgery. The first 23 consecutive robotic right colectomy performed at the
      beginning of a robotic program were analysed. All surgical times were recorded in
      the operating room and second checked on a dedicated video-database. Specific
      robotic times were analysed using CUSUM method to evaluate the learning curve.
      CUSUM-derived learning phases were compared. Fourteen males and nine females with
      a mean age of 68.7 (46-84) underwent robotic right colectomy. The mean overall
      time was 265.3 min (180-320 min), docking time was 7 min (5-12 min), console time
      was 205.9 min (145-260 min), and anastomotic time was 43.6 (25-60 min). CUSUM
      analyses identified two learning phases: "starting phase" and "consolidation
      phase". Interphase comparison confirmed the significant (p < 0.05) differences
      between the two phases. Robotic technology facilitates the training process in
      minimally invasive colorectal surgery. At the beginning of the learning curve,
      right colectomy could represent a complete procedure to be proficient in robotic
      colorectal surgery.

PMID- 28500582
TI  - How Hot are Your Ions Really? A Threshold Collision-Induced Dissociation Study of
      Substituted Benzylpyridinium "Thermometer" Ions.
AB  - The first absolute experimental bond dissociation energies (BDEs) for the main
      heterolytic bond cleavages of four benzylpyridinium "thermometer" ions are
      measured using threshold collision-induced dissociation in a guided ion beam
      tandem mass spectrometer. In this experiment, substituted benzylpyridinium ions
      are introduced into the apparatus using an electrospray ionization source,
      thermalized, and collided with Xe at varied kinetic energies to determine
      absolute cross-sections for these reactions. Various effects are accounted for,
      including kinetic shifts, multiple collisions, and internal and kinetic energy
      distributions. These experimentally measured 0 K BDEs are compared with
      computationally predicted values at the B3LYP-GD3BJ, M06-GD3, and MP2(full)
      levels of theory with a 6-311+G(2d,2p) basis set using vibrational frequencies
      and geometries determined at the B3LYP/6-311+G(d,p) level. Additional
      dissociation pathways are observed for nitrobenzylpyridinium experimentally and
      investigated using these same levels of theory. Experimental BDEs are also
      compared against values in the literature at the AM1, HF, B3LYP, B3P86, and
      CCSD(T) levels of theory. Of the calculated values obtained in this work, the
      MP2(full) level of theory with counterpoise corrections best reproduces the
      experimental results, as do the similar literature CCSD(T) values. Lastly, the
      survival yield method is used to determine the characteristic temperature (Tchar)
      of the electrospray source prior to the thermalization region and to confirm
      efficient thermalization. Graphical Abstract ?.

PMID- 28500583
TI  - Laser-Induced Acoustic Desorption/Electron Ionization of Amino Acids and Small
      Peptides.
AB  - Laser-induced acoustic desorption (LIAD) allows for desorption of neutral
      nonvolatile compounds independent of their volatility or thermal stability. Many
      different ionization methods have been coupled with LIAD. Hence, this setup
      provides a better control over the types of ions formed than other mass
      spectrometry evaporation/ionization methods commonly used to characterize
      biomolecules, such as ESI or MALDI. In this study, the utility of LIAD coupled
      with electron ionization (EI) was tested for the analysis of common amino acids
      with no derivatization. The results compared favorably with previously reported
      EI mass spectra obtained using thermal desorption/EI. Further, LIAD/EI mass
      spectra collected for hydrochloride salts of two amino acids were found to be
      similar to those measured for the neutral amino acids with the exception of the
      appearance of an HCl+? ion. However, the hydrochloride salt of arginine showed a
      distinctly different LIAD/EI mass spectrum than the previously published
      literature EI mass spectrum, likely due to its highly basic side chain that makes
      a specific zwitterionic form particularly favorable. Finally, EI mass spectra
      were measured for seven small peptides, including di-, tri-, and tetrapeptides.
      These mass spectra show a variety of ion types. However, an type ions are
      prevalent. Also, electron-induced dissociation (EID) of protonated peptides has
      been reported to form primarily an type ions. In addition, the loss of small
      neutral molecules and side-chain cleavages were observed that are reminiscent of
      other high-energy fragmentation methods, such as EID. Finally, the isomeric
      dipeptides LG and IG were found to produce drastically different EI mass spectra,
      thus allowing differentiation of the leucine and isoleucine amino acids in these
      dipeptides. Graphical Abstract ?.

PMID- 28500584
TI  - Specific Interactions of Antitumor Metallocenes with Deoxydinucleoside
      Monophosphates.
AB  - Bent metallocenes Cp2MCl2 (M = Ti, V, Nb, Mo) are known to exhibit cytotoxic
      activity against a variety of cancer types. Though the mechanism of action is not
      fully understood yet, the accumulation of the metal ions in the nucleus points
      towards DNA as one of the primary targets. A set of eight deoxydinucleoside
      monophosphates was used to study the adduct yields with metallocenes and
      cisplatin. The binding affinities are reflected by the relative intensities of
      the adducts and were found to follow the order of Pt > V > Ti > Mo (no adducts
      were detected with Nb). High-resolution tandem mass spectrometry was applied to
      locate the binding patterns in the deoxydinucleoside monophosphates. Whereas
      cisplatin binds to the soft nitrogen atoms in the purine nucleobases, the
      metallocenes additionally interact with the hard phosphate oxygen, which is in
      good agreement with the hard and soft (Lewis) acids and bases (HSAB) concept.
      However, the binding specificities were found to be unique for each metallocene.
      The hard Lewis acids titanium and vanadium predominantly bind to the deprotonated
      phosphate oxygen, whereas molybdenum, an intermediate Lewis acid, preferentially
      interacts with the nucleobases. Nucleobases comprise alternative binding sites
      for titanium and vanadium, presumably oxygen atoms for the first and nitrogen
      atoms for the latter. In summary, the intrinsic binding behavior of the different
      metallodrugs is reflected by the gas-phase dissociation of the adducts.
      Consequently, MS/MS can provide insights into therapeutically relevant
      interactions between metallodrugs and their cellular targets. Graphical Abstract
      ?.

PMID- 28500586
TI  - Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA
      Treatments Awaiting Liver Transplantation.

PMID- 28500585
TI  - Systematic review and meta-analysis of complications and mortality of veno-venous
      extracorporeal membrane oxygenation for refractory acute respiratory distress
      syndrome.
AB  - Veno-venous extracorporeal membrane oxygenation (ECMO) for refractory acute
      respiratory distress syndrome (ARDS) is a rapidly expanding technique. We
      performed a systematic review and meta-analysis of the most recent literature to
      analyse complications and hospital mortality associated with this technique.
      Using the PRISMA guidelines for systematic reviews and meta-analysis, MEDLINE and
      EMBASE were systematically searched for studies reporting complications and
      hospital mortality of adult patients receiving veno-venous ECMO for severe and
      refractory ARDS. Studies were screened for low bias risk and assessed for study
      size effect. Meta-analytic pooled estimation of study variables was performed
      using a weighted random effects model for study size. Models with potential
      moderators were explored using random effects meta-regression. Twelve studies
      fulfilled inclusion criteria, representing a population of 1042 patients with
      refractory ARDS. Pooled mortality at hospital discharge was 37.7% (CI 95% = 31.8
      44.1; I 2 = 74.2%). Adjusted mortality including one imputable missing study was
      39.3% (CI 95% = 33.1-45.9). Meta-regression model combining patient age, year of
      study realization, mechanical ventilation (MV) days and prone positioning before
      veno-venous ECMO was associated with hospital mortality (p < 0.001; R 2 = 0.80).
      Patient age (b = 0.053; p = 0.01) and maximum cannula size during treatment (b = 
      0.075; p = 0.008) were also independently associated with mortality. Studies
      reporting H1N1 patients presented inferior hospital mortality (24.8 vs 40.6%; p =
      0.027). Complication rate was 40.2% (CI 95% = 25.8-56.5), being bleeding the most
      frequent 29.3% (CI 95% = 20.8-39.6). Mortality due to complications was 6.9% (CI
      95% = 4.1-11.2). Mechanical complications were present in 10.9% of cases (CI 95%
      = 4.7-23.5), being oxygenator failure the most prevalent (12.8%; CI 95% = 7.1
      21.7). Despite initial severity, significant portion of patients treated with
      veno-venous ECMO survive hospital discharge. Patient age, H1N1-ARDS and cannula
      size are independently associated with hospital mortality. Combined effect of
      patient age, year of study realization, MV days and prone positioning before veno
      venous ECMO influence patient outcome, and although medical complications are
      frequent, their impact on mortality is limited.

PMID- 28500587
TI  - Insights into the Pathogenesis of Pancreatic Cystic Neoplasms.
AB  - With the current epidemic of diagnosed pancreatic cystic neoplasms on the rise, a
      substantial amount of work has been done to unravel their biology, thus leading
      to implications on clinical decision making. Recent genetic profiling of resected
      human specimens has identified alterations in signaling pathways involving KRAS
      and GNAS signaling as early events in the pathogenesis of intraductal pancreatic
      mucinous neoplasms. Progressively, mutations in genes such as TP53, SMAD4, RNF43,
      and others are thought to characterize invasive and advanced lesions. The role of
      inflammation in fueling the growth and transformation of these cysts has also
      begun to be studied with greater interest. A number of promising clinical studies
      have attempted to integrate these genetic insights into classifying these cysts
      and treating patients. We have reviewed existing literature on similar lines
      besides commenting on some useful animal models that recapitulate molecular and
      phenotypic progression of these cysts.

PMID- 28500588
TI  - Sun Should Not Rise and Set on a Case of Acute Intestinal Obstruction.

PMID- 28500589
TI  - Prospective Analysis of Minor Adverse Events After Colon Polypectomy.
AB  - BACKGROUND: The risks of minor adverse events (MAEs) such as abdominal pain and
      bloating after colon polypectomy (CP) are less clearly documented than major
      adverse events. However, these complications may cause significant discomfort
      during the performance of normal activities. We aimed to estimate the incidence
      of MAE, associated risk factors, and healthcare resource utilization after CP.
      METHODS: Patients who underwent CP were prospectively enrolled in this study.
      Trained nurses contacted patients by telephone at 7 and 30 days after the CP and
      administered a standardized questionnaire to obtain information regarding the
      development of complications. MAEs were defined as any discomfort the patient
      experienced after CP excluding major bleeding, perforation, and post-polypectomy
      coagulation syndrome. RESULTS: Among a total of 2716 patients, 2253 patients
      completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%)
      before day 7, among which the most common were abdominal pain (4.5%), rectal
      bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267
      patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio
      [OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR
      1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two
      patients (0.7%) required hospital admission, 117 patients (43.8%) were treated
      medically in the outpatient clinic, and the majority at 148 patients (55.4%)
      experienced resolution of symptoms after observation. CONCLUSIONS: The post-CP
      MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven
      postoperative days and resulted in little use of healthcare resources.

PMID- 28500590
TI  - Autolysis of Pichia pastoris induced by cold.
AB  - The production of recombinant biopharmaceutical proteins is a multi-billion
      dollar market. Protein recovery represents a major part of the production costs.
      Pichia pastoris is one of the microbial systems most used for the production of
      heterologous proteins. The use of a cold-induced promoter to express lytic
      enzymes in the yeast after the growth stage could reduce protein recovery costs.
      This study shows that a cold-shock can be applied to induce lysis of the yeast
      cells. A strain of P. pastoris was constructed in which the endogenous eng gene
      encoding a putative endo-beta-1,3-glucanase was overexpressed using the cold
      shock induced promoter of the cctalpha gene from Saccharomyces cerevisiae. In the
      transgenic P. pastoris, the expression of eng increased 3.6-fold after chilling
      the cells from 30 to 4  degrees C (cold-shock stage) followed by incubation for 6
      h (eng expression stage). The culture was heated to 30  degrees C for 6 h (ENG
      synthesis stage) and kept at 37  degrees C for 24 h (lysis stage). After this
      procedure the cell morphology changed, spheroplasts were obtained and cellular
      lysis was observed. Thus, a clone of P. pastoris was obtained, which undergoes
      autolysis after a cold-shock.

PMID- 28500591
TI  - A Brief Introduction into the Renin-Angiotensin-Aldosterone System: New and Old
      Techniques.
AB  - The renin-angiotensin-aldosterone system (RAAS) is a complex system of enzymes,
      receptors, and peptides that help to control blood pressure and fluid
      homeostasis. Techniques in studying the RAAS can be difficult due to such factors
      as peptide/enzyme stability and receptor localization. This paper gives a brief
      account of the different components of the RAAS and current methods in measuring
      each component. There is also a discussion of different methods in measuring stem
      and immune cells by flow cytometry, hypertension, atherosclerosis, oxidative
      stress, energy balance, and other RAAS-activated phenotypes. While studies on the
      RAAS have been performed for over 100 years, new techniques have allowed
      scientists to come up with new insights into this system. These techniques are
      detailed in this Methods in Molecular Biology Series and give students new to
      studying the RAAS the proper controls and technical details needed to perform
      each procedure.

PMID- 28500592
TI  - A Color Segmentation-Based Method to Quantify Atherosclerotic Lesion Compositions
      with Immunostaining.
AB  - There is an increasing recognition that atherosclerotic lesion composition,
      rather than size, is the determinant of acute events. Immunostaining is a
      commonly used method to characterize atherosclerotic lesion compositions. Here,
      we describe a color segmentation-based approach in HSI (hue, saturation, and
      intensity) color mode, which minimizes subjectivity and produces accurate and
      consistent quantifications of atherosclerotic lesion compositions.

PMID- 28500593
TI  - Assessment of Protein Carbonylation and Protein Tyrosine Phosphatase (PTP)
      Oxidation in Vascular Smooth Muscle Cells (VSMCs) Using Immunoblotting
      Approaches.
AB  - Post-translational modification of proteins, such as phosphorylation and
      oxidation, plays a major role in cellular signaling by influencing protein
      structure and function. In vascular cells, in addition to influencing
      phosphorylation, angiotensin II (Ang II) induces oxidation of proteins, important
      in redox signaling in the cardiovascular and renal systems. The present chapter
      describes immunoblotting approaches to assess irreversible protein carbonylation
      and protein tyrosine phosphatase (PTPs) oxidation status in the proteome of
      vascular smooth muscle cells (VSMC).Protein carbonylation is generally measured
      using the OxyBlotTM approach, whereby derivatization of protein carbonyl groups
      (C = O) on oxidized amino acids by dinitrophenylhydrazine (DNPH) results in the
      formation of a stable dinitrophenyl (DNP) hydrazone product. The samples are
      analyzed by SDS-PAGE and a primary antibody raised against the DNP moiety is used
      to determine levels of irreversible protein carbonylation in the sample by
      immunoblotting.Oxidation of PTPs can be evaluated using a monoclonal antibody
      against the "hyperoxidized" (SO3H) catalytic site of these enzymes. The described
      methodology offers the ability to discriminate between irreversible (SO3H) and
      reversible (SOH) PTP oxidation states. Initially, the free unmodified PTP-thiols
      (S-) are alkylated and the sample is split into two. One part is used to assess
      the PTP-SO3H form. In the other part reversibly modified PTP-thiols are first
      reduced and then hyperoxidized by pervanadate (PV). Both untreated and PV-treated
      samples are analyzed by SDS-PAGE and "hyperoxidized" PTPs are detected by
      immunoblotting. The proportion of reversibly oxidized PTP-SOH fraction is
      determined by the difference between the signals in untreated and the PV-treated
      samples.The above immunoassays provide general approaches to detect and quantify
      global levels of irreversible protein oxidation and of irreversibly/reversibly
      oxidized PTPs in any (patho)physiological context. Characterization of the global
      redox status is essential to better understand the redox-sensitive mechanisms
      underlying chronic diseases associated with oxidative stress. This is
      particularly important in systems influenced by the renin angiotensin system,
      because Ang II is a potent inducer of oxidative stress and redox signaling.

PMID- 28500594
TI  - Methods for Studying the Role of RAAS in the Modulation of Vascular Repair
      Relevant Functions of Stem/Progenitor Cells.
AB  - In recent years, previously unknown functions have been conferred to the RAAS and
      have been explored in mechanistic studies and disease models. Implication of bone
      marrow stem/progenitor cells in the cardiovascular protective or detrimental
      effects of RAAS is a prominent advancement because of the translational
      significance. Selected members of RAAS are now known to modulate migration,
      proliferation, and mobilization of bone marrow cells in response to ischemic
      insult, which are sensitive indicators of vascular repair-relevant functions. In
      this Chapter, protocols for most frequently used, in vitro, ex vivo, and in vivo
      assays to explore the potential of RAAS members to stimulate vascular repair
      relevant functions of bone marrow stem/progenitor cells of human and murine
      origin.

PMID- 28500595
TI  - Use of a Fluorescent Substrate to Measure ACE2 Activity in the Mouse Abdominal
      Aorta.
AB  - The use of fluorogenic substrates to measure enzymatic activity is widely used to
      understand function within different experimental models. ACE2 is important in
      understanding the balance between AngII and Ang-(1-7) and how this balance could
      then in turn influence hypertension or other disease outcomes. Here, we describe
      a method to measure ACE2 activity in abdominal aorta of hyperlipidemic mice under
      both saline and AngII infusion.

PMID- 28500596
TI  - Measuring Blood Pressure Using a Noninvasive Tail Cuff Method in Mice.
AB  - The renin angiotensin system (RAS) is well known for its role in regulating blood
      pressure (BP). An activated RAS contributes to elevated blood pressure and is
      evident in both human and animal models of hypertension. Drugs that target the
      classic vasoconstrictive arm of the RAS (angiotensin II/AT1 receptor signaling)
      are potent anti-hypertensive agents in clinical setting. However, the newly
      discovered angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7)/Mas receptor
      axis added new vitality to the hypertension field. Advances in genetic
      manipulation and the relative low cost made the mouse model as one of the most
      popular animal models to study hypertension. Since a reliable and accurate method
      for BP assessment is the key for such experiments, here we provide a protocol for
      BP measurement in mice using a noninvasive BP system. The CODA noninvasive BP
      system (a tail-cuff Method, Kent Scientific Corporation) enables blood pressure
      (BP) measurements in mice. This method uses a specialized volume pressure
      recording (VPR) sensor, and measures blood volume changes that are placed over
      the animal's tail. Mice do need to be restrained in specific holders and
      artificially heated to maintain normal BP.

PMID- 28500597
TI  - Blood Pressure Monitoring Using Radio Telemetry Method in Mice.
AB  - The TA11PA-C10 implantable transmitter (Data Sciences International, DSI) is
      designed to measure blood pressure (BP) and activity in freely moving laboratory
      mice. The fluid filled catheter is placed in the free flowing blood of the
      systemic artery (inserted into the left carotid artery and extended into the
      aorta), and the transmitter body is placed in a benign location for long-term
      biocompatibility. The transmitter can be used to monitor BP in mice (as small as
      17 g) under normal physiological and unrestricted conditions 24 h a day while
      remaining free from stress associated with human interaction. Thus, telemetry is
      considered the gold standard for BP monitoring in small animals such as mice.
      However, this methodology does require a good understanding of the system as well
      as appropriate training to perform the delicate transmitter implantation surgery.

PMID- 28500598
TI  - Characterization and Functional Phenotyping of Renal Immune Cells via Flow
      Cytometry.
AB  - A variety of immune cell subsets contribute to the pathogenesis of hypertension
      and associated kidney damage following inappropriate activation of the renin
      angiotensin system (RAS). These immune cell subsets often express common surface
      markers, which complicates their separation and characterization in vivo.
      Accordingly, flow cytometry has become an invaluable tool for parsing immune cell
      populations because this technique permits the simultaneous detection of up to 18
      markers on a single cell. Below we describe a process by which one can determine
      the immune cell subsets in the kidney via flow cytometry.

PMID- 28500599
TI  - Assessment of the Renin-Angiotensin System in Cellular Organelle: New Arenas for
      Study in the Mitochondria.
AB  - The renin-angiotensin system (RAS) is an important hormonal system composed of
      various protein and peptide components that contribute to blood pressure
      regulation. Although originally characterized as a circulating system, there is
      increasing evidence for the intracellular expression of RAS elements on the
      nucleus and mitochondria that may function in concert with or independent of the
      circulating system. The present chapter describes several experimental approaches
      to quantify the expression of RAS components in isolated mitochondria from the
      kidney. These approaches are intended to provide a framework to understand the
      mitochondrial RAS within a cell-free environment.

PMID- 28500600
TI  - Comprehensive Assessments of Energy Balance in Mice.
AB  - Increasing evidence supports a major role for the renin-angiotensin system (RAS)
      in energy balance physiology. The RAS exists as a circulating system but also as
      a local paracrine/autocrine signaling mechanism in target tissues including the
      gastrointestinal tract, the brain, the kidney, and distinct adipose beds. Through
      activation of various receptors in these target tissues, the RAS contributes to
      the control of food intake behavior, digestive efficiency, spontaneous physical
      activity, and aerobic and anaerobic resting metabolism. Although the assortment
      of methodologies available to assess the various aspects of energy balance can be
      daunting for an investigator new to this area, a relatively straightforward array
      of entry-level and advanced methodologies can be employed to comprehensively and
      quantitatively dissect the effects of experimental manipulations on energy
      homeostasis. Such methodologies and a simple initial workflow for the use of
      these methods are described in this chapter, including the use of metabolic
      caging systems, bomb calorimetry, body composition analyzers, respirometry
      systems, and direct calorimetry systems. Finally, a brief discussion of the
      statistical analyses of metabolic data is included.

PMID- 28500601
TI  - In Vitro Assays to Determine Smooth Muscle Cell Hypertrophy, Protein Content, and
      Fibrosis.
AB  - This chapter provides information on how to culture primary rat vascular smooth
      muscle cells and how to induce cellular changes similar to those associated with
      angiotensin II activation in vivo. We describe how to assess the cellular changes
      by determining cell size with an automated coulter cell counter to measure cell
      volume. In addition, we describe a method to assess total protein content.
      Finally, we describe a standard technique to quantify angiotensin II-induced pro
      fibrotic response using the Chondrex Sirius Red Total Collagen Detection Kit.

PMID- 28500602
TI  - A New Mouse Model for Introduction of Aortic Aneurysm by Implantation of
      Deoxycorticosterone Acetate Pellets or Aldosterone Infusion in the Presence of
      High Salt.
AB  - Dysfunction of the renin-angiotensin-aldosterone system (RAAS) has been
      implicated in the etiologies of many cardiovascular diseases, including aortic
      aneurysm. In particular, the infusion of angiotensin II (Ang II) in the
      apolipoprotein E-deficient mice (apoE-/-) and low density lipoprotein receptor
      knockout mice (LDLR-/-) to induce aortic aneurysm has been extensively used in
      the field. In contrast, whether aldosterone (Aldo), an essential component of
      RAAS and a downstream effector of Ang II, is involved in aortic aneurysm is
      largely unknown. Here, we describe a new animal model for induction of aortic
      aneurysm in mice in which administration of deoxycorticosterone acetate (DOCA)
      and high salt or aldosterone and high salt, but not DOCA or high salt alone, to
      C57BL/6 male mice can potently induce aortic aneurysm formation and rupture in an
      age-dependent manner. This new aortic aneurysm mouse model is different from Ang
      II infusion mouse model and exhibits several unique features that mimic human
      aortic aneurysm.

PMID- 28500603
TI  - Fluorescence-Based Binding Assay for Screening Ligands of Angiotensin Receptors.
AB  - Binding assay is a common technique used to characterize ability of a ligand to
      interact with a specific biological target. A number of parameters, such as
      binding affinity, receptor density, and association/dissociation rate constants,
      can be measured by means of this technique. In most cases, implementation of the
      binding assay requires specific infrastructure for labeling and detecting the
      ligand, which impedes realization of this technique in a standard laboratory.
      Here we describe a simple fluorescence-based binding assay for angiotensin
      peptides and receptors, which does not require complex equipment and can be used
      for initial screening of the novel ligands or mutational studies.

PMID- 28500606
TI  - ?

PMID- 28500604
TI  - A Primer to Angiotensin Peptide Isolation, Stability, and Analysis by Nano-Liquid
      Chromatography with Mass Detection.
AB  - The renin-angiotensin system (RAS) is an important element of cardiovascular and
      renal physiology and targeting the RAS by renin inhibitors, angiotensin (Ang)
      converting enzyme (ACE) inhibitors and Ang II type 1 receptor antagonists is
      effective in the treatment of hypertension, heart failure, and atherosclerosis.
      Quantification of Ang peptides is critical to establish the status of the RAS,
      but it is challenging due to low Ang peptides concentrations (fmol/mL or fmol/g),
      abundance of interfering substances, post sampling conversions, and difficulties
      with the specificity of the assay.In this chapter, we describe a new nano-LC/MS
      based methodology for comprehensive, specific, sensitive, and accurate
      quantification of Ang peptides profile in plasma and tissue. We optimized sample
      pretreatment method (protein removal (acetonitrile precipitation) followed by
      solid-phase extraction (C18 silica bonded phase)), chromatographic conditions
      (reversed-phase nanochromatography with preconcentration), and mass detection
      (multiple reaction monitoring) of nine peptides: Ang-(1-12), Ang I (1-10), Ang-(1
      9), Ang II (1-8), [Ala1]-Ang II, Ang III (2-8), Ang IV (3-8), Ang-(1-7), and
      [Ala1]-Ang-(1-7). Assessment of plasma and cardiac concentrations of Ang peptides
      in genetically modified atherosclerotic apolipoprotein E/LDL receptor double
      knockout (ApoE-/-/LDLR-/-) mice vs. wild types revealed changes in renin
      angiotensin system consistent with an overactivation of ACE and impairment of
      ACE2. The method could be easily adopted for high-throughput analysis and for use
      in clinical applications such as diagnosis of the RAS abnormalities or monitoring
      of the RAS inhibition-based therapies.

PMID- 28500605
TI  - Analysis of Angiotensin Metabolism in the Kidney Using Mass Spectrometry.
AB  - The renin angiotensin system (RAS) is a highly complex enzymatic system
      consisting of multiple peptide hormones, enzymes, and receptors. A thorough
      characterization of angiotensin peptide metabolism is crucial for understanding
      pathological states associated with an imbalanced RAS. Here, we describe two
      matrix-assisted laser desorption/ionization (MALDI) mass spectrometric (MS)
      approaches for the assessment of in vitro and in situ RAS enzymatic activities in
      the kidney using the natural angiotensin peptide substrates. These MS techniques
      demonstrate high specificity and are superior over conventional
      spectrophotometric or colorimetric assays since multiple proteolytic cleavage
      sites can be detected, thus unraveling the complexity of the RAS.

PMID- 28500607
TI  - ?

PMID- 28500608
TI  - ?

PMID- 28500609
TI  - ?

PMID- 28500610
TI  - ?

PMID- 28500611
TI  - [Restorative proctocolectomy for ulcerative colitis : Long-term functional
      results and quality of life].
AB  - Restorative proctocolectomy with ileo-pouch-anal anastomosis is the standard
      procedure for ulcerative colitis. It provides complete removal of the diseased
      colorectum, avoids permanent ileostomy and allows the preservation of continence.
      Functional results and quality of life after restorative proctocolectomy are of
      great importance. Patients usually have 5-6 bowel movements per day, and
      continence is satisfactory in more than 90% of patients. A good pouch function
      strongly correlates with high quality of life. Postoperative septic complications
      are the main risk factor for bad pouch function and pouch failure; therefore
      nowadays most procedures are performed with a covering ileostomy. Quality of life
      is usually impaired by active ulcerative colitis, and restorative proctocolectomy
      improves the quality of life up to the level of a healthy reference population.
      Taken together, restorative proctocolectomy provides excellent results concerning
      function and quality of life.

PMID- 28500612
TI  - Electric smog: telemetry interference between ICD and LVAD.
AB  - Electromagnetic interferences between implantable cardioverter/defibrillators
      (ICD) and left ventricular assist devices (LVAD) impacting telemetry have been
      described in previous generations of ICD as well as LVAD, but have been
      predominantly overcome in current ICD generations. After introduction of a new
      fully magnetically levitated centrifugal continuous-flow circulatory pump, we
      report a case of tenacious telemetry interference between the HeartMate 3 LVAD
      and an ICD after battery exchange to an Iforia 5. Initialization of the initial
      telemetry handshake was only possible using several specific maneuvers
      simultaneously. In order to exclude device-device interference, we suggest to
      place the ICD above the LVAD before implantation and to test for possible
      telemetry interferences.

PMID- 28500613
TI  - Functional Diets Modulate lncRNA-Coding RNAs and Gene Interactions in the
      Intestine of Rainbow Trout Oncorhynchus mykiss.
AB  - The advent of functional genomics has sparked the interest in inferring the
      function of non-coding regions from the transcriptome in non-model species.
      However, numerous biological processes remain understudied from this perspective,
      including intestinal immunity in farmed fish. The aim of this study was to infer
      long non-coding RNA (lncRNAs) expression profiles in rainbow trout (Oncorhynchus
      mykiss) fed for 30 days with functional diets based on pre- and probiotics. For
      this, whole transcriptome sequencing was conducted through Illumina technology,
      and lncRNAs were mined to evaluate transcriptional activity in conjunction with
      known protein sequences. To detect differentially expressed transcripts, 880
      novels and 9067 previously described O. mykiss lncRNAs were used. Expression
      levels and genome co-localization correlations with coding genes were also
      analyzed. Significant differences in gene expression were primarily found in the
      probiotic diet, which had a twofold downregulation of lncRNAs compared to other
      treatments. Notable differences by diet were also evidenced between the coding
      genes of distinct metabolic processes. In contrast, genome co-localization of
      lncRNAs with coding genes was similar for all diets. This study contributes novel
      knowledge regarding lncRNAs in fish, suggesting key roles in salmons fed with in
      feed additives with the capacity to modulate the intestinal homeostasis and host
      health.

PMID- 28500615
TI  - Marijuana and the Risk of Fatal Car Crashes: What Can We Learn from FARS and NRS
      Data?
AB  - Lab studies have shown that marijuana can severely impair driving skills.
      Epidemiological studies, however, have been inconclusive regarding the
      contribution of marijuana use to crash risk. In the United States, case-control
      studies based on the merging of comparable crash Fatality Analysis Reporting
      System (FARS) and non-crash National Roadside Survey (NRS) data have been applied
      to assess the contribution of drugs to crash risk, but these studies have yielded
      confusing, even contradictory results. We hypothesize that such a divergence of
      results emanates from limitations in the databases used in these studies, in
      particular that of the FARS. The goal of this effort is to examine this
      hypothesis, and in doing so, illuminate the pros and cons of using these
      databases for drugged-driving research efforts. We took advantage of two
      relatively recent cannabis crash risk studies that, despite using similar
      databases (the FARS and the NRS) and following similar overall approaches,
      yielded opposite results (Li, Brady, & Chen, 2013; Romano, Torres-Saavedra, Voas,
      & Lacey, 2014). By identifying methodological similarities and differences
      between these efforts, we assessed how the limitations of the FARS and NRS
      databases contributed to contradictory and biased results. Because of its
      limitations, we suggest that the FARS database should neither be used to examine
      trends in drug use nor to obtain precise risk estimates. However, under certain
      conditions (e.g., based on data from jurisdictions that routinely test for drugs,
      with as little variation in testing procedures as possible), the FARS database
      could be used to assess the contribution of drugs to fatal crash risk relative to
      other sources of risk such as alcohol.

PMID- 28500614
TI  - IRF9-Stat2 Fusion Protein as an Innate Immune Inducer to Activate Mx and
      Interferon-Stimulated Gene Expression in Zebrafish Larvae.
AB  - Virus infection often causes large amounts of mortality during teleost larvae
      stage. Strong induction of innate immunity to increase survival rates of teleost
      larvae has been less reported. In this study, we present a zebrafish IRF9-Stat2
      fusion protein (zIRF9-S2C) as a strong innate immunity inducer and characterized
      induction of interferon-stimulated genes (ISGs) in zebrafish larvae. zIRF9-S2C
      could mimic IFN-stimulated gene factor 3 (ISGF3) complex to constitutively
      activate transcription of Mx promoter through IFN-stimulatory element (ISRE)
      sites. Mutation of two ISRE sites on Mx promoter reduced transactivation
      activities of Mx promoter induced by zIRF9-S2C. An electrophoretic mobility shift
      assay experiment shows that zIRF9-S2C could directly bind to two ISRE sites of Mx
      promoter. Induction of transactivation of Mx promoter by zIRF9-S2C shows
      significantly higher activity than by zebrafish IFN1 (zIFN1), IFNgamma
      (zIFNgamma), and Tetraodon IRF9-S2C (TnIRF9-S2C). zIRF9-S2C raises transcription
      of Mxa, Mxb, Mxc, Ifnphi1, Ifnphi2, and Ifnphi3 in zebrafish liver ((ZFL) cell
      line) cells and zebrafish larvae. Collectively, we suggest that IRF9-S2C could
      activate transcription of ISGs with species-specific recognition and could be an
      innate immunity inducer in teleost larvae.

PMID- 28500616
TI  - Significance of blood neutrophil-to-lymphocyte ratio for prognostic
      stratification of patients with gastroesophageal junction adenocarcinoma in the
      era of the 8th edition of the American Joint Committee on Cancer (AJCC8) staging.
AB  - The prognosis of patients with gastroesophageal junction (GOJ) adenocarcinoma
      depends mainly on the clinical staging, as described by the new AJCC8 (American
      Joint Committee on Cancer 8th edition). Evidence suggests that peripheral blood
      neutrophil-to-lymphocyte ratio (NLR) may be of prognostic significance in
      patients with upper gastrointestinal cancers. We examined the prognostic
      significance of NLR in the era of the new AJCC8 staging system. In this single
      centre cohort study, retrospective data on patients with operable GOJ
      adenocarcinoma treated with perioperative chemotherapy were analysed. The
      prognostic significance of baseline NLR in combination with AJCC8 clinical
      staging and other patient characteristics was examined for both time-to
      progression (TTP) and overall survival (OS). Of 316 patients, 245 (77.5%)
      underwent radical surgery. Fifty-one patients (16.2%) developed unresectable
      disease due to early disease progression. NLR was the only baseline factor
      independently associated with the development of early disease progression. AJCC8
      clinical staging was significantly associated with TTP and OS. In addition, NLR
      >= 3 was predictive of poorer TTP (p = 0.001) and OS (p = 0.002), confirmed in
      multivariate Cox-regression analysis. NLR >= 3 was prognostic, especially in
      patients with clinical stage III for TTP (p = 0.006) and OS (p = 0.025) and in
      patients with clinical stage IVA for OS (p = 0.017). NLR significantly improved
      the prognostic classification of patients by different AJCC8 clinical stages,
      with a c-index improved from 0.554 to 0.592 (p < 0.001). NLR was confirmed to be
      an independent prognostic factor in this cohort and could be used in combination
      with AJCC8 clinical staging to improve the baseline prognostic stratification of
      patients with newly diagnosed resectable GOJ adenocarcinoma.

PMID- 28500617
TI  - Post-chemotherapy PD-L1 expression correlates with clinical outcomes in Japanese
      bladder cancer patients treated with total cystectomy.
AB  - Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy
      that is frequently overexpressed in bladder cancer. In the present study, we
      examined whether PD-L1 expression is associated with clinical outcomes in bladder
      cancer patients. We enrolled 102 bladder cancer patients treated with cystectomy
      at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted
      an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD
      L1 expression was scored at three diagnostic levels (0/1/2). Of the 102 patients,
      82 were men (81.0%) and 20 were women (19.0%) (mean age 60 years, range 43-84
      years). Sixty-six patients (64.8%) had previously undergone neoadjuvant
      chemotherapy [neoadjuvant (+) group]. During the mean observation period of 54.5
      months, 42 patients had recurring disease (41.1%) and 34 died (33.3%). The 5-year
      cause-specific survival (CSS) rate was 66.6%; the 5-year disease-free survival
      (DFS) rate was 59.7%. In the neoadjuvant (+) group, the 5-year DFS rate was 65.0%
      for PD-L1 (-) patients and 31.7% for PD-L1 (+) patients (log-rank p = 0.006). In
      the neoadjuvant (+) groups, the 5-year CSS rate was 69.6% for PD-L1 (-) patients
      and 48.1% for PD-L1 (+) patients. Differences in CSS and DFS rates between PD-L1
      (-) and PD-L1 (+) patients in both treatment groups were statistically
      significant (log-rank p = 0.006 and 0.039, respectively.) Despite the small study
      size, our data suggest that post-chemotherapy PD-L1 expression is associated with
      poor prognosis in patients receiving neoadjuvant chemotherapy who had previously
      undergone cystectomy.

PMID- 28500619
TI  - Prevalence of cribra orbitalia in Pacopampa during the formative period in Peru.
AB  - Cribra orbitalia is characterized by an aggregation of small apertures in the
      orbital roof in response to marrow hypertrophy. This pathological change is
      indicative of biological stress during youth. We examined the prevalence of this
      lesion in Pacopampa, a ceremonial center of the formative period, located in the
      northern highlands of Peru. Using this evaluation of cribra orbitalia, we
      reconstructed aspects of the population's health and nutritional status during
      the formation of Andean civilization. We examined 41 orbits of 27 adult
      individuals (13 males, 14 females) and recorded the macroscopic presence or
      absence of cribra orbitalia. The presence or absence of cribra orbitalia was the
      same bilaterally for all 14 individuals having both orbits preserved. The
      pathology was present in two of the 13 males (15.4%), one of the 14 (7.1%)
      females, and three of 27 individuals (11.1%) for both sexes combined. There was
      no difference in the frequency between sexes. The prevalence of cribra orbitalia
      was found to be lower in Pacopampa than in the comparative data of coastal
      populations. It is reasonable to assume that the increase in social complexity in
      Pacopampa was probably unrelated to the decline in overall health of the people.

PMID- 28500618
TI  - Prognostic value of ABO blood types in young patients with breast cancer; a
      nationwide study in Korean Breast Cancer Society.
AB  - The purpose of this study was to investigate the relationship between ABO blood
      types and breast cancer survival in young Korean patients. This was a
      retrospective study of 115,474 patients who were surgically treated for primary
      breast cancer between 1987 and 2011 in Korea. All data were collected by the
      Korean Breast Cancer Society (KBCS) online breast cancer registry. Each hospital
      serologically examined the ABO blood types of patients before surgery. There was
      no significant difference in overall survival (OS) or breast cancer-specific
      survival (BCSS) among ABO blood types. Type of surgery; T stage; N stage;
      histologic grade; status of estrogen receptor, progesterone receptor, and HER2;
      and chemotherapy were significant prognostic factors of OS and BCSS in univariate
      analysis and multivariate analyses. Compared to women with blood type O, there
      was a difference in OS and BCSS for blood type A, blood type B, or blood type AB.
      Compared to blood group non-O, patients with blood group O were more likely to
      have favorable prognosis when younger than 40 years. Further follow-up studies
      are necessary to clarify the role of the impact of ABO blood types on prognosis
      of breast cancer.

PMID- 28500620
TI  - Relationship between disordered eating and self-identified sexual minority youth
      in a sample of public high school adolescents.
AB  - PURPOSE: To investigate the relationship between selected disordered eating
      behaviors and self-reported sexual minority status (gay/lesbian, bisexual, and
      unsure) among a representative sample of high school adolescents. METHODS: The
      2013 Centers for Disease Control and Prevention (CDC)-sponsored Connecticut Youth
      Risk Behavior Survey was utilized (N = 2242). Unadjusted and adjusted logistic
      regression analyses, separated by gender, examined sexual minority adolescents
      (gay/lesbian, bisexual, and unsure) and selected eating behaviors. Analyses
      adjusted for race, age, cigarette use, binge drinking, organized school activity
      participation, body mass index (BMI), and depression. RESULTS: Gay males were
      significantly more likely to report exercising or eating less to lose weight in
      the unadjusted models (p < 0.05) and fasting, vomiting, and taking diet pills in
      both adjusted (p < 0.05) and unadjusted models (p < 0.01) when compared to the
      referent heterosexual males. Bisexual females were significantly more likely to
      report fasting, vomiting, and taking diet pills in the unadjusted model (p <
      0.05) when compared to the referent heterosexual females and significantly less
      likely to report exercising or eating less to lose weight in the adjusted models
      (p < 0.05). CONCLUSIONS: Although additional studies are needed owing to small
      sample sizes, preliminary findings support previous research suggesting that high
      school-aged sexual minority youth subgroups are a priority target population for
      increased efforts to prevent disordered eating.

PMID- 28500621
TI  - Symptoms predicting psychosocial impairment in bulimia nervosa.
AB  - PURPOSE: The current study aimed to determine which particular eating disorder
      (ED) symptoms and related features, such as BMI and psychological distress,
      uniquely predict impairment in bulimia nervosa (BN). METHODS: Two hundred and
      twenty-two adults with BN completed questionnaires assessing ED symptoms, general
      psychological distress, and psychosocial impairment. Regression analyses were
      used to determine predictors which account for variance in impairment. RESULTS:
      Four variables emerged as significant predictors of psychosocial impairment:
      concerns with eating; concerns with weight and shape; dietary restraint; and
      general psychological distress. CONCLUSIONS: Findings support previous work
      highlighting the importance of weight and shape concerns in determining ED
      related impairment. Other ED symptoms, notably dietary restraint and concerns
      with eating, were also significant predictors as was psychological distress.
      Results suggest that cognitive aspects of EDs, in addition to psychological
      distress, may be more important determinants of impairment than behavioural
      symptoms, such as binge eating or purging.

PMID- 28500622
TI  - Implementation of a rapid assay of ADAMTS13 activity was associated with improved
      30-day survival rate in patients with acquired primary thrombotic
      thrombocytopenic purpura who received platelet transfusions.
AB  - BACKGROUND: Platelet (PLT) transfusions are probably harmful in patients with
      acquired idiopathic thrombotic thrombocytopenic purpura (aTTP). Introduction of a
      rapid assay for ADAMTS13 activity should reduce the time to definite diagnosis of
      aTTP, reduce the amount of inappropriately transfused PLT concentrates, and
      improve mortality and morbidity. STUDY DESIGN AND METHODS: We selected 265 aTTP
      patients with severe ADAMTS13 deficiency. Of these, 91 patients were diagnosed by
      March 2005 (Period 1), when ADAMTS13 activity was measured by von Willebrand
      factor multimer assay, which took 4 to 7 days until the result was reported. An
      additional 174 patients were diagnosed after April 2005 (Period 2), when the
      activity was measured by a chromogenic enzyme-linked immunosorbent assay, which
      took 1 to 2 days. RESULTS: We found no significant differences in 30-day survival
      rate between the two periods. Overall, 48 patients received PLT transfusions.
      Mortality was slightly greater between patients with (22.9%) versus without PLT
      transfusion (17.7%), but not significant. In Period 1, Cox proportional hazards
      regression analysis showed that older age (>=60 years) and PLT transfusion
      administration were independent factors associated with higher risks of 30-day
      mortality. In contrast, in Period 2, lower Rose-Eldor TTP severity score and use
      of plasma exchange and corticosteroid therapy were independent factors associated
      with higher survival rates while nonadministration of PLT transfusions was not.
      CONCLUSION: Our results indicate that PLT transfusions are harmful for aTTP
      patients when the definite diagnosis of severe ADAMTS13 deficiency is delayed. If
      it can be done as soon as possible, PLT transfusions for severe bleeding or
      surgical interventions might be allowed with subsequent plasmapheresis.

PMID- 28500623
TI  - Simultaneous inhibition of NMDA and mGlu1/5 receptors by levo-corydalmine in rat
      spinal cord attenuates bone cancer pain.
AB  - Bone cancer pain is a challenge for its not completely clarified mechanism and
      broad clinical morbidity. Therefore, novel and more effective drugs are urgent
      needed for improvement of patients' quality of life. Glutamate receptors have
      been associated with the development of the central sensitization of chronic
      pain. Inhibition of N-methyl-d-aspartate (NMDA) and metabotropic glutamate (mGlu)
      receptors can effectively attenuate bone cancer pain, respectively. Herein, our
      results indicated that levo-Corydalmine (l-CDL), a compound from Corydalis
      yanhusuo W.T. Wang, which has been used in traditional Chinese medicine for pain
      relief could effectively attenuate bone cancer pain induced by tibia bone cavity
      tumor cell implantation (TCI) through simultaneously inhibiting the NMDA and
      mGlu1/5 receptors in rat spinal cord without notable side effects. Both
      intragastric and intrathecal administration of l-CDL significantly alleviated the
      mechanical hypersensitivity induced by TCI in rats, and the analgesic effect of l
      CDL could be reversed by intrathecal administration of NMDA receptor agonist NMDA
      and mGlu1/5 receptor agonist DHPG but not AMPA receptor agonist AMPA. l-CDL could
      also selectively suppress NMDA and DHPG induced rapid rise in Ca2+ oscillations
      in primary cultures neurons of spinal cord in vitro. The antinociception of l-CDL
      were partially mediated by the reduced phosphorylation of PKC gamma and ERK1/2 in
      spinal cord of TCI rats in a NMDA and mGlu1/5 dependent manner. In conclusion,
      these results suggested that l-CDL attenuates TCI induced bone cancer pain
      through simultaneously inhibiting the NMDA and mGlu1/5 receptors and the
      downstream PKC gamma, ERK1/2 signaling pathways in the spinal cord.

PMID- 28500624
TI  - Temporal trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase
      antibody (ATPO) testing across two phases of iodine fortification in Tasmania
      (1995-2013).
AB  - CONTEXT: Tasmania is an island state of the Australian Commonwealth with a well
      documented history of mild iodine deficiency. Between 2001 and 2009, Tasmania
      experienced two incremental phases of iodine fortification. OBJECTIVE: To examine
      trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody
      (ATPO) testing and their relationship to different phases of iodine nutrition in
      the Tasmanian population between 1995 and 2013. DESIGN: Retrospective
      longitudinal study. SETTING AND PARTICIPANTS: The major primary care and largest
      public hospital pathology providers in Tasmania submitted data for all TSH and
      ATPO tests performed between 1995 and 2013. Data linkage methodology was used to
      determine trends in TSH and ATPO testing. RESULTS: A total of 1.66 million TSH
      assessments, involving 389,910 individual patients, were performed in Tasmania
      between 1995 and 2013. There was approximately a fourfold increase in the overall
      rate of TSH testing during this period with the rate of incident TSH assessment
      remaining relatively stable over the study period. The incidence of overt
      suppression and elevation of TSH (TSH<=0.1 mIU/L and >=10 mIU/L) declined 62.3%
      and 59.7%, respectively, with a trend for increased incidence of borderline TSH
      elevation >=4.0 mIU/L. The incidence of thyroid autoimmunity as determined by the
      proportion of abnormal ATPO results remained stable, with the absolute number of
      positive test results increasing during the study period. CONCLUSION: Iodine
      supplementation of this mildly iodine-deficient population was not associated
      with an obvious increase in incidence of overt thyroid dysfunction or
      autoimmunity. Whilst the volume of TSH testing increased over the study period,
      the increase was driven by patients undergoing follow-up TSH assessments.

PMID- 28500625
TI  - Adopting automated image analysis tool for fibrin network: Can we obtain clot
      properties for practical application?

PMID- 28500626
TI  - Using Eulerian video magnification to enhance detection of fasciculations in
      people with amyotrophic lateral sclerosis.
AB  - INTRODUCTION: This study seeks to determine whether the use of Eulerian video
      magnification (EVM) increases the detection of muscle fasciculations in people
      with amyotrophic lateral sclerosis (PALS) compared with direct clinical
      observation (DCO). METHODS: Thirty-second-long video recordings were taken of 9
      body regions of 7 PALS and 7 controls, and fasciculations were counted by DCO
      during the same 30-s period. The video recordings were then motion magnified and
      reviewed by 2 independent assessors. RESULTS: In PALS, median fasciculation count
      per body region was 1 by DCO (range 0-10) and 3 in the EVM recordings (range 0
      15; P < 0.0001). EVM revealed more fasciculations than DCO in 61% of recordings.
      In controls, median fasciculation count was 0 for both DCO and EVM. DISCUSSION:
      Compared with DCO, EVM significantly increased the detection of fasciculations in
      body regions of PALS. When it is used to supplement clinical examination, EVM has
      the potential to facilitate the diagnosis of ALS. Muscle Nerve 56: 1063-1067,
      2017.

PMID- 28500627
TI  - Widespread biphasic amyloidosis related to ipilimumab treatment for metastatic
      melanoma.

PMID- 28500628
TI  - Nonconvulsive electrotherapy in psychiatry: The treatment of the mental disorders
      of the Norwegian painter Edvard Munch.

PMID- 28500629
TI  - Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk
      of Neonatal Abstinence Syndrome.
AB  - OBJECTIVE: To develop a tool to predict the need for pharmacologic treatment of
      neonatal abstinence syndrome (NAS) within 36 hours from birth in infants at risk
      for opioid withdrawal. STUDY DESIGN: Retrospective study of infants born at
      gestation of >=34 weeks with in utero exposure to opioids during two time periods
      from January 2013 through October 2016. Period 1 was used to develop a predictive
      tool for validation during period 2. Birth weight, gestational age, four
      categories of opioid exposure, and individual scores for 21 withdrawal symptoms
      from the Modified Finnegan Score at 36 hours of life were recorded. During period
      1, a best subsets multiple regression analysis was performed on factors that were
      associated with pharmacotherapy on univariate analysis. Two tools were designed:
      one based on three highly predictive symptoms associated with need for
      pharmacotherapy for NAS and the other incorporating opioid exposure. Sensitivity,
      specificity, and positive and negative predictive values for the tools were
      calculated during period 2. RESULTS: The study included 264 infants (period 1,
      n=143; period 2, n=121). Polysubstance exposure and three withdrawal symptoms
      present at 36 hours of life that were significantly associated with
      pharmacotherapy for NAS comprised the tools. The "symptoms only tool" was able to
      predict that infants with a score <1 would not receive pharmacotherapy, and
      infants with scores of >=4 would receive pharmacotherapy with positive predictive
      values of 90% and 100%, respectively. When opioid exposure was included, the
      "symptoms + exposure tool" was able to predict that infants with a score of <=1
      would not receive pharmacotherapy and infants with scores of >=5 would receive
      pharmacotherapy with positive predictive values of 94% and 86%, respectively.
      CONCLUSION: An NAS prediction tool combining three clinical signs with and
      without category of opioid exposure had high positive predictive values for
      requiring and for not requiring pharmacotherapy. This tool may expedite
      pharmacotherapy decisions and optimize management for infants at risk for NAS.

PMID- 28500631
TI  - Exploring the value of mental health nurses working in primary care in England: A
      qualitative study.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Primary care and, in particular, general
      practice (GP) are often first point of access to health care. International
      evidence suggests that healthcare systems oriented towards primary care may
      produce better outcomes, at lower costs and with higher user satisfaction.
      Despite this, there are noted deficiencies and variations in the quality of care
      in primary care for patients with mental health problems. WHAT THIS PAPER ADDS TO
      EXISTING KNOWLEDGE?: Emerging models of providing mental health services in
      primary care are poorly understood. This paper evaluates a mental health nurse
      led Primary Care Liaison Service (PCLS), developed in 2011 in inner London. The
      findings suggest that this type of service can improve the quality of care for
      people presenting with mental health problems within primary care, specifically
      due to improved integration, clinical effectiveness, patient-centred care, access
      and efficiency. The study also highlighted challenges such as staff retention
      within this new role and setting appropriate referral criteria. WHAT ARE THE
      IMPLICATIONS FOR PRACTICE?: This is a relatively new service, and the cost
      effectiveness is not yet fully understood; however, commissioners may want to
      consider the potential benefits of a similar service in their area. The extent to
      which the findings are transferable will depend on service configuration and
      local demographics which can vary. Further research within this area could give
      more detail on the impact of such teams on health outcomes, recovery rates,
      secondary care referrals and accident and emergency attendances, and its cost
      effectiveness. ABSTRACT: Aims/Question General practice is typically the first
      point of access to healthcare. This study explores what value a Primary Care
      Liaison Nurse (PCLN) service, established in 2011, can bring to people with
      mental health problems in primary care. Method Semi-structured interviews were
      used to elicit participants' experiences and perspectives on the value of a PCLN
      service. Participants included ten interviews with seven general practitioners
      and three senior practitioners working in primary care mental health services.
      Thematic analysis, based on a 6-phase approach, was used to describe and explore
      the data collected. Results Five main themes were derived from the thematic
      analysis of the interviews relating to: integration; clinical effectiveness;
      patient centred care; access; and efficiency. Discussion The study suggests that
      the PCLN service can improve the quality of care and is generally highly valued
      by its stakeholders. The study identifies particularly valued elements of the
      service, including having a duty worker, as well as aspects which could be
      improved, such as patient criteria. Implications for practice This is a
      relatively new service and the cost-effectiveness is not yet fully understood;
      however, commissioners may want to consider the potential benefits of a similar
      service in their area.

PMID- 28500630
TI  - E2F is involved in radioresistance of carbon ion induced apoptosis via
      Bax/caspase 3 signal pathway in human hepatoma cell.
AB  - Deletion of p53, most common genetic alteration, is observed in human tumors and
      reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR)
      could induce p53-/- cancer cells apoptosis. However, little is known regarding
      the molecular mechanism in this type of cell apoptosis. The present studies have
      focused on mechanisms state of signaling pathways as an activator of the cell
      fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up
      regulation of E2F1 expression in cancer cells. This phenomenon was not observed
      in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in
      clonogenic survival, low level of cellular activity, G2 /M phase arrest,
      promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved
      caspase 3 proteins expressions without p53. Changes of E2F1 expressions could
      partly alter radioresistance in cancer cells. The results were suggested that
      heavy ion IR could induce p53-/- cancer cells apoptosis via E2F1 signal pathway.
      Our study provides a scientific rationale for the clinical use of heavy ion as
      radiotherapy in patients with p53-deficient tumors, which are often resistant to
      radiotherapy.

PMID- 28500632
TI  - Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766
      3p) and their potential targets in peripheral blood from vitiligo patients.
AB  - Vitiligo is an acquired skin disease with pigmentary disorder. Autoimmune
      destruction of melanocytes is thought to be major factor in the etiology of
      vitiligo. miRNA-based regulators of gene expression have been reported to play
      crucial roles in autoimmune disease. Therefore, we attempt to profile the miRNA
      expressions and predict their potential targets, assessing the biological
      functions of differentially expressed miRNA. Total RNA was extracted from
      peripheral blood of vitiligo (experimental group, n = 5) and non-vitiligo
      (control group, n = 5) age-matched patients. Samples were hybridized to a miRNA
      array. Box, scatter and principal component analysis plots were performed,
      followed by unsupervised hierarchical clustering analysis to classify the
      samples. Quantitative reverse transcription polymerase chain reaction (RT-PCR)
      was conducted for validation of microarray data. Three different databases,
      TargetScan, PITA and microRNA.org, were used to predict the potential target
      genes. Gene ontology (GO) annotation and pathway analysis were performed to
      assess the potential functions of predicted genes of identified miRNA. A total of
      100 (29 upregulated and 71 downregulated) miRNA were filtered by volcano plot
      analysis. Four miRNA were validated by quantitative RT-PCR as significantly
      downregulated in the vitiligo group. The functions of predicted target genes
      associated with differentially expressed miRNA were assessed by GO analysis,
      showing that the GO term with most significantly enriched target genes was axon
      guidance, and that the axon guidance pathway was most significantly correlated
      with these miRNA. In conclusion, we identified four downregulated miRNA in
      vitiligo and assessed the potential functions of target genes related to these
      differentially expressed miRNA.

PMID- 28500633
TI  - The novel role of pyrvinium in cancer therapy.
AB  - Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially
      approved by FDA for its anthelmintic properties and therapeutic function against
      animal-like protists such as Cryptosporidium parvum and Plasmodium falciparum in
      the 1950s. In the last 10 years, several studies have shown the novel activity of
      pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium
      could delay or inhibit tumor cell proliferation in cancer models including colon,
      breast, lung and prostate cancer, and some hematological malignancies. In this
      review, we discuss multiple critical signaling pathways and mechanisms underlying
      the anticancer effects of PP. In details, pyrvinium acts through the following
      main mechanisms: (i) energy and autophagy depletion; and (ii) inhibition of Akt
      and Wnt-beta-catenin-dependent pathways. Interestingly, pyrvinium has also shown
      potent anti-cancer stem cell activity. The overwhelming insights into the
      mechanism of anticancer properties of PP can help establishing novel and future
      anti-tumor treatment strategies.

PMID- 28500634
TI  - Inhibition of mast cell infiltration in an LL-37-induced rosacea mouse model
      using topical brimonidine tartrate 0.33% gel.
AB  - Brimonidine is a highly selective alpha2-adrenergic receptor agonist approved by
      the FDA for the treatment of rosacea. Rosacea is a major clinical disease with
      vasodilatation and rash on the centre of the face, and that brimonidine as a
      vasoconstrictor can act as a remedy for rosacea. However, there is no study of
      how brimonidine has an effect on rosacea-related immune cells or mechanisms in
      the skin to improve rosacea. In this study, we observed that clinical features of
      rosacea induced by LL-37 in Balb/c mice were improved after the application of
      brimonidine gel, and we also showed a marked decrease in the number of
      inflammatory cells, especially mast cells (MCs) histologically. Furthermore, we
      confirmed that mRNA levels of MC enzymes increased by LL-37 were reduced by
      brimonidine gel. To our knowledge, we first found that brimonidine has a
      mechanism of treating rosacea by reducing the number and mRNA levels of MC
      specific enzymes, an important immune cell in the pathogenesis of rosacea.

PMID- 28500636
TI  - Immune correlates of hepatitis B surface antigen spontaneous seroconversion in
      hepatitis B e antigen negative chronic hepatitis B patients.
AB  - BACKGROUND: Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg -ve
      chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen
      processing and impaired humoral response. We investigated the role of dendritic
      cells (DCs), T follicular helper (TFH) cells and plasma B cells in
      seroconversion. METHODS: HBeAg -ve (n=135) CHB patients with raised ALT at
      baseline were followed up. Patients undergoing HBsAg seroconversion (Gr. I, n=11)
      were compared with non-converters with low (Gr. II, n=17, HBV DNA<2000 IU/mL) or
      high HBV DNA (Gr. III, HBV DNA >2000 IU/mL, n=17). We measured cell phenotypes
      (TFH, B and DCs), HBV specific T-cell functionality [using pooled overlapping
      surface and core peptides], IL21 levels and gene expression analysis by qRT-PCR.
      RESULTS: Patients in Gr. I compared to Gr. II and III, had higher IL-21 levels
      (865 vs 276 vs 111 pg/mL, P=<.0001), TFH (CD4+ CXCR5+ ) cells (12.3 vs 4.67 vs
      2.77, P=<.001), inducible T-cell co-stimulator (ICOS) expression on TFH cells
      (20.0 vs 13.0 vs 13.68, P=.01), HBsAg specific IL-17 (9.40 vs 2.33 vs 2.61,
      P=<.001) and TNF-alpha secreting TFH17 cells (82 vs 1.43 vs 2.33, P=<.001),
      plasma B (CD19+ CD38+ ) cells (15.0 vs 5.08 vs 5.57, P=<.001), myeloid (17.80 vs
      5.39 vs 2.70, P=<.001) and plasmocytoid DCs (2.6 vs 0.43 vs 0.21, P=<.001).
      Plasma B-cell frequency (R2 =.64, P=.01) and IL-21 levels (R2 =.52, P=.003)
      correlated with anti-HBs titres in patients with HBsAg seroconversion.
      CONCLUSIONS: Dendritic cell and TFH cell mediated responses regulate humoral
      responses against HBV and play a major role in HBsAg seroconversion in CHB
      patients.

PMID- 28500637
TI  - Randomized controlled trials in status epilepticus: Size matters.

PMID- 28500635
TI  - Principles of pharmacological research of nutraceuticals.
AB  - LINKED ARTICLES: This article is part of a themed section on Principles of
      Pharmacological Research of Nutraceuticals. To view the other articles in this
      section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

PMID- 28500638
TI  - Adult intestinal colonization botulism mimicking brain death.

PMID- 28500640
TI  - Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the
      trichoydsplasia spinulosa polyomavirus.
AB  - BACKGROUND: Trichodysplasia spinulosa (TS) is a disfiguring folliculocentric
      cutaneous disease caused by infection with the trichodysplasia spinulosa
      polyomavirus (TSPyV). The TSPyV genome contains splice variants encoding the
      middle tumour (mT) antigen, although the potential role for TSPyV mT antigen in
      disease development remains unknown. OBJECTIVE: The current study was designed to
      investigate the mechanistic properties of TSPyV mT antigen, which may further our
      understanding of TS pathogenesis and provide insight into potential therapies.
      METHODS: A lentiviral packaging system was used to create an inducible cell line
      expressing TSPyV mT antigen. Proteins were extracted, separated by SDS-PAGE and
      subjected to Western blot analysis. Co-immunoprecipitation experiments and
      mutational analyses were also performed to evaluate protein-protein interactions
      of mT antigen. RESULTS: We describe a novel mechanism of action for mT antigen
      that involves hyperactivation of MEK, ERK and MNK1. Our findings suggest that
      dysregulation of these key signalling molecules depends upon TSPyV mT antigen
      interaction with protein phosphatase 2A (PP2A) via intact Zn binding motifs.
      CONCLUSION: Given that PP2A interaction and MEK/ERK/MNK1 phosphorylation are
      associated with high levels of cell proliferation and inflammation, our findings
      provide new evidence that TSPyV mT antigen may contribute to the pro
      proliferative conditions that lead to TS development.

PMID- 28500639
TI  - Comparison of transfusion thresholds during neonatal extracorporeal membrane
      oxygenation.
AB  - BACKGROUND: The objective of this study was to assess complications and patient
      outcomes associated with a lower reflexive red blood cell (RBC) transfusion
      threshold for neonates undergoing extracorporeal membrane oxygenation (ECMO) for
      hypoxic respiratory failure. STUDY DESIGN AND METHODS: A retrospective cohort
      study was conducted at a single tertiary neonatal intensive care unit of neonates
      undergoing ECMO support for refractory hypoxic respiratory failure for more than
      24 hours between December 2009 and December 2014. Seventy-two neonates received
      ECMO support for hypoxic respiratory failure for longer than 24 hours during the
      study period. Patient cohorts were determined based on transfusion threshold of
      hematocrit (Hct) level of less than 40% (December 2009-October 2012) and Hct
      level of less than 35% (November 2012-December 2014). RESULTS: Patients who had a
      lower threshold for transfusion (Hct < 35) had a lower mean Hct (38.3% vs. 41.4%,
      p < 0.0001) and received less total RBC transfusion volume (10.4 mL/kg/day vs.
      13.3 mL/kg/day, p = 0.002) while undergoing ECMO support. Survival off ECMO,
      survival to discharge, and complication rates were similar between the cohorts.
      CONCLUSIONS: A lower Hct threshold of 35% is associated with a reduction in RBC
      transfusion volume and does not appear to alter complication rates or patient
      outcomes for neonates receiving ECMO support for respiratory failure.

PMID- 28500642
TI  - Toward meaningful outcomes in teaching conversation and greeting skills with
      individuals with autism spectrum disorder.
AB  - We identified greeting and conversation deficits based on a parent interview and
      semistructured direct assessment for one child and two adolescents with autism
      spectrum disorder. We taught the greeting and conversation skills using
      behavioral skills training and within-session corrective feedback. A multiple
      baseline across conversation and greeting skills demonstrated experimental
      control over the effects of the teaching on acquisition and generalization to
      novel adults. We also conducted embedded reversals to assess maintenance of the
      acquired skills. Teaching produced robust acquisition, generalization,
      maintenance, and treatment extension for 15 of the 16 targeted skills across
      participants. Participant and parent reports indicated high levels of social
      validity for the intervention and outcomes. The results support individualized
      assessment and intervention for improving greeting and conversation skills during
      unscripted interactions, which are requisite for more extended and complex social
      interactions.

PMID- 28500641
TI  - T and B cell clonal expansion in Ras-associated lymphoproliferative disease
      (RALD) as revealed by next-generation sequencing.
AB  - Ras-associated lymphoproliferative disease (RALD) is an autoimmune
      lymphoproliferative syndrome (ALPS)-like disease caused by mutations in Kirsten
      rat sarcoma viral oncogene homologue (KRAS) or neuroblastoma RAS viral (V-Ras)
      oncogene homologue (NRAS). The immunological phenotype and pathogenesis of RALD
      have yet to be studied extensively. Here we report a thorough immunological
      investigation of a RALD patient with a somatic KRAS mutation. Patient lymphocytes
      were analysed for phenotype, immunoglobulin levels and T cell proliferation
      capacity. T and B cell receptor excision circles (TREC and KREC, respectively),
      markers of naive T and B cell production, were measured serially for 3 years. T
      and B cell receptor repertoires were studied using both traditional assays as
      well as next-generation sequencing (NGS). TREC and KREC declined dramatically
      with time, as did T cell receptor diversity. NGS analysis demonstrated T and B
      clonal expansions and marked restriction of T and B cell receptor repertoires
      compared to healthy controls. Our results demonstrate, at least for our reported
      RALD patient, how peripheral T and B clonal expansions reciprocally limit
      lymphocyte production and restrict the lymphocyte receptor repertoire in this
      disease. Decreased naive lymphocyte production correlated with a clinical
      deterioration in our patient's immune status, suggesting that TREC and KREC may
      be used as an aid in monitoring disease progression. Both the methodologies used
      here and the conclusions regarding immune homeostasis may be applicable to the
      research of ALPS and other immune dysregulation syndromes.

PMID- 28500643
TI  - Markers of the innate immune system in the cerebrospinal fluid in patients with
      severe depression.

PMID- 28500644
TI  - Stimulation of autophagy prevents intestinal mucosal inflammation and ameliorates
      murine colitis.
AB  - BACKGROUND AND PURPOSE: Defective autophagy contributes to the pathogenesis of
      inflammatory disorders such as inflammatory bowel disease and there are
      interactions between autophagy and inflammation. Here we have analysed the
      effects of autophagy stimulators on murine colitis. EXPERIMENTAL APPROACH: Mice
      were treated with intrarectal administration of 2,4,6-trinitrobenzenesulfonic
      acid (TNBS) (3.5 mg.20 g-1 ) and body weight was measured daily. Histological
      damage was scored 2 or 4 days after treatment. Some mice received trehalose (3%
      in drinking water 3 weeks before TNBS administration) or a daily administration
      of rapamycin (1.25 mg.kg-1 , i.p.), betanin (1 g.kg-1 , i.p.) or betanin + 3
      methyladenine (3MA) (10 mg.kg-1 , i.p.). Protein levels of p-mTOR, p62, LC3,
      BCL10, NFkappaB, IkappaBalpha and p-IkappaBalpha in mucosa were determined by
      Western blots and mRNA expression of TNFalpha, IL1beta, IL6, IL10, COX2, CCR7,
      CD11c, inducible NOS and CD86 by qRT-PCR. KEY RESULTS: Impaired autophagy
      associated with body weight loss and intestinal damage was detected in the mucosa
      of TNBS-treated mice. Administration of trehalose, rapamycin or betanin prevented
      the impaired autophagic flux induced by TNBS and decreased mucosal protein levels
      of BCL10, p-IkappaBalpha and NFkappaB-p65 and the expression of pro-inflammatory
      cytokines and M1 macrophage markers. Blockade of autophagosome formation by
      treatment with 3MA, prevented the reduction in protein levels of p62, BCL10, p
      IkappaBalpha and NFkappaB-p65 induced by betanin in TNBS-treated mice and
      weakened the protective effects of betanin on murine colitis. CONCLUSIONS AND
      IMPLICATIONS: Pharmacological stimulation of mucosal autophagy reduced intestinal
      inflammation and improved murine colitis.

PMID- 28500645
TI  - Development and validation of an LC-ESI-MS/MS approach to determine a highly
      hydrophobic drug, norcantharidin palmitate, and apply to a preliminary
      pharmacokinetic study in rats.
AB  - In order to investigate the pharmacokinetics of norcantharidin palmitate (NCTD
      PAL) in rats, we developed and validated an LC-ESI-MS/MS method. The NCTD-PAL and
      internal standard (triamcinoloneacetonide palmitate, TAP) were separated on a
      Phenomenex Kinetex(r)XB C18 column, and the mobile phase was composed of
      tetrahydrofuran (THF)-acetonitrile (20/80, v/v) and an aqueous phase containing
      0.2% ammonium hydroxide at a flow rate of 0.3 mL/min. The ESI interface operated
      in positive mode was used to acquire the mass spectrometric data, and the
      transition ions were m/z 635.50 -> 168.95 and 673.65 -> 397.13 for NCTD-PAL and
      IS, respectively. The method had a linear range of 10-2000 ng/mL with a
      correlation coefficient of >0.99. The accuracy (RE, %) was within +/-10.1%, and
      the intra- and inter-day precisions (RSD, %) were 10.9 and 13.8%, respectively.
      The extraction recovery of NCTD-PAL at different concentrations ranged from 89.3
      to 102.0%. The validated approach was efficaciously applied to a pharmacokinetic
      study of NCTD-PAL in rats via intravenous injection. Based on these results
      obtained, this method is practical and suitable for a wide range of applications.

PMID- 28500646
TI  - High-throughput metabolic profiling based on small amount of hepatic cells.
AB  - Common metabolomics platforms require about 106 cells, which has a limited
      throughput due to the time-consuming steps of cell culture and preparation. There
      is a demand for metabolic profiling methods to improve analytical throughput and
      detection sensitivity based on small amount of cells. In this study, we proposed
      a high-throughput scheme, integrating 96-well plate cell cultivation, in-situ
      cell pretreatment, and sensitive dansylation labeling coupled with LC-MS analysis
      of metabolites inside HepG2 cells (of the order of magnitude of 103 cells in each
      well). A simple and rapid cell pretreatment was performed showing good extraction
      efficiency and good precision (the RSDs smaller than 5%) for polar metabolites.
      The recovery in metabolite extraction evaluated with three isotope-labeled amino
      acids was from 89.7 to 106.3% at low, medium, and high concentrations. The
      suitability of the method was illustrated by exploring influences of different
      fatty acids on HepG2 cells.

PMID- 28500647
TI  - Serum brain-derived neurotrophic factor and interleukin-6 response to high-volume
      mechanically demanding exercise.
AB  - INTRODUCTION: The aim of this study was to follow circulating brain-derived
      neurotrophic factor (BDNF) and interleukin-6 (IL-6) levels in response to severe
      muscle-damaging exercise. METHODS: Young healthy men (N = 10) performed a bout of
      mechanically demanding stretch-shortening cycle exercise consisting of 200 drop
      jumps. Voluntary and electrically induced knee extension torque, serum BDNF
      levels, and IL-6 levels were measured before and for up to 7 days after exercise.
      RESULTS: Muscle force decreased by up to 40% and did not recover by 24 hours
      after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise,
      whereas IL-6 increased immediately and 1 hour after but recovered to baseline by
      24 hours after exercise. IL-6 and 100-Hz stimulation torque were correlated (r = 
      0.64, P < 0.05) 24 hours after exercise. DISCUSSION: In response to acute, severe
      muscle-damaging exercise, serum BDNF levels decrease, whereas IL-6 levels
      increase and are associated with peripheral fatigue. Muscle Nerve 57: E46-E51,
      2018.

PMID- 28500649
TI  - A comparative study using thrombin generation and three different INR methods in
      patients on Vitamin K antagonist treatment.
AB  - INTRODUCTION: Vitamin K antagonist (VKA) treatment requires routine monitoring
      using the international normalized ratio (INR). However, different INR assays may
      vary in their results. The aim of this study was to assess the agreement of three
      different INR methods, compared with thrombin generation, in patients on VKA
      treatment. METHODS: Sixty patients attending the Anticoagulation Clinic at Mater
      Dei Hospital (Msida, Malta) for VKA monitoring between August and September 2015
      were enrolled. The INR was tested using a point-of-care (POC) device (CoaguChek
      XS Plus, Roche Diagnostics) for both capillary and venous blood samples, a photo
      optical (Sysmex CS-2100i/CA-1500, Siemens) and a mechanical clot detection system
      (Thrombolyzer XRC, Behnk Elektronik). All assays used human recombinant
      thromboplastin as reagent. Thrombin generation was performed using the calibrated
      automated thrombogram. RESULTS: There was a negative curvilinear correlation
      between the endogenous thrombin potential and different INR assays (r<=-.75) and
      a strong positive linear correlation between the CoaguChek XS Plus on capillary
      samples and the other INR methodologies (r>=.96). CONCLUSION: All different INR
      assays showed good correlation with the thrombin generation potential. The POC
      INR showed one of the highest correlation coefficients with thrombin generation,
      confirming the POC devices as an accurate, valid alternative to laboratory INR in
      VKA patients.

PMID- 28500650
TI  - Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to
      epigenetic modifications in mice lacking the post-synaptic scaffolding protein
      SHANK1: Implications for autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders
      characterized by persistent deficits in social communication/interaction,
      together with restricted/repetitive patterns of behavior. ASD is among the most
      heritable neuropsychiatric conditions, and while available evidence points to a
      complex set of genetic factors, the SHANK gene family has emerged as one of the
      most promising candidates. Here, we assessed ASD-related phenotypes with
      particular emphasis on social behavior and cognition in Shank1 mouse mutants in
      comparison to heterozygous and wildtype littermate controls across development in
      both sexes. While social approach behavior was evident in all experimental
      conditions and social recognition was only mildly affected by genotype, Shank1-/-
      null mutant mice were severely impaired in object recognition memory. This effect
      was particularly prominent in juveniles, not due to impairments in object
      discrimination, and replicated in independent mouse cohorts. At the
      neurobiological level, object recognition deficits were paralleled by increased
      brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of
      Shank1-/- mice; yet BDNF levels did not differ under baseline conditions. We
      therefore investigated changes in the epigenetic regulation of hippocampal BDNF
      expression and detected an enrichment of histone H3 acetylation at the Bdnf
      promoter1 in Shank1-/- mice, consistent with increased learning-associated BDNF.
      Together, our findings indicate that Shank1 deletions lead to an aberrant
      cognitive phenotype characterized by severe impairments in object recognition
      memory and increased hippocampal BDNF levels, possibly due to epigenetic
      modifications. This result supports the link between ASD and intellectual
      disability, and suggests epigenetic regulation as a potential therapeutic target.

PMID- 28500651
TI  - Predictors of Response in Emergency Department Patients Receiving Intravenous
      Opioids for Severe Pain.
AB  - The primary objective of this study was to identify significant environmental and
      patient characteristics of emergency department (ED) patients who responded to
      intravenous (IV) hydromorphone and IV morphine for severe pain. Secondary
      objectives were to investigate the individual effect of the significant
      environmental and patient characteristics of responders, and to assess the nature
      and strength of the correlation of initial dose and change in pain score from
      arrival to pre-administration. A retrospective chart review was performed in
      patients who received IV hydromorphone or morphine in the ED for severe pain. Key
      evaluated patient characteristics included patient demographics, recent opioid
      use, history of drug or alcohol abuse, and pain location, among others. Key
      evaluated environmental characteristics included initial opioid administered,
      time to first dose, initial pain score, and initial dose of opioid administered,
      among others. Environmental and patient characteristics associated with response
      to pain management were first identified using bivariate analyses and then
      entered into a multiple stepwise logistic regression mode. Patients were excluded
      if they were younger than 18 years, did not have a follow-up pain score within 2
      hours of drug administration, or if they were discharged from the ED within 1
      hour of administration. Patients meeting the inclusion criteria were grouped into
      two cohorts based on response and lack of response to treatment. A total of 200
      patients were included. A decrease in pain score from arrival until pre
      administration pain score and an inactive tobacco history had a positive
      association with response (odds ratio [OR] 1.488, 95% confidence interval [CI]
      1.088-2.036, p=0.013, and OR 1.835, 95% CI 0.801-4.200, overall p=0.022,
      respectively). A higher initial dose and an active tobacco history had a negative
      association with response (OR 0.715, 95% CI 0.580-0.881, p=0.002, and OR 0.582,
      95% CI 0.296-1.144, overall p=0.022, respectively). Two characteristics were
      associated with response to IV opioid pain management in the ED, inactive tobacco
      history and an increase in pain score from arrival until pre-administration, and
      two characteristics were associated with nonresponse to IV opioid pain management
      in the ED, active tobacco history and a higher initial dose. Previous literature
      supports both characteristics identified as risk factors but does not support
      either characteristic identified as protective factors, prompting the need for
      further research.

PMID- 28500652
TI  - Freeze-dried plasma enhances clot formation and inhibits fibrinolysis in the
      presence of tissue plasminogen activator similar to pooled liquid plasma.
AB  - BACKGROUND: Systemic hyperfibrinolysis is an integral part of trauma-induced
      coagulopathy associated with uncontrolled bleeding. Recent data suggest that
      plasma-first resuscitation attenuates hyperfibrinolysis; however, the
      availability, transport, storage, and administration of plasma in austere
      environments remain challenging and have limited its use. Freeze-dried plasma
      (FDP) is a potential alternative due to ease of storage, longer shelf life, and
      efficient reconstitution. FDP potentially enhances clot formation and resists
      breakdown better than normal saline (NS) and albumin and similar to liquid
      plasma. STUDY DESIGN AND METHODS: Healthy volunteers underwent citrated blood
      draw followed by 50% dilution with NS, albumin, pooled plasma (PP), or pooled
      freeze-dried plasma (pFDP). Citrated native and tissue plasminogen activator (t
      PA)-challenge (75 ng/mL) thrombelastography were done. Proteins in PP, pFDP, and
      albumin were analyzed by mass spectroscopy. RESULTS: pFDP and PP had superior
      clot-formation rates (angle) and clot strength (maximum amplitude) compared with
      NS and albumin in t-PA-challenge thrombelastographies (angle: pFDP, 67.9 degrees;
      PP, 67.8 degrees; NS, 40.6 degrees; albumin, 35.8 degrees; maximum amplitude:
      pFDP, 62.4 mm; PP, 63.5 mm; NS, 44.8 mm; albumin, 41.1 mm). NS and albumin
      dilution increased susceptibility to t-PA-induced hyperfibrinolysis compared with
      pFDP and PP (NS, 62.4%; albumin, 62.6%; PP, 8.5%; pFDP, 6.7%). pFDP was similar
      to PP in the attenuation of t-PA-induced fibrinolysis. Most proteins (97%) were
      conserved during the freeze-dry process, with higher levels in 12% of pFDP
      proteins compared with PP. CONCLUSION: pFDP enhances clot formation and
      attenuates hyperfibrinolysis better than NS and albumin and is a potential
      alternative to plasma resuscitation in the treatment of hemorrhagic shock.

PMID- 28500653
TI  - Blood transfusion in the surgical treatment of adolescent idiopathic scoliosis-a
      single-center experience of patient blood management in 210 cases.
AB  - BACKGROUND: The surgical treatment of adolescent idiopathic scoliosis can be
      associated with substantial blood loss, requiring allogeneic red blood cell (RBC)
      transfusion. This study describes the use of RBC and the effect of a standardized
      perioperative patient blood management program. STUDY DESIGN AND METHODS:
      Patients treated with posterior instrumented fusion were consecutively enrolled
      over a 6-year period. Patient blood management strategies were implemented in
      2011, including prophylactic tranexamic acid, intraoperative permissive
      hypotension, restrictive fluid therapy (including avoidance of synthetic
      colloids), restrictive RBC trigger according to institutional standardized
      protocol, the use of cell savage, and goal-directed therapy according to
      thrombelastography. RESULTS: In total, 210 patients were included. 64 patients
      (31%) received RBC transfusions. A decline in the intraoperative rate of RBC
      transfusion was observed, from 77% in 2011 to 13% in 2016 (p < 0.001). Patients
      in the transfusion group had a significantly larger major curve, lower
      preoperative hemoglobin, higher estimated blood loss, and an increased use of
      crystalloid volume resuscitation. Multiple logistic regression showed that
      significant predictors for RBC transfusion were preoperative hemoglobin level
      (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.27-0.57), estimated blood
      loss (OR, 1.26; 95% CI, 1.15-1.42), and year of surgery (indicating the effect of
      patient blood management) (OR per year, 0.76; 95% CI, 0.58-0.99). CONCLUSION: A
      perioperative patient blood management program substantially reduced the need for
      RBC transfusion. A preoperative evaluation of anemia is essential to further
      minimize transfusion rates.

PMID- 28500654
TI  - Altered timing of riboflavin and ultraviolet light pathogen inactivation improves
      platelet in vitro quality.
AB  - BACKGROUND: The platelet (PLT) storage lesion is in part caused by the collection
      and/or production process. Pathogen inactivation (PI) further accelerates its
      development leading to a reduced in vitro PLT functionality and hence quality.
      Although the treatment of PLT concentrates (PCs) with riboflavin and ultraviolet
      light PI should occur within 22 hours of collection, in this study the impact of
      treatment timing on in vitro PLT quality was investigated. STUDY DESIGN AND
      METHODS: Apheresis PCs were PI treated on the day of production or on Days 1, 3,
      or 4 of storage or left untreated as control. A panel of in vitro variables was
      used to monitor quality throughout 7-day storage, including metabolism, PLT
      activation, and release of microparticles. Changes in phosphorylation profiles of
      proteins in the lysate and levels of PLT factor 4, thrombospondin, and epidermal
      growth factor (EGF) in the releasate were analyzed by immunoblots or enzyme
      linked immunosorbent assay. RESULTS: By Day 7 of storage, units illuminated on
      Day 4 showed a smaller impact of the PI process than units treated on the day of
      production or one day after on PLT quality such as PLT activation; metabolic
      activity; microvesicle and EGF release; and phosphorylation of p38, ERK, and
      HSP27. PCs treated on Day 3 of storage displayed an intermediate effect.
      CONCLUSION: The timing of PI treatment of PCs influences in vitro PLT quality.
      Based on these results, timing recommendations should be reconsidered. If PI is
      applied, inventory management in blood banks might improve with a more flexible
      collection and treatment regime.

PMID- 28500655
TI  - Discovery and validation of candidate host DNA methylation markers for detection
      of cervical precancer and cancer.
AB  - Human papillomavirus (HPV) testing has been recently introduced as an alternative
      to cytology for cervical cancer screening. However, since most HPV infections
      clear without causing clinically relevant lesions, additional triage tests are
      required to identify women who are at high risk of developing cancer. We
      performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue
      specimens from women with benign HPV16 infection and histologically confirmed
      cervical intraepithelial neoplasia grade 3, and cancer using a bead-based
      microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in
      individual CpG sites were compared using a t-test, and results were summarized by
      computing p-values. A total of 12 candidate genes (ADCYAP1, ASCL1, ATP10, CADM1,
      DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17 and TMEFF2) identified by DNA
      methylation profiling, plus an additional three genes identified from the
      literature (EPB41L3, MAL and miR-124) were chosen for validation in an
      independent set of 167 liquid-based cytology specimens using pyrosequencing and
      targeted, next-generation bisulfite sequencing. Of the 15 candidate gene markers,
      10 had an area under the curve (AUC) of >= 0.75 for discrimination of high grade
      squamous intraepithelial lesions or worse (HSIL+) from <HSIL cytology using at
      least one assay. Overall, SOX1, DCC, and EPB41L3 showed the best discrimination
      with AUC values of >=0.80, irrespective of methylation detection assay. In
      addition to verifying candidate markers from the literature (e.g., SOX1 and
      EPB41L3), we identified novel markers that may be considered for detection of
      cervical precancer and cancer and warrant further validation in prospective
      studies.

PMID- 28500656
TI  - A Stable N-Annulated Perylene-Bridged Bisphenoxyl Diradicaloid and the
      Corresponding Boron Trifluoride Complex.
AB  - Organic pi-extended radicals display unique electronic structures, and could be
      used as promising functional materials. However, design and synthesis of stable
      radicals are challenging for chemists due to their high reactivity. In this work,
      we synthesized a stable N-annulated perylene-bridged bisphenoxyl diradicaloid,
      and its complex with Lewis acid boron trifluoride. Their ground-state geometric
      and electronic structures were systematically studied by various experimental
      methods, including X-ray crystallographic analysis, variable-temperature NMR
      spectroscopy, electron-spin resonance spectroscopy (ESR), and superconducting
      quantum interference device (SQUID) measurements, supported by density functional
      theory. Both were observed as open-shell singlet diradicaloids in the ground
      state. The bisphenoxyl diradicaloid demonstrated string features of strong near
      infrared (NIR) absorption, closely packed pi-dimer structure in crystals,
      amphoteric redox behavior with a small HOMO-LUMO energy band gap, and a rather
      small singlet-triplet gap, whereas the complex showed very different
      photophysical, electrochemical, and magnetic properties. Our studies provide an
      efficient method of making stable diradicaloids by Lewis acid/base complexation.

PMID- 28500658
TI  - Evaluation of photoaging scales in an elderly male population.

PMID- 28500657
TI  - Modulation of Kv 11.1 (hERG) channels by 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4
      (trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), a novel small molecule
      activator.
AB  - BACKGROUND AND PURPOSE: Activators of Kv 11.1 (hERG) channels have potential
      utility in the treatment of acquired and congenital long QT (LQT) syndrome. Here,
      we describe a new hERG channel activator, 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4
      (trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), with a chemical structure
      distinct from previously reported compounds. EXPERIMENTAL APPROACH: Conventional
      electrophysiological methods were used to assess the effects of ITP-2 on hERG1a
      and hERG1a/1b channels expressed heterologously in HEK-293 cells. KEY RESULTS:
      ITP-2 selectively increased test pulse currents (EC50 1.0 MUM) and decreased tail
      currents. ITP-2 activated hERG1a homomeric channels primarily by causing large
      depolarizing shifts in the midpoint of voltage-dependent inactivation and
      hyperpolarizing shifts in the voltage-dependence of activation. In addition, ITP
      2 slowed rates of inactivation and made recovery from inactivation faster.
      hERG1a/1b heteromeric channels showed reduced sensitivity to ITP-2 and their
      inactivation properties were differentially modulated. Effects on midpoint of
      voltage-dependent inactivation and rates of inactivation were less pronounced for
      hERG1a/1b channels. Effects on voltage-dependent activation and activation
      kinetics were not different from hERG1a channels. Interestingly, hERG1b channels
      were inhibited by ITP-2. Inactivation-impairing mutations abolished activation by
      ITP-2 and led to inhibition of hERG channels. ITP-2 exerted agonistic effect from
      extracellular side of the membrane and could activate one of the arrhythmia
      associated trafficking-deficient LQT2 mutants. CONCLUSIONS AND IMPLICATIONS: ITP
      2 may serve as another novel lead molecule for designing robust activators of
      hERG channels. hERG1a/1b gating kinetics were differentially modulated by ITP-2
      leading to altered sensitivity. ITP-2 is capable of activating an LQT2 mutant and
      may be potentially useful in the development of LQT2 therapeutics.

PMID- 28500659
TI  - Insulin sensitivity in relation to fat distribution and plasma adipocytokines
      among abusers of anabolic androgenic steroids.
AB  - OBJECTIVE: Abuse of anabolic androgenic steroids (AAS) is prevalent among young
      men, but information regarding effects on insulin sensitivity and fat
      distribution is limited. The objective was to investigate insulin sensitivity in
      relation to fat distribution and adipocytokines among current and former AAS
      abusers compared with controls. DESIGN: Cross-sectional study among men involved
      in recreational strength training. Current and former AAS abusers (n=37 and n=33)
      and controls (n=30) volunteered from the community. METHODS: We assessed insulin
      sensitivity by Matsuda index (oral glucose tolerance test). Using overnight
      fasting blood samples, adiponectin and leptin were measured. Body composition and
      fat distribution, including visceral adipose tissue (VAT), were assessed by dual
      energy X-ray absorptiometry. RESULTS: Current and former AAS abusers displayed
      lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45;
      -1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS
      abusers and subnormal among former AAS abusers compared with controls. Current
      AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm3 ,
      P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In
      contrast, former AAS abusers showed highest leptin concentrations and body fat %.
      Multivariate linear regressions identified VAT as independent predictor of lower
      Matsuda index among current AAS abusers compared with controls; while body fat %
      independently predicted lower Matsuda index among former AAS abusers.
      CONCLUSIONS: Both current and former AAS abusers displayed lower insulin
      sensitivity which could be mediated by higher VAT and total body fat %,
      respectively.

PMID- 28500661
TI  - Is mealworm or shrimp allergy indicative for food allergy to insects?
AB  - SCOPE: The growing world population is a key driver for the exploration of
      sustainable protein sources to ensure food security. Mealworm and other insects
      are promising candidates. Previously we found that shrimp allergic patients are
      at risk for mealworm allergy, and that mealworm can induce a primary allergy .
      This study set out to investigate the allergenic potential of edible insects,
      suggested for human consumption by agencies such as WHO/FAO, in both the shrimp
      (potentially cross-reactive) and primary mealworm allergic population. The
      following insects were studied: mealworm, house cricket, giant mealworm, lesser
      mealworm, African grasshopper, large wax moth, and black soldier fly. METHODS AND
      RESULTS: Fifteen shrimp (mealworm sensitized or allergic) patients and four
      primary mealworm allergic subjects, who participated in previous studies, were
      included. All shrimp allergic patients were sensitized to multiple insects with
      similar response profiles for all insects tested. Primary mealworm allergic
      patients, showed IgE binding to proteins from only a few insects on immunoblot,
      although basophil activation test was positive for all tested insects.
      CONCLUSION: Shrimp allergic patients are most likely at risk of food allergy to
      mealworm and other insects. Primary mealworm allergy does not mean subjects are
      likely to react to all insects.

PMID- 28500662
TI  - Application of a novel bioreactor for in vivo engineering of pancreas tissue.
AB  - Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells.
      Organ transplantation is an acceptable treatment for native organ failure.
      However, it is associated with several problems due to a number of reasons, such
      as the lack of appropriate donors and immunosuppression. In our present study, a
      novel model is presented for in vivo recellularization of acellular pancreas by
      implanting between the host pancreas and the adjacent omental flap. In this
      study, the pancreases were harvested and cannulated via the common bile duct and
      then, the scaffolds were acellularized by a detergent-based protocol. After that,
      the abdomens of 35 rats were opened and the spleen was extracted with the
      adjacent omentum, and placed outside the abdomen. The acellularized scaffold was
      stretched over the host pancreas and the omentum was wrapped around it to make a
      sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked
      with Prolene 4-0 on four sides. All samples were biopsied at 14, 30, 60, 90, and
      120 days post-transplantation. The result showed marked recellularization of
      acellularized pancreas with visible neovascularization and neobeta-cells with
      minimal inflammatory response. This study provides a new approach to produces a
      normal-like pancreas by allograft transplantation for pancreas tissue
      engineering. We observed that in vivo transplantation of acellularized pancreas
      can promote recellularization, proliferation, and differentiation by blood
      circulation. These findings support that in vivo studies can contribute to
      finding faster solutions for the treatment of diabetes.

PMID- 28500660
TI  - Association between wrist ratio and carpal tunnel syndrome: Effect modification
      by body mass index.
AB  - INTRODUCTION: Previous studies have reported higher wrist ratios (WR) related to
      carpal tunnel syndrome (CTS) but have not assessed effect modification by obesity
      and may have inadequately controlled for confounders. METHODS: Baseline data of a
      multicenter prospective cohort study were analyzed. CTS was defined by nerve
      conduction study (NCS) criteria and symptoms. RESULTS: Among the 1,206
      participants, a square-shaped wrist was associated with CTS after controlling for
      confounders (prevalence ratio = 2.27; 95% confidence interval [95% CI], 1.33
      3.86). Body mass index (BMI) was a strong effect modifier on the relationship
      between WR and both CTS and abnormal NCS results, with normal weight strata of
      rectangular versus square wrists = 8.18 (95% CI, 1.63-49.96) and 7.12 (95% CI,
      2.19-23.16), respectively. DISCUSSION: A square wrist is significantly associated
      with CTS after controlling for confounders. Effect modification by high BMI
      masked the eightfold magnitude adjusted relationship seen between WR and CTS
      among normal weight participants. Muscle Nerve 56: 1047-1053, 2017.

PMID- 28500663
TI  - Obesity and related risk of myeloproliferative neoplasms among israeli
      adolescents.
AB  - OBJECTIVE: Obesity has been associated with various malignancies, but a clear
      association between overweight and myeloproliferative neoplasms (MPN) has not
      been established. METHODS: This study assessed the association between adolescent
      obesity and future risk for MPN. Data on 2,516,256 Israeli adolescents, who
      underwent a compulsory general health examination at ages 16 to 19, between 1967
      and 2011, were linked to the National Cancer Registry in this nationwide,
      population-based cohort study. Cox proportional hazards models were used to
      estimate the hazard ratio (HR) for MPN associated with BMI measured at
      adolescence. RESULTS: The mean follow-up of 19.86 +/- 12.15 years reflected
      49,977,521 person years, during which 433 examinees developed MPN, primarily
      chronic myelogenous leukemia, polycythemia vera, and essential thrombocythemia.
      Obesity (BMI >= 95th percentile) in adolescence significantly predicted increased
      risk of MPN with HR (adjusted for sex) of 1.81 (95% confidence interval 1.13
      2.92, P = 0.014). CONCLUSIONS: Adolescent obesity might be related to an
      increased incidence of myeloproliferative neoplasms.

PMID- 28500664
TI  - Ligand-Promoted Rhodium(III)-Catalyzed ortho-C-H Amination with Free Amines.
AB  - Ligand development for rhodium(III)-catalyzed C-H activation reactions has
      largely been limited to cyclopentadienyl (Cp) based scaffolds. 2-Methylquinoline
      has now been identified as a feasible ligand that can coordinate to the metal
      center of Cp*RhCl to accelerate the cleavage of the C-H bond of N
      pentafluorophenylbenzamides, providing a new structural lead for ligand design.
      The compatibility of this reaction with secondary free amines and anilines also
      overcomes the limitations of palladium(II)-catalyzed C-H amination reactions.

PMID- 28500665
TI  - Load-induced changes in the diffusion tensor of ovine anulus fibrosus: A pilot
      MRI study.
AB  - PURPOSE: To assess the feasibility of diffusion tensor imaging (DTI) for
      evaluating changes in anulus fibrosus (AF) microstructure following uniaxial
      compression. MATERIALS AND METHODS: Six axially aligned samples of AF were
      obtained from a merino sheep disc; two each from the anterior, lateral, and
      posterior regions. The samples were mechanically loaded in axial compression
      during five cycles at a rate and maximum compressive strain that reflected
      physiological conditions. DTI was conducted at 7T for each sample before and
      after mechanical testing. RESULTS: The mechanical response of all samples in
      unconfined compression was nonlinear. A stiffer response during the first loading
      cycle, compared to the remaining cycles, was observed. Change in diffusion
      parameters appeared to be region-dependent. The mean fractional anisotropy
      increased following mechanical testing. This was smallest in the lateral (2% and
      9%) and largest in the anterior and posterior samples (17-25%). The mean average
      diffusivity remained relatively constant (<2%) after mechanical testing in the
      lateral and posterior samples, but increased (by 5%) in the anterior samples. The
      mean angle made by the principal eigenvector with the spine axis in the lateral
      samples was 73 degrees  and remained relatively constant (<2%) following
      mechanical testing. This angle was smaller in the anterior (55 degrees ) and
      posterior (47 degrees ) regions and increased by 6-16 degrees  following
      mechanical testing. CONCLUSION: These preliminary results suggest that axial
      compression reorients the collagen fibers, such that they become more
      consistently aligned parallel to the plane of the endplates. LEVEL OF EVIDENCE: 1
      Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1723-1735.

PMID- 28500666
TI  - Bioactivity and mineralization of natural hydroxyapatite from cuttlefish bone and
      Bioglass(r) co-sintered bioceramics.
AB  - In this study, bioactive hydroxyapatite (HAP)-based bioceramics starting from
      cuttlefish bone powders have been prepared and characterized. In particular,
      fragmented cuttlefish bone was co-sintered with 30 wt% of Bioglass(r) -45S5 to
      synthesize HAP-based powders with enhanced mechanical properties and bioactivity.
      Commercial synthetic HAP was treated following the same procedure and used as a
      reference. The structure and composition of the bioceramics formulations were
      characterized using Fourier transform infrared spectroscopy, X-ray diffraction
      and scanning electron microscopy. After the thermal treatment of cuttlefish bone
      powder added with 30 wt% Bioglass, new phases with compositions of sodium calcium
      phosphate [Na3 Ca6 (PO4 )5 ], beta-tricalcium phosphate [Ca3 (PO4 )] and
      amorphous silica were detected. In vitro cell culture studies were performed by
      evaluating proliferation, metabolic activity and differentiation of human
      osteoblast-like cells (MG63). Scaffolds made with cuttlefish bone powder
      exhibited increased apatite deposition, alkaline phosphatase activity and cell
      proliferation compared with commercial synthetic HAP. In addition, the ceramic
      compositions obtained after the combination with Bioglass(r) further enhanced the
      metabolic activity of MG63 cell and promoted the formation of a well-developed
      apatite layer after 7 days of incubation in Dulbecco's modified Eagle's medium.

PMID- 28500667
TI  - Magnetic resonance neurography and diffusion tensor imaging of the peripheral
      nerves in patients with Charcot-Marie-Tooth Type 1A.
AB  - INTRODUCTION: Investigation of peripheral neuropathies by magnetic resonance
      neurography (MRN) may provide increased diagnostic accuracy when performed in
      combination with diffusion tensor imaging (DTI). This study seeks to evaluate DTI
      in the detection of neuropathic abnormalities in Charcot-Marie-Tooth type 1A
      (CMT1A). METHODS: MRI of the sciatic and tibial nerves, including MRN and DTI,
      was prospectively performed in 15 CMT1A patients and 30 healthy controls (HCs).
      The following MRI parameters were evaluated and correlated with clinical and
      neurophysiological findings: T2-relaxation time, proton spin density (PD) and DTI
      (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]). RESULTS:
      DTI showed lower FA and higher ADC in CMT1A compared with HCs. T2 relaxation time
      showed no difference; however, PD of the sciatic nerve was higher in CMT1A. There
      were some close associations between neuropathy severity and MRN-DTI, with the
      closest correlation between FA and nerve conduction velocity in the sciatic nerve
      (r = 0.76, P < 0.01). DISCUSSION: MRN-DTI evaluation of sciatic and tibial nerves
      improves the detection of nerve abnormalities in patients with CMT1A. Muscle
      Nerve 56: E78-E84, 2017.

PMID- 28500668
TI  - Advanced multivariate data analysis to determine the root cause of trisulfide
      bond formation in a novel antibody-peptide fusion.
AB  - Product quality heterogeneities, such as a trisulfide bond (TSB) formation, can
      be influenced by multiple interacting process parameters. Identifying their root
      cause is a major challenge in biopharmaceutical production. To address this
      issue, this paper describes the novel application of advanced multivariate data
      analysis (MVDA) techniques to identify the process parameters influencing TSB
      formation in a novel recombinant antibody-peptide fusion expressed in mammalian
      cell culture. The screening dataset was generated with a high-throughput (HT)
      micro-bioreactor system (AmbrTM 15) using a design of experiments (DoE) approach.
      The complex dataset was firstly analyzed through the development of a multiple
      linear regression model focusing solely on the DoE inputs and identified the
      temperature, pH and initial nutrient feed day as important process parameters
      influencing this quality attribute. To further scrutinize the dataset, a partial
      least squares model was subsequently built incorporating both on-line and off
      line process parameters and enabled accurate predictions of the TSB concentration
      at harvest. Process parameters identified by the models to promote and suppress
      TSB formation were implemented on five 7 L bioreactors and the resultant TSB
      concentrations were comparable to the model predictions. This study demonstrates
      the ability of MVDA to enable predictions of the key performance drivers
      influencing TSB formation that are valid also upon scale-up. Biotechnol. Bioeng.
      2017;114: 2222-2234. (c) 2017 The Authors. Biotechnology and Bioengineering
      Published by Wiley Periodicals, Inc.

PMID- 28500669
TI  - Anti-Mullerian hormone signaling is influenced by Follistatin 288, but not 14
      other transforming growth factor beta superfamily regulators.
AB  - The hypothesis that, in contrast to other transforming growth factor-beta
      (TGFbeta) superfamily ligands, the dose-response curve of Anti-Mullerian hormone
      (AMH) is unmodulated was tested by examining whether known TGFB superfamily
      modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMHC
      and AMHN,C activated the reporter with an EC50 of approximately 0.5 nM.
      Follistatins (FS) produced concentration-dependent increases in AMHC - and AMHN,C
      -initiated reporter activity, with FS288 being more potent than FS315; however,
      the maximum bioactivity of AMH was not altered by either follistatin. Thirteen
      other TGFbeta regulators (Chordin, Chordin-like 1, Chordin-like 2, Differential
      screening-selected gene aberrative in neuroblastoma [DAN], Decorin, Endoglin,
      Follistatin-like 1, Follistatin-like 3, Follistatin-like 4, Noggin, alpha2
      macroglobulin, TGFbeta receptor 3, Von Willebrand factor C domain-containing 2)
      had little or no effect. Surface plasmon resonance analysis showed no significant
      association between FS288 and AMHC , suggesting that FS288 indirectly regulates
      AMH signaling. Activin A, a direct target of FS288, did not itself induce
      reporter activity in P19 cells, but did prevent the FS288-induced increase in AMH
      signaling. Hence, local concentrations of FS288 and Activin A may influence the
      response of some cell types to AMH.

PMID- 28500671
TI  - Is the firing rate of motor units in different vastus medialis regions modulated
      similarly during isometric contractions?
AB  - INTRODUCTION: Previous evidence suggests the fibers of different motor units
      reside within distinct vastus medialis (VM) regions. It remains unknown whether
      the activity of these motor units may be modulated differently. Herein we assess
      the discharge rate of motor units detected proximodistally from the VM to address
      this issue. METHODS: Surface electromyograms (EMGs) were recorded proximally and
      distally from the VM while 10 healthy subjects performed isometric contractions.
      Single motor units were decomposed from surface EMGs. The smoothed discharge
      rates of motor units identified from the same and from different VM regions were
      then cross-correlated. RESULTS: During low-level contractions, the discharge rate
      varied more similarly for distal (cross-correlation peak; interquartile interval:
      0.27-0.40) and proximal (0.28-0.52) than for proximodistal pairs of VM motor
      units (0.20-0.33; P = 0.006). DISCUSSION: The discharge rates of motor units from
      different proximodistal VM regions show less similarity in their variations than
      those of pairs of units either distally or proximally. Muscle Nerve 57: 279-286,
      2018.

PMID- 28500670
TI  - Coupled effects of salt and pressure on catalytic ability of Rhizopus chinensis
      lipase.
AB  - BACKGROUND: Both high pressure and environmental factors could influence the
      catalytic abilities of enzymes. This work investigated coupled effects of
      pressure and salts on Rhizopus chinensis lipase (RCL) to provide significant
      information for its further applications. RESULTS: The maximum activity of RCL
      was observed under 200 MPa at 40  degrees C. The highest activity was achieved at
      concentrations of 0.06-0.1 mol L-1 for tested salts. The effect of monovalent
      cations on RCL activity followed the Hofmeister series (K+ > Na+ > Li+ ) at 0.1
      MPa but the order of Na+ and K+ was changed under 200 MPa. Meanwhile, the effects
      of anions did not follow the Hofmeister series. KCl slightly improved the
      thermostability of RCL at moderate concentration. At 60  degrees C, LiCl only
      stabilised RCL at 0.1 mol L-1 . The pre-transition unfolding point was shifted
      from 4.5 to 3.5 mol L-1 with pressure increasing from 0.1 to 600 MPa. In
      addition, KCl could not change the lipase's extrinsic fluorescence evolution
      versus pressure. CONCLUSION: Pressure and salts could improve catalytic ability
      and stability of RCL under appropriate conditions. The effect of high pressure on
      RCL was influenced by salts. Meanwhile salts cannot prevent high pressure-induced
      damage to RCL. (c) 2017 Society of Chemical Industry.

PMID- 28500673
TI  - Uterine tissue aging and adverse reproductive outcomes: New concepts, mechanisms,
      and markers.

PMID- 28500672
TI  - Telomere length and fetal programming: A review of recent scientific advances.
AB  - We sought to synthesize a comprehensive literature review comprising recent
      research linking fetal programming to fetal telomere length. We also explored the
      potential effects fetal telomere length shortening has on fetal phenotypes.
      Utilizing the PubMed database as our primary search engine, we retrieved and
      reviewed 165 articles of published research. The inclusion criteria limited the
      articles to those that appeared within the last ten years, were pertinent to
      humans, and without restriction to language of publication. Our results showed
      that socio-demographic factors like age, sex, genetic inheritance, and acquired
      disease impact telomere length. Further, we found several maternal
      characteristics to be associated with fetal telomere length shortening, and these
      include maternal chemical exposure (eg, tobacco smoke), maternal stress during
      pregnancy, maternal nutritional and sleeping disorders during pregnancy as well
      as maternal disease status. Due to paucity of data, our review could not
      synthesize evidence directly linking fetal phenotypes to telomere length
      shortening. Although the research summarized in this review shows some
      association between determinants of intrauterine programming and fetal telomere
      length, there is still significant work that needs to be done to delineate the
      direct relationship of telomere attrition with specific fetal phenotypes.

PMID- 28500674
TI  - Disseminated cutaneous nocardiosis with ocular involvement.

PMID- 28500675
TI  - Counterfactual Plausibility and Comparative Similarity.
AB  - Counterfactual thinking involves imagining hypothetical alternatives to reality.
      Philosopher David Lewis (1973, 1979) argued that people estimate the subjective
      plausibility that a counterfactual event might have occurred by comparing an
      imagined possible world in which the counterfactual statement is true against the
      current, actual world in which the counterfactual statement is false.
      Accordingly, counterfactuals considered to be true in possible worlds
      comparatively more similar to ours are judged as more plausible than
      counterfactuals deemed true in possible worlds comparatively less similar.
      Although Lewis did not originally develop his notion of comparative similarity to
      be investigated as a psychological construct, this study builds upon his idea to
      empirically investigate comparative similarity as a possible psychological
      strategy for evaluating the perceived plausibility of counterfactual events. More
      specifically, we evaluate judgments of comparative similarity between episodic
      memories and episodic counterfactual events as a factor influencing people's
      judgments of plausibility in counterfactual simulations, and we also compare it
      against other factors thought to influence judgments of counterfactual
      plausibility, such as ease of simulation and prior simulation. Our results
      suggest that the greater the perceived similarity between the original memory and
      the episodic counterfactual event, the greater the perceived plausibility that
      the counterfactual event might have occurred. While similarity between actual and
      counterfactual events, ease of imagining, and prior simulation of the
      counterfactual event were all significantly related to counterfactual
      plausibility, comparative similarity best captured the variance in ratings of
      counterfactual plausibility. Implications for existing theories on the
      determinants of counterfactual plausibility are discussed.

PMID- 28500676
TI  - An evaluation of interdependent and independent group contingencies during the
      good behavior game.
AB  - The Good Behavior Game (GBG) uses an interdependent group contingency to improve
      classroom behavior. Despite the wealth of research on the effectiveness of the
      GBG, some teachers may have concerns about their students' abilities to work in
      teams, particularly if they have a history of poor social skills. We used an
      alternating treatments design to compare the relative effectiveness of the GBG
      with interdependent and independent group contingencies in a classroom for
      children with emotional and behavioral disorders. Our results showed that both
      versions of the GBG reduced verbal disruptions, inappropriate sitting, and off
      task behaviors for all children. However, the majority of children preferred the
      interdependent arrangement. We discuss how these results may promote more
      widespread use of the GBG with children with substantial behavioral challenges.

PMID- 28500678
TI  - BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 12
      week, randomized, double-blind, placebo-controlled, phase II dose-titration study
      with an open-label extension.
AB  - OBJECTIVES: To evaluate dose-response relationship of BGG492 as add-on therapy to
      1-3 antiepileptic drugs in patients with partial-onset seizures and to
      investigate safety and tolerability of BGG492. METHODS: This was a 12-week,
      randomized, double-blind, placebo-controlled, phase II dose-titration study (core
      study) with a 30-week, flexible-dose, open-label extension. In the core study,
      patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1,
      and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d.
      On completion of the core study, eligible patients entered the extension study.
      Primary outcome measures were total partial seizure frequency per 28 days (core
      study) and safety and tolerability (extension study). RESULTS: Overall, 93
      patients were randomized (150 mg [n = 44]; 100 mg [n = 24]; placebo [n = 25]),
      and 81 (87.1%) completed the core study. Fifty-one patients entered and 43
      (84.3%) completed the extension study. In the core study, no statistically
      significant dose-response trend among the BGG492 treatment groups (100 and 150
      mg) was observed at the 4-week double-blind maintenance period (weeks 7-10);
      however, there was higher percent reduction in total partial seizure frequency in
      the BGG492 150 mg over placebo groups (37.32%; 95% confidence interval [CI] 
      18.90, 66.95). Dizziness, somnolence, and fatigue were the most common adverse
      events (AEs), higher in the BGG492 150 mg group than in the 100 mg and placebo
      groups (dizziness: 14 [31.8%] vs. 3 [12.5%] and 1 [4.0%]; somnolence: 7 [15.9%]
      vs. 1 [4.2%] and 1 [4.0%]; fatigue: 5 [11.4%] vs. 1 [4.2%] and 1 [4.0%]). During
      the open-label extension study, 39 (76.5%) patients on BGG492 had AEs, and the
      most commonly experienced AEs were dizziness (14 [27.5%]) and somnolence (9
      [17.6%]). SIGNIFICANCE: There was no significant dose-response trend in the
      BGG492 treatment groups (100 and 150 mg); however, higher percent reduction over
      placebo was observed in the BGG492 150 mg group. Safety and tolerability data
      were consistent with the known safety profile for BGG492, and no new safety risks
      were identified.

PMID- 28500677
TI  - Optimizing the dose in cancer patients treated with imatinib, sunitinib and
      pazopanib.
AB  - AIM: Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib
      show a high interpatient variability in plasma exposure. A relationship between
      plasma exposure and treatment outcome has been established, which supports the
      rationale for dose optimization of these drugs. The aim of this study was to
      monitor how many patients reached adequate trough levels after therapeutic drug
      monitoring-based dose optimization in daily practice. METHODS: A cohort study was
      performed in patients treated with imatinib, sunitinib or pazopanib of whom
      follow-up drug levels were measured between August 2012 and April 2016. Patients'
      characteristics were collected by reviewing electronic patient records. Drug
      levels were measured using high-performance liquid chromatography coupled with
      tandem mass spectrometry and trough levels were estimated using a predefined
      algorithm. Dose interventions were proposed based on trough levels. RESULTS: In
      total, 396 trough levels were determined in 109 patients. Median sample frequency
      per patient was 3. During the first measurement only 38% of patients showed
      trough levels within the predefined target ranges despite standard dosing; 52% of
      the patients showed drug levels below and 10% above the target range. In 35 out
      of 41 patients (85%) dose interventions led to adequate trough levels.
      Eventually, 64% of the total cohort reached adequate trough levels. CONCLUSIONS:
      Dose optimization proved an effective tool to reach adequate trough levels in
      patients treated with imatinib, sunitinib and pazopanib. The percentage of
      patients with adequate trough levels increased from 38 to 64%. Therapeutic drug
      monitoring may add to the improvement of efficacy and reduction of toxicity and
      costs of these treatments.

PMID- 28500679
TI  - Red tattoos, ultraviolet radiation and skin cancer in mice.
AB  - Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red
      tattoos may be associated with increased risk of skin cancer due to potential
      carcinogens in tattoo inks. This combination has not been studied previously.
      Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back
      with a popular red tattoo ink. This often used ink is banned for use on humans
      because of high content of the potential carcinogen 2-anisidine. Half of the mice
      were irradiated with three standard erythema doses UVR thrice weekly. Time to
      induction of first, second and third squamous cell carcinoma (SCC) was measured.
      All UV-irradiated mice developed SCCs. The time to the onset of the first and
      second tumor was identical in the red-tattooed group compared with the control
      group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor
      appeared slightly faster in the red-tattooed group than in the controls (214 vs
      224 days, P=.043). For the second and third tumor, the growth rate was faster in
      the red-tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs
      38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin
      tattooed with a red ink containing 2-anisidine. However, red tattoos exposed to
      UVR showed faster tumor onset regarding the third tumor, and faster growth rate
      of the second and third tumor indicating red ink acts as a cocarcinogen with UVR.
      The cocarcinogenic effect was weak and may not be clinically relevant.

PMID- 28500680
TI  - Rapid detoxification via glutathione S-transferase (GST) conjugation confers a
      high level of atrazine resistance in Palmer amaranth (Amaranthus palmeri).
AB  - BACKGROUND: Palmer amaranth (Amaranthus palmeri) is an economically troublesome,
      aggressive and damaging weed that has evolved resistance to six herbicide modes
      of action including photosystem II (PS II) inhibitors such as atrazine. The
      objective of this study was to investigate the mechanism and inheritance of
      atrazine resistance in Palmer amaranth. RESULTS: A population of Palmer amaranth
      from Kansas (KSR) had a high level (160 - 198-fold more; SE +/-21 - 26) of
      resistance to atrazine compared to the two known susceptible populations MSS and
      KSS, from Mississippi and Kansas, respectively. Sequence analysis of the
      chloroplastic psbA gene did not reveal any known mutations conferring resistance
      to PS II inhibitors, including the most common Ser264Gly substitution for
      triazine resistance. However, the KSR plants rapidly conjugated atrazine at least
      24 times faster than MSS via glutathione S-transferase (GST) activity.
      Furthermore, genetic analyses of progeny generated from reciprocal crosses of KSR
      and MSS demonstrate that atrazine resistance in Palmer amaranth is a nuclear
      trait. CONCLUSION: Although triazine resistance in Palmer amaranth was reported
      more than 20 years ago in the USA, this is the first report elucidating the
      underlying mechanism of resistance to atrazine. The non-target-site based
      metabolic resistance to atrazine mediated by GST activity may predispose the
      Palmer amaranth populations to have resistance to other herbicide families, and
      the nuclear inheritance of the trait in this dioecious species further
      exacerbates the propensity for its rapid spread. (c) 2017 Society of Chemical
      Industry.

PMID- 28500681
TI  - Comparison of Time to First Dose of Oral Morphine in the Treatment of Neonatal
      Abstinence Syndrome.
AB  - OBJECTIVE: To compare time to first dose of oral morphine used in the treatment
      of neonatal abstinence syndrome (NAS) in a neonatal intensive care unit (NICU)
      versus a special care nursery (SCN) setting. METHODS: A retrospective chart
      review was completed of patient data from two community hospitals in a single
      health network. Infants born at either facility between January 2013 and August
      2015 were eligible for inclusion in the study if treated for NAS with a course of
      oral morphine. The primary outcome was time from birth to first dose of oral
      morphine. Secondary outcomes included details about the morphine treatment
      course, length of stay, and complications from NAS. RESULTS: A total of 54
      patients (19 NICU patients and 35 SCN patients) fulfilled inclusion criteria for
      the study. The primary outcome of median time from birth to first dose of oral
      morphine did not differ between the two groups (42.5 hrs [NICU] vs 43 hrs [SCN],
      p=0.53). No significant differences were found between the morphine regimens used
      in the two units. The median length of hospital stay (27 days [NICU] vs 26 days
      [SCN], p=0.66) and median length of NICU/SCN stay (26 days [NICU] vs 23 days
      [SCN], p=0.75) were not statistically significantly different. Time between
      transfer to the NICU or SCN and administration of the first dose of oral morphine
      was significantly shorter in the SCN setting (28 hrs [NICU] vs 4 hrs [SCN],
      p=0.009). CONCLUSIONS: This study found that infants treated for NAS had similar
      treatment in an NICU and an SCN. No difference was observed in time from birth to
      initiation of medication therapy. In addition, no differences were seen in all
      but one marker for quality of care including length of stay and cumulative
      morphine dose. Infants treated for NAS, whether in an NICU or SCN setting, can
      receive similar treatment and comparable outcomes.

PMID- 28500682
TI  - Red blood cell transfusions during sickle cell anemia vaso-occlusive crises: a
      report from the magnesium in crisis (MAGiC) study.
AB  - BACKGROUND: Little is known about red blood cell (RBC) transfusion practices for
      children hospitalized for a sickle cell vaso-occlusive pain crisis (VOC). We
      hypothesized that transfusion would be associated with the development of acute
      chest syndrome (ACS), lower hemoglobin (Hb) concentration, and lack of
      hydroxyurea therapy. STUDY DESIGN AND METHODS: This is a secondary analysis of
      all children admitted for a sickle cell pain crisis enrolled in the Magnesium in
      Crisis (MAGiC) randomized trial; all had HbSS or S-beta0 thalassemia. ACS
      development and transfusion administration were prospectively collected during
      the parent trial. All Hb values during the hospitalization were recorded, as was
      parent report of child receiving hydroxyurea. Relative risks (RRs) of transfusion
      were compared between groups. RESULTS: Of 204 enrolled children, 40 (19.6%)
      received a transfusion. Of the 30 children who developed ACS, 22 (73.3%) received
      transfusions compared to 18 of 174 (10.3%) without ACS: the RR of transfusion in
      children with ACS was 7.1 (95% confidence interval [CI], 4.4-11.5). Among those
      without ACS, the lowest Hb was most strongly associated with transfusions: RR was
      3.1 (95% CI 2.0 - 4.7) for each 1 g/dL decrease in lowest Hb. In a binary
      recursive partitioning model for those without ACS, a lowest recorded Hb level of
      less than 6.3 g/dL was significantly associated with transfusion during admission
      (p < 0.01). Hydroxyurea use was not associated with transfusions in any analysis.
      CONCLUSION: ACS increased the RR of transfusion in children hospitalized for VOC
      sevenfold. In children without ACS, transfusion was associated with lowest Hb
      concentration, particularly Hb concentration of less than 6.3 g/dL.

PMID- 28500683
TI  - Induction of telomere-mediated chromosomal truncation and behavior of truncated
      chromosomes in Brassica napus.
AB  - Engineered minichromosomes could be stably inherited and serve as a platform for
      simultaneously transferring and stably expressing multiple genes. Chromosomal
      truncation mediated by repeats of telomeric sequences is a promising approach for
      the generation of minichromosomes. In the present work, direct repetitive
      sequences of Arabidopsis telomere were used to study telomere-mediated truncation
      of chromosomes in Brassica napus. Transgenes containing alien Arabidopsis
      telomere were successfully obtained, and Southern blotting and fluorescence in
      situ hybridization (FISH) results show that the transgenes resulted in successful
      chromosomal truncation in B. napus. In addition, truncated chromosomes were
      inherited at rates lower than that predicted by Mendelian rules. To determine the
      potential manipulations and applications of the engineered chromosomes, such as
      the stacking of multiple transgenes and the Cre/lox and FRT/FLP recombination
      systems, both amenable to genetic manipulations through site-specific
      recombination in somatic cells, were tested for their ability to undergo
      recombination in B. napus. These results demonstrate that alien Arabidopsis
      telomere is able to mediate chromosomal truncation in B. napus. This technology
      would be feasible for chromosomal engineering and for studies on chromosome
      structure and function in B. napus.

PMID- 28500685
TI  - Analysis of serum markers of cellular immune activation in patients with bullous
      pemphigoid.
AB  - Experimental models of bullous pemphigoid (BP), the most frequent subepidermal
      autoimmune bullous disease, revealed that the immune response leading to blister
      formation represents an incompletely understood complex process involving
      different inflammatory cells. In contrast to previous reports commonly focusing
      on limited molecular and cellular phenotypes of the disease, the aim of this
      study was to investigate a broad spectrum of markers of cellular immune
      activation in patients with BP. We found that serum levels of soluble CD4,
      myeloperoxidase, S100A12, eosinophil cationic protein and soluble P-selectin were
      significantly elevated in patients with active BP compared with normal controls.
      Mast cell tryptase and neopterin serum levels significantly decreased at the time
      of clinical remission of the patients. Additionally, serum concentrations of
      soluble IL-2 receptor, mast cell tryptase and soluble P-selectin were
      significantly associated with levels of circulating anti-BP180 autoantibodies.
      Our findings confirm and extend previous reports suggesting some concomitant
      involvement of a panel of molecules representative for a wide spectrum of
      cellular players (T cells, mast cells, neutrophils, eosinophils, macrophages and
      platelets) orchestrating the inflammatory reaction in BP. These data may favour
      the employment of broad-spectrum or combined immunosuppressants, potentially
      together with an anticoagulant treatment, over cell- or molecule-specific
      targeted therapy in patients with this disorder.

PMID- 28500684
TI  - Impact of Roux-en-Y gastric bypass surgery on appetite, alcohol intake behaviors,
      and midbrain ghrelin signaling in the rat.
AB  - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) surgery reduces appetite and
      stimulates new onset alcohol misuse; however, the genesis of these behavioral
      changes is unclear. This study is hypothesized that new onset alcohol intake is a
      behavioral adaptation that occurs secondary to reduced appetite and correlates
      with altered central ghrelin signaling. METHODS: Hedonic high-fat diet (HFD)
      intake was evaluated prior to the assessment of alcohol intake behaviors in RYGB
      and control rats. Measurements were also taken of circulating ghrelin and ghrelin
      receptor (GHSR) regulation of neuronal firing in ventral tegmental area (VTA)
      dopamine (DA) neurons. RESULTS: RYGB rats displayed reduced HFD intake relative
      to controls. Sham and RYGB rats consumed more alcohol and preferred lower
      concentrations of alcohol, whereas only RYGB rats escalated alcohol intake during
      acute withdrawal. Remarkably, GHSR activity, independent of peripheral ghrelin
      release, set the tonic firing of VTA DA neurons, a response selectively
      diminished in RYGB rats. CONCLUSIONS: This study indicates that gut manipulations
      lead to increased alcohol intake, whereas RYGB promotes behaviors that may
      maintain alcohol misuse. Reductions in hedonic feeding and diminished GHSR
      control of VTA firing further distinguish gut manipulation from complete bypass
      and present a potential mechanism linking reduced appetite with alcohol misuse
      after RYGB surgery.

PMID- 28500686
TI  - Factors predicting overall response and overall survival in hepatocellular
      carcinoma patients undergoing balloon-occluded transcatheter arterial
      chemoembolization: A retrospective cohort study.
AB  - AIM: This study aimed to investigate the factors predicting overall response and
      overall survival in hepatocellular carcinoma patients undergoing balloon-occluded
      transcatheter arterial chemoembolization (B-TACE). METHODS: Sixty-six patients
      treated with B-TACE at a Japanese tertiary referral hospital between January 2011
      and August 2015 were included in this retrospective cohort study. RESULTS: The
      overall response was classified as complete response, partial response, stable
      disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11
      (16.7%) patients, respectively. The response rate was 63.6%, and the disease
      control rate was 83.3%. The number of tumors (hazard ratio [HR], 4.44; 95%
      confidence interval [CI], 1.26-15.7; P = 0.021) and alpha-fetoprotein level (HR,
      11.40; 95% CI, 2.75-46.9; P < 0.001) were significantly associated with the tumor
      response in a multivariate analysis. The 1-, 2-, and 3-year survival rates were
      76.8% (95% CI, 64.5-85.3%), 57.3% (95% CI, 42.3-69.7%), and 46.7% (95% CI, 30.7
      61.2%), respectively. The median survival time was 902 days. Albumin (>=3.4 g/dL)
      (HR, 0.28; 95% CI, 0.12-0.63; P = 0.002) and overall response (complete response
      and partial response) (HR, 0.33; 95% CI, 0.16-0.71; P = 0.004) were factors
      significantly associated with overall survival in a multivariate analysis. No
      mortalities were observed, but biloma requiring percutaneous transhepatic biliary
      drainage occurred in one patient (1.5%). CONCLUSION: Balloon-occluded
      transcatheter arterial chemoembolization may exert a good antitumor effect and
      result in good overall survival in select hepatocellular carcinoma patients.

PMID- 28500687
TI  - Epidemiological analysis and follow-up of human rhinovirus infection in children
      with asthma exacerbation.
AB  - To determine the prevalence of human rhinovirus (HRV) infection in children with
      acute asthma exacerbations, investigation of HRV viral load and severity of
      asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were
      collected and assessed for respiratory viruses. HRV-positive samples were
      sequenced to identify types and determine viral load. Outpatients with asthma
      exacerbations underwent follow-up evaluations, their swabs were collected and
      clinical outcomes were recorded at their next clinic visit 4 weeks later. One
      hundred forty-three inpatients and 131 outpatients, including 88 patients with
      asthma exacerbations and 43 controls with stable asthma were recruited. HRV-A was
      mainly detected in September and February (45.5% and 33.3%, respectively), while
      HRV-C was mainly detected in November and April (70.0% and 55.6%, respectively).
      HRV-C was the primary type and was primarily found in inpatients with severe
      asthma exacerbations. HRV-A viral load in the group of inpatients with severe
      exacerbations was higher than in the mild and moderate groups (P < 0.001 and P =
      0.022). The HRV-A viral load of both inpatients and outpatients was higher than
      that of HRV-C (P < 0.001 and P = 0.036). The main genotypes were HRV-C53 and HRV
      A20 among inpatients, and this genotype caused more severe clinical
      manifestations. HRV persisted for no more than 4 weeks, and their symptoms or
      signs of disease were well-controlled well. HRV-C was most frequently detected in
      asthma exacerbations. HRV-A with high viral load led to severe asthma
      exacerbations.

PMID- 28500688
TI  - Fennel (Foeniculum vulgare Mill. subsp. piperitum) florets, a traditional
      culinary spice in Italy: evaluation of phenolics and volatiles in local
      populations, and comparison with the composition of other plant parts.
AB  - BACKGROUND: Wild fennel (Foeniculum vulgare Mill. subsp. piperitum) florets are
      used as a typical spice in central and southern Italy. Although fennel
      (Foeniculum vulgare Mill.), belonging to the Apiaceae (syn. Umbelliferae) family,
      is a well-known vegetable and aromatic plant, whose main phytochemical compounds
      have been extensively analysed and investigated as flavouring agents and for
      their putative health promoting functions, its florets have not been specifically
      considered up to now. Therefore, the volatile and phenolic composition of florets
      from an Italian wild fennel crop was determined at different developmental
      stages, and compared to that of leaves and fruits. Moreover, florets of nine
      Italian wild fennel populations of different geographical origin from northern
      central Italy were also analysed. RESULTS: The total phenolic amount increased
      from leaves to florets, reaching its highest value in early florets, at 58 012 mg
      kg-1 of dry matter (DM), then constantly decreased in fruits. In florets of wild
      populations, phenolics ranged from 6666 to 43 368 mg kg-1 DM. The total amount of
      volatile compounds was more than twice higher in florets (21 449 mg kg-1 DM) than
      in leaves (10 470 mg kg-1 DM), reaching its highest value in fruits (50 533 mg kg
      1 DM). Estragole and trans-anethole were the main compounds of the volatile
      fraction. Total volatiles ranged from 24 367 to 60 468 mg kg-1 DM in florets of
      local populations. CONCLUSION: Significant changes in the total amount and
      profile of both phenolic and volatile compounds occurred during plant
      development. The consistent increase of estragole at later developmental stages
      supported the claim of different sensory properties of florets and fruits.
      Geographical origin significantly affected phenolic and volatile composition of
      wild fennel florets. (c) 2017 Society of Chemical Industry.

PMID- 28500690
TI  - Tumour necrosis factor receptor-associated periodic syndrome mimicking chronic
      spontaneous urticaria.

PMID- 28500689
TI  - Blockade of hedgehog pathway is required for the protective effects of magnesium
      isoglycyrrhizinate against ethanol-induced hepatocyte steatosis and apoptosis.
AB  - Alcoholic liver disease (ALD), characterized by excessive deposition of lipids in
      hepatocytes, causes heavy health burden personally and socially. Mechanistically,
      hedgehog signaling was activated during the development of ALD, and exerted
      compelling role in regulating lipometabolism. The current promising intervention
      strategy is inhibition of lipid accumulation and apoptosis in hepatocytes.
      Magnesium isoglycyrrhizinate (MgIG) has been widely used in various liver
      diseases for its good hepatoprotective activities. However, the role of MgIG in
      ALD has not been elucidated. Therefore, this study was aimed to explore the role
      of MgIG and further identify the potential mechanisms. We found for the first
      time that MgIG reduced lipid accumulation, including triglyceride, and total
      cholesterol, probably via inducing peroxisome proliferator-activated receptor
      alpha and inhibiting sterol regulatory element-binding protein-1c. Further, MgIG
      alleviated ethanol-induced oxidative stress, evidenced by reduced abundance of
      reactive oxygen species and increased levels of glutathione, superoxide
      dismutase, and mitochondrial transmembrane potential. Besides, MgIG protected
      hepatocytes from ethanol-induced apoptosis. In addition, MgIG dose-dependently
      suppressed hedgehog signaling. Of note was that disruption of hedgehog signaling
      could mimic the effects of MgIG, whereas activation of hedgehog signaling
      abrogated the effects of MgIG. These findings suggested that MgIG prevented
      ethanol-induced hepatocyte steatosis and apoptosis via a hedgehog signaling
      inhibition-dependent mechanism. (c) 2017 IUBMB Life, 69(7):540-552, 2017.

PMID- 28500691
TI  - An Interventional Study Using Cell-Mediated Immunity to Personalize Therapy for
      Cytomegalovirus Infection After Transplantation.
AB  - Cell-mediated immune responses predict clinical cytomegalovirus (CMV) events but
      have not been adopted into routine practice due to lack of interventional
      studies. Our objective was to demonstrate the safety and feasibility of early
      discontinuation of antivirals based on the real-time measurement of CMV-specific
      cell-mediated immunity (CMI) in patients with CMV viremia. Transplant patients
      were enrolled at the onset of CMV viremia requiring antiviral therapy. CD8 T cell
      responses were determined using the Quantiferon-CMV assay, and results were used
      to guide subsequent management. A total of 27 patients (median viral load at
      onset 10 900 International Units/mL) were treated until viral load negative. At
      end of treatment, 14/27 (51.9%) had a positive CMV-CMI response and had
      antivirals discontinued. The remaining 13/27 (48.1%) patients had a negative CMV
      CMI response and received 2 months of secondary antiviral prophylaxis. In those
      with a positive CMI and early discontinuation of antivirals, only a single
      patient experienced a low-level asymptomatic recurrence. In contrast, recurrence
      was observed in 69.2% of CMI-negative patients despite more prolonged antivirals
      (p = 0.001). In conclusion, this is the first study to demonstrate the
      feasibility and safety of real-time CMV-specific CMI assessment to guide changes
      to the management of CMV infection.

PMID- 28500693
TI  - The clinical spectrum of xanthomatous lesions of the eyelids.
AB  - Yellowish papules, nodules, or plaques, namely "xanthomatous" lesions, may be
      seen on the eyelids in the course of various disorders. The prototype is
      "xanthelasma palpebrarum" (XP) that is localized only to the eyelids and may be
      associated with hyperlipidemia. On the other hand, different types of
      normolipemic disorders may also cause xanthomatous eyelid lesions. Among these,
      Langerhans cell histiocytosis, diffuse normolipemic xanthoma, and non-Langerhans
      cell histiocytoses (papular xanthoma, juvenile xanthogranuloma, xanthoma
      disseminatum, adult-onset xanthogranuloma, adult-onset asthma and periocular
      xanthogranuloma, necrobiotic xanthogranuloma, Erdheim-Chester disease, Rosai
      Dorfman disease, and reticulohistiocytosis) can be listed. The eyelid findings of
      this heterogeneous group of disorders are challenging to differentiate from each
      other due to common clinical aspects that may even sometimes mimic XP.
      Nodularity, induration, ulceration, diffuse eyelid involvement, and extension
      from eyelids to the neighboring skin may represent the clinical features of
      xanthomatous lesions other than XP. It is necessary to obtain a thorough history
      and exclude XP and then perform detailed dermatological and systemic examination,
      biopsy for histopathologic confirmation, and appropriate specific imaging
      screens. As some of the conditions may be associated with other systemic
      disorders, especially malignancies, the differentiation of xanthomatous eyelid
      lesions has a critical importance, and clinical signs can be guiding.

PMID- 28500692
TI  - Toll-like receptor 4 mediates fat, sugar, and umami taste preference and food
      intake and body weight regulation.
AB  - OBJECTIVE: Immune and inflammatory pathways play important roles in the
      pathogenesis of metabolic disorders. This study investigated the role of toll
      like receptor 4 (TLR4) in orosensory detection of dietary lipids and sugars.
      METHODS: Taste preferences of TLR4 knockout (KO) and wild-type (WT) male mice
      under a standard and a high-fat, high-sugar diet were assessed with two-bottle
      tests. Gene expression of taste signaling molecules was analyzed in the tongue
      epithelium. The role of TLR4 in food intake and weight gain was investigated in
      TLR4 KO and WT mice fed a high-fat and high-sugar diet for 12 weeks. RESULTS:
      Compared to WT mice, TLR4 KO mice showed reduced preference for lipids, sugars,
      and umami in a two-bottle preference test. The altered taste perception was
      associated with decreased levels of key taste regulatory molecules in the tongue
      epithelium. TLR4 KO mice on a high-fat and high-sugar diet consumed less food and
      drink, resulting in diminished weight gain. CONCLUSIONS: TLR4 signaling promotes
      ingestion of sugar and fat by a mechanism involving increased preference for such
      obesogenic foods.

PMID- 28500694
TI  - Trends of Neonatal Abstinence Syndrome Epidemic and Maternal Risk Factors in
      Florida.
AB  - OBJECTIVE: This study aimed to examine secular trends of (i) maternal
      prescription opioid use in late pregnancy, (ii) neonatal abstinence syndrome
      (NAS) stratified by late maternal prescription opioid use, and (iii) maternal
      risk factors among NAS deliveries. METHODS: Women with a live birth who were
      enrolled 90 days before and 30 days after delivery in Florida Medicaid Analytic
      Extract billing records linked to birth certificates from 2000 to 2010 were
      identified for the study. Changes in the annual prevalence of prescription opioid
      use during pregnancy were tested with use of the Cochran-Armitage trend test.
      Temporal trends of NAS deliveries were estimated with the use of Poisson
      regression and stratified by prescription opioid exposure in the last 90 days of
      pregnancy in the study period. To identify contributors to the increase in NAS
      cases, variations in prevalence of opioid dispensing, tobacco use, antidepressant
      use, and substance use disorder among NAS and non-NAS deliveries were examined.
      RESULTS: There were 41,968 (9.4%) deliveries exposed to at least one opioid
      prescription in late pregnancy, and this rate remained stable from 2000 to 2010.
      Among prescription opioid-exposed deliveries, frequency of NAS increased from 1.6
      to 25.2 per 1000 live births during the study period (p<0.05). Although the
      prevalence of maternal use of prescription opioid, tobacco, and antidepressants
      remained stable among NAS deliveries from 2000 to 2010, the prevalence of
      substance use disorder diagnoses increased substantially from 38.9% in 2000 to
      67.9% in 2006 (p<0.05). CONCLUSIONS: The prevalence of NAS increased dramatically
      whereas the prevalence of major risk factors, including maternal prescription
      opioid use, remained stable in Florida between 2000 and 2010. The increase in
      substance use disorder may be responsible for the sharp increase in NAS
      deliveries.

PMID- 28500696
TI  - A Simple Preparation Method for Phytochromobilin.
AB  - Phytochromobilin (PPhiB), the chromophore of plant phytochromes, is difficult to
      isolate because phytochromes occur at very low concentrations in plants. It is,
      therefore, frequently replaced in plant phytochrome studies by phycocyanobilin,
      which is abundant in cyanobacteria. PPhiB is also an attractive chromophore for
      far-red emitting chromoproteins. In this work, we design and optimize a simple
      method to efficiently isolate useful quantities of PPhiB: The chromophore is
      generated in Escherichia coli and transiently bound to a tailored chromophore
      binding domain of ApcE2, the apo-protein of a core-membrane linker, from which it
      can subsequently be released. The ease and effectiveness of this method hinges
      not only on the enhanced biosynthesis of PPhiB in the presence of the ApcE2
      construct from Synechococcus sp. PCC7335, but also on the noncovalent binding of
      the pigment to its apo-protein. The isolated PPhiB was successfully incorporated
      into phytochrome-related assemblies, and furthermore, the noncovalently bound
      PPhiB could be transferred directly from the ApcE2 construct to the apo-proteins
      of phytochromes, cyanobacteriochromes and phycobiliproteins, without loss of
      relevant biological activity.

PMID- 28500695
TI  - Clinical characteristics and survival of systemic sclerosis patients with
      pulmonary hypertension and elevated wedge pressure: Observations from the PHAROS
      cohort.
AB  - BACKGROUND AND OBJECTIVE: Systemic sclerosis (SSc) is a complex autoimmune
      disease commonly associated with pulmonary hypertension (PH). When associated
      with elevated pulmonary artery wedge pressure (PAWP), pulmonary artery pressure
      (PAP) is either in-proportion (post-capillary PH) or higher than expected
      (combined PH) relative to the increased PAWP. METHODS: Patients from the PHAROS
      registry (a prospective observational cohort of SSc-PH patients) who had mean PAP
      >= 25 and PAWP > 15 on right heart catheterization were stratified based on
      diastolic pressure gradient (DPG). Kaplan-Meier analysis was performed to compare
      survival and PH-related hospitalization. Baseline factors were compared between
      patients dying and those who survived using Cox regression analysis. RESULTS: A
      total of 59 patients were included, of whom 21 (36%) patients were classified as
      combined PH and 38 (64%) had post-capillary PH. No baseline characteristics were
      significantly different between the two groups. There were no differences in
      survival or PH-related hospitalization between the groups. The only baseline
      factor independently associated with death was lower 6-min walk distance (6MWD)
      (hazard ratio (HR): 1.33 per 25 m decrease, 95% CI: 1.11-1.59, P = 0.002). PH
      specific medications were started during follow-up in significantly more patients
      in the combined PH group compared with the post-capillary group (86% vs 50%, P =
      0.01). CONCLUSION: Outcomes were similar between SSc patients with post-capillary
      PH and combined pre- and post-capillary PH. 6MWD at baseline can predict risk for
      death in SSc patients with PH and an elevated PAWP. More patients with combined
      PH were started on PH-specific medications, and the clinical benefit of treating
      this subgroup specifically in SSc patients needs further exploration.

PMID- 28500697
TI  - Light-Induced Conformational Changes in the Plant Cryptochrome Photolyase
      Homology Region Resolved by Selective Isotope Labeling and Infrared Spectroscopy.
AB  - Plant cryptochromes are photoreceptors that regulate flowering, circadian rhythm
      and photomorphogenesis in response to blue and UV-A light. It has been
      demonstrated that the oxidized flavin cofactor is photoreduced to the neutral
      radical state via separate electron and proton transfer. Conformational changes
      have been found in the C-terminal extension, but few studies have addressed the
      changes in secondary structure in the sensory photolyase homology region (PHR).
      Here, we investigated the PHR of the plant cryptochrome from the green alga
      Chlamydomonas reinhardtii by light-induced infrared difference spectroscopy in
      combination with global 13 C and 15 N isotope labeling. Assignment of the signals
      is achieved by establishing a labeling strategy for cryptochromes that preserves
      the flavin at natural abundance. We demonstrate by UV/vis spectroscopy that the
      integrity of the sample is maintained and by mass spectrometry that the global
      labeling was highly efficient. As a result, difference bands are resolved at full
      intensity that at natural abundance are compensated by the overlap of flavin and
      protein signals. These bands are assigned to prominent conformational changes in
      the PHR by blue light illumination. We postulate that not only the partial
      unfolding of the C-terminal extension but also changes in the PHR may mediate
      signaling events.

PMID- 28500698
TI  - Phytochromes from Agrobacterium fabrum.
AB  - Agrobacterium fabrum is a widely used model bacterium for gene transfer from pro-
      to eukaryote, for genetics and metabolism. The phytochrome system of
      Agrobacterium, encompassing the two phytochromes Agp1 and Agp2, has provided deep
      insight into phytochrome action in a bacterial organism. This review summarizes
      recent results on phytochrome evolution, phytochrome regulation of conjugation
      and plant infection and biochemical studies including the crystal structure of
      Agp1-PCM, the photosensory core module of Agp1.

PMID- 28500699
TI  - Distinctive Properties of Dark Reversion Kinetics between Two Red/Green-Type
      Cyanobacteriochromes and their Application in the Photoregulation of cAMP
      Synthesis.
AB  - Cyanobacteriochromes (CBCRs) are photoreceptors that bind to a linear
      tetrapyrrole within a conserved cGMP-phosphodiesterase/adenylate cyclase/FhlA
      (GAF) domain and exhibit reversible photoconversion. Red/green-type CBCR GAF
      domains that photoconvert between red- (Pr) and green-absorbing (Pg) forms occur
      widely in various cyanobacteria. A putative phototaxis regulator, AnPixJ,
      contains multiple red/green-type CBCR GAF domains. We previously reported that
      AnPixJ's second domain (AnPixJg2) but not its fourth domain (AnPixJg4) shows
      red/green reversible photoconversion. Herein, we found that AnPixJg4 showed Pr-to
      Pg photoconversion and rapid Pg-to-Pr dark reversion, whereas AnPixJg2 showed a
      barely detectable dark reversion. Site-directed mutagenesis revealed the
      involvement of six residues in Pg stability. Replacement at the Leu294/Ile660
      positions of AnPixJg2/AnPixJg4 showed the highest influence on dark reversion
      kinetics. AnPixJg2_DR6, wherein the six residues of AnPixJg2 were entirely
      replaced with those of AnPixJg4, showed a 300-fold faster dark reversion than
      that of the wild type. We constructed chimeric proteins by fusing the GAF domains
      with adenylate cyclase catalytic regions, such as AnPixJg2-AC, AnPixJg4-AC and
      AnPixJg2_DR6-AC. We detected successful enzymatic activation under red light for
      both AnPixJg2-AC and AnPixJg2_DR6-AC, and repression under green light for
      AnPixJg2-AC and under dark incubation for AnPixJg2_DR6-AC. These results provide
      platforms to develop cAMP synthetic optogenetic tools.

PMID- 28500701
TI  - Editorial (2017, issue 3).

PMID- 28500700
TI  - Influence of Heterogeneity on the Ultrafast Photoisomerization Dynamics of Pfr in
      Cph1 Phytochrome.
AB  - Photoisomerization of a protein-bound chromophore is the basis of light sensing
      and signaling in many photoreceptors. Phytochrome photoreceptors can be
      photoconverted reversibly between the Pr and Pfr states through
      photoisomerization of the methine bridge between rings C and D. Ground-state
      heterogeneity of the chromophore has been reported for both Pr and Pfr. Here, we
      report ultrafast visible (Vis) pump-probe and femtosecond polarization-resolved
      Vis pump-infrared (IR) probe studies of the Pfr photoreaction in native and 13
      C/15 N-labeled Cph1 phytochrome with unlabeled PCB chromophore, demonstrating
      different S0 substates, Pfr-I and Pfr-II, with distinct IR absorptions,
      orientations and dynamics of the carbonyl vibration of ring D. We derived time
      constants of 0.24 ps, 0.7 ps and 6 ps, describing the complete initial
      photoreaction. We identified an isomerizing pathway with 0.7 ps for Pfr-I, and
      silent dynamics with 6 ps for Pfr-II. We discuss different origins of the Pfr
      substates, and favor different facial orientations of ring D. The model provides
      a quantum yield for Pfr-I of 38%, in line with ~35% ring D rotation in the
      electronic excited state. We tentatively assign the silent form Pfr-II to a dark
      adapted state that can convert to Pfr-I upon light absorption.

PMID- 28500702
TI  - Bacterial Photosensory Proteins and Their Role in Plant-pathogen Interactions.
AB  - Light is an important environmental signal for almost all living organisms. The
      light perception is achieved by photoreceptor proteins. As can be observed from
      the great number of bacterial genomes sequenced, plant pathogenic bacteria encode
      for a large number of photoreceptor proteins. The physiological implications of
      these photoreceptors are still poorly characterized. However, recent studies
      revealed the participation of these photosensory proteins in the pathogenic
      process. Here, we summarize what is known about these proteins and their role
      during the virulence process, concluding that the light environment modulates the
      plant-pathogen interaction.

PMID- 28500703
TI  - Excitation Energies of Canonical Nucleobases Computed by Multiconfigurational
      Perturbation Theories.
AB  - In this computational work, we assessed the performance of ab initio
      multireference (MR) methods for the calculation of vertical excitation energies
      of five nucleobases: adenine, guanine, cytosine, thymine and uracil. In total, we
      have studied 38 singlet and 30 triplet excited states. Where possible we used the
      multireference configuration interaction (MRCI) method as a reference for various
      flavors of multireference perturbation theory to second order. In particular, we
      have benchmarked CASPT2, NEVPT2 and XMCQDPT2. For CASPT2, we have analyzed the
      single-state, multistate (MS) and extended MS variants. In addition, we have
      assessed the effect of the ionization potential electron affinity (IPEA) shift.
      For NEVPT2, we have used the partially and the strongly contracted variants.
      Further, we have tested the commonly used RI-CC2, RI-ADC2 and EOM-CCSD methods.
      Generally, we observe the following trends for singlet excited states: NEVPT2 is
      the closest MR method to MRCISD+Q, closely followed by CASPT2 with the default
      IPEA shift. The same trend is observed for triplet states, although NEVPT2 and
      CASPT2-IPEA are getting closer. Interestingly, the n, pi* singlet excited states
      were described more accurately than pi, pi* excited states, while for triplet
      states the trend is inverted except for NEVPT2. This work is an important
      benchmark for future photochemical investigations.

PMID- 28500704
TI  - Meta-Analysis of the Transcriptome Reveals a Core Set of Shade-Avoidance Genes in
      Arabidopsis.
AB  - The presence of neighboring vegetation modifies the light input perceived by
      photo-sensory receptors, initiating a signaling cascade that adjusts plant growth
      and physiology. Thousands of genes can change their expression during this
      process, but the structure of the transcriptional circuit is poorly understood.
      Here we present a meta-analysis of transcriptome data from Arabidopsis thaliana
      exposed to neighbor signals in different contexts, including organs where growth
      is promoted or inhibited by these signals. We identified a small set of genes
      that consistently and dynamically respond to neighbor light signals. This group
      is also affected by light during de-etiolation and day/night cycles. Among these
      genes, many of those with positive response to neighbor signals are binding
      targets of PHYTOCHROME-INTERACTING FACTORS (PIFs) and function as transcriptional
      regulators themselves, but none of these features is observed among those with
      negative response to neighbor signals. Changes. in neighbor signals can mimic the
      transcriptional signature of auxin, gibberellins, brassinosteroid, abscisic acid,
      ethylene, jasmonic acid and cytokinin but in a context-dependent manner. We
      propose the existence of a small core set of genes involved in downstream
      communication of PIF signaling status and in the control of light sensitivity and
      chloroplast metabolism.

PMID- 28500705
TI  - Integration of Temperature and Blue-Light Sensing in Acinetobacter baumannii
      Through the BlsA Sensor.
AB  - BlsA is a BLUF photoreceptor present in Acinetobacter baumannii, responsible for
      modulation of motility, biofilm formation and virulence by light. In this work,
      we have combined physiological and biophysical evidences to begin to understand
      the basis of the differential photoregulation observed as a function of
      temperature. Indeed, we show that blsA expression is reduced at 37 degrees C,
      which correlates with negligible photoreceptor levels in the cells, likely
      accounting for absence of photoregulation at this temperature. Another point of
      control occurs on the functionality of the BlsA photocycle itself at different
      temperatures, which occurs with an average quantum yield of photoactivation of
      the signaling state of 0.20 +/- 0.03 at 15 degrees C < T < 25 degrees C, but is
      practically inoperative at T > 30 degrees C, as a result of conformational
      changes produced in the nanocavity of FAD. This effect would be important when
      the photoreceptor is already present in the cell to avoid almost instantaneously
      further signaling process when it is no longer necessary, for example under
      circumstances of temperature changes possibly faced by the bacteria. This complex
      interplay between light and temperature would provide the bacteria clues of
      environmental location and dictate/modulate light photosensing in A. baumannii.

PMID- 28500706
TI  - Common Structural Elements in the Chromophore Binding Pocket of the Pfr State of
      Bathy Phytochromes.
AB  - Phytochromes are bimodal photoreceptors which, upon light absorption by the
      tetrapyrrole chromophore, can be converted between a red-absorbing state (Pr) and
      far-red-absorbing state (Pfr). In bacterial phytochromes, either Pr or Pfr are
      the thermally stable states, thereby constituting the classes of prototypical and
      bathy phytochromes, respectively. In this work, we have employed vibrational
      spectroscopies to elucidate the origin of the thermal stability of the Pfr states
      in bathy phytochromes. Here, we present the first detailed spectroscopic analysis
      of RpBphP6 (Rhodopseudomas palustris), which together with results obtained for
      Agp2 (Agrobacterium tumefaciens) and PaBphP (Pseudomonas aeruginosa) allows
      identifying common structural properties of the Pfr state of bathy phytochromes,
      which are (1) a homogenous chromophore structure, (2) the protonated ring C
      propionic side chain of the chromophore and (3) a retarded H/D exchange at the
      ring D nitrogen. These properties are related to the unique strength of the
      hydrogen bonding interactions between the ring D N-H group with the side chain of
      the conserved Asp194 (PaBphP numbering). As revealed by a comparative analysis of
      homology models and available crystal structures of Pfr states, these
      interactions are strengthened by an Arg residue (Arg453) only in bathy but not in
      prototypical phytochromes.

PMID- 28500707
TI  - Introduction, Festschrift in honor of Wolfgang Gartner.

PMID- 28500708
TI  - Proteorhodopsin Photocycle Kinetics Between pH 5 and pH 9.
AB  - The retinal protein proteorhodopsin is a homolog of the well-characterized light
      driven proton pump bacteriorhodopsin. Basic mechanisms of proton transport seem
      to be conserved, but there are noticeable differences in the pH ranges of proton
      transport. Proton transport and protonation state of a carboxylic acid side
      chain, the primary proton acceptor, are correlated. In case of proteorhodopsin,
      the pKa of the primary proton acceptor Asp-97 (pKa  ~ 7.5) is unexpectedly close
      to environmental pH (pH ~ 8). A significant fraction of proteorhodopsin is
      possibly inactive at natural pH, in contrast to bacteriorhodopsin. We
      investigated photoinduced kinetics of proteorhodopsin between pH 5 and pH 9 by
      time resolved UV/vis absorption spectroscopy. Kinetics is inhomogeneous within
      that pH region and can be considered as a superposition of two fractions. These
      fractions are correlated with the Asp-97 titration curve. Beside Asp-97,
      protonation equilibria of other groups influence kinetics, but the observations
      do not point toward major differences of primary proton acceptor function in
      proteorhodopsin and bacteriorhodopsin. The pKa of proteorhodopsin and some of its
      variants is suspected to be an example of molecular adaptation to the physiology
      of the original organisms.

PMID- 28500709
TI  - The Expanded Red/Green Cyanobacteriochrome Lineage: An Evolutionary Hot Spot.
AB  - This article highlights the paper by Rockwell et al. in the current issue of
      Photochemistry and Photobiology. Rockwell et al. describe the discovery of novel
      two-Cys photocycles within the "expanded red/green" (XRG) cyanobacteriochrome
      (CBCR) lineage. Comprehensive phylogenetic analysis revealed that several XRG
      CBCRs possess a second Cys residue in the DXCF (Asp-Xaa-Cys-Phe) motif conserved
      among the DXCF CBCR lineage. Spectral studies identified that these CBCRs showed
      green/blue or ultraviolet/blue reversible photoconversion abilities. The
      green/blue reversible photocycle had not been reported previously among the XRG
      CBCR lineage. Based on these findings, Rockwell et al. replaced three amino acid
      residues in a red/green reversible CBCR, NpR6012g4, and succeeded in constructing
      a violet/green reversible photocycle. These findings, together with previous
      studies, provide a good explanation for the evolutionary flexibility of the XRG
      CBCRs.

PMID- 28500710
TI  - Characterization of the Blue-Light-Activated Adenylyl Cyclase mPAC by Flash
      Photolysis and FTIR Spectroscopy.
AB  - The recently discovered photo-activated adenylyl cyclase (mPAC from Microcoleus
      chthonoplastes) is the first PAC that owes a light-, oxygen- and voltage
      sensitive (LOV) domain for blue-light sensing. The photoreaction of the mPAC
      receptor was studied by time-resolved UV/vis and light-induced Fourier transform
      infrared (FTIR) absorption difference spectroscopy. The photocycle comprises of
      the typical triplet state LOV715 and the thio-adduct state LOV390 . While the
      adduct state decays with a time constant of 8 s, the lifetime of the triplet
      state is with 656 ns significantly shorter than in all other reported LOV
      domains. The light-induced FTIR difference spectrum shows the typical bands of
      the LOV390 and LOV450 intermediates. The negative S-H stretching vibration at
      2573 cm-1 is asymmetric suggesting two rotamer configurations of the protonated
      side chain of C194. A positive band at 3632 cm-1 is observed, which is assigned
      to an internal water molecule. In contrast to other LOV domains, mPAC exhibits a
      second positive feature at 3674 cm-1 which is due to the O-H stretch of a second
      intrinsic water molecule and the side chain of Y476. We conclude that the latter
      might be involved in the dimerization of the cyclase domain which is crucial for
      ATP binding.

PMID- 28500711
TI  - Quantum Chemical Spin Densities for Radical Cations of Photosynthetic Pigment
      Models.
AB  - The spin densities of radical cations of magnesium porphyrin, magnesium chlorine
      and a truncated chlorophyll a model are calculated with density-functional theory
      and multiconfigurational quantum chemical methods. The latter serve as a
      reference for approximate density-functional theory which yields spin densities
      that may suffer from the self-interaction error. We carried out complete active
      space self-consistent field calculations with increasing active orbital spaces to
      systematically converge qualitatively correct spin densities. In particular, for
      the magnesium chlorine and chlorophyll a model radical cations, this is not easy
      to achieve because of the lower symmetry compared to magnesium porphyrin.
      Strategies had to be employed which allowed us to consider very large active
      orbital spaces. We explored restricted active space self-consistent field and
      density-matrix renormalization group calculations. Based on these reference data,
      we assessed the accuracy of different density-functional approximations. We show
      that in particular, exchange-correlation model potentials with correct asymptotic
      behavior yield good spin densities, and we find, in agreement with previous
      studies on different classes of compounds, that hybrid functionals systematically
      increase spin-polarization effects with increasing amounts of exact exchange. Our
      results provide a starting point for investigations of spin densities of more
      complex systems such as the hinge model for the primary electron donor in
      photosystem II.

PMID- 28500712
TI  - Time-Resolved Energetics of Photoprocesses in Prokaryotic Phytochrome-Related
      Photoreceptors.
AB  - Time-resolved photoacoustics (PA) is uniquely able to explore the energy
      landscape of photoactive proteins and concomitantly detects light-induced
      volumetric changes (DeltaV) accompanying the formation and decay of transient
      species in a time window between ca. 20 ns and 5 MUs. Here, we report PA
      measurements on diverse photochromic bilin-binding photoreceptors of prokaryotic
      origin: (1) the chromophore-binding GAF3 domain of the red (R)/green (G)
      switching cyanobacteriochrome 1393 (Slr1393g3) from Synechocystis; (2) the
      red/far red (R/FR) Synechocystis Cph1 phytochrome; (3) full-length and truncated
      constructs of Xanthomonas campestris bacteriophytochrome (XccBphP), absorbing up
      to the NIR spectral region. In almost all cases, photoisomerization results in a
      large fraction of energy dissipated as heat (up to 90%) on the sub-ns scale,
      reflecting the low photoisomerization quantum yield (<0.2). This "prompt" step is
      accompanied by a positive DeltaV1  = 5-12.5 mL mol-1 . Formation of the first
      intermediate is the sole process accessible to PA, with the notable exception of
      Slr1393g3-G for which DeltaV1  = +4.5 mL mol-1 is followed by a time-resolved,
      energy-conserving contraction DeltaV2  = -11.4 mL mol-1 , tau2  = 180 ns at 2.4
      degrees C. This peculiarity is possibly due to a larger solvent occupancy of the
      chromophore cavity for Slr1393g3-G.

PMID- 28500713
TI  - Photochemical Properties of the Red-shifted Channelrhodopsin Chrimson.
AB  - Color-tuned variants of channelrhodopsins allow for selective optogenetic
      manipulation of different host cell populations. Chrimson is the channelrhodopsin
      with the longest wavelength absorbance maximum. We characterize its photochemical
      properties at different pH values corresponding to two protonation states of the
      counterion for the protonated Schiff base. Both states will lead to a functional
      channel opening, but the route is different as reflected in the photochemical
      states observed spectroscopically. The light-induced isomerization kinetics
      change with the local electrostatic environment, becoming faster with the
      presence of an anionic counterion. The spectral effect is stronger on the ground
      state energy surface. From the excited state, a bifurcated pathway leads to the
      electronic ground state resulting in a pronounced excitation wavelength
      dependence. The subsequent steps in the photocycles at pH 6 and pH 9.5 differ in
      the accumulation of states with a protonated and deprotonated Schiff base,
      respectively, that can be correlated with the open channel. Therefore, different
      protonation states are preserved in the open and the initial states. Chrimson's
      photocycle at alkaline pH shows features observed in other rhodopsins without an
      internal proton donor to the Schiff base, but it accumulates an intermediate with
      an even longer lifetime reflecting slow recovery of the initial state.

PMID- 28500714
TI  - Sensory Rhodopsin I and Sensory Rhodopsin II Form Trimers of Dimers in Complex
      with their Cognate Transducers.
AB  - Archaeal photoreceptors consist of sensory rhodopsins in complex with their
      cognate transducers. After light excitation, a two-component signaling chain is
      activated, which is homologous to the chemotactic signaling cascades in
      enterobacteria. The latter system has been studied in detail. From structural and
      functional studies, a picture emerges which includes stable signaling complexes,
      which assemble to receptor arrays displaying hexagonal structural elements. At
      this higher order structural level, signal amplification and sensory adaptation
      occur. Here, we describe electron microscopy data, which show that also the
      archaeal phototaxis receptors sensory rhodopsin I and II in complex with their
      cognate transducers can form hexagonal lattices even in the presence of a
      detergent. This result could be confirmed by molecular dynamics calculations,
      which revealed similar structural elements. Calculations of the global modes of
      motion displayed one mode, which resembles the "U"-"V" transition of the
      NpSRII:NpHtrII complex, which was previously argued to represent a functionally
      relevant global conformational change accompanying the activation process
      [Ishchenko et al. (2013) J. Photochem. Photobiol. B 123, 55-58]. A model of
      cooperativity at the transmembrane level is discussed.

PMID- 28500715
TI  - Crystal Effects on Mesobilirubin: A Combined NMR Spectroscopic and Density
      Functional Theory Study.
AB  - We report solid-state NMR investigations of crystal effects in powdered
      mesobilirubin-IXalpha, an open-chain tetrapyrrole that is structurally related to
      bilirubin-IXalpha but hydrogenated at the 3- and 18-vinyl groups. 13 C and 15 N
      cross-polarization magic-angle spinning (CP/MAS) NMR experiments were performed
      on the compound at natural abundance. To facilitate the spectral analysis,
      density functional calculations were carried out at the B3LYP/6-311G(d,p) level
      of theory, using an enneameric cluster to simulate the solid. The 1 H, 13 C and
      15 N chemical shift data calculated for the enneamer are in a good agreement with
      those observed in the experimental spectra, and the relative order of the
      calculated resonances was thus used to confirm the tentative assignments obtained
      mainly from the heteronuclear correlation spectra. The observed signal splittings
      of a small subset of the 13 C resonances in the peripheral regions of the two
      terminal rings provide evidence for microcrystalline heterogeneity of the
      powdered compound.

PMID- 28500716
TI  - Functional Expression of Gloeobacter Rhodopsin in Synechocystis sp. PCC6803.
AB  - Proteorhodopsins are light-driven proton pumps that occur widespread in Nature,
      where they function predominantly in environments with high incident irradiance.
      Their maximal absorbance is usually in the blue range, but can be extended into
      the (far)red range of the electromagnetic spectrum. Because they can be expressed
      heterologously, they may be exploited in studies aimed at increasing the
      efficiency of photosynthesis. Here we report further studies toward this goal, by
      comparing the expression of two different bacterial rhodopsins (Proteorhodopsin
      and Gloeobacter rhodopsin) in the model cyanobacterium Synechocystis sp. PCC6803.
      In particular, we investigated the pigments bound by the respective apo-opsins,
      and the oligomeric state of the corresponding holo-rhodopsins, both in
      Escherichia coli and in the cyanobacterial membranes. We conclude that the two
      proton-pumping rhodopsins are predominantly present in an oligomeric state
      (hexamers for Proteorhodopsin and trimers for Gloeobacter rhodopsin).
      Furthermore, Gloeobacter rhodopsin is able to bind an antenna carotenoid (in
      addition to retinal) and has the highest pumping rate at given light intensity.
      However, its lower expression level will decrease its physiological
      effectiveness. It remains to be established which of these two bacterial
      rhodopsins is best in stimulating the growth rate of its cyanobacterial host.

PMID- 28500717
TI  - Epigenetically Enhanced Photodynamic Therapy (ePDT) is Superior to Conventional
      Photodynamic Therapy for Inducing Apoptosis in Cutaneous T-Cell Lymphoma.

PMID- 28500718
TI  - RPE65 and the Accumulation of Retinyl Esters in Mouse Retinal Pigment Epithelium.
AB  - The RPE65 protein of the retinal pigment epithelium (RPE) enables the conversion
      of retinyl esters to the visual pigment chromophore 11-cis retinal. Fresh 11-cis
      retinal is generated from retinyl esters following photoisomerization of the
      visual pigment chromophore to all-trans during light detection. Large amounts of
      esters accumulate in Rpe65-/- mice, indicating their continuous formation when 11
      cis retinal generation is blocked. We hypothesized that absence of light, by
      limiting the conversion of esters to 11-cis retinal, would also result in the
      build-up of retinyl esters in the RPE of wild-type mice. We used HPLC to quantify
      ester levels in organic extracts of the RPE from wild-type and Rpe65-/- mice.
      Retinyl ester levels in Sv/129 wild-type mice that were dark adapted for various
      intervals over a 4-week period were similar to those in mice raised in cyclic
      light. In C57BL/6 mice however, which contain less Rpe65 protein, dark adaptation
      was accompanied by an increase in ester levels compared to cyclic light controls.
      Retinyl ester levels were much higher in Rpe65-/- mice compared to wild type and
      kept increasing with age. The results suggest that the RPE65 role in retinyl
      ester homeostasis extends beyond enabling the formation of 11-cis retinal.

PMID- 28500719
TI  - Novel Thermostable Flavin-binding Fluorescent Proteins from Thermophilic
      Organisms.
AB  - Flavin-binding fluorescent proteins (FbFPs) are small, oxygen-independent in vivo
      reporters, derived from Light Oxygen Voltage (LOV) domains of photoreceptors.
      Here, we investigated the thermostability of existing, as well as novel FbFPs,
      whose genes were identified in genome sequences of various thermophilic bacteria
      as well as metagenomic libraries from hot springs in the Yellowstone National
      Park. Detailed in vitro analyses revealed that two of those fluorescent reporter
      proteins were highly thermostable, exhibiting melting temperatures above 75
      degrees C.

PMID- 28500720
TI  - Casting Away the Shadows: Elucidating the Role of Light-mediated
      Posttranscriptional Control in Plants.
AB  - Light signals trigger precise changes in gene expression networks that activate
      distinctive developmental programs in plants. The transcriptome is shaped at
      different stages, both by the regulation of gene expression and also by
      posttranscriptional mechanisms that alter the sequence or abundance of the
      transcripts generated. Posttranscriptional mechanisms have attracted much
      interest in recent years with the advent of high-throughput technologies and
      bioinformatics tools. One such posttranscriptional process, alternative splicing,
      increases proteome diversity without increasing gene number by changing the
      function of individual proteins, while another, miRNA-mediated gene silencing,
      fine-tunes the amount of mRNA produced. The manner in which plants make use of
      these two crucial posttranscriptional mechanisms to respond to light and adapt to
      their environment is the focus of active research. In this review, we summarize
      the current knowledge of light-mediated posttranscriptional control in
      Arabidopsis thaliana and focus on the biological impact of the various
      posttranscriptional processes. We also discuss a potential cross talk between the
      alternative splicing and miRNA pathways, highlighting the complexity of light
      responsiveness.

PMID- 28500721
TI  - Structural and Vibrational Characterization of the Chromophore Binding Site of
      Bacterial Phytochrome Agp1.
AB  - Agp1 is a prototypical bacterial phytochrome from Agrobacterium fabrum harboring
      a biliverdin cofactor which reversibly photoconverts between a red-light
      absorbing (Pr) and a far-red-light-absorbing (Pfr) states. The reaction mechanism
      involves the isomerization of the bilin-chromophore followed by large structural
      changes of the protein matrix that are coupled to protonation dynamics at the
      chromophore binding site. Histidines His250 and His280 participate in this
      process. Although the three-dimensional structure of Agp1 has been solved at high
      resolution, the precise position of hydrogen atoms and protonation pattern in the
      chromophore binding pocket has not been investigated yet. Here, we present
      protonated structure models of Agp1 in the Pr state involving appropriately
      placed hydrogen atoms that were generated by hybrid quantum mechanics/molecular
      mechanics- and electrostatic calculations and validated against experimental
      structural- and spectroscopic data. Although the effect of histidine protonation
      on the vibrational spectra is weak, our results favor charge neutral H250 and
      H280 both protonated at Nepsilon. However, a neutral H250 with a proton at
      Nepsilon and a cationic H280 may also be possible. Furthermore, the present QM/MM
      calculations of IR and Raman spectra of Agp1 containing isotope-labeled BV
      provide a detailed vibrational assignment of the biliverdin modes in the
      fingerprint region.

PMID- 28500722
TI  - UV-Resistant Actinobacteria from High-Altitude Andean Lakes: Isolation,
      Characterization and Antagonistic Activities.
AB  - Polyextremophiles are present in a wide variety of extreme environments in which
      they must overcome various hostile conditions simultaneously such as high UVB
      radiation, extreme pHs and temperatures, elevated salt and heavy-metal
      concentration, low-oxygen pressure and scarce nutrients. High-altitude Andean
      lakes (HAALs; between 2000 and 4000 m) are one example of these kinds of
      ecosystems suffering from the highest total solar and UVB radiation on Earth
      where an abundant and diverse polyextremophilic microbiota was reported. In this
      work, we performed the first extensive isolation of UV-resistant actinobacteria
      from soils, water, sediments and modern stromatolites at HAALs. Based on the 16S
      rRNA sequence, the strains were identified as members of the genera Streptomyces,
      Micrococcus, Nesterenkonia, Rhodococcus, Microbacterium, Kocuria, Arthrobacter,
      Micromonospora, Blastococcus, Citrococcus and Brevibacterium. Most isolates
      displayed resistance to multiple environmental stress factors confirming their
      polyextremophilic nature and were able to produce effective antimicrobial
      compounds. HAALs constitute a largely unexplored repository of UV-resistant
      actinobacteria, with high potential for the biodiscovery of novel natural
      products.

PMID- 28500723
TI  - Self-limited membranous glomerulonephritis due to syphilis.

PMID- 28500725
TI  - Study Break: Misconduct in Research and Publication: a Dilemma That Is Taking
      Place

PMID- 28500724
TI  - Grape seed proanthocyanidin extract ameliorates inflammation and adiposity by
      modulating gut microbiota in high-fat diet mice.
AB  - SCOPE: Obesity and associated metabolic complications is a worldwide public
      health issue. Gut microbiota have been recently linked to obesity and its related
      inflammation. In this study, we have explored the anti-inflammatory effect of
      grape seed proanthocyanindin extract (GSPE) in the high-fat diet (HFD)-induced
      obesity and identified the contribution of the gut microbiota to GSPE effects on
      metabolism. METHODS AND RESULTS: Mice were fed a normal diet and a high-fat diet
      with or without GSPE (300 mg/kg body weight/day) by oral gavage for 7 weeks.
      Supplementation with GSPE significantly decreased plasma levels of inflammatory
      factors such as TNF-alpha, IL-6 and MCP-1, companied with ameliorated macrophage
      infiltration in epidydimal fat and liver tissues. Furthermore, GSPE also reduced
      epidydimal fat mass and improved insulin sensitivity. 16S rDNA analyses revealed
      that GSPE supplementation modulated the gut microbiota composition and certain
      bacteria including Clostridium XIVa, Roseburia and Prevotella. More importantly,
      depleting gut microbiota by antibiotics treatment abolished the beneficial
      effects of GSPE on inflammation and adiposity. CONCLUSION: Our study identifies
      the novel links between gut microbiota alterations and metabolic benefits by GSPE
      supplementation, providing possibilities for the prevention and treatment of
      metabolic disorders by targeting gut microbiota through a potential prebiotic
      agent GSPE.

PMID- 28500726
TI  - Mutations associated with drug resistance and prevalence of vaccine escape
      mutations in patients with chronic hepatitis B infection.
AB  - The Brazilian public health system (SUS) has provided antiviral drugs for chronic
      hepatitis B treatment for over 10 years, but a system for monitoring for drug
      related resistance mutations is not available. Determine the presence of HBV
      mutations associated with resistance to nucleos(t)ide analogs among 81 patients
      with chronic HBV infection in Salvador-BA-Brazil. HBV-DNA was PCR amplified with
      primers deduced from the rt domain at the HBV P gene, the sequence extended 1032
      bp (from amino acid 1 to 344-rt domain). Those sequences were submitted to the
      HBV drug resistance database to retrieve each mutation according to the genotype.
      HBV genotype A1 (85.2%) was the most prevalent, followed by genotype A2 (4.9%), F
      (6.2%), and C1, D2, and D4 (1.2% each). Six patients (7%) exhibited resistance
      mutations to LAM, ETV, and TDF: two with patterns L180M + M204V and four with
      other different patterns: L80I + L180M + M204I; L80V + L180M + M204V; M204I;
      A194T. All of these mutations were present in patients with genotype A (four A1
      and two A2). In addition, four mutations in gene S (three cases with the sI195M
      mutation and one with the W196L mutation), were detected, corresponding to a rate
      of 6% of vaccine escape mutations. Althougth the small sample size, an
      association was found between the occurrence of HBV resistance mutations and
      HBeAg positivity, co-infection with HIV and a history of treatment for HBV and/or
      HIV.

PMID- 28500728
TI  - Immunolocalization of Substance P and NK-1 Receptor in ADIPOSE Stem Cells.
AB  - Substance P (SP) is a neuropeptide belonging to the thachykinin peptide family.
      SP, after binding to its receptor, the neurokinin 1 receptor (NK1R), controls
      several transcription factors such as NF-kappaB, hypoxia inducible factor (HIF
      1alpha), c-myc, c-fos, c-jun, and AP-1. SP and NK1R have a widespread
      distribution in both the central and peripheral nervous systems. They are also
      present in cells not belonging to the nervous system (immune cells, placenta,
      etc.). SP is located in all body fluids, that is, blood, cerebrospinal fluid,
      etc., making it ubiquitous throughout the human body. SP and NK1R genes are
      expressed in the stem cell line TF-1 and in primary stem cells derived from human
      placental cord blood. However, to our knowledge, the presence of SP and the NK1R
      receptor in adipose stem cells (ADSC) is unknown. We demonstrated by
      immunofluorescence the localization of SP and NK1R in human and rat ADSC. SP and
      NK1R are located in both the cytoplasm and the nucleus of these cells. The NK1R
      is higher in the nucleus than in the cytoplasm of ADSCs. By Western blot we
      demonstrated the presence of different isoforms of NK1R that have different
      subcellular locations in the ADSC. SP induces proliferation and mitogenesis
      through NK1R in ADSCs. These findings reported here for the first time suggest an
      important role for a SP/NK1R system, either as genetic and/or epigenetic factor,
      in both the cytoplasm and nucleus functions of the ADSCs. J. Cell. Biochem. 118:
      4686-4696, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28500729
TI  - Electrophilic Activation of Iodonium Ylides by Halogen-Bond-Donor Catalysis for
      Cross-Enolate Coupling.
AB  - The umpolung alkylation of silyl enol ethers with an iodonium(III) ylide proceeds
      under mild conditions to afford various 1,4-dicarbonyl compounds in high yields
      in the presence of a halogen-bonding catalyst. Unlike typical transition-metal
      activation processes of such ylide precursors, which tend to proceed via
      carbenoid intermediates, experimental and computational studies indicate that
      halogen bonding (XB) between the XB donor catalyst and the iodonium ylide plays a
      crucial role in promoting the reaction. The identification of a compatible
      Bronsted base catalyst enabled the extension of this method to enols generated in
      situ to give the corresponding adducts in good yields.

PMID- 28500727
TI  - Biological function and histone recognition of family IV bromodomain-containing
      proteins.
AB  - Bromodomain proteins function as epigenetic readers that recognize acetylated
      histone tails to facilitate the transcription of target genes. There are
      approximately 60 known human bromodomains, which are divided into eight sub
      families based on structural conservation. The bromodomain-containing proteins in
      family IV include seven members (BRPF1, BRPF2, BRPF3, BRD7, BRD9, ATAD2, and
      ATAD2b). The bromodomains of each of these proteins recognize and bind
      acetyllysine residues on histone tails protruding from the nucleosome. However,
      the histone marks recognized by each bromodomain protein can be very different.
      The BRPF1 subunit of the MOZ histone acetyltransferase (HAT) recognizes
      acetylated histones H2AK5ac, H4K12ac, H3K14ac, H4K8ac, and H4K5ac. While the
      bromodomain of BRD7, a member of the SWI/SNF complex, was shown to preferentially
      recognize acetylated histones H3K9ac, H3K14ac, H4K8ac, H4K12ac, and H4K16ac. The
      bromodomains of BRPF2 and BRPF3 have similar sequences, and function as part of
      the HBO1 HAT complex, but there is limited data on which histone ligands they
      bind. Similarly, there is little known about the histone targets of the BRD9 and
      ATAD2b bromodomain proteins. Interestingly, the ATAD2 bromodomain was recently
      shown to preferentially bind to the di-acetylated H4K5acK12ac mark found in newly
      synthesized histones following DNA replication. However, despite the
      physiological importance of the family IV bromodomains, little is known about how
      they function at the molecular or atomic level. In this review, we summarize our
      understanding of how family IV bromodomains recognize and select for acetyllysine
      marks and discuss the importance of acetylated histone recognition for their
      biological functions.

PMID- 28500730
TI  - Comparative prognostic value of postprocedural creatine kinase myocardial band
      and high-sensitivity troponin T in patients with non-ST-segment elevation
      myocardial infarction undergoing percutaneous coronary intervention.
AB  - OBJECTIVES: We aimed to assess the prognostic value of postprocedural creatine
      kinase myocardial band (CK-MB) and cardiac troponin (cTn) in patients with non-ST
      segment elevation myocardial infarction (NSTEMI). BACKGROUND: Whether
      postprocedural CK-MB or cTn is a better biomarker to stratify the risk after
      percutaneous coronary intervention (PCI) remains unknown. METHODS: This study
      included 2,077 patients with NSTEMI undergoing early PCI. Peak postprocedural
      values of CK-MB and high-sensitivity cTn T (hs-cTnT) were analyzed. The primary
      outcome was 3-year mortality. RESULTS: The median values of peak postprocedural
      CK-MB and hs-cTnT were 18.3 U L-1 and 0.140 ug L-1 , respectively. Overall, 211
      patients died during follow-up. There were 129 deaths in patients with CK-MB >the
      median value and 82 deaths in those with CK-MB <=the median value (Kaplan-Meier
      estimates of 3-year mortality, 18.9% and 14.0%, respectively; hazard ratio [HR] =
      1.52, 95% confidence interval [CI] 1.16-2.01; P < 0.001). There were 134 deaths
      in patients with hs-cTnT >the median value and 77 deaths in patients with hs-cTnT
      <=the median value (Kaplan-Meier estimates of 3-year mortality, 19.9% and 13.2%,
      respectively; HR = 1.90 [1.44-2.52]; P < 0.001). After adjustment, peak
      postprocedural CK-MB (adjusted HR = 1.05 [1.02-1.07], P < 0.001 for each 24 U L-1
      increment) and hs-cTnT (adjusted HR = 1.12 [1.01-1.25], P = 0.037 for each unit
      higher log hs-cTnT) remained independently associated with the risk of 3-year
      mortality. The C-statistic(s) of the model with CK-MB and hs-cTnT were 0.789
      [0.757-0.817] and 0.793 [0.762-0.821], respectively (P = 0.585). CONCLUSION: In
      patients with NSTEMI undergoing early PCI, peak postprocedural CK-MB and hs-cTnT
      are independently associated with the risk of 3-year mortality. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28500731
TI  - Alternative plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester, for
      blood containers with protective effects on red blood cells and improved cold
      resistance.
AB  - Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl
      chloride (PVC), is eluted from PVC-made blood containers and protects against red
      blood cell (RBC) hemolysis. However, concerns have arisen regarding the
      reproductive and developmental risks of DEHP in humans, and the use of
      alternative plasticizers for medical devices has been recommended worldwide. In
      this study, we propose that the use of a novel plasticizer, 4-cyclohexene-1,2
      dicarboxylic acid dinonyl ester (DL9TH), could help produce more useful and safe
      blood containers. PVC sheet containing DL9TH and di (2-ethylhexyl) 4-cyclohexene
      1,2-dicarboxylate (DOTH) provides comparable or superior protective effects to
      RBCs relative to PVC sheet containing DEHP or di-isononyl-cyclohexane-1,2
      dicarboxylate (DINCH(r) , an alternative plasticizer that has been used in PVC
      sheets for blood containers). The total amount of plasticizer eluted from
      DOTH/DL9TH-PVC sheets is nearly the same as that eluted from DEHP-PVC sheets. In
      addition, DOTH/DL9TH-PVC has better cold resistance than DEHP- and DINCH(r) -PVC
      sheets. In vitro and in vivo tests for biological safety based on International
      Organization for Standardization guidelines (10993 series) suggest that the
      DOTH/DL9TH-PVC sheet can be used safely. Subchronic toxicity testing of DL9TH in
      male rats in accordance with the principles of Organisation for Economic Co
      operation and Development Test Guideline 408 showed that DL9TH did not induce
      adverse effects up to the highest dose level tested (717 mg/kg body weight/day).
      There were no effects on testicular histopathology and sperm counts, and no
      indications of endocrine effects: testosterone, thyroid-stimulating hormone,
      follicle-stimulating hormone, and 17beta-estradiol were unchanged by the
      treatment, compared with the control group. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 106B: 1052-1063, 2018.

PMID- 28500732
TI  - Costs of cancer care in children and adolescents in Ontario, Canada.
AB  - BACKGROUND: Cancer in children and adolescents presents unique issues regarding
      treatment and survivorship, but few studies have measured economic burden. We
      estimated health care costs by phase of cancer care, from the public payer
      perspective, in population-based cohorts. METHODS: Children newly diagnosed at
      ages 0 days-14.9 years and adolescents newly diagnosed at 15-19.9 years, from
      January 1, 1995 to June 30, 2010, were identified from Ontario cancer registries,
      and each matched to three noncancer controls. Data were linked with
      administrative records describing resource use for cancer and other health care.
      Total and net (patients minus controls) resource-specific costs ($CAD2012) were
      estimated using generalized estimating equations for four phases of care:
      prediagnosis (60 days), initial (360 days), continuing (variable), final (360
      days). RESULTS: Mean ages at diagnosis were 6 years for children (N = 4,606) and
      17 years for adolescents (N = 2,443). Mean net prediagnosis phase 60-day costs
      were $6,177 for children and $1,018 for adolescents. Costs for initial,
      continuing, and final phases were $138,161, $15,756, and $316,303 per 360 days
      for children, and $62,919, $7,071, and $242,008 for adolescents. The highest
      initial phase costs were for leukemia patients ($156,225 per 360 days for
      children and $171,275 for adolescents). The final phase was the most costly
      ($316,303 per 360 days for children and $242,008 for adolescents). CONCLUSIONS:
      Costs for children with cancer are much higher than for adolescents and much
      higher than those reported in adults. Comprehensive population-based long-term
      estimates of cancer costs are useful for health services planning and cost
      effectiveness analysis.

PMID- 28500733
TI  - Bordetella effector BopN is translocated into host cells via its N-terminal
      residues.
AB  - Bordetella bronchiseptica infects a wide variety of mammals, the type III
      secretion system (T3SS) being involved in long-term colonization by Bordetella of
      the trachea and lung. T3SS translocates virulence factors (commonly referred to
      as effectors) into host cells, leading to alterations in the host's physiological
      function. The Bordetella effectors BopN and BteA are known to have roles in up
      regulation of IL-10 and cytotoxicity, respectively. Nevertheless, the mechanism
      by which BopN is translocated into host cells has not been examined in sufficient
      detail. Therefore, to determine the precise mechanisms of translocation of BopN
      into host cells, truncated derivatives of BopN were built and the derivatives'
      ability to translocate into host cells evaluated by adenylate cyclase-mediated
      translocation assay. It was found that N-terminal amino acid (aa) residues 1-200
      of BopN are sufficient for its translocation into host cells. Interestingly, BopN
      translocation was completely blocked by deletion of the N-terminal aa residues 6
      50, indicating that the N-terminal region is critical for BopN translocation.
      Furthermore, BopN appears to play an auxiliary role in BteA-mediated
      cytotoxicity. Thus, BopN can apparently translocate into host cells and may
      facilitate activity of BteA.

PMID- 28500734
TI  - Differentiation of human olfactory bulb-derived neural stem cells toward
      oligodendrocyte.
AB  - In the central nervous system (CNS), oligodendrocytes are the glial element in
      charge of myelin formation. Obtaining an overall presence of oligodendrocyte
      precursor cells/oligodendrocytes (OPCs/OLs) in culture from different sources of
      NSCs is an important research area, because OPCs/OLs may provide a promising
      therapeutic strategy for diseases affecting myelination of axons. The present
      study was designed to differentiate human olfactory bulb NSCs (OBNSCs) into
      OPCs/OLs and using expression profiling (RT-qPCR) gene, immunocytochemistry, and
      specific protein expression to highlight molecular mechanism(s) underlying
      differentiation of human OBNSCs into OPCs/OLs. The differentiation of OBNSCs was
      characterized by a simultaneous appearance of neurons and glial cells. The
      differentiation medium, containing cAMP, PDGFA, T3, and all-trans-retinoic acid
      (ATRA), promotes OBNSCs to generate mostly oligodendrocytes (OLs) displaying
      morphological changes, and appearance of long cytoplasmic processes. OBNSCs
      showed, after 5 days in OLs differentiation medium, a considerable decrease in
      the number of nestin positive cells, which was associated with a concomitant
      increase of NG2 immunoreactive cells and few O4(+)-OPCs. In addition, a
      significant up regulation in gene and protein expression profile of stage
      specific cell markers for OPCs/OLs (CNPase, Galc, NG2, MOG, OLIG1, OLIG2, MBP),
      neurons, and astrocytes (MAP2, beta-TubulinIII, GFAP) and concomitant decrease of
      OBNSCs pluripotency markers (Oct4, Sox2, Nestin), was demonstrated following
      induction of OBNSCs differentiation. Taken together, the present study
      demonstrate the marked ability of a cocktail of factors containing PDGFA, T3,
      cAMP, and ATRA, to induce OBNSCs differentiation into OPCs/OLs and shed light on
      the key genes and pathological pathways involved in this process.

PMID- 28500735
TI  - Increased expression of CD38 and HLADR in HIV-infected patients with oral lesion.
AB  - Persistent immune actiation is associated with innadequate immune recovery in HIV
      patients. This study assessed the relationship between frequency of expression of
      cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1
      infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral
      treatment, were divided into three groups, according to the number of CD4+ T
      cells and CD4+ /CD8+ ratio: adequate, partial, and inadequate immune
      restauration. All patients underwent full mouth assessments for saliva flow
      measurement, oral mucosal lesion, periodontal disease, and severity of
      periodontitis. Immune activation markers levels were compared according to three
      groups of periodontal disease ("No periodontal disease," "gingivitis," and
      "periodontitis"). Oral mucosal lesions (P = 0.03) and peridodontal disease (P =
      0.03) were associated with lower CD4+ /CD8+ ratio. Patients with oral mucosal
      lesions had significantly higher median levels of HLADR and CD38 markers in all T
      lymphocytes populations than patients without oral lesions. Patients with
      gingivitis and with periodontitis presented significantly higher median levels of
      CD3+ HLADR+ , CD4+ HLADR+ , CD8+ HLADR+ , and CD3+ CD38+ and significantly lower
      CD4+ /CD8+ ratio than patients with no periodontal disease. Increased levels of
      HLADR and CD38 expressions in peripheral blood were associated with oral lesions
      in HIV-positive patients. Periodontal disease was associated with HLADR
      expression.

PMID- 28500736
TI  - High density lipoprotein (HDL) reverses palmitic acid induced energy metabolism
      imbalance by switching CD36 and GLUT4 signaling pathways in cardiomyocyte.
AB  - In our previous study palmitic acid (PA) induced lipotoxicity and switches energy
      metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density
      lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy.
      Therefore, we in the present study investigated whether HDL can reverse PA
      induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2
      cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and
      GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK,
      SIRT1, PGC1alpha, PPARalpha, CPT1beta, and CD36) were decreased by high PA (150
      and 200 MUg/MUl) concentration. Interestingly, expression of GLUT4 metabolic
      pathway proteins (p-PI3K and pAKT) were increased at low concentration (50
      MUg/MUl) and decreased at high PA concentration. Whereas, phospho-PKCzeta, GLUT4
      and PDH proteins expression was increased in a dose dependent manner. PA treated
      H9c2 cells were treated with HDL and analyzed for cell viability. Results showed
      that HDL treatment induced cell proliferation efficiency in PA treated cells. In
      addition, HDL reversed the metabolic effects of PA: CD36 translocation was
      increased and reduced GLUT4 translocation, but HDL treatment significantly
      increased CD36 metabolic pathway proteins and reduced GLUT4 pathway proteins. Rat
      neonatal cardiomyocytes showed similar results. In conclusion, HDL reversed
      palmatic acid-induced lipotoxicity and energy metabolism imbalance in H9c2
      cardiomyoblast cells and in neonatal rat cardiomyocyte cells.

PMID- 28500738
TI  - Occurrence and predictors of acute stent recoil-A comparison between the xience
      prime cobalt chromium stent and the promus premier platinum chromium stent.
AB  - OBJECTIVES: To compare the occurrence of acute stent recoil in two different
      stent types (platinum chromium and cobalt chromium) and identify the potential
      predictors of significant acute stent recoil. BACKGROUND: Acute stent recoil is
      frequently observed after percutaneous coronary intervention and has been
      associated with in-stent restenosis and in-stent thrombosis. Different stent
      designs may result in varying degrees of stent recoil. METHODS: From a registry
      of "all-comers" treated with either the Xience Prime Cobalt Chromium or Promus
      Premier Platinum Chromium stent, a random sample of 100 patients was drawn. Acute
      stent recoil was defined as the minimal luminal diameter (MLD) of the last
      inflated balloon minus the MLD after, divided by the MLD of the last inflated
      balloon. Significant acute stent recoil was defined as recoil >=10%. RESULTS: A
      total of 123 lesions (61 Xience Prime vs 62 Promus Premier) in 100 patients were
      analyzed. Acute stent recoil of 8.6 +/- 4.9% was observed in the Xience Prime
      group versus 8.7 +/- 4.2% in the Promus Premier group, P = 0.970. In a
      multivariate model for significant acute stent recoil, a stent/vessel ratio >=1
      (hazard ratio 4.64 [1.94-11.12], P = 0.001), a balloon/stent ratio >1 (hazard
      ratio 3.83 [1.12-13.14], P = 0.032) and direct stenting (hazard ratio 0.42 [0.18
      0.96], P = 0.039) were identified as predictors. CONCLUSIONS: No significant
      differences were observed in the extent of acute stent recoil between the Xience
      Prime and the Promus Premier stent. A larger stent/vessel ratio, a larger
      balloon/stent ratio, and direct stenting were associated with significant acute
      stent recoil >=10%. (c) 2017 Wiley Periodicals, Inc.

PMID- 28500739
TI  - Feasibility and safety of transfemoral sheathless portico aortic valve
      implantation: Preliminary results in a single center experience.
AB  - BACKGROUND: Feasibility of transfemoral (TF) transcathteter aortic valve
      replacement (TAVR) is limited by the smallest diameter, the calcification and
      tortuosity of the iliofemoral access vessels. The use of the Portico system
      without delivery sheath results in significantly lower profile delivery system
      compared to standard technique. We herein report our single center experience,
      feasibility and safety of such an approach. METHODS: The Portico valve was
      implanted sheathless in 81 high-risk patients with severe aortic stenosis
      utilizing percutaneous femoral access. Mean minimal diameter of the ileo-femoral
      arterial access was 7.06 +/- 1.89 mm. In most cases a multidetector computed
      tomography was performed before the intervention to assess the feasibility of
      vascular access and for aortic annulus measurements. The vascular access site was
      preclosed using two ProGlide suture systems. RESULTS: Device implantation was
      successful 98.7% of patients. Valve recapturing and repositioning as well as
      valve-in-valve deployment was performed in only one case (1.2%). There were no
      infarctions, 2 strokes (2.4%) and 2 acute kidney failure (2.4%), 1 major vascular
      complication1 (1.2%) 4 major bleedings (4.9%), 11 conductions disturbances and
      relative pace-maker implantations (14.2%). The mean gradient decreased from 42.3
      +/- 17 to 6.3 +/- 2.78 mm Hg. Paravalvular regurgitation as assessed by TTE at
      discharge was absent or trivial in 19 patients, mild in 60 and moderate 1. Thirty
      day mortality was 2.4%. CONCLUSIONS: Sheathless use of the Portico valve is
      feasible and appears to be safe, with excellent rates of complications and
      mortality in the short-term. Such an approach has the potential to further expand
      feasibility of TF TAVR to patients with severe peripheral arterial disease.
      Feasibility in patients with smaller femoral access and more challenging anatomy
      has to be proven in further studies. (c) 2017 Wiley Periodicals, Inc.

PMID- 28500737
TI  - Clinical outcomes of overlapping versus non-overlapping everolimus-eluting absorb
      bioresorbable vascular scaffolds: An analysis from the multicentre prospective
      RAI registry (ClinicalTrials.gov identifier: NCT02298413).
AB  - OBJECTIVES: To compare clinical outcomes of patients treated with overlapping
      versus non-overlapping Absorb BVS. BACKGROUND: Limited data are available on the
      clinical impact of stent overlap with the Absorb BVS bioresorbable stent.
      METHODS: We compared outcomes of patients receiving overlapping or non
      overlapping Absorb BVS in the multicenter prospective RAI Registry. RESULTS: Out
      of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for
      this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in
      the non-overlap group. The most frequent overlap configuration was the marker-to
      marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker
      (6%) types. Patients of the overlap group had higher prevalence of multivessel
      disease and higher SYNTAX score, and required more frequently the use of
      intravascular imaging. At a median follow-up of 368 days, no difference was
      observed between overlap and non-overlap groups in terms of a device-related
      composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of
      a patient-related composite endpoint (any death, any MI, any revascularization)
      (15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5%
      vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs.
      1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of
      the overlap population according to overlap configurations used, no difference
      was observed in terms of the device- or patient-related composite endpoints.
      CONCLUSIONS: Outcomes of patients with or without overlapping BVS were comparable
      at mid-term follow-up despite higher angiographic complexity of the overlap
      subset. (c) 2017 Wiley Periodicals, Inc.

PMID- 28500740
TI  - Children with low-risk acute lymphoblastic leukemia are at highest risk of second
      cancers.
AB  - BACKGROUND: The improved survival rates for childhood acute lymphoblastic
      leukemia (ALL) may be jeopardized by the development of a second cancer, which
      has been associated with thiopurine therapy. PROCEDURE: We retrospectively
      analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's
      protocols characterized by increasing intensity of thiopurine-based maintenance
      therapy. We explored the risk of second cancer in relation to protocols, risk
      group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy
      (HeH), and t(12;21)[ETV6/RUNX1]. RESULTS: After median 9.5 years (interquartile
      range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second
      cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard
      risk ALL, who received the longest maintenance therapy, had the highest adjusted
      hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16,
      95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02
      0.49, P = 0.006); no significant effects of protocol, age, or white blood cell
      count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset
      analysis on the patients with standard-risk ALL did not show an increased hazard
      of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69
      5.96, P = 0.20). The effect of low TPMT low activity was explored in patients
      reaching maintenance therapy in clinical remission (n = 3,368); no association
      with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47).
      CONCLUSIONS: The rate of second cancer was generally highest in patients with low
      risk ALL, but we could not identify a subset at higher risk than others.

PMID- 28500741
TI  - Mouth examination performance by children's parents and by adolescents in Fanconi
      anemia.
AB  - BACKGROUND: Fanconi anemia (FA) is a rare genetic syndrome characterized by
      increased risk of developing malignant neoplasms, particularly oral squamous cell
      carcinoma. This study aims to ascertain the extent to which adolescents and
      guardians/parents of children with FA are aware of their oral cancer risks and
      assess their ability to perform mouth examination (ME). PROCEDURE: A cross
      sectional study was conducted among patients with FA (between 6 and 16 years) and
      their parents. A total of 45 patients, 19 children and 26 adolescents,
      participated in the study. Among children less than 12 years of age, caregivers
      performed ME and adolescents between 12 and 16 years of age performed mouth self
      examination (MSE). All parents were given a self-reporting questionnaire to
      collect sociodemographic data, information about health-related behaviors, and
      oral cancer awareness. Performance was evaluated using criteria for mucosal
      visualization and retracting ability. Subsequently, a dentist clinically examined
      all patient participants. RESULTS: Performance evaluation indicated that the
      examination quality was unsatisfactory in both groups. Statistical significance
      was found between ability to perform ME by marital status (P < 0.036), where
      divorced parents had more difficulty performing ME than nondivorced parents.
      CONCLUSION: Oral mucosa surveillance performed by parents and adolescents seems
      to be inaccurate. However, as an oral examination is a relatively inexpensive
      form of secondary prevention, it merits attention to teaching the technique to
      patients with FA and their caregivers.

PMID- 28500742
TI  - Amino acids at positions 3, 168, and 169 are associated with the ability of Nef
      proteins from HIV-1 CRF01_AE to downmodulate CD4.
AB  - Several HIV-1 subtypes are co-circulating among various high-risk groups in
      China, and an increasing prevalence of CRF01_AE was observed among MSM (men who
      have sex with men) within recent years. Patients infected with CRF01_AE may
      experience a more rapid disease progression than patients infected with non
      CRF01_AE; however, the underlying mechanisms remains elusive. HIV-1 Nef is a
      multifunctional protein and plays critical roles in viral pathogenesis. Nef
      downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission
      and escape from the host immune response. In this study, we investigated the CD4
      downmodulation activity of Nef proteins isolated from HIV-1 CRF01_AE and analyzed
      a potential relationship of Nef's capacity to downregulate CD4 with disease
      progression. We found that the majority of these Nefs from HIV-1 CRF01_AE
      efficiently downregulated CD4; Nefs with weaker CD4 downmodulation activity
      tended to be associated with higher CD4 levels and lower viral loads. Further
      elucidation revealed that amino acid residues at positions 3, 168, and 169 of
      CRF01_AE Nefs were associated with the capacity to downregulate CD4. Our data
      suggest that the capacity of Nef-mediated CD4 downregulation is not the only
      determinant for controlling disease progression, and other host and viral factors
      should be considered to explain the rapid disease progression of patients
      infected with HIV-1 CRF01_AE.

PMID- 28500743
TI  - Safety and efficacy of clip-based vs. suture mediated vascular closure for
      femoral access hemostasis: A prospective randomized single center study comparing
      the StarClose and the ProGlide device.
AB  - OBJECTIVES: This study is the first head-to-head analysis of StarClose vs.
      ProGlide in patients undergoing 5F or 6F percutaneous coronary catheterization or
      peripheral artery interventions. BACKGROUND: The clip based StarClose and the
      suture mediated ProGlide vascular closure device are well established for femoral
      hemostasis in endovascular therapy. However, until now no prospective randomized
      study compared the safety and efficacy of the two devices. METHODS: This
      prospective, randomized, single-center study enrolled 505 patients (69.6 +/- 11.2
      years) resulting in 538 procedures due to more than one intervention in several
      patients: We analyzed 422 cardiac catheterization and 116 peripheral artery
      interventions via a common femoral artery access. Patients were randomized to
      StarClose or ProGlide (1:1). In-hospital complications (major bleeding, hematoma,
      pseudoaneurysm, vessel occlusion, and arteriovenous fistula) and device failure
      were recorded. The puncture site was assessed by ultrasound in all patients prior
      to discharge. RESULTS: Overall complication rate was 3.9%. There were more
      complications after utilization of StarClose compared to ProGlide (5.6 vs. 2.2%,
      P = 0.064), which was significant in adjusted logistic regression analysis with a
      2.9-fold increased risk of complications for StarClose (P < 0.05). In the
      subgroup of coronary catheterizations there were significantly more complications
      for StarClose compared to ProGlide (1.4 vs. 5.2%, P < 0.05) with a 4.7-fold
      increased risk. Device failure rate was not significantly different between the
      two devices. CONCLUSION: In this first randomized trial comparing the two closure
      systems complication rate was higher for StarClose with equal efficacy compared
      to ProGlide. (c) 2017 Wiley Periodicals, Inc.

PMID- 28500744
TI  - Risk of cataract among interventional cardiologists and catheterization lab
      staff: A systematic review and meta-analysis.
AB  - OBJECTIVES: We performed a systematic review and meta-analysis to assess the risk
      of developing a radiation-induced cataract in interventional cardiologists (ICs).
      BACKGROUND: ICs are forced to radiation exposure during cardiac catheterization
      procedures. Since the eye lens is one of the most radiosensitive organs in the
      body, ICs are highly susceptible to develop a radiation-induced cataract. METHOD:
      We performed a systematic literature search of nine electronic databases to
      retrieve studies that report cataract among interventional cardiologists. Records
      were screened for eligibility and data were extracted and analyzed using review
      manager (RevMan) for windows. RESULTS: Eight studies involving 2559 subjects
      (exposed ICs = 1224) were included. Posterior lens opacity was significantly
      higher in ICs relative to the control group (RR= 3.21, 95% CI [2.14, 4.83], P <
      0.00001). In contrast, there was no significant difference between both groups in
      cortical lens opacity (RR= 0.69, 95% CI [0.46, 1.06], P = 0.09) and nuclear
      opacity (RR= 0.85, 95% CI [0.71, 1.02], P = 0.08). CONCLUSION: Interventional
      cardiologists are at high risk of developing radiation-induced cataract;
      therefore, protective measures with high safety rates should be implied. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28500745
TI  - Advanced oxidation protein products induce hepatocyte epithelial-mesenchymal
      transition via a ROS-dependent, TGF-beta/Smad signaling pathway.
AB  - Epithelial-mesenchymal transition (EMT) occurs during the progression of liver
      fibrosis in response to chronic liver injury. However, the molecular mechanism
      underlying the regulation of hepatocyte EMT remains unclear. The aim of this
      study was to determine whether advanced oxidation protein products (AOPP) had an
      effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from
      normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro
      and in vivo studies. The expression of cell and molecular markers of EMT in L02
      hepatocytes were studied using Western blotting, and quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) assays. Hepatocyte migratory
      potential was analyzed using a wound healing assay. Intracellular reactive oxygen
      species (ROS) were detected using the dichlorofluorescein (DCF) assay. In liver
      tissue sections, expression of EMT markers was evaluated using
      immunohistochemistry, and collagen was assessed using histochemical staining with
      Masson's trichrome. The findings were that AOPP treatment resulted in EMT in
      hepatocytes, which was associated with reduced expression of E-cadherin,
      increased expression of vimentin, increased deposition of collagen protein, and
      enhanced cell migration in vivo and in vitro. AOPP was also found to promote
      migration in L02 cells, and to promote the production of ROS and the activation
      of TGF-betaR and Smad signaling. Inhibition of the generation of intracellular
      ROS and TGF-beta receptor blocking could reverse AOPP-induced EMT in hepatocytes.
      This study has identified a novel mechanism in the regulation of hepatocyte EMT,
      and the findings may have implications for the control of liver fibrosis.

PMID- 28500746
TI  - Higher viral load and genetic diversity of HIV-1 in seminal compartments than in
      blood of seven Chinese men who have sex with men and have early HIV-1 infection.
AB  - To date, there have been no reports characterizing HIV-1 in the semen of Chinese
      men who have sex with men (MSM) with early infection. In this study, genetic
      diversity and viral load of HIV-1 in the seminal compartments and blood of
      Chinese MSM with early HIV-1 infection were examined. Viral load and genetic
      diversity of HIV-1 in paired samples of semen and blood were analyzed in seven
      MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time
      PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1
      genotype and genetic diversity based on V3 loop amino acid sequences were
      determined by using Geno2pheno and PSSM programs co-receptor usage. It was found
      that there was more HIV-1 RNA in seminal plasma than in blood plasma and total,
      and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in
      peripheral blood mononuclear cells from all seven patients with early HIV
      infection. There was also greater HIV-1 genetic diversity in seminal than in
      blood compartments. HIV-1 in plasma displayed higher genetic diversity than in
      cells from the blood and semen. In addition, V3 loop central motifs, which
      present some key neutralizing antibody epitopes, varied between blood and semen.
      Thus, virological characteristics in semen may be more representative when
      evaluating risk of transmission in persons with early HIV infection.

PMID- 28500747
TI  - Investigating biogeographic boundaries of the Sunda shelf: A phylogenetic
      analysis of two island populations of Macaca fascicularis.
AB  - OBJECTIVES: Cyclical submergence and re-emergence of the Sunda Shelf throughout
      the Pleistocene served as a dynamic biogeographic landscape, across which long
      tailed macaques (Macaca fascicularis) have migrated and evolved. Here, we tested
      the integrity of the previously reported continental-insular haplotype divide
      reported among Y and mitochondrial DNA lineages across multiple studies.
      MATERIALS AND METHODS: The continental-insular haplotype divide was tested by
      heavily sampling wild macaques from two important biogeographic regions within
      Sundaland: (1) Singapore, the southernmost tip of continental Asia and (2) Bali,
      Indonesia, the southeastern edge of the Indonesian archipelago, immediately west
      of Wallace's line. Y DNA was haplotyped for samples from Bali, deep within the
      Indonesian archipelago. Mitochondrial D-loop from both islands was analyzed
      against existing data using Maximum Likelihood and Bayesian approaches. RESULTS:
      We uncovered both "continental" and "insular" Y DNA haplotypes in Bali. Between
      Singapore and Bali we found 52 unique mitochondrial haplotypes, none of which had
      been previously described. Phylogenetic analyses confirmed a major haplogroup
      division within Singapore and identified five new Singapore subclades and two
      primary subclades in Bali. DISCUSSION: While we confirmed the continental-insular
      divide among mtDNA haplotypes, maintenance of both Y DNA haplotypes on Bali, deep
      within the Indonesian archipelago calls into question the mechanism by which Y
      DNA diversity has been maintained. It also suggests the continental-insular
      designation is less appropriate for Y DNA, leading us to propose geographically
      neutral Y haplotype designations.

PMID- 28500748
TI  - Epidemiology and genetic diversity of classic human astrovirus among hospitalized
      children with acute gastroenteritis in Uruguay.
AB  - Classic Human Astrovirus (Classic HAstV) are one of the most important causes of
      pediatric acute gastroenteritis (AGE), after rotaviruses and arguably
      caliciviruses. The aim of this study was to determine the molecular epidemiology
      of Classic HAstV from 175 clinical samples, being 153 stools and 22 vomits,
      collected from pediatric hospitalized patients with AGE in Salto city, Uruguay,
      from January 2011 to December 2012. Classic HAstV were detected and genotyped by
      using a qualitative Retro Transcription-Polimerase Chain Reaction (RT-PCR)
      directed to the Open Reading Frame-2 (ORF2) region C. Amplicons were sequenced
      and phylogenetic analyses were carried out in order to determine genotypes and
      lineages. Classic HAstV were detected in 18 out of 175 analyzed samples (10.3%)
      and 14 of them (78.0%) were successfully sequenced being 6 (42.8%) classified as
      HAstV-1 (1a lineage), 4 (28.6%) as HAstV-2 (2c lineage), and 4 (28.6%) as HAstV-3
      (3c lineage). A higher detection of Classic HAstV infections was observed in
      autumn for both years of surveillance, and the majority of the positive cases
      were observed in 2011. The group of children between 2 and 5 years old presented
      the higher percentage of infections. To our knowledge, the present study
      represents the first report of astrovirus from acute gastroenteritis cases in
      Uruguay, evidencing its role as a relevant etiologic agent in severe cases of
      this disease.

PMID- 28500749
TI  - Local resectability assessment of head and neck cancer: Positron emission
      tomography/MRI versus positron emission tomography/CT.
AB  - BACKGROUND: The purpose of this study was to compare the diagnostic accuracy of
      positron emission tomography (PET)/MRI with PET/CT for local resectability of
      head and neck cancer. METHODS: Sequential contrast-enhanced PET/CT-MRI was
      performed in 58 patients referred for the staging or restaging of head and neck
      cancer. Tumors were assessed with PET/CT and PET/MRI for the presence of
      resectability-defining factors: T4b status (mediastinal invasion, invasion of the
      prevertebral space, and vascular encasement), and another 8 findings that would
      imply obstacles for surgical cure (invasion of the laryngeal cartilage, invasion
      of the preepiglottic fat pad, perineural spread, orbital invasion, bone
      infiltration, skull base invasion, dural infiltration, and invasion of the
      brachial plexus). RESULTS: The sensitivity/specificity/accuracy of local
      resectability-defining factors of PET/CT and PET/MRI was 0.92/0.99/0.98 and
      0.98/0.99/0.99 (P = .727), respectively, per lesion, and 0.96/0.87/0.91 and
      0.96/0.90/0.93 (P = .687), respectively, per patient. CONCLUSION: Both contrast
      enhanced PET/MRI and contrast-enhanced PET/CT can serve as reliable examinations
      for defining local resectability of head and neck cancer.

PMID- 28500750
TI  - Nausea and vomiting in children and adolescents receiving intrathecal
      methotrexate: A prospective, observational study.
AB  - BACKGROUND: The prevalence of nausea and vomiting after receipt of intrathecal
      methotrexate (IT-MTX) in pediatric oncology patients is unknown. METHODS:
      Patients (4-18 years) about to receive IT-MTX were eligible to participate in
      this prospective, observational study. Patients received antiemetics as
      prescribed by their clinical team. Nausea severity (patient-assessed), timing of
      emetic episodes, and administration of antiemetics were recorded beginning
      immediately prior to IT-MTX administration, for the next 24 hr (acute phase), and
      for a maximum of 7 additional days (delayed phase). Complete chemotherapy-induced
      nausea and vomiting (CINV) control was defined as no emetic episodes and no
      nausea. RESULTS: One hundred patients consented to participate in this study; 70
      provided evaluable data (mean age: 8.3 years; range: 4.1-17.6). Most (94%)
      received propofol-containing anesthesia for IT-MTX administration. Most (89%)
      received a 5-HT3 antagonist prior to IT-MTX. During the acute phase, 36 children
      (51%) experienced complete CINV control, 67 (96%) complete vomiting control, and
      36 (51%) complete nausea control. Severe acute phase nausea was reported by 12
      children (17%). During the delayed phase, 35 patients (50%) experienced complete
      CINV control, 60 (86%) complete vomiting control, and 36 (51%) complete nausea
      control. Severe nausea was reported in the delayed phase by 27 (39%) patients.
      CONCLUSIONS: Most pediatric patients who received IT-MTX and prophylaxis with
      ondansetron or granisetron experienced complete acute and delayed vomiting
      control. However, nausea control was poor and severe nausea was reported by many
      children. Effective interventions to control nausea are needed.

PMID- 28500753
TI  - A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients.
AB  - OBJECTIVES: Guidelines recommend a 0-hour/1-hour high-sensitivity cardiac
      troponin T (hs-cTnT) diagnostic strategy in acute chest pain patients. There are,
      however, little data on the performance of this strategy when combined with
      clinical risk stratification. We aimed to evaluate the diagnostic accuracy of an
      accelerated diagnostic protocol (ADP) using the 0-hour/1-hour hs-cTnT strategy
      together with an adapted Thrombolysis In Myocardial Infarction (TIMI) score and
      electrocardiogram (ECG) for ruling out major adverse cardiac events (MACE) within
      30 days. METHODS: This prospective observational study enrolled consecutive
      emergency department (ED) chest pain patients. TIMI score variables, ED
      physicians' assessments of the ECG, and 0- and 1-hour hs-cTnT were collected.
      Thirty-day MACE was defined as acute myocardial infarction (AMI), unstable angina
      (UA), cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac
      arrest, or death of cardiac or unknown cause. RESULTS: A total of 1,020 patients
      were included in the final analysis. The combination of an adapted TIMI score
      <=1, a nonischemic ECG, and either a 0-hour hs-cTnT < 5 ng/L or a 0-hour hs-cTnT
      < 12 ng/L combined with a 1-hour increase < 3 ng/L identified 432 (42.4%)
      patients as very low risk with a negative predictive value of 99.5% (95%
      confidence interval [CI] = 98.3%-99.9%) and a negative likelihood ratio of 0.04
      (95% CI = 0.01-0.14) for 30-day MACE. The ADP missed only two patients with UA
      and no patients with AMI or other forms of MACE. CONCLUSION: An ADP using the
      guideline recommended 0-hour/1-hour hs-cTnT strategy rapidly identified patients
      with a very low risk of 30-day MACE including UA where no further cardiac testing
      would be needed. This could potentially allow safe early discharge of about 40%
      of ED chest pain patients.

PMID- 28500754
TI  - Mutational phospho-mimicry reveals a regulatory role for the XRCC4 and XLF C
      terminal tails in modulating DNA bridging during classical non-homologous end
      joining.
AB  - XRCC4 and DNA Ligase 4 (LIG4) form a tight complex that provides DNA ligase
      activity for classical non-homologous end joining (the predominant DNA double
      strand break repair pathway in higher eukaryotes) and is stimulated by XLF.
      Independently of LIG4, XLF also associates with XRCC4 to form filaments that
      bridge DNA. These XRCC4/XLF complexes rapidly load and connect broken DNA,
      thereby stimulating intermolecular ligation. XRCC4 and XLF both include
      disordered C-terminal tails that are functionally dispensable in isolation but
      are phosphorylated in response to DNA damage by DNA-PK and/or ATM. Here we
      concomitantly modify the tails of XRCC4 and XLF by substituting fourteen
      previously identified phosphorylation sites with either alanine or aspartate
      residues. These phospho-blocking and -mimicking mutations impact both the
      stability and DNA bridging capacity of XRCC4/XLF complexes, but without affecting
      their ability to stimulate LIG4 activity. Implicit in this finding is that
      phosphorylation may regulate DNA bridging by XRCC4/XLF filaments.

PMID- 28500755
TI  - Enhanced FIB-SEM systems for large-volume 3D imaging.
AB  - Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) can automatically
      generate 3D images with superior z-axis resolution, yielding data that needs
      minimal image registration and related post-processing. Obstacles blocking wider
      adoption of FIB-SEM include slow imaging speed and lack of long-term system
      stability, which caps the maximum possible acquisition volume. Here, we present
      techniques that accelerate image acquisition while greatly improving FIB-SEM
      reliability, allowing the system to operate for months and generating
      continuously imaged volumes > 106 um3. These volumes are large enough for
      connectomics, where the excellent z resolution can help in tracing of small
      neuronal processes and accelerate the tedious and time-consuming human
      proofreading effort. Even higher resolution can be achieved on smaller volumes.
      We present example data sets from mammalian neural tissue, Drosophila brain, and
      Chlamydomonas reinhardtii to illustrate the power of this novel high-resolution
      technique to address questions in both connectomics and cell biology.

PMID- 28500757
TI  - Meta-analysis of the effect of the maternal vitamin D level on the risk of
      spontaneous pregnancy loss.
AB  - BACKGROUND: The association between vitamin D deficiency and early spontaneous
      pregnancy loss (SPL) is unclear. OBJECTIVES: To assess the association of serum
      25-hydroxyvitamin D (25(OH)D) and SPL. SEARCH STRATEGY: Embase, PubMed, and Web
      of Science were searched for relevant papers published before February 20, 2016,
      using search terms including "vitamin D" and "pregnancy loss." SELECTION
      CRITERIA: Case-control and cohort studies investigating the relationship of
      maternal serum 25(OH)D and SPL were included. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted original data from the selected papers. The
      DerSimonian-Laird random-effects model was used to perform the meta-analysis.
      Heterogeneity was assessed by calculating I2 . MAIN RESULTS: Five studies,
      including 10 630 pregnant women, met the inclusion criteria. There was no
      significant association between a low 25(OH)D level and an increased risk of SPL.
      In a subgroup analysis, an extremely low 25(OH)D level (<20 ng/mL) was
      significantly associated with an increased risk of SPL in the first trimester
      (relative risk 2.24, 95% confidence interval 1.15-4.37); the heterogeneity across
      studies was not significant (I2 =0.0%, P=0.355). CONCLUSIONS: Severe Vitamin D
      deficiency could be detrimental to early embryonic development and increase the
      risk of early SPL.

PMID- 28500756
TI  - Sphingomyelin metabolism controls the shape and function of the Golgi cisternae.
AB  - The flat Golgi cisterna is a highly conserved feature of eukaryotic cells, but
      how is this morphology achieved and is it related to its function in cargo
      sorting and export? A physical model of cisterna morphology led us to propose
      that sphingomyelin (SM) metabolism at the trans-Golgi membranes in mammalian
      cells essentially controls the structural features of a Golgi cisterna by
      regulating its association to curvature-generating proteins. An experimental test
      of this hypothesis revealed that affecting SM homeostasis converted flat
      cisternae into highly curled membranes with a concomitant dissociation of
      membrane curvature-generating proteins. These data lend support to our hypothesis
      that SM metabolism controls the structural organization of a Golgi cisterna.
      Together with our previously presented role of SM in controlling the location of
      proteins involved in glycosylation and vesicle formation, our data reveal the
      significance of SM metabolism in the structural organization and function of
      Golgi cisternae.

PMID- 28500752
TI  - Which ante mortem clinical features predict progressive supranuclear palsy
      pathology?
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is a neuropathologically defined
      disease presenting with a broad spectrum of clinical phenotypes. OBJECTIVE: To
      identify clinical features and investigations that predict or exclude PSP
      pathology during life, aiming at an optimization of the clinical diagnostic
      criteria for PSP. METHODS: We performed a systematic review of the literature
      published since 1996 to identify clinical features and investigations that may
      predict or exclude PSP pathology. We then extracted standardized data from
      clinical charts of patients with pathologically diagnosed PSP and relevant
      disease controls and calculated the sensitivity, specificity, and positive
      predictive value of key clinical features for PSP in this cohort. RESULTS: Of
      4166 articles identified by the database inquiry, 269 met predefined standards.
      The literature review identified clinical features predictive of PSP, including
      features of the following 4 functional domains: ocular motor dysfunction,
      postural instability, akinesia, and cognitive dysfunction. No biomarker or
      genetic feature was found reliably validated to predict definite PSP. High
      quality original natural history data were available from 206 patients with
      pathologically diagnosed PSP and from 231 pathologically diagnosed disease
      controls (54 corticobasal degeneration, 51 multiple system atrophy with
      predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant
      frontotemporal dementia). We identified clinical features that predicted PSP
      pathology, including phenotypes other than Richardson's syndrome, with varying
      sensitivity and specificity. CONCLUSIONS: Our results highlight the clinical
      variability of PSP and the high prevalence of phenotypes other than Richardson's
      syndrome. The features of variant phenotypes with high specificity and
      sensitivity should serve to optimize clinical diagnosis of PSP. (c) 2017
      International Parkinson and Movement Disorder Society.

PMID- 28500758
TI  - MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and
      scavenging the pro-inflammatory cytokines.
AB  - The MSCs of various origins are known to ameliorate or modulate cell survival
      strategies. We investigated, whether UCB MSCs could improve the survival of the
      human neuronal cells and/or fibroblast assaulted with DPN sera. The results
      showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts
      could effectively scavenge the pro-inflammatory cytokines TNF-alpha, IL-1beta,
      IFN-? and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co
      culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4,
      IL-10 and TGF-beta and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera
      stressed cells. Amelioration of elevated [Ca2+ ]i and cROS, the portent behind
      the NFkappaB/Caspase-3 mediated inflammation in DPN rescued the cells from
      apoptosis. The results of systemic administration of BM MSCs improved DPN
      pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated
      prolonged distal motor latency (control: 0.70 +/- 0.06, DPN: 1.29 +/- 0.13 m/s
      DPN + BM MSCs: 0.89 +/- 0.02 m/s, p < 0.05) and lowered high amplitude of
      compound muscle action potentials (CMAPs) (control: 12.36 +/- 0.41, DPN: 7.52 +/-
      0.61 mV, DPN + MSCs: 8.79 +/- 0.53 mV, p < 0.05), while slowly restoring the
      plasma glucose levels. Together, all these results showed that administration of
      BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine
      signaling and [Ca2+ ]i homeostasis.

PMID- 28500751
TI  - Radiological biomarkers for diagnosis in PSP: Where are we and where do we need
      to be?
AB  - PSP is a pathologically defined neurodegenerative tauopathy with a variety of
      clinical presentations including typical Richardson's syndrome and other variant
      PSP syndromes. A large body of neuroimaging research has been conducted over the
      past two decades, with many studies proposing different structural MRI and
      molecular PET/SPECT biomarkers for PSP. These include measures of brainstem,
      cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging
      abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in
      striatal dopamine imaging and, most recently, PET imaging with ligands that bind
      to tau. Our aim was to critically evaluate the degree to which structural and
      molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP.
      We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original
      research articles published in English over the past 20 years using postmortem
      diagnosis or the NINDS-SPSP criteria as the diagnostic standard from 1996 to
      2016. We define a five-level theoretical construct for the utility of
      neuroimaging biomarkers in PSP, with level 1 representing group-level findings,
      level 2 representing biomarkers with demonstrable individual-level diagnostic
      utility, level 3 representing biomarkers for early disease, level 4 representing
      surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP
      biomarkers of PSP pathology. We discuss the degree to which each of the currently
      available biomarkers fit into this theoretical construct, consider the role of
      biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and
      autopsy confirmed PSP, and emphasize current shortfalls in the field. (c) 2017
      The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of
      International Parkinson and Movement Disorder Society.

PMID- 28500760
TI  - The opposite effects of nitric oxide donor, S-nitrosoglutathione, on myocardial
      ischaemia/reperfusion injury in diabetic and non-diabetic mice.
AB  - Nitric oxide is a potent anti-apoptotic and cardioprotective molecule in healthy
      animals. However, recent study demonstrates that overexpression of eNOS
      exacerbates the liver injury in diabetic animals. whether diabetes may also alter
      NO's biologic activity in ischaemic/reperfused heart remains unknown. The present
      experiment was designed to determine whether the nitric oxide donor, S
      nitrosoglutathione, may exert different effects on diabetic and non-diabetic
      myocardial ischaemia/reperfusion (MI/R) injury. Diabetic state was induced in
      mice by multiple intraperitoneal injections of low-dose streptozotocin (STZ). The
      control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours
      reperfusion. At 10 minutes before reperfusion, diabetic and non-diabetic mice
      were received an intraperitoneal injection of S-nitrosoglutathione (GSNO, a
      nitric oxide donor, 1 MUmol/kg). GSNO attenuated MI/R injury in non-diabetic
      mice, as measured by improved cardiac function, reduced infarct size and
      decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but,
      rather, aggravated the MI/R injury in diabetic mice. Mechanically, the diabetic
      heart exhibited an increased nitrative/oxidative stress level, as measured by
      peroxynitrite formation, compared with non-diabetic mice. Co-administration of
      GSNO with EUK134 (a peroxynitrite scavenger) or MnTE-2-PyP5 (a superoxide
      dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before
      reperfusion significantly decreased the MI/R-induced peroxynitrite formation and
      the MI/R injury. Collectively, the present study for the first time demonstrated
      that diabetes may cause superoxide overproduction, increase NO inactivation and
      peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule
      to a cardiotoxic molecule.

PMID- 28500759
TI  - A Monte Carlo model for mean glandular dose evaluation in spot compression
      mammography.
AB  - PURPOSE: To characterize the dependence of normalized glandular dose (DgN) on
      various breast model and image acquisition parameters during spot compression
      mammography and other partial breast irradiation conditions, and evaluate
      alternative previously proposed dose-related metrics for this breast imaging
      modality. METHODS: Using Monte Carlo simulations with both simple homogeneous
      breast models and patient-specific breasts, three different dose-related metrics
      for spot compression mammography were compared: the standard DgN, the normalized
      glandular dose to only the directly irradiated portion of the breast (DgNv), and
      the DgN obtained by the product of the DgN for full field irradiation and the
      ratio of the mid-height area of the irradiated breast to the entire breast area
      (DgNM ). How these metrics vary with field-of-view size, spot area thickness, x
      ray energy, spot area and position, breast shape and size, and system geometry
      was characterized for the simple breast model and a comparison of the simple
      model results to those with patient-specific breasts was also performed. RESULTS:
      The DgN in spot compression mammography can vary considerably with breast area.
      However, the difference in breast thickness between the spot compressed area and
      the uncompressed area does not introduce a variation in DgN. As long as the spot
      compressed area is completely within the breast area and only the compressed
      breast portion is directly irradiated, its position and size does not introduce a
      variation in DgN for the homogeneous breast model. As expected, DgN is lower than
      DgNv for all partial breast irradiation areas, especially when considering spot
      compression areas within the clinically used range. DgNM underestimates DgN by
      6.7% for a W/Rh spectrum at 28 kVp and for a 9 * 9 cm2 compression paddle.
      CONCLUSION: As part of the development of a new breast dosimetry model, a task
      undertaken by the American Association of Physicists in Medicine and the European
      Federation of Organizations of Medical Physics, these results provide insight on
      how DgN and two alternative dose metrics behave with various image acquisition
      and model parameters.

PMID- 28500761
TI  - Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3
      dependent regulation of oxidative stress and apoptosis.
AB  - Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine
      nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the
      sirtuin family that is localized primarily to the mitochondria and protects
      against oxidative stress-related diseases, including myocardial
      ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in
      ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R
      injury by activating the SIRT3 signaling pathway. In this study, mice were
      pretreated with or without a selective SIRT3 inhibitor and then subjected to MI/R
      operation. Melatonin was administered intraperitoneally (20 mg/kg) 10 minutes
      before reperfusion. Melatonin treatment improved postischemic cardiac contractile
      function, decreased infarct size, diminished lactate dehydrogenase release,
      reduced the apoptotic index, and ameliorated oxidative damage. Notably, MI/R
      induced a significant decrease in myocardial SIRT3 expression and activity,
      whereas the melatonin treatment upregulated SIRT3 expression and activity, and
      thus decreased the acetylation of superoxide dismutase 2 (SOD2). In addition,
      melatonin increased Bcl-2 expression and decreased Bax, Caspase-3, and cleaved
      Caspase-3 levels in response to MI/R. However, the cardioprotective effects of
      melatonin were largely abolished by the selective SIRT3 inhibitor 3-(1H-1,2,3
      triazol-4-yl)pyridine (3-TYP), suggesting that SIRT3 plays an essential role in
      mediating the cardioprotective effects of melatonin. In vitro studies confirmed
      that melatonin also protected H9c2 cells against simulated ischemia/reperfusion
      injury (SIR) by attenuating oxidative stress and apoptosis, while SIRT3-targeted
      siRNA diminished these effects. Taken together, our results demonstrate for the
      first time that melatonin treatment ameliorates MI/R injury by reducing oxidative
      stress and apoptosis via activating the SIRT3 signaling pathway.

PMID- 28500762
TI  - Methyl aminolevulinate photodynamic therapy combined with curettage debulking for
      pigmented basal cell carcinoma.

PMID- 28500763
TI  - Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell
      Immunity in the Global Burden of Atherosclerosis.
AB  - Changes in immune and inflammatory responses may play a crucial role in the
      development and progression of atherosclerosis, as an autoimmune, chronic and
      progressive inflammatory disease. Immunological activity and vascular
      inflammation during atherosclerosis can be modulated by autoimmune responses
      against self-antigens, according to changeable risk factors (cholesterol,
      oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids,
      etc.), and accompanied by accumulation of leucocytes and proinflammatory
      cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs),
      whose concentration are increased in foam cell-rich regions. Regulatory T cells
      (Tregs) represent a unique subpopulation of T cells specialized in the regulation
      of immune response and in the suppression of proatherogenic T cells. The aim of
      our study was to examine the interactions between the concentration of enzyme
      matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of
      Tregs in peripheral blood of two groups of patients: with carotid artery stenosis
      (CAS), undergoing surgery and with mild atherosclerosis (A) from general
      practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme
      MMP expression, and Tregs was examined by flow cytometric analysis. Our data have
      showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A
      patients in comparison with healthy controls and indicated this method as an easy
      marker for the monitoring of the development of atherosclerosis. Simultaneously,
      the diminished number of Tregs in the same patients pointed the importance of
      these regulatory mechanisms in the etiopathogenesis of atherosclerosis and
      possible Tregs-mediated therapy.

PMID- 28500765
TI  - Developing Bayesian networks from a dependency-layered ontology: A proof-of
      concept in radiation oncology.
AB  - PURPOSE: Bayesian networks (BNs) are graphical representations of probabilistic
      knowledge that offer normative reasoning under uncertainty and are well suited
      for use in medical domains. Traditional knowledge-based network development of BN
      topology requires that modeling experts establish relevant dependency links
      between domain concepts by searching and translating published literature,
      querying domain experts, or applying machine learning algorithms on data. For
      initial development these methods are time-intensive and this cost hinders the
      growth of BN applications in medical decision making. Further, this approach
      fails to utilize knowledge representation in medical fields to automate network
      development. Our research alleviates the challenges surrounding BN modeling in
      radiation oncology by leveraging an ontology based hub and spoke system for BN
      construction. METHODS: We implement a hub and spoke system by developing (a) an
      ontology of knowledge in radiation oncology (the hub) which includes dependency
      semantics similar to BN relations and (b) a software tool that operates on
      ontological semantics using deductive reasoning to create BN topologies (the
      spokes). We demonstrate that network topologies built using the software are
      terminologically consistent and form networks that are topologically compatible
      with existing ones. We do this first by merging two different BN models for
      prostate cancer radiotherapy prediction which contain domain cross terms. We then
      use the logic to perform discovery of new causal chains between radiation
      oncology concepts. RESULTS: From the radiation oncology (RO) ontology we
      successfully reconstructed a previously published prostate cancer radiotherapy
      Bayes net using up-to-date domain knowledge. Merging this model with another
      similar prostate cancer model in the RO domain produced a larger, highly
      interconnected model representing the expanded scope of knowledge available
      regarding prostate cancer therapy parameters, complications, and outcomes. The
      causal discovery resulted in an automatically-built causal network model of all
      ontologized radiotherapy concepts between a 'Mucositis' complication and anatomic
      tumor location. CONCLUSIONS: The proposed model building approach lowers barriers
      to developing probabilistic models relevant to real-world clinical decision
      making, and offers a solution to the consistency and compatibility problems.
      Further, the knowledge representation in this work demonstrates potential for
      broader radiation oncology applications outside of Bayes nets.

PMID- 28500764
TI  - Phylogeny is a powerful tool for predicting plant biomass responses to nitrogen
      enrichment.
AB  - Increasing rates of anthropogenic nitrogen (N) enrichment to soils often lead to
      the dominance of nitrophilic plant species and reduce plant diversity in natural
      ecosystems. Yet, we lack a framework to predict which species will be winners or
      losers in soil N enrichment scenarios, a framework that current literature
      suggests should integrate plant phylogeny, functional tradeoffs, and nutrient co
      limitation. Using a controlled fertilization experiment, we quantified biomass
      responses to N enrichment for 23 forest tree species within the genus Eucalyptus
      that are native to Tasmania, Australia. Based on previous work with these
      species' responses to global change factors and theory on the evolution of plant
      resource-use strategies, we hypothesized that (1) growth responses to N
      enrichment are phylogenetically structured, (2) species with more resource
      acquisitive functional traits have greater growth responses to N enrichment, and
      (3) phosphorus (P) limits growth responses to N enrichment differentially across
      species, wherein P enrichment increases growth responses to N enrichment more in
      some species than others. We built a hierarchical Bayesian model estimating
      effects of functional traits (specific leaf area, specific stem density, and
      specific root length) and P fertilization on species' biomass responses to N,
      which we then compared between lineages to determine whether phylogeny explains
      variation in responses to N. In concordance with literature on N limitation, a
      majority of species responded strongly and positively to N enrichment. Mean
      responses ranged three-fold, from 6.21 (E. pulchella) to 16.87 (E. delegatensis)
      percent increases in biomass per g N.m-2 .yr-1 added. We identified a strong
      difference in responses to N between two phylogenetic lineages in the Eucalyptus
      subgenus Symphyomyrtus, suggesting that shared ancestry explains variation in N
      limitation. However, our model indicated that after controlling for phylogenetic
      non-independence, eucalypt responses to N were not associated with functional
      traits (although post-hoc analyses show a phylogenetic pattern in specific root
      length similar to that of responses to N), nor were responses differentially
      limited by P. Overall, our model results suggest that phylogeny is a powerful
      predictor of winners and losers in anthropogenic N enrichment scenarios in
      Tasmanian eucalypts, which may have implications for other species.

PMID- 28500767
TI  - Metformin for high-altitude performance?
AB  - Metformin has been introduced for treatment of type 2 diabetes but may also have
      ergogenic properties at high altitude by improving muscle glycogen repletion.
      However, very little information is available on potential risks associated with
      the (mis)use of metformin by healthy people.

PMID- 28500766
TI  - Melatonin inhibits neuronal dysfunction-associated with neuroinflammation by
      atopic psychological stress in NC/Nga atopic-like mouse models.
AB  - Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin
      disease. AD can increase psychological stress as well, increasing glucocorticoid
      release and exacerbating the associated symptoms. Chronic glucocorticoid
      elevation disturbs neuroendocrine signaling and can induce neuroinflammation,
      neurotoxicity, and cognitive impairment; however, it is unclear whether AD
      related psychological stress elevates glucocorticoids enough to cause neuronal
      damage. Therefore, we assessed the effects of AD-induced stress in a mouse AD
      model. AD-related psychological stress increased astroglial and microglial
      activation, neuroinflammatory cytokine expression, and markers of neuronal loss.
      Notably, melatonin administration inhibited the development of skin lesions,
      scratching behavior, and serum IgE levels in the model mice, and additionally
      caused a significant reduction in corticotropin-releasing hormone responsiveness,
      and a significant reduction in neuronal damage. Finally, we produced similar
      results in a corticosterone-induced AD-like skin model. This is the first study
      to demonstrate that AD-related psychological stress increases neuroendocrine
      dysfunction, exacerbates neuroinflammation, and potentially accelerates other
      neurodegenerative disease states.

PMID- 28500768
TI  - Can constitutive pigmentation be measured on upper inner arm? Correlation between
      arm and buttocks pigmentation.

PMID- 28500769
TI  - Biogeochemistry drives diversity in the prokaryotes, fungi, and invertebrates of
      a Panama forest.
AB  - Humans are both fertilizing the world and depleting its soils, decreasing the
      diversity of aquatic ecosystems and terrestrial plants in the process. We know
      less about how nutrients shape the abundance and diversity of the prokaryotes,
      fungi, and invertebrates of Earth's soils. Here we explore this question in the
      soils of a Panama forest subject to a 13-yr fertilization with factorial
      combinations of nitrogen (N), phosphorus (P), and potassium (K) and a separate
      micronutrient cocktail. We contrast three hypotheses linking biogeochemistry to
      abundance and diversity. Consistent with the Stress Hypothesis, adding N
      suppressed the abundance of invertebrates and the richness of all three groups of
      organisms by ca. 1 SD or more below controls. Nitrogen addition plots were 0.8 pH
      units more acidic with 18% more exchangeable aluminum, which is toxic to both
      prokaryotes and eukaryotes. These stress effects were frequently reversed,
      however, when N was added with P (for prokaryotes and invertebrates) and with
      added K (for fungi). Consistent with the Abundance Hypothesis, adding P generally
      increased prokaryote and invertebrate diversity, and adding K enhanced
      invertebrate diversity. Also consistent with the Abundance Hypothesis, increases
      in invertebrate abundance generated increases in richness. We found little
      evidence for the Competition Hypothesis: that single nutrients suppressed
      diversity by favoring a subset of high nutrient specialists, and that nutrient
      combinations suppressed diversity even more. Instead, combinations of nutrients,
      and especially the cation/micronutrient treatment, yielded the largest increases
      in richness in the two eukaryote groups. In sum, changes in soil biogeochemistry
      revealed a diversity of responses among the three dominant soil groups, positive
      synergies among nutrients, and-in contrast with terrestrial plants-the frequent
      enhancement of soil biodiversity.

PMID- 28500770
TI  - The role of melatonin in the neurodevelopmental etiology of schizophrenia: A
      study in human olfactory neuronal precursors.
AB  - Dim light exposure of the mother during pregnancy has been proposed as one of the
      environmental factors that affect the fetal brain development in schizophrenia.
      Melatonin circulating levels are regulated by the environmental light/dark cycle.
      This hormone stimulates neuronal differentiation in the adult brain. However,
      little is known about its role in the fetal human brain development. Olfactory
      neuronal precursors (ONPs) are useful for studying the physiopathology of
      neuropsychiatric diseases because they mimic all the stages of neurodevelopment
      in culture. Here, we first characterized whether melatonin stimulates neuronal
      differentiation in cloned ONPs obtained from a healthy control subject (HCS).
      Then, melatonin effects were evaluated in primary cultures of ONPs derived from a
      patient diagnosed with schizophrenia (SZ) and an age- and gender-matched HCS.
      Axonal formation was evidenced morphologically by tau immunostaining and by
      GSK3beta phosphorylated state. Potassium-evoked secretion was assessed as a
      functional feature of differentiated neurons. As well, we report the expression
      of MT1/2 receptors in human ONPs for the first time. Melatonin stimulated axonal
      formation and ramification in cloned ONPs through a receptor-mediated mechanism
      and enhanced the amount and velocity of axonal and somatic secretion. SZ ONPs
      displayed reduced axogenesis associated with lower levels of pGSK3beta and less
      expression of melatonergic receptors regarding the HCS ONPs. Melatonin
      counteracted this reduction in SZ cells. Altogether, our results show that
      melatonin signaling is crucial for functional differentiation of human ONPs,
      strongly suggesting that a deficit of this indoleamine may lead to an impaired
      neurodevelopment which has been associated with the etiology of schizophrenia.

PMID- 28500771
TI  - Large animal models of traumatic brain injury.
AB  - Animal models are essential to gain a deeper understanding of the pathophysiology
      associated with traumatic brain injury (TBI). Rodent models of TBI have proven
      highly valuable with respect to the information they have provided over the
      years, particularly when it comes to the molecular understanding of injury
      mechanisms. However, there has been a failure to translate the successes in
      therapeutic treatment of TBI in rodents, which many believe may be related to
      their different brain anatomy compared with humans. Specifically, the rodent
      lissencephalic brain within its bony skull responds differently to injury than a
      human gyrencephalic brain, particularly from a biomechanical and physiological
      perspective. There is now far greater interest in developing more clinically
      relevant, large animal models of TBI so as to enhance the possibility of
      successful clinical translation. The current mini-review highlights the
      differences between lissencephalic and gyrencephalic brains, emphasizing how
      these differences might impact studies of TBI. Thereafter follows a summary of
      the different large animal models, with a critical analysis of their strengths
      and weaknesses.

PMID- 28500772
TI  - A test of genomic modularity among life-history adaptations promoting speciation
      with gene flow.
AB  - Speciation with gene flow may require adaptive divergence of multiple traits to
      generate strong ecologically based reproductive isolation. Extensive negative
      pleiotropy or physical linkage of genes in the wrong phase affecting these
      diverging traits may therefore hinder speciation, while genetic independence or
      "modularity" among phenotypic traits may reduce constraints and facilitate
      divergence. Here, we test whether the genetics underlying two components of
      diapause life history, initial diapause intensity and diapause termination
      timing, constrain differentiation between sympatric hawthorn and apple-infesting
      host races of the fly Rhagoletis pomonella through analysis of 10,256 SNPs
      measured via genotyping-by-sequencing (GBS). Loci genetically associated with
      diapause termination timing were mainly observed for SNPs mapping to chromosomes
      1-3 in the genome, most notably for SNPs displaying higher levels of linkage
      disequilibrium (LD), likely due to inversions. In contrast, selection on initial
      diapause intensity affected loci on all five major chromosomes of the genome,
      specifically those showing low levels of LD. This lack of overlap in genetically
      associated loci suggests that the two diapause phenotypes are largely modular. On
      chromosome 2, however, intermediate level LD loci and a subgroup of high LD loci
      displayed significant negative relationships between initial diapause intensity
      and diapause termination time. These gene regions on chromosome 2 therefore
      affected both traits, while most regions were largely independent. Moreover, loci
      associated with both measured traits also tended to exhibit highly divergent
      allele frequencies between the host races. Thus, the presence of nonoverlapping
      genetic modules likely facilitates simultaneous, adaptive divergence for the
      measured life-history components.

PMID- 28500773
TI  - The energy sensing LKB1-AMPKalpha1 pathway regulates IGF1 secretion and
      consequent activation of the IGF1R-PKB pathway in primary hepatocytes.
AB  - The insulin-like growth factor 1 (IGF1) pathway has been linked with various
      diseases including diabetes, cancer and aging. In contrast to the well
      established regulatory mechanisms controlling IGF1 expression, molecular
      mechanisms regulating its secretion are not fully understood. The AMP-activated
      protein kinase (AMPK) is a key energy sensor, and cumulative evidence shows that
      it is an attractive therapeutic target for treatment of diabetes, cancer and
      aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse
      primary hepatocytes. Furthermore, we found that AMPKalpha1 but not AMPKalpha2 was
      involved in regulation of IGF1 secretion in mouse primary hepatocytes. Knockout
      of AMPK caused activation of the IGF1 receptor (IGF1R)-protein kinase B (PKB;
      also known as Akt) pathway in hepatocytes, which was mediated by hypersecretion
      of IGF1. Upstream of AMPK, liver kinase B1 (LKB1) was responsible for AMPK
      dependent suppression of IGF1 secretion in hepatocytes. Collectively, these
      findings demonstrate that the energy-sensing LKB1-AMPK pathway regulates IGF1
      secretion in mouse primary hepatocytes, which in turn regulates activation of the
      IGF1R-PKB pathway.

PMID- 28500774
TI  - The transcriptional landscape of seasonal coat colour moult in the snowshoe hare.
AB  - Seasonal coat colour change is an important adaptation to seasonally changing
      environments but the evolution of this and other circannual traits remains poorly
      understood. In this study, we use gene expression to understand seasonal coat
      colour moulting in wild snowshoe hares (Lepus americanus). We used hair colour to
      follow the progression of the moult, simultaneously sampling skin from three
      moulting stages in hares collected during the peak of the spring moult from white
      winter to brown summer pelage. Using RNA sequencing, we tested whether patterns
      of expression were consistent with predictions based on the established phases of
      the hair growth cycle. We found functionally consistent clustering across skin
      types, with 766 genes differentially expressed between moult stages. "White"
      pelage showed more differentially expressed genes that were upregulated relative
      to other skin types, involved in the transition between late telogen (quiescent
      stage) and the onset of anagen (proliferative stage). Skin samples from
      transitional "intermediate" and "brown" pelage were transcriptionally similar and
      resembled the regressive transition to catagen (regressive stage). We also
      detected differential expression of several key circadian clock and pigmentation
      genes, providing important means to dissect the bases of alternate seasonal
      colour morphs. Our results reveal that pelage colour is a useful biomarker for
      seasonal change but that there is a consistent lag between the main gene
      expression waves and change in visible coat colour. These experiments establish
      that developmental sampling from natural populations of nonmodel organisms can
      provide a crucial resource to dissect the genetic basis and evolution of complex
      seasonally changing traits.

PMID- 28500775
TI  - Vaccines against malaria-still a long way to go.
AB  - Several species of Plasmodium cause a broad spectrum of human disease that range
      from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure.
      In malaria-endemic countries, continuous exposure to Plasmodium sporozoite
      inoculations and subsequent blood infections elicit only partial and short-lived
      immunity, which gradually develops over many years of parasite exposure and
      multiple clinical episodes. The ambitious goal of malaria vaccinology over the
      past 70 years has been to develop an immunization strategy that mounts protection
      superior to naturally acquired immunity. Herein, three principal concepts in
      evidence-based malaria vaccine development are compared. Feasible leads are
      typically stand-alone subunit vaccine approaches that block Plasmodium parasite
      life cycle progression or parasite/host interactions, and they constitute the
      majority of candidates in preclinical research and early clinical testing.
      Integrated approaches incorporate malaria antigen(s) into licensed or emerging
      pediatric vaccine formulations. This strategy can complement the malaria control
      portfolio even if the antimalarial component is only partially effective and has
      led to the development of the only candidate vaccine to date, namely RTS,S-AS01.
      Experimental whole parasite vaccine approaches have been repeatedly shown to
      elicit sterile and lasting protection against identical parasite strains, but
      mass production, proof of broad protection against different parasite strains,
      and routes of vaccine delivery remain significant translational road blocks.
      Global access to an effective and affordable malaria vaccine will critically
      depend on innovative translational research that builds on a better molecular
      understanding of Plasmodium biology and host immunity.

PMID- 28500776
TI  - Analysis of National Pharmacovigilance Data Associated with Statin Use in Korea.
AB  - The aim of this study was to evaluate clinical manifestations, age distribution
      and risk factors of adverse drug reactions (ADRs) of statins. Korean Adverse
      Event Reporting System (KAERS) database records (July 2009-June 2014) on statin
      treated adults were used. ADRs classified as 'certain', 'probable' and 'possible'
      based on the WHO-Uppsala Monitoring Centre criteria were analysed. The frequency
      of ADRs was compared between adults (18-64 years) and older people (age >=65
      years) groups. In total, 2161 ADRs from 1690 patients (579, 34.3% older people)
      were included for analysis. Mean patient age and ADRs per patient were 60.46 +/-
      12.72 years and 1.28, respectively. ADRs were reported with atorvastatin (48.4%),
      rosuvastatin (23.0%), pitavastatin (10.4%) and simvastatin (9.1%). The frequent
      ADRs were gastrointestinal (421 events, 19.5%), musculoskeletal (331, 15.3%),
      skin (312, 14.4%) and hepatobiliary disorders (286, 13.2%). Skin disorders were
      significantly more frequent in adults compared to those in older patients (16.3%
      versus 12.4%, p = 0.021). Common clinical symptoms were myalgia (263 events,
      12.2%), dyspepsia (133, 6.2%) and pruritus (103, 4.8%). Myalgia was more
      frequently reported in adults (12.7% versus 9.5%, p = 0.039) and dizziness was
      more frequent in older people (3.4% versus 5.8%, p = 0.015). According to KAERS
      data, leading statin ADRs were gastrointestinal and musculoskeletal disorders.
      Myalgia and dyspepsia were the common clinical symptoms.

PMID- 28500777
TI  - A comprehensive investigation of starch degradation process and identification of
      a transcriptional activator MabHLH6 during banana fruit ripening.
AB  - Although starch degradation has been well studied in model systems such as
      Arabidopsis leaves and cereal seeds, this process in starchy fruits during
      ripening, especially in bananas, is largely unknown. In this study, 38 genes
      encoding starch degradation-related proteins were identified and characterized
      from banana fruit. Expression analysis revealed that 27 candidate genes were
      significantly induced during banana fruit ripening, with concomitant conversion
      of starch-to-sugars. Furthermore, iTRAQ-based proteomics experiments identified
      18 starch degradation-associated enzymes bound to the surface of starch granules,
      of which 10 were markedly up-regulated during ripening. More importantly, a novel
      bHLH transcription factor, MabHLH6, was identified based on a yeast one-hybrid
      screening using MaGWD1 promoter as a bait. Transcript and protein levels of
      MabHLH6 were also increased during fruit ripening. Electrophoretic mobility shift
      assays, chromatin immunoprecipitation and transient expression experiments
      confirmed that MabHLH6 activates the promoters of 11 starch degradation-related
      genes, including MaGWD1, MaLSF2, MaBAM1, MaBAM2, MaBAM8, MaBAM10, MaAMY3,
      MaAMY3C, MaISA2, MaISA3 and MapGlcT2-2 by recognizing their E-box (CANNTG) motifs
      present in the promoters. Collectively, these findings suggest that starch
      degradation during banana fruit ripening may be attributed to the complex actions
      of numerous enzymes related to starch breakdown at transcriptional and
      translational levels, and that MabHLH6 may act as a positive regulator of this
      process via direct activation of a series of starch degradation-related genes.

PMID- 28500778
TI  - Phaeohyphomycosis due to Exophiala infections in solid organ transplant
      recipients: Case report and literature review.
AB  - This case report and literature review underscores the cutaneous presentations of
      phaeohyphomycosis in the solid organ transplant population. Increased cognizance
      with prompt identification is critical. The therapy and clinical outcomes of
      phaeohyphomycosis, caused by the Exophiala genus, in the solid organ transplant
      population, is analyzed to examine optimal care. This review highlights the
      inherent difficulties in providing the appropriate duration of antifungal therapy
      to avoid relapsing infections in immunosuppressed patients.

PMID- 28500779
TI  - Beyond nutrients: a meta-analysis of the diverse effects of arbuscular
      mycorrhizal fungi on plants and soils.
AB  - Arbuscular mycorrhizal fungi (AMF) can increase plant fitness under certain
      environmental conditions. Among the mechanisms that may drive this mutualism, the
      most studied is provisioning of nutrients by AMF in exchange for carbon from
      plant hosts. However, AMF may also provide a suite of non-nutritional benefits to
      plants including improved water uptake, disease resistance, plant chemical
      defense, soil aggregation, and allelochemical transport and protection. Here, we
      use a meta-analysis of 93 studies to assess the relative effect of AMF on
      nutritional and non-nutritional factors that may influence plant fitness. We find
      that the positive effects of AMF on soil aggregation, water flow and disease
      resistance are equal to the effect of AMF on plant nitrogen and phosphorus
      uptake. However, AMF had no effect on the uptake of other nutrients, plant water
      content, allelopathic transport or production of chemical defense compounds. We
      suggest future research directions, including experimentally assessing the
      relative contribution on plant fitness of AMF interactions by untangling the
      independence of alternative benefits of AMF from an increase in nutrient uptake.
      This will lead to a more holistic view of the mycorrhizal-plant association and a
      more accurate picture of the net impact on the plant or plant community in
      question.

PMID- 28500780
TI  - Prognostic factors of maternal near miss events and maternal deaths in a tertiary
      healthcare facility in India.
AB  - OBJECTIVE: To study maternal near miss (MNM) and maternal mortality to identify
      rectifiable risk factors. METHODS: The present cross-sectional retrospective
      study included pregnant women who experienced acute life-threatening pregnancy
      related adverse events at Deen Dayal Upadhyay hospital, New Delhi, India, between
      September 1, 2009, and August 31, 2011. Patient data were analyzed to investigate
      factors associated with MNM events and maternal deaths. RESULTS: There were 369
      patients included, and 302 MNM events and 67 maternal deaths were recorded. The
      recorded causes of MNM events included hemorrhage, hypertensive disorders, severe
      anemia with cardiac failure, organ failure, and infection in 192 (63.6%), 62
      (20.5%), 13 (4.3%), 8 (2.6%), and 8 (2.6%) patients, respectively. Higher rates
      of anemia (P=0.007) and infection (P=0.007) were recorded among patients in the
      maternal death group than the MNMN group. CONCLUSION: Hemorrhage and hypertension
      were major causes of MNM events and are likely major barriers to reducing
      maternal mortality in low-income countries. Anemia and infection were significant
      prognostic factors of maternal death in the present study. MNM could be used as
      surrogate for maternal death in the provision of standard obstetric care.

PMID- 28500781
TI  - Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a
      national French survey study.
AB  - Simultaneous pancreas and kidney transplantation (SPK) is currently the best
      therapeutic option for patients with type 1 diabetes and terminal renal failure.
      Renal transplantation restores fertility enabling women to pursue pregnancies.
      However, scarcity of available data on pregnancy outcomes in SPK impedes fair
      medical counseling. Medical files of all pregnancies that lasted >=3 months among
      recipients of functional SPK performed between 1990 and 2015 in France were
      retrospectively analyzed. Twenty-six pregnancies in 22 SPK recipients were
      identified. Main maternal complications included gestational hypertension (53.8%)
      and infections (50%). Cesarean section was performed in 73% of cases. Overall
      fetal survival was 92.6% with a mean gestational age of 34.2 +/- 3 weeks. Four
      children (16.7% of live births) had a birth weight <10th percentile. Endocrine
      pancreas graft function remained stable during pregnancy. An acute kidney
      rejection occurred in two patients, one of which resulting in graft loss. Kidney
      and pancreas graft survival was, respectively, 96% and 100% at 1 year
      postconception and did not differ from controls. Pregnancy in SPK is feasible,
      but patients should be informed of the risks for the fetus, the mother, and the
      grafts. Planning of pregnancy in SPK women is key to allow a personalized
      multidisciplinary monitoring, which represents the most straightforward approach
      to optimize outcomes.

PMID- 28500783
TI  - On mixed electron-photon radiation therapy optimization using the column
      generation approach.
AB  - PURPOSE: Despite considerable increase in the number of degrees of freedom
      handled by recent radiotherapy optimisation algorithms, treatments are still
      typically delivered using a single modality. Column generation is an iterative
      method for solving large optimisation problems. It is well suited for mixed
      modality (e.g., photon-electron) optimisation as the aperture shaping and
      modality selection problem can be solved rapidly, and the performance of the
      algorithm scales favourably with increasing degrees of freedom. We demonstrate
      that the column generation method applied to mixed photon-electron planning can
      efficiently generate treatment plans and investigate its behaviour under
      different aperture addition schemes. MATERIALS AND METHODS: Column generation was
      applied to the problem of mixed-modality treatment planning for a chest wall case
      and a leg sarcoma case. 6 MV beamlets (100 cm SAD) were generated for the photon
      components along with 5 energies for electron beamlets (6, 9, 12, 16 and 20 MeV),
      simulated as shortened-SAD (80 cm) beams collimated with a photon MLC. For the
      chest wall case, IMRT-only, modulated electron radiation therapy (MERT)-only, and
      mixed electron-photon (MBRT) treatment plans were created using the same planning
      criteria. For the sarcoma case, MBRT and MERT plans were created to study the
      behaviour of the algorithm under two different sets of planning criteria designed
      to favour specific modalities. Finally, the efficiency and plan quality of four
      different aperture addition schemes was analysed by creating chest wall MBRT
      treatment plans which incorporate more than a single aperture per iteration of
      the column generation loop based on a heuristic aperture ranking scheme. RESULTS:
      MBRT plans produced superior target coverage and homogeneity relative to IMRT and
      MERT plans created using the same optimisation criteria, all the while preserving
      the normal tissue-sparing advantages of electron therapy. Adjusting the planning
      criteria to favour a specific modality in the sarcoma case resulted in the
      algorithm correctly emphasizing the appropriate modality. As expected, adding a
      single aperture per iteration yielded the lowest (best) cost function value per
      aperture included in the treatment plan. However, a greedier scheme was able to
      converge to approximately the same cost function after 125 apertures in one third
      of the running time. Electron apertures were on average 50-100% larger than
      photon apertures for all aperture addition schemes. The distribution of
      intensities among the available modalities followed a similar trend for all
      schemes, with the dominant modalities being 6 MV photons along with 6, 9 and 20
      MeV electrons. CONCLUSION: The column generation method applied to mixed modality
      treatment planning was able to produce clinically realistic treatment plans and
      combined the advantages of photon and electron radiotherapy. The running time of
      the algorithm depended heavily on the choice of mixing scheme. Adding the highest
      ranked aperture for each modality provided the best trade-off between running
      time and plan quality for a fixed number of apertures. This work contributes an
      efficient methodology for the planning of mixed electron-photon treatments.

PMID- 28500782
TI  - Melatonin protects bone marrow mesenchymal stem cells against iron overload
      induced aberrant differentiation and senescence.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem
      cells which can differentiate into osteoblasts, chondrocytes and adipocytes.
      Dysfunction of BMSCs in response to pathological stimuli contributes to bone
      diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be
      an important mediator in bone formation and mineralization. The aim of this study
      was to investigate whether melatonin protected against iron overload-induced
      dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron
      overload induced by ferric ammonium citrate (FAC) caused irregularly
      morphological changes and markedly reduced the viability in BMSCs. Consistently,
      osteogenic differentiation of BMSCs was significantly inhibited by iron overload,
      but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore,
      exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin
      as well. Meanwhile, melatonin was able to counter the reduction in cell
      proliferation by iron overload in BMSCs. In addition, protective effects of
      melatonin on iron overload-induced dysfunction of BMSCs were abolished by its
      inhibitor luzindole. Also, melatonin protected BMSCs against iron overload
      induced ROS accumulation and membrane potential depolarization. Further study
      uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein
      expressions in BMSCs with iron overload. Collectively, melatonin plays a
      protective role in iron overload-induced osteogenic differentiation dysfunction
      and senescence through blocking ROS accumulation and p53/ERK/p38 activation.

PMID- 28500784
TI  - Nonablative fractional laser-assisted daylight photodynamic therapy with topical
      methyl aminolevulinate for moderate to severe facial acne vulgaris: Results of a
      randomized and comparative study.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been reported as an effective
      alternative treatment for patients with acne. PURPOSE: To evaluate the efficacy
      and safety of DL-PDT in moderate to severe acne and to compare outcomes with
      those of laser-assisted daylight photodynamic therapy. METHODS: Patients were
      randomly assigned to either a DL-PDT group (D group) or a fractional laser
      assisted DL-PDT group (F group). The outcomes were assessed by measuring acne
      lesion counts and severity grade at 4, 8, 12, and 16 weeks after therapy
      commenced. RESULTS: Twenty-eight subjects completed the study. Compared with
      baseline, the mean inflammatory lesion counts significantly decreased by 36.0% in
      the D group and 51.8% in the F group at 8 weeks (P<.001). The mean acne severity
      grades in both groups significantly decreased starting at 4 weeks (P=.012), and
      the beneficial effects lasted 16 weeks. CONCLUSION: DL-PDT with MAL shows
      clinically good responses to inflammatory lesions and is well tolerated in
      patients with moderate to severe acne.

PMID- 28500785
TI  - Don't Label Me: A Qualitative Study of Patients' Perceptions and Experiences of
      Sedation During Behavioral Emergencies in the Emergency Department.
AB  - OBJECTIVES: Behavioral emergencies are commonly seen in emergency departments
      (EDs). Acutely agitated patients can be difficult to manage and sedation may be
      required to decrease dangerous behavior and to ensure the safety of both the
      patient and the staff. While the experience of staff caring for this population
      has been reported, patients' experiences with their overall management remains
      unknown. We aimed to describe the perceptions and experiences of patients
      regarding the use of sedation during acute behavioral emergencies. METHODS: Face
      to-face semistructured interviews were conducted with adults aged 18 years or
      older, who had received parenteral sedative medication for the management of a
      behavioral emergency and were deemed capable to participate. The participants
      were asked about their experiences of receiving care in the ED during the episode
      and their perceptions of sedation. All interviews were transcribed verbatim and
      analyzed thematically. RESULTS: Data saturation was reached after 13 interviews.
      Two broad themes emerged: trusting relationships and needs or wants following
      sedation. A trusting relationship is built through 1) confidence in care, 2)
      sedation as an appropriate treatment, 3) insight into own behavior, and 4) humane
      treatment. Four subthemes of needs or wants were identified: 1) empathy, 2)
      debrief, 3) addressing concerns, and 4) follow-up. CONCLUSIONS: A trusting
      relationship was identified as crucial to minimize the negative impact of
      coercive measures used to manage behavioral emergencies. Participants expressed
      similar needs to patients presenting with medical problems. This study
      illustrates their needs for compassionate communication, adequate information
      about the treatment provided, and follow-up care.

PMID- 28500786
TI  - Dovitinib enhances temozolomide efficacy in glioblastoma cells.
AB  - The multikinase inhibitor and FDA-approved drug dovitinib (Dov) crosses the blood
      brain barrier and was recently used as single drug application in clinical trials
      for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in
      GB cells are unknown. We used GB patient cells and cell lines to show that Dov
      downregulated the stem cell protein Lin28 and its target high-mobility group
      protein A2 (HMGA2). The Dov-induced reduction in pSTAT3Tyr705 phosphorylation
      demonstrated that Dov negatively affects the STAT3/LIN28/Let-7/HMGA2 regulatory
      axis in GB cells. Consistent with the known function of LIN28 and HMGA2 in GB
      self-renewal, Dov reduced GB tumor sphere formation. Dov treatment also caused
      the downregulation of key base excision repair factors and O6 -methylguanine-DNA
      methyltransferase (MGMT), which are known to have important roles in the repair
      of temozolomide (TMZ)-induced alkylating DNA damage. Combined Dov/TMZ treatment
      enhanced TMZ-induced DNA damage as quantified by nuclear gammaH2AX foci and comet
      assays, and increased GB cell apoptosis. Pretreatment of GB cells with Dov ('Dov
      priming') prior to TMZ treatment reduced GB cell viability independent of p53
      status. Sequential treatment involving 'Dov priming' and alternating treatment
      cycles with TMZ and Dov substantially reduced long-term GB cell survival in MGMT+
      patient GB cells. Our results may have immediate clinical implications to improve
      TMZ response in patients with LIN28+ /HMGA2+ GB, independent of their MGMT
      methylation status.

PMID- 28500787
TI  - Corticosterone primes the neuroinflammatory response to Gulf War Illness-relevant
      organophosphates independently of acetylcholinesterase inhibition.
AB  - Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting veterans of
      the 1991 Gulf War. Among the symptoms of GWI are those associated with sickness
      behavior, observations suggestive of underlying neuroinflammation. We have shown
      that exposure of mice to the stress hormone, corticosterone (CORT), and to
      diisopropyl fluorophosphate (DFP), as a nerve agent mimic, results in marked
      neuroinflammation, findings consistent with a stress/neuroimmune basis of GWI.
      Here, we examined the contribution of irreversible and reversible
      acetylcholinesterase (AChE) inhibitors to neuroinflammation in our mouse model of
      GWI. Male C57BL/6J mice received 4 days of CORT (400 mg/L) in the drinking water
      followed by a single dose of chlorpyrifos oxon (CPO; 8 mg/kg, i.p.), DFP (4
      mg/kg, i.p.), pyridostigmine bromide (PB; 3 mg/kg, i.p.), or physostigmine (PHY;
      0.5 mg/kg, i.p.). CPO and DFP alone caused cortical and hippocampal
      neuroinflammation assessed by qPCR of tumor necrosis factor-alpha, IL-6, C-C
      chemokine ligand 2, IL-1beta, leukemia inhibitory factor and oncostatin M; CORT
      pretreatment markedly augmented these effects. Additionally, CORT exposure prior
      to DFP or CPO enhanced activation of the neuroinflammation signal transducer,
      signal transducer and activator of transcription 3 (STAT3). In contrast, PHY or
      PB alone or with CORT pretreatment did not produce neuroinflammation or STAT3
      activation. While all of the CNS-acting AChE inhibitors (DFP, CPO, and PHY)
      decreased brain AChE activity, CORT pretreatment abrogated these effects for the
      irreversible inhibitors. Taken together, these findings suggest that irreversible
      AChE inhibitor-induced neuroinflammation and particularly its exacerbation by
      CORT, result from non-cholinergic effects of these compounds, pointing
      potentially to organophosphorylation of other neuroimmune targets.

PMID- 28500788
TI  - Unraveling the importance of the malaria parasite helicases.
AB  - Malaria is a human parasitic disease caused by infection from Plasmodium species,
      particularly Plasmodium falciparum. Each year millions of people are infected
      with malaria and large numbers of deaths result due to this deadly infection. P.
      falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle
      in humans and mosquitoes. The control of malaria is still a challenge as the
      parasite is continuously developing resistance to available antimalarial drugs
      and the mosquito vector is developing resistance to insecticides. The
      availability of P. falciparum genome has resulted in the identification of
      parasite-specific proteins that can be targeted without harmful effects to the
      human host. Toward this goal, we have been working on the identification and
      characterization of helicases in order to find parasite-specific helicases, which
      can be used as novel drug targets to tackle the rising problem of drug
      resistance. Helicases are ATP-dependent nucleic acid unwinding enzymes. The P.
      falciparum genome analysis depicts that it contains some parasite-specific
      helicases and homologs to most of the human helicases. Here, we present an
      overview of P. falciparum helicases and their importance in parasite growth and
      survival.

PMID- 28500789
TI  - Atlantic small-mammal: a dataset of communities of rodents and marsupials of the
      Atlantic forests of South America.
AB  - The contribution of small mammal ecology to the understanding of macroecological
      patterns of biodiversity, population dynamics, and community assembly has been
      hindered by the absence of large datasets of small mammal communities from
      tropical regions. Here we compile the largest dataset of inventories of small
      mammal communities for the Neotropical region. The dataset reviews small mammal
      communities from the Atlantic forest of South America, one of the regions with
      the highest diversity of small mammals and a global biodiversity hotspot, though
      currently covering less than 12% of its original area due to anthropogenic
      pressures. The dataset comprises 136 references from 300 locations covering seven
      vegetation types of tropical and subtropical Atlantic forests of South America,
      and presents data on species composition, richness, and relative abundance
      (captures/trap-nights). One paper was published more than 70 yr ago, but 80% of
      them were published after 2000. The dataset comprises 53,518 individuals of 124
      species of small mammals, including 30 species of marsupials and 94 species of
      rodents. Species richness averaged 8.2 species (1-21) per site. Only two species
      occurred in more than 50% of the sites (the common opossum, Didelphis aurita and
      black-footed pigmy rice rat Oligoryzomys nigripes). Mean species abundance varied
      430-fold, from 4.3 to 0.01 individuals/trap-night. The dataset also revealed a
      hyper-dominance of 22 species that comprised 78.29% of all individuals captured,
      with only seven species representing 44% of all captures. The information
      contained on this dataset can be applied in the study of macroecological patterns
      of biodiversity, communities, and populations, but also to evaluate the
      ecological consequences of fragmentation and defaunation, and predict disease
      outbreaks, trophic interactions and community dynamics in this biodiversity
      hotspot.

PMID- 28500790
TI  - Accuracy evaluation of a six-degree-of-freedom couch using cone beam CT and
      IsoCal phantom with an in-house algorithm.
AB  - PURPOSE: The accuracy of a six degree of freedom (6DoF) couch was evaluated using
      a novel method. METHODS: Cone beam CT (CBCT) images of a 3D phantom (IsoCal) were
      acquired with different, known combinations of couch pitch and roll angles. Pitch
      and roll angles between the maximum allowable values of 357 and 3 degrees were
      tested in one degree increments. A total of 49 combinations were tested at 0
      degrees of yaw (couch rotation angle). The 3D positions of 16 tungsten carbide
      ball bearings (BBs), each 4 mm in diameter and arranged in a known geometry
      within the IsoCal phantom, were determined in the 49 image sets with in-house
      software. The BB positions at different rotation angles were determined using a
      rotation matrix from the original BB positions at zero pitch and roll angles. A
      linear least squares fit method estimated the rotation angles and differences
      between detected and nominal rotation angles were calculated. This study was
      conducted for the case with and without extra weight on the couch. Couch walk
      shifts for the system were investigated using eight combinations of rotation,
      roll and pitch. RESULTS: A total of 49 CBCT images with voxel sizes 0.5 * 0.5 *
      1.0 mm3 were taken for the case without extra weight on the couch. The 16 BBs
      were determined to evaluate the isocenter translation and rotation differences
      between the calculated and nominal couch values. Among all 49 calculations, the
      maximum rotation angle differences were 0.10 degrees for pitch, 0.15 degrees for
      roll and 0.09 degrees for yaw. The corresponding mean and standard deviation
      values were 0.028 +/- 0.032, -0.043 +/- 0.058, and -0.009 +/- 0.033 degrees. The
      maximum translation differences were 0.3 mm in the left-right direction, 0.5 mm
      in the anterior-posterior direction and 0.4 mm in the superior-inferior
      direction. The mean values and corresponding standard deviations were 0.07 +/-
      0.12, -0.05 +/- 0.25, and -0.12+/-0.14 mm for the planes described above. With an
      80 kg phantom on the couch, the maximum translation shift was 0.69 mm. The couch
      walk translation shifts were less than 0.1 mm and rotation shifts were less than
      0.1 degree. CONCLUSIONS: Errors of a new 6DoF couch were tested using CBCT images
      of a 3D phantom. The rotation errors were less than 0.3 degree and the
      translation errors were less than or equal to 0.8 mm in each direction. This
      level of accuracy is warranted for clinical radiotherapy utilization including
      stereotactic radiosurgery.

PMID- 28500791
TI  - Fire catalyzed rapid ecological change in lowland coniferous forests of the
      Pacific Northwest over the past 14,000 years.
AB  - Disturbance can catalyze rapid ecological change by causing widespread mortality
      and initiating successional pathways, and during times of climate change,
      disturbance may contribute to ecosystem state changes by initiating a new
      successional pathway. In the Pacific Northwest of North America (PNW),
      disturbance by wildfires strongly shapes the composition and structure of lowland
      forests, but understanding the role of fire over periods of climate change is
      challenging, because fire-return intervals are long (e.g., millennia) and the
      coniferous trees dominating these forests can live for many centuries. We
      developed stand-scale paleorecords of vegetation and fire that span nearly the
      past 14,000 yr to study how fire was associated with state changes and rapid
      dynamics in forest vegetation at the stand scale (1-3 ha). We studied forest
      history with sediment cores from small hollow sites in the Marckworth State
      Forest, located ~1 km apart in the Tsuga heterophylla Zone in the Puget Lowland
      ecoregion of western Washington, USA. The median rate of change in pollen/spore
      assemblages was similar between sites (0.12 and 0.14% per year), but at both
      sites, rates of change increased significantly following fire events (ranging up
      to 1% per year, with a median of 0.28 and 0.38%, P < 0.003). During times of low
      climate velocity, forest composition was resilient to fires, which initiated
      successional pathways leading back to the dominant vegetation type. In contrast,
      during times of high climate variability and velocity (e.g., the early Holocene)
      forests were not resilient to fires, which triggered large-scale state changes.
      These records provide clear evidence that disturbance, in the form of an
      individual fire event, can be an important catalyst for rapid state changes,
      accelerating vegetation shifts in response to large-scale climate change.

PMID- 28500792
TI  - Changing trends in the aetiology, treatment and outcomes of bloodstream infection
      occurring in the first year after solid organ transplantation: a single-centre
      prospective cohort study.
AB  - To analyse trends in the aetiology, treatment and outcomes of bloodstream
      infection (BSI) within the first year post-transplant over the last 10-year
      period, we prospectively recorded all episodes of BSI occurring in solid organ
      transplant (SOT) recipients during the first year post-transplant from 2007 to
      2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive
      episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram
      positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady
      increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due
      to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%).
      Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically,
      especially due to extended-spectrum beta-lactamase (ESBL) production (7.1-34.7%).
      There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%;
      P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In
      conclusion, today, GNB are the leading causative agents of BSI in SOT recipients
      within the first year after SOT. In addition, MDR GNB have emerged mainly due to
      ESBL-producing strains. In spite of these changes, length of hospital stay, days
      of treatment and mortality have remained stable over time.

PMID- 28500793
TI  - Integrating the genomic architecture of human nucleolar organizer regions with
      the biophysical properties of nucleoli.
AB  - Nucleoli are the sites of ribosome biogenesis and the largest membraneless
      subnuclear structures. They are intimately linked with growth and proliferation
      control and function as sensors of cellular stress. Nucleoli form around arrays
      of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs).
      In humans, NORs are located on the short arms of all five human acrocentric
      chromosomes. Multiple NORs contribute to the formation of large heterochromatin
      surrounded nucleoli observed in most human cells. Here we will review recent
      findings about their genomic architecture. The dynamic nature of nucleoli began
      to be appreciated with the advent of photodynamic experiments using fluorescent
      protein fusions. We review more recent data on nucleoli in Xenopus germinal
      vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates
      nucleolar fusion. Further analysis in both XenopusGVs and Drosophila embryos
      indicates that the internal organization of nucleoli is generated by a
      combination of liquid-liquid phase separation and active processes involving
      rDNA. We will attempt to integrate these recent findings with the genomic
      architecture of human NORs to advance our understanding of how nucleoli form and
      respond to stress in human cells.

PMID- 28500794
TI  - Rapid, broad-scale gene expression evolution in experimentally harvested fish
      populations.
AB  - Gene expression changes potentially play an important role in adaptive evolution
      under human-induced selection pressures, but this has been challenging to
      demonstrate in natural populations. Fishing exhibits strong selection pressure
      against large body size, thus potentially inducing evolutionary changes in life
      history and other traits that may be slowly reversible once fishing ceases.
      However, there is a lack of convincing examples regarding the speed and magnitude
      of fisheries-induced evolution, and thus, the relevant underlying molecular-level
      effects remain elusive. We use wild-origin zebrafish (Danio rerio) as a model for
      harvest-induced evolution. We experimentally demonstrate broad-scale gene
      expression changes induced by just five generations of size-selective harvesting,
      and limited genetic convergence following the cessation of harvesting. We also
      demonstrate significant allele frequency changes in genes that were
      differentially expressed after five generations of size-selective harvesting. We
      further show that nine generations of captive breeding induced substantial gene
      expression changes in control stocks likely due to inadvertent selection in the
      captive environment. The large extent and rapid pace of the gene expression
      changes caused by both harvest-induced selection and captive breeding emphasizes
      the need for evolutionary enlightened management towards sustainable fisheries.

PMID- 28500795
TI  - The future distribution of river fish: The complex interplay of climate and land
      use changes, species dispersal and movement barriers.
AB  - The future distribution of river fishes will be jointly affected by climate and
      land use changes forcing species to move in space. However, little is known
      whether fish species will be able to keep pace with predicted climate and land
      use-driven habitat shifts, in particular in fragmented river networks. In this
      study, we coupled species distribution models (stepwise boosted regression trees)
      of 17 fish species with species-specific models of their dispersal (fish
      dispersal model FIDIMO) in the European River Elbe catchment. We quantified (i)
      the extent and direction (up- vs. downstream) of predicted habitat shifts under
      coupled "moderate" and "severe" climate and land use change scenarios for 2050,
      and (ii) the dispersal abilities of fishes to track predicted habitat shifts
      while explicitly considering movement barriers (e.g., weirs, dams). Our results
      revealed median net losses of suitable habitats of 24 and 94 river kilometers per
      species for the moderate and severe future scenarios, respectively. Predicted
      habitat gains and losses and the direction of habitat shifts were highly variable
      among species. Habitat gains were negatively related to fish body size, i.e.,
      suitable habitats were projected to expand for smaller-bodied fishes and to
      contract for larger-bodied fishes. Moreover, habitats of lowland fish species
      were predicted to shift downstream, whereas those of headwater species showed
      upstream shifts. The dispersal model indicated that suitable habitats are likely
      to shift faster than species might disperse. In particular, smaller-bodied fish
      (<200 mm) seem most vulnerable and least able to track future environmental
      change as their habitat shifted most and they are typically weaker dispersers.
      Furthermore, fishes and particularly larger-bodied species might substantially be
      restricted by movement barriers to respond to predicted climate and land use
      changes, while smaller-bodied species are rather restricted by their specific
      dispersal ability.

PMID- 28500796
TI  - High-density genotyping of the A.E. Watkins Collection of hexaploid landraces
      identifies a large molecular diversity compared to elite bread wheat.
AB  - The importance of wheat as a food crop makes it a major target for agricultural
      improvements. As one of the most widely grown cereal grains, together with maize
      and rice, wheat is the leading provider of calories in the global diet,
      constituting 29% of global cereal production in 2015. In the last few decades,
      however, yields have plateaued, suggesting that the green revolution, at least
      for wheat, might have run its course and that new sources of genetic variation
      are urgently required. The overall aim of our work was to identify novel
      variation that may then be used to enable the breeding process. As landraces are
      a potential source of such diversity, here we have characterized the A.E. Watkins
      Collection alongside a collection of elite accessions using two complementary
      high-density and high-throughput genotyping platforms. While our results show the
      importance of using the appropriate SNP collection to compare diverse accessions,
      they also show that the Watkins Collection contains a substantial amount of novel
      genetic diversity which has either not been captured in current breeding
      programmes or which has been lost through previous selection pressures. As a
      consequence of our analysis, we have identified a number of accessions which
      carry an array of novel alleles along with a number of interesting chromosome
      rearrangements which confirm the variable nature of the wheat genome.

PMID- 28500798
TI  - Persistent Sick Sinus Syndrome in Scrub Typhus.

PMID- 28500797
TI  - Fatal Flea-Borne Typhus in Texas: A Retrospective Case Series, 1985-2015.
AB  - AbstractFlea-borne (murine) typhus is a global rickettsiosis caused by Rickettsia
      typhi. Although flea-borne typhus is no longer nationally notifiable, cases are
      reported for surveillance purposes in a few U.S. states. The infection is
      typically self-limiting, but may be severe or life-threatening in some patients.
      We performed a retrospective review of confirmed or probable cases of fatal flea
      borne typhus reported to the Texas Department of State Health Services during
      1985-2015. When available, medical charts were also examined. Eleven cases of
      fatal flea-borne typhus were identified. The median patient age was 62 years
      (range, 36-84 years) and 8 (73%) were male. Patients presented most commonly with
      fever (100%), nausea and vomiting (55%), and rash (55%). Respiratory (55%) and
      neurologic (45%) manifestations were also identified frequently. Laboratory
      abnormalities included thrombocytopenia (82%) and elevated hepatic transaminases
      (63%). Flea or animal contact before illness onset was frequently reported (55%).
      The median time from hospitalization to administration of a tetracycline-class
      drug was 4 days (range, 0-5 days). The median time from symptom onset to death
      was 14 days (range, 1-34 days). Flea-borne typhus can be a life-threatening
      disease if not treated in a timely manner with appropriate tetracycline-class
      antibiotics. Flea-borne typhus should be considered in febrile patients with
      animal or flea exposure and respiratory or neurologic symptoms of unknown
      etiology.

PMID- 28500799
TI  - Erratum.

PMID- 28500800
TI  - First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug
      Resistant Mycobacterium tuberculosis in Saudi Arabia.
AB  - AbstractIn Saudi Arabia, there were no nationwide screening studies conducted so
      far to determine the aminoglycoside and fluoroquinolone resistance among
      multidrug-resistant tuberculosis (MDR-TB) isolates. Therefore, as the first
      attempt in the country, a retrospective analysis has been conducted on a
      nationwide collection of 2,956 M. tuberculosis clinical isolates screened with
      phenotypic drug susceptibility testing to define MDR-TB. Enrolled MDR-TB isolates
      were subjected to second-line drug susceptibility testing, detection of mutations
      conferring resistance to aminoglycosides and fluoroquinolone, followed by 24-loci
      mycobacterial interspersed repetitive unit-variable number of tandem repeat
      typing and spoligotyping. Overall, 83 isolates were identified as MDR-TB, and 13
      (15.7%) isolates showed resistance to second-line drugs. Moxifloxacin (low level)
      showed higher resistant rates (10.8%) followed by ofloxacin (7.2%), capreomycin
      (3.6%), kanamycin (3.6%), and amikacin (2.4%). Overall fluoroquinolone resistance
      was 12%, whereas aminoglycoside resistance was 7.2%. Predominant mutations
      conferring resistance to fluoroquinolone were found in gyrA A90V and D94G,
      whereas aminoglycoside resistance was observed only with rrs gene A1401G
      mutation. The corresponding strain lineages predominated with Indo-Oceanic and
      East-African Indian origin. Interestingly, none of the isolates with second-line
      drug resistance was defined as extensively drug-resistant TB (XDR-TB).
      Surprisingly, many isolates (50.6%) were panresistant to first-line drugs. Saudi
      Arabia faces considerable burden of fluoroquinolone- and aminoglycoside-resistant
      MDR-TB. Higher incidence of panresistant MDR-TB reveals a threat for the
      emergence of XDR-TB strains in the near future.

PMID- 28500801
TI  - A Malaria-Resistant Phenotype with Immunological Correlates in a Tanzanian Birth
      Cohort Exposed to Intense Malaria Transmission.
AB  - AbstractMalaria incidence is highly heterogeneous even in areas of high
      transmission, although no conclusive evidence exists that innate or naturally
      acquired resistance can prevent infection over an extended period of time. This
      longitudinal study examined immunoparasitological evidence for a malaria
      resistant phenotype in which children do not develop malaria despite an extended
      period of exposure to parasites. Within a birth cohort followed from 2002 to 2006
      in Muheza, Tanzania, an area of intense transmission, children (N = 687) provided
      blood smears biweekly during infancy and monthly thereafter. Maternal and
      childhood characteristics were obtained, cord-blood cytokines were measured, and
      antibody responses were assayed as measures of stage-specific exposure. Sixty
      three (9.2%) children had no blood smear-positive slides over 2 years of follow
      up (range: 1-3.5 years) and were identified as malaria resistant. Malaria
      resistant children were similar to other children with respect to completeness of
      follow-up and all maternal and childhood characteristics except residence area.
      Antibody seroprevalence was similar for two sporozoite antigens, but malaria
      resistant children had a lower antibody seroprevalence to merozoite antigens
      merozoite surface protein 1 (5.4% versus 30.2%; P < 0.0001) and apical membrane
      antigen 1 (7.2% versus 33.3%; P < 0.0001). Malaria-resistant children had higher
      cytokine levels in cord blood, particularly interleukin-1beta. In summary, a
      subset of children living in an area of intense transmission was exposed to
      malaria parasites, but never developed patent parasitemia; this phenotype was
      associated with a distinct cytokine profile at birth and antibody profile during
      infancy. Further research with malaria-resistant children may identify mechanisms
      for naturally acquired immunity.

PMID- 28500802
TI  - High-Resolution Melting Curve Analysis of the 16S Ribosomal Gene to Detect and
      Identify Pathogenic and Saprophytic Leptospira Species in Colombian Isolates.
AB  - AbstractIt is important to identify the circulating Leptospira agent to enhance
      the performance of serodiagnostic tests by incorporating specific antigens of
      native species, develop vaccines that take into account the species/serovars
      circulating in different regions, and optimize prevention and control strategies.
      The objectives of this study were to develop a polymerase chain reaction (PCR)
      high-resolution melting (HRM) assay for differentiating between species of the
      genus Leptospira and to verify its usefulness in identifying unknown samples to
      species level. A set of primers from the initial region of the 16S ribosomal gene
      was designed to detect and differentiate the 22 species of Leptospira. Eleven
      reference strains were used as controls to establish the reference species and
      differential melting curves. Twenty-five Colombian Leptospira isolates were
      studied to evaluate the usefulness of the PCR-HRM assay in identifying unknown
      samples to species level. This identification was confirmed by sequencing and
      phylogenetic analysis of the 16S ribosomal gene. Eleven Leptospira species were
      successfully identified, except for Leptospira meyeri/Leptospira yanagawae
      because the sequences were 100% identical. The 25 isolates from humans, animals,
      and environmental water sources were identified as Leptospira santarosai
      (twelve), Leptospira interrogans (nine), and L. meyeri/L. yanagawae (four). The
      species verification was 100% concordant between PCR-HRM and phylogenetic
      analysis of the 16S ribosomal gene. The PCR-HRM assay designed in this study is a
      useful tool for identifying Leptospira species from isolates.

PMID- 28500803
TI  - Patients' Delay in Seeking Health Care for Tuberculosis Diagnosis in East Gojjam
      Zone, Northwest Ethiopia.
AB  - AbstractPatients' delay in seeking diagnosis is a major problem in the management
      of tuberculosis (TB). Relative to the burden of TB, there is lack of data on the
      magnitude of delays in seeking care and why patients fail to seek early care at
      health facilities in Ethiopia. A facility-based cross-sectional study was
      conducted from April to July 2013 in East Gojjam Zone, Amhara, Ethiopia, to
      assess patients' delays and associated factors in TB patients. Using simple
      random sampling, 605 (327 male and 278 female) participants were recruited. Of
      the total, 323 (53.4%) TB patients were delayed in seeking health care (median =
      45 days; mean = 78.5 days). The following independent variables were associated
      with patient delays: age >= 45 years (adjusted odds ratio [AOR] = 8.74, 95%
      confidence interval [CI] = 4.71-16.23, P < 0.001); working as a farmer (AOR =
      4.18, 95% CI = 1.44-12.11, P = 0.009); prior visit to holy water sites,
      traditional healers, and/or private drug shops (AOR = 69.11, 95% CI =13.91
      343.29, P < 0.001; AOR = 14.74, 95% CI = 1.43-152.31, P = 0.024; AOR = 2.10, 95%
      CI = 1.22-3.59, P = 0.007, respectively); poor knowledge about TB (AOR = 2.79,
      95% CI = 1.74-4.92, P = 0.006), and extrapulmonary TB (AOR = 14.69, 95% CI = 8.21
      26.26, P < 0.001). Generally, patients' delay in seeking care at health
      facilities was high (53.4%). Most of TB patients getting treatment from holy
      water (95.3%; 101/106) and traditional healers (84.6%; 11/13) were delayed.
      Therefore, for early seeking in modern health care, a combination of
      interventions is required to encourage TB patients.

PMID- 28500804
TI  - A Large Outbreak of Thiamine Deficiency Among Illegal Gold Miners in French
      Guiana.
AB  - From September 2013 to July 2014, several gold miners working in the tropical
      forest consulted the Maripasoula Health Center in French Guiana for edema and
      findings consistent with right-sided cardiac failure. Of the 42 cases of beriberi
      that were diagnosed, one patient died. The laboratory and clinical investigation
      demonstrated vitamin B1 deficiency in most of the patients tested. Furthermore,
      30 of 42 patients responded favorably to 500 mg of intravenous or intramuscular
      thiamine supplementation. In addition, dietary investigation showed insufficient
      thiamine intake in these patients. We concluded that patients had acquired
      beriberi because of diet restrictions, hard labor, and infectious diseases,
      notably malaria. In 2016, cases were still being reported. We recommend screening
      for compatible symptoms in gold miners, thiamine supplementation, and nutritional
      intervention.

PMID- 28500805
TI  - Unusual Otolaryngologic Manifestations of Paracoccidioidomycosis: A Case Report
      and Review of Literature.
AB  - AbstractParacoccidioidomycosis is a systemic mycosis caused by Paracoccidioides
      brasiliensis. It occurs more frequently in its chronic form, which particularly
      affects male adults from rural areas. These patients present with pulmonary
      involvement and systemic symptoms. Skin and mucosal lesions are rather typical
      and might suggest the diagnosis. The involvement of the upper airway mucosa is
      common and the patients usually complain of dysphagia and dysphonia. Nonetheless,
      in endemic areas, physicians should maintain a high level of suspicion even when
      faced with some atypical symptoms. We present the case of an adult diagnosed with
      nasopharyngeal paracoccidioidomycosis after presenting with an unusual
      otolaryngologic syndrome including unilateral soft palate paralysis with
      velopharyngeal insufficiency and hearing loss secondary to middle ear effusion.

PMID- 28500807
TI  - The Eyes Have It-Or Do They?

PMID- 28500808
TI  - Seroprevalence of Scrub Typhus, Typhus, and Spotted Fever Among Rural and Urban
      Populations of Northern Vietnam.
AB  - AbstractRickettsial infections are recognized as important causes of fever
      throughout southeast Asia. Herein, we determined the seroprevalence to
      rickettsioses within rural and urban populations of northern Vietnam. Prevalence
      of individuals with evidence of prior rickettsial infections (IgG positive) was
      surprisingly low, with 9.14% (83/908) testing positive to the three major
      rickettsial serogroups thought to circulate in the region. Prevalence of typhus
      group rickettsiae (TG)-specific antibodies (6.5%, 58/908) was significantly
      greater than scrub typhus group orientiae (STG)- or spotted fever group
      rickettsiae (SFG)-specific antibodies (P < 0.05). The majority of TG
      seropositives were observed among urban rather than rural residents (P < 0.05).
      In contrast, overall antibody prevalence to STG and SFG were both very low (1.1%,
      10/908 for STG; 1.7%, 15/908 for SFG), with no significant differences between
      rural and urban residents. These results provide data on baseline population
      characteristics that may help inform development of Rickettsia serological
      testing criteria in future clinical studies.

PMID- 28500809
TI  - Investigating Mumps Outbreak in Odisha, India: An Opportunity to Assess the
      Health System by Utilizing the Essential Public Health Services Framework.
AB  - AbstractMumps, a highly contagious, viral disease continues to spread in India,
      despite the availability of an effective vaccine. On November 24, 2014, we came
      across a suspected case of mumps in a 6-year-old boy in a village of Bhusandapur
      sector in Odisha. We initiated an outbreak investigation using standard
      techniques outlined by the Centers for Disease Control and Prevention, Atlanta,
      GA. This uncovered a silent epidemic of 94 case patients (10% of the population)
      over a period of 16 weeks between August and December 2014, in a single village,
      which had gone completely unnoticed by the existing health-care system. Since the
      index case was one of the last case patients of the outbreak, investigation for
      immediate control was not a priority. Hence, we have used this exercise to
      describe the outbreak and identify causes that led to its nondetection. Age range
      of the case patients was between 2 and 40 years; 85 (90.4%) case patients were <=
      15 years of age and 54 (57.4%) were females. Average duration of illness was 9
      days. No child had received the mumps vaccine. The outbreak had led to a
      community expenditure of 538 USD. The exercise uncovered a number of weak links
      in the essential public health services within the health-care delivery system in
      the area.

PMID- 28500806
TI  - Antibody Responses to Plasmodium falciparum and Plasmodium vivax and Prospective
      Risk of Plasmodium spp. Infection Postpartum.
AB  - AbstractPostpartum women may have an altered susceptibility to Plasmodium
      falciparum and Plasmodium vivax. The relationship between naturally acquired
      malarial immunity and susceptibility to malaria postpartum is yet to be
      determined. IgG levels were measured against P. falciparum and P. vivax antigens
      from delivery in 201 postpartum and 201 nonpregnant controls over 12 weeks.
      Associations between time-varying antibody levels and time to first
      microscopically confirmed species-specific infection were determined by Cox
      regression. Associations between antibody levels and prospective risk of
      Plasmodium infection were similar in postpartum and control women. A 2-fold
      increase in P. falciparum antibody levels was associated with increased
      prospective risk of P. falciparum infection (hazard ratio [HR] range = 1.37
      1.94). Antibody levels against most P. vivax antigens displayed no association
      with prospective risk of P. vivax infection (HR range = 1.02-1.05) with the
      exception of PvMSP119 antibodies that were weakly associated with prospective
      risk of P. vivax infection (HR = 1.14 (95% confidence interval = 1.02, 1.28) per
      2-fold increase in levels). Associations between antibody levels and prospective
      risk of infection attenuated when adjusted for documented retrospective exposure.
      Serology may be a useful tool to predict and monitor women at increased risk of
      P. falciparum infection postpartum, particularly in the absence of a detailed
      history of retrospective infections.

PMID- 28500810
TI  - Environmental and Behavioral Drivers of Buruli Ulcer Disease in Selected
      Communities Along the Densu River Basin of Ghana: A Case-Control Study.
AB  - AbstractThe exact route of transmission of Mycobacterium ulcerans (MU) (causative
      agent of Buruli ulcer [BU]), risk factors, and reservoir hosts are not clearly
      known, although it has been identified as an environmental pathogen. This study
      assessed potential environmental and behavioral risk factors that influence BU
      infections. We conducted a case-control study where cases were matched by their
      demographic characteristics and place of residence. A structured questionnaire
      was administered to solicit information on the environmental and behavioral
      factors of participants that may expose them to infection. A total of 176 cases
      and 176 controls were enrolled into the study. Multivariate conditional logistic
      regression analysis identified farming in swampy areas (odds ratio [OR] = 4.10,
      95% confidence interval [CI] = 3.82-7.18), farming while wearing short clothing
      (OR = 1,734.1, 95% CI = 68.1-44,120.9), insect bite (OR = 988.3, 95% CI = 31.4
      31,115.6), and application of leaves on wounds (OR = 6.23, 95% CI = 4.74-18.11)
      as potential risk factors. Farming in long clothing (OR = 0.000, 95% CI = 0.00
      0.14), washing wound with water and soap (OR = 0.37, 95% CI = 0.29-0.98), and
      application of adhesive bandage on wounds (OR = 0.31, 95% CI = 0.15-0.82) were
      found to be protective against BU infection. In the absence of the exact MU
      transmission mechanisms, education of public in BU-endemic zones on the use of
      protective clothing during farming activities to limit exposure of the skin and
      proper wound care management would be essential in the fight against BU.

PMID- 28500812
TI  - The Prevalence of Chagas Disease Among Latin American Immigrants with Pacemakers
      in Los Angeles, California.
AB  - AbstractChagas disease (CD), with associated conduction abnormalities, is a
      common indication for pacemaker implantation in Latin America. The prevalence of
      CD in Latin American immigrants with pacemakers residing in the United States has
      never been studied. This single-center cross-sectional study included pacemaker
      patients who were aged 18 years or more with a previous residence in Latin
      America for at least 6 months. Patients with an implantable cardioverter
      defibrillator, cardiac resynchronization therapy, or iatrogenic and/or congenital
      heart block were excluded. Serological testing for Trypanosoma cruzi was
      performed at enrollment. A total of 80 patients were enrolled, and CD was
      diagnosed in six patients (7.5%). Patients with CD were more likely to be from El
      Salvador (P = 0.001). Other clinical, therapeutic, electrocardiographic, and
      echocardiographic variables were similar between the CD and non-CD groups. There
      is a high prevalence of CD among Latin American immigrants with pacemakers in Los
      Angeles.

PMID- 28500811
TI  - Cost-Effectiveness of Dengue Vaccination Programs in Brazil.
AB  - AbstractThe first approved dengue vaccine, CYD-TDV, a chimeric, live-attenuated,
      tetravalent dengue virus vaccine, was recently licensed in 13 countries,
      including Brazil. In light of recent vaccine approval, we modeled the cost
      effectiveness of potential vaccination policies mathematically based on data from
      recent vaccine efficacy trials that indicated that vaccine efficacy was lower in
      seronegative individuals than in seropositive individuals. In our analysis, we
      investigated several vaccination programs, including routine vaccination, with
      various vaccine coverage levels and those with and without large catch-up
      campaigns. As it is unclear whether the vaccine protects against infection or
      just against disease, our model incorporated both direct and indirect effects of
      vaccination. We found that in the presence of vaccine-induced indirect
      protection, the cost-effectiveness of dengue vaccination decreased with
      increasing vaccine coverage levels because the marginal returns of herd immunity
      decreases with vaccine coverage. All routine dengue vaccination programs that we
      considered were cost-effective, reducing dengue incidence significantly.
      Specifically, a routine dengue vaccination of 9-year-olds would be cost-effective
      when the cost of vaccination per individual is less than $262. Furthermore, the
      combination of routine vaccination and large catch-up campaigns resulted in a
      greater reduction of dengue burden (by up to 93%) than routine vaccination alone,
      making it a cost-effective intervention as long as the cost per course of
      vaccination is $255 or less. Our results show that dengue vaccination would be
      cost-effective in Brazil even with a relatively low vaccine efficacy in
      seronegative individuals.

PMID- 28500813
TI  - Quality of Case Management for Pneumonia and Diarrhea Among Children Seen at
      Health Facilities in Southern Malawi.
AB  - Pneumonia and diarrhea are leading causes of child deaths in Malawi. Guidelines
      to manage childhood illnesses in resource-poor settings exist, but studies have
      reported low health-care worker (HCW) adherence to guidelines. We conducted a
      health facility survey from January to March 2015 to assess HCW management of
      pneumonia and diarrhea in children < 5 years of age in southern Malawi, and to
      determine factors associated with case management quality. Descriptive statistics
      and multivariable logistic regression models examined patient, HCW, and health
      facility factors associated with recommended pneumonia and diarrhea management,
      using Malawi's national guidelines as the gold standard. Of 694 surveyed children
      2-59 months of age at 95 health facilities, 132 (19.0%) met survey criteria for
      pneumonia; HCWs gave recommended antibiotic treatment to 90 (68.2%). Of 723
      children < 5 years of age, 222 (30.7%) had uncomplicated diarrhea; HCWs provided
      recommended treatment to 94 (42.3%). In multivariable analyses, caregivers'
      spontaneous report of children's symptoms was associated with recommended
      treatment of both pneumonia (odds ratio [OR]: 2.8, 95% confidence interval [CI]:
      1.2-6.8, P = 0.023) and diarrhea (OR: 24.2, 95% CI: 6.0-97.0, P < 0001). Malaria
      diagnosis was negatively associated with recommended treatment (OR for pneumonia:
      0.5, 95% CI: 0.2-1.0, P = 0.046; OR for diarrhea: 0.3, 95% CI: 0.1-0.6, P =
      0.003). To improve quality of care, children should be assessed systematically,
      even when malaria is suspected. Renewed efforts to invigorate such a systematic
      approach, including HCW training, regular follow-up supervision, and monitoring
      HCW performance, are needed in Malawi.

PMID- 28500814
TI  - FTA Cards Facilitate Storage, Shipment, and Detection of Arboviruses in Infected
      Aedes aegypti Collected in Adult Mosquito Traps.
AB  - AbstractThe utility of applying infected Aedes aegypti to Flinders Technology
      Associates (FTA(r)) cards for storage, transport, and detection of dengue, Zika,
      and Barmah Forest viruses was assessed in laboratory-based experiments. The
      mosquitoes had been removed from Gravid Aedes Traps maintained under conditions
      of high temperature and humidity. RNA of all viruses could be detected in
      infected mosquitoes on FTA cards either individually or in pools with uninfected
      mosquitoes, and stored for up to 28 days. Importantly, there was only a minimal
      decrease in RNA levels in mosquitoes between days 0 and 28, indicating that viral
      RNA was relatively stable on the cards. FTA cards thus provide a mechanism for
      storing potentially infected mosquitoes collected in the field and transporting
      them to a central diagnostic facility for virus detection.

PMID- 28500815
TI  - Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for
      Cutaneous Leishmaniasis.
AB  - AbstractCutaneous leishmaniasis (CL) by Leishmania braziliensis is associated
      with decreasing cure rates in Brazil. Standard treatment with pentavalent
      antimony (Sbv) cures only 50-60% of the cases. The immunopathogenesis of CL ulcer
      is associated with high interferon-gamma and tumor necrosis factor (TNF)
      production. Pentoxifylline, a TNF inhibitor, has been successfully used in
      association with Sbv in mucosal and cutaneous leishmaniasis. This randomized,
      double-blind, and placebo-controlled trial aimed to evaluate the efficacy and
      safety of oral pentoxifylline plus Sbv versus placebo plus Sbv in patients with
      CL in Bahia, Brazil. A total of 164 patients were randomized in two groups to
      receive the combination or the monotherapy. Cure rate 6 months after treatment
      was 45% in the pentoxifylline group and 43% in the control group. There was also
      no difference between the groups regarding the healing time (99.7 +/- 66.2 days
      and 98.1 +/- 72.7 days, respectively). Adverse events were more common in the
      pentoxifylline group (37.8%), versus 23% in the placebo group. This trial shows
      that Sbv combined therapy with pentoxifylline is not more effective than Sbv
      monotherapy in the treatment of CL caused by L. braziliensis.

PMID- 28500817
TI  - Transmission Incompetence of Culex quinquefasciatus and Culex pipiens pipiens
      from North America for Zika Virus.
AB  - AbstractIn late 2014, Zika virus (ZIKV; Flaviviridae, Flavivirus) emerged as a
      significant arboviral disease threat in the Western hemisphere. Aedes aegypti and
      Aedes albopictus have been considered the principal vectors of ZIKV in the New
      World due to viral isolation frequency and vector competence assessments. Limited
      reports of Culex transmission potential have highlighted the need for additional
      vector competence assessments of North American Culex species. Accordingly, North
      American Culex pipiens and Culex quinquefasciatus were orally exposed and
      intrathoracically inoculated with the African prototype ZIKV strain and currently
      circulating Asian lineage ZIKV strains to assess infection, dissemination, and
      transmission potential. Results indicated that these two North American Culex
      mosquito species were highly refractory to oral infection with no dissemination
      or transmission observed with any ZIKV strains assessed. Furthermore, both Culex
      mosquito species intrathoracically inoculated with either Asian or African
      lineage ZIKVs failed to expectorate virus in saliva. These in vivo results were
      further supported by the observation that multiple mosquito cell lines of Culex
      species origin demonstrated significant growth restriction of ZIKV strains
      compared with Aedes-derived cell lines. In summation, no evidence for the
      potential of Cx. pipiens or Cx. quinquefasciatus to serve as a competent vector
      for ZIKV transmission in North America was observed.

PMID- 28500819
TI  - Primary Pancreatic Hydatid: A Rare Cystic Lesion of the Pancreas.

PMID- 28500816
TI  - Serum Lipids and Lipoproteins During Uncomplicated Malaria: A Cohort Study in
      Lambarene, Gabon.
AB  - AbstractThe serum lipid profile in malaria patients has been found to differ from
      that of healthy controls. We investigated serum lipid profile changes in malaria
      patients over time compared with patients with other febrile diseases. In total,
      217 patients were included in the study (111 malaria patients and 106 symptomatic
      controls, defined as malaria-negative febrile patients). Serum lipid levels
      (mmol/L) were significantly lower in malaria patients compared with those with
      other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94]
      versus 3.97 [1.22; P < 0.001]; high-density lipoprotein cholesterol [HDL-C] =
      0.43 [0.47] versus 1.05 [0.67; P < 0.001], low-density lipoprotein cholesterol
      [LDL-C] = 2.05 [0.76] versus 2.42 [0.90; P < 0.001]. Triglycerides (TGs) levels
      were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; P < 0.001]). No
      significant differences were found for apolipoprotein A1, apolipoprotein B, and
      lipoprotein(a). Cholesterol levels increased toward reference values on day 28
      (TC = 3.26-3.98, P < 0.001; HDL-C = 0.43-0.96, P < 0.001; LDL-C = 2.05-2.60, P <
      0.001). TG levels decreased from 1.81 on admission to 1.76 (day 3) and 0.88 (day
      28; P = 0.130). Lipid profile changes were not correlated with parasitemia or
      Plasmodium falciparum histidine-rich protein 2 levels. This study confirms
      characteristic temporary lipid profile changes in malaria. Lipid profile changes
      demonstrated a good accuracy to discriminate between malaria and other febrile
      diseases (area under the curve = 0.80 (95% confidence interval = 0.742-0.863, P <
      0.001). Several plausible hypotheses exist regarding the pathophysiology of lipid
      profile changes in malaria. Further studies to elucidate the precise pathways may
      lead to improved understanding of the underlying pathophysiology.

PMID- 28500818
TI  - Household Microbial Water Quality Testing in a Peruvian Demographic and Health
      Survey: Evaluation of the Compartment Bag Test for Escherichia coli.
AB  - AbstractThe Joint Monitoring Program relies on household surveys to classify
      access to improved water sources instead of measuring microbiological quality.
      The aim of this research was to pilot a novel test for Escherichia coli
      quantification of household drinking water in the 2011 Demographic and Health
      Survey (DHS) in Peru. In the Compartment Bag Test (CBT), a 100-mL water sample is
      supplemented with chromogenic medium to support the growth of E. coli, poured
      into a bag with compartments, and incubated. A color change indicates E. coli
      growth, and the concentration of E. coli/100 mL is estimated as a most probable
      number. Triplicate water samples from 704 households were collected; one sample
      was analyzed in the field using the CBT, another replicate sample using the CBT
      was analyzed by reference laboratories, and one sample using membrane filtration
      (MF) was analyzed by reference laboratories. There were no statistically
      significant differences in E. coli concentrations between the field and
      laboratory CBT results, or when compared with MF results. These results suggest
      that the CBT for E. coli is an effective method to quantify fecal bacteria in
      household drinking water. The CBT can be incorporated into DHS and other national
      household surveys as a direct measure of drinking water safety based on microbial
      quality to better document access to safe drinking water.

PMID- 28500820
TI  - Jared Diamond Confidential Reflections on Writing, Science, and Life.

PMID- 28500822
TI  - Erratum.

PMID- 28500821
TI  - Serum Carbonic Anhydrase 1 is a Biomarker for Diagnosis of Human Schistosoma
      mansoni Infection.
AB  - AbstractSchistosoma mansoni is a major public health threat in many parts of the
      world. The current diagnostic tests for schistosomiasis are suboptimal,
      particularly early in infection, when the parasite burden is low and with
      reinfection after treatment. We sought to identify novel biomarkers of active
      infection by studying serum proteins in a mouse model of schistosomiasis followed
      by confirmation in chronically infected patients. Acute (6 weeks) and chronic (12
      weeks) sera from S. mansoni-infected C57Bl/6 mice as well as sera from
      chronically infected patients were assessed using two proteomic platforms:
      surface-enhanced, laser desorption and ionization, time-of-flight mass
      spectrometry and Velos Orbitrap mass spectrometry. Several candidate biomarkers
      were further evaluated by Western blot and/or enzyme-linked immunosorbent assay
      (ELISA). Among the most promising was carbonic anhydrase 1 (CA1), a host protein
      found primarily in red blood cells and enterocytes that proved to be a negative
      biomarker for schistosomiasis in both mouse and human samples. Reduced serum CA-1
      levels were confirmed by both Western blot (murine and human: both P < 0.001) and
      ELISA (human: P < 0.01). Western blots of serial mouse sera revealed a
      progressive reduction in serum CA1 levels over the 12-week infection period. CA1
      is a promising negative serum biomarker for the diagnosis of S. mansoni
      infection.

PMID- 28500824
TI  - Vitamin D and aspects of female fertility.
AB  - The role of vitamin D in female reproduction has been intensively examined over
      the last few decades. A large body of evidence suggests that vitamin D might have
      beneficial effects on metabolic/hormonal parameters of PCOS and endometriosis,
      while it appears to be associated with IVF outcomes. However, due to the
      heterogeneity among observational and interventional studies, no cause-effect
      relationship has yet been established. The aim of this review is to analyze
      recent in vitro animal and human studies which examined the association of
      vitamin D with disease entities affecting female fertility potential. Recent
      research data strongly imply that vitamin D is implicated in female reproduction
      and might represent a beneficial and inexpensive therapeutic approach, in
      combination with first-line medical treatments, to female infertility.

PMID- 28500823
TI  - Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.
AB  - AbstractPregnant women and their developing fetuses are vulnerable to multiple
      environmental insults, including exposure to aflatoxin, a mycotoxin that may
      contaminate as much as 25% of the world food supply. We reviewed and integrated
      findings from studies of aflatoxin exposure during pregnancy and evaluated
      potential links to adverse pregnancy outcomes. We identified 27 studies (10 human
      cross-sectional studies and 17 animal studies) assessing the relationship between
      aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that
      aflatoxin exposure during pregnancy may impair fetal growth. Only one human study
      investigated aflatoxin exposure and prematurity, and no studies investigated its
      relationship with pregnancy loss, but animal studies suggest aflatoxin exposure
      may increase risk for prematurity and pregnancy loss. The fetus could be affected
      by maternal aflatoxin exposure through direct toxicity as well as indirect
      toxicity, via maternal systemic inflammation, impaired placental growth, or
      elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin
      could plausibly mediate maternal anemia, intrauterine growth restriction, fetal
      loss, and preterm birth. Given the widespread exposure to this toxin in
      developing countries, longitudinal studies in pregnant women are needed to
      provide stronger evidence for the role of aflatoxin in adverse pregnancy
      outcomes, and to explore biological mechanisms. Potential pathways for
      intervention to reduce aflatoxin exposure are urgently needed, and this might
      reduce the global burden of stillbirth, preterm birth, and low birthweight.

PMID- 28500825
TI  - Which type 2 diabetes mellitus patients should be screened for subclinical
      Cushing's syndrome?
AB  - OBJECTIVE: Diabetes or impaired glucose tolerance are common in patients with
      Cushing's syndrome (CS). In this study we investigated the incidence of
      subclinical Cushing's syndrome (SCS) in type 2 diabetic patients with poor and
      good metabolic control and the relationship between blood glucose and cortisol
      levels. DESIGN: A total of 400 type 2 diabetes mellitus (T2DM) patients (Group A,
      HbA1c >=8%, n=250; Group B, HbA1c <=6.5%, n=150) were included in the study.
      Biochemical tests followed by the 1 mg dexamethasone suppression test (DST) were
      performed. If post-DST cortisol levels were above 1.8 MUg/dl (non-suppressed
      group), the 2 mg DST test was performed for 2 days. Among the patients, post-DST
      cortisol of at least 1.8 MUg/dL and midnight serum cortisol levels of at least
      7.5 MUg/dL confirmed the diagnosis of CS. RESULTS: While SCS was observed in 5
      patients (2%) in Group A, no case was observed in group B. There was a
      statistically significant difference between groups for basal cortisol and post
      DST cortisol results (p<0.001 and p<0.001, respectively). Microvascular
      complication rates were higher in the non-suppressed group (p=0.007). Post-DST
      cortisol levels had a positive correlation with the number of complications and
      HbA1c levels (respectively r=0.213, p<0.001, and r=0.191, p<0.001). Multivariate
      regression analysis revealed that durations of DM, HbA1c level, and post 1 mg DST
      cortisol levels were associated with the number of complications. CONCLUSIONS:
      This study shows the presence of SCS in a notable number in T2DM patients having
      poor metabolic control. Screening with 1 mg and 2 mg DST of T2DM patients with
      poor metabolic control who are also obese and hypertensive and have microvascular
      complications may be an appropriate method for detection of SCS.

PMID- 28500826
TI  - Serum kisspeptin concentrations are negatively correlated with body mass index in
      adolescents with anorexia nervosa and amenorrhea.
AB  - OBJECTIVE: To measure, for the first time, serum kisspeptin concentrations in
      adolescent females with anorexia nervosa (AN) and associated amenorrhea, and
      investigate potential correlations of kisspeptin with anthropometric, bone and
      hormonal data. DESIGN: Setting: University Adolescent Medicine Center.
      PARTICIPANTS: Females aged 12-20 years with typical or atypical AN (based on DSM
      5 diagnostic criteria) and controls. INTERVENTIONS: Measurement of body mass
      index (BMI), whole body/lumbar spine bone mineral density and serum
      concentrations of kisspeptin, follicle stimulating hormone, luteinizing hormone
      (LH), prolactin (PRL), thyroid stimulating hormone (TSH), free thyroxine,
      triiodothyronine, estradiol (E2), 17-hydroxyprogesterone. MAIN OUTCOME MEASURES:
      Kisspeptin serum concentrations and correlations between kisspeptin and AN
      related anthropometric, bone and hormonal changes. RESULTS: Participants included
      37 females, 22 with AN (typical AN group=17, atypical AN group=5) and 15 in the
      control group. All typical AN patients had secondary amenorrhea. Wide inter
      subject variation (101.9-709.1 ng/L) in kisspeptin levels was observed with no
      significant differences among study groups; there was a trend toward higher
      concentrations in the atypical AN group. Adolescents with typical AN had
      significantly lower BMI (P<0.001), lumbar spine z-score (P=0.016), serum E2
      (P<0.001), LH (P=0.016), PRL (P=0.034) and TSH (P=0.045) than controls. They also
      had lower BMI (P=0.009) and TSH (P=0.027) than girls with atypical AN. An inverse
      correlation between BMI and serum kisspeptin was noted in the typical AN group
      (r=-0.60, P=0.012). CONCLUSIONS: Serum kisspeptin concentrations overlapped
      between patients and controls; in typical anorexic adolescents kisspeptin
      concentrations were negatively correlated with BMI. Future studies are needed to
      explore kisspeptin physiology in AN.

PMID- 28500827
TI  - Psychological vulnerability to stress in carriers of congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency.
AB  - OBJECTIVE: Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency (21-OHD) demonstrate increased secretion of cortisol precursors
      following ACTH stimulation, suggestive of impaired cortisol production and
      compensatory increases in hypothalamic corticotropin-releasing hormone (CRH)
      secretion. Both cortisol and CRH have behavioral effects, and hypothalamic CRH
      hypersecretion has been associated with chronic states of anxiety and depression.
      We performed an endocrinologic and psychological evaluation in carriers of 21-OHD
      and matched control subjects. DESIGN: We recruited 29 parents of children with
      classic CAH (14 males, 15 females; age (mean+/-SD): 41.8+/-5.7 yr), and hence 21
      OHD carriers, and 13 normal subjects (5 males, 8 females; age: 43.8+/-6.1 yr).
      All subjects underwent a formal ovine (o) CRH stimulation test with measurement
      of ACTH, cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione
      concentrations, which was preceded by determination of 24-hour urinary free
      cortisol (UFC) excretion. Psychometric assessment was performed by administering
      the State-Anxiety (STAI 1) and Trait-Anxiety (STAI 2) Inventory, Beck Depression
      Inventory, Symptom Checklist-90R and Temperament and Character Inventory.
      RESULTS: Carriers of 21-OHD had significantly higher 17-OHP concentrations
      following oCRH stimulation and higher STAI 1 (47.6+/-5.6 vs. 43.3+/-5.4, P=0.023)
      scores than control subjects. Mean 24-hour UFC concentrations were positively
      correlated with paranoid ideation (r=0.435; P=0.023) and psychoticism (r=0.454;
      P=0.017). Stepwise multiple linear regression analysis revealed that the single
      independent predictor of STAI 1 was peak stimulated 17-OHP concentrations (beta:
      0.055, SE: 0.023, R2: 0.290, P=0.031). CONCLUSIONS: Carriers of 21-OHD may be
      predisposed to the development of anxiety disorders.

PMID- 28500828
TI  - The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in
      postmenopausal women.
AB  - OBJECTIVE: Skeletal development, linear growth, cartilage biology and bone
      turnover are highly dependent on the activity of thyroid hormones. Thyroid
      dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as
      a chronic inflammatory condition, may be an important contributing factor to
      impaired bone quality in these patients. MATERIALS AND METHODS: Measurement of
      TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were
      performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed
      with subclinical hypothyroidism) divided into subgroups according to the presence
      of TPOAb. RESULTS: In multivariate logistic regression analysis only TPOAb were
      found to be significantly related to fracture, independently of TSH values
      (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX
      score for hip and for major osteoporotic fractures were associated with the
      presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic
      regression model, as well as in a model adjusted for age, BMI and smoking. TSH
      was a better predictive factor for fractures in women with subclinical
      hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p
      <0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is
      associated with decreased bone mineral density at both spine and hip and risk of
      future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is
      a potential marker of higher fracture risk in these patients. However, in
      subclinical hypothyroidism, TSH is a better indicator of future fragility
      fractures than TPOAb.

PMID- 28500829
TI  - Removal of a high-fat diet, but not voluntary exercise, reverses obesity and
      diabetic-like symptoms in male C57BL/6J mice.
AB  - OBJECTIVE: Both the consumption of high-fat diets and exercise are known to
      produce alterations in metabolism and behavior. This study focuses on the effects
      of a change to a low-fat diet from a high-fat diet and voluntary exercise on
      obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J
      mice. DESIGN: Mice were initially given either a high-fat diet or regular chow,
      along with a cage with a running-wheel to mimic exercise, or one without, to
      determine to what extend exercise affects these symptoms. Then half of the mice
      given a high-fat diet were switched to regular chow to ascertain if the switch in
      diet would improve type-2 diabetic-like and obesity symptoms. RESULTS: Wheel
      running alone produced an improvement in insulin in mice continuously fed a high
      fat diet (p=0.006), but running-wheels did not produce any further improvements
      in mice with regular chow replacement (p=0.999) or in controls (p=0.996).
      Replacement of a high-fat diet with regular chow led to physiological
      improvements in insulin (p=0.012) and leptin (p <0.001), glucose tolerance (p
      <0.001), and obesity (p <0.001), more so than exercise alone. Mice consuming a
      high-fat diet without a wheel exhibited reduced home-cage activity compared to
      controls after the diet switch (p=0.030), while no reduction was found in running
      wheel activity between high-fat diet and regular chow consuming mice after
      switching diets (p=0.516). CONCLUSIONS: These results suggest that exercise is
      only partially beneficial to improving health outcomes in mice consuming a high
      fat diet, whereas incorporating a better diet, even without exercise, improves
      quality of health and can suppress T2DM symptoms and related conditions more so
      than exercise alone.

PMID- 28500830
TI  - Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti
      TPO levels in Iranian patients with subclinical hypothyroidism.
AB  - OBJECTIVE: Subclinical hypothyroidism (SCH) is defined as high levels of TSH in
      the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays
      a key role in thyroid hormone synthesis, variations in the TPO gene can change
      the enzyme structure and result in the production of anti-TPO antibodies. The aim
      of this study was to examine the relationship between the Asn698Thr (A2095C) and
      Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients
      with SCH. DESIGN: In this study, 150 individuals (75 cases and 75 controls), aged
      19-75 years, were selected randomly by a clinician. The thyroid function tests
      included were FT3, FT4, TSH and anti-TPO antibodies using ELISA. The TPO gene
      polymorphisms were examined by PCR-RFLP. RESULTS: Anti-TPO levels in the
      experimental group was significantly increased (P=0.020). The A2095C genotype
      frequency in the experimental and control groups were 37.3% vs 34.7% for the AA
      healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively
      (P=0.001). The A2173C genotype frequency in the experimental and control groups
      were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC,
      respectively (P <0.001). The increased anti-TPO antibodies were significantly
      associated with the A2173C polymorphism (P=0.035). The findings showed that the
      chance (odds ratio) of developing subclinical hypothyroidism in individuals who
      had C alleles was 1.5 and 5.6-fold higher than in individuals without these
      alleles in the A2095C and A2173C regions, respectively. CONCLUSIONS:
      Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in
      patients with SCH can be helpful for prediction of overt hypothyroidism.

PMID- 28500831
TI  - Somatotropinomas inadequately controlled with octreotide may over-respond to
      pasireotide: the importance of dose adjustment to achieve long-term biochemical
      control.
AB  - OBJECTIVE: To present two female patients with acromegaly inadequately controlled
      with long-acting octreotide who were subsequently treated with the multireceptor
      targeted somatostatin analogue pasireotide that over-suppressed IGF-1 levels.
      METHODS: We report two patients who failed surgery and received long-acting
      octreotide 20-30 mg/month as part of two double-blind, Phase III clinical trials.
      After 6-12 months of octreotide treatment, both patients remained inadequately
      controlled and were switched to long-acting pasireotide 40 mg/month as part of a
      crossover extension phase. RESULTS: During the core phase of the studies the
      patients received octreotide 20-30 mg/month, but GH and IGF-1 levels remained
      above normal. They were switched to pasireotide 40 mg/month after 6 and 12
      months, according to the study protocols. After crossover, GH and IGF-1 decreased
      and normalized, but continued treatment led to further reduction of IGF-1 to
      below the normal; these reduced levels mildly increased following pasireotide
      dose reduction to 20 mg/month. Tumour volume was reduced and the clinical signs
      and symptoms of acromegaly also improved. CONCLUSION: These patients achieved
      long-term biochemical control, tumour volume reduction and improvement of
      clinical signs/symptoms after switching from octreotide to pasireotide. IGF-1
      over-suppression is observed in a few patients and requires dose adjustment of
      pasireotide.

PMID- 28500832
TI  - Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft
      cyst.
AB  - BACKGROUND: Tetrasomy X is a rare chromosomal aneuploidy seen in girls,
      associated with facial dysmorphism, premature ovarian insufficiency and
      intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's
      pouch which may cause multiple pituitary hormone deficiencies by exerting
      pressure on the pituitary gland in the sella. METHODS/RESULTS: The patient was
      diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple
      endocrine stimulation tests revealed RCC and combined pituitary hormone
      deficiency (growth hormone deficiency, secondary adrenal insufficiency and
      central hypothyroidism) likely due to RCC. CONCLUSION: We report the first case
      in the literature of a girl with 48, XXXX and combined pituitary hormone
      deficiency due to Rathke's cyst.

PMID- 28500833
TI  - The male bride: a story of Sexual Female-to-Male Transformation at marriage from
      the Hellenistic period, recorded by Phlegon of Tralles.

PMID- 28500834
TI  - Hermaphroditism: an obsolete diagnosis?

PMID- 28500835
TI  - Hypophysis. From outgrowth, to ocular disorder to pituitary gland.

PMID- 28500856
TI  - Effect of low-level laser therapy on tissue repair after dental extraction in
      rats administered zoledronic acid and dexamethasone.
AB  - Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic
      and oncological pathologies involving the skeletal system. Because of the
      severity of the BP associated osteonecrosis of the jaws, the difficulties of
      treatment, and patient discomfort, additional support methods for their
      management are needed. Laser therapy has an easy handling, photobiostimulator
      effect on tissues healing, so it can be considered a preferred therapy. The aim
      of this study was to evaluate the influence of low-level laser therapy in the 685
      and 830-nm wavelength in the healing process of the bone and soft tissues in
      rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that
      underwent a surgery for the extraction of upper molars. There were statistically
      significant differences in the clinical evaluation of the wound and the weight of
      the animals. Regarding the histological evaluation, it was possible to observe
      the different maturations of the healing stage between groups. The effect of drug
      therapy with ZA and dexamethasone in the bone tissue repair process induces
      osteonecrosis of the jaw in rats and slows down the healing process. In the laser
      groups, at the stipulated dosimetry, a positive influence on the bone and soft
      tissue repair process was observed.

PMID- 28500855
TI  - The Evolutionary Theory of Depression.
AB  - The evolutionary success of Homo sapiens is attributed to the following two
      factors: the upright body posture (which freed our hands and allowed
      unconstrained operation of various objects) and intensive development of the
      frontal lobes, mainly the Broca area of the brain. Underlining the uniqueness of
      the human brain, we often forget about the fact that the frontal lobes - the most
      developed part of the brain - are at the same time our greatest weakness, exposed
      to the action of damaging factors in our evolving environment. Is depression the
      cost of evolution?

PMID- 28500858
TI  - The Coumarin-Dimer Spring-The Struggle between Charge Transfer and Steric
      Interactions.
AB  - The synthesis of a weakly coupled, strongly polarized coumarin dimer has been
      achieved for the first time. The three-step strategy comprises the Skattebol
      formylation followed by the Knoevenagel reaction and the formation of a tertiary
      amide by using a peptide-type procedure. The molecule consists of two different
      coumarin moieties: One is a classical donor-acceptor system and the second one
      possesses a weaker amide donor at the 7-position. The polarized coumarin dimer
      can form an electronically conjugated structure possessing an electric dipole
      larger than that of 7-(dimethylamino)coumarin-3-carboxylic acid. The limited
      flexibility of the inter-coumarin connection results in stable conformers of
      different electric dipole moments and complex photophysics. In the solid state,
      this compound has a strongly bent conformation with the two coumarin units
      forming an angle of around 74 degrees . In solution, two conformers are in
      equilibrium. The existence of the molecule as two conformers in the ground state
      has been confirmed by optical studies, and further corroborated by molecular
      calculations. The fluorescence spectra possess a unique feature: A charge
      transfer band (ca. 550 nm) is visible only in nonpolar or weakly polar solvents.
      Optical spectroscopy studies coupled with molecular calculations allowed us to
      rationalize this phenomenon: The large amplitude of intramolecular motions is
      responsible for the conformational isomerization as well as producing a conical
      intersection between the potential energy surfaces of the excited singlet state
      and the ground state, which opens an internal conversion channel that effectively
      competes with the fluorescence of the conformers.

PMID- 28500857
TI  - Polydimethylsiloxane-based optical waveguides for tetherless powering of floating
      microstimulators.
AB  - Neural electrodes and associated electronics are powered either through
      percutaneous wires or transcutaneous powering schemes with energy harvesting
      devices implanted underneath the skin. For electrodes implanted in the spinal
      cord and the brain stem that experience large displacements, wireless powering
      may be an option to eliminate device failure by the breakage of wires and the
      tethering of forces on the electrodes. We tested the feasibility of using
      optically clear polydimethylsiloxane (PDMS) as a waveguide to collect the light
      in a subcutaneous location and deliver to deeper regions inside the body, thereby
      replacing brittle metal wires tethered to the electrodes with PDMS-based optical
      waveguides that can transmit energy without being attached to the targeted
      electrode. We determined the attenuation of light along the PDMS waveguides as
      0.36 +/- 0.03 ?? dB / cm and the transcutaneous light collection efficiency of
      cylindrical waveguides as 44 % +/- 11 % by transmitting a laser beam through the
      thenar skin of human hands. We then implanted the waveguides in rats for a month
      to demonstrate the feasibility of optical transmission. The collection efficiency
      and longitudinal attenuation values reported here can help others design their
      own waveguides and make estimations of the waveguide cross-sectional area
      required to deliver sufficient power to a certain depth in tissue.

PMID- 28500859
TI  - Proteins with Site-Specific Lysine Methylation.
AB  - As an important epigenetic mark, lysine methylations play critical roles in the
      regulation of both chromatin and non-chromatin proteins. There are three levels
      of lysine methylation, mono-, di-, and trimethylation. Each one has turned out to
      be biologically distinctive. For the biochemical characterization of proteins
      with lysine methylation, multiple chemical biology methods have been developed.
      This concept article will highlight these developments and their applications in
      epigenetic investigation of protein functions.

PMID- 28500861
TI  - Overview of high-risk medical device recalls in obstetrics and gynecology from
      2002 through 2016: implications for device safety.
AB  - The field of women's health has endured numerous recent controversies involving
      medical devices such as pelvic meshes, laparoscopic morcellators, and a
      hysteroscopic sterilization device. With the recent passage of the 21st Century
      Cures Act, new legislation will change how the Food and Drug Administration
      regulates medical devices. Given these controversies and new changes, we
      investigated high-risk, class I recalls in women's health from 2002 through 2016.
      Class I recalls for medical devices are defined by the Food and Drug
      Administration as the most serious recall events and are designated for
      situations when there is a reasonable probability of serious adverse health
      consequences or death. We defined a recall event as a group of unique Food and
      Drug Administration recalls that share a similar reason for recall and occurred
      within a 1-month time frame. In total, 7 class I recall events were identified
      encompassing 83 unique recalls affecting >88,000 medical devices in distribution.
      Recalls involved a broad range of devices used in women's health including
      diagnostic assays for chlamydia and gonorrhea, a laparoscopic tissue morcellator,
      and obstetrical/gynecological surgical kits. Four of 7 (57%) recall events were
      due to postmarketing problems such as improper packaging and labeling while the
      remaining 3 (43%) recalls were due to premarketing problems (eg, software
      issues). Additionally, 3 of 7 (43%) recall events were cleared via the 510(k)
      pathway, while the remaining were essentially exempt from any form of premarket
      approval. Two recall events involved sterility concerns of 71 surgical kits used
      in obstetrics and gynecological surgeries representing the majority of affected
      devices (78,423) in distribution. Class I medical device recalls are rare but
      serious events. Most recalled devices in women's health had minimal preapproval
      regulation and were recalled due to both premarketing and postmarketing reasons.
      Future regulatory efforts to improve postmarketing surveillance may mitigate the
      potential impact and frequency of class I recalls, but do not replace the need
      for a higher burden of proof for both safety and efficacy prior to medical device
      approval.

PMID- 28500860
TI  - Interventions for preventing silent cerebral infarcts in people with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic
      disorders in the world, due to the inheritance of two abnormal haemoglobin (beta
      globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary
      complications, and premature death. Silent cerebral infarcts are the commonest
      neurological complication in children and probably adults with SCD. Silent
      cerebral infarcts also affect academic performance, increase cognitive deficits
      and may lower intelligence quotient. OBJECTIVES: To assess the effectiveness of
      interventions to reduce or prevent silent cerebral infarcts in people with SCD.
      SEARCH METHODS: We searched for relevant trials in the Cochrane Library, MEDLINE
      (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980),
      and ongoing trial databases; all searches current to 19 September 2016. We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials
      Register: 06 October 2016. SELECTION CRITERIA: Randomised controlled trials
      comparing interventions to prevent silent cerebral infarcts in people with SCD.
      There were no restrictions by outcomes examined, language or publication status.
      DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological
      procedures. MAIN RESULTS: We included five trials (660 children or adolescents)
      published between 1998 and 2016. Four of the five trials were terminated early.
      The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One
      trial focused on preventing silent cerebral infarcts or stroke; three trials were
      for primary stroke prevention and one trial dealt with secondary stroke
      prevention.Three trials compared the use of regular long-term red blood cell
      transfusions to standard care. Two of these trials included children with no
      previous long-term transfusions: one in children with normal transcranial doppler
      (TCD) velocities; and one in children with abnormal TCD velocities. The third
      trial included children and adolescents on long-term transfusion.Two trials
      compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron
      chelation therapy: one in primary prevention (children), and one in secondary
      prevention (children and adolescents).The quality of the evidence was moderate to
      very low across different outcomes according to GRADE methodology. This was due
      to trials being at high risk of bias because they were unblinded; indirectness
      (available evidence was only for children with HbSS); and imprecise outcome
      estimates. Long-term red blood cell transfusions versus standard care Children
      with no previous long-term transfusions and higher risk of stroke (abnormal TCD
      velocities or previous history of silent cerebral infarcts) Long-term red blood
      cell transfusions may reduce the incidence of silent cerebral infarcts in
      children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence
      interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence);
      but make little or no difference to the incidence of silent cerebral infarcts in
      children with previous silent cerebral infarcts on magnetic resonance imaging and
      normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196
      participants, low-quality evidence).No deaths were reported in either trial.Long
      term red blood cell transfusions may reduce the incidence of: acute chest
      syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low
      quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials,
      326 participants, low-quality evidence); and probably reduces the incidence of
      clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants,
      moderate-quality evidence).Long-term red blood cell transfusions may improve
      quality of life in children with previous silent cerebral infarcts (difference
      estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166
      participants), but may have no effect on cognitive function (least squares means:
      1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence).
      Transfusions continued versus transfusions halted: children and adolescents with
      normalised TCD velocities (79 participants; one trial)Continuing red blood cell
      transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95%
      CI 0.09 to 0.97 (low-quality evidence).We are very uncertain whether continuing
      red blood cell transfusions has any effect on all-cause mortality, Peto odds
      ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01
      to 4.35) (very low-quality evidence).The trial did not report: comparative
      numbers for SCD-related adverse events; quality of life; or cognitive function.
      Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention,
      children (121 participants; one trial)We are very uncertain whether switching to
      hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no
      infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD
      related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence).
      Secondary prevention, children and adolescents with a history of stroke (133
      participants; one trial)We are very uncertain whether switching to hydroxyurea
      and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI
      0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95%CI 0.06 to 16.41); or
      clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality
      evidence).Switching to hydroxyurea and phlebotomy may increase the risk of SCD
      related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality
      evidence).Neither trial reported on quality of life or cognitive function.
      AUTHORS' CONCLUSIONS: We identified no trials for preventing silent cerebral
      infarcts in adults, or in children who do not have HbSS SCD.Long-term red blood
      cell transfusions may reduce the incidence of silent cerebral infarcts in
      children with abnormal TCD velocities, but may have little or no effect on
      children with normal TCD velocities. In children who are at higher risk of stroke
      and have not had previous long-term transfusions, long-term red blood cell
      transfusions probably reduce the risk of stroke, and other SCD-related
      complications (acute chest syndrome and painful crises).In children and
      adolescents at high risk of stroke whose TCD velocities have normalised,
      continuing red blood cell transfusions may reduce the risk of silent cerebral
      infarcts. No treatment duration threshold has been established for stopping
      transfusions.Switching to hydroxyurea with phlebotomy may increase the risk of
      silent cerebral infarcts and SCD-related serious adverse events in secondary
      stroke prevention.All other evidence in this review is of very low-quality.

PMID- 28500862
TI  - Enhanced Tau Aggregation in the Presence of Amyloid beta.
AB  - Amyloid plaques and neurofibrillary tangles co-occur in Alzheimer disease, but
      with different topological and temporal patterns. Whether these two lesions are
      independent or pathobiologically related is uncertain. For example, amyloid
      deposition in the neocortex precedes the spread of tau neurofibrillary tangles
      from the limbic areas to the cortex. We examined the aggregation properties of
      tau isolated from human cases with early tau pathology (Braak II) with and
      without plaques. Using a well-established HEK cell biosensor assay, we show that
      tau from cases with plaques has an enhanced ability to induce tau aggregates
      compared to tau from cases without plaques. To further explore this effect, we
      combined mice carrying the APP/PS1 transgene array that develop plaques with
      rTg4510 mice carrying the P301L mutant human tau transgene that develop extensive
      tau pathology with age. The resulting APP/PS1-rTg4510 mice had a threefold
      increase in tau seeding activity over the rTg4510 strain, without change in tau
      production or extracellular release. Surprisingly, this effect was observed
      before overt amyloid deposition. The enhancement of tau aggregation was also
      apparent by an increase in histological measures of tau pathology in young
      APP/PS1-rTg4510 mice and an increase in high-molecular-weight tau. Overall, these
      data provide evidence that amyloid beta acts to enhance tau pathology by
      increasing the formation of tau species capable of seeding new aggregates.

PMID- 28500863
TI  - Lymphoepithelioma-Like Carcinoma in Liver.
AB  - Liver cancer, primarily encompassing hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma, has become the second leading cause of worldwide cancer
      related death during the past two decades. Lymphoepithelioma-like carcinomas
      (LELCs) are defined as tumors composed of undifferentiated epithelial cells with
      a prominent lymphoid infiltrate, and can arise in the liver as hepatocellular or
      cholangiocarcinoma forms. Patients with liver LELC display distinctive
      demographics and tumor characteristics. LELCs also appear to be associated with
      strikingly better outcomes compared to typical liver cancers, with 5-year
      survival rates of 57% to 100% versus 12% to 68%, respectively. Liver LELCs
      represent a unique model of immune response in liver cancer. Data on LELCs of the
      liver remain limited, and future comprehensive studies are needed to further
      elucidate this disease, which could ultimately offer precious insights for
      immunotherapeutic strategies in liver cancer.

PMID- 28500864
TI  - Identification of Human Bocavirus type 4 in a child asymptomatic for respiratory
      tract infection and acute gastroenteritis - Goiania, Goias, Brazil.
AB  - Human Bocavirus (HBoV) has been identified from feces and respiratory samples
      from cases of both acute gastroenteritis and respiratory illness as well as in
      asymptomatic individuals. The aim of this study was to detect and characterize
      HBoV from fecal samples collected from hospitalized children aged less than five
      years old with no symptoms of respiratory tract infection (RTI) or acute
      gastroenteritis (AGE). The study involved 119 children and one fecal sample was
      collected from each participant between 2014 and 2015. HBoV was detected using
      Nested-PCR, and the viral type identified by genomic sequencing. HBoV-4 was
      identified from one sample obtained from a hospitalized child with soft tissue
      tumor of the submandibular region. This is the first report of HBoV-4
      identification in Brazil, but we consider that this type may be circulating in
      the country similar to the other types and new investigations are necessary.

PMID- 28500865
TI  - Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.
AB  - BACKGROUND AND AIMS: Dihydromyricetin, the most abundant flavonoid in Ampelopsis
      grossedentata, exerts numerous pharmacological activities, including anti
      inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities;
      however, its protective effect against atherosclerosis remains poorly understood.
      The aim of the present study was to evaluate the effects of dihydromyricetin on
      high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr-/
      ) mice. METHODS: Blood samples were collected for determination of serum lipid
      profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology,
      hepatic lipid content, quantification of atherosclerosis, assessment of oxidative
      stress and inflammation were performed on liver and aorta samples by molecular
      biology methods. The effects of dihydromyricetin on ox-LDL-induced human
      umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation
      were further studied. RESULTS: (1) Dihydromyricetin ameliorated hyperlipidemia,
      reduced serum ox-LDL, IL-6 and TNF-alpha levels in HFD-fed LDLr-/- mice.
      Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and
      increased protein expressions of PPARalpha, LXRalpha and ABCA1. (3) It inhibited
      atherosclerotic lesion formation and favoured features of plaque stability. (4)
      Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the
      reduced IL-6 and TNF-alpha mRNA expression; (5) it prevented hepatic and aortic
      oxidative stress by normalizing activities of antioxidant enzymes in the liver
      and suppressing reactive oxygen species generation and NOX2 protein expression in
      both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion
      and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation
      and enhanced cholesterol efflux. CONCLUSIONS: These findings suggest that
      dihydromyricetin could reduce atherosclerosis via its pleiotropic effects,
      including improvement of endothelial dysfunction, inhibition of macrophage foam
      cell formation, amelioration of lipid profiles, anti-inflammatory action and anti
      oxidative effect.

PMID- 28500866
TI  - Presence of eating disorders and its relationship to anxiety and depression in
      pregnant women.
AB  - BACKGROUND: women who have inadequate nutrient intake are more likely to develop
      a risky pregnancy. The purpose of this study was to determine the presence of
      eating disorders and its association with anxiety and depression symptomatology
      in high-risk pregnancies. METHODS: this is a cross-sectional and prospective
      study conducted at the tertiary university hospital in the city of Sao Paulo,
      Brazil. 913 pregnant women waiting for the Obstetrics' outpatient appointment
      were invited to participate in the study on their 2nd and 3rd trimester of
      pregnancy. Structured interviews were carried out and the Structured Clinical
      Interview for DSM Disorders and Hospital Anxiety and Depression Scale were
      applied. FINDINGS: prevalence of eating disorder (ED) during pregnancy was 7.6%
      (n=69) (95% CI: 5.84% -9.28%), 0.1% (n=1) for anorexia nervosa; 0.7% (n=6) for
      bulimia nervosa; 1.1% (n=10) for binge eating disorder, and 5.7% (n=52) for pica.
      A statistically significant difference was found between the anxiety (p<0.01) and
      depressive symptoms (p<0.01). CONCLUSIONS: the prevalence of ED (7.6%) and its
      association with anxiety and depression symptoms during pregnancy highlights the
      need for specialist care for prevention, diagnosis and treatment. Given the
      importance of proper nutrition during pregnancy, both with regard to maternal
      health and fetal development, it is necessary to have specific predetermined
      evaluation protocols implemented by health care professionals for the diagnosis
      of ED during pregnancy.

PMID- 28500867
TI  - Hospitalization for Charcot neuroarthropathy in diabetes: A population study in
      Italy.
AB  - AIMS: To provide data on hospitalization and incidence rates of Charcot
      neuroarthropathy (CN) and its relation to lower limbs'
      amputations/revascularizations in population with diabetes of Italy as well as of
      one of its regions (Tuscany). METHODS: Hospitalizations with CN diagnosis (codes
      ICD-9-CM: 7130, 7135, 7138) have been recorded in people with diabetes over years
      2003-2013 in Italy and 2008-2015 in Tuscany. Amputations, peripheral vascular
      disease, revascularizations and infections were likewise evaluated. RESULTS:
      Between 2003 and 2013 CN hospitalizations were very infrequent in Italy ranging
      between 14*100,000 and 11*100,000 patients with diabetes. In Tuscany they
      declined to a minimum of 7*100,000 patients in 2015, after a previous increase to
      a maximum of 22*100,000 (p=NS for both). Yearly CN incidence remained constant in
      Italy, declining in Tuscany to a minimum of 3.4*100,000 diabetic patients in 2015
      (p=0.047). CN patients were younger and with longer length of hospital stay than
      those with non-Charcot diabetic foot (p<0.05 for both). Amputation and infection
      rates were manifold higher in CN patients than in those with non-Charcot diabetic
      foot, while the revascularization rate was similar in both. CONCLUSIONS: Over
      last decade, in Italy and Tuscany yearly CN incidence and hospitalization rates
      concerned only a small percentage of patients, remaining constant over years and
      declining in Tuscany in the last couple of years. CN was significantly associated
      to younger age, longer hospital stay and greater risk of amputations and
      infections while the need of revascularization was similar to that of non-Charcot
      diabetic foot.

PMID- 28500868
TI  - Type 1 diabetes mellitus care and education in China: The 3C study of coverage,
      cost, and care in Beijing and Shantou.
AB  - AIMS: The paucity of data on Type 1 diabetes in China hinders progress in care
      and policy-making. This study compares Type 1 diabetes care and clinical outcomes
      in Beijing and Shantou with current clinical guidelines. METHODS: The 3C Study
      was a cross-sectional study of the clinical practices and outcomes of people with
      Type 1 diabetes. The study sequentially enrolled 849 participants from hospital
      records, inpatient wards, and outpatient clinics. Data were collected via face-to
      face interviews with patients and health professionals, the Summary of Diabetes
      Self-Care Activities, medical records, and venous blood samples. Care was audited
      using ISPAD/IDF indicators. Data underwent descriptive analysis and tests for
      association. RESULTS: The median age was 22years (IQR=13-34years), and 48.4% of
      the sample had diabetes less than six years. The median HbA1c was 8.5%
      (69mmol/mol) (IQR 7.2-10.5%), with significant regional variance (p=0.002).
      Insulin treatment was predominantly two injections/day (45% of patients). The
      highest incidence of diabetic ketoacidosis was 14.4 events/100 patient years
      among adolescents. Of the 57.3% of patients with LDL-C>2.6mmol/L, only 11.2%
      received treatment. Of the 10.6% considered hypertensive, 47.1% received
      treatment. Rates of documented screening for retinopathy, nephropathy, and
      peripheral neuropathy were 35.2%, 42.3%, and 25.0%, respectively. The median
      number of days of self-monitoring/week was 3.0 (IQR=1.0-7.0). There were
      significant differences in care practices across regions. CONCLUSIONS: The study
      documented an overall deficit in care with significant regional differences noted
      compared to practice guidelines. Modifications to treatment modalities and the
      structure of care may improve outcomes.

PMID- 28500869
TI  - To sleep or not to sleep: neuronal and ecological insights.
AB  - Daily, animals need to decide when to stop engaging in cognitive processes and
      behavioral responses to the environment, and go to sleep. The main processes
      regulating the daily organization of sleep and wakefulness are circadian rhythms
      and homeostatic sleep pressure. In addition, motivational processes such as food
      seeking and predator evasion can modulate sleep/wake behaviors. Here, we discuss
      the principal processes regulating the propensity to stay awake or go to sleep
      focusing on neuronal and behavioral aspects. We first introduce the neuronal
      populations involved in sleep/wake regulation. Next, we describe the circadian
      and homeostatic drives for sleep. Then, we highlight studies demonstrating
      various effects of motivational processes on sleep/wake behaviors, and discuss
      possible neuronal mechanisms underlying their control.

PMID- 28500871
TI  - The ability to tickle oneself is associated with level of psychometric schizotypy
      in non-clinical individuals.
AB  - A recent study (Lemaitre et al., 2016, Consciousness and Cognition, 41, 64-71)
      found that non-clinical individuals who scored highly on a psychometric scale of
      schizotypy were able to tickle themselves. The present study aimed to extend this
      finding by investigating whether the ability to tickle oneself was associated
      with level of psychometric schizotypy considered as a continuous variable. One
      hundred and eleven students completed the Schizotypal Personality Questionnaire
      (SPQ). A mechanical device delivered tactile stimulation to participants' palms.
      The device was operated by the experimenter (External) or the participant (Self).
      Participants were asked to rate the intensity, ticklishness and pleasantness of
      the stimulation. A significant association was observed between participants'
      tactile self-suppression (External minus Self) and their score on the SPQ. These
      results suggest that the ability to suppress the tactile consequences of self
      generated movements varies across the general population, and maps directly onto
      the personality dimension of schizotypy.

PMID- 28500870
TI  - Brainstem regulation of slow-wave-sleep.
AB  - Recent work has helped reconcile puzzling results from brainstem transection
      studies first performed over 60 years ago, which suggested the existence of a
      sleep-promoting system in the medullary brainstem. It was specifically shown that
      GABAergic neurons located in the medullary brainstem parafacial zone (PZGABA) are
      not only necessary for normal slow-wave-sleep (SWS) but that their selective
      activation is sufficient to induce SWS in behaving animals. In this review we
      discuss early experimental findings that inspired the hypothesis that the caudal
      brainstem contained SWS-promoting circuitry. We then describe the discovery of
      the SWS-promoting PZGABA and discuss future experimental priorities.

PMID- 28500873
TI  - Evaluation methods for assessing effectiveness of in situ remediation of soil and
      sediment contaminated with organic pollutants and heavy metals.
AB  - Soil and sediment contamination has become a critical issue worldwide due to its
      great harm to the ecological environment and public health. In recent years, many
      remediation technologies including physical, chemical, biological, and combined
      methods have been proposed and adopted for the purpose of solving the problems of
      soil and sediment contamination. However, current research on evaluation methods
      for assessing these remediation technologies is scattered and lacks valid and
      integrated evaluation methods for assessing the remediation effectiveness. This
      paper provides a comprehensive review with an environmental perspective on the
      evaluation methods for assessing the effectiveness of in situ remediation of soil
      and sediment contaminated with organic pollutants and heavy metals. The review
      systematically summarizes recent exploration and attempts of the remediation
      effectiveness assessment based on the content of pollutants, soil and sediment
      characteristics, and ecological risks. Moreover, limitations and future research
      needs of the practical assessment are discussed. These limitations are not
      conducive to the implementation of the abatement and control programs for soil
      and sediment contamination. Therefore, more attention should be paid to the
      evaluation methods for assessing the remediation effectiveness while developing
      new in situ remediation technologies in future research.

PMID- 28500874
TI  - Effects of Intermittent Low-Dose Parathyroid Hormone Treatment on Rapid
      Mandibular Distraction Osteogenesis in Rabbits.
AB  - PURPOSE: To determine whether low-dose recombinant human parathyroid hormone
      (rhPTH) would have a beneficial effect on regenerate healing and surrounding bone
      in a rabbit model of rapid mandibular distraction osteogenesis (DO). MATERIALS
      AND METHODS: Twenty-eight rabbits underwent unilateral mandibular lengthening at
      a rapid rate of 2 mm per day for 5 days. From the first day of DO, the
      experimental group received daily subcutaneous injections of rhPTH 10 MUg/kg for
      30 days and the control group received the same volume of saline (n = 14 in each
      group). At 6 weeks after completion of DO, the distracted callus was examined by
      micro-computed tomography (micro-CT), histology, and the 3-point bending test.
      Moreover, bone mineral density of the anterior pin region was evaluated by dual
      energy x-ray absorptiometry. RESULTS: Under rapid distraction, poor bone healing
      was observed in the distracted callus from the control group. In contrast, more
      mature and abundant bone formation was found in the distracted callus from the
      experimental group by histologic and micro-CT examinations. Quantitatively, the
      PTH-treated animals had superior parameters in bone volume fraction, trabecular
      number, and trabecular thickness and mechanical properties compared with controls
      (P < .05). Bone mineral density of the anterior pin region was greater in the
      experimental than in the control group (P < .05). CONCLUSION: Low-dose
      intermittent rhPTH administration not only enhances new bone formation but also
      can prevent fixator-related osteoporosis of surrounding segments after rapid
      mandibular DO in rabbits.

PMID- 28500872
TI  - CYP3A genes and the association between prenatal methylmercury exposure and
      neurodevelopment.
AB  - BACKGROUND: Results on the association between prenatal exposure to methylmercury
      (MeHg) and child neuropsychological development are heterogeneous. Underlying
      genetic differences across study populations could contribute to this varied
      response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A
      (CYP3A) family as candidate MeHg susceptibility genes. OBJECTIVES: We evaluated
      whether genetic variation in CYP3A genes influences the association between
      prenatal exposure to MeHg and child neuropsychological development. METHODS: The
      study population included 2639 children from three birth cohort studies: two
      subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during
      the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age,
      2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of
      age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal
      hair and/or cord blood samples. Neuropsychological development was evaluated
      using Bayley Scales of Infant Development (BSID). Three functional polymorphisms
      in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and
      rs2740574 (CYP3A4). RESULTS: There was no association between CYP3A polymorphisms
      and cord mercury concentrations. The scores for the BSID mental scale improved
      with increasing cord blood mercury concentrations for carriers of the most active
      alleles (beta[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98]
      for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This
      association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes.
      The interaction between the CYP3A genes and total mercury was significant
      (p<0.05) in European cohorts only. CONCLUSIONS: Our results suggest that the
      polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure
      during early life development.

PMID- 28500875
TI  - Upper Airway Changes After Mandibular Setback and/or Advancement Genioplasty in
      Obese Patients.
AB  - PURPOSE: Orthognathic surgeries, such as bilateral sagittal split ramus osteotomy
      (BSSO) and genioplasty, can influence the pharyngeal airway space (PAS) and this
      has been supported by previous studies. The purpose of this study was to assess
      changes of the PAS in patients with a high body mass index (BMI) likely to have
      narrow airways before and after setback BSSO with or without advancement
      genioplasty surgery by 3-dimensional computed tomography. MATERIALS AND METHODS:
      Thirty-five adults with a BMI of at least 24.0 kg/m2 were treated from 2010 to
      2016. Samples were grouped mandibular setback (group A; n = 11), advancement
      genioplasty (group B; n = 12), and mandibular setback plus advancement
      genioplasty (group C; n = 12). Computed tomograms were obtained 1 week
      preoperatively (T0), 1 week postoperatively (T1), and at least 1 year
      postoperatively (T2). The area of the posterior nasal spine and posterior plane
      (PPA), the soft palate plane (SPA), the plane of the most posterior point of the
      tongue base (PTA), the plane of the root of the epiglottis (EA), and the volumes
      of the palatopharyngeal part (VP), oropharyngeal part (VO), glossopharyngeal part
      (VG), and laryngeal part (VL) were measured and compared within groups using
      analysis of variance. The P value was set at .05. RESULTS: In group A, all
      results showed statistically significant differences (P < .05) from T0 to T2
      except for VO, VG, VL, SPA, PTA, and EA. In group B, VO, VG, VL, SPA, PTA, and EA
      showed statistically significant increases (P < .05) from T0 to T2. The hyoid at
      T2 showed significant advancement compared with T0 (P < .05). In group C, there
      were statistically significant decreases (P < .05) from T0 to T1 for VG, VL, PTA,
      and EA. CONCLUSION: In adults with a high BMI, mandibular setback BSSO could
      decrease the PAS, whereas advancement genioplasty could enlarge the PAS, after
      surgery. Therefore, undergoing advancement genioplasty concurrently with
      mandibular setback BSSO could help in lessening the negative effects of a PAS
      decrease.

PMID- 28500876
TI  - Does Adjunctive Botulinum Toxin A Reduce Pain Scores When Combined With
      Temporomandibular Joint Arthroscopy for the Treatment of Concomitant
      Temporomandibular Joint Arthralgia and Myofascial Pain?
AB  - PURPOSE: Currently, there is no standard of care for the treatment of refractory
      myofascial pain and concomitant temporomandibular joint (TMJ) arthralgia. This
      comparative study was conducted to determine the effectiveness of botulinum toxin
      A (Btx), as an adjunct to TMJ arthroscopy, in this patient population. MATERIALS
      AND METHODS: A retrospective cohort study was conducted of patients who underwent
      TMJ arthroscopy with (Btx group) or without (control group) intramuscular Btx for
      TMJ arthritis and refractory myofascial pain at the University of Michigan (Ann
      Arbor) from 2011 through 2014. For patients in the Btx group, intramuscular
      injections of Btx were administered at sites of maximal tenderness within the
      masseter and temporalis muscles. The primary outcome variable was pain score on
      the visual analog scale (VAS; 0 to 10). The secondary outcome variables included
      maximal interincisal opening, total score for sites of tenderness, total number
      of tender sites, and diet consistency tolerated. Statistical analysis included
      means and standard deviations, Student t test, simple regression analysis, and
      multiple regression analysis. RESULTS: The study cohort included 52 patients (30
      in Btx group, 22 in control group), of which 48 (92.3%) were women. The mean
      follow-up was 5.56 +/- 1.41 months. Patients in the Btx group had a significantly
      greater decrease in mean pain score (P = .04) on the VAS compared with the
      control group (score, 3.24 for Btx group; score, 1.13 for control group). On
      multivariate regression analysis, treatment with Btx trended toward significance
      (P = .084) and the preoperative pain score (P = .0007) was significantly
      correlated with the change in pain observed. CONCLUSION: The use of Btx appears
      to correlate with a clinically superior decrease in pain score compared with the
      control group. The use of Btx could be useful as an adjunctive treatment modality
      in the management of refractory myofascial pain.

PMID- 28500877
TI  - Clinically isolated aortitis: pitfalls, progress, and possibilities.
AB  - Non-infectious aortitis may be caused by several distinct systemic rheumatologic
      diseases. In some patients, aortitis is identified either pathologically or
      radiologically in the absence of clinical evidence of a systemic vasculitis. By
      consensus nomenclature, such cases are referred to as clinically isolated
      aortitis (CIA). Some systemic disorders may initially present as CIA including
      giant cell arteritis (GCA), IgG4-related disease, infectious aortitis, and
      granulomatosis with polyangiitis. CIA most commonly occurs in women of European
      descent over the age of 50 and, thus, mirrors the gender, age, and geographic
      distribution of GCA. CIA most often demonstrates a granulomatous/giant cell
      pattern of inflammation (GPI), and CIA-GPI is pathologically indistinguishable
      from aortitis due to GCA. In many cases, CIA may be a manifestation of
      extracranial GCA. CIA is being identified both pathologically in resected aortic
      tissue and radiologically by computed tomography scanning, magnetic resonance
      imaging, and fluorodeoxyglucose positron emission tomography. However, there
      appears to be significant differences between pathologically defined CIA and
      radiologically defined CIA. Multiple studies have shown that patients with CIA
      are at increased risk for subsequent aortic events (new aneurysms or dissections)
      and thus it is recommended to monitor these patients with periodic aortic
      imaging. While the data is currently limited, there is increasing evidence that
      at least some patients with CIA may benefit from immunosuppressive therapy.

PMID- 28500878
TI  - Identification of changes in neuronal function as a consequence of aging and
      tauopathic neurodegeneration using a novel and sensitive magnetic resonance
      imaging approach.
AB  - Tauopathies, the most common of which is Alzheimer's disease (AD), constitute the
      most crippling neurodegenerative threat to our aging population. Tauopathic
      patients have significant cognitive decline accompanied by irreversible and
      severe brain atrophy, and it is thought that neuronal dysfunction begins years
      before diagnosis. Our current understanding of tauopathies has yielded promising
      therapeutic interventions but have all failed in clinical trials. This is partly
      due to the inability to identify and intervene in an effective therapeutic window
      early in the disease process. A major challenge that contributes to the
      definition of an early therapeutic window is limited technologies. To address
      these challenges, we modified and adapted a manganese-enhanced magnetic resonance
      imaging (MEMRI) approach to provide sensitive and quantitative power to detect
      changes in broad neuronal function in aging mice. Considering that tau tangle
      burden correlates well with cognitive impairment in Alzheimer's patients, we
      performed our MEMRI approach in a time course of aging mice and an accelerated
      mouse model of tauopathy. We measured significant changes in broad neuronal
      function as a consequence of age, and in transgenic mice, before the deposition
      of bona fide tangles. This MEMRI approach represents the first diagnostic measure
      of neuronal dysfunction in mice. Successful translation of this technology in the
      clinic could serve as a sensitive diagnostic tool for the definition of effective
      therapeutic windows.

PMID- 28500879
TI  - Role of forensic medicine in evaluating non-fatal physical violence against women
      by their husbands in Jordan.
AB  - OBJECTIVE: Intimate partner violence against women is a major health problem in
      most nations, but to date, there has been little awareness of the extent or
      seriousness of this issue in Jordan. Forensic medical practitioners play a
      significant role in diagnosing, evaluating and reporting these cases. The
      Jordanian judicial system is dependent on forensic reports. This study aims to
      assess the role of forensic medicine in evaluating the physical injuries
      sustained by women who are abused by their husbands. METHOD: A retrospective
      review of 158 forensic reports of Jordanian women alleging assault by their
      husbands and who were seen at Jordan University Hospital over the period 2010
      2015. RESULTS: Of the 158 women who presented, 87 had multiple injuries. The
      majority of injuries were soft tissue injuries, but others included fractures,
      tympanic membrane perforation, burns and neck contusions. Twelve women were
      pregnant at the time of the assessment. The period of incapacity caused by these
      injuries (an important factor for the Jordanian judicial system) was between 1
      and 14 days. CONCLUSION: Intimate partner violence can present with a range of
      injuries from relatively minor to potentially disabling or life threatening.
      Forensic medicine has a role in documenting and evaluating these injuries and
      advising the judicial system in these cases. These are all key elements in
      increasing the awareness of the nature and extent of this behavior and its impact
      on women (and men) and the wider society.

PMID- 28500880
TI  - Motor functioning differentially predicts mortality in men and women.
AB  - INTRODUCTION: Research indicates gender differences in functional performance at
      advanced ages, but little is known about their impact on longevity for men and
      women. OBJECTIVE: To derive a set of motor function factors from a battery of
      functional performance measures and examine their associations with mortality,
      incorporating possible gender interactions. METHOD: Analyses were performed on
      the longitudinal Swedish Adoption/Twin Study of Aging (SATSA) including twenty
      four assessments of motor function up to six times over a 19-year period. Three
      motor factors were derived from several factor analyses; fine motor,
      balance/upper strength, and flexibility. A latent growth curve model was used to
      capture longitudinal age changes in the motor factors and generated estimates of
      intercept at age 70 (I), rates of change before (S1) and after age 70 (S2) for
      each factor. Cox regression models were used to determine how gender in
      interaction with the motor factors was related to mortality. RESULTS: Females
      demonstrated lower functional performance in all motor functions relative to men.
      Cox regression survival analyses demonstrated that both balance/upper strength,
      and fine motor function were significantly related to mortality. Gender specific
      analyses revealed that this was true for women only. For men, none of the motor
      factors were related to mortality. CONCLUSION: Women demonstrated more
      difficulties in all functioning facets, and only among women were motor
      functioning (balance/upper strength and fine motor function) associated with
      mortality. These results provide evidence for the importance of considering motor
      functioning, and foremost observed gender differences when planning for
      individualized treatment and rehabilitation.

PMID- 28500881
TI  - A Parvovirus B19 synthetic genome: sequence features and functional competence.
AB  - Central to genetic studies for Parvovirus B19 (B19V) is the availability of
      genomic clones that may possess functional competence and ability to generate
      infectious virus. In our study, we established a new model genetic system for
      Parvovirus B19. A synthetic approach was followed, by design of a reference
      genome sequence, by generation of a corresponding artificial construct and its
      molecular cloning in a complete and functional form, and by setup of an efficient
      strategy to generate infectious virus, via transfection in UT7/EpoS1 cells and
      amplification in erythroid progenitor cells. The synthetic genome was able to
      generate virus with biological properties paralleling those of native virus, its
      infectious activity being dependent on the preservation of self-complementarity
      and sequence heterogeneity within the terminal regions. A virus of defined genome
      sequence, obtained from controlled cell culture conditions, can constitute a
      reference tool for investigation of the structural and functional characteristics
      of the virus.

PMID- 28500883
TI  - Effect of temperature, water loading, and Ru/C catalyst on water-insoluble and
      water-soluble biocrude fractions from hydrothermal liquefaction of algae.
AB  - Hydrothermal liquefaction (HTL) converts algal biomass into a crude bio-oil
      (biocrude) and aqueous-phase products. The effect of temperature, water loading,
      and added H2 and/or Ru/C catalyst on the properties of the biocrude that
      spontaneously separates from the aqueous phase post reaction and also the
      biocrude that is extractable from the aqueous phase by dichloromethane is
      explored herein. This report is the first to elucidate how the yields,
      compositions, heating values, and energy recoveries of the two biocrudes vary
      with the processing conditions above. Increasing temperature from 350 to 400
      degrees C increased the yield of water-insoluble biocrude (38.1-42.5wt%) and its
      hexane-soluble subfraction (63.7-85.6wt%) while decreasing the yield of
      extractable, water-soluble biocrude (6.6-2.5wt%). The Ru/C catalyst had the same
      effect. Reaction temperature and catalysts could be used to manipulate the
      proportions of water-soluble and water-insoluble biocrude from algae HTL and
      thereby manipulate biocrude quantity and quality.

PMID- 28500882
TI  - Human papillomavirus 16 E6 and E7 oncoprotein expression alters microRNA
      expression in extracellular vesicles.
AB  - Extracellular vesicles released by cancer cells are mediators of intercellular
      communication that have been reported to contribute to carcinogenesis. Since they
      are readily detected in bodily fluids, they may also be used as cancer
      biomarkers. The E6/E7 oncoproteins drive human papillomavirus (HPV)-associated
      cancers, which account for approximately 5% of all human cancers worldwide. Here,
      we investigate how HPV16 E6/E7 oncogene expression in primary human epithelial
      cells alters miR expression in extracellular vesicles and compare these to
      changes in intracellular miR expression. Examining a panel of 68 cancer related
      miRs revealed that many miRs had similar expression patterns in cells and in
      extracellular vesicles, whereas some other miRs had different expression patterns
      and may be selectively packaged into extracellular vesicles. Interestingly, the
      set of miRs that may be selectively packaged in HPV16 E6/E7 extracellular
      vesicles is predicted to inhibit necrosis and apoptosis.

PMID- 28500884
TI  - Rapid biodiesel synthesis from waste pepper seeds without lipid isolation step.
AB  - In situ transformation of lipid in waste pepper seeds into biodiesel (i.e., fatty
      acid methyl esters: FAMEs) via thermally-induced transmethylation on silica was
      mainly investigated in this study. This study reported that waste pepper seeds
      contained 26.9wt% of lipid and that 94.1% of the total lipid in waste pepper
      seeds could be converted into biodiesel without lipid extraction step for only
      ~1min reaction time. This study also suggested that the optimal temperature for
      in situ transmethylation was identified as 390 degrees C. Moreover, comparison of
      in situ process via the conventional transmethylation catalyzed by H2SO4 showed
      that the introduced biodiesel conversion in this study had a higher tolerance
      against impurities, thereby being technically feasible. The in situ biodiesel
      production from other oil-bearing food wastes can be studied.

PMID- 28500885
TI  - Effects of ZnO nanoparticles on aerobic denitrification by strain Pseudomonas
      stutzeri PCN-1.
AB  - Anaerobic denitrification has been proved to be negatively affected by ZnO
      nanomaterials (NPs), but little is known about how ZnO NPs affects aerobic
      denitrification. In this study, inhibition of ZnO NPs to an aerobic denitrifier,
      Pseudomonas stutzeri PCN-1, was firstly reported. The results showed total
      nitrogen removal efficiency was decreased from 100% to 1.70% with the increase of
      ZnO NPs from 1 to 128mg/L. The presence of ZnO NPs caused significant inhibition
      of gene expressions and catalytic activities of nitrate reductase and nitrite
      reductase, which finally led to delayed nitrate reduction and high nitrite
      accumulation. Further studies revealed that the deposition of nanoparticles on
      the bacterial surface caused by electrostatic forces and the generation of
      reactive oxygen species (ROS) were responsible for the cytotoxicity of ZnO NPs,
      where ROS played a more important role. These results were of significance to
      evaluating the potential ecological toxicity and risks of nanomaterials.

PMID- 28500886
TI  - Optimized removal of oxytetracycline and cadmium from contaminated waters using
      chemically-activated and pyrolyzed biochars from forest and wood-processing
      residues.
AB  - In the present investigation, the adsorptive removal of the antibiotic drug
      oxytetracycline (OTC) and toxic heavy metal cadmium (Cd) from aqueous solution
      was carried out using forest and wood-processing residues. Numerous biochars were
      prepared using different chemical agents (H3PO4, H2SO4, NaOH and KOH) and
      pyrolysis times and temperatures. Several elemental, chemical and structural
      characterizations were performed. The optimum conditions for pyrolysis to enable
      the production of biochars with well-developed porosity was 600 degrees C for 1h,
      for both residues. The adsorption process using selected activated biochars was
      optimized with respect to reaction time, pH, temperature and initial load of
      pollutants. Under optimized operating conditions, and based on equilibrium
      modelling data, the biochars which showed the highest removal efficiencies of OTC
      and cadmium were "5M H3PO4 forest" (263.8mg/g) and "1M NaOH forest" (79.30mg/g),
      respectively. Compared to adsorbents reported in the literature, the efficiencies
      of those biochars are highly competitive.

PMID- 28500887
TI  - Integrated techno-economic and environmental analysis of butadiene production
      from biomass.
AB  - In this study, lignocellulose biorefineries annexed to a typical sugar mill were
      investigated to produce either ethanol (EtOH) or 1,3-butadiene (BD), utilizing
      bagasse and trash as feedstock. Aspen simulation of the scenarios were developed
      and evaluated in terms of economic and environmental performance. The minimum
      selling prices (MSPs) for bio-based BD and EtOH production were 2.9-3.3 and 1.26
      1.38-fold higher than market prices, respectively. Based on the sensitivity
      analysis results, capital investment, Internal Rate of Return and extension of
      annual operating time had the greatest impact on the MSP. Monte Carlo simulation
      demonstrated that EtOH and BD productions could be profitable if the average of
      ten-year historical price increases by 1.05 and 1.9-fold, respectively. The
      fossil-based route was found inferior to bio-based pathway across all
      investigated environmental impact categories, due to burdens associated with oil
      extraction.

PMID- 28500888
TI  - Impact of furan derivatives and phenolic compounds on hydrogen production from
      organic fraction of municipal solid waste using co-culture of Enterobacter
      aerogenes and E. coli.
AB  - In the present study, the effect of furan derivatives (furfural and 5
      hydroxymethylfurfural) and phenolic compounds (vanillin and syringaldehyde) on
      hydrogen production from organic fraction of municipal solid waste (OFMSW) was
      investigated using co-culture of facultative anaerobes Enterobacter aerogenes and
      E. coli. The inhibitors were applied in the concentration ranges of 0.25, 0.5, 1,
      2 and 5g/L each. Inhibition coefficients of phenolic compounds were higher than
      those of furan derivatives and vanillin exhibited maximum inhibition coefficients
      correspondingly lowest hydrogen yield among all inhibitors. Furfural and 5
      hydroxymethylfurfural addition resulted in an average decrease of 26.99% and
      37.16% in hydrogen yield respectively, while vanillin and syringaldehyde resulted
      in 49.40% and 42.26% average decrease in hydrogen yield respectively. Further
      analysis revealed that Furfural and 5-hydroxymethylfurfural were completely
      degraded up to concentrations of 1g/L, while vanillin and syringaldehyde were
      degraded completely up to the concentration of 0.5g/L. Volatile fatty acid
      generation decreased with inhibitors addition.

PMID- 28500889
TI  - Ammonium stimulates nitrate reduction during simultaneous nitrification and
      denitrification process by Arthrobacter arilaitensis Y-10.
AB  - The ability of Arthrobacter arilaitensis Y-10 for nitrogen removal from simulated
      wastewater was studied. Results showed that ammonium was the best inorganic
      nitrogen for strain Y-10's cell growth, which could also promote nitrate
      reduction. Approximately 100.0% of ammonium was removed in the nitrogen removal
      experiments. The nitrate removal efficiency was 73.3% with nitrate as sole
      nitrogen source, and then the nitrate efficiency was increased to 85.3% and
      100.0% with ammonium and nitrate (both about 5 or 100mg/L) as the mixed nitrogen
      sources. Nitrite accumulation was observed in presence of ammonium and nitrate.
      When the concentration of sole nitrite nitrogen was 10.31mg/L, the nitrite
      removal efficiency was 100.0%. Neither ammonium nor nitrate was accumulated
      during the whole experimental process. All experimental results indicated that A.
      arilaitensis Y-10 could remove ammonium, nitrate and nitrite at 15 degrees C from
      wastewater, and could also perform simultaneous nitrification and denitrification
      under aerobic condition.

PMID- 28500890
TI  - Effect of static magnetic field on trichloroethylene removal in a biotrickling
      filter.
AB  - A laboratory-scale biotrickling filter combined with a magnetic field (MF-BTF)
      and a single BTF (S-BTF) were set up to treat trichloroethylene (TCE) gas. The
      influences of phenol alone and NaAc-phenol as co-substrates and different MF
      intensities were investigated. At low MF intensity, MF-BTF displayed better
      performance with 0.20g/L of phenol, 53.6-337.1mg/m3 of TCE, and empty bed
      residence times of 202.5s. The performances followed the order MF-BTF (60.0mT)>MF
      BTF (30.0mT)>S-BTF (0mT)>MF-BTF (130.0mT), and the removal efficiencies (REs) and
      maximum elimination capacities (ECs) corresponded to: 92.2%-45.5%, 2656.8mg/m3h;
      89.8%-37.2%, 2169.1mg/m3h; 89.8%-29.8%, 1967.7mg/m3h; 76.0%-20.8%, 1697.1mg/m3h,
      respectively. High-throughput sequencing indicated that the bacterial diversity
      was lower, whereas the relative abundances of Acinetobacter, Chryseobacterium,
      and Acidovorax were higher in MF-BTF. Results confirmed that a proper MF could
      improve TCE removal performance in BTF.

PMID- 28500891
TI  - Steam-exploded biomass saccharification is predominately affected by
      lignocellulose porosity and largely enhanced by Tween-80 in Miscanthus.
AB  - In this study, total ten Miscanthus accessions exhibited diverse cell wall
      compositions, leading to largely varied hexoses yields at 17%-40% (% cellulose)
      released from direct enzymatic hydrolysis of steam-exploded (SE) residues.
      Further supplied with 2% Tween-80 into the enzymatic digestion, the Mis7
      accession showed the higher hexose yield by 14.8-fold than that of raw material,
      whereas the Mis10 had the highest hexoses yield at 77% among ten Miscanthus
      accessions. Significantly, this study identified four wall polymer features that
      negatively affect biomass saccharification as p<0.05 or 0.01 in the SE residues,
      including cellulose DP, Xyl and Ara of hemicellulose, and S-monomer of lignin.
      Based on Simons' stain, the SE porosity (defined by DY/DB) was examined to be the
      unique positive factor on biomass enzymatic digestion. Hence, this study provides
      the potential strategy to enhance biomass saccharification using optimal biomass
      process technology and related genetic breeding in Miscanthus and beyond.

PMID- 28500892
TI  - Enrichment of extremophilic exoelectrogens in microbial electrolysis cells using
      Red Sea brine pools as inocula.
AB  - Applying microbial electrochemical technologies for the treatment of highly
      saline or thermophilic solutions is challenging due to the lack of proper inocula
      to enrich for efficient exoelectrogens. Brine pools from three different
      locations (Valdivia, Atlantis II and Kebrit) in the Red Sea were investigated as
      potential inocula sources for enriching exoelectrogens in microbial electrolysis
      cells (MECs) under thermophilic (70 degrees C) and hypersaline (25% salinity)
      conditions. Of these, only the Valdivia brine pool produced high and consistent
      current 6.8+/-2.1A/m2-anode in MECs operated at a set anode potential of +0.2V
      vs. Ag/AgCl (+0.405V vs. standard hydrogen electrode). These results show that
      exoelectrogens are present in these extreme environments and can be used to
      startup MEC under thermophilic and hypersaline conditions. Bacteroides was
      enriched on the anode of the Valdivia MEC, but it was not detected in the open
      circuit voltage reactor seeded with the Valdivia brine pool.

PMID- 28500893
TI  - Glucagon receptor knockout mice are protected against acute olanzapine-induced
      hyperglycemia.
AB  - OBJECTIVES: To determine if glucagon is involved in mediating the increase in
      blood glucose levels caused by the second-generation antipsychotic drug
      olanzapine. MATERIALS AND METHODS: Whole body glucagon receptor deficient mice
      (Gcgr-/-) or WT littermate controls were injected with olanzapine (5mg/kg BW IP)
      and changes in blood glucose measured over the following 120min. Separate cohorts
      of mice were treated with olanzapine and changes in pyruvate tolerance, insulin
      tolerance and whole body substrate oxidation were determined. RESULTS: Olanzapine
      treatment increased serum glucagon and lead to rapid increases in blood glucose
      concentrations in WT mice. Gcgr-/- mice were protected against olanzapine-induced
      increases in blood glucose but this was not explained by differences in terminal
      serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle,
      adipose tissue or liver or differences in RER. In both genotypes olanzapine
      induced an equivalent degree of insulin resistance as measured using an insulin
      tolerance test. Olanzapine treatment led to an exaggerated glucose response to a
      pyruvate challenge in WT but not Gcgr-/- mice and this was paralleled by
      reductions in the protein content of PEPCK and G6Pase in livers from Gcgr-/-
      mice. CONCLUSIONS: Gcgr-/- mice are protected against olanzapine-induced
      increases in blood glucose. This is likely a result of reductions in liver
      glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein
      content. Our findings highlight the central role of the liver in mediating
      olanzapine-induced disturbances in glucose homeostasis.

PMID- 28500894
TI  - Mercury induced oxidative stress, DNA damage, and activation of antioxidative
      system and Hsp70 induction in duckweed (Lemna minor).
AB  - Mercury uptake and its effects on physiology, biochemistry and genomic stability
      were investigated in Lemna minor after 2 and 6d of exposure to 0-30MUM Hg. The
      accumulation of Hg increased in a concentration- and duration-dependent manner,
      and was positively correlated with the leaf damage. Oxidative stress after Hg
      exposure was evidenced in L. minor by a significant decrease in photosynthetic
      pigments, an increase in malondialdehyde and lipoxygenase activities (total
      enzyme activity and isoenzymes activity). Fronds of L. minor exposed to Hg showed
      an induction of peroxidase, catalase, and ascorbate peroxidase activities (total
      enzyme activity and some isoenzymes activities). Exposure of L. minor to Hg
      reduced the activity (total enzyme activity and some isoenzymes activities) of
      glutathione reductase, and superoxide dismutase. Exposure to Hg produced a
      transient increase in the content of glutathione and ascorbic acid. The content
      of dehydroascorbate and oxidized glutathione in L. minor were high during the
      entire exposure period. Exposure of L. minor to Hg also caused the accumulation
      of proline and soluble sugars. The amplification of new bands and the absence of
      normal DNA amplicons in treated plants in the random amplified polymorphic DNA
      (RAPD) profile indicated that genomic template stability (GTS) was affected by Hg
      treatment. The accumulation of Hsp70 indicated the occurrence of a heat shock
      response at all Hg concentrations. These results suggest that L. minor plants
      were able to cope with Hg toxicity through the activation of various mechanisms
      involving enzymatic and non-enzymatic antioxidants, up-regulation of proline, and
      induction of Hsp70.

PMID- 28500895
TI  - A universal multilingual weightless neural network tagger via quantitative
      linguistics.
AB  - In the last decade, given the availability of corpora in several distinct
      languages, research on multilingual part-of-speech tagging started to grow.
      Amongst the novelties there is mWANN-Tagger (multilingual weightless artificial
      neural network tagger), a weightless neural part-of-speech tagger capable of
      being used for mostly-suffix-oriented languages. The tagger was subjected to
      corpora in eight languages of quite distinct natures and had a remarkable
      accuracy with very low sample deviation in every one of them, indicating the
      robustness of weightless neural systems for part-of-speech tagging tasks.
      However, mWANN-Tagger needed to be tuned for every new corpus, since each one
      required a different parameter configuration. For mWANN-Tagger to be truly
      multilingual, it should be usable for any new language with no need of parameter
      tuning. This article proposes a study that aims to find a relation between the
      lexical diversity of a language and the parameter configuration that would
      produce the best performing mWANN-Tagger instance. Preliminary analyses suggested
      that a single parameter configuration may be applied to the eight aforementioned
      languages. The mWANN-Tagger instance produced by this configuration was as
      accurate as the language-dependent ones obtained through tuning. Afterwards, the
      weightless neural tagger was further subjected to new corpora in languages that
      range from very isolating to polysynthetic ones. The best performing instances of
      mWANN-Tagger are again the ones produced by the universal parameter
      configuration. Hence, mWANN-Tagger can be applied to new corpora with no need of
      parameter tuning, making it a universal multilingual part-of-speech tagger.
      Further experiments with Universal Dependencies treebanks reveal that mWANN
      Tagger may be extended and that it has potential to outperform most state-of-the
      art part-of-speech taggers if better word representations are provided.

PMID- 28500897
TI  - Genetic alterations within TLR genes in development of Toxoplasma gondii
      infection among Polish pregnant women.
AB  - PURPOSE: The research was conducted to evaluate the role of genotypes, haplotypes
      and multiple-SNP variants in the range of TLR2, TLR4 and TLR9 single nucleotide
      polymorphisms (SNPs) in the development of Toxoplasma gondii infection among
      Polish pregnant women. MATERIAL AND METHODS: The study was performed for 116
      Polish pregnant women, including 51 patients infected with T. gondii, and 65 age
      matched control pregnant individuals. Genotypes in TLR2 2258 G>A, TLR4 896 A>G,
      TLR4 1196 C>T and TLR9 2848 G>A SNPs were estimated by self-designed, nested PCR
      RFLP assays. Randomly selected PCR products, representative for distinct
      genotypes in the studied polymorphisms, were confirmed by sequencing. All the
      genotypes were calculated for Hardy-Weinberg (H-W) equilibrium and TLR4 variants
      were tested for linkage disequilibrium. Relationships were assessed between
      alleles, genotypes, haplotypes or multiple-SNP variants in TLR polymorphisms and
      the occurrence of T. gondii infection in pregnant women, using a logistic
      regression model. RESULTS: All the analyzed genotypes preserved the H-W
      equilibrium among the studied groups of patients (P>0.050). Similar distribution
      of distinct alleles and individual genotypes in TLR SNPs, as well as of
      haplotypes in TLR4 polymorphisms, were observed in T. gondii infected and control
      uninfected pregnant women. However, the GACG multiple-SNP variant, within the
      range of all the four studied polymorphisms, was correlated with a decreased risk
      of the parasitic infection (OR 0.52, 95% CI 0.28-0.97; P<=0.050). CONCLUSIONS:
      The polymorphisms, located within TLR2, TLR4 and TLR9 genes, may be involved
      together in occurrence of T. gondii infection among Polish pregnant women.

PMID- 28500896
TI  - A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in
      Breast Cancer.
AB  - The transformation of a normal cell to cancer requires the derail of multiple
      pathways. Normal signaling in a cell is regulated at multiple stages by the
      presence of feedback loops, calibration of levels of proteins by their regulated
      turnover, and posttranscriptional regulation, to name a few. The tumor suppressor
      protein FBXO31 is a component of the SCF E3 ubiquitin ligase and is required to
      arrest cells at G1 following genotoxic stresses. Due to its growth-suppression
      activity, it is underexpressed in many cancers. However, the molecular mechanism
      underlying the translational regulation of FBXO31 remains unclear. Here we show
      that the oncogenic microRNAs miR-93 and miR-106a repress FBXO31, resulting in the
      upregulation of Slug, which is involved in epithelial-mesenchymal transition and
      cell invasion. FBXO31 targets and ubiquitylates Slug for proteasomal degradation.
      However, this mechanism is repressed in breast tumors where miR-93 and miR-106a
      are overexpressed. Our study further unravels an interesting mechanism whereby
      Slug drives the expression of miR-93 and miR-106a, thus establishing a positive
      feedback loop to maintain an invasive phenotype. Together, these results
      establish the presence of interplay between microRNAs and the ubiquitination
      machinery, which together regulate cancer cell invasion.

PMID- 28500898
TI  - The fact not to ignore: Mean blood pressure is the main predictor of increased
      arterial stiffness in patients with systemic rheumatic diseases.
AB  - PURPOSE: We aimed to evaluate the association between carotid-radial pulse wave
      velocity (PWV), augmentation index (AIx), and flow-mediated dilatation (FMD) of
      the brachial artery and factors potentially influencing them in patients with
      rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic
      sclerosis (SSc). MATERIAL AND METHODS: 316 patients diagnosed with RA (32%), SLE
      (20%), SSc (16%) and 156 controls (32%) were included in the study. Parameters of
      arterial stiffness AIx and PWV were obtained using applanation tonometry. FMD
      reflecting endothelial function was measured by ultrasound. RESULTS: AIx was
      increased in all three diseases (p<0.0001), but no differences were found between
      rheumatic diseases. In most of the RA cases PWV values were abnormal (on average
      by 0.52m/sec higher than in controls), while in SSc patients FMD values were
      diminished (p=0.006). Mean blood pressure (MBP) was the most consistent
      predictive factor in all three diseases, influencing both PWV and AIx, although
      patient age was also important in variation of AIx. The disease activity score
      (DAS28) was relevant only in RA patients. Furthermore, SLE disease activity index
      in SLE or Rodnan skin thickness score had no statistical significance in SSc and
      inflammatory markers. CONCLUSIONS: Both, PWV and AIx are dependent on MBP and age
      DAS28 may affect AIx in RA patients, while other disease or inflammatory markers
      are unlikely to have any effect. MBP is one of the main cardiovascular risk
      factors affecting the arterial stiffness in RA, SLE and SSc patients therefore
      controlling MBP in systemic rheumatic disease patients is mandatory.

PMID- 28500899
TI  - Hysteroscopy in the treatment of uterine cesarean section scar diverticulum: A
      systematic review.
AB  - The aim of this paper is to review and to analyze the results of previous studies
      dealing with hysteroscopic treatment of postcesarean scar defects. A systematic
      review of publications indexed in MEDLINE/PubMed database identified a total of
      11 studies dealing with resectoscopic treatment of postcesarean scar defect. The
      review was conducted in line with the Meta-analysis of Observational Studies in
      Epidemiology (MOOSE) guidelines and the PRISMA statement. In only few studies,
      patients were qualified for hysteroscopic surgery based on the measurement of the
      defect depth and thickness of residual myometrium above the pouch. Two principal
      techniques were used for the hysteroscopic treatment: resection of one edge of
      the scar diverticulum, and resection of the inferior and superior edges of the
      defect. Additionally, most authors performed electrocauterization of the niche
      bottom. Resectoscopic treatment turned out to be highly effective in the case of
      women with AUB. No complications of the hysteroscopic procedure have been
      reported. Methodological value of the reviewed studies was relatively low due to
      non-unified selection/verification criteria and incomplete, non-systematic
      postoperative assessment. In conclusion, hysteroscopic treatment seems to be a
      promising option in the management of postcesarean scar defects, but still
      further research is needed on the problem in question.

PMID- 28500900
TI  - Treatment of refractory epilepsy patients with autologous mesenchymal stem cells
      reduces seizure frequency: An open label study.
AB  - PURPOSE: Existing anti-epileptic drugs (AED) have limited efficiency in many
      patients, necessitating the search for alternative approaches such as stem cell
      therapy. We report the use of autologous patient-derived mesenchymal stem cells
      (MSC) as a therapeutic agent in symptomatic drug-resistant epilepsy in a Phase I
      open label clinical trial (registered as NCT02497443). PATIENTS AND METHODS: The
      patients received either standard treatment with AED (control group), or AED
      supplemented with single intravenous administration of undifferentiated
      autologous MSC (target dose of 1*106cells/kg), followed by a single intrathecal
      injection of neurally induced autologous MSC (target dose of 0.1*106cells/kg).
      RESULTS: MSC injections were well tolerated and did not cause any severe adverse
      effects. Seizure frequency was designated as the main outcome and evaluated at 1
      year time point. 3 out of 10 patients in MSC therapy group achieved remission (no
      seizures for one year and more), and 5 additional patients became responders to
      AEDs, while only 2 out of 12 patients became responders in control group
      (difference significant, P=0.0135). CONCLUSIONS: MSC possess unique
      immunomodulatory properties and are a safe and promising candidate for cell
      therapy in AED resistant epilepsy patients.

PMID- 28500901
TI  - The course of cancer related fatigue up to ten years in early breast cancer
      patients: What impact in clinical practice?
AB  - Little is known about the cancer related fatigue (CRF) along cancer course and
      risk factors that could predict CRF development and persistence in breast cancer
      (BC) survivors. This prospective study detected incidence, timing of onset,
      duration of CRF, impact on QoL and psychological distress. Seventy-eight early BC
      patients, undergoing chemotherapy (CT) followed or not by hormonal therapy were
      assessed for QoL and psychological distress by EORTC QLQC30 and HADs
      questionnaires. Fatigue was investigated with mix methods, structured interview
      and psychometric measures. A qualitative analysis was added to assess the
      behavioral pattern of CRF. Low fatigue levels were identified after surgery (9%),
      increasing during (49%) and at the end of CT (47%), maintaining after 1 year
      (31%) and declining up to ten years of follow-up. Prevalence of CRF was higher at
      the end of CT and lower at follow-up. At the end and after 1 and 2 years from CT,
      persistence of CRF was associated to anxiety in 20%, 11% and 5% and to depression
      in 15%, 10% and 5% respectively. A relationship between CRF and psychological
      distress was observed; patients presenting depression and anxiety before CT were
      at higher risk for fatigue onset at a later period. A relationship between
      fatigue and QoL was noted at the end of CT. Our study shows the fatigue timely
      trend in early BC patients from surgery, CT and follow-up. Identification of
      biological, psychological, social predictor factors related to fatigue could be
      helpful for early interventions in patients at higher risk of developing fatigue.

PMID- 28500902
TI  - RNA-sequencing and pathway analysis reveal alteration of hepatic steroid
      biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow
      (Gobiocypris rarus).
AB  - Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse
      effects of TBT on reproduction and lipogenesis are observed in fishes, the
      underlying mechanisms, especially in livers, are still scarce and inconclusive.
      Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male
      rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially
      expressed genes were identified, enrichment analysis and validation by
      quantitative real-time PCR were conducted. The results showed that TBT up
      regulated the profile of hepatic genes in the steroid biosynthesis pathway and
      down-regulated the profile of hepatic genes in the retinol metabolism pathway. In
      the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of
      cholesterol, which could affect the bioavailability of steroid hormones. More
      important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis
      of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic
      retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays
      essential roles in both reproduction and lipogenesis. The results of two pathways
      offered new mechanisms underlying the toxicology of TBT and represented a
      starting point from which detailed mechanistic links should be explored.

PMID- 28500904
TI  - Endometrial adenocarcinoma recurrence presenting with tibial metastasis: Report
      of a case.
AB  - INTRODUCTION: Metastatic bone disease at extremities is mostly associated with
      lung, liver, prostat, thyriod or breast malignancies. There for surgeons
      generally tends to seek for a primary tumor originating from these organs. Herein
      a case of endometrial adenocarcinoma recurrence that presented with symptoms of
      tibial pain is described. PRESENTATION OF CASE: 59 year-old woman was admitted to
      our orthopaedic oncology unit with pain, swelling and tenderness at right cruris
      for two weeks without any trauma history. Her medical history revealed that she
      had a total abdominal hysterectomy and bilateral salpingo-oophorectomy. During
      follow-ups no recurrence had been detected. Initial X-rays of the right tibia
      showed a lytic and expansile mass located at the shaft of the tibia suggesting
      metastasis. A wide resection of the lesion with clear margins was performed two
      weeks after first admittance. Resected area was replaced by fresh frozen femoral
      shaft allograft. At postoperative 17th month. X-rays obtained at last follow-up
      demostrated full healing and integration of allograft. DISCUSSION: Endometrial
      adenocarcinoma is a disease of postmenapousal women with 95% of the cases
      occurring after the age of 40 years. Patients with advanced or recurrent
      endometrial cancer often have distant metastases found within the lymph nodes,
      liver, and/or lung. CONCLUSION: Recurrence of endometrial cancer as a solitary
      bone lesion is a rare situation. Wide resection and reconstruction with an
      allograft or an intercalar prosthesis might be an option to increase survival and
      possible cure of the patient.

PMID- 28500905
TI  - Double acousto-optic deflector system for increased scanning range of laser
      beams.
AB  - A new laser scanning system is presented based on two wide-band acousto-optic
      deflectors. The interaction medium is tellurium dioxide. Anisotropic interactions
      take place under two different tangential phase matching configurations in such a
      way that the acousto-optic bandwidths add up. We demonstrate the feasibility of
      such a cascade deflection system for the wavelength of lambda=514nm. The total
      frequency bandwidth is Deltaf=100MHz, equally distributed between the two acousto
      optic deflectors. The total angular scan at the output is Deltatheta=4.4 degrees 
      leading to 125 resolvable spots for a 1mm truncated Gaussian beam.

PMID- 28500903
TI  - Microcystin-LR bioconcentration induces antioxidant responses in the digestive
      gland of two marine bivalves Crassostrea gigas and Mytilus edulis.
AB  - Microcystins (MCs) are a major group of potent cyanobacterial toxins found in
      freshwater and even brackish waterbodies. To understand the putative correlation
      between bioconcentration of MCs and antioxidant responses of the digestive gland
      of bivalves, Pacific oyster Crassostrea gigas and blue mussel Mytilus edulis were
      exposed to different concentrations (0.1, 1, 10 and 20MUgL-1) of MC-Leucine
      Arginine (LR) for seven days. MC-LR bioconcentrated in the digestive glands of
      both bivalves during exposure period. The levels were slightly reduced when the
      bivalves were exposed to seawater during depuration (7days), while approximately
      0.1MUgL-1 of MC-LR was observed in the 10 and 20MUgL-1 exposed bivalves at the
      end of depuration. Intracellular malondialdehyde (MDA) and glutathione (GSH)
      levels were significantly elevated in the 10 and 20MUgL-1 exposed bivalves at
      7day, and the levels were maintained during depuration in both bivalves. Overall,
      significant higher levels of enzymatic activities of antioxidant defense systems
      such as glutathione S-transferase (GST), catalase (CAT), superoxide dismutase
      (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) were observed
      in the 10 and 20MUgL-1 exposed bivalves. Interestingly, most of higher levels of
      Pacific oyster were detected at exposure period, while blue mussel showed higher
      levels at depuration phase, suggesting a species-specific sensitivity upon MC-LR.
      These patterns were correlated with the bioconcentration patterns of MC-LR as
      Pacific oyster was highly accumulated by MC-LR during exposure period, but blue
      mussel showed prolonged high levels of MC-LR for depuration phase. Our results
      will be useful to understand species-specific bioconcentration of MC-LR in
      bivalves and their effects on intracellular oxidative status via accumulation.

PMID- 28500906
TI  - Feasibility and reliability of a mobile tool to evaluate exposure to tobacco
      product marketing and messages using ecological momentary assessment.
AB  - INTRODUCTION: Existing measures of tobacco marketing and messaging exposure are
      limited, relying on recall, recognition, or proxy measures. This study aimed to
      determine the feasibility and reliability of a mobile application for the
      measurement of tobacco and e-cigarette marketing and message exposure using
      ecological momentary assessment (EMA). METHODS: Young adults from Austin, TX
      (n=181, ages 18-29) were instructed to use a mobile application to record all
      sightings of marketing or social media related to tobacco (including e
      cigarettes) in real-time for 28days (Event EMAs). Tobacco product use and recall
      of message encounters were assessed daily using an app-initiated EMA (Daily
      EMAs). RESULTS: The mobile app was a feasible and acceptable method to measure
      exposure to tobacco messages. The majority of messages (45.0%) were seen on the
      Internet, and many were user-generated. Thirty-day recall of messages at baseline
      was poorly correlated with messages reported via Event EMA during the study
      period; however, the correlation between post-study 30-day recall and Event EMA
      was much stronger (r=0.603 for industry-sponsored messages, r=0.599 for user
      generated messages). Correlations between Daily EMAs and 30-day recall of message
      exposure (baseline and post-study) were small (baseline: r=0.329-0.389) to large
      (post-study: r=0.656-0.766). CONCLUSIONS: These findings suggest that EMA is a
      feasible and reliable method for measuring tobacco message exposure, especially
      given the prevalence of messages encountered online and on social media. Recall
      measures are limited in their ability to accurately represent marketing exposure,
      but might be improved by a period of priming or clearer response categories.

PMID- 28500907
TI  - In the process of drinking to cope among college students: An examination of
      specific vs. global coping motives for depression and anxiety symptoms.
AB  - The present study sought to address an issue in the drinking to cope (DTC)
      motives literature, namely the inconsistent application of treating DTC motives
      as a single construct and splitting it into DTC-depression and DTC-anxiety
      motives. Specifically, we aimed to determine if the effects of anxiety and
      depression on alcohol-related problems are best explained via their associations
      with DTC with specific affects or via their associations with a more global
      measure of DTC by testing four distinct models: the effects of anxiety/depression
      on alcohol-related problems mediated by DTC-anxiety only (Model 1), these effects
      mediated by DTC-depression only (Model 2), these effects mediated by a combined,
      global DTC factor (Model 3), and these effects mediated by both DTC-anxiety and
      DTC-depression (Model 4). Using path analysis/structural equation modeling across
      two independent samples, we found that there was a significant total indirect
      effect of both anxiety and depressive symptoms on alcohol-related problems in
      every model. However, there was a slightly larger indirect effect in all models
      using the global DTC motives factor compared to even the model that included the
      two distinct DTC motives. Our results provide some preliminary evidence that at
      least at the between-subjects level, a global DTC motives factor may have more
      predictive validity than separate DTC motives. Additional research is needed to
      examine how to best operationalize DTC motives at different levels of analysis
      (e.g., within-subjects vs. between subjects) and in different populations (e.g.,
      college students vs. individuals with alcohol use disorder).

PMID- 28500908
TI  - Distress tolerance interacts with circumstances, motivation, and readiness to
      predict substance abuse treatment retention.
AB  - BACKGROUND: Our understanding of the conditions that influence substance abuse
      treatment retention in urban African American substance users is limited. This
      study examined the interacting effect of circumstances, motivation, and readiness
      (CMR) with distress tolerance to predict substance abuse treatment retention in a
      sample of urban African American treatment-seeking substance users. METHODS: Data
      were collected from 81 African American substance users entering residential
      substance abuse treatment facility in an urban setting. Participants completed
      self-reported measures on CMR and distress tolerance. In addition, participants
      were assessed on psychiatric comorbidities, substance use severity, number of
      previous treatments, and demographic characteristics. Data on substance abuse
      treatment retention were obtained using administrative records of the treatment
      center. RESULTS: Logistic regression analysis found that the interaction of CMR
      and distress tolerance was significant in predicting substance abuse treatment
      retention. Higher score on CMR was significantly associated with increased
      likelihood of treatment retention in substance users with higher distress
      tolerance, but not in substance users with lower distress tolerance. CONCLUSIONS:
      Findings of the study indicate that at higher level of distress tolerance,
      favorable external circumstances, higher internal motivation, and greater
      readiness to treatment are important indicators of substance abuse treatment
      retention. The study highlights the need for assessing CMR and distress tolerance
      levels among substance users entering treatment, and providing targeted
      interventions to increase substance abuse treatment retention and subsequent
      recovery from substance abuse among urban African American substance users.

PMID- 28500909
TI  - Development and testing of a moment-based coactivation index to assess complex
      dynamic tasks for the lumbar spine.
AB  - BACKGROUND: Many methods exist to describe coactivation between muscles. However,
      most methods have limited capability in the assessment of coactivation during
      complex dynamic tasks for multi-muscle systems such as the lumbar spine. The
      ability to assess coactivation is important for the understanding of
      neuromuscular inefficiency. In the context of this manuscript, inefficiency is
      defined as the effort or level of coactivation beyond what may be necessary to
      accomplish a task (e.g., muscle guarding during postural stabilization). The
      objectives of this study were to describe the development of an index to assess
      coactivity for the lumbar spine and test its ability to differentiate between
      various complex dynamic tasks. METHODS: The development of the coactivation index
      involved the continuous agonist/antagonist classification of moment contributions
      for the power-producing muscles of the torso. Different tasks were employed to
      test the range of the index including lifting, pushing, and Valsalva. FINDINGS:
      The index appeared to be sensitive to conditions where higher coactivation would
      be expected. These conditions of higher coactivation included tasks involving
      higher degrees of control. Precision placement tasks required about 20% more
      coactivation than tasks not requiring precision, lifting at chest height required
      approximately twice the coactivation as mid-thigh height, and pushing fast speeds
      with turning also required at least twice the level of coactivity as slow or
      preferred speeds. INTERPRETATION: Overall, this novel coactivation index could be
      utilized to describe the neuromuscular effort in the lumbar spine for tasks
      requiring different degrees of postural control.

PMID- 28500910
TI  - Ankle strength impairments associated with knee osteoarthritis.
AB  - BACKGROUND: Knee Osteoarthritis seems to negatively impact ankle biomechanics.
      However, the effect of knee osteoarthritis on ankle muscle strength has not been
      clearly established. This study aimed to evaluate the ankle strength of the
      plantar flexors and dorsiflexors of patients with knee osteoarthritis in
      different degrees of severity. METHODS: Thirty-seven patients with knee
      osteoarthritis and 15 controls, subjected to clinical and radiographic analysis,
      were divided into three groups: control, mild, and moderate knee osteoarthritis.
      Participants answered a self-reported questionnaire and accomplished a muscle
      torque assessment of the ankle using the Biodex dynamometer in isometric,
      concentric and eccentric modes. FINDINGS: The mild osteoarthritis group (peak
      torque=26.85(SD 3.58)) was significantly weaker than the control (peak
      torque=41.75(SD 4.42)) in concentric plantar flexion (P<0.05). The control and
      mild osteoarthritis groups were not significantly different from the moderate
      osteoarthritis group (peak torque=36.12(SD 4.61)) in concentric plantar flexion.
      There were no significant differences for dorsiflexion among the groups; however
      the control and moderate osteoarthritis groups presented large and medium
      standardized mean differences. The mild osteoarthritis group was significantly
      lower than the control and moderate osteoarthritis groups in the concentric
      plantar flexion by concentric dorsiflexion torque ratio. INTERPRETATION: Ankle
      function exhibited impairments in patients with knee osteoarthritis, especially
      in the plantar flexion torque, in which the mild osteoarthritis group was weaker
      than the control. Interestingly, patients with moderate knee osteoarthritis
      showed results similar to the control group in plantar flexion torque. The
      results raise the possibility of a compensatory mechanism of the plantar flexors
      developed by patients in more advanced degrees to balance other muscle failures.

PMID- 28500911
TI  - Do welfare regimes matter for oral health? A multilevel analysis of European
      countries.
AB  - While the role of political factors on population health has recently received
      increasing attention, relatively little is known in that respect for oral health.
      We aimed to assess the influence of welfare state regimes on the variation in
      adult oral health between European countries, building on the existing literature
      by using a multilevel approach. Our analysis also explored how the oral health of
      people with different socioeconomic position was influenced by living in five
      different welfare state regimes. We analysed data from the Eurobarometer survey
      2009. The main outcome was no functional dentition, defined as having fewer than
      20 natural teeth. Age, gender, marital status, education and occupational social
      class were the individual-level explanatory variables, while welfare regimes, GDP
      per capita and GDP annual growth were the country-level variables. Multilevel
      logistic regression models were fitted with individuals nested within countries.
      Results revealed that country-level characteristics accounted for 8.1% of the
      variation in oral health. Adults in all welfare regimes were more likely to have
      poorer oral health than their counterparts in the Scandinavian regime, with those
      in Eastern countries being 6.94 (95% CI: 3.62-12.67) times as likely to lack a
      functional dentition as adults in Scandinavian countries. The variation at
      country-level reduced significantly when welfare regimes were introduced into the
      model (from 0.57 to 0.16; 72% reduction), indicating that welfare regime
      explained much of the variation in the outcome among European countries. Finally,
      adults with less education and lower occupational level were more likely to have
      no functional dentition, especially in the Eastern and Bismarckian welfare
      regimes.

PMID- 28500912
TI  - Clotting time-dependent pseudohyperkalemia associated with Sezary syndrome.

PMID- 28500914
TI  - Limitations of experiments performed in artificially made OECD standard soils for
      predicting cadmium, lead and zinc toxicity towards organisms living in natural
      soils.
AB  - Development of comparative toxicity potentials of cationic metals in soils for
      applications in hazard ranking and toxic impact assessment is currently
      jeopardized by the availability of experimental effect data. To compensate for
      this deficiency, data retrieved from experiments carried out in standardized
      artificial soils, like OECD soils, could potentially be tapped as a source of
      effect data. It is, however, unknown whether such data are applicable to natural
      soils where the variability in pore water concentrations of dissolved base
      cations is large, and where mass transfer limitations of metal uptake can occur.
      Here, free ion activity models (FIAM) and empirical regression models (ERM, with
      pH as a predictor) were derived from total metal EC50 values (concentration with
      effects in 50% of individuals) using speciation for experiments performed in
      artificial OECD soils measuring ecotoxicological endpoints for terrestrial
      earthworms, potworms, and springtails. The models were validated by predicting
      total metal based EC50 values using backward speciation employing an independent
      set of natural soils with missing information about ionic composition of pore
      water, as retrieved from a literature review. ERMs performed better than FIAMs.
      Pearson's r for log10-transformed total metal based EC50s values (ERM) ranged
      from 0.25 to 0.74, suggesting a general correlation between predicted and
      measured values. Yet, root-mean-square-error (RMSE) ranged from 0.16 to 0.87 and
      was either smaller or comparable with the variability of measured EC50 values,
      suggesting modest performance. This modest performance was mainly due to the
      omission of pore water concentrations of base cations during model development
      and their validation, as verified by comparisons with predictions of published
      terrestrial biotic ligand models. Thus, the usefulness of data from artificial
      OECD soils for global-scale assessment of terrestrial ecotoxic impacts of Cd, Pb
      and Zn in soils is limited due to relatively small variability of pore water
      concentrations of dissolved base cations in OECD soils, preventing their
      inclusion in development of predictive models. Our findings stress the importance
      of considering differences in ionic composition of soil pore water when
      characterizing terrestrial ecotoxicity of cationic metals in natural soils.

PMID- 28500915
TI  - A comparison of denitrifying bacterial community structures and abundance in
      acidic soils between natural forest and re-vegetated forest of Nanling Nature
      Reserve in southern China.
AB  - Denitrification plays a key role in converting reactive nitrogen species to
      dinitrogen gas back into the atmosphere to maintain the equilibrium of nitrogen
      cycling in ecosystems. In this study, functional genes of nirK and nosZ were used
      to detect the community structure and abundance of denitrifying microorganisms in
      acidic forest soils in southern China. Three sets of factors were considered for
      a comparison among 5 forests, including forest types (natural vs. re-vegetated),
      depths (surface layer vs. lower layer) and seasons (winter vs. summer). The
      community of nirK gene detected from these acidic forest soils was closely
      related to Proteobacteria especially alpha-Proteobacteria and uncultured soil
      sequences, while that of nosZ gene was affiliated with the alpha-, beta- and
      gamma-Proteobacteria. Higher diversity of denitrifiers was observed in re
      vegetated forest soils than natural ones. Not only the community but also the
      abundance showed significant differences between forest types as well as depths.
      The abundance of denitrifiers ranged from 105 to 107 gene copies g-1 dry soil in
      this study. For nirK gene, the abundance was much higher in the lower layer than
      surface layer in both forest types, and the differences between winter and summer
      in natural forest soils were higher than those in re-vegetated forest soils. The
      abundance of nosZ and nirK genes showed a similar trend in natural forest, but
      the former was higher in matured forest than re-vegetated forest. This study
      provided a direct comparison on community composition and abundance of
      denitrifying bacteria in natural and re-vegetated acidic forest soils to allow
      further assessment of the nitrogen cycling.

PMID- 28500916
TI  - Valuing urban open space using the travel-cost method and the implications of
      measurement error.
AB  - Urbanization has placed pressure on open space within and adjacent to cities. In
      recent decades, a greater awareness has developed to the fact that individuals
      derive multiple benefits from urban open space. Given the location, there is
      often a high opportunity cost to preserving urban open space, thus it is
      important for both public and private stakeholders to justify such investments.
      The goals of this study are twofold. First, we use detailed surveys and precise,
      accessible, mapping methods to demonstrate how travel-cost methods can be applied
      to the valuation of urban open space. Second, we assess the degree to which
      typical methods of estimating travel times, and thus travel costs, introduce bias
      to the estimates of welfare. The site we study is Taylor Mountain Regional Park,
      a 1100-acre space located immediately adjacent to Santa Rosa, California, which
      is the largest city (~170,000 population) in Sonoma County and lies 50 miles
      north of San Francisco. We estimate that the average per trip access value
      (consumer surplus) is $13.70. We also demonstrate that typical methods of
      measuring travel costs significantly understate these welfare measures. Our study
      provides policy-relevant results and highlights the sensitivity of urban open
      space travel-cost studies to bias stemming from travel-cost measurement error.

PMID- 28500913
TI  - MYB fusions and CD markers as tools for authentication and purification of cancer
      stem cells from salivary adenoid cystic carcinoma.
AB  - Cancer stem cells (CSC) are considered the major cause of aggressive tumor
      behavior, recurrence, metastases, and resistance to radiation, making them an
      attractive therapeutic target. However, isolation of CSC from tumor tissue and
      their characterization are challenging due to uncertainty about their molecular
      markers and conditions for their propagation. Adenoid cystic carcinoma (ACC),
      which arises predominantly in the salivary glands, is a slow-growing but
      relentless tumor that frequently invades nerves and metastasizes. New effective
      treatment approaches for ACC have not emerged over the last 40years. Previously,
      based on a highly conserved SOX10 gene signature that we identified in the
      majority of ACC tumors, we suggested the existence in ACC of SOX10+ cells with
      neural stem properties and corroborated this hypothesis via isolation from ACC
      tissue a novel population of CSC, termed ACC-CSC. These cells activated NOTCH1
      signaling and co-expressed SOX10 and other ACC-intrinsic neural crest stem cell
      markers with CD133, a CSC cell surface marker, suggesting that ACC is driven by a
      previously uncharacterized population of SOX10+/CD133+ cells with neural stem
      cell properties. Here, we authenticated ACC identity of our primary cultures by
      demonstrating that most of them harbor MYB-NFIB fusions, which are found in 86%
      of ACC. We demonstrated using CyTOF, a novel mass cytometry technology, that
      these cells express high beta-catenin and STAT3 levels and are marked by CD24 and
      CD44. Finally, to streamline development of ACC cell lines, we developed RT-PCR
      tests for distinguishing mouse and human cells and used immunomagnetic cell
      sorting to eliminate mouse cells from long-term cell cultures. Overall, this
      study describes a new population of CSC that activates signaling pathways
      associated with poor prognosis, validates their ACC identity, and optimizes
      approaches that can be used for purification of ACC-CSC and generation of cell
      lines.

PMID- 28500917
TI  - Using rapid-scan EPR to improve the detection limit of quantitative EPR by more
      than one order of magnitude.
AB  - X-band rapid-scan EPR was implemented on a commercially available Bruker ELEXSYS
      E580 spectrometer. Room temperature rapid-scan and continuous-wave EPR spectra
      were recorded for amorphous silicon powder samples. By comparing the resulting
      signal intensities the feasibility of performing quantitative rapid-scan EPR is
      demonstrated. For different hydrogenated amorphous silicon samples, rapid-scan
      EPR results in signal-to-noise improvements by factors between 10 and 50. Rapid
      scan EPR is thus capable of improving the detection limit of quantitative EPR by
      at least one order of magnitude. In addition, we provide a recipe for setting up
      and calibrating a conventional pulsed and continuous-wave EPR spectrometer for
      rapid-scan EPR.

PMID- 28500918
TI  - Experience using high-dose glucose-insulin-potassium (GIK) in critically ill
      patients.
AB  - PURPOSE: To audit the use of GIK in terms of safety, haemodynamic effects, and
      impact on catecholamine dosage. MATERIALS AND METHODS: A retrospective,
      descriptive, evaluative audit of GIK use within the adult ICU of a London
      teaching hospital was conducted. Rescue therapy of GIK (up to
      1.0Unitsinsulin/kg/h) was administered to improve cardiac function. Outcomes were
      ICU survival, change in cardiac index (CI) and blood lactate levels, events of
      hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and
      discontinuation time of catecholamine inotropes. RESULTS: Of 85 patients treated
      with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home.
      In patients surviving until 72h, a trend of improved CI and lactate levels was
      seen, often with reductions in catecholamine dosing. Inotropes were discontinued
      in 35 (54%) patients. Severe hypoglycaemia (<2mmol/l), hyperglycaemia
      (>20mmol/l), hypokalaemia (<2.5mmol/l) and hyperkalaemia (>7mmol/l) during GIK
      affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly
      identified. No measurable harm was noted. CONCLUSIONS: High-dose GIK can be
      safely used in critically ill patients, though blood glucose and potassium levels
      must be monitored frequently. GIK was associated with improved CI and blood
      lactate levels. Impact on survival requires prospective evaluation.

PMID- 28500919
TI  - Kinetics of circulating fetuin-A may predict mortality independently from
      adiponectin, high molecular weight adiponectin and prognostic factors in
      critically ill patients with sepsis: A prospective study.
AB  - PURPOSE: Fetuin-A and adiponectin, major hepatokine and adipokine respectively,
      have been implicated in systematic inflammation. Our aim was to jointly
      investigate whether kinetics of circulating fetuin-A, adiponectin and its isoform
      HMWA predict 28-day mortality in sepsis. MATERIALS AND METHODS: In a prospective
      study, serum fetuin-A, adiponectin and HMWA were determined in 102 ICU patients
      fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after,
      and in 102 healthy controls matched on age and gender. RESULTS: Serum fetuin-A
      was significantly lower in septic patients than controls (p<0.001). Among septic
      patients, those with septic shock and nonsurvivors presented lower fetuin-A, but
      higher adiponectin and HMWA compared to patients with sepsis and survivors
      respectively, both at baseline and day 7 (p<0.001). Fetuin-A exhibited negative
      correlations with APACHE II, CRP, procalcitonin, adiponectin and IL-6 but a
      positive one with albumin. Reduced fetuin-A as well as lower serum kinetics of
      fetuin-A (HR: 0.55, 95% C.I. 0.34-0.91, p=0.02), adiponectin but not HMWA were
      independently associated with 28-day mortality adjusting for age, gender, BMI,
      APACHE II, septic shock and laboratory biomarkers. CONCLUSIONS: Circulating
      fetuin-A kinetics may be a prognostic biomarker in septic patients. More research
      is essential to elucidate fetuin-A's ontological role in sepsis pathophysiology.

PMID- 28500920
TI  - The impact of delayed rapid response call activation on patient outcomes.
AB  - PURPOSE: To investigate the impact of delay in rapid response call (RRC)
      activation on Hospital mortality. MATERIALS AND METHODS: This study was conducted
      in a university affiliated hospital providing medical, surgical, mental health,
      maternity, and pediatric services. RRCs were considered delayed if RRC activation
      was delayed by >=15min. The primary outcome measure was in-hospital mortality.
      Secondary outcomes included hospital length of stay (LOS), requirement of ICU
      admission, as well as requirement of mechanical ventilation and ICU LOS for
      patients requiring ICU admission. RESULTS: A total of 826 RRCs occurred in 629
      patient admissions. A quarter of all RRCs were delayed by >=15min, with a median
      delay of 1h and 20min. Patients with a delayed RRC had significantly higher in
      hospital mortality (34.7% vs. 21.2%; p=0.001,) and significantly longer
      hospitalizations (11.6 vs. 8.4days; p=0.036). After adjusting for confounders,
      RRC activation was independently associated with increased in-hospital mortality
      (OR=1.79; 95% CI=1.17-2.72: p=0.007). CONCLUSIONS: A delay of >=15min was
      associated with significantly increased in-hospital mortality and longer
      hospitalization. The factors contributing to the observed increase in mortality
      with delayed RRCs require further exploration.

PMID- 28500921
TI  - Development and validation of two measures of emotional contrast avoidance: The
      contrast avoidance questionnaires.
AB  - The Contrast Avoidance (CA) model (Newman & Llera, 2011) proposed that
      individuals with generalized anxiety disorder (GAD) fear sharp emotional shifts
      (or contrasts), such as the shift from a pleasant or neutral state to one of
      sudden distress following a negative event. Further, the model suggests that
      chronic worry is employed by those with GAD to sustain negative emotionality as a
      means to avoid sudden shifts into negativity. The model has received empirical
      support; however, no validated measure exists to assess CA tendencies. In this
      paper we developed and tested two measures of CA: one focusing on worry, and
      another examining broader mechanisms of CA that could be used test whether CA is
      applicable to other disorders. In Study 1, Part 1, we used 3 samples of
      participants (each N=410) to perform item reduction, exploratory factor analysis,
      and confirmatory factor analysis. In Study 1, Part 2, we performed tests of
      construct validity. In Study 2, we used a new sample (N=126) to determine test
      retest reliability. All data point to the strong psychometric properties of the
      CA questionnaires and their relationship to GAD. Both measures distinguished
      between participants reporting clinical levels of GAD symptoms and nonanxious
      controls, demonstrating their utility as complementary measures of CA tendencies.

PMID- 28500923
TI  - History, injury, and psychosocial risk factor commonalities among cases of fatal
      and near-fatal physical child abuse.
AB  - Failure to recognize child maltreatment results in chronic exposure to high-risk
      environments where re-injury or death may occur. We analyzed a series (n=20) of
      fatal (n=10) and near-fatal (n=10) physical child abuse cases from the
      Commonwealth of Kentucky to identify commonalities and determine whether
      indicators of maltreatment were present prior to the child's fatal or near-fatal
      event. We conducted retrospective state record reviews involving children <4years
      of age classified as physical child abuse by the Cabinet for Health and Family
      Services during a 12 month period. Cases were distributed across 17 counties. IRB
      approvals were obtained. Three reviewers concurrently abstracted case data from
      medical, social, and legal documents, and descriptive statistics were analyzed.
      Median age of subjects was 7.5 months (range 1-32 months); 55% were male.
      Psychosocial risk factors (PRFs) were present in 100% of cases. Traumatic brain
      injury (95%) and bruising (90%) were the most common injuries. Of the 14 children
      with available prior medical records, 9 (64%) had sentinel injuries in the form
      of prior unexplained bruising; all nine suffered subsequent traumatic brain
      injury resulting in four deaths. A male was caring for the child at the time of
      the final event in 70% of cases. Our study identified key commonalities across
      cases of fatal and near-fatal abuse, highlighting the prevalence of psychosocial
      risk factors and the significance of prior unexplained bruising as a herald of
      escalating abuse. Further study is warranted to ascertain the predictive value of
      our findings in the larger population.

PMID- 28500922
TI  - Adverse childhood experiences and suicide attempts among those with mental and
      substance use disorders.
AB  - Using the 2012-2013 National Epidemiologic Survey on Alcohol and Related
      Conditions data, we examined the associations of ten types of adverse childhood
      experiences (ACEs) with (1) lifetime suicide attempts and (2) number and age of
      attempts among U.S. adults aged 18+. In a case-control design, suicide attempters
      (5.14% of the full sample) were matched with never attempters (matched sample
      N=3912) on nine mental and substance use disorders. ACE rates were higher among
      attempters (3.30 [SE=0.07]) than their matched controls (2.19 [SE=0.06]). Results
      from multivariable logistic regression analyses showed that sexual abuse and
      parental/other family member's mental illness were associated with increased odds
      of having attempted suicide among both genders, and emotional neglect was also a
      factor for men. Population attributable risk fractions for sexual abuse were
      25.75% for women and 8.56% for men. Sexual abuse and a higher number of ACEs were
      also related to repeated suicide attempts. A higher number of ACEs was associated
      with a younger first attempt age. Gay/bisexual orientation in men and the lack of
      college education in both genders were significant covariates. In conclusion,
      this study underscores that ACEs are significantly associated with lifetime
      suicide attempts even when mental and substance use disorders are controlled.

PMID- 28500925
TI  - Revisiting racial disparities in access to surgical management of drug-resistant
      temporal lobe epilepsy post implementation of Affordable Care Act.
AB  - OBJECTIVES: Prior to enactment of the Affordable Care Act(ACA), several reports
      demonstrated remarkable racial disparities in access to surgical care for
      epileptic patients. Implementation of ACA provided healthcare access to 7-16
      million uninsured Americans. The current study investigates racial disparity post
      ACA era in (1) access to surgical management of drug-resistant temporal lobe
      epilepsy (DRTLE); (2) short-term outcomes in the surgical cohort. PATIENT AND
      METHODS: Adult patients with DRTLE registered in the National Inpatient Sample
      (2012-2013) were identified. Association of race (African Americans and other
      minorities with respect to Caucasians) with access to surgical management of TLE,
      and short-term outcomes [discharge disposition, length of stay (LOS) and hospital
      charges] in the surgical cohort were investigated using multivariable regression
      techniques. RESULTS: Of the 4062 patients with DRTLE, 3.6%(n=148) underwent
      lobectomy. Overall, the mean age of the cohort was 42.35+/-16.33years, and 54%
      were female. Regression models adjusted for patient demographics, clinical and
      hospital characteristics demonstrated no racial disparities in access to surgical
      care for DRTLE. Likewise, no racial disparity was noted in outcomes in the
      surgical cohort. CONCLUSION: Our study reflects no racial disparity in access to
      surgical care in patients with DRTLE post 2010 amendment of the ACA. The seismic
      changes to the US healthcare system may plausibly have accounted for addressing
      the gap in racial disparity for epilepsy surgery.

PMID- 28500924
TI  - Caregiver parenting and gender attitudes: Associations with violence against
      adolescent girls in South Kivu, Democratic Republic of Congo.
AB  - Violence against adolescent girls occurs at alarmingly high rates in conflict
      affected settings, in part due to their increased vulnerability from their age
      and gender. However, humanitarian programming efforts have historically focused
      either on child abuse prevention or intimate partner violence prevention and have
      not fully addressed the specific needs of adolescent girls, including engagement
      of caregivers to reduce risk of violence against adolescent girls. Thus, the
      objectives of this analysis are to examine the whether gendered and parental
      attitudes of caregivers in South Kivu, Democratic Republic of Congo (DRC) were
      associated with their adolescent girls' experiences of violence and girls'
      attitudes towards IPV. Cross-sectional data from 869 girls (10-14 years) and
      their caregivers (n=764) were drawn from a baseline assessment of a violence
      prevention evaluation conducted in 2015. Findings suggest that female caregiver's
      gender equitable attitudes for adults may be associated with reduced odds of
      sexual abuse and less acceptance of IPV for adolescent girl children. Parenting
      attitudes and beliefs and gender equity for girl children were not associated
      with violence risk for girls, while increased accepting attitudes of negative
      discipline were only associated with lowered odds of sexual abuse. Understanding
      of caregivers' attitudes may provide potential insight into how to more
      effectively engage and develop programming for caregivers to promote the safety
      and well-being of adolescent girls.

PMID- 28500926
TI  - Different patterns of gelatinolytic activity in pituitary macro- and
      microadenomas.
AB  - OBJECTIVE: Gelatinases, Matrix MetalloProteinase(MMP)-2 and MMP-9, belong to zinc
      dependent endopeptidases involved in several physiological and pathological
      processes including inflammation and tumor development. Because the information
      about the involvement of gelatinases in pituitary adenoma (PA) development are
      scant, our objective was the analysis of MMP-2 and MMP-9 activity in serum and
      tumor tissue of PA patients. PATIENTS AND METHODS: Twenty one patients with PA
      (macroadenoma n=18, microadenoma n=3), qualified to the endoscopic resection of
      tumors were enrolled. Venous blood samples were collected before the surgery and
      PA tissue was collected during the surgery. Tissue material was homogenized in a
      buffer containing 0.1M Tris-HCl pH 7.4 and centrifuged. The supernatant was set
      to the equal protein content 18MUg/sample. Protein level in tissue samples was
      estimated with Bradford method. MMP-2 and MMP-9 analysis in serum and tissue was
      performed with gelatin zymography. RESULTS: The proteolytically activated forms
      of MMPs were not observed in the analyzed sera. Serum activities of MMP-2 and MMP
      9 did not statistically differ between patients with micro and macroadenomas. The
      analysis of material obtained from tissue of microadenomas showed slightly lower
      activities of both forms of MMP-9 (pro-MMP-9 and MMP-9/lipokalin heterodimer).
      Simultaneously the increased activity of pro-MMP-2 in comparison to macroadenomas
      was observed. Although differences observed did not reach statistical
      significance, only in the case of microadenomas the presence of the active form
      of MMP-2 (molecular weight 65kDa band) was observed. CONCLUSION: In the course of
      PA growth the change the biochemical profile of the gelatinolytic activity within
      the tumor tissue is observed. Initially, the higher activity of MMP-2 in
      microadenomas and elevated activity of MMP-9 in macroadenomas were detected.

PMID- 28500927
TI  - Comparison of electromagnetic neuronavigation system and free-hand method for
      ventricular catheter placement in internal shunt.
AB  - OBJECTIVE: Optimal ventricular catheter positioning is able to reduce the risk of
      catheter dysfunction, and subsequently the risk of multiple revision surgery. The
      objective of our study was to compare the proportion of optimal ventricular
      catheter placements in a cohort of patients operated for ventriculoperitoneal
      (VP) shunt between a free-hand group and a neuronavigated group. PATIENTS AND
      METHODS: Twenty patients with hydrocephalus requiring VP shunt were prospectively
      included in this study. Patients were divided into two groups; the ventricular
      catheter was positioned using free-hand method (n=10) or magnetic navigation
      system (n=10). For the two groups, clinical baseline characteristics, etiology of
      hydrocephaly and initial ventricular size were assessed. The main judgment
      criterion was the proportion of optimal catheter placements defined by the
      presence of all catheter holes in the ventricle, evaluated on post-operative CT
      scan. RESULTS: There was no initial difference between the two groups in terms of
      hydrocephalus etiology or initial ventricular size. The number of optimal
      catheter placements was 6/10 in the neuronavigated group versus 1/10 in the free
      hand group (p<0.05). There were no complications during post-operative period in
      either cohort. CONCLUSION: In patients suffering from hydrocephaly, the use of an
      electromagnetic neuronavigation system for ventricular catheter placement
      significantly improved the proportion of optimal catheter placements. Long-term
      follow-up is necessary to evaluate the number of revision surgeries and the cost
      in each group.

PMID- 28500928
TI  - Molecular cloning, characterization and in silico analysis of a thermostable beta
      glucosidase enzyme from Putranjiva roxburghii with a significant activity for
      cellobiose.
AB  - The native Putranjiva roxburghii family 1 glycoside hydrolase enzyme showed beta
      D-fucosidase activity in addition to beta-D-glucosidase and beta-D-galactosidase
      activities reported in our previous study. A single step concanvalin A affinity
      chromatography for native PRGH1 improved the yield and reduced the purification
      time. The PRGH1 gene was cloned and overexpressed in E. coli. The full length
      gene contained an ORF of 1617 bp encoding a polypeptide of 538 amino acids. The
      amino acid sequence of PRGH1 showed maximum similarities to beta-glucosidases and
      myrosinases. Both native and recombinant protein showed maximum hydrolytic
      activity for pNP-Fuc followed by pNP-Glc and pNP-Gal. Significant enzyme activity
      was also observed for cellobiose, however it decreased with increase in chain
      length for glycan substrates. The enzyme showed significant resistant to D
      glucose concentration up to 500 mM. Mutational studies confirmed the predicted
      catalytic acid/base Glu173 and nucleophile Glu389 as key residues for its
      activity. Moreover, Glu446 and Asn172 played essential role in substrate binding
      by interacting with the -1 subsite of substrates. Bioinformatic analysis
      suggested the possible reasons for the broad substrate specificity and other
      properties of the enzyme. PRGH1 had high sequence similarity towards S
      glucosidase and may be involved in defence. The broad specificity, catalytic
      efficiency and thermostability make PRGH1 potentially an important industrial
      enzyme.

PMID- 28500929
TI  - Oleanane-type glycosides from Pittosporum tenuifolium "variegatum" and P.
      tenuifolium "gold star".
AB  - The phytochemical study of two cultivars of Pittosporum tenuifolium Banks & Sol.
      ex Gaertn, "variegatum" and "gold star", led to the isolation of eight oleanane
      type glycosides: seven previously undescribed and a known one. Their aglycons are
      oxygenated oleanane derivatives as barringtogenol C, camelliagenin A,
      hederagenin, and 22alpha-hydroxyoleanolic acid. Their structures were established
      by 2D NMR spectroscopic techniques and mass spectrometry as 3-O-beta-D
      galactopyranosyl-(1 -> 2)-[alpha-L-arabinopyranosyl-(1 -> 3)]-beta-D
      glucuronopyranosyl-21-O-angeloyl-22-O-acetylbarringtogenol C, 3-O-beta-D
      galactopyranosyl-(1 -> 2)-[alpha-L-arabinopyranosyl-(1 -> 3)]-beta-D
      glucuronopyranosyl-21,22-di-O-angeloylbarringtogenol C, 3-O-beta-D
      galactopyranosyl-(1 -> 2)-[alpha-L-arabinopyranosyl-(1 -> 3)]-beta-D
      glucuronopyranosyl-22-O-angeloylcamelliagenin A, 3-O-beta-D-glucopyranosyl-(1 ->
      2)-[beta-D-glucopyranosyl-(1 -> 6)]-beta-D-glucopyranosyl-22-O-[(6-O-acetyl)-beta
      D-glucopyranosyl]camelliagenin A, 3-O-beta-D-galactopyranosyl-(1 -> 2)-[alpha-L
      arabinofuranosyl-(1 -> 4)]-beta-D-glucuronopyranosylhederagenin 28-O-beta-D
      glucopyranosyl ester, 3-O-alpha-L-arabinofuranosyl-(1 -> 4)-beta-D
      glucuronopyranosylhederagenin 28-O-beta-D-glucopyranosyl ester, 3-O-beta-D
      galactopyranosyl-(1 -> 2)-[alpha-L-arabinofuranosyl-(1 -> 4)]-beta-D
      glucuronopyranosyl-22alpha-hydroxyoleanolic acid 28-O-beta-D-glucopyranosyl
      ester, and the known ilexoside XLIX. These results represent a significative
      contribution to the chemotaxonomy of the genus Pittosporum, highlighting
      hederagenin-type saponins as chemotaxonomic markers of P. tenuifolium cultivars.

PMID- 28500930
TI  - Micro-computed tomography, scanning electron microscopy and energy X-ray
      spectroscopy studies of facet joint degeneration: A comparison to clinical
      imaging.
AB  - Segmental degeneration in the human lumbar spine affects both the intervertebral
      discs and facet joints. Facet joint degeneration not only affects the cartilage
      surface, but also alters the cellular properties of the cartilage tissue and the
      structure of the subchondral bone. The primary focus of this study is the
      investigation of these microstructural changes that are caused by facet joint
      degeneration. Microstructural analyses of degenerated facet joint samples,
      obtained from patients following operative lumbar interbody fusion, have not
      previously been extensively investigated. This study analyzes human facet joint
      samples from the inferior articular process using scanning electron microscopy,
      micro-computed tomography, and energy dispersive X-ray spectroscopy to evaluate
      parameters of interest in facet joint degeneration such as elemental composition,
      cartilage layer thickness and cell density, calcification zone thickness,
      subchondral bone portion, and trabecular bone porosity. These microstructural
      analyses demonstrate fragmentation, cracking, and destruction of the cartilage
      layer, a thickened calcification zone, localized calcification areas, and cell
      cluster formation as pathological manifestations of facet joint degeneration. The
      detailed description of these microstructural changes is critical for a
      comprehensive understanding of the pathology of facet joint degeneration, as well
      as the subsequent development and efficacy analysis of regenerative treatment
      strategies.

PMID- 28500931
TI  - The influence of polycyclic aromatic hydrocarbons on lung function in a
      representative sample of the Canadian population.
AB  - We investigated the associations between exposure to polycyclic aromatic
      hydrocarbons (PAHs) and selected respiratory physiologic measures in cycles 2 and
      3 of the Canadian Health Measures Survey, a nationally representative population
      sample. Using generalized linear mixed models, we tested the association between
      selected PAH metabolites and 1-second forced expiratory volume (FEV1), forced
      vital capacity (FVC), and the ratio between the two (FEV1/FVC) in 3531 people
      from 6 to 79 years of age. An interquartile change in urinary PAH metabolite was
      associated with significant decrements in FEV1 and FVC for eight PAHs, 2
      hydroxynapthalene, 1-, and 2-hydroxyphenanthrene, 2-, 3-, and 9-hydroxyfluorene
      and 3- and 4-hydroxyphenanthrene. Exposure to PAH may negatively affect lung
      function in the Canadian population.

PMID- 28500933
TI  - Functional consequences of inhibitory plasticity: homeostasis, the excitation
      inhibition balance and beyond.
AB  - Computational neuroscience has a long-standing tradition of investigating the
      consequences of excitatory synaptic plasticity. In contrast, the functions of
      inhibitory plasticity are still largely nebulous, particularly given the
      bewildering diversity of interneurons in the brain. Here, we review recent
      computational advances that provide first suggestions for the functional roles of
      inhibitory plasticity, such as a maintenance of the excitation-inhibition
      balance, a stabilization of recurrent network dynamics and a decorrelation of
      sensory responses. The field is still in its infancy, but given the existing body
      of theory for excitatory plasticity, it is likely to mature quickly and deliver
      important insights into the self-organization of inhibitory circuits in the
      brain.

PMID- 28500932
TI  - Mass spectral characterization of tabun-labeled lysine biomarkers in albumin.
AB  - Tabun has been shown to form phosphylated adducts on tyrosine residues in albumin
      in vivo and in vitro. However, in this work, tabun-labeled lysine adducts were
      found in albumin. Three types of albumin were treated with overdose of tabun in
      vitro and 17 tabun-labeled lysine residues were found: K4, K12, K224, K377, and
      K524 in bovine albumin, K186, K188, K212, K329, K414, and K525 in leporine
      albumin, and K79, K186, K188, K212, K376, and K525 in rat albumin. To investigate
      the modification of tabun in vivo, three leporines were injected with 0.8*LD50
      dose of tabun. The results showed that the labeled lysine residues in vivo, were
      consistent with modified lysines in vitro. Structure characteristics and the
      binding mode of 6 tabun-labeled lysines of leporine albumin were further analyzed
      using theory simulation and molecular docking in Discovery Studio. For the first
      time, we show that tabun-labeled lysine peptides are found in vivo and in vitro.
      These modified lysine peptides are good biomarkers for exposure to tabun in
      albumin of leporine and rat.

PMID- 28500934
TI  - Interactions of natural resins and pigments in works of art.
AB  - The degradation process involving the formation of metal soaps in drying oils is
      a well-known problem due to cations from pigments reacting with free fatty acids
      from the oil. The aggregation of these carboxylates in semi-crystalline
      structures can lead to eruptions through the paint layers and 'blooming' on the
      surface. In this work, the metal soaps formation in presence of natural resins
      has been assessed and studied by means of Fourier transform infrared spectroscopy
      with experiments concerning the ageing of drying oil and different natural resins
      (shellac, dammar and colophony) in the presence of common historic pigments
      (smalt, ochre, umber, azurite, lead white, zinc white and titanium white).
      Mixtures of resins and pigments have been exposed to photo-ageing in solar box up
      to 1000h, thermal ageing at 50 degrees C up to 1100h and 6month of room
      conditions exposure as reference. The decrease in the intensity of the carbonyl
      band in the spectra, as well as the contemporary increase of the metal
      carboxylates (in the range from 1500 to 1650cm-1) absorption bands, were used as
      the main indicators of metal soap formation. It has been observed that some
      pigments, particularly zinc white and smalt, present a 'catalytic' effect
      favouring the simultaneous formation of associated oxalates. The formation of
      oxalates and different degradation products from natural resins in the presence
      of pigments is particularly important, as it deeply affects the removability of
      varnishes and, more generally, the cleaning processes. Moreover, it permanently
      modifies the interface between painting and varnish layers as well as the
      aesthetic aspects of the painted surfaces. The influence of natural resins
      reactivity with pigments and their role in the oxalate formation is an issue
      still unexplored.

PMID- 28500935
TI  - Enhanced pseudocapacitive performance of electroactive p-type conductive polymer
      in the presence of 1-octadecyl-3-methylimidazolium bromide.
AB  - In present work, for improving the electrochemical performance of conductive
      polymer, POAP/1-octadecyl-3-methylimidazolium Bromide ([OMD]Br) composite films
      have been fabricated by POAP electropolymerization in the presence of [OMD]Br as
      active electrodes for electrochemical supercapacitors. Different electrochemical
      methods including galvanostatic charge discharge experiments, cyclic voltammetry
      and electrochemical impedance spectroscopy have been applied to study the system
      performance. Analyses of DFT results show that the atomic-scale electronic
      properties are generally depend on the bonding and electronic molecular
      structures (and thus their variation with the external bias in real nano
      electrochemical circuits). The supercapacity behavior of the composite film was
      attributed to the (i) high active surface area of the composite, (ii) charge
      transfer along the polymer chain due to the conjugation form of the polymer and
      finally (iii) synergism effect between conductive polymer and [OMD]Br.

PMID- 28500936
TI  - Facile hydrothermal synthesis of urchin-like cobalt manganese spinel for high
      performance supercapacitor applications.
AB  - A facile hydrothermal method has been adopted to synthesize the spherical urchin
      like hierarchical CoMn2O4 nanostructures on the nickel foam substrate. The as
      synthesized urchins have an average diameter of ~3-7MUm with numerous self
      assembled nanoneedles grown radically in all the directions from its center with
      a huge void space between them. For comparison, we have also studied the
      electrochemical as well as other physicochemical properties of parent simple
      Co3O4 and MnO2 materials, which were also synthesized by a similar hydrothermal
      method. The results show that CoMn2O4 electrode displayed significantly higher
      (more than two times) areal and specific capacitances compared to Co3O4 and MnO2
      electrodes with excellent capacitance retention and Coulombic efficiency.
      Moreover, the energy and power densities obtained for CoMn2O4 electrode are also
      far higher than the parent Co3O4 and MnO2. Long-term cycling tests of CoMn2O4
      electrode shows the improved capacitance with high rate capability up to 6000
      cycles indicating their potential for high performance supercapacitor
      applications. The better electrochemical performance of CoMn2O4 electrode can be
      attributed to the smart urchin-like nanostructures, which has several advantages
      like, more electroactive sites for faradic reactions emerging from the two metal
      ions, higher electronic/ionic conductivity and fast electrolyte transportation
      kinetics promoted by unique morphology.

PMID- 28500937
TI  - Computational methodology for determining textural properties of simulated porous
      carbons.
AB  - We have refined and improved the computational efficiency of the TriPOD
      technique, used to determine the accessible characteristics of porous solids with
      a known configuration of solid atoms. Instead of placing a probe molecule
      randomly, as described in the original version of the TriPOD method (Herrera et
      al., 2011), we implemented a scheme for dividing the porous solid into 3D-grids
      and computing the solid-fluid potential energies at these grid points. We
      illustrate the potential of this technique in determining the total pore volume,
      the surface area and the pore size distribution of various molecular models of
      porous carbons, ranging from simple pore models to a more complex simulated
      porous carbon model; the latter is constructed from a canonical Monte Carlo
      simulation of carbon microcrystallites of various sizes.

PMID- 28500938
TI  - Importance of crystallinity of anchoring block of semi-solid amphiphilic triblock
      copolymers in stabilization of silicone nanoemulsions.
AB  - Polymer emulsifiers solidified at the interface between oil and water can provide
      exceptional dispersion stability to emulsions due to the formation of unique semi
      solid interphase. Our recent works showed that the structural stability of
      paraffin-in-water emulsions highly depends on the oil wettability of hydrophobic
      block of methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-b
      PCL). Here we investigate the effects of the crystallinity of hydrophobic block
      of triblock copolymer-based emulsifiers, PCLL-b-PEG-b-PCLL, on the colloidal
      properties of silicone oil-in-water nanoemulsions. The increased ratio of l
      lactide to epsilon-caprolactone decreases the crystallinity of the hydrophobic
      block, which in turn reduces the droplet size of silicone oil nanoemulsions due
      to the increased chain mobility at the interface. All of the prepared
      nanoemulsions are very stable for a month at 37 degrees C. However, the exposure
      to repeated freeze-thaw cycles quickly destabilizes the nanoemulsions prepared
      using the polymer with the reduced crystallinity. This work demonstrates that the
      anchoring chain crystallization in the semi-solid interphase is critically
      important for the structural robustness of nanoemulsions under harsh physical
      stresses.

PMID- 28500939
TI  - Novel molecularly imprinted polymer based on beta-cyclodextrin@graphene oxide:
      Synthesis and application for selective diphenylamine determination.
AB  - A sensitive and selective molecularly imprinted polymer (MIP) for the
      determination of diphenylamine (DPA) was developed based on host-guest
      interactions of a cyclodextrin-based polymer which possesses an inherent affinity
      for the target. The proposed GO@MIP has been prepared using the graphene oxide
      (GO) sheets as surface of polymerization, DPA as target molecule, beta
      cyclodextrin (beta-CD) and acrylamide (AM) as functional monomers,
      azobisisobutyronitrile (AIBN) as initiator and N, N methylene bisacrylamide
      (MBAm) as crosslinker which denoted as GO@MIP nanocomposite. The MIP sites were
      formed by the inclusion complex through interaction of DPA and beta-CD, followed
      by extraction of target. The resulting GO@MIP nanocomposite possess a fast
      adsorption kinetics, highly improved imprinting effect, high adsorption capacity,
      and it can be applied to fast extraction of DPA. The resultant GO@MIP
      nanocomposite was characterized using the Fourier transform infrared spectroscopy
      (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) scanning
      electron microscope (SEM) and energy-dispersive spectroscopy (EDS) analysis. On
      the other hand, the non-imprinted polymer (GO@NIP nanocomposite) has been
      synthesized and was used in the adsorption experiments. The MIP exhibited good
      affinity with a maximum adsorption capacity of 95.98mgg-1 and excellent
      selectivity toward DPA than other structural analogues such as 2-amino
      benzophenone and dithizone.

PMID- 28500940
TI  - Efficient catalytic hydration of cyanamides in aqueous medium and in the presence
      of Naringin sulfuric acid or green synthesized silver nanoparticles by using
      Gongronema latifolium leaf extract.
AB  - In this paper, a novel, efficient and green method for the preparation of
      Naringin sulfuric acid (NSA) as a Bronsted acid organocatalyst and silver
      nanoparticles (Ag NPs) by using Gongronema latifolium leaf extract as a reducing
      and stabilizing agent is introduced. The catalysts were characterized using the
      powder XRD, SEM, EDS, TEM, UV-Vis and FT-IR spectroscopy. Afterward, the
      catalytic activity of synthesized NSA and Ag NPs were investigated for the
      synthesis of N-monosubstituted ureas via the hydration of cyanamides in aqueous
      medium. All products were obtained in good to excellent yields. These methods
      provided several advantages such as shorter reaction time, simpler work-up and
      higher yield.

PMID- 28500941
TI  - Direct exfoliation of graphite in water with addition of ammonia solution.
AB  - To bring graphene closer to its real-world applications, finding a green, low
      cost, environment-friendly and less toxic solvent for production of high-quality
      graphene is highly demanded. However, water, the most widely used green solvent,
      is generally considered to be a poor solvent for hydrophobic graphene. In this
      study, we exfoliate graphene nanosheets directly in basic water without
      surfactants, polymers or organic solvents. The addition of a small amount of
      ammonia solution achieves the exfoliation of few-layer graphene nanosheets from
      pristine graphite. Diverse characterization methods are employed to investigate
      the morphology and quality of as-prepared graphene sheets. The release of gaseous
      ammonia plays the key role in exfoliation of graphene. The concentration of
      stable graphene dispersions can reach 0.058mg/mL.

PMID- 28500942
TI  - Synthesis of high surface area mesoporous MnO2 via a "metastable" aqueous
      interfacial reaction.
AB  - In this work, a metastable aqueous interface was fabricated for synthesizing
      mesoporous and high surface area MnO2. When urea was used as the additive,
      hierarchical spheres self-organized from ultrathin nano-sheets were obtained. Its
      porous structure could be controlled through adjusting the urea concentration,
      and a maximum surface area of 407m2 g-1 was achieved by this method, which is
      larger than the reported values. Due to the porous structure and high surface
      area, as-prepared MnO2 exhibited a specific capacitance of 775.4 F g-1 at a
      current density of 0.1 A g-1, and exhibited a 63.5% capacitance retention when
      the current density was increased from 0.1 A g-1 to 5A g-1. Durability studies
      showed a 63.7% capacitance retention after 2500 cycles. The metastable
      interfacial reaction approach could also be extended to other alloys with large
      surface area and porous structure, such as CoB alloy. This method provides a
      simple and low-cost method to synthesize high surface area and mesoporous
      materials.

PMID- 28500943
TI  - Quantitative interpretation of PAMAM dendrimers adsorption on silica surface.
AB  - Understanding the dendrimer-solid support interaction is of great importance for
      dendrimer-based drug delivery system design. The maximum surface coverage on a
      hydrophilic silica surface was determined using the quartz crystal microbalance
      with dissipation monitoring (QCM-D) and multi-parametric surface plasmon
      resonance (MP-SPR) methods: the adsorption process depends on ionic strength and
      pH of solutions. The effectiveness of G6 adsorption is mainly determined by the
      range of electrostatic inter-dendrimer interactions and dendrimer-silica surface
      interactions. Changes in ionic strength have a strong effect on the binding
      affinity of dendrimers to the surface. The trends in the binding affinity and the
      surface saturation amount correspond well with the degree of change of
      protonation of the adsorbed molecules. The development of new research techniques
      makes it possible to attain a more profound understanding of the self-assembling
      behaviour of dendrimers. The comparison of QCM-D and MP-SPR allowed the
      estimation that the dendrimer film contains approximately 70% water. These
      results indicate that 6th generation PAMAM dendrimers form very hydrated films on
      silica surfaces. In this case the number of water molecules associated per
      dendrimer molecule varied from 10,450 to 9,200. The hydration of dendrimer films
      seems to be a crucial aspect of their implementation. This data confirmed that
      dendrimers are very promising candidates for many biological applications.

PMID- 28500944
TI  - The structure evolution of colloidal aggregates composed of monodisperse silica
      nanospheres.
AB  - In this work, colloidal aggregates, such as higher-order clusters with polyhedral
      geometry, supraparticles with intermediate packing ordering, different inner
      structured supraballs with face-centered cubic ordering were produced through
      self-assembly of different quantities of monodisperse silica nanospheres in water
      in-oil emulsion droplets which were formed by ultrasonic dispersion of silica
      nanospheres suspension into different solvents. The structure evolution of
      colloidal aggregates as a function of the number of constituent silica
      nanospheres was studied in this article. It was found that the inner structures
      of colloidal aggregates would be changed with increasing of the number of
      constituent silica nanospheres in different solvents. In the case of n-octanol
      being as solvent, the supraparticles were the transition structure for higher
      order clusters into supraballs with hollow structure, while in silicone oil, the
      supraparticles were the transition structure for higher-order clusters into solid
      structured supraballs.

PMID- 28500945
TI  - Carbohydrate-based electrochemical biosensor for detection of a cancer biomarker
      in human plasma.
AB  - Autocrine motility factor (AMF) is a tumor-secreted cytokine that stimulates
      tumor cell motility in vitro and metastasis in vivo. AMF could be detected in
      serum or urine of cancer patients with worse prognosis. Reported as a cancer
      biomarker, AMF secretion into body fluids might be closely related to metastases
      formation. In this study, a sensitive and specific carbohydrate-based
      electrochemical biosensor was designed for the detection and quantification of a
      protein model of AMF, namely phosphoglucose isomerase from rabbit muscle (RmPGI).
      Indeed, RmPGI displays high homology with AMF and has been shown to have AMF
      activity. The biosensor was constructed by covalent binding of the enzyme
      substrate d-fructose 6-phosphate (F6P). Immobilization was achieved on a gold
      surface electrode following a bottom-up approach through an aminated surface
      obtained by electrochemical patterning of ethylene diamine and terminal amine
      polyethylene glycol chain to prevent non-specific interactions. Carbohydrate
      protein interactions were quantified in a range of 10 fM to 100nM. Complex
      formation was analyzed through monitoring of the redox couple Fe2+/Fe3+ by
      electrochemical impedance spectroscopy and square wave voltammetry. The F6P
      biosensor demonstrates a detection limit of 6.6 fM and high selectivity when
      compared to other non-specific glycolytic proteins such as d-glucose-6-phosphate
      dehydrogenase. Detection of protein in spiked plasma was demonstrated and
      accuracy of 95% is obtained compared to result obtained in PBS (phosphate
      buffered saline). F6P-biosensor is a very promising proof of concept required for
      the design of a carbohydrate-based electrochemical biosensor using the enzyme
      substrate as bioreceptor. Such biosensor could be generalized to detect other
      protein biomarkers of interest.

PMID- 28500946
TI  - PA-Tb-Cu MOF as luminescent nanoenzyme for catalytic assay of hydrogen peroxide.
AB  - Metal organic frameworks (MOFs) with flexible structures and components have
      aroused great interest in designing functional materials. In this work, we
      designed and made a kind of PA-Tb-Cu MOF nanoenzyme capable of emitting
      fluorescence for the catalytic reaction of hydrogen peroxide (H2O2). Luminescent
      Tb3+, catalytic Cu2+ and bridging ligand were assembled and integrated into a
      single material nanoenzyme. This PA-Tb-Cu MOF nanoenzyme not only possessed
      excellent catalytic activity comparable to horseradish peroxidase but also can
      real-time fluorescently indicate the concentration of H2O2 as low as 0.2uM during
      catalysis. Luminescent PA-Tb-Cu MOF nanoenzyme did not need a common combined use
      of natural/artificial enzymes and chromogenic reactions for the quantification of
      H2O2 in widely-used enzyme-catalytic reactions. The present strategy assembled
      directly from functional ions/molecules provides a new way for the design and
      development of smart, multifunctional artificial enzymes for wide applications in
      biocatalysis, bioassays and nano-biomedicine.

PMID- 28500947
TI  - Electrochemical latent redox ratiometric probes for real-time tracking and
      quantification of endogenous hydrogen sulfide production in living cells.
AB  - Hydrogen sulfide (H2S) was discovered as a third gasotransmitter in biological
      systems and recent years have seen a growing interest to understand its
      physiological and pathological functions. However, one major limiting factor is
      the lack of robust sensors to quantitatively track its production in real-time.
      We described a facile electrochemical assay based on latent redox probe approach
      for highly specific and sensitive quantification in living cells. Two chemical
      probes, Azido Benzyl ferrocene carbamate (ABFC) and N-alkyl Azido Benzyl
      ferrocene carbamate (NABFC) composed of azide trigger group were designed. H2S
      molecules specifically triggered the release of reporters from probes and the
      current response was monitored using graphene oxide film modified electrode as
      transducer. The detection limits are 0.32uM (ABFC) and 0.076uM (NABFC) which are
      comparable to those of current sensitive methods. The probes are successful in
      the determination of H2S spiked in whole human blood, fetal bovine serum, and E.
      coli. The continuous monitoring and quantification of endogenous H2S production
      in E. coli were successfully accomplished. This work lays first step stone
      towards real-time electrochemical quantification of endogenous H2S in living
      cells, thus hold great promise in the analytical aspects of H2S.

PMID- 28500948
TI  - Using reduced graphene oxide-Ca:CdSe nanocomposite to enhance
      photoelectrochemical activity of gold nanoparticles functionalized tungsten oxide
      for highly sensitive prostate specific antigen detection.
AB  - An ultrasensitive sandwich-type photoelectrochemical (PEC) immunosensor was
      constructed for the detection of prostate specific antigen (PSA). In this work,
      Au-nanoparticle-loaded tungsten oxide (WO3-Au) hybrid composites was applied as
      PEC sensing platform, while Ca ions doped CdSe equipped on the conducting
      framework of reduced graphene oxide (rGO-Ca:CdSe) nanocomposites were employed as
      the signal amplification probe. As for WO3-Au, massive Au nanoparticles were
      formed on the surface of WO3 without any additional reducing agent, providing a
      novel nanocarriers for anchoring plenty of the primary antibodies due to the
      large specific surface area and good biocompatibility by chemical bonding between
      Au nanoparticles and -NH2 of antibodies. Besides, the incorporation of the rGO
      and the doping of Ca ions could improve the conductivity and hinder the
      recombination of electron-hole pairs of CdSe nanoparticles effectively, thereby
      enhancing the photocurrent conversion efficiency. Based on the sandwich
      immunoreaction, the primary antibody was immobilized onto WO3-Au substrate, after
      the formed rGO-Ca:CdSe labels were captured onto the electrode surface via the
      specific antibody-antigen interaction, the photocurrent intensity could be
      further enhanced due to the sensitization effect. Under the optimal conditions,
      the proposed PEC immunosensor shows a linear relationship between photocurrent
      variation and the logarithm of PSA concentration in the wide range of 5pgmL-1 to
      50ngmL-1 with a low detection limit of 2.6pgmL-1 (S/N=3). Moreover, it also
      presented good stability and acceptable specificity, indicating the potential
      applications in clinical diagnostics.

PMID- 28500949
TI  - Human health risks for Legionella and Mycobacterium avium complex (MAC) from
      potable and non-potable uses of roof-harvested rainwater.
AB  - A quantitative microbial risk assessment (QMRA) of opportunistic pathogens
      Legionella pneumophila (LP) and Mycobacterium avium complex (MAC) was undertaken
      for various uses of roof-harvested rainwater (RHRW) reported in Queensland,
      Australia to identify appropriate usages and guide risk management practices.
      Risks from inhalation of aerosols due to showering, swimming in pools topped up
      with RHRW, use of a garden hose, car washing, and toilet flushing with RHRW were
      considered for LP while both ingestion (drinking, produce consumption, and
      accidental ingestion from various activities) and inhalation risks were
      considered for MAC. The drinking water route of exposure presented the greatest
      risks due to cervical lymphadenitis and disseminated infection health endpoints
      for children and immune-compromised populations, respectively. It is therefore
      not recommended that these populations consume untreated rainwater. LP risks were
      up to 6 orders of magnitude higher than MAC risks for the inhalation route of
      exposure for all scenarios. Both inhalation and ingestion QMRA simulations
      support that while drinking, showering, and garden hosing with RHRW may present
      the highest risks, car washing and clothes washing could constitute appropriate
      uses of RHRW for all populations, and toilet flushing and consumption of lettuce
      irrigation with RHRW would be appropriate for non- immune-compromised
      populations.

PMID- 28500950
TI  - Determining the effect of cartridge case coatings on GSR using post-fire priming
      cup residue.
AB  - Ammunition is typically composed of a lead-based priming mixture which
      contributes to the characteristics most commonly used for the identification of
      gunshot residue (GSR). Due to the health risks often associated with lead, the
      use of lead-free primers in ammunitions is becoming more popular. Thus, the
      presence of GSR is becoming more difficult to discern based on the traditional
      means, i.e. the presence of lead (Pb), barium (Ba), and antimony (Sb). While
      research has been conducted on the differences between lead-based and lead-free
      muzzle discharge residue, few have researched other components of ammunition
      which may lead to other means of characterizing GSR. This research, therefore,
      covers that gap by focusing on the priming cup present in ammunition and the
      residue which may originate from it, that can contribute to muzzle discharge
      residue. In this study, a lead-based and a lead-free ammunition from four
      different manufacturers were chosen. The cartridges were fired using a Glock 17,
      9mm Parabellum, collected post-fire, and subsequently de-primed resulting in the
      removal of the anvil. The GSR present on the anvils and cups was analyzed using
      scanning electron microscopy coupled with energy dispersive x-ray spectrometry
      (SEM-EDX). The data was then processed using unit vector analysis for
      normalization and analyzed using principal component analysis (PCA) and linear
      discriminant analysis (LDA). This data was then used to determine the components
      of the cartridge case which contribute to GSR and develop a method of
      characterization between lead-free and lead-based ammunition. Such a method will
      improve the detection of GSR by strengthening the criteria of identification.

PMID- 28500951
TI  - Hydrogen peroxide induces cell proliferation and apoptosis in pulp of rats after
      dental bleaching in vivo: Effects of the dental bleaching in pulp.
AB  - OBJECTIVE: This study provides an in vivo evaluation of the inflammatory
      response, levels of cell proliferation and apoptosis, and the presence of
      necrosis after dental bleaching with two concentrations of hydrogen peroxide
      (H2O2). DESIGN: Wistar rats were divided into Control (placebo gel), BLUE (20%
      H2O2, 1*50min), and MAXX (35% H2O2, 3*15min) groups. At 2 and 30days, the rats
      were killed (n=10). The jaws were processed for histology analysis and PCNA and
      Caspase-3-cleaved immunohistochemistry, and data were submitted to the Mann
      Whitney or ANOVA test (P<0.05). RESULTS: At 2days, the MAXX group showed necrosis
      and the BLUE group revealed moderate inflammation on the occlusal third of the
      crown (P<0.05). At 30days, tertiary dentin had formed and there was an absence of
      inflammation. The level of cell proliferation was higher in the middle third of
      the BLUE group (P<0.05), and cervical of MAXX at 2days (P<0.05), decreasing at
      30days. The apoptosis was present at 2days, particularly in the cervical third of
      the crown in the bleached groups (P<0.05), with a decrease only at 30days in the
      BLUE group (P<0.05). CONCLUSIONS: The concentration of H2O2 influences effects on
      the pulp tissue, where a higher concentration of H2O2 can cause necrosis in the
      pulp and a prolonged effect within the apoptotic process; lower concentrations of
      H2O2 provide moderate inflammation, cell proliferation and apoptosis with a
      reduction of these processes over time.

PMID- 28500953
TI  - Induced not just right and incompleteness experiences in OCD patients and non
      clinical individuals: An in vivo study.
AB  - BACKGROUND AND OBJECTIVES: Research on incompleteness and not-just right
      experiences, (INC/NJREs) indicate that some OCD symptom dimensions are motivated
      by these experiences rather than by anxiety. Most published data are
      correlational, using non-clinical individuals. This study sought to examine
      INC/NJREs in vivo in non-clinical and OCD individuals. METHODS: Study 1: Ninety
      three undergraduates were randomly assigned to a INC/NJREs induction (n=44) or
      non-induction task (n=47). Scores on self-reports assessing INC, NJREs, OCD,
      Anxiety, and Depression were also recorded. Study 2: Twenty adults with OCD
      performed the induction task and completed the same questionnaire-packet as the
      non-clinical participants. RESULTS: Study 1: The induction-group scored higher on
      several DVs of the experimental task, as INC/NJREs and uncomfortable physical
      sensations predicted impulses/urges to do something. All the DVs correlated with
      INC, NJREs, and OCD symptoms. Anxiety was only related to suppressing
      difficulties of the most intense sensation. Study 2: Results were comparable to
      those found in non-clinical people. Induced INC/NJREs correlated with compulsions
      severity and were associated with ordering, washing, and hoarding symptoms. OCDs
      did not differ from non-clinical subjects in the number of induced INC/NJREs, but
      they were more disturbing, difficult to suppress, and instigated more urges to do
      in OCDs. LIMITATIONS: The small group of OCDs and the lack of a non-OCD clinical
      group kept us from drawing conclusions about the specificity of INC/NJREs to some
      OCD symptoms. CONCLUSIONS: Findings support the role of INC/NJREs as stimuli
      triggering urges and/impulses to do and their impact on OCD severity.

PMID- 28500952
TI  - Isolation and characterization of lymphoid enhancer factor-1-positive deciduous
      dental pulp stem-like cells after transfection with a piggyBac vector containing
      LEF1 promoter-driven selection markers.
AB  - OBJECTIVE: Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein
      that is expressed in pre-B and T cells. LEF1 is also an important member of the
      Wnt/beta-catenin signaling pathway that plays important roles in the self-renewal
      and differentiation of embryonic stem cells. We speculated that LEF1 might
      function in the stem cells from human exfoliated deciduous teeth (SHED). In this
      study, we attempted to isolate such LEF1-positive cells from human deciduous
      dental pulp cells (HDDPCs) by genetic engineering technology, using the human
      LEF1 promoter. DESIGN: A piggyBac transposon plasmid (pTA-LEN) was introduced
      into HDDPCs, using the Neon(r) transfection system. After G418 selection, the
      emerging colonies were assessed for EGFP-derived fluorescence by fluorescence
      microscopy. Reverse transcription polymerase chain reaction (RT-PCR) analysis was
      performed using RNA isolated from these colonies to examine stem cell-specific
      transcript expression. Osteoblastic or neuronal differentiation was induced by
      cultivating the LEF1-positive cells with differentiation-inducing medium.
      RESULTS: RT-PCR analysis confirmed the expression of several stem cell markers,
      including OCT3/4, SOX2, REX1, and NANOG, in LEF1-positive HDDPCs, which could be
      differentiated into osteoblasts and neuronal cells. CONCLUSIONS: The isolated
      LEF1-positive HDDPCs exhibited the properties of stem cells, suggesting that LEF1
      might serve as a marker for SHED.

PMID- 28500954
TI  - Finger forces in fastball baseball pitching.
AB  - Forces imparted by the fingers onto a baseball are the final, critical aspects
      for pitching, however these forces have not been quantified previously as no
      biomechanical technology was available. In this study, an instrumented baseball
      was developed for direct measurement of ball reaction force by individual fingers
      and used to provide fundamental information on the forces during a fastball
      pitch. A tri-axial force transducer with a cable having an easily-detachable
      connector were installed in an official baseball. Data were collected from 11
      pitchers who placed the fingertip of their index, middle, ring, or thumb on the
      transducer, and threw four-seam fastballs to a target cage from a flat mound. For
      the index and middle fingers, resultant ball reaction force exhibited a bimodal
      pattern with initial and second peaks at 38-39ms and 6-7ms before ball release,
      and their amplitudes were around 97N each. The ring finger and thumb produced
      single-peak forces of approximately 50 and 83N, respectively. Shear forces for
      the index and middle fingers formed distinct peak at 4-5ms before release, and
      the peaks summed to 102N; a kinetic source for backspin on the ball. An
      additional experiment with submaximal pitching effort showed a linear
      relationship of peak forces with ball velocity. The peak ball reaction force for
      fastballs exceeded 80% of maximum finger strength measured, suggesting that
      strengthening of the distal muscles is important both for enhancing performance
      and for avoiding injuries.

PMID- 28500955
TI  - Economic evaluation of nurse practitioner and clinical nurse specialist roles: A
      methodological review.
AB  - BACKGROUND: Advanced practice nurses (e.g., nurse practitioners and clinical
      nurse specialists) have been introduced internationally to increase access to
      high quality care and to tackle increasing health care expenditures. While
      randomised controlled trials and systematic reviews have demonstrated the
      effectiveness of nurse practitioner and clinical nurse specialist roles, their
      cost-effectiveness has been challenged. The poor quality of economic evaluations
      of these roles to date raises the question of whether current economic evaluation
      guidelines are adequate when examining their cost-effectiveness. OBJECTIVE: To
      examine whether current guidelines for economic evaluation are appropriate for
      economic evaluations of nurse practitioner and clinical nurse specialist roles.
      METHODS: Our methodological review was informed by a qualitative synthesis of
      four sources of information: 1) narrative review of literature reviews and
      discussion papers on economic evaluation of advanced practice nursing roles; 2)
      quality assessment of economic evaluations of nurse practitioner and clinical
      nurse specialist roles alongside randomised controlled trials; 3) review of
      guidelines for economic evaluation; and, 4) input from an expert panel. RESULTS:
      The narrative literature review revealed several challenges in economic
      evaluations of advanced practice nursing roles (e.g., complexity of the roles,
      variability in models and practice settings where the roles are implemented, and
      impact on outcomes that are difficult to measure). The quality assessment of
      economic evaluations of nurse practitioner and clinical nurse specialist roles
      alongside randomised controlled trials identified methodological limitations of
      these studies. When we applied the Guidelines for the Economic Evaluation of
      Health Technologies: Canada to the identified challenges and limitations,
      discussed those with experts and qualitatively synthesized all findings, we
      concluded that standard guidelines for economic evaluation are appropriate for
      economic evaluations of nurse practitioner and clinical nurse specialist roles
      and should be routinely followed. However, seven out of 15 current guideline
      sections (describing a decision problem, choosing type of economic evaluation,
      selecting comparators, determining the study perspective, estimating
      effectiveness, measuring and valuing health, and assessing resource use and
      costs) may require additional role-specific considerations to capture costs and
      effects of these roles. CONCLUSION: Current guidelines for economic evaluation
      should form the foundation for economic evaluations of nurse practitioner and
      clinical nurse specialist roles. The proposed role-specific considerations, which
      clarify application of standard guidelines sections to economic evaluation of
      nurse practitioner and clinical nurse specialist roles, may strengthen the
      quality and comprehensiveness of future economic evaluations of these roles.

PMID- 28500957
TI  - Design & synthesis of novel oxazolone & triazinone derivatives and their
      biological evaluation as COX-2 inhibitors.
AB  - A new series of oxazolones and triazinones were designed and synthesized and
      evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the
      new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass
      spectra. Most of the derivatives showed good inhibitory activity against COX-2
      enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024,
      0.019, 0.011 and 0.014uM compared to celecoxib as reference drug with IC50 value
      of 0.05uM. Altogether, these results indicate that these derivatives can be
      effective anti-inflammatory agents.

PMID- 28500956
TI  - Efficient synthesis of novel dialkyl-3-cyanopropylphosphate derivatives and
      evaluation of their anticholinesterase activity.
AB  - Based on the broad spectrum of biological activities associated with
      organophosphates, a novel type of this class of compounds was synthesized,
      bearing a nitrile group, from the sodium alkoxide-catalyzed reaction of
      dialkylphosphites with gamma-ketonitriles at 80 degrees C under solvent-free
      conditions. A reaction mechanism involving a phospha-Brook type rearrangement is
      proposed. Eight title compounds were investigated for their in vitro inhibitory
      potency and selectivity against acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) using Ellman's spectrophotometric method. The
      synthesized derivatives exhibited mostly a moderate activity against both
      cholinesterases. The IC50 values for BChE were in a smaller concentration range
      (5.96-23.35uM) compared to those for AChE inhibition (9.61-53.74uM). The diethyl
      3-cyano-1-p-tolylpropylphosphate which displayed the higher dual inhibitory
      potency towards both cholinesterases could be considered as a potential candidate
      for developing new drugs to treat Alzheimer's disease.

PMID- 28500958
TI  - Development of an updated normative data table for hand grip and pinch strength:
      A pilot study.
AB  - STUDY DESIGN: Pilot cross-sectional clinical measurement. INTRODUCTION: Normative
      tables for assessment of grip and pinch strength were developed 30 years ago and
      are likely outdated. PURPOSE OF STUDY: To assess suitability of current normative
      tables to evaluate hand and grip strength in clinical practice. METHODS: Hand
      grip strength (HGS) data were measured in 120 healthy subjects for comparison to
      normative values by gender, age, and handedness. RESULTS: Statistically
      significant differences in HGS measurements (grip, key pinch, and palmar pinch)
      between our measurements and normative data were detected in males and females
      regardless of handedness. When the population was stratified by five year age
      groups per Mathiowetz Rating Scale and compared to Mathiowetz normal values, 23
      out of 120 possible comparisons (19%) had associated p-values <0.10, suggesting
      moderate evidence of differences between study and reference values. In simulated
      10-year age groups, 23 out of 60 possible comparisons (38%) had relatively large
      differences between our measurements and Mathiowetz [20/23 (87%) were greater
      than 10% and 8 (35%) were greater that 15%]. Negative differences (N=19) were
      more frequent than positive differences (N=4), which indicates our patient
      population as a whole has decreased HGS compared to previous populations though
      we note this difference in HGS measurements is less in patients over 45 years of
      age. CONCLUSIONS: Normative hand strength values need to be further assessed in a
      larger study to update normative standards for use in clinical practice. LEVEL OF
      EVIDENCE: 2c.

PMID- 28500959
TI  - Biomechanical evaluation of implant-supported prosthesis with various tilting
      implant angles and bone types in atrophic maxilla: A finite element study.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study is to evaluate and compare
      bone stress that occurs as a result of using vertical implants with simultaneous
      sinus augmentation with bone stress generated from oblique implants without sinus
      augmentation in atrophic maxilla. METHODS: Six, three-dimensional (3D) finite
      element (FE) models of atrophic maxilla were generated with SolidWorks software.
      The maxilla models were varied for two different bone types. Models 2a, 2b and 2c
      represent maxilla models with D2 bone type. Models 3a, 3b and 3c represent
      maxilla models with D3 bone type. Five implants were embedded in each model with
      different configurations for vertical implant insertion with sinus augmentation:
      Model 2a/Model 3a, 30 degrees  tilted insertion; Model 2b/Model 3b and 45 degrees
      tilted insertion; Model 2c/Model 3c. A 150 N load was applied obliquely on the
      hybrid prosthesis. The maximum von Mises stress values were comparatively
      evaluated using color scales. RESULTS: The von Mises stress values predicted by
      the FE models were higher for all D3 bone models in both cortical and cancellous
      bone. For the vertical implant models, lower stress values were found in cortical
      bone. Tilting of the distal implants by 30 degrees  increased the stress in the
      cortical layer compared to vertical implant models. Tilting of the distal implant
      by 45 degrees  decreased the stress in the cortical bone compared to the 30
      degrees  models, but higher stress values were detected in the 45 degrees  models
      compared to the vertical implant models. CONCLUSIONS: Augmentation should be the
      first treatment option in atrophic maxilla in terms of biomechanics. Tilted
      posterior implants can create higher stress values than vertical posterior
      implants. During tilting implant planning, the use of a 45 degrees  tilted
      implant results in better biomechanical performance in peri-implant bone than 30
      degrees  tilted implant due to the decrease in cantilever length.

PMID- 28500960
TI  - Infrared reflectometry of skin: Analysis of backscattered light from different
      skin layers.
AB  - We have recently reported infrared spectroscopy of human skin in vivo using
      quantum cascade laser excitation and photoacoustic or photothermal detection for
      non-invasive glucose measurement . Here, we analyze the IR light diffusely
      reflected from skin layers for spectral contributions of glucose. Excitation of
      human skin by an external cavity tunable quantum cascade laser in the spectral
      region from 1000 to 1245cm-1, where glucose exhibits a fingerprint absorption,
      yields reflectance spectra with some contributions from glucose molecules. A
      simple three-layer model of skin was used to calculate the scattering intensities
      from the surface and from shallow and deeper layers using the Boltzmann radiation
      transfer equation. Backscattering of light at wavelengths around 10MUm from the
      living skin occurs mostly from the Stratum corneum top layers and the shallow
      layers of the living epidermis. The analysis of the polarization of the
      backscattered light confirms this calculation. Polarization is essentially
      unchanged; only a very small fraction (<3%) is depolarized at 90 degrees  with
      respect to the laser polarization set at 0 degrees . Based on these findings, we
      propose that the predominant part of the backscattered light is due to specular
      reflectance and to scattering from layers close to the surface. Diffusely
      reflected light from deeper layers undergoing one or more scattering processes
      would appear with significantly altered polarization. We thus conclude that a non
      invasive glucose measurement based on backscattering of IR light from skin would
      have the drawback that only shallow layers containing some glucose at
      concentrations only weakly related to blood glucose are monitored.

PMID- 28500961
TI  - Influence of polyethylene glycol on the phase transition of poly(butylene
      adipate) thin films: Polymorphic control.
AB  - Control of the polymorphic crystals formation of poly(butylene adipate) (PBA) is
      crucial to tailor its performance. In the present study, we investigated the
      effect of polyethylene glycol (PEG) with molecular weight of 400 on the
      polymorphic crystal of PBA thin films using x-ray diffraction (XRD), temperature
      dependent infrared-reflection absorbance spectroscopy (IRRAS) and two-dimensional
      correlation analysis (2DCOS). XRD and IRRAS results suggest that the PBA thin
      film tends to grow alpha-form crystal with addition of PEG at room temperature.
      Increasing the PEG contribution to 30wt%, the PBA thin film shows alpha-form
      crystal only. Temperature-dependent IRRAS spectra indicate that pure PBA thin
      film exhibited alpha/beta mixed crystal and the beta-to-alpha transition was
      observed during the heating process. After the incorporation of PEG, PEG not only
      inhibits the growth of beta crystal but also suppresses the beta-to-alpha
      transition during the heating process. In addition, we unexpectedly captured
      three different amorphous bands of CO stretching of pure PBA from the
      asynchronous 2D correlation spectrum. The band at 1740cm-1 corresponded to the
      amorphous phase of PBA at room temperature, whereas 1746 and 1760cm-1
      respectively arose from the amorphous phase of PBA melting from alpha-form
      crystal and beta-form crystal. This study demonstrated that the crystal form of
      PBA can be modified by blending with PEG, providing a new method to control the
      crystal modification and physical properties of polymorphic PBA in their blend
      system.

PMID- 28500962
TI  - The methylation levels of the H19 differentially methylated region in human
      umbilical cords reflect newborn parameters and changes by maternal environmental
      factors during early pregnancy.
AB  - H19 is a tumor-suppressor gene, and changes in the methylation of the H19
      differential methylation region (H19-DMR) are related to human health. However,
      little is known about the factors that regulate the methylation levels of H19
      DMR. Several recent studies have shown that maternal environmental factors during
      pregnancy, such as smoking, drinking, chemical exposure, and nutrient intake, can
      alter the methylation levels of several genes in fetal tissues. In this study, we
      examined the effects of maternal factors on changes in the methylation levels of
      H19-DMR in the human umbilical cord (UC), an extra-embryonic tissue. Participants
      from the Chiba study of Mother and Children's Health (C-MACH) were enrolled in
      this study. Genomic DNA was extracted from UC samples, and the methylation level
      of H19-DMR was evaluated by methylation-sensitive high resolution melting
      analysis. Individual maternal and paternal factors and clinical information for
      newborns at birth were examined using questionnaires prepared in the C-MACH
      study, a brief-type self-administered diet history questionnaire (BDHQ) during
      early pregnancy (gestational age of 12 weeks), and medical records. Univariate
      and multivariate logistic regression analyses indicated that reduced H19-DMR
      methylation (<50% methylation) in UC tissues was positively related to decreased
      head circumference in newborns [odds ratio (OR) =2.82; 95% confidence intervals
      (CI): 1.21-6.87; p=0.0183 and OR =2.51; 95% CI: 1.02-6.46; p=0.0499,
      respectively]. Moreover, multiple comparison test showed that H19-DMR methylation
      in UC tissues was significantly reduced in the low calorie group (intake of less
      than 1,000kcal/day; methylation level: 40.98%; 95% CI: 33.86-48.11) compared with
      that in the middle (1,000-1,999kcal/day; methylation level: 51.28%; 95% CI: 48.28
      54.27) and high (>=2,000kcal/day; methylation level: 52.16%; 95% CI: 44.81-59.51)
      calorie groups (p=0.0054 and 0.047, respectively). In the subpopulations with low
      to moderate calorie intake (<2,000kcal/day), reduced H19-DMR methylation in UC
      tissues was significantly related to serum homocysteine concentration (OR =0.520;
      95% CI: 0.285-0.875; p=0.019), maternal age (OR =1.22; 95% CI: 1.01-1.52;
      p=0.049), and serum folate levels (OR =0.917; 95% CI: 0.838-0.990; p=0.040).
      These data indicated that H19-DMR methylation levels in human UC tissues could be
      modulated by maternal factors during early pregnancy and may affect fetal and
      newborn growth.

PMID- 28500963
TI  - Sensory profiling of low sodium frankfurter containing garlic products: Adequacy
      of Polarized Projective Mapping compared with trained panel.

PMID- 28500964
TI  - Dietary linseed oil supplemented with organic selenium improved the fatty acid
      nutritional profile, muscular selenium deposition, water retention, and
      tenderness of fresh pork.
AB  - Cross-bred pigs were fed a control diet (with 0.3ppm sodium selenite and 1.5%
      soybean oil) or organic selenium diets (0.3ppm Se-Yeast with 1.5% soybean or
      linseed oil) to investigate nutrient supplement effects on meat quality and
      oxidative stability. The organic selenium diets increased muscular selenium
      content up to 54%, and linseed oil increased n-3 fatty acids two-fold while
      lowering the n-6/n-3 fatty acid ratio from 13.9 to 5.9 over the selenite control
      diet (P<0.05). Organic selenium yeast treatments with linseed oil reduced pork
      drip loss by 58-74% when compared with diets with soybean oil. Lightness of fresh
      pork was slightly less for organic selenium groups than inorganic (P<0.05), but
      redness was mostly similar. Lipid oxidation (TBARS) and protein oxidation
      (sulfhydryl) during meat storage (4 degrees C up to 6days) showed no appreciable
      difference (P>0.05) between diets, in agreement with the lack of notable
      difference in endogenous antioxidant enzyme activity between these meat groups.

PMID- 28500967
TI  - A systematic review on potential mechanisms of minocycline in kidney diseases.
AB  - Kidney diseases need specialized health care and still are a reason of death.
      There is a large body of evidence that indicates minocycline possesses some
      cytoprotective effects beside of antibacterial properties. In this review, we
      aimed to explain cytoprotective mechanisms and kidney protection of minocycline.
      In order to find the effects of minocycline on kidney diseases a systematic
      literature search was performed, according to the guidelines proposed at the
      PRISMA statement in the electronic databases, including: PubMed, Scopus, and Web
      of Science up to August 2016, using the term 'minocycline' combined either by
      'kidney' or 'renal' and published in English language. The following criteria
      were included: (1) studies that used minocycline in renal diseases; (2) full-text
      articles; (3) English language; (4) no limitation in publications with in-vivo or
      in-vitro and human or animal subjects. Our search provided a total of 1056
      articles which 1045 of them were discarded due to not meeting the inclusion
      criteria. It has been clear that several factors, including apoptosis, oxidative
      stress, mitochondrial dysfunction and inflammation have pivotal roles in the
      development and progression of kidney diseases. Minocycline protective properties
      are via several ways, including anti-apoptotic, free radical scavenging, anti
      inflammatory, effect on mitochondrial functions and inhibition of matrix
      metalloproteinase. This systematic review confirmed that minocycline could have
      significant effects on treatment of renal malfunctions. However, regarding any
      possible adverse effects of antibiotics, it appears that more investigation is
      still needed in this context.

PMID- 28500966
TI  - Synthesis of novel benzylidene analogues of betulinic acid as potent cytotoxic
      agents.
AB  - Different benzylidene derivatives (15a-o and 16a-o) of betulinic acid were
      designed and synthesized in an effort to develop potent anticancer agents. All
      the synthesized derivatives along with betulinic acid were evaluated for
      cytotoxicity against a panel of five different human cancer cell lines A-549
      (Lung), PC-3 (Prostate), HCT 116 (Colon), MCF-7 (Breast) and MIA PaCa-2
      (Pancreatic) using SRB assay. Pharmacological results showed that compounds 15b,
      15c, 15i, 15k, 16a-c and 16l were found to have promising cytotoxic profile
      against various cancer cell lines tested (IC50 1-2 MUM). Best results were
      observed for compound 16c with IC50 values 1.5, 1.6, 1.36, 3.5 and 3.2 MUM
      against A-549, PC-3, HCT 116, MCF-7 and MIA PaCa-2 cell lines, respectively.
      Mechanistic study of compound 16c revealed that it inhibits the colony formation
      and restrict the migration in HCT 116 cells in vitro. It also induces growth
      arrest with characterized morphological changes and loss of mitochondrial
      membrane potential (MMP) in a concentration dependent manner.

PMID- 28500965
TI  - Resting state functional connectivity in primary insomnia, generalized anxiety
      disorder and controls.
AB  - Sleep abnormalities are extremely common in anxiety disorders and may contribute
      to their development and persistence. Their shared pathophysiological mechanisms
      could thus serve as biomarkers or targets for novel therapeutics. Individuals
      with Primary Insomnia were age- and sex-matched to controls and to persons with
      Generalized Anxiety Disorder. All underwent fMRI resting-state scans at 3-T. In
      Primary Insomnia and controls, sleep was recorded for 2 weeks using diaries and
      actigraphy. All participants completed state-anxiety and neuroticism inventories.
      Whole-brain connectivity of 6 fear- and extinction-related seeds were compared
      between the 3 groups using ANOVA. The only significant between-group main effect
      was seen for connectivity between the left amygdala seed and a bilateral cluster
      in the rostral anterior cingulate cortex. The latter is believed to exert top
      down control over amygdala activity and their interaction may thus constitute an
      emotion regulatory circuit. This connectivity was significantly greatest in
      controls while Primary Insomnia was intermediate between that of controls and
      Generalized Anxiety Disorder. Across Primary Insomnia and control subjects, mean
      connectivity decreased with poorer sleep. Across all 3 groups, connectivity
      decreased with greater neuroticism and pre-scan anxiety. Decreased top-down
      control of the amygdala may increase risk of developing an anxiety disorder with
      preexisting Primary Insomnia.

PMID- 28500968
TI  - Stability and removal of selected avobenzone's chlorination products.
AB  - Stability studies of two avobenzone transformation products: chloro-avobenzone [2
      chloro-1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione] and dichloro
      avobenzone [2,2-dichloro-1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3
      propanedione] have been performed at different pHs values as well as under UV A
      light and compared with the stability of avobenzone, one of the mostly used UV A
      filter present in sunscreens. We have additionally investigated the possibility
      of application of TiO2 photocatalysis as a method for the removal of them.
      Results have shown the differences in pH stability of all three studied compounds
      with much slower degradation rate under neutral conditions in comparison to the
      acidic ones for all three studied compounds. In the case of photolytic
      experiment, performed under UV A light, dichloro-avobenzone exhibited the lowest
      UVA stability (half-life 22.4 +/- 0.7 min), while avobenzone and chloro
      avobenzone are much more stable and have shown quite similar degradation pattern
      (half-lives 126 +/- 16 min and 128 +/- 25 min). Under the photocatalytic
      conditions the less stable was dichloro-avobenzone (half-life 14.1 +/- 0.6 min),
      while chloro-avobenzone and avobenzone were much more stable (half-lives 41 +/- 3
      min and 79 +/- 13 min). Dichloroavobenzone is significantly more reactive than
      avobenzone and its monochloro-derivative. On the basis of the formation of
      various stable degradation products, including substituted acetophenones, benzoic
      acids and phenols, identified by GC-MS, the degradation pathway has been
      proposed.

PMID- 28500969
TI  - Oxidation of the antibacterial agent norfloxacin during sodium hypochlorite
      disinfection of marine culture water.
AB  - Chlorination disinfection and antibiotic addition are two universal processes of
      marine culture. The generation of disinfection byproducts (DBPs) is unavoidable.
      Antibiotic residue not only pollutes water but also acts as a precursor to the
      production of new DBPs. The fate of antibiotic norfloxacin (NOR) in chlorination
      disinfection was investigated. It was observed that NOR could be oxidized by
      disinfection agent sodium hypochlorite, but the oxidation rate varied
      considerably with the type of disinfected water. For fresh water, marine culture
      water and sea water, the reaction rate constant was 0.066 min-1, 0.466 min-1 and
      1.241 min-1, respectively. The difference was primarily attributed to the
      promotion role of bromide ions in seawater and marine culture water. Moreover,
      the bromide ions could result in the generation of brominated DBPs (Br-DBPs). The
      kinetics, products, reaction centers and mechanisms were investigated. The active
      site of NOR was found to be the N4 atom on piperazinyl in fresh water. During
      marine culture water and sea water disinfection, the carboxyl on NOR was oxidized
      and two Br-DBPs were formed. This was attributed to the lowering of the
      reaction's required activation energy when performed in the presence of bromide
      ions. The Br-DBPs were also confirmed in real shrimp pond brackish water.
      Quantitative structure activity relationships and the total organic halogen
      analysis showed that the DBPs in marine culture water possessed stronger
      toxicological properties than the DBPs in fresh water. The toxicity increase was
      attributed to the production of Br-DBPs in the disinfection process of marine
      culture water.

PMID- 28500970
TI  - Histopathological changes and lipid metabolism in the liver of Bufo gargarizans
      tadpoles exposed to Triclosan.
AB  - In the current study, the adverse effects of TCS on liver health of B.
      gargarizans tadpoles were assessed. B. gargarizans larvae were exposed to TCS at
      0, 10, 30, 60, and 150 MUg L-1 from Gosner stage 3 until metamorphic climax. The
      hepatosomatic index (HSI), hepatic histological and ultrastructural features, and
      transcript levels of genes associated with detoxification and oxidative stress as
      well as lipid metabolism in the livers were determined. Exposure to 150 MUg L-1
      TCS resulted in increased HSI of tadpoles at metamorphic climax. Histological
      changes characterized by an increase in the number of melanomacrophage, nucleus
      pyknosis, and deposition of collagen fibers were observed in liver at 60 and 150
      MUg L-1 TCS. Moreover, marked ultrastructural alterations including high electron
      dense in mitochondrial matrix and lipid accumulation were also observed. In
      addition, abundances of transcripts of Cu/Zn superoxide dismutase (SOD),
      phospholipid hydroperoxide glutathione peroxidase (PHGPx), and heat shock protein
      90 (HSP90) were decreased in larvae exposed to 60 and 150 MUg L-1 TCS, while
      transcript level of HSP90 was increased at 30 MUg L-1 TCS. Also, abundances of
      transcripts of acetyl-CoA carboxylase (ACC), carnitine palmitoyltransferase 2
      (CPT2), peroxisome proliferator-activated receptor alpha (PPARa), fatty acid
      elongase 1 (FAE), sterol carrier protein 2 (SCP) were significantly lesser in
      larvae exposed to 60 and 150 MUg L-1 TCS. Overall, TCS at high levels induced
      histopathological changes in the liver of B. gargarizans tadpoles. This might
      have been due to the alteration of oxidative stress-related genes and lipid
      metabolism-related genes expression levels.

PMID- 28500971
TI  - Assessment of the oxidative and neurotoxic effects of glyphosate pesticide on the
      larvae of Rhamdia quelen fish.
AB  - The aim of this work was to investigate the effects of glyphosate on the
      antioxidant system, as well as the neurotoxic effects on the larvae of Rhamdia
      quelen. A completely randomized design was implemented with the eggs of silver
      catfish distributed in 48 containers with 300 mL of water, which were subdivided
      randomly into two groups: control and treated with 6.5 mg L of glyphosate. These
      groups were evaluated at four time points (12 h, 24 h, 48 h, and 72 h), each with
      six replications. The survival rate of eggs/larvae (%) was evaluated, and samples
      were collected for antioxidant system analysis (catalase - CAT, glutathione
      transferase - GST, glutathione reductase - GR, and lipoperoxidation - LPO), and
      neurotoxic evaluation (cholinesterase - ChE). Throughout the 72 h of
      experimentation, there was a higher survival rate among the animals treated with
      glyphosate. The highest value of integrated biomarkers response (IBR = 1.26) was
      at 12 h, presenting induction of the cholinesterase (ChE) enzyme and GR. At 24 h,
      the value of IBR was -2.56, with inhibition of ChE and induction of GR. At 48 h,
      the value was -0.76, with induction of LPO. The lowest value of IBR was at 72 h (
      4.65), with induction of GST and inhibition of all other biomarkers. Finally, it
      was possible to detect an acute effect of glyphosate throughout the early
      development of R. quelen, with a decrease in the antioxidant system control and
      neurotoxic effects.

PMID- 28500972
TI  - Fate and transport of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and its
      degradation products in sedimentary and volcanic rocks, Los Alamos, New Mexico.
AB  - High-explosive compounds including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
      were used extensively in weapons research and testing at Los Alamos National
      Laboratory (LANL). Liquid effluents containing RDX were released to an outfall
      pond that flowed to Canon de Valle at LANL's Technical Area 16 (TA-16), resulting
      in the contamination of the alluvial, intermediate and regional groundwater
      bodies. Monitoring of groundwater within Canon de Valle has shown persistent RDX
      in the intermediate perched zone located between 225 and 311 m below ground
      surface. Monitoring data also show detectable levels of RDX putative anaerobic
      degradation products. Batch and column experiments were conducted to determine
      the extent of adsorption-desorption and transport of RDX and its degradation
      products (MNX, DNX, and TNX) in major rock types that are within the RDX plume.
      All experiments were performed in the dark using water obtained from a well
      located at the center of the plume, which is fairly oxic and has a neutral pH of
      7.5. Retardation factors and partitioning coefficient (Kd) values for RDX were
      calculated from batch experiments. Additionally, retardation factors and Kd
      values for RDX and its degradation products were calibrated from column
      experiments using a one-dimensional transport model with equilibrium sorption
      (linear isotherm). Results from the column and batch experiments showed little to
      no sorption of RDX to the aquifer materials tested, with retardation factors
      ranging from 1.0 to 1.8 and Kd values varying from 0 to 0.70 L/kg. Results also
      showed no measurable differences between the transport properties of RDX and its
      degradation products.

PMID- 28500973
TI  - Selenate redistribution during aging in different Chinese soils and the dominant
      influential factors.
AB  - To date, few works have attempted to determine the effect of soil types on
      Selenium aging process and the possible influential factors. In this study, the
      differences in Se speciation distribution and availability in 15 Chinese typical
      agricultural soils were investigated using spiked selenate for the entire year.
      Results evidenced that after one year of incubation, Se transformed from soluble
      fraction to Fe/Mn oxides and organic matter bound fractions in neutral or
      alkaline soils (pH 7.09-8.51) and from exchangeable fraction to residual fraction
      in acidic soils (pH 4.89-6.82). The available Se content in all soils declined
      rapidly at the initial stage of aging, with most of the neutral or alkaline soils
      reaching equilibrium after 109 d, whereas the acidic soils reached equilibrium
      after only 33-56 d. The available Se content in soil decreased constantly during
      the entire aging process in S4 (Xinjiang Gray desert soil), S12 (Anhui Yellow
      brown earths), and S15 (Hunan Krasnozems). Elovich model was the best model (R2 >
      0.80) in describing the Se aging process. Estimated time for exogenous Se
      reaching the distribution of available Se in corresponding native soils extended
      from 9.7 y to 50.2 y, indicating a much longer time was required for spiked soil
      to reach equilibrium. Soil pH was the most significant factor directly and
      negatively influencing the aging process (p < 0.05), while organic matter played
      a dual role on Se speciation. Results could provide reference for the selection
      of unified equilibrium time on Se-spiked experiment.

PMID- 28500974
TI  - Ongoing developments in RSV prophylaxis: a clinician's analysis.
AB  - Respiratory syncytial virus (RSV) is the most common respiratory pathogen in
      infants and young children worldwide. Lower respiratory tract infection due to
      RSV is one of the most common causes of hospitalization for infants, especially
      those born premature or with chronic lung or heart disease. Furthermore, RSV
      infection is an important cause of morbidity in adults, particularly in the
      elderly and immunocompromised individuals. The acute phase of this infection is
      often followed by episodes of wheezing that recur for months or years and usually
      lead to a physician diagnosis of asthma. RSV was discovered more than 50 years
      ago, and despite extensive research to identify pharmacological therapies, the
      most effective management of this infection remains supportive care. The trial of
      a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe
      illness upon natural infection. Currently, Palivizumab is the only available
      option for RSV prophylaxis, and because of restricted clinical benefits and high
      costs, it has been limited to a group of high-risk infants. There are several
      ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages
      for RSV vaccine development based on various strategies. Here we review the
      existing available prophylactic options, the current stages of RSV vaccine
      clinical trials, different strategies, and major hurdles in the development of an
      effective RSV vaccine.

PMID- 28500976
TI  - Personality disparity in chronic regional and widespread pain.
AB  - Chronic pain has high comorbidity with psychiatric disorders, therefore, better
      understanding of the relationship between chronic pain and mental illness is
      needed. This study aimed to investigate the pathway relationships among parental
      attachment, personality characteristics, alexithymic trait and mental health in
      patients with chronic widespread pain, those with chronic regional pain, and
      controls. Two hundred and thirty participants were recruited. The parental
      Bonding Inventory, Eysenck Personality Inventory (EPI), 20-item Toronto
      Alexithymia Scale (TAS-20), Chinese Health Questionnaire, and Short-Form 36 were
      filled out. The pathway relationships revealed that patients of mothers who were
      more protective were more neurotic, had more difficulty identifying feelings
      (DIF), worse mental health, and a higher association with chronic widespread
      pain. No differences were found between patients with chronic regional pain and
      the controls. The predisposing factors for chronic widespread pain, when compared
      with chronic regional pain, may be more closely related to psychiatric disorders.
      The pathways to chronic regional pain and chronic widespread pain differ, with
      neuroticism and the alexithymic DIF trait being the main factors defining chronic
      widespread pain. Therefore, besides therapies targeting pain symptoms,
      psychiatric consultation, medication and psychotherapy are also recommended for
      those with chronic widespread pain to alleviate their mental health conditions.

PMID- 28500977
TI  - Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes
      in human epithelial-like cells.
AB  - Liposomes are generally used as delivery systems, as they are capable of
      encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins,
      therapeutic drugs). However, liposomal drug delivery have to fulfill different
      requirements, such as the effective internalization by the target cells and
      avoidance of the degradative activity of the intracellular compartments. The use
      of polymer lipid complexes (PLCs), by including different polymers in the
      liposome formulation, could improve internalization and intracellular release of
      drugs. The aim of the present work is to study the mechanisms of cellular
      uptaking and the intracellular trafficking of PLCs formed with cholesterol-poly(2
      (dimethylamino)ethyl methacrylate) CHO-PDMAEMA and lecithin (LC CHO-PD). Calcein
      loaded liposomes were used to determine cellular uptake and intracellular
      localization by flow cytometry and confocal microscopy. Incorporation of CHO
      PDMAEMA to lecithin liposomes enhanced the internalization capacity of PLCs.
      Internalization of PLCs by human epithelial-like cells (HEK-293) diminished at 4
      degrees C, suggesting uptake by endocytosis. PLCs showed no co-localization with
      acidic compartments after internalization. Experiments with endocytosis
      inhibitors and co-localization of liposomes and albumin, suggested the caveolae
      endocytic pathway as the most probable route for intracellular trafficking of
      PLCs. In this work, we demonstrated an efficient uptake of LC CHO-PDs by human
      epithelial-like cells (HEK-293) through the non-degradative caveolae endocytic
      pathway. The mode of internalization and the intracellular fate of liposomes
      under study, suggest a promising use of LC CHO-PDs as drug delivery systems.

PMID- 28500975
TI  - Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential
      non-teratogenic valproate substitute to treat bipolar disorder.
AB  - BACKGROUND: Valproic acid (VPA), used for treating bipolar disorder (BD), is
      teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic
      VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain
      phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA
      synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic
      constitutional isomer of VPA amide, reported effective in BD, also inhibits
      recombinant Acsl-4 in vitro. HYPOTHESIS: VCD like VPA will reduce brain AA
      turnover in unanaesthetized rats. METHODS: A therapeutically relevant (50mg/kg
      i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA
      turnover and related parameters were determined using our kinetic model,
      following intravenous [1-14C]AA in unanaesthetized rats for 10min, and measuring
      labeled and unlabeled lipids in plasma and high-energy microwaved brain. RESULTS:
      VCD, compared with vehicle, increased lambda, the ratio of brain AA-CoA to
      unesterified plasma AA specific activities; and decreased turnover of AA in
      individual and total brain phospholipids. CONCLUSIONS: VCD's ability like VPA to
      reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in
      BD, suggest that VCD be further considered as a non-teratogenic VPA substitute
      for treating BD.

PMID- 28500978
TI  - Novel polyglycerol-dioleate based cubosomal dispersion with tailored physical
      characteristics for controlled delivery of ondansetron.
AB  - In this study different amphiphilic lipids viz. glycerylmonooleate (GMO),
      Glycerylmonolinoleate (GML), Plurol(r) (polyglycerol 3-dioleate), Soya
      phosphatidylcholine (Soya PC), Dipalmitoyl-phosphatidylcholine (DPPC) and
      Dipalmitoyl- phosphatidylglycerol (DPPG) were screened for their ability to form
      cubosomes and the formed particles were optimized for controlled delivery using
      ondansetron as a model drug. Polarized optical microscopy and high resolution
      transmission electron microscopy were performed to investigate the morphology of
      the prepared particles. A full factorial study was developed to optimize
      formulation composition and process conditions. Atomic force microscopy and in
      vitro drug release studies were done on selected formulae. Results showed that
      GMO, Plurol and GML were able to form cubosomes while DPPC was able to form
      spherical nanoparticles. There was a negative correlation between homogenization
      speed and PS, PDI and EE%. Furthermore, there was a significant positive
      correlation between Lipid: Polymer ratio and PS as well as PDI values, while
      there was a slight negative correlation between it and EE% in all nanoparticles
      except for those based on DPPC, which showed significant increase in EE% upon
      increase in the lipid:polymer ratio. Additionally, cumulative percent release of
      ondansetron from the particles shows that their design was efficiently tailored
      throughout this study to afford sustained drug release with diffusion pattern.
      T80 reached 19.3h in case of Plurol. Further confirmation studies on cubic
      structure formation were done on selected GMO and Plurol-based nanoparticles
      using scanning electron microscopy and x-ray powder diffraction. Results showed
      that Plurol was able to form cubic nanostrucures resembling those formed by GMO.
      Finally, Plurol (polyglyceroldioleate) showed to be a promising amphiphilic lipid
      that is capable of forming cubic nanostructures like GMO opening a new era for
      polyglycerols to take a step as a self assembling lipid resembling the
      unsaturated monoglycerols (UMGs).

PMID- 28500979
TI  - Ultra-sensitive and selective quantification of endothelin-1 in human plasma
      using ultra-performance liquid chromatography coupled to tandem mass
      spectrometry.
AB  - Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor peptide and the plasma
      concentrations are commonly quantified by immunoassays such as enzyme-linked
      immuno-sorbent assays (ELISA) with the disadvantage of possible cross-reactivity
      with closely related endothelin derivatives. The aim of this study was to develop
      and validate an ultra-sensitive and selective assay for the quantification of ET
      1 in human plasma, using ultra-performance liquid chromatography with tandem mass
      spectrometry (UPLC-MS/MS) after solid phase extraction. The assay fulfilled the
      requirements of the US Food and Drug Administration (FDA) and the European
      Medicines Agency (EMA) guidelines for assay validation, with a lower limit of
      quantification of 1.5pg/mL for ET-1. Recovery rates from plasma ranged between
      80.8% and 93.6%, and matrix effect varied between 121% and 135%. The assay was
      successfully applied to assess the time course of plasma ET-1 concentrations in
      two human volunteers after co-administration of bosentan and clarithromycin. In
      this trial, the concentrations measured by UPLC-MS/MS were slightly lower than
      those measured by ELISA, with a strong positive correlation between the two
      methods. Our novel UPLC-MS/MS method is applicable to the clinical setting and
      may have better selectivity for ET-1 than ELISA.

PMID- 28500980
TI  - Serum metabolomics reveals the mechanistic role of functional foods and exercise
      for obesity management in rats.
AB  - Obesity is one of the independent risk factors for several health problems,
      leading to metabolic perturbations and for which analytical approaches i.e.,
      "metabolomics" is needed to monitor the underlying metabolic changes. In this
      study, obesity associated changes were assessed via serum metabolites analysis of
      obese rats fed on high fat diet. Obese rats were subsequently treated with
      different functional foods used for obesity management including pomegranate,
      grapefruit, and red cabbage in parallel to swimming exercise. Serum samples were
      analyzed using gas chromatography-mass spectrometry (GC-MS) followed by
      multivariate data analysis to classify samples and determine if such treatments
      can help revert obesity related metabolic changes back to normal status. Results
      led to the identification of several novel metabolites biomarkers for obesity
      related to lipids, amino acids and central tricarboxylic acid (TCA) pathways.
      Distinct variations in metabolite levels were recorded in obese rats compared to
      normal ones including l-aspartic, l-alanine, l-glutamine, l-glycine,
      phenylethanolamine, alpha-aminobutyric acid and beta-hydroxybutyric acid.
      Metabolomics approach developed herein provides novel insight onto the metabolic
      disturbances associated with obesity, which will assist in future drug design
      that can help mitigate against such changes.

PMID- 28500981
TI  - Some consequences of normal aging for generating conceptual explanations: A case
      study of vitalist biology.
AB  - Accumulating evidence suggests that not only diseases of old age, but also normal
      aging, affect elderly adults' ability to draw on the framework theories that
      structure our abstract causal-explanatory knowledge, knowledge that we use to
      make sense of the world. One such framework theory, the cross-culturally
      universal vitalist biology, gives meaning to the abstract concepts life and
      death. Previous work shows that many elderly adults are animists, claiming that
      active, moving entities such as the sun and the wind are alive (Zaitchik &
      Solomon, 2008). Such responses are characteristic of young children, who, lacking
      an intuitive theory of biology, distinguish animals from non-animals on the basis
      of a theory of causal and intentional agency. What explains such childlike
      responses? Do the elderly undergo semantic degradation of their intuitive
      biological theory? Or do they merely have difficulty deploying their theory of
      biology in the face of interference from the developmentally prior agency theory?
      Here we develop an analytic strategy to answer this question. Using a battery of
      vitalist biology tasks, this study demonstrates-for the first time-that animism
      in the elderly is due to difficulty in deployment of the vitalist theory, not its
      degradation. We additionally establish some powerful downstream consequences of
      theory deployment difficulties, demonstrating that the elderly's use of the
      agency theory is not restricted to animist judgments-rather, it pervades their
      explicit reasoning about animates and inanimates. Extending the investigation, we
      identify specific cognitive mechanisms implicated in adult animism, finding that
      differences between young and elderly adults are mediated and moderated by
      differences in inhibition and shifting mechanisms. The analytic strategy
      developed here could help adjudicate between degradation and deployment in other
      conceptual domains and other populations.

PMID- 28500983
TI  - Night sleep influences white matter microstructure in bipolar depression.
AB  - BACKGROUND: Alteration of circadian rhythms and sleep disruption are prominent
      trait-like features of bipolar disorder (BD). Diffusion tensor imaging (DTI)
      measures suggest a widespread alteration of white matter (WM) microstructure in
      patients with BD. Sleep promotes myelination and oligodendrocyte precursor cells
      proliferation. We hypothesized a possible association between DTI measures of WM
      microstructure and sleep quantity measures in BD. METHODS: We studied 69
      inpatients affected by a depressive episode in course of type I BD. We used whole
      brain tract-based spatial statistics on DTI measures of WM microstructure: axial,
      radial, and mean diffusivity (AD, RD, MD), and fractional anisotropy (FA). Self
      assessed measures of time asleep (TA) and total sleep time (TST) were extracted
      from the Pittsburgh Sleep Quality Index (PSQI). Actigraphic recordings were
      performed on a subsample of 23 patients. RESULTS: We observed a positive
      correlation of DTI measures of FA with actigraphic measures of TA and TST, and
      with PSQI measure of TA. DTI measures of RD inversely associated with actigraphic
      measure of TA, and with PSQI measures of TA and TST. Several WM tracts were
      involved, including corpus callosum, cyngulate gyrus, uncinate fasciculus, left
      superior and inferior longitudinal and fronto-occipital fasciculi, thalamic
      radiation, corona radiata, retrolenticular part of internal capsule and
      corticospinal tract. LIMITATIONS: The study is correlational in nature, and no
      conclusion about a causal connection can be drawn. CONCLUSIONS: Reduced FA with
      increased RD and MD indicate higher water diffusivity associated with less
      organized myelin and/or axonal structures. Our findings suggest an association
      between sleep disruption and these measures of brain microstructure in specific
      tracts contributing to the functional connectivity in BD.

PMID- 28500984
TI  - The need for academic electronic health record systems in nurse education.
AB  - The nursing profession has been slow to incorporate information technology into
      formal nurse education and practice. The aim of this study was to identify the
      use of academic electronic health record systems in nurse education and to
      determine student and faculty perceptions of academic electronic health record
      systems in nurse education. A quantitative research design with supportive
      qualitative research was used to gather information on nursing students'
      perceptions and nursing faculty's perceptions of academic electronic health
      record systems in nurse education. Eighty-three participants (21 nursing faculty
      and 62 students), from 5 nursing schools, participated in the study. A purposive
      sample of 9 nursing faculty was recruited from one university in the Midwestern
      United States to provide qualitative data for the study. The researcher-designed
      surveys (completed by faculty and students) were used for quantitative data
      collection. Qualitative data was taken from interviews, which were transcribed
      verbatim for analysis. Students and faculty agreed that academic electronic
      health record systems could be useful for teaching students to think critically
      about nursing documentation. Quantitative and qualitative findings revealed that
      academic electronic health record systems regarding nursing documentation could
      help prepare students for the future of health information technology. Meaningful
      adoption of academic electronic health record systems will help in building the
      undergraduate nursing students' competence in nursing documentation with
      electronic health record systems.

PMID- 28500982
TI  - Abnormal sleep duration associated with hastened depressive recurrence in bipolar
      disorder.
AB  - BACKGROUND: Abnormal sleep duration (ASD, <6 or >=9h) is common in bipolar
      disorder (BD), and often persists beyond acute mood episodes. Few longitudinal
      studies have examined the ASD's impact upon BD illness course. The current study
      examined the longitudinal impact of ASD upon bipolar depressive
      recurrence/recovery. METHODS: Outpatients referred to the Stanford BD Clinic
      during 2000-2011 were assessed with the Systematic Treatment Enhancement Program
      for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the
      Clinical Monitoring Form at monthly follow-ups for up to two years of
      naturalistic treatment. Prevalence and clinical correlates of ASD in 93 recovered
      (euthymic >=8 weeks) and 153 depressed BD patients were assessed. Kaplan-Meier
      analyses (Log-Rank tests) assessed relationships between baseline ASD and
      longitudinal depressive severity, with Cox Proportional Hazard analyses assessing
      potential mediators. RESULTS: ASD was only half as common among recovered versus
      depressed BD outpatients, but was significantly associated with hastened
      depressive recurrence (Log-Rank p=0.007), mediated by lifetime anxiety disorder
      and attenuated by lifetime history of psychosis, and had only a non-significant
      tendency towards association with delayed depressive recovery (Log-Rank p=0.07).
      In both recovered and depressed BD outpatients, baseline ASD did not have
      significant association with any baseline BD illness characteristic. LIMITATIONS:
      Self-reported sleep duration. Limited generalizability beyond our predominately
      white, female, educated, insured American BD specialty clinic sample.
      CONCLUSIONS: Baseline ASD among recovered BD patients may be a risk marker for
      hastened depressive recurrence, suggesting it could be an important therapeutic
      target between mood episodes.

PMID- 28500985
TI  - Low dose computed tomography pulmonary angiography protocol for imaging pregnant
      patients: Can dose reduction be achieved without reducing image quality?
AB  - OBJECTIVE: To assess the effect of low dose computed tomography pulmonary
      angiography (CTPA) on radiation dose in pregnant patients. MATERIALS AND METHODS:
      An old CTPA protocol for pregnant patients was compared to a new protocol.
      Protocol changes included: decreased kVp; increased contrast injection rate;
      imaging after shallow inspiration. Patients undergoing CTPA before (phase 1
      group) or after (phase 2 group) the protocol change, were assessed. RESULTS:
      Effective dose was lower in the phase 2 group (0.95 v 1.66 mSv; p<0.001).
      Quantitative noise was lower in the phase 1 group (p<0.001). CONCLUSION: Low dose
      CTPA tailored for pregnancy reduces dose in pregnant patients.

PMID- 28500986
TI  - Intradermal invasive lobular carcinoma presenting: Not everything in the skin is
      benign.
AB  - In this case report, the history and imaging of two patients with invasive
      lobular carcinoma (ILC) in the skin are presented, followed by a discussion of
      both benign and malignant intradermal findings on breast ultrasound. Although the
      majority of dermal findings are benign, these cases are a reminder that
      malignancy can manifest within the skin. The purpose of presenting these cases
      together is to remind breast imagers of the importance of considering malignancy
      in the differential diagnosis of intradermal lesions on breast ultrasound,
      especially in special circumstances such as a personal history of breast cancer
      or associated clinical findings.

PMID- 28500987
TI  - Optimization of NBED simulations for disc-detection measurements.
AB  - Nano-beam electron diffraction (NBED) is a method which can be applied to measure
      lattice strain and polarisation fields in strained layer heterostructures and
      transistors. To investigate precision, accuracy and spatial resolution of such
      measurements in dependence of properties of the specimen as well as electron
      optical parameters, simulations of NBED patterns are required which allow to
      predict the result of common disc-detection algorithms. In this paper we
      demonstrate by focusing on the detection of the central disc in crystalline
      silicon that such simulations require to take several experimental
      characteristics into account in order to obtain results which are comparable to
      those from experimental NBED patterns. These experimental characteristics are the
      background intensity, the presence of Poisson noise caused by electron statistics
      and blurring caused by inelastic scattering and by the transfer quality of the
      microscope camera. By means of these optimized simulations, different effects of
      specimen properties on disc detection - such as strain, surface morphology and
      compositional changes on the nanometer scale - are investigated and discussed in
      the context of misinterpretation in experimental NBED evaluations. It is shown
      that changes in surface morphology and chemical composition lead to measured
      shifts of the central disc in the NBED pattern of tens to hundreds of urad. These
      shifts are of the same order of magnitude or even larger than shifts that could
      be caused by an electric polarisation field in the range of MV/cm.

PMID- 28500988
TI  - Comparison of Faradaic reactions in capacitive deionization (CDI) and membrane
      capacitive deionization (MCDI) water treatment processes.
AB  - Capacitive deionization (CDI) and membrane capacitive deionization (MCDI) are the
      most common cell architectures in the use of CDI for water treatment. In this
      work, the Faradaic reactions occurring in batch-mode CDI and MCDI processes were
      compared by investigating the variation of H2O2 and dissolved oxygen (DO)
      concentrations, pH, conductivity and current during charging and discharging
      under different charging voltages. During charging, the H2O2 concentration in CDI
      increased rapidly and then decreased while almost no H2O2 was generated in MCDI
      due to the inability of oxygen to penetrate the ion exchange membrane. Chemical
      kinetic models were developed to quantitatively describe the variation of H2O2
      concentration and found to present satisfactory descriptions of the experimental
      data. The pH drop during charging could be partially explained by Faradaic
      reactions with proton generation associated with oxidation of the carbon
      electrodes considered to be the major contributor. The electrode potentials
      required for the induction of Faradaic reactions were analyzed with this analysis
      providing robust thermodynamic explanations for the occurrence of carbon
      oxidation at the anode and H2O2 generation at the cathode during the ion
      adsorption process. Finally, electrochemically-induced ageing of the carbon
      electrodes and the resulting performance stability were investigated. The
      findings in this study contribute to a better understanding of Faradaic reactions
      in CDI and MCDI and should be of value in optimizing CDI-based technologies for
      particular practical applications.

PMID- 28500989
TI  - Pharmaceuticals, benzene, toluene and chlorobenzene removal from contaminated
      groundwater by combined UV/H2O2 photo-oxidation and aeration.
AB  - This study was performed to test the feasibility of several decontamination
      methods for remediating heavily contaminated groundwater in a real contaminated
      locality in the Czech Republic, where a pharmaceuticals plant has been in
      operation for more than 80 years. The site is polluted mainly by recalcitrant
      psychopharmaceuticals and monoaromatic hydrocarbons, such as benzene, toluene and
      chlorobenzene. For this purpose, an advanced oxidation technique employing UV
      radiation with hydrogen peroxide dosing was employed, in combination with simple
      aeration pretreatment. The results showed that UV/H2O2 was an efficient and
      necessary step for degradation of the pharmaceuticals; however, the monoaromatics
      were already removed during the aeration step. Characterization of the removal
      mechanisms participating in the aeration revealed that volatilization, co
      precipitation and biodegradation contributed to the process. These findings were
      supported by bacterial metabolite analyses, phospholipid fatty acid analysis,
      qPCR of representatives of the degradative genes and detailed characterization of
      the formed precipitate using Mossbauer spectroscopy and scanning electron
      microscopy. Further tests were carried out in a continuous arrangement directly
      connected to the wells already present in the locality. The results documented
      the feasibility of combination of the photo-reactor employing UV/H2O2 together
      with aeration pretreatment for 4 months, where the overall decontamination
      efficiency ranged from 72% to 99% of the pharmaceuticals. We recorded even better
      results for the monoaromatics decontamination except for one month, when we
      encountered some technical problems with the aeration pump. This demonstrated the
      necessity of using the aeration step.

PMID- 28500990
TI  - Evaluating the safety impact of adaptive cruise control in traffic oscillations
      on freeways.
AB  - Adaptive cruise control (ACC) has been considered one of the critical components
      of automated driving. ACC adjusts vehicle speeds automatically by measuring the
      status of the ego-vehicle and leading vehicle. Current commercial ACCs are
      designed to be comfortable and convenient driving systems. Little attention is
      paid to the safety impacts of ACC, especially in traffic oscillations when crash
      risks are the highest. The primary objective of this study was to evaluate the
      impacts of ACC parameter settings on rear-end collisions on freeways. First, the
      occurrence of a rear-end collision in a stop-and-go wave was analyzed. A car
      following model in an integrated ACC was developed for a simulation analysis. The
      time-to-collision based factors were calculated as surrogate safety measures of
      the collision risk. We also evaluated different market penetration rates
      considering that the application of ACC will be a gradual process. The results
      showed that the safety impacts of ACC were largely affected by the parameters.
      Smaller time delays and larger time gaps improved safety performance, but
      inappropriate parameter settings increased the collision risks and caused traffic
      disturbances. A higher reduction of the collision risk was achieved as the ACC
      vehicle penetration rate increased, especially in the initial stage with
      penetration rates of less than 30%. This study also showed that in the initial
      stage, the combination of ACC and a variable speed limit achieved better safety
      improvements on congested freeways than each single technique.

PMID- 28500991
TI  - Thermoluminescence characteristics of a chondrite (Holbrook) and an aubrite
      achondrite (Norton County) meteorites.
AB  - The present study constitutes the first part of a meteorite project, currently in
      progress, towards the full and thorough dosimetric study (TL and OSL) of two
      different meteorites of recent fall, Norton County and Holbrook. Both meteorites
      exhibit strong TL sensitivity, linear dose response and no saturation for doses
      up to 2kGy. However, the two meteorites exhibited a very dissimilar TL glow curve
      and behaviour regarding sensitization and fading. Notably, the Norton County
      aubrite achondrite was found to exhibit a strong fading of the high-temperature
      peak (~300 degrees C), attributed to anomalous fading, whereas Holbrook did not
      seem to show signs of anomalous fading. Since quantitative conclusions regarding
      the thermal and irradiation history of meteorites, require knowledge of the
      detailed peak structure of the glow curve and deeper understanding of the
      trapping mechanism, the glow curves, after irradiation in the range 10-2000Gy,
      were deconvoluted using general order kinetics. The fitting parameters extracted
      point towards complex non-strictly first order mechanisms with a multitude of
      traps acting very differently. All the above, combined with future OSL
      measurements, currently in progress, are expected to shed light on the nature of
      the involved traps in both phenomena (energy depth, light-resistance etc), which
      would allow to extract more concrete conclusions about their history.

PMID- 28500993
TI  - Nonsynonymous changes of equine lentivirus receptor-1 (ELR1) gene in amino acids
      involved in the interaction with equine infectious anemia virus (EIAV).
AB  - Equine lentivirus receptor-1 (ELR1) has been characterized as the specific
      functional receptor that mediates equine infectious anemia virus (EIAV) entrance
      to horse macrophages. This receptor is tumor necrosis factor receptor superfamily
      member 14 (TNFRSF14). The aim of this study was to investigate the occurrence of
      allelic variants in the coding sequence of equine TNFRSF14 gene by screening for
      single-nucleotide polymorphisms (SNPs) in different equine populations. Forty
      seven horse samples were randomly selected from a reservoir of EIAV-seropositive
      and seronegative samples collected from different outbreaks and regions of
      Argentina. DNA samples were scanned via PCR and direct sequencing of exon 3 and
      exon 5 of TNFRSF14 gene. A total of 21 SNPs were identified, of which 11 were
      located in coding sequences. Within exon 5, four SNPs caused nonsynonymous
      substitutions, while two other SNPs caused synonymous substitutions in crucial
      residues (Ser112 and Thr114) implicated in the interaction with EIAV. Despite
      some of exon 5 variants occurred exclusively in EIAV-positive or EIAV-negative
      horses, critical residues for the function of the mature protein were conserved,
      accounting for selective pressures in favor of preserving the specific function
      of TNFRSF members and the host immune response. To our knowledge, this is the
      first report of the existence of allelic variations involving some crucial amino
      acid residues in horse ELR1. Further, it could be an initial step to test the
      possible functional relevance and relationship of these variants with EIAV
      infection and disease progression as well as to develop preventive strategies.

PMID- 28500992
TI  - Multi-transmitter neurons in the mammalian central nervous system.
AB  - It is firmly established that many mammalian neurons release various combinations
      of amino acids, their derivatives, and other small molecules from presynaptic
      terminals in order to signal to their postsynaptic targets. Here we discuss
      recent findings about four types of multi-transmitter neurons-those that release
      GABA and acetylcholine (Ach); dopamine (DA) and GABA or glutamate; and glutamate
      and GABA. The mechanisms of co-release in each class differ and highlight the
      complex and dynamic nature of neurotransmitter release. Furthermore, identifying
      the neurotransmitter signature of each neuron and the post-synaptic targets of
      each neurotransmitter remain challenging. The existence of multi-transmitter
      neurons complicates the interpretation of connectomic wiring diagrams and poses
      interesting challenges for our understanding of circuit function in the brain.

PMID- 28500994
TI  - Salt-tolerance mechanisms induced in Stevia rebaudiana Bertoni: Effects on
      mineral nutrition, antioxidative metabolism and steviol glycoside content.
AB  - In order to cope with challenges linked to climate change such as salinity,
      plants must develop a wide spectrum of physiological and molecular mechanisms to
      rapidly adapt. Stevia rebaudiana Bertoni plants are a case in point. According to
      our findings, salt stress has no significant effect on plant growth in these
      plants, which accumulate sodium (Na+) in their roots, thus avoiding excessive Na+
      accumulation in leaves. Furthermore, salt stress (NaCl stress) increases the
      potassium (K+), calcium (Ca2+), chloride ion (Cl-) and proline concentrations in
      Stevia leaves, which could contribute to osmotic adjustment. We also found that
      long-term NaCl stress does not produce changes in chlorophyll concentrations in
      Stevia leaves, reflecting a mechanism to protect the photosynthesis process.
      Interestingly, an increase in chlorophyll b (Chlb) content occured in the oldest
      plants studied. In addition, we found that NaCl induced reactive oxygen species
      (ROS) accumulation in Stevia leaves and that this accumulation was more evident
      in the presence of 5 g/L NaCl, the highest concentration used in the study.
      Nevertheless, Stevia plants are able to induce (16 d) or maintain (25 d)
      antioxidant enzymes to cope with NaCl-induced oxidative stress. Low salt levels
      did not affect steviolbioside and rebaudioside A contents. Our results suggest
      that Stevia plants induce tolerance mechanisms in order to minimize the
      deleterious effects of salt stress. We can thus conclude that saline waters can
      be used to grow Stevia plants and for Steviol glycosides (SGs) production.

PMID- 28500995
TI  - Antibacterial activity and mechanism of action of the benzazole acrylonitrile
      based compounds: In vitro, spectroscopic, and docking studies.
AB  - A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an
      efficient procedure. The antibacterial activity of the new compounds was studied
      against four bacterial strains. Compound 5 was found to exhibit the highest
      potency, with = 1.0 MUg/ml, against both Escherichia coli and Pseudomonas
      aeruginosa when compared with amoxicillin (MIC = 1.0-1.5 MUg/mL). Transmission
      electron microscope results confirmed that activities against bacteria occurred
      via rupturing of the cell wall. Molecular modeling results suggested that
      compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the
      penicillin-binding protein (PBP) Ser62 residue in the active site and were able
      to overcome amoxicillin resistance in bacteria by inhibiting the beta-lactamase
      enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the beta
      lactamase enzyme through covalent bonding with Ser70. The synergistic effect with
      amoxicillin was studied. The newly synthesized compounds reported in this study
      warrant further consideration as prospective antimicrobial agents.

PMID- 28500996
TI  - Professor Kerstin Hall (1929-1917): Pioneer in the field of growth hormone and
      IGF research.

PMID- 28500997
TI  - Does a policy of earlier induction affect labour outcomes in women induced for
      postmaturity? A retrospective analysis in a tertiary hospital in the North of
      England.
AB  - OBJECTIVES: to investigate whether a change in the management of postmature
      pregnancy to earlier induction affects the length of labour and the induction
      process. Secondly, to assess the feasibility of the research process to inform a
      future larger study. DESIGN: a change in management of postmature pregnancy in an
      NHS hospital in October 2013, from induction at 42 weeks gestation to induction
      between 41-42 weeks, provided an opportunity to conduct a retrospective analysis.
      Pre-existing data from the maternity database and casenotes were collected and
      primary outcomes analysed using the Mann-Whitney test and the Hodges-Lehman
      confidence interval for differences in medians. SETTING: a large city based
      tertiary referral hospital in the North of England. PARTICIPANTS: 125 women
      induced before the change in policy were compared with 309 women induced after
      the change. MEASUREMENTS: primary outcomes were length of 1st and 2nd stage of
      labour, overall length of labour, length of induction to established labour and
      length of induction to birth. FINDINGS: the median overall length of labour for
      women induced at 42 weeks was 6.5hours, while for women induced at 41-42 weeks
      this was 5.2hours. The difference was not statistically significant (p=0.15, 95%
      CI for median difference -0.27 to 1.93hours) with a small effect size (Pearson's
      r=-0.08). The median length of induction to birth was 13.6hours for women induced
      at 42 weeks and 16.5hours for women induced at 41-42 weeks. This difference was
      also not statistically significant (p=0.14, 95% CI for median difference -7.25 to
      1.20hours) with a small effect size (Pearson's r=-0.13). KEY CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: This study demonstrated no statistically significant
      differences in length of labour and induction following a change in the
      management of postmature pregnancy to earlier induction. A large study is needed
      to establish definitively the effects of earlier induction on labour outcomes.

PMID- 28500998
TI  - The impact of surface and geometry on coefficient of friction of artificial hip
      joints.
AB  - Coefficient of friction (COF) tests were conducted on 28-mm and 36-mm-diameter
      hip joint prostheses for four different material combinations, with or without
      the presence of Ultra High Molecular Weight Polyethylene (UHMWPE) particles using
      a novel pendulum hip simulator. The effects of three micro dimpled arrays on
      femoral head against a polyethylene and a metallic cup were also investigated.
      Clearance played a vital role in the COF of ceramic on polyethylene and ceramic
      on ceramic artificial hip joints. Micro dimpled metallic femoral heads yielded
      higher COF against a polyethylene cup; however, with metal on metal prostheses
      the dimpled arrays significantly reduced the COF. In situ images revealed
      evidence that the dimple arrays enhanced film formation, which was the main
      mechanism that contributed to reduced friction.

PMID- 28500999
TI  - Effects of working gas pressure on zirconium dioxide thin film prepared by pulsed
      plasma deposition: roughness, wettability, friction and wear characteristics.
AB  - In joint arthroplasty one of the main issues related to the failure of prosthetic
      implants is due to the wear of the ultra-high molecular weight polyethylene
      (UHMWPE) component. Surface treatments and coatings have been recognized as
      enhancing methods, able to improve the tribological properties of the implants.
      Therefore, the main objective of this work was to investigate the possibility to
      fabricate yttria-stabilized zirconia (YSZ) coatings on a metal (AISI 316-L)
      substrate by means of Pulsed Electron Deposition, in order to improve the
      tribological behavior of the polymer-metal coupling, by reducing the initial wear
      of the UHMWPE component. In order to optimize the coating characteristics, the
      effects of working gas pressure on both its morphological and tribological
      properties were analyzed. Morphological characterization of the films was
      evaluated by Atomic Force Microscopy (AFM). Coating wettability was also
      estimated by contact angle (CA) measurement. Tribological performance (coupling
      friction and wear of UHMWPE) was evaluated by using a ball-on-disc tribometer
      during highly-stressing tests in dry and lubricated (i.e. NaCl and serum)
      conditions; friction and wear were specifically evaluated at the initial sliding
      distances - to highlight the main effect of coating morphology - and after 100m -
      where the influence of the intrinsic materials properties prevails. AFM analysis
      highlighted that the working pressure heavily affected the morphological
      characteristics of the realized films. The wettability of the coating at the
      highest and lowest deposition pressures (CA ~ 60 degrees , closed to substrate
      value) decreased for intermediate pressures, reaching a maximum CA of ~ 90
      degrees . Regarding tribological tests, a strong correlation was found in the
      initial steps between friction coefficient and wettability, which decreased as
      the distance increased. Concerning UHMWPE wear associated to coated counterpart,
      at 100m a reduction rate of about 7% in dry, 12% in NaCl and 5% in presence of
      serum was obtained compared to the uncoated counterpart. Differently from what
      highlighted for friction, no correlation was found between wear rate and
      morphological parameters. These findings, in agreement with literature,
      underlined the effect of the deposition pressure on the morphological properties,
      but suggested that physical characteristics are influenced too. Further research
      on the deposition process will be required in order to improve the tribological
      performance of the coating at long distances, addressing - above all - orthopedic
      applications.

PMID- 28501000
TI  - Combination of a biodegradable three-dimensional (3D) - printed cage for
      mechanical support and nanofibrous membranes for sustainable release of
      antimicrobial agents for treating the femoral metaphyseal comminuted fracture.
AB  - The aim of this study was to develop a biodegradable three-dimensional-printed
      polylactide (PLA) cage for promoting bony fixation and an antibiotics-embedded
      poly(d,l)-lactide-co-glycolide (PLGA) nanofibrous membrane for infectious
      prophylaxis during treating the comminuted metaphyseal fracture in a rabbit
      femoral model. The in vitro studies included measuring the mechanical properties
      of the 3D printed cage and determining release activities of vancomycin and
      ceftazidime from the nanofibers. The in vivo study included comparisons of
      rabbits of the femoral metaphyseal comminuted fracture treated with or without
      the combined biodegradable polymers. The results showed that vancomycin and
      ceftazidime were sustainably detected above the effective levels in the local
      tissue fluid around the fracture site for 3 weeks. The animal studies showed that
      rabbits with the 3D cage implantation possessed better cortical integrity, leg
      length ratio, and maximal bending strengths. The study results indicate that
      these combined polymers may promote fracture fixation during treating the rabbit
      femoral metaphyseal comminuted fracture.

PMID- 28501001
TI  - One-pot chemo-enzymatic synthesis of furfuralcohol from xylose.
AB  - Furfuralcohol (FOL) is an important intermediate for the production of lysine,
      ascorbic acid, and lubricants. It can be used as a hypergolic fuel in rocketry.
      In this study, it was attempted to synthesize FOL from xylose by tandem catalysis
      with solid acid SO42-/SnO2-Montmorillonite and recombination Escherichia coli
      CCZU-K14 whole cells. Using SO42-/SnO2-Montmorillonite (3.0wt% dosage) as
      catalyst, a highest furfural yield of 41.9% was achieved from xylose at 170
      degrees C for 20min. Furthermore, Escherichia coli CCZU-K14 whole cells were used
      for bioconverting furfural to FOL. The optimum biocatalytic reaction temperature,
      reaction pH, cosubstrate concentration, and substrate concentration were 30
      degrees C, 6.5, 1.5mol glucose/mol furfural, and 200mM, respectively. Finally,
      the yield of FOL from 200mM furfural was achieved to 100% by Escherichia coli
      CCZU-K14 whole cells after 24h. In conclusion, this strategy show high potential
      application for the effective synthesis of FOL.

PMID- 28501002
TI  - Effects of lactic acid bacteria and molasses additives on the microbial community
      and fermentation quality of soybean silage.
AB  - The objective was to study effects of lactic acid bacteria (L) and molasses (M)
      on the microbial community and fermentation quality of soybean silage. Soybean
      was ensiled with no additive control (C), 0.5% molasses (0.5%M), 0.5%M+L
      (0.5%ML), 2%M, 2%M+L (2%ML) for 7, 14, 30 and 60days. The M-treated silages could
      increase the content of lactic acid and decrease butyric acid than control.
      Besides, higher crude protein was also observed in M-treated silages. With
      prolonged ensiling time, there was a reduction of the ratio of lactic acid/acetic
      acid in the 2%M-treated and 2%ML-treated silages. The combined addition of L and
      2%M could enhance the account of desirable Lactobacillus and inhibit the growth
      of undesirable microorganism such as Clostridia and Enterobacter. In summary, the
      silage quality of soybean was improved with the addition of L and M.

PMID- 28501003
TI  - Phytochemicals for taming agitated immune-endocrine-neural axis.
AB  - Homeostasis of immune-endocrine-neural axis is paramount for human health. If
      this axis gets agitated due to age, genetic variations, environmental exposures
      or lifestyle assaults, a cascade of adverse reactions occurs in human body.
      Cytokines, hormones and neurotransmitters, the effector molecules of this axis
      behave erratically, leading to a gamut of neural, endocrine, autoimmune, and
      metabolic diseases. Current panel of drugs can tackle some of them but not in a
      sustainable, benign way as a myriad of side effects, causal of them have been
      documented. In this context, phytochemicals, the secondary metabolites of plants
      seem beneficial. These bioactive constituents encompassing polyphenols,
      alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol),
      saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert
      antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic,
      anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective,
      neuroprotective, dermatoprotective, and antimicrobial properties, among a litany
      of other biological effects. This review presents a holistic perspective of
      common afflictions resultant of immune-endocrine-neural axis disruption, and the
      phytochemicals capable of restoring their normalcy and mitigating the ailments.

PMID- 28501004
TI  - Adipose-derived mesenchymal stem cells slow disease progression of acute-on
      chronic liver failure.
AB  - A serious complication of chronic hepatic insufficiency is acute-on-chronic liver
      failure, a recognized syndrome characterized by acute decompensation of cirrhosis
      and organ/system failure. We investigated the use of adipose-derived mesenchymal
      stem cells (AD-MSCs) in an experimental model of acute-on-chronic liver failure,
      developed by microsurgical extrahepatic cholestasis in rats. Rats undergoing
      microsurgical extrahepatic cholestasis were treated by intraparenchymal liver
      injection of human or rat AD-MSCs, undifferentiated or previously differentiated
      in vitro toward the hepatocyte lineage. The groups treated with rat AD-MSCs
      showed less ascites, lower hepato- and splenomegaly, less testicular atrophy, and
      an improvement in serum biochemical hepatic parameters. There was also an
      improvement in histological liver changes, in which the area of fibrosis and bile
      duct proliferation were significantly decreased in the group treated with
      predifferentiated rat AD-MSCs. In conclusion, an isograft of hepatocyte
      predifferentiated AD-MSCs injected intraparenchymally 2 weeks after microsurgery
      in extrahepatic cholestatic rats prevents secondary complications of acute-on
      chronic hepatic failure. These data support the potential use of autologous AD
      MSCs in the treatment of human cholestasis, and specifically of newborn biliary
      atresia, which could be beneficial for patients awaiting transplant.

PMID- 28501005
TI  - HuR promotes breast cancer cell proliferation and survival via binding to CDK3
      mRNA.
AB  - HuR, a ubiquitously expressed RNA-binding protein, stabilizes mRNA and regulates
      its translation. HuR expression was increased at all stages of breast cancer and
      correlated with poor clinical outcome. However, the detailed mechanisms remain
      unclear. Here we reported that overexpression of HuR increased CDK3 mRNA
      stability and thus its protein expression in MDA-MB-231 and MCF-7 cells.
      Mechanistically, CDK3 mRNA was identified as a target of HuR via bioinformatics
      and RNA binding protein immunoprecipitation (RIP) assays. Furthermore, treatment
      with HuR shRNA decreased CDK3 expression, inhibited cell proliferation and
      promoted cell apoptosis in breast cancer. More importantly, overexpression of
      CDK3 reversed the suppressive effects of HuR knockdown on cell growth in both MDA
      MB-231 and MCF-7 cells. Finally, HuR and CDK3 expression levels were positively
      correlated and significantly up-regulated in breast cancer samples. And
      overexpression of HuR attenuated the chemotherapeutical efficiency of breast
      cancer. Therefore, our results indicate that ectopic expression of HuR promotes
      breast cancer cell proliferation and survival by directly binding to and
      stabilizing CDK3 mRNA.

PMID- 28501006
TI  - Liquid chromatography-mass spectrometry-based quantitative proteomics analysis
      reveals chondroprotective effects of astragaloside IV in interleukin-1beta
      induced SW1353 chondrocyte-like cells.
AB  - OBJECTIVE: Chondrocyte apoptosis played a key role on the progression of
      Osteoarthritis (OA). Safe and effective drugs are urgently needed for the
      treatment of OA. Previous study reported that Astragaloside IV (ASG-IV) had
      exerted a protective effect against articular cartilage degeneration by promoting
      rapid proliferation of chondrocyte. Therefore, the aim of our study is to explore
      the effects and mechanisms of ASG-IV in chondrocyte apoptosis. METHODS: Isobaric
      Tags For Relative And Absolute Quantitation (iTRAQ)-based quantitative proteomics
      was used to quantitatively detect and map proteins in SW1353 chondrocyte-like
      cells pre-treated with ASG-IV or interleukin-1beta (IL-1beta) or ASG-IV+IL-1beta.
      The iTRAQ-labeled peptides were fractionated by high-accuracy liquid
      chromatography-mass spectrometry (LC-MS). Cell apoptosis and differentially
      expressed proteins was detected by flow cytometry (FCM), quantitative real-time
      polymerase chain reaction (qRT-PCR), and western blotting, respectively. RESULTS:
      The apoptosis of the IL-1beta-induced SW1353 cells treated with ASG-IV was
      greatly inhibited. Bioinformatics analysis revealed that gamma actin 1 (ACTG1)
      and Yes Associated Protein 1 (YAP1), participating in the Hippo signaling pathway
      and Vitronectin (VTN) and Collagen Type I Alpha 1 Chain (COL1A1), involving in
      the extracellular matrix (ECM)-receptor interaction signaling pathway, were all
      significantly up-regulated in the IL-1beta-induced SW1353 cells after treatment
      with ASG-IV. The qRT-PCR and Western blotting results confirmed the up-regulation
      of these four genes. CONCLUSION: ASG-IV played a positive role in human
      osteoarthritic chondrocyte apoptosis, possibly through modulation of the Hippo
      signaling pathway by up-regulating YAP1and ACTG1 expression, and also by up
      regulating VTN and COL1A1, which are involved in the ECM-receptor interaction
      pathway. Taken together, all the results suggested that ASG-IV had a novel
      therapeutic potential for the treatment of OA.

PMID- 28501007
TI  - MiR-330 inhibits IL-22-induced keratinocyte proliferation through targeting
      CTNNB1.
AB  - Psoriasis is a common chronic inflammatory skin disease which is characterized by
      hyperproliferation and aberrant differentiation of keratinocytes; however the
      exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated
      its vital role in T cell-mediated immune response by interacting with
      keratinocytes in the pathogenesis of psoriasis. The microRNAs (miRNAs) are a
      class of small non-coding RNA molecules that play important roles in cellular
      processes by regulating gene expression at the post-transcriptional level. MiR
      330 has been reported to inhibit the proliferation and migration of mouse
      keratinocytes. In the present study, we indicated that miR-330 expression in
      lesion tissue of psoriasis patients was specifically down-regulated, and could
      inhibit IL-22-induced proliferation of HaCaT and HKC cell. Wnt/beta-catenin
      pathway plays an essential role in the pathogenesis of psoriasis. By direct
      targeting CTNNB1, miR-330 could significantly downregulate IL-22-induced CTNNB1
      expression. In addition, we found that the downstream targets of beta-catenin,
      CyclinD1 and Axin2, could be affected by miR-330; miR-330 could suppress CyclinD1
      protein expression and rescue Axin2 protein expression. Taken together, we
      indicated miR-330 inhibits IL-22-induced proliferation of HaCaT and HKC cell by
      targeting CTNNB1 and subsequently affect the downstream factors, CyclinD1 and
      Axin2 for the first time, and provide diagnostic markers and a novel target for
      psoriasis treatment.

PMID- 28501009
TI  - miR-205 as a biological marker in non-small cell lung cancer.
AB  - OBJECTION: The aim of this study is to explain the significance and mechanism of
      miR-205 in the diagnosis and treatment of non-small cell lung cancer. METHODS:
      The 70 advanced NSCLC patients, treated in our hospital, were collected from
      2011.10 to 2013.9, taking the tissues from cancer and adjacent tissues to measure
      the miR-205 expression, evaluate the AKT gene and protein expression of cancer
      and adjacent normal tissues by RT-PCR and Immunohistochemistry (IHC) assays and
      analyzing the correlation between miR-205 and AKT. Following up the patients for
      2 years; Recording patients' survival time. In the cell experiment, Selecting
      A549 cell as research object, the cells were divided into three groups: Normal
      control group (NC), Blank control group (BL) and si-miR-205 transfection group
      (si-miR-205). Cell proliferation rate and apoptosis rate were detected by MTT
      method and flow cytometry; Measuring invasion and migration of difference groups
      by transwell and scratch testing, measured the Akt, mTOR,P21, MMP2 and MMP9 gene
      expression and detected Akt, p-Akt, mTOR, p-mTOR, P21, MMP2 and MMP 9 protein
      expression levels. RESULTS: Compared with adjacent normal tissue, the miR-205 and
      AKT gene expression level was significantly increased in NSCLC tissues (P<0.05)
      and the AKT protein expression was stronger than that of healthy tissues, miR-205
      was positive correlation with AKT; In the overall survival, MiR-205 high
      expression group was significantly higher than low expression group (P<0.05). In
      the cell experiment, Compared with NC and BL groups, si-miR-205 could
      significantly reduced the biological activity of A549 cells in proliferation,
      invasion and migration, and promoted the apoptosis of A549 cells (P<0.05,
      respectively). Akt, p-Akt, mTOR, p-mTOR, P21, MMP 2 and MMP 9 gene and protein
      expression of si-miR-205 group were significantly compared with NC and BL groups
      (P<0.05, respectively). CONCLUSION: miRNA-205 might serve as a potential
      biomarker for the prognosis of advanced NSCLC, and inhibiting miR-205 expression
      could decrease A549 cells biological activity by regulating Akt/mTOR/P21 and
      Akt/MMP 2/MMP 9signaling pathway.

PMID- 28501008
TI  - Ethanol extract and its dichloromethane fraction of Alpinia oxyphylla Miquel
      exhibited hepatoprotective effects against CCl4-induced oxidative damage in vitro
      and in vivo with the involvement of Nrf2.
AB  - Alpinia oxyphylla Miq. (A. oxyphylla), as a kind of medicine which also be used
      as food, is widely used in East Asian for the treatment of dyspepsia, diarrhea,
      abdominal pain and deficiency cold of spleen and stomach. This study aimed to
      investigate the protective effects of ethanol extract (EE) and its
      dichloromethane fraction (DM) of A. oxyphylla, which are rich in phenolic
      compounds, against CCl4-induced hepatic injury in vitro and in vivo. EE, DM and
      silymarin ameliorated CCl4-induced decrease of cell viability and increase of
      reactive oxygen species (ROS) in HepG2 cells. The CCl4-induced changes of
      glutathione (GSH) and methane dicarboxylic aldehyde (MDA) levels, and the
      decrease of superoxide dismutase (SOD) and catalase (CAT) activities were all
      restored with the pretreatment of EE, DM and silymarin. The results in liver
      injury model in rats showed that EE, DM and silymarin could significant decrease
      the levels of serum aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), alkaline phosphatase (ALP) and total bilirubin than the model group. Liver
      histopathology revealed that EE and DM attenuated the incidence of liver lesions
      triggered by CCl4 intoxication. They also effectively relieved CCl4-induced
      oxidative damage. Western blot analysis indicated NF-E2-related factor (Nrf2)
      pathway played an critical role in the protection of EE and DM against CCl4
      induced oxidative stress. In conclusion, the extracts from A. oxyphylla might be
      used as hepatoprotective agents.

PMID- 28501010
TI  - Detecting and predicting the impact of land use changes on groundwater quality, a
      case study in Northern Kelantan, Malaysia.
AB  - The conversions of forests and grass land to urban and farmland has exerted
      significant changes on terrestrial ecosystems. However, quantifying how these
      changes can affect the quality of water resources is still a challenge for
      hydrologists. Nitrate concentrations can be applied as an indicator to trace the
      link between land use changes and groundwater quality due to their solubility and
      easy transport from their source to the groundwater. In this study, 25year
      records (from 1989 to 2014) of nitrate concentrations are applied to show the
      impact of land use changes on the quality of groundwater in Northern Kelantan,
      Malaysia, where large scale deforestation in recent decades has occurred. The
      results from the integration of time series analysis and geospatial modelling
      revealed that nitrate (NO3-N) concentrations significantly increased with
      approximately 8.1% and 3.89% annually in agricultural and residential wells,
      respectively, over 25years. In 1989 only 1% of the total area had a nitrate value
      greater than 10mg/L; and this value increased sharply to 48% by 2014. The
      significant increase in nitrate was only observed in a shallow aquifer with a
      3.74% annual nitrate increase. Based on the result of the Autoregressive
      Integrated Moving Average (ARIMA) model the nitrate contamination is expected to
      continue to rise by about 2.64% and 3.9% annually until 2030 in agricultural and
      residential areas. The present study develops techniques for detecting and
      predicting the impact of land use changes on environmental parameters as an
      essential step in land and water resource management strategy development.

PMID- 28501011
TI  - Public health and economic risk assessment of waterborne contaminants and
      pathogens in Finland.
AB  - This study shows that a variety of mathematical modeling techniques can be
      applied in a comprehensive assessment of the risks involved in drinking water
      production. In order to track the effects from water sources to the end
      consumers, we employed four models from different fields of study. First, two
      models of the physical environment, which track the movement of harmful
      substances from the sources to the water distribution. Second, a statistical
      quantitative microbial risk assessment (QMRA) to assess the public health risks
      of the consumption of such water. Finally, a regional computable general
      equilibrium (CGE) model to assess the economic effects of increased illnesses. In
      order to substantiate our analysis, we used an illustrative case of a recently
      built artificial recharge system in Southern Finland that provides water for a
      300,000 inhabitant area. We examine the effects of various chemicals and microbes
      separately. Our economic calculations allow for direct effects on labor
      productivity due to absenteeism, increased health care expenditures and indirect
      effects for local businesses. We found that even a considerable risk has no
      notable threat to public health and thus barely measurable economic consequences.
      Any epidemic is likely to spread widely in the urban setting we examined, but is
      also going to be short-lived in both public health and economic terms. Our
      estimate for the ratio of total and direct effects is 1.4, which indicates the
      importance of general equilibrium effects. Furthermore, the total welfare loss is
      2.4 times higher than the initial productivity loss. The major remaining
      uncertainty in the economic assessment is the indirect effects.

PMID- 28501012
TI  - Alkylphenol and phthalate contamination of all sources of greywater from French
      households.
AB  - Despite the importance of domestic wastewater, the contribution of greywater to
      both alkylphenol and phthalate pollution is not yet well documented. Likewise,
      the detailed emissions of phthalates and alkylphenols by greywater have been
      insufficiently studied, this work aims to fill this gap. The levels of four
      phthalates (DEP, DnBP, BBP and DEHP) and two alkylphenols (nonylphenol isomers
      and octylphenol) were quantified in six different types of greywater, namely that
      from washing machines, manual dishwashing, dishwashers, bathroom water (from
      showers and sinks) and floor cleaning. This paper presents the methodology used
      to characterize all sources of greywater and provides their levels of
      contamination. The highest concentrations were found in greywater produced by the
      washing machine and floor cleaning, while washing machine and shower greywater
      have the highest phthalate and alkylphenol loads because of the volume associated
      with these two sources of greywater.

PMID- 28501013
TI  - Comparison of surface energy budgets and feedbacks to microclimate among
      different land use types in an agro-pastoral ecotone of northern China.
AB  - The biophysical effect of land use conversion plays a significant role in
      regulating climate change. Owing to albedo and evapotranspiration (ET) change,
      the effect of energy budget difference on land surface temperature (LST) is
      important but unclear among contrasting land use types, especially in temperate
      semi-arid regions. Based on moderate-resolution imaging spectroradiometer (MODIS)
      data, we compared the differences in albedo, ET, and LST between cropland and
      grassland (CR-GR), and between planted forest and grassland (PF-GR) in the Horqin
      Sandy Land of Inner Mongolia, an agro-pastoral ecotone of northern China. Our
      main objective was to explore the magnitude and direction of albedo and ET change
      during the growing season and, subsequently, to estimate the biophysical effects
      on LST as a result of land use and land cover change. Our results indicate no
      significant difference in mean monthly albedo for CR-GR and PF-GR. Cropland lost
      more water through ET and significantly decreased daytime LST compared with
      grassland from July to September, but no significant differences in ET and LST
      were observed for PF-GR in any month. The biophysical climate effects were more
      pronounced for CR-GR compared with PF-GR. The response of LST to the changes in
      energy budget confirmed that ET was the critical driving factor relative to
      albedo. Compared with grassland, cropland and planted forest tended to cool the
      land surface by 5.15 degrees C and 1.51 degrees C during the growing season,
      respectively, because of the biophysical effects. Our findings suggest the
      significance of local-scale biophysical effect on climate variation after land
      use conversion in semi-arid regions.

PMID- 28501014
TI  - Discrimination between acute and chronic decline of Central European forests
      using map algebra of the growth condition and forest biomass fuzzy sets: A case
      study.
AB  - Forest decline is either caused by damage or else by vulnerability due to
      unfavourable growth conditions or due to unnatural silvicultural systems. Here,
      we assess forest decline in the Czech Republic (Central Europe) using fuzzy
      functions, fuzzy sets and fuzzy rating of ecosystem properties over a 1*1km grid.
      The model was divided into fuzzy functions of the abiotic predictors of growth
      conditions (Fpred including temperature, precipitation, acid deposition, soil
      data and relative site insolation) and forest biomass receptors (Frec including
      remote sensing data, density and volume of aboveground biomass, and surface humus
      chemical data). Fuzzy functions were designed at the limits of unfavourable,
      undetermined or favourable effects on the forest ecosystem health status. Fuzzy
      sets were distinguished through similarity in a particular membership of the
      properties at the limits of the forest status margins. Fuzzy rating was obtained
      from the least difference of Fpred-Frec. Unfavourable Fpred within unfavourable
      Frec indicated chronic damage, favourable Fpred within unfavourable Frec
      indicated acute damage, and unfavourable Fpred within favourable Frec indicated
      vulnerability. The model in the 1*1km grid was validated through spatial
      intersection with a point field of uniform forest stands. Favourable status was
      characterised by soil base saturation (BS)>50%, BCC/Al>1, Corg>1%, MgO>6g/kg, and
      nitrogen deposition<1200mol(H+)/ha.year. Vulnerable forests had BShumus 46-60%,
      BCC/Al 9-20 and NDVI~0.42. Chronic forest damage occurs in areas with low
      temperatures, high nitrogen deposition, and low soil BS and Corg levels. In the
      Czech Republic, 10% of forests were considered non-damaged and 77% vulnerable,
      with damage considered acute in 7% of forests and chronic in 5%. The fuzzy model
      used suggests that improvement in forest health will depend on decreasing
      environmental load and restoration concordance between growth conditions and tree
      species composition.

PMID- 28501015
TI  - Effect of medium-pressure UV-lamp treatment on disinfection by-products in
      chlorinated seawater swimming pool waters.
AB  - Several brominated disinfection by-products (DBPs) are formed in chlorinated
      seawater pools, due to the high concentration of bromide in seawater. UV
      irradiation is increasingly employed in freshwater pools, because UV treatment
      photodegrades harmful chloramines. However, in freshwater pools it has been
      reported that post-UV chlorination promotes the formation of other DBPs. To date,
      UV-based processes have not been investigated for DBPs in seawater pools. In this
      study, the effects of UV, followed by chlorination, on the concentration of three
      groups of DBPs were investigated in laboratory batch experiments using a medium
      pressure UV lamp. Chlorine consumption increased following post-UV chlorination,
      most likely because UV irradiation degraded organic matter in the pool samples to
      more chlorine-reactive organic matter. Haloacetic acid (HAA) concentrations
      decreased significantly, due to photo-degradation, but the concentrations of
      trihalomethanes (THMs) and haloacetonitriles (HANs) increased with post-UV
      chlorination. Bromine incorporation in HAAs was significantly higher in the
      control samples chlorinated without UV irradiation but decreased significantly
      with UV treatment. Bromine incorporation was promoted in THM and HAN after UV and
      chlorine treatment. Overall, the accumulated bromine incorporation level in DBPs
      remained essentially unchanged in comparison with the control samples. Toxicity
      estimates increased with single-dose UV and chlorination, mainly due to increased
      HAN concentrations. However, brominated HANs are known in the literature to
      degrade following further UV treatment.

PMID- 28501016
TI  - Role of climate anomalies on decadal variation in the occurrence of wintertime
      haze in the Yangtze River Delta, China.
AB  - The wintertime haze day (HD) in the Yangtze River Delta (YRD) region of China
      shows a significant upward trend during the past decades due to the rapid
      industrialization and urbanization. Besides the enhanced anthropogenic emission,
      climate change also plays the important role in the long term HD variations. In
      this study, the significant decadal variation of wintertime HD during the period
      1960-2012 in YRD is examined by the empirical orthogonal function (EOF) analysis,
      featured as less HD occurrence before 1980 and more occurrence after 2000. The
      numerical simulations by the global transport and chemical model (Model for Ozone
      and Related chemical Tracers, MOZART) with the same emission inventory suggest
      8.4% enhancement of wintertime PM2.5 (particulate matter with the equivalent
      diameter of air dynamics less than or equal to 2.5MUm) mass concentration in YRD
      during 2001-2009 compared with that during 1971-1979 attributed to meteorological
      changes, indicating the significant effect of climate anomaly on the decadal
      variations of wintertime HD. Through the composite analysis on the atmospheric
      dynamical and thermal conditions based on the reanalysis data, the faster warming
      in the lower and middle troposphere over the continent in the recent decade is
      suggested to be important for the out-of-phase decadal HD variation in YRD. The
      thermal anomaly not only reverses the zonal thermal difference of land-sea to
      stimulate the anomalous southerlies over YRD leading to reduced prevailing north
      wind in winter, but also develops the deep inversion below the mid-troposphere to
      enhance the atmospheric stability. As a result, more frequent and persistent air
      stagnations in recent decade are expected for the reduction of atmospheric
      horizontal dispersion and vertical diffusion capacity leading to more occurrence
      of wintertime HD in YRD.

PMID- 28501017
TI  - Golgi-independent routes support protein disulfide isomerase externalization in
      vascular smooth muscle cells.
AB  - Extracellular pools of intracellular molecular chaperones are increasingly
      evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox
      chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and
      vascular remodeling, while PDI externalization routes remain elusive. In
      endothelial cells, vesicular-type PDI secretion involves classical and
      unconventional pathways, while in platelets PDI exocytosis involves actin
      cytoskeleton. However, little is known about pecPDI in vascular smooth muscle
      cells(VSMC). Here, we showed that VSMC display a robust cell-surface(cs) PDI
      pool, which binds to cs independently of electrostatic forces. However,
      contrarily to other cells, soluble secreted PDI pool was undetectable in VSMC.
      Calcium ionophore A23187 and TNFalpha enhanced VSMC csPDI. Furthermore, VSMC PDI
      externalization occurred via Golgi-bypass unconventional route, which was
      independent of cytoskeleton or lysosomes. Secreted PDI was absent in ex vivo wild
      type mice aortas but markedly enhanced in PDI-overexpressing mice. Such
      characterization of VSMC pecPDI reinforces cell-type and context specific routes
      of PDI externalization.

PMID- 28501018
TI  - Geographic mobility and potential bridging for sexually transmitted infections in
      Agbogbloshie, Ghana.
AB  - Short-term mobility can significantly influence the spread of infectious disease.
      In order for mobile individuals to geographically spread sexually transmitted
      infections (STIs), individuals must engage in sexual acts with different partners
      in two places within a short time. In this study, we considered the potential of
      mobile individuals as bridge populations - individuals who link otherwise
      disconnected sexual networks and contributed to ongoing STI transmission. Using
      monthly retrospective panel data, we examined associations between short-term
      mobility and sexual partner concurrency in Agbogbloshie, Ghana. We also examined
      bridging by the location of sex acts and the location of sexual partners in
      concurrent triads, and whether mobile individuals from our sample were more
      likely to be members of geographic bridging triads. Although reported rates of
      sexual partnership concurrency were much higher for men compared to women,
      mobility was only associated with increased concurrency for women. Additionally,
      this association held for middle-distance mobility and short-duration trips for
      women. Taking into account the location of sex acts and the location of sexual
      partners, about 22% of men (21.7% and 22.4% for mobile and non-mobile men,
      respectively) and only 3% of women (1.4% and 3.3% for mobile and non-mobile
      women, respectively) were potential bridges for STIs over the last year. Our
      results highlight the gendered nature of mobility and sexual risk behavior,
      reflecting the normative social context that encourages women to conceal certain
      types of sexual behavior.

PMID- 28501019
TI  - Towards a feminist understanding of intersecting violence against women and
      children in the family.
AB  - While intimate partner violence (IPV) against women and violence against children
      (VAC) have emerged as distinct fields of research and programming, a growing
      number of studies demonstrate the extent to which these forms of violence overlap
      in the same households. However, existing knowledge of how and why such co
      occurrence takes place is limited, particularly in the Global South. The current
      study aims to advance empirical and conceptual understanding of intersecting IPV
      and VAC within families in order to inform potential programming. We explore
      shared perceptions and experiences of IPV and VAC using qualitative data
      collected in December 2015 from adults and children in Kampala, Uganda (n = 106).
      We find that the patriarchal family structure creates an environment that
      normalizes many forms of violence, simultaneously infantilizing women and
      reinforcing their subordination (alongside children). Based on participant
      experiences, we identify four potential patterns that suggest how IPV and VAC not
      only co-occur, but more profoundly intersect within the family, triggering cycles
      of emotional and physical abuse: bystander trauma, negative role modeling,
      protection and further victimization, and displaced aggression. The discussion is
      situated within a feminist analysis, including careful consideration of maternal
      violence and an emphasis on the ways in which gender and power dynamics can
      coalesce and contribute to intra-family violence.

PMID- 28501021
TI  - The application of a feedback-informed approach in psychological service with
      youth: Systematic review and meta-analysis.
AB  - Research with adults has consistently demonstrated that the use of regular client
      feedback in psychological services can improve outcomes. However, there appear to
      be fewer studies with youth. The purpose of the current review was to
      explore/assess (1) current developments in research on the use of feedback
      informed approaches in mental health interventions or services for youth 10
      19years of age; (2) the efficacy of client feedback in youth treatment settings;
      and (3) consider future directions for research. A total of 12 studies were
      included in this review, comprising a meta-analysis (n=9) and a qualitative
      review (n=3). Most studies assessed the benefits of a feedback framework in terms
      of symptom severity, functioning levels and/or goal attainments in therapy (i.e.,
      ratings on the feedback-informed tools). The Hedges's g indexes of 0.20 (for
      independent-groups trials), 0.32 (single-group trials) and 0.28 (for all trials)
      suggest that the collection and application of continuous feedback from youth
      clients throughout the course of the interventions/services can boost and produce
      beneficial outcomes for the youth, while noting the feedback effect to be in the
      small range. Based on these initial findings, implications for future research
      and clinical practice are discussed, including considering fruitful research
      directions.

PMID- 28501020
TI  - Educational gains in cause-specific mortality: Accounting for cognitive ability
      and family-level confounders using propensity score weighting.
AB  - A negative educational gradient has been found for many causes of death. This
      association may be partly explained by confounding factors that affect both
      educational attainment and mortality. We correct the cause-specific educational
      gradient for observed individual background and unobserved family factors using
      an innovative method based on months lost due to a specific cause of death re
      weighted by the probability of attaining a higher educational level. We use data
      on men with brothers from the Swedish Military Conscription Registry (1951-1983),
      linked to administrative registers. This dataset of some 700,000 men allows us to
      distinguish between five education levels and many causes of death. The empirical
      results reveal that raising the educational level from primary to tertiary would
      result in an additional 20 months of survival between ages 18 and 63. This
      improvement in mortality is mainly attributable to fewer deaths from external
      causes. The highly educated gain more than nine months due to the reduction in
      deaths from external causes, but gain only two months due to the reduction in
      cancer mortality and four months due to the reduction in cardiovascular
      mortality. Ignoring confounding would lead to an underestimation of the gains by
      educational attainment, especially for the less educated. Our results imply that
      if the education distribution of 50,000 Swedish men from the 1951 cohort were
      replaced with that of the corresponding 1983 cohort, 22% of the person-years that
      were lost to death between ages 18 and 63 would have been saved for this cohort.

PMID- 28501022
TI  - Sociodemographic profile of an Olympic team.
AB  - OBJECTIVES: To document the distribution of sociodemographic markers (race and
      relative access to wealth) in athletes participating at the summer and Winter
      Olympic Games (OGs). STUDY DESIGN: Cross-sectional descriptive epidemiological
      study. METHODS: Sociodemographic data were collected from publically available
      resources for all athletes representing four countries (Canada, United States of
      America, Great Britain and Australia) at the 2014 Sochi Winter OGs and 2016 Rio
      Summer OGs. The prevalence of white and privately educated athletes were
      identified for each sport, country, and team with consideration and comparison to
      the general population. Access indices (i.e. the combined race socio-economic
      access index [CAI]) were developed to describe the relative distribution of white
      and privately educated athletes representing each sport, country and team
      compared to the respective general population. RESULTS: A total of 568 winter and
      1643 summer athletes were included in this study. Privately educated athletes
      constituted 30.3% and 32.7% of winter and summer athletes, respectively; while
      94.9% of winter and 81.7% of summer athletes were white. The CAIs of the
      Canadian, American, British and Australian winter Olympic teams were 0.52, 0.42,
      0.61 and 0.45, respectively. The CAIs, for the Canadian, American, British and
      Australian summer Olympic teams were 0.89, 1.13, 0.82 and 0.83, respectively.
      Summer and winter sports with the greatest and least racial and socio-economic
      biases were identified. CONCLUSION: Racial and socio-economic biases were
      identified in both summer and winter Olympic sports; predominantly favouring
      white and privately educated Olympic athletes. These findings prompt further
      inquiry into barriers for sport-specific participation and advancement, in
      addition to the practice of providing substantial public resources in support for
      Olympic sports and athletes.

PMID- 28501023
TI  - Force-velocity relationship of leg muscles assessed with motorized treadmill
      tests: Two-velocity method.
AB  - Linear regression models applied on force (F) and velocity (V) data obtained from
      loaded multi-joint functional movement tasks have often been used to assess
      mechanical capacities of the tested muscles. The present study aimed to explore
      the properties of the F-V relationship of leg muscles exerting the maximum
      pulling F at a wide range of V on a standard motorized treadmill. Young and
      physically active male and female subjects (N=13+15) were tested on their maximum
      pulling F exerted horizontally while walking or running on a treadmill set to 8
      different velocities (1.4-3.3m/s). Both the individual (median R=0.935) and
      averaged across the subjects F-V relationships (R=0.994) proved to be
      approximately linear and exceptionally strong, while their parameters depicting
      the leg muscle capacities for producing maximum F, V, and power (P; proportional
      to the product of F and V) were highly reliable (0.84<ICC<0.97). In addition, the
      same F-V relationship parameters obtained from only the highest and lowest
      treadmill V (i.e., the 'two-velocity method') revealed a strong relationship
      (0.89<R<0.99), and there were no meaningful differences regarding the magnitudes
      of the same parameters obtained from all 8 V's of the treadmill. We conclude that
      the F-V relationship of leg muscles tested through a wide range of treadmill V
      could be strong, linear, and reliable. Moreover, the relatively quick and fatigue
      free two-velocity method could provide reliable and ecologically valid indices of
      F, V, and P producing capacities of leg muscles and, therefore, should be
      considered for future routine testing.

PMID- 28501024
TI  - Sensing of molecular patterns through cell surface immune receptors.
AB  - In plants, sensing of Pathogen/Microbe-Associated Molecular Patterns
      (PAMPs/MAMPs) and host-derived Damage-Associated Molecular Patterns (DAMPs) by
      host cell surface Pattern Recognition Receptors (PRRs) activates Pattern
      Triggered Immunity (PTI). The identification of an increasing number of
      immunogenic patterns and PRRs illustrates that PTI is a universal defence
      mechanism against pathogens, pests, and parasitic plants, and that evolutionary
      selective pressure drives diversification of molecular patterns and diversity of
      PRRs. Further advances unravelled how some prototypical PRRs get activated to
      initiate metabolic adaptation and defence responses that stop invaders. Deeper
      insights into the repertoire of PRRs will reveal how plants manage to mount
      appropriate defence against diverse kinds of invaders and how we can
      biotechnologically exploit nature's design for sustainable agriculture.

PMID- 28501025
TI  - Effects of unintentional PCBs in pigments and chemical products on
      transcriptional activity via aryl hydrocarbon and nuclear hormone receptors.
AB  - In recent years, some pigments and chemical products have been reported to
      contain polychlorinated biphenyl (PCB) congeners as unintentional byproducts, and
      these have also been detected in residential environments from indoor air and
      house dust. In this study, using in vitro reporter gene assays, we characterized
      the agonistic and antagonistic activities of a total of 25 PCB congeners
      contained in pigments (PCB-1 to -16, -20, -35, -40, -52, -56, -77, -101, -126,
      and -153) against five nuclear hormone receptors, (estrogen receptor (ER)
      alpha/beta, glucocorticoid receptor (GR), androgen receptor (AR), thyroid hormone
      receptor (TR) alpha1) and aryl hydrocarbon receptor (AhR). In the ERalpha/beta
      assays, 19 and 13 of the 25 PCBs tested showed ERalpha/beta agonistic and/or
      antagonistic activities, respectively. Relatively potent agonistic activities
      against ERalpha/beta were found in PCB congeners possessing chlorides at
      positions 2 and 3. In the GR and AR assays, five and all of the 25 PCB congeners
      showed antagonistic activity, respectively. Among the anti-androgenic PCB
      congeners, the activities were more potent in PCB congeners possessing more than
      three chlorides including consecutive ortho- and meta- or meta- and para
      chlorides. In the AhR assay using a sensitive DR-EcoScreen cell line, five of the
      25 PCB congeners showed agonistic activity. We newly found that PCB-1, -35 and 
      56 can act as AhR agonists. Despite these activities among the PCBs, the effects
      of PCB-11, mainly detected in pigments and chemical products, against these
      receptors were found to be weaker than those of other tested PCBs. These results
      suggest that unintentional PCBs in pigments and chemical products might act as
      agonists and/or antagonists against ERalpha/beta, AR, GR, and AhR, and some of
      the PCBs might disrupt endocrine functions via multiple receptors and/or
      simultaneously induce dioxin-like activity via AhR.

PMID- 28501026
TI  - Metabolically speaking: Possible reasons behind the tolerance of 'Sugar Belle'
      mandarin hybrid to huanglongbing.
AB  - Huanglongbing (HLB) is currently considered the most destructive disease of
      citrus. Since its spread to the Americas, HLB has killed millions of trees and
      caused a sharp decline in production in many citrus growing regions. With the
      continuous spread of HLB disease in Florida and worldwide, there is an urgent
      need for the development of commercial citrus cultivars with a strong tolerance
      to HLB. Interestingly, field observations showed that some of the recently
      released mandarin hybrids such as 'Sugar Belle' were tolerant to HLB. In this
      study, we investigated the volatile and non-volatile metabolites of greenhouse
      grown 'Sugar Belle' mandarin and four of its ancestors in order to understand why
      'Sugar Belle' mandarin is relatively tolerant to HLB. Leaf volatiles were
      directly extracted with hexane and analyzed using gas chromatography-mass
      spectrometry (GC-MS). Leaf polar metabolites were extracted with a mixture of
      methanol:water (1:1, v/v), derivatized to their trimethylsilyl ethers, and
      analyzed using GC-MS. Forty-seven volatile compounds and forty-two polar
      metabolites were detected in 'Sugar Belle' mandarin leaves and its ancestors.
      'Sugar Belle' was high in several volatiles such as alpha-thujene, para-cymene,
      gamma-terpinene, thymol, beta-elemene, and (E)-beta-caryophyllene. Some of these
      volatiles, especially thymol, beta-elemene, and (E)-beta-caryophyllene are known
      for their anti-microbial activity. In addition, 'Sugar Belle' mandarin was the
      highest in synephrine, benzoic acid, ferulic acid, caffeic acid, chiro-inositol,
      fructose, glucose, threonic acid, saccharic acid, and galactaric acid, and the
      second in threonine, malic acid, and myo-inositol compared to the ancestors.
      Phenolic compounds such as benzoic, ferulic, and caffeic acids may act as
      antibacterial agents, whereas others like sugar alcohols may protect 'Sugar
      Belle' mandarin from stress during pathogen attack. The tolerance of 'Sugar
      Belle' and other newly released mandarin hybrids should be further evaluated
      using greenhouse controlled studies. If tolerance of these hybrids is confirmed,
      they could be used to replace the traditionally susceptible cultivars.

PMID- 28501027
TI  - Erratum to: A Single Nucleotide Polymorphism in the FADS1 Gene is Associated with
      Plasma Fatty Acid and Lipid Profiles and Might Explain Gender Difference in Body
      Fat Distribution.

PMID- 28501030
TI  - Public Health Ethics and Conflict of Interests.

PMID- 28501028
TI  - Multicentric Castleman disease of hyaline vascular variant presenting with
      unusual systemic manifestations: a case report.
AB  - BACKGROUND: Castleman disease is a rare lymphoproliferative disorder presenting
      with localized or disseminated lymphadenopathy and systemic manifestations. It
      can be categorized in numerous ways, such as unicentric versus multicentric,
      histopathological variants (hyaline-vascular, plasma cell, and mixed), or
      subtypes based on causative viral infections (human immunodeficiency virus, human
      herpesvirus-8, or Kaposi sarcoma herpesvirus). Presentation ranges from
      asymptomatic to symptoms involving multiple organs. Even though the exact
      mechanism of pathogenesis is unknown, treatment is directed toward possible
      etiologies such as interleukin-6, cluster of differentiation 20, and viral
      agents. CASE PRESENTATION: A 36-year-old Sri Lankan woman presented with
      generalized body swelling and foamy urine of 2 weeks' duration. Examination
      revealed pallor; generalized edema; axillary, cervical, and inguinal
      lymphadenopathy; hypertension; and hepatomegaly. Investigations showed
      bicytopenia, nephrotic range proteinuria with hypoalbuminemia,
      hypogammaglobulinemia, and features of hyaline-vascular type Castleman disease in
      a lymph node biopsy. She was managed with rituximab and had good clinical
      improvement. CONCLUSIONS: Castleman disease has a broad spectrum of clinical
      manifestations, disease pathogeneses, and associations and/or complications.
      Medical professionals need to be familiar with this spectrum because timely
      diagnosis and aggressive targeted therapy are the cornerstones of managing these
      patients.

PMID- 28501031
TI  - [Analysis of the Cochrane Review: Non-medical Prescribing versus Medical
      Prescribing for Acute and Chronic Disease Management in Primary and Secondary
      Care. Cochrane Database Syst Rev. 2016;11:CD011227.]
AB  - In countries with diverse socioeconomic levels, in order to address the health
      care demands, the consideration of a wide array of strategies is needed; among
      these, non-medical prescription can be included. The objective of this revision
      was to ascertain whether non-medical prescription results in comparable clinical
      and patient-related outcomes to medical prescription. This systematic review was
      conducted in compliance with the standard Cochrane methodology. Clinical outcomes
      were compared between prescription carried out by non-medical health
      professionals and doctors, provided that the non-medical health professional
      prescribed with a high degree of autonomy, both in hospital and community
      practice, in countries with low, medium and high socioeconomic level. The review
      included 46 clinical trials, with different designs, with 37 337 participants
      overall. Most studies were based on the management of chronic disease in higher
      income countries, where the evidence supports comparable outcomes for the markers
      of disease relative to high blood pressure (moderate-certainty of evidence),
      diabetes control (high-certainty of evidence); high cholesterol
      (moderatecertainty of evidence), among others. Prescription by pharmacists and
      nurses with different levels of undergraduate, specific and postgraduate
      education could provide comparable outcomes to medical prescription, specifically
      with regards to adherence to therapy, adverse events, overall satisfaction,
      quality of life, and resource utilisation (hospitalisations, visits to the
      emergency department, and consultations). Non-medical prescribers frequently had
      medical support available to facilitate a collaborative practice. With
      appropriate training and support, non-medical prescription by nurses and
      pharmacists can be as effective as when carried out by doctors.

PMID- 28501032
TI  - [Perinatal Outcome in Relation to Chorionicity in Twin Pregnancy].
AB  - INTRODUCTION: The incidence of multiple gestations is increasing worldwide and
      many studies have shown higher perinatal morbidity and mortality rates in
      monochorionic twins compared to dichorionic. The aim of this study was to assess
      the twin population born at a tertiary center and to evaluate the impact of
      chorionicity on perinatal outcomes of twin pregnancies. MATERIAL AND METHODS:
      Retrospective study of all twins born in a tertiary center from January 2004 to
      December 2013. RESULTS: In this period, 1051 twins were born, related to 540
      gestations (26.7% monochorionic; 73.3% dichorionic). There was no statistical
      significant difference between the groups concerning obstetric complications. The
      monochorionic group had a higher incidence of intrauterine growth restriction
      (20.5 vs 11.3%, p < 0.001), lower mean maternal age (29.9 vs 31.9 years, p <
      0.001), lower mean gestational age (33.4 vs 34.3 weeks, p < 0.05) and lower mean
      birth weight (1943 vs 2147 g, p < 0.001). Monochorionic twins had a higher
      incidence of hyaline membrane disease (7 vs 4%, p < 0.05), sepsis (10.3 vs 5.8%,
      p < 0.05) and anemia (9.5 vs 5.4%, p < 0.05). There were no statistical
      significant differences concerning necrotizing enterocolitis,
      intraperiventricular hemorrhage or retinopathy of prematurity. Perinatal
      mortality was higher in the monochorionic group (5.2 vs 2.9%, p < 0.05).
      DISCUSSION: Monochorionic twins represent considerable challenges to both
      obstetricians and neonatologists and should be monitored and delivered at
      tertiary centers. CONCLUSION: Currently gemelarity has a major impact on total
      births. It would be interesting to develop protocols to standardize clinical
      approach to twins.

PMID- 28501033
TI  - The Portuguese Version of the European Deprivation Index: An Instrument to Study
      Health Inequalities.
AB  - INTRODUCTION: Tackling socioeconomic health inequalities is a big public health
      challenge and ecological deprivation indexes are essential instruments to monitor
      and understand them. In Portugal, no standard ecological deprivation index
      exists, contrasting with other countries. We aimed to describe the construction
      of the Portuguese version of a transnational deprivation index, European
      Deprivation Index. MATERIAL AND METHODS: The European Deprivation Index was
      developed under the Townsend theorization of deprivation. Using data from the
      European Union - Statistics on Income and Living Conditions Survey, we obtained
      an indicator of individual deprivation. This indicator became the gold-standard
      variable, based on what we selected the variables at aggregate level (census) to
      be included in the European Deprivation Index, a total of eight. The European
      Deprivation Index was produced for the smallest area unit possible (n = 16 094,
      mean/area = 643 inhabitants) and resulted from the weighted sum of the previous
      variables. It was then classified into quintiles. RESULTS: The first quintile
      (least deprived) comprised 20.9% national population and the fifth quintile (most
      deprived) 18.0%. The European Deprivation Index showed a clear geographic pattern
      - most deprived areas concentrated in the South and in the inner North and Centre
      of the country, and the least deprived areas in the coastal areas of North and
      Centre and in the Algarve. DISCUSSION: The development of the European
      Deprivation Index was grounded on a solid theoretical framework, individual and
      aggregate variables, and on a longitudinal Europe-wide survey allowing its
      replication over the time and in any European country. CONCLUSION: Hopefully, the
      European Deprivation Index will start being employed by those interested in
      better understand health inequalities not only in Portugal but across Europe.

PMID- 28501034
TI  - Differences in the Students' Perceptions on the Teaching of Neuroanatomy in a
      Medical Curriculum Organized by Disciplines and an Integrated Medical Curriculum.
AB  - INTRODUCTION: On the subject of curriculum reform, most European medical schools
      are moving away from an educational approach consisting of discipline-based
      courses to an integrated curriculum. The aim of this study was to compare, in the
      Faculty of Medicine of the University of Porto, Portugal, the teaching of
      neuroanatomy in a medical curriculum organized by disciplines and in an
      integrated medical curriculum. MATERIAL AND METHODS: Two hundred sixty one
      students who completed the Curricular Unit with a discipline-based approach
      (Neuroanatomy) and 202 students who completed it with an integrated approach
      (Morphophysiology of the Nervous System) were asked to complete a questionnaire
      on their perceptions about the Curricular Unit. RESULTS: Our study showed that
      students of the Curricular Unit with a discipline-based approach had higher
      grades and evaluated it higher than students who followed the integrated
      approach. However, it also showed that students' grades had a significant effect
      on the evaluation of the curricular unit, with students with higher grades
      evaluating higher than students with lower grades. Besides, the majority of the
      students of the Curricular Unit with an integrated approach appreciated this
      curriculum model and highlighted as a positive point the successful integration
      of contents covered in the three components of the curricular unit. DISCUSSION:
      The curriculum reform led to the integration of neuroanatomy with other
      disciplines and resulted in a reduction of the teaching hours, a redefinition of
      the syllabus contents and the students' learning objectives, the introduction of
      new educational methods and changes in the evaluation system. CONCLUSION: Our
      study could not prove conclusively the supremacy of one pedagogic approach to
      neuroanatomy over the other. Future initiatives to explore different pedagogical
      models in medical education are needed and should be of major concern to the
      medical faculty.

PMID- 28501036
TI  - Tuberculosis in Liver Transplant Recipients: A Report of Eight Cases During a
      Five Year Period.
AB  - INTRODUCTION: Tuberculosis incidence in Portugal ranged from 20 to 22 cases per
      100 000 inhabitants between 2010 and 2014. Tuberculosis incidence in liver
      transplant recipients is not precisely known, but it is estimated to be higher
      than among the general population. Tuberculosis in liver transplant recipients is
      particularly challenging because of the atypical clinical presentation and side
      effects of the antibacillary drugs and their potential interactions with
      immunosuppressive therapies. MATERIAL AND METHODS: We retrospectively reviewed
      the clinical records of liver transplant recipients with post-transplant
      tuberculosis occurring from January 2010 to December 2014 at a liver
      transplantation unit in Lisbon, Portugal. Demographic data, baseline and clinical
      features, as well as treatment regimen, toxicities and outcomes, were analyzed.
      RESULTS: Among 1005 recipients, active tuberculosis was diagnosed in eight
      patients between January 2010 and December 2014 (frequency = 0.8%). Late onset
      tuberculosis was more frequent than early tuberculosis. Mycobacterium
      tuberculosis complex was isolated from cultures in almost every case (7; 87.5%).
      Extra-pulmonary involvement and disseminated tuberculosis were frequent. Two
      patients developed rejection without allograft loss. Crude mortality was 37.5%,
      with 2 deaths being related to tuberculosis. DISCUSSION: Despite the uncertainty
      regarding treatment duration in liver transplant recipients, disease severity, as
      well as number of active drugs against TB infection, should be taken into
      account. There was a need for a rifampin-free regimen and immunosuppression
      adjustment in patients who experienced acute graf rejection. CONCLUSION: Although
      the number of cases of tuberculosis is low, its post-transplant frequency is
      significant and the observed mortality rate is not to be neglected. The cases of
      hepatotoxicity and graft rejection seen in this case series demonstrate the
      challenges associated with tuberculosis diagnosis in liver transplant recipients
      and management of the interactions between immunosuppressors and rifampin. This
      study strengthens the recommendation of latent tuberculosis infection screening
      and treatment in liver transplant candidates or recipients.

PMID- 28501035
TI  - Motivation to Quit Smoking after Acute Coronary Syndrome.
AB  - INTRODUCTION: Self-Determination Theory explores the process through which a
      person acquires motivation to initiate new behaviours related to health and to
      maintain them over time. This study aimed to determine the overall fit of Self
      Determination Theory Model for Health Behavior to the data obtained from a sample
      of smokers hospitalized with acute coronary syndrome, and to identify the
      predictors of smoking status six months after clinical discharge. MATERIAL AND
      METHODS: The sample included 110 participants, regular smokers, hospitalized due
      to acute coronary syndrome. Questionnaires were administered to assess autonomous
      self-regulation, perceived competence, family support, depressive symptoms and
      meaning in life. Participants were asked if they were currently smokers six
      months after clinical discharge. RESULTS: The results showed that the process
      variables specified by Self-Determination Theory fit the data well. Perceived
      competence predicted abstinence from smoking six months after clinical discharge.
      DISCUSSION: Our findings have similar characteristics to other international
      samples in which Self-Determination Theory models havebeen tested. It is
      important to facilitate perceived competence, as the patients who continue to
      smoke have shorter length of life. CONCLUSION: This study highlights the
      importance of considering clinical interventions based on Self-Determination
      Theory to facilitatesmoking cessation.

PMID- 28501037
TI  - Portuguese Version of the EORTC QLQ-OES18 and QLQ-OG25 for Health-Related Quality
      of Life Assessment.
AB  - INTRODUCTION: Health-related quality of life assessment is increasingly important
      as it can help both clinical research and care for patients, particularly among
      oncological patients. Quality of Life Questionnaire - OES18 (esophageal module)
      and Quality of Life Questionnaire - OG25 (esophagogastric module) are the
      European Organization for Research and Treatment of Cancer modules for the
      evaluation of quality of life in patients with esophageal and esophagogastric
      cancers, respectively. The aim of our study was to translate, to culturally adapt
      and to perform a pilot testing to create the Portuguese version of both
      questionnaires. MATERIAL AND METHODS: The European Organization for Research and
      Treatment of Cancer guidelines were followed for translation, cultural adaptation
      and pilot testing of Quality of Life Questionnaire - OES18 (esophageal module)
      and Quality of Life Questionnaire - OG25 (esophagogastric module). The Quality of
      Life Questionnaire - OG25 (esophagogastric module) went through a process of
      forward (English -> Portuguese) and backward (Portuguese -> English) translation,
      by independent native speaker translators. After review, a preliminary version
      was created to be pilot tested among Portuguese patients. As a Brazilian version
      was already available for Quality of Life Questionnaire - OES18 (esophageal
      module), the questionnaire was simply culturally adapted and pilot tested. Both
      cancer and non-cancer patients were included. RESULTS: Overall, 30 patients
      completed the Portuguese version of each questionnaire. Afterwards, a structured
      interview was conducted to find and report any problematic items. Troublesome
      items and wording were changed according to the pilot testing results. The final
      versions were sent to the European Organisation for Research and Treatment of
      Cancer Quality of Life Group and approved. CONCLUSION: The Portuguese versions of
      the European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire - OES18 (esophageal module) and OG25 (esophagogastric module)
      questionnaires are useful, reliable and valid tools for measuring health-related
      quality of life in patients with esophageal and esophagogastric cancers,
      respectively. They can now be used in clinical setting and for scientific
      purposes.

PMID- 28501039
TI  - Symptomatic Control in End-of-Life Patients.
AB  - End-of-life patients present a variety of symptoms that cause suffering for them
      and their respective families. Health professionals throughout their university,
      internship and medical careers are ill-prepared to manage and improve the quality
      of life of these patients. This article aims to provide basic skills in the
      symptomatic management of end-of-life patients, focusing in particular on the
      control of pain, dyspnoea, fatigue, nausea, vomiting and anorexia. It also aims
      to draw attention to basic concepts of control concerning refractory symptoms and
      palliative sedation.

PMID- 28501038
TI  - [Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with
      Other Diagnostic Imaging Modalities].
AB  - INTRODUCTION: The 18F-NaF positron emission tomography/computed tomography is
      being considered as an excellent imaging modality for bone metastases detection.
      This ability was compared with other imaging techniques. MATERIAL AND METHODS: We
      retrospectively evaluated 114 patients who underwent 18F-NaF positron emission
      tomography/ computed tomography. Of these, 49 patients also had bone
      scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10
      18F-FCH positron emission tomography/computed tomography. We identified the
      technique that detected the largest number of bone metastases. For the detection
      of skeletal metastases with the 18F-NaF positron emission tomography/computed
      tomography study, the contribution of the positron emission tomography component
      was compared with the contribution of the computed tomography component. Cases in
      which 18F-NaF positron emission tomography/computed tomography and bone
      scintigraphy required further additional tests for diagnosis clarification were
      registered. RESULTS: The 18F-NaF positron emission tomography/computed tomography
      was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was
      superior to 18F-FDG positron emission tomography/computed tomography in 59% of
      the patients (p < 0.001) and it was superior to 18F-FCH positron emission
      tomography/computed tomography in 40% of the patients (p < 0.001). None of the
      compared imaging techniques were superior to 18F-NaF positron emission
      tomography/computed tomography. The positron emission tomography component was
      superior to computed tomography in 35% of the cases (p < 0.001). Further
      investigation was suggested in only 3.5% of patients who underwent 18F-NaF
      positron emission tomography/computed tomography (45% for bone scintigraphy) (p <
      0.001). DISCUSSION: As with other authors, our experience also confirms that 18F
      NaF positron emission tomography/computed tomography is an excellent imaging
      modality for the detection of bone metastases, detecting lesions in more patients
      and more lesions per patient. CONCLUSION: The 18F-NaF positron emission
      tomography/computed tomography showed a superior ability for the detection of
      bone metastases when compared with bone scintigraphy, 18F-FDG positron emission
      tomography/computed tomography and 18F-FCH positron emission tomography/computed
      tomography.

PMID- 28501040
TI  - [The Relationship Between Immunodepression and the Development of Skin Cancer].
AB  - The effects of immunodepression on several disease states have constituted an
      important area of research, leading to the identification of relevant
      associations between immunodepression and a vast set of comorbidities, including
      infectious diseases, cardiovascular diseases and cancer. Research on the effects
      of immunodepression has mostly been conducted in individuals under
      immunodepression by the human immunodeficiency virus and transplant recipients
      under pharmacological immunosuppression, due to the difficulties in obtaining
      relevant samples sizes in other contexts of immunodepression. Overall,
      immunosuppressed individuals tend to show increased incidence of malignancies,
      but only transplant recipients show significantly increased incidence of skin
      cancer; human immunodeficiency virus-infected individuals only show increased
      incidence of malignancies of infectious origin. This paper presents a literature
      review on the effects of immunodepression in the development of tumours in
      humans, with special emphasis on the development of the different types of skin
      cancer.

PMID- 28501041
TI  - Trauma Patient with Fat Embolism Detected on Computed Tomography.
AB  - Fat embolism is frequent following fractures of long bones, however the
      development of the clinical syndrome of fat embolism (characterized by
      progressive respiratory distress, mental status depression and petechial rash) is
      rare, but relevant because of its potential severity. We report a case of a
      trauma patient with multiple fractures of the right lower limb in whom an
      emergency computed tomography scan showed fat emboli within the lumen of the
      homolateral common femoral vein. The imaging detection of macroscopic fat emboli
      should alert the clinician to the potential for subsequent fat embolism syndrome.

PMID- 28501042
TI  - Behavior Changes and Gait Unsteadiness: The Value of Imaging and Prompt
      Neurosurgical Intervention.
AB  - Cavernous angiomas are central nervous system malformations. Most common
      manifestations are seizures and acute focal neurological deficits. We present a
      case report of a seventy-one year-old man with a two-month history of behavior
      changes, attention deficit and indifference followed by gait unsteadiness.
      Neuropsychological evaluation showed severe cognitive impairment and executive
      dysfunction. Head computed tomography depicted a supraventricular hydrocephaly.
      Magnetic resonance imaging revealed a small hemorrhage, contiguous to a
      mesencephalic cavernous angioma, obstructing the Sylvius aqueduct, causing
      secondary hydrocephalus. Four months after endoscopic ventriculocisternostomy,
      neuropsychological evaluation showed improvement and the patient regained
      autonomy. Parenchyma cavernous angiomas causing direct hemorrhage and subsequent
      obstruction of the Sylvian aqueduct are uncommon. Sub-acute behavior and mental
      state abnormalities are rare first manifestations of cavernous angioma and
      requires high clinical suspicion for its correct diagnosis. Magnetic resonance
      imaging evaluation is crucial in the detection of such patients as prompt
      neurosurgical intervention may substantially improve cognitive function.

PMID- 28501043
TI  - Aortic Dissection Mimicking ST Elevation Myocardial Infarction.

PMID- 28501044
TI  - Scrotal Cystocele by Computed Tomography and Ultrasound.

PMID- 28501045
TI  - [Letter to the Editor: Comments to Training and Medical Education].

PMID- 28501046
TI  - Reporting pre-exposure prophylaxis use in Craigslist personal advertisements
      among men seeking sex with men in the United States.
AB  - This study describes the self-reported use of pre-exposure prophylaxis (PrEP) in
      the personal advertisements of men seeking sex with men in the United States on
      the online classified advertisement site, Craigslist. Overall self-reported PrEP
      use was low (0.20%; 95% confidence interval (CI)=0.18-0.22). However, PrEP use in
      personal ads was described in conjunction with seeking sexual risk behaviours
      including 'bareback' sex (22.7%; 95% CI=17.7-27.7%) and sex with substance use
      (26.8%; 95% CI=21.5-32.1%). Only 4.0% of personal ads sought safe sex (3.3%; 95%
      CI=1.2-5.4%) or required condoms (0.7%; 95% CI=-0.3-1.7%). Our findings
      underscore the need for increased public PrEP awareness, particularly among men
      seeking sex with men, as well as the importance of healthcare providers
      emphasising sexually transmissible infection prevention behaviours (i.e. condom
      use) used in conjunction with PrEP.

PMID- 28501047
TI  - Realising the potential of health needs assessments.
AB  - Population-level assessment and planning has traditionally been the role of
      public health departments but in establishing Primary Health Networks (PHNs), the
      Australian Government has instituted a new mechanism for identifying community
      needs and commissioning services to meet those needs. If PHNs are to achieve the
      vision of nimble organisations capable of identifying and addressing local health
      needs via integrated health and social services, several things need to occur.
      First, PHN funding schedules must become more flexible. Second, the Federal
      health department must maintain an open dialogue with PHNs, permit waivers in
      funding schedules to suit local conditions and be prepared to back innovations
      with seed investment. Third, health data exchange and linkage must be accelerated
      to better inform community needs assessments and commissioning. Finally, PHNs
      must be encouraged and supported to develop collaborations both within and
      outside the health sector in order to identify and address a broad set of health
      issues and determinants. By following these principles, PHNs may become leading
      change agents in the Australian healthcare system.

PMID- 28501049
TI  - Distrusting doctors.
AB  - Objective The aim of the present study was to describe how policy makers
      (bureaucrats and politicians) in Australia and Ontario (Canada) perceive evidence
      provided by doctors to substantiate applications for disability income support
      (DIS) by their patients with mental illnesses. Because many mental illnesses
      (e.g. depression) lack diagnostic tests, their existence and effects are more
      difficult to demonstrate than most somatic illnesses.Methods Semi-structured
      interviews were conducted with 45 informants, all influential in the design of
      the assessment of DIS programs. The informants were subcategorised into
      advocates, legal representatives, doctors (general practitioners (GPs) and
      specialists (e.g. psychiatrists)), policy insiders and researchers. Informants
      were found through snowball sampling. Following the principles of grounded
      theory, data collection and analysis occurred in tandem.Results Informants
      expressed some scepticism about doctors' evidence. Informants perceived that
      doctors could, due to lack of diagnostic certainty, 'write these things
      [evidence] however [they] want to'. Psychiatrists, perceived as having more time
      and skills, were considered as providing more trustworthy evidence than
      GPs.Conclusion Doctors, providing evidence to support applications, play an
      important role in determining disability. However, policy makers perceive
      doctors' evidence about mental illnesses as less trustworthy than evidence about
      somatic illnesses. This affects decisions by government adjudicators.What is
      known about the topic? Doctors (GPs and psychiatrists) are often asked to provide
      evidence to substantiate a DIS application for those with mental illnesses. We
      know little about the perception of this evidence by the policy makers who
      consider these applications.What does this paper add? Policy makers distrust
      doctors' evidence in relation to mental illnesses. This is partly because many
      mental illnesses lack diagnostic proof, in contrast with evidence for somatic
      conditions, where the disability is often visible and proven through diagnostic
      tests. Furthermore, GPs' evidence is considered less trustworthy than that of
      psychiatrists.What are the implications for practitioners? Although doctors'
      evidence is often required, the utility of their evidence is limited by policy
      makers' perceptions.

PMID- 28501048
TI  - Systematic review of evidence underpinning non-pharmacological therapies in
      dementia.
AB  - Objective Dementia is one of the most common illnesses worldwide, and is one of
      the most important causes of disability in older people. Currently, dementia
      affects over 35million people around the globe. It is expected that this number
      will increase to 65.7million by 2030. Early detection, diagnosis and treatment to
      control the principal behaviour symptoms may help reduce these numbers and delay
      the progression to more advanced and dangerous stages of this disorder with
      resultant increase quality of life for those affected. The main goal of the
      present systematic literature review was to examine contemporary evidence
      relating to non-pharmacological therapy in the treatment of dementia.Methods To
      achieve the study goal, the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) statement was used.Results This study identified the five
      most common behaviours in patients with dementia as aggression, wandering,
      agitation, apathy and sleep disturbances. Two non-pharmacological therapies were
      the most studied treatment: music therapy and aromatherapy. Ten other non
      pharmacological therapies were also identified, but these lack a sufficient
      evidence-base.Conclusion Although all the therapies identified could be used as
      part of the treatment of behavioural symptoms, there is insufficient evidence
      relating to the indications, appropriate use and effectiveness of these therapies
      to apply in each behavioural treatment. Thus, the present study has demonstrated
      a significant research gap.What is known about the topic? Despite the widespread
      use of many different types of therapies, there is limited evidence regarding the
      efficacy of non-pharmaceutical therapies deployed in the management of behaviours
      of concern manifested by some people who suffer with dementia in all its
      forms.What does this paper add? This systematic review examines contemporary
      evidence from the literature to determine whether there is an evidence base
      available that would underpin the use of these therapies. This report on a PRISMA
      systematic review of the available literature demonstrates that only two
      therapies have some evidence to underpin the use of these non-pharmaceutical
      therapies and that a significant research gap is exists.What are the implications
      for practitioners? The implications for practitioners is that significant
      research effort is required to determine the efficacy of many of the therapies
      that are currently deployed, and thus many of the therapies used lack an evidence
      base at this time.

PMID- 28501050
TI  - Do patients discharged from advanced practice physiotherapy-led clinics re
      present to specialist medical services?
AB  - Objective The aim of the present study was to determine the rates of re-referral
      to specialist out-patient clinics for patients previously managed and discharged
      from an advanced practice physiotherapy-led service in three metropolitan
      hospitals. Methods A retrospective audit was undertaken of 462 patient cases with
      non-urgent musculoskeletal conditions discharged between 1 April 2014 and 30
      March 2015 from three metropolitan hospitals. These patients had been discharged
      from the physiotherapy-led service without requiring specialist medical review.
      Rates and patterns of re-referral to specialist orthopaedic, neurosurgical,
      chronic pain, or rheumatology services within 12 months of discharge were
      investigated. Results Forty-six of the 462 patients (10.0%) who were managed by
      the physiotherapy-led service were re-referred to specialist medical orthopaedic,
      neurosurgical, chronic pain or rheumatology departments within 12 months of
      discharge. Only 22 of these patients (4.8%) were re-referred for the same
      condition as managed previously and discharged. Conclusions Ninety-five per cent
      of patients with non-urgent musculoskeletal conditions managed by an advanced
      practice physiotherapy-led service at three metropolitan hospitals did not re
      present to access public specialist medical services for the same condition
      within 12 months of discharge. This is the first time that re-presentation rates
      have been reported for patients managed in advanced practice physiotherapy
      services and the findings support the effectiveness of these models of care in
      managing demand for speciality out-patient services. What is known about the
      topic? Advanced practice physiotherapy-led services have been implemented to
      address the needs of patients referred with non-urgent musculoskeletal conditions
      to hospital specialist out-patient services. Although this model is widely used
      in Australia, there has been very little information about whether patients
      managed in these services subsequently re-present for further specialist medical
      care. What does this paper add? This paper identifies that the majority (95%) of
      patients managed by an advanced practice physiotherapy-led service did not re
      present for further medical care for the same condition within 12 months of
      discharge. What are the implications for practitioners? This paper supports the
      use of advanced practice physiotherapy-led services in the management of
      overburdened neurosurgical and orthopaedic specialist out-patient waiting lists.

PMID- 28501051
TI  - 2018: the end of a cycle in Radiologia.

PMID- 28501052
TI  - Self-ligating Brackets May Not Have Clinical Advantages Over Conventional
      Brackets for the Periodontal Health of Adolescent Orthodontic Patients.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effect of bracket ligation on
      the periodontal status of adolescents undergoing orthodontic treatment. A
      systematic review and meta-analysis. Arnold S, Koletsi D, Patcas R, Eliades T. J
      Dent 2016; 54:13-24. SOURCE OF FUNDING: The authors did not report any funding
      source information for the study TYPE OF STUDY/DESIGN: Systematic review with
      meta-analysis of data.

PMID- 28501053
TI  - The Risk of Medication-Related Osteonecrosis of the Jaw After Dental Extraction
      is Higher for Patients on Intravenous as Compared With Oral Antiresorptive Drugs.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Occurrence and risk indicators of
      medication-related osteonecrosis of the jaw after dental extraction: a systematic
      review and meta-analysis. Gaudin E, Seidel L, Bacevic M, Rompen E, Lambert F. J
      Clin Periodontol 2015;42(10):922-32. SOURCE OF FUNDING: Internal institutional
      support TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

PMID- 28501054
TI  - Cement- and Screw-Retained Implant-Supported Restorations Showed Comparable
      Marginal Bone Loss and Implant Survival Rate.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Evaluation of cement-retained versus
      screw-retained implant-supported restorations for marginal bone loss: A
      systematic review and meta-analysis. Lemos CAA, de Souza Batista VE, de Faria
      Almeida DA, Junior JFS, Verri FR, Pellizzer EP. J Prosthet Dent 2016; 115(4):419
      27. SOURCE OF FUNDING: Sao Paulo Research Foundation (FAPESP), grant 2014/02490
      8. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

PMID- 28501055
TI  - Limited Evidence Suggests There Is No Difference Between the Clinical Longevity
      of direct vs Indirect Composite Resins in Class I and II Cavities.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Longevity of direct and indirect
      resin composite restorations in permanent posterior teeth: A systematic review
      and meta-analysis. Da Veiga AMA, Cunha AC, Ferreria DMTP, Fidalgo TK, Chianca TK,
      Reis KR, Maia LC. J Dent 2016;54:1-12. SOURCE OF FUNDING: Federal University of
      Rio de Janeiro, Brazil. This study was conducted as part of the master degree for
      one of the authors under supervision by another author. TYPE OF STUDY/DESIGN:
      Systematic review with meta-analysis.

PMID- 28501056
TI  - Resin Infiltration May Be Considered as a Color-Masking Treatment Option for
      Enamel Development Defects and White Spot Lesions.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Is resin infiltration an effective
      esthetic treatment for enamel development defects and white spot lesions? A
      systematic review. Borges AB, Caneppele TMF, Masterson D, Maia LC. J Dent
      2017;56:11-8. SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN:
      Systematic review.

PMID- 28501057
TI  - Mini Implant-Retained Complete Overdenture Can be an Alternative Treatment Option
      for Selected Patients.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Complete overdentures retained by
      mini implants: A systematic review. Lemos CAA, Verri FR, de Souza Batista VE,
      Santiago JF Jr, Mello CC, Pellizzer EP. J Dent 2017;57:4-13. SOURCE OF FUNDING:
      The authors did not report any external sources of fund. TYPE OF STUDY/DESIGN:
      Systematic review.

PMID- 28501058
TI  - Limited-Quality Evidence Suggests That Early Caries Experience at Age 6 years May
      Predict Low Oral Health-Related Quality of Life at Age 10 years.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Early Caries Predicts Low Oral
      Health-Related Quality of Life at a Later Age. Kragt L, van der Tas JT, Moll HA,
      Elfrink ME, Jaddoe VW, Wolvius EB, Ongkosuwito EM. Caries Res. 2016; 50(5):471-9.
      SOURCE OF FUNDING: This study was funded by (1) the Erasmus Medical Center,
      Rotterdam, the Erasmus University, Rotterdam, (2) the Netherlands Organization
      for Health Research and Development, (3) an unrestricted grant from GABA,
      Therwil, Switzerland, (4) the Netherlands Organization for Health Research and
      Development (VIDI 016.136.361), and a (5) consolidator grant from the European
      Research Council (ERC-2014- CoG-64916). TYPE OF STUDY/DESIGN: Prospective Cohort
      Study.

PMID- 28501059
TI  - Stopping Anticoagulation Therapy Before Implant and Bone Grafting Surgery May Not
      Be Necessary to Prevent Bleeding Events.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Management of anticoagulated
      patients in implant therapy: a clinical comparative study. Clemm R, Neukam FW,
      Rusche B, Bauersachs A, Musazada S, Schmitt CM. Clin Oral Implants Res
      2016;27(10):1274-82. SOURCE OF FUNDING: Information not available TYPE OF
      STUDY/DESIGN: Cohort study.

PMID- 28501060
TI  - Analysis of Orange/Red Fluorescence for Bacterial Activity in Initial Carious
      Lesions May Provide Accurate Lesion Activity Assessment for Caries Progression.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Orange/Red Fluorescence of Active
      Caries by Retrospective Quantitative Light-Induced Fluorescence Image Analysis.
      Gomez GF, Eckert GJ, Zandona AF.Caries Res 2016; 50(3):295-302. SOURCE OF
      FUNDING: The study was partially supported by a grant from NIH/NIDCR
      (R01DE017890) TYPE OF STUDY/DESIGN: Retrospective case-control design using the
      data collected in a longitudinal study.

PMID- 28501061
TI  - Limited Evidence Shows That a Motivational Interviewing Approach May be the Most
      Effective Behavioral Intervention for Reducing Dental Caries in Children.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Preventing childhood caries: a
      review of recent behavioral research. Albino J, Tiwari T. J Dent Res
      2016;95(1):35-42. SOURCE OF FUNDING: Government. NIDCR grants U54DE019259 and
      1K99DE024758-01A1. TYPE OF STUDY/DESIGN: Literature review.

PMID- 28501062
TI  - Systemic Propolis (Adjuvant to Nonsurgical Periodontal Treatment) May aid in
      Glycemic Control and Periodontal Health in Type 2 Diabetes of Long Duration.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Propolis improves periodontal status
      and glycemic control in patients with type 2 DM and chronic periodontitis: A
      randomized clinical trial. El-Sharkawy HM, Anees MM, Van Dyke TE. J Periodontol
      2016;87:1418-1426. SOURCE OF FUNDING: Information not available. TYPE OF
      STUDY/DESIGN: Randomized controlled trial (RCT).

PMID- 28501063
TI  - Case Selection is Critical for Successful Outcomes Following Immediate Implant
      Placement in the Esthetic Zone.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Immediate versus delayed implant
      placement after anterior single tooth extraction: the timing randomized
      controlled clinical trial. Tonetti MS, Cortellini P, Graziani F, Cairo F, Lang
      NP, Abundo R, Conforti GP, Marquardt S, Rasperini G, Silvestri M, Wallkamm B,
      Wetzel A. Journal of Clinical Periodontology 2017;44(2):215-24. SOURCE OF
      FUNDING: Nonprofit, Foundations: European Research Group on Periodontology,
      Genova, Italy Industry: Thommen Medical AG, Switzerland and Geistlich AG,
      Switzerland (biomaterials). TYPE OF STUDY/DESIGN: Randomized controlled trial.

PMID- 28501064
TI  - Four or More Amalgam Fillings Correlate With Higher Blood Mercury Levels in
      Pregnant Women but Not High Enough to be of Health Concern.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Dental associations with blood
      mercury in pregnant women. Golding J, Steer CD, Gregory S, Lowery T, Hibbeln JR,
      Taylor CM. Community Dent Oral Epidemiol 2016; 44: 216-22. SOURCE OF FUNDING:
      This study was funded by a combination of government (UK Medical Research
      Council), foundation/nonprofit (the Welcome Trust) and university (University of
      Bristol, UK) grants. TYPE OF STUDY/DESIGN: Cross-sectional.

PMID- 28501065
TI  - Limited and Nongeneralizable Evidence Shows Neighborhood Contextual Factors May
      Be Linked to Dental Treatment but Not Untreated Caries Prevalence.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Neighbourhood Determinants of Caries
      Experience in Preschool Children: A Multilevel Study. Priesnitz MC, Celeste RK,
      Pereira MJ, Pires CA, Feldens CA, Kramer PF. Caries Res 2016;50(5):455-61. SOURCE
      OF FUNDING: None. TYPE OF STUDY/DESIGN: Cross-sectional study.

PMID- 28501066
TI  - Taxing Sugary Beverages Reduces Their Purchase, Especially Among Poor Households.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Beverage purchases from stores in
      Mexico under the excise tax on sugar sweetened beverages: observational study.
      Colchera MA, Popkin BM, Rivera JA, Ng SW. Br Med J 2016;352:h6704. SOURCE OF
      FUNDING: Bloomberg Philanthropies, Robert Wood Johnson Foundation, Instituto
      Nacional de Salud Publica and Carolina Population Center. TYPE OF STUDY/DESIGN:
      Observational study.

PMID- 28501067
TI  - In Defense of Flossing: Can We Agree It's Premature to Claim Flossing is
      Ineffective to Prevent Dental Caries?
AB  - Current evidence pertaining to the effectiveness of flossing and caries
      prevention is potentially being misinterpreted by health oversight bodies, which
      may have significant implications for current and future public flossing
      guidelines. We identify and discuss several methodological deficiencies,
      including the lack of validated measures of flossing skill, over-reliance on self
      reported flossing behavior, and the lack of current guidelines on how to
      interpret and apply evidence-based findings to specific clinical scenarios that
      are present in the studies of flossing effectiveness included in the Cochrane
      Review. As such, we argue that it is premature for health oversight bodies to
      conclude that flossing is ineffective in the prevention of dental caries. Our
      research group, which is funded by the National Institutes of Health (NIH), is
      developing a valid and reliable provider-observed measure of tooth brushing and
      flossing skill that may help promote higher quality flossing evidence in the
      future.

PMID- 28501068
TI  - Preliminary Evidence for the Complete Digital Esthetic Rehabilitation Treatment:
      Case Report and 1-Year Follow-up.
AB  - PURPOSE: To show through computer-aided design and manufacturing technology
      combined with novel digital acquisition images and the right restorative material
      that the technology can provide an easier and predictable workflow for general
      practitioners. BASIC PROCEDURE: This case report presents a fully digital
      treatment of a 59-year-old patient with tooth-supported crowns and provides a
      detailed step-by-step digital technique to obtain a successful result.
      CONCLUSION: By avoiding traditional impression and fixed prosthetic techniques,
      excellent clinical results can be obtained, minimizing the required steps and
      simplifying the overall procedure. This adds information to the current
      literature, allowing general practitioners to choose the best treatment option.
      The function and esthetics remained unaltered over a 1-year follow-up period. No
      fracture or decementation was observed.

PMID- 28501069
TI  - Emergency Department Utilization related to dental conditions and distribution of
      Dentists, Nebraska 2011-2013.
AB  - PURPOSE: This study aims to provide estimates of hospital-based emergency
      department (ED) visits due to dental conditions in Nebraska and to examine
      patient-related characteristics associated with ED charges. In addition, this
      study provides dental-related ED visits and distribution of dentists by county.
      METHODS: For the study, we used the State Emergency Department Database for
      Nebraska for the years 2011 through 2013 and the Health Resources and Services
      Administration's Area Health Resource File. All ED visits with dental conditions
      in Nebraska were selected. The primary outcome variable was hospital-based ED
      charges. Multivariable linear regression model was used to examine the effects of
      patient-related factors on ED charges. RESULTS: During the study period, a total
      of 9943 dental-related ED visits occurred. Of these, 55.5% patients aged between
      25 and 44 years. Thirty-nine percent of all dental ED visits had patients who
      were self-financed or uninsured. Twenty counties in Nebraska do not have a
      dentist, and nine counties had more than 50 ED visits per 10,000 population.
      Patients residing in urban areas paid significantly higher charges than those
      living in rural towns, small rural towns, or isolated rural areas. The mean and
      total ED charges attributed to dental conditions for the entire study period were
      $934 and $9.3 million, respectively. CONCLUSION: Patients who are uninsured, aged
      25-44 years, covered by private insurance, and residing in urban areas are
      identified to be at high risk. There is a need to develop health policies and
      programs to improve access to dental care in rural states.

PMID- 28501070
TI  - Use of Evidence-Based Decision-Making in Comprehensive Dental Treatment of a
      Patient with Meth Mouth-A Case Report.
AB  - OBJECTIVE: This case report illustrates the use of evidence-based practice in
      formulating a comprehensive dental treatment plan for a patient who presented
      himself with signs of oral health debilitation accompanying methamphetamine (MA)
      abuse called "meth mouth" with the goal of providing dental care practitioners in
      Saudi Arabia with an insight into the global problem of MA abuse and its impact
      on oral health. BACKGROUND: This report documents the case of a 22-year-old male
      patient who reported to the clinic with rampant caries caused due to MA abuse
      exacerbated by poor oral hygiene and smoking habit. METHOD: The treatment plan of
      this present case was formulated on the lines of the evidence-based dentistry
      approach. A clinical question was composed based on the Problem, Intervention,
      Comparison, and Outcome format to identify past studies and case reports on meth
      mouth. A standard search was conducted on PubMed Central. Standard guidelines on
      the treatment of meth mouth were extracted from the Web site of the American
      Dental Association. RESULTS: A total of 2 systematic reviews, 7 review articles,
      4 epidemiologic studies, 5 case reports, and 1 American Dental Association
      guideline were found. CONCLUSION: Accelerated dental decay leading to rampant
      caries in young and middle-aged adults is a characteristic oral finding in MA
      abusers. The most important factor that affects the prognosis of dental care is
      complete cessation of MA use by the patient.

PMID- 28501072
TI  - Letter to the Editor.

PMID- 28501071
TI  - In Patients With Symptomatic Irreversible Pulpitis, Articaine is 3.6 Times More
      Efficacious Than Lidocaine in Achieving Anesthetic Success When Used for
      Supplementary Infiltration After Mandibular Block Anesthesia.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Does articaine provide an advantage
      over lidocaine in patients with symptomatic irreversible pulpitis? A systematic
      review and meta-analysis. Kung J, McDonagh M, Sedgley CM. J Endod 2015;
      41(11):1784-94. SOURCE OF FUNDING: The study was supported by the OHSU Department
      of Endodontology Les Morgan Endowment Fund and a resident research grant from the
      American Association of Endodontists Foundation TYPE OF STUDY/DESIGN: Systematic
      review with meta-analysis of data.

PMID- 28501073
TI  - Prophylactic Hemodialysis for Protection Against Gadolinium-Induced Nephrogenic
      Systemic Fibrosis: A Doll's House.

PMID- 28501074
TI  - Scared to the Marrow: Pitfalls and Pearls in Renal Imaging.

PMID- 28501075
TI  - Gadolinium Retention and Toxicity-An Update.
AB  - Until 2006, the main considerations regarding safety for all gadolinium-based
      contrast agents (GBCAs) were related to short-term adverse reactions. However,
      the administration of certain "high-risk" GBCAs to patients with renal failure
      resulted in multiple reported cases of nephrogenic systemic fibrosis. Findings
      have been reported regarding gadolinium deposition within the body and various
      reports of patients who report suffering from acute and chronic symptoms
      secondary to GBCA's exposure. At the present state of knowledge, it has been
      proved that gadolinium deposits also occur in the brain, irrespective of renal
      function and GBCAs stability class. To date, no definitive clinical findings are
      associated with gadolinium deposition in brain tissue. Gadolinium deposition
      disease is a newly described and probably infrequent entity. Patients presenting
      with gadolinium deposition disease may show signs and symptoms that somewhat
      follows a pattern similar but not identical, and also less severe, to those
      observed in nephrogenic systemic fibrosis. In this review, we will address
      gadolinium toxicity focusing on these 2 recently described concerns.

PMID- 28501076
TI  - Intravenous Contrast: Friend or Foe? A Review on Contrast-Induced Nephropathy.
AB  - Intravenous iodinated contrast is used in many contrasted imaging studies ranging
      from computed tomography to angiography. The risks of contrast-induced
      nephropathy (CIN) and its incidence have not been clearly defined. Most iodinated
      contrast media used today are hypertonic compared with serum osmolality and pose
      biological risks. However, the risk of CIN in the general population may be
      overestimated. Confounding risk factors may contribute to acute kidney injury
      other than attributable risk of contrast exposure. In high-risk populations such
      as in those with CKD, CIN risk may be higher and thus caution should be exerted
      with contrast exposure. The volumes of contrast should be minimized as much as
      possible and hemodynamic status should be optimized before contrast
      administration.

PMID- 28501078
TI  - The Role of PET Scanning in the Evaluation of Patients With Kidney Disease.
AB  - Patients with underlying kidney disease are often required to undergo imaging for
      a variety of purposes including diagnosis and prognosis. A test that is being
      increasingly used with for this group of patients is the positron emission test
      (PET) scan. In addition, combining the nuclear medicine technique (PET) with
      computed tomography scan allows additional imaging advantages over either alone.
      These imaging modalities are commonly used for a number of extrarenal indications
      (ie, cancer, coronary artery disease, central nervous system disease, infectious
      diseases, and others). They have also been used for diagnosis of acute
      tubulointerstitial nephritis, evaluation and management of retroperitoneal
      fibrosis, identifying infection within kidney and liver cysts, and distinguishing
      complex kidney cysts from kidney cancer in patients with underlying CKD. We will
      review PET scan utility in patients with kidney disease.

PMID- 28501077
TI  - Recent Advances in Magnetic Resonance Imaging Assessment of Renal Fibrosis.
AB  - CKD is a global public health problem. Renal fibrosis is a final common pathway
      leading to progressive loss of function in CKD. The degree of renal fibrosis
      predicts the prognosis of CKD. Recent studies have shown that bone marrow-derived
      fibroblasts contribute significantly to the development of renal fibrosis, which
      may yield novel therapeutic strategy for fibrotic kidney disease. Therefore, it
      is imperative to accurately assess the degree of renal fibrosis noninvasively to
      identify those patients who can benefit from antifibrotic therapy. In this
      review, we summarize recent advances in the assessment of renal fibrosis by
      magnetic resonance imaging.

PMID- 28501079
TI  - Functional Magnetic Resonance Imaging of the Kidneys-With and Without Gadolinium
      Based Contrast.
AB  - Assessment of renal function with magnetic resonance imaging (MRI) has been
      actively explored in the past decade. In this review, we introduce the principle
      of MRI and review recent progress of MRI methods (contrast enhanced and
      noncontrast) in assessing renal function. Contrast-enhanced MRI using ultra-low
      dose of gadolinium-based agent has been validated for measuring single-kidney
      glomerular filtration rate and renal plasma flow accurately. For routine
      functional test, contrast-enhanced MRI may not replace the simple serum
      creatinine method. However, for patients with renal diseases, it is often worthy
      to perform MRI to accurately monitor renal function, particularly for the
      diseased kidney. As contrast-enhanced MRI is already an established clinical tool
      for characterizing renal structural abnormalities, including renal mass and
      ureteral obstruction, it is possible to adapt the clinical MRI protocol to
      measure single-kidney glomerular filtration rate and renal plasma flow, as
      demonstrated by recent studies. What makes MRI unique is the promise of its
      noncontrast methods. These methods include arterial spin labeling for tissue
      perfusion, blood oxygen-level dependent for blood and tissue oxygenation, and
      diffusion-weighted imaging for water diffusion. For each method, we reviewed
      recent findings and summarized challenges.

PMID- 28501080
TI  - Intravenous Contrast-Induced Nephropathy-The Rise and Fall of a Threatening Idea.
AB  - Contrast-induced nephropathy (CIN) has been considered to be a cause of renal
      failure for over 50 years, but careful review of past and recent studies reveals
      the risks of CIN to be overestimated. Older studies frequently cited the use of
      high-osmolality contrast media, which have since been replaced by low-osmolality
      contrast media, which have lower risks for nephropathy. In addition, literature
      regarding CIN typically describes the incidence following cardiac angiography,
      whereas the risk of CIN from intravenous injection is much lower. Most of the
      early published literature also lacked appropriate control groups to compare to
      those that received iodinated contrast, and thus attributed rises in creatinine
      to intravenous contrast without considering normal creatinine fluctuations
      (frequent in patients with kidney disease) and other acute pathologic states such
      as hypotension or nephrotoxic drug administration. The aim of this paper is to
      review the literature detailing CIN risk, discuss why CIN risk is often
      overestimated and how withholding contrast can lead to misdiagnosis and delay in
      appropriate patient management.

PMID- 28501081
TI  - The Impact of Excess Ligand on the Retention of Nonionic, Linear Gadolinium-Based
      Contrast Agents in Patients With Various Levels of Renal Dysfunction: A Review
      and Simulation Analysis.
AB  - The role of gadolinium (Gd)-based contrast agents (GBCAs) in the pathophysiology
      of nephrogenic systemic fibrosis (NSF) is now uncontested. Although the
      definitive mechanism has not been established, the association with weaker GBCA
      ligands and with reduced renal clearance supports a hypothesis that Gd release
      from the GBCAs is a key process in precipitating the disease. Prevention
      strategies often include the use of more stable GBCA ligands in patients with
      reduced kidney function, but animal models and some clinical data suggest that
      better patient outcomes can be achieved when excess ligand is administered with
      weaker GBCAs; this is particularly significant for OptiMARK, which contains a
      nonionic, linear ligand similar to gadodiamide, the active ingredient in
      Omniscan, but contains twice the amount of excess ligand. Here we review evidence
      regarding the use of OptiMARK over Omniscan for prevention of NSF and perform a
      pharmacokinetic-based simulation to determine if the presented evidence is
      consistent with the established kinetics of GBCAs and Gd.

PMID- 28501083
TI  - The Gastric Microbiome and Its Influence on Gastric Carcinogenesis: Current
      Knowledge and Ongoing Research.
AB  - Gastric malignancies are a leading cause of cancer-related death worldwide. At
      least 2 microbial species are currently linked to carcinogenesis and the
      development of cancer within the human stomach. These include the bacterium
      Helicobacter pylori and the Epstein-Barr virus. In recent years, there has been
      increasing evidence that within the human gastrointestinal tract it is not only
      pathogenic microbes that impact human health but also the corresponding
      autochthonous microbial communities. This article reviews the gastrointestinal
      microbiome as it relates primarily to mechanisms of disease and carcinogenesis
      within the upper gastrointestinal tract.

PMID- 28501082
TI  - A High-Content Screening Technology for Quantitatively Studying Podocyte
      Dynamics.
AB  - Podocytes form the visceral layer of a kidney glomerulus and express a
      characteristic octopus-like cellular architecture specialized for the
      ultrafiltration of blood. The cytoskeletal dynamics and structural elasticity of
      podocytes rely on the self-organization of highly interconnected actin bundles,
      and the maintenance of these features is important for the intact glomerular
      filtration. Development of more differentiated podocytes in culture has
      dramatically increased our understanding of the molecular mechanisms regulating
      podocyte actin dynamics. Podocytes are damaged in a variety of kidney diseases,
      and therapies targeting podocytes are being investigated with increasing efforts.
      Association between podocyte damage and disease severity-or between podocyte
      recovery and the performance of therapeutic molecules-have been the venues of
      research for years. In this perspective, more standardized high--content
      screening has emerged as a powerful tool for visualization and analysis of
      podocyte morphology. This high-throughput fluorescence microscopy technique is
      based on an automated image analysis with simultaneous detection of various
      phenotypes (multiplexing) across multiple phenotypic parameters
      (multiparametric). Here, we review the principles of high-content screening
      technology and summarize efforts to carry out small compound screen using
      podocytes.

PMID- 28501084
TI  - Barrett Esophagus and Intramucosal Esophageal Adenocarcinoma.
AB  - Barrett esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EAC).
      Developments in imaging and molecular markers, and endoscopic eradication
      therapy, are available to curb the increase of EAC. Endoscopic surveillance is
      recommended, despite lack of data. The cancer risk gets progressively downgraded,
      raising questions about the understanding of risk factors and molecular biology
      involved. Recent data point to at least 2 carcinogenic pathways operating in EAC.
      The use of p53 overexpression and high-risk human papillomavirus may represent
      the best chance to detect progressors. Genome-wide technology may provide
      molecular signatures to aid diagnosis and risk stratification in BE.

PMID- 28501085
TI  - Staging in Esophageal and Gastric Cancers.
AB  - Gastric and esophageal tumors have a poor prognosis; approximately 15% of
      patients are alive at 10 years following diagnosis. Surgical resection plus
      adjunctive chemotherapy or chemoradiotherapy is curative in approximately 50% of
      patients with operable disease, but is also associated with significant
      morbidity. Therefore, accurate preoperative staging is required to spare patients
      unnecessary toxicity and futile surgery. This review evaluates the sensitivity
      and specificities of the modalities used to stage patients with gastroesophageal
      cancer. Staging techniques reviewed include CT, PET, MRI, EUS, and laparoscopy.
      The article concludes with suggestions on appropriate staging tools according to
      site and stage of disease.

PMID- 28501086
TI  - Management of Locally Advanced Gastroesophageal Cancer: Still a Multidisciplinary
      Global Challenge?
AB  - The outcome of patients with locally advanced, resectable gastric cancer, or
      adenocarcinoma of the gastroesophageal junction is poor. In clinical trials,
      multimodality therapy, such as perioperative chemotherapy, preoperative or
      postoperative chemoradiation, or adjuvant chemotherapy led to significant
      increments in survival. Therefore, experts agree that patients with stage II or
      III disease should be offered a multidisciplinary treatment approach. However,
      patients are treated somewhat differently in the different regions of the world
      and survival rates remain far from being satisfactory. Efforts to further improve
      outcome are highly warranted.

PMID- 28501087
TI  - The Role of Radiotherapy in Localized Esophageal and Gastric Cancer.
AB  - Multimodality management has become a core treatment principle for locally
      advanced esophageal, gastroesophageal junction (GEJ), and gastric cancer.
      Radiotherapy serves an important role for optimizing patient outcomes. This
      article reviews the evolving role of radiotherapy in the multidisciplinary
      management of esophageal, GEJ, and gastric cancer, summarizing the results of
      recent clinical trials leading to contemporary accepted treatment approaches. A
      major theme is the evidence supporting the role of radiotherapy in combined
      modality management, particularly the trend toward its delivery in the
      neoadjuvant setting. Also reviewed are novel radiotherapy paradigms and newer
      radiation technologies such as image-guided radiotherapy and MRI-guided
      radiotherapy.

PMID- 28501088
TI  - Management of Metastatic Gastric Cancer.
AB  - Metastatic gastric cancer is an incurable disease. Systemic chemotherapy prolongs
      survival, improves symptom control, and helps maintain a better quality of life
      of patients with metastatic gastric cancer. HER2 testing of the primary tumor
      and/or the metastases is warranted before initiation of first-line treatment.
      This review article outlines the indication and clinical data of medical
      treatment of advanced gastric cancer and highlights aspects of quality of life.

PMID- 28501089
TI  - The Evolving Role of Checkpoint Inhibitors in the Management of Gastroesophageal
      Cancer.
AB  - The connection between inflammation and malignancy has long been recognized in
      gastric and esophageal cancers. Given the considerable success of immune
      checkpoint inhibitors in other tumor types, for example, lung cancer and
      melanoma, much attention is being paid to furthering their role in gastric and
      esophageal cancers. The Cancer Genome Atlas has provided further details of the
      molecular heterogeneity of these tumors, which may help predict responsiveness to
      immune checkpoint inhibitors. This article discusses the rationale for
      investigating these agents in gastroesophageal cancer and summarizes the relevant
      clinical trial data and ongoing studies.

PMID- 28501090
TI  - Antiangiogenic Therapy in Gastroesophageal Cancer.
AB  - Antiangiogenesis therapy is one of only 2 biologically targeted approaches shown
      to improve overall survival over standard of care in advanced adenocarcinoma of
      the stomach or gastroesophageal junction (GEJ). Therapeutic targeting of vascular
      endothelial growth factor receptor 2 improves overall survival in patients with
      previously treated advanced gastric/GEJ adenocarcinoma. No antiangiogenesis
      therapy has demonstrated an overall survival benefit in patients with chemo-naive
      or resectable esophagogastric cancer or in patients whose tumors arise from the
      esophagus. Promising ongoing clinical investigations include the combination of
      antiangiogenesis therapy with immune checkpoint inhibition and anti-human
      epidermal growth factor receptor 2 therapy.

PMID- 28501093
TI  - Future Directions in Improving Outcomes for Patients with Gastric and Esophageal
      Cancer.
AB  - "This issue of Hematology/Oncology Clinics of North America provides an update to
      the current understanding of the physiology of gastric and esophageal cancers and
      the state-of-the-art management of disease. Over the past 10 years, we have
      witnessed dramatic changes in both our understanding of the disease and its
      management. We have 2 new biological agents approved to treat advanced disease,
      with several more prospects under development. In this article, the author looks
      to the future, attempting to answer the question of which advancements will play
      the biggest role in improving patient outcomes in this still-devastating disease.

PMID- 28501092
TI  - Emerging Novel Therapeutic Agents in the Treatment of Patients with
      Gastroesophageal and Gastric Adenocarcinoma.
AB  - With further understanding of the biology of gastric and gastroesophageal
      adenocarcinomas, strides are being made to find effective treatments through
      novel trial designs. This article focuses on the ongoing trials of drugs
      targeting specific hallmarks of gastric and gastroesophageal cancers, including
      oncogene addiction proliferative pathways (fibroblast growth factor receptor 2
      amplified tumors), stem cell inhibition, apoptotic induction through claudin
      inhibitors, and matrix metalloproteinase inhibition. In developing novel
      therapeutics in treatment of patients with gastroesophageal adenocarcinomas,
      parallel research efforts to refine target population and biomarkers are crucial,
      and targeting the tumor genomics and microenvironment may be key in improving
      overall survival.

PMID- 28501091
TI  - Update on Gastroesophageal Adenocarcinoma Targeted Therapies.
AB  - Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality
      worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is
      declining in the United States, proximal esophagogastric junction adenocarcinoma
      (EGJ) incidence is rising. GC and EGJ, together, are treated uniformly in the
      metastatic setting as GEC. Overall survival in the metastatic setting remains
      poor, with few molecular targeted approaches having been successfully
      incorporated into routine care to date-only first-line anti-HER2 therapy for
      ERBB2 amplification and second-line anti-VEGFR2 therapy. This article reviews
      aberrations in epidermal growth factor receptor, MET, and ERBB2, their
      therapeutic implications, and future directions in targeting these pathways.

PMID- 28501094
TI  - The Management of Esophagogastric Cancers Enters a New Era.

PMID- 28501095
TI  - Imaging of IgG4-related disease of the head and neck.
AB  - IgG4-related disease is a systemic, inflammatory disorder typically involving
      multiple organ systems. Several eponymous conditions described previously in the
      clinical and radiology literature are now recognised to be part of the IgG4
      related disease spectrum. This includes multiple manifestations in the head and
      neck region, which are the subject of this review. Imaging can occasionally
      suggest the specific diagnosis of IgG4 disease. More commonly, it will be
      included in a limited differential diagnosis that requires clarification with the
      aid of image-guided biopsy. There are strict histopathological criteria for the
      diagnosis of IgG4-related disease.

PMID- 28501096
TI  - Combined diffusion-weighted imaging and dynamic contrast-enhanced MRI for
      differentiating radiologically indeterminate malignant from benign orbital
      masses.
AB  - AIM: To evaluate the performance of the combination of diffusion-weighted (DW)
      and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for
      differentiating radiologically indeterminate malignant from benign orbital
      masses. MATERIALS AND METHODS: Sixty-five patients with orbital masses (36 benign
      and 29 malignant) underwent DW and DCE MRI examinations for pre-treatment
      evaluation. The apparent diffusion coefficient (ADC) was derived from DW imaging
      data using the mono-exponential model. The volume transfer constant (Ktrans), the
      flux rate constant between the extravascular extracellular space and the plasma
      (Kep), and the extravascular extracellular volume fraction (Ve) were calculated
      using modified Tofts model. Differences in quantitative metrics were tested using
      independent-samples t test. Receiver operating characteristic (ROC) curve
      analyses were used to determine and compare the diagnostic ability of each
      significant metric. RESULTS: The malignant group demonstrated significantly lower
      ADC (0.711+/-0.260 versus 1.187+/-0.389, p<0.001) and higher Kep values (1.265+/
      0.637 versus 0.871+/-0.610, p=0.008) than the benign group. Optimal diagnostic
      performance (area under the ROC curve [AUC], 0.941; sensitivity, 0.966;
      specificity, 0.917) could be achieved using combined ADC and Kep values as the
      diagnostic index. The diagnostic performance of the combination of ADC and Kep
      was significantly better than Kep alone (p=0.006). Compared with ADC alone,
      combined ADC and Kep values also showed higher AUC (0.941 versus 0.898), although
      the difference did not reach statistical significance (p=0.220). CONCLUSION: Kep
      and ADC could help to differentiate radiologically indeterminate malignant from
      benign orbital masses. The combination of DW and DCE MRI might improve the
      differentiating performance.

PMID- 28501097
TI  - Orofacial pain and headaches associated with exfoliation glaucoma.
AB  - BACKGROUND AND OVERVIEW: Exfoliation syndrome is the most common identifiable
      cause of open-angle glaucoma. The authors report a case of exfoliation glaucoma
      in a patient who had orofacial pain. CASE DESCRIPTION: A 77-year-old woman was
      treated at the orofacial pain clinic for left-sided facial pain and headaches of
      7 months' duration. Her cataracts and open-angle glaucoma had been diagnosed
      approximately 3 years earlier. Her main symptoms were orofacial pain, eye
      redness, inflammation of the eyelids, and eyelid edema. Magnetic resonance
      imaging showed no evidence of intracranial or extracranial pathology. Hemicrania
      continua was considered as a possible diagnosis. Indomethacin was prescribed but
      did not affect her headaches. She then went to an ophthalmologist to rule out
      secondary headaches. Intraocular pressure was 13 millimeters of mercury in the
      right eye and 67 mm Hg in the left eye. The ophthalmologist made a diagnosis of
      exfoliation glaucoma, and the patient underwent surgical treatment for the
      glaucoma and cataracts. After surgery, she was free of symptoms, and intraocular
      pressure was 15 mm Hg in the left eye. CONCLUSIONS AND PRACTICAL IMPLICATIONS:
      During differential diagnosis, dentists need to consider intraoral and systemic
      conditions that can mimic odontogenic or orofacial pain disorders in the
      patient's medical history and that have a higher incidence associated with the
      patient's age.

PMID- 28501098
TI  - Alterations in intestinal microbiota relate to intestinal failure-associated
      liver disease and central line infections.
AB  - BACKGROUND: The gut microbiota plays a vital role in modulating the metabolic and
      immune functions of the intestines. We aimed to analyze the dysbiosis of
      microbiota in infants with short bowel syndrome (SBS) with different
      complications. PROCEDURE: We included 26 fecal samples from 18 infants with SBS
      during parenteral nutrition. The samples were categorized into three groups:
      asymptomatic, parenteral nutrition-associated liver disease (PNALD), and central
      line-associated bloodstream infection (CLABSI). Seven healthy infants were
      enrolled as controls. Fecal microbiota, secretory IgA, calprotectin, bile acids,
      and short chain fatty acids were detected. RESULTS: The bacterial diversity of
      the Asymptomatic and Control Groups was significantly higher than that in the
      PNALD and CLABSI Groups. Proteobacteria was the most pronounced phylum in the
      PNALD and CLABSI Groups. Decreased acetate was observed in all SBS samples;
      however, fecal secretory IgA and calprotectin and the proportion of primary and
      secondary bile acids did not differ from those in healthy controls. CONCLUSIONS:
      Marked alterations of the intestinal microbiota with decreased level of acetate
      were shown in SBS patients compared with healthy controls. Over-abundance of
      Proteobacteria (especially Enterobacteriaceae) was found in the samples from the
      PNALD and CLABSI Groups. LEVEL OF EVIDENCE: Prognosis Study, Level I.

PMID- 28501099
TI  - Entropy of aqueous surfaces. Application to polymeric Langmuir films.
AB  - Measuring surface (excess) entropies provides a bounty of valuable structural
      information that is hard to obtain otherwise. In the paper these quantities are
      defined and procedures of measurements discussed. Mostly they involve
      measurements at different temperatures. A review is given for interfaces with
      aqueous solutions in the absence of polymers. This review illustrates how,
      sometimes unanticipated, pieces of information are obtained, for example with
      cloud seeding and a possible explanation of the Jones-Ray effect. As a novel
      extension the procedure is applied to deposited, or Langmuir, monolayers of
      poly(ethylene oxide)-poly(propylene oxide) block copolymers. It will be shown how
      the various phase transitions and associated configurations of these polymers can
      be recognized and monitored.

PMID- 28501100
TI  - Comparison of Direct Current Synchronized Cardioversion to Ibutilide-Guided
      Catheter Ablation for Long-Term Sinus Rhythm Maintenance After Isolated Pulmonary
      Vein Isolation of Persistent Atrial Fibrillation.
AB  - Use of the antiarrhythmic ibutilide after isolated pulmonary vein isolation (PVI)
      might distinguish atrial remodeling severity and cases requiring further
      substrate modification, thereby improving efficacy of persistent atrial
      fibrillation (AF) treatment. Ninety-six consecutive patients with persistent AF
      were randomized after PVI to either direct current synchronized cardioversion
      (DCC group, n = 48) or 1 mg of intravenous ibutilide (ibutilide group, n = 48)
      followed by no further intervention if AF converted to sinus rhythm (SR) within
      30 minutes (ibutilide conversion subgroup) or by complex fractionated atrial
      electrogram (CFAE) ablation until SR recovery or complete CFAE elimination
      (ibutilide nonconversion subgroup). With similarly distributed baseline
      characteristics and no serious postablation complications, the primary end point
      of 12-month SR maintenance rate after PVI was significantly higher for ibutilide
      versus the DCC group before (75% vs 56%; p = 0.042) or after (83% vs 60%; p =
      0.011) reablation at physician's discretion for recurrence beyond 3 months after
      PVI. After ibutilide administration, 21 of 48 patients (44%) converted to SR at
      17 +/- 8 minutes (mean +/- SD); those in the ibutilide nonconversion subgroup had
      larger atrial size (47 +/- 4 vs 45 +/- 4; p = 0.025) and CFAE area (29 +/- 8 vs
      12 +/- 5; p = 0.001) and longer AF duration (27 +/- 6 vs 21 +/- 10; p = 0.026).
      Among ibutilide conversion and nonconversion subgroups and DCC group, procedure,
      ablation, and x-ray exposure times differed significantly, as did 12-month SR
      maintenance rate before (81% vs 70% vs 56%; p = 0.043) or after reablation (86%
      vs 81% vs 60%; p = 0.042). In conclusion, in persistent AF treatment, ibutilide
      guided ablation after PVI yields higher 1-year SR maintenance rate than PVI only.

PMID- 28501101
TI  - Risk assessment: A hindrance or a help to landfill management?

PMID- 28501102
TI  - Integration of biological effects, fish histopathology and contaminant
      measurements for the assessment of fish health: A pilot application in Irish
      marine waters.
AB  - This study investigates the use of a weight of evidence (WOE) approach to
      evaluate fish health status and biological effects (BEs) of contaminants for
      assessment of ecosystem health and discusses its potential application in support
      of the Marine Strategy Framework Directive (MSFD). External fish disease, liver
      histopathology and several BEs of contaminant exposure including 7-ethoxy
      resorufin O-de-ethylase (EROD), acetylcholinesterase (AChE), bile metabolites,
      vitellogenin (VTG) and alkali labile phosphates (ALP) were measured in two
      flatfish species from four locations in Ireland. Contaminant levels in fish were
      generally low with PCBs in fish liver below OSPAR environmental assessment
      criteria (EAC). There were consistencies with low PCB levels, EROD and PAH bile
      metabolite levels detected in fish. Dab from Cork, Dublin and Shannon had the
      highest relative prevalence of liver lesions associated with the carcinogenic
      pathway. An integrated biomarker response (IBR) showed promise to be useful for
      evaluation of environmental risk, although more contaminant parameters in liver
      are required for a full assessment with the present study.

PMID- 28501103
TI  - mRNA decay is regulated via sequestration of the conserved 5'-3' exoribonuclease
      Xrn1 at eisosome in yeast.
AB  - We describe a novel mechanism of mRNA decay regulation, which takes place under
      the conditions of glucose deprivation in the yeast Saccharomyces cerevisiae. The
      regulation is based on temporally stable sequestration of the main 5'-3' mRNA
      exoribonuclease Xrn1 at the eisosome, a plasma membrane-associated protein
      complex organizing a specialized membrane microdomain. As documented by
      monitoring the decay of a specific mRNA substrate in time, Xrn1-mediated mRNA
      degradation ceases during the accumulation of Xrn1 at eisosome, but the eisosome
      associated Xrn1 retains its functionality and can be re-activated when released
      to cytoplasm following the addition of glucose. In cells lacking the eisosome
      organizer Pil1, Xrn1 does not associate with the plasma membrane and its activity
      is preserved till the stationary phase. Thus, properly assembled eisosome is
      necessary for this kind of Xrn1 regulation, which occurs in a liquid culture as
      well as in a differentiated colony.

PMID- 28501104
TI  - Knockdown of Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy
      terminal domain 2 inhibits cell division and increases apoptosis in gastric
      cancer.
AB  - BACKGROUND: Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy
      terminal domain 2 (CITED2) is a pleiotropic protein associated with numerous cell
      functions, including transcription and differentiation. The role of CITED2 has
      been investigated in a number of malignancies; however, the roles of this protein
      in gastric cancers remain unclear. Therefore, we determined the role of CITED2 in
      gastric cancers. MATERIALS AND METHODS: Gastric cancer cell lines (MKN74, MKN28,
      7901, and AGS) were used to assess CITED2 transcript levels. Messenger RNA levels
      were determined using quantitative polymerase chain reaction. Lentiviral vectors
      containing CITED2 small interfering RNA were used to knockdown CITED2 expression.
      Cell proliferation was assessed with fluorescent imaging and 3-(4,5
      dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assays. Apoptosis and cell
      cycle stages were assessed through flow cytometry, and formation of colonies was
      determined using a fluorescent microscope. RESULTS: All cell lines tested in this
      study expressed CITED2. The cell line expressing the highest levels of CITED2
      (MKN74) showed significant knockdown of endogenous CITED2 expression on
      lentiviral infection. Cell proliferation was shown to be lower in CITED2
      knockdown MKN74 cells. G1/S-phase cell cycle arrest was observed on silencing of
      CITED2 in MKN74 cells. A significant increase in apoptosis was observed on CITED2
      knock down in MKN74 cells, while colony forming ability was significantly
      inhibited after knock down of CITED2. CONCLUSIONS: CITED2 supports gastric cancer
      cell colony formation and proliferation while inhibiting apoptosis making it a
      potential gene therapy target for gastric cancer.

PMID- 28501105
TI  - Surviving rectal cancer: examination of racial disparities surrounding access to
      care.
AB  - BACKGROUND: The aim of this study was to evaluate whether survival differences
      are attributable to disproportionate access to stage-specific rectal cancer
      treatment recommended by the National Comprehensive Care Network. METHODS: A
      retrospective analysis of the National Cancer Data Base between 1998 and 2006 was
      performed. A series of Kaplan-Meier survival analyses were used to compare 5-y
      survival among race cohorts. Propensity score matching was used to compare
      Caucasian and African American patients who received the same treatment by
      accounting for covariates. RESULTS: 5-y overall survival in African Americans was
      50.7% versus 56.2% in Caucasians (P < 0.001). In patients with stage I-III
      disease, 5-y survival was 58.7% in African Americans versus 63.1% in Caucasians
      (P < 0.001). Analysis of patients receiving surgery for stage I-III disease,
      revealed a 61.1% 5-y survival in African Americans versus 65.8% in Caucasians (P
      < 0.001). Propensity score matching did not eliminate the racial disparity. The
      median survival for Caucasian patients was 109.6 mo as compared to 85.8 mo for
      African Americans (P < 0.001). CONCLUSIONS: These data show that access to
      standard care appears to decrease but not eliminate the survival differences
      between African Americans and Caucasians with rectal cancer.

PMID- 28501106
TI  - Concurrent endocrine and other surgical procedures: an institutional experience.
AB  - INRODUCTION: The number of endocrine procedures, specifically parathyroidectomy,
      thyroidectomy, and adrenalectomy, being performed is increasing. There is a
      paucity of literature on the feasibility of combining these procedures with other
      surgical procedures. Therefore, the aim of this study was to determine the effect
      of performing concurrent surgical procedures on postoperative outcomes. METHODS:
      This is a single institution retrospective review of multiple prospectively
      maintained databases of patients who underwent elective thyroidectomy,
      parathyroidectomy, and/or adrenalectomy in combination with another procedure.
      The other procedures included soft tissue, breast or hernia, abdominal major,
      abdominal minor, cervical, and "other". Demographics, operative details, length
      of-stay, and 30-d outcomes were reviewed. "Endocrine-specific" complications
      included recurrent laryngeal nerve injury, hypoparathyroidism, cervical wound
      infection, hematoma, and other. RESULTS: The cohort comprised 104 patients.
      Overall, 19 (18%) patients had 21 complications, including endocrine-specific
      complications in eleven (11%) patients. These eleven complications included
      recurrent laryngeal nerve injury (n = 3; 3%), hematoma (n = 2; 2%), wound
      infection (n = 1; 1%), transient hypoparathyroidism (n = 2; 2%), and other (n =
      3; 3%). The remaining complications included three (3%) general complications,
      six (6%) patients with complications related to the concurrent procedure, and one
      patient who underwent an open adrenalectomy and hysterectomy and developed a
      midline wound dehiscence, which could not be specifically attributed to either
      procedure. CONCLUSIONS: Less than 5% of patients undergoing a surgical endocrine
      procedure underwent a concurrent procedure, ranging from soft tissue to major
      abdominal. Short-term endocrine-specific complications were managed safely,
      suggesting that concurrent procedures can be considered, with minimal effect on
      patient outcomes.

PMID- 28501107
TI  - Melatonin reduces changes to small intestinal microvasculature during systemic
      inflammation.
AB  - BACKGROUND: Systemic inflammation is known to impair the microcirculation in
      intestine and other organs as a result of multifactorial events. Here, we show
      that melatonin selectively reduces changes to the small intestinal
      microvasculature during systemic inflammation. MATERIALS AND METHODS:
      Lipopolysaccharide (LPS) was infused at a rate of 0.5 mg/kg * h to induce
      systemic inflammation in male Wistar rats. Melatonin (single dose: 3 mg/kg * 15
      min) was intravenously administered before as well as 120 and 240 min after the
      beginning of the LPS infusion. Systemic parameters were determined in regular
      intervals. Small intestine, liver, and kidney were histologically (structure of
      the microvessels, intravascular blood accumulation, and hemorrhages) and
      immunohistochemically (mast cells, granulocytes, and macrophages) analyzed.
      RESULTS: Continuous infusion of LPS resulted in dilated microvessels with
      intravascular blood accumulation (congestion) in liver and small intestine, the
      latter being particularly pronounced. Blood vessel walls remained intact, there
      were no hemorrhages. Melatonin significantly reduced these changes to the
      microvasculature in small intestine, but not in liver. It further reduced mast
      cell and granulocytes count in small intestine enhanced by LPS. However, except
      for the systemic blood pressure, melatonin neither improved LPS-dependent changes
      to systemic parameters nor mortality. CONCLUSIONS: Changes to the
      microvasculature during systemic inflammation are most pronounced in small
      intestine. Melatonin selectively diminishes these changes to small intestinal
      microvasculature, probably by reducing the local immune cells recruitment.
      However, changes to the small intestine are not decisive for the survival. We
      assume that the therapeutic benefit of melatonin is more likely in local
      intestinal inflammation.

PMID- 28501108
TI  - Vendor effects on murine gut microbiota influence experimental abdominal sepsis.
AB  - BACKGROUND: Experimental animal models are indispensable components of
      preclinical sepsis research. Reproducible results highly rely on defined and
      invariant baseline conditions. Our hypothesis was that the murine gut microbiota
      varies among different distributors of laboratory animals and that these
      variations influence the phenotype of abdominal sepsis derived from a bacterial
      inoculum model (intraperitoneal stool injection). MATERIALS AND METHODS: Male
      C57BL/6 mice (8-wk old) purchased from Charles River (CR), Janvier (J), and
      Harlan (H) were sacrificed, and the bacterial composition of feces was analyzed
      using CHROMagar orientation medium. Stool was injected intraperitoneally into CR
      mice, followed by clinical observation and gene expression analysis. Experiments
      were repeated 16 mo later under the same conditions. RESULTS: Stool analysis
      revealed profound intervendor differences in bacterial composition, mainly
      regarding Staphylococcus aureus and Bacillus licheniformis. Mice challenged with
      CR as well as H feces developed significantly higher severity of disease and died
      within the observation period, whereas stool from J mice did not induce any of
      these symptoms. Real-time polymerase chain reaction revealed corresponding
      results with significant upregulation of proinflammatory cytokines and vascular
      leakage-related mediators in CR and H injected animals. Sixteen months later, the
      bacterial fecal composition had significantly shifted. The differences in
      clinical phenotype of sepsis after intraperitoneal stool injection had vanished.
      CONCLUSIONS: We are the first to demonstrate vendor and time effects on the
      murine fecal microbiota influencing sepsis models of intraabdominal stool
      contamination. The intestinal microbiota must be defined and standardized when
      designing and interpreting past and future studies using murine abdominal sepsis
      models.

PMID- 28501109
TI  - Sarcopenia: a new predictor of postoperative complications for elderly gastric
      cancer patients who underwent radical gastrectomy.
AB  - BACKGROUND: A geriatric assessment is needed to identify high-risk elderly
      patients with gastric cancer. However, the current geriatric assessment has been
      considered to be either time-consuming or subjective. The present study aimed to
      investigate the predictive effect of sarcopenia on the postoperative
      complications for elderly patients who underwent radical gastrectomy. MATERIALS
      AND METHODS: We conducted a prospective study of patients who underwent radical
      gastrectomy from August 2014 to December 2015. Computed tomography-assessed
      lumbar skeletal muscle, handgrip strength, and gait speed were measured to define
      sarcopenia. RESULTS: Sarcopenia was present in 69 of 240 patients (28.8%) and was
      associated with lower body mass index, lower serum albumin, lower hemoglobin, and
      higher nutritional risk screening 2002 scores. Postoperative complications
      significantly increased in the sarcopenic patients (49.3% versus 24.6%, P <
      0.001), compared with nonsarcopenic patients. The multivariate analysis
      demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P < 0.001)
      and the Charlson comorbidity index >=2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P
      = 0.027) were independent risk factors for postoperative complications.
      CONCLUSIONS: Sarcopenia, presented as a new geriatric assessment factor, was a
      strong and independent risk factor for postoperative complications of elderly
      patients with gastric cancer.

PMID- 28501110
TI  - Arachidonic acid causes hidden blood loss-like red blood cell damage through
      oxidative stress reactions.
AB  - BACKGROUND: Hidden blood loss (HBL) often occurs in the prosthetic replacement
      for joint, but the mechanism is still not clear. MATERIALS AND METHODS: This
      study tried to establish an animal model of HBL by injecting arachidonic acid
      (AA) into the Sprague-Dawley rats. Different concentrations of AA were injected
      into the tail veins of the rats, and blood samples were collected before and
      after administration at 24, 48, and 72 h. A complete blood count was obtained by
      to find the hemoglobin (Hb) and red blood cell (RBC) count changes. The
      glutathione peroxidase (GSH-PX) and total superoxide dismutase (T-SOD) activities
      and hydrogen peroxide (H2O2) levels were detected. The morphological changes of
      erythrocyte were observed under a polarizing microscope. The absorbance values of
      the blood samples were tested to determine the presence of ferryl Hb. RESULTS:
      HBL occurred in the experimental groups when the concentration of AA reached 10
      mmol/L; Hb and RBC values decreased sharply at 24- and 48-h postinjection. This
      was followed by reduced activities of GSH-PX and T-SOD and decreased levels of
      H2O2. Moreover, the pathologic changes of red cell morphology mainly presented as
      pleomorphic RBC morphology, including cell rupture. The absorbance values of the
      blood samples were in accordance with ferryl Hb features. RBC and Hb values were
      relatively stable at 72 h. The GSH-PX and T-SOD activities and H2O2 levels
      gradually increased up to a balanced state. CONCLUSIONS: The study concluded that
      high concentrations of AA can induce oxidative stress reactions in the body,
      causing acute injury of RBCs, which is closely related to HBL.

PMID- 28501111
TI  - Laparoscopic dissection and division of distal fistula in boys with rectourethral
      fistula.
AB  - BACKGROUND: Congenital rectourethral fistula (RUF) is the most common form of
      anorectal malformations found in boys. The aim of this study is to review our
      experience with dissection and division of distal fistula using laparoscopic
      surgery in the management of RUF, especially rectourethral bulbar fistula.
      METHODS: One hundred and two consecutive boys with congenital RUF who underwent
      conventional or single-incision laparoscopic surgery between July 2008 and June
      2015 were enrolled in the study. The dissection of the distal fistula was
      performed along submucosal layer to a level 0.5 cm proximal to the urethra.
      Rectal mucosa of the fistula was dissected to the distal most point and
      completely transected flush with the posterior urethra. The residual muscular
      cuff was ligated with Hem-o-Lock clip or 5-0 PDS suture. Voiding
      cystourethrography and pelvic magnetic resonance imaging were performed at 3 mo,
      6 mo, and 1 y postoperatively. RESULTS: All patients successfully underwent
      laparoscopic surgery without conversion. The mean age at the time of operation
      was 4.3 +/- 2.9 mo. The operative times for the rectoprostatic fistula and
      rectobulbar fistula were similar (118.2 versus 119.4 min, P = 0.082). There was
      no significant difference in average operative time between conventional
      laparoscopic surgery group and single-incision laparoscopic surgery group (118.8
      versus 119.1 min, P = 0.281). There was no injury to the urethra or vas deferens.
      The urethral catheter was removed on postoperative day 10. All patients were
      followed up. The median follow-up period was 3.3 +/- 1.8 y. No recurrent fistula
      or urethral diverticulum was detected on voiding cystourethrography and pelvic
      MRI at 1 y. CONCLUSIONS: Submucosal dissection and division of distal fistula
      using a laparoscopic approach is safe, feasible, and effective for congenital
      RUF, especially bulbar fistula, in boys.

PMID- 28501112
TI  - Early results of a surgeon-led, perioperative surgical home.
AB  - BACKGROUND: The Perioperative Surgical Home is a novel care model designed to
      provide patient-centered, high-quality surgical care. In 2013, we implemented
      POSH, a pilot Peri-Operative Surgical Home at Phoenix Indian Medical Center
      (PIMC), an Indian Health Service hospital, as a quality improvement project.
      After 2 y, we sought to quantify the impact of POSH on the quality of surgical
      care at PIMC. MATERIALS AND METHODS: We conducted a retrospective review of 33
      surgical patients who underwent surgery at PIMC through the POSH process between
      2013 and 2015 matched to 64 historical controls with similar operations. Study
      patients underwent surgery via the POSH treatment process. Primary outcomes were
      composite measures of (1) care standards and (2) care goals. Success was defined
      as meeting seven of nine care standards and six of eight care goals. RESULTS AND
      DISCUSSION: The mean number of care standards met was 8.1 +/- 1.0 versus 4.2 +/-
      1.4 (P < 0.001) and the mean number of care goals met was 6.7 +/- 0.8 versus 6.1
      +/- 1.1 (P = 0.005) for POSH patients and historical controls, respectively.
      Patients participating in the POSH model were 8.6 (95% confidence interval: 3.5
      22.3) and 1.5 (95% confidence interval: 1.2-1.9) times more likely to meet the
      minimum number of care standards and goals, respectively. Fourteen of the study
      patients (42%) would not have been offered surgery at PIMC before POSH due to
      elevated surgical risk. CONCLUSIONS: POSH may have improved quality of surgical
      care at PIMC while expanding services to more complex patients. POSH may present
      an opportunity for improved surgical quality in resource-constrained
      environments.

PMID- 28501113
TI  - Clinical Acuity Shorthand System: a standardized classification tool to
      facilitate handoffs.
AB  - BACKGROUND: The handoff of medical information from one provider to another can
      be inefficient and error prone, potentially undermining patient safety. Although
      several tools for structuring handoffs exist, none provide a brief, standardized
      framework for ensuring that patient acuity is efficiently and reliably
      communicated. We aim to introduce and perform initial testing of the Clinical
      Acuity Shorthand System (CLASS) (Copyright 2015, Duke University. All rights
      reserved.) for surgery, a patient classification tool intended to facilitate
      efficient communication of key patient information during handoffs. MATERIALS AND
      METHODS: Surgical trainees at a single center were asked to perform an exercise
      involving application of CLASS to 10 theoretical patient scenarios and to then
      complete a brief survey. Responses were scored based on similarity to target
      answers. Performance was evaluated overall and between groups of trainees. Time
      required to complete the exercise was also determined and perceived utility of
      the system was assessed based on survey responses. RESULTS: The study task was
      completed by 17 participants. Mean time to task completion was 10.3 +/- 8.4 min.
      Accuracy was not decreased, and was in fact superior, in junior trainees. Most
      respondents indicated that such a system would be feasible and could prevent
      medical errors. CONCLUSIONS: CLASS is a novel system that can be learned quickly
      and implemented readily by trainees and can be used to convey patient information
      concisely and with acceptable fidelity regardless of level of training. Further
      study examining application of this system on clinical surgical services is
      warranted.

PMID- 28501114
TI  - Evaluation of palliative care training and skills retention by medical students.
AB  - BACKGROUND: Training in palliative and end-of-life care has been introduced in
      medical education; however, the impact of such training and the retention of
      skills and knowledge have not been studied in detail. This survey study examines
      long-term follow-up on end-of-life communication skills training, evaluation, and
      skills retention in medical students. MATERIALS AND METHODS: During the surgical
      clerkship, all third-year medical students received communication skills training
      in palliative care using simulated patients. The training involved three
      scenarios involving diverse surgical patients with conditions commonly
      encountered during the surgical clerkship. The students used web-based best
      practice guidelines to prepare for the patient encounters. The following
      communication abilities were evaluated: (1) giving bad news clearly and with
      empathy, (2) initiating death and dying conversations with patients and/or their
      family members, (3) discussing do not resuscitate status and exploring
      preferences for end-of-life care, and (4) initiating conversations regarding
      religious or spiritual values and practices. All students were surveyed after 1
      year (12-24 mo) to ascertain: (1) the retention of skills and/or knowledge gained
      during this training, (2) application of these skills during subsequent clinical
      rotations, and (3) overall perception of the value added by the training to their
      undergraduate medical education. These results were correlated with residency
      specialty choice. RESULTS: The survey was sent to all graduating fourth-year
      medical students (n = 105) in our program, of which 69 students responded to the
      survey (66% response rate). All respondents agreed that palliative care training
      is essential in medical school training. Seventy percent of the respondents
      agreed that the simulated encounters allowed development of crucial conversation
      skills needed for palliative/end-of-life care communications. The most useful
      part of the training was the deliberate practice of "giving bad news" (85%). Most
      of the respondents (80%) indicated retention of overall communication skills with
      regard to approach and useful phrases. Forty-five percent claimed retention of
      communication skills surrounding death and dying, and 44% claimed retention of
      end-of-life preferences/advance directives/do not resuscitate. Relatively few
      respondents (16%) retained skills regarding religious or spiritual values. There
      was no correlation between training evaluation/skill retention and the area of
      residency specialty the students pursued on graduation. CONCLUSIONS: Early
      training in palliative and end-of-life care communication is feasible and
      effective during the surgical clerkship. Students highly valued the simulated
      patient and/or family discussions and retained most of the skills and knowledge
      from the experiential simulated encounters. However, students felt the skills
      developed could be reinforced with opportunities to observe their attending
      physicians or residents leading such discussions and involving students in such
      discussions as and when appropriate.

PMID- 28501115
TI  - Postconditioning attenuates coronary perivascular and interstitial fibrosis
      through modulating angiotensin II receptors and angiotensin-converting enzyme 2
      after myocardial infarction.
AB  - BACKGROUND: Postconditioning (Postcon) is known to reduce infarct size. This
      study tested the hypothesis that Postcon attenuates the perivascular and
      interstitial fibrosis after myocardial infarction through modulating angiotensin
      II-activated fibrotic cascade. MATERIALS AND METHODS: Male Sprague-Dawley rats
      were subjected to 45-min coronary occlusion followed by 1 and 6 wk of
      reperfusion. Postcon was applied at the onset of reperfusion with four cycles of
      10/10-s reperfusion-ischemia at the onset of reperfusion. Preconditioning
      (Precon) with two cycles of 5/5-min ischemia-reperfusion was applied before
      coronary occlusion. RESULTS: Postcon reduced angiotensin-converting enzyme
      protein and expression in the perivascular area and intermyocardium, coincident
      with the less-expressed angiotensin II receptor, type 1, enhanced angiotensin II
      receptor, type 2, and angiotensin converting enzyme 2. Postcon lowered the
      monocyte chemoattractant protein-1 and inhibited the populations of interstitial
      macrophages (60 +/- 12 versus 84 +/- 9.5 number per high-powered field [HPF] in
      control, P < 0.05). Along with these modulations, Postcon also downregulated
      transforming growth factor beta1 protein and inhibited proliferation of alpha
      smooth muscle actin expressing myofibroblasts (41 +/- 11 versus 79 +/- 8.2 number
      per HPF in control, P < 0.05), consistent with downregulated phospho-Smad2 and
      phospho-Smad3. Furthermore, the synthesis of collagen I and III was attenuated,
      and the perivascular-interstitial fibrosis was inhibited by Postcon as
      demonstrated by reduced perivascular fibrosis ratio (0.6 +/- 0.6 versus 1.6 +/-
      0.5 per HPF in control, P < 0.05) and smaller collagen-rich area (16 +/- 4.7
      versus 34 +/- 9.2% per HPF in control, P < 0.05). Precon conferred a comparable
      level of protection as Postcon did in all parameters measured, suggesting
      protection trigged by this endogenous stimulation can be achieved when it was
      applied either before ischemia or after reperfusion. CONCLUSIONS: These results
      suggest that Postcon could be selected as an adjunctive intervention with other
      existing therapeutic drugs to treat the fibrosis-derived heart failure patients
      after myocardial infarction.

PMID- 28501116
TI  - Usefulness of virtual reality in assessment of medical student laparoscopic
      skill.
AB  - BACKGROUND: This study evaluates if undergraduate medical trainees' laparoscopic
      skills acquisition could be assessed using a virtual reality (VR) simulator and
      how the resultant metrics correlate with performance of Fundamentals of
      Laparoscopic Surgery (FLS) tasks. Our hypothesis is that the VR simulator metrics
      will correlate with passing results in a competency-based curriculum (FLS).
      MATERIALS AND METHODS: Twenty-eight fourth-year medical students applying for
      surgical residency were recruited to participate in a VR training curriculum
      comprised of camera navigation, hand eye coordination, and FLS tasks: circle
      cutting (CC), ligating loop (LL), peg transfer (PT), and intracorporeal knot
      tying (IKT). Students were given 8 wk to achieve proficiency goals, after which
      they were observed performing FLS tasks. The ability of the VR simulator to
      detect penalties in each of the FLS tasks and correlations of time taken to
      complete tasks are reported. RESULTS: Twenty-five students trained in all
      components of the curriculum. All students were proficient in camera navigation
      and hand eye coordination tasks. Proficiency was achieved in CC, LL, PT, and IKT
      by 21, 19, 23, and one student, respectively. VR simulation showed high
      specificity for predicting zero penalties on the observed CC, LL, and PT tasks
      (80%, 75%, and 80%, respectively). CONCLUSIONS: VR can be used to assess medical
      student's acquisition of laparoscopic skills. The absence of penalties in the
      simulator reasonably predicts the absence of penalties in all FLS skills, except
      IKT. The skills acquired by trainees can be used in residency for further
      monitoring of progress toward proficiency.

PMID- 28501117
TI  - Institutional variation in surgical care for early-stage breast cancer at
      community hospitals.
AB  - BACKGROUND: There is significant institutional variation in the surgical care of
      breast cancer, and this may reflect access to services and resultant physician
      practice patterns. In previous studies, specialty care has been associated with
      variation in the operative treatment of breast cancer but has not been evaluated
      in a community setting. This study investigates these issues in a cohort of 59
      community hospitals in the United States. MATERIALS AND METHODS: Data on patients
      receiving an operation for breast cancer (2006-2009) in a large, geographically
      diverse cohort of hospitals were obtained. Administrative data, autoabstracted
      cancer-specific variables from free text, and multiple other data sets were
      combined. Polymotous logistic regression with multilevel outcomes identified
      associations between these variables and surgical treatment. RESULTS: At 59
      community hospitals, 4766 patients underwent breast conserving surgery (BCS),
      mastectomy, or mastectomy with reconstruction. The older patients were most
      likely to receive mastectomy alone, whereas the younger age group underwent more
      reconstruction (age <50), and BCS was most likely in patients aged 50-65.
      Surgical procedure also varied according to tumor characteristics. BCS was more
      likely at smaller hospitals, those with ambulatory surgery centers, and those
      located in nonmetropolitan areas. The likelihood of reconstruction doubled when
      there were more reconstructive surgeons in the health services area (P = 0.02).
      BCS was more likely when radiation oncology services were available within the
      hospital or network (P = 0.04). CONCLUSIONS: Interpretation of these results for
      practice redesign is not straightforward. Although access to specialty care is
      statistically associated with type of breast surgical procedure, clinical impact
      is limited. It may be more effective to target other aspects of care to ensure
      each patient receives treatment consistent with her individual preferences.

PMID- 28501118
TI  - Impact of chromogranin A, differentiation, and mitoses in nonfunctional
      pancreatic neuroendocrine tumors <= 2 cm.
AB  - BACKGROUND: Small pancreatic neuroendocrine tumors (PNETs) are a unique subset of
      pancreatic neoplasms. Chromogranin A (CgA) levels, mitotic rate, and histologic
      differentiation are often used to characterize PNET behavior. This study
      evaluates the impact of these factors on survival in patients with PNETs.
      METHODS: The US National Cancer Data Base (1998-2012) was reviewed for patients
      with stages I-III, nonfunctional PNETs <=2 cm. Clinicopathologic characteristics
      were collected, and univariate and multivariate survival analyses were performed.
      RESULTS: Of 1159 patients, 872 had tumor differentiation recorded, 403 had
      mitotic rate, and 217 patients had CgA. Mitotic rate >20 mitoses per 10 high
      power microscopic fields was significantly associated with survival (hazard ratio
      [HR] = 10.6, P = 0.002) in multivariate analysis. Of those who underwent
      resection, there was no significant difference in positive lymph nodes between
      high (>100 ng/mL) and low (<=100 ng/mL) CgA levels (0.27 versus 0.37, P =
      0.4440). Multivariate analyses of patients with both grade and CgA recorded found
      poorly differentiated tumors and very high CgA (>400 ng/mL) negatively impacted
      survival (HR = 2.99, P < 0.0001, HR = 3.47, P < 0.0001, respectively). Propensity
      score matching demonstrated improved 5-y survival in patients who underwent
      surgical resection, P < 0.0001. CONCLUSIONS: Poorly differentiated disease should
      be considered an indicator of worse prognosis in nonfunctional PNETs <=2 cm.
      Surgical resection appears to improve survival in these patients.

PMID- 28501119
TI  - Nonocclusive mesenteric infarction after cardiac surgery: potential biomarkers.
AB  - BACKGROUND: Nonocclusive mesenteric ischemia can cause intestinal infarction but
      the diagnosis is challenging. This prospective study evaluated three plasma
      biomarkers of intestinal infarction after cardiac surgery. MATERIALS AND METHODS:
      Patients were recruited after cardiac surgery if they required laparotomy (with
      or without intestinal resection) for suspected nonocclusive mesenteric ischemia.
      Plasma levels of D-lactate, intestinal fatty acid-binding protein (i-FABP), and
      smooth muscle actin (SMA) before laparotomy were measured. RESULTS: Twenty
      patients were recruited (68 +/- 9 y, EuroSCORE: 8.7 +/- 2.8, mortality 70%). A
      positive laparotomy (n = 13) was associated with no change in D-lactate (P =
      0.95), decreased i-FABP (P = 0.007), and increased SMA (P = 0.01). All patients
      with high SMA had a positive laparotomy. A subgroup analysis was undertaken in
      the eight patients who required multiple laparotomies. D-lactate increased
      between the two laparotomies in nonsurvivors (n = 4). Plasma i-FABP (P = 0.008)
      and SMA (P = 0.036) significantly decreased after the bowel resection, regardless
      of survival outcome. CONCLUSIONS: None of the biomarkers were accurate enough to
      reliably diagnose intestinal infarction. However, all patients with high values
      of SMA developed intestinal infarction, thus warranting further investigation. An
      increasing D-lactate after intestinal resection suggests impending death.

PMID- 28501120
TI  - Histologic lung cancer subtype differentiates synchronous multiple primary lung
      adenocarcinomas from intrapulmonary metastases.
AB  - BACKGROUND: Distinguishing synchronous multiple primary lung cancers (SMPLCs)
      from intrapulmonary metastases is important. The objective of this study was to
      determine long-term survival in patients who underwent surgical resection for
      synchronous multiple lung cancers and identify additional criteria that may be
      useful to distinguish patients with SMPLCs from those with more advanced disease.
      METHODS: The medical records of patients with lung cancer who underwent planned
      resection for synchronous multiple lung cancers from 2007 to 2012 at our
      institutions were reviewed retrospectively. A comprehensive histologic assessment
      was used to determine whether the tumors were metastases or separate synchronous
      primary tumors. RESULTS: A total of 51 patients with synchronous multiple lung
      cancers underwent surgical resection. Twenty-nine patients had ipsilateral
      synchronous multiple lung cancers, and 22 had bilateral synchronous multiple lung
      cancers. No perioperative death occurred. The survival analysis of all 51
      patients with synchronous multiple lung cancers who underwent planned resection
      of all lesions showed 3- and 5-year overall survival rates of 86% and 67%,
      respectively, The median overall survival was not reached. The comprehensive
      histologic assessment identified six patients with intrapulmonary metastasis and
      45 patients with SMPLCs. Intrapulmonary metastases were associated with decreased
      survival. Among patients with SMPLCs, the epidermal growth factor receptor
      mutation distribution shown high concordant frequency rate of 35% (5/14).
      CONCLUSIONS: Survival after surgical resection of synchronous multiple lung
      cancers in different lobes was promising. A comprehensive histologic assessment
      was useful for differentiating SMPLCs from intrapulmonary metastases.

PMID- 28501121
TI  - Validation of a field spinal motion restriction protocol in a level I trauma
      center.
AB  - BACKGROUND: Spinal motion restriction (SMR) after traumatic injury has been a
      mainstay of prehospital trauma care for more than 3 decades. Recent guidelines
      recommend a selective approach with cervical spine clearance in the field when
      criteria are met. MATERIALS AND METHODS: In January 2014, the Department of
      Health Services of the City of Los Angeles, California, implemented revised
      guidelines for cervical SMR after blunt mechanism trauma. Adult patients (aged
      >=18 y) with an initial Glasgow Coma Scale (GCS) score of >=13 presented to a
      single level I trauma center after blunt mechanism trauma over the following 1-y
      period were retrospectively reviewed. Demographics, injury data, and prehospital
      data were collected. Cervical spine injury (CSI) was identified by International
      Classification of Disease, Ninth Revision, codes. RESULTS: Emergency medical
      services transported 1111 patients to the emergency department who sustained
      blunt trauma. Patients were excluded if they refused c-collar placement or if
      documentation was incomplete. A total of 997 patients were included in our
      analysis with 172 (17.2%) who were selective cleared of SMR per protocol. The
      rate of Spinal Cord Injury was 2.2% (22/997) overall and 1.2% (2/172) in patients
      without SMR. The sensitivity and specificity of the protocol are 90.9% (95%
      confidence interval: 69.4-98.4) and 17.4% (95% confidence interval: 15.1-20.0),
      respectively, for CSI. Patients with CSI who arrived without immobilization
      having met field clearance guidelines, were managed without intervention, and had
      no neurologic compromise. CONCLUSIONS: Guidelines for cervical SMR have high
      sensitivity and low specificity to identify CSI. When patients with injuries were
      not placed on motion restrictions, there were no negative clinical outcomes.

PMID- 28501123
TI  - Attenuation of intestinal ischemia-reperfusion-injury by beta-alanine: a
      potentially glycine-receptor mediated effect.
AB  - BACKGROUND: Acute mesenteric ischemia is often caused by embolization of the
      mesenteric arterial circulation. Coherent intestinal injury due to ischemia and
      following reperfusion get visible on macroscopic and histologic level. In
      previous studies, application of glycine caused an ameliorated intestinal damage
      after ischemia-reperfusion in rats. Because we speculated that glycine acted here
      as a signal molecule, we investigated whether the glycine-receptor agonist beta
      alanine evokes the same beneficial effect in intestinal ischemia-reperfusion.
      MATERIALS AND METHODS: beta-alanine (10, 30, and 100 mg/kg) was administered
      intravenously. Ischemia/reperfusion of the small intestine was initiated by
      occluding and reopening the superior mesenteric artery in rats. After 90 min of
      ischemia and 120 min of reperfusion, the intestine was analyzed with regard to
      macroscopic and histologic tissue damage, the activity of the saccharase, and
      accumulation of macrophages. In addition, systemic parameters and metabolic ones
      (e.g., acid-base balance, electrolytes, and blood glucose) were measured at
      certain points in time. RESULTS: All three dosages of beta-alanine did not change
      systemic parameters but prevent from hyponatremia during the period of
      reperfusion. Most importantly, application of 100-mg beta-alanine clearly
      diminished intestinal tissue damage, getting visible on macroscopic and
      histologic level. In addition, I/R-mediated decrease of saccharase activity and
      accumulation of macrophages in the small intestine were ameliorated. CONCLUSIONS:
      The present study demonstrated that beta-alanine was a potent agent to ameliorate
      I/R-induced injury of the small intestine. Due to its diminishing effect on the
      accumulation of macrophages, beta-alanine is strongly expected to mediate its
      beneficial effect via glycine receptors.

PMID- 28501122
TI  - Association of patient age with high-risk pathologic features in papillary
      thyroid cancer.
AB  - BACKGROUND: Certain patient demographics and histopathologic features are risk
      factors for papillary thyroid cancer (PTC) recurrence after initial treatment.
      Our objective was to determine whether very young age is associated with
      aggressive pathologic features in patients with PTC. MATERIALS AND METHODS: A
      retrospective analysis was performed for PTC patients who underwent surgical
      treatment at the University of Michigan between 2006 and 2012. Patients with
      known distant metastases were excluded. Demographics, high-risk pathologic
      features (capsular or vascular invasion, extrathyroidal extension, lymph node
      metastases, and extranodal extension), and disease recurrence were analyzed.
      RESULTS: 632 PTC patients were included in the analysis. Median age was 49 y
      (range 10-87). Tumors in patients aged <25 y had higher rates of extranodal
      extension (P = 0.002) compared with patients aged 25-44 y. Patients aged <25 y
      had more vascular invasion (P < 0.001) and lymph node metastasis (P = 0.001) than
      tumors in patients aged between 45-75 y. Patients aged >75 y had higher rates of
      vascular invasion (P < 0.001) and extrathyroidal extension (P = 0.001) compared
      with patients aged 45-75 y and more extrathyroidal extension (P < 0.001) than
      patients aged 25-44 y. There were no differences in tumor characteristics between
      the <25 and >75 age groups. CONCLUSIONS: PTC patients aged <25 y of age or older
      than 75 y exhibit higher rates of aggressive histopathologic features compared to
      PTC patients aged between 25-75 y.

PMID- 28501124
TI  - Effects of endotoxin absorber hemoperfusion on microcirculation in septic pigs.
AB  - BACKGROUND: Endotoxins contribute to systemic inflammatory response and
      microcirculatory dysfunctions under conditions of sepsis. Polymyxin B
      hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve
      clinical outcomes. This study aims to investigate the effect of PMX-HP on
      microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig
      model, we tested the hypothesis that PMX-HP can correct intestinal
      microcirculation, tissue oxygenation saturation, and histopathologic alterations.
      A total of 18 male pigs were divided into three groups: (1) sham; (2) sepsis
      (fecal peritonitis); and (3) sepsis + PMX-HP groups. A sidestream dark field
      video microscope was used to record microcirculation throughout the terminal
      ileal mucosa, colon mucosa, kidney surface, and sublingual area. A superficial
      tissue oxygenation monitor employing the light reflectance spectroscopy technique
      was used to measure the tissue oxygen saturation. Hematoxylin and eosin staining
      was used for histologic examination. RESULTS: The perfused small vessel density
      and tissue oxygen saturation of the ileal mucosa at 6 h were higher in the sepsis
      + PMX-HP group than those in the sepsis group. The fluid amount and
      norepinephrine infusion rate between the sepsis group and sepsis + PMX-HP groups
      did not differ significantly. The histologic score for the ileal mucosa was lower
      in the sepsis + PMX-HP group than that in the sepsis group. Finally, the urine
      output was higher in the sepsis + PMX-HP group than it was in the sepsis group.
      CONCLUSIONS: This study demonstrates that PMX-HP attenuates microcirculatory
      dysfunction, tissue desaturation, and histopathologic alterations in the ileal
      mucosa in septic pigs.

PMID- 28501125
TI  - Direct orthotopic implantation of hepatic organoids.
AB  - BACKGROUND: Liver organoids show potential for development as a tissue
      replacement therapy for patients with end-stage liver disease, but efficient
      methods for introducing organoids into host livers have not been established. In
      this study, we aimed to develop a surgical technique to implant hepatic organoids
      into the liver and assess their engraftment. METHODS: Donor hepatocytes were
      isolated from ROSA26 C57BL/6 mice, so that engrafted cells, when implanted into
      wild-type mice, could be easily identified by X-gal staining. Hepatic organoids
      were generated by three-dimensional culture in rotating wall vessel bioreactors.
      We qualitatively and quantitatively compared organoid engraftment to that of
      single-cell hepatocyte transplants. In addition, we determined the effect of
      adding stellate cells to hepatocytes to form co-aggregated organoids and the
      effect of partial hepatectomy of the host liver on organoid engraftment. RESULTS:
      Direct orthotopic implantation of hepatic organoids within a hepatotomy site
      resulted in local engraftment of exogenous hepatocytes with limited durability.
      Hepatocyte-stellate cell organoids produced more extracellular matrix but did not
      significantly improve engraftment compared with hepatocyte-alone organoids.
      Partial hepatectomy of the host liver led to significantly decreased engraftment
      of organoids. Survival of organoids was limited by the presence of apoptotic
      hepatocytes within organoids as early as 1 h after implantation. Organoids
      eventually became necrotic and elicited a chronic inflammatory giant cell
      reaction similar to a foreign body response. CONCLUSIONS: With additional
      organoid and host factor optimization, direct orthotopic implantation of hepatic
      organoids may be an approach to introduce large numbers of exogenous hepatocytes
      into recipient livers.

PMID- 28501126
TI  - Perceptions regarding helmet use: a cross-sectional survey of female pillions in
      Karachi, Pakistan.
AB  - BACKGROUND: In 2011, road traffic injury-associated fatalities among motorized
      two-wheeler (MTW) pillion riders (backseat two-wheeler passengers) rose 30% in
      Karachi. Despite mandatory helmet laws, helmet use fell 20% the same year. This
      study aims to identify opinions of female pillions on helmet usage and whether
      various forms of media influence their self-perception. METHODS: Trained
      surveyors, using a survey tool used in similar studies in South Asia, conducted
      random, man-on-the-street interviews of 400 women in four areas of Karachi. Data
      pertaining to demographics, opinions on helmet laws, media influences, and helmet
      usage were collected. Data were analyzed in SAS 9.3 using chi-squared or Fisher's
      exact tests. RESULTS: Of the 400 women, 98.8% (n = 394) reported never wearing a
      helmet while riding on a MTW as a pillion rider. Women with a postsecondary or
      higher (US ninth grade) education level were more likely to be aware of helmet
      laws (38.6%) than women with lower education levels (24.6%, P = 0.005). Most
      women (82.4%, n = 329) supported mandatory laws and 97% (n = 289) recognized that
      disability was the more likely to result than death in event of a traumatic brain
      injury. Nearly all (98.5%, n = 394) stated that they would use a helmet if they
      were men, regardless of age, education level, or employment status. Television
      news was the most influential media form (83.7%, n = 334), with most women
      finding it effective because of its informative nature (91.3%, n = 303).
      CONCLUSIONS: Most Pakistani women do not personally use helmets when riding MTWs,
      yet most believe helmet use should be legally required for MTW riders and
      drivers. These data show that media outlets such as television can be used as a
      platform to educate the public about helmet usage, which may lead to improved
      helmet compliance among female MTW pillions in Pakistan. Furthermore,
      investigations into improved helmet comfort and appearance by collaborating with
      helmet manufacturers may have a positive impact on helmet use in Pakistan.

PMID- 28501127
TI  - C-C motif chemokine 22 ligand (CCL22) concentrations in sera of gastric cancer
      patients are related to peritoneal metastasis and predict recurrence within one
      year after radical gastrectomy.
AB  - BACKGROUND: Gastric cancer is a common cancer with a poor prognosis. Chemokines
      play important roles in the tumor microenvironments to support tumor growth and
      metastasis. The effects of C-C motif chemokine ligand 22 (CCL22) in gastric
      cancer remain unclear. MATERIALS AND METHODS: Between January 1, 2014 and April
      31, 2014, a total of 298 gastric cancer patients were recruited to this study.
      Circulating concentrations of CCL22 were measured in gastric cancer patients
      before surgery, at discharged and during follow-up visits. The expression of
      CCL22 in gastric cancer tumor beds was measured by immunohistochemistry. The
      proportion of CD3+CD4+CD25+Foxp3+ regulatory T cells in tumor sites was assessed
      by flow cytometry. RESULTS: Gastric cancer patients had higher serum CCL22 levels
      compared to healthy controls (P < 0.001). Immunohistochemistry indicated that the
      gastric cancer tumor beds were the source of serum CCL22, as gastric cancer
      patients had an increased proportion of strong expression of CCL22 (P < 0.01),
      and immunohistochemistry scores were positively correlated with levels of
      circulating CCL22 (P < 0.001). Gastric cancer tissue harbored a higher percentage
      of regulatory T cells compared to normal tumor-free stomach margins (P < 0.001),
      and this abundance of regulatory T cells was positively correlated with
      circulating levels of CCL22 (P < 0.001). Gastric cancer patients with peritoneal
      metastasis showed increased levels of circulating CCL22 before surgery compared
      to metastasis-free patients (P < 0.001). Gastric cancer patients with the
      recurrence within the first year after surgery had elevated serum CCL22
      concentrations at different time points compared to those of recurrence-free
      patients (P < 0.001). Logistic regression analysis indicated that high CCL22
      circulating levels before surgery is a risk factor for peritoneal metastasis and
      an independent risk factor for an early recurrence after surgery. CONCLUSIONS:
      CCL22 plays an important role in supporting gastric cancer development presumably
      by increasing the percentage of regulatory T cells in the tumor
      microenvironments. CCL22 levels in sera have a predictive value for gastric
      cancer peritoneal metastasis and the early recurrence. Therefore, CCL22 may be a
      therapeutic target for gastric cancer.

PMID- 28501128
TI  - Immunochemotherapy benefits in gastric cancer patients stratified by programmed
      death-1 ligand-1.
AB  - BACKGROUND: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant
      chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1
      (PD-L1) has not been investigated. Investigating this might help in triaging
      candidates eligible to immunochemotherapy. MATERIALS AND METHODS: In total, 918
      patients with stages II and III gastric cancer, undergoing curative gastrectomy,
      and receiving adjuvant chemotherapy were enrolled in a prospective database, and
      the patients were retrospectively reviewed. We classified those patients into
      four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1,
      PSK (-,+); PD-L1, PSK (-,-); PD-L1, PSK (+,+); and PD-L1, PSK (+,-). In addition,
      another independent cohort of 20 patients undergoing radical gastrectomy was
      prospectively recruited to check their immunological cells of sera before and 2
      mo after PSK administration. RESULTS: PSK treatment was an independent prognostic
      factor for patient's overall survival (P = 0.020), whereas PD-L1 expression per
      se was not. Administration of PSK prolonged patient survival in stages IIIA and
      IIIB (P = 0.031) but not in stage II or stage IIIC. Patients with negative
      expression of PD-L1, treated with PSK had longer survival than those not treated
      with PSK (P = 0.033). PSK did not affect the survival of patients with positive
      expression of PD-L1, (P = 0.421). The percentages of natural killer and natural
      killer T (NKT) cells, but not Th1, Th17, Treg, or IFN-gamma+/CD8+ T cells, were
      significantly increased in PD-L1 (-) patients treated with PSK. However, these
      findings were not evident in PD-L1 (+) patients. CONCLUSIONS: PSK treatment
      preferentially confers a survival gain for patients with stage IIIA/IIIB gastric
      cancer, especially in the PD-L1 (-) subpopulation.

PMID- 28501129
TI  - Loss of muscle mass: a significant predictor of postoperative complications in
      acute diverticulitis.
AB  - BACKGROUND: Severe muscle mass depletion, sarcopenia, has been shown to be
      associated with poor operative outcomes. However, its impact on emergency
      abdominal operations remains unclear. The purpose of this study was to examine
      the association between low muscle mass (LMM) and outcomes after emergency
      operations for acute diverticulitis. PATIENTS AND METHODS: Patients >=18 y
      requiring an emergency operation for acute diverticulitis between January 2007
      and September 2014 were included. On preoperative computed tomography, the cross
      sectional area (CSA) and transverse diameter (TVD) of the right and left psoas
      muscle were measured at the level of the third lumbar vertebral body. Sensitivity
      analysis was performed to determine appropriate CSA and TVD cutoff values
      defining low skeletal muscle mass. Clinical outcomes of patients with low muscle
      mass (LMM group) were compared with the non-LMM group. RESULTS: A total of 89
      patients met our inclusion criteria. Median CSA and TVD were 794 mm2 and 24 mm,
      respectively. There was a strong correlation between the CSA and TVD (R2 = 0.84).
      In univariable analysis, significantly higher rates of postoperative major
      complications (63% versus 37%, P = 0.027) and surgical site infection (47% versus
      19%, P = 0.008) were identified in the LMM group. After adjusting for clinically
      important covariates in a logistic regression model, patients with LMM were
      significantly associated with higher odds of major complications and surgical
      site infection. CONCLUSIONS: Preoperative assessment of the psoas muscle CSA and
      TVD on computed tomography can be a practical method for identifying patients at
      risk for postoperative complications.

PMID- 28501131
TI  - MicroRNA-203 promotes liver regeneration after partial hepatectomy in cirrhotic
      rats.
AB  - BACKGROUND: Liver resection or partial hepatectomy (PH) is still the most
      commonly used therapeutic option for hepatocellular carcinoma (HCC) at present.
      However, the impaired regenerative ability induced by the accompanied liver
      cirrhosis is an important risk factor of posthepatectomy liver failure, and
      posthepatectomy liver failure is a feared complication that accounts for up to
      75% of mortality after extensive liver resection. MicroRNA(miR)-203 is a tumor
      suppressor of HCC and may act as a positive intermediary in A20-enhanced
      interleukin (IL-6)/signal transducer and activator of transcription 3 (STAT3) pro
      proliferative signals, which may promote liver regeneration after PH. However,
      its direct pro-proliferative effect on cirrhotic liver after hepatectomy is
      unknown. MATERIALS AND METHODS: Liver cirrhosis was induced by intraperitoneal
      injection of 50% CCl4-olive oil solution in adult male Wistar rat. Rats with
      liver cirrhosis received portal vein injection of physiological saline, miR-203
      lentivirus, or control empty lentivirus, and then 70% PH was performed under
      ether anesthesia 7 d later. Liver samples were harvested at 0, 24, 36, and 72 h
      after 70% PH. Hepatic expressions of cyclin D1 and Ki67 were checked to evaluate
      the liver regenerative ability. Hepatic expressions of IL-6, suppressor of
      cytokine signaling 3 (SOCS3), and phospho-STAT3 were also tested to clarify the
      mechanisms of miR-203 in liver regeneration. RESULTS: The regeneration of miR-203
      overexpression cirrhotic liver after 70% PH was enhanced and peaked at 24 and 36
      h after 70% PH. The cyclin D1-positive liver cells/high-power field (HPF) in miR
      203 overexpression liver markedly increased at 24 and 36 h after 70% PH compared
      with 0-h samples. When comparing with the control groups, cyclin D1-positive
      liver cells/HPF in miR-203 overexpression liver were also significantly increased
      at 24 and 36 h after 70% PH. A similar result of the Ki67-positive liver
      cells/HPF was achieved at 36 h after 70% PH. The hepatic expression of IL-6
      showed a rising tendency after 70% PH, and the levels of IL-6 are significantly
      higher in miR-203 overexpression livers. Hepatic expression of SOCS3 was
      negatively expressed with hepatic miR-203 expression level, and the reduced
      expression of SOCS3 facilitated the phosphorylation of STAT3. CONCLUSIONS: By
      targeting SOCS3 and then enhancing proliferating IL-6/STAT3 signaling pathway,
      hepatic overexpression of miR-203 can facilitate the initiation of liver
      regeneration and enhance the potency of liver regeneration after 70% PH in
      cirrhotic rat. Together with the tumor suppressive effect on HCC, miR-203 would
      be an ideal candidate for promoting liver regeneration in HCC patients undergoing
      liver resection without the risk of tumorigenesis or cancer recurrence.

PMID- 28501130
TI  - Collateral artery pathways of the femoral and popliteal artery.
AB  - BACKGROUND: The role of collateral artery circulation in the lower limb is under
      debate but clinically relevant, particularly when using covered stents for
      occlusive disease. Covered stents seem to outperform nitinol stents in extensive
      disease, but collaterals could be essential in case of acute thrombosis. In the
      present study, we describe the collateral pathways of the deep and superficial
      femoral artery (DFA, SFA) and the popliteal artery (PA), observed in human
      cadavers. METHODS: Ten fresh frozen cadaver legs were selected. The SFA and DFA
      were separately cannulated and injected with a different colored latex mixture
      simultaneously. After curing of the latex, the circulation was dissected thus
      visualizing the main arteries and their collateral vessels. The process was
      photographed and recorded, and collateral pathways were analyzed using a
      standardized vessel segmentation. The upper leg was divided in three regions,
      that is, the femoral triangle (F), the adductor canal (H), and the popliteal
      fossa (P) that, in turn, were split in three segments (1, 2, and 3, from proximal
      to distal). RESULTS: Overall, 113 collateral vessels were found; 69 originated
      from the DFA, 34 from the SFA, and 10 from the PA. The majority of collaterals
      originating from the DFA terminated in the SFA (57%). Fifty-six of 113
      collaterals (50%) ended in either the distal adductor channel (H3) or the
      proximal PA (P1). Another 28 collateral arteries (25%) had their origin in this
      segment (H3, P1) and mostly connected to the P2 and P3 segments. Forty-three
      collaterals of the DFA and H3 segment had a direct or indirect connection to
      below the knee muscles. CONCLUSIONS: The majority of collaterals originate from
      the DFA, and the greater part of all collaterals has a connection with the H3-P1
      segment. This observation may have clinical implications in the planning of
      endovascular procedures.

PMID- 28501132
TI  - Association between climatic elements and acute appendicitis in Japan.
AB  - BACKGROUND: In Japan, it has been reported that an increase in atmospheric
      pressure is associated with a higher incidence of acute appendicitis. The aim of
      this epidemiologic study was to investigate the association between climatic
      elements and the incidence of acute appendicitis. MATERIALS AND METHODS: A case
      crossover design was used in the present study. Two wk before diagnosis was used
      for the target period. The same 2-wk period, but 1, 2, and 3 y before diagnosis,
      was used for the control period. The study participants were patients with acute
      appendicitis (10-29 y) from 14 facilities in the Greater Tokyo Area. Mean of the
      observed values for atmospheric pressure, temperature, relative humidity, and
      hours of sunshine calculated for each target and control period were used as
      climatic elements to investigate trends 1 and 2 wk before diagnosis. RESULTS: The
      year of diagnosis, a statistically significant moderate upward trend in
      atmospheric pressure was observed during the 2-wk period before diagnosis of
      acute appendicitis (tau = 0.47; P = 0.0213), whereas a weak nonsignificant
      downward trend was observed 1 y before diagnosis (tau = -0.29; P = 0.1596), and
      weak nonsignificant upward trends were observed 2 (tau = 0.24; P = 0.2505) and 3
      y (tau = 0.28; P = 0.1634) before diagnosis. CONCLUSIONS: An association was
      found between atmospheric pressure and the incidence of acute appendicitis.
      However, no significant differences were found in relation to sex or age. These
      findings suggest that changes in atmospheric pressure are associated with the
      likelihood of patients visiting the hospital.

PMID- 28501133
TI  - Intraintestinal administration of ulinastatin protects against sepsis by
      relieving intestinal damage.
AB  - BACKGROUND: Intravenous administration of ulinastatin (UTI), a broad spectral
      protease inhibitor, has been used on an experimental basis with severe sepsis
      patients in Asia. However, the effects of intraintestinal administration of UTI
      on intestinal and multiple organ damage in sepsis have not been reported.
      MATERIALS AND METHODS: In this study, we established a sepsis model in rats using
      cecal ligation and puncture and compared the effects of intraintestinal
      administration of UTI through an artificial fistula of duodenum and
      intraperitoneal administration of UTI on the pathophysiological changes of
      sepsis. RESULTS: It was found that intraintestinal administration of UTI (1)
      significantly improved the survival of septic rats, (2) significantly reduced the
      serum levels of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 as
      well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and
      fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal
      microscopic and ultrastructural damage of septic rats. In addition, the
      protective effects of intraintestinal administration of UTI were significantly
      better than those of intraperitoneal administration of UTI. CONCLUSIONS: Overall,
      the present study for the first time revealed that intraintestinal administration
      of protease inhibitor UTI could reduce systemic inflammatory responses and
      multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of
      intestinal wall due to proteases and provided new research ideas and experimental
      evidences for treatment of sepsis by intraintestinal administration of UTI.

PMID- 28501135
TI  - Impact of hernia volume on pulmonary complications following complex hernia
      repair.
AB  - BACKGROUND: Despite a multitude of evidence-based prediction models and risk
      factors for postoperative complications after ventral hernia repair, estimating a
      patient's risk of postoperative complications after ventral hernia repair remains
      challenging. In an attempt to improve the preoperative assessment of complex
      hernia patients, some studies have examined pulmonary changes after hernia repair
      hypothesizing that large hernias lead to pulmonary changes and increased
      pulmonary complication rates. Some studies have described a correlation between
      hernia volume and pulmonary changes, although none provided compelling evidence
      to identify hernia volume as a risk factor for pulmonary complications. This
      study evaluates the relationship between hernia volume and postoperative
      pulmonary complications using computed tomography (CT)-based volume measurements.
      MATERIALS AND METHODS: Analysis of a prospectively maintained database of
      consecutive complex hernia patients from 2011 to 2014 undergoing endoscopic
      (ECST) or open component separation technique (CST) for a hernia defect with a
      minimum width of 6 cm and visual protrusion of the hernia sac ventral of the
      rectus abdominis muscles in supine position was performed. Hernia volume was
      calculated using multiple plane reconstruction of a standard abdominal CT-scan.
      Noted endpoints were pulmonary complications. RESULTS: Thirty-five patients
      underwent ECST (n = 20) or CST (n = 15) with a median defect volume of 474 cm3
      (range, 114-2086 cm3). Observed complications were pneumonia (n = 4), pulmonary
      infiltrate (n = 3), aspiration pneumonia (n = 2), and acute respiratory distress
      syndrome (n = 1). Univariate and multivariate analyses showed that pulmonary
      complications were associated with "hernia volume" (P = 0.045; 95% CI: 1.008
      1.910). CONCLUSIONS: Hernia volume is a promising risk factor for postoperative
      pulmonary complications and can be calculated using a standard abdominal CT-scan.

PMID- 28501134
TI  - Factors associated with palliative care use in patients undergoing cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Peritoneal carcinomatosis represents widespread metastatic disease
      throughout the abdomen and/or pelvis. Cytoreductive surgery/hyperthermic
      intraperitoneal chemotherapy (CRS/HIPEC) improves the overall survival compared
      to standard therapy alone. The role palliative care (PC) plays however, remains
      poorly studied among these patients. METHODS: Patients who had previously
      undergone HIPEC and who underwent an inpatient admission from 7/1/2013 to
      6/30/2014 were identified to determine which patients were referred for inpatient
      or outpatient palliative consultation. Multivariable logistic regression analysis
      was performed to identify risk factors associated with the use of PC. RESULTS: Of
      the 60 patients analyzed, 23 (38.3%) had a PC consultation with a median time to
      PC referral of 310 (IQR: 151-484 days). Patients who were prescribed opioids (no
      PC referral versus PC referral: 46.0% versus 91.3%, P < 0.001), patients who
      reported the use of a cancer-related emetic (35.1% versus 87.0%, P < 0.001),
      patients reporting the use of total parenteral nutrition (16.2% versus 39.1%, P =
      0.046), and patients dependent on a gastric tube for nutrition (5.4% versus
      43.5%, P < 0.001) were more likely to be referred to a PC consultation. On
      multivariable analysis, use of opioids, use of a cancer-related antiemetic, and
      the use of a G-tube were independently associated with a greater odds for being
      referred to PC (all P < 0.05). CONCLUSIONS: Approximately one-third of patients
      were referred to PC following cytoreductive surgery/hyperthermic intraperitoneal
      chemotherapy. Palliative care referrals were most commonly used for patients with
      chronic symptoms, which are difficult to manage, especially toward the end of
      life.

PMID- 28501136
TI  - Delayed splenic vascular injury after nonoperative management of blunt splenic
      trauma.
AB  - BACKGROUND: Delayed splenic vascular injury (DSVI) is traditionally considered a
      rare, often clinically occult, harbinger of splenic rupture in patients with
      splenic trauma that are managed conservatively. The purpose of our study was to
      assess the incidence of DSVI and associated features in patients admitted with
      blunt splenic trauma and managed nonoperatively. MATERIALS AND METHODS: A
      retrospective analysis was conducted over a 4-y time. Patients admitted with
      blunt splenic trauma, managed no-operatively and with a follow-up contrast
      enhanced computed tomography (CT) scan study during admission were included. The
      CT scans were reviewed for American Association for the Surgery of Trauma splenic
      injury score, amount of hemoperitoneum, and presence of DSVI. Logistic regression
      models were used to investigate the risk factors associated with DSVI. RESULTS: A
      total of 100 patients (60 men and 40 women) constituted the study group. Follow
      up CT scan demonstrated a 23% incidence of DSVI. Splenic artery angiography
      validated DSVI in 15% of the total patient population. Most DSVIs were detected
      only on arterial phase CT scan imaging. The American Association for the Surgery
      of Trauma splenic injury score (odds ratio = 1.73; P = 0.045) and the amount of
      hemoperitoneum (odds ratio = 1.90; P = 0.023) on admission CT scan were
      associated with the development of DSVI on follow-up CT scan. CONCLUSIONS: DSVI
      on follow-up CT scan imaging of patients managed nonoperatively after splenic
      injury is common and associated with splenic injury score assessed on admission
      CT scan.

PMID- 28501137
TI  - Supinator to ulnar nerve transfer via in situ anterior interosseous nerve bridge
      to restore intrinsic muscle function in combined proximal median and ulnar nerve
      injury: a novel cadaveric study.
AB  - BACKGROUND: In cases of high ulnar nerve palsy, result of nerve repair in term of
      intrinsic muscle recovery is unsatisfactory. Distal nerve transfer can diminish
      the regeneration time and improve the results. But, there was no perfect distal
      nerve transfer for restoring intrinsic hand function in combined proximal median
      and ulnar nerve injuries. This cadaveric study aims to evaluate the possibility
      and feasibility of supinator nerve transfer to motor branch of ulnar nerve (MUN).
      METHODS: Ten cadaveric upper limbs dissected to identify the location of the
      supinator branch, anterior interosseous nerve (AIN), and MUN. The AIN was cut
      from its origin and transferred to the supinator branches. Also, the AIN was
      distally cut and transferred to the MUN. After nerve coaptation, surface area,
      fascicle count, and axon number were determined by histologic methods. RESULTS:
      In all limbs, the proximal and distal stumps of AIN reached the supinator branch
      and the MUN without tension, respectively. The mean of axon number in the
      supinator, proximal stump of AIN, distal stump of AIN and MUN branches were
      32,426, 45,542, 25,288, and 35,426, respectively. CONCLUSIONS: This study showed
      that transfer of the supinator branches to the MUN is possible via the in situ
      AIN bridge. The axon count data showed a favorable match between the supinator
      branches, AIN, and MUN. Therefore, it is suggested that this technique can be
      useful for patients with combined high median and ulnar nerve injuries.

PMID- 28501138
TI  - Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat
      experimental colitis.
AB  - The aim of this study was to evaluate the effect of ulcerative colitis on the
      submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6
      Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon
      to induce ulcerative colitis, and distal colons were collected after 24h. The
      colitis rats were compared with those in the sham and control groups. Double
      labelling of the P2X7 receptor with calbindin (marker for intrinsic primary
      afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and
      vasodilator neurons of the submucosal plexus), HuC/D and S100beta was performed
      in the submucosal plexus. The density (neurons per area) of submucosal neurons
      positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%,
      34%, 8.2% and 28%, respectively, in the treated group. In addition, the density
      of enteric glial cells in the submucosal plexus decreased by 33%. The profile
      areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis
      revealed increased lamina propria and decreased collagen in the colitis group.
      This study demonstrated that ulcerative colitis affected secretory and
      vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing
      the P2X7 receptor.

PMID- 28501139
TI  - J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer.

PMID- 28501141
TI  - TRPV6: From identification to function.

PMID- 28501140
TI  - Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung
      cancer (J-ALEX): an open-label, randomised phase 3 trial.
AB  - BACKGROUND: Alectinib, a potent, highly selective, CNS-active inhibitor of
      anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in
      the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive
      non-small-cell lung cancer. Given those promising results, we did a phase 3 trial
      to directly compare the efficacy and safety of alectinib and crizotinib. METHODS:
      J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor
      naive Japanese patients with ALK-positive non-small-cell lung cancer, who were
      chemotherapy-naive or had received one previous chemotherapy regimen, from 41
      study sites in Japan. Patients were randomly assigned (1:1) via an interactive
      web response system using a permuted-block method stratified by Eastern
      Cooperative Oncology Group performance status, treatment line, and disease stage
      to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily
      until progressive disease, unacceptable toxicity, death, or withdrawal. The
      primary endpoint was progression-free survival assessed by an independent review
      facility. The efficacy analysis was done in the intention-to-treat population,
      and safety analyses were done in all patients who received at least one dose of
      the study drug. The study is ongoing and patient recruitment is closed. This
      study is registered with the Japan Pharmaceutical Information Center (number
      JapicCTI-132316). FINDINGS: Between Nov 18, 2013, and Aug 4, 2015, 207 patients
      were recruited and assigned to the alectinib (n=103) or crizotinib (n=104)
      groups. At data cutoff for the second interim analysis, 24 patients in the
      alectinib group had discontinued treatment compared with 61 in the crizotinib
      group, mostly due to lack of efficacy or adverse events. At the second interim
      analysis (data cutoff date Dec 3, 2015), an independent data monitoring committee
      determined that the primary endpoint of the study had been met (hazard ratio 0.34
      [99.7% CI 0.17-0.71], stratified log-rank p<0.0001) and recommended an immediate
      release of the data. Median progression-free survival had not yet been reached
      with alectinib (95% CI 20.3-not estimated) and was 10.2 months (8.2-12.0) with
      crizotinib. Grade 3 or 4 adverse events occurred at a greater frequency with
      crizotinib (54 [52%] of 104) than alectinib (27 [26%] of 103). Dose interruptions
      due to adverse events were also more prevalent with crizotinib (77 [74%] of 104)
      than with alectinib (30 [29%] of 103), and more patients receiving crizotinib (21
      [20%]) than alectinib (nine [9%]) discontinued the study drug because of an
      adverse event. No adverse events with a fatal outcome occurred in either
      treatment group. INTERPRETATION: These results provide the first head-to-head
      comparison of alectinib and crizotinib and have the potential to change the
      standard of care for the first-line treatment of ALK-positive non-small-cell lung
      cancer. The dose of alectinib (300 mg twice daily) used in this study is lower
      than the approved dose in countries other than Japan; however, this limitation is
      being addressed in the ongoing ALEX study. FUNDING: Chugai Pharmaceutical Co,
      Ltd.

PMID- 28501142
TI  - ?
AB  - Jean-Martin Charcot (1825-1893) was the preeminent neurologist of the nineteenth
      century. Several of his major contributions remain fully relevant to contemporary
      neurology, and this essay highlights three areas of particular importance to the
      modern neurologist: the anatomo-clinical method that Charcot developed as the
      anchor of neurological study; the integration of new scientific discoveries from
      other fields as a core strategy for neurological advancement; and the role of
      heredity as the fundamental etiological focus to the understanding of the
      pathogenesis of primary neurological disorders. Further, Charcot left a strong
      tradition of visual skills as the core requirement for accurate neurological
      diagnosis and emphasized scientific humility in the face of difficult diseases.
      In spite of vast advances in neuroscience over the 20th and 21st centuries, the
      challenges faced by Charcot remain largely the same for the contemporary
      neurologist, and the lessons provided by Charcot retain their power and
      significance today.

PMID- 28501143
TI  - Do we know how to diagnose epilepsy early in Alzheimer's disease?
AB  - Epilepsy is an increasingly recognized comorbidity in Alzheimer's disease (AD).
      First described as generalized in dementia patients, epileptic AD patients are
      nowadays fully described in earlier stages of the disease (with mild or
      subjective cognitive impairment). At such early stages, patients may present not
      only with generalized seizures, but also with focal seizures (commonly localized
      in the frontal or temporal lobe). Thus, partial or generalized epilepsy is part
      of the semiological spectrum of AD that should be borne in mind at all stages of
      disease to ensure early identification and prevent the risk of repeated seizures
      (such as accidents, injury, progression of cognitive impairment). This review of
      the available (and still growing) literature shows that there are already
      sufficient data to inform physicians on seizure semiology, and on the diagnostic
      value of electroencephalography and brain imaging. Taken together, these tools
      can help to rapidly identify epilepsy in AD patients. Nevertheless, epilepsy
      diagnosis can be challenging, and test medication is sometimes necessary. Some
      cerebrospinal fluid biomarkers (or their ratios) may also prove to be good
      predictors of seizures in AD, but further studies are needed. Epilepsy in AD
      patients is frequently pharmacosensitive, and a good response can be obtained
      with standard doses of antiepileptic drugs. For all these reasons and based on
      our review of the literature, it appears that, at present, the diagnosis of
      epilepsy in AD is not only possible at any stage of the disease, but also to be
      recommended to improve the patient's prognosis.

PMID- 28501144
TI  - Sequential injection differential pulse voltammetric method based on screen
      printed carbon electrode modified with carbon nanotube/Nafion for sensitive
      determination of paraquat.
AB  - The screen-printed carbon electrode (SPCE) modified with various nanoparticles
      has been studied for using as a working electrode in voltammetric technique. The
      electrochemical behavior of paraquat on different electrodes was studied by
      cyclic voltammetry (CV), and then differential pulse voltammetry (DPV) has been
      employed for trace analysis of paraquat based on redox reaction which the peak
      current was directly proportional to the concentration of paraquat in the
      solution. The SPCE modified with carbon nanotube dispersed in Nafion and ethanol
      (SPCE-CNT/Nafion) gave the best result. Sequential injection-differential pulse
      voltammetric (SI-DPV) method has been developed for more automated analysis and
      to reduce chemical consumption. The parameters affecting the SI-DPV system such
      as step potential, modulation amplitude, flow rate, and concentration of sodium
      chloride as an electrolyte were studied to improve the sensitivity. Under the
      optimum condition of the system, i.e., Nafion concentration of 1% (w/v), volume
      of CNT suspension of 2uL, flow rate of 100uLs-1, step potential of 5mV,
      modulation amplitude of 100mV and concentration of sodium chloride of 1M, a
      linear calibration graph in the range of 0.54-4.30uM with a good R2 of 0.9955 and
      a limit of detection of 0.17uM (0.03mgL-1) were achieved. The proposed system
      shows high tolerance to some possible interfering ions in natural water,
      surfactant, and other pesticides. The relative standard deviation (RSD) was 4.2%
      for 11 replicate measurements with the same electrode. The reproducibility for
      the preparation of 7 modified electrodes was 2.3% RSD. Recoveries of the analysis
      were obtained in the range of 82-106%. The developed system can be conveniently
      applied for analysis without pretreatment of the samples.

PMID- 28501145
TI  - A novel "turn-on" thiooxofluorescein-based colorimetric and fluorescent sensor
      for Hg2+ and its application in living cells.
AB  - A novel water-soluble fluorescent probe FLS2 based on the thiooxofluorescein
      derivative has been firstly designed and synthesized. UV-vis absorption and
      fluorescence spectra studies showed that the FLS2 as a colorimetric and
      ratiometric fluorescent probe exhibited high selectivity and sensitivity towards
      Hg2+, which was mainly attributed to the special binding with the receptor unit
      accompanied with the spirolactam ring-opening progress. In addition, the probe
      FLS2 could be used as a naked-eye indicator for Hg2+ with reversible response. It
      displayed approximate 37-fold fluorescent enhancement at 529nm in the presence of
      only 2.0 equiv. Hg2+ and the detection limit was calculated at about 39nM. What's
      more, cellular imaging experiment revealed that the sensor had excellent
      biocompatibility and low cytotoxicity that could be utilized for monitoring Hg2+
      in living cells.

PMID- 28501146
TI  - Selective solid phase extraction of chloroacetamide herbicides from environmental
      water samples by amphiphilic magnetic molecularly imprinted polymers.
AB  - In this study, a novel amphiphilic magnetic molecularly imprinted polymers
      (MMIPs) have been prepared by using Fe3O4 microspheres as the magnetic core, 4
      vinyl pyridine (4-VP) and alkenyl glycosides glucose (AGG) as functional co
      monomers. Fe3O4 microspheres were directly encapsulated by the polymer without
      any surface modification in the distillation-precipitation polymerization. The
      morphology and composition of MMIPs were characterized by X-ray diffraction
      (XRD), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM),
      and transmission electron microscopy (TEM). Binding property and magnetic
      separation ability were systematically investigated through the equilibrium
      binding experiments. The feasibility of magnetic molecular imprinted solid phase
      extraction (MMISPE) was investigated for the selective enrichment of
      chloroacetamide herbicides from environmental water samples. The developed MMISPE
      HPLC method exhibited good linearity (0.1-200MUgL-1), low limit of detection
      (0.03-0.06MUgL-1), and good precision (RSD<7%) under the optimized conditions.
      The introduced MMISPE-HPLC method was successfully used to analyze
      chloroacetamide herbicides in environmental water samples. Spiked chloroacetamide
      herbicides recoveries in three water samples ranged from 82.1% to 102.9%. These
      results indicated that amphiphilic MMIPs were the promising sorbents for the
      selective enrichment of chloroacetamide herbicides at trace levels from real
      environmental water samples.

PMID- 28501147
TI  - A fluorescent homogeneous assay for myeloperoxidase measurement in biological
      samples. A positive correlation between myeloperoxidase-generated HOCl level and
      oxidative status in STZ-diabetic rats.
AB  - Myeloperoxidase (MPO) is a key enzyme derived from leukocytes which is associated
      with the initiation and progression of many inflammatory diseases. Increased
      levels of MPO may contribute to cellular dysfunction and tissues injury by
      producing highly reactive oxidants such as hypochlorous acid (HOCl).
      Myeloperoxidase-generated HOCl is therefore considered as a relevant biomarker of
      oxidative stress-related damage and its quantitation is of great importance to
      the study of disease progression. In this context, the current study describes a
      rapid, sensitive and homogeneous fluorescence-based method for detecting the MPO
      chlorination activity in biological samples. This assay utilizes 7-hydroxy-2-oxo
      2H-chromene-8-carbaldehyde oxime as a selective probe for HOCl detection, and is
      adapted to 96-well microplates to allow high-throughput quantitation of active
      MPO. The ability of the method to monitor HOCl release was further investigated
      in hyperglycemic streptozotocin-treated diabetic rats. The data proved that the
      present assay has a reliable performance when quantitating the active MPO in the
      plasma of diabetic animals, a feature of inflammatory disease found concomitant
      with an elevation of protein carbonyls levels and lipid peroxidation and which
      was negatively correlated with the ratio of reduced-to-oxidized glutathione.

PMID- 28501148
TI  - Simultaneous determination of acidic phytohormones in cucumbers and green bean
      sprouts by ion-pair stir bar sorptive extraction-high performance liquid
      chromatography.
AB  - A simple, sensitive and inexpensive method of ion-pair stir bar sorptive
      extraction (IP-SBSE) combined with high performance liquid chromatography 
      ultraviolet (HPLC-UV) detection was developed for the simultaneous determination
      of three acidic phytohormones (salicylic acid (SA), indole-3-acetic acid (IAA),
      and abscisic acid (ABA)) in vegetables. With the addition of cationic surfactant
      cetyltrimethylammonium bromide (CTAB) in sample solutions, ion pair between CTAB
      and target phytohormones were formed, leading to an improvement of the extraction
      efficiency for target phytohormones by C18 silica coated SBSE. The factors
      affecting the extraction efficiency of three target phytohormones by IP-C18
      coated SBSE were optimized, and the optimal experimental conditions were
      established. Under the optimal conditions, the limits of detection for SA, IAA
      and ABA obtained by IP-C18-SBSE-HPLC-UV were 2.7, 2.1 and 0.3MUgL-1, with the
      relative standard deviations of 6.0%, 5.0% and 8.3%, respectively, and the
      enrichment factor was 32-49-fold. The developed method was applied to the
      determination of SA, IAA and ABA in cucumbers and green bean sprouts, and the
      recoveries of SA, IAA and ABA for the spiked samples were between 72.8% and
      109.5%.

PMID- 28501149
TI  - Novel cellulose-based halochromic test strips for naked-eye detection of alkaline
      vapors and analytes.
AB  - A simple, portable and highly sensitive naked-eye test strip is successfully
      prepared for optical detection of gaseous and aqueous alkaline analytes. Novel pH
      sensory tricyanofuran-hydrazone (TCFH) disperse colorant containing a hydrazone
      recognition functional moiety is successfully synthesized via azo-coupling
      reaction between active methyl-containing tricyanofuran (TCF) heterocycle and
      diazonium salt of 4-aminobenzaldehyde followed by Knoevenagel condensation with
      malononitrile. UV-vis absorption spectra display solvatochromism and reversible
      color changes of the TCFH solution in dimethyl sulfoxide in response to pH
      variations. We investigate the preparation of hydrophobic cellulose/polyethylene
      terephthalate composites characterized by their high affinity for disperse dyes.
      Composite films made from CA, Cell/CA, PET/CA, and Cell/PET-CA are produced via
      solvent-casting procedure using 10-30% modified cellulose or modified
      polyethylene terephthalate. The mechanical properties and morphologies of these
      composite films are investigated. The prepared pH-sensory hydrazone-based
      disperse dye is then applied to dye the produced cellulose-based composite films
      employing the high temperature pressure dyeing procedure. The produced
      halochromic PET-CA-TCFH test strip provide an instant visible signal from orange
      to purple upon exposure to alkaline conditions as proved by the coloration
      measurements. The sensor strip exhibits high sensitivity and quick detection
      toward ammonia in both of aqueous and vapor phases by naked-eye observations at
      room temperature and atmospheric pressure.

PMID- 28501150
TI  - Facile one-pot fabrication of Ag@MOF(Ag) nanocomposites for highly selective
      detection of 2,4,6-trinitrophenol in aqueous phase.
AB  - Ag@MOF(Ag) nano-composites were fabricated through one-pot facile reflux reaction
      from the raw materials of AgNO3 and 2-aminoterephthalic acid, and were then
      characterized through SEM, TEM, XRD, XPS, and FTIR, which showed a high
      fluorescence quantum yield (10.6%) and exhibited outstanding selectivity and
      excellent sensitivity for 2,4,6-trinitrophenol (TNP) over a concentration range
      of 1-29MUM in water. The fluorescence quenching mechanism may be attributed to
      hydrogen-bonding interactions and resonance energy transfer.

PMID- 28501151
TI  - Micro-sampling method based on high-resolution continuum source graphite furnace
      atomic absorption spectrometry for calcium determination in blood and
      mitochondrial suspensions.
AB  - A micro-sampling and straightforward method based on high resolution continuum
      source atomic absorption spectrometry (HR-CS AAS) was developed to determine
      extracellular and intracellular Ca in samples of interest in clinical and
      biomedical analysis. Solid sampling platforms were used to introduce the micro
      samples into the graphite furnace atomizer. The secondary absorption line for Ca,
      located at 239.856nm, was selected to carry out the measurements. Experimental
      parameters such as pyrolysis and atomization temperatures and the amount of
      sample introduced for the measurements were optimized. Calibration was performed
      using aqueous standards and the approach to measure at the wings of the
      absorption lines was employed for the expansion of the linear response range. The
      limit of detection was of 0.02mgL-1 Ca (0.39ng Ca) and the upper limit of linear
      range was increased up to 8.0mgL-1 Ca (160ng Ca). The proposed method was used to
      determine Ca in mitochondrial suspensions and whole blood samples with successful
      results. Adequate recoveries (within 91-107%) were obtained in the tests
      performed for validation purposes.

PMID- 28501153
TI  - Faradaic and capacitive current estimation by means of Independent Components
      Analysis and 1kHz sampling.
AB  - In this work it was demonstrated for the first time that Independent Components
      Analysis non-deterministic multivariate strategy enables estimation of the
      Faradic and double layer charging current components in differential pulse and
      anodic stripping voltammetry. The signals separation can be realized based on the
      different shapes of the capacitive and Faradaic current functions. The set of
      calibration voltammograms measured with the 1kHz sampling frequency is the
      sufficient data to retrieve signals compatible with the theoretical shapes, with
      r2 greater than 0.987 for Faradaic component and greater than 0.994 for
      capacitive component. In the effect, DP voltammograms of Pb(II) and Cd(II)
      recorded on silver annular band electrode were constructed using only Faradaic
      component. Quantitative analysis was performed and calibration models were
      calculated by different waiting time and sampling time, what demonstrated the
      possibility of significant improvement of sensitivity in considered experiments.

PMID- 28501152
TI  - Determination of inorganic arsenic in algae using bromine halogenation and on
      line nonpolar solid phase extraction followed by hydride generation atomic
      fluorescence spectrometry.
AB  - Accurate, stable and fast analysis of toxic inorganic arsenic (iAs) in
      complicated and arsenosugar-rich algae matrix is always a challenge. Herein, a
      novel analytical method for iAs in algae was reported, using bromine halogenation
      and on-line nonpolar solid phase extraction (SPE) followed by hydride generation
      atomic fluorescence spectrometry (HG-AFS). The separation of iAs from algae was
      first performed by nonpolar SPE sorbent using Br- for arsenic halogenation. Algae
      samples were extracted with 1% perchloric acid. Then, 1.5mL extract was reduced
      by 1% thiourea, and simultaneously reacted (for 30min) with 50MUL of 10% KBr for
      converting iAs to AsBr3 after adding 3.5mL of 70% HCl to 5mL. A polystyrene (PS)
      resin cartridge was employed to retain arsenicals, which were hydrolyzed, eluted
      from the PS resin with H2O, and categorized as iAs. The total iAs was quantified
      by HG-AFS. Under optimum conditions, the spiked recoveries of iAs in real algae
      samples were in the 82-96% range, and the method achieved a desirable limit of
      detection of 3MUgkg-1. The inter-day relative standard deviations were 4.5% and
      4.1% for spiked 100 and 500MUgkg-1 respectively, which proved acceptable for this
      method. For real algae samples analysis, the highest presence of iAs was found in
      sargassum fusiforme, followed by kelp, seaweed and laver.

PMID- 28501154
TI  - New approach to H-point standard addition method for detection and elimination of
      unspecific interferences in samples with unknown matrix.
AB  - A novel method for correction of unknown unspecific (additive) interferences was
      developed in sequential injection analysis (SIA) using a Lab on Valve module
      (LOV) with spectrophotometric detection. The method implements a novel idea to
      calibrate by the standard addition method in several different chemical
      conditions created in such a way to measure different signal for an analyte and
      unchanged signal for interferents causing additive effect. This approach, being
      an enhancement of the H-point standard addition method (HPSAM), enables to
      quantify unbiased concentration of an analyte in the presence of unknown
      interferences. The method was tested on the example of the determination of
      ascorbic acid in soft drinks and juices basing on reduction of Fe(III) to Fe(II)
      and reaction of the latter with o-phenanthroline to the ferroin complex absorbing
      at 512.0nm. The analytical utility of the method has been verified and confirmed
      by the spectrophotometric determination of total acidity in rose and red wines in
      the presence of bromothymol blue absorbing at 616.0nm. Calibration solutions were
      prepared automatically in the designed flow system. Ascorbic acid was determined
      with LOD of 1.4mgL-1 and LOQ of 4.2mgL-1 within linear working range up to 80mgL
      1, while in case of the determination of total acidity the values of 4.2, 11.8
      and 100, respectively, were obtained. A sample was consumed in volumes of 400 and
      1000uL in both cases. The analyses are simple, "green", and non-expensive. The
      developed method is readily applicable to analysis of real samples of complex
      unknown matrices and adaptable to different analytical methods.

PMID- 28501155
TI  - Morphology-tunable polydopamine nanoparticles and their application in Fe3+
      detection.
AB  - In this work, we discovered the morphology transformation property of
      polydopamine (PDA) nanomaterials, the addition of Fe3+ initiated the dramatic
      morphology transformation of PDA dots from aggregated plate-like to uniform
      willow-leaf-like morphology. Further study revealed that this fascinating
      morphology transformation process could be attributed to the oxidative nature and
      coordination characteristic of Fe3+. This is the first report on the morphology
      transformation ability of PDA, and a probable self-assembled mechanism was
      proposed to explain this issue. Besides, we noticed that morphological and
      fluorescent properties of PDA dots were closely related, thus a fluorescent Fe3+
      detection method was presented based on the morphology-tunable PDA dots. With the
      proposed method, selective Fe3+ detection was achieved with a wide linear dynamic
      range of 10MUM to 1mM. Furthermore, since the morphology tuning behavior of PDA
      dots was easy to operate, we anticipate this ability will find significant
      utility in sensing, drug delivery, and tissue engineering.

PMID- 28501156
TI  - Broadcasting photonic lab on a chip concept through a low cost manufacturing
      approach.
AB  - A low cost fabrication process for photonic lab on a chip systems is here
      proposed. For the implementation of the masters suitable for cast molding
      fabrication, an inexpensive dry film photoresist, patternable using standard
      laboratory equipment, is benchmarked against standardized SU-8 masters obtained
      using UV lithography and systems manufacture in clean room facilities. Results
      show adequate system fabrication and a comparable performance of the photonic
      structures for absorbance/extinction measurements.

PMID- 28501157
TI  - pH-Triggered Disaggregation-Induced Emission (DIE) probe for sensoring minor-pH
      changes in near infrared fluorescence region.
AB  - A new strategy for pH-responsive near infrared (NIR) cyanine dye, based on the
      concept of triggered disaggregation-induced emission (DIE), has been developed.
      Schiff base group was introduced to the molecular scaffold of Cy7, and promoted
      the aggregation of cyanine in pH7.4 buffer due to the strong pi-pi interaction.
      While in an acidic (pH 5.8) environment, the Schiff base group was hydrolyzed by
      acid and the nanoparticles were disaggregated. The vanishing of the
      intermolecular aggregation-caused quenching thus induced a fluorescence recovery
      of 96 folds. Moreover, abundant kinds of Schiff base provide more potential
      cyanine dyes for pH-responsive ultrahigh NIR fluorescence "Off/On" ratio, which
      could work as the intelligent bio-imaging probes in near future.

PMID- 28501158
TI  - Poly(vinyl alcohol) capped silver nanoparticles for antioxidant assay based on
      seed-mediated nanoparticle growth.
AB  - A simple and rapid method for measurement of total antioxidant capacity (TAC) was
      developed. In this work, gallic acid was used as the antioxidant standard.
      Poly(vinyl alcohol) embedded silver nanoparticles (PVA-AgNPs) were employed as a
      colorimetric sensor. The detection principle was based on the seed-mediated
      nanoparticle growth technique. The PVA-AgNPs act as a catalyst in the reduction
      of Ag+ by gallic acid by providing nucleation seeds. Ag+ was reduced to Ag
      degrees  and accumulated on the PVA-AgNP surface, leading to an increase in the
      size of particles. The absorbance of the colloidal solution was drastically
      enhanced with a small red shift. Under optimal conditions, a linear response was
      established between the change in absorbance and the TAC value expressed in terms
      of gallic acid equivalents. The linear range was from 25 to 200MUM with a
      detection limit of 22.1MUM. Satisfactory precision was obtained with % relative
      standard deviation (RSD) of 2.17. The developed sensor was successfully applied
      for TAC assessment of commercial ginger products. The PVA-AgNP sensor offers
      rapid analysis (within 5min) compared to other nanoparticle-based antioxidant
      assays. Synthesis of the particles and assay involved less-toxic chemicals, and
      is therefore a "greener" method.

PMID- 28501159
TI  - Depleting high-abundant and enriching low-abundant proteins in human serum: An
      evaluation of sample preparation methods using magnetic nanoparticle, chemical
      depletion and immunoaffinity techniques.
AB  - The efficiency of three different depletion methods to remove the most abundant
      proteins, enriching those human serum proteins with low abundance is checked to
      make more efficient the search and discovery of biomarkers. These methods utilize
      magnetic nanoparticles (MNPs), chemical reagents (sequential application of
      dithiothreitol and acetonitrile, DTT/ACN), and commercial apparatus based on
      immunoaffinity (ProteoMiner, PM). The comparison between methods shows
      significant removal of abundant protein, remaining in the supernatant at
      concentrations of 4.6+/-0.2, 3.6+/-0.1, and 3.3+/-0.2uguL-1 (n=3) for MNPs,
      DTT/ACN and PM respectively, from a total protein content of 54uguL-1. Using GeLC
      MS/MS analysis, MNPs depletion shows good efficiency in removing high molecular
      weight proteins (>80kDa). Due to the synergic effect between the reagents DTT and
      ACN, DTT/ACN-based depletion offers good performance in the depletion of thiol
      rich proteins, such as albumin and transferrin (DTT action), as well as of high
      molecular weight proteins (ACN action). Furthermore, PM equalization confirms its
      efficiency in concentrating low-abundant proteins, decreasing the dynamic range
      of protein levels in human serum. Direct comparison between the treatments
      reveals 72 proteins identified when using MNP depletion (43 of them exclusively
      by this method), but only 20 proteins using DTT/ACN (seven exclusively by this
      method). Additionally, after PM treatment 30 proteins were identified, seven
      exclusively by this method. Thus, MNPs and DTT/ACN depletion can be simple,
      quick, cheap, and robust alternatives for immunochemistry-based protein
      depletion, providing a potential strategy in the search for disease biomarkers.

PMID- 28501160
TI  - Bioaffinity-based assay for the sensitive detection and discrimination of sweat
      aimed at forensic applications.
AB  - Sweat is a well-known piece of biological evidence that is actually used much
      less than expected. Biological samples are important because their components can
      often provide some type of information about a person-of-interest. Sweat, in
      particular, is important because of its DNA content which can be extracted and
      analyzed to provide information that can be imperative to a criminal
      investigation. While it is a very important source of forensic information, the
      methods for detection and discrimination of sweat are limited, causing it to be
      overlooked during evidence collection. This manuscript presents a biocatalytic
      method for sweat detection that utilizes an enzyme cascade system that has the
      capability to detect trace amounts of sweat and distinguish it from saliva, even
      after the sample has dried. The results show the initial calibration studies
      performed to insure that the cascade performs well using both mimicked and
      authentic sweat samples which have components that could negatively affect the
      enzymes needed for the analysis. The method presented here also has the potential
      to be adapted for on-site analysis. The initial results of the development of a
      sweat-sensitive strip are shown here.

PMID- 28501162
TI  - Solidification of floating organic droplet in dispersive liquid-liquid
      microextraction as a green analytical tool.
AB  - Dispersive liquid-liquid microextraction (DLLME) is a special type of
      microextraction in which a mixture of two solvents (an extracting solvent and a
      disperser) is injected into the sample. The extraction solvent is then dispersed
      as fine droplets in the cloudy sample through manual or mechanical agitation.
      Hence, the sample is centrifuged to break the formed emulsion and the extracting
      solvent is manually separated. The organic solvents commonly used in DLLME are
      halogenated hydrocarbons that are highly toxic. These solvents are heavier than
      water, so they sink to the bottom of the centrifugation tube which makes the
      separation step difficult. By using solvents of low density, the organic
      extractant floats on the sample surface. If the selected solvent such as
      undecanol has a freezing point in the range 10-25 degrees C, the floating droplet
      can be solidified using a simple ice-bath, and then transferred out of the sample
      matrix; this step is known as solidification of floating organic droplet (SFOD).
      Coupling DLLME to SFOD combines the advantages of both approaches together. The
      DLLME-SFOD process is controlled by the same variables of conventional liquid
      liquid extraction. The organic solvents used as extractants in DLLME-SFOD must be
      immiscible with water, of lower density, low volatility, high partition
      coefficient and low melting and freezing points. The extraction efficiency of
      DLLME-SFOD is affected by types and volumes of organic extractant and disperser,
      salt addition, pH, temperature, stirring rate and extraction time. This review
      discusses the principle, optimization variables, advantages and disadvantages and
      some selected applications of DLLME-SFOD in water, food and biomedical analysis.

PMID- 28501161
TI  - Fabrication of selective chemical sensor with ternary ZnO/SnO2/Yb2O3
      nanoparticles.
AB  - Construction of highly efficient toxic chemical sensors is the key approach for
      the determination of carcinogenic chemicals in the environment and ecosystem. We
      report here, an efficient acetone chemical sensor based on the analytical
      performances such as sensitivity, lower-detection limit, reproducibility, and
      good linearity. The proposed acetone-detecting electrode was introduced by the
      implementation of ZnO/SnO2/Yb2O3 nanoparticles (NPs) as a successful electron
      mediator with glassy carbon electrode (GCE) assembly. The prepared NPs of
      ZnO/SnO2/Yb2O3 were well crystalline-doped nanomaterial and produced by
      implementation of hydrothermal procedure at low temperature. The conventional
      methods such as Fourier-transform infrared spectroscopy (FTIR), ultraviolet
      visible spectroscopy (UV/vis), field emission scanning electron microscopy
      (FESEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray
      spectroscopy (EDS), and powder x-ray diffraction (XRD) were utilized for
      characterization of prepared NPs in terms of morphological, elemental, optical
      and structural properties. The large linear dynamic range (LDR) of 0.34nmolL-1 to
      3.4mmolL-1 with lower detection limit (S/N=3) of 0.05+/-0.002nmolL-1 and a higher
      sensitivity of 17.09uAmmolL-1cm-2 were exhibited by lab-made fabricated sensor
      based on ZnO/SnO2/Yb2O3 NPs for selective acetone detection. In shortly, the
      ZnO/SnO2/Yb2O3 NPs are utilized as an excellent electron mediator with Nafion/GCE
      assembly in a chemical sensor for acetone detection even at the very low
      concentration. Therefore, the chemical sensor is fabricated with ZnO/SnO2/Yb2O3
      NPs may be a promising highly sensitive sensor by reliable I-V detection method
      for the effective detection of hazardous and carcinogenic chemicals in medical as
      well as health-care fields.

PMID- 28501163
TI  - On-line immunoaffinity solid-phase extraction capillary electrophoresis mass
      spectrometry using Fab'antibody fragments for the analysis of serum
      transthyretin.
AB  - This paper describes an on-line immunoaffinity solid-phase extraction capillary
      electrophoresis mass spectrometry (IA-SPE-CE-MS) method using an immunoaffinity
      sorbent with Fab' antibody fragments (Fab'-IA) for the analysis of serum
      transthyretin (TTR), a homotetrameric protein (Mr~56,000) involved in different
      types of amyloidosis. The IA sorbent was prepared by covalent attachment of Fab'
      fragments obtained from a polyclonal IgG antibody against TTR to succinimidyl
      silica particles. The Fab'-IA-SPE-CE-MS methodology was first established
      analyzing TTR standard solutions. Under optimized conditions, repeatability and
      reproducibility were acceptable, the method was linear between 1 and 25ugmL-1,
      limits of detection (LODs) were around 0.5ugmL-1 (50-fold lower than by CE-MS,
      ~25ugmL-1) and different TTR conformations were observed (folded and unfolded).
      The applicability of the developed method to screen for familial amyloidotic
      polyneuropathy type I (FAP-I), which is the most common hereditary systemic
      amyloidosis, was evaluated analyzing serum samples from healthy controls and FAP
      I patients. For the analysis of sera, the most abundant proteins were
      precipitated with 5% (v/v) of phenol before Fab'-IA-SPE-CE-MS. The current method
      enhanced our previous results for the analysis of TTR using intact antibodies
      immobilized on magnetic beads. It allowed a slight improvement on LODs (2-fold),
      the detection of proteoforms found at lower concentrations and the preparation of
      microcartridges with extended durability.

PMID- 28501164
TI  - A nanocluster-based fluorescent sensor for sensitive hemoglobin detection.
AB  - In this report, a fluorescence sensor for sensitive detection of hemoglobin was
      developed. Gold nanoclusters were first synthesized with bovine serum albumin. It
      was found that both hydrogen peroxide and hemoglobin could weakly quench the
      fluorescence from the gold nanoclusters, but when these two were applied onto the
      nanolcusters simultaneously, a much improved quenching was resulted. This
      enhancing effect was proved to come from the catalytic generation of hydroxyl
      radical by hemoglobin. Under an optimized condition, the quenching linearly
      related to the concentration of hemoglobin in the range of 1-250nM, and a limit
      of detection as low as 0.36nM could be obtained. This provided a sensitive means
      for the quantification of Hb. The sensor was then successfully applied for blood
      analyses with simple sample pretreatment.

PMID- 28501165
TI  - A portable somatic cell counter based on a multi-functional counting chamber and
      a miniaturized fluorescence microscope.
AB  - A somatic cell count is the concentration or density of somatic cells in milk,
      and is an important indicator for monitoring mastitis incidence and milk quality
      in the dairy industry. Managing and controlling mastitis based on somatic cell
      counts can help ensure high milk quality and yield. A major challenge when
      translating existing cell counting methods to such application is that they
      require off-chip sample preparation and complicated sample and reagent delivery
      steps that cannot be easily performed in resource-limited settings such as dairy
      farms. Here, we describe an integrated cell counting platform that enables
      automatic sample delivery into a cell counting chamber and on-chip sample
      preparation without requiring any off-chip processes, and that simultaneously
      provides a miniaturized, hand-held fluorescence device for the identification of
      fluorescently-labelled somatic cells. Our platform thus allows simple, rapid and
      accurate enumeration of somatic cells in milk. We successfully demonstrated its
      capability of counting somatic cells in milk, which can be easily performed even
      by non-experts without additional instrumentation. The platform represents a
      promising tool for everyday milk-quality tracking and for controlling mastitis
      occurrence.

PMID- 28501166
TI  - Synthesis and evaluation of a molecularly imprinted polymer for selective
      adsorption and quantification of Acid Green 16 textile dye in water samples.
AB  - An alternative for determining environmental pollutants, like textile dyes, is
      the use of molecularly imprinted polymers (MIPs) as solid phase extraction (SPE)
      or as sensor recognition systems. MIPs are tailor-made artificial receptor sites
      in a polymer, which present good affinity and selectivity. This work shows the
      synthesis of MIPs for the Acid Green 16 (AG16) textile dye and the results of
      rebinding, selectivity and application of this MIP in water samples. MIP
      synthesis was performed using AG16 dye (template), 1-vinylimidazole (functional
      monomer), ethylene-glycol-dimethacrylate (cross-link), 2,2'-azobis(2
      methylpropionitrile) (initiator) and methanol (solvent) by bulk synthesis. The
      imprinted polymer presented excellent rebinding of 83%, an imprinted factor of
      6.91 and great selectivity in comparison with other textile dyes. Additionally,
      the MIP showed high efficiency in the extraction of this dye in water samples,
      presenting a recovery rate close to 100% and a better performance when compared
      to commercial SPE cartridges. Due to this excellent performance for AG16, the
      application of this MIP to determine dyes in different matrices of environmental
      importance is promising.

PMID- 28501167
TI  - Polyoxometalate incorporated polymer monolith microextraction for highly
      selective extraction of antidepressants in undiluted urine.
AB  - In this work, a polyoxometalate (POM) incorporated polymer monolith
      microextraction (PMME) was successfully proposed and employed in the selective
      extraction of basic antidepressants in undiluted urine sample. This hybrid
      monolith exhibited strong cation-exchange interaction (SCX) with positively
      charged antidepressants when pH was 3.0, because of the multiple ionizable
      moieties on polyanionic POM. As such, antidepressants in complex sample matrices
      were efficiently extracted by the monolith, and the matrix effect was
      significantly reduced. In addition, due to the high amount of anionic POM, the
      monolith exhibited remarkable extraction capacities for target antidepressants
      ranging from 4.7 to 5.8mg/g. Further, the POM incorporated PMME was coupled with
      high-performance liquid chromatography-ultraviolet (HPLC-UV). Thus,
      antidepressants in undiluted urine sample was efficiently extracted under
      optimized extraction conditions online. The limits of detection (LODs) for the
      target antidepressants ranged from 0.7 to 1.4ng/mL, and the linear range was 5
      1000ng/mL with determination coefficients (R2) higher than 0.9960. The recoveries
      ranged from 86.8% to 104.0% with relative standard deviations (RSDs) of 0.4
      10.1%. The proposed procedure was successfully applied to determine
      antidepressant in human urine. Taken together, the developed method presented a
      new strategy for the analysis of basic drugs in undiluted urine sample, which
      could be used for monitoring medicines in pharmacokinetic analysis.

PMID- 28501168
TI  - High sensitivity thermal lens microscopy: Cr-VI trace detection in water.
AB  - In this work, a low detection limit for hexavalent chromium in water of parts per
      trillions (21ng/L) was achieved using a micro-spatial thermal lens spectroscopy
      setup with coaxial counter-propagating pump and probe laser beams and an
      integrated passive optical Fabry-Perot resonator, aided with a well-established
      diphenyl carbazide colorimetric method. Cr-VI concentrations in the range of
      MUg/L, i.e. well-below the toxicity thresholds in humans and animals (26 and
      190mg/L respectively) and below those delimited by international regulations for
      drink water (~0.05-0.5mg/L), have been obtained by measurements in bottled and
      tap water samples. The developed thermal lens microscope is also capable to
      detect Cr-VI directly in potassium dichromate solutions using pump beam
      wavelengths within the very low optical absorption region in the visible part of
      the spectrum, i.e., without the use of any colorimetric method.

PMID- 28501169
TI  - Aqueous biphasic systems containing PEG-based deep eutectic solvents for high
      performance partitioning of RNA.
AB  - In this work, 16 kinds of novel deep eutectic solvents (DESs) composed of
      polyethylene glycol (PEG) and quaternary ammonium salts, were coupled with
      Aqueous Biphasic Systems (ABSs) to extract RNA. The phase forming ability of ABSs
      were comprehensively evaluated, involving the effects of various proportions of
      DESs' components, carbon chain length and anions species of quaternary ammonium
      salts, average molecular weights of PEG and inorganic salts nature. Then the
      systems were applied in RNA extraction, and the results revealed that the
      extraction efficiency values were distinctly enhanced by relatively lower PEG
      content in DESs, smaller PEG molecular weights, longer carbon chain of quaternary
      ammonium salts and more hydrophobic inorganic salts. Then the systems composed of
      [TBAB][PEG600] and Na2SO4 were utilized in the influence factor experiments,
      proving that the electrostatic interaction was the dominant force for RNA
      extraction. Therefore, back-extraction efficiency values ranging between 85.19%
      and 90.78% were obtained by adjusting the ionic strength. Besides, the selective
      separation of RNA and tryptophane (Trp) was successfully accomplished. It was
      found that 86.19% RNA was distributed in the bottom phase, while 72.02% Trp was
      enriched in the top phase in the novel ABSs. Finally, dynamic light scattering
      (DLS) and transmission electron microscope (TEM) were used to further investigate
      the extraction mechanism. The proposed method reveals the outstanding feasibility
      of the newly developed ABSs formed by PEG-based DESs and inorganic salts for the
      green extraction of RNA.

PMID- 28501170
TI  - A star-shaped poly(2-methyl-2-oxazoline)-based antifouling coating: Application
      in investigation of the interaction between acetaminophen and bovine serum
      albumin by frontal analysis capillary electrophoresis.
AB  - In this work, an antifouling capillary modified with star-shaped poly(2-methyl-2
      oxazoline)-based copolymer was used to study the interaction between
      acetaminophen (APAP) and bovine serum albumin (BSA) by frontal analysis capillary
      electrophoresis (FACE). The star-shaped copolymer, poly(ethylene imine)-graft
      poly(2-methyl-2-oxazoline) (PEI-g-PMOXA), was immobilized onto the fused-silica
      capillary inner wall via dopamine-assisted co-deposition strategy, yielding a PEI
      g-PMOXA/polydopamine (PDA)-coated antifouling capillary, i.e., an antifouling
      capillary coated with the PEI-g-PMOXA/PDA co-deposited film. Electroosmotic flow
      (EOF) mobility of the PEI-g-PMOXA/PDA-coated capillary was almost zero in a wide
      pH range (3.0-10.0), while the EOF mobility of bare capillary was much larger and
      increased significantly with pH increasing. When the PEI-g-PMOXA/PDA-coated
      capillary was exploited to separate a protein mixture including cytochrome c,
      lysozyme, ribonuclease A and alpha-chymotrypsinogen A, the theoretical plate
      numbers were of five orders of magnitude which were about ten-fold higher over
      those obtained with bare capillary; in addition, the RSD values of migration time
      were mostly less than 0.7% (30 consecutive runs) which were much smaller than
      those of bare capillary (c.a. 5.7%). The protein-resistant PEI-g-PMOXA/PDA-coated
      capillary was then used to investigate the interaction between APAP and BSA by
      FACE, the binding constant and number of binding sites at 25 degrees C and pH 7.4
      (Tris/HCl buffer of 25mM) were 1.39*104M-1 and 1.08, respectively, which were
      comparable to the results determined by fluorescence spectroscopic measurement
      (3.18*104M-1 and 1.19, respectively).

PMID- 28501171
TI  - A novel magnetic/photoluminescence bifunctional nanohybrid for the determination
      of trypsin.
AB  - In this work, we have designed a novel kind of nanohybrid with magnetic and
      photoluminescence (PL) property for trypsin detection. The modified magnetic
      Fe3O4 nanoparticles (MNPs) with polydopamine (PDA) and human serum albumin (HSA)
      were prepared through a one step self-polymerization under mild condition. The
      polydopamine (PDA) coating on MNPs can improve the biocompatibility of the MNP
      PDA-HAS composite due to its hydrophilicity and multifunctional groups. When MNP
      PDA-HSA composite was added into the Anti-HSA modified CdTe QDs (anti-HSA-QDs),
      HSA on the MNP-PDA-HSA composite was captured by the site of anti-HSA-QDs to form
      MNP-PDA-HSA/anti-HSA-QDs nanohybrid. Therefore, the photoluminescence of QDs can
      be quenched by Fe3O4 nanoparticles due to the electron transfer. In the presence
      of trypsin, the protein (anti-HSA) was digested by trypsin and QDs was separated
      from the nanohybrid surface. As a result, the photoluminescence intensity of QDs
      was recovered. The magnetic/luminescent bifunctional nanohybrid displayed
      excellent analytical performance for the detection of trypsin in the range of 0.5
      30MUg/mL with a low detection limit of 0.25MUg/mL.

PMID- 28501172
TI  - Combining phagomagnetic separation with immunoassay for specific, fast and
      sensitive detection of Staphylococcus aureus.
AB  - A Staphylococcus aureus (S. aureus)-specific lytic bacteriophage P-S. aureus-9,
      isolated from an environmental water sample, was assembled on magnetic beads for
      capturing S. aureus from samples through magnetic separation. Horseradish
      Peroxidase (HRP) labeled immunoglobulin (IgG) antibodies were used to detect the
      captured S. aureus by reacting with protein A on S. aureus followed by
      colorimetric signals, which were generated from the catalytic reaction between
      HRP and the substrate 3,3',5,5'-Tetramethylbenzidine (TMB). Under optimal
      conditions, the calibration curve was linear from 1.0*104 to 1.0*106CFUmL-1. The
      limit of detection (LOD) for the assay was 2.47*103CFUmL-1 and 8.86*103CFUmL-1 of
      S. aureus in PBS and apple juice, respectively. Moreover, the whole assay
      revealed outstanding specificity towards S. aureus, without any interference of
      common pathogenic bacteria, and can be completed within 90min without any pre
      enrichment. As far as known, it was the first time to detect S. aureus based on
      the double site recognition of bacteriophage and mammal IgG. The novel approach
      has shown good potentials for a rapid, specific, cheap and simple detection of S.
      aureus in food samples.

PMID- 28501173
TI  - An exploiting of cost-effective direct current conductivity detector in gas
      diffusion flow injection system.
AB  - In this work, a homemade direct current (DC) conductivity detector as an
      alternative cost-effective detection device has been fabricated and investigated
      to use in flow analysis system. Under the selected appropriate conditions of flow
      system, the electrolysis of a carrier stream at the conductivity detector was
      negligible and provides well-defined signal. The cost-effective DC conductivity
      detector was demonstrated to couple with gas diffusion flow injection system for
      determination of dissolved inorganic carbon (DIC) in water. The method is based
      on the conversion of DIC (dissolved CO2, HCO3- and CO32-) presented in the
      injected sample to carbon dioxide in an acidic donor stream and then CO2 gas
      diffuses through a hydrophobic porous membrane to an acceptor stream. As a
      result, the change of conductivity signal was observed corresponding to DIC
      concentration. A linear calibration range of DIC in 1.0-10mmolL-1, with limit of
      detection of 70umolL-1, repeatability of <3% RSD and 15 injections h-1 sample
      throughput can be obtained. This method was applied for DIC determination in
      natural water.

PMID- 28501174
TI  - Polyhydric polymer-functionalized fluorescent probe with enhanced aqueous
      solubility and specific ion recognition: A test strips-based fluorimetric
      strategy for the rapid and visual detection of Fe3+ ions.
AB  - A polyhydric polymer-functionalized probe with enhanced aqueous solubility was
      designed initially by coupling 1-pyrenecarboxyaldehyde (Pyr) onto poly(vinyl
      alcohol) (PVA) via the one-step condensation reaction. Polyhydric PVA polymer
      chains could facilitate the Pyr fluorophore with largely improved aqueous
      solubility and especially strong cyan fluorescence. Importantly, the fluorescence
      of the PVA-Pyr probes could thereby be quenched specifically by Fe3+ ions through
      the strong PVA-Fe3+ interaction triggering the polymeric probe aggregation.
      Furthermore, a test strips-based fluorimetric method was developed with the
      stable and uniform probe distribution by taking advantage of the unique film
      forming ability and the depression capacity of "coffee-stain" effects of PVA
      matrix. The as-developed test strips could allow for the rapid and visual
      detections of Fe3+ ions simply by a dipping way, showing a linear concentration
      range of 5.00-300MUM, with the detection limit of 0.73MUM. Moreover, the proposed
      method was applied to the evaluation of Fe3+ ions in natural water samples,
      showing the analysis performances better or comparable to those of current
      detection techniques. This test strips-based fluorimetric strategy promises the
      extensive applications for the rapid on-site monitoring of Fe3+ ions in
      environmental water and the outdoor finding of the potential iron mines.

PMID- 28501175
TI  - Sensitive determination of endogenous hydroxyl radical in live cell by a BODIPY
      based fluorescent probe.
AB  - The sensitive and selective fluorescence probe for hydroxyl radical analysis is
      of significance because hydroxyl radical plays key roles in many physiological
      and pathological processes. In this work, a novel organic fluorescence molecular
      probe OHP for hydroxyl radical is synthesized by a two-step route. The probe
      employs 4-bora-3a,4a-diaza-s-indacene (difluoroboron dipyrromethene, BODIPY) as
      the fluorophore and possesses relatively high fluorescence quantum yields
      (77.14%). Hydroxyl radical can rapidly react with the probe and quench the
      fluorescence in a good linear relationship (R2=0.9967). The limit of detection is
      determined to be as low as 11nM. In addition, it has been demonstrated that the
      probe has a good stability against pH and light illumination, low cytotoxicity
      and high biocompatibility. Cell culture experimental results show that the probe
      OHP is sensitive and selective for imaging and tracking endogenous hydroxyl
      radical in live cells.

PMID- 28501176
TI  - Liquid chromatography-high resolution mass spectrometric methods for the
      surveillance monitoring of cyanotoxins in freshwaters.
AB  - A comprehensive risk management on human exposure to cyanotoxins, whose
      production is actually unpredictable, is limited by reliable analytical tools for
      monitoring as many toxic algal metabolites as possible. Two analytical approaches
      based on a LC-QTOF system for target analysis and suspect screening of
      cyanotoxins in freshwater were presented. A database with 369 compounds belonging
      to cyanobacterial metabolites was developed and used for a retrospective data
      analysis based on high resolution mass spectrometry (HRMS). HRMS fragmentation of
      the suspect cyanotoxin precursor ions was subsequently performed for correctly
      identifying the specific variants. Alternatively, an automatic tandem HRMS
      analysis tailored for cyanotoxins was performed in a single chromatographic run,
      using the developed database as a preferred precursor ions list. Twenty-five
      extracts of surface and drinking waters contaminated by cyanobacteria were
      processed. The identification of seven uncommon microcystins (M(O)R, MC-FR, MSer7
      YR, D-Asp3MSer7-LR, MSer7-LR, dmAdda-LR and dmAdda-YR) and 6 anabaenopeptins (A,
      B, F, MM850, MM864, oscyllamide Y) was reported. Several isobaric variants, fully
      separated by chromatography, were pointed out. The developed methods are proposed
      to be used by environmental and health agencies for strengthening the
      surveillance monitoring of cyanotoxins in water.

PMID- 28501177
TI  - Determination of stability characteristics for electrochemical biosensors via
      thermally accelerated ageing.
AB  - Biosensors are devices that are prone to ageing; this phenomenon can be
      characterized as a decrease in signal over time. Biosensor stability is of a
      crucial importance for commercial success and as biosensors are presently being
      applied to an increasing and variety of applications. Stability characteristics
      related to shelf life, reusability and/or continuous use stability are often
      poorly investigated or unreported in literature, yet are important factors.
      Instability or ageing can be accelerated at an elevated temperature; Arrhenius
      (exponential) and linear models were investigated in order to propose a novel
      method for rapid ageing characteristics determination. Linear correlation proved
      more suitable with higher coefficients of determination than exponential
      correlation. Degradation rate is linearly dependent on temperature and by
      utilizing the proposed models, long term shelf life of a biosensor can be
      determined in 4 days and continuous use stability in less than 24h. Reusability
      studies are found to correlate poorly due to the unpredictable nature of
      biosensor handling. Basic constructed screen printed electrode glucose oxidase
      biosensors were used as a model biosensor in order to propose models for shelf
      life, reusability and continuous use stability.

PMID- 28501178
TI  - Electrochemically deposited conductive composite sorbent for highly efficient
      online solid-phase microextraction of jasmonates in plant samples.
AB  - Conductive composite films composed of poly (3, 4-ethylenedioxythiophene) (PEDOT)
      and sulfonated graphene were electrochemically deposited on carbon fiber bundle
      in aqueous solutions for solid phase microextraction (SPME). During the electro
      polymerization process, negatively charged sulfonated graphene were doped in
      PEDOT layer and uniformly dispersed in the composite. The modified carbon fiber
      bundle worked as sorbent was then successfully applied to online SPME-HPLC-UV
      analysis of jasmonates in wintersweet flowers. High extraction efficiency (over
      420-fold), low limits of detection (0.1ngmL-1 for jasmonic acid and 0.01ngmL-1
      for methyl jasmonate) and wide linear ranges (0.5-5000 and 0.05-5000ngmL-1,
      R>0.9997) have been obtained. It has been demonstrated that this method can be
      well used for jasmonates analysis in fresh wintersweet flowers with good
      recoveries (92.4-98.9%). The results were confirmed by HPLC-MS method.

PMID- 28501179
TI  - Determination of veterinary penicillin antibiotics by fast high-resolution liquid
      chromatography and luminescence detection.
AB  - A chromatographic method based on the use of a fused-core column and luminescence
      detection is described for the determination of six penicillin antibiotics used
      in veterinary practice, namely amoxicillin, ampicillin, penicillin G, oxacillin,
      cloxacillin and nafcillin. The use of this column provides the separation of
      these antibiotics with retention times lower than 4.5min. The tris(2,2'
      bipyridyl)ruthenium(II) [Ru(bpy)32+] - Ce(IV) system has been used as post-column
      derivatization reagent, obtaining a luminescence signal (lambdaem 610nm)
      proportional to the analyte concentration when the system is excited at 450nm.
      The dynamic ranges of the calibration graphs are 100-10,000ngmL-1 for all the
      antibiotics assayed and the limits of detection are in the range of 44-51ngmL-1.
      The precision, established at two concentration levels of each analyte and
      expressed as the percentage of the relative standard deviation is in the range of
      6.9-9.8%. The method has been satisfactorily applied to the analysis of water and
      pharmaceutical samples, with recoveries ranging from 88.6% to 108.5%.

PMID- 28501181
TI  - A voltammetry sensor platform for baicalein and baicalin simultaneous detection
      in vivo based on Ta2O5-Nb2O5@CTS composite.
AB  - Baicalein and baicalin are the major flavonoids found in Scutellariae Radix, an
      essential herb which has had a presence in traditional Chinese medicine (TCMs)
      for more than two thousands of years. Owing to their similar characteristics and
      physiochemical properties, sensitive, it is a great challenge to detect both of
      them simultaneously. In this work, a novel, facile and sensitive electrochemical
      method was proposed based on tantalum oxide (Ta2O5), niobium oxide (Nb2O5)
      particles and antiseptic chitosan modified carbon paste electrode (Ta2O5
      Nb2O5@CTS-CPE). Scanning electron microscope (SEM), X-ray diffraction
      spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), cyclic
      voltammetry (CV) and electrochemical impedance spectrum (EIS) were used to
      characterize the properties and investigate the electrochemical response of the
      sensor. The electrochemical behaviors and redox mechanisms of two analytes were
      investigated at the target electrode. Under the optimum conditions, the highly
      sensitive and simultaneous determination of baicalein and baicalin was
      successfully achieved with a linear response range of 0.08-8.0MUM for both of
      them. The obtained detection limits for baicalein and baicalin were of 0.05 and
      0.03MUM (S/N=3), respectively. Furthermore, the proposed sensor displayed high
      sensitivity, excellent stability and satisfactory results in Scutellariae Radix
      samples analysis and hydrolysis process analysis of baicalin in vivo.

PMID- 28501180
TI  - Detection of Abeta oligomers based on magnetic-field-assisted separation of
      aptamer-functionalized Fe3O4 magnetic nanoparticles and BaYF5:Yb,Er nanoparticles
      as upconversion fluorescence labels.
AB  - A sensitive and stable bioassay for the detection of Abeta oligomer (Abetao), a
      potentially promising candidate biomarker for Alzheimer's disease (AD) diagnosis,
      was developed using Fe3O4 magnetic nanoparticles (MNPs) as the recognition and
      concentration elements and BaYF5:Yb,Er upconversion nanoparticles (UCNPs) as
      highly sensitive labels, conjugated with the Abetao aptamer (DNA1) and the
      complementary oligonucleotide of the Abetao aptamer (DNA2), respectively. The
      DNA1 hybridized with DNA2 to form the duplex structure on the surface of the
      MNPs/UCNPs nanocomposites probe. When the target Abetao was introduced, the
      aptamer DNA1 preferentially bound with Abetao and caused the dissociation of some
      complementary DNA2, liberating some UCNP-labeled complementary DNA2 and leading
      to a decreased upconversion fluorescent intensity on the surface of MNPs. The
      decreased fluorescence intensity of UCNPs was related to the concentration of
      Abetao in the range of 0.2-15nM with a detection limit of 36 pM. The developed
      method then was successfully applied to measure Abetao in artificial
      cerebrospinal fluid. Benefiting from the magnetic separation and concentration
      effect of MNPs, the high sensitivity of UCNPs, as well as the selectivity and
      stability of the aptamer, the present strategy offered valuable information
      related to early diagnosis of AD process.

PMID- 28501182
TI  - Determination of Escherichia coli in urine using a low-cost foil-based
      microfluidic device.
AB  - We developed a simple low-cost cultivation-based microfluidic device from office
      laminator foil and Parafilm for the determination of specific microorganisms in
      water samples. The main goal was to obtain a device that would be portable and
      cheap compared to common laboratory techniques testing microorganisms. This
      device needs only 10uL of a sample and can be easily used in terrain by a non
      specialist. Moreover, we dealt with some technical aspects of the device
      fabrication such as low-cost lamination techniques and the use of different
      cultivation media.

PMID- 28501183
TI  - In-line moisture monitoring in fluidized bed granulation using a novel multi
      resonance microwave sensor.
AB  - Microwave resonance technology (MRT) is known as a process analytical technology
      (PAT) tool for moisture measurements in fluid-bed granulation. It offers a great
      potential for wet granulation processes even where the suitability of near
      infrared (NIR) spectroscopy is limited, e.g. colored granules, large variations
      in bulk density. However, previous sensor systems operating around a single
      resonance frequency showed limitations above approx. 7.5% granule moisture. This
      paper describes the application of a novel sensor working with four resonance
      frequencies. In-line data of all four resonance frequencies were collected and
      further processed. Based on calculation of density-independent microwave moisture
      values multiple linear regression (MLR) models using Karl-Fischer titration (KF)
      as well as loss on drying (LOD) as reference methods were build. Rapid, reliable
      in-process moisture control (RMSEP<=0.5%) even at higher moisture contents was
      achieved.

PMID- 28501184
TI  - Heavy metal contents of play dough, face and finger paint samples sold in turkish
      markets.
AB  - Lead, cadmium, nickel, manganese, cobalt and copper contents of some play dough,
      face and finger paint samples were determined by using a new solid phase
      extraction method which has been developed by using multi-walled carbon nanotube
      with patent blue (V) sodium salt to selectively separate and preconcentrate these
      metal ions. Flame atomic absorption spectrometry was used to determine the metal
      ions. Analytical parameters affecting the complex formation and solid phase
      extraction performance such as pH, the amount of ligand and volume of sample
      solution were investigated. The recoveries of the studied metal ions were not
      affected by the foreign ions. Analytes were recovered quantitatively at pH 5.5
      and with a nitric acid of 2molL-1 as eluent. Analysis of a certified reference
      material was performed to validate the method before applying it to determine the
      metal ions in the real samples. Detection limits were found to be as Pb(II):
      7.71MUgL-1, Cu(II): 1.43MUgL-1, Cd(III): 0.21MUgL-1, Mn(II): 0.47MUgL-1, Ni(II):
      3.52MUgL-1and Co(II): 1.96MUgL-1.

PMID- 28501185
TI  - Simultaneous voltammetric determination of vanillin and caffeine in food products
      using an anodically pretreated boron-doped diamond electrode: Its comparison with
      HPLC-DAD.
AB  - This paper describes an electroanalytical method for the simultaneous
      determination of vanillin (VAN) and caffeine (CAF) using an anodically pretreated
      boron-doped diamond electrode. Selective determination of one compound in the
      presence of other one was also realized. Both compounds yielded a single
      irreversible oxidation peak using cyclic voltammetry. The nature of the electrode
      reaction was found to be diffusion controlled with contribution of adsorption. By
      using square-wave adsorptive stripping voltammetry after 60s accumulation under
      open-circuit voltage, method allowed simultaneous determination of VAN and CAF in
      phosphate buffer, pH 2.5, with detection limits of 0.234ugmL-1 (1.54*10-6M) and
      0.071ugmL-1 (3.66*10-7M), respectively. The proposed method was successfully
      applied in the selective and simultaneous determination of VAN and CAF in
      commercial food and beverage samples. In addition, for the comparison, high
      performance liquid chromatographic method with diode-array detection was
      developed for the first time for their simultaneous determination.

PMID- 28501186
TI  - Application of Box-Behnken design to optimize multi-sorbent solid phase
      extraction for trace neonicotinoids in water containing high level of matrix
      substances.
AB  - Extensive use of neonicotinoid insecticides has raised great concerns about their
      ecological risk. A reliable method to measure trace neonicotinoids in complicated
      aquatic environment is a premise for assessing their aquatic risk. To effectively
      remove matrix interfering substances from field water samples before instrumental
      analysis with HPLC/MS/MS, a multi-sorbent solid phase extraction method was
      developed using Box-Behnken design. The optimized method employed 200mg HLB/GCB
      (w/w, 8/2) as the sorbents and 6mL of 20% acetone in acetonitrile as the elution
      solution. The method was applied for measuring neonicotinoids in water at a wide
      range of concentrations (0.03-100MUg/L) containing various amounts of matrix
      components. The recoveries of acetamiprid, imidacloprid, thiacloprid and
      thiamethoxam from the spiked samples ranged from 76.3% to 107% while clothianidin
      and dinotefuran had relatively lower recoveries. The recoveries of neonicotinoids
      in water with various amounts of matrix interfering substances were comparable
      and the matrix removal rates were approximately 50%. The method was sensitive
      with method detection limits in the range of 1.8-6.8ng/L for all target
      neonicotinoids. Finally, the developed method was validated by measurement of
      trace neonicotinoids in natural water.

PMID- 28501187
TI  - Voltammetric determination of reduced glutathione using poly(thionine) as a
      mediator in the presence of Fenton-type reaction.
AB  - An indirect and sensitive electrochemical method for the determination of reduced
      glutathione (GSH) was developed by using poly(thionine) (PTH) as a mediator in
      the presence of Fenton-type reaction on the electrode surface in this work.
      Cyclic voltammetry and the adsorption of Cu2+ were employed in sequence to
      fabricate a Cu-PTH modified electrode, which was characterized by scanning
      electron microscopy, XPS and electrochemical measurements. Hydroxyl radicals that
      were derived from the Fenton-type reaction between Cu2+ and H2O2 could
      effectively oxidize PTH, leading to the great enhancement of the cathodic peak
      current of the dye polymer in the cyclic voltammetric scan. The electroreduction
      of PTH on the electrode surface was found to be inhibited in the presence of GSH.
      Under the optimized conditions, the cathodic peak current change was found to be
      proportional to the logarithm of the GSH concentration from 10nM to 1mM with a
      detection limit of 2.5nM estimated at a signal-to-noise ratio of 3. The proposed
      electrochemical sensor was successfully employed for the determination of GSH in
      real samples with satisfactory results.

PMID- 28501188
TI  - A hemicyanine-based colorimetric and ratiometric fluorescent probe for selective
      detection of cysteine and bioimaging in living cell.
AB  - A new ratiometric fluorescent probe based on a hemicyanine dye was synthesized.
      Investigation on the response behavior towards amino acids showed that the probe
      had a capability of rapidly and selectively detecting cysteine over other
      biothiols such as glutathione and homocysteine with similar structure and
      reactivity, and it also displayed a high selectivity and rapid response.
      Moreover, the probe had good water solubility, which authorized it could be
      applied in fluorescent bioimaging. The laser confocal fluorescence images
      indicated that the probe could visualize the intracellular cysteine. This work
      suggested that it could be utilized as a fluorescent indicator to discriminate
      the endogenous cysteine in living cells.

PMID- 28501189
TI  - High selective potentiometric sensor for determination of nanomolar con
      centration of Cu(II) using a polymeric electrode modified by a graphene/7,7,8,8
      tetracyanoquinodimethane nanoparticles.
AB  - In this paper we present several possibilities for modification of the all-solid
      state copper(II)-selective electrodes in order to obtain high stability and
      selectivity potentiometric sensor signal. The copper(II)-selective electrodes
      were modified in a simple way by introducing solid contact layer based on
      graphene or graphene oxide, 7,7,8,8-tetracyanoquinodimethane or its copper salt.
      Each of electrodes shown a Nernstian response, wide linear range of Cu2+
      concentration and a low detection limit. Nevertheless, some differences between
      the groups of electrodes have been noticed and resulted from application of
      intermediate layers of various compositions. The electrode modified with graphene
      and 7,7,8,8-tetracyanoquinodimethane nanocomposite exhibited the best potential
      reproducibility and detection limit. Moreover, prepared sensors were
      characterized by an improved selectivity for copper(II) in relation to non
      modified electrodes. The developed electrodes were successfully used for the Cu2+
      determination in different samples and results were comparable with those
      obtained using voltammetry.

PMID- 28501190
TI  - HPLC-UV and HPLC-CAD chromatographic data fusion for the authentication of the
      geographical origin of palm oil.
AB  - Data fusion combined with a multivariate classification approach (partial least
      squares-discriminant analysis, PLS-DA) was applied to authenticate the
      geographical origin of palm oil. Data fusion takes advantage of the synergistic
      effect of information collected from more than one data source. In this study,
      data from liquid chromatography coupled to two detectors -ultraviolet (UV) and
      charged aerosol (CAD)- was fused by high- and mid-level data fusion strategies.
      Mid-level data fusion combines a few variables from each technique and then
      applies the classification technique. Principal component analysis and interval
      partial least squares were applied to obtain the variables selected. High-level
      data fusion combines the PLS-DA classification results obtained individually from
      the chromatographic technique with each detector. Fuzzy aggregation connective
      operators were used to make the combinations. Prediction rates varied between 73%
      and 98% for the individual techniques and between 87% and 100% and 93% and 100%
      for the mid- and high-level data fusion strategies, respectively.

PMID- 28501191
TI  - TLC-UV hyphenated with MALDI-TOFMS for the screening of invertase substrates in
      plant extracts.
AB  - In this study, thin-layer chromatography (TLC) hyphenated with matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was
      developed for the screening of invertase substrates in complex matrices. BfrA, a
      specific beta-D-fructofuranosidase from Leishmania major, was chosen as a model
      enzyme to screen biological activity in plant extracts due to its capacity to
      hydrolyze specific carbohydrates. TLC was considered to be a reliable technique
      for screening substrates (bioactive molecules) in plant extracts due to its
      quantitative capabilities whereas MALDI-TOFMS was particularly useful for rapid
      identification. The first part of this approach consisted of a differential
      analysis by TLC-densitometry to highlight band under- and over-expressions in
      plant extract between blank and enzymatic reaction. Zones of interest were then
      immediately analyzed by TLC-MALDI-TOFMS coupling to identify bioactive molecules.
      Development of the method presented various challenges: the separation and
      analysis of isomers (such as glucose and fructose), the high matrix effect
      (demonstrated by the analysis of products with invertase enzyme naturally present
      in plant extract), and the analysis of polar molecules with low molecular mass
      (sugars). Thanks to the separative technique, the specificity of detection, and
      the high precision of the characterization, this method was shown to be feasible
      for the analysis of bioactive molecules in complex mixtures containing
      interfering compounds (e.g. proteins, salts). Overall, this study demonstrates
      that Thin-layer chromatography hyphenated with Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry is a simple, rapid,
      precise and efficient method for the analysis of suitable substrates in raw
      samples.

PMID- 28501192
TI  - Variability of fluorescence spectra of coelenteramide-containing proteins as a
      basis for toxicity monitoring.
AB  - Nowadays, physicochemical approach to understanding toxic effects remains
      underdeveloped. A proper development of such mode would be concerned with
      simplest bioassay systems. Coelenteramide-Containing Fluorescent Proteins (CLM
      CFPs) can serve as proper tools for study primary physicochemical processes in
      organisms under external exposures. CLM-CFPs are products of bioluminescent
      reactions of marine coelenterates. As opposed to Green Fluorescent Proteins, the
      CLM-CFPs are not widely applied in biomedical research, and their potential as
      colored biomarkers is undervalued now. Coelenteramide, fluorophore of CLM-CFPs,
      is a photochemically active molecule; it acts as a proton donor in its electron
      excited states, generating several forms of different fluorescent state energy
      and, hence, different fluorescence color, from violet to green. Contributions of
      the forms to the visible fluorescence depend on the coelenteramide
      microenvironment in proteins. Hence, CLM-CFPs can serve as fluorescence
      biomarkers with color differentiation to monitor results of destructive
      biomolecule exposures. The paper reviews experimental and theoretical studies of
      spectral-luminescent and photochemical properties of CLM-CFPs, as well as their
      variation under different exposures - chemicals, temperature, and ionizing
      radiation. Application of CLM-CFPs as toxicity bioassays of a new type is
      justified.

PMID- 28501193
TI  - Immunoaffinity chromatography combined with tandem mass spectrometry: A new tool
      for the selective capture and analysis of brassinosteroid plant hormones.
AB  - Brassinosteroids (BRs) are plant-specific steroid hormones that play essential
      roles in the regulation of many important physiological processes in plant life.
      Their extremely low concentrations (~pmoles/g FW) in plant tissue and huge
      differences in polarity of individual members within the BR family hamper their
      detection and quantification. To address this problem, an immunoaffinity sorbent
      with broad specificity and high capacity for different BR metabolites containing
      a monoclonal antibody (mAb) against a BR spacer (20S)-2alpha,3alpha-dihydroxy-7
      oxa-7alpha-homo-5alpha-pregnane-6-one-20 carboxylic acid (BR4812) was used for
      the rapid and highly selective isolation of endogenous BRs containing a
      2alpha,3alpha-diol in ring A from minute plant samples. This enrichment procedure
      was successfully applied as a sample preparation method prior to quantitative
      analysis of BRs in real plant tissues by ultra-high performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS). Use of immunoaffinity
      chromatography (IAC) increased the sensitivity of the UHPLC-MS/MS analysis owing
      to improvements in the BR signal-to-noise ratio (S/N) and matrix factor (MF).
      Although MF values of BRs analyzed in classical samples ranged from 8.9% to
      47.4%, MF values for the IAC purified samples reached 44.5-96.6%. Thus, the
      developed IAC-UHPLC-MS/MS approach was shown to be a simple, robust, effective
      and extremely fast procedure requiring minute amounts of plant samples suitable
      for the quantitative profiling of many BR metabolites, helping to overcome the
      major problems associated with their determination in very complex plant
      matrices.

PMID- 28501194
TI  - The use of Stationary Phase Optimized Selectivity Liquid Chromatography for the
      development of herbal fingerprints to detect targeted plants in plant food
      supplements.
AB  - The consumption of plant food supplements is increasing steadily and more and
      more, these products are bought through internet. Often the products sold through
      internet are not registered or declared with a national authority, meaning that
      no or minimal quality control is performed and that they could contain herbs or
      plants that are regulated. Stationary Phase Optimized Selectivity Liquid
      Chromatography (SOS-LC) was evaluated for the development of specific
      fingerprints, to be used for the detection of targeted plants in plant food
      supplements. Three commonly used plants in plant food supplements and two
      regulated plants were used to develop fingerprints with SOS-LC. It was shown that
      for all plants specific fingerprints could be obtained, allowing the detection of
      these targeted plants in triturations with different herbal matrices as well as
      in real samples of suspicious supplements seized by the authorities. For three of
      the five plants a more specific fingerprint was obtained, compared to the ones
      developed on traditional columns described in literature. It could therefore be
      concluded that the combination of segments of different types of stationary
      phases, as used in SOS-LC, has the potential of becoming a valuable tool in the
      quality control and the identification of crude herbal or plant material and in
      the detection of regulated plants in plant food supplements or other herbal
      preparations.

PMID- 28501195
TI  - Recycling polymer residues to synthesize magnetic nanocomposites for dispersive
      micro-solid phase extraction.
AB  - The ubiquitous presence of plastics, an obvious consequence of their usefulness
      and low price, has turned them into a problem of environmental and safety
      concern. The new plastic economy, an initiative recently launched by the World
      Economic Forum and Ellen MacArthur Foundation, with analytical support from
      McKinsey & Company, promotes a change in the use of plastic worldwide around
      three main pillars: redesign, reusing and recycling. Recycled plastics, with the
      aim of extending their life spam, can be used to synthesize materials for
      analytical purposes. In this article polystyrene (PS) trays, previously used for
      food packaging, are proposed as polymeric source for the synthesis of magnetic
      nanocomposites. The synthesis plays with the solubility of PS in different
      solvents in such a way that PS is gelated in the presence of cobalt ferrite
      nanoparticles which are finally embedded in the polymeric network. The extraction
      capability of the magnetic PS nanocomposite was evaluated using the determination
      of four parabens (methylparaben, ethylparaben, propylparaben and butylparaben) in
      water using liquid chromatography-tandem mass spectrometry as model analytical
      problem. Under the optimum conditions, limits of detection and quantification
      were in the range of 0.05-0.15 and 0.15-0.5ng/mL, respectively. The precisions,
      expressed as relative standard deviation (RSD), varied between 4.4% and 8.5% and
      the relative recoveries for analysis of the water samples were in the interval
      81.2-104.5%.

PMID- 28501196
TI  - Calibration transfer between different analytical methods.
AB  - The procedure for transfer of calibration models between different analytical
      methods is suggested. It is based on the direct standardization (DS) algorithm
      earlier suggested for data conversion between physically different instruments of
      the same type. As a result, multivariate regression models obtained e.g. for NIR
      spectroscopic measurements in one wavelength range can be successfully applied
      for predictions from the data obtained with another NIR spectrometer in another
      wavelength range. The performance of the suggested method was tested with two
      simulated and two real datasets. In the latter case calibration models
      constructed for energy-dispersive X-ray fluorescence, UV-Vis spectrometry and NIR
      spectrometry were addressed. The observed performance of the method implies that
      it can have a broad range of possible applications in analytical chemistry; some
      of them are suggested in the paper.

PMID- 28501197
TI  - Methylmercury determination in seafood by photochemical vapor generation
      capacitively coupled plasma microtorch optical emission spectrometry.
AB  - A non-chromatographic method based on double liquid-liquid extraction and
      measurements by UV photochemical vapor generation capacitively coupled plasma
      microtorch optical emission spectrometry was developed and characterized for
      methylmercury determination in seafood. Samples were prepared following the
      procedure recommended in JRC Technical Report of European Commission formerly
      proposed for the determination of methylmercury in seafood by thermal
      decomposition atomic absorption spectrometry, namely confinement of Hg species in
      47% HBr solution, extraction of CH3Hg+ in toluene and back-extraction in 1% l
      cysteine aqueous solution. Mercury cold vapor was generated by flow injection UV
      photo-reduction from CH3Hg+ in 0.6molL-1 HCOOH, while quantification was
      performed against external Hg2+ aqueous standards and measuring Hg 253.652nm
      emission using a low power/Ar consumption plasma microtorch (15W, 100mLmin-1) and
      a low resolution microspectrometer (Ocean Optics). The figures of merit and
      analytical capability were assessed by analyzing certified reference materials
      and test samples of fish fillet and discussed in relation with requirements for
      Hg determination in seafood in European legislation (Decisions 2007/333/EC and
      2002/657/EC) as well as compared to performances achieved in thermal
      decomposition atomic absorption spectrometry. The limit of detection and
      quantification of 2ugkg-1 and 6ugkg-1 respectively, precision of 2.7-9.4% and
      accuracy of 99+/-8% of the proposed method for the determination of CH3Hg+
      fulfill the demands of European legislation for Hg quantification. The limit of
      detection and quantification were better than those in the used reference method
      or other non-/chromatographic methods taken for comparison. The analysis of
      certified reference materials and the Bland and Altman test performed on 12 test
      samples confirmed trueness of the proposed method and its reliability for the
      determination of traces of CH3Hg+ with 95% confidence level. The proposed method
      fulfills several demands of the eco-scale concept, is sensitive, simple and safe
      related to sample preparation through elimination of classical, harmful
      reductants and attractive by using economical miniaturized instrumentation
      incorporating a low power and low Ar consumption plasma.

PMID- 28501198
TI  - Introducing plasma/serum glycodepletion for the targeted proteomics analysis of
      cytolysis biomarkers.
AB  - A major class of clinical biomarkers is constituted of intracellular proteins
      which are leaking into the blood following ischemia, exposure to toxic
      xenobiotics or mechanical aggression. Their ectopic presence in plasma/serum is
      an indicator of tissue damage and raises a warning signal. These proteins,
      referred to as cytolysis biomarkers, are generally of cytoplasmic origin and as
      such, are devoid of glycosylation. In contrast, most plasma/serum proteins
      originate from the hepatic secretory pathway and are heavily glycosylated (at the
      exception of albumin). Recent advances in targeted proteomics have supported the
      parallelized evaluation of new blood biomarkers. However, these analytical
      methods must be combined with prefractionation strategies that reduce the
      complexity of plasma/serum matrix. In this article, we present the glycodepletion
      method, which reverses the hydrazide-based glycocapture concept to remove
      plasma/serum glycoproteins from plasma/serum matrix and facilitates the detection
      of cytolysis biomarkers. Glycodepletion was integrated to a targeted proteomics
      pipeline to evaluate 4 liver cytolysis biomarker candidates in the context of
      acetaminophen-induced acute hepatitis.

PMID- 28501199
TI  - Developing a sensor layer for the optical detection of amines during food
      spoilage.
AB  - A colourimetric sensor layer has been developed for ammonia and biogenic amines.
      Amine exposure induces a traffic light colour change from green to red.
      Recognition is performed by a pH indicator dye, covalently immobilised onto
      cellulose microparticles. The sensor microparticles are embedded into food-grade
      silicone. Selectivity of the pH indicator dye towards gaseous amine is obtained
      by complete embedding of the sensor particles within the ion-impermeable
      silicone. A response time of 1.5h has been achieved, with a reverse response
      occurring after 20h. This time frame is considered sufficient for spoilage
      processes. Cytotoxicity studies confirm the layers are non-toxic.

PMID- 28501200
TI  - A new approach to calibration and determination of selected trace elements in
      food contact polymers by LA-ICP-MS.
AB  - A calibration strategy using porous nylon disks and reference solutions is
      proposed for the first time for matrix matching and determination of As, Ba, Cd,
      Cr, Pb, Sr and Zn in polymers by laser ablation-inductively coupled plasma mass
      spectrometry (LA-ICP-MS). Polymer samples commonly used in contact with food were
      analyzed. The procedure consists on the use of porous nylon disks as support for
      a dried droplet reference solution. Calibration in the range of 0.50-190MUgg-1
      for Ba, Cd, Cr, Pb, Sr and Zn and from 0.30-9.0MUgg-1 for As was used. Laser and
      ICP-MS instrument conditions were evaluated in order to achieve the best signal
      to-background ratio. The radiofrequency power and carrier gas flow rate were
      fixed at 1300W and 1.25Lmin-1, respectively. Spot size, repetition rate, scan
      line speed and laser fluency were set to 100um, 20Hz, 100ums-1 and 17.9Jcm-2,
      respectively, as the established conditions for analysis of standards and
      samples. By using these conditions, limits of detection, estimated considering
      B+3s (where B is the value of the blank and s is the standard deviation of 10
      measurements of the blank), ranged from 0.09MUgg-1 (208Pb) to 1.09 (53Cr) and
      0.05MUgg-1 (208Pb) to 2.10 (53Cr) for calibration with and without 13C as
      internal standard (IS). In spite to the use of nylon for matrix matching of
      different polymeric matrices, the normalization with 13C as IS was also
      evaluated. The precision of the method is relatively good (RSD<20%), and the
      accuracy of the method, evaluated by analysis of certified reference materials
      (CRM) and by comparison with results obtained from solution analysis by ICP-MS
      after sample decomposition by microwave induced combustion (MIC) is relatively
      good. The suitability of the proposed method resulted in direct and reliable
      analyses of polymer samples with a simplified or unnecessary sample preparation
      step. In addition, the calibration with dried droplet reference solutions may be
      considered a promising procedure in view of its advantages to other forms of
      calibration, as the use of CRM or the preparation of synthetic standards. The use
      of porous nylon disks spiked with reference solutions for calibration is the main
      advantage of the present work.

PMID- 28501201
TI  - Waste derivitized blue luminescent carbon quantum dots for selenite sensing in
      water.
AB  - Herein, we report an environmental friendly, facile, and completely green
      synthetic method for producing carbon quantum dots (CQDs) from whey, a major
      dairy waste. The as-prepared monodispersed diameter CQDs exhibit blue
      luminescence with noteworthy quantum yield (~11.4%) and excitation dependent
      emission behaviour. Nuclear magnetic resonance (NMR) analysis reveals the
      presence of aromatized carbon peaks, leading to polymerized CQDs diameter
      architecture during whey pyrolysis. The X-ray and selected area electron
      diffraction patterns confirm their amorphous nature. Further, we demonstrate,
      these CQDs as an effective sensor probe for selective selenite monitoring in
      water upon functionalization with appropriate ligand. The functionalized GCQDs
      probe is shown to detect selenite with high sensitivity in 10-1000ppb detection
      range. Further it is selective for selenite over other relevant ions (such as
      Cu2+, As3+, As5+, Pb2+, Ni2+, Se6+, Cl-, Br-, NO3-, NO2- and F-) and displays a
      sub-ppb detection limit at 1.1% relative standard deviation.

PMID- 28501202
TI  - A ratiometric fluorescent probe for hypochlorous acid determination: Excitation
      and the dual-emission wavelengths at NIR region.
AB  - An interesting ratiometric fluorescent probe with unique optical performance was
      reported in this work. By modifying on the bridge-head of heptamethine cyanine
      chromophore with an N-phenyl-N'-ethylene amine thiourea substituent as a
      chemodosimetric recognition unit, the probe exhibited ratiometric fluorescent
      response towards hypochlorous acid (HClO). Upon addition of HClO, the absorbance
      spectra showed a great red shift as large as 150nm from 650nm to 800nm. Employing
      the isosbestic absorption point at 730nm as an excitation wavelength, a
      ratiometric fluorescent sensing mode with two long emission wavelengths at 760nm
      and 820nm was acquired, and thus the probe displayed significant behavior with
      both the excitation wavelength and the dual-emission wavelengths located at NIR
      (650-900nm) region exclusively. Also, the probe showed excellent performance in
      high sensitivity and good selectivity towards HClO over other reactive oxygen
      species and a wide variety of coexist species in biological pH condition and had
      been successfully used to detect hypochlorous acid in serum samples and tap water
      samples.

PMID- 28501203
TI  - Development of a progesterone immunosensor based on thionine-graphene oxide
      composites platforms: Improvement by biotin-streptavidin-amplified system.
AB  - Progesterone (P4) is a kind of hormone that can cause neuropathic disturbances in
      humans when the concentration overpasses a certain degree. In this work, an
      electrochemical immunosensor capable of detecting P4 sensitively and selectively
      was developed. Thionine-graphene oxide (Thi-GO) composites with excellent
      biocompatibility were synthesized and coated to a clear glassy carbon electrode.
      P4 coating antigen (P4-OVA) was immobilized to the electrode, then sample as well
      as biotinylated antibody (biotin-P4 Ab) were added. The free P4 can compete with
      P4-OVA for binding to biotin-P4 Ab. After the further addition of streptavidin
      HRP, H2O2 was introduced to develop electrical signal for quantitative
      determination of P4. After careful optimization of assay conditions, the proposed
      immunosensor showed a linear range from 0.02 to 20ngmL-1 for P4 in milk samples.
      The averaged recoveries from spiked samples ranged from 84.0% to 102.0%, which
      correlated well with standard HPLC-MS/MS. The biosensor also showed good
      specificity, reproducibility and stability, indicating its potential application
      in monitoring of P4 in a simple and low cost manner.

PMID- 28501204
TI  - Quantification of N-glycosylation site occupancy status based on labeling/label
      free strategies with LC-MS/MS.
AB  - Protein N-glycosylation plays important roles in physiological and pathological
      processes. Characterizing the site-specific N-glycosylation including N-glycan
      macroheterogeneity (glycosylation site occupancy) and microheterogeneity (site
      specific glycan structure) is important for understanding of glycoprotein
      biosynthesis and function. N-Glycan macroheterogeneity is a physiological
      property of glycoprotein and the technical obstacles have restricted research
      into the regulation and functions of this heterogeneity. Quantification of N
      glycosylation site occupancy would uncover the critical role of
      macroheterogeneity in a variety of biological properties. Liquid chromatography
      (LC)- mass spectrometry (MS)-based quantification is emerging as a powerful tool
      for glycosylation characterization. This review summarizes the labeling and label
      free quantitative MS approaches for quantifying N-glycosylation site occupancy,
      including its quantification for target glycoproteins in recent years.

PMID- 28501205
TI  - An integrated strategy for the quantitative analysis of endogenous proteins: A
      case of gender-dependent expression of P450 enzymes in rat liver microsome.
AB  - Liquid chromatography mass spectrometry based methods provide powerful tools for
      protein analysis. Cytochromes P450 (CYPs), the most important drug metabolic
      enzymes, always exhibit sex-dependent expression patterns and metabolic
      activities. To date, analysis of CYPs based on mass spectrometry is still facing
      critical technical challenges due to the complexity and diversity of CYP isoforms
      besides lack of corresponding standards. The aim of present work consisted in
      developing a label-free qualitative and quantitative strategy for endogenous
      proteins, and then applying to the gender-difference study for CYPs in rat liver
      microsomes (RLMs). Initially, trypsin digested RLM specimens were analyzed by the
      nanoLC-LTQ-Orbitrap MS/MS. Skyline, an open source and freely available software
      for targeted proteomics research, was then used to screen the main CYP isoforms
      in RLMs under a series of criteria automatically, and a total of 40 and 39 CYP
      isoforms were identified in male and female RLMs, respectively. More importantly,
      a robust quantitative method in a tandem mass spectrometry-multiple reaction mode
      (MS/MS-MRM) was built and optimized under the help of Skyline, and successfully
      applied into the CYP gender difference study in RLMs. In this process, a simple
      and accurate approach named 'Standard Curve Slope" (SCS) was established based on
      the difference of standard curve slopes of CYPs between female and male RLMs in
      order to assess the gender difference of CYPs in RLMs. This presently developed
      methodology and approach could be widely used in the protein regulation study
      during drug pharmacological mechanism research.

PMID- 28501206
TI  - Simultaneous determination and speciation analysis of arsenic and chromium in
      iron supplements used for iron-deficiency anemia treatment by HPLC-ICP-MS.
AB  - This work proposes the use of high performance liquid chromatography coupled to
      inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for simultaneous
      speciation of arsenic and chromium in iron supplements used for the treatment of
      anemia. The sample preparation procedure recommended for the total determination
      of arsenic and chromium was established using acid digestion in a microwave
      assisted oven. For speciation analysis, however, the microwave-assisted
      extraction procedure involved the use of water as extraction solvent at 90
      degrees C for 30min. The chromatographic separation was performed using a mobile
      phase containing 1.0mM tetrabutylammonium hydroxide (TBAH), 0.7mM
      ethylenediaminetetraacetic acid (EDTA) and 5% methanol at pH 7.2. Helium was used
      in the collision cell for elimination of the interferences. Under optimized
      conditions, the separation and detection of the As(III), As(V), Cr(III) and
      Cr(VI) species can be performed in 5min, permitting their quantification with the
      external calibration technique with standards prepared in the mobile phase. The
      limits of quantification obtained were 0.008, 0.010, 0.5 and 0.14ugg-1, for
      As(III), As(V), Cr(III) and Cr(VI), respectively. The accuracy of the method was
      evaluated and confirmed by addition/recovery tests. The recoveries obtained
      varied from 81% to 110%. The proposed method was applied to the speciation
      analysis of arsenic and chromium in commercially available iron supplements
      acquired in several cities in Brazil and Spain. The content of the species ranged
      from 0.01 to 1.3ugg-1 for arsenic, and from 0.4 to 61.2ugg-1 for chromium.

PMID- 28501207
TI  - Novel bimetallic gold-silver nanoclusters with "Synergy"-enhanced fluorescence
      for cyanide sensing, cell imaging and temperature sensing.
AB  - We herein opened up a facile and green strategy for the fabrication of bright
      orange-fluorescent gold-silver nanoclusters (AuAgNCs@ew, GSNCs) by a one-pot
      synthesis at a vital molar ratio of Au/Ag precursors in the egg white protein
      matrix using microwave-assisted method. The prepared GSNCs exhibited enhanced
      fluorescence with fluorescent quantum yield of 5.4%, which is dependent on gold
      and silver synergies. Due to the advantageous superiority of low-toxicity,
      excellent stability and satisfactory fluorescence, the as-prepared GSNCs has been
      successfully used in cell imaging and temperature sensing. More strikingly, the
      GSNCs emerged strong response to CN- with rapid, selective, and ultrasensitive
      characteristics. The detection limit was approximately 138nM, which is nearly 20
      times lower than the maximum level (2700nM) of CN- in drinking water set up by
      the World Health Organization (WHO). In addition, the as-prepared GSNCs could be
      applied to detecting real samples with minimum interference. Our findings showed
      that this new GSNCs probe is eco-friendly and large-scale development for
      potential applications including the detection of environmental pollution and
      bioimaging.

PMID- 28501208
TI  - Evaluation of a QuEChERS-like extraction approach for the determination of PBDEs
      in mussels by immuno-assay-based screening methods.
AB  - A sample preparation method was evaluated for the determination of polybrominated
      diphenyl ethers (PBDEs) in mussel samples, by using colorimetric and
      electrochemical immunoassay-based screening methods. Herein, a rapid procedure
      based on QuEChERS-like extraction approach followed by solid phase purification
      was optimized for PBDE extraction from mussel samples. The detection limits for
      colorimetric and electrochemical immunoassays, calculated as BDE-47 equivalent
      concentration, were 0.6ngg-1 and 1.1ngg-1, respectively. Real mussel samples,
      including a Certified Reference Material (CRM), were analyzed. The samples were
      measured by colorimetric and electrochemical immunoassays as well as by GC-MS. In
      comparison to GC-MS results, 106% and 102% relative accuracy were obtained for
      the colorimetric and electrochemical immunoassays, respectively. The proposed
      method could be useful for massive environmental campaigns, being able to rapidly
      detect possible polluted seafood samples.

PMID- 28501209
TI  - A sensitive signal-off electrogenerated chemiluminescence biosensing method for
      the discrimination of DNA hydroxymethylation based on glycosylation modification
      and signal quenching from ferroceneboronic acid.
AB  - In this study, a new and sensitive signal-off electrogenerated chemiluminescence
      (ECL) biosensing method for the quantification of 5-hydroxymethylcytosine in DNA
      (5-hmC-DNA) was developed. The method achieved simple and sensitive detection of
      5-hmC-DNA based on the glycosylation of 5-hmC, combining both the amplification
      function of gold nanoparticles (AuNPs) and the high quenching efficiency of the
      tris(2, 2'-ripyridine) dichlororuthenium(II) (Ru(bpy)32+)-ferrocene (Fc) system.
      First, the electrode modified with a mixture of Nafion and AuNPs was utilized as
      the platform for electrostatically adsorbing Ru(bpy)32+(an ECL-emitting species)
      and assembling 5-hmC-DNA. The 5-hmC-DNA was glycosylated by T4 beta
      glucosyltransferase, yielding beta-glucosyl-5-hydroxymethyl-cytosine in DNA (5
      ghmC-DNA). Finally, quencher-FcBA was further covalently bound to 5-ghmC-DNA
      through formation of boronate ester covalent bonds between boronic acid and cis
      diols of 5-ghmC, resulting in a decrease in ECL intensity. The results indicated
      that the decreased ECL intensity was directly linear to the concentration of 5
      hmC-DNA in the range from 1.0*10-8 to 5.0*10-11M with a low detection limit of
      1.63*10-11M. In addition, this ECL method was demonstrated to be useful for the
      quantification of 5-hmC in clinical serum samples. Moreover, the method allowed
      good discrimination among cytosine (5-C), 5-methylcytosine (5-mC), and 5-hmC in
      DNA.

PMID- 28501210
TI  - Determination of tocopherols and their metabolites by liquid-chromatography
      coupled with tandem mass spectrometry in human plasma and serum.
AB  - Several studies are increasingly underlying the biological role of vitamin E
      metabolites as bioactive compounds with anti-inflammatory, anti-proliferative and
      anti-atherogenic activity. A quantitative method for the simultaneous
      determination in human plasma and serum of vitamin E (alpha-tocopherol, alpha-T
      and gamma-tocopherol, gamma-T) and its cytochrome P-450 metabolites: 13'
      hydroxychromanol (alpha-13'-OH), 13'-carboxychromanol (alpha-13'-COOH) and
      carboxyethyl hydroxychromanols (alpha-CEHC and gamma-CEHC), was developed and
      validated. After enzymatic hydrolysis and deproteinization, the metabolites were
      extracted with a mixture of hexane/ methyl tertiary butyl ether (2/1, v/v). The
      separation was achieved by reversed phase chromatography and the analytes
      detected by a triple quadrupole mass analyser using electrospray ionization in
      positive mode (LC-MS/MS). alpha-T and gamma-T were extracted separately without
      enzymatic hydrolysis. The analytes were quantified with the isotopic dilution
      method. After an extensive validation study (three levels in three different
      occasions for a total of 54 experiments), the procedure was successfully applied
      to the analysis of sera of healthy volunteers (before and after supplementation
      with alpha-T) and plasma of patients affected by chronic kidney disease. Finally,
      the structures of three unknown compounds found in blood and related to the long
      chain metabolites (alpha-13'-OH and alpha-13'-COOH) were further investigated
      using liquid chromatography coupled to high resolution mass spectrometry (LC
      HRMS).

PMID- 28501211
TI  - Metastatic cancer cell and tissue-specific fluorescence imaging using a new DNA
      aptamer developed by Cell-SELEX.
AB  - Metastasis, which derived from a primary tumor, accounts for 90% of mortality
      caused by cancer. Early diagnosis of cancer metastasis may significantly improve
      cure rate of patients who are at high risk for developing metastasis. In this
      study, we successfully achieved metastatic cancer cell and tissue-specific
      fluorescence imaging by using a new aptamer developed by cell-based systematic
      evolution of ligands by exponential enrichment (Cell-SELEX). With metastatic
      colorectal carcinoma LoVo cells as selection target, the aptamer named J3 which
      bind to metastatic cancer cells with good affinity and specificity was obtained.
      Then J3 was labeled with Cy5 fluorescent group (J3-Cy5) for imaging metastatic
      cancer cells, the results demonstrated excellent imaging contrast. Moreover, the
      results of tissue section imaging revealed that J3-Cy5 probe explicitly
      recognized lymph node tissue with colorectal carcinoma metastasis with a high
      detection rate of 73.9%, but showed a low detection rate to colorectal carcinoma
      tissue with no metastasis or cancer adjacent tissue. Therefore, the targeting
      reagent J3-based fluorescence imaging possesses great potential for clinical
      diagnosis of cancer metastasis.

PMID- 28501213
TI  - Corrigendum to "Magnetic graphene solid-phase extraction for the determination of
      carbamate pesticides in tomatoes coupled with high performance liquid
      chromatography [TAL 141 212-219]".

PMID- 28501212
TI  - A selective and sensitive fluorescent probe for the determination of HSA and
      trypsin.
AB  - A simple fluorescent probe HBI-GR based on the combination of the fluorophore (p
      HBI) in green fluorescent protein (GFP) and Guanine riboside (GR) for HSA was
      successfully synthesized. HBI-GR showed an obvious fluorescence enhancement
      toward HSA without interference from other proteins, amino acids, anions and
      commonly existing metal ions. HBI-GR exhibited high sensitivity towards HSA with
      a good linear relationship between the fluorescence intensity of HBI-GR and HSA
      concentration from 0 to 0.06mgmL-1. The limit of detection, based on a signal-to
      noise ratio of 3, was 15.09ngmL-1, which was much lower than that of most other
      reported probes. HBI-GR was almost non-fluorescent because of the bond twisting
      in the exited state of chromophore HBI. After binding to the hydrophobic pocket
      of HSA, it showed an obvious fluorescence enhancement due to the rigidifying of
      the flexible chromophore HBI by the hydrophobic environment. The resulting HBI
      GR/HSA system also showed a satisfactory sensing ability toward trypsin through
      decreased fluorescence intensity with the detection limit of 0.0282ngmL-1. The
      fluorescence decreasing process was occurred as the lysine and arginine amino
      acids residues of HSA were cleaved by trypsin, which led to further exposure of
      HBI-GR to the PBS buffer phase and a concomitant decrease of the HBI-GR
      fluorescence intensity. Moreover, the probe HBI-GR was successfully used to
      detect HSA in healthy human urine and human blood serum samples. The practical
      application of the HBI-GR/HSA system for trypsin detection in healthy human urine
      also achieved satisfactory result.

PMID- 28501215
TI  - Assessment of in vitro dopamine-neuroblastoma cell interactions with a
      bioelectric biosensor: perspective for a novel in vitro functional assay for
      dopamine agonist/antagonist activity.
AB  - Current receptor-binding assays for dopamine do not measure the in vitro whole
      cellular response against dopamine or potential agonist/antagonist molecules. We
      herewith report the development of a novel functional assay concept for studying
      the in vitro interaction of the neurotransmitter dopamine with neural cells
      bearing dopamine receptors. The concept is based on the ultra-rapid measurement
      of changes in the electric properties of cultured N2a mouse neuroblastoma cells
      (corresponding to cumulative changes of the cell membrane potential). A close
      relationship between cumulative cell membrane potential and dopamine
      concentration was observed. Membrane depolarization was observed at nanomolar
      dopamine concentrations, while hyperpolarization was associated with micromolar
      ones. Treatment with the dopamine D2-receptor antagonist eticlopride resulted to
      a concentration-dependent membrane depolarization. Treatment with sodium chloride
      caused considerable weakening of the dopamine-associated hyperpolarization
      effect. The observed bioelectric response to dopamine was highly inversely
      correlated with the pattern of dopamine release-uptake balance by N2a cells, as
      determined with cyclic voltammetry. The bioelectric approach was also used to
      evaluate the dopaminergic activity of chaste tree (Vitex agnus-castus) extracts.
      The novel assay concept offers promising perspectives for the development of
      advanced companion diagnostics system for the high throughput, fast functional
      characterization of neurotransmitter agonists and antagonists.

PMID- 28501216
TI  - Intracellular DNA and microRNA sensing based on metal-organic framework
      nanosheets with enzyme-free signal amplification.
AB  - A new fluorescent sensing platform based on ultrathin metal-organic framework
      (MOF) nanosheets (MnDMS) was prepared from the flexible ligand 2,2
      dimethylsuccinate and Mn ions. The MnDMS nanoparticles can be obtained by simply
      ultrasonication of the MnDMS crystal, and then can be exfoliated into nanosheets
      by Li-intercalation method. The MnDMS nanosheets can be easily assembled with
      biological probes, leading to efficient fluorescence quenching of the fluorophore
      tagged ssDNA and microRNA (miRNA). By using a hybridization chain reaction (HCR)
      strategy, the fluorescence signal can be obviously amplified. A good linearity
      was obtained from 1 pM to 200 pM of target ssDNA, with a detection limit of 0.2
      pM. The HCR/MnDMS system provides an effective way to monitor miRNA in living
      cells. Therefore, the MnDMS nanosheets can be used as a new kind of platform in
      biomedical sensing applications.

PMID- 28501214
TI  - Capillary electrophoresis tandem mass spectrometry determination of glutamic acid
      and homocysteine's metabolites: Potential biomarkers of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects
      both lower and upper motor neurons, leading to muscle atrophy, paralysis, and
      death caused by respiratory failure or infectious complications. Altered levels
      of homocysteine, cysteine, methionine, and glutamic acid have been observed in
      plasma of ALS patients. In this context, a method for determination of these
      potential biomarkers in plasma by capillary electrophoresis tandem mass
      spectrometry (CE-MS/MS) is proposed herein. Sample preparation was carefully
      investigated, since sulfur-containing amino acids may interact with plasma
      proteins. Owing to the non-thiol sulfur atom in methionine, it was necessary to
      split sample preparation into two methods: i) determination of homocysteine and
      cysteine as S-acetyl amino acids; ii) determination of glutamic acid and
      methionine. All amino acids were separated within 25min by CE-MS/MS using 5molL-1
      acetic acid as background electrolyte and 5mmolL-1 acetic acid in 50%
      methanol/H2O (v/v) as sheath liquid. The proposed CE-MS/MS method was validated,
      presenting RSD values below 6% and 11% for intra- and inter-day precision,
      respectively, for the middle concentration level within the linear range. The
      limits of detection ranged from 35 (homocysteine) to 268nmolL-1 (glutamic acid).
      The validated method was applied to the analysis of plasma samples from a group
      of healthy individuals and patients with ALS, showing the potential of glutamic
      acid and homocysteine metabolites as biomarkers of ALS.

PMID- 28501217
TI  - EDTA-functionalized magnetic nanoparticles: A suitable platform for the analysis
      of low abundance urinary proteins.
AB  - Urine is a highly attractive source of biological information and disease
      biomarkers, whose proteome characterization is ongoing. To that end,
      depletion/enrichment strategies for protein analysis can be of great convenience.
      We have thus developed a method based on the use of EDTA-functionalized magnetic
      nanoparticles (NPs@EDTA), to fractionate urine samples before liquid
      chromatography-mass spectrometry analysis and compared the identified proteins
      with those obtained from ultrafiltrated/unfractionated (UF) urine samples.
      NPs@EDTA allowed larger urine volumes to be processed, resulting in a greater
      number of protein identifications (~2-fold) at a lower cost when compared to UF
      samples. Proteins of greater abundance (such as albumin and uromodulin) were, at
      least partially, depleted with NPs@EDTA while those of lower abundance were
      enriched. Bioinformatics analysis showed that approximately 27% of NPs@EDTA
      enriched proteins were annotated as displaying enzymatic activity, most of these
      being hydrolytic enzymes (56%), particularly proteases/peptidases (48%). Also,
      post-translational modifications were prominently predicted across NPs@EDTA
      enriched proteins (90%), particularly glycosylation (52%), phosphorylation (47%)
      and acetylation (30%). NPs@EDTA allowed the identification of 109 proteins in
      urine for the first time, showing high potential as a platform for urine's
      fractionation prior to proteomic analysis.

PMID- 28501218
TI  - A modified fluorescein derivative with improved water-solubility for turn-on
      fluorescent determination of Hg2+ in aqueous and living cells.
AB  - To improve the water-solubility of heavy-metal sensing materials, a modified
      fluorescein-based derivative, acryloyl fluorescein hydrazine (ACFH), was designed
      and developed by incorporating a non-hydrogen-bonding group into the conjugated
      molecule for weakening intermolecular hydrogen-bonding interactions. In neutral
      water environments, ACFH presented a fluorescence-enhancement performance at
      lambdamax=512nm in the presence of Hg2+, which could be visualized by naked-eyes.
      Under the optimized conditions, the linear range of Hg2+ detection was 1.0-100*10
      9molL-1 with a correlation coefficient of 0.9992 and a detection limit of 0.86*10
      9molL-1. The recognition mechanism was confirmed to be a stable and irreversible
      1:1 five-member ring complex between ACFH and Hg2+ with a coordination constant
      of 3.36*109. ACFH would possess a potential application in detecting Hg2+ for
      biological assay with low cytotoxicity.

PMID- 28501219
TI  - Headspace single-drop microextraction coupled with microvolume fluorospectrometry
      for highly sensitive determination of bromide.
AB  - This work reports on the development of a novel methodology for bromide
      determination by combining headspace single-drop microextraction with microvolume
      fluorospectrometry. The method lies in the in situ generation of bromine,
      transfer of the volatile to the headspace and trapping/reaction onto a
      fluorescein-containing aqueous drop exposed to the gas phase. The decrease in the
      fluorescence intensity enabled the determination of bromide without dilution of
      the enriched microdrop. Experimental parameters influencing the performance of
      the method, namely, fluorescence parameters, extractant phase composition,
      bromine generation conditions and microextraction time, were evaluated and
      controlled. Under optimal conditions, an enrichment factor of 243 was attained.
      The limits of detection and quantification achieved under optimal conditions for
      bromide were found to be 1.4 and 4.4ugL-1, respectively. The intra-day
      repeatability, expressed as relative standard deviation, was 4.4% (n=6). Besides,
      the inter-day reproducibility, performed at four different days, was 7.1%.
      Finally, the developed method was successfully applied to the determination of
      bromide in different water samples, showing recovery values in the range of 95
      110%, and validated against certified reference material BCR-611 (ground water,
      Br- low level). The proposed method represents a highly convenient approach for
      monitoring of bromide at very low concentrations.

PMID- 28501220
TI  - 7,8-hydroxy-2'-deoxyguanosine/2'-deoxiguanosine ratio determined in hydrolysates
      of brain DNA by ultrachromatrography coupled to tandem mass spectrometry.
AB  - 7,8-hydroxy-2'-deoxyguanosine (8-OHdG) is an abundant DNA lesion formed by
      oxidation of the nucleoside 2'-deoxyguanosine (2-dG) and one of the most studied
      and accepted oxidative stress biomarkers. 8-OHdG has a strong carcinogenic
      potential, and prolonged oxidative stress heightens pathological conditions and
      especially cancer risk. Our aim was to develop, validate and apply a reliable
      method to assess DNA oxidation in genomic cellular DNA of sensible target organs
      such as brain. A procedure to isolate and digest the DNA of brain tissue properly
      for further detection of 8-OHdG and 2-dG by Ultra Performance Liquid
      Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) was optimized. The UPLC
      MS/MS was validated following the American Food and Drug Administration (FDA)
      Guidelines using mice pups' brain samples. To demonstrate the applicability of
      the UPLC-MS/MS method, 8-OHdG/2-dG ratio was determined in brain tissue of 1day
      old newborn mice pups (P1) in a model of hypoxia pre-conditioning during fetal-to
      neonatal transition. We found that hypoxia at birth (FiO2 0.14) and for 8h
      thereafter induced lower levels of DNA oxidation in mice pups and rendered even
      protective against a postnatal asphyxia/reoxygenation insult compared with fetal
      to neonatal transition in room air. We conclude that the UPLC-MS/MS method
      developed has proven suitable for the analysis of DNA oxidation biomarker 8
      OHdG/2-dG ratio in tissue samples from newborn mice pups. We aim to apply this
      method in future studies aiming to provide a deeper insight into the mechanisms
      of oxidation DNA caused during neonatal asphyxia and resuscitation.

PMID- 28501221
TI  - Return to Sport and Clinical Outcomes After Hip Arthroscopic Labral Repair in
      Young Amateur Athletes: Minimum 2-Year Follow-Up.
AB  - PURPOSE: To determine the rate of return of young amateur athletes to sport after
      hip arthroscopy, their clinical outcomes, and pathologic risk factors for worse
      outcomes 2 years after surgery. METHODS: This study included all patients between
      age 13 and 23 who participated in a sport prior to surgery with intent to return
      who underwent hip arthroscopy after failure of comprehensive nonoperative
      management for whom 2-year outcome scores were available. Outcomes collected
      retrospectively included modified Harris Hip Score (mHHS) and the Hip Outcome
      Scores (HOS) subscales for activities of daily living (ADL) and sport (HOS
      Sport). In addition, sport played, return to sport rates, and Tegner Scores were
      measured preinjury and postoperatively. Descriptive statistics were used to
      present demographic data. A priori analysis was used to determine the sample size
      needed to show minimal clinically important differences for mHHS, HOS ADL, and
      HOS Sport. RESULTS: The study population included 50 patients with a mean age of
      17.8 years. Athletes returned to sport at a rate of 92% (46/50). At a mean follow
      up of 34 months, the mean mHHS, HOS ADL, and HOS Sport outcome scores were 85,
      91, and 80 for the entire study group; 87, 92, and 84 for the group that returned
      to sport; and 67, 82, and 41 for the group that did not return to sport,
      respectively. Median preinjury and postoperative Tegner levels were 8 and 7,
      respectively. Labral takedown and reattachment was associated with lower HOS ADL
      (P = .01) and HOS Sport scores (P = .02). CONCLUSIONS: Athletes returned to sport
      at a high rate (92%; 46/50) after hip arthroscopy and perform activities at near
      preinjury levels. In this group of athletes, arthroscopic labral repair with
      chondrolabral preservation, which reflected less severe chondrolabral pathology,
      performed better than labral repair with takedown and reattachment. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 28501222
TI  - Medial Patellar Instability: A Systematic Review of the Literature of Outcomes
      After Surgical Treatment.
AB  - PURPOSE: To perform a systematic review of literature reporting on outcomes after
      surgical treatment of medial patellar instability. METHODS: A systematic review
      was performed according to PRISMA guidelines. Inclusion criteria were as follows:
      the outcomes and complications of medial patellar instability repair with a
      follow-up greater than 12 months, English language, and human studies. We
      excluded cadaveric studies, animal studies, basic science articles, editorial
      articles, review articles, and surveys. RESULTS: Searches identified 1,116
      individual titles. After inclusion and exclusion criteria were applied, a total
      of 8 studies were identified. Three studies exclusively included patients with
      previous lateral release; 1 included patients with chronic instability; 1
      included patients with both previous lateral release and other surgical causes; 1
      study had patients with previous lateral release, spontaneous instability, and
      instability due to injury; 1 study included patients after tibial tubercle
      transfer surgery; and 1 study did not report the etiology of instability.
      CONCLUSIONS: Good to excellent outcomes were reported postoperatively in 85% of
      the patients after surgical treatment of medial patellar instability. However,
      clinical outcomes data for medial patellar ligament reconstruction is sparse and
      highly heterogeneous. There is inconsistency in the literature in regard to the
      indication, timing, and procedure. LEVEL OF EVIDENCE: Level IV, systematic review
      of Level IV studies.

PMID- 28501223
TI  - Health care barriers, racism, and intersectionality in Australia.
AB  - While racism has been shown to negatively affect health care quality, little is
      known about the extent to which racial discrimination works with and through
      gender, class, and sexuality to predict barriers to health care (e.g., perceived
      difficulty accessing health services). Additionally, most existing studies focus
      on racial disparities in the U.S. context, with few examining marginalized groups
      in other countries. To address these knowledge gaps, we analyze data from the
      2014 Australian General Social Survey, a nationally representative survey of
      individuals aged 15 and older living in 12,932 private dwellings. Following an
      intersectional perspective, we estimate a series of multivariable logit
      regression models to assess three hypotheses: racial discrimination will be
      positively associated with perceived barriers to health care (H1); the effect of
      perceived racial discrimination will be particularly severe for women, sexual
      minorities, and low socio-economic status individuals (H2); and, in addition to
      racial discrimination, other forms of perceived discrimination will negatively
      impact perceived barriers to health care (H3). Findings show that perceptions of
      racial discrimination are significantly associated with perceived barriers to
      health care, though this relationship is not significantly stronger for low
      status groups. In addition, our analyses reveal that perceived racism and other
      forms of discrimination combine to predict perceived barriers to health care.
      Taken together, these results speak to the benefits of an intersectional approach
      for examining racial inequalities in perceived access to health care.

PMID- 28501224
TI  - Re: Pascal Rischmann, Albert Gelet, Benjamin Riche, et al. Focal High Intensity
      Focused Ultrasound of Unilateral Localized Prostate cancer: A Prospective
      Multicentric Hemiablation Study of 111 Patients. Eur Urol 2017;71:267-73.

PMID- 28501225
TI  - Introduction to Integrative Medicine in the Primary Care Setting.
AB  - Integrative Medicine has been described as "healing oriented medicine that takes
      account of the whole person (body, mind, and spirit) including all aspects of
      lifestyle. It emphasizes therapeutic relationships and makes use of all
      appropriate therapies, both conventional and alternative." National surveys
      consistently report that approximately one-third of adults and 12% of children
      use complementary and integrative medicine approaches. Although there are
      barriers to primary care professionals engaging in discussions about lifestyle
      change and complementary and integrative medicine options, there is also great
      potential to impact patient well-being.

PMID- 28501226
TI  - Phytotherapy: An Introduction to Herbal Medicine.
AB  - Herbal medications are commonly used in all medical settings, making it essential
      for primary care providers to learn about the products being used and resources
      they can access for continuing education. Understanding how herbal medicines are
      sourced, processed, and standardized can help providers guide patients who are
      trying to choose the most clinically effective and affordable treatments.
      Multiple herbs are often combined and sold as proprietary blends, which can
      increase the risk of allergies, adverse reactions, or cross-reactivity with other
      pharmaceuticals and supplements. Several textbooks, online point-of-care
      resources, and conferences are available for primary care providers to expand
      their knowledge of herbal medicines.

PMID- 28501227
TI  - Integrative Medicine Strategies for Changing Health Behaviors: Support for
      Primary Care.
AB  - Until system reforms allow adequate time and reimbursement for primary care
      providers to focus on lifestyle change to prevent and mitigate chronic disease,
      primary care providers need a manageable, defined role to support lifestyle
      change. The authors suggest this role is to serve as a catalyst, priming the
      patient for change; educating and pointing the patient to appropriate, evidence
      based resources for additional guidance and hands-on support; and providing
      ongoing encouragement throughout the long journey of change while patients work
      more intensely with health coaches or allied health providers.

PMID- 28501228
TI  - Integrative Medicine for the Treatment of Persistent Pain.
AB  - Integrative health modalities can provide useful tools in the management of
      persistent pain in the primary care setting. These modalities, such as
      acupuncture, mind-body medicine, diet and herbs, and movement strategies can be
      safely used and may provide patients with hope and empowerment. It is highly
      recommended that the patient work alongside trained professionals for a given
      modality and/or an interprofessional team.

PMID- 28501230
TI  - Integrative Medicine and Mood, Emotions and Mental Health.
AB  - An integrative approach to individuals with mood, emotional or mental health
      concerns involves a comprehensive model of care that is person-centered.
      Integrative medicine builds on a patient's personal meaning and goals (spiritual
      aspects) and includes herbal therapies, nutritional support, movement and
      physical manipulative therapies, mindfulness, relaxation strategies, and
      psychotherapies.

PMID- 28501231
TI  - Complementary and Integrative Interventions for Chronic Neurologic Conditions
      Encountered in the Primary Care Office.
AB  - Chronic neurologic conditions are frequently managed in the primary care setting,
      and patients with these conditions are increasingly seeking nonconventional
      treatment options. This article provides a review and summary of the evidence for
      some of the most commonly studied and most frequently used complementary and
      integrative interventions for 3 conditions managed every day in primary care
      offices - diabetic neuropathy, migraine, and dementia.

PMID- 28501232
TI  - Restoring Balance for People with Cancer Through Integrative Oncology.
AB  - Integrative Oncology incorporates conventional and western cancer treatment
      approaches with the best of ancient and traditional medicine including nutrition,
      supplements, Qigong, herbal medicine, mind-body practices, and more. This article
      offers a guiding conceptual paradigm from an integrative perspective based on the
      principles of balance and imbalance. An integrative approach is used to help
      improve quality of life, enhance lifestyle choices and mitigate symptoms and side
      effects from conventional treatments. By supporting the patient's mind, body and
      spirit throughout the cancer treatment journey, the primary care physician is in
      a key position to work with their patient's oncologist to provide supportive care
      and recommendations during cancer treatment.

PMID- 28501229
TI  - Integrative Medicine for Gastrointestinal Disease.
AB  - Gastrointestinal conditions are prevalent in the population and account for
      significant morbidity and health care costs. Patients with gastrointestinal
      conditions use integrative medicine. There is growing evidence that integrative
      medicine approaches can improve symptoms and affect physiology and disease
      course. This article reviews data on some common and well-studied approaches,
      including mind-body therapies, acupuncture, diet, probiotics, and dietary
      supplements and herbs. Although clear recommendations can be made for some
      conditions, in others there are challenges in translating these findings owing to
      small study size, lack of standardization, and trial heterogeneity.

PMID- 28501233
TI  - Pediatric Integrative Medicine.
AB  - The practice of pediatrics from an integrative framework is based on physician
      patient relationship, informed by evidence, and approaches the health of children
      and their families from a broad perspective. This article reviews the basic
      principles of integrative pediatrics and summarizes data and integrative
      approaches to common pediatric conditions seen in the primary care setting.

PMID- 28501234
TI  - Integrative Medicine and Cardiovascular Disorders.
AB  - Integrative medicine (IM) has developed an increasingly significant role in
      health care worldwide, including cardiovascular diseases (CVD). This review
      describes the commonly used IM in CVD, with particular attention placed with
      dietary supplements and mind-body therapies. More rigorous research continues to
      be needed to determine the mechanisms and efficacy of IM cardiovascular morbidity
      and mortality. Health care providers will need to develop skills in open
      communication and nonjudgmental dialogue around IM use in discussing treatment
      plans with their patients.

PMID- 28501235
TI  - Women's Health: Pregnancy and Conception.
AB  - Preconception is an ideal time to assist women contemplating pregnancy to modify
      health behaviors. Dietary needs in pregnancy are critical and may require
      supplementation. The use of mind-body medicine in the antenatal period assists
      patients in childbirth preparation. Integrative medicine techniques can be safely
      and effectively used for common third-trimester obstetric complications of
      pregnancy.

PMID- 28501236
TI  - Women's Health: Polycystic Ovarian Syndrome, Menopause, and Osteoporosis.
AB  - Surveys consistently show that a significantly higher percentage of women with
      chronic medical conditions report use of complementary and integrative medicine
      (CIM) approaches compared with men. A total of 54.5% of women report use of at
      least one CIM approach specifically for obstetric or gynecologic problems.
      However, primary care providers remain an underutilized resource by patients for
      guidance in the safe and appropriate use of integrative therapies. This article
      provides a practical overview of the most appropriate integrative therapies to
      consider in the management of commonly seen women's health conditions: polycystic
      ovarian syndrome, menopause, and osteoporosis.

PMID- 28501237
TI  - "Too Much?"

PMID- 28501238
TI  - Integrative Medicine and Primary Care.

PMID- 28501239
TI  - Economic Insecurity and Intimate Partner and Sexual Violence Victimization.
AB  - INTRODUCTION: Previous research has consistently found that low SES is associated
      with higher levels of both intimate partner violence (IPV) and sexual violence
      (SV) victimization. Though associated with poverty, two indicators of economic
      insecurity, food and housing insecurity, have been identified as conceptually
      distinct social determinants of health. This study examined the relationship
      between food and housing insecurity experienced in the preceding 12 months and
      IPV and SV victimization experienced in the preceding 12 months, after
      controlling for SES and other demographic variables. METHODS: Data were from the
      2010 National Intimate Partner and Sexual Violence Survey, a nationally
      representative telephone survey of U.S. adults. In 2016, multivariate logistic
      regression modeling was used to examine the association between food and housing
      insecurity and multiple forms of IPV and SV victimization. RESULTS: Robust
      associations were found between food and housing insecurity experienced in the
      preceding 12 months and IPV and SV experienced in the preceding 12 months, for
      women and men, even after controlling for age, family income, race/ethnicity,
      education, and marital status. CONCLUSIONS: Food and housing insecurity may be
      important considerations for the prevention of SV and IPV or the reductions of
      their consequences, although future research is needed to disentangle the
      direction of the association. Strategies aimed at buffering economic insecurity
      may reduce vulnerability to IPV and SV victimization.

PMID- 28501240
TI  - Urinary Excretion of alpha1-Microglobulin Does Not Predict Graft Loss in Stable
      Kidney Transplant Recipients.

PMID- 28501241
TI  - In Reply to 'Urinary Excretion of alpha1-Microglobulin Does Not Predict Graft
      Loss in Stable Kidney Transplant Recipients'.

PMID- 28501242
TI  - Colorectal Cancer Screening.
AB  - This article highlights the importance of colorectal cancer screening in the
      prevention and early detection of colorectal cancer. Early detection of
      colorectal cancer is associated with reduced mortality. There are a variety of
      screening procedures for colorectal cancer, which are variable in technique and
      effectiveness. Engaging patients to participate in a screening regimen with which
      they will comply is critical to the ultimate success of colorectal cancer
      screening. Familiarity with risk stratification and screening guidelines is
      imperative for counseling and appropriate testing.

PMID- 28501243
TI  - Imaging for Colorectal Cancer.
AB  - A comprehensive approach to colorectal cancer includes thorough radiologic
      imaging, which allows appropriate initial staging of the disease, as well as
      subsequent surveillance for disease recurrence. Several imaging modalities are
      used with different associated advantages and disadvantages, which are outlined
      in this article with specific attention paid to the local staging of rectal
      cancer.

PMID- 28501244
TI  - The Difficult Colorectal Polyp.
AB  - Difficult colorectal polyps represent lesions that pose a challenge to
      traditional endoscopic snare polypectomy. These polyps have historically been
      managed by surgical resection. Currently, several less invasive options are
      available to avoid colectomy. Repeat colonoscopy and snare polypectomy by an
      expert endoscopist, endoscopic mucosal resection, endoscopic submucosal
      dissection, and combined endoscopic and laparoscopic surgery have been developed
      to remove difficult polyps without the need for formal surgical resection.
      Patients with rectal polyps have the advantage of additional transanal minimally
      invasive techniques to enhance their resectability. Today, most colorectal polyps
      can be managed without the need for formal surgical resection.

PMID- 28501245
TI  - Emergency Presentations of Colorectal Cancer.
AB  - Many colorectal carcinomas will present emergently with issues such as
      obstruction, perforation, and bleeding. Emergency surgery is associated with poor
      short- and long-term outcomes. For abnormality localizing to the colon proximal
      to the splenic flexure, surgical management with hemicolectomy is often a safe
      and appropriate approach. Obstructions are more common in the distal colon,
      however, where there is an evolving spectrum of surgical and nonsurgical options,
      most notably by the development of endoluminal stents. Perforation and bleeding
      are managed similarly to benign causes, as malignancy may be only part of a
      differential diagnosis at the time of an operation.

PMID- 28501247
TI  - Robotic Colorectal Surgery for Neoplasia.
AB  - Robotic colorectal surgery has become increasingly prevalent, with several
      reported benefits for surgeons and patients alike. Although its use is well
      supported for pelvic surgery, there is less evidence that it is beneficial for
      abdominal surgery. There are several technical limitations of robotic surgery,
      and newer generations of robot platforms have addressed these, which may lead to
      increased use in the near future. In general, robotic surgery is more beneficial
      for surgeons than it is for patients.

PMID- 28501246
TI  - Advances in Laparoscopic Colorectal Surgery.
AB  - Laparoscopic colorectal surgery has now become widely adopted for the treatment
      of colorectal neoplasia, with steady increases in utilization over the past 15
      years. Common minimally invasive techniques include multiport laparoscopy, single
      incision laparoscopy, and hand-assisted laparoscopy, with the choice of technique
      depending on several patient and surgeon factors. Laparoscopic colorectal surgery
      involves a robust learning curve, and fellowship training often lays the
      foundation for a high-volume laparoscopic practice. This article provides a
      summary of the various techniques for laparoscopic colorectal surgery, including
      operative steps, the approach to difficult patients, and the learning curve for
      proficiency.

PMID- 28501248
TI  - Local Excision of Rectal Cancer.
AB  - Local excision (LE) of early-stage rectal cancer avoids the morbidity associated
      with radical surgery but has historically been associated with inferior oncologic
      outcomes. Newer techniques, including transanal endoscopic microsurgery (TEM) and
      transanal minimally invasive surgery (TAMIS), have been developed to improve the
      quality of LE and extend the benefits of LE to tumors in the more proximal
      rectum. This article provides an overview of conventional LE, TEM, and TAMIS
      techniques, including indications for their use and pertinent literature on their
      associated outcomes for rectal cancer.

PMID- 28501249
TI  - New Strategies in Rectal Cancer.
AB  - In recent years, our understanding of rectal cancer has improved, including how
      locally advanced disease responds to chemotherapy and radiation. This has led to
      new innovations and advances in the treatment of rectal cancer, which includes
      organ-preserving strategies for responsive disease, and minimally invasive
      approaces for the performance of total mesorectal excision/protectomyh for
      persistently advanced disease. This article discusses new strategies for rectal
      cancer therapy, including Watch and Wait, local excision, minimally invasive
      proctectomy, and transanal total mesorectal excision particularly in the setting
      of preoperative multimodality treatment.

PMID- 28501250
TI  - Hereditary Colorectal Cancer Syndromes.
AB  - Awareness of hereditary colorectal cancer syndromes is important to facilitate
      their identification because affected patients are at increased risk for early
      onset, synchronous, and metachronous colorectal malignancies, and certain
      extracolonic malignancies depending on the syndrome. Identification of an
      affected individual allows for screening and early interventions for patients and
      their at-risk kindred. Genetic counseling and testing is important to the care of
      these patients. As knowledge of the genetic basis of these syndromes grows,
      unique genotype-phenotype profiles allow clinicians to tailor surveillance and
      treatment strategies based on individual risk.

PMID- 28501251
TI  - Dysplasia and Cancer in Inflammatory Bowel Disease.
AB  - Inflammatory bowel disease is associated with an increased risk of dysplasia and
      cancer. Improvements in medical management and endoscopic surveillance have
      reduced these risks. Patients can develop cancer even in the absence of dysplasia
      or with indefinite or low-grade dysplasia. Most guidelines recommend starting
      surveillance colonoscopy 6 to 10 years after initial diagnosis with interval
      surveillance afterward every 1 to 5 years depending on risk and/or individual
      characteristics. Most patients should undergo total proctocolectomy with end
      ileostomy or reconstruction with ileal pouch anal anastomosis because segmental
      and subtotal resections carry a higher risk of metachronous cancers.

PMID- 28501252
TI  - Atypical Colorectal Neoplasms.
AB  - Primary colorectal lymphoma, carcinoids (neuroendocrine tumors), and
      gastrointestinal stromal tumors comprise a small subset of all colorectal
      cancers. Their features are unique, and their treatment varies from that of
      colorectal adenocarcinoma. Appropriate identification is key in the management of
      these tumors.

PMID- 28501254
TI  - Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy in the Management of
      Colorectal Peritoneal Metastasis.
AB  - Historically, patients with peritoneal carcinomatosis secondary to colorectal
      cancer have a poor overall prognosis. Recent data support the use of
      cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) to
      specifically address the peritoneal disease. Retrospective studies on CRS + HIPEC
      have been promising, showing significant improvements in OS compared with
      systemic chemotherapy alone. However, CRS + HIPEC carries morbidity similar to
      other advance oncology procedures such as liver resection and
      pancreatoduonectomy. It is hoped that ongoing clinical trials will clarify its
      role in the treatment of patients with peritoneal metastatic colorectal cancer.

PMID- 28501253
TI  - Resection of the Primary Tumor in Stage IV Colorectal Cancer: When Is It
      Necessary?
AB  - Management of metastatic colorectal cancer requires accurate staging and
      multidisciplinary evaluation, leading to a consensus treatment plan with the
      ultimate goal of increasing survival and improving the quality of life, while
      taking into consideration the patient's performance status, disease burden, and
      goals of care. Since the introduction of multidrug chemotherapeutic regimens,
      survival of patients with metastatic colorectal cancer has improved. Many
      patients with unresectable disease are undergoing surgery for asymptomatic
      primary tumors despite evidence that it is usually a futile intervention.
      Palliative measures for local control of the primary tumor include colonic
      stents, laser therapy, and fulguration.

PMID- 28501256
TI  - Foreword.

PMID- 28501255
TI  - Molecular Markers for Colorectal Cancer.
AB  - Colorectal cancers develop through at least 3 major pathways, including
      chromosomal instability, mismatch repair, and methylator phenotype. These
      pathways can coexist in a single individual and occur in both sporadic and
      inherited colorectal cancers. In spite of the unique molecular and genetic
      signatures of colorectal cancers, nonspecific chemotherapy based on the
      antineoplastic effects of 5-fluorouracil is the cornerstone of therapy for stage
      III and some stage II disease. Techniques to recognize colorectal cancer at the
      molecular level have facilitated development of new signature drugs designed to
      inhibit the unique pathways of colorectal cancer growth and immunity.

PMID- 28501257
TI  - Preface.

PMID- 28501258
TI  - Impact of Hospital Admission for Patients with Transient Ischemic Attack.
AB  - OBJECTIVES: To determine the impact of admission among transient ischemic attack
      (TIA) patients in the emergency department (ED). STUDY DESIGN: Retrospective
      cohort study using national Veterans Health Administration data (2008). METHODS:
      We first analyzed whether admitted patients were discharged from the hospital
      with a diagnosis of TIA. We then analyzed whether admission was associated with a
      composite outcome (new stroke, new myocardial infarction, or death in the year
      after TIA) using multivariate logistic regression modeling with propensity score
      matching. RESULTS: Among 3623 patients assigned a diagnosis of TIA in the ED,
      2118 (58%) were admitted to the hospital or placed in observation compared with
      1505 (42%) who were discharged from the ED. Among the 2118 patients who were
      admitted, 903 (43% of admitted group) were discharged from the hospital with a
      diagnosis of TIA, and 548 (26% of admitted group) were discharged with a
      diagnosis of stroke. Admitted patients were more likely than nonadmitted patients
      to receive processes of care (i.e., brain imaging, carotid imaging,
      echocardiography). In matched analyses using propensity scores, the 1-year
      composite outcome in the admitted group (15.3%) was not lower than the discharged
      group (13.3%, OR 1.17 [.94-1.46], P = .17). CONCLUSIONS: Less than half of
      patients admitted with a diagnosis of TIA retained that diagnosis at hospital
      discharge. Although admitted patients were more likely to receive diagnostic
      procedures, we did not identify improvements in outcomes among admitted patients;
      however, evaluating care for patients with TIA is limited by the reliability of
      secondary data analysis.

PMID- 28501260
TI  - Erratum to "Efficacy and tolerability of adjunctive brivaracetam in patients with
      prior antiepileptic drug exposure: A post-hoc study" [Epilepsy Res. 131 (2017) 70
      75].

PMID- 28501259
TI  - Risk of Stroke/Transient Ischemic Attack or Myocardial Infarction with Herpes
      Zoster: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Accumulating evidence indicates that herpes zoster (HZ) may increase
      the risk of stroke/transient ischemic attack (TIA) or myocardial infarction (MI),
      but the results are inconsistent. We aim to explore the relationship between HZ
      and risk of stroke/TIA or MI and between herpes zoster ophthalmicus (HZO) and
      stroke. METHODS: We estimated the relative risk (RR) and 95% confidence intervals
      (CIs) with the meta-analysis. Cochran's Q test and Higgins I2 statistic were used
      to check for heterogeneity. RESULTS: HZ infection was significantly associated
      with increased risk of stroke/TIA (RR = 1.30, 95% CI: 1.17-1.46) or MI (RR =
      1.18, 95% CI: 1.07-1.30). The risk of stroke after HZO was 1.91 (95% CI 1.32
      2.76), higher than that after HZ. Subgroup analyses revealed increased risk of
      ischemic stroke after HZ infection but not hemorrhagic stroke. The risk of stroke
      was increased more at 1 month after HZ infection than at 1-3 months, with a
      gradual reduced risk with time. The risk of stroke after HZ infection was greater
      with age less than 40 years than 40-59 years and more than 60 years. Risk of
      stroke with HZ infection was greater without treatment than with treatment and
      was greater in Asia than Europe and America but did not differ by sex.
      CONCLUSIONS: Our study indicated that HZ infection was associated with increased
      risk of stroke/TIA or MI, and HZO infection was the most marked risk factor for
      stroke. Further studies are needed to explore whether zoster vaccination could
      reduce the risk of stoke/TIA or MI.

PMID- 28501261
TI  - Obsessive Compulsive Symptoms and Quality of Life in mothers of Children With
      Atopic Dermatitis.
AB  - BACKGROUND AND OBJECTIVES: Atopic dermatitis is one of the most common skin
      disorders in children and it can negatively affect both children and their
      families. The purpose of this study was to investigate the effect of atopic
      dermatitis on quality of life related to maternal health and maternal obsessive
      compulsive symptoms. METHODS: A cross-sectional study was conducted in the
      pediatric and dermatology polyclinics. The SCORAD index was used for determining
      the severity of disease, and the Maudsley Obsessive Compulsive Inventory (MOCI)
      and SF-36 form were applied to the participants' mothers. RESULTS: A total of 120
      children and their mothers participated the study. Comparing the atopic
      dermatitis group and the healthy control group, no statistically significant
      differences were seen in terms of MOCI and SF-36 scores, except for the physical
      functioning subscore. CONCLUSION: The results showed that having a child with
      atopic dermatitis and the severity of the disease do not influence their mothers
      in terms of obsessive-compulsive symptoms and health-related quality of life,
      except for physical functioning scores.

PMID- 28501262
TI  - Radiotherapy in nonmelanoma skin cancer: Radiosensitivity, radioresistance and
      radiocurability. In regard to Gracia-Cazana et al.

PMID- 28501263
TI  - Economic and environmental review of Waste-to-Energy systems for municipal solid
      waste management in medium and small municipalities.
AB  - The application of Directive 2008/98/CE on Municipal Solid Waste (MSW) implies
      the need to introduce technologies to generate energy from waste. Incineration,
      the most widely used method, is difficult to implement in low populated areas
      because it requires a large amount of waste to be viable (100,000 tons per year).
      This paper analyses the economic and environmental costs of different MSW-to
      Energy technologies (WtE) in an area comprising of 13 municipalities in southern
      Spain. We analyse anaerobic digestion (Biomethanization), the production of solid
      recovered fuel (SRF) and gasification, and compare these approaches to the
      present Biological Mechanical Treatment (BMT) with elimination of the reject in
      landfill, and incineration with energy recovery. From an economic standpoint the
      implementation of WtE systems reduces the cost of running present BMT systems and
      incineration; gasification presents the lowest value. From the environmental
      standpoint, Life Cycle Assessment shows that any WtE alternatives, including
      incineration, present important advantages for the environment when compared to
      BMT. Finally, in order to select the best alternative, a multi-criteria method is
      applied, showing that anaerobic digestion is the optimal solution for the area
      studied.

PMID- 28501264
TI  - Challenges around automotive shredder residue production and disposal.
AB  - The challenge for the automotive industry is how to ensure they adopt the
      circular economy when it comes to the disposal of end-of-life vehicles (ELV).
      According to the European Commission the UK achieved a total reuse and recovery
      rate of 88%. This is short of the revised ELV directive target of 95% materials
      recovery, which requires a minimum of 85% of materials to be recycled or reused.
      A significant component of the recycling process is the production of automotive
      shredder residue (ASR). This is currently landfilled across Europe. The
      additional 10% could be met by processing ASR through either waste-to-energy
      facilities or Post shredder technology (PST) to recover materials. The UK auto
      and recycling sectors claimed there would need to be a massive investment by
      their members in both new capacity and new technology for PST to recover
      additional recycle materials. It has been shown that 50% of the ASR contains
      valuable recoverable materials which could be used to meet the Directive target.
      It is expected in the next 5years that technological innovation in car design
      will change the composition from easily recoverable metal to difficult polymers.
      This change in composition will impact on the current drive to integrate the
      European Circular Economy Package. A positive factor is that main driver for
      using ASR is coming from the metals recycling industry itself. They are looking
      to develop the infrastructure for energy generation from ASR and subsequent
      material recovery. This is driven by the economics of the process rather than
      meeting the Directive targets. The study undertaken has identified potential
      pathways and barriers for commercial thermal treatment of ASR. The results of ASR
      characterisation were used to assess commercial plants from around the world.
      Whilst there were many claiming that processing of ASR was possible none have so
      far shown both the technological capability and economic justification.

PMID- 28501265
TI  - An algorithm for the management of coagulopathy from postpartum hemorrhage, using
      fibrinogen concentrate as first-line therapy.
AB  - BACKGROUND: We constructed an algorithm for the management of coagulopathy from
      massive postpartum hemorrhage. Fibrinogen concentrate was administered
      preferentially, and the dose of both fibrinogen concentrate and fresh frozen
      plasma given was determined by the plasma fibrinogen concentration and
      prothrombin time. The efficacy of the algorithm and the amount of fibrinogen
      concentrate and fresh frozen plasma transfused were determined. METHODS: The
      study was conducted in a single teaching perinatal center. Nineteen patients were
      included between April 2011 and March 2014 (patient group). For a historical
      comparison group, we retrospectively analyzed the records of 19 patients who had
      been treated for coagulopathy from massive postpartum hemorrhage between April
      2006 and March 2011 (control group). RESULTS: Blood loss was significantly lower
      in the patient group. No adverse events were associated with this management in
      either group. The dose of fibrinogen concentrate administered was significantly
      higher and that of fresh frozen plasma administered was significantly lower in
      the patient group. CONCLUSION: This algorithm appeared to help reduce blood loss
      and the total amount of fresh frozen plasma transfused when treating coagulopathy
      from postpartum hemorrhage, and may represent another strategy for achieving
      hemostasis in this setting.

PMID- 28501266
TI  - Cochleotoxicity monitoring protocol.
AB  - INTRODUCTION: Cochlear damage is frequent in long-term aminoglycosides therapy or
      chemotherapeutic treatments with platinum-based agents. Despite its prevalence,
      it is currently underestimated and underdiagnosed. A monitoring protocol is vital
      to the early detection of cochleotoxicity and its implementation is widely
      encouraged in every hospital unit. Our aim was to elaborate a cochleotoxicity
      monitoring protocol for patients treated with platinum compounds or
      aminoglycosides antibiotics. METHODS: PubMed(r) database was searched using terms
      relevant to drug cochleotoxicity in order to identify the most adequate protocol.
      Several articles and guidelines influenced our decision. RESULTS: There is no
      consensus on a universal monitoring protocol. Its formulation and application
      rely heavily on available resources and personnel. High-frequency audiometry and
      otoacoustic emissions play an important role on early detection of
      cochleotoxicity caused by aminoglycoside antibiotics and platinum compounds.
      CONCLUSION: A cochleotoxicity monitoring protocol consisting on an initial
      evaluation, treatment follow-up and post-treatment evaluation is proposed.

PMID- 28501267
TI  - Gender equity imbalance in electrocardiology: A call to action.
AB  - Despite the increasing number of women entering the medical profession, senior
      positions and academic productivity in many fields of medicine remain to be men
      dominated. We explored gender equity in electrocardiology as perceived by recent
      academic productivity and also active participation (presidencies and board
      constituents) in both the International Society of Electrocardiology (ISE) and
      the International Society for Holter and Noninvasive Electrocardiology (ISHNE).
      Academic productivity was measured by authorship (first and senior) in the
      Journal of Electrocardiology (JECG) and the Annals of Noninvasive
      Electrocardiology (ANE) in 2015. The percentage of women ISE and ISHNE Presidents
      was 5.6% and 0%, respectively. Current women board constituents for each society
      was 12.1% for ISE, and 9.4% for ISHNE. JECG articles published in 2015 had
      considerably less women compared to men for both senior (16.3%) and first (25.3%)
      authorship. ANE articles published in 2015 followed the same trends in gender,
      having less women compared to men for both senior (9.4%) and first (19.3%)
      authorship. There is a gender equity imbalance in the field of Electrocardiology.
      Identifying a gender imbalance is important for understanding reasons behind
      these trends, and may also help improve gender equity in Electrocardiology.

PMID- 28501268
TI  - Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way
      Stopcock Methods in Transarterial Chemoembolization for Liver Tumor.
AB  - PURPOSE: To compare physicochemical properties of emulsions of ethiodized oil
      (Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different
      techniques for conventional transarterial chemoembolization. MATERIALS AND
      METHODS: Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3
      way stopcock. The following technical parameters were compared: ratio of
      epirubicin solution to Lipiodol (1:2 vs 1:1), number of pumping exchanges through
      the stopcock (20 exchanges vs 10 exchanges), pumping speed (1 s/push vs 2
      s/push), and first push syringe (epirubicin solution vs Lipiodol). RESULTS: The
      mean percentage of water-in-oil was 70.45 +/- 1.51 in the 1:2 epirubicin-Lipiodol
      ratio and 16.03 +/- 2.95 in the 1:1 ratio (P < .001). The first push syringe did
      not influence emulsion type. Median droplet sizes were significantly larger in
      the slower pumping speed (52.0 MUm in 2 s vs 33.7 MUm in 1 s; P < .001), whereas
      there was no significant difference in number of pumping exchanges. Droplet sizes
      enlarged during 30 minutes after pumping. Viscosity was lower in the 1:1 ratio
      and the slower pumping speed. Viscosity decreased during 30 minutes after
      pumping. CONCLUSIONS: The ratio of epirubicin to Lipiodol is a significant factor
      to form water-in-oil emulsions with higher viscosity. The percentage of water-in
      oil is limited to 70% using current pumping techniques. The pumping speed
      strongly influences droplet size and viscosity.

PMID- 28501270
TI  - A novel stereotactic frame for real PET-guided biopsies: A preclinical proof-of
      concept.
AB  - PURPOSE: To design, build and test a stereotactic device that allows PET image
      guided biopsies to be performed. METHODS: An initial prototype consisting of four
      main pieces, one of which contains radioactive markers to make it visible in the
      PET images, was built using a 3D printer. Once the device is mounted, a spherical
      coordinate system is built with the entrance needle point in the skin as the
      origin of coordinates. Two in-house software programs, namely getCoord.ijm, which
      obtains the spherical coordinates of the tumour tissue to be biopsied, and
      getNeedle.ijm, which virtualizes the inner needle tip once the puncture has taken
      place, were written. This prototype was tested on an FDG-doped phantom to
      characterize both the accuracy of the system and the procedure time. RESULTS: Up
      to 11 complete biopsy procedures were conducted. The mean total procedure time
      was less than 20min, which is less than the procedure time of conventional
      standard CT-guided biopsies. The overall accuracy of the system was found to be
      5.0+/-1.3mm, which outperforms the criterion used in routine clinical practice
      when targeting tumours with a diameter of 10mm. CONCLUSIONS: A stereotactic frame
      to conduct real PET image-guided biopsies has been designed and built. A proof-of
      concept was performed to characterize the system. The procedure time and accuracy
      of the system were found to meet the current needs of physicians performing
      biopsies.

PMID- 28501269
TI  - Peak enhancement ratio of myocardium to aorta for identification of myocardial
      ischemia using dynamic myocardial computed tomography perfusion imaging.
AB  - BACKGROUND: This study aimed to evaluate the feasibility of peak enhancement (PE)
      ratio of myocardium to aorta (PER) derived from stress dynamic computed
      tomography myocardial perfusion imaging (CTP) for the detection of myocardial
      ischemia assessed by magnetic resonance (MR) imaging. METHODS: Forty-four
      patients who underwent stress dynamic CTP and MR imaging were retrospectively
      evaluated. From the time-attenuation curve, myocardial PE, PER, and myocardial
      blood flow (MBF) were calculated on a segment-based analysis. The correlation
      between myocardial and aortic PE was assessed by Spearman's correlation, and the
      differences in myocardial PE and PER between normal and ischemic myocardium were
      assessed by the Mann-Whitney U-test. The diagnostic accuracies of myocardial PE,
      PER, and MBF for detecting myocardial ischemia were compared by receiver
      operating characteristic analysis. RESULTS: Of 704 segments, 258 segments (37%)
      were diagnosed as myocardial ischemia with MR imaging. Myocardial and aortic PE
      were significantly correlated in both normal and ischemic segments (r=0.76 and
      0.58; p<0.05, in each). The myocardial PE and PER of ischemic segments were
      significantly lower than those of normal segments (p<0.05, in each). Sensitivity
      and specificity were 61% [95% confidence interval (CI), 55-70%] and 83% (95% CI,
      73-87%) for myocardial PE, 78% (67-88%) and 82% (95% CI, 70-91%) for PER, and 81%
      (95% CI, 73-87%) and 85% (95% CI, 79-92%) for MBF. There was a significantly
      larger area under the curve for PER (0.87; 95% CI, 0.84-0.90) and MBF (0.88;
      95%CI, 0.85-0.91), compared to myocardial PE (0.75; 95% CI, 0.70-0.79) (p<0.05,
      in each). There was no significant difference in area under the curve between PER
      and MBF. CONCLUSIONS: The semi-quantitative parameter of PER showed a high
      diagnostic accuracy for the detection of myocardial ischemia, comparable to that
      of MBF.

PMID- 28501271
TI  - Virtual cystoscopy, computed tomography urography and optical cystoscopy for the
      detection and follow-up for bladder cancer.
AB  - OBJECTIVES: To evaluate the utility of virtual cystoscopy (VC) performed with CT
      urography in patients being studied under gross hematuria or patients being
      followed-up after a previous bladder cancer and compare the results with those
      obtained with gold standard technique (optical cystoscopy). METHODS:
      Retrospective study of 117 patients who were referred for VC by the Urology
      Department between May 2014 and May 2015. Those patients presented with gross
      hematuria or they were previously treated patients from bladder cancer being
      followed up. These patients were evaluated with MDCT and virtual cystoscopy after
      distending the bladder with air. The results were compared with those obtained
      with optical cystoscopy which was performed no more than a week after. RESULTS:
      The global sensitivity and specificity of VC were 81,8 and 92,1%. Aditional
      findings detected in CT urography were an aortic dissection, urinary lithiasis
      and colonic metastasis. CONCLUSION: VC seems an useful technique in the diagnosis
      and follow-up for bladder cancer with a good correlation with OC. The main
      limitations are the impossibility of biopsy during the procedure and the
      detection of erythematous lesions. Collateral findings can be detected performed
      with CT urography although the high radiation exposure does not recommend their
      combined use.

PMID- 28501272
TI  - Oxidative stress in pre-eclampsia; have we been looking in the wrong place?

PMID- 28501273
TI  - Cerebral white matter lesions after pre-eclampsia.
AB  - BACKGROUND: Women who have had pre-eclampsia in their previous pregnancies
      demonstrate a greater prevalence of cerebral white matter lesions several years
      after the pregnancy than women who have been normotensive during their pregnancy.
      Both the pathophysiology and the timing of development of these lesions are
      uncertain. White matter lesions, in the general population, are associated with
      an increased risk of stroke, dementia and death. AIMS AND OBJECTIVES: The
      objective of the study was to determine the prevalence of cerebral white matter
      lesions amongst women with severe pre-eclampsia at delivery, 6months and 1year
      postpartum and to establish the possible pathophysiology and risks factors.
      METHODS: This was a longitudinal study performed at Steve Biko Academic Hospital,
      a tertiary referral hospital in Pretoria South Africa. Ninety-four women with
      severe pre-eclampsia were identified and recruited during the delivery admission.
      Magnetic resonance imaging (MRI) of the brain was performed post - delivery and
      at 6months and 1year postpartum. RESULTS: Cerebral white matter lesions were
      demonstrated in 61.7% of women at delivery, 56.4% at 6months and 47.9% at 1year.
      Majority of the lesions were found in the frontal lobes of the brain. The
      presence of lesions at 1year post-delivery was associated with the number of
      drugs needed to control blood pressure during pregnancy (OR 5.1, 95% CI 2.3-11.3,
      p<0.001). The prevalence of WMLs at 1year was double in women with chronic
      hypertension at 1year compared to those women who were normotensive (65.1% vs
      32.3%). CONCLUSION: Women who require 2 or more drugs to control blood pressure
      during pregnancy have an increased risk of developing cerebral white matter
      lesions after delivery.

PMID- 28501274
TI  - Impact of fetal growth on pregnancy outcomes in women with severe preeclampsia.
AB  - OBJECTIVE: To estimate whether pregnancy outcomes in women with severe
      preeclampsia (sPE) with small for gestational age (SGA) fetuses differ from those
      with sPE without SGA or isolated SGA. STUDY DESIGN: We conducted a retrospective
      cohort study of consecutive non-anomalous, livebirths in a single tertiary care
      institution from 2004 to 2008. We compared pregnancy outcomes in women who had
      sPE with SGA (birthweight<10th percentile), and sPE without SGA to those with
      isolated SGA as reference. The primary outcome was a neonatal composite score
      including low 5-min APGAR, NICU admission and neonatal death. Secondary outcomes
      were components of the composite as well as placental abruption and cesarean
      delivery. Analysis was repeated with SGA defined as birthweight<5th percentile.
      Multivariable logistic regression was used to adjust for confounders. RESULTS:
      1905 women met inclusion criteria: 156 sPE with SGA, 746 sPE without SGA, 1003
      isolated SGA. The risk of the neonatal composite score was higher for sPE with
      SGA (adjusted odds ratio [aOR] 2.29; 95% confidence interval [CI] 1.39-3.79) and
      sPE without SGA (aOR 3.66; 95% CI 2.71-4.93) compared to isolated SGA. The risk
      of abruption and cesarean were similarly increased in women with sPE with SGA and
      sPE without SGA compared to those with isolated SGA. CONCLUSION: Similar to women
      with sPE without SGA fetus, women who have sPE with SGA are at a higher risk for
      several adverse maternal and neonatal outcomes compared to isolated SGA. These
      findings suggest that women with preeclampsia and SGA should be managed as sPE
      rather than as isolated SGA.

PMID- 28501275
TI  - Dysregulation of the Fas/FasL system in an experimental animal model of HELLP
      syndrome.
AB  - INTRODUCTION: Placental FasL is up-regulated in women with HELLP (hemolysis
      elevated liver enzyme and low platelet) syndrome and has been proposed to
      contribute to the liver damage seen in these patients. OBJECTIVE: This study
      aimed to determine if an experimental rodent model of HELLP also had
      dysregulation of Fas/FasL compared to normal pregnant (NP) rats. We also set out
      to determine if blockade of the endothelin system regulated Fas/FasL expression
      in HELLP rats. STUDY DESIGN: On gestational day (GD) 12, sEng (7ug/kg) and sFlt-1
      (4.7ug/kg) infusion began via mini-osmotic pump into NP rats. On GD19 plasma and
      tissue were collected and FasL and Fas were measured via enzyme linked
      immunosorbent assay and gene expression via real-time PCR. RESULTS: HELLP rats
      had significantly more circulating and placental FasL compared to NP rats,
      whereas hepatic FasL was decreased and placental Fas was increased compared to NP
      rats. Administration of an endothelin A receptor antagonist (ETA) beginning on
      GD12 significantly decreased placental expression of Fas in HELLP rats. Liver
      mRNA transcript of Fas was significantly increased in HELLP rats compared to NP
      rats. CONCLUSION: These data suggest that rats in this experimental model of
      HELLP syndrome have abnormal expression of the Fas/FasL system. Future studies
      will examine the sources of Fas/FasL dysregulation in this model and if blockade
      could reduce some of the inflammation and hypertension associated with HELLP
      syndrome.

PMID- 28501276
TI  - Diagnosis of preeclampsia and fetal growth restriction with the sFlt-1/PlGF
      ratio: Diagnostic accuracy of the automated immunoassay Kryptor(r).
AB  - OBJECTIVE: We aimed to characterize the diagnostic accuracy of the Kryptor(r)
      assay for sFlt-1 and PlGF in maternal serum samples of uneventful singleton
      pregnancies and subjects with preeclampsia (PE) and PE-related outcomes such as
      fetal growth restriction (FGR). Longitudinal reference ranges of the sFlt-1 and
      PlGF level in the course of normal pregnancies were generated. METHODS: A cohort
      of subjects with PE and PE-related outcomes including FGR in the third trimester
      was compared to a cohort of women with uneventful outcome. Serum levels of sFlt
      1, PlGF level as well as the sFlt-1/PlGF ratio was analysed with the Kryptor(r)
      assay and compared between the case- and control groups. Cut-off values were
      generated and diagnostic accuracy examined. RESULTS: Longitudinal reference
      ranges of the sFlt-1 and PlGF level in healthy pregnancies were in line with
      those levels measured with other immunoassays. Comparison of the sFlt-1/PlGF
      ratio between PE-related outcomes including FGR or PE and healthy controls showed
      a high diagnostic accuracy with an area under the curve (AUC) of 0.917 for PE
      related outcomes and 0.919 for PE.

PMID- 28501277
TI  - Inherited predisposition to preeclampsia: Analysis of the Aberdeen
      intergenerational cohort.
AB  - OBJECTIVE: To assess the magnitude of familial risk of preeclampsia and
      gestational hypertension in women born of a preeclamptic pregnancy and those born
      of pregnancy complicated by gestational hypertension while accounting for other
      risk factors. METHODS: An intergenerational dataset was extracted from the
      Aberdeen Maternity and Neonatal Databank (AMND) which records all pregnancy and
      delivery details occurring in Aberdeen, Scotland since 1950. The analysis
      included all nulliparous women whose mothers' records at their births are also
      recorded in the AMND. Multinomial logistic regression was used to assess the risk
      of having preeclampsia or gestational hypertension based on maternal history of
      preeclampsia or gestational hypertension. RESULTS: There were 17302 nulliparous
      women included, of whom 1057(6.1%) had preeclampsia while 4098(23.7%) had
      gestational hypertension. Furthermore, 424(2.5%) and 2940(17.0%) had maternal
      history of preeclampsia and gestational hypertension respectively. The risk of
      preeclampsia was higher in women who were born of pregnancies complicated by
      preeclampsia (adjusted RRR 2.55 95% CI 1.87-3.47). This was higher than the risk
      observed in women whose mothers had gestational hypertension (adjusted RRR 1.44
      95% CI 1.23-1.69). Conversely, the risk of gestational hypertension was similar
      in those who were born of preeclamptic pregnancies (adjusted RRR 1.37 95% CI 1.09
      1.71) and those whose mothers had gestational hypertension (adjusted RRR 1.36 95%
      CI 1.24-1.49). CONCLUSION: There was a dose response effect in the inheritance
      pattern of preeclampsia with the highest risk in women born of preeclamptic
      pregnancies. Gestational hypertension showed similar increased risk with maternal
      gestational hypertension and preeclampsia.

PMID- 28501278
TI  - Antenatal risk factors associated with need of postpartum antihypertensives in
      women with preeclampsia in South India: Case control study.
AB  - OBJECTIVES: To investigate the antepartum risk factors associated with the need
      for antihypertensive medication in the postpartum period in women with pre
      eclampsia. METHODOLOGY: Matched retrospective case control study was done in a
      tertiary center in south India between January 2016 and June 2016. We compared
      100 preeclamptic women requiring antihypertensive medication in the postpartum
      period at discharge with 100 preeclamptic women who were not on antihypertensive
      medication at discharge, matched for age and parity at a ratio 1:1. Demographic
      data, maternal medical conditions, and delivery data were abstracted from
      maternal charts. Risk factors were evaluated using conditional logistic
      regression. RESULTS: Gestational age at delivery was comparable in both groups
      (34.3vs. 35.6weeks, p=0.220). Cesarean section rates were higher in the cases
      compared to controls (53% vs. 32%, p=0.004). After adjusting for age and parity
      women who had eclampsia, required prophylactic magnesium sulphate therapy and
      high peak antenatal systolic blood pressure were associated with postpartum
      antihypertensives. Using multivariate conditional logistic regression, mean
      systolic blood pressure (OR=1.03, 95% CI 1.00-1.07), development of eclampsia
      (OR=6.43, 95% CI 1.03-39.91) and need of prophylactic magnesium sulphate
      (OR=5.02, 95% CI 2.02-12.47) were found to be associated with the need of
      postpartum antihypertensives. CONCLUSIONS: In women with preeclampsia,
      development of eclampsia, use of prophylactic magnesium sulphate and high peak
      antenatal systolic blood pressure are more likely to require antihypertensives in
      postpartum period.

PMID- 28501280
TI  - Evaluation of placental vascularization by three-dimensional ultrasound
      examination in second and third trimester of pregnancies complicated by chronic
      hypertension, gestational hypertension or pre-eclampsia.
AB  - OBJECTIVES: The purpose of this study was to assess three-dimensional placental
      power Doppler indices in second and third trimester of pregnancies complicated by
      chronic-, gestational hypertension or pre-eclampsia. METHODS: We analyzed 226
      pregnancies prospectively measuring three-dimensional placental power Doppler
      indices (vascularization index, flow index, vascularization flow index) in cases
      of normal blood pressure (N=109), chronic hypertension (N=43), gestational
      hypertension (N=57) and pre-eclampsia (N=17). We evaluated the correlation among
      vascularization indices, flow characteristics of uterine arteries and perinatal
      outcome. We assessed the influence of maternal factors (pregestational body mass
      index, previous pregnancies/deliveries, maternal age) on vascularization indices,
      and analyzed histological findings of placenta from pregnancy hypertension
      groups. RESULTS: Vascularization index was significantly higher (p=0.010) in
      pregnancies with chronic- and lower (p=0.152) in pregnancies with gestational
      hypertension and preeclampsia compared to the normal group. Flow index was
      significantly lower in all three pathological groups compared to normal group.
      Placental volume was significantly smaller (p<0.001) in all three pathological
      groups than in normal pregnancies at the time of delivery, and there was no
      significant difference between the three affected groups. The rate of adverse
      pregnancy outcomes showed no significant difference between the normal and
      chronic hypertension groups. We observed significantly lower 1', 5' and 10' APGAR
      scores (p<0.,001), and birth weight in preeclampsia compared to chronic-,
      gestational hypertension, and normal groups. Maternal factors had no influence on
      the development of the power Doppler indices. CONCLUSION: Vascularization indices
      seem good markers for the prediction of risks and adverse outcomes in case of
      pregnancy hypertension.

PMID- 28501279
TI  - Clinical and laboratory markers in the recovery from severe preeclampsia.
AB  - OBJECTIVE: To examine the recovery from severe Preeclampsia toxemia (PET) in
      women treated with magnesium sulfate (MgSO4) during the first 24h postpartum as
      reflected by the changes in various clinical and laboratory markers. STUDY
      DESIGN: The study population included all women diagnosed with severe PET that
      gave birth at the Soroka University Medical center between 2013 and 2014, and
      were treated with MgSO4 in the first 24h postpartum. Data were collected from the
      institutional computerized records. The different parameters were examined in 6h
      intervals and were compared using appropriate statistical tests. MAIN OUTCOMES
      MEASURES: Change in various postpartum laboratory and clinical parameters.
      RESULTS: During the study period there were 132 singleton deliveries with severe
      PET treated with a 24-hours postpartum MgSO4 regimen. Most of the women were
      primigravida and delivered vaginally. Both mean systolic and mean diastolic blood
      pressure values have shown recovery to normal values after the first 6h of
      treatment (P<0.001). Urine output and proteinuria have demonstrated later
      recovery (after 12h). CONCLUSIONS: When assessing the natural recovery of severe
      PET features, the earliest parameter to recover during the first 24h postpartum
      is hypertension followed by urine output and the proteinuria. Further larger
      studies are needed in order to confirm these results. Moreover, the use of these
      parameters may allow using shorter MgSO4 treatment regimens for appropriate women
      showing earlier recovery and facilitating quicker mother-baby bonding and
      emotional recovery.

PMID- 28501281
TI  - Alteration of serum adropin level in preeclampsia.
AB  - To clarify the alterations in serum adropin and preptin concentrations in
      preeclampsia, we determined serum adropin and preptin levels in 29 women with
      normal pregnancy and 32 women with preeclampsia. We found that maternal age, body
      mass index and fetal gender were not significantly different between two groups;
      however, blood pressure, gestational age and neonatal birth weight were
      significantly different. Serum adropin levels were significantly increased in
      women with preeclampsia compared with those with normal pregnancy but there were
      no significant differences in preptin levels. An increase in maternal serum
      adropin level was found in preeclampsia, and this may be a compensation for
      pregnancy complicated with preeclampsia.

PMID- 28501282
TI  - Proteinuria in preeclampsia: Not essential to diagnosis but related to disease
      severity and fetal outcomes.
AB  - Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality
      globally and proteinuria can be one of the cardinal features of this disease.
      However, studies about the association of the amount of proteinuria and the
      severity of preeclampsia, and perinatal outcomes are limited. Data on 239 women
      with preeclampsia were retrospectively collected from a university teaching
      hospital from September 2011 to June 2013 and analysed. Data included all
      clinical parameters and proteinuria in a 24h urine collection. In cases of severe
      preeclampsia, significantly fewer patients had proteinuria levels <0.3g/L in
      comparison to any of the other groups with proteinuria >0.3g/L, but there was no
      difference in cases of severe preeclampsia when proteinuria levels were >0.3g/L.
      Furthermore, when proteinuria levels were >0.3g/L, the frequency of severe
      preeclampsia in each group was significantly higher than the frequency of mild
      pre-eclampsia cases. Time of onset was significantly earlier in patients with
      proteinuria >3g/L in a 24h urine collection, but time between the onset of
      preeclampsia and delivery was not correlated with the amount of proteinuria. The
      birth weight was significantly lower in patients with proteinuria >3g/L. The
      incidence of fetal growth restriction or stillbirth was significantly higher in
      patients with proteinuria >5g/L. Our data demonstrate that the amount of
      proteinuria is not associated with the severe of preeclampsia, once proteinuria
      is detected, but is related to the severity of preeclampsia. The adverse fetal
      outcomes appear to be the function of prematurity rather than proteinuria itself.

PMID- 28501283
TI  - Assessment of annexin A5 and annexin A2 levels as biomarkers for pre-eclampsia: A
      pilot study.
AB  - Deficient anticoagulant activity of annexin A5 and deficient profibrinolytic
      activity of annexin A2 have been linked to increased risk of thrombotic events.
      Placental dysfunction due to fibrin deposition/microthrombi has been implicated
      in the pathogenesis of pre-eclampsia (PE). In this study, we aimed to assess
      serum levels of annexin A5 and annexin A2 in a cohort of PE patients and
      investigate their role as biomarkers for the development of the disease. We
      examined 80 women in total; 40 healthy pregnant women and 40 pregnant women with
      PE after 20weeks of pregnancy. Women were subjected to full clinical assessment,
      ultrasonography, and laboratory testing including complete blood picture, liver
      and kidney function tests and assessment of serum and urine proteins. Annexin A5
      and annexin A2 were analyzed using enzyme-linked immunosorbent assay. The study
      showed serum annexin A2 but not annexin A5 was significantly reduced (P=0.029) in
      women with PE (total and severe cases) compared to those with normal pregnancy.
      The ROC analysis of annexin A2 level for the prediction of development of PE
      showed an area under the curve of 0.64 (P=0.029), and the best cut-off value was
      0.89ng/ml with a sensitivity of 70.0% and a specificity of 70.0%. Univariate
      analysis showed annexin A2 of <0.89ng/ml, proteinuria, lower platelet count and
      higher BP were associated with significantly higher risk to develop PE. Based on
      this pilot study, serum annexin A2 levels may be a useful biomarker for pre
      eclampsia. However, a larger study is required before a final conclusion is made.

PMID- 28501284
TI  - Reliability of home blood pressure monitoring devices in pregnancy.
AB  - Home blood pressure monitors are freely available and used for women during
      pregnancy. The exact role of home blood pressure monitoring in pregnancy remains
      uncertain, and few such monitors have been validated for use in pregnancy. As it
      has been our Unit's policy to test these devices against sphygmomanometry (as the
      gold standard) before clinical use for some years now, we undertook this study to
      ascertain the degree of accuracy or inaccuracy of these devices in usual clinical
      practice. We analysed 9 consecutive blood pressures (BP) alternately using an
      automated home BP device and sphygmomanometry in 127 pregnant women with
      hypertension using two different methods: a) a modified version of the British
      Hypertension Society's guidelines for analysing automated devices, and b)
      examining the difference between the mean of blood pressure readings by the
      device and sphygmomanometry for each patient. 87 devices (69%) had systolic BP
      within 5mmHg or less and 98 (77%) were within 5mmHg for diastolic BP. The
      frequency of systolic BPs within 5mmHg was similar for non-validated vs.
      validated devices (75vs. 60%; p=0.23). Similarly, diastolic BP within 5mmHg was
      similar for non-validated vs. validated devices (86vs. 68%, p=0.06). Our findings
      showed that a wide variety of devices are used and few if any have been formally
      validated for use in pregnancy. As a group the devices provide accurate BP in the
      majority of women, but up to a quarter will have a BP difference of at least
      5mmHg, and this is not related to the absolute BP. Furthermore using a home BP
      device validated for general use in non-pregnant subjects appeared as reliable as
      using other non-validated devices. On the basis of these data we recommended
      clinicians always perform their own analysis of a patient's home BP machine
      accuracy prior to home use using a simple protocol as described here, even if the
      machine has been validated for general use.

PMID- 28501285
TI  - Construct validity of a novel, objective evaluation tool for the basics of open
      laparotomy training using a simulated model.
AB  - BACKGROUND: We describe initial success in designing and implementing an
      objective evaluation for opening and closing a simulated abdomen. METHODS: (1) An
      assessment for laparotomy was created using peer-reviewed literature, texts, and
      the input of academic surgeons nationally; (2) the assessment was evaluated for
      construct validity, comparing the videotaped performance of laparotomy by
      surgical experts and novices on a viscoelastic model; and (3) the basics of open
      laparotomy training (BOLT) curriculum was piloted with junior residents to
      evaluate efficacy at improving performance. RESULTS: Experts performed better
      than novices opening (.94 vs .51; P < .001), closing (.85 vs .16; P < .001), and
      overall performance (.88 vs .27; P < .001). Novices caused bowel injury more
      frequently (5 vs 1; P < .05) and took longer to open the abdomen (6:06 vs 3:43; P
      = .01). After completing the BOLT curriculum, novices improved for opening (1.00
      vs .50; P = .014), closing (.80 vs .10; P = .014), and overall score (.87 vs .23;
      P = .014). CONCLUSIONS: We demonstrate construct validity of an evaluation tool
      for simulated laparotomy, and pilot efforts with the BOLT curriculum have shown
      promise.

PMID- 28501286
TI  - The correlation between stabbing-related upper extremity wounds and survival of
      stabbing victims with abdominal and thoracic injuries.
AB  - BACKGROUND: When treating patients with stab injuries of the torso, clinicians
      often lack timely information about the degree and nature of internal organ
      damage. An externally observable sign significantly associated with
      characteristics of torso injuries may therefore be useful for practitioners. One
      such potential sign is the presence of wounds to the hands, sometimes sustained
      during victims' attempt to defend themselves during the violent altercation.
      Thus, the primary aim of this study was to evaluate the association between
      presence of upper extremity wounds and the severity of the thoracic and intra
      abdominal injuries due to stabbing. METHODS: This study was carried out
      retrospectively using data on 8714 patients with stabbing-related injuries from
      19 trauma centers that participated in the Israeli National Trauma Registry
      (INTR) between January 1st1997 and December 31st 2013. Patients with wounds of
      upper extremities in addition to torso injuries (UE group) were compared to other
      patients with torso injuries (TO group) in terms of demographics, injury
      characteristics and clinical outcome. RESULTS: The compared groups were found to
      be homogeneous in terms of age and systolic blood pressure; the number of
      sustained torso injuries was also identical. The UE group comprised a slightly
      greater percentage of females, however both groups were predominantly male.
      Patients with upper extremity injuries had a lower proportion of internal organ
      damage (36% vs. 38.5%) and lower mortality (0.9% vs. 2%). The higher mortality of
      patients without upper extremity wounds remained significantly different even
      when adjusted by other epidemiological parameters (OR 2.46, 95% CI 1.33-5.08).The
      number of sustained upper extremity injuries was positively associated with
      deeper penetration of the torso by the stabbing instrument. CONCLUSIONS: Patients
      with stabbing-related upper extremity wounds had a significant survival advantage
      over patients without such injuries. However, a greater number of sustained upper
      extremity wounds may be an external sign of greater severity of thoracic and
      intraabdominal stabbing injuries.

PMID- 28501287
TI  - Femoral nerve block in a representative sample of elderly people with hip
      fracture: A randomised controlled trial.
AB  - INTRODUCTION: The number of elderly people with hip fracture and dementia is
      increasing, and many of these patients suffer from pain. Opioids are difficult to
      adjust and side effects are common, especially with increased age and among
      patients with dementia. Preoperative femoral nerve block is an alternative pain
      treatment. AIM: To investigate whether preoperative femoral nerve block reduced
      acute pain and opioid use after hip fracture among elderly patients, including
      those with dementia. PATIENTS AND METHODS: In this randomised controlled trial
      involving patients aged >=70years with hip fracture (trochanteric and cervical),
      including those with dementia, we compared femoral nerve block with conventional
      pain management, with opioid use if required. The primary outcome was
      preoperative pain, measured at five timepoints using a visual analogue scale
      (VAS). Preoperative opioid consumption was also registered. RESULTS: The study
      sample comprised 266 patients admitted consecutively to the Orthopaedic Ward. The
      mean age was 84.1 (+/-6.9)years, 64% of participants were women, 44% lived in
      residential care facilities, and 120 (45.1%) had dementia diagnoses. Patients
      receiving femoral nerve block had significantly lower self-rated pain scores from
      baseline to 12h after admission than did controls. Self-rated and proxy VAS pain
      scores decreased significantly in these patients from baseline to 12h compared
      with controls (p<0.001 and p=0.003, respectively). Patients receiving femoral
      nerve block required less opioids than did controls, overall (2.3+/-4.0 vs. 5.7+/
      5.2mg, p<0.001) and in the subgroup with dementia (2.1+/-3.3 vs. 5.8+/-5.0mg,
      p<0.001). CONCLUSION: Patients with hip fracture, including those with dementia,
      who received femoral nerve block had lower pain scores and required less opioids
      before surgery compared with those receiving conventional pain management.
      Femoral nerve block seems to be a feasible pain treatment for elderly people,
      including those with dementia.

PMID- 28501288
TI  - Recurrent Episodes of Brief Global Amnesia Related to Intrathecal Baclofen Pump:
      Originally Mistaken for Psychogenic Nonepileptic Seizures.

PMID- 28501289
TI  - Alcohol-Related Dementia: A Systemic Review of Epidemiological Studies.
AB  - BACKGROUND: Alcohol-related dementia (ARD) is a heterogeneous long-term cognitive
      problem that can develop in the course of alcoholism. Current understanding of
      ARD remains limited. METHODS: We conducted a systematic review to synthesize
      available data on the epidemiology of ARD, through searching the relevant studies
      in the PubMed, PsycINFO, and ALOIS. "Alcohol" and "dementia" were used as
      keywords. RESULTS: We included articles published between January 1, 1991 and
      February 29, 2016, where language was not limited. Of the 9 identified articles,
      the prevalence of ARD ranged from 1.19/1000 in multiday admission patients
      residing in the United Kingdom to 25.6% in elderly clinic alcoholics from the
      United States. The proportion of ARD in early-onset dementia taken from 3 studies
      was approximately 10%, whereas only 1.28% in late-onset dementia taken from 1
      study. CONCLUSIONS: Considering the relatively high proportion of ARD in early
      onset dementia and its potentially reversible course, future investigation into
      ARD is necessary.

PMID- 28501290
TI  - Use of Transdermal Selegiline in Pregnancy and Lactation: A Case Report.

PMID- 28501291
TI  - Use and dependence on opioid drugs in the Spanish population with chronic pain:
      Prevalence and differences according to sex.
AB  - OBJECTIVES: To analyse the prevalence in the use and dependence on opioid drugs
      in the Spanish population with chronic pain and evaluate the differences
      according to sex. PATIENTS AND METHODS: The demographic variables, opioid
      treatment characteristics and use of other substances were assessed in 229 users
      of opioid drugs. A descriptive bivariate analysis of the data was performed.
      RESULTS: Forty-six percent of the patients met the criteria of dependence on
      opioid drugs (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition
      [DSM-IV-TR]). Alcohol and cannabis consumption was greater in the men. The rates
      of dependence on the use of opioid drugs were significantly higher in the
      extended treatments. CONCLUSIONS: Planning for treatments with opioids and
      strategies for preventing inappropriate use should not depend on the patient's
      sex. We need further studies on the medical and psychological variables related
      to the use of and dependence on opioids.

PMID- 28501292
TI  - Gender Differences in Medicine-From Medical School to Medicare.

PMID- 28501293
TI  - Gender Differences in Physician Service Provision Using Medicare Claims Data.
AB  - OBJECTIVE: To determine differences in the provision of Medicare services based
      on physician gender in the United States. PATIENTS AND METHODS: Participants
      included all 2013 Medicare fee-for-service physicians and their patients, a
      population that is predominantly older than 65 years. The 2013 Medicare Provider
      Utilization and Payment Data for services rendered between January 1, 2013, and
      December 31, 2013, were combined with the 2015 Physician Compare National
      Downloadable files and 2015 Berenson-Eggers Type of Service classification files.
      Total fee-for-service Medicare payments and Healthcare Common Procedure Coding
      System procedure codes for all fee-for-service beneficiaries were aggregated
      according to physician gender, specialty, years since medical school graduation,
      and type of service classifications. RESULTS: Excluding drug reimbursement, the
      mean total Medicare payments per female physician, compared with those for male
      physicians, were 41% in surgical specialties, 72% in hospital-based specialties,
      and 55% across all specialties (P<.001). The mean overall number of unique
      beneficiary visits per female physician was 59% of that for male physicians
      (P<.001). By using the Berenson-Eggers Type of Service classification, procedures
      and other services by female physicians were of 54% lower overall average
      intensity (allowed payments/number of unique patients) compared with those of
      male physicians. These differences persisted irrespective of years since medical
      school graduation (P<.001). CONCLUSION: Female physicians had smaller average
      total Medicare payments and fewer unique beneficiary visits than male physicians
      in the care of fee-for-service Medicare beneficiaries in 2013. The differences
      persisted across specialty types and years in practice. These data can identify
      variation but cannot determine causation or explain the reasons behind gender
      differences. These findings suggest, but do not prove, that female physician
      Medicare payments are lower due to different practice patterns, consisting of
      fewer patients cared for and lower intensity of care.

PMID- 28501294
TI  - Cognitive endpoints for therapy development for neuronopathic
      mucopolysaccharidoses: Results of a consensus procedure.
AB  - The design and conduct of clinical studies to evaluate the effects of novel
      therapies on central nervous system manifestations in children with neuronopathic
      mucopolysaccharidoses is challenging. Owing to the rarity of these disorders,
      multinational studies are often needed to recruit enough patients to provide
      meaningful data and statistical power. This can make the consistent collection of
      reliable data across study sites difficult. To address these challenges, an
      International MPS Consensus Conference for Cognitive Endpoints was convened to
      discuss approaches for evaluating cognitive and adaptive function in patients
      with mucopolysaccharidoses. The goal was to develop a consensus on best practice
      for the design and conduct of clinical studies investigating novel therapies for
      these conditions, with particular focus on the most appropriate outcome measures
      for cognitive function and adaptive behavior. The outcomes from the consensus
      panel discussion are reported here.

PMID- 28501295
TI  - Discovering DNA methylation patterns for long non-coding RNAs associated with
      cancer subtypes.
AB  - Despite growing evidence demonstrates that the long non-coding ribonucleic acids
      (lncRNAs) are critical modulators for cancers, the knowledge about the DNA
      methylation patterns of lncRNAs is quite limited. We develop a systematic
      analysis pipeline to discover DNA methylation patterns for lncRNAs across
      multiple cancer subtypes from probe, gene and network levels. By using The Cancer
      Genome Atlas (TCGA) breast cancer methylation data, the pipeline discovers
      various DNA methylation patterns for lncRNAs across four major subtypes such as
      luminal A, luminal B, her2-enriched as well as basal-like. On the probe and gene
      level, we find that both differentially methylated probes and lncRNAs are subtype
      specific, while the lncRNAs are not as specific as probes. On the network level,
      the pipeline constructs differential co-methylation lncRNA network for each
      subtype. Then, it identifies both subtype specific and common lncRNA modules by
      simultaneously analyzing multiple networks. We show that the lncRNAs in subtype
      specific and common modules differ greatly in terms of topological structure,
      sequence conservation as well as expression. Furthermore, the subtype specific
      lncRNA modules serve as biomarkers to improve significantly the accuracy of
      breast cancer subtypes prediction. Finally, the common lncRNA modules associate
      with survival time of patients, which is critical for cancer therapy.

PMID- 28501297
TI  - Are sensitized patients better off with a desensitization transplant or waiting
      on dialysis?
AB  - Sensitization to human leukocyte antigens (HLAs) remains one of the major
      clinical challenges for successful kidney transplantation. Two large
      observational studies have recently addressed the question of whether individuals
      are better off with a desensitization treatment followed by HLA-incompatible
      living donor transplantation or waiting on the deceased donor kidney transplant
      list for a compatible transplant. The conflicting results of these 2 studies
      largely reflect differences in the study design and study population, leaving
      clinicians to make decisions about desensitization based largely on local
      expertise and anticipated waiting times for a compatible deceased donor
      transplant.

PMID- 28501298
TI  - ACE2 as therapy for glomerular disease: the devil is in the detail.
AB  - Angiotensin-converting enzyme 2 cleaves angiotensin (Ang) II to Ang(1-7), which
      antagonizes the deleterious effects of Ang II. In this issue, 2 groups
      administered angiotensin-converting enzyme 2 in murine models of kidney disease.
      Angiotensin-converting enzyme 2 did not improve glomerular injury in 2 models of
      mild diabetic nephropathy but was partially protective in an Alport syndrome
      model. These discrepant findings may be explained by the inability of angiotensin
      converting enzyme 2 to reach the urinary space in the absence of severe
      proteinuria.

PMID- 28501299
TI  - Severe hypertension with renal thrombotic microangiopathy: what happened to the
      usual suspect?
AB  - Patients with atypical hemolytic uremic syndrome (aHUS) and malignant
      hypertension can both present with concomitant hypertension and thrombotic
      microangiopathy (TMA), rendering policy decisions complex. Timmermans et al.
      report that patients with severe hypertension and renal TMA might have
      unrecognized aHUS with underlying complement abnormalities. Based on this, they
      assert that all patients presenting with severe hypertension and renal TMA should
      be evaluated for aHUS. It remains uncertain whether this holds equally true for
      patients with malignant hypertension and renal TMA.

PMID- 28501300
TI  - A metabolite-GWAS (mGWAS) approach to unveil chronic kidney disease progression.
AB  - In this issue, McMahon et al. report that, by combining phenotypic, metabolomic,
      and genetic data, they could better detect chronic kidney disease at the early
      stages and provide insight into its pathobiology. The most significant findings
      of the study are that several urinary metabolites (e.g., glycine and histidine)
      were identified as early risk factors for chronic kidney disease, and metabolites
      with genomewide association study analysis identified associations of urinary
      metabolites (i.e., lysine and NG-monomethyl-l-arginine) with single-nucleotide
      polymorphisms of SLC7A9.

PMID- 28501301
TI  - Osteocyte dysfunction and renal osteodystrophy: not just calcium and phosphorus
      anymore.
AB  - In an important new cross-sectional analysis in this issue, Graciolli and
      colleagues present bone data from 148 adult patients across the spectrum of
      chronic kidney disease that confirm that disrupted osteocyte function and
      abnormal bone histology characterize all stages of chronic kidney disease and
      suggest that osteocytic Wnt signaling and osteocyte maturation may play a role in
      the pathogenesis of renal osteodystrophy. These concepts may alter how the
      skeletal, cardiovascular, and infectious complications of chronic kidney disease
      are managed.

PMID- 28501302
TI  - Measuring the patient response to dialysis therapy: hemodiafiltration and
      clinical trials.
AB  - There is a strong biological plausibility for benefit from removal of larger
      uremic toxins and increasing positive clinical experience with hemodiafiltration.
      However, evidence supporting hemodiafiltration is not definitive with studies
      that are often limited by serious methodological shortcomings. Morena et al. show
      that hemodiafiltration may prevent intradialytic hypotension, albeit in a study
      that also has some shortcomings. Ongoing research for hemodiafiltration is still
      needed through high-quality clinical trials that adhere to standards for clinical
      trial conduct and reporting.

PMID- 28501303
TI  - Potential relevance of shear stress for slit diaphragm and podocyte function.
AB  - Filtrate flow through the glomerular barrier produces shear stresses that tend to
      disconnect podocytes from the glomerular basement membrane. Forces are highest
      within the filtration slits. The slit diaphragm mechanically balances the lateral
      components of the shear stresses on opposing foot processes, preventing widening
      of the slit.

PMID- 28501304
TI  - Speculations on salt and the genesis of arterial hypertension.
AB  - Blood pressure salt sensitivity and salt resistance are mechanistically
      imperfectly explained. A prescient systems medicine approach by Guyton and
      colleagues-more than 50 years ago-suggested how salt intake might influence blood
      pressure. They proposed that a high-salt diet engenders sodium accumulation,
      volume expansion, cardiac output adjustments, and then autoregulation for flow
      maintenance. The autoregulation in all vascular beds increases systemic vascular
      resistance, causing the kidneys to excrete more salt and water, thus reducing
      systems to normal and minimizing any changes in blood pressure. This schema,
      which is remarkably all encompassing, included all regulatory mechanisms Guyton
      could identify at the time. Guyton introduced the idea that the kidney is
      central, particularly concerning the regulation of renal pressure natriuresis.
      Numerous criticisms have been subsequently raised, particularly recently. Kurtz
      and colleagues argue that the ability of individuals to respond with an
      appropriate vasodilatory response to increased salt intake is pivotal. Data exist
      to address that issue. Salt-resistant hypertensive models provide additional
      information. We identified a mendelian form of hypertension not related to sodium
      reabsorption in the distal nephron. The hypertension develops because of
      increased systemic vascular resistance. In addition, we rediscovered a third salt
      storage glycose-aminoglycan-related compartment, largely in the skin. This
      compartment operates independently of renal function, and when perturbed, is
      associated with salt sensitivity. More recently, we found novel molecular
      mechanisms demonstrating how large salt quantities are excreted by the kidneys
      with minimal water losses. We introduce novel interpretations as to how the
      kidneys excrete salt when the intake is high. The findings could have relevance
      as to how blood pressure may be regulated at varying salt intakes. Our purposes
      are to provide the readership with a banquet of thoughts to digest, to pursue
      Guyton's ideas, and to adjust them accordingly.

PMID- 28501305
TI  - Modeling citrate excretion.

PMID- 28501306
TI  - The Authors Reply.

PMID- 28501307
TI  - Modeling amount of acid.

PMID- 28501308
TI  - The Authors Reply.

PMID- 28501309
TI  - Hematuria from urinary ascariasis.

PMID- 28501311
TI  - The Case | An unusual case of recurrent hypokalemic periodic paralysis.

PMID- 28501310
TI  - Magnetic resonance lymphangiography in recurrent chylous ascites and chyluria.

PMID- 28501313
TI  - Corrigendum to "Believe it or not: Moving non-biological stimuli believed to have
      human origin can be represented as human movement" [Cognition 146 (2016) 431
      438].

PMID- 28501312
TI  - Preschoolers' social experiences and empathy-based responding relate to their
      fair resource allocation.
AB  - Although the development of fairness has become a topic of wide interest, little
      is known about the correlates and factors that relate to the early ontogeny of
      fairness-related decision making in preschoolers. The current study assessed 5
      year-old children's consideration of existing inequalities in their resource
      allocation decisions, that is, their tendency to allocate more resources to poor
      others than to rich others. In addition, children's prosocial responding toward
      others in pain, the amount of their social interaction experiences, and their
      social-cognitive abilities were assessed. The results provide evidence that
      children's early social interaction experiences and empathy-based prosocial
      responding relate to their fairness-related decision making, supporting a
      relational systems approach to early prosocial and moral development.

PMID- 28501314
TI  - An Introduction to the Special Issue.

PMID- 28501315
TI  - Endovascular stenting for end-stage lung cancer patients with superior vena cava
      syndrome post first-line treatments - A single-center experience and literature
      review.
AB  - BACKGROUND: Superior vena cava (SVC) syndrome is a major complication that occurs
      when a growing lung malignancy compresses the SVC extrinsically. Current
      treatment options include radiotherapy or chemotherapy to shrink the tumor or
      endovascular stenting of the SVC to restore flow. Herein, we report a case series
      treated in a single institution to demonstrate the safety, effectiveness, and
      outcomes of salvage and primary stenting for malignant SVC obstruction. METHODS:
      A total of 12 male patients with malignant superior vena cava obstruction caused
      by lung cancer underwent SVC stenting from October 2009 to May 2015. Data were
      reviewed retrospectively, including demographic and clinical characteristics,
      procedural details, and outcomes. RESULTS: Seven patients had received
      radiotherapy prior to SVC stenting, while the other five patients received
      stenting as first-line therapy for SVC syndrome. Only one patient experienced
      initial symptomatic improvement after radiotherapy, and symptoms of SVC syndrome
      recurred one year later. Wallstents(r) (Boston Scientific, Natick MA, USA) were
      used in all patients. Preoperatively, the mean narrowest SVC diameter measured by
      CT was 2.16 mm (0-5.5 mm). Technical success was achieved in all patients without
      complications such as pulmonary embolism, rupture or bleeding. Postoperative mean
      narrowest SVC diameter measured by CT during follow-up was 11.17 mm (8-13.5 mm).
      Symptoms of SVC syndrome such as arm and face swelling and dyspnea improved
      within 1-5 days in all patients. After median follow-up duration of 11.5 months,
      only one patient presented recurrent SVC syndrome due to in-stent thrombosis two
      months after stenting. CONCLUSION: Salvage SVC stenting remains a safe and
      effective treatment for patients with SVC obstruction after failure of
      radiotherapy and chemotherapy. Primary stenting may be considered at initial
      presentation of SVC syndrome to improve patients' quality of life.

PMID- 28501316
TI  - Early initiation of GnRH antagonist administration in a flexible protocol: Is it
      better?

PMID- 28501317
TI  - [Frequent users and return visits].

PMID- 28501319
TI  - Association of pyrethroids exposure with onset of puberty in Chinese girls.
AB  - Pyrethroids, a class of ubiquitous insecticides, have been considered as
      endocrine-disrupting chemicals (EDCs). Female animal studies suggested that early
      life pyrethroids exposure might delay puberty onset. However, it remains unclear
      whether this association applies to human populations. A total of 305 girls at
      the ages of 9-15 years old were recruited in Hangzhou, China in this study. The
      concentration of the common metabolite of pyrethroids, 3-phenoxybenzoic acid (3
      PBA), was analyzed in urine samples to reflect the exposure level of pyrethroids.
      The associations of 3-PBA with pubertal stages were evaluated using a multinomial
      logistic regression model. The geometric mean level of 3-PBA was 1.11 MUg/L (1.42
      MUg/g for creatinine-adjusted concentration). There was a significant 45%
      reduction in odds of being in breast stage 3 (B3) per one-unit increase in the
      log-transformed 3-PBA levels [OR = 0.55 (95%CI: 0.31-0.98), p = 0.042]. A similar
      negative association was found between urinary 3-PBA levels with later onset by
      pubic hair stage 2 (P2) [OR = 0.56 (95%CI: 0.36-0.90), p = 0.015]. Similar
      negative association was also observed between urinary 3-PBA levels and pubertal
      onset indicated by menarche [OR = 0.51 (95%CI: 0.28-0.93), p = 0.029]. For the
      first time to our knowledge, this work reveals that pyrethroids exposure may
      increase the risk of delayed pubertal onset in girls.

PMID- 28501320
TI  - Different impacts of bariatric surgical procedures on dyslipidemia: a registry
      based analysis.

PMID- 28501318
TI  - Mortality, rehospitalization, and post-transplant complications in gender
      mismatched heart transplant recipients.
AB  - BACKGROUND: Limited research has been published on outcomes in heart transplant
      (HT) recipients with gender-mismatched donors. OBJECTIVE: Compare 3-year post
      transplant outcomes in 2 groups of gender-mismatched HT recipients and a no
      mismatch group. METHODS: Sample: 347 HT recipients: 21.3% (74) received a heart
      from the opposite gender: Group 1: same gender donor/recipient (273, 78.7%);
      Group 2: female donor/male recipient (40, 11.5%); Group 3: male donor/female
      recipient (34, 9.8%). OUTCOMES: mortality, hospitalization, and complications.
      RESULTS: Female patients with male heart donors had shorter 3-year survival, were
      rehospitalized more days after HT discharge, and had more treated acute rejection
      episodes and cardiac allograft vasculopathy. No differences were found in: HT
      length of stay, respiratory failure, stroke, cancer, renal dysfunction, steroid
      induced diabetes, number of IV-treated infections, or the timing of infection and
      rejection. CONCLUSION: Female HT recipients with male donors had worse 3-year
      outcomes as compared to male-mismatch and no-mismatch groups.

PMID- 28501321
TI  - The effect of close postoperative follow-up on co-morbidity improvement after
      bariatric surgery.
AB  - BACKGROUND: Patients undergoing gastric bypass (RYGB) surgery require follow-up
      for efficacy assessment, early detection of postoperative complications, and also
      for management of co-morbid conditions. Recent literature shows support for
      improved long-term weight loss with close patient follow-up. However, attrition
      rates after RYGB have been reported as high as 50%. OBJECTIVE: The objective of
      this study was to assess the relationship between complete follow-up and
      improvement or remission of co-morbid conditions at 12 months after surgery.
      SETTING: University Hospital, United States. METHODS: Using the Bariatric
      Outcomes Longitudinal Database (BOLD) data set, patients with 12-month follow-up
      after RYGB were identified. Patients with complete follow-up were compared with
      patients who had missed either or both of their 3- and 6-month visits.
      Improvement and remission of type 2 diabetes, hypertension, and dyslipidemia were
      evaluated at 12-month postoperatively. RESULTS: 46,381 patients (30.6% of all
      RYGB patients) were identified that had follow-up with minimum 12-month data.
      Complete follow-up was recorded for 75.6% of this group with 12-month data. Of
      the 18,629 patients with type 2 diabetes at baseline, 13,498 (72.4%) and 11,287
      (60.6%) had improvement and remission, respectively, at 12 months. Improvement in
      hypertension and dyslipidemia was noted in 17,808 (62.8%) and 11,602 (55.2%) of
      patients, while 13,024 (45.9%) and 9119 (43.4%) had hypertension and dyslipidemia
      remission, respectively. After adjusting for baseline characteristics, complete
      follow-up in the first year after RYGB was independently associated with a higher
      rate of improvement or remission of co-morbid conditions. CONCLUSION: Complete
      postoperative follow-up resulted in a higher rate of co-morbidity improvement and
      remission compared with incomplete postoperative care. Patients and practices
      should strive to achieve complete and long-term follow-up after RYGB surgery.

PMID- 28501322
TI  - Extra costs of living with a disability: A review and agenda for research.
AB  - BACKGROUND: There has been a growing interest in disability and poverty on the
      international research and policy stages. Poverty assessments for persons with
      disabilities may be affected by the experience of extra costs associated with a
      disability. OBJECTIVE: This article provides a systematized review of the global
      literature on the direct costs associated with living with a disability at the
      individual or household level. METHODS: We searched three databases for peer
      reviewed journal articles that estimated extra costs associated with disability:
      Econlit, SocIndex and PubMed. RESULTS: We found 20 such studies conducted in 10
      countries. These studies were predominantly from high-income countries. Although
      studies were heterogeneous (e.g., in terms of disability measures and cost
      methodologies), estimated costs were sizeable and some patterns were consistent
      across studies. Costs varied according to the severity of disability, life cycle
      and household composition. Highest costs were observed among persons with severe
      disabilities, and among persons with disabilities living alone or in small sized
      households. CONCLUSIONS: More quantitative evidence is needed using rigorous
      methods, for instance evidence based on longitudinal data and as part of policy
      evaluations. More internationally comparable data on disability is required for
      the quantitative evidence to develop, especially in low- and middle-income
      countries where studies are scarce. Qualitative and participatory research is
      also needed, especially to investigate unmet needs, and the consequences of extra
      costs.

PMID- 28501323
TI  - Reliable and practical methods for cryopreservation of embryogenic cultures and
      cold storage of somatic embryos of Norway spruce.
AB  - Somatic embryogenesis (SE) is considered as the most-effective method for
      vegetative propagation of Norway spruce (Picea abies L. Karst). For mass
      propagation, a cryopreservation method able to handle large numbers of
      embryogenic tissues (ETs) reliably and at low costs is needed. The aim of the
      present study was to compare pretreatments, cryoprotectants and slow-cooling
      devices for cryopreservation of Norway spruce ETs, with 12 variations of methods
      and a total of 136 spruce genotypes. Secondly, possible applications for cold
      storage of mature somatic embryos were studied with the aim of developing a
      flexible time window for embling production. At best, 100% of the embryogenic
      lines were recovered following cryopreservation, but the results varied among the
      sets of lines. Also physiological condition of the tissues, pre-treatment and
      cryoprotectant applied, as well as the slow-cooling device used were found to
      affect the recovery. The best option for cryopreservation of Norway spruce is to
      select fresh growth from young ETs as samples, pretreat them on semi-solid medium
      with increasing sucrose concentration (0.1 M for 24 h; 0.2 M for another 24 h),
      apply a mixture of polyethylene glycol 6000, glucose, and dimethylsulfoxide, 10%
      w/v each, as cryoprotectant and use a programmable freezer with a slow cooling
      rate (0.17  degrees C/min). On average, 87% of the genotypes can be recovered,
      without any effect on their genetic fidelity, as shown by microsatellite markers
      and embryo production capacity. Mature somatic embryos of Norway spruce can also
      be safely cold-stored at +4  degrees C, without adverse effects on their
      germination ability.

PMID- 28501324
TI  - Using a new plateau hyperbaric chamber to alleviate high altitude hypoxia: Rabbit
      and human studies.
AB  - OBJECTIVES: To validate the effects of the new plateau hyperbaric chamber on
      alleviating high altitude hypoxia on Mount Kun Lun. METHODS: A prospective,
      controlled study of rabbits and adult volunteers was conducted at altitudes of
      355, 2880 and 4532m. We obtained arterial blood samples from rabbits and
      volunteers before and after hyperbaric treatment. The respiratory rate, heart
      rate, and blood pressure (BP) of adult volunteers were monitored during
      hyperbaric treatment. RESULTS: The mean PaO2 levels of experimental group rabbits
      and volunteers increased significantly after 60min of hyperbaric treatment at
      350, 2880 and 4532m. The mean PaCO2 and pH levels of rabbits were not significant
      different before and after hyperbaric treatment at each altitude. The mean PaCO2
      and pH levels were not significant different at 355m in the human study. However,
      at 2880 and 4532m, pH fell with increasing PaCO2 levels in humans before and
      after hyperbaric treatment. CONCLUSIONS: The new multiplace plateau hyperbaric
      chamber may be used to alleviate plateau hypoxia by increasing patient PaO2.
      However, its value in treating AMS must be confirmed in field conditions.

PMID- 28501325
TI  - A role for NMDAR-dependent cerebellar plasticity in adaptive control of saccades
      in humans.
AB  - BACKGROUND: Saccade pulse amplitude adaptation is mediated by the dorsal
      cerebellar vermis and fastigial nucleus. Long-term depression at the parallel
      fibre-Purkinjie cell synapses has been suggested to provide a cellular mechanism
      for the corresponding learning process. The mechanisms and sites of this
      plasticity, however, are still debated. OBJECTIVE: To test the role of cerebellar
      plasticity phenomena on adaptive saccade control. METHODS: We evaluated the
      effect of continuous theta burst stimulation (cTBS) over the posterior vermis on
      saccade amplitude adaptation and spontaneous recovery of the initial response. To
      further identify the substrate of synaptic plasticity responsible for the
      observed adaptation impairment, subjects were pre-treated with memantine, an N
      methyl-d-aspartate receptor (NMDAR) antagonist. RESULTS: Amplitude adaptation was
      altered by cTBS, suggesting that cTBS interferes with cerebellar plasticity
      involved in saccade adaptation. Amplitude adaptation and spontaneous recovery
      were not affected by cTBS when recordings were preceded by memantine
      administration. CONCLUSION: The effects of cTBS are NMDAR-dependent and are
      likely to involve long-term potentiation or long-term depression at specific
      synaptic connections of the granular and molecular layer, which could effectively
      take part in cerebellar motor learning.

PMID- 28501326
TI  - Management of Platelet Disorders and Platelet Transfusions in ICU Patients.
AB  - Thrombocytopenia or receipt of antiplatelet drugs, with or without bleeding, is a
      common indication for platelet transfusions in the ICU. However, there is almost
      no evidence base for these practices other than expert opinion. Also common is
      use of platelet transfusions prior to invasive procedures or surgery in patients
      with thrombocytopenia. Likewise, there is no high-quality evidence that such
      practices are efficacious or safe. Recently, it has become clear that, whether
      causal or not, patients receiving prophylactic platelet transfusions experience
      high rates of nosocomial infection, thrombosis, organ failure, and mortality,
      which increase the urgency and need for randomized trials to assess these
      practices. Investigational methods of improving the safety and efficacy of
      platelet transfusions include use of alternate strategies such as
      antifibrinolytics; use of ABO-identical, leukoreduced, and washed platelet
      transfusions; and improved storage solutions.

PMID- 28501327
TI  - Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear
      Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast
      Magnetic Resonance Imaging.
AB  - Measurement of hemodynamic wall shear stress (WSS) is important in investigating
      the role of WSS in the initiation and progression of atherosclerosis. Echo
      particle image velocimetry (echo PIV) is a novel ultrasound-based technique for
      measuring WSS in vivo that has previously been validated in vitro using the
      standard optical PIV technique. We evaluated the repeatability and
      reproducibility of echo PIV for measuring WSS in the human common carotid artery.
      We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56
      +/- 12 y). Echo PIV was highly repeatable, with an intra-observer variability of
      1.0 +/- 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5
      dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was
      reproducible, with a low inter-observer variability (max: 2.0 +/- 0.2 dyn/cm2,
      mean: 1.3 +/- 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter
      scan (test-retest) variability (max: 7.1 +/- 2.3 dyn/cm2, mean: 2.9 +/- 0.4
      dyn/cm2, min: 1.5 +/- 0.1 dyn/cm2). We compared echo PIV with the reference
      method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS
      measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p < 0.05).
      Significant differences were observed in some WSS measurements (echo PIV vs. PC
      MRI): WSS at peak systole: 21 +/- 7.0 dyn/cm2 vs. 15 +/- 5.0 dyn/cm2; time
      averaged WSS: 8.9 +/- 3.0 dyn/cm2 vs. 7.1 +/- 3.0 dyn/cm2 (p < 0.05); WSS at end
      diastole: 3.8 +/- 2.8 dyn/cm2 vs. 3.9 +/- 2 dyn/cm2 (p > 0.05). For the first
      time, we report that echo PIV can measure WSS with good repeatability and
      reproducibility in adult humans with a broad age range. Echo PIV is feasible in
      humans and offers an easy-to-use, ultrasound-based, quantitative technique for
      measuring WSS in vivo in humans with good repeatability and reproducibility.

PMID- 28501328
TI  - Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer.
AB  - OBJECTIVE: Ovarian clear cell carcinoma (OCCC) and high grade serous ovarian
      cancer (HGSOC) are associated with the highest risk of VTE among patients with
      epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane
      glycoprotein which can trigger thrombosis. We sought to evaluate if there is an
      association between VTE and tumor expression of tissue factor (TF), plasma TF,
      and microvesicle TF (MV TF) activity in this high-risk population. METHODS: We
      performed a case-control study of OCCC and HGSOC patients with and without VTE.
      105 patients who underwent surgery at a tertiary care center between January 1995
      and October 2013 were included. Plasma TF was measured with an enzyme-linked
      immunosorbent assay. A TF-dependent Factor Xa generation assay was used to
      measure MV TF activity. Immunohistochemical (IHC) analysis was performed to
      evaluate tumor expression of TF. RESULTS: 35 women with OCCC or HGSOC diagnosed
      with VTE within 9months of surgery were included in the case group. Those with
      VTE had a worse OS, p<0.0001, with a greater than three-fold increase in risk of
      death, HR 3.33 (CI 1.75-6.35). There was no significant difference in median
      plasma TF level or MV TF activity level between patients with and without VTE.
      OCCC patients had greater expression of TF in their tumors than patients with
      HGSOC, p<0.0001. CONCLUSIONS: TFMV activity and plasma TF level were not
      predictive of VTE in this patient population. Given the extensive expression of
      TF in OCCC tumors, it is unlikely IHC expression will be useful in risk
      stratification for VTE in this population.

PMID- 28501329
TI  - Eukaryotic DNA replication: Orchestrated action of multi-subunit protein
      complexes.
AB  - Genome duplication is an essential process to preserve genetic information
      between generations. The eukaryotic cell cycle is composed of functionally
      distinct phases: G1, S, G2, and M. One of the key replicative proteins that
      participate at every stage of DNA replication is the Mcm2-7 complex, a
      replicative helicase. In the G1 phase, inactive Mcm2-7 complexes are loaded on
      the replication origins by replication-initiator proteins, ORC and Cdc6. Two
      kinases, S-CDK and DDK, convert the inactive origin-loaded Mcm2-7 complex to an
      active helicase, the CMG complex in the S phase. The activated CMG complex begins
      DNA unwinding and recruits enzymes essential for DNA synthesis to assemble a
      replisome at the replication fork. After completion of DNA synthesis, the
      inactive CMG complex on the replicated DNA is removed from chromatin to terminate
      DNA replication. In this review, we will discuss the structure, function, and
      regulation of the molecular machines involved in each step of DNA replication.

PMID- 28501331
TI  - The expression of keratin 6 is regulated by the activation of the ERK1/2 pathway
      in arsenite transformed human urothelial cells.
AB  - Urothelial cancers have an environmental etiological component, and previous
      studies from our laboratory have shown that arsenite (As+3) can cause the
      malignant transformation of the immortalized urothelial cells (UROtsa), leading
      to the expression of keratin 6 (KRT6). The expression of KRT6 in the parent
      UROtsa cells can be induced by the addition of epidermal growth factor (EGF).
      Tumors formed by these transformed cells have focal areas of squamous
      differentiation that express KRT6. The goal of this study was to investigate the
      mechanism involved in the upregulation of KRT6 in urothelial cancers and to
      validate that the As+3-transformed UROtsa cells are a model of urothelial cancer.
      The results obtained showed that the parent and the As+3-transformed UROtsa cells
      express EGFR which is phosphorylated with the addition of epidermal growth factor
      (EGF) resulting in an increased expression of KRT6. Inhibition of the
      extracellular-signal regulated kinases (ERK1/2) pathway by the addition of the
      mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 kinase inhibitor U0126
      resulted in a decrease in the phosphorylation of ERK1/2 and a reduced expression
      of KRT6. Immuno-histochemical analysis of the tumors generated by the As+3
      transformed isolates expressed EGFR and tumors formed by two of the transformed
      isolates expressed the phosphorylated form of EGFR. These results show that the
      expression of KRT6 is regulated at least in part by the ERK1/2 pathway and that
      the As+3-transformed human urothelial cells have the potential to serve as a
      valid model to study urothelial carcinomas.

PMID- 28501330
TI  - Virus entry and replication in the brain precedes blood-brain barrier disruption
      during intranasal alphavirus infection.
AB  - Viral infections of the central nervous system (CNS) are often associated with
      blood-brain barrier (BBB) disruption, yet the impact of virus replication and
      immune cell recruitment on BBB integrity are incompletely understood. Using two
      photon microscopy, we demonstrate that Venezuelan equine encephalitis virus
      (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation
      within the 5' UTR that is associated with increased sensitivity to type I
      interferons (IFNs), does not directly impact BBB permeability. Following
      intranasal infection of both wild-type and IFN-induced protein with
      tetratricopeptide repeats 1 (IFIT1)-deficient mice, which fail to block TC83
      specific RNA translation, virus spreads to the olfactory bulb and cortex via
      migration along axonal tracts of neurons originating from the olfactory
      neuroepithelium. Global dissemination of virus in the CNS by 2days post-infection
      (dpi) was associated with increased BBB permeability in the olfactory bulb, but
      not in the cortex or hindbrain, where permeability only increased after the
      recruitment of CX3CR1+ and CCR2+ mononuclear cells on 6 dpi, which corresponded
      with tight junction loss and claudin 5 redistribution. Importantly, despite
      higher levels of viral replication, similar results were obtained in IFIT1
      deficient mice. These findings indicate that TC83 gains CNS access via
      anterograde axonal migration without directly altering BBB function and that
      mononuclear and endothelial cell interactions may underlie BBB disruption during
      alphavirus encephalitis.

PMID- 28501333
TI  - Comparative effectiveness of faecal microbiota transplant by route of
      administration.
AB  - The optimal route of delivery for faecal microbiota transplant (FMT) is unknown.
      This observational single-centre study analysed the two-week cure rates for all
      patients who received FMT from 2013 to 2016 according to route of delivery.
      Overall, nasogastric delivery of FMT was less effective than lower endoscopic
      delivery. When patients were stratified by illness severity, nasogastric delivery
      achieved similar cure rates in healthier individuals, whereas lower endoscopic
      delivery was preferred for relatively ill individuals. Nasogastric delivery may
      be less effective than lower endoscopic delivery; however, when taking the cost,
      preparation and potential risk into account, this difference may not be
      clinically significant for patients with mild disease.

PMID- 28501332
TI  - Inhibition of nicotinamide phosphoribosyltransferase and depletion of
      nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of
      oral squamous cell carcinoma.
AB  - Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase
      (NAMPT) expression is associated with the development and prognosis of many
      cancers, but it remains unknown regarding its role in oral squamous cell
      carcinoma (OSCC). In the present study, the results from tissue microarray showed
      that NAMPT was overexpressed in OSCC patients and its expression level was
      directly correlated with differential grades of cancer. Interestingly, treatment
      of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels
      of NAMPT protein and increased cellular death in an ATO dose- and time-dependent
      manner. Most importantly, combination of low concentration ATO with FK866 (a
      NAMPT inhibitor) exerted enhanced inhibitive effect on NAMPT protein and mRNA
      expressions, leading to synergistic cytotoxicity on cancer cells through
      increasing cell apoptosis and depleting intracellular nicotinamide adenine
      dinucleotide levels. These findings demonstrate the crucial role of NAMPT in the
      prognosis of OSCC and reveal inhibition of NAMPT as a novel mechanism of ATO in
      suppressing cancer cell growth. Our results suggest that ATO can significantly
      enhance therapeutic efficacy of NAMPT inhibitor, and combined treatment may be a
      novel and effective therapeutic strategy for OSCC patients.

PMID- 28501335
TI  - Obtaining of granular fertilizers based on ashes from combustion of waste
      residues and ground bones using phosphorous solubilization by bacteria Bacillus
      megaterium.
AB  - The article presents research results on obtaining phosphorus granulated
      fertilizers on the basis of microbiologically activated sewage sludge ashes,
      ground bones and dried blood from meat industry. Granulation tests were carried
      out using a laboratory pan granulator as well as on an experimental pilot plant.
      The aim of the studies was to select the proper composition of the mixture of raw
      materials and binding agents to obtain granulated fertilizers from waste
      materials such as MSSA and MBM and bacteria lyophilisate. Obtained fertilizer
      samples were subjected to physical tests (granulation tests etc.) and quality
      assessment. The tests confirmed that it was possible to produce granulated
      phosphate fertilizers using the Bacillus megaterium for solubilization of
      phosphorus in a simple process.

PMID- 28501334
TI  - Exchangeable Sodium Percentage decrease in saline sodic soil after Basic Oxygen
      Furnace Slag application in a lysimeter trial.
AB  - The Basic Oxygen Furnace Slag results from the conversion of hot metal into
      steel. Some properties of this slag, such as the high pH or calcium and magnesium
      content, makes it suitable for agricultural use as a soil amendment. Slag
      application to agricultural soils is allowed in some European countries, but to
      date there is no common regulation in the European Union. In Italy soils in
      coastal areas are often affected by excess sodium, which has several detrimental
      effects on the soil structure and crop production. In this study, carried out
      within an European project, the ability of the Basic Oxygen Furnace Slag to
      decrease the soil Exchangeable Sodium Percentage of a sodic soil was evaluated. A
      three-year lysimeter trial with wheat and tomato crops was carried out to assess
      the effects of two slag doses (D1, 3.5 g kg-1year-1 and D, 2, 7 g kg-1year-1) on
      exchangeable cations in comparison with unamended soil. In addition, the
      accumulation in the topsoil of vanadium and chromium, the two main trace metals
      present in the Basic Oxygen Furnace Slag, was assessed. After two years, the soil
      Exchangeable Sodium Percentage was reduced by 40% in D1 and 45% in D2 compared to
      the control. A concomitant increase in exchangeable bivalent cations (Ca++ and
      Mg++) was observed. We concluded that bivalent cations supplied with the slag
      competed with sodium for the sorption sites in the soil. The slag treatments also
      had a positive effect on tomato yields, which were higher than the control.
      Conversely the wheat yield was lower in the slag-amended soil, possibly because
      of the toxicity of vanadium added with the slag. This study showed that Basic
      Oxygen Furnace Slag decreased the Exchangeable Sodium Percentage, but precautions
      are needed to avoid the build up of toxic concentrations of trace metals in the
      soil, especially vanadium.

PMID- 28501336
TI  - Bioethanol production from recovered napier grass with heavy metals.
AB  - Using plants to absorb and accumulate heavy metals from polluted soil, followed
      by the recycling of explants containing heavy metals, can help achieve the goal
      of reverting contaminated soil to low heavy-metal content soil. However, the re
      use of recovered explants can also be problematic. Meanwhile, bioethanol has
      become a popular energy source. In this study, napier grass was used for the
      remediation of soil contaminated with heavy metals (artificially contaminated
      soil). The influence of bioethanol production from napier grass after
      phytoremediation was also investigated. The concentration of Zn, Cd, and Cr in
      the contaminated soil was 1000, 100, and 250 mg/kg, respectively. After napier
      grass phytoremediation, the concentration (dry biomass) of Zn, Cd, and Cr in the
      explants was 2701.97 +/- 173.49, 6.1 +/- 2.3, and 74.24 +/- 1.42 mg/kg,
      respectively. Biomass production in the unpolluted soil was 861.13 +/- 4.23 g.
      The biomass production ratio in high Zn-polluted soil was only 3.89%, while it
      was 4.68% for Cd and 21.4% for Cr. The biomass obtained after napier grass
      phytoremediation was pretreated using the steam explosion conditions of 180 
      degrees C, for 10 min, with 1.5% H2SO2, followed by enzymatic hydrolysis. The
      efficiency of enzymatic hydrolysis for Zn-polluted biomass was 90% of the
      unpolluted biomass, while it was 77% for Cd, and approximately the same for Cr.
      The fermentation efficiency of the heavy-metal-containing biomass was higher than
      the control biomass. The fermentation ethanol concentration obtained was 8.69
      12.68, 13.03-15.50, and 18.48-19.31 g/L in Zn, Cd, and Cr environments,
      respectively. Results show that the heavy metals had a positive effect on
      bacteria fermentation. However, the fermentation efficiency was lower for biomass
      with severe heavy metal pollution. Thus, the utilization of napier grass
      phytoremediation for bioethanol production has a positive effect on the
      sustainability of environmental resources.

PMID- 28501337
TI  - Late In-Hospital Management of Patients Hospitalized with Acute Heart Failure.
AB  - Acute Heart Failure (AHF) hospitalization presents a significant financial burden
      and portends a poor prognosis following discharge. As such, there has been
      significant emphasis on the late inpatient management of patients hospitalized
      with AHF to ensure successful transition to the outpatient setting and to reduce
      overall readmission and mortality rates. Thorough discharge planning and a
      multidisciplinary team approach are essential and as outlined in this review
      should focus on four key elements: the assessment of patients' readiness for
      discharge, optimization of goal directed medical therapy and appropriate device
      therapy, patient education and transition to the outpatient care.

PMID- 28501338
TI  - Risk factors for metabolic syndrome after liver transplantation: A systematic
      review and meta-analysis.
AB  - INTRODUCTION: Metabolic syndrome is associated with increased risk of
      cardiovascular events, which contributes to the elevated mortality rate among
      liver transplant recipients. The objective of this systematic review and meta
      analysis was to assess the prevalence and risk factors for metabolic syndrome
      after liver transplantation. METHODS: The databases Medline and Scopus were
      searched for observational studies evaluating prevalence and risk factors for
      metabolic syndrome after liver transplantation. Meta-analyses were performed
      based on odds ratios (ORs) from multivariable analyses. The Newcastle-Ottawa
      Scale was used for assessment of bias. RESULTS: The literature search generated
      1815 records of which 16 articles were included comprising 3539 patients. The
      post-transplant prevalence of metabolic syndrome was 39%. Eight studies were
      eligible for meta-analyses, which showed that pre-transplant diabetes (OR=3.54,
      95% confidence interval (CI): 2.51-4.98) and pre-transplant obesity (OR=2.44, 95%
      CI: 1.48-4.03) were risk factors for metabolic syndrome. Six out of seven studies
      reported that recipients with metabolic syndrome had a higher incidence of
      cardiovascular events. Four studies showed that survival was not affected by
      metabolic syndrome. CONCLUSIONS: The prevalences of metabolic syndrome and new
      onset metabolic syndrome were high after liver transplantation. Metabolic
      syndrome was associated with cardiovascular events, but not poorer survival.
      Patients with pre-transplant diabetes and -obesity are at high risk of metabolic
      syndrome and should be under careful surveillance in order to prevent, earlier
      diagnose, and treat metabolic syndrome and thereby limit the risk of
      cardiovascular events.

PMID- 28501339
TI  - X-ray free electron laser single-particle analysis for biological systems.
AB  - The X-ray free electron laser (XFEL) is a new light source that can produce
      coherent, ultra-brilliant, femtosecond X-ray pulses. This X-ray beam provides new
      possibilities for studies in structural biology. In this review, we survey the
      applications of XFEL to biological systems, with an emphasis on studies of
      noncrystalline samples. Although atomic-level modeling is not yet achievable,
      this method enables high-throughput, damage-free imaging of biological samples
      under near-physiological conditions and is being rapidly developed. Here, we
      provide overviews of XFEL technology, experimental techniques, and computational
      data analyses, and discuss examples of such studies.

PMID- 28501340
TI  - Gliding Resistance After Epitendinous-First Repair of Flexor Digitorum Profundus
      in Zone II.
AB  - PURPOSE: The importance of flexor tendon repair with both core and epitendinous
      suture placement has been well established. The objective of this study was to
      determine whether suture placement order affects gliding resistance and bunching
      in flexor digitorum profundus tendons in a human ex vivo model. METHODS: The
      flexor digitorum profundus tendons of the index, middle, ring, and little fingers
      of paired cadaver forearms were tested intact for excursion and mean gliding
      resistance in flexion and extension across the A2 pulley. Tendons were
      subsequently transected and repaired with either an epitendinous-first (n = 12)
      or a control (n = 12) repair. Gliding resistance of pair-matched tendons were
      analyzed at cycle 1 and during the steady state of tendon motion. The tendon
      repair breaking strength was also measured. RESULTS: The mean steady state
      gliding resistance was less for the epitendinous-first repair than for the
      control repair in flexion (0.61 N vs 0.72 N) and significantly less in extension
      (0.68 N vs 0.85 N). Similar results were seen for cycle 1. None of the repairs
      demonstrated gap formation; however, control repairs exhibited increased
      bunching. Load to failure was similar for both groups. CONCLUSIONS: The order of
      suture placement for flexor tendon repair is important. Epitendinous-first repair
      significantly decreased mean gliding resistance, allowed for easier placement of
      core sutures, and resulted in decreased bunching. CLINICAL RELEVANCE:
      Epitendinous-first flexor tendon repairs may contribute to improved clinical
      outcomes compared with control repairs by decreasing gliding resistance and
      bunching.

PMID- 28501341
TI  - Chronic Boutonniere Deformity: Cross-Lateral Band Technique Using Palmaris Longus
      Autograft.
AB  - PURPOSE: The purpose of this study was to evaluate the outcomes of treatment of
      chronic boutonniere deformity with a reconstruction technique using palmaris
      longus autograft. MATERIALS AND METHODS: Seven patients with chronic,
      posttraumatic, flexible boutonniere deformities referred to our clinic between
      January 2010 and September 2014 were included in the study. In all 7 patients,
      the lateral bands were deficient or damaged beyond repair. A novel reconstruction
      technique for chronic boutonniere deformity utilizing palmaris longus autograft
      was used. The 2 lateral bands were reconstructed by attaching the palmaris longus
      tendon grafts from the lateral part of the central slip proximally to the volar
      aspect of the distal phalanx distally using pull-out sutures. The grafts were
      positioned so that they crossed over one another at the level of the middle
      phalanx. The patients were followed for a mean of 14 months (range, 12-16
      months). The principal outcome measure was the range of motion of the proximal
      (PIP) and distal (DIP) interphalangeal joints. RESULTS: Before surgery, the
      average PIP joint active flexion was 69 degrees  (range, 60 degrees -85 degrees
      ). After surgery, the average PIP joint active flexion increased to 92 degrees 
      (range, 90 degrees -100 degrees ). Before surgery, the average PIP joint
      extension deficit was 54 degrees  (range, 40 degrees -60 degrees ); after
      surgery, the average deficit was reduced to 7 degrees  (range, 5 degrees -15
      degrees ). Before surgery, the average DIP posture was 9 degrees  of
      hyperextension (range, 5 degrees -12 degrees ); after surgery, DIP hyperextension
      was reduced to 2 degrees  (range, 0 degrees -5 degrees ). Before surgery, the
      average DIP active flexion was 40 degrees  (range, 35 degrees -55 degrees );
      after surgery, this increased to 55 degrees  (range, 43 degrees -72 degrees ). No
      patients developed a DIP flexion contracture. CONCLUSIONS: In the chronic
      boutonniere deformity, when the lateral bands are deficient or damaged, our cross
      lateral band reconstruction technique using palmaris longus autograft is a
      treatment option with satisfactory results. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic V.

PMID- 28501342
TI  - Speed, age, sex, and body mass index provide a rigorous basis for comparing the
      kinematic and kinetic profiles of the lower extremity during walking.
AB  - The increased use of gait analysis has raised the need for a better understanding
      of how walking speed and demographic variations influence asymptomatic gait.
      Previous analyses mainly reported relationships between subsets of gait features
      and demographic measures, rendering it difficult to assess whether gait features
      are affected by walking speed or other demographic measures. The purpose of this
      study was to conduct a comprehensive analysis of the kinematic and kinetic
      profiles during ambulation that tests for the effect of walking speed in parallel
      to the effects of age, sex, and body mass index. This was accomplished by
      recruiting a population of 121 asymptomatic subjects and analyzing characteristic
      3-dimensional kinematic and kinetic features at the ankle, knee, hip, and pelvis
      during walking trials at slow, normal, and fast speeds. Mixed effects linear
      regression models were used to identify how each of 78 discrete gait features is
      affected by variations in walking speed, age, sex, and body mass index. As
      expected, nearly every feature was associated with variations in walking speed.
      Several features were also affected by variations in demographic measures,
      including age affecting sagittal-plane knee kinematics, body mass index affecting
      sagittal-plane pelvis and hip kinematics, body mass index affecting frontal-plane
      knee kinematics and kinetics, and sex affecting frontal-plane kinematics at the
      pelvis, hip, and knee. These results could aid in the design of future studies,
      as well as clarify how walking speed, age, sex, and body mass index may act as
      potential confounders in studies with small populations or in populations with
      insufficient demographic variations for thorough statistical analyses.

PMID- 28501343
TI  - Changes of renal sinus fat and renal parenchymal fat during an 18-month
      randomized weight loss trial.
AB  - BACKGROUND & AIMS: Data regarding the role of kidney adiposity, its clinical
      implications, and its dynamics during weight-loss are sparse. We investigated the
      effect of long-term weight-loss induced intervention diets on dynamics of renal
      sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation
      within the renal parenchyma. METHODS: We randomized 278 participants with
      abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate
      diets, with or without exercise. We quantified renal-sinus-fat and %renal
      parenchymal-fat by whole body magnetic-resonance-imaging. RESULTS: Participants
      (age = 48 years; 89% men; body-mass-index = 31 kg/m2) had 86% retention to the
      trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat
      were directly associated with hypertension, and with higher abdominal deep
      subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for
      all) after adjustment for body weight. Higher renal-sinus-fat was associated with
      lower estimated-glomerular-filtration-rate and with higher microalbuminuria and
      %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus
      fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13
      vs. baseline) significantly decreased, and similarly across the intervention
      groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with
      weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral
      adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with
      decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with
      decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (beta = 0.13;
      p = 0.05), triglycerides/HDL-c (beta = 0.13; p = 0.05), insulin (beta = 0.12; p =
      0.05) and gamma glutamyl transpeptidase (beta = 0.24; p = 0.001), but not with
      improved renal function parameters or blood pressure. Decreased intake of sodium
      was associated with a reduction in %renal-parenchymal-fat, after adjustment for
      18 months weight-loss (beta = 0.15; p = 0.026) and hypertension (beta = 0.14; p =
      0.04). CONCLUSIONS: Renal-sinus-fat and renal-parenchymal-fat are fairly related
      to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic
      parameters, independent of changes in weight or hepatic fat, rather than with
      improved renal function or blood pressure parameters. CLINICALTRIALS.
      GOVIDENTIFIER: NCT01530724.

PMID- 28501344
TI  - Kaposi Sarcoma and Lung Transplant: Two Case Reports.

PMID- 28501345
TI  - Incidental Finding of Right Pulmonary Artery Agenesis in an Adult.

PMID- 28501346
TI  - IL-13 and idiopathic pulmonary fibrosis: Possible links and new therapeutic
      strategies.
AB  - The recent advances in the knowledge of immunological aspects of many pulmonary
      diseases, allowed to identify cells, biological functions, cytokines, and
      receptors that are preferentially involved in each disease. This is the case of
      asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The
      role of IL-13 is strictly related, via complex signaling pathways, to eosinophil
      recruitment and activation, to mucus secretion, periostin generation and to
      fibrogenic processes (which are part of the remodeling process). These peculiar
      roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary
      Fibrosis, and consequently of its antagonists in the treatment of such disease.
      We review herein the immunological roles of IL-13 in asthma and IPF, and the
      currently ongoing attempts to treat IPF by IL-13 antagonism strategies.

PMID- 28501347
TI  - Defective protein prenylation is a diagnostic biomarker of mevalonate kinase
      deficiency.

PMID- 28501349
TI  - Potential health impact and cost-effectiveness of drug therapy for
      prehypertension.
AB  - BACKGROUND: Studies have reported that pharmacologic interventions with
      candesartan or ramipril could reduce the risk of hypertension among
      prehypertensive subjects free of clinical cardiovascular disease (CVD), however,
      the cost-effectiveness and long-term cardiovascular risk of drug treatment among
      these population is unclear. METHOD: A Markov state-transition model was
      developed to simulate a hypothetical cohort of Chinese adults with high-range
      prehypertension (130-139/85-89mmHg) but without CVD. Data on the incidence of CVD
      and hypertension was obtained from corresponding risk equations. Utility and
      disease-related costs were obtained from published literatures. Robustness and
      uncertainty was evaluated using deterministic and probabilistic sensitivity
      analyses. RESULTS: Compared with placebo, drug treatment resulted in delaying the
      development of hypertension by nearly 12years and reducing the absolute incidence
      of hypertension by 32.01% over lifetime. The cumulative incidence of coronary
      heart disease, stroke and heart failure were reduced and survival was improved
      from 28.46 to 28.80years. The average incremental cost effectiveness ratio for
      drug treatment was $12,994 per quality-adjusted life-year and the value was
      mostly sensitive to the effect size of treatment and age starting treatment. At a
      willingness-to-pay threshold of >3*China gross domestic product per capita in
      2014, there was a 30.48% chance that drug treatment would remain cost-effective
      and a low chance of being cost-effective if relative risk of treatment on
      hypertension was larger than 0.64. CONCLUSION: Drug treatment for prehypertension
      may help stem the current epidemic of hypertension among Chinese adults free of
      CVD, which may in turn reduce CVD complications and potentially be cost
      effective.

PMID- 28501348
TI  - Single-Cell RNA Sequencing: Unraveling the Brain One Cell at a Time.
AB  - Single-cell RNA sequencing (scRNA-seq) is an exciting new technology allowing the
      analysis of transcriptomes from individual cells, and is ideally suited to
      address the inherent complexity and dynamics of the central nervous system. scRNA
      seq has already been applied to the study of molecular taxonomy of the brain.
      These works have paved the way to expanding our understanding of the nervous
      system and provide insights into cellular susceptibilities and molecular
      mechanisms in neurological and neurodegenerative diseases. We discuss recent
      progress and challenges in applying this technology to advance our understanding
      of the brain. We advocate the application of scRNA-seq in the discovery of
      targets and biomarkers as a new approach in developing novel therapeutics for the
      treatment of neurodegenerative diseases.

PMID- 28501350
TI  - First in man prolonged pressure-controlled intermittent coronary sinus occlusion
      to treat refractory left ventricular dysfunction and ischemia with patent
      epicardial coronary arteries.
AB  - AIMS: Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO)
      intermittently increases the pressure in the cardiac venous outflow tract using a
      balloon-tipped catheter introduced percutaneously into the coronary sinus. It
      aims to improve microvascular perfusion in STEMI patients during PCI, thus
      improving infarct healing. Its successful administration was associated with an
      improvement in myocardial recovery four months after primary-PCI as compared to
      control. However, it has never been used in other settings or for a prolonged
      period. The aim of this study was to report on the feasibility and efficacy of
      prolonged PICSO to treat refractory LV dysfunction and ischemia. METHODS AND
      RESULTS: Two patients with refractory LV dysfunction and ongoing ischemia with
      patent epicardial coronary artery and suspected underlying microvascular
      dysfunction were treated with prolonged off-label PICSO utilization. A medium of
      23,990mmHg PICSO quantity (a marker of PICSO therapy performance) was achieved:
      it was almost fifty times the PICSO quantity previously reported in in short-term
      PICSO utilization. After PICSO placement, both patients showed significant
      improvement of myocardial ischemia and recovery of LV systolic function.
      CONCLUSION: Prolonged PICSO utilization was feasible and effective in two
      patients. These cases highlight a novel application of PICSO technology:
      redistribution of venous blood and improvement in microvascular perfusion that
      might be a new target in cases of refractory LV dysfunction and ongoing ischemia
      in the setting of patent epicardial coronary arteries.

PMID- 28501351
TI  - Author's reply: Assessment of current use of guideline-based medical therapy in
      elderly patients with heart failure.

PMID- 28501352
TI  - Effects of glucagon-like peptide-1 receptor agonists on mortality and
      cardiovascular events: A comprehensive meta-analysis of randomized controlled
      trials.
AB  - INTRODUCTION: The publication of the results of LEADER and SUSTAIN-6 trials
      suggested a possible beneficial effect of the class of GLP-1 receptor agonists on
      cardiovascular morbidity and mortality. The aim of the present meta-analysis is
      to collect and synthetize all available evidence on the effect of GLP-1 receptor
      agonists on cardiovascular events and mortality. METHODS: A Medline search for
      GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide,
      dulaglutide, or semaglutide) was performed, collecting all randomized clinical
      trials with a duration >11weeks, enrolling patients with type 2 diabetes, and
      comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor
      agonist drug. The principal outcome of this analysis was the effect of GLP-1
      receptor agonists on all-cause and cardiovascular mortality, overall (fatal plus
      nonfatal) myocardial infarction, stroke, and heart failure. RESULTS: Out of 113
      trials fulfilling inclusion criteria (mean duration 41.7+/-38.2weeks), 32, 25,
      48, 43 and 32 reported at least one event for all-cause and cardiovascular
      mortality, overall (fatal plus nonfatal) myocardial infarction, stroke, and heart
      failure, respectively. In GLP-1 receptor agonist-treated patients, all-cause
      mortality, cardiovascular mortality, and myocardial infarction were significantly
      lower than in comparators (MH-OR [95% CI] 0.88 [0.79-0.97], p=0.015, 0.84 [0.74
      0.96], p=0.009, and 0.90 [0.80-1.00], p=0.050, respectively), whereas no
      beneficial effect was observed for stroke and heart failure (MH-OR [95% CI] 0.90
      [0.81-1.00]. p=0.059. 0.89 [0.76-1.04]. p=0.15. and 0.92 [0.81-1.06]. p=0.25.
      respectively). CONCLUSIONS: Overall, the agents of this class appear to reduce
      all-cause mortality, cardiovascular mortality, and the incidence of myocardial
      infarction at mid-term follow up.

PMID- 28501353
TI  - Beta-tricalcium phosphate for orthopedic reconstructions as an alternative to
      autogenous bone graft.
AB  - : Autogenous bone graft (autograft) remains the gold standard in the treatment of
      many orthopedic problems. However, graft harvest can lead to perioperative
      morbidity and increased cost. We tested the hypothesis that an osteoconductive
      matrix, beta-tricalcium phosphate (beta-TCP), would be a safe and effective
      alternative to autograft alone. Beta-tricalcium phosphate (beta-TCP) is
      considered as one of the most promising biomaterials for bone reconstruction.
      This study analyzes the outcomes of patients who received beta-TCP as bone
      substitutes in orthopedic surgery. METHODS: A total of 50 patients were enrolled
      in a controlled, non-inferiority clinical trial to compare the safety and
      efficacy of beta-TCP (25 patients) with those of autograft (25 patients) in
      indications requiring usually autograft. These 50 patients were categorized
      according to the etiology and morphology of the 54 bone defects resulting from
      elective surgical procedures, such as 34 open-wedge high tibial osteotomies, and
      20 osteonecrosis treatments with core decompression. Radiographic (healing
      process with or without integration of beta-TCP), clinical (no other surgical
      procedure), functional outcomes and safety (with or without complications) were
      assessed through fifty-two weeks postoperatively. RESULTS: With regard to the
      primary endpoint (radiographic evolution), the fusion rate of the 34 open-wedge
      osteotomies was 100% (17 among 17) for patients in the group with beta-TCP
      compared with 94% (16 among 17) for patients in the autograft group. For the 20
      cavitary defects (osteonecrosis), the radiographic union rates, as determined by
      the presence of osseous bridging, were 100% for patients in the group with beta
      TCP and 100% for those in the autograft group. Clinically at one year, all
      quality-of-life and functional outcome data supported non-inferiority of beta-TCP
      compared with autograft, and patients in the beta-TCP group were found to have
      less pain and an improved safety profile. CONCLUSIONS: Treatment with beta-TCP
      resulted in comparable fusion rates, less pain and fewer side effects as compared
      with treatment with autograft. This study established clinical parameters where
      the beta-TCP alone can successfully support the osteogenic process.

PMID- 28501354
TI  - Calcium orthophosphates (CaPO4): Occurrence and properties.
AB  - The present overview is intended to point the readers' attention to the important
      subject of calcium orthophosphates (CaPO4). This type of materials is of the
      special significance for the human beings because they represent the inorganic
      part of major normal (bones, teeth and antlers) and pathological (those appearing
      due to various diseases) calcified tissues of mammals. For example,
      atherosclerosis results in blood vessel blockage caused by a solid composite of
      cholesterol with CaPO4, while dental caries (tooth decay) and osteoporosis (a low
      bone mass with microarchitectural changes) mean a partial decalcification of
      teeth and bones, respectively, that results in replacement of a less soluble and
      harder biological apatite by more soluble and softer calcium
      hydrogenorthophosphates. Due to the compositional similarities to the calcified
      tissues of mammals, CaPO4 are widely used as biomaterials for bone grafting
      purposes. In addition, CaPO4 have many other applications. Thus, there is a great
      significance of CaPO4 for the humankind and, in this paper, an overview on the
      current knowledge on this subject is provided.

PMID- 28501355
TI  - Sono-photo-Fenton oxidation of bisphenol-A over a LaFeO3 perovskite catalyst.
AB  - In this study, oxidation of bisphenol-A (IUPAC name - 2,2-(4,4-dihydroxyphenyl,
      BPA), which is an endocrine disrupting phenolic compound used in the
      polycarbonate plastic and epoxy resin industry, was investigated using sono-photo
      Fenton process under visible light irradiation in the presence of an iron
      containing perovskite catalyst, LaFeO3. The catalyst prepared by sol-gel method,
      calcined at 500 degrees C showed a catalytic activity in BPA oxidation using sono
      photo-Fenton process with a degradation degree and a chemical oxygen demand (COD)
      reduction of 21.8% and 11.2%, respectively. Degradation of BPA was studied by
      using individual and combined advanced oxidation techniques including sonication,
      heterogeneous Fenton reaction and photo oxidation over this catalyst to
      understand the effect of each process on degradation of BPA. It was seen, the
      role of sonication was very important in hybrid sono-photo-Fenton process due to
      the pyrolysis and sonoluminescence effects caused by ultrasonic irradiation. The
      prepared LaFeO3 perovskite catalyst was a good sonocatalyst rather than a
      photocatalyst. Sonication was not only the effective process to degrade BPA but
      also it was the cost effective process in terms of energy consumption. The
      studies show that the energy consumption is lower in the sono-Fenton process than
      those in the photo-Fenton and sono-photo- Fenton processes.

PMID- 28501357
TI  - Medicaid Reform: Key Considerations for Children's Health Care.

PMID- 28501358
TI  - The Zero-LDL Hypothesis. Towards Extremely Low LDL Concentrations.

PMID- 28501356
TI  - Engaging Overweight Adolescents in a Health and Fitness Program Using Wearable
      Activity Trackers.
AB  - INTRODUCTION: Our objectives were to (a) examine feasibility and receptivity of
      overweight adolescents joining a community-based group fitness program and (b)
      test preliminary efficacy of a 12-week pilot intervention designed to promote
      health, fitness, and self-efficacy for the identified teens. METHODS: The 12-week
      fitness program for overweight adolescents was developed and included planned
      physical activities, nutrition classes, and goal-setting sessions. A one-group
      pre-/posttest study design evaluated 20 participants from grades 10 through 12
      who enrolled in the program pilot study. Participants were given a wearable
      activity tracker that captured data using an Internet-based platform. Outcome
      measures included body mass index, screen time, fitness, and cardiovascular
      measures. RESULTS: A community fitness program for overweight adolescents was
      successfully implemented. High school students were receptive to the intervention
      and reported high program satisfaction. Positive effects included measurements of
      strength, systolic blood pressure, weight, and screen time behaviors. DISCUSSION:
      This study provides evidence to support the feasibility, acceptance, and
      preliminary effects of the pilot program with overweight adolescents.

PMID- 28501359
TI  - The Ebola epidemic in Liberia and managing the dead-A future role for
      Humanitarian Forensic Action?
AB  - With some of their economies, communities and health systems weakened by decades
      of war and poor governance, it was no accident that an epidemic of Ebola virus
      disease broke out in west Africa. Being spread in part by contact with body
      fluids of those who had died from the disease, funerary rites and the way dead
      bodies were managed were important modes of transmission. The Liberian Red Cross,
      supported by the International Federation of Red Cross and Red Crescent Societies
      and the International Committee of the Red Cross, undertook the challenging task
      of managing the dead bodies in Monrovia during the epidemic. The work was
      undertaken by volunteers, not health care workers, who were trained and equipped
      for this task. The authors observed their work and were impressed. Valuable
      lessons were learned for mortuaries generally, and for Humanitarian Forensic
      Action involving the management of highly infectious human remains.

PMID- 28501360
TI  - Cow urine, Indian yellow, and art forgeries: An update.
AB  - In a recent technical note in this Journal, de Faria et al., 2017 [1] reported
      the Raman spectrum of authentic Indian yellow artists' pigment, correcting a
      decades old reference spectrum that has led to the misidentification of this
      pigment in artworks that actually contained tartrazine yellow. The present
      communication provides additional information and corrects important experimental
      details mentioned by de Faria et al. that should lead to further identifications
      of the authentic pigment in artworks. Despite their claim that the analysis of
      this naturally fluorescent colorant is only possible with Fourier transform (FT)
      instruments, the ready characterization of two authentic samples of historic
      Indian yellow pigment is demonstrated here using commonly available visible and
      near-infrared excitation sources on a dispersive Raman microspectrometer. To
      highlight the importance of the proper identification of dyes and colorants, the
      authentication and art historical implications of previous literature reports
      that have misidentified Indian yellow on historic documents are more thoroughly
      discussed here from a forensic science point of view. The numerous modern
      pigments that are sold as imitation Indian yellow are addressed and analyzed,
      allowing the ready noninvasive detection of anachronistic colorants in attempted
      forgeries. Finally, this unusual pigment is positively identified for the first
      time using non-invasive dispersive Raman microspectroscopy on a historic object
      of uncertain date, a highly decorative manuscript from the Indian subcontinent.

PMID- 28501361
TI  - Intrauterine insemination with gonadotropin stimulation or in vitro fertilization
      for the treatment of unexplained subfertility: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the best first line management option for the treatment of
      unexplained subfertility-controlled ovarian hyperstimulation (COH) with
      gonadotropins and IUI or IVF. DESIGN: Randomized controlled trial. SETTING:
      Single center trial in a tertiary referral unit. PATIENT(S): Couples with
      unexplained subfertility. INTERVENTION(S): Couples were randomized to receive
      either three cycles of IUI + COH or one cycle of IVF. MAIN OUTCOME MEASURE(S):
      Singleton pregnancy rate (PR) per couple. RESULT(S): A total of 207 couples were
      randomly assigned to three cycles of IUI + COH (n = 101) or one cycle of IVF (n =
      106). There were 25 (24.7%) singleton live births for the IUI + COH group and 33
      (31.1%) for the IVF group (relative risk, 1.3; 95% confidence interval [CI] 0.81
      1.96) with an absolute risk difference of 6.4% (95% CI -5.8% to 18.6%). The
      multiple pregnancies per live birth were 4 (13.8%) for the IUI + COH group and 3
      (8.3%) for the IVF group (relative risk, 0.6; 95% CI 0.14-2.4). There were no
      cases of ovarian hyperstimulation syndrome (OHSS) in the IUI group and three
      cases of OHSS (3.7%) in the IVF group. There were 17 live births from spontaneous
      conception in between treatment cycles (8.2%). CONCLUSION(S): The singleton live
      birth rate with one cycle of IVF was not significantly different than three
      cycles of IUI + COH. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN43430382.

PMID- 28501363
TI  - Sex and gender: you should know the difference.

PMID- 28501364
TI  - Immune modulation treatments-where is the evidence?
AB  - While advances in assisted reproductive techniques have been substantial, failure
      of the apparently viable embryo to implant remains a source of distress and
      frustration to patients and specialists alike. The unique maternal immunological
      response to the embryo and the notion that defects in early placentation underlie
      the great complications of pregnancy have focused attention on the therapeutic
      potential of peri-implantation immunomodulation. On the face of it, the rationale
      for this approach is very attractive. However, as will be argued in this review,
      the clinical evidence base supporting the use of immunosuppressive treatments is
      weak and difficult to apply in practice and fails the needs of both doctors and
      their patients. This evidence gap is filled by justifications that are based
      largely on meeting patient expectations and commercial imperatives. However, this
      does not mean that immunomodulation treatments should be written off as
      ineffective. The literature in this field, while suffering the same challenges of
      heterogeneity, small studies, and publication bias as other areas of medicine,
      does hint at the way forward. Recurrent implantation failure and pregnancy loss
      are not diagnoses but clinical presentations that require appropriate phenotyping
      and etiological investigation. We are increasingly gaining the tools to make an
      "endometrial diagnosis," and these will allow us to design clinical studies of
      interventions that treat the underlying cause rather than the symptoms of
      implantation failure. The current evidence base does not support the clinical use
      of immunomodulation therapies in patients undergoing IVF. However, more
      discerning phenotyping may identify groups who could benefit.

PMID- 28501362
TI  - Mode of conception does not appear to affect placental volume in the first
      trimester.
AB  - OBJECTIVE: To study whether infertility treatments, including IVF and non-IVF
      fertility treatments, are associated with diseases of placental insufficiency in
      early gestation. First trimester placental volumes by ultrasound and chorionic
      villi weight during sampling (CVS) were performed to detect differences between
      pregnancies conceived spontaneously versus with fertility treatments. DESIGN:
      Retrospective cohort. SETTING: Academic tertiary center. PATIENT(S): Women with
      singleton pregnancies undergoing CVS and first trimester ultrasound from April
      2007 to November 2015. INTERVENTION(S): Estimated placental volume (EPV) was
      calculated from ultrasound images using a validated computation and CVS estimated
      tissue weight was performed using a validated visual analogue scale. MAIN OUTCOME
      MEASURE(S): Adjusted linear regression was used to compare EPV and CVS weight
      based on mode of conception. RESULT(S): A total of 1,977 spontaneous and 334
      conceived with fertility treatments (133 non-IVF and 201 IVF) pregnancies were
      included. Significant differences in maternal age, gravidity, hypertension, and
      smoking status were identified. EPV and CVS weight were correlated with maternal
      age, gestational age, and maternal hypertension. Adjusted linear regression
      showed no difference in EPV in pregnancies conceived with fertility treatments
      versus spontaneously. The CVS weight was significantly lower in the IVF
      conceptions in unadjusted univariate analyses. However, after adjusted
      regression, this was no longer significant. CONCLUSION(S): Mode of conception
      does not appear to affect first trimester placental size. As differences in
      maternal age, hypertension, and smoking status differ among the groups and are
      correlated to placental size, it may be the underlying patient population leading
      to abnormal placentation and insufficiency, not the fertility treatments used.

PMID- 28501365
TI  - Why natural killer cells are not enough: a further understanding of killer
      immunoglobulin-like receptor and human leukocyte antigen.
AB  - The immune system's role in recurrent reproductive failure is a controversial
      issue in assisted reproduction. Most studies into immune system implication in
      reproduction have focused on finding markers of peripheral blood and less on the
      uterine environment. Peripheral blood natural killer cells have become an "immune
      study core" for women with recurrent miscarriage or recurrent implantation
      failure, based on the mistaken notion that they cause reproductive failure by
      killing or "rejecting" the embryo. Maternal-fetal tolerance begins at the uterine
      level, so successful adaptation to the fetus occurs after a complicated process.
      Insufficient uterine lining invasion by an invading extravillous trophoblast is
      the primary defect in pregnancy disorders such as recurrent miscarriage. This
      process is regulated by the interaction between maternal killer immunoglobulin
      like receptors (KIRs), expressed by uterine natural killer cells (uNK), and their
      ligand human leukocyte antigen (HLA) C, expressed by the extravillous
      trophoblast. Pregnancies are an increased risk of disorders in mothers with KIR
      AA when the fetus has paternal HLA-C2. A recent report has indicated that the
      expression of more than one paternal HLA-C by the extravillous trophoblast in
      assisted reproduction may affect placentation in mothers with KIR AA. This review
      provides insight into the immune system's role in assisted reproductive
      treatments. These insights can have an impact on the selection of single-embryo
      transfer and/or oocyte/sperm donor according to HLA-C in patients with recurrent
      implantation failure and recurrent miscarriage depending on their KIR haplotype.

PMID- 28501366
TI  - Reproductive outcomes after a single dose of gonadotropin-releasing hormone
      agonist compared with human chorionic gonadotropin for the induction of final
      oocyte maturation in hyper-responder women aged 35-40 years.
AB  - OBJECTIVE: To investigate the reproductive outcomes after the use of GnRH agonist
      (GnRHa) compared with hCG for the induction of final oocyte maturation in GnRH
      antagonist cycles performed in hyper-responder women aged 35-40 years. DESIGN:
      Retrospective study. SETTING: Academic fertility center. PATIENT(S): Two hundred
      seventy-two hyper-responder women aged 35-40 years who underwent controlled
      ovarian stimulation under GnRH antagonist suppression were included. Final oocyte
      maturation was performed with GnRHa (n = 168) or hCG (n = 104). Embryos were
      cryopreserved at the blastocyst stage and transferred in subsequent warming
      cycles (n = 542). Subjects were included in the analysis until live birth was
      achieved, after which they were excluded from further analysis. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Cumulative live birth rate. RESULT(S): Subjects in
      the GnRHa group achieved a higher number of oocytes (22 vs. 21) and a higher
      number of mature oocytes (16 vs. 14). The number of cryopreserved blastocysts
      (median of five blastocysts in both groups) was similar. Women in the hCG group
      needed a lower number of warming cycles to achieve live birth (1.32 vs. 2.12),
      had higher embryo implantation rates (48% vs. 39%), and the proportion of embryos
      transferred until live birth was lower (33% vs. 57%). The cumulative live birth
      rate was similar between the groups (48.15% vs. 48%). CONCLUSION(S): Although the
      cumulative live birth rate is similar, a single dose of GnRHa possibly results in
      suboptimal oocyte and embryo competence, as manifested by decreased embryo
      implantation rates and increased time needed to achieve live birth.

PMID- 28501367
TI  - Old habits die hard: retrospective analysis of outcomes with use of
      corticosteroids and antibiotics before embryo transfer.
AB  - OBJECTIVE: To evaluate clinical pregnancy rates in embryo transfer (ET) cycles
      with and without peri-implantation corticosteroid and oral antibiotic
      administration. DESIGN: Retrospective cohort study. SETTING: University
      affiliated in vitro fertilization (IVF) clinic. PATIENT(S): Eight hundred and
      seventy-six ETs with or without the routine use of methylprednisolone and
      doxycycline. INTERVENTION(S): Embryo transfer procedures. MAIN OUTCOME
      MEASURE(S): Clinical pregnancy rates (CPR). RESULT(S): The CPR with the routine
      use of methylprednisolone and doxycycline was 56.1% compared with 61.5% after
      discontinuation of these medications. Ongoing pregnancy rates were 49.5% with
      medications versus 53.2% without medications. Of the cleavage-stage embryos, 79%
      underwent assisted hatching; among these, the CPR was 28.7% when treated with
      corticosteroids and antibiotics compared with 47.4% without medications.
      CONCLUSION(S): No statistically significant difference in overall IVF outcomes
      was noted after the discontinuation of routine peri-implantation corticosteroids
      and antibiotics. The use of these medications varies across the country and may
      be a result of habit rather than evidence-based medicine.

PMID- 28501368
TI  - Contribution of immunology to implantation failure of euploid embryos.
AB  - Outcomes in assisted reproduction have seen marked improvement. With increased
      ability in the embryology laboratory to use extended embryo culture which in turn
      enables other selective techniques, such as trophectoderm biopsy and
      comprehensive chromosome screening, the chance of success per embryo transfer is
      increased. However, even the selection of a euploid blastocyst, which selects out
      many embryonic factors, does not yield successful implantation and ultimately
      delivery in all cases. Among the factors that affect implantation failure of
      apparently reproductively competent embryos, the immune system has been perhaps
      both the most plausible and the most debated. There are data on T-helper cells,
      in particular the TH1-TH2 balance, peripheral and uterine natural killer cells,
      and autoantibodies, all of which have been shown to have variable effects on
      implantation. Many investigators have developed and used a wide range of immune
      tests and treatments aimed at manipulating the milieu to favor implantation.
      Although it is certain that the immune system plays a role in implantation, our
      understanding of the physiology, let alone the pathophysiology, remains
      incomplete. It is imperative that we gain more clear evidence of causes and test
      and implement treatment paradigms. In the meantime, immune testing or empirical
      treatment with the use of immune modulators must be approached with caution.

PMID- 28501369
TI  - Validation study of the SCREENIVF: an instrument to screen women or men on risk
      for emotional maladjustment before the start of a fertility treatment.
AB  - OBJECTIVE: To examine construct and criterion validity of the Dutch SCREENIVF
      among women and men undergoing a fertility treatment. DESIGN: A prospective
      longitudinal study nested in a randomized controlled trial. SETTING: University
      hospital. PATIENT(S): Couples, 468 women and 383 men, undergoing an
      IVF/intracytoplasmic sperm injection (ICSI) treatment in a fertility clinic,
      completed the SCREENIVF. MAIN OUTCOME MEASURE(S): Construct and criteria validity
      of the SCREENIVF. RESULT(S): The comparative fit index and root mean square error
      of approximation for women and men show a good fit of the factor model. Across
      time, the sensitivity for Hospital Anxiety and Depression Scale subscale in women
      ranged from 61%-98%, specificity 53%-65%, predictive value of a positive test
      (PVP) 13%-56%, predictive value of a negative test (PVN) 70%-99%. The sensitivity
      scores for men ranged from 38%-100%, specificity 71%-75%, PVP 9%-27%, PVN 92%
      100%. A prediction model revealed that for women 68.7% of the variance in the
      Hospital Anxiety and Depression Scale on time 1 and 42.5% at time 2 and 38.9% at
      time 3 was explained by the predictors, the sum score scales of the SCREENIVF.
      For men, 58.1% of the variance in the Hospital Anxiety and Depression Scale on
      time 1 and 46.5% at time 2 and 37.3% at time 3 was explained by the predictors,
      the sum score scales of the SCREENIVF. CONCLUSION(S): The SCREENIVF has good
      construct validity but the concurrent validity is better than the predictive
      validity. SCREENIVF will be most effectively used in fertility clinics at the
      start of treatment and should not be used as a predictive tool.

PMID- 28501370
TI  - Gamete donation: current practices, public opinion, and unanswered questions.

PMID- 28501371
TI  - Endometriosis on the uterosacral ligament: a marker of ureteral involvement.
AB  - OBJECTIVE: To evaluate the association between ultrasound measurements of
      endometriosis nodules on the uterosacral ligament (USL) and the risk of ureteral
      involvement, as well as to assess whether associations with other ultrasound
      variables increase the sensitivity and specificity of the diagnosis of ureteral
      endometriosis. DESIGN: Cross-sectional, observational study. SETTING: University
      hospital. PATIENT(S): Four hundred sixty-three women with deep infiltrating
      endometriosis (DIE). INTERVENTION(S): Patients diagnosed with DIE underwent
      transvaginal ultrasound endometriosis mapping before laparoscopic surgery for
      full excision of endometriotic lesions. MAIN OUTCOME MEASURE(S): Preoperative
      ultrasound evaluation, intra- and postoperative assessment, and anatomopathologic
      confirmation. RESULT(S): Of the 463 patients who participated in the study, 111
      (23.97%) presented with endometriosis nodules with USL involvement on ultrasound
      examination conducted by a single radiologist. Receiver operating characteristic
      curve analysis showed that the size of the USL nodule had a statistically
      significant association with ipsilateral ureteral involvement. After multivariate
      logistic regression, the variables reduction in ovarian mobility, ureteral
      changes on the right side, size of the USL nodule, and presence of endometrioma
      on the left side were significantly associated with a ureteral endometriosis
      nodule. However, the combined result for the variables cited was worse than the
      diagnostic analysis using only the size of the USL nodule. CONCLUSION(S):
      Uterosacral ligament nodules with ultrasound measurements of 1.75 cm and 1.95 cm
      on the right and left sides, respectively, significantly increase the risk of
      ureteral involvement. Even with the association of other ultrasound variables,
      there was no improvement in sensitivity. Therefore, USL nodule size is a key
      measure for therapeutic planning and consent of the patient.

PMID- 28501372
TI  - Exploring global recognition of quality midwifery education: Vision or fiction?
AB  - BACKGROUND: Midwifery education is the foundation for preparing competent
      midwives to provide a high standard of safe, evidence-based care for women and
      their newborns. Global competencies and standards for midwifery education have
      been defined as benchmarks for establishing quality midwifery education and
      practice worldwide. However, wide variations in type and nature of midwifery
      education programs exist. AIM: To explore and discuss the opportunities and
      challenges of a global quality assurance process as a strategy to promote quality
      midwifery education. DISCUSSION: Accreditation and recognition as two examples of
      quality assurance processes in education are discussed. A global recognition
      process, with its opportunities and challenges, is explored from the perspective
      of four illustrative case studies from Ireland, Kosovo, Latin America and
      Bangladesh. The discussion highlights that the establishment of a global
      recognition process may assist in promoting quality of midwifery education
      programs world-wide, but cannot take the place of formal national accreditation.
      In addition, a recognition process will not be feasible for many institutions
      without additional resources, such as financial support or competent evaluators.
      In order to achieve quality midwifery education through a global recognition
      process the authors present 5 Essential Challenges for Quality Midwifery
      Education. CONCLUSION: Quality midwifery education is vital for establishing a
      competent workforce, and improving maternal and newborn health. Defining a global
      recognition process could be instrumental in moving toward this goal, but dealing
      with the identified challenges will be essential.

PMID- 28501373
TI  - Evaluating Appropriate Use of Pediatric Echocardiograms for Chest Pain in
      Outpatient Clinics.
AB  - BACKGROUND: Echocardiography is often used in the evaluation of pediatric chest
      pain, but the incidence of cardiac pathology is low. In 2014, the American
      College of Cardiology published appropriate use criteria (AUC) for
      echocardiography including recommendations for pediatric chest pain. We evaluated
      the frequency and diagnostic yield of echocardiograms performed for each AUC
      indication and cost associated with echocardiograms performed for indications
      meeting the "rarely appropriate" criteria. METHODS: Retrospective, single
      institution study of all patients 18 years or younger undergoing an initial
      evaluation for chest pain by a pediatric cardiologist (2014-15). We categorized
      the appropriateness of indications for echocardiograms on the basis of the AUC.
      We used multivariable logistic regression to determine factors associated with
      performance of an echocardiogram with the "rarely appropriate" indication. Excess
      costs associated with nondiagnostic echocardiograms meeting the "rarely
      appropriate" criteria were estimated using the Healthcare Bluebook to estimate a
      fair market price. RESULTS: The cohort included 539 patients, median age 13 years
      (range, 3-18) and 51.0% female. With retrospective application of the AUC,
      echocardiogram indications were classified as "appropriate" (304/539, 56.4%),
      "maybe appropriate" (68/539, 12.6%), and "rarely appropriate" (167/539, 31.0%).
      Echocardiograms were performed in 70.5% (380/539) of patients overall and in
      35.9% (60/167) of patients with "rarely appropriate" indications. Of those
      undergoing echocardiography, abnormal findings were present in 5.0% (19/380) and
      incidental findings in 2.6% (10/380); however, only one echocardiogram (0.3%) led
      to a diagnosis considered to be contributory to the patient's chest pain. There
      were no abnormal findings in the "rarely appropriate" subgroup. Provider use of
      echocardiography for "rarely appropriate" indications varied widely from 0 to 75%
      across 15 providers (P = .004). In multivariable analysis, provider clinical
      experience of >=20 years was associated with a lower rate of echocardiograms for
      "rarely appropriate" indications (odds ratio, 0.21 [95% CI, 0.09-0.47] vs.
      providers with <10 years' experience, P < .001). There was no significant
      association between race, ethnicity, age, sex, payer status, or total number of
      patients seen and performance of an echocardiogram meeting the "rarely
      appropriate" indications. Echocardiograms with "rarely appropriate" indications
      resulted in $47,578 in excess costs over the 1-year study. CONCLUSIONS:
      Echocardiogram use in patients meeting the "rarely appropriate" indication
      criteria is of little diagnostic utility and contributes to additional cost to
      the patient and health care system.

PMID- 28501375
TI  - Transthoracic Echocardiography versus Computed Tomography for Ascending Aortic
      Measurements in Patients with Bicuspid Aortic Valve.
AB  - BACKGROUND: Ascending aorta dilatation is common in bicuspid aortic valve (BAV).
      The aim of this study was to investigate agreement of transthoracic
      echocardiographic (TTE) measurement of the sinuses of Valsalva and the tubular
      mid-ascending aorta (Asc-Ao) compared with electrocardiographically gated
      computed tomographic angiographic (CTA) assessment in patients with BAV. METHODS:
      Fifty-three patients with BAV (mean age, 54 +/- 14 years; 74% men) who underwent
      both TTE and CTA imaging for ascending aortic assessment were retrospectively
      identified. All studies were measured de novo by experts. TTE measurements were
      obtained at the sinuses and the Asc-Ao, at both systole and end-diastole, using
      both leading edge-to-leading edge (L-L) and inner edge-to-inner edge (I-I)
      methods in the parasternal long-axis (LAX) view. The sinuses were also measured
      in the parasternal short-axis (SAX) view using the same methods plus mid
      diastole. CTA measurements were obtained in diastole using outer wall-to-outer
      wall (O-O) and inner wall-to-inner wall (I-I) methods. Correlation and agreement
      between the two imaging modalities were assessed using Lin correlation and Bland
      Altman analysis, respectively. RESULTS: Compared with CTA O-O maximum sinuses
      diameter, the best correlation and agreement were obtained using the TTE SAX mid
      diastolic L-L method (rho = 0.89, 2.6 +/- 2.3 mm, respectively). Compared with
      CTA O-O maximum Asc-Ao diameter, the TTE LAX systolic L-L method (rho = 0.93, 1.3
      +/- 2.5 mm) was best. Compared with CTA I-I maximum sinuses diameter, the TTE SAX
      mid-diastole L-L method (rho = 0.95, 0.6 +/- 2.2 mm) was unbiased. Compared with
      CTA I-I maximum Asc-Ao diameter, the TTE LAX end-diastolic L-L method (rho =
      0.95, 0.6 +/- 2.4 mm) was unbiased. CONCLUSIONS: In patients with BAV aortopathy,
      unbiased agreement between CTA and TTE imaging can be obtained between the CTA I
      I method and TTE SAX mid-diastolic L-L method for the sinuses and the TTE LAX end
      diastolic L-L method for the Asc-Ao. When using the CTA O-O method, the best
      agreement is obtained with the TTE SAX mid-diastolic L-L method for the sinuses
      (bias ~2 mm) and the TTE LAX systolic L-L method (bias ~1 mm) for the Asc-Ao.

PMID- 28501374
TI  - The Effect of the Superior Cavopulmonary Anastomosis on Ventricular Remodeling in
      Infants with Single Ventricle.
AB  - BACKGROUND: Infants with single ventricular physiology have volume and pressure
      overload that adversely affect ventricular mechanics. The impact of superior
      cavopulmonary anastomosis (SCPA) on single left ventricles versus single right
      ventricles is not known. METHODS: As part of the Pediatric Heart Network placebo
      controlled trial of enalapril in infants with single ventricular physiology,
      echocardiograms were obtained before SCPA and at 14 months and analyzed in a core
      laboratory. Retrospective analysis of the following measurements included single
      ventricular end-diastolic volume (EDV), end-systolic volume (ESV), mass, mass-to
      volume ratio (mass/volume), and ejection fraction. Qualitative assessment of
      atrioventricular valve regurgitation and assessment of diastolic function were
      also performed. RESULTS: A total of 156 participants underwent echocardiography
      at both time points. Before SCPA, mean ESV and mass Z scores were elevated (3.4
      +/- 3.7 and 4.2 +/- 2.9, respectively) as were mean EDV and mass/volume Z scores
      (2.1 +/- 2.5 and 2.0 +/- 2.9, respectively). EDV, ESV, and mass decreased after
      SCPA, but mass/volume and the degree of atrioventricular valve regurgitation did
      not change. Subjects with morphologic left ventricles demonstrated greater
      reductions in ventricular volumes and mass than those with right ventricles (mean
      change in Z score: left ventricular [LV] EDV, -1.9 +/- 2.1; right ventricular
      EDV, -0.7 +/- 2.5; LV ESV, -2.3 +/- 2.9; right ventricular ESV, -0.9 +/- 4.6; LV
      mass, -2.5 +/- 2.8; right ventricular mass, -1.3 +/- 2.6; P <= .03 for all).
      Approximately one third of patients whose diastolic function could be assessed
      had abnormalities at each time point. CONCLUSIONS: Decreases in ventricular size
      and mass occur in patients with single ventricle after SCPA, and the effect is
      greater in those with LV morphology. The remodeling process resulted in
      commensurate changes in ventricular mass and volume such that the mass/volume did
      not change significantly in response to the volume-unloading surgery.

PMID- 28501376
TI  - Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The
      Singapore Malay Eye Study.
AB  - PURPOSE: To determine the 6-year incidence of early and late age-related macular
      degeneration (AMD) in a Singaporean Malay population and to validate the Age
      Related Eye Disease Study (AREDS) simplified severity scale in Asians. DESIGN:
      Prospective, population cohort study. PARTICIPANTS: The Singapore Malay Eye Study
      baseline participants (age, >=40 years; 2006-2008) were followed up in 2011
      through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.
      METHODS: Fundus photographs were graded using the Wisconsin AMD grading system.
      MAIN OUTCOME MEASURES: Incidence of early and late AMD. RESULTS: Gradable fundus
      photographs were available for 1809 participants who attended both baseline and 6
      year follow-up examinations. The age-standardized incidences of early and late
      AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42
      1.29), respectively. The 5-year age-standardized incidence of early AMD
      (calculated based on the 6-year incidence) was lower in our population (5.58%;
      95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The
      incidence of late AMD in our population was similar to that of the Beaver Dam Eye
      Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye
      Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study
      population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD
      increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4,
      9.09%). CONCLUSIONS: This study documented the incidence of early and late AMD in
      a Malay population. The AREDS simplified severity scale is useful in predicting
      the risk of late AMD development in Asians.

PMID- 28501378
TI  - Incremental Revisions across the Life Span of Ophthalmic Devices after Initial
      Food and Drug Administration Premarket Approval, 1979-2015.
AB  - PURPOSE: To characterize the frequency, nature, and regulatory mechanisms by
      which ophthalmic devices are iteratively modified after initial Food and Drug
      Administration (FDA) Premarket Approval (PMA). DESIGN: Retrospective cross
      sectional analysis using publicly available FDA data. PARTICIPANTS: Ophthalmic
      devices initially approved via the FDA's PMA pathway between January 1, 1979 and
      December 31, 2015. METHODS: We used the FDA's PMA Database to identify and
      characterize initial approvals and subsequent postmarket modifications to Class
      III ophthalmic devices. The FDA Recalls Database was used to identify associated
      safety events. MAIN OUTCOME MEASURES: Median iterated life span (timespan across
      which modifications occurred after initial PMA) and median number of supplements
      approved per device, by device type, and overall, stratified by regulatory
      pathway and modification type. RESULTS: Between 1979 and 2015, the FDA approved
      168 original ophthalmic devices via the PMA pathway and 2813 subsequent
      modifications. More than one third (n = 64; 38%) of original approvals were
      intraocular lenses. Overall, devices underwent a median of 11 postmarket
      modifications (interquartile range [IQR], 3-24.8) across a median 10.0-year
      iterated life span (IQR, 4.1-16.7). The majority of devices (n = 144; 86%)
      underwent more than 1 postapproval modification, including more than 1 design
      modification (n = 84; 50%). The median number of changes altering device design
      or labeling was 3.5 (IQR, 1-9). Although manufacturing alterations (n = 834 of
      2813; 30%) were the most frequent type of revision, changes involving device
      design (n = 667; 24%) and labeling (n = 417; 15%) were common. Recalled devices
      underwent more frequent postapproval modifications per year (median, 1.4; IQR,
      0.7-2.3; mean, 1.5; 95% confidence interval, 1.1-1.9) in the period preceding
      recall than did nonrecalled devices (median, 0.5; IQR, 0.2-1.1; mean, 0.8; 95%
      confidence interval, 0.7-1.0) across their market approval period (P < 0.001).
      CONCLUSIONS: Most ophthalmic devices approved via the FDA's PMA pathway have
      undergone extensive revisions, including serial design and labeling changes,
      since their initial approvals, often without supporting clinical data.
      Ophthalmologists should take into consideration that cumulative revisions may
      render the clinical evidence that supported an original FDA approval less
      relevant to newer device models.

PMID- 28501377
TI  - Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular
      Degeneration.
AB  - PURPOSE: To examine the relationship between dark adaptation (DA) and optical
      coherence tomography (OCT)-based macular morphology in age-related macular
      degeneration (AMD). DESIGN: Prospective, cross-sectional study. PARTICIPANTS:
      Patients with AMD and a comparison group (>50 years) without any vitreoretinal
      disease. METHODS: All participants were imaged with spectral-domain OCT and color
      fundus photographs, and then staged for AMD (Age-related Eye Disease Study
      system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA
      extended protocol (20 minutes). A software program was developed to map the DA
      testing spot (2 degrees  circle, 5 degrees  superior to the fovea) to the OCT B
      scans. Two independent graders evaluated the B-scans within this testing spot, as
      well as the entire macula, recording the presence of several AMD-associated
      abnormalities. Multilevel mixed-effects models (accounting for correlated
      outcomes between 2 eyes) were used for analyses. MAIN OUTCOME MEASURES: The
      primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous
      variable. For subjects unable to reach RIT within the 20 minutes of testing, the
      value of 20 was assigned. RESULTS: We included 137 eyes (n = 77 subjects), 72.3%
      (n = 99 eyes) with AMD and the remainder belonging to the comparison group.
      Multivariable analysis revealed that even after adjusting for age and AMD stage,
      the presence of any abnormalities within the DA testing spot (beta = 4.8, P <
      0.001), as well as any abnormalities in the macula (beta = 2.4, P = 0.047), were
      significantly associated with delayed RITs and therefore impaired DA. In eyes
      with no structural changes within the DA testing spot (n = 76, 55.5%), the
      presence of any abnormalities in the remaining macula was still associated with
      delayed RITs (beta = 2.00, P = 0.046). Presence of subretinal drusenoid deposits
      and ellipsoid zone disruption were a consistent predictor of RIT, whether located
      within the DA testing spot (P = 0.001 for both) or anywhere in the macula (P <
      0.001 for both). Within the testing spot, the presence of classic drusen or
      serous pigment epithelium detachment was also significantly associated with
      impairments in DA (P <= 0.018). CONCLUSIONS: Our results suggest a significant
      association between macular morphology evaluated by OCT and time to dark-adapt.
      Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly
      associated with impaired dark adaptation.

PMID- 28501379
TI  - Metabolic impact of nutrient starvation in mevalonate-producing Escherichia coli.
AB  - The aim of this work was to enhance mevalonate yield from glucose in Escherichia
      coli by essential nutrient starvations and to reveal these effects on the central
      carbon metabolism. Stationary phase culture without essential nutrients such as
      nitrogen, sulfur, and magnesium was evaluated using an engineered E. coli
      introducing mvaE and mvaS genes from Enterococcus faecalis. Sulfur starvation
      resulted in the highest mevalonate yield of 0.61C-molC-mol-1 from glucose. The
      metabolic impacts of nutrient starvation were investigated by 13C-metabolic flux
      analysis. Under nitrogen starvation, the flux of the TCA cycle was large, causing
      high CO2 production. This was caused by degradation of mevalonate synthesis
      pathway enzymes. Under magnesium starvation, NADPH production was decreased,
      which limited mevalonate synthesis and promoted an overflow of acetate. Sulfur
      starvation not only suppressed the TCA cycle flux, but also supplied NADPH for
      mevalonate synthesis.

PMID- 28501380
TI  - CRISPRi mediated phosphoenolpyruvate carboxylase regulation to enhance the
      production of lipid in Chlamydomonas reinhardtii.
AB  - In this study, CRISPRi (clustered regularly interspaced short palindromic repeats
      interference) was used for the first time to regulate expression of exogenously
      supplied rfp gene as a proof-of-concept, and endogenous PEPC1 gene as a proof-of
      function in Chlamydomonas reinhardtii. The efficiency of 94% and stability of 7
      generations via CRISPRi mediated gene regulation in C. reinhardtii have been
      demonstrated by RFP. Gene PEPC1 encoding proteins are essential for controlling
      the carbon flux that enters the TCA cycle and plays a crucial role in carbon
      partitioning of substrates in competition with lipid synthesis. All CrPEPC1 down
      regulated strains have lower chlorophyll color, but higher biomass concentration
      and lipid accumulation rate. The present results revealed that CRISPRi based
      transcriptional silencing was applicable in C. reinhardtii and expanded the way
      to improve the yield, titer and productivity of microalgae-based products.

PMID- 28501381
TI  - Salinity induced oxidative stress alters the physiological responses and improves
      the biofuel potential of green microalgae Acutodesmus dimorphus.
AB  - The main aim of the present study was to analyze salinity stress induced
      physiological and biochemical changes in a freshwater microalgae Acutodesmus
      dimorphus. During single-stage cultivation, the accumulations of lipids and
      carbohydrates increased with an increase in an initial salinity of the culture
      medium. The carbohydrate and lipid accumulations of 53.30+/-2.76% and 33.40+/
      2.29%, respectively, were observed in 200mM NaCl added culture. During two-stage
      cultivation, salinity stress of 200mM was favorable for the growth up to 2days,
      as suggested by higher biomass, lower levels of oxidative stress biomarkers and
      no significant changes in the biochemical composition of the cells. Extending the
      stress to 3days significantly increased the lipid accumulation by 43% without
      affecting the biomass production. This study, thus, provides the strategy to
      improve the biofuel potential of A. dimorphus along with presenting the
      physiological adaptive mechanisms of a cell against salinity stress.

PMID- 28501382
TI  - Fabrication of biochars obtained from valorization of biowaste and evaluation of
      its physicochemical properties.
AB  - This study investigated the yields and the physicochemical properties of biochar
      from three different feedstocks viz., i) bioenergy byproducts (deoiled cakes of
      Jatropha carcus and Pongamia glabra), ii) lignocellulose biomass (Jatropha carcus
      seed cover), and iii) a noxious weed (Parthenium hysterophorus), obtained through
      slow pyrolysis at a heating rate of 40 degrees Cmin-1 with a nitrogen flow
      100mlmin-1 at a temperature range of 350-650 degrees C. For successful
      utilization of biochar for C-sequestration, its ability to resist abiotic or
      biotic degradation was deduced from recalcitrance index R50 by using TG analysis.
      It was observed that the biochar produced at higher temperature had higher water
      holding capacity (WHC) and pH, suggesting its suitability as an amendment in soil
      with low water retention capacity; thus biochar may be designed to selectively
      improve soil chemical and physical properties by altering feedstocks and
      pyrolysis conditions. Biochar produced at 650 degrees C had highest yield in the
      range of 28.52-39.9 wt.%.

PMID- 28501383
TI  - Intentional Misuse and Abuse of Loperamide: A New Look at a Drug with "Low Abuse
      Potential".
AB  - BACKGROUND: Despite its opioid properties, loperamide has long been thought to
      have low abuse potential due to its poor absorption from the gastrointestinal
      tract and limited potential to cross the blood-brain barrier. A recent patient
      reportedly taking loperamide to avoid heroin withdrawal symptoms, at doses
      approximately 100 times those recommended, directed our attention to this issue.
      OBJECTIVES: 1) Investigate number of cases of intentional loperamide abuse and
      misuse reported to poison centers between 2009 and 2015; 2) Compile reports of
      clinical effects of loperamide abuse; and 3) Search for evidence of increasing
      Internet interest in the central opioid effects of loperamide. METHODS: For the
      years 2009 thru 2015, we reviewed exposure calls related to misuse/abuse of
      loperamide in the Texas Poison Center Network's database and the National Poison
      Data System. We used Google trend analysis to detect evidence of increased
      Internet interest in the illicit use of loperamide. RESULTS: Between 2009 and
      2015, the number of misuse/abuse calls related to loperamide alone nearly
      doubled, with about one-third of cases occurring in teens and young adults in
      their 20s. Of particular concern are reports of significant cardiotoxic effects
      (~18% of cases), including conduction defects and various dysrhythmias, sometimes
      leading to death. Google Trends analysis demonstrates an increasing number of
      searches for "loperamide high" and "loperamide withdrawal" beginning in 2011.
      CONCLUSIONS: Loperamide misuse/abuse seems to be on the rise. Given its
      propensity to induce conduction disturbances and dysrhythmias at very high doses,
      emergency physicians should be vigilant for this form of drug abuse.

PMID- 28501384
TI  - Acute Heart Failure in the Emergency Department: the SAFE-SIMEU Epidemiological
      Study.
AB  - BACKGROUND: Patients with acute heart failure (AHF) have high rates of attendance
      to emergency departments (EDs), with significant health care costs. OBJECTIVES:
      We aimed to describe the clinical characteristics of patients attending Italian
      EDs for AHF and their diagnostic and therapeutic work-up. METHODS: We carried out
      a retrospective analysis on 2683 cases observed in six Italian EDs for AHF
      (January 2011 to June 2012). RESULTS: The median age of patients was 84 years
      (interquartile range 12), with females accounting for 55.8% of cases (95%
      confidence interval [CI] 53.5-57.6%). A first episode of AHF was recorded in
      55.3% (95% CI 55.4-57.2%). Respiratory disease was the main precipitating factor
      (approximately 30% of cases), and multiple comorbidities were recorded in > 50%
      of cases (history of acute coronary syndrome, chronic obstructive pulmonary
      disease, diabetes, chronic kidney disease, valvular heart disease). The treatment
      was based on oxygen (69.7%; 67.9-71.5%), diuretics (69.2%; 67.9-71.5%),
      nitroglycerin (19.7%; 18.3-21.4%), and noninvasive ventilation (15.2%; 13.8
      16.6%). Death occurred within 6 h in 2.5% of cases (2.0-3.1%), 6.4% (5.5-7.3%)
      were referred to the care of their general practitioners within a few hours from
      ED attendance or after short-term (< 24 h) observation 13.9% (12.6-15.2%); 60.4%
      (58.5-62.2%) were admitted to the hospital, and 16.8% (15.4-18.3%) were cared for
      in intensive care units according to disease severity. CONCLUSIONS: Our study
      reporting the "real-world" clinical activity indicates that subjects attending
      the Italian EDs for AHF are rather different from those reported in international
      registries. Subjects are older, with a higher proportion of females, and high
      prevalence of cardiac and noncardiac comorbidities.

PMID- 28501385
TI  - Full and Partial Thickness Burns from Spontaneous Combustion of E-Cigarette
      Lithium-Ion Batteries with Review of Literature.
AB  - BACKGROUND: In recent years, the use of electronic cigarettes (e-cigarettes) has
      increased worldwide. Most electronic nicotine delivery systems use rechargeable
      lithium-ion batteries, which are relatively safe, but in rare cases these
      batteries can spontaneously combust, leading to serious full and partial
      thickness burn injuries. Explosions from lithium-ion batteries can cause a flash
      fire and accelerant-related burn injuries. CASE REPORT: A retrospective chart
      review was conducted of 3 patients with lithium-ion battery burns seen at our
      Level I community-based trauma center. Clinical presentation, management, and
      outcome are presented. All 3 patients sustained burn injuries (total body surface
      area range 5-13%) from the spontaneous combustion of lithium-ion batteries used
      for e-cigarettes. All patients were treated with debridement and local wound
      care. All fully recovered without sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE
      AWARE OF THIS?: Emergency physicians can expect to treat burn cases due to
      spontaneous lithium-ion battery combustion as e-cigarette use continues to
      increase. The cases presented here are intended to bring attention to lithium-ion
      battery-related burns, prepare physicians for the clinical presentation of this
      burn mechanism, and facilitate patient education to minimize burn risk.

PMID- 28501386
TI  - Atrioesophageal Fistula after Ablation for Atrial Fibrillation.
AB  - BACKGROUND: Atrioesophageal fistula (AEF) is a rare and highly fatal complication
      of ablation procedures for atrial fibrillation. We report a diagnostically
      challenging case of AEF that highlights the unfortunate outcome that can be
      expected when this condition is not promptly diagnosed and managed accordingly.
      The varied clinical presentations are reviewed and recommended diagnostic and
      management approaches are presented. CASE REPORT: A 79-year-old female who was 5
      weeks post-ablation presented to a community emergency department with chest pain
      and a transient episode of left-arm weakness. Troponin was mildly elevated, but
      other investigations, including thoracic and head computed tomography (CT) were
      normal. During the course of the next few days in hospital, the diagnosis of AEF
      became apparent, as the patient developed a fever and recurrent episodes of
      neurologic deficits along with blood cultures that yielded upper gastrointestinal
      flora. The patient was urgently transferred to a tertiary center where repeat
      thoracic CT confirmed the diagnosis, but she succumbed to an intracranial bleed
      before definitive surgical management could be performed. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: This case is presented to increase awareness among
      emergency physicians of this fatal condition that is increasing in incidence as
      ablation procedures become more mainstream. The diagnosis can be challenging,
      given that presenting symptoms are often variable and nonspecific. To complicate
      matters further, performing certain diagnostic tests and interventions can prove
      fatal in this particular patient population. Survival in these unfortunate cases
      is highly dependent on initiating a prompt and appropriate diagnostic workup,
      followed by rapid surgical intervention.

PMID- 28501387
TI  - Surgical treatment of isolated zygomatic fracture: Outcome comparison between
      titanium plate and bioabsorbable plate.
AB  - BACKGROUND: Zygoma fracture is of clinical importance because malar prominence
      plays an essential role in facial appearance. Traditionally, most maxillofacial
      surgeons perform osteosynthesis with titanium plates and screws for rigid
      fixation. However, this procedure has certain disadvantages that include the
      possibility of implant exposure, palpability or loosening of the screws, painful
      irritation, temperature sensitization, and radiographic artifacts. In this study,
      we compared the function and satisfaction outcome between Bonamates(r)
      bioabsorbable implant and Leibinger titanium implant. METHOD: Consecutively 53
      patients with isolated unilateral zygomatic fracture that were treated with the
      Bonamates(r) bioabsorbable plate system, n = 53 were compared to patients with
      the titanium plate system, n = 55 in the period between 2009 and 2013. All
      patients were followed-up at least 6 months. Preoperative and postoperative
      facial computed tomography (CT) scans were performed and scored from 0 to 2 in
      the 5 areas of zygoma. A score of 2 indicated the most severely displaced
      fracture in one of the areas. A visual analogue scale ranging from 0 to 10 was
      used to assess the postoperative aesthetic and functional satisfactions. RESULT:
      The mean ages of the patients in the bioabsorbable and titanium plate groups were
      33 years and 30 years, respectively. The male to female ratios were 1.2:1
      (bioabsorbable plate group) and 1.1:1 (titanium plate group). The average
      preoperative CT scan scores of the bioabsorbable and titanium plate groups were
      5.7 and 5.1, respectively. The postoperative CT scan scores of the bioabsorbable
      and titanium plate groups were 1.3 and 1.1, respectively. The implant cost of the
      bioabsorbable group was approximately 6-fold higher than that of the titanium
      plate group. The complication rate was similar in both groups and included
      complications such as palpable implant, skin irritation, and hypersensitive
      cheek. The patients in both groups attained similar mouth-opening function and a
      satisfactory score at 6 months after operation. CONCLUSION: This study revealed
      that the bioabsorbable plate outcome was similar to the titanium plate outcome
      for patients with isolated unilateral zygomatic fracture. The bioabsorbable
      implant system provides another option for internal fixation devices in the
      treatment of zygomatic fractures and avoids implant removal surgery; however, the
      implant cost of bioabsorbable plates is higher than that of titanium plates in
      Taiwan.

PMID- 28501388
TI  - Association between metabolic syndrome and chronic kidney disease in a Chinese
      urban population.
AB  - BACKGROUND: Few studies have examined the relationships between the prevalence of
      chronic kidney disease (CKD) and the metabolic risk factors in a developing
      country such as China, where genetic and environmental backgrounds differ from
      those in Western countries. METHODS: The subjects of this cross-sectional study
      were the individuals from 18 to 92y. The metabolic syndrome (MetS) was defined
      based on the criteria of Adult Treatment Panel Third Report (ATP III), but using
      body mass index (BMI) instead of waist circumference. CKD was defined as
      decreased estimated glomerular filtration rate (eGFR<60mL/min/1.73m2) or presence
      of proteinuria (urine protein>=1+) assessed using dipstick method. RESULTS: A
      total of 26,601 subjects (average age of 48.7y) were analyzed. Among them, the
      prevalence of the MetS and CKD was 36.4% and 3.0%, respectively. After adjustment
      for age, gender, cigarette smoking and alcohol drinking, the prevalence of CKD
      was significantly greater in subjects with than without MetS (OR 1.99, 95% CI
      1.57-2.53, p<0.001). Multivariate-adjusted odd ratios for CKD in subjects with 3,
      4 or 5 MetS components were 1.82 (95% CI 1.31-2.52, p<0.001), 2.92 (95% CI 2.09
      4.09, p<0.001), and 3.07 (95% CI 1.67-5.67, p<0.001), respectively. After further
      adjustments were made for the other components of MetS, only high fasting glucose
      (OR 1.52, 95% CI 1.12-2.05) were significant risk factors for reduced renal
      function(eGFR<60mL/min/1.73m2). High blood pressure (OR 1.81, 95% CI 1,42-2.29),
      high triglycerides (OR 1.34, 95% CI 1.11-1.67) and high fasting glucose (OR 2.07,
      95% CI 1.62-2.66) were significant risk factors for proteinuria. CONCLUSIONS:
      MetS was highly prevalent in the middle-aged and elderly Chinese population in
      the city of Jinan. There was a graded relationship between the number of MetS
      components and risk of CKD. High fasting blood glucose levels were the main risk
      factor of reduced renal function. High blood pressure, high fasting blood glucose
      levels and high triglycerides were main risk factors for proteinuria.

PMID- 28501389
TI  - Differential proteome profile in ischemic heart disease: Prognostic value in
      chronic angina versus myocardial infarction. A proof of concept.
AB  - The initial clinical manifestation of ischemic heart disease (IHD) i.e.
      unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is
      statistically associated with adverse or mild disease progression respectively in
      the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic
      analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass
      Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic
      biomarkers of IHD manifestation. We found several differentially expressed peaks
      but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively)
      were most reliable. Two of them were identified; 14,158m/z peak was the double
      charged form of Apolipoprotein A-I and its vasoprotective action accords with
      prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither
      the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude
      that SELDI-TOF-MS analysis may yield a panel of molecular signals able to
      retrospectively classify patients according to their clinical and molecular
      features, exploitable for predicting the natural course of IHD.

PMID- 28501390
TI  - Clinical Features and Incidence Rates of Ocular Complications in Patients With
      Retinal Vasculitis.
AB  - PURPOSE: To describe the incidence rates of visual loss and ocular complications
      in patients with retinal vasculitis (RV). DESIGN: Retrospective cohort study.
      METHODS: Clinical data were collected for 96 patients (175 eyes) diagnosed with
      RV from 2003 to 2013. Main outcome measures included rates of visual loss and
      ocular complications. Comparison of outcomes in patients with a relapsing vs
      nonrelapsing disease also were analyzed. RESULTS: Over a median follow-up of 44
      months (range: 1-153 months), the rate of visual loss to 20/50 or worse was 0.13
      per eye-year (/EY, 95% confidence interval [CI], 0.09/EY to 0.18/EY) and to
      20/200 or worse was 0.06/EY (95% CI, 0.04/EY to 0.08/EY). The most common
      complications were cataract (0.31/EY), epiretinal membrane (0.16/EY), and
      recurrent macular edema (0.09/EY). Patients with a relapsing course (median
      number of relapses = 1, range: 1-6) appeared to have greater risk for visual loss
      to 20/50 (odds ratio [OR] = 2.07; 95% CI, 0.88-4.90, P = .09) and 20/200 or worse
      (OR = 2.49; 95% CI, 0.98-6.30, P = .05). Immunosuppressive drug therapy lowered
      the risk of visual loss, independent of relapsing disease course (OR = 0.79; 95%
      CI, 0.66-0.94, P = .01 and OR = 0.73; 95% CI, 0.57-0.93, P = .01 for the 20/50 or
      worse and 20/200 or worse thresholds, respectively). CONCLUSIONS: Rates of visual
      loss and complications among patients with RV were similar to reported rates in
      noninfectious uveitides. Treatment with immunosuppressive drugs lowered the risk
      of visual loss. A relapsing course suggested an increased risk for visual loss
      but was not statistically significant, perhaps owing to low numbers of
      recurrences.

PMID- 28501391
TI  - Long-term Visual Acuity, Strabismus, and Nystagmus Outcomes Following
      Multimodality Treatment in Group D Retinoblastoma Eyes.
AB  - PURPOSE: To analyze the long-term visual acuity, strabismus, and nystagmus
      outcomes in Group D retinoblastoma following multimodality treatments in a
      national retinoblastoma referral center. DESIGN: Retrospective interventional
      case series. METHODS: A 13-year retrospective chart review of Group D eyes
      treated initially with intravenous chemotherapy (IVC) and followed up for at
      least 1 year from last treatment. Risk factors for final visual acuity (VA) were
      analyzed, and rate of strabismus and nystagmus at last follow-up visit were
      calculated. RESULTS: One hundred and four Group D eyes (92 patients) presented to
      our center during the study period, of which 32 (27 patients) met the inclusion
      criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant
      treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque
      brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and
      cryotherapy in 24 (75%) eyes. On last examination, 64.41 +/- 6.76 months from
      presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 +/- 0.15). On
      univariate analysis, presentation age, foveal retinoblastoma (at initial
      examination), use of TTT, and tumor-foveola distance (at last visit) were found
      to be significant risk factors for worse VA (P < .026). On multivariate analysis,
      however, only TTT was found to be significant (P = .010). At last visit, 6 of 27
      (22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had
      strabismus (n = 10 exotropia and n = 2 esotropia). CONCLUSIONS: After
      multimodality treatments initiated with IVC, 50% of salvaged Group D
      retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse
      vision; 60% had strabismus; and 22% had nystagmus.

PMID- 28501392
TI  - Acute Retinal Necrosis: Presenting Characteristics and Clinical Outcomes in a
      Cohort of Polymerase Chain Reaction-Positive Patients.
AB  - PURPOSE: To identify determinants of adverse outcomes in acute retinal necrosis
      (ARN), presenting characteristics and incidence rates of vision loss and ocular
      complications in a cohort of polymerase chain reaction (PCR)-positive eyes were
      analyzed. DESIGN: Retrospective observational cohort study. METHODS: Forty-one
      eyes of 36 patients with clinically diagnosed ARN, PCR-positive for herpes
      simplex virus or varicella zoster virus and evaluated between January 2002 and
      June 2013, were included. Main outcome measures included incidence rates of
      vision loss and retinal detachment (RD). RESULTS: Presenting visual acuity was
      generally poor (20/50 to >20/200 in 27%; 20/200 or worse in 56%). The incidence
      rate of <=20/200 was 0.66/eye-year (EY), (95% confidence interval [CI], 0.32/EY
      to 1.22/EY); the rate of light perception or no light perception vision was
      0.07/EY (95% CI, 0.02/EY to 0.16/EY). During follow-up, 59% of eyes developed at
      least 1 RD (rate = 0.40/EY, 95% CI, 0.19/EY to 0.58/EY). Eyes with retinitis
      involving >=25% of the retina at presentation detached at nearly 12 times the
      rate, as compared to those with <25% retinal involvement (0.70/EY vs 0.06/EY; P =
      .001). Development of an RD was the greatest determinant of adverse visual
      outcomes, with 4% of eyes, that had experienced at least 1 RD, achieving a best
      corrected visual acuity of >=20/40 compared to 53% of eyes that never detached (P
      = .0003). CONCLUSIONS: Poor outcomes in ARN were common in this cohort. RD
      confers the greatest risk of incident vision loss, and once 25% or more of the
      retina is involved the risk of RD and visual loss increases significantly.

PMID- 28501393
TI  - Seq-ing the Circuit Logic of the Basal Ganglia.
AB  - Recently, Wallace et al. (2017) provide an unprecedented view of the layers of
      molecular, cellular and circuit complexity involving a basal ganglia output
      structure, the entopeduncular nucleus. Their findings lend order to chaos by
      revealing how molecularly and functionally defined cellular subsets are organized
      into distinct circuitry.

PMID- 28501394
TI  - [Changes in hazardous drinking in Spanish adolescent population in the last
      decade (2004-2013) using a quantitative and qualitative design].
AB  - OBJECTIVE: To determine the changes in hazardous drinking in adolescents in the
      last decade, as well as their motivations and experiences. DESIGN: Firstly, a
      descriptive design using a self-report questionnaire, and secondly an explanatory
      qualitative design, with video recordings of discussion groups with content
      analysis (coding, triangulation of categories and verification of results).
      SETTING AND PARTICIPANTS: Pupils from an urban High School, administering a
      questionnaire every 3 years from 2004 to 2013. Purposive sampling was used to
      elect groups in qualitative design. Homogeneity criteria: education level;
      heterogeneity criteria: age, gender, and drug use. MAIN MEASUREMENTS:
      Questionnaire: age, gender, drug use, and the CAGE test. Interviews: semi
      structured on a previous script, evaluating experiences and expectations.
      RESULTS: Descriptive design: A total of 1,558 questionnaires, age 14.2+/
      0.3years, 50% female. The prevalence of alcohol drinking decreases (13%), but its
      hazardous use increases (11%; P<.001, chi2). This is associated with being female
      (P<.01 chi2), higher alcohol consumption (>6 standard drink units weekly; P<.001,
      ANOVA), during the weekend (56%; P<.01, chi2) and multiple drug use (P<.01,
      chi2). CAGE questionnaire: 37% >=1positive response (related to hazardous
      drinking, P<.05 chi2), 18% >=2answers. QUALITATIVE: A total of 48 respondents,
      classified into 4 categories: personal factors (age, gender), social influences
      (family, friends), consumption standards (accessibility, nightlife), and
      addiction (risk, multiple drug use). CONCLUSION: Despite the decrease in the
      prevalence of alcohol drinking, the increase in the percentage of the hazardous
      drinking is a public health problem. It is related to being female, binge
      drinking, and multiple drug use. Nightlife and social standards are the main
      reasons given by adolescents, who have no perception of risk.

PMID- 28501395
TI  - [Acceptability and feasibility among primary care doctors of the opportunistic
      search for HIV in Health Care centers in Spain].
AB  - OBJECTIVE: To evaluate the acceptability and feasibility of the opportunistic
      search of HIV according to primary care doctors' experience. To set up the
      profile of the physician involved in this study. DESIGN: Observational,
      transversal study. LOCATION: Primary Care Centers of the National Health System.
      PARTICIPANTS: General practitioners and residents who participated in VIH-AP
      study to measure the acceptability of HIV opportunistic search by patients. MAIN
      MEASUREMENTS: Self-filling survey to collect data on age, sex, teaching skills,
      amount of years dedicated to research, time working with the same quota of
      patients, acceptability and feasibility of opportunistic HIV search. RESULTS: A
      total of 197 physicians with a mean age of 45.2+/-9.7 (SD) years. 18.8% were
      under 36years old, 70.1% were women and 62.4% had teaching skills. 55.8% worked
      in towns with a population over 100,000 inhabitants and the mean of years working
      with the same quota of patients was 6.4+/-6.6. 91.9% (95%CI: 88.1-98.7) of them
      considered the opportunistic search of HIV acceptable and 89.3% (95%CI: 85.0
      93.6), feasible to perform. The multivariate analysis showed positive relation
      between the acceptability/feasibility and teaching skills (OR: 2.74; 95%CI: 1.16
      6.49). The acceptance of the screening by patients was 93.1% and this was
      positively related to how long the doctor had worked with the same quota,
      teaching skills and the amount of years dedicated to research. CONCLUSIONS: HIV
      opportunistic search is an acceptable and feasible method for primary care
      professionals.

PMID- 28501396
TI  - Analysis of copy number variations in Holstein-Friesian cow genomes based on
      whole-genome sequence data.
AB  - Thirty-two whole genome DNA sequences of cows were analyzed to evaluate inter
      individual variability in the distribution and length of copy number variations
      (CNV) and to functionally annotate CNV breakpoints. The total number of deletions
      per individual varied between 9,731 and 15,051, whereas the number of
      duplications was between 1,694 and 5,187. Most of the deletions (81%) and
      duplications (86%) were unique to a single cow. No relation between the pattern
      of variant sharing and a family relationship or disease status was found. The
      animal-averaged length of deletions was from 5,234 to 9,145 bp and the average
      length of duplications was between 7,254 and 8,843 bp. Highly significant inter
      individual variation in length and number of CNV was detected for both deletions
      and duplications. The majority of deletion and duplication breakpoints were
      located in intergenic regions and introns, whereas fewer were identified in
      noncoding transcripts and splice regions. Only 1.35 and 0.79% of the deletion and
      duplication breakpoints were observed within coding regions. A gene with the
      highest number of deletion breakpoints codes for protein kinase cGMP-dependent
      type I, whereas the T-cell receptor alpha constant gene had the most duplication
      breakpoints. The functional annotation of genes with the largest incidence of
      deletion/duplication breakpoints identified 87/112 Kyoto Encyclopedia of Genes
      and Genomes pathways, but none of the pathways were significantly enriched or
      depleted with breakpoints. The analysis of Gene Ontology (GO) terms revealed that
      a cluster with the highest enrichment score among genes with many deletion
      breakpoints was represented by GO terms related to ion transport, whereas the GO
      term cluster mostly enriched among the genes with many duplication breakpoints
      was related to binding of macromolecules. Furthermore, when considering the
      number of deletion breakpoints per gene functional category, no significant
      differences were observed between the "housekeeping" and "strong selection"
      categories, but genes representing the "low selection pressure" group showed a
      significantly higher number of breakpoints.

PMID- 28501397
TI  - Effect of conjugated linoleic acid and acetate on milk fat synthesis and adipose
      lipogenesis in lactating dairy cows.
AB  - During biohydrogenation-induced milk fat depression (MFD), nutrients are spared
      from milk fat synthesis and are available for other metabolic uses. Acetate is
      the major carbon source spared and it may increase lipid synthesis in adipose
      tissue during MFD. The objective of this study was to compare the effect of trans
      10,cis-12 conjugated linoleic acid (CLA) and the amount of acetate spared during
      CLA-induced MFD on adipose tissue lipogenesis. Nine multiparous, lactating,
      ruminally cannulated Holstein cows (244 +/- 107 d in milk; 25 +/- 8.4 kg of
      milk/d; mean +/- standard deviation) were randomly assigned to treatments in a 3
      * 3 Latin square design. Experimental periods were 4 d followed by a 10-d
      washout. Treatments were control (CON), ruminal infusion of acetate (AC;
      continuous infusion of 7 mol/d adjusted to pH 6.1 with sodium hydroxide), or
      abomasal infusion of CLA (10 g/d of both trans-10,cis-12 CLA and cis-9,trans-11
      CLA). Dry matter intake, milk yield, and milk protein yield and percentage were
      not affected by treatments. Compared with CON, milk fat yield decreased 23% and
      fat percent decreased 28% in CLA, and milk fat yield increased 20% in AC.
      Concentration and yield of milk de novo synthesized fatty acids (<C16) were
      reduced and concentration of preformed fatty acids (>C16) was increased by CLA,
      compared with CON. Yield of de novo synthesized fatty acids and palmitic acid was
      increased by AC, compared with CON. Lipogenesis capacity of adipose tissue
      explants was decreased 72% by CLA, but was not affected by AC. Acetate oxidation
      by adipose explants was not affected by treatments. Treatments had no effect on
      expression of key lipogenic factors, lipogenic enzymes, and leptin; however,
      expression of fatty acid binding protein 4 was reduced in CLA compared with CON.
      Additionally, hormone-sensitive lipase and perilipin 1 were decreased by CLA and
      acetate. Plasma glucose and glucagon concentrations were not affected by
      treatments; however, CLA increased nonesterified fatty acids 17.7%, beta
      hydroxybutyrate 16.1%, and insulin 27.8% compared with CON, and AC increased
      plasma beta-hydroxybutyrate 18%. In conclusion, during CLA-induced MFD in low
      producing cow adipose tissue was sensitive to the anti-lipogenic effects of CLA,
      while spared acetate did not stimulate adipose lipogenesis. However, acetate may
      play an important role in stimulating lipogenesis and improving energy status in
      the mammary gland under normal conditions.

PMID- 28501398
TI  - Machine-learning-based calving prediction from activity, lying, and ruminating
      behaviors in dairy cattle.
AB  - The objective of this study was to use automated activity, lying, and rumination
      monitors to characterize prepartum behavior and predict calving in dairy cattle.
      Data were collected from 20 primiparous and 33 multiparous Holstein dairy cattle
      from September 2011 to May 2013 at the University of Kentucky Coldstream Dairy.
      The HR Tag (SCR Engineers Ltd., Netanya, Israel) automatically collected neck
      activity and rumination data in 2-h increments. The IceQube (IceRobotics Ltd.,
      South Queensferry, United Kingdom) automatically collected number of steps, lying
      time, standing time, number of transitions from standing to lying (lying bouts),
      and total motion, summed in 15-min increments. IceQube data were summed in 2-h
      increments to match HR Tag data. All behavioral data were collected for 14 d
      before the predicted calving date. Retrospective data analysis was performed
      using mixed linear models to examine behavioral changes by day in the 14 d before
      calving. Bihourly behavioral differences from baseline values over the 14 d
      before calving were also evaluated using mixed linear models. Changes in daily
      rumination time, total motion, lying time, and lying bouts occurred in the 14 d
      before calving. In the bihourly analysis, extreme values for all behaviors
      occurred in the final 24 h, indicating that the monitored behaviors may be useful
      in calving prediction. To determine whether technologies were useful at
      predicting calving, random forest, linear discriminant analysis, and neural
      network machine-learning techniques were constructed and implemented using R
      version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). These
      methods were used on variables from each technology and all combined variables
      from both technologies. A neural network analysis that combined variables from
      both technologies at the daily level yielded 100.0% sensitivity and 86.8%
      specificity. A neural network analysis that combined variables from both
      technologies in bihourly increments was used to identify 2-h periods in the 8 h
      before calving with 82.8% sensitivity and 80.4% specificity. Changes in behavior
      and machine-learning alerts indicate that commercially marketed behavioral
      monitors may have calving prediction potential.

PMID- 28501399
TI  - Effect of feeding strategies and cropping systems on greenhouse gas emission from
      Wisconsin certified organic dairy farms.
AB  - Organic agriculture continues to expand in the United States, both in total
      hectares and market share. However, management practices used by dairy organic
      producers, and their resulting environmental impacts, vary across farms. This
      study used a partial life cycle assessment approach to estimate the effect of
      different feeding strategies and associated crop production on greenhouse gas
      emissions (GHG) from Wisconsin certified organic dairy farms. Field and livestock
      driven emissions were calculated using 2 data sets. One was a 20-yr data set from
      the Wisconsin Integrated Cropping System Trial documenting management inputs,
      crop and pasture yields, and soil characteristics, used to estimate field-level
      emissions from land associated with feed production (row crop and pasture),
      including N2O and soil carbon sequestration. The other was a data set summarizing
      organic farm management in Wisconsin, which was used to estimate replacement
      heifer emission (CO2 equivalents), enteric methane (CH4), and manure management
      (N2O and CH4). Three combinations of corn grain (CG) and soybean (SB) as
      concentrate (all corn = 100% CG; baseline = 75% CG + 25% SB; half corn = 50% CG +
      50% SB) were assigned to each of 4 representative management strategies as
      determined by survey data. Overall, GHG emissions associated with crop production
      was 1,297 +/- 136 kg of CO2 equivalents/t of ECM without accounting for soil
      carbon changes (DeltaSC), and GHG emission with DeltaSC was 1,457 +/- 111 kg of
      CO2 equivalents/t of ECM, with greater reliance on pasture resulting in less
      DeltaSC. Higher levels of milk production were a major driver associated with
      reduction in GHG emission per metric tonne of ECM. Emissions per metric tonne of
      ECM increased with increasing proportion of SB in the ration; however, including
      SB in the crop rotation decreased N2O emission per metric tonne of ECM from
      cropland due to lower applications of organically approved N fertility inputs.
      More SB at the expense of CG in the ration reduced enteric CH4 emission per
      metric tonne of ECM (because of greater dietary fat content) but increased N2O
      emission per metric tonne of ECM from manure (because of greater N content). An
      increased reliance on pasture for feed at the expense of grain resulted in
      decreased in milk production, subsequently leading to substantially higher
      emissions per metric tonne of ECM.

PMID- 28501400
TI  - The genetics of antibody response to paratuberculosis in dairy cattle.
AB  - Genetic parameters were estimated for antibody response to paratuberculosis
      (Mycobacterium avium ssp. paratuberculosis) using milk ELISA test results,
      collected and analyzed by National Milk Records, from Holstein Friesian cows on
      UK dairy farms in their first 3 lactations. Milk ELISA test results were obtained
      from 2007 to 2012 and combined with milk recording data and pedigree information.
      The reduced data set edited for the purposes of genetic parameter estimation
      consisted of 148,054 milk ELISA records from 64,645 lactations in 40,142 cows of
      908 sires, recorded in 641 herds. Milk ELISA test results were loge-transformed
      and univariate analysis of 3 alternative animal models and equivalent sire models
      were considered. The most appropriate model included additive genetic and
      permanent environmental random effects, whereas maternal effects were significant
      according to likelihood ratio test and Akaike's information criterion but not for
      Bayesian information criterion. Heritability and repeatability estimates were
      0.06 and 0.37, respectively, for the chosen animal model and its equivalent sire
      model. A subset of the data including herds with greater than 10% positive tests
      gave a slightly higher heritability of 0.08. Favorable but generally low
      significant genetic correlations were obtained between antibody response with 305
      d milk yield (-0.16), 305-d protein yield (-0.16), loge-transformed lactation
      average somatic cell count (0.15), and the number of mastitis episodes (0.22).
      Thus, selection on the antibody response to paratuberculosis, should not be
      detrimental to production or udder health traits. Testing cattle for
      paratuberculosis is important for its use in control programs and although the
      heritability of antibody response was low, breeding against the disease might be
      a good prospect as a preventative measure to assist together with other
      approaches in an overall control strategy.

PMID- 28501401
TI  - Milk production and composition, nitrogen utilization, and grazing behavior of
      late-lactation dairy cows as affected by time of allocation of a fresh strip of
      pasture.
AB  - Eighty late-lactation dairy cows were used to examine the effects of allocating a
      new pasture strip of a sward based on ryegrass (Lolium perenne L.) in the morning
      (a.m.; ~0730 h) or in the afternoon (p.m.; ~1530 h) on milk production and
      composition, nitrogen (N) utilization, and grazing behavior. Cows grazed the same
      pasture strips for 24 h and were offered the same daily herbage allowance.
      Herbage composition differed among treatments; p.m. herbage had greater dry
      matter (DM; 22.7 vs. 19.9%), organic matter (OM; 89.5 vs. 88.9%), and water
      soluble carbohydrate (10.9 vs. 7.6%) concentrations and lesser crude protein
      (20.5 vs. 22.2%) and neutral detergent fiber (48.8 vs. 50.4%) concentrations
      compared with a.m. herbage. Total fatty acids (FA), alpha-linolenic acid, and
      polyunsaturated FA (PUFA) were greater in a.m. herbage, whereas monounsaturated
      FA were greater in p.m. herbage. Estimates of herbage DM intake did not differ
      among treatments. Daily milk yields and milk fat and milk protein concentrations
      were similar among treatments, whereas milk fat (684 vs. 627 g/cow), milk protein
      (545 vs. 505 g/cow), and milk solids (milk fat + milk protein) yields (1,228 vs.
      1,132 g/cow) tended to be greater for cows on p.m. herbage. Rumenic acid and
      total PUFA in milk were greater for cows on a.m. herbage, whereas oleic acid was
      greater for cows on p.m. herbage. Estimates of urinary N excretion (g/d) did not
      differ among treatments, but urinary N concentrations were greater for cows on
      a.m. herbage (5.85 vs. 5.36 g/L). Initial herbage mass (HM) available (kg of
      DM/ha) and instantaneous HM disappearance rates (kg of DM/ha and kg of DM/h) did
      not differ, but fractional disappearance rates (0.56 vs. 0.74 per hour for a.m.
      vs. p.m., respectively) differed. Under the current conditions, timing of pasture
      strip allocation altered the herbage nutrient supply to cows; allocating a fresh
      strip of pasture later in the day resulted in moderate increases in milk and milk
      solids yields in late-lactation dairy cows. Conversely, a greater concentration
      of precursor FA in a.m. herbage resulted in a greater concentration of beneficial
      FA in milk, compared with cows on p.m. herbage.

PMID- 28501402
TI  - Thiamine supplementation facilitates thiamine transporter expression in the rumen
      epithelium and attenuates high-grain-induced inflammation in low-yielding dairy
      cows.
AB  - An experiment was conducted to uncover the effects of increasing dietary grain
      levels on expression of thiamine transporters in ruminal epithelium, and to
      assess the protective effects of thiamine against high-grain-induced inflammation
      in dairy cows. Six rumen-fistulated, lactating Holstein dairy cows (627 +/- 16.9
      kg of body weight, 180 +/- 6 d in milk; mean +/- standard deviation) were
      randomly assigned to a replicated 3 * 3 Latin square design trial. Three
      treatments were control (20% dietary starch, dry matter basis), high-grain diet
      (HG, 33.2% dietary starch, DM basis), and HG diet supplemented with 180 mg of
      thiamine/kg of dry matter intake. On d 19 and 20 of each period, milk performance
      was measured. On d 21, ruminal pH, endotoxic lipopolysaccharide (LPS), and
      thiamine contents in rumen and blood, and plasma inflammatory cytokines were
      detected; a rumen papillae biopsy was taken on d 21 to determine the gene and
      protein expression of toll-like receptor 4 (TLR4) signaling pathways. The HG diet
      decreased ruminal pH (5.93 vs. 6.49), increased milk yield from 17.9 to 20.2
      kg/d, and lowered milk fat and protein from 4.28 to 3.83%, and from 3.38 to
      3.11%, respectively. The HG feeding reduced thiamine content in rumen (2.89 vs.
      8.97 MUg/L) and blood (11.66 vs. 17.63 MUg/L), and the relative expression value
      of thiamine transporter-2 (0.37-fold) and mitochondrial thiamine pyrophosphate
      transporter (0.33-fold) was downregulated by HG feeding. The HG-fed cows
      exhibited higher endotoxin LPS in rumen fluid (134,380 vs. 11,815 endotoxin
      units/mL), and higher plasma concentrations of lipopolysaccharide binding protein
      and pro-inflammatory cytokines when compared with the control group. The gene and
      protein expression of tumor necrosis factor alpha (TNFalpha), IL1B, and IL6 in
      rumen epithelium increased when cows were fed the HG diet, indicating that local
      inflammation occurred. The depressions in ruminal pH, milk fat, and protein of HG
      fed cows were reversed by thiamine supplementation. Thiamine supplementation
      increased thiamine contents in rumen and blood, and also upregulated the relative
      expression of thiamine transporters compared with the HG group. Thiamine
      supplementation decreased ruminal LPS (49,361 vs. 134,380 endotoxin units/mL) and
      attenuated the HG-induced inflammation response as indicated by a reduction in
      plasma IL6, and decreasing gene and protein expression of pro-inflammatory
      cytokines in rumen epithelium. Western bottling analysis showed that thiamine
      suppressed the protein expression of TLR4 and the phosphorylation of nuclear
      factor kappa B (NFkappaB) unit p65. In conclusion, HG feeding inhibits thiamine
      transporter expression in ruminal epithelium. Thiamine could attenuate the
      epithelial inflammation during high-grain feeding, and the protective effects may
      be due to its ability to suppress TLR4-mediated NFkappaB signaling pathways.

PMID- 28501404
TI  - Effects of dietary crude protein concentration on late-lactation dairy cow
      performance and indicators of nitrogen utilization.
AB  - The objectives of this study were to measure performance responses and to
      evaluate indictors of N utilization in late-lactation cows fed diets with
      incremental reductions in crude protein (CP) concentration. Holstein cows (n =
      128; 224 +/- 54 d in milk) were stratified by parity and days pregnant (86 +/- 25
      d) and randomly assigned to 1 of 16 pens in a randomized complete block design.
      For 3 wk, all cows received a covariate diet containing 16.9% CP [dry matter (DM)
      basis]. For the subsequent 12 wk, pens were randomly assigned to 1 of 4
      treatments that contained 16.2, 14.4, 13.1, or 11.8% CP (DM basis). Diets were
      offered once daily and contained 32.5% corn silage, 32.5% alfalfa silage, 13.5%
      high-moisture corn, and 21.5% concentrate mix. A reduction in dietary CP was
      achieved by replacing soybean meal with soy hulls in the concentrate mix (DM
      basis). Dry matter intake, milk urea N (MUN; mg/dL), and the yield of milk urea N
      (g/d) decreased linearly with dietary CP. Compared with a 16.2% CP diet, a 14.4%
      CP diet did not alter milk yield throughout the study, but the 13.1 and 11.8% CP
      diets reduced milk yield after 4 and 1 wk, respectively. Furthermore, milk
      protein percentage was reduced for all dietary CP less than 16.2%, but this
      negative effect was temporary and disappeared after 7 wk for the 14.4% CP diet.
      In contrast, MUN adjusted to a new steady state within 1 wk for all dietary
      treatments. Modeling quadratic responses with a plateau led to predictions of no
      reduction in fat- and protein-corrected milk (32.6 kg/d) and yields of fat (1.31
      kg/d), lactose (1.49 kg/d), and true protein (1.12 kg/d) until dietary CP
      decreased below 15.5, 15.3, 15.9, and 16.2%, respectively. In this study, MUN and
      the yield of MUN were highly correlated with N intake, milk protein yield, and
      fat- and protein-corrected milk. Surprisingly, N use efficiency (milk protein
      N/intake N) was not correlated with any variables related to N utilization and
      reached an apparent upper limit of approximately 30%. Although this observation
      may be associated with feeding diets deficient in metabolizable protein, late
      lactation cows in this study adjusted to low dietary CP concentration better than
      anticipated as milk production was 2.6, 3.6, 6.4, and 8.0 kg/d higher than
      National Research Council (2001)-predicted metabolizable protein-allowable milk
      for dietary CP of 16.2, 14.4, 13.1, and 11.8%, respectively.

PMID- 28501403
TI  - Use of calcitriol to maintain postpartum blood calcium and improve immune
      function in dairy cows.
AB  - Our objectives were to determine the effects of an injectable formulation of
      calcitriol on mineral metabolism and immune function in postpartum Holstein cows
      that received an acidogenic diet prepartum to minimize hypocalcemia. In
      experiment 1, cows within 6 h of calving received calcitriol (0, 200, or 300 MUg)
      to determine the dose needed to increase plasma concentrations of Ca; 300 MUg was
      sufficient to sustain Ca for at least 3 d. In experiment 2, multiparous cows were
      assigned randomly to receive only vehicle (control, n = 25) or 300 MUg of
      calcitriol (n = 25) subcutaneously within the first 6 h after calving. Blood was
      sampled before treatment and 12 h later, then daily until 15 d in milk (DIM), and
      analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), total Mg (tMg),
      and total P (tP), metabolites, and hormones. Urine was sampled in the first 7 DIM
      and analyzed for concentrations of tCa, tMg, and creatinine. Neutrophil function
      was evaluated in the first week postpartum. Dry matter intake and production
      performance were evaluated for the first 36 DIM. Calcitriol administration
      increased concentrations of calcitriol in plasma within 12 h of application from
      51 to 427 pg/mL, which returned to baseline within 5 d. Concentrations of iCa and
      tCa increased 24 h after treatment with calcitriol. Concentrations of iCa
      (control = 1.08 vs. calcitriol = 1.20 mM), tCa (control = 2.23 vs. calcitriol =
      2.33 mM), and tP (control = 1.47 vs. calcitriol = 1.81 mM) remained elevated in
      cows treated with calcitriol until 3, 5, and 7 DIM, respectively, whereas
      concentration of tMg (control = 0.76 vs. calcitriol = 0.67 mM) was less in
      calcitriol cows than control cows until 3 DIM. Concentrations of parathyroid
      hormone decreased in calcitriol cows compared with control cows (control = 441
      vs. calcitriol = 336 pg/mL). Calcitriol tended to increase plasma concentrations
      of beta-hydroxybutyrate and serotonin, but concentrations of glucose,
      nonesterified fatty acids, and C-telopeptide of type I collagen in plasma did not
      differ between treatments. Cows treated with calcitriol excreted more urinary tCa
      (control = 0.5 vs. calcitriol = 2.1 g/d) and tMg (control = 4.5 vs. calcitriol =
      5.0 g/d) in the first 7 and 2 DIM, respectively, than control cows. Compared with
      control, calcitriol improved the proportion of neutrophils with oxidative burst
      (control = 31.9 vs. calcitriol = 40.6%), mean fluorescence intensity for
      oxidative burst (control = 90,900 vs. calcitriol = 99,746), and mean fluorescence
      intensity for phagocytosis (control = 23,887 vs. calcitriol = 28,080). Dry matter
      intake, yields of milk, and milk components did not differ between treatments.
      Administration of 300 MUg of calcitriol at calving was safe and effective in
      increasing blood concentration of iCa and plasma concentrations of calcitriol,
      tCa, and tP for the first 6 d after treatment, and improved measures of innate
      immune function in early-lactation Holstein cows.

PMID- 28501405
TI  - Short communication: Nutrient consumption patterns of Lactobacillus acidophilus
      KLDS 1.0738 in controlled pH batch fermentations.
AB  - This work focused on elucidating the nutrient consumption patterns of
      Lactobacillus acidophilus to guide the design of media for high-cell-density
      culture. We investigated the nutrient consumption patterns of L. acidophilus KLDS
      1.0738 in chemically defined media in controlled pH batch fermentations. The most
      abundantly consumed amino acids, vitamins, ions, and purines and pyrimidines were
      Glu and Gly, pyridoxine and nicotinamide, K+ and PO43-, and guanine and uracil,
      respectively. The highest consumption rates for amino acids, vitamins, ions, and
      purines and pyrimidines were Asp and Arg, folic acid and pyridoxine, Fe2+ and
      Mn2+, and uracil and thymine, respectively. Furthermore, most of the amino acids,
      as well as guanine, thymine, pyridoxine, folic acid, nicotinamide, Mg2+, PO43-,
      and K+ had the highest bioavailability from the end of the lag growth phase to
      the mid-exponential growth phase. The overall consumption of glucose, adenine
      nucleotides, 2'-deoxyguanosine monohydrate, calcium pantothenate, Fe2+ and Mn2+
      decreased with increasing average growth rate, indicating more effective use of
      these nutritional components at a higher average growth rate, as biomass yield
      based on nutritional component consumption increased. Our findings help to
      formulate complex media for high-cell-density cultivation and provide a
      theoretical basis for L. acidophilus feeding strategies.

PMID- 28501406
TI  - Effect of inhibiting the lactogenic signal at calving on milk production and
      metabolic and immune perturbations in dairy cows.
AB  - During the periparturient period, the abrupt increase in energy demand for milk
      production often induces metabolic and immunological disturbances in dairy cows.
      Our previous work has shown that reducing milk output by milking once a day or
      incompletely in the first few days of lactation reduces these disturbances. The
      aim of this study was to reduce metabolic and immunological disturbances by
      limiting milk production during the first week of lactation by inhibiting the
      lactogenic signal driven by prolactin. Twenty-two fresh cows received 8 i.m.
      injections of the prolactin-release inhibitor quinagolide (QUIN; 2 mg) or water
      as a control (CTL). The first injection was given just after calving, and the
      subsequent 7 injections were given every 12 h. Milk production was measured until
      d 28 after calving. Blood samples were taken from d 1 (calving) to d 5 and then
      on d 7, 10, 14, 21, and 28 to measure concentrations of urea, phosphorus,
      calcium, glucose, nonesterified fatty acids (NEFA), beta-hydroxybutyrate, and
      prolactin. Other blood samples were taken on d 2, 5, 10, and 28 to analyze
      oxidative burst, phagocytosis, and the effect of the serum on the
      lymphoproliferation of peripheral blood mononuclear cells from donor cows. Blood
      prolactin concentration was lower from d 2 to 5 but higher from d 10 to 28 in the
      QUIN cows than in the CTL cows. Milk production was lower from d 2 to 6 in the
      QUIN cows than in the CTL cows (24.3 +/- 6.4 and 34.8 +/- 4.1 kg/d on average,
      respectively). We observed no residual effect of quinagolide on milk production
      after d 6. During the first week of lactation, blood glucose and calcium
      concentrations were higher and beta-hydroxybutyrate concentration was lower in
      the QUIN cows than in the CTL cows. Blood NEFA, urea, and phosphorus
      concentrations were not affected by the treatment. At d 2 and 5, the phagocytosis
      ability of polymorphonuclear leukocytes was not affected by treatment; however,
      quinagolide injection enhanced the proportion of cells that entered oxidative
      burst, The mitogen-induced proliferation of peripheral blood mononuclear cells
      was greater when they were incubated with serum harvested from the CTL cows and
      was negatively correlated with the NEFA concentration in the serum. Reducing the
      prolactin peak at calving was effective in reducing milk production during the
      first week of lactation without compromising the dairy cow's overall
      productivity. Slowing the increase in milk production allowed a more gradual
      transition from pregnancy to lactation and led to a reduction in metabolic stress
      and an improvement in some immune system aspects during this period.

PMID- 28501407
TI  - Amino acid composition of rumen bacteria and protozoa in cattle.
AB  - Because microbial crude protein (MCP) constitutes more than 50% of the protein
      digested in cattle, its AA composition is needed to adequately estimate AA
      supply. Our objective was to update the AA contributions of the rumen microbial
      AA flowing to the duodenum using only studies from cattle, differentiating
      between fluid-associated bacteria (FAB), particle-associated bacteria (PAB), and
      protozoa, based on published literature (53, 16, and 18 treatment means were used
      for each type of microorganism, respectively). In addition, Cys and Met reported
      concentrations were retained only when an adequate protection of the sulfur
      groups was performed before the acid hydrolysis. The total AA (or true protein)
      fraction represented 82.4% of CP in bacteria. For 10 AA, including 4 essential
      AA, the AA composition differed between protozoa and bacteria. The most
      noticeable differences were a 45% lower Lys concentration and 40% higher Ala
      concentration in bacteria than in protozoa. Differences between FAB and PAB were
      less pronounced than differences between bacteria and protozoa. Assuming 33% FAB,
      50% PAB, and 17% of protozoa in MCP duodenal flow, the updated concentrations of
      AA would decrease supply estimates of Met, Thr, and Val originating from MCP and
      increase those of Lys and Phe by 5 to 10% compared with those calculated using
      the FAB composition reported previously. Therefore, inclusion of the contribution
      of PAB and protozoa to the duodenal MCP flow is needed to adequately estimate AA
      supply from microbial origin when a factorial method is used to estimate duodenal
      AA flow. Furthermore, acknowledging the fact that hydrolysis of 1 kg of true
      microbial protein yields 1.16 kg of free AA substantially increases the estimates
      of AA supply from MCP.

PMID- 28501408
TI  - Understanding the gut microbiome of dairy calves: Opportunities to improve early
      life gut health.
AB  - Early gut microbiota plays a vital role in the long-term health of the host.
      However, understanding of these microbiota is very limited in livestock species,
      especially in dairy calves. Neonatal calves are highly susceptible to enteric
      infections, one of the major causes of calf death, so approaches to improving gut
      health and overall calf health are needed. An increasing number of studies are
      exploring the microbial composition of the gut, the mucosal immune system, and
      early dietary interventions to improve the health of dairy calves, revealing
      possibilities for effectively reducing the susceptibility of calves to enteric
      infections while promoting growth. Still, comprehensive understanding of the
      effect of dietary interventions on gut microbiota-one of the key aspects of gut
      health-is lacking. Such knowledge may provide in-depth understanding of the
      mechanisms behind functional changes in response to dietary interventions.
      Understanding of host-microbial interactions with dietary interventions and the
      role of the gut microbiota during pathogenesis at the site of infection in early
      life is vital for designing effective tools and techniques to improve calf gut
      health.

PMID- 28501409
TI  - Effect of different fat supplements on performance of dairy calves during cold
      season.
AB  - The objective of this experiment was to evaluate the effects of starter
      supplementation with fat sources differing in their fatty acid (FA) profile on
      performance of dairy calves during cold season. Sixty Holstein calves (3 d of
      age; 39.7 +/- 3.8 kg of body weight) were randomly assigned to 1 of 5 starter
      diets supplemented with (1) no fat or oil source (control), (2) 3% palm fat
      (PLF), (3) 3% soybean oil (SBO), (4) 3% tallow (TAL), and (5) a 3.2% mixture
      (MIX) of PLF, SBO, and fish oil. The fat supplements were substituted for corn in
      the basal starter diet. Both the control and fat-supplemented diets contained
      similar amounts of dietary crude protein (19.4%), but the latter had a slightly
      higher quantity of calculated metabolizable energy (3.17 vs. 3.07 Mcal/kg) than
      did the former. Calves were reared outdoor in individual pens during the cold of
      winter with a mean ambient temperature of 5.0 degrees C during the study period.
      Whole milk was offered twice daily from d 3 to 45 and once from d 46 to 49. The
      animals were weaned on d 50 and monitored in their individual pens until d 70.
      Supplementation with SBO and MIX increased both the dietary concentration and
      ratio of essential FA (n-6 and n-3), whereas supplementation with TAL and PLF
      made no change in the essential FA profile. Starter intake and average daily gain
      were not affected by PLF and TAL supplements, but were reduced as a result of
      feeding MIX. Feeding supplemental SBO did not affect starter intake, but tended
      to improve average daily gain and final body weight. Fat sources had no effects
      on body skeletal measurements, fecal score, digestibility, ruminal pH, ammonia,
      and total volatile FA concentrations; however, feeding MIX increased rumen molar
      proportion of propionate. No differences were observed in blood metabolites
      across the treatments during the preweaning period. Plasma concentrations of
      triacylglycerol and cholesterol increased when fat sources were supplemented and
      glucose concentration increased when SBO was supplemented during the postweaning
      period. Overall, addition of 3% PLF or TAL to the diet of young calves failed to
      improve growth performance. Although addition of SBO and MIX increased the
      dietary essential FA concentration, calf performance was only improved when SBO
      was supplemented.

PMID- 28501410
TI  - Effects of dietary energy allowance and decline in dry matter intake during the
      dry period on responses to glucose and insulin in transition dairy cows.
AB  - We assessed whether high energy intake during the early dry period [144% of
      metabolizable energy (ME) requirements/d] followed by a gradual restriction of
      energy intake in the close-up dry period (119% of ME/d; HEI) impaired whole-body
      insulin sensitivity compared with a controlled energy intake (100% of ME/d; CEI)
      throughout the 6-wk dry period. Multiparous Ayrshire dairy cows (n = 16) were
      blocked by body weight, body condition score, and expected date of parturition
      and were used in a randomized complete block design until 10 d after parturition.
      Cows were fed either HEI or CEI diets based on grass silage during the first 3 wk
      of the dry period and grass silage supplemented with a commercial concentrate
      (30% of ME intake) during the final 3 wk of gestation. After calving, all cows
      were fed grass silage ad libitum and an increasing amount of commercial
      concentrate (maximum 9 kg at d 10 postpartum). Intravenous glucose tolerance
      tests (IVGTT) and intravenous insulin challenges were performed -10 +/- 5 d (n =
      15) and +10 +/- 1 d (n = 14) relative to parturition. Following glucose
      injection, we did not find any treatment effects on glucose and insulin
      responses. The prepartal nonesterified fatty acid (NEFA) response of the HEI
      group was blunted, basal NEFA and the decrement of NEFA were smaller, and the
      area under the response curve (AUC) of NEFA was less negative in HEI cows than in
      CEI cows. The NEFA response reversed after parturition; the NEFA AUC of the HEI
      group was more negative than that of the CEI group. We did not find similar
      responses after insulin injection. Across the treatments, NEFA AUC correlated
      strongly with the basal NEFA concentration during the IVGTT pre- and postpartum.
      Calculated and model-based indices characterizing the overall glucose tolerance
      and beta-cell function and the insulin sensitivity were higher after parturition
      than during the dry period. Consistent with the lower basal insulin, the acute
      insulin release after the glucose infusion was smaller in postpartal IVGTT than
      in prepartal IVGTT. The results suggest that whole-body insulin sensitivity of
      the cows increased after parturition. However, the role of peripheral insulin
      sensitivity in the regulation of glucose partitioning seems to be minor relative
      to the major change in insulin secretion and clearance during the periparturient
      period.

PMID- 28501412
TI  - Sudden Death in a Diver: A Diagnostic Conundrum.
AB  - We discuss the case of an experienced diver who ran out of air during his final
      ascent while scuba diving. He lost consciousness rapidly after surfacing and
      despite immediate cardiopulmonary resuscitation, could not be revived. On arrival
      at the emergency department he was noted to have copious amounts of blood in his
      upper airway and had developed extensive subcutaneous emphysema. Large amounts of
      air were observed in the central circulation following a postmortem computerized
      tomography scan as well as pneumomediastinum, a small right-sided hemothorax, and
      extensive subcutaneous emphysema. We discuss several potential pathophysiological
      mechanisms that might explain these findings. Finally, we end with a
      recommendation for an expedient whole-body postmortem computerized tomography
      scan and autopsy by a suitably qualified pathologist in the investigation of all
      dive-related fatalities, where possible.

PMID- 28501411
TI  - Short communication: Associations between blood glucose concentration, onset of
      hyperketonemia, and milk production in early lactation dairy cows.
AB  - The objectives of this study were to describe the associations between
      hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of
      lactation, to evaluate the effects of body condition score at calving on glucose
      concentration, and to study the effects of hypoglycemia on milk production. A
      total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled
      between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an
      electronic handheld meter for glucose and beta-hydroxybutyrate (BHB),
      respectively, for a period of 42 d. Hypoglycemia was defined as glucose
      concentration <=2.2 mmol/L. Hyperketonemia was defined as a BHB concentration
      >=1.2 mmol/L. The onset of HYK was described as early onset (first HYK event
      within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6
      postpartum). The effect of ketosis status on blood glucose within 42 DIM was
      evaluated using a generalized linear mixed model. No effect was observed of HYK
      on glucose concentration in primiparous cows. Multiparous cows with early-onset
      HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic
      cows. Overall, primiparous cows had a lower prevalence and incidence of
      hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was
      associated with higher first test-day milk production and 100 DIM milk
      production. In conclusion, hypoglycemia mainly occurred in multiparous cows with
      early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia.

PMID- 28501413
TI  - Managing Traumatic Brain Injury: Translating Military Guidelines to the
      Wilderness.
AB  - Traumatic brain injury (TBI) is a common injury on the battlefield. Much of what
      medics do to manage these injuries on the battlefield can be translated to other
      austere environments, such as wilderness or disaster settings. The recognition
      and diagnosis of TBI can be difficult even in the hospital, but basic
      understanding of how to define a TBI and prevent secondary injuries can be
      accomplished with relatively few resources and little training. This article
      outlines what a TBI is and how to manage it in the field.

PMID- 28501414
TI  - Editorial commentary: Genetic contributions to cardiovascular disease: The
      blurred lines between monogenic and polygenic traits.

PMID- 28501415
TI  - Reduced electrode arrays for the automated detection of rhythmic and periodic
      patterns in the intensive care unit: Frequently tried, frequently failed?
AB  - OBJECTIVE: To investigate the effect of systematic electrode reduction from a
      common 10-20 EEG system on pattern detection sensitivity (SEN). METHODS: Two
      reviewers rated 17130 one-minute segments of 83 prospectively recorded cEEGs
      according to the ACNS standardized critical care EEG terminology (CCET),
      including burst suppression patterns (BS) and unequivocal electrographic
      seizures. Consensus annotations between reviewers were used as a gold standard to
      determine pattern detection SEN and specificity (SPE) of a computational
      algorithm (baseline, 19 electrodes). Electrodes were than reduced one by one in
      four different variations. SENs and SPEs were calculated to determine the most
      beneficial assembly with respect to the number and location of electrodes.
      RESULTS: High automated baseline SENs (84.99-93.39%) and SPEs (90.05-95.6%) were
      achieved for all patterns. Best overall results in detecting BS and CCET patterns
      were found using the "hairline+vertex" montage. While the "forehead+behind ear"
      montage showed an advantage in detecting ictal patterns, reaching a 15% drop of
      SEN with 10 electrodes, all montages could detect BS sufficiently if at least
      nine electrodes were available. CONCLUSION: For the first time an automated
      approach was used to systematically evaluate the effect of electrode reduction on
      pattern detection SEN in cEEG. SIGNIFICANCE: Prediction of the expected detection
      SEN of specific EEG patterns with reduced EEG montages in ICU patients.

PMID- 28501416
TI  - Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized
      for Heart Failure.
AB  - BACKGROUND: Digoxin use has been shown to be associated with a lower risk of 30
      day all-cause hospital readmissions in older patients with heart failure (HF). In
      the current study, we examined this association among long-term care (LTC)
      residents hospitalized for HF. METHODS: Of the 8049 Medicare beneficiaries
      discharged alive after hospitalization for HF from 106 Alabama hospitals, 545
      (7%) were LTC residents, of which 227 (42%) received discharge prescriptions for
      digoxin. Propensity scores for digoxin use, estimated for each of the 545
      patients, were used to assemble a matched cohort of 158 pairs of patients
      receiving and not receiving digoxin who were balanced on 29 baseline
      characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for
      outcomes associated with digoxin among matched patients were estimated using Cox
      regression models. RESULTS: Matched patients (n = 316) had a mean age of 83
      years, 74% were women, and 18% African American. Thirty-day all-cause readmission
      occurred in 21% and 20% of patients receiving and not receiving digoxin,
      respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all
      cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI,
      0.38-2.12), or a combined endpoint of all-cause readmission or all-cause
      mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained
      unchanged at 1 year postdischarge. CONCLUSIONS: The lack of an association
      between digoxin and 30-day all-cause readmission in older nursing home residents
      hospitalized for HF is intriguing and needs to be interpreted with caution given
      the small sample size.

PMID- 28501417
TI  - Prevalence of Frailty Assessed by Fried and Kihon Checklist Indexes in a
      Prospective Cohort Study: Design and Demographics of the Kyoto-Kameoka
      Longitudinal Study.
AB  - OBJECTIVE: The Kyoto-Kameoka Study was launched in 2011-2012 to identify the
      associations among food intake, nutritional status, physical activity, oral
      function, quality of life or social capital, the use of long-term care insurance
      (LTCI) system, and healthy lifespan in community-dwelling older people as a part
      of the World Health Organization Safe Community program. DESIGN: A prospective
      cohort study, reporting baseline demographics (cross-sectional data). SETTING AND
      PARTICIPANTS: We conducted 2 mailed self-administered questionnaire surveys; one
      is a complete population survey with a comprehensive survey of needs in the
      sphere of daily life (NSDL) that included 2 different frailty indexes, the Kihon
      Checklist (KCL) and the Fried phenotype, socioeconomic status, general and
      psychological health, and social relationships; followed by the more detailed
      Health and Nutrition Survey. A slightly modified NSDL survey was conducted again
      in 2013. Survival time, LTCI certification, and medical and long-term care costs
      after the baseline survey will be followed. RESULTS: Of 18,231 NSDL
      questionnaires distributed, 13,294 people responded (response rate: 72.92%; mean
      age 73.7 +/- 6.4 and 75.1 +/- 7.2 years for men and women, respectively; 12,054
      people without and 1240 with LTCI certification). In people without LTCI, the
      proportion of robust, prefrail, and frail were 30.3%, 59.8%, and 9.9% in men and
      25.3%, 64.7%, and 10.0% in women, according to the Fried index. The proportion of
      frail people as defined by KCL >=7 was 30.8% in men and 33.3% in women.
      CONCLUSIONS: The study is the first to document frailty prevalence using both
      Fried and KCL measures with a complete city population survey among older
      Japanese in the community as a part of World Health Organization Safe Community
      program. The study is expected to provide valuable evidence of the effects of
      lifestyle habits on long-term care prevention and healthy life span.

PMID- 28501418
TI  - Comparability and feasibility of wrist- and hip-worn accelerometers in free
      living adolescents.
AB  - OBJECTIVE: To determine the comparability and feasibility of wrist- and hip-worn
      accelerometers among free-living adolescents. DESIGN: 89 adolescents (age=13
      14years old) from eight secondary schools in New South Wales (NSW), Australia
      wore wrist-worn GENEActiv and hip-worn ActiGraph (GT3X+) accelerometers
      simultaneously for seven days and completed an accelerometry behavior
      questionnaire. METHODS: Bivariate correlations between the wrist- and hip-worn
      out-put were used to determine concurrent validity. Paired samples t-test were
      used to compare minutes per day in moderate-to-vigorous physical activity (MVPA).
      Group means and paired sample t-tests were used to analyze participants'
      perceptions of the wrist- and hip-worn monitoring protocols to assist with
      determining the feasibility. RESULTS: Wrist-worn accelerometry compared favorably
      with the hip-worn in average activity (r=0.88, p<0.001) and MVPA (r=0.84 p<0.001,
      mean difference=3.54min/day, SD=12.37). The wrist-worn accelerometer had 50%
      fewer non-valid days (75 days, 12%) than the hip-worn accelerometer (n=152,
      24.4%). Participants reported they liked to wear the device on the wrist
      (p<0.01), and that it was less uncomfortable (p=0.02) and less embarrassing to
      wear on the wrist (p<0.01). Furthermore, that they would be more willing to wear
      the device again on the wrist over the hip (p<0.01). CONCLUSIONS: Our findings
      reveal there is a strong linear relationship between wrist- and hip-worn
      accelerometer out-put among adolescents in free-living conditions. Adolescent
      compliance was significantly higher with wrist placement, with participants
      reporting that it was more comfortable and less embarrassing to wear on the
      wrist.

PMID- 28501419
TI  - Brachytherapy for Conservative Treatment of Invasive Penile Carcinoma: Prognostic
      Factors and Long-Term Analysis of Outcome.
AB  - PURPOSE: To report the largest experience with brachytherapy as a conservative
      approach for the treatment of penile carcinoma. METHODS AND MATERIALS: We
      examined the outcomes of 201 patients treated at our institution over 45 years
      for invasive squamous cell carcinoma of the glans penis by brachytherapy.
      RESULTS: With a median follow-up of 10.7 years, local relapse as first failure
      was reported in 37 patients (18.9%), and 24 of 31 patients (77.4%) with local
      failure only were in complete remission after new treatment. At last follow-up 25
      patients (12.4%) underwent partial surgery and 7 (3.5%) total penectomies for
      relapse. Fifty patients (24.8%) presented urethral stenosis requiring at least 1
      dilatation, and 14 (7%) required limited surgeries for toxicities. At 5 years the
      estimated overall survival rate was 79% (95% confidence interval 73%-85%). The
      estimated original local control rate was 82% (95% confidence interval 76%-88%).
      Presence of inguinal lymph node metastasis and tumor size correlated with a
      poorer overall and disease-free survival in univariate and multivariate analyses.
      In univariate analysis, neutrophilia at diagnosis correlated with a higher
      probability of distant relapse (P=.025), and a dose >=62 Gy correlated with
      better local control in N0 patients (P=.038). The risk of complication correlated
      with the dose, treated volume, and dose rate. CONCLUSION: This large
      institutional experience confirms the high local control achieved with
      brachytherapy for penile carcinoma, with the advantage of organ preservation.
      Most local relapses are efficiently salvaged by second-intent surgery.

PMID- 28501420
TI  - Manipulation of visual information affects control strategy during a visuomotor
      tracking task.
AB  - Proper understanding of motor control requires insight into the extent and manner
      in which task performance and control strategy are influenced by various aspects
      of visual information. We therefore systematically manipulated the visual
      presentation (i.e., scaling factor and optical flow density) of a visuomotor
      tracking task without changing the task itself, and investigated the effect on
      performance, effort, motor control strategy (i.e., anticipatory or corrective
      steering) and underlying neuromechanical parameters (i.e., intrinsic muscle
      stiffness and damping, and proprioceptive and visual feedback). Twenty healthy
      participants controlled the left-right position of a virtual car (by means of
      wrist rotations in a haptic robot) to track a slightly curved virtual road
      (presented on a 60" LED screen), while small torque perturbations were applied to
      the wrist (1.25-20Hz multisine) for quantification of the neuromechanical
      parameters. This visuomotor tracking task was performed in conditions with
      low/medium/high scaling factor and low/high optical flow density. Task
      performance was high in all conditions (tracking accuracy 96.6%-100%); a higher
      scaling factor was associated with slightly better performance. As expected,
      participants did adapt their control strategy and the use of proprioceptive and
      visual feedback in response to changes in the visual presentation. These findings
      indicate that effects of visual representation on motor behavior should be taken
      into consideration in designing, interpreting and comparing experiments on motor
      control in health and disease. In future studies, these insights might be
      exploited to assess the sensory-motor adaptability in various clinical
      conditions.

PMID- 28501421
TI  - "What time is my next meal?" delay-discounting individuals choose smaller
      portions under conditions of uncertainty.
AB  - 'Dietary' delay discounting is typically framed as a trade-off between immediate
      rewards and long-term health concerns. Our contention is that prospective
      thinking also occurs over shorter periods, and is engaged to select portion sizes
      based on the interval between meals (inter-meal interval; IMI). We sought to
      assess the extent to which the length of an IMI influences portion-size
      selection. We predicted that delay discounters would show 'IMI insensitivity'
      (relative lack of concern about hunger or fullness between meals). In particular,
      we were interested in participants' sensitivity to an uncertain IMI. We
      hypothesized that when meal times were uncertain, delay discounters would be less
      responsive and select smaller portion sizes. Participants (N = 90) selected
      portion sizes for lunch. In different trials, they were told to expect dinner at
      5pm, 9pm, and either 5pm or 9pm (uncertain IMI). Individual differences in future
      orientation were measured using a monetary delay-discounting task. Participants
      chose larger portions when the IMI was longer (p < 0.001). When the IMI was
      uncertain, delay-discounting participants chose smaller portions than the average
      portion chosen in the certain IMIs (p < 0.05). Furthermore, monetary discounting
      mediated a relationship between BMI and smaller portion selection in uncertainty
      (p < 0.05). This is the first study to report an association between delay
      discounting and IMI insensitivity. We reason that delay discounters selected
      smaller portions because they were less sensitive to the uncertain IMI, and
      overlooked concerns about potential future hunger. These findings are important
      because they illustrate that differences in discounting are expressed in short
      term portion-size decisions and suggest that IMI insensitivity increases when
      meal timings are uncertain. Further research is needed to confirm whether these
      findings generalise to other populations.

PMID- 28501422
TI  - Desideratum for GUT: A functional semantics for sport.

PMID- 28501423
TI  - Teratoma of the nervous system: A case series.
AB  - Teratoma is a common form of germ cell tumors composed of multiple tissues
      foreign to the site in which arise with a histological representation of all
      three germ cell layers. Intracranial teratomas are very rare. In this study, we
      report three cases of intracranial teratomas with an interesting clinical course,
      neuroradiology, and outcome. In addition, we review the literature and convey
      important messages to the neuroscience community regarding issues related to the
      management of these rare tumors. The present cases are interesting examples of
      intracranial teratoma in terms of location of the tumor and neuroimaging
      findings. Delay in surgical intervention may complicate the course of the disease
      with progressive enlargement of tumors and development of complication including
      hydrocephalus. Using endoscopic surgical techniques may emerge as the preferred
      intervention option as compared to other traditional methods. We recommend the
      establishment of a national and international registry for intracranial tumors.

PMID- 28501424
TI  - RO0504985 is an inhibitor of CMGC kinase proteins and has anti-human
      cytomegalovirus activity.
AB  - Public-private partnerships allow many previously unavailable compounds to be
      screened for antiviral activity. Here a screening method was used to identify an
      oxindole compound, RO0504985, from a Roche kinase inhibitor library that
      inhibited human cytomegalovirus (HCMV) protein production. RO0504985 was
      previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2).
      However, using kinase selectivity assays it was found that RO0504985 was an
      inhibitor of several CMGC group kinase proteins, including CDK2. Using virus
      yield reduction assays it was observed that RO0504985 inhibited replication of
      different HCMV strains at low micromolar concentrations. Western blotting was
      used to investigate how RO0504985 inhibited HCMV replication. Treatment of HCMV
      infected cells with RO0504985 inhibited production of the immediate early viral
      IE2 proteins and the late viral protein pp28. Thus, RO0504985 inhibited HCMV
      replication by preventing production of specific HCMV proteins necessary for
      virus replication.

PMID- 28501425
TI  - The effects of kratom on restraint-stress-induced analgesia and its mechanisms of
      action.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa and its extracts are called
      kratom (dried leaves, extract). They contain several alkaloids with an affinity
      for different opioid receptors. They are used in traditional medicine for the
      treatment of different diseases, as a substitute by opiate addicts, and to
      mitigate opioid withdrawal symptoms. Apart from their medical properties, they
      are used to enhance physical endurance and as a means of overcoming stress.
      PURPOSE: The aim of this study was to determine the mechanisms underlying the
      effects of kratom on restraint-stress-induced analgesia which occurs during or
      following exposure to a stressful or fearful stimulus. METHODS: To gain further
      insights into the action of kratom on stress, we conducted experiments using
      restraint stress as a test system and stress-induced analgesia as a test
      parameter. Using transgenic mu opioid-receptor (MOR) deficient mice, we studied
      the involvement of this receptor type. We used nor-binaltorphimine (BNT), an
      antagonist at kappa opioid receptors (KOR), to study functions of this type of
      receptor. Membrane potential assay was also employed to measure the intrinsic
      activity of kratom in comparison to U50,488, a highly selective kappa agonist.
      RESULTS: Treatment with kratom diminished stress-induced analgesia in wildtype
      and MOR knockout animals. Pretreatment of MOR deficient mice with BNT resulted in
      similar effects. In comparison to U50,488, kratom exhibited negligible intrinsic
      activity at KOR alone. CONCLUSIONS: The results suggest that the use of kratom as
      a pharmacological tool to mitigate withdrawal symptoms is related to its action
      on KOR.

PMID- 28501426
TI  - Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through
      Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is an acute and serious
      diabetic complication characterized by renal hypertrophy and renal fibrosis with
      the expansion of extracellular matrices. Diabetic nephropathy has become a major
      cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound
      prescription which has been widely applied in clinical medicine for the
      prevention and treatment of diabetic nephropathy as well as for acute and chronic
      kidney injuries. However, the mechanism of protective effects of SZGB in DN
      remains unclear. MATERIALS AND METHODS: In this research, we investigated the
      effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and
      apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were
      prepared by performing a right uninephrectomy along with a single intraperitoneal
      injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D,
      SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage
      for 12 weeks. Samples from urine, blood and kidneys were collected for
      biochemical, histological, immunohistochemical and western blot analyses.
      RESULTS: We found that rats treated with SZGB showed reduced 24-h urinary protein
      excretion along with reduced serum total cholesterol (TC) and triglyceride (TG)
      levels. SZGB was also shown to prevent the disruption of catalase activity and
      reduce serum urea, creatinine, and renal malondialdehyde while increasing
      glutathione levels. Moreover, SZGB administration markedly improved the
      expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased
      the expression levels of Vimentin, alpha-SMA and Cleaved caspase-3 in the kidneys
      of diabetic rats. The renoprotective effects of SZGB was believed to be mediated
      by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through
      stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling
      pathway in the diabetic kidneys. CONCLUSIONS: Therefore, it is suggested that
      SZGB can restrain epithelial-mesenchymal transition (EMT) through stimulating the
      Nrf2 pathway, which improves renal interstitial fibrosis in DN.

PMID- 28501427
TI  - Ethnopharmacological approach to the herbal medicines of the "Elements Alpha to
      Delta" in Nikolaos Myrepsos' Dynameron. Part II.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dynameron is a Byzantine medical compendium,
      divided into 24 sections, the "Elements", containing 2667 recipes, most of which
      inherited by previous physicians of the classic ancient Greek and Hellenistic,
      and imperial Roman periods. AIM OF THE STUDY: In continuation to our previous
      study concerning the first and largest chapter of the "Element Alpha" of Nikolaos
      Myrepsos' Dynameron (Valiakos et al., 2015), this paper focuses on the plants
      quoted in the recipes of the eight following chapters entitled "About Salts",
      "About Honeypacks" and "About Spreads", all belonging to the same "Element
      Alpha"; "About Antitussives" and "About Suppositories" belonging to the "Element
      Beta"; "About women's Cathartics" belonging to the "Element Gamma"; "About
      Drossaton" and "About Diachrisma", both belonging to the "Element Delta".
      MATERIALS AND METHODS: Our main primary source material was the codex kept in the
      National Library of France (in Paris) under the number grec. 2243, which is the
      older and larger codex of Dynameron (Valiakos et al., 2015). RESULTS: The present
      study led us to the interpretation of 277 plants under different names, among
      which we recognized 57 medicinal plants listed by the European Medicines Agency,
      one of them with negative monograph (i.e. Chelidonium majus). In addition, there
      are identified taxa related to those quoted by EMA as herbal medicines. The
      plants appearing in the examined Elements belong to various families of which the
      most frequent are: Apiaceae 10.11%; Lamiaceae 7.22%; Asteraceae 6.86%; Rosaceae
      6.5% and Fabaceae 6.14%. CONCLUSIONS: A total of 277 species have been
      catalogued, most of which are referred in our previous publication (Valiakos et
      al., 2015). Among them, 56 plants still play a very important role in medical
      practice, as they are used as traditional herbal medicines (www.ema.eu). This
      evidence is a proof that the use of medicinal plants remains valuable from the
      ancient times until today. The recipes, in contrast to older medical compendia,
      contain precise measurements of ingredients and dosages for every drug, which
      seem to reflect empirical logic.

PMID- 28501428
TI  - Management of ovarian stimulation for IVF: narrative review of evidence provided
      for World Health Organization guidance.
AB  - In this paper, a review of evidence provided to the World Health Organization
      (WHO) guideline development, who prepare global guidance on the management of
      ovarian stimulation for women undergoing IVF, is presented. The purpose of
      ovarian stimulation is to facilitate retrieval of multiple oocytes during a
      single IVF cycle. Availability of multiple oocytes compensates for inefficiencies
      in subsequent stages of the cycle, which include oocyte maturation, IVF, embryo
      culture, embryo transfer, and implantation. Multiple embryos can be transferred
      in most women, and spare embryos can be frozen to allow for future chances of
      pregnancy without the need for repeated ovarian stimulation and oocyte retrieval.
      Our evidence synthesis team addressed 10 clinical questions on management of
      ovarian stimulation for IVF, prepared a narrative review of the evidence and
      drafted recommendations to be considered through WHO guideline development
      processes. Our main outcome measures were live birth, clinical pregnancy, and
      ovarian hyperstimulation syndrome.

PMID- 28501430
TI  - Kinetic properties and affinities for sulfonamide inhibitors of an alpha-carbonic
      anhydrase (CruCA4) involved in coral biomineralization in the Mediterranean red
      coral Corallium rubrum.
AB  - We report the kinetic properties and sulfonamide inhibition profile of an alpha
      carbonic anhydrase (CA, EC 4.2.1.1), named CruCA4, identified in the red coral
      Corallium rubrum. This isoform is involved in the biomineralization process
      leading to the formation of a calcium carbonate skeleton. Experiments performed
      on the recombinant protein show that the enzyme has a "moderate activity" level.
      Our results are discussed compared to values obtained for other CA isoforms
      involved in biomineralization. This is the first study describing the biochemical
      characterization of an octocoral CA.

PMID- 28501429
TI  - Permanent prostate brachytherapy postimplant magnetic resonance imaging dosimetry
      using positive contrast magnetic resonance imaging markers.
AB  - PURPOSE: Permanent prostate brachytherapy dosimetry using computed tomography
      magnetic resonance imaging (CT-MRI) fusion combines the anatomic detail of MRI
      with seed localization on CT but requires multimodality imaging acquisition and
      fusion. The purpose of this study was to compare the utility of MRI only
      postimplant dosimetry to standard CT-MRI fusion-based dosimetry. METHODS AND
      MATERIALS: Twenty-three patients undergoing permanent prostate brachytherapy with
      use of positive contrast MRI markers were included in this study. Dose
      calculation to the whole prostate, apex, mid-gland, and base was performed via
      standard CT-MRI fusion and MRI only dosimetry with prostate delineated on the
      same T2 MRI sequence. The 3-dimensional (3D) distances between seed positions of
      these two methods were also evaluated. Wilcoxon-matched-pair signed-rank test
      compared the D90 and V100 of the prostate and its sectors between methods.
      RESULTS: The day 0 D90 and V100 for the prostate were 98% versus 94% and 88%
      versus 86% for CT-MRI fusion and MRI only dosimetry. There were no differences in
      the D90 or V100 of the whole prostate, mid-gland, or base between dosimetric
      methods (p > 0.19), but prostate apex D90 was high by 13% with MRI dosimetry (p =
      0.034). The average distance between seeds on CT-MRI fusion and MRI alone was 5.5
      mm. After additional automated rigid registration of 3D seed positions, the
      average distance between seeds was 0.3 mm, and the previously observed
      differences in apex dose between methods was eliminated (p > 0.11). CONCLUSIONS:
      Permanent prostate brachytherapy dosimetry based only on MRI using positive
      contrast MRI markers is feasible, accurate, and reduces the uncertainties arising
      from CT-MRI fusion abating the need for postimplant multimodality imaging.

PMID- 28501431
TI  - Lipase-catalyzed kinetic resolution as key step in the synthesis of
      enantiomerically pure sigma ligands with 2-benzopyran structure.
AB  - In order to obtain enantiomerically pure sigma1 receptor ligands with a 2
      benzopyran scaffold an Oxa-Pictet-Spengler reaction with the enantiomerically
      pure 2-phenylethanol derivatives (R)-4 and (S)-4 was envisaged. The kinetic
      resolution of racemic alcohol (+/-)-4 using Amano Lipase PS-C II and isopropenyl
      acetate in tert-butyl methyl ether led to the (R)-configured alcohol (R)-4 in 42%
      yield with an enantiomeric excess of 99.6%. The (S)-configured alcohol (S)-4 was
      obtained by Amano Lipase PS-C II catalyzed hydrolysis of enantiomerically
      enriched acetate (S)-5 (76.9% ee) and provided (S)-4 in 26% yield and 99.7% ee.
      The absolute configuration of alcohol (R)-4 was determined by exciton coupled CD
      spectroscopy of the bis(bromobenzoate) (R)-7. The next important step for the
      synthesis of 2-benzopyrans 2 and 3 was the Oxa-Pictet-Spengler reaction of the
      enantiomerically pure alcohols (R)-4 and (S)-4 with piperidone ketal 8 and
      chloropropionaldehyde acetal 12. The conformationally restricted spirocyclic 2
      benzopyrans 2 revealed higher sigma1 affinity than the more flexible aminoethyl
      derivatives 3. The (R)- and (R,R)-configured enantiomers (R)-2 and (R,R)-3
      represent the eutomers of this class of compounds with eudismic ratios of 4.8
      (2b) and 4.5 (2c). High sigma1/sigma2 selectivity (>49) was found for the most
      potent sigma1 ligands (R)-2b, (R)-2c, (R)-2d, and (S)-2d (Ki(sigma1) 9-15nM).

PMID- 28501432
TI  - Diverse size approach to incorporate and extend highly fluorescent unnatural
      nucleotides into DNA.
AB  - We have prepared a series of size-diverse unnatural nucleotides containing
      fluorescent (dApyrTP, dUpyrTP, dUantTP, dUthiTP) and quencher (dUazoTP) units, as
      well as nucleotides presenting small functional groups (dAethTP, dAoctTP,
      dUethTP, dUiodTP), all based on deoxyadenosine and deoxyuridine, and examined
      their suitability for use in enzymatic incorporation and extension into DNA. We
      observed a size-dependence of the incorporation and extension capability
      (following the order dUiodTP=dUethTP=dUthiTP>dUazoTP>dUpyrTP>dUantTP) during
      primer extension. This result was supported by circular dichroism (CD) spectra,
      which revealed a trend in the different B-form DNA structures depending on the
      size of the unit at the 5-position of the deoxyuridine
      (dUiodTP>dUethTP>dUthiTP>dUpyrTP), obtained from the PCR products. Interestingly,
      dUthiTP could be incorporated and extended into long DNA strands during primer
      extension and even PCR amplification, with CD spectroscopy confirming a stable
      secondary B-form duplex DNA structure. We observed full-length extension products
      even when combining dUthiTP with a template containing 24 continuous dA units
      during the primer extension. Thus, we believe that dUthiTP is a promising
      fluorescent nucleotide for a diverse range of biological applications requiring
      multiple incorporation and extension directly without disruption of B-form DNA
      structures.

PMID- 28501433
TI  - Responsiveness of the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) in
      patients with hallux valgus.
AB  - BACKGROUND: In this study, we investigated the responsiveness of the Self
      Administered Foot Evaluation Questionnaire (SAFE-Q) for patient's assessment
      before and after hallux valgus surgery. METHODS: Patient-reported answers on the
      SAFE-Q and Short Form-36 (SF-36) before and at a mean of 3-4 and 9-12 months
      after hallux valgus surgery were analyzed. Data of 100 patients (92 women, eight
      men) from 36 institutions throughout Japan were used for analysis. RESULTS: In
      all subscales of the SAFE-Q, the trend of increased scores after surgery was
      statistically significant (P < 0.001). Among the patients with available scores
      both before and at 9-12 months after surgery (n = 66), the largest effect sizes
      (ESs) were observed for shoe-related (1.60), pain and pain-related (1.05), and
      general health and well-being (0.84) scales. In the SF-36 (n = 64), the largest
      ES was observed for the bodily pain scale (0.86). Less notable changes were
      observed for the remaining SF-36 domains. CONCLUSION: The SAFE-Q is the first
      patient-reported outcome measure which includes a quality of life assessment of
      shoes. In our cohort, the most remarkable responsiveness was observed for the
      shoe-related subscale. Based on its responsiveness, the SAFE-Q appears to be
      sufficient for evaluation of foot-related quality of life before and after
      surgery.

PMID- 28501434
TI  - Risk stratification for predicting symptomatic skeletal events (SSEs) in breast
      cancer patients with bone metastases.
AB  - BACKGROUND: Symptomatic skeletal events (SSEs) affect many patients with bone
      metastases from breast cancer. However, predictive models of SSEs in patients
      with bone metastases from breast cancer have not been established for clinical
      use. The purpose of this study is to examine risk factors for SSEs in those
      patients and by combining these risk factors patients are classified into several
      groups. With this risk-stratification model, we can identify patients at higher
      risk of SSEs and require close follow-up to maintain ADL. METHODS: Participants
      included 189 female patients with bone metastases from breast cancer and treated
      in our institute between 2009 and 2012. To assess risk factors for the first
      SSEs, clinical data at the time of registration were assessed. To estimate the
      effects of covariates, we used cause-specific hazard modeling. RESULTS:
      Multivariate analysis revealed that a high number of metastasized vertebral
      bodies (>=20) (p < 0.001) and elevated carcinoembryonic antigen (CEA) level (>5
      ng/mL) (p = 0.003) were risk factors for SSEs. Patients were classified into four
      subgroups according to the combination of the number of vertebral metastases and
      CEA level: patients with CEA level > 5 ng/mL and >=20 vertebral metastases;
      patients with CEA level <= 5 ng/mL and >=20 vertebral metastases; patients with
      CEA level > 5 ng/mL and <20 vertebral metastases; and patients with CEA level <=
      5 ng/mL and <20 vertebral metastases. Cumulative incidences of SSEs in these four
      subgroups at 6 months were 35.6%, 15.6%, 9.3%, and 3.7%, respectively.
      CONCLUSIONS: Patients with elevated CEA level (>5 ng/mL) and extensive vertebral
      metastases (>=20) should be closely monitored in routine clinical care, to allow
      prevention of pathological fracture or paraplegia with the intervention of
      orthopedists or radiologists.

PMID- 28501435
TI  - Risk factors for cognitive decline following osteoporotic vertebral fractures: A
      multicenter cohort study.
AB  - BACKGROUND: Osteoporotic vertebral fractures (OVFs) are the most common cause of
      intractable back pain and reduced activities of daily living (ADL), which may
      affect cognitive function. However, no previous studies have reported a change in
      cognitive function after OVFs. The purpose was to reveal cognitive function
      changes after OVFs and investigate the risk factors for cognitive decline.
      METHODS: Consecutive patients with symptomatic OVFs were enrolled in a
      prospective multicenter cohort study. The inclusion criteria were age >65 years,
      diagnosis of acute or subacute OVF, and back pain onset within 2 months prior to
      presentation. Cognitive function was assessed with the mini-mental state
      examination. Medical history, radiological findings, and ADL were investigated as
      risk factors for cognitive decline. RESULTS: We recruited a sample of 339
      patients (58 men and 281 women) who met the inclusion criteria. Patients
      underwent examinations and completed questionnaires at both the time of
      enrollment and at 6-month follow-up. At 6-month follow-up, cognitive decline was
      observed in 26 (7.7%) patients. Medical history, including comorbidities and
      sports activities, did not affect odds ratios (ORs). However, elevated ORs were
      associated with delayed union (OR: 4.67, 95% Confidence interval: 1.22-17.87). In
      addition, significantly increased ORs were associated with reduced ADL at 6-month
      follow-up. CONCLUSIONS: The current results revealed the incidence of cognitive
      decline after the onset of OVF. Delayed union and reduced ADL at 6-month follow
      up were associated with cognitive decline. Patients with cognitive decline
      experienced significantly reduced quality of life. These results highlight the
      importance of preventing cognitive impairment in patients with symptomatic OVF.
      Physical treatment or early surgical treatment may provide appropriate options,
      particularly for patients with suspected delayed union.

PMID- 28501436
TI  - Identification of the bovine HSL gene expression profiles and its association
      with fatty acid composition and fat deposition traits.
AB  - Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of
      hydrolysing a variety of esters and is considered to be a candidate gene
      affecting fat deposition traits. Gene expression profiles of HSL were analysed in
      various adipose tissues of cattle, and the effect of HSL on lipid metabolism
      genes was analysed by a PCR array. Novel polymorphisms were identified within the
      HSL regulatory domain by sequencing, and the relationship between HSL variants
      and fat deposition traits was analysed. HSL mRNA was highly expressed in the
      subcutaneous and visceral fat of cattle. CPT1B/CPT1C and other lipocatabolic
      genes were upregulated, and lipogenesis-related genes (FASN, LPL and ACOT12) were
      downregulated by HSL overexpression in BFFs. Five novel variants in the HSL
      functional domain were significantly associated with fat deposition traits,
      including FCR, LBT, MFW and fatty acid composition. HSL plays a pivotal role in
      the regulation of lipolysis and fatty acid biosynthesis in beef cattle.

PMID- 28501437
TI  - Electronic noses: Powerful tools in meat quality assessment.
AB  - Main factors that are considered by consumers when choosing meat products are
      colour and aroma, of which the latter is a more reliable indicator of quality.
      However, a simple sensory evaluation of hedonistic qualities is often not
      sufficient to determine whether protein is past its shelf life, and consumption
      of spoiled meat can lead to serious health hazards. Some volatile compounds can
      be used as spoilage indicators, and so a device equipped with a sensor sensitive
      to particular odorants would prove useful. Unfortunately, no such single compound
      has yet been identified, as the changes taking place in a sample of meat during
      storage are contingent on numerous factors. On the other hand, a combination of
      volatile compounds may form a unique 'fingerprint' which can be analysed pattern
      recognition algorithms with an electronic nose. It can supplement established
      techniques of meat quality assessment by providing results that correlate well
      with hedonic perception in a short time and at a low cost.

PMID- 28501438
TI  - Investigating drug absorption from the colon: Single-pass vs. Doluisio approaches
      to in-situ rat large-intestinal perfusion.
AB  - Traditionally, the colon is considered a secondary intestinal segment in the drug
      absorption process. However, in many cases the role of colonic drug permeability
      cannot be overlooked. The purpose of this research was to compare colon
      permeability data obtained using two different rat perfusion methods the single
      pass intestinal perfusion (SPIP) approach and the closed-loop (Doluisio)
      perfusion model. A list of 14 structurally diverse model drugs was constructed,
      and their rat colon permeability was studied using the two methods. The two sets
      of results were compared to each other, and were evaluated vs. in-vitro, ex-vivo,
      and in-vivo literature values. The SPIP and the Doluisio results exhibited good
      correlation between them (R2=0.81). The best correlation of both sets was
      obtained with transport studies across Caco-2 monolayers (R2~0.9), as well as the
      sigmoidal fit vs. human fraction of dose absorbed (Fabs) data. On the other hand,
      Ussing chambers data, as well as lipophilicity (Log P) data, resulted in weak
      correlation to the in-situ results. In conclusion, the single-pass intestinal
      perfusion (SPIP) and the Doluisio (closed-loop) perfusion models were found to be
      equally convenient and useful for obtaining validated colon permeability values,
      although more human colonic Fabs data are needed for a better understanding of
      colonic drug permeability and absorption.

PMID- 28501439
TI  - Paclitaxel: What has been done and the challenges remain ahead.
AB  - In recent years, the nanotechnology has offered researchers the opportunity to
      solve the problems caused by the vehicle of the standard and first formulation of
      paclitaxel (Taxol(r)), while maximizing the proven antineoplastic activity of the
      drug against many solid tumors. Hence, different types of nanocarriers have been
      employed to improve the efficacy, safety, physicochemical properties and
      pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the
      unique drug that is marketed in three different nanoplatforms for its parenteral
      delivery: polymeric nanoparticles (Abraxane(r)), liposomes (Lipusu(r)), and
      polymeric micelles (Genexol(r), Nanoxel(r) and Paclical(r)). Indeed, a fourth
      nanocarrier might be available soon, because phase III studies of OpaxioTM, a
      polymeric-conjugated, are near completion. Furthermore, other several
      nanoformulations are currently in various stages of clinical trials. Therefore,
      it is only through the critical analysis of clinical evidence from these studies
      that we can get a more concrete idea of what has been achieved with
      pharmaceutical nanotechnology so far. This review attempts to summarize current
      information available regarding the clinical status and the physicochemical
      characteristic of different nanocarriers for paclitaxel delivery in cancer
      therapy. We present an overview of the preclinical and clinical data of these
      systems including their pharmacokinetics, dose and administration, adverse events
      and clinical efficacy.

PMID- 28501440
TI  - Classification of microcrystalline celluloses via structures of individual
      particles measured by synchrotron radiation X-ray micro-computed tomography.
AB  - Microcrystalline cellulose (MCC) is one of the most important excipients due to
      its outstanding binding and tableting properties. Owing to the absence of high
      resolution characterization techniques at the single particle scale, 3D (three
      dimension) microstructure of MCC and its effects on formulation performance
      remain unexamined. The aim of this work was to establish a methodology for single
      particles of MCC type 102 based on synchrotron radiation X-ray micro computed
      tomography (SR-MUCT), principal component analysis (PCA) and partial least square
      discriminant analysis (PLSDA). Scanning electron microscopy, SR-MUCT, powders
      properties together with tensile strength (TS), disintegration time (DT),
      Kawakita plots and force/displacement profiles of tablets were measured. PCA
      PLSDA was applied to evaluate the structural classification of MCC particles on
      the basis of 2D and 3D SR-MUCT derived images. The studied MCCs were found to
      differ in the TS, DT, Kawakita plot and force/displacement, while box ratio and
      Feret ratio had major influence on the principal components, but the angle of
      repose, bulk and tapped density did not exhibit significantly. These findings
      verified that different samples of MCCs from alternative suppliers have
      morphological diversity when assessed at the individual particle level, which
      could result into variation in powder properties and tableting performance.

PMID- 28501441
TI  - Repeatability of topographic corneal thickness in keratoconus comparing VisanteTM
      OCT and Oculus Pentacam HR(r) topographer.
AB  - PURPOSE: To assess the repeatability and reproducibility of VisanteTM OCT and
      Oculus Pentacam HR(r) in measuring central (CCT) and topographic corneal
      thickness (TCT) along the principle meridians in keratoconus (KC) corneae.
      METHOD: Twenty participants diagnosed with KC were recruited. There were two
      study visits. On the first study visit, two repeated corneal thickness
      measurements were obtained with each instrument. Measurements were repeated at
      least 48hrs later in the same order. TCT were recorded in the 90, 180, 45 and 135
      meridians at 1mm intervals across 8mm chord. RESULTS: Mean CCT for VisanteTM OCT
      was 484.97+/-43.14MUm (range: 484.84-486.09) and Oculus Pentacam HR(r) was
      478.86+/-45.31MUm (range: 477.20-480.53). No significant difference in TCT
      between the two visits (p=0.54) and measurements (p=0.63) for VisanteTM OCT. For
      Oculus Pentacam HR(r), no significant difference was found for each visit
      (p=0.18) but differences existed in the measurements outside of the central
      region (p=0.001). Tukey post-hoc analysis shows the differences (p?0.05) were
      found in the +1 and +4 (supero-temporal) locations in the 135 meridian.
      Significant differences were found comparing the two instruments, (p<0.05). Bland
      Altman plots were used to demonstrate the differences between the two instruments
      and indicate their limits of agreement. CONCLUSION: Both instruments gave
      repeatable measurements as no significant differences were found in most
      locations in all meridians. Comparing the two instruments, they were not
      reproducible in all locations.

PMID- 28501442
TI  - Theoretical fitting characteristics of typical soft contact lens designs.
AB  - PUROSE: To calculate theoretical fitting success rates (SR) for a range of
      typical soft contact lens (SCL) designs using a mathematical model. METHOD: A
      spreadsheet mathematical model was used to calculate fitting SR for various SCL
      designs. Designs were evaluated using ocular topography data from 163 subjects.
      The model calculated SR based on acceptable edge strain (within range 0-6%) and
      horizontal diameter overlap (range 0.2-1.2mm). Where lenses had multiple base
      curves (BCs), eyes unsuccessful with the steeper BC were tested with the flatter
      BC and aggregate SR calculated. Calculations were based on typical, current,
      hydrogel and silicone hydrogel SCLs and allowed for appropriate on-eye shrinkage
      (1.0-2.3%). Theoretical results were compared with those from actual clinical
      trials. RESULTS: Theoretical success rates for one-BC lenses ranged from 60.7%
      (95% CI 7.2%) to 90.2% (95% CI 3.7%). With two-BC designs, most combinations
      showed a SR increase with a second BC (84.0%-90.2%). However, one of the two-BC
      combinations showed only negligible increase with a second BC (72.4%-73.0%). For
      designs with lower SR, the greatest contributor to failure was inadequate lens
      diameter. For a given design, differences in shrinkage (i.e. on-eye bulk
      dehydration) had a significant effect on success rate. In comparison with
      historical clinical data, there was a positive correlation between small lens
      fitting prevalence and discomfort reports (r=+0.95, P=<0.001) with a poor
      correlation between theoretical and actual tight/loose fittings. CONCLUSIONS:
      Mathematical modelling is a useful method for testing SCL design combinations.
      The results suggest that judicious choice of additional fittings can expand the
      range of fitting success.

PMID- 28501443
TI  - Meibomian gland dysfunction and its determinants in Iranian adults: A population
      based study.
AB  - PURPOSE: To estimate the prevalence of Meibomian gland dysfunction (MGD) and
      determine the associated factors in the general population in Iran. METHODS: This
      cross-sectional study is based on the data from the second phase of the Shahroud
      Eye Cohort Study conducted in 2014. Of the 4737 participants of the second phase,
      data was available for 4700 people; their mean age was 55.9+/-6.2 years and 2768
      (58.9%) were women. Diagnosis of MGD was made based on the classification of the
      International Workshop on MGD as judged by the examining ophthalmologist. The
      prevalence of MGD was summarized as percentage and 95% confidence intervals (CI),
      and related factors were studied through simple and multiple logistic
      regressions. RESULTS: The diagnosis of MGD in at least one eye was recorded for
      1235 (26.3%) participants; the prevalence of unilateral and bilateral MGD was
      26.3% (95% CI: 24.5-28.1) and 26.1% (95% CI: 24.3-27.9), respectively. In the
      multiple logistic regression analyses, MGD significantly correlated with
      pinguecula [odds ratio (OR)=1.3, 95% CI: 1.12-1.50], hypertension (OR=1.34, 95%
      CI: 1.11-1.61), high-density lipoprotein (HDL) level (OR=0.0992, 95% CI: 0.986
      0.999), diabetes mellitus (OR=0.83, 95% CI: 0.71-0.97), and years of education
      (OR=0.98, 95% CI: 0.96-0.99). CONCLUSIONS: MGD prevalence in this study was lower
      than the rates reported in other studies on Asian populations. Besides HDL level,
      MGD is associated with another ocular surface disorder, namely pinguecula, as
      well as certain systemic diseases such as hypertension and diabetes mellitus.
      These associations should be taken into consideration when diagnosing MGD.

PMID- 28501444
TI  - Modern scleral lenses: Mini versus large.
AB  - The evolution of scleral lenses has led to new formulations of scleral fitting
      concepts and designs. The diameters of modern scleral lenses have been overhauled
      too and they are smaller comparing to the original ones. Nowadays, prescription
      of mini-sclerals supposedly seems in major extension and it appears indeed the
      necessity of some practitioner to differentiate the smaller mini-scleral lenses
      from larger mini-scleral lenses empathizing that they are the "smaller" ones.
      Therefore, it is maybe, necessary a definition of mini-scleral lenses referring
      to the landing zone width in relation to the horizontal visible iris diameter
      (HVID) and the limbus extension. The choice of the total diameter is crucial for
      a successful fitting and it depends majorly on patient's topographic patterns and
      anatomic factors. However, there are other important criteria for the selection
      of the scleral lens diameter based on oxygen supply, bubbles formation,
      mechanical stress on a toric sclera, ocular surface disease protection, entity of
      the vault over the cornea and distribution of the lens weight on the sclera. The
      advantages of mini-scleral lenses are various nonetheless in some cases large
      lenses are necessary. This paper presents a review of the benefits and
      disadvantages of both mini and large scleral lenses analyzing the conditions in
      which it may be better to prefer one diameter to another. A suggestion may be
      that to start fitting the smallest lens as possible, depending on the dimension
      of HVID and limbus width and consider larger lenses only when issues occur.

PMID- 28501445
TI  - Local and systemic humoral immune response in farmed Atlantic salmon (Salmo salar
      L.) under a natural amoebic gill disease outbreak.
AB  - Amoebic gill disease (AGD), caused by the protozoan parasite Neoparamoeba
      perurans, is one of the most significant infectious diseases for Atlantic salmon
      (Salmo salar L.) mariculture. The present study investigated the humoral immune
      response (both local in gill mucus and systemic in serum) of farmed Atlantic
      salmon naturally infected with N. perurans in commercial sea pens, at two
      different stages of the disease and after freshwater treatment. Parameters
      analysed included activity of immune related enzymes (i.e. lysozyme, peroxidase,
      protease, anti-protease, esterase, alkaline phosphatase), IgM levels, and the
      terminal carbohydrate profile in the gill mucus. Overall, greater variations
      between groups were noted in the immune parameters determined in gill mucus than
      the equivalent in the serum. In gill mucus, IgM levels and peroxidase, lysozyme,
      esterase and protease activities were decreased in fish showing longer exposure
      time to the infection and higher disease severity, then showed a sequential
      increase after treatment. Results obtained highlight the capacity of gills to
      elicit a local response to the infection, indicate an impaired immune response at
      the later stages of the disease, and show partial reestablishment of the host
      immune status after freshwater treatment. In addition to providing data on the
      humoral response to AGD, this study increases knowledge on gill mucosal humoral
      immunity, since some of the parameters were analysed for the first time in gill
      mucus.

PMID- 28501446
TI  - The involvement of cathepsin F gene (CTSF) in turbot (Scophthalmus maximus L.)
      mucosal immunity.
AB  - Cathepsin F (CTSF) is a recently described papain-like cysteine protease and
      unique among cathepsins due to an elongated N-terminal pro-region, which contains
      a cystatin domain. CTSF likely plays a regulatory role in processing the
      invariant chain which is associated with the major histocompatibility complex
      (MHC) class II. In this regard, we identified the CTSF gene of turbot as well as
      its protein structure, phylogenetic relationships, and expression patterns in
      mucosal tissues following Vibrio anguillarum and Streptococcus iniae challenge.
      We also determined the expression patterns of CTSF in mucosal tissues after
      vaccinated with the formalin-inactivated V. vulnificus whole-cell vaccine.
      Briefly, turbot CTSF gene showed the closest relationship with that of
      Paralichthys olivaceus in phylogenetic analysis. And CTSF was ubiquitously
      expressed in all tested tissues with the highest expression level in gill. In
      addition, CTSF gene showed different expression patterns following different
      bacterial challenge. The significant quick regulation of CTSF in mucosal surfaces
      against infection indicated its roles in mucosal immunity. Functional studies
      should further characterize avail utilization of CTSF function to increase the
      disease resistance of turbot in maintaining the integrity of the mucosal barriers
      against infection and to facilitate selection of the disease resistant
      family/strain in turbot.

PMID- 28501447
TI  - Comparison of quantitative measurement of foveal avascular zone and macular
      vessel density in eyes of children with amblyopia and healthy controls: an
      optical coherence tomography angiography study.
AB  - PURPOSE: To quantify vessel density of superficial capillary plexus (SCP), deep
      capillary plexus (DCP), and the foveal avascular zone (FAZ) of children's
      amblyopic eyes and to compare the measurements with those of companion eyes and
      age-matched controls. METHODS: Fifteen patients with strabismic amblyopia, and 15
      age-matched controls were included in this cross-sectional study. SCP, DCP, and
      FAZ were measured via optical coherence tomographic angiography (OCTA). RESULTS:
      Mean subject age was 8.2 +/- 2.3 years in the amblyopia group and 8.6 +/- 2.2
      years in the control group. The mean SCP at 1 mm, 2 mm, and 3 mm zones were (in
      the order amblyopic eye, companion eye, control) 1.399 +/- 0.088, 5.854 +/-
      0.195, 12.866 +/- 0.346; 1.467 +/- 0.084, 5.979 +/- 0.182, 12.965 +/- 0.321; and
      1.559 +/- 0.052, 6.343 +/- 0.190, 13.819 +/- 0.423. SCP was significantly lower
      in amblyopic eyes than in companion eyes and controls (P < 0.05). The mean DCP at
      1 mm, 2 mm, and 3 mm zones were 1.425 +/- 0.069, 6.038 +/- 0.186, 13.522 +/-
      0.336; 1.525 +/- 0.072, 6.427 +/- 0.190, 14.286 +/- 0.322; and 1.685 +/- 0.074,
      6.895 +/- 0.198, 15.355 +/- 0.356. DCP was significantly lower in amblyopic eyes
      than companion eyes and controls (P < 0.05). The mean superficial FAZ were 0.287
      +/- 0.091, 0.262 +/- 0.092, and 0.280 +/- 0.097. The mean deep FAZ were 0.382 +/-
      0.092, 0.335 +/- 0.080, and 0.329 +/- 0.085. There was no significant difference
      in FAZ among groups (P > 0.05). CONCLUSIONS: Vessel density of SCP and DCP of
      eyes with amblyopia is lower than that of the companion eye and the age-matched
      controls.

PMID- 28501448
TI  - Pseudomonas versuta sp. nov., isolated from Antarctic soil.
AB  - In this study we analysed three bacterial strains coded L10.10T, A4R1.5 and
      A4R1.12, isolated in the course of a study of quorum-quenching bacteria occurring
      in Antarctic soil. The 16S rRNA gene sequence was identical in the three strains
      and showed 99.7% pairwise similarity with respect to the closest related species
      Pseudomonas weihenstephanensis WS4993T. Therefore, the three strains were
      classified within the genus Pseudomonas. Analysis of housekeeping genes (rpoB,
      rpoD and gyrB) sequences showed similarities of 84-95% with respect to the
      closest related species of Pseudomonas, confirming its phylogenetic affiliation.
      The ANI values were less than 86% to the closest related species type strains.
      The respiratory quinone is Q9. The major fatty acids are C16:0, C16:1 omega7c/
      C16:1 omega6c in summed feature 3 and C18:1 omega7c / C18:1 omega6c in summed
      feature 8. The strains are oxidase- and catalase-positive. Growth occurs at 4-30
      degrees C, and at pH 4.0-10. The DNA G+C content is 58.2-58.3mol %. The combined
      genotypic, phenotypic and chemotaxonomic data support the classification of
      strains L10.10T, A4R1.5 and A4R1.12 into a novel species of Pseudomonas, for
      which the name P. versuta sp. nov. is proposed. The type strain is L10.10T (LMG
      29628T, DSM 101070T).

PMID- 28501449
TI  - Initial Steps in Training the Public about Bleeding Control: Surgeon
      Participation and Evaluation.
AB  - BACKGROUND: With increasing active shooter and intentional mass casualty events,
      as well as everyday injuries resulting in severe bleeding, there have been calls
      for the public to learn bleeding control techniques. The aims of this project
      were to offer bleeding control training to surgeons attending the Clinical
      Congress of the American College of Surgeons (ACS), to determine if the trained
      surgeons believe that teaching bleeding control to the public should be a
      priority of the ACS, and to assess the surgeon trainees' perceptions regarding
      the appropriateness of the course for a public audience. STUDY DESIGN: This was
      an educational program with a post-course evaluation to determine if the bleeding
      control course is appropriate for a public audience. RESULTS: Three hundred forty
      one surgeons were trained. All were trained and successfully performed a return
      demonstration. Regarding perceptions of the participating surgeons that teaching
      bleeding control to the public should be a priority of the ACS, 93.79% of the 322
      surgeons responding indicated agreement with this proposition. Regarding whether
      or not the training was at an appropriate level of difficulty for the public,
      93.13% of the 320 respondents to this item agreed that it was appropriate.
      CONCLUSIONS: The surgeons who were trained were very much in favor of making
      training the public a priority of the ACS. With additional training of surgeons
      and other health care professionals as trainers, and the engagement of the
      public, the goal of having a citizenry prepared to stop bleeding can be achieved.

PMID- 28501450
TI  - Exploring prognosis in chronic relapsing visceral leishmaniasis among HIV
      infected patients: Circulating Leishmania DNA.
AB  - BACKGROUND: Visceral leishmaniasis (VL) affecting HIV-infected patients is
      considered a challenging condition because of its high mortality and relapse
      rates. The approach of this condition is still surrounded by many uncertainties,
      especially regarding the criteria to institute and discontinue secondary
      prophylaxis for VL. The aim of this study was to evaluate the Leishmania
      parasitism kinetic assessed by polymerase chain reaction (PCR) as a possible tool
      in the prognostic assessment in a context in which patients are receiving highly
      active antiretroviral therapy and secondary prophylaxis. METHODS: A prospective
      observation of Leishmania-HIV-co infected patients was performed and two groups
      with distinct clinical prognosis unpredicted by their CD4 count at the moment of
      VL diagnosis and not related to their HIV load control were confirmed. RESULTS:
      Relapsing (R) and non-relapsing (NR) patients had similar antiviral therapy use
      rates, CD4 lymphocyte count medians and HIV load levels at VL-diagnosis. At the
      12-month follow-up, R-patients presented a significantly lower CD4 lymphocyte
      count than NR-patients, without difference in HIV load control. The time between
      HIV and VL diagnoses was longer in the R than NR-group. Comparison between Kaplan
      Meier relapse-free survival curves (time to relapse) using a log rank test showed
      that patients presenting circulating Leishmania DNA had a significantly higher
      risk of clinical VL relapse within 4 months after a positive test (p=0.001).
      CONCLUSIONS: These results reinforce that a negative PCR could be a useful tool
      to support prophylaxis interruption among patients with CD4 counts above
      200cells/mm3 and that a positive PCR suggests imminent VL relapse.

PMID- 28501452
TI  - Promoting Same-Day Discharge for Gynecologic Oncology Patients in Minimally
      Invasive Hysterectomy.
AB  - STUDY OBJECTIVE: Despite clear data demonstrating feasibility, safety, and cost
      effectiveness of same-day discharge after minimally invasive hysterectomy, a
      paucity of data suggests ways to increase same-day discharge rates. Our
      objectives were to promote same-day discharge after minimally invasive
      hysterectomy using preoperative patient education videos, provider same-day
      discharge awareness initiatives, and standardization of postoperative management
      and to investigate reasons for overnight admission after surgery (non-same-day
      discharge). DESIGN: A quality improvement project measured rates of same-day
      discharge, patient satisfaction, and readmission during the 5 months before and
      after video implementation. Readmission rates were calculated as a surrogate for
      safety. A retrospective chart review was conducted of patients who underwent
      minimally invasive hysterectomy during the 5 months after video implementation,
      comparing 43 same-day discharges to 26 non-same-day discharge patients who met
      criteria for same-day discharge. Differences between groups were analyzed using 2
      tailed t tests or logistic regression (continuous variables) and Fisher's exact
      test or chi2 test (categorical variables). Next, providers were educated about
      same-day discharge, and initiatives were implemented to standardize postoperative
      care. Same-day discharge rates were then calculated to evaluate these additional
      interventions (Canadian Task Force classification II-2). SETTING: A gynecologic
      oncology division based at an academic institution and performing surgery at 2
      hospitals. PATIENTS: All patients undergoing minimally invasive hysterectomy for
      both benign and malignant disease, using robot-assisted, straight laparoscopic,
      and radical hysterectomy procedures. INTERVENTIONS: Patient education video,
      provider education about same-day discharge, and initiatives to standardize
      postoperative care. MEASUREMENTS AND MAIN RESULTS: Overall, same-day discharge
      rates decreased from 47% to 35% and readmission rates from 1.7% to 0% after video
      implementation. Greater than 87% of both groups were very or somewhat satisfied
      with their care (p = .71). Excluding patients who did not qualify for same-day
      discharge, the prevideo implementation same-day discharge rate was 72% (n = 78)
      and the postvideo implementation same-day discharge rate was 62% (n = 69). Higher
      patient complexity (p = .003), later case end time (p = .001), longer operative
      time (p = .001), and robot-assisted cases (p = .002) significantly predicted non
      same-day discharge. After implementing initiatives to increase provider same-day
      discharge awareness and to standardize postoperative management, in addition to
      video implementation, the same-day discharge rate increased to 86% (n = 51).
      CONCLUSION: Same-day discharge in a select population is safe and feasible, with
      at least similar patient satisfaction as non-same-day discharge patients. Shorter
      operative time, earlier case end time, lower patient complexity, and non-robot
      assisted approach increase the likelihood of same-day discharge. Patient
      education videos alone did not increase same-day discharges but maintained
      acceptable readmission rates. Communication with providers regarding the same-day
      discharge initiative and standardization of postoperative management with
      preoperative video implementation may lead to increased same-day discharge rates.

PMID- 28501453
TI  - Is fine-needle aspiration a reliable tool in the diagnosis of malignant salivary
      gland tumors?
AB  - PURPOSE: The purpose of the present study was to establish the reliability of
      fine needle aspiration (FNA) in the diagnosis of malignant salivary gland tumors
      in our population and to compare our results with those of other authors.
      MATERIAL AND METHODS: This was a retrospective study of clinical data from 172
      patients, 153 parotid tumors and 19 submandibular tumors who underwent
      preoperative FNA between January 2004 and December 2013. Sensitivity,
      specificity, positive and negative predictive values of FNA for the preoperative
      diagnosis of malignancy were analyzed. RESULTS: For the diagnosis of malignancy
      an S value of 60% was obtained, which means that 40% of malignant tumors were not
      diagnosed by FNA. Besides an E value of 97.5% was obtained, thus indicating that
      FNA was negative for malignancy in up to 97.5% of all benign neoplasms. According
      to predictive values, we observe that FNA hit in 83.3% cases given as malignant
      and in 92% of cases giving as benign (PPV=83,3%; NPV=92%). CONCLUSION: With a
      scarce 60% sensitivity value in our series, fine needle aspiration has evident
      limitations for diagnosis of malignancy in major salivary gland neoplasms. Being
      highly conditioned by the staff and the conditions in which it is performed, FNA
      is a complementary test that helps the preoperative diagnosis of the major
      salivary glands with radiological tests, medical history and physical
      examination, but that alone it is not defining of malignancy.

PMID- 28501454
TI  - Masseteric nerve for gracilis muscle re-innervation in unilateral facial palsy:
      Impact on quality of life.
AB  - BACKGROUND: Unilateral established or congenital facial palsies are usually
      treated with neuromuscular transplantation to reanimate the impaired side of the
      face. One of the most debated points is the motor nerve to choose for the
      reinnervation of the transplant. Contra-lateral healthy facial nerve is usually
      preferred, but in selected cases motor nerve to masseter is considered a valuable
      option. However only a few clinical studies focused on quality of life in this
      subset of patients are available in literature. METHODS: Twenty patients treated
      for established or congenital unilateral facial palsy reanimated with gracilis
      muscle transplant reinnervated with masseteric nerve were retrospectively
      analyzed. The FDI questionnaire on quality of life was administered before and
      after surgery and statistical analysis of results was conducted to score changes.
      RESULTS: Overall results of the questionnaire resulted in a statistically
      significant improvement after surgery, with a p value of 0.05. CONCLUSION: Facial
      animation with gracilis muscle transplant re-innervated with masseteric nerve is
      a safe and reliable procedure in selected unilateral facial palsy patients.
      Results reported here confirm that surgery mainly improves the functional aspects
      of a patient's daily life quality, while the impact on social interactions and
      self-perception is less significant. The comparison of these results with those
      obtained in patients treated with gracilis muscle transplant re-innervated via
      contralateral facial nerve suggests that spontaneity is probably highly relevant
      to improve social aspects of QOL in this subset of patients.

PMID- 28501451
TI  - Habitual exercise levels are associated with cerebral amyloid load in
      presymptomatic autosomal dominant Alzheimer's disease.
AB  - INTRODUCTION: The objective of this study was to evaluate the relationship
      between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in
      a cohort of autosomal dominant AD mutation carriers. METHODS: In 139
      presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network,
      the relationship between self-reported exercise levels and brain amyloid load,
      cerebrospinal fluid (CSF) Abeta42, and CSF tau levels was evaluated using linear
      regression. RESULTS: No differences in brain amyloid load, CSF Abeta42, or CSF
      tau were observed between low and high exercise groups. Nevertheless, when
      examining only those already accumulating AD pathology (i.e., amyloid positive),
      low exercisers had higher mean levels of brain amyloid than high exercisers.
      Furthermore, the interaction between exercise and estimated years from expected
      symptom onset was a significant predictor of brain amyloid levels. DISCUSSION:
      Our findings indicate a relationship exists between self-reported exercise levels
      and brain amyloid in autosomal dominant AD mutation carriers.

PMID- 28501455
TI  - Exploring the acceptability of the available pneumococcal conjugate vaccines in
      Canadian health care professionals and immunization experts.
AB  - BACKGROUND: In children, the 13 and 10-valent pneumoccocal conjugate vaccines
      (PCV13/10) are currently approved for the prevention of invasive pneumococcal
      disease (IPD). Acceptability is a key consideration in the implementation of a
      vaccine program and it is recognized that health professional's attitudes and
      opinions towards vaccines are independent predictors of the success of an
      immunization program. We aimed to survey the beliefs and attitudes for the two
      available PCVs in health care professionals and immunization experts. FINDINGS:
      We interviewed 21 members of Canadian immunization committees and/or participants
      working in frontline healthcare delivery. Overall, participants predominantly
      preferred PCV-13 over PCV10. For most, AOM should not be taken into
      considerations in decisions for pneumococcal vaccination programs implementation.
      AOM was considered an important endpoint of the program but an ineffective
      measure of program success due to the lack of surveillance for the condition.
      Recent evidence pertaining to PCV10 cross-protection against 19A did not affect
      preference but had an impact on perceptions regarding pricing. CONCLUSION: To
      consider implementing any changes to the current program, most participants would
      require more evidence regarding PCV10 cross-protection and effectiveness against
      OM. Decreasing vaccine price was cited as a positive outcome of funding both
      vaccines.

PMID- 28501457
TI  - Pushing Bacterial Biohybrids to In Vivo Applications.
AB  - Bacterial biohybrids use the energy of bacteria to manipulate synthetic materials
      with the goal of solving biomedical problems at the micro- and nanoscale. We
      explore current in vitro studies of bacterial biohybrids, the first attempts at
      in vivo biohybrid research, and problems to be addressed for the future.

PMID- 28501456
TI  - Assessing age-dependent susceptibility to measles in Japan.
AB  - BACKGROUND: Routine vaccination against measles in Japan started in 1978. Whereas
      measles elimination was verified in 2015, multiple chains of measles transmission
      were observed in 2016. We aimed to reconstruct the age-dependent susceptibility
      to measles in Japan so that future vaccination strategies can be elucidated.
      METHODS: An epidemiological model was used to quantify the age-dependent immune
      fraction using datasets of vaccination coverage and seroepidemiological survey.
      The second dose was interpreted in two different scenarios, i.e., booster and
      random shots. The effective reproduction number, the average number of secondary
      cases generated by a single infected individual, and the age at infection were
      explored using the age-dependent transmission model and the next generation
      matrix. RESULTS: While the herd immunity threshold of measles likely ranges from
      90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the
      estimated immune fraction in Japan was below those thresholds in 2016, despite
      the fact that the estimates were above 80% for all ages. If the second dose
      completely acted as the booster shot, a proportion immune above 90% was achieved
      only among those aged 5years or below in 2016. Alternatively, if the second dose
      was randomly distributed regardless of primary vaccination status, a proportion
      immune over 90% was achieved among those aged below 25years. The effective
      reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to
      3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination
      schedule were continued, the reproduction number is projected to range from 1.50
      to 3.01 and 1.39 to 2.78, respectively, in 2025. CONCLUSION: Japan continues to
      be prone to imported cases of measles. Supplementary vaccination among adults
      aged 20-49years would be effective if the chains of transmission continue to be
      observed in that age group.

PMID- 28501458
TI  - In Vivo Molecular Bioluminescence Imaging: New Tools and Applications.
AB  - in vivo bioluminescence imaging (BLi) is an optical molecular imaging technique
      used to visualize molecular and cellular processes in health and diseases and to
      follow the fate of cells with high sensitivity using luciferase-based gene
      reporters. The high sensitivity of this technique arises from efficient photon
      production, followed by the reaction between luciferase enzymes and luciferin
      substrates. Novel discoveries and developments of luciferase reporters,
      substrates, and gene-editing techniques, and emerging fields of applications,
      promise a new era of deeper and more sensitive molecular imaging.

PMID- 28501459
TI  - [Cancer, radiotherapy and immune system].
AB  - Novel paradigms emerge in oncology today. Systemic treatments are more effective
      and diversified along with an increased life expectancy in oligometastatic
      patients. Stereotactic radiotherapy using hypofractionation opens new
      perspectives for local tumour control. The area of radiobiology has expanded with
      integration of tumour microenvironment in which radiation-induced inflammation
      mediators and immune system play a major role. Immunity checkpoints inhibitors
      experience a major development. This rapidly evolving field seems involved in the
      abscopal effects, especially when radiation is combined with checkpoints
      inhibitors, as demonstrated in numerous preclinical studies and several clinical
      trials. Paradoxically, irradiation also produces immunosuppressive effects. This
      manuscript aims to report the dual effects of ionizing radiation on the immune
      system and reviews some results of the combination of radiation and immunity
      chekpoints inhibitors and also research perspectives.

PMID- 28501460
TI  - Involvement of JNK signaling in IL4-induced M2 macrophage polarization.
AB  - It has been generally accepted that alternatively activated macrophages (M2),
      which can be induced by type 2 cytokines such as IL-4, is responsible for tissue
      repair. However, the function of JNK in IL-4-induced M2 macrophage polarization
      remains unclear. Here, we demonstrated that M0 macrophages can be polarized into
      M2 status in response to IL-4 stimulation with the increased expression of the M2
      specific molecular markers. We also found that IL-4 induced higher expression of
      JNK and transcription factor c-Myc in M2 macrophages. Our Q-PCR and Western blot
      results showed that JNK increased the expression of c-Myc and M2 markers Arg1,
      Mrc1. We also demonstrated c-Myc was the downstream of IL-4-JNK pathway. Further,
      the depletion of c-Myc, Arg1 and Mrc1 could inhibit the migration ability of M2
      macrophages. Taken together, our data establishes a new role for JNK signaling in
      IL-4-induced alternative activation of macrophages and may provide a novel
      strategy for immune therapy.

PMID- 28501461
TI  - Spliceosome-associated factor CTNNBL1 promotes proliferation and invasion in
      ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecologic malignancy and the molecular
      pathogenesis of high-grade serous ovarian carcinoma has not been completely
      characterized. Numerous studies have shown that altered splicing patterns and
      splicing factors were found to contribute to tumor development and progression.
      In this study, we demonstrated that spliceosome-associated factor CTNNBL1 was
      significantly upregulated in high-grade serous ovarian carcinoma, the elevated
      level of CTNNBL1 indicates poor prognosis in patients with high-grade serous
      ovarian carcinoma. Functional characterization revealed that CTNNBL1 promoted the
      proliferation and invasion of ovarian cancer cells in vitro. Furthermore, through
      transcriptome analysis, we found CTNNBL1 regulates multiple splicing events and
      gene expression in ovarian cancer cells. Importantly, we identified IFI16 and
      FOXM1 splicing was regulated by CTNNBL1. To our knowledge, this is the first
      study exploring the expression, functional roles and regulated splicing events of
      CTNNBL1 in ovarian cancer.

PMID- 28501462
TI  - Ray resection in paediatric population.
AB  - AIM: Evaluation of clinical and functional outcome of ray resection in paediatric
      population and description of key aspects of surgical technique. MATERIAL AND
      METHODS: We performed a retrospective review of all patients undergoing surgery
      between 2010-2015. INCLUSION CRITERIA: one or more ray resections of the hand and
      a minimum of one year follow-up. Evaluation of clinical characteristics,
      functional and cosmetic results, complications, need for psychological support
      and patient or family satisfaction. RESULTS: Four patients met the inclusion
      criteria. The mean age at surgery was 5 years (range, 1-14 years). Aetiology was:
      fibrolipomatous hamartoma, traumatic amputation, radial deficiency and complex
      syndactyly. Second ray was resected in three patients and third and fourth ray in
      one. No finger transfer was performed. No immediate post-operative complications
      were found at the final evaluation. None of them needed psychological support.
      All the patients showed excellent clinical and functional results with a high
      grade of satisfaction. DISCUSSION: Ray resection of the hand has been used as
      salvage procedure in patients with vascular lesions, tumours, trauma, infections
      or congenital malformations. There are only a few published studies including
      small samples in adults or case reports, with no references in the paediatric
      population. CONCLUSION: Ray resection of the hand is a useful and safe technique
      in paediatric population, obtaining excellent cosmetic and functional results in
      those cases in which it is impossible to preserve one or more fingers.

PMID- 28501463
TI  - Home-based rehabilitation in the postoperative treatment of flexor tendon repair.
AB  - OBJECTIVE: To evaluate the results and complications of flexor tendon repair in
      which a home-based rehabilitation program was utilized without the assistance of
      a hand therapist during the first 4postoperative weeks. MATERIAL Y METHODS:
      Between July 2009 and July 2014, a total of 21 digits in 15 patients were treated
      in our institution for complete laceration of the flexor tendons within the
      flexor pulley system (zone 1 and 2). Passive and active exercises performed by
      the patients themselves were started the morning after the operation. Data, as
      range-of-motion and complications, were collected 6months after the surgery.
      RESULTS: Fifteen digits had full recovery of flexion. One patient suffered a
      rupture in the fifth postoperative week. Ten of the 21 digits developed a flexion
      contracture of the proximal interphalangeal joint; in 5 the contracture was less
      or equal to 10 degrees  without impairment of function or aesthetics. DISCUSSION:
      Over recent decades, specialized hand therapy has been of great importance in the
      postoperative treatment of hand diseases. Unfortunately, these professionals are
      not always available in our area in the first days after surgery. With this
      protocol, the patient is in charge of carrying out the postoperative exercises,
      which could lead to a worse final result and a higher rate of complications.
      CONCLUSION: The home-based rehabilitation program yielded complete recovery of
      joint mobility in most cases with a low complication rate.

PMID- 28501464
TI  - The connection between nursing diagnosis and the use of healthcare resources.
AB  - AIM: The health service invests up to 75% of its resources on chronic care where
      the focus should be on caring rather than curing. Nursing staff focuses their
      work on such care. Care requires being redorded in health histories through the
      standardized languages. These records enable useful analyses to organisational
      and healthcare decision-making. Our proposal is to know the association of
      between nursing diagnosis and a higher total expenditure on health. METHOD: An
      observational cross-sectional analytical study was performed based on data from
      electronic health records in Primary Care (Drago-AP), hospital discharges (CMBD
      AH) and prescriptions (REC-SCS) of patients over 50 from 2012-2013 in the Canary
      Islands. A descriptive, bivariate and multivariate analysis was undertaken to
      create a predictive model on the use of resources. INDEPENDENT VARIABLES:
      Sociodemographic (age, sex, type of health-care affiliation, type of prescription
      charge) and nursing diagnosis (ND) recorded in late 2012. Dependent variables:
      Resources consumed in 2013. RESULTS: 582,171 patients met the criteria for
      inclusion. 53.0% of them were women with an average age of 64.3 years (SD
      10.8years). 53.2% were pensioners. 49% of the included population had an ND, with
      an average of 2.1ND per patient. The average costs per patient were 1824.62?
      (with a median of 827.5?) 25 and 27 percentiles of 264.1? and 1824.7?,
      respectively. The bivariate analysis showed a significant correlation between
      these expenses and all the demographic variables; the expenses increased when a
      nursing diagnosis has been made (Spearman's rank=0.37: the more diagnoses, the
      more expenses). In the multivariate analysis, a first linear regression with the
      sociodemographic variables as independent variables explains 13.7% of the
      variability of the logarithm of the full costs (R2=0.137). If we add to this
      model the presence of nursing diagnoses, the explanatory capacity reaches 19.77%
      (R2=0.1977). CONCLUSION: Compared with a model that only consists of
      sociodemographic variables, nursing diagnoses can enhance the explanatory
      capacity of the use of healthcare resources.

PMID- 28501465
TI  - Candiduria: Evidence-based approach to management, are we there yet?
AB  - Candiduria is considered one of the most controversial issues in patient
      management. Neither the diagnosis nor the optimal treatment options are
      standardized. This is further complicated by lack of defined laboratory criteria
      for diagnosis as most of the studies were set for bacterial rather than fungal
      urinary tract infection (UTI). Furthermore, since Candida species is a known
      commensal of the genitourinary tract its presence in the urine sample adds
      ambiguity to making a definitive diagnosis of candidal UTI. Guidelines for
      diagnosis and management of candiduria have changed considerably over the past
      decades. In 1960s, the condition was believed to be benign with no intervention
      required. However, over the years new dimensions were added to address the issues
      associated with candiduria until the latest Infectious Diseases Association of
      America (IDSA) guidelines were published in 2009, which indicated that there was
      an increase in the incidence of candiduria caused by more resistant non-Candida
      albicans species. Further complicating the issue is the observation that
      candiduria may be the only indicator of a more serious invasive candidiasis,
      especially in immunocompromised patients. Long-term urinary catheterization is
      considered to be the most significant risk factor for candiduria followed by
      antibiotic use and diabetes. Strategies for management are based on the
      evaluation of candiduria in the context of the clinical setting to determine its
      relevance and make an appropriate decision about the need for antifungal therapy.
      Fluconazole is the main drug used for its efficacy and least complications. Other
      options include bladder irrigation with amphotericin B, flucytosine or parenteral
      amphotericin B. Since azoles other than fluconazole and all echinocandins are
      poorly excreted in urine they have been found to be less effective in candiduric
      patients.

PMID- 28501466
TI  - A case of bilateral otomycosis associated with Aspergillus flavus and A. terreus
      in Taiwan.
AB  - Otitis externa caused by fungi (otomycosis) occurs more commonly in tropical
      areas with high moisture than in temperate regions. Bilateral otomycosis is,
      however, rarely reported. In a case of bilateral otitis externa in a 56-year-old
      male patient in Taiwan, direct microscopic examination of the cerumen as well as
      isolation of strains indicated the presence of two Aspergillus species being
      different in each of both ears. The species were identified by DNA sequence
      comparisons and additional morphological confirmation of diagnostic
      characteristics as Aspergillus flavus and Aspergillus terreus. The rarely
      reported occurrence of two Aspergillus species in otitis of the same patient
      deserves attention in other cases of otomycosis, particularly with respect to
      potentially different resistances of different species against antifungals.
      Treatment with nystatin/neomycin was not successful, but with clotrimazole was
      effective.

PMID- 28501467
TI  - Keratitis by a rare pathogen Colletotrichum gloeosporioides: A case report.
AB  - Colletotrichum species have been reported infrequently as the cause of keratitis
      or subcutaneous lesions. The patient we describe developed keratitis after ocular
      trauma. The sample from the corneal scrapings grew Colletotrichum gloeosporioides
      as identified from morphological characters and DNA sequence of the 'Internal
      Transcribed Spacer' (ITS) region. The patient underwent topical application of
      amphotericin-B followed by itraconazole and natamycin treatment. Simultaneous
      oral voriconazole regimen leads to complete regression of corneal ulcer. This
      report highlights the fact that early and accurate identification and therapy can
      resolve keratitis caused by rare pathogen C. gloeosporioides.

PMID- 28501468
TI  - [Tinea capitis: Main mycosis child. Epidemiological study on 10years].
AB  - Despite the changes in their epidemiology, and the improving level of hygiene of
      the population, tinea capitis is still considered a public health problem in our
      country, and is the most common type of dermatophytosis in our country. The aim
      of our study was to evaluate the epidemiological, clinical and mycological
      features of tinea capitis in children encountered in the Tunis region. A
      retrospective study concerned 1600 children aged 6 months to 15 years suspected
      to have tinea capitis was conducted in Parasitology-Mycology laboratory, Rabta
      hospital, over a 10-years period (2005-2014). Dermatophyte infections were
      confirmed using scalp scrapings examinated with direct microscopy using potash at
      30% and/or culture on Sabouraud medium agar. Tinea capitis diagnosis was
      confirmed in 947 cases (59.18%). The sex ratio was 2.61 and the average age of
      6.28 years with predominance in the age group of 4 to 8 years (52.27%). The most
      common clinical presentation was ringworm (87.65%). Ringworm large plaque was
      predominant (65.9%). Direct examination was positive in 884 cases (93.35%).
      Microsporic tinea was the most frequent (63.25%) followed by trichophytic tinea
      (29.78%). Positive cultures of dermatophytes were obtained in 912 cases (96.30%).
      The following dermatophyte species were isolated: Microsporum canis (67%),
      Trichophyton violaceum (31.68%), Trichophyton mentagrophytes (0.66%), Microsporum
      audouinii (0.22%), Trichophyton schoenleinii (0.22%) and Microsporum gypseum
      (0.22%). M. canis is currently the most frequently incriminated species in tinea
      capitis in Tunisia. This change is related to a change in behavior of our
      population, in fact the cat; main reservoir of M. canis cohabiting increasingly
      with Tunisian families.

PMID- 28501469
TI  - Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides
      as Delivery Vectors.
AB  - A number of potent drugs for the treatment of brain diseases are available.
      However, in order for them to reach their target site of action, they must pass
      the blood-brain barrier (BBB). The capillary endothelium comprises the major
      barrier of the BBB and allows only passive permeation of some small lipophilic
      molecules. Brain delivery of the larger biopharmaceuticals, which today includes
      an increasing number of novel drug entities, is therefore restricted, both due to
      their molecular size and their hydrophilic nature. Thus, the development of novel
      drug entities intended for the treatment of brain diseases such as
      neurodegenerative diseases or brain cancers require a delivery strategy for
      overcoming the BBB before reaching its final target within the brain. Peptide
      based delivery vector is an emerging tool as shuttles for drug delivery across
      the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated
      transcytosis, and the paracellular route. The latter, however, being
      controversial due to the risk of co-delivery of blood-borne potential harmful
      substances. On the other hand, a number of studies report on drug delivery across
      the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated
      transcytosis, indicating that peptides and peptide vectors may be of use in a
      central nervous system delivery context.

PMID- 28501470
TI  - Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro
      Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma
      Concentration of Unbound Drugs, and Their Profiles for Substrates of
      Transporters.
AB  - Accurate prediction of target occupancy facilitates central nervous system drug
      development. In this review, we discuss the predictability of serotonin
      transporter (SERT) occupancy in human brain estimated from in vitro Ki values for
      human SERT and plasma concentrations of unbound drug (Cu,plasma), as well as the
      impact of drug transporters in the blood-brain barrier. First, the geometric
      means of in vitro Ki values were compared with the means of in vivo Ki values
      (Ki,u,plasma) which were calculated as Cu,plasma values at 50% occupancy of SERT
      obtained from previous clinical positron emission tomography/single photon
      emission computed tomography imaging studies for 6 selective serotonin
      transporter reuptake inhibitors and 3 serotonin norepinephrine reuptake
      inhibitors. The in vitro Ki values for 7 drugs were comparable to their in vivo
      Ki,u,plasma values within 3-fold difference. SERT occupancy was overestimated for
      5 drugs (P-glycoprotein substrates) and underestimated for 2 drugs (presumably
      uptake transporter substrates, although no evidence exists as yet). In
      conclusion, prediction of human SERT occupancy from in vitro Ki values and
      Cu,plasma was successful for drugs that are not transporter substrates and will
      become possible in future even for transporter substrates, once the transporter
      activities will be accurately estimated from in vitro experiments.

PMID- 28501471
TI  - Comparison of endoscopic ultrasound guided fine needle aspiration and PET/CT in
      preoperative diagnosis of pancreatic adenocarcinoma.
AB  - BACKGROUND: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the
      procedure of choice to investigate and sample pancreatic masses for the
      preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of
      18fluoro-deoxyglucose positron emission tomography/computed tomography (PET/CT)
      in PDAC is debated. This study evaluates the role of EUS-FNA as compared to
      PET/CT in the preoperative evaluation of PDAC. METHODS: Preoperative evaluation
      by PET/CT and EUS-FNA was performed on 25 patients with pancreatic solid lesions,
      who underwent a subsequent Whipple procedure or partial pancreatic resection.
      RESULTS: This series included 19 PDACs and 6 non-PDACs including 1 metastatic
      breast ductal adenocarcinoma, 2 low grade neuroendocrine tumors, 2 chronic
      pancreatitis and 1 gastrointestinal tumor abutting the pancreas. EUS-FNA
      correctly diagnosed 18 of 19 PDACs, 1 metastatic breast ductal adenocarcinoma and
      all 5 of the other non-PDAC cases. One case of well differentiated PDAC was
      negative on EUS-FNA. PET/CT provided excellent size and was positive in 14 of 19
      PDACs and the metastatic breast ductal adenocarcinoma. The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      for EUS-FNA in diagnosis of selected pancreatic tumors were 91%, 100%, 100%, 50%
      and 92%, respectively, while they were 65%, 100%, 100%, 20% and 68% for PET/CT,
      respectively. CONCLUSIONS: Compared to PET/CT, EUS-FNA has a higher sensitivity
      and accuracy for preoperative diagnosis of PDAC. However, PET/CT provides
      excellent size, volume and stage information. A combination of both PET/CT and
      EUS will better help guide diagnosis and treatment of pancreatic adenocarcinoma.

PMID- 28501473
TI  - Electrical status epilepticus during sleep in Mowat-Wilson syndrome.
AB  - AIM: Mowat-Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present
      in 70-75% of Patients and an age-dependent electroclinical pattern has been
      described. Up to date, there are studies with overnight sleep EEGs, probably
      because of the severe intellectual disability (ID) and hyperactivity of these
      Patients. Our purpose was to verify the hypothesis that MWS Patients might have
      electrical status epilepticus in slow wave sleep (ESES pattern). METHODS: A
      retrospective analysis of anamnestic and electrographic data was performed on 7
      consecutive MWS Patients followed between 2007 and 2016. Only Patients with at
      least one overnight sleep EEG were included in the study. RESULTS: Five out of 7
      Patients had overnight sleep EEG studies and were included in this study. All of
      them had an anterior ESES pattern with spike-and-wave index>85%. The architecture
      of sleep was abnormal. An ESES related regression of cognitive and motor
      functions with impact on daily activities (ESES-related syndrome) was
      demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of
      cognitive and motor performances was observed when the epileptiform activity
      during sleep was successfully controlled or it was spontaneously reduced.
      CONCLUSIONS: The clinical significance of the ESES pattern is hard to assess in
      MWS Patients due to severe ID, but changing in behaviour or in motor and
      cognitive functions should mandate sleep EEG investigation and, if ESES is
      present, an appropriate treatment should be tried. Furthermore, overnight sleep
      EEG recordings, if regularly performed in the follow up, might help to understand
      if ESES pattern hampers the cognitive and communicative profile in MWS.

PMID- 28501472
TI  - Prokaryotic expression of a codon-optimized capsid gene from duck circovirus and
      its application to an indirect ELISA.
AB  - Duck circovirus (DuCV), as a causative agent of long-term immunosuppressive
      disease, has caused heavy damage to waterfowl breeding worldwide. In this study,
      the full-length Cap (capsid) gene of DuCV was expressed in Escherichia coli (E.
      coli) for the first time by optimizing the codons in its nuclear localization
      signal (NLS) regions. The recombinant protein was expressed as inclusion bodies,
      and the quantification of purified Cap protein could reach 0.29mgmL-1. Moreover,
      an indirect ELISA method (Cap-ELISA) was established based on the recombinant Cap
      protein. The results of the optimization for Cap-ELISA revealed that the optimum
      concentration of the coating antigen and serum dilution ratio were 19.5ng per
      well and 1:1280, respectively. The cut-off value of the Cap-ELISA for positive
      sample detection was 0.145, the sensitivity of that reached 1:25600, and it was
      specific for the detection of DuCV anti-sera. In comparative experiments using 56
      clinically suspected DuCV-infection samples, the Cap-ELISA showed a 94.64%
      coincidence rate with the PCR test. These results indicated that codon
      optimization is a reasonable strategy to obtain an intact Cap protein, and this
      Cap-ELISA is suitable for extensive applications in DuCV serological diagnosis.

PMID- 28501474
TI  - A case of mumps-related acute encephalopathy with biphasic seizures and late
      reduced diffusion.
AB  - BACKGROUND: Mumps is a common childhood viral disease characterized by fever and
      swelling of the parotid gland. The prognosis is generally good, although some
      complications, such as encephalitis (0.1%), exist. Acute encephalopathy with
      biphasic seizures and late reduced diffusion is the most common type of acute
      encephalopathy. However, this type of encephalopathy has not been reported in
      association with mumps infection. PATIENT: A previously healthy 3-year-old
      Japanese boy had a brief convulsion after fever for 3days, and then had conscious
      disturbance and parotitis. After several days, he had a second brief convulsion
      and was admitted. Increased serum amylase levels and presence of anti-mumps
      immunoglobulin M antibody confirmed mumps parotitis. The patient had another
      brief seizure later the day of admission. He did not have status or cluster
      seizures, although the biphasic nature of his seizures, conscious disturbance
      between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic
      resonance images were consistent with acute encephalopathy with biphasic seizures
      and late reduced diffusion. DISCUSSION: In Japan, the mumps vaccine is not
      administered as a part of routine immunizations. It thus has low coverage (30
      40%), and as a result, mumps infections are still common. However, this is the
      first case of mumps-related acute encephalopathy with biphasic seizures and late
      reduced diffusion. This case may be representative of only a minority of patients
      with mumps-associated central nervous system involvement. Nevertheless, this
      diagnostic possibility may be considered. In order to prevent mumps-related
      complications, routine mumps vaccination might be warranted.

PMID- 28501475
TI  - Long term kinetic measurements revealing precision and general performance of
      surface plasmon resonance biosensors.
AB  - This work presents an extensive parameter list that facilitates a survey of
      biosensor performance using Biacore instruments for kinetic binding studies. Six
      long term measurements were performed using a strongly interacting antigen
      antibody (beta2 microglobulin) system. Both Single Cycle Kinetic (SCK) and Multi
      Cycle Kinetic (MCK) were executed each with five different analyte
      concentrations. The overall comparison of the long term monitored parameters,
      like the dissociation constant (KD with approximately 3-6% relative percental
      standard deviation), the association and dissociation rate constants (ka, kd),
      the analyte binding capacity (Rmax), chi2 and the sum of the absolute values of
      the residuals, revealed the delicate factors that make the system performance
      vulnerable. The main influential factors on kinetic performance were the
      regeneration conditions, the quality of the sensor surface, the usage time and
      alteration of the sensor surface, the dilution series and the number of run
      cycles (about 250-600 per chip). Moreover the direct comparison of MCK and SCK
      uncovered distinct differences in the accuracy of the KD values. The study of
      sensor chips from two manufacturers showed distinct differences in the precision
      of the data. Using control charts for the surveillance of these parameters
      contributes to an overall better system performance.

PMID- 28501477
TI  - Co-accumulation of cis-regulatory and coding mutations during the
      pseudogenization of the Xenopus laevis homoeologs six6.L and six6.S.
AB  - Common models for the evolution of duplicated genes after genome duplication are
      subfunctionalization, neofunctionalization, and pseudogenization. Although the
      crucial roles of cis-regulatory mutations in subfunctionalization are well
      documented, their involvement in pseudogenization and/or neofunctionalization
      remains unclear. We addressed this issue by investigating the evolution of
      duplicated homeobox genes, six6.L and six6.S, in the allotetraploid frog Xenopus
      laevis. Based on a comparative expression analysis, we observed similar eye
      specific expression patterns for the two loci and their single ortholog in the
      ancestral-type diploid species Xenopus tropicalis. However, we detected lower
      levels of six6.S expression than six6.L expression. The six6.S enhancer sequence
      was more highly diverged from the orthologous enhancer of X. tropicalis than the
      six6.L enhancer, and showed weaker activity in a transgenic reporter assay. Based
      on a phylogenetic analysis of the protein sequences, we observed greater
      divergence between X. tropicalis Six6 and Six6.S than between X. tropicalis Six6
      and Six6.L, and the observed mutations were reminiscent of a microphthalmia
      mutation in human SIX6. Misexpression experiments showed that six6.S has weaker
      eye-enlarging activity than six6.L, and targeted disruption of six6.L reduced the
      eye size more significantly than that of six6.S. These results suggest that
      enhancer attenuation stimulates the accumulation of hypomorphic coding mutations,
      or vice versa, in one duplicated gene copy and facilitates pseudogenization. We
      also underscore the value of the allotetraploid genome of X. laevis as a resource
      for studying latent pathogenic mutations.

PMID- 28501476
TI  - Endothelial cells are not required for specification of respiratory progenitors.
AB  - Crosstalk between mesenchymal and epithelial cells influences organogenesis in
      multiple tissues, such as lung, pancreas, liver, and the nervous system. Lung
      mesenchyme comprises multiple cell types, however, and precise identification of
      the mesenchymal cell type(s) that drives early events in lung development remains
      unknown. Endothelial cells have been shown to be required for some aspects of
      lung epithelial patterning, lung stem cell differentiation, and regeneration
      after injury. Furthermore, endothelial cells are involved in early liver and
      pancreas development. From these observations we hypothesized that endothelial
      cells might also be required for early specification of the respiratory field and
      subsequent lung bud initiation. We first blocked VEGF signaling in E8.5 cultured
      foreguts with small molecule VEGFR inhibitors and found that lung specification
      and bud formation were unaltered. However, when we examined E9.5 mouse embryos
      carrying a mutation in the VEGFR Flk-1, which do not develop endothelial cells,
      we found that respiratory progenitor specification was impeded. Because the E9.5
      embryos were substantially smaller than control littermates, suggesting the
      possibility of developmental delay, we isolated and cultured foreguts from mutant
      and control embryos on E8.5, when no size differences were apparent. We found
      that both specification of the respiratory field and lung bud formation occurred
      in mutant and control explants. These observations were unaffected by the
      presence or absence of serum. We also observed that hepatic specification and
      initiation occurred in the absence of endothelial cells, and that expansion of
      the liver epithelium in culture did not differ between mutant and control
      explants. Consistent with previously published results, we also found that
      pancreatic buds were not maintained in cultured foreguts when endothelial cells
      were absent. Our observations support the conclusion that endothelial cells are
      not required for early specification of lung progenitors and bud initiation, and
      that the diminished lung specification seen in E9.5 Flk-/- embryos is likely due
      to developmental delay resulting from the insufficient delivery of oxygen,
      nutrients, and other factors in the absence of a vasculature.

PMID- 28501479
TI  - Risk factors for complex regional pain syndrome in patients with surgically
      treated traumatic injuries attending hand therapy.
AB  - STUDY DESIGN: Prospective cohort study. INTRODUCTION: Identification of risk
      factors for CRPS development in patients with surgically treated traumatic
      injuries attending hand therapy allows to watch at-risk patients more closely for
      early diagnosis and to take precautionary measures as required. PURPOSE OF THE
      STUDY: The aim of this study was to evaluate the risk factors for the development
      of complex regional pain syndrome (CRPS) after surgical treatment of traumatic
      hand injuries. METHODS: In this prospective cohort, 291 patients with traumatic
      hand injuries were evaluated 3 days after surgery and monitored for 3 months for
      the development of CRPS. The factors assessed for the development of CRPS were
      age, sex, manual work, postoperative pain within 3 days measured on a Pain
      Numerical Rating Scale (0-10), and injury type (crush injury, blunt trauma, and
      cut laceration injury). RESULTS: CRPS was diagnosed in 68 patients (26.2 %) with
      a duration of 40.10 +/- 17.01 days between the surgery and CRPS diagnosis. The
      mean postoperative pain score was greater in patients with CRPS than in those
      without CRPS (P < .001). Patients with pain scores >= 5 had a high risk of
      developing CRPS compared with patients with pain scores <5 (odds ratio: 3.61,
      confidence interval = 1.94-6.70). Patients with crush injuries were more likely
      to develop CRPS (odds ratio: 4.74, confidence interval = 2.29-9.80). CONCLUSIONS:
      The patients with a pain score of >=5 in the first 3 days after surgery and the
      patients with crush injury were at high risk for CRPS development after surgical
      treatment of traumatic hand injuries. LEVEL OF EVIDENCE: II b.

PMID- 28501478
TI  - Osr1 functions downstream of Hedgehog pathway to regulate foregut development.
AB  - During early fetal development, paracrine Hedgehog (HH) ligands secreted from the
      foregut epithelium activate Gli transcription factors in the surrounding
      mesenchyme to coordinate formation of the respiratory system, digestive track and
      the cardiovascular network. Although disruptions to this process can lead to
      devastating congenital defects, the underlying mechanisms and downstream targets,
      are poorly understood. We show that the zinc finger transcription factor Osr1 is
      a novel HH target as Osr1 expression in the foregut mesenchyme depends on HH
      signaling and the effector of HH pathway Gli3 binds to a conserved genomic loci
      near Osr1 promoter region. Molecular analysis of mouse germline Osr1 mutants
      reveals multiple functions of Osr1 during foregut development. Osr1 mutants
      exhibit fewer lung progenitors in the ventral foregut. Osr is then required for
      the proper branching of the primary lung buds, with mutants exhibiting miss
      located lung lobes. Finally, Osr1 is essential for proper mesenchymal
      differentiation including pulmonary arteries, esophageal and tracheal smooth
      muscle as well as tracheal cartilage rings. Tissue specific conditional knockouts
      in combination with lineage tracing indicate that Osr1 is required cell
      autonomously in the foregut mesenchyme. We conclude that Osr1 is a novel
      downstream target of HH pathway, required for lung specification, branching
      morphogenesis and foregut mesenchymal differentiation.

PMID- 28501480
TI  - Assessing manual dexterity: Comparing the WorkAbility Rate of Manipulation Test
      with the Minnesota Manual Dexterity Test.
AB  - STUDY DESIGN: Cross-sectional study. INTRODUCTION: The WorkAbility Rate of
      Manipulation Test (WRMT), an adaptation of the Minnesota Manual Dexterity Test
      (MMDT), contains a revised board and protocols to improve its utility for therapy
      or fitness assessment. PURPOSE OF THE STUDY: To describe the development and
      preliminary psychometric properties of WRMT. METHODS: Sixty-six healthy
      participants completed MMDT and WRMT in a random order followed by a user
      experience survey. We compared tests using repeated-measures analysis of
      variance, test-retest reliability, and examined agreement between tests. RESULTS:
      Despite the similarities of these 2 instruments, the different administration
      protocols resulted in statistically different score distributions (P < .001).
      Results supported good test-retest reliability of WRMT (placing test ICC = 0.88
      0.90 and turning test ICC = 0.68-0.82). The WRMT correlated moderately with MMDT
      (r = 0.81 in placing test and r = 0.44-0.57 in turning test). Bland-Altman plot
      showed that the differences in completion time were 3.8 seconds between placing
      tests and 19.6 (both hands), 0.3 (right hand), and 3.9 (left hand) seconds
      between turning tests. Overall, participants felt that the instruction of WRMT
      was easier to follow (44%) and preferred its setup, color, and depth of the test
      board (49%). Time required to complete 1 panel of 20 disks correlated highly with
      the time needed to finish a complete trial of 60 disks in both MMDT (r = 0.91
      0.97) and WRMT (r = 0.88-0.95). CONCLUSIONS: Caution is warranted in comparing
      scores from these 2 test variants. LEVEL OF EVIDENCE: 3b.

PMID- 28501481
TI  - Effect of Lymphadenectomy During Radical Nephroureterectomy in Locally Advanced
      Upper Tract Urothelial Carcinoma.
AB  - BACKGROUND: The role of lymph node dissection (LND) for upper tract urothelial
      carcinoma (UTUC) patients remains controversial. The aim of this study was to
      evaluate the effect of LND on clinical outcomes during radical nephroureterectomy
      (RNU) and to determine prognostic factors of survival. PATIENTS AND METHODS: From
      1985 to 2013, 404 patients with UTUC underwent RNU; 5 patients who received
      neoadjuvant chemotherapy were excluded. Among them, 182 (46%) were pathologically
      negative for lymph node metastasis (pN0), 177 (44%) were non-LND (pNx), and 40
      (10%) were positive for lymph nodes metastasis (pN1/2). RESULTS: The 5-year
      disease-free survival (DFS) and cancer-specific survival (CSS) rate were higher
      in pN0 patients than in pNx patients and in pN1/2 patients. According to
      multivariate analysis, non-LND was an independent predictive factor of DFS
      (hazard ratio [HR], 1.91; P = .004) and CSS (HR, 2.28; P = .003). In the subgroup
      with muscle-invasive UTUC, the 5-year DFS and CSS rates were higher in pN0
      patients than in pNx patients. However, there was no statistical difference
      between pN0 and pNx groups in terms of DFS and CSS in the pT2 cases. DFS and CSS
      times were significantly prolonged in the pN0 group in the locally advanced UTUC
      patients (>=pT3). CONCLUSION: In the >=pT3 subgroup, the 5-year DFS and CSS were
      significantly prolonged in the pN0 group, but there were no statistical
      differences between pN0 and pNx groups in terms of DFS and CSS in the pT2
      subgroup. LND for patients with locally advanced UTUC might improve disease
      prognosis.

PMID- 28501482
TI  - Ciproxifan improves cholinergic transmission, attenuates neuroinflammation and
      oxidative stress but does not reduce amyloid level in transgenic mice.
AB  - AIM: The present study is aimed to investigate the ability of ciproxifan, a
      histamine H3 receptor antagonist to inhibit beta-amyloid (Abeta)-induced
      neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND
      METHODS: In vitro studies was designed to evaluate the neuroprotective effects of
      ciproxifan in Abeta25-35 - induced SK-N-SH cells. For the in vivo study,
      ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days
      and behaviour was assessed using the radial arm maze (RAM). Brain tissues were
      collected to measure Abeta levels (Abeta1-40 and Abeta1-42), acetylcholine (ACh),
      acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO),
      antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1alpha, IL-1beta
      and IL-6), while plasma was collected to measure TGF-1beta. RESULTS: The in vitro
      studies demonstrated neuroprotective effect of ciproxifan by increasing cell
      viability and inhibiting reactive oxygen species (ROS) in Abeta25-35-induced SK-N
      SH cells. Ciproxifan significantly improved the behavioural parameters in RAM.
      Ciproxifan however, did not alter the Abeta levels in APP transgenic mice.
      Ciproxifan increased ACh and showed anti-oxidant properties by reducing NO and
      LPO levels as well as enhancing antioxidant levels. The neuroinflammatory
      analysis showed that ciproxifan reduced both COX-1 and COX-2 activities,
      decreased the level of pro-inflammatory cytokines IL-1alpha, IL-1beta and IL-6
      and increased the level of anti-inflammatory cytokine TGF-1beta. CONCLUSION: This
      present study provides scientific evidence of the use of ciproxifan via
      antioxidant and cholinergic pathways in the management of AD.

PMID- 28501484
TI  - Response to Letter to the Editor.

PMID- 28501483
TI  - Reversal of bioenergetics dysfunction by diphenyl diselenide is critical to
      protection against the acetaminophen-induced acute liver failure.
AB  - Physiopathological conditions such as acute liver failure (ALF) induced by
      acetaminophen (APAP) can often impair the mitochondrial bioenergetics. Diphenyl
      diselenide [(PhSe)2] has been shown protects against APAP-induced ALF. The
      present study aimed to clarify the signaling mechanism involved in the protection
      of bioenergetics dysfunction associated with ALF-induced by APAP overdose. Mice
      received APAP (600mg/kg) or (PhSe)2 (15.6mg/kg) alone, or APAP+(PhSe)2, all the
      solutions were administered by the intraperitoneal (i.p.). Samples of liver,
      blood and liver mitochondria were collected at 2 and 4h after APAP
      administration. APAP-induced ALF was able to induce ALF by means of alteration on
      liver injury biomarkers, increased Nitrite and Nitrate levels and the impairment
      of oxidative phosphorylation capacity (OXPHOS). In parallel, APAP overdose
      promoted activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and
      Heat shock protein 70 (HSP70) expression. (PhSe)2 was able to abolish the APAP
      induced decline of OXPHOS and changes on the Nrf2-ARE pathway. In addition,
      (PhSe)2 elevated the levels of peroxisome proliferator-activated receptor-gamma
      coactivator (PGC-1alpha), helping to restore the levels of nuclear respiratory
      factor 1 (NRF1) associated with mitochondrial biogenesis. In summary, the
      treatment with (PhSe)2 maintained mitochondrial function, promoted genes related
      to mitochondrial dynamic and demonstrating to play critical role in the
      modulation of cellular protective responses during ALF.

PMID- 28501486
TI  - Food additives: A special issue of the journal Food and Chemical Toxicology.

PMID- 28501485
TI  - Rapid genotyping of Legionella pneumophila serogroup 1 strains by a novel DNA
      microarray-based assay during the outbreak investigation in Warstein, Germany
      2013.
AB  - Between 1 August and 6 September 2013, an outbreak of Legionnaires' disease (LD)
      with 78 cases confirmed by positive urinary antigen tests occurred in Warstein,
      North Rhine-Westphalia, Germany. Legionella (L.) pneumophila, serogroup (Sg) 1,
      monoclonal antibody (mAb) subgroup Knoxville, sequence type (ST) 345, was
      identified as the epidemic strain. This strain was isolated from seven patients.
      To detect the source of the infection, epidemiological typing of clinical and
      environmental strains was performed in two consecutive steps. First, strains were
      typed by monoclonal antibodies. Indistinguishable strains were further subtyped
      by sequence-based typing (SBT) which is the internationally recognized standard
      method for epidemiological genotyping of L. pneumophila. In an early stage of the
      outbreak investigation, many environmental isolates were found to belong to the
      mAb subgroup Knoxville, but to two different STs, namely to ST 345, the epidemic
      strain, and to ST 600. A majority of environmental isolates belonged to ST 600
      whereas the epidemic ST 345 strain was less common in environmental samples. To
      rapidly distinguish both Knoxville strains, we applied a novel typing method
      based on DNA-hybridization on glass chips. The new assay can easily and rapidly
      discriminate L. pneumophila Sg 1 strains. Thus, we were able to quickly identify
      the sources harboring the epidemic strain, i.e., two cooling towers of different
      companies, the waste water treatment plants (WWTP) of the city and one company as
      well as water samples of the river Wester and its branches.

PMID- 28501487
TI  - Inhibition on cholinesterase and tyrosinase by alkaloids and phenolics from
      Aristotelia chilensis leaves.
AB  - It is reported in this study the effect of isolates from leaves of Aristotelia
      chilensis as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase
      (BChE) and tyrosinase enzymes. The aim of the paper was to evaluate the activity
      of A. chilensis towards different enzymes. In addition to pure compounds,
      extracts rich in alkaloids and phenolics were tested. The most active F5
      inhibited AChE (79.5% and 89.8% at 10.0 and 20.0 MUg/mL) and against BChE (89.5%
      and 97.8% at 10.0 and 20.0 MUg/mL), showing a strong mixed-type inhibition
      against AChE and BChE. F3 (a mixture of flavonoids and phenolics acids), showed
      IC50 of 90.7 and 59.6 MUg/mL of inhibitory activity against AChE and BChE,
      inhibiting the acetylcholinesterase competitively. Additionally, F3 showed and
      high potency as tyrosinase inhibitor with IC50 at 8.4 MUg/mL. Sample F4
      (anthocyanidins and phenolic composition) presented a complex, mixed-type
      inhibition of tyrosinase with a IC50 of 39.8 MUg/mL. The findings in this
      investigation show that this natural resource has a strong potential for future
      research in the search of new phytotherapeutic treatments for cholinergic
      deterioration ailments avoiding the side effects of synthetic drugs. This is the
      first report as cholinesterases and tyrosinase inhibitors of alkaloids and
      phenolics from A. chilensis leaves.

PMID- 28501488
TI  - Laminaria Japonica Polysaccharides effectively inhibited the growth of
      nasopharyngeal carcinoma cells in vivo and in vitro study.
AB  - AIMS: Laminaria Japonica Polysaccharides (LJP) is a kind of plant polysaccharide
      isolated from Laminaria Japonica Aresch. LJP has a variety of biological
      activity, including anti-tumor, improving immune function, anti-radiation and
      others. This study observed the biological activity of LJP in vitro and in vivo
      on human nasopharyngeal carcinoma(NPC), and the possible anticancer mechanism was
      explored. METHODS: Nasopharyngeal poorly differentiated squamous cell carcinoma
      cell lines CNE2 and HONE1 were used for the study. MTT method was used to detect
      the proliferation of HONE1 and CNE2 treated with gradient concentrations of LJP.
      The apoptosis of HONE1 treated with LJP was detected by annexin V-FITC/PI double
      staining method. HONE1 was used to establish subcutaneous implanted tumor model
      in nude mice. The changes of transplanted tumor volume and body weight of nude
      mice in each group were observed and recorded. The changes of the ultrastructure
      of transplanted tumor were observed by transmission electron microscope (TEM).
      RESULTS: MTT results showed that LJP has inhibitory effect on proliferation of
      both HONE1 and CNE2, and the effects were dosage-dependent; results of flow
      cytometry (FCM) analysis showed that, LJP could efficient induce apoptosis in
      HONE1, and apoptosis rate increased with the increase of LJP concentration. In
      vivo experiments, the inhibition rate was 33.7% (P<0.05) and 47% (P<0.01) in
      middle and high dose LJP group, respectively. TEM results suggested that the
      cancer cells in the transplanted tumor tissue treated with middle and high dose
      LJP presented unique apoptosis changes. CONCLUSIONS: LJP can effectively inhibit
      the growth of NPC cells. And it may be achieved by inducing apoptosis of NPC
      cells.

PMID- 28501489
TI  - Hydroxyethyl starch 130/0.4 compared with 0.9% NaCl administered to greyhounds
      with haemorrhagic shock.
AB  - OBJECTIVE: To determine the cardiovascular and acid-base effects of 6%
      hydroxyethyl starch (HES) 130/0.4 and 0.9% sodium chloride (NaCl) administered to
      anaesthetized greyhounds with haemorrhagic shock. STUDY DESIGN: Prospective,
      experimental, complete randomized block design. ANIMALS: Twelve healthy adult
      greyhounds. METHODS: After 60 minutes of isoflurane anaesthesia, 48 mL kg-1 of
      blood was removed to induce hypotension. Dogs were randomized to receive either
      20 mL kg-1 of HES 130/0.4 or 80 mL kg-1 of 0.9% NaCl over 20 minutes.
      Haemoglobin, arterial and central venous blood gas and electrolytes, lactate,
      mean arterial pressure (MAP) and cardiac index were measured at: T0, 60 minutes
      after induction of anaesthesia, immediately prior to blood removal; T1,
      immediately after blood removal; T2, immediately after fluid administration; and
      T3, 40 minutes after fluid administration. Oxygen extraction ratio (O2ER) was
      calculated at each sample time. RESULTS: O2ER increased at T1 and decreased at T2
      and T3, with no difference between the two groups. Dogs administered HES 130/0.4
      had higher lactate at T2 [mean (95% confidence interval) 1.3 (0.8-1.9) mmol L-1]
      than dogs administered 0.9% NaCl [0.8 (0.5-1.1) mmol L-1]; p = 0.045. Dogs
      administered HES 130/0.4 had a higher MAP at T3 [88 (74-102) mmHg] than dogs
      administered 0.9% NaCl [69 (60-79) mmHg]; p = 0.019. Dogs administered 0.9% NaCl
      were more acidaemic at T2 and T3, including higher hydrogen ion, lower
      bicarbonate, lower base excess and higher chloride concentrations. CONCLUSION:
      and clinical relevance The effect of 20 mL kg-1 of HES 130/0.4 on shock, as
      measured by O2ER, was no different than that of 80 mL kg-1 of 0.9% NaCl in dogs
      under general anaesthesia. Acidaemia in the NaCl group is likely attributable to
      hyperchloraemic metabolic acidosis from the larger volume administered.

PMID- 28501490
TI  - Colistin use in critically ill neonates: A case-control study.
AB  - BACKGROUND: The aim of this study was to assess the safety and efficacy of
      colistin use in critically ill neonates. METHODS: This was a case-control study
      that included newborn infants with proven or suspected nosocomial infections
      between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The
      clinical and laboratory characteristics and outcomes of patients who received
      colistin therapy were reviewed and compared to patients who were treated with
      antimicrobial agents other than colistin during the same period. RESULTS: Forty
      seven cases who received intravenous colistin (colistin group) and 59 control
      patients (control group) were included. There were no significant differences
      between the groups regarding outcomes and nephrotoxicity, including acute renal
      failure. Colistin therapy was associated with significantly reduced serum
      magnesium (1.38 +/- 0.39 mg/dL vs. 1.96 +/- 0.39 mg/dL, p < 0.001) and
      hypokalemia (46.8% vs. 25.4%, p = 0.026). The patients who received colistin also
      had longer hospital stays (43 (32-70) days vs. 39 (28-55) days, p = 0.047), a
      higher rate of previous carbapenem exposure (40.4% vs. 11.9%, p = 0.001), and a
      higher age at the onset of infection (13 (10-21) days vs. 11 (9-15) days, p =
      0.03). CONCLUSION: This study showed that colistin was both effective and safe
      for treating neonatal infections caused by multidrug-resistant gram-negative
      bacteria. However, intravenous colistin use was significantly associated with
      hypomagnesemia and hypokalemia.

PMID- 28501491
TI  - Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous
      meningitis using cerebrospinal fluid.
AB  - OBJECTIVE: Tuberculous meningitis (TBM) is the most severe form of extra
      pulmonary tuberculosis (TB) due to association of diseases with high rates of
      mortality and morbidity. Diagnosis continues to be a clinical challenge as
      microbiological confirmation is rare and time consuming resulting in delayed
      treatment. Xpert MTB/RIF assay is a rapid and simple test, which has been
      endorsed by World Health Organization as an initial diagnostic test for the
      diagnosis of TBM. However, evidence still lacks for its performance on
      cerebrospinal fluid (CSF) for the diagnosis of TBM especially from India.
      METHODS: A total of 267 CSF samples from patients with high clinico-radiological
      suspicion of TBM were included in this study. Ziehl-Neelsen (ZN) staining, BACTEC
      Mycobacterial Growth Indicator Tube (MGIT-960) culture system, and Xpert MTB/RIF
      assay (using cartridge version G4) were tested on all samples. RESULTS: Of total
      267 samples, all were negative for smear AFB and 52 (19.5%) were culture positive
      by MGIT-960 culture system. However, out of 52 (19.5%) cultures detected positive
      by MGIT-960, 5 (9.6%) were detected as resistant to rifampicin. Xpert MTB/RIF
      assay was positive in 38 (14.2%) samples and negative in 223 (83.5%) samples.
      Cartridge error was detected in 6 (2.2%) samples, which could not be repeated due
      to insufficient sample volume. The sensitivity and specificity of Xpert MTB/RIF
      assay in comparison to MGIT-960 was 55.1% (95%, CI: 40.2-69.3) and 94.8% (95%,
      CI: 90.9-97.4) respectively. Overall, Xpert MTB/RIF assay detected 38 (14.2%) as
      positive for MTB of which 4 (10.5%), 31 (81.6%) and 3 (7.9%) were found to be
      rifampicin resistant, sensitive and indeterminate respectively. CONCLUSION: Xpert
      MTB/RIF assay showed lower sensitivity as compared to MGIT 960 culture for the
      diagnosis of TBM from CSF samples.

PMID- 28501492
TI  - LDH inhibition impacts on heat shock response and induces senescence of
      hepatocellular carcinoma cells.
AB  - In normal cells, heat shock response (HSR) is rapidly induced in response to a
      variety of harmful conditions and represents one of the most efficient defense
      mechanism. In cancer tissues, constitutive activation converts HSR into a life
      threatening process, which plays a major role in helping cell survival and
      proliferation. Overexpression of heat shock proteins (HSPs) has been widely
      reported in human cancers and was found to correlate with tumor progression.
      Hepatocellular carcinoma is one of the conditions in which HSR activation was
      shown to have the highest clinical significance. Transcription of HSPs is induced
      by HSF-1, which also activates glycolytic metabolism and increases the expression
      of LDH-A, the master regulator of the Warburg effect. In this paper, we tried to
      explore the relationship between HSR and LDH-A. In cultured hepatocellular
      carcinoma cells, by using two enzyme inhibitors (oxamate and galloflavin), we
      found that the reduction of LDH-A activity led to decreased level and function of
      the major HSPs involved in tumorigenesis. Galloflavin (a polyphenol) also
      inhibited the ATPase activity of two of the examined HSPs. Finally, hindering HSR
      markedly lowered the alpha-fetoprotein cellular levels and induced senescence.
      Specific inhibitors of single HSPs are currently under evaluation in different
      neoplastic diseases. However, one of the effects usually observed during
      treatment is a compensatory elevation of other HSPs, which decreases treatment
      efficacy. Our results highlight a connection between LDH and HSR and suggest LDH
      inhibition as a way to globally impact on this tumor promoting process.

PMID- 28501493
TI  - Prophylactic warfarin post anterior ST-elevation myocardial infarction: A
      systematic review and meta-analysis.
AB  - OBJECTIVES: To determine the role of warfarin (WF) prophylaxis in the prevention
      of left ventricular thrombus (LVT) formation and subsequent embolic complications
      following an anterior ST elevation myocardial infarction (STEMI) complicated by
      reduced left ventricular ejection fraction (LVEF) and wall motion abnormalities.
      BACKGROUND: The role of oral anticoagulation prophylaxis, in addition to dual
      antiplatelet therapy (DAPT), in the current era of percutaneous coronary
      intervention has not been well studied, despite being a class IIb recommendation
      in the AHA/ACC STEMI guidelines. METHODS: The Cochrane search strategy was used
      to search PubMed, Embase and the Cochrane library for relevant results. Four
      studies, two retrospective, one prospective registry, and a randomized
      feasibility control trial met criteria for inclusion. Data was pooled using a
      random effects model and reported as odds ratios (OR) with their 95% confidence
      intervals (CI). Primary outcomes of interest were rate of stroke, major bleeding
      and mortality. RESULTS: Pooled analysis included 526 patients in the No WF group
      and 347 patients in the WF group. No statistical difference in rate of stroke
      (OR: 2.72 [95% CI: 0.47-15.88; p=0.21]) or mortality (OR: 1.50 [95% CI 0.29-7.71;
      p=0.63]) was observed. Major bleeding was significantly higher in the WF group
      (OR: 2.56 [95% CI: 1.34-4.89; p=0.004]). CONCLUSIONS: The routine use of DAPT and
      WF for prophylaxis against LVT formation following an anterior STEMI with
      associated decrease in LVEF and wall motion abnormalities, appears to result in
      no mortality benefit or reduction in stroke rates, but may increase the frequency
      of major bleeding.

PMID- 28501494
TI  - Focused microwave irradiation-assisted immunohistochemistry to study effects of
      ketamine on phospho-ERK expression in the mouse brain.
AB  - Ketamine produces rapid and long-lasting antidepressant effects in depressive
      patients. Preclinical studies demonstrate that ketamine stimulates AMPA receptor
      transmission and activates BDNF/TrkB-Akt/ERK-mTOR signaling cascades, leading to
      a sustained increase in synaptic protein synthesis and strengthening of synaptic
      plasticity, a potential mechanism underlying the antidepressant effects. The
      purpose of this study was to develop an immunohistochemistry (IHC) assay to map
      the distribution of extracellular signal-regulated kinase (ERK) phosphorylation
      in the mouse brain in response to systemic ketamine treatment. We established a
      focused microwave irradiation-assisted IHC assay to detect phosphorylated
      (phospho) proteins including phospho-ERK, phospho- cAMP-response- element-binding
      protein (CREB), phospho- glutamate receptor 1 (GluR1) and phospho-
      calcium/calmodulin-dependent protein kinase II (CaMKII) with greater sensitivity
      and reproducibility in comparison to conventional IHC methods. A single dose of
      ketamine produced a robust, dose- and time-dependent increase in phospho-ERK
      immunoreactive (phospho-ERK-ir) neurons in the medial prefrontal cortex (mPFC)
      and the central nucleus of the amygdala. Phospho-ERK-ir neurons in the mPFC were
      primarily located in the prelimbic and anterior cingulate subregions with the
      morphology resembling pyramidal neurons. An increase in phospho-ERK-ir was also
      observed in the brainstem dorsal raphe nucleus and locus coeruleus. The NMDA
      GluN2B subtype receptor antagonist Ro 25-6981 increased phospho-ERK expression in
      the brain in a similar pattern as ketamine. In summary, we have established a
      sensitive and reliable focused microwave irradiation-assisted IHC assay, and
      defined the activation pattern of ERK, in response to systemic ketamine and Ro 25
      6981 treatment, in brain regions that are potentially responsible for mediating
      the antidepressant effects.

PMID- 28501496
TI  - Improved life expectancy of people living with HIV: who is left behind?

PMID- 28501495
TI  - Survival of HIV-positive patients starting antiretroviral therapy between 1996
      and 2013: a collaborative analysis of cohort studies.
AB  - BACKGROUND: Health care for people living with HIV has improved substantially in
      the past two decades. Robust estimates of how these improvements have affected
      prognosis and life expectancy are of utmost importance to patients, clinicians,
      and health-care planners. We examined changes in 3 year survival and life
      expectancy of patients starting combination antiretroviral therapy (ART) between
      1996 and 2013. METHODS: We analysed data from 18 European and North American HIV
      1 cohorts. Patients (aged >=16 years) were eligible for this analysis if they had
      started ART with three or more drugs between 1996 and 2010 and had at least 3
      years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk
      group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause
      specific mortality hazard ratios (HRs) for the first year after ART initiation
      and the second and third years after ART initiation in four calendar periods
      (1996-99, 2000-03 [comparator], 2004-07, 2008-10). We estimated life expectancy
      by calendar period of initiation of ART. FINDINGS: 88 504 patients were included
      in our analyses, of whom 2106 died during the first year of ART and 2302 died
      during the second or third year of ART. Patients starting ART in 2008-10 had
      lower all-cause mortality in the first year after ART initiation than did
      patients starting ART in 2000-03 (adjusted HR 0.71, 95% CI 0.61-0.83). All-cause
      mortality in the second and third years after initiation of ART was also lower in
      patients who started ART in 2008-10 than in those who started in 2000-03 (0.57,
      0.49-0.67); this decrease was not fully explained by viral load and CD4 cell
      count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART
      in 2008-10 (vs 2000-03) in the first year (0.48, 0.34-0.67) and second and third
      years (0.29, 0.21-0.40) after initiation of ART. Between 1996 and 2010, life
      expectancy in 20-year-old patients starting ART increased by about 9 years in
      women and 10 years in men. INTERPRETATION: Even in the late ART era, survival
      during the first 3 years of ART continues to improve, which probably reflects
      transition to less toxic antiretroviral drugs, improved adherence, prophylactic
      measures, and management of comorbidity. Prognostic models and life expectancy
      estimates should be updated to account for these improvements. FUNDING: UK
      Medical Research Council, UK Department for International Development, EU EDCTP2
      programme.

PMID- 28501497
TI  - The Micro-Managing Fat: Exosomes as a New Messenger.
AB  - Brown fat secretes endocrine factors and exerts metabolic effects beyond
      thermogenesis. In addition to protein factors and bioactive lipids, recent work
      has revealed brown fat-derived miRNAs carried by exosomes as a new means of
      interorgan crosstalk, with potentially important implications for metabolic
      physiology and disease.

PMID- 28501498
TI  - The role of sleep in the plasticity of the olfactory system.
AB  - The central olfactory system mediates a variety of odor-guided behaviors crucial
      for maintenance of animal life. The olfactory neural circuit must be highly
      plastic to ensure that it responds appropriately to changing odor circumstances.
      Recent studies have revealed that the processing of odor information changes
      drastically during waking and sleep and that neural activity during sleep plays
      pivotal roles in the structural reorganization and functional plasticity of the
      olfactory system. While olfactory information from the external world is
      efficiently transferred to the olfactory cortex (OC) via the olfactory bulb (OB)
      during waking, this information flow is attenuated during slow-wave sleep: during
      slow-wave sleep, the OC neurons exhibit synchronous discharges without odor input
      under the entrainment of sharp waves in the local field potential recording. Top
      down transfer of sharp-wave activity to the OB during slow-wave sleep promotes
      structural reorganization of the OB neural circuit. Further, the activity of the
      OC during sleep is affected by the olfactory experience during prior waking
      period, and perturbation of the sleep activity disrupts proper olfactory memory.
      Thus, as is seen also in the hippocampus and neocortex, the neural activities of
      the olfactory system during sleep likely play essential roles in circuit
      reorganization and memory consolidation.

PMID- 28501499
TI  - Sleep in vertebrate and invertebrate animals, and insights into the function and
      evolution of sleep.
AB  - Many mammalian species, including humans, spend a substantial fraction of their
      life sleeping. Sleep deprivation in rats ultimately leads to death, indicating
      the essential role of sleep. Exactly why sleep is so essential, however, remains
      largely unknown. From an evolutionary point of view, almost all animal species
      that have been investigated exhibit sleep or sleep-like states, suggesting that
      sleep may benefit survival. In certain mammalian and avian species, sleep can be
      further divided into at least two stages, rapid eye movement (REM) sleep and non
      REM sleep. In addition to a widely conserved role for sleep, these individual
      sleep stages may have roles unique to these animals. The recent use of state-of
      the-art techniques, including optogenetics and chemogenetics, has greatly
      broadened our understanding of the neural mechanisms of sleep regulation,
      allowing us to address the function of sleep. Studies focusing on non-mammalian
      animals species have also provided novel insights into the evolution of sleep.
      This review provides a comprehensive overview regarding the current knowledge of
      the function and evolution of sleep.

PMID- 28501500
TI  - It's about time: The development and validation of a rapid optimized single
      antigen bead (ROB) assay protocol for LABScreen.
AB  - The LABScreen single antigen bead assay (SAB) is a method widely used for the
      identification and monitoring of human leukocyte antigen (HLA) antibodies in
      patients pre-and post-transplant. While accurate testing of patient samples is
      key for optimal patient care, time can also be important, especially during
      deceased donor workups or post-transplant assessments. Here we describe the
      development and validation of the Rapid Optimized SAB (ROB) protocol, a modified
      version of the One Lambda LABScreen SAB (OLSAB) procedure, which reduces assay
      time from 85 to 25min (>70% reduction) without impacting assay quality or
      sensitivity. Optimization steps included shortened centrifugation cycles and
      reduced serum and secondary antibody incubation times in combination with
      increased secondary antibody concentration. Linear regression analysis of
      baseline median fluorescence intensity (MFI) values showed excellent correlation
      between the ROB and OLSAB protocols (r2>0.98) for both class I and class II
      antibodies in 58 sera tested in two HLA laboratories. Importantly, the ROB
      protocol demonstrated a trend towards improved inter-laboratory MFI concordance
      when compared to the OLSAB procedure (r2=0.9816 vs 0.9451), especially for HLA
      antibody specificities in the 500-2000 MFI range (r2=0.7824 vs 0.6313).
      Implementation of the ROB protocol will expedite HLA antibody testing and may
      improve reproducibility of the SAB assay.

PMID- 28501501
TI  - Anti-tumor effects of differentiation-inducing factor-1 in malignant melanoma:
      GSK-3-mediated inhibition of cell proliferation and GSK-3-independent suppression
      of cell migration and invasion.
AB  - Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum
      strongly inhibits the proliferation of various mammalian cells through the
      activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel
      anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti
      proliferative, anti-migratory, and anti-invasive effects on melanoma cells using
      in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1
      and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human
      (A2058) malignant melanoma cells, and thereby strongly inhibited their
      proliferation. DIF-1 suppressed the canonical Wnt signaling pathway by lowering
      the expression levels of transcription factor 7-like 2 and beta-catenin, key
      transcription factors in this pathway. DIF-1 also inhibited cell migration and
      invasion, reducing the expression of matrix metalloproteinase-2; however, this
      effect was not dependent on GSK-3 activity. In a mouse lung tumor formation
      model, repeated oral administrations of DIF-1 markedly reduced melanoma colony
      formation in the lung. These results suggest that DIF-1 inhibits cell
      proliferation by a GSK-3-dependent mechanism and suppresses cell migration and
      invasion by a GSK-3-independent mechanism. Therefore, DIF-1 may have a potential
      as a novel anti-cancer agent for the treatment of malignant melanoma.

PMID- 28501502
TI  - Urtica dioica Extract Inhibits Proliferation and Induces Apoptosis and Related
      Gene Expression of Breast Cancer Cells In Vitro and In Vivo.
AB  - INTRODUCTION: Currently, because the prevalence of breast cancer and its
      consequent mortality has increased enormously in the female population, a number
      of studies have been designed to identify natural products with special antitumor
      properties. The main purpose of the present study was to determine the effect of
      Urtica dioica on triggering apoptosis and diminishing growth, size, and weight of
      the tumor in an allograft model of BALB/c mice. MATERIALS AND METHODS: In the
      present study, a BALB/c mouse model of breast cancer (4T1) was used. After
      emergence of tumor, 2 groups of mice received the extract, 1 group at a dose of
      10 mg/kg and 1 group at a dose of 20 mg/kg, by intraperitoneal injection for 28
      days. During the test and after removal of the tumor mass, the size and weight of
      the tumor were measured. To assess the induction of apoptosis in the cancer
      cells, the TUNEL (terminal deoxynucleotidyl transferase deoxyuridine triphosphate
      nick-end labeling) assay was performed. The Ki-67 test was used to evaluate tumor
      proliferation. RESULTS: The results showed that the tumor size in the mice
      treated with the extract decreased significantly. The weight of the tumor mass in
      the treated mice after resection was less than that in the control group. The
      TUNEL assay findings revealed that apoptosis occurred in the treated group. The
      Ki-67 test findings also demonstrated that administration of the extract
      suppressed the growth of tumor cells. CONCLUSION: These results suggest that U.
      dioica extract can decrease the growth of breast tumors and induce apoptosis in
      tumor cells; thus, it might represent an ideal therapeutic tool for breast
      cancer.

PMID- 28501504
TI  - Transmission of Borrelia miyamotoi sensu lato relapsing fever group spirochetes
      in relation to duration of attachment by Ixodes scapularis nymphs.
AB  - Borrelia miyamotoi sensu lato relapsing fever group spirochetes are emerging as
      causative agents of human illness (Borrelia miyamotoi disease) in the United
      States. Host-seeking Ixodes scapularis ticks are naturally infected with these
      spirochetes in the eastern United States and experimentally capable of
      transmitting B. miyamotoi. However, the duration of time required from tick
      attachment to spirochete transmission has yet to be determined. We therefore
      conducted a study to assess spirochete transmission by single transovarially
      infected I. scapularis nymphs to outbred white mice at three time points post
      attachment (24, 48, and 72h) and for a complete feed (>72-96h). Based on
      detection of B. miyamotoi DNA from the blood of mice fed on by an infected nymph,
      the probability of spirochete transmission increased from 10% by 24h of
      attachment (evidence of infection in 3/30 mice) to 31% by 48h (11/35 mice), 63%
      by 72h (22/35 mice), and 73% for a complete feed (22/30 mice). We conclude that
      (i) single I. scapularis nymphs effectively transmit B. miyamotoi relapsing fever
      group spirochetes while feeding, (ii) transmission can occur within the first 24h
      of nymphal attachment, and (iii) the probability of transmission increases with
      the duration of nymphal attachment.

PMID- 28501503
TI  - Detection and molecular characterization of Babesia, Theileria, and Hepatozoon
      species in hard ticks collected from Kagoshima, the southern region in Japan.
AB  - To reveal the distribution of tick-borne parasites, we established a novel nested
      polymerase chain reaction (PCR) system to detect the most common agents of tick
      borne parasitic diseases, namely Babesia, Theileria, and Hepatozoon parasites. We
      collected host-seeking or animal-feeding ticks in Kagoshima Prefecture, the
      southernmost region of Kyusyu Island in southwestern Japan. Twenty of the total
      of 776 tick samples displayed a specific band of the appropriate size
      (approximately 1.4-1.6kbp) for the 18S rRNA genes in the novel nested PCR
      (20/776: 2.58%). These PCR products have individual sequences of Babesia spp.
      (from 8 ticks), Theileria spp. (from 9 ticks: one tick sample including at least
      two Theileria spp. sequences), and Hepatozoon spp. (from 3 ticks). Phylogenetic
      analyses revealed that these sequences were close to those of undescribed Babesia
      spp. detected in feral raccoons in Japan (5 sequences; 3 sequences being
      identical), Babesia gibsoni-like parasites detected in pigs in China (3
      sequences; all sequences being identical), Theileria spp. detected in sika deer
      in Japan and China (10 sequences; 2 sequences being identical), Hepatozoon canis
      (one sequence), and Hepatozoon spp. detected in Japanese martens in Japan (two
      sequences). In summary, we showed that various tick-borne parasites exist in
      Kagoshima, the southern region in Japan by using the novel nested PCR system.
      These including undescribed species such as Babesia gibsoni-like parasites
      previously detected in pigs in China. Importantly, our results revealed new
      combinations of ticks and protozoan parasites in southern Japan. The results of
      this study will aid in the recognition of potential parasitic animal diseases
      caused by tick-borne parasites.

PMID- 28501505
TI  - Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar
      formation after ischemia-reperfusion brain injury.
AB  - Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial
      scar can inhibit axonal regeneration during the recovery phase. It has
      demonstrated that sevoflurane has neuroprotective effects against ischemic
      stroke, but its effects on ischemia-induced formation of astrogliosis and glial
      scar are unknown. This study was designed to investigate the effect of
      sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic
      stroke model both in vivo and in vitro. The results showed that 2.5% of
      sevoflurane postconditioning could significantly reduce infarction volume and
      improve neurologic deficits. And it could also decrease the expression of the
      glial scar marker glial fibrillary acidic protein (GFAP), neurocan and phosphacan
      in the peri-infarct region and markedly reduce the thickness of glial scar after
      ischemia/reperfusion (I/R). Consistent with the in vivo data, in the oxygen and
      glucose deprivation/reoxygenation (OGD/Re) model, sevoflurane postconditioning
      could protect astrocyte against OGD/Re-induced injury, decrease the expression of
      GFAP, neurocan and phosphacan. Further studies demonstrated that sevoflurane
      postconditioning could down-regulate the expression of Lamp1 and active cathepsin
      B, and block I/R or OGD/Re-induced release of cathepsin B from the lysosomes into
      cytoplasm. In order to confirm whether inhibition of cathepsin B could attenuate
      the formation of glial scar, we used cathepsin B inhibitor CA-074Me as a positive
      control. The results showed that inhibition of cathepsin B could decrease the
      expression of GFAP, neurocan and phosphacan. Taken together, sevoflurane
      postconditioning can attenuate astrogliosis and glial scar formation after
      ischemic stroke, associating with inhibition of the activation and release of
      lysosomal cathepsin B.

PMID- 28501507
TI  - Peering over the chasm: Diffusion of prostate radiation therapy
      hypofractionation.

PMID- 28501506
TI  - Defective neuronal migration and inhibition of bipolar to multipolar transition
      of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the
      developing mouse neocortex.
AB  - Brain developmental disorders such as lissencephaly can result from faulty
      neuronal migration and differentiation during the formation of the mammalian
      neocortex. The cerebral cortex is a modular structure, where developmentally,
      newborn neurons are generated as a neuro-epithelial sheet and subsequently
      differentiate, migrate and organize into their final positions in the cerebral
      cortical plate via a process involving both tangential and radial migration. The
      specific role of Mest, an imprinted gene, in neuronal migration has not been
      previously studied. In this work, we reduced expression of Mest with in utero
      electroporation of neuronal progenitors in the developing embryonic mouse
      neocortex. Reduction of Mest levels by shRNA significantly reduced the number of
      neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the
      transition of bipolar neurons into multipolar neurons migrating out of the sub
      ventricular zone region. The migrating neurons also adopted a more tangential
      migration pattern upon knockdown of the Mest message, losing their potential to
      attach to radial glia cells, required for radial migration. The differentiation
      and migration properties of neurons via Wnt-Akt signaling were affected by Mest
      changes. In addition, miR-335, encoded in a Mest gene intron, was identified as
      being responsible for blocking the default tangential migration of the neurons.
      Our results suggest that Mest and its intron product, miR-335, play important
      roles in neuronal migration with Mest regulating the morphological transition of
      primary neurons required in the formation of the mammalian neocortex.

PMID- 28501508
TI  - Military metaphors in oncology: Let's not fight about this.

PMID- 28501509
TI  - Designer outer membrane vesicles as immunomodulatory systems - Reprogramming
      bacteria for vaccine delivery.
AB  - Vaccines often require adjuvants to be effective. Traditional adjuvants, like
      alum, activate the immune response but in an uncontrolled way. Newer adjuvants
      help to direct the immune response in a more coordinated fashion. Here, we review
      the opportunity to use the outer membrane vesicles (OMVs) of bacteria as a way to
      modulate the immune response toward making more effective vaccines. This review
      outlines the different types of OMVs that have been investigated for vaccine
      delivery and how they are produced. Because OMVs are derived from bacteria, they
      have compositions that may not be compatible with parenteral delivery in humans;
      therefore, we also review the strategies brought to bear to detoxify OMVs while
      maintaining an adjuvant profile. OMV-based vaccines can be derived from the
      pathogens themselves, or can be used as surrogate constructs to mimic a pathogen
      through the heterologous expression of specific antigens in a desired host source
      strain, and approaches to doing so are reviewed. Additionally, the emerging area
      of engineered pathogen-specific carbohydrate sequences, or glycosylated OMVs is
      reviewed and contrasted with protein antigen delivery. Existing OMV-based
      vaccines as well as their routes of administration round out the text. Overall,
      this is an exciting time in the OMV field as it matures and leads to more
      effective and targeted ways to induce desired pathogen-specific immune responses.

PMID- 28501511
TI  - Identification of quinazoline based inhibitors of IRAK4 for the treatment of
      inflammation.
AB  - Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R
      and TLR based signaling. Therefore selective inhibition of the kinase activity of
      this protein represents an attractive target for the treatment of inflammatory
      diseases. Medicinal chemistry optimization of high throughput screening (HTS)
      hits with the help of structure based drug design led to the identification of
      orally-bioavailable quinazoline based IRAK4 inhibitors with excellent
      pharmacokinetic profile and kinase selectivity. These highly selective IRAK4
      compounds show activity in vivo via oral dosing in a TLR7 driven model of
      inflammation.

PMID- 28501512
TI  - Anti-influenza activity of monoterpene-containing substituted coumarins.
AB  - Compounds simultaneously carrying the monoterpene and coumarin moieties have been
      tested for cytotoxicity and inhibition of activity against influenza virus
      A/California/07/09 (H1N1)pdm09. The structure of substituents in the coumarin
      framework, as well as the structure and the absolute configuration of the
      monoterpenoid moiety, are shown to significantly influence the anti-influenza
      activity and cytotoxicity of the compounds under study. The compounds with a
      bicyclic pinane framework exhibit the highest selectivity indices (the ratios
      between the cytotoxicity and the active dose). The derivative of (-)-myrtenol
      15c, which is characterized by promising activity, low cytotoxicity, and
      synthetic accessibility, has the greatest potential among this group of
      compounds. It exhibited the highest activity when added to the infected cell
      culture at early stages of viral reproduction.

PMID- 28501513
TI  - QSAR studies of the bioactivity of hepatitis C virus (HCV) NS3/4A protease
      inhibitors by multiple linear regression (MLR) and support vector machine (SVM).
AB  - In this study, quantitative structure-activity relationship (QSAR) models using
      various descriptor sets and training/test set selection methods were explored to
      predict the bioactivity of hepatitis C virus (HCV) NS3/4A protease inhibitors by
      using a multiple linear regression (MLR) and a support vector machine (SVM)
      method. 512 HCV NS3/4A protease inhibitors and their IC50 values which were
      determined by the same FRET assay were collected from the reported literature to
      build a dataset. All the inhibitors were represented with selected nine global
      and 12 2D property-weighted autocorrelation descriptors calculated from the
      program CORINA Symphony. The dataset was divided into a training set and a test
      set by a random and a Kohonen's self-organizing map (SOM) method. The correlation
      coefficients (r2) of training sets and test sets were 0.75 and 0.72 for the best
      MLR model, 0.87 and 0.85 for the best SVM model, respectively. In addition, a
      series of sub-dataset models were also developed. The performances of all the
      best sub-dataset models were better than those of the whole dataset models. We
      believe that the combination of the best sub- and whole dataset SVM models can be
      used as reliable lead designing tools for new NS3/4A protease inhibitors
      scaffolds in a drug discovery pipeline.

PMID- 28501510
TI  - Surface engineering for lymphocyte programming.
AB  - The once nascent field of immunoengineering has recently blossomed to include
      approaches to deliver and present biomolecules to program diverse populations of
      lymphocytes to fight disease. Building upon improved understanding of the
      molecular and physical mechanics of lymphocyte activation, varied strategies for
      engineering surfaces to activate and deactivate T-Cells, B-Cells and natural
      killer cells are in preclinical and clinical development. Surfaces have been
      engineered at the molecular level in terms of the presence of specific biological
      factors, their arrangement on a surface, and their diffusivity to elicit specific
      lymphocyte fates. In addition, the physical and mechanical characteristics of the
      surface including shape, anisotropy, and rigidity of particles for lymphocyte
      activation have been fine-tuned. Utilizing these strategies, acellular systems
      have been engineered for the expansion of T-Cells and natural killer cells to
      clinically relevant levels for cancer therapies as well as engineered to program
      B-Cells to better combat infectious diseases.

PMID- 28501514
TI  - Stabilizing HDAC11 with SAHA to assay slow-binding benzamide inhibitors.
AB  - Among 18 human histone deacetylases (HDAC), HDAC11 is least studied. MS275, a
      benzamide HDAC inhibitor (HDACi), was stereotypically considered to selectively
      target Class I HDACs. We verified this slow-binding inhibitor also targeted
      HDAC11. In a traditional enzyme based assay, MS275 at low concentrations
      surprisingly behaved as an agonist. This was attributed to the poor stability of
      HDAC11 which lost 40% activity in 3h at 37 degrees C. By adding 0.2MUM SAHA,
      HDAC11 activity was stabilized during the 3-h assay period. Since 0.2MUM SAHA
      inhibited 50% HDAC11 activity, the apparent IC50' of MS275 was adjusted to the
      true IC50=0.65MUM. Finally, the new method demonstrated its superiority in one
      dose-screening assays by decreasing false negative results. This work highlighted
      an optimized strategy to assay slow-binding inhibitors of unstable proteins with
      known fast-binding inhibitors. It should be especially useful in a hit-discovery
      stage to find moderate potent compounds.

PMID- 28501515
TI  - Shrimp humoral responses against pathogens: antimicrobial peptides and
      melanization.
AB  - Diseases have caused tremendous economic losses and become the major problem
      threatening the sustainable development of shrimp aquaculture. The knowledge of
      host defense mechanisms against invading pathogens is essential for the
      implementation of efficient strategies to prevent disease outbreaks. Like other
      invertebrates, shrimp rely on the innate immune system to defend themselves
      against a range of microbes by recognizing and destroying them through cellular
      and humoral immune responses. Detection of microbial pathogens triggers the
      signal transduction pathways including the NF-kappaB signaling, Toll and Imd
      pathways, resulting in the activation of genes involved in host defense
      responses. In this review, we update the discovery of components of the Toll and
      Imd pathways in shrimp and their participation in the regulation of shrimp
      antimicrobial peptide (AMP) synthesis. We also focus on a recent progress on the
      two most powerful and the best-studied shrimp humoral responses: AMPs and
      melanization. Shrimp AMPs are mainly cationic peptides with sequence diversity
      which endues them the broad range of activities against microorganisms.
      Melanization, regulated by the prophenoloxidase activating cascade, also plays a
      crucial role in killing and sequestration of invading pathogens. The progress and
      emerging research on mechanisms and functional characterization of components of
      these two indispensable humoral responses in shrimp immunity are summarized and
      discussed. Interestingly, the pattern recognition protein (PRP) crosstalk is
      evidenced between the proPO activating cascade and the AMP synthesis pathways in
      shrimp, which enables the innate immune system to build up efficient immune
      responses.

PMID- 28501516
TI  - Is dual inhibition of metalloenzymes HDAC-8 and MMP-2 a potential pharmacological
      target to combat hematological malignancies?
AB  - For the last three decades, metalloenzymes such as histone deacetylases (HDACs)
      and matrix metalloproteinases (MMPs) have been identified in promoting solid as
      well as hematological carcinogenesis. Histone deacetylase 8 (HDAC-8), a class I
      HDAC enzyme, may serve as 'epigenetic player' that affects in the regulation of
      transcription factors and alters the structure of chromosome associated with
      tumorigenesis. It is established that the influence of MMP-2 in invasion,
      metastasis and angiogenenic events of hematological malignancies may be
      suppressed by HDAC inhibitors through reversion-inducing-cysteine-rich protein
      with kazal motifs (RECK) protein. Therefore, the isoform-specific HDAC-8 and MMP
      2 inhibitors may provide synergistic medicinal benefit in leukemia. However, a
      paucity of articles is available on dual acting HDAC-8/MMP-2 inhibitors. In this
      circumstance, a lot of works are still necessary to identify novel dual HDAC
      8/MMP-2 inhibitors and this review will surely provide an initial idea regarding
      the utility of designing such type of dual inhibitors. Here, the importance of
      MMP-2 and HDAC-8 inhibition in hematological malignancies are focussed for the
      first time as per our knowledge along with the structure-activity relationships
      (SARs) of a handful of molecules, some of which were synthesised in-house, have
      been highlighted that will inspire more interactions between the medicinal
      chemistry and biology community to harness their expertise in design and
      discovery of the better acting dual inhibitors in future.

PMID- 28501517
TI  - Nanoparticles for modulating tumor microenvironment to improve drug delivery and
      tumor therapy.
AB  - Tumor microenvironment (TME) plays a critical role in tumorigenesis, tumor
      invasion and metastasis. TME is composed of stroma, endothelial cells, pericytes,
      fibroblasts, smooth muscle cells, and immune cells, which is characterized by
      hypoxia, acidosis, and high interstitial fluid pressure. Due to the important
      role of TME, we firstly reviewed the composition of TME and discussed the impact
      of TME on tumor progression, drug and nanoparticle delivery. Next, we reviewed
      current strategies developed to modulate TME, including modulating tumor
      vasculature permeability, tumor associated macrophage phenotypes, tumor
      associated fibroblasts, tumor stroma components, tumor hypoxia, and multiple
      interventions simultaneously. Also, potential problems and future directions of
      TME modulation strategy have been discussed.

PMID- 28501518
TI  - Cannabidiol in medical marijuana: Research vistas and potential opportunities.
AB  - The high and increasing prevalence of medical marijuana consumption in the
      general population invites the need for quality evidence regarding its safety and
      efficacy. Herein, we synthesize extant literature pertaining to the
      phytocannabinoid cannabidiol (CBD) and its brain effects. The principle
      phytocannabinoid Delta9-tetrahydrocannabinol (Delta9-THC) and CBD are the major
      pharmacologically active cannabinoids. The effect of CBD on brain systems as well
      as on phenomenological measures (e.g. cognitive function) are distinct and in
      many cases opposite to that of Delta9-THC. Cannabidiol is without euphoriant
      properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti
      inflammatory properties. It is essential to parcellate phytocannabinoids into
      their constituent moieties as the most abundant cannabinoid have differential
      effects on physiologic systems in psychopathology measures. Disparate findings
      and reports related to effects of cannabis consumption reflect differential
      relative concentration of Delta9-THC and CBD. Existing literature,
      notwithstanding its deficiencies, provides empirical support for the hypothesis
      that CBD may exert beneficial effects on brain effector systems/substrates
      subserving domain-based phenomenology. Interventional studies with purified CBD
      are warranted with a call to target-engagement proof-of-principle studies using
      the research domain criteria (RDoC) framework.

PMID- 28501519
TI  - The Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac
      Sarcoidosis.
AB  - BACKGROUND: Autopsy reports suggest that cardiac sarcoidosis occurs in 20 to 25%
      of patients with pulmonary sarcoidosis, yet the clinical ante-mortem diagnosis is
      made in only 5% of cases. Current diagnostic algorithms are complex and lack
      sensitivity. Cardiac Magnetic Resonance imaging (CMR) provides an opportunity to
      detect myocardial involvement in sarcoidosis. The aim of this study is to
      determine the prevalence and clinical significance of late gadolinium enhancement
      (LGE) on CMR in patients with sarcoidosis. METHODS: Consecutive patients with
      biopsy-proven sarcoidosis undergoing CMR were retrospectively evaluated for
      cardiac sarcoidosis. Medical records were correlated with CMR. RESULTS: Forty-six
      patients were evaluated. Late gadolinium enhancement was present in 22%,
      indicating myocardial involvement, and 70% had corresponding hyper-intense T2
      signal indicating active inflammation. Late gadolinium enhancement was 18%+/-9.7%
      of overall left ventricular (LV) mass and most commonly located in the basal to
      mid septum. There was no association between LGE and cardiovascular symptoms or
      pulmonary stage. Eighty per cent of patients with LGE did not fulfill
      conventional diagnostic criteria for cardiac sarcoidosis. However, LGE was
      associated with clinically significant arrhythmia (p<0.01) and a lower LVEF
      (p=0.04). CONCLUSIONS: Using CMR, we identified a higher prevalence of cardiac
      sarcoidosis than previously reported clinical studies, a prevalence which is more
      consistent with autopsy data. The presence of LGE was highly correlated with
      clinically significant arrhythmias and lower LVEF.

PMID- 28501520
TI  - Can Heart Failure With Preserved Ejection Fraction Shed Light on the Mortality
      Readmissions Paradox?

PMID- 28501521
TI  - Associations Between Short or Long Length of Stay and 30-Day Readmission and
      Mortality in Hospitalized Patients With Heart Failure.
AB  - OBJECTIVES: This study sought to examine the associations between heart failure
      (HF)-related hospital length of stay and 30-day readmissions and HF hospital
      length of stay and mortality rates. BACKGROUND: Although reducing HF readmission
      and mortality rates are health care priorities, how HF-related hospital length of
      stay affects these outcomes is not fully known. METHODS: A population-level,
      multicenter cohort study of 58,230 patients with HF (age >65 years) was conducted
      in Ontario, Canada between April 1, 2003 and March 31, 2012. RESULTS: When length
      of stay was modeled as continuous variable, its association with the rate of
      cardiovascular readmission was nonlinear (p < 0.001 for nonlinearity) and U
      shaped. When analyzed as a categorical variable, there was a higher rate of
      cardiovascular readmission for short (1 to 2 days; adjusted hazard ratio [HR]:
      1.12; 95% confidence interval [CI]: 1.04 to 1.21; p = 0.003) and long (9 to 14
      days; HR: 1.11; 95% CI: 1.04 to 1.19; p = 0.002) lengths of stay as compared with
      5 to 6 days (reference). Hospital readmissions for HF demonstrated a similar
      nonlinear (p = 0.005 for nonlinearity) U-shaped relationship with increased rates
      for short (HR: 1.15; 95% CI: 1.04 to 1.27; p = 0.006) and long (HR: 1.14; 95% CI:
      1.04 to 1.25; p = 0.004) lengths of stay. Noncardiovascular readmissions
      demonstrated increased rates with long (HR: 1.17; 95% CI: 1.07 to 1.29; p <
      0.001) and decreased rates with short (HR: 0.87; 95% CI: 0.79 to 0.96; p = 0.006)
      lengths of stay (p = 0.53 for nonlinearity). The 30-day mortality risk was
      highest after a long length of stay (HR: 1.28; 95% CI: 1.14 to 1.43; p < 0.001).
      CONCLUSIONS: A short length of stay after hospitalization for HF is associated
      with increased rates of cardiovascular and HF readmissions but lower rates of
      noncardiovascular readmissions. A long length of stay is associated with
      increased rates of all types of readmission and mortality.

PMID- 28501522
TI  - Long-Term Effects of Flosequinan on the Morbidity and Mortality of Patients With
      Severe Chronic Heart Failure: Primary Results of the PROFILE Trial After 24
      Years.
AB  - OBJECTIVES: The purpose of this clinical trial was to evaluate the long-term
      effects of flosequinan on the morbidity and mortality of patients with severe
      chronic heart failure. BACKGROUND: Flosequinan was the first oral vasodilator to
      be used in the clinic to augment the effects of digitalis, diuretics, and
      angiotensin-converting enzyme inhibitors in heart failure. However, the drug
      activated neurohormonal systems and exerted both positive inotropic and
      chronotropic effects, raising concerns about its safety during long-term use.
      METHODS: Following a run-in period designed to minimize the risk of tachycardia,
      we randomly assigned 2,354 patients in New York Heart Association functional
      class III to IV heart failure and with an ejection fraction <=35% to receive long
      term treatment with placebo or flosequinan (75 or 100 mg/day) in addition to
      their usual therapy. The primary outcome was all-cause mortality. RESULTS: The
      trial was terminated after a recommendation of the Data and Safety Monitoring
      Board, because during an average of 10 months of follow-up, 192 patients died in
      the placebo group and 255 patients died in the flosequinan group (hazard ratio:
      1.39, 95% confidence interval: 1.15 to 1.67; p = 0.0006). Flosequinan also
      increased the risk of disease progression, which was paralleled by drug-related
      increases in heart rate and neurohormonal activation. However, during the first
      month, patients in the flosequinan group were more likely to report an
      improvement in well-being and less likely to experience worsening heart failure.
      Similarly, during the month following drug withdrawal at the end of the trial,
      patients withdrawn from flosequinan were more likely than those withdrawn from
      placebo to report symptoms of or to require treatment for worsening heart
      failure. CONCLUSIONS: Although flosequinan produced meaningful symptomatic
      benefits during short- and long-term treatment, the drug increased the risk of
      death in patients with severe chronic heart failure.

PMID- 28501524
TI  - Holding the Readmission Gates: Incentivizing Quality and Cost-Effective Care for
      Heart Failure.

PMID- 28501523
TI  - A New Clinically Applicable Measure of Functional Status in Patients With Heart
      Failure: The 60-Foot Walk Test.
AB  - OBJECTIVES: This study reports the development and predictive value of the 60
      foot walk test (60ftWT), a brief functional status measure for patients with
      heart failure (HF). The goal was to develop a test suitable for clinical settings
      and appropriate for patients with walking impairments. BACKGROUND: The 6-min walk
      test (6MWT) has considerable predictive value, but requires a long walking course
      and has limited utility in patients with mobility-related comorbidities. A
      shorter, more clinically practical test is therefore needed. METHODS: A total of
      144 patients (age 57.4 +/- 11.4 years; 111 males) with symptomatic HF received
      baseline assessments using the 60ftWT, 6MWT, and self-reported symptom and health
      status. Patients were tested 3 months later to determine stability of
      assessments. HF hospitalizations or death from any cause were recorded for 3.5
      years following baseline. RESULTS: Median 60ftWT completion time was 26 s
      (interquartile range: 22 to 31 s). Longer 60ftWT time was associated with shorter
      6MWT distance (r = -0.75; p < 0.001), and with higher symptom severity at
      baseline (r = -0.40; p < 0.001). Longer 60ftWT times also predicted increases in
      6MWT and symptoms from baseline to 3 months (p < 0.01). Both WTs predicted long
      term clinical outcomes, with patients taking longer than 31 s to complete the
      60ftWT at greatest risk for HF hospitalization or death (hazard ratio: 2.13; 95%
      confidence interval: 1.18 to 3.84; p = 0.01). CONCLUSIONS: The 60ftWT is an
      easily administered functional status measure that predicts adverse events,
      symptoms, and health status. It has the potential for considerable clinical
      utility to help identify patients at risk for future events and to calibrate
      treatments designed to improve functional status and quality of life.

PMID- 28501525
TI  - Tetralogy of Fallow: Four Trials and Tribulations.

PMID- 28501526
TI  - Do We Need Another Walking Test?

PMID- 28501529
TI  - Hepatocellular carcinoma diagnosis and surveillance: Socioeconomic factors don't
      seem to matter, unless you are an immigrant.

PMID- 28501527
TI  - Race/Ethnic Differences in Outcomes Among Hospitalized Medicare Patients With
      Heart Failure and Preserved Ejection Fraction.
AB  - OBJECTIVES: This study analyzed HFpEF patient characteristics and clinical
      outcomes according to race/ethnicity and adjusted for patient and hospital
      characteristics along with socioeconomic status (SES). BACKGROUND: The proportion
      of hospitalizations for heart failure with preserved ejection fraction (HFpEF)
      has increased over the last decade. Whether the short- and long-term outcomes
      differ between racial/ethnic groups is not well described. METHODS: The Get With
      The Guidelines-Heart Failure registry was linked to Medicare administrative data
      to identify hospitalized patients with HFpEF >=65 years of age with left
      ventricular ejection fraction >=50% between 2006 and 2014. Cox proportional
      hazards models were used to report hazard ratios (HRs) for 30-day and 1-year
      readmission and mortality rates with sequential adjustments for patient
      characteristics, hospital characteristics, and SES. RESULTS: The final cohort
      included 53,065 patients with HFpEF. Overall 30-day mortality was 5.87%; at 1
      year, it was 33.1%. The 30-day all-cause readmission rate was 22.2%, and it was
      67.0% at 1 year. After adjusting for patient characteristics, hospital
      characteristics, and SES, 30-day mortality was lower for black patients (HR:
      0.84; 95% confidence interval [CI]: 0.71 to 0.98; p = 0.031) and Hispanic
      patients (HR: 0.78; 95% CI: 0.64 to 0.96; p = 0.017) compared with white
      patients. One-year mortality was lower for black patients (HR: 0.93; 95% CI: 0.87
      to 0.99; p = 0.031), Hispanic patients (HR: 0.83; 95% CI: 0.75 to 0.91; p <
      0.001), and Asian patients (HR: 0.76; 95% CI: 0.66 to 0.88; p < 0.001) compared
      with white patients. Black patients had a higher risk of readmission at 30 days
      (HR: 1.09; 95% CI: 1.02 to 1.16; p = 0.012) and 1 year (HR: 1.14; 95% CI: 1.09 to
      1.20; p < 0.001) compared with white patients. CONCLUSIONS: Black, Hispanic, and
      Asian patients had a lower mortality risk after a hospitalization for HFpEF
      compared with white patients; black patients had higher readmission rates. These
      differences in mortality and readmission risk according to race/ethnicity
      persisted after adjusting for patient characteristics, SES, and hospital factors.

PMID- 28501530
TI  - Adsorption of plasma proteins onto PEGylated single-walled carbon nanotubes: The
      effects of protein shape, PEG size and grafting density.
AB  - Single-walled carbon nanotubes (SWCNTs) covalently functionalized or
      noncovalently coated with polyethylene glycol (PEG) of different sizes (Mw=2000
      and 5000) and grafting densities (5-16 PEGs per SWCNT) are simulated with human
      fibrinogen (HFG) and serum albumin (HSA). Proteins migrate toward the SWCNT, but
      their adsorption extents differ. The extent of the HFG-SWCNT binding decreases
      with increasing PEG size and grafting density because PEGs more completely cover
      SWCNTs and thus block hydrophobic interactions between HFGs and SWCNTs, which
      occurs on PEG-functionalized SWCNTs but not on PEG-coated ones. In particular,
      the HFG-SWCNT binding significantly decreases in the transition region of PEG
      conformation from mushroom to brush, where PEGs extend like brushes as described
      in the Alexander-de Gennes theory. While the HFG adsorption is modulated by PEG
      conformation, the HSA adsorption is much weaker and less influenced by PEG,
      because spherical HSAs can bind to the restricted area of the SWCNT and thus
      cannot bind to the SWCNT as tightly as do linear HFGs. These findings agree with
      experiments showing less adsorption of proteins on the SWCNT functionalized with
      larger and more PEGs, and support experimental suggestions regarding the
      dependence of protein adsorption on protein shape and the mushroom-brush
      transition of PEG conformation.

PMID- 28501531
TI  - Symmetry in normal modes and its strong dependence on symmetry in structure.
AB  - In this work, we look at the symmetry of normal modes in symmetric structures,
      particularly structures with cyclic symmetry. We show that normal modes of
      symmetric structures have different levels of symmetry, or symmetricity. One
      novel theoretical result of this work is that, for a ring structure with m
      subunits, the symmetricity of the normal modes falls into m groups of equal size,
      with normal modes in each group having the same symmetricity. The normal modes in
      each group can be computed separately, using a much smaller amount of memory and
      time (up to m3 less). Lastly, we show that symmetry in normal modes depends
      strongly on symmetry in structure. This work suggests a deeper reason for the
      existence of symmetric complexes: that they may be formed not only for structural
      purpose, but likely also for a dynamical reason, that certain structural symmetry
      is needed to obtain certain symmetric motions that are functionally critical.

PMID- 28501532
TI  - Targeted inhibition of Klotho binding to fibroblast growth factor 23 prevents
      hypophosphetemia.
AB  - Klotho is a transmembrane protein which plays significant role in the
      pathogenesis of phosphate ion (Pi)-related disorders. Pi accumulation in human
      kidney tissues results in the major metabolic disorders due to malfunctioning of
      Klotho-FGFR1-FGF23 trimeric complex. The potential role of Klotho in Pi
      metabolism was elaborated through modeling and interaction analysis of glycosyl
      hydrolase (GS1 and GS2) domains with Fibroblast growth factor 23 (FGF23). In
      order to inhibit the association of Klotho and FGF23, binding patterns of three
      reported hits (N-(2-chlorophenyl)-1H-indole-3-carboxamide, N-[2-(1-cyclohexen-1
      yl)ethyl]-6,7,8,9-tetrahydropyrido[1,2-e]purin-4-amine and 2-(1-propyl)amino-11
      chlorothiazolo[5,4-a]acridine) were evaluated through molecular docking analysis.
      These inhibitors effectively targeted both GS1 and GS2 domains of Klotho at the
      similar sites required for FGF23 binding. To further characterize the comparative
      binding profile of these compounds, molecular dynamics simulation assays were
      performed. Taken together, current study emphasizes that Klotho may be
      anticipated as a target molecule in familial hypophosphatemic rickets and
      mentioned compounds may prove to be effective therapeutic targets against
      hypophosphetemia induced disorders.

PMID- 28501528
TI  - BCKDK of BCAA Catabolism Cross-talking With the MAPK Pathway Promotes
      Tumorigenesis of Colorectal Cancer.
AB  - Branched-chain amino acids catabolism plays an important role in human cancers.
      Colorectal cancer is the third most commonly diagnosed cancer in males and the
      second in females, and the new global incidence is over 1.2 million cases. The
      branched-chain alpha-keto acid dehydrogenase kinase (BCKDK) is a rate-limiting
      enzyme in branched-chain amino acids catabolism, which plays an important role in
      many serious human diseases. Here we investigated that abnormal branched-chain
      amino acids catabolism in colorectal cancer is a result of the disease process,
      with no role in disease initiation; BCKDK is widely expressed in colorectal
      cancer patients, and those patients that express higher levels of BCKDK have
      shorter survival times than those with lower levels; BCKDK promotes cell
      transformation or colorectal cancer ex vivo or in vivo. Mechanistically, BCKDK
      promotes colorectal cancer by enhancing the MAPK signaling pathway through direct
      MEK phosphorylation, rather than by branched-chain amino acids catabolism. And
      the process above could be inhibited by a BCKDK inhibitor, phenyl butyrate.

PMID- 28501534
TI  - Glomus Tumor of the Stomach-A Tumor That Needs to Be Differentiated From
      Gastrointestinal Stromal Tumor.

PMID- 28501533
TI  - Promising Modalities to Identify and Monitor Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is an allergen-mediated condition characterized by
      symptoms of esophageal dysfunction and histologic evidence of intense
      eosinophilic inflammation involving the esophagus in the absence of overlapping
      conditions such as gastroesophageal reflux disease. Since the initial description
      as a distinct entity approximately 2 decades ago, there has been a remarkable
      increase in the recognition of this clinicopathologic entity. The current
      approach to diagnose and monitor EoE requires repeated
      esophagogastroduodenoscopies, with associated sedation/anesthesia, to visualize
      mucosal abnormalities, and to obtain multiple biopsy specimens for histologic
      assessment and to evaluate treatment response. Frequent
      esophagogastroduodenoscopies with multiple biopsies can increase the risk of
      procedural complications, place significant financial burden on families, and
      escalate health care costs. In addition, this burdensome approach may contribute
      toward delayed diagnosis and suboptimal monitoring, thereby increasing the
      likelihood of complications such as esophageal narrowing and stricture formation,
      which may require escalation of care including endoscopic interventions. Clinical
      progression and complications associated with EoE can be attenuated through early
      identification and optimal management. Therefore, developing reliable, safe, less
      cumbersome, and cost-effective modalities for early diagnosis and effective
      monitoring of EoE is an area of active research. These efforts have been
      substantially supported by the development of new biomaterials, analytic
      methodologies, and the application of novel concepts. Herein, we summarize
      modalities that have shown promise to advance the diagnosis and monitoring of EoE
      and could improve the care of affected individuals and advance the field.

PMID- 28501535
TI  - High Negative Predictive Value, Low Prevalence, and Spectrum Effect: Caution in
      the Interpretation.

PMID- 28501536
TI  - Multicenter External Validation of Risk Stratification Criteria for Patients With
      Variceal Bleeding.
AB  - BACKGROUND & AIMS: Early placement of a transjugular intrahepatic portosystemic
      shunts (TIPS) is considered the treatment of choice for patients with acute
      variceal bleeding (AVB) and cirrhosis who have a high risk of death (Child-Pugh
      class B with active bleeding at endoscopy or Child-Pugh class C). It has been
      proposed that patients of Child-Pugh class B, even with active bleeding, should
      not be considered high risk. Alternative criteria have been proposed for
      identification of high-risk patients, such as Child-Pugh class C with plasma
      level of creatinine of 1 mg/dL or more (ChildC-C1) and a model for end-stage
      liver disease (MELD) score of 19 or more. We analyzed outcomes of a large cohort
      of patients with AVB who received the standard of care at different centers to
      validate these systems of risk stratification. METHODS: We performed an
      observational study of 915 patients with liver cirrhosis and AVB who received
      standard treatment (drugs, antibiotics, and endoscopic ligation, with TIPS as the
      rescue treatment), over different time periods between 2006 and 2014 in Canada
      and Europe. All patients were followed until day 42 (week 6) after index AVB or
      death. Child-Pugh and MELD scores were calculated at time of hospital admission.
      The primary outcome was mortality 6 weeks after index AVB among patients who met
      the early TIPS criteria (Child-Pugh class B with active bleeding at endoscopy or
      Child-Pugh class C), MELD19 criteria (patients with MELD scores of 19 or more),
      and ChildC-C1 criteria. RESULTS: Among 915 patients with AVB, 18% died within 6
      weeks. Among the 523 patients who met the early TIPS criteria, 17% died within 6
      weeks. All 3 rules discriminated patients at high risk of death from those with
      low risk: 28.3% of the patients classified as high risk by the early TIPS
      criteria died whereas only 7.0% of patients classified as low risk died; 46.0% of
      patients classified as high risk by the MELD19 criteria died vs 8.1% of patients
      classified as low risk; 51.9% of patients classified as high risk by the ChildC
      C1 criteria died compared with 10.9% of patients classified as low risk.
      Mortality was significantly lower among patients with Child-Pugh class B (11.7%)
      than with Child-Pugh class C (35.6%) (P <= .001). Mortality was similar between
      patients with Child-Pugh class B cirrhosis with or without active bleeding
      (11.7%). Patients with Child-Pugh class A cirrhosis or MELD scores of 11 or less
      had low mortality (2%-4%), patients with Child-Pugh class B cirrhosis or MELD
      scores of 12 to 18 had intermediate mortality (10%-12%), and patients with Child
      Pugh class C cirrhosis or MELD scores of 19 or more had high mortality (22%-46%).
      CONCLUSIONS: Patients with Child-Pugh class B cirrhosis and AVB who receive
      standard therapy, regardless of the presence of active bleeding, have 3-fold
      lower mortality than patients with Child-Pugh C cirrhosis and might not need
      TIPS. Patients with Child-Pugh class C and/or MELD scores of 19 or more should be
      considered at high risk of death. These findings might help refine criteria for
      early TIPS.

PMID- 28501537
TI  - Effects of Exercise on Liver Fat and Metabolism in Alcohol Drinkers.
AB  - BACKGROUND & AIMS: Exercise is an important component of obesity-associated
      disorders and has been shown to reduce markers of nonalcoholic fatty liver
      disease (NAFLD). However, little is known about how these effects are influenced
      by alcohol intake. The authors performed a randomized controlled trial to
      investigate the effects of exercise on hepatic triglyceride content (HTGC) and
      metabolism in overweight or obese patients who consume alcohol. METHODS: The
      authors performed a prospective study of 27 patients (mean 54 +/- 11 years of
      age, body mass index [BMI] 31 +/- 4 kg/m2) with >5% HTGC in the United Kingdom,
      consuming alcohol (mean 221 +/- 75 g/week). Anthropometry, body composition,
      HTGC, and abdominal fat were measured using plethysmography and magnetic
      resonance imaging. Subjects were assigned to groups that exercised (3 times/week
      on nonconsecutive days) for 12 weeks (n = 14) or continued standard care (control
      group, n = 13), maintaining baseline weight and alcohol consumption. The exercise
      program consisted of aerobic exercise (static cycling) and a circuit of
      resistance exercise (free weights and machines). Patients were examined at
      baseline and at 12 weeks; data collected on HTGC, body composition, metabolic
      control, circulating inflammatory, and fibrosis markers were assessed at baseline
      and at 12 weeks. Between-group differences were evaluated using an unpaired t
      test and within-group differences using a paired t test. The primary outcomes for
      this study were changes in HTGC between baseline and 12 weeks. RESULTS: After 12
      weeks, there was no significant difference between the exercise and control
      groups in HTGC (reduction of 0.1% +/- 2.1% in exercisers vs increase of 0.5 +/-
      2.1% in control group; P > .05). At week 12, the exercise group had significant
      reductions in subcutaneous fat (loss of 23 +/- 28 cm2 in the exercisers vs
      increase of 12 +/- 19 cm2 in the control group; P < .01), and whole body fat
      (loss of 2.1 +/- 1.1 kg in the exercisers vs increase of 0.2 +/- 2.1 kg; P <
      .01). The exercise group also had a significantly greater increase in lean body
      mass (increase of 1.9 +/- 1.4 kg for the exercisers vs increase of 0.7 +/- 1.5 kg
      for the control group; P < .01) and a significantly greater reduction in level of
      cytokeratin 18 (reduction of 49 +/- 82 U/L in exercisers vs increase of 17 +/- 38
      U/L in control group; P < .05). There were no differences between groups in
      changes in metabolic factors or markers of inflammation. CONCLUSIONS: In a
      randomized controlled trial of obese individuals who consume alcohol, exercise
      significantly improved body composition and reduced hepatocyte apoptosis
      (cytokeratin 18), but did not reduce HTGC. This finding could indicate that
      alcohol consumption reduces the effects of exercise on NAFLD observed in previous
      studies. Clinical care teams should look to use exercise as part of the
      management strategy for people consuming alcohol, but optimal benefit may be as
      an adjunct to alcohol reduction and weight management strategies. (ISRCTN.com,
      Number: ISRCTN90597099).

PMID- 28501538
TI  - Biopsy Specimens From Allograft Liver Contain Histologic Features of Hepatitis C
      Virus Infection After Virus Eradication.
AB  - BACKGROUND & AIMS: Most patients, even those who have received a liver
      transplant, achieve a sustained virologic response (SVR) to therapy for hepatitis
      C virus (HCV) infection. Little is known about the histologic features of liver
      biopsy specimens collected after SVR, particularly in patients who have received
      a liver transplant. We aimed to better characterize the histologic features of
      allograft liver biopsy specimens from patients who achieved SVR to anti-HCV
      therapy after liver transplantation. METHODS: We performed a retrospective
      analysis of 170 allograft liver biopsy specimens from 36 patients who received a
      liver transplant for chronic HCV infection, had recurrent HCV infection after
      transplantation, and subsequently achieved SVR (collected from 1999 through 2015
      at 4 medical centers). SVR was defined as an undetectable serum HCV RNA level 24
      weeks after completion of HCV treatment. A total of 65 biopsy specimens were post
      SVR (at least 1 post-SVR from each patient; some biopsy specimens were collected
      at later time points from a subset of patients). We performed polymerase chain
      reaction analysis for HCV RNA on a subset of the biopsy specimens (28 collected
      before SVR and 32 after SVR). RESULTS: Of the 65 post-SVR biopsy specimens, 45
      (69%) had histologic features of active HCV infection. Of the initial post-SVR
      biopsy specimens collected from each of the 36 patients, 32 (89%) showed these
      changes. For patients with more than 1 post-SVR biopsy specimen, 6 (46%) had no
      change in fibrosis between biopsies, and fibrosis worsened for 3 patients (23%)
      based on their most recent biopsy. The HCV RNA level was undetectable in 31 of
      the 32 biopsy specimens analyzed by polymerase chain reaction. CONCLUSIONS: In a
      retrospective analysis of allograft liver biopsy specimens from patients who
      achieved SVR after a liver transplant for chronic HCV infection, histologic
      changes associated with active HCV were present in 69% and fibrosis continued to
      progress in 23%, despite the lack of detection of HCV RNA. Pathologists should be
      aware of patients' SVR status when analyzing liver biopsy specimens to avoid
      diagnoses of chronic HCV-associated hepatitis. Because of the persistent
      inflammatory activity and fibrosis after SVR, clinicians should continue to
      monitor patients carefully after SVR to anti-HCV therapy.

PMID- 28501540
TI  - FT-IR spectroscopic study of amyloid protein formation and aortic valve
      calcification.

PMID- 28501539
TI  - Spatiotemporal oscillatory dynamics of visual selective attention during a
      flanker task.
AB  - The flanker task is a test of visual selective attention that has been widely
      used to probe error monitoring, response conflict, and related constructs.
      However, to date, few studies have focused on the selective attention component
      of this task and imaged the underlying oscillatory dynamics serving task
      performance. In this study, 21 healthy adults successfully completed an arrow
      based version of the Eriksen flanker task during magnetoencephalography (MEG).
      All MEG data were pre-processed and transformed into the time-frequency domain.
      Significant oscillatory brain responses were imaged using a beamforming approach,
      and voxel time series were extracted from the peak responses to identify the
      temporal dynamics. Across both congruent and incongruent flanker conditions, our
      results indicated robust decreases in alpha (9-12Hz) activity in medial and
      lateral occipital regions, bilateral parietal cortices, and cerebellar areas
      during task performance. In parallel, increases in theta (3-7Hz) oscillatory
      activity were detected in dorsal and ventral frontal regions, and the anterior
      cingulate. As per conditional effects, stronger alpha responses (i.e., greater
      desynchronization) were observed in parietal, occipital, and cerebellar cortices
      during incongruent relative to congruent trials, whereas the opposite pattern
      emerged for theta responses (i.e., synchronization) in the anterior cingulate,
      left dorsolateral prefrontal, and ventral prefrontal cortices. Interestingly, the
      peak latency of theta responses in these latter brain regions was significantly
      correlated with reaction time, and may partially explain the amplitude difference
      observed between congruent and incongruent trials. Lastly, whole-brain
      exploratory analyses implicated the frontal eye fields, right temporoparietal
      junction, and premotor cortices. These findings suggest that regions of both the
      dorsal and ventral attention networks contribute to visual selective attention
      processes during incongruent trials, and that such differential processes are
      transient and fully completed shortly after the behavioral response in most
      trials.

PMID- 28501541
TI  - Characteristics Associated with Treatment Response and Satisfaction in Women
      Undergoing OnabotulinumtoxinA and Sacral Neuromodulation for Refractory Urgency
      Urinary Incontinence.
AB  - PURPOSE: We sought to identify clinical and demographic characteristics
      associated with treatment response and satisfaction in women undergoing
      onabotulinumtoxinA and sacral neuromodulation therapies. MATERIALS AND METHODS:
      We analyzed data from the ROSETTA (Refractory Overactive Bladder: Sacral
      NEuromodulation versus BoTulinum Toxin Assessment) trial. Baseline participant
      characteristics and clinical variables were associated with 2 definitions of
      treatment response, including 1) a reduction in mean daily urgency incontinence
      episodes during 6 months and 2) a 50% or greater decrease in urgency incontinence
      episodes across 6 months. The OAB-S (Overactive Bladder-Satisfaction)
      questionnaire was used to assess satisfaction. RESULTS: A greater reduction in
      mean daily urgency incontinence episodes was associated with higher HUI-3 (Health
      Utility Index-3) scores in the onabotulinumtoxinA group and higher baseline
      incontinence episodes (each p <0.001) in the 2 groups. Increased age was
      associated with a lesser decrease in incontinence episodes in the 2 groups (p
      <0.001). Increasing body mass index (adjusted OR 0.82/5 points, 95% CI 0.70-0.96)
      was associated with reduced achievement of a 50% or greater decrease in
      incontinence episodes after each treatment. Greater age (adjusted OR 0.44/10
      years, 95% CI 0.30-0.65) and a higher functional comorbidity index (adjusted OR
      0.84/1 point, 95% CI 0.71-0.99) were associated with reduced achievement of a 50%
      or greater decrease in urgency incontinence episodes in the onabotulinumtoxinA
      group only (p <0.001 and 0.041, respectively). In the onabotulinumtoxinA group
      increased satisfaction was noted with higher HUI-3 score (p = 0.002) but there
      was less satisfaction with higher age (p = 0.001). CONCLUSIONS: Older women with
      multiple comorbidities, and decreased functional and health related quality of
      life had decreased treatment response and satisfaction with onabotulinumtoxinA
      compared to sacral neuromodulation for refractory urgency incontinence.

PMID- 28501542
TI  - Metabolite profile of koji amazake and its lactic acid fermentation product by
      Lactobacillus sakei UONUMA.
AB  - The koji amazake is a traditional sweet Japanese beverage. It has been consumed
      for over a thousand years in Japan; nonetheless, little is yet known of the
      ingredients in koji amazake. Therefore, this study aimed to analyze the
      metabolites of koji amazake using a metabolomics approach. Additionally, we
      reformed the flavor of koji amazake by lactic acid fermentation (LAF-amazake)
      using Lactobacillus sakei UONUMA, which was isolated from snow caverns. The
      purpose of this article is to identify the ingredients in these beverages. In LAF
      amazake and koji amazake, sugars, amino acids, organic acids, and vitamin B
      complex were determined in the two beverages, and over 300 compounds were
      detected in total. Thirteen saccharides were identified including two unknown
      trisaccharides, and there were no differences in these between the two beverages.
      In LAF-amazake, lactic acid, vitamin B2 (riboflavin), B3 (nicotinic acid and
      nicotinamide), and B6 (pyridoxine) were significantly increased as compared to
      koji amazake, whereas malate and glutamine decreased. These results suggested
      that LAF, malolactic fermentation, and glutamine deamidation occurred
      simultaneously in LAF-amazake. L. sakei UONUMA strains produced these vitamins.
      Moreover, it was surprising that acetylcholine, a well-known neurotransmitter,
      was newly generated in LAF-amazake. Here, we have succeeded in reforming the
      flavor of koji amazake and obtained these metabolic data on the two beverages.
      The present study could provide useful basic information for promoting functional
      analyses of koji amazake and LAF-amazake for human health.

PMID- 28501543
TI  - Allogeneic Hematopoietic Stem Cell Transplantation for Adolescents and Young
      Adults with Acute Myeloid Leukemia.
AB  - Few reports have focused on adolescent and young adult (AYA) patients with acute
      myeloid leukemia (AML) treated with hematopoietic stem cell transplantation
      (HSCT). We performed a retrospective analysis based on data obtained from a
      Japanese nationwide registration database to compare HSCT outcomes in AYA
      patients with AML with those in children with AML. An analysis of the 2973
      patients with de novo AML who received allogeneic HSCT from 1990 to 2013 showed
      inferior 5-year overall survival (OS) (54% versus 58%, P <.01) and increased
      treatment-related mortality (TRM) (16% versus 13%, P = .02) in AYA patients.
      Multivariate analysis for both OS and TRM showed a significant negative impact on
      AYAs. However, the negative impact of older age lost its significance in an
      additional analysis focusing on 1407 recent transplant recipients with high
      resolution HLA typing (2000 to 2013). Finally, we analyzed the impact of
      transplantation center type on HSCT outcomes in 317 adolescent patients (15 to 18
      years old) and found no difference in outcomes between patients treated at a
      pediatric or an adult hospital. Higher age was a strong predictive factor for
      inferior OS resulting from increased TRM, which can be eliminated with better
      donor selection using high-resolution HLA typing.

PMID- 28501544
TI  - The DNA methylation status alteration of two steroidogenic genes in gonads of
      rare minnow after bisphenol A exposure.
AB  - Both cytochrome P450c17 (CYP17A1) and P-450 side chain cleavage (CYP11A1) play
      important roles in steroid biosynthesis. According to our previous studies,
      bisphenol A (BPA) could regulate the mRNA expression of cyp17a1 and cyp11a1 in
      rare minnow Gobiocypris rarus. However, the potential mechanism of the regulation
      is barely understood. In the present study, aiming to explore how BPA affects the
      mRNA expression of cyp17a1 and cyp11a1 in testes and ovaries of G. rarus, we
      firstly cloned 340-bp fragment of 5' flanking region of cyp11a1 and then detected
      the methylation level of CpG loci involved in 5' flanking of cyp11a1 and cyp17a1
      and their mRNA expression levels. Results showed that exposure to BPA
      significantly increased serum estradiol (E2) and 11-ketotesterone (11-KT)
      concentrations. Ovarian mRNA expression of cyp17a1 and cyp11a1 were significantly
      decreased after BPA exposure 7- for and 14-days. However, transcriptions of
      testicular cyp17a1 and cyp11a1 were significantly increased and decreased
      respectively after BPA treatment for 14days. The DNA methylation levels of
      cyp17a1 were decreased in ovaries on day 7 and increased in ovaries and decreased
      in testes respectively on day 14. The methylation levels of cyp11a1 were
      increased in ovaries on day 7 and both ovaries and testes on day 14. There were a
      significant correlation between DNA methylation at specific CpG loci and cyp17a1
      and cyp11a1 genes transcription levels. In conclusion, the CpG loci methylation
      in 5' flanking region appears to involve in the regulation of mRNA expression of
      cyp17a1 and cyp11a1 mediated by BPA.

PMID- 28501545
TI  - Betamethasone causes intergenerational reproductive impairment in male rats.
AB  - Prenatal betamethasone (BM) exposure in rats negatively impacts sperm quality and
      male fertility. Studies have shown that BM can cause multi-generational effects
      on the pituitary-adrenal-axis of rats. The objective of this study was to assess
      the reproductive development and fertility of male rats (F2) whose fathers (F1)
      were exposed to BM (0.1mg/kg) on gestational days 12, 13, 18 and 19. In F2 rats,
      there was a significant reduction in body weights of the BM-treated group at PND
      1 as well as delayed onset of puberty, and decreases in FSH levels, Leydig cell
      volume, sperm number and motility, seminal vesicle contractility and ejaculated
      volume. Furthermore, increased serum LH levels, sperm DNA damage and abnormal
      morphology were observed, resulting in reduced fertility. In conclusion, prenatal
      BM-treatment leads to intergenerational long-term reproductive impairment in male
      rats, raising concern regarding the widespread use of BM in preterm births.

PMID- 28501546
TI  - Diagnosis of primary ciliary dyskinesia: When and how?
AB  - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare congenital disorder
      involving permanent ubiquitous structural and/or functional ciliary
      abnormalities. METHODS: A single-center retrospective study included 56 cases of
      PCD (respiratory form) out of a cohort of 280 patients with suspected PCD. The
      main features of history-taking and clinical examination were analyzed, to
      formulate a pragmatic diagnostic procedure, easy to implement in clinical
      practice. RESULTS: Chronic respiratory tract infectious symptoms are sensitive
      but non-specific for the diagnosis of PCD. Nasal brushing for phase-contrast
      microscopy study of ciliary morphology and activity proved to be a fast, easy,
      non-invasive, cost-effective and age-independent diagnostic method. In doubtful
      cases, depending on local availability, further tests are indicated: nasal nitric
      oxide level, electronic microscopy, genetic study and cell culture. CONCLUSIONS:
      In suspected PCD, there being no gold standard method of screening and early
      diagnosis, nasal brushing with ciliary study is contributive, alongside numerous
      other complementary tests, on condition that the clinician is experienced and
      results are interpreted in the light of clinical examination and history-taking.

PMID- 28501547
TI  - Drawn together: When motor representations ground joint actions.
AB  - What enables individuals to act together? Recent discoveries suggest that a
      variety of mechanisms are involved. But something fundamental is yet to be
      investigated. In joint action, agents represent a collective goal, or so it is
      often assumed. But how, if at all, are collective goals represented in joint
      action and how do such representations impact performance? To investigate this
      question we adapted a bimanual paradigm, the circle-line drawing paradigm, to
      contrast two agents acting in parallel with two agents performing a joint action.
      Participants were required to draw lines or circles while observing circles or
      lines being drawn. The findings indicate that interpersonal motor coupling may
      occur in joint but not parallel action. This suggests that participants in joint
      actions can represent collective goals motorically.

PMID- 28501549
TI  - The effect of phasic auditory alerting on visual perception.
AB  - Phasic alertness refers to a short-lived change in the preparatory state of the
      cognitive system following an alerting signal. In the present study, we examined
      the effect of phasic auditory alerting on distinct perceptual processes,
      unconfounded by motor components. We combined an alerting/no-alerting design with
      a pure accuracy-based single-letter recognition task. Computational modeling
      based on Bundesen's Theory of Visual Attention was used to examine the effect of
      phasic alertness on visual processing speed and threshold of conscious
      perception. Results show that phasic auditory alertness affects visual perception
      by increasing the visual processing speed and lowering the threshold of conscious
      perception (Experiment 1). By manipulating the intensity of the alerting cue, we
      further observed a positive relationship between alerting intensity and
      processing speed, which was not seen for the threshold of conscious perception
      (Experiment 2). This was replicated in a third experiment, in which pupil size
      was measured as a physiological marker of alertness. Results revealed that the
      increase in processing speed was accompanied by an increase in pupil size,
      substantiating the link between alertness and processing speed (Experiment 3).
      The implications of these results are discussed in relation to a newly developed
      mathematical model of the relationship between levels of alertness and the speed
      with which humans process visual information.

PMID- 28501548
TI  - Facilitation and interference in naming: A consequence of the same learning
      process?
AB  - Our success with naming depends on what we have named previously, a phenomenon
      thought to reflect learning processes. Repeatedly producing the same name
      facilitates language production (i.e., repetition priming), whereas producing
      semantically related names hinders subsequent performance (i.e., semantic
      interference). Semantic interference is found whether naming categorically
      related items once (continuous naming) or multiple times (blocked cyclic naming).
      A computational model suggests that the same learning mechanism responsible for
      facilitation in repetition creates semantic interference in categorical naming
      (Oppenheim, Dell, & Schwartz, 2010). Accordingly, we tested the predictions that
      variability in semantic interference is correlated across categorical naming
      tasks and is caused by learning, as measured by two repetition priming tasks
      (picture-picture repetition priming, Exp. 1; definition-picture repetition
      priming, Exp. 2, e.g., Wheeldon & Monsell, 1992). In Experiment 1 (77 subjects)
      semantic interference and repetition priming effects were robust, but the results
      revealed no relationship between semantic interference effects across contexts.
      Critically, learning (picture-picture repetition priming) did not predict
      semantic interference effects in either task. We replicated these results in
      Experiment 2 (81 subjects), finding no relationship between semantic interference
      effects across tasks or between semantic interference effects and learning
      (definition-picture repetition priming). We conclude that the changes underlying
      facilitatory and interfering effects inherent to lexical access are the result of
      distinct learning processes where multiple mechanisms contribute to semantic
      interference in naming.

PMID- 28501550
TI  - Type 2 diabetes alters hippocampal gamma oscillations: A potential mechanism
      behind impaired cognition.
AB  - Type 2 diabetes (T2D) has been associated with cognitive decline, dementia and
      Alzheimer's disease (AD). Remarkably, the pathophysiological mechanisms behind
      this are still mostly unknown. Cognition and memory formation are associated with
      gamma oscillations in hippocampal neuronal networks and fast-spiking, parvalbumin
      expressing interneurons (PV+ IN) play a key role in these processes.

PMID- 28501551
TI  - Contribution of stress and sex hormones to memory encoding.
AB  - Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC)
      affect sex hormone levels, stress responses, and memory processes critically
      involved in the pathogenesis of mental disorders. To characterize the interaction
      of sex and stress hormones on memory encoding, 30 men, 30 women in the early
      follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU),
      and 30 OC women were exposed to either a stress (socially evaluated cold-pressor
      test) or a control condition prior to memory encoding and immediate recall of
      neutral, positive, and negative words. On the next day, delayed free and cued
      recall was tested. Sex hormone levels verified distinct estradiol, progesterone,
      and testosterone levels between groups. Stress increased blood pressure, cortisol
      concentrations, and ratings of stress appraisal in all four groups as well as
      cued recall performance of negative words in men. Stress exposure in OC women led
      to a blunted cortisol response and rather enhanced cued recall of neutral words.
      Thus, pre-encoding stress facilitated emotional cued recall performance in men
      only, but not women with different sex hormone statuses pointing to the pivotal
      role of circulating sex hormones in modulation of learning and memory processes.

PMID- 28501552
TI  - Taking turns across channels: Conversation-analytic tools in animal
      communication.
AB  - In the quest to bridge the gulf between the fields of linguistics and animal
      communication, interest has recently been drawn to turn-taking behavior in social
      interaction. Vocal turn-taking is the core form of language usage in humans, and
      has been examined in numerous species of birds and primates. Recent studies on
      great apes have shown that they engage in a bodily form, gestural turn-taking, to
      achieve mutual communicative goals. However, most studies on turn-taking
      neglected the fact that signals are prevalently perceived and produced in a
      multimodal format. Here, I propose that research on animal communication may
      benefit a more holistic and dynamic approach: studying turn-taking using a
      multimodal, conservation-analytic framework. I will discuss recent comparative
      research that implemented this approach via a specific set of parameters. In sum,
      I argue that a conversation-analytic framework might help substantially to
      pinpoint the ways in which crucial components of language are embodied in the
      'human interaction engine'.

PMID- 28501553
TI  - Progressive cortical reorganisation: A framework for investigating structural
      changes in schizophrenia.
AB  - One of the few well-replicated features of schizophrenia is the demonstration of
      neuroanatomical abnormalities affecting cortical and subcortical grey matter
      (GM). Evidence to date suggests that the greatest reduction in GM occurs in the
      immediate post-onset phase. The predominant view to date is that the accelerated
      grey matter (GM) loss represents an adverse process (degenerative or
      developmental deficit) contributing to the unfavourable course of schizophrenia.
      This prevailing emphasis on decompensation often overlooks the fact that human
      brain has an inherent capacity to remodel itself in response to insults that
      affect its function. In the wake of emerging insights into both micro- and macro
      scale brain connectivity, a substantial amount of the longitudinal structural
      changes seen in patients with schizophrenia could result from a distributed,
      nevertheless inefficient, cortical reorganization response. Quantifying cortical
      reorganization in the early stages of illness can enable prospective grading of
      the underlying pathophysiological process in schizophrenia.

PMID- 28501554
TI  - Molecular typing of Clostridium difficile isolates cultured from patient stool
      samples and gastroenterological medical devices in a single Iranian hospital.
AB  - This study aimed to characterize Clostridium difficile isolates cultured from
      stool samples of patients with C. difficile infection (CDI) and swabs from a
      medical environment in a gastroenterology center in Tehran, Iran. A total of 158
      samples (105 stool samples from hospitalized patients and 53 swabs from medical
      devices and the environment) were collected from January 2011 to August 2011 and
      investigated for the presence of C. difficile by direct anaerobic culture on a
      selective media for C. difficile. C. difficile isolates were further
      characterized by capillary electrophoresis (CE) ribotyping and toxin gene
      multiplex PCR. Of 158 samples, C. difficile was cultured in 19 of 105 stool
      samples (18%) and in 4 of 53 swabs (7.5%). C. difficile PCR ribotype (RT) 126 was
      the most common RT in the study (21.7%). Further RTs were: 001, 003, 014, 017,
      029, 039, 081, 103 and 150. RTs 126, 001, 150 were cultured from both the stool
      samples and swabs of medical devices and the hospital environment which suggest a
      possible route of transmission.

PMID- 28501555
TI  - Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2-Amplified
      Gastric Cancer Patient-Derived Cell Model.
AB  - BACKGROUND: FGFR2 amplification is associated with aggressive gastric cancer
      (GC), and targeted drugs have been developed for treatment of GC. We evaluated
      the antitumor activity of an FGFR inhibitor in FGFR2-amplified GC patients with
      peritoneal carcinomatosis. METHODS: Two GC patients with FGFR2 amplification
      confirmed by fluorescence in situ hybridization showed peritoneal seeding and
      malignant ascites. We used the patient-derived xenograft model; patient-derived
      cells (PDCs) from malignant ascites were used to assess FGFR2 expression and its
      downstream pathway using immunofluorescence analysis and immunoblot assay in
      vitro. Apoptosis and cell cycle arrest after treatment of FGFR inhibitor were
      analyzed by Annexin V-FITC assay and cell cycle analysis. RESULTS: FGFR2
      amplification was verified in both PDC lines. AZD4547 as an FGFR inhibitor
      decreased proliferation of PDCs, and the IC50 value was estimated to be 250 nM in
      PDC#1 and 210 nM in PDC#2. FGFR inhibitor also significantly decreased levels of
      phosphorylated FGFR2 and downstream signaling molecules in FGFR2-amplified PDC
      lines. In cell cycle analysis, apoptosis was significantly increased in AZD4547
      treated cells compared with nontreated cells. The proportion of cells in the sub
      G1 stage was significantly higher in AZD4547-treated PDCs than in control cells.
      CONCLUSION: Our findings suggest that FGFR2 amplification is a relevant
      therapeutic target in GC with peritoneal carcinomatosis.

PMID- 28501557
TI  - The positive cognitive impact of aerobic fitness is associated with peripheral
      inflammatory and brain-derived neurotrophic biomarkers in young adults.
AB  - There is ample evidence for supporting the positive impact of aerobic fitness on
      cognitive function, but little is known about the physiological mechanisms. The
      objective of this study was to investigate whether the positive cognitive impact
      of aerobic fitness is associated with inflammatory and neurotrophic peripheral
      biomarkers in young adults aged 18 to 29years (n=87). For the objective
      assessment of aerobic fitness, we measured maximal oxygen uptake (VO2max) as a
      parametric measure of cardiorespiratory capacity. We demonstrated that young
      adults with the higher levels of VO2max performed better on computerized
      cognitive tasks assessing sustained attention and working memory. This positive
      VO2max-cognitive performance association existed independently of confounders
      (e.g., years of education, intelligence scores) but was significantly dependent
      on resting peripheral blood levels of inflammatory (C-reactive protein, CRP) and
      neurotrophic (brain-derived neurotrophic factor, BDNF) biomarkers. Statistical
      models showed that CRP was a mediator of the effect of VO2max on working memory.
      Further, BDNF was a moderator of the effect of VO2max on working memory. These
      mediating and moderating effects occurred in individuals with higher levels of
      aerobic fitness. The results suggest that higher aerobic fitness, as measured by
      VO2max, is associated with enhanced cognitive functioning and favorable resting
      peripheral levels of inflammatory and brain-derived neurotrophic biomarkers in
      young adults.

PMID- 28501556
TI  - Behavioral and physiological reactions in dogs to a veterinary examination: Owner
      dog interactions improve canine well-being.
AB  - In order to improve well-being of dogs during veterinary visits, we aimed to
      investigate the effect of human social interactions on behavior and physiology
      during routine examination. Firstly, we assessed the impact of a standardized
      veterinary examination on behavioral and physiological indicators of stress in
      dogs. Secondly, we examined whether the owner's tactile and verbal interactions
      with the dog influenced behavioral and physiological stress-associated
      parameters. A randomized within-subjects crossover design was used to examine
      behavior (n=33), rectal temperature (n=33), heart rate (HR) (n=18), maximal
      ocular surface temperature (max OST) (n=13) and salivary cortisol concentrations
      (n=10) in healthy privately owned pet dogs. The study consisted of two
      experimental conditions: a) "contact" - owner petting and talking to the dog
      during the examination; b) "non-contact" - owner present during the examination
      but not allowed to interact with the dog. Our findings showed that the veterinary
      examinations produced acute stress responses in dogs during both "contact" and
      "non-contact" conditions, with significant increases in lip licking, HR, and max
      OST. A significant decrease in attempts to jump off the examination table
      (p=0.002) was observed during the examination in the "contact" compared to the
      "non-contact" condition. In addition, interactions of owners showed an
      attenuating effect on HR (p=0.018) and max OST (p=0.011) in their dogs. The
      testing order (first vs. second visit) had no impact on behavioral and
      physiological parameters, suggesting that dogs did not habituate or sensitize to
      the examination procedure. Moreover, the duration of the owner-dog interactions
      had no significant impact on the behavioral and physiological responses of their
      dogs. This study demonstrates that owner-dog interactions improve the well-being
      of dogs during a veterinary examination. Future research may assist in further
      understanding the mechanisms associated with reducing stress in dogs in similar
      settings.

PMID- 28501558
TI  - Effects of prolonged exposure to CO2 on behaviour, hormone secretion and
      respiratory muscles in young female rats.
AB  - Atmospheric CO2 concentrations increased significantly over the last century and
      continuing increases are expected to have significant effects on current
      ecosystems. This study evaluated the behavioural and physiological (hormone
      status, muscle structure) effects of prolonged CO2 exposure in young female
      Wistar rats exposed at 700ppm of CO2 during 6h a day for 15days. Prolonged CO2
      exposure, though not continuous, produced significant disturbances in behaviour
      with an increase in drinking, grooming and resting, and a reduction in rearing,
      jumping-play and locomotor activity. Furthermore, CO2 exposure was accompanied by
      increased plasma levels of corticosterone, suggesting that prolonged exposure to
      CO2 was stressful. The muscular structure can also be modified also when
      respiratory working conditions change. The expression of myosin heavy chain was
      significantly affected in the diaphragm and oral respiratory muscles: Masseter
      Superficialis and Anterior Digastric. Modified behaviour and hormonal changes
      both appear to be at the origin of the observed muscular adaptation.

PMID- 28501559
TI  - Fast, accurate and easy-to-teach QT interval assessment: The triplicate
      concatenation method.
AB  - BACKGROUND: The gold standard method for assessing the QTcF (QT corrected for
      heart rate by Fridericia's cube root formula) interval is the "QTcF semiautomated
      triplicate averaging method" (TAM), which consists of measuring three QTcF values
      semiautomatically, for each 10-second sequence of a triplicate electrocardiogram
      set, and averaging them to get a global and unique QTcF value. Thus, TAM is time
      consuming. We have developed a new method, namely the "QTcF semiautomated
      triplicate concatenation method" (TCM), which consists of concatenating the three
      10-second sequences of the triplicate electrocardiogram set as if they were a
      single 30-second electrocardiogram, and measuring QTcF only once for the
      triplicate electrocardiogram set. AIM: To compare the TCM method with the TAM
      method. METHODS: Fifty triplicate electrocardiograms were read twice by an expert
      and a student using both methods (TAM and TCM). We plotted Bland-Altman plots to
      assess agreement between the two methods, and to compare the student and expert
      results. The time needed to read a set of 20 consecutive triplicate
      electrocardiograms was measured. RESULTS: Limits of agreement between TAM and TCM
      ranged from -8.25 to 6.75ms with the expert reader. TCM was twice as fast as TAM
      (17.38 versus 34.28min for 20 consecutive triplicate electrocardiograms). Bland
      Altman plots comparing student and expert results showed limits of agreement
      ranging from -4.34 to 11.75ms for TAM, and -1.2 to 8.0ms for TCM. CONCLUSIONS:
      TAM and TCM show good agreement for QT measurement. TCM is less time consuming
      than TAM. After a learning session, an inexperienced reader can measure the QT
      interval accurately with both methods.

PMID- 28501560
TI  - The immune microenvironment and HPV in anal cancer: Rationale to complement
      chemoradiation with immunotherapy.
AB  - Anal squamous cell carcinomas (ASCC) are increasing in frequency across the
      developed world, and 70-90% of all cases originate from infection with human
      papilloma viruses (HPV). Primary chemoradiotherapy (CRT) is the standard
      treatment for ASCC, but local and/or distant failure still occurs in up to 30% of
      patients. HPV-associated ASCC and tumors with a higher density of tumor
      infiltrating lymphocytes (TIL) carry a better prognosis. Furthermore, HPV can
      render tumors more immunogenic, whereas it correlates with elevated TIL
      densities. This comprehensive review highlights the progress made in
      understanding the immune microenvironment of anal intraepithelial neoplasias and
      ASCC in the context of HPV. Here, we discuss the immunomodulatory potential of
      CRT, the prognostic impact of immune checkpoint markers, and the rationale for
      including immunotherapies to further improve the clinical outcome in patients
      with ASCC.

PMID- 28501561
TI  - The sleeping ugly: Tumour microenvironment's act to make or break the spell of
      dormancy.
AB  - Metastasis is the main cause of death for most cancer patients. It appears clear
      from clinical observations that the majority of cancers, particularly carcinoma
      do not follow a linear model of metastatic progression, where cancer cells shed
      from the primary tumour, disseminate to a distant organ and immediately outgrow
      to form clinical metastasis. Certainly, while cancer spreading is an early event,
      metastasis occurs much later during tumour progression and frequently arises
      several years after primary tumour resection. The time spent by disseminated
      cancer cells (DTCs) in a distant organ before their outgrowth is termed
      metastatic latency. We will examine here the current knowledge of the mechanisms
      allowing metastatic latency and discuss the crucial role of the DTCs' tissue
      microenvironment in this process.

PMID- 28501562
TI  - A 'joint venture' model of recontacting in clinical genomics: challenges for
      responsible implementation.
AB  - Advances in genomics often lead healthcare professionals (HCPs) to learn new
      information, e.g., about reinterpreted variants that could have clinical
      significance for patients seen previously. A question arises of whether HCPs
      should recontact these former patients. We present some findings interrogating
      the views of patients (or parents of patients) with a rare or undiagnosed
      condition about how such recontacting might be organised ethically and
      practically. Forty-one interviews were analysed thematically. Participants
      suggested a 'joint venture' model in which efforts to recontact are shared with
      HCPs. Some proposed an ICT-approach involving an electronic health record that
      automatically alerts them to potentially relevant updates. The need for rigorous
      privacy controls and transparency about who could access their data was
      emphasised. Importantly, these findings highlight that the lack of clarity about
      recontacting is a symptom of a wider problem: the lack of necessary
      infrastructure to pool genomic data responsibly, to aggregate it with other
      health data, and to enable patients/parents to receive updates. We hope that our
      findings will instigate a debate about the way responsibilities for recontacting
      under any joint venture model could be allocated, as well as the limitations and
      normative implications of using ICT as a solution to this intractable problem. As
      a first step to delineating responsibilities in the clinical setting, we suggest
      HCPs should routinely discuss recontacting with patients/parents, including the
      new information that should trigger a HCP to initiate recontact, as part of the
      consent process for genetic testing.

PMID- 28501563
TI  - Kindlin-1 protects cells from oxidative damage through activation of ERK
      signalling.
AB  - Kindlin-1 is a FERM domain containing adaptor protein that is found predominantly
      at cell-extracellular matrix adhesions where it binds to beta-integrin subunits
      and is required for integrin activation. Loss of function mutations in the FERMT1
      gene which encodes Kindlin-1 leads to the development of Kindler Syndrome (KS) an
      autosomal recessive skin disorder characterized by skin blistering,
      photosensitivity, and predisposition to aggressive squamous cell carcinoma (SCC).
      Here we show that loss of Kindlin-1 sensitizes both SCC cells and keratinocytes
      to oxidative stress: Kindlin-1 deficient cells have higher levels of reactive
      oxygen species, decreased viability and increased DNA damage after treatment with
      either hydrogen peroxide (H2O2) or irradiation with UVA. We show that Kindlin-1
      is required to fully activate ERK signalling after oxidative damage, and that
      activation of ERK protects cells from DNA damage following oxidative stress:
      inhibition of ERK activation sensitizes Kindlin-1 expressing cells, but not
      Kindlin-1 deficient cells to oxidative stress. Finally we demonstrate that the
      Kindlin-1 dependent activation of ERK and protection from DNA damage following
      oxidative stress depends on the ability of Kindlin-1 to bind integrins. Thus loss
      of Kindlin-1 leads to an imbalance in the cellular oxidative state, which renders
      Kindlin-1 deficient cells more prone to the effects of ROS generated in response
      to oxidative stress. We propose that Kindlin-1 dependent activation of ERK
      signalling is a key molecular mechanism that renders KS keratinocytes more
      sensitive to oxidative damage and contributes to the increased photosensitivity
      in KS patients.

PMID- 28501564
TI  - Wntless promotes bladder cancer growth and acts synergistically as a molecular
      target in combination with cisplatin.
AB  - PURPOSE: To analyze the contribution of Wnt signaling pathway to bladder cancer
      growth in order to identify suitable target molecules for therapy. MATERIAL AND
      METHODS: Expression of Wnt 2/4/7, LRP5/6, TCF1/2/4, LEF-1, and beta-actin was
      detected by reverse transcription polymerase chain reaction in a panel of 9 and
      for Wntless (WLS) in 17 bladder cancer cell lines. Protein expression of WLS was
      detected in 6 cell lines. Wnt/beta-catenin activity was analyzed using the
      TOPflash/FOPflash luciferase reporter assay. Expression level of beta-catenin,
      WIF1, Dickkopf proteins (DKK), HSulf-2, sFRP4, and WLS was modulated by
      transfecting or infecting cells transiently or stably with respective shRNAs,
      siRNAs, or cDNAs. For protein detection, whole cell lysates were applied to
      sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by
      immunoblots. Effects on cell growth were determined by cell viability assays and
      BrdU/APC incorporation/staining. For 3-dimensional tumor growth, the chicken
      chorioallantoic membrane model was used. Tumor growth was characterized by
      weight. RESULTS: Expression of molecular components and activation of the Wnt
      signaling pathway could be detected in all cell lines. Expression level of beta
      catenin, WIF1, DKK, WLS, and HSulf-2 influenced Wnt activity. Expression of WLS
      was confirmed in 17 cell lines by reverse transcription polymerase chain reaction
      and in 6 cell lines by immunoblotting. WLS positively regulates Wnt signaling,
      cell proliferation, and tumor growth in vitro and in vivo. These effects could be
      reversed by the expression of the Wnt antagonist WIF1 and DKK. Synergistic
      activity of cisplatin and WLS inactivation by genetic silencing could be observed
      on cell viability. CONCLUSION: The Wnt signaling pathway is ubiquitously
      activated in bladder cancer and regulates tumor growth. WLS might be a target
      protein for novel therapies in combination with established chemotherapy
      regimens.

PMID- 28501565
TI  - Prostate zonal anatomy correlates with the detection of prostate cancer on
      multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in
      patients with a solitary PI-RADS v2-scored lesion.
AB  - PURPOSE: To evaluate the positive predictive value (PPV) of the Prostate Imaging
      Reporting and Data System version 2 (PI-RADS v2) assessment method in patients
      with a single suspicious finding on prostate multiparametric magnetic resonance
      imaging (mpMRI). PATIENTS AND METHODS: A total of 176 patients underwent
      MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single
      suspicious finding on mpMRI. The PPV for cancer detection was determined based on
      PI-RADS v2 assessment score and location. RESULTS: Fusion biopsy detected
      prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score
      (GS) >=7 prostate cancer. Targeted biopsy detected 90.5% of all GS>=7 prostate
      cancer. The PPV for GS>=7 detection of PI-RADS v2 category 5 (P5) and category 4
      (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5%
      for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy
      did not miss GS>=7 disease compared with systematic biopsy in P5 lesions in the
      PZ and transition zone. CONCLUSION: The PPV of PI-RADS v2 for prostate cancer in
      patients with a single lesion on mpMRI is dependent on PI-RADS assessment
      category and location. The highest PPV was for a P5 lesion in the PZ.

PMID- 28501567
TI  - Depletion of Jmjd1c impairs adipogenesis in murine 3T3-L1 cells.
AB  - Differentiation of adipocytes is a highly regulated process modulated by multiple
      transcriptional co-activators and co-repressors. JMJD1C belongs to the family of
      jumonji C (jmjC) domain-containing histone demethylases and was originally
      described as a ligand-dependent co-activator of thyroid hormone and androgen
      receptors. Here, we explored the potential role of Jmjd1c in white adipocyte
      differentiation. To investigate the relevance of Jmjd1c in adipogenesis, murine
      3T3-L1 preadipocyte cells with transient knock-down of Jmjd1c (3T3_Jmjd1c) were
      generated. Depletion of Jmjd1c led to the formation of smaller lipid droplets,
      reduced accumulation of triglycerides and maintenance of a more fibroblast-like
      morphology after adipocyte differentiation. Concomitantly, insulin stimulated
      uptake of glucose and fatty acids was significantly reduced in 3T3_Jmjd1c
      adipocytes. In line with these observations we detected lower expression of key
      genes associated with lipid droplet formation (Plin1, Plin4, Cidea) and uptake of
      glucose and fatty acids (Glut4, Fatp1, Fatp4, Aqp7) respectively. Finally, we
      demonstrate that depletion of Jmjd1c interferes with mitotic clonal expansion
      (MCE), increases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at
      promotor regions of adipogenic transcription factors (C/EBPs and PPARgamma) and
      leads to reduced induction of these key regulators. In conclusion, we have
      identified Jmjd1c as a modulator of adipogenesis. Our data suggest that Jmjd1c
      may participate in MCE and the activation of the adipogenic transcription program
      during the induction phase of adipocyte differentiation in 3T3-L1 cells.

PMID- 28501568
TI  - Polytrauma-induced hepatic stress response and the development of liver insulin
      resistance.
AB  - Insulin resistance and metabolic dysfunction are common following injury.
      Polytrauma is defined as combined injuries to more than one body part or organ
      system, and is common in modern warfare, as well as automobile and industrial
      accidents. Polytrauma can include any combination of burn injury, fracture,
      hemorrhage, trauma to the extremities, and blunt or penetrating trauma. Multiple
      minor injuries are often more deleterious than a more severe single injury. To
      investigate the mechanisms of development of insulin resistance following injury,
      we have developed a rat model of polytrauma which combined soft tissue trauma
      with burn injury and penetrating gastrointestinal (GI) trauma. Male Sprague
      Dawley rats were subjected to a laparotomy plus either a 15-18% total body
      surface area scald burn or a single puncture of the cecum (CLP) with a G30
      needle, or the combination of both burn and CLP injuries (polytrauma). We
      examined the effects of polytrauma which increased markers of hepatic endoplasmic
      reticulum (ER) stress, and increased hepatic Trib3 mRNA levels coincident with
      reduced insulin-inducible insulin signaling. Phosphorylation/activation of the
      insulin receptor (IR) and AKT were decreased at 24, but not 6h following
      polytrauma. These results demonstrate a complex, time-dependent development of
      hepatic ER-stress and a diminished response to insulin, which were among the
      pathological sequelae following polytrauma.

PMID- 28501570
TI  - Electrocatalytic properties of N-doped graphite felt in electro-Fenton process
      and degradation mechanism of levofloxacin.
AB  - The degradation of antibiotic levofloxacin was investigated by dimensionally
      stable anode as well as modified cathode using low-cost chemical reagents of
      hydrazine hydrate and ethanol for electro-Fenton in an undivided cell at pH 3.0
      under room temperature. Comparison of unmodified and modified cathode was
      performed. The apparent rate constant of levofloxacin decay was found to be
      0.2883 min-1 for graphite felt-10 with the best performance at 200 mA, which is
      lower than graphite felt at 400 mA. The optimum modified cathode showed a
      significant improvement of complete mineralization of levofloxacin, reaching a
      92% TOC removal at 200 mA for 480 min higher than unmodified one at twice the
      current. Surface physicochemical properties and morphology were investigated by
      scanning electron microscope, contact angle and X-ray photoelectron spectroscopy.
      The electrochemical characterization of hydrogen evolution reaction was adopted
      to clarify a possible pathway for the higher mineralization of levofloxacin,
      indicating a potential pilot-scale study to the pollution with the similar
      structure.

PMID- 28501566
TI  - DNA methylation regulated gene expression in organ fibrosis.
AB  - DNA methylation is a major epigenetic mechanism to regulate gene expression.
      Epigenetic regulation, including DNA methylation, histone modifications and RNA
      interference, results in heritable changes in gene expression independent of
      alterations in DNA sequence. Epigenetic regulation often occurs in response to
      aging and environment stimuli, including exposures and diet. Studies have shown
      that DNA methylation is critical in the pathogenesis of fibrosis involving
      multiple organ systems, contributing to significant morbidity and mortality.
      Aberrant DNA methylation can silence or activate gene expression patterns that
      drive the fibrosis process. Fibrosis is a pathological wound healing process in
      response to chronic injury. It is characterized by excessive extracellular matrix
      production and accumulation, which eventually affects organ architecture and
      results in organ failure. Fibrosis can affect a wide range of organs, including
      the heart and lungs, and have limited therapeutic options. DNA methylation, like
      other epigenetic process, is reversible, therefore regarded as attractive
      therapeutic interventions. Although epigenetic mechanisms are highly interactive
      and often reinforcing, this review discusses DNA methylation-dependent mechanisms
      in the pathogenesis of organ fibrosis, with focus on cardiac and pulmonary
      fibrosis. We discuss specific pro- and anti-fibrotic genes and pathways regulated
      by DNA methylation in organ fibrosis; we further highlight the potential benefits
      and side-effects of epigenetic therapies in fibrotic disorders.

PMID- 28501571
TI  - Enhanced biodegradation of PAHs in historically contaminated soil by M. gilvum
      inoculated biochar.
AB  - The inoculation of rice straw biochar with PAH-degrading Mycobacterium gilvum
      (1.27 * 1011 +/- 1.24 * 1010 cell g-1), and the subsequent amendment of this
      composite material to PAHs contaminated (677 mg kg-1) coke plant soil, was
      conducted in order to investigate if would enhance PAHs biodegradation in soils.
      The microbe-biochar composite showed superior degradation capacity for
      phenanthrene, fluoranthene and pyrene. Phenanthrene loss in the microbe-biochar
      composite, free cell alone and biochar alone treatments was, respectively, 62.6
      +/- 3.2%, 47.3 +/- 4.1% and non-significant (P > 0.05); whereas for fluoranthene
      loss it was 52.1 +/- 2.3%; non-significant (P > 0.05) and non-significant (P >
      0.05); and for pyrene loss it was 62.1 +/- 0.9%; 19.7 +/- 6.5% and 13.5 +/- 2.8%.
      It was hypothesized that the improved remediation was underpinned by i) biochar
      enhanced mass transfer of PAHs from the soil to the carbonaceous biochar "sink",
      and ii) the subsequent degradation of the PAHs by the immobilized M. gilvum. To
      test this mechanism, a surfactant (Brij 30; 20 mg g-1 soil), was added to impede
      PAHs mass transfer to biochar and sorption. The surfactant increased solution
      phase PAH concentrations and significantly (P < 0.05) reduced PAH degradation in
      the biochar immobilized M. gilvum treatments; indicating the enhanced degradation
      occurred between the immobilized M. gilvum and biochar sorbed PAHs.

PMID- 28501569
TI  - Influence of sulfur on the accumulation of mercury in rice plant (Oryza sativa
      L.) growing in mercury contaminated soils.
AB  - Sulfur (S) is an essential element for plant growth and its biogeochemical
      cycling is strongly linked to the species of heavy metals in soil. In this work,
      the effects of S (sulfate and elemental sulfur) treatment on the accumulation,
      distribution and chemical forms of Hg in rice growing in Hg contaminated soil
      were investigated. It was found that S could promote the formation of iron plaque
      on the root surface and decrease total mercury (T-Hg) and methylmercury (MeHg)
      accumulation in rice grains, straw, and roots. Hg in the root was dominated in
      the form of RS-Hg-SR. Sulfate treatment increased the percentage of RS-Hg-SR to T
      Hg in the rice root and changed the Hg species in soil. The dominant Hg species
      (70%) in soil was organic substance bound fractions. Sulfur treatment decreased
      Hg motility in the rhizosphere soils by promoting the conversion of RS-Hg-SR to
      HgS. This study is significant since it suggests that low dose sulfur treatment
      in Hg-containing water irrigated soil can decrease both T-Hg and MeHg
      accumulation in rice via inactivating Hg in the soil and promoting the formation
      of iron plaque in rice root, which may reduce health risk for people consuming
      those crops.

PMID- 28501573
TI  - Alterations of DNA methylation in parathyroid tumors.
AB  - Parathyroid tumors are common endocrine neoplasias associated with primary
      hyperparathyroidism, a metabolic disorder characterized by parathormone
      hypersecretion. Parathyroid neoplasia are frequently benign adenomas or multiple
      glands hyperplasia, while malignancies are rare. The epigenetic scenario in
      parathyroid tumors has just begun to be decoded: DNA methylation, histones and
      chromatin modifiers expression have been investigated so far. The main findings
      suggest that DNA methylation and chromatin remodeling are active and deregulated
      in parathyroid tumors, cooperating with genetic alterations to drive the tumor
      phenotype: the tumor suppressors menin and parafibromin, involved in parathyroid
      tumorigenesis, interact with chromatin modifiers, defining distinct epigenetic
      derangements. Many epigenetic alterations identified in parathyroid tumors are
      common to those in human cancers; moreover, some aspects of the epigenetic
      profile resemble epigenetic features of embryonic stem cells. Epigenetic profile
      may contribute to define the heterogeneity of parathyroid tumors and to provide
      targets for new therapeutic approaches.

PMID- 28501572
TI  - Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high
      glucose-cultured lens, and SRA01/04 cells through transforming growth factor
      beta2/phosphoinositide 3-kinase/Akt pathway.
AB  - Diabetic cataract (DC), an identified life-threatening secondary complication of
      diabetes mellitus, has proven to be a dilemma because of its multifactorial
      caused and progression. An increasing number of studies have shown that in
      addition to the maillard reaction, enhanced polyol pathway, and oxidative
      insults, epithelial mesenchymal transition (EMT) is related to the prevalence of
      DC. Quercetin, a classic flavonoid with multiple pharmacological effects has been
      reported to possess therapeutic efficacy in the management and treatment of this
      disease. However, the mechanism underlying its therapeutic efficacy in EMT of
      lens epithelial cells (SRA01/04) and contribution to resolving DC remains a
      mystery. Therefore, in this study, we investigated the effects of quercetin on
      EMT of SRA01/04 and high-glucose (HG)-induced lens opacity accompanied by lens
      fibrosis induced by type-1 diabetes. Furthermore, we sought to clarify the
      specific mechanisms underlying these effects. At week 14 after streptozotocin
      (STZ) intraperitoneal administration, diabetic rats showed lens opacity
      accompanied with diminished antioxidant function, enhanced polyol pathway
      activity, and non-enzymatic glycation. Western blotting confirmed EMT in rat
      SRA01/04 cells with significantly increased alpha-smooth muscle actin (alpha-SMA)
      and decreased E-cadherin expressions. Treatment of the lens with quercetin
      ameliorated the oxidative stress, inhibited aldose reductase (AR) activation,
      reduced advanced glycation end product (AGE) production, and finally suppressed
      EMT in the early stages. Our in vitro results showed that high-glucose activated
      the transforming growth factor-beta2/phosphoinositide 3-kinase/protein kinase B
      (TGF-beta2/PI3K/Akt) signalling and EMT in SRA01/04 cells. Further, induced
      oxidative stress, activation of aldose reductase, and accumulation of advanced
      glycation end products were also involved in this process. Quercetin was potent
      enough to effectively ameliorate the high glucose (HG)-induced EMT of SRA01/04
      cells by inhibiting the activation of TGF-beta2/PI3K/Akt, enhancing the
      antioxidant capacity, inhibiting AR activity, and reducing AGE production. From
      the whole animal to tissues, and finally the cellular level, our results provide
      considerable evidence of the therapeutic potential of quercetin for DC. This
      might be due to its inhibition of EMT mediated through inhibition of the TGF
      beta/PI3K/Akt pathway.

PMID- 28501574
TI  - Androgen production in pediatric adrenocortical tumors may occur via both the
      classic and/or the alternative backdoor pathway.
AB  - Children with adrenocortical tumors (ACTs) often present with virilization due to
      high tumoral androgen production, with dihydrotestosterone (DHT) as most potent
      androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and
      the backdoor pathway. Usage of alternate routes for DHT production has been
      reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether
      the backdoor pathway may contribute to the virilization of pediatric ACTs, we
      investigated seven children suffering from androgen producing tumors using
      steroid profiling and immunohistochemical expression studies. All cases produced
      large amounts of androgens of the classic and/or backdoor pathway. Variable
      expression of steroid enzymes was observed in carcinomas and adenomas. We found
      no discriminative pattern. This suggests that enhanced androgen production in
      pediatric ACTs is the result of deregulated steroidogenesis through multiple
      steroid pathways. Thus future treatments of ACTs targeting androgen
      overproduction should consider these novel steroid production pathways.

PMID- 28501575
TI  - The anti-asthmatic drug pranlukast suppresses the delayed-phase vomiting and
      reverses intracellular indices of emesis evoked by cisplatin in the least shrew
      (Cryptotis parva).
AB  - The introduction of second generation serotonin 5-HT3 receptor (5-HT3) antagonist
      palonosetron combined with long-acting substance P neurokinin NK1 receptor (NK1)
      antagonists (e.g. netupitant) has substantially improved antiemetic therapy
      against early- and delayed-phases of emesis caused by highly emetogenic
      chemotherapeutics such as cisplatin. However, the improved efficacy comes at a
      cost that many patients cannot afford. We introduce a new class of antiemetic,
      the antiasthmatic leukotriene CysLT1 receptor antagonist pranlukast for the
      suppression of cisplatin-evoked vomiting. Pranlukast (10mg/kg) by itself
      significantly reduced the mean frequency of vomits (70%) and fully protected
      least shrews from vomiting (46%) during the delayed-phase of cisplatin (10mg/kg)
      evoked vomiting. Although, pranlukast tended to substantially reduce both the
      mean frequency of vomits and the number of shrews vomiting during the early
      phase, these reductions failed to attain significance. When combined with a first
      (tropisetron)- or a second (palonosetron)-generation 5-HT3 receptor antagonist,
      pranlukast potentiated their antiemetic efficacy during both phases of vomiting.
      In addition, pranlukast by itself prevented several intracellular signal markers
      of cisplatin-evoked delayed-vomiting such as phosphorylation of ERK1/2 and PKA.
      When pranlukast was combined with either palonosetron or tropisetron, these
      combinations suppressed the evoked phosphorylation of: i) ERK1/2 during both
      acute- and delayed-phase, ii) PKCalpha/beta at the peak acute-phase, and iii) PKA
      at the peak delayed-phase. The current and our published findings suggest that
      overall behavioral and intracellular signaling effects of pranlukast via blockade
      of CysLT1 receptors generally appear to be similar to the NK1 receptor antagonist
      netupitant with some differences.

PMID- 28501576
TI  - Liraglutide, a glucagon-like peptide-1 analog, induce autophagy and senescence in
      HepG2 cells.
AB  - It has been reported that glucagon-like peptide-1 (GLP-1) agents have been
      associated with both the increased risk of cancer and inhibition of tumor growth
      and metastases. The aim of this study is to evaluate the effect of liraglutide on
      hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism
      related to decreased cell proliferation. Nuclear staining and morphometric
      analysis were also used to verify the process that was taking place after
      treatment with liraglutide, and in order to better understand the mechanism, TGF
      beta1 was performed. HepG2 cells decreased proliferation after liraglutide
      treatment without altering oxidative stress levels. Liraglutide was able to
      induce autophagy and senescence through the increase of TGF-beta1 which possibly
      explains the growth decrease. We have demonstrated that liraglutide has an
      antiproliferative effect in HepG2 cells inducing autophagy and senescence by the
      increase of TGF-beta1.

PMID- 28501577
TI  - Probucol attenuates lipopolysaccharide-induced leukocyte recruitment and
      inflammatory hyperalgesia: effect on NF-kB activation and cytokine production.
AB  - Probucol 4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol) is a synthetic
      molecule clinically used for prevention and treatment of hypercholesterolemia and
      atherosclerosis. Recent studies have shown that the beneficial effects of
      probucol mainly derive from its anti-inflammatory and antioxidant properties.
      Gram-negative bacteria are common infectious agents and their wall components,
      e.g. lipopolysaccharide (LPS), are important elicitors of inflammation. LPS is
      sensed by tissue resident cells and it triggers a Toll-like receptor 4/MyD88
      dependent signaling cascade resulting in endothelial activation, leukocyte
      recruitment and nociception. Therefore the present study aimed to investigate the
      anti-inflammatory and analgesic effects of probucol in models of LPS-induced
      acute inflammation. Probucol at 0.3-30mg/kg was administrated to male Swiss mice
      per oral 1h before intraplantar or intraperitoneal lipopolysaccharide stimulus.
      Probucol at 3mg/kg reduced lipopolysaccharide-induced mechanical and thermal
      hyperalgesia. These effects were accompanied by reduced leukocyte influx and
      cytokine production in both paw skin and peritoneum exudate. Unexpectedly,
      probucol did not alter lipopolysaccharide-induced tissue oxidative stress at anti
      inflammatory /analgesic dose. On the other hand, probucol inhibited
      lipopolysaccharide-induced nuclear factor kappa B (NF-kB) activation in paw
      tissue as well as NF-kB activity in cultured macrophages in vitro, reinforcing
      the inhibitory effect of probucol over the NF-kB signaling pathway. In this
      sense, we propose that probucol acts on resident immune cells, such as
      macrophages, targeting the NF-kB pathway. As a result, it prevents the
      amplification and persistence of the inflammatory response by attenuating NF-kB
      dependent cytokine production and leukocyte recruitment explaining its analgesic
      effects as well.

PMID- 28501578
TI  - Anhydroicaritin, a SREBPs inhibitor, inhibits RANKL-induced osteoclastic
      differentiation and improves diabetic osteoporosis in STZ-induced mice.
AB  - Nowadays, more and more attention has been paid to osteoporosis caused by
      diabetes mellitus. Elevated levels of pro-inflammatory cytokines in diabetic
      patients activate the activity of osteoclasts through the RANKL/OPG pathway. The
      nuclear transcription factor SREBP2, a master regulator of cholesterol
      metabolism, has been found involved in osteoclastogenesis. In our previous study,
      we have identified anhydroicaritin as a potent inhibitor of transcription factor
      SREBPs, which improves dyslipidemia and insulin resistance. In this study, we
      demonstrated that anhydroicaritin could also decrease the level of SREBP2 and its
      target genes in osteoclasts induced by RANKL without significant cytotoxicity.
      Moreover, anhydroicaritin suppressed RANKL-induced osteoclasts differentiation.
      In STZ-induced diabetic mice model, we found that the osteoclasts were largely
      increased accompanied with deterioration of bone structure. Anhydroicaritin
      decreased the level of blood glucose and alleviated insulin resistance. More
      importantly, anhydroicaritin inhibited osteoclast differentiation and rescued
      diabetes-induced bone loss in vivo. In conclusion, anhydroicaritin, a potent
      SREBP2 inhibitor, inhibits the osteoclasts formation and improves diabetes
      induced bone loss.

PMID- 28501579
TI  - Eicosapentaenoic acid monoglyceride resolves inflammation in an ex vivo model of
      human peripheral blood mononuclear cell.
AB  - Phosphorylation and activation of p38 MAPK and NFkappaB pathways, along with the
      resulting overproduction of interleukin IL-1beta, IL-6, and tumor necrosis factor
      a (TNFalpha) is a hallmark of inflammatory disorders. Omega-3 polyunsaturated
      fatty acid (n-3 PUFA) supplementations are known to exert anti-inflammatory
      properties by reduction of keys cytokines and enzymes involved in inflammation.
      Here, we investigated the anti-inflammatory pathways and mediators modulated by
      eicosapentaenoic acid monoglyceride (MAG-EPA) on human peripheral blood
      mononuclear cells (PBMCs) from healthy donors and stimulated, ex vivo, with
      lipopolysaccharide (LPS). LPS stimulation increased p38 MAPK and NFkappaB
      phosphorylation, which was abolished by MAG-EPA treatments. Concomitantly, MAG
      EPA also abolished LPS-induced inflammation in PBMCs by reducing IL-1beta, IL-6,
      and TNFalpha cytokines at protein and transcript levels. Moreover, MAG-EPA
      decreased the levels of HIF1alpha in LPS-induced human PBMCs. Results also
      revealed a decreased of pro-inflammatory enzymes such as Cyclooxygenase-2 (COX-2)
      and 5-lipoxygenase (5-LOX) in LPS-induced PBMCs. Altogether, the present data
      suggest that MAG-EPA, represents a new potential therapeutic strategy for
      resolving inflammation in inflammatory disorders including autoimmune diseases,
      allergies, asthma, arthritis and cancer.

PMID- 28501580
TI  - Can the acute magnetic resonance imaging features reflect neurologic prognosis in
      patients with cervical spinal cord injury?
AB  - BACKGROUND CONTEXT: Several prognostic studies looked for an association between
      the degree of spinal cord injury (SCI), as depicted by primary magnetic resonance
      imaging (MRI) within 72 hours of injury, and neurologic outcome. It was not
      clearly demonstrated whether the MRI at any time correlates with neurologic
      prognosis. PURPOSE: The purpose of the present study was to investigate the
      relationship between acute MRI features and neurologic prognosis, especially
      walking ability of patients with cervical spinal cord injury (CSCI). Moreover, at
      any point, MRI was clearly correlated with the patient's prognosis. STUDY DESIGN:
      Retrospective image study. PATIENT SAMPLE: From January 2010 to October 2015, 102
      patients with CSCI were treated in our hospital. Patients who were admitted to
      our hospital within 3 days after injury were included in this study. The
      diagnosis was 78 patients for CSCI with no or minor bony injury and 24 patients
      for CSCI with fracture or dislocation. A total of 88 men and 14 women were
      recruited, and the mean patient age was 62.6 years (range, 16-86 years).
      Paralysis at the time of admission was graded as A in 32, B in 15, C in 42, and D
      in 13 patients on the basis of the American Spinal Injury Association (ASIA)
      impairment scale. Patients with CSCI with fracture or dislocation were treated
      with fixation surgery and those with CSCI with no or minor bony injury were
      treated conservatively. Patients were followed up for an average of 168 days
      (range, 25-496 days). OUTCOME MEASURES: Neurologic evaluation was performed using
      the ASIA motor score and the modified Frankel grade at the time of admission and
      discharge. METHODS: Magnetic resonance imaging was performed for all patients at
      admission. Using the MRI sagittal images, we measured the vertical diameter of
      intramedullary high-intensity changed area with T2-weighted images at the injured
      segment. We studied separately the patients divided into two groups: 0-1 day
      admission after injury, and 2-3 days admission after injury. We evaluated the
      relationship between the vertical diameter of T2 high-intensity changed area in
      MR images and neurologic outcome in these two groups. This study does not contain
      any conflict of interest. RESULTS: In the group admitted at 0-1 day after injury,
      there was a relationship between the vertical diameter of T2 high-intensity area
      in MR image and the ASIA motor score at admission and at discharge, but
      correlation coefficient was low (0.3766 at admission and 0.4239 at discharge). On
      the other hand, in the group admitted at 2-3 days after injury, there was a
      significant relationship between the vertical diameter of T2 high-intensity area
      in MR image and the ASIA motor score at admission and at discharge, and
      correlation coefficient was very high (0.6840 at admission and 0.5293 at
      discharge). In the group admitted at 2-3 days after injury, a total of 17
      patients (68%) recovered to walk with or without a cane. Receiver operating
      characteristic (ROC) curve analysis demonstrated that the optimal vertical
      diameter of T2 high-intensity area cutoffvalue for patients who were able to walk
      at discharge was 45.8 mm. If the vertical diameter of T2 high-intensity area
      cutoff value was 45 mm, there was a significant positive correlation with being
      able to walk at discharge (p<.0001). CONCLUSIONS: From our study, 2-3 days after
      injury, a significant relationship was observed between the vertical diameter of
      T2 high-intensity area and the neurologic prognosis at discharge. Zero to 1 day
      after injury, the relationship between the vertical diameter of T2 high-intensity
      area and the neurologic prognosis at discharge was weak. Neurologic prognosis is
      more correlated with MRI after 2-3 days after the injury. If the vertical
      diameter of T2 high-intensity area was <45 mm, the patients were able to walk
      with or without a cane at discharge. T2 high-intensity changed area can reflect
      the neurologic prognosis in patients with CSCI.

PMID- 28501581
TI  - Longer Observation Time Increases Proportion of Neoplasms Detected by
      Esophagogastroduodenoscopy.
AB  - BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is commonly used to detect
      upper gastrointestinal (GI) neoplasms. However, there is little evidence that
      longer examination time increases rate of detection of upper GI neoplasia. We
      investigated the association between length of time spent performing a normal
      screening EGD and rate of neoplasm detection. METHODS: We performed a
      retrospective analysis of data from 111,962 subjects who underwent EGD as part of
      a comprehensive health-screening program from January 2009 to December 2015 in
      Korea. Endoscopy findings were extracted from reports prepared by 14 board
      certified endoscopists. Endoscopists were classified as fast or slow based on
      their mean examination time for a normal EGD without biopsy during their first
      year of the study. All endoscopists used the same endoscopy unit. We obtained
      findings from histologic analyses of GI biopsies from patient records; positive
      findings were defined as the detection of neoplasms (esophageal, gastric, or
      duodenal lesions). We examined the association between examination time and
      proportions of neoplasms detected. The primary outcome measure was the rate of
      neoplasm detection for each endoscopist (total number of neoplastic lesions
      detected divided by the number of subjects screened) and as the proportion of
      subjects with at least 1 neoplastic lesion. RESULTS: The mean examination time
      was 2 minutes 53 seconds. Using 3 minutes as a cutoff, we classified 8
      endoscopists as fast (mean duration, 2:38 +/- 0:21 minutes) and 6 endoscopists as
      slow (mean duration, 3:25 +/- 0:19 minutes). Each endoscopist's mean examination
      time correlated with their rate of neoplasm detection (R2 = 0.54; P = .046). Fast
      endoscopists identified neoplasms in the upper GI tract in 0.20% of patients,
      whereas slow endoscopists identified these in 0.28% of patients (P = .0054). The
      frequency of endoscopic biopsy varied among endoscopists (range, 6.9%-27.8%) and
      correlated with rate of neoplasm detection (R2 = 0.76; P = .0015). On
      multivariable analysis, slow endoscopists were more likely to detect gastric
      adenomas or carcinomas than fast endoscopists (odds ratio, 1.52; 95% CI, 1.17
      1.97). CONCLUSIONS: In a retrospective analysis of data from more than 100,000
      subjects who underwent EGD in a screening program, we found slow endoscopists
      detected a higher proportion of neoplasms than fast endoscopists. Examination
      time is therefore a useful indicator of quality for EGD.

PMID- 28501582
TI  - Molecular detection of rifampicin resistance by GeneXpert(r) assay among treated
      and untreated pulmonary tuberculosis patients from Khyber Pakhtunkhwa, Pakistan.
AB  - OBJECTIVES: Drug-resistant tuberculosis (TB) is an emerging health problem.
      Rifampicin (RIF) is the major first-line drug against TB. RIF resistance can be
      used as a marker for the detection of multidrug-resistant TB (MDR-TB). The
      purpose of this study was to determine the RIF resistance pattern of
      Mycobacterium tuberculosis complex isolates among treated and untreated patients
      in Khyber Pakhtunkhwa, Pakistan. METHODS: A total of 349 drug-treated and
      untreated TB-diagnosed patients were enrolled in this study. RIF resistance was
      detected using a GeneXpert(r) assay for amplification of the RIF resistance
      determining region (RRDR) region of the rpoB gene. RESULTS: The overall
      prevalence of RIF resistance was 5.2% (18/349). Among 49 untreated TB patients, 3
      samples (6.1%) were found resistant to RIF. Among 235 patients with a category 1
      treatment regimen, 10 samples (4.3%) were resistant to RIF, whilst among 65
      patients with a category 2 (Cat-2) treatment regimen, 5 samples (7.7%) were
      resistant to RIF. A comparison based on patient sex revealed high RIF resistance
      among male compared with female patients. RIF resistance was highest (4/21;
      19.0%) in the 21-40 years age group among Cat-2 patients. CONCLUSIONS: The
      overall prevalence of RIF resistance was high among treated and untreated TB
      patients. These findings will be helpful for better monitoring and management of
      RIF resistance in TB patients from Khyber Pakhtunkhwa, Pakistan.

PMID- 28501583
TI  - Combining NMR and small angle X-ray scattering for the study of biomolecular
      structure and dynamics.
AB  - Small-angle X-ray scattering (SAXS) and Nuclear Magnetic Resonance (NMR) are
      established methods to analyze the structure and structural transitions of
      biological macromolecules in solution. Both methods are directly applicable to
      near-native macromolecular solutions and allow one to study structural responses
      to physical and chemical changes or ligand additions. Whereas SAXS is applied to
      elucidate overall structure, interactions and flexibility over a wide range of
      particle sizes, NMR yields atomic resolution detail for moderately sized
      macromolecules. NMR is arguably the most powerful technique for the experimental
      analysis of dynamics. The joint application of these two highly complementary
      techniques provides an extremely useful approach that facilitates comprehensive
      characterization of biomacromolecular solutions.

PMID- 28501584
TI  - Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic
      cancer via alteration of oxidative stress and inflammatory mechanism.
AB  - Present study, was an effort to scrutinize the molecular and biochemical role of
      ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in
      Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for
      induction of HCC in rats. The rats were divided into eight various groups. DEN
      induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in
      combination for the period of 12th weeks. The protocol was terminated after the
      16th week. Exposure of DEN up-regulated the levels of different serum biochemical
      parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the
      level of High density lipoprotein (HDL) in Wistar rats along with the alteration
      in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor
      (TNF-alpha) and Interleukin-1beta (IL-1beta) with decrease in body weight.
      Macroscopic evaluation, revealed DEN group rats confirmed the expansion of
      hepatic nodules, which were reduced by the individual treatment of ibuprofen and
      thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the
      significant reduction of hepatic nodules. Further, this combination possesses the
      significant chemoprotective effect in DEN-induced HCC by restoring the hepatic
      enzymes and other biomarkers along with an alteration in pro-inflammatory
      cytokines. The above result concludes that ibuprofen and thiamine combination
      possess potent anti-cancerous activity.

PMID- 28501585
TI  - Proteolytic Post-Translational Processing of Adhesins in a Pathogenic Bacterium.
AB  - Mollicutes, including mycoplasmas and spiroplasmas, have been considered as good
      representatives of the " minimal cell " concept: these wall-less bacteria are
      small in size and possess a minimal genome and restricted metabolic capacities.
      However, the recent discovery of the presence of post-translational modifications
      unknown so far, such as the targeted processing of membrane proteins of
      mycoplasma pathogens for human and swine, revealed a part of the hidden
      complexity of these microorganisms. In this study, we show that in the
      phytopathogen, insect-vectored Spiroplasma citri GII-3 adhesion-related protein
      (ScARP) adhesins are post-translationally processed through an ATP-dependent
      targeted cleavage. The cleavage efficiency could be enhanced in vitro when
      decreasing the extracellular pH or upon the addition of polyclonal antibodies
      directed against ScARP repeated units, suggesting that modification of the
      surface charge and/or ScARP conformational changes could initiate the cleavage.
      The two major sites for primary cleavage are localized within predicted
      disordered regions and do not fit any previously reported cleavage motif; in
      addition, the inhibition profile and the metal ion requirements indicate that
      this post-translational modification involves at least one non-conventional
      protease. Such a proteolytic process may play a role in S. citri colonization of
      cells of the host insect. Furthermore, our work indicates that post-translational
      cleavage of adhesins represents a common feature to mollicutes colonizing
      distinct hosts and that processing of surface antigens could represent a way to
      make the most out of a minimal genome.

PMID- 28501586
TI  - Structural Molecular Biology-A Personal Reflection on the Occasion of John
      Kendrew's 100th Birthday.
AB  - Here, I discuss the development and future of structural molecular biology,
      concentrating on the eukaryotic transcription machinery and reflecting on John
      Kendrew's legacy from a personal perspective.

PMID- 28501587
TI  - Functional Requirements for DjlA- and RraA-Mediated Enhancement of Recombinant
      Membrane Protein Production in the Engineered Escherichia coli Strains SuptoxD
      and SuptoxR.
AB  - In previous work, we have generated the engineered Escherichia coli strains
      SuptoxD and SuptoxR, which upon co-expression of the effector genes djlA or rraA,
      respectively, are capable of suppressing the cytotoxicity caused by membrane
      protein (MP) overexpression and of producing dramatically enhanced yields for a
      variety of recombinant MPs of both prokaryotic and eukaryotic origin. Here, we
      investigated the functional requirements for DnaJ-like protein A (DjlA)- and
      regulator of ribonuclease activity A (RraA)-mediated enhancement of recombinant
      MP production in these strains and show that: (i) DjlA and RraA act
      independently, that is, the beneficial effects of each protein on recombinant MP
      production occur through a mechanism that does not involve the other, and in a
      non-additive manner; (ii) full-length and membrane-bound DjlA is required for
      exerting its beneficial effects on recombinant MP production in E. coli SuptoxD;
      (iii) the MP production-promoting properties of DjlA in SuptoxD involve the
      action of the molecular chaperone DnaK but do not rely on the activation of the
      regulation of capsular synthesis response, a well-established consequence of djlA
      overexpression; (iv) the observed RraA-mediated effects in E. coli SuptoxR
      involve the ribonucleolytic activity of RNase E, but not that of its paralogous
      ribonuclease RNase G; and (v) DjlA and RraA are unique among similar E. coli
      proteins in their ability to promote bacterial recombinant MP production. These
      observations provide important clues about the molecular requirements for
      suppressed toxicity and enhanced MP accumulation in SuptoxD/SuptoxR and will
      guide future studies aiming to decipher the exact mechanism of DjlA- and RraA
      mediated enhancement of recombinant MP production in these strains.

PMID- 28501588
TI  - Oligomeric Structure of Anabaena Sensory Rhodopsin in a Lipid Bilayer Environment
      by Combining Solid-State NMR and Long-range DEER Constraints.
AB  - Oligomerization of membrane proteins is common in nature. Here, we combine spin
      labeling double electron-electron resonance (DEER) and solid-state NMR (ssNMR)
      spectroscopy to refine the structure of an oligomeric integral membrane protein,
      Anabaena sensory rhodopsin (ASR), reconstituted in a lipid environment. An
      essential feature of such a combined approach is that it provides structural
      distance restraints spanning a range of ca 3-60A while using the same sample
      preparation (i.e., mutations, paramagnetic labeling, and reconstitution in lipid
      bilayers) for both ssNMR and DEER. Direct modeling of the multispin effects on
      DEER signal allowed for the determination of the oligomeric order and for
      obtaining long-range DEER distance restraints between the ASR trimer subunits
      that were used to refine the ssNMR structure of ASR. The improved structure of
      the ASR trimer revealed a more compact packing of helices and side chains at the
      intermonomer interface, compared to the structure determined using the ssNMR data
      alone. The extent of the refinement is significant when compared with typical
      helix movements observed for the active states of homologous proteins. Our
      combined approach of using complementary DEER and NMR measurements for the
      determination of oligomeric structures would be widely applicable to membrane
      proteins where paramagnetic tags can be introduced. Such a method could be used
      to study the effects of the lipid membrane composition on protein oligomerization
      and to observe structural changes in protein oligomers upon drug, substrate, and
      co-factor binding.

PMID- 28501590
TI  - Are we ready to take ECPR on the road? Maybe....

PMID- 28501591
TI  - What you ask for is what you get: A practical approach for early cognitive
      screening and the potential for individualized support after cardiac arrest.

PMID- 28501589
TI  - Genetic modifiers of multiple sclerosis progression, severity and onset.
AB  - The genetic contribution to clinical outcomes for multiple sclerosis (MS) has yet
      to be defined. We performed exome sequencing analysis in 100 MS patients
      presenting opposite extremes of clinical phenotype (discovery cohort), and
      genotyped variants of interest in 2016 MS patients (replication cohort). Linear
      and logistic regression analyses were used to identify significant associations
      with disease course, severity and onset. Our analysis of the discovery cohort
      nominated 38 variants in 21 genes. Replication analysis identified PSMG4 p.W99R
      and NLRP5 p.M459I to be associated with disease severity (p=0.002 and 0.008).
      CACNA1H p.R1871Q was found associated with patients presenting relapsing
      remitting MS at clinical onset (p=0.028) whereas NLRP5 p.M459I and EIF2AK1
      p.K558R were associated with primary progressive disease (p=0.031 and 0.023). In
      addition, PSMG4 p.W99R and NLRP5 p.R761L were found to correlate with an earlier
      age at MS clinical onset, and MC1R p.R160W with delayed onset of clinical
      symptoms (p=0.010-0.041).

PMID- 28501592
TI  - Endoscopic and molecular characterization of colorectal sessile serrated
      adenoma/polyps with cytologic dysplasia.
AB  - BACKGROUND AND AIMS: Sessile serrated adenoma/polyps (SSA/Ps), which are
      precursor lesions of colorectal cancer (CRC) with BRAF mutation and the CpG
      island methylator phenotype (CIMP), develop cytologic dysplasia (CD) during the
      progression of colorectal tumorigenesis. In the present study we aimed to clarify
      the endoscopic and molecular signatures of SSA/Ps, with and without CD. METHODS:
      A series of 208 serrated lesions, including 41 hyperplastic polyps, 90 SSA/Ps, 33
      SSA/Ps with CD, and 44 traditional serrated adenomas, were observed and resected
      using magnifying endoscopy. BRAF and KRAS mutations and methylation of CIMP
      markers (MINT1, MINT2, MINT12, MINT31, and p16) were analyzed through
      pyrosequencing. Molecular alterations were then compared with endoscopic and
      pathologic characteristics. RESULTS: Among SSA/Ps without CD, the Type II-Open
      pit pattern (Type II-O), BRAF mutation, and CIMP were tightly associated with a
      proximal colon location. SSA/Ps in the distal colon infrequently exhibited Type
      II-O and CIMP. By contrast, most SSA/Ps with CD showed Type II-O plus adenomatous
      pit patterns (Type III or IV), BRAF mutation, and CIMP, irrespective of their
      locations. CONCLUSIONS: Our results suggest that the Type II-O plus III/IV pit
      pattern is a common feature of SSA/Ps with CD in both the proximal and distal
      colon and that this pit pattern is a hallmark of serrated lesions at high risk of
      developing into CRCs.

PMID- 28501593
TI  - Transmural ablation of the normal porcine common bile duct with catheter-directed
      irreversible electroporation is feasible and does not affect duct patency.
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate the feasibility and
      early safety of catheter-directed irreversible electroporation (IRE) of the
      normal common bile duct (CBD) in swine. METHODS: IRE (2000 V, 90 pulses, 100 MUs
      pulse) was performed in the CBD of 6 Yorkshire pigs using a catheter electrode
      under endoscopic guidance. Ductal patency was assessed with immediate retrograde
      cholangiography and contrast-enhanced CT imaging at 1 or 7 days after treatment.
      Animals were killed at either 1 day (n = 4, 2 ablations/animal) or 7 days (n = 2,
      1 ablation/animal) after treatment. The biliary tract was extracted en bloc and
      the length of the ablation along the CBD mucosa was measured. The depth of
      ablation was quantified using cross-sections of the treated CBD wall stained with
      hematoxylin and eosin. Single-sample hypothesis testing was performed to verify
      whether the depth of ablation in the CBD was a representative outcome of IRE
      treatment. RESULTS: IRE of the CBD did not result in perforation or obstruction
      of the organ at 1 or 7 days after treatment. The length of ablation along the CBD
      mucosa was 17.27 +/- 5.55 mm on day 1 samples, and transmural ablation of the CBD
      wall was a representative outcome of the treatment (7/8 samples, P < .05). Day 1
      samples demonstrated loss of epithelium, transmural necrosis, with preservation
      of lumen integrity. Day 7 samples demonstrated re-epithelialization, with diffuse
      transmural fibrosis of the CBD wall. These findings were absent from sham tissue
      samples. CONCLUSIONS: Intraluminal catheter-directed IRE is feasible and safe for
      full-thickness ablation of the normal porcine CBD without affecting lumen patency
      up to 1 week after treatment.

PMID- 28501594
TI  - The SAFE-T assessment tool: derivation and validation of a web-based application
      for point-of-care evaluation of gastroenterology fellow performance in
      colonoscopy.
AB  - BACKGROUND AND AIMS: Attending assessment is a critical part of endoscopic
      education for gastroenterology fellows. The aim of this study was to develop and
      validate a concise assessment tool to evaluate real-time fellow performance in
      colonoscopy administered via a web-based application. METHODS: The Skill
      Assessment in Fellow Endoscopy Training (SAFE-T) tool was derived as a novel 5
      question evaluation tool that captures both summative and formative feedback
      adapted into a web-based application. A prospective study of 15 gastroenterology
      fellows (5 fellows each from years 1 to 3 of training) was performed using the
      SAFE-T tool. An independent reviewer evaluated a subset of these procedures and
      completed the SAFE-T tool and Mayo Colonoscopy Skills Assessment Tool (MCSAT) for
      reliability testing. RESULTS: Twenty-six faculty completed 350 SAFE-T evaluations
      of the 15 fellows in the study. The mean SAFE-T overall score (year 1, 2.00; year
      2, 3.84; year 3, 4.28) differentiated each sequential fellow year of training (P
      < .0001). The mean SAFE-T overall score decreased with increasing case complexity
      score, with straightforward cases compared with average cases (4.07 vs 3.50, P <
      .0001), and average cases compared with challenging cases (3.50 vs 3.08, P =
      .0134). In dual-observed procedures, the SAFE-T tool showed excellent inter-rater
      reliability with a kappa agreement statistic of 0.898 (P < .0001). Correlation of
      the SAFE-T overall score with the MCSAT overall hands-on and individual motor
      scores was excellent (each r > 0.90, P < .0001). CONCLUSIONS: We developed and
      validated the SAFE-T assessment tool, a concise and web-based means of assessing
      real-time gastroenterology fellow performance in colonoscopy.

PMID- 28501596
TI  - A novel FbFP-based biosensor toolbox for sensitive in vivo determination of
      intracellular pH.
AB  - The intracellular pH is an important modulator of various bio(techno)logical
      processes such as enzymatic conversion of metabolites or transport across the
      cell membrane. Changes of intracellular pH due to altered proton distribution can
      thus cause dysfunction of cellular processes. Consequently, accurate monitoring
      of intracellular pH allows elucidating the pH-dependency of (patho)physiological
      and biotechnological processes. In this context, genetically encoded biosensors
      represent a powerful tool to determine intracellular pH values non-invasively and
      with high spatiotemporal resolution. We have constructed a toolbox of novel
      genetically encoded FRET-based pH biosensors (named Fluorescence Biosensors for
      pH or FluBpH) that utilizes the FMN-binding fluorescent protein EcFbFP as donor
      domain. In contrast to many fluorescent proteins of the GFP family, EcFbFP
      exhibits a remarkable tolerance towards acidic pH (pKa~3.2). To cover the broad
      range of physiologically relevant pH values, three EYFP variants exhibiting pKa
      values of 5.7, 6.1 and 7.5 were used as pH-sensing FRET acceptor domains. The
      resulting biosensors FluBpH 5.7, FluBpH 6.1 and FluBpH 7.5 were calibrated in
      vitro and in vivo to accurately evaluate their pH indicator properties. To
      demonstrate the in vivo applicability of FluBpH, changes of intracellular pH were
      ratiometrically measured in E. coli cells during acid stress.

PMID- 28501597
TI  - Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic
      application in erythroid disorders.
AB  - Iron is required for hemoglobin production, and it plays a key role during
      erythropoiesis. Systemic iron homeostasis is mainly negatively regulated by the
      peptide hormone hepcidin, coded by the gene HAMP. Hepcidin excess may cause iron
      deficiency, iron-restricted erythropoiesis, and anemia. Conversely, hepcidin
      insufficiency leads to iron overload and oxidative damage in multiple tissues.
      During regulation of hepcidin synthesis, multiple promoter elements in the HAMP
      gene respond to variable signaling pathways corresponding to different
      extracellular situations. It has been reported that hepcidin expression can be
      suppressed by secreted erythroid factors, including GDF15, TWSG1, GDF11, and
      ERFE, thereby increasing iron availability for hemoglobin synthesis. These
      potential erythroid factors act via intricate mechanisms that remain
      controversial. However, it is clear that hepcidin affects erythropoiesis, and
      promising therapies targeting hepcidin have been developed to treat erythroid
      disorders. These therapeutic strategies include suppressing or activating HAMP
      gene expression, mimicking or activating hepcidin activity, and blocking the
      ability of hepcidin to bind to its target ferroportin.

PMID- 28501595
TI  - Corticolimbic circuitry in the modulation of chronic pain and substance abuse.
AB  - The transition from acute to chronic pain is accompanied by increased engagement
      of emotional and motivational circuits. Adaptations within this corticolimbic
      circuitry contribute to the cellular and behavioral maladaptations associated
      with chronic pain. Central regions within the corticolimbic brain include the
      mesolimbic dopamine system, the amygdala, and the medial prefrontal cortex. The
      evidence reviewed herein supports the notion that chronic pain induces
      significant changes within these corticolimbic regions that contribute to the
      chronicity and intractability of pain. In addition, pain-induced changes in
      corticolimbic circuitry are poised to impact motivated behavior and reward
      responsiveness to environmental stimuli, and may modulate the addiction liability
      of drugs of abuse, such as opioids.

PMID- 28501598
TI  - Microgramma vacciniifolia (Polypodiaceae) fronds contain a multifunctional lectin
      with immunomodulatory properties on human cells.
AB  - In this study, we report the purification and characterization of a
      multifunctional lectin (MvFL) from Microgramma vacciniifolia fronds as well as
      its immunomodulatory properties on human peripheral blood mononuclear cells
      (PBMCs). MvFL (pI 4.51; 54kDa) is a glycoprotein able to inhibit trypsin activity
      and that has sequence similarities (32% coverage) with a plant RNA-binding
      protein. Hemagglutinating activity of MvFL was not altered by heating at 100
      degrees C for 30min, but was reduced in alkaline pH (8.0 and 9.0). Fluorimetric
      analyses showed that this lectin did not undergo marked conformational changes
      when heated. However, the MvFL conformation changed depending on the pH. MvFL at
      6.25-25MUg/mL was not cytotoxic to lymphocytes present among PBMCs. The PBMCs
      incubated for 24h with the lectin (12.5MUg/mL) showed increased TNF-alpha, IFN
      gamma, IL-6, IL-10, and nitric oxide production. MvFL also stimulated T
      lymphocytes from PBMCs to differentiate into CD8+ cells. The activation
      (indicated by CD28 expression) of these cells was also stimulated. In conclusion,
      MvFL is a heat-stable and multifunctional protein, with both lectin and trypsin
      inhibitor activities, and capable of inducing predominantly a Th1 response in
      human PBMCs as well as activation and differentiation of T lymphocytes.

PMID- 28501599
TI  - pH induced single step shift of hydrophobic patches followed by formation of an
      MG state and an amyloidogenic intermediate in Lima Bean Trypsin Inhibitor (LBTI).
AB  - Lima Bean Trypsin Inhibitor (LBTI) is 83 residues monomeric protein of 9.0 KDa,
      consisting of six antiparallel beta-strands and can undergo concentration
      dependant dimerization. We have tried to characterize folding intermediates of
      LBTI under equilibrium denaturation conditions. We have used various
      spectroscopic and microscopic techniques to understand the folding and misfolding
      pathways. LBTI forms molten globule structure at pH 2 and amyloidiogenic
      intermediate state (Ia) at pH 4. pH induced Shifting of surface exposed
      hydrophobic patches and that followed by withdrawal of the lone tyrosine residue
      (Y69) towards nonpolar environment have been reported. Denaturation profile of
      native and molten globule (MG) states of LBTI in presence of guanidine
      hydrochloride show sigmoidal curves with non-coincidental and irreversible
      behaviour in both states. Concentration dependent amyloid fibril formation was
      confirmed by Thioflavin T and Congo Red binding and its morphology was studied by
      transmission electron microscopy (TEM). This is the first report on biophysical
      characterization of folding intermediates of LBTI and its aggregation behaviour
      to the best of our knowledge.

PMID- 28501600
TI  - Development of a human epidermal growth factor derivative with EGFR-blocking and
      depleted biological activities: A comparative in vitro study using EGFR-positive
      breast cancer cells.
AB  - Epidermal growth factor (EGF) is a local growth factor that stimulates cell
      growth, proliferation, and differentiation by binding to its receptor EGFR. EGF
      and EGFR are involved in many aspects of the development of carcinomas. Because
      EGFR has been found to be over-expressed in many tumors of epithelial origin, it
      is a potential target for antitumor therapy. In this study we designed a mutated
      form of hEGF (mEGF) with a deletion of four amino acids residues (Gln43, Tyr44,
      Arg45 and Asp46) in order to show importance of Leu spatial location for EGFR
      binding/activation. Expression vector pET32a+ and E. Coli, strain Rosetta-gami B
      (DE3) were used to enhance solubility of the recombinant protein with yielding
      approximately 10mg/l of cell culture. The purified cleaved hEGF as well as non
      cleaved fusion protein were biologically active, which was confirmed by their
      equal ability to stimulate proliferation of MCF7 cells. The mEGF showed
      specificity and high affinity for EGFR binding, however binding affinity of mEGF
      for EGFR was reduced about 11.5 fold compared with that of hEGF. The mEGF effect
      on the MCF7 cell proliferation had a relatively different outcome; mEGF simulated
      differential cell growth in a dose dependent manner. On the other hand, in MDA
      MB468 cells, hEGF and mEGF induced growth inhibition, which was much more severe
      for hEGF than that of mEGF. Also, hEGF strongly induced the phosphorylation of
      EGF receptor in MDA-MB468 cells while mEGF induced poor EGFR phosphorylation. The
      same observations were also made for migration of cancer cells, especially
      induction of MDA-MB468 migration by mEGF was significantly lower than that of
      hEGF, suggesting a connection between tyrosine phosphorylation of EGFR and cell
      migration. Docking analysis revealed that the binding affinity and the buried
      surface area of mEGF to EGFR complex are lower than those of hEGF/EGFR. Although
      theoretical studies confirmed reduction in mEGF-EGFR binding affinity, the data
      of the present study indicate that mEGF is a potential EGFR blocker but may
      highlight it as excellent delivery agent of protein/non-protein toxins as well as
      for alpha-, beta-, gamma-emitting radio-immunotherapy.

PMID- 28501601
TI  - Novel inhibitors of tyrosinase produced by the 4-substitution of TCT (P).
AB  - Novel Tyrosinase Inhibitors of 4-functionalized Thiophene-2-carbaldehyde
      thiosemicarbazone (TCT) derivatives (1-8) had been synthesized and
      Spectrofluorimetry, 1H and 13C NMR titration and Molecular docking had been used
      to investigate their inhibitory activities and mechanisms on tyrosinase. The
      results showed that the inter-molecular interactions or hydrogen bond formation
      by increasing length of carbon chain or introducing benzene ring to the 4
      functionalized ester group promoted or stabilized formation of complexes between
      modifier and tyrosinase, and enhanced the inhibitory activity of modifiers. The
      inhibitory activity of 4-benzoy methoxy-TCT was much stronger than that of any
      other synthesized tested modifiers, which was well explained by molecular docking
      and further verified by spectrofluorimetry and NMR titration by assuming that
      there existed an inter-molecular interaction besides formation of hydrogen bonds
      between the amino acid residues ASN260, GLU256, HIS85 of enzyme and the
      modifier.We concluded that 4-benzoy methoxy substitution of TCT was a good route
      obtaining novel tyrosinase inhibitors and deserved further studies.

PMID- 28501602
TI  - Soluble epoxide hydrolase inhibitory activity of components from Leonurus
      japonicus.
AB  - One new compound, 10-methoxy-leonurine (1), and four known compounds (2-5) were
      purified by silica gel, C-18, and Sephadex LH-20 column chromatography from
      Leonurus japonicus. Their structures were elucidated using one-dimensional
      (1D)/two-dimensional (2D)-nuclear magnetic resonance (NMR), high-resolution (HR)
      electrospray ionization (ESI) mass spectrometry (MS). The compounds were
      evaluated to determine their inhibition of the catalysis of soluble epoxide
      hydrolase (sEH). According to the results from in vitro analyses, compounds 1 and
      2, which contain guanidine and flavonoid (3), were determined to be potential
      inhibitors of this enzyme. All compounds were revealed to be non-competitive
      inhibitors according to Lineweaver-Burk plots. Furthermore, in silico molecular
      docking indicated that compounds 1-3 are bound to sEH in a similar fashion and
      have stable binding energies, as calculated by AutoDock 4.2. Molecular dynamics
      determined the root-mean-square deviation (RMSD), total energy, RMS fluctuation
      (RMSF), hydrogen bonds, and distance of the complex according to time.

PMID- 28501603
TI  - Polyelectrolyte complexes based on alginate/tanfloc: Optimization,
      characterization and medical application.
AB  - Hydrogels based on alginate and tanfloc (a cationic biopolymer obtained from
      natural condensed tannins) were successfully prepared. Tanfloc (TN) presents high
      aqueous solubility at pHs lower than 10; it contains substituted amino sites and
      molar weight of ca. 600,000gmol-1. A factorial design (22) was used to optimize
      the yield of alginate/tanfloc polyelectrolyte complexes (PECs). Dialysis
      recovered the overplus of alginate (AG) no complexed with TN. These materials
      were characterized by thermal analyses (TGA/DTG and DSC), zeta potential, and
      FTIR, while SEM technique depicted a rough surface on AG/TN complex, containing
      non-homogeneous pores. Indeed, the AG and TN were tailored to elicit scaffold
      materials with outstanding cytocompatibility, mainly upon mouse preosteoblastic
      cells because of reconstruction of bone tissues (119% at 10days). The AG/TN
      complex also displayed antioxidant and bactericidal activities against
      Staphylococcus aureus (S. aureus). Besides, the pristine TN fostered
      bacteriostatic and bactericidal performances towards S. aureus and Escherichia
      coli. However, for our best knowledge, no studies were still carried out on TN
      and TN-based materials for medical purpose.

PMID- 28501604
TI  - High production, purification, biochemical characterization and gene analysis of
      a novel catalase from the thermophilic bacterium Ureibacillus thermosphaericus
      FZSF03.
AB  - A catalase-producing thermophilic bacterium, Ureibacillus thermosphaericus
      FZSF03, was isolated from high-temperature compost. Catalase production in this
      strain increased 31 times and reached 57,630U/mL after optimization in a shake
      flask, which might represent the highest catalase activity level among reported
      wild strains. This catalase was further purified and identified. The purified
      enzyme showed a specific activity of 219,360U/mg, higher than many other
      catalases. The molecular weight of this enzyme is 52kDa according to sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the enzyme was
      identified as a monofunctional haeme catalase of Ureibacillus thermosphaericus by
      liquid chromatography-mass spectrometry (LC-MS)/MS. The optimal reaction
      temperature for this catalase was found to be 60 degrees C. Stability was
      observed at 60 degrees C and at a pH of 10.0, indicating the superiority of this
      enzyme at a high temperature and under alkaline conditions. Therefore, this
      catalase is a prospective candidate for industrial production and applications.
      The gene encoding this catalase is 1503bp. As the amino acid sequence shows low
      similarity with other catalases, we suggest that this is a novel monofunctional
      haeme catalase.

PMID- 28501606
TI  - Diabetes present and future.

PMID- 28501605
TI  - The role of multilayers in preventing the premature buckling of the pulmonary
      surfactant.
AB  - The pulmonary surfactant is a protein-lipid mixture that spreads into a film at
      the air-lung interface. The highly-compacted molecules of the film keep the
      interface from shrinking under the influence of otherwise high surface tension
      and thus prevent atelectasis. We have previously shown that for the film to
      withstand a high film pressure without collapsing it needs to assume a specific
      architecture of a molecular monolayer with islands of stacks of molecular
      multilayers scattered over the area. Surface activity was assessed in a captive
      bubble surfactometer (CBS) and the role of cholesterol and oxidation on
      surfactant function examined. The surfactant film was conceptualized as a plate
      under pressure. Finite element analysis was used to evaluate the role of the
      multilayer stacks in preventing buckling of the plate during compression. The
      model of film topography was constructed from atomic force microscope (AFM) scans
      of surfactant films and known physical properties of
      dipalmitoylphosphatidylcholine (DPPC), a major constituent of surfactant, using
      ANSYS structural-analysis software. We report that multilayer structures increase
      film stability. In simulation studies, the critical load required to induce
      surfactant film buckling increased about two-fold in the presence of multilayers.
      Our in vitro surfactant studies showed that surface topography varied between
      functional and dysfunctional films. However, the critical factor for film
      stability was the anchoring of the multilayers. Furthermore, the anchoring of
      multilayers and mechanical stability of the film was dependent on the presence of
      hydrophobic surfactant protein-C. The current study expands our understanding of
      the mechanism of surfactant inactivation in disease.

PMID- 28501607
TI  - The association between high levels of cumulative life stress and aberrant
      resting state EEG dynamics in old age.
AB  - Cumulative experienced stress produces shortcomings in old adults' cognitive
      performance. These are reflected in electrophysiological changes tied to task
      execution. This study explored whether stress-related aberrations in older
      adults' electroencephalographic (EEG) activity were also apparent in the system
      at rest. To this effect, the amount of stressful life events experienced by 60
      young and 60 elderly participants were assessed in conjunction with resting state
      power changes in the delta, theta, alpha, and beta frequencies during a resting
      EEG recording. Findings revealed elevated levels of delta power among elderly
      individuals reporting high levels of cumulative life stress. These differed
      significantly from young high and low stress individuals and old adults with low
      levels of stress. Increases of delta activity have been linked to the emergence
      of conditions such as Alzheimer's Disease and Mild Cognitive Impairment. Thus, a
      potential interpretation of our findings associates large amounts of cumulative
      stress with an increased risk of developing age-related cognitive pathologies in
      later life.

PMID- 28501608
TI  - Porosity of spacer-filled channels in spiral-wound membrane systems:
      Quantification methods and impact on hydraulic characterization.
AB  - The porosity of spacer-filled feed channels influences the hydrodynamics of
      spiral-wound membrane systems and impacts the overall performance of the system.
      Therefore, an exact measurement and a detailed understanding of the impact of the
      feed channel porosity is required to understand and improve the hydrodynamics of
      spiral-wound membrane systems applied for desalination and wastewater reuse. The
      objectives of this study were to assess the accuracy of porosity measurement
      techniques for feed spacers differing in geometry and thickness and the
      consequences of using an inaccurate method on hydrodynamic predictions, which may
      affect permeate production. Six techniques were applied to measure the porosity
      namely, three volumetric techniques based on spacer strand count together with a
      cuboidal (SC), cylindrical (VCC) and ellipsoidal volume calculation (VCE) and
      three independent techniques based on volume displacement (VD), weight and
      density (WD) and computed tomography (CT) scanning. The CT method was introduced
      as an alternative for the other five already existing and applied methods in
      practice. Six feed spacers used for the porosity measurement differed in filament
      thickness, angle between the filaments and mesh-size. The results of the studies
      showed differences between the porosities, measured by the six methods. The
      results of the microscopic techniques SC, VCC and VCE deviated significantly from
      measurements by VD, WD and CT, which showed similar porosity values for all
      spacer types. Depending on the maximum deviation of the porosity measurement
      techniques from -6% to +6%, (i) the linear velocity deviations were -5.6% and
      +6.4% respectively and (ii) the pressure drop deviations were -31% and +43%
      respectively, illustrating the importance of an accurate porosity measurement.
      Because of the accuracy and standard deviation, the VD and WD method should be
      applied for the porosity determination of spacer-filled channels, while the CT
      method is recommended for numerical modelling purposes. The porosity has a linear
      relationship with the flow velocity and a superlinear effect on the pressure
      drop. Accurate porosity data are essential to evaluate feed spacer performance in
      spiral-wound membrane systems. Porosity of spacer-filled feed channels has a
      strong impact on membrane performance and biofouling impact.

PMID- 28501609
TI  - Return on investment from fuel treatments to reduce severe wildfire and erosion
      in a watershed investment program in Colorado.
AB  - A small but growing number of watershed investment programs in the western United
      States focus on wildfire risk reduction to municipal water supplies. This paper
      used return on investment (ROI) analysis to quantify how the amounts and
      placement of fuel treatment interventions would reduce sediment loading to the
      Strontia Springs Reservoir in the Upper South Platte River watershed southwest of
      Denver, Colorado following an extreme fire event. We simulated various extents of
      fuel mitigation activities under two placement strategies: (a) a strategic
      treatment prioritization map and (b) accessibility. Potential fire behavior was
      modeled under each extent and scenario to determine the impact on fire severity,
      and this was used to estimate expected change in post-fire erosion due to
      treatments. We found a positive ROI after large storm events when fire mitigation
      treatments were placed in priority areas with diminishing marginal returns after
      treating >50-80% of the forested area. While our ROI results should not be used
      prescriptively they do show that, conditional on severe fire occurrence and
      precipitation, investments in the Upper South Platte could feasibly lead to
      positive financial returns based on the reduced costs of dredging sediment from
      the reservoir. While our analysis showed positive ROI focusing only on post-fire
      erosion mitigation, it is important to consider multiple benefits in future ROI
      calculations and increase monitoring and evaluation of these benefits of wildfire
      fuel reduction investments for different site conditions and climates.

PMID- 28501610
TI  - Application of doped photocatalysts for organic pollutant degradation - A review.
AB  - Advanced oxidation process involves production of hydroxyl radical for industrial
      wastewater treatment. This method is based on the irradiation of UV light to
      photocatalysts such as TiO2 and ZnO for photodegradation of pollutant. UV light
      is used for irradiation in photocatalytic process because TiO2 has a high band
      gap energy which is around 3.2 eV. There can be shift adsorption to visible light
      by reducing the band gap energy to below 3.2 eV. Doped catalyst is one of the
      means to reduce band gap energy. Different methods are used for doped catalyst
      which uses transition metals and titanium dioxide. The band gap energy of three
      types of transition metals Fe, Cd and Co after being doped with TiO2, are around
      2.88 ev, 2.97ev and 2.96 ev, respectively which are all below TiO2 energy. Some
      of the transition metals change the energy level to below 3.2 eV and the
      adsorption shifts to visible light for degradation of industrial pollutant after
      being doped with titanium dioxide. This paper aims at providing a deep insight
      into advanced oxidation processes, photocatalysts and their applications in
      wastewater treatment, doping processes and the effects of operational factors on
      photocatalytic degradation.

PMID- 28501611
TI  - Multilocus phylogeny and statistical biogeography clarify the evolutionary
      history of major lineages of turtles.
AB  - Despite their complex evolutionary history and the rich fossil record, the higher
      level phylogeny and historical biogeography of living turtles have not been
      investigated in a comprehensive and statistical framework. To tackle these
      issues, we assembled a large molecular dataset, maximizing both taxonomic and
      gene sampling. As different models provide alternative biogeographical scenarios,
      we have explicitly tested such hypotheses in order to reconstruct a robust
      biogeographical history of Testudines. We scanned publicly available databases
      for nucleotide sequences and composed a dataset comprising 13 loci for 294 living
      species of Testudines, which accounts for all living genera and 85% of their
      extant species diversity. Phylogenetic relationships and species divergence times
      were estimated using a thorough evaluation of fossil information as calibration
      priors. We then carried out the analysis of historical biogeography of Testudines
      in a fully statistical framework. Our study recovered the first large-scale
      phylogeny of turtles with well-supported relationships following the topology
      proposed by phylogenomic works. Our dating result consistently indicated that the
      origin of the main clades, Pleurodira and Cryptodira, occurred in the early
      Jurassic. The phylogenetic and historical biogeographical inferences permitted us
      to clarify how geological events affected the evolutionary dynamics of crown
      turtles. For instance, our analyses support the hypothesis that the breakup of
      Pangaea would have driven the divergence between the cryptodiran and pleurodiran
      lineages. The reticulated pattern in the ancestral distribution of the
      cryptodiran lineage suggests a complex biogeographic history for the clade, which
      was supposedly related to the complex paleogeographic history of Laurasia. On the
      other hand, the biogeographical history of Pleurodira indicated a tight
      correlation with the paleogeography of the Gondwanan landmasses.

PMID- 28501612
TI  - The effects of Pleistocene climate change on biotic differentiation in a montane
      songbird clade from Wallacea.
AB  - The role of Pleistocene Ice Age in tropical diversification is poorly understood,
      especially in archipelagos, in which glaciation-induced sea level fluctuations
      may lead to complicated changes in land distribution. To assess how Pleistocene
      land bridges may have facilitated gene flow in tropical archipelagos, we
      investigated patterns of diversification in the rarely-collected rusty-bellied
      fantail Rhipidura teysmanni (Passeriformes: Rhipiduridae) complex from Wallacea
      using a combination of bioacoustic traits and whole-genome sequencing methods (dd
      RADSeq). We report a biogeographic leapfrog pattern in the vocalizations of these
      birds, and uncover deep genomic divergence among island populations despite the
      presence of intermittent land connections between some. We demonstrate how rare
      instances of genetic introgression have affected the evolution of this species
      complex, and document the presence of double introgressive mitochondrial sweeps,
      highlighting the dangers of using only mitochondrial DNA in evolutionary
      research. By applying different tree inference approaches, we demonstrate how
      concatenation methods can give inaccurate results when investigating divergence
      in closely-related taxa. Our study highlights high levels of cryptic avian
      diversity in poorly-explored Wallacea, elucidates complex patterns of Pleistocene
      climate-mediated diversification in an elusive montane songbird, and suggests
      that Pleistocene land bridges may have accounted for limited connectivity among
      montane Wallacean biota.

PMID- 28501613
TI  - Naegleria fowleri infections.

PMID- 28501614
TI  - Shaping mitochondrial dynamics: The role of cAMP signalling.
AB  - In recent years, our idea of mitochondria evolved from "mere" energy and
      metabolite producers to key regulators of many cellular functions. In order to
      preserve and protect their functional status, these organelles engage a number of
      dynamic processes that allow them to decrease accumulated burden and maintain
      their homeostasis. Indeed, mitochondria can unite (fusion), divide (fission),
      position themselves strategically in the cell (motility/trafficking) and if
      irreversibly damaged or dysfunctional eliminated (mitophagy). These dynamic
      processes can be controlled both by mitochondrial and cellular signalling
      pathways, hence allowing mitochondria to tune their function to the cellular
      needs. Among the regulatory mechanisms, reversible phosphorylation downstream the
      cyclic AMP (cAMP) signalling cascade was shown to deeply influence mitochondrial
      dynamics. This review explores the emerging evidence suggesting that cAMP is a
      key player in the orchestration of mitochondrial fusion/fission, motility and
      mitophagy, extending the repertoire of this second messenger, which is now
      recognised as a major regulator of mitochondrial homeostasis.

PMID- 28501615
TI  - The changes in glucose metabolism and cell proliferation in the kidneys of
      polycystic kidney disease mini-pig models.
AB  - The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal
      glucose metabolism is maybe involved in hyper-proliferation of renal cyst
      epithelial cells. Mini-pigs are more similar to humans than rodents and
      therefore, are an ideal large animal model. In this study, for the first time, we
      systematically investigated the changes in glucose metabolism and cell
      proliferation signaling pathways in the kidney tissues of chronic progressive PKD
      mini-pig models created by knock-outing PKD1gene. The results showed that in the
      kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key
      oxidative phosphorylation enzymes Complexes I and IV significantly decreased. The
      activities of mitochondrial respiration chain Complexes I and IV significantly
      decreased; the phosphorylation level of key metabolism-modulating molecule AMP
      activated protein kinase (AMPK) significantly decreased; and the mammalian target
      of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling
      pathway are activated obviously. This study showed that in the kidneys of PKD
      mini-pigs, the level of glycolysis significantly increased, oxidative
      phosphorylation significantly decreased, and cell proliferation signaling
      pathways significantly activated, suggesting that metabolic changes in PKD may
      result in the occurrence and development of PKD through the activation of
      proliferation signaling pathways.

PMID- 28501616
TI  - Identification of phosphorylation sites on beta1-adrenergic receptor in the mouse
      heart.
AB  - beta1-adrenergic receptor (Adrb1) belongs to the superfamily of G-protein-coupled
      receptors (GPCRs) and plays a critical role in the regulation of heart rate and
      myocardial contraction force. GPCRs are phosphorylated at multiple sites to
      regulate distinct signal transduction pathways in different tissues. However,
      little is known about the location and function of distinct phosphorylation sites
      of Adrb1 in vivo. To clarify the mechanisms underlying functional regulation
      associated with Adrb1 phosphorylation in vivo, we aimed to identify Adrb1
      phosphorylation sites in the mouse heart using phosphoproteomics techniques with
      nano-flow liquid chromatography/tandem mass spectrometry (LC-MS/MS). We revealed
      the phosphorylation residues of Adrb1 to be Ser274 and Ser280 in the third
      intracellular loop and Ser412, Ser417, Ser450, Ser451, and Ser462 at the C
      terminus. We also found that phosphorylation at Ser274, Ser280, and Ser462 was
      enhanced in response to stimulation with an Adrb1 agonist. This is the first
      study to identify Adrb1 phosphorylation sites in vivo. These findings will
      provide novel insights into the regulatory mechanisms mediated by Adrb1
      phosphorylation.

PMID- 28501617
TI  - Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein
      by RAPTA complexes and its E3 ubiquitin ligase activity.
AB  - RAPTA compounds, ([Ru(eta6-arene)(PTA)Cl2], PTA = 1,3,5-triaza-7
      phosphaadamantane), have been reported to overcome drug resistance in cisplatin
      resistant cells. However, the exact mechanism of these complexes is still largely
      unexplored. In this study, the interaction of some RAPTA compounds with the N
      terminal fragment of the BRCA1 RING domain protein was investigated. The binding
      of the RAPTA compounds to the BRCA1 protein resulted in a release of Zn2+ ions in
      a dose and time dependent manner, as well as thermal alteration of ruthenated
      BRCA1 proteins. Electron Transfer Dissociation (ETD) fragmentation mass
      spectrometry revealed the preferential binding sites of the RAPTA complexes on
      the BRCA1 zinc finger RING domain at a similar short peptide stretch,
      Cys24Lys25Phe26Cys27Met28Leu29 and Lys35 (residues 44-49 and 55 on full length
      BRCA1). Changes in the conformation and binding constants of ruthenium-BRCA1
      adducts were established, resulting in inactivation of the RING heterodimer
      BRCA1/BARD1-mediated E3 ubiquitin ligase function. These findings could provide
      mechanistic insight into the mode of action of RAPTA complexes for on tested
      BRCA1 model protein.

PMID- 28501618
TI  - Assessing activity of Hepatitis A virus 3C protease using a cyclized luciferase
      based biosensor.
AB  - Hepatitis A is an acute infection caused by Hepatitis A virus (HAV), which is
      widely distributed throughout the world. The HAV 3C cysteine protease (3Cpro), an
      important nonstructural protein, is responsible for most cleavage within the
      viral polyprotein and is critical for the processes of viral replication. Our
      group has previously demonstrated that HAV 3Cpro cleaves human NF-kappaB
      essential modulator (NEMO), a kinase required in interferon signaling. Based on
      this finding, we generated four luciferase-based biosensors containing the NEMO
      sequence (PVLKAQ?ADIYKA) that is cleaved by HAV 3Cpro and/or the Nostoc
      punctiforme DnaE intein, to monitor the activity of HAV 3Cpro in human embryonic
      kidney cells (HEK-293T). Western blotting showed that HAV 3Cpro recognized and
      cleaved the NEMO cleavage sequence incorporated in the four biosensors, whereas
      only one cyclized luciferase-based biosensor (233-DnaE-HAV, 233DH) showed a
      measurable and reliable increase in firefly luciferase activity, with very low
      background, in the presence of HAV 3Cpro. With this biosensor (233DH), we
      monitored HAV 3Cpro activity in HEK-293T cells, and tested it against a
      catalytically deficient mutant HAV 3Cpro and other virus-encoded proteases. The
      results showed that the activity of this luciferase biosensor is specifically
      dependent on HAV 3Cpro. Collectively, our data demonstrate that the luciferase
      biosensor developed here might provide a rapid, sensitive, and efficient
      evaluation of HAV 3Cpro activity, and should extend our better understanding of
      the biological relevance of HAV 3Cpro.

PMID- 28501620
TI  - Molecular characterization of Netrin-1 and APP receptor binding: New leads to
      block the progression of senile plaques in Alzheimer's disease.
AB  - Alzheimer's disease is a growing concern in the context of the increasing
      lifespan of the populations. The work presented here is part of the fight against
      this threat. It supports a therapeutic approach to reduce the incidence of
      Alzheimer's disease, taking advantage of the specific binding of several domains
      of Netrin-1 to the beta-amyloid precursor protein. This basic knowledge shall
      then be used to predict, design or characterize lead compounds that may in turn
      inhibit/delay Alzheimer's disease's progression, extending the therapeutic offer
      of the other leads already being investigated in this line. The present work is
      focused on the interaction of the various portions of APP with the three domains
      of Netrin-1, the so-called LamNT, EGF-like and NTR domains respectively. It
      reveals in detail which portions of APP and Netrin-1 are specifically involved in
      these interactions, using ELISA technique in combination with protein-protein
      binding simulations. So far unsuspected interaction sites located in Netrin-1 EGF
      like and NTR domains open possibilities for new therapeutic approaches in which
      these sites will be specifically targeted.

PMID- 28501619
TI  - A label-free immunoassay for Flavivirus detection by the Reflective Phantom
      Interface technology.
AB  - Flaviviruses are widespread and cause clinically relevant arboviral diseases that
      impact locally and as imported travel-related infections. Direct detection of
      viraemia is limited, being typically undetectable at onset of symptoms.
      Therefore, diagnosis is primarily based on serology, which is complicated by high
      cross-reactivity across different species. The overlapping geographical
      distribution of the vectors in areas with a weak healthcare system, the increase
      of international travel and the similarity of symptoms highlight the need for
      rapid and reliable multi-parametric diagnostic tests in point-of-care formats. To
      this end we developed a bi-parametric serological microarray using recombinant
      NS1 proteins from Tick-borne encephalitis virus and West Nile virus coupled to a
      low-cost, label-free detection device based on the Reflective Phantom Interface
      (RPI) principle. Specific sequential detection of antibodies in solution
      demonstrates the feasibility of the approach for the surveillance and diagnosis
      of Flaviviruses.

PMID- 28501621
TI  - Discovery of a novel prolyl-tRNA synthetase inhibitor and elucidation of its
      binding mode to the ATP site in complex with l-proline.
AB  - Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family
      of enzymes and catalyzes the synthesis of prolyl-tRNAPro using ATP, l-proline,
      and tRNAPro as substrates. An ATP-dependent PRS inhibitor, halofuginone, was
      shown to suppress autoimmune responses, suggesting that the inhibition of PRS is
      a potential therapeutic approach for inflammatory diseases. Although a few PRS
      inhibitors have been derivatized from natural sources or substrate mimetics,
      small-molecule human PRS inhibitors have not been reported. In this study, we
      discovered a novel series of pyrazinamide PRS inhibitors from a compound library
      using pre-transfer editing activity of human PRS enzyme. Steady-state biochemical
      analysis on the inhibitory mode revealed its distinctive characteristics of
      inhibition with proline uncompetition and ATP competition. The binding activity
      of a representative compound was time-dependently potentiated by the presence of
      l-proline with Kd of 0.76 nM. Thermal shift assays demonstrated the stabilization
      of PRS in complex with l-proline and pyrazinamide PRS inhibitors. The binding
      mode of the PRS inhibitor to the ATP site of PRS enzyme was elucidated using the
      ternary complex crystal structure with l-proline. The results demonstrated the
      different inhibitory and binding mode of pyrazinamide PRS inhibitors from
      preceding halofuginone. Furthermore, the PRS inhibitor inhibited intracellular
      protein synthesis via a different mode than halofuginone. In conclusion, we have
      identified a novel drug-like PRS inhibitor with a distinctive binding mode. This
      inhibitor was effective in a cellular context. Thus, the series of PRS inhibitors
      are considered to be applicable to further development with differentiation from
      preceding halofuginone.

PMID- 28501622
TI  - The role of plasmin in the pathogenesis of murine multiple myeloma.
AB  - Aside from a role in clot dissolution, the fibrinolytic factor, plasmin is
      implicated in tumorigenesis. Although abnormalities of coagulation and
      fibrinolysis have been reported in multiple myeloma patients, the biological
      roles of fibrinolytic factors in multiple myeloma (MM) using in vivo models have
      not been elucidated. In this study, we established a murine model of fulminant MM
      with bone marrow and extramedullar engraftment after intravenous injection of B53
      cells. We found that the fibrinolytic factor expression pattern in murine B53 MM
      cells is similar to the expression pattern reported in primary human MM cells.
      Pharmacological targeting of plasmin using the plasmin inhibitors YO-2 did not
      change disease progression in MM cell bearing mice although systemic plasmin
      levels was suppressed. Our findings suggest that although plasmin has been
      suggested to be a driver for disease progression using clinical patient samples
      in MM using mostly in vitro studies, here we demonstrate that suppression of
      plasmin generation or inhibition of plasmin cannot alter MM progression in vivo.

PMID- 28501623
TI  - Efficient direct conversion of human fibroblasts into myogenic lineage induced by
      co-transduction with MYCL and MYOD1.
AB  - The skeletal muscle consists of contractile myofibers and plays essential roles
      for maintenance of body posture, movement, and metabolic regulation. During the
      development and regeneration of the skeletal muscle tissue, the myoblasts fuse
      into multinucleated myotubes that subsequently form myofibers. Transplantation of
      myoblasts may make possible a novel regenerative therapy against defects or
      dysfunction of the skeletal muscle. It is reported that rodent fibroblasts are
      converted into myoblast-like cells and fuse to form syncytium after forced
      expression of exogenous myogenic differentiation 1 (MYOD1) that is a key
      transcription factor for myoblast differentiation. But human fibroblasts are less
      efficiently converted into myoblasts and rarely fused by MYOD1 alone. Here we
      found that transduction of v-myc avian myelocytomatosis viral oncogene lung
      carcinoma derived homolog (MYCL) gene in combination with MYOD1 gene induced
      myoblast-like phenotypes in human fibroblasts more strongly than MYOD1 gene
      alone. The rate of conversion was approximately 90%. The directly converted
      myoblasts (dMBs) underwent fusion in an ERK5 pathway-dependent manner. The dMBs
      also formed myofiber-like structure in vivo after an inoculation into mice at the
      subcutaneous tissue. The present results strongly suggest that the combination of
      MYCL plus MYOD1 may promote direct conversion of human fibroblasts into
      functional myoblasts that could potentially be used for regenerative therapy for
      muscle diseases and congenital muscle defects.

PMID- 28501624
TI  - Autophagy is essential for the differentiation of porcine PSCs into insulin
      producing cells.
AB  - Porcine pancreatic stem cells (PSCs) are seed cells with potential use for
      diabetes treatment. Stem cell differentiation requires strict control of protein
      turnover and lysosomal digestion of organelles. Autophagy is a highly conserved
      process that controls the turnover of organelles and proteins within cells and
      contributes to the balance of cellular components. However, whether autophagy
      plays roles in PSC differentiation remains unknown. In this study, we
      successfully induced porcine PSCs into insulin-producing cells and found that
      autophagy was activated during the second induction stage. Inhibition of
      autophagy in the second stage resulted in reduced differentiational efficiency
      and impaired glucose-stimulated insulin secretion. Moreover, the expression of
      active beta-catenin increased while autophagy was activated but was suppressed
      when autophagy was inhibited. Therefore, autophagy is essential to the formation
      of insulin-producing cells, and the effects of autophagy on differentiation may
      be regulated by canonical Wnt signalling pathway.

PMID- 28501625
TI  - Circular RNAs roll into the regulatory network of plants.
AB  - As a novel class of endogenous non-coding RNAs, circular RNAs (circRNAs) have
      become a new research hotspot in recent years. The wide distribution of circRNAs
      in different plant species has been proven. Furthermore, circRNAs show
      significant tissue-specific expression patterns in plant development and are
      responsive to a variety of biotic and abiotic stresses, indicating that circRNAs
      might have important biological functions in plant development. Here, we
      summarize the current knowledge of plant circRNAs in recent years and discuss
      views and perspectives on the possible regulatory roles of plant circRNAs,
      including the function of miRNA sponges, regulating the expression of their
      parental genes or linear mRNAs, translating into peptides or proteins and
      responses to different stresses. These advances have sculpted a framework of
      plant circRNAs and provide new insights for functional RNA regulation research in
      the future.

PMID- 28501626
TI  - A method for the detection of virus infectivity in single cells and real time:
      Towards an automated fluorescence neutralization test.
AB  - Virus neutralizing antibodies are critical correlates of protection in vaccine
      development and are discriminatory in the plaque reduction neutralization test
      when used for the diagnosis of viral infections. However, neutralization assays
      are time consuming, labor intensive and highly variable, thus limiting their use.
      Advances in automated live imaging of cells opened new possibilities for standard
      virus diagnostic techniques such as neutralization assays. To this end, a
      reporter cell line based on the translocation of the transcription factor IRF3 in
      response to infection is proposed. Image acquisition of signal in a microplate
      format allowed the setup of a rapid, semi-automated and high-throughput
      fluorescent neutralization test. The study is extended to the live imaging of
      IRF3 translocations that could potentially cut the time of analysis to few hours.
      The fluorescent neutralization test is suitable for high-throughput assays and
      expandable to other viruses of global importance such as Zika virus.

PMID- 28501627
TI  - Detection of viromes of RNA viruses using the next generation sequencing
      libraries prepared by three methods.
AB  - Virome (viral megagenomics) detection using next generation sequencing has been
      widely applied in virology, but its methods remain complicated and need
      optimization. In this study, we detected the viromes of RNA viruses of one mock
      sample, one pooled duck feces sample and one pooled mink feces sample on the
      Personal Genome Machine platform using the sequencing libraries prepared by three
      methods. The sequencing primers were added through random hybridization and
      ligation to fragmented viral RNA using a RNA-Seq kit in method 1, through random
      reverse transcription (RT) and polymerase chain reaction (PCR) in method 2 which
      was developed in our laboratory, and through hybridization and ligation to
      fragmented amplicons of random RT-PCR using a single primer in method 3. Although
      the results of these three samples (nine libraries) all showed that more
      classified viral families and genera were identified using methods 2 and 3 than
      using method 1, and more classified viral families and genera were identified
      using method 2 than using method 3, most of the differences were of no
      statistical significance. Moreover, 11 mammalian viral genera in minks were
      possibly identified for the first time through this study.

PMID- 28501628
TI  - Evolutionary expansion and structural functionalism of the ancient family of
      profilin proteins.
AB  - Structure and functional similarities of a recent protein's orthologs with its
      ancient counterpart are largely determined by the configuration of evolutionary
      preservation of amino acids. The emergence of genome sequencing databases allowed
      dissecting the evolutionarily important gene families at a comprehensive and
      genome-wide scale. The profilin multi-gene family is an ancient, universal, and
      functionally diverged across kingdoms, which regulates various aspects of
      cellular development in both prokarya and eukarya, especially cell-wall
      maintenance through actin sequestering, nucleation and cytokinesis. We performed
      a meta-analysis of the evolutionary expansion, structural conservation, evolution
      of function motifs, and transcriptional biases of profilin proteins across
      kingdoms. An exhaustive search of various genome databases of cyanobacteria,
      fungi, animalia and plantae kingdoms revealed 172 paralogous/orthologous
      profilins those were phylogenetically clustered in various groups. Orthologous
      gene comparisons indicated that segmental and tandem duplication events under
      strong purifying selection are predominantly responsible for their convoluted
      structural divergences. Evidently, structural divergences were more prevalent in
      the paralogs than orthologs, and evolutionary variations in the exon/intron
      architecture were accomplished by 'exon/intron-gain' and insertion/deletion
      during sequence-exonization. Remarkably, temporal expression evolution of
      profilin paralogs/homeologs during cotton fiber domestication provides
      evolutionary impressions of the selection of highly diverged transcript abundance
      notably in the fiber morpho-evolution. These results provide global insights into
      the profilin evolution, their structural design across taxa; and their future
      utilization in translational research.

PMID- 28501629
TI  - Statistical support for Sema3A and multiple sclerosis.

PMID- 28501630
TI  - Identification of potential crucial genes associated with steroid-induced
      necrosis of femoral head based on gene expression profile.
AB  - The aim of this study was to explore potential crucial genes associated with the
      steroid-induced necrosis of femoral head (SINFH) and to provide valid biological
      information for further investigation of SINFH. Gene expression profile of
      GSE26316, generated from 3 SINFH rat samples and 3 normal rat samples were
      downloaded from Gene Expression Omnibus (GEO) database. The differentially
      expressed genes (DEGs) were identified using LIMMA package. After functional
      enrichment analyses of DEGs, protein-protein interaction (PPI) network and sub
      PPI network analyses were conducted based on the STRING database and cytoscape.
      In total, 59 up-regulated DEGs and 156 downregulated DEGs were identified. The up
      regulated DEGs were mainly involved in functions about immunity (e.g. Fcer1A and
      Il7R), and the downregulated DEGs were mainly enriched in muscle system process
      (e.g. Tnni2, Mylpf and Myl1). The PPI network of DEGs consisted of 123 nodes and
      300 interactions. Tnni2, Mylpf, and Myl1 were the top 3 outstanding genes based
      on both subgraph centrality and degree centrality evaluation. These three genes
      interacted with each other in the network. Furthermore, the significant network
      module was composed of 22 downregulated genes (e.g. Tnni2, Mylpf and Myl1). These
      genes were mainly enriched in functions like muscle system process. The DEGs
      related to the regulation of immune system process (e.g. Fcer1A and Il7R), and
      DEGs correlated with muscle system process (e.g. Tnni2, Mylpf and Myl1) may be
      closely associated with the progress of SINFH, which is still needed to be
      confirmed by experiments.

PMID- 28501631
TI  - Plasmid transfection in bovine cells: Optimization using a realtime monitoring of
      green fluorescent protein and effect on gene reporter assay.
AB  - Gene reporter technology (GRT) has opened several new avenues for monitoring
      biological events including the activation of transcription factors, which are
      central to the study of nutrigenomics. However, this technology relies heavily on
      the insertion of foreign plasmid DNA into the nuclei of cells (i.e.,
      transfection), which can be very challenging and highly variable among cell
      types. The objective of this study was to investigate the optimal conditions to
      generate reliable GRT assay data on bovine immortalized cell lines, Madin Darby
      Bovine Kidney (MDBK) and bovine mammary epithelial alveolar (MACT) cells. Results
      are reported for two experiments. In Experiment 1, using 96 well-plate and a
      robotic inverted fluorescent microscope, we compared transfection efficiency
      among commercially available transfection reagents (TR) Lipofectamine(r) 3000
      (Lipo3), Lipofectamine(r) LTX (LipoLTX), and TransIT-X2(r) (TransX2), three doses
      of TR (i.e., 0.15, 0.3, and 0.4MUL/well), and three doses of Green Fluorescent
      Protein plasmid DNA (i.e., 10, 25, and 50ng/well). Transfection efficiency and
      mortality rate were analyzed using CellProfiler software. Transfection efficiency
      increased until the end of the experiment (20h post-transfection) at which point
      MACT had greater transfection than MDBK cells (16.3% vs. 2.2%). It is unclear the
      reason for the low transfection in MDBK cells. Maximal transfection efficiency
      was obtained with 0.3MUL/well of LipoLTX plus 25ng/well of plasmid DNA (ca.
      29.5+/-1.9%) and 0.15MUL/well of LipoLTX plus 25ng/well of plasmid DNA (ca. 4.0+/
      0.4%) for MACT and MDBK cells, respectively. The higher amount of TR and DNA was
      generally associated with higher cell mortality. Using high, medium, and low
      transfection efficiency conditions determined in Experiment 1, we performed a GRT
      assay for peroxisome proliferator-activated response element (PPRE) luciferase in
      MACT and MDBK cells treated with 10nM or 100nM of synthetic Peroxisome
      Proliferator-activated Receptor beta/sigma (PPARbeta/sigma) agonist. The GRT
      assay was unaffected by poor transfection in MACT cells although the high
      transfection hampered the possibility of detecting differences between 10 and
      100nM of the PPARbeta/delta agonist. In MDBK cells, low transfection efficiency
      (<2.0%) failed to detect any differences with GRT assay. The level of
      transfection was positively associated with a lower coefficient of variation of
      GRT data. Overall, our data indicates that results of GRT assays are affected by
      transfection efficiency and a minimum transfection of 2% is required. Thus,
      factors such as TR type, TR amount, and DNA plasmid amount need to be optimized
      for a specific cell type before performing GRT assays.

PMID- 28501632
TI  - High levels of maternally transferred mercury disrupt magnetic responses of
      snapping turtle hatchlings (Chelydra serpentina).
AB  - The Earth's magnetic field is involved in spatial behaviours ranging from long
      distance migration to non-goal directed behaviours, such as spontaneous magnetic
      alignment (SMA). Mercury is a harmful pollutant most often generated from
      anthropogenic sources that can bio-accumulate in animal tissue over a lifetime.
      We compared SMA of hatchling snapping turtles from mothers captured at reference
      (i.e., low mercury) and mercury contaminated sites. Reference turtles showed
      radio frequency-dependent SMA along the north-south axis, consistent with
      previous studies of SMA, while turtles with high levels of maternally inherited
      mercury failed to show consistent magnetic alignment. In contrast, there was no
      difference between reference and mercury exposed turtles on standard performance
      measures. The magnetic field plays an important role in animal orientation
      behaviour and may also help to integrate spatial information from a variety of
      sensory modalities. As a consequence, mercury may compromise the performance of
      turtles in a wide variety of spatial tasks. Future research is needed to
      determine the threshold for mercury effects on snapping turtles, whether mercury
      exposure compromises spatial behaviour of adult turtles, and whether mercury has
      a direct effect on the magnetoreception mechanism(s) that mediate SMA or a more
      general effect on the nervous system.

PMID- 28501633
TI  - Atmospheric mercury deposition to forests in the eastern USA.
AB  - Atmospheric mercury (Hg) deposition to forests is important because half of the
      land cover in the eastern USA is forest. Mercury was measured in autumn
      litterfall and weekly precipitation samples at a total of 27 National Atmospheric
      Deposition Program (NADP) monitoring sites in deciduous and mixed deciduous
      coniferous forests in 16 states in the eastern USA during 2007-2014. These
      simultaneous, uniform, repeated, annual measurements of forest Hg include the
      broadest area and longest time frame to date. The autumn litterfall-Hg
      concentrations and litterfall mass at the study sites each year were combined
      with annual precipitation-Hg data. Rates of litterfall-Hg deposition were higher
      than or equal to precipitation-Hg deposition rates in 70% of the annual data,
      which indicates a substantial contribution from litterfall to total atmospheric
      Hg deposition. Annual litterfall-Hg deposition in this study had a median of 11.7
      MUg per square meter per year (MUg/m2/yr) and ranged from 2.2 to 23.4 MUg/m2/yr.
      It closely matched modeled dry-Hg deposition, based on land cover at selected
      NADP Hg-monitoring sites. Mean annual atmospheric-Hg deposition at forest study
      sites exhibited a spatial pattern partly explained by statistical differences
      among five forest-cover types and related to the mapped density of Hg emissions.
      Forest canopies apparently recorded changes in atmospheric-Hg concentrations over
      time because litterfall-Hg concentrations decreased year to year and litterfall
      Hg concentrations were significantly higher in 2007-2009 than in 2012-2014. These
      findings reinforce reported decreases in Hg emissions and atmospheric elemental
      Hg concentrations during this same time period. Methylmercury (MeHg) was detected
      in all litterfall samples at all sites, compared with MeHg detections in less
      than half the precipitation samples at selected sites during the study. These
      results indicate MeHg in litterfall is a pathway into the terrestrial food web
      where it can accumulate in the prey of songbirds, bats, and raptors.

PMID- 28501634
TI  - Helminth infracommunity of the cane toad Rhinella marina (Anura: Bufonidae)
      within its native distribution range.
AB  - During August 2010, a total of 66 cane toad Rhinella marina were collected in
      Laguna de Coyuca, Guerrero, Mexico and examined for the presence of helminths.
      Ninety-two percent were parasitized by 1 or more parasite species. A total of
      4624 individuals were found, belonging to 8 helminth taxa (1 digenean, 1 cestode
      and 6 nematodes). Infracommunities harbored by this host species are highly
      variable (mean Jaccard similarity index 0.31+/-0.27); mean percent similarity
      index 0.26+/-0.32) and depauperate (mean richness 1.91+/-0.92; mean abundance
      64.4+/-100.34); almost 50% of them were dominated by Rhabdias fuelleborni, a skin
      penetrating nematode. Differences related to host gender and size were found,
      since males registered infracommunities with lower species richness and diversity
      than females. The reproductive condition of females (collected during the
      breeding season) might explain the results obtained; during this season, females
      invest less in resistance to infection in favor of investing resources in
      reproduction. However, confirmation of this statement can only be made by
      sampling in the dry season, when the toads do not reach their reproductive peak.

PMID- 28501635
TI  - Determining the role of inflammation in the selection of JAK2 mutant cells in
      myeloproliferative neoplasms.
AB  - Myeloproliferative neoplasm (MPN) is a hematologic malignancy characterized by
      the clonal outgrowth of hematopoietic cells with a somatically acquired mutation
      most commonly in JAK2 (JAK2V617F). This mutation endows upon myeloid progenitors
      cytokine independent growth and consequently leads to excessive production of
      myeloid lineage cells. It has been previously suggested that inflammation may
      play a role in the clonal evolution of JAK2V617F mutants. In particular, it is
      possible that one or more cellular kinetic parameters of hematopoietic stem cells
      (HSCs) are affected by inflammation, such as division or death rates of cells,
      and the probability of HSC differentiation. This suggests a mechanism that can
      steer the outcome of the cellular competition in favor of the mutants, initiating
      the disease. In this paper we create a number of mathematical evolutionary
      models, from very abstract to more concrete, that describe cellular competition
      in the context of inflammation. It is possible to build a model axiomatically,
      where only very general assumptions are imposed on the modeling components and no
      arbitrary (and generally unknown) functional forms are used, and still generate a
      set of testable predictions. In particular, we show that, if HSC death is
      negligible, the evolutionary advantage of mutant cells can only be conferred by
      an increase in differentiation probability of HSCs in the presence of
      inflammation, and if death plays a significant role in the dynamics, an
      additional mechanism may be an increase of HSC's division-to-death ratio in the
      presence of inflammation. Further, we show that in the presence of inflammation,
      the wild type cell population is predicted to shrink under inflammation (even in
      the absence of mutants). Finally, it turns out that if only the differentiation
      probability is affected by the inflammation, then the resulting steady state
      population of wild type cells will contain a relatively smaller percentage of
      HSCs under inflammation. If the division-to-death rate is also affected, then the
      percentage of HSCs under inflammation can either decrease or increase, depending
      on other parameters.

PMID- 28501638
TI  - Nitrogen rich core-shell magnetic mesoporous silica as an effective adsorbent for
      removal of silver nanoparticles from water.
AB  - The production and increasing use of silver nanoparticles (AgNPs) obviously
      results in their release into the environment, leading to a risk to the
      environment due to their toxic effects. Thus, the removal of AgNPs from water is
      highly needed. Here, we demonstrate that nitrogen rich (~10% nitrogen content)
      core-shell magnetic mesoporous silica is a promising adsorbent for the removal of
      AgNPs. For this, the poly(ethylenimine) functionalized core-shell magnetic
      mesoporous silica composites (Fe3O4@SiO2-PEI) were prepared, and characterized by
      TEM, FT-IR, XRD, TG and N2 adsorption-desorption. The removal of AgNPs by
      Fe3O4@SiO2-PEI as a function of contact time, concentration of AgNPs, solution pH
      and ionic strength were studied. The adsorption kinetic data could be described
      by the pseudo-second-order rate model. Both Langmuir and Freundlich models fitted
      the adsorption data well. The adsorption capacity for AgNPs is 909.1mg/g, which
      is 5-181 times higher than that of the previously reported adsorbents for AgNPs.
      Interestingly, the silver adsorbed onto Fe3O4@SiO2-PEI exhibits highly catalytic
      activity for 4-nitropheol (4-NP) reduction with a rate constant of 0.072min-1,
      which is much higher than those by other AgNPs reported before. The silver-loaded
      Fe3O4@SiO2-PEI promises good recyclability for at least five cycles, showing
      great potential in practical applications.

PMID- 28501637
TI  - Serial endosymbiosis or singular event at the origin of eukaryotes?
AB  - 'On the Origin of Mitosing Cells' heralded a new way of seeing cellular
      evolution, with symbiosis at its heart. Lynn Margulis (then Sagan) marshalled an
      impressive array of evidence for endosymbiosis, from cell biology to atmospheric
      chemistry and Earth history. Despite her emphasis on symbiosis, she saw plenty of
      evidence for gradualism in eukaryotic evolution, with multiple origins of mitosis
      and sex, repeated acquisitions of plastids, and putative evolutionary
      intermediates throughout the microbial world. Later on, Margulis maintained her
      view of multiple endosymbioses giving rise to other organelles such as
      hydrogenosomes, in keeping with the polyphyletic assumptions of the serial
      endosymbiosis theory. She stood at the threshold of the phylogenetic era, and
      anticipated its potential. Yet while predicting that the nucleotide sequences of
      genes would enable a detailed reconstruction of eukaryotic evolution, Margulis
      did not, and could not, imagine the radically different story that would
      eventually emerge from comparative genomics. The last eukaryotic common ancestor
      now seems to have been essentially a modern eukaryotic cell that had already
      evolved mitosis, meiotic sex, organelles and endomembrane systems. The long
      search for missing evolutionary intermediates has failed to turn up a single
      example, and those discussed by Margulis turn out to have evolved reductively
      from more complex ancestors. Strikingly, Margulis argued that all eukaryotes had
      mitochondria in her 1967 paper (a conclusion that she later disavowed). But she
      developed her ideas in the context of atmospheric oxygen and aerobic respiration,
      neither of which is consistent with more recent geological and phylogenetic
      findings. Instead, a modern synthesis of genomics and bioenergetics points to the
      endosymbiotic restructuring of eukaryotic genomes in relation to bioenergetic
      membranes as the singular event that permitted the evolution of morphological
      complexity.

PMID- 28501636
TI  - Determining whether observed eukaryotic cell migration indicates chemotactic
      responsiveness or random chemokinetic motion.
AB  - Chemotaxis, the motion of cells directed by a gradient of chemoattractant
      molecules, guides cells in immune response, development, wound healing, and
      cancer. Unfortunately, this process is difficult to distinguish from
      chemokinesis, i.e., stimulated random cell motion. Chemotaxis is frequently
      inferred by determining how many cells cross a boundary in a chemotaxis assay,
      for example how many cells crawl into a chemoattractant-infused filter, or how
      many cells enter a defined region in an under-agarose assay or agarose spot
      assay. To mitigate possible ambiguity in whether motion observed in these assays
      is directed by the chemoattractant gradient or by chemokinesis, we developed a
      mathematical model to determine when such methods indeed indicate directed motion
      of cells. In contrast to previous analyses of chemotaxis assays, we report not
      just the gradients that arise in the assays but also resulting cell motion. We
      applied the model to data obtained from rigorous measurements and show, as
      examples, that MDA-MB-231 breast-cancer cells are at least 20 times less
      sensitive to gradients of EGF or CXCL12 than neutrophils are to formyl peptides;
      we then used this information to determine the extent to which gradient sensing
      increases the rate of boundary crossing relative to a random-motility control.
      Results show, for example, that in the filter assay, 2-4 times as many
      neutrophils pass through the filter when exposed to a gradient as when the
      gradient is absent. However, in the other combinations of cells and assays we
      considered, only 10-20% more cells are counted as having migrated in a directed,
      rather than random, motility condition. We also discuss the design of appropriate
      controls for these assays, which is difficult for the under-agarose and agarose
      spot assays. Moreover, although straightforward to perform with the filter assay,
      reliable controls are often not done. Consequently, we infer that chemotaxis is
      frequently over-reported, especially for cells like MDA-MB-231 cells, which move
      slowly and are relatively insensitive to gradients. Such results provide insights
      into the use of chemotaxis assays, particularly if one wants to acquire and
      analyze quantitative data.

PMID- 28501639
TI  - Comparative evaluation of thermal decomposition behavior and thermal stability of
      powdered ammonium nitrate under different atmosphere conditions.
AB  - In order to analyze the thermal decomposition characteristics of ammonium nitrate
      (AN), its thermal behavior and stability under different conditions are studied,
      including different atmospheres, heating rates and gas flow rates. The evolved
      decomposition gases of AN in air and nitrogen are analyzed with a quadrupole mass
      spectrometer. Thermal stability of AN at different heating rates and gas flow
      rates are studied by differential scanning calorimetry, thermogravimetric
      analysis, paired comparison method and safety parameter evaluation. Experimental
      results show that the major evolved decomposition gases in air are H2O, NH3, N2O,
      NO, NO2 and HNO3, while in nitrogen, H2O, NH3, NO and HNO3 are major components.
      Compared with nitrogen atmosphere, lower initial and end temperatures, higher
      heat flux and broader reaction temperature range are obtained in air. Meanwhile,
      higher air gas flow rate tends to achieve lower reaction temperature and to
      reduce thermal stability of AN. Self-accelerating decomposition temperature of AN
      in air is much lower than that in nitrogen. It is considered that thermostability
      of AN is influenced by atmosphere, heating rate and gas flow rate, thus changes
      of boundary conditions will influence its thermostability, which is helpful to
      its safe production, storage, transportation and utilization.

PMID- 28501640
TI  - Rapid immobilization of simulated radioactive soil waste by microwave sintering.
AB  - A rapid and efficient method is particularly necessary in the timely disposal of
      seriously radioactive contaminated soil. In this paper, a series of simulated
      radioactive soil waste containing different contents of neodymium oxide (3
      25wt.%) has been successfully vitrified by microwave sintering at 1300 degrees C
      for 30min. The microstructures, morphology, element distribution, density and
      chemical durability of as obtained vitrified forms have been analyzed. The
      results show that the amorphous structure, homogeneous element distribution, and
      regular density improvement are well kept, except slight cracks emerge on the
      magnified surface for the 25wt.% Nd2O3-containing sample. Moreover, all the
      vitrified forms exhibit excellent chemical durability, and the leaching rates of
      Nd are kept as ~10-4-10-6g/(m2day) within 42days. This demonstrates a potential
      application of microwave sintering in radioactive contaminated soil disposal.

PMID- 28501641
TI  - Facile preparation of 3D GO/CNCs composite with adsorption performance towards
      [BMIM][Cl] from aqueous solution.
AB  - A novel three-dimensional crumpled graphene oxide/cellulose nanocrystals
      (GO/CNCs) composite was successfully synthesized and firstly used as adsorbent
      for the removal of ionic liquid [BMIM][Cl] from aqueous solution. The 3D crumpled
      structure and abundant oxygen of the functional groups on GO/CNCs composite can
      provide more chance for the sorption of [BMIM][Cl] compared with CNCs and GO,
      respectively. Therefore, a series of batch experiments were carried out to
      evaluate the adsorptive property of 3D GO/CNCs composite towards [BMIM][Cl], such
      as the GO mass content, the pH value and contact time. The results showed that
      pseudo-second-order kinetic model and Eovlich model were well fitted with the
      sorption kinetic. The isotherm adsorption data indicated that it was better
      described by Langmuir model, with the maximum sorption capacity of 0.455mmol/g.
      This work provides a facile method for the preparation of 3D structure adsorbent
      from graphene oxide and cellulose nanocrystals which has high adsorption capacity
      of [BMIM][Cl] in aqueous solution.

PMID- 28501643
TI  - Efficient wastewater treatment and simultaneously electricity production using a
      photocatalytic fuel cell based on the radical chain reactions initiated by dual
      photoelectrodes.
AB  - Efficient conversion of wastewater into clean energy was achieved by applying a
      radical chain reaction strategy in a solar responsive photocatalytic fuel cell
      (PFC) system. The system was constructed with two photoelectrodes where ferrous
      ions were added to enhance the radical reactions for organic pollutants
      degradation from the surface of electrodes to the whole solution system via
      coming into a continuous radical chain reaction. The results indicated that the
      short-circuit current (Jsc) and the power density (JVmax) obtained in the PFC
      system is up to 1.41-1.60 and 1.52-2.02 times larger than those of the PFC
      without ferrous ions. Meanwhile, the degradation rate of refractory organics
      (methyl orange, methylene blue, congo red and tetracycline) increased to 91.98%,
      98.57%, 92.36% and 68.09% from 53.61%, 45.38%, 51.09% and 30.65% respectively
      after 90min operation. The proposed PFC with a radical chain reaction strategy
      provides a more economical and efficient way for energy recovery and wastewater
      treatment and implies a possibility of developing much higher efficient PFC
      system when applying the other electrodes.

PMID- 28501642
TI  - A novel method for photo-oxidative degradation of diatrizoate in water via
      electromagnetic induction electrodeless lamp.
AB  - In this study, an electromagnetic induction electrodeless lamp (EIEL) was first
      introduced into UV advanced oxidation processes (AOPs) for photodegradation of
      Diatrizoate (DTZ), which was the most persistent iodinated X-ray contrast medium
      (ICM), and traditional Hg lamps were taken as references. Direct photolysis rate
      of DTZ under EIEL irradiation was 1.34 times as that under Hg irradiation, but
      the electric energy consumption was 0.87 times. In this sense, the combination of
      EIEL and oxidants (O2, H2O2 and S2O82-(PS)) was further investigated. The
      remarkably increased photodegradation rates were observed in UV/PS system due to
      primary contribution rate of SO4- (62.5%) based on the results of radical
      concentrations and second-order rate constants of DTZ with SO4- and OH. Inorganic
      ions influencing the photodegradation process were investigated. The effect of
      natural organic materials (NOMs) in UV/PS system was studied based on
      contribution ratios of light screening effect and quenching. Transformation
      mechanisms of DTZ in UV/PS system included deiodination, intramolecular
      cyclization, decarboxylation, deacetylation and deamination, which were further
      confirmed by frontier electron density calculations. The study indicated that
      UV/PS with EIEL irradiation has the potential to remove pharmaceuticals in
      contaminated aquatic environments.

PMID- 28501644
TI  - Mechanistic and computational studies of PCB 151 dechlorination by zero valent
      magnesium for field remediation optimization.
AB  - Polychlorinated biphenyls (PCBs) are banned in the U.S. but are persistent in the
      environment; current regulations provide an urgent need to remediate PCBs in a
      cost-effective way. In prior work, a novel method of degradation of PCBs via
      hydrodehalogenation with ball milled zero-valent magnesium and activated carbon
      showed promising results even with water present in the system. In this research,
      a detailed study of the byproducts formed in the dechlorination process for PCB
      151 (used as an example of hexa-chlorinated PCB) and a study of the mechanism
      involved in this reaction via density functional theory (DFT) computations are
      presented. It was demonstrated that these reactions are exothermic and involved
      two transition states, the formation of the ionic transition state being the rate
      limiting step of the reaction. The torsion angle of the PCB congeners was also
      shown to be an extremely important factor to be able to use activated carbon as
      part of the remediation process.

PMID- 28501645
TI  - Targeted sequencing identifies novel variants involved in autosomal recessive
      hereditary hearing loss in Qatari families.
AB  - Hereditary hearing loss is characterized by a very high genetic heterogeneity. In
      the Qatari population the role of GJB2, the worldwide HHL major player, seems to
      be quite limited compared to Caucasian populations. In this study we analysed 18
      Qatari families affected by non-syndromic hearing loss using a targeted
      sequencing approach that allowed us to analyse 81 genes simultaneously. Thanks to
      this approach, 50% of these families (9 out of 18) resulted positive for the
      presence of likely causative alleles in 6 different genes: CDH23, MYO6, GJB6,
      OTOF, TMC1 and OTOA. In particular, 4 novel alleles were detected while the
      remaining ones were already described to be associated to HHL in other ethnic
      groups. Molecular modelling has been used to further investigate the role of
      novel alleles identified in CDH23 and TMC1 genes demonstrating their crucial role
      in Ca2+ binding and therefore possible functional role in proteins. Present study
      showed that an accurate molecular diagnosis based on next generation sequencing
      technologies might largely improve molecular diagnostics outcome leading to
      benefits for both genetic counseling and definition of recurrence risk.

PMID- 28501647
TI  - Application of optical action potentials in human induced pluripotent stem cells
      derived cardiomyocytes to predict drug-induced cardiac arrhythmias.
AB  - INTRODUCTION: Human induced pluripotent stem cell-derived cardiomyocytes (hiPS
      CMs) are emerging as new and human-relevant source in vitro model for cardiac
      safety assessment that allow us to investigate a set of 20 reference drugs for
      predicting cardiac arrhythmogenic liability using optical action potential (oAP)
      assay. METHODS: Here, we describe our examination of the oAP measurement using a
      voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using
      hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were
      digitized at 10kHz and the records subsequently analyzed off-line. Cells were
      exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound)
      that were blinded to the investigating laboratory. Action potential parameters
      were measured, including rise time (Trise) of the optical action potential
      duration (oAPD). RESULTS: Significant effects on oAPD were sensitively detected
      with 11 QT-prolonging drugs, while oAPD shortening was observed with ICa
      antagonists, IKr-activator or ATP-sensitive K+ channel (KATP)-opener.
      Additionally, the assay detected varied effects induced by 6 different sodium
      channel blockers. The detection threshold for these drug effects was at or below
      the published values of free effective therapeutic plasma levels or effective
      concentrations by other studies. DISCUSSION: The results of this blinded study
      indicate that OAP is a sensitive method to accurately detect drug-induced effects
      (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early
      after depolarizations) in hiPS-CMs; therefore, this technique will potentially be
      useful in predicting drug-induced arrhythmogenic liabilities in early de-risking
      within the drug discovery phase.

PMID- 28501646
TI  - Developing a framework for digital objects in the Big Data to Knowledge (BD2K)
      commons: Report from the Commons Framework Pilots workshop.
AB  - The volume and diversity of data in biomedical research have been rapidly
      increasing in recent years. While such data hold significant promise for
      accelerating discovery, their use entails many challenges including: the need for
      adequate computational infrastructure, secure processes for data sharing and
      access, tools that allow researchers to find and integrate diverse datasets, and
      standardized methods of analysis. These are just some elements of a complex
      ecosystem that needs to be built to support the rapid accumulation of these data.
      The NIH Big Data to Knowledge (BD2K) initiative aims to facilitate digitally
      enabled biomedical research. Within the BD2K framework, the Commons initiative is
      intended to establish a virtual environment that will facilitate the use,
      interoperability, and discoverability of shared digital objects used for
      research. The BD2K Commons Framework Pilots Working Group (CFPWG) was established
      to clarify goals and work on pilot projects that address existing gaps toward
      realizing the vision of the BD2K Commons. This report reviews highlights from a
      two-day meeting involving the BD2K CFPWG to provide insights on trends and
      considerations in advancing Big Data science for biomedical research in the
      United States.

PMID- 28501648
TI  - Tetrahydroacridine derivatives with fluorobenzoic acid moiety as multifunctional
      agents for Alzheimer's disease treatment.
AB  - A novel series of 9-amino-1,2,3,4-tetrahydroacridine derivatives with 2
      fluorobenzoic acid or 3-fluorobenzoic acid moiety were designed, synthesized and
      evaluated as inhibitors of cholinesterases and aggregation of beta-amyloid. In
      the study target compounds were very potent inhibitors of AChE and BChE. The most
      promising agents had higher inhibitory potency than the reference drugs which was
      tacrine. Ultimately, the kinetic assay shows the most active target compound 3c
      against AChE. Almost all of them were more potent against BChE than AChE.
      Compound 3c in various concentrations was tested by aggregation experiment.
      Inhibition of beta-amyloid aggregation was 77.32% and 80.43% at 50uM and 100uM,
      respectively. Therefore, compound 3c is a promising agent for the treatment of
      AD.

PMID- 28501649
TI  - Different activation of monocyte-derived macrophages by antimicrobial peptides at
      a titanium tibial implantation in rabbits.
AB  - The aim of our study was to assess the functional and morphological features of
      monocyte derived Mfs from rabbits with titanium (Ti) tibial implants, their
      ability to polarize towards M1 or M2 and their reactivity after stimulation with
      neutrophil antimicrobial peptides extract (AMP). The study was conducted on six
      White New Zealand rabbits with tibial implants of pure titanium Grade 2. Blood
      was taken before implantation and 14days after biomaterial implantation. Then,
      blood-derived Mfs were cultured and their function was assessed on the basis of
      morphological changes, generation of nitric oxide (NO), superoxide, and proteases
      release after treatment with LPS or dexamethasone (Dex). As a result of
      polarization we specified two subpopulations of Mfs with features characteristic
      of each subtype. M1 stimulated with LPS exhibited an increased NO and superoxide
      level, and M2 stimulated with Dex which showed higher arginase and lower free
      radical generation. Addition of AMP evoked further changes in Mfs morphology and
      function. After 24h stimulation with AMP an increase of NO was observed in all
      cultures, whereas after 48h it decreased. Production of superoxide lowered,
      especially after 48h, when M1 generated 6.00+/-0.2nM and M1/AMP culture generated
      5.2+/-0.1nM of superoxide. Our study revealed that activated Mfs stimulated with
      AMP demonstrated both pro- and anti-inflammatory features. Moreover, we did not
      detect significant differences between the response of Mfs cultured from blood
      derived monocytes before and after implantation of Ti implants.

PMID- 28501650
TI  - PROBer Provides a General Toolkit for Analyzing Sequencing-Based Toeprinting
      Assays.
AB  - A number of sequencing-based transcriptase drop-off assays have recently been
      developed to probe post-transcriptional dynamics of RNA-protein interaction, RNA
      structure, and RNA modification. Although these assays survey a diverse set of
      epitranscriptomic marks, we use the term toeprinting assays since they share
      methodological similarities. Their interpretation is predicated on addressing a
      similar computational challenge: how to learn isoform-specific chemical
      modification profiles in the face of complex read multi-mapping. We introduce
      PROBer, a statistical model and associated software, that addresses this
      challenge for the analysis of toeprinting assays. PROBer takes sequencing data as
      input and outputs estimated transcript abundances and isoform-specific
      modification profiles. Results on both simulated and biological data demonstrate
      that PROBer significantly outperforms individual methods tailored for specific
      toeprinting assays. Since the space of toeprinting assays is ever expanding and
      these assays are likely to be performed and analyzed together, we believe
      PROBer's unified data analysis solution will be valuable to the RNA community.

PMID- 28501651
TI  - Severity of traumatic injuries predicting psychological outcomes: A surprising
      lack of empirical evidence.
AB  - Despite widespread beliefs that trauma severity is related to levels of
      posttraumatic stress symptoms (PTSS), the empirical evidence to support such
      beliefs is lacking. In the current study we examined Injury Severity Score (ISS),
      a medical measure of event severity for physical injuries, in a sample of 460
      patients admitted to a Level 1 Trauma Center. Results revealed no significant
      relationship between ISS and PTSS, depression, pain, and general physical and
      mental health at baseline, three months, and six months post-injury. However, at
      12 months post-injury, ISS significantly predicted depression, pain, and physical
      health, but was unrelated to PTSS. The effect sizes of these relationships were
      small and would not remain significant if any adjustments for multiple
      comparisons were employed. We conclude that the relationship between ISS and PTSS
      is, at best, weak and inconsistent. The results are discussed in the broader
      picture of event severity and psychological outcomes.

PMID- 28501652
TI  - A new adenovector system for implementing thymulin gene therapy for inflammatory
      disorders.
AB  - Thymulin is a thymic peptide possessing anti-inflammatory effects. In order to
      manipulate thymulin expression in gene therapy studies, we built a bidirectional
      regulatable two-vector Tet-Off system and the corresponding control system. The
      experimental two-vector system, ETV, consists of a recombinant adenovector (RAd)
      harboring an expression cassette centered on a Tet-Off bidirectional promoter
      flanked by a synthetic gene for thymulin and the gene for humanized Green
      Fluorescent Protein (hGFP). The second adenovector of this system, RAd-tTA,
      constitutively expresses the regulatory protein tTA. When cells are co-transduced
      by the two adenovector components, tTA activates the bidirectional promoter and
      both transgenes are expressed. In the presence of the antibiotic doxycycline
      (DOX) transgene expression is deactivated. The control two-vector system, termed
      CTV, is similar to ETV but only expresses hGFP. In CHO-K1, BHK, and C2C12 cells,
      ETV and CTV induced a dose-dependent hGFP expression. In CHO-K1 cells, transgene
      expression was almost completely inhibited by DOX (1mg/ml). After
      intracerebroventricular injection of ETV in rats, thymulin levels increased
      significantly in the cerebrospinal fluid and there was high hGFP expression in
      the ependymal cell layer. When injected intramuscularly the ETV system induced a
      progressive increase in serum thymulin levels, which were inhibited when DOX was
      added to the drinking water. We conclude that our regulatable two-adenovector
      system is an effective molecular tool for implementing short and long-term anti
      inflammatory thymulin gene therapy in animal models of acute or chronic
      inflammation.

PMID- 28501653
TI  - Incorporating wind availability into land use regression modelling of air quality
      in mountainous high-density urban environment.
AB  - Urban air quality serves as an important function of the quality of urban life.
      Land use regression (LUR) modelling of air quality is essential for conducting
      health impacts assessment but more challenging in mountainous high-density urban
      scenario due to the complexities of the urban environment. In this study, a total
      of 21 LUR models are developed for seven kinds of air pollutants (gaseous air
      pollutants CO, NO2, NOx, O3, SO2 and particulate air pollutants PM2.5, PM10) with
      reference to three different time periods (summertime, wintertime and annual
      average of 5-year long-term hourly monitoring data from local air quality
      monitoring network) in Hong Kong. Under the mountainous high-density urban
      scenario, we improved the traditional LUR modelling method by incorporating wind
      availability information into LUR modelling based on surface geomorphometrical
      analysis. As a result, 269 independent variables were examined to develop the LUR
      models by using the "ADDRESS" independent variable selection method and stepwise
      multiple linear regression (MLR). Cross validation has been performed for each
      resultant model. The results show that wind-related variables are included in
      most of the resultant models as statistically significant independent variables.
      Compared with the traditional method, a maximum increase of 20% was achieved in
      the prediction performance of annual averaged NO2 concentration level by
      incorporating wind-related variables into LUR model development.

PMID- 28501655
TI  - Changes of auditory event-related potentials in ovariectomized rats injected with
      d-galactose: Protective role of rosmarinic acid.
AB  - Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful
      agent for protecting central nervous system against age related alterations. In
      this context, the purpose of the present study was to investigate possible
      protective effects of RA on mismatch negativity (MMN) component of auditory event
      related potentials (AERPs) as an indicator of auditory discrimination and echoic
      memory in the ovariectomized (OVX) rats injected with d-galactose combined with
      neurochemical and histological analyses. Ninety female Wistar rats were randomly
      divided into six groups: sham control (S); RA-treated (R); OVX (O); OVX+RA
      treated (OR); OVX+d-galactose-treated (OD); OVX+d-galactose+RA-treated (ODR).
      Eight weeks later, MMN responses were recorded using the oddball condition. An
      amplitude reduction of some components of AERPs was observed due to ovariectomy
      with or without d-galactose administiration and these reduction patterns were
      diverse for different electrode locations. MMN amplitudes were significantly
      lower over temporal and right frontal locations in the O and OD groups versus the
      S and R groups, which was accompanied by increased thiobarbituric acid reactive
      substances (TBARS) and hydroxy-2-nonenal (4-HNE) levels. RA treatment
      significantly increased AERP/MMN amplitudes and lowered the TBARS/4-HNE levels in
      the OR and ODR groups versus the O and OD groups, respectively. Our findings
      support the potential benefit of RA in the prevention of auditory distortion
      related to the estrogen deficiency and d-galactose administration at least partly
      by antioxidant actions.

PMID- 28501654
TI  - Urinary organophosphate insecticide metabolite concentrations during pregnancy
      and children's interpersonal, communication, repetitive, and stereotypic
      behaviors at 8 years of age: The home study.
AB  - BACKGROUND: Prenatal exposure to organophosphate insecticides may be associated
      with autism spectrum disorders and related behaviors. This association may be
      modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme.
      OBJECTIVE: We examined the relationship of prenatal organophosphate insecticide
      biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8
      year old children, and modification of this relationship by child PON1
      polymorphisms. METHODS: Among 224 pregnant women, we quantified concentrations of
      six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate
      insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When
      children were eight years old, we administered the Social Responsiveness Scale
      (SRS), a continuous measure of various dimensions of interpersonal behavior,
      communication, and repetitive/stereotypic behaviors. We estimated the association
      between a 10-fold increase in the sum of six DAP concentrations (SigmaDAP) and
      SRS scores. We examined whether child PON1192 and PON1-108 genotypes modified
      this association. RESULTS: After covariate adjustment, SigmaDAP concentrations
      were not associated with SRS scores [beta=-1.2; 95% confidence interval (CI): 
      4.0, 1.6]. Among children with the PON1-108TT genotype, SigmaDAP concentrations
      were associated with 2.5-point higher (95% CI: -4.9, 9.8) SRS scores; however,
      the association was not different from the 1.8-point decrease (95% CI: -5.8, 2.2)
      among children with PON1-108CT/CC genotypes (SigmaDAP * PON1-108 p-value =0.54).
      The association between SigmaDAP concentrations and SRS scores was not modified
      by PON1192 (SigmaDAP * PON1192 p-value =0.89). CONCLUSIONS: In this cohort,
      prenatal urinary DAP concentrations were not associated with children's social
      behaviors; these associations were not modified by child PON1 genotype.

PMID- 28501656
TI  - Perioperative Outcomes of Open versus Endovascular Repair for Ruptured
      Thoracoabdominal Aneurysms.
AB  - BACKGROUND: Open aneurysm repair (OAR) remains the gold standard for treating
      ruptured thoracoabdominal aortic aneurysms (TAAAs). The aim of our study is to
      compare the 30-day postoperative outcomes among patients with ruptured TAAA
      undergoing OAR versus endovascular aneurysm repair. METHODS: Using the National
      Surgical Quality Improvement Program database (2006-2015), we identified patients
      who underwent OAR and endovascular repair for a ruptured TAAA. Postoperative
      outcomes of interest included mortality, renal failure, stroke, and
      cardiopulmonary complications. The independent impact of repair type on each of
      the aforementioned outcomes was examined after robust risk adjustment. RESULTS: A
      total of 206 ruptured TAAA repairs were performed [OAR 144 (70%) versus
      endovascular 62 (30%)]. The majority of patients were male (53 %) and white
      (77%). The comorbidities were similar between the 2 groups. On average, the
      operative time of OAR was approximately 3 hr longer than endovascular repair (P <
      0.001). The mortality was similar between the 2 groups (OAR 38% versus
      endovascular 26%, P = 0.09). Compared with endovascular repair, OAR was
      associated with higher rates of renal and pulmonary complications (32% vs. 13%, P
      = 0.004; 58% vs. 37%, P = 0.007, respectively). After adjusting for high-risk
      patient characteristics, endovascular repair, in comparison with OAR, was
      associated with a 66% reduction of pulmonary injury and 70% reduction in renal
      failure (odds ratio [OR] 0.34, 95% CI 0.16-0.73, P = 0.005; OR 0.30, 95% CI 0.11
      0.82, P = 0.02). CONCLUSIONS: Our study reflects the contemporary outcomes
      following the repair of ruptured TAAA. Despite similar mortality, the
      endovascular approach was associated with a significant reduction in the risk of
      renal failure and pulmonary injury.

PMID- 28501657
TI  - Effects of Mentorship on Graduating Vascular Surgery Trainees.
AB  - BACKGROUND: Mentorship within surgery, particularly vascular surgery, has not
      been extensively evaluated. This study sought to examine mentorship experiences
      in graduating vascular trainees (VTs). METHODS: An anonymous electronic survey
      examining current mentor relationships, ideal characteristics, academic
      productivity, and operative comfort level was emailed to all US graduating 2015
      (n = 141) and 2016 (n = 144) VTs during their last year of training. A parallel
      survey was emailed to program/associate program directors (PDs) of all US
      vascular training programs (n = 169). RESULTS: Surveys were completed by 65 (38%)
      PDs and 62 (22%) VTs. Forty-three (69%) VTs identified a mentor with no
      difference in frequency of having a mentor noted among gender, type of training
      (fellowship/residency), or geographical region. The majority (41/43, 95%)
      recognized a vascular surgeon as their mentor; the mentor was assigned to 10 of
      43 (23%) trainees and was their PD to 9 of 43 (21%). Ideal mentor
      characteristics, identified by VTs using 4-point Likert scales, were
      approachability, supportiveness, and accessibility (3.94, 3.76, and 3.74,
      respectively), while those of a good mentee were enthusiasm, ethical work, and
      commitment (3.79, 3.69, and 3.45, respectively). Trainees scored accessibility,
      approachability, compassion, and same gender significantly higher than PDs as
      characteristics of ideal mentors (P < 0.05). The majority of PDs thought
      mentorship increased access to research opportunities, professional networking,
      and job opportunities, but not operative skill (90%, 95%, 65%, and 18%,
      respectively). There was no difference between trainees with mentors and those
      without in terms of reported academic productivity or operative comfort level.
      Vascular fellows reported higher comfort than residents in open abdominal aortic
      aneurysm repair (3.32 vs. 2.73, P = 0.006), juxtarenal aneurysm repair (2.8 vs.
      2.1, P = 0.02), and aorto-mesenteric bypass (2.57 vs. 1.93, P = 0.03), and
      neither group was comfortable performing carotid stenting or fenestrated
      endovascular aneurysm repairs. CONCLUSIONS: There is no difference in academic
      productivity or case comfort level between surgical trainees with mentors and
      those without. Possible benefits identified by PDs and trainees include
      professional networking and increased research and job opportunities. Mentors
      should be approachable, accessible, supportive, and ethical, while mentees should
      be enthusiastic, ethical, committed, and approachable. Vascular fellows feel more
      comfortable with open vascular operations than residents, and nether group feels
      comfortable with complex endovascular cases. More research is warranted.

PMID- 28501658
TI  - Hybridizing the "Sandwich" and "Chimney" Techniques in the Endovascular Repair of
      Coarctation of the Aortic Arch and Postcoarctation Ectasia Concomitant with a
      Left Subclavian Artery Aneurysm.
AB  - Coarctation of aorta is a rare congenital malformation and is usually accompanied
      by other cardiac or vascular lesions. In this case, we describe a 51-year-old
      patient who presented with coarctation of the aortic arch and postcoarctation
      ectasia concomitant with a left subclavian artery aneurysm. Endovascular therapy
      included the deployment of an inverted wedge-shaped covered stent inserted by a
      long "chimney" stent and another cylinder-covered stent, forming a "sandwich"
      like configuration. The symptoms were alleviated after surgery, and no
      perioperative or stent-graft-related complications were observed at a 2-year
      follow-up.

PMID- 28501659
TI  - Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector
      Row Computed Tomography Device.
AB  - BACKGROUND: Understanding the difference of Adamkiewicz artery (AKA) presentation
      in healthy and diseased subjects, and the influence of atherosclerotic factors
      prevalent in aortic disease patients, are important for aortic disease
      therapeutic planning. This study used a 320-detector row computed tomography (CT)
      device to examine the impact of clinical aspects of AKA identification in
      individuals with and without aortic disease. METHODS: Angio-CTs obtained from 115
      patients were assessed and the individuals grouped according to the presence or
      absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA
      was identified by three-dimensional multiplanar reconstruction. RESULTS: The
      group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women,
      with a mean age of 53.7 +/- 16.8 years. The group with aortic disease (Group B)
      comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 +/- 11.6 years.
      AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%)
      individuals of Group B (P <= 0.0001). In 53 cases (73.6%), AKA originated on the
      left side. AKA was mainly detected on the left side (73.6%), at the level of T10
      to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had
      increased odds of having undetected AKA. CONCLUSIONS: Using the method described
      and a state of the art 320-detector row CT device, AKA was detected more
      frequently among individuals without aortic disease. Thus, aortic disease and
      atherosclerotic risk factors hindered AKA detection.

PMID- 28501660
TI  - Alcohol Consumption, High-Density Lipoprotein Cholesterol, Antithrombin III, and
      Body Mass Index Are Associated with Great Saphenous Vein Reflux in the Thigh.
AB  - BACKGROUND: Venous valvular reflux is the main cause of chronic venous
      dysfunction. However, the etiology of valvular reflux is not completely
      understood. We conducted this study to investigate new risk factors for venous
      reflux of the great saphenous vein (GSV) in the thigh. METHODS: We studied 139
      consecutive patients (278 legs) who underwent Doppler ultrasonography at our
      hospital between March 2015 and February 2016 for leg discomfort with visible
      varicosities, edema, skin changes, or venous ulcer in the legs. Continuous
      variables included age, body mass index (BMI), hematological and blood chemistry
      parameters, smoking (pack-years), and alcohol consumption (days). Nominal
      variables included sex, comorbidities, smoking status, alcohol drinking status,
      and specific antibodies. The relationship of GSV reflux with pregnancy and number
      of children was investigated in 184 legs of 92 patients among 96 female patients.
      RESULTS: On logistic regression analysis, independent factors determining GSV
      reflux were BMI (B = 0.126, P = 0.012), high-density lipoprotein (HDL)
      cholesterol level (B = 0.029, P = 0.025), duration of alcohol consumption (B =
      1.237 E-4, P = 0.016), and antithrombin III level (B = -0.036, P = 0.011).
      CONCLUSIONS: In this study, the factors determining GSV reflux were higher HDL
      cholesterol level, longer duration of alcohol consumption, lower antithrombin III
      level, and higher BMI.

PMID- 28501661
TI  - Extensive Cerebrovascular and Visceral Artery Dissection and Pseudoaneurysm with
      Underlying Segmental Arterial Mediolysis.
AB  - Segmental arterial mediolysis (SAM) is a nonatherosclerotic, nonhereditary
      vasculopathy that most commonly involves abdominal aortic branches and
      predominantly affects middle-age and elderly populations. Lysis of the outer
      arterial media results in separation of the media from the adventitia leading to
      dissecting aneurysms and/or pseudoaneurysms. We report a unique case of a 47-year
      old man who presented with bilateral internal carotid artery dissection followed
      by dissections and aneurysms involving multiple visceral arteries. This case
      highlights the dramatic manifestation of SAM and discusses the complexity of
      decision-making related to this disease including differential diagnoses and
      management.

PMID- 28501662
TI  - Surgically Treated Pelvic Pain Caused by Nutcracker Syndrome and Worsened by
      Cockett Syndrome in a Child.
AB  - Nutcracker syndrome is rarely seen in the young. Most of the symptoms regress
      during follow-up. Rarely surgical intervention is necessary. This case
      presentation is unique for being the first case of nutcracker syndrome and
      coexistent Cockett syndrome that is treated with surgical intervention.

PMID- 28501663
TI  - Underutilization of Routine Ultrasound Surveillance after Endovascular Aortic
      Aneurysm Repair.
AB  - BACKGROUND: Since 2009, the Society for Vascular Surgery has advocated annual
      surveillance imaging with ultrasound (US) after the first postoperative year for
      uncomplicated endovascular aneurysm repairs (EVARs). We sought to describe
      diffusion of US into long-term routine surveillance and to estimate potential
      cost savings among Medicare beneficiaries after EVAR. METHODS: Using Medicare
      claims data, we identified patients receiving EVAR from 2002 to 2010 and included
      only those who did not subsequently have reinterventions, late aneurysm-related
      complications, or death. We collected all relevant postoperative imaging
      (computed tomography [CT] and US) through 2011. Patients with follow-up less than
      1 year were excluded. We estimated cost savings with increased use of US after
      the first postoperative year. RESULTS: The cohort comprised 24,615 patients with
      a mean follow-up of 3.9 +/- 2.3 years. Mean number of images decreased from 2.23
      in the first postoperative year to 0.31 in the 10th year. Utilization of US at
      the first postoperative year remained low but increased from 15.2% in 2003 to
      28.8% in 2011 (P < 0.001). By the 10th postoperative year, the proportion of
      patients receiving US increased from 8.2% to 37.8%, while use of CT only remained
      high but decreased from 60.8% to 42.1%. Mean cost of surveillance imaging was
      $2,132/CT and $234/US. Performing US in 50-75% of patients beginning 1 year after
      EVAR would decrease costs by 14-48%/year. This translates to a mean cost savings
      of $338-$1135 per imaged patient per year, with an estimated savings to Medicare
      of $155 million to $305 million over 10 years. CONCLUSIONS: CT remains the
      primary modality of surveillance for up to 10 years after EVAR for patients
      without reinterventions or aneurysm-related complications. Increasing the use of
      US and decreasing the use of CT would save cost without compromising outcomes.

PMID- 28501664
TI  - Systemic Thrombolytic Therapy and Catheter-Directed Fragmentation with Local
      Thrombolytic Therapy in Patients with Pulmonary Embolism.
AB  - BACKGROUND: The objective was to compare immediate and long-term results of
      systemic thrombolytic therapy (STT) and catheter-directed fragmentation (CDF)
      with local thrombolytic therapy (LTT) in patients with massive pulmonary embolism
      (PE). METHODS: About 209 patients with massive PE (the high risk of early death)
      were included in our study. From 2008 till 2010 in the first group (n = 102), STT
      was performed. From 2011 till 2013 in the second group (n = 107), CDF with LTT
      was carried out. Echocardiography and pulmonary arteriography were performed in
      all patients on admission to hospital and in 5 days after treatment. The patients
      of both groups were re-examined in 6 months, 1, 2, and 3 years after the
      operation. RESULTS: In the first group, there were 5 (4.9%) cases of in-hospital
      30-day mortality. In the second group, there was 1 (0.9%) case of in-hospital 30
      day mortality (P = 0.08). In the first group, a clinically significant bleeding
      was noted in 4 (3.9%) cases, but it caused mortality only in 1 case. In the
      second group, the clinically significant bleeding was not found (P = 0.038).
      Persistent postembolic pulmonary hypertension (PPPH) in 9.8% cases of patients in
      the first group and 2.9% cases of patients in the second group was determined (P
      = 0.048). CONCLUSIONS: CDF combined with LTT is an effective minimal invasive
      treatment (helped us to reduce significantly the number of bleeding and PPPH
      cases), at least in the midterm, in patients with massive PE.

PMID- 28501665
TI  - A Dedicated Surveillance Program Improves Compliance with Endovascular Aortic
      Aneurysm Repair Follow-up.
AB  - BACKGROUND: Current recommendations suggest lifetime follow-up for endovascular
      aortic aneurysm repair (EVAR) patients to avoid consequences associated with
      endoleak and aneurysm enlargement. Follow-up compliance has been reported between
      43% and 92%, with most single-center studies citing successful follow-up
      surveillance at less than 60%. We investigated follow-up completeness with a
      defined surveillance program and subsequent secondary intervention prevalence
      from a single center. METHODS: Our surveillance program notified patients of the
      need for follow-up imaging and surgeon review. Data were obtained from
      retrospective review of a prospective database, including operative and follow-up
      details, follow-up imaging completeness, endoleak incidence, and secondary
      intervention prevalence. RESULTS: Five hundred seventeen patients received
      elective EVAR from 2005 to 2015. Surveillance was achieved in 425 (82.3%). Mean
      number of follow-up studies was 4.2 +/- 2.9 and median time to first follow-up
      was 36 days. Four hundred forty-eight patients (86.7%) had freedom from
      intervention. Sixty-nine unique patients (13.3%) had 107 secondary interventions.
      Median time to first secondary intervention in 69 patients was 476 days. Mean
      number of imaging studies for secondary intervention patients was 6.1 +/- 3.9,
      compared with mean 3.4 +/- 2.3 for patients without (P < 0.001). Overall
      mortality was 24.6% (n = 127), including 32 deaths of unknown cause (6.2%
      overall) and 95 of non-EVAR-related causes (18.3%). No aneurysm-related deaths
      were reported. CONCLUSIONS: Regular post-EVAR surveillance through a dedicated
      program resulted in a high rate of follow-up compliance, 13.3% rate of secondary
      intervention, and low aneurysm-related mortality. Careful lifetime surveillance
      remains important in long-term care following elective EVAR.

PMID- 28501666
TI  - An Unexpectedly High Rate of Thrombophilia Disorders in Patients with Superficial
      Vein Thrombosis of the Lower Extremities.
AB  - BACKGROUND: Superficial vein thrombosis (SVT) is a common venous condition.
      Recent studies have shown that SVT is associated with high frequency of
      thromboembolic complications: from 22-37% for deep venous thrombosis and up to
      33% for pulmonary embolism. Our goal was to assess the prevalence of major
      hereditary and acquired thrombophilic factors in patients with SVT. METHODS:
      Sixty-six patients presenting with primary SVT underwent evaluation for
      thrombophilia: molecular testing for the factor V Leiden and factor II G20210 A
      (prothrombin) mutations, protein C, protein S, antithrombin deficiency, presence
      of lupus anticoagulant, as well as anticardiolipin antibody titers. Patients aged
      less than 18 years, with confirmed deep vein thrombosis, and pregnant women were
      excluded. RESULTS: 95.5% were Caucasian, and 62.1% were female gender. Age ranged
      from 21-88 years. Molecular testing showed that 34.2% of patients were
      heterozygous for factor V Leiden, 23.6% were heterozygous for the factor II
      mutation, 7.8% had antithrombin deficiency, 2.6% had protein S deficiency, and
      2.1% had protein C deficiency. CONCLUSIONS: Our study showed that hereditary and
      acquired thrombophilias are higher than previously expected and reported.

PMID- 28501667
TI  - Update and new insights in encephalitis.
AB  - Infectious encephalitis is a rare but severe medical condition resulting from
      direct invasion of the brain by viruses, bacteria, fungi or parasites, or
      indirect post-infectious immune or inflammatory disorders when the infectious
      agent does not cross the blood-brain barrier. Infectious encephalitis cases
      represent an interesting and accurate sentinel to follow up on trends in
      infectious diseases or to detect emerging infections. Using Pubmed and Embase, we
      searched the most relevant publications over the last years. We present here an
      update on the important findings and new data recently published about infectious
      encephalitis.

PMID- 28501668
TI  - Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel
      method to compare strategies to optimize antibiotic use.
AB  - OBJECTIVES: The Response Adjusted for Days of Antibiotic Risk (RADAR) statistic
      was proposed to improve the efficiency of trials comparing antibiotic stewardship
      strategies to optimize antibiotic use. We studied the behaviour of RADAR in a non
      inferiority trial in which a beta-lactam monotherapy strategy (n = 656) was non
      inferior to fluoroquinolone monotherapy (n = 888) for patients with moderately
      severe community-acquired pneumonia. METHODS: Patients were ranked according to
      clinical outcome, using five or eight categories, and antibiotic use. RADAR was
      calculated as the probability that the beta-lactam group had a more favourable
      ranking than the fluoroquinolone group. To investigate the sensitivity of RADAR
      to detrimental clinical outcome we simulated increasing rates of 90-day mortality
      in the beta-lactam group and performed the RADAR and non-inferiority analysis.
      RESULTS: The RADAR of the beta-lactam group compared with the fluoroquinolone
      group was 60.3% (95% CI 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%)
      using eight clinical outcome categories, all in favour of beta-lactam. Sample
      sizes for RADAR were 38% (250/653) and 89% (580/653) of the non-inferiority
      sample size calculation, using five or eight clinical outcome categories,
      respectively. With simulated mortality rates, loss of non-inferiority of the beta
      lactam group occurred at a relative risk of 1.125 in the conventional analysis,
      whereas using RADAR the beta-lactam group lost superiority at a relative risk of
      mortality of 1.25 and 1.5, with eight and five clinical outcome categories,
      respectively. CONCLUSIONS: RADAR favoured beta-lactam over fluoroquinolone
      therapy for community-acquired pneumonia. Although RADAR required fewer patients
      than conventional non-inferiority analysis, the statistic was less sensitive to
      detrimental outcomes.

PMID- 28501669
TI  - An update on bacterial brain abscess in immunocompetent patients.
AB  - BACKGROUND: A brain abscess is a focal infection of the brain that begins as a
      localized area of cerebritis. In immunocompetent patients, bacteria are
      responsible for >95% of brain abscesses, and enter the brain either through
      contiguous spread following otitis, sinusitis, neurosurgery, or cranial trauma,
      or through haematogenous dissemination. AIMS: To identify recent advances in the
      field. SOURCES: We searched Medline and Embase for articles published during
      years 2012-2016, with the keywords 'brain' and 'abscess'. CONTENT: The triad of
      headache, fever and focal neurological deficit is complete in ~20% of patients on
      admission. Brain imaging with contrast-preferentially magnetic resonance imaging
      is the reference standard for diagnosis, and should be followed by stereotactic
      aspiration of at least one lesion, before the start of any antimicrobials.
      Efforts should be made for optimal management of brain abscess samples, for
      reliable microbiological documentation. Empirical treatment should cover oral
      streptococci (including milleri group), methicillin-susceptible staphylococci,
      anaerobes and Enterobacteriaceae. As brain abscesses are frequently
      polymicrobial, de-escalation based on microbiological results is safe only when
      aspiration samples have been processed optimally, or when primary diagnosis is
      endocarditis. Otherwise, many experts advocate for anaerobes coverage even with
      no documentation, given the sub-optimal sensitivity of current techniques. A 6
      week combination of third-generation cephalosporin and metronidazole will cure
      most cases of community-acquired brain abscess in immunocompetent patients.
      IMPLICATIONS: Significant advances in brain imaging, minimally invasive
      neurosurgery, molecular biology and antibacterial agents have dramatically
      improved the prognosis of brain abscess in immunocompetent patients over the last
      decades.

PMID- 28501670
TI  - Treg-recruiting microspheres prevent inflammation in a murine model of dry eye
      disease.
AB  - Dry eye disease (DED) is a common ocular disorder affecting millions of
      individuals worldwide. The pathology of DED involves the infiltration of CD4+
      lymphocytes, leading to tear film instability and destructive inflammation. In
      the healthy steady state, a population of immunosuppressive T-cells called
      regulatory T-cells (Treg) regulates proliferation of immune cells that would
      otherwise lead to a disruption of immunological homeostasis. For this reason, it
      has been suggested that Tregs could restore the immunological imbalance in DED.
      To this end, one possible approach would be to recruit the body's own, endogenous
      Tregs in order to enrich them at the site of inflammation and tissue destruction.
      Previously, we have demonstrated a reduction of inflammation and disease symptoms
      in models of periodontitis corresponding to recruitment of endogenous Tregs,
      which was accomplished by local placement of controlled release systems that
      sustain a gradient of the chemokine CCL22, referred to here as Treg-recruiting
      microspheres. Given that DED is characterized by a pro-inflammatory environment
      resulting in local tissue destruction, we hypothesized that the controlled
      release of CCL22 could also recruit Tregs to the ocular surface potentially
      mediating inflammation and symptoms of DED. Indeed, data suggest that Treg
      recruiting microspheres are capable of overcoming the immunological imbalance of
      Tregs and CD4+ IFN-gamma+ cells in the lacrimal gland. Administration of Treg
      recruiting microspheres effectively mitigated the symptoms of DED as measured
      through a number of outcomes such as tear clearance, goblet cells density and
      corneal epithelial integrity, suggesting that recruitment of endogenous Treg can
      mitigate inflammation associated with DED.

PMID- 28501671
TI  - Multifunctional liposomes delay phenotype progression and prevent memory
      impairment in a presymptomatic stage mouse model of Alzheimer disease.
AB  - The failure of clinical trials largely focused on mild to moderate stages of
      Alzheimer disease has suggested to the scientific community that the
      effectiveness of Amyloid-beta (Abeta)-centered treatments should be evaluated
      starting as early as possible, well before irreversible brain damage has
      occurred. Accordingly, also the preclinical development of new therapies should
      be carried out taking into account this suggestion. In the present investigation
      we evaluated the efficacy of a treatment with liposomes multifunctionalized for
      crossing the blood-brain barrier and targeting Abeta, carried out on young
      APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage. Liposomes
      were administered once a week to Tg mice for 7months, starting at the age of
      5months and up to the age of 12 when they display AD-like cognitive and brain
      biochemical/anatomical features. The treatment prevented the onset of the long
      term memory impairment and slowed down the deposition of brain Abeta; at
      anatomical level, prevented both ventricle enlargement and entorhinal cortex
      thickness reduction, otherwise occurring in untreated mice. Strikingly, these
      effects were maintained 3months after treatment discontinuation. An increase of
      Abeta levels in the liver was detected at the end of the treatment, then followed
      also by reduction of brain Amyloid Precursor Protein and increase of Abeta
      degrading enzymes. These results suggest that the treatment promotes brain Abeta
      clearance by a peripheral 'sink' effect and ultimately affects Abeta turnover in
      the brain. Worth of note, the treatment was apparently not toxic for all the
      organs analyzed, in particular for brain, as suggested by the lower brain TNF
      alpha and MDA levels, and by higher level of SOD activity in treated mice.
      Together, these findings promote a very early treatment with multi-functional
      liposomes as a well-tolerated nanomedicine-based approach, potentially suitable
      for a disease-modifying therapy of AD, able to delay or prevent relevant features
      of the disease.

PMID- 28501672
TI  - Combining reactive triblock copolymers with functional cross-linkers: A versatile
      pathway to disulfide stabilized-polyplex libraries and their application as pDNA
      vaccines.
AB  - Therapeutic nucleic acids such as pDNA hold great promise for the treatment of
      multiple diseases. These therapeutic interventions are, however, compromised by
      the lack of efficient and safe non-viral delivery systems, which guarantee
      stability during blood circulation together with high transfection efficiency. To
      provide these desired properties within one system, we propose the use of
      reactive triblock copolypept(o)ides, which include a stealth-like block for
      efficient shielding, a hydrophobic block based on reactive disulfides for cross
      linking and a cationic block for complexation of pDNA. After the complexation
      step, bifunctional cross-linkers can be employed to bio-reversibly stabilize
      derived polyplexes by disulfide bond formation and to introduce endosomolytic
      moieties at the same time. Cross-linked polyplexes show no aggregation in human
      blood serum. Upon cellular uptake and cleavage of disulfide bonds, the cross
      linkers can interact with the endosomal membrane, leading to lysis and efficient
      endosomal translocation. In principal, the approach allows for the combination of
      one polymer with various different cross-linkers and thus enables the fast
      forward creation of a polyplex library. Here, we provide a first insight into the
      potential of this concept and use a screening strategy to identify a lead
      candidate, which is able to transfect dendritic cells with a model DNA vaccine.

PMID- 28501673
TI  - Chemotherapeutic drug-photothermal agent co-self-assembling nanoparticles for
      near-infrared fluorescence and photoacoustic dual-modal imaging-guided chemo
      photothermal synergistic therapy.
AB  - Multimodal imaging-guided synergistic combination therapy has shown great
      potential for cancer treatment. However, the nanocarrier-based theranostic
      systems suffer from batch-to-batch variation, complexity of multicomponent, poor
      drug loading, and carrier-related toxicity issues. To address these issues,
      herein we developed a novel carrier-free theranostic system with nanoscale
      characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual
      modal imaging-guided synergistic chemo-photothermal therapy (PTT). Indocyanine
      green (ICG) and epirubicin (EPI) could co-self-assemble into small molecular
      nanoparticles (NPs) in aqueous solution without any molecular precursor or
      excipient via collaborative interactions (electrostatic, pi-pi stacking, and
      hydrophobic interactions). The exceptionally high dual-drug loading (~92wt%) ICG
      EPI NPs showed good physiological stability, preferable photothermal response,
      excellent NIRF/PA imaging properties, pH-/photo-responsive drug release behavior,
      and promoted cellular endocytosis compared with free ICG or EPI. Importantly, the
      ICG-EPI NPs showed excellent tumor targeting ability with high spatial resolution
      and deep penetration via in vivo NIRF/PA dual-modal imaging. Moreover, in
      comparison with individual chemotherapy or PTT, the combinational chemo-PTT
      therapy of ICG-EPI NPs with NIR laser irradiation synergistically induced
      apoptosis and death of cancer cells in vitro, and showed synergistic chemo-PTT
      efficiency in vivo as evidenced by highly efficient tumor ablation. Furthermore,
      the ICG-EPI NPs exhibited inappreciable toxicity. This co-self-assembly of both
      FDA-approved agents provides a safe and "Molecular economical" strategy in the
      rational design of multifunctional nano-theranostic systems for real-time self
      monitoring intracellular drug delivery and targeting multimodal imaging-guided
      synergistic combination therapy.

PMID- 28501674
TI  - Target attainment with continuous dosing of piperacillin/tazobactam in critical
      illness: a prospective observational study.
AB  - Optimal dosing of beta-lactam antibiotics in critically ill patients is a
      challenge given the unpredictable pharmacokinetic profile of this patient
      population. Several studies have shown intermittent dosing to often yield
      inadequate drug concentrations. Continuous dosing is an attractive alternative
      from a pharmacodynamic point of view. This study evaluated whether, during
      continuous dosing, piperacillin concentrations reached and maintained a pre
      defined target in critically ill patients. Adult patients treated with
      piperacillin by continuous dosing in the intensive care unit of a university
      medical centre in The Netherlands were prospectively studied. Total and unbound
      piperacillin concentrations drawn at fixed time points throughout the entire
      treatment course were determined by liquid chromatography-tandem mass
      spectrometry. A pharmacokinetic combined target of a piperacillin concentration
      >=80 mg/L, reached within 1 h of starting study treatment and maintained
      throughout the treatment course, was set. Eighteen patients were analysed. The
      median duration of monitored piperacillin treatment was 60 h (interquartile
      range, 33-96 h). Of the 18 patients, 5 (27.8%) reached the combined target; 15
      (83.3%) reached and maintained a less strict target of >16 mg/L. In this patient
      cohort, this dosing schedule was insufficient to reach the pre-defined target.
      Depending on which target is to be met, a larger initial cumulative dose is
      desirable, combined with therapeutic drug monitoring.

PMID- 28501675
TI  - Predicting heavy episodic drinking using an extended temporal self-regulation
      theory.
AB  - INTRODUCTION: Alcohol consumption contributes significantly to the global burden
      from disease and injury, and specific patterns of heavy episodic drinking
      contribute uniquely to this burden. Temporal self-regulation theory and the dual
      process model describe similar theoretical constructs that might predict heavy
      episodic drinking. The aims of this study were to test the utility of temporal
      self-regulation theory in predicting heavy episodic drinking, and examine whether
      the theoretical relationships suggested by the dual-process model significantly
      extend temporal self-regulation theory. METHODS: This was a predictive study with
      149 Australian adults. Measures were questionnaires (self-report habit index,
      cues to action scale, purpose-made intention questionnaire, timeline follow-back
      questionnaire) and executive function tasks (Stroop, Tower of London, operation
      span). Participants completed measures of theoretical constructs at baseline and
      reported their alcohol consumption two weeks later. Data were analysed using
      hierarchical multiple linear regression. RESULTS: Temporal self-regulation theory
      significantly predicted heavy episodic drinking (R2=48.0-54.8%, p<0.001) and the
      hypothesised extension significantly improved the prediction of heavy episodic
      drinking frequency (DeltaR2=4.5%, p=0.001) but not peak consumption
      (DeltaR2=1.4%, p=0.181). Intention and behavioural prepotency directly predicted
      heavy episodic drinking (p<0.01). Planning ability moderated the intention
      behaviour relationship and inhibitory control moderated the behavioural
      prepotency-behaviour relationship (p<0.05). CONCLUSIONS: Both temporal self
      regulation theory and the extended temporal self-regulation theory provide good
      prediction of heavy episodic drinking. Intention, behavioural prepotency,
      planning ability and inhibitory control may be good targets for interventions
      designed to decrease heavy episodic drinking.

PMID- 28501676
TI  - Does the implementation of evidence-based and culturally competent practices
      reduce disparities in addiction treatment outcomes?
AB  - RATIONALE: Research is limited on the extent to which implementation of evidence
      based and culturally responsive practices reduces outcome disparities in
      substance use disorder treatment. We examined the role of contingency management
      treatment (CMT), medication-assisted treatment (MAT), and culturally competent
      practices on Mexican Americans' rate of successful completion of treatment.
      METHODS: We analyzed a concatenated dataset from 153 publicly funded substance
      use disorder treatment programs in Los Angeles County, California, in 2011 and
      2013. These data were merged with data from 15,412 adult clients in both periods,
      of whom we selected only Mexican Americans (46.3%) and non-Latino Whites (53.7%).
      The outcome was successful treatment completion. The main independent variables
      were client demographics, drug use severity, mental health issues, and program
      license and professional accreditation. RESULTS: Less than half of the programs
      highly implemented CMT, MAT, and culturally competent practices. CMT and cultural
      competence were not associated with successful treatment completion. However,
      Mexican Americans in programs with high degree of implementation of MAT had
      higher odds of successfully completing treatment compared to non-Latino Whites
      and programs with low MAT (OR=1.389; 95% CI=1.018, 1.897). CONCLUSIONS: Findings
      highlight the role of MAT in reducing the disparity in treatment completion
      between Mexican Americans and non-Latino Whites. Implications for health policy
      and the dissemination of MAT are discussed.

PMID- 28501677
TI  - Modeling variability in air pollution-related health damages from individual
      airport emissions.
AB  - In this study, we modeled concentrations of fine particulate matter (PM2.5) and
      ozone (O3) attributable to precursor emissions from individual airports in the
      United States, developing airport-specific health damage functions (deaths per
      1000t of precursor emissions) and physically-interpretable regression models to
      explain variability in these functions. We applied the Community Multiscale Air
      Quality model using the Decoupled Direct Method to isolate PM2.5- or O3-related
      contributions from precursor pollutants emitted by 66 individual airports. We
      linked airport- and pollutant-specific concentrations with population data and
      literature-based concentration-response functions to create health damage
      functions. Deaths per 1000t of primary PM2.5 emissions ranged from 3 to 160
      across airports, with variability explained by population patterns within 500km
      of the airport. Deaths per 1000t of precursors for secondary PM2.5 varied across
      airports from 0.1 to 2.7 for NOx, 0.06 to 2.9 for SO2, and 0.06 to 11 for VOCs,
      with variability explained by population patterns and ambient concentrations
      influencing particle formation. Deaths per 1000t of O3 precursors ranged from 
      0.004 to 1.0 for NOx and 0.03 to 1.5 for VOCs, with strong seasonality and
      influence of ambient concentrations. Our findings reinforce the importance of
      location- and source-specific health damage functions in design of health
      maximizing emissions control policies.

PMID- 28501678
TI  - The risk of venous thromboembolism with aspirin compared to anticoagulants after
      hip and knee arthroplasty.
AB  - BACKGROUND: Recent guidelines include aspirin as an option to prevent venous
      thromboembolism (VTE) in selected patients undergoing hip or knee replacement
      surgery. However, the efficacy of aspirin after arthroplasty has not been well
      defined, particularly in more contemporary patient populations. We compared rates
      of post-operative VTE between patients who received aspirin-only versus
      anticoagulants after hip or knee arthroplasty, using data from a large US-based
      administrative database. MATERIALS AND METHODS: We conducted a retrospective
      cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621
      who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic
      VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery.
      We compared the risk of post-operative VTE between patients receiving aspirin
      only vs. anticoagulants, controlling for clinical and hospital characteristics
      using multivariable logistic regression with propensity score adjustment.
      RESULTS: Aspirin-only prophylaxis was administered to 7.5% of patients after knee
      arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in
      2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip
      arthroplasty. Compared to anticoagulants, aspirin was not associated with a
      higher risk for post-operative VTE either after knee arthroplasty (adjusted odds
      ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR
      0.82 [0.45-1.51]). CONCLUSIONS: Aspirin was uncommonly administered as the sole
      prophylactic agent after hip or knee arthroplasty in this study. However,
      patients who received aspirin-only had similar rates of post-operative VTE
      compared to patients who received anticoagulants. Further research should focus
      on distinguishing which patients benefit more from anticoagulants versus aspirin
      after arthroplasty.

PMID- 28501679
TI  - Factor structure and longitudinal measurement invariance of PHQ-9 for specialist
      mental health care patients with persistent major depressive disorder:
      Exploratory Structural Equation Modelling.
AB  - BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) is a widely used
      instrument for measuring levels of depression in patients in clinical practice
      and academic research; its factor structure has been investigated in various
      samples, with limited evidence of measurement equivalence/invariance (ME/I) but
      not in patients with more severe depression of long duration. This study aims to
      explore the factor structure of the PHQ-9 and the ME/I between treatment groups
      over time for these patients. METHODS: 187 secondary care patients with
      persistent major depressive disorder (PMDD) were recruited to a randomised
      controlled trial (RCT) with allocation to either a specialist depression team arm
      or a general mental health arm; their PHQ-9 score was measured at baseline, 3, 6,
      9 and 12 months. Exploratory Structural Equational Modelling (ESEM) was performed
      to examine the factor structure for this specific patient group. ME/I between
      treatment arm at and across follow-up time were further explored by means of
      multiple-group ESEM approach using the best-fitted factor structure. RESULTS: A
      two-factor structure was evidenced (somatic and affective factor). This two
      factor structure had strong factorial invariance between the treatment groups at
      and across follow up times. LIMITATIONS: Participants were largely white British
      in a RCT with 40% attrition potentially limiting the study's generalisability.
      Not all two-factor modelling criteria were met at every time-point. CONCLUSION:
      PHQ-9 has a two-factor structure for PMDD patients, with strong measurement
      invariance between treatment groups at and across follow-up time, demonstrating
      its validity for RCTs and prospective longitudinal studies in chronic moderate to
      severe depression.

PMID- 28501680
TI  - Dilated Virchow-Robin spaces in the hippocampus impact behaviors and effects of
      anti-depressant treatment in model of depressed rats.
AB  - The occurrences of dilated Virchow-Robin spaces (dVRSs) and inflammatory factors
      were closely related with development of depression and antidepressants. The
      present study indicated accumulation of inflammatory factors in dVRSs played a
      practical role in behaviors and the treatment-resistant in rats with depression.
      Eighty-one male Wistar rats were exposed to chronic unpredictable mild stress
      (CUMS) until the model was successfully established. According to the detection
      of dVRSs on 7 T structural magnetic resonance imaging (MRI), rats were divided
      into two groups (45 CUMSnon-dVRSs rats and 36 CUMSdVRSs rats). Subsequently,
      different antidepressant treatment (nontreat, aspirin, fluoxetine,
      fluoxetine+aspirin) was given to the two groups, respectively. Sucrose preference
      test (SPT), forced swim test (FST) and morris water maze (MWM) was used to test
      the behaviors of rats. ELISA and Western blot was used to determine the levels of
      inflammatory factors. Compared with the negative control (NC) group, there were
      obvious behavioral abnormalities and increased inflammatory factors in the
      CUMSnon-dVRSs rats. Interestingly, these changes were more significant in the
      CUMSdVRSs rats. In addition, the efficacy of fluoxetine was only found in CUMSnon
      dVRSs rats rather than CUMSdVRSs rats. Meanwhile, behaviors and levels of
      inflammatory factor in hippocampus were ameliorated in the aspirin group of
      CUMSdVRSs rats, and these effects were significantly enhanced in the
      fluoxetine+aspirin group. The dVRSs in the hippocampus might exacerbate
      depression-like behaviors and the effects of antidepressant treatment in
      depressed rats by increasing the levels of inflammatory factors.

PMID- 28501681
TI  - Postnatal paternal involvement and maternal emotional disturbances: The effect of
      maternal employment status.
AB  - BACKGROUND: Recently, studies have begun emphasizing paternal involvement during
      the perinatal period and its impact on maternal health. However, most studies
      have assessed maternal perception and focused on adolescents or minority groups
      in Western countries. Therefore, the current study investigated the association
      between paternal involvement and maternal postnatal depression and anxiety, along
      with the effects of maternal job status in the Asian society of Taiwan. METHODS:
      This study recruited pregnant women in the first trimester of pregnancy as well
      as their partners on prenatal visits from July 2011 to September 2013 at four
      selected hospitals in metropolitan areas of Taipei, Taiwan. In total, 593
      parental pairs completed the first interview and responded to the follow-up
      questionnaires until 6 months postpartum. Self-reported data were collected, and
      multiple logistic regression models were used for analyses. RESULTS: Lower
      paternal childcare and nursing frequency was independently associated with an
      increased risk of maternal postpartum depression (adjusted odds ratio (OR) =4.33,
      95% confidence interval (CI)=1.34-13.98), particularly among unemployed mothers.
      Furthermore, among unemployed mothers, the risk of postnatal anxiety was 3.14
      times higher in couples with fathers spending less time with the child, compared
      with couples with fathers spending more time (95% CI=1.10-8.98). However, no
      significant findings were obtained for employed mothers. CONCLUSIONS: The high
      prevalence of maternal postnatal emotional disturbances warrants continual
      consideration. Higher paternal involvement in childcare arrangements should be
      emphasized to aid in ameliorating these maternal emotional disturbances,
      particularly among unemployed mothers.

PMID- 28501682
TI  - The role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV and Rho
      kinase in H2S-induced relaxation in the mouse corpus cavernosum.
AB  - BACKGROUND: Penile corpus cavernosum is an extremely vascularized tissue and
      cavernosal smooth muscle tone is regulated by the balance between contractile and
      relaxant factor. We investigated the possible role of arachidonic
      acid/cyclooxygenase cascade, phosphodiesterase IV (PDEIV) and Rho-kinase in
      exogenous hydrogen sulfide (H2S)-induced relaxation in mouse corpus cavernosum.
      METHODS: The relaxant response to H2S (NaHS as exogenous H2S; 1-1000MUM) were
      obtained in isolated mouse corpus cavernosum tissues which pre-contracted by
      phenylephrine (5MUM). The effects of 4-(4-octadecylphenyl)-4-oxobutenoic acid
      (OBAA; 10MUM), a selective phospholipase A2 (PLA2) inhibitor, indomethacin
      (1MUM), a non-selective cyclooxygenase (COX) inhibitor, baicalein (10MUM), a
      lipoxygenase (LOX) inhibitor, and proadifen (10MUM), cytochrome P450 inhibitor,
      on the relaxant responses to H2S were investigated. Furthermore, the effects of
      theophylline (500MUM) and rolipram (1MUM), a non-selective and selective PDEIV
      inhibitor, and fasudil (3MUM), a specific Rho-kinase inhibitor, were studied on
      H2S-induced relaxation. RESULTS: H2S-induced relaxations were significantly
      reduced by OBAA, indomethacin and proadifen but not baicalein. Furthermore,
      theophylline, rolipram and fasudil reduced H2S-induced relaxations. CONCLUSION:
      These results suggest that PLA2, COX, cytochrome P450, PDEIV and Rho-kinase
      pathway may involve in H2S-induced relaxation in mouse corpus cavernosum tissues.

PMID- 28501683
TI  - Efficiency of an upflow anaerobic sludge blanket reactor treating potato starch
      processing wastewater and related process kinetics, functional microbial
      community and sludge morphology.
AB  - Herein, an upflow anaerobic sludge blanket reactor was employed to treat potato
      starch processing wastewater and the efficacy, kinetics, microbial diversity and
      morphology of sludge granules were investigated. When organic loading rate (OLR)
      ranging from 2.70 to 13.27kgCOD/m3.d was implemented with various hydraulic
      retention times (72h, 48h and 36h), COD removal could reach 92.0-97.7%. Highest
      COD removal (97.7%) was noticed when OLR was 3.65kgCOD/m3.d, but had declined to
      92.0% when OLR was elevated to 13.27kgCOD/m3.d. Methane and biogas production
      increased from 0.48 to 2.97L/L.d and 0.90 to 4.28L/L.d, respectively. Kinetics
      and predictions by modified-Gompertz model agreed better with experimental data
      as opposed to first-order kinetic model. Functional population with highest
      abundance was Chloroflexi (28.91%) followed by Euryarchaeota (22.13%), Firmicutes
      (16.7%), Proteobacteria (16.25%) and Bacteroidetes (7.73%). Compared with top
      sludge, tightly-bound extracellular polymeric substances was high within bottom
      and middle sludge. Morphology was predominantly Methanosaeta-like cells,
      Methanosarcina-like cells, rods and cocci colonies.

PMID- 28501684
TI  - Ultrasonic hyperactivation of cellulase immobilized on magnetic nanoparticles.
AB  - In the present work, effect of low power, low frequency ultrasound on cellulase
      immobilized magnetic nanoparticles (cellulase@MNPs) was studied. To gain maximum
      activity recovery in cellulase@MNPs various parameters viz. ratio of
      MNPs:cellulase, concentration of glutaraldehyde and cross-linking time were
      optimized. The influence of ultrasonic power on cellulase@MNPs was studied. Under
      ultrasonic conditions at 24kHz, 6W power, and 6min of incubation time there was
      almost 3.6 fold increased in the catalytic activity of immobilized cellulase over
      the control. Results also indicated that there was improvement in pH and
      temperature stability of cellulase@MNPs. Furthermore, thermal deactivation energy
      required was more in cellulase@MNPs than that of the free cellulase. Secondary
      structural analysis revealed that there were conformational changes in free
      cellulase and cellulase@MNPs before and after sonication which might be
      responsible for enhanced activity after ultrasonication. Finally, the influence
      of ultrasound and cellulase@MNPs for biomass hydrolysis was studied.

PMID- 28501685
TI  - Lipid for biodiesel production from attached growth Chlorella vulgaris biomass
      cultivating in fluidized bed bioreactor packed with polyurethane foam material.
AB  - The potential to grow attached microalgae Chlorella vulgaris in fluidized bed
      bioreactor was materialized in this study, targeting to ease the harvesting
      process prior to biodiesel production. The proposed thermodynamic mechanism and
      physical property assessment of various support materials verified polyurethane
      to be suitable material favouring the spontaneous adhesion by microalgae cells.
      The 1-L bioreactor packed with only 2.4% (v/v) of 1.00-mL polyurethane foam cubes
      could achieve the highest attached growth microalgae biomass and lipid weights of
      812+/-122 and 376+/-37mg, respectively, in comparison with other cube sizes. The
      maturity of attached growth microalgae biomass for harvesting could also be
      determined from the growth trend of suspended microalgae biomass. Analysis of
      FAME composition revealed that the harvested microalgae biomass was dominated by
      C16-C18 (>60%) and mixture of saturated and mono-unsaturated fatty acids (>65%),
      satiating the biodiesel standard with adequate cold flow property and oxidative
      stability.

PMID- 28501686
TI  - Immobilisation on mesoporous silica and solvent rinsing improve the
      transesterification abilities of feruloyl esterases from Myceliophthora
      thermophila.
AB  - The immobilisation of four feruloyl esterases (FAEs) (FaeA1, FaeA2, FaeB1, FaeB2)
      from the thermophilic fungus Myceliophthora thermophila C1 was studied and
      optimised via physical adsorption onto various mesoporous silica particles with
      pore diameters varying from 6.6nm to 10.9nm. Using crude enzyme preparations,
      enrichment of immobilised FAEs was observed, depending on pore diameter and
      protein size. The immobilised enzymes were successfully used for the synthesis of
      butyl ferulate through transesterification of methyl ferulate with 1-butanol.
      Although the highest butyl ferulate yields were obtained with free enzyme, the
      synthesis-to-hydrolysis ratio was higher when using immobilised enzymes. Over 90%
      of the initial activity was observed in a reusability experiment after nine
      reaction cycles, each lasting 24h. Rinsing with solvent to remove water from the
      immobilised enzymes further improved their activity. This study demonstrates the
      suitability of immobilised crude enzyme preparations in the development of
      biocatalysts for esterification reactions.

PMID- 28501687
TI  - The effects of combined agricultural phytohormones on the growth, carbon
      partitioning and cell morphology of two screened algae.
AB  - Applying phytohormones has been considered a promising way to increase lipid
      productivity of microalgae recently. Eight dosages of auxin phytohormones were
      tested to exploit the effects and mechanism of such stimulants on microalgae. The
      optimal one was 20mgL-1, leading to an increase in biomass concentration of 59.3%
      for Scenedesmus sp. SDEC-8 and 76.6% for Chlorella sorokiniana SDEC-18, meanwhile
      the lipid content rose from 18.74% to 56.17% (SDEC-8) and from 19.69% to 55.76%
      (SDEC-18). Proton pumps were activated by the stimulants, causing excretion of
      H+, which resulted in pH decline and a favorable condition for growth. Pigments
      changes implied that hormones strengthened the dark reactions of photosynthesis.
      Auxin addition led to a 3MUm increase in diameter for C. sorokiniana SDEC-18 and
      altered the cellular pattern of Scenedesmus sp. SDEC-8, which improved the cells
      elongation. Therefore, supplement of auxin phytohormones simultaneously increased
      the viability and lipid production of microalgae.

PMID- 28501688
TI  - Influence of pre-treatment on torrefaction of Phyllostachys edulis.
AB  - This study investigated the effects of different pre-treatments on structural
      changes in Phyllostachys edulis. Samples were pretreated with water, 15% ammonia
      water, 2% sulfuric acid, hydrothermal carbonization, and ball milling. Moreover,
      ultrasound was introduced. The influence of pre-treatment on the physiochemical
      property and composition of P. edulis were studied. Moreover, torrefaction
      characterization was performed and the distribution of torrefaction products of
      pretreated samples was determined. Results showed that pre-treatment effectively
      modified physiochemical structure and the torrefaction property of P. edulis. The
      pretreatment reduced the ash content and increased the bio-oil content of the
      torrefaction products. Compared with that of the raw material, the residual bio
      char content of the pretreated samples decreased by 2-8%, and degradation
      temperature of bio-char fluctuated between 365 degrees C and 321 degrees C. The
      distribution of bio-oil contents, bio-char, and bio-gas in the torrefaction
      products significantly varied with pretreatments methods.

PMID- 28501689
TI  - Obtaining titanium dioxide nanoparticles with spherical shape and antimicrobial
      properties using M. citrifolia leaves extract by hydrothermal method.
AB  - In this work, we synthesized titanium dioxide (TiO2) nanoparticles using leaf
      extract of Morinda citrifolia (M. citrifolia) by the advanced hydrothermal
      method. The synthesized TiO2 nanoparticles were characterized by X-ray
      diffraction (XRD), Fourier transmission infrared (FT-IR), Ultraviolet-visible
      diffuse reflectance (UV-Vis DRS), Ultraviolet-visible spectroscopy (UV-Vis),
      Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray
      spectroscopy (SEM with EDX) techniques. The XRD major peak at 27.3 degrees 
      corresponds to the (110) lattice plane of tetragonal rutile TiO2 phase and
      average crystalline size of nanoparticles is 10nm. The FT-IR result confirmed
      that TiO2 nanoparticles and the presences of very few amount of anthraquinone and
      phenolic compounds of the leaf extract. The obtained nanoparticles were also
      characterized by UV-Vis DRS absorption spectroscopy and an intense band at 423nm
      clearly reveals the formation of nanoparticles. SEM images with EDX spectra
      clearly reveal the size of the nanoparticles, between 15 and 19nm in excellent
      quasi-spherical shape, by virtue of stabilization (capping) agent. The presence
      of elements-titanium and oxygen was verified with EDX spectrum. Furthermore, the
      inhibitory activity of green synthesized TiO2 nanoparticles was tested against
      human pathogens like Staphylococcus aureus, Escherichia coli, Bacillus subtilis,
      Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger by the agar well
      diffusion method. The TiO2 nanoparticles exhibited superior antimicrobial
      activity against Gram-positive bacteria, demonstrating their antimicrobial value
      against pathogenic diseases.

PMID- 28501690
TI  - Toxicity estimates for diuron and atrazine for the tropical marine cnidarian
      Exaiptasia pallida and in-hospite Symbiodinium spp. using PAM chlorophyll-a
      fluorometry.
AB  - Effective ecotoxicological risk assessments for herbicides in tropical marine
      environments are restricted by a lack of toxicity data, sensitive test methods
      and endpoints for relevant species, and this requires rectification. The
      symbiotic sea anemone Exaiptasia pallida is a suitable test species, representing
      the phylum Cnidaria and allowing for assessments of toxicological responses of
      both the animal host and in-hospite Symbiodinium spp. Pulse amplitude modulated
      (PAM) chlorophyll-a fluorometry is recognised as a valuable ecotoxicological
      tool, and here newly-developed test methods are presented using PAM fluorometry
      to measure herbicide effects on photosynthetic efficiency of in-hospite
      Symbiodinium spp. Additionally, measurements on healthy laboratory-reared E.
      pallida provide baseline data demonstrating the normal effective quantum yield
      (EQY) and the maximum electron transport rate (ETRm) for Symbiodinium spp. in the
      absence of herbicide stress. Concentration-dependant reductions in the EQY and
      ETRm occurred during diuron and atrazine exposures; a mean 48-h EC50 (effective
      concentration; 50%) of 8MUg/L of diuron was estimated, however atrazine elicited
      a much lower toxicity. Twelve-day exposures to 10-200MUg/L diuron showed that the
      greatest EQY effect occurred during the first 48h, with little subsequent change.
      However, longer exposures to the lowest diuron treatment (1MUg/L) showed the
      lowest EQYs after 96h followed by recovery to control levels within 12d.
      Furthermore, asexual reproduction was inhibited during 12-d exposures to diuron,
      and 12-d EC50 values of 100 and 132MUg/L were estimated to inhibit successful
      reproduction of pedal lacerates and juveniles by 50% respectively. This study
      provides much needed data contributions to species sensitivity curves for
      development of diuron and atrazine water quality guidelines in tropical marine
      environments.

PMID- 28501691
TI  - Biosynthesis and characterization of copper oxide nanoparticles and its
      anticancer activity on human colon cancer cell lines (HCT-116).
AB  - The eco-friendly synthesis of nanoparticles through green route from plant
      extracts have renowned a wide range of application in the field of modern
      science, due to increased drug efficacy and less toxicity in the nanosized
      mediated drug delivery model. In the present study, our research groups have
      biosynthesized the stable and cost effective copper oxide nanoparticles (CuO NPs)
      from the leaves of (Ormocarpum cochinchinense) O. cochinchinense. The synthesis
      of crystalline CuO NPs from the leaf extract of O. cochinchinense were confirmed
      by various analytical techniques like UV-Visible Spectroscopy (UV-Vis), Fourier
      Transform Infrared Spectroscopy (FT-IR), X-Ray Diffractometer (XRD), Scanning
      Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Selected
      Area Electron Diffraction (SAED) pattern. Further the synthesized CuO NPs were
      screened for anticancer activity on human colon cancer cell lines (HCT-116) by
      MTT (3-(4,5-dimethyl-2-tiazolyl)-2,5-diphenyl-2-tetrazolium bromide) assay. The
      obtained result inferred that the synthesized CuO NPs demonstrated high
      anticancer cytotoxicity on human colon cancer cell lines (HCT-116) with IC50
      value of 40MUgmL-1 were discussed briefly in this manuscript.

PMID- 28501692
TI  - Trans-chalcone added in topical formulation inhibits skin inflammation and
      oxidative stress in a model of ultraviolet B radiation skin damage in hairless
      mice.
AB  - Trans-chalcone (TC) is a common precursor of flavonoids. However, the
      pharmacological properties of TC remain to be fully understood. The present study
      investigated whether topical formulation containing TC (TFcTC) presents
      therapeutic effect in UVB radiation-induced skin damage using disease, enzyme
      activity, antioxidant activity, protein and mRNA parameters. Control topical
      formulation (CTF) and TFcTC were applied in hairless mice before and after
      exposure to UVB radiation. Dorsal skin samples were collected after UVB exposure
      to evaluate: i) skin edema (weight) was measured by punch biopsy; ii)
      spectrophotometric assays were used to measure myeloperoxidase (MPO) and catalase
      activities, ferric (FRAP) and ABTS cation reducing antioxidant power, superoxide
      anion production and levels of reduced glutathione (GSH); iii) enzymography was
      used to measure matrix metalloproteinase-9 (MMP-9) activity; iv)
      chemiluminescence was used to measure the lipid peroxidation (LPO); v) enzyme
      linked immunosorbent assay (ELISA) was used to measure tumor necrosis factor
      alpha (TNF-alpha) levels; vi) reverse transcription quantitative PCR (RT-qPCR)
      was used to measure cyclooxygenase-2 (COX-2), gp91phox (NADPH oxidase sub-unity),
      glutathione peroxidase-1 (Gpx1), glutathione reductase (Gr), nuclear factor
      erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) mRNA expression.
      TFcTC inhibited UVB-induced skin edema, MPO activity, MMP-9 activity, TNF-alpha
      production, and COX-2 mRNA expression. TFcTC inhibited UVB-induced LPO, down
      regulated superoxide anion levels and gp91phox mRNA expression, and improved
      antioxidant potential and GSH skin levels. The mRNA expression of detoxification
      systems such as Nrf2, HO-1, Gpx1 and Gr, and catalase activity were also enhanced
      by treatment with TFcTC. In conclusion, TFcTC protects mice skin from UVB
      radiation by inhibiting inflammation, and improving antioxidant and
      detoxification systems. Therefore, topical treatment with TC is a novel
      therapeutic approach for the treatment of UVB radiation skin damages, which
      merits further pre-clinical and clinical investigation.

PMID- 28501694
TI  - 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid attenuates spontaneous
      recurrent seizures and vasogenic edema following lithium-pilocarpine induced
      status epilepticus.
AB  - Vasogenic edema induced by blood brain barrier disruption and neuronal loss play
      an important role in the epileptogenic process. 4,4'- diisothiocyanatostilbene
      2,2'-disulfonic acid (DIDS) is a commonly used anion channel inhibitor that has
      been reported to exert an anticonvulsant effect in rat hippocampus in vitro. The
      present study aimed to investigate whether DIDS could prevent epileptogenic
      process in rat lithium-pilocarpine model of temporal lobe epilepsy. The tight
      junction proteins and serum extravasation were examined in the piriform cortex
      3days after status epilepticus. The findings showed that status epilepticus
      induced vasogenic edema. Based on these findings, rats were
      intracerebroventricularly infused with saline and DIDS 1 week after surgery, DIDS
      reduced vasogenic edema and prevented neuronal loss following status epilepticus
      in the piriform cortex. Moreover, spontaneous recurrent seizures were recorded by
      continuous video monitoring. DIDS significantly reduced the frequency and
      duration of spontaneous recurrent seizures from day 28 to day 42 post status
      epilepticus. These findings demonstrated that DIDS attenuated vasogenic edema and
      neuronal apoptosis and might exert disease-modifying effect in animal model of
      temporal lobe epilepsy. These results explored a novel therapeutic strategy for
      treatment of epilepsy.

PMID- 28501693
TI  - Necrostatin-1 protects hippocampal neurons against ischemia/reperfusion injury
      via the RIP3/DAXX signaling pathway in rats.
AB  - Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in
      CA1 region of hippocampus, leading to severe impairment in behavior, learning and
      memory functions. However, the molecular mechanism underlying the processes was
      not elucidated clearly. RIP3 is a key molecular switch connecting apoptosis,
      necrosis and necroptosis. DAXX, as a novel substrate of RIP3, plays a vital role
      in ischemia-induced neuronal death. The aim of this study is to investigate the
      role and mechanism of RIP3/DAXX signaling pathway on neurons in CA1 region of the
      rat hippocampus after cerebral I/R. Global cerebral ischemia was induced by the
      method of four-vessel occlusion. RIP1 specific inhibitor Necrostatin-1 was
      administered by intracerebroventricular injection 1h before ischemia. Open-field,
      closed-field, and Morris water maze tests were performed respectively to examine
      the anxiety and cognitive behavior in each group. Hematoxylin and eosinstaining
      was used to examine the survival of hippocampal CA1 pyramidal neurons. Western
      blot or immunoprecipitation were carried to detect protein expression,
      phosphorylation, and interaction. We found that pre-treatment with Nec-1
      protected locomotive ability, relieved anxiety behavior, and improved cognitive
      ability in the rats subjected to cerebral I/R. In addition Moreover, Nec-1
      decreased significantly the dead rate of neurons in hippocampal CA1 region after
      cerebral I/R through suppressing RIP1-RIP3 interaction and RIP3 activation along
      with RIP3-DAXX interaction, and then blocked DAXX translocation from nucleaus to
      cytoplasm, which resulted in the inactiviation of DAXX. We concluded that pre
      treatment with Nec-1 can protect neurons in the hippocampal CA1 region against
      ischemic damage through the RIP3-DAXX signaling pathway.

PMID- 28501696
TI  - The role of nitric oxide in anticonvulsant effect of nanocurcumine on
      pentylenetetrazole-induced seizure in mice.
AB  - : A plant alkaloid obtained from Curcuma longa, curcumin possesses anti-oxidant
      and anti-inflammatory effects. Nanoformulations have been developed for
      preclinical studies which demonstrate enhanced therapeutic efficacy. Effect of
      acute intraperitoneal (i.p.) administration of curcumin C3 complex nanoparticles
      [1,5, 10, 20, 40, 80mg/kg, (i.p.)] 75min prior to PTZ, on clonic seizure
      thresholds induced by intravenous infusion of pentylenetetrazole (PTZ) 0.5% was
      investigated in comparison with curcumin (40 and 80mg/kg, i.p.) in male mice.
      Moreover, to clarify the probable role of NO in the anticonvulsant property of
      nanocurcumin, non-effective doses of l-arginine (l-Arg), a NO donor; 7
      nitroindazole, 7-NI, a preferential neuronal NO synthase inhibitor; L-NAME, a non
      selective NO synthase inhibitor and aminoguanidine (AG), a selective inducible NO
      synthase inhibitor (iNOS), in combination with nanocurcumin (80mg/kg, i.p.), 15
      30min before it were employed. RESULTS: While curcumin did not show any
      anticonvulsant effect, nanocurcumin revealed dose-dependent anticonvulsant
      property at the doses 20, 40 and 80mg/kg, P<0.01, P<0.01 and P<0.001,
      respectively. l-Arg (30 and 60mg/kg) dose-dependently reversed the anticonvulsant
      effect of the most effective nanocurcumin dose (80mg/kg), P<0.01 and P<0.001,
      respectively. On the other hand, L-NAME (3 and 10mg/kg, i.p.) markedly
      potentiated the sub effective dose of nanocurcumin (10mg/kg), P<0.01 and P<0.001,
      respectively. Similarly, AG (50 and 100mg/kg, i.p.) profoundly augmented the
      seizure thresholds of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively.
      In addition, 7-NI (10, 30 and 60mg/kg, i.p.) failed to influence the responses.
      CONCLUSION: These data may support excess of NO production following PTZ infusion
      probably resulting from iNOS source. Consequently, nanocurcumin probably down
      regulated NO. To conclude, nanocurcumin showed anticonvulsant effect.
      Furthermore, this effect was reversed following l-arginine as an external NO
      precursor. However, both the non-selective NOS inhibitor and selective iNOS
      inhibitor increased the thresholds. It is evident that nanocurcumin may influence
      the seizure thresholds at least in part through a decrease in NO.

PMID- 28501695
TI  - Expression of aromatase and estrogen receptors in lumbar motoneurons of mice.
AB  - Estrogen exerts protective roles in amyotrophic lateral sclerosis (ALS). However,
      the expression of aromatase (ARO) and estrogen receptors (ERs) in the motoneurons
      of spinal cord, has not yet been elucidated. By immunohistochemistry, we found
      that ARO and ERs were present in the ventral horn of adult mice lumbar spinal
      cord, and colocalized with SMI-32, a motoneuron specific marker. Within
      motoneurons, we observed that ARO is detected primarily in the cytoplasm, with
      fewer ARO in the nucleus; ERalpha and ERbeta mainly localized in the nucleus with
      less in the cytoplasm; while GPR30 is located in soma and processes. In
      conclusion, we found that ERs and ARO are expressed in the motoneurons of lumbar
      spinal cord in adult mice. These findings suggest that estrogen may be useful as
      a promising therapeutic agent for prevention of damage and improvement of
      locomotor function in ALS.

PMID- 28501697
TI  - Intentional binding as a marker of agency across the lifespan.
AB  - The feeling of control over actions and their external effects is known as Sense
      of Agency (SoAg). People usually have a distinctive SoAg for events caused by
      their own actions. However, if the agent is a child or an older person, this
      feeling of being responsible for the consequences of an action may differ from
      what an adult would feel. The idea would be that children and elderly may have a
      reduced SoAg since their frontal lobes are developing or have started to loose
      their efficiency. The aim of this study was to elucidate whether the SoAg changes
      across lifespan, using the Intentional Binding (i.e., the temporal attraction
      between a voluntary action and its sensory consequence) as implicit measure. Data
      show that children and elderly are characterized by a reduced SoAg as compared to
      adults. These findings provide a fundamental step in the characterization of SoAg
      dynamics throughout individuals' lifetime.

PMID- 28501698
TI  - Sensorimotor experience in virtual reality enhances sense of agency associated
      with an avatar.

PMID- 28501699
TI  - The AGES-Reykjavik study atlases: Non-linear multi-spectral template and atlases
      for studies of the ageing brain.
AB  - Quantitative analyses of brain structures from Magnetic Resonance (MR) image data
      are often performed using automatic segmentation algorithms. Many of these
      algorithms rely on templates and atlases in a common coordinate space. Most
      freely available brain atlases are generated from relatively young individuals
      and not always derived from well-defined cohort studies. In this paper, we
      introduce a publicly available multi-spectral template with corresponding tissue
      probability atlases and regional atlases, optimised to use in studies of ageing
      cohorts (mean age 75 +/- 5 years). Furthermore, we provide validation data from a
      regional segmentation pipeline to assure the integrity of the dataset.

PMID- 28501700
TI  - Automatic online layer separation for vessel enhancement in X-ray angiograms for
      percutaneous coronary interventions.
AB  - Percutaneous coronary intervention is a minimally invasive procedure that is
      usually performed under image guidance using X-ray angiograms in which coronary
      arteries are opacified with contrast agent. In X-ray images, 3D objects are
      projected on a 2D plane, generating semi-transparent layers that overlap each
      other. The overlapping of structures makes robust automatic information
      processing of the X-ray images, such as vessel extraction which is highly
      relevant to support smart image guidance, challenging. In this paper, we propose
      an automatic online layer separation approach that robustly separates
      interventional X-ray angiograms into three layers: a breathing layer, a quasi
      static layer and a vessel layer that contains information of coronary arteries
      and medical instruments. The method uses morphological closing and an online
      robust PCA algorithm to separate the three layers. The proposed layer separation
      method ran fast and was demonstrated to significantly improve the vessel
      visibility in clinical X-ray images and showed better performance than other
      related online or prospective approaches. The potential of the proposed approach
      was demonstrated by enhancing contrast of vessels in X-ray images with low vessel
      contrast, which would facilitate the use of reduced amount of contrast agent to
      prevent contrast-induced side effects.

PMID- 28501701
TI  - RadB acts in homologous recombination in the archaeon Haloferax volcanii,
      consistent with a role as recombination mediator.
AB  - Homologous recombination plays a central role in the repair of double-strand DNA
      breaks, the restart of stalled replication forks and the generation of genetic
      diversity. Regulation of recombination is essential since defects can lead to
      genome instability and chromosomal rearrangements. Strand exchange is a key step
      of recombination - it is catalysed by RecA in bacteria, Rad51/Dmc1 in eukaryotes
      and RadA in archaea. RadB, a paralogue of RadA, is present in many archaeal
      species. RadB has previously been proposed to function as a recombination
      mediator, assisting in RadA-mediated strand exchange. In this study, we use the
      archaeon Haloferax volcanii to provide evidence to support this hypothesis. We
      show that RadB is required for efficient recombination and survival following
      treatment with DNA-damaging agents, and we identify two point mutations in radA
      that suppress the DeltaradB phenotype. Analysis of these point mutations leads us
      to propose that the role of RadB is to act as a recombination mediator, which it
      does by inducing a conformational change in RadA and thereby promoting its
      polymerisation on DNA.

PMID- 28501702
TI  - Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in
      rat.
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is
      characterized by anovulation, hyperandrogenism and polycystic ovary. However,
      there is a lack of effective treatment for PCOS at present because the pathologic
      cause of PCOS has not been elucidated. Although it has been known that brown
      adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT
      transplantation is not applicable in clinic. Therefore, BAT activation with
      natural compound could be an effective treatment strategy for PCOS patients.
      Here, we found that 3 weeks of rutin (a novel compound for BAT activation)
      treatment increased BAT activation, thereby it improved thermogenesis and
      systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat.
      In addition, the expression levels of ovarian steroidogenic enzymes such as
      P450C17, aromatase, 3beta-HSD, 17beta-HSD and STAR were up-regulated in rutin
      treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing
      hormone were normalized, and a large number of mature ovulated follicle with a
      reduction of cystic formation were observed in PCOS rat after rutin treatment.
      Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS
      rat. Collectively, our results indicate that rutin treatment significantly
      improves systemic insulin resistance and ovarian malfunction in PCOS, and our
      findings in this study provide a novel therapeutic option for the treatment of
      PCOS by activating BAT with rutin.

PMID- 28501703
TI  - Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse
      cholesterol transport.
AB  - Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus
      L.), is suggested to be antiatherogenic since it reportedly increases high
      density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol
      promotes reverse cholesterol transport (RCT), the most important antiatherogenic
      property of HDL; therefore, we investigated the effects of xanthohumol on
      macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In
      vivo RCT experiments showed that xanthohumol significantly increased fecal
      appearance of the tracer derived from intraperitoneally injected [3H]-cholesterol
      labeled macrophages. Ex vivo experiments were then employed to investigate the
      detailed mechanism by which xanthohumol enhanced RCT. Cholesterol efflux capacity
      from macrophages was 1.5-fold higher in xanthohumol-fed hamsters compared with
      the control group. In addition, protein expression and lecithin-cholesterol
      acyltransferase activity in the HDL fraction were significantly higher in
      xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol
      promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol
      increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions
      of liver X receptor alpha and bile pump export protein were increased in the
      liver by xanthohumol administration when compared with the control, implying that
      it stimulated bile acid synthesis and cholesterol excretion to feces. In
      conclusion, our data demonstrate that xanthohumol improves RCT in vivo through
      cholesterol efflux from macrophages and excretion to feces, leading to
      antiatherosclerosis effects. It remains to be elucidated whether enhancement of
      RCT by xanthohumol could prove valuable in humans.

PMID- 28501706
TI  - Upward counterfactual thinking and depression: A meta-analysis.
AB  - This meta-analysis examined the strength of association between upward
      counterfactual thinking and depressive symptoms. Forty-two effect sizes from a
      pooled sample of 13,168 respondents produced a weighted average effect size of
      r=.26, p<.001. Moderator analyses using an expanded set of 96 effect sizes
      indicated that upward counterfactuals and regret produced significant positive
      effects that were similar in strength. Effects also did not vary as a function of
      the theme of the counterfactual-inducing situation or study design (cross
      sectional versus longitudinal). Significant effect size heterogeneity was
      observed across sample types, methods of assessing upward counterfactual
      thinking, and types of depression scale. Significant positive effects were found
      in studies that employed samples of bereaved individuals, older adults,
      terminally ill patients, or university students, but not adolescent mothers or
      mixed samples. Both number-based and Likert-based upward counterfactual thinking
      assessments produced significant positive effects, with the latter generating a
      larger effect. All depression scales produced significant positive effects,
      except for the Psychiatric Epidemiology Research Interview. Research and
      theoretical implications are discussed in relation to cognitive theories of
      depression and the functional theory of upward counterfactual thinking, and
      important gaps in the extant research literature are identified.

PMID- 28501704
TI  - Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in
      modulating the risk of colorectal polyps.
AB  - Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic
      amino acid transporter 2, which mediates the transport of arginine, lysine and
      ornithine. l-Arginine is necessary for cancer development and progression,
      including an important role in colorectal cancer pathogenesis. Furthermore,
      previous studies found that both calcium and magnesium inhibit the transport of
      arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact
      with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We
      conducted a two-phase case-control study within the Tennessee Colorectal Polyps
      Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the
      SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In
      the second phase conducted in an independent set of 607 cases and 2113 controls,
      we replicated the significant findings in the first phase. We observed that
      rs2720574 significantly interacted with calcium:magnesium intake ratio in
      association with odds of adenoma, particularly multiple/advanced adenoma. In the
      combined analysis, among those with a calcium:magnesium intake ratio below 2.78,
      individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR
      (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68
      (1.28, 2.20)] than those who carried the GG genotype. The P values for
      interactions between calcium:magnesium intake ratio and rs2720574 were .002 for
      all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG
      genotype, a high calcium:magnesium ratio was associated with increased odds of
      colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas
      [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high
      calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64
      (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)].

PMID- 28501705
TI  - Doxorubicin delivered by a redox-responsive dasatinib-containing polymeric
      prodrug carrier for combination therapy.
AB  - Two novel prodrug polymers POEG-b-PSSDas (redox-sensitive) and POEG-b-PCCDas
      (redox-insensitive), which consist of poly(oligo(ethylene glycol) methacrylate)
      (POEG) hydrophilic blocks and dasatinib (DAS, an oncogenic tyrosine kinases
      inhibitor) conjugated hydrophobic blocks, were designed as dual-functional
      carriers for codelivery with doxorubicin (DOX). Both carriers retained antitumor
      activity of DAS and could form mixed micelles with DOX. Compared to POEG-b-PCCDas
      micelles, incorporation of disulfide linkage into POEG-b-PSSDas micelles
      facilitated efficient cleavage of DAS from prodrug micelles in tumor
      cells/tissues, leading to a higher level of anti-tumor activity in vitro and in
      vivo. In addition, DOX-loaded POEG-b-PSSDas micelles exhibited triggered DOX
      release under a redox environment (10mM glutathione, GSH), and demonstrated
      enhanced cytotoxicity against 4T1.2 and PC3 cell lines compared to DOX and DOX
      loaded POEG-b-PCCDas micelles. More importantly, DOX-loaded POEG-b-PSSDas
      micelles were more effective in inhibiting the tumor growth and prolonging the
      survival rate in an aggressive murine breast cancer model (4T1.2) compared to DOX
      loaded POEG-b-PCCDas micelles and a micellar formulation co-loaded with DOX and
      DAS. This redox-responsive prodrug micellar system provides an attractive
      strategy for effective combination of tumor targeted therapy and traditional
      chemotherapy, which warrants further investigation.

PMID- 28501707
TI  - Mechanisms of action in mindfulness-based cognitive therapy (MBCT) and
      mindfulness-based stress reduction (MBSR) in people with physical and/or
      psychological conditions: A systematic review.
AB  - BACKGROUND: Recently, there has been an increased interest in studying the
      effects of mindfulness-based interventions for people with psychological and
      physical problems. However, the mechanisms of action in these interventions that
      lead to beneficial physical and psychological outcomes have yet to be clearly
      identified. PURPOSE: The aim of this paper is to review, systematically, the
      evidence to date on the mechanisms of action in mindfulness interventions in
      populations with physical and/or psychological conditions. METHOD: Searches of
      seven databases (PsycINFO, Medline (Ovid), Cochrane Central Register of
      Controlled Trials, EMBASE, CINAHL, AMED, ClinicalTrials.gov) were undertaken in
      June 2014 and July 2015. We evaluated to what extent the studies we identified
      met the criteria suggested by Kazdin for establishing mechanisms of action within
      a psychological treatment (2007, 2009). RESULTS: We identified four trials
      examining mechanisms of mindfulness interventions in those with comorbid
      psychological and physical health problems and 14 in those with psychological
      conditions. These studies examined a diverse range of potential mechanisms,
      including mindfulness and rumination. Of these candidate mechanisms, the most
      consistent finding was that greater self-reported change in mindfulness mediated
      superior clinical outcomes. However, very few studies fully met the Kazdin
      criteria for examining treatment mechanisms. CONCLUSION: There was evidence that
      global changes in mindfulness are linked to better outcomes. This evidence
      pertained more to interventions targeting psychological rather than physical
      health conditions. While there is promising evidence that MBCT/MBSR intervention
      effects are mediated by hypothesised mechanisms, there is a lack of
      methodological rigour in the field of testing mechanisms of action for both MBCT
      and MBSR, which precludes definitive conclusions.

PMID- 28501709
TI  - Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic
      alternative for control of non-infectious uveitis.
AB  - : Supramolecular hydrogels formed by the self-assembly of therapeutic agents have
      received considerable attention due to their high drug payload and carrier-free
      features. Herein, we constructed a dexamethasone sodium phosphate (Dex)
      supramolecular hydrogel in combination with Dex and calcium ion (Ca2+) and
      further demonstrated its therapeutic efficacy in the control of ocular
      inflammation. The developed supramolecular hydrogel was thoroughly characterized
      by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked
      influence on the sol-gel transition behaviour of hydrogel and the proposed Dex
      supramolecular hydrogel displayed thixotropic properties. The drug release rate
      from Dex supramolecular hydrogel was dependent on the Ca2+ concentration. In
      comparison with Dex aqueous solution, single intravitreal injections of Dex
      supramolecular hydrogel up to 30MUg/eye were well tolerated without causing
      undesirable complications of fundus blood vessel tortuosity and lens opacity, as
      indicated by electroretinograms (ERGs), fundus photography and histopathology.
      Moreover, the administration by Dex supramolecular hydrogel exhibited a
      comparable anti-inflammatory efficacy to native Dex solution on an experimental
      autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the
      therapeutic efficacy had in a dosage-dependent manner. Histological observation
      and cytokines measurements indicated that both Dex solution and Dex
      supramolecular hydrogel (30MUg/eye) treatment could significantly attenuate the
      inflammatory response in both anterior and posterior chambers via the
      downregulation of Th1 and Th17 effector responses. All these data suggested that
      the developed Dex supramolecular hydrogel might be a therapeutic alternative for
      non-infectious uveitis with minimal risk of the induction of lens opacity and
      fundus blood vessel tortuosity. STATEMENT OF SIGNIFICANCE: A facile ionic cross
      linking strategy was exploited to construct a dexamethasone sodium phosphate
      (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal
      injection of Dex hydrogel displayed excellent intraocular biocompatibility
      without causing the complications of fundus blood vessel tortuosity and lens
      opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti
      inflammatory response to native Dex formulation on an experimental autoimmune
      uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses.

PMID- 28501710
TI  - Carbon nanotube, graphene and boron nitride nanotube reinforced bioactive
      ceramics for bone repair.
AB  - : The high brittleness and low strength of bioactive ceramics have severely
      restricted their application in bone repair despite the fact that they have been
      regarded as one of the most promising biomaterials. In the last few years, low
      dimensional nanomaterials (LDNs), including carbon nanotubes, graphene and boron
      nitride nanotubes, have gained increasing attention owing to their favorable
      biocompatibility, large surface specific area and super mechanical properties.
      These qualities make LDNs potential nanofillers in reinforcing bioactive
      ceramics. In this review, the types, characteristics and applications of the
      commonly used LDNs in ceramic composites are summarized. In addition, the
      fabrication methods for LDNs/ceramic composites, such as hot pressing, spark
      plasma sintering and selective laser sintering, are systematically reviewed and
      compared. Emphases are placed on how to obtain the uniform dispersion of LDNs in
      a ceramic matrix and maintain the structural stability of LDNs during the high
      temperature fabrication process of ceramics. The reinforcing mechanisms of LDNs
      in ceramic composites are then discussed in-depth. The in vitro and in vivo
      studies of LDNs/ceramic in bone repair are also summarized and discussed.
      Finally, new developments and potential applications of LDNs/ceramic composites
      are further discussed with reference to experimental and theoretical studies.
      STATEMENT OF SIGNIFICANCE: Despite bioactive ceramics having been regarded as
      promising biomaterials, their high brittleness and low strength severely restrict
      their application in bone scaffolds. In recent years, low-dimensional
      nanomaterials (LDNs), including carbon nanotubes, graphene and boron nitride
      nanotubes, have shown great potential in reinforcing bioactive ceramics owing to
      their unique structures and properties. However, so far it has been difficult to
      maintain the structural stability of LDNs during fabrication of LDNs/ceramic
      composites, due to the lengthy, high-temperature process involved. This review
      presents a comprehensive overview of the developments and applications of LDNs in
      bioactive ceramics. The newly-developed fabrication methods for LDNs/ceramic
      composites, the reinforcing mechanisms and the in vitro and in vivo performance
      of LDNs are also summarized and discussed in detail.

PMID- 28501708
TI  - Responsiveness and Minimally Important Differences for 4 Patient-Reported
      Outcomes Measurement Information System Short Forms: Physical Function, Pain
      Interference, Depression, and Anxiety in Knee Osteoarthritis.
AB  - : Patient-Reported Outcomes Measurement Information System (PROMIS) instruments
      can provide valid, interpretable measures of health status among adults with
      osteoarthritis (OA). However, their ability to detect meaningful change over time
      is unknown. We evaluated the responsiveness and minimally important differences
      (MIDs) for 4 PROMIS Short Forms: Physical Function, Pain Interference,
      Depression, and Anxiety. We analyzed adults with symptomatic knee OA from our
      randomized trial comparing Tai Chi and physical therapy. Using baseline and 12
      week scores, responsiveness was evaluated according to consensus standards by
      testing 6 a priori hypotheses of the correlations between PROMIS and legacy
      change scores. Responsiveness was considered high if >=5 hypotheses were
      confirmed, and moderate if 3 or 4 were confirmed. MIDs were evaluated according
      to prospective change for people achieving previously-established MID on legacy
      comparators. The lowest and highest MIDs meeting a priori quality criteria formed
      a MID range for each PROMIS Short Form. Among 165 predominantly female (70%) and
      white (57%) participants, mean age was 61 years and body mass index was 33.
      PROMIS Physical Function had 5 confirmed hypotheses and Pain Interference,
      Depression, and Anxiety had 3 or 4. MID ranges were: Depression = 3.0 to 3.1;
      Anxiety = 2.3 to 3.4; Physical Function = 1.9 to 2.2; and Pain Interference =
      2.35 to 2.4. PROMIS Physical Function has high responsiveness, and Depression,
      Anxiety, and Pain Interference have moderate responsiveness among adults with
      knee OA. We established the first MIDs for PROMIS in this population, and
      provided an important standard of reference to better apply or interpret PROMIS
      in future trials or clinical practice. PERSPECTIVE: This study examined whether
      PROMIS Short Form instruments (Physical Function, Pain Interference, Depression,
      and Anxiety) were able to detect change over time among adults with knee OA, and
      provided minimally important change estimates for each measure. This standard of
      reference can help apply or interpret these instruments in the future.

PMID- 28501711
TI  - Protection of cortex by overlying meninges tissue during dynamic indentation of
      the adolescent brain.
AB  - : Traumatic brain injury (TBI) has become a recent focus of biomedical research
      with a growing international effort targeting material characterization of brain
      tissue and simulations of trauma using computer models of the head and brain to
      try to elucidate the mechanisms and pathogenesis of TBI. The meninges, a
      collagenous protective tri-layer, which encloses the entire brain and spinal cord
      has been largely overlooked in these material characterization studies. This has
      resulted in a lack of accurate constitutive data for the cranial meninges,
      particularly under dynamic conditions such as those experienced during head
      impacts. The work presented here addresses this lack of data by providing for the
      first time, in situ large deformation material properties of the porcine dura
      arachnoid mater composite under dynamic indentation. It is demonstrated that this
      tissue is substantially stiffer (shear modulus, MU=19.10+/-8.55kPa) and relaxes
      at a slower rate (tau1=0.034+/-0.008s, tau2=0.336+/-0.077s) than the underlying
      brain tissue (MU=6.97+/-2.26kPa, tau1=0.021+/-0.007s, tau2=0.199+/-0.036s),
      reducing the magnitudes of stress by 250% and 65% for strains that arise during
      indentation-type deformations in adolescent brains. STATEMENT OF SIGNIFICANCE: We
      present the first mechanical analysis of the protective capacity of the cranial
      meninges using in situ micro-indentation techniques. Force-relaxation tests are
      performed on in situ meninges and cortex tissue, under large strain dynamic micro
      indentation. A quasi-linear viscoelastic model is used subsequently, providing
      time-dependent mechanical properties of these neural tissues under loading
      conditions comparable to what is experienced in TBI. The reported data highlights
      the large differences in mechanical properties between these two tissues. Finite
      element simulations of the indentation experiments are also performed to
      investigate the protective capacity of the meninges. These simulations show that
      the meninges protect the underlying brain tissue by reducing the overall
      magnitude of stress by 250% and up to 65% for strains.

PMID- 28501712
TI  - 3D bioprinting for drug discovery and development in pharmaceutics.
AB  - : Successful launch of a commercial drug requires significant investment of time
      and financial resources wherein late-stage failures become a reason for
      catastrophic failures in drug discovery. This calls for infusing constant
      innovations in technologies, which can give reliable prediction of efficacy, and
      more importantly, toxicology of the compound early in the drug discovery process
      before clinical trials. Though computational advances have resulted in more
      rationale in silico designing, in vitro experimental studies still require
      gaining industry confidence and improving in vitro-in vivo correlations. In this
      quest, due to their ability to mimic the spatial and chemical attributes of
      native tissues, three-dimensional (3D) tissue models have now proven to provide
      better results for drug screening compared to traditional two-dimensional (2D)
      models. However, in vitro fabrication of living tissues has remained a bottleneck
      in realizing the full potential of 3D models. Recent advances in bioprinting
      provide a valuable tool to fabricate biomimetic constructs, which can be applied
      in different stages of drug discovery research. This paper presents the first
      comprehensive review of bioprinting techniques applied for fabrication of 3D
      tissue models for pharmaceutical studies. A comparative evaluation of different
      bioprinting modalities is performed to assess the performance and ability of
      fabricating 3D tissue models for pharmaceutical use as the critical selection of
      bioprinting modalities indeed plays a crucial role in efficacy and toxicology
      testing of drugs and accelerates the drug development cycle. In addition,
      limitations with current tissue models are discussed thoroughly and future
      prospects of the role of bioprinting in pharmaceutics are provided to the reader.
      STATEMENT OF SIGNIFICANCE: Present advances in tissue biofabrication have crucial
      role to play in aiding the pharmaceutical development process achieve its
      objectives. Advent of three-dimensional (3D) models, in particular, is viewed
      with immense interest by the community due to their ability to mimic in vivo
      hierarchical tissue architecture and heterogeneous composition. Successful
      realization of 3D models will not only provide greater in vitro-in vivo
      correlation compared to the two-dimensional (2D) models, but also eventually
      replace pre-clinical animal testing, which has their own shortcomings. Amongst
      all fabrication techniques, bioprinting- comprising all the different modalities
      (extrusion-, droplet- and laser-based bioprinting), is emerging as the most
      viable fabrication technique to create the biomimetic tissue constructs.
      Notwithstanding the interest in bioprinting by the pharmaceutical development
      researchers, it can be seen that there is a limited availability of comparative
      literature which can guide the proper selection of bioprinting processes and
      associated considerations, such as the bioink selection for a particular
      pharmaceutical study. Thus, this work emphasizes these aspects of bioprinting and
      presents them in perspective of differential requirements of different
      pharmaceutical studies like in vitro predictive toxicology, high-throughput
      screening, drug delivery and tissue-specific efficacies. Moreover, since
      bioprinting techniques are mostly applied in regenerative medicine and tissue
      engineering, a comparative analysis of similarities and differences are also
      expounded to help researchers make informed decisions based on contemporary
      literature.

PMID- 28501714
TI  - Determination of polymer crystallinity by the multivariable curve resolution
      method in 13C solid NMR spectrum.
AB  - Most of the polymers are composed of a crystal part, an amorphous part, and a
      transitional interfacial part. These components present disparate physical and
      chemical characteristics. However, it always suffers from peak overlapping in
      solid NMR spectrum in order to acquire polymer's crystallinity. The polyethylene
      oxide (PEO) sample was tested using the Torchia pulse sequence combined with the
      Multivariate Curve Resolution (MCR) method. A two dimensional CP/MAS spectrum
      containing spin-lattice relaxation time (T1) information was acquired. After the
      correction based on the reciprocity relation, the overlapped peaks were resolved
      and quantified together with their T1's. Crystallinity is therefore observed
      naturally according to components' content ratios associated with their T1
      values.

PMID- 28501713
TI  - An in situ photocrosslinkable platelet rich plasma - Complexed hydrogel glue with
      growth factor controlled release ability to promote cartilage defect repair.
AB  - : The repair of articular cartilage injury is a great clinical challenge.
      Platelet-rich plasma (PRP) has attracted much attention for the repair of
      articular cartilage injury, because it contains various growth factors that are
      beneficial for wound repair. However, current administration methods of PRP have
      many shortcomings, such as unstable biological fixation and burst release of
      growth factors, all of which complicate its application in the repair of
      articular cartilage and compromise its therapeutic efficacy. In this study, based
      on our previously reported photoinduced imine crosslinking (PIC) reaction, we
      developed an in situ photocrosslinkable PRP hydrogel glue (HNPRP) through adding
      a photoresponsive hyaluronic acid (HA-NB) which could generate aldehyde groups
      upon light irradiation and subsequently react with amino groups, into autologous
      PRP. Our study showed that HNPRP hydrogel glue was cytocompatible and could be
      conveniently and rapidly prepared in situ, forming a robust hydrogel scaffold. In
      addition, our results demonstrated that HNPRP hydrogel not only achieved
      controlled release of growth factors, but also showed strong tissue adhesive
      ability. Therefore, HNPRP hydrogel was quite suitable for cartilage defect
      regeneration. Our further in vitro experiment showed that HNPRP hydrogel could
      promote the proliferation and migration of chondrocytes and bone marrow stem
      cells (BMSCs). In vivo testing using a rabbit full-thickness cartilage defect
      model demonstrated that HNPRP hydrogel could achieve integrative hyaline
      cartilage regeneration and its therapeutic efficacy was better than thrombin
      activated PRP gel. STATEMENT OF SIGNIFICANCE: In this study, we have developed a
      photocrosslinkable platelet rich plasma (PRP) - complexed hydrogel glue (HNPRP)
      for cartilage regeneration. The in situ formed HNPRP hydrogel glue showed not
      only the controlled release ability of growth factors, but also strong tissue
      adhesiveness, which could resolve the current problems in clinical application of
      PRP. Furthermore, HNPRP hydrogel glue could promote integrative hyaline cartilage
      regeneration, and its reparative efficacy for cartilage defect was better than
      thrombin activated PRP gel. This study provided not only an effective repair
      material for cartilage regeneration, but also developed an advanced method for
      PRP application.

PMID- 28501716
TI  - Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A
      comparative conformational analysis.
AB  - The capsular polysaccharide is the main virulence factor in meningococcus. The
      capsular polysaccharides for meningococcal serogroups Y and W are almost
      identical polymers of hexose-sialic acid, suggesting the possibility of cross
      protection between group Y and W vaccines. However, early studies indicated that
      they elicit different levels of cross-protection. Here we explore the
      conformations of the meningococcal Y and W polysaccharides with molecular
      dynamics simulations of three repeating unit oligosaccharide strands. We find
      differences in Y and W antigen conformation: the Y polysaccharide has a single
      dominant conformation, whereas W exhibits a family of conformations including the
      Y conformation. This result is supported by our NMR NOESY analysis, which
      indicates key close contacts for W that are not present in Y. These
      conformational differences provide an explanation for the different levels of
      cross-protection measured for the Y and W monovalent vaccines and the high group
      W responses observed in HibMenCY-TT vaccinees.

PMID- 28501715
TI  - Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate
      of Haemonchus contortus.
AB  - Resistance to the anthelmintic drug monepantel (Zolvix(r)) has emerged in
      parasitic worms infecting sheep and goats. The mechanism of resistance in these
      cases is unknown. The drug targets nicotinic acetylcholine receptors belonging to
      the nematode-specific DEG-3 subfamily. We examined the receptor gene, Hco-mptl-1,
      in a highly Zolvix(r)-resistant and a -susceptible isolate of the parasitic
      nematode Haemonchus contortus. cDNA coding for the full length receptor protein
      (Hco-MPTL-1) was present in all clones prepared from a pool of susceptible larvae
      (21/21 clones) and approximately 50% of those from the resistant isolate (17/33).
      On the other hand, the remaining clones from the resistant isolate showed various
      mutations that resulted in truncated predicted proteins, missing at least one
      transmembrane domain. The most common mutation (11/33 clones) resulted in the
      retention of intron 15, a premature stop codon, and a truncated protein.
      Sequencing of intron 15 genomic DNA showed very few SNPs in susceptible larvae
      and in 12/18 clones from resistant larvae, alongside the presence of at least 17
      SNPs in the remaining resistant clones. The present study shows that the highly
      resistant isolate has a number of mutations in the drug target gene that would
      most-likely result in a non-functional receptor, thus rendering the larvae
      insensitive to the drug. The presence of many wild-type sequences in this highly
      resistant population suggests that there was a significant presence of
      heterozygotes in the survivors of the field drench treatment from which the
      isolate was derived, and hence that at least some of the mutations may be
      dominant. Alternatively, their presence may be due to the additional influence of
      mutations at another locus contributing to the resistance phenotype. The presence
      of multiple separate mutations in the Hco-mptl-1 gene in this viable field
      derived worm isolate may at least partly explain why resistance to Zolvix(r) has
      arisen rapidly in the field.

PMID- 28501717
TI  - Assisting asylum seekers in a time of global forced displacement: Five clinical
      cases.
AB  - According to the United Nations High Commissioner on Refugees, over 65 million
      people were displaced from their homes due to conflict and persecution in 2015.
      Many physicians express an interest in human rights and a desire to assist this
      group of refugees and asylum seekers. Physicians are able to use their unique
      skills by performing medical forensic evaluations of individuals seeking asylum.
      Some asylum seekers have psychological or physical scars or functional
      abnormalities relating to injuries or ill-treatment they experience due to
      persecution. Documenting these findings can significantly improve the likelihood
      that they will be granted asylum. This manuscript outlines the historical and
      legal background of asylum. Each of the individuals presented in this paper
      experienced persecution in different forms. One person was tortured due to his
      political opinion and one was assaulted because he was gay. One woman sought
      asylum due to domestic violence, another woman because she had been subjected to
      female genital mutilation/cutting (FGM/C) and the last suffered severe
      psychological trauma related to a forced marriage. Five typical clinical cases of
      medical forensic evaluations are outlined, each with different forms of
      persecution and physical or psychological findings. Physicians have an interest
      in using their expertise to help this underserved population. They report that
      working with asylum seekers is rewarding, intellectually stimulating and a novel
      way to use their training and skills.

PMID- 28501718
TI  - Luminescence studies of zinc borates activated with different concentrations of
      Ce and La under x-ray and electron excitation.
AB  - Several ZnB2O4 powder samples having dopants concentrations of 0.1, 0.01, 0.04wt%
      Ce and La were prepared using the nitric acid method via the starting oxides.
      Several complementary methods such as powder X-ray diffraction (XRD), thermal
      analyses environmental scanning electron microscopy (ESEM), Radioluminescence
      (RL) and Cathodoluminescence (CL) techniques were used. Unique luminescence
      properties of Ce doped ZnB2O4 powder samples are reported for the first time. A
      new luminescence bands appearing in red part of the spectrum and having all the
      characteristics of Ce3+ were obtained from RL results. Changing the Ce and La
      concentration of 0.01-0.1wt% leads to an increase in RL and CL intensities of
      Ce3+ and La3+ ions and also CL emission spectra of ZnB2O4 show gradual shift
      towards longer wavelength. When we compare the luminescence intensity of the
      samples it is seen that Ce doped ZnB2O4 has the highest intense whereas La doped
      ZnB2O4 has the lowest one. However, emission spectra of both Ce and La doped
      samples kept unchanged.

PMID- 28501719
TI  - Colliding jets provide depth control for water jetting in bone tissue.
AB  - In orthopaedic surgery, water jet drilling provides several advantages over
      classic drilling with rigid drilling bits, such as the always sharp cut, absence
      of thermal damage and increased manoeuvrability. Previous research showed that
      the heterogeneity of bone tissue can cause variation in drilling depth whilst
      water jet drilling. To improve control over the drilling depth, a new method is
      tested consisting of two water jets that collide directly below the bone surface.
      The expected working principle is that after collision the jets will
      disintegrate, with the result of eliminating the destructive power of the
      coherent jets and leaving the bone tissue underneath the focal point intact. To
      assess the working principle of colliding water jets (CWJ), the influence of
      inhomogeneity of the bone tissue on the variation of the drilling depth and the
      impact of jet time (twj) on the drilling depth were compared to a single water
      jet (SWJ) with a similar power. 98 holes were drilled in 14 submerged porcine
      tali with two conditions CWJ (impact angle of 30 degrees  and 90 degrees ) and
      SWJ. The water pressure was 70MPa for all conditions. The water jet diameter was
      0.3 mm for CWJ and 0.4 mm for SWJ. twj was set at 1, 3, 5 and 8s. Drilling depth
      and hole diameter were measured using microCT scans. A non-parametric Levene's
      test was performed to assess a significant difference in variance between
      conditions SWJ and CWJ. A regression analysis was used to determine differences
      in influence of twj on the drilling depth. Hole diameter differences were
      assessed using a one way Anova. A significance level of p<0.05 was set. Condition
      CWJ significantly decreases the drilling depth variance caused by the
      heterogeneity of the bone when compared to SWJ. The mean depth for CWJ was 0.9 mm
      (SD 0.3 mm) versus 4.8 mm (SD 2.0) for SWJ. twj affects the drilling depth less
      for condition CWJ (p<0.01, R2=0.30) than for SWJ (p<0.01, R2=0.46). The impact
      angle (30 degrees  or 90 degrees ) of the CWJ does not influence the drilling
      depth nor the variation in depth. The diameters of the resulting holes in the
      direction of the jets is significantly larger for CWJ at 90 degrees  than for 30
      degrees  or a single jet. This study shows that CWJ provides accurate depth
      control when water jet drilling in an inhomogeneous material such as bone. The
      maximum variance measured by using the 95% confidence interval is 0.6 mm opposed
      to 5.4 mm for SWJ. This variance is smaller than the accuracy required for bone
      debridement treatments (2-4 mm deep) or drilling pilot holes. This confirms that
      the use of CWJ is an inherently safe method that can be used to accurately drill
      in bones.

PMID- 28501720
TI  - Characterization and restoration of degenerated IVD function with an injectable,
      in situ gelling alginate hydrogel: An in vitro and ex vivo study.
AB  - Intervertebral disc (IVD) degeneration is a naturally, irreparable process that
      causes loss in IVD hydration, cellularity, and, mechanical stability. Invasive
      surgical attempts to ease back pain and, radiculopathy have shown to cause
      increased degeneration along the rest, of the spine. Due to its highly tunable
      mechanical and degradation, properties, alginate is a viable option for a less
      invasive injectable, repair for IVD degeneration. This study centers on the
      characterization, of in situ gelling alginate and subsequent injection into
      enzymatically, degraded motion segments., In situ gelation of 2% alginate (% w/v
      PBS) was performed using calcium, carbonate (CaCO3) and glucono-delta-lactone
      (GDL) and compared to, instantaneously gelled 2% alginate crosslinked with
      calcium chloride., After characterization of multiple molar concentrations, a
      ratio of, 60mM:120mM CaCO3:GDL was determined to have the most optimum
      properties, for injection. Enzymatically degraded bovine caudal motion segments
      were, injected with the optimized in situ gelling alginate and mechanically,
      loaded; injected motion segments were compared to intact specimens, degraded
      specimens, and specimens injected with 20% gelatin to, corroborate with previous
      ex vivo injection studies., Overall, injection of in situ curing 2% alginate into
      an enzymatically, and mechanically degraded IVD restores function via reduction
      of height, loss over long-term cyclic loading, is constrained within the disc
      with, no injection site leakage, and successfully fills all void spaces created,
      by chemonucleolysis with 1% collagenase-f. These findings, along with the,
      ability of alginate to be specifically tailored to support cell, viability, show
      promise for a tissue engineered injectable NP substitute for the reversal of disc
      degeneration.

PMID- 28501721
TI  - Cortical bone elasticity measured by resonant ultrasound spectroscopy is not
      altered by defatting and synchrotron X-ray imaging.
AB  - In the study of mechanical properties of human bone, specimens may be defatted
      before experiments to prevent contamination and the risk of infections. High
      energy synchrotron radiation micro-computed tomography (SR-MUCT) is a popular
      technique to study bone microstructure. However, little is known about the
      effects of defatting or irradiation during SR-MUCT imaging on different elastic
      coefficients including shear and longitudinal moduli in different anatomical
      directions. In this work, these effects are evaluated on a set of 24 samples
      using resonant ultrasound spectroscopy (RUS), which allows one to accurately
      measure the complete set of elastic coefficients of cortical bone non
      destructively. The results show that defatting with diethylether and methanol and
      irradiation up to 2.5kGy has no detectable effect on any of the elastic
      coefficients of human cortical bone.

PMID- 28501722
TI  - Spatial QRS-T angle in patients with newly diagnosed obstructive sleep apnea
      syndrome.
AB  - PURPOSE: The aim of the study was to assess the spatial QRS-T angle (QRS-TA) in a
      group of newly diagnosed and untreated adult patients with obstructive sleep
      apnea syndrome (OSAS) and to identify potential factors affecting this parameter.
      PATIENTS AND METHODS: The study group (PSG-confirmed OSAS) included 62
      individuals, aged 51.7+/-10.3 years. The control group consisted of 25
      individuals, aged 46.6+/-16.6 years with no sleep-disordered breathing. The
      diagnosis of OSAS and assessment of its severity was based on unattended all
      night screening polysomnography. The spatial QRS-TA was reconstructed from 12
      lead ECG using Kors' regression method. RESULTS: Significant differences of
      spatial QRS-TA values were found between patients with severe OSAS (36.9+/-18.9
      degrees ) and the controls (20.3+/-13.4 degrees ; p<0.01) and between patients
      with mild or moderate OSAS (32.3+/-20.1 degrees ) and the controls (p=0.01).
      Statistically significant correlations were found between spatial QRS-TA and
      polysomnographic indices (i.e. AHI, AI, RDT and RDTI). CONLUSIONS: Spatial QRS-TA
      values are significantly higher in patients with OSAS than in controls, thus
      indicating increased heterogeneity of myocardial action potential. Further long
      term prospective studies evaluating the prognostic value of spatial QRS-TA in
      OSAS patients are needed.

PMID- 28501723
TI  - Tangeretin alters neuronal apoptosis and ameliorates the severity of seizures in
      experimental epilepsy-induced rats by modulating apoptotic protein expressions,
      regulating matrix metalloproteinases, and activating the PI3K/Akt cell survival
      pathway.
AB  - PURPOSE: Epilepsy is complex neural disarray categorized by recurring seizures.
      Despite recent advances in pharmacotherapies for epilepsy, its treatment remains
      a challenge due to the contrary effects of the drugs. As a result, the
      identification of novel anti-epileptic drugs (AEDs) with neuroprotective
      properties and few side effects is of great value. Thus, the present study
      assessed the treatment effects of tangeretin using a rat model of pilocarpine
      induced epilepsy. MATERIALS AND METHODS: Separate groups of male Wistar rats
      received oral administrations of tangeretin at 50, 100, or 200mg/kg for 10 days
      and then, on the 10th day, they received an intraperitoneal injection of
      pilocarpine (30mg/kg). Subsequently, neuronal degeneration and apoptosis were
      assessed using Nissl staining and terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP nick end labeling (TUNEL) assay procedures. Additionally, the
      expressions of phosphatidylinositol-3-kinase (PI3K/Akt) pathway proteins, cleaved
      caspase-3, Bad, Bcl-2, Bcl-xL, and Bax were determined using Western blot
      analyses. RESULTS: Tangeretin reduced the seizure scores and latency to first
      seizure of the rats and effectively activated the pilocarpine-induced suppression
      of PI3K/Akt signaling. Additionally, tangeretin effectively regulated the levels
      of apoptosis-inducing factor (AIF) in mitochondria as well as the expressions of
      apoptotic pathway proteins. Seizure-induced elevations in the activities and
      expressions of matrix metalloproteinases (MMPs)-2 and -9 were also modulated.
      CONCLUSION: The present results indicate that tangeretin exerted potent
      neuroprotective effects against pilocarpine-induced seizures via the activation
      of PI3K/Akt signaling and the regulation of MMPs.

PMID- 28501724
TI  - Different manifestations of pulmonary embolism in younger compared to older
      patients: Clinical presentation, prediction rules and long-term outcomes.
AB  - PURPOSE: Data concerning specific manifestations of pulmonary embolism (PE) among
      younger patients are scarce. We aimed to evaluate differences in clinical
      presentation, PE prediction rules, thrombolytic treatment use and PE outcomes in
      younger (<50 years of age) compared to older patients. MATERIAL/METHODS: We
      studied 238 consecutive patients with proven PE who were retrospectively
      categorized into three PE probability subgroups according to the revised Geneva
      score (RGS) and Wells score (WS). Duration of follow-up was up to 115 months.
      RESULTS: Younger patients accounted for 19.7% of the study cohort. Obesity and
      smoking were significantly more common, while comorbidities were less common
      (P<0.05) in the younger patients. According to RGS and WS, younger patients were
      more often categorized into the low PE probability subgroup and rarely into the
      high probability subgroup (P<0.05). We found no differences in clinical signs,
      symptoms, and treatment between the two groups. In-hospital (2% vs. 13%) and long
      term (12% vs. 36%) mortality rates were significantly lower in younger patients
      (P=0.003). CONCLUSIONS: In younger PE patients, despite differences in
      predisposing factors and PE probability grading as assessed by RGS and WS,
      clinical features at admission and treatment were similar compared to the older
      group. Our findings confirmed lower mortality among younger compared to older
      patients.

PMID- 28501725
TI  - A device for testing the durability and exploitation reliability of dental
      prostheses.
AB  - PURPOSE: The aim of this work was to develop the design of the construction of a
      stand for testing the operational stability of dental prostheses, designed on the
      basis of an own idea. There are no devices that would make it possible to test
      complete structures, including the actual kinematics of motion and the influence
      of the environment of the oral cavity. MATERIALS AND METHODS: Presented were
      several devices used for testing both fixed and removable prostheses. Attention
      was paid to their limited possibilities in the area of the tested friction node,
      kinematics of motion, and the assessment of the influence of the environment of
      the oral cavity on the tested functional quality. The construction was based on
      the author's own ideas as well as on a review of the available literature.
      RESULTS: As the final result of the research, simplified images of the stand were
      presented along with their descriptions. CONCLUSIONS: The experimental
      verification of the stand allowed concluding that the research aims have been
      achieved. First of all, the device allows testing prosthetic structures of
      different sizes and it is possible to load the tested prostheses in randomly
      chosen points.

PMID- 28501726
TI  - Osteogenic differentiation of mesenchymal stem cells is impaired by bone
      morphogenetic protein 7.
AB  - PURPOSE: Mesenchymal stem cells (MSCs) are multipotent adult stem cells and
      present in practically all tissues but originally identified within the bone
      marrow (BM). The differentiation potential of these cells is generally impaired
      when culturing in vitro for cell expansion. The aim of this study is to speedily
      increase the numbers of bone marrow derived mesenchymal stem cells (BM-MSCs) with
      substantially maintaining their differentiation potential in vitro and improving
      bone formation in vivo. MATERIALS AND METHODS: BM-MSCs isolated from rats were
      sequentially cultured in alpha-MEM containing basic fibroblast growth factor
      (FGF2) and/or insulin to stimulate proliferation and osteogenic commitment, and
      in the medium with the addition of bone morphogenetic protein 2 (BMP2) and/or
      bone morphogenetic protein 7 (BMP7) to arouse differentiation. The expression of
      genes markedly associating the commitment and differentiation were investigated
      in vitro using real-time PCR technique and mineralization assay, while the
      capacity of inducing bone formation by the established conditions was determined
      in vivo using a rat model. RESULTS: The BM-MSCs greatly proliferated with active
      transcription of runx2 and osterix genes when induced by FGF2 and insulin. The in
      vitro mineralization was enhanced by BMP2, but the extent was diminished when
      BMP2 was replaced or supplemented by BMP7. Formation of new small blood vessels
      was notably detected when the cells were respectively challenged by FGF2 plus
      insulin and BMP2. CONCLUSION: These data are valuable in choosing growth factors
      for proper bone repair. However, optimization of the established system would be
      essential when the cells of human source are applied.

PMID- 28501727
TI  - Methods to evaluate arterial structure and function in children - State-of-the
      art knowledge.
AB  - BACKGROUND: With increasing rates of hypertension, obesity, and diabetes in the
      pediatric population, wide available, and reproducible methods are necessary to
      evaluate arterial structure and function in children and adolescents. METHODS:
      MEDLINE/Pubmed was searched for articles published in years 2012-2017 on
      methodology of, current knowledge on, and limitations of the most commonly used
      methods to evaluate central, proximal and coronary arteries, as well as
      endothelial function in pediatric patients. RESULTS: Among 1528 records screened
      (including 1475 records from years 2012 to 2017) 139 papers were found suitable
      for the review. Following methods were discussed in this review article:
      ultrasound measurements of the intima-media thickness, coronary calcium scoring
      using computed tomography, arterial stiffness measurements (pulse wave velocity
      and pulse wave analysis, carotid artery distensibility, pulse pressure, and
      ambulatory arterial stiffness index), ankle-brachial index, and methods to
      evaluate vascular endothelial function (flow-mediated vasodilation, peripheral
      arterial tonometry, Doppler laser flowmetry, and cellular and soluble markers of
      endothelial dysfunction). CONCLUSIONS: Ultrasonographic measurement of carotid
      intima-media thickness and measurement of pulse wave velocity (by oscillometry or
      applanation tonometry) are highly reproducible methods applicable for both
      research and clinical practice with proved applicability for children aged >=6
      years or with height >=120cm. Evaluation of ambulatory arterial stiffness index
      by ambulatory blood pressure monitoring is another promising option in pediatric
      high-risk patients. Clearly, further studies are necessary to evaluate usefulness
      of these and other methods for the detection of subclinical arterial damage in
      children.

PMID- 28501728
TI  - Effects of fine air particulates on gene expression in non-small-cell lung
      cancer.
AB  - PURPOSE: Airborne particulate matter smaller than 2.5MUm (PM2.5) has been shown
      to induce adverse health effects through various mechanisms. However, its effects
      on gene expression in non-small-cell lung cancer (NSCLC) remain undefined. The
      aim of this study was to analyze the expression profile of PM2.5-induced adverse
      health effects on human. MATERIALS AND METHODS: We performed RNA sequencing to
      elucidate key molecular effects of PM2.5 collected from Shenyang China, to
      identify potential diagnostic markers or therapeutic targets, and further
      validated these differences in gene expression by using quantitative PCR in A549
      and H1299 human non-small-cell lung cancer cell lines. To investigate the
      functional changes on PM2.5 exposed cells, we carried out the viability assay for
      the cell counting, and the Boyden chamber assay for invasion. RESULTS: We found
      143 genes that were expressed at least twice as much, or no more than half as
      much, in NSCLC cells exposed to PM2.5 than in unexposed cells. Results showed
      deregulated genes confronted PM2.5 exposure were significantly expressed, but
      commonly expressed in NSCLC cells. In addition, according to the viability assay
      and the Boyden chamber assay, PM2.5 exposed cells which have more competent on
      proliferation and invasion can keep the line with the results in RNA-Seq.
      CONCLUSION: Our data may provide a more specific understanding of the signaling
      patterns associated with pathogenesis, and lead to novel markers and therapeutic
      targets for NSCLC.

PMID- 28501729
TI  - Mulberry leaf extract decreases digestion and absorption of starch in healthy
      subjects-A randomized, placebo-controlled, crossover study.
AB  - PURPOSE: Mulberry (Morus alba L.) leaf tea has recently received much attention
      as a dietary supplement due to the wide range of putative health benefits, such
      as antidiabetic effects. Nevertheless, data evaluating its influence on
      carbohydrate metabolism in humans are scarce. The present study aims to
      investigate the effect of mulberry leaf extract supplementation on starch
      digestion and absorption in humans. MATERIALS AND METHODS: The study comprised of
      25 healthy subjects, aged 19-27 years. In all subjects, a starch 13C breath test
      was performed twice in a crossover and single blind design. Subjects were
      initially randomized to ingest naturally 13C-abundant cornflakes (50g
      cornflakes+100ml low fat milk) either with the mulberry leaf extract (36mg of
      active component-1-deoxynojirimycin) or the placebo and each subject received the
      opposite preparation one week later. RESULTS: The cumulative percentage dose
      recovery was lower for the mulberry leaf extract test than for the placebo test
      (median [quartile distribution]: 13.9% [9.9-17.4] vs. 17.2% [13.3-20.6];
      p=0.015). A significant decrease was detectable from minute 120 after the
      ingestion. CONCLUSIONS: A single dose of mulberry leaf extract taken with a test
      meal decreases starch digestion and absorption. These findings could possibly be
      translated into everyday practice for improvement of postprandial glycemic
      control.

PMID- 28501730
TI  - Larvicidal activity of vegetable oils and esterified compounds against Culex
      quinquefasciatus (Diptera: Culicidae).
AB  - Control of Culex quinquefasciatus using chemical insecticides may result in the
      selection of resistant mosquito strains. Thus, the use of plant-derived products
      has been studied as alternative for the mosquito control. Fatty acid methyl
      esters (FAMEs) obtained by transesterification of vegetable oils may result in
      compounds with larvicidal potential against C. quinquefasciatus. However, little
      is known about the morphological, physiological or biochemical effects that these
      FAMEs may have on mosquito larvae. The present study reports the effects of these
      FAMEs in mosquito larvae. The FAMEs were obtained by transesterification of
      canola, corn, sunflower, and soybean oils with acid catalysis and the
      determination of FAMEs composition was done by gas chromatography-mass
      spectrometry (GC-MS). Larvae of C. quinquefasciatus were exposed to different
      concentrations of the vegetable oils and FAMEs. Thereby, different FAMEs showed
      LC50 values ranging from 42.32 to 196.27mg/L against C. quinquefasciatus larvae.
      The methyl ester obtained from sunflower oil showed the lowest LC50. Histology of
      C. quinquefasciatus larvae exposed to LC50 of FAMEs was performed and changes in
      the midgut and fat body morphology were identified. Therefore, larval mortality
      and changes in the internal organs suggested that FAMEs might be a promising new
      class of larvicidalcompounds. Cytotoxicity of FAMEs compounds was assessed with
      the HeLa human cell line and no effect was observed.

PMID- 28501731
TI  - Learning and unlearning dignity in care: Experiential and experimental
      educational approaches.
AB  - Guarding against loss of human dignity is fundamental to nursing practice. It is
      assumed in the existing literature that 'dignity' as a concept and 'dignity in
      care' as a practice is amenable to education. Building on this assumption, a
      range of experiential and experimental educational approaches have been used to
      enhance students' understanding of dignity. However, little is known about
      student nurses' views on whether dignity is amenable to education and, if so,
      which educational approaches would be welcomed. This mixed-methods study used an
      online questionnaire survey and focus groups to address these questions. Student
      nurses in Scotland completed online questionnaires (n = 111) and participated in
      focus groups (n = 35). Students concluded that education has transformative
      potential to encourage learning around the concept of dignity and practice of
      dignity in care but also believed that dignity could be unlearned through
      repeated negative practice exposures. Experiential and experimental educational
      approaches were welcomed by student nurses, including patient testimony, role
      play, simulation, and empathy exercises to step into the lives of others. Nurse
      educators should further integrate experiential and experimental educational
      approaches into undergraduate and postgraduate nursing curricula to guard against
      the loss of learning around dignity students believed occurred over time.

PMID- 28501732
TI  - Asymmetrical stabilization and mobilization exploited during static single leg
      stance and goal directed kicking.
AB  - The motor control properties of the right and left legs are dependent on the
      stabilization and mobilization features of the motor tasks. The current
      investigation examined the right and left leg control differences - interlateral
      asymmetries - during static single leg stance and dynamic goal directed kicking
      with an emphasis of the asymmetrical stabilization and mobilization components of
      movements. Ten young, healthy, right-leg preferred individuals with minimal
      kicking experience completed both tests on each limb. During static single leg
      stance, participants were requested to stand as still as possible with one leg in
      contact with a force platform. Interlateral asymmetries of the standing leg were
      quantified using postural variability measures of the center of pressure (COP)
      standard deviation in the anterior-posterior (SD-COPAP) and medial-lateral (SD
      COPML) directions, resultant COP length and velocity, and 95% COP elliptical
      area. During dynamic goal directed kicking, participants stood on two adjacent
      force platforms in a side-by-side foot position and kicked a soccer ball toward
      three different directions as soon as they received an auditory cue of kicking.
      Three targets were located -30 degrees , 0 degrees  or 30 degrees  in front and
      3.05 m away from the participants' midline. Participants kicked the ball toward
      the targets with each of their feet. The vertical ground reaction force (vGRF) of
      the kicking leg was used to define the preparation (from above two standard
      deviations of vGRF baseline to toe-off) and swing (from toe-off to toe-return)
      phases of dynamic kicking. To determine the presence of interlateral asymmetries
      during dynamic kicking, the magnitude and timing of the anticipatory postural
      adjustments (APA) during the preparation phase of kicking were quantified using
      the lateral net COP (COPnet-ML) time series derived from both force platforms.
      Postural variability measures of the support leg and the kinematic joint range of
      motion (JROM) trajectories of the kicking leg were also used to examined
      interlateral asymmetries. During static stance, no between-leg significance was
      identified for all dependent measures of COP variability suggesting symmetrical
      stabilization. During the preparation phase of kicking, both right and left leg
      kicking exhibited a similar level of APA magnitude, although the left leg kicking
      was shown to reach its maximum APA magnitude earlier than the right leg. In the
      support leg role, the right leg showed greater COP variability in the ML
      direction as compared to the left support leg and greater COP variability was
      observed when kicking in the ipsilateral direction compared to the center and
      contralateral directions. For mobilization control, the left kicking leg showed
      greater JROM displacements at the distal (knee and ankle) joints and reduced JROM
      primarily with hip frontal plane movements compared to the right kicking leg. The
      reported interlateral asymmetries during kicking may reflect a behavioral
      adaptation that results in differential stabilization between the right and left
      legs. Overall, the findings suggest that novel tasks, such as dynamic goal
      directed kicking, appear to be more sensitive than static balance in identifying
      interlateral asymmetries.

PMID- 28501733
TI  - Insomnia in adult attention-deficit/hyperactivity disorder: A comparison with
      borderline personality disorder population in a clinical setting and control
      participants.
AB  - OBJECTIVES: Many adults with attention-deficit/hyperactivity disorder (ADHD)
      report sleeping difficulties. The relationship between sleep and ADHD is poorly
      understood, and shows discrepancies between subjective and objective measures. In
      order to determine the specificity of sleep-associated symptoms in ADHD,
      subjective sleep assessments among ADHD adult patients were compared with control
      subjects and with individuals suffering from borderline personality disorder
      (BPD). METHODS: 129 outpatients with ADHD, 70 with BPD (including 17 patients
      with BPD and ADHD comorbidity), and 65 control participants were assessed for
      sleep quality, insomnia, and sleepiness, using the Pittsburgh Sleep Quality Index
      (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale
      (ESS). RESULTS: ADHD- and BPD-sufferers achieved higher insomnia and lower sleep
      quality scores than control subjects. Clinical groups did not differ in terms of
      sleep quality, although insomnia was more severe among BPD patients. Depression
      scores explained most of sleep symptoms, but even when controlling for
      depression, ADHD sufferers showed higher sleep latency. Inattentive symptoms were
      associated with somnolence, while hyperactive/impulsive symptoms were associated
      with insomnia and lower sleep efficiency. CONCLUSION: Sleep-related symptoms
      associated with ADHD were partly explained by non-specific factors, especially
      depression symptoms. In a dimensional perspective, hyperactive and inattentive
      symptoms were associated with specific sleep symptoms.

PMID- 28501734
TI  - Social factors affect motor and anxiety behaviors in the animal model of
      attention-deficit hyperactivity disorders: A housing-style factor.
AB  - The present study examines whether housing style (e.g., single housing, same
      strain-grouped housing, and different-strain-grouped housing) and rat strain
      (e.g., spontaneous hypertension rats [SHR] and Wistar-Kyoto rats [WKY]) mediate
      motor function and anxiety behavior in the open field task. From week 4 through
      week 10 following birth, the rats were measured 30min for locomotor activity and
      anxiety once per week in the open field task. The SHR rats exhibited
      hyperactivity in total distance traveled and movement time to form the animal
      model of ADHD. The SHR rats spent more time inside the square and crossed the
      inside-outside line more often than the WKY rats, indicating the SHR rats
      exhibited less anxiety behavior. The different-strain-grouped housing style (but
      neither the same-strain-grouped housing style nor the single housing style)
      decreased total distance traveled and facilitated anxiety behavior. The motor
      function was negatively correlated with anxiety behavior for SHR rats but not for
      WKY rats. Housing styles had a negative correlation between motor function and
      anxiety behavior. The present findings provide some insights regarding how social
      factors (such as housing style) affect motor function and anxiety behavior
      related to ADHD in a clinical setting.

PMID- 28501735
TI  - Dose- and time-dependent effects of mirtazapine on the expression of cocaine
      induced behavioral sensitization in rats.
AB  - Relapse to cocaine use is a major problem in the clinical treatment of cocaine
      dependence. Antidepressant medications have been studied as potential therapeutic
      drugs to relieve a cocaine dependence disorder. Mirtazapine is an antidepressant
      implicated in reducing behavioral alterations induced by drugs of abuse. We have
      reported elsewhere that 30mg/kg mirtazapine administered for 30 days during
      cocaine extinction significantly attenuated the induction and expression of
      cocaine-induced locomotor sensitization and decreased the duration of the cocaine
      induced locomotor effect. This study focused on exploring whether different
      mirtazapine dosing regimens could optimize and/or improve the effect of 30mg/kg
      mirtazapine administered for 30 days on cocaine-induced locomotor activity during
      the expression phase of behavioral sensitization. Our study revealed that the
      daily dosing regimen with a fixed dose of mirtazapine (30mg/kg ip) over 60 days
      improved the decrease in cocaine-induced locomotor activity and behavioral
      sensitization obtained by dosing of 30mg mirtazapine for 30 days. In addition, it
      showed that a dosing regimen of 30mg/Kg mirtazapine for 30 days managed to reduce
      cocaine toxicity. These results suggested that dosage of mirtazapine for 30
      consecutive days may be an effective therapy.

PMID- 28501736
TI  - Role of IL-8, CRP and epidermal growth factor in depression and anxiety patients
      treated with mindfulness-based therapy or cognitive behavioral therapy in primary
      health care.
AB  - Epidermal growth factor (EGF) and inflammatory markers have been associated with
      various neuro-psychiatric disorders. However, their role in mild to moderate
      depression and anxiety patients treated with mindfulness-based group therapy
      (mindfulness) or cognitive behavioral therapy (CBT) is not known. In this study
      we analyzed plasma levels of interleukin (IL)-6, IL-8, high sensitivity C
      reactive protein (hsCRP) and EGF before (baseline) and after treatment (8 weeks)
      and investigated their role in response to both arms of the treatment. To cover
      variety of mental symptoms, treatment response was analyzed by four scales, the
      Montgomery-Asberg depression rating scale (MADRS), Hospital anxiety and
      depression scale- Depression (HADS-D) and anxiety (HADS-A) and patients health
      questionnaire-9. EGF levels were significantly decreased after both mindfulness
      and CBT and were associated with treatment response on all scales independent of
      the use of tranquilizers and antidepressant treatment. Moreover, baseline EGF
      levels were significantly associated only with baseline scores of anxiety scale.
      Levels of inflammatory markers analyzed in this study, were not significantly
      associated with treatment response on any scale. Our findings suggest that
      improvement in symptoms of depression and anxiety after both mindfulness and CBT
      is associated with changes in EGF levels but not with the inflammatory markers.

PMID- 28501738
TI  - Performance and psychometric properties of the Interpersonal Support Evaluation
      List (ISEL) in older adults with Complicated Grief.
AB  - BACKGROUND: Complicated Grief (CG) is a recently recognized bereavement-related
      mental health disorder. Social support is commonly measured with the
      Interpersonal Support Evaluation List (ISEL), a 40-item, 4-factor, self-report
      measure. Though the ISEL has been well-studied, no identified research has
      examined its psychometric properties or performance in older adults with CG.
      METHODS: We examined the psychometric properties of the ISEL in adults age >=60
      who enrolled in a psychotherapy treatment study for CG in New York City. We also
      examined the association of ISEL scores with CG severity, and with clinical and
      sociodemographic variables. RESULTS: Internal consistency of the ISEL was high
      (alpha=0.95). Confirmatory factor analysis indicated that most of the ISEL items
      loaded strongly (>0.45) on the original 4 factors. Mean ISEL score was 68.1,
      which indicated lower social support than population norms. ISEL scores were
      significantly but modestly negatively correlated with grief severity. ISEL total
      scores also varied by sociodemographic and clinical variables; never being
      married, depression or anxiety diagnosis, and living alone were all associated
      with lower ISEL scores. LIMITATIONS: A clinical help-seeking sample, with low
      sociodemographic and geographic variability, may limit the generalizability of
      the findings. Also, analyses were cross-sectional and directionality of
      associations could not be determined. CONCLUSIONS: The 40-item ISEL may be a
      useful measure for those studying social support in the context of CG. Given the
      strikingly low levels of social support, intervention strategies for CG should
      include components addressing social support.

PMID- 28501737
TI  - The BCR/ABL tyrosine kinase inhibitor, nilotinib, stimulates expression of IL
      1beta in vascular endothelium in association with downregulation of miR-3p.
AB  - BCR/ABL tyrosine kinase inhibitors (TKIs) have significantly improved the
      prognosis for in dividuals with chronic myeloid leukemia (CML). However, many
      patients treated with TKIs suffer from TKI-related complications. In particular,
      vascular events such as peripheral artery occlusive disease have become aserious
      clinical problem for patients who receive the TKI, nilotinib. At present, the
      molecular mechanisms by which TKIs cause vascular endothelial cell insults remain
      unknown.This study explored the effects of the TKIs, imatinib, nilotinib and
      dasatinib, on vascular endothelial cells in vitro, and found that only nilotinib
      induced expression of interleukin-1beta (IL-1beta) by vascular endothelial cells.
      Nilotinib-induced IL-1beta expression stimulated the adhesion of monocytes to
      vascular endothelial cells in association with an increase in levels of adhesion
      molecules. MicroRNA database searching identified miR-3121-3p binding sites in
      the 3'-UTR of the IL-1beta gene. Exposure of endothelial cells to nilotinib
      caused downregulation of miR-3121-3p in these cells. Importantly, forced
      expression of miR-3121-3p counteracted nilotinib-induced expression of IL-1beta.
      Importantly, serum levels if IL-1beta were significantly elevated in CML patients
      receiving nilotinib (n=14) compared to those receiving other TKIs (n=16) (3.76+/
      1.22pg/ml vs 0.27+/-0.77pg/ml, p<0.05). Taken together, our data suggest that
      nilotinib decreases levels of miR-3121-3p resulting in an increase in expression
      of IL-1beta and adhesion molecules in vascular endothelial cells. The miR-3121
      3p/IL-1beta axis could be a potential target to prevent vascular events in CML
      patients with high risk of vascular events.

PMID- 28501740
TI  - Prefrontal and amygdala engagement during emotional reactivity and regulation in
      generalized anxiety disorder.
AB  - BACKGROUND: Emotion dysregulation is prominent in generalized anxiety disorder
      (GAD), characterized clinically by exaggerated reactivity to negative stimuli and
      difficulty in down-regulating this response. Although limited research implicates
      frontolimbic disturbances in GAD, whether neural aberrations occur during
      emotional reactivity, regulation, or both is not well understood. METHODS: During
      functional magnetic resonance imaging (fMRI), 30 individuals with GAD and 30
      healthy controls (HC) completed a well-validated explicit emotion regulation task
      designed to measure emotional reactivity and regulation of reactivity. During the
      task, participants viewed negative images ('Look-Negative' condition) and, on
      some trials, used a cognitive strategy to reduce negative affective response
      ('Reappraise' condition). RESULTS: Results from an Analysis of Variance corrected
      for whole brain multiple comparisons showed a significant group x condition
      interaction in the left amygdala and left inferior frontal gyrus (IFG). Results
      from post-hoc analyses showed that the GAD group engaged these regions to a
      greater extent than HCs during Look-Negative but not Reappraise. Behaviorally,
      the GAD group reported feeling more negative than the HC group in each condition,
      although both groups reported reduced negative affect following regulation.
      LIMITATIONS: As comorbidity was permitted, the presence of concurrent disorders,
      like other anxiety disorders and depression, detracts our ability to classify
      neural engagement particular to GAD alone. CONCLUSIONS: Individuals with GAD
      exhibited over-engagement of amygdala and frontal regions during the viewing of
      negative images, compared to HCs. Together, these aberrations may indicate that
      deficits in emotional reactivity rather than regulation contribute to emotion
      dysregulation in those with GAD.

PMID- 28501739
TI  - Risk of postpartum episodes in women with bipolar disorder after lamotrigine or
      lithium use during pregnancy: A population-based cohort study.
AB  - BACKGROUND: Women with bipolar disorder are at high risk for relapse/recurrence
      postpartum. Among all mood stabilizers, lithium has the largest evidence base for
      efficacy in the peripartum period, but lamotrigine is increasingly prescribed for
      bipolar spectrum disorders during pregnancy. The aim of this study was to
      investigate whether lamotrigine use during pregnancy is as effective as lithium
      in the prevention of severe episodes postpartum. METHODS: Danish national
      registries were used to identify pregnancies of women with a diagnosis of bipolar
      spectrum disorders at the time of conception who used lamotrigine or lithium
      during pregnancy. We compared the risk of inpatient psychiatric admission within
      three months postpartum between women who used lamotrigine (N=55) versus lithium
      (N=59) during pregnancy. A logistic regression model was used to calculate crude
      and adjusted odds ratios. RESULTS: We did not find a significant difference in
      the risk of postpartum psychiatric admission between women who used lamotrigine
      versus lithium during pregnancy (7.3% versus 15.3% respectively, adjusted OR
      0.83; 95% CI 0.22-3.14). We adjusted for year of delivery, parity, previous
      admissions and antidepressant/benzodiazepine use during pregnancy. Other
      variables did not differ substantially between groups. LIMITATIONS: We used an
      observational design and therefore patients were not randomized to lamotrigine or
      lithium. The study has a small sample size. CONCLUSIONS: Lamotrigine was not
      inferior to lithium in the prevention of severe postpartum episodes. Our findings
      suggest lamotrigine could be a reasonable alternative treatment option for
      bipolar disorder during pregnancy in patients with vulnerability for depression
      and may prevent severe episodes postpartum.

PMID- 28501741
TI  - Executive functioning deficits among adults with Bipolar Disorder (types I and
      II): A systematic review and meta-analysis.
AB  - BACKGROUND: Executive functioning (EF) deficits contribute to a significant
      proportion of the burden of disease associated with bipolar disorder (BD). Yet,
      there is still debate in the literature regarding the exact profile of executive
      functioning in BD. The purpose of the present project was to assess whether EF
      deficits exist among adults suffering BD, and whether these deficits (if
      apparent) differ by BD subtype. METHODS: A systematic search identified relevant
      literature. Randomised controlled trials that used neuropsychological assessment
      to investigate EF among adults 16-65 years) with a remitted DSM diagnosis of BD
      (type I or II) were included. Studies were published between 1994 and 2015. A
      systematic review and meta-analysis were undertaken. For individual studies,
      standardised mean differences (Cohen's d) and 95% confidence intervals were
      calculated and represented in forest plots to illustrate differences in executive
      performance between groups. Summary effects were produced and tests of
      heterogeneity employed to assess the dispersion and generalisability of results.
      RESULTS: Thirty-six studies met criteria for inclusion. Six domains of EF were
      identified: Set-shifting (SS), inhibition (INH), planning (PLA), verbal fluency
      (VF), working memory (WM), and attention (ATT). BD1s performed worse than HCs in
      all domains. BD2s demonstrated impairment in VF, WM, SS, and ATT. The results
      were mixed for comparisons between BD1s and BD2s, but revealed that BD2s can
      experience similar (or sometimes greater) EF impairment. LIMITATIONS: Only a
      limited number of studies that included BD2 samples were available for inclusion
      in the current study. Subgroup analysis to elucidate potential moderators of
      within-study variance was not undertaken. CONCLUSION: This is the first
      systematic review and meta-analysis to have compared the EF of remitted BD1s,
      BD2s, and HCs. The results provided useful insight into the EF profile of
      patients with BD, and offered commentary as to some of the contradictory results
      reported in the literature. A standardised methodological protocol for assessment
      of EF in BD was proposed. The information in this review could enhance our
      understanding of EF impairment inherent in BD, and the methods and efficacy with
      which clinicians assess and treat this population.

PMID- 28501742
TI  - Differences in the imaging features and distribution of non-indolent and indolent
      mastocytosis: a single institution experience of 29 patients.
AB  - PURPOSE: Compare imaging features of indolent and non-indolent mastocytosis.
      METHODS: For 29 patients, imaging features, imaging indications, and distribution
      of indolent and non-indolent mastocytosis subtypes were analyzed. RESULTS: 16/29
      (55%) patients had three distinct patterns of osseous abnormality, not
      significantly differing between cohorts. Non-indolent disease was more likely to
      present with hepatomegaly (p=0.0004), splenomegaly (p=0.0097), and
      lymphadenopathy (p=0.0079). CT, was the most common initial imaging modality,
      ordered to stage disease in 20 of 29 patients (69%). CONCLUSION: Understanding
      patterns of involvement of indolent and nonindolent mastocytosis across
      modalities could assist radiologists in evaluating mastocytosis.

PMID- 28501743
TI  - Antarctic fish versus human cytoglobins - The same but yet so different.
AB  - The cytoglobins of the Antarctic fish Chaenocephalus aceratus and Dissostichus
      mawsoni have many features in common with human cytoglobin. These cytoglobins are
      heme proteins in which the ferric and ferrous forms have a characteristic
      hexacoordination of the heme iron, i.e. axial ligation of two endogenous
      histidine residues, as confirmed by electron paramagnetic resonance, resonance
      Raman and optical absorption spectroscopy. The combined spectroscopic analysis
      revealed only small variations in the heme-pocket structure, in line with the
      small variations observed for the redox potential. Nevertheless, some striking
      differences were also discovered. Resonance Raman spectroscopy showed that the
      stabilization of an exogenous heme ligand, such as CO, occurs differently in
      human cytoglobin in comparison with Antarctic fish cytoglobins. Furthermore,
      while it has been extensively reported that human cytoglobin is essentially
      monomeric and can form an intramolecular disulfide bridge that can influence the
      ligand binding kinetics, 3D modeling of the Antarctic fish cytoglobins indicates
      that the cysteine residues are too far apart to form such an intramolecular
      bridge. Moreover, gel filtration and mass spectrometry reveal the occurrence of
      non-covalent multimers (up to pentamers) in the Antarctic fish cytoglobins that
      are formed at low concentrations. Stabilization of these oligomers by disulfide
      bridge formation is possible, but not essential. If intermolecular disulfide
      bridges are formed, they influence the heme-pocket structure, as is shown by EPR
      measurements.

PMID- 28501744
TI  - Strategy for improved NH2 detection in combustion environments using an
      Alexandrite laser.
AB  - A new scheme for NH2 detection by means of laser-induced fluorescence (LIF) with
      excitation around wavelength 385nm, accessible using the second harmonic of a
      solid-state Alexandrite laser, is presented. Detection of NH2 was confirmed by
      identification of corresponding lines in fluorescence excitation spectra measured
      in premixed NH3-air flames and on NH2 radicals generated through NH3 photolysis
      in a nonreactive flow at ambient conditions. Moreover, spectral simulations allow
      for tentative NH2 line identification. Dispersed fluorescence emission spectra
      measured in flames and photolysis experiments showed lines attributed to
      vibrational bands of the NH2 A2A1<-X2B1 transition but also a continuous
      structure, which in flame was observed to be dependent on nitrogen added to the
      fuel, apparently also generated by NH2. A general conclusion was that
      fluorescence interferences need to be carefully considered for NH2 diagnostics in
      this spectral region. Excitation for laser irradiances up to 0.2GW/cm2 did not
      result in NH2 fluorescence saturation and allowed for efficient utilization of
      the available laser power without indication of laser-induced photochemistry.
      Compared with a previously employed excitation/detection scheme for NH2 at around
      630nm, excitation at 385.7nm showed a factor of ~15 higher NH2 signal. The
      improved signal allowed for single-shot NH2 LIF imaging on centimeter scale in
      flame with signal-to-noise ratio of 3 for concentrations around 1000ppm,
      suggesting a detection limit around 700ppm. Thus, the presented approach for NH2
      detection provides enhanced possibilities for characterization of fuel-nitrogen
      combustion chemistry.

PMID- 28501745
TI  - Paper based diagnostics for personalized health care: Emerging technologies and
      commercial aspects.
AB  - Personalized health care (PHC) is being appreciated globally to combat clinical
      complexities underlying various metabolic or infectious disorders including
      diabetes, cardiovascular, communicable diseases etc. Effective diagnoses majorly
      depend on initial identification of the causes which are nowadays being practiced
      in disease-oriented approach, where personal health profile is often overlooked.
      The adoption of PHC has shown significantly improved diagnoses in various
      conditions including emergency, ambulatory, and remote area. PHC includes
      personalized health monitoring (PHM), which is its integral part and may provide
      valuable information's on various clinical conditions. In PHC, bio-fluids are
      analyzed using various diagnostic devices including lab based equipment and
      biosensors. Among all types of biosensing systems, paper based biosensors are
      commercially attracted due to its portability, easy availability, cheaper
      manufacturing cost, and transportability. Not only these, various intrinsic
      properties of paper has facilitated the development of paper based miniaturized
      sensors, which has recently gained ASSURED (Affordable, Sensitive, Specific, User
      friendly, Rapid and Robust, Equipment free, Deliverable to all end-users) status
      for point of care diagnosis in miniaturized settings. In this review, importance
      of paper based biosensors and their compatibility for affordable and low cost
      diagnostics has been elaborated with various examples. Limitations and strategies
      to overcome the challenges of paper biosensor have also been discussed. We have
      provided elaborated tables which describe the types, model specifications,
      sensing mechanisms, target biomarkers, and analytical performance of the paper
      biosensors with their respective applications in real sample matrices. Different
      commercial aspects of paper biosensor have also been explained using SWOT
      (Strength, Weakness, Opportunities, Threats) analysis.

PMID- 28501746
TI  - A label-free nanostructured plasmonic biosensor based on Blu-ray discs with
      integrated microfluidics for sensitive biodetection.
AB  - Nanostructure-based plasmonic biosensors have quickly positioned themselves as
      interesting candidates for the design of portable optical biosensor platforms
      considering the potential benefits they can offer in integration,
      miniaturization, multiplexing, and real-time label-free detection. We have
      developed a simple integrated nanoplasmonic sensor taking advantage of the
      periodic nanostructured array of commercial Blu-ray discs. Sensors with two gold
      film thicknesses (50 and 100nm) were fabricated and optically characterized by
      varying the oblique-angle of the incident light in optical reflectance
      measurements. Contrary to the use normal light incidence previously reported with
      other optical discs, we observed an enhancement in sensitivity and a narrowing of
      the resonant linewidths as the light incidence angle was increased, which could
      be related to the generation of Fano resonant modes. The new sensors achieve a
      figure of merit (FOM) up to 35 RIU-1 and a competitive bulk limit of detection
      (LOD) of 6.3*10-6 RIU. These values significantly improve previously reported
      results obtained with normal light incidence reflectance measurements using
      similar structures. The sensor has been combined with versatile, simple, ease to
      fabricate microfluidics. The integrated chip is only 1cm2 (including a PDMS flow
      cell with a 50um height microfluidic channel fabricated with double-sided
      adhesive tape) and all the optical components are mounted on a 10cm*10cm portable
      prototype, illustrating its facile miniaturization, integration and potential
      portability. Finally, to assess the label-free biosensing capability of the new
      sensor, we have evaluated the presence of specific antibodies against the GTF2b
      protein, a tumor-associate antigen (TAA) related to colorectal cancer. We have
      achieved a LOD in the pM order and have assessed the feasibility of directly
      measuring biological samples such as human serum.

PMID- 28501747
TI  - Equilibrium, kinetic and thermodynamic studies for adsorption of BTEX onto
      Ordered Mesoporous Carbon (OMC).
AB  - Chemical and petrochemical industries produce substantial amounts of wastewater
      everyday. This wastewater contains organic pollutants such as benzene, toluene,
      ethylbenzene and xylenes (BTEX) that are toxic to human and aquatic life. Ordered
      Mesoporous Carbon (OMC), the adsorbent that possesses the characteristics of an
      ideal adsorbent was investigated to understand its properties and suitability for
      BTEX removal. Adsorption isotherms, adsorption kinetics, the effects of initial
      BTEX concentrations and temperatures on the adsorption process were studied. The
      OMCs were characterized using surface area and pore size analyzer, transmission
      electron microscopy (TEM), elemental analysis, thermogravimetric analysis (TGA)
      and fourier transform infrared spectroscopy (FTIR). The results suggested that
      the Langmuir Isotherm and Pseudo-Second-Order Models described the experimental
      data well. The thermodynamic parameters, Gibbs free energy (DeltaG degrees ), the
      enthalpy change (DeltaH degrees ) and the entropy change (DeltaS degrees ) of
      adsorption indicated that the adsorption processes were physical, endothermic,
      and spontaneous. In addition, OMC had 27% higher overall adsorption capacities
      compared to granular activated carbon (GAC).

PMID- 28501748
TI  - Systematic screening and characterization of prototype constituents and
      metabolites of total astragalosides using HPLC-ESI-IT-TOF-MSn after oral
      administration to rats.
AB  - Astragalosides (AGs) are the main bioactive constituents in Astragali Radix (AR),
      and have a wide range of pharmacological properties, including immunoregulatory,
      cardioprotective, neuroprotective, antioxidative, antidiabetic, and
      antinociceptive effects. However, the metabolism of total AGs remains unclear. To
      clarify the metabolic fate of AGs after oral administration to rats, total AGs
      were isolated from AR extracts using AB-8 macroporous resin chromatography and
      preparative HPLC, and then analyzed using HPLC-DAD-ELSD and LC-MS. HPLC-ESI-IT
      TOF-MSn was used to systematically screen and characterize prototype constituents
      and metabolites of total AGs in rat feces, urine, and plasma samples. As a
      result, 123 AG-related compounds from feces were detected and structurally
      characterized. Among the 123 compounds, 107 were phase I metabolites, of which 91
      were new metabolites, and 73 were new compounds. In addition, six prototype
      constituents in urine, and one in plasma were detected. The main metabolic sites
      in the structure of cycloastragenol (CAG), the aglycone of AGs, were found to be
      the 9, 19-cyclopropane ring (E ring) and the 20, 24-furan ring (F ring). The
      cleavage mode of CAG derivatives in negative ion mode was identified, and was
      found to be highly dependent on the integrity of the E ring. Mono- to tetra
      hydroxylated and carboxyl substituted metabolites were tentatively identified.
      Deglycosylation, hydroxylation, dehydrogenation, isomerization, ring cleavage,
      and carboxyl substitution were considered to be the major metabolic reactions
      involved in the formation of the metabolites, among which carboxyl substitution
      was a novel metabolic reaction. In summary, after total AGs were orally
      administered to rats, their constituents were extensively metabolized in a phase
      I manner, and the metabolites were excreted mainly into feces. To our knowledge,
      this is the first systematic study on the metabolism of total AGs. The results
      give us insight into the metabolic profiles of total AGs in vivo, and provide a
      foundation for identifying effective forms of AGs and exploring their mechanism
      in future studies.

PMID- 28501749
TI  - Characterization of flavonol mono-, di-, tri- and tetra-O-glycosides by ultra
      performance liquid chromatography-electrospray ionization-quadrupole time-of
      flight mass spectrometry and its application for identification of flavonol
      glycosides in Viola tianschanica.
AB  - In this study, 21 flavonol O-glycoside standards including flavonol mono-, di-,
      tri- and tetra-O-glycosides have been systematically studied by ultra-high
      performance liquid chromatography-electrospray ionization-quadrupole time-of
      flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) in the negative ionization mode to
      analyze their fragmentation patterns. Here for the first time, the Z23- fragment
      (corresponding to the loss of C-2" terminal sugar moiety) was observed in MS/MS
      spectra of flavonol 3-O-triglycosides. The intensity ratio of [Y0-H]-/Y0- was
      proposed as a criterion to distinguish the interglycosidic 1->2 and 1->6 linkages
      in flavonol 3-O-diglycosyl-7-O-monoglycosides. The established fragmentation
      behaviors have been successfully applied to characterization of flavonol
      glycosides in Viola tianschanica. A total of 30 flavonoid glycosides including 3
      flavonol mono-O-glycosides, 10 di-O-glycosides, 10 tri-O-glycosides, 4 tetra-O
      glycosides and 3 flavone di-C-glycosides were identified or tentatively
      identified on the base of their UV profiles, MS/MS data and/or by comparing with
      reference substances. Among these 15 flavonoid glycosides were reported from V.
      tianschanica for the first time.

PMID- 28501750
TI  - Development, validation and application of a novel liquid chromatography tandem
      mass spectrometry assay measuring uracil, 5,6-dihydrouracil, 5-fluorouracil, 5,6
      dihydro-5-fluorouracil, alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro
      beta-alanine in human plasma.
AB  - The plasma 5,6-dihydrouracil/uracil (UH2/U) ratio is a possible phenotypic marker
      of dihydropyrimidine dehydrogenase (DPD) activity, hence an index of 5
      fluorouracil (5-FU) response and toxicity. Studies have re-affirmed the value of
      5-FU and 5,6-dihydro-5-fluorouracil (FUH2) for therapeutic drug monitoring (TDM).
      However, FUH2 has limited stability in plasma, necessitating expedited plasma
      separation and freezing, where routine compliance may not be easy. The
      metabolites alpha-fluoro-beta-ureidopropionic acid (FUPA) and alpha-fluoro-beta
      alanine (FbetaAL) are stable in plasma and are probable candidates for TDM. This
      paper describes development, validation and application of an LC-MS/MS assay
      quantifying U, UH2, 5-FU, FUH2, FUPA and FbetaAL in human plasma. Extraction was
      by salt-assisted liquid-liquid extraction (LLE) in two-stages with pH adjustment.
      The supernatants were mixed, dried and reconstituted. Analytes were resolved on
      the Luna PFP (2) (150*2.00mm, 3MU) column by gradient elution and analyzed by
      tandem mass spectrometry via electrospray ionisation in positive polarity. The
      analytical response was linear (r2>=0.99) in the concentration (ng/mL) ranges: 50
      10 000 for FbetaAL and FUH2, 50-5 000 for FUPA, 50-100 000 for 5-FU, 5-200 for U
      and 10-400 for UH2. Within- and between-run accuracy and precision were <= 10.2%
      and <= 9.8% respectively across the QC range and inclusive of LLOQ. The internal
      standard (IS) normalised matrix effects were within 93-112% with CV of <= 9.7%
      and normalised recoveries were within 91-107% with CV of <= 9.8%. This robust
      assay was successfully applied to samples from rectal and colorectal cancer
      patients (n=10) on 5-FU. Deviations <= 2.0% from the mean values were observed
      when incurred samples were reanalysed.

PMID- 28501751
TI  - The state of everyday quantitative EEG use in Canada: A national technologist
      survey.
AB  - PURPOSE: This study sought to determine the state of quantitative EEG (QEEG) use
      in Canada, as QEEG may provide a partial solution to the issue of escalating EEG
      demand against insufficient health care resources. METHODS: A 10-item survey
      questionnaire was administered to participants at the annual meeting of the
      Canadian Association of Electroneurophysiology Technologists, which was held in
      parallel with the annual meeting of the Canadian Neurological Sciences
      Federation. RESULTS: At least 70% of the Canadian population has QEEG access
      through academic medical institutions with applicability to adults and children.
      QEEG was clinically used 50% in real-time and 50% retrospectively in the critical
      care and epilepsy monitoring units for long-term monitoring and automated seizure
      detection. QEEG trend use, montage use, and duration were variable. CONCLUSION:
      To cope with insufficient health care resources, QEEG is in surprisingly frequent
      clinical use across Canada. There is no consensus on optimal QEEG trends and
      montages. The relative ubiquity of QEEG affords an excellent opportunity for
      research as increasing EEG demand outpaces dwindling health care resources into
      the foreseeable future.

PMID- 28501752
TI  - Effects of dust, formaldehyde and delayed feeding on early postnatal development
      of broiler chickens.
AB  - We investigated effects of perinatal exposure to dust or formaldehyde and the
      moment of first feed intake after hatching on broiler chicken development during
      the first week of life. Four environmental treatments were used from 468 until
      512h of incubation: control (CONT), heat treated dust (HTD), untreated dust (UTD)
      or formaldehyde disinfection (FORM). After hatching, all chickens were assigned
      to 1 of 2 feeding treatments: early feeding (EF; feed and water available in the
      hatcher) or delayed feeding (DF). After 512h of incubation (day 0), chickens were
      reared until day 7 of age. In DF chickens, body weight (BW), yolk free body mass
      (YFBM) and relative liver weight did not differ among environmental treatments at
      day 0. However, in EF chickens BW at day 0 was greater in HTD chickens than in
      UTD and FORM chickens. YFBM in EF chickens at day 0 was greater when chickens
      were exposed to HTD compared to the other environmental treatments. In EF
      chickens, relative liver weight was greater in HTD chickens than in FORM. In DF
      chickens, BW at day 0 was positively related with hatching time (HT). In EF
      chickens, YFBM was positively related to HT. Residual yolk weight at day 0 was
      positively related with HT, whereas relative liver weight and microbicidal
      capacity were negatively related with HT. This study demonstrated that
      formaldehyde and dust during the hatching phase affect broiler chicken
      development at pulling from the incubator, but not at day 7.

PMID- 28501753
TI  - Relevance of cutoff on a 4th generation ELISA performance in the false positive
      rate during HIV diagnostic in a low HIV prevalence setting.
AB  - BACKGROUND: Despite the high specificity of fourth-generation enzyme immunoassays
      (4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value
      is low in populations with low HIV prevalence. Thus, screening should be
      optimized to reduce false positive results. OBJECTIVES: The influence of sample
      cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the
      routine HIV diagnosis in a low HIV prevalence population was evaluated. STUDY
      DESIGN: A total of 30,201 sera were tested for HIV diagnosis using Abbott
      Architect(r) HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months.
      Architect S/CO values were recorded, comparing the HIV-1 positive results
      following Architect interpretation (S/CO>=1) with the final HIV-1 diagnosis by
      confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC
      curve was also performed. RESULTS: Among the 30,201 HIV performed tests, 256
      (0.85%) were positive according to Architect interpretation (S/CO>=1) but only
      229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27
      (10.5%) of 256 samples with S/CO>=1 by Architect were false positive diagnose.
      The false positive rate decreased when the S/CO ratio increased. All 19 samples
      with S/CO <=10 were false positives and all 220 with S/CO>50 true HIV-positives.
      The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative
      results were found. CONCLUSIONS: We show that very low S/CO values during HIV-1
      screening using Architect can result HIV negative after confirmation by LIA and
      NAT. The false positive rate is reduced when S/CO increases.

PMID- 28501754
TI  - Expectant futures and an early diagnosis of Alzheimer's disease: Knowing and its
      consequences.
AB  - Efforts to diagnose Alzheimer's disease (AD) at earlier stages as a means to
      managing the risks of an ageing population, dominate scientific research and
      healthcare policy in the UK. It is anticipated that early diagnosis will maximise
      treatment options and enable patients to 'prepare for their future' in terms of
      care. Drawing on qualitative data gathered across an out-patient memory service
      and in-patient hospital in the UK, the purpose of this paper is to examine the
      ways in which the hopeful promissory claims of early diagnosis as it maintains
      the dominant biomedical model for managing AD, are negotiated by healthcare
      practitioners. Developing the analytical standpoint of the sociology of
      expectations, this paper demonstrates that early diagnosis has the potential to
      'close off' hopeful promissory visions of the future in two ways. Firstly, it
      (re)produces the fearful anticipations of AD built around expectations concerning
      the ageing future 'self', and secondly it produces uncertainty in terms of the
      availability of care as material resource. Whilst practitioners account for the
      uncertainties and anxieties it produces for patients and their families, they
      also convey a sense of ambivalence concerning early diagnosis. This article
      captures the internal conflicts and contradictions inherent to practitioners'
      perspectives regarding the repercussions of early diagnosis and concludes by
      arguing that it effaces the uncertainties and anxieties that it produces in
      practice as it restricts the co-existence of narratives for making sense of
      memory loss beyond 'loss of self', and fails to recognise care as a viable
      alternative for managing AD.

PMID- 28501755
TI  - New challenges for verbal autopsy: Considering the ethical and social
      implications of verbal autopsy methods in routine health information systems.
AB  - Verbal autopsy (VA) methods are designed to collect cause-of-death information
      from populations where many deaths occur outside of health facilities and where
      death certification is weak or absent. A VA consists of an interview with a
      relative or carer of a recently deceased individual in order to gather
      information on the signs and symptoms the decedent presented with prior to death.
      These details are then used to determine and assign a likely cause-of-death. At a
      population level this information can be invaluable to help guide prioritisation
      and direct health policy and services. To date VAs have largely been restricted
      to research contexts but many countries are now venturing to incorporate VA
      methods into routine civil registration and vital statistics (CRVS) systems.
      Given the sensitive nature of death, however, there are a number of ethical,
      legal and social issues that should be considered when scaling-up VAs,
      particularly in the cross-cultural and socio-economically disadvantaged
      environments in which they are typically applied. Considering each step of the VA
      process this paper provides a narrative review of the social context of VA
      methods. Harnessing the experiences of applying and rolling out VAs as part of
      routine CRVS systems in a number of low and middle income countries, we identify
      potential issues that countries and implementing institutions need to consider
      when incorporating VAs into CRVS systems and point to areas that could benefit
      from further research and deliberation.

PMID- 28501756
TI  - Dangertalk: Voices of abortion providers.
AB  - Researchers have described the difficulties of doing abortion work, including the
      psychosocial costs to individual providers. Some have discussed the self
      censorship in which providers engage in to protect themselves and the pro-choice
      movement. However, few have examined the costs of this self-censorship to public
      discourse and social movements in the US. Using qualitative data collected during
      abortion providers' discussions of their work, we explore the tensions between
      their narratives and pro-choice discourse, and examine the types of stories that
      are routinely silenced - narratives we name "dangertalk". Using these data, we
      theorize about the ways in which giving voice to these tensions might transform
      current abortion discourse by disrupting false dichotomies and better reflecting
      the complex realities of abortion. We present a conceptual model for dangertalk
      in abortion discourse, connecting it to functions of dangertalk in social
      movements more broadly.

PMID- 28501757
TI  - Subjective social status and premedical students' attitudes towards medical
      school.
AB  - Although students from lower socioeconomic backgrounds are more likely to depart
      from the medical education pipeline, little is known about how premedical
      students' social origins influence the adversities they face, the resources they
      possess, or the internal struggles they confront in deciding whether or not to
      pursue a career in medicine. Using original data collected from premedical
      students at a flagship state university in the Midwest (N = 364), this study
      explores how subjective social status shapes students' reservations about medical
      school attendance and their perceptions of external pressure to pursue a career
      in medicine. Status-based discrepancies in financial strains, social capital, and
      interpersonal stressors-and the degree to which variation across these measures
      mediates status differences in medical school outlook-are also explored. Net of
      objective measures of social class, results suggest that doubts about attending
      medical school and feeling that not attending medical school will let down one's
      community are more prevalent among premeds who identify as lower status. These
      group differences are explained-at least in part-by lower status premedical
      students' perceptions of financial hardships, more limited reserves of social
      capital, and more frequent encounters with class-based discrimination and with
      educators who discourage their career aspirations.

PMID- 28501758
TI  - Modulating anosognosia for hemiplegia: The role of dangerous actions in emergent
      awareness.
AB  - Anosognosia for hemiplegia is a lack of awareness of motor deficits following a
      right hemisphere lesion. Residual forms of awareness co-occur with an explicit
      denial of hemiplegia. The term emergent awareness refers to a condition in which
      awareness of motor deficits is reported verbally during the actual performance of
      an action involving the affected body part. In this study, two tasks were used to
      explore the potential effects of i) attempting actions which are impossible for
      sufferers of hemiplegia and ii) attempting actions which are potentially
      dangerous. Sixteen hemiplegic patients (8 anosognosic, and 8 non-anosognosic)
      were asked to perform both potentially dangerous and neutral actions. Our results
      confirm an increase in emergent awareness in anosognosic patients during the
      execution of both of these types of action. Moreover, actions that are
      potentially dangerous improved the degree of awareness. However, lesions in the
      fronto-temporal areas appear to be associated with a reduced effect of action
      execution (emergent awareness) while lesions in the basal ganglia and amygdale
      and the white matter underlying the insula and fronto-temporal areas are
      associated with a lesser degree of improvement resulting from attempting to
      perform dangerous actions.

PMID- 28501759
TI  - Resource utilization for non-operative cervical radiculopathy: Management by
      surgeons versus non-surgeons.
AB  - OBJECTIVES: To compare the estimated resource utilization for non-operative
      treatment of cervical radiculopathy if managed by surgeons versus non-surgeons.
      PATIENTS AND METHODS: A Cervical Spine Research Society-sponsored survey was
      administered at a national spine surgery conference to surgeons and non-surgeons,
      as classified above. The survey asked questions regarding resource utilization
      and perceived costs for the "average patient" with cervical radiculopathy managed
      non-operatively. Resource utilization and perceived costs were compared between
      surgeon and non-surgeon participants, and between private practice and academic
      and/or hybrid groups that combine academic and private practices. RESULTS: In
      total, 101 of the 125 conference attendees participated in the survey (return
      rate 80.8%, of which 60% were surgeons). Surgeon and non-surgeon estimates for
      duration of non-operative care did not differ (3.3 versus 4.2 months, p=0.071).
      Estimates also did not differ for estimated number of physical therapy visits
      (10.5 versus 10.5, p=0.983), cervical injections (1.4 versus 1.7, p=0.272),
      chiropractic visits (3.1 versus 3.7, p=0.583), or perceived days off from work
      (14.9 versus 16.3, p=0.816). The only difference identified was that surgeon
      estimates of the number of physician visits while providing non-operative care
      were lower than non-surgeon estimates (3.2 versus 4.0, p=0.018). In terms of
      estimated costs, surgeon and non-surgeon were mostly similar (only difference
      being that surgeon estimates for the total cost of physician visits per patient
      were lower than non-surgeon estimates ($382 versus $579, p=0.007). Surgeon
      estimates for the percent of their patients that go on to receive surgery within
      6 months were higher than non-surgeon estimates (28.6% versus 18.8%, p=0.018).
      Similarly, surgeon estimates for the percent of their patients to go on to
      receive surgery within 2 years were higher than non-surgeon estimates (37.8%
      versus 24.8%, p=0.013). Academic/hybrid and private practice group resource
      utilization estimates and costs were also compared, and no significant
      differences were found in any comparisons. Additionally, no significant
      differences were found in these groups for duration of non-operative care, or the
      estimates of the percent of patients who go on to receive surgery within 6 months
      or two years. CONCLUSION: These data suggest that patients with cervical
      radiculopathy managed by surgeons and those by non-surgeons have overall similar
      resource utilization during a non-operative trial. This suggests that relatively
      similar care is provided regardless of whom initiates the non-operative trial
      (surgeon or non-surgeon). Although surgeons thought their patients more likely to
      undergo surgery following a non-operative trial, this may be a bias due to
      patient referral-specifically, surgeons may be more likely than non-surgeons to
      manage patients with more severe or longer-standing radiculopathy.

PMID- 28501761
TI  - Improving the quality of the intensive care follow-up of ventilated patients
      during a national registration program.
AB  - OBJECTIVES: The Belgian Public Health Organization is concerned with rates of
      hospital-acquired infections like ventilator-associated pneumonia (VAP).
      Implementing best practice guidelines for these nosocomial infections has
      variable success in the literature. This retrospective study was undertaken to
      see whether implementation of the evidence-based practices as a bundle was
      feasible, would influence compliance, and could reduce the rates of VAP. STUDY
      DESIGN: We utilized easily collectable data about regular care to rapidly assess
      whether interventions already in place were effectively successfully applied.
      This avoided cumbersome data collection and review. METHODS: Retrospective
      compliance rates and VAP ratios were compared using z tests with P-values < 0.05
      considered statistically significant. This data review attempted to examine the
      impact of education campaigns, staff meetings, in-services, physician checklist,
      nurse checklist, charge nurse checklist implementation, systematic VAP bundle
      application, and systematic protocols for oral care and sedation protocols.
      Additionally, VAP ratio could be registered by the participating centers.
      RESULTS: A total of 10,211 intensive care unit (ICU) patients were included in
      the study which represents 66,817 ICU days under artificial ventilation with an
      endotracheal tube. The general compliance for VAP bundle raised from VAP was 61%
      in February 2012 and 74.16% in December 2012 (P < 0.001). The incidence rate of
      VAP went from 8.34 occurrences/1000 vent days in 2009 to 4.78 occurrences/1000
      vent days in 2012 (P < 0.001-Pearson test). CONCLUSIONS: Efforts to improve
      physician and staff education, and checklist implementation resulted in an
      increase in compliance for VAP bundle and a decrease in VAP ratio. This study
      confirms the applicability of best practice guidelines about regular care but
      results on VAP incidence have to be confirmed.

PMID- 28501760
TI  - Stromal PDGFR-alpha Activation Enhances Matrix Stiffness, Impedes Mammary Ductal
      Development, and Accelerates Tumor Growth.
AB  - The extracellular matrix (ECM) is critical for mammary ductal development and
      differentiation, but how mammary fibroblasts regulate ECM remodeling remains to
      be elucidated. Herein, we used a mouse genetic model to activate platelet derived
      growth factor receptor-alpha (PDGFRalpha) specifically in the stroma.
      Hyperactivation of PDGFRalpha in the mammary stroma severely hindered pubertal
      mammary ductal morphogenesis, but did not interrupt the lobuloalveolar
      differentiation program. Increased stromal PDGFRalpha signaling induced mammary
      fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid
      (HA) and collagen deposition. Mammary fibroblasts with PDGFRalpha hyperactivation
      also decreased hydraulic permeability of a collagen substrate in an in vitro
      microfluidic device assay, which was mitigated by inhibition of either PDGFRalpha
      or HA. Fibrosis seen in this model significantly increased the overall stiffness
      of the mammary gland as measured by atomic force microscopy. Further, mammary
      tumor cells injected orthotopically in the fat pads of mice with stromal
      activation of PDGFRalpha grew larger tumors compared to controls. Taken together,
      our data establish that aberrant stromal PDGFRalpha signaling disrupts ECM
      homeostasis during mammary gland development, resulting in increased mammary
      stiffness and increased potential for tumor growth.

PMID- 28501762
TI  - Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are
      they really heterogeneous? Insights from the FFCD-GTE national cohort.
AB  - BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero
      pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent
      studies suggest prognostic heterogeneity. We designed within the French Group of
      Endocrine Tumours a prospective cohort to gain insight in the prognostic
      stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with
      a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be
      included in this national cohort. Adenoneuroendocrine tumours were excluded.
      RESULTS: 253 patients from 49 centres were included. Median age was 66 years.
      Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach
      (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis
      in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients.
      Among the 147 (58%) cases reviewed by an expert pathological network, 39% were
      classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75%
      (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant
      adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR]
      = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR =
      3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After
      first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152),
      objective response, progression-free survival and overall survival were 50%, 6.2
      and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI
      regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC
      which show the predominance of large cell type and advanced stage at diagnosis.
      Prognosis was found more homogeneous than previously reported, mainly impacted by
      PS and tumour burden.

PMID- 28501763
TI  - Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast
      cancer patients: 6-year results of the prospective randomised multicentre phase
      III UNICANCER-PACS 05 trial (UCBG-0106).
AB  - PURPOSE: Optimal duration of adjuvant chemotherapy in the treatment of early
      stage breast cancer remained to be investigated rigorously for the standard
      regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC)
      and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles
      of FEC 100 present an advantage, or not, compared with only four cycles was
      tested directly in a phase III prospective multicentre trial. PATIENTS AND
      METHODS: Between 2002 and 2006, 1515 women between 18 and 65 degrees years of
      age, with node negative N(-) high-risk early-stage breast cancer, were included
      in the study following breast surgery and axillary lymph node dissection or
      procedure by sentinel node technique. Inclusion in the study required tumour size
      T >= 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen
      receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade
      II or III and age <= 35 degrees years. Patients were randomly assigned to either
      six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an
      absolute difference >=6% in disease-free survival (DFS) at 5 degrees years.
      RESULTS: At 6.1 degrees years median follow-up, with 91 (12%) events recorded in
      Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was
      associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95%
      [0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P
      = .12). CONCLUSION: Differences in chemotherapy duration did not induce notably
      different outcomes in our cohort of high-risk patients. CLINICAL TRIAL REGISTRY
      NUMBER: NCT00055679, Agence National de Securite du Medicament (ANSM) - France.

PMID- 28501764
TI  - Open-label, multicentre safety study of vemurafenib in 3219 patients with
      BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long
      term responders' analysis.
AB  - BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib is an
      effective and tolerable treatment option for patients with metastatic melanoma
      harbouring BRAFV600 mutations. We assessed the safety of vemurafenib in a large
      population of patients with few alternative treatment options; we report updated
      2-year safety. METHODS: This was an open-label, multicentre study of vemurafenib
      (960 mg bid) in patients with previously treated or untreated BRAF mutation
      positive metastatic melanoma (cobas(r) 4800 BRAF V600 Mutation Test). The primary
      end-point was safety; efficacy end-points were secondary. An exploratory analysis
      was performed to assess safety outcomes in patients with long duration of
      response (DOR) (>=12 or >=24 months). RESULTS: After a median follow-up of 32.2
      months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued
      treatment. Adverse events (AEs) were largely consistent with previous reports;
      the most common all-grade treatment-related AEs were arthralgia (37%), alopecia
      (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs
      were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the
      exploratory analysis, patients with DOR >=12 months (n = 287) or >=24 months (n =
      133) were more likely to experience grade 3/4 AEs than the overall population. No
      new specific safety signals were observed with longer vemurafenib exposure.
      CONCLUSIONS: After 2 years' follow-up, safety was maintained in this large group
      of patients with BRAFV600 mutation-positive metastatic melanoma who are more
      representative of routine clinical practice than typical clinical trial
      populations. These data suggest that long-term vemurafenib treatment is effective
      and tolerable without the development of new safety signals.

PMID- 28501765
TI  - Enhanced sublingual immunotherapy by TAT-fused recombinant allergen in a murine
      rhinitis model.
AB  - Allergen-specific sublingual immunotherapy (SLIT) is well known as an effective
      and non-invasive route to induce allergy desensitization. The goal of this study
      was to investigate whether a TAT-fused recombinant allergen could enhance SLIT
      efficacy. BALB/c mice sensitized to the main allergen (Che a 3) of Chenopodium
      album pollen were treated sublingually either with rChe a 3 (100MUg/dose) or rTAT
      Che a 3 (100MUg/dose), two times per week for eight weeks. SLIT with rTAT-Che a 3
      led to significantly greater allergen-specific IgG2a than rChe a 3; however,
      neither rTAT-Che a 3 nor rChe a 3 affected allergen-specific IgE or IgG1 antibody
      levels. In addition, interleukin 4 (IL-4) levels in re-stimulated splenocytes
      from the rTAT-Che a 3 mice were significantly lower than in those from the rChe a
      3 mice, while interferon-gamma (IFN-gamma) was significantly greater in the rChe
      a 3 mice than in the rTAT-Che a 3 mice. Furthermore, sublingual administration of
      rTAT-Che a 3 induced significantly greater TGF-beta secretion in re-stimulated
      splenocytes than administration of rChe a 3. Accordingly, SLIT with rTAT-Che a 3
      led to significantly greater expression of TGF-beta- and Foxp3-specific mRNAs in
      the splenocytes than in those from the rChe a 3 mice. Our findings demonstrate
      that TAT-fused rChe a 3 suppressed the allergic response through preferential
      enhancement of systemic regulatory T-cell (Treg)-mediated immunity responses,
      likely by facilitating allergen capture and presentation by sublingual Langerhans
      like dendritic cells.

PMID- 28501766
TI  - Therapeutic effects of zerumbone in an alkali-burned corneal wound healing model.
AB  - Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal
      alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis,
      leading to vision loss. The purpose of this study was to examine the effects of
      Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was
      induced by alkali-burn injury in BALB/C female mice. Topical ZER (three times per
      day, 3MUl each time, at concentrations of 5, 15, and 30MUM) was applied to treat
      alkali-burned mouse corneas for 14 consecutive days. Histopathologically, ZER
      treatment suppressed alkali burn-induced CNV and decreased corneal epithelial
      defects induced by alkali burns. Corneal tissue treated with ZER showed reduced
      mRNA levels of pro-angiogenic genes, including vascular endothelial growth
      factor, matrix metalloproteinase-2 and 9, and pro-fibrotic factors such as alpha
      smooth muscle actin and transforming growth factor-1 and 2. Immunohistochemical
      analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells
      was significantly decreased in ZER-treated corneas. ZER markedly inhibited the
      mRNA and protein levels of monocyte chemoattractant protein-1 (MCP-1) in human
      corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis
      revealed that ZER decreased the activation of signal transducer and activator of
      transcription 3 (STAT3), with consequent reduction of MCP-1 production by these
      cells. In conclusion, topical administration of ZER accelerated corneal wound
      healing by inhibition of STAT3 and MCP-1 production.

PMID- 28501767
TI  - Garlic-derived organosulfur compound exerts antitumor efficacy via activation of
      MAPK pathway and modulation of cytokines in SGC-7901 tumor-bearing mice.
AB  - Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested
      for its antigastric cancer activities in various preliminary studies. However,
      more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly
      needed. The aim of this study was to investigate the antitumor effects of DATS in
      the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo
      using widely recommended study procedures. DATS suppressed cancer cells
      proliferation and induced cell cycle arrest accompanied by an increase in the
      expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused
      an increase in apoptotic cell death, which involved in accumulations of bax, p53,
      and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK,
      ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen
      activated protein kinase (MAPKs) pathways were involved in DATS-induced
      apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted
      tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS
      inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein
      expressions. In addition, DATS treatment evidently increased the cytokine
      secretions of IL-12, TNF-alpha and IFN-gamma (p<0.05). Biochemical serum analysis
      and histopathological examination indicated no obvious side effects in major
      mouse organs. Therefore, our findings provide a framework for further exploration
      of DATS as a novel chemotherapeutic for human gastric cancer.

PMID- 28501769
TI  - Dietary exposure assessment for arsenic and mercury following submarine tailings
      placement in Ratatotok Sub-district, North Sulawesi, Indonesia.
AB  - The Mesel gold mine in the Ratatotok Sub-district operated between 1996 and 2004
      with tailings disposal via an engineered submarine tailings placement (STP) into
      Buyat Bay. This operation raised concerns of increased levels of arsenic (As) and
      mercury (Hg) associated disease in the local communities from consumption of
      seafood contaminated with anthropogenic As and Hg. This report uses the dietary
      exposure to As and Hg, from local fishermen and market-purchased Codex "as
      consumed" and environmental fish results from the pre-mining baseline (1990
      1995), the mine operational (1996-2004) and post-closure monitoring (2007-2016)
      to examine the potential health effects. The Ratatotok Sub-district consumers
      total As average daily intake from fish was between 152 and 317 MUg/day (adults)
      and 58 and 105 MUg/day (infants). The average daily intake of inorganic arsenic
      (Asi) from the dietary staples fish and rice and drinking water consumption was
      77 MUg/day (adults) and 35 MUg/day (infants) at Buyat Pantai and 39 MUg/day
      (adults) and 19 MUg/day (infants) at Ratatotok township. Fish consumption
      contributed 8.2% (adults) and 6.5% (infants) to total daily Asi intake. Average
      Hg intake from fish consumption, exceeded the FAO WHO PTWI for methylmercury
      (MeHg) for all age and gender groups at Buyat Pantai 4.6 MUg/kg bw/wk (adults)
      and 7.3 MUg/kg bw/wk (infants) and for the infants at Buyat village and Ratatotok
      township (2.5 and 2.8 MUg/kg bw/wk respectively). The Manado City consumers had
      average intakes below the MeHg PTWI. The Hg exceedances resulted from the high
      fish consumption in coastal communities and not elevated levels of Hg in fish. Hg
      exposure levels from the pre-mining baseline, Mesel STP operation and post
      closure monitoring, confirmed that exceedances were unrelated to the tailings
      deposited into Buyat Bay.

PMID- 28501768
TI  - Association between Chinese cooking oil fumes and sleep quality among a middle
      aged Chinese population.
AB  - Poor sleep quality is an important symptom of many medical or psychiatric
      disorders. However, the impact of cooking oil fumes (COFs) on sleep quality has
      not been studied. This population-based cross-sectional study was conducted to
      examine the association between COFs of Chinese household cooking and sleep
      quality. Individual sleep quality assessment was completed in 2197 participants
      with an average age of 37.52 years, through Pittsburgh Sleep Quality Index
      (PSQI). Information about their cooking practice were also collected by self
      reported questionnaire. As an internal biomarker of COFs, urinary 1-hydroxypyrene
      (1-HOP) (n = 562) was further measured using high-performance liquid
      chromatography. Binary logistic regression models were performed to evaluate the
      association between exposure to COFs and individual sleep quality. We found that,
      subjective poor kitchen ventilation, preheating oil to smoking, and cooking for
      over 30 minutes were positively associated with overall poor sleep quality
      (global PSQI score >5) [odds ratio (OR) = 1.75, 95% confidence interval (CI) =
      1.43-2.16; 1.25, (1.03-1.52); 1.42, (1.15-1.76), respectively]. After adjusting
      for potential confounders, subjective poor kitchen ventilation still tend to
      increase the risk of long sleep latency, sleep disturbances, and daytime
      dysfunction [OR = 1.37, 95% CI = 1.09-1.73; 1.91, (1.39-2.61); 1.54, (1.23-1.93),
      respectively]. Similar results were observed in participants who preheated oil to
      smoking [OR = 1.36, 95% CI = 1.08-1.72; 1.55, (1.14-2.14); 1.25, (1.02-1.55),
      respectively] and cooked for over 30 minutes [OR = 1.34, 95% CI = 1.05-1.72;
      1.46, (1.03-2.06); 1.36, (1.08-1.72), respectively]. Furthermore, high urinary 1
      HOP level was also positively associated with overall poor sleep quality (OR =
      2.30, 95% CI = 1.31-4.05). The results indicated that exposure to COFs from
      Chinese household cooking may be a risk factor for poor sleep quality among
      middle-aged Chinese population.

PMID- 28501770
TI  - Effect of limestone, lignite and biochar applied alone and combined on cadmium
      uptake in wheat and rice under rotation in an effluent irrigated field.
AB  - Cadmium (Cd) uptake and accumulation in crop plants, especially in wheat
      (Triticum aestivum) and rice (Oryza sativa) is one of the main concerns for food
      security worldwide. A field experiment was done to investigate the effects of
      limestone, lignite, and biochar on growth, physiology and Cd uptake in wheat and
      rice under rotation irrigated with raw effluents. Initially, each treatment was
      applied alone at 0.1% and combined at 0.05% each and wheat was grown in the field
      and then, after wheat harvesting, rice was grown in the same field without
      additional application of amendments. Results showed that the amendments applied
      increased the grain and straw yields as well as gas exchange attributes compared
      to the control. In both crops, highest Cd concentrations in straw and grains and
      total uptake were observed in control treatments while lowest Cd concentrations
      was observed in limestone + biochar treatment. No Cd concentrations were detected
      in wheat grains with the application of amendments except limestone (0.1%). The
      lowest Cd harvest index was observed in limestone + biochar and lignite + biochar
      treatments for wheat and rice respectively. Application of amendments decreased
      the AB-DTPA extractable Cd in the soil while increasing the Cd immobilization
      index after each crop harvest. The benefit-cost ratio and Cd contents in plants
      revealed that limestone + biochar treatment might be an effective amendment for
      increasing plant growth with lower Cd concentrations.

PMID- 28501771
TI  - Mechanisms of efficient As solubilization in soils and As accumulation by As
      hyperaccumulator Pteris vittata.
AB  - Arsenic (As) in soils is of major environmental concern due to its ubiquity and
      carcinogenicity. Pteris vittata (Chinese brake fern) is the first known As
      hyperaccumulator, which is highly efficient in extracting As from soils and
      translocating it to the fronds, making it possible to be used for
      phytoremediation of As-contaminated soils. In addition, P. vittata has served as
      a model plant to study As metabolisms in plants. Based on the recent advances, we
      reviewed the mechanisms of efficient As solubilization and transformation in
      rhizosphere soils of P. vittata and effective As uptake, translocation and
      detoxification in P. vittata. We also provided future research perspectives to
      further improve As phytoremediation by P. vittata.

PMID- 28501772
TI  - Hyperoside protects against chronic mild stress-induced learning and memory
      deficits.
AB  - Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid
      mainly found in fruits, fruit juices (most notably flavanols, flavanones, and
      anthocyanins) and Chinese traditional medicines. It has been applied to relieve
      pain and improve cardiovascular functions in clinic. However, the effects of
      hyperoside on cognitive impairment induced by chronic stress and the underlying
      molecular mechanisms remain unclear. In the current study, we used chronic mild
      stress (CMS) rats to investigate the effects of hyperoside on learning and memory
      and further explore the possible mechanisms. Our results demonstrated that
      hyperoside reduced the escape latency and the swimming distance of CMS rats in
      Morris water maze test and reversed depressive symptoms in forced swim test (FST)
      and sucrose preference test. In addition, hyperoside increased the expression of
      brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without
      influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a,
      an inhibitor of the BDNF receptor TrkB, prevented the protective effects of
      hyperoside on learning and memory in CMS rats. Taken together, these results
      indicate that hyperoside reverses the cognitive impairment induced by CMS, which
      is associated with the regulation of BDNF signaling pathway.

PMID- 28501774
TI  - Tuning of major signaling networks (TGF-beta, Wnt, Notch and Hedgehog) by miRNAs
      in human stem cells commitment to different lineages: Possible clinical
      application.
AB  - Two distinguishing characteristics of stem cells, their continuous division in
      the undifferentiated state and growth into any cell types, are orchestrated by a
      number of cell signaling pathways. These pathways act as a niche factor in
      controlling variety of stem cells. The core stem cell signaling pathways include
      Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically
      regulate the self-renewal and survival of cancer stem cells. Conversely, stem
      cells' main properties, lineage commitment and stemness, are tightly controlled
      by epigenetic mechanisms such as DNA methylation, histone modifications and non
      coding RNA-mediated regulatory events. MicroRNAs (miRNAs) are cellular switches
      that modulate stem cells outcomes in response to diverse extracellular signals.
      Numerous scientific evidences implicating miRNAs in major signal transduction
      pathways highlight new crosstalks of cellular processes. Aberrant signaling
      pathways and miRNAs levels result in developmental defects and diverse human
      pathologies. This review discusses the crosstalk between the components of main
      signaling networks and the miRNA machinery, which plays a role in the context of
      stem cells development and provides a set of examples to illustrate the extensive
      relevance of potential novel therapeutic targets.

PMID- 28501773
TI  - TRPV4 functions in flow shear stress induced early osteogenic differentiation of
      human bone marrow mesenchymal stem cells.
AB  - Mechanical cues have been shown to induce osteogenic differentiation of bone
      marrow stromal cells (MSCs). The TRPV4 channel, a Ca2+-permeable membrane ion
      channel, is implicated in the transduction of external mechanical stimulation
      into specific intracellular responses in a wide variety of bone cells. However,
      the role of TRPV4 in transducing and regulating the differentiation of human MSCs
      in response to flow shear stress (FSS) is unclear. In this study, using FSS and
      calcium imaging, we demonstrated that FSS activated early osteogenic
      differentiation, as shown by the early osteogenic differentiation marker osterix
      (Osx) and alkaline phosphatase (ALP) staining. Increases in intracellular Ca2+
      and in the percentage of responding cells were induced by FSS. However, the late
      osteogenic differentiation marker Ocn and in vitro mineralization were unchanged
      after FSS stimulation. TRPV4 channels mediated the FSS-induced Ca2+ influx and
      osteogenic differentiation of MSCs, which were inhibited by a selective TRPV4
      blocker HC-067047 and specific Trpv4 siRNA. Ca2+ influx through TRPV4 promoted
      NFATc1 nuclear localization. These results identify an essential role of TRPV4 in
      FSS-induced early osteogenic differentiation of human MSCs.

PMID- 28501775
TI  - Vitamin D: Correlation with biochemical and body composition changes in a
      southern Brazilian population and induction of cytotoxicity in mesenchymal stem
      cells derived from human adipose tissue.
AB  - Studies have shown that metabolic disorders, serum inflammatory markers and
      weight gain (obesity) are correlated with vitamin D deficiency. Therefore, the
      present study correlated the serum calcidiol (s25(OH)D3) levels in a sample of
      individuals from southern Brazil with variables related to metabolic disorders,
      obesity and lifestyle habits and assessed the cytotoxic effect of calcitriol on
      adipose tissue-derived mesenchymal stem cells (ADSCs). The results showed a
      79.23% prevalence of hypovitaminosis D in the study population and a correlation
      (p<0.05) between a low serum vitamin D concentration and an elevated low-density
      lipoprotein cholesterol (LDL-c) level. Univariate linear regression analysis
      using 25(OH)D3 as a regressor showed a negative association (p<0.05) with an
      indoor work environment (beta=-2.305), increased body fat (beta=-0.095), age
      (beta=-0.065) and high-density lipoprotein cholesterol (HDL-c; beta=-0.109). An
      in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      performed with ADSCs using five calcitriol concentrations (15.625, 31.25, 62.5,
      125 and 250nM) indicated cytotoxic potential (p<0.05) at the 62.5nM concentration
      at 48 and 72h and at the 125 and 250nM concentrations at 24, 48 and 72h. The
      results reported herein corroborate one another and suggest a key association
      between vitamin D deficiency and the development of obesity because ADSCs are
      involved in adipose tissue hyperplasia and differentiate into adipocytes that can
      sequester the bioavailable vitamin D necessary for homeostasis.

PMID- 28501776
TI  - Inhibition of SENP3 by URB597 ameliorates neurovascular unit dysfunction in rats
      with chronic cerebral hypoperfusion.
AB  - Disruption of the neurovascular unit (NVU), induced by chronic cerebral
      hypoperfusion (CCH), has been broadly found in various neurological disorders.
      SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and
      microglia, and regulates a variety of cell events. However, whether SENP3 is
      involved in neurovascular injury under the condition of CCH is still elusive. To
      address this issue, we investigated the effect of the fatty acid amide hydrolase
      (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as
      the underling mechanisms. The expression of SENP3 was detected by
      immunochemistry. The function and structure of the NVU was assessed by Western
      blot analysis and transmission electron microscopy. CCH caused the upregulation
      of SENP3, the disruption of cell and non-cell components at the protein level
      within the NVU, and ultrastructural deterioration. The NVU impairment as well as
      overexpression of SENP3 were reversed by treatment with URB597. These results
      reveal a novel neuroprotective role in URB597, which implicates URB597 in the
      amelioration of CCH-induced NVU impairment by inhibiting SENP3.

PMID- 28501777
TI  - MiR-140/BDNF axis regulates normal human astrocyte proliferation and LPS-induced
      IL-6 and TNF-alpha secretion.
AB  - Reactive astrocyte proliferation after spinal cord injury (SCI) contributes to
      glial scar formation that impedes axonal regeneration. The mechanisms underlying
      astrocyte proliferation upon injury remain partially understood. MicroRNAs
      (miRNAs) function as a major class of post-transcriptional gene expression
      regulators that participate in many biological processes. In this study, we
      focused on the functional role of miR-140 in normal human astrocyte (NHA) cell
      proliferation. Ectopic miR-140 expression significantly inhibited NHA cell
      viability and proliferation; miR-140 inhibition exerted the opposite function.
      Commonly, miRNAs exert functions through targeting downstream genes to inhibit
      their expression. In the present study, brain-derived neurotrophic factor (BDNF),
      a regulator of astrocyte proliferation and differentiation, confirmed as a direct
      target of miR-140 in NHA. Through binding to the 3'UTR of BDNF, miR-140 inhibited
      BDNF expression. BDNF overexpression significantly promoted NHA cell viability
      and proliferation; the regulatory effect of miR-140/BDNF on NHA proliferation was
      mediated by PI3K/AKT pathway. Moreover, we evaluated the functional role of miR
      140 in Lipopolysaccharide (LPS)-induced in vitro injury model of astroglial
      cultures; a significantly up-regulated BDNF, interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha expression in response to LPS stimulation was
      observed. After ectopic miR-140 expression, the promotive effect of LPS on BDNF,
      IL-6 and TGF-alpha expression was partially restored. Taken together, miR
      140/BDNF axis regulates NHA proliferation through PI3K/AKT pathway; miR-140 could
      inhibit BDNF, IL-6 and TGF-alpha expression in LPS-induced in vitro injury model.
      MiR-140/BDNF might serve as a promising target in strategy against reactive
      astrocyte proliferation after SCI.

PMID- 28501778
TI  - Upregulation of the long non-coding RNA SNHG1 predicts poor prognosis, promotes
      cell proliferation and invasion, and reduces apoptosis in glioma.
AB  - Long non-coding RNAs (lncRNAs), which are non-coding RNAs with a length above 200
      nucleotides, have emerged as novel and important gene expression modulators in
      carcinogenesis. Recent evidence indicates that the lncRNA small nucleolar RNA
      host gene 1 (SNHG1) functions as an oncogene in several types of human cancers.
      However, its function in the development of glioma remains unknown. The aim of
      this research was to investigate the clinical aspects and biological mechanisms
      of SNHG1 in glioma. SNHG1 expression was measured in glioma tissues and cell
      lines by quantitative real-time PCR (qRT-PCR). The association between SNHG1
      expression in tissues and clinicopathological characteristics and prognosis in
      glioma patients was also explored. Gain-of-function and loss-of-function studies
      using SNHG1 cDNA and siRNA, respectively, were used to investigate the role of
      SNHG1 in cell proliferation, invasion and apoptosis in glioma. SNHG1 was highly
      expressed in glioma tissues, and its upregulation was closely related to old age.
      Kaplan-Meier analysis showed that high expression of SNHG1 was significantly
      associated with poor overall survival (OS). Functionally, ectopic expression of
      SNHG1 enhanced cell proliferation and cell invasion and reduced cell apoptosis in
      vitro, while SNHG1 knockdown reversed these effects. Taken together, our findings
      indicate that SNHG1 functions as an oncogene in glioma and may serve as a novel
      therapeutic target in future treatments.

PMID- 28501779
TI  - Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel
      functions in septic rats.
AB  - BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble
      antioxidant and an essential electron carrier in the mitochondrial respiratory
      chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to
      hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to
      investigate the effects of CoQ10 on survival, mesenteric artery blood flow
      (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal
      ligation and puncture (CLP)-induced sepsis. METHODS: Wistar rats were divided
      into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle
      (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day,
      Sham or CLP operation was performed. 20h after the operations, MABF and
      phenylephrine responses of isolated aortic rings were measured. Tissue samples
      were obtained for histopathological and biochemical evaluations. Furthermore,
      survival rates were monitored throughout 96h. RESULTS: CoQ10 prevented mesenteric
      hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th
      h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP
      induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine
      (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were
      blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney
      malondialdehyde levels and as well as reduced liver and spleen glutathione
      levels. The protective effects of CoQ10 on multiple organ damage were also
      observed histopathologically. CONCLUSIONS: CoQ10 showed protective effects in
      sepsis due to its preservative effects on mesenteric perfusion, aortic function
      and also its anti-inflammatory and antioxidative effects.

PMID- 28501780
TI  - Low power continuous wave-laser seed irradiation effect on Moringa oleifera
      germination, seedling growth and biochemical attributes.
AB  - Recently, laser application in agriculture has gained much attention since plant
      characteristics were improved significantly in response of pre-sowing seed
      treatment. Pre-sowing laser seed treatment effects on germination, seedling
      growth and mineral profile were studied in Moringa olifera. M. olifera healthy
      seeds were exposed to 25, 50, 75mJ low power continuous wave laser light and
      grown under greenhouse conditions. The seedling growth and biochemical attributes
      were evaluated from 10-day-old seedlings. The germination parameters (percentage,
      mean germination time), vigor index, seedling growth (root length, seedling
      length, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight)
      enhanced considerably. The laser energy levels used for seed irradiation showed
      variable effects on germination, seedling growth and mineral profile. The mineral
      contents were recorded to be higher in seedling raised from laser treated seeds,
      which were higher in roots versus shoots and leaves. The effect of laser
      treatment on seedling fat, nitrogen and protein content was insignificant and at
      higher energy level both nitrogen and protein contents decreased versus control.
      Results revealed that M. olifera germination, seedling growth and mineral
      contents were enhanced and optimum laser energy level has more acceleratory
      effect since at three laser energy levels the responses were significantly
      different. Overall the laser energy levels effect on germination and seedling
      growth was found in following order; 75mJ>50mJ>25mJ, where as in case of fat,
      protein and nitrogen contents the trend was as; 25mJ>50mJ and 75mJ. However, this
      technique could possibly be used to improve the M. olifera germination, seedling
      growth, and minerals contents where germination is low due to unfavorable
      conditions.

PMID- 28501781
TI  - Green synthesis of Au-Cu2-xSe heterodimer nanoparticles and their in-vitro
      cytotoxicity, photothermal assay.
AB  - We demonstrate a new route for the synthesis of heterogeneous nanoparticles (NPs)
      composed of a gold domain (Au) and a heavily doped semiconductor domain (Cu2-xSe)
      which exhibit a broad localized surface plasmon resonance (LSPR) arising from
      interactions between two nanocrystal domains. We also demonstrate the in-vitro
      cytotoxicity and photo thermal efficiency of as prepared Au-Cu2-xSe heterodimer
      nanoparticles. This work establishes a new way of tuning LSPR by engineering the
      density of free charge carriers in two interacting domains.

PMID- 28501782
TI  - Combination of the Electro/Fe3+/peroxydisulfate (PDS) process with activated
      sludge culture for the degradation of sulfamethazine.
AB  - In this paper, the major factors affecting the degradation and the mineralization
      of sulfamethazine by Electro/Fe3+/peroxydisulfate (PDS) process (e.g. current
      density, PDS concentration, Fe3+ ions concentration and initial sulfamethazine
      (SMT) concentration) were evaluated. The relevance of this process as a
      pretreatment prior to activated sludge culture was also examined. Regarding the
      impact on SMT degradation and mineralization, the obtained results showed that
      they were significantly enhanced by increasing the current density and the PDS
      concentrations in the ranges 1-40mAcm-2 and from 1 to 10mM respectively; while
      they were negatively impacted by an increase of the initial SMT concentration and
      the Fe3+ concentration, from 0.18 to 0.36mM and from 1 to 4mM respectively. The
      optimal operating conditions were therefore 40mAcm-2 current density, 10mM PDS
      concentrations, 1mM Fe3+, and 0.18mM SMT. Indeed, under these conditions the
      degradation of SMT and its mineralization yield were 100% and 83% within 20min
      and 180min respectively. To ensure a significant residual organic content for
      activated sludge culture after Electro/Fe3+/PDS pre-treatment, the
      biodegradability test and the biological treatment were performed on a solution
      electrolyzed at 40mAcm-2, 10mM PDS concentrations, 1mM Fe3+, and 0.36mM SMT.
      Under these conditions the BOD5/COD ratio increased from 0.07 to 0.41 within 6h
      of electrolysis time. The subsequent biological treatment increased the
      mineralization yield to 86% after 30days, confirming the relevance of the
      proposed combined process.

PMID- 28501783
TI  - Silencing of DNA repair sensitizes pediatric brain tumor cells to gamma
      irradiation using gold nanoparticles.
AB  - We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries
      and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells.
      The delivery vehicle consists of gold NPs coated with a polymeric shell
      comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI).
      NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP
      cells. Further, this reduction in Ape1 expression is associated with an increase
      in DNA damage after irradiation. The results indicate that NP-associated delivery
      of siApe1 is a feasible approach to circumventing pediatric brain tumor
      resistance to radiation therapy.

PMID- 28501784
TI  - Cellular uptake mechanism and clearance kinetics of fluorescence-labeled
      glycyrrhetinic acid and glycyrrhetinic acid-modified liposome in hepatocellular
      carcinoma cells.
AB  - Glycyrrhetinic acid (GA) is a natural pentacyclic triterpene derivative that
      exerts significant effects in the suppression of liver cancer. The receptors of
      GA on liver cells and hepatocellular carcinoma (HCC) cells have drawn broad
      attention. The effects of GA might depend on its transport into and out of cells.
      However, the question has not been previously addressed despite its obvious and
      fundamental importance. In this paper, GA and GA-modified liposome (GA-Lip) were
      labeled with fluorescein isothiocyanate (FITC) or coumarin 6 (Cou6) using
      chemical or pharmaceutical techniques. The transport courses of FITC-GA and GA
      Cou6-Lip were studied in HepG2 cells in vitro. We found that the fluorescence
      labeled GA and GA-Lip uptake and clearance were time-dependent. FITC-GA uptake
      involved passive diffusion and active transport, and the receptors were in the
      cytomembrane proteins. GA-Cou6-Lip uptake was mediated by caveolae-dependent
      endocytosis. In addition, FITC-GA and GA-Cou6-Lip clearance of the HCC cells
      fitted exponential decay and second-order processes, respectively. These findings
      provide new insights into the anti-HCC actions of GA.

PMID- 28501785
TI  - Experimental study of sucralfate intervention for paraquat poisoning in rats.
AB  - OBJECTIVE: This study explored the effects of sucralfate intervention as a novel
      treatment for paraquat (PQ) poisoning in Sprague-Dawley (SD) rats. METHODS: After
      PQ poisoning, the SD rats were randomly divided into the PQ control group
      (treated with normal saline), the sodium bicarbonate (SB) treatment group, and
      the sucralfate (LTL) treatment group. Then, the rats were administered normal
      saline, sodium bicarbonate solution, or sucralfate suspension as an intervention
      by gastric lavage. At 1, 3, 6, and 10days after poisoning, the left lungs of some
      rats were removed to determine the lung wet/dry (W/D) weight ratio. Additionally,
      the serum cytokine levels were measured, and the lung and kidney tissues were
      pathologically examined. RESULTS: After treatment, the signs and symptoms of the
      rats were improved, the mortality rate was reduced, the W/D weight ratio of the
      lung was lower, the cytokine levels [transforming growth factor (TGF)-beta1,
      interleukin (IL)-10, and tumor necrosis factor (TNF)-alpha] were decreased, and
      the pathological injuries of the lungs and kidneys were improved. Moreover,
      sucralfate was significantly more effective than the control (normal saline)
      group and the SB treatment group. CONCLUSION: The results showed that early
      gastrointestinal lavage with sucralfate effectively reduced the inflammatory
      response and lung and kidney injuries and improved the survival of the SD rats.

PMID- 28501786
TI  - QAC modified PVDF membranes: Antibiofouling performance, mechanisms, and effects
      on microbial communities in an MBR treating municipal wastewater.
AB  - Biofouling remains as a critical issue limiting the widespread applications of
      membrane bioreactors (MBRs). The use of antibiofouling membranes is an emerging
      method to tackle this issue. In this study, a polyvinylidene fluoride (PVDF)
      membrane was modified using a quaternary ammonium compound (QAC) to create an
      antibiofouling membrane. The membrane was used in an MBR and the performance,
      mechanisms, and effects on microbial communities of this membrane were compared
      to a control operated in parallel. Results showed that the membrane exhibited a
      significantly reduced transmembrane pressure increase rate of 0.29 kPa/d compared
      with 0.91 kPa/d of the control. Analysis using a confocal laser scanning
      microscope (CLSM) revealed almost complete lack of living microbes on the
      antibiofouling membrane in contrast to the control. However, specific oxygen
      uptake rate and dehydrogenase activity analyses demonstrated no adverse impacts
      on microbial viability of the bulk activated sludge. Bacterial population
      analysis using the Illumina Miseq platform added further evidence that the use of
      antibiofouling membrane did not exert negative influences on richness, diversity
      and structure of the bacterial community. Effluent quality of the test MBR also
      exhibited minimal difference from that of the control reactor. The amount of
      polysaccharides and proteins in the biofouling layer was also significantly
      reduced. Quartz crystal microbalance with dissipation monitoring suggested that
      the antibiofouling membrane only allowed organic matter with strong adhesion
      properties to attach onto the membrane surfaces. These findings highlight the
      potential of the antibiofouling membrane to be used in MBRs for wastewater
      treatment and reclamation.

PMID- 28501787
TI  - Free chlorine and monochloramine inactivation kinetics of Aspergillus and
      Penicillium in drinking water.
AB  - Fungi are near-ubiquitous in potable water distribution systems, but the
      disinfection kinetics of commonly identified fungi are poorly studied. In the
      present study, laboratory scale experiments were conducted to evaluate the
      inactivation kinetics of Aspergillus fumigatus, Aspergillus versicolor, and
      Penicillium purpurogenum by free chlorine and monochloramine. The observed
      inactivation data were then fit to a delayed Chick-Watson model. Based on the
      model parameter estimation, the Ct values (integrated product of disinfectant
      concentration C and contact time t over defined time intervals) for 99.9%
      inactivation of the tested fungal strains ranged from 48.99 mg min/L to 194.7 mg
      min/L for free chlorine and from 90.33 mg min/L to 531.3 mg min/L for
      monochloramine. Fungal isolates from a drinking water system (Aspergillus
      versicolor and Penicillium purpurogenum) were more disinfection resistant than
      Aspergillus fumigatus type and clinical isolates. The required 99.9% inactivation
      Ct values for the tested fungal strains are higher than E. coli, a commonly
      monitored indicator bacteria, and within a similar range for bacteria commonly
      identified within water distribution systems, such as Mycobacterium spp. and
      Legionella spp.

PMID- 28501788
TI  - Dynamic femoral head translations in dysplastic hips.
AB  - BACKGROUND: Developmental dysplasia of the hip is an important disease leading to
      osteoarthritis. Recently, researchers have focused on hip instability as a
      potentially important dynamic factor for osteoarthritis, but the detailed
      kinematics of dysplastic hips during weight-bearing gait have not been reported.
      The purpose of this research is to contrast femoral translation in contralateral
      healthy hips and dysplastic hips during weight-bearing stepping. METHODS: Twelve
      dysplastic hips and eight healthy hips were investigated. Hip joint kinematics
      were analyzed using 3D-2D model-image registration with dynamic fluoroscopic
      images of each hip during a stepping-in-place activity. Femoral translation
      relative to the acetabular center was quantified as instability. FINDINGS: Total
      femoral head translations were significantly different between dysplastic and
      contralateral healthy hips. Mean translation was 1.0mm in dysplastic hips and
      0.4mm in contralateral healthy hips during swing-phase, and consisted of inferior
      translation during early swing phase with a complementary superior translation
      just before foot strike. Total femoral translation was significantly correlated
      to several radiographic indices of hip dysplasia. INTERPRETATION: Superior
      translations of the femur during the end of swing phase may result in altered
      articular contact mechanics, abnormal stresses on the labrum and lost lubricant
      sealing. All of these factors may contribute to joint degeneration and
      osteoarthritis in dysplastic hips.

PMID- 28501789
TI  - Country-specific and individual determinants of dizziness in Europe: results from
      the Survey of Health Ageing and Retirement in Europe (SHARE).
AB  - OBJECTIVES: Dizziness is one of the most common complaints amongst older persons
      and has relevant consequences for functioning. However, the epidemiological
      findings on dizziness are scarce and inconsistent and prevalence varies
      considerably among existing studies. Hence the objective of this study is to
      compare the prevalence of dizziness in persons aged 50 years or older across
      several European countries. The specific aim was to identify country- and person
      specific determinants associated with a higher risk. STUDY DESIGN: Cross
      sectional study. METHODS: Data from the Survey of Health Ageing and Retirement in
      Europe project, covering 20 countries were analysed. Micro-data on more than
      69,000 persons aged 50+ years and additional macro-data on economic inequality,
      climate and urbanisation were included. We applied multilevel models to examine
      the impact of country-50 years or older specific determinants as well as
      individual characteristics on prevalence of dizziness. RESULTS: We found a total
      of 12.4% of the participants in our sample were troubled by dizziness in the last
      6 months. Prevalence ranged from 6.5% to 23.4%. In multilevel analysis several
      determinants on the country (higher proportion of urban population) and on the
      individual level (female gender, living alone, old age, poor education, presence
      of comorbidities, depressive symptoms, sensory problems, lack of physical
      activities) were identified. CONCLUSIONS: In conclusion dizziness is a common
      complaint amongst older Europeans that needs more attention. Further studies
      should investigate the prevalence, determinants and management of defined
      vestibular and non-vestibular causes of dizziness across Europe.

PMID- 28501791
TI  - The jurisprudence of emergency medical care in India: an ethics perspective.
AB  - This paper, which is part of a primary interdisciplinary doctoral research work
      with a qualitative research design, seeks to understand the ethical principles
      that intersect healthcare jurisprudence in litigations where citizens, who have
      encountered death or violations in the provision of critical care, have had to
      take recourse to the courts to get justice.

PMID- 28501792
TI  - Healing ministry and palliative care in Christianity.
AB  - Death is inevitable, but that does not mean it can be planned or imposed. It is
      an ethical imperative that we attend to the unbearable pain and suffering of
      patients with incurable and terminal illnesses. This is where palliative care
      plays a vital role. Palliative care has been growing faster in the world of
      medicine since its emergence as a specialty in the last decade. Palliative care
      helps to reduce physical pain while affirming the aspect of human suffering and
      dying as a normal process. The goal of palliative care is to improve the quality
      of life both of the patient and the family. Palliative care resonates with the
      healing ministry of Christianity that affirms the sanctity and dignity of human
      life from the moment of conception to natural death. Christianity is convinced
      that patients at the very end of their lives, with all their ailments and
      agonies, are still people who have been created in the image and likeness of God.
      The human person is always precious, even when marked by age and sickness. This
      is one of the basic convictions that motivate Christians to take care of the sick
      and the dying. Palliative care is a great opportunity for Christians to manifest
      God's unfailing love for the terminally ill and the dying.

PMID- 28501790
TI  - Obesity aggravates toxic effect of BPA on spermatogenesis.
AB  - Both bisphenol A (BPA) and obesity affect male reproductive system. However,
      whether there is an interaction between them remains poorly understood. The aim
      of the present study was to evaluate the interaction between BPA exposure and
      obesity on semen quality and elucidate the mechanism in humans and animals. We
      firstly analyzed the interaction on semen volume, sperm count per ejaculate,
      sperm concentration and sperm motility in 357 men, and found that urinary BPA
      concentration was significantly correlated with sperm count per ejaculate in
      obese men (beta=-34.62; 95% CI: -60.75, -8.48; P=0.01). Then we validated the
      interaction using lean and obese mice with administration of BPA. Significant
      interactions between BPA exposure and obesity on sperm count and sperm
      concentration was observed in mice. Finally, we conducted metabolomics analyses
      to identify metabolites related to the interaction. Metabolites related to the
      interaction, including capric acid, dodecanoic acid, l-palmitoylcarnitine,
      niacinamide, etc., are known to play critical roles in fatty acid oxidation and
      tricarboxylic acid cycle indicating increased oxidative stress associated with
      male reproductive dysfunction. Thus, our study finds an interaction between BPA
      exposure and obesity on sperm count and reveals potential metabolic mechanisms.
      It emphasizes the importance to study interactions between endocrine disrupting
      chemicals and obesity, and opens avenues for the possible use of animal models in
      identifying the interactions.

PMID- 28501793
TI  - Ethical issues in death, dying and palliation: the IJME Sixth National Bioethics
      Conference.

PMID- 28501794
TI  - Cochrane corner: renal denervation for resistant hypertension-a broken promise?

PMID- 28501795
TI  - Patient preferences for cardiovascular preventive medication: a systematic
      review.
AB  - OBJECTIVE: To systematically review current evidence regarding the minimum
      acceptable risk reduction of a cardiovascular event that patients feel would
      justify daily intake of a preventive medication. METHODS: We used the Web of
      Science to track the forward and backward citations of a set of five key articles
      until 15 November 2016. Studies were eligible if they quantitatively assessed the
      minimum acceptable benefit-in absolute values-of a cardiovascular disease
      preventive medication among a sample of the general population and required
      participants to choose if they would consider taking the medication. RESULTS: Of
      341 studies screened, we included 22, involving a total of 17 751 participants: 6
      studied prolongation of life (POL), 12 studied absolute risk reduction (ARR) and
      14 studied number needed to treat (NNT) as measures of risk reduction
      communicated to the patients. In studies framed using POL, 39%-54% (average: 48%)
      of participants would consider taking a medication if it prolonged life by <8
      months and 56%-73% (average: 64%) if it prolonged life by >=8 months. In studies
      framed using ARR, 42%-72% (average: 54%) of participants would consider taking a
      medication that reduces their 5-year cardiovascular disease (CVD) risk by <3% and
      50%-89% (average: 77%) would consider taking a medication that reduces their 5
      year CVD risk by >=3%. In studies framed using 5-year NNT, 31%-81% (average: 60%)
      of participants would consider taking a medication with an NNT of >30 and 46%-87%
      (average: 71%) with an NNT of <=30. CONCLUSIONS: Many patients require a
      substantial risk reduction before they consider taking a daily medication
      worthwhile, even when the medication is described as being side effect free and
      costless.

PMID- 28501796
TI  - Nitric oxide synthase inhibition restores orthostatic tolerance in young
      vasovagal syncope patients.
AB  - OBJECTIVE: Syncope is sudden transient loss of consciousness and postural tone
      with spontaneous recovery; the most common form is vasovagal syncope (VVS). We
      previously demonstrated impaired post-synaptic adrenergic responsiveness in young
      VVS patients was reversed by blocking nitric oxide synthase (NOS). We
      hypothesised that nitric oxide may account for reduced orthostatic tolerance in
      young recurrent VVS patients. METHODS: We recorded haemodynamics in supine VVS
      and healthy volunteers (aged 15-27 years), challenged with graded lower body
      negative pressure (LBNP) (-15, -30, -45 mm Hg each for 5 min, then -60 mm Hg for
      a maximum of 50 min) with and without NOS inhibitor NG-monomethyl-L-arginine
      acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and
      pressor control for L-NMMA. RESULTS: Controls endured 25.9+/-4.0 min of LBNP
      during Saline+PE compared with 11.6+/-1.4 min for fainters (p<0.001). After L
      NMMA, control subjects endured 24.8+/-3.2 min compared with 22.6+/-1.6 min for
      fainters. Mean arterial pressure decreased more in VVS patients during LBNP with
      Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased
      similarly in controls and VVS patients and was unaffected by L-NMMA. Total
      peripheral resistance increased for controls but decreased for VVS during
      Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular
      resistance increased during LBNP in controls, but decreased in VVS patients
      following Saline+PE which L-NMMA restored. CONCLUSIONS: We conclude that arterial
      vasoconstriction is impaired in young VVS patients, which is corrected by NOS
      inhibition. The data suggest that both pre- and post-synaptic arterial
      vasoconstriction may be affected by nitric oxide.

PMID- 28501797
TI  - Predictors of procedural complications in adult Fontan patients undergoing non
      cardiac procedures.
AB  - OBJECTIVE: Limited data exist regarding the outcomes of non-cardiac procedures
      (NCPs) in adult patients after Fontan operations (Fontan patients). METHODS: To
      compare procedural outcomes after NCPs in Fontan patients with outcomes for two
      matched control groups: patients with repaired congenital heart disease and
      biventricular circulation (CHD-BiV) and patients with no heart disease (NHD). We
      defined cyanosis as oxygen saturation <90% and procedural hypoxia as saturation
      <80% or a decrease in saturation >10% from baseline. RESULTS: There were 538 NCPs
      in 154 Fontan patients (mean age, 30 years) performed in 1990-2015. Sedation and
      anaesthesia types were monitored anaesthesia care (256,48%), general anaesthesia
      (51,9%), minimal sedation (105,20%), local anaesthesia (75,14%) and regional
      anaesthesia (51,9%). Ninety-three complications occurred in 79 procedures (15%)
      and included arrhythmia requiring intervention (9), hypotension (14), bradycardia
      (8), hypoxia (38), heart failure requiring intravenous diuretics (2), acute
      kidney injury (3), bleeding requiring blood transfusion (1), unplanned procedures
      for dialysis catheter placement (2), readmission (2), unplanned hospitalisation
      for hypoxia (8) and unplanned transfer to intensive care unit (1). Baseline
      cyanosis was the only multivariable risk factor for complications (HR, 1.87 (95%
      CI 1.14 to 3.67), p=0.04). Procedural complications were more common in the
      Fontan group (18%) than in the CHD-BiV (5%) and NHD groups (1.4%) (p=0.001).
      CONCLUSIONS: Complications after NCPs were more common in Fontan patients, and
      baseline cyanosis was a risk factor for complications. All-cause mortality was
      low and may be related to the multidisciplinary care approach used for Fontan
      patients at our centre.

PMID- 28501798
TI  - Dose-time-response association between occupational asbestos exposure and pleural
      mesothelioma.
AB  - OBJECTIVES: Early occupational exposure to asbestos has been shown to be
      associated with an increased risk of pleural mesothelioma (PM), which suggests
      that the timing of exposure might play a role in the dose-response relationship.
      However, none studies has evaluated the relative impact of increasing the annual
      intensity of occupational exposure to asbestos at each time of the whole exposure
      history. Yet such evaluation would allow the comparison of the risks of PM
      associated with different longitudinal profiles of occupational exposure to
      asbestos. Our objective was to estimate the time-dependent relative impact of
      asbestos exposure intensity over the whole occupational history and to compare
      the resulting estimated risks of PM associated with different profiles of
      exposure, using data from a large French case-control study. METHODS: This study
      included 1196 male cases recruited in 1987-2006 and 2369 matched controls on
      birth year. Occupational exposure to asbestos was assessed using a job exposure
      matrix and represented in logistic regression models using a flexible weighted
      cumulative index of exposure. RESULTS: Due to much stronger weights of early
      doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their
      entire job history with high doses during the first years and low doses
      thereafter were at higher risk of PM than those who accumulated most of the doses
      later (OR=2.37 (95% CI 2.01 to 2.87)). CONCLUSION: This study provides new
      insights on the dose-time-response relationship between occupational asbestos and
      PM and illustrates the importance of considering timing of exposure in its
      association with cancer risk.

PMID- 28501800
TI  - Ustekinumab inhibits Th1 and Th17 polarisation in a patient with giant cell
      arteritis.

PMID- 28501799
TI  - High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type
      I interferon signature is a risk factor for the development of autoimmune
      congenital heart block.
AB  - OBJECTIVES: Autoimmune congenital heart block (CHB) is associated with placental
      transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B.
      However, only about 2% of children born to mothers with the respective antibodies
      are affected, indicating that further risk factors exist, which are not yet fully
      understood. In this study, we investigated whether a maternal type I interferon
      (IFN) signature represents a risk factor for the development of CHB. METHODS:
      Blood samples, clinical data and serological parameters from 9 women with CHB
      pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB
      complication and another 30 healthy pregnant women as controls were studied.
      SIGLEC1 expression was measured by flow cytometry and was correlated to plasma
      IFN-alpha levels measured by ELISA, and IFN-gamma-induced protein 10 (IP-10)
      levels measured by Bio-Plex technique. RESULTS: Mothers of affected children had
      a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-alpha (p=0.014),
      but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children.
      SIGLEC1 and IFN-alpha expression were reduced by hydroxychloroquine and oral
      glucocorticoids. CONCLUSIONS: High expression of SIGLEC1 in pregnant women with
      autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development,
      and these women may benefit especially from IFN-alpha directed therapy, for
      example with hydroxychloroquine.

PMID- 28501801
TI  - A rare coding allele in IFIH1 is protective for psoriatic arthritis.
AB  - OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory arthritis associated
      with psoriasis. While many common risk alleles have been reported for association
      with PsA as well as psoriasis, few rare coding alleles have yet been identified.
      METHODS: To identify rare coding variation associated with PsA risk or
      protection, we genotyped 41 267 variants with the exome chip and investigated
      association within an initial cohort of 1980 PsA cases and 5913 controls.
      Genotype data for an independent cohort of 2234 PsA cases and 5708 controls was
      also made available, allowing for a meta-analysis to be performed with the
      discovery dataset. RESULTS: We identified an association with the rare variant
      rs35667974 (p=2.39x10-6, OR=0.47), encoding an Ile923Val amino acid change in the
      IFIH1 gene protein product. The association was reproduced in our independent
      cohort, which reached a high level of significance on meta-analysis with the
      discovery and replication datasets (p=4.67x10-10). We identified a strong
      association with IFIH1 when performing multiple-variant analysis (p=6.77x10-6),
      and found evidence of independent effects between the rare allele and the common
      PsA variant at the same locus. CONCLUSION: For the first time, we report a rare
      coding allele in IFIH1 to be protective for PsA. This rare allele has also been
      identified to have the same direction of effect on type I diabetes and psoriasis.
      While this association further supports existing evidence for IFIH1 as a causal
      gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1
      is indeed causal.

PMID- 28501803
TI  - Among opioid-naive patients receiving opioids, more intensive opioid prescribing
      in the first month is associated with transition to long-term opioid use.

PMID- 28501802
TI  - Stability of Proteins in Dried Blood Spot Biobanks.
AB  - An important motivation for the construction of biobanks is to discover
      biomarkers that identify diseases at early, potentially curable stages. This will
      require biobanks from large numbers of individuals, preferably sampled
      repeatedly, where the samples are collected and stored under conditions that
      preserve potential biomarkers. Dried blood samples are attractive for biobanking
      because of the ease and low cost of collection and storage. Here we have
      investigated their suitability for protein measurements. Ninety-two proteins with
      relevance for oncology were analyzed using multiplex proximity extension assays
      (PEA) in dried blood spots collected on paper and stored for up to 30 years at
      either +4  degrees C or -24  degrees C.Our main findings were that (1) the act of
      drying only slightly influenced detection of blood proteins (average correlation
      of 0.970), and in a reproducible manner (correlation of 0.999), (2) detection of
      some proteins was not significantly affected by storage over the full range of
      three decades (34 and 76% of the analyzed proteins at +4  degrees C and -24 
      degrees C, respectively), whereas levels of others decreased slowly during
      storage with half-lives in the range of 10 to 50 years, and (3) detectability of
      proteins was less affected in dried samples stored at -24  degrees C compared
      with at +4  degrees C, as the median protein abundance had decreased to 80 and
      93% of starting levels after 10 years of storage at +4  degrees C or -24  degrees
      C, respectively. The results of our study are encouraging as they suggest an
      inexpensive means to collect large numbers of blood samples, even by the donors
      themselves, and to transport, and store biobanked samples as spots of whole blood
      dried on paper. Combined with emerging means to measure hundreds or thousands of
      protein, such biobanks could prove of great medical value by greatly enhancing
      discovery as well as routine analysis of blood biomarkers.

PMID- 28501805
TI  - Neurological tests improve after Olympic-style boxing bouts: a pretournament and
      post-tournament study in the 2016 Women's World Boxing Championships.
AB  - AIM: To prospectively examine the neurocognitive, postural, dual-task and visual
      abilities of female Olympic-style boxers before and after participation in a
      tournament. METHODS: Sixty-one females completed the modified Balance Error
      Scoring System (mBESS), King-Devick test and 3 m timed-up-and-go test in single
      task and dual-task conditions. A subset (n=31) completed the CogState
      computerised neurocognitive test. Initial testing was completed prior to the 2016
      Women's World Boxing Championships; each participant repeated the testing
      protocol within a day of elimination. No participant sustained a concussion.
      Pretournament and post-tournament performance variables were compared using
      paired t-tests or Wilcoxon signed-rank tests. RESULTS: Participants completed a
      mean of 7.5+/-4.5 rounds of Olympic-style boxing over 2-8 days. Post-tournament
      scores were significantly lower than pretournament scores for total mBESS (2.2+/
      1.9 errors vs 5.5+/-2.9 errors, p<0.001, d=1.23) and King-Devick time (14.2+/-3.9
      s vs 18.0+/-8.3 s, p=0.002, d=0.53). Processing speed was significantly faster
      after the boxing tournament (maze chase task: 1.39+/-0.34 correct moves/second vs
      1.17+/-0.44 correct moves/second, p=0.001, d=0.58). No significant changes across
      time were detected for the other obtained outcome variables. CONCLUSIONS: Female
      boxers demonstrated either improvement or no significant changes in test
      performance after competing in an Olympic-style boxing tournament, relative to
      pretournament performance. As many of the test tasks were novel for the boxers,
      practice effects may have contributed to improved performance. When there is a
      short time frame between assessments, clinicians should be aware of potential
      practice effects when using ringside neurological tests.

PMID- 28501807
TI  - Unilateral papilloedema.

PMID- 28501808
TI  - Bureaucracy, trust and time: recruitment in a low-risk study of paediatric
      protocols forchildren who miss medicalappointments.

PMID- 28501804
TI  - Exercise and other non-pharmaceutical interventions for cancer-related fatigue in
      patients during or after cancer treatment: a systematic review incorporating an
      indirect-comparisons meta-analysis.
AB  - AIM: To assess the relative effects of different types of exercise and other non
      pharmaceutical interventions on cancer-related fatigue (CRF) in patients during
      and after cancer treatment. DESIGN: Systematic review and indirect-comparisons
      meta-analysis. DATA SOURCES: Articles were searched in PubMed, Cochrane CENTRAL
      and published meta-analyses. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
      Randomised studies published up to January 2017 evaluating different types of
      exercise or other non-pharmaceutical interventions to reduce CRF in any cancer
      type during or after treatment. STUDY APPRAISAL AND SYNTHESIS: Risk of bias
      assessment with PEDro criteria and random effects Bayesian network meta-analysis.
      RESULTS: We included 245 studies. Comparing the treatments with usual care during
      cancer treatment, relaxation exercise was the highest ranked intervention with a
      standardisedmean difference (SMD) of -0.77 (95% Credible Interval (CrI) -1.22 to 
      0.31), while massage (-0.78; -1.55 to -0.01), cognitive-behavioural therapy
      combined with physical activity (combined CBT, -0.72; -1.34 to -0.09), combined
      aerobic and resistance training (-0.67; -1.01 to -0.34), resistance training (
      0.53; -1.02 to -0.03), aerobic (-0.53; -0.80 to -0.26) and yoga (-0.51; -1.01 to
      0.00) all had moderate-to-large SMDs. After cancer treatment, yoga showed the
      highest effect (-0.68; -0.93 to -0.43). Combined aerobic and resistance training
      (-0.50; -0.66 to -0.34), combined CBT (-0.45; -0.70 to -0.21), Tai-Chi (-0.45; 
      0.84 to -0.06), CBT (-0.42; -0.58 to -0.25), resistance training (-0.35; -0.62 to
      -0.08) and aerobic (-0.33; -0.51 to -0.16) showed all small-to-moderate SMDs.
      CONCLUSIONS: Patients can choose among different effective types of exercise and
      non-pharmaceutical interventions to reduce CRF.

PMID- 28501806
TI  - Exercise in type 2 diabetes: genetic, metabolic and neuromuscular adaptations. A
      review of the evidence.
AB  - The biological responses to exercise training are complex, as almost all organs
      and systems are involved in interactions that result in a plethora of adaptations
      at the genetic, metabolic and neuromuscular levels.To provide the general
      practitioner and the sports medicine professionals with a basic understanding of
      the genetic, metabolic and neuromuscular adaptations at a cellular level that
      occur with aerobic and resistance exercise in subjects with type 2 diabetes.For
      each of the three domains (genetic, metabolic and neuromuscular), the results of
      the major systematic reviews and original research published in relevant
      journals, indexed in PubMed, were selected. Owing to limitations of space, we
      focused primarily on the role of skeletal muscle, given its pivotal role in
      mediating adaptations at all levels.Generally, training-induced adaptations in
      skeletal muscle are seen as changes in contractile proteins, mitochondrial
      function, metabolic regulation, intracellular signalling, transcriptional
      responses and neuromuscular modifications. The main adaptation with clinical
      relevance would include an improved oxidative capacity derived from aerobic
      training, in addition to neuromuscular remodelling derived from resistance
      training. Both training modalities improve insulin sensitivity and reduce
      cardiovascular risk.Taken together, the modifications that occur at the genetic,
      metabolic and neuromuscular levels, work correlatively to optimise substrate
      delivery, mitochondrial respiratory capacity and contractile function during
      exercise.

PMID- 28501809
TI  - Non-specific effects of vaccines: plausible and potentially important, but
      implications uncertain.
AB  - Non-specific effects (NSE) or heterologous effects of vaccines are proposed to
      explain observations in some studies that certain vaccines have an impact beyond
      the direct protection against infection with the specific pathogen for which the
      vaccines were designed. The importance and implications of such effects remain
      controversial. There are several known immunological mechanisms which could lead
      to NSE, since it is widely recognised that the generation of specific immunity is
      initiated by non-specific innate immune mechanisms that may also have wider
      effects on adaptive immune function. However, there are no published studies that
      demonstrate a mechanistic link between such immunological phenomena and
      clinically relevant NSE in humans. While it is highly plausible that some
      vaccines do have NSE, their magnitude and duration, and thus importance, remain
      uncertain. Although the WHO recently concluded that current evidence does not
      justify changes to immunisation policy, further studies of sufficient size and
      quality are needed to assess the importance of NSE for all-cause mortality. This
      could provide insights into vaccine immunobiology with important implications for
      infant health and survival.

PMID- 28501810
TI  - Alveolar rhabdomyosarcoma in a 6-month-old boy.

PMID- 28501811
TI  - Haemodynamic analysis for recanalisation of intracranial aneurysms after
      endovascular treatment: an observational registry study in China.
AB  - INTRODUCTION: Recanalisation of intracranial aneurysms following endovascular
      treatment is a major issue. Many factors, including aneurysm morphology, the
      method of treatment, and haemodynamics, are considered to be associated with
      recanalisation. However, the underlying haemodynamic mechanisms are not
      completely understood. METHODS AND ANALYSIS: This is a prospective,
      observational, registry study for patients with intracranial aneurysms who are
      treated endovascularly. It will enrol 200 eligible patients. Data on
      morphological, haemodynamic, and treatment factors will be collected
      prospectively. The advanced virtual stenting technique and porous media method
      will be used in haemodynamic simulations. The clinical and angiographic outcomes
      at 6 months will be measured and analysed. This observational study will
      determine the haemodynamic factors that affect the recanalisation of aneurysms.
      ETHICS AND DISSEMINATION: Both the study protocol and written informed consent
      were reviewed and approved by the Institutional Review Board of Beijing Tiantan
      Hospital (KY2016-023-01). The results of study will be disseminated in
      professional printed media. TRIAL REGISTRATION NUMBER: NCT02812108; Pre-results.

PMID- 28501812
TI  - Integrating culturally informed approaches into the physiotherapy assessment and
      treatment of chronic pain: protocol for a pilot randomised controlled trial.
AB  - INTRODUCTION: There is strong evidence that biopsychosocial approaches are
      efficacious in the management of chronic pain. However, implementation of these
      approaches in clinical practice is known not to account for the beliefs and
      values of culturally and linguistically diverse (CALD) patients. This limitation
      in translation of research contributes to the disparities in outcomes for CALD
      patients with chronic pain adding to the socioeconomic burden of this prevalent
      condition. Cultural adaptation of chronic pain assessment and management is
      urgently required. Thus, the aim of this pilot randomised controlled trial (RCT)
      is to determine the feasibility, participant acceptance with and clinical
      effectiveness of a culturally adapted physiotherapy assessment and treatment
      approach when contrasted with 'usual evidence based physiotherapy care' for three
      CALD communities. METHODS AND ANALYSIS: Using a participant-blinded and assessor
      blinded randomised controlled pilot design, patients with chronic pain who self
      identify as Assyrian, Mandaean or Vietnamese will be randomised to either
      'culturally adapted physiotherapy assessment and treatment' or 'evidence informed
      usual physiotherapy care'. We will recruit 16 participants from each
      ethnocultural community that will give a total of 24 participants in each
      treatment arm. Both groups will receive physiotherapy treatment for up to 10
      sessions over 3 months. Outcomes including feasibility data, acceptance with the
      culturally adapted intervention, functional and pain-related measures will be
      collected at baseline and 3 months by a blinded assessor. Analysis will be
      descriptive for feasibility outcomes, while measures for clinical effectiveness
      will be explored using independent samples t-tests and repeated measures analysis
      of variance. This analysis will inform sample size estimates while also allowing
      for identification of revisions in the protocol or intervention prior to a larger
      scale RCT. ETHICS AND DISSEMINATION: This trial has full ethical approval
      (HREC/16/LPOOL/194). The results from this pilot RCT will be presented at
      scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION
      NUMBER: ACTRN12616000857404.

PMID- 28501813
TI  - The relationship between job satisfaction, work stress, work-family conflict, and
      turnover intention among physicians in Guangdong, China: a cross-sectional study.
AB  - OBJECTIVE: To investigate the relationship between job satisfaction, work stress,
      work-family conflict and turnover intention, and explore factors associated with
      turnover intention, among physicians in Guangdong Province, China. METHODS: From
      August to October 2013, physicians completed questionnaires and scales with
      regard to their job satisfaction, work stress, work-family conflict, and turnover
      intention. Binary logistic regression and structural equation modelling (SEM)
      were used in data analysis. RESULTS: A total of 3963 physicians were approached,
      with 3563 completing the questionnaire. The mean score of the overall perception
      of turnover intention of physicians who worked in Guangdong was 2.71 on a scale
      ranging from 1 to 6. Hours worked per week, working in an urban/rural area, type
      of institution, and age significantly impacted on turnover intention. Turnover
      intention was directly and negatively related to job satisfaction, and it was
      directly, indirectly and positively related to work stress and work-family
      conflict. CONCLUSION: Job satisfaction, work stress, work-family conflict, hours
      worked per week, working in an urban/rural area, types of institution and age are
      influencing factors of turnover intention. Reducing working hours, raising
      salary, providing more opportunities for career development and training,
      supporting and encouraging physicians by senior managers could potentially
      contribute to the reduction in turnover intention.

PMID- 28501814
TI  - A scoping review protocol on social participation of indigenous elders,
      intergenerational solidarity and their influence on individual and community
      wellness.
AB  - INTRODUCTION: Indigenous elders have traditionally played an important role in
      maintaining social cohesion within their communities. Today, part of this role
      has been taken over by government social and healthcare services, but they are
      having limited success in addressing social challenges. Increasing elders' social
      participation and intergenerational solidarity might foster community development
      and benefit young people, families, communities and the elders themselves.
      However, knowledge of the contribution of elders' social participation and
      intergenerational solidarity to wellness is scattered and needs to be
      synthesised. This protocol presents a scoping review on the social participation
      of indigenous elders, intergenerational solidarity and their influence on
      individual and community wellness. METHODS AND ANALYSIS: This scoping review
      protocol is based on an innovative methodological framework designed to gather
      information from the scientific and grey literature and from indigenous sources.
      It was developed by an interdisciplinary team including indigenous
      scholars/researchers, knowledge users and key informants. In addition to
      searching information databases in fields such as public health and indigenous
      studies, an advisory committee will ensure that information is gathered from grey
      literature and indigenous sources. ETHICS: The protocol was approved by the
      Ethics Review Board of the Universite du Quebec en Abitibi-Temiscamingue and the
      First Nations of Quebec and Labrador Health and Social Services Commission.
      DISCUSSION: The comprehensive synthesis of the scientific and grey literature and
      indigenous sources proposed in this protocol will not only raise awareness within
      indigenous communities and among healthcare professionals and community
      organisations, but will also enable decision-makers to better meet the needs of
      indigenous people. CONCLUSION: The innovative methodological framework proposed
      in this scoping review protocol will yield richer information on the contribution
      of elders to community wellness. This work is an essential preliminary step
      towards developing research involving indigenous communities, drawing on the
      social participation of elders and intergenerational solidarity.

PMID- 28501815
TI  - Can the prehospital National Early Warning Score identify patients most at risk
      from subsequent deterioration?
AB  - INTRODUCTION: The National Early Warning Score (NEWS) aids the early recognition
      of those at risk of becoming critically ill. NEWS has been recommended for use by
      ambulance services, but very little work has been undertaken to date to determine
      its suitability. This paper examines whether a prehospital NEWS derived from
      ambulance service clinical observations is associated with the hospital ED
      disposition. METHODS: Prehospital NEWS was retrospectively calculated from the
      ambulance service clinical records of 287 patients who were treated by the
      ambulance service and transported to hospital. In this cohort study, derived NEWS
      scores were compared with ED disposition data and patients were categorised into
      the following groups depending on their outcome: discharged from ED, admitted to
      a ward, admitted to intensive therapy unit (ITU) or died. RESULTS: Prehospital
      NEWS-based ambulance service clinical observations were significantly associated
      with discharge disposition groups (p<0.001), with scores escalating in line with
      increasing severity of outcome. Patients who died or were admitted to ITU had
      higher scores than those admitted to a ward or discharged from ED (mean NEWS 7.2
      and 7.5 vs 2.6 and 1.7, respectively), and in turn those who were admitted to a
      ward had higher pre-hospital NEWS than those who were discharged (2.6 vs 1.7).
      CONCLUSION: Our findings suggest that the NEWS could successfully be used by
      ambulance services to identify patients most at risk from subsequent
      deterioration. The implementation of this early warning system has the potential
      to support ambulance clinician decision making, providing an additional tool to
      identify and appropriately escalate care for acutely unwell patients.

PMID- 28501817
TI  - Putting the Wnt up colon cancer.

PMID- 28501816
TI  - Emergency medicine pharmacists on an international scale.

PMID- 28501819
TI  - Six issues in muscle disease.

PMID- 28501820
TI  - IgM MGUS and Waldenstrom-associated anti-MAG neuropathies display similar
      response to rituximab therapy.

PMID- 28501823
TI  - Cerebellar atrophy in neurodegeneration-a meta-analysis.
AB  - INTRODUCTION: The cerebellum has strong cortical and subcortical connectivity,
      but is rarely taken into account for clinical diagnosis in many neurodegenerative
      conditions, particularly in the absence of clinical ataxia. The current meta
      analysis aims to assess patterns of cerebellar grey matter atrophy in seven
      neurodegenerative conditions (Alzheimer's disease (AD), Parkinson's disease (PD)
      and Huntington's disease (HD), frontotemporal dementia (FTD), amyotrophic lateral
      sclerosis (ALS), multiple system atrophy (MSA), progressive supranuclear palsy
      (MSP)). METHODS: We carried out a systematic search in PubMed (any date: 14 July
      2016) and a hand search of references from pertinent articles according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. The authors were contacted to provide missing coordinate data. Peer
      reviewed studies with direct comparison of patient and control groups, and
      availability of coordinate data of grey matter cerebellar atrophy in patients
      were included. These coordinates were used in an anatomical likelihood estimation
      meta-analysis. RESULTS: Across 54 studies, clusters of cerebellar atrophy were
      found for AD, ALS, FTD, MSA, and PSP. Atrophy patterns were largely disease
      specific, with overlap in certain areas of the cerebellar hemisphere, which
      showed marked atrophy in AD, ALS, FTD and PSP (Crus I/II), and MSA and PSP
      (lobules I-IV), respectively. Atrophy colocated with cerebellar areas implicated
      for motor (PSP, MSA) or cognitive symptoms (FTD, ALS, PSP) in the diseases.
      DISCUSSION: Our findings suggest that cerebellar changes are largely disease
      specific and correspond to cortical or subcortical changes in neurodegenerative
      conditions. High clinical variability in PD and HD samples may explain the
      absence of findings for consistent grey matter loss across studies. Our results
      have clinical implications for diagnosis and cerebellar neuroimaging referencing
      approaches.

PMID- 28501822
TI  - Structural MRI correlates of amyotrophic lateral sclerosis progression.
AB  - PURPOSE: Amyotrophic lateral sclerosis (ALS) presents with varying degrees of
      brain degeneration that can extend beyond the corticospinal tract (CST).
      Furthermore, the clinical course and progression of ALS varies widely. Brain
      degeneration detected using structural MRI could reflect disease progression.
      SUBJECTS AND METHODS: On study registration, 3-Tesla volumetric MRI and diffusion
      tensor imaging scans were obtained at baseline in 38 healthy controls and 67
      patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional
      Rating Scale-Revised (ALSFRS-R) scores of >=36 and did not have the chromosome 9,
      open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R
      (DeltaALSFRS-R) scores were calculated and patients were grouped into three
      categories, namely, patients with slow progression with DeltaALSFRS-R scores <=3
      (n=19), intermediate progression with DeltaALSFRS-R scores =4, 5 and 6 (n=36) and
      rapid progression with DeltaALSFRS-R scores >=7 (n=12). We analysed voxel-based
      morphometry and tract-based spatial statistics among these subgroups and
      controls. RESULTS: In comparison with controls, patients with ALS showed grey
      matter atrophy and decreased fractional anisotropy beyond the motor cortex and
      CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the
      degree of change was highly proportional to DeltaALSFRS-R at the 6-month
      assessment. CONCLUSION: A more rapid disease progression and poorer functional
      decline were associated with greater involvement of the extra-motor cortex and
      basal ganglia, suggesting that the spatial extent of brain involvement can be an
      indicator of the progression in ALS.

PMID- 28501821
TI  - Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease.
AB  - OBJECTIVES: To analyse and describe the clinical and genetic spectrum of Charcot
      Marie-Tooth disease (CMT) caused by mutations in the neurofilament light
      polypeptide gene (NEFL). METHODS: Combined analysis of newly identified patients
      with NEFL-related CMT and all previously reported cases from the literature.
      RESULTS: Five new unrelated patients with CMT carrying the NEFL mutations P8R and
      N98S and the novel variant L311P were identified. Combined data from these cases
      and 62 kindreds from the literature revealed four common mutations (P8R, P22S,
      N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50
      (75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large
      myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and
      'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of
      them. The neurophysiological phenotype was broad but most patients with E90K and
      N98S had upper limb motor conduction velocities <38 m/s. Age of onset was <=3
      years in 25 cases. Pyramidal tract signs were described in 13 patients and 7
      patients were initially diagnosed with or tested for inherited ataxia. Patients
      with E90K and N98S frequently presented before age 3 years and developed hearing
      loss or other neurological features including ataxia and/or cerebellar atrophy on
      brain MRI. CONCLUSIONS: NEFL-related CMT is clinically and genetically
      heterogeneous. Based on this study, however, we propose mutational hotspots and
      relevant clinical-genetic associations that may be helpful in the evaluation of
      NEFL sequence variants and the differential diagnosis with other forms of CMT.

PMID- 28501825
TI  - Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with
      pre-eclampsia.
AB  - A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW)
      28-6/7 Cardiac status was checked regularly. Heart rate of 93 beats per minute
      (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and
      inferior vena cava diameter (IVCD) of 8 mm at GW 32-0/7 decreased to 48 bpm with
      an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased
      pulmonary arterial pressure, increased systemic vascular resistance (approximate
      3000  dyn s/cm5) and biphasic intrarenal venous flow pattern 3.5 hours prior to
      childbirth at GW 32-3/7 Epigastralgia, tachycardia (160 bpm) and marked
      hypertension (201/111 mm Hg) occurring 2 hours after echocardiography
      necessitated caesarean section, with subsequent development of HELLP syndrome.
      Acute fluid shift from the splanchnic vasculature to central vasculature may have
      occurred causing HELLP syndrome as a result from vasospasm associated with
      sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains
      unclear.

PMID- 28501824
TI  - The vanishing duodenal polyp: mesenteric invagination presenting as duodenal
      pseudopolyp.
AB  - Duodenal polypoid masses are an uncommon finding mainly diagnosed incidentally at
      endoscopy or surgery. We report a 39-year-old female patient with symptoms of
      intermittent stabbing pain in the upper right abdominal quadrant and an iron
      deficiency anaemia, without complaints of weight loss, haematemesis or melaena. A
      duodenal polyp and acute duodenitis have been described during endoscopic
      examinations and CT and ultrasound. Surgical excision of the polyp was advised.
      Intraoperatively, an elongated duodenum was remarkable; however, at duodenotomy,
      no polyp was found, nor during intraoperative endoscopy. Looking back at the
      endoscopy and imaging results, it was noted that the polyp varied in size and
      location. It was therefore concluded that we dealt with the pseudopolyp
      phenomenon, caused by invagination of the duodenal wall and its mesentery into
      the duodenum, presenting as a lipomatous pseudopolyp. Telescopic invagination of
      the duodenal wall was facilitated by the elongated hypermobile duodenum.

PMID- 28501826
TI  - Urothelial papilloma: a rare cause of gross haematuria in childhood.
AB  - Bladder urothelial papilloma is extremely rare in the paediatric population. It
      usually presents as painless gross haematuria and its diagnosis implies a high
      index of suspicion as other causes of haematuria predominate in this age range.
      We describe a 9-year-old boy with two episodes of gross haematuria occurring 1
      year apart with spontaneous resolution after 2 days. Bladder ultrasound revealed
      an endovesical papillary lesion of 24*24 mm suggestive of bladder tumour. The
      diagnosis was confirmed by histopathological examination of the specimen obtained
      by cystoscopy with transurethral resection. After 3 years of follow-up with
      ultrasound and cystoscopy, there are no signs of recurrence. Due to the low
      prevalence of urothelial papilloma, paediatric guidelines for appropriate
      management and follow-up are unavailable, making this a challenging entity.

PMID- 28501827
TI  - A confirmed case of sugammadex-induced anaphylaxis in a UK hospital.
AB  - We report the first published case of confirmed anaphylaxis to sugammadex in a UK
      hospital. The patient was given a bolus of sugammadex at the end of surgery. Four
      minutes later, he developed hypotension and a widespread erythematous rash.
      Multiple epinephrine boluses were administered and a continuous intravenous
      infusion of epinephrine commenced. The patient later reported auditory awareness,
      which occurred while the diagnosis of anaphylaxis was being made and initial
      treatment initiated. Serial serum tryptase levels were consistent with a type I
      hypersensitivity reaction. Skin prick and intradermal testing were performed 6
      months later confirming allergy to sugammadex. This case restates the potential
      for hypersensitivity reactions to develop following the administration of
      sugammadex and makes clinicians aware that such reactions may require prolonged
      treatment with intravenous infusions of epinephrine. Finally, this case
      highlights the importance of maintaining or re-establishing anaesthesia while
      managing the emergent situation in order to avoid unintentional awareness.

PMID- 28501829
TI  - Genetic causes of optic nerve hypoplasia.
AB  - Optic nerve hypoplasia (ONH) is the most common congenital optic nerve anomaly
      and a leading cause of blindness in the USA. Although most cases of ONH occur as
      isolated cases within their respective families, the advancement in molecular
      diagnostic technology has made us realise that a substantial fraction of cases
      has identifiable genetic causes, typically de novo mutations. An increasing
      number of genes has been reported, mutations of which can cause ONH. Many of the
      genes involved serve as transcription factors, participating in an intricate
      multistep process critical to eye development and neurogenesis in the neural
      retina. This review will discuss the respective genes and mutations, human
      phenotypes, and animal models that have been created to gain a deeper
      understanding of the disorders. The identification of the underlying gene and
      mutation provides an important step in diagnosis, medical care and counselling
      for the affected individuals and their families. We envision that future research
      will lead to further disease gene identification, but will also teach us about
      gene-gene and gene-environment interactions relevant to optic nerve development.
      How much of the functional impairment of the various forms of ONH is a reflection
      of altered morphogenesis versus neuronal homeostasis will determine the prospect
      of therapeutic intervention, with the ultimate goal of improving the quality of
      life of the individuals affected with ONH.

PMID- 28501828
TI  - Vedolizumab: a novel medical intervention in the treatment of primary sclerosing
      cholangitis.

PMID- 28501830
TI  - Views of Japanese medical students on the work-life balance of female physicians.
AB  - Objectives: To survey medical students on their ideas of future work-life balance
      and discuss topics for next-generation medical education. Methods: First-year
      (n=372, 34.9% female) and sixth-year medical students (n=311, 44.1% female)
      responded to a questionnaire on future self, marriage and childcare, and gender
      differences at the workplace. Responses were compared between academic years and
      gender. Responses were evaluated by gender and academic year using the Mann
      Whitney U test.  Significance was set at p<0.01. Results: The first-year and
      sixth-year students, regardless of gender, had different views on gender-related
      favorable treatment at workplaces {U=13464, p=0.000 (first-year), U=10407,
      p=0.000 (sixth-year)}. A greater percentage of female students would choose
      career options based on the possibility of marriage and childbirth {U=10689,
      p=0.000 (first-year), U=10930, p=0.000 (sixth-year)}. Among first-year students,
      a greater percentage of female students expected to work part-time. Also among
      first-year students, greater percentages of female students expected to work part
      time or leave their jobs temporarily while raising their children. Compared with
      first-year male students, first-year female students expected to undertake larger
      portions of the childcare and housework burden than their partners. However,
      gender differences in work-life balance and childcare leave vanished in the sixth
      year students. Conclusions: Female medical students accepted childcare and
      housework burdens as inevitable; the work environment they choose might affect
      their career development. While support from male partners and institutions must
      be increased, voluntary actions and change in mentality of female students need
      to be promoted through medical education to prevent them from waiting passively
      for the situation to change.

PMID- 28501832
TI  - [Features of autonomic dysfunction in myofascial pain syndromes cervicobrachial
      localization].
AB  - INTRODUCTION: The relevance of this study is due to the prevalence of autonomic
      disorders and musculoskeletal pain, especially among the young people of working
      age. In recent years, many authors in scientific works have been highlighted
      aspects of mutual development myofascial and autonomic dysfunction, which is
      caused by neurophysiological preconditions and anatomical and topographical
      relationships that need to be considered in the diagnostic and therapeutic
      approaches. OBJECTIVE: To study the characteristics of the formation and flow of
      autonomic dysfunction syndrome with paroxysmal and permanent types of flow in
      patients with myofascial pain syndromes cervicobrachial localization. MATERIAL
      AND METHODS: Using clinical neurological, vertebral neurological,
      neuropsychological methods of studying the severity of pain (visual analogue
      scale and Pain questionnaire of Mac Gill) examined 84 patients suffering from
      autonomic dysfunction on the background of myofascial pain syndromes
      cervicobrachial localization. To identify the features of vegetative regulation
      of patients were divided into two groups: group 1 (51 people) - with a permanent
      type of course; group 2 (33 patients) - a type of paroxysmal of course of
      autonomic dysfunction. RESULTS: It was found more pronounced disturbances in
      patients with paroxysmal type of course of autonomic dysfunction. The frequency
      and severity of autonomic paroxysms associated with the severity of musculo-tonic
      syndrome and location of active trigger points in the muscles of the neck and
      shoulder girdle, due to anatomic and topographic features of these muscles,
      namely the proximity of their location to the sympathetic formations neck. The
      formation and development of emotional and affective disorders in both groups
      played a significant role of pain and musculo-tonic syndrome. The syndrome of
      autonomic dysfunction, in particular its paroxysmal type of flow, on the one hand
      is a response to the development of myofascial pain syndromes cervicobrachial
      localization, with another - a factor that facilitates the development of pain
      and muscular-tonic syndromes, burdening the disease. CONCLUSION: In the diagnosis
      and treatment of myofascial and autonomic dysfunction should take into account
      comorbidity data of pathological conditions, which is important for developing
      individual therapeutic regimens.

PMID- 28501831
TI  - Resident attendance at weekly conferences after implementation of an optional
      asynchronous learning curriculum.

PMID- 28501833
TI  - [Psychometric and neurophysiological assessment of cognitive functions in
      patients with epilepsy].
AB  - BACKGROUND: The aim of the study was to assess cognitive functions in patients
      with epilepsy using the neurophysiological method and psychological tests, and
      analysis the relationship between clinical features of the disease and test
      results. MATERIAL AND METHODS: The study included 31 patients with epilepsy aged
      37.3+/-18.4 years. The control group consisted of 40 healthy volunteers aged
      33.5+/-12.2 years. Cognitive functions were assessed using endogenous evoked
      potential P300 and psychological tests - Mini-Mental State Examination (MMSE),
      three subtests of Wechsler Adult Intelligence Scale-Revised (WAIS-R), Trail
      Making Test (TMT), Benton Visual Retention Test (BVRT) and State-Trait Anxiety
      Inventory (STAI). RESULTS: Epileptic patients achieved significantly lower scores
      in all, except STAI-1, psychological tests in relation to the controls. A
      correlation between age and TMT-A (p<0.050) and BVRT (p<0.050) was observed. The
      disease duration affected results of MMSE (p<0.050), TMT-B (p<0.050) and BVRT
      (p<0.050). Type of seizures was related to results of MMSE (p=0.005), type of
      therapy - to results of STAI-1 (p=0.014) and TMT-B (p=0.008). The average latency
      of P300 was significantly prolonged (p=0.00003) in epileptic patients (348+/
      38ms) in relation to the controls (324+/-26ms). The relationship between P300 and
      the duration of seizures (p=0.017) was observed. There was no correlation between
      P300 and age, sex, frequency and type of seizures and therapy. A correlation
      between P300 and TMT-B (p<0.050), BVRT-LPO(p<0.050) and STAI-1 (p<0.050) was
      noticed. CONCLUSION: In epileptic patients cognitive impairment is often found.
      It is advisable to perform regular neuropsychological testing; P300 can be used
      only as a preliminary assessment.

PMID- 28501834
TI  - [Etiology of bacterial infections and incidence of comorbidities in patients with
      tuberculosis, treated in Mazovian Treatment Centre of Tuberculosis and Lung
      Diseases during years 2012-2014].
AB  - INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by the
      Mycobacterium tuberculosis. Infection occurs mostly via inhalation, while the
      immune system is weakened. TB can take a pulmonary or extrapulmonary form.
      Treatment involves an intensive, long-term antimycobacterial multidrug therapy.
      TB cases are recorded on the worldwide scale. The morbidity in Poland varies
      territorially. AIM: The analysis of bacterial infections and comorbidities cases
      in the patients with TB, treated in Mazovian Treatment Centre of Tuberculosis and
      Lung Diseases (MCLChPiG) during years 2012-2014. MATERIALS AND METHODS: The study
      includes an analysis of 3093 cases of tuberculosis among MCLChPiG patients in
      years 2012-2014, taking into account the age and gender of patients, forms of the
      disease, bacterial superinfection in the course of TB (based on the results of
      microbiological tests) and concomitant diseases. RESULTS: The study showed that
      TB was more common in men (64.79%). Most cases have been diagnosed in the 50-65
      year age group (31.65%). The most common form of TB among MCLChPiG patients was a
      respiratory tract tuberculosis (96.61%), especially the pulmonary form (82.67%).
      Concomitant diseases were diagnosed in 244 patients (7.89%), wherein tumors
      (4.88%) were the most common ones. Bacterial superinfection in the course of TB
      was observed in 149 patients (4.82%). The most frequently isolated bacteria were
      H. influenzae (28.65%) and S. aureus (15.79%). CONCLUSIONS: Long-term
      antimycobacterial treatment leads to the weakening of the patient's immune
      system, which is a favorable condition for the development of bacterial
      infections. Superinfection can be associated with concomitant disease, where
      weakness of immunoresponsiveness increases the risk of developing TB. Bacteria
      isolated from superinfections in the course of TB are mostly a typical pathogens
      of the upper and lower respiratory tract.

PMID- 28501835
TI  - [Possibility of using saliva as a diagnostic test material in cardiovascular
      diseases].
AB  - INTRODUCTION: Civilizational nature of the cardiovascular diseases, their
      prevalence and social impact of complications resulting from late diagnosis force
      to seek new faster and cheaper diagnostic methods. THE AIM: To present a
      systematic review of the literature on studies of classical and new
      cardiovascular diseases' risk markers in saliva. MATERIAL AND METHODS: Used
      database Pubmed, Cochrane from 1980 to 2013 in search of clinical studies of
      diagnostic tests for saliva in diseases of the cardiovascular system. RESULTS:
      Saliva sampling for testing is done in a non-invasive and painless way, transport
      and storage procedures are simpler and less expensive than blood. The diagnostic
      tests necessary in the diagnosis and treatment of diseases of the cardiovascular
      system can be performed in saliva. So far, the most promising diagnostic tests
      are: hs CRP saliva, cortisol, CK-MB, troponin, myoglobin and other biomarkers of
      inflammation. CONCLUSIONS: Biomarkers of the cardiovascular diseases may be
      determined in saliva. The use of saliva in the diagnosis is possible and should
      be applied both to screening assays, as well as in epidemiological and clinical
      diagnostics.

PMID- 28501836
TI  - [Bacopa Monnieri - activity and applications in medicine].
AB  - Recently appeared medicinal preparations containing an extract of Bacopa
      monnieri. B. monnieri has been used in the Ayurvedic system of medicine for
      centuries, especially to enhance cognitive functions. Active compounds in this
      plant include numerous saponins type dammarane, mainly bacoside A and B,
      alkaloids and sterols. The pharmacological research of the extract of Bacopa
      monnieri support traditional uses of this plant. The results of so far clinical
      studies of the extract from B. monnieri, indicate to beneficial effect on memory,
      learning and concentration in adults, children and to improve in anxiety and
      depression after prolonged administration, although further clinical studies are
      needed to confirm medical indications. It has been found to be well tolerated.
      The present review summarizes current knowledge of mechanisms of actions also
      presents of dietary supplements with B. monnieri.

PMID- 28501837
TI  - [Hypochondria yesterday and today].
AB  - The publication aims to discuss hypochondriacal disorders. This paper presents
      the history of the concept of hypochondria from antiquity to modern times, also
      includes brief information regarding etiopathogenesis, etiology, classification
      and treatment of hypochondria with particular emphasis on psychotherapy. Our goal
      was to make the subject hypochondriacal disorders, as a disease entity often
      encountered in everyday medical practice.

PMID- 28501838
TI  - [Pituitary disorders in elderly patients].
AB  - The increase in life expectancy of about 30 years in the developed countries
      represents one of the most important achievements of the last hundred years.
      During aging, normal pituitary activity undergoes significant changes, reflecting
      the complex relationship between aging and endocrine systems. These alterations
      are postulated to be causally linked to human aging, possibly contributing to
      changes in body composition, bone structure, physical performance, cardiovascular
      system functions, and increased morbidity and mortality. Owing to age-dependent
      physiological changes in pituitary function, as well as coexistent chronic
      illness and polypharmacy, interpretation of pituitary function tests in older
      adults is more difficult than in the younger. As symptoms of pituitary disorders
      may overlap with what is considered to be ''normal aging,'' the presence of a
      pituitary disorder in the elderly may often go undiagnosed. Unrecognized and
      untreated pituitary disorders are associated with adverse outcomes that can be
      ameliorated or prevented by adequate therapy. This paper summarizes the present
      state of knowledge on the age-related changes in pituitary function, as well as
      discusses the etiology, clinical manifestation, diagnosis, and management of
      pituitary disorders in the elderly.

PMID- 28501839
TI  - [Undernutrition in chronic respiratory diseases].
AB  - Respiratory diseases such as asthma, COPD, lung cancer, infections, including
      also tuberculosis constitute the most frequent diseases in the word.
      Undernutrition frequently accompanies these diseases. Early diagnosis of
      malnutrition and implementation of appropriate treatment is very important. A
      nutritional interview and anthropometric examinations, such as body mass index,
      fat free mass and fat mass are used to diagnose it. Nutritional therapy affects
      the course and prognosis of these diseases. Diet should be individually adjusted
      to the calculated caloric intake that increases during exacerbation of disease,
      because of increased respiratory effort. Too large supply of energy can cause
      increase metabolism, higher oxygen consumption and PaCO2 increase each dangerous
      for patients with respiratory insufficiency. Main source of carbohydrates for
      these patients should be products with low glycemic index and with high dietary
      fiber contents. Large meals should be avoided since they cause rapid satiety,
      abdominal discomfort and have negative impact on the work of the respiratory
      muscles, especially of the diaphragm. Dietary supplements can be used in case of
      ineffectiveness of diet or for the patients with severe undernutrition.

PMID- 28501840
TI  - [The aging of the immune system].
AB  - The age-related deterioration of health condition associated with progressive
      impairment of innate and adaptive immunity was defined as the aging of the immune
      system (also known as immunosenescence). Many changes occur within the immune
      system with age, including in particular quantitative changes in populations and
      subpopulations of cells resulting in dysfunction of the immune system. Elderly
      patients often have chronic systemic low grade inflammation process which is an
      effect of the inflammatory mediators secretion. Changes in the levels of
      mediators have a negative impact on coexisting disease and body's ability to
      fight infections. The purpose of the paper is to characterize the changes in
      proportions and functions of immune cells during the aging.

PMID- 28501841
TI  - [Nelson's Syndrome].
AB  - Nelson's syndrome is a rare condition defined by enlargement of a pituitary
      adenoma following bilateral adrenalectomy for treatment of Cushing disease.
      Nelson's syndrome occurs at an incidence of 8-38% and is more frequent in younger
      people. This syndrome is characterized by skin hyperpigmentation and very high
      circulating levels of adrenocorticotrophic hormone. The pathophysiology of the
      disease is still not fully understood, and it is unknown what factors drive
      corticotroph cells in these patients. Presently, the syndrome is diagnosed at
      earlier stages and therefore its clinical manifestation is less typical than in
      the past. However, we can still find cases of full-blown Nelson's syndrome,
      resulting from massive tumor growth and dramatically increased production of
      adrenocorticotrophic hormone. Treatment of this syndrome largely consists of
      surgery and/or radiotherapy because of the limited effectiveness of
      pharmacotherapy. Although no guidelines have been published, it is reasonable to
      perform pituitary imaging and to assess adrenocorticotrophic hormone in all
      patients, particularly during the first years after bilateral adrenalectomy. The
      purpose of this paper is to review the current views on the etiopathogenesis,
      clinical presentation, diagnosis and treatment of Nelson's syndrome.

PMID- 28501842
TI  - [Isolated vesical endometriosis - a case report].
AB  - INTRODUCTION: Although endometriosis affects up to 15% of the female population
      with childbearing potential, isolated endometriosis of the urinary tract is not a
      frequent occurrence, as it involves only 1 to 2% of all endometriosis patients.
      The chronic pelvic pain syndrome ultimately related to endometriosis is often
      both a diagnostic and therapeutic challenge Materials and methods: This paper
      presents the case of a female patient reporting with severe urinary symptoms.
      Following cystoscopy and ultrasonography investigations, a suspected endometrioid
      lesion of the urinary bladder has been evidenced. The patient-reported pain was
      rated using a 10-point visual analogue scale (VAS). The patient has not received
      pharmacotherapy. RESULTS: A partial laparoscopic full-thickness excision of the
      urinary bladder wall with the evidenced lesion has been performed. The urinary
      bladder wall has been sutured using two layers of sutures applied by laparoscopy.
      Postoperative histopathology examination revealed a deep infiltrating
      endometriosis lesion of the urinary bladder wall. Following surgery, the
      patient's complaints have withdrawn completely, and no subsequent pharmacotherapy
      was instated. DISCUSSION AND CONCLUSIONS: Isolated endometriosis of the urinary
      tract, including the urinary bladder, is not a common pathology. Nevertheless, it
      should always be taken into account in patients with dysuria or symptoms
      suggestive of bladder malignancy. Total laparoscopic excision of the lesion
      remains the treatment of choice, and in most cases provides patients with
      complete withdrawal of symptoms, and only minimal incidence of recurrences, as
      well as limited risk of early and delayed complications.

PMID- 28501843
TI  - [Secondary osteoporosisn in boys with Alagille syndrome. Case report].
AB  - Alagille syndrome is a multiorgan disorder, which especially manifests itself
      with cholestasis, characteristic facial features, circulatory systems defects,
      defects of the front segment of the eye, dysplastic changes in bones and kidneys
      and impaired angiogenesis.The disease is caused by Jagged 1 gene mutation (JAG,
      20p12 chromosome) which encodes ligand for Notch receptor. JAG/ Notch signaling
      pathway plays important evolutionary role in cell differentiation in
      organogenesis process . JAG1 expression in numerous tissues leads to multiorganic
      manifestation. Jagged 1 expression is substantially important for skeleton growth
      and bone cells activity. Its malfunction may lead to spine and long bones
      abnormalities, neoplastic changes and osteoporosis. In this case report authors
      present clinical (long bone fractures) and biochemical manifestations and
      densitometric abnormalities ( decrease of bone mineral density) in 10 years old
      boy with Alagille syndrome. Densitometry is suggested to be a good method in
      early detection of mineralization disturbances in chronic cholestasis and
      permanent monitoring of changes in bone structure is also very important.

PMID- 28501844
TI  - [Diagnostics enigma: left ventricular noncompaction or systemic right ventricle?]
AB  - A case of congenitally corrected transposition of great arteries, a rare
      congenital heart defect diagnosed in an adult is presented and difficulties in
      differential diagnosis of congenital heart defects in the adults are described.
      The crucial point is proper interpretation of the echocardiography examination.

PMID- 28501845
TI  - Medical terminology: Its size and typology.
AB  - Medical terminology is one of the largest specialized terminologies and is
      estimated to contain over 250,000 items. Classification of medical terminology
      into six categories is proposed. The categories are as the following: (A) medical
      terms that are a part of general basic lexicon of average native speaker (0.02
      0.03 % of all terms), (B) specialized medical terms known by average physician
      (about 45 % of all terms), (C) highly-specialized terms of subspecialties (about
      15 % of all terms) (D) medical terms that primarily belong to other terminologies
      (e.g. biological, chemical, physical, statistical) (about 20 % of all terms), (E)
      medical slang (0.04-0.05 % of all terms), and (F) pharmaceutical terminology
      (about 20 % of all terms).

PMID- 28501846
TI  - [The 2nd conference 'Rare diseases not only in the curriculum', Szczecin -
      Wroclaw, 26 and 30 May 2015].
AB  - The 2nd conference 'Rare diseases not only in the curriculum', that took place on
      26th May, 2015 in Pomeranian Medical University in Szczecin and 30 May in Wroclaw
      Medical University. In accordance with the convention adopted at the first
      conference in 2014 in Szczecin participants of the meeting realized the idea
      expressed in the title of the conference by presenting issues of commonly known
      rare diseases and those that are not discussed in the course of medical studies.
      The active participants of the meeting were scientific workers medical schools in
      Szczecin, Wroclaw and Bialystok, medical students and PhD students. The
      significance of newborn screening in the early diagnosis of rare diseases in
      children, possibilities of supporting children with genetically conditioned rare
      diseases and their caregivers, application of guidelines of evidence-based
      medicine in the process of diagnosing non-routine patients and methods of
      physiotherapy of children with spinal muscular atrophy were discussed. Detailed
      issues of diagnosing and treatment of many rare diseases were also presented,
      among others Wilson disease, Alstrom syndrome, Cohen syndrome, Rubinstein-Taybi
      syndrome, Cornelia de Lange syndrome, Poland syndrome, Netherton syndrome, inborn
      aniridia and congenital arhinia - very rare defect requiring further scientific
      studies.

PMID- 28501847
TI  - [Activity Polish Physicians of Transcarpathian].
AB  - The article presents the history of founding of the Organisation of Polish
      Physicians of Transcarpathian and their participation in presentation of the
      achievements of Polish Medical Sciences in Ukraine.

PMID- 28501848
TI  - Mucinous adenocarcinoma and non-mucinous adenocarcinoma: differing
      clinicopathological characteristics and computed tomography features in gastric
      cancer.
AB  - Mucinous gastric carcinoma (MGC) is a rare histological subtype of gastric
      cancer. The clinicopathological characteristics and CT features of MGC remain
      controversial. This study aimed to determine the clinicopathological
      characteristics and CT features of MGC. We reviewed 62 patients with MGC and 104
      patients with non-mucinous gastric carcinoma (NMGC), pathologically confirmed
      between 2003 and 2015. There are significant differences in some
      clinicopathological characteristics and CT features between MGC and NMGC. NMGC
      occurs preferentially in males and more frequently in the lower third of the
      stomach. Patients with MGC were characterized by larger tumor size, more advanced
      tumor stages (II and III) and fewer lymphatic invasions. Layered enhancement
      (83.3%) was the main pattern of MGC, while the most common pattern in NMGC was
      homogeneous enhancement (52.6%), followed by heterogonous enhancement (34.6%).
      The degree of enhancement of the inner layer in MGC was significantly higher than
      in NMGC (DeltaCT of portal venous phase: 54.57 Hu vs. 47.19 Hu, P = 0.034), while
      the middle or outer layer in MGC was significantly less enhanced (DeltaCT of
      portal venous phase: 19.07 Hu vs. 33.09 Hu, P <0.001). Calcifications were more
      common in MGC (P <0.001). ROC curves revealed that the most effective variables
      in distinguishing MGC and NMGC were DeltaCT of the middle or outer layer in the
      arterial phase (AUC=0.774) and portal venous phase (AUC=0.774), followed by the
      attenuation value of the middle or outer layer in the unenhanced phase
      (AUC=0.763). Calcifications had a high specificity (98.7%) in the diagnosis of
      MGC. The accuracy (86.1%), sensitivity (83.3%) and specificity (87.2%) of layered
      enhancement in diagnosing MGC were all high. Therefore, MGC was more likely to
      have larger tumor size and more advanced tumor stage (II and III) than NMGC. The
      thicker gastric wall, layered enhancement pattern and calcification were highly
      suggestive CT features for differentiating MGC from NMGC.

PMID- 28501849
TI  - miR-551b regulates epithelial-mesenchymal transition and metastasis of gastric
      cancer by inhibiting ERBB4 expression.
AB  - Epithelial-mesenchymal transition (EMT) is an important biological process that
      is characteristic of malignant tumor cells with metastatic potential. We
      investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC).
      We found that low miR-551b levels were associated with EMT, metastasis and a poor
      prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901,
      exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing
      MNK45 and SGC7901 cells to TGF-beta1 resulted in cell morphology changes
      characteristic of EMT, which was confirmed by Western blot analysis demonstrating
      low E-Cadherin and high N-Cadherin and Vimentin levels. Treatment with miR-551b
      mimics inhibited these EMT changes as well as Transwell migration and
      invasiveness. We identified ERBB4 as a potential target of miR-551b based on
      patient data from the TCGA. ERBB4 was upregulated in GC specimens, and its high
      expression correlated with a poor prognosis of GC patients. Dual luciferase
      assays revealed that miR-551b directly inhibited ERBB4 by binding to its 3'UTR.
      Moreover, treatment with miR-551b mimics or the ERBB4 inhibitor AST-1306
      inhibited EMT in the GC cell lines. Finally, nude mice xenografted with GC cancer
      cell lines expressing miR-551b mimics exhibited smaller tumors and longer
      survival than mice engrafted with control GC cancer cells. These data indicate
      that miR-551b inhibits EMT and metastasis in GC by inhibiting ERBB4. miR-551b and
      ERBB4 are thus potential therapeutic targets for the treatment of GC.

PMID- 28501852
TI  - Clinically significant sub-clonality for common drivers can be detected in 26% of
      KRAS/EGFR mutated lung adenocarcinomas.
AB  - Genetic sub-clonality has been described in multiple malignancies, however the
      presence of sub-clonality for major drivers in lung adenocarcinoma and its
      clinical significance is a subject under debate. Using molecular and morphometric
      approach, 347 lung adenocarcinoma samples were analyzed for KRAS and EGFR sub
      clonality, which was further correlated with clinical and pathological
      variables.KRAS and EGFR mutations were identified in 100 (29%) and 82 (23%)
      cases, respectively. One hundred and forty four KRAS or EGFR positive cases were
      also available for morphometric analysis, among which 37 (26%) were defined as
      sub-clonal. The presence of sub-clonality was associated with shorter survival
      time (p=0.02). Interestingly, cases with sub-clonality were also associated with
      earlier disease stage (89% vs 66% stage I disease in sub-clonal vs clonal cases,
      respectively, p=0.01) and less lymph node involvement (8% vs 25% in sub-clonal vs
      clonal cases, respectively, p=0.02). Our findings demonstrate the presence of sub
      clonality for mutations in common drivers in lung adenocarcinoma and link it both
      to earlier disease stage and to poor survival. These findings are in line with
      the different evolutionary models that can present with genetic sub-clonality.

PMID- 28501851
TI  - Implementing liquid biopsies into clinical decision making for cancer
      immunotherapy.
AB  - During the last decade, novel immunotherapeutic strategies, in particular
      antibodies directed against immune checkpoint inhibitors, have revolutionized the
      treatment of different malignancies leading to an improved survival of patients.
      Identification of immune-related biomarkers for diagnosis, prognosis, monitoring
      of immune responses and selection of patients for specific cancer immunotherapies
      is urgently required and therefore areas of intensive research. Easily accessible
      samples in particular liquid biopsies (body fluids), such as blood, saliva or
      urine, are preferred for serial tumor biopsies.Although monitoring of immune and
      tumor responses prior, during and post immunotherapy has led to significant
      advances of patients' outcome, valid and stable prognostic biomarkers are still
      missing. This might be due to the limited capacity of the technologies employed,
      reproducibility of results as well as assay stability and validation of results.
      Therefore solid approaches to assess immune regulation and modulation as well as
      to follow up the nature of the tumor in liquid biopsies are urgently required to
      discover valuable and relevant biomarkers including sample preparation, timing of
      the collection and the type of liquid samples. This article summarizes our
      knowledge of the well-known liquid material in a new context as liquid biopsy and
      focuses on collection and assay requirements for the analysis and the technical
      developments that allow the implementation of different high-throughput assays to
      detect alterations at the genetic and immunologic level, which could be used for
      monitoring treatment efficiency, acquired therapy resistance mechanisms and the
      prognostic value of the liquid biopsies.

PMID- 28501854
TI  - Dual-negative expression of Nrf2 and NQO1 predicts superior outcomes in patients
      with non-small cell lung cancer.
AB  - Functional studies in non-small cell lung cancer (NSCLC) patients revealed that
      hyperactivation of the NF-E2-related factor 2 (Nrf2) pathway facilitates tumor
      growth. We examined the usefulness of Nrf2 and NQO1 as indicators of prognosis in
      NSCLC. Tumor and adjacent non-tumor tissue samples were collected from 215 NSCLC
      patients who had tumor resections between 2006 and 2011. Immunohistochemistry was
      performed to detect Nrf2 or NQO1 expression. The correlation between Nrf2 or NQO1
      expression and survival outcomes was evaluated using the Kaplan-Meier method and
      Cox proportional hazards regression model. Levels of Nrf2 and NQO1 were elevated
      in tumor tissues. In particular, Nrf2 was elevated in nearly all tumor cells.
      NQO1 expression positively correlated with Nrf2 expression (P = 0.039). Nrf2
      expression positively correlated with lymph node metastasis (P = 0.001) and
      negatively correlated with tumor differentiation (P = 0.032). As compared with
      either Nrf2 or NQO1 alone, dual-negative expression of Nrf2 and NQO1 was more
      predictive of superior overall survival (P = 0.020) and disease free survival (P
      = 0.037). Subgroup analyses showed that females, nonsmokers, and patients with
      advanced-stage NSCLC were suitable populations in which to evaluate prognosis
      based on Nrf2 and NQO1 co-expression. These results indicate that dual-negative
      expression of Nrf2 and NQO1 is predictive of a better prognosis in NSCLC
      patients.

PMID- 28501855
TI  - Extracellular pH is a biomarker enabling detection of breast cancer and liver
      cancer using CEST MRI.
AB  - Extracellular pH (pHe) decrease is associated with tumor growth, invasion,
      metastasis, and chemoresistance, which can be detected by chemical exchange
      saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we
      demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of
      the liver cancer microenvironment. In in vitro studies, we firstly explored
      whether ioversol signal is pH-dependent, and calculated the function equation
      between the CEST effects of ioversol and pH values, in the range of 6.0 to 7.8,
      by a ratiometric method. Then we verified the feasibility of this technique and
      the equation in vivo by applying pHe imaging in an MMTV-Erbb2 transgenic mouse
      breast cancer model, which is often used in CEST pHe studies. Furthermore, in
      vivo ioversol CEST MRI, we were able to map relative pHe and differentiate
      between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests
      pHe may be a useful biomarker for human liver cancer.

PMID- 28501856
TI  - Prognostic significance of subclassification of stage IIB lung cancer: a
      retrospective study of 226 patients.
AB  - We investigated the prognostic significance of subclassification of stage IIB
      lung cancer according to the eighth tumor-node-metastasis (TNM) classification.
      To this purpose, the prognostic outcomes of 226 stage IIB lung cancer patients
      who underwent surgery without adjuvant therapies between 2001 and 2010 were
      evaluated retrospectively based on the eighth TNM classification. Of the 226
      patients, 23, 30, 118 and 55 had pT1b, pT1c, pT2a, and pT2b stage cancers,
      respectively. Their 5-year survival rates were 67%, 33%, 21%, and 27%,
      respectively. There was no significant difference in the 5-year survival between
      T1b and T1c, between T1c and T2a, and between T2a and T2b (p = 0.128, 0.105, and
      0.403, respectively). There were significant differences in the 5-year survival
      between T1b and T2a, between T1b and T2b, and between T1c and T2b (p = 0.005,
      0.002, and 0.042, respectively). The 5-year survival of patients with pleural
      invasion and vessel invasion was significantly worse than that of their
      counterparts (p = 0.009 and <0.001, respectively). Subclassification of stage IIB
      lung cancer is of prominent prognostic significance. It is recommended that the
      current stage be subclassified, in order to more accurately predict the prognosis
      of patients.

PMID- 28501858
TI  - The Interdisciplinary Chronic Kidney Disease Clinic: End of the Beginning, Not
      Beginning of the End.

PMID- 28501859
TI  - Molecular Insights into Covalently Stained Carious Dentine Using Solid-State NMR
      and ToF-SIMS.
AB  - Dyes currently used to stain carious dentine have a limited capacity to
      discriminate normal dentine from carious dentine, which may result in
      overexcavation. Consequently, finding a selective dye is still a challenge.
      However, there is evidence that hydrazine-based dyes, via covalent bonds to
      functional groups, bind specifically to carious dentine. The aim of this study
      was to investigate the possible formation of covalent bonds between carious
      dentine and 15N2-hydrazine and the hydrazine-based dye, 15N2-labelled Lucifer
      Yellow, respectively. Powdered dentine from extracted carious and normal teeth
      was exposed to the dyes, and the staining reactions were analysed using time-of
      flight secondary ion mass spectrometry (ToF-SIMS), solid-state 13C-labelled
      nuclear magnetic resonance (NMR) and 15N-NMR spectroscopy. The results showed
      that 15N2-hydrazine and 15N2-labelled Lucifer Yellow both bind to carious dentine
      but not to normal dentine. It can thus be concluded that hydrazine-based dyes can
      be used to stain carious dentine and leave normal dentine unstained.

PMID- 28501857
TI  - Combined treatment with artesunate and bromocriptine has synergistic anticancer
      effects in pituitary adenoma cell lines.
AB  - Prolactinomas are the most prevalent functional pituitary adenomas. The preferred
      treatments for prolactinomas are dopamine agonists (DAs) such as bromocriptine
      (BRC), but DAs still have the challenges of tumor recurrence and drug resistance.
      This study demonstrates that the synergy of function and mechanism between
      artesunate (ART) and BRC inhibits prolactinoma cell growth in vitro. We found
      that low-dose ART combined with BRC synergistically inhibited the growth of GH3
      and MMQ cell lines, caused cell death, attenuated cell migration and invasion,
      and suppressed the expression of extracellular prolactin. The induction of
      apoptosis after co-treatment was confirmed by immunofluorescent staining,
      assessment of caspase-3 protein expression, and flow cytometry. Expression of miR
      200c, a carcinogenic factor in pituitary adenoma, was reduced following co
      treatment with ART and BRC. This was accompanied by increased expression of the
      antitumor factor Pten. Transfection experiments with miR-200c analogs and
      inhibitors confirmed that miR-200c expression was inversely associated with Pten
      expression. We suggest that ART and BRC used in combination exert synergistic
      apoptotic and antitumor effects by suppressing miR-200c and stimulating Pten
      expression.

PMID- 28501860
TI  - Single-Center Experience with Intimal Sarcoma, an Ultra-Orphan, Commonly Fatal
      Mesenchymal Malignancy.
AB  - BACKGROUND: Intimal sarcoma is a rare malignancy that, clinically and
      radiographically, often mimics pulmonary embolism. The intravascular tumor tends
      to disseminate rapidly and metastases can be present at first diagnosis. METHODS:
      We reviewed all cases of intimal sarcoma that were diagnosed, treated and
      followed at the University Hospitals Leuven between April 2006 and April 2016.
      RESULTS: We identified 13 patients with a median age of 51 years. In 6 patients
      initial findings were suggestive of thromboembolic disease. Platelet-derived
      growth factor receptor alpha (PDGFRA) amplification was the most prevalent
      molecular finding, present in 11 patients. The MDM2 gene was amplified in 9
      cases, and the EGFR gene in 3 patients. The median overall survival was 13
      months. 11 patients underwent surgery. In 5 cases with inoperable and/or
      metastatic disease chemotherapy was given. Treatment with imatinib was initiated
      in 4 patients. CONCLUSIONS: Intimal sarcoma is an extremely rare and aggressive
      malignancy that has a very poor prognosis. Mimicking thromboembolic disease,
      diagnosis and treatment can be delayed. Surgery is the mainstay of treatment but
      is seldom curative. The disease is highly resistant to cytotoxic and targeted
      treatment. Given the fact that intimal sarcoma commonly expresses more than 1
      molecular target, combination therapy might be an option, although toxicity may
      be a limitation.

PMID- 28501861
TI  - Pre-End-Stage Renal Disease Care and Early Survival among Incident Dialysis
      Patients in the US Military Health System.
AB  - BACKGROUND: Previous reports showed an increased early mortality after chronic
      dialysis initiation among the end-stage renal disease (ESRD) population. We
      hypothesized that ESRD patients in the Military Health System (MHS) would have
      greater access to pre-ESRD care and hence better survival rates during this early
      high-risk period. METHODS: In this retrospective cohort study, using the US Renal
      Data System database, we identified 1,256,640 patients initiated on chronic
      dialysis from January 2, 2004 through December 31, 2014, from which a bootstrap
      sample of 3,984 non-MHS incident dialysis patients were compared with 996 MHS
      patients. We assessed care by a nephrologist and dietitian, erythropoietin
      administration, and vascular access use at dialysis initiation as well as all
      cause mortality as outcome variables. RESULTS: MHS patients were significantly
      more likely to have had pre-ESRD nephrology care (adjusted OR [aOR] 2.9; 95% CI
      2.3-3.7) and arteriovenous fistula used at dialysis initiation (aOR 2.2; 95% CI
      1.7-2.7). Crude mortality rates peaked between the 4th and the 8th week for both
      cohorts but were reduced among MHS patients. The baseline adjusted Cox model
      showed significantly lower death rates among MHS vs. non-MHS patients at 6, 9,
      and 12 months. This survival advantage among MHS patients was attenuated after
      further adjustment for pre-ESRD nephrology care and dialysis vascular access.
      CONCLUSIONS: MHS patients had improved survival within the first 12 months
      compared to the general ESRD population, which may be explained in part by
      differences in pre-ESRD nephrology care and vascular access types.

PMID- 28501862
TI  - Chromosome Painting in Trogon s. surrucura (Aves, Trogoniformes) Reveals a
      Karyotype Derived by Chromosomal Fissions, Fusions, and Inversions.
AB  - Trogons are forest birds with a wide distribution, being found in Africa, Asia,
      and America, and are included in the order Trogoniformes, family Trogonidae.
      Phylogenetic studies using molecular data have not been able to determine the
      phylogenetic relationship among the different genera of trogons. So far, no
      cytogenetic data for these birds exist. Hence, the aim of this study was to
      characterize the karyotype of Trogon surrucura surrucura by means of classical
      and molecular cytogenetics. We found a diploid chromosome number of 2n = 82,
      similar to most birds, with several derived features compared to chicken and the
      putative ancestral avian karyotype. T. s. surrucura showed 3 pairs of
      microchromosomes bearing 18S rDNA clusters. The Z and W sex chromosomes were of
      similar size but could readily be identified by morphological differences. Using
      chromosome painting with whole chromosome probes from Gallus gallus and
      Leucopternis albicollis, we found that the chromosomes homologous to chicken
      chromosomes 2 and 5 correspond to 2 different pairs in T. s. surrucura and L.
      albicollis, due to the occurrence of centric fissions. Paracentric inversions
      were detected in the segment homologous to chicken chromosome 1q, and we
      confirmed the recurrence of breakpoints when our results were compared to other
      species of birds already analyzed by FISH or by in silico genome assembly.

PMID- 28501863
TI  - Psychometric Properties of the Revised Illness Perception Questionnaire for Oral
      Health.
AB  - AIMS: The aim of this study was to test the hypothesis that, for patients with
      dental caries, the Spanish version of the Revised Illness Perception
      Questionnaire for Oral Health (IPQ-R-OH) has 7 dimensions, including personal and
      treatment control, timeline-acute/chronic and timeline-cyclical, illness
      coherence, consequences, and emotional representations. METHODS: A Spanish
      adaptation of the IPQ-R, with a self-reported 38-item scale, was developed.
      Exploratory and confirmatory factor analyses were conducted using data from 520
      patients with dental caries attending the Dental Clinic at Universidad
      Cooperativa de Colombia, Pasto, Colombia. RESULTS: Exploratory factor analysis
      revealed 7 dimensions with 36 items (2 items were removed because of poor factor
      loadings or discriminant ability). The internal consistency coefficients of each
      factor ranged from 0.72 to 0.91, and all item loadings were >0.52. Confirmatory
      factor analysis indicated that a 7-factor model with 36 items had superior fit
      compared to the 38-item original model: chi2 = 1,784.291 (df = 573, p < 0.001);
      nonnormal fit index = 0.941; comparative fit index = 0.946; root mean square
      error of approximation = 0.062 (90% CI = 0.057-0.066); standardized root mean
      square residual = 0.072; and Akaike information criterion = 638.291. Control
      (integrated by items from personal control, treatment control, and timeline-acute
      factors) and hopelessness (PC15 and PC17) were the 2 reconfigured factors that
      were identified. CONCLUSIONS: These findings suggest that the modified 36-item
      model has satisfactory reliability and construct factorial validity; therefore,
      it could be a valuable instrument in the screening of illness perceptions in oral
      health.

PMID- 28501864
TI  - First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic
      Shock in the Era of Modern Ventricular Assist Devices.
AB  - OBJECTIVES: Little is known about circulatory support in cardiogenic shock (CS)
      from other causes than the acute coronary syndrome or after cardiotomy. We
      evaluated the effects of first-line intra-aortic balloon pump (IABP) support in
      this subpopulation of CS patients. METHODS: A retrospective study was performed
      in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in
      the years 2011-2016. RESULTS: At 24 h, lactate decreased from 3.2 (2.1-6.8) to
      1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP
      responders were successfully bridged to either recovery (n = 7), left ventricular
      assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9
      patients (non-responders, 33%) who either died (n = 7) or needed support by
      extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary
      output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and
      fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240]
      mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was
      63%. CONCLUSION: In most patients, first-line support by IABP in end-stage
      cardiomyopathy is associated with improvement in organ perfusion and clinical
      stabilisation for at least 24 h allowing time for decision making on next
      therapies.

PMID- 28501866
TI  - Clinical Factors Associated with Readmission among Patients with Lower Limb
      Cellulitis.
AB  - BACKGROUND: There is substantial allocation of resources directed towards
      evaluation and management of lower limb cellulitis (LLC) in the acute care
      setting. Readmission for LLC is poorly understood, and there is little evidence
      with which to identify patients at risk for readmission. OBJECTIVE: To describe
      demographics, comorbidities, admission vital signs, and laboratory markers of
      infection among patients with LLC who are readmitted, and to investigate which
      among these factors is associated with readmission. METHODS: A cross-sectional
      retrospective cohort study was performed at tertiary and community hospitals
      within a regional health care system in order to summarize readmission
      characteristics. Univariate and multivariate models were created to estimate the
      likelihood of independent variables being associated with LLC readmission.
      RESULTS: The readmission rate was 11.2% with a median age of 68.6 years for the
      cohort. Increased age and subsidized insurance were associated with more frequent
      admissions. For every 10-year age increase, cellulitis subjects had a 14%
      increase in readmission odds (OR 1.14, CI 1.07-1.20). Patients with subsidized
      insurance had an almost twofold increased risk (OR 1.88, CI 1.42-2.50). Smoking,
      obesity, hypertension, diabetes mellitus, renal insufficiency, tachycardia,
      hypotension, leukocytosis, and neutrophilia were not more frequent in readmitted
      patients. CONCLUSIONS: Older age and subsidized insurance were associated with
      readmission whereas severity indicators for infection including abnormal vital
      signs and laboratory markers were not significantly associated. Factors other
      than severity of infection, such as socioeconomic factors, may influence clinical
      decisions related to readmission for LLC.

PMID- 28501867
TI  - Could End-Tidal CO2 Predict Percutaneous Mitral Valve Repair?

PMID- 28501865
TI  - Fresh and Frozen-Thawed Embryo Transfer Compared to Natural Conception:
      Differences in Perinatal Outcome.
AB  - BACKGROUND/AIM: To compare the pregnancy outcome of singletons conceived after
      transfer of cryopreserved and thawed embryos (frozen embryo transfer [FET]) to
      singletons conceived after fresh embryo transfer (fresh ET) and natural conceived
      singletons. METHODS: Using a retrospective data analysis on a study population
      consisting of 1,261 singletons born after FET and 2,519 singletons born after
      fresh ET between 2006 and 2015. The control group consisted of singletons born
      after natural conception. Main outcome measures consisted of birth weight (in
      grams), gestational age, preterm birth (<37 weeks of gestation), being large for
      gestational age (LGA, above 90th weight percentile adjusted for gestational age)
      and Apgar scores. RESULTS: Babies born after FET had an increased risk of high
      birth weight (adjusted OR [AOR]) 2.92; 1.503-3.482) and being LGA (AOR fresh ET
      vs. FET 1.47; 1.210-1.787) compared to singletons born after fresh ET, as well as
      higher birth weights compared to natural conceived children. CONCLUSIONS:
      Singletons born after FET have a higher risk of high birth weight and being LGA
      compared to singletons after fresh ET and compared to natural conceived
      singletons. We assume that the freezing process might be the underlying cause.

PMID- 28501868
TI  - Factors Associated with Potassium-Competitive Acid Blocker Non-Response in
      Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease.
AB  - BACKGROUND/AIMS: Approximately 20-40% of patients with gastroesophageal reflux
      disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid
      inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P
      CAB), is significantly greater when compared to the effect of PPIs. We
      investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and
      factors associated with P-CAB non-response. METHODS: We enrolled 277 GERD
      patients receiving continuous PPI therapy. Subjects completed a self-report
      questionnaire including the frequency scale for the symptoms of GERD (FSSG).
      Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8
      weeks. After that, subjects completed the same questionnaire, and the results
      were used to identify P-CAB responders and non-responders. RESULTS: Twenty-eight
      patients were identified as P-CAB responders and 26 were non-responders.
      Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom,
      and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing
      functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR
      4.34) was associated with P-CAB non-response, whereas alcohol consumption was
      inversely associated. CONCLUSIONS: Vonoprazan treatment might be appropriate as a
      promising new strategy for PPI-refractory GERD. Co-existing FD, sleep
      disturbances, and alcohol abstinence were significantly associated with P-CAB non
      response. Other therapeutic options should be considered in patients with these
      factors.

PMID- 28501869
TI  - Intramuscular versus Vaginal Progesterone Administration in Medicated Frozen
      Embryo Transfer Cycles: A Randomized Clinical Trial Assessing Sub-Endometrial
      Contractions.
AB  - OBJECTIVE: The study aimed to assess whether sub-endometrial contractility is
      reduced by the use of intramuscular (IM) progesterone. DESIGN: This is a
      randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo
      transfer (FET) were randomly allocated to "vaginal progesterone" or "IM
      progesterone": patients randomized to the vaginal arm were treated with 200 mg
      micronized progesterone 3 times daily while patients randomized into the IM
      progesterone arm were treated with a single daily injection of 50 mg progesterone
      in oil. The main outcome measure was the number of sub-endometrial contractions
      (waves) per minute 1 day before a blastocyst embryo transfer. RESULTS: Thirty
      four patients were enrolled. The progesterone serum concentration was
      significantly higher in patients using the IM progesterone (85.2 +/- 50.1 vs.
      30.3 +/- 11.2 nmol/L, respectively) but this did not translate into a lower sub
      endometrial contractility (2.4 +/- 4.8 vs. 1.4 +/- 1.1 contraction/min,
      respectively). Clinical pregnancy rates were comparable between groups. The
      number of sub-endometrial waves was significantly lower among pregnant patients
      (p = 0.02). CONCLUSIONS: The use of IM progesterone in medicated FET cycles does
      not reduce the sub-endometrial activity compared to vaginal progesterone
      administration. Our data support a poor clinical pregnancy outcome with high wave
      activity, regardless of the progesterone mode.

PMID- 28501870
TI  - Long Non-Coding RNA XLOC_008466 Functions as an Oncogene in Human Non-Small Cell
      Lung Cancer by Targeting miR-874.
AB  - BACKGROUND: The therapy and prognosis of lung cancer are difficult because of
      multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have
      been verified as new mediators of cancer development and progression by virtue of
      their various functions. Here, we focused on the lncRNA XLOC_008466 based on
      previous microarray data. However, whether aberrant expression of XLOC_008466 in
      human non-small cell lung cancer (NSCLC) is correlated with malignancy,
      metastasis or prognosis has not been elucidated. METHODS: We performed real-time
      PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter
      assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR)
      assay to detect the function of XLOC_008466 in NSCLC. RESULTS: Up-regulation of
      XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM
      stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and
      invasion of A549 and H460 cells in vitro, but promoted cell apoptosis.
      Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA,
      directly binding to miR-874, and could affect cell proliferation, apoptosis and
      invasion through regulation of miR-874 expression as well as by increasing matrix
      metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression.
      CONCLUSIONS: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR
      874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and
      potential therapeutic target in NSCLC.

PMID- 28501871
TI  - Percutaneous Closure in Conal Septal Ventricular Septal Defects: Fact or Fiction?

PMID- 28501872
TI  - A Mechanism Study Underlying the Protective Effects of Cyclosporine-A on Lung
      Ischemia-Reperfusion Injury.
AB  - AIM: This study is aimed at validating the hypothesis that administration of
      cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R)
      injury and in exploring the underlying mechanism. METHODS: Rabbits were divided
      into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow
      cytometry was used to measure the mitochondrial membrane potential. Laser
      scanning confocal microscope was used to analyze mitochondrion permeability
      transition pore (MPTP). The apoptotic cell was detected by the TUNEL staining.
      Western blot was performed to analyze the protein expression levels. RESULTS: CsA
      not only attenuated the histopathologic alterations in lung and mitochondria
      after I/R injury, but also attenuated I/R injury through increasing MPP and
      inhibiting MPTP opening. Besides, CsA attenuated I/R injury through suppressing
      the release of cytochrome-c (CytC), inhibiting cell apoptosis and decreasing the
      expression levels of cyclophilin-D (Cyp-D), adenine nucleotide translocase 1
      (ANT1) and voltage-dependent anion channel 1 (VDAC1). Finally, we found that Cyp
      D knockdown inhibits I/R injury-induced MPTP opening and cell apoptosis.
      CONCLUSION: Our study found that the protective role of CsA on lung I/R injury
      depends on the inhibition of MPTP and CytC release, suppression of the activation
      of mitochondrial apoptosis pathway and the expressions of apoptotic-related
      proteins, as well as the decreased expression levels of ANT1 and VDAC1.

PMID- 28501873
TI  - Comparisons of Risk Factors for Intracerebral Hemorrhage versus Ischemic Stroke
      in Chinese Patients.
AB  - BACKGROUND: Chinese populations have a higher stroke incidence, a higher
      proportion of intracerebral hemorrhage (ICH), and a lower proportion of ischemic
      stroke (IS) as compared with white populations. The reasons are not fully
      understood. METHODS: To evaluate the differences of major risk factors between
      ICH and IS in Chinese stroke patients, we analysed acute ICH and IS patients
      consecutively recruited in National Taiwan University Hospital Stroke Registry
      from 2006 to 2011. We used multiple logistic regression models to examine the
      associations of risk factors with ICH vs. IS. Also, we conducted subgroup
      analyses when a strongly significant interaction was detected. RESULTS: We
      included a total of 1,373 ICH and 4,953 IS patients. ICH patients were younger
      than IS patients (mean age 61 vs. 68 years, p < 0.001), but there was no
      significant difference in gender (males 62 vs. 59%, p = 0.064). A logistic
      regression model adjusted for age, gender, and other major risk factors showed
      that both hypertension (OR 2.23, 95% CI 1.74-2.87) and alcohol intake (OR 1.44,
      95% CI 1.16-1.77) had significantly stronger associations with ICH than IS,
      whereas diabetes, atrial fibrillation, ischemic heart disease, hyperlipidemia,
      smoking, and transient ischemic attack were less associated with ICH than IS. In
      subgroup analyses, the association of hypertension with ICH vs. IS was more
      marked in younger patients. CONCLUSION: Hypertension and alcohol intake are more
      strongly associated with ICH than IS in Chinese stroke patients, especially in
      younger patients.

PMID- 28501874
TI  - Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in
      Preterm Newborns (STEP-ROP).
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a disorder of the preterm newborn
      characterized by neurovascular disruption in the immature retina that may cause
      visual impairment and blindness. OBJECTIVE: To develop a clinical screening tool
      for early postnatal prediction of ROP in preterm newborns based on risk
      information available within the first 48 h of postnatal life. METHODS: Using
      data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we
      created logistic regression models based on infants born <28 completed weeks
      gestational age. We developed a model with 60% of the data and identified birth
      weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity,
      and multiple gestation as predictors of ROP. We tested the model in the remaining
      40%, performed tenfold cross-validation, and tested the score in ELGAN study
      data. RESULTS: Of the 1,052 newborns in the VON database, 627 recorded an ROP
      status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had
      severe ROP (stages 3-5). We created a weighted score to predict any ROP based on
      the multivariable regression model. A cutoff score of 5 had the best sensitivity
      (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%,
      95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI
      69-75), but PPV was higher (80%, 95% CI 77-83). CONCLUSIONS: STEP-ROP is a
      promising screening tool. It is easy to calculate, does not rely on extensive
      postnatal data collection, and can be calculated early after birth. Early ROP
      screening may help physicians limit patient exposure to additional risk factors,
      and may be useful for risk stratification in clinical trials aimed at reducing
      ROP.

PMID- 28501875
TI  - Five-Year Neuropsychological Outcome after Stereotactic Radiofrequency
      Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy: Longitudinal Study.
AB  - PURPOSE: To assess the neuropsychological performance recoded over a period of 5
      years after stereotactic radiofrequency amygdalohippocampectomy (SAHE) in the
      treatment of mesial temporal lobe epilepsy. MATERIAL AND METHODS: Thirty patients
      (mean age 38 years, 14 females/16 males) were included in this study. Twenty-one
      patients were treated on the left side, 9 on the right. Patients underwent
      neuropsychological evaluation by the Wechsler Adult Intelligence Scale-Revised
      and the Wechsler Memory Scale-Revised preoperatively and 5 years after SAHE.
      RESULTS: Twenty-three (77%) patients were classified as Engel class I. At the
      group level, we found significant increases in all intelligence domains (Global,
      Visual, and Performance) by 19.1 (7.4), 15.8 (6.1), and 19.1 (7.9) points,
      respectively. Significant improvements were also detected in all memory measures
      (Global, Verbal, Visual, Attention/Concentration, Delayed Recall) by 19.4 (14.2),
      16.9 (13.3), 19.0 (14.7), 15.3 (15.0), and 24.6 (13.4), respectively. Patients
      with left-sided surgery improved significantly more in Attention/Concentration.
      Otherwise, there were no statistically significant differences in memory function
      improvements between subgroups according to the operated side. CONCLUSION: After
      SAHE, we found favorable long-term neuropsychological outcomes. These results
      could be caused by incomplete destruction of target structures and minimization
      of collateral damage that possibly enables adaptive postoperative neuronal
      reorganization.

PMID- 28501876
TI  - Stereotactic Radiosurgery as Initial Surgical Management for Elderly Patients
      with Trigeminal Neuralgia.
AB  - BACKGROUND: Management of older patients with medically refractory trigeminal
      neuralgia (TN) is yet a matter of debate. OBJECTIVE: We sought to determine the
      benefit of stereotactic radiosurgery (SRS) as the sole surgical management in
      older patients (>=70 years). METHODS: One hundred and twenty-seven patients (>=70
      years) with typical TN underwent SRS as initial surgical management. The median
      maximum dose for the first procedure was 80 Gy. Repeat SRS was performed in 46
      patients who developed recurrent pain. RESULTS: After the first SRS, the initial
      pain control was achieved in 91% of patients. Complete pain relief (Barrow
      Neurological Institute [BNI] score I) developed in 75 patients (59%) and was
      maintained in 59, 39, and 22% of patients at 1, 3, and 5 years. Following repeat
      SRS, the rate of complete pain relief was 79, 55, and 41% at 1, 3, and 5 years.
      The chance of BNI I preservation was greater after repeat SRS compared to initial
      SRS (hazards ratio: 2.02, p < 0.0001). The incidence of trigeminal sensory loss
      was 17% after initial SRS but increased to 39% after repeat SRS. CONCLUSIONS: SRS
      alone was used effectively in older TN patients to achieve pain control.
      Recurrent pain responded to retreatment but was associated with an increased risk
      of sensory dysfunction.

PMID- 28501877
TI  - Association Between Sex and Speech Auditory Brainstem Responses in Adults, and
      Relationship to Sex Hormone Levels.
AB  - BACKGROUND The aim of this study was to investigate the association between sex
      and speech-ABR in adults, and its relationship to sex hormone levels. MATERIAL
      AND METHODS Speech-ABR were elicited with the consonant-vowel syllable (/da/) in
      a total of 35 adults. Reproductive hormone levels were also measured. RESULTS The
      transient response of the speech-ABR (waves V, A, and O) in females show a
      shorter latency (waves V, A and O) and a larger amplitude (waves V and A) than in
      males (P<0.05), except for the amplitude of peak O (P>0.05). The sustained
      response of females exhibited a larger amplitude (wave F, P<0.05) and a shorter
      latency (wave D, E, and F, P<0.05) than in males, except for the amplitude of
      peak D and E (P>0.05). The latencies of speech-ABR were positively correlated
      with testosterone level (P<0.05), and were negatively correlated with estradiol
      (E2) levels (P<0.05), except for wave E (P>0.05). The E2 showed a positive
      correlation with the absolute value of amplitude of the speech-ABR (P < 0.05). On
      the contrary, total testosterone showed a negative correlation with the absolute
      value of amplitude the speech-ABR (P<0.05), except for wave D and wave O
      (P>0.05). CONCLUSIONS Sex differences in speech-ABR are significant in adults.
      The latencies and amplitude of the speech-ABR waves were correlated with the E2
      concentration and testosterone level. The sex hormones likely affect speech
      encoding in the brainstem.

PMID- 28501878
TI  - [Oral manifestations of ulcerative colitis].
AB  - Ulcerative colitis is an inflammatory bowel disease occurring relatively
      frequently in industrialised regions of the world. Pyostomatitis vegetans is the
      most characteristic pathognomonic oral manifestation but other oral abnormalities
      like aphthous lesions, caries and periodontitis are more prevalent in patients
      with ulcerative colitis. Oral care providers must be aware of these problems if
      they are to provide adequate oral care.

PMID- 28501879
TI  - [Implant-supported 3D-printed bridge in the edentulous maxilla].
AB  - A healthy 72-year-old man presented with retention problems concerning the
      dentures in his maxilla. On account of extreme resorption, placement of implants
      without prior bone augmentation was not an option. The proposal was to use
      autologous bone harvested from the iliac crest. After a healing period of 4
      months, a cone beam computed tomography scan was made, following which the
      virtual implant planning of 6 implants was carried out. With the help of a
      template supported by osteosynthesis screws, which had already been inserted
      during the augmentation procedure, the plan was applied to the patient. The
      precision of the fit between the planning and the actual placement of the
      implants has become so high that it was decided to place a 3D-printed dental
      bridge immediately following implant placement. The treatment trajectory and the
      costs can thus be significantly reduced whilst the patient gets to enjoy the
      implant-supported dentures sooner.

PMID- 28501880
TI  - [Preventive dentistry 5. Secondary caries].
AB  - Secondary caries is reported as one of the most important reasons for replacing
      restorations. The patient's general caries risk plays an important role in the
      development of secondary caries. The connection, at the patient level, between
      various factors, the risk of caries and restoration factors, such as the presence
      of a gap and the kind of restoration material, deserves additional investigation.
      The minimum gap width in which secondary caries can develop is most likely less
      than 100 um and could depend on the patient's caries risk. Composite restorations
      seem more susceptible to secondary caries than amalgam restorations in patients
      with high caries risk. So far, there is no unambiguous explanation for this
      difference. The prevention of secondary caries is comparable to that of primary
      caries and stresses the importance of fluoride, diet and oral hygiene.

PMID- 28501881
TI  - [Medicaments and oral healthcare 4. Pharmacotherapy in (frail and care dependent)
      older people].
AB  - Polypharmacy is the consequence of multimorbidity. Both phenomena may cause
      functional limitations and/or frailty and/or care dependency in older people. In
      the human body, a medicament undergoes at least 3 important actions: absorption,
      distribution and elimination. These actions may proceed aberrantly in older
      people. Following interaction with receptors, a medicament triggers a chain
      reaction in the human body. The receptors and each link of the chain reaction may
      be subject to changes due to diseases as well as ageing. This, particularly, is
      the case with regard to medications directed towards the central nervous system
      and the cardiovascular system. Furthermore, interactions may occur between
      various medications mutually and between medications on the one hand and on the
      other hand food and water intake, self-medication with herbs, and diseases.
      Moreover, older people usually experience more adverse effects of medications
      when compared to younger people. This is due to altered body actions and
      reactions, polypharmacy and the many possible interactions. In older people,
      utilisation and intake of medications often give rise to problems that can be
      divided into medicament-related, patient-related, care- and care provider-related
      and other problems.

PMID- 28501882
TI  - [Caries in deprived areas 2. Youngsters].
AB  - In the Netherlands, no epidemiologic data on the oral health of cultural groups
      of children and adolescents living in deprived areas are available. The aim of
      the present study was to obtain an impression of the amount of caries experience
      among poorly educated groups of youngsters in deprived areas, in comparison with
      a reference group of poorly educated youngsters from the cities of Alphen aan den
      Rijn, Gouda, 's-Hertogenbosch and Breda. 725 Poorly educated respondents
      participated in a clinical and sociological study. The reference group had the
      lowest caries experience and the youngsters living in deprived areas with a non
      Dutch cultural affiliation had the largest amount of caries experience. The
      latter group had more untreated caries and in 20-year-olds, a relatively large
      number of teeth had been extracted. Despite the low numbers, the difference in
      average DMFS scores among 14- and 20-year-olds were statistically significant. In
      the Netherlands a cultural dichotomy in oral health appears to exist, independent
      of level of education, in which youngsters with a non-Dutch cultural background
      are at a disadvantage.

PMID- 28501883
TI  - [A PhD completed 9. The value of oral foci screening in oncology patients].
AB  - In both patients who undergo radiotherapy because of a tumour in the head and
      neck region and patients who are treated with high doses of chemotherapy because
      of haematological disorders, prior to treatment an oral foci screening is carried
      out. The aim of this focus investigation is to identify oral abnormalities, the
      so-called oral foci. Such foci can lead to oral problems during or post
      treatment. A careful oral foci screening, conforming to protocol, appears to be
      very relevant for patients who have to undergo head and neck radiotherapy.
      Particular attention must be devoted to the evaluation of the perodontium,
      because the chance of disorders affecting the bone-healing that appear post
      radiotherapy in the head and neck region is increased in patients with
      periodontitis. In patients with a haematological disorder, asymptomatic, chronic
      foci do not require treatment prior to or during the oncological treatment
      because such oral foci do not increase an extra risk of infectious complications,
      despite what was hitherto believed.

PMID- 28501884
TI  - The effect of systemic treatments on periostin expression reflects their
      interference with the eosinophilic inflammation in chronic rhinosinusitis with
      nasal polyps.
AB  - BACKGROUND: Periostin is a recently discovered biomarker for eosinophilic
      inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed
      chronic inflammatory airway disease. Medical treatments aim to relieve symptoms
      and maintain clinical control by interfering with the inflammatory cascade. The
      effect on nasal and serum periostin levels is however yet unknown. We aimed to
      evaluate the effect of omalizumab, mepolizumab, methylprednisolone and
      doxycycline on nasal and systemic periostin expression. METHODS: This study is
      based on 3 previously published trials. Nasal and systemic periostin were
      assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14),
      methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15). There was a
      control group for each treatment scheme. Doxycycline (200 mg on the first day,
      followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were
      administered during 20 days; mepolizumab was injected at baseline and at 4 weeks.
      Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet.
      RESULTS: Methylprednisolone and omalizumab significantly reduced serum periostin
      levels at 4 and 8 weeks, respectively, after the start of the treatment. The
      effect of methylprednisolone was transient. Nasal periostin levels decreased
      significantly after 8 weeks of treatment with mepolizumab. The periostin
      expression is in accordance with the previously reported effect on the
      eosinophilic inflammation and clinical outcome. CONCLUSION: All treatment options
      distinctly influence periostin expression, reflecting the interference with the
      local or systemic eosinophilic inflammatory cascade.

PMID- 28501886
TI  - Rhinophototherapy in chronic rhinosinusitis: a double blind randomized placebo
      controlled trial.
AB  - BACKGROUND: This study evaluated the efficacy of rhinophototherapy in patients
      with chronic rhinosinusitis (CRS) without nasal polyps. METHOD: In this
      randomized double-blind, placebo-controlled trial, CRS patients (n=50) received
      either mixed visible and ultraviolet (UVA and UVB) light source application
      (mUV/VIS) or visible light alone that served as placebo. Both groups were treated
      for 3 weeks. RESULTS: Results in the rhinophototherapy and placebo group were not
      significantly different and failed to reduce patient-reported outcomes measures
      (Rhinosinusits Disability Index, Visual Analogic Scale of symptom severity) and
      objective scores (rhinomanometry, olfactory thresholds, nasal Nitic Oxide
      concentrations), immediately and one month after treatment. CONCLUSIONS: The
      present data suggest that rhinophototherapy is not an efficient treatment for
      chronic rhinosinusitis without nasal polyps.

PMID- 28501885
TI  - EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on
      needs and priorities in rhinitis and rhinosinusitis.
AB  - The first European Rhinology Research Forum organized by the European Forum for
      Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the
      Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in
      collaboration with the European Rhinologic Society (ERS) and the Global Allergy
      and Asthma European Network (GA2LEN). One hundred and thirty participants
      (medical doctors from different specialties, researchers, as well as patients and
      industry representatives) from 27 countries took part in the multiple perspective
      discussions including brainstorming sessions on care pathways and research needs
      in rhinitis and rhinosinusitis. The debates started with an overview of the
      current state of the art, including weaknesses and strengths of the current
      practices, followed by the identification of essential research needs, thoroughly
      integrated in the context of Precision Medicine (PM), with personalized care,
      prediction of success of treatment, participation of the patient and prevention
      of disease as key principles for improving current clinical practices. This
      report provides a concise summary of the outcomes of the brainstorming sessions
      of the European Rhinology Research Forum 2016.

PMID- 28501891
TI  - Dual-energy X-ray absorptiometry and fracture prediction in patients with spinal
      cord injuries and disorders: methodological issues.

PMID- 28501890
TI  - The role of adipokines as prognostic factors of one-year mortality in hip
      fracture patients.
AB  - : This study investigated the impact of anthropometric parameters, adiponectin,
      leptin, homeostatic model assessment for insulin resistance (HOMA-IR), beta
      isomerised C-terminal telopeptide of collagen type I (beta-CTX), and routine
      biochemical tests on one-year mortality in hip fracture patients. We found that
      male patients with high adiponectin, leptin, and beta-CTX levels had a 5-fold
      increase in all-cause one-year mortality. INTRODUCTION: Several predictors of one
      year hip fracture mortality have been identified including advanced age, male
      sex, low bone mineral density, and preexisting comorbidities. However, the impact
      of metabolic parameters on hip fracture mortality remains unknown. The aim of
      this study was to examine the effect of serum leptin and adiponectin levels, as
      well as other metabolic parameters on all-cause one-year hip fracture mortality.
      METHODS: This prospective study included 236 patients of all ages with non
      traumatic hip fractures. Anthropometric parameters, adiponectin, leptin, HOMA-IR,
      beta-CTX, and routine biochemical tests were recorded at admission and correlated
      with one-year mortality by using multivariate Cox proportional hazard models.
      RESULTS: The median patient age was 82 (75-87) years, and one-year mortality rate
      was 28.4%. In univariate analysis, adiponectin, age, beta-CTX, and renal function
      were associated with mortality. However, in a multivariate model, male gender,
      high beta-CTX, adiponectin, and leptin were independently associated with
      increased mortality. Thus, we constructed a nomogram that included all the latter
      variables in addition to age. The nomogram predicted mortality with a sensitivity
      of 74.8% (66.0-82.3) and specificity of 74.4% (57.9-87.0), and had an area under
      the curve of 0.784. Patients that scored <9.2 had a mortality of 10.1%, while
      those with >9.2 had a mortality of 49.2% (relative risk 5.4, 95% CI 2.8-10.2, P <
      0.001). CONCLUSION: Male patients with high adiponectin, leptin, and beta-CTX
      levels have a 5-fold increase in all-cause one-year mortality after hip fracture.

PMID- 28501892
TI  - A New Primer to Amplify pmoA Gene From NC10 Bacteria in the Sediments of
      Dongchang Lake and Dongping Lake.
AB  - Nitrite-dependent anaerobic methane oxidation (n-damo) is catalyzed by the NC10
      phylum bacterium "Candidatus Methylomirabilis oxyfera" (M. oxyfera). Generally,
      the pmoA gene is applied as a functional marker to test and identify NC10-like
      bacteria. However, it is difficult to detect the NC10 bacteria from sediments of
      freshwater lake (Dongchang Lake and Dongping Lake) with the previous pmoA gene
      primer sets. In this work, a new primer cmo208 was designed and used to amplify
      pmoA gene of NC10-like bacteria. A newly nested PCR approach was performed using
      the new primer cmo208 and the previous primers cmo182, cmo682, and cmo568 to
      detect the NC10 bacteria. The obtained pmoA gene sequences exhibited 85-92%
      nucleotide identity and 95-97% amino acid sequence identity to pmoA gene of M.
      oxyfera. The obtained diversity of pmoA gene sequences coincided well with the
      diversity of 16S rRNA sequences. These results indicated that the newly designed
      pmoA primer cmo208 could give one more option to detect NC10 bacteria from
      different environmental samples.

PMID- 28501893
TI  - HSPB8 haploinsufficiency causes dominant adult-onset axial and distal myopathy.

PMID- 28501895
TI  - Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to
      acute hypoxia.
AB  - Brain hypoxia is involved in many diseases. The activation of angiogenesis is one
      of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In
      a previous work, we have shown that the adult rat striatum promotes angiogenesis
      in response to hypoxia via upregulation of the most important proangiogenic
      factor, the vascular endothelial growth factor (VEGF). However, the effects of
      hypoxia on angiogenesis in the aged striatum remain unknown and constitute our
      aim. Here we show the upregulation of hypoxia-inducible factor-1alpha in the
      striatum of aged (24-25 months old) Wistar rats exposed to acute hypoxia and
      analysed during a reoxygenation period ranging from 0 h to 5 days. While the mRNA
      expression of the proangiogenic factors VEGF, transforming growth factor-beta1
      (TGF-beta1), and adrenomedullin dropped at 0 h post-hypoxia compared to normoxic
      control, no changes were detected at the protein level, showing an impaired
      response of these proangiogenic factors to hypoxia in the aged striatum. However,
      the striatal blood vessel network increased at 24 h of reoxygenation, suggesting
      that mechanisms independent from these proangiogenic factors may be involved in
      hypoxia-induced angiogenesis in the striatum of aged rats. A thorough
      understanding of the factors involved in the response to hypoxia is essential to
      guide the design of therapies for hypoxia-related diseases in the aged brain.

PMID- 28501894
TI  - Influence of ageing on the microarchitecture of the spleen and lymph nodes.
AB  - The elderly have a decreased response to vaccination and an increased
      susceptibility to infectious diseases. The spleen and lymph nodes are important
      secondary lymphoid organs where immune cells can rapidly respond to pathogenic
      material in the blood and lymph in order to mount long-term adaptive immune
      responses to those pathogens. In aged mice and humans structural changes occur to
      both the spleen and lymph nodes. These structural changes affect the functioning
      of the immune cells within, which may ultimate result in less effective or
      decreased immune responses. This review describes our current understanding of
      the structural changes that occur to the spleen and lymph nodes of elderly mice.
      However, where data are available, we also discuss whether similar changes occur
      in tissues from elderly humans. A particular focus is made on how these
      structural changes are considered to impact on the functioning of the immune
      cells within. The world's population is currently living longer than ever before.
      The increased incidence and severity of infectious diseases in the elderly has
      the potential to have a significant impact on the health care system if solutions
      are not identified. A thorough understanding of the molecular causes of these
      ageing-related structural changes to the spleen and lymph nodes may help to
      identify novel treatments that could repair them, and in doing so, improve immune
      responses and vaccine efficacy in the elderly.

PMID- 28501896
TI  - What do Biologists Make of the Species Problem?
AB  - The concept of species is one of the core concepts in biology and one of the
      cornerstones of evolutionary biology, yet it is rife with conceptual problems.
      Philosophers of biology have been discussing the concept of species for decades,
      and in doing so they sometimes appeal to the views of biologists. However, their
      statements as to what biologists think are seldom supported by empirical data. In
      order to investigate what biologists actually think about the key issues related
      to the problem of species, we have conducted a survey on the sample of 193
      biologists from the population of biologists from over 150 biology departments at
      universities in the US and the EU. This article presents and discusses the
      results of the survey. Some results confirm and others falsify the reiterated
      statements of philosophers of biology as to what biologists think, but all
      results we obtained should be informative and relevant for future discussions of
      the problem of species.

PMID- 28501897
TI  - MiR-181b modulates chemosensitivity of glioblastoma multiforme cells to
      temozolomide by targeting the epidermal growth factor receptor.
AB  - Temozolomide (TMZ) is a promising chemotherapeutic agent to treat Glioblastoma
      multiforme (GBM). However, resistance to TMZ develops quickly with a high
      frequency. The mechanisms underlying GBM cells' resistance to TMZ are not fully
      understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate
      protein expression by cleaving or repressing the translation of target mRNAs.
      Recently, miRNAs have been discovered to play important roles in drug resistance.
      A previous study showed that miR-181b in involved in glioma tumorigenesis. Thus,
      it would be valuable to explore the functions and mechanisms of miR-181b in
      regulating GMB cells' sensitivity to TMZ. In this study, quantitative real-time
      reverse transcription PCR (qRT-PCR) data indicated that miR-181b was
      significantly downregulated in recurrent GBM tissues compared with initial GBM
      tissues. We also found that miR-181b overexpression increased the chemo
      sensitivity of GBM cells to TMZ and potentiated TMZ-induced apoptosis in vitro
      and in vivo. Moreover, we demonstrated that the epidermal growth factor receptor
      (EGFR) was a direct target of miR-181b: restoration of EGFR rescued the
      inhibitory effects of miR-181b and TMZ treatment. Taken together, our data
      support strongly an important role for miR-181b in conferring TMZ resistance by
      targeting EGFR expression.

PMID- 28501898
TI  - Family First? The Costs and Benefits of Family Centrality for Adolescents with
      High-Conflict Families.
AB  - Youth who do not identify with or value their families (i.e., low family
      centrality) are considered to be at risk for maladjustment. However, the current
      study investigated whether low family centrality may be adaptive in negative
      family contexts (i.e., high family conflict) because youth's self-worth should be
      less tied to the quality of their family relationships. Multilevel models using
      daily diaries and latent variable interactions using longitudinal questionnaires
      indicated that, among a sample of 428 Mexican American adolescents (49.8% male, M
      age = 15.02 years), lower family centrality was generally detrimental to youth's
      well-being. However, for youth in adverse family environments, low family
      centrality ceased to function as a risk factor. The present findings suggest that
      family centrality values play a more nuanced role in youth well-being than
      previously believed, such that low family centrality may be an adaptive response
      to significant family challenges.

PMID- 28501899
TI  - Is there a "July effect" in pediatric neurosurgery?
AB  - PURPOSE: The belief that July, when resident physicians' training year begins,
      may be associated with increased risk of patient morbidity and mortality is known
      as the "July effect." This study aimed to compare complication rates after
      pediatric neurosurgical procedures in the first versus last academic quarters in
      two national datasets. METHODS: Data were extracted from the National Surgical
      Quality Improvement Program-Pediatrics (NSQIP-P) database for year 2012 for 30
      day complication events and the Kids' Inpatient Database (KID) for year 2012 for
      in-hospital complication events after pediatric neurosurgical procedures.
      Descriptive and analytic statistical methods were used to characterize the impact
      of seasonal variation between the first and last quarters on complications.
      RESULTS: Three thousand six hundred twenty-four procedures in the NSQIP-P dataset
      and 14,855 hospitalizations in KID were included in the study cohort. No
      significant difference was observed between the first and fourth quarters for
      these complication events: wound disruption/dehiscence, wound infection, nerve
      injury, bleeding requiring transfusion, central line-associated BSI, deep venous
      thrombosis/pulmonary embolism, urinary tract infection, renal failure, re
      intubation/pulmonary failure, cardiac arrest, stroke, coma, and death. There was
      no difference in the average length of stay or average length of surgical time.
      In the NSQIP-P, the first quarter was associated with a significantly increased
      incidence of pneumonia and unplanned re-operation; there was a trend towards
      increased incidence of unplanned re-admission and sepsis. In KID, there was no
      difference in the rate of pneumonia or sepsis. CONCLUSION: For the majority of
      morbidity and mortality events, no significant difference was found in occurrence
      rates between the first and last quarters.

PMID- 28501900
TI  - Autonomic nervous system in newborns: a review based on heart rate variability.
AB  - PURPOSE: Heart rate variability (HRV) has been a relevant tool in the assessment
      of the autonomic nervous system (ANS). How autonomic control normally develops in
      newborns and how it is affected by gestational age (GA) is not fully understood.
      We aimed to review the current evidence on HRV in preterm (PT) and term neonates
      (TN) and investigate the relation between GA and the maturation of ANS. METHODS:
      Electronic databases (Pubmed, World of Science, and Scopus) were searched for
      studies from 1997 to 2017 examining HRV (time and frequency domain) in PT and TN
      who followed to the Task Force (1996) guidelines. Ten studies met our inclusion
      criteria and were analyzed. RESULTS: An increasing postnatal age was related to a
      significant rise of HRV parameters. Several significant differences were
      established between PT and TN (lower values on PTN), also found when PTN are
      evaluated at their theoretical term age. In general, there were no relevant
      results on LF/HF (low frequency/high frequency) ratio, as being an adequate
      marker of sympathovagal balance, but this was not a universal finding of this
      review. Frequency parameters that were more often used to evaluate newborns and
      HF showed the most relevant increase with GA. CONCLUSIONS: HRV is an important
      tool to assess the maturation of ANS in newborns and there is a progressive
      increasing on cardiac parasympathetic activity, according to GA. HF appears as a
      relevant parameter in measurements of vagal maturation. HRV is higher in TN when
      compared with PTN and is more studied in newborns in terms of frequency domain.
      Standard recommendations in newborns remain to be fully defined.

PMID- 28501901
TI  - Production of Mycosporine-Like Amino Acids from Gracilaria vermiculophylla
      (Rhodophyta) Cultured Through One Year in an Integrated Multi-trophic Aquaculture
      (IMTA) System.
AB  - This study evaluates the production of biomass and mycosporine-like amino acids
      (MAAs) throughout the year in Gracilaria vermiculophylla (Rhodophyta) collected
      in Ria de Aveiro (Portugal). The algae were grown in outdoor tanks in seawater
      with the addition of fishpond effluents under two different water flows (100 and
      200 L h-1) in an integrated multi-trophic aquaculture (IMTA) system (tanks 1200
      L; 1.5 m2) and different algal densities (3, 5, and 7 kg m-2). MAA content in
      IMTA seaweeds was significantly affected by the interaction of time and stocking
      density, but not by the water flow. The highest MAA content was observed in April
      (about 3.13 mg g-1 DW) followed by May (1.79 mg g-1 DW). Seaweed biomass
      productivity was higher in May (372.06 g DW m-2 week-1) than in April (353.40 g
      DW m-2 week-1). Four MAAs were identified by HPLC and electrospray ionization
      mass spectrometry (ESI-MS) in G. vermiculophylla: Porphyra-334, Shinorine,
      Palythine and Asterina-330. The highest levels of Porphyra-334 and Shinorine were
      reached from November to January and the Palythine + Asterina-330 from April to
      August. Taking into account the average biomass and MAA production of G.
      vermiculophylla growing in this IMTA system (8.56 g of MAA in 18 m2 culture along
      8 months; 35.5% produced in April), a total amount of 71.33 g MAA year-1 could be
      produced in this system by scaling up to 100 m2. MAAs could be further used as
      photoprotector and antioxidant compounds in cosmetic products.

PMID- 28501902
TI  - A new 4-Amino-7-Nitro-2,1,3-Benzoxadiazole (ANBD)-Based Fluorescent Probe for the
      Detection of Hg2.
AB  - Based on the photoinduced electron transfer (PET) principle, 4-amino-7-nitro
      2,1,3-benzoxadiazole (ANBD) has been used as a fluorophore to develop a new
      fluorescent probe, 4-(2-N,N-dimethylthioacetamide)amino-7-nitro-2,1,3
      benzoxadiazole (2), for the detection of Hg2+. Upon the addition of Hg2+, a 46
      fold fluorescence enhancement occurs. Moreover the probe 2 exhibits a high
      selectivity and sensitivity to Hg2+, even in the presence of other common metal
      ions. Under optimal reaction conditions, a good linearity can be obtained in the
      range of 0.5-2.5 MUM, and the detection limit is 0.05 MUM. In addition, the
      desulfurization reaction mechanism is proposed based on electrospray ionization
      mass spectrum. The present study is not only a supplement to the detection method
      of Hg2+, but also a merit to the development of ANBD-based fluorescent probes.

PMID- 28501903
TI  - Coumarin-Pyrazole Hybrid with Red Shifted ESIPT Emission and AIE Characteristics 
      a Comprehensive Study.
AB  - The newly synthesized three coumarin pyrazole hybrid excited state intramolecular
      proton transfer (ESIPT) dyes show efficient charge transfer from the pyrazole
      ring and the coumarin towards the electron withdrawing dicyanovinylene group as
      revealed from the frontier molecular orbitals. Aggregation induced emission
      enhancement (AIEE) studies with 2-((3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1-phenyl
      1H-pyrazol-4-yl)methylene) malononitrile showed 9 fold increase in the emission
      enhancement in 90% DMF-H2O mixture. Lippert-Mataga theory explained the
      solvatochromic behavior of the dyes in various solvents. The charge transfer
      characteristics and non-linear optical (NLO) properties have been supported and
      correlated with bond length alternation, bond order alternation and vibrational
      spectrum. As values of bond order alternation (BOA) tend to be more towards
      negative and as the value of alpha increases beta decreases while the values of
      gamma depends on the values of alpha and beta. The observed values of gamma are
      positive which revealed that beta contributes significantly. The dyes exhibit
      linear and NLO properties superior to urea. (E)-2-(3-(2-(3-(4-Hydroxy-2-oxo-2H
      chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)vinyl)-5,5-dimethylcyclohex-2-en-1
      ylidene) malononitrile shows enhanced linear and non-linear properties among the
      three dyes.

PMID- 28501904
TI  - Relationship Between Perisylvian Essential Language Sites and Arcuate Fasciculus
      in the Left Hemisphere of Healthy Adults.
AB  - Essential language sites and the arcuate fasciculus (AF) have been extensively
      researched. However, the relationship between them remains insufficiently
      studied, especially in healthy people. Navigated transcranial magnetic
      stimulation (nTMS) is increasingly used in language mapping. While enjoying the
      advantage of non-invasiveness, it is also capable of inducing a virtual lesion in
      the brain. Thus, it offers the possibility of using the virtual-lesion method to
      study the healthy brain. This study combined nTMS and diffusion tensor imaging
      (DTI) tractography to investigate the relationship between essential language
      sites and the AF in 30 healthy right-handed volunteers. A total of 143 essential
      language sites were identified using nTMS, and a total of 175 AF terminations
      were identified using DTI tractography. Sixty-six sites had a direct correlation
      with the AF, accounting for 46% of the total essential language sites. Forty
      seven AF terminations harbored essential language sites, accounting for 27% of
      the total AF terminations. Upon data rendering to the cortical parcellation
      system, a region-related heterogeneity of the correlation rate was found. This
      study provides the first data on the relationship between essential language
      sites and the AF in healthy adults.

PMID- 28501905
TI  - Investigation of Pain Mechanisms by Calcium Imaging Approaches.
AB  - Due to the complex circuitry and plethora of cell types involved in
      somatosensation, it is becoming increasingly important to be able to observe
      cellular activity at the population level. In addition, since cells rely on an
      intricate variety of extracellular factors, it is important to strive to maintain
      the physiological environment. Many electrophysiological techniques require the
      implementation of artificially-produced physiological environments and it can be
      difficult to assess the activity of many cells simultaneously. Moreover, imaging
      Ca2+ transients using Ca2+-sensitive dyes often requires in vitro preparations or
      in vivo injections, which can lead to variable expression levels. With the
      development of more sensitive genetically-encoded Ca2+ indicators (GECIs) it is
      now possible to observe changes in Ca2+ transients in large populations of cells
      at the same time. Recently, groups have used a GECI called GCaMP to address
      fundamental questions in somatosensation. Researchers can now induce GCaMP
      expression in the mouse genome using viral or gene knock-in approaches and
      observe the activity of populations of cells in the pain pathway such as dorsal
      root ganglia (DRG), spinal neurons, or glia. This approach can be used in vivo
      and thus maintains the organism's biological integrity. The implementation of
      GCaMP imaging has led to many advances in our understanding of somatosensation.
      Here, we review the current findings in pain research using GCaMP imaging as well
      as discussing potential methodological considerations.

PMID- 28501907
TI  - Tacit knowledge.
AB  - Information that is not made explicit is nonetheless embedded in most of our
      standard procedures. In its simplest form, embedded information may take the form
      of prior knowledge held by the researcher and presumed to be agreed to by
      consumers of the research product. More interesting are the settings in which the
      prior information is held unconsciously by both researcher and reader, or when
      the very form of an "effective procedure" incorporates its creator's (unspoken)
      understanding of a problem. While it may not be productive to exhaustively detail
      the embedded or tacit knowledge that manifests itself in creative scientific
      work, at least at the beginning, we may want to routinize methods for extracting
      and documenting the ways of thinking that make "experts" expert. We should not
      back away from both expecting and respecting the tacit knowledge the pervades our
      work and the work of others.

PMID- 28501906
TI  - Medication use for the treatment of diabetes in obese individuals.
AB  - Obesity is a major cause of type 2 diabetes and may complicate type 1 diabetes.
      Weight loss for obese individuals with diabetes has many health benefits, often
      leads to improvement in glucose control and sometimes, in type 2 diabetes, near
      normalisation of abnormal glucose metabolism. Weight loss is difficult to
      maintain and attempts to lose weight may be undermined by some diabetes
      treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst
      lifestyle support should be the primary approach to aid individuals who wish to
      lose weight, pharmacological approaches can also be considered. These include
      choosing glucose-lowering drugs or drug combinations that are weight neutral or
      result in weight loss or prescribing drugs that are specifically approved as anti
      obesity medication. Given that some of the newer glucose-lowering medications
      that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1
      RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are also being used
      or considered for use as anti-obesity drugs, it seems that the distinction
      between glucose-lowering medication and weight loss medication is becoming
      blurred. This review discusses the main pharmacological approaches that can be
      used to support weight loss in individuals with diabetes.

PMID- 28501908
TI  - A tale of three cuffs: the hemodynamics of blood flow restriction.
AB  - INTRODUCTION: The blood flow response to relative levels of blood flow
      restriction (BFR) across varying cuff widths is not well documented. With the
      variety of cuff widths and pressures reported in the literature, the effects of
      different cuffs and pressures on blood flow require investigation. PURPOSE: To
      measure blood pressure using three commonly used BFR cuffs, examine possible
      venous/arterial restriction pressures, and measure hemodynamic responses to
      relative levels of BFR using these same cuffs. METHODS: 43 participants
      (Experiment 1, brachial artery blood pressure assessed) and 38 participants
      (Experiment 2, brachial artery blood flow assessed using ultrasound, cuff placed
      at proximal portion of arm) volunteered for this study. RESULTS: Blood pressure
      measurement was higher in the 5 cm cuff than in the 10 and 12 cm cuffs. Sub
      diastolic relative pressures appear to occur predominantly at <60% of arterial
      occlusion pressure (AOP). Blood flow under relative levels of restriction
      decreases in a non-linear fashion, with minimal differences between cuffs
      [resting: 50.3 (44.2) ml min-1; 10% AOP: 42.0 (36.8); 20%: 33.6 (28.6); 30%: 23.6
      (20.4); 40%: 17.1 (15.9); 50%: 12.5 (9.4); 60%: 11.5 (8.1); 70%: 11.4 (7.0); 80%:
      10.3 (6.3); 90%: 7.9 (4.8); 100%: 1.5 (2.9)]. Peak blood velocity remains
      relatively constant until higher levels (>70% of AOP) are surpassed. Calculated
      mean shear rate decreases in a similar fashion as blood flow. CONCLUSIONS: Under
      relative levels of restriction, pressures from 40 to 90% of AOP appear to
      decrease blood flow to a similar degree in these three cuffs. Relative pressures
      appear to elicit a similar blood flow stimulus when accounting for cuff width and
      participant characteristics.

PMID- 28501909
TI  - Vitamin K antagonist therapy: changes in the treated populations and in
      management results in Italian anticoagulation clinics compared with those
      recorded 20 years ago.
AB  - Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world.
      An appropriate management of treated patients is crucial for their efficacy and
      safety. The prospective, observational, multicenter, inception-cohort FCSA-START
      Register, a branch of START Register (NCT02219984) included VKA-treated patients
      managed by centers of Italian Federation of anticoagulation clinics (AC).
      Baseline patient characteristics and data during treatment were analyzed and
      compared with those of ISCOAT study, performed by the Federation and published in
      1996/7. 5707 naive patients [53% males, mean age 73.0 years (28.1% >80 years)],
      61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism
      were included. During the 8906 patient-years (pt-yrs) of observation, 123
      patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non
      major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more
      frequent in elderly (>=70 years; p = 0.04), and during initial 3-month therapy (p
      = 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results <3.0,
      increasing to 12.5% for INR >= 4.5. Thrombotic events were 47 (0.53% pt-yrs; 4
      fatal 0.04% pt-yrs). Compared with ISCOAT-1996/7 results, patients older than 80
      y are increased from 8 to 28% (p < 0.01), and those treated for AF are increased
      from 17 to 61%. The quality of anticoagulation control and incidence of MB are
      not different. However, thrombotic complications fell drastically from 3.5 to
      0.53% pt-yrs (p < 0.01), with lower mortality (p = 0.01). VKA-treated patients
      monitored in Italian AC have good clinical results, with low bleeding and
      thrombotic complications rates. Important changes in the treated population and
      improvement in thrombotic complications are detected compared with the ISCOAT
      1996/7 study.

PMID- 28501911
TI  - Analysis of circumflex artery anatomy by real time 3D transesophageal
      echocardiography compared to cardiac computed tomography.
AB  - Iatrogenic injury to the circumflex artery (Cx) due to its close proximity to the
      mitral annulus is a rare but dreadful complication that can occur during mitral
      valve repair. The aim of our study was to compare multiple measurements of the Cx
      datasets, obtained by real time three-dimensional transesophageal
      echocardiography (RT3D TEE) and corresponding measurements assessed in multi
      planar three-dimensional images acquired by multidetector computed tomography
      (MDCT). Preoperative RT3D TEE and MDCT datasets of 25 patients who had previously
      undergone minimally invasive mitral valve surgery were retrospectively analyzed.
      The vessel diameter and the horizontal as well as vertical distances from the
      center of the Cx to the mitral valve annulus were measured. Horizontal as well as
      vertical Cx distances showed a strong correlation between measurements of RT3D
      TEE and MDCT whereas the measurements of the Cx diameter showed no correlation.
      Measurements of horizontal and vertical distances of the Cx to the mitral annulus
      can be performed using RT3D TEE and show good correlation with MDCT-based
      measurements.

PMID- 28501913
TI  - Chronic Myeloid Leukemia: Immunobiology and Novel Immunotherapeutic Approaches.
AB  - Imatinib has revolutionized the treatment and prognosis of chronic myeloid
      leukemia (CML) with survival rates now approaching those of the age-matched
      healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI)
      treatment, it is necessary to develop complementary therapies to target minimal
      residual disease. Recent findings by a number of investigators in both CML mouse
      models and CML patients offer evidence that many factors in the leukemic
      microenvironment can collectively contribute to immune escape, including
      expansion of myeloid-derived suppressor cells, programmed death-1/programmed
      death-1 ligand interactions resulting in T-cell impairment, expression of soluble
      suppressive factors such as soluble CD25, and down-regulation of MHC molecules by
      CML cells. Other investigators have studied the role of cytokines on the
      resistance to TKIs by leukemic stem cells (LSCs) and have highlighted the
      implication of the JAK/STAT pathway as well as the interleukin 1 (IL-1) signaling
      pathway. Distinct immunologic strategies have been considered to harness the
      immune system or trigger LSC death to allow more CML patients to discontinue TKI
      treatment (so-called functional cure). Successful immunotherapy and TKI
      combination and the optimal timing of immunotherapy determination represent major
      challenges for the future.

PMID- 28501912
TI  - Idiopathic retroperitoneal fibrosis: clinical features and long-term renal
      function outcome.
AB  - PURPOSE: To evaluate the long-term renal function outcome of management of
      retroperitoneal fibrosis (RPF)-induced ureteral obstruction. METHODS: Thirty-six
      patients with idiopathic RPF-induced ureteral obstruction were classified
      according to the management type into two groups, group A; managed by indwelling
      JJ stent and group B managed by ureterolysis and omental wrapping (UOR). The
      primary outcome was to define the long-term outcome of management on RF. It was
      evaluated by changes in serum creatinine and estimated GFR (eGFR) using
      Modification of Diet in Renal Disease equation where 20% changes in eGFR is
      considered significant. The second outcome is to compare the outcomes between
      both groups. RESULTS: After 27.5 (1-124) months, median (range) follow-up, median
      (range) serum creatinine increased significantly from 1.5 (0.8-8.1) to 1.6 (1
      12.1) mg/dl (p value =0.04) and eGFR showed non-statistical significant reduction
      from 43 (5-110) to 41 (5-88) ml/min/1.73 m2 (p value =0.3). Eight (22.2%), 12
      (34.4%) and 16 (44.4%) patients showed stable, increased and decreased eGFR.
      Group A showed statistically significant increased serum creatinine and
      insignificant decreased eGFR (p value =0.04 and 0.09), while group B showed
      statistically insignificant changes in serum creatinine and eGFR (p value =0.5
      and 0.9). In group B, nine (21.4%) renal units are still harboring JJ stents.
      CONCLUSION: For idiopathic RPF, UOR avoided indwelling ureteral stents in 78.6%
      of renal units with apparent better long-term renal function outcome.

PMID- 28501910
TI  - Targeting the dominant mechanism of coronary microvascular dysfunction with
      intracoronary physiology tests.
AB  - The coronary microcirculation plays a key role in modulating blood supply to the
      myocardium. Several factors like myocardial oxygen demands, endothelial and
      neurogenic conditions determine its function. Although there is available
      evidence supporting microvascular dysfunction as an important cause of myocardial
      ischaemia, with both prognostic and symptomatic implications, its diagnosis and
      management in clinical practice is still relegated to a second plane. Both
      diagnostic and therapeutic approaches are hampered by the broadness of the
      concept of microvascular dysfunction, which fails addressing the plurality of
      mechanisms leading to dysfunction. Normal microcirculatory function requires both
      structural integrity of the microcirculatory vascular network and preserved
      signalling pathways ensuring adequate and brisk arteriolar resistance shifts in
      response to myocardial oxygen demands. Pathological mechanisms affecting these
      requirements include structural remodelling of microvessels, intraluminal
      plugging, extravascular compression or vasomotor dysregulation. Importantly, not
      every diagnostic technique provides evidence on which of these pathophysiological
      mechanisms is present or predominates in the microcirculation. In this paper we
      discuss the mechanisms of coronary microvascular dysfunction and the
      intracoronary tools currently available to detect it, as well as the potential
      role of each one to unmask the main underlying mechanism.

PMID- 28501914
TI  - Skermanella mucosa sp. nov., isolated from crude oil contaminated soil.
AB  - A novel Gram-stain negative, small rod-shaped bacterium (strain 8-14-6T) was
      isolated from hydrocarbon contaminated desert soil collected from Kuwait. Strain
      8-14-6T grew at 5-37  degrees C, pH 6.0-8.8 and 0-2% (w/v) of NaCl concentration.
      Casein, starch, Tween 20 and Tween 80 were hydrolyzed while urea, chitin, DNA and
      carboxymethyl-cellulose were not hydrolyzed by strain 8-14-6T. The major cellular
      fatty acids were identified as C18:1omega6c/C18:1omega7c, C16:0 and iso
      C16:1I/C14:03-OH. Strain 8-14-6T produced diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an
      unidentified phospholipids, two unidentified lipids and five unidentified amino
      lipids as polar lipids. Genomic G+C content was 73.5 mol %. 16S rRNA gene
      sequence comparisons indicated that strain 8-14-6T represents a member of the
      genus Skermanella within family Rhodospirillaceae of the class
      Alphaproteobacteria. Strain 8-14-6T has a sequence similarity of 98.9% with
      Skermanella rosea M1T, 97.4% with Skermanella aerolata 5416T-32T, 96.9% with
      Skermanella stibiiresistens SB22T and <95.4% with the other two known species of
      the genus Skermanella. The DNA-DNA relatedness values between strain 8-14-6T and
      the type strains of the closely related species were clearly below the 70%
      threshold. From the combination of phenotypic and genotypic characteristics and
      distinct phylogenetic position, the strain is considered to represent a novel
      species of the genus Skermanella, for which the name Skermanella mucosa sp. nov.
      is proposed. The type strain is 8-14-6T (=KEMB 2255-438T =JCM 31590T).

PMID- 28501915
TI  - Role of the Inositol Polyphosphate Multikinase Ipk2 in Regulation of Hyphal
      Development, Calcium Signaling and Secretion in Candida albicans.
AB  - Inositol polyphosphates are a family of inositol derivatives and ubiquitously
      distributed in various organisms. Their generation is catalyzed by inositol
      polyphosphate multikinases, which play essential roles in abundant cellular
      processes. However, little is known about the kinds and functions of inositol
      polyphosphate multikinases in the important fungal pathogen, C. albicans. In this
      study, we identified a C. albicans inositol polyphosphate multikinase, Ipk2. This
      kinase shares the conserved IPK domain and localizes in the nucleus. A strain
      with controllable expression of IPK2 was constructed using the inducible promoter
      of MET3. Down-regulation of IPK2 by addition of methionine and cysteine enhanced
      the ability of hyphal development, increased expression of hypha-specific genes
      and promoted transport of hypha-specific factors. Moreover, this down-regulation
      rendered increase in cytoplasmic calcium levels but decrease in cellular total
      calcium contents, indicating its role in regulation of calcium homeostasis.
      Assays of secretion and macrophage killing further demonstrated that Ipk2
      negatively regulated secretion of degradative enzymes and damage to macrophages.
      This study sheds a novel light on the functions of inositol polyphosphate
      multikinases in fungal organisms.

PMID- 28501917
TI  - A primer on systematic reviews in toxicology.
AB  - Systematic reviews, pioneered in the clinical field, provide a transparent,
      methodologically rigorous and reproducible means of summarizing the available
      evidence on a precisely framed research question. Having matured to a well
      established approach in many research fields, systematic reviews are receiving
      increasing attention as a potential tool for answering toxicological questions.
      In the larger framework of evidence-based toxicology, the advantages and
      obstacles of, as well as the approaches for, adapting and adopting systematic
      reviews to toxicology are still being explored. To provide the toxicology
      community with a starting point for conducting or understanding systematic
      reviews, we herein summarized available guidance documents from various fields of
      application. We have elaborated on the systematic review process by breaking it
      down into ten steps, starting with planning the project, framing the question,
      and writing and publishing the protocol, and concluding with interpretation and
      reporting. In addition, we have identified the specific methodological challenges
      of toxicological questions and have summarized how these can be addressed.
      Ultimately, this primer is intended to stimulate scientific discussions of the
      identified issues to fuel the development of toxicology-specific methodology and
      to encourage the application of systematic review methodology to toxicological
      issues.

PMID- 28501918
TI  - Exercise stress echocardiography in hypertrophic cardiomyopathy.
AB  - In this review, we make a comprehensive summary of exercise stress
      echocardiography in hypertrophic cardiomyopathy (HCM) and practical tips used in
      our hospital. The main objective of performing exercise stress echocardiography
      in patients with HCM is to evaluate left ventricular outflow tract obstruction,
      mitral regurgitation, left ventricular asynergy, and diastolic function during
      exercise. There are limitations to the explanations that can be provided for
      exertional symptoms when resting echocardiography is performed in patients with
      HCM. In contrast, exercise stress echocardiography causes the manifestation of
      findings that are latent at rest, which possibly provides the elucidation of
      symptom etiology. In this article, we focus on the usefulness of exercise stress
      echocardiography in HCM.

PMID- 28501919
TI  - Automated cytological detection of Barrett's neoplasia with infrared
      spectroscopy.
AB  - BACKGROUND: Development of a nonendoscopic test for Barrett's esophagus would
      revolutionize population screening and surveillance for patients with Barrett's
      esophagus. Swallowed cell collection devices have recently been developed to
      obtain cytology brushings from the esophagus: automated detection of neoplasia in
      such samples would enable large-scale screening and surveillance. METHODS:
      Fourier transform infrared (FTIR) spectroscopy was used to develop an automated
      tool for detection of Barrett's esophagus and Barrett's neoplasia in esophageal
      cell samples. Cytology brushings were collected at endoscopy, cytospun onto
      slides and FTIR images were measured. An automated cell recognition program was
      developed to identify individual cells on the slide. RESULTS: Cytology review and
      contemporaneous histology was used to inform a training dataset containing 141
      cells from 17 patients. A classification model was constructed by principal
      component analysis fed linear discriminant analysis, then tested by leave-one
      sample-out cross validation. With application of this training model to whole
      slide samples, a threshold voting system was used to classify samples according
      to their constituent cells. Across the entire dataset of 115 FTIR maps from 66
      patients, whole samples were classified with sensitivity and specificity
      respectively as follows: normal squamous cells 79.0% and 81.1%, nondysplastic
      Barrett's esophagus cells 31.3% and 100%, and neoplastic Barrett's esophagus
      cells 83.3% and 62.7%. CONCLUSIONS: Analysis of esophageal cell samples can be
      performed with FTIR spectroscopy with reasonable sensitivity for Barrett's
      neoplasia, but with poor specificity with the current technique.

PMID- 28501920
TI  - A dramatic blood plasticity in hibernating and 14-day hindlimb unloading Daurian
      ground squirrels (Spermophilus dauricus).
AB  - We compared the effects of hibernation inactivity and 14-day hindlimb unloading
      in non-hibernating period on biochemical, rheological, and hematological
      parameters of blood in Daurian ground squirrels (Spermophilus dauricus). Twenty
      four squirrels were randomly divided into four groups: control (CON), hibernation
      (HIB), post-hibernation (POST), and 14-day hindlimb unloading (HU). The results
      showed that serum enzymes (L-lactate dehydrogenase, alanine aminotransferase, and
      aspartate aminotransferase) activities decreased in HIB, POST, and HU squirrels
      compared with CON. Total protein (including albumin and globulin) maintained in
      HIB but decreased in HU compared with CON. Total cholesterol and high-density
      lipoprotein-cholesterol increased in HIB but maintained in HU and POST compared
      with CON. Meanwhile, serum creatinine decreased and urea increased in HU compared
      with CON. All blood ions concentrations were unchanged in HIB, POST, and HU
      squirrels compared with CON except calcium which increased in HIB compared with
      CON, and phosphorus which increased in HIB and POST compared with CON. Most of
      detected serum biochemical analytes in POST recovered to the CON level. Blood
      viscosity, which was unchanged in all shear rates in HU, increased in HIB and
      recovered in POST in lower shear rates compared with CON. Erythrocyte and
      corpuscular volume decreased in HIB and HU but maintained in POST compared with
      CON. All the routine hematological parameters recovered in POST as compared with
      CON except platelet, which decreased in HIB and POST but maintained in HU
      compared with CON. In conclusion, our results suggested a remarkable ability to
      maintain blood homeostasis in hibernating squirrels.

PMID- 28501916
TI  - MicroRNAs in injury and repair.
AB  - Organ damage and resulting pathologies often involve multiple deregulated
      pathways. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate a multitude
      of genes at the post-transcriptional level. Since their discovery over two
      decades ago, miRNAs have been established as key players in the molecular
      mechanisms of mammalian biology including the maintenance of normal homeostasis
      and the regulation of disease pathogenesis. In recent years, there has been
      substantial progress in innovative techniques to measure miRNAs along with
      advances in targeted delivery of agents modulating their expression. This has
      expanded the scope of miRNAs from being important mediators of cell signaling to
      becoming viable quantitative biomarkers and therapeutic targets. Currently, miRNA
      therapeutics are in clinical trials for multiple disease areas and vast numbers
      of patents have been filed for miRNAs involved in various pathological states. In
      this review, we summarize miRNAs involved in organ injury and repair,
      specifically with regard to organs that are the most susceptible to injury: the
      liver, heart and kidney. In addition, we review the current state of knowledge on
      miRNA biology, miRNA biomarkers and nucleotide-based therapeutics designed to
      target miRNAs to prevent organ injury and promote repair.

PMID- 28501921
TI  - Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia,
      liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in
      rats rendered obese by high fat diet.
AB  - PURPOSE: Obese individuals have higher production of reactive oxygen species,
      which leads to oxidative damage. We hypothesize that cranberry extract (CE) can
      improve this dysfunction in HFD-induced obesity in rats since it has an important
      antioxidant activity. Here, we evaluated the effects of CE in food intake,
      adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors,
      hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal
      day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36)
      fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5%
      (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups
      were killed while the others were subdivided into four groups (n = 12/group):
      animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30
      days or water (SD, HFD). At PN180, animals were killed. RESULTS: HFD group showed
      higher body mass and visceral fat, hypercorticosteronemia, higher liver
      glucocorticoid sensitivity, cholesterol and triglyceride contents and
      microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and
      tissues) and higher protein carbonylation (liver and adipose tissue) compared to
      SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia,
      hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase
      contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation
      (liver and adipose tissue) and accumulation of liver fat compared to HFD group.
      CONCLUSION: Although adiposity was not completely reversed, cranberry extract
      improved the metabolic profile and reduced oxidative damage and steatosis in HFD
      fed rats, which suggests that it can help manage obesity-related disorders.

PMID- 28501923
TI  - Application of objective clinical human reliability analysis (OCHRA) in
      assessment of technical performance in laparoscopic rectal cancer surgery: common
      mistakes and methodological issues.

PMID- 28501922
TI  - SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut
      supplementation.
AB  - PURPOSE: The consumption of Brazil nuts has been associated with benefits to
      lipid metabolism and reductions in total cholesterol and LDL concentrations. They
      are the richest natural source of selenium which has essential functions in human
      physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and
      glucose metabolisms. The aim of this work was to verify the influence of
      polymorphisms in genes for selenoproteins on blood lipid levels after dietary
      supplementation with Brazil nuts in healthy adults. METHODS: The study included
      130 healthy volunteers selected at the University of Sao Paulo, Brazil. They were
      supplemented with one nut a day for 8 weeks, followed by 8 weeks without
      intervention. The following analyses were performed: anthropometric measurements,
      serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels.
      The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041,
      rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins. RESULTS:
      The concentrations of total cholesterol and fasting glucose levels decreased
      after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by
      rs3877899 in SEPP1, with significantly lower levels observed for individuals with
      the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with
      cholesterol concentrations, which were significantly lower for individuals with
      the GG genotype (p = 0.053). CONCLUSIONS: Supplementation with one Brazil nut a
      day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our
      results suggest that rs3877899 might be associated with glucose concentrations
      and rs7579 with cholesterol concentrations. Therefore, the effect of genetic
      variations should be considered in future nutritional interventions evaluating
      the response to Brazil nut supplementation.

PMID- 28501924
TI  - Anterior rectal duplication treated with transanal endoscopic microsurgery.

PMID- 28501925
TI  - Colonoscope-mediated vaginoscopy for diagnostic evaluation of colovaginal
      fistulas.

PMID- 28501926
TI  - An outbreak of Clostridium difficile PCR ribotype 027 in Spain: risk factors for
      recurrence and a novel treatment strategy.
AB  - An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027
      (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in
      the following months. The aim of this study is to describe this outbreak, assess
      risk factors for recurrence of CDI-027 and to analyze the implementation of a
      novel treatment strategy. This is a prospective study of all patients with CDI
      027, from November 2014 to November 2015. The epidemiological data were collected
      daily for each patient. We compared clinical characteristics and treatment
      between patients with and without recurrence of CDI-027. Interestingly, liver
      cirrhosis was present in 22% of the patients, and most of them received
      prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking
      antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27
      (23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the
      risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral
      vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of
      vancomycin) had fewer recurrences (8.6 versus 44.7% [p <= 0.01]; OR, 0.91; 95%
      CI, 0.028-0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We
      report an outbreak of CDI-027, mainly in patients with liver cirrhosis.
      Recurrence of CDI-027 was more common in those patients. A novel approach
      involving high-dose prolonged vancomycin taper as a first-line treatment,
      together with a bundle of outbreak measures, seemed to reduce the number of cases
      of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach
      warrants further investigation.

PMID- 28501927
TI  - Cytokine gene polymorphism associations with congenital cytomegalovirus infection
      and sensorineural hearing loss.
AB  - Cytomegalovirus (CMV) is the most common viral agent of congenital infections and
      a leading nongenetic cause of sensorineural hearing loss (SNHL). The host
      immunologic factors that render a developing foetus prone to intrauterine CMV
      infection and development of hearing loss are unknown. The aim of this study was
      to assess the potential associations between the polymorphisms within cytokine
      and cytokine receptors genes, and the risk of congenital CMV infection, and the
      hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs):
      TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634,
      IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900,
      CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV
      infection and 398 uninfected controls), and related to congenital CMV infection,
      and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964
      TC genotypes were significantly associated with intrauterine CMV infection (aOR =
      2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007,
      respectively). Twenty-two out of 72 congenitally infected newborns had confirmed
      SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing
      loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p =
      0.039, respectively). This is the first study to report an association between
      SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B
      and TNF) and SNHL (CCL2).

PMID- 28501928
TI  - The Behavioral and Social Sciences: Contributions and Opportunities in Academic
      Medicine.
AB  - The Association of American Medical Colleges plays a leading role in supporting
      the expansion and evolution of academic medicine and medical science in North
      America, which are undergoing high-velocity change. Behavioral and social science
      concepts have great practical value when applied to the leadership practices and
      administrative structures that guide and support the rapid evolution of academic
      medicine and medical sciences. The authors are two behavioral and social science
      professionals who serve as academic administrators in academic medical centers.
      They outline their career development and describe the many ways activities have
      been shaped by their work with the Association of American Medical Colleges.
      Behavioral and social science professionals are encouraged to become change
      agents in the ongoing transformation of academic medicine.

PMID- 28501930
TI  - Association of GWAS-Reported Variant rs11196288 near HABP2 with Ischemic Stroke
      in Chinese Han Population.
AB  - A recent genome-wide association analysis identified a novel single nucleotide
      polymorphism locus on chromosome 10q25.3 (rs11196288, near HABP2) associated with
      the risk of early-onset ischemic stroke (IS) in European population, but not with
      late-onset IS. However, the role of this genome-wide association study (GWAS)
      reported variant in ischemic stroke in Chinese Han population remained unknown.
      In our study, 389 adult ischemic stroke patients with an age of onset <60 years
      and 389 matched healthy controls were enrolled to investigate association of
      rs11196288 genotypes with early-onset ischemic stroke and its subtypes; the
      association was further examined in another independent population consisting of
      349 ischemic stroke patients with an age of onset ?60 years and 349 matched
      healthy individuals. Logistic regression analysis showed no significant
      association between rs11196288 and early-onset ischemic stroke (IS), large artery
      atherosclerotic (LAA) stroke, or small vessel disease (SVD) stroke (all P >
      0.050). Nevertheless, in subgroup analysis of the older population, rs11196288
      presented significant effect on late-onset SVD stroke susceptibility in the
      dominant model (GG/GA vs AA, OR 1.70; 95%CI 1.02 to 2.85; P = 0.042). The results
      indicated that the role of rs11196288 polymorphism in ischemic stroke
      susceptibility in Chinese Han population may be different from that in European.
      Larger studies with diverse populations are warranted to confirm and extend our
      findings.

PMID- 28501931
TI  - Effect of allyl isothiocyanate on NF-kappaB signaling in 7,12
      dimethylbenz(a)anthracene and N-methyl-N-nitrosourea-induced mammary
      carcinogenesis.
AB  - BACKGROUND: Inflammation plays a pivotal role in the process of carcinogenesis
      and phytochemicals have anti-inflammatory properties gaining more importance in
      cancer chemoprevention. The present study aimed to investigate the anti
      inflammatory effect of allyl isothiocyanate (AITC) on 7,12
      dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced
      mammary carcinogenesis in female Sprague-Dawley rats. METHODS: RT-PCR and western
      blot analysis showed that inflammatory markers such as NF-kappaB p65, TNF-alpha,
      and IL-6 were overexpressed in mammary tumor tissues. Histological analysis of
      tumor tissues shows abnormality in hematoxylin and eosin (H&E) staining and
      toluidine blue (TB) staining of mast cell content, and lipid accumulation in oil
      red O staining. RESULTS: Administration of AITC (20 mg/kg bw) to carcinogen
      injected rats significantly decreased the expression of NF-kappaB p65, TNF-alpha,
      and IL-6 in mammary tissues. Further, molecular docking study demonstrates the
      binding of AITC to NF-kappaB p65. Remarkably, AITC treatments control the growth
      of cancer cells as clearly evidenced by histopathological analysis. Staining of
      mammary tissues for mast cells and lipids indicates that AITC treatment to
      carcinogen-administrated rats significantly reduced mammary tumorigenesis.
      CONCLUSIONS: The result suggests that AITC has anti-inflammatory potential to
      prevent DMBA- and MNU-induced mammary carcinogenesis in rats.

PMID- 28501932
TI  - Factors affecting serum sclerostin in postmenopausal women.

PMID- 28501929
TI  - Hyponatremia associated with human herpesvirus-6 (HHV-6) encephalitis after
      allogeneic hematopoietic stem cell transplantation: A presentation different from
      HHV-6 myelitis.
AB  - Human herpesvirus-6 (HHV-6) encephalitis and myelitis following allogeneic
      hematopoietic stem cell transplantation (HSCT) is frequently life-threatening. We
      retrospectively evaluated the clinical significance of hyponatremia in cases of
      HHV-6 encephalitis/myelitis. Using an institutional database and medical records,
      we identified and retrospectively analyzed 16 cases of HHV-6 encephalitis and/or
      myelitis after allogeneic HSCT. HHV-6 encephalitis and myelitis were defined as
      the symptoms/signs with HHV-6-DNA in the cerebrospinal fluid. Seizure and memory
      disorder were defined as symptoms/signs of encephalitis, and dysesthesia and
      vesicorectal disorder as those of myelitis. Five patients developed encephalitis
      with or without myelitis, and 11 patients developed myelitis alone. Hyponatremia
      (median 129.1 mEq/L; range 125.9-130.1) was observed in all five patients with
      HHV-6 encephalitis at diagnosis, and values were significantly lower than those
      in patients with HHV-6 myelitis alone (median 137.6; range 134.0-142.2; P <
      0.01). In three of the five patients with encephalitis, the decrease in sodium
      level preceded the clinical onset of encephalitis by one or two days. These
      results suggest that hyponatremia may be an important manifestation of HHV-6
      encephalitis, but not of myelitis, and could be a useful tool for the early
      prediction or diagnosis of HHV-6 encephalitis.

PMID- 28501933
TI  - The influence of MCAT and GPA preadmission academic metrics on interview scores.
AB  - Medical school admissions interviews are used to assess applicants' nonacademic
      characteristics as advocated by the Association of American Medical Colleges'
      Advancing Holistic Review Initiative. The objective of this study is to determine
      whether academic metrics continue to significantly influence interviewers' scores
      in holistic processes by blinding interviewers to applicants' undergraduate grade
      point averages (uGPA) and Medical College Admission Test (MCAT). This study
      examines academic and demographic predictors of interview scores for two
      applicant cohorts at the University of Michigan Medical School. In 2012,
      interviewers were provided applicants' uGPA and MCAT scores; in 2013, these
      academic metrics were withheld from interviewers' files. Hierarchical regression
      analysis was conducted to examine the influence of academic and demographic
      variables on overall cohort interview scores. When interviewers were provided
      uGPA and MCAT scores, academic metrics explained more variation in interview
      scores (7.9%) than when interviewers were blinded to these metrics (4.1%).
      Further analysis showed a statistically significant interaction between cohort
      and uGPA, indicating that the association between uGPA and interview scores was
      significantly stronger for the 2012 unblinded cohort compared to the 2013 blinded
      cohort (beta = .573, P < .05). By contrast, MCAT scores had no interactive
      effects on interviewer scores. While MCAT scores accounted for some variation in
      interview scores for both cohorts, only access to uGPA significantly influenced
      interviewers' scores when looking at interaction effects. Withholding academic
      metrics from interviewers' files may promote assessment of nonacademic
      characteristics independently from academic metrics.

PMID- 28501934
TI  - CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal
      activity.
AB  - CX-4945 is a selective inhibitor of protein kinase CK2 exhibiting clinical
      significance. Its antitumor properties arise from the abrogation of CK2-mediated
      pro-survival cellular pathways. The presented data reveal the influence of CX
      4945 on the growth of yeast cells showing variable potency against Saccharomyces
      cerevisiae deletion strains with different contents of CK2 subunits. The
      catalytic subunit CK2alpha appears to sensitize yeast to the CX-4945 action.
      Moreover, the compound suppresses hyphal growth and cell adhesion of Candida
      albicans, thereby abolishing some hallmarks of invasiveness of the pathogen. It
      is known that cancer patients are more prone to fungal infections. Our data
      unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may
      simultaneously prevent cancer-associated candidiasis.

PMID- 28501935
TI  - Early gastric adenocarcinoma arising within foveolar-type dysplasia in a patient
      with Muir-Torre variant Lynch syndrome.

PMID- 28501936
TI  - Maternal Sensitivity Predicts Fewer Sleep Problems at Early Adolescence for
      Toddlers with Negative Emotionality: A Case of Differential Susceptibility.
AB  - Theory underscores the importance of parenting in sleep development, but few
      studies have examined whether links vary by temperament. To address this gap, we
      tested whether potential links between early maternal sensitivity and early
      adolescent sleep problems varied by child negative emotionality and delay of
      gratification. Using data from the National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development (N = 820), we found
      that high maternal sensitivity predicted fewer bedtime problems and longer sleep
      duration at 6th grade for toddlers with high negative emotionality, whereas low
      maternal sensitivity predicted the reverse. No differences were observed for low
      negative emotionality. Moreover, delay of gratification predicted fewer bedtime
      problems at 6th grade, but did not moderate associations between maternal
      sensitivity, negative emotionality, and sleep. Findings demonstrate that high,
      but not low, negative emotionality renders toddlers differentially susceptible
      and receptive to maternal sensitivity in relation to sleep.

PMID- 28501937
TI  - Expression of PD-L1 in keratoacanthoma and different stages of progression in
      cutaneous squamous cell carcinoma.
AB  - BACKGROUND: Programmed cell death 1 (PD-1) and its ligands (PD-L1) play a major
      role in the immune responses of a variety of cancers. OBJECTIVES: To investigate
      the expression of PD-L1 in different progression forms of cutaneous squamous cell
      carcinoma (cSCC) and keratoacanthoma (KA). METHODS: We performed
      immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen's
      diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using
      the tumour proportion score and staining intensity evaluation. Immunohistology
      scores were statistically analysed. RESULTS: PD-L1 expression of tumour cells as
      well as tumour-infiltrating cells (TILs) was significantly higher in KA and cSCC
      when compared to AK and BD (P = 0.00028 and P = 0.00033, respectively). We
      observed a very strong positive correlation between the PD-L1 protein expression
      of tumour cells of KA and the PD-L1 protein expression of TILs (r = 0.97; P <
      0.0001). A similar correlation was also found for cSCC (r = 0.86; P < 0.0001).
      The percentage of PD-L1 + tumours was 33.3% for KA and 26.9% for cSCC. Similarly,
      the percentage of PD-L1 + TILs in KA and cSCC was 33.3 and 34.6%, respectively.
      CONCLUSIONS: PD-L1 is differently expressed in cSCC and closely related non
      melanoma skin cancer. cSCC exhibit PD-L1 expression in a fourth of cases,
      indicating that PD1/PD-L1 inhibitors might be beneficial in a proportion of
      patients with an inoperable or metastatic cSCC. Unlike AK and BD, TILs and tumour
      cells of KA and cSCC present very similar PD-L1 expression profiles indicating a
      common immune escape mechanism.

PMID- 28501938
TI  - Zoledronic acid renders human M1 and M2 macrophages susceptible to Vdelta2+
      gammadelta T cell cytotoxicity in a perforin-dependent manner.
AB  - Vdelta2+ T cells are a subpopulation of gammadelta T cells in humans that are
      cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen
      containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to
      accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to
      Vdelta2+ T cell cytotoxicity. However, little is known about whether ZA renders
      other, non-malignant cell types susceptible. In this study we focussed on
      macrophages (Mphis), as these cells have been shown to take up ZA. We
      differentiated peripheral blood monocytes from healthy donors into Mphis and then
      treated them with IFN-gamma or IL-4 to generate M1 and M2 Mphis, respectively. We
      characterised these Mphis based on their phenotype and cytokine production and
      then tested whether ZA rendered them susceptible to Vdelta2+ T cell cytotoxicity.
      Consistent with the literature, IFN-gamma-treated Mphis expressed higher levels
      of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mphis expressed higher
      levels of the M2 markers CD206 and chemokine (C-C motif) ligand 18. When treated
      with ZA, both M1 and M2 Mphis became susceptible to Vdelta2+ T cell cytotoxicity.
      Vdelta2+ T cells expressed perforin and degranulated in response to ZA-treated
      Mphis as shown by mobilisation of CD107a and CD107b to the cell surface.
      Furthermore, cytotoxicity towards ZA-treated Mphis was sensitive-at least in part
      to the perforin inhibitor concanamycin A. These findings suggest that ZA can
      render M1 and M2 Mphis susceptible to Vdelta2+ T cell cytotoxicity in a perforin
      dependent manner, which has important implications regarding the use of ZA in
      cancer immunotherapy.

PMID- 28501939
TI  - Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an
      anti-calcitonin receptor antibody, are differentially potent in vitro in high
      grade glioma cell lines derived from glioblastoma.
AB  - We have reported that calcitonin receptor (CTR) is widely expressed in biopsies
      from the lethal brain tumour glioblastoma by malignant glioma and brain tumour
      initiating cells (glioma stem cells) using anti-human CTR antibodies. A
      monoclonal antibody against an epitope within the extracellular domain of CTR was
      raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating
      proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E
      (MMAE), and purified. In the high-grade glioma cell line (HGG, representing
      glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the
      EC50 for mAb2C4:dianthin was 10.0 pM and for mAb2C4:MMAE [antibody drug conjugate
      (ADC)] 2.5 nM, 250-fold less potent. With the cell line U87MG, in the presence of
      SO1861, the EC50 for mAb2C4:dianthin was 20 pM, mAb2C4:gelonin, 20 pM, compared
      to the ADC (6.3 nM), which is >300 less potent. Several other HGG cell lines that
      express CTR were tested and the efficacies of mAb2C4:RIP (dianthin or gelonin)
      were similar. Co-administration of the enhancer SO1861 purified from plants
      enhances lysosomal escape. Enhancement with SO1861 increased potency of the
      immunotoxin (>3 log values) compared to the ADC (1 log). The uptake of antibody
      was demonstrated with the fluorescent conjugate mAb2C4:Alexa Fluor 568, and the
      release of dianthin-30:Alexa Fluor488 into the cytosol following addition of
      SO1861 supports our model. These data demonstrate that the immunotoxins are
      highly potent and that CTR is an effective target expressed by a large proportion
      of HGG cell lines representative of glioma stem cells and isolated from
      individual patients.

PMID- 28501940
TI  - Common extracellular matrix regulation of myeloid cell activity in the bone
      marrow and tumor microenvironments.
AB  - The complex interaction between cells undergoing transformation and the various
      stromal and immunological cell components of the tumor microenvironment (TME)
      crucially influences cancer progression and diversification, as well as endowing
      clinical and prognostic significance. The immunosuppression characterizing the
      TME depends on the recruitment and activation of different cell types including
      regulatory T cells, myeloid-derived suppressor cells, and tumor-associated
      macrophages. Less considered is the non-cellular component of the TME. Here, we
      focus on the extracellular matrix (ECM) regulatory activities that, within the
      TME, actively contribute to many aspects of tumor progression, acting on both
      tumor and immune cells. Particularly, ECM-mediated regulation of tumor-associated
      immunosuppression occurs through the modulation of myeloid cell expansion,
      localization, and functional activities. Such regulation is not limited to the
      TME but occurs also within the bone marrow, wherein matricellular proteins
      contribute to the maintenance of specialized hematopoietic stem cell niches
      thereby regulating their homeostasis as well as the generation and expansion of
      myeloid cells under both physiological and pathological conditions. Highlighting
      the commonalities among ECM-myeloid cell interactions in bone marrow and TME, in
      this review we present a picture in which myeloid cells might sense and respond
      to ECM modifications, providing different ECM-myeloid cell interfaces that may be
      useful to define prognostic groups and to tailor therapeutic interventions.

PMID- 28501941
TI  - Paracrine release of IL-2 and anti-CTLA-4 enhances the ability of artificial
      polymer antigen-presenting cells to expand antigen-specific T cells and inhibit
      tumor growth in a mouse model.
AB  - Accumulating evidence indicates that bead-based artificial antigen-presenting
      cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in
      vitro and in vivo. To date, most conventional aAPCs have been generated by
      coupling an antigen signal (signal 1) and one or two costimulatory signals, such
      as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell
      sized or nanoscale magnetic beads or polyester latex beads. The development of a
      biodegradable scaffold and the combined use of multiple costimulatory signals as
      well as third signals for putative clinical applications is the next step in the
      development of this technology. Here, a novel biodegradable aAPC platform for
      active immunotherapy was developed by co-encapsulating IL-2 and anti-CTLA-4
      inside cell-sized polylactic-co-glycolic acid microparticles (PLGA-MPs) while co
      coupling an H-2Kb/TRP2-Ig dimer and anti-CD28 onto the surface. Cytokines
      (activating signal) and antibodies (anti-inhibition signal) were efficiently co
      encapsulated in PLGA-MP-based aAPCs and co-released without interfering with each
      other. The targeted, sustained co-release of IL-2 and anti-CTLA-4 achieved
      markedly enhanced, synergistic effects in activating and expanding tumor antigen
      specific T cells both in vitro and in vivo, as well as in inhibiting tumor growth
      in a mouse melanoma model, as compared with conventional two-signal aAPCs and IL
      2 or anti-CTLA-4 single-released aAPCs. These data revealed the feasibility and
      importance of the paracrine release of multiple costimulatory molecules and
      cytokines from biodegradable aAPCs and thus provide a proof of principle for the
      future use of polymeric aAPCs for active immunotherapy of tumors and infectious
      diseases.

PMID- 28501942
TI  - Pulmonary nodule classification with deep residual networks.
AB  - : PURPOSE  : Lung cancer has the highest death rate among all cancers in the USA.
      In this work we focus on improving the ability of computer-aided diagnosis (CAD)
      systems to predict the malignancy of nodules from cropped CT images of lung
      nodules. METHODS: We evaluate the effectiveness of very deep convolutional neural
      networks at the task of expert-level lung nodule malignancy classification. Using
      the state-of-the-art ResNet architecture as our basis, we explore the effect of
      curriculum learning, transfer learning, and varying network depth on the accuracy
      of malignancy classification. RESULTS: Due to a lack of public datasets with
      standardized problem definitions and train/test splits, studies in this area tend
      to not compare directly against other existing work. This makes it hard to know
      the relative improvement in the new solution. In contrast, we directly compare
      our system against two state-of-the-art deep learning systems for nodule
      classification on the LIDC/IDRI dataset using the same experimental setup and
      data set. The results show that our system achieves the highest performance in
      terms of all metrics measured including sensitivity, specificity, precision,
      AUROC, and accuracy. CONCLUSIONS: The proposed method of combining deep residual
      learning, curriculum learning, and transfer learning translates to high nodule
      classification accuracy. This reveals a promising new direction for effective
      pulmonary nodule CAD systems that mirrors the success of recent deep learning
      advances in other image-based application domains.

PMID- 28501944
TI  - Sociodemographic predictors of participation in colorectal cancer screening.
AB  - PURPOSE: Colorectal cancer screening by inviting citizens to complete a test for
      blood in faeces was initiated in Denmark in 2014. We have examined
      sociodemographic predictors that influence participation to identify factors that
      could be targeted to increase compliance. METHODS: National registers were used
      to link data on invitations for colorectal cancer screening in Denmark from 2014
      to 2015. Region of residence, age, gender, immigration status, income,
      educational level and marital status were identified. Logistic regression
      analysis was used to estimate the risk of non-participation for invited citizens
      while adjusting for all other sociodemographic variables. RESULTS: A total of
      854,237 individuals were included in the analysis. The national participation
      proportion was 65.33%, with significant differences between sociodemographic
      groups. Participation proportions were the lowest in non-Western immigrants
      (53.00%), individuals without a partner (54.05%) and those in the lowest income
      quartile (54.65%), with subgroup participation as low as 40.56%. The highest
      participation proportion was seen in individuals in the highest income quartile
      (71.56%). Region of residence, age, gender, educational level, income quartile,
      marital status and immigration status all had statistically significant
      independent differences in risk of non-participation after full model adjustment.
      CONCLUSION: Participation in colorectal cancer screening was high in Denmark in
      2014 and 2015. Large differences in participation were seen between
      sociodemographic subgroups, potentially resulting in social inequality in the
      benefits from screening. Future efforts to increase participation should focus on
      the low compliance subgroups, such as singles, non-Western immigrants and people
      from the lowest socioeconomic groups.

PMID- 28501943
TI  - Protocol for the development of a Core Outcome Set (COS) for hemorrhoidal
      disease: an international Delphi study.
AB  - PURPOSE: Over the last decade, many studies were performed regarding treatment
      options for hemorrhoidal disease. Randomised controlled trials (RCTs) should have
      well-defined primary and secondary outcomes. However, the reported outcome
      measures are numerous and diverse. The heterogeneity of outcome definition in
      clinical trials limits transparency and paves the way for bias. The development
      of a core outcome set (COS) helps minimizing this problem. A COS is an agreed
      minimum set of outcomes that should be measured and reported in all clinical
      trials of a specific disease. The aim of this project is to generate a COS
      regarding the outcome of treatment after hemorrhoidal disease. METHODS: A Delphi
      study will be performed by an international steering group healthcare
      professionals and patients with the intention to create a standard outcome set
      for future clinical trials for the treatment of hemorrhoidal disease. First, a
      literature review will be conducted to establish which outcomes are used in
      clinical trials for hemorrhoidal disease. Secondly, both healthcare professionals
      and patients will participate in several consecutive rounds of online
      questionnaires and a face-to-face meeting to refine the content of the COS.
      DISCUSSION: Development of a COS for hemorrhoidal disease defines a minimum
      outcome-reporting standard and will improve the quality of research in the
      future.

PMID- 28501945
TI  - Macrophage polarization differs between apical granulomas, radicular cysts, and
      dentigerous cysts.
AB  - OBJECTIVES: Apical periodontitis can appear clinically as apical granulomas or
      radicular cysts. There is evidence that immunologic factors are involved in the
      pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous
      cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main
      regulator of tissue homeostasis and differentiation. There are no studies
      comparing macrophage polarization in apical granulomas, radicular cysts, and
      dentigerous cysts. MATERIALS AND METHODS: Forty-one apical granulomas, 23
      radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue
      microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-,
      CD163-, and MRC1-positive macrophages were detected by immunohistochemical
      methods. TMAs were digitized, and the expression of macrophage markers was
      quantitatively assessed. RESULTS: Radicular cysts are characterized by M1
      polarization of macrophages while apical granulomas show a significantly higher
      degree of M2 polarization. Dentigerous cysts have a significantly lower M1
      polarization than both analyzed periapical lesions (apical granulomas and
      radicular cysts) and accordingly, a significantly higher M2 polarization than
      radicular cysts. Macrophage cell density in dentigerous cysts is significantly
      lower than in the periapical lesions. CONCLUSIONS: The development of apical
      periodontitis towards apical granulomas or radicular cysts might be directed by
      macrophage polarization. Radicular cyst formation is associated with an increased
      M1 polarization of infiltrating macrophages. In contrast to radicular cysts,
      dentigerous cysts are characterized by a low macrophage infiltration and a high
      degree of M2 polarization, possibly reflecting their developmental rather than
      inflammatory origin. CLINICAL RELEVANCE: As M1 polarization of macrophages is
      triggered by bacterial antigens, these results underline the need for sufficient
      bacterial clearance during endodontic treatment to prevent a possible M1
      macrophage-derived stimulus for radicular cyst formation.

PMID- 28501946
TI  - Application of International Caries Detection and Assessment System (ICDAS) and
      Caries Management by Risk Assessment (CAMBRA) systems in child cancer patients: a
      clinical case report.
AB  - BACKGROUND: Leukaemia represents 30-40% of all paediatric malignant tumours and
      is the main cause of death in patients aged <15 years. One of the main
      complications in these patients is infection, which may often occur in the oral
      cavity. Chemotherapy-related oral health problems may be reduced by oral
      healthcare strategies based on the International Caries Detection and Assessment
      System (ICDAS) and Caries Management by Risk Assessment (CABRA). CASE REPORT: A
      case is reported of a 14-year-old girl treated for leukaemia who presented with
      established dental caries lesions which were classified and treated according to
      ICDAS and CABRA protocols. After three, no new caries was observed. FOLLOW-UP AND
      CONCLUSION: ICDAS and CAMBRA provide useful and effective guidance for the
      avoidance of dental and systemic problems. Their introduction into standard
      practice could reduce the legal difficulties derived from dental treatment in
      these patients.

PMID- 28501947
TI  - Current status of superficial pharyngeal squamous cell carcinoma in Japan.
AB  - BACKGROUND: To investigate the status and treatment of superficial pharyngeal
      squamous cell carcinoma in Japan. METHODS: We analyzed all cases diagnosed
      between 2011 and 2013, as recorded in the national database of hospital-based
      cancer registries. We extracted data on patient sex, age, tumor locations,
      histology, presentation routes, initial treatments, and TNM stages. Additionally,
      we compared the characteristics of pharyngeal carcinoma to those of esophageal
      cancer. RESULTS: A total of 16,521 oropharyngeal and hypopharyngeal cancers from
      409 institutions were included. Diagnosis of Tis tumors was infrequent, and both
      cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis
      diseases were the most commonly detected during follow-up examinations for other
      diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared
      to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients
      comprised an equally high proportion of men (94 vs 92%, respectively). The most
      common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas
      T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal
      cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%).
      The proportion of Tis tumors diagnosed at individual institutions showed a
      positive correlation with the number of endoscopic treatments (r = 0.32, P <
      0.001) and the number of esophageal cancer cases (r = 0.37, P < 0.001).
      CONCLUSION: Our national database study elucidated the current characteristics of
      superficial pharyngeal squamous cell carcinoma patients in Japan. Further
      improvements in early diagnosis and standardized treatments are warranted.

PMID- 28501948
TI  - Corneal tomography and biomechanics in primary pterygium.
AB  - PURPOSE: To study the Scheimpflug's imaging and corneal biomechanics in primary
      pterygium. METHODS: A prospective observational study of 55 patients with
      unilateral primary nasal pterygium was done. The normal fellow eyes of patients
      with pterygium were taken as controls. Clinical parameters noted included visual
      acuity, values of corneal curvature by doing Scheimpflug imaging, wavefront
      aberrations in terms of higher and lower-order aberrations and corneal hysteresis
      (CH) as well as corneal resistance factor (CRF) values by using ocular response
      analyzer. RESULTS: Of the total 55 patients, mean age was 43.0 + 11.4 years
      (range: 20-72 years). Mean LogMar uncorrected visual acuity in pterygium eyes and
      control eyes was 0.21 + 0.20 and 0.12 + 0.15, respectively (p = 0.016). On
      Scheimpflug imaging the mean anterior corneal curvature values (Ka1/Ka2 D) were
      41.09 + 3.38/44.33 + 2.29 in pterygium eyes, 43.13 + 1.79/43.98 + 2.17 in control
      eyes (p < 0.0005) and mean posterior corneal curvature (Kp1/Kp2 D) values were
      6.14 + 0.39/6.53 + 0.43 in pterygium eyes and 6.13 + 0.28/6.46 + 0.47 in control
      eyes (p > 0.05). Analysis of corneal aberrations showed significantly higher
      corneal wavefront aberrations in pterygium eyes. Highest correlation of corneal
      astigmatism was noted with corneal area encroached by pterygium (rho = 0.540 for
      LOA and 0.553 for HOA) and distance from pupillary center (rho = 0.531 for LOA
      and 0.564 for HOA). Corneal biomechanical parameters including CH and CRF were
      found to be lower in the pterygium eyes, though not statistically significant (p
      value 0.60 and 0.59, respectively). CONCLUSION: Pterygium leads to deterioration
      of visual performance not only by causing refractive and topographic changes but
      also by causing a significant increase in corneal wavefront aberrations.

PMID- 28501950
TI  - Focus on severe infections.

PMID- 28501951
TI  - Video laryngoscopy for ICU intubation: should it be standard of care?

PMID- 28501949
TI  - Relationship between intracranial internal carotid artery calcification and
      enlarged cerebral perivascular space.
AB  - PURPOSE: The association between intracranial internal carotid artery (IICA)
      calcification and lacunes, white matter hyperintensity (WMH), and cerebral
      microbleeds (CMBs) has been well researched. However, enlarged cerebral
      perivascular space (PVS) has not yet been reported to correlate with intracranial
      internal carotid artery calcification. Therefore, the primary aim of this study
      was to investigate the relationship between IICA calcification and enlarged PVS.
      METHODS: A total of 189 patients with ischemic stroke in the middle cerebral
      artery territory who presented within 7 days of ictus from 2012 to 2015 were
      enrolled respectively. All patients were required to have undergone head computed
      tomography, magnetic resonance imaging, susceptibility-weighted magnetic
      resonance imaging, magnetic resonance angiography, or computed tomography
      angiography. Clinical characteristics were recorded. IICA calcification and
      enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes,
      WMH, and CMBs was recorded. RESULTS: Of the 189 patients, 63.5% were male. Mean
      age of the patients was 68.6 +/- 12.2 years. There were 104 patients with IICA
      calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity
      were significantly associated with IICA calcification (P < 0.05). Multivariate
      logistic regression analysis showed that age, diabetes mellitus, and lacunes were
      independent predictors of IICA calcification (P < 0.05). A lower risk of IICA
      calcification was found in patients with a higher enlarged PVS score (P = 0.004).
      CONCLUSION: Higher enlarged PVS scores were associated with a lesser degree of
      IICA calcification. There appears to be a relationship between reduced risk of
      IICA calcification and enlarged PVS.

PMID- 28501952
TI  - Final adult height in long-term growth hormone-treated achondroplasia patients.
AB  - : The objective of this study was to evaluate the gain in final height of
      achondroplasia (ACH) patients with long-term growth hormone (GH) treatment. We
      analyzed medical data of 22 adult patients (8 males and 14 females) treated with
      GH at a dose of 0.05 mg/kg/day. Optionally, tibial lengthening (TL) was performed
      with the Ilizalov method in 15 patients and TL as well as femoral lengthening
      (FL) in 6 patients. Concomitant gonadal suppression therapy with buserelin
      acetate was applied in 13 patients. The mean treatment periods with GH were 10.7
      +/- 4.0 and 9.3 +/- 2.5 years for males and females, respectively. GH treatment
      augmented the final height +0.60 +/- 0.52 SD (+3.5 cm) and +0.51 +/- 1.29 SD
      (+2.8 cm) in males and females compared to non-treated ACH patients,
      respectively. Final height of ACH patients that underwent GH and TL increased
      +1.72 +/- 0.72 SD (+10.0 cm) and +1.95 +/- 1.34 SD (+9.8 cm) in males and
      females, respectively. GH, TL, and FL increased their final height +2.97 SD
      (+17.2 cm) and +3.41 +/- 1.63 SD (+17.3 cm) in males and females, respectively.
      Gonadal suppression therapy had no impact on final height. CONCLUSIONS: Long-term
      GH treatment contributes to 2.6 and 2.1% of final adult height in male and female
      ACH patients, respectively.

PMID- 28501953
TI  - Evaluating the contributions of muscle activity and joint kinematics to weight
      perception across multiple joints.
AB  - Perceived heaviness is clearly a function of muscle activity: objects feel heavy,
      in part because they are lifted with more force than lighter feeling objects.
      Recent research showed that participants scale their perceptions to the ratio of
      muscle activity to lift acceleration during elbow lifts (Waddell et al. J Exp
      Psychol Hum Percept Perform 42:363-374, 2016). The current study sought
      psychophysiological functions relating perceived heaviness to EMG and peak lift
      acceleration across multiple lifts employing different muscles as prime movers.
      Participants lifted objects with three arm lifts-shoulder, elbow, and wrist-and
      reported perceived heaviness. In each lift, EMG was recorded from the anterior
      deltoid, biceps brachii, and forearm flexors, and peak angular acceleration was
      recorded about each joint. The resulting psychophysiological functions revealed
      the hypothesized ratio of muscle activity to peak lift acceleration in all lifts.
      Principal component regressions showed that the EMG of the forearm flexors and
      peak acceleration of the lifting joint were most relevant for perceived
      heaviness. The special role of forearm flexors in perceiving heaviness across
      different lifts was interpreted in terms of the invariant structure of the
      inertia tensor about the wrist.

PMID- 28501954
TI  - Complete genome sequence of longan witches' broom-associated virus, a novel
      member of the family Potyviridae.
AB  - The complete genome sequence of a new virus isolated from a longan (Dimocarpus
      longan Lour.) plant showing witches' broom syndrome was determined. The viral
      genome is composed of a monopartite single-stranded RNA of 9,428 nucleotides
      excluding the 3' poly(A) tail and contains one large single open reading frame
      encoding a polyprotein of 3086 amino acids. BLAST searches of protein databases
      showed that the encoded polyprotein has a maximum amino acid sequence identity of
      35% (with 85% coverage) to that of the isolate Minnesota of rose yellow mosaic
      virus (RoYMV; family Potyviridae; genus not assigned). Molecular and phylogenetic
      analysis of the genome and encoded protein sequences showed that the identified
      virus has the general features that are characteristic of members of the family
      Potyviridae although it has extremely low sequence similarity to known members of
      the family Potyviridae. The name longan witches' broom-associated virus (LWBaV)
      is proposed for this new virus, which may be considered a member of a new genus
      in the family Potyviridae.

PMID- 28501955
TI  - A case of arteriovenous fistula of the cauda equina fed by the proximal radicular
      artery: anatomical features and treatment precautions.
AB  - PURPOSE: Arteriovenous fistula (AVF) of the cauda equina (CE) fed by the proximal
      radicular artery (PRA) is very rare, and the differentiation from that of the
      filum terminale (FT) is important to avoid treatment-related injury to the CE
      when endovascular treatment is selected. The authors describe a case of AVF of
      the CE fed by the PRA, demonstrate the anatomical features and discuss the
      treatment precautions. METHODS: A 69-year-old man presented with a transient
      weakness of lower limbs. Spinal angiography and magnetic resonance (MR) imaging
      revealed AVF, of which the feeding artery arose from the anterior spinal artery
      (ASA), forming the fistula at L2 level to be drained into the longitudinal venous
      trunk. Under a tentative diagnosis of AVF of the FT, endovascular treatment was
      attempted but failed due to impossible catheterization into the ASA. Therefore,
      surgery was performed. RESULTS: Intraoperative finding revealed that the feeding
      artery and draining vein were not on the FT but on the CE, resulting in the
      proper diagnosis of AVF of the CE. Surgical clips were applied to the draining
      vein closest to the fistula, and postoperatively the symptom improved gradually.
      Although we thoroughly reevaluated spinal angiography and MR images
      postoperatively, AVF of the CE fed by the PRA and that of the FT were not
      distinguishable. CONCLUSIONS: The authors described a case of AVF of the CE fed
      by the PRA and demonstrated the difficulty of the differentiation from that of
      the FT. The utmost precautions are necessary when endovascular treatment is
      selected.

PMID- 28501956
TI  - An in vitro evaluation of sagittal alignment in the cervical spine after
      insertion of supraphysiologic lordotic implants.
AB  - PURPOSE: Cervical spine malalignment can develop as a consequence of degenerative
      disc disease or following spinal surgery. When normal sagittal alignment of the
      spine is disrupted, further degeneration may occur adjacent to the deformity. The
      purpose of this study was to investigate changes in lordosis and sagittal
      alignment in the cervical spine after insertion of supraphysiologic lordotic
      implants. METHODS: Eight cadaveric cervical spines (Occiput-T1) were tested. The
      occiput was free to translate horizontally and vertically but constrained from
      angular rotation. The T1 vertebra was rigidly fixed with a T1 tilt of 23 degrees
      . Implants with varying degrees of lordosis were inserted starting with single
      level constructs (C5-C6), followed by two (C5-C7), and three-level (C4-C7)
      constructs. Changes in sagittal alignment, Occ-C2 angle, cervical lordosis (C2
      7), and segmental lordosis were measured. RESULTS: Increasing cage lordosis led
      to global increases in cervical lordosis. As implanted segmental lordosis
      increased, the axial levels compensated by decreasing in lordosis to maintain
      horizontal gaze. An increase in cage lordosis also corresponded with larger
      changes in SVA. CONCLUSION: Reciprocal compensation was observed in the axial and
      sub-axial cervical spine, with the Occ-C2 segment undergoing the largest
      compensation. Adding more implant lordosis led to larger reciprocal changes and
      changes in SVA. Implants with supraphysiologic lordosis may allow for additional
      capabilities in correcting cervical sagittal plane deformity, following further
      clinical evaluation.

PMID- 28501957
TI  - Molecular analysis reveals hidden diversity in Zungaro (Siluriformes:
      Pimelodidade): a genus of giant South American catfish.
AB  - The genus Zungaro contains some of the largest catfish in South America. Two
      valid species are currently recognized: Zungaro jahu, inhabiting the Parana and
      Paraguay basins, and Zungaro zungaro, occurring in the Amazonas and Orinoco
      basins. Analysing Zungaro specimens from the Amazonas, Orinoco, Paraguay and
      Parana basins, based on the sequencing of COI and D-loop, we found at least three
      MOTUs, indicating the existence of hidden diversity within this fish group.
      Considering the ecological and economic values of this fish, our results are
      surely welcomed for its conservation, disclosing new findings on its diversity
      and pointing out the necessity for a detailed taxonomic revision.

PMID- 28501958
TI  - Heightened perception of breast cancer risk in young women at risk of familial
      breast cancer.
AB  - The objective of this study was to explore the factors that influence perceived
      personal risk of developing breast cancer (BC) in younger women (<35) who are
      considering or have undergone bilateral prophylactic mastectomy (BPM).
      Qualitative interviews guided by interpretative phenomenological analysis were
      conducted with 46 women who had a strong family history of BC and had either
      undergone (n = 26) or were considering (n = 20) BPM. Participants were recruited
      from Australia and New Zealand via hospitals, a genetics clinic, a research
      cohort, a registry and online. Three main themes were identified: information
      that increases fear of BC and death, underlying anxiety and fear and screening
      anxiety. A further two themes: relief following surgery and confusion about
      residual risk following surgery were identified. Younger women (<35) appeared to
      have heightened and sometimes inaccurate perceptions of their BC risk. They
      appeared less relieved of anxiety and fear of developing BC by BPM surgery, in
      comparison to previous research with older women (>40). Those who had undergone
      BPM seemed more anxious about their risk of developing BC than those who were
      still considering surgery. This research has important implications for practice,
      particularly improving communication of accurate risk statistics. Future research
      should examine why some women interpret information differently and explore the
      benefits of psychological consultation for very anxious women.

PMID- 28501959
TI  - Contralateral sinus involvement of surgically treated unilateral allergic fungal
      rhinosinusitis.
AB  - Recurrence of allergic fungal rhinosinusitis (AFRS) is well recognized. However,
      there is scarcity in the literature describing involvement of the non-diseased
      sinuses. We aimed to evaluate the recurrence forms of unilateral AFRS as well as
      to study the possible predictor factors of developing the disease in the
      contralateral side. Patients with exclusive unilateral AFRS from (2010 to 2015)
      were enrolled in multi-institutional case-control study. All patients were
      evaluated after endoscopic sinus surgery for recurrence. Patient's records were
      reviewed for demographics, medical treatment, and clinical, radiological, and
      surgical data. A total of 68 patients were identified. Delayed contralateral
      involvement after the initial surgery was found in 30.8% with mean duration of
      recurrence 16.9 months. A significant association was found with the presence of
      pre-operative contralateral symptoms and signs of inflammation (OR 3.49, 95% CI
      1.19-10.22, p value 0.02). Post-operative use of budesonide irrigation was
      associated with less contralateral involvement (OR 0.11, 95% CI 0.01-0.87, p
      value 0.01). Association of other variables like: comorbidities, perioperative
      use of systemic steroid, radiological signs, extent of surgery, additional
      surgery to the contralateral side, and post-operative use of systemic steroids
      did not show statistical significance. Involvement of the contralateral sinuses
      in 30% of unilateral AFRS cases is considered significant. The non-diseased
      sinuses should be involved in the routine endoscopic examination and post
      operative treatment. Further studies are necessary to investigate the possibility
      of prophylactic surgical intervention of the non-diseased sinuses.

PMID- 28501960
TI  - A modified minimally invasive technique for intra-articular displaced calcaneal
      fractures fixed by transverse and axial screws.
AB  - The management of displaced, intra-articular calcaneal fracture represents a
      surgical challenge to even an experienced orthopedic surgeon. Plate
      osteosynthesis using an extended lateral approach is complicated by soft tissue
      problems, while those treated by closed reduction and percutaneous pinning cannot
      address all the intra-articular fragments sufficiently. The objective of our
      study is to evaluate restoration of subtalar joint and long-term functional
      outcomes in intra-articular displaced calcaneal fractures treated with transverse
      subcondral screws through a small incision on lateral aspect of calcaneus and
      percutaneously placed axial screws through the calcaneal tuberosity. Forty-five
      intra-articular calcaneal fractures were managed with this minimally invasive
      technique. Calcaneal height, width, length, Bohler's angle, and Gissane angle
      were measured preoperatively and last follow-up visit. Functional outcomes were
      assessed on the basis of American Orthopedic Foot and Ankle Society (AOFAS)
      ankle/hind foot score. Preoperative calcaneal length, height, width, Bohler's
      angle, and Gissane angle were improved from 68.62 +/- 2.64 to 72.44 +/- 2.63 mm,
      39.28 +/- 2.72 to 32.37 +/- 2.65 mm, 47.04 +/- 2.56 to 49.55 +/- 2.45 mm, 12.66
      degrees  +/- 2.86 degrees  to 26.93 degrees  +/- 2.57 degrees , 123.91 degrees 
      +/- 3.13 degrees  to 96.06 degrees  +/- 3.92 degrees , respectively, after
      surgery with P value <0.001. There were 21 (46.7%) excellent, 17 (37.8%) good, 4
      (8.8%) fair, and 3 (6.7%) poor outcomes based on AOFAS ankle/hindfoot scores.
      Time to unite the fracture was 11.06 +/- 1.82 weeks (range 8-16 weeks), and all
      fractures were united without major complications. Minimally invasive technique
      through a small incision on lateral aspect of calcaneus gives a moderately good
      exposure for anatomical restoration of Sander's type II and III calcaneal
      fractures fixed with both transverse and axial screws under fluoroscopic
      guidance.

PMID- 28501962
TI  - Arthrodesis of the thumb carpometacarpal joint using a quadrangular plate:
      surgical technique and long-term results of 70 patients.
AB  - PURPOSE: To assess the long-term results of trapeziometacarpal arthrodesis using
      a quadrangular plate, regarding clinical, radiological and functional outcomes,
      as well as development of complications. MATERIAL AND METHOD: From 2005 to 2015,
      70 patients were treated at our institution for primary osteoarthrosis of thumb
      carpometacarpal joint performing a trapeziometacarpal arthrodesis. A total of 85
      arthrodesis were carried out using a titanium quadrangular plate (Proflyle plate,
      Stryker(r), Kalamazoo MI, USA), without grafting in any case. Pre- and
      postoperative functional data were assessed at the outpatient clinics using DASH,
      MWS and VAS. All patients were asked for their ability to perform basic daily
      activities before and after surgery. All patients were also asked about
      satisfaction and their return to their jobs after surgery. Pre- and postoperative
      radiological data were also assessed. RESULTS: There were 59 females and 11 males
      with an average age of 55 years (range 44-60). In 66 cases arthrodesis was
      carried out in the dominant hand, in 45 cases the right thumb was involved, and
      in 40 the left thumb was involved; in 15 cases arthrodesis was carried out
      bilaterally. Preoperative average DASH score was 64 (range 50-85), postoperative
      average score was 25 (range 5-61). Regarding MWS, 51 patients obtained excellent
      results, 15 patients obtained good results and 4 patients referred poor results.
      The preoperative average score of VAS was 6 (range 5-10), which decrease to an
      average of 2 (range 0-3) after surgery; all those differences were statistically
      significant. All patients reported a mild loss of motion; however, all of them
      reported improvement to carry out daily activities. There were four cases of
      nonunion because of failure of fixation and two cases with dysesthetic scar.
      There was no development of osteoarthritis in adjacent joints. The average follow
      up was 60 months. CONCLUSIONS: The use of quadrangular plates for arthrodesis of
      the trapeziometacarpal joint is a safety and reproducible technique with a low
      rate of complications. Arthrodesis decreases pain and improves function in
      patients with primary osteoarthritis of the thumb carpometacarpal joint; in spite
      of a mild loss of motion, patients are satisfied with this procedure.

PMID- 28501961
TI  - Risk factors for local recurrence from atypical cartilaginous tumour and
      enchondroma of the long bones.
AB  - INTRODUCTION: The purpose of our study is to verify possible clinical and
      radiological findings with regard to distinguishing enchondroma from atypical
      cartilaginous tumour (ACT). In addition, this study determined risk factors that
      are associated with local recurrence of enchondroma or ACT treated with
      curettage. MATERIALS AND METHODS: We retrospectively reviewed the records of 54
      patients with enchondroma and 35 patients with ACT of the long bones treated by
      curettage between 1986 and 2015. The minimum follow-up was 18 months. The
      relationship between clinical and radiological factors and the tumour type or
      local recurrence was assessed using Chi-square test or Fischer exact test.
      RESULTS: Endosteal scalloping (p = 0.004) and soft tissue extension (p = 0.017)
      were shown to statistically favour ACT over enchondroma; by contrast, pain (p =
      0.034) was more frequent in enchondroma compared to ACT. All patients with
      enchondroma had no local recurrence; in contrast, local recurrence occurred in
      four patients with ACT (11%). Soft tissue extension (p = 0.049) and the diagnosis
      of ACT (p = 0.021) were associated with an increased risk of local recurrence. We
      had a disease progression in three of four patients with local recurrence, and
      these had higher histological grade than the original tumour. DISCUSSION: Our
      data show that endosteal scalloping and soft tissue extension could be helpful in
      the differential diagnosis between enchondroma and ACT. We suggest following only
      those patients with ACT after surgery to identify any possible recurrence and, in
      case of recurrence, treat these patients with resection for the risk of disease
      progression.

PMID- 28501963
TI  - Salinity-driven decadal changes in phytoplankton community in the NW Arabian Gulf
      of Kuwait.
AB  - Evaluation of hydrological data obtained between 2000 and 2013 from a time series
      station in Kuwait Bay (station K6) and an offshore southern location (station 18)
      off Kuwait showed drastic increase in salinity by 6 units. We tested the
      hypothesis that increased salinity impacted phytoplankton community
      characteristics in these semiarid waters. The Arabian Gulf receives seasonal
      freshwater discharge in the north via Shatt Al-Arab estuary with a peak during
      March-July. A north to south gradient in the proportion of the freshwater exists
      between station A in the vicinity of Shatt Al-Arab estuary and station 18 in the
      southern offshore area. At station A, the proportion of freshwater was the
      highest (25.6-42.5%) in 1997 but decreased to 0.8-4.6% by 2012-2013. The
      prevailing hyperhaline conditions off Kuwait are attributed to decrease in the
      river flow. Phytoplankton data showed a decrease in the number of constituent
      taxa in the last one decade from 353 to 159 in the Kuwait Bay and from 164 to 156
      in the offshore area. A shift in their biomass was caused by a decrease in diatom
      species from 243 to 92 in the coastal waters and from 108 to 83 in the offshore
      areas with a concomitant increase of smaller algae. Mutivariate agglomerative
      hierarchical cluster analysis, non-metric multi-dimensional scaling, and one-way
      analysis of similarity analyses on phytoplankton data at different taxonomic
      levels confirmed significant changes in their community organization on a decadal
      scale. These evidences support our hypothesis that the salinity-related
      environmental changes have resulted in a coincidental decrease in species
      diversity and significant changes in phytoplankton community between the years
      2000-2002 and 2012-2013, off Kuwait. This in turn would affect the pelagic
      trophodynamics as evident from a drastic decrease in the catch landings of
      Tenulosa ilisha (Suboor), Carangoides sp. (Hamam), Otolithes ruber (Nowaiby),
      Parastromateus niger (Halwaya), and Epinephelus coioides (Hamoor) in Kuwait.

PMID- 28501965
TI  - Using a "Positive Deviance" Framework to Discover Adaptive Risk Reduction
      Behaviors Among High-Risk HIV Negative Black Men Who Have Sex with Men.
AB  - Despite the high incidence of HIV among young Black MSM in the United States and
      engagement in high risk behaviors, many men in this group avoid infection. This
      suggests that some men may engage in systematic risk reduction behaviors when not
      always using condoms or abstaining from substances. Using a "positive deviance"
      framework, we conducted qualitative interviews with HIV-negative, Black MSM
      between 25 and 35 who reported unprotected anal sex and drug use in the past six
      months or current heavy drinking (N = 29) to discover behaviors that could
      facilitate remaining HIV-uninfected. Findings showed that MSM who remain HIV
      negative despite continuing to engage in high-risk behaviors may be engaging in
      adaptive risk reduction behaviors that, through successive decisions and advance
      planning along the timeline to a sexual event, could lead to increased condom
      use, avoidance or delay of a risky sexual event, or reduction of HIV positive
      partners.

PMID- 28501964
TI  - Consensus statement: Supporting Safer Conception and Pregnancy For Men And Women
      Living with and Affected by HIV.
AB  - Safer conception interventions reduce HIV incidence while supporting the
      reproductive goals of people living with or affected by HIV. We developed a
      consensus statement to address demand, summarize science, identify information
      gaps, outline research and policy priorities, and advocate for safer conception
      services. This statement emerged from a process incorporating consultation from
      meetings, literature, and key stakeholders. Three co-authors developed an outline
      which was discussed and modified with co-authors, working group members, and
      additional clinical, policy, and community experts in safer conception, HIV, and
      fertility. Co-authors and working group members developed and approved the final
      manuscript. Consensus across themes of demand, safer conception strategies, and
      implementation were identified. There is demand for safer conception services.
      Access is limited by stigma towards PLWH having children and limits to provider
      knowledge. Efficacy, effectiveness, safety, and acceptability data support a
      range of safer conception strategies including ART, PrEP, limiting condomless sex
      to peak fertility, home insemination, male circumcision, STI treatment, couples
      based HIV testing, semen processing, and fertility care. Lack of guidelines and
      training limit implementation. Key outstanding questions within each theme are
      identified. Consumer demand, scientific data, and global goals to reduce HIV
      incidence support safer conception service implementation. We recommend that
      providers offer services to HIV-affected men and women, and program
      administrators integrate safer conception care into HIV and reproductive health
      programs. Answers to outstanding questions will refine services but should not
      hinder steps to empower people to adopt safer conception strategies to meet
      reproductive goals.

PMID- 28501966
TI  - From method to hermeneutics: which epistemological framework for narrative
      medicine?
AB  - The past 10 years have seen considerable developments in the use of narrative in
      medicine, primarily through the emergence of the so-called narrative medicine. In
      this article, I question narrative medicine's self-understanding and contend that
      one of the most prominent issues is its lack of a clear epistemological
      framework. Drawing from Gadamer's work on hermeneutics, I first show that
      narrative medicine is deeply linked with the hermeneutical field of knowledge.
      Then I try to identify which claims can be legitimately expected from narrative
      medicine, and which ones cannot be. I scrutinize in particular whether narrative
      medicine can legitimately grasp the patient's lived experience of his or her
      illness. In the last section of this article, I begin to explore the potential
      usefulness of this epistemological clarification. This analysis allows for a
      further understanding of what is really at stake with narrative medicine, and
      thus to identify when it may be convenient, and when it may not. Furthermore,
      this clarification opens up promising new possibilities of dialogue with critics
      of the field. I conclude that narrative medicine finds its proper place as a
      possible tool available to mediate dialogue, which is at the heart of the
      clinical encounter in medical practice.

PMID- 28501967
TI  - Plaque Tissue Morphology-Based Stroke Risk Stratification Using Carotid
      Ultrasound: A Polling-Based PCA Learning Paradigm.
AB  - Severe atherosclerosis disease in carotid arteries causes stenosis which in turn
      leads to stroke. Machine learning systems have been previously developed for
      plaque wall risk assessment using morphology-based characterization. The
      fundamental assumption in such systems is the extraction of the grayscale
      features of the plaque region. Even though these systems have the ability to
      perform risk stratification, they lack the ability to achieve higher performance
      due their inability to select and retain dominant features. This paper introduces
      a polling-based principal component analysis (PCA) strategy embedded in the
      machine learning framework to select and retain dominant features, resulting in
      superior performance. This leads to more stability and reliability. The automated
      system uses offline image data along with the ground truth labels to generate the
      parameters, which are then used to transform the online grayscale features to
      predict the risk of stroke. A set of sixteen grayscale plaque features is
      computed. Utilizing the cross-validation protocol (K = 10), and the PCA cutoff of
      0.995, the machine learning system is able to achieve an accuracy of 98.55 and
      98.83%corresponding to the carotidfar wall and near wall plaques, respectively.
      The corresponding reliability of the system was 94.56 and 95.63%, respectively.
      The automated system was validated against the manual risk assessment system and
      the precision of merit for same cross-validation settings and PCA cutoffs are
      98.28 and 93.92%for the far and the near wall, respectively.PCA-embedded
      morphology-based plaque characterization shows a powerful strategy for risk
      assessment and can be adapted in clinical settings.

PMID- 28501968
TI  - Effect of Parachute Jump in the Psychophysiological Response of Soldiers in Urban
      Combat.
AB  - The study of organic and psychological response during combat situations has been
      poorly reported despite its importance for soldiers training and specific
      instruction, so it was proposed as aim of the present investigation to analyze
      the effect of a tactical parachute simulated jump in psycho-physiological
      response of paratroopers' warfighters during an urban combat simulation. 19 male
      paratroopers (31.9 +/- 6.2 year old; 173.6 +/- 5.3 cm; 73.8 +/- 8.3 Kg) of the
      Spanish Army were divided in two groups: parachute jump group (n:11) that
      conducted a simulated parachute jump and a urban combat maneuver and a non
      parachute jump group (n:8) that only conducted an urban combat maneuver. We
      analyzed before and after the maneuver the rated perceived exertion, legs
      strength manifestation, blood lactate, cortical activation, heart rate
      variability, blood oxygen saturation and pressure, skin temperature, fine motor
      skills, and anxiety state. A tactical parachute simulated jump prior to an urban
      combat maneuver produce significantly (p < 0.05) higher heart rate and decrease
      in specific fine motor skills in comparison with no jump situation in
      professional Army paratroopers. Independently of the parachute jump, an urban
      combat maneuver produces a significant increase in rated perceived exertion,
      blood lactate, heart rate, legs strength, sympathetic modulation and anxiety
      response as well as a significant decrease in blood oxygen saturation and
      parasympathetic modulation.

PMID- 28501970
TI  - Cancer Center Volume and Type Impact Stage-Specific Utilization of Neoadjuvant
      Therapy in Rectal Cancer.
AB  - BACKGROUND: Neoadjuvant chemoradiation reduces local recurrence in locally
      advanced rectal cancer, and adherence to national and societal recommendations
      remains unknown. OBJECTIVE: To determine variability in guideline adherence in
      rectal cancer treatment and investigate whether hospital volume correlated with
      variability seen. DESIGN: We performed a retrospective analysis using the
      National Cancer Database rectal cancer participant user files from 2005 to 2010.
      Stage-specific predictors of neoadjuvant chemotherapy and radiation use were
      determined, and variation in use across hospitals analyzed. Hospitals were ranked
      based on likelihood of preoperative therapy use by stage, and observed-to
      expected ratios for neoadjuvant therapy use calculated. Hospital outliers were
      identified, and their center characteristics compared. RESULTS: A total of 23,488
      patients were identified at 1183 hospitals. There was substantial variability in
      the use of neoadjuvant chemoradiation across hospitals. Patients managed outside
      clinical guidelines for both stage 1 and stage 3 disease tended to receive
      treatment at lower-volume, community cancer centers. CONCLUSIONS: There is
      substantial variability in adherence to national guidelines in the use of
      neoadjuvant chemoradiation for rectal cancer across all stages. Both hospital
      volume and center type are associated with over-treatment of early-stage tumors
      and under-treatment of more invasive tumors. These findings identify a clear need
      for national quality improvement efforts in the treatment of rectal cancer.

PMID- 28501969
TI  - Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment.
AB  - This paper reviews the current status of our understanding of the epidemiology,
      diagnosis, and management of the continuum of pancreatic diseases from acute and
      recurrent acute pancreatitis to chronic pancreatitis and the diseases that are
      often linked with pancreatitis including diabetes mellitus and pancreatic cancer.
      In addition to reviewing the current state of the field, we identify gaps in
      knowledge that are necessary to address to improve patient outcomes in these
      conditions.

PMID- 28501972
TI  - Genetic variation of major histocompatibility complex genes in the endangered red
      crowned crane.
AB  - Populations that have drastically decreased in the past often have low genetic
      variation, which may increase the risk of extinction. The genes of major
      histocompatibility complex (MHC) play an important role in the adaptive immune
      response of jawed vertebrates. Maintenance of adaptive genetic diversity such as
      that of MHC genes is important for wildlife conservation. Here, we determined
      genotypes of exon 3 of MHC class IA genes (MHCIA) and exon 2 of MHC class IIB
      genes (MHCIIB) to evaluate genetic variation of the endangered red-crowned crane
      population on Hokkaido Island, Japan, which experienced severe population decline
      in the past. We identified 16 and 6 alleles of MHCIA and MHCIIB, respectively,
      from 152 individuals. We found evidence of a positive selection at the antigen
      binding sites in MHCIA exon 3 and MHCIIB exon 2. The phylogenetic analyses
      indicated evidence of trans-species polymorphism among the crane MHC genes. The
      genetic variability in both classes of MHC genes at the population level was low.
      No geographic structure was found based on the genetic diversity of
      microsatellite and MHC genes. Our study provides useful data for the optimal
      management of the red-crowned crane population in Hokkaido and can contribute to
      future studies on MHC genes of the continental populations of the red-crowned
      crane and other crane species.

PMID- 28501973
TI  - Neuroprotective compounds from Reynoutria sachalinensis.
AB  - Glutamate is a neurotransmitter in central nervous system. Overexpression of
      glutamate leads to oxidative stress, resulting in several neurodegenerative
      disorders that include Alzheimer's disease. The n-hexane fraction of stems and
      ethyl acetate (EtOAc) fraction of flowers of Reynoutria sachalinensis provide
      neuroprotection against glutamate-induced oxidative toxicity in HT22 cells. In
      this study, 1-decanol (1), beta-amyrin (2), dammaran-3beta-ol (3), campesterol
      (4), daucosterol (5), ergosterol peroxide (6), emodin 8-O-beta-D-glucopyranoside
      (7), quercetin (8) and isoquercitrin (9) were isolated from n-hexane fractions of
      stems and EtOAc fractions of flowers of R. sachalinensis. Their neuroprotective
      activity was evaluated by MTT assay. 1-Decanol, campesterol, ergosterol peroxide,
      quercetin and isoquercitrin exhibited neuroprotective activity. These compounds
      decreased reactive oxygen species level, showed anti-oxidant activity with DPPH
      radical and in a H2O2 scavenging assay. Therefore, the neuroprotective activity
      of 1-decanol, campesterol, ergosterol peroxide, quercetin and isoquercitrin are
      associated with antioxidant activity.

PMID- 28501971
TI  - Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A
      Physiopathological Approach.
AB  - Electrolyte and acid-base disturbances are frequent in patients with end-stage
      liver disease; the underlying physiopathological mechanisms are often complex and
      represent a diagnostic and therapeutic challenge to the physician. Usually, these
      disorders do not develop in compensated cirrhotic patients, but with the onset of
      the classic complications of cirrhosis such as ascites, renal failure,
      spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte,
      and acid-base disturbances emerge. Hyponatremia parallels ascites formation and
      is a well-known trigger of hepatic encephalopathy; its management in this
      particular population poses a risky challenge due to the high susceptibility of
      cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting
      of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease
      and resulting from its management make these patients particularly susceptible to
      potassium depletion even in the setting of normokalemia. Acid-base disturbances
      range from classical respiratory alkalosis to high anion gap metabolic acidosis,
      almost comprising the full acid-base spectrum. Because most electrolyte and acid
      base disturbances are managed in terms of their underlying trigger factors, a
      systematic physiopathological approach to their diagnosis and treatment is
      required.

PMID- 28501974
TI  - Proteolytic activities in cortex of apical parts of Vicia faba ssp. minor
      seedling roots during kinetin-induced programmed cell death.
AB  - Programmed cell death (PCD) is a crucial process in plant development. In this
      paper, proteolytically related aspects of kinetin-induced PCD in cortex cells of
      Vicia faba ssp. minor seedlings were examined using morphological, fluorometric,
      spectrophotometric, and fluorescence microscopic analyses. Cell viability
      estimation after 46 MUM kinetin treatment of seedling roots showed that the
      number of dying cortex cells increased with treatment duration, reaching maximum
      after 72 h. Weight of the apical root segments increased with time and was about
      2.5-fold greater after 96 h, while the protein content remained unchanged,
      compared to the control. The total and cysteine-dependent proteolytic activities
      fluctuated during 1-96-h treatment, which was not accompanied by the changes in
      the protein amount, indicating that the absolute protein amounts decreased during
      kinetin-induced PCD. N-ethylmaleimide (NEM), phenylmethylsulfonyl fluoride
      (PMSF), and Z-Leu-Leu-Nva-H (MG115), the respective cysteine, serine, and
      proteasome inhibitors, suppressed kinetin-induced PCD. PMSF significantly
      decreased serine-dependent proteolytic activities without changing the amount of
      proteins, unlike NEM and MG115. More pronounced effect of PMSF over NEM indicated
      that in the root apical segments, the most important proteolytic activity during
      kinetin-induced PCD was that of serine proteases, while that of cysteine
      proteases may be important for protein degradation in the last phase of the
      process. Both NEM and PMSF inhibited apoptotic-like structure formation during
      kinetin-induced PCD. The level of caspase-3-like activity of beta1 proteasome
      subunit increased after kinetin treatment. Addition of proteasome inhibitor MG
      115 reduced the number of dying cells, suggesting that proteasomes might play an
      important role during kinetin-induced PCD.

PMID- 28501975
TI  - Changes in liver perfusion and function before and after percutaneous occlusion
      of spontaneous portosystemic shunt.
AB  - PURPOSE: To evaluate changes in liver perfusion after occlusion of spontaneous
      portosystemic shunt and to analyze mechanisms of liver profile improvement.
      MATERIALS AND METHODS: Liver function changes and portal venous and hepatic
      arterial blood flow were evaluated using perfusion CT before and after shunt
      occlusion in 23 patients who underwent percutaneous occlusion of spontaneous
      portosystemic shunt because of gastric varices (n = 15) or hepatic encephalopathy
      (n = 8). RESULTS: Portal venous blood flow was significantly higher at 1 week
      (278.7 ml/min, 92.7-636.7, p = 0.012), 1 month (290.0 ml/min, 110.1-560.1, p <
      0.001) and 3 months (299.6 ml/min, 156.7-618.5, p = 0.033) after shunt occlusion
      than the baseline (220.9 ml/min, 49.5-566.7). Hepatic arterial liver blood flow
      became lower than the baseline (132.3 ml/min, 47.9-622.3) after shunt occlusion,
      but a significant decrease was observed only at 1 month later (107.9 ml/min, 45.8
      263.6 p = 0.027). Serum albumin concentration became significantly higher than
      the baseline (3.4 mg/dl, 1.9-4.5) at 1 month (3.8 mg/dl, 2.3-4.3, p = 0.018) and
      3 months (3.9 mg/dl, 2.6-4.3, p = 0.024) after shunt occlusion. CONCLUSION: Shunt
      occlusion increases portal venous blood flow and decreases hepatic arterial blood
      flow, thereby improving the liver profile.

PMID- 28501976
TI  - Component Resolved Diagnosis in Hymenoptera Anaphylaxis.
AB  - PURPOSE OF REVIEW: Hymenoptera anaphylaxis is one of the leading causes of severe
      allergic reactions and can be fatal. Venom-specific immunotherapy (VIT) can
      prevent a life-threatening reaction; however, confirmation of an allergy to a
      Hymenoptera venom is a prerequisite before starting such a treatment. Component
      resolved diagnostics (CRD) have helped to better identify the responsible
      allergen. RECENT FINDINGS: Many new insect venom allergens have been identified
      within the last few years. Commercially available recombinant allergens offer new
      diagnostic tools for detecting sensitivity to insect venoms. Additional added
      sensitivity to nearly 95% was introduced by spiking yellow jacket venom (YJV)
      extract with Ves v 5. The further value of CRD for sensitivity in YJV and honey
      bee venom (HBV) allergy is more controversially discussed. Recombinant allergens
      devoid of cross-reactive carbohydrate determinants often help to identify the
      culprit venom in patients with double sensitivity to YJV and HBV. CRD identified
      a group of patients with predominant Api m 10 sensitization, which may be less
      well protected by VIT, as some treatment extracts are lacking this allergen. The
      diagnostic gap of previously undetected Hymenoptera allergy has been decreased
      via production of recombinant allergens. Knowledge of analogies in interspecies
      proteins and cross-reactive carbohydrate determinants is necessary to distinguish
      relevant from irrelevant sensitizations.

PMID- 28501977
TI  - Characterization of mitochondrial prohibitin from Boleophthalmus pectinirostris
      and evaluation of its possible role in spermatogenesis.
AB  - Prohibitin (PHB) is an evolutionarily conserved mitochondrial membrane protein.
      It plays a vital role in cell proteolysis, senescence, and apoptosis and is
      associated with spermatogenesis and sperm quality control in mammals. To study
      the characteristics of the PHB gene and its potential roles during
      spermatogenesis in Boleophthalmus pectinirostris, we cloned a 1153-bp full-length
      cDNA from the testis of B. pectinirostris with an open reading frame of 816 bp,
      which encodes 272 amino acid residues. Real-time quantitative PCR (qPCR) analysis
      revealed the presence of phb mRNA in all the tissues examined, with higher
      expression levels found in the testis, kidney, intestine, and muscle tissues. We
      examined the localization of phb mRNA during spermatogenesis by in situ
      hybridization (ISH), showing that phb mRNA was distributed in the periphery of
      the nucleus in primary and secondary spermatocytes. In spermatid and mature
      sperm, the phb mRNA gradually moved toward one side, where the flagellum is
      formed. Immunofluorescence (IF) results showed co-localization of the PHB and
      mitochondria at different stages during spermatogenesis of B. pectinirostris. The
      signals obtained for PHB decreased as spermatogenesis proceeded; the strongest
      detection signal was found in secondary spermatocytes, with lower levels of
      staining in other stages. Additionally, in the mature germ cells, the PHB signals
      were weak and aggregate in the midpiece of the flagellum.

PMID- 28501978
TI  - Growth performance, oxidative stress, and non-specific immune responses in
      juvenile sablefish, Anoplopoma fimbria, by changes of water temperature and
      salinity.
AB  - Juvenile sablefish, Anoplopoma fimbria (mean length 15.5 +/- 1.9 cm, mean weight
      68.5 +/- 4.8 g), were used to evaluate the effects on growth, oxidative stress,
      and non-specific immune responses by changes of water temperature (8, 10, 12, 14,
      16, 18, and 20  degrees C) and salinity (100 (35.0), 90 (31.5), 80 (28.0), 70
      (24.5), 60 (21.0), 50 (17.5), and 40% (14.0) (0/00)) for 4 months. The growth
      performance was significantly increased at the temperature of 12 and 14  degrees
      C, and the feed efficiency was notably decreased at the temperature of 18 
      degrees C. The growth performance and feed efficiency were also significantly
      decreased at low salinity. The antioxidant responses such as superoxide dismutase
      and catalase were significantly increased by the high temperature and decreased
      by the low salinity. The immune responses such as lysozyme and phagocytosis were
      elevated by the temperature of 18  degrees C and decreased by the salinity of
      50%. The results of this study indicate that the growth performance of juvenile
      sablefish, A. fimbria, is influenced by the temperature and salinity, and the
      excessive temperature and salinity levels can affect the antioxidant and immune
      responses.

PMID- 28501979
TI  - Endocrine cells producing peptide hormones in the intestine of Nile tilapia:
      distribution and effects of feeding and fasting on the cell density.
AB  - Endocrine cells (ECs) act as a luminal surveillance system responding to either
      the presence or absence of food in the gut through the secretion of peptide
      hormones. The aim of this study was to analyze the effects of feeding and fasting
      on the EC peptide-specific distribution along the intestine of Nile tilapia. We
      assessed the density of ECs producing gastrin (GAS), cholecystokinin-8 (CCK-8),
      neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in nine segments
      of the intestine using immunohistochemistry. Our results show that ECs
      immunoreactive to CCK-8, GAS, NPY, and CGRP can be found along all the intestinal
      segments sampled, from the midgut to hindgut, although differences in their
      distribution along the gut were observed. Regarding nutrient status, we found
      that the anterior segments of the midgut seem to be the main site responding to
      luminal changes in Nile tilapia. The NPY+ and CGRP+ EC densities increased in the
      fasted group, while the amount of CCK-8+ ECs were higher in the fed group. No
      effects of fasting or feeding were found in the GAS+ EC densities. Changes in ECs
      density were found only at the anterior segments of the intestine which may be
      due to the correlation between vagus nerve anatomy, EC location, and peptide
      turnover. Lastly, ECs may need to be considered an active cell subpopulation that
      may adapt and respond to different nutrient status as stimuli. Due to the
      complexity of the enteroendocrine system and its importance in fish nutrition,
      much remains to be elucidated and it deserves closer attention.

PMID- 28501980
TI  - Medical comorbidity of binge eating disorder: response.

PMID- 28501981
TI  - Protective Effect of Gentianine, a compound from Du Huo Ji Sheng Tang, against
      Freund's Complete Adjuvant-Induced Arthritis in Rats.
AB  - The anti-inflammatory property of gentianine (GE) aroused our interest. To
      investigate the effect of GE on Freund's complete adjuvant (FCA)-induced
      arthritis in rats was the aim of this study. Adjuvant-induced arthritis (AA) was
      induced by the administration of 0.1 ml FCA in the surface of hind paw.
      Diclofenac sodium (DS) and Fasudil were administered as positive controls.
      Downregulation of cytokines including interleukin-6 (IL-6), interleukin-1 beta
      (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) revealed anti
      inflammatory effect of GE, which was consisted with pathological conditions of
      rat paws. In addition, western blot analysis revealed that GE could strikingly
      suppressed the expressions of Rho/NF-kappaB signaling pathways as well as TGF
      beta/smad-3 pathways. In conclusion, data indicated that GE might contribute to
      treat arthritis as a potential therapeutic candidate.

PMID- 28501982
TI  - Smartphone Applications for Hypertension Management: a Potential Game-Changer
      That Needs More Control.
AB  - PURPOSE OF THE REVIEW: This review article will summarize available data on
      mobile applications for the management of hypertension, by highlighting their
      potential for clinical use, the current limitations and the yet pending issues to
      be addressed in future studies. RECENT FINDINGS: The number of available
      applications related to arterial hypertension and their usage by smartphone
      owners is constantly increasing. However, most applications lack standardization
      and scientific validation, and security flaws could be an important, yet still
      underrated, issue. Small studies showed that treatment strategies based on
      telemonitoring of home blood pressure with mobile applications could improve
      blood pressure control, but there are no data on strong outcomes and the high
      heterogeneity of available studies severely limits the possibility of reaching a
      definitive conclusion on the impact of such strategies. Smartphone applications
      for arterial hypertension represent a great chance to improve management of this
      condition. Results from small studies are promising, but there is a strong need
      for large, long-term, well-designed clinical trials, before these potential
      solutions might be reliably applied in real-life patients' care.

PMID- 28501986
TI  - Cloning and characterization of WRKY gene homologs in Chieh-qua (Benincasa
      hispida Cogn. var. Chieh-qua How) and their expression in response to fusaric
      acid treatment.
AB  - The WRKY transcription factors play an important role in plant resistance for
      biotic and abiotic stresses. In the present study, we cloned 10 WRKY gene
      homologs (CqWRKY) in Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua) using the
      rapid-amplification of cDNA ends (RACE) or homology-based cloning methods. We
      characterized the structure of these CqWRKY genes. Phylogenetic analysis of these
      sequences with cucumber homologs suggested possible structural conservation of
      these genes among cucurbit crops. We examined the expression levels of these
      genes in response to fusaric acid (FA) treatment between resistant and
      susceptible Chieh-qua lines with quantitative real-time PCR. All genes could be
      upregulated upon FA treatment, but four CqWRKY genes exhibited differential
      expression between resistant and susceptible lines before and after FA
      application. CqWRKY31 seemed to be a positive regulator while CqWRKY1, CqWRKY23
      and CqWRKY53 were negative regulators of fusaric resistance. This is the first
      report of characterization of WRKY family genes in Chieh-qua. The results may
      also be useful in breeding Chieh-qua for Fusarium wilt resistance.

PMID- 28501984
TI  - Pediatric Gynecologic Cancers.
AB  - PURPOSE OF REVIEW: Three primary categories of gynecologic cancer are found in
      pediatric and adolescent patients: stromal carcinomas including juvenile
      granulosa cell tumors and Sertoli-Leydig cell tumors, rhabdomyosarcomas arising
      from the vagina and cervix (sarcoma botryoides), and ovarian germ cell tumors
      which comprise a wide range of histologies. These entities are rare and treatment
      approaches have focused on decreasing late effects of chemotherapy treatment.
      Here, we review presentation, histologic classifications, diagnosis, and
      treatment recommendations for pediatric gynecologic cancers. RECENT FINDINGS:
      Event-free and overall survival for these cancers is high, and the goals of
      treatment are minimization of morbidity and preservation of fertility with
      unilateral salpingo-oophorectomies and limited staging. Surveillance of tumor
      markers after surgery is helpful in monitoring for disease progression and
      adjuvant chemotherapy is often reserved for patients at recurrence. Recent
      literature supports avoiding chemotherapy even in high-grade germ cell tumors in
      the pediatric population.

PMID- 28501983
TI  - Understanding the Two Faces of Low-Salt Intake.
AB  - Fierce debate has developed whether low-sodium intake, like high-sodium intake,
      could be associated with adverse outcome. The debate originates in earlier
      epidemiological studies associating high-sodium intake with high blood pressure
      and more recent studies demonstrating a higher cardiovascular event rate with
      both low- and high-sodium intake. This brings into question whether we entirely
      understand the consequences of high- and (very) low-sodium intake for the
      systemic hemodynamics, the kidney function, the vascular wall, the immune system,
      and the brain. Evolutionarily, sodium retention mechanisms in the context of low
      dietary sodium provided a survival advantage and are highly conserved,
      exemplified by the renin-angiotensin system. What is the potential for this
      sodium-retaining mechanism to cause harm? In this paper, we will consider current
      views on how a sodium load is handled, visiting aspects including the effect of
      sodium on the vessel wall, the sympathetic nervous system, the brain renin
      angiotensin system, the skin as "third compartment" coupling to vascular
      endothelial growth factor C, and the kidneys. From these perspectives, several
      mechanisms can be envisioned whereby a low-sodium diet could potentially cause
      harm, including the renin-angiotensin system and the sympathetic nervous system.
      Altogether, the uncertainties preclude a unifying model or practical clinical
      guidance regarding the effects of a low-sodium diet for an individual. There is a
      very strong need for fundamental and translational studies to enhance the
      understanding of the potential adverse consequences of low-salt intake as an
      initial step to facilitate better clinical guidance.

PMID- 28501987
TI  - Effect of glucose and olive oil as potential carbon sources on production of PHAs
      copolymer and tercopolymer by Bacillus cereus FA11.
AB  - In this study, the influence of different physicochemical parameters on the yield
      of polyhydroxyalkanoates (PHAs) produced by Bacillus cereus FA11 is investigated.
      The physicochemical factors include pH, temperature, time, inoculum size and its
      age, agitation speed and composition of the glucose rich peptone deficient (GRPD)
      medium. During two-stage fermentation, B. cereus FA11 produced a significantly
      high (p < 0.05) yield (80.59% w/w) of PHAs copolymer using GRPD medium containing
      glucose (15 g/L) and peptone (2 g/L) at pH 7, 30  degrees C and 150 rpm after 48
      h of incubation. On the other hand, the presence of olive oil (1% v/v) and
      peptone (2 g/L) in the GRPD medium resulted in biosynthesis of tercopolymer
      during two-stage fermentation and the yield of tercopolymer was 60.31% (w/w). The
      purified PHAs was characterized by Fourier transform infrared spectroscopy and
      proton resonance magnetic analysis. Proton resonance magnetic analysis confirmed
      that the tercopolymer was comprised of three different monomeric subunits, i.e.,
      3-hydroxybutyrate, 3-hydroxyvalerate and 6-hydroxyhexanoate.

PMID- 28501988
TI  - Gluteus maximus contraction velocity assessed by tensiomyography improves
      following arthroscopic treatment of femoroacetabular impingement.
AB  - PURPOSE: Muscular impairment, particularly for the gluteus maximus (GM), has been
      observed in femoroacetabular impingement (FAI). The purpose of this study was to
      evaluate the tensiomyographic changes of the GM, rectus femoris (RF) and adductor
      longus (AL) before and after arthroscopic surgery for FAI. It was hypothesized
      that arthroscopic treatment of FAI would improve the preoperative muscular
      impairment. METHODS: All patients undergoing arthroscopic treatment of FAI
      between January and July 2015 were approached for eligibility. Patients included
      had a tensiomyography (TMG) evaluation including maximal displacement (Dm) and
      contraction time (Tc) of these muscles in both lower extremities. TMG values
      between the injured and healthy sides were compared at the preoperative and post
      operative (3, 6 and 12 months after surgery) periods. RESULTS: There were no
      significant differences for the RF and AL, and Dm of the GM for any of the
      comparisons (n.s.). However, GM Tc was significantly lower at 3 (p = 0.016), 6 (p
      = 0.008), and 12 (p = 0.049) months after surgery in the injured side compared to
      preoperatively. GM Tc of the healthy side was significantly lower than the
      injured side at the preoperative period (p = 0.004) and at 3 (p = 0.024) and 6 (p
      = 0.028) months after surgery, but these significant differences were no longer
      observed at 12 months after surgery (n.s.). There was a significant reduction of
      pain in the GM area at 1 year after surgery compared to preoperatively (p <
      0.0001). CONCLUSIONS: Arthroscopic treatment of FAI and the subsequent
      rehabilitation improves contraction velocity of the GM of the injured side.
      Despite Tc is elevated in the GM of the injured compared to the healthy side
      preoperatively and at 3 and 6 months after surgery, differences in Tc between
      both sides are no longer significant at 12 months. Athletes with FAI
      participating in sports with great involvement of GM may benefit from
      arthroscopic treatment and its subsequent rehabilitation. TMG can be used as an
      objective measurement to monitor muscular improvements of the GM after surgery in
      these patients. LEVEL OF EVIDENCE: II.

PMID- 28501990
TI  - Tumor Staging and Grading: A Primer.
AB  - Cancer staging and grading are used to predict the clinical behavior of
      malignancies, establish appropriate therapies, and facilitate exchange of precise
      information between clinicians. The internationally accepted criterion for cancer
      staging, the tumor-node-metastasis (TNM) system, includes: (1) tumor size and
      local growth (T), (2) extent of lymph node metastases (N), and (3) occurrence of
      distant metastases (M). Clinical stage is established before initiation of
      therapy and is determined by physical examination, laboratory findings, and
      imaging studies. Pathologic stage is determined following surgical exploration of
      disease and histologic examination of tissue. The TNM classification system has
      evolved over 70 years to accommodate increasing knowledge about cancer biology.
      Molecular technologies such as genomic and proteomic profiling of tumors could
      eventually be incorporated into the TNM staging system. This chapter describes
      the current TNM system using breast, lung, ovarian, and prostate cancer examples.

PMID- 28501991
TI  - Innovations in Clinical Trial Design in the Era of Molecular Profiling.
AB  - Historically, cancer has been studied, and therapeutic agents have been evaluated
      based on organ site, clinical staging, and histology. The science of molecular
      profiling has expanded our knowledge of cancer at the cellular and molecular
      level such that numerous subtypes are being described based on biomarker
      expression and genetic mutations rather than traditional classifications of the
      disease. Drug development has experienced a concomitant revolution in response to
      this knowledge with many new targeted therapeutic agents becoming available, and
      this has necessitated an evolution in clinical trial design. The traditional,
      large phase II and phase III adjuvant trial models need to be replaced with
      smaller, shorter, and more focused trials. These trials need to be more efficient
      and adaptive in order to quickly assess the efficacy of new agents and develop
      new companion diagnostics. We are now seeing a substantial shift from the
      traditional multiphase trial model to an increase in phase II adjuvant and
      neoadjuvant trials in earlier-stage disease incorporating surrogate endpoints for
      long-term survival to assess efficacy of therapeutic agents in shorter time
      frames. New trial designs have emerged with capabilities to assess more
      efficiently multiple disease types, multiple molecular subtypes, and multiple
      agents simultaneously, and regulatory agencies have responded by outlining new
      pathways for accelerated drug approval that can help bring effective targeted
      therapeutic agents to the clinic more quickly for patients in need.

PMID- 28501989
TI  - Negative control of Candida albicans filamentation-associated gene expression by
      essential protein kinase gene KIN28.
AB  - The fungus Candida albicans can grow as either yeast or filaments, which include
      hyphae and pseudohyphae, depending on environmental conditions. Filamentous
      growth is of particular interest because it is required for biofilm formation and
      for pathogenesis. Environmentally induced filamentous growth is associated with
      expression of filamentation-associated genes, and both filamentous growth and
      associated gene expression depend upon several well-characterized transcription
      factors. Surprisingly, strains with reduced expression of many essential genes
      display filamentous growth under non-inducing conditions-those in which the wild
      type grows as yeast. We found recently that diminished expression of several
      essential protein kinase genes leads to both filamentous cell morphology and
      filamentation-associated gene expression under non-inducing conditions. Reduced
      expression of the essential protein kinase gene CAK1 promoted filamentation
      associated gene expression and biofilm formation in strains that lacked key
      transcriptional activators of these processes, thus indicating that CAK1
      expression is critical for both environmental and genetic control of
      filamentation. In this study, we extend our genetic interaction analysis to a
      second essential protein kinase gene, KIN28. Reduced expression of KIN28 also
      permits filamentation-associated gene expression, though not biofilm formation,
      in the absence of several key transcriptional activators. Our results argue that
      impairment of several essential cellular processes can alter the regulatory
      requirements for filamentation-associated gene expression. Our results also
      indicate that levels of filamentation-associated gene expression are not fully
      predictive of biofilm formation ability.

PMID- 28501992
TI  - Personalized Medicine: Ethical Aspects.
AB  - In our time of genome-based personalized medicine, clinical research and clinical
      medicine are accelerating at a quick pace. Faster and cheaper DNA sequencing and
      protein profiling, microfluidic devices for capturing blood biomarkers,
      nanoparticles for precise drug delivery and enhanced imaging, rapid computational
      analysis of massive data inputs, and other technological wonders coalesce to
      create a kind of Moore's Law for medicine. Needs are obvious, knowledge grows,
      capital becomes available, but these factors are not entirely sufficient to make
      health more achievable. Personalized medicine also requires social acceptability,
      not only for accuracy and efficacy but also because medicine is a moral domain.
      This chapter deals with medical ethics that determine the choices a society makes
      regarding healthcare; and it has not always been a steady, morally correct course
      of progress. Indeed, medical ethics has largely derived from socio-scientific
      calamities in the past. Personalized medicine, with its enhanced capacity to
      access the individuality of illness, must have a continuously evolving feedback
      mechanism-the most important element being the physician-patient relationship
      which is its ethical footing.

PMID- 28501993
TI  - Antibody Validation by Western Blotting.
AB  - Validation of antibodies is an integral part of translational research,
      particularly for biomarker discovery. Assaying the specificity of the reagent
      (antibody) and confirming the identity of the protein biomarker is of critical
      importance prior to implementing any biomarker in clinical studies, and the lack
      of such quality control tests may result in unexpected and/or misleading
      results.Antibody validation is the procedure in which a single antibody is
      thoroughly assayed for sensitivity and specificity. Although a plethora of
      commercial antibodies exist, antibody specificity must be extensively
      demonstrated using diverse complex biological samples, rather than purified
      recombinant proteins, prior to use in clinical translational research. In the
      simplest iteration, antibody specificity is determined by the presence of a
      single band in a complex biological sample, at the expected molecular weight, on
      a Western blot.To date, numerous Western blotting procedures are available, based
      on either manual or automated systems and spanning the spectrum of single blots
      to multiplex blots. X-ray film is still employed in many research laboratories,
      but digital imaging has become a gold standard in immunoblotting. The basic
      principles of Western blotting are (a) separation of protein mixtures by gel
      electrophoresis, (b) transfer of the proteins to a blot, (c) probing the blot for
      a protein or proteins of interest, and (d) subsequent detection of the protein by
      chemiluminescent, fluorescent, or colorimetric methods. This chapter focuses on
      the chemiluminescent detection of proteins using a manual Western blotting system
      and a vacuum-enhanced detection system (SNAP i.d.TM, Millipore).

PMID- 28501994
TI  - Scanning Electron Microscopy Sample Preparation and Imaging.
AB  - Scanning electron microscopes allow us to reach magnifications of 20-130,000* and
      resolve compositional and topographical images with intense detail. These images
      are created by bombarding a sample with electrons in a focused manner to generate
      a black and white image from the electrons that bounce off of the sample. The
      electrons are detected using positively charged detectors. Scanning electron
      microscopy permits three-dimensional imaging of desiccated specimens or wet cells
      and tissues by using variable pressure chambers. SEM ultrastructural analysis and
      intracellular imaging supplement light microscopy for molecular profiling of
      prokaryotes, plants, and mammals. This chapter demonstrates how to prepare and
      image samples that are (a) desiccated and conductive, (b) desiccated and
      nonconductive but coated with an electron conductive film using a gold sputter
      coater, and

PMID- 28501995
TI  - One-Step Preservation and Decalcification of Bony Tissue for Molecular Profiling.
AB  - Bone metastasis from primary cancer sites creates diagnostic and therapeutic
      challenges. Calcified bone is difficult to biopsy due to tissue hardness and
      patient discomfort, thus limiting the frequency and availability of bone/bone
      marrow biopsy material for molecular profiling. In addition, bony tissue must be
      demineralized (decalcified) prior to histomorphologic analysis. Decalcification
      processes rely on three main principles: (a) solubility of calcium salts in an
      acid, such as formic or nitric acid; (b) calcium chelation with
      ethylenediaminetetraacetic acid (EDTA); or (c) ion-exchange resins in a weak
      acid. A major roadblock in molecular profiling of bony tissue has been the lack
      of a suitable demineralization process that preserves histomorphology of
      calcified and soft tissue elements while also preserving phosphoproteins and
      nucleic acids. In this chapter, we describe general issues relevant to specimen
      collection and preservation of osseous tissue for molecular profiling. We provide
      two protocols: (a) one-step preservation of tissue histomorphology and proteins
      and posttranslational modifications, with simultaneous decalcification of bony
      tissue, and (b) ethanol-based tissue processing for TheraLin-fixed bony tissue.

PMID- 28501996
TI  - Application of Hydrogel Nanoparticles for the Capture, Concentration, and
      Preservation of Low-Abundance Biomarkers.
AB  - In the recent years, a lot of emphasis has been placed on the discovery and
      detection of clinically relevant biomarkers. Biomarkers are crucial for the early
      detection of several diseases, and they play an important role in the improvement
      of current treatments, thus reducing patient mortality rate. Because biofluids
      account to 60% of the body mass, they represent a goldmine of significant
      biomarkers. Unfortunately, because of their low concentration in body fluids,
      their lability, and the presence of high abundance proteins (i.e., albumin and
      immunoglobulins), low abundance biomarkers are difficult to detect with mass
      spectrometry or immunoassays. Nanoparticles made of poly(N-isopropylacrylamide)
      (NIPAm) and functionalized with affinity reactive baits allow researchers to
      overcome these physiological barriers and in one single step capture,
      concentrate, and preserve labile biomarkers in complex body fluids (i.e. urine,
      blood, sweat, CSF). Although hydrogel nanoparticles have been largely studied and
      used as a drug delivery tool, our application focuses on their capturing
      abilities instead of the releasing of specific drug molecules. Once the
      functionalized nanoparticles are incubated with a biological fluid, small
      biomarkers are captured by the affinity baits while unwanted high abundance
      analytes are excluded. The potentially relevant biomarkers are then concentrated
      into small volumes. The concentration factor (up to 10,000-fold) successfully
      enhances the detection sensitivity of mass spectrometry and immunoassays allowing
      the detection of previously invisible proteins.

PMID- 28501997
TI  - Using Laser Capture Microdissection to Isolate Cortical Laminae in Nonhuman
      Primate Brain.
AB  - Laser capture microdissection (LCM) is a technique that allows procurement of an
      enriched cell population from a heterogeneous tissue sample under direct
      microscopic visualization. Fundamentally, laser capture microdissection consists
      of three main steps: (1) visualizing the desired cell population by microscopy,
      (2) melting a thermolabile polymer onto the desired cell populations using
      infrared laser energy to form a polymer-cell composite (capture method) or
      photovolatizing a region of tissue using ultraviolet laser energy (cutting
      method), and (3) removing the desired cell population from the heterogeneous
      tissue. In this chapter, we discuss the infrared capture method only. LCM
      technology is compatible with a wide range of downstream applications such as
      mass spectrometry, DNA genotyping and RNA transcript profiling, cDNA library
      generation, proteomics discovery, and signal pathway mapping. This chapter
      profiles the ArcturusXTTM laser capture microdissection instrument, using
      isolation of specific cortical lamina from nonhuman primate brain regions, and
      sample preparation methods for downstream proteomic applications.

PMID- 28501998
TI  - Western Blot Techniques.
AB  - The Western blot is an important laboratory technique that allows for specific
      identification and characterization of proteins. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE)-separated proteins are
      electophoretically transferred to a polyvinylidene fluoride (PVDF) membrane which
      is then incubated with specific antibodies, then developed to show the protein of
      interest. Here, we describe the transfer and detection of Outer surface protein A
      (OspA), a protein only found on the surface of Borrelia burgdorferi, the bacteria
      responsible for Lyme disease.

PMID- 28501999
TI  - ELISA for Monitoring Nerve Growth Factor.
AB  - Nerve growth factor (NGF), a neurotrophin critical to neuronal viability, has
      become a popular research focus for the treatment of neurodegenerative diseases.
      Enzyme-linked immunosorbent assays (ELISA) allow the quantification of cellular
      proteins, such as NGF, secreted into conditioned culture media. However, off-the
      shelf reagents and kit components may require optimization depending on the
      specific specimens and/or antibodies that will be utilized with the ELISA assay.
      Herein we describe a protocol for developing a sandwich ELISA, incorporating NGF
      specific primary and secondary antibodies capable of detecting NGF at
      concentrations as low as 10 pg/mL.

PMID- 28502000
TI  - Reverse Phase Protein Microarrays.
AB  - While genes and RNA encode information about cellular status, proteins are
      considered the engine of the cellular machine, as they are the effective elements
      that drive all cellular functions including proliferation, migration,
      differentiation, and apoptosis. Consequently, investigations of the cellular
      protein network are considered a fundamental tool for understanding cellular
      functions.Alteration of the cellular homeostasis driven by elaborate intra- and
      extracellular interactions has become one of the most studied fields in the era
      of personalized medicine and targeted therapy. Increasing interest has been
      focused on developing and improving proteomic technologies that are suitable for
      analysis of clinical samples. In this context, reverse-phase protein microarrays
      (RPPA) is a sensitive, quantitative, high-throughput immunoassay for protein
      analyses of tissue samples, cells, and body fluids.RPPA is well suited for broad
      proteomic profiling and is capable of capturing protein activation as well as
      biochemical reactions such as phosphorylation, glycosylation, ubiquitination,
      protein cleavage, and conformational alterations across hundreds of samples using
      a limited amount of biological material. For these reasons, RPPA represents a
      valid tool for protein analyses and generates data that help elucidate the
      functional signaling architecture through protein-protein interaction and protein
      activation mapping for the identification of critical nodes for individualized or
      combinatorial targeted therapy.

PMID- 28502001
TI  - Clustering and Network Analysis of Reverse Phase Protein Array Data.
AB  - Molecular profiling of proteins and phosphoproteins using a reverse phase protein
      array (RPPA) platform, with a panel of target-specific antibodies, enables the
      parallel, quantitative proteomic analysis of many biological samples in a
      microarray format. Hence, RPPA analysis can generate a high volume of
      multidimensional data that must be effectively interrogated and interpreted. A
      range of computational techniques for data mining can be applied to detect and
      explore data structure and to form functional predictions from large datasets.
      Here, two approaches for the computational analysis of RPPA data are detailed:
      the identification of similar patterns of protein expression by hierarchical
      cluster analysis and the modeling of protein interactions and signaling
      relationships by network analysis. The protocols use freely available, cross
      platform software, are easy to implement, and do not require any programming
      expertise. Serving as data-driven starting points for further in-depth analysis,
      validation, and biological experimentation, these and related bioinformatic
      approaches can accelerate the functional interpretation of RPPA data.

PMID- 28502002
TI  - PCR: Identification of Genetic Polymorphisms.
AB  - Polymerase chain reaction (PCR) enables the amplification of a specific sequence
      of deoxyribonucleic acid (DNA) through the process of three main steps: template
      DNA denaturation, annealing of the primers to complementary sequences, and primer
      extension to synthesize DNA strands. By using this method, the target sequence
      will be copied and amplified at an exponential rate. PCR provides a qualitative
      method for identifying DNA from fresh or dried cells/body fluids, formalin-fixed
      archival tissue specimens, and ancient specimens.Herein we describe basic
      information for performing successful PCR experiments using the amplification of
      a human Alu insertion on the PV92 gene locus on chromosome 16 as an example
      method.

PMID- 28502004
TI  - Somatic DNA Mutation Analysis.
AB  - Somatic mutations in patient tumor DNA samples can be readily detected based on
      mass spectrometry. The MassARRAY system is a high-throughput matrix-assisted
      laser desorption time-of-flight (MALDI) mass spectrometer for detection of
      nucleic acids. The technique is based on single-nucleotide base extension. A
      series of PCR assays amplify specific DNA regions of interest harboring
      mutations. A third primer is then introduced into the reaction which corresponds
      to the DNA template immediately in front of the mutation site. A final round of
      PCR is then performed using mass-modified nucleotides. These nucleotides are
      designed so that no additional bases can be added to the extension primer
      (terminating bases) after a single-base extension and are mass modified to
      exaggerate mass differences between nucleotides allowing easier identification by
      mass spectrometry.The sequences of the extension primer and possible extension
      products (wild type and mutations) are known; therefore, it is possible to
      calculate their mass. The mass spectrometer can identify the mass peaks for each
      assay and identify those with mutations (multiple peaks). The technique was
      originally designed to screen multiple single-nucleotide polymorphisms (SNPs) in
      a large number of specimens. A SNP in the coding region of DNA that alters the
      gene and subsequent protein expression is considered a mutation. Mutations often
      occur in genes whose protein product is in a key signaling pathway and/or drug
      target. Rationale treatment options can be designed based upon the presence or
      absence of these mutations. In this chapter, we describe the process for
      detection of somatic mutations in DNA extracted from formalin-fixed paraffin
      embedded (FFPE) material.

PMID- 28502003
TI  - Microsatellite Analysis for Identification of Individuals Using Bone from the
      Extinct Steller's Sea Cow (Hydrodamalis gigas).
AB  - Microsatellite DNA can provide more detailed population genetic information than
      mitochondrial DNA which is normally used to research ancient bone. The methods
      detailed in this chapter can be utilized for any type of bone. However, for this
      example, four microsatellite loci were isolated from Steller's sea cow
      (Hydrodamalis gigas) using published primers for manatee and dugong
      microsatellites. The primers DduC05 (Broderick et al., Mol Ecol Notes 6:1275
      1277, 2007), Tmakb60, TmaSC5 (Pause et al., Mol Ecol Notes 6: 1073-1076, 2007),
      and TmaE11 (Garcia-Rodriguez et al., Mol Ecol 12:2161-2163, 2000) all
      successfully amplified microsatellites from H. gigas. The DNA samples were from
      bone collected on Bering or St. Lawrence Islands. DNA was analyzed using primers
      with the fluorescent label FAM-6. Sequenced alleles were then used to indicate a
      difference in the number of repeats and thus a difference in individuals. This is
      the first time that H. gigas microsatellite loci have been isolated. These
      techniques for ancient bone microsatellite analysis allow an estimate of
      population size for a newly discovered St. Lawrence Island sea cow population.

PMID- 28502005
TI  - Optimization of Immunostaining for Prospective Image Analysis.
AB  - Biomarker discovery is a crucial part of the fast developing field of
      personalized medicine. Antibody-based techniques including immunostaining of
      tissue samples are widely used for biomarker evaluation in preclinical and
      clinical studies. When used in conjunction with robust image analysis methods, it
      provides a powerful means to assess biomarker modulation, toxicity, and patient
      response to targeted agents. Here, we describe the optimization of
      immunofluorescent (IF) staining protocols and a sample IF multiplex protocol
      suitable for colocalization image analysis.

PMID- 28502006
TI  - Fluorescence In Situ Hybridization of Cells, Chromosomes, and Formalin-Fixed
      Paraffin-Embedded Tissues.
AB  - Fluorescence in situ hybridization (FISH) with DNA probes allows the
      visualization of gene copy number and localization of specific DNA targets with
      fluorescence microscopy. Cells in culture, metaphase chromosomes, and tissue
      sections are fixed and prepared on glass slides. Both the DNA in the cells and
      fluorescently labeled probe are denatured, and the labeled probe is allowed to
      hybridize to the cellular DNA. The slides are washed, counterstained, and viewed
      via fluorescence microscopy. We describe the basic method for preparing slides
      and probes for studies involving DNA copy number changes and structural
      chromosome rearrangements in formalin-fixed paraffin-embedded (FFPE) tissue
      sections and cell culture preparations.

PMID- 28502007
TI  - High-Resolution Image Stitching as a Tool to Assess Tissue-Level Protein
      Distribution and Localization.
AB  - High-resolution microscopy has traditionally come at the expense of field of
      view, resulting in suboptimal interpretation of protein distribution throughout
      large or complex samples. Likewise, a low-resolution microscopic approach
      inhibits the ability of researchers to precisely localize proteins of interest at
      the subcellular level. Until recently, the ability to combine the strengths of
      these approaches was limited and technically impractical for most laboratories to
      implement. Continued advances in microscope automation, sophisticated software
      applications, and modern workstations have enabled expansion of such
      combinatorial approaches to researchers outside computationally focused fields.
      Through image stitching, researchers can acquire large field-of-view,
      multidimensional datasets, at the diffraction limit of high-numerical aperture
      objectives to effectively map protein distribution in large samples with high
      precision. Here, we outline a protocol for acquisition of such datasets with the
      purpose of introducing inexperienced researchers to the methodology of large
      image stitching using the widely available technology of laser point-scanning
      confocal microscopy in combination with basic microscope automation and freely
      available software for post-acquisition processing.

PMID- 28502008
TI  - Mass Spectrometry-Based Biomarker Discovery.
AB  - The discovery of candidate biomarkers within the entire proteome is one of the
      most important and challenging goals in proteomic research. Mass spectrometry
      based proteomics is a modern and promising technology for semiquantitative and
      qualitative assessment of proteins, enabling protein sequencing and
      identification with exquisite accuracy and sensitivity. For mass spectrometry
      analysis, protein extractions from tissues or body fluids and subsequent protein
      fractionation represent an important and unavoidable step in the workflow for
      biomarker discovery. Following extraction of proteins, the protein mixture must
      be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The
      aim of our chapter is to provide comprehensible and practical lab procedures for
      sample digestion, protein fractionation, and subsequent mass spectrometry
      analysis.

PMID- 28502009
TI  - Quantitative Mass Spectrometry by Isotope Dilution and Multiple Reaction
      Monitoring (MRM).
AB  - Selected reaction monitoring (SRM) is used in molecular profiling to detect and
      quantify specific known proteins in complex mixtures. Using isotope dilution
      (Barnidge et al., Anal Chem 75(3):445-451, 2003) methodologies, peptides can be
      quantified without the need for an antibody-based method. Selected reaction
      monitoring assays employ electrospray ionization mass spectrometry (ESI-MS)
      followed by two stages of mass selection: a first stage where the mass of the
      peptide ion is selected and, after fragmentation by collision-induced
      dissociation (CID), a second stage (tandem MS) where either a single (e.g., SRM)
      or multiple (multiple reaction monitoring, MRM) specific peptide fragment ions
      are transmitted for detection. The MRM experiment is accomplished by specifying
      the parent masses of the selected endogenous and isotope-labeled peptides for
      MS/MS fragmentation and then monitoring fragment ions of interest, using their
      intensities/abundances and relative ratios to quantify the parent protein of
      interest. In this example protocol, we will utilize isotope dilution MRM-MS to
      quantify in absolute terms the total levels of the protein of interest, ataxia
      telangiectasia mutated (ATM) serine/threonine protein kinase. Ataxia
      telangiectasia mutated (ATM) phosphorylates several key proteins that initiate
      activation of the DNA damage checkpoint leading to cell cycle arrest.

PMID- 28502010
TI  - LC-Mass Spectrometry for Metabolomics.
AB  - The field of metabolomics is greatly being refined by the addition of new
      technologies. LC-MS has allowed researchers to explore additional metabolites
      which were not originally captured through GC-MS. Through the customizability of
      the LC columns and mass spectrometer, it is now easier to tailor the instrument
      to your research needs. Herein, we describe a protocol for sample preparation and
      data acquisition for a global metabolomic analysis of tissues or feces.

PMID- 28502011
TI  - Metabolomic Bioinformatic Analysis.
AB  - Metabolomics allows for the investigation of the small molecules found within
      living systems. Based on the design of the experiments, it is not uncommon for
      these analyses to include matrices of thousands of variables. In order to handle
      such large datasets, many have turned to multivariate statistical analyses to
      analyze and understand their data. Herein, we present protocols for using R to
      analyze metabolomic data using some of the more common multivariate statistical
      techniques.

PMID- 28502012
TI  - Stable Isotope Quantitative N-Glycan Analysis by Liquid Separation Techniques and
      Mass Spectrometry.
AB  - Liquid phase separation analysis and subsequent quantitation remains a
      challenging task for protein-derived oligosaccharides due to their inherent
      structural complexity and diversity. Incomplete resolution or co-detection of
      multiple glycan species complicates peak area-based quantitation and associated
      statistical analysis when optical detection methods are used. The approach
      outlined herein describes the utilization of stable isotope variants of commonly
      used fluorescent tags that allow for mass-based glycan identification and
      relative quantitation following separation by liquid chromatography (LC) or
      capillary electrophoresis (CE). Comparability assessment of glycoprotein-derived
      oligosaccharides is performed by derivatization with commercially available
      isotope variants of 2-aminobenzoic acid or aniline and analysis by LC- and CE
      mass spectrometry. Quantitative information is attained from the extracted ion
      chromatogram/electropherogram ratios generated from the light and heavy isotope
      clusters.

PMID- 28502013
TI  - Grant Writing Tips for Translational Research.
AB  - All investigators face the same challenge-the highly competitive nature of the
      grant review process. Innovation alone is not enough to ensure grant-supported
      funding. Applied clinical research requires a diverse, collaborative team of
      investigators with specialized skills, a supportive clinical research
      environment, and access to clinical material. Additionally, the lack of animal
      models for many diseases and ethical limitations prevent direct mechanistic
      experiments that are possible using in vitro systems or animal models. Therefore,
      specific granting mechanisms and program initiatives target translational
      research studies. This chapter provides grant writing tips and lists resources
      that may prove helpful for new investigators seeking research funding in support
      of translational research, biobanking, and research utilizing molecular
      biomarkers.

PMID- 28502014
TI  - Inventions and Patents: A Practical Tutorial.
AB  - Patents are designed to protect and encourage creativity and innovation.
      Patenting a biomedical discovery can be a requirement before a pharmaceutical
      company or biotech entity will invest in the lengthy and capital-intensive drug
      development and clinical trials necessary to achieve patient benefit. Although
      scientists and clinicians are well versed in research publication requirements,
      patent descriptions and claims are formatted in a manner quite different from a
      research paper. Patents require (a) a series of logical statements clearly
      delineating the boundaries of the novel aspects of the invention and (b)
      sufficient disclosure of the invention so that it can be reproduced by others.
      Patents are granted only for inventions that meet three conditions: novelty, non
      obviousness, and usefulness. Recent changes to US patent law limit the scope of
      patentable material. Products of nature such as nucleic acids and proteins, or
      steps used to observe natural events, are no longer patent eligible. This chapter
      provides basic guidelines and definitions for inventions, inventorship, and
      patent filing which are summarized using a question and answer format.

PMID- 28502015
TI  - Product Development and Commercialization of Diagnostic or Life Science Products
      for Scientists and Researchers.
AB  - Commercializing a diagnostic or life science product often encompasses different
      goals than that of research and grant funding. There are several necessary steps,
      and a strategy needs to be well defined in order to be successful. Product
      development requires input from and between various groups within a company and,
      for academia, outside entities. The product development stakeholder
      groups/entities are research, marketing, development, regulatory, manufacturing,
      clinical, safety/efficacy, and quality. After initial research and development,
      much of the work in product development can be outsourced or jointly created
      using public-private partnerships. This chapter serves as an overview of the
      product development process and provides a guide to best define a product
      strategy.

PMID- 28502016
TI  - Correlation between in vitro and in vivo antimalarial activity of compounds using
      CQ-sensitive and CQ-resistant strains of Plasmodium falciparum and CQ-resistant
      strain of P. yoelii.
AB  - Present efforts have been made to establish a correlation between in vitro and in
      vivo antimalarial activity using MIC, IC50 and IC90 values against CQ-sensitive
      (3D7) and CQ-resistant (K1) strains of Plasmodium falciparum and in vivo activity
      against Plasmodium yoelii. The method of discriminant function analysis (DFA) was
      applied to analyze the data. It was observed that in vitro IC90 values against
      both 3D7 and K1 strains (p < 0.001) have strong correlation with in vivo curative
      activity. The respective IC50 and IC90 values of compounds, which cured mice
      (i.e., animals did not show recrudescence of parasitemia even after 60 days
      posttreatment), ranged between 3 and 14 nM and 14 and 186 nM against 3D7 and
      between 9 and 65 nM and 24 and 359 nM against the K1 strain of P. falciparum.
      Whereas the IC50 and IC90 values of compounds which exhibited in vivo suppressive
      activity in mice ranged between 10 and 307 nm and 61 and >965 nM, respectively,
      against 3D7 and 75 and >806 nm and 241 and >1232 nM against the K1 strain of P.
      falciparum. The findings suggest that IC90 values against both 3D7 and K1 strains
      (p < 0.02) are the main contributors for the prediction of in vivo curative
      activity of a new molecule. Apart from this, a reasonable correlation between MIC
      and IC50 values of compounds has also been established.

PMID- 28502017
TI  - Comparative analysis of immune effects in mice model: Clonorchis sinensis
      cysteine protease generated from recombinant Escherichia coli and Bacillus
      subtilis spores.
AB  - Clonorchiasis remains a nonnegligible public health problem in endemic areas.
      Cysteine protease of Clonorchis sinensis (CsCP) plays indispensable roles in the
      parasitic physiology and pathology, and has been exploited as a promising drug
      and vaccine candidate. In recent years, development of spore-based vaccines
      against multiple pathogens has attracted many investigators' interest. In
      previous studies, the recombinant Escherichia coli (BL21) and Bacillus subtilis
      spores expressing CsCP have been successfully constructed, respectively. In this
      study, the immune effects of CsCP protein purified from recombinant BL21 (rCsCP)
      and B. subtilis spores presenting CsCP (B.s-CsCP) in Balb/c mice model were
      conducted with comparative analysis. Levels of specific IgG, IgG1 and IgG2a were
      significantly increased in sera from both rCsCP and B.s-CsCP intraperitoneally
      immunized mice. Additionally, recombinant spores expressing abundant fusion CsCP
      (0.03125 pg/spore) could strongly enhance the immunogenicity of CsCP with
      significantly higher levels of IgG and isotypes. Compared with rCsCP alone,
      intraperitoneal administration of mice with spores expressing CsCP achieved a
      better effect of fighting against C. sinensis infection by slowing down the
      process of fibrosis. Our results demonstrated that a combination of Th1/Th2
      immune responses could be elicited by rCsCP, while spores displaying CsCP
      prominently induced Th1-biased specific immune responses, and the complex
      cytokine network maybe mediates protective immune responses against C. sinensis.
      This work further confirmed that the usage of B. subtilis spores displaying CsCP
      is an effective way to against C. sinensis.

PMID- 28502018
TI  - Evolutionary processes in populations of Cryptosporidium inferred from gp60
      sequence data.
AB  - Cryptosporidiosis is one of the most common human infectious diseases globally.
      The gp60 gene has been adopted as a key marker for molecular epidemiological
      investigations into this protozoan disease because of the capability to
      characterize genotypes and detect variants within Cryptosporidium species
      infecting humans. However, we know relatively little about the potential spatial
      and temporal variation in population demography that can be inferred from this
      gene beyond that it is recognized to be under selective pressure. Here, we
      analyzed the genetic variation in time and space within two putative populations
      of Cryptosporidium in New Zealand to infer the processes behind the patterns of
      sequence polymorphism. Analyses using Tajima's D, Fu, and Li's D* and F* tests
      show significant departures from neutrality in some populations and indicate the
      selective maintenance of alleles within some populations. Demographic analyses
      showed distortions in the pattern of the genetic variability caused by high
      recombination rates and population expansion, which was observed in case
      notification data. Our results showed that processes acting on populations that
      have similar effects can be distinguished from one another and multiple processes
      can be detected acting at the same time. These results are significant for
      prediction of the parasite dynamics and potential mechanisms of long-term changes
      in the risk of cryptosporidiosis in humans.

PMID- 28502019
TI  - A revision of the genus Aphalloides (Digenea: Cryptogonimidae), parasites of
      European brackish water fishes.
AB  - Trematodes of the genus Aphalloides Dollfus, Chabaud & Golvan, 1957 reach
      maturity in their second intermediate host, small fishes of the family
      Gobionellidae, genera Pomatoschistus and Knipowitschia. Two morphologically
      similar species have been described from European waters: Aphalloides coelomicola
      Dollfus et al., 1957 in the Mediterranean Sea (including the brackish Black Sea
      region) and Aphalloides timmi Reimer, 1970 in the Baltic Sea. There was no
      difference in morphology and morphometry for specimens corresponding to A.
      coelomicola and A. timmi and examination of the 28S rDNA sequence confirmed the
      similarity. Based on these results, these two species are synonymized and A.
      coelomicola redescribed.

PMID- 28502020
TI  - Biogeochemical zonation of sulfur during the discharge of groundwater to lake in
      desert plateau (Dakebo Lake, NW China).
AB  - As one of the important elements of controlling the redox system within the
      hyporheic and hypolentic zone, sulfur is involved in a series of complex
      biogeochemical processes such as carbon cycle, water acidification, formation of
      iron and manganese minerals, redox processes of trace metal elements and a series
      of important ecological processes. Previous studies on biogeochemistry of the
      hyporheic and hypolentic zones mostly concentrated on nutrients of nitrogen and
      phosphorus, heavy metals and other pollutants. Systematic study of biogeochemical
      behavior of sulfur and its main controlling factors within the lake hypolentic
      zone is very urgent and important. In this paper, a typical desert plateau lake,
      Dakebo Lake in northwestern China, was taken for example within which redox
      zonation and biogeochemical characteristics of sulfur affected by hydrodynamic
      conditions were studied based on not only traditional hydrochemical analysis, but
      also environmental isotope evidence. In the lake hypolentic zone of the study
      area, due to the different hydrodynamic conditions, vertical profile of sulfur
      species and environmental parameters differ at the two sites of the lake (western
      side and center). Reduction of sulfate, deposition and oxidation of sulfide,
      dissolution and precipitation of sulfur-bearing minerals occurred are responded
      well to Eh, dissolved oxygen, pH, organic carbon and microorganism according to
      which the lake hypolentic zone can be divided into reduced zone containing H2S,
      reduced zone containing no H2S, transition zone and oxidized zone. The results of
      this study provide valuable insights for understanding sulfur conversion
      processes and sulfur biogeochemical zonation within a lake hypolentic zone in an
      extreme plateau arid environment and for protecting the lake-wetland ecosystem in
      arid and semiarid regions.

PMID- 28502022
TI  - Is postural tachycardia syndrome in the head or in the heart? And other updates
      on recent autonomic research.

PMID- 28502021
TI  - The visual and haptic contributions to hand perception.
AB  - Previous research has found that the perception of our hands is distorted. The
      characteristics of this distortion are an overestimation of hand width and an
      underestimation of finger length. The present study examined the role that
      different sensory modalities (vision and/or haptics) play in the perception of
      our hands. Participants pointed to their concealed hand in one of three groups:
      Vision+Haptics, Vision-only, or Haptics-only. Participants in the Vision+Haptics
      group had vision (non-informative) of the experimental setup and of the pointing
      hand, but no vision of the hand being estimated. They also experienced haptic
      feedback as the palm of the hand was in contact with the undersurface of a
      tabletop, where the estimations were made. Participants in the Vision-only group,
      instead of placing the hand to be estimated underneath the tabletop, they placed
      it behind their backs. Participants in this group were asked to imagine as if the
      hand was under the table when making their estimations. In the Haptics-only
      group, participants completed the task with the hand underneath the tabletop (as
      in the Vision+Haptics group) but did so while wearing a blindfold (no vision).
      All participants estimated the position of ten landmarks on the hand: the
      fingertip and the metacarpophalangeal joint of each digit. Hand maps were
      constructed using a 3D motion capture system. Participants in the Haptics-only
      group produced the most accurate hand maps. We discuss the possibility that
      vision interferes with somatosensory processing.

PMID- 28502023
TI  - Sources of Care for Alcohol and Other Drug Problems: The Role of the African
      American Church.
AB  - African Americans experience significant disparities in treatment access,
      retention, and quality of care for alcohol and drug use (AOD) problems. Religious
      congregations, often the first point of contact for help with AOD problems, can
      play an integral role in improving access to treatment. However, little is known
      about the role of African American churches in addressing AOD problems. We
      administered a survey to a faith-based collaborative of 169 African American
      churches in Los Angeles to examine how AOD problems are identified in
      congregations, the types of support provided, barriers to providing treatment
      referrals, and factors associated with the provision of treatment referrals.
      Seventy-one percent of churches reported caring often for individuals with AOD
      problems. AOD problems came to the attention of congregations most commonly via a
      concerned family member (55%) and less frequently through individuals with AOD
      problems directly approaching clergy (30%). In addition to providing spiritual
      support, a substantial proportion of churches reported linking individuals to AOD
      services through referrals (62%) and consultation with providers (48%). Barriers
      to providing treatment referrals included lack of affordable programs (50%),
      stigma (50%), lack of effective treatments (45%), and insufficient resources or
      staff (45%). The likelihood of providing treatment referrals was greater among
      mid-sized versus smaller-size congregations (OR 3.43; p < .05) and among
      congregations with clergy that had attended seminary (OR 3.93; p < .05). Knowing
      how to effectively coordinate informal sources of care provided by African
      American churches with the formal service sector could make a significant impact
      on AOD treatment disparities.

PMID- 28502024
TI  - The Relationship Between Religious Beliefs and Quality of Life Among Patients
      With Multiple Sclerosis.
AB  - Patients with chronic diseases, such as multiple sclerosis (MS), are prone to
      emotional distresses and reduction in life quality more than others. This study
      aimed to assess the relationship between religious beliefs and quality of life
      among patients with MS. In this study, 145 MS patients completed 36-Item Short
      Form Health Survey (SF-36) and the Duke University Religion Index (DUREL)
      questionnaires. The results indicated that unorganized religious activities were
      significantly associated with marital status and education level. Besides,
      internal religion was positively correlated to mental health. However, religious
      variables were not effective prognostic factors in physical and mental quality of
      life. Overall, further studies have to be conducted to determine the role of
      religion in quality of life of MS patients with different religious backgrounds.

PMID- 28502025
TI  - Mindfulness in Salah Prayer and its Association with Mental Health.
AB  - Plethora of researches has been carried out for the last many decades and has
      identified relationship between mental health and religious convictions; in
      particular, range of religious practices has been found instrumental in the
      promotion of mental health. The aim of this paper is to find out association
      between mindfulness in Salah (prayer) and mental health of individuals who
      identify themselves with Islam and to examine the mental health of those Muslims
      who offer Salah prayer with mindfulness and those who offer without mindfulness.
      A total of 174 participants with mean age of 21.57 including 62% males and
      females 38% were selected through convenient sampling. RAND Mental Health
      Inventory was used to measure mental health and other three variables; three self
      reported measures were constructed. They included Islamic religious education
      scale, Salah education scale and mindfulness in Salah scale. Psychometric
      properties for all scales were established. The findings indicated that mean on
      mindfulness and mental health was significantly higher for those who were
      offering Salah (prayer) regularly (p < 0.01) as compared with those who were not
      offering it regularly. Moreover, those who were offering Salah (prayer) with
      mindfulness had also significantly higher mean for mental health (p < 0.01) as
      compared with those who were offering it without mindfulness. Religious
      education, Salah education and mindfulness were able to account for 13% of the
      variance in mental health (p < 0.01). Of note two of the measures included Salah
      education and mindfulness made a significant contribution in the prediction of
      mental health (p < 0.01). The present study indicated that individuals who offer
      prayer regularly and with mindfulness have better mental health as compared with
      those who don't offer it regularly and with mindfulness. The findings of this
      study urge to spread awareness regarding offering prayer regularly with
      mindfulness for the better outcome of mental health in people.

PMID- 28502027
TI  - Assessing the Actual Clinical Effectiveness of Metabolic/Bariatric Surgery for
      the Type 2 Diabetes Therapy.

PMID- 28502026
TI  - Dentin remineralizing ability and enhanced antibacterial activity of strontium
      and hydroxyl ion co-releasing radiopaque hydroxyapatite cement.
AB  - Dental caries is an infection of the mineralized tooth structures that advances
      when acid secreted by bacterial action on dietary carbohydrates diffuses and
      dissolves the tooth mineral leading to demineralization. During treatment,
      clinicians often remove only the superficial infected tooth structures and retain
      a part of affected carious dentin to prevent excessive dentin loss and pulp
      exposure. Calcium hydroxide is used to treat the affected dentin because it is
      alkaline, induces pulp-dentin remineralization and decreases bacterial infection.
      Presence of strontium ions has also been reported to exhibit anticariogenic
      activity, and promote enamel and dentin remineralization. The objective of the
      present study was to develop novel hydroxyapatite cement from tetracalcium
      phosphate which gradually releases hydroxyl and strontium ions to exhibit
      antibacterial activity. Its potential to remineralize the dentin sections
      collected from extracted human molar tooth was studied in detail. The pH of all
      the experimental cements exhibited a gradual increase to ~10.5 in 10 days with
      10% strontium substituted tetracalcium phosphate cement (10SC) showing the
      highest pH value which was sustained for 6 weeks. 10SC showed better
      antibacterial property against S. aureus and E. coli at the end of 1 week
      compared to other cements studied. It also exhibited the highest radiopacity
      equivalent to 4.8 mm of Al standard. 10SC treated dentin section showed better
      remineralization ability and highest elastic modulus. We can conclude that the
      hydroxyl and strontium ions releasing tetracalcium phosphate cement exhibits good
      antibacterial property, radiopacity and has the potential to encourage dentin
      remineralization.

PMID- 28502028
TI  - Hypoglycemia Following Bariatric Surgery: Our 31-Year Experience.
AB  - PURPOSE: The purposes of this study are to identify the cumulative incidence of
      post-bariatric surgery hypoglycemia (PBSH), describe its symptomatology, and
      characterize treatment patterns at a large academic institution. MATERIALS AND
      METHODS: All patients who underwent bariatric surgery at a single institution
      from 1985 to 2015 were identified using a clinical database, administrative
      billing data identified patients who were treated for hypoglycemia, and chart
      reviews were performed to make a diagnosis of PBSH based on Whipple's triad. PBSH
      cases were reviewed including patient diabetes history, symptomatology, and
      treatment measures. Univariate analyses were performed to identify correlations
      based on symptomatology, laboratory values, and treatments utilized. RESULTS:
      Ninety (2.6%) of 3487 patients were diagnosed with PBSH with preoperative median
      age of 43 years, mean BMI of 50.0 kg/m2, and median glycated hemoglobin of 6.0%.
      Median time-to-first hypoglycemic event was 40.6 months. No factors were
      identified which predict symptom severity or resolution. The 24 (27%) patients
      who received pharmacotherapy to treat hypoglycemia were younger, had lower nadir
      blood glucose levels, and more frequent symptoms. Sixty-nine (79%) cases
      eventually resolved. CONCLUSIONS: PBSH onset and severity are highly variable.
      Successful management of these patients can prove difficult and should include
      dietary therapy, the selective use of pharmacotherapy and surgery, and the use of
      a multidisciplinary team including bariatric surgeons and endocrinologists.

PMID- 28502029
TI  - A Longitudinal Analysis of Short-Term Costs and Outcomes in a Regionalized Center
      of Excellence Bariatric Care System.
AB  - BACKGROUND: Evaluating how morbidity and costs evolve for new bariatric centers
      is vital to understanding the expected length of time required to reach optimal
      outcomes and cost efficiencies. Accordingly, the objective of this study was to
      evaluate how morbidity and costs changed longitudinally during the first 5 years
      of a regionalized center of excellence system. METHODS: This was a longitudinal
      analysis of the first 5 years of a bariatric center of excellence system. The
      main outcomes of interest were all-cause morbidity and cost for the index
      admission. Predictors of interest included patient demographics, comorbidities,
      annual hospital and surgeon volume, fellowship teaching center status, and year
      of procedure. Hierarchical regression models were used to determine predictors of
      morbidity and costs. RESULTS: Procedures done in 2012 (OR 0.65, 95%CI 0.52-0.79;
      p < 0.001), 2013 (OR 0.63, 95%CI 0.51-0.78; p < 0.001), and 2014 (OR 0.53, 95%CI
      0.43-0.65; p < 0.001) all conferred a significantly lower odds of morbidity when
      compared to the initial 2009/2010 years. Surgeon volume was associated with a
      decreased odds of morbidity as for each increase in 25 bariatric cases per year
      the odds of all-cause morbidity was 0.94 lower (95%CI 0.88-1.00; p = 0.04). There
      was no significant variation at the hospital or surgeon level in perioperative
      outcomes. CONCLUSION: This study determined that volume was important even for
      high resource, fellowship-trained surgeons. It also found a decrease in morbidity
      over time for new centers. Lastly, there was little variation in outcomes across
      hospitals and surgeons suggesting that strict accreditation standards can help to
      ensure high quality across hospital sites.

PMID- 28502030
TI  - Co-occurrence of type I CALR and two MPL mutations in patient with primary
      myelofibrosis.

PMID- 28502031
TI  - Vitamin D and plasma cell dyscrasias: reviewing the significance.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell
      disorder and precursor disease to multiple myeloma and other related cancers.
      While MGUS is considered a benign disorder, with a low risk of disease
      progression, patients have altered bone microarchitecture and an increased risk
      of bone fracture. In addition, alterations in immune function are regularly found
      to correlate with disease activity. Vitamin D, an important hormone for bone and
      immune health, is commonly deficient in multiple myeloma patients. However,
      vitamin D deficiency is also prevalent in the general population. The purpose of
      this review is to highlight the current understanding of vitamin D in health and
      disease and to parallel this with a review of the abnormalities found in plasma
      cell dyscrasias. While some consensus statements have advocated for vitamin D
      testing and routine supplementation in MGUS, there is no clear standard of care
      approach and clinical practice patterns vary. Further research is needed to
      better understand how vitamin D influences outcomes in MGUS patients.

PMID- 28502033
TI  - A reflection on today's environment for child and adolescent psychiatric
      research. The continuous march for science of European Child + Adolescent
      Psychiatry.

PMID- 28502032
TI  - Circulating markers of bone turnover.
AB  - Renal osteodystrophy is a feature of chronic kidney disease (CKD), with
      increasing prevalence as CKD progresses. This bone disease is responsible for
      major morbidity, including fractures, and a deterioration in the quality of life
      and its sequelae. Circulating biomarkers of renal osteodystrophy typically
      indicate bone turnover, but not other features of bone, like bone volume,
      mineralization, quality or strength. Bone turnover can be considered to be
      primarily a reflection of bone cell activity, in particular that of osteoblasts
      and osteoclasts. Since current treatments for bone disease usually target
      cellular activity, biomarkers are considered to be able to contribute to the
      decision-making for treatment and its follow-up. In CKD, one has to consider the
      impact of a diminished clearance of biomarkers or their altered metabolism, both
      potentially limiting its clinical use. Here, several aspects of the most
      frequently used biomarkers of bone turnover are reviewed, with an emphasis on the
      specific situation represented by CKD. This review is based on the overview
      lecture at the symposium held in Amsterdam, September 23, 2016: "The Bone In
      CKD", organized by the CKD-MBD working group of ERA-EDTA.

PMID- 28502035
TI  - Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and
      Ocular Hypertension: Effectiveness and Treatment Persistence.
AB  - INTRODUCTION: The aim of this study was to investigate the long-term intraocular
      pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin
      analogue, in actual clinical practice and to determine persistency of tafluprost
      as an indicator of its benefit-risk balance. METHODS: This was a large-scale,
      post-marketing, multicenter, non-interventional, open-label, long-term study.
      Patients with glaucoma or ocular hypertension who initiated tafluprost treatment
      were registered and prospectively observed over a 2-year period in the real-world
      setting in Japan. Long-term IOP and safety data were collected. RESULTS: Of the
      4502 patients registered from 553 medical institutions, 4265 patients were
      analyzed. The majority of patients had normal-tension glaucoma (44.4%) and
      primary open-angle glaucoma (37.8%), and patients with ocular hypertension
      constituted 7.0%. Treatment patterns with tafluprost during the study period were
      as follows: naive monotherapy (48.1%), switching monotherapy (18.4%), and
      concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly
      reduced from 18.6 +/- 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2
      year observation period after initiation of tafluprost. Significant IOP-lowering
      effects were shown in various treatment patterns and disease types. Adverse
      reactions were observed in 795 patients (18.64%). Major adverse reactions
      included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid
      hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6%
      and 76.1% of patients were persistent on tafluprost for 1 and 2 years,
      respectively, when discontinuation due to insufficient efficacy or adverse events
      was defined as a treatment failure event. Furthermore, among treatment-naive
      patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0%
      for 1 year and 67.0% for 2 years. CONCLUSION: Tafluprost showed significant long
      term IOP-lowering effects regardless of treatment patterns or diagnosis, with
      minimum safety concerns in the actual clinical practice. The observed treatment
      persistence suggests that tafluprost can be used long term owing to its benefit
      risk profile. FUNDING: Santen Pharmaceutical Co., Ltd., Osaka, Japan.

PMID- 28502034
TI  - Stressful life events during adolescence and risk for externalizing and
      internalizing psychopathology: a meta-analysis.
AB  - The main objective of the present research was to analyze the relations between
      stressful life events and the externalizing and internalizing spectra of
      psychopathology using meta-analytical procedures. After removing the duplicates,
      a total of 373 papers were found in a literature search using several
      bibliographic databases, such as the PsycINFO, Medline, Scopus, and Web of
      Science. Twenty-seven studies were selected for the meta-analytical analysis
      after applying different inclusion and exclusion criteria in different phases.
      The statistical procedure was performed using a random/mixed-effects model based
      on the correlations found in the studies. Significant positive correlations were
      found in cross-sectional and longitudinal studies. A transactional effect was
      then found in the present study. Stressful life events could be a cause, but also
      a consequence, of psychopathological spectra. The level of controllability of the
      life events did not affect the results. Special attention should be given to the
      usage of stressful life events in gene-environment interaction and correlation
      studies, and also for clinical purposes.

PMID- 28502038
TI  - Verbal, Visual, and Intermediary Support for Child Witnesses with Autism During
      Investigative Interviews.
AB  - Three promising investigative interview interventions were assessed in 270
      children (age 6-11 years): 71 with autism spectrum disorder (ASD) and 199 who
      were typically developing (TD). Children received 'Verbal Labels', 'Sketch
      Reinstatement of Context' or 'Registered Intermediary' interviews designed to
      improve interview performance without decreasing accuracy. Children with ASD
      showed no increases in the number of correct details recalled for any of the
      three interview types (compared to a Best-Practice police interview), whereas TD
      children showed significant improvements in the Registered Intermediary and
      Verbal Labels interviews. Findings suggested that children with ASD can perform
      as well as TD children in certain types of investigative interviews, but some
      expected benefits (e.g., of Registered Intermediaries) were not apparent in this
      study.

PMID- 28502036
TI  - Perceptions of Painful Diabetic Peripheral Neuropathy in South-East Asia: Results
      from Patient and Physician Surveys.
AB  - : There are no data on physician-patient communication in painful diabetic
      peripheral neuropathy (pDPN) in the Asia-Pacific region. The objective of this
      study was to examine patient and physician perceptions of pDPN and clinical
      practice behaviors in five countries in South-East Asia. Primary care physicians
      and practitioners, endocrinologists, diabetologists, and patients with pDPN
      completed separate surveys on pDPN diagnosis, impact, management, and physician
      patient interactions in Hong Kong, Malaysia, the Philippines, Taiwan, and
      Thailand. Data were obtained from 100 physicians and 100 patients in each
      country. The majority of physicians (range across countries, 30-85%) were primary
      care physicians and practitioners. Patients were mostly aged 18-55 years and had
      been diagnosed with diabetes for >5 years. Physicians believed pDPN had a greater
      impact on quality of life than did patients (ranges 83-92% and 39-72%,
      respectively), but patients believed pDPN had a greater impact on items such as
      sleep, anxiety, depression, and work than physicians. Physicians considered the
      diagnosis and treatment of pDPN a low priority, which may be reflected in the
      generally low incidence of screening (range 12-65%) and a lack of awareness of
      pDPN. Barriers to treatment included patients' lack of awareness of pDPN. Both
      physicians and patients agreed that pain scales and local language descriptions
      were the most useful tools in helping to describe patients' pain. Most patients
      were monitored upon diagnosis of pDPN (range 55-97%), but patients reported a
      shorter duration of monitoring compared with physicians. Both physicians and
      patients agreed that it was patients who initiated conversations on pDPN.
      Physicians most commonly referred to guidelines from the American Diabetes
      Association or local guidelines for the management of pDPN. This study highlights
      important differences between physician and patient perceptions of pDPN, which
      may impact on its diagnosis and treatment. For a chronic and debilitating
      complication like pDPN, the physician-patient dialogue is central to maximizing
      patient outcomes. Strategies, including education of both groups, need to be
      developed to improve communication. FUNDING: Pfizer.

PMID- 28502039
TI  - Possible involvement of the lipoxygenase and leukotriene signaling pathways in
      cisplatin-mediated renal toxicity.
AB  - PURPOSE: The present study examined the possible involvement of the lipoxygenase
      (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino
      rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after
      one week. Signs of renal dysfunction, including urea and creatinine clearance
      levels and renal histological structure, were investigated. Gene and protein
      expression levels of different LOX pathway enzymes and products, including 5-LOX,
      12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4
      hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl
      (cys) LT receptor types 1 and 2, were also determined in the kidneys using real
      time PCR and western blotting, respectively. The serum and kidney levels of LTB4
      and inflammatory markers were also estimated. RESULTS: CPT renal toxicity was
      established as the creatinine and urea clearance levels were significantly
      reduced, while the serum levels of creatinine and urea were markedly increased.
      We reported a considerable up-regulation in the mRNA and protein expression
      levels of 5-LOX, FLAP, 12-LOX, LTA4 hydrolase, LTC4 synthase, LTB4 receptor, and
      Cys LT receptor types 1 and 2, while 15-LOX expression did not significantly
      change in the CPT group. Additionally, LTB4 and inflammatory indicators in serum
      and renal levels were elevated significantly in the CPT group. Histopathological
      examination clearly showed the nephrotoxic changes in the renal tissues of CPT
      challenged animals. CONCLUSIONS: Our findings suggested, for the first time, the
      participation of LOX enzymes and products in the signaling pathway leading to CPT
      associated nephrotoxicity, which could be the foundation stone for combining LOX
      pathway attenuators with CPT therapy to decrease CPT-associated renal toxicity.

PMID- 28502037
TI  - The Role of the Broader Autism Phenotype and Environmental Stressors in the
      Adjustment of Siblings of Children with Autism Spectrum Disorders in Taiwan and
      the United Kingdom.
AB  - The influence of the broader autism phenotype (BAP) on the adjustment of siblings
      of children with autism has previously been researched mainly in Western
      cultures. The present research evaluated a diathesis-stress model of sibling
      adjustment using a questionnaire study including 80 and 75 mother-typically
      developing sibling dyads in Taiwan and the United Kingdom (UK). UK siblings
      reported elevated adjustment difficulties compared to the Taiwanese sample and to
      normative data. Whilst higher BAP levels were generally associated with greater
      adjustment difficulties, differences were found across cultures and respondents.
      Although significant diathesis-stress interactions were found, these were in the
      opposite direction from those predicted by the model, and differed across
      cultural settings. Implications for culturally-sensitive sibling support are
      considered.

PMID- 28502040
TI  - UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in
      Asians with Lung Cancer: a meta-analysis.
AB  - Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28
      polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians.
      Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower
      frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI
      induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in
      Asians with lung cancer remains controversial. In this meta-analysis, we found a
      higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians
      with lung cancer carrying the UGT1A1*6 polymorphism. However, UGT1A1*28 showed a
      weak correlation with diarrhea, but no significant correlation with neutropenia.
      Neither UGT1A1*6 nor UGT1A1*28 is associated with IRI-based chemotherapy TR.
      These data suggest that the UGT1A1*28 polymorphism may not be a suitable
      biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while
      UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia
      and diarrhea, but not IRI-based chemotherapy TR.

PMID- 28502041
TI  - Glucose Can Epigenetically Alter the Gene Expression of Neurotrophic Factors in
      the Murine Brain Cells.
AB  - Glucose is believed to improve the memory in both human and mice, but the
      detailed insights were mostly elusive. In this study, we focused on two major
      neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast
      growth factor 1 (FGF1), which are believed to be associated with the memory
      enhancement and assessed their expressional regulation among the murine neuronal
      and glial cells. Our findings showed that the glucose administration increased
      phosphorylated Akt, phosphorylated CREB, exon 1- and exon 4-specific BDNF
      transcripts, and FGF1 transcripts that are associated with the epigenetic changes
      expected to open the chromatin and a reduction in histone deacetylase 2 (HDAC2)
      in neurons and astrocytes of the murine hippocampus. The glucose administration
      enhanced the long-term potentiation and the number of dendritic spines in the CA1
      and CA3 subfields of hippocampus. The intrahippocampal injection of short hairpin
      RNA against TrkB canceled the glucose-mediated memory enhancement. Like the
      glucose, we also report that the HDAC inhibitor can enhance the memory through
      the BDNF-TrkB pathway but it targeted different brain cell populations to enhance
      the BDNF and FGF1 transcripts. In addition, the soluble FGF1 treatments
      significantly increased the BDNF expression in astrocytes and neurons, suggesting
      that the glucose-mediated induction of the neurotrophic factors could contribute
      to the memory. Our study provides the valuable insights, explaining the
      distinctive neuronal and glial cell regulation of the neurotrophic factors by
      glucose and HDAC inhibitor, which could likely explain how our brain cells can
      control the release of neurotrophic factors.

PMID- 28502042
TI  - Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the
      Brain.
AB  - Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of
      cytoskeletal remodeling in the brain. Cdk5 is essential for brain development
      during embryogenesis. After birth, it is essential for numerous neuronal
      processes such as learning and memory formation, drug addiction, pain signaling,
      and long-term behavior changes, all of which rely on rapid alterations in the
      cytoskeleton. Cdk5 activity is deregulated in various brain disorders including
      Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and
      ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton,
      loss of synapses, and ultimately neurodegeneration. This review focuses on the
      "good and bad" Cdk5 in the brain and its pleiotropic contribution in regulating
      neuronal actin cytoskeletal remodeling. A vast majority of physiological and
      pathological Cdk5 substrates are associated with the actin cytoskeleton. Thus,
      our special emphasis is on the numerous Cdk5 substrates identified in the past
      two decades such as ephexin1, p27, Mst3, CaMKv, kalirin-7, RasGRF2, Pak1, WAVE1,
      neurabin-1, TrkB, 5-HT6R, talin, drebrin, synapsin I, synapsin III, CRMP1, GKAP,
      SPAR, PSD-95, and LRRK2. These substrates have unraveled the molecular mechanisms
      by which Cdk5 plays divergent roles in regulating neuronal actin cytoskeletal
      dynamics both in healthy and diseased states.

PMID- 28502043
TI  - Different Hippocampus Functional Connectivity Patterns in Healthy Young Adults
      with Mutations of APP/Presenilin-1/2 and APOEepsilon4.
AB  - This study aims to explore the hippocampus-based functional connectivity patterns
      in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE epsilon4
      subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 +/- 2.2
      years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group],
      30 APOE epsilon4 subjects [APOE epsilon4 group], and 30 subjects without the
      above-mentioned genes [control group]) underwent resting-state functional MR
      imaging and neuropsychological assessments. Bilateral hippocampus functional
      connectivity patterns were compared among three groups. The brain regions with
      statistical differences were then extracted, and correlation analyses were
      performed between Z values of the brain regions and neuropsychological results.
      Compared with control group, both APOE epsilon4 group and APP/presenilin-1/2
      group showed increased functional connectivity in medial prefrontal cortex and
      precuneus for the seeds of bilateral hippocampi. The APOE epsilon4 group
      displayed increased functional connectivity from bilateral hippocampi to the left
      middle temporal gyrus compared with the control group. Moreover, compared with
      the APP/presenilin-1/2 group, the APOE epsilon4 group also had markedly increased
      functional connectivity in right hippocampus-left middle temporal gyrus. The Z
      values of right hippocampus-left middle temporal gyrus correlated with various
      neuropsychological results across all the subjects, as well as in APOE epsilon4
      group. Young healthy adults carrying APOE epsilon4 and APP/presenilin-1/2
      displayed different hippocampus functional connectivity patterns, which may
      underlie the discrepant mechanisms of gene-modulated cognitive dysfunction in
      Alzheimer's disease.

PMID- 28502046
TI  - Adapting the Vegetative Vigour Terrestrial Plant Test for assessing ecotoxicity
      of aerosol samples.
AB  - Plants, being recognized to show high sensitivity to air pollution, have been
      long used to assess the ecological effects of airborne contaminants. However,
      many changes in vegetation are now generally attributed to atmospheric deposition
      of aerosol particles; the dose-effect relationships of this process are usually
      poorly known. In contrast to bioindication studies, ecotoxicological tests (or
      bioassays) are controlled and reproducible where ecological responses are
      determined quantitatively. In our study, the No. 227 OECD Guideline for the
      Testing of Chemicals: Terrestrial Plant Test: Vegetative Vigour Test (hereinafter
      referred to as 'Guideline') was adapted and its applicability for assessing the
      ecotoxicity of water-soluble aerosol compounds of aerosol samples was evaluated.
      In the aqueous extract of the sample, concentration of metals, benzenes,
      aliphatic hydrocarbons and PAHs was determined analytically. Cucumis sativus L.
      plants were sprayed with the aqueous extract of urban aerosol samples collected
      in a winter sampling campaign in Budapest. After the termination of the test, on
      day 22, the following endpoints were measured: fresh weight, shoot length and
      visible symptoms. The higher concentrations applied caused leaf necrosis due to
      toxic compounds found in the extract. On the other hand, the extract elucidated
      stimulatory effect at low concentration on both fresh weight and shoot length.
      The test protocol, based on the Guideline, seems sensitive enough to assess the
      phytotoxicity of aqueous extract of aerosol and to establish clear cause-effect
      relationship.

PMID- 28502047
TI  - Evaluation of various solvent systems for lipid extraction from wet microalgal
      biomass and its effects on primary metabolites of lipid-extracted biomass.
AB  - Microalgae have tremendous potential to grow rapidly, synthesize, and accumulate
      lipids, proteins, and carbohydrates. The effects of solvent extraction of lipids
      on other metabolites such as proteins and carbohydrates in lipid-extracted algal
      (LEA) biomass are crucial aspects of algal biorefinery approach. An effective and
      economically feasible algae-based oil industry will depend on the selection of
      suitable solvent/s for lipid extraction, which has minimal effect on metabolites
      in lipid-extracted algae. In current study, six solvent systems were employed to
      extract lipids from dry and wet biomass of Scenedesmus obliquus. To explore the
      biorefinery concept, dichloromethane/methanol (2:1 v/v) was a suitable solvent
      for dry biomass; it gave 18.75% lipids (dry cell weight) in whole algal biomass,
      32.79% proteins, and 24.73% carbohydrates in LEA biomass. In the case of wet
      biomass, in order to exploit all three metabolites, isopropanol/hexane (2:1 v/v)
      is an appropriate solvent system which gave 7.8% lipids (dry cell weight) in
      whole algal biomass, 20.97% proteins, and 22.87% carbohydrates in LEA biomass.
      Graphical abstract: Lipid extraction from wet microalgal biomass and biorefianry
      approach.

PMID- 28502044
TI  - Hippocampal Proteomic Analysis Reveals Distinct Pathway Deregulation Profiles at
      Early and Late Stages in a Rat Model of Alzheimer's-Like Amyloid Pathology.
AB  - The cerebral accumulation and cytotoxicity of amyloid beta (Abeta) is central to
      Alzheimer's pathogenesis. However, little is known about how the amyloid
      pathology affects the global expression of brain proteins at different disease
      stages. In order to identify genotype and time-dependent significant changes in
      protein expression, we employed quantitative proteomics analysis of hippocampal
      tissue from the McGill-R-Thy1-APP rat model of Alzheimer-like amyloid pathology.
      McGill transgenic rats were compared to wild-type rats at early and late
      pathology stages, i.e., when intraneuronal Abeta amyloid burden is conspicuous
      and when extracellular amyloid plaques are abundant with more pronounced
      cognitive deficits. After correction for multiple testing, the expression levels
      of 64 proteins were found to be considerably different in transgenic versus wild
      type rats at the pre-plaque stage (3 months), and 86 proteins in the post-plaque
      group (12 months), with only 9 differentially regulated proteins common to the 2
      time-points. This minimal overlap supports the hypothesis that different
      molecular pathways are affected in the hippocampus at early and late stages of
      the amyloid pathology throughout its continuum. At early stages, disturbances in
      pathways related to cellular responses to stress, protein homeostasis, and
      neuronal structure are predominant, while disturbances in metabolic energy
      generation dominate at later stages. These results shed new light on the
      molecular pathways affected by the early accumulation of Abeta and how the
      evolving amyloid pathology impacts other complex metabolic pathways.

PMID- 28502048
TI  - The effects of cadmium pulse dosing on physiological traits and growth of the
      submerged macrophyte Vallisneria spinulosa and phytoplankton biomass: a mesocosm
      study.
AB  - Pulse inputs of heavy metals are expected to increase with a higher frequency of
      extreme climate events (heavy rain), leading to stronger erosion of contaminated
      and fertilized farmland soils to freshwaters, with potentially adverse effects on
      lake ecosystems. We conducted a 5-month mesocosm study to elucidate the responses
      of the submerged macrophyte Vallisneria spinulosa and phytoplankton to four
      different doses of cadmium (Cd): 0 (control), 0.05, 0.5, and 5 g m-2 (CK, I, II,
      and III, respectively) under mesotrophic conditions. We found that total
      phosphorus concentrations were larger in the three Cd pulse treatments, whereas
      total nitrogen concentrations did not differ among the four treatments. The
      contents of chlorophyll a and soluble sugar in macrophyte leaves decreased in
      III, and total biomass, ramet number, plant height, and total stolon length of
      macrophytes were lower in both II and III. In contrast, abundances of the three
      main phytoplankton taxa-Cyanophyta, Chlorophyta, and Bacillariophyta-did not
      differ among treatments. Total phytoplankton biomass was, however, marginally
      lower in CK than in the Cd treatments. We conclude that exposure to strong Cd
      pulses led to significantly reduced growth of macrophytes, while no obvious
      effect appeared for phytoplankton.

PMID- 28502045
TI  - A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive
      Parkinsonism Revealed Known and Novel Gene Mutations.
AB  - In this study, the role of known Parkinson's disease (PD) genes was examined in
      families with autosomal recessive (AR) parkinsonism to assist with the
      differential diagnosis of PD. Some families without mutations in known genes were
      also subject to whole genome sequencing with the objective to identify novel
      parkinsonism-related genes. Families were selected from 4000 clinical files of
      patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a
      minimum of two affected individuals per family were used as inclusion criteria.
      For disease gene/mutation identification, multiplex ligation-dependent probe
      amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing
      assays were carried out. A total of 116 patients (50 families) were examined.
      Fifty-four patients (46.55%; 22 families) were found to carry pathogenic
      mutations in known genes while a novel gene, not previously associated with
      parkinsonism, was found mutated in a single family (2 patients). Pathogenic
      mutations, including missense, nonsense, frameshift, and exon rearrangements,
      were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion,
      variable phenotypic expressivity was seen across all families.

PMID- 28502049
TI  - Evaluation of carbofuran-mediated toxicity against human lymphocytes and red
      blood cells in simulated wastewater degraded by coagulation-flocculation.
AB  - Coagulation-flocculation in water treatment has been relied upon aluminum (Al)
      and iron (Fe) salts for treatment of contaminants present in source waters
      containing dissolved organic compounds. However, water quality deteriorates day
      by day which makes it urgent to improve the standards of the treatment procedure.
      Coagulation-flocculation-sedimentation performance of ferric chloride and alum
      was comparatively investigated for carbofuran treatment in simulated wastewater.
      Coagulation trails were performed in a jar test at several pH levels and
      coagulant doses to determine reduction efficiencies of carbofuran degradation and
      chemical oxygen demand (COD). Effect of carbofuran on proliferation, viability,
      and direct cytotoxicity was performed using human neuroblastoma cells U-87.
      Direct toxicity of carbofuran on human mononuclear cells and red blood cells
      (RBC) was also analyzed. Carbofuran and its derivatives were found to be
      relatively safe at low concentration (2-5 MUM). However, at slightly higher
      concentration (8 MUM), a moderate loss in viability and proliferative potential
      was observed. Taken together, these results suggest that carbofuran appears to be
      safe at moderate or low concentration with respect to viability of normal human
      lymphocytes and RBC.

PMID- 28502050
TI  - Biogeochemical controls on mercury methylation in the Allequash Creek wetland.
AB  - We measured mercury methylation potentials and a suite of related biogeochemical
      parameters in sediment cores and porewater from two geochemically distinct sites
      in the Allequash Creek wetland, northern Wisconsin, USA. We found a high degree
      of spatial variability in the methylation rate potentials but no significant
      differences between the two sites. We identified the primary geochemical factors
      controlling net methylmercury production at this site to be acid-volatile
      sulfide, dissolved organic carbon, total dissolved iron, and porewater iron(II).
      Season and demethylation rates also appear to regulate net methylmercury
      production. Our equilibrium speciation modeling demonstrated that sulfide likely
      regulated methylation rates by controlling the speciation of inorganic mercury
      and therefore its bioavailability to methylating bacteria. We found that no
      individual geochemical parameter could explain a significant amount of the
      observed variability in mercury methylation rates, but we found significant
      multivariate relationships, supporting the widely held understanding that net
      methylmercury production is balance of several simultaneously occurring
      processes.

PMID- 28502051
TI  - Cadmium impact, accumulation and detection in poplar callus cells.
AB  - Effect of cadmium cations and their interaction with silicon cations was
      determined in poplar calli and expressed as changes in callus growth, cell
      viability and cadmium cation accumulation. Cell viability throughout culture
      versus cadmium cation accumulation in cells is discussed. At the same time, the
      study sought appropriate methods for cadmium cation detection in callus cells and
      also in experiments with low plant material (e.g. protoplasts). Cadmium cations
      were determined by atomic absorption spectroscopy and using fluorescence
      microscopy with a specific cadmium cation fluorescent dye. The detection of
      cadmium cations in callus cells by the latter method appears suitable because the
      callus cells are surrounded by primary cell walls without auto-fluorescence and
      these values fit well with atomic absorption spectroscopy quantification.
      However, the visualisation method has some limits discussed below.

PMID- 28502052
TI  - Variation of microbial communities and functional genes during the biofilm
      formation in raw water distribution systems and associated effects on the
      transformation of nitrogen pollutants.
AB  - This study aimed to investigate the variation of microbial communities and
      functional genes during the biofilm formation in raw water distribution systems
      without prechlorination and associated effects on the transformation of nitrogen
      pollutants by using a designed model pipe system. The results showed the
      transformation of nitrogen pollutants was obvious during the biofilm formation.
      The richness and diversity of the microbial communities changed significantly.
      The higher abundance of Nitrospirae in biofilm samples significantly contributed
      to biological nitrification. In particular, the stable content of Bacteroidetes
      in the biofilm and soluble microbial products released by the biomass might have
      enhanced the increase in dissolved organic nitrogen. In addition, the variation
      tendency of nitrogen functional gene abundances and their strong effects on NH4+
      N, NO2--N, and NO3--N transformation were clearly observed. These findings
      provide new insights into the evolution of microbial communities and functional
      genes during the initial operation period of real-world raw water distribution
      pipes and highlight management and possible safety issues in the subsequent water
      treatment process.

PMID- 28502053
TI  - Synthesis of a ternary Ag/RGO/ZnO nanocomposite via microwave irradiation and its
      application for the degradation of Rhodamine B under visible light.
AB  - Reduced graphene oxide supporting plasmonic photocatalyst (Ag) on ZnO has been
      synthesized via a facile two-step microwave synthesis using RGO/ZnO and AgNO3.
      First step involves fabrication of RGO/ZnO via microwave irradiation. The
      nanocomposites were characterized by X-ray diffraction analysis, transmission
      electron microscopy, Fourier transform infrared spectroscopy, and Raman
      spectroscopy. Ag/RGO/ZnO shows enhanced photoactivity under visible light for the
      degradation of Rhodamine B. Enhanced charge separation and migration have been
      assigned using UV-vis diffuse reflectance spectra, photoluminescence spectra,
      electrochemical impedance spectra, and TCSPC analysis. The improved photoactivity
      of Ag/RGO/ZnO can be ascribed to the prolonged lifetime of photogenerated
      electron-hole pairs and effective interfacial hybridization between RGO and Ag
      with ZnO nanoparticles. Ag nanoparticles can absorb visible light via surface
      plasmon resonance to enhance photocatalytic activity.

PMID- 28502054
TI  - Light absorption of biomass burning and vehicle emission-sourced carbonaceous
      aerosols of the Tibetan Plateau.
AB  - Carbonaceous aerosols over the Tibetan Plateau originate primarily from biomass
      burning and vehicle emissions (BB and VEs, respectively). The light absorption
      characteristics of these carbonaceous aerosols are closely correlated with the
      burning conditions and represent key factors that influence climate forcing. In
      this study, the light absorption characteristics of elemental carbon (EC) and
      water-soluble organic carbon (WSOC) in PM2.5 (fine particulate matter smaller
      than 2.5 MUm) generated from BB and VEs were investigated over the Tibetan
      Plateau (TP). The results showed that the organic carbon (OC)/EC ratios from BB-
      and VE-sourced PM2.5 were 17.62 +/- 10.19 and 1.19 +/- 0.36, respectively. These
      values were higher than the ratios in other regions, which was primarily because
      of the diminished amount of oxygen over the TP. The mass absorption cross section
      of EC (MACEC) at 632 nm for the BB-sourced PM2.5 (6.10 +/- 1.21 m2.g-1) was lower
      than that of the VE-sourced PM2.5 (8.10 +/- 0.98 m2.g-1), indicating that the EC
      content of the BB-sourced PM2.5 was overestimated because of the high OC/EC
      ratio. The respective absorption per mass (alpha/rho) values at 365 nm for the VE
      and BB-sourced PM2.5 were 0.71 +/- 0.17 m2.g-1 and 0.91 +/- 0.18 m2.g-1. The
      alpha/rho value of the VEs was loaded between that of gasoline and diesel
      emissions, indicating that the VE-sourced PM2.5 originated from both types of
      emissions. Because OC and WSOC accounts for most of the carbonaceous aerosols at
      remote area of the TP, the radiative forcing contributed by the WSOC should be
      high, and requires further investigation.

PMID- 28502055
TI  - Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without
      Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity
      Score.
AB  - INTRODUCTION: The estimated cardiovascular risk determined by the different risk
      scores, could be heterogeneous in patients with metabolic syndrome without
      diabetes or vascular disease. This risk stratification could be improved by
      detecting subclinical carotid atheromatosis. AIMS: To estimate the cardiovascular
      risk measured by different scores in patients with metabolic syndrome and analyze
      its association with the presence of carotid plaque. METHODS: Non-diabetic
      patients with metabolic syndrome (Adult Treatment Panel III definition) without
      cardiovascular disease were enrolled. The Framingham score, the Reynolds score,
      the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome
      Severity Calculator were calculated. Prevalence of carotid plaque was determined
      by ultrasound examination. A Receiver Operating Characteristic analysis was
      performed. RESULTS: A total of 238 patients were enrolled. Most patients were
      stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%).
      Using the 2013 ACC/AHA score, 45.3% of the population had a risk >=7.5%. A
      significant correlation was found between classic scores but the agreement
      (concordance) was moderate. The correlation between classical scores and the
      Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of
      carotid plaque was 28.2%. The continuous metabolic syndrome score used in our
      study showed a good predictive power to detect carotid plaque (area under the
      curve 0.752). CONCLUSION: In this population, the calculated cardiovascular risk
      was heterogenic. The prevalence of carotid plaque was high. The Metabolic
      Syndrome Severity Calculator showed a good predictive power to detect carotid
      plaque.

PMID- 28502056
TI  - Overexpression of the nitrate transporter, OsNRT2.3b, improves rice phosphorus
      uptake and translocation.
AB  - KEY MESSAGE: Overexpression of OsNRT2.3b in rice can increase Pi uptake and
      accumulation through advanced root system, enhanced OsPT and OsPHR genes
      expression, and the phloem pH homeostasis. Nitrogen (N) and phosphorus (P) are
      two essential macronutrients for plants. Overexpression of the rice nitrate
      transporter, OsNRT2.3b, can improve rice grain yield and nitrogen use efficiency
      (NUE). Here, OsNRT2.3b overexpression resulted in increased grain yield, straw
      yield, and grain:straw ratio, accompanied by increased P concentrations in the
      leaf blade, leaf sheath, culm, and unfilled rice hulls. Overexpression of
      OsNRT2.3b significantly increased 33Pi uptake compared with WT under 300-MUM Pi
      but not 10-MUM Pi condition in 24 h. Moreover, the OsNRT2.3b-overexpressing rice
      lines showed increased root and shoot biomass, root:shoot ratio, total root
      length root surface area and N, P accumulation under 300- and 10-MUM Pi supply in
      hydroponic solution. The levels of OsPT2, OsPT8, and OsPHR2 expression in roots
      and of OsPT1 and OsPHR2 in shoots were upregulated in OsNRT2.3b-overexpressing
      rice. These results indicated that OsNRT2.3b overexpression can improve rice P
      uptake and accumulation, partially through the advanced root system, enhanced
      gene expression, and the phloem pH regulation function.

PMID- 28502058
TI  - Reversible cerebral vasoconstriction syndrome and antivitamin K anticoagulation:
      challenges of an unusual association.

PMID- 28502057
TI  - MicroRNA-125b in peripheral blood: a potential biomarker for severity and
      prognosis of children with viral encephalitis.
AB  - This study aims to evaluate the effect of peripheral blood miR-125b expression on
      severity and prognosis in children with viral encephalitis (VE). Children with VE
      (severe and mild groups) were grouped into VE group, and 40 healthy children as
      control group. Plasma RNA was extracted, and real-time quantitative PCR was
      conducted to detect miR-125b relative expression. Associations of miR-125b
      expression with clinical characteristics and prognosis of VE children were
      analyzed. Area under ROC curve (AUC) was calculated to evaluate the accuracy of
      the prognostic value of miR-125b. Univariate analysis and logistic regression
      analysis were performed to analyze risk factors of the prognoses of VE children.
      The plasma miR-125b expression was higher in the VE group than in the control
      group and higher in the severe group than the mild group. MiR-125b expression was
      associated with status convulsion, hemiplegia, multiple organ injuries, and
      stress hyperglycemia in VE children. Patients with poor prognosis exhibited
      higher miR-125b expression than those with good prognosis, and the rate of high
      miR-125b expression of the patients with poor prognosis (64.10%, 25/39) was
      higher than that in those with good prognosis (28.92%, 24/83). The AUC of miR
      125b expression to predict prognosis of VE children was 0.833. When the cutoff
      value was 1.715, the diagnostic sensitivity (87.2%), specificity (71.1%), and
      accuracy (76.2%) were the highest. Status convulsion, stress hyperglycemia, and
      miR-125b were considered as risk factors for poor prognosis in VE children.
      Peripheral blood miR-125b expression may be correlated with the severity and
      prognosis of VE in children.

PMID- 28502059
TI  - Dynamics of change in self-reported disability among persons with Parkinson's
      disease after 2 years of follow-up.
AB  - Symptoms of Parkinson's disease (PD) progress over time causing significant
      disability. Yet, change in disability over shorter time periods has not been
      entirely understood. The purpose of this study was to assess the Self-Assessment
      Disability Scale (SADS) in persons with Parkinson's disease (PD) after 2 years of
      follow-up and compare it with the score observed at baseline. Additionally, we
      aimed at evaluating association of motor and non-motor PD features at baseline
      with a higher disability after 2 years of follow-up. A total of 120 consecutive
      persons with PD, who denied falling in the past 6 months, were initially
      recruited. After 2 years of follow-up, 88 (73.3%) persons with PD were evaluated
      for SADS. The total disability (SADS) score did not change after follow-up (p =
      0.529). We observed increase in difficulty at "Getting out of bed" (p = 0.006),
      "Getting up out of armchair" (p = 0.013), "Walking about house/flat" (p = 0.003),
      "Walking outside" (p = 0.010), and "Traveling by public transport" (p = 0.014).
      After adjusting for several potential confounding factors, falls in the past year
      (beta = 8.32, 95% confidence interval (CI) 1.04-15.59) and higher Unified
      Parkinson's Disease Rating Scale part 3 at baseline (beta = 0.26, 95%CI 0.01
      0.51) remained associated with higher PD-related disability. This finding
      suggests that accumulation of overall PD-related disability tends to occur over a
      longer time span. Further studies are needed to gradually assess long-term
      evolution of disability in PD.

PMID- 28502060
TI  - Comparison of Univent tube and EZ blocker in one lung ventilation; airway
      pressures and gas exchange.
AB  - Univent tube (UT) and EZ-blocker were used for one-lung ventilation (OLV). UT is
      a single lumen tube with a small separate lumen containing a bronchial blocker.
      EZ-blocker differs with its unique y-shaped double-cuffed distal end. We aimed to
      compare these two airway devices effects on airway pressures, oxygenation,
      ventilation and haemodynamics during OLV. Patients undergoing elective
      thoracotomy for the first time were included in this prospective randomized
      study. Patients were divided into two groups as UT and EZ. Bronchial blockers
      (BB) placement time was recorded. In lateral decubitus position, airway
      pressures, static compliance, tidal volume (TV), respiratory rate (RR) and
      haemodynamic findings were recorded before inflating the BB cuff (Pre-OLV) and
      during OLV every 15 min. Arterial blood gas (ABG) samples were obtained before
      and during OLV. 70 patients were enrolled in the study. The demographic
      characteristics and data related to anesthesia and surgery were similar in both
      groups. It took longer to place EZ than UT (p = 0.02). Ppeak values were similar
      in both groups. Pplateau was significantly lower at the beginning of OLV (OLV15th
      min) and higher at the end of OLV (pre-DLV) in EZ group compared to UT (p = 0.01,
      p = 0.03). Cstatic were significantly higher at the beginning of OLV (OLV15th
      min) in EZ group compared to UT (p = 0.01). During the following measurements,
      Cstatic values were similar for both groups. Ventilation were achieved with
      similar TV and RR. ABG findings and haemodynamic variables were similar. EZ and
      Univent tube affected the airway pressures, oxygenation, ventilation and
      haemodynamic variables similarly during OLV in patients with normal respiratory
      function. These devices can be alternatives to each other based on clinical
      conditions.

PMID- 28502061
TI  - Validation of administrative case ascertainment algorithms for chronic childhood
      arthritis in Manitoba, Canada.
AB  - We validated case ascertainment algorithms for juvenile idiopathic arthritis
      (JIA) in the provincial health administrative databases of Manitoba, Canada. A
      population-based pediatric rheumatology clinical database from April 1st 1980 to
      March 31st 2012 was used to test case definitions in individuals diagnosed at
      <=15 years of age. The case definitions varied the number of diagnosis codes (1,
      2, or 3), time frame (1, 2 or 3 years), time between diagnoses (ever, >1 day, or
      >=8 weeks), and physician specialty. Positive predictive value (PPV),
      sensitivity, and specificity with 95% confidence intervals (CIs) are reported. A
      case definition of 1 hospitalization or >=2 diagnoses in 2 years by any provider
      >=8 weeks apart using diagnosis codes for rheumatoid arthritis and ankylosing
      spondylitis produced a sensitivity of 89.2% (95% CI 86.8, 91.6), specificity of
      86.3% (95% CI 83.0, 89.6), and PPV of 90.6% (95% CI 88.3, 92.9) when seronegative
      enthesopathy and arthropathy (SEA) was excluded as JIA; and sensitivity of 88.2%
      (95% CI 85.7, 90.7), specificity of 90.4% (95% CI 87.5, 93.3), and PPV of 93.9%
      (95% CI 92.0, 95.8) when SEA was included as JIA. This study validates case
      ascertainment algorithms for JIA in Canadian administrative health data using
      diagnosis codes for both rheumatoid arthritis (RA) and ankylosing spondylitis, to
      better reflect current JIA classification than codes for RA alone. Researchers
      will be able to use these results to define cohorts for population-based studies.

PMID- 28502062
TI  - Significantly lengthened telomere in granulosa cells from women with polycystic
      ovarian syndrome (PCOS).
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among
      women at reproductive age. However, its etiology remains poorly understood.
      Recent studies indicated that telomere length was related to PCOS. However, the
      association between telomere length and PCOS has only been shown in leucocytes
      and remained controversial across different studies. To clarify the association
      between telomere length and PCOS, the current study interrogated telomere length
      not only in leucocytes, but also in follicular granulosa cells, which is
      essential for folliculogenesis and steroidogenesis. METHODS: Seventy-five
      patients with PCOS and 81 controls with mechanical infertility undergoing their
      first in vitro fertilization cycle were enrolled. Their peripheral blood and
      granulosa cells were collected on the oocyte retrieval day. Telomere length of
      both leucocytes in the blood and granulosa cells was assayed by quantitative
      polymerase chain reaction. RESULTS: No significant difference was found in the
      leucocyte telomere length between controls and PCOS patients (0.99 +/- 0.44 vs.
      1.00 +/- 0.38, p = 0.93). Interestingly, when comparing telomere length in
      granulosa cells between controls and PCOS subjects, significantly lengthened
      telomere length was found in PCOS subjects (1.00 +/- 0.37 vs. 1.57+/-0.67, p <
      0.0001). After adjustments for age and body mass index, the p value remained
      significant (p < 0.0001). CONCLUSIONS: This finding reinforced the association
      between telomere abnormalities and PCOS. Given the importance of telomere length
      in cellular proliferation, our findings provided novel insights into the
      pathophysiology of PCOS that abnormalities in telomere length possibly disturb
      folliculogenesis and subsequently result in PCOS.

PMID- 28502064
TI  - Optimization of Water/Oil/Surfactant System for Preparation of Medium-Chain
      Length Poly-3-Hydroxyalkanoates (mcl-PHA)-Incorporated Nanoparticles via
      Nanoemulsion Templating Technique.
AB  - Polymeric nanoparticles gain a widespread interest in food and pharmaceutical
      industries as delivery systems that encapsulate, protect, and release lipophilic
      compounds such as omega-3 fatty acids, fat-soluble vitamins, carotenoids,
      carvedilol, cyclosporine, and ketoprofen. In this study, medium-chain-length poly
      3-hydroxyalkanoate (mcl-PHA)-incorporated nanoparticle was developed via facile
      organic solvent-free nanoemulsion templating technique. The water content
      (W/surfactant-to-oil (S/O)), S/O, and Cremophor EL-to-Span 80 (Cremo/Sp80) ratios
      were first optimized using response surface methodology (RSM) to obtain
      nanoemulsion template prior to incorporation of mcl-PHA. Their effects on
      nanoemulsion formation were investigated. The mcl-PHA-incorporated nanoparticle
      system showed a good preservation capability of beta-carotene and extended
      storage stability.

PMID- 28502063
TI  - Great ape gestures: intentional communication with a rich set of innate signals.
AB  - Great apes give gestures deliberately and voluntarily, in order to influence
      particular target audiences, whose direction of attention they take into account
      when choosing which type of gesture to use. These facts make the study of ape
      gesture directly relevant to understanding the evolutionary precursors of human
      language; here we present an assessment of ape gesture from that perspective,
      focusing on the work of the "St Andrews Group" of researchers. Intended meanings
      of ape gestures are relatively few and simple. As with human words, ape gestures
      often have several distinct meanings, which are effectively disambiguated by
      behavioural context. Compared to the signalling of most other animals, great ape
      gestural repertoires are large. Because of this, and the relatively small number
      of intended meanings they achieve, ape gestures are redundant, with extensive
      overlaps in meaning. The great majority of gestures are innate, in the sense that
      the species' biological inheritance includes the potential to develop each
      gestural form and use it for a specific range of purposes. Moreover, the
      phylogenetic origin of many gestures is relatively old, since gestures are
      extensively shared between different genera in the great ape family. Acquisition
      of an adult repertoire is a process of first exploring the innate species
      potential for many gestures and then gradual restriction to a final (active)
      repertoire that is much smaller. No evidence of syntactic structure has yet been
      detected.

PMID- 28502065
TI  - Polymers for enhanced oil recovery: fundamentals and selection criteria.
AB  - With a rising population, the demand for energy has increased over the years. As
      per the projections, both fossil fuel and renewables will remain as major energy
      source (678 quadrillion BTU) till 2030 with fossil fuel contributing 78% of total
      energy consumption. Hence, attempts are continuously made to make fossil fuel
      production more sustainable and cheaper. From the past 40 years, polymer flooding
      has been carried out in marginal oil fields and have proved to be successful in
      many cases. The common expectation from polymer flooding is to obtain 50%
      ultimate recovery with 15 to 20% incremental recovery over secondary water
      flooding. Both naturally derived polymers like xanthan gum and synthetic polymers
      like partially hydrolyzed polyacrylamide (HPAM) have been used for this purpose.
      Earlier laboratory and field trials revealed that salinity and temperature are
      the major issues with the synthetic polymers that lead to polymer degradation and
      adsorption on the rock surface. Microbial degradation and concentration are major
      issues with naturally derived polymers leading to loss of viscosity and pore
      throat plugging. Earlier studies also revealed that polymer flooding is
      successful in the fields where oil viscosity is quite higher (up to 126 cp) than
      injection water due to improvement in mobility ratio during polymer flooding. The
      largest successful polymer flood was reported in China in 1990 where both
      synthetic and naturally derived polymers were used in nearly 20 projects. The
      implementation of these projects provides valuable suggestions for further
      improving the available processes in future. This paper examines the selection
      criteria of polymer, field characteristics that support polymer floods and
      recommendation to design a large producing polymer flooding.

PMID- 28502067
TI  - Predictive value of salivary microRNA-320a, vascular endothelial growth factor
      receptor 2, CRP and IL-6 in Oral lichen planus progression.
AB  - INTRODUCTION: MicroRNA (miRNA) 320a and vascular endothelial growth factor
      receptor 2 (VEGFR-2) expression as the angiogenic biomarkers might be therapeutic
      targets in Oral lichen planus (OLP). IL-6 and C-reactive protein (CRP) could be
      prognostic in OLP, dysplastic OLP and Oral squamous cell carcinoma (OSCC).
      Therefore, their salivary detections as the noninvasive tools were aimed in this
      study. MATERIALS AND METHODS: Histopathologic examinations were carried out to
      distinguish the patients with dysplastic OLP and OSCC. Salivary microRNA
      expression analysis was performed using RT-qPCR. IL-6 and CRP levels were also
      measured in saliva via ELISA method. VEGFR-2 expression in various sections was
      evaluated using immunohistochemistry. RESULTS: A significant decrease in salivary
      microRNA-320a in dysplastic OLP and OSCC but not in OLP without dysplasia was
      found. VEGFR-2 visualization confirmed the increasing angiogenic process in these
      cases. A significant increase in IL-6 level was detected in cases with OLP,
      dysplastic OLP and OSCC. CRP levels also showed a significant increase in
      dysplastic OLP and OSCC. A positive correlation between IL-6 and CRP levels was
      found. CONCLUSION: Identification of the salivary microRNA-320a and hs-CRP might
      provide a convenient noninvasive predictive tool for dysplastic OLP, whereas IL-6
      could be a diagnostic and therapeutic target in both OLP without dysplasia and
      dysplastic OLP cases.

PMID- 28502068
TI  - Do Not Forget to Look at the Big Toe.

PMID- 28502066
TI  - Ebselen ameliorates beta-amyloid pathology, tau pathology, and cognitive
      impairment in triple-transgenic Alzheimer's disease mice.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease which is
      clinically characterized by memory loss and cognitive decline caused by protein
      misfolding and aggregation. Imbalance between free radicals and the antioxidant
      system is a prominent and early feature in the neuropathology of AD. Selenium
      (Se), a vital trace element with excellent antioxidant potential, is
      preferentially retained in the brain in Se-limited conditions and has been
      reported to provide neuroprotection through resisting oxidative damage. In this
      paper, we studied for the first time the potential of Ebselen, a lipid-soluble
      selenium compound with GPx-like activity, in the treatment of cognitive
      dysfunction and neuropathology of triple-transgenic AD (3 * Tg-AD) mice, AD model
      cell, and primary culture. We demonstrated that Ebselen inhibited oxidative
      stress in both AD model cells and mouse brains with increasing GPx and SOD
      activities and meanwhile reduced p38 mitogen-activated protein kinases
      activities. By decreasing the expression of amyloid precursor protein and beta
      secretase, Ebselen reduced the levels of Abeta in AD neurons and mouse brains,
      especially the most toxic oligomeric form. Besides, mislocation of phosphorylated
      tau in neurons and phosphorylation levels of tau protein at Thr231, Ser396, and
      Ser404 residues were also inhibited by Ebselen, probably by its regulatory roles
      in glycogen synthase kinase 3beta and protein phosphatase 2A activity. In
      addition, Ebselen mitigated the decrease of synaptic proteins including
      synaptophysin and postsynaptic density protein 95 in AD model cells and neurons.
      Consequently, the spatial learning and memory of 3 * Tg-AD mice were
      significantly improved upon Ebselen treatment. This study provides a potential
      novel therapeutic approach for the prevention of AD.

PMID- 28502069
TI  - Topiramate Therapy in Alternating Hemiplegia of Childhood.

PMID- 28502071
TI  - Update from the Abdominal Compartment Society (WSACS) on intra-abdominal
      hypertension and abdominal compartment syndrome: past, present, and future beyond
      Banff 2017.

PMID- 28502072
TI  - The effects of nursing activities on the intra-abdominal pressure of patients at
      risk for intra-abdominal hypertension.
AB  - BACKGROUND: Intra-abdominal hypertension (IAH) occurs frequently in critically
      ill patients, and adds to their morbidity and mortality. There is no published
      evidence on the effects of nursing activities on the intra-abdominal pressure
      (IAP) for patients at risk of IAH. The purpose of this study was to identify the
      effects of hygiene care on the IAP of patients at risk for IAH. METHODS: Hygiene
      care was provided to 34 at-risk patients. IAP was measured prior to initiating
      the hygiene care, immediately after and 10 minutes later. This was a quasi
      experimental, pre-test/ post-test design. RESULTS: The 10 minute post-hygiene
      care measurement of the IAP was significantly lower than the pre or immediate
      post-measurement of the IAP. There were no significant changes in the mean
      arterial pressure (MAP) or the abdominal perfusion pressure (APP). CONCLUSIONS:
      It is safe and possibly therapeutic to provide hygiene care to patients at risk
      for IAH.

PMID- 28502073
TI  - Early impact of abdominal compartment syndrome on liver, kidney and lung damage
      in a rodent model.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) sometimes occurs in critically
      ill patients following damage control surgery. The purpose of the present study
      was to develop a model of ACS and to evaluate its pathologic impact on liver,
      kidney, and lung morphology. METHODS: Twenty Wistar rats (mass 300-350 g) were
      randomly divided into four groups: 1) intra-abdominal hypertension (IAH): a
      laparotomy was performed and the abdomen packed with cotton until an intra
      abdominal pressure (IAP) of 15 mm Hg was reached; 2) hypovolemia (HYPO): blood
      was withdrawn until a mean arterial pressure ~60 mm Hg was reached; 3) IAH + HYPO
      (to resemble clinical ACS); and 4) sham surgery. After 3 hours of protective
      mechanical ventilation, the animals were euthanized and the liver, kidney and
      lungs removed to examine the degree of tissue damage. RESULTS: IAH resulted in
      the following: oedema and neutrophil infiltration in the kidney; necrosis,
      congestion, and microsteatosis in the liver; and alveolar collapse, haemorrhage,
      interstitial oedema, and neutrophil infiltration in the lungs. Furthermore, IAH
      was associated with greater cell apoptosis in the kidney, liver and lungs
      compared to sham surgery. HYPO led to oedema and neutrophil infiltration in the
      kidney. The combination of IAH and HYPO resulted in all the aforementioned
      changes in lung, kidney and liver tissue, as well as exacerbation of the
      inflammatory process in the kidney and liver and kidney cell necrosis and
      apoptosis. CONCLUSIONS: Intra-abdominal hypertension by itself is associated with
      kidney, liver and lung damage; when combined with hypovolemia, it leads to
      further impairment and organ damage.

PMID- 28502074
TI  - Causes and consequences of mesenteric embolization after endovascular aorto-iliac
      intervention - a nested case control study.
AB  - BACKGROUND: Causes and consequences of mesenteric embolization after endovascular
      aorto-iliac procedures have not been studied adequately. METHODS: Consecutive
      patients with mesenteric embolization after endovascular aorto-iliac intervention
      between 2011 and 2015 (case-group, n = 9) were investigated and compared with
      age, gender and procedure-matched random controls (n = 36). RESULTS: Compared to
      the control group, a higher proportion of patients with mesenteric embolization
      were current smokers (89% vs. 53%; P = 0.048) and had renal insufficiency at
      admission (44% vs. 11%; P = 0.019). In patients treated for aorto-iliac occlusive
      disease, aortic irregularity (shagginess) was more severe (P = 0.015), visceral
      thrombus volume was larger (P = 0.004) and operation-time was longer (P = 0.009)
      among the case-group. However, no differences were found between cases with
      mesenteric embolization caused by endovascular aortic aneurysm repair versus
      controls. Myoglobin, arterial blood lactate, aspartate aminotransferase, alanine
      aminotransferase and pancreatic amylase levels were elevated in 100%, 67%, 89%,
      89%, 89% and 56% of patients with mesenteric embolization, respectively. Overall
      in-hospital mortality among cases was 33% (3/9). The in-hospital mortality was
      17% (1/6) in patients treated with open abdomen therapy, of whom five were
      managed with stomas. CONCLUSION: Smoking cessation, careful patient selection and
      procedure planning with identification of severe shaggy aortas might prevent
      mesenteric embolization during aorto-iliac procedures. In suspected cases of
      mesenteric embolization, elevated myoglobin and arterial blood lactate may be
      indicative of this complication. Aspartate and alanine aminotranferases, as well
      as pancreatic amylase, are also relevant tests to assess the extent of organ
      ischaemia. Damage control with open abdomen therapy and the creation of stomas
      seem justifiable in order to improve survival in this complex situation.

PMID- 28502070
TI  - Sleep in Children with Autism Spectrum Disorder.
AB  - The purposes of this paper are to provide an overview of the state of the science
      of sleep in children with autism spectrum disorder (ASD), present hypotheses for
      the high prevalence of insomnia in children with ASD, and present a practice
      pathway for promoting optimal sleep. Approximately two thirds of children with
      ASD have chronic insomnia, and to date, the strongest evidence on promoting sleep
      is for sleep education, environmental changes, behavioral interventions, and
      exogenous melatonin. The Sleep Committee of the Autism Treatment Network (ATN)
      developed a practice pathway, based on expert consensus, to capture best
      practices for screening, identification, and treatment for sleep problems in ASD
      in 2012. An exemplar case is presented to integrate key constructs of the
      practice pathway and address arousal and sensory dysregulation in a child with
      ASD and anxiety disorder. This paper concludes with next steps for dissemination
      of the practice pathway and future directions for research of sleep problems in
      ASD.

PMID- 28502076
TI  - Scalp threading with polydioxanone monofilament threads: a novel, effective and
      safe modality for hair restoration.

PMID- 28502075
TI  - Vacuum-assisted wound closure and mesh-mediated fascial traction for open abdomen
      therapy - a systematic review.
AB  - BACKGROUND: The aim of this paper was to review the literature on vacuum-assisted
      wound closure and mesh-mediated fascial traction (VAWCM) in open abdomen therapy.
      It was designed as systematic review of observational studies. METHODS: A Pub
      Med, EMBASE and Cochrane search from 2007/01-2016/07 was performed combining the
      Medical Subject Headings "vacuum", "mesh-mediated fascial traction", "temporary
      abdominal closure", "delayed abdominal closure", "open abdomen", "abdominal
      compartment syndrome", "negative pressure wound therapy" or "vacuum assisted
      wound closure". RESULTS: Eleven original studies were found including patients
      numbering from 7 to 111. Six studies were prospective and five were
      retrospective. Nine studies were on mixed surgical (n = 9), vascular (n = 6) and
      trauma (n = 6) patients, while two were exclusively on vascular patients. The
      primary fascial closure rate per protocol varied from 80-100%. The time to
      closure of the open abdomen varied between 9-32 days. The entero-atmospheric
      fistula rate varied from 0-10.0%. The in-hospital survival rate varied from 57
      100%. In the largest prospective study, the incisional hernia rate among
      survivors at 63 months of median follow-up was 54% (27/50), and 16 (33%) repairs
      out of 48 incisional hernias were performed throughout the study period. The
      study patients reported lower short form health survey (SF-36) scores than the
      mean reference population, mainly dependent on the prevalence of major co
      morbidities. There was no difference in SF-36 scores or a modified ventral hernia
      pain questionnaire (VHPQ) at 5 years of follow up between those with versus those
      without incisional hernias. CONCLUSIONS: A high primary fascial closure rate can
      be achieved with the vacuum-assisted wound closure and meshmediated fascial
      traction technique in elderly, mainly non-trauma patients, in need of prolonged
      open abdomen therapy.

PMID- 28502077
TI  - Life [ageing] is like riding a bicycle. To keep your [coronary and heart] balance
      you must keep moving.

PMID- 28502079
TI  - Microstructure alterations in the hypothalamus in cranially radiated childhood
      leukaemia survivors but not in craniopharyngioma patients unaffected by
      hypothalamic damage.
AB  - OBJECTIVE: Metabolic complications are frequent in childhood leukaemia (ALL)
      survivors treated with cranial radiotherapy (CRT). These complications are
      potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO)
      craniopharyngioma (CP) survivors without HT involvement are spared overt obesity.
      Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by
      fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and
      radial diffusivity (RD). We used DTI to determine the integrity of the
      microstructure of the HT in ALL survivors. DESIGN: Case-control study. PATIENTS:
      Three groups were included: (i) 27 CRT treated ALL survivors on hormone
      supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without
      HT involvement and (iii) 27 matched controls. MEASUREMENTS: DTI parameters of the
      HT were measured and body composition. RESULTS: Microstructural alterations in
      the HT were more severe in ALL survivors with a BMI >=25 than with BMI <25.
      Compared to controls, ALL survivors had reduced FA (P=.04), increased MD
      (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT,
      ALL survivors with a BMI >=25 showed elevated MD (P=.03) and AD (P=.02) compared
      to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between
      CP survivors and controls. CONCLUSIONS: Long-term follow-up after CRT for ALL DTI
      measures were affected in the HT despite complete hormone replacement. The
      present data suggest that ALL survivors have demyelination and axonal loss in the
      HT.

PMID- 28502078
TI  - Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential
      prognostic marker for liver metastasis of colorectal cancer.
AB  - Colorectal cancer is a common cancer and a leading cause of cancer-related death
      worldwide. The liver is a dominant metastatic site for patients with colorectal
      cancer. Molecular mechanisms that allow colorectal cancer cells to form liver
      metastases are largely unknown. Activation of epithelial-mesenchymal transition
      is the key step for metastasis of cancer cells. We recently reported that dual
      specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal
      transition in breast cancer and ovarian serous adenocarcinoma. The aim of this
      study is to clarify whether DYRK2 regulates liver metastases of colorectal
      cancer. We show that the ability of cell invasion and migration was abrogated in
      DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic
      lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we
      found that patients whose liver metastases expressed low DYRK2 levels had
      significantly worse overall and disease-free survival. Given the findings that
      DYRK2 regulates cancer cell metastasis, we concluded that the expression status
      of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.

PMID- 28502080
TI  - Contemporary role of ureterolysis in retroperitoneal fibrosis: treatment of last
      resort or first intent? An analysis of 50 cases.
AB  - OBJECTIVE: To determine the outcomes of open ureterolysis in a contemporary
      cohort of patients presenting with ureteric obstruction secondary to
      retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: We conducted a prospective
      analysis of 50 patients undergoing open ureterolysis and omental wrap between
      January 2012 and January 2016 in a single centre, managed by a multi-disciplinary
      RPF team. Patients had a minimum follow-up of 1 year. Indications were:
      nephrostomy-dependent drainage (n = 5); stent failure as evidenced by persistent
      hydronephrosis (n = 20); severe stent symptoms (n = 22); and patient choice/pre
      emptive (n = 3). Outcome measures were stent-free rate; change in renal function
      post-ureterolysis; operating variables (operating time, blood loss,
      complications, length of hospital stay); and need for further intervention.
      RESULTS: Of the 50 patients, 48 (96%) were stent-free at 3 months and 47/50 (94%)
      were stent-free at 12 months. The median (interquartile range [IQR]) changes in
      glomerular filtration rate, according to these indication groups, at 1 year were:
      overall +6 (-4 to +22)% (P < 0.05); stent failure +25 (+5 to +27)% (P < 0.001);
      stent symptoms +0 (-17 to +6)% (P = 0.834); nephrostomy-dependent drainage -10 (
      19 to -2)% (P = 0.731); and pre-emptive 0 (0 to +8)% (P = 0.5). A total of 11/50
      patients (22%) underwent additional procedures: nephrectomy, n = 7; uretero
      ureterostomy, n = 1; aneurysm repair, n = 1; 1 Boari flap, n = 1; and ureteric re
      implant, n = 1. Serious complications (Clavien III or IV) occurred in 12% of
      patients. The median (IQR) blood loss was 390 (20-1,200) mL and the median (IQR)
      length of hospital stay was 8 (3-21) days. CONCLUSIONS: This study suggests that
      for patients with ureteric obstruction caused by RPF, contemporary ureterolysis
      performed by a high-volume specialist team can successfully render patients stent
      or nephrostomy-free without compromising renal function. The results suggest
      that ureterolysis should be considered in all patients who present with ureteric
      obstruction caused by RPF that does not respond quickly to standard treatment.

PMID- 28502081
TI  - Simultaneous modification of three homoeologs of TaEDR1 by genome editing
      enhances powdery mildew resistance in wheat.
AB  - Wheat (Triticum aestivum L.) incurs significant yield losses from powdery mildew,
      a major fungal disease caused by Blumeria graminis f. sp. tritici (Bgt). enhanced
      disease resistance1 (EDR1) plays a negative role in the defense response against
      powdery mildew in Arabidopsis thaliana; however, the edr1 mutant does not show
      constitutively activated defense responses. This makes EDR1 an ideal target for
      approaches using new genome-editing tools to improve resistance to powdery
      mildew. We cloned TaEDR1 from hexaploid wheat and found high similarity among the
      three homoeologs of EDR1. Knock-down of TaEDR1 by virus-induced gene silencing or
      RNA interference enhanced resistance to powdery mildew, indicating that TaEDR1
      negatively regulates powdery mildew resistance in wheat. We used CRISPR/Cas9
      technology to generate Taedr1 wheat plants by simultaneous modification of the
      three homoeologs of wheat EDR1. No off-target mutations were detected in the
      Taedr1 mutant plants. The Taedr1 plants were resistant to powdery mildew and did
      not show mildew-induced cell death. Our study represents the successful
      generation of a potentially valuable trait using genome-editing technology in
      wheat and provides germplasm for disease resistance breeding.

PMID- 28502082
TI  - Desynchronizations in bee-plant interactions cause severe fitness losses in
      solitary bees.
AB  - Global warming can disrupt mutualistic interactions between solitary bees and
      plants when increasing temperature differentially changes the timing of
      interacting partners. One possible scenario is for insect phenology to advance
      more rapidly than plant phenology. However, empirical evidence for fitness
      consequences due to temporal mismatches is lacking for pollinators and it remains
      unknown if bees have developed strategies to mitigate fitness losses following
      temporal mismatches. We tested the effect of temporal mismatches on the fitness
      of three spring-emerging solitary bee species, including one pollen specialist.
      Using flight cages, we simulated (i) a perfect synchronization (from a bee
      perspective): bees and flowers occur simultaneously, (ii) a mismatch of 3 days
      and (iii) a mismatch of 6 days, with bees occurring earlier than flowers in the
      latter two cases. A mismatch of 6 days caused severe fitness losses in all three
      bee species, as few bees survived without flowers. Females showed strongly
      reduced activity and reproductive output compared to synchronized bees. Fitness
      consequences of a 3-day mismatch were species-specific. Both the early-spring
      species Osmia cornuta and the mid-spring species Osmia bicornis produced the same
      number of brood cells after a mismatch of 3 days as under perfect
      synchronization. However, O. cornuta decreased the number of female offspring,
      whereas O. bicornis spread the brood cells over fewer nests, which may increase
      offspring mortality, e.g. due to parasitoids. The late-spring specialist Osmia
      brevicornis produced fewer brood cells even after a mismatch of 3 days.
      Additionally, our results suggest that fitness losses after temporal mismatches
      are higher during warm than cold springs, as the naturally occurring temperature
      variability revealed that warm temperatures during starvation decreased the
      survival rate of O. bicornis. We conclude that short temporal mismatches can
      cause clear fitness losses in solitary bees. Although our results suggest that
      bees have evolved species-specific strategies to mitigate fitness losses after
      temporal mismatches, the bees were not able to completely compensate for impacts
      on their fitness after temporal mismatches with their food resources.

PMID- 28502084
TI  - Conspecific and not performance-based attraction on immigrants drives colony
      growth in a waterbird.
AB  - Local recruitment and immigration play an important part in the dynamics and
      growth of animal populations. However, their estimation and incorporation into
      open population models is, in most cases, problematic. We studied factors
      affecting the growth of a recently established colony of Eurasian spoonbill
      (Platalea leucorodia) and assessed the contribution of local recruits, i.e. birds
      born in the colony, and immigrants, i.e. birds of unknown origin, to colony
      growth. We applied an integrated population model that accounts for uncertainty
      in breeding state assignment and merges population surveys, local fecundity and
      individual longitudinal data of breeding and non-breeding birds, to estimate
      demographic rates and the relative role of recruitment and immigration in driving
      the local dynamics. We also used this analytical framework to assess the degree
      of support for the 'performance-based' and 'conspecific attraction' hypotheses as
      possible mechanisms of colony growth. Among the demographic rates, only
      immigration was positively and significantly correlated with population growth
      rate. In addition, the number of immigrants settling in the colony was positively
      correlated with colony size in the previous and current year, but was not
      correlated with fecundity of the previous year. Our results suggest that the
      variation in immigration affected colony dynamics and that conspecific attraction
      likely triggered the relevant role of immigration in the growth of a recently
      formed waterbird colony, supporting the need of including immigration in
      population analysis.

PMID- 28502083
TI  - In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and
      squamous cell carcinoma using dynamic optical coherence tomography.
AB  - BACKGROUND: A clear distinction between actinic keratosis (AK), Bowen's disease
      (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and
      dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a
      novel angiographic variant of OCT that allows for non-invasive, in vivo
      evaluation of the cutaneous microvascular morphology. OBJECTIVE: To investigate
      the microvascular structures of AK, BD and invasive SCC using D-OCT in order to
      gain insights into the microvascular morphology of lesions in the spectrum of
      keratinocyte skin cancers. METHODS: Forty-seven patients with a total of 54
      lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still images
      of AK, BD and SCC at three predefined skin depths were prepared and randomized,
      creating a study set of 162 D-OCT images. Three observers performed blinded
      evaluations of the randomized study set assessing multiple parameters including
      the different types of vascular morphology. Non-blinded quantitative measurements
      of vascular diameter were also performed. RESULTS: The blinded observer analysis
      suggests that D-OCT evaluation of the vascular morphology may aid in
      distinguishing AK, BD and SCC lesions. We identified two vascular shapes that
      presented significantly differently across the lesion types, namely 'blobs' and
      'curves'. A strong presence of blobs at 300 MUm skin depth was characteristically
      seen in a third of BD cases, while not or only slightly present in AK and SCC
      lesions. Vascular curves were predominantly present in AK lesions. CONCLUSION: We
      identified various vascular D-OCT features that may aid in non-invasively
      differentiating subtypes within the keratinocyte skin cancer spectrum.

PMID- 28502085
TI  - Pathogenicity of ADAR1 mutation in a Chinese family with dyschromatosis
      symmetrica hereditaria.

PMID- 28502087
TI  - Palmar melanoma: a tertiary centre experience.

PMID- 28502086
TI  - Does influenza pandemic preparedness and mitigation require gain-of-function
      research?
AB  - The risk and benefits of gain-of-function studies on influenza A have been widely
      debated since 2012 when the methods to create two respiratory transmissible H5N1
      mutant isolates were published. Opponents of gain-of-function studies argue the
      biosecurity risk is unacceptable, while proponents cite potential uses for
      pandemic surveillance, preparedness and mitigation. In this commentary, we
      provide an overview of the background and applications of gain-of-function
      research and argue that the anticipated benefits have yet to materialize while
      the significant risks remain.

PMID- 28502088
TI  - Limited impact of awareness-raising campaigns on hepatitis C testing practices
      among general practitioners.
AB  - The global hepatitis strategy calls for increased effort to diagnose those
      infected, with a target of 90% diagnosed by 2030. Scotland's Action Plan on
      Hepatitis C included awareness-raising campaigns, undertaken during 2008-2011, to
      promote testing by general practitioners. We examined hepatitis C virus (HCV)
      testing practice among general practitioners before and following these
      campaigns. Scottish general practitioners were surveyed, using Dillman's method,
      in 2007 and 2013; response rates were 69% and 60%, respectively. Most respondents
      offer testing when presented with a risk history (86% in 2007, 88% in 2013) but
      only one-fifth actively sought out risk factors (19% in 2007, 21% in 2013).
      Testing was reportedly always/almost always/usually offered to people who inject
      drugs (84% in 2007, 87% in 2013). Significant improvements in the offer of
      testing were reported in patients with abnormal LFTs (41% in 2007, 65% in 2013,
      P<.001) and who had received medical/dental treatment in high prevalence
      countries (14% in 2007, 24% in 2013, P=.001). In 2013, 25% of respondents had
      undertaken HCV-related continued professional development. This group was
      significantly more likely to actively seek out risk factors (P=.009) but only
      significantly more likely to offer a test to patients who had received
      medical/dental treatment in high prevalence countries (P=.001). Our findings
      suggest that government-led awareness raising campaigns have limited impact on
      general practitioners' testing practices. If the majority of the HCV-infected
      population are to be diagnosed, practitioner-based or physician-centred
      interventions should be considered alongside educational initiatives targeted at
      professionals.

PMID- 28502090
TI  - Successful use of lipid emulsion to resuscitate a foal after intravenous
      lidocaine induced cardiovascular collapse.
AB  - BACKGROUND: Lipid emulsion has been reported to be effective for the treatment of
      local anaesthetic overdoses in rats, dogs and man. OBJECTIVES: To describe the
      successful treatment of cardiovascular lidocaine toxicity in a foal with
      intravenous lipid administration. STUDY DESIGN: Observational study: case report.
      METHODS: An 8-month-old Arabian cross foal was anaesthetised for removal of the
      right alar fold and nasal plate. Anaesthesia was maintained with isoflurane in
      oxygen and lidocaine administered with a loading dose followed by a continuous
      rate infusion (CRI). The anaesthetic period was uneventful and 30 min before
      expected termination of the procedure lidocaine infusion was stopped. A sudden
      drop in mean arterial blood pressure was then observed. The ECG signal was lost,
      the end tidal CO2 tension dropped from 40 to 10 mmHg, corneal reflex was absent
      and asystole diagnosed. Cardiopulmonary resuscitation manoeuvres were immediately
      initiated, but epinephrine and atropine were unsuccessfully administered. Lipid
      emulsion was administered and the heart rate and arterial blood pressure
      gradually returned to normal. RESULTS: The foal recovered consciousness 3 h
      later, regained its sternal position, was responsive and 20 h later was able to
      stand up alone. MAIN LIMITATIONS: It will be necessary to evaluate a greater
      number of cases to determine the effectiveness of lipids in foals intoxicated
      with lidocaine. CONCLUSION: Intravenous lipid emulsion may be helpful in the
      treatment of potentially lethal cardiotoxicity attributable to lidocaine overdose
      in the foal.

PMID- 28502089
TI  - Association between cytokine profile and transcription factors produced by T-cell
      subsets in early- and late-onset pre-eclampsia.
AB  - Pre-eclampsia (PE) is an obstetric pathology characterized by abnormal activation
      of the innate and adaptive immune systems dependent on the imbalance of T helper
      subsets. The present study aimed to evaluate the gene and protein expression of T
      helper type 1 (Th1)/Th2/Th17/regulatory T (Treg) cell transcription factors in
      peripheral blood lymphocytes from pregnant women with PE employing quantitative
      RT-PCR and flow cytometry techniques, as well as the cytokine profile produced by
      these CD4+ T-cell subsets in the plasma of pregnant women with PE, classified as
      early-onset PE (n = 20), late-onset PE (n = 20) and normotensive pregnant women
      (n = 20). Results showed a higher percentage of CD4+ T cells expressing the RORc
      transcription factor (Th17) and a lower percentage of cells expressing FoxP3
      (Treg) in women with early-onset PE compared with late-onset PE and normotensive
      groups. A lower gene expression of GATA-3 transcription factor was detected in
      cells of women with early-onset PE compared with the late-onset PE group.
      Endogenous plasma levels of interleukin-6 (IL-6), IL-17 and tumour necrosis
      factor-alpha were significantly higher in the early-onset PE group than in the
      late-onset PE and normotensive groups, whereas IL-4 (Th2 profile) and IL-22 (Th17
      profile), were not significantly different between the studied groups. The
      endogenous levels of transforming growth factor-beta and IL-10 were significantly
      lower in the pre-eclamptic than in the normotensive groups of the same
      gestational age, with a significant difference between early- and late-onset PE.
      The results show that in women with PE there is an imbalance between inflammatory
      and anti-inflammatory profiles in CD4+ T-cell subsets, with polarization to Th17
      profiles in the early-onset PE, considered as the severe form of PE.

PMID- 28502092
TI  - HIV/HCV coinfection and the risk of cardiovascular disease: A meta-analysis.
AB  - The emergence of improved antiretroviral therapy has increased the life
      expectancy of human immunodeficiency virus (HIV)-infected individuals, although
      there is an increased susceptibility to developing cardiovascular diseases (CVD).
      The risk for CVD is purported to be even higher among people with HIV and
      hepatitis C virus (HCV) coinfection because of the increased inflammatory
      response, which may synergistically impact CVD risk. However, studies comparing
      CVD outcomes between HIV alone and HIV/HCV individuals have been discordant.
      Accordingly, we conducted a meta-analysis to clarify and quantify the association
      between HIV/HCV coinfection and the risk for CVD. We searched EMBASE, CINAHL,
      Google Scholar, PubMed, and Web of Science from inception to December 2016 to
      identify studies that provided information on HIV/HCV coinfection and CVD,
      defined as coronary artery disease, congestive heart failure and stroke. We used
      a random-effects model to abstract and pool data on the hazard ratios (HRs) for
      CVD. HRs were adjusted for traditional CVD risk factors including age, sex,
      smoking, hypertension, diabetes and LDL cholesterol. Among the 283 articles
      reviewed, four cohort studies met inclusion criteria with a total of 33 723
      participants. The pooled adjusted HRs for the association between HIV/HCV
      coinfection and CVD were 1.24 (95% CI: 1.07-1.40) compared to HIV monoinfection.
      The test for heterogeneity was not statistically significant (I2 =0.0%, P=.397).
      In conclusion, individuals with HIV/HCV coinfection had an increased CVD risk
      compared to those with HIV monoinfection. More research is needed to further
      examine the nature of this association, and response to traditional risk
      reduction therapies.

PMID- 28502091
TI  - Increased Pretransplant Frequency of CD28+ CD4+ TEM Predicts Belatacept-Resistant
      Rejection in Human Renal Transplant Recipients.
AB  - While most human T cells express the CD28 costimulatory molecule constitutively,
      it is well known that age, inflammation, and viral infection can drive the
      generation of CD28null T cells. In vitro studies have demonstrated that CD28null
      cell effector function is not impacted by the presence of the CD28 costimulation
      blocker belatacept. As such, a prevailing hypothesis suggests that CD28null cells
      may precipitate costimulation blockade-resistant rejection. However, CD28+ cells
      possess more proliferative and multifunctional capacity, factors that may
      increase their ability to successfully mediate rejection. Here, we performed a
      retrospective immunophenotypic analysis of adult renal transplant recipients who
      experienced acute rejection on belatacept treatment as compared to those who did
      not. Intriguingly, our findings suggest that patients possessing higher frequency
      of CD28+ CD4+ TEM prior to transplant were more likely to experience acute
      rejection following treatment with a belatacept-based immunosuppressive regimen.
      Mechanistically, CD28+ CD4+ TEM contained significantly more IL-2 producers. In
      contrast, CD28null CD4+ TEM isolated from stable belatacept-treated patients
      exhibited higher expression of the 2B4 coinhibitory molecule as compared to those
      isolated from patients who rejected. These data raise the possibility that
      pretransplant frequencies of CD28+ CD4+ TEM could be used as a biomarker to
      predict risk of rejection following treatment with belatacept.

PMID- 28502094
TI  - PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions.
AB  - AIMS: PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a
      promising treatment in relapsed/refractory disease, used eventually in
      combination with traditional chemotherapy in different cancer settings. To date,
      no data are available concerning PD-L1 expression in ampulla of Vater carcinoma
      and its pre-invasive lesions. METHODS AND RESULTS: We assessed the
      immunohistochemical expression of PD-L1 in a series of 26 ampullary
      adenocarcinomas, 50 ampullary dysplastic lesions and 10 normal duodenal mucosa
      samples. Moreover, in all cases DNA mismatch repair proteins status was
      investigated. PD-L1 was expressed in seven of 26 (26.9%) invasive carcinomas and
      three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven
      of 10) were intestinal-type and poorly differentiated (G3). The number of PD-L1
      positive stromal lymphoid cells was significantly higher in dysplastic and
      invasive lesions than in the normal samples (P = 0.011). Nineteen dysplastic
      lesions and eight invasive carcinomas did not show any evident epithelial or
      stromal PD-L1 expression. Four of the carcinomas were mismatch repair-deficient
      and two of these were PD-L1-positive. Furthermore, mismatch repair-deficient
      lesions showed a significantly higher average of PD-L1-positive stromal lymphoid
      cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; P <
      0.001). CONCLUSIONS: The present results suggest a role of the PD-1/PD-L1 axis in
      ampullary adenocarcinomas, and therefore this may also prompt consideration of
      checkpoint immunotherapy as a novel promising treatment for these tumours.

PMID- 28502096
TI  - Circumscribed palmoplantar hypokeratosis: successful treatment with the 10 600-nm
      carbon dioxide fractional laser.

PMID- 28502093
TI  - The TLR4-TRIF pathway can protect against the development of experimental
      allergic asthma.
AB  - The Toll-like receptor (TLR) adaptor proteins myeloid differentiating factor 88
      (MyD88) and Toll, interleukin-1 receptor and resistance protein (TIR) domain
      containing adaptor inducing interferon-beta (TRIF) comprise the two principal
      limbs of the TLR signalling network. We studied the role of these adaptors in the
      TLR4-dependent inhibition of allergic airway disease and induction of CD4+ ICOS+
      T cells by nasal application of ProtollinTM, a mucosal adjuvant composed of TLR2
      and TLR4 agonists. Wild-type (WT), Trif-/- or Myd88-/- mice were sensitized to
      birch pollen extract (BPEx), then received intranasal Protollin followed by
      consecutive BPEx challenges. Protollin's protection against allergic airway
      disease was TRIF-dependent and MyD88-independent. TRIF deficiency diminished the
      CD4+ ICOS+ T-cell subsets in the lymph nodes draining the nasal mucosa, as well
      as their recruitment to the lungs. Overall, TRIF deficiency reduced the
      proportion of cervical lymph node and lung CD4+ ICOS+ Foxp3- cells, in
      particular. Adoptive transfer of cervical lymph node cells supported a role for
      Protollin-induced CD4+ ICOS+ cells in the TRIF-dependent inhibition of airway
      hyper-responsiveness. Hence, our data demonstrate that stimulation of the TLR4
      TRIF pathway can protect against the development of allergic airway disease and
      that a TRIF-dependent adjuvant effect on CD4+ ICOS+ T-cell responses may be a
      contributing mechanism.

PMID- 28502095
TI  - The impact of age and frailty on ventricular structure and function in C57BL/6J
      mice.
AB  - KEY POINTS: Heart size increases with age (called hypertrophy), and its ability
      to contract declines. However, these reflect average changes that may not be
      present, or present to the same extent, in all older individuals. That aging
      happens at different rates is well accepted clinically. People who are aging
      rapidly are frail and frailty is measured with a 'frailty index'. We quantified
      frailty with a validated mouse frailty index tool and evaluated the impacts of
      age and frailty on cardiac hypertrophy and contractile dysfunction. Hypertrophy
      increased with age, while contractions, calcium currents and calcium transients
      declined; these changes were graded by frailty scores. Overall health status,
      quantified as frailty, may promote maladaptive changes associated with cardiac
      aging and facilitate the development of diseases such as heart failure. To
      understand age-related changes in heart structure and function, it is essential
      to know both chronological age and the health status of the animal. ABSTRACT: On
      average, cardiac hypertrophy and contractile dysfunction increase with age.
      Still, individuals age at different rates and their health status varies from fit
      to frail. We investigated the influence of frailty on age-dependent ventricular
      remodelling. Frailty was quantified as deficit accumulation in adult (~7 months)
      and aged (~27 months) C57BL/6J mice by adapting a validated frailty index (FI)
      tool. Hypertrophy and contractile function were evaluated in Langendorff-perfused
      hearts; cellular correlates/mechanisms were investigated in ventricular myocytes.
      FI scores increased with age. Mean cardiac hypertrophy increased with age, but
      values in the adult and aged groups overlapped. When plotted as a function of
      frailty, hypertrophy was graded by FI score (r = 0.67-0.55, P < 0.0003). Myocyte
      area also correlated positively with FI (r = 0.34, P = 0.03). Left ventricular
      developed pressure (LVDP) plus rates of pressure development (+dP/dt) and decay (
      dP/dt) declined with age and this was graded by frailty (r = -0.51, P = 0.0007; r
      = -0.48, P = 0.002; r = -0.56, P = 0.0002 for LVDP, +dP/dt and -dP/dt). Smaller,
      slower contractions graded by FI score were also seen in ventricular myocytes.
      Contractile dysfunction in cardiomyocytes isolated from frail mice was
      attributable to parallel changes in underlying Ca2+ transients. These changes
      were not due to reduced sarcoplasmic reticulum stores, but were graded by smaller
      Ca2+ currents (r = -0.40, P = 0.008), lower gain (r = -0.37, P = 0.02) and
      reduced expression of Cav1.2 protein (r = -0.68, P = 0.003). These results show
      that cardiac hypertrophy and contractile dysfunction in naturally aging mice are
      graded by overall health and suggest that frailty, in addition to chronological
      age, can help explain heterogeneity in cardiac aging.

PMID- 28502097
TI  - Oral health-related quality of life and risk factors associated with traumatic
      dental injuries in Brazilian children: A multilevel approach.
AB  - BACKGROUND/AIMS: Among the diseases related to oral health, such as caries and
      oral cancer, dental trauma stands out as one of the major public health problems
      worldwide. The aim of this study was to verify the occurrence of factors
      associated with traumatic dental injuries (TDIs), including oral health-related
      quality of life (OHRQoL), sociodemographic characteristics, untreated caries,
      occlusal problems and contextual variables in 12-year-old Brazilian children.
      METHODS: This study assessed a complex sample of the National Research in Oral
      Health (SBBrasil 2010) data on 7240 12-year-old children and contextual features
      of the municipalities where they lived. RESULTS: TDI prevalence in 12-year-old
      schoolchildren was 23.96%. Being female was a protective factor for all trauma
      outcome variables. Non-white children were at risk of maxillary tooth fractures.
      Maxillary overjet greater than 3 mm was associated with all trauma outcomes.
      Crowding and spacing were risk factors for enamel trauma. TDI has a negative
      impact on OHRQoL. None of the contextual variables analysed (Gini coefficient,
      MHDI, family health strategy and water fluoridation) were associated with TDI in
      the multilevel approach. CONCLUSIONS: TDI was better explained by individual
      factors, related to sociodemographic conditions and occlusal problems, with a
      negative impact on OHRQoL, adjusted for untreated caries. Contextual variables
      were not associated with TDI in 12-year-old Brazilian schoolchildren.
      Interdisciplinary actions for preventing dental trauma, such as stimulating the
      use of mouthguards, have to be encouraged by the family health strategy (FHS) and
      school health programme (SHP).

PMID- 28502098
TI  - "Fix Me Another Marguerite!": Species delimitation in a group of intensively
      hybridizing lineages of ox-eye daisies (Leucanthemum Mill., Compositae
      Anthemideae).
AB  - Delineating species boundaries in the framework of the multi-species coalescent
      (MSC) proves to be a reliable, objective, and reproducible method in an
      increasing number of studies. However, the underlying model assumes the lack of
      gene flow after speciation; an assumption which may be frequently violated in
      plant evolution. This study evaluates the robustness of currently available
      species delimitation methods implemented in beast (BFD, BFD*, and dissect) in the
      closely-knit ox-eye daisy group around Leucanthemum ageratifolium Pau. Comprising
      five taxa being allopatrically distributed between northern Spain and southern
      Italy this study group shows signs of hybridization with the widespread and
      codistributed species Leucanthemum vulgare (Vaill.) Lam. to various extent. As
      expected, our empirical analyses based on both AFLP fingerprinting and sequence
      data demonstrate that the robustness of species delimitation results is
      considerably influenced by the intensity of hybridization among species and the
      number of hybrid individuals included. Therefore, we set up a methodological
      pipeline with a first step of identification and subsequent removal of
      individuals showing admixed genetic patterns caused by actual interbreeding using
      AFLP-fingerprint and morphometric data, followed by application of different
      Bayesian MSC species delimitation methods based on the remnant individuals using
      both AFLP-fingerprint and sequence data (four nuclear markers, five concatenated
      intergenic spacer regions of the plastid genome). The results argue for
      acknowledgement of Leucanthemum laciniatum, L. legraeanum, and L. ligusticum as
      independent species, show the close relationship of L. ageratifolium, L.
      monspeliense, and L. vulgare, and give rise to the description of three
      nothospecies new to science.

PMID- 28502100
TI  - HER2 FISH results in breast cancers with increased CEN17 signals using
      alternative chromosome 17 probes - reclassifying cases in the equivocal category.
AB  - AIMS: HER2 testing of invasive breast cancer by in-situ hybridization guides
      therapy decisions. Probing HER2 and centromere of chromosome 17 (cen17)
      simultaneously is supposed to reveal both a potential HER2 gene amplification and
      polysomy 17. However, a considerable number of breast cancer patients with quasi
      polysomy 17 are considered 'equivocal', which is diagnostically meaningless.
      Moreover, patients with equivocal/false polysomic tumours are prevented from a
      potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122
      and TP53 hybridization markers to indicate true polysomy reliably and to
      reclassify equivocal samples accurately as HER2-positive. METHODS AND RESULTS:
      Samples with (n = 82) and without (n = 52) increased cen17 copy numbers and 78
      evidently HER2-amplified specimens were analysed using dual and triple marker
      hybridization probes. Selected putative polysomic samples were subjected to array
      based comparative genomic hybridization (aCGH). We found that 37.8% samples with
      putative polysomy 17 did not show any gain in RAI1, D17S122 or TP53. Accordingly,
      aCGH revealed evidence for the presence of HER2/cen17 co-amplification rather
      than for true polysomy in those cases. Reflex testing using alternate 17p markers
      reclassified up to 56.3% equivocal cases as HER2-positive and the combined
      assessment of a 17p and 17q locus allows the differentiation of true versus false
      polysomy. CONCLUSIONS: An increased cen17 copy number does not necessarily
      reflect polysomy, and reflex testing facilitates the reclassification of
      'equivocals'. Nevertheless, the prognostic and predictive value of a HER2/cen17
      co-amplification versus HER2 gene amplification alone must still be evaluated
      prospectively.

PMID- 28502099
TI  - International trends in clozapine use: a study in 17 countries.
AB  - OBJECTIVE: There is some evidence that clozapine is significantly underutilised.
      Also, clozapine use is thought to vary by country, but so far no international
      study has assessed trends in clozapine prescribing. Therefore, this study aimed
      to assess clozapine use trends on an international scale, using standardised
      criteria for data analysis. METHOD: A repeated cross-sectional design was applied
      to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014,
      overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons)
      and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100
      000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014,
      clozapine use increased in almost all studied countries (relative increase: 7.8
      197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range:
      0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years),
      clozapine use was highest in Finland (24.7/100 000) and in the publicly insured
      US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most
      studied countries over recent years, clozapine is still underutilised in many
      countries, with clozapine utilisation patterns differing significantly between
      countries. Future research should address the implementation of interventions
      designed to facilitate increased clozapine utilisation.

PMID- 28502101
TI  - Identification of somatic TERT promoter mutations in familial nonmedullary
      thyroid carcinomas.
AB  - OBJECTIVE: The genes causing familial nonmedullary thyroid carcinoma (FNMTC)
      identified to date are only involved in a small fraction of the families.
      Recently, somatic mutations in TERT promoter region and in EIF1AX gene were
      reported in thyroid tumours of undefined familial status. The aim of this study
      was to investigate the role of TERT and EIF1AX mutations in familial thyroid
      tumours. DESIGN: The promoter region of TERT was sequenced in leucocyte DNA of
      the probands from 75 FNMTC families. In thyroid tumours from 54 familial cases,
      we assessed somatic TERT promoter, RAS and BRAF hotspot mutations, and the whole
      EIF1AX gene. RESULTS: No potentially pathogenic germline variants were identified
      in TERT in the 75 FNMTC families' probands. In the 54 carcinomas, we identified
      five cases (9%) with hotspot somatic TERT promoter mutations. BRAF mutations were
      found in 41% of the tumours. All TERT-positive samples were also positive for
      BRAF p.Val600Glu, and this co-occurrence was found to be statistically
      significant (P=.008). RAS mutations were detected in four tumours wild-type for
      TERT (7%). Evaluation of tumour mutation data together with the patients'
      clinicopathological features revealed a significant correlation between TERT plus
      BRAF mutations and advanced tumour stage (T4) (P=.020). No mutations were
      identified in EIF1AX. CONCLUSIONS: The results of this study suggest that TERT
      promoter and EIF1AX mutations are not frequently involved in FNMTC aetiology.
      However, we show for the first time that TERT alterations are associated with
      familial thyroid tumour progression. Our data also suggest that TERT mutations
      are more often found in concomitance with BRAF mutations in advanced stages of
      FNMTC.

PMID- 28502102
TI  - Functional analysis by minigene assay of putative splicing variants found in
      Bardet-Biedl syndrome patients.
AB  - Bardet-Biedl syndrome (BBS) and Alstrom syndrome (ALMS) are rare diseases
      belonging to the group of ciliopathies. Although mutational screening studies of
      BBS/ALMS cohorts have been extensively reported, little is known about the
      functional effect of those changes. Thus, splicing variants are estimated to
      represent 15% of disease-causing mutations, and there is growing evidence that
      many exonic changes are really splicing variants misclassified. In this study, we
      aimed to analyse for the first time several variants in BBS2, ARL6/BBS3, BBS4 and
      ALMS1 genes predicted to produce aberrant splicing by minigene assay. We found
      discordance between bioinformatics analysis and experimental data when comparing
      wild-type and mutant constructs. Remarkably, we identified nonsense variants
      presumably resistant to nonsense-mediated decay, even when a premature
      termination codon would be introduced in the second amino acid (p.(G2*) mutation
      in ARL6/BBS3 gene). As a whole, we report one of the first functional studies of
      BBS/ALMS1 variants using minigene assay, trying to elucidate their role in
      disease. Functional studies of variants identified in BBS and ALMS patients are
      essential for their proper classification and subsequent genetic counselling and
      could also be the start point for new therapeutic approaches, currently based
      only on symptomatic treatment.

PMID- 28502103
TI  - Reduced platelet aggregation in women after intercourse: a possible role for the
      cyclooxygenase pathway.
AB  - We hypothesise that molecules in the cyclooxygenase pathway affect platelet
      activity when seminal fluid (SF) is present. We considered the influence of SF on
      platelet aggregation in women, and believe that the prostanoids in SF signalling
      are significant. Thirty-one female subjects were studied, 20 of whom were
      sexually active. Male partners were given either aspirin or indomethacin to
      inhibit cyclooxygenase. The 6-keto prostaglandin F1alpha (6-keto PGF1alpha) and
      prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay.
      Platelets and prostanoids were evaluated in women, periodically, before and after
      intercourse. The platelets were tested with adenosine diphosphate (ADP) and
      arachidonic acid (AA). To block the interaction between the uterus and SF, some
      couples used condoms. We found that the 6-keto prostaglandin F1alpha in urine at
      2 hours post-intercourse (1418.75 pg/mL, Std 688.39) was greater than pre
      intercourse (772.68 pg/mL, Std 116.54). Post-intercourse, a transient decrease in
      platelet aggregation was observed in women whose partners did not use condoms.
      Averages for platelet aggregation were 20.16% with ADP, and more significantly,
      37.79% with AA after 2 hours. In contrast, couples using condoms showed no
      changes, averaging 64.02% with ADP and 72.06% with AA. Women whose partners were
      taking aspirin or indomethacin also showed no changes. SF from men taking aspirin
      or indomethacin led to no reduction in platelet aggregometry in their partners.
      These results indicate that in cases of exposure to SF, the transient change in
      women's platelet activity could be related to the cyclooxygenase pathway.

PMID- 28502104
TI  - Assessing Pain Intensity Using Photoplethysmography Signals in Chronic Myofascial
      Pain Syndrome.
AB  - BACKGROUND: Efficacy of pain assessment is the basis for effective therapy.
      Clinically, assessing pain is by subjective scale, but these methods have some
      shortcomings. Therefore, studies have been conducted on assessment of pain using
      physiological signals. Photoplethysmography (PPG) signals provide much
      information about the cardiovascular system. PPG-derived parameters (PPG
      parameters) reflect nociceptive stimulation, and obtain an approximation of the R
      R interval from the PPG period. The aim of this study was to evaluate PPG signals
      for assessment of pain intensity in chronic myofascial pain syndrome (MPS)
      patients. METHODS: This study recruited 37 patients with chronic MPS; all of them
      were treated with electrotherapy and thermotherapy. The difference between pre-
      and post-therapy PPG parameters, and the correlation between pulse rate
      variability (PRV) and heart rate variability (HRV) were determined. We also
      obtained patients' pain intensity scores by visual analog scale, visual rating
      scale, and Wong-Banker face pain rating scale. RESULTS: Photoplethysmography and
      PRV/HRV parameters showed significant differences between pre- and post
      treatment. The variation trend of PRV was similar with HRV in heart rate, R-R
      interval, low frequency, high frequency, and LF/HF; in addition, a high
      correlation between the parameters was observed either in pre- or post-therapy.
      PPG parameters indicated increased sympathetic tone. CONCLUSION: The results of
      the study indicated that PRV substituted for HRV in assessment of pain intensity
      in chronic MPS reflected parasympathetic nervous tone increase, and PPG
      parameters might reflect stress stimulation on skin.

PMID- 28502106
TI  - Misoprostol for cervical priming prior to office hysteroscopy works in
      premenopausal nulliparous but not in postmenopausal women.

PMID- 28502105
TI  - Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.
AB  - CONTEXT: While the prevalence of vitamin D deficiency is well described in
      various populations, limited data are available regarding longitudinal variation
      in serum 25-hydroxyvitamin D concentrations. OBJECTIVES: To evaluate the temporal
      trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors
      influencing these trends. PARTICIPANTS, DESIGN AND SETTING: Adults enrolled in
      the Dallas Heart Study, a longitudinal, probability-based, multiethnic,
      population study in Dallas, Texas, USA. MAIN OUTCOME MEASURES: Prevalence of
      vitamin D deficiency and predictors of change in serum 25(OH)D. RESULTS: A total
      of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and
      2007-2009) at a median interval of 7 years. Serum 25(OH)D decreased (42.7-39.4
      nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50 nmol/L]
      increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation
      increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model
      adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a
      greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs 
      3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black
      ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0 nmol/L,
      P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7 nmol/L,
      P=.032). CONCLUSIONS: Despite increased vitamin D supplementation, serum 25(OH)D
      decreased in an ethnically diverse cohort of Dallas County residents between 2000
      2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D
      include male sex, Hispanic ethnicity and weight gain.

PMID- 28502107
TI  - A nano particle vector comprised of poly lactic-co-glycolic acid and
      monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis
      peptides stimulate a pro-immune profile in bovine macrophages.
AB  - AIMS: We evaluated the potential of a nanoparticle (NP) delivery system to
      improve methods of delivery of candidate peptide-based vaccines for
      Paratuberculosis in cattle. METHODS AND RESULTS: Peptides derived from
      Mycobacterium avium subsp. paratuberculosis (Map), and the pro-inflammatory
      monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly
      (d,l-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with
      macrophages to examine their effects on survival and function. PLGA/MPLA NPs,
      with and without Map antigens, are efficiently phagocytized by macrophages with
      no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of
      expression of MHC I or II molecules. Expression of TNFalpha and IL12p40 was
      increased in Map-loaded NPs. T-cell proliferation studies using a model peptide
      from Anaplasma marginale demonstrated that a CD4 T-cell recall response could be
      elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA
      NP. CONCLUSIONS: These findings indicate PLGA/MPLA NPs can be used as a vehicle
      for delivery and testing of candidate peptide-based vaccines. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These results will assist on more in depth studies on PLGA
      NP delivery systems that may lead to the development of a peptide-based vaccine
      for cattle.

PMID- 28502110
TI  - A novel frameshift mutation of the ADAR1 gene in a Chinese patient with
      dyschromatosis symmetrica hereditaria and the dermoscopic features.

PMID- 28502108
TI  - Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in
      infancy: A birth cohort study.
AB  - BACKGROUND: Filaggrin gene (FLG) expression, particularly in the skin, has been
      linked to the development of the skin barrier and is associated with eczema risk.
      However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is
      associated with eczema development and prediction is lacking. OBJECTIVE: This
      study sought to assess whether FLG expression in UCB associates with and predicts
      the development of eczema in infancy. METHODS: Infants enrolled in a birth cohort
      study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes
      measuring FLG transcripts expression in UCB were available from genomewide gene
      expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were
      genotyped. Associations were assessed using Poisson regression with robust
      variance estimation. Area under the curve (AUC), describing the
      discriminatory/predictive performance of fitted models, was estimated from
      logistic regression. RESULTS: Increased level of FLG expression measured by probe
      A_24_P51322 was associated with reduced risk of eczema during the first year of
      life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense
      transcripts measured by probe A_21_P0014075 was associated with increased risk of
      eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG
      expression, FLG genetic variants, and sex, discrimination between children who
      will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI:
      0.84-0.98). CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated, for the
      first time, that FLG expression in UCB is associated with eczema development in
      infancy. Moreover, our analysis provided prediction models that were capable of
      discriminating, to a great extent, between those who will and will not develop
      eczema in infancy. Therefore, early identification of infants at increased risk
      of developing eczema is possible and such high-risk newborns may benefit from
      early stratification and intervention.

PMID- 28502109
TI  - Reproductive performance of resident and migrant males, females and pairs in a
      partially migratory bird.
AB  - Quantifying among-individual variation in life-history strategies, and associated
      variation in reproductive performance and resulting demographic structure, is key
      to understanding and predicting population dynamics and life-history evolution.
      Partial migration, where populations comprise a mixture of resident and
      seasonally migrant individuals, constitutes a dimension of life-history variation
      that could be associated with substantial variation in reproductive performance.
      However, such variation has rarely been quantified due to the challenge of
      measuring reproduction and migration across a sufficient number of seasonally
      mobile males and females. We used intensive winter (non-breeding season)
      resightings of colour-ringed adult European shags (Phalacrocorax aristotelis)
      from a known breeding colony to identify resident and migrant individuals. We
      tested whether two aspects of annual reproductive performance, brood hatch date
      and breeding success, differed between resident and migrant males, females and
      breeding pairs observed across three consecutive winters and breeding seasons.
      The sex ratios of observed resident and migrant shags did not significantly
      differ from each other or from 1:1, suggesting that both sexes are partially
      migratory and that migration was not sex-biased across surveyed areas. Individual
      resident males and females hatched their broods 6 days earlier and fledged 0.2
      more chicks per year than migrant males and females on average. Resident
      individuals of both sexes therefore had higher breeding success than migrants.
      Hatch date and breeding success also varied with a pair's joint migratory
      strategy such that resident-resident pairs hatched their broods 12 days earlier
      than migrant-migrant pairs, and fledged 0.7 more chicks per year on average.
      However, there was no evidence of assortative pairing with respect to migratory
      strategy: observed frequencies of migrant-migrant and resident-resident pairs did
      not differ from those expected given random pairing. These data demonstrate
      substantial variation in two key aspects of reproductive performance associated
      with the migratory strategies of males, females and breeding pairs within a
      partially migratory population. These patterns could reflect direct and/or
      indirect mechanisms, but imply that individual variation in migratory strategy
      and variation in pairing among residents and migrants could influence selection
      on migration and drive complex population and evolutionary dynamics.

PMID- 28502111
TI  - Upregulation of ASAP3 contributes to colorectal carcinogenesis and indicates poor
      survival outcome.
AB  - The function and clinical implication of ArfGAP with SH3 domain, ankyrin repeat,
      and PH domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the
      present study, we showed that the expression level of ASAP3 was dramatically
      increased in CRC and its upregulation was associated with American Joint
      Committee on Cancer stage (P < 0.001) and poor prognosis (P = 0.0022). The
      combination of stage and ASAP3 expression improved the prediction of survival in
      CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1
      phase arrest without influencing apoptosis. ASAP3 promoted growth of colon tumors
      in mice with colitis, and accelerated cell invasion and migration in vitro.
      Increased ASAP3 was associated with activation of the nuclear factor-kappaB (NF
      kappaB) canonical pathway in CRC. Upregulation of ASAP3 increased the
      phosphorylation and nuclear translocation of the p65 NF-kappaB subunit.
      Mechanistically, ASAP3 interacts with NF-kappaB essential modulator (NEMO) and
      could reduce the polyubiquitinylation of NEMO. Overall, ASAP3 might regulate NF
      kappaB via binding to NEMO. ASAP3 acts as an oncogene in colonic cancer and could
      be a potential biomarker of colon carcinogenesis.

PMID- 28502112
TI  - Sodium-glucose cotransporter-2 inhibitor luseogliflozin added to glucagon-like
      peptide 1 receptor agonist liraglutide improves glycemic control with bodyweight
      and fat mass reductions in Japanese patients with type 2 diabetes: A 52-week,
      open-label, single-arm study.
AB  - AIMS/INTRODUCTION: The aim of the present study was to evaluate the safety and
      efficacy of luseogliflozin added to liraglutide monotherapy in Japanese
      individuals with type 2 diabetes. MATERIALS AND METHODS: This 52-week,
      multicenter, open-label, single-arm clinical study enrolled Japanese patients who
      had inadequate glycemic control with diet/exercise and liraglutide monotherapy.
      Major efficacy end-points included the changes from baseline in glycated
      hemoglobin, fasting plasma glucose and bodyweight. Body composition was also
      assessed in individuals who had access to bioelectrical impedance analysis.
      Safety assessments included adverse events, clinical laboratory tests, vital
      signs and 12-lead electrocardiograms. RESULTS: Of 76 patients who received
      luseogliflozin, 62 completed the study. The changes from baseline in glycated
      hemoglobin, fasting plasma glucose, and bodyweight (mean +/- SE) were -0.68 +/-
      0.10%, -32.1 +/- 3.6 mg/dL and -2.71 +/- 0.24 kg at week 52, respectively (all, P
      < 0.001 vs baseline). Luseogliflozin was associated with greater reductions in
      fat mass than lean mass at all measuring points (n = 22): fat vs lean mass
      changes (mean +/- SE) at week 52 were -2.49 +/- 0.45 kg (P < 0.001 vs baseline)
      and -0.44 +/- 0.26 kg (P = 0.107 vs baseline), respectively. Insulin secretion
      and Matsuda Index were also improved at weeks 12 and 52 compared with baseline.
      Adverse events and adverse drug reactions occurred in 65.8 and 27.6% of patients,
      respectively. The overall safety profile, including frequency of hypoglycemia,
      was found to be consistent with those of previous studies and there were no new
      safety concerns. CONCLUSIONS: Luseogliflozin added to liraglutide was well
      tolerated, and improved glycemic control with bodyweight and fat mass reductions
      in Japanese type 2 diabetes patients.

PMID- 28502114
TI  - Risk factors for executive function difficulties in preschool and early school
      age preterm children.
AB  - AIM: To investigate the relationship between executive functioning and social and
      perinatal risk factors in four- to five-year-old preterm children. METHODS: Using
      standardised measures of general intelligence and performance-based executive
      function (EF) tests prior to starting kindergarten, 141 children born preterm
      (<33 weeks of gestation) and 77 term comparison children were assessed. Parental
      and teacher reports of executive functioning were completed when the children
      commenced kindergarten. The preterm and the term comparison groups were compared
      on measures of intelligence and EFs using independent-groups t-tests, and
      multivariate regression analyses were performed to identify factors predictive of
      intelligence and executive functioning in the preterm group. RESULTS: The preterm
      group performed significantly more poorly than the comparison group on all
      intelligence and EF tests. The parental reports of the preterm and term
      comparison children's EF did not differ significantly, but the teachers reported
      elevated EF difficulties for the preterm group. Higher social risk, in particular
      lower educational level of the main caregiver, was the strongest predictor for
      the preterm children's intelligence and EF results. CONCLUSION: Social risk
      factors are strongly associated with impaired early EF outcomes in preterm
      children.

PMID- 28502116
TI  - Phenolic Composition, Anti-Inflammatory, Antioxidant, and Antimicrobial
      Activities of Alchemilla mollis (Buser) Rothm.
AB  - The current study was designed to evaluate the antioxidant, anti-inflammatory and
      antimicrobial activities of Alchemilla mollis (Buser) Rothm. (Rosaceae) aerial
      parts extracts. Chemical composition was analyzed by spectrophotometric and
      chromatographic (HPLC) techniques. The antioxidant properties assessed included
      DPPH. and ABTS.+ radical scavenging, beta-carotene-linoleic acid co-oxidation
      assay. Antimicrobial activity was evaluated with disc diffusion and micro
      dilution method. In order to evaluate toxicity of the extracts, with the
      sulforhodamine B colorimetric assay L929 cell line (mouse fibroblast) was used.
      The anti-inflammatory activities of the potent antioxidant extracts (methanol,
      70% methanol, and water extracts) were determined by measuring the inhibitory
      effects on NO production and pro-inflammatory cytokine TNF-alpha levels in
      lipopolysaccharide stimulated RAW 264.7 cells. 70% methanol and water extracts
      which were found to be rich in phenolic compounds (184.79 and 172.60 mg GAE/g
      extract) showed higher antioxidant activity. Luteolin-7-O-glucoside was the main
      compound in the extracts. Ethyl acetate and 70% methanol extracts showed higher
      antibacterial activity against Staphylococcus aureus and Salmonella enteritidis
      with MIC value of 125 MUg/ml. 70% methanol extract potentially inhibited the NO
      and TNF-alpha production (18.43 MUm and 1556.22 pg/ml, respectively, 6 h).

PMID- 28502115
TI  - Use of the 10-Group Classification System to analyze how the population control
      policy change in China has affected cesarean delivery.
AB  - OBJECTIVE: To analyze the initial effect following the relaxation of China's
      population control policy on the cesarean delivery (CD) rate using the 10-Group
      Classification System (TGCS). METHODS: A retrospective study included all
      deliveries at a center in Nanjing, China, during 2014-2015. The deliveries were
      classified using the TGCS. The obstetric populations and the CD rates in each
      group were compared between 2014 and 2015. RESULTS: Overall, 11 006 deliveries
      were analyzed. The overall CD rate increased from 28.3% (1623/5737) in 2014 to
      33.8% (1782/5269) in 2015 (P<0.001). The largest contributor to the overall CD
      rate-accounting for approximately one-third of all CDs-were nulliparous women
      with a single cephalic term pregnancy and induced labor or prelabor CD (group 2);
      the CD rate in this group increased from 27.2% to 31.4%. Moreover, the proportion
      of women with a single cephalic term pregnancy with previous CD (group 5) steeply
      increased from 6.4% to 10.4% of all deliveries; the CD rate in this group during
      2014-2015 was 76.6%. CONCLUSION: With China ending its one-child policy, the
      characteristics of the obstetric population changed. Women with a single cephalic
      term pregnancy with previous CD were the largest contributor to the CD rate
      increase.

PMID- 28502117
TI  - Passive Membrane Penetration of the Serotonin Precursor 5-Hydroxytryptophan is
      Controlled by Its Zwitterion.
AB  - Species-specific partition coefficients in the octanol/water system were
      determined for the neurotransmitter serotonin (5-HT) and its precursor 5
      hydroxytryptophan (5-HTP). The pH-independent partition coefficients (p) of the
      individual microspecies were determined by combination of experimentally measured
      distribution constants and a custom-tailored evaluation method, using highly
      similar auxiliary compounds. Experimental microscopic partition coefficients for
      triprotic molecules have only been reported before for thyroxine and its
      derivatives. The parabolic pH-distribution profile of 5-HT shows the dominance of
      the lipophilic non-charged microspecies, with a log p of 0.66. However, the most
      lipophilic non-charged form of 5-HTP, with a log p of 0.31, has no significant
      contribution to the distribution coefficient at any pH value. Instead, the less
      lipophilic zwitterionic protonation isomer dominates the distribution in the pH
      range 2.10 - 11.11. Although the non-charged microspecies of 5-HTP is 151 times
      more lipophilic than its zwitterionic protonation isomer, the overwhelming
      dominance of the zwitterionic form ensures that its contribution to the overall
      lipophilicity exceeds 1320 times that of the non-charged one. This fact is
      another counter-example of the widespread belief that passive diffusion into
      lipophilic media is predominated by the non-charged species. The lipophilicity
      profile of 5-HT and 5-HTP is depicted in terms of species-specific
      lipophilicities.

PMID- 28502113
TI  - Epigenetic modifications of the VH region after DJH recombination in Pro-B cells.
AB  - The variable region of murine immunoglobulin heavy chain (Igh) is assembled by
      sequential DH -JH and VH -DJH recombination. The accessibility of the Igh locus
      determines the order of rearrangement. Because of the large number of VH genes
      and the lack of a suitable model, the epigenetic modifications of VH genes after
      DJH recombination have not previously been characterized. Here, we employed two v
      Abl pro-B cell lines, in which the Igh locus is in germline and DJH -recombined
      configurations, respectively. The DJH junction displays the characteristics of a
      recombination centre, such as high levels of activation-associated histone
      modifications and recombination-activating gene protein (RAG) binding in DJH 
      rearranged pro-B cells, which extend the recombination centre model proposed for
      the germline Igh locus. The different domains of the VH region have distinct
      epigenetic characteristics after DJH recombination. Distal VH genes have higher
      levels of active histone modifications, germline transcription and Pax5 binding,
      and good quality recombination signal sequences. Proximal VH genes are relatively
      close to the DJH recombination centre, which partially compensates for the low
      levels of the above active epigenetic modifications. DJH recombination centre
      might serve as a cis-acting element to regulate the accessibility of the VH
      region. Furthermore, we demonstrate that RAG weakly binds to functional VH genes,
      which is the first detailed assessment of RAG dynamic binding to VH genes. We
      provide a way for VH -DJH recombination in which the VH gene is brought into
      close proximity with the DJH recombination centre for RAG binding by a Pax5
      dependent chromosomal compaction event, and held in this position for subsequent
      cleavage and VH -DJH joining.

PMID- 28502119
TI  - Neutrophil-to-lymphocyte ratio decreases after treatment of psoriasis with
      therapeutic antibodies.

PMID- 28502118
TI  - The role of rare morph advantage and conspicuousness in the stable gold-dark
      colour polymorphism of a crater lake Midas cichlid fish.
AB  - Genetically based stable colour polymorphisms provide a unique opportunity to
      study the evolutionary processes that preserve genetic variability in the wild.
      Different mechanisms are proposed to promote the stability of polymorphisms, but
      only few empirical examples have been documented, resulting in an incomplete
      understanding of these mechanisms. A remarkable genetically determined stable
      colour polymorphism is found in the Nicaraguan Midas cichlid species complex
      (Amphilophus cf. citrinellus). All Midas cichlids start their life with a dark
      grey coloration (dark morph), but individuals carrying the dominant "gold" allele
      (c. 10%) lose their melanophores later in life, revealing the underlying orange
      coloration (gold morph). How this polymorphism is maintained remains unclear. Two
      main hypotheses have been proposed, both suggesting differential predation upon
      colour morphs as the proximate mechanism. One predicts that the conspicuous gold
      morph is more likely to be preyed upon, but this disadvantage is balanced by
      their competitive dominance over the dark morph. The second hypothesis suggests a
      rare morph advantage where the rarer gold morph experiences less predation.
      Empirical evidence for either of these mechanisms is still circumstantial and
      inconclusive. We conducted two field experiments in a Nicaraguan crater lake
      using wax models simulating both morphs to determine predation pressure upon
      Midas cichlid colour morphs. First, we tested the interaction of coloration and
      depth on attack rate. Second, we tested the interaction of fish size and
      coloration. We contrasted the pattern of attacks from these experiments to the
      predicted predation patterns from the hypotheses proposed to explain the colour
      polymorphism's stability. Large models imitating colour morphs were attacked at
      similar rates irrespectively of their position in the water column. Yet, attacks
      upon small models resembling juveniles were directed mainly towards dark models.
      This resulted in a significant size-by-colour interaction. We suggest that gold
      Midas cichlids experience a rare morph advantage as juveniles when individuals of
      this morph are extremely uncommon. But this effect is reduced or disappears among
      adults, where gold individuals are relatively more common. Thus, the interaction
      of rare morph advantage and conspicuousness, rather than either of those factors
      alone, is a likely mechanism resulting in the stability of the colour
      polymorphism in Midas cichlids.

PMID- 28502120
TI  - Gut microbial communities of American pikas (Ochotona princeps): Evidence for
      phylosymbiosis and adaptations to novel diets.
AB  - Gut microbial communities provide many physiological functions to their hosts,
      especially in herbivorous animals. We still lack an understanding of how these
      microbial communities are structured across hosts in nature, especially within a
      given host species. Studies on laboratory mice have demonstrated that host
      genetics can influence microbial community structure, but that diet can overwhelm
      these genetic effects. We aimed to test these ideas in a natural system, the
      American pika (Ochotona princeps). First, pikas are high-elevation specialists
      with significant population structure across various mountain ranges in the USA,
      allowing us to investigate whether similarities in microbial communities match
      host genetic differences. Additionally, pikas are herbivorous, with some
      populations exhibiting remarkable dietary plasticity and consuming high levels of
      moss, which is exceptionally high in fibre and low in protein. This allows us to
      investigate adaptations to an herbivorous diet, as well as to the especially
      challenging diet of moss. Here, we inventoried the microbial communities of pika
      caecal pellets from various populations using 16S rRNA sequencing to investigate
      structuring of microbial communities across various populations with different
      natural diets. Microbial communities varied significantly across populations, and
      differences in microbial community structure were congruent with genetic
      differences in host population structure, a pattern known as "phylosymbiosis."
      Several microbial members (Ruminococcus, Prevotella, Oxalobacter and Coprococcus)
      were detected across all samples, and thus likely represent a "core microbiome."
      These genera are known to perform a number of services for herbivorous hosts such
      as fibre fermentation and the degradation of plant defensive compounds, and thus
      are likely important for herbivory in pikas. Moreover, pikas that feed on moss
      harboured microbial communities highly enriched in Melainabacteria. This
      uncultivable candidate phylum has been proposed to ferment fibre for herbivores,
      and thus may contribute to the ability of some pika populations to consume high
      amounts of moss. These findings demonstrate that both host genetics and diet can
      influence the microbial communities of the American pika. These animals may be
      novel sources of fibre-degrading microbes. Last, we discuss the implications of
      population-specific microbial communities for conservation efforts in this
      species.

PMID- 28502121
TI  - Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy.

PMID- 28502124
TI  - Poster Presentations.

PMID- 28502126
TI  - Program Summary.

PMID- 28502123
TI  - Novel method for the depletion of cariogenic bacteria using dextranomer
      microspheres.
AB  - Streptococcus mutans is recognized as one of the key contributors to the
      dysbiotic state that results in dental caries. Existing treatment strategies
      reduce the incidence of tooth decay, but they also eliminate both the cariogenic
      and beneficial microbes. Here we introduce a novel treatment alternative using
      Sephadex, cross-linked dextranomer microspheres (DMs), typically used for gel
      filtration chromatography. In addition DM beads can be used for affinity
      purification of glucosyltransferases (GTFs) from S. mutans. In this study we take
      advantage of the native pathogenic mechanisms used by S. mutans to adhere, form a
      biofilm and induce dental caries through the expression of surface-associated
      GTFs. We demonstrate that planktonic and biofilm-grown (adhered to hydroxyapatite
      coated pegs to mimic the tooth surface) S. mutans, specifically and competitively
      attach to DMs. Further investigation demonstrated that DMs are a specific
      affinity resin for S. mutans and other cariogenic/pathogenic oral streptococci,
      whereas other commensal and probiotic strains failed to readily adhere to DMs.
      Using antimicrobial cargo loaded into the DM lumen, we demonstrate that when in
      co-culture with non-binding to even modestly binding commensal species, S. mutans
      was selectively killed. This proof of concept study introduces a novel means to
      safely and effectively reduce the pool of S. mutans and other pathogenic
      streptococci in the oral cavity with limited disturbance of the necessary
      commensal (healthy) microbiota when compared with current oral healthcare
      products.

PMID- 28502122
TI  - Humanized NOG mice as a model for tuberculosis vaccine-induced immunity: a
      comparative analysis with the mouse and guinea pig models of tuberculosis.
AB  - The humanized mouse model has been developed as a model to identify and
      characterize human immune responses to human pathogens and has been used to
      better identify vaccine candidates. In the current studies, the humanized mouse
      was used to determine the ability of a vaccine to affect the immune response to
      infection with Mycobacterium tuberculosis. Both human CD4+ and CD8+ T cells
      responded to infection in humanized mice as a result of infection. In humanized
      mice vaccinated with either BCG or with CpG-C, a liposome-based formulation
      containing the M. tuberculosis antigen ESAT-6, both CD4 and CD8 T cells secreted
      cytokines that are known to be required for induction of protective immunity. In
      comparison to the C57BL/6 mouse model and Hartley guinea pig model of
      tuberculosis, data obtained from humanized mice complemented the data observed in
      the former models and provided further evidence that a vaccine can induce a human
      T-cell response. Humanized mice provide a crucial pre-clinical platform for
      evaluating human T-cell immune responses in vaccine development against M.
      tuberculosis.

PMID- 28502129
TI  - Diagnostic Role of RASSF1A and p16INK4a Promoter Gene Hypermethylation in Serum
      DNA of Lung Cancer Patients: Clinicopathological Significance.
AB  - The most common inactivation mechanism of tumor suppressor genes, RASSF1A and
      p16INK4a, in lung cancer is hypermethylation. We detected the methylation status
      of RASSF1A and p16INK4a in serum of lung cancer patients using methylation
      specific PCR and analyzed their clinicopathological significance. Each of RASSF1A
      and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in
      benign lung lesion patients. Hypermethylation was preferentially observed in
      small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a. In non
      small cell lung cancer (NSCLC), RASSF1A and p16INK4a hypermethylation were found
      in 27% and 37.8% respectively. Hypermethylation of RASSF1A was not correlated
      with clinicopathological character. While, p16INK4a hypermethylation was
      associated with age >60 years, smoking and squamous cell carcinoma (SCC) (P =
      0.033), but not with gender and pathological stages of NSCLC. Sensitivity and
      specificity of each gene were 31.1% and 100% respectively and the sensitivity
      improved with evaluation of a combination of the two genes (55.6%). These
      findings suggest that serum RASSF1A and p16INK4a hypermethylation are promising
      diagnostic method for detection of lung cancer. As regard the clinicopathological
      characteristics, p16INK4a hypermethylation may provide a more specific approach
      than RASSF1A hypermethylation.

PMID- 28502130
TI  - Diagnostic and Prognostic Values of Monocyte Chemotactic Protein-1 in Ascitic
      Fluid of Patients with Spontaneous Bacterial Peritonitis.
AB  - Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhotics
      with ascites. Monocyte chemotactic protien-1 (MCP-1) is a chemotactic factor for
      monocytes/macrophages, and it activates lymphocytes and neutrophils during
      infection. This study aimed to evaluate the role of MPC-1 in the pathogenesis of
      SBP and assess its prognostic value and correlation to disease severity. The
      study included ninety patients with liver cirrhosis and ascites. Patients were
      divided into 2 groups: Group I including 45 ascetic patients with SBP (polymorph
      nuclear cell count (PMN) >= 250 cell/mm3 in ascitic fluid), and Group II
      including 45 ascetic patients without SBP. Assessment of the severity of liver
      cirrhosis was done using the modified Child-Pugh and model for end stage liver
      disease (MELD) scores. Ascetic fluid samples were subjected to total leucocytic
      count and differential, albumin, protein, glucose, and serum-ascetic albumin
      gradient analysis Ascetic fluid levels of (MCP-1was measured by ELISA. Higher
      level was detected in patients with SBP as compared to those without SBP. The
      number of polymorph nuclear cell count (PMN) >= 250 cell/mm3 in ascitic fluid)
      was used as gold standard for diagnosis of SBP. The diagnosis sensitivity and
      specificity of MCP level test were 86.7% and 95.4% respectively at cutoff
      of122.5ng/ml with accuracy 91%. MCP-1 level showed positive significant
      correlation with TLC, PMN leucocytes and MELD score. In conclusion, ascitic fluid
      MCP-1 level could be a reliable test for diagnosis of SBP, and could be used as a
      prognostic marker due to its positive correlation with the severity of liver
      disease.

PMID- 28502128
TI  - Belatacept-Resistant Rejection Is Associated With CD28+ Memory CD8 T Cells.
AB  - Recently, newer therapies have been designed to more specifically target
      rejection in an effort to improve efficacy and limit unwanted toxicity.
      Belatacept, a CD28-CD80/86 specific reagent, is associated with superior patient
      survival and graft function compared with traditional therapy, but its adoption
      as a mainstay immunosuppressive therapy has been tempered by increased rejection
      rates. It is essential that the underlying mechanisms associated with this
      rejection be elucidated before belatacept is more widely used. To that end, we
      designed a study in a nonhuman primate kidney transplant model where animals were
      treated with either a belatacept- or a tacrolimus-based immunosuppressive
      regimen. Interestingly, we found that elevated pretransplant frequencies of CD28+
      CD8+ TEMRA cells are associated with rejection on belatacept but not tacrolimus
      treatment. Further analysis showed that the CD28+ CD8+ TEMRA cells rapidly lose
      CD28 expression after transplant in those animals that go on to reject with the
      allograft infiltrate being predominantly CD28- . These data suggest that CD28+
      memory T cells may be resistant to belatacept, capable of further differentiation
      including loss of CD28 expression while maintaining effector function. The unique
      signaling requirements of CD28+ memory T cells provide opportunities for the
      development of targeted therapies, which may synergize with belatacept to prevent
      costimulation-independent rejection.

PMID- 28502131
TI  - Diagnostic Value of Presepsin in Neonatal Sepsis.
AB  - Presepsin has recently been described as biomarker of sepsis. The aim of this
      study was to investigate the diagnostic accuracy of presepsin in diagnosing
      neonatal sepsis and discriminating sepsis from non-infectious systemic
      inflammatory response syndrome (SIRS). The study included 70 full term neonates
      divided into three groups: 1) Sepsis group (22 patients with clinically suspected
      sepsis and positive blood cultures) 2) Non-infectious SIRS group (28 patients
      with clinically suspected sepsis and persistently negative blood cultures) 3)
      Control group (20 healthy neonates without any clinical signs of infection).
      Plasma presepsin level was measured by chemiluminescent enzyme immunoassay
      (CLEIA) and results were compared with that of C-reactive protein (CRP) assay.
      The results revealed that presepsin levels were significantly higher in sepsis
      group than in non-infectious SIRS group and controls (P <0.001). The area under
      the receiver operating characteristics (ROC) curve (AUC) for discriminating
      sepsis from non-infectious SIRS patients was 0.990 for presepsin and it was
      significantly higher than that of CRP (0.804). The best cut-off value for
      presepsin was 812 pg/ml, which was associated with sensitivity, specificity and
      negative predictive value of 95.5%, 91.7% and 97.8% respectively. In conclusion,
      presepsin is a sensitive and accurate biomarker and is useful for the diagnosis
      of sepsis and discrimination from non-infectious SIRS in neonates.

PMID- 28502132
TI  - Evaluation of Non Invasive versus Invasive Methods for Diagnosis of Helicobacter
      pylori Infection among Patients with Gastroduodenal Disorders.
AB  - H. pylori, a spiral gram-negative bacterium, is associated with gastroduodenal
      diseases. All H. pylori diagnostic assays have limitations. Cytotoxin-associated
      gene A (cag A), a virulence marker, can be identified by PCR. We evaluated H.
      pylori diagnostic methods, invasive: rapid urease test (RUT), and
      histopathological examination (HE), and serology as non-invasive method. Positive
      cases were studied for presence of cag A gene. Upper endoscopies and gastric
      biopsies were performed on 67 dyspeptic patients for RUT, HE and PCR. Anti H.
      pyloriIgG were measured by ELISA. Of 67 dyspeptic patients, 23 (34%) had more
      than one endoscopic finding, 46 (68.7%) were H.pylori positive by HE, and
      21(31.3%) were negative with variable grades of mucosal antral neutrophil
      infiltration. Of the 46 HE positives, PCR detected CagA in 22 (47.8%). Using HE
      as the gold standard test, the sensitivity of ELISA and RUT was 93.48% and
      86.96%, respectively; and the specificity was 85.71% and 47.62%, respectively. In
      conclusion, IgG detection by ELISA is a suitable screening test for diagnosis of
      H. pylori associated gastroduodenal diseases. Histopathology should be performed
      in ELISA negative cases to exclude infection.

PMID- 28502133
TI  - T Regulatory Cells Response to Allergen Specific Immunotherapy in Patients with
      Allergic Airway Diseases: A Prospective Study.
AB  - Forkhead box P3 (FoxP3) T regulatory (Treg) cells modulate the immune system by
      blocking other types of T-cells. They maintain tolerance to self-antigens and
      help in inducing tolerance to foreign antigens. A deregulation of FoxP3 Tregs
      seems to play an important role in allergic disorders. The aim of this work was
      to study the response of FoxP3 Treg cells and their FoxP3 expression in patients,
      attending the Allergy Unit and the Chest Outpatient Clinic, Faculty of Medicine,
      Zagazig University, with allergic airway diseases, before and 1 year after
      receiving subcutaneous allergen specific immunotherapy (SIT). This prospective
      study was carried out on 25 patients with allergic airway diseases, confirmed by
      positive skin test, and that showed clinical improvement one year after SIT. All
      cases were subjected to total immunoglobulin E quantitation by ELISA. FoxP3 Treg
      cells frequency and FoxP3 relative fluorescence intensity, as an indicator of
      Tregs function, were assessed by flowcytometry. The results were compared before
      and after SIT. Twenty five age and sex matched apparently healthy volunteers were
      enrolled as controls. Our findings demonstrated that in comparison to the control
      group, the count of FoxP3 T regulatory cells was higher; however, the function
      was lower among the enrolled patients (P= 0.007 and P< 0.001, respectively). When
      FoxP3 Tregs were compared in the patients before and one year after SIT, it was
      found that both the count and FoxP3 expression showed statistically significant
      increase (P< 0.001). An inverse correlation was found between FoxP3 Tregs count
      and FoxP3 expression. It is concluded that patients with allergic airway diseases
      have increased number of FoxP3 Treg cells but with defective function. SIT plays
      a role in increasing the number of FoxP3 Tregs and improving their suppressive
      function, which leads to control of airway inflammation and thus clinical
      improvement.

PMID- 28502134
TI  - Thyroid Dysfunctions in a Sample of Egyptian Children and Adolescents with
      Systemic Lupus Erythematosus: Relation to Disease Activity and Duration.
AB  - Systemic lupus erythematosus (SLE) is a chronic, autoimmune, inflammatory disease
      affects any organ of the body, including the thyroid gland. Both hypothyroidism
      and hyperthyroidism have been found in SLE patients more frequently than general
      population. The aim of this study was to evaluate the frequency of autoimmune
      thyroid dysfunctions in juvenile SLE and its relation to disease activity and
      duration. A prospective case-control study was carried on 40 children with
      juvenile SLE and 30 healthy as controls, all were subjected to measurement of
      serum TSH, Free T3, Free T4 and anti-TG by ELISA. The SLEDAI scoring system was
      used to evaluate the disease activity. Fourteen patients (35%) demonstrated
      thyroid dysfunctions, in the form of; euthyroid sick syndrome in 6 (15%), overt
      hypothyroidism in 4 (10%), hyperthyroidism in 2 (5%) and subclinical
      hyperthyroidism in 2 cases (5%). Positive anti-TG was detected in 8 cases (20%)
      with a significant (P<0.05) increase in mean levels of serum anti-thyroglobulin
      antibodies in patients (38.25+/-15.224 Iu/ml) as compared to controls (22.79+/
      3.71 Iu/ml). There was a significant positive correlation between SLEDAI and anti
      TG and a significant negative correlation between disease duration and anti-TG,
      TSH In conclusion; thyroid dysfunctions increase in children with SLE patients
      and correlate with severity of the disease.

PMID- 28502135
TI  - Systemic Lupus Erythmatosus is Associated with Disturbed Cytokine Milieu and
      Increased TNF-Related Apoptosis-Induced Ligand Levels.
AB  - Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease.
      Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is
      cytotoxic to a wide variety of transformed cells, but not to most normal cells.
      This study measures serum levels of tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6 and 10 and soluble TRAIL (sTRAIL) in patients with SLE and
      assesses their relation to severity of the disease. The study included 70 SLE
      patients and 20 healthy controls. Patients were diagnosed according to criteria
      proposed by the American Rheumatism Association for classification of SLE and
      disease activity was scored using the British Isles Lupus Assessment Group (BILAG
      2004). All study participants were subjected to estimation of TNF-alpha, IL-6, IL
      10 and sTRAIL using ELISA. Results revealed that mean disease duration was 6.5+/
      1.5 years, mean BILAG score was 18.2+/-12.1, while 15 patients (21.4%) had
      quiescent disease. Blood levels of C3 and C4 and leucocytic count showed
      progressive decrease, while serum C-reactive protein and anti-double strand DNA
      antibodies levels showed marked increase with increased disease activity. Five
      patients (7.1%) were neutropenic. Serum levels of sTRAIL and IL-6 were
      significantly (P>0.05) higher in patients (1113.5+/-294 ng/ml and 60+/-21.5
      ng/ml, respectively) than controls (354.7+/-47.2 ng/ml and 15.6+/-3.3 ng/ml,
      respectively) and in patients had active (1157+/-317 ng/ml and 64.3+/-20.7 ng/ml,
      respectively) versus patients had quiescent disease (965.4+/-115 ng/ml and 45.4+/
      18 ng/ml, respectively). Serum levels of TNF-alpha were significantly (P>0.05)
      higher in patients (2.4+/-0.7 ng/ml) especially those with active (2.8+/-2 ng/ml)
      disease compared to controls (1.45+/-0.9 ng/ml). Patients with quiescent disease
      showed non-significantly higher TNF-alpha level (1.52+/-0.5 ng/ml) as compared to
      control, but significantly lower than patients with active disease. Serum levels
      of IL-10 were significantly lower in total patients (2.4+/-0.7 ng/ml) and
      patients with active disease (2.33+/-0.7) as compared to control (2.61+/-0.6
      ng/ml) with a non-significantly (P>0.05) higher levels in patients with quiescent
      disease (2.61+/-0.6 ng/ml) than patients with active disease. Estimated serum
      sTRAIL, TNF-alpha and IL-6 levels showed positive significant correlation with
      calculated BILAG activity score, while estimated serum IL-10 levels showed
      negative significant correlation with activity score. In conclusion, SLE is
      associated with disturbed levels of serum cytokines and sTRAIL. These
      disturbances may underlie pathogenesis and/or activation of SLE as BILAG-2004
      numeric scoring system significantly correlated with estimated levels of serum
      cytokines and sTRAIL.

PMID- 28502136
TI  - CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis
      Disease Activity.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed
      immune regulation, inducing a progressive cartilage and bone destruction. Despite
      enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results
      are reported concerning T-regs in peripheral blood (PB) of RA patients. To
      determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T
      regs) with RA disease activity. Forty females with RA, classified according to
      the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low
      disease activity; and 20 age and sex matched healthy controls, were enrolled to
      study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had
      lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild
      moderate or low disease activity (P <0.001). The frequencies of the T- regs
      showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+
      CD127low T-regs is significantly lower in highly active RA patients compared to
      patients with lower activity or controls.

PMID- 28502137
TI  - Angiopoietin-2 as A Biomarker For Echocardiographic Abnormalities and Carotid
      Atherosclerosis In Rheumatoid Arthritis Patients.
AB  - Atherosclerosis and cardiovascular diseases (CVD) are increasingly recognised
      complications of rheumatoid arthritis (RA). Angiopoietin 2 (Ang-2) levels have
      been associated with clinically overt CVD in general population; we assessed
      serum Ang-2 levels and its correlation with Echocardiographic abnormalities and
      carotid intima-media thickness in RA patients. 44 RA patients without clinically
      overt CVD and 44 healthy controls were assessed by questionnaire and clinical
      examination. Disease activity score (DAS-28) was calculated. Laboratory
      investigations included measurement of serum Ang-2, Rheumatoid factor (RF), anti
      cyclic citrullinated peptide (Anti-CCP), and C reactive protein (CRP). Doppler
      Echocardiography and Carotid ultrasonography were done to all patients and
      controls. Mean age of RA patients was 44.4+/-9.6 and about (86.4%) 38 were
      females. Mean levels of Ang-2 was higher in RA patients (17.591+/-13.9 ng/ml) as
      compared to controls (7.909 +/-4.10 ng/ml) P<0.001 and was significantly elevated
      in RA patients with left ventricular (LV) diastolic dysfunction (23.53+/-7.75
      ng/ml) than those without dysfunction (14.81+/-15.33ng/ml), P<0.05 and was
      significantly elevated in RA patients with carotid intima-media thickness (cITM)
      >0.6mm (21.12+/-14.79 ng/ml), P<0.005. Serum Ang-2 correlated positively with
      disease duration, DAS-28, LV posterior wall thickness, E wave velocity and cIMT.
      In conclusion, serum Ang-2 level is associated with LV diastolic dysfunction and
      increased carotid intima-media thickness in RA patients and may be useful
      biomarker for subclinical CVD and atherosclerosis in RA patients.

PMID- 28502138
TI  - Presepsin a Diagnostic Marker for Sepsis in Intensive Care Unit Patients.
AB  - The aim of the study was to evaluate the usefulness of presepsin as a diagnostic
      marker of sepsis in intensive care unit (ICU) patients. Presepsin was measured by
      a rapid method based on a chemiluminescent enzyme immunoassay (PATHFAST). The
      clinical usefulness of presepsin to diagnose sepsis and septic shock was studied
      and compared with procalcitonin, C-reactive protein and total leucocytic count.
      This study was conducted on 53 individuals divided into 3 groups. Group I
      included 28 adult ICU patients with at least two diagnostic criteria for systemic
      inflammatory response syndrome (SIRS) as patient group, Group IIa 15 patients
      admitted to ICU for any medical cause but with no evidence of infection were
      enrolled as patient control group and further 10 apparently healthy subjects as
      healthy control group. Patients were further subdivided retrospectively according
      to the final diagnosis into: patients with sepsis 16 (57.1%) and septic shock 12
      (42.9%), from which 17 (59.3%) improved while 11(39.3%) did not survive. The
      presepsin values were significantly higher in patients with sepsis than the
      control groups. The area under ROC curve (AUC) for discriminating sepsis from non
      septic conditions for presepsin was greater than the AUC of PCT, CRP or TLC. This
      suggests that presepsin has high specificity and sensitivity for sepsis
      diagnosis. In conclusion, presepsin can be used as a useful biomarker for the
      diagnosis of sepsis. It is readily available, cost-effective and able to
      distinguish septic patients in a complex population.

PMID- 28502139
TI  - Serum Interleukin-33 in Behcet's Disease: Its Relation to Disease Activity and
      Clinical Manifestations.
AB  - : Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized
      by a course of remissions and exacerbations of unpredictable frequency and
      duration. Pro-inflammatory cytokines seem to be responsible for the enhanced
      inflammatory response in BD. AIM OF THE WORK: This study aimed to investigate
      serum levels of IL-33 in patients with Behcet's disease (BD) and their
      relationship to disease activity and clinical manifestations. Thirty patients
      with BD were enrolled and subjected to assessment of disease activity according
      to Behcet's Disease Current Activity Form (BDCAF) score. Serum IL-33 levels were
      determined using Enzyme-Linked-Immunosorbent Assay (ELISA). Thirty age and sex
      matched rheumatoid arthritis patients and thirty healthy volunteers were included
      in this study as control groups. Serum IL-33 level was 132.5+/-19 pg?ml, 101.2+/
      20.1 pg?ml and 31.5+/-10.5 pg?ml in RA, BD and healthy control groups
      respectively. IL-33 was significantly higher in BD patients (101.2+/-20.1pg/ml)
      as compared to healthy controls (31.5+/-10.5 pg/ml) but lower than rheumatoid
      arthritis patients (132.5+/-19.1 pg/ml). Levels of IL-33 were significantly
      increased in BD patients with skin lesions (Erythema nodosum & Acneiform lesions)
      and ocular lesions (retinal vasculitis) (P<0.05), and a positive correlation was
      found between BDCAF score and IL-33serum levels (r=0.9, P<0.001). In conclusions,
      serum IL-33 level is elevated in active BD patients with skin and ocular
      affection and correlates with disease activity.

PMID- 28502140
TI  - Expression of IL-23 mRNA in Systemic Lupus Erythramtosus Patients: Relation with
      Disease Activity.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue
      disorder characterized by loss of self-tolerance causing immune-mediated tissue
      destruction and various clinical presentations. Cytokine-mediated immunity
      involved in the pathogenesis of SLE. Recently, IL-23 was proposed to play a
      crucial role in mediating tissue inflammation and autoimmunity. The present work
      was aimed to investigate the relation between levels of IL-23 mRNA and disease
      activity in patients with SLE and in those with renal involvement. In this work,
      blood samples from 45 adult patients with SLE and 20 healthy controls were
      collected. Patients were divided into 3 groups. Group I consisted of 16 patients
      with active SLE with nephritis. Group II consisted of 13 patients with active SLE
      without nephritis. Group III consisted of 16 patients with inactive SLE based on
      the SLE disease activity index (SLEDAI). The IL-23 mRNA relative concentration
      was detected by Quantitative Reverse transcriptase- polymerase Chain Reaction (RT
      PCR). IL-23 mRNA expression level in blood was eleven times higher in SLE
      patients without activity while in active SLE patients with and without nephritis
      showed 34 fold and 17 fold higher IL-23 mRNA expression respectively compared to
      healthy control. IL-23 mRNAs levels were significantly higher in patients with
      SLE compared with healthy controls (P < 0.001). Patients with active disease
      showed higher IL-23 mRNAs compared with those with inactive disease as well as
      healthy controls (P < 0.001). IL-23 levels were significantly higher in SLE
      patients with renal involvement compared with those without renal disease (P <
      0.001). It is concluded that IL-23 has a role in the development and pathogenesis
      of SLE & lupus nephritis.

PMID- 28502141
TI  - Effect of Phototherapy on CD4, CD8 and Natural Killer Cells of Full Term Neonates
      with Indirect Hyperbilirubinemia.
AB  - Phototherapy is generally considered a very safe and well-tolerated treatment for
      hyperbilirubinaemia. However, clinical users should be aware of the unwanted
      effects of using phototherapy. Affection of neonatal immune system due to
      phototherapy has been reported. This study aimed to evaluate the effect of
      phototherapy on level of CD4+, CD8+ and natural killer (NK) (CD16+ & CD65+)
      lymphocytes subsets in neonates. The number of these lymphocytes was measured 72
      hrs after phototherapy exposure in 30 full term neonates with indirect
      hyperbilirubinemia and compared to those of 25 healthy controls using flow
      cytometry. Results showed non-significant changes of the tested lymphocyte
      subsets after 72 hrs exposure to phototherapy. In conclusion, phototherapy has no
      significant effect on the level of circulating CD4+, CD8+ and NK lymphocytes.

PMID- 28502142
TI  - APRIL Level as a Marker of Disease Activity in Treated Rheumatoid Arthritis
      Patients: Association with Disease Activity and Anti-CCP Antibody.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease with joint inflammation
      and autoantibody production. Cytokines play an important role in the pathogenesis
      of RA. Among the cytokines that regulate B cell homeostasis is the "A
      Proliferation-Inducing Ligand" (APRIL). To determine the differences in APRIL in
      response to treatment in anti- cyclic citrllinated peptides (anti-CCP) positive
      versus anti-CCP negative patients with established RA. Concentrations of APRIL in
      sera of 10 anti-CCP positive RA patients, 18 anti-CCP negative RA patients, and
      12 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA) at
      treatment initiation and after 6 months of treatment with methotrexate and
      hydroxychloroquine. Correlations between serum anti-CCP, C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score
      (DAS28), and serum level of APRIL were analyzed. Serum APRIL levels were
      increased in rheumatoid arthritis patients in comparison with healthy volunteers.
      APRIL correlated positively with disease activity; swollen joint count, visual
      analog score and simplified disease activity index (all P < 0.05). In addition,
      APRIL was significantly higher in patients with positive anti-CCP. After
      treatment, APRIL levels significantly decreased in the anti-CCP positive RA
      patients than in anti-CCP negative RA patients. In conclusions, serum APRIL may
      be a good predictor marker for joint injury and therapeutic response in patients
      with RA.

PMID- 28502143
TI  - Skin Prick Test Reactivity to Aeroallergens among Egyptian Patients with Isolated
      Allergic Conjunctival Disease.
AB  - Allergic conjunctival disease (ACD) is a type of ocular allergy, which includes
      seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC),
      and vernal keratoconjunctivitis (VKC). Little is known about the pattern of
      sensitization or prevalent aeroallergens among patients with isolated ACD in
      Egypt We aimed to evaluate the prevalence of skin prick test positivity to common
      aeroallergens among Egyptian patients with isolated allergic conjunctival
      disease. The study included 75 patients with isolated ACD recruited from a
      tertiary Egyptian outpatient clinic. Skin prick test (SPT) was performed for all
      patients with common aeroallergens. Total serum immunoglobulin E (IgE) was
      measured by ELISA. A positive SPT reaction was present among 32 patients (42.7%).
      The most prevalent aeroallergens among all patients were mites and pollens (12%
      respectively), followed by grass (8%) and hay dust (6.7%). Eight patients (10.7%)
      had SAC, 19 patients (25.3%) had PAC, and 48 patients (64%) had VKC. Prevalence
      of SPT positivity to indoor allergens was significantly more common among PAC
      (52.6%) than among SAC (25%) and VKC (16.7%), P= 0.011. Outdoor allergen
      sensitization did not differ significantly between the 3 subgroups, P= 0.614.
      Elevated IgE levels were observed among 62.5%, 73.7% and 66.7% of patients with
      SAC, PAC and VKC, respectively, with no statistically significant difference
      between them, P= 0.806. In conclusion aeroallergen sensitization is common among
      Egyptian patients with isolated ACD. Accordingly, SPT should be included in the
      diagnostic workup of these patients.

PMID- 28502144
TI  - Risk Association between TNF-alpha-308 G>A and IL-6-174 G/C Polymorphisms and
      Recurrent Transient Ischemic Attacks.
AB  - Transient ischemic attack (TIA) is a brief cerebral ischemic incident. This study
      assesses the role of TNF-alpha and IL-6 single nucleotide polymorphisms (SNPs) as
      predictors of recurrent TIAs that have high risk of developing stroke. The
      current study enrolled 54 high risk (according to frequency of TIA) TIA (group1),
      52 low risk TIA patients (group2) and 34 controls (group3). Polymerase chain
      reaction (PCR) for DNA amplification was done followed by restriction
      endonuclease analysis to detect SNPs of TNF-alpha-308 G > A and IL-6-174 G/C. TNF
      alpha serum level was analysed by ELISA. Significant increase of TNF-alpha-308 G
      > A allele (group1 compared to group2 and control P=0.0001) and genotype TNF
      alpha-308 AA (P<=0.05) were detected. IL6 allele polymorphism revealed
      insignificant SNPs. The serum TNF-alpha was higher in group1 compared to control
      and group2 and as well in TNF-alpha-308 AA variant in high risk group (P<=0.05).
      It is concluded that TNF-alpha-308 G > A SNP might have a role in predicting
      recurrent TIA with impact on preventive measures of stroke development.

PMID- 28502145
TI  - Study of Interleukin 28B rs12979860 and rs8099917 Polymorphisms and T-helper 1
      Response in Hepatitis C Virus Patients.
AB  - HCV infection is a serious public health problem and a leading cause of chronic
      liver disease. It affects nearly 3% of the world's population with an associated
      high mortality. Egypt has the highest prevalence of HCV infection in the world
      (estimated at >10%). Peg-IFN-alpha and RBV are the most widely used therapy for
      HCV. Unfortunately, the rate of SVR is around 50%. In addition, it is expensive
      and associated with considerable adverse effects. Thus selection of patients with
      the highest probability of response is essential for clinical practice. It is
      suggested that some SNPs near IL- 28B gene could be important genetic predictors
      of treatment response among HCV. Our study aimed to study two different
      Interleukin 28B polymorphisms (rs12979860 and rs8099917) and T-helper 1 response
      in HCV infected patients. The current study was conducted on 60 chronic HCV
      infected patients and 20 healthy volunteers. Grouping of patients was done
      according to response to treatment into naive, responder and non-responder HCV
      patients. Assessment of liver functions' tests, measuring HCV RNA levels using
      real time PCR, measurement of interferon-gamma levels using ELISA and genotyping
      of IL-28 rs2979860 and rs8099917 SNPs using 5' nuclease assay were done.
      Concerning IL-28B rs12979860; TT genotype was highly expressed in non-responder
      HCV patients but statistically insignificant. While for IL-28B rs8099917, there
      was lack of association between its different genotypes and SVR. IFN-? level was
      significantly increased among responder HCV patients carrying IL28B rs12979860 TT
      genotype and/or IL28B rs8099917 GG allele. There was statistically significant
      positive correlation between L28B rs8099917 GG genotype and HCV-RNA. In
      conclusion, IL-28B rs12979860 SNP could be used as an independent predictor for
      treatment response among HCV patients.

PMID- 28502146
TI  - Brewer's Yeast Supplementation Enhances Immune Response of Aged Mice.
AB  - A large amount of evidence indicates that aging is associated with immune system
      dysfunction. Brewer's yeast, one of the most notable species of yeast in health
      and wellness, has been shown to stimulate the immune system and improve human
      life span. In the present study, brewer's yeast (5, 25 or 125 MUg/mouse) was
      orally supplemented to aged mice each other day for 4 weeks. Total number of
      leukocytes from peripheral blood (PBl), thymus (Thy), spleen (Sp), and peritoneal
      exudate cells (PEC) were counted. Carbon clearance, plaque-forming cell and
      rosette-forming cell assays were used to measure macrophage, B cell and T cell
      responses. In vitro proliferation of splenocytes and histological architecture of
      thymus from aged mice were tested. Yeast treated mice showed a significant
      increase in the total number of PBl leukocytes, total cellularity of both Thy and
      Sp, as well as a significant increase in total and differential numbers of PEC. A
      gradual increase in macrophages' phagocytic activity of PEC and a significant
      increase in both plaque-forming cell and rosette-forming cell responses were
      observed. In vitro results showed that incubation of splenocytes with brewer's
      yeast (0.5, 2.5 or 12.5MUg/well) in the presence of concanavalin-A mitogen
      elicited a gradual increase in the proliferation of splenocytes. Histological
      examination of thymuses from yeast-treated aged mice revealed that the cortex was
      preferentially enlarged and repopulated with immature thymocytes. These results
      indicate that brewer's yeast supplementation to aged mice improves several
      baseline immune responses, and provides a valuable tool to identify nutritional
      strategies that could mitigate immunosenescence.

PMID- 28502147
TI  - Surface Expression and Genetic Variants of Toll-like Receptor 2 in Pulmonary
      Tuberculosis Patients.
AB  - Innate immunity plays an important role in the host defense against Mycobacterium
      tuberculosis (M. tuberculosis). Toll-like receptor-2 (TLR2) is the main receptor
      and one of central components in initiation of innate immunity against M.
      tuberculosis. The study aimed to evaluate TLR2 surface expression on peripheral
      blood monocytes and study its association with variants in TLR2 597T/C single
      nucleotide polymorphisms (SNPs) in patients with pulmonary tuberculosis. Fifty
      pulmonary tuberculosis patients and 50 healthy controls were investigated for
      TLR2 expression on CD14+ monocytes by flow cytometry and TLR2 597T/C genotyping
      by Tetra primer amplification refractory mutation system-polymerase chain
      reaction (T-ARMS-PCR). A significant increase (P < 0.001) in TLR 2 expression was
      detected in tuberculosis patients compared to controls. TLR2 597 TC and CC
      genotypes were higher in pulmonary tuberculosis patients (OR =2.79, 95% CI =1.02
      7.95 and OR =4.26, 95% CI =0.40-214.00) respectively. Genotype TT was associated
      with reduced risk of being a case of pulmonary tuberculosis. There was no
      association of TLR2 surface expression on monocytes in pulmonary tuberculosis
      patients with different TLR2 597T/C genotypes. It is concluded that elevated
      expression of TLR2 on CD14+ monocytes in pulmonary tuberculosis patients confirms
      the role of TLR2 in host defense against M. tuberculosis. 597T/C polymorphism of
      TLR 2 gene may be a risk factor for susceptibility to pulmonary tuberculosis in a
      sample Egyptian population.

PMID- 28502148
TI  - Sperm DNA Fragmentation Index and Intracytoplasmic Sperm Injection Outcome in
      Egyptian Couples.
AB  - Sperm of infertile men mostly contain more DNA damage than their fertile
      counterparts. Sperm DNA damage might have a negative effect on the fertility
      potential of such patients. This study measures the percentage of spermatozoa
      with nuclear DNA fragmentation in semen samples used for intacytoplasmic sperm
      injection (ICSI), before and after sperm processing and investigates the
      association between sperm DNA fragmentation index (DFI) and ICSI outcome (embryo
      grade and clinical pregnancy). Sperm DFI was measured, by TUNEL, in fresh semen
      samples obtained from thirty male partners of infertile couples, seeking ICSI
      treatment. The mean sperm DFI before and after processing was 4.5% and 8.83%
      respectively. Sperm DFI increased significantly after processing (P < 0.001)
      regardless the type of processing used (P= 0.877). The correlation between sperm
      DFI, before and after semen processing, and clinical pregnancy was statistically
      insignificant (P=0.689 and P=0.631 respectively). DFI of sperm after semen
      processing showed a significant negative correlation with embryo grading at day 3
      (r = - 0.232, P = 0.002). In conclusion, sperm DFI increases significantly after
      processing and correlates negatively with embryo grade.

PMID- 28502149
TI  - Serum Level of Interleukin-37 and Expression of Its mRNA in Ankylosing
      Spondylitis Patients: Possible Role in Osteoporosis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial
      skeleton.Interleukin-37 (IL-37) is a member of IL-1 family cytokines, that
      downregulate expression of pro-inflammatory cytokines in chronic inflammatory
      diseases. The aim of the work is to investigate role of IL-37 in AS disease
      activity and osteoporosis. Twenty-five patients with AS and 25 controls were
      enrolled into this study. They were subjected to full clinical examination
      including assessment of disease activity according to the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI). Serum IL-37 levels and IL-37 mRNA
      relative concentration were measured by enzyme-linked immunosorbent assay (ELISA)
      and quantitative reverse transcriptase- polymerase chain reaction (RT-PCR)
      respectively. Bone mineral density (BMD) was determined using dual energy X-ray
      absorptiometry (DEXA). Spine radiographs were scored using the modified Stoke
      Ankylosing Spondylitis Spine Score (mSASSS). Mean serum IL-37 level was
      significantly higher in AS patients compared with the controls (P < 0.001) and
      significantly elevated in AS patients with osteoporosis (P < 0.05). IL-37 mRNA
      gene expression showed a significant increase expression in active AS patient (25
      folds) as well as in inactive patient (12 folds) as compared to controls. In
      conclusion, serum IL-37 and its mRNA expression is increased in AS patients with
      special consideration in patient with Osteoporosis and correlates with disease
      activity and BMD which indicate that IL-37 may provide a novel research target
      for pathogenesis and therapy of AS..

PMID- 28502150
TI  - Suspected Allergic Bronchopulmonary Aspergillosis Cases in Adult Bronchial Asthma
      Patients Attending a Tertiary Care Clinic.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to
      Aspergillus species (generally Aspergillus fumigatus) that occurs almost
      exclusively in patients with asthma or, less commonly, cystic fibrosis. Immune
      responses to Aspergillus antigens cause airway obstruction and, if untreated,
      bronchiectasis and pulmonary fibrosis. Our objective was to define the clinical
      characteristics, laboratory and radiological findings of suspected ABPA cases
      among a cohort of Egyptian patients with bronchial asthma. 52 moderate and severe
      asthma patients were recruited from the Allergy and Immunology clinic at Ain
      Shams University hospitals. Patients were subjected to history taking for asthma
      symptoms, skin test with Aspergillus fumigatus antigen, total IgE level,
      peripheral blood eosinophilia, chest x-ray and high resolution CT chest. 27
      patients had positive skin prick and /or intradermal test to Aspergillus
      fumigatus antigen, and 11 (21.2%) of them fulfilled 4 of the criteria for ABPA
      diagnosis. Patients with suspected ABPA had significantly higher serum total IgE
      levels (median (IQR) = 625 IU/ml (514.9-762) with P-value <0.0001). Our study
      suggests a high frequency of suspected ABPA cases for further confirmation by
      appropriate diagnostic tests; there is a need for better recognition of ABPA as
      it is yet under recognized in Egypt Clinicians ought to have a high index of
      suspicion for ABPA while managing any patient with bronchial asthma to detect
      ABPA prior to development of irreversible complications.

PMID- 28502151
TI  - Percentage of CD3-CD56+dim and of CD3-CD56+dimCD69+ Natural Killer Cells in the
      Peripheral Blood of Women with In Vitro Fertilization (IVF) Failure.
AB  - CD56dim cells, potent mediators of natural cytotoxicity, have direct contact with
      chorionic villi at the intervillous space. The manner the developing fetus evades
      NK cytotoxicity from these cells may determine the pregnancy outcome. CD69 is one
      of the earliest cell surface activation markers expressed by NK cells. In vitro
      models demonstrated that activated CD69+ NK cells are capable of lysing
      trophoblasts. This study aimed to investigate the relation between the percentage
      of these NK cells in peripheral blood and infertility. The study included two
      groups, each of 30 women, one with previous implantation failure and a fertile
      matching control group. CD3-CD56+dim and CD3-CD56+dimCD69+ NK were analyzed by
      flow cytometry. A higher percentage of CD3-CD56+dim and CD3-CD56+dimCD69+ in the
      study group than the control group was observed (P=0.0001 and P=0.003,
      respectively). Fair predictive values were evidenced by ROC curve analysis. We
      conclude that increase in CD56+dim NK and CD56+dim CD69+ NK cell percentages may
      be related to infertility problems.

PMID- 28502152
TI  - Assessment of Nasal Immunoglobulin E Level in Atopic and Non-atopic Rhinitis
      Patients: A Tool for Diagnosis of Local Allergic Rhinitis.
AB  - Many cases of AR can be miss-diagnosed due to deficiency in the conventional
      laboratory tools. Detection of local Ig E immune response and allergy associated
      genes may aid in diagnosis of these cases. The local immune response and the
      allergy associated genes of these suspected cases must be evaluated as they may
      help in their characterization. This study was conducted on 129 patients with
      chronic rhinitis to determine the frequency of LAR, and analyze the association
      of IgE receptor (FcepsilonR1beta) gene polymorphism with LAR. All participants
      were subjected to clinical questionnaire, skin prick test, specific IgE
      measurement in serum and nasal secretions and analysis of FcepsilonR1beta gene
      polymorphism. LAR constituted 24.8 % of total rhinitis cases and 44.4% of non
      allergic cases. Cockroach was the main sensitizing agent in local allergic
      rhinitis in comparison with allergic cases (OR =0.11; 95% CI= 0.04-0.34;
      P<0.001). In LAR, nasal specific Ig E was significantly lower than that in AR
      patients (P < 0.001). FcepsilonR1beta genotype TT was more frequently expressed
      in LAR and AR than non-allergic rhinitis (NAR) (P< 0.001). It is concluded that
      LAR is an emerging allergic condition that could be diagnosed by nasal specific
      IgE, and that FcepsilonR1beta polymorphism is one of the genetic factors
      associated with AR and LAR.

PMID- 28502153
TI  - Immunotherapeutic Approach to Breast Cancer: The Anti-Tumor Effect of Anti-IL-6
      Monoclonal Antibodies in Malignant Mammary Tumor Implanted-Mice.
AB  - It has been established that suppression of apoptosis during carcinogenesis is
      the main cause of development and progression of breast cancer. Breast cancer
      patients have higher circulating levels of IL-6 protecting cancer cells from
      apoptosis and positively correlated with poor prognosis of the disease. The
      current work is carried out to fulfill one of our in vivo preclinical studies'
      for approaching a novel breast cancer immunotherapy through induction of tumor
      cell apoptosis. The study aims at investigating the potential of anti-IL-6
      monoclonal antibodies (mAbs) to suppress IL-6 anti-apoptotic activities in tumor
      microenvironment of malignant mammary tumor implanted-mice. To achieve this goal,
      4 groups of mice were used, group I: served as control, group II: mice implanted
      with Ehrlich ascites carcinoma cell lines (EAC), through intramuscular injection
      till tumor inoculation, group III: injected intratumorally with10 ul saline for 3
      successive days, and group IV: mice were injected intratumorally one day after
      tumor inoculation with a dose of 1.5 mg / kg of recombinent anti-IL-6 monoclonal
      antibodies in10 ul saline for 3 successive days. Apoptosis was evaluated in tumor
      samples from anti-IL-6 treated tumor implanted mice and compared with controls.
      Levels of apoptosis in tumor tissue samples of tumor implanted mice treated with
      anti-IL-6 were significantly (P=0.009) higher than untreated ones. In conclusion,
      anti-IL-6 monoclonal antibodies have the potential to suppress the anti-apoptotic
      effect of interleukin-6 (IL-6) within the tumor microenvironment of tumor
      implanted in mice.

PMID- 28502154
TI  - Helicobacter pylori Infection as a Risk Factor in Patients Suffering from Food
      Allergy and Urticaria.
AB  - H. pylori infection is common worldwide. Many intestinal and extra intestinal
      manifestations have been associated with H. pylori infection. H. pylori destruct
      the gastric lining which allows food allergens to get access to blood,
      predisposing to Food allergy. Previous works considered chronic urticaria as a
      known symptom for food allergy and a skin manifestation for H. pylori infection.
      The aim of this work is to provide evidence based recommendation for detecting H.
      pylori antigen in stool in patient suffering from both food allergy and chronic
      urticaria. We determined the frequency of H. pylori Ag in stool in a group of
      patients complaining from both disorders and compared it with a group of
      apparently healthy control subjects with no history of either urticaria or food
      allergy. Our results showed that the frequency of H. pylori Ag in stool in
      control group was 62.5 %, while, it was 97 % in patient group. When we calculated
      the risk of H. pylori infection in predisposing to both disorders, odds ratio was
      18.6. According to these results we concluded that H. pylori is a risk factor for
      developing chronic urticaria and food allergy and we recommend testing for H.
      pylori Ag in stool in patients complaining from these disorders.

PMID- 28502155
TI  - Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden
      Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.
AB  - Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid
      hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of
      population worldwide. A key feature of autoimmune thyroiditis is the presence of
      anti TPO antibodies, and some mutation of the TPO gene. Association between
      autoimmune thyroiditis and other autoimmune disorders has been reported but
      little is known about association with allergic diseases. In this study, we aimed
      to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and
      examine possible relationship between anti-TPO levels and polymorphism at the TPO
      gene A2173/C exon 12 and different types of allergens. The study included 50
      adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50
      controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4)
      and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti
      TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was
      analyzed using restriction fragment length polymorphism (RFLP). Skin prick test
      was done to assess allergic response in patients. Serum levels of T3, T4 and TSH
      did not show any statistical significant difference between patients and groups.
      However, mean serum anti-TPO level was statistically higher in patients than
      controls, and correlated positively with body mass index, age, diastolic blood
      pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in
      allergic patients than in control group. 2173A>C Genotyping revealed that the
      frequency of C allele is increased in the patient group. C allele represents a
      risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value <0.05.
      It is concluded that TPO 2173A>C polymorphism may be considered as a risk factor
      for developing autoimmune thyroiditis in patients with allergic rhinitis and
      asthma and that these patients should regularly be checked for hidden
      thyroiditis.

PMID- 28502156
TI  - HCV Infection Amplified Th2 Bias and Th17 Responses In Schistosoma-Infected
      Patients.
AB  - Schistosomiasis and HCV are the most prevalent infections in Egypt Schistosoma
      infection is associated with bias towards Th2 responses. Plasma from 17
      (Schistosoma-infected), 39 (Schistosoma/HCV co-infected) and 23 controls were
      collected. Cytokine multiplex array was used to measure 6 plasma cytokine levels
      representing the surrogate markers of three T helper lymphocytes subpopulations;
      IL-12 (Th1), IL-4 and IL-10 (Th2), IL-17, IL-22 and IL-23 (Th17). There was a
      significant increase in plasma levels of IL-17 and IL-23 in co-infected patients
      compared to Schistosoma-infected patients. As well, there was a significant
      increase in the Th2 regulatory cytokines IL-10 and IL-4 in co-infected group
      compared to Schistosoma-infected patients. However, no significant changes were
      observed in the Th1 cytokine (IL-12) among the groups. In conclusion, presence of
      HCV infection shifted the response towards Th2/Th17 pathway which may play a role
      in the progressive pathogenesis of HCV in Schistosoma-co-infected patients.

PMID- 28502157
TI  - Study of Serum Immunoglobulin Levels and T lymphocyte Subsets in Children with
      Beta Thalassemia with Iron Overload in Egypt.
AB  - Beta thalassemia is an inherited hemoglobin disorder resulting in chronic
      hemolytic anemia that requires lifelong transfusion therapy. Repeated blood
      transfusions and RBCs hemolysis are the main causes of iron overload, which in
      addition to immune abnormalities, are common predisposing factors to infection in
      patients with thalassemia. The aim was to study serum immunoglobulin levels and T
      lymphocyte subsets in children with beta- thalassemia in relation to iron
      overload. This study was conducted on 40 children with beta thalassemia major
      including 24 males and 16 females with mean age of 9.22 +/- 3.9 and 20 healthy
      children of matched age and sex as a control. All children were subjected to
      assessment of infection episodes, complete blood picture, Hb electrophoresis,
      serum iron status, T cell subsets including CD3, CD4 and CD8 using Becton
      Dickinson FAC Scan flow cytometer and serum immunoglobulin levels including IgM,
      IgA and IgG by a commercial nephelometry assay using a BN-II device. Serum
      ferritin and iron were significantly higher but total iron binding capacity was
      significantly lower in patients than controls (Mean serum ferritin was 3418.23+/
      2950.7 in the studied patients versus 39.48+/-2.48 in the control group with p
      value of 0.00, mean serum iron was 222+/-56.61 in the studied patients versus
      90+/-31.87 in the control group with P value of 0.00 and mean serum total iron
      binding capacity was 198.38+/-19.9in the studied patients versus 315.7+/-24.85 in
      the control group with P value of 0.00). CD3 and CD4 were significantly lower but
      CD8 was significantly higher in patients than controls. The count (mean +/- SD
      cells/ mm2) for CD3+, CD4+ and CD8+ T cells in patients was 1733.25 +/- 381.87,
      889.67 +/- 282.86 and 779.72 +/- 390.63 respectively as compared to 1887 +/-
      390.56, 1003 +/- 250.96 and 663 +/- 116.71 in the control group respectively (P
      values 0.00, 0.048 and, 0.02 respectively). The mean +/- SD (mg/dl) of serum
      immunoglobulin's G, M and A showed significant variation between patients and
      controls including significantly lower IgM and significantly higher IgG, and IgA
      in patients than controls with P values of 0.014, 0.049 and 0.020 for G, M, and A
      respectively).There were significant negative correlations between CD3, CD4, IgM
      and ferritin and significant positive correlations between CD8, IgG, IgA and
      ferritin. In conclusion; Iron overload affects humeral and cell mediated immunity
      in thalassemic patients therefore regular follow up for iron overload is
      recommended.

PMID- 28502158
TI  - Significance of Anti-C1q Antibodies in Patients with Systemic Lupus Erythematosus
      as A Marker of Disease Activity and Lupus Nephritis.
AB  - Anti-C1q autoantibodies have been proposed as a useful marker in SLE. This study
      aimed at measuring serum levels of anti-C1q antibodies in patients with SLE and
      investigates correlations of this level with the histopathological classes of
      renal biopsies and disease activity. The anti-C1q antibody level was measured in
      30 females SLE patients and 20 controls. The activity of SLE disease was
      calculated according to the SLE disease activity index. A renal biopsy from
      patients with clinical manifestations of renal disease was obtained. There was a
      significant increase in the level of anti-C1q antibodies in SLE patients than
      controls and in patients with active LN than inactive LN (P<0.05). There were
      significant positive correlations between anti-C1q antibody level and SLEDAI &
      rSLEDAI scores and activity index score of renal biopsies. Anti-C1q antibodies
      showed higher diagnostic sensitivity and specificity than anti-dsDNA antibodies.
      In conclusion, anti-C1q antibodies are useful and sensitive non-invasive
      biomarker with high specificity in combination with anti-dsDNA antibodies for the
      diagnosis of renal disease activity.

PMID- 28502160
TI  - Sarcoidosis with splenic involvement diagnosed via endoscopic ultrasound-guided
      fine-needle biopsy.

PMID- 28502159
TI  - LPL gene Pvu II polymorphism and hypertriglyceridemia: a meta-analysis involving
      1,640 subjects.
AB  - BACKGROUND/AIMS: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has
      been associated with an increased risk of hypertriglyceridemia (HT), there is no
      clear consensus within the scientific community. METHODS: A meta-analysis of
      1,640 subjects from six individual studies was conducted to better elucidate the
      potential relationship between the LPL gene Pvu II polymorphism and HT within the
      Chinese population. Pooled odds ratios (ORs) and their corresponding 95%
      confidence intervals (CIs) were evaluated by using fixed effect models. RESULTS:
      Our analysis indicated a significant association between LPL gene Pvu II
      polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95%
      CI, 1.320 to 1.830; p = 1.158 * 10-7), recessive (OR, 0.540; 95% CI, 0.390 to
      0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 * 10
      8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 * 10-5),
      heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 * 10-6), and additive
      genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 * 10-7).
      CONCLUSIONS: Because LPL gene Pvu II restriction fragment length polymorphism
      polymorphism was associated with an elevated risk of HT, the P+ allele carriers
      of the LPL gene might be predisposed to HT.

PMID- 28502161
TI  - Formation and Inhibition of Metallic Lithium Microstructures in Lithium Batteries
      Driven by Chemical Crossover.
AB  - The formation of metallic lithium microstructures in the form of dendrites or
      mosses at the surface of anode electrodes (e.g., lithium metal, graphite, and
      silicon) leads to rapid capacity fade and poses grave safety risks in
      rechargeable lithium batteries. We present here a direct, relative quantitative
      analysis of lithium deposition on graphite anodes in pouch cells under normal
      operating conditions, paired with a model cathode material, the layered nickel
      rich oxide LiNi0.61Co0.12Mn0.27O2, over the course of 3000 charge-discharge
      cycles. Secondary-ion mass spectrometry chemically dissects the solid-electrolyte
      interphase (SEI) on extensively cycled graphite with virtually atomic depth
      resolution and reveals substantial growth of Li-metal deposits. With the absence
      of apparent kinetic (e.g., fast charging) or stoichiometric restraints (e.g.,
      overcharge) during cycling, we show lithium deposition on graphite is triggered
      by certain transition-metal ions (manganese in particular) dissolved from the
      cathode in a disrupted SEI. This insidious effect is found to initiate at a very
      early stage of cell operation (<200 cycles) and can be effectively inhibited by
      substituting a small amount of aluminum (~1 mol %) in the cathode, resulting in
      much reduced transition-metal dissolution and drastically improved cyclability.
      Our results may also be applicable to studying the unstable electrodeposition of
      lithium on other substrates, including Li metal.

PMID- 28502162
TI  - Identification of Major Sources of Atmospheric NH3 in an Urban Environment in
      Northern China During Wintertime.
AB  - To assess the relative contributions of traffic emission and other potential
      sources to high levels of atmospheric ammonia (NH3) in urban areas in the
      wintertime, atmospheric NH3 and related pollutants were measured at an urban
      site, ~300 m from a major traffic road, in northern China in November and
      December 2015. Hourly average NH3 varied from 0.3 to 10.8 ppb with an average of
      2.4 ppb during the campaign. Contrary to the common perspective in literature,
      traffic emission was demonstrated to be a negligible contributor to atmospheric
      NH3. Atmospheric NH3 correlated well with ambient water vapor during many time
      periods lasting from tens of hours to several days, implying NH3 released from
      water evaporation is an important source. Emissions from local green space inside
      the urban areas were identified to significantly contribute to the observed
      atmospheric NH3 during ~60% of the sampling times. Evaporation of predeposited
      NHx through wet precipitation combined with emissions from local green space
      likely caused the spikes of atmospheric NH3 mostly occurring 1-4 h after morning
      rush hours or after and during slight shower events. There are still ~30% of the
      data samples with appreciable NH3 level for which major contributors are yet to
      be identified.

PMID- 28502163
TI  - Constraining the Spatial Extent of Marine Oil Snow Sedimentation and Flocculent
      Accumulation Following the Deepwater Horizon Event Using an Excess 210Pb Flux
      Approach.
AB  - Following the Deepwater Horizon (DWH) event in 2010, there were several lines of
      evidence indicating the presence of marine oil snow sedimentation and flocculent
      accumulation (MOSSFA). A significant amount of marine oil snow formed in the
      water column of the northern Gulf of Mexico (nGoM), settled rapidly, and
      ultimately accumulated in the sediments of the nGoM. This study utilized a
      commonly used radioisotope tracer (excess 210Pb, 210Pbxs) from 32 sediment cores
      collected from 2010 to 2013 to characterize the spatial extent of MOSSFA on the
      seafloor. Relative to pre-DWH conditions, an increase in 210Pbxs flux occurred in
      two distinct regions: (1) in the western portion of the study area on an east
      northeast to west-southwest axis, stretching 230 km southwest and 140 km
      northeast of the DWH wellhead, and (2) in the eastern portion of the study area
      on a 70 km northeast to southwest axis near the DeSoto Canyon. The total
      sedimentary spatial extent of MOSSFA, as calculated by increased 210Pbxs flux
      after 2010, ranged from 12 805 to 35 425 km2. 210Pbxs flux provides a valuable
      tool for documenting the spatial extent of MOSSFA following DWH and will continue
      to aid in the determination of advective transport and ultimate depocenters of
      MOSSFA material.

PMID- 28502165
TI  - Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by
      Suppression of AP-1 and NF-kappaB via p38 MAPKs/JNK Signaling Pathways in
      Respiratory Syncytial Virus-Infected A549 Cells.
AB  - Airway epithelial cells are often infected by respiratory syncytial virus (RSV),
      one of the most common causes of asthma, bronchiolitis, chronic obstructive
      pulmonary disease, and pneumonia. During the infection process, excessive mucins
      instigate airway inflammation. However, the mechanism underlying RSV-induced
      airway hyper-responsiveness and inflammation is poorly understood. Furthermore,
      no reliable vaccines or drugs for antiviral therapy are available. In this study,
      the effect of the natural compound grape seed proanthocyanidin (GSP) on RSV
      infected human airway epithelial cells A549 was evaluated. After pretreatment of
      the cells with or without exposure to RSV with 5-10 MUg GSP/mL, the expression of
      various mucins (MUC1, MUC2, MUC5AC, MUC5B, and MUC8) was evaluated by real-time
      polymerase chain reaction, enzyme-linked immunosorbent assay, and Western
      blotting, as well as confocal microscopy. We found that GSP significantly
      decreased RSV-induced mucin synthesis at the mRNA and protein levels. In
      addition, GSP suppressed the RSV-induced signaling pathways, including
      extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together
      with nuclear factor kappa B (NF-kappaB) and activating protein-1 family members
      (c-Jun and c-Fos). Concomitantly, GSP inhibited the replication of RSV within
      A549 cells. Taken together, all our results suggest that GSP could be a potent
      therapeutic agent to suppress excessive mucus production and viral replication in
      RSV-induced airway inflammatory disorders.

PMID- 28502164
TI  - Direct 11CN-Labeling of Unprotected Peptides via Palladium-Mediated Sequential
      Cross-Coupling Reactions.
AB  - A practical procedure for 11CN-labeling of unprotected peptides has been
      developed. The method was shown to be highly chemoselective for cysteine over
      other potentially nucleophilic residues, and the radiolabeled products were
      synthesized and purified in less than 15 min. Appropriate for biomedical
      applications, the method could be used on an extremely small scale (20 nmol) with
      a high radiochemical yield. The success of the protocol stems from the use of a
      Pd-reagent based on a dihaloarene, which enables direct "nucleophile-nucleophile"
      coupling of the peptide and [11C]cyanide by temporal separation of nucleophile
      addition.

PMID- 28502166
TI  - Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass
      Spectrometry to Enable Chemical Composition-Based Read-Across.
AB  - Substances of Unknown or Variable composition, Complex reaction products, and
      Biological materials (UVCBs), including many refined petroleum products, present
      a major challenge in regulatory submissions under the EU Registration,
      Evaluation, Authorisation and Restriction of Chemicals (REACH) and US High
      Production Volume regulatory regimes. The inherent complexity of these
      substances, as well as variability in composition obfuscates detailed chemical
      characterization of each individual substance and their grouping for human and
      environmental health evaluation through read-across. In this study, we applied
      ion mobility mass spectrometry in conjunction with cheminformatics-based data
      integration and visualization to derive substance-specific signatures based on
      the distribution and abundance of various heteroatom classes. We used petroleum
      substances from four petroleum substance manufacturing streams and evaluated
      their chemical composition similarity based on high-dimensional substance
      specific quantitative parameters including m/z distribution, drift time, carbon
      number range, and associated double bond equivalents and hydrogen-to-carbon
      ratios. Data integration and visualization revealed group-specific similarities
      for petroleum substances. Observed differences within a product group were
      indicative of batch- or manufacturer-dependent variation. We demonstrate how high
      resolution analytical chemistry approaches can be used effectively to support
      categorization of UVCBs based on their heteroatom composition and how such data
      can be used in regulatory decision-making.

PMID- 28502167
TI  - Transient Porosity in Densely Packed Crystalline Carbazole-(p-Diethynylphenylene)
      Carbazole Rotors: CO2 and Acetone Sorption Properties.
AB  - We report for the first time the high sorption properties of a molecular rotor
      with no permanent voids or channels in its crystal structure. Such crystalline
      phase originates from THF, DCM, or the irreversible desolvation of entrapped
      benzene molecules. From these, the benzene in its solvate form acts as rotation
      stopper, as supported by dynamic characterization using solid-state 2H NMR
      experiments. In the solvent-free form, the diffusion of small quantities of
      iodine vapors caused a significant change in the intramolecular rotation,
      increasing the known activation energy to rotation from 8.5 to 10.6 kcal mol-1.
      Notably, those results paved the way for the discovery of the high CO2 uptake
      (201.6 cm3 g-1 at 196 K, under 1 atm) and acetone (5 wt %), a sorption property
      that was attributed to both, the restriction of the molecular rotation at low
      temperatures and the flexibility of the molecular axle made of conjugated p
      (ethynylphenylene), surrounded by carbazole.

PMID- 28502168
TI  - Age Dating of Individual Micrometer-Sized Uranium Particles by Secondary Ion Mass
      Spectrometry: An Additional Fingerprint for Nuclear Safeguards Purposes.
AB  - A direct and simultaneous analysis of the age and isotopic composition of nuclear
      material at the particle scale is described in this study. By comparison with
      other conventional techniques such as inductively-coupled plasma mass
      spectrometry or thermal-ionization mass spectrometry, secondary ion mass
      spectrometry enables one to determine the ages of individual particles in a
      mixture of nuclear materials. Having access to the purification date can give
      precious information on the history of a nuclear facility or nuclear material for
      safeguarding purposes. The high sensitivity of this technique combined with its
      imaging capabilities enables one to detect and to sort out all particles
      according to their isotopic composition in one analysis. The succession of two
      microbeam analyses on an individual particle allows the determination of the
      precise 235U abundance and the model age. The methodology was successfully
      applied to a mixture of uranium particles coming from certified reference
      material with a 235U abundance ranging from 10% to 97%: the accuracy on the 235U
      abundance is greater than 0.5% and the accuracies on the 235U abundance and the
      model age are better than 0.5% and 3%, respectively.

PMID- 28502169
TI  - Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an
      Overlooked Risk in Plants?
AB  - Agricultural use of treated wastewater, biosolids, and animal wastes introduces a
      multitude of contaminants of emerging concerns (CECs) into the soil-plant system.
      The potential for food crops to accumulate CECs depends largely on their
      metabolism in plants, which at present is poorly understood. Here, we evaluated
      the metabolism of naproxen and ibuprofen, two of the most-used human drugs from
      the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The
      complementary use of high-resolution mass spectrometry and 14C labeling allowed
      the characterization of both free and conjugated metabolites, as well as
      nonextractable residues. Naproxen and ibuprofen, in their parent form, were
      conjugated quickly and directly with glutamic acid and glutamine, and further
      with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of
      naproxen accounted for >90% of the extractable chemical mass, while the intact
      parent itself was negligible. The structures of glutamate and glutamine
      conjugates were confirmed using synthesized standards and further verified in
      whole plants. Amino acid conjugates may easily deconjugate, releasing the parent
      molecule. This finding highlights the possibility that the bioactivity of such
      CECs may be effectively preserved through direct conjugation, a previously
      overlooked risk. Many other CECs are also carboxylic acids, such as the profens.
      Therefore, direct conjugation may be a common route for plant metabolism of these
      CECs, making it imperative to consider conjugates when assessing their risks.

PMID- 28502171
TI  - Complexation of a Globular Protein, beta-Lactoglobulin, with an Anionic
      Surfactant in Aqueous Solution.
AB  - The complexation of a globular protein, beta-lactoglobulin (BLG), and an anionic
      surfactant sodium dodecyl sulfate (SDS) in aqueous media was investigated using
      capillary zone electrophoresis, electrophoretic, static, and dynamic light
      scattering, and small-angle X-ray scattering in a considerably high protein
      concentration range (0.27 mM < CP < 3 mM). On increasing the molar concentration
      CR of the surfactant, cooperative binding of SDS to BLG starts at CR/CP ~ 1; the
      BLG-SDS complex consists mainly of the BLG dimer and approximately 20 SDS
      molecules, where BLG takes a compact conformation similar to that of the native
      BLG up to CR/CP ~ 20. At CR/CP higher than 30, the BLG dimer in the BLG-SDS
      complex dissociates into a unimer, but the dissociated BLG unimer still takes a
      compact conformation at least at 30 < CR/CP < 65.

PMID- 28502170
TI  - A Low-Energy Ion Scattering Approach for Studying Au Nanoclusters Grown on an H2O
      Buffer Layer.
AB  - A novel form of alkali low-energy ion scattering is used to probe the deposition
      of nanoclusters onto a solid surface via buffer layer assisted growth (BLAG) in
      ultrahigh vacuum. A thin amorphous solid water (ASW) buffer layer is grown on a
      TiO2(110) single crystal cooled to 100 K. Au atoms deposited onto this layer
      arrange themselves into nanoclusters. The sample is then annealed to 320 K to
      desorb the ASW and enable the clusters to soft-land onto the substrate. Time-of
      flight low-energy ion scattering, using Li+, Na+, and K+ projectiles, probes the
      materials during each step of the BLAG process to measure the surface composition
      and reveal the details of how the clusters form. The neutralization probability
      of Na+ ions singly scattered from the Au nanoclusters indicates that they
      increase in size after annealing and that the magnitude of the increase is a
      function of the buffer layer thickness. The adsorption of a thin, incomplete
      water layer prior to Au deposition forms nanoclusters that are possibly even
      smaller than those produced by direct deposition onto the clean substrate.

PMID- 28502172
TI  - Direct Dopant Patterning by a Remote Monolayer Doping Enabled by a Monolayer
      Fragmentation Study.
AB  - The development of new doping methods extending beyond the traditional and well
      established techniques is desired to match the rapid advances made in
      semiconductor (SC)-processing methods and nanostructure synthesis in numerous
      emerging applications, including the doping of 3D architectures. To address this,
      monolayer doping (MLD) and monolayer contact doping methods have been introduced
      recently. The MLD methods enable separation of the doping process of
      nanostructures from the synthesis step; hence, it is termed ex situ doping. Here,
      we present a new ex situ MLD method termed remote MLD (R-MLD). The noncontact
      doping method is based on the thermal fragmentation of dopant-containing
      monolayers and evaporation processes taking place during annealing of the
      uncapped monolayer dopant source positioned in proximity, however, without making
      physical contact with the target SC surface. We present a two-step annealing
      procedure that allows the study of the dopant monolayer fragmentation and
      evaporation stages and quantification of the doping levels obtained during each
      step. We demonstrate the application of R-MLD for achieving a large-scale direct
      patterning of silicon substrates with sharp doping profiles. The direct dopant
      patterning is obtained without applying lithographic processing steps to the
      target substrate. The noncontact doping process, monolayer decomposition, and
      fragment evaporation were studied using thermogravimetric analysis coupled with
      mass spectrometry and sheet resistance measurements. The doped patterns were
      characterized using scanning electron microscopy, scanning capacitance
      microscopy, and time-of-flight secondary ion mass spectroscopy.

PMID- 28502173
TI  - Isolated Single-Atom Pd Sites in Intermetallic Nanostructures: High Catalytic
      Selectivity for Semihydrogenation of Alkynes.
AB  - Improving the catalytic selectivity of Pd catalysts is of key importance for
      various industrial processes and remains a challenge so far. Given the unique
      properties of single-atom catalysts, isolating contiguous Pd atoms into a single
      Pd site with another metal to form intermetallic structures is an effective way
      to endow Pd with high catalytic selectivity and to stabilize the single site with
      the intermetallic structures. Based on density functional theory modeling, we
      demonstrate that the (110) surface of Pm3m PdIn with single-atom Pd sites shows
      high selectivity for semihydrogenation of acetylene, whereas the (111) surface of
      P4/mmm Pd3In with Pd trimer sites shows low selectivity. This idea has been
      further validated by experimental results that intermetallic PdIn nanocrystals
      mainly exposing the (110) surface exhibit much higher selectivity for acetylene
      hydrogenation than Pd3In nanocrystals mainly exposing the (111) surface (92% vs
      21% ethylene selectivity at 90  degrees C). This work provides insight for
      rational design of bimetallic metal catalysts with specific catalytic properties.

PMID- 28502174
TI  - Bimetallic Au/Ag Core-Shell Superstructures with Tunable Surface Plasmon
      Resonance in the Near-Infrared Region and High Performance Surface-Enhanced Raman
      Scattering.
AB  - Due to the larger surface area and the synergistic effects between two noble
      metals, the bimetallic superstructures exhibit enhanced distinctive optical,
      catalytic, and photothermal performances and surface-enhanced Raman scattering
      (SERS) "hot-spot" effect, and thus have attracted great interest in various
      applications. Compared with the common Pd, Pt hierarchical structures coated onto
      Au nanoparticles (NPs), easily synthesized via fast autocatalytic surface growth
      arising from intrinsic properties of Pd and Pt metals, precisely controlling the
      hierarchical Ag growth onto Au NPs is rarely reported. In our present study, the
      reducing agent dopamine dithiocarbamate (DDTC) was covalently capped onto the
      first metal core (Au) to delicately control the growth model of the second metal
      (Ag). This results in heterogeneous nucleation and growth of Ag precursor on the
      surface of Au nanorods (NRs), and further formation of cornlike bimetallic Au/Ag
      core-shell superstructures, which usually cannot be achieved from traditional
      epitaxial growth. The thickness of the hierarchical Ag shell was finely tuned in
      a size range from 8 to 22 nm by simply varying the amount of the ratio between Ag
      ions and DDTC capped on Au NR core. The tunable Ag shell leads to anisotropic
      bimetallic Au/Ag core-shell superstructures, displaying two distinctive plasmonic
      resonances in the near-infrared region (NIR). In particular, the longitudinal
      surface plasmon resonance exhibits a broadly tunable range from 840 to 1277 nm.
      Additionally, the rich hot spots from obtained Au/Ag superstructures
      significantly enhance the SERS performance.

PMID- 28502175
TI  - London Dispersion Enables the Shortest Intermolecular Hydrocarbon H...H Contact.
AB  - Neutron diffraction of tri(3,5-tert-butylphenyl)methane at 20 K reveals an
      intermolecular C-H...H-C distance of only 1.566(5) A, which is the shortest
      reported to date. The compound crystallizes as a C3-symmetric dimer in an unusual
      head-to-head fashion. Quantum chemical computations of the solid state at the HSE
      3c level of theory reproduce the structure and the close contact well (1.555 A at
      0 K) and emphasize the significance of packing effects; the gas-phase dimer
      structure at the same level shows a 1.634 A C-H...H-C distance. Intermolecular
      London dispersion interactions between contacting tert-butyl substituents
      surrounding the central contact deliver the decisive energetic contributions to
      enable this remarkable bonding situation.

PMID- 28502176
TI  - Effect of Glutathione on the Taste and Texture of Type I Sourdough Bread.
AB  - Type I sourdough fermentations with Lactobacillus sanfranciscensis as predominant
      organism accumulate reduced glutathione through glutathione reductase (GshR)
      activity of L. sanfranciscensis. Reduced glutathione acts as chain terminator for
      gluten polymerization but is also kokumi-active and may thus enhance bread taste.
      This study implemented a type I model sourdough fermentations to quantitate
      glutathione accumulation sourdough, bread dough, and bread and to assess the
      effect of L. sanfranciscensis GshR on bread volume by comparison of L.
      sanfranciscensis and an isogenic strain devoid of GshR. L. sanfranciscensis
      sourdough accumulated the highest amount of reduced glutathione during proofing.
      Bread produced with the wild type strain had a lower volume when compared to the
      gshR deficient mutant. The accumulation of gamma-glutamyl-cysteine was also
      higher in L. sanfranciscensis sourdoughs when compared to doughs fermented with
      the gshR mutant strain. The accumulation of reduced glutathione in L.
      sanfranciscensis bread did not enhance the saltiness of bread.

PMID- 28502177
TI  - Leveraging Colloidal Aggregation for Drug-Rich Nanoparticle Formulations.
AB  - While limited drug loading continues to be problematic for chemotherapeutics
      formulated in nanoparticles, we found that we could take advantage of colloidal
      drug aggregation to achieve high loading when combined with polymeric excipients.
      We demonstrate this approach with two drugs, fulvestrant and pentyl-PABC
      doxazolidine (PPD; a prodrug of doxazolidine, which is a DNA cross-linking
      anthracycline), and two polymers, polysorbate 80 (UP80) and poly(d,l-lactide-co-2
      methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (PLAC-PEG; a
      custom-synthesized, self-assembling amphiphilic polymer). In both systems, drug
      loaded nanoparticles had diameters < 200 nm and were stable for up to two days in
      buffered saline solution and for up to 24 h in serum-containing media at 37 
      degrees C. While colloidal drug aggregates alone are typically unstable in saline
      and serum-containing media, we attribute the colloid stability observed herein to
      the polymeric excipients and consequent decreased protein adsorption. We expect
      this strategy of polymer-stabilized colloidal drug aggregates to be broadly
      applicable in delivery formulations.

PMID- 28502179
TI  - Self-Propelled Motion of Monodisperse Underwater Oil Droplets Formed by a
      Microfluidic Device.
AB  - We evaluated the speed profile of self-propelled underwater oil droplets
      comprising a hydrophobic aldehyde derivative in terms of their diameter and the
      surrounding surfactant concentration using a microfluidic device. We found that
      the speed of the oil droplets is dependent on not only the surfactant
      concentration but also the droplet size in a certain range of the surfactant
      concentration. This tendency is interpreted in terms of combination of the oil
      and surfactant affording spontaneous emulsification in addition to the Marangoni
      effect.

PMID- 28502178
TI  - Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct
      Phenotypes in Streptococcus mutans Biofilms.
AB  - The oral microbiome is a dynamic environment inhabited by both commensals and
      pathogens. Among these is Streptococcus mutans, the causative agent of dental
      caries, the most prevalent childhood disease. Carolacton has remarkably specific
      activity against S. mutans, causing acid-mediated cell death during biofilm
      formation; however, its complex structure limits its utility. Herein, we report
      the diverted total synthesis and biological evaluation of a rationally designed
      library of simplified analogs that unveiled three unique biofilm phenotypes
      further validating the role of natural product synthesis in the discovery of new
      biological phenomena.

PMID- 28502180
TI  - Metal Nanoparticle Growth within Clay-Polymer Nacre-Inspired Materials for
      Improved Catalysis and Plasmonic Detection in Complex Biofluids.
AB  - Recent studies have shown that layered silicate clays can be used to form a nacre
      like bioinspired layered structure with various polymer fillers, leading to
      composite films with good material strength, gas-barrier properties, and high
      loading capacity. We go one step further by in situ growing metal nanoparticles
      in nacre-like layered films based on layered silicate clays, which can be used
      for applications in plasmonic sensing and catalysis. The degree of anisotropy of
      the nanoparticles grown in the film can be controlled by adjusting the ratio of
      clay to polymer or gold to clay and reducing agent concentration, as well as
      silver overgrowth, which greatly enhances the surface enhanced Raman scattering
      activity of the composite. We show the performance of the films for SERS
      detection of bacterial quorum sensing molecules in culture medium, and catalytic
      properties are demonstrated through the reduction of 4-nitroaniline. These films
      serve as the first example of seedless, in situ nanoparticle growth within nacre
      mimetic materials, and open the path to basic research on the influence of
      different building blocks and polymeric mortars on nanoparticle morphology and
      distribution, as well as applications in catalysis, sensing, and antimicrobial
      surfaces using such materials.

PMID- 28502181
TI  - Rapid Nanogram Scale Screening Method of Microarrays to Evaluate Drug-Polymer
      Blends Using High-Throughput Printing Technology.
AB  - A miniaturized, high-throughput assay was optimized to screen polymer-drug solid
      dispersions using a 2-D Inkjet printer. By simply printing nanoliter amounts of
      polymer and drug solutions onto an inert surface, drug/polymer microdots of
      tunable composition were produced in an easily addressable microarray format. The
      amount of material printed for each dried spot ranged from 25 ng to 650 ng. These
      arrays were used to assess the stability of drug/polymer dispersions with respect
      to recrystallization, using polarized light microscopy. One array with a panel of
      6 drugs formulated at different ratios with a poly(vinylpyrrolidone-vinyl
      acetate) (PVPVA) copolymer was developed to estimate a possible bulk (gram-scale)
      approximation threshold from the final printed nanoamount of formulation. Another
      array was printed at a fixed final amount of material to establish a literature
      comparison of one drug formulated with different commercial polymers for
      validation. This new approach may offer significant efficiency in pharmaceutical
      formulation screening, with each experiment in the nanomicro-array format
      requiring from 3 up to 6 orders of magnitude lower amounts of sample than
      conventional screening methods.

PMID- 28502182
TI  - Isotope-Edited Infrared Spectroscopy for Efficient Discrimination between
      Pharmaceutical Salts and Cocrystals.
AB  - Isotope-edited infrared spectroscopy using carboxylic acids selectively labeled
      with 13C is proposed herein for the efficient discrimination of pharmaceutical
      salts and cocrystals, whereby proton-transfer probe vibrations are highlighted by
      isotope shifts. This new technique can accurately discriminate even a confusing
      salt from a cocrystal for the traditional method, highlighting the diagnostic
      peaks. In addition, the established technique also provided the OH in-plane
      bending vibrations corresponding to intermolecular hydrogen bonding at the
      carbonyl oxygens of the cocrystals. The technique will accelerate the
      discrimination, which is a critical process in cocrystal development.

PMID- 28502183
TI  - Fabrication and Microscopic and Spectroscopic Characterization of Planar,
      Bimetallic, Micro- and Nanopatterned Surfaces.
AB  - Micropatterns and nanopatterns of gold embedded in silver and titanium embedded
      in gold have been prepared by combining either photolithography or electron-beam
      lithography with a glue-free template-stripping procedure. The obtained patterned
      surfaces have been topographically characterized using atomic force microscopy
      and scanning electron microscopy, showing a very low root-mean-square roughness
      (<0.5 nm), high coplanarity between the two metals (maximum height difference ~ 2
      nm), and topographical continuity at the bimetallic interface. Spectroscopic
      characterization using X-ray photoelectron spectroscopy (XPS), time-of-flight
      secondary-ion mass spectrometry (ToF-SIMS), and Auger electron spectroscopy (AES)
      has shown a sharp chemical contrast between the two metals at the interface for
      titanium patterns embedded in gold, whereas diffusion of silver into gold was
      observed for gold patterns embedded in silver. Surface flatness combined with a
      high chemical contrast makes the obtained surfaces suitable for applications
      involving functionalization with molecules by orthogonal adsorption chemistries
      or for instrumental calibration. The latter possibility has been tested by
      determining the image sharpness and the analyzed area on circular patterns of
      different sizes for each of the spectroscopic techniques applied for
      characterization.This is the first study in which the analyzed area has been
      determined using XPS and AES on a flat surface, and the first example of a method
      for determining the analyzed area using ToF-SIMS.

PMID- 28502185
TI  - Characteristics, Management, and Results of Out-of-Hospital Cardiac Arrest (OHCA)
      With or Without ST-Segment Elevation Myocardial Infarction (STEMI).

PMID- 28502184
TI  - Promoting community malaria control in rural Myanmar through an active community
      participation program using the participatory learning approach.
AB  - INTRODUCTION: Malaria is prevalent in more than 80% of townships in Myanmar. The
      National Malaria Control Programme (NMCP) has been implementing community-based
      malaria control programs nationwide. However, these programs are mostly developed
      and directed by health authorities, while communities are passively involved.
      This study aimed to increase community participation in malaria control and
      promote community malaria control knowledge and practice in rural Myanmar.
      METHODS: A community-based study, which employed a mixed method approach,
      collecting data quantitatively and qualitatively, was conducted in two rural
      villages. The study implemented an active community participation program (ACPP)
      using the participatory learning approach in a village (ACPP village) but only
      routine malaria control was given in another village (non-ACPP village). All
      households with 142 and 96 household representatives from ACPP and non-ACPP
      villages participated in baseline and endline surveys. The ACPP was evaluated by
      process and outcome indicators. A spider gram analysis using five process
      indicators was applied to evaluate the process of the ACPP. Community
      participation status in malaria control activities and level of community malaria
      knowledge and practice were determined as outcomes of the ACPP. RESULTS: The
      spider gram analysis showed that three indicators (needs assessment and planning,
      leadership and resource mobilization) gained a score of 4, the organization
      indicator a score of 5 and the management and evaluation indicator a score of 3.
      The outcome indicators of the program at 6 months showed that the community
      participation in malaria control activities in the ACPP village had significantly
      increased (6.9% to 49.3%) (<i>p</i><0.001). The program promoted community
      malaria control knowledge and practice in the ACPP village. The mean scores of
      knowledge, perception, preventive behavior and treatment-seeking behavior were
      increased significantly, from 3.0 to 5.9 (<i>p</i><0.001), 20.1 to 21.0
      (<i>p</i><0.001), 3.4 to 4.2 (<i>p</i><0.001) and 3.1 to 5.6 (<i>p</i><0.001),
      respectively. However, no significant change of outcome indicators was found in
      the non-ACPP village. CONCLUSIONS: The ACPP implemented by community volunteers
      using the participatory learning approach was feasible in community-based malaria
      control. This study suggests several features in the ACPP model that may be
      useful strategies for the implementation of the current NMCP programs in similar
      rural settings; however, the effect of the ACPP over a longer period to ascertain
      the impact of such community participation has yet to be further studied.

PMID- 28502187
TI  - Impaired ventilatory efficiency after closure of atrial or ventricular septal
      defect.
AB  - OBJECTIVES: Atrial and ventricular septal defects are the most common congenital
      heart defects and the closing procedures share important similarities. Generally,
      the postoperative outcome is considered benign, but there is growing concern
      regarding late ventilatory function. Therefore, the aim of this review was to
      describe the ventilatory function in patients with open as well as percutaneously
      or surgically closed atrial and ventricular septal defects. METHODS: We performed
      a search protocol based on the "Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses" (PRISMA) guidelines. A data collection form was specifically
      developed and data were extracted from the included studies by a primary reviewer
      and cross-checked by the secondary reviewer. RESULTS: We found an increasing
      evidence of late impairment in ventilatory efficiency, and despite that
      ventilatory function is commonly normal at rest, abnormalities were disclosed
      during exercise. There are indices that surgical closure plays an important role.
      DISCUSSION: Atrial septal defect and ventricular septal defect patients have
      persisting, long-term impairment in ventilatory efficiency during exercise.
      Although the pathogenesis behind this finding may be multifactorial, there are
      indices that the surgical procedure may play an important role. Nevertheless, the
      literature is this field is sparse, and additional studies are needed.

PMID- 28502186
TI  - Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone
      in prevention of preterm birth in women with a short cervix.
AB  - OBJECTIVE: To compare the efficacy of dydrogesterone, 17-OH progesterone (17OHP)
      and oral or vaginal micronized progesterone with cerclage for the prevention of
      preterm birth in women with a short cervix. METHODS: The study included 95 women
      with singleton gestation and cervical length (CL) <= 25 mm. Among these, 35 women
      were asymptomatic at 15-24 weeks and 60 had symptoms of threatened late
      miscarriage (LM) or preterm delivery (PD) at 15-32 weeks. Patients were
      randomized to receive dydrogesterone, 17OHP or oral/vaginal micronized
      progesterone; after one week of therapy 15 women underwent cerclage. RESULTS:
      Efficacy of vaginal progesterone (VP) for the prevention of preterm birth reached
      94.1%. In asymptomatic women pregnancy outcomes were comparable to cerclage. In
      women with threatened LM/PD, combination therapy with VP, indomethacin and
      treatment of bacterial vaginosis (BV) with the subsequent use VP until 36 weeks
      together with CL monitoring significantly decreased the rate of preterm birth (RR
      0.01; 0.0001-0.24) and low birth weight (LBW) (RR 0.04; 0.01-0.96). CL increase
      during the first week of treatment with a subsequent plateau phase indicated
      treatment efficacy. Dydrogesterone, 17OHP, and micronized oral progesterone (OP)
      were associated with PD in 91.7% of women. CONCLUSIONS: Combination management
      strategy including VP significantly benefits pregnancy outcomes in women with a
      short cervix compared with cerclage. Dydrogesterone, 17OHP, and OP were not found
      to be efficacious.

PMID- 28502188
TI  - Surgical site infection after cesarean delivery: incidence and risk factors at a
      US academic institution.
AB  - PURPOSE: To identify the rate of surgical site infection (SSI) after Cesarean
      delivery (CD) and determine risk factors predictive for infection at a large
      academic institution. METHODS: This was a retrospective cohort study in women
      undergoing CD during 2013. SSIs were defined by Centers for Disease Control (CDC)
      criteria. Chi square and t-tests were used for bivariate analysis and
      multivariate logistic regression was used to identify SSI risk factors. RESULTS:
      In 2419 patients, the rate of SSI was 5.5% (n = 133) with cellulitis in 4.9% (n =
      118), deep incisional infection in 0.6% (n = 15) and intra-abdominal infection in
      0.3% (n = 7). On multivariate analysis, SSI was higher among CD for labor arrest
      (OR 2.4; 95%CI 1.6-3.5; p <.001). Preterm labor (OR 2.8; 95%CI 1.3-6.0; p = .01)
      and general anesthesia (OR 4.4; 95%CI 2.0-9.8; p = .003) were predictive for SSI.
      Increasing BMI (OR 1.1; 95%CI 1.05-1.09; p = .02), asthma (OR 1.9; 95%CI 1.1-3.2;
      p = .02) and smoking (OR 1.9; 95%CI 1.1-3.2; p = .02) were associated with
      increased SSI. CONCLUSIONS: Several patient and surgical variables are associated
      with increased rate of SSI after CD. Identification of risk factors for SSI after
      CD is important for targeted implementation of quality improvement measures and
      infection control interventions.

PMID- 28502190
TI  - Two rare risk factors for post-partum haemorrhage: a case report of a carrier of
      severe haemophilia A with a uterine arteriovenous malformation.

PMID- 28502189
TI  - Long-term outcomes of infliximab treatment and predictors of response in 195
      patients with ulcerative colitis: a hospital-based cohort study from Korea.
AB  - BACKGROUND: Large-scale studies regarding the long-term efficacy of infliximab
      (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are
      lacking. STUDY: We analyzed the long-term outcomes of IFX in 195 Korean UC
      patients who received scheduled IFX treatments at Asan Medical Center. IFX
      failure was defined as IFX discontinuation due to colectomy or non-response to
      IFX, and additionally UC-related hospitalization or a need for rescue
      corticosteroids during the course of IFX. RESULTS: Between December 2006 and
      October 2016, a total of 3101 infusions of IFX were administered to 195 patients
      over a median period of 21 months. At the end of the follow-up, 86 patients
      (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%)
      patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients,
      17.9%) or other reasons such as adverse events or patients' preferences (15
      patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during
      follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC
      related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The
      survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5
      years. In a multivariate regression analysis, cytomegalovirus colitis within 3
      months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57;
      95% confidence interval 1.04-2.37; p = .032). CONCLUSIONS: The long-term efficacy
      of IFX in a large, real-life cohort of Korean UC patients appears to be
      comparable to that in previously published Western studies.

PMID- 28502191
TI  - A novel mutation in ALS2 associated with severe and progressive infantile onset
      of spastic paralysis.
AB  - Infantile onset ascending spastic paralysis (IAHSP) is a type of recessively
      inherited spastic paraplegia. We investigated the clinical and genetic cause of a
      recessively inherited disorder in two siblings manifesting severe spasticity in
      the lower limbs which hindered their gait. A novel homozygous nonsense mutation
      c.1918 C > T (p.Arg640*) was identified after whole-exome sequencing within ALS2
      in the DNA of both patients. The obligate carriers were heterozygous for the
      mutation and other unaffected members were homozygous for the wild type allele.
      The variant was absent from 100 control chromosomes and all public databases.
      This report extends the allelic heterogeneity of ALS2 mutations and emphasizes
      the importance of genetic testing for diagnosis of pediatric disorders.

PMID- 28502192
TI  - Short and long-term outcomes of Streptococcus pyogenes pneumonia managed in the
      intensive care unit.

PMID- 28502194
TI  - Spontaneous lumbar spinal subdural hematoma: a case report.
AB  - Spinal subdural hematoma (SSDH) is an uncommon disease causing acute onset of
      spinal disorder. Several causes of SSDH have been reported, but reports of
      spontaneous occurrence of SSDH are limited.

PMID- 28502193
TI  - Early-onset obesity and food restriction alter hepatocyte metabolism in adult
      Wistar rats.
AB  - CONTEXT: Caloric restriction (CR) is suggested for overweight control. OBJECTIVE:
      Systemic and liver glucose metabolism in the reduced-litter (RL) rat model under
      30% CR was investigated. MATERIALS AND METHODS: Newborn litters were organised in
      control (G9); RL with free diet (G3L); and RL with CR (G3R). Assessments were
      made at the age of 90 d. RESULTS: Higher liver glycogen content and changes in
      systemic glucose handling were found in the RL groups. Hepatocyte glucose
      metabolism was similar in groups G9 and G3L, but basal glucose production and
      glycogenolysis were higher, while gluconeogenesis and basal glycolysis were lower
      in the G3R. Urea production was lower in the RL groups. DISCUSSION: The altered
      glucose handling of the RL adult rats was not reversed by moderate (30%) CR.
      Hepatocyte glucose and nitrogen metabolism were changed by both early overfeeding
      and current feeding conditions. CONCLUSIONS: RL and CR alter systemic and liver
      glucose metabolism.

PMID- 28502195
TI  - Increase of resistance to fluoroquinolone and retained susceptibility to
      macrolides of Campylobacter isolates in Croatia.

PMID- 28502196
TI  - Pendulum and modified pendulum appliances for maxillary molar distalization in
      Class II malocclusion - a systematic review.
AB  - OBJECTIVE: The main purpose of the present systematic review was to evaluate the
      quantitative effects of the pendulum appliance and modified pendulum appliances
      for maxillary molar distalization in Class II malocclusion. MATERIALS AND
      METHODS: Our systematic search included MEDLINE, EMBASE, CINAHL, PsychINFO,
      Scopus and key journals and review articles; the date of the last search was 30
      January 2017. We graded the methodological quality of the studies by means of the
      Quality Assessment Tool for Quantitative Studies, developed for the Effective
      Public Health Practice Project (EPHPP). RESULTS: In total, 203 studies were
      identified for screening, and 25 studies were eligible. The quality assessment
      rated four (16%) of the study as being of strong quality and 21 (84%) of these
      studies as being of moderate quality. The pendulum appliances showed mean molar
      distalization of 2-6.4 mm, distal tipping of molars from 6.67 degrees  to 14.50
      degrees  and anchorage loss with mean premolar and incisor mesial movement of
      1.63-3.6 mm and 0.9-6.5 mm, respectively. The bone anchored pendulum appliances
      (BAPAs) showed mean molar distalization of 4.8-6.4 mm, distal tipping of molars
      from 9 degrees  to 11.3 degrees  and mean premolar distalization of 2.7-5.4 mm.
      CONCLUSIONS: Pendulum and modified pendulum appliances are effective in molar
      distalization. Pendulum appliance with K-loop modification, implant supported
      pendulum appliance and BAPA significantly reduced anchorage loss of the anterior
      teeth and distal tipping of the molar teeth.

PMID- 28502198
TI  - Prevalence of dentin hypersensitivity among the residents of Xi'an city, China.
AB  - OBJECTIVE: To investigate the prevalence and intra-oral distribution of dentine
      hypersensitivity (DH) and to evaluate the related risk factors. MATERIAL AND
      METHODS: A total of 1320 subjects, aged between 20 and 69 years old, were
      selected from six communities in the urban areas of Xi'an, China. The data were
      collected by conducting individual interviews using a standard questionnaire;
      then, the clinical examination was performed for patients who reported about the
      discomforts they felt in their teeth when subjected to chemical, mechanical and
      thermal stimuli. Dentine hypersensitivity (DH) was diagnosed by a subject short,
      sharp pain in response to a blast of cold air from a triple syringe. RESULTS:
      While replying to the questionnaire, 445 subjects reported about signs of
      discomfort in the teeth. DH was diagnosed in 336 persons by clinic examination.
      Thus, the overall prevalence of DH was 33.7% in the questionnaire and 25.5% in
      the intraoral test. The prevalence of DH was higher in females (33.8%) than in
      males (22.2%). Furthermore, we found that the prevalence of DH was highest in the
      age group of 50-59 years (39.3%). The most common initiation factors were acid
      (37.7%) followed by cold stimuli (35.8%). In general, most subjects with
      sensitive teeth had a higher educational background. CONCLUSIONS: The prevalence
      of DH was 25.5% in the population of Xi'an City in China. More emphasis should
      give to middle-aged and old females while planning oral health intervention
      campaigns. In addition, premolars and cervical surfaces should be examined for
      the prevention of DH.

PMID- 28502197
TI  - Effect of maternal age on spontaneous abortion during the first trimester in
      Northeast China.
AB  - OBJECTIVE: We aimed to determine the relationship between fetal chromosomal
      abnormalities and maternal age among spontaneous first trimester abortions in
      women in Northeast China. METHODS: We evaluated 497 chorionic villi samples from
      patients with a history of spontaneous abortion during the first trimester. We
      divided the samples into five groups according to the maternal age: <25, 25-29,
      30-34, 35-39, and >=40 years. We identified chromosomal abnormalities by
      fluorescence in situ hybridization. RESULTS: Among the 497 chorionic samples of
      spontaneous abortion, 180 (36.22%) had fetal chromosomal abnormalities. Patients
      aged >=40 years had a significantly higher percentage (60.61%) of fetal
      chromosomal abnormalities compared with the other groups. More women in the >=40
      and 35- to 39-year groups had a history of three consecutive miscarriages and 10
      kinds of abnormalities. The most frequent aneuploidy was trisomy 22, followed by
      trisomy 16. CONCLUSIONS: These results revealed that the kinds of fetal
      abnormalities, numbers of abortions, and chromosomal abnormality rates increased
      with increasing maternal age. The most common trisomy types in spontaneous
      abortions were closely related to maternal age. We hypothesize whether the larger
      probability of chromosomal abnormalities is due to increased mutation rate with
      maternal age, or due to a worse in-utero conditions.

PMID- 28502199
TI  - Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with
      synergistic antitumor efficiency.
AB  - Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as
      a drug carrier and enhancer for cancer therapy. CE-based combination therapy was
      prone to be attractive in cancer therapy. In our previous study, the combination
      of CE and docetaxel (DTX) was proved to be an effective strategy for cancer
      therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based
      nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic
      therapeutic effect. The enhanced delivery and synergistic therapeutic effect of
      DTX-loaded CE-LNS (CE + DTX-LNS) were evaluated. CE + DTX-LNS exhibited spherical
      or ellipsoidal shape, uniform particle size distribution (108.1 +/- 3.8 nm),
      sustained release characteristics and good stability in vitro. Notably, CE + DTX
      LNS could effectively co-localize CE and DTX into same tumor cell and
      subsequently play synergistic cell damage effect compared with CE-LNS + DTX-LNS
      (p < 0.05). The in vivo fluorescence imaging results showed that CE + DTX-LNS
      could effectively prolong the in vivo circulation time and enhance the
      accumulation in tumor sites. Moreover, the antitumor efficacy of CE + DTX-LNS
      observed in B16 murine melanoma model was 93.94 +/- 2.77%, significantly higher
      than that of CE-LNS, DTX-LNS, Duopafei(r) (p < 0.01) and CE-LNS + DTX-LNS (p <
      0.05), respectively, demonstrating that co-delivery of CE and DTX into same tumor
      cell was the basis for enhanced synergistic therapeutic effect. Furthermore,
      histological examination of Blank-LNS showed no visible tissue toxicity compared
      to normal saline. Consequently, CE-LNS could effectively delivery DTX and CE +
      DTX-LNS exhibit synergistic inhibition of tumor growth due to the co-localization
      of CE and DTX. CE-LNS hold great potential to be an appropriate carrier for CE
      based combination chemotherapy.

PMID- 28502200
TI  - Foetal premature atrial contractions during the second and third trimester are
      not associated with foetal breathing.
AB  - Foetal premature atrial contractions (PACs) are the most commonly encountered and
      also the most benign foetal arrhythmia. A retrospective cohort study was
      conducted with the objective to assess whether the presence of foetal breathing
      was associated with the presence of foetal PACs. A further objective was to
      evaluate whether this association would affect neonatal outcomes at a high volume
      referral centre. The diagnosis of PACs was based on the observation of a
      premature atrial contraction followed by a ventricular contraction on ultrasound
      myocardial M-mode. Trained ultrasonographers documented in the ultrasound report
      whether or not foetal breathing was present with PACs. 91 exams were identified,
      which included 75 individual pregnancies. Six women were identified who had
      foetal PACs associated with foetal breathing on ultrasound evaluation. Foetuses
      with PACs did not differ between the associated breathing and no-associated
      breathing groups with respect to maternal age, parity, mode of delivery,
      gestational age at delivery or birthweight. This study reaffirms that isolated
      PACs are a benign finding. Furthermore, it adds to the pool of literature on
      foetal PACs in that it is not associated with abnormal pregnancy outcomes
      regardless of the presence or absence of foetal breathing. Impact statement *
      What is already known on this subjectSince foetal breathing can effect Doppler
      ultrasound assessment of the foetal cardiovascular system, it is reasonable to
      consider that it may impact conditions such as foetal arrhythmias. * What the
      results of this study addFoetal breathing does not impact on the presence of
      premature atrial contractions. * What the implications are of these findings for
      clinical practice and/or further researchFoetal breathing is not associated with
      the finding of foetal premature atrial contractions.

PMID- 28502201
TI  - Prediction of chorioamnionitis in cases of intraamniotic infection by ureaplasma
      urealyticum in women with very preterm premature rupture of membranes or preterm
      labour.
AB  - OBJECTIVES: First, to determinate the frequency of chorioamnionitis and funisitis
      in cases of intramniotic detection of Ureaplasma urealyticum. Second, to assess
      the predictive capability of some biological markers in the amniotic fluid of
      these women to predict histological inflammation. SUBJECTS AND METHODS: We
      prospectively studied 20 cases of women with premature rupture of membranes or
      preterm labour (PROM) or preterm labour and intraamniotic detection of Ureaplasma
      urealyticum. Gestational age at admission was 26.74 +/- 2.53 weeks. Amniotic
      fluid concentrations of IL18, IL 2, IL4, IL6, IL10, IL12, TNF-alpha, IFN-g, and
      MMP-8 were measured by the Multiplex method. Amniotic fluid glucose and leukocyte
      count were also measured by standard methods. Placental detailed histological
      studies were performed. Student's t-test, forward stepwise conditional binary
      logistic regression analysis and ROC curves were used. RESULTS: Histological
      chorioamnionitis was present in 45% of cases (9/20) and funisitis just in 15%
      (3/20). Interleukins 6, 8, 12, MMP-8, and leukocyte count were significantly
      elevated in cases of histological inflammation, defined as choriamnionitis or
      chorioamniotis + funisitis (p = .007, .03, .01, .03, .03, respectively) while
      glucose was decreased (p = .04). Binary logistic regression for the prediction of
      inflammation showed a high predictive value (R2 = .66, p = .002) including in the
      equation only the IL6 value. CONCLUSIONS: A significant percentage of cases with
      intraamniotic detection of Ureaplasma urealyticum shows no pathological signs of
      histological inflammation. Concentration of Interleukin 6 in amniotic fluid can
      be useful for the diagnosis of subclinical chorioamnionitis in these cases.

PMID- 28502204
TI  - Alu insertion polymorphisms in the African Sahel and the origin of Fulani
      pastoralists.
AB  - BACKGROUND: The origin of Western African pastoralism, represented today by the
      Fulani nomads, has been a highly debated issue for the past decades, and has not
      yet been conclusively resolved. AIM: This study focused on Alu polymorphisms in
      sedentary and nomadic populations across the African Sahel to investigate
      patterns of diversity that can complement the existing results and contribute to
      resolving issues concerning the origin of West African pastoralism. SUBJECTS AND
      METHODS: A new dataset of 21 Alu biallelic markers covering a substantial part of
      the African Sahel has been analysed jointly with several published North African
      populations. RESULTS: Interestingly, with regard to Alu variation, the
      relationship of Fulani pastoralists to North Africans is not as evident as was
      earlier revealed by studies of uniparental loci such as mtDNA and NRY. Alu
      insertions point rather to an affinity of Fulani pastoralists to Eastern Africans
      also leading a pastoral lifestyle. CONCLUSIONS: It is suggested that contemporary
      Fulani pastoralists might be descendants of an ancestral Eastern African
      population that, while crossing the Sahara in the Holocene, admixed slightly with
      a population of Eurasian (as evidenced by uniparental polymorphisms) ancestry. It
      seems that, in the Fulani pastoralists, Alu elements reflect more ancient genetic
      relationships than do uniparental genetic systems.

PMID- 28502202
TI  - Cooking processes increase bioactive compounds in organic and conventional green
      beans.
AB  - The influence of cooking methods on chlorophyl, carotenoids, polyamines,
      polyphenols contents and antioxidant capacity were analyzed in organic and
      conventional green beans. The initial raw material had a higher content of
      chlorophyl and total phenolics in conventional green beans, whereas organic
      cultive favored flavonoid content and antioxidant capacity. Polyamines and
      carotenoids were similar for the two crop systems. After the cooking process,
      carotenoids (beta-carotene, lutein and zeaxanthin) increased. Microwave heating
      favored the enhancement of some polar compounds, whereas pressure cooking favored
      carotenoids. When we used the estimation of the radical scavenging activity by
      electron spin resonance (ESR) spectroscopy, a reduction of the DPPH radical
      signal in the presence of green bean extracts was observed, regardless of the
      mode of cultivation. The highest reduction of the ESR signal ocurred for
      microwave cooking in organic and conventional green beans, indicating a higher
      availability of antioxidants with this type of heat treatment.

PMID- 28502203
TI  - Chewing gum improves postoperative recovery of gastrointestinal function after
      cesarean delivery: a systematic review and meta-analysis of randomized trials.
AB  - OBJECTIVE: To examine whether chewing gum hastens the return of gastrointestinal
      function after a cesarean delivery. METHODS: All randomized controlled trials
      comparing the use of chewing gum in the immediate postoperative recovery period
      (i.e. intervention group) with a control group were included in the meta
      analysis. The primary outcome was the time to first flatus in hours. Meta
      analysis was performed using the random effects model of DerSimonian and Laird,
      to produce summary treatment effects in terms of mean difference (MD) or relative
      risk (RR) with 95% confidence interval (CI). RESULTS: Seventeen trials, including
      3041 women, were analyzed. Trials were of moderate to low quality with different
      inclusion criteria. In most of the included trials chewing gum was given right
      after delivery, three times a day for 30 min each and until the first flatus.
      Women who were randomized to the chewing gum group had a significantly lower mean
      time to first flatus (MD - 6.49 h, 95%CI -8.65 to -4.33), to first bowel sounds
      (MD - 8.48 h, 95%CI -9.04 to -7.92), less duration of stay (MD - 0.39 days, 95%CI
      -0.78 to -0.18), lower time to first feces (MD - 9.57 h, 95% CI -10.28 to 8.87)
      and to the first feeling of hunger (MD - 2.89 h, 95%CI -4.93 to -0.85), less
      number of episodes of nausea or vomiting (RR 0.33, 95%CI 0.12 to 0.87), less
      incidence of ileus (RR 0.39, 95%CI 0.19 to 0.80) and significantly higher
      satisfaction. CONCLUSIONS: Gum chewing starting right after cesarean delivery
      three times a day for about 30 min until the first flatus is associated with
      early recovery of bowel motility. As this is a simple, generally inexpensive
      intervention, providers should consider implementing cesarean postoperative care
      with gum chewing.

PMID- 28502205
TI  - Role of mean platelet volume and ischemia modified albumin in evaluation of
      oxidative stress and its association with postnatal complications in infants of
      diabetic mothers.
AB  - Gestational diabetes mellitus (GDM) is accompanied by increased oxidative stress,
      causing many complications to pregnant women and their newborns. We aimed to
      determine cord blood levels of mean platelet volume (MPV) and ischemia modified
      albumin (IMA) as a reflection of oxidative stress in babies born to mothers
      suffering from GDM. Eighty pregnant women were enrolled in the study. They were
      divided into two groups: 40 with GDM and 40 healthy matched controls. Each group
      included twenty giving birth by normal vaginal delivery (NVD) and twenty by
      cesarean section (C.S). The MPV and the IMA levels were measured. Complete
      physical examination of babies was done at birth and follow up at age of one
      week. Comparison between infants of diabetic mothers and of healthy mothers
      showed statistically significant difference in the levels of MPV (p < .001) and
      IMA (p = .001). Also, there was a statistically significant difference in MPV (p
      < .001) and IMA (p = .005) between diabetic females who gave birth by NVD and
      C.S. ROC curve analysis showed that IMA and MPV variables were related to the
      postnatal outcomes. MPV and IMA are useful markers of the potential oxidative
      stress in infants of diabetic mothers and of postnatal complications.

PMID- 28502206
TI  - DNA barcoding and phylogenetic analysis of five ascidians (Phlebobranchia)
      distributed in Gulf of Mannar, India.
AB  - DNA barcoding has played a significant role in biodiversity assessment as well as
      its conservation. This technique involves sequencing of mitochondrial marker gene
      including a short COI gene, known as barcode gene. It has proved its efficiency
      in identifying several species and resolving the limitations incurred during
      identification through conventional taxonomy. This study involves the use of DNA
      barcoding of ascidian species belonging to order Phlebobranchia. A total of 14
      individuals, covering two families, three genera and five species, were barcoded.
      COI gene sequences of all the five species were deposited for the first time in
      NCBI as well as BOLD. The NJ tree revealed identical phylogenetic relationship
      among the individuals collected from three different stations. Mean Kimura 2
      parameter (K2P) distances within-species, genus, family and order were 0.08%,
      6.69%, 9.49% and 18.58%, respectively. This result concludes that COI gene
      sequencing is the efficient tool in identifying ascidians of the order
      Phlebobranchia. We report for the first time the COI gene sequences of four
      species of ascidians studied.

PMID- 28502207
TI  - Symptoms in the masticatory system and related quality of life in prospective
      orthognathic patients.
AB  - OBJECTIVE: The aim of this study was to investigate the relation between
      orthognathic patients' self-reported symptoms in the head and neck region and
      their quality of life (QoL). MATERIAL AND METHODS: Participants included were
      consecutive patients (n = 50) referred to the assessment of orthognathic
      treatment need and voluntary first-year university students (n = 29). All
      participants filled in the Orthognathic Quality of Life Questionnaire (OQLQ) and
      a structured diary created by the authors. The median values of Orthognathic
      Quality of Life (OQOL) sum and subscores, satisfaction with oral function and
      number of awakenings were compared between patients and controls. Further,
      correlations between the OQOL sum and subscores, satisfaction with oral function
      and number of awakenings were analyzed. RESULTS: Patients reported significantly
      more symptoms (p = .013) and woke up significantly more often than the controls
      (p = .032). Their OQOL sum scores were significantly higher (indicating a lower
      OQOL) (p = .001), and they were significantly less satisfied with their oral
      function than the controls (p < .001). Among the awakened and not-rested
      patients, the most commonly reported symptoms were pain in the head and/or neck
      region and fatigue and/or stiffness in the jaws. CONCLUSIONS: Experiences of pain
      and discomfort have a significant impact on patients' OQOL and well-being.

PMID- 28502208
TI  - [The prognostic role of extremely high levels of the B-type natriuretic
      prohormone with regard to the in-hospital mortality of patients hospitalized for
      heart failure].
AB  - INTRODUCTION: Patients hospitalized for heart failure have a very high in
      hospital as well as one-year mortality. Natriuretic peptides play both a
      diagnostic and a prognostic role in this disease. Changes of natriuretic peptide
      levels in response to therapy are a well-known prognostic marker. Regarding in
      hospital mortality, however, little is known about the prognostic value of
      extremely high levels of natriuretic peptides measured on admission. AIM: To
      decide whether extremely high levels of B-type natriuretic peptide have a
      prognostic value with regard to in-hospital mortality. METHOD: NT-proBNP levels
      on admission and in-hospital mortality were extracted retrospectively from the
      data of patients treated with heart failure in the cardiology department of the
      Hospital of St. John of God in Budapest. We separately analyzed the data of
      patients hospitalized for heart failure in 2015 with extremely high initial NT
      proBNP levels. The cut-off value in this regard was 10 000 ng/l. We also analyzed
      the comorbidities of these patients. RESULTS: The median NT-proBNP level of those
      patients who survived beyond the index hospital stay in the last 10 years was
      4842 ng/l, whereas the median NT-proBNP level of those 182 patients who died
      during their hospital stay was 10 688 ng/l (p<0.001). In the year 2015, we
      treated 118 patients with an NT-proBNP level above 10 000 ng/l. Thirteen of these
      patients died, which means that their in-hospital mortality exceeded 10%. In
      comparison, the in-hospital mortality of all heart failure patients was 5.8%. The
      difference of median NT-proBNP levels of surviving versus deceased patients in
      this group with extremely high NT-proBNP levels was no longer significant (17 080
      ng/l vs. 19 152 ng/l). CONCLUSIONS: Patients with an NT-proBNP level of >10 000
      ng/l on admission have a significantly higher in-hospital mortality. The
      difference of NT-proBNP levels of surviving versus deceased patients in the group
      with admission NT-proBNP levels >10 000 ng/l is no longer significant. We could
      not identify any etiological factors that would explain these extremely high NT
      proBNP levels or the excess in-hospital mortality. Orv Hetil. 2017; 158(20): 779
      782.

PMID- 28502209
TI  - [Detection of West Nile virus in human samples: follow-up studies during the 2015
      seasonal period].
AB  - INTRODUCTION: West Nile virus, a mosquito-borne viral zoonosis is responsible for
      human infections in Hungary. Laboratory diagnosis is based on serological tests,
      however the application of molecular methods has been appreciated. AIM: The aim
      of the study was to investigate blood, cerebrospinal-fluid and urine samples of
      acutely ill patients and to follow-up PCR positive cases to ascertain the length
      of virus excretion. METHOD: Clinical specimens were examined by indirect
      immunofluorescent, haemagglutination-inhibition, two PCR tests and Sanger
      sequencing. Virus isolation in case of two patients was successful. RESULTS: A
      follow-up study could be carried out in case of 5 patients. Viral nucleic acid
      was detectable in urine even for several weeks after symptom onset and viral RNA
      was present at higher concentration compared with other samples. CONCLUSIONS: PCR
      analysis of urine could provide useful epidemiological and diagnostic
      information. Therefore, it is recommended to collect urine samples in order to
      supplement the serological diagnosis. Orv Hetil. 2017; 158(20): 791-796.

PMID- 28502210
TI  - [Esophageal complications of gastroesophageal reflux disease: consequences or
      defensive reactions?]
AB  - Gastroesophageal reflux disease affects more than 10% of the adult population.
      Most patients can be effectively treated with lifestyle changes and adequate acid
      reducing therapy. However, about 10% of the patients remain symptomatic despite
      treatment and severe complications may develop. Interestingly, some of these
      complications seem to be a sort of defensive mechanism that may either alleviate
      the patient's symptoms or prevent developing further complications. In Barrett's
      esophagus, which can be unambigously considered as a complication of
      gastroesophageal reflux disease, reflux symptoms ruining the quality of life may
      significantly improve, since the metaplastic Barrett epithelium is much more
      resistent to gastric acid, than the normal epithelial lining of the esophagus.
      Furthermore, the motility disorders (hypertensive lower esophageal sphincter,
      achalasia, cricopharyngeal achalasia) and structural changes (Schatzki's ring,
      esophageal stricture, subglottic trachea stenosis), which develop as a
      complication of reflux may help to prevent aspiration that can cause new
      complaints and may lead to further complications. Orv Hetil. 2017; 158(20): 763
      769.

PMID- 28502212
TI  - [Trends in antidiabetic treatment prescribed for patients with type 2 diabetes in
      Hungary between 2001 and 2014 - results from the database analysis of the
      National Health Insurance Fund].
AB  - In the last couple of years, significant developments in antidiabetic treatment
      have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM).
      The aim of this study was to analyze the changes in prescribing patterns of
      glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The
      number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to
      33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in
      2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy
      decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42%
      in this period. The most frequently used drug at first treatment initiation was
      metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors
      were newly administered in 20,362 cases while GLP1-mimetics were newly used by
      4,996 patients in 2014. Five years later after initiating sulfonylurea therapy
      between 2010 and 2014, metformin was more frequently used as second drug (39%)
      than sulfonylurea in patients with previous metformin treatment (22.9%). The
      prescribing patterns of glucose-lowering drugs have changed over time in
      accordance with new guidelines. Further changes in prescribing habits can be
      expected in the near future. Orv Hetil. 2017; 158(20): 770-778.

PMID- 28502213
TI  - [Analysis of mortality and its predictors in patients with contralateral hip
      fracture after femoral neck fracture].
AB  - INTRODUCTION: There is a high mortality with not well understood risk factors
      after the second hip fracture. AIM: Analysis of the 30- and 365-day mortality and
      its risk factors in patients with contralateral hip fracture. METHOD: Patients
      with contralateral hip fracture between 01 Jan 2000 and 31 Dec 2008 were
      identified among those who suffered their primary hip fracture in Hungary in
      2000. Risk factors as age, sex, concomitant and chronic diseases, type of
      fracture and surgery, surgical complications, day of admission were analyzed by
      logistic and Cox regression as well as Kaplan-Meier analysis. RESULTS: There were
      312 eligible patients identified with 8.3 % mortality rate at 30 and with 38,4%
      at 365 days respectively. Significant risk factors for the 30 day mortality were
      intertrochanteric type of fracture (OR: 4.722; HR: 4.129) and non operative
      management (OR: 7.357; HR: 6.317) while for the 365 day mortality those were
      older age (OR:1.070; HR:1.050) and type of surgery (OR: 0.450). CONCLUSION: Age,
      type of fracture and type of surgery proved to be risk factors. There is a need
      to identify further risk factors in order to develop an efficacious prevention
      strategy for the reduction of the mortality after the second hip fractures. Orv
      Hetil. 2017; 158(20): 783-790.

PMID- 28502214
TI  - Giving Our Daughters What We Never Received: African American Mothers Discussing
      Sexual Health With Their Preadolescent Daughters.
AB  - African American girls experience disparate rates of pregnancy and acquisition of
      sexually transmitted infections, including human immunodeficiency virus, when
      compared to their non-Hispanic White counterparts. Among African American girls,
      current pregnancy rates are equal to the national crisis levels of teen pregnancy
      reported in 1990. This qualitative elicitation study was conducted to gain
      insight into the ways in which African American mothers and their daughters,
      between the ages of 9 and 14, communicate about sexual health. Early sexual
      health communication between mothers and daughters is known to enhance the sexual
      health outcomes of girls. A series of four focus groups and three in-depth
      interviews were conducted between July and September 2014. The theory of planned
      behavior was the organizing framework. Theoretical constructs that guided this
      study were attitudes, perceived behavioral control, and subjective norms. Results
      showed that what African American women share with their daughters about sexual
      health stems from their personal faith, values, and experiences. Findings from
      this study can inform interventions to provide support for this understudied
      population. Moreover, there are implications for health-care providers,
      particularly school nurses, who are in an ideal position to help increase
      mothers' self-efficacy to engage in sexual health conversations with their young
      daughters.

PMID- 28502215
TI  - In response to C Walshe, 'The state of play'.

PMID- 28502216
TI  - A retrospective analysis of postoperative recurrence of septated chronic subdural
      haematoma: endoscopic surgery versus burr hole craniotomy.
AB  - OBJECTIVE: To identify the factors associated with Septated chronic subdural
      haematoma (sCSDH) recurrence and to compare the advantages and disadvantages of
      burr hole craniotomy (BHC) and endoscopic surgery (ES) with respect to preventing
      sCSDH recurrence. METHODS: A total of 76 consecutive patients with sCSDH
      underwent BHC or ES in our institution. Their clinical data were retrospectively
      analysed to identify the factors associated with sCSDH recurrence and to evaluate
      the effectiveness of BHC and ES with respect to preventing sCSDH recurrence.
      RESULTS: There were no significant differences in gender, age, Markwalder grade,
      side of haematoma, preoperative mid-line shifts, intervals, clinical features or
      medical histories between the two groups. Bilateral sCSDH was the only factor
      that significantly influenced the sCSDH recurrence rate (RR) (p = 0.001). Male
      gender, age >= 60 years, poor Markwalder grade, preoperative mid-line shifts <=10
      mm, postoperative mid-line shifts >10 mm, neovessels, intervals <=20 days and
      medical histories tended to be associated with sCSDH recurrence. The RRs in the
      BHC and ES groups were 13.7 and 8.7%, respectively. ES eliminated more factors
      associated with recurrence than BHC; however, ES required more surgery time (p <
      0.001) and more medical consumption (p < 0.001) than BHC. CONCLUSIONS: Bilateral
      sCSDH exerted the most significant influence on the sCSDH RR. There was no
      difference between ES and BHC with respect to decreasing the sCSDH RR. However,
      BHC is a more efficient procedure than ES, as it required less surgery time and
      less medical consumption than ES.

PMID- 28502217
TI  - Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA
      (A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.
AB  - OBJECTIVE: The purpose of the present study was to observe the effects of
      hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and
      GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. METHODS:
      A total of 110 healthy adult male Wistar rats were used to generate a model of
      epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected
      from 70 amygdala-kindled rats by testing their response to Phenytoin and
      Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation
      group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8
      rats). A stimulation electrode was implanted into the hippocampus of all of the
      rats. Hip-LFS was administered twice per day in the PRS group for two weeks.
      Simultaneously, amygdala stimulus-induced seizures and afterdischarge were
      recorded. After the hippocampal stimulation was terminated, the brain tissues
      were obtained to determine the GABA (A) receptors by a method of
      immumohistochemistry and a real-time polymerase chain reaction. RESULTS: The
      stages and duration of the amygdala stimulus-induced epileptic seizures were
      decreased in the PRS group. The afterdischarge threshold was increased and the
      duration as well as the afterdischarge frequency was decreased. Simultaneously,
      the GABA (A) expression was significantly increased in the PRS group.
      CONCLUSIONS: Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and
      up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects
      of hippocampal stimulation may be partly achieved by increasing the GABA (A)
      receptor.

PMID- 28502219
TI  - Towards an ethics for telehealth.
AB  - Over the last two decades, a public rationale for the implementation of
      telehealth has emerged at the interplay of specialised literature and political
      orientations. Despite the lack of consistent findings on the magnitude of its
      benefits, telehealth is nowadays presented as a worthy solution both for patients
      and healthcare institutions. Far from denying the potential advantages of
      telehealth, the main objective of this work is to provide a critical assessment
      on the spread of the remote services as a vector of positive transformation of
      contemporary health systems. For pursuing this objective, the EU agenda for the
      promotion of telehealth will be retraced, and the main evidences alleged to
      sustain the implementation of remote care services will be assessed. Furthermore,
      it will be evaluated the attempt made by the European Commission to establish an
      ethical framework for guiding the use of telehealth in daily practice, and a
      roadmap of the most relevant legal and ethical issues posed by the spread of
      telehealth will be traced. In the conclusions, it will be argued that the radical
      transformations induced by this form of technological innovation call on to a
      new, ad hoc ethics through which critically evaluate benefits and implications of
      telehealth services, with a view to keep high the standard of healthcare against
      the economic interests of private stakeholders and ICTs' vendors.

PMID- 28502218
TI  - Recommendations to reduce inequalities for LGBT people facing advanced illness:
      ACCESSCare national qualitative interview study.
AB  - BACKGROUND: Lesbian, gay, bisexual and/or trans (LGBT) people have higher risk of
      certain life-limiting illnesses and unmet needs in advanced illness and
      bereavement. ACCESSCare is the first national study to examine in depth the
      experiences of LGBT people facing advanced illness. AIM: To explore health-care
      experiences of LGBT people facing advanced illness to elicit views regarding
      sharing identity (sexual orientation/gender history), accessing services,
      discrimination/exclusion and best-practice examples. DESIGN: Semi-structured in
      depth qualitative interviews analysed using thematic analysis.
      SETTING/PARTICIPANTS: In total, 40 LGBT people from across the United Kingdom
      facing advanced illness: cancer ( n = 21), non-cancer ( n = 16) and both a cancer
      and a non-cancer conditions ( n = 3). RESULTS: In total, five main themes
      emerged: (1) person-centred care needs that may require additional/different
      consideration for LGBT people (including different social support structures and
      additional legal concerns), (2) service level or interactional (created in the
      consultation) barriers/stressors (including heteronormative assumptions and
      homophobic/transphobic behaviours), (3) invisible barriers/stressors (including
      the historical context of pathology/criminalisation, fears and experiences of
      discrimination) and (4) service level or interactional facilitators (including
      acknowledging and including partners in critical discussions). These all shape
      (5) individuals' preferences for disclosing identity. Prior experiences of
      discrimination or violence, in response to disclosure, were carried into future
      care interactions and heightened with the frailty of advanced illness.
      CONCLUSION: Despite recent legislative change, experiences of discrimination and
      exclusion in health care persist for LGBT people. Ten recommendations, for health
      care professionals and services/institutions, are made from the data. These are
      simple, low cost and offer potential gains in access to, and outcomes of, care
      for LGBT people.

PMID- 28502220
TI  - Dynamic assessment of visual neglect: The Mobility Assessment Course as a
      diagnostic tool.
AB  - INTRODUCTION: Visual neglect is a frequent disorder following stroke and is often
      diagnosed by neuropsychological assessment. However, paper-and-pencil tasks have
      low predictive value as they lack sensitivity to capture neglect in complex,
      dynamic situations, such as activities of daily living. Aims of the current study
      were to assess the feasibility of the Mobility Assessment Course (MAC), a visual
      search multitask, to assess neglect, and its relation with existing neglect
      tasks. METHOD: Stroke patients admitted for inpatient rehabilitation and healthy
      controls were tested with the MAC in different corridors. Participants had to
      move through a corridor, finding and reporting 24 targets attached to the walls.
      In addition, the shape cancellation, line bisection, and Catherine Bergego Scale
      (CBS) were used in order to compare the MAC with existing diagnostic tools for
      neglect. RESULTS: Administering the MAC was feasible, as 112 of 113 patients
      completed the MAC with a median duration of 4.09 min. Depending on the corridor
      where the assessment took place, in 88.5-93.3% of assessments all targets were
      visible. The number of omissions (total and contralesional) and the asymmetry
      score (contralesional-ipsilesional omissions) on the MAC as well as collisions
      and corrections, were higher for patients with neglect than for those without
      neglect. Depending on the neglect task used, 4.0-18.6% of patients without
      neglect on neuropsychological tasks or the CBS showed neglect on the MAC. Vice
      versa, 17.2-29.3% of patients who showed neglect at neuropsychological assessment
      or the CBS did not do so on the MAC. Finally, a moderate to strong positive
      relation was seen between neglect at neuropsychological assessment, the CBS, and
      the MAC. CONCLUSIONS: The MAC is an ecological task in which both quantitative
      and qualitative data on neglect can be collected. In order to assess the presence
      of neglect and neglect severity in a dynamic way, the MAC could be administered
      in conjunction with neuropsychological assessment.

PMID- 28502221
TI  - Reliability of mandibular movement assessments depending on TMD.
AB  - OBJECTIVE: This study determines the effect of temporomandibular disorders (TMD)
      on the reliability of mandibular movement assessments. METHODS: The vertical and
      horizontal jaw movements, as well as overjet and overbite, were measured twice in
      56 consecutively recruited adult subjects with TMD according to the RDC/TMD and
      29 controls without TMD diagnosis by experienced dentists utilizing a millimeter
      ruler. The reliability was determined by intraclass correlation coefficient
      (ICC). RESULTS: Neither statistically nor clinically relevant differences in the
      repeatability between both subgroups could be detected (all p >= 0.077). The
      mouth opening and overjet proved an excellent reliability (ICC 0.85-0.92).
      Overbite and laterotrusion showed good to excellent reliable results (ICC 0.74
      0.82). The second measurement of the vertical jaw movement resulted in
      systematically higher values (p < 0.003). DISCUSSION: The assessment of the
      mandibular movement with a millimeter ruler is a reliable procedure irrespective
      of TMD. To decrease the variances in the mouth opening measurements, the patient
      should be asked beforehand to practice this movement.

PMID- 28502222
TI  - Understanding pain physiology and its application to person with intellectual
      disability.
AB  - The issue of pain warrants attention as, by virtue of having an intellectual
      disability, a person may have associated medical or physical conditions and
      associated factors increasing their risk of pain disorders. People with
      intellectual disability experiencing pain need to be provided with the best
      possible care. The focus of this article is on the exploration of pain:
      physiology and types; manifestations and responses in the context of intellectual
      disability in order to promote effective, knowledgeable assessment and management
      of pain for this client group. Pain is a subjective, complex, physiological and
      psychological phenomenon that can be acute or chronic and may be classified
      according to its cause. Within the experience of pain, the concept of total pain
      describes the physical, psychological, social and spiritual factors that
      influence the experience of pain.

PMID- 28502223
TI  - Investigation of angiogenesis genes with anterior cruciate ligament rupture risk
      in a South African population.
AB  - The angiogenesis-signalling pathway is a physiological response after mechanical
      loading to promote matrix remodelling and thereby maintain tissue homeostasis.
      Studies have shown increased expression of angiogenic molecules in response to
      loading and in ruptured ligaments. Recently, polymorphisms within the vascular
      endothelial growth factor A (VEGFA) and kinase insert-domain receptor (KDR) genes
      were associated with risk of anterior cruciate ligament (ACL) ruptures and
      Achilles tendinopathy in Caucasian study groups. A case-control genetic
      association study was conducted on 100 controls and 98 participants with
      surgically-diagnosed ACL ruptures; of which 51 participants reported non-contact
      mechanism of injury (NON). All participants were genotyped for five functional
      polymorphisms: VEGFA (rs699947, rs1570360, rs2010963) and KDR (rs2071559,
      rs1870377). Haplotypes were inferred. In the male participants, the KDR rs2071559
      AG genotype was significantly over-represented (P = 0.048, OR: 1.90, 95% CI: 1.00
      3.59) in the controls. Furthermore, the GG genotype was significantly under
      represented in the male controls compared to the male ACL group (P = 0.018, OR:
      2.77, 95% CI: 1.17-6.55) and the male NON subgroup (P = 0.013, OR: 3.26, 95% CI:
      1.24-8.58). Haplotype analysis implicated the KDR gene in all participants and in
      male participants separately. Collectively, these results implicate the
      angiogenesis-signalling pathway as a potentially key biological pathway
      contributing to ACL injury susceptibility.

PMID- 28502224
TI  - Diagnosis and treatment of paediatric tuberculosis: An insight review.
AB  - Tuberculosis (TB) is a major public health problem, invading all age groups world
      wide. It is an opportunistic infection affecting the individuals alone or with co
      infections. Childhood TB is a neglected aspect and a significant health problem
      in epidemic areas. It constitutes more than 20% of TB incidence. Pediatric TB
      exists in the shadow of adult TB. The clinicians concentrate on pulmonary
      manifestation of TB, whereas it is a major problem in both pulmonary and extra
      pulmonary infections. The rate of infection with this disease is mostly
      associated with poverty, social disruption and human immunodeficiency virus (HIV)
      infection. The diagnosis of extra-pulmonary TB (EPTB) is more difficult than
      pulmonary TB (PTB). Delayed diagnosis and executive treatment contribute to
      increase in the mortality rate in endemic areas. This article provides the
      evidence-based simple and safe screening method, indicating rapid, highly
      sensitive and specific diagnostic tests for pulmonary and EPTB in children. The
      most important aspect of treatment is the correct course of anti-tubercular
      drugs. This review serves the purpose of quick reference for microbiologists,
      epidemiologists, academicians, students and researchers. It provides guidance
      regarding early diagnosis and treatment accuracy of pediatric TB.

PMID- 28502225
TI  - Genomics of lactic acid bacteria: Current status and potential applications.
AB  - Lactic acid bacteria (LAB) are widely used for the production of a variety of
      foods and feed raw materials where they contribute to flavor and texture of the
      fermented products. In addition, specific LAB strains are considered as probiotic
      due to their health-promoting effects in consumers. Recently, the genome
      sequencing of LAB is booming and the increased amount of published genomics data
      brings unprecedented opportunity for us to reveal the important traits of LAB.
      This review describes the recent progress on LAB genomics and special emphasis is
      placed on understanding the industry-related physiological features based on
      genomics analysis. Moreover, strategies to engineer metabolic capacity and stress
      tolerance of LAB with improved industrial performance are also discussed.

PMID- 28502226
TI  - Stronger interference from distractors in the right hemifield during visual
      search.
AB  - The orientation-bias hypothesis states that there is a bias to attend to the
      right visual hemifield (RVF) when there is spatial competition between stimuli in
      the left and right hemifield [Pollmann, S. (1996). A pop-out induced extinction
      like phenomenon in neurologically intact subjects. Neuropsychologia, 34(5), 413
      425. doi: 10.1016/0028-3932(95)00125-5 ]. In support of this hypothesis, stronger
      interference was reported for RVF distractors with contralateral targets. In
      contrast, previous studies using rapid serial visual presentation (RSVP) found
      stronger interference from distractors in the left visual hemifield (LVF). We
      used the additional singleton paradigm to test whether this discrepancy was due
      to the different distractor features that were employed (colour vs. orientation).
      Interference from the colour distractor with contralateral targets was larger in
      the RVF than in the LVF. However, the asymmetrical interference disappeared when
      observers had to search for an inconspicuous colour target instead of the
      inconspicuous shape target. We suggest that the LVF orienting-bias is limited to
      situations where search is driven by bottom-up saliency (singleton search)
      instead of top-down search goals (feature search). In contrast, analysis of the
      literature suggests the opposite for the LVF bias in RSVP tasks. Thus, the
      attentional asymmetry may depend on whether the task involves temporal or spatial
      competition, and whether search is based on bottom-up or top-down signals.

PMID- 28502227
TI  - Malaria and severe anemia over eight years at Gambo Rural Hospital, southern
      Ethiopia.
AB  - Evolution of incident malaria and frequency of anemia were analyzed over eight
      years in a rural hospital in southern Ethiopia. Capillary blood samples were
      tested for hemoglobin concentration, and in some instances for malaria parasites,
      at Gambo Rural General Hospital between January 2007 and September 2014, and the
      results recorded. Main demographic data were also recorded in subjects with
      Plasmodium sp. infections. Of a total of 54,493 blood samples taken from 45,096
      different patients, 21,723 (39.9%) samples from 19,173 (42.5%) patients were
      tested for malaria parasites. Malaria was diagnosed in 825 (3.79%, 95% CI 3.55%,
      4.06%) instances (58.3% P. vivax and 41.7% P. falciparum; one episode in 575
      patients and two episodes in 125 patients). A sustained decrease in yearly
      incidence of malaria was observed between 2011 (6.1%) and 2014 (2.4%) (p < 0.01).
      Of all the malaria patients, those with hemoglobin levels less than 8 g/dL, were
      younger compared to those with levels of 8 g/dL or more (median age of 5 years
      vs. 18 years; p < 0.01) and more commonly infected with P. falciparum (57.1% vs.
      34.8%; p < 0.001). In multivariate analysis, severe anemia (hemoglobin <8 g/dL)
      in the context of anemia was associated with P falciparum infection (adjusted odd
      ratio [OR] 2.48, 95% confidence interval [CI] 1.68, 3.65) and younger age (OR
      1.06, 95% CI 1.04, 1.07).

PMID- 28502228
TI  - The toxic effects of polychlorinated biphenyl (Aroclor 1242) on Tm3 Leydig cells.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental
      contaminants that disrupt endocrine function in biological systems, especially in
      the male reproductive system. Previous studies on the reproductive toxicity of
      PCBs have focused on the impairment of spermatogenesis, disruption of
      steroidogenesis, decreased sperm number, and infertility. Aroclor 1242 is a
      commercial mixture with an average of 42% chlorine by weight. The purpose of the
      present study was to elucidate the hazardous effects of Aroclor 1242 on Leydig
      cells through an evaluation of cell viability, lipid peroxidation, hydroxyl
      radicals, H2O2 production, antioxidant enzymes, and steroidogenic enzymes. Leydig
      cells were exposed to Aroclor 1242 for 24 h under basal and luteinizing hormone
      stimulated conditions at different concentrations (ranging from 10-16 M to 10-6
      M). After incubation, Leydig cells were measured for cell viability, lipid
      peroxidation, reactive oxygen species (hydroxyl radical and H2O2), antioxidant
      enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione
      S-transferase), and steroidogenic enzymes (3beta-hydroxysteroid dehydrogenase
      [HSD] and 17beta-HSD). The results showed that cell viability was reduced only at
      Aroclor 1242 concentrations of 10-6 M and 10-8 M, whereas lipid peroxidation and
      reactive oxygen species increased relative to the concentration. Furthermore,
      antioxidant systems and steroidogenesis were interrupted to varying degrees,
      relative to the concentration. These findings suggest that exposure to Aroclor
      1242 at high concentrations may result in detrimental effects to Leydig cell
      homeostasis. In addition, Aroclor 1242 may impair steroidogenesis, especially
      testosterone biosynthesis, by inhibiting two important steroidogenic enzymes.

PMID- 28502230
TI  - The Emerging Genetic-Genomic Era and the Implications for the Holistic Nurse.

PMID- 28502229
TI  - Hexavalent chromium induces reactive oxygen species and impairs the antioxidant
      power of human erythrocytes and lymphocytes: Decreased metal reducing and free
      radical quenching ability of the cells.
AB  - The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to
      be closely associated with the generation of free radicals and reactive oxygen
      species. These species are produced when Cr(VI) is reduced to its trivalent form
      in the cell. This process results in oxidative stress due to an imbalance between
      the detoxifying ability of the cell and the production of free radicals. We have
      studied the effect of potassium dichromate (K2Cr2O7), a [Cr(VI)] compound, on the
      antioxidant power of human erythrocytes and lymphocytes under in vitro
      conditions. Incubation of erythrocytes and lymphocytes with different
      concentrations of K2Cr2O7 resulted in a marked dose-dependent decrease in reduced
      glutathione and an increase in oxidized glutathione and reactive oxygen species
      levels. The antioxidant power of the cells was decreased, as determined by metal
      reducing and free radical quenching assays. These results show that [Cr(VI)]
      upregulates the generation of reactive oxygen species and, as a consequence, the
      cellular antioxidant defences are compromised. The resulting oxidative stress may
      contribute to Cr(VI)-induced cellular damage.

PMID- 28502231
TI  - Examination of the Use of Healing Touch by Registered Nurses in the Acute Care
      Setting.

PMID- 28502232
TI  - Exploring the Global Applicability of Holistic Nursing.

PMID- 28502233
TI  - Introduction to Guest Editorials.

PMID- 28502234
TI  - A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced
      gonadal damage.
AB  - This study aimed to evaluate the protective effect of a gonadotropin-releasing
      hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model.
      Forty mice (female B6, 6-8 weeks old, weighing 16-18 g) were divided randomly
      into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose
      of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and
      4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2
      weeks before the administration of docetaxel. The ovaries were removed 6 weeks
      after docetaxel or saline injection. Total follicle number decreased in Group 3
      compared to Group 1. There was a significant difference between the Groups 3 and
      4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in
      Groups 1, 2, and 4; however, in Group 3, only a small number were stained and
      destruction of the ovarian structure was observed. There was no
      immunohistochemistry staining with gamma-H2AX in Groups 1, 2, and 4. However,
      gamma-H2AX staining of the primordial follicles was observed in Group 3. GnRH
      agonists may protect ovarian follicles from docetaxel-induced ovarian damage
      considering the total follicle number, follicle proliferation, and double-strand
      DNA breaks. Impact statement Protection of the ovarian reserve and prevention of
      infertility are the primary quality of life issues in young cancer patients. In
      this study, ovarian suppression by gonadotropin-releasing hormone agonists
      protected ovarian follicles from docetaxel-induced ovarian damage considering the
      total follicle number, follicle proliferation, and double-strand DNA break. The
      findings of our study will provide useful information for fertility preservation
      in women with cancer, undergoing chemotherapy with docetaxel.

PMID- 28502235
TI  - Molecular analysis and genetic diversity of Aedes albopictus (Diptera, Culicidae)
      from China.
AB  - Aedes albopictus is one of the most invasive species, which can carry Dengue
      virus, Yellow fever virus and more than twenty arboviruses. Based on
      mitochondrial gene cytochrome c oxidase I (COI) and samples collected from 17
      populations, we investigated the molecular character and genetic diversity of Ae.
      albopictus from China. Altogether, 25 haplotypes were detected, including 10
      shared haplotypes and 15 private haplotypes. H1 was the dominant haplotype, which
      is widely distributed in 13 populations. Tajima'D value of most populations was
      significantly negative, demonstrating that populations experienced rapid range
      expansion recently. Most haplotypes clustered together both in phylogenetic and
      median-joining network analysis without clear phylogeographic patterns. However,
      neutrality tests revealed shallow divergences among Hainan and Guangxi with other
      populations (0.15599 <= FST <= 0.75858), which probably due to interrupted gene
      flow, caused by geographical isolations. In conclusion, Ae. albopictus
      populations showed low genetic diversity in China.

PMID- 28502236
TI  - Family Presence in the Adult ICU During Bedside Procedures.
AB  - PURPOSE: To understand perspectives of family members of adult patients admitted
      to the medical-surgical intensive care unit (ICU) regarding their presence during
      procedures. METHODS: Respondents completed a questionnaire about procedures the
      patient had undergone, their desire to be present, and their experience.
      Procedures of interest were endotracheal intubation; chest compressions; vascular
      catheter insertion; and gastric, chest, and rectal tubes. Impact of Events Scale
      Revised (IES-R) was completed at the time of questionnaire completion and again 1
      month later to evaluate the psychological impact of witnessing a procedure.
      RESULTS: Ninety-seven respondents completed the questionnaire on behalf of 72
      patients. More than 90% patients had at least 1 procedure. Only 29 (30%) family
      members were present for at least 1 procedure, and 44% to 100% wished to be
      present. Of the 68 respondents not present for a procedure, 18 (26.5%) wanted to
      be present. The IES-R was completed by 52 (95%) of 55 respondents who witnessed
      any procedure at time 1 and 28 (51%) of 55 respondents at time 2; mean IES-R
      scores were 8.0 and 8.8 ( P = .68), respectively. Only 2 participants had IES-R
      >33, signifying the likely presence of posttraumatic stress disorder. CONCLUSION:
      Family members wish to be present for ICU procedures, and there are no adverse
      psychological effects.

PMID- 28502238
TI  - Parotid gland mean dose as a xerostomia predictor in low-dose domains.
AB  - PURPOSE: Xerostomia is a common side effect of radiotherapy resulting from
      excessive irradiation of salivary glands. Typically, xerostomia is modeled by the
      mean dose-response characteristic of parotid glands and prevented by mean dose
      constraints to either contralateral or both parotid glands. The aim of this study
      was to investigate whether normal tissue complication probability (NTCP) models
      based on the mean radiation dose to parotid glands are suitable for the
      prediction of xerostomia in a highly conformal low-dose regime of modern
      intensity-modulated radiotherapy (IMRT) techniques. MATERIAL AND METHODS: We
      present a retrospective analysis of 153 head and neck cancer patients treated
      with radiotherapy. The Lyman Kutcher Burman (LKB) model was used to evaluate
      predictive power of the parotid gland mean dose with respect to xerostomia at 6
      and 12 months after the treatment. The predictive performance of the model was
      evaluated by receiver operating characteristic (ROC) curves and precision-recall
      (PR) curves. RESULTS: Average mean doses to ipsilateral and contralateral parotid
      glands were 25.4 Gy and 18.7 Gy, respectively. QUANTEC constraints were met in
      74% of patients. Mild to severe (G1+) xerostomia prevalence at both 6 and 12
      months was 67%. Moderate to severe (G2+) xerostomia prevalence at 6 and 12 months
      was 20% and 15%, respectively. G1 + xerostomia was predicted reasonably well with
      area under the ROC curve ranging from 0.69 to 0.76. The LKB model failed to
      provide reliable G2 + xerostomia predictions at both time points. CONCLUSIONS:
      Reduction of the mean dose to parotid glands below QUANTEC guidelines resulted in
      low G2 + xerostomia rates. In this dose domain, the mean dose models predicted G1
      + xerostomia fairly well, however, failed to recognize patients at risk of G2 +
      xerostomia. There is a need for the development of more flexible models able to
      capture complexity of dose response in this dose regime.

PMID- 28502237
TI  - Investigation of the effective components of the flowers of Trollius chinensis
      from the perspectives of intestinal bacterial transformation and intestinal
      absorption.
AB  - CONTEXT: The flowers of Trollius chinensis Bunge (Ranunculaceae), used for
      respiratory tract infections, mainly contain flavonoids, phenolic acids, and
      alkaloids; however, the effective components are debatable because of their
      unclear in vivo activities. OBJECTIVE: This study investigates the effective
      components from the perspectives of biotransformation and absorption. MATERIALS
      AND METHODS: Both single person derived- and multiple people-derived intestinal
      florae were used to investigate the biotransformation of aqueous extract of the
      flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0
      mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2)
      monolayers and everted gut sacs were employed to evaluate the intestinal
      absorption of the intestinal bacterial transformed AEOF at the concentrations of
      10, 20, and 30 mg/mL, respectively, for 180 min. RESULTS: 2"-O-beta-l
      Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid,
      proglobeflowery acid, and trolline in AEOF were not transformed by intestinal
      bacteria, while isoquercetin and trollioside were completely transformed. The
      Papp values of 2"-O-beta-l-galactopyranosylorientin, orientin, and vitexin
      calculated based on the experimental data of intestinal absorption were at the
      levels of 10-5, whereas those of veratric acid, proglobeflowery acid, and
      trolline were at 10-4. The mass ratio of flavonoids to phenolic acids to
      alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. DISCUSSION
      AND CONCLUSION: The dominant position of flavonoids was replaced by phenolic
      acids after absorption. In addition to flavonoids which are usually considered as
      the dominant effective ones, phenolic acids and alkaloids should be also very
      important for the efficacy of these flowers.

PMID- 28502239
TI  - Data versus Spock: lay theories about whether emotion helps or hinders.
AB  - The android Data from Star Trek admired human emotion whereas Spock viewed
      emotion as irrational and maladaptive. The theory that emotions fulfil adaptive
      functions is widely accepted in academic psychology but little is known about
      laypeople's theories. The present study assessed the extent to which laypeople
      share Data's view of emotion as helpful or Spock's view of emotion as a
      hindrance. We also assessed how help and hinder theory endorsement were related
      to reasoning, emotion regulation, and well-being. Undergraduates (N = 630)
      completed a stressful timed reasoning task and questionnaires that assessed their
      theories of emotion, emotion regulation strategies, happiness, and social
      support. Overall, participants viewed emotion more as a help than a hindrance.
      The more they endorsed the view that emotion helps, the better their reasoning
      scores. Endorsing a help theory also predicted the use of reappraisal which, in
      turn, predicted greater happiness and social support. In contrast, endorsing the
      view that emotion hinders was associated with emotion suppression and less social
      support. Thus, people's theories about the functionality of emotion may have
      important implications for their reasoning and emotional well-being.

PMID- 28502240
TI  - Pediatric Primary Care Providers' Use of Behavioral Health Consultation.
AB  - This column describes a qualitative study in which 32 primary care providers
      (PCPs) reported barriers to and facilitators of using a behavioral health (BH)
      consultation program. Barriers included program incompatibility with
      organizational culture, limited exposure to the program, existing access to
      referral sources, and negative beliefs about BH consultation. Reported
      facilitators included having personal relationships with BH program staff,
      exposure to program information, and positive beliefs about BH consultation. PCPs
      recommended outreach activities and optimal program features to increase use of
      BH consultation.

PMID- 28502241
TI  - Competitive Employment Outcomes Among Veterans in VHA Therapeutic and Supported
      Employment Services Programs.
AB  - OBJECTIVE: The study assessed whether receiving specific types of Veterans Health
      Administration (VHA) Therapeutic and Supported Employment Services (TSES) between
      fiscal years (FYs) 2006 and 2010 (a time frame that encompasses the Great
      Recession) was associated with obtaining competitive employment among veterans
      with mental illnesses. METHODS: The sample included 38,199 veterans discharged
      from the VHA's TSES program in FY 2006 through FY 2010. On the basis of program
      monitoring forms completed by TSES clinicians and workload data, veterans were
      classified as having received one main type of employment service: supported
      employment (SE), transitional work in the community (TW-community), transitional
      work in a Department of Veterans Affairs medical center (TW-VA), incentive
      therapy or sheltered workshop (IT/SW), and no main type of employment service.
      RESULTS: Compared with veterans who received TW-VA, those who received SE (odds
      ratio [OR]=1.25) or TW-community (OR=1.24) were more likely to be competitively
      employed (p<.001), and veterans who received IT/SW were less likely (OR=.85)
      (p<.001). The predicted probabilities for obtaining competitive employment ranged
      from 27.2% (IT/SW) to 34.9% (SE). Odds of achieving competitive employment
      (ORs=.60-.97) were significantly lower during the years of the Great Recession
      (2007-2009) and in the subsequent year (2010), compared with the year prior
      (p<.001 to <.05). CONCLUSIONS: Although rates of competitive employment were
      modest across all types of services, community-based employment services were
      associated with higher odds of achieving competitive employment, compared with
      services based in a medical center. The Great Recession negatively affected the
      likelihood of achieving competitive employment, regardless of the employment
      service received.

PMID- 28502242
TI  - Clinical Decision Making and Mental Health Service Use Among Persons With Severe
      Mental Illness Across Europe.
AB  - OBJECTIVE: The study explored relationships between preferences for and
      experiences of clinical decision making (CDM) with service use among persons with
      severe mental illness. METHODS: Data from a prospective observational study in
      six European countries were examined. Associations of baseline staff-rated
      (N=213) and patient-rated (N=588) preferred and experienced decision making with
      service use were examined at baseline by using binomial regressions and at 12
      month follow-up by using multilevel models. RESULTS: A preference by patients and
      staff for active patient involvement in decision making, rather than shared or
      passive decision making, was associated with longer hospital admissions and
      higher costs at baseline and with increases in admissions over 12 months
      (p=.043). Low patient-rated satisfaction with an experienced clinical decision
      was also related to increased costs over the study period (p=.005). CONCLUSIONS:
      A preference for shared decision making may reduce health care costs by reducing
      inpatient admissions. Patient satisfaction with decisions was a predictor of
      costs, and clinicians should maximize patient satisfaction with CDM.

PMID- 28502244
TI  - Evaluating the Implementation of Integrated Mental Health Care: A Systematic
      Review to Guide the Development of Quality Measures.
AB  - OBJECTIVE: Although the effectiveness of integrated mental health care has been
      demonstrated, its implementation in real-world settings is highly variable, may
      not conform to evidence-based practice, and has rarely been evaluated. Quality
      indicators can guide improvements in integrated care implementation. However, the
      literature on indicators for this purpose is limited. This article reports
      findings from a systematic review of existing measures by which to evaluate
      integrated care models in primary care settings. METHODS: Bibliographic databases
      and gray literature sources, including academic conference proceedings, were
      searched to July 2014. Measures used or proposed to evaluate integrated care
      implementation or outcomes were extracted and critically appraised. A qualitative
      synthesis was conducted to generate a panel of unique measures and to group these
      measures into broad domains and specific dimensions of integrated care program
      performance. RESULTS: From 172 literature sources, 1,255 measures were extracted,
      which were distilled into 148 unique measures. Existing literature frequently
      reports integrated care program effectiveness vis-a-vis evidence-based care
      processes and individual clinical outcomes, as well as efficiency (cost
      effectiveness) and client satisfaction. No measures of safety of care and few
      measures of equitability, accessibility, or timeliness of care were located,
      despite the known benefits of integrated care in several of these areas.
      CONCLUSIONS: To realize the potential for quality measurement to improve
      integrated care implementation, future measures will need to incorporate domains
      of quality that are presently unaddressed; microprocesses of care that influence
      effectiveness, sustainability, and transferability of models of care; and client
      and health care provider perspectives on meaningful measures of quality.

PMID- 28502243
TI  - A 60-Week Prospective RCT of a Self-Management Intervention for Individuals With
      Serious Mental Illness and Diabetes Mellitus.
AB  - OBJECTIVES: A 60-week randomized controlled trial assessed the effects of
      targeted training in illness management (TTIM) versus treatment as usual among
      200 individuals with serious mental illness and diabetes mellitus. METHODS: The
      study used the Clinical Global Impression (CGI), the Montgomery-Asberg Depression
      Rating Scale (MADRS), and the Brief Psychiatric Rating Scale (BPRS) to assess
      psychiatric symptoms; the Global Assessment of Functioning (GAF) and the Sheehan
      Disability Scale (SDS) to assess functioning; the 36-Item Short-Form Health
      Survey (SF-36) to assess general health, and serum glycosylated hemoglobin
      (HbA1c) to assess diabetes control. RESULTS: Participants' mean+/-SD age was
      52.7+/-9.5 years, and 54% were African American. They were diagnosed as having
      depression (48%), schizophrenia (25%), and bipolar disorder (28%). At baseline,
      depression severity was substantial but psychosis severity was modest. At 60
      weeks, there was greater improvement among TTIM participants versus treatment-as
      usual recipients on the CGI (p<.001), the MADRS (p=.016), and the GAF (p=.003).
      Diabetes knowledge was significantly improved among TTIM participants but not in
      the treatment-as-usual group. In post hoc analyses among participants whose HbA1c
      levels at baseline met recommendations set by the American Diabetes Association
      for persons with high comorbidity (53%), TTIM participants had minimal change in
      HbA1c over the 60-week follow-up, whereas HbA1c levels worsened in the treatment
      as-usual group. CONCLUSIONS: TTIM was associated with improved psychiatric
      symptoms, functioning, and diabetes knowledge compared with treatment as usual.
      Among participants with better diabetes control at baseline, TTIM participants
      had better diabetes control at 60 weeks compared with recipients of treatment as
      usual.

PMID- 28502245
TI  - Involuntary Psychiatric Admissions and Development of Psychiatric Services as an
      Alternative to Full-Time Hospitalization in France.
AB  - OBJECTIVE: The development of alternatives to full-time hospitalization in
      psychiatry is limited because consensus about the benefits of such alternatives
      is lacking. This study assessed whether the development of such alternatives in
      French psychiatric sectors was associated with a reduction in involuntary
      inpatient care, taking into account other factors that are potentially associated
      with involuntary admission. METHODS: Data on whether a patient had at least one
      involuntary full-time admission in 2012 were extracted from the French national
      discharge database for psychiatric care. The development of alternatives to full
      time hospitalization was estimated as the percentage of human resources allocated
      to these alternatives out of all human resources allocated to psychiatry,
      measured at the level of the hospital hosting each sector. Other factors
      potentially associated with involuntary admission (characteristics of patients,
      health care providers, and the environment) were extracted from administrative
      databases, and a multilevel logistic model was carried out to account for the
      nested structure of the data. RESULTS: Significant variations were observed
      between psychiatric sectors in rates of involuntary inpatient admissions. A large
      portion of the variation was explained by characteristics of the sectors. A
      significant negative association was found between involuntary admissions and the
      development of alternatives to full-time hospitalization, after adjustment for
      other factors associated with involuntary admissions. CONCLUSIONS: Findings
      suggest that the development of alternatives to full-time hospitalization is
      beneficial for quality of care, given that it is negatively associated with
      involuntary full-time admissions. The reduction of such admissions aligns with
      international recommendations for psychiatric care.

PMID- 28502246
TI  - Time in Assertive Community Treatment: A Statewide Quality Improvement Initiative
      to Reduce Length of Participation.
AB  - The investigators describe a New York State initiative to increase flow through
      assertive community treatment (ACT) while encouraging transition to less
      intensive services. This initiative began as ACT approached full capacity and as
      evidence emerged that participants can sustain recovery post-ACT. Comparison of
      performance indicators over time showed that time in ACT decreased, turnover rate
      increased, and the percentage of ACT participants who met treatment objectives
      rose. Also, post-ACT rates of ambulatory behavioral health follow-up increased
      while rates of psychiatric inpatient hospitalization decreased. Monitoring
      utilization of services while demonstrating positive outcomes has become
      increasingly critical as states shift to managed health care.

PMID- 28502247
TI  - Assessing the Costs and Benefits of Insuring Psychological Services as Part of
      Medicare for Depression in Canada.
AB  - OBJECTIVE: The study estimated costs and effects associated with increasing
      access to publicly funded psychological services for depression in a public
      health care system. METHODS: Discrete event simulation modeled clinical events
      (relapse, recovery, hospitalizations, suicide attempts, and suicide), health
      service use, and cost outcomes over 40 years in a population with incident
      depression. Parameters included epidemiologic and economic data from the
      literature and data from a secondary analysis of the 2012 Canadian Community
      Health Survey on mental health. Societal costs were measured with the human
      capital approach. Analyses estimated the incremental cost-effectiveness ratio
      associated with improved access to psychological services among individuals not
      receiving adequate mental health care and reporting an unmet need for such care
      compared with present use of health services for mental health reasons. RESULTS:
      Over 40 years, increased access to mental health services in a simulated
      population of adults with incident depression would lead to significantly lower
      lifetime prevalence of hospitalizations (27.9% versus 30.2% base case) and
      suicide attempts (14.1% versus 14.6%); fewer suicides (184 versus 250); a per
      person gain of .17 quality-adjusted life years; and average societal cost savings
      of $2,590 CAD per person (range $1,266-$6,320). Publicly funding psychological
      services would translate to additional costs of $123,212,872 CAD ($67,709,860
      $190,922,732) over 40 years. Savings to society would reach, on average,
      $246,997,940 CAD ($120,733,356-$602,713,120). CONCLUSIONS: In Canada, every $1
      invested in covering psychological services would yield $2.00 ($1.78 to $3.15) in
      savings to society. Covering psychological services as part of Medicare for
      individuals with an unmet need for mental health care would pay for itself.

PMID- 28502248
TI  - How Do Private Health Plans Manage Specialty Behavioral Health Treatment Entry
      and Continuing Care?
AB  - OBJECTIVE: This study examined private health plans' arrangements for accessing
      and continuing specialty behavioral health treatment in 2010 as federal health
      reforms were being implemented. These management practices have historically been
      stricter in behavioral health care than in general medical care; however, the
      Mental Health Parity and Addiction Equity Act of 2010 required parity in
      management policies. METHODS: The data source was a nationally representative
      survey of private health plans' behavioral health treatment management approaches
      in 2010. Health plan executives were asked about activities for their plan's
      three products with highest enrollment (weighted N=8,427, 88% response rate).
      RESULTS: Prior authorization for outpatient behavioral health care was rarely
      required (4.7% of products), but 75% of products required authorization for
      ongoing care and over 90% required prior authorization for other levels of care.
      The most common medical necessity criteria were self-developed and American
      Society of Addiction Medicine criteria. Nearly all products had formal standards
      to limit waiting time for routine and urgent treatment, but almost 30% lacked
      such standards for detoxification services. A range of wait time-monitoring
      approaches was used. CONCLUSIONS: Health plans used a variety of methods to
      influence behavioral health treatment entry and continuing care. Few relied on
      prior authorization for outpatient care, but the use of other approaches to
      influence, manage, or facilitate access was common. Results provide a baseline
      for understanding the current management environment for specialty behavioral
      health care. Tracking health plans' approaches over time will be important to
      ensure that access to behavioral health care is not prohibitively restrictive.

PMID- 28502249
TI  - Psychiatric Mental Health Nursing Advanced Practice Workforce: Capacity to
      Address Shortages of Mental Health Professionals.
AB  - There is a recognized shortage of mental health professionals licensed to provide
      the full scope of mental health services, including assessment, diagnosis, and
      prescribing. Psychiatric mental health advanced practice nurses (PMH APNs) have
      the education and licensure to provide these services, address provider shortages
      and increase access to services. Unfortunately, federal reports and mental health
      workforce studies inaccurately depict important characteristics of PMH APNs,
      particularly their scope of practice, a situation that creates misunderstanding
      and impedes workforce planning. This Open Forum provides an accurate depiction of
      the PMH APN workforce, its size, scope of practice, and its capacity to increase
      access to mental health services. Also considered are the implications of using
      integrated care to increase access to mental health treatment. PMH APNs could
      increase the reach of these collaborative care models, which require constructing
      interprofessional teams in which each provider practices to the top of his or her
      license.

PMID- 28502250
TI  - Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in
      Plasmodium falciparum erythrocytic stages.
AB  - BACKGROUND: Malaria is a widespread infectious disease that threatens a large
      proportion of the population in tropical and subtropical areas. Given the
      emerging resistance against the current standard anti-malaria chemotherapeutics,
      the development of alternative drugs is urgently needed. New anti-malarials
      representing chemotypes unrelated to currently used drugs have an increased
      potential for displaying novel mechanisms of action and thus exhibit low risk of
      cross-resistance against established drugs. RESULTS: Phenotypic screening of a
      small library (32 kinase-inhibitor analogs) against Plasmodium falciparum NF54
      luc asexual erythrocytic stage parasites identified a diarylthioether
      structurally unrelated to registered drugs. Hit expansion led to a series in
      which the most potent congener displayed nanomolar antiparasitic activity (IC50 =
      39 nM, 3D7 strain). Structure-activity relationship analysis revealed a
      thieno[2,3-d]pyrimidine on one side of the thioether linkage as a prerequisite
      for antiplasmodial activity. Within the series, the oxazole derivative KuWei173
      showed high potency (IC50 = 75 nM; 3D7 strain), good solubility in aqueous
      solvents (1.33 mM), and >100-fold selectivity toward human cell lines. Rescue
      experiments identified inhibition of the plasmodial coenzyme A synthesis as a
      possible mode of action for this compound class. CONCLUSIONS: The class of
      antiplasmodial bishetarylthioethers reported here has been shown to interfere
      with plasmodial coenzyme A synthesis, a mechanism of action not yet exploited for
      registered anti-malarial drugs. The oxazole congener KuWei173 displays double
      digit nanomolar antiplasmodial activity, selectivity against human cell lines,
      high drug likeness, and thus represents a promising chemical starting point for
      further drug development.

PMID- 28502253
TI  - PRACTICE OF CONSANGUINITY AND ATTITUDES TOWARDS RISK IN THE PASHTUN POPULATION OF
      KHYBER PAKHTUNKHWA, PAKISTAN.
AB  - SummaryThis study aimed to investigate the frequency of consanguineous marriages
      and level of understanding of consanguinity-associated genetic risks in the
      Pashtun population, Pakistan. Information was gathered using a detailed
      questionnaire completed by 1500 individuals of both sexes over the 11-month
      period between April 2015 and February 2016. The mean inbreeding coefficient of
      the respondents was calculated and a five-point response scale was used to assess
      their understanding of consanguinity risks. The frequency of consanguineous
      marriages in the Pashtun population was found to be 58.3%, with a mean inbreeding
      coefficient of 0.0259. Marriage between second cousins was found to be the
      dominant marriage type. Level of education was found to be negatively related to
      the incidence of consanguineous marriage (p<0.001), and higher consanguinity was
      reported among the rural than the urban population (p<0.001). Participants in the
      >=25-year age group, those with a higher level of education and those residing in
      urban areas exhibited a significantly higher understanding of consanguinity
      risks. The overall prevalence of consanguinity in the Pashtun population is high,
      demonstrating the need for awareness of its risks in the target population. The
      timely dissemination of information on potential health-related risks and the
      introduction of genetic counselling in the region would benefit both the
      individuals concerned and the community in general.

PMID- 28502251
TI  - St John's wort (Hypericum perforatum)-induced psychosis: a case report.
AB  - BACKGROUND: St John's wort (Hypericum perforatum) has been known for centuries
      for its therapeutic properties and its efficacy as an antidepressant has been
      confirmed by a growing body of evidence. During the last two decades it has also
      come to prominence with a wider public, due to advertising efforts across Europe
      and United States of America. However, its availability without prescription, as
      an over-the-counter medication, raises some concern regarding its clinical
      management and unsupervised administration to individuals with psychopathological
      risks. To date, the evidence available regarding the administration of Hypericum
      in people with severe mental health problems is still meager and refers mainly to
      affective disorder spectrum or psychotic relapse in people with established
      diagnoses. To the best of our knowledge, this is the first report regarding the
      onset of psychotic features in a patient presenting with psychotic diathesis.
      CASE PRESENTATION: The case discussed in this report is a 25-year-old white man,
      not known to the psychiatric services, with a history of brief and self-remitting
      drug-induced psychosis and a positive family history of psychotic depression. He
      was admitted to hospital due to the onset of florid psychotic symptoms
      concomitant with self-administration of Hypericum perforatum. CONCLUSIONS: The
      aim of this report is to promote further systematic research, draw the attention
      of clinicians to the potential risks of Hypericum precipitating psychosis, and
      raise awareness among health professionals to investigate and caution their
      patients on the haphazard use of phytotherapeutics such as Hypericum.

PMID- 28502254
TI  - Dactylogyrids (Platyhelminthes, Monogenoidea) from the gills of Hoplias
      malabaricus (Characiformes: Erythrinidae) from coastal rivers of the Oriental
      Amazon Basin: species of Urocleidoides and Constrictoanchoratus n. gen.
AB  - Five species of Urocleidoides (one new) and two new species of
      Constrictoanchoratus n. gen. are described in this study. All were collected from
      the gills of Hoplias malabaricus (Characiformes: Erythrinidae) captured in six
      localities of coastal rivers of the north-eastern sector the State of Para
      (Oriental Amazon): Urocleidoides brasiliensis Rosim, Mendoza-Franco & Luque,
      2011; Urocleidoides bulbophallus n. sp.; Urocleidoides cuiabai Rosim, Mendoza
      Franco & Luque, 2011; Urocleidoides eremitus Kritsky, Thatcher & Boeger, 1986;
      Urocleidoides malabaricusi Rosim, Mendoza-Franco & Luque, 2011;
      Constrictoanchoratus lemmyi n. gen. n. sp.; and Constrictoanchoratus
      ptilonophallus n. gen. n. sp. This is the first reported occurrence of the four
      previously described species of Urocleidoides parasitizing H. malabaricus from
      streams in the Oriental Amazon Basin. The analysis of voucher specimens of U.
      eremitus parasitizing the gills of H. malabaricus from the Upper Parana River
      floodplain in the limits of States of Parana and Mato Grosso do Sul, Brazil,
      indicates that these specimens are members of a new species of Urocleidoides,
      described here as Urocleidoides paranae n. sp. Constrictoanchoratus n. gen. is
      proposed for the species with a male copulatory organ sclerotized, coiled,
      clockwise; ventral anchor with elongate superficial root, inconspicuous deep
      root; dorsal anchor with inconspicuous roots, and a constriction at the
      intersection between the shaft and the point. The host-parasite diversity
      scenario and host specificity of the species of Constrictoanchoratus n. gen. and
      Urocleidoides from the gills of H. malabaricus are also discussed in this study.

PMID- 28502252
TI  - Differential analysis of mutations in the Jewish population and their
      implications for diseases.
AB  - Sequencing large cohorts of ethnically homogeneous individuals yields genetic
      insights with implications for the entire population rather than a single
      individual. In order to evaluate the genetic basis of certain diseases
      encountered at high frequency in the Ashkenazi Jewish population (AJP), as well
      as to improve variant annotation among the AJP, we examined the entire exome,
      focusing on specific genes with known clinical implications in 128 Ashkenazi Jews
      and compared these data to other non-Jewish populations (European, African, South
      Asian and East Asian). We targeted American College of Medical Genetics
      incidental finding recommended genes and the Catalogue of Somatic Mutations in
      Cancer (COSMIC) germline cancer-related genes. We identified previously known
      disease-causing variants and discovered potentially deleterious variants in known
      disease-causing genes that are population specific or substantially more
      prevalent in the AJP, such as in the ATP and HGFAC genes associated with
      colorectal cancer and pancreatic cancer, respectively. Additionally, we tested
      the advantage of utilizing the database of the AJP when assigning pathogenicity
      to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew
      early-onset breast cancer (BC) patients. Importantly, population-based filtering
      using our AJP database enabled a reduction in the number of potential causal
      variants in the BC cohort by 36%. Taken together, population-specific sequencing
      of the AJP offers valuable, clinically applicable information and improves AJP
      filter annotation.

PMID- 28502255
TI  - A moist edge environment aids the regeneration of traumatic tympanic membrane
      perforations.
AB  - OBJECTIVE: To review the history of moist therapy used to regenerate traumatic
      tympanic membrane perforations. STUDY DESIGN: Literature review. METHODS: The
      literature on topical agents used to treat traumatic tympanic membrane
      perforations was reviewed, and the advantages and disadvantages of moist therapy
      were analysed. RESULTS: A total of 76 studies were included in the analysis.
      Topical applications of certain agents (e.g. growth factors, Ofloxacin Otic
      Solution, and insulin solutions) to the moist edges of traumatic tympanic
      membrane perforations shortened closure times and improved closure rates.
      CONCLUSION: Dry tympanic membrane perforation edges may be associated with crust
      formation and centrifugal migration, delaying perforation closure. On the
      contrary, moist edges inhibit necrosis at the perforation margins, stimulate
      proliferation of granulation tissue and aid eardrum healing. Thus, moist
      perforation margins upon topical application of solutions of appropriate agents
      aid the regeneration of traumatic tympanic membrane perforations.

PMID- 28502256
TI  - Survival outcomes following salvage surgery for oropharyngeal squamous cell
      carcinoma: systematic review.
AB  - BACKGROUND: Recurrent oropharyngeal squamous cell carcinoma causes great
      morbidity and mortality. This systematic review analyses survival outcomes
      following salvage surgery for recurrent oropharyngeal squamous cell carcinoma.
      METHODS: A comprehensive search of various electronic databases was conducted.
      Studies included patients with recurrent or residual oropharyngeal squamous cell
      carcinoma treated with salvage surgery. Primary outcomes were survival rates
      following salvage surgery. Secondary outcomes included time to recurrence,
      staging at time of recurrence, post-operative complications, and factors
      associated with mortality and recurrence. Methodological appraisal and data
      extraction were conducted as per Joanna Briggs Institute methodology. RESULTS:
      Eighteen articles were included. The two- and five-year survival rates of the
      patients were 52 per cent and 30 per cent respectively. CONCLUSION: Improvements
      in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were
      associated with improvements in two-year overall survival rates, with minimal
      change to five-year overall survival rates. Various factors were identified as
      being associated with long-term overall survival, thus assisting clinicians in
      patient counselling and selection for salvage surgery.

PMID- 28502257
TI  - Physics moves to the provinces: the Siberian physics community and Soviet power,
      1917-1940.
AB  - The rich tradition of Siberian science and higher education is little known
      outside Russian academic circles. Using institutional history, this article
      focuses on the founding and pre-war period of the Siberian Physical Technical
      Institute, the establishment of its research focus and its first difficult steps
      to become a leading centre of R & D in Siberia. Based on archival materials, the
      article describes how local and national physicists justified the institute's
      creation by demonstrating ties with industry and building on the presence of a
      cohort of locally trained physicists, whose numbers were augmented by Leningrad
      specialists. The strength of local cadres enabled the institute to navigate civil
      war and cultural revolution successfully. Physicists were able to take advantage
      of ongoing industrialization campaigns to gain support to create the institute,
      although local disputes and economic problems slowed its further development. The
      article describes the circulation of scientific, political and philosophical
      knowledge between Moscow, Leningrad and the provinces, and the impact of
      Bolshevik rule and Stalinism on the Siberian physics enterprise.

PMID- 28502258
TI  - Balloon Eustachian tuboplasty treatment of longstanding Eustachian tube
      dysfunction.
AB  - BACKGROUND: Eustachian tube dysfunction is a poorly defined condition associated
      with various symptoms and it can predispose to middle-ear disease. Balloon
      dilation Eustachian tuboplasty has been proposed as a treatment for Eustachian
      tube dysfunction. OBJECTIVE: To evaluate the subjective and objective outcomes of
      balloon dilation Eustachian tuboplasty in patients with recurrent, previously
      treated chronic Eustachian tube dysfunction. METHODS: The study was conducted on
      11 patients (13 ears) who had undergone previous unsuccessful medical and
      surgical treatment. Tympanometry was the primary outcome measure. Secondary
      outcome measures included pure tone audiogram assessment and seven-item
      Eustachian Tube Dysfunction Questionnaire score. RESULTS: Balloon dilation
      Eustachian tuboplasty resulted in significant improvements in 11 patients'
      subjective but not objective outcome measures. CONCLUSION: The objective
      abnormality and subjective symptoms in Eustachian tube dysfunction may represent
      two distinct pathological processes, which may nevertheless influence and
      exacerbate each other.

PMID- 28502259
TI  - Effects of goldfish (Carassius auratus) population size and body condition on the
      transmission of Gyrodactylus kobayashii (Monogenea).
AB  - Field surveys indicate that host population size, rather than density, is the
      most important determinant of monogenean infection dynamics. To verify this
      prediction, epidemic parameters were monitored for 70 days at five host
      population sizes held at constant density using a goldfish - Gyrodactylus
      kobayashii laboratory model. During the first 20 days, the rate of increase of
      prevalence and mean abundance was faster in small host populations. Total mean
      prevalence and total mean abundance throughout the experiment were not
      significantly affected by host population sizes. Higher transmission rates were
      detected in larger host populations. However, there were no significant
      differences in effective contact rates among the five host populations on each
      sampling day during the first 20 days, implying that contact rates may be
      saturated at a sufficiently high host density. These results demonstrate that the
      epidemic occurs more quickly in smaller host populations at the beginning of the
      experiment. However, the epidemic is independent of the host population size due
      to the similar effective contact rates in the five population sizes. Significant
      negative influence of the initial body condition (Kn) of uninfected goldfish on
      total mean abundance of parasites suggests that susceptibility of hosts is also a
      determinant of parasite transmission.

PMID- 28502260
TI  - The first study on opportunistic intestinal microsporidiosis in IBD patients
      receiving immunosuppressive medications in Iran.
AB  - Microsporida are known as opportunistic unicellular organisms and have recently
      been reclassified as fungi that have been frequently reported from patients with
      congenital and acquired immunity failure disorders, worldwide. However, use of
      immunosuppressive medications in inflammatory bowel disease (IBD) patients
      significantly decreases overall immunity, and increases their susceptibility to
      opportunistic infections. Totally, 71 stool samples were collected from IBD
      patients consisted of 69 ulcerative colitis (UC) patients and two Crohn's disease
      (CD) patients. All patients had taken immunosuppressive and/or immunomodulator
      drugs for at least 3 weeks. DNA was extracted from all stool samples and Nested
      PCR was performed using genus-specific primers based on small subunit ribosomal
      RNA (SSU rRNA) gene. Fisher's Exact Test was applied to evaluate statistical
      association between microsporidia infection and sex, age and types of IBD. Mean
      of age +/- s.d., women and men percentage of the attended patients were 36.17 +/-
      11.93, 60.6%, and 39.4%, respectively. A 440-bp fragment of SSU rRNA gene
      attributed to Enterocytozoon bieneusi was amplified from 12.7% of IBD patients.
      No Encephalitozoon DNA was detected in the samples. No microsporidia-positive
      sample was found in CD patients. Fisher's Exact Test showed that there was no
      statistically significant correlation between intestinal microsporidiosis and
      age, sex, and IBD types with P values: 0.389, 1.00, and 1.00, respectively. This
      study has shown IBD patients undergoing immunosuppressive/immunomodulators
      medications, which may be susceptible to intestinal microsporida infection. E.
      bieneusi is the commonest intestinal microsporidan reported from IBD patients.

PMID- 28502261
TI  - Profiles of Executive Function Across Children with Distinct Brain Disorders:
      Traumatic Brain Injury, Stroke, and Brain Tumor.
AB  - OBJECTIVES: This study examined whether children with distinct brain disorders
      show different profiles of strengths and weaknesses in executive functions, and
      differ from children without brain disorder. METHODS: Participants were children
      with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke
      (N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a
      corresponding matched comparison group consisting of children with orthopedic
      injury (N=61), asthma (N=15), and classmates without medical illness (N=68),
      respectively. Shifting, inhibition, and working memory were assessed,
      respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch)
      subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison
      groups did not differ in TEA-Ch performance and were merged into a single control
      group. Profile analysis was used to examine group differences in TEA-Ch subtest
      scaled scores after controlling for maternal education and age. RESULTS: As a
      whole, children with brain disorder performed more poorly than controls on
      measures of executive function. Relative to controls, the three brain injury
      groups showed significantly different profiles of executive functions.
      Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed
      among the brain disorder groups. CONCLUSIONS: Results suggest that different
      childhood brain disorders result in distinct patterns of executive function
      deficits that differ from children without brain disorder. Implications for
      clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).

PMID- 28502263
TI  - Infection, specificity and host manipulation of Australapatemon sp. (Trematoda,
      Strigeidae) in two sympatric species of leeches (Hirudinea).
AB  - Factors that drive parasite specificity and differences in infection dynamics
      among alternative host species are important for ecology and evolution of host
      parasite interactions, but still often poorly known in natural systems. Here, we
      investigated spatiotemporal dynamics of infection, host susceptibility and
      parasite-induced changes in host phenotype in a rarely explored host-parasite
      system, the Australapatemon sp. trematode infecting two sympatric species of
      freshwater leeches, Erpobdella octoculata and Helobdella stagnalis. We show
      significant variation in infection abundance between the host species in both
      space and time. Using experimental infections, we also show that most of this
      variation likely comes from interspecific differences in exposure rather than
      susceptibility. Moreover, we demonstrate that the hiding behaviour of E.
      octoculata, but not that of H. stagnalis, was impaired by the infection
      irrespective of the parasite abundance. This may increase susceptibility of E.
      octoculata to predation by the final avian host. We conclude that differences in
      patterns of infection and in behavioural alterations among alternative sympatric
      host species may arise in narrow spatial scales, which emphasises the importance
      of local infection and transmission dynamics for parasite life cycles.

PMID- 28502262
TI  - Effects of combined IUGR and prenatal stress on the development of the
      hippocampus in a fetal guinea pig model.
AB  - Intrauterine growth restriction (IUGR) and maternal stress during pregnancy are
      two compromises that negatively impact neurodevelopment and increase the risk of
      developing later life neuropsychiatric disorders such as schizophrenia,
      depression and behavioural disorders. Neurosteroids, particularly
      allopregnanolone, are important in protecting the developing brain and promoting
      many essential neurodevelopmental processes. Individually, IUGR and prenatal
      stress (PS) reduce myelination and neurogenesis within affected fetal brains,
      however less information is available on the combined effects of these two
      disorders on the term fetal brain. This study aimed to investigate how IUGR and
      PS impairs the neurosteroid pathway when combined using a guinea pig model, and
      how these then disrupt the neurodevelopment of the fetus. Uterine artery blood
      flow restriction was performed at GA30-35 to induce growth restriction, whilst PS
      was induced by exposure of the dam to a strobe light during gestation commencing
      GA40 and repeated every 5 days. Exposure in this model caused reductions in
      hippocampal CA1 MBP immunostaining of male fetuses in both IUGR alone and IUGR+PS
      paradigms but only by IUGR in the subcortical white mater, compared with control
      males. Plasma allopregnanolone was reduced by both stressors irrespective of sex,
      whereas GFAP or MAP2 expression were not affected by either stressor. Female
      neurodevelopment, as assessed by these markers, was unimpeded by these
      compromises. The addition of prenatal stress did not further compound these
      deficits.

PMID- 28502264
TI  - Study of the impact on Salmonella of moving outdoor pigs to fresh land.
AB  - Anecdotal evidence has suggested that outdoor-kept pigs show an improvement to
      health and productivity after being moved to a new site. This study explores
      whether Salmonella occurrence reduced and was sustained after moving to a new
      site. Nine farms were followed for a year in which four sampling visits were
      completed. The highest detection of Salmonella was from pooled faecal dropping
      from pigs, run-off/ pooled water, rodents and wild birds. Descriptive summaries
      showed that the prevalence of both all Salmonella and serovars of public health
      importance were lower at all visits after the move. Some variability was shown in
      results from individual farms, but a year after the move, six farms still
      maintained a lower prevalence. A risk factor model showed that the prevalence at
      visits 2 and 3 after the move was significantly lower than baseline, after
      accounting for a number of significant factors that were included in the model.
      These were sample type and seasonality (included as a priori), presence of
      coughing in the sampled group and Glasser's disease on the farm, and the use of
      tent or kennel accommodation. This finding provides important evidence that more
      frequent site moves may help reduce Salmonella prevalence in outdoor herds.

PMID- 28502265
TI  - Psychological autopsy study comparing suicide decedents, suicide ideators, and
      propensity score matched controls: results from the study to assess risk and
      resilience in service members (Army STARRS).
AB  - BACKGROUND: The suicide rate has increased significantly among US Army soldiers
      over the past decade. Here we report the first results from a large psychological
      autopsy study using two control groups designed to reveal risk factors for
      suicide death among soldiers beyond known sociodemographic factors and the
      presence of suicide ideation. METHODS: Informants were next-of-kin and Army
      supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched
      on known sociodemographic risk factors for suicide and Army history variables,
      and 118 control soldiers who reported suicide ideation in the past year. RESULTS:
      Results revealed that most (79.3%) soldiers who died by suicide have a prior
      mental disorder; mental disorders in the prior 30-days were especially strong
      risk factors for suicide death. Approximately half of suicide decedents tell
      someone that they are considering suicide. Virtually all of the risk factors
      identified in this study differed between suicide cases and propensity-score
      matched controls, but did not significantly differ between suicide cases and
      suicide ideators. The most striking difference between suicides and ideators was
      the presence in the former of an internalizing disorder (especially depression)
      and multi-morbidity (i.e. 3+ disorders) in the past 30 days. CONCLUSIONS: Most
      soldiers who die by suicide have identifiable mental disorders shortly before
      their death and tell others about their suicidal thinking, suggesting that there
      are opportunities for prevention and intervention. However, few risk factors
      distinguish between suicide ideators and decedents, pointing to an important
      direction for future research.

PMID- 28502267
TI  - Within-host interference competition can prevent invasion of rare parasites.
AB  - Competition between parasite species or genotypes can play an important role in
      the establishment of parasites in new host populations. Here, we investigate a
      mechanism by which a rare parasite is unable to establish itself in a host
      population if a common resident parasite is already present (a 'priority
      effect'). We develop a simple epidemiological model and show that a rare parasite
      genotype is unable to invade if coinfecting parasite genotypes inhibit each
      other's transmission more than expected from simple resource partitioning. This
      is because a rare parasite is more likely to be in multiply-infected hosts than
      the common genotype, and hence more likely to pay the cost of reduced
      transmission. Experiments competing interfering clones of bacteriophage infecting
      a bacterium support the model prediction that the clones are unable to invade
      each other from rare. We briefly discuss the implications of these results for
      host-parasite ecology and (co)evolution.

PMID- 28502266
TI  - Refining the Frommelt Attitude Toward the Care of the Dying Scale (FATCOD-B) for
      medical students: A confirmatory factor analysis and Rasch validation study.
AB  - OBJECTIVE: Given the increasing number of patients requiring palliative care and
      the need for more professionals who are able to provide care for the dying
      comfortably, assessment of medical attitudes toward end-of-life care is becoming
      a key aspect of medical education. The present study aimed to establish whether
      the Frommelt Attitude Toward the Care Of the Dying, Form B (FATCOD-B) meets
      current psychometric standards of validity for an assessment tool in medical
      education. METHOD: The participants were 200 undergraduate medical students.
      Since in a previous study the FATCOD-B was found to have a weak structure due to
      poor item validity, a refined version was proposed and tested in the present
      study. Confirmatory factor analysis and the Rasch model were employed to assess
      its dimensionality and psychometric properties. RESULTS: The construct measured
      by the FATCOD-B continues to be misspecified. The tool has a two-dimensional
      structure. The first is well-structured and demonstrates appreciable measurement
      and discriminant capabilities. The second has low validity because its
      measurement capabilities are based on weakly correlated items. SIGNIFICANCE OF
      RESULTS: Our results suggest that the FATCOD-B measures a two-dimensional
      construct and that only its first dimension is a robust measurement tool for use
      in medical education to evaluate undergraduates' attitudes about caring for the
      dying.

PMID- 28502268
TI  - Comparison of two-dimensional and three-dimensional echocardiographic strain in
      children with CHD.
AB  - BACKGROUND: In CHD, three-dimensional strain analysis may overcome limitations of
      Doppler and two-dimensional strain of the left ventricle. The aims of this study
      were to evaluate feasibility and reproducibility of three-dimensional
      longitudinal, circumferential, and radial systolic strain by three-dimensional
      speckle-tracking echocardiography compared with two-dimensional echocardiography.
      METHODS: Patients with CHD, biventricular circulation with a systemic left
      ventricle, and who had two- and three-dimensional imaging performed on the same
      day from 2010 to 2014 were included. Quantitative two- and three-dimensional
      strain analyses were performed (two-dimensional cardiac performance analysis
      version 1.2 and four-dimensional left ventricular analysis version 3.1). Intra-
      and inter-observer variabilities were calculated on 25 studies. RESULTS: A total
      of 30 patients, including 19 (61%) males, with a median age of 3.6 years (0.1-22
      years) were included. The mean fractional shortening was 34.6+/-5.3%, and the
      mean ejection fraction was 62.0+/-6.4%. Measurement of two- and three-dimensional
      strain was feasible in >95% of segments. Good correlation was observed between
      longitudinal and circumferential strain (r=0.92, p?0.001 and r=0.87, p?0.001),
      but not radial strain (r=0.29, p=0.2). Intra- and inter-observer agreements were
      better for three-dimensional compared with two-dimensional strain, and better for
      both two- and three-dimensional longitudinal and circumferential strains compared
      with radial strain. CONCLUSION: Left ventricular three-dimensional strain
      analysis is feasible in children with CHD. The reproducibility of longitudinal
      and circumferential strain by three-dimensional analyses is better. Further
      longitudinal studies are warranted for the potential clinical application of this
      new technology.

PMID- 28502269
TI  - PENEPMA: A Monte Carlo Program for the Simulation of X-Ray Emission in Electron
      Probe Microanalysis.
AB  - The Monte Carlo program PENEPMA performs simulations of X-ray emission from
      samples bombarded with both electron and photon beams. It is based on the general
      purpose Monte Carlo simulation package PENELOPE, an elaborate system for the
      simulation of coupled electron-photon transport in arbitrary materials, and on
      the geometry subroutine package PENGEOM, which tracks particles through complex
      material structures defined by quadric surfaces. After a brief description of the
      interaction models implemented in the simulation subroutines and of the structure
      and operation of PENEPMA, we provide an overview of the capabilities of the
      program along with several examples of its application to the modeling of
      electron probe microanalysis measurements.

PMID- 28502270
TI  - Insecure attachment predicts depression and death anxiety in advanced cancer
      patients.
AB  - : ABSTRACTObjective:The prevalence of depression as well as adjustment and
      anxiety disorders is high in advanced cancer patients, and research exploring
      intraindividual factors leading to high psychological distress is
      underrepresented. Cancer patients' feelings about security and trust in their
      healthcare providers have a significant influence on how they deal with their
      disease. The perception of social support is affected by patients' attachment
      styles and influences their reactions to feelings of dependency and loss of
      control. We therefore aimed to explore attachment and its association with
      psychological distress in patients with advanced cancer. METHOD: We obtained data
      from the baseline measurements of a randomized controlled trial in advanced
      cancer patients. Patients were sampled from the university medical centers of
      Hamburg and Leipzig, Germany. The main outcome measures included the Patient
      Health Questionnaire, the Death and Dying Distress Scale, the Memorial Symptom
      Assessment Scale, and the Experience in Close Relationships Scale for assessing
      attachment insecurity. RESULTS: A total of 162 patients were included. We found
      that 64% of patients were insecurely attached (fearful-avoidant 31%, dismissing
      17%, and preoccupied 16%). A dismissing attachment style was associated with more
      physical symptoms but did not predict psychological distress. A fearful-avoidant
      attachment style significantly predicted higher death anxiety and depression,
      whereas preoccupied attachment predicted higher death anxiety only. Overall,
      insecure attachment contributed to the prediction of depression (10%) and death
      anxiety (14%). SIGNIFICANCE OF RESULTS: The concept of attachment plays a
      relevant role in advanced cancer patients' mental health. Healthcare providers
      can benefit from knowledge of advanced cancer patients' attachment styles and how
      they relate to specific mental distress. Developing a better understanding of
      patients' reactions to feelings of dependency and distressing emotions can help
      us to develop individually tailored advanced cancer care programs and
      psychotherapeutic interventions.

PMID- 28502271
TI  - QUALITY OF SAMPLE SIZE ESTIMATION IN TRIALS OF MEDICAL DEVICES: HIGH-RISK DEVICES
      FOR NEUROLOGICAL CONDITIONS AS EXAMPLE.
AB  - BACKGROUND: The aim of this study was to assess the quality of reporting sample
      size calculation and underlying design assumptions in pivotal trials of high-risk
      medical devices (MDs) for neurological conditions. METHODS: Systematic review of
      research protocols for publicly registered randomized controlled trials (RCTs).
      In the absence of a published protocol, principal investigators were contacted
      for additional data. To be included, trials had to investigate a high-risk MD,
      registered between 2005 and 2015, with indications stroke, headache disorders,
      and epilepsy as case samples within central nervous system diseases. Extraction
      of key methodological parameters for sample size calculation was performed
      independently and peer-reviewed. RESULTS: In a final sample of seventy-one
      eligible trials, we collected data from thirty-one trials. Eighteen protocols
      were obtained from the public domain or principal investigators. Data
      availability decreased during the extraction process, with almost all data
      available for stroke-related trials. Of the thirty-one trials with sample size
      information available, twenty-six reported a predefined calculation and
      underlying assumptions. Justification was given in twenty and evidence for
      parameter estimation in sixteen trials. Estimates were most often based on
      previous research, including RCTs and observational data. Observational data were
      predominantly represented by retrospective designs. Other references for
      parameter estimation indicated a lower level of evidence. CONCLUSIONS: Our
      systematic review of trials on high-risk MDs confirms previous research, which
      has documented deficiencies regarding data availability and a lack of reporting
      on sample size calculation. More effort is needed to ensure both relevant
      sources, that is, original research protocols, to be publicly available and
      reporting requirements to be standardized.

PMID- 28502272
TI  - Adverse childhood experiences, exposure to a natural disaster and posttraumatic
      stress disorder among survivors of the 2011 Great East Japan earthquake and
      tsunami.
AB  - AIMS: To investigate whether adverse childhood experiences (ACEs) modify the
      impact of exposure to a natural disaster (the 2011 Great East Japan earthquake
      and tsunami) on the occurrence of posttraumatic stress disorder (PTSD) among
      older people. METHODS: Data were collected as part of the Japan Gerontological
      Evaluation Study (JAGES), which is an on-going epidemiological survey
      investigating social determinants of health among older people across Japan.
      Information on PTSD symptoms based on the Screening Questionnaire for Disaster
      Mental Health, traumatic exposure to the earthquake (i.e., house damage and loss
      of relatives/friends during the earthquake/tsunami) and ACEs was obtained from
      580 participants aged 65 or older living in Iwanuma City, Miyagi Prefecture,
      which suffered severe damage as a result of the earthquake and the subsequent
      tsunami in March 2011. Associations were examined using Poisson regression
      analysis with a robust variance estimator after adjusting for covariates.
      RESULTS: The prevalence of PTSD was 9.7% in this population; compared to those
      with no traumatic experience, the prevalence of PTSD was approximately two times
      higher among those who experienced the loss of close friends/relatives (PR =
      1.84, 95% CI = 1.11-3.03, p = 0.018), or whose house was damaged (PR = 2.15, 95%
      CI = 1.07-4.34, p = 0.032). ACE was not significantly associated with PTSD.
      Stratified analyses by the presence of ACE showed that damage due to the
      earthquake/tsunami was associated with PTSD only among those without ACEs; more
      specifically, among non-ACE respondents the PR of PTSD associated with house
      damage was 6.67 (95% CI = 1.66-26.80), while for the loss of a relative or a
      close friend it was 3.56 (95% CI = 1.18-10.75). In contrast, no statistically
      significant associations were observed among those with ACEs. CONCLUSION:
      Following the Great East Japan earthquake/tsunami in 2011 a higher risk of
      developing PTSD symptoms was observed in 2013 especially among older individuals
      without ACEs. This suggests that ACEs might affect how individuals respond to
      subsequent traumatic events later in life.

PMID- 28502273
TI  - Modiolar ossification in paediatric patients with auditory neuropathy.
AB  - OBJECTIVE: To describe our finding of increased ossification of the modiolus in
      paediatric patients with auditory neuropathy who met criteria for cochlear
      implantation. METHODS: A retrospective case series with a comparison group at a
      tertiary referral centre is described. Seven paediatric patients with auditory
      neuropathy who met criteria for and underwent cochlear implantation were
      identified. Fifteen paediatric implantees with bilateral profound sensorineural
      hearing loss were included as the comparison group. All patients underwent pre
      operative computed tomography. Attenuation at the modiolus was measured in all
      subjects by a neuroradiologist blinded to clinical information. RESULTS:
      Attenuation values in the modiolus in the auditory neuropathy patients (mean +/-
      standard deviation = 796.2 +/- 53.0 HU) was statistically significantly higher
      than in the comparison sensorineural hearing loss patients (267.1 +/- 45.6 HU; p
      < 0.05, t-test). CONCLUSION: Patients with auditory neuropathy who meet criteria
      for cochlear implantation demonstrate significantly higher modiolar attenuation
      on computed tomography imaging, consistent with increased ossification at the
      modiolus.

PMID- 28502274
TI  - Superior petrosal sinus causing superior canal dehiscence syndrome.
AB  - OBJECTIVE: To determine signs and symptoms for superior canal dehiscence syndrome
      caused by the superior petrosal sinus. METHODS: A review of the English-language
      literature on PubMed and Embase databases was conducted, in addition to a multi
      centre case series report. RESULTS: The most common symptoms of 17 patients with
      superior petrosal sinus related superior canal dehiscence syndrome were: hearing
      loss (53 per cent), aural fullness (47 per cent), pulsatile tinnitus (41 per
      cent) and pressure-induced vertigo (41 per cent). The diagnosis was made by
      demonstration of the characteristic bony groove of the superior petrosal sinus
      and the 'cookie bite' out of the superior semicircular canal on computed
      tomography imaging. CONCLUSION: Pulsatile tinnitus, hearing loss, aural fullness
      and pressure-induced vertigo are the most common symptoms in superior petrosal
      sinus related superior canal dehiscence syndrome. Compared to superior canal
      dehiscence syndrome caused by the more common apical location of the dehiscence,
      pulsatile tinnitus and exercise-induced vertigo are more frequent, while sound
      induced vertigo and autophony are less frequent. There is, however, considerable
      overlap between the two subtypes. The distinction cannot as yet be made on
      clinical signs and symptoms alone, and requires careful analysis of computed
      tomography imaging.

PMID- 28502275
TI  - Use of acellular dermal matrices in laryngotracheal and pharyngeal
      reconstruction: systematic review.
AB  - BACKGROUND: Acellular dermal matrices are increasingly used in laryngotracheal
      and pharyngeal reconstruction, but specific indications and the type of acellular
      dermal matrix used vary. The authors systematically reviewed outcomes relating to
      acellular dermal matrix use in head and neck reconstruction. METHODS: Electronic
      databases were searched through 1 May 2016 for literature on acellular dermal
      matrix use in laryngotracheal and pharyngeal reconstruction. Studies were
      appraised for surgical indications, outcomes and study design. RESULTS: Eleven
      publications with 170 cases were included. Eight articles reported on acellular
      dermal matrix use in oncological reconstruction. Most studies were case series;
      no high-level evidence studies were identified. Graft extrusion was more common
      in non-oncological applications. In general, post-oncological reconstruction with
      an acellular dermal matrix demonstrated complication rates similar to those
      reported without an acellular dermal matrix. CONCLUSION: Evidence in support of
      acellular dermal matrix use in head and neck reconstruction is generally poor.
      Prospective comparative studies are required to define the indications, safety
      and effectiveness of acellular dermal matrices in laryngotracheal and pharyngeal
      reconstruction.

PMID- 28502276
TI  - Characterization of tabanid flies (Diptera: Tabanidae) in South Africa and Zambia
      and detection of protozoan parasites they are harbouring.
AB  - Tabanids are haematophagous flies feeding on livestock and wildlife. In the
      absence of information on the relationship of tabanid flies and protozoan
      parasites in South Africa and Zambia, the current study was aimed at
      characterizing tabanid flies collected in these two countries as well as
      detecting protozoan parasites they are harbouring. A total of 527 tabanid flies
      were collected whereby 70.2% were from South Africa and 29.8% were from Zambia.
      Morphological analysis revealed a total of five different genera collected from
      the sampled areas namely: Ancala, Atylotus, Haematopota, Philoliche and Tabanus.
      DNA extracted from South African Tabanus par and Tabanus taeniola tested positive
      for the presence of Trypanosoma congolense (Savannah) and Trypanosoma theileri
      whilst one member from T. par was positive for Trypanosoma brucei species. DNA
      extracted from Zambian tabanid flies tested positive for the presence of
      Besnoitia species at 1.27% (2/157), Babesia bigemina 5.73% (9/157), Theileria
      parva 30.11% (30/157) and 9.82% (14/157) for Trypanosoma evansi. This study is
      the first to report on relationship of Babesia and Theileria parasites with
      tabanid flies. Further investigations are required to determine the role of
      tabanids in transmission of the detected protozoan parasites in livestock and
      wildlife in South Africa and Zambia.

PMID- 28502277
TI  - Lactobacillus paracasei GMNL-32, Lactobacillus reuteri GMNL-89 and L. reuteri
      GMNL-263 ameliorate hepatic injuries in lupus-prone mice.
AB  - Probiotics are known to regulate host immunity by interacting with systemic and
      mucosal immune cells as well as intestinal epithelial cells. Supplementation with
      certain probiotics has been reported to be effective against various disorders,
      including immune-related diseases. However, little is known about the
      effectiveness of Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri
      GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263) in the management of
      autoimmune diseases, especially systemic lupus erythematosus (SLE). NZB/W F1
      mice, which are a lupus-prone animal model, were orally gavaged with GMNL-32,
      GMNL-89 or GMNL-263 to investigate the effects of these Lactobacillus strains on
      liver injuries in NZB/W F1 mice. The results thus obtained reveal that
      supplementary GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice ameliorates hepatic
      apoptosis and inflammatory indicators, such as matrix metalloproteinase-9
      activity and C-reactive protein and inducible nitric oxide synthase expressions.
      In addition, supplementation with GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice
      reduced the expressions of hepatic IL-1beta, IL-6 and TNF-alpha proteins by
      suppressing the mitogen-activated protein kinase and NF-kappaB signalling
      pathways. These findings, presented here for the first time, reveal that GMNL-32,
      GMNL-89 and GMNL-263 mitigate hepatic inflammation and apoptosis in lupus-prone
      mice and may support an alternative remedy for liver disorders in cases of SLE.

PMID- 28502278
TI  - A NEW HEALTH TECHNOLOGY ASSESSMENT SYSTEM FOR DEVICES: THE FIRST FIVE YEARS.
AB  - OBJECTIVES: The aim of this study was to review 5 years of activity from a new
      system devised by the National Institute for Health and Care Excellence (NICE),
      for assessing medical devices and diagnostics aimed at identifying and speeding
      adoption of technologies with clinical and cost advantages, compared with current
      practice in the United Kingdom healthcare system. METHODS: All eligible notified
      technologies were classified using the Food and Drug Administration and Global
      Medical Device Nomenclature nomenclatures. Decisions about selecting technologies
      for full assessment to produce NICE recommendations were reviewed, along with the
      reasons given to companies for not selecting products. RESULTS: Between 2009 and
      2014, 186 technologies were notified (46 percent therapeutic and 54 percent
      diagnostic). Thirty-nine were judged ineligible (no regulatory approval), and 147
      were considered by an independent committee. Of these, eighty (54 percent) were
      not selected for full assessment, most commonly because of insufficient evidence
      (86 percent): there were uncertainties specifically about benefits to the health
      service (54 percent), to patients (39 percent), and about cost (24 percent). The
      remaining 67 were selected and assessed for Medical Technology guidance (52
      percent) (noninferior and/or lower cost consequences than current practice), for
      Diagnostics guidance (43 percent) or other NICE recommendations about adoption
      and use. Classifying technologies by two different systems showed no selection
      bias for any technology type or disease area. CONCLUSIONS: Identifying new or
      under-used devices and diagnostics with potential benefits and promoting their
      adoption is important to health services in the United Kingdom and worldwide.
      This new system offers a means of fostering both uptake and further research.
      Lack of research data on new products is a major obstacle to evaluation.

PMID- 28502279
TI  - Evidence and molecular characterization of Bartonella spp. and hemoplasmas in
      neotropical bats in Brazil.
AB  - The order Chiroptera is considered the second largest group of mammals in the
      world, hosting important zoonotic virus and bacteria. Bartonella and hemotropic
      mycoplasmas are bacteria that parasite different mammals' species, including
      humans, causing different clinical manifestations. The present work aimed
      investigating the occurrence and assessing the phylogenetic positioning of
      Bartonella spp. and Mycoplasma spp. in neotropical bats sampled from Brazil.
      Between December 2015 and April 2016, 325 blood and/or tissues samples were
      collected from 162 bats comprising 19 different species sampled in five states of
      Brazil. Out of 322 bat samples collected, while 17 (5.28%) were positive to
      quantitative PCR for Bartonella spp. based on nuoG gene, 45 samples (13.97%) were
      positive to cPCR assays for hemoplasmas based on 16S rRNA gene. While seven
      sequences were obtained for Bartonella (nuoG) (n = 3), gltA (n = 2), rpoB (n =
      1), ftsZ (n = 1), five 16S rRNA sequences were obtained for hemoplasmas. In the
      phylogenetic analysis, the Bartonella sequences clustered with Bartonella
      genotypes detected in bats sampled in Latin America countries. All five
      hemoplasmas sequences clustered together as a monophyletic group by Maximum
      Likelihood and Bayesian Inference analyses. The present work showed the first
      evidence of circulation of Bartonella spp. and hemoplasmas among bats in Brazil.

PMID- 28502280
TI  - A Feedback-Controlled Mandibular Positioner Identifies Individuals With Sleep
      Apnea Who Will Respond to Oral Appliance Therapy.
AB  - STUDY OBJECTIVES: Mandibular protruding oral appliances represent a potentially
      important therapy for obstructive sleep apnea (OSA). However, their clinical
      utility is limited by a less-than-ideal efficacy rate and uncertainty regarding
      an efficacious mandibular position, pointing to the need for a tool to assist in
      delivery of the therapy. The current study assesses the ability to prospectively
      identify therapeutic responders and determine an efficacious mandibular position.
      METHODS: Individuals (n = 202) with OSA participated in a blinded, 2-part
      investigation. A system for identifying therapeutic responders was developed in
      part 1 (n = 149); the predictive accuracy of this system was prospectively
      evaluated on a new population in part 2 (n = 53). Each participant underwent a 2
      night, in-home feedback-controlled mandibular positioner (FCMP) test, followed by
      treatment with a custom oral appliance and an outcome study with the oral
      appliance in place. A machine learning classification system was trained to
      predict therapeutic outcome on data obtained from FCMP studies on part 1
      participants. The accuracy of this trained system was then evaluated on part 2
      participants by examining the agreement between prospectively predicted outcome
      and observed outcome. A predicted efficacious mandibular position was derived
      from each FCMP study. RESULTS: Predictive accuracy was as follows: sensitivity
      85%; specificity 93%; positive predictive value 97%; and negative predictive
      value 72%. Of participants correctly predicted to respond to therapy, the
      predicted mandibular protrusive position proved efficacious in 86% of cases.
      CONCLUSIONS: An unattended, in-home FCMP test prospectively identifies
      individuals with OSA who will respond to oral appliance therapy and provides an
      efficacious mandibular position. CLINICAL TRIAL REGISTRATION: The trial that this
      study reports on is registered on www.clinicaltrials.gov, ID NCT03011762, study
      name: Feasibility and Predictive Accuracy of an In-Home Computer Controlled
      Mandibular Positioner in Identifying Favourable Candidates for Oral Appliance
      Therapy.

PMID- 28502281
TI  - Self-Reported Sleep Duration and Self-Rated Health in Young Adults.
AB  - STUDY OBJECTIVES: This study aimed to determine the associations between the self
      reported sleep duration and self-rated health in young adults. METHODS: In this
      cross-sectional study, participants were 689 young adults (mean age 20 +/- 1.35
      years, 49.8% female). Sleep duration and self-rated health, as the main outcome
      of interest, were measured as self-reported. As potential covariates, we included
      sex, age, smoking status, alcohol consumption, physical activity, sedentary
      behavior, psychological distress, and body mass index. RESULTS: Approximately 30%
      of participants slept 7-8 hours, 17.4% were short sleepers (categories < 6 hours
      and 6-7 hours), and 53.9% were long sleepers (categories 8-10 hours and > 10
      hours of sleep). In an unadjusted model, compared with the reference category (7
      8 hours of sleep), those who slept < 6 hours (odds ratio 0.20; 95% confidence
      interval 0.08 to 0.48) and between 6-7 hours (odds ratio 0.43; 95% confidence
      interval 0.26 to 0.69) were less likely to have good self-rated health. In an
      adjusted model, short (< 7 hours) and long sleep (> 10 hours) were both
      associated with poor self-rated health. CONCLUSIONS: Our results suggest that
      both short (< 7 hours) and long (> 10 hours) sleepers have lower odds of having
      good self-rated health after adjusting for potential covariates. Health
      professionals should pay more attention to young adults, who have both short and
      long period of sleep, in order to prevent health problems and potential acute or
      chronic diseases.

PMID- 28502283
TI  - Why Should We Care About Selenium in Obstructive Sleep Apnea?

PMID- 28502282
TI  - Morning Diastolic Blood Pressure May Be Independently Associated With Severity of
      Obstructive Sleep Apnea in Non-Hypertensive Patients: A Cross-Sectional Study.
AB  - STUDY OBJECTIVES: The aim of the study is to verify a possible association
      between arterial blood pressure and obstructive sleep apnea (OSA) severity in a
      group of non-hypertensive patients. METHODS: This is a retrospective study of
      1,171 consecutive patients referred to the sleep laboratory with complaints
      suggestive of OSA who underwent standard diagnostic polysomnography. In total,
      454 patients with no History of arterial hypertension nor had received any such
      treatment were selected from this group. RESULTS: Patients with severe OSA (apnea
      hypopnea index [AHI] >= 30 events/h) presented with higher diastolic blood
      pressure (DBP) in the morning than healthy subjects (AHI < 5 events/h) or those
      suffering from mild (15 < AHI >= 5 events/h) or moderate OSA (30 < AHI >= 15
      events/h): 86.2 +/- 11.3 versus 79.2 +/- 8.5, 80.3 +/- 10.2 and 81.4 +/- 9.6
      mmHg, P < .01, respectively. In a linear regression model, a rise in morning DBP
      was predicted by AHI (beta = 0.14, P < .001) and body mass index (BMI) (beta =
      0.22, P < .01), but not by age (beta = 0.01, P = .92), male sex (beta = -0.06, P
      = .19), or smoking (beta = 0.01, P = .86). In contrast, no association existed
      between morning systolic blood pressure (SBP) and AHI independently of BMI, sex,
      age, or smoking. High blood pressure (ie, SBP >= 140 mmHg or DBP >= 90 mmHg on
      each of three measurements on different occasions) was predicted by age of 42
      years or older, BMI of at least 29 kg/m2, and severe OSA. CONCLUSIONS: High AHI,
      independent of obesity, age and sex, was associated with elevated DBP in the
      morning. Thus, elevated morning DBP may be one of the symptoms related to OSA
      that warrants specific diagnostics. COMMENTARY: A commentary on this article
      appears in this issue on page 861.

PMID- 28502284
TI  - Should Hyperarousal and Sleep Fragmentation Be Additional Treatment Targets When
      Treating OSA in PTSD With CPAP?

PMID- 28502285
TI  - The Continued Search for Optimal Therapy in Patients With OSA and PTSD.

PMID- 28502286
TI  - Do Obese Children Require Inpatient Monitoring After Adenotonsillectomy?

PMID- 28502287
TI  - The Need for a Reliable Sleep EEG Biomarker.

PMID- 28502288
TI  - Portable Sleep Monitoring Systems: Broadening the Horizons.

PMID- 28502289
TI  - Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton
      alteration.
AB  - Although doxorubicin (Dox)-induced oxidative stress is known to be associated
      with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not
      only generates free radicals, but also affects actin cytoskeleton stability. We
      showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations,
      resulting in central stress fiber disruption at early time points and cell
      periphery cortical actin formation at a later stage, in HeLa cells.
      Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was
      initially evoked by Dox-induced RhoA signaling, resulting in a rapid
      phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In
      addition, a novel interaction between CIN and 14-3-3zeta was detected in the
      absence of Dox treatment. We demonstrated that CIN activity is quite contrary to
      14-3-3zeta binding, and the interaction leads to enhanced phosphorylated cofilin
      levels. Therefore, initial CIN activation regulation could be critical in Dox
      induced actin cytoskeleton remodeling through RhoA/cofilin signaling. [BMB
      Reports 2017; 50(6): 335-340].

PMID- 28502291
TI  - [ABIN1 is not involved in imatinib upregulating A20 to inhibit the activation of
      NF-kappaB pathway in Jurkat T cells].
AB  - Objective To investigate the effect of imatinib (IM) on the expressions of A20
      binding inhibitor of NF-kappaB1 (ABIN1) and A20 in Jurkat T cells. Methods Jurkat
      T cells were treated with 25, 50 and 100 nmol/L IM for 24 hours. The mRNA and
      protein levels of ABIN1, A20 and NF-kappaB were detected by real-time
      quantitative PCR and Western blotting. Results IM significantly inhibited both
      mRNA and protein levels of ABIN1 and NF-kappaB, but raised the mRNA and protein
      levels of A20; while phorbol 12-myristate 13-acetate/ionomycin increased the
      expression levels of ABIN1 and A20 mRNA and protein. Conclusion IM could
      upregulate A20 protein to inhibit the activation of NF-kappaB pathway in Jurkat T
      cells, which was independent of the ABIN1 protein.

PMID- 28502290
TI  - Deubiquitinase YOD1: the potent activator of YAP in hepatomegaly and liver
      cancer.
AB  - Advances in the understanding of the Hippo signaling as a key regulatory pathway
      of proliferation and apoptosis have provided mechanical insights for controlling
      organ size and tumorigenicity. Recently, much attention has been directed to the
      regulation of LATS1/2 (large tumor suppressor) kinases that phosphorylate
      YAP/TAZ, a transcriptional co-activator in the Hippo pathway, and control the
      level and nuclear localization of YAP/TAZ. In our recent work, we showed that
      deubiquitinase YOD1 stabilizes ITCH, and facilitates ITCH-mediated LATS1/2
      ubiquitination and degradation, resulting in increased YAP/TAZ level.
      Furthermore, we found that the YOD1- ITCH-LATS1/2-YAP/TAZ signaling axis is
      controlled by the differential expression of miR-21 in a cell-density-dependent
      manner. Using a transgenic mouse model, we showed that the inducible expression
      of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a
      YAP/TAZ-activitydependent manner. Moreover, a strong correlation was observed
      between YOD1 and YAP expression in liver cancer patients. Overall, our data
      suggest that YOD1 is a novel regulator of the Hippo pathway, and thereby a
      potential therapeutic target for liver cancer. [BMB Reports 2017; 50(6): 281
      282].

PMID- 28502292
TI  - [Autophagy modulates the levels of inflammatory cytokines in macrophages induced
      by lipopolysaccharide].
AB  - Objective To analyze the effect of autophagy on inflammatory response in
      macrophages induced by lipopolysaccharide (LPS) and investigate its molecular
      mechanism. Methods Bone marrow mesenchymal stem cells, which were separated from
      the femora of mice, were cultured and induced to differentiate into primary
      macrophages in vitro. The inflammatory cell model was established by stimulating
      the primary macrophages with LPS. Autophagy was inhibited by 3-methyladenine (3
      MA) or promoted by rapamycin. Green fluorescent protein-microtubule associated
      protein 1 light chain 3 (GFP-LC3) plasmid was used to transfect primary
      macrophages and the percentage of cells with GFP-LC3 puncta were counted in the
      different groups. The mRNA levels of LC3B, tumor necrosis factor alpha (TNF
      alpha), interleukin 1beta (IL-1beta), IL-6 and IL-12p40 were detected by real
      time quantitative PCR, and the protein levels of LC3B, nuclear factor kappaB (NF
      kappaB) and IkappaBalpha were determined by Western blotting. Results LC3B mRNA
      and protein expression levels were gradually up-regulated and the autophagosomes
      increased in the macrophages 2, 4 and 6 hours after treated by LPS. Compared with
      only LPS treatment group, autophagy inhibition by 3-MA pretreatment promoted the
      mRNA expressions of inflammatory cytokines including TNF-alpha, IL-1beta, IL-6
      and IL-12p40, and the autophagy induction by rapamycin pretreatment suppressed
      TNF-alpha, IL-1beta, IL-6 and IL-12p40. Meanwhile, 3-MA or rapamycin pretreatment
      further regulated the protein expressions of IkappaBalpha and p-NF-kBp65 induced
      by LPS in macrophages. Conclusion Autophagy can suppress the LPS-induced
      inflammatory response in macrophages by regulating NF-kappaB signaling pathway.

PMID- 28502293
TI  - [Wuwei Wentong Chubi Capsule promotes the autophagy in synovial tissue of
      adjuvant-induced arthritis rats and its mechanism].
AB  - Objective To evaluate the effect of Wuwei Wentong Chubi (WWWTCB) Capsule on the
      PI3K/AKT/mTOR signaling pathway in the synovial tissues of adjuvant-induced
      arthritis (AA) rats, and investigate its potential pharmacological mechanisms of
      treating rheumatoid arthritis. Methods Sixty Sprague Dawley (SD) rats were
      randomly assigned into six groups evenly: normal group, model group, WWWTCB
      groups at 0.80, 1.60, 3.20 g/kg body mass, and tripterygium glycosides tablet
      (TPT) group at 40 mg/kg body mass. Except for the normal group, the other five
      groups were induced into AA models with Complete Freund's Adjuvant (CFA). The
      WWWTCB or TPT, was administrated from day 12 after injection of CFA by gavage,
      once a day for 12 days. After that, unaffected ankle-joint tissues from the AA
      rats were collected for histopathological examination. The mRNA levels of PI3K,
      AKT, mTOR, p70s6 and beclin1 in the synovial tissue were detected by real-time
      quantitative PCR. Meanwhile, the protein levels of PI3K, AKT, p-AKT, mTOR, p
      mTOR, p70s6, p-p70s6 and beclin1 were determined by immunofluorescence
      histochemical staining and/or Western blotting. Results Compared with the model
      group, WWWTCB (1.60, 3.20 g/kg body mass) groups showed less ankle-joint injury
      and decreased proliferation of synovial cells in the ankle-joint tissues. In
      addition, the administration of WWWTCB decreased the mRNA and protein levels of
      PI3K, AKT, p-AKT, mTOR, p-mTOR, p70s6 and p-p70s6, while increased the level of
      beclin1. Conclusion WWWTCB ameliorated AA in rats. The improvement might be
      closely related to the inhibitory effect of WWWTCB on the PI3K/AKT/mTOR signaling
      pathway and its promoting effect on the autophagy activity of synovial cells.

PMID- 28502294
TI  - [Resiquimod (R848) has more stronger immune adjuvantivity than other tested TLR
      agonists].
AB  - Objective To compare and characterize the Th1 immune responses induced by the
      most commonly used commercial Toll-like receptor (TLR) agonists through in vivo
      and ex vivo experiments. Methods The concentrations of IL-12 were tested by ELISA
      after mouse dendritic cells (DCs) in vitro were stimulated by one of tested TLR
      agonists, including poly(I:C), monophosphoryl lipid A (MPLA), resiquimod (R848),
      cytosine polyguanine-C (CpG-C). The changes in percentage and phenotype of DCs,
      NK cells and effector T cells in the draining lymph nodes were analyzed by flow
      cytometry after BALB/c mice were immunized with ovalbumin (OVA) mixed with
      selected TLR agonist. The serum concentrations of specific anti-OVA IgG2a in the
      immunized mice were determined by ELISA. Results Only CpG-C and R848 could
      significantly induce the production of IL-12 from bone marrow-derived DCs in
      vitro. Among the tested TLR agonists, R848 was the most effective adjuvant in
      recruiting DCs and NK cells into lymph nodes, inducing the proliferation of CD4+
      and CD8+ effector T cells and the production of specific anti-OVA IgG2a in vivo.
      Conclusion R848 was the most potential Th1-promoting adjuvant among the tested
      TLR agonists.

PMID- 28502295
TI  - [Lactobacillus rhamnosus GG improves symptoms and its mechnism in mice with
      ovalbumin-induced food allergy].
AB  - Objective To investigate the effect of Lactobacillus rhamnosus GG (LGG) on
      peripheral blood IL-4/IFN-gamma in mice with ovalbumin-induced food allergy.
      Methods The mice with food allergy were divided into 3 groups (n=10 in each
      group): food allergy model group, low-dose LGG group (1*108 CFU/mL, 200 MUL/d)
      and high-dose LGG group (1*109 CFU/mL, 200 MUL/d). The healthy mice (n=10) served
      as a control group. Mice in the LGG groups were given LGG for consecutive 22 days
      after modeling. The control mice and the food allergy model mice were given
      normal saline instead of LGG. At day 23, the allergic score, body mass, thymus
      index, spleen index were recorded and calculated; the expressions of IgE, IL-4
      and IFN-gamma in peripheral blood were detected by ELISA; the pathological
      changes of small intestines were observed by HE staining and fecal flora were
      examined by bacterial culture. Results The thymus and spleen indexes had no
      significant differences within the 4 groups. Compared with the control group, IL
      4, allergic score, E.coli and bacteroides increased, and IFN-gamma, IFN-gamma/IL
      4, IgE, body mass, Bifidobacterium and Lactobacillus decreased in the mice with
      food allergy. Compared with the mice with food allergy, IL-4, allergic score,
      E.coli and Bacteroides decreased significantly, and IFN-gamma, IFN-gamma/IL-4,
      IgE, body mass, Bifidobacterium and Lactobacillus significantly increased in the
      LGG groups in a dose-dependent manner. In the food allergy model group, some
      edematous and necrotic epithelial cells were found in intestinal mucosa. Compared
      with the food allergy model group, the intestinal mucosa was integrated and the
      intestinal cells appeared ordered in the LGG groups. Conclusion LGG can
      remarkably improve the symptoms of ovalbumin-induced food allergy probably by
      decreasing IL-4/IFN-gamma ratio.

PMID- 28502296
TI  - [Recombinant Legionella pneumophila flagella protein A (rflaA) induces the
      secretion of IL-6 and IL-1beta in RAW264.7 cells in vitro].
AB  - Objective To investigate the effect of recombinant Legionella pneumophila
      flagella protein A (rflaA) on the secretion of interleukin-6 (IL-6) and
      interleukin-1beta (IL-1beta) by RAW264.7 macrophage and the possible mechanism.
      Methods RAW264.7 cells were treated with 0.000, 0.125, 0.250, 0.500, 1.000,
      2.000, 4.000 and 8.000 MUg/mL rflaA to determine the EC50 of rflaA using CCK-8
      assay. Secretion of IL-6 and IL-1beta were measured by ELISA at 24, 36 and 48
      hours after treatment of the cells with 0.04, 0.08 and 0.16 MUg/mL rflaA. At 6,
      12, 24, 36 and 48 hours after treatment of the cells with 0.04, 0.08 and 0.16
      MUg/mL rflaA, the expressions of IL-6, IL-1beta, NOD-like receptor protein 3
      (NLRP3) and caspase-1 mRNAs were detected by quantitative real-time PCR, and the
      expressions of NLRP3 and caspase-1 proteins were tested by Western blotting.
      Results RflaA enhanced the expressions of IL-6 and IL-1beta, and the higher
      concentration of rflaA was more potential. The expressions of IL-6 and IL-1beta
      reached peak when the cells were treated with 0.16 MUg/mL rflaA for 36 hours.
      Treatment of RAW264.7 cells with rflaA promoted the expressions of IL-6 and IL
      1beta, NLRP3 and caspase-1 mRNA, and 0.16 MUg/mL rflaA was the most potential at
      12 hours after treatment. Expressions of NLRP3 and caspase-1 protein increased
      after treatment with rflaA, and 0.16 MUg/mL rflaA induced the highest expression
      of both proteins at 24 hours after treatment. Conclusion RflaA could enhance the
      secretion of IL-6 and IL-1beta by promoting the expressions of NLRP3 and caspase
      1 in RAW264.7 cells.

PMID- 28502297
TI  - [Knock-down of cadherin 17 inhibits proliferation and promote apoptosis in
      noscapine-resistant human SW480 colon cancer cells].
AB  - Objective To investigate the effects of cadherin 17 (CDH17) on the proliferation
      and apoptosis of noscapine-resistant human SW480 colon cancer cells. Methods The
      level of CDH17 in noscapine-resistant human SW480 colon cancer cells was knocked
      down by small interfering RNA (siRNA), and the silence was confirmed by Western
      blotting and real-time quantitative PCR. Transfected SW480 cells were treated
      with noscapine, and then the proliferation and cell viability of SW480 cells were
      measured by MTT assay and plate clone formation assay, respectively; the
      apoptosis of SW480 cells was detected by flow cytometry combined with annexinV
      FITC/PI staining; the expressions of poly-ADP-ribose polymerase (PARP) and
      caspase-3 were determined by Western blotting. Results Compared with NC-siRNA
      group and control group, the expression levels of CDH17 protein and mRNA were
      down-regulated in the CDH17-siRNA-transfected SW480 cell lines. After noscapine
      treatment, compared with NC-siRNA and control group, the colony-forming ratio and
      cell viability were significantly lower in CDH17-siRNA -transfected cell lines,
      and the expression levels of cleaved-PARP and cleaved- caspase-3 were up
      regulated in CDH17-siRNA group, and the cell apoptosis rate increased. Conclusion
      Knock-down of CDH17 in SW480 cells can effectively inhibit cell proliferation and
      promote cell apoptosis as well as improve SW480 cell sensitivity to narcotine.

PMID- 28502298
TI  - [Forkhead domain inhibitor-6 (FDI-6) increases apoptosis and inhibits invasion
      and migration of laryngeal carcinoma cells by down-regulating nuclear FoxM1].
AB  - Objective To study the effects of new small molecular inhibitor, forkhead domain
      inhibitor-6 (FDI-6), on proliferation, apoptosis, invasion and migration in human
      laryngeal carcinoma Hep-2 cell line and the related mechanism. Methods MTT assay
      was used to test the proliferation rate of Hep-2 cells before and 12, 24 hours
      after treated with (5, 10, 20, 40, 80) MUmol/L of FDI-6. Flow cytometry (FCM) and
      TranswellTM chamber assay were respectively carried out to detect the apoptosis
      rate, cell invasion and migration in Hep-2 cells after treated by 10, 20 MUmol/L
      FDI-6 for 24 hours. Real-time quantitative PCR (qRT-PCR) and Western blotting
      were performed to determine the mRNA and protein levels of FoxM1, Bcl-2 and BAX,
      respectively. Results Cell proliferation rate was inhibited by FDI-6 in a dose-
      and time-dependent manner. Twenty-four hours after 10, 20 MUmol/L FDI-6
      treatment, the apoptosis rate in Hep-2 cells was elevated and the ability of cell
      invasion and migration was inhibited in a dose-dependent manner. The qRT-PCR
      showed that there was no significant change in FoxM1 mRNA expression with or
      without FDI-6 treatment. Western blotting showed that the total protein level of
      FoxM1 was not obviously changed, but Bcl-2 was down-regulated, BAX was up
      regulated. However, in the nuclear FoxM1 protein level decreased along with the
      ascent of FDI-6 concentration. Conclusion FDI-6 could induce cell apoptosis and
      inhibit cell proliferation, invasion and migration in Hep-2 cells. This may be
      related to the down-regulation of FoxM1 in the nucleus.

PMID- 28502299
TI  - [Tumor-associated macrophages promote the proliferation and migration as well as
      invasion of sorafenib-resistant hepatocellular carcinoma cells].
AB  - Objective To investigate the roles of tumor-associated macrophages (TAMs) and
      epithelial growth factor receptor (EGFR)/beta-catenin signaling pathway in
      sorafenib resistance of hepatocellular carcinoma cells. Methods Macrophages were
      isolated from peripheral blood mononuclear cells (PBMCs) and cultured in the
      presence of colony-stimulating factor (M-CSF) to obtain TAMs. Phenotypes of TAMs
      were identified. The level of epithelial growth factor (EGF) secreted by TAMs was
      detected by ELISA. CCK-8 assay was performed to verify the effects of EGF on
      HepG2 and SMMC7721 cell proliferation. TranswellTM assay was used to examine the
      effects of EGF on the invasion and migration ability of HepG2 and SMMC7721 cells.
      TAMs and hepatocellular carcinoma cells were co-cultured to study the downstream
      signaling pathways. Sorafenib-resistant HepG2 and SMMC7721 strains (R-HepG2 and R
      SMMC7721 cells) were prepared and then subjected to Western blotting and
      immunohistochemistry to examine the expression levels of beta-catenin and EGFR.
      Results TAMs we prepared were confirmed. Compared with HepG2 and SMMC7721 cells,
      R-HepG2 and R-SMMC7721 showed enhanced proliferation, invasion and migration
      abilities. The growth rates of sorafenib-resistant cell lines after co-cultured
      with TAMs were significantly higher than those of the controls. The protein
      expressions of beta-catenin and EGFR in sorafenib-resistant cells and
      hepatocellular carcinoma tissues were higher than those in the controls.
      Conclusion TAMs and EGFR/beta-catenin signaling pathway promote the
      proliferation, invasion and migration of sorafenib resistance of hepatocellular
      carcinoma cells.

PMID- 28502300
TI  - [Down-regulation of sphingosine kinase 1 (SphK1) enhances the chemosensitivity to
      cisplatin in human colon cancer RKO cells].
AB  - Objective To investigate the effect of sphingosine kinase 1 (SphK1) gene silence
      on the sensitivity to cisplatin (DDP) in RKO colon cancer cell line and the
      potential mechanism. Methods Targeted SphK1 gene lentivirus virus was constructed
      to infect RKO cells. The relative mRNA expression of SphK1 was detected by
      quantitative real-time PCR (qRT-PCR) and the protein level of SphK1 was
      determined by Western blotting. Then RKO cells were divided into three groups:
      down-regulated SphK1 group (shSphK1 group), negative control group (shControl
      group) and blank control group (control group). Cells of these groups were
      incubated for 0, 24, 48 and 72 hours with 0, 2, 4, 8, 16, 32 MUg/mL DDP. After
      treatment, cell viability was evaluated by MTT assay. Cell apoptosis index was
      determined by TUNEL. The expressions of ki67, Bcl-2, caspase-9 and caspase-3 were
      tested by Western blotting. Results Down-regulation of SphK1 inhibited cell
      proliferation and enhanced apoptosis of RKO cells, expecially after exposed to
      DDP. Silence of SphK1 sensitized RKO cells to DDP in a concentration- and time
      dependent manner. Cell proliferation of shSphK1 group was obviously reduced
      compared with control group or shControl group, and cell apoptosis rate of
      shSphK1 group significantly increased compared with control group or shControl
      group. Moreover, with the down-regulation of SphK1, the expressions of ki67 and
      Bcl-2 were depressed; the expressions of caspase-9 and caspase-3 were raised,
      especially after treated with DDP. Conclusion Down-regulation of SphK1 may
      decrease the expression of Bcl-2, increase the expressions of caspase-9 and
      caspase-3, inhibit cell proliferation, and promote cell apoptosis, thus improving
      chemosensitivity of colon cancer RKO cells to DDP.

PMID- 28502301
TI  - [Psychological distress promotes proliferation and invasion of glioma by
      upregulating lactate deoxygenase A].
AB  - Objective To investigate the role of lactate deoxygenase A (LDHA) expression in
      the proliferation and invasion of glioma promoted by the psychological distress.
      Methods The glioma-bearing nude mice were divided into tumor bearing group,
      stress tumor bearing group, negative control, short hairpin RNA (shRNA)-lactate
      dehydrogenase A (LDHA) group and shRNA-LDHA stress group. Four weeks after
      stress, the tumor size of each group was measured; meanwhile, norepinephrine (NE)
      andadrenaline (EPI) in the blood were detected by ELISA; lactic acid in the tumor
      tissue was determined by colorimetry. And the expression level of LDHA was
      detected by Western blotting. The proliferation of glioma LN229 cells stimulated
      by NE was detected by CCK-8 assay and plate clone formation assay; TranswellTM
      assay was used to test the invasive ability of LN229 cells. The level of LDHA
      mRNA was detected by real-time quantitative PCR. The expressions of LDHA, ERK1/2
      and hypoxia-induced factor-1alpha (HIF-1alpha) were observed using Western
      blotting. By constructing the reporter gene, we studied the mechanism of LDHA
      expression regulated by NE. Results The tumor size and the levels of EPI, NE,
      lactic acid and LDHA in the stress group significantly increased as compared with
      the tumor bearing group. After silencing LDHA, the proliferation rate and lactate
      content decreased. Compared with the control group, the mRNA and protein levels
      of LDHA in NE group was significantly elevated; the phosphorylation levels of HIF
      1alpha and ERK1/2 was significantly raised; and cell proliferation and invasion
      ability were also enhanced. Promoter luciferase reporter assay confirmed that NE
      up-regulated the expression of LDHA by HIF-1alpha. Conclusion Adverse
      psychological stress can promote the proliferation and invasion of glioma cells
      by upregulating LDHA expression.

PMID- 28502302
TI  - [Overexpressed miRNA-134b inhibits proliferation and invasion of CD133+ U87
      glioma stem cells].
AB  - Objective To investigate the role of microRNA-134b (miR-134b) in the
      tumorigenesis of glioma stem cells (GSCs) and the possible molecular mechanism.
      Methods Real-time quantitative PCR (qRT-PCR) was used to evalate the expression
      of miR-134b in CD133+ and CD133- U87 GSCs. A lentiviral vector overexpressing miR
      134b in U87 GSCs was constructed, and the effect of miR-134b overexpression on
      matrix metalloproteinase-2 (MMP-2), MMP-9 and MMP-12 expressions at both mRNA and
      protein levels were detected by qRT-PCR and Western blotting, respectively.
      TranswellTM assay was performed to determine the effect of miR-134b
      overexpression on GSCs invasion ability. Tumor xenograft models in nude mice were
      established to evaluate the effect of miR-134b overexpression on tumorgenesis in
      vivo. Results The qRT-PCR showed that, compared with CD133- cells, miR-134b was
      significantly down-regulated in CD133+ cells. Cell line over-expressing miR-134b
      was successfully established, and miR-134b was up-regulated significantly
      compared with empty vector control. Overexpression of miR-134b remarkably
      inhibited the invasion of U87 GSCs and the expression of MMP-12. However,
      overexpression of miR-134b did not affect MMP-2 and MMP-9 expressions. miR-134b
      also suppressed U87 GSCs xenograft growth in vivo. Tumor volume in tumor
      xenograft model group was significantly lower than that in control group, and
      tumor weight decreased by 42% in the former group. Conclusion Overexpression of
      miR-134b inhibits the growth and invasion of CD133+ GSCs.

PMID- 28502303
TI  - [Effect of metformin on proliferation and apoptosis of rat prolactinoma MMQ cells
      and related mechanisms].
AB  - Objective To investigate the effect of metformin on the cell proliferation, cell
      cycle and apoptosis of rat prolactinoma MMQ cells in vitro and related molecular
      mechanisms. Methods The MMQ cells were treated with 1.25, 2.5, 5, 10, 20 mmol/L
      metformin for 48 hours. CCK-8 assay was used to assess the cell proliferation
      ability; flow cytometry was used to analyze the cell cycle distribution and
      apoptosis; Western blotting was performed to detect the expressions of
      AMPKalpha1/2, p-AMPKalpha, mTOR, p-mTOR, insulin like growth factor 1 receptor
      (IGF-1R), ERK1/2, p-ERK1/2, AKT, p-AKT, P21, CDK4, cyclin D1, caspase-3, cleaved
      caspase-3(c-caspase-3), Bcl-2 and BAX. Results Compared with the control group,
      metformin inhibited cell proliferation, induced cell cycle arrest in the G0/G1
      phase and promoted cell apoptosis in MMQ cells. The expressions of P21 and c
      caspase-3 increased, meanwhile, the expressions of CDK4, cyclin D1, caspase-3 and
      Bcl-2 decreased by metformin. Besides, the expression of p-AMPKalpha was
      elevated, but p-mTOR was reduced. Furthermore, the expressions of IGF-1R, p-AKT
      and p-ERK descended after metformin treatment. Conclusion Metformin could inhibit
      cell proliferation, induce cell cycle arrest and apoptosis in MMQ cells by
      activating AMPK/mTOR signaling pathway and inhibiting IGF-1R signaling pathway.

PMID- 28502304
TI  - [Inula Britannica flower total flavonoids reduces the apoptosis of aging bone
      marrow mesenchymal stem cells by anti-oxidation].
AB  - Objective To investigate the beneficial effect of Inula Britannica flower total
      flavonoids (IBFTF) on aging bone mesenchymal stem cell (BMSC) and its potential
      mechanism. Methods The aging BMSCs were induced by D-galactose, and then treated
      with 12.5, 25, 50 MUg/mL IBFTF. The cell viability was detected by CCK-8 assay.
      The activity of catalase (CAT) and superoxide dismutase (SOD), the content of
      malondialdehyde (MDA) and reactive oxygen species (ROS) were measured by a
      commercial kit. The apoptosis was assessed by flow cytometry. The protein
      expressions of BAX, Bcl-2 and cleaved-caspase-3 (c-caspase-3) were determined by
      Western blotting. Results The cell viability and the activity of SOD and CAT in
      the aging group decreased significantly compared with the normal group, whereas
      different concentrations of IBFTF promoted the cell viability, and simultaneously
      increased the activity of SOD and CAT. The apoptosis, the ROS production, the
      content of MDA, BAX/Bcl-2 ratio and the protein expression of c-caspase-3 in the
      aging group increased obviously compared with the normal group. However, the
      treatment of different concentrations of IBFTF reduced the apoptosis, the ROS
      production, the content of MDA, BAX/Bcl-2 ratio and the protein expression of c
      caspase-3. Conclusion IBFTF can attenuate the apoptosis of aging BMSCs by anti
      oxidation.

PMID- 28502305
TI  - [Shikimic acid inhibits the degranulation and histamine release in RBL-2H3
      cells].
AB  - Objective To study the effects of shikimic acid on the proliferation of rat RBL
      2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism.
      Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells
      treated with 3, 10, 30 MUg/mL shikimic acid. Toluidine blue staining was used to
      observe the degranulation of RBL-2H3 cells. The release of beta-hexosaminidase
      from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 MUg/mL C48/80 was
      determined by substrate assay. ELISA was used to detect the histamine content in
      the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 MUg/mL
      had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was
      a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80
      concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells
      compared with the positive control group, the beta-hexosaminidase release rate
      and histamine release were significantly reduced in RBL-2H3 cells treated with
      shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation
      of RBL-2H3 cells and reduce histamine release.

PMID- 28502306
TI  - [Detection and analysis of immune molecules in leukemia cell surfaces of acute
      promyelocytic leukemia].
AB  - Objective To investigate the immunophenotypic characteristics of acute
      promyelocytic leukemia (APL) and its clinical significance. Methods
      Immunophenotyping was performed by four-color flow cytometry with CD45/SSC-lin
      gating for neoplastic cells and was divided into five levels according to the
      intensity of antigen expression. Results The expression intensity and percentage
      of typical APL phenotypes were: myeloperoxidase (MPO) and CD33 were consistently
      expressed (100%); CD38 (82.35%), CD13 (64.71%), CD64 (50%), CD123 (47.06%) and
      CD117 (44.12%) were partially expressed. HLA-DR (97.06%) and CD34 (99.02%) were
      negative. Post-chemotherapy remission rate in the Lym+APL patients was
      significantly lower than that in the Lym-APL patients. Conclusion The typical
      phenotypic characteristics in APL immunophenotyping were high SSC, CD33+ (grade
      I), CD38+ (grade I), MPO+ (grade I), CD13+ (grade III), CD64+ (grade I/III),
      CD117+ (grade II/III/IV), CD123+ (grade III/IV), CD11b-, HLA-DR-, CD34-.
      Understanding of the immunophenotypic features of APL contributes to rapid
      diagnosis of APL and the guidance of minimal residual disease (MRD) detection.

PMID- 28502307
TI  - [Knock-down of DAB2 interacting protein (DAB2IP) promotes proliferation and
      inhibits apoptosis of bladder cancer cells].
AB  - Objective To study the expression of DAB2 interacting protein (DAB2IP) in human
      bladder cancer tissues and analyze its relationship with pathological grade and
      clinical stage, and observe its role in drug resistance of bladder cancer cells.
      Methods The expression of DAB2IP in primary and recurrent bladder cancers was
      detected by immunohistochemical staining. RNA interference (RNAi) technique was
      used to down-regulate the expression of DAB2IP in 5637 and 253J bladder cancer
      cells. MTT assay and clone formation assay were performed to test the sensitivity
      of cancer cells to pirarubicin. Flow cytometry was done to detect the apoptosis
      rate of low-DAB2IP-expressing cells treated with pirarubicin. Results The
      expression of DAB2IP was negatively correlated with TNM stage, pathological grade
      and lymph node metastasis of bladder cancer. The expression of DAB2IP in the
      recurrent bladder cancer was lower than that in the primary bladder cancer. The
      low expression of DAB2IP in bladder carcinoma cells was related to drug
      resistance. Knock-down of DAB2IP enhanced the colony formation of bladder cancer
      cells, reduced the expressions of PARP and caspase-3, increased expressions of
      Bcl-2 and Mcl-1, reduced the apoptosis of cancer cells and induced chemotherapy
      tolerance. Conclusion Knock-down of DAB2IP can promote the proliferation and
      inhibit the apoptosis of bladder cancer cells, and increase the resistance to
      chemotherapy.

PMID- 28502308
TI  - [Preparation and identification of monoclonal antibody against H1N1 influenza
      virus].
AB  - Objective To prepare the monoclonal antibody (mAb) against influenza A virus
      (H1N1) using purified viral particles as antigen and investigate the
      characterization of host cells infected with influenza virus utilizing the mAb.
      Methods A/PR/8 (H1N1) virus was cultured in embryonated chicken eggs and further
      purified by differential and density gradient centrifugation. The structure of
      viral particles was identified by transmission electron microcopy (TEM).
      Immunogenicity of purified virus was evaluated by Balb/c mice immunized with
      formalin-inactivated virus. Hybridomas secreting mAbs were established through a
      fusion of Sp2/0 myeloma cells and splenocytes from the mice immunized with the
      virus. The characteristics of mAb were identified by ELISA, immunofluorescence
      assay (IFA), Western blotting, hemagglutinin inhibition assay (HI) and
      microneutralization assay. The outside hemagglutinin (HA) on the plasma membrane
      of the host MDCK cells in which the viruses were propagated and the apoptosis of
      MDCK cells infected with the viruses were measured using flow cytometry. Cell
      based ELISA was established using mAb specific to HA. Subsequently, the growth of
      virus was analyzed by cell-based ELISA. Results Transmission electron microscopy
      revealed that the physical structures of the purified virus were spherical,
      elliptical and extended threadlike. Serum IgG titer to influenza virus showed a
      progressive increase, and the IgG titer reached 106 after the immunization for 6
      weeks. Six hybridoma clones secreting mAb specific to A/PR/8 were developed by
      hybridoma technology. The HI and neutralization activities of PR8-10 mAb were
      significantly higher than those of the other mAbs. HI and neutralization titers
      of PR8-10 mAb were 1:2048 and 1:640, respectively. IFA and Western blotting
      confirmed that PR8-10 mAb could recognize HA. Flow cytometry showed that PR8-10
      mAb also recognized HA on the membrane of MDCK in which the viruses were
      replicated and virus infection induced the apoptosis of MDCK cells. Based on the
      previous test results that PR8-10 mAb was able to recognize HA on the membrane of
      the host cells in which the viruses were replicated, cell-based ELISA we
      established was good at analyzing the growth of virus in MDCK cells. Conclusion
      We obtained whole viral particles that were demonstrated to be able to stimulate
      the production of a high IgG titer in a mouse model with formalin-inactivated
      viral particles, and successfully prepared the mAb against H1N1 of high binding
      affinity and neutralization potency. HA-specific mAb can be used to analyze the
      characteristics of virus infection process and the effect of virus infection on
      the host cells as well.

PMID- 28502309
TI  - Effects of vitrification of cumulus-enclosed porcine oocytes at the germinal
      vesicle stage on cumulus expansion, nuclear progression and cytoplasmic
      maturation.
AB  - Although offspring have been produced from porcine oocytes vitrified at the
      germinal vesicle (GV) stage, the rate of embryo development remains low. In the
      present study, nuclear morphology and progression, cumulus expansion, transzonal
      projections (TZPs), ATP and glutathione (GSH) levels were compared between
      vitrified cumulus-oocyte complexes (COCs) and control COCs (no cryoprotectant
      treatment and no cooling), as well as a toxicity control (no cooling).
      Vitrification was performed with 17.5% (v/v) ethylene glycol and 17.5% (v/v)
      propylene glycol. Vitrification at the GV stage caused premature meiotic
      progression, reflected by earlier GV breakdown and untimely attainment of the MII
      stage. However, cytoplasmic maturation, investigated by measurement of ATP and
      GSH levels, as well as cumulus expansion, proceeded normally despite detectable
      damage to TZPs in vitrified COCs. Moreover, treatment with cryoprotectants caused
      fragmentation of nucleolus precursor bodies and morphological changes in F-actin
      from which oocytes were able to recover during subsequent IVM culture. Reduced
      developmental competence may be explained by premature nuclear maturation leading
      to oocyte aging, although other mechanisms, such as initiation of apoptosis and
      reduction of cytoplasmic mRNA, can also be considered. Further research will be
      required to clarify the presence and effects of these phenomena during the
      vitrification of immature COCs.

PMID- 28502310
TI  - Variations in out-of-pocket costs for primary care services across Australia: a
      regional analysis.
AB  - The aim of this study is to describe average out-of-pocket costs across different
      regions of Australia, as defined by Primary Health Network (PHN) boundaries, and
      assess the association between population characteristics and out-of-pocket costs
      for selected primary care services. A combination of descriptive and regression
      analysis was undertaken using administrative data from the Australian Department
      of Human Services reporting on the health services used across PHNs in Australia.
      Those in regional areas paid significantly more for Allied Health services than
      those in capital cities (A$5.68, P=0.006). The proportion of an area's population
      aged 65 years and over was inversely related to out-of-pocket charges for Allied
      Mental Health (-A$79.12, P=0.029). Some areas had both high charges and
      disadvantaged populations: Country South Australia, Northern Queensland, Country
      Western Australia, Tasmania and Northern Territory, or populations with poor
      health: Northern Territory and Tasmania. Although there was a large amount of
      variation in out-of-pocket charges for primary care services between PHNs in
      Australia, there was little evidence of inequality based on health, age and
      socioeconomic characteristics of a population or the proportion of Aboriginal and
      Torres Strait Islander people.

PMID- 28502312
TI  - Sudden Visual Shadow in a 70-Year-Old Man.

PMID- 28502313
TI  - Preventing Binge Drinking in Adolescents.
AB  - BACKGROUND: In a survey taken in Germany in 2015, 14.1% of the 12- to 17-year
      olds surveyed had practiced binge drinking at least once in the preceding 30
      days. The school program "Klar bleiben" ("Keep a Clear Head") was designed for
      and implemented among 10th graders. The participants committed themselves to
      abstain from binge drinking for 9 weeks. We studied whether this intervention
      influenced the frequency and intensity of binge drinking. METHODS: This cluster
      randomized controlled trial was carried out in 196 classes of 61 schools, with a
      total of 4163 participants with a mean age of 15.6 years (standard deviation 0.73
      years). Data were collected by questionnaire in late 2015, before the
      intervention and again six months later. The primary endpoints were the frequency
      of consumption of at least 4 or 5 alcoholic drinks (for girls and boys,
      respectively) and the typical quantity consumed. This trial was registered in the
      German Clinical Trials Registry (Deutsches Register Klinischer Studien, DRKS)
      with the DRKS ID number DRKS00009424. RESULTS: At the beginning of the trial,
      there was no difference between the intervention group and the control group with
      respect to the primary endpoints. After the intervention, differences were found
      among participants who had consumed alcohol before the trial (73.2% of the
      overall sample): binge drinking at least once in the preceding month was reported
      by 49.4% of the control group and by 44.2% in the intervention group (p = 0.028).
      The mean number of alcoholic drinks consumed in each drinking episode was 5.20 in
      the control group and 5.01 in the intervention group (p = 0.047). CONCLUSION: The
      intervention was effective only in the large subgroup of adolescents who had
      previously consumed alcohol: they drank alcohol less often and in smaller amounts
      than their counterparts in the control group.

PMID- 28502314
TI  - Important Risk Factors Were Not Included.

PMID- 28502315
TI  - In Reply.

PMID- 28502311
TI  - Tracheotomy-Related Deaths.
AB  - BACKGROUND: Tracheotomies are frequently performed on ventilated patients in
      intensive care and sometimes lead to fatal complications. In this article, we
      discuss the causes and frequency of death associated with open surgical
      tracheotomy (OST) and percutaneous dilatational tracheotomy (PDT) on the basis of
      a review of the pertinent literature. METHODS: We systematically searched the
      PubMed, EMBASE, and Cochrane Library databases and the Karlsruhe Virtual Catalog
      for publications (1990-2015) on tracheotomy-related deaths in adults, using the
      search terms "tracheotomy" and "tracheostomy." 39 relevant dissertations were
      included in the analysis as well. RESULTS: 109 publications were included. Of the
      25 056 tracheotomies described, there were 16 827 PDTs and 7934 OSTs; for 295
      tracheotomies, the technique used was not stated. 352 deaths were reported,
      including 113 in patients treated with PDT, 49 in those treated with OST, and 190
      deaths related to a tracheotomy without specification of the method used. The
      frequency of death among patients with OST and those treated with PDT was
      similar: 0.62% for OST (95% confidence interval [0.47; 0.82]) and 0.67% for PDT
      ([0.56; 0.81]). The most common causes of death and their frequencies, as a
      percentage of all tracheotomies, were hemorrhage (OST: 0.26% [0.17; 0.40], PDT:
      0.26% [0.19; 0.35]), loss of airway (OST: 0.21% [0.13; 0.34], PDT: 0.20% [0.14;
      0.28]), and false passage (OST: 0.11% [0.06; 0.22], PDT: 0.20% [KI 0.15; 0.29]).
      CONCLUSION: Bias in the data cannot be excluded, as these were not epidemiologic
      data and the documentation was found to be incomplete. The likelihood of a fatal
      complication seems to be the same with both tracheotomy techniques as far as can
      be determined from the available evidence. Tracheotomy-related deaths can be
      avoided in several ways: by thorough training under the leadership of experienced
      physicians, by the use of the World Health Organization's Surgical Safety
      Checklist regardless of where the tracheotomy is performed, and by the continuous
      vigilance of nursing staff.

PMID- 28502316
TI  - Hyponatremia Is a Common Cause.

PMID- 28502317
TI  - In Reply.

PMID- 28502318
TI  - Look Out-A Trap in the Cardiac Cath Lab.

PMID- 28502319
TI  - An unusual case of a young patient with Whipple's disease involving the central
      nervous system.

PMID- 28502320
TI  - Atypical teratoid rhabdoid tumor arising in a pleomorphic xanthoastrocytoma: a
      rare entity.
AB  - Atypical teratoid rhabdoid tumor (AT/RT) is a rare and aggressive tumor usually
      occurring at younger ages. Pleomorphic xanthoastrocytomas (PXA) on the other hand
      are quiescent tumors with benign behavior. AT/RTs arising in the setting of PXA
      are exceptional. We present the case of a 23-year-old female patient, the fourth
      in the literature, speculated as having AT/RT arising within a PXA, as
      demonstrated by the presence of INI1 mutation. The patient presented with a short
      history of headache, which increased over time, and emerging seizures. She had a
      contrast-enhancing mass in the left temporal area demonstrated by MRI.
      Pathological examination demonstrated a dimorphic tumor containing a spindle
      pleomorphic component reminiscent of PXA and a rhabdoid component with INI1 loss
      showing features of AT/RT. Both components shared the same BRAF mutation,
      supporting their common origin, and hence the case was speculated as an AT/RT
      arising in the setting of a PXA by secondary genetic change of inactivation of
      INI1. She had a poor outcome despite surgery and died 8 months after her
      diagnosis.?.

PMID- 28502321
TI  - Cytomegalovirus in the human dentate gyrus and its impact on neural progenitor
      cells: report of two cases.
AB  - Congenital cytomegalovirus (CMV) infection in the 2<sup>nd</sup> and
      3<sup>rd</sup> trimester results in catastrophic CNS abnormalities. This
      susceptibility is thought to result from the high proportion of neural stem cells
      in the developing brain. In immunocompromised adults, CNS infection by CMV
      preferentially affects ependymal surfaces, from where it expands to involve the
      parenchyma. Experimental models of murine CMV infection demonstrate viral tropism
      for the dentate gyrus (DG) and subventricular zone, the areas in which adult
      neurogenesis occurs. We present two cases of CMV infection of the DG of
      immunocompromised allogeneic stem cell transplant recipients. Both cases showed
      CMV-positive neurons in the DG granular cell layer, as well as contiguous layers.
      The majority of infected cells contained Nissl substance and expressed nestin,
      glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and
      neurofilament. These cases demonstrate that CMV infects the DG in humans. Co
      expression of nestin and GFAP, indicative of early neurogenesis, is consistent
      with experimental models showing neural stem cells as the target of CMV,
      providing further histological evidence of neurogenesis in the human dentate.
      Finally, the cases suggest that CMV infection produces abnormal migration of
      newly formed neurons as evidenced by the finding of virally infected neurons in
      the molecular layer of the dentate.?.

PMID- 28502322
TI  - High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross
      sectional and longitudinal study?.
AB  - AIMS: Many of the secondary effects of high levels of molybdenum (Mo) overlap
      with symptoms commonly seen in pediatric patients with chronic kidney disease
      (CKD). We measured plasma Mo levels and examined the relationship between Mo
      levels and kidney function. MATERIALS AND METHODS: The study was carried out at
      the London Health Sciences Centre in London, Ontario, Canada with 36 children and
      adolescents 4 - 18 years of age with CKD. There were 1 - 6 trace element
      measurements (Mo and copper (Cu)) per patient. We studied the proportion of
      patients with abnormal trace element levels and the relationship between trace
      element levels and estimated glomerular filtration rate (eGFR), calculated using
      the Filler formula. Plasma Mo and Cu levels were measured using High Resolution
      Sector Field Inductively Coupled Mass Spectrometry. Anthropomorphic data and
      blood parameters were collected from our electronic chart program. RESULTS:
      Median eGFR was 51 mL/min/1.73m<sup>2</sup> (35, 75). Median Mo level was 2.00
      ug/L (1.40, 2.88). 20 patients had at least one set of Mo levels above the
      published reference interval in either unit, and the results of 46% of the tests
      were above the interval. There was a strong negative correlation between the Mo
      levels and the eGFR (Spearman's r = -0.627, p < 0.0001). CONCLUSIONS: Our study
      suggests that pediatric patients with CKD have elevated plasma levels of Mo,
      which may cause secondary effects commonly associated with CKD. The elevated Mo
      levels in our center's catchment area may cause an accumulation of this trace
      element in patients with impaired renal function.?.

PMID- 28502323
TI  - A case report on the exceptional coincidence of two inherited renal disorders:
      ADPKD and Alport syndrome?.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic
      cause of dialysis-requiring end-stage renal disease in adults and is
      characterized by the slowly progressing replacement of renal tissue by focal
      macrocysts. Alport syndrome (AS; hereditary nephritis) is a rare, inherited
      disorder of the basement membrane associated with hematuria, proteinuria, and
      loss of kidney function as well as sensorineural hearing loss and ocular
      abnormalities. Here, we report on a family in which both ADPKD and AS are
      present. In a male patient, both -ADPKD and AS coincided. This patient shows the
      very rare coexistence of two severe, inherited renal disorders and illustrates
      the importance of considering additional diagnoses in the setting of positive
      family history for a common hereditary disorder.?.

PMID- 28502324
TI  - Favorable long-term outcomes of isolated liver transplantation in a child with
      atypical hemolytic uremic syndrome caused by a novel complement factor H
      mutation?.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by
      microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury that
      is usually caused by complement dysregulation. Complement factor H (CFH) is a
      regulator of the complement system produced in the liver, and CFH gene mutations
      are the most frequent causes of aHUS. To date, the therapeutic options for aHUS
      with CFH mutations have consisted of plasma infusions, plasma exchange, kidney
      transplantation, isolated liver transplantation, or combined liver and kidney
      transplantation. Recently, eculizumab, a humanized monoclonal antibody directed
      against complement C5, has been proven to be effective against aHUS. However,
      life-long eculizumab maintenance therapy is usually required for aHUS; therefore,
      other curative options should be considered. We describe a case of neonatal onset
      aHUS caused by a novel mutation of CFH and treated with an isolated liver
      transplantation at the age of 24 months. Nearly 5 years post-transplant, the
      patient's health has been generally good without evidence of aHUS. This case
      report suggests that isolated liver transplantation in aHUS patients with CFH
      mutations and preserved eGFR could be a curative therapeutic option in contrast
      to long-term eculizumab therapy.?.

PMID- 28502325
TI  - Long-term Mortality in Hospitalized Patients With Community-Acquired Pneumonia.

PMID- 28502326
TI  - K+ and Mg2+ Dyshomeostasis in Acute Hyperadrenergic Stressor States.
AB  - Acute stressor states are linked to neurohormonal activation that includes the
      adrenergic nervous system. Elevations in circulating epinephrine and
      norepinephrine unmask an interdependency that exists between K+ and Mg2+ based on
      their regulation of a large number of Mg2+-dependent Na+-K+-ATPase pumps present
      in skeletal muscle. The hyperadrenergic state accounts for a sudden translocation
      of cations into muscle with the rapid appearance of hypokalemia and
      hypomagnesemia. The resultant hypokalemia and hypomagnesemia will cause a delay
      in myocardial repolarization and electrocardiographic QTc prolongation raising
      the propensity for supraventricular and ventricular arrhythmias. In this review,
      we focus on the interdependency between K+ and Mg2+, which is clinically relevant
      to acute hyperadrenergic stressor states found in patients admitted to intensive
      care units.

PMID- 28502327
TI  - Fanconi Anemia and Laron Syndrome.
AB  - BACKGROUND: Fanconi anemia (FA) is a condition characterized by genetic
      instability and short stature, which is due to growth hormone (GH) deficiency in
      most cases. However, no apparent relationships have been identified between FA
      complementation group genes and GH. In this study, we thereby considered an
      association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF
      1] deficiency). METHODS: A 21-year-old female Mexican patient with a genetic
      diagnosis of FA was referred to our research department for an evaluation of her
      short stature. Upon admission to our facility, her phenotype led to a suspicion
      of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed
      and a GH stimulation test was performed. In addition, we used a next-generation
      sequencing approach for a molecular evaluation of FA disease-causing mutations
      and genes involved in the GH-IGF signaling pathway. RESULTS: Tests revealed low
      levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as
      well as a lack of response to GH stimulation. Sequencing confirmed a defect in
      the GH receptor signaling pathway. CONCLUSIONS: To the best of our knowledge,
      this study is the first to suggest an association between FA and LS. We propose
      that IGF-1 administration might improve some FA complications and functions based
      upon IGF-1 beneficial actions observed in animal, cell and indirect clinical
      models: erythropoiesis modulation, immune function improvement and metabolic
      regulation.

PMID- 28502328
TI  - The Association Between Endocan Levels and Subclinical Atherosclerosis in
      Patients With Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Proinflammatory conditions induced by circulating factors in diabetes
      play a pivotal role in endothelial dysfunction and related vascular
      complications. Endothelial cell-specific molecule-1 or endocan is a dermatan
      sulfate proteoglycan secreted primarily by the vascular endothelium. Although
      endocan has been shown to be a potential biomarker in coronary heart disease, its
      role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In
      this study, we investigated the correlation between serum endocan levels and
      subclinical AS in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND
      METHODS: Patients (n = 69) with T2DM were included. All the patients were
      stratified based on the absence (n = 42) or presence (n = 27) of subclinical AS.
      Healthy subjects (n = 28) served as controls. Serum levels of endocan, fasting
      blood glucose, glycosylated hemoglobin A1, high-sensitivity C-reactive protein
      and carotid intima-media thickness (cIMT) were measured. RESULTS: Endocan levels
      were significantly elevated in both the T2DM (0.89 +/- 0.28ng/mL) and T2DM with
      subclinical AS (1.20 +/- 0.33ng/mL) groups relative to the control group (0.68 +/
      0.24ng/mL) (P < 0.05 for all). Endocan levels were also positively correlated
      with glycosylated hemoglobin A1, fasting blood glucose and cIMT (r = 0.292, P =
      0.004; r = 0.224, P = 0.027 and r = 0.496, P < 0.001, respectively). In addition,
      endocan levels were independently associated with cIMT (beta = 0.220, t = 5.816,
      P = 0.000) and were a significant risk factor for T2DM with subclinical AS (odds
      ratio = 1.98, 95% CI: 1.43-2.73, P < 0.001). CONCLUSIONS: These findings suggest
      that serum endocan levels may be a useful biomarker for the early diagnosis of
      subclinical AS in patients with T2DM.

PMID- 28502329
TI  - Serum Adipocytokine Levels as Surrogate Markers for Disease Activity of Crohn's
      Disease.
AB  - BACKGROUND: Determining inflammatory activity is crucial for assessing disease
      activity and for tailoring therapy in patients with Crohn's disease (CD). This
      study aimed to evaluate adipocytokine levels in patients with CD and to determine
      whether they can serve as surrogate markers for disease activity. MATERIALS AND
      METHODS: Serum samples and information regarding the clinical features of
      patients in the CD Network Project registry were collected from March 2009 to
      February 2012. Patients with CD and disease duration of at least 2 years were
      enrolled in this study. Fasting serum leptin, adiponectin, obestatin and ghrelin
      levels were measured, and their correlation with clinical features of the
      patients was analyzed. Serum adipocytokine levels were evaluated according to
      disease activity as determined by CD activity index score. RESULTS: A total of
      153 patients with CD were included. Serum ghrelin levels negatively correlated
      with patient age (P = 0.041) and age at diagnosis (P = 0.017), and positively
      correlated with C-reactive protein (CRP) levels (P = 0.017). Multiple regression
      analysis showed that serum ghrelin levels were related only to CRP levels (P =
      0.032). Like ghrelin, serum leptin levels were also related to CRP levels (P <
      0.001). Obestatin and adiponectin levels were not related to CRP levels. Serum
      adipocytokine levels did not significantly differ across different disease
      locations or behaviors. Serum ghrelin levels were significantly lower in patients
      with CD with a history of surgery than in those without (P = 0.007). CONCLUSIONS:
      Serum ghrelin and leptin levels may be useful as surrogate markers for disease
      activity in patients with CD.

PMID- 28502330
TI  - Three Decades of Follow-up of Adults After Recovery From Invasive Pneumococcal
      Pneumonia.
AB  - BACKGROUND: Streptococcus pneumoniae infection is the most common cause of
      community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD)
      carries a high case fatality rate. We investigated the lifespan of adults who
      recovered from IPD during a 32-year follow-up. MATERIALS AND METHODS: We
      determined whether adults discharged after an episode of IPD from hospitals
      affiliated with the Marshall University Joan C. Edwards School of Medicine in
      Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan
      was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate
      analysis, life expectancy using life tables for West Virginia, years of potential
      life lost and serotype occurrence. RESULTS: The study group comprised 155 adults
      who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan
      after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age
      at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%)
      patients lived longer than their life expectancy. Of the 13 comorbid diseases
      analyzed, cancer and neurologic diseases and the number of comorbid diseases
      suffered by each patient were the significant variables associated with survival.
      The mean years of potential life lost was 9.936 years. Only serotype 12 of 31
      serotypes recovered occurred more often in patients who survived for 11 or more
      years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95). CONCLUSIONS: The
      fact that most adult patients who recovered from IPD died before their documented
      life expectancy argues for the pernicious severity of IPD and the importance of
      immunization of adults with pneumococcal vaccines.

PMID- 28502331
TI  - Risk Factors and Outcomes of Acute Kidney Injury in Patients With Hepatitis B
      Virus-Related Acute-on-Chronic Liver Failure.
AB  - BACKGROUND: Acute kidney injury (AKI) is common in patients with hepatitis B
      virus (HBV)-related acute-on-chronic liver failure (ACLF); however, few studies
      concerning the risk factors and recovery patterns of renal function have been
      published. MATERIALS AND METHODS: A retrospective analysis of 150 patients with
      HBV-ACLF was performed. The occurrence, risk factors and functional recovery of
      AKI among patients with HBV-ACLF were investigated. RESULTS: A total of 90
      patients (60%) with HBV-ACLF developed AKI. Patients with AKI had higher creatine
      kinase (P = 0.004), total bilirubin (P = 0.039), HBV viral load (P = 0.044),
      serum creatine (P < 0.001) and model for end-stage liver disease (MELD) score (P
      < 0.001) values and a higher proportion of hepatic encephalopathy (P = 0.032) and
      spontaneous bacterial peritonitis (SBP) (P = 0.042) than patients without AKI.
      Logistic regression analysis illustrated that SBP (odds ratio = 6.214, P = 0.012)
      and MELD score (odds ratio = 1.097, P = 0.006) were risk factors for the
      development of AKI. A subgroup analysis of recovery patterns in renal function
      showed that patients with a severe AKI stage had worse outcomes (P = 0.007). The
      proportion of patients who experienced a complete recovery was higher in
      survivors than in the overall AKI populations (P = 0.004). Follow-up studies
      showed that the no-AKI group had a higher transplant-free survival rate than the
      AKI group at day 90 (80.0% versus 26.7%, respectively, P < 0.001). The survival
      rate among patients with AKI Stage 1 was higher than that of patients with AKI
      Stage 2 and patients with AKI Stage 3 (P < 0.001). CONCLUSIONS: AKI is common in
      patients with HBV-ACLF. The SBP and MELD score have some prognosis value for
      patients with AKI. AKI and its stages affect the 90-day transplant-free mortality
      rate. It is important to focus on exploring the early recognition of AKI and
      early intervention of those risk factors in individuals with HBV-ACLF.

PMID- 28502333
TI  - Zika Virus: Epidemiology, Pathogenesis and Human Disease.
AB  - The Zika virus is a positive sense, single-stranded RNA arbovirus in the
      Flaviviridae family, genus Flavivirus. This virus was initially isolated in
      Africa and is transmitted to nonhuman primates and humans by mosquitoes. Initial
      reports describe sporadic mild viral infection with fever, arthralgia, myalgia
      and conjunctivitis in Africa and Asia. However, its geographic distribution has
      significantly increased, and it has caused large outbreaks in the Yap Islands in
      2007, in French Polynesia in 2013 and in Brazil in 2015. Multiple cases of
      Guillain-Barre' syndrome occurred in French Polynesia and Columbia during
      outbreaks, and infections in pregnant women in Brazil have been associated with
      microcephaly and fetal loss. The viremic phase in humans is short, and diagnosis
      usually depends on positive immunoglobulin M titers with serum neutralization
      tests for confirmation. Treatment is directed at symptoms; there are no antiviral
      drugs available. Transmission can also occur through sexual contact with infected
      men and through blood transfusion. Prevention is important in women and includes
      limiting travel to endemic areas when possible, control of mosquito populations
      and condom use when appropriate. The Centers for Disease Control and Prevention
      is actively involved in tracking these infections and providing up-to-date
      information.

PMID- 28502332
TI  - The Enhanced International Prognostic Index for Diffuse Large B-cell Lymphoma.
AB  - OBJECTIVE: To explore the prognostic value of the enhanced International
      Prognostic Index (NCCN-IPI) for Asian patients with diffuse large B-cell lymphoma
      (DLBCL) treated in the rituximab era. MATERIALS AND METHODS: We performed a
      retrospective analysis of 176 patients with newly diagnosed DLBCL. The estimated
      overall survival (OS) and progression-free survival (PFS) of the different risk
      groups were discriminated by the International Prognostic Index (IPI), the
      revised International Prognostic Index (R-IPI) and the NCCN-IPI. RESULTS: With a
      median follow-up of 18 months, at 3 years, the OS was 73% and the PFS was 65%.
      The 3-year OS for the 4 NCCN-IPI risk groups were 91% versus 80% versus 57%
      versus 45% (P < 0.001); the 3-year PFS were 77% versus 72% versus 56% versus 26%
      (P < 0.001). The 3-year OS of the 4 risk groups discriminated by the IPI ranged
      from 85-55% (P < 0.001); the 3-year PFS ranged from 81-41% (P < 0.001). The 3
      year OS of the 3 distinct prognostic groups by the R-IPI ranged from 86-51% (P <
      0.001); the 3-year PFS ranged from 86-47% (P < 0.001). The 3-year OS and PFS of
      the high-risk group according to the NCCN-IPI were lower than the IPI and R-IPI.
      Using the NCCN-IPI, the outcomes among the risk groups spanned a large range, and
      the survival of the high-risk group was significantly different from the high
      intermediate risk group. CONCLUSIONS: The NCCN-IPI is a clinically useful
      prognostic index for patients with DLBCL treated in the rituximab era, especially
      for high-risk patients.

PMID- 28502334
TI  - AP-1 Expression and its Clinical Relevance in Immune Disorders and Cancer.
AB  - The inflammatory response is known to have a significant role in certain
      autoimmune diseases and malignancies. We review current knowledge regarding the
      functions of activator protein 1 (AP-1) as an important modulator in several
      immune disorders and carcinomas. AP-1 is overexpressed in rheumatoid arthritis
      and in long-term allogeneic hematopoietic stem cell transplantation survivors;
      however, decreased expression of AP-1 has been observed in psoriasis, systematic
      lupus erythematosus and in patients who do not survive after hematopoietic stem
      cell transplantation. AP-1 also is implicated in the control of various cancer
      cells. Higher levels of AP-1 components are present in breast and endometrial
      carcinomas, colorectal cancer and in acute myeloid leukemia, Hodgkin's lymphoma
      and anaplastic large cell lymphoma, with downregulation in ovarian and gastric
      carcinomas and in patients with chronic myelogenous leukemia. AP-1 may enable the
      development of helpful markers to identify early-stage disease or to predict
      severity.

PMID- 28502335
TI  - Limb-Girdle Muscular Dystrophy 2B and Miyoshi Presentations of Dysferlinopathy.
AB  - We report the following 2 subtypes of progressive limb-girdle dystrophy type 2B:
      limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi. The first patient
      described had weakness in the anterior thigh muscles (LGMD2B) and the second
      patient had calf muscle weakness and atrophy (Miyoshi). Literature review was
      performed and LGMD2B was compared and distinguished from other myopathies of
      similar nature. Genetic testing with polymerase chain reaction analysis of the
      DYSF gene confirmed the diagnosis in both patients. Additional findings of
      histopathology, specific stain for sarcolemmal membrane protein, Western blot
      analysis and clinical presentation clinched the diagnosis further of
      dysferlinopathy (LGMD2B) in both our patients. Currently, there is no definitive
      treatment on the horizon and immunosuppressive therapy is not recommended for
      this condition. Gene therapy may have a future role, but at present, muscle
      strengthening exercises and patient awareness are the mainstays.

PMID- 28502336
TI  - Silicone Injection-Related Granulomatous Hypercalcemia.
AB  - Cosmetic filler injections are known to cause a number of acute and chronic
      effects, including local inflammation, nodule formation and granulomatous
      reaction. The timeline of these events is highly variable, occurring from hours
      to decades following injection. In few cases, systemic effects have been
      observed. We report a case of granulomatous disease secondary to illicit silicone
      injection causing recalcitrant hypercalcemia. Additionally, we review the
      pathophysiology of inflammation in cosmetic filler injections, the prevailing
      understanding of hypercalcemia in granulomatous disease and summarize the most
      effective treatment modalities for this rare condition.

PMID- 28502337
TI  - Successful Treatment of Central Nervous System Vasculitis Associated with
      Relapsing Polychondritis With Cyclophosphamide.

PMID- 28502338
TI  - Diabetes as First Manifestation of Autoimmune Pancreatitis.

PMID- 28502339
TI  - Atypical Common Carotid Artery Diaphragm With an Accompanying Aneurysm.

PMID- 28502340
TI  - Glossodynia After Osteoporosis Treatment.

PMID- 28502341
TI  - Cigar-Shaped Intramuscular Calcifications.

PMID- 28502343
TI  - Intrathymic Parathyroid Adenoma.

PMID- 28502342
TI  - Emphysematous Pyelitis: An Entity Distinct from Emphysematous Pyelonephritis.

PMID- 28502344
TI  - Cement Pulmonary Embolism.

PMID- 28502346
TI  - Kinematics and Function of Total Ankle Replacements Versus Normal Ankles.
AB  - End-stage ankle arthritis produces severe functional disability, quantifiable by
      gait abnormalities. In all categories of gait parameters, total ankle
      arthroplasty (TAA) satistically significantly improves function, compared to
      patients' preoperative function. There are increases in step length, cadence and
      velocity; in sagittal plane motion of the ankle, as well has hip and knee motion,
      and in ankle power and moment. These functional gait improvements correspond to
      clinical improvements of pain relief and satisfaction. Although these
      improvements fail to reach the functional performance of healthy controls, the
      improvement over preoperative function is clinically meaningful and statistically
      significant.

PMID- 28502345
TI  - An Intriguing Case of Purple Urine Bag Syndrome.

PMID- 28502347
TI  - Ankle Arthrodesis Versus Total Ankle Arthroplasty.
AB  - Reoperation rates are higher in total ankle arthroplasties (TAAs) compared with
      ankle arthrodesis. Infection rates for primary TAAs are 1.4% to 2.4%. The
      survival rate of TAA is approximately 75% to 90% at 10 years. Arc of motion is
      maintained with TAAs compared with ankle arthrodesis. Ankle arthrodesis increases
      arc of motion through the talonavicular joint. Several factors are strong reasons
      to favor ankle fusion rather than TAA. TAA and ankle arthrodesis are effective
      treatments of end-stage ankle arthritis but the choice must be tailored to
      individual patients.

PMID- 28502348
TI  - Osteolysis in Total Ankle Replacement: How Does It Work?
AB  - Aseptic loosening of implants remains the most common reason for revision surgery
      for hip, knee, or ankle prostheses. Although a great scientific effort has been
      made to explain the underlying mechanisms it remains poorly understood, complex,
      and multifactorial. Many factors, including age, body weight, activity lesions,
      implant design, fixation methods, material proprieties, immunologic responses,
      and biomechanical adaptations to total ankle replacement all contribute to the
      development of periprosthetic osteolysis.

PMID- 28502349
TI  - Total Ankle Replacement in the Presence of Talar Varus or Valgus Deformities.
AB  - Patients presenting with end-stage ankle arthritis with coronal plane talar
      deformities have a variety of complex multidirectional deformities that require
      careful preoperative assessment and a clear understanding of the pathophysiology.
      Surgeons managing these patients with total ankle arthroplasty need to be
      familiar with extra-articular and intra-articular surgical methods to correct pes
      planus and pes cavus deformities, including bony procedures and soft tissue
      procedures. Performing these procedures in 1 or 2 stages depends on surgeon
      preference and the severity of the deformities. This article recommends a two
      staged reconstruction for more severely deformed feet.

PMID- 28502350
TI  - Current Update in Total Ankle Arthroplasty: Salvage of the Failed Total Ankle
      Arthroplasty with Anterior Translation of the Talus.
AB  - Ankle replacement results may be compromised by malposition of the components. An
      anterior displacement can be measured on a lateral standing radiograph. The ankle
      may appear anteriorly translated because the ankle is overstuffed, the heel cord
      is tight, or the posterior capsule is tight. In ankle instability with
      degenerative arthritis, the talus may be anteriorly translated, internally
      rotated, and in varus. In an ankle replacement, this deformity may persist and
      will require correction. On occasion, the talus is inserted too anterior;
      revision to a flat cut talar component and posterior translation of the talar
      component will result in correction.

PMID- 28502351
TI  - Malalignment Correction of the Lower Limb Before, During, and After Total Ankle
      Arthroplasty.
AB  - One of the main challenges in ankle replacement is correction of any deformities
      in the operative limb. Deformity can be found proximal and distal to the ankle
      joint as well as in the ankle joint. There are static and dynamic deformities
      that can create unbalanced ankle joints causing early and often catastrophic
      failure. Surgeons must recognize the deformities that are present and use sound
      judgment to balance the ankle joint with procedures before, during, or after
      total ankle implantation. This article helps clinicians to identify deformity and
      provides a basic template to consider how to address each challenge.

PMID- 28502352
TI  - Revision of Stemmed Agility Implants.
AB  - Total ankle arthroplasty has advanced rapidly in the last 20 years. Early agility
      implants enjoyed improved survivability compared with more archaic total ankle
      implants. When talar subsidence occurs, the revision options include a stemmed
      component to improve stability by spanning the subtalar joint. Removal and
      revision of these stemmed components can be difficult because of ingrowth and
      bone loss.

PMID- 28502353
TI  - Management of Talar Component Subsidence.
AB  - Component subsidence has been found to be the top complication that leads to
      failure of the total ankle arthroplasty (TAA). The cause of subsidence formation
      is unclear, and is multifactorial. Talar subsidence is more frequently met than
      tibial subsidence, and the subsequent big bone loss is demanding to handle. As a
      revision treatment option, neither a revision TAA nor a salvage ankle and/or
      hindfoot arthrodesis procedure is easy to perform or can obtain a definite
      outcome. The Salto XT can be used to treat most of the TAA systems available for
      use in the United States with acceptable short-term outcomes.

PMID- 28502354
TI  - Soft Tissue Reconstruction After Total Ankle Arthroplasty.
AB  - Wound complications following total ankle replacement are common. A team
      approach, including plastic surgeons, should be utilized to manage these wound
      issues. The handling of the wound, from the index procedure, to a variety of
      flaps, can be utilized to provide a successful outcome following an ankle
      replacement.

PMID- 28502355
TI  - How To Diagnose and Treat Infection in Total Ankle Arthroplasty.
AB  - Periprosthetic infection after total ankle arthroplasty (TAA) is a serious
      complication, often requiring revision surgery, including revision arthroplasty,
      conversion to ankle arthrodesis, or even amputation. Risk factors for
      periprosthetic ankle infection include prior surgery at the site of infection,
      low functional preoperative score, diabetes, and wound healing problems. The
      clinical presentation of patients with periprosthetic ankle joint infection can
      be variable and dependent on infection manifestation: acute versus chronic. The
      initial evaluation in patients with suspected periprosthetic joint infections
      should include blood tests: C-reactive protein and erythrocyte sedimentation
      rate. Joint aspiration and synovial fluid analysis can help confirm suspected
      periprosthetic ankle infection.

PMID- 28502356
TI  - Dealing with the Stiff Ankle: Preoperative and Late Occurrence.
AB  - In patients with a stiff ankle replacement, appropriate resection of scarred
      capsular structures, hypertrophic bone debridement, and careful release of
      tendons should be performed to achieve good outcomes. Appropriately sized and
      correctly implanted components are required to restore ankle function to as
      normal as possible. Although not proven, the better a total ankle replacement is
      balanced, the less likely scar and heterotopic bone formation will occur. In
      patients with a stiff and painful ankle replacement, a preoperative diagnostic
      workup is mandatory to understand the underlying pathologic process and plan
      appropriate treatment. All underlying causes should be addressed.

PMID- 28502357
TI  - Experience with Navigation in Total Ankle Arthroplasty. Is It Worth the Cost?
AB  - Optimal placement of correctly sized total ankle replacement (TAR) implants is
      elemental to prolonging the working life. The negative mechanical effects of
      implant malalignment are well characterized. There is one FDA-approved navigated
      TAR system with limited but encouraging outcomes data. Therefore, its value can
      be estimated only based on benefits other than a proven clinical outcomes
      improvement over conventional systems. These include unique preoperative planning
      through 3-dimensional templating and virtual surgery and the patient-specific cut
      guides, which also reduce overall instrumentation needed for the case. To better
      inform this conversation, well-observed longitudinal outcomes studies are
      warranted.

PMID- 28502358
TI  - Is There Anything to Learn from a National Joint Registry?
AB  - National joint registries (NJRs) have been established in Northern Europe for
      over 20 years. Since then, many other countries have begun collecting and
      reporting national data for total ankle arthroplasty (TAA). With relatively small
      numbers implanted, a large variety of available designs, and with any long-term
      reports dominated by designer groups, TAA is ideally placed to benefit from large
      national or even pooled national registries. This article reviews the existing
      registry-based literature with respect to what is already known. The potential
      positives and down sides of registry data also are highlighted.

PMID- 28502359
TI  - Pearls and Pitfalls for a Surgeon New to Ankle Replacements.
AB  - The role of the surgeon learning curve in total ankle replacement (TAR) has
      produced contradictory results. It is important for a new surgeon to know what
      clinical and radiological parameters are considered reliable and ideal. It is
      clear that exposure to a high-volume center will increase the reliability of a
      new surgeon approaching TAR. Implant choice may be influenced by surgeon
      training, and the debate of mobile versus fix-bearing prosthesis is still open.
      Anterior versus lateral approach is still an open debate, with any hypothetical
      advantages given by the direct vision on the center of rotation to be proven.

PMID- 28502360
TI  - Preface.

PMID- 28502361
TI  - Measuring and accounting for the Hawthorne effect during a direct overt
      observational study of intensive care unit nurses.
AB  - BACKGROUND: Because suspecting nurses could alter hand hygiene (HH) behavior when
      observed, the goal of this article was to describe how the Hawthorne effect (HE)
      was measured and accounted for in a direct observational prospective study.
      METHODS: Observations were made 8 h/d for 3-5 days in 5 intensive care units
      (ICUs) (4 hospitals) on a convenience sample of 64 ICU nurses in Texas. The HE
      was measured so if hand hygiene adherence rates of the first 2 hours were 20%
      higher than the last 6 hours, the first 2 hours would be dropped and an
      additional 2 hours would be added at the end of the observation period. Hourly
      rates were recorded during the observation period, using room entry and room
      exit. RESULTS: The difference between aggregated rates of the first 2 hours and
      last 6 hours was 0.56% (range, 0.02%-15.74%) and not significant. On 12
      observation days, higher rates were observed during the first 2 hours. On 6 days,
      higher rates were observed in the last 6 hours, with difference in rates of 1.43%
      (day 1), 2.97% (day 2), and 1.42% (day 3). CONCLUSIONS: The attempt at measuring
      and accounting for the HE showed little difference in HH rates throughout the
      observation period. Based on these results, necessity of the observer moving
      locations during HH surveillance after 10-20 minutes, because of a feared HE,
      might not be necessary.

PMID- 28502362
TI  - [When to start, how to manage and when to stop non-invasive ventilation during
      acute COPD exacerbation?]

PMID- 28502363
TI  - [Weaning from mechanical ventilation. Role of conventional methods and non
      invasive ventilation for weaning].

PMID- 28502364
TI  - [Which inhaled pharmacological treatments for COPD acute exacerbations in
      hospital?]

PMID- 28502365
TI  - [Tracheotomy and high-flow oxygen therapy for mechanical ventilation weaning].

PMID- 28502366
TI  - [Management of inpatients with acute COPD exacerbation. When to indicate
      mechanical ventilation?]

PMID- 28502367
TI  - [Antibiotics for acute exacerbation in hospitalized COPD patients].

PMID- 28502369
TI  - [Oxygen therapy for acute COPD exacerbations].

PMID- 28502368
TI  - [What is the role of non-inhaled drug management in acute COPD exacerbation?]

PMID- 28502370
TI  - [Differential diagnosis of acute COPD exacerbations].

PMID- 28502371
TI  - Decreased clinic visits for acute respiratory infections following an adult
      tonsillectomy: A population-based study.
AB  - PURPOSE: This study attempted to investigate the effects of a tonsillectomy on
      utilization of medical resources for acute respiratory infections by comparing
      numbers and costs of clinic visits within 1year before and after a tonsillectomy.
      MATERIALS AND METHODS: Data for this study were retrieved from the Taiwan
      Longitudinal Health Insurance Database 2005. The study includes 481 patients aged
      18-80years who underwent a tonsillectomy and 481 comparison patients. A
      multivariate regression model employing difference-in-difference was carried out
      to assess the independent association between a tonsillectomy and the number and
      costs of clinic visits. RESULTS: We found that for patients who underwent a
      tonsillectomy, the mean number of clinic visits for acute respiratory care 1year
      before and after the index date significantly decreased from 7.3 to 4.2
      (p<0.001). However, for the comparison group, there was no significant difference
      in the number (p=0.540) or costs (p=0.221) of clinic visits for acute respiratory
      care 1year before and after the index date. A multivariate regression model
      revealed that a tonsillectomy was associated with a reduction of 3.38 in the mean
      number of clinic visits for acute respiratory care (p<0.001). In other words, a
      tonsillectomy reduced by 46.3% (3.38/7.3) the number of clinic visits for acute
      respiratory care after adjusting for sociodemographic characteristics and medical
      comorbidities compared to comparison patients. CONCLUSIONS: This study
      demonstrated that a tonsillectomy was of substantial benefit to adult patients in
      that it provides decreased healthcare utilization for acute respiratory
      infections.

PMID- 28502373
TI  - [The oral cavity: A mirror of diabetes].
AB  - Diabetes and the oral cavity are closely associated as diabetes physiopathology
      affects the mouth and the oral manifestations are numerous and varied. These need
      to be searched systematically at every clinical examination as they are not only
      comorbidity factors but also have a two-way relationship with diabetes control.
      Periodontal diseases are the most frequent pathologies and the relationship with
      glycemic control has clearly been established: their frequency increases in case
      of uncontrolled glycemia, which makes them a good marker of glycated hemoglobin.
      Thorough oral health follow-up of diabetic patients that is coordinated by its
      various actors from the beginning of the treatment is thus of great interest.
      Most of the care given to diabetic patients can easily be performed at the dental
      clinic, provided adequate precautions are taken and improvement of the oral
      cavity is beneficial to glycemic control as well as to the patients' quality of
      life. When implemented by trained oral health professionals in dental clinics,
      therapeutic education proves highly efficient.

PMID- 28502376
TI  - [2016 European Society of Cardiology guidelines for the management of
      dyslipidemias].
AB  - Cardiovascular risk evaluation is a fundamental approach in cardiovascular
      prevention. Cardiovascular risk categories are associated with lipid-lowering
      drug intensity. LDL cholesterol is the main target of treatment. Statins are the
      first line lipid-lowering drugs. Lipid-lowering combination therapy is to be used
      in order to obtain the LDL cholesterol targets. Screening of familial
      hypercholesterolemia might be included in all prevention population strategy.

PMID- 28502374
TI  - [Severe membranoproliferative glomerulonephritis with polyadenopathy associated
      with hypocomplementemic urticarial vasculitis syndrome].

PMID- 28502372
TI  - Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or
      CTRC Gene Mutations.
AB  - OBJECTIVES: To assess whether the age of onset was associated with unique
      features or disease course in pediatric acute recurrent pancreatitis (ARP) or
      chronic pancreatitis (CP). STUDY DESIGN: Demographic and clinical information on
      children with ARP or CP was collected at INSPPIRE (INternational Study Group of
      Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend
      test and Jonckheere-Terpstra test were used to examine for differences between
      pediatric age groups (<6, 6-11, and >=12 years). RESULTS: Between September 2012
      and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6
      years of age at the time of first diagnosis of acute pancreatitis, 111 (32%) were
      6-11 years of age, and 102 (30%) were >=12 years of age. Early-onset disease was
      associated with mutations in cationic trypsinogen (PRSS1) (P < .01), chymotrypsin
      C (CTRC) (P = .01), family history of acute pancreatitis (P = .02), family
      history of CP (P < .01), biliary cysts (P = .04), or chronic renal failure (P =
      .02). Later-onset disease was more commonly present with hypertriglyceridemia (P
      = .04), ulcerative colitis (P = .02), autoimmune diseases (P < .0001), or
      medication use (P < .01). Children with later-onset disease also were more likely
      to visit the emergency department (P < .05) or have diabetes (P < .01).
      CONCLUSIONS: Early-onset pancreatitis is associated strongly with PRSS1 or CTRC
      mutations and family history of pancreatitis. Children with later-onset disease
      are more likely to have nongenetic risk factors. Future studies are needed to
      investigate whether the disease course, response to therapy, or clinical outcomes
      differ relative to the timing of disease onset.

PMID- 28502375
TI  - [Pyomyositis associated with reactive arthritis].

PMID- 28502377
TI  - Long-term follow-up of patients undergoing autologous noncultured melanocyte
      keratinocyte transplantation for vitiligo and other leukodermas.
AB  - BACKGROUND: Persistence of pigmentation after a melanocyte-keratinocyte
      transplantation procedure (MKTP) is an important consideration for efficacy.
      OBJECTIVE: We sought to determine long-term repigmentation of MKTP in vitiligo
      and other leukodermas. METHODS: A retrospective review of electronic medical
      records was conducted for all MKTPs performed at Henry Ford Hospital between
      January 2009 and April 2014. Repigmentation was assessed by a 5-point grading
      scale (poor to excellent) and Vitiligo Area Scoring Index (VASI). RESULTS: One
      hundred patients had MKTP performed at 236 anatomically-based lesions (ABLs); 63
      patients with 157 ABLs had long-term data available (12-72 months; median, 24
      months). Segmental vitiligo, nonsegmental vitiligo, and physical leukoderma
      demonstrated improvement in VASI scores: -75.6 +/- 24.6%, -59.2 +/- 36.6%, and 
      32.4 +/- 33.5%, respectively. In vitiligo, at 24, 48, and 72 months after MKTP,
      53%, 64%, and 53% of ABLs, respectively, maintained >75% repigmentation. Skin
      phototype, age, and anatomic location of ABLs had no significant effect on the
      outcome of treatment. LIMITATIONS: Limitations of the study include the
      retrospective design with uncontrolled, postoperative adjuvant treatments and
      inconsistent compliance to scheduled follow-up evaluations. CONCLUSIONS: MKTP
      provides satisfactory long-term repigmentation in the majority of appropriately
      selected patients with leukoderma. MKTP can maintain repigmentation for at least
      72 months.

PMID- 28502378
TI  - Long-term treatment of cutaneous manifestations of tuberous sclerosis complex
      with topical 1% sirolimus cream: A prospective study of 25 patients.
AB  - BACKGROUND: Data on long-term topical sirolimus treatment of the cutaneous
      manifestations of tuberous sclerosis complex are rare. OBJECTIVE: To evaluate the
      long-term benefit and tolerance of topical 1% sirolimus in tuberous sclerosis
      complex. METHODS: In this 18-month prospective single-center study, 1% sirolimus
      cream was applied daily to facial angiofibromas (FAs), fibrous cephalic plaques
      (FCPs), shagreen patches, hypomelanotic macules, and ungual fibromas. After
      complete clearance (CC) of FAs, we evaluated a maintenance protocol of 3
      applications weekly. RESULTS: Twenty-five patients were enrolled. Fifty percent
      obtained CC of FAs within 9 months. Of 7 patients with CC (58%) who were
      following the maintenance protocol, 6 relapsed within 7 months and 1 was still
      responding at 1 year. Of 16 patients with FCPs, 7 (44%) remained stable at 12
      months and 9 (56%) improved after 3 to 9 months of treatment. Only 1 of 5
      patients treated for shagreen patches showed improvement at 12 months. Treatment
      was well tolerated with no serious adverse events. LIMITATIONS: The small number
      of patients was a limitation. CONCLUSIONS: Topical 1% sirolimus applied daily
      produced positive responses in treatment of FAs, FCPs, and facial hypomelanotic
      macules and was well tolerated. A 3-times-weekly maintenance protocol did not
      prevent FA relapses.

PMID- 28502380
TI  - Author's reply to 'Letter to the Editor: Use of Almelo Hip Fracture Score to
      predict early mortality following hip fracture surgery'.

PMID- 28502379
TI  - External validation of the clinical indications of computed tomography (CT) of
      the head in patients with low-energy geriatric hip fractures.
AB  - INTRODUCTION: On evaluation of the clinical indications of computed tomography
      (CT) scan of head in the patients with low-energy geriatric hip fractures, Maniar
      et al. identified physical evidence of head injury, new onset confusion, and
      Glasgow Coma Scale (GCS)<15 as predictive risk factors for acute findings on CT
      scan. The goal of the present study was to validate these three criteria as
      predictive risk factors for a larger population in a wider geographical
      distribution. PATIENTS AND METHODS: Patients >=65 years of age with low-energy
      hip fractures from 6 trauma centers in a wide geographical distribution in the
      United States were included in this study. In addition to the relevant patient
      demographic findings, the above mentioned three criteria and acute findings on
      head CT scan were gathered as categorical variables. RESULTS: In total 799
      patients from 6 centers were included in the study. There were 67 patients (8.3%)
      with positive acute findings on head CT scan. All of these patients (100%) had at
      least one criteria positive. There were 732 patients who had negative acute
      findings on head CT scan with 376 patients (51%) having at least one criteria
      positive and 356 patients (49%) having no criteria positive. Sensitivity of 100%
      and negative predictive value of 100% was observed to predict negative acute
      findings on head CT scan when all the three criteria were negative. CONCLUSION:
      With the observed 100% sensitivity and 100% negative predictive value, physical
      evidence of acute head injury, acute retrograde amnesia, and GCS<15 can be
      recommended as a clinical decision guide for the selective use of head CT scans
      in geriatric patients with low energy hip fractures. All the patients with
      positive acute head CT findings can be predicted in the presence of at least one
      positive criterion. In addition, if these criteria are used as a pre-requisite to
      order the head CT, around 50% of the unnecessary head CT scans can be avoided.

PMID- 28502381
TI  - Linking lysosomal acid lipase insufficiency to the development of cryptogenic
      cirrhosis.

PMID- 28502382
TI  - Stochastic contraction based online estimation of second order wiener system.
AB  - Wiener system is a block oriented model, having a linear time-invariant dynamic
      system followed by a memory-less nonlinearity. To design a stochastic estimator
      for online estimation of Wiener system of second order, this paper utilizes
      differential mean value theorem and the results of stochastic contraction theory.
      The asymptotic convergence of proposed estimator is derived by using contraction
      theory related to semi-contracting systems. The boundedness and convergence of
      the parameter and state estimates have been shown analytically. The introduced
      method has potentials to estimate accurately states and parameters of Wiener
      model simultaneously from the noisy output of the system and unknown structure of
      nonlinearity. Numerical simulation of the stochastic estimator is presented to
      justify the claim by considering the two examples of the real world system with
      an additive measurement noise.

PMID- 28502383
TI  - Rolling bearing fault diagnosis using adaptive deep belief network with dual-tree
      complex wavelet packet.
AB  - Automatic and accurate identification of rolling bearing fault categories,
      especially for the fault severities and compound faults, is a challenge in
      rotating machinery fault diagnosis. For this purpose, a novel method called
      adaptive deep belief network (DBN) with dual-tree complex wavelet packet (DTCWPT)
      is developed in this paper. DTCWPT is used to preprocess the vibration signals to
      refine the fault characteristics information, and an original feature set is
      designed from each frequency-band signal of DTCWPT. An adaptive DBN is
      constructed to improve the convergence rate and identification accuracy with
      multiple stacked adaptive restricted Boltzmann machines (RBMs). The proposed
      method is applied to the fault diagnosis of rolling bearings. The results confirm
      that the proposed method is more effective than the existing methods.

PMID- 28502384
TI  - Sports science needs more interdisciplinary, constraints-led research programmes:
      The case of water safety in New Zealand.
AB  - In the lead article of this special issue, Paul Glazier proposes that Newell's
      constraints model has the potential to contribute to a grand unified theory of
      sports performance in that it can help to integrate the disciplinary silos that
      have typically operated in isolation in sports and exercise science. With a few
      caveats discussed in this commentary, we agree with Glazier's proposal. However,
      his ideas suggest that there is a need to demonstrate explicitly how such an
      integration might occur within applied scientific research. To help fill this
      perceived 'gap' and thereby illustrate the value of adopting a constraints-led
      approach, we offer an example of our own interdisciplinary research programme. We
      believe our research on water safety is ideally suited to this task due to the
      diverse range of interacting constraints present and as such provides a tangible
      example of how this approach can unify different disciplinary perspectives
      examining an important aspect of sport performance.

PMID- 28502386
TI  - ?

PMID- 28502385
TI  - The effects of blood glucose regulation on tear function tests in diabetic
      patients.
AB  - PURPOSE: To investigate whether blood glucose regulation in patients with
      diabetes mellitus (DM) has an influence on the ocular surface disease index
      (OSDI) score and tear function tests such as tear film osmolarity (TFO), tear
      break-up time (TBUT) and Schirmer tests. METHODS: Fifty diabetic patients with a
      fasting blood glucose (FBG) level greater than 200mg/dL and HbA1c level greater
      than 10% were recruited for this prospective study. All of the patients underwent
      a detailed ophthalmic examination including OSDI questionnaire, TFO test, TBUT
      test and Schirmer test initially. All tests were repeated after obtaining
      regulation of patients' blood sugar (approximately 6 weeks later). RESULTS: The
      mean age of the diabetic patients in the study was 54.96+/-12.48 years.
      Initially, the mean FBG, postprandial blood glucose (PBG) and HbA1c levels were
      301.40+/-79.11mg/dL, 431.06+/-74.47mg/dL and 12.31+/-1.67%, respectively. After
      blood glucose regulation; the levels of all parameters (153.78+/-59.32mg/dL,
      252.32+/-88.34mg/dL and 9.67+/-1.60%, respectively) statistically significantly
      decreased (P<0.001). The mean levels of OSDI score, TFO measurement, TBUT test
      and Schirmer test were 28.38+/-16.46 points, 349.66+/-13.09 mOsm/L, 6.44+/-1.91s
      and 8.66+/-3.57mm initially, and 17.82+/-11.70 points, 314.14+/-12.80 mOsm/L,
      6.62+/-2.03s and 9.02+/-3.68mm after blood glucose regulation, respectively.
      Although the improvements in TBUT and Schirmer test values were not statistically
      significant (P>0.05), statistically significant reduction was obtained in OSDI
      scores and TFO levels (P<0.001, for each). CONCLUSION: DM, which is a
      hyperosmolar disorder, appears to cause elevation in OSDI score and increase in
      TFO level, especially if blood glucose is poorly regulated.

PMID- 28502387
TI  - Anterolateral Ligament Reconstruction Techniques, Biomechanics, and Clinical
      Outcomes: A Systematic Review.
AB  - PURPOSE: To perform a systematic review of the described anterolateral ligament
      (ALL) reconstruction techniques, biomechanical performance, and clinical outcomes
      of ALL reconstruction in the setting of concurrent anterior cruciate ligament
      (ACL) reconstruction. METHODS: A systematic review was performed according to
      PRISMA guidelines using the Cochrane Database of Systematic Reviews, the Cochrane
      Central Register of Controlled Trials, PubMed, MEDLINE, and Embase, from 1980 to
      present. Inclusion criteria were as follows: ALL reconstruction techniques, ALL
      reconstruction biomechanical studies, ALL surgical outcomes, English language,
      human studies with at least 2 years of follow-up, and cadaveric studies.
      Exclusion criteria were lateral extra-articular tenodesis, ALL anatomic studies,
      ALL radiographic studies, animal studies, clinical studies with <2 years of
      follow-up, editorial articles, and surveys. RESULTS: The systematic review
      identified 12 articles that met the inclusion criteria: 6 techniques, 5
      biomechanical studies, and 1 outcome study were available. Five studies described
      ALL reconstruction in the setting of ACL reconstruction, whereas 1 study
      described isolated ALL reconstruction. Femoral tunnel location was most commonly
      placed posterior and proximal to the lateral epicondyle, whereas 2 studies
      reported a distal tunnel location. There was little variability in tibial tunnel
      location. The most common ALL reconstruction graft used was the gracilis tendon.
      Review of the biomechanical studies revealed internal rotation overconstraint
      with the posterior/proximal femoral tunnel position but not anterior/distal,
      although fixation angle and graft tension were inconsistent. Only 1 clinical
      study with 2 years' follow-up was available and reported improvement in the
      majority of cases. Complications occurred in 15 patients, including a residual
      pivot shift in 8% of patients at 2 years after a combined ACL and ALL
      reconstruction. CONCLUSIONS: There is inconsistency in the selection of ALL graft
      femoral attachment location as well as in the biomechanical performance of ALL
      reconstruction techniques. LEVEL OF EVIDENCE: Level IV, systematic review of
      Level IV studies.

PMID- 28502388
TI  - The Grapefruit: An Alternative Arthroscopic Tool Skill Platform.
AB  - PURPOSE: To establish the construct validity of an arthroscopic training model
      that teaches arthroscopic tool skills including triangulation, grasping,
      precision biting, implant delivery and ambidexterity and uses a whole grapefruit
      for its training platform. METHODS: For the grapefruit training model (GTM), an
      arthroscope and arthroscopic instruments were introduced through portals cut in
      the grapefruit skin of a whole prepared grapefruit. After institutional review
      board approval, participants performed a set of tasks inside the grapefruit.
      Performance for each component was assessed by recording errors, achievement of
      criteria, and time to completion. A total of 19 medical students, orthopaedic
      surgery residents, and fellowship-trained orthopaedic surgeons were included in
      the analysis and were divided into 3 groups based on arthroscopic experience. One
      way analysis of variance (ANOVA) and the post hoc Tukey test were used for
      statistical analysis. RESULTS: One-way ANOVA showed significant differences in
      both time to completion and errors between groups, F(2, 16) = 16.10, P < .001;
      F(2, 16) = 17.43, P < .001. Group A had a longer time to completion and more
      errors than group B (P = .025, P = .019), and group B had a longer time to
      completion and more errors than group C (P = .023, P = .018). CONCLUSIONS: The
      GTM is an easily assembled and an alternative arthroscopic training model that
      bridges the gap between box trainers, cadavers, and virtual reality simulators.
      Our findings suggest construct validity when evaluating its use for teaching the
      basic arthroscopic tool skills. As such, it is a useful addition to the
      arthroscopic training toolbox. CLINICAL RELEVANCE: There is a need for validated
      low-cost arthroscopic training models that are easily accessible.

PMID- 28502389
TI  - A Glitch in the Matrix: Aberrant Extracellular Matrix Proteolysis Contributes to
      Alcohol Seeking.

PMID- 28502390
TI  - Tipping the Scales Toward Addiction.

PMID- 28502392
TI  - Retraction.

PMID- 28502391
TI  - Bed Nucleus of the Stria Terminalis-Derived Corticotropin-Releasing Factor
      Controls Binge Alcohol Drinking Via Interacting With Corticotropin-Releasing
      Factor Receptors 1 and 2 in the Ventral Tegmental Area.

PMID- 28502393
TI  - As Hopes Have Flown Before: Toward the Rational Design of Treatments for Alcohol
      Use Disorder.

PMID- 28502394
TI  - Similitude in Methamphetamine-Induced Neuroadaptations Across Susceptibility and
      Chronic Drug Exposure Paradigms.

PMID- 28502395
TI  - Multicenter evaluation of the RAPIDEC(r) CARBA NP test for rapid screening of
      carbapenemase-producing Enterobacteriaceae and Gram-negative nonfermenters from
      clinical specimens.
AB  - The rapid diagnosis of carbapenemase-producing (CP) bacteria is essential for the
      management of therapy and infection control. In this study, RAPIDEC(r) CARBA NP
      (RCNP) was evaluated for the rapid screening of CP Enterobacteriaceae,
      Acinetobacter baumannii complex, and Pseudomonas aeruginosa from clinical
      specimens collected at five Italian hospitals. Firstly, each site tested 20 well
      characterized strains in a blinded fashion. Secondly, each center prospectively
      tested 25 isolates from blood cultures processed with a rapid workflow (6h after
      subculture) and 25 isolates from other specimens processed after an overnight
      culture. The presence of carbapenemases was confirmed by multiplex real-timePCRs
      targeting carbapenemase genes. RCNP presented an overall sensitivity,
      specificity, positive predictive value, and negative predictive value of 70%,
      94%, 82%, and 89%, respectively, with a higher performance in detection of CP
      Enterobacteriaceae and a poorer performance in detection of CP A. baumannii
      complex. With isolates from blood cultures, RCNP could significantly reduce the
      time required for identification of CP Enterobacteriaceae (less than 9h since the
      positivization of blood cultures).

PMID- 28502396
TI  - Comparative evaluation of 2 rapid immunochromatographic assays for Orientia
      tsutsugamushi in northeastern Thailand.

PMID- 28502397
TI  - Performance of the check-points check-MDR CT103XL assay utilizing the CDC/FDA
      antimicrobial resistance isolate bank.
AB  - The Check-MDR CT103XL beta-lactamase assay was validated for use in the clinical
      microbiology laboratory using two CDC-FDA Antimicrobial Resistant Isolate Bank
      panels (133 gram-negative bacilli known beta-lactamase genes). The CT103XL
      detected most reported resistance genes (123 of 136 genes) and additionally
      identified several resistance genes not reported by the CDC. Discrepant results
      were confirmed via whole genome sequencing.

PMID- 28502398
TI  - Correlations between individual susceptibility to visually induced motion
      sickness and decaying time constant of after-nystagmus.
AB  - This study examines the correlations between optokinetic after-nystagmus (OKAN)
      parameters and individual susceptibility to visually induced motion sickness
      (VIMS). Twenty-seven participants were exposed to vertical black-and-white
      stripes drifting along the yaw axis at 60 degrees  per second for 30 min to
      collect individual VIMS data (Phase 1). Two weeks after the exposure, OKANs were
      measured (Phase 2). 19 out of 27 participants (i.e., 70%) exhibited consistent
      OKAN patterns. Significant correlations between the time constants of OKAN and
      levels of VIMS experienced by the same viewers were found. Four months later,
      these 27 participants were invited back for a second OKAN measurement (Phase 3).
      Twenty-one participants came back. Their two OKAN measurements were significantly
      correlated (r = 0.69, p = 0.001). Rated levels of VIMS in phase 1 significantly
      correlated with the time constant of OKAN in both Phase 2 (r = 0.51, p = 0.044)
      and Phase 3 (r = 0.74, p = 0.006). The implications of the correlation results
      are discussed.

PMID- 28502399
TI  - User roles and contributions during the new product development process in
      collaborative innovation communities.
AB  - Collaborative innovation (co-innovation) community emerges as a new product
      design platform where companies involve users in the new product development
      (NPD) process. Large numbers of users participate and contribute to the process
      voluntarily. This exploratory study investigates the heterogeneous roles of users
      based on a global co-innovation project in online community. Content analysis,
      social network analysis and cluster method are employed to measure user
      behaviors, distinguish user roles, and analyze user contributions. The study
      identifies six user roles that emerge during the NPD process in co-innovation
      community: project leader, active designer, generalist, communicator, passive
      designer, and observer. The six user roles differ in their contribution forms and
      quality. This paper contributes to research on co-innovation in online
      communities, including design team structure, user roles and their contribution
      to design task and solution, as well as user value along the process. In
      addition, the study provides practices guidance on implementing project,
      attracting users, and designing platform for co-innovation community
      practitioners.

PMID- 28502400
TI  - Bags, batteries and boxes: A qualitative interview study to understand how
      syringe drivers are adapted and used by healthcare staff.
AB  - Syringe drivers are medical devices that are critical for end of life care. They
      deliver continuous medication over extended periods of time. Their design
      contributes to the quality of experience for both patients and healthcare
      professionals. Little research has been published about the factors that
      influence the usability of this type of equipment for frontline users (i.e. those
      in direct contact with patients) and how equipment gets introduced. Understanding
      how syringe drivers are used in practice can help improve the design of
      equipment. 27 semi-structured interviews were conducted across acute hospitals,
      community hospitals and hospices (4 organisations in total). All participating
      organisations used the same type of syringe driver. It was found that frontline
      staff needed to adapt this equipment to fit the circumstances of use. The
      analysis provided examples of this happening for aspects relating to the
      appearance of the device (bags), accessories (batteries) and security (the
      lockable box).

PMID- 28502401
TI  - Effect of local magnetic field disturbances on inertial measurement units
      accuracy.
AB  - Inertial measurement units (IMUs), a practical motion analysis technology for
      field acquisition, have magnetometers to improve segment orientation estimation.
      However, sensitivity to magnetic disturbances can affect their accuracy. The
      objective of this study was to determine the joint angles accuracy of IMUs under
      different timing of magnetic disturbances of various durations and to evaluate a
      few correction methods. Kinematics from 12 individuals were obtained
      simultaneously with an Xsens system where an Optotrak cluster acting as the
      reference system was affixed to each IMU. A handling task was executed under
      normal laboratory conditions and imposed magnetic disturbances. Joint angle RMSE
      was used to conduct a three-way repeated measures analysis of variance in order
      to contrast the following disturbance factors: duration (0, 30, 60, 120 and 240
      s), timing (during the disturbance, directly after it and a 30-second delay after
      it) and axis (X, Y and Z). The highest joint angle RMSE was observed on rotations
      about the Y longitudinal axis and during the longer disturbances. It stayed high
      directly after a disturbance, but returned close to baseline after a 30-second
      delay. When magnetic disturbances are experienced, waiting 30 s in a normal
      condition is recommended as a way to restore the IMUs' initial accuracy. The
      correction methods performed modestly or poorly in the reduction of joint angle
      RMSE.

PMID- 28502402
TI  - Decisionmaking in practice: The dynamics of muddling through.
AB  - An alternative to conventional models that treat decisions as open-loop
      independent choices is presented. The alterative model is based on observations
      of work situations such as healthcare, where decisionmaking is more typically a
      closed-loop, dynamic, problem-solving process. The article suggests five
      important distinctions between the processes assumed by conventional models and
      the reality of decisionmaking in practice. It is suggested that the logic of
      abduction in the form of an adaptive, muddling through process is more consistent
      with the realities of practice in domains such as healthcare. The practical
      implication is that the design goal should not be to improve consistency with
      normative models of rationality, but to tune the representations guiding the
      muddling process to increase functional perspicacity.

PMID- 28502403
TI  - The role of driver age in performance and attention allocation effects of roadway
      sign count, format and familiarity.
AB  - White-on-blue logo signs are used to inform drivers of food, gas, lodging, and
      attraction businesses at highway interchanges. In this study, 60 drivers were
      asked to look for food and attraction targets on logo signs while driving in a
      realistic freeway simulation. The objective of the study was to quantify effects
      of the number of sign panels (six vs. nine), logo familiarity (familiar vs.
      unfamiliar), logo format (text vs. pictorial), and driver age (young, middle, and
      elderly) on performance, attention allocation and target identification accuracy.
      Results revealed elderly drivers to exhibit worse performance in comparison to
      middle-age and young groups even though they adopted a more conservative driving
      strategy. There was no significant effect of the number of panels, logo
      familiarity, and logo format on driver performance or attention allocation. In
      target identification, drivers were more accurate with familiar or text-based
      panels appearing in six-panel signs.

PMID- 28502404
TI  - Application of classification principles to improve the reliability of incident
      classification systems: A test case using HFACS-ADF.
AB  - Accident classification systems are important tools for safety management.
      Unfortunately, many of the tools available have demonstrated poor reliability of
      coding, making their validity and usefulness questionable. This paper
      demonstrates the application of four strategies to improve the reliability of
      accident and incident classification systems. The strategies include creating a
      domain-specific system with limitations on system size and careful selection of
      codes, specifically the reduction of abstract concepts and bias-causing
      terminology. Using HFACS-ADF as a test case, the system was adapted using the
      strategies and validated using comprehension and comprehensiveness testing. The
      new system was then assessed for reliability. The reliability of the system
      increased by at least 20% at all levels of the classification system following
      the changes made. The results provide evidence that the application of
      theoretically and empirically-derived classification principles are effective for
      improving the reliability of accident and incident classification systems in high
      hazard industries.

PMID- 28502405
TI  - A practical guidance for assessments of sedentary behavior at work: A PEROSH
      initiative.
AB  - Sedentary behavior is defined as sitting or lying with low energy expenditure.
      Humans in industrialized societies spend an increasing amount of time in
      sedentary behaviors every day. This has been associated with detrimental health
      outcomes. Despite a growing interest in the health effects of sedentary behavior
      at work, associations remain unclear, plausibly due to poor and diverse methods
      for assessing sedentary behavior. Thus, good practice guidance for researchers
      and practitioners on how to assess occupational sedentary behavior are needed.
      The aim of this paper is to provide a practical guidance for practitioners and
      researchers on how to assess occupational sedentary behavior. Ambulatory systems
      for use in field applications (wearables) are a promising approach for sedentary
      behavior assessment. Many different small-size consumer wearables, with long
      battery life and high data storage capacity are commercially available today.
      However, no stand-alone commercial system is able to assess sedentary behavior in
      accordance with its definition. The present paper offers decision support for
      practitioners and researchers in selecting wearables and data collection
      strategies for their purpose of study on sedentary behavior. Valid and reliable
      assessment of occupational sedentary behavior is currently not easy. Several
      aspects need to be considered in the decision process on how to assess sedentary
      behavior. There is a need for development of a cheap and easily useable wearable
      for assessment of occupational sedentary behavior by researchers and
      practitioners.

PMID- 28502406
TI  - Steering the conversation: A linguistic exploration of natural language
      interactions with a digital assistant during simulated driving.
AB  - Given the proliferation of 'intelligent' and 'socially-aware' digital assistants
      embodying everyday mobile technology - and the undeniable logic that utilising
      voice-activated controls and interfaces in cars reduces the visual and manual
      distraction of interacting with in-vehicle devices - it appears inevitable that
      next generation vehicles will be embodied by digital assistants and utilise
      spoken language as a method of interaction. From a design perspective, defining
      the language and interaction style that a digital driving assistant should adopt
      is contingent on the role that they play within the social fabric and context in
      which they are situated. We therefore conducted a qualitative, Wizard-of-Oz study
      to explore how drivers might interact linguistically with a natural language
      digital driving assistant. Twenty-five participants drove for 10 min in a medium
      fidelity driving simulator while interacting with a state-of-the-art, high
      functioning, conversational digital driving assistant. All exchanges were
      transcribed and analysed using recognised linguistic techniques, such as
      discourse and conversation analysis, normally reserved for interpersonal
      investigation. Language usage patterns demonstrate that interactions with the
      digital assistant were fundamentally social in nature, with participants
      affording the assistant equal social status and high-level cognitive processing
      capability. For example, participants were polite, actively controlled turn
      taking during the conversation, and used back-channelling, fillers and
      hesitation, as they might in human communication. Furthermore, participants
      expected the digital assistant to understand and process complex requests
      mitigated with hedging words and expressions, and peppered with vague language
      and deictic references requiring shared contextual information and mutual
      understanding. Findings are presented in six themes which emerged during the
      analysis - formulating responses; turn-taking; back-channelling, fillers and
      hesitation; vague language; mitigating requests and politeness and praise. The
      results can be used to inform the design of future in-vehicle natural language
      systems, in particular to help manage the tension between designing for an
      engaging dialogue (important for technology acceptance) and designing for an
      effective dialogue (important to minimise distraction in a driving context).

PMID- 28502408
TI  - Combined effect of low back muscle fatigue and passive tissue elongation on the
      flexion-relaxation response.
AB  - Previous literature has documented the alterations in the flexion-relaxation
      response of the lumbar extensor musculature to passive tissue elongation (PTE)
      and muscle fatigue (MF). There is no study, however, that has explored this
      response as a function of the combined effect of both PTE and MF, which is often
      seen in occupational settings. Twelve participants performed three experimental
      protocols on three different days to achieve (1) PTE, (2) MF and (3) PTE&MF
      (combined). Trunk kinematics and muscle activities were monitored to assess the
      effects of these protocols on the peak lumbar flexion angle and the lumbar angle
      of the flexion-relaxation of the trunk extensor muscles. Results showed responses
      to the uni-dimensional stresses (PTE and MF) consistent with those seen in the
      previous literature, while the combined protocol elicited responses that more
      closely matched the PTE protocol.

PMID- 28502407
TI  - I spy with my little eye: Analysis of airline pilots' gaze patterns in a manual
      instrument flight scenario.
AB  - The aim of this study was to analyze pilots' visual scanning in a manual approach
      and landing scenario. Manual flying skills suffer from increasing use of
      automation. In addition, predominantly long-haul pilots with only a few
      opportunities to practice these skills experience this decline. Airline pilots
      representing different levels of practice (short-haul vs. long-haul) had to
      perform a manual raw data precision approach while their visual scanning was
      recorded by an eye-tracking device. The analysis of gaze patterns, which are
      based on predominant saccades, revealed one main group of saccades among long
      haul pilots. In contrast, short-haul pilots showed more balanced scanning using
      two different groups of saccades. Short-haul pilots generally demonstrated better
      manual flight performance and within this group, one type of scan pattern was
      found to facilitate the manual landing task more. Long-haul pilots tend to
      utilize visual scanning behaviors that are inappropriate for the manual ILS
      landing task. This lack of skills needs to be addressed by providing specific
      training and more practice.

PMID- 28502409
TI  - Field evaluation of a wearable multimodal soldier navigation system.
AB  - Challenging environments pose difficulties for terrain navigation, and therefore
      wearable and multimodal navigation systems have been proposed to overcome these
      difficulties. Few such navigation systems, however, have been evaluated in field
      conditions. We evaluated how a multimodal system can aid in navigating in a
      forest in the context of a military exercise. The system included a head-mounted
      display, headphones, and a tactile vibrating vest. Visual, auditory, and tactile
      modalities were tested and evaluated using unimodal, bimodal, and trimodal
      conditions. Questionnaires, interviews and observations were used to evaluate the
      advantages and disadvantages of each modality and their multimodal use. The
      guidance was considered easy to interpret and helpful in navigation. Simplicity
      of the displayed information was required, which was partially conflicting with
      the request for having both distance and directional information available.

PMID- 28502410
TI  - Performance awareness: Predicting cognitive performance during simulated
      shiftwork using chronobiological measures.
AB  - Physiological tracers of circadian rhythms and a performance awareness index were
      examined as predictors of cognitive performance during two sleep deprivation
      conditions common to occupational shiftwork. Study 1: Thirty-three sleep-deprived
      participants completed a simulated nightshift. Study 2: Thirty-two partially
      sleep-deprived participants completed a simulated dayshift. A standardized logic
      test was used to measure cognitive performance. Body temperature and heart rate
      were measured as chronobiological indices of endogenous circadian rhythms.
      Performance awareness was calculated as a correlation between actual and
      perceived performance. These studies demonstrated a parallelism between
      performance awareness and the circadian rhythm. Chronobiological changes were
      predictive of performance awareness during the simulated nightshift but not
      dayshift. Only oral temperature was a significant independent predictor. Oral
      temperature predicted an individual's awareness of their own performance better
      than their own subjective awareness. These findings suggest that using circadian
      rhythms in applied ergonomics may reduce occupational risk due to low performance
      awareness.

PMID- 28502411
TI  - Abdominal bracing during lifting alters trunk muscle activity and body
      kinematics.
AB  - We assessed whether participants are able to perform abdominal bracing during
      lifting, and described its effects on trunk muscle activity and body kinematics.
      Fourteen participants performed 10 lifts (symmetrical lifting of a 15 kg load
      from floor level), 5 with abdominal bracing and 5 without. Activity of the lumbar
      multifidus (LM) and internal oblique (IO) muscles, and trunk and lower body
      kinematics were obtained. During non-bracing lifting, IO activity did not
      increase beyond rested standing levels (with average muscle activity ranging
      between 8.2 and 9.1% maximum voluntary contraction; %MVC), while LM activity did
      (range: 8.5-21.0 %MVC). During bracing lifting, muscle activity was higher
      compared to non-bracing in IO and LM at the start of the lift (with average
      between condition differences up to 10.9 %MVC). Upper leg, pelvis and lumbar
      spine angles were smaller, but thorax flexion angles were larger while lifting
      with bracing compared to without (with average between condition differences
      ranging from 0.7 degrees  to 4.3 degrees ). Although participants do not
      typically brace their abdominal muscles while lifting, they can be trained to do
      so. There appears to be no clear advantage of abdominal bracing during lifting,
      leaving its value for low-back pain prevention unclear.

PMID- 28502412
TI  - Computer-based estimation of the hip joint reaction force and hip flexion angle
      in three different sitting configurations.
AB  - Sitting is part of our daily work and leisure activities and can be performed in
      different configurations. To date, the impact of different sitting configurations
      on hip joint loading has not been studied. We therefore evaluated the hip joint
      reaction force (HJRF) and hip flexion angle in a virtual representative male
      Caucasian population by means of musculoskeletal modelling of three distinct
      sitting configurations: a simple chair, a car seat and a kneeling chair
      configuration. The observed median HJRF in relation to body weight and hip
      flexion angle, respectively, was 22.3% body weight (%BW) and 63 degrees  for the
      simple chair, 22.5%BW and 79 degrees  for the car seat and 8.7%BW and 50 degrees 
      for the kneeling chair. Even though the absolute values of HJRF are low compared
      to the forces generated during dynamic activities, a relative reduction of over
      50% in HJRF was observed in the kneeling chair configuration. Second, the hip
      flexion angles were both in the kneeling chair (-29 degrees ) and simple chair
      configuration (-16 degrees ) lower compared to the car seat and, as such, did not
      reach the threshold value for femoroacetabular conflict. In conclusion, the
      kneeling chair appears to hold the greatest potential as an ergonomic sitting
      configuration for the hip joint.

PMID- 28502413
TI  - Understanding the determinants of health-related quality of life in rheumatoid
      arthritis-associated interstitial lung disease.
AB  - RATIONALE: Health-related quality of life (HRQL) is impaired among patients with
      interstitial lung disease (ILD). Little is understood about HRQL in specific
      subtypes of ILD. OBJECTIVES: The aim of this study was to characterize and
      identify clinical determinants of HRQL among patients with rheumatoid arthritis
      associated interstitial lung disease (RA-ILD) and compare them to patients with
      idiopathic pulmonary fibrosis (IPF). METHODS: We identified patients with a
      diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients.
      HRQL was measured at their baseline visit using the Short Form Health Survey (SF
      36), versions 1 and 2. Regression models were used to characterize and understand
      the relationship between selected baseline clinical covariates, the physical
      component score (PCS) and mental component score (MCS) of the SF-36. MEASUREMENTS
      AND MAIN RESULTS: RA-ILD patients (n = 50) were more likely to be younger and
      female compared to IPF patients (n = 50). After controlling for age and pulmonary
      function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured
      by the PCS (P = 0.03), with significant differences in two of four PCS domains -
      bodily pain (P < 0.01) and general health (P = 0.01). Clinical covariates most
      strongly associated with a lower PCS in RA-ILD patients compared to IPF patients
      were the presence of joint pain or stiffness and dyspnea severity (P < 0.01).
      Mental and emotional health, as measured by the MCS, was similar between RA-ILD
      and IPF patients. CONCLUSION: The physical components of HRQL appear worse in RA
      ILD patients compared to IPF patients as measured by the PCS of the SF-36.
      Differences in the PCS of the SF-36 can be explained in part by dyspnea severity
      and joint symptoms among patients with RA-ILD.

PMID- 28502415
TI  - Effects of acute psychological stress induced in laboratory on physiological
      responses in asthma populations: A systematic review.
AB  - BACKGROUND: Psychological stress has long been suspected to have a deleterious
      effect on asthma, with acute psychological stress being associated with
      physiological responses in asthma patients. OBJECTIVES: The purpose of this
      systematic review was to provide a narrative synthesis of the impact of acute
      laboratory psychological stress on physiological responses among asthma patients.
      METHODS: An extensive search was conducted by two independent authors using
      Pubmed, PsycINFO, PsyArticles and the Cochrane Library electronic databases (up
      to September 2016). English and French articles which assessed physiological
      responses during or post-stress and compare them to baseline or pre-stress values
      were included. RESULTS: Thirty-two studies met the inclusion criteria. Studies
      indicated that exposure to active stressors (e.g., arithmetic tasks) was
      associated with an increase in sympathetic nervous system (SNS) responses,
      cortisol, and inflammatory responses, but had little effect on the caliber of the
      bronchi. Exposure to passive stressors (e.g., watching stressful movies or
      pictures) was also associated with an increase in SNS responses and with mild
      bronchoconstriction. However, a paucity of data for passive stressors limited
      conclusions on other measures. CONCLUSIONS: In patients with asthma, both active
      and passive stressors seem to be associated with an increased activation of the
      SNS. Passive stressors seem to have a more immediate, deleterious impact on the
      airways than active stressors, but the latter may be associated with delayed
      inflammatory driven an asthma exacerbation. Further studies are needed to
      understand the impact of acute stressors on the physiological mechanisms
      associated with asthma, particularly HPA and immune markers. Systematic review
      registration number: CRD42015026431.

PMID- 28502414
TI  - Acute bronchodilator responses to beta2-agonist and anticholinergic agent in
      COPD: Their different associations with exacerbation.
AB  - BACKGROUND: Acute bronchodilator response (BDR) is a potential phenotypic
      characteristic of COPD. However, the clinical factors associated with BDR in
      patients with COPD remain unclear, particularly for BDR to anticholinergic
      agents. OBJECTIVES: We aimed to clarify the clinical factors associated with BDR
      to beta2-agonist and/or anticholinergic agent, considering time-associated
      variations of BDR. We also evaluated the association between BDR and clinical
      course of COPD. METHODS: We analyzed 152 subjects who participated in the
      Hokkaido COPD cohort study. We repeatedly measured BDR to salbutamol (400 MUg) or
      oxitropium (400 MUg) three times for each every 6 months alternately over 3
      years. Reversibility was defined by >= 12% and >=200 mL increase in FEV1 over
      baseline. All subjects were classified into three groups based on the BDR
      stability; consistently reversible, consistently irreversible, and inconsistent.
      We compared baseline clinical characteristics and the 5-year clinical course of
      COPD among the three groups. RESULTS: For either agent, the mean blood eosinophil
      count was significantly higher in those with consistently reversible than those
      with consistently irreversible (p < 0.05). The subjects with consistently
      reversible to oxitropium (p < 0.05), but not to salbutamol (p = 0.56), showed
      increased risk of exacerbation compared with the other two groups. CONCLUSION: We
      identified the distinct clinical characteristics of COPD associated with acute
      BDR status. Increased cholinergic airway tone, which is reflected in the higher
      BDR only to anticholinergic agent, but not to beta2-agonist, may be associated
      with exacerbation in COPD.

PMID- 28502416
TI  - The heterogeneity of systemic inflammation in bronchiectasis.
AB  - BACKGROUND: Systemic inflammation in bronchiectasis is poorly studied in relation
      to aetiology and severity. We hypothesized that molecular patterns of
      inflammation may define particular aetiology and severity groups in
      bronchiectasis. METHOD: We assayed blood concentrations of 31 proteins from 90
      bronchiectasis patients (derivation cohort) and conducted PCA to examine
      relationships between these markers, disease aetiology and severity. Key results
      were validated in two separate cohorts of 97 and 79 patients from other centres.
      RESULTS: There was significant heterogeneity in protein concentrations across the
      derivation population. Increasing severity of bronchiectasis (BSI) was associated
      with increasing fibrinogen (rho = 0.34, p = 0.001 -validated in a second cohort),
      and higher fibrinogen was associated with worse lung function, Pseudomonas
      colonisation and impaired health-status. There were generally similar patterns of
      inflammation in patients with idiopathic and post-infectious disease. However,
      patients with primary immunodeficiency had exaggerated IL-17 responses, validated
      in a second cohort (n = 79, immunodeficient 12.82 pg/ml versus idiopathic/post
      infectious 4.95 pg/ml, p = 0.001), and thus IL-17 discriminated primary
      immunodeficiency from other aetiologies (AUC 0.769 (95%CI 0.661-0.877)).
      CONCLUSION: Bronchiectasis is associated with heterogeneity of systemic
      inflammatory proteins not adequately explained by differences in disease
      aetiology or severity. More severe disease is associated with enhanced acute
      phase responses. Plasma fibrinogen was associated with bronchiectasis severity in
      two cohorts, Pseudomonas colonisation and health status, and offers potential as
      a useful biomarker.

PMID- 28502417
TI  - Analysis of bronchial biopsies in chronic cough.
AB  - BACKGROUND: Chronic cough is commonly associated with asthma, gastro-oesophageal
      reflux disease and postnasal drip, but in a significant proportion, no associated
      cause can be found. We determined whether examination of bronchial biopsies would
      be useful in determining the cause associated with chronic cough. METHODS: 100
      consecutive patients referred to a specialist cough clinic underwent a systematic
      assessment including a fiberoptic bronchoscopy for bronchial biopsies. RESULTS:
      In 38 patients, treatment of associated causes led to amelioration of cough
      ('explained') and in 62, there was no association or improvement ('idiopathic').
      The latter group had a longer duration of cough, a lower FeNO levels and a more
      sensitive capsaicin cough response, with an increase in basement membrane
      thickness with no differences in goblet cell hyperplasia and seromucinous
      hyperplasia, and in lymphocyte, neutrophil and eosinophil counts. The duration of
      cough was inversely correlated with the degree of neutrophil infiltration.
      CONCLUSION: We conclude that pathological examination of bronchial biopsies is
      unlikely to be useful in the diagnosis of chronic cough in non-smokers.

PMID- 28502418
TI  - A multicenter, cross-sectional, observational study of budesonide/formoterol
      maintenance and reliever therapy in real-world settings.
AB  - BACKGROUND: To assess the level of asthma control achieved with
      budesonide/formoterol in Chinese patients with asthma, based on the Global
      Initiative for Asthma (GINA) definition and Asthma Control Test (ACT) score.
      METHODS: This multicenter, cross-sectional study (NCT01785901) evaluated asthma
      control levels in Chinese patients receiving physician-prescribed
      budesonide/formoterol treatment. Adults with a diagnosis of asthma >=6 months and
      receiving budesonide/formoterol treatment >=3 months before screening were
      consecutively enrolled. Data including medical and medication history were
      collected using face-to-face questionnaires and physical examinations during a
      single visit. RESULTS: A total of 1483 asthma out-patients from 27 medical
      centers were enrolled; 217 (14.6%) were treated with budesonide/formoterol using
      a fixed-dose strategy and 1266 (85.4%) with the SMART (Symbicort(r) Maintenance
      And Reliever Therapy) strategy. According to GINA criteria, asthma was controlled
      in 58.6% (95% CI: 56.1%-61.1%) of patients and was either controlled or partly
      controlled in 94.1% (95% CI: 92.8%-95.3%) of patients. According to ACT score,
      asthma was completely controlled in 22.4% (95% CI: 20.3%-24.6%) of patients and
      was either completely or well controlled in 83.3% (95% CI: 81.4%-85.2%) of
      patients. Multivariate logistic regression analysis revealed that a >5-year
      history of asthma and an age of >50 years were factors associated with lower
      levels of asthma control. CONCLUSIONS: This study demonstrated high levels of
      asthma control (GINA: controlled and partly controlled and ACT: completely and
      well controlled) in Chinese patients with asthma treated with
      budesonide/formoterol. Greater age and a longer disease history were associated
      with lower levels of asthma control. TRIAL REGISTRATION:
      ClinicalTrials.govNCT01785901. Registered February 5, 2013.

PMID- 28502420
TI  - Cardiopulmonary exercise testing and second-line pulmonary function tests to
      detect obstructive pattern in symptomatic smokers with borderline spirometry.
AB  - BACKGROUND: The need for additional research on symptomatic smokers with normal
      spirometry has been recently emphasized. Albeit not meeting criteria for Chronic
      obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may
      experience activity limitation, evidence of airway disease, and exacerbations.
      We, therefore, evaluated whether symptomatic smokers with borderline spirometry
      (post-bronchodilator FEV1/FVC ratio between 5th to 20th percentile of predicted
      values) have pulmonary function abnormalities at rest and ventilatory constraints
      during exercise. METHODS: 48 subjects (aged 60 +/- 8 years, mean +/- SD, 73%
      males, 16 healthy, and 17 symptomatic smokers) underwent cardiopulmonary exercise
      testing (CPET), body plethysmography, nitrogen single-breath washout test
      (N2SBW), lung diffusion for carbon monoxide (DLCO), and forced oscillation
      technique (FOT). RESULTS: Compared to healthy subjects, symptomatic smokers
      showed: 1) reduced breathing reserve (36 +/- 17 vs. 49 +/- 12%, P = 0.050); 2)
      exercise induced dynamic hyperinflation (-0.20 +/- 0.17 vs. -0.03 +/- 0.21 L, P =
      0.043); 3) higher residual volume (158 +/- 22 vs. 112 +/- 22%, P < 0.001); 4)
      phase 3 slope at N2SBW (4.7 +/- 2.1 vs. 1.4 +/- 0.6%, P < 0.001); 5) no
      significant differences in DLCO and FOT results. CONCLUSIONS: In smokers with
      borderline spirometry, CPET and second-line pulmonary function tests may detect
      obstructive pattern. These subjects should be referred for second line testing,
      to obtain a diagnosis, or at least to clarify the mechanisms underlying symptoms.
      Whether the natural history of these patients is similar to COPD, and they
      deserve a similar therapeutic approach is worth investigating.

PMID- 28502421
TI  - Is neoadjuvant chemoradiotherapy always necessary for mid/high local advanced
      rectal cancer: A comparative analysis after propensity score matching.
AB  - AIM: This study was aimed to compare perioperative and oncological outcomes of
      mid/high locally advanced midrectal cancer (LARC) treated with neoadjuvant
      chemoradiotherapy (NCRT) vs. surgery alone, and to identify risk factors for
      local recurrence in mid/high LARC. METHOD: A total of 471 mid/high LARC patients
      treated with surgery alone or NCRT (50.4 Gy in 28 fractions) with concurrent
      FOLFOX/XELOX followed by TME in 6-8 weeks from 2008 to 2014 were matched 1:1 by
      using propensity score analysis. Perioperative and survival outcome was compared
      between groups. Multivariate analyze was performed to identify risk factors for
      local recurrence. RESULTS: Two hundred and two patients were matched for the
      analysis. Postoperative morbidity was similar between groups. With a mean follow
      up of 57 months, the 5-year overall survival (NCRT vs. surgery alone: 80.4% vs.
      81.4%; p = 0.978), 5-year local recurrence rates (3.1% vs. 5%; p = 0.467), and 5
      year distant metastasis rates (29.5% vs. 23.7%; p = 0.140) were similar between
      two groups. Cox regression analysis showed that the circumferential resection
      margin (CRM) involvement (OR = 5.205, p = 0.005) was the only risk factor for
      local recurrence in mid/high LARC patients. CONCLUSION: In matched cohorts of
      mid/high LARC patients, surgery alone provided comparable oncological outcome,
      when compared with NCRT. CRM involvement was the only risk factor for local
      recurrence in mid/high rectal cancer. NCRT may not be always needed in mid/high
      LARC. A threatened CRM could be diagnosed up front and prevented by selecting CRT
      for these patients.

PMID- 28502422
TI  - Preimplantation genetic diagnosis for monogenic diseases.
AB  - Preimplantation genetic diagnosis (PGD) was first reported in 1990. Thereafter,
      more and more indications for PGD, including monogenic diseases (MGD) and
      translocations, are presently available, and the list of indications of PGD is
      expanding from early-onset and serious conditions to late-onset diseases.
      Polymerase chain reaction has been used for PGD of MGD, while newer techniques,
      including karyomapping and next-generation sequencing, emerge in recent decade.
      The limitations of various methods for PGD are discussed in this review.

PMID- 28502419
TI  - The performance of the GAP model in patients with rheumatoid arthritis associated
      interstitial lung disease.
AB  - BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is
      associated with significant morbidity and mortality. Similarities have been
      observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP
      (usual interstitial pneumonia) form of RA-ILD. The GAP (gender, age, physiology)
      model has been shown to predict mortality in patients with IPF, but its ability
      to predict mortality in RA-ILD is not known. METHODS: We identified 309 patients
      with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients
      with ILD. The primary endpoint was mortality. To handle missing data (n = 219
      subjects with complete dataset), multiple imputation by iterative chained
      equations was used. Using the GAP model as a baseline, we assessed improvements
      in mortality risk prediction achieved by incorporating additional variables.
      Model discrimination was assessed using the c-index, and calibration was checked
      by comparing observed and expected incidence of death. RESULTS: Patients had a
      mean age of 65 years and were predominantly female (54%). The mean forced vital
      capacity (FVC) % predicted was 73 and the mean diffusing capacity for carbon
      monoxide (DLCO) % predicted was 55. Twenty-four percent of the 236 patients with
      a high-resolution computed tomography scan available for review had a definite
      UIP pattern. The original GAP model, including gender, age, FVC%, and DLCO%, had
      a c-index of 0.746 in our cohort. Calibration of this model was satisfactory at
      1, 2 and 3 years. Model discrimination was not meaningfully improved by adding
      other clinical variables. CONCLUSION: The GAP model that was derived for IPF
      performs similarly as a mortality risk prediction tool in RA-ILD.

PMID- 28502423
TI  - Advanced functional materials in solid phase extraction for ICP-MS determination
      of trace elements and their species - A review.
AB  - For the determination of trace elements and their species in various real samples
      by inductively coupled plasma mass spectrometry (ICP-MS), solid phase extraction
      (SPE) is a commonly used sample pretreatment technique to remove complex matrix,
      pre-concentrate target analytes and make the samples suitable for subsequent
      sample introduction and measurements. The sensitivity, selectivity/anti
      interference ability, sample throughput and application potential of the
      methodology of SPE-ICP-MS are greatly dependent on SPE adsorbents. This article
      presents a general overview of the use of advanced functional materials (AFMs) in
      SPE for ICP-MS determination of trace elements and their species in the past
      decade. Herein the AFMs refer to the materials featuring with high adsorption
      capacity, good selectivity, fast adsorption/desorption dynamics and satisfying
      special requirements in real sample analysis, including nanometer-sized
      materials, porous materials, ion imprinting polymers, restricted access materials
      and magnetic materials. Carbon/silica/metal/metal oxide nanometer-sized
      adsorbents with high surface area and plenty of adsorption sites exhibit high
      adsorption capacity, and porous adsorbents would provide more adsorption sites
      and faster adsorption dynamics. The selectivity of the materials for target
      elements/species can be improved by using physical/chemical modification, ion
      imprinting and restricted accessed technique. Magnetic adsorbents in conventional
      batch operation offer unique magnetic response and high surface area-volume ratio
      which provide a very easy phase separation, greater extraction capacity and
      efficiency over conventional adsorbents, and chip-based magnetic SPE provides a
      versatile platform for special requirement (e.g. cell analysis). The performance
      of these adsorbents for the determination of trace elements and their species in
      different matrices by ICP-MS is discussed in detail, along with perspectives and
      possible challenges in the future development.

PMID- 28502424
TI  - Redox speciation of iron, manganese, and copper in cerebrospinal fluid by strong
      cation exchange chromatography - sector field inductively coupled plasma mass
      spectrometry.
AB  - A new method of simultaneous redox speciation of iron (II/III), manganese
      (II/III), and copper (I/II) in cerebrospinal fluid (CSF) has been designed. For
      the separation of redox species strong cation exchange chromatography (SCX) with
      isocratic elution was employed. Species were detected using inductively coupled
      plasma sector field mass spectrometry (ICP-sf-MS), operating at medium
      resolution. The following parameters were optimized: analytical column, eluent
      composition and pH, CSF injection volume and dilution factor. Analytical column
      Dionex IonPac CS5A RFIC 4*250 mm was found to retain and separate species of
      interest the most effectively under the isocratic elution with a buffer,
      containing 50 mM ammonium citrate, 7.0 mM pyridine-2,6-dicarboxylic acid at pH =
      4.2 and flow rate of 0.8 L min-1. Injection volume of 50 MUL with CSF sample
      dilution of 1/3 (v/v) with the eluent was shown to result in minimal matrix
      suppression. For species identification, retention time matching with standards
      was used. The stability of metalloproteins (ferritin, transferrin, and
      ceruloplasmin) under elution conditions was evaluated. For the quantification of
      redox species, external calibration was employed. To avoid column contamination,
      a blank was run after measurement and all quantification values were blank
      subtracted. For recovery checks, species quantification data was verified against
      total content of an element, measured by dynamic reaction cell ICP-MS. Recoveries
      (sum of quantified species vs. total element determinations) were 82.5 +/- 22%
      (Mn), 92 +/- 11% (Fe), and 88.7 +/- 12% (Cu). The method was tested using 38 real
      CSF samples. Limits of detection (3sigma) for the CSF samples were 0.5 MUg L-1,
      0.6 MUg L-1, and 0.8 MUg L-1 for Fe, Mn, and Cu species, respectively. Retention
      time precision was 1-7.5% (as RSD), whereas peak area RSDs were in the range 5
      11%, both depending on the species.

PMID- 28502425
TI  - Resonance energy transfer based electrochemiluminescence and fluorescence sensing
      of riboflavin using graphitic carbon nitride quantum dots.
AB  - Graphitic carbon nitride quantum dots (g-CNQDs) are rarely used in the field of
      electrochemiluminescence. In this paper, g-CNQDs have a strong and stable
      electrochemiluminescence (ECL) signal generated in the presence of co-reactant
      K2S2O8. The ECL signal of g-CNQDs was quenched by the mechanism of resonance
      energy transfer (RET) between donor g-CNQDs and receptor riboflavin (RF) that is
      proved by UV-vis absorption spectroscopy, electrochemiluminescence and
      fluorescence emission spectroscopy analysis technology. Therefore, we achieved
      detection of the riboflavin content in the drug tablets of vitamin B2 using ECL
      and FL. The determination results of ECL showed that the riboflavin content of
      the drug vitamin B2 (VB2) tablets was consistent with the fluorescence (FL)
      analysis, with wider linear range of 0.02-11 MUM and lower minimum detection
      limit of 0.63 nM (S/N = 3) than FL. Hence, the riboflavin content in human serum
      was further detected using ECL. The relative standard deviation is less than
      6.5%, with an acceptable recovery of 95.33%-104.22%, which means that this sensor
      has potential applications in the actual sample analysis. As a new ECL luminary,
      g-CNQDs have opened a new field for the development and application of ECL
      sensor.

PMID- 28502427
TI  - Metal-organic aerogel as a coating for solid-phase microextraction.
AB  - An iron-based metal-organic aerogel was synthesized using metal-organic framework
      nanoparticles and applied as a fiber coating for solid-phase microextraction
      (SPME). Chemical, thermal and morphological characteristics of the material were
      investigated. Headspace SPME followed by gas chromatography-electron capture
      detection was used for the determination of chlorobenzenes in the environmental
      samples. The key experimental factors affecting the extraction efficiency of the
      analytes, such as ionic strength, extraction and desorption temperature, and
      extraction time were investigated and optimized. The applicability of the coating
      for the extraction of chlorobenzenes from the environmental samples including
      river and tap water, sludge, and coastal soil was evaluated. The detection limits
      were in the range of 0.1-60 ng L-1. The relative standard deviations were between
      2.0 and 5.0%. The extraction recovery of the analytes was in the range of 88
      100%. Compared to the commercial PDMS fiber, the present fiber showed better
      extraction efficiency.

PMID- 28502426
TI  - Construction and optimization of an efficient breathing-based isothermal emulsion
      amplification method.
AB  - The reaction temperature is one of the main factors that affect the stability of
      emulsion PCR (emPCR). Focusing on this point, we applied the "DNA breathing"
      mechanism in BEAMing (Bead, Emulsion, Amplification, and Magnetic) and proposed a
      more stable emulsion amplification method. Compared to the conventional emPCR,
      this method provided excellent results. Firstly, more stable emulsion system
      resulted in higher percentage of single-molecular amplifications (73.17%).
      Secondly, an ordinary temperature-controlling device was enough. Our outcome
      showed that the reaction temperature of this method was not strict so that the
      ordinary temperature-controlling device was enough for it (the heat block sets
      vs. the PCR instrument: 13.140 +/- 0.110 vs. 13.008 +/- 0.039, P = 0.120).
      Thirdly, the single-biotinylated emP1 coated streptavidin beads were stable
      enough to be used for this method (the control temperature vs. the reaction
      temperature: 2967.91 +/- 409.045 vs. 3026.22 +/- 442.129, P = 0.334), which could
      replace the double-biotinylated emP1 coated beads and was benefit for saving
      cost. In conclusion, the method presented here with stable emulsion system,
      simplified temperature-controlling device, and decreased investment would be a
      highly streamlined and inexpensive option for future single-molecular
      amplification based researches.

PMID- 28502429
TI  - Quantification of monohydroxylated polycyclic aromatic hydrocarbons in human
      urine samples using solid-phase microextraction coupled with glass-capillary
      nanoelectrospray ionization mass spectrometry.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants with
      carcinogenic effect raising worldwide concerns. Hydroxylated PAHs (OH-PAHs) could
      be formed in the body as metabolites of PAHs in human urine samples and thus
      considered as biomarkers of PAH exposure. In this study, five OH-PAHs including 3
      phenanthrol, 1-naphthol, 2-hydroxy fluorene, 1-hydroxprene and 6-hydroxy chrysene
      in human urine samples were selectively enriched by C18 solid-phase
      microextraction (SPME), then SPME fiber was connected high voltage and then was
      inserted into a glass-capillary to elute and ionize the analytes for mass
      spectrometric (MS) detection. The coupling of SPME-MS showed excellent analytical
      performance for detection of urinary OH-PAHs under optimal conditions, providing
      an easy operation for rapid detection of a single sample within minutes. By use
      of internal standard (i.e., 2-hydroxy fluorene-d9), the limit of detection (LOD)
      and limit of quantitation (LOQ) of OH-PAHs were found to be less than 0.05 ng L-1
      level (S/N > 3) and less than 0.1 ng L-1 level (S/N > 10), respectively. The
      dynamic ranges of five OH-PAHs were found to be a range at 0.1-5.0 ng L-1 with
      excellent coefficient (R2 > 0.99). This method also showed good precisions (intra
      day: 3.4-5.5%, inter-day: 7.0-9.8%, n = 5) and good accuracy (85.3-95.3%, n = 5).
      Moreover, ion suppression and matrix effect in detection of OH-PAHs in urine were
      also investigated. Human urine samples collected from 12 volunteers including 6
      non-smokers and 6 smokers have been successfully analyzed, it was found that
      individual OH-PAHs in smokers were higher than in non-smokers. This study
      demonstrated that SPME coupled with glass-capillary nanoESI-MS is a sensitive
      method for rapid detection of urinary OH-PAHs for health risk assessment of PAHs
      exposure.

PMID- 28502428
TI  - Non-proximate mass spectrometry using a heated 1-m long PTFE tube and an air
      tight APCI ion source.
AB  - Direct and rapid trace-level gas analysis is highly needed in various fields such
      as safety and security, quality control, food analysis, and forensic medicine. In
      many cases, the real samples are bulky and are not accessible to the space
      limited ion source of the mass spectrometer. In order to circumvent this problem,
      we developed an airtight atmospheric-pressure chemical ionization (APCI) ion
      source equipped with a flexible 1-m-long, 2-mm-i.d. PTFE sniffing tube. The
      ambient air bearing sample gas was sucked into the heated PTFE tube (130  degrees
      C) and was transported to the air-tight ion source without using any extra
      pumping system or a Venturi device. Analytes were ionized by an ac corona
      discharge located at 1.5 mm from the inlet of the mass spectrometer. By using the
      airtight ion source, all the ionized gas in the ion source was introduced into
      the vacuum of the mass spectrometer via only the evacuation of the mass
      spectrometer (1.6 l min-1). Sub-pg limits of detection were obtained for carbaryl
      and trinitrotoluene. Owing to its flexibility and high sensitivity, the sniffing
      tube coupled with a mass spectrometer can be used as the stethoscope for the high
      sensitive gas analysis. The experimental results obtained for drugs, hydrogen
      peroxide and small alkanes were discussed by DFT calculations.

PMID- 28502430
TI  - Screening of unapproved drugs using portable Raman spectroscopy.
AB  - We present a four-step screening approach for unapproved drugs. The screening
      approach is both qualitative and quantitative in design in order to determine if
      the sample under study contains the correct and acceptable amount of the declared
      active pharmaceutical ingredient. Four commercially-available unapproved
      antibiotic and antiviral drugs were used in this study. Out of the 40 individual
      samples tested, 100% of the samples matched for the declared active
      pharmaceutical ingredient with no false positives. Following this qualitative
      identification step, a quantitative assay was used to determine the potency of
      the product. The assay involves dissolving the sample in water and using a
      partial least squares model to predict the potency of the product. The average
      Raman potency results for the four products tested were compared with
      chromatographic reference methods and the spectroscopic data were found to be
      within ~1-6% of those obtained with the reference method for the four products
      tested. The results indicate that aqueous-based Raman assays may be a suitable
      field-deployable alternative to traditional techniques run in a laboratory
      environment.

PMID- 28502431
TI  - A novel photoelectrochemical immunosensor by integration of nanobody and ZnO
      nanorods for sensitive detection of nucleoside diphosphatase kinase-A.
AB  - Nucleoside diphosphatase kinase A (NDPK-A) is a metastasis-suppressor protein and
      a biomarker that act on a wide range cancer cells to inhibit the potential
      metastasis. Herein, we present a simple photoelectrochemical immunosensor based
      on ZnO nanorod arrays for the sensitive detection of NDPK-A. The ZnO nanorod
      arrays cosensitized with CdS nanoparticles and Mn2+ displayed a high and stable
      photocurrent response under irradiation. After anti-NPDK-A nanobodies were
      immobilized to the ZnO nanorod arrays, the proposed immunosensor can be utilized
      for detecting NPDK-A by monitoring the changes in the photocurrent signals of the
      electrode resulting from immunoreaction. Accordingly, the well-designed
      immunosensor exhibited a low limit of detection (LOD) of 0.3 pg mL-1 and a wide
      linear range from 0.5 pg mL-1 to 10 MUg mL-1. The R2 of the regression curve is
      0.99782. Meanwhile, the good stability, reproducibility and specificity of the
      resulting photoelectrochemical biosensor are demonstrated. In addition, the
      presented work would offer a novel and simple approach for the detection of
      immunoreactions and provide new insights in popularizing the diagnosis of NPDK-A.

PMID- 28502432
TI  - Carbon dots for fluorescent detection of alpha-glucosidase activity using enzyme
      activated inner filter effect and its application to anti-diabetic drug
      discovery.
AB  - Recently, alpha-glucosidase inhibitor has been widely used in clinic for diabetic
      therapy. In the present study, a facile and sensitive fluorescent assay based on
      enzyme activated inner filter effect (IFE) on nitrogen-doped carbon dots (CDs)
      was first developed for the detection of alpha-glucosidase. The N-doped CDs with
      green emission were prepared by a one-step hydrothermal synthesis and gave the
      fluorescence quantum yield of 30%, which were used as the signal output. Through
      alpha-glucosidase catalysis, 4-nitrophenol was released from 4-nitrophenyl-alpha
      d-glucopyranoside (NGP). Interestingly, the absorption of 4-nitrophenol and the
      excitation of CDs were completely overlapping. Due to its great molar
      absorptivity, 4-nitrophenol was capable of acting as a powerful absorber to
      affect the fluorescent signal of CDs (i.e. IFE). By converting the absorption
      signals into fluorescence signals, the facile fluorescence assay strategy could
      be realized for alpha-glucosidase activity sensing, which effectively avoided the
      complex modification of the surface of CDs or construction of the nanoprobes. The
      established IFE-based sensing platform offered a low detection limit of 0.01 U/mL
      (S/N = 3). This proposed sensing approach has also been expanded to the inhibitor
      screening and showed excellent applicability. As a typical alpha-glucosidase
      inhibitor, acarbose was investigated with a low detection limit of 10-8 M. This
      developed method enjoyed many merits including simplicity, lost cost, high
      sensitivity, good reproducibility and excellent selectivity, which also provided
      a new insight on the application of CDs to develop the facile and sensitive
      biosensor.

PMID- 28502433
TI  - Eosinophilic Gastrointestinal Disorders.
AB  - Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an
      isolated infiltration of eosinophils into the epithelium of the esophagus and is
      triggered by specific allergens. Patients should undergo an upper endoscopy with
      biopsy after 6 to 8 weeks of treatment with a proton pump inhibitor in order to
      make the diagnosis of EoE. Eosinophilic gastroenteritis is a pathologic
      eosinophilic infiltration of any portion of the gastrointestinal tract, and
      eosinophilic proctocolitis is an eosinophilic infiltration in the colon alone.

PMID- 28502434
TI  - Gastroesophageal Reflux Disease.
AB  - Gastroesophageal reflux (GER) is a normal physiologic process. It is important to
      distinguish GER from GER disease (GERD) since GER does not require treatment.
      Although a diagnosis of GERD can largely be based on history and physical alone,
      endoscopy and pH impedance studies can help make the diagnosis when there in
      atypical presentation. In children and adolescents, lifestyle changes and acid
      suppression are first-line treatments for GERD. In infants, acid suppression is
      not effective, but a trial of hydrolyzed formula can be considered, as milk
      protein sensitivity can be difficult to differentiate from GER symptoms.

PMID- 28502435
TI  - Caustic Ingestions and Foreign Bodies Ingestions in Pediatric Patients.
AB  - Children inevitably swallow foreign material accidentally or intentionally. Each
      type of ingestion carries their own set of risks and complications, short and
      long term, some requiring immediate attention while others close monitoring.
      Alkalotic household cleaning products and lithium button batteries are
      increasingly common and damage the esophagus quickly. While many toys with rare
      earth metals are banned, they are already present in many households and can
      cause necrosis of bowel that is between the magnets. This article reviews the
      incidence and assessment along with current literature to provide guidelines for
      management of pediatric patients with suspected caustic or foreign body
      ingestion.

PMID- 28502436
TI  - Abdominal Pain in Children: From the Eternal City to the Examination Room.
AB  - Abdominal pain is a common presenting symptom in children. The differential
      diagnosis of abdominal pain is extensive; however, a vast majority of patients
      ultimately are diagnosed with functional abdominal pain disorders. Functional
      gastrointestinal disorders are defined using the recently released Rome IV
      criteria. These are not diagnoses of exclusion. If there are no alarm signs, the
      diagnosis may be made with a focused evaluation. Treatment of these disorders
      requires a biopsychosocial approach to the disorder and an individualized and
      multipronged treatment plan.

PMID- 28502437
TI  - Gastrointestinal Bleeding and Management.
AB  - There is a broad clinical spectrum of gastrointestinal bleeding in children,
      ranging from subtle laboratory findings to dramatic clinical presentations. This
      review provides a framework for the evaluation and management of gastrointestinal
      hemorrhage for pediatricians. It outlines strategies for obtaining a tailored
      patient history and conducting a thorough physical examination that can shed
      light on the location, severity, and likely etiology of bleeding. It appraises
      blood tests, radiologic tools, and endoscopic modalities frequently used to
      identify and control a source of bleeding.

PMID- 28502439
TI  - Pediatric Inflammatory Bowel Disease.
AB  - Inflammatory bowel disease (IBD), including Crohn disease, ulcerative colitis,
      and IBD-unspecified, is a chronic immune-mediated condition of the
      gastrointestinal tract in which the goal of treatment is to induce and maintain
      durable remission. In pediatrics, there is a wide spectrum of presenting
      symptoms, but esophagogastroduodenoscopy and colonoscopy are imperative to
      confirming the diagnosis. Treatment goals include achieving mucosal healing of
      the gastrointestinal tract, reaching growth potential, limiting medication
      toxicities, and optimizing quality of life for all patients.

PMID- 28502438
TI  - Celiac Disease and Nonceliac Gluten Sensitivity.
AB  - Gluten-related disorders include celiac disease (CD), wheat allergy, and
      nonceliac gluten sensitivity. CD is an autoimmune enteropathy caused by damage to
      small intestinal mucosa when gluten is ingested in genetically susceptible
      individuals. Currently, the only available treatment of CD is gluten-free diet.
      Several potential treatments are being researched. Wheat allergy is a
      hypersensitivity reaction caused by IgE-mediated and/or non-IgE-mediated immune
      response, and can involve the gastrointestinal tract, skin, or respiratory tract.
      Nonceliac gluten sensitivity is one of a variety of immunologic, morphologic, or
      symptomatic manifestations precipitated by ingestion of gluten in individuals in
      whom CD and wheat allergy are excluded.

PMID- 28502440
TI  - Motility Disorders in Children.
AB  - Gastrointestinal motility disorders in the pediatric population are common and
      can range from benign processes to more serious disorders. Performing and
      interpreting motility evaluations in children present unique challenges. There
      are primary motility disorders but abnormal motility may be secondary due to
      other disease processes. Diagnostic studies include radiographic scintigraphic
      and manometry studies. Although recent advances in the genetics, biology, and
      technical aspects are having an important impact and have allowed for a better
      understanding of the pathophysiology and therapy for gastrointestinal motility
      disorders in children, further research is needed to be done to have better
      understanding of the pathophysiology and for better therapies.

PMID- 28502441
TI  - Intestinal Transplant in Children.
AB  - The past decade has seen major advances in the field of transplantation; it is
      the treatment of choice for many with intestinal failure. One-year mortality from
      pediatric intestinal transplantation has significantly declined, from 30% to 10%
      to 15% nationally, mainly due to a multidisciplinary approach in transplant
      centers. Pediatric age carries special considerations along the spectrum of care
      that continue to cause challenges but also offers growth opportunities. Pediatric
      intestinal transplantation indications and timing are changing as a result of new
      developments in diagnostic and treatment tools. This article reviews updates on
      pediatric intestinal transplantation and highlights future directions.

PMID- 28502442
TI  - Neonatal Cholestasis.
AB  - Neonatal jaundice is common and usually not concerning when it is secondary to
      unconjugated hyperbilirubinemia, below the neurotoxic level, and resolves early.
      Primary care providers should be vigilant, however, about evaluating infants in
      whom jaundice presents early, is prolonged beyond 2 weeks of life, or presents at
      high levels. Even in well-appearing infants, fractionated (direct and indirect)
      bilirubin levels should be obtained in these clinical scenarios to evaluate for
      potential cholestasis. This review presents an approach to the evaluation of a
      jaundiced infant and discusses diagnosis and management of several causes of
      neonatal cholestasis.

PMID- 28502445
TI  - Pediatric Liver Transplantation.
AB  - Excellent outcomes over the last 3 decades have made liver transplantation the
      treatment of choice for many advanced liver disorders. This success also opened
      liver transplantation to new indications such as liver tumors and metabolic
      disorders. The emergence of such new indications for liver transplantation is
      bringing a new stream of patients along with disease-specific challenges. The
      cumulative number of liver transplant recipients is peaking, requiring novel
      systems of health care delivery that meet the needs of this special patient
      population. This article reviews updates and new development in pediatric liver
      transplantation.

PMID- 28502444
TI  - Nonalcoholic Fatty Liver Disease in Children: Hepatic and Extrahepatic
      Complications.
AB  - Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation
      of metabolic syndrome and has become the most common form of chronic liver
      disease in children and adolescents. The histologic spectrum of NAFLD is broad
      ranging, from the relatively benign form of simple steatosis to the aggressive
      form of nonalcoholic steatohepatitis, eventually leading to fibrosis and
      cirrhosis. NAFLD has also been recognized as an independent risk factor for
      extrahepatic complications, such as cardiovascular disease, type 2 diabetes
      mellitus, sleep disorders, and osteoporosis. In this review, we discuss both the
      hepatic and extrahepatic complications of NAFLD in children.

PMID- 28502443
TI  - Hepatitis B and C.
AB  - Chronic viral hepatitis is a global health threat and financial burden. Hepatitis
      B and C viruses (HBV and HCV) are the most common causes of chronic viral
      hepatitis in the United States. Most cases are asymptomatic before adulthood.
      Research has resulted in effective therapy for HCV and the promise of effective
      therapies for HBV. For HCV, therapy is pegylated interferon and ribavirin.
      Clinical trials with effective direct-acting antiviral agents are underway in
      pediatrics. For HBV, approved agents are alpha-interferon, lamivudine, adefovir,
      tenofovir, and entecavir. However, treatment seldom results in functional cure
      and more effective therapies are urgently needed.

PMID- 28502447
TI  - The Transition of the Gastrointestinal Patient from Pediatric to Adult Care.
AB  - Transition is the long process of developing independent self-management skills
      whereas transfer is the actual move from pediatric to adult-centered provider.
      Structured anticipated transition works best with timelines of tasks to master
      and discussion of the stylistic differences between pediatric and adult
      practices. Disease-specific issues need to be addressed, such as earlier
      timelines for diet-based therapies, parental support for critical illnesses, and
      differences in therapeutic strategies.

PMID- 28502448
TI  - The Remarkable Gastrointestinal Tract.

PMID- 28502446
TI  - Pancreatic Disorders.
AB  - Once considered uncommon, pancreatic diseases are increasingly recognized in the
      pediatric age group. Acute pancreatitis, acute recurrent pancreatitis, and
      chronic pancreatitis occur in children with an incidence approaching that of
      adults. Risk factors are broad, prompting the need for a completely different
      diagnostic and therapeutic approach in children. Although cystic fibrosis remains
      the most common cause of exocrine pancreatic insufficiency, other causes such as
      chronic pancreatitis may be as common as Shwachman Diamond syndrome. Long-term
      effects of pancreatic diseases may be staggering, as children suffer from
      significant disease burden, high economic cost, nutritional deficiencies,
      pancreatogenic diabetes, and potentially pancreatic cancer.

PMID- 28502449
TI  - Pediatric Gastroenterology.

PMID- 28502450
TI  - In This Issue....

PMID- 28502452
TI  - The impact of submarine copper mine tailing disposal from the 1970s on
      Repparfjorden, northern Norway.
AB  - We investigate the state of sedimentological environment and contaminant status
      of Repparfjorden (N Norway) impacted by submarine disposal of mine tailings
      during the 1970s using sedimentological and geochemical properties of seventeen
      sediment cores. The impact of tailings disposal is mainly restricted to the inner
      fjord where the discharge occurred. Sediment cores retrieved from the inner fjord
      contain layers of mine tailings up to 9-cm thick, 3-9cm below the seafloor.
      Spreading of the tailing-related metal Cu and particles is limited to the inner
      fjord and to a 2cm layer in one core from the outer fjord. Two interrelated
      factors, fjord morphology and sedimentation rate, controlled the distribution of
      contaminant-laden tailings in the fjord. The mobility of Cu from buried
      contaminated sediments to the sediment-water interface in the inner fjord
      indicates that benthic communities have been continuously exposed to elevated Cu
      concentrations for nearly four decades.

PMID- 28502451
TI  - Benefits and shortcomings of non-destructive benthic imagery for monitoring hard
      bottom habitats.
AB  - Hard-bottom habitats with complex topography and fragile epibenthic communities
      are still not adequately considered in benthic monitoring programs, despite their
      potential ecological importance. While indicators of ecosystem health are defined
      by major EU directives, methods commonly used to measure them are deficient in
      quantification of biota on hard surfaces. We address the suitability of seafloor
      imaging for monitoring activities. We compared the ability of high-resolution
      imagery and physical sampling methods (grab, dredge, SCUBA-diving) to detect
      taxonomic and functional components of epibenthos. Results reveal that (1) with
      minimal habitat disturbance on large spatial scales, imagery provides valuable,
      cost-effective assessment of rocky reef habitat features and community structure,
      (2) despite poor taxonomic resolution, image-derived data for habitat-forming
      taxa might be sufficient to infer richness of small sessile and mobile fauna, (3)
      physical collections are necessary to develop a robust record of species
      richness, including species-level taxonomic identifications, and to establish a
      baseline.

PMID- 28502453
TI  - Petroleum hydrocarbon toxicity to corals: A review.
AB  - The proximity of coral reefs to coastal urban areas and shipping lanes
      predisposes corals to petroleum pollution from multiple sources. Previous
      research has evaluated petroleum toxicity to coral using a variety of
      methodology, including monitoring effects of acute and chronic spills, in situ
      exposures, and ex situ exposures with both adult and larval stage corals.
      Variability in toxicant, bioassay conditions, species and other methodological
      disparities between studies prevents comprehensive conclusions regarding the
      toxicity of hydrocarbons to corals. Following standardized protocols and
      quantifying the concentration and composition of toxicant will aid in comparison
      of results between studies and extrapolation to actual spills.

PMID- 28502454
TI  - Seasonal and spatial variations of marine litter on the south-eastern Black Sea
      coast.
AB  - The south-eastern Black Sea coast in Turkey was evaluated for marine litter
      composition and density covering nine beaches during four seasons. The marine
      litter (>2cm in size), was collected from the coast and categorized into material
      and usage categories. The data analysis showed that plastic was the most abundant
      litter (>=61.65%) by count and weight followed by styrofoam and fabric. The
      marine litter density ranged from 0.03 to 0.58 with a mean (+/-SD) of 0.16+/-0.02
      items/m2 by count. Based on weight, it varied between 0.44 and 14.74g/m2 with
      3.35+/-1.63. The east side had a higher marine litter density than the west side
      with significant differences between beaches. The variations due to different
      seasons were not significant for any beach. The results of this study should
      provide baseline information about the coastal marine pollution and will assist
      the mitigation strategies.

PMID- 28502455
TI  - Seasonal changes in stress biomarkers of an exotic coastal species - Chaetopleura
      angulata (Polyplacophora) - Implications for biomonitoring.
AB  - Knowledge on baseline values of stress biomarkers in natural conditions is urgent
      due to the need of reference values for monitoring purposes. Here we assessed the
      cellular stress response of the chiton Chaetopleura angulata in situ. Biomarkers
      commonly used in environmental monitoring (heat shock protein 70kDa, total
      ubiquitin, catalase, glutathione-S-transferase, superoxide-dismutase, lipid
      peroxidation) were analyzed in the digestive system, gills and muscle of C.
      angulata, under spring and summer conditions in order to assess seasonal tissue
      specific responses. Season had an effect on all targeted organs, especially
      affecting the digestive system which displayed clear seasonal clusters. The
      respective Integrated Biomarker Response (IBR) showed a 7.2-fold seasonal
      difference. Muscle and gills showed similar IBRs between seasons making them
      appropriate organs to monitor chemical pollution as they were less responsive to
      seasonal variation. The most stable biomarkers in these organs were ubiquitin and
      superoxide-dismutase thus being reliable for monitoring purposes.

PMID- 28502456
TI  - Successful Team-Based Management of Renal Cell Carcinoma With Caval Extension of
      Tumor Thrombus Above the Diaphragm.

PMID- 28502457
TI  - Anesthesia for Pulmonary Endarterectomy and Extracorporeal Membrane Oxygenation
      in a Patient With Achondroplasia.

PMID- 28502458
TI  - Acute Pulmonary Hemorrhage Following Radiofrequency Ablation of Atrial
      Fibrillation.

PMID- 28502459
TI  - Discovery of indolin-2-one derivatives as potent PAK4 inhibitors: Structure
      activity relationship analysis, biological evaluation and molecular docking
      study.
AB  - Utilizing a pharmacophore hybridization approach, a novel series of substituted
      indolin-2-one derivatives were designed, synthesized and evaluated for their in
      vitro biological activities against p21-activated kinase 4. Compounds 11b, 12d
      and 12g exhibited the most potent inhibitory activity against PAK4 (IC50=22nM,
      16nM and 27nM, respectively). Among them, compound 12g showed the highest
      antiproliferative activity against A549 cells (IC50=0.83MUM). Apoptosis analysis
      in A549 cells suggested that compound 12g delayed cell cycle progression by
      arresting cells in the G2/M phase of the cell cycle, retarding cell growth.
      Further investigation demonstrated that compound 12g strongly inhibited migration
      and invasion of A549 cells. Western blot analysis indicated that compound 12g
      potently inhibited the PAK4/LIMK1/cofilin signalling pathways. Finally, the
      binding mode between compound 12g with PAK4 was proposed by molecular docking. A
      preliminary ADME profile of the compound 12g was also drawn on the basis of
      QikProp predictions.

PMID- 28502461
TI  - Meta-Analysis of Effects of Voluntary Slow Breathing Exercises for Control of
      Heart Rate and Blood Pressure in Patients With Cardiovascular Diseases.
AB  - Rising heart rate (HR) and elevated blood pressure (BP) cause a greater frequency
      of cardiovascular events. Many patients cannot maintain target HR and BP using
      pharmacological therapies. To evaluate the effectiveness of voluntary slow
      breathing exercises in reducing resting HR and BP, we searched Embase (1974 to
      April 2016), PubMed (1966 to April 2016), the Cochrane Central Register of
      Controlled Trials (issue 4, April 2016), and PEDro (www.pedro.org.au; 1999 to
      April 2016). The primary outcome was the mean change in HR at rest. Secondary
      outcomes included changes in systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) as well as compliance with the breathing training. Finally, we
      included 6 studies consisting of 269 subjects. Practice of the breathing
      exercises resulted in statistically significant HR reduction (mean difference: 
      1.72 beats/min, 95% CI -2.70 to -0.75). Reductions were seen in SBP (mean
      difference: -6.36 mm Hg, 95% CI -10.32 to -2.39) and DBP (mean difference: -6.39
      mm Hg, 95% CI -7.30 to -5.49) compared with the controls. Trial durations ranged
      from 2 weeks to 6 months. In conclusion, the existing evidence from randomized
      controlled trails demonstrates that short-term voluntary slow breathing exercises
      can reduce resting HR, SBP, and DBP for patients with cardiovascular diseases.

PMID- 28502460
TI  - Can the Use of Bone Marrow Parameters Improve the Efficacy of Risk Prediction
      Scores in Chronic Myeloid Leukemia in Imatinib Era?
AB  - INTRODUCTION: Many attempts have been made to develop risk prediction scores for
      chronic myeloid leukemia in chronic phase (CML-CP) to identify the subgroup with
      a poorer response to therapy to enable early intensification of treatment.
      Because the bone marrow (BM) provides a more sensitive reflection of the disease
      process, we hypothesized that using BM parameters in the Sokal and European
      Treatment and Outcome Study (EUTOS) risk scores could improve their efficacy in
      an imatinib-treated population. MATERIALS AND METHODS: We analyzed cases of CML
      CP for their response and survival outcomes with imatinib using risk groupings
      determined by the Sokal and EUTOS scores using peripheral blood (PB) or BM
      parameters (Sokal-PB, Sokal-BM, EUTOS-PB, and EUTOS-BM). RESULTS: A total of 371
      cases were analyzed. The concordance for risk groups was greater for the EUTOS
      scores (81.9%) than for the Sokal scores (68.1%) using PB versus BM parameters.
      For all 4 risk scores, the predictive efficacy was statistically significant.
      EUTOS-PB and EUTOS-BM could better prognosticate for progression-free survival
      (PFS) and overall survival (OS) between the low- and high-risk groups (P <
      .0001). However, with the Sokal risk score, the use of BM parameters improved the
      prognostic capacity for PFS between the low- and intermediate-risk groups, with a
      statistically significant difference (P = .025), but not for OS (P = .88).
      CONCLUSION: The use of BM parameters, a simple method that is feasible in routine
      clinical practice could improve the prognostic efficacy of the Sokal score for
      PFS but not for OS in low- and intermediate-risk groups. Further research to
      improve the sensitivity of risk scores for CML-CP prognosis and attempts at risk
      directed therapy is warranted.

PMID- 28502463
TI  - Greening the Radiology Department: Not a Big Mountain to Climb.
AB  - An environmental-friendly radiology department should be a requirement of the
      future era. The aim of this article is to make radiologists aware of their
      responsibilities for a greener world. We have suggested a number of minor but
      important changes in various sections of a radiology department that can make the
      radiology department more environmentally friendly. These small steps require
      relatively little effort on our part but cumulatively, may have a huge positive
      impact on our environment.

PMID- 28502462
TI  - Radiology Exposure in the Undergraduate Curriculum: A Medical Student Perspective
      on Quality and Opportunities for Positive Change.
AB  - PURPOSE: This article is a continuation of a qualitative study designed to
      explore how radiology exposures can impact medical student opinions and
      perceptions of radiology and radiologists. We focused on: 1) conducting a
      radiology exposure inventory from the perspective of the medical student; 2)
      student evaluation of the quality of the radiology exposures and suggestions for
      positive change; and 3) development of a framework to address the needs of
      medical students as it relates to radiology education in the undergraduate
      medical curriculum. METHODS: Research methodology and design for this qualitative
      study were described in detail in a previous article by Visscher et al [1].
      RESULTS: Participants included 28 medical students; 18 were in medical school
      years 1 and 2 (preclerkship), and 10 were in years 3 and 4 (clerkship). Specific
      to the focus of this article, the data revealed 3 major findings: 1) multiple
      exposures to radiology exist, and they are received and valued differently
      depending on the medical student's stage of professional development; 2) medical
      students value radiology education and want their radiology exposure to be
      comprehensive and high quality; 3) Medical students have constructive suggestions
      for improving the quality of both formal and informal radiology exposures.
      CONCLUSIONS: Performing a radiology exposure inventory from a medical student
      perspective is a useful way to explore how students receive and value radiology
      instruction. Medical students want a more comprehensive radiology education that
      can be summarized using the 5 C's of Radiology Education framework. The 5 C's
      (curriculum, coaching, collaborating, career and commitment) reflect medical
      students' desires to learn content that will support them in clinical practice,
      be supported in their professional development, and have the necessary
      information to make informed career decisions.

PMID- 28502464
TI  - Small signs, important diagnoses.

PMID- 28502465
TI  - Application of NMR to studies of intrinsically disordered proteins.
AB  - The prevalence of intrinsically disordered protein regions, particularly in
      eukaryotic proteins, and their clear functional advantages for signaling and gene
      regulation have created an imperative for high-resolution structural and
      mechanistic studies. NMR spectroscopy has played a central role in enhancing not
      only our understanding of the intrinsically disordered native state, but also how
      that state contributes to biological function. While pathological functions
      associated with protein aggregation are well established, it has recently become
      clear that disordered regions also mediate functionally advantageous assembly
      into high-order structures that promote the formation of membrane-less sub
      cellular compartments and even hydrogels. Across the range of functional assembly
      states accessed by disordered regions, post-translational modifications and
      regulatory macromolecular interactions, which can also be investigated by NMR
      spectroscopy, feature prominently. Here we will explore the many ways in which
      NMR has advanced our understanding of the physical-chemical phase space occupied
      by disordered protein regions and provide prospectus for the future role of NMR
      in this emerging and exciting field.

PMID- 28502466
TI  - Purification and site-directed mutagenesis of linoleate 9S-dioxygenase-allene
      oxide synthase of Fusarium oxysporum confirms the oxygenation mechanism.
AB  - Plants and fungi form jasmonic acid from alpha-linolenic acid. The first two
      steps of biosynthesis in plants occur by sequential transformation by 13S
      lipoxygenase and allene oxide synthase (AOS). The biosynthesis in fungi may
      follow this classical scheme, but the only fungal AOS discovered so far are
      cytochromes P450 (CYP) fused to 8- and 9-dioxygenases (DOX). In the present
      report, we purified recombinant 9S-DOX-AOS of Fusarium oxysporum from cell lysate
      by cobalt affinity chromatography to near homogeneity and studied key residues by
      site-directed mutagenesis. Sequence homology with 8R-DOX-linoleate diol synthases
      (8R-DOX-LDS) suggested that Tyr414 catalyzes hydrogen abstraction and that
      Cys1051 forms the heme thiolate ligand. Site-directed mutagenesis (Tyr414Phe;
      Cys1051Ser) led to loss of 9S-DOX and 9S-AOS activities, respectively, but other
      important residues in the CYP parts of 5,8- and 7,8-LDS or 9R-AOS were not
      conserved. The UV-visible spectrum of 9S-DOX-AOS showed a Soret band at 409 nm,
      which shifted to 413 nm in the Cys1051Ser mutant. The 9S-AOS of the Tyr414Phe
      mutant transformed 9S-hydroperoxides of alpha-linolenic and linoleic acids to
      allene oxides/alpha-ketols, but it did not transform 13-hydroperoxides. We
      conclude that 9S- and 8R-DOX catalyze hydrogen abstraction at C-11 and C-8,
      respectively, by homologous Tyr residues.

PMID- 28502467
TI  - Remarks to the debate on mapping heavy metals in soil and soil monitoring in the
      European Union.
AB  - We provide an overview of the main features of the LUCAS topsoil survey of the EU
      in comparison to the GEMAS survey. In addition we describe the policy
      requirements and scientific principles of soil monitoring programs.

PMID- 28502468
TI  - Magnetically assisted matrix solid phase dispersion for extraction of parabens
      from breast milks.
AB  - In the present work, magnetically assisted matrix solid phase dispersion (MA
      MSPD) was used as an efficient solid phase extraction method. MA-MSPD followed by
      a dispersive liquid-liquid microextraction (DLLME) was applied for determination
      of parabens in breast milks. The analysis were performed using LC-UV and LC
      MS/MS. Poly(indole-thiophene) coated magnetic graphene oxide (MGO@PIT) was
      synthesized, characterized and used as the sorbent. Na2SO4 was used as the drying
      salt as well as matrix dispersing agent. Exact amounts of MGO@PIT and Na2SO4 were
      added into 200MUL volume of the milk and the mixture was gently blended to obtain
      a dry powder. The blend was dispersed into ultrapure water and stirred. Because
      of dissolving of the matrix dispersant in water, only the magnetic sorbent is
      remained into water which can be easily separated by a magnet. Next, the sorbent
      was eluted with a suitable solvent to desorb the analyte and the eluent was used
      as the disperser solvent for the subsequent DLLME. In this approach, the target
      analytes were directly adsorbed on the surface of the magnetic sorbent without
      any sample pretreatment. Compared with conventional MSPD, MA-MSPD increases the
      simplicity of the extraction procedure, decreases the extraction time and
      eliminates the column packing as well as its related drawbacks. The optimum
      extraction parameters were obtained as 50mg of MGO@PIT, 550mg of Na2SO4 in 200MUL
      of the milk sample, 1.0mL of methanol as the eluent solvent under fierce vortex
      for 2.0min and 100MUL of 1-octanol as the extraction solvent. Under the optimal
      conditions, the extraction recoveries greater than 83% were obtained, and LOD and
      LOQ values were found 25ngmL-1 (about 0.5ngmL-1 by LC-MS/MS) and 50ngmL-1 using
      LC-UV, respectively. The calibration curves were in the range of 50-4000ngmL-1
      with the determination coefficients (R2) higher than 0.998. Relative standard
      deviations (RSD%) for intra- and inter-day precisions were less than 7.5% and
      11.3%, respectively. The results confirmed that the proposed method is a rapid,
      feasible and convenient technique which makes it suitable for the analysis of
      parabens from breast milk samples.

PMID- 28502471
TI  - Reference Standards for Gene and Cell Therapy Products.

PMID- 28502469
TI  - Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair
      in Corneal Injury.
AB  - Corneal injuries are among the major causes of ocular morbidity and vision
      impairment. Optimal epithelial wound healing is critical for the integrity and
      transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a
      mitogen and motility factor that primarily regulates epithelial cell function.
      Herein, we investigate the effect of HGF on proliferation of corneal epithelial
      cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate
      that HGF not only promotes CEC proliferation in homeostatic conditions but also
      reverses the anti-proliferative effect of the inflammatory environment on these
      cells. Furthermore, using a mouse model of ocular injury, we show that HGF
      treatment suppresses ocular inflammation and actively augments CEC proliferation,
      leading to improved and accelerated corneal epithelial repair. These findings
      have potential translational implications and could provide a framework for the
      development of novel HGF-based therapies for corneal epithelial defects.

PMID- 28502470
TI  - Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to
      Glioma.
AB  - The effective treatment of glioma is largely hindered by the poor transfer of
      drug delivery systems across the blood-brain barrier (BBB) and the difficulty in
      distinguishing healthy and tumorous cells. In this work, for the first time, an
      interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting
      ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine
      oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide
      provides multiple functions, including the cascade-targeting potential
      represented by a combined BBB-crossing and subsequent glioma-targeting ability,
      as well as a direct tumor-inhibiting effect. I6P7-Stp-His/DNA nanoparticles (NPs)
      mediated higher gene expression in human glioma U87 cells than in healthy human
      astrocytes and a deeper penetration into glioma spheroids than scrambled peptide
      modified NPs. Transport of I6P7-modified, but not the control, NPs across the BBB
      was demonstrated in vitro in a transwell bEnd.3 cell model resulting in
      transfection of underlying U87 cells and also in vivo in glioma-bearing mice.
      Intravenous administration of I6P7-Stp-His/plasmid DNA (pDNA)-encoding inhibitor
      of growth 4 (pING4) significantly prolonged the survival time of orthotopic U87
      glioma-bearing mice. The results denote that I6P7 peptide is a roborant cascade
      targeting ligand, and I6P7-modified NPs might be exploited for efficient glioma
      therapy.

PMID- 28502472
TI  - A novel concept for tumour targeting with radiation: Inverse dose-painting or
      targeting the "Low Drug Uptake Volume".
AB  - BACKGROUND AND PURPOSE: We tested a novel treatment approach combining (1)
      targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug
      TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic
      tumour sub-volumes having no/low drug uptake. MATERIAL AND METHODS: 18F-HX4
      hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a
      surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent
      rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV
      with the lowest or highest 18F-HX4 uptake, respectively. Two hours post TH
      302/saline administration, animals received either single dose radiotherapy (RT)
      uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50%
      higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse
      treatment planning system and radiation was delivered using VMAT. Tumour response
      was quantified as time to reach 3 times starting tumour volume. RESULTS: Non
      uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior
      to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean
      dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average
      3.5Gy lower dose to the GTV to achieve similar tumour response as uniform dose
      escalation. CONCLUSIONS: The results support targeted dose escalation to non
      hypoxic tumour sub-volume with no/low activity of hypoxia-activated prodrugs.
      This strategy applies on average a lower radiation dose and is as effective as
      uniform dose escalation to the entire tumour. It could be applied to other type
      of drugs provided that their distribution can be imaged.

PMID- 28502473
TI  - Salvage radiation therapy after prostatectomy: Understanding the dose-response
      effect.

PMID- 28502474
TI  - [Role of prostate MRI, TRUS fusion biopsies and new markers in the diagnostic
      strategy of prostate cancer].
AB  - Multiparametric MRI prostate (mp-MRI) is a powerful tool to locate lesions>0.5cm3
      (below this threshold tumor volume, prostate cancers are classified as
      "insignificant"). The detection rate of the mp-MRI for significant cancers of
      small volume (0.5-1cm3) with a Gleason score>=7 is>85 %. The prostate mp-MRI
      optimizes the management of cancers classified as low risk of progression by
      providing aggressive criteria for misclassified lesions, which require an active
      treatment and enhance the clinicopathological criteria of indolence for
      subclinical lesions, which can justify of surveillance. MRI-mp coupled to the 3D
      ultrasound image fusion, optimizes the predictive value of biopsies and improves
      tumor staging, particularly when benign prostatic hyperplasia (>40cm3) is
      associated with clinical course. New tissue markers feasible on biopsies allow to
      define better the risk of progression of the small volume of cancer in order to
      reinforce the indications of surveillance or delayed curative treatment.

PMID- 28502476
TI  - Purkinje Cells Are More Vulnerable to the Specific Depletion of Cathepsin D Than
      to That of Atg7.
AB  - Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of
      neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the
      maintenance of metabolism in central nervous system neurons. To further
      understand the role of CTSD in central nervous system neurons, we generated mice
      with a CTSD deficiency specifically in the Purkinje cells (PCs)
      (CTSDFlox/Flox;GRID2-Cre) and compared their phenotypes with those of PC
      selective Atg7-deficient (Atg7Flox/Flox;GRID2-Cre) mice. In both strains of mice,
      PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly
      than their Atg7-deficient counterparts. When CTSD-deficient PCs died, the
      neuronal cell bodies became shrunken, filled with autophagosomes and
      autolysosomes, and had nuclei with dispersed small chromatin fragments. The dying
      Atg7-deficient PCs also showed similar ultrastructures, indicating that the
      neuronal cell death of CTSD- and Atg7-deficient PCs was distinct from apoptosis.
      Immunohistochemical observations showed the formation of calbindin-positive
      axonal spheroids and the swelling of vesicular GABA transporter-positive
      presynaptic terminals that were more pronounced in Atg7-deficient PCs than in
      CTSD-deficient PCs. An accumulation of tubular vesicles may have derived from the
      smooth endoplasmic reticulum; nascent autophagosome-like structures with double
      membranes was a common feature in the swollen axons of these PCs. These results
      suggested that PCs were more vulnerable to CTSD deficiency in lysosomes than to
      autophagy impairment, and this vulnerability does not depend on the severity of
      axonal swelling.

PMID- 28502475
TI  - Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2
      (rhBMP-2) Augmented Sheep Spinal Fusion.
AB  - Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP
      2) have reported complications. However, the local adverse effects of rhBMP-2
      application are not well documented. In this report we show that, in addition to
      promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2
      augmentation promotes local cyst-like osteolytic formations in sheep trabecular
      bones that have undergone anterior lumbar interbody fusion. Three months after
      operation, conventional computed tomography showed that the trabecular bones of
      the rhBMP-2 application groups could fuse, whereas no fusion was observed in the
      control group. Micro-computed tomography analysis revealed that the core implant
      area's bone volume fraction and bone mineral density increased proportionately
      with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant
      areas when using rhBMP-2 applications, and these sites showed significant bone
      mineral density decreases in relation to the unaffected regions. Biomechanically,
      these areas decreased in strength by 32% in comparison with noncystic areas.
      Histologically, rhBMP-2-affected void sites had an increased amount of fatty
      marrow, thinner trabecular bones, and significantly more adiponectin- and
      cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in
      clinical applications may result in local adverse structural alterations and
      compromised biomechanical changes to the bone.

PMID- 28502478
TI  - The Cellular Retinoic Acid Binding Protein 2 Promotes Survival of Malignant
      Peripheral Nerve Sheath Tumor Cells.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive neoplasms that
      commonly occur in patients with neurofibromatosis type 1 (NF1). Effective
      chemotherapy is not available. To characterize a therapeutic target for
      treatment, we investigated the role of cellular retinoic acid binding protein 2
      (CRABP2) in MPNST in vitro. CRABP2 is a transcriptional co-activator of retinoic
      acid signaling. Although overexpression of CRABP2 is described in several
      cancers, it has not yet been studied in MPNSTs. We investigated CRABP2 expression
      in cultured Schwann cells and formalin-fixed, paraffin-embedded specimens of
      human peripheral nerve sheath tumors. A transient knockdown of CRABP2 was
      established in human NF1-associated MPNST cell lines (S462, T265, NSF1), and
      functional effects on viability, proliferation, apoptosis, and cytotoxicity were
      monitored. Finally, a 45-pathway reporter assay was performed in knockdown cells.
      Expression of CRABP2 was found in epithelium, fibroblasts, and tumor Schwann
      cells of skin, neurofibromas, and MPNSTs. In contrast, normal skin Schwann cells
      (NF1+/-, NF1-/-) did not express CRABP2. In the absence of retinoic acid, MPNST
      cells depleted of CRABP2 had reduced viability and proliferation, induction of
      apoptosis and cytotoxicity, and up-regulation of the type 1 interferon pathway.
      These data suggest a retinoic acid-independent, non-tumor suppressor role of
      CRABP2 for the survival of MPNST cells in vitro. Targeting CRABP2 overexpression
      may represent a unique approach for the treatment of human MPNSTs.

PMID- 28502477
TI  - Knockdown of Hepatic Gonadotropin-Releasing Hormone by Vivo-Morpholino Decreases
      Liver Fibrosis in Multidrug Resistance Gene 2 Knockout Mice by Down-Regulation of
      miR-200b.
AB  - Hepatic fibrosis occurs during the progression of primary sclerosing cholangitis
      (PSC) and is characterized by accumulation of extracellular matrix proteins.
      Proliferating cholangiocytes and activated hepatic stellate cells (HSCs)
      participate in the promotion of liver fibrosis during cholestasis. Gonadotropin
      releasing hormone (GnRH) is a trophic peptide hormone synthesized by hypothalamic
      neurons and the biliary epithelium and exerts its biological effects on
      cholangiocytes by interaction with the receptor subtype (GnRHR1) expressed by
      cholangiocytes and HSCs. Previously, we demonstrated that administration of GnRH
      to normal rats increased intrahepatic biliary mass (IBDM) and hepatic fibrosis.
      Also, miR-200b is associated with the progression of hepatic fibrosis; however,
      the role of the GnRH/GnRHR1/miR-200b axis in the development of hepatic fibrosis
      in PSC is unknown. Herein, using the mouse model of PSC (multidrug resistance
      gene 2 knockout), the hepatic knockdown of GnRH decreased IBDM and liver
      fibrosis. In vivo and in vitro administration of GnRH increased the expression of
      miR-200b and fibrosis markers. The GnRH/GnRHR1 axis and miR-200b were up
      regulated in human PSC samples. Cetrorelix, a GnRHR1 antagonist, inhibited the
      expression of fibrotic genes in vitro and decreased IBDM and hepatic fibrosis in
      vivo. Inhibition of miR-200b decreased the expression of fibrosis genes in vitro
      in cholangiocyte and HSC lines. Targeting the GnRH/GnRHR1/miR-200b axis may be
      key for the management of hepatic fibrosis during the progression of PSC.

PMID- 28502480
TI  - Stenotrophomonas maltophilia in a university hospital of traditional Chinese
      medicine: molecular epidemiology and antimicrobial resistance.
AB  - Stenotrophomona maltophilia has emerged as an important opportunistic pathogen
      that is highly antibiotic resistant. Analysis of antibiotic susceptibilities,
      drug-resistant gene profiles and molecular typing of S. maltophilia was
      undertaken in a university hospital of traditional Chinese medicine in East
      China. Resistance to sulphamethoxazole (SXT) was found to be an indicator of
      multi-drug resistance. SXT resistance was mediated by sul and dfrA genes in
      integrons, especially class 1. Some evidence of clonal dissemination was found,
      indicating the occurrence of cross-transmission of antibiotic-resistant strains
      within the hospital. This underscores the need for effective control and
      prevention measures in hospitals.

PMID- 28502481
TI  - Incidence of colonization of central venous catheter and arterial catheter tips
      in a paediatric intensive care unit.

PMID- 28502479
TI  - Megakaryocytes in Myeloproliferative Neoplasms Have Unique Somatic Mutations.
AB  - Myeloproliferative neoplasms (MPNs) are a group of related clonal hemopoietic
      stem cell disorders associated with hyperproliferation of myeloid cells. They are
      driven by mutations in the hemopoietic stem cell, most notably JAK2V617F, CALR,
      and MPL. Clinically, they have the propensity to progress to myelofibrosis and
      transform to acute myeloid leukemia. Megakaryocytic hyperplasia with abnormal
      features are characteristic, and it is thought that these cells stimulate and
      drive fibrotic progression. The biological defects underpinning this remain to be
      explained. In this study we examined the megakaryocyte genome in 12 patients with
      MPNs to determine whether there are somatic variants and whether there is any
      association with marrow fibrosis. We performed targeted next-generation
      sequencing for 120 genes associated with myeloid neoplasms on megakaryocytes
      isolated from aspirated bone marrow. Ten of the 12 patients had genomic defects
      in megakaryocytes that were not present in nonmegakaryocytic hemopoietic marrow
      cells from the same patient. The greatest allelic burden was in patients with
      increased reticulin deposition. The megakaryocyte-unique mutations were
      predominantly in genes that regulate chromatin remodeling, chromosome alignment,
      and stability. These findings show that genomic abnormalities are present in
      megakaryocytes in MPNs and that these appear to be associated with progression to
      bone marrow fibrosis.

PMID- 28502482
TI  - Compliance with clothing regulations and traffic flow in the operating room: a
      multi-centre study of staff discipline during surgical procedures.
AB  - This multi-centre study assessed operating room (OR) staff compliance with
      clothing regulations and traffic flow during surgical procedures. Of 1615
      surgical attires audited, 56% respected the eight clothing measures. Lack of
      compliance was mainly due to inappropriate wearing of jewellery (26%) and head
      coverage (25%). In 212 procedures observed, a median of five people
      [interquartile range (IQR) 4-6] were present at the time of incision. The median
      frequency of entries to/exits from the OR was 10.6/h (IQR 6-29) (range 0-93).
      Reasons for entries to/exits from the OR were mainly to obtain materials required
      in the OR (N=364, 44.5%). ORs with low compliance with clothing regulations
      tended to have higher traffic flows, although the difference was not significant
      (P=0.12).

PMID- 28502483
TI  - A case report of wound site seeding following cholecystectomy for dysplastic
      gallbladder.
AB  - Wound site metastasis following cholecystectomy is an uncommon but well
      recognised complication following laparoscopic surgery for unsuspected
      gallbladder carcinoma. We describe a case of implantation of dysplastic cells
      with subsequent malignant transformation at the incision site 3 years post
      cholecystectomy for an inflamed gallbladder. Histopathological examination of
      this tumour confirmed adenocarcinoma of pancreatobiliary origin, possibly
      secondary to gallbladder cells implantation and subsequent carcinomatous change.
      Unlike previously reported cases, the present case has two unique features:
      Firstly, the histology of the resected gallbladder at the initial operation was
      that of a low-grade dysplasia and not carcinoma; and secondly, there was a long
      interval between initial surgery and subsequent development of the wound site
      tumour. This case highlights that careful handling of the specimen tissue
      intraoperatively is paramount as cells implanted in the wound site can survive
      and undergo malignant transformation. All new masses occurring along the surgical
      wound site should be followed up and investigated to exclude implanted tumours.

PMID- 28502485
TI  - Low crowding agent concentration destabilizes against pressure unfolding.
AB  - The concentration of macromolecules inside a cell is very high, which can affect
      the behavior of the enzymes, and consequently influence vital biological
      processes. This is called macromolecular crowding. Since the most important
      effect of macromolecular crowding is the excluded volume, we performed pressure
      experiments, where the volume (as conjugate parameter to the pressure) is the
      crucial factor. We measured the temperature and pressure stability of bovine
      serum albumin and lysozyme with various concentrations of crowding agents,
      dextran, FicollTM and lysozyme itself. Our most interesting finding is that low
      concentration of all the studied crowding agents decreases the pressure stability
      of the proteins. We explain this by the reduced hydration volume change in the
      crowded environment. Furthermore, we discuss the volumetric parameters and
      emphasize the difference between the partial volume of the protein and the volume
      it influences, and their relation to the excluded volume which is responsible for
      the macromolecular crowding.

PMID- 28502484
TI  - Pathogenic Abeta A2V versus protective Abeta A2T mutation: Early stage
      aggregation and membrane interaction.
AB  - We investigated the effects of punctual A-to-V and A-to-T mutations in the
      amyloid precursor protein APP, corresponding to position 2 of Abeta1-42. Those
      mutations had opposite effects on the onset and progression of Alzheimer disease,
      the former inducing early AD pathology and the latter protecting against the
      onset of the disease. We applied Static and Dynamic Light Scattering and Circular
      Dichroism, to study the different mutants in the early stages of the aggregation
      process, essential for the disease. Comparative results showed that the
      aggregation pathways differ in the kinetics and extent of the process, in the
      size of the aggregates and in the evolution of the secondary structure, resulting
      in fibrils of different morphology, as seen by AFM. Mutated peptides had
      comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering,
      all of them displayed disordering effects on the internal structure of mixed
      phospholipids-gangliosides model membranes.

PMID- 28502487
TI  - "Mutation-negative" familial hypercholesterolemia-When negative is positive.

PMID- 28502486
TI  - JCL roundtable: Cardiovascular disease risk reduction in menopausal women.
AB  - Ovarian failure occurs in most women during the late fifth decade or early sixth
      decade of life. This causes a number of changes in physiology as estrogen and
      progestin concentrations decline. These involve lipoprotein metabolism and the
      vasculature. The risk factors for large vessel disease increase, and dysfunction
      of the small resistance vessels responds with changes in blood flow to the skin
      causing unpleasant symptoms. These and other changes result in visits to the
      physician. A reassessment of risk factors and symptoms is needed to develop a new
      plan for effective management, both short term and long term.

PMID- 28502488
TI  - Lipoprotein-associated phospholipase A2 and its relationship with markers of
      subclinical cardiovascular disease: A systematic review.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that
      exhibits proinflammatory properties and has been associated with subclinical
      cardiovascular disease. OBJECTIVE: The relationship between Lp-PLA2 and
      subclinical CVD remains unclear. The goal of this systematic review was to
      clarify this relationship. METHODS: An extensive literature search of the MEDLINE
      database using Ovid and PubMed was performed. From an initial search of 444
      articles, 13 met the inclusion and exclusion criteria and were included in the
      review. RESULTS: Of the 13 studies included in the review, 6 examined the
      relationship between Lp-PLA2 and coronary artery calcification, of which 3 showed
      a significant correlation. Two studies examined the relationship between Lp-PLA2
      and endothelial dysfunction, and 1 reported a significant relationship. Five
      studies investigated the association of Lp-PLA2 with carotid intima-media
      thickness (CIMT), and 3 reported a significant relationship. CONCLUSIONS: This
      review shows a variable association between Lp-PLA2 and subclinical disease. This
      finding has broad implications for the future of public health and clinical
      practice. Future research is needed to clarify what role Lp-PLA2 has in guiding
      treatment and if it is involved in plaque instability, which would make it a
      useful tool for risk prognostication.

PMID- 28502489
TI  - Dietary carbohydrate and fat intakes are differentially associated with lipid
      abnormalities in Korean adults.
AB  - BACKGROUND: A high prevalence of metabolic syndrome along with increasing rates
      of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides
      (TGs) is shown in Korean adults. Little is known about the associations between
      macronutrient intake and lipid abnormalities in the Asian population, whose major
      energy source is carbohydrates. OBJECTIVE: We examined the associations of
      dietary carbohydrate and fat intakes with lipid abnormalities in Korean adults.
      METHODS: A total of 14,301 adults (5715 men and 8586 women) aged >=30 years with
      no diagnosis and treatment for diabetes, hypertension, or dyslipidemia were
      selected from the 2008 to 2012 Korea National Health and Nutrition Examination
      Survey data. From the 24-hour recall data, dietary carbohydrate and fat intakes
      were estimated. Multivariate logistic regression was used to estimate odds ratios
      for lipid abnormalities, that is, elevated total cholesterol (TC), low HDL-C,
      high TC to HDL-C ratio, elevated non-HDL-C, elevated LDL cholesterol (LDL-C), and
      elevated TG across quintiles of dietary carbohydrate and fat intakes. RESULTS:
      Percentage of energy from carbohydrate was positively associated with elevated TG
      and low HDL-C but inversely associated with elevated TC and elevated LDL-C in
      both men and women. Energy-adjusted carbohydrate intake also showed a positive
      association with low HDL-C. Dietary fat intakes had the opposite associations
      with lipid abnormalities than results for carbohydrate. CONCLUSION: High
      carbohydrate diet is undesirable with regard to increased TG and reduced HDL-C
      despite the benefit for LDL-C. Dietary strategies emphasizing appropriate
      macronutrient intakes by the type of lipid abnormalities are recommended for the
      prevention of cardiovascular disease in Korean adults.

PMID- 28502491
TI  - A novel frameshift mutation in the lipoprotein lipase gene is rescued by
      alternative messenger RNA splicing.
AB  - BACKGROUND: Type I hyperlipoproteinemia, manifesting as chylomicronemia and
      severe hypertriglyceridemia, is a rare autosomal recessive disorder usually
      caused by mutations in the lipoprotein lipase gene (LPL). OBJECTIVE: We sought to
      determine whether mutations in LPL could explain the clinical indications of a
      patient presenting with pancreatitis and hypertriglyceridemia. METHODS: Coding
      regions of LPL were amplified by polymerase chain reaction and analyzed by
      nucleotide sequencing. The LPL messenger RNA transcript was also analyzed to
      investigate whether alternative splicing was occurring. RESULTS: The patient was
      homozygous for the mutation c.767_768insTAAATATT in exon 5 of the LPL gene. This
      mutation is predicted to result in either a truncated nonfunctional LPL, or
      alternatively a new 5' donor splice site may be used, resulting in a full-length
      LPL with an in-frame deletion of 3 amino acids. Analysis of messenger RNA from
      the patient showed that the new splice site is used in vivo. CONCLUSION:
      Homozygosity for a mutation in the LPL gene was consistent with the clinical
      findings. Use of the new splice site created by the insertion mutation rescues an
      otherwise damaging frameshift mutation, resulting in expression of an almost full
      length LPL that is predicted to be partially functional. The patient therefore
      has a less severe form of type I hyperlipoproteinemia than would be expected if
      she lacked any functional LPL.

PMID- 28502490
TI  - Cardiovascular disease prevalence and insulin resistance in the Kyushu-Okinawa
      Population Study and the Framingham Offspring Study.
AB  - BACKGROUND: Age-adjusted cardiovascular disease (CVD) prevalence rates are
      significantly lower in Japan than in the United States. OBJECTIVE: Our aim was to
      compare CVD risk in participants in Fukuoka and Framingham. METHODS: We measured
      glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol (LDL-C), small dense LDL-C, and triglycerides in men and women from
      Fukuoka (n = 1108), and age (median, 53 years) and gender-matched subjects from
      Framingham (n = 1101). Blood pressure, body mass index, use of medications, and
      history of CVD were also assessed. RESULTS: CVD prevalence rates were more than 6
      fold higher in Framingham men and women than their Fukuoka counterparts (P <
      .001). Median body mass index, LDL-C, insulin levels, and insulin resistance
      assessment in Fukuoka men and women were significantly (P < .01) lower than in
      Framingham; however, diabetes prevalence in Fukuoka men was significantly (P <
      .01) higher than in Framingham men, whereas female rates were similar, as were
      levels of systolic blood pressure. High-density lipoprotein cholesterol and
      surprisingly small dense LDL-C levels were significantly (P < .001) higher in
      Fukuoka than in Framingham. Standard risk factors do not account for the large
      differences in CVD prevalence rates between the 2 populations, and population
      differences in insulin resistance may explain some of these differences.
      CONCLUSIONS: Our data are consistent with the concept that the CVD prevalence
      rate in a Japanese population is much lower than those observed in the United
      States, and that these differences cannot be explained by standard CVD risk
      factors, but may relate to marked population differences in insulin resistance.

PMID- 28502492
TI  - Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) has reported to be a major public
      health crisis in China. OBJECTIVE: We examined the incidence of new T2DM over 4
      years for association of clinical factors and lipids with development of T2DM in
      a community-based population. METHODS: We included 923 Chinese subjects who
      participated in community-organized health checkout in both 2009 and 2013. Health
      history was collected; physical examination was performed; biochemistry, lipids,
      and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and
      included in the analysis. Unadjusted and adjusted logistic regression models were
      used to estimate the effects of clinical factors and biomarkers on the risk of
      new T2DM. RESULTS: Of 819 subjects without T2DM in 2009, 65 were identified as
      T2DM in 2013, 8% over 4 years. These 65 subjects, compared with those 754 without
      new T2DM, were older, more likely to be male and smokers. They had higher body
      mass index (BMI), fasting glucose, blood pressure and triglycerides, and lower
      levels of high-density lipoprotein-cholesterol and apolipoprotein A1 (ApoA1).
      Multivariate logistic regression identified larger BMI (odds ratio [OR] = 1.7;
      95% confidence interval [CI], 1.22-2.39, P = .002), higher fasting glucose levels
      (OR = 4.2, 95% CI, 2.90-6.19, P < .001), and low levels of ApoA1 (OR = 0.51, 95%
      CI 0.33-0.76, P = .002) were independently associated with new T2DM. Furthermore,
      receiver operating characteristics curves for multivariate models for new T2DM
      showed that area under the curve improved from 0.87 to 0.89 when adding ApoA1 to
      the Framingham Diabetes Risk Scoring Model and from 0.85 to 0.89 when adding
      ApoA1 to a 4-variable (age, BMI, glucose, and triglycerides) Chinese model.
      CONCLUSIONS: There is a high incidence of new T2DM at 8% over 4 years among
      Chinese. Larger BMI, higher glucose levels, and lower levels of ApoA1 are
      significantly and independently associated with new T2DM. Lower ApoA1 improves
      the risk prediction of new type 2 diabetes when it was added to the existing risk
      models.

PMID- 28502493
TI  - The effect of maximal vs submaximal exertion on postprandial lipid levels in
      individuals with and without coronary heart disease.
AB  - BACKGROUND: Decisions about fat consumption and levels of physical activity are
      among the everyday choices we make in life and risk of coronary heart disease
      (CHD) can be affected by those choices. OBJECTIVE: The purpose of this study was
      to investigate the influence of a standard fat load combined with physical
      exertion of different intensities on the plasma lipid profile of CHD patients and
      CHD-free individuals. METHODS: This study looked at the influence of different
      intensities of physical exercise on postprandial lipid metabolism in 20 healthy
      men and 36 men with diagnosis of CHD. Venous blood samples were obtained after
      overnight fasting, 3 hours after standard fat load (before the physical load),
      and immediately after maximal or submaximal physical exercise on bicycle
      ergometer. RESULTS: After fat load total cholesterol (TC) concentration did not
      change in either group. However, after the addition of maximal exercise, TC,
      triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and
      apolipoprotein (Apo) B increased significantly (P < .01) in both groups. After
      fat load and maximal exercise, there was no change in high-density lipoprotein
      cholesterol (HDL-C) in healthy men, but in men with CHD, HDL-C fell significantly
      (P < .01); and Apo AI rose in healthy men (P < .01) but dropped significantly (P
      < .01) in men with CHD. Submaximal physical exercise (60% of max VO2 load for 40
      minutes) after fat load decreased TG level in CHD patients (P < .01) and improved
      other lipid parameters in both groups significantly (?LDL-C, ?HDL-C, ?Apo AI,
      ?Apo B, P < .01). We observed a worsening of physical work capacity in men with
      CHD (significant reduction of duration and total amount of work performed,
      maximal VO2, oxygen pulse), during maximal stress test performed 3 hours after
      fat load. There was a doubling of the number of abnormal stress test results (P <
      .01). Healthy persons showed an increase in respiratory parameters (ventilation,
      CO2 production, maximal VO2, and oxygen pulse), but no significant change was
      found in work capacity. Thus, maximal physical exercise produced atherogenic
      blood lipid changes (increased TC, increased LDL-C, increased TG, increased Apo
      B, P < .01) in men with CHD and in healthy men; however, individuals with CHD
      also demonstrated a significant decrease in HDL-C and Apo AI (P < .01). In
      contrast, the submaximal physical load improved postprandial lipid changes in
      both healthy men and men with CHD. CONCLUSIONS: This study demonstrates that
      moderate exercise is beneficial in improving postprandial lipid abnormalities in
      both CHD and CHD-free subjects after fatty meal preload. In addition, maximal
      exercise demonstrated evidence of increase of lipid abnormalities in both CHD and
      CHD-free individuals under similar conditions of fatty meal preload.

PMID- 28502494
TI  - Association of fasting triglyceride concentration and postprandial triglyceride
      response with the carotid intima-media thickness in the middle aged: The
      Netherlands Epidemiology of Obesity study.
AB  - BACKGROUND: People are in a postprandial state for the majority of the day,
      postprandial triglyceride (TG) response may be more important in the etiology of
      atherosclerosis than fasting TGs. OBJECTIVE: The objective of the study was to
      investigate the associations of fasting TG concentration (TGc) and postprandial
      TG response after a meal challenge with subclinical atherosclerosis, measured by
      intima-media thickness (IMT) in a middle-aged population. METHODS: A total of
      5574 participants (57% women) with a mean (standard deviation [SD]) age of 56 (6)
      years were included in this cross-sectional analysis of baseline measurements of
      The Netherlands Epidemiology of Obesity study. Serum TGc was measured fasting and
      30 and 150 minutes after a liquid mixed meal, and the incremental area under the
      curve (TGiAUC) was calculated. With linear regression analyses, we calculated the
      differences in IMT with 95% confidence intervals, adjusted for confounding
      factors, and additionally for TGc or TGiAUC. RESULTS: Per SD of TGc (0.82
      mmol/L), IMT was 8.5 MUm (2.1, 14.9) greater after adjustment for TGiAUC and
      confounding factors. Per SD of TGiAUC (24.0 mmol/L * min), the difference in IMT
      was -1.7 MUm (-8.5, 5.0) after adjustment for fasting TG and confounding factors.
      CONCLUSIONS: The association between TG response after a mixed meal and IMT
      disappeared after adjusting for TGc. The association between fasting TG
      concentration and IMT persisted after adjustment for postprandial TG response.
      These findings imply that it is not useful to perform a meal challenge in
      cardiovascular risk stratification. Our results support use of fasting TGc
      instead of postprandial TG responses for cardiovascular risk stratification in
      clinical practice.

PMID- 28502495
TI  - Detection of common sequence variations of familial hypercholesterolemia in
      Taiwan using DNA mass spectrometry.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a heterogeneous autosomal
      dominant disease. The genetic heterogeneity of FH requires low-cost, high
      throughput, and rapid mutation detection technology to efficiently integrate
      genetic screening into clinical practice. OBJECTIVES: The aims of the study were
      to customize the MassARRAY assay to (1) establish an FH mutation assay panel,
      comprising known point mutations located on FH-causing genes and (2) test the
      feasibility of the assay for screening FH patients residing in Taiwan who fit the
      clinical criteria of FH diagnosis. METHODS: We designed a custom Agena iPLEX
      assay to detect 68 point mutations on FH-causing genes. First, the assay
      performance was verified by analyzing 180 previously sequenced subjects (120 with
      point mutations and 60 healthy controls), with the results being compared with
      those of Sanger DNA sequencing. Second, a blind study was carried out on 185 FH
      probands (44 definite FH and 141 probable/possible FH). RESULTS: In the first
      part of this study, only 1 discrepancy was found between the Agena iPLEX and
      Sanger sequencing genotyping results. In the blind study, a total of 62 probands
      with mutations were identified by both techniques. Five mutations were detected
      by Sanger sequencing assay only. The detection sensitivity and specificity rates
      of Agena iPLEX were 92.5% and 100%, respectively, in the blind study. The hands
      on time for the Agena iPLEX assay was around 1 day. CONCLUSIONS: The custom
      designed Agena iPLEX assay has high specificity and sensitivity for FH genetic
      screening. Considering its low cost, rapidity, and flexibility, the assay has
      great potential to be incorporated into FH screening in Taiwan.

PMID- 28502497
TI  - The 9p21.3 locus and cardiovascular risk in familial hypercholesterolemia.
AB  - BACKGROUND: Carrying a risk variant in the 9p21.3 locus represents one of the
      strongest genetic risk factors for atherosclerotic cardiovascular disease (ASCVD)
      in the general population. However, the effect of these polymorphisms in patients
      with familial hypercholesterolemia (FH) has never been studied. OBJECTIVE: The
      objective of this study was to investigate the association between the sentinel
      9p21.3 single nucleotide polymorphisms (SNP) rs1333047 and ASCVD susceptibility
      in FH subjects. METHODS: A total of 20,434 Caucasian patients with dyslipidemia
      were screened, of which 725 FH were included in this study. The risk allele (T)
      of the rs1333047 SNP has previously been shown to confer increased ASCVD risk
      compared with the control allele (A). RESULTS: In a model adjusted for
      traditional cardiovascular risk factors, carrying the risk allele was associated
      with a 42% increased ASCVD susceptibility per allele, according to an additive
      model (odds ratio = 1.42; 95% confidence interval, 1.05-1.91; P = .02). On
      average, 0.53 cardiovascular event was observed in AA carriers, compared with
      0.83 in the TT group (P = .02). The mean age of first ASCVD event was similar
      among the 3 variants. CONCLUSION: The 9p21.3 SNP rs1333047 SNP was associated
      with increased ASCVD in FH subjects. Genetic screening for this SNP could allow
      to identify very high risk FH patients, which could benefit from more aggressive
      ASCVD prevention.

PMID- 28502496
TI  - Minimal food effect for eicosapentaenoic acid and docosahexaenoic acid
      bioavailability from omega-3-acid ethyl esters with an Advanced Lipid
      TechnologiesTM (ALT(r))-based formulation.
AB  - BACKGROUND: The absorption of eicosapentaenoic acid (EPA; 20:5n-3) and
      docosahexaenoic acid (DHA; 22:6n-3) omega-3-acid ethyl esters (EEs) is influenced
      by food. There is a need for a formulation of EE that is less impacted by food
      effect. SC401 is a novel Advanced Lipid Technologies-based formulation of EPA-EE
      and DHA-EE. In the presence of an aqueous medium, Advanced Lipid Technologies
      forms stable micelles in situ independent of bile salt secretion. This effect is
      hypothesized to improve EPA-EE and DHA-EE bioavailability while it helps mitigate
      the food effect associated with their consumption. OBJECTIVE: The aim of the
      article was to assess the effect of food on the bioavailability of DHA and EPA
      after a single oral dose of 1530 mg omega-3 fatty acids EE (SC401) in 24 healthy
      subjects under fasted and low-fat (9% of total calories from fat) and high-fat
      (50% of total calories from fat) meal conditions. METHODS: This was a randomized,
      open-label, single-dose, 3-period, 3-way crossover study. Blood samples for
      pharmacokinetic analyses were taken at predose and at 0.5, 1, 2, 3, 3.5, 4, 4.5,
      5, 5.5, 6, 6.5, 7, 8, 10, 12 and 24 hours postdose. To assess the safety of the
      intervention, active monitoring of adverse events, physical examinations, vital
      signs, clinical laboratory assessments (chemistry, hematology, and urinalysis),
      and 12-lead electrocardiograms were conducted. RESULTS: SC401 showed high
      bioavailability of both EPA and DHA in fasted, low-fat meal, and high-fat meal
      conditions. No differences were found in SC401 DHA AUC0-t (t = 24 hours) among
      the 3 conditions (91.69% high-fat/fasted, 97.12% low-fat/fasted, and 105.92% low
      fat/high-fat; P > .05 in all cases). In contrast, SC401 EPA AUC0-t was affected
      by food intake (179.06% high-fat/fasted, P < .0001; 150.05% low-fat/fasted, P <
      .0001) and the amount of fat taken with SC401 (83.80% low-fat/high-fat; P =
      .0009). SC401 was safe and well tolerated. CONCLUSIONS: A single dose of SC401
      resulted in high levels of EPA and DHA total lipids in plasma in fasting and fed
      conditions. SC401 overcame the food effect for DHA and partially ameliorated it
      for EPA. SC401 represents a convenient option for treatment of severe
      hypertriglyceridemia, especially for patients under a restricted intake of
      dietary fat.

PMID- 28502499
TI  - Effects of statin therapy on cerebrovascular and renal outcomes in patients with
      predialysis advanced chronic kidney disease and dyslipidemia.
AB  - BACKGROUND: Treatment with statin may be beneficial for patients with chronic
      kidney disease (CKD). However, the debate over the clinical importance of statin
      in patients with predialysis advanced CKD remains unresolved. OBJECTIVES: The
      objective of the article was to evaluate the effect of statin on mortality,
      cerebrovascular, and renal outcomes in patients with predialysis advanced CKD and
      dyslipidemia. METHODS: Data on predialysis advanced CKD patients were retrieved
      from the National Health Insurance Research Database based on the guidelines for
      prescribing regular erythropoietin-stimulating agent in CKD patients. Patients
      with dyslipidemia were further selected and divided into 2 groups by their statin
      use after the prescribed erythropoietin-stimulating agent. All-cause mortality
      and cerebrovascular and renal outcomes were analyzed after propensity score
      matching. RESULTS: There were 2016 and 14,412 patients in the statin and
      nonstatin groups. Their average follow-up periods were 3.7 and 3.0 years,
      respectively. After 1:2 propensity score matching, the annual all-cause mortality
      rate was higher in the nonstatin than in the statin group (143.99 vs 109.50 per
      1000 person-years; P < .001; hazard ratio: 0.73; 95% confidence interval: 0.68
      080). The annual risk of ischemic stroke (P = .186) and intracranial hemorrhage
      (P = .322) were not significantly different between the 2 groups. The nonstatin
      group had a higher risk of dialysis than the statin group (1269.45 vs 1095.00 per
      1000 person-years; P = .002). Adverse events were not significant between the 2
      groups. CONCLUSIONS: Statins may reduce the all-cause mortality and reduced the
      risk of dialysis in patients with predialysis advanced CKD and dyslipidemia.
      However, statins have no impact on ischemic-hemorrhage stroke.

PMID- 28502498
TI  - Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden,
      and vessel remodeling in heterozygous familial hypercholesterolemia.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important
      contributor to low-density lipoprotein metabolism in heterozygous familial
      hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9
      circulates as mature and furin-cleaved forms, which differ in its biological
      activity. However, it remains to be elucidated whether each PCSK9 subtype has
      different atherogenic properties. OBJECTIVE: To investigate the association of
      each PCSK9 subtype with coronary atherosclerosis in HeFH. METHODS: About 204
      nonculprit segments in 138 HeFH subjects with coronary artery disease were
      evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and
      total concentration of PCSK9 subtypes were measured by using enzyme-linked
      immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9
      values with intravascular ultrasound measures was investigated. RESULTS: Mature
      PCSK9 level was positively associated with percent atheroma volume (PAV: r =
      0.78, P = .003). Despite extensive atheroma under a higher mature PCSK9 level,
      vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78).
      These responses resulted in smaller lumen volume, which was negatively correlated
      to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no
      significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total
      PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level
      independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11
      1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level
      <2.6 mmol/L, greater PAV was still observed in association with an elevated
      mature PCSK9 level (P = .003). CONCLUSIONS: Mature PCSK9 associated with atheroma
      volume and impaired vessel remodeling in HeFH patients with coronary artery
      disease. These findings suggest the potential role of mature PCSK9 in propagation
      of coronary atherosclerosis in HeFH.

PMID- 28502500
TI  - The association between dietary cholesterol intake and subclinical
      atherosclerosis in Korean adults: The Kangbuk Samsung Health Study.
AB  - BACKGROUND: The Scientific Report of the Dietary Guidelines Advisory Committee
      (2015) concluded that restriction of dietary cholesterol is unnecessary in most
      adults for the prevention of cardiovascular disease. OBJECTIVE: We aimed to
      assess the risk for subclinical atherosclerosis according to coronary artery
      calcium score (CACS), based on dietary cholesterol intake in apparently healthy
      Korean adults. METHODS: This was a cross-sectional study performed in 30,068
      participants (mean age 40.8 years; 84.5% men) in a health screening program in
      Korea. The data were collected from 2001 to 2013 and analyzed in 2015. Total
      energy intake and dietary cholesterol intake were assessed with a food frequency
      questionnaire. The participants were stratified according to quartile of dietary
      cholesterol intake. CACS was measured by multi-detector computed tomography.
      Lipid profiles were measured, and the participants were divided into 6 groups
      according to low-density lipoprotein cholesterol (LDL-C) level: <70, 70 to 99,
      100 to 129, 130 to 159, 160 to 189, and >=190 mg/dL. RESULTS: The presence of
      coronary artery calcification was defined as CACS>0. Dietary cholesterol intake
      did not correlate with mean value of serum LDL-C level. For both genders, the
      odds ratio for coronary artery calcification was not significantly greater with
      greater amounts of dietary cholesterol (as assessed by quartile). The risk for
      coronary artery calcification was not higher in subjects with LDL-C 70-129 mg/dL
      compared with those with LDL-C < 70 mg/dL; however, the risk was significantly
      greater in subjects with LDL-C >= 130 mg/dL compared with those with LDL-C < 70
      mg/dL. CONCLUSIONS: Dietary cholesterol intake did not have an association with
      LDL-C level or with risk for coronary artery calcification in apparently healthy
      Korean adults. The results have to be translated with consideration of limitation
      of population-based studies.

PMID- 28502501
TI  - Apolipoprotein B vs non-high-density lipoprotein cholesterol: Association with
      endothelial hemostatic markers and carotid intima-media thickness.
AB  - BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein
      cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for
      lipid-lowering therapy, which correlate more strongly with cardiovascular events
      than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross
      sectional study was to evaluate the differences in plasma levels of plasminogen
      activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial
      hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic
      marker for atherosclerotic vascular disease among dyslipidemic individuals with
      apoB levels higher, estimated or lower based on regression equation of apoB vs
      non-HDL-C. METHODS: A total of 594 dyslipidemic subjects without atherosclerotic
      manifestation were divided into 3 groups (according to tertiles of apoB levels
      above, within, and below the line of identity): H-apoB (n = 200), E-apoB (n =
      194), and L-apoB (n = 200). PAI-1, vWF, C-IMT and lipids, anthropometric
      parameters, markers of insulin resistance, and inflammation were measured.
      Differences in variables between groups were analyzed using analysis of variance.
      RESULTS: There was a strong association between apoB and non-HDL-C. The
      correlations of apoB and of non-HDL-C with markers of endothelial damage and C
      IMT were very similar. Despite these facts, individuals with higher apoB levels
      had significantly higher levels of PAI-1 compared with individuals with estimated
      (P < .05) or lower apoB (P < .001). There were no significant differences in vWF,
      C-IMT, markers of insulin resistance, obesity, and inflammation. CONCLUSION:
      Individuals with apoB higher than predicted by non-HDL-C had significantly higher
      levels of PAI-1, which may contribute to the increased risk of future
      atherothrombotic events.

PMID- 28502502
TI  - Dapagliflozin in patients with type II diabetes mellitus, with and without
      elevated triglyceride and reduced high-density lipoprotein cholesterol levels.
AB  - BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor
      that improves glycemic control in patients with type II diabetes mellitus (T2DM)
      by reducing renal glucose reabsorption. OBJECTIVE: The aim was to evaluate the
      lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM
      with/without baseline elevated triglyceride and reduced high-density lipoprotein
      (HDL) cholesterol levels. METHODS: This was a post hoc analysis of 10 phase 3,
      placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N =
      2164) administered for 24 weeks in patients with T2DM. Patients with elevated
      triglyceride (>=150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40
      mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included
      (group A). The reference group (group B) included patients who did not meet the
      defined lipid criteria. RESULTS: The effects of dapagliflozin on fasting lipid
      profiles were generally similar in the 2 lipid groups (ie, groups A and B) and,
      compared with placebo, were associated with minor increases in non-HDL
      cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on
      triglyceride levels were inconsistent. The incidence of adverse events
      (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume
      reduction, renal function, and hypoglycemia were similar in the 2 lipid groups.
      CONCLUSION: Patients with T2DM treated with dapagliflozin experienced minor
      changes in lipid levels; the changes were generally similar in the 2 lipid
      groups. The clinical significance of these changes in lipids is unclear,
      especially in view of the positive effects of dapagliflozin on other
      cardiovascular disease risk factors.

PMID- 28502503
TI  - The effects of vitamin D and omega-3 fatty acid co-supplementation on glycemic
      control and lipid concentrations in patients with gestational diabetes.
AB  - OBJECTIVE: This study was performed to evaluate the effects of vitamin D and
      omega-3 fatty acids co-supplementation on glucose metabolism and lipid
      concentrations in gestational diabetes (GDM) patients. METHODS: This randomized
      double-blind placebo-controlled clinical trial was done among 140 GDM patients.
      Participants were randomly divided into 4 groups to receive: (1) 1000 mg omega-3
      fatty acids containing 360 mg eicosapentaenoic acid and 240 mg docosahexaenoic
      acid (DHA) twice a day + vitamin D placebo (n = 35); (2) 50,000 IU vitamin D
      every 2 weeks + omega-3 fatty acids placebo (n = 35); (3) 50,000 IU vitamin D
      every 2 weeks + 1000 mg omega-3 fatty acids twice a day (n = 35), and (4) vitamin
      D placebo + omega-3 fatty acids placebo (n = 35) for 6 weeks. RESULTS: After 6
      weeks of intervention, patients who received combined vitamin D and omega-3 fatty
      acids supplements compared with vitamin D, omega-3 fatty acids, and placebo had
      significantly decreased fasting plasma glucose (-7.3 +/- 7.8, -6.9 +/- 6.6, -4.0
      +/- 2.5, and +1.0 +/- 11.4 mg/dL, respectively, P < .001), serum insulin levels (
      1.9 +/- 1.9, -1.3 +/- 6.3, -0.4 +/- 6.3, and +2.6 +/- 6.5 MUIU/mL, respectively,
      P = .005), homeostatic model of assessment for insulin resistance (-0.7 +/- 0.6, 
      0.5 +/- 1.4, -0.2 +/- 1.5, and +0.6 +/- 1.5, respectively, P < .001) and
      increased quantitative insulin sensitivity check index (+0.01 +/- 0.01, +0.008 +/
      0.02, +0.002 +/- 0.02, and -0.005 +/- 0.02, respectively, P = .001). In
      addition, changes in serum triglycerides (-8.2 +/- 41.0, +7.6 +/- 31.5, +3.6 +/-
      29.9, and +20.1 +/- 29.6 mg/dL, respectively, P = .006) and very low-density
      lipoprotein cholesterol (-1.6 +/- 8.2, +1.5 +/- 6.3, +0.8 +/- 6.0, and +4.0 +/-
      5.9 mg/dL, respectively, P = .006) in the vitamin D plus omega-3 fatty acids
      group were significantly different from the changes in these indicators in the
      vitamin D, omega-3 fatty acids, and placebo groups. CONCLUSION: Overall, vitamin
      D and omega-3 fatty acids co-supplementation for 6 weeks among GDM patients had
      beneficial effects on fasting plasma glucose, serum insulin levels, homeostatic
      model of assessment for insulin resistance, quantitative insulin sensitivity
      check index, serum triglycerides, and very low-density lipoprotein cholesterol
      levels.

PMID- 28502504
TI  - High-density lipoproteins and adrenal steroidogenesis: A population-based study.
AB  - BACKGROUND: Cholesterol trafficked within plasma lipoproteins, in particular high
      density lipoproteins (HDL), may represent an important source of cholesterol that
      is required for adrenal steroidogenesis. Based on a urinary gas chromatography
      method, compromised adrenal function has been suggested in men but not in women
      with (genetically determined) low plasma HDL-cholesterol (HDL-C). OBJECTIVE: The
      objective of the article was to examine the extent to which glucocorticoid
      production relates to HDL-C in a population-based cohort. METHODS: A total of 240
      subjects (120 men and 120 women, aged 20-79 years) without relevant comorbidities
      were recruited from the general population. Glucocorticoid metabolites were
      measured by gas chromatography with tandem mass spectrometric detection in 24
      hour urine collections to estimate total glucocorticoid production (TGP). Fasting
      plasma (apo)lipoproteins were assayed by routine methods. RESULTS: TGP was not
      decreased but tended to be increased in subjects with low HDL-C (NCEP-ATPIII
      criteria; P = .094). In univariate analysis, TPG was correlated inversely with
      HDL-C (r = -0.353, P < .001) and apoA-I (r = -0.263, P = .01). Multivariable
      linear regression analysis demonstrated that TGP was still inversely related to
      HDL-C (beta = -0.145, P = .019) or alternatively to low HDL-C (beta = -0.129, P =
      .013) taking age, sex, current smoking, and other metabolic syndrome components
      into account. CONCLUSION: In this population-based study, urinary glucocorticoid
      metabolite excretion was inversely associated with HDL-C. We found no evidence
      for an attenuated adrenal function in men and women with low HDL-C.

PMID- 28502506
TI  - Attitudes and actions: A survey to assess statin use among Finnish patients with
      increased risk for cardiovascular events.
AB  - BACKGROUND: Statins are the first-line treatment for lowering serum cholesterol
      and preventing coronary artery disease (CAD). Patients who fail to comply with
      the prescribed statin treatment face a markedly increased risk for cardiovascular
      events. OBJECTIVE: The aim of the article was to study the subjective factors,
      which modulate persistence with and adherence to statin therapy among Finnish
      patients at high risk for cardiovascular events. METHODS: A total of 1022 Finnish
      adults diagnosed with CAD, diabetes, hypertension, or severe hereditary
      dyslipidemia completed an electronic questionnaire survey during a visit in 1 of
      the 84 community pharmacies participating in the study. RESULTS: Thirty-four
      percent of the survey respondents were diagnosed with CAD or severe hereditary
      dyslipidemia and 82% were current or former statin users. Prevalence of
      nonpersistence with statin therapy was 15% among CAD patients and 17% among
      respondents without the diagnosis. Most of the nonpersistent statin users had
      discontinued the medication without consultation of a physician. None of the
      studied sociodemographic background factors were associated with persistence with
      statin therapy. Instead, experienced adverse effects, fear of adverse effects,
      perceived lack of need, and difficulties in use of a statin emerged as powerful
      predictors of nonpersistence. Awareness of treatment goals was low, and
      strikingly, public discussion about adverse effects of statins had induced nearly
      every third discontinuation of statin treatment. CONCLUSION: Several subjective,
      potentially modifiable reasons for nonpersistence were identified from the
      patient perspective. Improved utilization of patient-centered approaches in
      pharmacologic management of cardiovascular risks is necessary to improve
      adherence, and ultimately, treatment outcomes.

PMID- 28502505
TI  - Lysosomal acid lipase deficiency: A hidden disease among cohorts of familial
      hypercholesterolemia?
AB  - BACKGROUND: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive
      disorder and an unrecognized cause of dyslipidemia. Patients usually present with
      dyslipidemia and altered liver function and mutations in LIPA gene are the
      underlying cause of LALD. OBJECTIVE: The aim of this study was to investigate
      LALD in individuals with severe dyslipidemia and/or liver steatosis. METHODS:
      Coding, splice regions, and promoter region of LIPA were sequenced by Sanger
      sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH)
      patients (n = 492) and in a population sample comprising individuals with several
      types of dyslipidemia and/or liver steatosis (n = 258). RESULTS: This study led
      to the identification of LALD in 4 children referred to the Portuguese FH Study,
      all with a clinical diagnosis of FH. Mild liver dysfunction was present at the
      age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults
      at the time of referral have been identified with LALD. CONCLUSION: LALD is a
      life-threatening disorder, and early identification is crucial for the
      implementation of specific treatment to avoid premature mortality. FH cohorts
      should be investigated to identify possible LALD patients, who will need
      appropriate treatment. These results highlight the importance of correctly
      identifying the etiology of the dyslipidemia.

PMID- 28502507
TI  - Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein
      distribution in obese human subjects.
AB  - BACKGROUND: Elevated apolipoprotein C-III (apoC-III) has been postulated to
      contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant
      states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL)
      metabolism. Bariatric surgery is associated with improvements of several obesity
      associated metabolic abnormalities, including a reduction in plasma triglycerides
      (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C).
      OBJECTIVES: We investigated the specific effect of bariatric surgery on apoC-III
      concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile
      parameters evolution. METHODS: A total of 132 obese subjects undergoing bariatric
      surgery, gastric bypass (n = 61) or sleeve gastrectomy (n = 71), were studied 1
      month before surgery and 6 and 12 months after surgery. RESULTS: Plasma apoC-III,
      non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after
      surgery and strongly associated with reduction in plasma TG. This decrease was
      accompanied by a redistribution of apoC-III from TRL to HDL fractions. In
      multivariate analysis, plasma apoC-III was the strongest predictor of TG
      reduction after surgery, and the increase of HDL-C was positively associated with
      plasma adiponectin and negatively with body mass index. CONCLUSION: Marked
      reduction of apoC-III and changes in its distribution between TRL and HDL
      consistent with a better lipid profile are achieved in obese patients after
      bariatric surgery. These apoC-III beneficial modifications may have implications
      in dyslipidemia improvement and contribute to cardiovascular risk reduction after
      surgery.

PMID- 28502508
TI  - Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant
      hypercholesterolemia.
AB  - BACKGROUND: Patients with autosomal dominant hypercholesterolemia (ADH), caused
      by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B
      (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are
      characterized by high low-density lipoprotein cholesterol levels and in some
      studies also high lipoprotein(a) (Lp(a)) levels were observed. The question
      remains whether this effect on Lp(a) levels is gene-dose-dependent in individuals
      with either 0, 1, or 2 LDLR or APOB mutations. OBJECTIVE: We set out to study
      whether Lp(a) levels differ among bi-allelic ADH mutation carriers, and their
      relatives, in the Netherlands. METHODS: Bi-allelic ADH mutation carriers were
      identified in the database of the national referral laboratory for DNA
      diagnostics of inherited dyslipidemias. Family members were invited by the index
      cases to participate. Clinical parameters and Lp(a) levels were measured in bi
      allelic ADH mutation carriers and their heterozygous and unaffected relatives.
      RESULTS: We included a total of 119 individuals; 34 bi-allelic ADH mutation
      carriers (20 homozygous/compound heterozygous LDLR mutation carriers (HoFH), 2
      homozygous APOB mutation carriers (HoFDB), and 12 double heterozygotes for an
      LDLR and APOB mutation), 63 mono-allelic ADH mutation carriers (50 heterozygous
      LDLR [HeFH], 13 heterozygous APOB [HeFDB] mutation carriers), and 22 unaffected
      family members. Median Lp(a) levels in unaffected relatives, HeFH, and HoFH
      patients were 19.9 (11.1-41.5), 24.4 (5.9-70.6), and 47.3 (14.9-111.7) mg/dL,
      respectively (P = .150 for gene-dose dependency). Median Lp(a) levels in HeFDB
      and HoFDB patients were 50.3 (18.7-120.9) and 205.5 (no interquartile range
      calculated), respectively (P = .012 for gene-dose-dependency). Double
      heterozygous carriers of LDLR and APOB mutations had median Lp(a) levels of 27.0
      (23.5-45.0), which did not significantly differ from HoFH and HoFDB patients (P =
      .730 and .340, respectively). CONCLUSION: A (trend toward) increased plasma Lp(a)
      levels in homozygous ADH patients compared with both heterozygous ADH and
      unaffected relatives was observed. Whether increased Lp(a) levels in homozygous
      ADH patients add to the increased cardiovascular disease risk and whether this
      risk can be reduced by therapies that lower both low-density lipoprotein
      cholesterol and Lp(a) levels remains to be elucidated.

PMID- 28502509
TI  - The heterozygous N291S mutation in the lipoprotein lipase gene impairs whole-body
      insulin sensitivity and affects a distinct set of plasma metabolites in humans.
AB  - BACKGROUND: Mutations in the lipoprotein lipase gene causing decreased
      lipoprotein lipase activity are associated with surrogate markers of insulin
      resistance and the metabolic syndrome in humans. OBJECTIVE: We investigated the
      hypothesis that a heterozygous lipoprotein lipase mutation (N291S) induces whole
      body insulin resistance and alterations in the plasma metabolome. METHODS: In 6
      carriers of a heterozygous lipoprotein lipase mutation (N291S) and 11 age-matched
      and weight-matched healthy controls, we examined insulin sensitivity and
      substrate metabolism by euglycemic-hyperinsulinemic clamps combined with indirect
      calorimetry. Plasma samples were taken before and after the clamp (4 hours of
      physiological hyperinsulinemia), and metabolites were measured enzymatically or
      by gas chromatography-mass spectrometry. RESULTS: Compared with healthy controls,
      heterozygous carriers of a defective lipoprotein lipase allele had elevated
      fasting plasma levels triglycerides (P < .006), and markedly impaired insulin
      stimulated glucose disposal rates (P < .024) and nonoxidative glucose metabolism
      (P < .015). Plasma metabolite profiling demonstrated lower circulating levels of
      pyruvic acid and alpha-tocopherol in the N291S carriers than in controls both
      before and after stimulation with insulin (all >1.5-fold change and P < .05).
      CONCLUSION: Heterozygous carriers with a defective lipoprotein lipase allele are
      less insulin sensitive and have increased plasma levels of nonesterified fatty
      acids and triglycerides. The heterozygous N291S carriers also have a distinct
      plasma metabolomic signature, which may serve as a diagnostic tool for deficient
      lipoprotein lipase activity and as a marker of lipid-induced insulin resistance.

PMID- 28502510
TI  - Preliminary spectrum of genetic variants in familial hypercholesterolemia in
      Argentina.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder
      characterized by elevated low-density lipoprotein cholesterol and early
      cardiovascular disease. As cardiovascular disease is a leading cause of mortality
      in Argentina, early identification of patients with FH is of great public health
      importance. OBJECTIVE: The aim of our study was to identify families with FH and
      to approximate to the characterization of the genetic spectrum mutations of FH in
      Argentina. METHODS: Thirty-three not related index cases were selected with
      clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex
      ligation-dependent probe amplification, and bioinformatics tools. RESULTS: Twenty
      genetic variants were identified among 24 cases (73%), 95% on the low-density
      lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were
      novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and
      c.1895A>T p.(Asn632Ile); the bioinformatics' analysis revealed clear
      destabilizing effects for 2 of them. The exon 14 presented the highest number of
      variants (32%). Four variants were observed in more than 1 case and the c.2043C>A
      p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound
      heterozygotes, and 1 double heterozygote were identified. CONCLUSION: This study
      characterizes for the first time in Argentina genetic variants associated with FH
      and suggest that the allelic heterogeneity of the FH in the country could have 1
      relative common low-density lipoprotein receptor mutation. This knowledge is
      important for the genotype-phenotype correlation and for optimizing both
      cholesterol-lowering therapies and mutational analysis protocols. In addition,
      these data contribute to the understanding of the molecular basis of FH in
      Argentina.

PMID- 28502511
TI  - Functional analysis of new 3' untranslated regions genetic variants in genes
      associated with genetic hypercholesterolemias.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is the best-described autosomal
      dominant genetic hypercholesterolemia (GH). Mutations in candidate genes can
      explain a high proportion of FH cases, but for many, no causative mutations are
      detected (designed non-FG-GH), suggesting the existence of additional genetic
      variants associated with the disease. OBJECTIVE: We aimed to identify new single
      nucleotide variants (SNVs) located at the 3' untranslated regions (3'UTRs) of the
      low-density lipoprotein receptor, low-density lipoprotein receptor-related
      protein-associated protein 1, ATP-binding cassette sub-family G member 5, and
      sterol regulatory element-binding protein 2 genes in non-FH-GH individuals and
      investigated whether the association of these SNVs with non-FH-GH could be
      explained by changes in the affinity of regulatory microRNAs (miRNA) targeting
      the sequences modified by the SNVs. METHODS: The study includes probands with non
      FH-GH attending 2 lipid clinics in Spain. We performed functional analyses of
      selected variants using a luciferase reporter system. Through in silico target
      prediction tools, we identified miRNAs, which binding to the 3'UTR could be
      affected by the presence of specific SNVs. We used analogs and inhibitors of
      these miRNAs to test this possibility. RESULTS: We identified 11 new SNVs showing
      significant association with non-FH-GH. We show that the presence of 4 of these
      SNVs leads to significant changes in the transcriptional levels of the reporter
      gene. Through mechanistic analysis, we identified 2 miRNAs (miR-27a and miR-133
      3p) targeting the 3'UTR of sterol regulatory element-binding protein 2 and an
      additional miRNA (miR-92a) targeting the 3'UTR of low-density lipoprotein
      receptor-related protein-associated protein 1. CONCLUSION: Our findings reveal
      novel regulatory links between certain miRNAs and key genes regulating
      cholesterol homeostasis. They also highlight the potential of miRNAs as
      therapeutic targets for the treatment of FH.

PMID- 28502513
TI  - Relationship between noninvasive scores of nonalcoholic fatty liver disease and
      nuclear magnetic resonance lipoprotein abnormalities: A focus on atherogenic
      dyslipidemia.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging, highly
      prevalent, cardiovascular risk factor, and lipoprotein proatherogenic
      disturbances likely explain a large part of this risk. However, information
      regarding associations between detailed nuclear magnetic resonance (NMR)
      lipoprotein changes and noninvasive NAFLD scores is lacking. OBJECTIVE: The
      objective of the study was to investigate the NMR-assessed atherogenic
      lipoprotein profile according to noninvasive NAFLD status. METHODS: Lipoprotein
      profiles by NMR spectroscopy and NAFLD status by fatty liver index (FLI) and
      Gholam's models. RESULTS: We assessed 173 participants (55% males), mean age 60.8
      +/- 7.8 years, 87% overweight/obese, 53% with diabetes. An FLI <30, 30 to 60, and
      >60 was found in 32, 50, and 91 participants, respectively. Individuals with FLI
      >60 had lower high-density lipoprotein (HDL)-cholesterol (P < .001), higher
      triglyceride (P < .001), and similar non-HDL-cholesterol (P = .912)
      concentrations. In NMR analysis, FLI was related with very-low-density
      lipoprotein (VLDL) and HDL parameters in a dose-dependent manner. VLDL particle
      number (P < .001) and VLDL size (39.1 +/- 0.99, 39.7 +/- 0.96, 40.8 +/- 1.19 nm,
      P < .001) increased with increased FLI (<30, 30-60, and >60, respectively).
      Conversely, although total HDL particle number did not differ by FLI (P = .377),
      larger HDL particles (P < .001), amount of cholesterol within HDL particles (P <
      .001), and HDL size (median [p25-p75]: 8.23 [8.08-8.41], 8.12 [8.03-8.29], 8.04
      [7.93-8.16] nm, P < .001) decreased as FLI increased. FLI >60 (vs <60) was
      associated with a higher proportion of small LDL particles (P = .010) and lower
      LDL size (19.85 +/- 0.34 vs 19.98 +/- 0.25 nm; P = .005). Similar findings were
      found for Gholam's model. CONCLUSION: Simple and noninvasive NAFLD scores are
      useful to detect many of the proatherogenic changes (especially in VLDL and HDL),
      beyond conventional lipids parameters that are common in individuals with this
      high-risk condition.

PMID- 28502512
TI  - Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with
      generalized lipodystrophy.
AB  - BACKGROUND: Reduced triglyceride clearance due to impaired lipoprotein lipase
      mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy.
      Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of
      triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4
      levels are altered in lipodystrophy and the effects of leptin replacement on
      these ANGPTLs are unknown. OBJECTIVE: To examine if ANGPTL3/4 levels are elevated
      in patients with generalized lipodystrophy and assess the effects of leptin
      replacement on these ANGPTLs. METHODS: Preleptin treatment plasma levels of
      ANGPTLs in patients with generalized lipodystrophy (n = 22) were compared with
      healthy controls (n = 39) using a post hoc case-control study design. In a
      prospective open-label study, we studied the effects of metreleptin therapy (16
      32 weeks) on plasma ANGPTL3/4 in patients with generalized lipodystrophy.
      RESULTS: Plasma ANGPTL3 (geometric mean [95% confidence interval]; 223 [182-275]
      vs 174 ng/mL [160-189], P = .02) but not ANGPTL4 levels (55 [37-81] vs 44 ng/mL
      [37-52], P = .26) were higher in patients with lipodystrophy compared with
      healthy controls. There was a significant decrease in total cholesterol,
      triglycerides, and glycosylated hemoglobin (A1C) levels following metreleptin
      therapy. After metreleptin, ANGPTL3 concentrations decreased significantly (223
      [182-275] vs 175 ng/mL [144-214], P = .01) with no change in ANGPTL4 (55 [37-81]
      vs 48 ng/mL [32-73], P = .11). CONCLUSIONS: These findings suggest that elevated
      plasma levels of ANGPTL3 in leptin-deficient states is attenuated with leptin
      therapy.

PMID- 28502514
TI  - Dyslipidemia, weight gain, and decreased growth velocity in a 14-year-old male.
AB  - A 14-year-old male was referred for dyslipidemia. His findings were consistent
      with metabolic syndrome. Although he lacked the typical physical appearance, his
      accelerated weight gain combined with a decreased linear growth velocity
      suggested Cushing syndrome. He was subsequently found to have adrenocorticotropic
      hormone-independent Cushing syndrome secondary to primary pigmented nodular
      adrenal disease without Carney Complex. After bilateral adrenalectomy, his lipid
      profile returned to normal. In this article, we discuss the role of
      glucocorticoids on lipid and lipoprotein metabolism.

PMID- 28502515
TI  - Lysosomal acid lipase deficiency in all siblings of the same parents.
AB  - We present 4 normal-weight sibling children with lysosomal acid lipase deficiency
      (LAL-D). LAL-D was considered in the differential diagnosis based on the absence
      of secondary causes and primary inherited traits for their marked hyperlipidemia,
      together with unexplained hepatic transaminase elevation. Residual lysosomal acid
      lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that
      the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case
      describes the unusual occurrence of all offspring from the same nonconsanguineous
      mother and father inheriting compound heterozygosity of a recessive trait and the
      identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights
      the collaborative effort between a lipidologist and gastroenterologist in
      developing a differential diagnosis leading to the confirmatory diagnosis of this
      rare, life-threatening disease. With the availability of an effective enzyme
      replacement therapy (sebelipase alfa), LAL-D should be entertained in the
      differential diagnosis of children, adolescents, and young adults with idiopathic
      hyperlipidemia and unexplained hepatic transaminase elevation.

PMID- 28502516
TI  - Detecting familial hypercholesterolemia: The Jack and the Beanstalk principle.
AB  - We report the case of an 8-year-old girl who was fortuitously diagnosed with
      familial hypercholesterolemia (FH) while being investigated for obesity. She had
      a fasting total cholesterol of 11.8 mmol/L and a low-density lipoprotein
      cholesterol level of 10.3 mmol/L. Her mother and maternal grandmother both had a
      history of hypercholesterolemia and had developed extensive xanthelasma
      palpebrarum from early adult life. Reverse cascade testing of first-degree and
      second-degree relatives diagnosed a further 6 individuals with FH within the
      family. We discuss the benefits of diagnosing FH in childhood, for the individual
      and the wider family network ("the beanstalk") and present the rationale for
      implementing a universal screening program for FH in childhood.

PMID- 28502517
TI  - Questions to the article by Boyer et al.

PMID- 28502518
TI  - [Management of acute exacerbations of chronic obstructive pulmonary disease
      (COPD). Guidelines from the Societe de Pneumologie de Langue Francaise
      (Argumentary)].

PMID- 28502519
TI  - [Blomia tropicalis: A house dust mite in the tropics].
AB  - INTRODUCTION: Blomia tropicalis is a mite that belongs to the superfamily of
      Glycyphagidae. Initially described as a storage mite, it is now considered as a
      house dust mite of tropical and sub-tropical areas. STATE OF THE ART:
      Sensitization to this mite is very common in South America and Southeast Asia.
      Epidemiological studies have also found sensitization to this mite in Africa and
      Central America. Blo t 5 is the major allergen of B. tropicalis. Co-sensitization
      to other house dust mites such as Dermatophagoides pteronyssinus (Der p) and
      Dermatophagoides farinae (Der f) is very common. Cross-reactivity has been
      described but recombinant allergens revealed by molecular biology techniques do
      not explain this cross-reactivity. Sensitization to B. tropicalis seems to begin
      at the age of 36 months, the incidence increases until adulthood, and decreases
      from the age of 50. The involvement of B. tropicalis in allergic rhinitis and
      asthma is well described. It is also implicated in other allergic diseases. Few
      studies have assessed the therapeutic strategies available against this mite but
      immunotherapy is widely used. PERSPECTIVES: Studies are needed to better
      understand the role of B. tropicalis in human diseases and to develop specific
      treatments.

PMID- 28502520
TI  - [Exploring the diaphragm: Ultrasound is essential].
AB  - The diaphragm is the muscle most implicated in breathing. Its morphological
      exploration usually depends on pulmonary radiography, fluoroscopy, CT-scanning
      and MRI. Its function is evaluated by the classical respiratory functional tests,
      the measurement of maximum inspiratory and expiratory pressures, the
      transdiaphragmatic pressure and even an electromyogram. Ultrasound is a technique
      still insufficiently used in respiratory medicine. It offers, however, many
      advantages: it is easy to implement, there is no irradiation, it is usable at the
      bedside, particularly when the patient is immobile or in intensive care. The
      results of the examination are immediately available. It allows morphological and
      dynamic study of each hemidiaphragm as well as providing invaluable information
      on the thoracic and subdiaphragmatic environment. Its field of exploration is
      extremely wide: raised hemidiaphragm, dyspnea following a stroke or a surgical
      procedure (thoracic or abdominal), road accident trauma, diagnosis and follow-up
      of a paresis or paralysis, evaluation of diaphragmatic mobility during the course
      of COPD (Chronic Obstructive Pulmonary Disease) and many other pathologies.
      Ultrasound is insufficiently used in pleural disease and even less so in the
      evaluation of the morphology and function of the diaphragm.

PMID- 28502521
TI  - [Extracorporeal life support in thoracic surgery: What are the indications and
      the pertinence?]
AB  - INTRODUCTION: In thoracic surgery, extracorporeal life support (ECLS)
      technologies are used in cases of severe and refractory respiratory failure or as
      intraoperative cardiorespiratory support. The objectives of this review are to
      describe the rationale of ECLS techniques, to review the pulmonary diseases
      potentially treated by ECLS, and finally to demonstrate the efficacy of ECLS,
      using recently published data from the literature, in order to practice evidence
      based medicine. STATE OF THE ART: ECLS technologies should only be undertaken in
      expert centers. ECLS allows a protective ventilatory strategy in severe ARDS. In
      the field of lung transplantation, ECLS may be used successfully as a bridge to
      transplantation, as intraoperative cardiorespiratory support or as a bridge to
      recovery in cases of severe primary graft dysfunction. In general thoracic
      surgery, ECLS technology seems to be safe and efficient as intraoperative
      respiratory support for tracheobronchial surgery or for severe respiratory
      insufficiency, without significant increase in perioperative risk. PERSPECTIVE:
      The indications for ECLS are going to increase. Future improvements both in
      scientific knowledge and bioengineering will improve the prognosis of patients
      treated with ECLS for respiratory failure. Multicenter randomized controlled
      trials will refine the indications for ECLS and improve the global care
      strategies for these patients. CONCLUSION: ECLS is an efficient therapeutic
      strategy that will improve the prognosis of patients suffering from, or exposed
      to, the risks of severe respiratory failure.

PMID- 28502522
TI  - Human herpesvirus 8-related diseases: Histopathologic diagnosis and disease
      mechanisms.
AB  - The emergence of HIV/AIDS more than three decades ago led to an increased
      incidence of diseases caused by HHV8 co-infection, particularly Kaposi sarcoma,
      primary effusion lymphoma, and multicentric Castleman disease. Over time, the
      development of highly effective AIDS therapies has resulted in a decreased
      incidence of HHV8-associated entities, which are now more commonly found in
      patients with undiagnosed and/or untreated AIDS. Due to their rarity, some of
      these diseases may be difficult to recognize without appropriate clinical
      information. This article provides an overview of HHV8-related disorders, with a
      focus on their morphologic and phenotypic features, and includes a brief overview
      of laboratory methods used to detect HHV8. Disease mechanisms by which the HHV8
      virion promotes tumorigenesis are also reviewed.

PMID- 28502523
TI  - Human immunodeficiency virus: Diagnostic approach.
AB  - First descriptions of acquired immunodeficiency syndrome appeared in 1981. Four
      years later the causative agent was cultured which lead to development and
      production of tests that helped healthcare providers to identify persons living
      with HIV. Currently, diagnosis of HIV is performed with fourth generation
      immunoassays (those that detect p24 antigen together with IgM and IgG antibodies
      to HIV-1 and -2) which if positive need to be followed by an assay that can
      differentiate between HIV-1 and HIV-2 viruses. The Western blot is no longer used
      to confirm HIV infections per CDC guidelines. In case there is a positive fourth
      generation assay but negative differentiation assay, nucleic acid testing for HIV
      1 should be performed. This algorithm allows for detection of acute infections.
      Alternatively, the World Health Organization has algorithms that use rapid
      testing for diagnosis of HIV infections. This review will describe the evolution
      of tests and diagnostic algorithms from the 1980s to the current state. Special
      situations regarding diagnosis will also be discussed.

PMID- 28502524
TI  - Human chorionic villous mesenchymal stem/stromal cells modify the effects of
      oxidative stress on endothelial cell functions.
AB  - Mesenchymal stem/stromal cells derived from chorionic villi of human term
      placentae (pMSCs) produce a unique combination of molecules, which modulate
      important cellular functions of their target cells while concurrently suppressing
      their immune responses. These properties make MSCs advantageous candidates for
      cell-based therapy. Our first aim was to examine the effect of high levels of
      oxidative stress on pMSC functions. pMSCs were exposed to hydrogen peroxide
      (H2O2) and their ability to proliferate and adhere to an endothelial cell
      monolayer was determined. Oxidatively stressed pMSCs maintained their
      proliferation and adhesion potentials. The second aim was to measure the ability
      of pMSCs to prevent oxidative stress-related damage to endothelial cells.
      Endothelial cells were exposed to H2O2, then co-cultured with pMSCs, and the
      effect on endothelial cell adhesion, proliferation and migration was determined.
      pMSCs were able to reverse the damaging effects of oxidative stress on the
      proliferation and migration but not on the adhesion of endothelial cells. These
      data indicate that pMSCs are not only inherently resistant to oxidative stress,
      but also protect endothelial cell functions from oxidative stress-associated
      damage. Therefore, pMSCs could be used as a therapeutic tool in inflammatory
      diseases by reducing the effects of oxidative stress on endothelial cells.

PMID- 28502525
TI  - Editorial.

PMID- 28502526
TI  - Long-term preservation of eri and ailanthus silkworms using frozen gonads.
AB  - Cryopreservation of eri and ailanthus silkworms using frozen gonads was
      investigated. First, we evaluated the freeze tolerance of ovary and testis in the
      eri silkworm, which showed high tolerance. Mating between frozen ovary
      transplanted females and frozen testis-transplanted males produced 163.0 eggs,
      yielding 105.7 larvae per moth. In a second experiment, we tested the use of the
      eri silkworm as a host insect for gonad transplantation from ailanthus silkworm
      donors. A high success ratio for laid and hatched eggs was demonstrated for ovary
      transplantation (97.8 and 51.3 eggs per moth, respectively). For testis
      transplantation, however, the average number of hatched larvae was low (12.0).
      Mating between host eri females and males in which both frozen ovary and testis
      of the ailanthus silkworm had been transplanted produced 6.4 fertilized eggs per
      host moth. Our success in using cross subspecies cryopreservation between these
      wild silkworms could lead to the alternative use of hosts between species in
      other insects.

PMID- 28502527
TI  - Effects of different sucrose concentrations on vitrified porcine preantral
      follicles: Qualitative and quantitative analysis.
AB  - The aim of the present study was to perform a qualitative and quantitative
      analysis of the effect of different sucrose concentrations combined with ethylene
      glycol in the preservation of vitrified porcine preantral follicles. Fragments of
      ovarian cortex were vitrified in cryotubes containing 200 MUl of the
      vitrification solution (30% Ethylene Glycol; 20% Fetal Bovine Serum; 0 M-0.25 M -
      0.75 M or 1 M sucrose) and stored in liquid nitrogen for a week. Histological
      analysis showed that after vitrification the number of normal follicles decreased
      compared to the fresh tissue (control). The percentage of normal primordial
      follicles was sucrose dose dependent. The percentage of normal primary follicles
      was similar in 0 M or 0.25 M sucrose, while higher concentrations (0.75 M and 1
      M) increased significantly the percentage of abnormal follicles (p < 0.05).
      Morphometric analysis showed a statistically significant reduction in the total
      area of primordial follicles with 0.75 M sucrose and a significant increase in
      the cytoplasmic area of primordial follicles with 0 M sucrose (p < 0.05). The
      qualitative and the quantitative analysis appear to be a complementary tool when
      choosing a vitrification protocol. For our cryopreservation system -
      vitrification of ovarian cortex slices in cryotubes-the best vitrification medium
      was TCM 199-Hepes with 30% de ethylene glycol, 20% of Fetal Bovine Serum and 0 or
      0.25 M sucrose. The present study shows that the use of high sucrose
      concentrations in the vitrification solution has a deleterious effect on the
      preservation of porcine preantral follicles contained in ovarian tissue.
      Consequently, its use at 0.75 M or 1 M wouldn't be recommended.

PMID- 28502528
TI  - Neural response to catecholamine depletion in remitted bulimia nervosa: Relation
      to depression and relapse.
AB  - Bulimia nervosa has been associated with a dysregulated catecholamine system.
      Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural
      activity, and on the course of the illness is not clear yet. An instructive
      paradigm for directly investigating the relationship between catecholaminergic
      functioning and bulimia nervosa has involved the behavioral and neural responses
      to experimental catecholamine depletion. The purpose of this study was to examine
      the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its
      relationship to relapse. In a randomized, double-blind and crossover study
      design, catecholamine depletion was achieved by using the oral administration of
      alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22
      healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a
      pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up
      telephone interview, bulimic relapse was assessed. Following AMPT, rBN
      participants revealed an increased vigor reduction and CBF decreases in the
      pallidum and posterior midcingulate cortex (pMCC) relative to HC participants
      showing no CBF changes in these regions. These results indicated that the
      pallidum and the pMCC are the functional neural correlates of the dysregulated
      catecholamine system in bulimia nervosa. Bulimic relapse was associated with
      increased depressive symptoms and CBF reduction in the
      hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced
      increased CBF in this region predicted staying in remission. These findings
      demonstrated the importance of depressive symptoms and the stress system in the
      course of bulimia nervosa.

PMID- 28502530
TI  - The Operating Room of the Future Versus the Future of the Operating Room.
AB  - Technological advancement in the operating room is evolving into a dynamic system
      mirroring that of the aeronautics industry. Through data visualization,
      information is continuously being captured, collected, and stored on a scalable
      informatics platform for rapid, intuitive, iterative learning. The authors
      believe this philosophy (paradigm) will feed into an intelligent informatics
      domain fully accessible to all and geared toward precision, cell-based therapy in
      which tissue can be targeted and interrogated in situ. In the future, the
      operating room will be a venue that facilitates this real-time tissue
      interrogation, which will guide in situ therapeutics to restore the state of
      health.

PMID- 28502532
TI  - Retraction.

PMID- 28502531
TI  - Technological Advances in Sinus and Skull Base Surgery.

PMID- 28502533
TI  - Harnessing Technology at the Edges of Otolaryngology.

PMID- 28502529
TI  - Mechanisms underlying the early risk to develop anxiety and depression: A
      translational approach.
AB  - Anxious temperament (AT) is an early life disposition that markedly increases the
      risk to develop stress related psychopathology such as anxiety and depressive
      disorders. Since anxiety and depression are common, and frequently have their
      onset early in life, a better understanding of the factors related to their
      childhood onset will facilitate the development of new more effective neurally
      informed interventions. A nonhuman primate (NHP) developmental model of childhood
      AT has been established, which has provided an understanding of the neural
      systems and molecular mechanisms mediating the development of AT. Multimodal
      neuroimaging studies reveal altered brain metabolism across prefrontal, limbic
      (e.g. central nucleus of the amygdala (Ce) and anterior hippocampus), and
      brainstem regions, as well as altered functional connectivity involving the Ce.
      Heritability studies demonstrate that individual variation in AT is heritable,
      and genetic correlational analyses demonstrate that metabolism in the posterior
      orbital frontal cortex, the bed nucleus of the stria terminalis, and the
      periaqueductal gray share a genetic substrate with AT. On a molecular level, the
      finding of reduced expression of Ce neuroplasticity genes provides the basis for
      a neurodevelopmental hypothesis focused on the Ce. Viral vector methods for
      altering gene expression in the Ce of young NHPs are currently being used as a
      prelude to conceptualizing novel molecularly targeted early life interventions.

PMID- 28502534
TI  - Disrupted self in Alzheimer's disease: Beyond midline structures: Commentary on
      Wong et al.

PMID- 28502535
TI  - Even "Cementless" Surgeons Use Cement.
AB  - BACKGROUND: Patients presenting with hip arthritis have huge variability in
      anatomy, bone quality, and functional expectation. These can contribute to a
      varying degree of complexity on both the femoral and acetabular sides. Surgeons
      should be aware of all the various options in fixation, bearing surface, and
      surgical technique. METHODS: In this article, based on a presentation given at
      the recent American Association of Hip and Knee Surgeons meeting in Dallas, we
      will discuss why and how cemented fixation can, and indeed should, be considered
      when making decisions regarding how a primary, complex primary, or revision hip
      arthroplasty should be performed. RESULTS: We will review the evidence, surgical
      technique, and indications for cemented fixation in primary and complex primary
      surgery. In addition, we will discuss the potential benefits at revision of
      previous cemented fixation. CONCLUSION: We hope to support the concept that even
      cementless surgeons should also use cement.

PMID- 28502536
TI  - Results of a Modular Revision System in Total Knee Arthroplasty.
AB  - BACKGROUND: Revision total knee arthroplasty (TKA) poses unique challenges
      compared with primary TKA such as bone loss, deformity, and ligament instability.
      Modular component options allow flexibility to deal with these complexities. The
      purpose of this study was to evaluate midterm outcomes for revision TKA using a
      modular revision knee system with complete interchangeability and multiple
      options for augmentation, offset, constraint, and stem extensions. METHODS: A
      query of our practice registry revealed 257 consented patients (274 knees and 278
      TKA) with minimum 2-year follow-up who underwent aseptic revision TKA with a
      modular system (Vanguard Super Stabilized Knee; Zimmer Biomet, Warsaw, IN)
      between 2005 and 2013. Four patients were rerevised to a second Vanguard Super
      Stabilized Knee within the study period. Mean age was 68 years, and mean number
      of previous surgeries was 2 (1-14). RESULTS: At mean follow-up of 6.0 years
      (range, 2-11 years), there have been 25 aseptic revisions involving one or more
      components (9.0%): 15 aseptic loosening with concomitant instability in 2, 8
      others with instability, 1 with hypersensitivity, and 1 revised elsewhere for
      unknown cause. Ten knees were revised for infection. Range of motion improved
      from 100 degrees  preoperatively to 105 degrees  most recently. Knee Society
      clinical scores improved from 45 to 79, and function scores from 46 to 56.
      Radiographic evaluation revealed satisfactory position, fixation, and alignment
      in 97% and abnormal findings in 7 knees: 4 limited to the patella, 1 tibial
      radiolucency, 1 femoral and tibial radiolucency, and 1 tibial subsidence.
      CONCLUSION: The results of this modular TKA revision system at 6 years mean
      follow-up are promising for use in complex scenarios, with a low frequency of
      aseptic rerevision, good knee stability, and substantial improvements in range of
      motion and clinical and functional outcomes.

PMID- 28502539
TI  - Racial differences in functional decline in peripheral artery disease and
      associations with socioeconomic status and education.
AB  - OBJECTIVE: The objective of this study was to determine whether blacks with lower
      extremity peripheral artery disease (PAD) have faster functional decline than
      whites with PAD. METHODS: Participants with ankle-brachial index <0.90 were
      identified from Chicago medical centers and observed longitudinally. Mobility
      impairment and the 6-minute walk were assessed at baseline and every 6 to 12
      months. Mobility loss was defined as becoming unable to walk up and down a flight
      of stairs or to walk 1/4 mile without assistance. RESULTS: Of 1162 PAD
      participants, 305 (26%) were black. Median follow-up was 46.0 months. Among 711
      PAD participants who walked 6 minutes continuously at baseline, black
      participants were more likely to become unable to walk 6 minutes continuously
      during follow-up (64/171 [37.4%] vs 156/540 [28.9%]; log-rank, P = .006). Black
      race was associated with becoming unable to walk 6 minutes continuously,
      adjusting for age, sex, ankle-brachial index, comorbidities, and other
      confounders (hazard ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022).
      This association was attenuated after adjustment for income and education (P =
      .229). Among 844 participants without baseline mobility impairment, black
      participants had a higher rate of mobility loss (64/209 [30.6%] vs 164/635
      [25.8%]; log-rank, P = .009). Black race was associated with increased mobility
      loss, adjusting for potential confounders (hazard ratio, 1.42; 95% confidence
      interval, 1.04-1.94; P = .028). This association was attenuated after additional
      adjustment for income and education (P = .392) and physical activity (P = .113).
      There were no racial differences in average annual declines in 6-minute walk,
      usual-paced 4-meter walking velocity, or fast-paced 4-meter walking velocity.
      CONCLUSIONS: Black PAD patients have higher rates of mobility loss and becoming
      unable to walk for 6 minutes continuously. These differences appear related to
      racial differences in socioeconomic status and physical activity.

PMID- 28502540
TI  - Trends and outcomes in endovascular and open surgical treatment of visceral
      aneurysms.
AB  - OBJECTIVE: Visceral artery aneurysms (VAAs) are rare but often repaired because
      of dire consequences of rupture. This is a population-based evaluation of
      chronologic trends in management, risk factors, and outcomes of endovascular and
      open therapy. METHODS: The 2003 to 2013 Agency for Healthcare Research and
      Quality (AHRQ) National Inpatient Sample (NIS) database was reviewed. Cases with
      primary diagnosis of VAA and undergoing endovascular or open repair were
      identified. Patients with renal artery or abdominal or thoracoabdominal aortic
      disease were excluded. Case numbers of respective techniques were charted over
      time. Baseline characteristics and in-hospital outcomes were compared for
      endovascular and open groups using chi2 test, Fisher exact test, or t-test.
      Predictors of mortality and complications were evaluated with multivariate
      logistic regression. RESULTS: There were 9260 interventions for VAAs from 2003 to
      2013, including 5166 endovascular and 4094 open. Endovascular repairs increased
      from 5.3 to 24.7 per 10 million U.S. population (P < .001), surpassing open
      repairs in 2008, which decreased from 14.3 to 9.2 per 10 million (P < .001).
      Endovascular patients were more likely to have been treated at urban teaching
      hospitals (77.1% vs 61.8%; P < .0001); to have higher proportions of renal
      failure (7.6% vs 4.9%; P = .02), liver disease (11.3% vs 6.6%; P < .001), alcohol
      abuse (13.1% vs 3.6%; P < .001), chronic blood loss anemia (4.5% vs 1.6%; P <
      .001), metastatic cancer (2.7% vs 0.8%; P = .003), solid tumor without metastases
      (3.6% vs 2.0%; P < .037), and weight loss (9.8% vs 5.2%; P < .001); and less
      likely to have had elective admission (28.9% vs 59.8%; P < .0001). In-hospital
      mortality (4.1% vs 4.5%; P = .618) and overall complication rates (37.8% vs
      38.8%; P = .688) were similar between groups; however, pulmonary complications
      were decreased for endovascular patients (10.6% vs 19.7%; P < .001). Endovascular
      patients had shorter hospital stays (6.5 vs 8.7 days; P < .001). Multivariate
      adjustment for mortality predictors, including coagulopathy (odds ratio [OR],
      4.34; confidence interval [CI], 2.56-7.35; P < .001), liver disease (OR, 2.25;
      CI, 1.25-4.07; P = .01), fluid and electrolyte disorders (OR, 2.84; CI, 1.73
      4.66; P < .001), and solid tumor without metastases (OR, 2.81; CI, 1.10-7.18; P =
      .03), showed that open treatment was associated with increased mortality (OR,
      1.70; CI, 1.03-2.81; P = .04). Analysis of overall complications revealed that
      open treatment was again associated with increased complications (OR, 1.78; CI,
      1.43-2.21; P < .001). CONCLUSIONS: Endovascular VAA repairs are increasing.
      Despite patients' having worse comorbidities and more nonelective admissions,
      endovascular therapy appears to be associated with decreased mortality and
      complications and shorter hospital stays.

PMID- 28502541
TI  - Prolonged stance phase during walking in intermittent claudication.
AB  - BACKGROUND: Patients with intermittent claudication (IC) tend to walk slower and
      consume approximately 40% more oxygen during walking compared with healthy
      individuals. An unfavorable locomotion pattern has been suggested to explain this
      metabolic inefficiency. However, detailed knowledge of gait parameters in IC is
      lacking. METHODS: In a cross-sectional study, the gait pattern of newly diagnosed
      IC patients was compared with that of healthy controls. Spatiotemporal gait
      parameters such as step length and duration of stance phase were obtained by a
      photoelectric technique (OptoGait; Microgate, Bolzano, Italy). This system was
      previously found to have favorable concurrent validity and test-retest
      reliability characteristics. Parameters were determined during pain-free and
      painful treadmill walking at a comfortable self-determined walking pace. Each
      parameter was averaged on the basis of 80 steps. RESULTS: A total of 28 patients
      and 28 controls were examined. IC patients walked 1.2 km/h (-27%) slower than
      controls (P < .001), coinciding with a significantly shorter step length (-20%)
      and lower cadence (-11%). IC patients demonstrated a longer stance and double
      support phase, even before the onset of ischemic pain. Differences were also
      observed in segments of the stance phase, as a 14% shorter propulsion (P < .001)
      and 17% longer flat foot phase (P < .001) during painful walking were found. In
      considering the absolute duration of these stance phase segments, differences
      were found only for the flat foot time (Delta0.10 second; P < .001). CONCLUSIONS:
      Patients with IC demonstrate an altered gait pattern compared with healthy
      controls. The most prominent differences were a prolonged relative and absolute
      duration of the flat foot position during the stance phase. This adaptation may
      be intuitive as an augmented arterial blood flow into skeletal muscles is allowed
      during a prolonged relaxation phase. Therefore, not only the lack of propulsion
      but also a gain of relaxation may explain these gait alterations.

PMID- 28502542
TI  - Contemporary evaluation of mortality and stroke risk after thoracic endovascular
      aortic repair.
AB  - OBJECTIVE: During the past decade, thoracic endovascular aortic repair (TEVAR)
      has increased as a treatment option for a variety of aortic pathologic processes.
      Despite this rise in the use of thoracic stent grafts, real-world outcomes from a
      robust, adjudicated, contemporary data set have yet to be reported. Previous
      studies have shown periprocedural mortality rates between 1.5% and 9.5% and
      procedure-related stroke rates of 2.3% to 8.2%. With advances in device
      engineering and increased experience of physicians, we hypothesized that the
      rates of these complications would be reduced in a more recent sample set. The
      purpose of this study was to determine current rates of mortality and stroke
      after TEVAR, to identify risk factors that contribute to 30-day mortality, and to
      develop a simple scoring system that allows risk stratification of patients
      undergoing TEVAR. METHODS: We examined the 30-day mortality rate after TEVAR
      using the 2013 to 2014 American College of Surgeons National Surgical Quality
      Improvement Program database. Patients undergoing TEVAR for all aortic disease
      were identified using procedure codes. Bivariate analyses were performed to
      evaluate the association of preoperative, intraoperative, and postoperative
      variables with 30-day mortality, followed by multivariable logistic analysis
      using preoperative variables only, with P < .10 as the criterion for model entry.
      The predictive logistic model was internally validated by cross-validation.
      Variables included in the multivariable model were used to develop a risk score.
      RESULTS: There were 826 patients included. The 30-day mortality and stroke rates
      were 7.63% (n = 63) and 4.5% (n = 37), respectively. In regression analysis,
      mortality was independently associated with age >=80 years (odds ratio [OR],
      2.32; 95% confidence interval [CI], 1.25-4.31), emergency case (OR, 2.61; 95% CI,
      1.39-4.90), American Society of Anesthesiologists classification >3 (OR, 2.89;
      95% CI, 1.34-6.24), transfusion >4 units in the 72 hours before surgery (OR,
      2.86; 95% CI, 1.30-6.28), preoperative creatinine concentration >=1.8 mg/dL (OR,
      2.07; 95% CI, 1.05-4.08), and preoperative white blood cell count >=12 * 109/L
      (OR, 2.65; 95% CI, 1.41-4.96). Incorporating these factors, a 6-point risk score
      was generated and demonstrated high predictability for overall 30-day mortality.
      CONCLUSIONS: Recent data from a national, retrospective data set demonstrate that
      high perioperative mortality and stroke rates have persisted during the last
      decade. The risk score derived from this data set is simple and convenient and
      serves as a prognostic tool in the preoperative risk stratification of patients
      being evaluated for TEVAR.

PMID- 28502543
TI  - The association of Carotid Revascularization Endarterectomy versus Stent Trial
      (CREST) and Centers for Medicare and Medicaid Services Carotid Guideline
      Publication on utilization and outcomes of carotid stenting among "high-risk"
      patients.
AB  - OBJECTIVE: Since the 2004 approval by the United States Food and Drug
      Administration of carotid artery stenting (CAS), there have been two seminal
      publications about CAS reimbursement (Centers for Medicare and Medicaid Services
      guidelines; 2008) and clinical outcomes (Carotid Revascularization Endarterectomy
      versus Stent Trial [CREST]; 2010). We explored the association between these
      publications and national trends in CAS use among high-risk symptomatic patients.
      METHODS: The most recent congruent data sets of the Nationwide Inpatient Sample
      (NIS) were queried for patients undergoing carotid revascularization. The sample
      was limited to include only patients who were defined as "high-risk" if they had
      a Charlson Comorbidity Score of >=3.0. Subgroup analyses were performed of high
      risk patients with symptomatic carotid stenosis. Utilization proportions of CAS
      were calculated quarterly from 2005 to 2011 for NIS. Three time intervals related
      to Centers for Medicare and Medicaid Services guidelines and CREST publication
      were selected: 2005 to 2008, 2008 to 2010, and after 2010. Logistic regression
      with piecewise linear trend for time was used to estimate different trends in CAS
      use for the overall high-risk sample and for neurologically asymptomatic and
      symptomatic cases. Multivariate logistic regression was used to compare odds of
      postoperative mortality and stroke between these two procedures at different time
      intervals independent of confounding variables. RESULTS: During the study period,
      20,079 carotid endarterectomies (CEAs) and 3447 CAS procedures were performed in
      high-risk patients in the NIS database. CAS utilization constituted 20.5% of
      carotid revascularization procedures among high-risk symptomatic patients, with a
      significant increase from 18.6% to 24.4% during the study period (P < .001).
      There was an initial increase during 2005 to 2008 in the rate of CAS compared
      with CEA, CAS utilization significantly decreased during 2008 to 2010 by a 3.3%
      decline in the odds ratio (OR) of CAS per quarter (OR, 0.967; 95% confidence
      interval [CI], 0.943-0.993; P = .002), and after CREST (after 2010), CAS
      utilization continued to increase significantly from the prepublication to the
      postpublication time interval. The odds of in-hospital mortality (OR, 2.56; 95%
      CI, 1.17-5.62; P = .019) and postoperative in-hospital stroke (OR, 1.53; 95% CI,
      1.09-3.68; P = .024) were independently and significantly higher for CAS patients
      in the overall sample. CONCLUSIONS: The use of CAS for carotid revascularization
      in a high-risk cohort of patients has significantly increased from 2005 to 2011.
      Compared with CEA, CAS independently increased the odds of perioperative in
      hospital stroke in all high-risk patients and of in-hospital mortality in
      symptomatic high-risk patients.

PMID- 28502545
TI  - Durability of iliac artery preservation associated with endovascular repair of
      infrarenal aortoiliac aneurysms.
AB  - OBJECTIVE: This study evaluated and compared the long-term clinical outcomes of
      endovascular repair of infrarenal aortoiliac aneurysms (EVAR) vs EVAR with
      preservation of antegrade internal iliac artery (IIA) perfusion using iliac
      branched devices (EVAR-IBDs). METHODS: From October 1998 to August 2015, patients
      with infrarenal aortoiliac aneurysmal (AIA) disease at high risk for conventional
      open surgery were enrolled in a prospective physician-sponsored investigational
      device exemption trial. Clinical data of 75 patients treated with EVAR-IBD and
      255 with standard EVAR were analyzed. Technical success, perioperative outcomes,
      mortality, device patency, endoleak rates, and reinterventions during a follow-up
      of 10 years were analyzed. RESULTS: There were 87 IBDs deployed in 75 patients.
      Technical success rate was 97%. Mortality at 30 days was 1.3%. Freedom from
      aneurysm-related mortality at 3, 5, and 10 years was 99%. Freedom from a type I
      or III endoleak at 3, 5, and 10 years was 99%. Freedom from secondary
      reinterventions at 3, 5, and 10 years was 86%, 81%, and 81%, respectively.
      Primary patency of the IBDs at 3, 5, and 10 years was 94%, 94%, and 77%,
      respectively. Twenty-four percent of patients underwent EVAR for concomitant AIA
      disease (EVAR-AIA), and 78% were managed by staged IIA embolization before EVAR.
      No statistically significant difference in freedom from aneurysm-related
      mortality, limb occlusions, or endoleak rates was identified in patients with
      EVAR-AIA vs EVAR-IBD (P > .05). There were significantly more secondary
      reinterventions in the EVAR-AIA group compared with the EVAR-IBD group (hazard
      ratio, 0.476, 95% confidence interval, 0.226-1.001; P = .045). CONCLUSIONS: EVAR
      of infrarenal AIAs with preservation of antegrade flow to the IIA using IBDs is
      feasible with long-term sustained durability. Serious considerations should be
      given to the use of IBDs in patients with infrarenal AIAs meeting appropriate
      anatomic criteria.

PMID- 28502544
TI  - First experience with the double chimney technique in the treatment of aortic
      arch diseases.
AB  - OBJECTIVE: The objective of this study was to summarize our initial experience
      using the double chimney technique to treat aortic arch diseases. METHODS: From
      December 2009 to October 2016, 23 patients with aortic arch diseases, including
      20 acute aortic dissections, 2 aortic arch aneurysms, and 1 type I endoleak after
      thoracic endovascular aortic repair (TEVAR), were treated using a double chimney
      technique. An emergent operation was performed in only one patient with an acute
      aortic dissection for severe left lower extremity ischemia. All patients were
      observed after TEVAR with computed tomography scans at 2 weeks, at 3 and 6
      months, and annually thereafter. RESULTS: In all patients, aortic arch lesions
      were covered, and supra-aortic branches were patent without morbidity. In 22
      patients, the innominate artery (IA) and left common carotid artery were
      reconstructed with the proximal landing zone in zone 0; in 1 patient, the left
      common carotid artery and left subclavian artery were reconstructed. During the
      procedure, there were three (13.0%) type I endoleaks. Chimney stent graft
      migration occurred in one (4.3%) patient perioperatively; compression of a
      chimney stent graft occurred in one (4.3%) patient 4 days after TEVAR. There were
      no type II endoleaks or perioperative mortality. Median follow-up was 28.0 +/-
      19.8 (range, 3-84) months, with no TEVAR-related deaths. Partial compression of
      the chimney stent graft in the IA occurred at 3 months after TEVAR in one (4.3%)
      patient; three patients had persistent but asymptomatic type I endoleaks.
      CONCLUSIONS: TEVAR using a double chimney technique to reconstruct the supra
      aortic branches provides a safe and minimally invasive alternative procedure
      associated with low postoperative mortality. The main perioperative complications
      include type I endoleak and compression of the chimney stent grafts in the IA.
      More experience with long-term results is needed to evaluate the effectiveness
      and durability of this advanced endovascular procedure.

PMID- 28502546
TI  - Cryopreserved saphenous vein as a last-ditch conduit for limb salvage.
AB  - OBJECTIVE: In patients lacking autogenous vein suitable for infrainguinal bypass,
      cryopreserved saphenous vein (CSV) allograft (CryoLife, Inc, Kennesaw, Ga) may be
      an acceptable alternative. The purpose of this study was to examine outcomes of
      CSV conduit for infrainguinal revascularization. METHODS: Between February 2008
      and August 2015, 70 patients underwent infrainguinal bypass grafts in 73 limbs
      using CSV. All patients lacked suitable arm or leg vein. Demographic data and
      patient outcomes were retrospectively collected using electronic medical records.
      RESULTS: The mean age of our cohort was 70 +/- 14 years, and 36 (51%) were male;
      47 (67%) were white, 39 (56%) had coronary artery disease, 27 (39%) had diabetes,
      56 (80%) had hypertension, and 50 (71%) were former or current smokers. Median
      follow-up was 304 days (interquartile range, 130-991 days). Indications for the
      index operation included rest pain (27%), tissue loss (55%), and prosthetic graft
      infection (18%); 62 of 73 (85%) bypasses were performed for critical limb
      ischemia, and 45 of 73 (62%) were redo operations. Distal targets included
      superficial femoral artery or popliteal (38%), tibial (55%), and pedal (7%). All
      grafts had a minimum diameter of 3 mm. At 30 days, 55 of 64 grafts (86%) were
      patent; 9 were lost to early follow-up. The only significant risk factors
      associated with 30-day failure were ABO mismatch (43% vs 10%; P = .05) and donor
      blood type B or AB (40% vs 9%; P = .03). Estimated overall 1-year primary patency
      was 35%. In a multivariate analysis, nonblack race (P = .05), donor B or AB blood
      type (P = .01), and bypass to a tibial or pedal target (P = .05) were
      independently associated with loss of primary patency. There were 20 (27%) major
      amputations, and all grafts in these limbs had occluded at the time of
      amputation. Of the 33 limbs with ischemic tissue loss that had long-term follow
      up, 17 of 33 (52%) went on to graft occlusion, 10 of 33 (30%) had a major
      amputation, and 24 of 33 (73%) had complete healing of the index wound.
      CONCLUSIONS: In the setting of a multidisciplinary team with aggressive wound
      care, CSV may be a reasonable choice for infrainguinal revascularization in
      patients with ischemic tissue loss who lack autogenous conduit. However, poor
      midterm to long-term patency suggests that optimal selection of patients is
      needed to derive meaningful clinical benefit.

PMID- 28502547
TI  - Carotid artery stenting is associated with a higher incidence of major adverse
      clinical events than carotid endarterectomy in female patients.
AB  - BACKGROUND: The optimal approach to carotid revascularization in female patients
      with carotid artery stenosis is widely debated. Information available is largely
      derived from clinical trials that include only highly selected patients. The goal
      of this study was to compare the early clinical outcomes in women who undergo
      carotid artery stenting (CAS) vs carotid endarterectomy (CEA). METHODS: Female
      patients undergoing CAS or CEA between January 1, 2012 and December 31, 2015, and
      who were included in the Procedure Targeted American College of Surgeons National
      Surgical Quality Improvement Program were assessed for their incidence of early
      postoperative complications. The primary outcome measure was 30-day incidence of
      a major adverse clinical event (MACE; defined as death, stroke, transient
      ischemic attack, or myocardial infarction/arrhythmia). Univariable analyses were
      used to compare results between female patients undergoing CEA and those
      undergoing CAS. Propensity score matching techniques were used to create a cohort
      of 125 CAS and CEA patients who were well matched for all known patient-, disease
      , and procedure-related factors. Analysis of comparative outcomes between the
      propensity-matched groups was then performed. RESULTS: The overall study
      population consisted of 5620 female CEA patients and 131 female CAS patients. Of
      these patients, 290 (5.2%) from the CEA group and 16 (12.2%) from the CAS group
      sustained a MACE in the first 30 days after their procedures. Within the
      propensity-matched cohort, the 30-day incidence of postoperative MACE in the CAS
      group of this cohort was 11.2% (14 patients) compared with 4.0% (5 patients; odds
      ratio, 1.01 [95% confidence interval, 1.01-7.77]; P = .04) in the CEA group.
      CONCLUSIONS: Our analysis of a "real-world" clinical registry suggests that CAS
      may be inferior to CEA in female patients who require carotid artery
      revascularization.

PMID- 28502548
TI  - Lifelong limb preservation: A patient-centered description of lower extremity
      arterial reconstruction outcomes.
AB  - BACKGROUND: Life expectancy is short for patients with critical limb ischemia
      (CLI), many of whom may fear amputation more than death. In light of the reduced
      life expectancy of these patients, the traditional 5-year freedom from amputation
      (FFA) statistic may not accurately address their concern. We developed a more
      relevant patient-centered calculation of major amputation risk during a patient's
      remaining lifetime to better answer the question, Will I ever lose my leg?
      METHODS: We identified all limbs undergoing first-time intervention for CLI in a
      large institutional database from 2005 to 2013. We calculated the traditional
      metrics of amputation-free survival (AFS, for which failure is death or
      amputation) and FFA (for which failure is amputation but deaths are censored and
      removed from further analysis). In addition, we propose a new term, lifelong limb
      preservation (LLP). LLP defines amputation as failure, but deaths are not
      censored and therefore reflect that LLP has been achieved. All deaths before 30
      days were considered a failure in all three metrics, reflecting the risk of
      surgery. RESULTS: There were 1006 limbs identified as having first-time
      intervention for CLI (22% rest pain, 45% ulcer, 27% gangrene; 46% treated by
      angioplasty with or without stenting, 54% bypass). Using life-table analysis, 7
      year AFS was 14% (561 events), FFA was 78% (123 events), and LLP was 86% (123
      events). LLP was similar between patients undergoing angioplasty with or without
      stenting and bypass (7-year rates, 86% and 85%, respectively). For patients
      undergoing intervention for rest pain, 7-year rates were 14% for AFS, 84% for
      FFA, and 92% for LLP. For those undergoing treatment for ulcer, 7-year rates were
      14% for AFS, 77% for FFA, and 86% for LLP. Finally, in those with gangrene, rates
      were 10% for AFS, 67% for FFA, and 79% for LLP. Using LLP, patients presenting
      with an ulcer can be told that although we cannot guarantee how long they will
      live, with revascularization there is approximately an 86% chance they will not
      lose the leg. CONCLUSIONS: These results show that the durability of our limb
      preservation efforts often exceeds the life expectancy of our patients. Using LLP
      as an outcomes assessment provides a more accurate and patient-centered answer to
      the question, If I have this procedure, will I ever lose my leg?

PMID- 28502549
TI  - Reimbursement in hospital-based vascular surgery: Physician and practice
      perspective.
AB  - OBJECTIVE: The purpose of this study was to determine change in value of a
      vascular surgery division to the health care system during 6 years at a hospital
      based academic practice and to compare physician vs hospital revenue earned
      during this period. METHODS: Total revenue generated by the vascular surgery
      service line at an academic medical center from 2010 through 2015 was evaluated.
      Total revenue was measured as the sum of physician (professional) and hospital
      (technical) net revenue for all vascular-related patient care. Adjustments were
      made for work performed, case complexity, and inflation. To reflect the effect of
      these variables, net revenue was indexed to work relative value units (wRVUs),
      case mix index, and consumer price index, which adjusted for work, case
      complexity, and inflation, respectively. Differences in physician and hospital
      net revenue were compared over time. RESULTS: Physician work, measured in RVUs
      per year, increased by 4%; case complexity, assessed with case mix index,
      increased by 10% for the 6-year measurement period. Despite stability in payer
      mix at 64% to 69% Medicare, both physician and hospital vascular-related
      revenue/wRVU decreased during this period. Unadjusted professional revenue/wRVU
      declined by 14.1% (P = .09); when considering case complexity, physician
      revenue/wRVU declined by 20.6% (P = .09). Taking into account both case
      complexity and inflation, physician revenue declined by 27.0% (P = .04).
      Comparatively, hospital revenue for vascular surgery services decreased by 13.8%
      (P = .07) when adjusting for unit work, complexity, and inflation. CONCLUSIONS:
      At medical centers where vascular surgeons are hospital based, vascular care
      reimbursement decreased substantially from 2010 to 2015 when case complexity and
      inflation were considered. Physician reimbursement (professional fees) decreased
      at a significantly greater rate than hospital reimbursement for vascular care.
      This trend has significant implications for salaried vascular surgeons in
      hospital-based settings, where the majority of revenue generated by vascular
      surgery care is the technical component received by the facility. Appropriate
      care for patients with vascular disease is increasingly resource intensive, and
      as a corollary, reimbursement levels must reflect this situation if high-quality
      care is to be maintained.

PMID- 28502550
TI  - Lower extremity computed tomography angiography can help predict technical
      success of endovascular revascularization in the superficial femoral and
      popliteal artery.
AB  - OBJECTIVE: Preprocedural computed tomography angiography (CTA) assists in
      evaluating vascular morphology and disease distribution and in treatment planning
      for patients with lower extremity peripheral artery disease (PAD). The aim of the
      study was to determine the predictive value of radiographic findings on CTA and
      technical success of endovascular revascularization of occlusions in the
      superficial femoral artery-popliteal (SFA-pop) region. METHODS: Medical records
      and available imaging studies were reviewed for patients undergoing endovascular
      intervention for PAD between January 2013 and December 2015 at a single academic
      institution. Radiologists reviewed preoperative CTA scans of patients with
      occlusions in the SFA-pop region. Radiographic criteria previously used to
      evaluate chronic occlusions in the coronary arteries were used. Technical
      success, defined as restoration of inline flow through the SFA-pop region with
      <30% stenosis at the end of the procedure, and intraoperative details were
      evaluated. RESULTS: From 2013 to 2015, there were 407 patients who underwent 540
      endovascular procedures for PAD. Preprocedural CTA scans were performed in 217
      patients (53.3%), and 84 occlusions in the SFA-pop region were diagnosed. Ten
      occlusions were excluded as no endovascular attempt to cross the lesion was made
      because of extensive disease or concomitant iliac intervention. Of the remaining
      74 occlusions in the SFA-pop region, 59 were successfully treated (80%) and 15
      were unsuccessfully crossed (20%). The indications for revascularization were
      claudication in 57% of patients and critical limb ischemia in the remaining
      patients. TransAtlantic Inter-Society Consensus A, B, and C occlusions were
      treated with 87% success, whereas D occlusions were treated with 68% success (P =
      .047). There were nine occlusions with 100% vessel calcification that was
      associated with technical failure (P = .014). Longer lengths of occlusion were
      also associated with technical failure (P = .042). Multiple occlusions (P = .55),
      negative remodeling (P = .69), vessel runoff (P = .56), and percentage of vessel
      calcification (P = .059) were not associated with failure. On multivariable
      analysis, 100% calcification remained the only significant predictor of technical
      failure (odds ratio, 9.0; 95% confidence interval, 1.8-45.8; P = .008).
      CONCLUSIONS: Analysis of preoperative CTA shows 100% calcification as the best
      predictor of technical failure of endovascular revascularization of occlusions in
      the SFA-pop region. Further studies are needed to determine the cost
      effectiveness of obtaining preoperative CTA for lower extremity PAD.

PMID- 28502551
TI  - Variation in hospital costs and reimbursement for endovascular aneurysm repair: A
      Vascular Quality Initiative pilot project.
AB  - OBJECTIVE: Comparing costs between centers is difficult because of the
      heterogeneity of vascular procedures contained in broad diagnosis-related group
      (DRG) billing categories. The purpose of this pilot project was to develop a
      mechanism to merge Vascular Quality Initiative (VQI) clinical data with hospital
      billing data to allow more accurate cost and reimbursement comparison for
      endovascular aneurysm repair (EVAR) procedures across centers. METHODS: Eighteen
      VQI centers volunteered to submit UB04 billing data for 782 primary, elective
      infrarenal EVAR procedures performed by 108 surgeons in 2014. Procedures were
      categorized as standard or complex (with femoral-femoral bypass or additional
      arterial treatment) and without or with complications (arterial injury or
      embolectomy; bowel or leg ischemia; wound infection; reoperation; or cardiac,
      pulmonary, or renal complications), yielding four clinical groups for comparison.
      MedAssets, Inc, using cost to charge ratios, calculated total hospital costs and
      cost categories. Cost variation analyzed across centers was compared with DRG 237
      (with major complication or comorbidity) and 238 (without major complication or
      comorbidity) coding. A multivariable model to predict DRG 237 coding was
      developed using VQI clinical data. RESULTS: Of the 782 EVAR procedures, 56% were
      standard and 15% had complications, with wide variation between centers. Mean
      total costs ranged from $31,100 for standard EVAR without complications to
      $47,400 for complex EVAR with complications and varied twofold to threefold among
      centers. Implant costs for standard EVAR without complications varied from $8100
      to $28,200 across centers. Average Medicare reimbursement was less than total
      cost except for standard EVAR without complications. Only 9% of all procedures
      with complications in the VQI were reported in the higher reimbursed DRG 237
      category (center range, 0%-21%). There was significant variation in hospitals'
      coding of DRG 237 compared with their expected rates. VQI clinical data
      accurately predict current DRG coding (C statistic, 0.87). CONCLUSIONS: VQI data
      allow a more precise EVAR cost comparison by identifying comparable clinical
      groups compared with DRG-based calculations. Total costs exceeded Medicare
      reimbursement, especially for patients with complications, although this varied
      by center. Implant costs also varied more than expected between centers for
      comparable cases. Incorporation of VQI data elements documenting EVAR case
      complexity into billing data may allow centers to better align respective DRG
      reimbursement to total costs.

PMID- 28502552
TI  - Bifurcated-bifurcated aneurysm repair is a novel technique to repair infrarenal
      aortic aneurysms in the setting of iliac aneurysms.
AB  - BACKGROUND: Up to 40% of abdominal aortic aneurysms (AAAs) have coexistent iliac
      artery aneurysms (IAAs). In the past, successful endovascular repair required
      internal iliac artery (IIA) embolization, which can lead to pelvic or buttock
      ischemia. This study describes a technique that uses a readily available solution
      with a minimally altered off-the-shelf bifurcated graft in the IAA to maintain
      IIA perfusion. METHODS: From August 2009 to May 2015, 14 patients with AAAs and
      coexisting IAAs underwent repair with a bifurcated-bifurcated approach. A 22-mm
      or 24-mm bifurcated main body device was used in the IAA with extension of the
      "contralateral" limb into the IIA. Intraoperative details including operative
      time, fluoroscopy time, and contrast agent use were recorded. Outcome measures
      assessed were operative technical success and a composite outcome measure of IIA
      patency, freedom from reintervention, and clinically significant endoleak at 1
      year. RESULTS: Fourteen patients underwent bifurcated-bifurcated repair during
      the study period. Technical success was achieved in 93% of patients, with
      successful treatment of the AAA and IAA and preservation of flow to at least one
      IIA. The procedure was performed with a completely percutaneous bilateral femoral
      approach in 92% of patients. Three patients had a type II endoleak on initial
      follow-up imaging, but none were clinically significant. There were no cases of
      bowel ischemia or erectile dysfunction. One patient had buttock claudication
      ipsilateral to IIA coil embolization (contralateral to bifurcated iliac repair
      and preserved IIA) that resolved by 6-month follow-up. Two patients required
      reinterventions. One patient presented to his first follow-up visit on
      postoperative day 25 with thrombosis of the right external iliac limb ipsilateral
      to the bifurcated iliac repair, which was successfully treated with thrombectomy
      and stenting of the limb. This same patient presented at 83 months with growth of
      the preserved IIA to 3.9 cm and underwent coil embolization of the aneurysm.
      Another patient presented for surveillance 44 months after his original repair
      with component separation of the mating stent and the iliac bifurcated stent
      grafts. This was treated with a limb extension and endoanchors to fuse the
      endografts. Of the 13 patients who underwent bifurcated-bifurcated repair, 100%
      of the preserved IIAs remained patent at last follow-up. The composite outcome
      measure of IIA patency and freedom from reintervention and clinically significant
      endoleak at 1 year was 92% (n = 12/13). CONCLUSIONS: In this small retrospective
      review, bifurcated-bifurcated aneurysm repair of aortoiliac aneurysms with
      preservation of perfusion to the IIA is technically feasible and safe with good
      short-term and midterm results in male patients.

PMID- 28502553
TI  - A shortened protocol for assessing cognitive bias in rats.
AB  - BACKGROUND: Reliable measurement of affective state in animals is a significant
      goal of animal welfare. Such measurements would also improve the validity of pre
      clinical mental health research which relies on animal models. However, at
      present, affective states in animals are inaccessible to direct measurement. In
      humans, changes in cognitive processing can give reliable indications of
      emotional state. Therefore, similar techniques are increasingly being used to
      gain proxy measures of affective states in animals. In particular, the 'cognitive
      bias' assay has gained popularity in recent years. Major disadvantages of this
      technique include length of time taken for animals to acquire the task (typically
      several weeks), negative experiences associated with task training, and issues of
      motivation. NEW METHOD: Here we present a shortened cognitive bias protocol using
      only positive reinforcers which must actively be responded to. RESULTS: The
      protocol took an average of 4days to complete, and produced similar results to
      previous, longer methods (minimum 30days). Specifically, rats housed in standard
      laboratory conditions demonstrated negative cognitive biases when presented with
      ambiguous stimuli, and took longer to make a decision when faced with an
      ambiguous stimulus. COMPARISON WITH EXISTING METHODS: Compared to previous
      methods, this protocol is significantly shorter (average 4days vs. minimum
      30days), utilises only positive reinforcers to avoid inducing negative affective
      states, and requires active responses to all cues, avoiding potential confounds
      of motivational state. CONCLUSIONS: We have successfully developed a shortened
      cognitive bias protocol, suitable for use with laboratory rats.

PMID- 28502554
TI  - The 9 to 5 Rodent - Time for Change? Scientific and animal welfare implications
      of circadian and light effects on laboratory mice and rats.
AB  - Rodents, particularly rats and mice, are the most commonly used laboratory
      animals and are extensively used in neuroscience research, including as
      translational models for human disorders. It is common practice to carry out
      scientific procedures on rats and mice during the daytime, which is the inactive
      period for these nocturnal species. However, there is increasing evidence for
      circadian and light-induced effects on rodent physiology and behaviour which may
      affect the validity of results obtained from mice and rats in neuroscience
      studies. For example, testing animals during their inactive periods may produce
      abnormal results due to cognitive deficits, lack of motivation to perform the
      task or stress from being disturbed during the resting period. In addition,
      conducting procedures during an animal's resting period may also pose an animal
      welfare issue, as procedures may be experienced as more stressful than if these
      were done during the active phase. In this paper we set out the need to consider
      the impact of time of day and lighting conditions, when scientific procedures or
      routine husbandry are performed, on both the welfare of mice and rats used in
      neuroscience research and on data quality. Wherever possible, husbandry and
      experimental procedures should be conducted at times of day when the animals
      would be active, and under naturalistic lighting conditions, to minimise stress
      and maximise data quality and translatability.

PMID- 28502555
TI  - Nivolumab in Second-Line Treatment for Advanced Non-Small-Cell Lung Cancer With
      Squamous-Cell Histology: A Perspective Based on Pharmacologic Costs.

PMID- 28502556
TI  - Morbidity and mortality conference is not sufficient for surgical quality
      control: Processes and outcomes of a successful attending Physician Peer Review
      committee.
AB  - BACKGROUND: Physician Peer Review (PPR) is required by The Joint Commission to
      assure examination of individual and group outcomes. Although surgeons may
      utilize Morbidity and Mortality (M&M) conference, applying these data to
      determine Focused Professional Practice Evaluations involves outcomes review. A
      PPR Committee of senior surgeons was created. This report describes one
      institution's surgical PPR process and results. METHOD: A two-year (2014-2015)
      retrospective review of significant non-trauma complications and unanticipated
      deaths evaluated by PPR was performed. A faculty questionnaire evaluated
      perceptions of quality outcomes reporting. RESULTS: Of 395 reviewed cases, almost
      half (48.9%) demonstrated no care improvement opportunities, 48.6% revealed
      possible improvements, 2% were deviations from standard of care, and 0.5%
      represented unacceptable care. Although most surgeons (94%) wanted to know their
      complication rates, only 41% reported maintaining an outcomes database.
      CONCLUSIONS: As a complement to M&M, PPR is a valuable tool in the evaluation of
      individual surgical quality and can be the basis for further quality improvement
      opportunities. This process has been largely successful; only a small number of
      significant concerns were discovered.

PMID- 28502557
TI  - Antecedents and early correlates of high and low concentrations of angiogenic
      proteins in extremely preterm newborns.
AB  - BACKGROUND: To identify the antecedents and very early correlates of low
      concentrations of angiogenic proteins in the blood of extremely preterm newborns
      during the first postnatal month. METHODS: Using multiplex immunoassays we
      measured the concentrations of vascular endothelial growth factor A (VEGF), VEGF
      receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), placenta growth factor (PIGF),
      and angiopoietins 1 and 2 (Ang-1, Ang-2), as well as 21 other proteins in blood
      spots collected on postnatal days 1 (N=1062), 7 (N=1087), 14 (N=989), 21 (N=940)
      and 28 (N=880) from infants born before the 28th week of gestation. We then
      sought the protein-concentration correlates of concentrations in the top and
      bottom quartile for gestational age and day the specimen was collected. RESULTS:
      Children who were delivered for medical indications and those who were severely
      growth restricted were more likely than others to have low day-1 blood
      concentrations of VEGF, VEGF-R2, Ang-1, and PIGF. Systemic inflammation
      accompanied top quartile concentrations of every one of the 6 angiogenic
      proteins. CONCLUSIONS: Low day-1 concentrations of most angiogenic proteins are
      associated with disorders linked to placenta insufficiency/dysfunction. High
      concentrations, on the other hand, are associated with systemic inflammation
      throughout the first postnatal month.

PMID- 28502558
TI  - Identification of candidate biomarkers that involved in the epigenetic
      transcriptional regulation for detection gastric cancer by iTRAQ based
      quantitative proteomic analysis.
AB  - BACKGROUND: The sensitivities and specificities of biomarkers for gastric cancer
      are insufficient for clinical detection, and new diagnostics are therefore
      urgently required. METHODS: A discovery set of gastric cancer tissues was labeled
      with iTRAQ reagents, separated using SCX chromatography, and identified using LC
      ESI-MS/MS. A validation set of gastric cancer tissues was used to confirm the
      expression levels of potential markers. RESULTS: The present study detected
      metastasis-associated protein 2 (MTA2) and Histone deacetylases 1 (HDAC1)
      proteins that were overexpressed in gastric cancer tissues compared with that in
      adjacent gastric tissue. The sensitivity and specificity of MTA2 in detecting 76
      cases gastric cancers were 57.9% (95% CI: 46.5%-69.3%) and 55.3% (95% CI: 43.8%
      66.7%), respectively. The sensitivity and specificity of HDAC1 were 61.8% (95%
      CI: 50.7%-73%) and 63.2% (95% CI: 52.1%-74.3%), respectively. The co-expression
      of MTA2 and HDAC1 in gastric cancer achieved 65.3% sensitivity (95% CI: 51.5%
      79.1%) and 65.2% specificity (95% CI: 50.9%-79.5%), which was strongly associated
      with lymph node metastasis and TNM staging. CONCLUSION: The present findings
      indicated a tight correlation between the MTA2 and HDAC1 expression level and
      lymph node metastasis and TNM staging in gastric cancers. Therefore, MTA2 and
      HDAC1 might be predictors of lymph node metastasis phenotype and possible target
      molecule for anticancer drug design in human gastric cancer.

PMID- 28502559
TI  - 3'-UTR SNP rs2229611 in G6PC1 affects mRNA stability, expression and Glycogen
      Storage Disease type-Ia risk.
AB  - The frequency of rs2229611, previously reported in Chinese, Caucasians, Japanese
      and Hispanics, was investigated for the first time in Indian ethnicity. We
      analyzed its role in the progression of Glycogen Storage Disease type-Ia (GSD-Ia)
      and breast cancer. Genotype data on rs2229611 revealed that the risk of GSD-Ia
      was higher (P=0.0195) with CC compared to TT/TC genotypes, whereas no such
      correlation was observed with breast cancer cases. We observed a strong linkage
      disequilibrium (LD) among rs2229611 and other disease causing G6PC1 variants
      (|D'|=1, r2=1). Functional validation performed in HepG2 cells using luciferase
      constructs showed significant (P<0.05) decrease in expression than wild-type 3'
      UTR due to curtailed mRNA stability. Furthermore, AU-rich elements (AREs)
      mediated regulation of G6PC1 expression characterized using 3'-UTR deletion
      constructs showed a prominent decrease in mRNA stability. We then examined
      whether miRNAs are involved in controlling G6PC1 expression using pmirGLO-UTR
      constructs, with evidence of more distinct inhibition in the reporter function
      with rs2229611. These data suggests that rs2229611 is a crucial regulatory SNP
      which in homozygous state leads to a more aggressive disease phenotype in GSD-Ia
      patients. The implication of this result is significant in predicting disease
      onset, progression and response to disease modifying treatments in patients with
      GSD-Ia.

PMID- 28502560
TI  - A microscale protocol for the isolation of transferrin directly from serum.
AB  - A microscale procedure for the isolation of transferrin directly from human serum
      (hTf) is described in this study. The protocol is based on three precipitation
      steps without application of chromatography. It lasts 90min with the initial
      sample volume of 250MUL. The yield of the isolated hTf is 58%, which is
      considerable in biochemical terms. The purity of the isolated hTf is 97%, as
      assessed by three methods: electrophoresis followed by protein staining,
      immunoblotting and HPLC. Immunoblotting with antibodies against other major serum
      proteins indicated that isolated hTf does not contain albumin, immunoglobulin G
      or alpha-2-macroglobulin. Lectin dot-blot demonstrated that isolated hTf
      preserved its glycan moieties. Fluorescent emission spectroscopy of the isolated
      hTf has shown no changes in tertiary structure. Isolated hTf was approximately
      26% saturated with iron ion, which is comparable to physiological value (although
      a degree of saturation decreases to some extent during isolation procedure).
      Finally, co-immunoprecipitation experiment confirmed that isolated hTf retained
      its ligand characteristics crucial for the ligand-receptor type of interaction
      with the hTf receptor. To conclude, the procedure described in this work, is time
      and cost-effective, allows multiple sample handling and provides high-purity hTf
      isolate with preserved structural and functional properties.

PMID- 28502561
TI  - Acute hydrocephalus due to a primary malignant peripheral nerve sheath tumor of
      the cervicothoracic junction: A case report and review of the literature.
AB  - BACKGROUND: The estimated incidence of malignant nerve sheath tumors is 0.001%
      per year, and only 2-3% of those tumors involve the spinal nerves. We present a
      rare case of acute hydrocephalus caused by primary malignant peripheral nerve
      sheath tumor of the cervicothoracic junction. CASE DESCRIPTION: A 29-year-old
      previously healthy male patient, except for a history of two previous surgeries
      for ulnar nerve entrapment and progressive left upper extremity weakness,
      presented with acute onset somnolence. The CT and MRI revealed hydrocephalus and
      periventricular edema. The patient underwent ventriculoperitoneal shunt surgery.
      Postoperative MRI of the spine revealed a 6*3*3cm intra-extradural lesion at C7
      T1 level and multiple metastases in other spinal segments. The patient underwent
      combined surgical excision and the tumor was diagnosed as a malignant peripheral
      nerve sheath tumor based on pathological and immunohistological findings.
      Radiation therapy and chemotherapy were initiated. CONCLUSION: Primary malignant
      peripheral nerve sheath tumor of the spine is a very aggressive tumor with a very
      high recurrence rate, significant potential for metastasis and very poor overall
      prognosis. They may present with features of more frequent diseases, such as
      peripheral neuropathies and may be overlooked as in our case. Thus, suspected
      cases should undergo a more detailed examination.

PMID- 28502562
TI  - Grade 1 Spetzler and Martin cerebral ruptured arteriovenous malformations treated
      by microsurgery: Poor functional outcome is related to injury from haemorrhage.
AB  - INTRODUCTION: Ruptured arteriovenous malformations (rAVM) are life-threatening
      diseases. OBJECTIVE: To evaluate the outcome of patients with grade 1 SPM rAVM
      after microsurgical treatment. MATERIALS AND METHOD: We retrospectively included
      64 consecutive operated patients with a grade 1 SPM rAVM in our institution
      between 2002 and 2012. Complications related to the surgical procedure were
      recorded. All patients were re-evaluated 3months after treatment using the
      modified Rankin Scale score (mRS). Persistent neurological disorders were
      evaluated 1year after bleeding. Conventional cerebral angiography was performed
      for each patient immediately after surgical treatment and 1year later. RESULTS:
      The mean age at diagnosis was 30.8 years. Initial WFNS score was grade 1 in 25
      patients, grade 2 in 11 patients, grade 3 in 10 patients, grade 4 in 9 patients
      and grade 5 in 9 patients. No remnant was left and a new surgery was performed
      only in a single patient who was initially operated-on under emergency conditions
      with limited preoperative investigations due to a poor clinical grade. Early
      postoperative complications related to the surgical procedure were recorded in 7
      patients. The mRS score 3months after treatment was <=2 in 53 patients (83%).
      Persistent neurological disorders were recorded in 40 patients (62.5%). High
      initial WFNS score (>2) and the hydrocephalus were significantly associated
      (P<0.05) to a bad functional outcome (mRS>2). CONCLUSION: Grade 1 rAVM is a life
      threatening disease concerning in most cases young patients. Long-term morbidity
      is often related to the hemorrhagic brain damage and rarely to the AVM resection.

PMID- 28502563
TI  - [Is the right hemisphere really minor? Involvement in the repair of bodily
      injury].
AB  - An appraisal mission regarding the repair of physical injury is based on the
      classification of the effects of injury and scales. These scales are surprisingly
      incomplete concerning the symptoms due to a right hemisphere injury. However,
      these symptoms can cause an important handicap in numerous activities, social,
      affective and professional. This paper reviews the recent functional anatomic
      knowledge of the right hemisphere functions, visuo-spatial cognition, intentional
      process and social cognition. The impacts of this appraisal data, as well as
      suggestions for new scales, are outlined.

PMID- 28502564
TI  - [Changes in the epidemiology of Spina Bifida in France in the last 30 years].

PMID- 28502565
TI  - [Management of postoperative complications in cases of Gorham's disease with
      cervical spine involvement: A case report].
AB  - Gorham's disease is a rare osteolytic bone disease, caused by pathological
      vascular tissue, which may spread to adjacent organs. It is a disease of unknown
      etiology, primarily involving the axial skeleton and whose treatment is not
      codified. Cervical spine involvement is unusual. Stabilization of the cervical
      spine is a real surgical challenge. We report the case of a young adult treated
      in our neurosurgery department for a cervical spine localization of Gorham's
      disease.

PMID- 28502566
TI  - Lateral skull base chondroblastoma resected with facial nerve posterior
      transposition.
AB  - INTRODUCTION: Chondroblastoma is a rare tumor that can involve the temporal bone.
      Because it is a benign tumor, functional surgery must be proposed. We report a
      case of a patient with a massive chondroblastoma operated on with preservation of
      the facial nerve, and description of the surgical technique. CASE PRESENTATION: A
      37-year-old man presented with a 9-month history of a growing left pre-auricular
      mass and hearing loss. Neuroimaging showed an osteolytic mass invading the
      temporal bone and temporomandibular joint. Excision was performed via a
      transpetrosal and transcochlear approach with posterior transposition of the
      facial nerve. EMG monitoring was effective in preventing facial palsy. Four years
      later, no sign of recurrence was observed. DISCUSSION: Chondroblastoma is a
      locally aggressive tumor, especially when located in the petrous bone and
      temporomandibular joint. The suggested treatment is a complete excision.

PMID- 28502567
TI  - Myelopathy secondary to a spinal cord compression induced by C2 nerve tumors
      during head rotation.
AB  - INTRODUCTION: It is well known that nerve root tumors developing in the spinal
      canal can be responsible for spinal cord compression leading to myelopathy and
      neurological deficits. We report the case of a patient with bilateral C2
      neurofibromas presenting with a myelopathy of the upper cervical spine with no
      spinal cord compression on standard magnetic resonance imaging. The spinal cord
      compression occurred between the cervical neurofibromas only during head
      rotation. CASE REPORT: A patient with bilateral neurofibromas of the C2 nerve
      roots showed a progressive neurological deterioration with an intramedullary MRI
      hypersignal without visible compression. Only an additional MRI carried-out with
      the head in rotation demonstrated the tumoral dynamic compression. A review of
      the literature showed that only two similar cases had previously been reported.
      The largest C2 tumor was completely removed uneventfully. CONCLUSION: Dynamic
      compression of the spinal cord in patients with bilateral C2 nerve root tumors
      must be routinely investigated even if the standard MRI shows no compression.

PMID- 28502568
TI  - Resection of cavernous angioma located in eloquent areas using functional
      cortical and subcortical mapping under awake conditions. Outcomes in a 50-case
      multicentre series.
AB  - INTRODUCTION: Surgical resection of supratentorial cavernous angiomas located in
      eloquent areas poses a significant risk to the patient of postoperative
      neurological impairment and justifies intraoperative functional monitoring.
      METHODS: Multicentre retrospective series of adult patients with cavernous
      angiomas located within eloquent areas and treated with functional-based surgical
      resection according to functional boundaries under intraoperative functional
      cortico-subcortical monitoring under awake conditions. RESULTS: Fifty patients
      (18 males, mean 36.3+/-10.8 year-old) underwent surgical resection with
      intraoperative cortico-subcortical functional mapping using direct
      electrostimulation under awake conditions for a cavernous angioma located in
      eloquent areas with a mean postoperative follow-up of 21.0+/-21.2 months. At
      presentation, the cavernous angioma had previously resulted in severe impairment
      (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%,
      reduced Karnofsky Performance Status score of 70 or less in 24%, inability to
      work in 52%). Functional-based surgical resection allowed complete removal of the
      cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative
      seizures and other complications were rare, and similarly so across all centres
      included in this series. Postoperatively, we found functional improvement in 84%
      of patients (reduced Karnofsky Performance Status score of 70 or less in 6%,
      uncontrolled seizures in 16%, and inability to work in 11%). CONCLUSION:
      Functional-based surgical resection aids the safe and complete resection of
      cavernous angiomas located in eloquent areas while minimizing the surgical risks.
      Functional mapping has to be considered in such challenging cases.

PMID- 28502569
TI  - An In Vitro Comparison Study of the Use of a Drill or a Saw in the Hunsuck-Dal
      Pont Modification of the Obwegeser Sagittal Split Osteotomy in Pig Mandibles.
AB  - PURPOSE: Fracture lines in unfavorable locations are referred to as "bad splits"
      in a mandibular sagittal split osteotomy (SSO). Several modifications of the
      technique by Obwegeser have been introduced to minimize this risk. This in vitro
      study was performed to determine whether the shape of the osteotomy cut affects
      the torque and the fracture pattern of an SSO in pig mandibles. MATERIALS AND
      METHODS: In a split-mouth model, 16 mandibles were split according to the Hunsuck
      Dal Pont modification of the Obwegeser technique. Using an oscillating saw, sharp
      edged osteotomies were created on one side of the mandible and round-edged
      osteotomies were created on the contralateral side using a Lindemann bur. Torque
      forces were measured during the splitting, and the lingual fracture pattern of
      each split was classified. RESULTS: Torque forces were significantly (P < .05 by
      paired t test) decreased by 0.77 N-m (15.6%) when a saw was used for the
      osteotomy. In the 2 groups, fractures were produced along the mandibular canal.
      The mandible was more often completely fractured, including the lower mandibular
      border, when the fracture was created with an oscillating saw (P = .06 by Pearson
      chi2 test). No correlation was found between the torque used and the fracture
      pattern. CONCLUSION: Compared with round-edged osteotomies, sharp-edged
      osteotomies in pig mandibles facilitated the Hunsuck-Dal Pont modification of the
      Obwegeser sagittal splitting procedure and produced predictable results with
      decreased torque.

PMID- 28502570
TI  - A comparison of short term radiological alignment outcomes of the patient
      specific and standard instrumentation for primary total knee arthroplasty: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to review the radiological alignment
      outcomes of patient Specific (PS) cutting blocks and Standard Instrumentation in
      Primary Total Knee Arthroplasty. METHODS: We hypothesized that the use of PS
      techniques would significantly improve sagittal, coronal and rotational alignment
      of the prosthesis on short term. We performed a systematic review and a meta
      analysis including all the randomised controlled trials (RCT) using PS and
      standard (ST) total knee arthroplasty to date. RESULTS: A total of 538 PS TKA and
      549 ST TKA were included in the study. Statistical analysis of the outliers for
      femoral component sagittal, coronal and rotational positioning, tibial component
      sagittal and coronal positioning and the overall mechanical axis were assessed.
      We found that there was no significant benefit from using PS instrumentation in
      primary knee arthroplasty to aid in the positioning of either the tibial or
      femoral components. Furthermore sagittal plane tibial component positioning was
      worse in the PS than the traditional ST group. CONCLUSION: Our results suggest
      that at present PS instrumentation is not superior to ST instrumentation in
      primary total knee arthroplasty. LEVEL OF EVIDENCE: Level 1, Systematic review of
      therapeutic studies.

PMID- 28502571
TI  - Opening Life's Gifts: Facing Death for a Second Time.
AB  - Prior to the development of effective antiretroviral therapy, persons diagnosed
      with HIV thought they were going to die. Now, long-term survivors are
      contemplating death again as they age and develop other chronic diseases. The
      purpose of our study was to understand the experiences of adults living with HIV
      for 20 or more years as they faced death for a second time. Hermeneutic
      phenomenology guided the research as participants shared their lived experience
      through storytelling. Each person's story was audiotaped and transcribed
      verbatim. Transcript analysis occurred as data were collected. Three common
      themes from the narratives were identified: Making Choices, Transformation of
      Fear, and Meaning of Death. Positive and negative pathways influenced each
      participants' decision-making. Over time, fear of dying was transformed and
      energy was directed toward living. Even though the participants in this study
      were facing death again, they recognized it as a natural part of life.

PMID- 28502572
TI  - "It Was a Learning Experience": Lessons Learned From Young African American Men
      and Women's Sexual Debut.

PMID- 28502573
TI  - Diverse acidogenic effluents as feedstock for microalgae cultivation: Dual phase
      metabolic transition on biomass growth and lipid synthesis.
AB  - In this study, a biorefinery process integrating dark fermentation with
      microalgae cultivation (dual phase metabolic transition) was demonstrated with
      real-field wastewater. Acid rich fermented effluents (distillery waste (FDW1);
      dairy waste (FDW2)) were used as feedstock for microalgae cultivation.
      Experiments were performed with FDW1 during growth phase (GP) in mixotrophic mode
      and FDW2 during stress phase (SP) in both mixotrophic and heterotrophic modes.
      Mixotrophic cultivation with FDW1 documented significantly higher biomass
      productivity (5.3g/l). Total lipid (TL) percentage was high in mixotrophic (34%)
      mode and neutral lipid (NL) was high in heterotrophic (13%) mode of cultivation
      during SP with FDW2. Overall, the microalgae growth is favoured with effluents
      containing high acetate, and low butyrate concentrations. Mixotrophic cultivation
      enhanced both biomass growth and lipid production along with simultaneous
      treatment.

PMID- 28502574
TI  - DINeR: Database for Insect Neuropeptide Research.
AB  - Neuropeptides are responsible for regulating a variety of functions, including
      development, metabolism, water and ion homeostasis, and as neuromodulators in
      circuits of the central nervous system. Numerous neuropeptides have been
      identified and characterized. However, both discovery and functional
      characterization of neuropeptides across the massive Class Insecta has been
      sporadic. To leverage advances in post-genomic technologies for this rapidly
      growing field, insect neuroendocrinology requires a consolidated, comprehensive
      and standardised resource for managing neuropeptide information. The Database for
      Insect Neuropeptide Research (DINeR) is a web-based database-application used for
      search and retrieval of neuropeptide information of various insect species
      detailing their isoform sequences, physiological functionality and images of
      their receptor-binding sites, in an intuitive, accessible and user-friendly
      format. The curated data includes representatives of 50 well described
      neuropeptide families from over 400 different insect species. Approximately 4700
      FASTA formatted, neuropeptide isoform amino acid sequences and over 200 records
      of physiological functionality have been recorded based on published literature.
      Also available are images of neuropeptide receptor locations. In addition, the
      data include comprehensive summaries for each neuropeptide family, including
      their function, location, known functionality, as well as cladograms, sequence
      alignments and logos covering most insect orders. Moreover, we have adopted a
      standardised nomenclature to address inconsistent classification of
      neuropeptides. As part of the H2020 nEUROSTRESSPEP project, the data will be
      actively maintained and curated, ensuring a comprehensive and standardised
      resource for the scientific community. DINeR is publicly available at the project
      website: http://www.neurostresspep.eu/diner/.

PMID- 28502575
TI  - National assessment of HPV and Pap tests: Changes in cervical cancer screening,
      National Health Interview Survey.
AB  - BACKGROUND: Major organizations recommend cytology screening (Pap test) every
      3years for women aged 21-65; women aged 30 to 65 have the option of adding the
      HPV test (co-test) every 5years. We examined national percentages of cervical
      cancer screening, and we examined use of co-testing as an option for screening.
      METHODS: We used 2015 U.S. National Health Interview Survey (NHIS) data to
      examine recent cervical cancer screening (Pap test within 3years among women aged
      21-65 without a hysterectomy; N=10,596) and co-testing (N=9,125). We also
      conducted a multivariable analysis to determine odds of having had a Pap test or
      co-test by demographic variables. To evaluate changes in screening over time, we
      examined Pap testing during the years 2000, 2005, 2008, 2010, 2013 and 2015.
      Analysis completed in Atlanta, GA during 2016. RESULTS: Overall, 81.1% of
      eligible women reported having a Pap test within 3years; percentages declined
      over time among all age groups. An estimated 14 million women aged 21-65 had not
      been screened within the past 3years. Recent immigrants to the United States,
      women without insurance, and women without a usual source of healthcare had lower
      odds of being up to date with screening. About 1/3 of women up to date on Pap
      testing reported having a co-test with their most recent Pap test. CONCLUSIONS:
      Declines in screening among women aged 21-65 are cause for concern. More research
      is needed on co-testing practices. Provider and patient education efforts may be
      needed to clarify recommended use of HPV tests.

PMID- 28502576
TI  - The effect of MPOWER scores on cigarette smoking prevalence and consumption.
AB  - BACKGROUND: The World Health Organization (WHO) introduced the MPOWER package to
      support policy implementation under the Framework Convention on Tobacco Control
      (FCTC). This study examined the effect of MPOWER policies on smoking prevalence
      and cigarette consumption in a global context. METHODS: The MPOWER composite
      score was constructed by adding up the six MPOWER scores for each country and
      survey year 2007-2008, 2010, 2012, and 2014, with a possible range between 6 (1
      in each of the six score) and 29 (4 in M score and 5 in POWER scores). MPOWER
      composite scores that measured policy implementation were then linked to
      cigarette smoking prevalence and consumption data from Euromonitor International.
      Fractional logit and OLS regressions were employed to examine the effect of the
      composite MPOWER score on adult smoking prevalence and cigarette consumption,
      respectively. RESULTS: Results indicate that a 1-unit increase in the composite
      score reduces smoking prevalence by 0.2 percentage points (p<0.05) among adults
      and 0.3 percentage points (p<0.01) among adult males; and a reduction of 23
      sticks of cigarette (1 pack of cigarettes) in cigarette consumption per capita
      per year. At this rate, if countries had implemented the MPOWER package to the
      highest levels during 2007-2014, they would have experienced a reduction in
      smoking prevalence of 7.26% among adults and 7.87% among adult males and a
      reduction of 13.80% in cigarette consumption. CONCLUSIONS: MPOWER policies were
      effective in reducing cigarette smoking among adults. Parties should continue to
      implement MPOWER policies that have been recommended by the WHO FCTC to curb
      tobacco epidemic.

PMID- 28502577
TI  - Psycho-social influences upon older women's decision to attend cervical
      screening: A review of current evidence.
AB  - Cervical cancer is the fourth most common cancer in women worldwide (WHO, 2016).
      In many developed countries the incidence of cervical cancer has been
      significantly reduced by the introduction of organised screening programmes
      however, in the UK, a fall in screening coverage is becoming a cause for concern.
      Much research attention has been afforded to younger women but age stratified
      mortality and incidence data suggest that older women's screening attendance is
      also worthy of study. This paper provides a review of current evidence concerning
      the psycho-social influences that older women experience when deciding whether to
      attend cervical screening. Few studies have focussed on older women and there are
      significant methodological issues with those that have included them in their
      samples. Findings from these studies indicate several barriers which may deter
      older women from screening, such as embarrassment and logistical issues. Drivers
      to screening include reassurance and a sense of obligation. Physical, social and
      emotional changes that occur as women age may also have an impact on attendance.
      This review concludes that there is a clear need for better understanding of the
      perceptions of older women specifically with regard to cervical cancer and
      screening. Future research should inform the design of targeted interventions and
      provision of information to enable informed decision-making regarding cervical
      screening among older women.

PMID- 28502578
TI  - Evaluation of the expect respect support group program: A violence prevention
      strategy for youth exposed to violence.
AB  - In the present study, we assess the effects of the Expect Respect Support Groups
      (ERSG) on frequency of teen dating violence (TDV) and general youth violence.
      ERSG is a school-based violence prevention program for youth who have been
      exposed to violence in their home, school, or community. Boys and girls (N=1,678,
      Mage=14.3, S.D.=1.7, Range=11-17) from 36 schools in Texas participated in this
      accelerated longitudinal (7-year trajectory) study beginning in 2011. Latent
      growth curve analyses were conducted using three waves of data from three cross
      sectional cohorts of adolescents. Among boys, the number of ERSG sessions
      attended related to incremental declines in psychological TDV perpetration and
      victimization, physical TDV victimization, sexual TDV perpetration and
      victimization, reactive aggression, and proactive aggression. Girls attending
      ERSG demonstrated reductions in reactive and proactive aggression. The present
      findings suggest ERSG may be an effective cross-cutting strategy to reduce TDV
      and other forms of violence among high-risk boys and possibly girls. This
      information provides valuable understanding of TDV and youth violence in high
      risk populations and may be useful in tailoring future prevention efforts to
      different groups of teens.

PMID- 28502579
TI  - Point-of-sale cigarette purchase patterns among U.S. adult smokers-National Adult
      Tobacco Survey, 2012-2014.
AB  - Tobacco products are ubiquitous in most U.S. retail environments. Given that data
      on preferred point-of-sale purchase locations among U.S. adult tobacco users are
      limited, an enhanced understanding of tobacco purchase locations can help inform
      tobacco control policy, planning, and practice. We investigated prevalence and
      sociodemographic characteristics associated with cigarette purchase location
      among U.S. adult smokers. Pooled data came from the 2012-2013 (N=60,192) and 2013
      2014 (N=75,233) National Adult Tobacco Surveys. Current cigarette smokers
      (n=18,005) aged >=18 were asked if they purchased cigarettes within the previous
      30days (n=15,182) and, if so, where they last purchased cigarettes. In 2016,
      logistic regression adjusted for sex, age, race/ethnicity, education level and
      annual household income was used to assess characteristics associated with
      purchase location. Among current smokers, 90.2% reported purchasing cigarettes in
      the past 30days. The most common purchase locations were convenience stores/gas
      stations (69.1%), tobacco discount stores (9.9%), drug stores (5.0%),
      supermarkets (4.9%), and liquor stores (3.6%). The odds of purchasing cigarettes
      at convenience stores/gas stations were higher among men (adjusted odds ratio
      (AOR)=1.4; 95% confidence interval (CI)=1.2-1.5) than women; and among adults
      aged 18-24 (AOR=3.1; 95% CI=2.4-3.9), 25-44 (AOR=3.1; 95% CI=2.7-3.7), and 45
      64years (AOR=1.8 95% CI=1.6-2.1) than adults aged >=65years. Over two-thirds of
      U.S. smokers last purchased cigarettes from convenience stores/gas stations.
      Understanding the relationship between purchase location and smoker
      characteristics may inform tobacco control strategies in the retail environment.

PMID- 28502580
TI  - [Non-antiretroviral drugs uses among HIV-infected persons receiving
      antiretroviral therapy in Senegal: Costs and factors associated with
      prescription].
AB  - BACKGROUND: In addition to antiretroviral therapy, non-antiretroviral drugs are
      necessary for the appropriate care of people living with HIV. The costs of such
      drugs are totally or partially supported by the people living with HIV. We aimed
      to evaluate the overall costs, the costs supported by the people living with HIV
      and factors associated with the prescription of non-antiretroviral drugs in
      people living with HIV on antiretroviral therapy in Senegal. METHODS: We
      conducted a retrospective cohort study on 331 people living with HIV who
      initiated antiretroviral therapy between 2009 and 2011 and followed until March
      2012. The costs of non-antiretroviral drugs were those of the national pharmacy
      for essential drugs; otherwise they were the lowest costs in the private
      pharmacies. Associated factors were identified through a logistic regression
      model. RESULTS: The study population was 61 % female. At baseline, 39 % of
      patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage
      4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m2 and 93
      cells/MUL, respectively. After a mean duration of 11.4 months of antiretroviral
      therapy, 85 % of patients received at least one prescription for a non
      antiretroviral drug. Over the entire study period, the most frequently prescribed
      non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %),
      vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34
      Euros and the mean cost supported per patient was 14 Euros. The most expensive
      drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents
      (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription
      for a non-antiretroviral drug was associated with advanced clinical stage (WHO
      clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type
      (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. CONCLUSION: Non
      antiretroviral drugs are frequently prescribed to people living with HIV in
      developing countries; mainly those infected with HIV-1 and those at an advanced
      clinical stage. Their costs can be a barrier to appropriate care and necessary
      efforts must made to make them available. However, early initiation of
      antiretroviral therapy and the registration of some non-antiretroviral drugs on
      the list of essential drugs, as well as social protection systems, should reduce
      their use and costs.

PMID- 28502581
TI  - Human infections with avian influenza viruses in mainland China: A particular
      risk for southeastern China.

PMID- 28502582
TI  - Upregulation of RAD51 expression is associated with progression of thyroid
      carcinoma.
AB  - AIMS: RAD51 participates in homologous recombination repair (HRR) of double
      stranded DNA breaks (DSBs) which may cause genomic instability and cancer. The
      aim of this study was to investigate RAD51 gene expression at transcriptional and
      translational levels to measure mRNA and protein level and to correlate its
      relationship with proliferation marker, Ki67 in thyroid cancer patients. This
      study also explored correlation of these genes with different clinicopathological
      parameters of the study cohort by Spearman's rank correlation coefficient.
      METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) and
      immunohistochemistry were used to detect mRNA transcript levels and protein
      expression of RAD51 and Ki67 in 102 cases of thyroid cancer tissues and equal
      number of uninvolved healthy thyroid tissue controls. RESULTS: Data showed that
      expression for both RAD51 and Ki67 was significantly increased in thyroid cancer
      (p<0.001). High RAD51 and Ki67 expression was associated with later stages, poor
      tissue differentiation, large tumor size, positive lymph node metastasis and
      distant metastasis. The correlation analysis demonstrated a strong positive
      correlation (r=0.461) between RAD51 and Ki67 on mRNA level and on protein level
      (r=0.866). Strong correlation was observed between clinicopathological
      characteristics and selected molecules. CONCLUSION: The present study concluded
      that upregulation of RAD51 and overexpression of Ki67 may be associated with the
      progression of thyroid cancer.

PMID- 28502583
TI  - Homozygous EDNRB mutation in a patient with Waardenburg syndrome type 1.
AB  - OBJECTIVE: To examine and expand the genetic spectrum of Waardenburg syndrome
      type 1 (WS1). METHODS: Clinical features related to Waardenburg syndrome (WS)
      were examined in a five-year old patient. Mutation analysis of genes related to
      WS was performed in the proband and her parents. Molecular modeling of EDNRB and
      the p.R319W mutant was conducted to predict the pathogenicity of the mutation.
      RESULTS: The proband showed sensorineural hearing loss, heterochromia iridis, and
      dystopia canthorum, fulfilling the clinical criteria of WS1. Genetic analyses
      revealed that the proband had no mutation in PAX3 which has been known as the
      cause of WS1, but had a homozygous missense mutation (p.R319W) in endothelin
      receptor type B (EDNRB) gene. The asymptomatic parents had the mutation in a
      heterozygote state. This mutation has been previously reported in a heterozygous
      state in a patient with Hirschsprung's disease unaccompanied by WS, but the
      patient and her parents did not show any symptoms in gastrointestinal tract.
      Molecular modeling of EDNRB with the p.R319W mutation demonstrated reduction of
      the positively charged surface area in this region, which might reduce binding
      ability of EDNRB to G protein and lead to abnormal signal transduction underlying
      the WS phenotype. CONCLUSIONS: Our findings suggested that autosomal recessive
      mutation in EDNRB may underlie a part of WS1 with the current diagnostic
      criteria, and supported that Hirschsprung's disease is a multifactorial genetic
      disease which requires additional factors. Further molecular analysis is
      necessary to elucidate the gene interaction and to reappraise the current WS
      classification.

PMID- 28502584
TI  - Up-regulation of miR-325-3p suppresses pineal aralkylamine N-acetyltransferase
      (Aanat) after neonatal hypoxia-ischemia brain injury in rats.
AB  - Survivors of hypoxic-ischemic brain damage (HIBD), besides impairment of
      psychomotor development, often develop circadian rhythm disorders, although the
      underlying mechanisms are largely unknown. Here, we first verified that mRNA and
      protein expression of pineal aralkylamine N-acetyltransferase (Aanat), a key
      regulator for melatonin (MT) synthesis, along with MT, were severely impaired
      after HIBD. In addition, we demonstrated that neonatal HIBD disrupted the
      circadian rhythmicity of locomotor activities in juvenile rats. Based on
      bioinformatics analysis of a high throughput screening of miRNA expression
      changes after HIBD (Ding et al., 2015), we identified one microRNA, miR-325-3p,
      as a potential candidate responsible for the down regulation of Aanat after HIBD.
      Luciferase reporter assays demonstrated a specific interaction between miR-325-3p
      and Aanat mRNA 3'-UTR. miR-325-3p blocked norepinephrine (NE) induced Aanat
      activation in cultured pinealocytes. In addition, miR-325-3p inhibition partially
      rescued Aanat induction by NE, which was significantly reduced under oxygen
      glucose deprivation. By elucidating the role of pineal miR-325-3p on Aanat
      expression upon injury, our study provides new insights into the
      pathophysiological mechanisms of circadian dysfunction and potential therapeutic
      targets after HIBD.

PMID- 28502587
TI  - Direct and indirect activation of eukaryotic elongation factor 2 kinase by AMP
      activated protein kinase.
AB  - BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key
      regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits
      eEF2, the translation factor necessary for peptide translocation during the
      elongation phase of protein synthesis. When cellular energy demand outweighs
      energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated,
      leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a
      process that consumes a large proportion of cellular energy under optimal
      conditions. AIM: The goal of the present study was to elucidate the mechanisms by
      which AMPK activation leads to increased eEF2 phosphorylation to decrease protein
      synthesis. METHODS: Using genetically modified mouse embryo fibroblasts (MEFs),
      effects of treatments with commonly used AMPK activators to increase eEF2
      phosphorylation were compared with that of the novel compound 991. Bacterially
      expressed recombinant eEF2K was phosphorylated in vitro by recombinant activated
      AMPK for phosphorylation site-identification by mass spectrometry followed by
      site-directed mutagenesis of the identified sites to alanine residues to study
      effects on the kinetic properties of eEF2K. Wild-type eEF2K and a Ser491/Ser492
      mutant were retrovirally re-introduced in eEF2K-deficient MEFs and effects of 991
      treatment on eEF2 phosphorylation and protein synthesis rates were studied in
      these cells. RESULTS & CONCLUSIONS: AMPK activation leads to increased eEF2
      phosphorylation in MEFs mainly by direct activation of eEF2K and partly by
      inhibition of mammalian target of rapamycin complex 1 (mTORC1) signaling.
      Treatment of MEFs with AMPK activators can also lead to eEF2K activation
      independently of AMPK probably via a rise in intracellular Ca2+. AMPK activates
      eEF2K by multi-site phosphorylation and the newly identified Ser491/Ser492 is
      important for activation, leading to mTOR-independent inhibition of protein
      synthesis. Our study provides new insights into the control of eEF2K by AMPK,
      with implications for linking metabolic stress to decreased protein synthesis to
      conserve energy reserves, a pathway that is of major importance in cancer cell
      survival.

PMID- 28502586
TI  - Novel zinc complexes of a non-steroidal anti-inflammatory drug, niflumic acid:
      Structural characterization, human-DNA and albumin binding properties.
AB  - Three novel Zn(II) complexes of NSAID niflumic acid (Hnif) were prepared and
      studied, namely; [Zn(MeOH)4(nif)2] (1), [Zn(cyclam)(nif)2] (2) and
      [Zn(nif)2(tmen)] (3), where nif is deprotonated niflumic acid, cyclam is 1,4,8,11
      Tetraazacyclotetradecane and tmen is N,N,N',N'-Tetramethylethylenediamine. The
      complexes have been characterized by infrared spectroscopy, elemental and thermal
      analysis and single-crystal X-ray structure analysis. All three complexes contain
      two deprotonated niflumato anions monodentately coordinated via carboxylato
      groups. Furthermore, fluorescence binding studies of the prepared compounds with
      human genomic DNA-EB (ethidium bromide) were carried out, which suggest that all
      complexes are able to bind to DNA via intercalation. Moreover, from the obtained
      results it followed that complexes 2 and 3 bind to DNA from the tissue with
      aortic aneurysm (aDNA) and control (cDNA) with a different strength.
      Additionally, complexes 1-3 exhibit good binding affinity to human serum albumin
      with high binding constant.

PMID- 28502588
TI  - Alternative uses for co-products: Harnessing the potential of valuable compounds
      from meat processing chains.
AB  - Opportunities for exploiting the inherent value of protein-rich meat processing
      co-products, in the context of increased global demand for protein and for
      sustainable processing systems, are discussed. While direct consumption maybe the
      most profitable route for some, this approach is influenced greatly by local and
      cultural traditions. A more profitable and sustainable approach may be found in
      recognizing this readily available and under-utilised resource can provide high
      value components, such as proteins, with targeted high value functionality of
      relevance to a variety of sectors. Applications in food & beverages, petfood
      biomedical and nutrition arenas are discussed. Utilization of the raw material in
      its entirety is a necessary underlying principle in this approach to help
      maintain minimum waste generation. Understanding consumer attitudes to these
      products, in particular when used in food or beverage systems, is critical in
      optimizing commercialization strategies.

PMID- 28502589
TI  - A case of a novel mutation in HNF1beta-related maturity-onset diabetes of the
      young type 5 with diabetic kidney disease complication in a Chinese family.
AB  - AIMS: Precise diagnosis of maturity-onset diabetes of the young (MODY) has proven
      valuable for understanding mechanism of diabetes and selecting optimal therapy. A
      proband and her mother with diabetic kidney disease (DKD) were studied to
      investigate potential genes responsible for diabetes and different severity of
      DKD between the parent and offspring. METHODS: The family with suspected MODY
      underwent mutational analyses by the whole exome sequencing (WES). Candidate
      pathogenic variants were validated by Sanger sequencing and tested for co
      segregation. The clinical parameters of subjects were collected from medical
      records. RESULTS: A novel missense heterozygous mutation in exon 4 of the
      hepatocyte nuclear factor 1beta (HNF1beta), c.1007A > G (p.H336R), was identified
      in both the proband and her mother. Moreover, comparing the family's WES results,
      we found that the proband had acquired a KCNQ1 gene mutation from her father and
      acquired ACE and SORBS1 gene mutations from her mother. These three genes are
      known susceptibility genes of DKD and may impose additional effects contributing
      to DKD severity. CONCLUSIONS: A novel mutation in HNF1beta-MODY was identified in
      a Chinese family complicated with DKD, and the additional effect of pathogenic
      variants in susceptibility genes was speculated to contribute to DKD severity.

PMID- 28502585
TI  - Frontoparietal neurostimulation modulates working memory training benefits and
      oscillatory synchronization.
AB  - There is considerable interest in maintaining working memory (WM) because it is
      essential to accomplish most cognitive tasks, and it is correlated with fluid
      intelligence and ecologically valid measures of daily living. Toward this end, WM
      training protocols aim to improve WM capacity and extend improvements to
      unpracticed domains, yet success is limited. One emerging approach is to couple
      WM training with transcranial direct current stimulation (tDCS). This pairing of
      WM training with tDCS in longitudinal designs promotes behavioral improvement and
      evidence of transfer of performance gains to untrained WM tasks. However, the
      mechanism(s) underlying tDCS-linked training benefits remain unclear. Our goal
      was to gain purchase on this question by recording high-density EEG before and
      after a weeklong WM training+tDCS study. Participants completed four sessions of
      frontoparietal tDCS (active anodal or sham) during which they performed a
      visuospatial WM change detection task. Participants who received active anodal
      tDCS demonstrated significant improvement on the WM task, unlike those who
      received sham stimulation. Importantly, this pattern was mirrored by neural
      correlates in spectral and phase synchrony analyses of the HD-EEG data. Notably,
      the behavioral interaction was echoed by interactions in frontal-posterior alpha
      band power, and theta and low alpha oscillations. These findings indicate that
      one mechanism by which paired tDCS+WM training operates is to enhance cortical
      efficiency and connectivity in task-relevant networks.

PMID- 28502590
TI  - Spontaneous bacterial peritonitis due to Listeria monocytogenes: Always to be
      remembered.

PMID- 28502592
TI  - Matrix metalloproteinases as regulators of inflammatory processes.
AB  - Inflammation is a central mechanism for dealing with insults to tissue, either
      from pathogenic invaders or by other damage-inducing means, such that the threat
      is removed, the tissue is healed and there is a return to homeostasis. It is a
      multi-step process with manifold methods of regulation built in. Proteolysis is
      one such regulatory method and members of the matrix metalloproteinase (MMP)
      family of proteinases have been shown to influence inflammation in myriad of
      ways. It is becoming more and more clear that no single MMP can be unequivocally
      labeled as 'good' or 'bad' when considering inflammation in general - the net
      result of proteolytic activity is dependent on context. Here we provide examples
      from recent literature, with a focus on in vivo studies, to highlight this
      concept. This article is part of a Special Issue entitled: Matrix
      Metalloproteinases edited by Rafael Fridman.

PMID- 28502594
TI  - Early evidence for a virus-like agent infecting the pest snail Theba pisana
      (Gastropoda: Pulmonata) in Southern Italy.
AB  - The Mediterranean land snail Theba pisana (Mollusca: Helicidae) is an introduced
      agricultural pest in many countries around the world, including Australia,
      Israel, USA and South Africa. In addition, this snail is an intermediate host of
      parasites of importance in both human and veterinary medicine. In this study, a
      natural population of T. pisana snails on the Domitian coast of Italy was
      surveyed following a mass mortality event. By light microscopy, 30% of the
      collected individuals showed in the calcium cells of the digestive gland the
      presence of hypertrophied nuclei containing eosinophilic to weakly basophilic
      inclusion bodies. Ultrastructural examination by transmission electron microscopy
      (TEM) showed nuclear inclusions constituted by a reticulated stroma into which
      unenveloped, roundish virus-like particles (38+/-4nm in diameter) were present.
      To the best of our knowledge this could be the first evidence for a virus-like
      agent infecting the gastropod T. pisana, which may open new biocontrol
      perspectives of the this pest worldwide.

PMID- 28502593
TI  - Meprin metalloproteases: Molecular regulation and function in inflammation and
      fibrosis.
AB  - The zinc-endopeptidases meprin alpha and meprin beta are extracellular proteases
      involved in connective tissue homeostasis, intestinal barrier function and
      immunological processes. Meprins are unique among other extracellular proteases
      with regard to cleavage specificity and structure. Meprin alpha and meprin beta
      have a strong preference for negatively charged amino acids around the scissile
      bond, reflected by cleavage sites identified in procollagen I, the amyloid
      precursor protein (APP) and the interleukin-6 receptor (IL-6R). In this review we
      report on recent findings that summarize the complex molecular regulation of
      meprins, particular folding, activation and shedding. Dysregulation of meprin
      alpha and meprin beta is often associated with pathological conditions such as
      neurodegeneration, inflammatory bowel disease and fibrosis. Based on mouse models
      and patient data we suggest meprins as possible key regulators in the onset and
      progression of fibrotic disorders, leading to severe diseases such as pulmonary
      hypertension. This article is part of a Special Issue entitled: Proteolysis as a
      Regulatory Event in Pathophysiology edited by Stefan Rose-John.

PMID- 28502591
TI  - CD8+CD28+/CD8+CD28- T cell equilibrium can predict the active stage for patients
      with inflammatory bowel disease.
AB  - BACKGROUND/AIM: The balance of blood CD8+CD28+/CD8+CD28- T cells has been
      verified to be vital for patients with ulcerative colitis (UC), but their role in
      inflammatory bowel disease (IBD) remains unknown. This investigation aimed to
      evaluate the efficiency of the balance in predicting the active stage in IBD
      patients. METHODS: Fifty-three IBD subjects, including 31 UC and 22 Crohn's
      disease (CD) patients, were enrolled, and their peripheral blood CD8+CD28+ and
      CD8+CD28- T cell levels were tested using flow cytometry. The risk factors
      related to prognosis were compared between UC and CD patients. A 1-year follow-up
      was performed for all the IBD patients, and the CD8+ T cells and their ratio were
      compared at the 3rd, 6th, 9th, and 12th months during follow-up. The sensitivity
      and specificity of the CD8+ T cell level and balance were analyzed through
      receiver operator characteristic (ROC) curves. The cumulative remission lasting
      rates (CRLRs) under the different factors were analyzed using the Kaplan-Meier
      method. RESULTS: Higher prescription rates of immunosuppressants, steroids,
      probiotics, and biological agents (BAs) were found in CD subjects in comparison
      to UC subjects (P=0.005, 0.024, 0.034, and 0.001), as was a higher active rate
      during follow-up (95.5% of CD patients vs 67.7% of UC patients, P=0.035). The
      CD8+CD28+ T cell level and the CD8+CD28+/CD8+CD28- T cell ratio were
      significantly higher in UC patients than in CD patients, but the reverse was true
      for CD8+CD28- T cells during follow-up at the 9th and 12th month (all P<0.05).
      The diagnostic models of the initial CD8+CD28+ and CD8+CD28- T cell numbers and
      the CD8+CD28+/CD8+CD28- T cell ratio in predicting the active stage were found to
      be significant, with areas under the curves (AUCs) of 0.883, 0.098, and 0.913 for
      UC subjects (with 95% CI: 0.709-0.940, 0.009-0.188, and 0.842-1.003; P=0.001,
      0.00, and 0.000) and 0.812, 0.078, and 0.898 for CD subjects (with 95% CI: 0.683
      0.957, 0.003-0.158, and 0.837-0.998; P=0.003, 0.00, and 0.000). The cut-off
      values showed that when the ratios were 1.30 for UC and 1.22 for CD patients, the
      best sensitivity and specificity were observed, with 91.6% and 89.0% for UC and
      88.5% and 85.1% for CD, respectively. The CRLRs were significantly higher in
      female, non-BA-treated, non-surgical IBD subjects when compared to male, BA
      treated, surgical subjects (P=0.031, 0.000, and 0.000). The number of CD8+CD28+
      and CD8+CD28- T cells and the CD8+CD28+/CD8+CD28- T cell ratio were correlated
      with BA treatment and surgery (all P<0.05). CONCLUSION: The CD8+CD28+/CD8+CD28- T
      cell balance, expected to be a novel immunologic marker, presented a satisfactory
      efficiency with high sensitivity and specificity in predicting the active stage
      in UC and CD patients, and the balance was closely related to the use of BAs and
      surgery.

PMID- 28502595
TI  - A sustained increase of plasma fibrinogen in sudden sensorineural hearing loss
      predicts worse outcome independently.
AB  - OBJECTIVES: A number of etiologies of idiopathic sudden sensorineural hearing
      loss (ISSNHL) have been proposed. Vascular disturbance is one cause of ISSNHL and
      has been reported to be associated with fibrinogen. We aimed to determine whether
      hyperfibrinogenemia is associated with poor outcome and whether a serial change
      in fibrinogen level is associated with outcome. METHODS: Twenty-two patients with
      ISSNHL were enrolled. We compared the levels of fibrinogen in ISSNHL groups
      classified as improved and non-improved according to improvement of hearing.
      Blood samples were also collected from patients who visited the emergency room
      with coronary heart disease (CHD) as the control group. RESULTS: Initial
      fibrinogen level was significantly different between the non-improved and
      improved ISSNHL group (350.63+/-87.20 vs. 310.71+/-81.06. The improved ISSNHL
      group showed a "surge phenomenon", in which fibrinogen started to decrease at day
      5 and increased at day 26. In the non-improved group, fibrinogen remained
      elevated throughout the course of therapy. CONCLUSION: It is important to measure
      not only the initial fibrinogen level but also to monitor its change throughout
      the course of therapy in order to predict the outcome of ISSNHL.

PMID- 28502597
TI  - Determining Resident Sleep During and After Call With Commercial Sleep Monitoring
      Devices.
AB  - OBJECTIVE: To demonstrate that commercial activity monitoring devices (CAMDs) are
      practical for monitoring resident sleep while on call. Studies that have directly
      monitored resident sleep are limited, likely owing to both cost and difficulty in
      study interpretation. The advent of wearable CAMDs that estimate sleep presents
      the opportunity to more readily evaluate resident sleep in physically active
      settings and "home call," a coverage arrangement familiar to urology programs.
      METHODS: Twelve urology residents were outfitted with Fitbit Flex devices during
      "home call" for a total of 57 (out of 64, or 89%) call or post-call night pairs.
      Residents were surveyed with the Stanford Sleepiness Scale (SSS), a single
      question alertness survey. Time in bed (TIB) was "time to bed" to "rise for day."
      Fitbit accelerometers register activity as follows: (1) not moving; (2) minimal
      movement or restless; or (3) above threshold for accelerometer to register steps.
      Total sleep time (TST) was the number of minutes in level 1 activity during TIB.
      Sleep efficiency (SE) was defined as TST divided by TIB. RESULTS: While on call,
      10 responding (of 12 available, 83%) residents on average reported TIB as 347
      minutes, TST as 165 minutes, and had an SE of 47%. Interestingly, SSS responses
      did not correlate with sleep parameters. Post-call sleep demonstrated increases
      in TIB, SE, and TST (+23%, +15%, and +44%, respectively) while sleepiness was
      reduced by 22%. CONCLUSION: We demonstrate that urologic residents can
      consistently wear CAMDs while on home call. SSS did not correlate with Fitbit
      estimated sleep duration. Further study with such devices may enhance sleep
      deprivation recognition to improve resident sleep.

PMID- 28502596
TI  - Safety Profile of Collagenase Clostridium Histolyticum Stratified by Degree of
      Penile Curvature in Patients With Peyronie Disease.
AB  - OBJECTIVE: To examine the safety of collagenase clostridium histolyticum (CCH) in
      adult men with penile curvature deformity <30 degrees . CCH is indicated for
      treatment of Peyronie disease in adult men with palpable plaque and a penile
      curvature deformity >=30 degrees  at start of therapy; however, during treatment,
      patients may receive CCH injections when penile curvature deformity is <30
      degrees . MATERIALS AND METHODS: Patients who received >=2 CCH treatment cycles
      in 2 phase 3 studies (Investigation for Maximal Peyronie's Reduction Efficacy and
      Safety Studies I and II) were included. All patients had penile curvature >=30
      degrees  at the beginning of treatment and could receive up to 4 treatment
      cycles. The rate and number of treatment-related adverse events (TRAEs) with CCH
      treatment were compared between patients with penile curvature deformity >=30
      degrees  and penile curvature <30 degrees . RESULTS: The number of CCH treatment
      cycles included in the current analysis totaled 1204 and 289 cycles in patients
      with penile curvature deformity >=30 degrees  and <30 degrees , respectively. The
      incidence of most TRAEs was similar between groups. Rates of penile swelling
      (21.1% vs 14.5%, P = .007), penile hemorrhage (12.8% vs 8.9%; P = .046), and skin
      hyperpigmentation (1.0% vs 0.1%; P = .025) were significantly higher in the <30
      degrees  group. The occurrence of serious TRAEs was similar between groups.
      CONCLUSION: No clinically meaningful differences were observed with TRAE rates
      when CCH injections were administered at penile curvature deformity >=30 degrees 
      vs CCH injections at penile curvature deformity <30 degrees . These findings
      highlight the safety of continued CCH injections for patients who have achieved
      penile curvature deformity <30 degrees  after an initial treatment cycle of CCH.

PMID- 28502598
TI  - Botryoid Wilms Tumor in a 2-Year-old Boy: A Case Report.
AB  - We report a case of botryoid Wilms tumor that occupied the renal pelvis. A 2-year
      old boy was referred to us with a chief complaint of macrohematuria.
      Ultrasonography, computed tomography, and magnetic resonance imaging showed a
      tumor occupying the left renal pelvis. Radical nephroureterectomy was performed.
      The resected specimen showed a botryoid sarcoma-like appearance, with a pedicle
      attaching to the pelvicalyceal wall, occupying the left renal pelvis. Histologic
      findings confirmed botryoid Wilms tumor. Postoperative adjuvant chemotherapy was
      executed. There was no recurrence or metastasis 6 months after
      nephroureterectomy.

PMID- 28502599
TI  - A Novel Retrieval Technique for Ureteral Stents Under Ultrasound Guidance in Male
      Patients.
AB  - OBJECTIVE: To simply retrieve double-J stents in male patients under ultrasound
      guidance, a novel technique is developed and evaluated for efficiency, safety,
      and tolerability. METHODS: Fifty-six male patients, ranging in age from 23 to 65
      years old, were recruited from March to December 2015. Thirty patients (32
      stents) underwent double-J stent retrieval by ultrasound guidance and 26 patients
      (28 stents) underwent cystoscopy retrieval separately. Clinical outcomes were
      compared between groups. Hematuria and leukocytosis were assessed every day
      postoperatively. A visual analog pain scale on a scale of 0-10 was used to assess
      procedure-related pain. RESULTS: In the experimental group, 87.5% of ureteral
      stents were successfully removed. Using our novel technique without any local
      anesthesia, male patients experienced less pain compared with the cystoscopy
      group significantly (P < .001). The majority of complications were microscopic
      hematuria (39.28%), less than that in the cystoscopy group (69.23%, P = .027).
      Meanwhile, only few patients have leukocytosis in both groups (14.3% vs 11.5%, P
      > .05). Average procedure time was 7.35 +/- 2.59 minutes longer than that of the
      standard group (5.13 +/- 1.29 minutes; P < .001). However, it had been improved
      with increasing experience (r = 0.618, P < .001). In addition, this novel
      technique is cost-effective for clinical practice. CONCLUSION: This is the first
      study to assess the possibility of ultrasound-guided retrieval technique in male
      patients. The safety and success rate of this new technique is similar to that of
      a conventional procedure. Whereas it is tolerable and cost effective for male and
      disabled patient bear with lithotomy position.

PMID- 28502600
TI  - The puzzling question of inhibitory control in Tourette syndrome: A meta
      analysis.
AB  - Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic
      tics. Inhibitory control is a key issue in TS, and many disruptive or impulsive
      behaviors might arise from inhibitory deficits. However, conflicting findings
      regarding TS patients' inhibitory performance in neuropsychological tasks have
      been reported throughout the literature. Therefore, this meta-analysis aimed to
      evaluate inhibitory control through neuropsychological tasks, and to analyze the
      factors modulating inhibitory deficits. To this end, a literature search was
      performed through MEDLINE and PsycINFO, to retrieve studies including
      neuropsychological tasks that assessed inhibitory control in TS patients. Of the
      4020 studies identified, 61 were included in the meta-analysis, for a total of
      1717 TS patients. Our analyses revealed a small to medium effect in favor of
      inhibitory deficits in TS patients. This effect was larger in TS+ADHD patients,
      but pure TS patients also showed some inhibitory deficits. Therefore, deficits in
      inhibitory control seem to be an inherent component of TS, and are exacerbated
      when ADHD is concomitant.

PMID- 28502601
TI  - Recycling of spent lithium-ion battery with polyvinyl chloride by mechanochemical
      process.
AB  - In the present study, cathode materials (C/LiCoO2) of spent lithium-ion batteries
      (LIBs) and waste polyvinyl chloride (PVC) were co-processed via an innovative
      mechanochemical method, i.e. LiCoO2/PVC/Fe was co-grinded followed by water
      leaching. This procedure generated recoverable LiCl from Li by the dechlorination
      of PVC and also generated magnetic CoFe4O6 from Co. The effects of different
      additives (e.g. alkali metals, non-metal oxides, and zero-valent metals) on (i)
      the conversion rates of Li and Co and (ii) the dechlorination rate of PVC were
      investigated, and the reaction mechanisms were explored. It was found that the
      chlorine atoms in PVC were mechanochemically transformed into chloride ions that
      bound to the Li in LiCoO2 to form LiCl. This resulted in reorganization of the Co
      and Fe crystals to form the magnetic material CoFe4O6. This study provides a more
      environmentally-friendly, economical, and straightforward approach for the
      recycling of spent LIBs and waste PVC compared to traditional processes.

PMID- 28502602
TI  - Uncontacted tire explosion causing trauma to bilateral lower extremities: A case
      report.
AB  - It is uncommon for tire explosion related injuries on the lower extremity. The
      bilateral lower extremities were injured by tire explosion when the patient was
      seated in a bus. She sustained an open fracture with partial bone loss in the
      right calcaneus (a comminuted fracture in the right ankle joint) and a closed
      comminuted fracture in the left tibia and fibula. This damage was caused by
      uncontacted tire explosion, thanks to a thick floor between the exploded tire and
      the patient's feet. This type of injury on lower extremity caused by uncontacted
      tire explosion was uncommon.

PMID- 28502603
TI  - Alcohol consumption for simulated driving performance: A systematic review.
AB  - PURPOSE: Alcohol consumption can lead to risky driving and increase the frequency
      of traffic accidents, injuries and mortalities. The main purpose of our study was
      to compare simulated driving performance between two groups of drivers, one
      consumed alcohol and the other not consumed, using a systematic review. METHODS:
      In this systematic review, electronic resources and databases including Medline
      via Ovid SP, EMBASE via Ovid SP, PsycINFO via Ovid SP, PubMed, Scopus, Cumulative
      Index to Nursing and Allied Health Literature (CINHAL) via EBSCOhost were
      comprehensively and systematically searched. The randomized controlled clinical
      trials that compared simulated driving performance between two groups of drivers,
      one consumed alcohol and the other not consumed, were included. Lane position
      standard deviation (LPSD), mean of lane position deviation (MLPD), speed, mean of
      speed deviation (MSD), standard deviation of speed deviation (SDSD), number of
      accidents (NA) and line crossing (LC) were considered as the main parameters
      evaluating outcomes. After title and abstract screening, the articles were
      enrolled for data extraction and they were evaluated for risk of biases. RESULTS:
      Thirteen papers were included in our qualitative synthesis. All included papers
      were classified as high risk of biases. Alcohol consumption mostly deteriorated
      the following performance outcomes in descending order: SDSD, LPSD, speed, MLPD,
      LC and NA. Our systematic review had troublesome heterogeneity. CONCLUSION:
      Alcohol consumption may decrease simulated driving performance in alcohol
      consumed people compared with non-alcohol consumed people via changes in SDSD,
      LPSD, speed, MLPD, LC and NA. More well-designed randomized controlled clinical
      trials are recommended.

PMID- 28502604
TI  - Death due to fracture of thin calvarial bones after a fall: A forensic approach.
AB  - A 45-year-old male was autopsied. He had fallen backwards from a two-stairs
      height to the ground and passed away. A skull fracture was detected in the left
      occipital area, extending up to the left side of the skull base. The patient's
      death occurred due to the very low thickness of the calvarial bones, which led to
      the aforementioned fracture, and in turn resulted in subarachnoid hemorrhage and
      death. The cortical thickness was measured and compared with average values at
      standardized points. Uniform bone thinning was confirmed rather than localized.
      Calvarial thinning may result from various conditions. In the present case study,
      however, the exact mechanism which led to the low thickness of the calvarial
      bones of the patient is undetermined. Death due to the susceptible structure and
      fracture of calvarial bones has rarely been reported throughout relevant
      literature.

PMID- 28502606
TI  - Provider Perspectives Regarding Resuscitation Decisions for Neonates and Other
      Vulnerable Patients.
AB  - OBJECTIVES: To use structured surveys to assess the perspectives of pediatric
      residents and neonatal nurses on resuscitation decisions for vulnerable patients,
      including neonates. STUDY DESIGN: Pediatric providers were surveyed using
      scenarios for 6 critically ill patients of different ages with outcomes
      explicitly described. Providers were asked (1) whether resuscitation was in each
      patient's best interest; (2) whether they would accept families' wishes for
      comfort care (no resuscitation); and (3) to rank patients in order of priority
      for resuscitation. In a structured interview, each participant explained how they
      evaluated patient interests and when applicable, why their answers differed for
      neonates. Interviews were audiotaped; transcripts were analyzed using thematic
      analysis and mixed methods. RESULTS: Eighty pediatric residents and neonatal
      nurses participated (response rate 74%). When making life and death decisions,
      participants considered (1) patient characteristics (96%), (2) personal
      experience/biases (85%), (3) family's wishes and desires (81%), (4) disease
      characteristics (74%), and (5) societal perspectives (36%). These factors were
      not in favor of sick neonates: of the participants, 85% reported having negative
      biases toward neonates and 60% did not read, misinterpreted, and/or distrusted
      neonatal outcome statistics. Additional factors used to justify comfort care for
      neonates included limited personhood and lack of relationships/attachment (73%);
      prioritization of family's best interest, and social acceptability of death
      (36%). When these preconceptions were discussed, 70% of respondents reported they
      would change their answers in favor of neonates. CONCLUSIONS: Resuscitation
      decisions for neonates are based on many factors, such as considerations of
      personhood and family's interests (that are not traditional indicators of
      benefit), which may explain why decision making is different for the neonatal
      population.

PMID- 28502605
TI  - Transphyseal separation of the distal humerus in newborns.
AB  - Obstetric traumatic separation of the distal humeral epiphysis is a very uncommon
      injury, which presents a diagnostic challenge. These case serials reviewed the
      functional outcomes of 5 patients who had sustained a fracture-separation of the
      distal humeral epiphysis at birth. The diagnosis was made at a mean time of 40.8
      h after delivery. All the patients were treated with gentle close manipulation,
      reduction under fluoroscopy and above-elbow cast application. After discharge,
      the patients were followed up for a mean of 30 months. Clinico-radiological
      results were excellent in four patients. One case necessitated closed reduction
      and percutaneous K-wire fixation at one week follow-up due to failed reduction.
      Cubitusvarus deformity was the only complication noted in 1 case. Good functional
      outcome can be expected in newborns with fracture-separation of the distal
      humeral epiphysis wherein the physis is anatomically reduced.

PMID- 28502607
TI  - Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic
      Subjects.
AB  - OBJECTIVE: To evaluate the serum levels of zonulin, which regulates tight
      junctions between enterocytes and is a physiological modulator controlling
      intestinal permeability, in patients with autism spectrum disorders (ASDs). STUDY
      DESIGN: Serum zonulin levels were determined in 32 patients with ASD and 33
      healthy controls using an enzyme-linked immunosorbent assay. The severity of ASD
      symptoms was assessed with the Childhood Autism Rating Scale. RESULTS: Serum
      zonulin levels were significantly higher in the patients with ASD (122.3 +/-
      98.46 ng/mL) compared with the healthy controls (41.89 +/- 45.83 ng/mL). There
      was a positive correlation between zonulin levels and Childhood Autism Rating
      Scale score when all subjects were assessed (r = 0.523; P < .001). CONCLUSIONS:
      This study suggests that zonulin, which regulates intestinal permeability, plays
      a role in the development of symptoms of ASD.

PMID- 28502608
TI  - The switch to infliximab biosimilars.

PMID- 28502610
TI  - Functional connectivity alterations in a murine model of optic neuritis.
AB  - The basis for neuronal dysfunction following inflammatory demyelination of the
      central nervous system (CNS) remains poorly understood. We characterized the
      network response to white matter injury in the anterior visual pathway using an
      experimental model of optic neuritis (ON), as ON is often an early manifestation
      of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical
      intrinsic signal imaging was performed before and after the induction of ON in
      mice to measure changes in cortical network functional connectivity. We observed
      a greater loss of connectivity between homotopic visual cortices in ON mice
      compared to controls. Further, decreases in homotopic visual cortex connectivity
      were associated with visual acuity loss in ON mice. These results demonstrate
      that network connectivity changes resulting from ON can be modeled in an
      experimental murine system. Future studies will identify the mechanisms that
      cause neuronal dysfunction due to white matter injury seen in MS.

PMID- 28502609
TI  - Switching from originator infliximab to biosimilar CT-P13 compared with
      maintained treatment with originator infliximab (NOR-SWITCH): a 52-week,
      randomised, double-blind, non-inferiority trial.
AB  - BACKGROUND: TNF inhibitors have improved treatment of Crohn's disease, ulcerative
      colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and
      chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was
      to examine switching from originator infliximab to the less expensive biosimilar
      CT-P13 regarding efficacy, safety, and immunogenicity. METHODS: The study is a
      randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow
      up. Adult patients on stable treatment with infliximab originator treated in a
      hospital setting for at least 6 months were eligible for participation. Patients
      with informed consent were randomised in a 1:1 ratio to either continued
      infliximab originator or to switch to CT-P13 treatment, with unchanged dosing
      regimen. Data were collected at infusion visits in 40 Norwegian study centres.
      Patients, assessors, and patient care providers were masked to treatment
      allocation. The primary endpoint was disease worsening during 52-week follow-up.
      394 patients in the primary per-protocol set were needed to show a non
      inferiority margin of 15%, assuming 30% disease worsening in each group. This
      trial is registered with ClinicalTrials.gov, number NCT02148640. FINDINGS:
      Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised
      (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from
      the full analysis and safety set for CT-P13) and 408 were included in the per
      protocol set (202 in the infliximab originator group and 206 in the CT-P13
      group). 155 (32%) patients in the full analysis set had Crohn's disease, 93 (19%)
      had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid
      arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque
      psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab
      originator group and 61 (30%) patients in the CT-P13 group (per-protocol set;
      adjusted treatment difference -4.4%, 95% CI -12.7 to 3.9). The frequency of
      adverse events was similar between groups (for serious adverse events, 24 [10%]
      for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168
      [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%]
      vs eight [3%], respectively). INTERPRETATION: The NOR-SWITCH trial showed that
      switching from infliximab originator to CT-P13 was not inferior to continued
      treatment with infliximab originator according to a prespecified non-inferiority
      margin of 15%. The study was not powered to show non-inferiority in individual
      diseases. FUNDING: Norwegian Ministry of Health and Care Services.

PMID- 28502614
TI  - Partially compromised specification causes stochastic effects on gut development
      in C. elegans.
AB  - The C. elegans gut descends from the E progenitor cell through a series of
      stereotyped cell divisions and morphogenetic events. Effects of perturbations of
      upstream cell specification on downstream organogenesis have not been extensively
      investigated. Here we have assembled an allelic series of strains that variably
      compromise specification of E by perturbing the activation of the gut-specifying
      end-1 and end-3 genes. Using a marker that allows identification of all E
      descendants regardless of fate, superimposed with markers that identify cells
      that have adopted a gut fate, we have examined the fate of E lineage descendants
      among hundreds of embryos. We find that when specification is partially
      compromised, the E lineage undergoes hyperplasia accompanied by stochastic and
      variable specification of gut fate among the E descendants. As anticipated by
      prior work, the activation of the gut differentiation factor elt-2 becomes
      delayed in these strains, although ultimate protein levels of a translational ELT
      2::GFP reporter resemble those of the wild type. By comparing these effects among
      the various specification mutants, we find that the stronger the defect in
      specification (i.e. the fewer number of embryos specifying gut), the stronger the
      defects in the E lineage and delay in activation of elt-2. Despite the changes in
      the E lineage in these strains, we find that supernumerary E descendants that
      adopt a gut fate are accommodated into a relatively normal-looking intestine.
      Hence, upstream perturbation of specification dramatically affects the E lineage,
      but as long as sufficient descendants adopt a gut fate, organogenesis overcomes
      these effects to form a relatively normal intestine.

PMID- 28502616
TI  - Bilateral antegrade cerebral perfusion during aortic dissection surgery: If no
      harm, then why not?

PMID- 28502615
TI  - Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.
AB  - Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord
      tissue after injury, generating new neurons that mature and integrate into the
      spinal circuitry. Elucidating the molecular signals that promote this
      regeneration is a fundamental question in regeneration research. Model systems,
      such as salamanders and larval and adult zebrafish are used to analyse successful
      regeneration. This shows that many developmental signals, such as Notch, Hedgehog
      (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF),
      Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and
      activate resident spinal progenitor cells. Here we compare the roles of these
      signals in spinal cord development and regeneration of the much larger and fully
      patterned adult spinal cord. Understanding how developmental signalling systems
      are reactivated in successfully regenerating species may ultimately lead to ways
      to reactivate similar systems in mammalian progenitor cells, which do not show
      neurogenesis after spinal injury.

PMID- 28502613
TI  - Unique patterns of organization and migration of FGF-expressing cells during
      Drosophila morphogenesis.
AB  - Fibroblast growth factors (FGF) are essential signaling proteins that regulate
      diverse cellular functions in developmental and metabolic processes. In
      Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and
      spatiotemporally restricted pattern to induce branching morphogenesis of the
      trachea, which expresses the Bnl-receptor, breathless (btl). Here we have
      developed a new strategy to determine bnl- expressing cells and study their
      interactions with the btl-expressing cells in the range of tissue patterning
      during Drosophila development. To enable targeted gene expression specifically in
      the bnl expressing cells, a new LexA based bnl enhancer trap line was generated
      using CRISPR/Cas9 based genome editing. Analyses of the spatiotemporal expression
      of the reporter in various embryonic stages, larval or adult tissues and in
      metabolic hypoxia, confirmed its target specificity and versatility. With this
      tool, new bnl expressing cells, their unique organization and functional
      interactions with the btl-expressing cells were uncovered in a larval
      tracheoblast niche in the leg imaginal discs, in larval photoreceptors of the
      developing retina, and in the embryonic central nervous system. The targeted
      expression system also facilitated live imaging of simultaneously labeled Bnl
      sources and tracheal cells, which revealed a unique morphogenetic movement of the
      embryonic bnl- source. Migration of bnl- expressing cells may create a dynamic
      spatiotemporal pattern of the signal source necessary for the directional growth
      of the tracheal branch. The genetic tool and the comprehensive profile of
      expression, organization, and activity of various types of bnl-expressing cells
      described in this study provided us with an important foundation for future
      research investigating the mechanisms underlying Bnl signaling in tissue
      morphogenesis.

PMID- 28502617
TI  - Topical amiodarone: To be or not to be effective?

PMID- 28502618
TI  - Training to be a thoracic surgeon: It's not idyllic, don't sugarcoat it, and
      don't stop learning!

PMID- 28502619
TI  - An apology or absolution for cerebral near-infrared spectroscopy: Can we get on
      the same wavelength?

PMID- 28502620
TI  - Discussion.

PMID- 28502621
TI  - Protein-based prognostic biomarkers in lung cancer: Promise or pitfall?

PMID- 28502622
TI  - How Andre Agassi helped me during my cardiothoracic surgery training.

PMID- 28502611
TI  - Defining the momiome: Promiscuous information transfer by mobile mitochondria and
      the mitochondrial genome.
AB  - Mitochondria are complex intracellular organelles that have long been identified
      as the powerhouses of eukaryotic cells because of the central role they play in
      oxidative metabolism. A resurgence of interest in the study of mitochondria
      during the past decade has revealed that mitochondria also play key roles in cell
      signaling, proliferation, cell metabolism and cell death, and that genetic and/or
      metabolic alterations in mitochondria contribute to a number of diseases,
      including cancer. Mitochondria have been identified as signaling organelles,
      capable of mediating bidirectional intracellular information transfer:
      anterograde (from nucleus to mitochondria) and retrograde (from mitochondria to
      nucleus). More recently, evidence is now building that the role of mitochondria
      extends to intercellular communication as well, and that the mitochondrial genome
      (mtDNA) and even whole mitochondria are indeed mobile and can mediate information
      transfer between cells. We define this promiscuous information transfer function
      of mitochondria and mtDNA as "momiome" to include all mobile functions of
      mitochondria and the mitochondrial genome. Herein, we review the "momiome" and
      explore its role in cancer development, progression, and treatment.

PMID- 28502623
TI  - Documentation of vital status in the United States of America.

PMID- 28502612
TI  - MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate
      Functional Annotation of the Human Genome.
AB  - One major challenge encountered with interpreting human genetic variants is the
      limited understanding of the functional impact of genetic alterations on
      biological processes. Furthermore, there remains an unmet demand for an efficient
      survey of the wealth of information on human homologs in model organisms across
      numerous databases. To efficiently assess the large volume of publically
      available information, it is important to provide a concise summary of the most
      relevant information in a rapid user-friendly format. To this end, we created
      MARRVEL (model organism aggregated resources for rare variant exploration).
      MARRVEL is a publicly available website that integrates information from six
      human genetic databases and seven model organism databases. For any given variant
      or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and
      DECIPHER. Importantly, it curates model organism-specific databases to
      concurrently display a concise summary regarding the human gene homologs in
      budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage.
      Experiment-based information on tissue expression, protein subcellular
      localization, biological process, and molecular function for the human gene and
      homologs in the seven model organisms are arranged into a concise output. Hence,
      rather than visiting multiple separate databases for variant and gene analysis,
      users can obtain important information by searching once through MARRVEL.
      Altogether, MARRVEL dramatically improves efficiency and accessibility to data
      collection and facilitates analysis of human genes and variants by cross
      disciplinary integration of 18 million records available in public databases to
      facilitate clinical diagnosis and basic research.

PMID- 28502624
TI  - Prospective study of giant paraesophageal hernia repair with 1-year follow-up.
AB  - OBJECTIVE: Evaluating giant paraesophageal hernia (GPEH) repair requires long
      term follow-up. GPEH repair can have associated high recurrence rates, yet this
      incidence depends on how recurrence is defined. Our objective was to
      prospectively evaluate patients undergoing GPEH repair with 1-year follow-up.
      METHODS: Patients undergoing elective GPEH repair between 2011 and 2014 were
      enrolled prospectively. Postoperatively, patients were evaluated at 1 month and 1
      year. Radiographic recurrence was evaluated by barium swallow and defined as a
      gastroesophageal junction located above the hiatus. Quality of life was evaluated
      pre- and postoperatively with the use of a validated questionnaire. RESULTS: One
      hundred six patients were enrolled. The majority of GPEH repairs were performed
      laparoscopically (80.2%), and 7.5% were redo repairs. At 1-year follow-up, 63.4%
      of patients were symptom free, and radiographic recurrence was 32.7%. Recurrence
      rate was 18.8% with standard definition (>2 cm of stomach above the diaphragm).
      Quality of life scores at 1 year were significantly better after operative
      repair, even in patients with radiographic recurrence (7.0 vs 22.5 all patients,
      13.0 vs 22.5 with recurrence; P < .001). Patients with small radiographic
      recurrences have similar satisfaction and symptom severity to patients with >2 cm
      recurrences. CONCLUSIONS: GPEH repair can be performed with low operative
      mortality and morbidity. The rate of recurrence at 1 year depends on the
      definition used. Patient satisfaction and symptom severity are similar between
      patients with radiographic and greater than 2 cm hernia recurrences. Longer
      follow-up and critical assessment of our results are needed to understand the
      true impact of this procedure and better inform perioperative decision making.

PMID- 28502626
TI  - Organic matter in surface sediments from the Gulf of Mexico and South China Sea:
      Compositions, distributions and sources.
AB  - Sediments from the Gulf of Mexico (GOM) and the South China Sea (SCS) were
      analyzed. The low delta13 C values of pentamethylicosane (PMIs) and fatty acids (
      81.3 to -85.20/00) were found in only the S-1 sample collected from the GOM,
      indicating that methanogenic archaea associated with gas hydrate formation
      contributed to the sediment organic matter. Principle component analysis of fatty
      acids suggested that similar microbial biomass was found in the S-1, S-9, O-3 and
      O-5 samples. However, a comparison of the alkanes, fatty acids, and alcohols
      indicated that the percentage of n-alkan-2-ols in the S-1 sample from the GOM was
      the highest, while n-alkanes and n-fatty acids were the highest percentages in
      other samples from the GOM and SCS. This finding suggests that microbial species
      or the oxidation/reduction environment of the sample site of S-1 were different
      from those of the other samples. The present study provides a basis for detecting
      gas hydrate sites on the seafloor of the SCS.

PMID- 28502627
TI  - Distribution of PBDEs, HBCDs and PCBs in the Brisbane River estuary sediment.
AB  - To date, very little or no data exist in literature for some brominated flame
      retardants (BFRs) and polychlorinated biphenyls in Queensland sediments. These
      pollutants were measured in the sediments along the Brisbane River estuary. The
      target compounds were regularly detected in measurable concentrations: PBDEs=33.3
      97.8% (n=45), PCBs=94.1-100% (n=51) and HBCDs=79-98% (n=48). Consistently, >90%
      of the observed ?8PBDE concentration was attributed to BDE-209. Mean PBDE levels
      (ng/g dry wt.) were: 4.4+/-3.2 (?8PBDE) and 4.4+/-3.0 (BDE-209) across 22
      sampling sites. The mean ?7PCB and ?HBCD were 5.4+/-4.5 and 1.0+/-1.5ng/g dry wt.
      respectively. The 25% (alpha-HBCD), 8% (beta-HBCD) and 67% (gamma-HBCD)
      diastereoisomer contributions observed were consistent with values reported in
      the literature. Contaminant levels are fairly distributed along the River and
      were generally low compared to similar studies around the world.

PMID- 28502628
TI  - Magnetic fibrous sorbent for remote and efficient oil adsorption.
AB  - Oil spill accident and oily water have potential risks to environment and human
      health, thus need to be imperatively treated. Herein, a magnetic fibrous sorbent
      was designed via electrospinning of suspension containing polymer and magnetic
      nanoparticles in one step for remote and efficient oil adsorption. The morphology
      of the magnetic fibrous sorbent was characterized by scanning electron
      microscopy. The magnetic property and the wetting behavior were measured by
      vibrating sample magnetometer and contact angle system, respectively. The results
      showed that the morphology of the fibers was homogeneous and the magnetic
      nanoparticles were well dispersed within the fibers. It was also found that this
      composite sorbent had good magnetic response, special wettability, and remote oil
      adsorption capacity. We believed this novel polymer/Fe3O4 fibrous sorbent could
      be used as a promising material for the remote oil/water separation.

PMID- 28502629
TI  - The inhibitory effects of levo-tetrahydropalmatine on rat Kv1.5 channels
      expressed in HEK293 cells.
AB  - Levo-tetrahydropalmatine (l-THP) exerts various pharmacological effects on neural
      and cardiac tissues and K+ channel can be one of its multiple targets. The
      rapidly activating Kv1.5 channel is expressed in a variety of tissues including
      atrial cells and hippocampal neurons, and has an essential role in tuning the
      action potential and excitability in those cells. The aim of current study is to
      explore whether there are the possible effects of l-THP on Kv1.5 channels
      expressed in HEK293 cells. Superfusion of l-THP led to a dose-dependent blockage
      of Kv1.5 currents with an IC50 value of 53.2MUM. This blocking effect was
      substantially attenuated in mutant H452G rather than R476V and R476Y, suggesting
      a specific binding site in the outer mouth region. In addition, the properties of
      Kv1.5 channel kinetics were markedly altered by l-THP. Treatment with l-THP
      resulted in a potential left shift of the inactivation curve, with the half
      maximum inactivation potential (V1/2) of 4.5mV in control and -12.8mV in 50MUM l
      THP. Our data reveal that l-THP can exert an inhibitory effect on the delayed
      rectifier Kv1.5 channels expressed in HEK293 cells. These lines of evidence
      provided an insight to understand the possible effects exerted by l-THP on
      relative tissues.

PMID- 28502630
TI  - New opioid receptor antagonist: Naltrexone-14-O-sulfate synthesis and
      pharmacology.
AB  - Opioid antagonists, naloxone and naltrexone have long been used in clinical
      practice and research. In addition to their low selectivity, they easily pass
      through the blood-brain barrier. Quaternization of the amine group in these
      molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In
      addition, zwitterionic compounds have been reported to have limited CNS access.
      The current study, for the first time gives report on the synthesis and the in
      vitro [competition binding, G-protein activation, isolated mouse vas deferens
      (MVD) and mouse colon assay] pharmacology of the zwitterionic compound,
      naltrexone-14-O-sulfate. Naltrexone, naloxone, and its 14-O-sulfate analogue were
      used as reference compounds. In competition binding assays, naltrexone-14-O
      sulfate showed lower affinity for u, delta or kappa opioid receptor than the
      parent molecule, naltrexone. However, the MU/kappa opioid receptor selectivity
      ratio significantly improved, indicating better selectivity. Similar tendency was
      observed for naloxone-14-O-sulfate when compared to naloxone. Naltrexone-14-O
      sulfate failed to activate [35S]GTPgammaS-binding but inhibit the activation
      evoked by opioid agonists (DAMGO, Ile5,6deltorphin II and U69593), similarly to
      the reference compounds. Schild plot constructed in MVD revealed that naltrexone
      14-O-sulfate acts as a competitive antagonist. In mouse colon, naltrexone-14-O
      sulfate antagonized the inhibitory effect of morphine with lower affinity
      compared to naltrexone and higher affinity when compared to naloxone or naloxone
      14-O-sulfate. In vivo (mouse tail-flick test), subcutaneously injected naltrexone
      14-O-sulfate antagonized morphine's antinociception in a dose-dependent manner,
      indicating it's CNS penetration, which was unexpected from such zwitter ionic
      structure. Future studies are needed to evaluate it's pharmacokinetic profile.

PMID- 28502631
TI  - A brain-targeted ampakine compound protects against opioid-induced respiratory
      depression.
AB  - The use of opioid drugs for pain relief can induce life-threatening respiratory
      depression. Although naloxone effectively counteracts opioid-induced respiratory
      depression, it diminishes the efficacy of analgesia. Our studies indicate that
      ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse
      respiratory depression without affecting analgesia at relatively low doses. Mice
      and rats were subcutaneously or intravenously injected with the opioid agonist TH
      030418 to induce moderate or severe respiratory depression. XD-8-17C was
      intravenously administered before or after TH-030418. The effect of XD-8-17C on
      opioid-induced respiratory depression was evaluated in terms of the opioid
      induced acute death rate, arterial blood gas analysis and pulmonary function
      tests. In addition, the hot-plate test was conducted to investigate whether XD-8
      17C influenced opioid-induced analgesia. Pre-treatment with XD-8-17C
      significantly reduced opioid-induced acute death, and increased the median lethal
      dose of TH-030418 by 4.7-fold. Blood gas analysis and pulmonary function tests
      demonstrated that post-treatment with XD-8-17C alleviated respiratory depression,
      as indicated by restoration of arterial blood gas (pO2, sO2, cK+) and lung
      function parameters (respiratory frequency, minute ventilation) to the normal
      range. The hot-plate test showed that XD-8-17C had no impact on the
      antinociceptive efficacy of morphine. The ability of XD-8-17C to reverse opioid
      induced respiratory depression has the potential to increase the safety and
      convenience of opioid treatment. These findings contribute to the discovery of
      novel therapeutic agents that protect against opioid-induced respiratory
      depression without loss of analgesia.

PMID- 28502633
TI  - Remapping nociceptive stimuli into a peripersonal reference frame is spatially
      locked to the stimulated limb.
AB  - The localization of harmful stimuli approaching our body is essential for
      survival. Here we investigated whether the mapping of nociceptive stimuli is
      based on a spatial representation that is anchored to the stimulated limb. In
      three experiments, we measured the effect of unilateral visual stimuli on the
      perceived temporal order of nociceptive stimuli, applied to each hand. Crucially,
      the position of the hands and the visual stimuli was manipulated, so that visual
      and nociceptive stimuli occurred in an adjacent or non-adjacent spatial position.
      Temporal order judgments of nociceptive stimuli were biased in favor of the
      stimulus applied to the hand most adjacent to the visual stimulus, irrespective
      to their positions in space. This suggests that the ability to determine the
      position of a nociceptive stimulus on a specific body area is based on a
      peripersonal representation of the stimulated limb following it during limb
      displacement.

PMID- 28502634
TI  - At Home in America: One Foreign Medical Graduate's View.

PMID- 28502632
TI  - Two years later - Revisiting autobiographical memory representations in vmPFC and
      hippocampus.
AB  - A long-standing question in memory neuroscience concerns how and where
      autobiographical memories of personal experiences are represented in the brain.
      In a previous high resolution multivoxel pattern analysis fMRI study, we examined
      two week old (recent) and ten year old (remote) autobiographical memories
      (Bonnici et al., 2012, J. Neurosci. 32:16982-16991). We found that remote
      memories were particularly well represented in ventromedial prefrontal cortex
      (vmPFC) compared to recent memories. Moreover, while both types of memory were
      represented within anterior and posterior hippocampus, remote memories were more
      easily distinguished in the posterior portion. These findings suggested that a
      change of some kind had occurred between two weeks and ten years in terms of
      where autobiographical memories were represented in the brain. In order to
      examine this further, here participants from the original study returned two
      years later and recalled the memories again. We found that there was no
      difference in the detectability of memory representations within vmPFC for the
      now 2 year old and 12 year old memories, and this was also the case for the
      posterior hippocampus. Direct comparison of the two week old memories (original
      study) with themselves two years later (present study) confirmed that their
      representation within vmPFC had become more evident. Overall, this within
      subjects longitudinal fMRI study extends our understanding of autobiographical
      memory representations by allowing us to narrow the window within which their
      consolidation is likely to occur. We conclude that after a memory is initially
      encoded, its representation within vmPFC has stablised by, at most, two years
      later.

PMID- 28502635
TI  - Identification of vitreous proteins in retinopathy of prematurity.
AB  - Retinopathy of prematurity (ROP) is a disorder of blood vessels in the retina
      developed in premature infants and the leading cause of the blindness in
      children. Proteomic analysis was performed to identify vitreous proteins specific
      to patients with ROP. Vitreous humor samples were obtained from three patients
      with ROP and two patients with congenital cataract, the latter included as a
      control group. The vitreous samples were separated by 2D-PAGE and the proteins
      running as definitive spots were identified by MALDI-TOF MS spectrometry. We
      identified 13 and 6 proteins in the vitreous from ROP and cataract patients,
      respectively. Albumin, transferrin, pigment epithelium-derived factor (PEDF) and
      transthyretin were found in both patient groups. In the samples from ROP
      patients, PEDF and transthyretin levels were lower than in those from cataract
      patients, and retinol binding protein 3 and prostaglandin D synthase were not
      detected. Of the 13 proteins, 9 proteins including alpha-2-macroglobulin,
      ceruloplasmin, alpha-fetoprotein, vitamin D-binding protein, alpha-1-antitrypsin,
      alpha-1-beta-glycoprotein, hemopexin, apolipoprotein A-1 and A-lV were found in
      vitreous samples of only the ROP patients. PEDF has anti-angiogenic and
      neurotrophic functions. Whether PEDF is increased or decreased in diabetic
      retinopathy has been controversial but we observed lower PEDF in the ROP samples
      than in the controls. The proteins specific to or decreased in ROP, if confirmed
      in future studies, may provide clue to understanding its pathogenesis.

PMID- 28502636
TI  - Diabetogenic agent alloxan is a proteasome inhibitor.
AB  - Alloxan has been used as a diabetogenic agent to induce diabetes. It selectively
      induces pancreatic beta-cell death. The specific toxicity, however, is not fully
      understood. In this study, we observed the effect of alloxan on proteasome
      function. We found that alloxan caused the accumulation of ubiquitinated proteins
      in NRK cells through the inhibition of the proteolytic activities of the
      proteasome. Biochemistry experiments with purified 26S and 20S proteasomes
      revealed that alloxan directly acts on the chymotrypsin- and trypsin-like
      peptidase activities. These results demonstrate that alloxan is a proteasome
      inhibitor, which suggests that its specific toxicity toward beta-cell is at least
      in part through proteasome inhibition.

PMID- 28502638
TI  - Oncology nurses' knowledge of guidelines for preventing catheter-related
      bloodstream infections.
AB  - This descriptive cross-sectional survey evaluated Jordanian oncology nurses'
      knowledge of the guidelines for preventing central venous catheter-associated
      infection. Poor knowledge was evident from the very low mean total scores and the
      low percentage of correct answers for each item in the questionnaire.

PMID- 28502637
TI  - Bathing hospitalized dependent patients with prepackaged disposable washcloths
      instead of traditional bath basins: A case-crossover study.
AB  - BACKGROUND: Basins used for patient bathing have been shown to be contaminated
      with multidrug-resistant organisms (MDROs) and have prompted the evaluation of
      alternatives to soap and water bathing methods. METHODS: We conducted a
      prospective, randomized, open-label interventional crossover study to assess the
      impact of replacing traditional bath basins with prepackaged washcloths on the
      incidence of hospital-associated infections (HAIs), MDROs, and secondarily, rates
      of skin deterioration. Unit-wide use of disposable washcloths over an 8-month
      period was compared with an 8-month period of standard care using basins.
      RESULTS: A total of 2,637 patients were included from 2 medical-surgical units at
      a single tertiary medical center, contributing 16,034 patient days. During the
      study period, there were a total of 33 unit-acquired infections, the rates of
      which were not statistically different between study phases (incidence rate
      ratio, 1.05; 95% confidence interval [CI], 0.50-2.23; P = .88). However,
      occurrence of skin integrity deterioration was significantly less in the
      intervention group (odds ratio, 0.44; 95% CI, 0.22-0.88; P = .02). CONCLUSIONS:
      Although we were unable to demonstrate a significant reduction in HAI or MDRO
      acquisition, we found a decrease in skin deterioration with the use of disposable
      washcloths and confirmed earlier findings of MDRO contamination of wash basins.

PMID- 28502639
TI  - Too much Ophthalmology? Ophthalmology in the era of over-diagnosis and over
      treatment.

PMID- 28502640
TI  - A cohort study reveals myocarditis to be a rare and life-threatening presentation
      of large vessel vasculitis.
AB  - BACKGROUND: The predominant forms of adult large vessel vasculitis (LVV) are
      giant cell arteritis (GCA) and Takayasu arteritis (TA). Cardiac involvement in
      LVV is a cause of morbidity and mortality, particularly in TA. Cardiac failure is
      most commonly secondary to uncontrolled arterial hypertension or myocardial
      ischaemia. Pulmonary hypertension and aortic valve incompetence following
      ascending aortic dilatation represent other serious cardiovascular complications.
      However, cardiac failure as a consequence of myocarditis is rarely reported,
      principally in single case reports or in autopsy studies. METHODS: The Imperial
      College LVV database was, retrospectively, reviewed to identify patients with
      cardiac involvement at presentation. Patients with evidence for myocarditis were
      identified. The cardiac presentation, imaging studies and subsequent medical and
      surgical management were reviewed in detail. RESULTS: The cohort included 139
      patients with TA and 24 with GCA. Sixteen presented with cardiac failure without
      a history of ischaemic coronary heart disease, 14 (10%) with TA and 2 (8.3%) with
      GCA. Cardiovascular disease identified at presentation included aortic
      regurgitation (n = 11), myocarditis (n = 4) and hypertensive cardiomyopathy
      secondary to renal artery stenosis (n = 1). Those patients with evidence of
      myocarditis at presentation (2.8%) underwent transthoracic echocardiography and
      cardiac magnetic resonance imaging (CMR). These non-invasive techniques were
      sufficient for diagnosis of clinically significant myocarditis. Furthermore, they
      were subsequently used to monitor response to treatment, with serial improvement
      in left ventricular ejection fraction (LVEF) observed in all 4 patients (p <
      0.05). Prednisolone plus cyclophosphamide (CyC) therapy was associated with
      significant improvement in heart failure symptoms and LVEF in 3 cases. In one
      case where CyC was contraindicated, tocilizumab treatment led to marked
      improvement in cardiac symptoms. CONCLUSION: Clinically significant myocarditis
      in LVV remains a rare but serious presentation. Non-invasive imaging techniques
      offer an alternative to the gold-standard myocardial biopsy. Initial aggressive
      immunosuppressive therapy is recommended and led to significant improvements in
      LVEF and cardiac status.

PMID- 28502641
TI  - Insights in luteovirid structural biology guided by chemical cross-linking and
      high resolution mass spectrometry.
AB  - Interactions among plant pathogenic viruses in the family Luteoviridae and their
      plant hosts and insect vectors are governed by the topology of the viral capsid,
      which is the sole vehicle for long distance movement of the viral genome.
      Previous application of a mass spectrometry-compatible cross-linker to
      preparations of the luteovirid Potato leafroll virus (PLRV; Luteoviridae:
      Polerovirus) revealed a detailed network of interactions between viral structural
      proteins and enabled generation of the first cross-linking guided coat protein
      models. In this study, we extended application of chemical cross-linking
      technology to the related Turnip yellows virus (TuYV; Luteoviridae: Polerovirus).
      Remarkably, all cross-links found between sites in the viral coat protein found
      for TuYV were also found in PLRV. Guided by these data, we present two models for
      the TuYV coat protein trimer, the basic structural unit of luteovirid virions.
      Additional cross-links found between the TuYV coat protein and a site in the
      viral protease domain suggest a possible role for the luteovirid protease in
      regulating the structural biology of these viruses.

PMID- 28502642
TI  - Molecular detection of tick-borne pathogens in wild red foxes (Vulpes vulpes)
      from Central Italy.
AB  - Spleen samples from 153 red foxes, shot during regular hunting season in the
      province of Pisa (Central Italy), were examined to detect DNA of Anaplasma
      phagocytophilum, Ehrlichia canis, Coxiella burnetii, Francisella tularensis,
      Hepatozoon canis and Babesia sp./Theileria sp. DNA of vector-borne pathogens was
      detected in 120 (78.43%; 95% CI: 71.06-84.66%) foxes. Specifically, 75 (49%; 95%
      CI: 40.86-57.22%) animals scored PCR-positive per H. canis, 68 (44.44%; 95% CI:
      36.42-52.69%) for E. canis, 35 (22.88%; 95% CI: 16.48-30.35%) for piroplasms
      (Theileria annae), 3 (1.96%; 95% CI: 0.41-5.62%) for C. burnetii and 1 (0.65%;
      95% CI: 0.02-3.59%) for A. phagocytophilum. No positive reaction was observed for
      F. tularensis. Fifty-six animals (36.6%; 95% CI: 28.97-44.76%) were positive for
      two or three pathogens. Red foxes result to be involved in the cycle of vector
      borne pathogens that are associated to disease in dogs and humans.

PMID- 28502645
TI  - Elderly patients in a Mexican intensive care unit: A retrospective analysis.

PMID- 28502644
TI  - Leishmania (V.) braziliensis infecting bats from Pantanal wetland, Brazil: First
      records for Platyrrhinus lineatus and Artibeus planirostris.
AB  - In the New World genus Leishmania parasites are etiological agents of neglected
      zoonoses known as leishmaniasis. Its epidemiology is very complex due to the
      participation of several species of sand fly vectors and mammalian hosts, and man
      is an accidental host. Control is very difficult because of the different
      epidemiological patterns of transmission observed. Studies about Leishmania spp.
      infection in bats are so scarce, which represents a large gap in knowledge about
      the role of these animals in the transmission cycle of these pathogens,
      especially when considering that Chiroptera is one of the most abundant and
      diverse orders among mammals. Leishmaniasis in Mato Grosso do Sul, Brazil are
      remarkably frequent, probably due to the abundance of its regional mastofauna.
      The recent record of L. braziliensis in bats from this state indicates the need
      to clarify the role of these mammals in the transmission cycle. In this study we
      evaluated the presence of Leishmania parasites in the skin of different species
      of bats, using PCR directed to Leishmania spp. kDNA for screening followed by
      PCR/RFLP analysis of the hsp70 gene for the identification of parasite species.
      Leishmania species identification was confirmed by PCR directed to the G6PD gene
      of L. braziliensis, followed by sequencing of the PCR product. Samples from 47
      bats were processed, of which in three specimens (6.38%) was detected the
      presence of Leishmania sp. kDNA. PCR/RFLP and sequencing identified the species
      involved in the infection as L. braziliensis in all of them. This is the first
      report of Leishmania braziliensis in bats from Pantanal ecosystem and the first
      record of this species in Platyrrhinus lineatus and Artibeus planirostris, bats
      with a wide distribution in South America. These results reinforce the need to
      deepen the knowledge about the possibility of bats act as reservoirs of
      Leishmania spp. especially considering their ability of dispersion and occupation
      of anthropic environments.

PMID- 28502646
TI  - Trigger reverse identification in critical care setting.

PMID- 28502643
TI  - Are brucellosis, Q fever and melioidosis potential causes of febrile illness in
      Madagascar?
AB  - Brucellosis, Q fever and melioidosis are zoonoses, which can lead to pyrexia.
      These diseases are often under-ascertained and underreported because of their
      unspecific clinical signs and symptoms, insufficient awareness by physicians and
      public health officers and limited diagnostic capabilities, especially in low
      resource countries. Therefore, the presence of Brucella spp., Coxiella burnetii
      and Burkholderia pseudomallei was investigated in Malagasy patients exhibiting
      febrile illness. In addition, we analyzed zebu cattle and their ticks as
      potential reservoirs for Brucella and C. burnetii, respectively. Specific
      quantitative real-time PCR assays (qPCRs) were performed on 1020 blood samples
      drawn from febrile patients. In total, 15 samples (1.5%) were Brucella-positive,
      mainly originating from patients without travel history, while DNA from C.
      burnetii and Bu. pseudomallei was not detected. Anti-C. burnetii antibodies were
      found in four out of 201 zebu serum samples (2%), whereas anti-Brucella
      antibodies could not be detected. Brucella DNA was detected in a single zebu
      sample. Three out of 330 ticks analyzed (1%) were positively tested for C.
      burnetii DNA but with high Ct values in the qPCR assay. Our data suggest that
      zebus as well as Amblyomma and Boophilus ticks have to be considered as a natural
      reservoir or vector for C. burnetii, but the risk of cattle-to-human transmission
      is low. Since bovine brucellosis does not seem to contribute to human infections
      in Madagascar, other transmission routes have to be assumed.

PMID- 28502647
TI  - An accurate, specific, sensitive, high-throughput method based on a microsphere
      immunoassay for multiplex detection of three viruses and bacterial fruit blotch
      bacterium in cucurbits.
AB  - To employ a microsphere immunoassay (MIA) to simultaneously detect multiple plant
      pathogens (potyviruses, Watermelon silver mottle virus, Melon yellow spot virus,
      and Acidovorax avenae subsp. citrulli) in actual plant samples, several factors
      need to be optimized and rigorously validated. Here, a simple extraction method
      using a single extraction buffer was successfully selected to detect the four
      pathogens in various cucurbit samples (cucumber, cantaloupe, melon, and
      watermelon). The extraction method and assay performance were validated with
      inoculated and field cucurbit samples. The MIA showed 98-99% relative accuracy,
      97-100% relative specificity and 92-100% relative sensitivity when compared to
      commercial ELISA kits and reverse transcription PCR. In addition, the MIA was
      also able to accurately detect multiple-infected field samples. The results
      demonstrate that one common extraction method for all tested cucurbit samples
      could be applied to detect multiple pathogens; avoiding the need for multiple
      protocols to be employed. This multiplex method can therefore be instrumental for
      high-throughput screening of multiple plant pathogens with many advantages such
      as a shorter assay time (2.5h) with single assay format, a lower cost of
      detection ($5 vs $19.7 for 4 pathogens/sample) and less labor requirement. Its
      multiplex capacity can also be expanded to detect up to 50 different pathogens
      upon the availability of specific antibodies.

PMID- 28502648
TI  - Control of astrocyte morphology by Rho GTPases.
AB  - Astrocytes modulate and support neuronal and synapse function via numerous
      mechanisms that often rely on diffusion of signalling molecules, ions or
      metabolites through extracellular space. As a consequence, the spatial
      arrangement and the distance between astrocyte processes and neuronal structures
      are of functional importance. Likewise, changes of astrocyte structure will
      affect the ability of astrocytes to interact with neurons. In contrast to
      neurons, where rapid morphology changes are critically involved in many aspects
      of physiological brain function, a role of astrocyte restructuring in brain
      physiology is only beginning to emerge. In neurons, small GTPases of the Rho
      family are powerful initiators and modulators of structural changes. Less is
      known about the functional significance of these signalling molecules in
      astrocytes. Here, we review recent experimental evidence for the role of RhoA,
      Cdc42 and Rac1 in controlling dynamic astrocyte morphology as well as
      experimental tools and analytical approaches for studying astrocyte morphology
      changes.

PMID- 28502649
TI  - Post-implantation development of red-rumped agouti (Dasyprocta leporina Linnaeus,
      1758).
AB  - Fourteen pregnant agouti (Dasyprocta leporina Linnaeus, 1758) females at
      gestational ages of 30-100days and two at gestational ages of 55-100days, were
      studied, including 24 embryos/fetuses and two neonates (single offspring from two
      females). Females were euthanized and embryos/fetuses were examined, measured,
      and photographed. Embryos at 30days post-copulation were "C-shaped," with paddle
      shaped limb buds and 10.75+/-0.11mm crown-rump length (CRL). In embryos at 35days
      post-copulation, paddle-shaped forelimbs, fin-shaped pelvic limbs, and a liver
      bud were evident, with 15.6+/-0.16mm CRL; at 45days, mouth and nostrils were
      evident, lower incisors were emerging, and tactile hairs could be seen near the
      nostrils, with 40.8+/-0.4mm CRL; at 55days, cranial sutures had fused, digits
      were totally separated and claws formation was beginning, with 58.8+/-0.1mm CRL;
      at 65days, the genital bud had differentiated, with 83+/-0.08mm CRL; at 85days,
      the body was covered with short hair, with 127.7+/-0.6mm CRL; and at 100days, the
      mature fetus had fully formed teeth and claws and an open external acoustic
      meatus, with 164.3+/-10.4mm CRL. Neonates had bristly hair and open eyes, with
      179.1+/-0.5mm CRL. In conclusion, characteristics of the embryo/fetus during
      pregnancy can be used to estimate gestational age, and can be used as parameters
      during ultrasound examinations to help identify developmental pathologies and to
      test effects of nutrition, drugs, and pollution on pregnancy.

PMID- 28502650
TI  - Crayfish immunity - Recent findings.
AB  - Freshwater crayfish is an important commodity as well as a successful model for
      studies on crustacean immunity. Due to the ease with which they are kept and the
      available methods for hemocyte separation and culture they have proven to be very
      useful. Here, recent progress regarding pattern recognition, immune effector
      production and antiviral mechanisms are discussed. Several cases of functional
      resemblance between vertebrate complement and the crayfish immune reactions are
      highlighted.

PMID- 28502651
TI  - RACK-1, a multifaceted regulator is required for C. elegans innate immunity
      against S. flexneri M9OT infection.
AB  - The nematode C. elegans has the ability to clear off bacterial colonization in
      the intestine using pathogen specific innate immune response. Here, we show that
      C. elegans RACK-1 has been vital in determining the survival of worms under
      specific pathogenic infection. Among various pathogens tested, S. flexneri M9OT
      (SF) exhibited highest pathogenicity by killing rack-1 mutant worm-VC3013 earlier
      when compared to WT. The expression level of rack-1 mRNA was found to be
      decreased and it further indicated that the host translational event appeared to
      be affected during SF infection. Hence, inhibition of translational machinery was
      the foremost reason for the early mortality in C. elegans. Apparently, variation
      in the expression of RACK-1 affects the activation of p38 and JNK-MAPK pathway
      which consequently triggered expression of nlp-29 and longevity, respectively.
      The study unveils novel defense mechanisms exist for C. elegans in facilitating
      enhanced immunity by RACK-1 against SF infection.

PMID- 28502652
TI  - Comparative and evolutionary analysis of an adapter molecule MyD88 in
      invertebrate metazoans.
AB  - The myeloid differentiation factor 88 (MyD88) is an essential adapter in Toll
      like receptor (TLR) signalling pathways, with TLR the first pattern-recognition
      receptor (PRR) that was discovered in Drosophila. In the present study, a MyD88
      gene was identified and characterized from a commercially important shellfish,
      Scapharca subcrenata, including a DEATH domain and TIR domain conserved within
      other molluscs. Furthermore, comparative genomic evidence revealed that MyD88 was
      of different lengths and contained quantitative exon and intron regions, which
      might be involved in specific mechanisms. To further explore the phylogenetic
      relationships of invertebrate metazoan MyD88, we applied MrBayes and PhyML
      software to construct phylogenetic trees using Bayesian and maximum likelihood
      approaches, respectively, which suggested that the MyD88 of Arthropoda was
      closely related to lower invertebrates, in contrast to morphological taxonomy.
      Finally, we investigated the evolutionary patterns and location of positive
      selection sites (PSSs) in the MyD88 gene from Arthropoda, Mollusca and Insecta
      using PAML software with the maximum likelihood method. The data showed that
      positive selection sites were detected in these groups, and partial sites were
      located in the TIR domain but were not found in the DEATH domain. To summarize,
      in this study, we report on the diversification of MyD88 in invertebrate
      metazoans, the specific evolutionary position of Arthropoda MyD88, and the
      positive selection pressures on MyD88 of Arthropoda, Mollusca and Insecta. These
      results are a valuable contribution to understand and clarify the evolutionary
      pattern of TLR/MyD88 signalling pathways in invertebrate and vertebrate taxa.

PMID- 28502653
TI  - Heart-sparing radiotherapy in patients with breast cancer: What are the
      techniques used in the clinical routine?: A pattern of practice survey in the
      German-speaking countries.
AB  - The aim of this study was to understand the practice of care in German-speaking
      countries with regard to heart-sparing radiotherapy techniques. Between August
      2015 and September 2015, an e-mail/fax-based survey was sent to radiation
      oncology departments in Germany, Austria, and the German-speaking Switzerland.
      The questionnaire was divided into 3 chapters: a general chapter on the
      department, a chapter specific for heart-sparing techniques in patients with
      breast cancer, and a third chapter on personal beliefs on the topic of heart
      sparing in patients with breast cancer. A total of 82 radiation oncology
      departments answered the questionnaire: 16 university clinics and 66 other
      departments. In general, heart-sparing techniques are being offered by 90.2% of
      departments for radiation oncology in the German-speaking countries. However, in
      the clinical routine, 87.7% of institutions use heart-sparing techniques in less
      than 50% of patients with breast cancer. Heart-sparing techniques are especially
      provided for patients with left-sided breast cancer (80%), patients after
      mastectomy (52.5%), and when the mammaria interna lymph drainage vessels are
      irradiated (41.3%). In 46.3% of departments, there are written internal
      guidelines for heart sparing in patients with breast cancer. Breathing-adapted
      radiotherapy is used as the most frequent heart-sparing technique in 64.7% of the
      institutions, followed by intensity-modulated radiation therapy, which is most
      frequently used by 22.1%. The only significant difference between university
      hospitals and other departments was seen for the offering of partial breast
      irradiation. The most commonly used heart-sparing technique is breathing-adapted
      radiotherapy, but there is no coherent approach for heart sparing in patients
      with breast cancer in the German-speaking countries. Overall, all options for
      cardiac protection/cardiac avoidance have their advantages and disadvantages,
      with deep inspiration breath-hold radiotherapyhaving the most clear data, which
      should be the preferred choice when using heart-sparing techniques.

PMID- 28502654
TI  - Radiation-induced hypothyroidism in patients with breast cancer: a retrospective
      analysis of 243 cases.
AB  - This study aims to estimate the incidence of hypothyroidism (HT) and to evaluate
      the predictors affecting the development of HT after radiotherapy (RT) for breast
      cancer, with a focus on radiation dose-volumetric parameters. Between 2009 and
      2015, 243 patients undergoing RT for breast cancer were retrospectively analyzed.
      Free triiodothyronine (FT3), free thyroxin (FT4), and thyrotropin (TSH) were
      monitored before and after RT. The relation between the doses to thyroid gland
      (Dmean, Dmax, Dmin), percentage of thyroid volume receiving > 10 Gy, 20 Gy, 30
      Gy, 40 Gy, and 50 Gy (V10 to V50), absolute thyroid volume, and HT were analyzed.
      The risk of HT according to radiation fields and the other clinic factors were
      also evaluated. The median follow-up was 41 (range; 6 to 130) months. Sixty-seven
      percent of the patients received RT to the breast/chest wall and ipsilateral
      supraclavicular fossa. Of 243 patients, 51 (21%) were diagnosed with HT. The
      median time to the onset of HT was 27 (range; 5 to 64) months. There were no
      significant relationships observed between Dmin or V10 to V50 and HT. The surgery
      type, clinical stage, nodal status, RT field, Dmean, and Dmax were statistically
      significant predictors for HT in univariate analysis. The Dmean was the only
      prognostic factor predicting HT in multivariate analysis, and Dmean > 21 Gy was a
      threshold value for the evolvement of HT. In this study, we present evidence that
      postoperative irradiation of patients with breast cancer may frequently lead to
      HT. Patients who have received RT for breast cancer, especially irradiation on
      the supraclavicular region, may require thyroid function screening after RT.

PMID- 28502655
TI  - Earliest Mysticete from the Late Eocene of Peru Sheds New Light on the Origin of
      Baleen Whales.
AB  - Although combined molecular and morphological analyses point to a late middle
      Eocene (38-39 million years ago) origin for the clade Neoceti (Odontoceti,
      echolocating toothed whales plus Mysticeti, baleen whales, and relatives), the
      oldest known mysticete fossil dates from the latest Eocene (about 34 million
      years ago) of Antarctica [1, 2]. Considering that the latter is not the most
      stemward mysticete in recent phylogenies and that Oligocene toothed mysticetes
      display a broad morphological disparity most likely corresponding to contrasted
      ecological niches, the origin of mysticetes from a basilosaurid ancestor and its
      drivers are currently poorly understood [1, 3-8]. Based on an articulated
      cetacean skeleton from the early late Eocene (Priabonian, around 36.4 million
      years ago) of the Pisco Basin, Peru, we describe a new archaic tooth-bearing
      mysticete, Mystacodon selenensis gen. et sp. nov. Being the geologically oldest
      neocete (crown group cetacean) and the earliest mysticete to branch off described
      so far, the new taxon is interpreted as morphologically intermediate between
      basilosaurids and later toothed mysticetes, providing thus crucial information
      about the anatomy of the skull, forelimb, and innominate at these critical
      initial stages of mysticete evolution. Major changes in the morphology of the
      oral apparatus (including tooth wear) and flipper compared to basilosaurids
      suggest that suction and possibly benthic feeding represented key, early
      ecological traits accompanying the emergence of modern filter-feeding baleen
      whales' ancestors.

PMID- 28502656
TI  - Temporal Cohorts of Lineage-Related Neurons Perform Analogous Functions in
      Distinct Sensorimotor Circuits.
AB  - Neuronal stem cell lineages are the fundamental developmental units of the brain,
      and neuronal circuits are the fundamental functional units of the brain.
      Determining lineage-circuitry relationships is essential for deciphering the
      developmental logic of circuit assembly. While the spatial distribution of
      lineage-related neurons has been investigated in a few brain regions [1-9], an
      important, but unaddressed question is whether temporal information that
      diversifies neuronal progeny within a single lineage also impacts circuit
      assembly. Circuits in the sensorimotor system (e.g., spinal cord) are thought to
      be assembled sequentially [10-14], making this an ideal brain region for
      investigating the circuit-level impact of temporal patterning within a lineage.
      Here, we use intersectional genetics, optogenetics, high-throughput behavioral
      analysis, single-neuron labeling, connectomics, and calcium imaging to determine
      how a set of bona fide lineage-related interneurons contribute to sensorimotor
      circuitry in the Drosophila larva. We show that Even-skipped lateral interneurons
      (ELs) are sensory processing interneurons. Late-born ELs contribute to a
      proprioceptive body posture circuit, whereas early-born ELs contribute to a
      mechanosensitive escape circuit. These data support a model in which a single
      neuronal stem cell can produce a large number of interneurons with similar
      functional capacity that are distributed into different circuits based on birth
      timing. In summary, these data establish a link between temporal specification of
      neuronal identity and circuit assembly at the single-cell level.

PMID- 28502657
TI  - RPL10L Is Required for Male Meiotic Division by Compensating for RPL10 during
      Meiotic Sex Chromosome Inactivation in Mice.
AB  - The mammalian sex chromosomes have undergone profound changes during their
      evolution from an ancestral pair of autosomes [1-4]. Specifically, the X
      chromosome has acquired a paradoxical sex-biased function by redistributing gene
      contents [5, 6] and has generated a disproportionately high number of retrogenes
      that are located on autosomes and exhibit male-biased expression patterns [6].
      Several selection-based models have been proposed to explain this phenomenon,
      including a model of sexual antagonism driving X inactivation (SAXI) [6-8] and a
      compensatory mechanism based on meiotic sex chromosome inactivation (MSCI) [6, 8
      11]. However, experimental evidence correlating the function of X-chromosome
      derived autosomal retrogenes with evolutionary forces remains limited [12-17].
      Here, we show that the deficiency of Rpl10l, a murine autosomal retrogene of
      Rpl10 with testis-specific expression, disturbs ribosome biogenesis in late
      prophase spermatocytes and prohibits the transition from prophase into metaphase
      of the first meiotic division, resulting in male infertility. Rpl10l expression
      compensates for the lack of Rpl10, which exhibits a broad expression pattern but
      is subject to MSCI during spermatogenesis. Importantly, ectopic expression of
      RPL10L prevents the death of cultured RPL10-deficient somatic cells, and Rpl10l
      promoter-driven transgenic expression of Rpl10 in spermatocytes restores
      spermatogenesis and fertility in Rpl10l-deficient mice. Our results demonstrate
      that Rpl10l plays an essential role during the meiotic stage of spermatogenesis
      by compensating for MSCI-mediated transcriptional silencing of Rpl10. These data
      provide direct evidence for the compensatory hypothesis and add novel insight
      into the evolution of X-chromosome-derived autosomal retrogenes and their role in
      male fertility.

PMID- 28502658
TI  - Spontaneous Rapid Odor Source Localization Behavior Requires Interhemispheric
      Communication.
AB  - Navigation, finding food sources, and avoiding danger critically depend on the
      identification and spatial localization of airborne chemicals. When monitoring
      the olfactory environment, rodents spontaneously engage in active olfactory
      sampling behavior, also referred to as exploratory sniffing [1]. Exploratory
      sniffing is characterized by stereotypical high-frequency respiration, which is
      also reliably evoked by novel odorant stimuli [2, 3]. To study novelty-induced
      exploratory sniffing, we developed a novel, non-contact method for measuring
      respiration by infrared (IR) thermography in a behavioral paradigm in which novel
      and familiar stimuli are presented to head-restrained mice. We validated the
      method by simultaneously performing nasal pressure measurements, a commonly used
      invasive approach [2, 4], and confirmed highly reliable detection of inhalation
      onsets. We further discovered that mice actively orient their nostrils toward
      novel, previously unexperienced, smells. In line with the remarkable speed of
      olfactory processing reported previously [3, 5, 6], we find that mice initiate
      their response already within the first sniff after odor onset. Moreover,
      transecting the anterior commissure (AC) disrupted orienting, indicating that the
      orienting response requires interhemispheric transfer of information. This
      suggests that mice compare odorant information obtained from the two bilaterally
      symmetric nostrils to locate the source of the novel odorant. We further
      demonstrate that asymmetric activation of the anterior olfactory nucleus (AON) is
      both necessary and sufficient for eliciting orienting responses. These findings
      support the view that the AON plays an important role in the internostril
      difference comparison underlying rapid odor source localization.

PMID- 28502660
TI  - Beauty Requires Thought.
AB  - The experience of beauty is a pleasure, but common sense and philosophy suggest
      that feeling beauty differs from sensuous pleasures such as eating or sex.
      Immanuel Kant [1, 2] claimed that experiencing beauty requires thought but that
      sensuous pleasure can be enjoyed without thought and cannot be beautiful. These
      venerable hypotheses persist in models of aesthetic processing [3-7] but have
      never been tested. Here, participants continuously rated the pleasure felt from a
      nominally beautiful or non-beautiful stimulus and then judged whether they had
      experienced beauty. The stimuli, which engage various senses, included seeing
      images, tasting candy, and touching a teddy bear. The observer reported the
      feelings that the stimulus evoked. The time course of pleasure, across stimuli,
      is well-fit by a model with one free parameter: pleasure amplitude. Pleasure
      amplitude increases linearly with the feeling of beauty. To test Kant's claim of
      a need for thought, we reduce cognitive capacity by adding a "two-back" task to
      distract the observer's thoughts. The distraction greatly reduces the beauty and
      pleasure experienced from stimuli that otherwise produce strong pleasure and
      spares that of less-pleasant stimuli. We also find that strong pleasure is always
      beautiful, whether produced reliably by beautiful stimuli or just occasionally by
      sensuous stimuli. In sum, we confirm Kant's claim that only the pleasure
      associated with feeling beauty requires thought and disprove his claim that
      sensuous pleasures cannot be beautiful.

PMID- 28502659
TI  - APC/CCdh1 Enables Removal of Shugoshin-2 from the Arms of Bivalent Chromosomes by
      Moderating Cyclin-Dependent Kinase Activity.
AB  - In mammalian females, germ cells remain arrested as primordial follicles.
      Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of
      chromosomes, and their eventual alignment on metaphase plates. At the first
      meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20
      (APC/CCdc20) activates separase and thereby destroys cohesion along chromosome
      arms. Because cohesion around centromeres is protected by shugoshin-2, sister
      chromatids remain attached through centromeric/pericentromeric cohesin. We show
      here that, by promoting proteolysis of cyclins and Cdc25B at the germinal vesicle
      (GV) stage, APC/C associated with the Cdh1 protein (APC/CCdh1) delays the
      increase in Cdk1 activity, leading to germinal vesicle breakdown (GVBD). More
      surprisingly, by moderating the rate at which Cdk1 is activated following GVBD,
      APC/CCdh1 creates conditions necessary for the removal of shugoshin-2 from
      chromosome arms by the Aurora B/C kinase, an event crucial for the efficient
      resolution of chiasmata.

PMID- 28502661
TI  - An Adenosine Receptor for Olfaction in Fish.
AB  - Nucleotides released from food sources into environmental water are supposed to
      act as feeding cues for many fish species. However, it remains unknown how fish
      can sensitively detect those nucleotides. Here we discover a novel olfactory
      mechanism for ATP sensing in zebrafish. Upon entering into the nostril, ATP is
      efficiently converted into adenosine through enzymatic reactions of two ecto
      nucleotidases expressed in the olfactory epithelium. Adenosine subsequently
      activates a small population of olfactory sensory neurons expressing a novel
      adenosine receptor A2c that is unique to fishes and amphibians. The information
      is then transmitted to a single glomerulus in the olfactory bulb and further to
      four regions in higher olfactory centers. These results provide conclusive
      evidence for a sophisticated enzyme-linked receptor mechanism underlying
      detection of ATP as a food-derived attractive odorant linking to foraging
      behavior that is crucial and common to aquatic lower vertebrates.

PMID- 28502664
TI  - The utility of susceptibility-weighted imaging to evaluate the extent of iron
      accumulation in the choroid plexus of patients with beta-thalassaemia major.
AB  - AIM: To assess iron accumulation in the choroid plexus of beta-thalassaemia
      patients using fast spin echo (FSE) T2-weighted, gradient echo (GRE) T2*
      weighted, susceptibility-weighted imaging (SWI) and compare the results.
      MATERIALS AND METHODS: Eighteen patients with transfusion-dependent beta
      thalassaemia and the control group underwent magnetic resonance imaging (MRI)
      examinations. Signal intensities were separately evaluated using a "number of
      hypointensity in the choroid plexus" (NHICP) grading system on axial FSE T2
      weighted, GRE T2*-weighted, and SWI images. The NHICP grading system scores were
      compared using the chi-squared test. Spearman's correlation analysis was used to
      explore relationships between the variables and NHICP grading system scores.
      RESULTS: The sensitivity of each technique was calculated: FSE T2-weighted
      imaging=0.17, GRE T2*-weighted imaging=0.48, and SWI=0.81. Three-sample test for
      equality of proportions showed that chi-squared=74.85, df=2, p<0.0001. All of the
      FSE T2-weighted, GRE T2*-weighted, and SWI images differed significantly in terms
      of their capacity to reveal iron accumulation in the choroid plexus. Of the three
      methods, SWI was the most sensitive. CONCLUSIONS: SWI is useful for revealing
      iron deposition in the brains of beta-thalassaemia patients, especially those in
      the early stages of disease, and it can be used to predict disease prognosis. The
      present study contributes to an understanding of the important role played by the
      choroid plexus in brain iron metabolism.

PMID- 28502663
TI  - Memory Reactivation Enables Long-Term Prevention of Interference.
AB  - The ability of the human brain to successively learn or perform two competing
      tasks constitutes a major challenge in daily function. Indeed, exposing the brain
      to two different competing memories within a short temporal offset can induce
      interference, resulting in deteriorated performance in at least one of the
      learned memories [1-4]. Although previous studies have investigated online
      interference and its effects on performance [5-13], whether the human brain can
      enable long-term prevention of future interference is unknown. To address this
      question, we utilized the memory reactivation-reconsolidation framework [2, 12]
      stemming from studies at the synaptic level [14-17], according to which
      reactivation of a memory enables its update. In a set of experiments, using the
      motor sequence learning task [18] we report that a unique pairing of reactivating
      the original memory (right hand) in synchrony with novel memory trials (left
      hand) prevented future interference between the two memories. Strikingly, these
      effects were long-term and observed a month following reactivation. Further
      experiments showed that preventing future interference was not due to practice
      per se, but rather specifically depended on a limited time window induced by
      reactivation of the original memory. These results suggest a mechanism according
      to which memory reactivation enables long-term prevention of interference,
      possibly by creating an updated memory trace integrating original and novel
      memories during the reconsolidation time window. The opportunity to induce a long
      term preventive effect on memories may enable the utilization of strategies
      optimizing normal human learning, as well as recovery following neurological
      insults.

PMID- 28502662
TI  - "What Not" Detectors Help the Brain See in Depth.
AB  - Binocular stereopsis is one of the primary cues for three-dimensional (3D) vision
      in species ranging from insects to primates. Understanding how the brain extracts
      depth from two different retinal images represents a tractable challenge in
      sensory neuroscience that has so far evaded full explanation. Central to current
      thinking is the idea that the brain needs to identify matching features in the
      two retinal images (i.e., solving the "stereoscopic correspondence problem") so
      that the depth of objects in the world can be triangulated. Although intuitive,
      this approach fails to account for key physiological and perceptual observations.
      We show that formulating the problem to identify "correct matches" is suboptimal
      and propose an alternative, based on optimal information encoding, that mixes
      disparity detection with "proscription": exploiting dissimilar features to
      provide evidence against unlikely interpretations. We demonstrate the role of
      these "what not" responses in a neural network optimized to extract depth in
      natural images. The network combines information for and against the likely depth
      structure of the viewed scene, naturally reproducing key characteristics of both
      neural responses and perceptual interpretations. We capture the encoding and
      readout computations of the network in simple analytical form and derive a
      binocular likelihood model that provides a unified account of long-standing
      puzzles in 3D vision at the physiological and perceptual levels. We suggest that
      marrying detection with proscription provides an effective coding strategy for
      sensory estimation that may be useful for diverse feature domains (e.g., motion)
      and multisensory integration.

PMID- 28502665
TI  - Can the Contrast-Enhanced Ultrasound Washout Rate Be Used to Predict
      Microvascular Invasion in Hepatocellular Carcinoma?
AB  - The objective of this study was to investigate use of the washout rate of
      hepatocellular carcinoma on contrast-enhanced ultrasound (CEUS) for pre-operative
      determination of the presence of microvascular invasion. The study included 271
      patients who underwent liver resection for hepatocellular carcinoma between April
      2008 and December 2012, and were examined with contrast-enhanced ultrasound
      before surgery. Patients were followed up at 3-mo intervals for 3 y. Four washout
      patterns were classified according to the start time of washout: rapid, portal,
      delayed and slow. Rapid washout, presence of two or more tumors and tumor size
      >=5 cm were identified as independent pre-operative predictors of microvascular
      invasion on multivariate analysis. Recurrence rates for patients with none, one,
      two or three predictors were 22.6%, 34.7%, 57.6% and 75.0%, respectively. In
      combination with tumor number and tumor size, contrast-enhanced ultrasound
      washout rate may have a role in identifying hepatocellular carcinoma patients
      with microvascular invasion.

PMID- 28502667
TI  - Mechanosensitivity: From Aristotle's sense of touch to cardiac mechano-electric
      coupling.
AB  - Scientific interest in mechanosensation likely commenced with Aristotle's
      description of the sense of touch in his treatise de Anima [On the Soul].
      Considering touch as a vital sense distributed over the whole body, the
      philosopher outlined a "physiological concept" at the macro-level already 2400
      years ago. From this starting point, we outline the onset of modern sensory
      physiology during the early 19th century. Physiologists distinguished between
      outer and inner senses at that time, without, however, referring to specific
      receptors or nerves. We then outline how research on four topics concerning
      cardiac mechano-electric coupling developed up until the 1960's (cardio
      respiratory coupling, Bainbridge reflex, Bezold-Jarisch reflex, stretch-induced
      arrhythmias). Following the discovery of macroscopic phenomena (e.g. change of
      heart rate, induced by atrial distension) during that period, researchers sought
      to identify the pertinent receptors and reflex loops, while nowadays the
      underlying subcellular mechanisms such as stretch-activated ion channels are
      under investigation.

PMID- 28502666
TI  - Purification and characterisation of the fission yeast Ndc80 complex.
AB  - The Ndc80 complex is a conserved outer kinetochore protein complex consisting of
      Ndc80 (Hec1), Nuf2, Spc24 and Spc25. This complex comprises a major, if not the
      sole, platform with which the plus ends of the spindle microtubules directly
      interact. In fission yeast, several studies indicate that multiple microtubule
      associated proteins including the Dis1/chTOG microtubule polymerase and the
      Mal3/EB1 microtubule plus-end tracking protein directly or indirectly bind Ndc80,
      thereby ensuring stable kinetochore-microtubule attachment. However, the
      purification of the Ndc80 complex from this yeast has not been achieved, which
      hampers the in-depth investigation as to how the outer kinetochore attaches to
      the plus end of the spindle microtubule. Here we report the two-step purification
      of the fission yeast Ndc80 holo complex from bacteria. First, we purified
      separately two sub-complexes consisting of Ndc80-Nuf2 and Spc24-Spc25. Then,
      these two sub-complexes were mixed and applied to size-exclusion chromatography.
      The reconstituted Ndc80 holo complex is composed of four subunits with equal
      stoichiometry. The complex possesses microtubule-binding activity, and Total
      Internal Reflection Fluorescence (TIRF)-microscopy assays show that the complex
      binds the microtubule lattice. Interestingly, unlike the human complex, the
      fission yeast complex does not track depolymerising microtubule ends. Further
      analysis shows that under physiological ionic conditions, the Ndc80 holo complex
      does not detectably bind Dis1, but instead it interacts with Mal3/EB1, by which
      the Ndc80 complex tracks the growing microtubule plus end. This result
      substantiates the notion that the Ndc80 complex plays a crucial role in
      establishment of the dynamic kinetochore-microtubule interface by cooperating
      with chTOG and EB1.

PMID- 28502668
TI  - Spectrographic and Electroglottographic Findings of Religious Vocal Performers in
      Duzce Province of Turkey.
AB  - OBJECTIVES: In the present study, the register phenomenon and spectral
      characteristics of vocal styles used by vocal performers in a Muslim community
      were investigated. METHODS: Electroglottography was performed on 17 subjects,
      whereas spectrography was performed on 18 subjects, and 16 of these subjects
      participated in both parts of the study. RESULTS: We observed that the
      participants used chest register in voice production and there was no change in
      this situation related to the increase in frequency. It was found that Western
      opera singers' formant cluster did not exist in their normal speech and
      performance voice spectrum. Generally, there were clear energy peaks at the 3- to
      4-kHz spectral region in their performance voice, but this peak did not appear in
      the daily speech voice. CONCLUSIONS: It was concluded that a bunched F3, F4, and
      F5 is a critical prerequisite in the production of a calling formant cluster.
      However, it was observed that in certain cases, this phenomenon was produced only
      with bunching of F4 and F5 or with an increased F4 energy level. Although an
      increase in F3 assists in the production of the calling formant cluster, the main
      source of the calling formant cluster was the decrease in F4 and F5 frequencies,
      and the main contribution came from F5, which was fairly decreased. Moreover, it
      was found that a decreased closed quotient value caused a raise in the relative
      level of calling formant cluster (Lcfc) value. In conclusion, our results
      indicate that the production of the calling formant cluster is based not only on
      vocal tract properties but also on glottal settings.

PMID- 28502671
TI  - Integrating clinical metabolomics-based biomarker discovery and clinical
      pharmacology to enable precision medicine.
AB  - Novel developments in biomarkers discovery are essential in modern health care,
      notably in treatment individualization and precision medicine. Clinical
      metabolomics, which aims to identify small molecule metabolites present in
      patient-derived samples, has attracted much attention to support discovery of
      novel biomarkers. However, the step from discriminatory features of disease
      states towards biomarkers that can truly individualize treatments is challenging.
      Biomarkers used for treatment individualization can either be dynamic or static
      prognostic biomarkers. Dynamic biomarkers are relevant for describing the
      clinical response, including dynamical disease progression and associated
      treatment response. Static (prognostic) biomarkers do not describe but rather
      predict a clinical response, and typically reflect aspects of the physiological
      state of a patient related to drug treatment response or disease progression
      dynamics. Pharmacokinetic-pharmacodynamic (PK-PD) modeling represents an
      established approach for drug treatment individualization based on drug exposure
      or treatment response biomarkers, as well as for the description of disease
      progression dynamics. Here, we discuss how novel treatment individualization
      biomarkers can be identified using a clinical metabolomics-based approach, and
      how concepts inspired from the field of PK-PD modeling can be integrated in this
      process in order to increase the clinical relevance of identified biomarkers and
      precision medicine.

PMID- 28502669
TI  - Biomimetic tendon extracellular matrix composite gradient scaffold enhances
      ligament-to-bone junction reconstruction.
AB  - : Management of ligament/tendon-to-bone-junction healing remains a formidable
      challenge in the field of orthopedic medicine to date, due to deficient
      vascularity and multi-tissue transitional structure of the junction. Numerous
      strategies have been employed to improve ligament-bone junction healing,
      including delivery of stem cells, bioactive factors, and synthetic materials, but
      these methods are often inadequate at recapitulating the complex structure
      function relationships at native tissue interfaces. Here, we developed an easily
      fabricated and effective biomimetic composite to promote the regeneration of
      ligament-bone junction by physically modifying the tendon extracellular matrix
      (ECM) into a Random-Aligned-Random composite using ultrasound treatment. The
      differentiation potential of rabbit bone marrow stromal cells on the modified ECM
      were examined in vitro. The results demonstrated that the modified ECM enhanced
      expression of chondrogenesis and osteogenesis-associated epigenetic genes
      (Jmjd1c, Kdm6b), transcription factor genes (Sox9, Runx2) and extracellular
      matrix genes (Col2a1, Ocn), resulting in higher osteoinductivity than the
      untreated tendon ECM in vitro. In the rabbit anterior cruciate ligament (ACL)
      reconstruction model in vivo, micro-computed tomography (Micro-CT) and
      histological analysis showed that the modified Random-Aligned-Random composite
      scaffold enhanced bone and fibrocartilage formation at the interface, more
      efficaciously than the unmodified tendon ECM. Therefore, these results
      demonstrated that the biomimetic Random-Aligned-Random composite could be a
      promising scaffold for ligament/tendon-bone junction repair. STATEMENT OF
      SIGNIFICANCE: The native transitional region consists of several distinct yet
      contiguous tissue regions, composed of soft tissue, non-calcified fibrocartilage,
      calcified fibrocartilage, and bone. A stratified graft whose phases are
      interconnected with each other is essential for supporting the formation of
      functionally continuous multi-tissue regions. Various techniques have been
      attempted to improve adherence of the ligament/tendon graft to bone, including
      utilization of stem cells, growth factors and biomaterials, but these methods are
      often inadequate at recapitulating the complex structure-function relationships
      at native tissue interfaces. Here, we developed an easily-fabricated and
      effective biomimetic composite to promote the regeneration of ligament-bone
      junction by physically modifying the tendon extracellular matrix (ECM) into a
      Random-Aligned-Random composite using ultrasound treatment. The modified ECM
      enhanced expression of chondrogenesis and osteogenesis-associated epigenetic
      genes expression in vitro. In the rabbit anterior crucial ligament reconstruction
      model in vivo, results showed that the modified Random-Aligned-Random composite
      enhances the bone and fibrocartilage formation in the interface, proving to be
      more efficient than the unmodified tendon ECM. Therefore, these results
      demonstrated that the biomimetic Random-Aligned-Random composite could be a
      promising scaffold for ligament/tendon-bone junction repair.

PMID- 28502670
TI  - Direct quantification of dual protein adsorption dynamics in three dimensional
      systems in presence of cells.
AB  - : Understanding the composition of the adsorbed protein layer on a biomaterial
      surface is of an extreme importance as it directs the primary biological
      response. Direct detection using labeled proteins and indirect detection based on
      enzymatic assays or changes to mass, refractive index or density of a surface
      have been so far established. Nevertheless, using current methodologies,
      detection of multiple proteins simultaneously and particularly in a three
      dimensional (3D) substrates is challenging, with the exception of radiolabeling.
      Here using fluorescence molecular tomography (FMT), we present a non-destructive
      and versatile approach to quantify adsorption of multiple proteins within 3D
      environments and reveal the dynamics of adsorption of human serum albumin (HSA)
      and fibrinogen (Fib) on 3D polymeric scaffold. Furthermore, we show that serum
      starved human articular chondrocytes in 3D environment preferentially uptake HSA
      over Fib and to our knowledge this represents the first example of direct
      visualization and quantification of protein adsorption in a 3D cell culture
      system. STATEMENT OF SIGNIFICANCE: The biomaterial surface upon exposure to
      biological fluids is covered by a layer of proteins, which is modified over a
      period of time and dictates the fate of the biomaterial. In this study, we
      present and validate a new methodology for quantification of protein adsorption
      on to a three-dimensional polymer scaffold from unitary and binary systems, using
      fluorescence molecular tomography, an optical trans-illumination technique with
      picomolar sensitivity. In additional to being able to follow behavior of two
      proteins simultaneously, this methodology is also suitable for studying protein
      uptake in cells situated in a polymer environment. The ability to follow protein
      adsorption/uptake in a continuous manner opens up new possibilities to study the
      role of serum proteins in biomaterial compatibility.

PMID- 28502672
TI  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel
      resistance in P-glycoprotein overexpressing cancer cells.
AB  - The efficacy of microtubule targeting agents in cancer treatment has been
      compromised by the development of drug resistance that may involve both, P
      glycoprotein overexpression and the changes in beta-tubulin isoforms' expression.
      The anti-Topoisomerase II activity of methyl 4-((E)-2
      (methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein,
      we further evaluated this propargylic enol ether derivative and found that it
      exerts inhibitory effect on tubulin polymerization by binding to colchicine
      binding site. DTA0100 mitotic arrest properties were investigated in two multi
      drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal
      carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell
      lines to DTA0100 was not significantly changed in contrast to microtubule
      targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly
      induced microtubule depolymerization, leading to disturbance of cell cycle
      kinetics and subsequent apoptosis. The fine-tuning in beta-tubulin isoforms
      expression observed in multi-drug resistant cancer cells may influence the
      efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in
      both multi-drug resistant cancer cell lines without inducing the increase in P
      glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of
      Topoisomerase II and microtubule formation could be considered as multi-potent
      anticancer agent. Besides, it is able to overcome the problem of drug resistance
      that emerges in the therapeutic approaches with either Topoisomerase II or
      microtubule targeting agents.

PMID- 28502673
TI  - Glucosamine modulates propranolol pharmacokinetics via intestinal permeability in
      rats.
AB  - Propranolol (PROP) undergoes extensive first-pass metabolism by the liver
      resulting in a relatively low bioavailability (13-23%); thus, multiple oral doses
      are required to achieve therapeutic effect. Since some studies have reported that
      glucosamine (GlcN) can increase the bioavailability of some drugs, therefore, it
      is aimed to study whether GlcN can change the pharmacokinetic parameters of PROP,
      thus modulating its bioavailability. When PROP was orally co-administered with
      GlcN (200mg/kg) to rats, PROP area under curve (AUC) and maximum concentration
      (Cmax) were significantly decreased by 43% (p<0.01) and 33% (p<0.05),
      respectively. In line with the in vivo results, in silico simulations confirmed
      that GlcN decreased rat intestinal effective permeability (Peff) and increased
      PROP clearance by 50%. However, in situ single pass intestinal perfusion (SPIP)
      experiments showed that GlcN significantly increased PROP serum levels (p<0.05).
      Furthermore, GlcN decreased PROP disposition/distribution into cultured
      hepatocytes in concentration dependent manner. Such change in the interaction
      pattern between GlcN and PROP might be attributed to the environment of the
      physiological buffer used in the in vitro experiments (pH7.2) versus the oral
      administration and thus, enhanced PROP permeability. Nevertheless, such
      enhancement was not detected when everted gut sacks were incubated with both
      drugs at the same pH in vitro. In conclusion, GlcN decreased PROP serum levels in
      rats in a dose-dependent manner. Such interaction might be attributed to
      decreased intestinal permeability and enhanced clearance of PROP in the presence
      of GlcN. Further investigations are still warranted to explain the in vitro
      inhibitory action of GlcN on PROP hepatocytes disposition and the involvement of
      GlcN in the intestinal and hepatic metabolizing enzymes of PROP at different
      experimental conditions.

PMID- 28502675
TI  - Genotype-guided dosing of warfarin through modeling and simulation.
AB  - Current genotype-guided algorithms for warfarin dosing fail to deliver optimal
      performance in two aspects: 1) these algorithms are not able to achieve the same
      level of benefits in non-white populations, since they were developed based on
      multivariate regression analysis with mostly European/White data and did not
      include genetic variants found frequently in non-white populations; 2) these
      algorithms do not account for the dynamic dose/response relationship and were
      limited in their usefulness to guide dosing during the initiation phase, as the
      possession of variant VKORC1 and/or CYP2C9 polymorphisms has been associated with
      a more rapid attainment of target international normalized ratio (INR) and higher
      risk of over-anticoagulation even in genotype-guided patients. To address these
      shortcomings, we report on the novel use of a previously published
      kinetic/pharmacodynamic (K/PD) model to develop a warfarin dosing nomogram to be
      used across genotypes and ethnicities. Our approach leverages data from both
      ethnically diverse and European patients, while accounting for the differential
      dose/response behaviors due to VKORC1 and CYP2C9 genotypes. According to
      simulations, the utilization of our dosing nomogram could enable effective
      attainment of therapeutic INR within one week in both ethnically diverse and
      European populations, while maintaining uniform INR response profiles across
      genotypes. Furthermore, in silico clinical trial simulations using the K/PD model
      could be a feasible approach to help to further refine our dosing nomogram to be
      more applicable in the clinical setting and explore possible outcomes even before
      prospective clinical trials are initiated.

PMID- 28502674
TI  - Evidence-based drug treatment for special patient populations through model-based
      approaches.
AB  - The majority of marketed drugs remain understudied in some patient populations
      such as pregnant women, paediatrics, the obese, the critically-ill, and the
      elderly. As a consequence, currently used dosing regimens may not assure optimal
      efficacy or minimal toxicity in these patients. Given the vulnerability of some
      subpopulations and the challenges and costs of performing clinical studies in
      these populations, cutting-edge approaches are needed to effectively develop
      evidence-based and individualized drug dosing regimens. Five key issues are
      presented that are essential to support and expedite the development of drug
      dosing regimens in these populations using model-based approaches: 1) model
      development combined with proper validation procedures to extract as much valid
      information from available study data as possible, with limited burden to
      patients and costs; 2) integration of existing data and the use of prior
      pharmacological and physiological knowledge in study design and data analysis, to
      further develop knowledge and avoid unnecessary or unrealistic (large) studies in
      vulnerable populations; 3) clinical proof-of-principle in a prospective
      evaluation of a developed drug dosing regimen, to confirm that a newly proposed
      regimen indeed results in the desired outcomes in terms of drug concentrations,
      efficacy, and/or safety; 4) pharmacodynamics studies in addition to
      pharmacokinetics studies for drugs for which a difference in disease progression
      and/or in exposure-response relation is anticipated compared to the reference
      population; 5) additional efforts to implement developed dosing regimens in
      clinical practice once drug pharmacokinetics and pharmacodynamics have been
      characterized in special patient populations. The latter remains an important
      bottleneck, but this is essential to truly realize evidence-based and
      individualized drug dosing for special patient populations. As all tools required
      for this purpose are available, we have the moral and societal obligation to make
      safe and effective pharmacotherapy available for these patients too.

PMID- 28502676
TI  - The influence of drug distribution and drug-target binding on target occupancy:
      The rate-limiting step approximation.
AB  - The influence of drug-target binding kinetics on target occupancy can be
      influenced by drug distribution and diffusion around the target, often referred
      to as "rebinding" or "diffusion-limited binding". This gives rise to a decreased
      decline of the drug-target complex concentration as a result of a locally higher
      drug concentration that arises around the target, which leads to prolonged target
      exposure to the drug. This phenomenon has been approximated by the steady-state
      approximation, assuming a steady-state concentration around the target. Recently,
      a rate-limiting step approximation of drug distribution and drug-target binding
      has been published. However, a comparison between both approaches has not been
      made so far. In this study, the rate-limiting step approximation has been
      rewritten into the same mathematical format as the steady-state approximation in
      order to compare the performance of both approaches for the investigation of the
      influence of drug-target binding kinetics on target occupancy. While both
      approximations clearly indicated the importance of kon and high target
      concentrations, it was shown that the rate-limiting step approximation is more
      accurate than the steady-state approximation, especially when dissociation is
      fast compared to association and distribution out of the binding compartment. It
      is therefore concluded that the new rate-limiting step approximation is to be
      preferred for assessing the influence of binding kinetics on local target site
      concentrations and target occupancy.

PMID- 28502677
TI  - Biophysical study of bevacizumab structure and bioactivity under thermal and pH
      stresses.
AB  - The evaluation of the structural stability and bioactivity of monoclonal
      antibodies (mAb) is a crucial step in the development of mAb therapeutic based
      products, since immunogenicity needs to be avoided. In the present work, a study
      was carried out to understand the changes on the structure and bioactivity of
      mAbs induced by different pH and temperature values. Structural changes of
      bevacizumab were monitored using fluorescence spectroscopy, circular dichroism
      (CD) and Attenuated total reflectance-Fourier transform infrared spectroscopy
      (ATR-FTIR). The secondary and tertiary structural content was monitored at six
      different pH values and at room temperature, upon heating up to 85 degrees C and
      upon cooling down to 20 degrees C. Furthermore, the temperature induced
      conformational changes were continuously monitored from 20 degrees C to 85
      degrees C using fluorescence spectroscopy and circular dichroism, allowing to
      monitor the melting temperature of the protein at different pH values. The
      results showed that the thermal denaturation of bevacizumab was irreversible at
      all pH value. The conformational changes induced by pH were higher at extreme pH
      values (5, 9 and 10) than neutral pH. Thermal stability studies showed that pH6
      was the pH that confer bevacizumab the highest structural stability. These
      studies were confirmed by in vitro studies, where bevacizumab's bioactivity was
      measured by cell viability/proliferation at all pH values at room temperature,
      and it was found a higher bioactivity for pH6. Biophysical and biological studies
      were correlated in order to understand the importance of the modifications in
      bevacizumab structural content on its bioactivity. However, a decrease in
      bevacizumab's bioactivity was observed for pH8, 9 and 10. Overall, this work
      demonstrated the usefulness of the spectroscopy techniques for estimating the
      stability of therapeutic mAb during formulation development.

PMID- 28502678
TI  - IL-10-producing regulatory B cells (B10 cells), IL-17+ T cells and autoantibodies
      in systemic sclerosis.
AB  - We aimed to analyze IL-10+ Breg (B10) cells, found to be reduced in systemic
      sclerosis (SSc), in relation to SSc-specific autoAbs and IL-17+ and IFNgamma+ T
      cells in SSc. Peripheral blood B10 cells from 26 patients with SSc positive for
      anti-Topo I or anti-Cen autoAbs, and 12 healthy controls (HC) were studied by
      flow cytometry. IL-17+ and IFNgamma+ T cells were also studied. B10 cells did not
      correlate with anti-Topo I or anti-Cen Ab levels but were inversely correlated
      with IL-17+ CD3+ cells and IFNgamma+ CD3+ cells. IL-17+ CD3+ cells did not
      correlate with autoAb levels, but IFN-gamma+ CD3+ cells were inversely correlated
      with anti-Topo I levels. In conclusion, in SSc, B10 cells did not correlate with
      SSc-specific autoAbs and exhibited an inverse correlation with IL-17+ T cells and
      IFNgamma+ T cells.

PMID- 28502680
TI  - Semaphorin 3A: Is a key player in the pathogenesis of asthma.
AB  - Immune semaphorins are key players in regulating immune mediated inflammation.
      Semaphorin3A (sema3A) a secreted and membrane bound member of this family, is
      well reported for its properties in maintaining self-tolerance. Semaphorin3A was
      recognized to be a marker for T-regulatory cells (Tregs), and as such is a useful
      tool for assessing the status of these cells in preventing immune mediated
      diseases. This study was designed aiming to evaluate how sema3A is possibly
      involved in bronchial asthma. Here, we found sema3A serum levels and the
      expression of sema3A on Tregs significantly lower in patients with moderate to
      severe asthma when compared to healthy individuals. Co-culture of condition
      medium with 2mcg/ml of recombinant human sema3A with CD4+ T cells, increased the
      expression of FoxP3 in Tregs, suggesting sema3A a potent immune-regulator of
      inflammation including that of asthma. Further in-vivo studies will better
      establish the beneficial effect of sema3A in regulating inflammation in asthma.

PMID- 28502679
TI  - The association between semaphorin 3A levels and gluten-free diet in patients
      with celiac disease.
AB  - Celiac disease (CD) is an inflammatory disease affecting the small intestine. We
      aim to assess serum level and expression of semaphorin 3A (Sema3A) on T
      regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac
      patients, 13 celiac patients on a gluten-free diet and 16 healthy controls
      included in the study. Sema3A protein level in the serum of celiac patients was
      significantly higher compared to healthy group (7.17+/-1.8ng/ml vs. 5.67+/
      1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in
      celiac patients compared to healthy subjects (p=0.009) and significantly lower in
      celiac patients compared to celiac patients on gluten free diet (p=0.04).
      Negative correlation was found between Sema3A on Teg cells and the level of IgA
      anti-tTG antibodies (r=-0.346, p<0.01) and anti-DGP (r=-0.448, p<0.01). This
      study suggests involvement of the Sema3A in the pathogenesis of CD.

PMID- 28502681
TI  - Cost Implications of Primary Versus Revision Surgery in Adult Spinal Deformity.
AB  - BACKGROUND: Adult spinal deformity (ASD) is an important problem to consider in
      the elderly. Although studies have examined the complications of ASD surgery and
      have compared functional and radiographic results of primary surgery versus
      revision, no studies have compared the costs of primary procedures with
      revisions. We assessed the in-hospital costs of these 2 surgery types in patients
      with ASD. METHODS: The PearlDiver Database, a database of Medicare records, was
      used in this study. Mutually exclusive groups of patients undergoing primary or
      revision surgery were identified. Patients in each group were queried for age,
      sex, and comorbidities. Thirty-day readmission rates, 30-day and 90-day
      complication rates, and postoperative costs of care were assessed with
      multivariate analysis. For analyses, significance was set at P < 0.001. RESULTS:
      The average reimbursement of the primary surgery cohort was $57,078 +/- $30,767.
      Reimbursement of revision surgery cohort was $52,999 +/- $27,658. The adjusted
      difference in average costs between the 2 groups is $4773 +/- $1069 (P < 0.001).
      The 30-day and 90-day adjusted difference in cost of care when sustaining any of
      the major medical complications in primary surgery versus revision surgery was
      insignificant. CONCLUSIONS: Patients undergoing primary and revision corrective
      procedures for ASD have similar readmission rates, lengths of stays, and
      complication rates. Our data showed a higher cost of primary surgery compared
      with revision surgery, although costs of sustaining postoperative complications
      were similar. This finding supports the decision to perform revision procedures
      in patients with ASD when indicated because neither outcomes nor costs are a
      hindrance to correction.

PMID- 28502682
TI  - Intrarectal Anesthesia in Neurosurgery.
AB  - In the early days of modern neurologic surgery, the inconveniences and potential
      dangers of general anesthesia by chloroform and ether using the so-called "open
      drop technique" led to the quest for alternative methods of anesthesia. This
      became all the more necessary, since patient positioning and the surgical
      arrangements often hindered the use of a drop bottle. One approach to solve this
      problem was intrarectal ether application. The present article aims to shed light
      on this original, less well-known anesthesia technique in the neurosurgical
      field.

PMID- 28502683
TI  - Surgical Management and Adverse Factors for Recurrence and Long-Term Survival in
      Patients with Hemangiopericytoma.
AB  - OBJECTIVE: Intracranial hemangiopericytoma is a rare tumor with high recurrence
      rate. We analyzed adverse factors for recurrence and survival of patients with
      hemangiopericytoma. METHODS: We retrospectively reviewed clinical data of 120
      patients (mean age, 42 years; 60 male patients) with hemangiopericytoma who were
      surgically treated in our hospital from December 2008 to January 2016. RESULTS:
      Gross total resection (GTR) rate was 71.7%. Postoperative adjuvant radiotherapy
      (PRT) was administered to 63 patients. After median follow-up period of 46.9
      months, 35 (29.1%) recurrences and 17 (14.1%) deaths were observed. Progression
      free survival (PFS) at 1, 3, and 5 years was 90.8%, 78.5%, and 68.0%, and
      corresponding overall survival rate was 99.2%, 93.7%, and 82.4%. Higher
      preoperative Karnofsky performance scale scores (hazard ratio [HR] = 0.896, 95%
      confidence interval [CI] = 0.845-0.950, P < 0.001), convex surface location (HR =
      2.151, 95% CI = 1.042-4.443, P = 0.038), and PRT (HR = 0.339, 95% CI = 0.159
      0.724, P = 0.005) were independent favorable factors for PFS. For overall
      survival, higher preoperative Karnofsky performance scale scores (HR = 0.914, 95%
      CI = 0.854-0.978, P = 0.009), GTR (HR = 0.291, 95% CI = 0.109-0.777, P = 0.014),
      and PRT (HR = 0.210, 95% CI = 0.060-0.734, P = 0.015) were independent favorable
      factors. In patients undergoing non-GTR, PRT significantly improved PFS (HR =
      0.252, 95% CI = 0.070-0.906, P = 0.035). CONCLUSIONS: This study revealed risk
      factors for PFS and overall survival to predict outcomes and determine
      treatments. GTR was attempted as frequently as possible, and PRT was recommended
      for patients with non-GTR or recurrence to improve tumor control.

PMID- 28502684
TI  - Metastatic Neuroendocrine Carcinoma of Unknown Origin Arising in the Femoral
      Nerve Sheath.
AB  - BACKGROUND: Metastatic neuroendocrine carcinoma of unknown origin is a rare
      condition, usually presenting with lesions in the liver and/or lung. We present
      the first reported case of a metastatic neuroendocrine carcinoma of unknown
      origin arising in the femoral nerve sheath. CASE DESCRIPTION: Magnetic resonance
      imaging demonstrated what was thought to be a schwannoma in the left femoral
      nerve sheath in the proximal femoral triangle, immediately inferior to the
      anterior inferior iliac spine. At the time of operation, the tumor capsule was
      invading surrounding tissue, as well as three trunks of the femoral nerve. The
      patient underwent a subtotal resection, preserving the integrity of the residual
      functioning femoral nerve trunks. Histologic evaluation determined that the tumor
      had features consistent with a metastatic neuroendocrine carcinoma of unknown
      primary origin. The patient recovered well postoperatively, and subsequent
      radiologic evaluation failed to demonstrate a potential primary site.
      Unfortunately, the patient re-presented with disease progression and was
      subsequently referred to palliative care. CONCLUSIONS: We recommend that there is
      a definite role for surgery in the management of solitary neuroendocrine
      carcinoma of unknown origin.

PMID- 28502685
TI  - Transorbital Glue Embolization of a Recurrent Venous Varix Using Real-Time Image
      Guidance in the Neuroangiography Suite.
AB  - Orbital lesions are challenging to access due to their location amid critical
      anatomic structures. Here, we demonstrate direct transorbital cannulation of an
      orbital venous varix using image guidance. A 36-year-old male was diagnosed with
      a left orbital venous varix approximately 5 years ago at an outside institution.
      He subsequently underwent surgery for direct intraoperative embolization of the
      venous varix followed by surgical resection. The patient recently presented to us
      with left eye pain, proptosis, double vision, and conjunctival hemorrhage
      precipitated by straining or lying flat. Orbital magnetic resonance imaging
      showed recurrence of the venous varix, which was then confirmed with digital
      subtraction angiography and intraprocedural computed tomography (DynaCT, Siemens
      Healthineers, Erlangen, Germany). Due to scarring from the previous surgery,
      percutaneous transorbital embolization of the venous varix was planned. The
      needle trajectory was determined and also visualized in real-time using image
      guidance (Needle Guidance, Siemens Healthineers). Once the needle reached the
      desired target, n-butyl cyanoacrylate glue (Codman Neuro, San Jose, California)
      was injected until nearly the entire venous varix was occluded. There were no
      complications, and at his postoperative visit the patient reported resolution of
      all symptoms.

PMID- 28502686
TI  - Customized Polymethylmethacrylate Cranioplasty Implants Using 3-Dimensional
      Printed Polylactic Acid Molds: Technical Note with 2 Illustrative Cases.
AB  - OBJECTIVES: Prefabricated customized cranioplasty implants are anatomically more
      accurate than manually shaped acrylic implants but remain costly. The authors
      describe a new cost-effective technique of producing customized
      polymethylmethacrylate (PMMA) cranioplasty implants with the use of prefabricated
      3-dimensional (3D) printed molds. METHODS: The first patient had a left frontal
      cranial defect after a craniotomy for a glial tumor. A 3D image of his skull was
      obtained from axial 0.6-mm computed tomography (CT) scan images. The image of the
      implant was generated by a digital subtraction mirror-imaging process using the
      normal side of his cranium as a model. The second patient had a bifrontal defect
      after the resection of an infected customized polyetheretherketone implant. A 3D
      image of the infected implant was directly obtained from an axial 0.6-mm CT scan
      before discarding it. The images were then used to produce for each patient a
      mold of the external surface of the cranium using a low-cost polylactic acid 3D
      printer. Intraoperatively, each mold was put in a sterile bag and then used to
      cast a customized PMMA implant subsequently trimmed before fixation. RESULTS:
      Both patients had excellent cosmetic results and underwent postoperative CT scans
      that showed excellent restoration of the symmetrical contours of the cranium. No
      neurologic or infectious complications occurred over a 6-month follow-up for
      either patient. CONCLUSIONS: Making customized PMMA cranioplasty implants via 3D
      printed polylactic acid molds is a cost-effective technique for delayed
      reconstruction of various cranial defects.

PMID- 28502687
TI  - The Onodi Cell: An Anatomic Illustration.
AB  - This anatomic image demonstrates the sphenoethmoidal (Onodi) cell (a variant of
      the paranasal sinuses), the identification of which is critical to prevent
      neurovascular injury during endoscopic approaches to the sella and adjacent
      regions of the skull base.

PMID- 28502688
TI  - Evaluating Outcomes of Stand-Alone Anterior Lumbar Interbody Fusion: A Systematic
      Review.
AB  - BACKGROUND: Stand-alone anterior lumbar interbody fusion (ALIF) is an effective
      surgical approach for selected spinal pathologies. It avoids the morbidity and
      complications associated with instrumented ALIF, such as plate fixation and the
      traditionally used posterior approach. Despite improved disc space visualization
      and clearance, the associated posterior instability and increased risk of
      nonfusion present major challenges to this approach. The integral cage design
      aims to address these challenges by providing the necessary stabilization through
      intracorporeal screws. However, there is limited and controversial data available
      for stand-alone ALIF and integral cage fixation. To our knowledge, this is the
      first systematic review to evaluate recent findings on outcomes of stand-alone
      ALIF devices to explore areas of controversy and identify directions for future
      research. METHODS: Two reviewers conducted independent, systematic literature
      searches for appropriate studies in 5 electronic databases as per Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were
      filtered by the use of specified selection criteria, particularly exclusion of
      studies with supplementary fixation to ALIF and studies published before the year
      2000. A total of 17 studies met the criteria, and their data were comprehensively
      extracted and analyzed. RESULTS: The current literature is supportive of stand
      alone ALIF due to acceptable clinical outcomes, promising fusion rates and disc
      height restoration. However, data and outcomes remain preliminary, and there are
      numerous areas of controversy. CONCLUSIONS: There is evidence for the efficacy
      and safety of stand-alone ALIF. However, the extent of improvement based on
      specific indications for surgery remains unclear. Further investigation utilizing
      more methodologically rigorous studies of long-term outcomes is necessary to
      address these issues.

PMID- 28502689
TI  - Complicated Mild Traumatic Brain Injury and the Need for Imaging Surveillance.
AB  - OBJECTIVE: To evaluate the need for repeat head computed tomography (CT) in
      patients with complicated mild traumatic brain injury (TBI) determined
      nonoperative after the first head CT. METHODS: A total of 380 patients with mild
      TBI and a positive head CT not needing surgery were included. Changes between
      first and second head CT were categorized as decreased, increased, or stable.
      RESULTS: Three patients required neurosurgical intervention (0.8%) after the
      second CT. There were no significant differences in demographics including age,
      gender, alcohol consumption, anticoagulation status, time between first and
      second CT, Glasgow Coma Scale score at admission and discharge, and incidence of
      subarachnoid hemorrhage, epidural hematoma, contusion, or skull fractures between
      the operated and nonoperated groups. All patients in the operated group had
      subdural hematoma compared with 40.8% in the nonoperated group (P = 0.07). All
      operated patients showed symptoms of neurologic worsening after initial head CT,
      compared with 2.7% in the nonoperated group (P < 0.001). Moreover, patients who
      showed neurologic worsening were more likely to show increased intracranial
      bleeding on repeat head CT, whereas patients who did not show neurologic
      worsening were more likely to show decreased or stable intracranial bleeding (P =
      0.04). CONCLUSIONS: Routine repeat head CT in patients with complicated mild TBI
      is very low yield to predict need for delayed surgical intervention. Instead,
      serial neurologic examination and observation over the first 8 hours after the
      injury is recommended. A second CT scan should be obtained only in patients who
      have neurologic worsening.

PMID- 28502690
TI  - The Clinical Effect of Postoperative Hyperbaric Oxygen Therapy on Idiopathic
      Normal Pressure Hydrocephalus: A Retrospective and Comparative Analysis of 61
      Patients with Ventriculoperitoneal Shunt.
AB  - OBJECTIVE: The aim of the study was to examine the clinical effect of
      postoperative hyperbaric oxygen (HBO) therapy on symptoms and signs in the
      ventriculoperitoneal (VP) shunt insertion treatment of idiopathic normal pressure
      hydrocephalus (iNPH). METHODS: We conducted a retrospective analysis of 61
      patients treated at our institution for iNPH since 2007. Patients were stratified
      into 2 groups according to undergoing pure VP shunt with gravitational valves
      (group 1) or combined with postoperative HBO therapy (group 2). Clinical
      improvements as well as complications were compared between the 2 groups.
      RESULTS: There was no significant difference between the 2 groups regarding age,
      sexual proportion, body mass index, education years, and the average Normal
      Pressure Hydrocephalus Scale score before the surgery, as well as the
      complication rate after the surgery (P > 0.05). On average, the total Normal
      Pressure Hydrocephalus Scale scores were both increased in the 2 groups at 1, 3,
      and 6 months after shunting, with no significant differences (P > 0.05). However,
      group 2 tended to increase more compared with group 1, especially 6 months later
      after shunting. The increase of cognitive functions was more significant in group
      2 (P < 0.05). CONCLUSIONS: HBO therapy combined with VP shunt is expected to
      improve the effect of iNPH treatment, especially for cognitive performance.

PMID- 28502691
TI  - Long-Term Seizure, Quality of Life, Depression, and Verbal Memory Outcomes in a
      Controlled Mesial Temporal Lobe Epilepsy Surgical Series Using Portuguese
      Validated Instruments.
AB  - OBJECTIVE: We aimed to evaluate long-term surgical outcomes in patients treated
      for mesial temporal lobe epilepsy compared with a similar group of patients who
      underwent a preoperative evaluation. METHODS: Patient interviews were conducted
      by an independent neuropsychologist and included a sociodemographic questionnaire
      and validated versions of the Beck Depression Inventory-II, Adverse Events
      Profile, Quality of Life in Epilepsy-31, and Rey Auditory Verbal Learning Test.
      RESULTS: Seventy-one patients who underwent surgery and 20 who underwent mesial
      temporal lobe epilepsy preoperative evaluations were interviewed. After an 81
      month mean postoperative follow-up, 44% of the surgical patients achieved
      complete seizure relief according to the Engel classification and 68% according
      to the International League Against Epilepsy classification. The surgical group
      had a significantly lower prevalence of depression (P = 0.002) and drug-related
      adverse effects (P = 0.002). Improvement on unemployment (P = 0.02) was achieved
      but not on driving or education. Delayed verbal memory recall was impaired in 76%
      of the surgical and 65% of the control cases (P = 0.32). Regarding the Quality of
      Life in Epilepsy-31, the operated patients scored higher in their total score
      (mean, 75.44 vs. mean, 60.08; P < 0.001) and in all but the cognitive functioning
      domain irrespective of the follow-up length. Seizure control, Beck Depression
      Score, and Adverse Events Profile severity explained 73% of the variance in the
      surgical group quality of life. CONCLUSIONS: Our study found that, although
      surgical treatment was effective, its impact on social indicators was modest.
      Moreover, the self-reported quality of life relied not only on seizure control
      but also on depressive symptoms and antiepileptic drug burden.

PMID- 28502693
TI  - Prolonged Blood-Brain Barrier Disruption Following Laser Interstitial Ablation in
      Epilepsy: A Case Series with a Case Report of Postablation Optic Neuritis.
AB  - OBJECTIVE: Laser interstitial thermal therapy has become increasingly popular for
      targeting epileptic foci in a minimally invasive fashion. Despite its use in
      >1000 patients, the long-term effects of photothermal injury on brain physiology
      remain poorly understood. METHODS: We prospectively followed clinical and
      radiographic courses of 13 patients undergoing laser ablation for focal epilepsy
      by the senior author (N.T.). Only patients with nonenhancing lesions and patients
      who had a delayed postoperative magnetic resonance imaging (MRI) scan with
      gadolinium administration approximately 6 months after ablation were considered.
      Volumetric estimates of the amount of enhancement immediately after ablation and
      on the delayed MRI scan were made. RESULTS: Median interval between surgery and
      delayed postoperative MRI scan was 6 months (range, 5-8 months). In 12 of 13
      cases, persistent enhancement was seen, consistent with prolonged blood-brain
      barrier dysfunction. Enhancement, when present, was 9%-67% (mean 30%). There was
      no correlation between the time from surgery and the relative percentage of
      postoperative enhancement on MRI. The blood-brain barrier remained compromised to
      gadolinium contrast for up to 8 months after thermal therapy. There were no
      adverse events from surgical intervention; however, 1 patient developed delayed
      optic neuritis. CONCLUSIONS: Prolonged incompetence of the blood-brain barrier
      produced by thermal ablation may provide a path for delivery of macromolecules
      into perilesional tissue, which could be exploited for therapeutic benefit, but
      rarely it may result in autoimmune central nervous system inflammatory
      conditions.

PMID- 28502694
TI  - Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without
      enzalutamide in men with metastatic castration resistant prostate cancer.
AB  - BACKGROUND: Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway
      activation is common in metastatic castration resistant prostate cancer (mCRPC).
      Buparlisib is an oral, pan-class I PI3 kinase inhibitor. METHODS: This was a
      multisite single arm phase II trial of buparlisib 100 mg +/- enzalutamide daily
      in men with mCRPC whose disease progressed on or who were not candidates for
      docetaxel. The primary end-point was the rate of radiographic/clinical
      progression-free survival (PFS) at 6 months. RESULTS: Thirty men were accrued:
      67% post-docetaxel; median prostate specific antigen (PSA) was 70 ng/dl, 83% had
      >=4 prior therapies for mCRPC; 43% received concurrent enzalutamide. The final 6
      month PFS rate was estimated to be 10% (95% confidence interval 2.5-23.6%).
      Median PFS was 1.9 months and was 3.5 months with concurrent enzalutamide. Median
      overall survival was 10.6 months. Concurrent enzalutamide led to a five-fold
      reduction in buparlisib concentrations. PSA declines were observed in 23%; no
      patients achieved a >=50% decline, and no radiographic responses were observed.
      Severe adverse events occurred in four men including respiratory infection and
      multi-organ failure, urinary tract obstruction, confusion and one seizure in the
      setting of a new central nervous system (CNS) metastasis. Grade III adverse
      events were seen in 43% of patients; common toxicities included grade I-II weight
      loss, diarrhoea, nausea, fatigue, anorexia, rash, hyperglycemia and anxiety/mood
      disorders. CONCLUSIONS: Buparlisib did not demonstrate significant activity in
      men with mCRPC, suggesting that PI3K inhibition is not sufficient to reverse
      resistant mCRPC progression. Future studies of PI3K pathway inhibitors with
      concurrent enzalutamide should develop optimal dosing and focus on selected
      patients more likely to benefit.

PMID- 28502695
TI  - Selective Activation of Estrogen Receptor alpha Activation Function-1 Is
      Sufficient to Prevent Obesity, Steatosis, and Insulin Resistance in Mouse.
AB  - Estrogen receptor alpha (ERalpha) regulates gene transcription through two
      activation functions (ERalpha-AF1 and ERalpha-AF2). We recently found that the
      protection conferred by 17beta-estradiol against obesity and insulin resistance
      requires ERalpha-AF2 but not ERalpha-AF1. However, the interplay between the two
      ERalpha-AFs is poorly understood in vivo and the metabolic influence of a
      specific ERalpha-AF1 action remains to be explored. To this end, wild-type,
      ERalpha-deficient, or ERalpha-AF1-deficient ovariectomized female mice were fed a
      high-fat diet and concomitantly administered with vehicle or tamoxifen, a
      selective ER modulator that acts as a ERalpha-AF1 agonist/ERalpha-AF2 antagonist.
      In ovariectomized wild-type mice, tamoxifen significantly reduced food intake and
      totally prevented adiposity, insulin resistance, and steatosis. These effects
      were abolished in ERalpha-deficient and ERalpha-AF1-deficient mice, revealing the
      specific role of ERalpha-AF1 activation. Finally, hepatic gene expression changes
      elicited by tamoxifen in wild-type mice were abrogated in ERalpha-AF1-deficient
      mice. The combination of pharmacologic and transgenic approaches thus indicates
      that selective ERalpha-AF1 activation by tamoxifen is sufficient to elicit
      metabolic protection, contrasting with the specific requirement of ERalpha-AF2 in
      the metabolic actions of 17beta-estradiol. This redundancy in the ability of the
      two ERalpha-AFs to separately mediate metabolic prevention strikingly contrasts
      with the contribution of both ERalpha-AFs in breast cancer proliferation,
      shedding new light on the therapeutic potential of selective ER modulation.

PMID- 28502697
TI  - Impact of high-flux haemodialysis on the probability of target attainment for
      oral amoxicillin/clavulanic acid combination therapy.
AB  - Clearance of small molecules such as amoxicillin and clavulanic acid is expected
      to increase during high-flux haemodialysis, which may result in lower
      concentrations and thus reduced efficacy. To date, clearance of
      amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely
      unexplored. Using published pharmacokinetic parameters, a two-compartment model
      with first-order input was simulated to investigate the impact of high-flux
      haemodialysis on the probability of target attainment (PTA) of orally
      administered AMC combination therapy. The following
      pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For
      amoxicillin, the time that the free concentration remains above the minimum
      inhibitory concentration (MIC) of >=50% of the dosing period (>=50%fT>MIC) was
      used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of
      >=45% of the dosing period (>=45%fT>0.1 mg/L) was used. Dialysis clearance
      reported in low-flux haemodialysis for both compounds was doubled to represent
      the likely clearance during high-flux haemodialysis. Monte Carlo simulations were
      performed to produce concentration-time profiles over 10 days in 1000 virtual
      patients. Seven different regimens commonly seen in clinical practice were
      explored. When AMC was dosed twice daily, the PTA was mostly >=90% for both
      compounds regardless of when haemodialysis commenced. When administered once
      daily, the PTA was 20-30% for clavulanic acid and >=90% for amoxicillin. The
      simulations suggest that once-daily orally administered AMC in patients receiving
      high-flux haemodialysis may result in insufficient concentrations of clavulanic
      acid to effectively treat infections, especially on days when haemodialysis
      occurs.

PMID- 28502696
TI  - Reverse zoonotic transmission of community-associated MRSA ST1-IV to a dairy cow.

PMID- 28502698
TI  - Effectiveness of a fine motor skills rehabilitation program on upper limb
      disability, manual dexterity, pinch strength, range of fingers motion,
      performance in activities of daily living, functional independency, and general
      self-efficacy in hand osteoarthritis: A randomized clinical trial.
AB  - STUDY DESIGN: A randomized clinical trial. INTRODUCTION: Rehabilitation
      treatments for improving fine motor skills (FMS) in hand osteoarthritis (HOA)
      have not been well explored yet. PURPOSE OF THE STUDY: To assess the
      effectiveness of a rehabilitation program on upper limb disability, independence
      of activities of daily living (ADLs), fine motor abilities, functional
      independency, and general self-efficacy in older adults with HOA. METHODS: About
      45 adults (74-86 years) with HOA were assigned to an experimental group for
      completing an FMS intervention or a control group receiving conventional
      occupational therapy. Both interventions were performed 3 times/wk, 45 minutes
      each session, during 8 weeks. Upper limb disability, performance in ADLs, pinch
      strength, manual dexterity, range of fingers motion, functional independency, and
      general self-efficacy were assessed at baseline, immediately after treatment, and
      after 2 months of follow-up. RESULTS: FMS group showed significant improvements
      with a small effect size on manual dexterity (P <= .034; d >= 0.48) and a
      moderate-high effect on range of index (P <= .018; d >= 0.58) and thumb (P <=
      .027; d >= 0.39) motion. The control group showed a significant worse range of
      motion over time in some joints at the index (P <= .037; d >= 0.36) finger and
      thumb (P <= .017; d >= 0.55). CONCLUSIONS: A rehabilitation intervention for FMS
      may improve manual dexterity and range of fingers motion in HOA, but its effects
      on upper limb disability, performance in ADLs, pinch strength, functionality, and
      self-efficacy remain uncertain. Specific interventions of the hand are needed to
      prevent a worsening in range of finger motion. LEVEL OF EVIDENCE: 1b.

PMID- 28502692
TI  - What Factors Determine Treatment Outcome in Aneurysmal Subarachnoid Hemorrhage in
      the Modern Era? A Post Hoc STASH Analysis.
AB  - BACKGROUND: The management of aneurysmal subarachnoid hemorrhage (aSAH) has
      changed dramatically in the last few decades with the publication of a few major
      studies, including ISAT (International Subarachnoid Aneurysm Trial, the
      International Cooperative Study on the Timing of Aneurysm Surgery Study). The aim
      of this study is to analyze the outcome of patients with aSAH based on a
      contemporary series, identify the risk factors for poor outcome, and focus on
      patients with good-grade aSAH (to match the ISAT cohort). METHODS: Baseline
      demographic and outcome data (modified Rankin Scale) were available for the 803
      patients recruited from the STASH (Simvastatin in Aneurysmal Subarachnoid
      Haemorrhage) trial for post hoc analysis, using a chi2 test or 2-sample t test.
      Logistic regression analysis was performed to assess the risk factors for poor
      outcome at 6 months. Propensity matched analysis comparing coiling and clipping,
      and subgroup analysis of good-grade patients (World Federation of Neurosurgical
      Societies grade I-II) were also performed. RESULTS: Logistic regression analysis
      showed that the treatment modality (i.e., coiling or clipping) was not associated
      with poor outcome at 6 months (P = 0.839). The risk factors associated with poor
      outcome at 6 months were poor admission World Federation of Neurosurgical
      Societies grade (P < 0.0001), Fisher grade on initial computed tomography scan (P
      = 0.013), and the development of delayed cerebral ischemia (P < 0.0001). Subgroup
      analysis for good-grade patients only showed that 82% of patients after coiling
      and 78% of patients after clipping were classed as good outcome at 6 months (P =
      0.181). CONCLUSIONS: In the current era of aSAH management, apart from patients'
      admission status, SAH blood load and the development of delayed cerebral
      ischemia, treatment modality with either coiling or clipping was not associated
      with poor outcome difference at 6 months.

PMID- 28502701
TI  - FastPCR: An in silico tool for fast primer and probe design and advanced sequence
      analysis.
AB  - Polymerase chain reaction (PCR) is one of the most important laboratory
      techniques used in molecular biology, genetics and molecular diagnostics. The
      success of a PCR-based method largely depends on the correct nucleic acid
      sequence analysis in silico prior to a wet-bench experiment. Here, we report the
      development of an online Java-based software for virtual PCR on linear or
      circular DNA templates and multiple primer or probe search from large or small
      databases. Primer or probe sensitivity and specificity are predicted by searching
      a database to find sequences with an optimal number of mismatches, similarity and
      stability. The software determines primer location, orientation, efficiency of
      binding and calculates primer melting temperatures for standard and degenerate
      oligonucleotides. The software is suitable for batch file processing, which is
      essential for automation when working with large amounts of data. The online Java
      software is available for download at http://primerdigital.com/tools/pcr.html.
      Accession numbers for the sequences resulting from this study: EU140956 EU177767
      EU867815 EU882730 FJ975775-FJ975780 HM481419 HM481420 KC686837-KC686839 KM262797.

PMID- 28502699
TI  - Supraspinatus tendon micromorphology in individuals with subacromial pain
      syndrome.
AB  - STUDY DESIGN: Cross-sectional cohort. INTRODUCTION: Tendon collagen organization
      can be estimated by peak spatial frequency radius (PSFR) on ultrasound images.
      Characterizing PSFR can define the contribution of collagen disruption to
      shoulder symptoms. PURPOSE OF THE STUDY: The purpose of this was to characterize
      the (1) supraspinatus tendon PSFR in participants with subacromial pain syndrome
      (SPS) and healthy controls; (2) PSFR between participants grouped on a tendon
      visual quality score; and (3) relationship between PSFR with patient-reported
      pain, function, and shoulder strength. METHODS: Participants with SPS (n = 20)
      and age, sex, and arm-dominance-matched healthy controls (n = 20) completed
      strength testing in scaption and external rotation, and patient-reported pain,
      and functional outcomes. Supraspinatus tendon ultrasound images were acquired,
      and PSFR was calculated for a region of interest 15 mm medial to the
      supraspinatus footprint. PSFR was compared between groups using an independent t
      test and an analysis of variance to compare between 3 groups for visually
      qualitatively rated tendon abnormalities. Relationships between PSFR with pain,
      function, and strength were assessed using Pearson correlation coefficient.
      RESULTS: Supraspinatus tendon PSFR was not different between groups (P = .190) or
      tendon qualitative ratings (P = .556). No relationship was found between PSFR and
      pain, functional loss, and strength (P > .05). CONCLUSIONS: Collagen disruption
      (PSFR) measured via ultrasound images of the supraspinatus tendon was not
      different between participants with SPS or in those with visually rated tendon
      defects. PSFR is not related to shoulder pain, function, and strength, suggesting
      that supraspinatus tendon collagen disorganization may not be a contributing
      factor to shoulder SPS. However, collagen disruption may not be isolated to a
      single region of interest. LEVEL OF EVIDENCE: 3b: case-control study.

PMID- 28502700
TI  - Fetal Alcohol Spectrum Disorders (FASD) and competency to stand trial (CST):
      Suggestions for a 'best practices' approach to forensic evaluation.
AB  - Fetal Alcohol Spectrum Disorders (FASD), an umbrella term for neurodevelopmental
      conditions caused by prenatal alcohol exposure, is overrepresented in the U.S.
      juvenile and adult criminal justice systems. The brain damage in FASD manifests
      in a combination of cognitive and adaptive impairments that potentially reduce
      ability to function adequately during the criminal justice process, including
      capacity to stand trial (CST). Despite the high risk of arrest and conviction in
      this population, relatively little research guides CST assessment for defendants
      who have or may have FASD. Therefore, the purpose of this article is to describe
      how FASD may affect CST and suggest ways forensic professionals might modify
      assessment protocols to address possible effects of FASD-associated impairments
      on adjudicative capacity.

PMID- 28502702
TI  - Deep sequencing reveals complex mechanisms of microRNA regulation during retinoic
      acid-induced neuronal differentiation of mesenchymal stem cells.
AB  - Retinoic acid (RA) has an important role in nervous system development; exogenous
      RA could induce stem cells towards neural lineage cells. However, the miRNA
      regulation mechanism and biological process of this induction require further
      exploration. In this study, using high-throughput sequencing results, we
      evaluated the microRNA profiles of neurally differentiated adipose-derived
      mesenchymal stem cells (ASCs), summarized several crucial microRNAs that
      profoundly contributed to the differentiation process, and speculated that
      several miRNAs were likely to mimic RA or other factors to induce the neuronal
      differentiation of stem cells. The GO terms and KEGG PATHWAY in the DAVID tool
      were used to elucidate the biological process of RA induction. Finally, we
      described a network for clarifying the relationship among the miRNAs, target
      genes and signaling pathways. These findings will be beneficial for understanding
      the induction mechanism and supporting the application of RA in stem cell
      transformation.

PMID- 28502703
TI  - Cell death induced by mitochondrial complex I inhibition is mediated by Iron
      Regulatory Protein 1.
AB  - Mitochondrial dysfunction and oxidative damage, often accompanied by elevated
      intracellular iron levels, are pathophysiological features in a number of
      neurodegenerative processes. The question arises as to whether iron
      dyshomeostasis is a consequence of mitochondrial dysfunction. Here we have
      evaluated the role of Iron Regulatory Protein 1 (IRP1) in the death of SH-SY5Y
      dopaminergic neuroblastoma cells subjected to mitochondria complex I inhibition.
      We found that complex I inhibition was associated with increased levels of
      transferrin receptor 1 (TfR1) and iron uptake transporter divalent metal
      transporter 1 (DMT1), and decreased levels of iron efflux transporter Ferroportin
      1 (FPN1), together with increased 55Fe uptake activity and an increased
      cytoplasmic labile iron pool. Complex I inhibition also resulted in increased
      oxidative modifications and increased cysteine oxidation that were inhibited by
      the iron chelators desferoxamine, M30 and Q1. Silencing of IRP1 abolished the
      rotenone-induced increase in 55Fe uptake activity and it protected cells from
      death induced by complex I inhibition. IRP1 knockdown cells presented higher
      ferritin levels, a lower iron labile pool, increased resistance to cysteine
      oxidation and decreased oxidative modifications. These results support the
      concept that IRP1 is an oxidative stress biosensor that mediates iron
      accumulation and cell death when deregulated by mitochondrial dysfunction. IRP1
      activation, secondary to mitochondrial dysfunction, may underlie the events
      leading to iron dyshomeostasis and neuronal death observed in neurodegenerative
      disorders with an iron accumulation component.

PMID- 28502704
TI  - Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of
      autism.
AB  - BACKGROUND: Protein O-linked-beta-N-acetyl glucosamine (O-GlcNAc) is a post
      translational modification to Ser/Thr residues that integrates energy supply with
      demand. Abnormal O-GlcNAc patterning is evident in several neurological disease
      states including epilepsy, Alzheimer's disease and autism spectrum disorder
      (ASD). A potential treatment option for these disorders includes the high-fat,
      low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine
      whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model
      of ASD. METHODS: Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a
      chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. Following these
      diets, brain (prefrontal cortex) and liver were examined for gene expression
      levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as
      indicators of energy status. RESULTS: The KD reduced global O-GlcNAc in the
      livers of all animals (p<0.05). Reductions were likely mediated by lower protein
      levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). In
      contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet
      OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals
      (p<0.05). CONCLUSIONS: The KD has tissue specific impacts on O-GlcNAc. Although
      levels of O-GlcNAc play an important role in neurodevelopment, levels of this
      modification in the juvenile mouse brain were stable with the KD despite large
      fluctuations in energy status. This suggests that it is unlikely that the KD
      exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related
      pathways.

PMID- 28502706
TI  - Reprogramming of central carbon metabolism in cancer stem cells.
AB  - Cancer metabolism has been studied for years and adopted in the clinic for
      monitoring disease progression and therapy response. Despite our growing
      knowledge of a distinctly altered metabolic behavior in cancer, drugs targeting
      cancer metabolism have remained less than promising. Recent efforts in cancer
      stem cell (CSC) biology suggest that a subpopulation of tumor-initiating cells
      within the tumor bulk represents the root of tumor recurrence and therapy
      resistance. In recent years, metabolic phenotype of CSCs of various tumor types
      has been identified. This breakthrough has shed light on the underlying mechanism
      by which CSCs maintain stemness, confer resistance to therapies and initiate
      tumor relapse. The distinct metabolic characteristics of CSCs compared to non
      CSCs provide an opportunity to target CSCs more specifically and have become a
      major focus in cancer research in recent years with substantial efforts conducted
      towards discovering clinical targets. This perspective article summarizes the
      current knowledge of CSC metabolism in carcinogenesis and highlights the
      potential of targeting CSC metabolism for therapy.

PMID- 28502705
TI  - BAG-1M co-activates BACE1 transcription through NF-kappaB and accelerates Abeta
      production and memory deficit in Alzheimer's disease mouse model.
AB  - Accumulation of amyloid beta protein (Abeta)-containing neuritic plaques in the
      brain is a neuropathological feature of Alzheimer's disease (AD). The beta-site
      APP-cleaving enzyme 1 (BACE1) is essential for Abeta generation and dysregulation
      of BACE1 expression may lead to AD pathogenesis. Bcl-2-associated athanogen 1M
      (BAG-1M), initially identified as an anti-apoptotic protein, has also been found
      to be highly expressed in the same neurons that contain intracellular amyloid in
      the hippocampus of AD patient. In this report, we found that over-expression of
      BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and
      Abeta production by up-regulating BACE1 gene transcription. The regulation of
      BACE1 transcription by BAG-1M was dependent on NF-kappaB, as BAG-1M complexes NF
      kappaB at the promoter of BACE1 gene and co-activates NF-kappaB-facilitated BACE1
      transcription. Moreover, expression of BAG-1M by lentiviral vector in the
      hippocampus of AD transgenic model mice promotes Abeta generation and formation
      of neuritic plaque, and subsequently accelerates memory deficits of the mice.
      These results provide evidence for an emerging role of BAG-1M in the regulation
      of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-kappaB
      complex may provide a mechanism for inhibiting Abeta production and plaque
      formation.

PMID- 28502707
TI  - Surgical Innovation in Sarcoma Surgery.
AB  - The field of orthopaedic oncology relies on innovative techniques to resect and
      reconstruct a bone or soft tissue tumour. This article reviews some of the most
      recent and important innovations in the field, including biological and implant
      reconstructions, together with computer-assisted surgery. It also looks at
      innovations in other fields of oncology to assess the impact and change that has
      been required by surgeons; topics including surgical margins, preoperative
      radiotherapy and future advances are discussed.

PMID- 28502708
TI  - 2017 HRS expert consensus statement on magnetic resonance imaging and radiation
      exposure in patients with cardiovascular implantable electronic devices.

PMID- 28502709
TI  - Organizational Innovation of Apical Actin Filaments Drives Rapid Pollen Tube
      Growth and Turning.
AB  - Polarized tip growth is a fundamental cellular process in many eukaryotes. In
      this study, we examined the dynamic restructuring of the actin cytoskeleton and
      its relationship to vesicle transport during pollen tip growth in Arabidopsis. We
      found that actin filaments originating from the apical membrane form a
      specialized structure consisting of longitudinally aligned actin bundles at the
      cortex and inner cytoplasmic filaments with a distinct distribution. Using actin
      based pharmacological treatments and genetic mutants in combination with FRAP
      (fluorescence recovery after photobleaching) technology to visualize the
      transport of vesicles within the growth domain of pollen tubes, we demonstrated
      that cortical actin filaments facilitate tip-ward vesicle transport. We also
      discovered that the inner apical actin filaments prevent backward movement of
      vesicles, thus ensuring that sufficient vesicles accumulate at the pollen tube
      tip to support the rapid growth of the pollen tube. The combinatorial effect of
      cortical and internal apical actin filaments perfectly explains the generation of
      the inverted "V" cone-shaped vesicle distribution pattern at the pollen tube tip.
      When pollen tubes turn, apical actin filaments at the facing side undergo
      depolymerization and repolymerization to reorient the apical actin structure
      toward the new growth direction. This actin restructuring precedes vesicle
      accumulation and changes in tube morphology. Thus, our study provides new
      insights into the functional relationship between actin dynamics and vesicle
      transport during rapid and directional pollen tube growth.

PMID- 28502710
TI  - Graduating Pediatric Residents Entering the Hospital Medicine Workforce, 2006
      2015.
AB  - OBJECTIVE: In October 2016, the American Board of Medical Specialties approved
      the petition for pediatric hospital medicine (PHM) to become the newest pediatric
      subspecialty. Knowledge about residents entering the PHM workforce is needed to
      inform certification and fellowship accreditation. This study describes the
      characteristics of graduating pediatric residents with PHM positions and
      identifies factors associated with postresidency position choices. METHODS: We
      analyzed data from the American Academy of Pediatrics Annual Survey of Graduating
      Residents, 2006-2015. Chi-square tests were used to compare responses between
      residents entering PHM to those entering subspecialty fellowships, and to compare
      residents entering PHM at community and tertiary-care hospitals. We used
      multivariable logistic regression to identify associations between resident and
      training characteristics and position choices. RESULTS: A total of 5969
      respondents completed the survey (60.6% response rate); 593 (10.3%) reported that
      they were entering PHM and 1954 (33.9%) reported subspecialty fellowships. Of
      residents entering PHM, 345 (60.7%) reported positions at tertiary-care hospitals
      and 194 (34.2%) reported positions at community hospitals. Seventy percent of
      residents entering PHM envisioned long-term PHM careers, with PHM career goals
      more frequently reported among residents entering community hospitalist positions
      (P < .01). In multivariable analysis, residents entering PHM were significantly
      more likely to be female, to have children, to report that family factors limited
      their job selection, and to have higher levels of educational debt than residents
      entering fellowships. CONCLUSIONS: Factors associated with postresidency PHM
      positions, including substantial educational debt and sociodemographic
      characteristics, may influence the development of the field as the specialty
      pursues fellowship accreditation.

PMID- 28502711
TI  - An improved method to measure lipase activity in aqueous media.
AB  - An improved method based on the p-nitrophenyl long chain esters method is
      proposed for measuring lipase hydrolytic activity in aqueous media. Using
      ethylene glycol as co-solvent for hydrophobic p-nitrophenyl substrates in aqueous
      buffer, lipase activity is measured by following the release of p-nitrophenol.
      This fast and easy to handle method improves the solubility of both substrate and
      product, and also the stability of the substrate. It avoids the use of solvents
      such as ethanol or propanol, permits the comparison of all the p-nitrophenol acyl
      ester substrates and allows the influence of ions like Ca+2 to be studied, while
      avoiding turbidity in the reaction medium.

PMID- 28502712
TI  - Ligation-mediated PCR with a back-to-back adapter reduces amplification bias
      resulting from variations in GC content.
AB  - Ligation-mediated polymerase chain reaction (LM-PCR) is a common technique for
      amplification of a pool of DNA fragments. Here, a double-stranded oligonucleotide
      consisting of two primer sequences in back-to-back orientation was designed as an
      adapter for LM-PCR. When DNA fragments were ligated with this adapter, the
      fragments were sandwiched between two adapters in random orientations. In the
      ensuing PCR, ligation products linked at each end to an opposite side of the
      adapter, i.e. to a distinct primer sequence, were preferentially amplified
      compared with products linked at each end to an identical primer sequence. The
      use of this adapter in LM-PCR reduced the impairment of PCR by substrate DNA with
      a high GC content, compared with the use of traditional LM-PCR adapters. This
      result suggested that our method has the potential to contribute to reduction of
      the amplification bias that is caused by an intrinsic property of the sequence
      context in substrate DNA. A DNA preparation obtained from a chromatin
      immunoprecipitation assay using pulldown of a specific form of histone H3 was
      successfully amplified using the modified LM-PCR, and the amplified products
      could be used as probes in a fluorescence in situ hybridization analysis.

PMID- 28502713
TI  - An autopsy case of fatal acute peritonitis complicated by illegal acupuncture
      therapy.
AB  - Acupuncture is an alternative medical therapy and widely practiced in Northeast
      Asia. Although it is known as a safe procedure, complications including
      infection, pneumothorax, hemorrhage, and cardiac tamponade have been reported.
      The authors present a rare case of fatal acute peritonitis due to penetration of
      acupuncture needles directly into the abdominal and pelvic cavity. The victim was
      a 55-year-old woman who had a recent history of chemo-radiotherapy due to breast
      cancer. She was collapsed three days after receiving acupuncture. She had
      symptoms of fever and chilling sensation, general myalgia, and vomiting during
      three days. The autopsy revealed several needle marks in the lower abdomen and
      180ml of bloody exudate in the abdominal cavity. There was no visible intestinal
      perforation, but hemorrhagic foci in the mesentery and paracolic area of sigmoid
      colon were noted. The deepest portion was 13.5cm from the needle marks on the
      abdominal skin. The practitioner had not a Chinese medical license. He was
      accused of illegal medical practice and manslaughter. Acute peritonitis
      associated with acupuncture might be caused by inadequate sterilization of skin
      and needle itself and/or direct mesentery injury.

PMID- 28502714
TI  - Why is it so difficult to determine the yield of indoor cannabis plantations? A
      case study from the Netherlands.
AB  - Together, the Netherlands and Belgium are the largest indoor cannabis producing
      countries in Europe. In both countries, legal prosecution procedure of convicted
      illicit cannabis growers usually includes recovery of the profits gained.
      However, it is not easy to make a reliable estimation of the latter profits, due
      to the wide range of factors that determine indoor cannabis yields and eventual
      selling prices. In the Netherlands, since 2005, a reference model is used that
      assumes a constant yield (g) per plant for a given indoor cannabis plant density.
      Later, in 2011, a new model was developed in Belgium for yield estimation of
      Belgian indoor cannabis plantations that assumes a constant yield per m2 of
      growth surface, provided that a number of growth conditions are met. Indoor
      cannabis plantations in the Netherlands and Belgium share similar technical
      characteristics. As a result, for indoor cannabis plantations in both countries,
      both aforementioned yield estimation models should yield similar yield
      estimations. By means of a real-case study from the Netherlands, we show that the
      reliability of both models is hampered by a number of flaws and unmet
      preconditions. The Dutch model is based on a regression equation that makes use
      of ill-defined plant development stages, assumes a linear plant growth, does not
      discriminate between different plantation size categories and does not include
      other important yield determining factors (such as fertilization). The Belgian
      model addresses some of the latter shortcomings, but its applicability is
      constrained by a number of pre-conditions including plantation size between 50
      and 1000 plants; cultivation in individual pots with peat soil; 600W (electrical
      power) assimilation lamps; constant temperature between 20 degrees C and 30
      degrees C; adequate fertilizer application and plants unaffected by pests and
      diseases. Judiciary in both the Netherlands and Belgium require robust indoor
      cannabis yield models for adequate legal prosecution of illicit indoor cannabis
      growth operations. To that aim, the current models should be optimized whereas
      the validity of their application should be examined case by case.

PMID- 28502715
TI  - Identification of mature peptides from pban and capa genes of the moths Heliothis
      peltigera and Spodoptera littoralis.
AB  - By transcriptome analysis, we identified PBAN and CAPA precursors in the moths
      Spodoptera littoralis and Heliothis peltigera which are among the most damaging
      pests of agriculture in tropical and subtropical Africa as well as in
      Mediterranean countries. A combination of mass spectrometry and
      immunocytochemistry was used to identify mature peptides processed from these
      precursors and to reveal their spatial distribution in the CNS. We found that the
      sites of expression of pban genes, the structure of PBAN precursors and the
      processed neuropeptides are very similar in noctuid moths. The sequence of the
      diapause hormone (DH; tryptopyrokinin following the signal peptide), however,
      contains two N-terminal amino acids more than expected from comparison with
      already published sequences of related species. Capa genes of S. littoralis and
      H. peltigera encode, in addition to periviscerokinins, a tryptopyrokinin showing
      sequence similarity with DH, which is the tryptopyrokinin of the pban gene. CAPA
      peptides, which were not known from any noctuid moth so far, are produced in
      cells of abdominal ganglia. The shape of the release sites of these hormones in
      H. peltigera represents an exceptionally derived trait state and does not
      resemble the well-structured abdominal perisympathetic organs which are known
      from many other insects. Instead, axons of CAPA cells extensively ramify within
      the ventral diaphragm. The novel information regarding the sequences of all
      mature peptides derived from pban and capa genes of H. peltigera and S.
      littoralis now enables a detailed analysis of the bioactivity and species
      specificity of the native peptides, especially those from the hitherto unknown
      capa genes, and to explore their interactions with PBAN/DH receptors.

PMID- 28502716
TI  - Neuropeptides predicted from the transcriptome analysis of the gray garden slug
      Deroceras reticulatum.
AB  - The gray garden slug, Deroceras reticulatum (Gastropoda: Pulmonata), is one of
      the most common terrestrial molluscs. Research for this slug has focused mainly
      on its ecology, biology, and management due to the severe damage it causes on a
      wide range of vegetables and field crops. However, little is known about
      neuropeptides and hormonal signalings. This study, therefore, aimed to establish
      the transcriptome of D. reticulatum and to identify a comprehensive repertoire of
      neuropeptides in this slug. Illumina high-throughput sequencing of the whole body
      transcriptome of D. reticulatum generated a total of 5.9 billion raw paired-end
      reads. De novo assembly by Trinity resulted in 143,575 transcripts and further
      filtration selected 120,553 unigenes. Gene Ontology (GO) terms were assigned to
      30,588 unigenes, composed of biological processes (36.9%), cellular components
      (30.2%) and molecular functions (32.9%). Functional annotation by BLASTx revealed
      39,987 unigenes with hits, which were further categorized into important
      functional groups based on sequence abundance. Neuropeptides, ion channels,
      ribosomal proteins, G protein-coupled receptors, detoxification, immunity and
      cytoskeleton-related sequences were dominant among the transcripts. BLAST
      searches and PCR amplification were used to identify 65 putative neuropeptide
      precursor genes from the D. reticulatum transcriptome, which include achatin,
      AKH, allatostatin A, B and C, allatotropin, APGWamide, CCAP, cerebrin,
      conopressin, cysteine-knot protein hormones (bursicon alpha/beta and GPA2/GPB5),
      elevenin, FCAP, FFamide, FVamide (enterin, fulicin, MIP and PRQFVamide), GGNG,
      GnRH, insulin, NdWFamide, NKY, PKYMDT, PRXamide (myomodulin, pleurin and sCAP),
      RFamide (CCK/SK, FMRFamide, FxRIamide, LFRFamide, luqin and NPF), and tachykinin.
      Over 330 putative peptides were encoded by these precursors. Comparative analysis
      among different molluscan species clearly revealed that, while D. reticulatum
      neuropeptide sequences are conserved in Mollusca, there are also some unique
      features distinct from other members of this species. This is the first
      transcriptome-wide report of neuropeptides in terrestrial slugs. Our results
      provide comprehensive transcriptome data of the gray garden slug, with a more
      detailed focus on the rich repertoire of putative neuropeptide sequences, laying
      the foundation for molecular studies in this terrestrial slug pest.

PMID- 28502717
TI  - Preferential accumulation of gold nanorods into human skin hair follicles: Effect
      of nanoparticle surface chemistry.
AB  - HYPOTHESIS: Gold nanoparticles (GNP) are considered an ideal model to help
      understanding the nano-skin interface. The surface functionality of gold nanorods
      (GNR) is expected to influence the uptake of nanoparticles into specific targets
      of skin such as hair follicles or dermis. Hence, it should be possible to modify
      the surface chemistry of GNP to achieve more targeted and safe skin therapy.
      EXPERIMENTS: GNR functionalized with various surface ligands (neutral, anionic,
      cationic, and hydrophobic) were evaluated for their accumulation into hair
      follicles of human skin sheets using ex-vivo setup. The extent of GNR
      accumulation into hair follicles and other skin compartments was quantified by
      inductively coupled plasma-optical emission spectroscopy (ICP-OES), and their
      spatial distribution through skin layers was investigated by laser ablation
      inductively coupled plasma-mass spectroscopy (LA-ICP-MS). RESULTS: The lipophilic
      properties of sebum-rich hair follicles enhanced the accumulation of hydrophobic
      polystyrene (PS)-GNR into hair follicles (~13% of the total applied dose), while
      neutral polyethylene glycol (PEG)-GNR were distributed into all skin
      compartments, especially the dermis (~11.5% of the total applied dose), which
      exhibits hydrophilic characteristics. Charged GNR showed a negligible percentage
      of penetration into any of the skin compartments. GNR could be a promising
      approach for targeted skin disease treatment and transdermal administration of
      drugs and therapy.

PMID- 28502718
TI  - Mitochondrial ND5 mutation mediated elevated ROS regulates apoptotic pathway
      epigenetically in a P53 dependent manner for generating pro-cancerous phenotypes.
AB  - We have previously observed concomitant events of mutations in mitochondrial and
      nuclear genes, along with elevated reactive oxygen species (ROS) and differential
      methylation within the promoters of nuclear genes in tumors and in vitro
      experiments of tumorigenesis. These observations have made it pertinent to
      replicate and understand the role of acquired mitochondrial condition in tuning a
      cell to accomplish a pro-cancerous state. Using a codon optimized vector system
      for exogenous over-expression and mitochondrial localization; we have
      characterized here the role of over-expressed wild type mtND5 and one of its non
      synonymous somatic mutation, ND5:P265H. The ectopically over-expressed ND5:P265H
      in mitochondria resulted in a reduced Complex I activity, generation of higher
      ADP/ATP ratio, reactive oxygen species (ROS) and carbonylation of proteins as
      compared to mock-transfected cells. Cells over-expressing mtND5 variant produced
      both peroxide as well as super-oxide ROS; the generation of which was dependent
      on the functional status of P53; modulating epigenetically the expression of key
      apoptosis pathway genes. The pro-cancerous phenotypes, of anchorage dependent and
      independent growth; increased glucose uptake and lactate production, were
      selectively observed only in P53 non-functional cells over-expressing mutant
      ND5:P265H. We propose that somatic mutation in mtND5 resulting in down-regulated
      complex I enzyme activity, elevated ROS and up-regulation of a set of nuclear
      anti-apoptotic genes epigenetically in the P53 dysfunctional cellular background,
      has provided a unique understanding of the molecular mechanism of mitochondrial
      mutation; and the concomitant existence of somatically acquired mitochondrial and
      nuclear p53 mutations, in cancer progression and promotion.

PMID- 28502719
TI  - Re: Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for
      Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial
      Carcinoma.

PMID- 28502720
TI  - Insights into the chicken IgY with emphasis on the generation and applications of
      chicken recombinant monoclonal antibodies.
AB  - The advantages of chicken (Gallus gallus domesticus) antibodies as
      immunodiagnostic and immunotherapeutic biomolecules has only been recently
      recognized. Even so, chicken antibodies remain less-well characterized than their
      mammalian counterparts. This review aims at providing a current overview of the
      structure, function, development and generation of chicken antibodies.
      Additionally, brief but comprehensive insights into current knowledge pertaining
      to the immunogenetic framework and diversity-generation of the chicken
      immunoglobulin repertoire which have contributed to the establishment of
      recombinant chicken mAb-generating methods are discussed. Focus is provided on
      the current methods used to generate antibodies from chickens with added emphasis
      on the generation of recombinant chicken mAbs and its derivative formats. The
      advantages and limitations of established protocols for the generation of chicken
      mAbs are highlighted. The various applications of recombinant chicken mAbs and
      its derivative formats in immunodiagnostics and immunotherapy are further
      detailed.

PMID- 28502722
TI  - Radiotherapy Rescue of a Nivolumab-Refractory Immune Response in a Patient with
      PD-L1-Negative Metastatic Squamous Cell Carcinoma of the Lung.

PMID- 28502721
TI  - MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic
      Implications and Prognostic Values.
AB  - INTRODUCTION: Response to mesenchymal-epithelial transition (MET) inhibitors in
      NSCLC with mesenchymal-epithelial transition gene (MET) exon 14 skipping
      (METex14) has fueled molecular screening efforts and the search for optimal
      therapies. However, further work is needed to refine the clinicopathologic and
      prognostic implications of METex14 skipping. METHODS: Among 795 East Asian
      patients who underwent a surgical procedure for NSCLC, we screened 45 patients
      with quintuple-negative (EGFR-negative/KRAS-negative/anaplastic lymphoma kinase
      gene [ALK]-negative/ROS1-negative/ret proto-oncogene [RET]-negative) lung
      adenocarcinomas by using reverse-transcriptase polymerase chain reaction and
      found 17 patients (37.8%) with METex14 skipping. We also investigated the effect
      of small interfering RNA (siRNA) targeting skipping junction in cells with
      METex14 skipping. RESULTS: The median age of the 17 patients was 73 years. The
      acinar subtype was predominant (52.9%), followed by the solid subtype (35.3%).
      MET immunohistochemistry demonstrated 100% sensitivity and 70.4% specificity.
      Multivariate analyses showed that patients with METex14 skipping had a higher
      recurrence rate than those with ALK fusion (versus METex14 skipping) (hazard
      ratio = 0.283, 95% confidence interval: 0.119-0.670) in stage I to IIIA disease;
      however, the differences in overall survival were not significant after
      adjustment for pathologic stage (p = 0.669). Meanwhile, siRNA decreased MET
      driven signaling pathways in Hs746T cells, and combined treatment with siRNA and
      crizotinib inhibited cell proliferation in crizotinib-resistant H596 cells.
      CONCLUSIONS: The prevalence of METex14 skipping was quite high in East Asian
      patients without other driver mutations in lung adenocarcinomas. METex14 skipping
      was associated with old age, the acinar or solid histologic subtype, and high MET
      immunohistochemical expression. The prognosis of patients with METex14 skipping
      was similar to that of patients with major driver mutations. siRNA targeting the
      junction of METex14 skipping could inhibit MET-driven signaling pathways in cells
      with METex14 skipping.

PMID- 28502723
TI  - Histologic Transformation in NSCLC with PD-1 therapy.

PMID- 28502724
TI  - Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions.

PMID- 28502725
TI  - Molecular Diagnosis of Mosaic Overgrowth Syndromes Using a Custom-Designed Next
      Generation Sequencing Panel.
AB  - Recent studies have discovered a group of overgrowth syndromes, such as
      congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies
      (CLOVES) syndrome, Proteus syndrome, and megalencephaly-capillary malformation
      polymicrogyria (MCAP) syndrome, are caused by somatic activating variants in
      genes involved in the phosphatidylinositol 3-kinase/AKT/mechanistic target of
      rapamycin pathway. Because of the low-abundance nature of these variants, Sanger
      sequencing often yields negative results. We have developed and validated a next
      generation sequencing (NGS) panel that targets all known variants associated with
      these syndromes. Fifty cases, including two prenatal cases, were tested using the
      panel. A pathogenic variant in the PIK3CA, PIK3R2, or AKT1 gene was identified in
      28 of the 50 cases with the variant allele frequencies ranging from 1.0% to
      49.2%. These variants were only present in the affected tissues in most of the
      cases, demonstrating a causal role in the development of these diseases. In vitro
      cell culture showed significant enrichment of the cells harboring variant
      alleles, suggesting that these variants render growth advantages to mutant cells.
      Phenotype-genotype correlation analysis showed PIK3CA mutation hotspots at
      residues E542, E545, and H1047 are often associated with CLOVES syndrome, whereas
      PIK3CA G914R is preferentially related to MCAP. We thus demonstrate that NGS
      technology is highly sensitive for detecting low-level mosaicism and can
      facilitate clinical diagnosis of mosaic overgrowth syndromes in both prenatal and
      postnatal settings.

PMID- 28502726
TI  - Utility of NIST Whole-Genome Reference Materials for the Technical Validation of
      a Multigene Next-Generation Sequencing Test.
AB  - The sensitivity and specificity of next-generation sequencing laboratory
      developed tests (LDTs) are typically determined by an analyte-specific approach.
      Analyte-specific validations use disease-specific controls to assess an LDT's
      ability to detect known pathogenic variants. Alternatively, a methods-based
      approach can be used for LDT technical validations. Methods-focused validations
      do not use disease-specific controls but use benchmark reference DNA that
      contains known variants (benign, variants of unknown significance, and
      pathogenic) to assess variant calling accuracy of a next-generation sequencing
      workflow. Recently, four whole-genome reference materials (RMs) from the National
      Institute of Standards and Technology (NIST) were released to standardize methods
      based validations of next-generation sequencing panels across laboratories. We
      provide a practical method for using NIST RMs to validate multigene panels. We
      analyzed the utility of RMs in validating a novel newborn screening test that
      targets 70 genes, called NEO1. Despite the NIST RM variant truth set originating
      from multiple sequencing platforms, replicates, and library types, we discovered
      a 5.2% false-negative variant detection rate in the RM truth set genes that were
      assessed in our validation. We developed a strategy using complementary non-RM
      controls to demonstrate 99.6% sensitivity of the NEO1 test in detecting variants.
      Our findings have implications for laboratories or proficiency testing
      organizations using whole-genome NIST RMs for testing.

PMID- 28502728
TI  - Technical Validation of a Next-Generation Sequencing Assay for Detecting
      Clinically Relevant Levels of Breast Cancer-Related Single-Nucleotide Variants
      and Copy Number Variants Using Simulated Cell-Free DNA.
AB  - Next-generation sequencing (NGS) is commonly used in a clinical setting for
      diagnostic and prognostic testing of genetic mutations to select optimal targeted
      therapies. Herein, we describe the development of a custom NGS assay for
      detecting single-nucleotide variants (SNVs) and copy number variations (CNVs) in
      a panel of 51 genes related to breast cancer. We designed and implemented a
      validation strategy in accordance with principles and guidelines developed by the
      Next-Generation Sequencing: Standardization of Clinical Testing work group using
      artificial, cell-free DNA (cfDNA) with mutant fragments prepared in a simple,
      rapid, and cost-effective manner. For SNV detection, our test had 96.30%
      sensitivity at mutant allele frequency >=0.5% with high specificity (99.9997%)
      and accuracy (99.9996%). For CNV detection, the approach had 95.83% sensitivity
      for copy numbers at 1.25* (25.6% extra copies) with high specificity (99.77%) and
      accuracy (99.76%). In addition, our NGS-based assay demonstrated high intrarun
      and interrun reproducibility, high consistency compared to digital PCR, and a low
      cross-contamination rate. An overall assessment using cfDNA and plasma cfDNA
      samples demonstrated our custom NGS assay yields a reliable and robust detection
      sensitivity with a mutant allele frequency as low as 0.5% for SNVs and copy
      number of 1.25* for CNVs.

PMID- 28502729
TI  - Improving Mutation Screening in Patients with Colorectal Cancer Predisposition
      Using Next-Generation Sequencing.
AB  - Identification of genetic alterations is important for family risk assessment in
      colorectal cancers. Next-generation sequencing (NGS) technologies provide useful
      tools for single-nucleotide and copy number variation (CNV) identification in
      many genes and samples simultaneously. Herein, we present the validation of
      current Multiplicom MASTR designs of mismatch repair combined to familial
      adenomatous polyposis genes in a single PCR reamplification test for eight DNA
      samples simultaneously on a MiSeq apparatus. Blood samples obtained from 224
      patients were analyzed. We correctly identified the 97 mutations selected among
      48 samples tested in a validation cohort. PMS2 NGS analysis of the eight positive
      controls identified single-nucleotide variations not detected with targeted
      referent methods. As NGS method could not discriminate if some of them were
      assigned to PMS2 or pseudogenes, only CNV analysis with multiplex ligand probe
      dependent amplification confirmation was retained for clinical use. Twenty-seven
      new variants of unknown significance, 21 disease-causing variants, and two CNVs
      were detected among the 176 patient samples analyzed in diagnosis routine. MUTYH
      disease-causing mutations were identified in two patient samples assessed for
      mismatch repair testing, confirming that this method facilitates accurate and
      rapid individual risk assessments. In one sample, the MUTYH mutation was
      associated with a MSH6 disease-causing mutation, suggesting that this method is
      helpful to identify additional cancer risk modifiers and provides a useful tool
      to optimize clinical issues.

PMID- 28502727
TI  - Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping
      in the eMERGE-PGx Study.
AB  - There has been extensive debate about both the necessity of orthogonal
      confirmation of next-generation sequencing (NGS) results in Clinical Laboratory
      Improvement Amendments-approved laboratories and return of research NGS results
      to participants enrolled in research studies. In eMERGE-PGx, subjects underwent
      research NGS using PGRNseq and orthogonal targeted genotyping in clinical
      laboratories, which prompted a comparison of genotyping results between
      platforms. Concordance (percentage agreement) was reported for 4077 samples
      tested across nine combinations of research and clinical laboratories. Retesting
      was possible on a subset of 1792 samples, and local laboratory directors
      determined sources of genotype discrepancy. Research NGS and orthogonal clinical
      genotyping had an overall per sample concordance rate of 0.972 and per variant
      concordance rate of 0.997. Genotype discrepancies attributed to research NGS were
      because of sample switching (preanalytical errors), whereas the majority of
      genotype discrepancies (92.3%) attributed to clinical genotyping were because of
      allele dropout as a result of rare variants interfering with primer hybridization
      (analytical errors). These results highlight the analytical quality of clinically
      significant pharmacogenetic variants derived from NGS and reveal important areas
      for research and clinical laboratories to address with quality management
      programs.

PMID- 28502730
TI  - Overgrowth Syndromes Caused by Somatic Variants in the Phosphatidylinositol 3
      Kinase/AKT/Mammalian Target of Rapamycin Pathway.
AB  - Somatic variants have been well described in tumorigenesis; however, they are
      only recently appreciated in other human disorders, such as mosaic overgrowth
      syndromes. Although overgrowth is a manifestation in many genetic syndromes, not
      all overgrowth syndromes are inherited. Mosaic somatic variants have been lately
      described in several overgrowth disorders, such as Proteus syndrome, CLOVES
      (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and
      spinal/skeletal anomalies and/or scoliosis) syndrome, and
      megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. These syndromes
      are caused by somatic variants in the genes associated with the
      phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway,
      resulting in a spectrum of overgrowth syndromes with overlapping features that
      could be difficult to distinguish based on phenotypic presentations alone. In
      addition, Sanger sequencing is ineffective for the detection of a causal variant
      because of the mosaic nature of these variants, whereas targeted next-generation
      sequencing technology offers a deeper sequencing coverage and allows the
      detection of low-level mosaicism. Recent studies have shown that the causal
      variants are only present in the affected tissues in most cases, and can be
      enriched by in vitro tissue culture. In this review, we describe several mosaic
      somatic overgrowth syndromes caused by variants in genes of the
      phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling
      pathway, their phenotypic and molecular spectrum, and the clinical utility of
      next-generation sequencing technology in the diagnosis of these disorders.

PMID- 28502731
TI  - The influence of a probiotic supplementation on memory in quail suggests a role
      of gut microbiota on cognitive abilities in birds.
AB  - The gut microbiota is involved in host behaviour and memory in mammals.
      Consequently, it may also influence emotional behaviour and memory in birds.
      Quail from two genetic lines with different fearfulness (LTI: long tonic
      immobility, n=37; STI: short tonic immobility, n=32) were either or not
      supplemented with a probiotic (Pediococcus acidilactici) from hatching. Emotional
      reactivity was measured in a tonic immobility test (d6 and 7 of age) and two open
      field tests (d13-15; d22-24). Memory was measured in a test rewarded with
      mealworms, where quail had to remember the cups previously visited (d34-36).
      Quail endured a 5-days stress period from days 17 to 21 to help revealing the
      potentially beneficial effect of the probiotic. As expected, STI quail were less
      fearful compared to the LTI quail (p<0.05). Probiotic supplementation had no
      effect on most measures of emotional reactivity (p>0.05), except in the tonic
      immobility test where supplemented STI quail had lower immobility duration
      (p=0.0001). Regarding the memory test, the two lines had similar performances.
      Quail fed with probiotics made fewer errors (p=0.040). There was no significant
      correlation between traits of emotional reactivity and of memory. In conclusion,
      the supplementation with Pediococcus acidilactici as a probiotic, affected a
      specific trait of emotional reactivity in STI quail, and improved memory in both
      lines, whichstrengthens the idea that the influence of gut microbiota on the host
      behaviour and memory seen in mammals is shared by birds.

PMID- 28502732
TI  - Swimming exercise prevents behavioural disturbances induced by an
      intracerebroventricular injection of amyloid-beta1-42 peptide through modulation
      of cytokine/NF-kappaB pathway and indoleamine-2,3-dioxygenase in mouse brain.
AB  - Emerging evidence indicates that the activation of indoleamine-2,3-dioxygenase
      (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is
      involved in amyloid-beta (Abeta1-42)-neurotoxicity and Alzheimer's disease (AD)
      pathogenesis. Physical exercise has been considered an effective intervention in
      AD, attenuating or limiting their progression. Nevertheless, the neurobiological
      mechanisms underlying the neuroprotective effects of exercise have not yet been
      fully elucidated. In present study, we investigated the protective effect of an 8
      week swimming training (ST) exercise on cognitive and non-cognitive functions and
      its role in modulating biomarkers of KYN pathway, before an
      intracerebroventricular (i.c.v.) injection of Abeta1-42 (400pmol/animal;
      3MUl/site) peptide in mice. Our results demonstrated that ST was effective in
      preventing the following behavioural disturbances caused by Abeta1-42 injection:
      memory impairment in the object recognition test and depressive/anxiety-like
      behaviour in the tail suspension test and elevated plus-maze test, respectively.
      ST abrogated the neuroinflammatory response and neurotrophic deficiency in the
      prefrontal cortex and hippocampus induced by Abeta1-42. Also, Abeta1-42 increased
      IDO activity, KYN and tryptophan (TRP) levels and KYN:TRP ratio in the prefrontal
      cortex and hippocampus - alterations that were blocked by ST. It can be concluded
      that ST prevented behavioural and neurobiological deficits induced by Abeta1-42,
      and suggest that these neuroprotective effects are likely to involve the
      inhibition of inflammation/IDO activation and up-regulation of neurotrophic
      factors in brain of mice. Thus, it is possible that physical exercise can be used
      as a non-pharmacological approach to alleviates both cognitive and non-cognitive
      symptoms of AD.

PMID- 28502734
TI  - Transcatheter aortic valve implantation in patients at intermediate surgical
      risk.
AB  - Transcatheter Aortic Valve Implantation (TAVI) has revolutionized the treatment
      of elderly patients with symptomatic severe aortic stenosis (AS). Initially
      tested in unoperable or high surgical risk patients, the safety and efficacy of
      TAVI has progressively improved, with increasing operators' experience and
      continuous technical refinements of the devices and of the delivery systems.
      Hence, the extension of clinical indications for TAVI to the intermediate-risk
      population has been attracting cardiologists in recent years. This idea was
      supported by the results of recent studies suggesting that transfemoral TAVI
      might be associated with a survival benefit in both high- and intermediate-risk
      patients with severe AS. Therefore, the aim of this review is to summarize the
      currently available evidence from multiple observational studies, substudies from
      large country registries, mached group comparisons, a substudy of randomized
      studies, and randomized trials, as well as in recent meta-analyses on the use of
      TAVI in patient at intermediate-risk for surgery.

PMID- 28502733
TI  - Reduced anxiety-like behavior in transgenic rats with chronically overproduction
      of angiotensin-(1-7): Role of the Mas receptor.
AB  - Angiotensin-(1-7) [Ang-(1-7)], a counterregulatory peptide of the renin
      angiotensin system (RAS), exerts its cardiovascular and renal functions through
      the G-protein-coupled receptor Mas. More recently, Ang-(1-7) has also been
      implicated in the control of emotional states related to fear and anxiety. Here,
      we tested the hypothesis that transgenic rats overexpressesing Ang-(1-7) (TGR)
      show reduced anxiety-like behavior in two distinct animals models, the Elevated
      Plus Maze (EPM) and Vogel Conflict Test (VCT). Sprague-Dawley rats (SDs) were
      used as controls. In addition, we also verified whether this phenotype depend on
      activation of the Mas receptor. In line with our hypothesis, TGR rats showed an
      increase in the percentage of time and entries in the open arms of the EPM. There
      was also an increase in the number of punished licks in VCT. These phenotypes
      were reversed by ICV injection of the Mas receptor antagonist, A779, but not by
      the AT2 and MrgD receptor antagonist, PD123319. These results suggest that
      chronic elevation of Ang-(1-7) levels results in a phenotype characterized by
      reduced anxiety-like behavior, possibly due to higher activation of the Mas
      receptor. Therefore, facilitation of the Ang-(1-7)/Mas receptor signaling may be
      further investigated as an additional strategy for the treatment of anxiety
      related disorders.

PMID- 28502735
TI  - Effects of low calcium dialysate on the progression of coronary artery
      calcification in hemodialysis patients: An open-label 12-month randomized
      clinical trial.
AB  - BACKGROUND: The association between the dialysate calcium level and coronary
      artery calcification (CAC) has not yet been evaluated in hemodialysis patients.
      The objective of this study was to determine whether lowering the dialysate
      calcium levels would decrease the progression of coronary artery calcification
      (CAC) compared to using standard calcium dialysate. METHODS: We conducted an open
      label randomized trial with parallel groups. The patients were randomly assigned
      to either 12-month treatment with low calcium dialysate (LCD; 1.25mmol/L, n=36)
      or standard calcium dialysate (SCD; 1.5mmol/L, n=40). The primary outcome was the
      change in the CAC scores assessed by 64-slice multidetector computed tomography
      after 12months. RESULTS: During the treatment period, CAC scores increased in
      both groups, especially significant in LCD group (402.5+/-776.8, 580.5+/-1011.9,
      P=0.004). When we defined progressors as patients at second and third tertiles of
      CAC changes, progressor group had a higher proportion of LCD-treated patients
      than SCD-treated patients (P=0.0229). In multivariate analysis, LCD treatment is
      a significant risk factor for increase in CAC scores (odds ratio=5.720, 95% CI:
      1.219-26.843, P=0.027). CONCLUSIONS: Use of LCD may accelerate the progression of
      CAC in patients with chronic hemodialysis over a 12-month period. TRIAL
      REGISTRATION: Clinical Research Information Service [Internet]; Osong
      (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry
      of Health and Welfare (Republic of Korea), 2010: KCT0000942. Available from:
      https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=3572&sLeft=2&t
      pe=my.

PMID- 28502736
TI  - Positive family history of aortic dissection dramatically increases dissection
      risk in family members.
AB  - OBJECTIVES: Although family members of patients with aortic dissection (AoD) are
      believed to be at higher risk of AoD, the prognostic value of family history (FH)
      of aortic dissection (FHAD) in family members of patients with AoD has not been
      studied rigorously. We seek examine how much a positive FHAD increases the risk
      of developing new aortic dissection (AoD) among first-degree relatives. METHODS:
      Patients with AoD at our institution were analyzed for information of FHAD.
      Positive FHAD referred to that AoD occurred in index patient and one or more
      first-degree relatives. Negative FHAD was defined as the condition in which only
      one case of AoD (the index patient) occurred in the family. The age at AoD,
      exposure years in adulthood before AoD, and annual probability of AoD among first
      degree relatives were compared between patients with negative and positive FHADs.
      RESULTS: FHAD was positive in 32 and negative in 68 among the 100 AoD patients
      with detailed family history information. Mean age at dissection was 59.9+/
      14.7years. Compared to negative FHAD, patients with positive FHAD dissected at
      significantly younger age (54.7+/-16.8 vs 62.4+/-13.0years, p=0.013), had more
      AoD events in first-degree relatives (2.3+/-0.6 vs 1.0+/-0.0, p<0.001), and
      shorter exposure years per AoD event (18.3+/-6.7 vs 43.1+/-8.5, p<0.001). Annual
      probability of AoD per first-degree relative was 2.77 times higher in patients
      with positive than negative FHADs (0.0100+/-0.0057 vs 0.0036+/-0.0014, p<0.001).
      CONCLUSIONS: A positive FHAD confers a significantly increased risk of developing
      aortic dissection on family members, with a higher annual probability of aortic
      dissection, a shorter duration of "exposure time" before dissection occurs and a
      lower mean age at time of dissection.

PMID- 28502738
TI  - Maternal emotional feeding practices and adolescent daughters' emotional eating:
      Mediating roles of avoidant and preoccupied coping.
AB  - The current study examined the link between early childhood emotional feeding and
      adolescent girls' emotional eating, using maladaptive coping styles as the
      underlying mechanisms mediating these associations. We examined adolescent girls'
      and mothers' retrospective reports of emotional feeding during childhood, as well
      as adolescent girls' current reports of their coping behaviors (i.e., preoccupied
      and avoidant) and emotional eating. Findings showed that adolescent girls' and
      mothers' retrospective reports of early emotional feeding were positively
      associated with adolescent girls' emotional eating. Preoccupied coping, but not
      avoidant coping, mediated the associations between early emotional feeding
      (reported by adolescents and mothers) and adolescents' current emotional eating.
      In conclusion, findings suggest that early childhood feeding experiences are
      linked to the development of maladaptive coping and emotional eating among
      adolescent girls.

PMID- 28502737
TI  - Gel-free/label-free proteomic, photosynthetic, and biochemical analysis of cowpea
      (Vigna unguiculata [L.] Walp.) resistance against Cowpea severe mosaic virus
      (CPSMV).
AB  - : Cowpea severe mosaic virus (CPSMV) causes significant losses in cowpea (Vigna
      unguiculata) production. In this present study biochemical, physiological, and
      proteomic analysis were done to identify pathways and defense proteins that are
      altered during the incompatible interaction between the cowpea genotype BRS
      Marataoa and CPSMV. The leaf protein extracts from mock- (MI) and CPSMV
      inoculated plantlets (V) were evaluated at 2 and 6days post-inoculation (DPI).
      Data support the assumptions that increases in biochemical (high hydrogen
      peroxide, antioxidant enzymes, and secondary compounds) and physiological
      responses (high photosynthesis index and chlorophyll content), confirmed by label
      free comparative proteomic approach, in which quantitative changes in proteasome
      proteins, proteins related to photosynthesis, redox homeostasis, regulation
      factors/RNA processing proteins were observed may be implicated in the resistance
      of BRS-Marataoa to CPSMV. This pioneering study provides information for the
      selection of specific pathways and proteins, altered in this incompatible
      relationship, which could be chosen as targets for detailed studies to advance
      our understanding of the molecular, physiological, and biochemistry basis of the
      resistance mechanism of cowpea and design approachs to engineer plants that are
      more productive. BIOLOGICAL SIGNIFICANCE: This is a pioneering study in which an
      incompatible relationship between a resistant cowpea and Cowpea severe mosaic
      virus (CPSMV) was conducted to comparatively evaluate proteomic profiles by Gel
      free/label-free methodology and some physiological and biochemical parameters to
      shed light on how a resistant cowpea cultivar deals with the virus attack.
      Specific proteins and associated pathways were altered in the cowpea plants
      challenged with CPSMV and will contribute to our knowledge on the biological
      process tailored by cowpea in response to CPSMV.

PMID- 28502739
TI  - The Hunger Games: Using hunger to promote healthy choices in self-control
      conflicts.
AB  - The majority of existing research and conventional wisdom would advise against
      shopping on an empty stomach as hunger is assumed to encourage impulsive choices
      that typically lead to self-control failure (i.e., favouring short-term
      gratifications at the expense of long-term goals). Nonetheless, through two
      studies the current research aims to demonstrate that hungry consumers would not
      always be disadvantaged when encountering a self-control conflict involving a
      trade-off choice between a healthy vs. a more palatable but unhealthy choice.
      Particularly we posit that the choice outcome of the self-control conflict is
      dependent on contextual cues, such that hungry consumers with the tendency to
      make fast decisions could benefit from following a social proof heuristic
      promoting the healthy options. In Study 1, we indeed observed participants' self
      reported hunger to be negatively associated with state self-control, but as most
      participants generally experienced low levels of hunger we did not observe
      apparent effects of hunger on food choice (DV), and correspondingly the potential
      influence of the social proof heuristic in moderating the choice outcome.
      However, in Study 2 where hunger was manipulated, we found hungry participants
      making significantly less healthy choices than satiated participants, but a
      social proof heuristic mitigated this effect (i.e., in the presence of social
      proof heuristic hungry participants made just as many healthy food choices as
      satiated participants; and hungry participants made more healthy choices in the
      social proof condition than in the no heuristic condition). These findings
      support our approach of providing contextual cues in the environment in order to
      work with, rather than against, the impulsivity triggered by hunger to promote
      successful self-control behaviours.

PMID- 28502740
TI  - Isolation of an insulin-like peptide from the Asian malaria mosquito, Anopheles
      stephensi, that acts as a steroidogenic gonadotropin across diverse mosquito
      taxa.
AB  - Many insulin-like peptides (ILPs) have been identified in insects, yet only a few
      were isolated in their native form for structural and functional studies.
      Antiserum produced to ILP3 in Aedes aegypti was used in a radioimmunoassay to
      monitor the purification of an ILP from heads of adult An. stephensi and
      recognized the ILP in other immunoassays. The structure of the purified peptide
      matched that predicted for the ILP3 in this species. The native form stimulated
      ecdysteroid production by ovaries isolated from non-blood fed females. Synthetic
      forms of An. stephensi ILP3 and ILP4 similarly activated this process in a dose
      responsive manner. This function was first established for ILP3 and ILP4 homologs
      in Aedes aegypti, thus suggesting their structural and functional conservation in
      mosquitoes. We tested the extent of conservation by treating ovaries of An.
      gambiae, Ae. aegypti, and Culex quinquefasciatus with the An. stephensi ILPs, and
      both the native and synthetic ILP3 were stimulatory, as was the ILP4. Taken
      together, these results offer the first evidence for ILP functional conservation
      across the Anophelinae and Culicinae subfamilies.

PMID- 28502741
TI  - High metabolic activity of tissue-nonspecific alkaline phosphatase not only in
      young but also in adult bone as demonstrated using a new histochemical detection
      protocol.
AB  - Tissue-nonspecific alkaline phosphatase (TNAP) is playing a key role in bone
      calcification, as has been demonstrated in different mammalian species including
      human and rodents. However, to investigate age-related changes during life
      history, histochemical demonstration of TNAP is severely hampered, particularly
      in the elderly, by technical difficulties associated with sectioning calcified
      tissue. Sufficient fixation must precede decalcification since poorly fixed bone
      tissue is exposed to the deleterious effects of decalcification reagents. In
      order to find a method that would allow cryosectioning of bone without loss of
      TNAP activity, we assessed the efficacy of different fixation reagents regarding
      the effects on structural integrity and TNAP activity using liver and osseous
      tissue from younger and older horses. The results of this study reveal that
      glyoxal-based fixatives sufficiently preserved bone tissue for successful
      cryosectioning without compromising TNAP activity. The method described combines
      the demonstration of TNAP activity with optimal preservation of tissue morphology
      in osseous tissue of younger and even of older mammals. As a model species, we
      selected horse bones in light of potentially higher similarities to ageing
      history and lifelong locomotion in humans as compared to other, mostly smaller,
      experimental model species with a much shorter life span and artificial
      locomotive activity when kept in cages. This may serve as a basis for future
      studies addressing the impact of different life traits in iconic, domestic and
      companion animals, which are often patients in veterinary medicine, as well as
      for basic research on human physiology and pathologies of the musculoskeletal
      system.

PMID- 28502742
TI  - Seasonal changes of androgen receptor, estrogen receptors and aromatase
      expression in the hippocampus of the wild male ground squirrels (Citellus
      dauricus Brandt).
AB  - The wild ground squirrel is a typical seasonal breeder whose annual life cycle
      can be roughly divided into the breeding season, the post-breeding season and
      hibernation. Our previous study has reported the seasonal changes in the
      expressions of androgen receptor (AR), estrogen receptors alpha and beta (ERalpha
      and ERbeta), and aromatase cytochrome P450 (P450arom) in the hypothalamus of male
      wild ground squirrels. To further seek evidence of seasonal expression of steroid
      hormone receptors and steroid hormone synthases in other brain regions, we
      investigated the protein and mRNA expressions of AR, ERalpha, ERbeta and P450arom
      in the hippocampus of the male wild ground squirrels during these different
      reproductive periods. Histological observation showed that the number of
      pyramidal cells in Cornu Ammonis 1 (CA1) increased in the breeding season. Both
      protein and mRNA of AR, ERalpha, ERbeta and P450arom were present in CA1 and CA3
      of all seasons. There was significant increment in the immune-signal intensity
      and mRNA level of AR and ERalpha during the pre-hibernation, whereas those of
      ERbeta and P450arom were higher during the post-breeding season. In addition, the
      profile of plasma testosterone concentration showed the nadir in the post
      breeding season, a marked elevation in the pre-hibernation, and the summit in the
      breeding season. These findings suggested that the hippocampus may be a direct
      target of androgen and estrogen; androgen may play important regulatory roles
      through its receptor and/or the aromatized estrogen in the hippocampus of the
      wild male ground squirrels.

PMID- 28502743
TI  - Reply to Garcia J. et al.

PMID- 28502744
TI  - Effect of high-dose sodium selenite in cardiac surgery patients: A randomized
      controlled bi-center trial.
AB  - BACKGROUND & AIMS: Cardiac surgery is accompanied by oxidative stress and
      systemic inflammatory response, which may be associated with organ dysfunction
      and increased mortality. Selenium and selenoenzymes are important constituents of
      anti-oxidative defense. We hypothesized that high-dose sodium selenite
      supplementation can attenuate the postoperative inflammation and might,
      therefore, improve clinical outcome. METHODS: Randomized, placebo-controlled,
      double-blinded, bi-center study on 411 adult patients undergoing elective cardiac
      surgery. Patients received an intravenous bolus of 4000 MUg selenium (in the form
      of sodium selenite) or placebo after induction of anesthesia and 1000 MUg/d
      selenium or placebo during their intensive care unit (ICU) stay. Primary outcome
      measure was the Sequential Organ Failure Assessment (SOFA) score on the second
      postoperative day. Secondary endpoints included the change in perioperative
      selenium levels, change of inflammatory and cardiac markers, use of vasoactive
      medication, incidence of acute kidney injury, ICU and hospital length of stay,
      and mortality. RESULTS: The perioperative administration of high-dose sodium
      selenite prevented the postoperative drop of blood and serum selenium levels,
      reduced the number of patients depending on postoperative vasoactive support but
      failed to reduce the postoperative SOFA score and its related organ-specific
      scores compared to placebo. Except for an increase of postoperative procalcitonin
      and bilirubin levels in the sodium selenite group, other inflammatory markers,
      organ function variables and clinical endpoints remained unchanged. CONCLUSIONS:
      The perioperative administration of high-dose sodium selenite in cardiac surgery
      patients prevented the postoperative fall of blood selenium levels and reduced
      the need for postoperative vasoactive support by a yet unknown mechanism. TRIAL
      REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT01141556.

PMID- 28502745
TI  - Pi5 and Pi6, two undescribed peptides from the venom of the scorpion Pandinus
      imperator and their effects on K+-channels.
AB  - This work reports the isolation, chemical and functional characterization of two
      previously unknown peptides purified from the venom of the scorpion Pandinus
      imperator, denominated Pi5 and Pi6. Pi5 is a classical K+-channel blocking
      peptide containing 33 amino acid residues with 4 disulfide bonds. It is the first
      member of a new subfamily, here defined by the systematic number alpha-KTx 24.1.
      Pi6 is a peptide of unknown real function, containing only two disulfide bonds
      and 28 amino acid residues, but showing sequence similarities to the kappa-family
      of K-channel toxins. The systematic number assigned is kappa-KTx2.9. The function
      of both peptides was assayed on Drosophila Shab and Shaker K+-channels, as well
      as four different subtypes of voltage-dependent K+-channels: hKv1.1, hKv1.2,
      hKv1.3 and hKv1.4. The electrophysiological assays showed that Pi5 inhibited
      Shaker B, hKv1.1, hKv1.2 and hKv1.3 channels with Kd = 540 nM, Kd = 92 nM and Kd
      = 77 nM, respectively, other studied channels were not affected. Of the channels
      tested only hKv1.2 and hKv1.3 were inhibited at 100 nM concentration of Pi6, the
      remaining current fractions were 68% and 77%, respectively. Thus, Pi5 and Pi6 are
      high nanomolar affinity non-selective blockers of hKv1.2 and hKv1.3 channels.

PMID- 28502747
TI  - Chicken egg fetal liver DNA and histopathologic effects of structurally diverse
      carcinogens and non-carcinogens.
AB  - Chicken egg fetal livers were evaluated for histopathological changes produced by
      four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1
      (AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related
      non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2),
      benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic
      hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non
      carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of
      DNA adducts using the 32P nucleotide postlabeling (NPL) assay and for DNA breaks
      using the comet assay. CFA was also assessed in enhanced comet assay for
      oxidative DNA damage induction. Eggs were dosed on days 9- 11 of incubation. For
      genotoxicity evaluation, livers were collected 3h after the last dose. Liver
      qualitative histopathology assessment was performed on days 12 and 18 of
      incubation. CFA was negative for DNA adducts but yielded clear evidence of DNA
      breaks due to oxidative stress. PB and MAN produced no DNA adducts or breaks.
      Liver to body weight ratios were not affected in most groups, but were decreased
      in DEN groups, and increased after PB dosing. Livers from control groups, FLU,
      AFB2, BeP, NDELA, CFA, and MAN groups, displayed a typical hepatocellular
      trabecular pattern at both time points. In contrast, the four genotoxic
      carcinogens induced time- and dose- related interference with fetal liver cell
      processes of proliferation, migration and differentiation, leading to
      hepatocellular and cholangiocellular pleomorphic dysplasia and re-(de-)
      differentiation with distortion of the trabecular pattern. In addition, dosing
      with the high dose of DEN produced gallbladder agenesis. PB induced
      hepatocellular hypertrophy, interference with migration, expressed as distortion
      of the trabecular pattern, and a moderate cholangiocellular dysplasia. In
      summary, histopathological analysis of chicken fetal livers revealed
      developmental anomalies, as well as genotoxicity-induced and, in the case of PB,
      adaptive morphological changes. Thus, the model provides histopathological
      outcomes of molecular effects.

PMID- 28502748
TI  - Cytochrome P450 diversity in the tree of life.
AB  - Sequencing in all areas of the tree of life has produced >300,000 cytochrome P450
      (CYP) sequences that have been mined and collected. Nomenclature has been
      assigned to >41,000 CYP sequences and the majority of the remainder has been
      sorted by BLAST searches into clans, families and subfamilies in preparation for
      naming. The P450 sequence space is being systematically explored and filled in.
      Well-studied groups like vertebrates are covered in greater depth while new
      insights are being added into uncharted territories like horseshoe crab (Limulus
      polyphemus), tardigrades (Hypsibius dujardini), velvet worm
      (Euperipatoides_rowelli), and basal land plants like hornworts, liverworts and
      mosses. CYPs from the fungi, one of the most diverse groups, are being explored
      and organized as nearly 800 fungal species are now sequenced. The CYP clan
      structure in fungi is emerging with 805 CYP families sorting into 32 CYP clans.
      >3000 bacterial sequences are named, mostly from terrestrial or freshwater
      sources. Of 18,379 bacterial sequences downloaded from the CYPED database, all
      are >43% identical to named CYPs. Therefore, they fit in the 602 named P450
      prokaryotic families. Diversity in this group is becoming saturated, however 25%
      of 3305 seawater bacterial P450s did not match known P450 families, indicating
      marine bacterial CYPs are not as well sampled as land/freshwater based bacterial
      CYPs. Future sequencing plans of the Genome 10K project, i5k and GIGA (Global
      Invertebrate Genomics Alliance) are expected to produce more than one million
      cytochrome P450 sequences by 2020. This article is part of a Special Issue
      entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika
      Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.

PMID- 28502750
TI  - Cervical length cut-off in twin pregnancy and preterm labor risk assessment
      algorithm: call for action.

PMID- 28502746
TI  - Diminishing fear: Optogenetic approach toward understanding neural circuits of
      fear control.
AB  - Understanding complex behavioral processes, both learned and innate, requires
      detailed characterization of the principles governing signal flow in
      corresponding neural circuits. Previous studies were hampered by the lack of
      appropriate tools needed to address the complexities of behavior-driving micro-
      and macrocircuits. The development and implementation of optogenetic
      methodologies revolutionized the field of behavioral neuroscience, allowing
      precise spatiotemporal control of specific, genetically defined neuronal
      populations and their functional connectivity both in vivo and ex vivo, thus
      providing unprecedented insights into the cellular and network-level mechanisms
      contributing to behavior. Here, we review recent pioneering advances in
      behavioral studies with optogenetic tools, focusing on mechanisms of fear-related
      behavioral processes with an emphasis on approaches which could be used to
      suppress fear when it is pathologically expressed. We also discuss limitations of
      these methodologies as well as review new technological developments which could
      be used in future mechanistic studies of fear behavior.

PMID- 28502749
TI  - A relevant IgE-reactive 28kDa protein identified from Salsola kali pollen extract
      by proteomics is a natural degradation product of an integral 47kDa
      polygalaturonase.
AB  - A highly prevalent IgE-binding protein band of 28kDa is observed when Salsola
      kali pollen extract is incubated with individual sera from Amaranthaceae pollen
      sensitized patients. By an immunoproteomic analysis of S. kali pollen extract, we
      identified this protein band as an allergenic polygalacturonase enzyme. The
      allergen, named Sal k 6, exhibits a pI of 7.14 and a molecular mass of
      39,554.2Da. It presents similarities to Platanaceae, Poaceae, and Cupressaceae
      allergenic polygalacturonases. cDNA-encoding sequence was subcloned into the
      pET41b vector and produced in bacteria as a His-tag fusion recombinant protein.
      The far-UV CD spectrum determined that rSal k 6 was folded. Immunostaining of the
      S. kali pollen protein extract with a rSal k 6-specific pAb and LC-MS/MS
      proteomic analyses confirmed the co-existence of the 28kDa band together with an
      allergenic band of about 47kDa in the pollen extract. Therefore, the 28kDa was
      assigned as a natural degradation product of the 47kDa integral
      polygalacturonase. The IgE-binding inhibition to S. kali pollen extract using
      rSal k 6 as inhibitor showed that signals directed to both protein bands of 28
      and 47kDa were completely abrogated. The average prevalence of rSal k 6 among the
      three populations analyzed was 30%, with values correlating well with the levels
      of grains/m3 of Amaranthaceae pollen. Sal k 6 shares IgE epitopes with Oleaceae
      members (Fraxinus excelsior, Olea europaea and Syringa vulgaris), with IgE
      inhibition values ranging from 20% to 60%, respectively. No IgE-inhibition was
      observed with plant-derived food extracts.

PMID- 28502751
TI  - Comment on: Predicting the difficulty of operative vaginal delivery by ultrasound
      measurement of fetal head station.

PMID- 28502752
TI  - Reply.

PMID- 28502753
TI  - Reply.

PMID- 28502754
TI  - Lifetime cancer risk with progestin and estrogen oral contraceptives and hormone
      therapy.

PMID- 28502755
TI  - Comment on: A randomized clinical trial of exercise during pregnancy to prevent
      gestational diabetes mellitus and improve pregnancy outcome in overweight and
      obese pregnant women.

PMID- 28502756
TI  - Reply.

PMID- 28502757
TI  - The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal
      growth in humans.
AB  - BACKGROUND: The developmentally important DLK1-DIO3 imprinted domain on human
      chromosome 14 is regulated by 2 differentially methylated regions, the intergenic
      differentially methylated region and the MEG3 differentially methylated region.
      OBJECTIVE: The aim was to determine the natural variation in DNA methylation at
      these differentially methylated regions in human placentas, and to determine its
      link to gene expression levels at the domain. The second goal was to explore
      whether the domain's methylation and gene expression correlate with prenatal and
      early postnatal growth of the conceptus. STUDY DESIGN: Using pyrosequencing, we
      determined methylation levels at CpG dinucleotides across the 2 regulatory
      differentially methylated regions in placentas from 91 healthy mothers. At birth,
      placentas and infants were weighed (gestational age 39 +/- 1 weeks; birthweight
      SD score 0.1 +/- 0.8) and placental biopsies were collected. RNA expression was
      quantitated by real-time polymerase chain reaction. Infants' weights and lengths
      were followed up monthly during the first year. RESULTS: Methylation levels at
      the 2 regulatory differentially methylated regions were linked and varied
      considerably between placentas. MEG3 promoter differentially methylated region
      methylation correlated negatively with weight increase (beta = -0.406, P = .001,
      R2 = 0.206) and length increase (beta = -0.363, P = .002, R2 = 0.230) during the
      first postnatal year. The methylation level of the intergenic differentially
      methylated region correlated with DIO3 expression (beta = 0.313, P = .032, R2 =
      0.152). Furthermore, the expression of both DIO3 and RTL1 (both imprinted genes
      within the DLK1-DIO3 domain) was negatively associated with birthweight (beta = 
      0.331, P = .002, R2 = 0.165; and beta = -0.307, P = .005, R2 = 0.159,
      respectively). RTL1 expression, in addition, was negatively linked to birth
      length (beta = -0.306, P = .007, R2 = 0.162). CONCLUSION: Our combined findings
      strongly suggest that placental DNA methylation at the DLK1-DIO3 domain's
      intergenic differentially methylated region and MEG3 promoter differentially
      methylated region relates to measures of early human growth, and may thus
      contribute to its control.

PMID- 28502759
TI  - Reply.

PMID- 28502758
TI  - The impact of postpartum hemorrhage on hospital length of stay and inpatient
      mortality: a National Inpatient Sample-based analysis.
AB  - BACKGROUND: Postpartum hemorrhage is a major cause of maternal morbidity and
      mortality, but the association between postpartum hemorrhage and hospital length
      of stay has not been rigorously investigated. OBJECTIVE: We explored the impact
      of postpartum hemorrhage on hospital length of stay and inpatient mortality, as
      these outcomes have both clinical and economic significance. STUDY DESIGN: We
      performed a retrospective analysis using data from the National Inpatient Sample
      database during the 2012 through 2013 time period. Deliveries were classified as
      postpartum hemorrhage due to uterine atony, nonatonic postpartum hemorrhage, or
      not complicated by postpartum hemorrhage (nonpostpartum hemorrhage). Average
      length of stay and inpatient mortality rates were compared between groups.
      RESULTS: Over the study interval, postpartum hemorrhage occurred in 3% of
      deliveries. Among deliveries complicated by postpartum hemorrhage, 76.6% were
      attributed to uterine atony and 23.4% were nonatonic. Women with nonatonic
      postpartum hemorrhage had the highest average length of stay (3.67 days) followed
      by atonic postpartum hemorrhage (2.98 days) and nonpostpartum hemorrhage (2.63
      days); P < .001, all comparisons. Inpatient mortality rate of nonatonic
      postpartum hemorrhage over the entire study period was 104 per 100,000 compared
      to 019 per 100,000 for atonic postpartum hemorrhage and 3 per 100,000 for
      nonpostpartum hemorrhage deliveries (P < .001). CONCLUSION: From 2012 through
      2013, women with postpartum hemorrhage experienced significantly longer length of
      stay and higher inpatient mortality rates than women without postpartum
      hemorrhage, largely attributable to nonatonic causes of postpartum hemorrhage. As
      hospital length of stay and inpatient mortality are important outcomes from both
      clinical and societal perspectives, interventions to reduce morbidity and
      mortality related to postpartum hemorrhage may simultaneously facilitate delivery
      of more cost-effective care and improve both maternal and population health.

PMID- 28502761
TI  - Delayed admission to ICU in acute respiratory failure: Critical time for critical
      conditions.

PMID- 28502760
TI  - Patterns of gestational weight gain and birthweight outcomes in the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development Fetal
      Growth Studies-Singletons: a prospective study.
AB  - BACKGROUND: Inadequate or excessive total gestational weight gain is associated
      with increased risks of small- and large-for-gestational-age births,
      respectively, but evidence is sparse regarding overall and trimester-specific
      patterns of gestational weight gain in relation to these risks. Characterizing
      the interrelationship between patterns of gestational weight gain across
      trimesters can reveal whether the trajectory of gestational weight gain in the
      first trimester sets the path for gestational weight gain in subsequent
      trimesters, thereby serving as an early marker for at-risk pregnancies.
      OBJECTIVE: We sought to describe overall trajectories of gestational weight gain
      across gestation and assess the risk of adverse birthweight outcomes associated
      with the overall trajectory and whether the timing of gestational weight gain
      (first vs second/third trimester) is differentially associated with adverse
      outcomes. STUDY DESIGN: We conducted a secondary analysis of a prospective cohort
      of 2802 singleton pregnancies from 12 US prenatal centers (2009 through 2013).
      Small and large for gestational age were calculated using sex-specific
      birthweight references <5th, <10th, or >=90th percentiles, respectively. At each
      of the research visits, women's weight was measured following a standardized
      anthropometric protocol. Maternal weight at antenatal clinical visits was also
      abstracted from the prenatal records. Semiparametric, group-based, latent class,
      trajectory models estimated overall gestational weight gain and separate first-
      and second-/third-trimester trajectories to assess tracking. Robust Poisson
      regression was used to estimate the relative risk of small- and large-for
      gestational-age outcomes by the probability of trajectory membership. We tested
      whether relationships were modified by prepregnancy body mass index. RESULTS:
      There were 2779 women with a mean of 15 (SD 5) weights measured across gestation.
      Four distinct gestational weight gain trajectories were identified based on the
      lowest Bayesian information criterion value, classifying 10.0%, 41.8%, 39.2%, and
      9.0% of the population from lowest to highest weight gain trajectories, with an
      inflection at 14 weeks. The average rate in each trajectory group from lowest to
      highest for 0-<14 weeks was -0.20, 0.04, 0.21, and 0.52 kg/wk and for 14-39 weeks
      was 0.29, 0.48, 0.63, and 0.79 kg/wk, respectively; the second lowest gaining
      trajectory resembled the Institute of Medicine recommendations and was designated
      as the reference with the other trajectories classified as low, moderate-high, or
      high. Accuracy of assignment was assessed and found to be high (median posterior
      probability 0.99, interquartile range 0.99-1.00). Compared with the referent
      trajectory, a low overall trajectory, but not other trajectories, was associated
      with a 1.55-fold (95% confidence interval, 1.06-2.25) and 1.58-fold (95%
      confidence interval, 0.88-2.82) increased risk of small-for-gestational-age <10th
      and <5th, respectively, while a moderate-high and high trajectory were associated
      with a 1.78-fold (95% confidence interval, 1.31-2.41) and 2.45-fold (95%
      confidence interval, 1.66-3.61) increased risk of large for gestational age,
      respectively. In a separate analysis investigating whether early (<14 weeks)
      gestational weight gain tracked with later (>=14 weeks) gestational weight gain,
      only 49% (n = 127) of women in the low first-trimester trajectory group continued
      as low in the second/third trimester, and had a 1.59-fold increased risk of small
      for gestational age; for the other 51% (n = 129) of women without a subsequently
      low second-/third-trimester gestational weight gain trajectory, there was no
      increased risk of small for gestational age (relative risk, 0.75; 95% confidence
      interval, 0.47-1.38). Prepregnancy body mass index did not modify the association
      between gestational weight gain trajectory and small for gestational age (P =
      0.52) or large for gestational age (P = .69). CONCLUSION: Our findings are
      reassuring for women who experience weight loss or excessive weight gain in the
      first trimester; however, the risk of small or large for gestational age is
      significantly increased if women gain weight below or above the reference
      trajectory in the second/third trimester.

PMID- 28502762
TI  - Clear cell odontogenic carcinoma, diagnostic difficulties. A case report.
AB  - INTRODUCTION: Clear cell odontogenic carcinoma (COCC) is a rare tumor described
      by Hansen et al. in 1985. The clinical and radiological manifestations are
      multiple and the diagnosis is histological. OBSERVATION: A 64-year-old patient
      consulted us for a right mandibular osteolytic lesion associated to a homolateral
      labial hypoesthesia. A biopsy was performed under local anesthesia. Histology was
      consistent with a metastatic lesion of clear kidney cell carcinoma, COCC, or
      odontogenic squamous tumor. Additional tests eliminated a metastatic lesion. A
      wide excision of the lesion by hemi-mandibulectomy associated with lymph node
      dissection and reconstruction by a fibula osteoseptocutaneous flap was performed.
      Presence of a fission of the EWSR1 gene on the histological examination of the
      surgical specimen made the diagnosis of COCC. DISCUSSION: Our observation
      illustrates the difficulty of diagnosing COCC. The new contribution of the
      cytogenetic techniques such as FISH-type techniques makes possible the
      improvement of the diagnosis.

PMID- 28502763
TI  - Osteomyelitis of the jaws: A retrospective series of 40 patients.
AB  - INTRODUCTION: The caseload of jaw osteomyelitis seem to have decreased
      considerably over the last fifty years thanks to the progress of oral hygiene,
      the appearance and the use of antibiotics, and early screening. 'Limited
      osteitis' remains frequent in general practice (alveolitis after dental
      extraction), but osteomyelitis is much rarer as evidenced by the lack of current
      literature and the low number of reported patients in the published series. The
      aim of this study was to analyze retrospectively all the cases of maxillo
      mandibular osteomyelitis treated in a large academic department of Stomatology
      and Maxillofacial Surgery over a period of 6 years and to compare the results to
      data from the literature. MATERIAL AND METHOD: All patients diagnosed with
      maxillo-mandibular osteomyelitis by one of the staff surgeons between January
      2009 and December 2015 was included. An epidemiological record (sex, age, ethnic
      background, risk factors, clinical, origin of disease, imaging and biology,
      treatments and progression) were collected for each patient. Osteomyelitis cases
      were classified according to the Zurich Classification System. Results were
      compared to data from the literature. RESULTS: Forty patients were retained.
      Three presented acute osteomyelitis, 26 secondary chronic osteomyelitis and 11 a
      primary chronic osteomyelitis. Osteomyelitis affected predominantly the mandible
      (87%). Dental origin was found in 90% of cases. Nine patients (22.5%) recovered
      and 29 (90%) were clinically improved. Ten of the 11 patients with primary
      chronic osteomyelitis were improved. DISCUSSION: This cohort study is one of the
      largest series currently available and presents results comparable to those of
      the literature of the last 25 years.

PMID- 28502764
TI  - Cryptic speciation and gene flow in a migratory songbird Species Complex:
      Insights from the Red-Eyed Vireo (Vireo olivaceus).
AB  - Migratory species that alternate between sympatry and allopatry over the course
      of an annual cycle are promising subjects for studies seeking to understand the
      process of speciation in the absence of strict geographic isolation. Here we
      sought to identify cryptic species and assess rates of gene flow in a clade of
      neotropical migrant songbirds in which geography and taxonomy are currently out
      of sync: the Red-Eyed Vireo (V. olivaceus) Species Complex. Phylogenetic,
      clustering, and statistical species delimitation analyses found that V.
      olivaceusincludes two non-sister lineages migrating in opposite directions across
      the equator. Analyses of gene flow identified low levels of introgression between
      two species pairs, but none between northern and southern olivaceus. We also
      identified substantial well-supported conflicts between nuclear and mitochondrial
      topologies. Although the geographic distribution of mito-nuclear discordance is
      suggestive of hybridization and mitochondrial capture, we found no evidence of
      introgression in the nuclear genome of populations with discordant mitochondrial
      gene trees. Our study finds that species boundaries match breeding range and
      migratory phenology rather than the existing taxonomy in this group, and
      demonstrates the utility of genomic data in inferring species boundaries in
      recently diverged clades.

PMID- 28502765
TI  - Biogeographic links between southern Atlantic Forest and western South America:
      Rediscovery, re-description, and phylogenetic relationships of two rare montane
      anole lizards from Brazil.
AB  - Data on species ranges and phylogenetic relationships are key in historical
      biogeographical inference. In South America, our understanding of the
      evolutionary processes that underlie biodiversity patterns varies greatly across
      regions. Little is known, for instance, about the drivers of high endemism in the
      southern montane region of the Atlantic Rainforest. In this region, former
      biogeographic connections with other South American ecosystems have been invoked
      to explain the phylogenetic affinities of a number of endemic taxa. This may also
      be the case of the montane anole lizards Anolis nasofrontalis and A.
      pseudotigrinus, known from few specimens collected more than 40years ago. We
      combine new genetic data with published sequences of species in the Dactyloa
      clade of Anolis to investigate the phylogenetic relationships of A. nasofrontalis
      and A. pseudotigrinus, as well as estimate divergence times from their closest
      relatives. Based on newly sampled and previously overlooked specimens, we provide
      a taxonomic re-description of those two taxa. Our phylogenetic analysis recovered
      six main clades within Dactyloa, five of which were previously referred to as
      species series (aequatorialis, heterodermus, latifrons, punctatus, roquet). A
      sixth clade clustered A. nasofrontalis and A. pseudotigrinus with A. dissimilis
      from western Amazonia, A. calimae from the Andes, A. neblininus from the Guiana
      Shield, and two undescribed Andean taxa. We therefore define a sixth species
      series within Dactyloa: the neblininus series. Close phylogenetic relationships
      between highly disjunct, narrowly-distributed anoles suggest that patches of
      suitable habitat connected the southern Atlantic Forest to western South America
      during the Miocene, in agreement with the age of former connections between the
      central Andes and the Brazilian Shield as a result of Andean orogeny. The data
      also support the view of recurrent evolution (or loss) of a twig anole-like
      phenotype in mainland anoles, in apparent association with the occurrence in
      montane settings. Our findings stress the value of complementary genetic sampling
      efforts across South American countries to advance studies of mainland anole
      taxonomy and evolution.

PMID- 28502766
TI  - Anterior cingulate serotonin 1B receptor binding is associated with emotional
      response inhibition.
AB  - Serotonin has a well-established role in emotional processing and is a key
      neurotransmitter in impulsive aggression, presumably by facilitating response
      inhibition and regulating subcortical reactivity to aversive stimuli. In this
      study 44 men, of whom 19 were violent offenders and 25 were non-offender
      controls, completed an emotional Go/NoGo task requiring inhibition of prepotent
      motor responses to emotional facial expressions. We also measured cerebral
      serotonin 1B receptor (5-HT1BR) binding with [11C]AZ10419369 positron emission
      tomography within regions of the frontal cortex. We hypothesized that 5-HT1BR
      would be positively associated with false alarms (failures to inhibit nogo
      responses) in the context of aversive (angry and fearful) facial expressions.
      Across groups, we found that frontal cortex 5-HT1BR binding was positively
      correlated with false alarms when angry faces were go stimuli and neutral faces
      were nogo stimuli (p = 0.05, corrected alpha = 0.0125), but not with false alarms
      for non-emotional stimuli (failures to inhibit geometric figures). A posthoc
      analysis revealed the strongest association in anterior cingulate cortex (p =
      0.006). In summary, 5-HT1BRs in the anterior cingulate are involved in
      withholding a prepotent response in the context of angry faces. Our findings
      suggest that serotonin modulates response inhibition in the context of certain
      emotional stimuli.

PMID- 28502767
TI  - Modulating angiogenesis with integrin-targeted nanomedicines.
AB  - Targeting angiogenesis-related pathologies, which include tumorigenesis and
      metastatic processes, has become an attractive strategy for the development of
      efficient guided nanomedicines. In this respect, integrins are cell-adhesion
      molecules involved in angiogenesis signaling pathways and are overexpressed in
      many angiogenic processes. Therefore, they represent specific biomarkers not only
      to monitor disease progression but also to rationally design targeted
      nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to
      specific integrins have been widely utilized to provide ligand-mediated targeting
      capabilities to small molecules, peptides, proteins, and antibodies, as well as
      to drug/imaging agent-containing nanomedicines, with the final aim of maximizing
      their therapeutic index. Within this review, we aim to cover recent and relevant
      examples of different integrin-assisted nanosystems including polymeric
      nanoconstructs, liposomes, and inorganic nanoparticles applied in drug/gene
      therapy as well as imaging and theranostics. We will also critically address the
      overall benefits of integrin-targeting.

PMID- 28502769
TI  - Tracing the Enterococci from Paleozoic Origins to the Hospital.
AB  - We examined the evolutionary history of leading multidrug resistant hospital
      pathogens, the enterococci, to their origin hundreds of millions of years ago.
      Our goal was to understand why, among the vast diversity of gut flora,
      enterococci are so well adapted to the modern hospital environment. Molecular
      clock estimation, together with analysis of their environmental distribution,
      phenotypic diversity, and concordance with host fossil records, place the origins
      of the enterococci around the time of animal terrestrialization, 425-500 mya.
      Speciation appears to parallel the diversification of hosts, including the rapid
      emergence of new enterococcal species following the End Permian Extinction. Major
      drivers of speciation include changing carbohydrate availability in the host gut.
      Life on land would have selected for the precise traits that now allow pathogenic
      enterococci to survive desiccation, starvation, and disinfection in the modern
      hospital, foreordaining their emergence as leading hospital pathogens.

PMID- 28502770
TI  - An Atomic Structure of the Human Spliceosome.
AB  - Mechanistic understanding of pre-mRNA splicing requires detailed structural
      information on various states of the spliceosome. Here we report the cryo
      electron microscopy (cryo-EM) structure of the human spliceosome just before exon
      ligation (the C* complex) at an average resolution of 3.76 A. The splicing factor
      Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an
      extended conformation, binds Prp8 and Cwc22, and is poised for selection of the
      3'-splice site. Remarkably, the intron lariat traverses through a positively
      charged central channel of RBM22; this unusual organization suggests mechanisms
      of intron recruitment, confinement, and release. The protein PRKRIP1 forms a 100
      A alpha helix linking the distant U2 snRNP to the catalytic center. A 35-residue
      fragment of the ATPase/helicase Prp22 latches onto Prp8, and the quaternary exon
      junction complex (EJC) recognizes upstream 5'-exon sequences and associates with
      Cwc22 and the GTPase Snu114. These structural features reveal important
      mechanistic insights into exon ligation.

PMID- 28502773
TI  - Phosphorylation of alphaB-crystallin in the myocardium: Analysis of relations
      with aging and cardiomyopathy.
AB  - Phosphorylation is a major post-translational modification of alphaB-crystallin
      (CryaB) and determines this protein's chaperone activity, intracellular
      distribution, translocation, and cytoprotective functions. Phosphorylation of
      CryaB manifests itself as either beneficial or deleterious consequences depending
      on the extent of phosphorylation and interaction with the cytoskeleton. Herein,
      for the first time, we compared the age-related alterations of the expression and
      phosphorylation (on Ser59: pS59) of CryaB in the myocardium of Wistar and
      senescence-accelerated OXYS rats. The latters, as we demonstrated here, develop
      cardiomyopathy by the age of 12 months against the background of hypertension.
      Rats at the age of 20 days, 3, 12, and 24 months were used. The expression of
      CryaB mRNA (studied by RT-PCR) and of the CryaB protein (analyzed by western
      blotting) increased with age in the myocardium of both Wistar and OXYS rats, but
      only at the age of 24 months did their levels become lower in OXYS rats.
      Phosphorylation of CryaB increased with age in all rats. There was no association
      of cardiomyopathy with the pS59-CryaB amount in the detergent-soluble fraction
      either. Moreover, immunostaining of the myocardium revealed that the amount of
      pS59-CryaB was greater in OXYS rats than in the control animals. This phenomenon
      was the result of translocation of pS59-CryaB from the detergent-soluble protein
      fraction to the detergent-insoluble one. The amount of pS59-CryaB in striated
      sarcomeres (detergent-insoluble) of the myocardium increased with age in both
      strains but faster in the myocardium of OXYS rats, and its accumulation preceded
      the development of cardiomyopathy. Translocation of phosphorylated CryaB to
      sarcomeres affects functional and structural properties (of cardiomyocytes) that
      are crucial for contractile function and myofibrillar organization and may be an
      important component of an endogenous mechanism of aging of the myocardium.

PMID- 28502772
TI  - Representations of Novelty and Familiarity in a Mushroom Body Compartment.
AB  - Animals exhibit a behavioral response to novel sensory stimuli about which they
      have no prior knowledge. We have examined the neural and behavioral correlates of
      novelty and familiarity in the olfactory system of Drosophila. Novel odors elicit
      strong activity in output neurons (MBONs) of the alpha'3 compartment of the
      mushroom body that is rapidly suppressed upon repeated exposure to the same odor.
      This transition in neural activity upon familiarization requires odor-evoked
      activity in the dopaminergic neuron innervating this compartment. Moreover,
      exposure of a fly to novel odors evokes an alerting response that can also be
      elicited by optogenetic activation of alpha'3 MBONs. Silencing these MBONs
      eliminates the alerting behavior. These data suggest that the alpha'3 compartment
      plays a causal role in the behavioral response to novel and familiar stimuli as a
      consequence of dopamine-mediated plasticity at the Kenyon cell-MBONalpha'3
      synapse.

PMID- 28502774
TI  - Latitudinal and age-specific patterns of larval mortality in the damselfly Lestes
      sponsa: Senescence before maturity?
AB  - Latitudinal differences in life history traits driven by differences in seasonal
      time constraints have been widely documented. Yet, latitudinal patterns in (age
      specific) mortality rates have been poorly studied. Here, we studied latitudinal
      differences in pre-adult age-specific mortality patterns in the strictly
      univoltine damselfly Lestes sponsa. We compared individuals from three latitudes
      reared from the egg stage in the laboratory at temperatures and photoperiods
      simulating those at the latitude of origin (main experiment) and under common
      garden conditions at a fixed temperature and photoperiod (supplementary
      experiment). Results from the main experiment showed that the high-latitude
      population exhibited higher mortality rates than the central and southern
      populations, likely reflecting a cost of their faster development. Age-specific
      mortality patterns, also indicated higher ageing rates in the high-latitude
      compared to the low-latitude population, which likely had a genetic basis. The
      strong within-population variation in hatching dates in the low-latitude
      population caused variation in mortality rates; individuals that hatched later
      showed higher mortality rates presumably due to their shorter development times
      compared to larvae that hatched earlier. In both experiments, larvae from all
      three latitudes showed accelerated mortality rates with age, which is consistent
      with a pattern of senescence before adulthood.

PMID- 28502771
TI  - Metabolic Phenotypes of Response to Vaccination in Humans.
AB  - Herpes zoster (shingles) causes significant morbidity in immune compromised hosts
      and older adults. Whereas a vaccine is available for prevention of shingles, its
      efficacy declines with age. To help to understand the mechanisms driving vaccinal
      responses, we constructed a multiscale, multifactorial response network (MMRN) of
      immunity in healthy young and older adults immunized with the live attenuated
      shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody,
      plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses.
      The MMRN reveals striking associations between orthogonal datasets, such as
      transcriptomic and metabolomics signatures, cell populations, and cytokine
      levels, and identifies immune and metabolic correlates of vaccine immunity.
      Networks associated with inositol phosphate, glycerophospholipids, and sterol
      metabolism are tightly coupled with immunity. Critically, the sterol regulatory
      binding protein 1 and its targets are key integrators of antibody and T
      follicular cell responses. Our approach is broadly applicable to study human
      immunity and can help to identify predictors of efficacy as well as mechanisms
      controlling immunity to vaccination.

PMID- 28502775
TI  - On the functional order of binocular rivalry and blind spot filling-in.
AB  - Binocular rivalry is an important phenomenon for understanding the mechanisms of
      visual awareness. Here we assessed the functional locus of binocular rivalry
      relative to blind spot filling-in, which is thought to transpire in V1, thus
      providing a reference point for assessing the locus of rivalry. We conducted two
      experiments to explore the functional order of binocular rivalry and blind spot
      filling-in. Experiment 1 examined if the information filled-in at the blind spot
      can engage in rivalry with a physical stimulus at the corresponding location in
      the fellow eye. Participants' perceptual reports showed no difference between
      this condition and a condition where filling-in was precluded by presenting the
      same stimuli away from the blind spot, suggesting that the rivalry process is not
      influenced by any filling-in that might occur. In Experiment 2, we presented the
      fellow eye's stimulus directly in rivalry with the 'inducer' stimulus that
      surrounds the blind spot, and compared it with two control conditions away from
      the blind spot: one involving a ring physically identical to the inducer, and one
      involving a disc that resembled the filled-in percept. Perceptual reports in the
      blind spot condition resembled those in the 'ring' condition, more than those in
      the latter, 'disc' condition, indicating that a perceptually suppressed inducer
      does not engender filling-in. Thus, our behavioral data suggest binocular rivalry
      functionally precedes blind spot filling-in. We conjecture that the neural
      substrate of binocular rivalry suppression includes processing stages at or
      before V1.

PMID- 28502776
TI  - Dried plum and chokeberry ameliorate d-galactose-induced aging in mice by
      regulation of Pl3k/Akt-mediated Nrf2 and Nf-kB pathways.

PMID- 28502777
TI  - Peripheral muscle fatigue in hospitalised geriatric patients is associated with
      circulating markers of inflammation.
AB  - Geriatric patients with acute infection show increased muscle weakness and
      fatigability but the relative contribution of central and peripheral factors is
      unclear. Hospitalised patients with acute infection (82+/-6years, N=10) and
      community-dwelling controls (76+/-6years, N=19) sustained a maximal voluntary
      isometric contraction of the M. Adductor Pollicis until strength dropped to 50%
      of its maximal value. Voluntary muscle activation (VA) was assessed before and at
      the end of the fatigue protocol using twitch interpolation method and muscle
      activity was monitored using surface electromyography. Twenty-five circulating
      inflammatory biomarkers were determined. At pre-fatigue, no significant
      difference in VA was found between groups. VA decreased to similar levels (~50%)
      at the end of the fatigue protocol with no association with inflammatory
      biomarkers. In geriatric patients, muscle activity decreased significantly
      (p<0.05) during the fatigue protocol, whereas it increased in the controls
      (time*group interaction p<0.05). The decrease in muscle activity was
      significantly related to higher levels of inflammation. Although slower muscle
      contraction and relaxation were significantly related to higher levels of
      inflammation, no statistical differences were found between groups. Our results
      confirm that muscle activity is significantly altered in older patients with
      acute infection and that local processes are involved.

PMID- 28502768
TI  - Lysosomal enzyme replacement therapies: Historical development, clinical
      outcomes, and future perspectives.
AB  - Lysosomes and lysosomal enzymes play a central role in numerous cellular
      processes, including cellular nutrition, recycling, signaling, defense, and cell
      death. Genetic deficiencies of lysosomal components, most commonly enzymes, are
      known as "lysosomal storage disorders" or "lysosomal diseases" (LDs) and lead to
      lysosomal dysfunction. LDs broadly affect peripheral organs and the central
      nervous system (CNS), debilitating patients and frequently causing fatality.
      Among other approaches, enzyme replacement therapy (ERT) has advanced to the
      clinic and represents a beneficial strategy for 8 out of the 50-60 known LDs.
      However, despite its value, current ERT suffers from several shortcomings,
      including various side effects, development of "resistance", and suboptimal
      delivery throughout the body, particularly to the CNS, lowering the therapeutic
      outcome and precluding the use of this strategy for a majority of LDs. This
      review offers an overview of the biomedical causes of LDs, their socio-medical
      relevance, treatment modalities and caveats, experimental alternatives, and
      future treatment perspectives.

PMID- 28502778
TI  - The joint association of insulin sensitivity and physical activity on the
      skeletal muscle mass and performance in community-dwelling older adults.
AB  - BACKGROUND: Many well-known risk factors that may lead to sarcopenia are already
      discovered. However, their combined effects on sarcopenia components remain
      unclear. This study aims to explore the joint association of physical activity
      and insulin sensitivity on skeletal muscle mass and performance of Taiwanese
      elder people from a metropolitan community. METHODS: The study sample involved
      844 elders who were examined through dual energy X-ray absorptiometry and who
      underwent tests for fasting blood glucose and serum insulin level. The
      homeostasis model assessment (HOMA-IR) equation estimated insulin sensitivity.
      Physical performance was assessed by grip strength and walking speed, while
      physical activity status was assessed using the questionnaires answered by the
      participants. RESULTS: After multivariate adjustment, the mean height- and weight
      adjusted skeletal muscle indexes (SMIs) for old people in the highest tertile of
      HOMA-IR values were 6.7kg/m2 and 27.9%, respectively, which were significantly
      lower than those of old people in the lowest tertile of HOMA-IR values. Compared
      with physically active elders with the lowest tertile of HOMA-IR values, the
      physically inactive elders with the highest tertile of HOMA-IR values had
      significantly low means in the height-adjusted SMI, weight-adjusted SMI, gait
      speed, and grip strength (0.25kg/m2 [p=0.0046], 0.97% [p=0.0068], 0.24m/s
      [p<0.0001], and 2.37kg [p=0.0085], respectively). CONCLUSION: Our study
      identified the joint associations of physical inactivity and low insulin
      sensitivity level on SMI, gait speed, and grip strength. The results provide new
      information for sarcopenia screening program that target elders who are
      predisposed to have physical dysfunction in old adults living in community.

PMID- 28502779
TI  - Microeukaryote community in a partial nitritation reactor prior to anammox and an
      insight into the potential of ciliates as performance bioindicators.
AB  - An in-depth, long-term, multidisciplinary study was conducted in order to study
      the microeukaryote community in a partial nitritation (PN) reactor prior to
      anammox. The PN reactor operated with moving bed biofilm reactor (MBBR)
      technology, using plastic supports (carriers) for biofilm development. The
      microeukaryote community from the biofilm (BF) and the surrounding media (mixed
      liquor or ML) were analysed separately. Despite the physicochemical conditions
      under which the PN-MBBR operated (an average of 305.9+/-117mg TAN l-1 and 328.4+/
      131.9mg N-NO2- l-1), up to 24 microeukaryotic taxa were observed by microscope.
      Microeukaryote species showed an uneven distribution in the PN-MBBR, thus
      suggesting the existence of two habitats: the BF, preferred by species with
      specific structures for adhering to a substrate, such as the stalked Peritrichia,
      and the ML, preferred by free-swimming or non-substrate dependent species. The
      results indicated that most ciliate population dynamics mainly responded to the
      nitrous acid and free ammonia concentrations and, to a lesser extent, to sCOD
      values. In the BF, variations in the population of Epistylis camprubii and
      Opercularia coarctata suggest the existence of competition between these species
      due to niche overlap. A V4 18S rDNA molecular survey (Illumina) was carried out
      for some samples with the aim of obtaining maximum coverage of the main eukaryote
      species that were microscopically detected throughout the study. The diversity
      and abundance data provided by both detection methods were compared. The study
      helped identify broader tolerance ranges of the microeukaryote taxa to the
      physicochemical parameters analysed.

PMID- 28502780
TI  - Biodegradation of endocrine disruptors in urban wastewater using Pleurotus
      ostreatus bioreactor.
AB  - The white rot fungus Pleurotus ostreatus HK 35, which is also an edible
      industrial mushroom commonly cultivated in farms, was tested in the degradation
      of typical representatives of endocrine disrupters (EDCs; bisphenol A, estrone,
      17beta-estradiol, estriol, 17alpha-ethinylestradiol, triclosan and 4-n
      nonylphenol); its degradation efficiency under model laboratory conditions was
      greater than 90% within 12 days and better than that of another published strain
      P. ostreatus 3004. A spent mushroom substrate from a local farm was tested for
      its applicability in various batch and trickle-bed reactors in degrading EDCs in
      model fortified and real communal wastewater. The reactors were tested under
      various regimes including a pilot-scale trickle-bed reactor, which was finally
      tested at a wastewater treatment plant. The result revealed that the spent
      substrate is an efficient biodegradation agent, where the fungus was usually able
      to remove about 95% of EDCs together with suppression of the estrogenic activity
      of the sample. The results showed the fungus was able to operate in the presence
      of bacterial microflora in wastewater without any substantial negative effects on
      the degradation abilities. Finally, a pilot-scale trickle-bed reactor was
      installed in a wastewater treatment plant and successfully operated for 10days,
      where the bioreactor was able to remove more than 76% of EDCs present in the
      wastewater.

PMID- 28502782
TI  - Time-Resolved X-Ray Solution Scattering Reveals the Structural Photoactivation of
      a Light-Oxygen-Voltage Photoreceptor.
AB  - Light-oxygen-voltage (LOV) receptors are sensory proteins controlling a wide
      range of organismal adaptations in multiple kingdoms of life. Because of their
      modular nature, LOV domains are also attractive for use as optogenetic actuators.
      A flavin chromophore absorbs blue light, forms a bond with a proximal cysteine
      residue, and induces changes in the surroundings. There is a gap of knowledge on
      how this initial signal is relayed further through the sensor to the effector
      module. To characterize these conformational changes, we apply time-resolved X
      ray scattering to the homodimeric LOV domain from Bacillus subtilis YtvA. We
      observe a global structural change in the LOV dimer synchronous with the
      formation of the chromophore photoproduct state. Using molecular modeling, this
      change is identified as splaying apart and relative rotation of the two monomers,
      which leads to an increased separation at the anchoring site of the effector
      modules.

PMID- 28502783
TI  - Evolution, expression analysis, and functional verification of Catharanthus
      roseus RLK1-like kinase (CrRLK1L) family proteins in pear (Pyrus bretchneideri).
AB  - The Catharanthus roseus RLK1-like kinase (CrRLK1L) family is involved in multiple
      processes during plant growth. However, little is known about CrRLK1L in the wood
      of the pear fruit tree Pyrus bretchneideri. In this study, 26 CrRLK1L gene
      members were identified in pear and were grouped into six subfamilies according
      to phylogenetic analyses. Evolutionary analysis indicated that recent whole
      genome duplication (WGD) and dispersed gene duplications may contribute to the
      expansion of the CrRLK1L gene family in pear. Moreover, tissue-specific
      expression analyses suggested that CrRLK1Ls are involved in the development of
      various pear tissues. Subsequent qRT-PCR analyses indicated that CrRLK1Ls might
      play important roles in pollen tube growth. Finally, experiments with antisense
      oligonucleotides (ASO) demonstrated that PbrCrRLK1L26 have functions in pollen
      tube elongation and that PbrCrRLK1L3 regulates pollen tube rupture. These results
      will be useful for elaborating the biological roles of CrRLK1Ls in pear growth
      and development.

PMID- 28502784
TI  - Liposome loaded phage cocktail: Enhanced therapeutic potential in resolving
      Klebsiella pneumoniae mediated burn wound infections.
AB  - BACKGROUND: Klebsiella pneumoniae is one of the predominant pathogens in burn
      wound infections, and prevalence of multidrug resistant strains has further
      complicated the situation. An increased interest in phage therapy as a means of
      combating infection has been accruing in recent years. In order to overcome the
      drawbacks associated with phage therapy, the present study was conducted to
      evaluate the potential of liposomes as a delivery vehicle for phage in the
      treatment of burn wound infection. METHODS: Burn wound infection with Klebsiella
      pneumoniae B5055 was established in BALB/c mice. The therapeutic efficacy of free
      phage cocktail in comparison to liposome entrapped phage cocktail in resolving
      the course of burn wound infection in mice was evaluated. RESULTS: The results
      depicted that mice treated with liposomal entrapped phage cocktail showed higher
      reduction in bacterial load in blood and major organs. This was accompanied with
      faster resolution of the entire infection process as compared to non-liposomal
      free phage cocktail. The liposomes increased phage retention time in vivo thus
      potentiating efficacy. Liposomal phage preparation was able to protect all the
      test animals from death even when there was a delay of 24h in instituting the
      therapy. CONCLUSION: The results showed the potential of liposome entrapped phage
      cocktail for treating Klebsiella pneumoniae mediated infections. Thus, this
      strategy can serve as an effective approach for treating Klebsiella mediated burn
      wound infections in individuals who do not respond to conventional antibiotic
      therapy.

PMID- 28502781
TI  - Checks and balances: The glucocorticoid receptor and NFKB in good times and bad.
AB  - Mutual regulation and balance between the endocrine and immune systems facilitate
      an organism's stress response and are impaired following chronic stress or
      prolonged immune activation. Concurrent alterations in stress physiology and
      immunity are increasingly recognized as contributing factors to several stress
      linked neuropsychiatric disorders including depression, anxiety, and post
      traumatic stress disorder. Accumulating evidence suggests that impaired balance
      and crosstalk between the glucocorticoid receptor (GR) and nuclear factor kappa
      light-chain-enhancer of activated B cells (NFkappaB) - effectors of the stress
      and immune axes, respectively - may play a key role in mediating the harmful
      effects of chronic stress on mood and behavior. Here, we first review the
      molecular mechanisms of GR and NFkappaB interactions in health, then describe
      potential shifts in the GR-NFkappaB dynamics in chronic stress conditions within
      the context of brain circuitry relevant to neuropsychiatric diseases.
      Furthermore, we discuss developmental influences and sex differences in the
      regulation of these two transcription factors.

PMID- 28502785
TI  - CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.
AB  - Immunotherapy is a promising field that harnesses the power of the immune system
      as a therapeutic agent for cancer treatment. Beneficial outcomes shown in
      patients with non-small cell lung cancer (NSCLC) and malignant pleural
      mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined
      with impressive responses obtained in a cohort of patients with NSCLC following
      checkpoint blockade therapy, lays a strong foundation to promote effector immune
      responses in these patients. One such approach being investigated is
      administration of tumor antigen-targeted T cells with transduction of a chimeric
      antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell
      antitumor effector function and have gained momentum to investigate in solid
      tumors based on recent successes of clinical trials treating patients with B-cell
      hematologic malignancies. This review summarizes target antigens for CAR T-cell
      therapy that are being investigated in preclinical studies and clinical trials
      for both NSCLC and MPM patients. We discuss the rationale for combination
      immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the
      challenges and strategies for overcoming the obstacles facing translation of CAR
      T-cell therapy to solid tumors.

PMID- 28502786
TI  - Randomized Evaluation of Cognitive-Behavioral Therapy and Graded Exercise Therapy
      for Post-Cancer Fatigue.
AB  - CONTEXT: Cancer-related fatigue is prevalent and disabling. When persistent and
      unexplained, it is termed post-cancer fatigue (PCF). Cognitive behavioral therapy
      (CBT) and graded exercise therapy (GET) may improve symptoms and functional
      outcomes. OBJECTIVES: To evaluate the outcomes of a randomized controlled trial,
      which assigned patients with post-cancer fatigue to education, or 12 weeks of
      integrated cognitive-behavioral therapy (CBT) and graded exercise therapy (GET).
      METHODS: Three months after treatment for breast or colon cancer, eligible
      patients had clinically significant fatigue, no comorbid medical or psychiatric
      conditions that explained the fatigue, and no evidence of recurrence. The CBT/GET
      arm included individually tailored consultations at approximately two weekly
      intervals. The education arm included a single visit with clinicians describing
      the principles of CBT/GET and a booklet. The primary outcome was clinically
      significant improvement in self-reported fatigue (Somatic and Psychological
      HEalth REport 0-12), designated a priori as greater than one SD of improvement in
      fatigue score. The secondary outcome was associated improvement in function (role
      limitation due to physical health problems-36-Item Short Form Health Survey 0
      100) comparing baseline, end treatment (12 weeks), and follow-up (24 weeks).
      RESULTS: There were 46 patients enrolled, including 43 women (94%), with a mean
      age of 51 years. Fatigue severity improved in all subjects from a mean of 5.2 (+/
      3.1) at baseline to 3.9 (+/-2.8) at 12 weeks, suggesting a natural history of
      improvement. Clinically significant improvement was observed in 7 of 22 subjects
      in the intervention group compared with 2 of 24 in the education group (P < 0.05,
      chi2). These subjects also had improvement in functional status compared with
      nonresponders (P < 0.01, t-test). CONCLUSION: Combined CBT/GET improves fatigue
      and functional outcomes for a subset of patients with post-cancer fatigue.
      Further studies to improve the response rate and the magnitude of the benefit are
      warranted.

PMID- 28502787
TI  - No association detected between seven common variants in the CDKAL1 gene and
      gestational glycemic traits.
AB  - Elevated plasma glucose levels in pregnancy increase adverse pregnancy outcomes.
      Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1)
      has been shown to be involved in insulin secretion in pancreatic beta cells. In
      this study, we investigated the impact of genetic variants in CDKAL1 on plasma
      glucose, insulin values, beta cell function and insulin resistance in the fasted
      state as well as plasma glucose 1 h after the consumption of a 50-g oral glucose
      load between 24 and 28 weeks of pregnancy among 929 unrelated pregnant Han
      Chinese women. Seven common variants previously reported to associate with
      diabetes were genotyped. Insulin resistance and beta cell function were assessed
      by homeostasis model assessment. The genetic impacts were analyzed using analysis
      of variance and analysis of covariance. The results showed that there was no
      significant association between any of the seven variants and those gestational
      glycemic traits. Therefore, this study suggests that the seven common variants in
      CDKAL1 are not significant factors for the variations of several gestational
      glycemic traits in the Han Chinese population. However, further well-designed
      studies with larger sample size, more ethnic groups and more CDKAL1 variants are
      required to validate the association between CDKAL1 and gestational glycemic
      traits.

PMID- 28502788
TI  - Reply.

PMID- 28502790
TI  - Crystallographic and biochemical characterization of the dimeric architecture of
      site-2 protease.
AB  - Regulated intramembrane proteolysis by members of the site-2 protease family
      (S2P) is an essential signal transduction mechanism conserved from bacteria to
      humans. There is some evidence that extra-membranous domains, like PDZ and CBS
      domains, regulate the proteolytic activity of S2Ps and that some members act as
      dimers. Here we report the crystal structure of the regulatory CBS domain pair of
      S2P from Archaeoglobus fulgidus, AfS2P, in the apo and nucleotide-bound form in
      complex with a specific nanobody from llama. Cross-linking and SEC-MALS analyses
      show for the first time the dimeric architecture of AfS2P both in the membrane
      and in detergent micelles. The CBS domain pair dimer (CBS module) displays an
      unusual head-to-tail configuration and nucleotide binding triggers no major
      conformational changes in the magnesium-free state. In solution, MgATP drives
      monomerization of the CBS module. We propose a model of the so far unknown
      architecture of the transmembrane domain dimer and for a regulatory mechanism of
      AfS2P that involves the interaction of positively charged arginine residues
      located at the cytoplasmic face of the transmembrane domain with the negatively
      charged phosphate groups of ATP moieties bound to the CBS domain pairs. Binding
      of MgATP could promote opening of the CBS module to allow lateral access of the
      globular cytoplasmic part of the substrate.

PMID- 28502789
TI  - Supported lipid bilayer platforms to probe cell mechanobiology.
AB  - Mammalian and bacterial cells sense and exert mechanical forces through the
      process of mechanotransduction, which interconverts biochemical and physical
      signals. This is especially important in contact-dependent signaling, where
      ligand-receptor binding occurs at cell-cell or cell-ECM junctions. By virtue of
      occurring within these specialized junctions, receptors engaged in contact
      dependent signaling undergo oligomerization and coupling with the cytoskeleton as
      part of their signaling mechanisms. While our ability to measure and map
      biochemical signaling within cell junctions has advanced over the past decades,
      physical cues remain difficult to map in space and time. Recently, supported
      lipid bilayer (SLB) technologies have emerged as a flexible platform to mimic and
      perturb cell-cell and cell-ECM junctions, allowing one to study membrane receptor
      mechanotransduction. Changing the lipid composition and underlying substrate
      tunes bilayer fluidity, and lipid and ligand micro- and nano-patterning spatially
      control positioning and clustering of receptors. Patterning metal gridlines
      within SLBs confines lipid mobility and introduces mechanical resistance. Here we
      review fundamental SLB mechanics and how SLBs can be engineered as tunable cell
      substrates for mechanotransduction studies. Finally, we highlight the impact of
      this work in understanding the biophysical mechanisms of cell adhesion. This
      article is part of a Special Issue entitled: Interactions between membrane
      receptors in cellular membranes edited by Kalina Hristova.

PMID- 28502791
TI  - Single-Strand Consensus Sequencing Reveals that HIV Type but not Subtype
      Significantly Impacts Viral Mutation Frequencies and Spectra.
AB  - A long-standing question of human immunodeficiency virus (HIV) genetic variation
      and evolution has been whether differences exist in mutation rate and/or mutation
      spectra among HIV types (i.e., HIV-1 versus HIV-2) and among HIV groups (i.e.,
      HIV-1 groups M-P and HIV-2 groups A-H) and HIV-1 Group M subtypes (i.e., subtypes
      A-D, F-H, and J-K). To address this, we developed a new single-strand consensus
      sequencing assay for the determination of HIV mutation frequencies and spectra
      using the Illumina sequencing platform. This assay enables parallel and
      standardized comparison of HIV mutagenesis among various viral vectors with lower
      background error than traditional methods of Illumina library preparation. We
      found significant differences in viral mutagenesis between HIV types but
      intriguingly no significant differences among HIV-1 Group M subtypes. More
      specifically, HIV-1 exhibited higher transition frequencies than HIV-2, due
      mostly to single G-to-A mutations and (to a lesser extent) G-to-A hypermutation.
      These data suggest that HIV-2 RT exhibits higher fidelity during viral
      replication, and taken together, these findings demonstrate that HIV type but not
      subtype significantly affects viral mutation frequencies and spectra. These
      differences may inform antiviral and vaccine strategies.

PMID- 28502793
TI  - Salt-Mediated Oligomerization of the Mouse Prion Protein Monitored by Real-Time
      NMR.
AB  - The prion protein forms beta-rich soluble oligomers in vitro at pH4 in the
      presence of physiological concentrations of salt. In the absence of salt,
      oligomerization and misfolding do not take place in an experimentally tractable
      timescale. While it is well established that a lowering of pH facilitates
      misfolding and oligomerization of this protein, the role of salt remains poorly
      understood. Here, solution-state NMR was used to probe perturbations in the
      monomeric mouse prion protein structure immediately upon salt addition, prior to
      the commencement of the oligomerization reaction. The weak binding of salt at
      multiple sites dispersed all over the monomeric protein causes a weak and non
      specific perturbation of structure throughout the protein. The only significant
      perturbation occurs in the loop between helix 2 and 3 in and around the partially
      buried K193-E195 salt bridge. The disruption of this key electrostatic
      interaction is the earliest detectable change in the monomer before any major
      conformational change occurs and appears to constitute the trigger for the
      commencement of misfolding and oligomerization. Subsequently, the kinetics of
      monomer loss, due to oligomerization, was monitored at the individual residue
      level. The oligomerization reaction was found to be rate-limited by association
      and not conformational change, with an average reaction order of 2.6 across
      residues. Not surprisingly, salt accelerated the oligomerization kinetics, in a
      non-specific manner, by electrostatic screening of the highly charged monomers at
      acidic pH. Together, these results allowed a demarcation of the specific and non
      specific effects of salt on prion protein misfolding and oligomerization.

PMID- 28502792
TI  - Drug Binding Poses Relate Structure with Efficacy in the MU Opioid Receptor.
AB  - The MU-opioid receptor (MOPr) is a clinically important G protein-coupled
      receptor that couples to Gi/o proteins and arrestins. At present, the receptor
      conformational changes that occur following agonist binding and activation are
      poorly understood. This study has employed molecular dynamics simulations to
      investigate the binding mode and receptor conformational changes induced by
      structurally similar opioid ligands of widely differing intrinsic agonist
      efficacy, norbuprenorphine, buprenorphine, and diprenorphine. Bioluminescence
      resonance energy transfer assays for Gi activation and arrestin-3 recruitment in
      human embryonic kidney 293 cells confirmed that norbuprenorphine is a high
      efficacy agonist, buprenorphine a low efficacy agonist, and diprenorphine an
      antagonist at the MOPr. Molecular dynamics simulations revealed that these
      ligands adopt distinct binding poses and engage different subsets of residues,
      despite sharing a common morphinan scaffold. Notably, norbuprenorphine interacted
      with sodium ion-coordinating residues W2936.48 and N1503.35, whilst buprenorphine
      and diprenorphine did not. Principal component analysis of the movements of the
      receptor transmembrane domains showed that the buprenorphine-bound receptor
      occupied a distinct set of conformations to the norbuprenorphine-bound receptor.
      Addition of an allosteric sodium ion caused the receptor and ligand to adopt an
      inactive conformation. The differences in ligand-residue interactions and
      receptor conformations observed here may underlie the differing efficacies for
      cellular signalling outputs for these ligands.

PMID- 28502794
TI  - miR-125a-5p Modulates Phenotypic Switch of Vascular Smooth Muscle Cells by
      Targeting ETS-1.
AB  - MicroRNAs are key regulators of vascular smooth muscle cells (VSMCs) phenotypic
      switch, one of the main events responsible for bare metal in-stent restenosis
      after percutaneous coronary intervention. miR-125a-5p is an important modulator
      of differentiation, proliferation, and migration in different cell types;
      however, its role in VSMCs is still unknown. The aim of this study was to
      evaluate the role of miR-125a-5p in VSMCs phenotypic switch. Our results suggest
      that miR-125a-5p is highly expressed in VSMCs, but it is down-regulated after
      vascular injury in vivo. Its overexpression is sufficient to reduce VSMCs
      proliferation and migration, and it is able to promote the expression of
      selective VSMCs markers such as alpha smooth muscle actin, myosin heavy chain 11,
      and smooth muscle 22 alpha. Interestingly, miR-125a-5p directly targets ETS-1, a
      transcription factor implicated in cell proliferation and migration and is
      crucial in PDGF-BB pathway in VSMCs. Thus, miR-125a-5p in this context inhibits
      PDGF-BB pathway and is therefore a potential regulator of VSMCs phenotypic
      switch.

PMID- 28502795
TI  - Multi-scale, tailor-made heart simulation can predict the effect of cardiac
      resynchronization therapy.
AB  - BACKGROUND: The currently proposed criteria for identifying patients who would
      benefit from cardiac resynchronization therapy (CRT) still need to be optimized.
      A multi-scale heart simulation capable of reproducing the electrophysiology and
      mechanics of a beating heart may help resolve this problem. The objective of this
      retrospective study was to test the capability of patient-specific simulation
      models to reproduce the response to CRT by applying the latest multi-scale heart
      simulation technology. METHODS AND RESULTS: We created patient-specific heart
      models with realistic three-dimensional morphology based on the clinical data
      recorded before treatment in nine patients with heart failure and conduction
      block treated by biventricular pacing. Each model was tailored to reproduce the
      surface electrocardiogram and hemodynamics of each patient in formats similar to
      those used in clinical practice, including electrocardiography (ECG),
      echocardiography, and hemodynamic measurements. We then performed CRT simulation
      on each heart model according to the actual pacing protocol and compared the
      results with the clinical data. CRT simulation improved the ECG index and
      diminished wall motion dyssynchrony in each patient. These results, however, did
      not correlate with the actual response. The best correlation was obtained between
      the maximum value of the time derivative of ventricular pressure (dP/dtmax) and
      the clinically observed improvement in the ejection fraction (EF) (r=0.94,
      p<0.01). CONCLUSIONS: By integrating the complex pathophysiology of the heart,
      patient-specific, multi-scale heart simulation could successfully reproduce the
      response to CRT. With further verification, this technique could be a useful tool
      in clinical decision making.

PMID- 28502797
TI  - Understanding the Potential Interethnic Difference in Rosuvastatin
      Pharmacokinetics.
AB  - Here we address the potential difference in rosuvastatin pharmacokinetics in
      Asians vs. whites. Our prospective study, reported in this issue, shows no ethnic
      difference when all subjects are wild-type for OATP1B1 and BCRP. We argue that
      although our study may be under powered to prove no ethnic difference, and that
      further confirmatory study is required, the virtual clinical study analysis, also
      reported in this issue, does not contradict the results of our prospective
      clinical study and that previous retrospective analysis of clinical studies does
      not include enough relevant subjects to conclude that wild-type OATP1B1 and BCRP
      do still demonstrate ethnic differences.

PMID- 28502796
TI  - In vivo reprogramming for heart regeneration: A glance at efficiency,
      environmental impacts, challenges and future directions.
AB  - Replacing dying or diseased cells of a tissue with new ones that are converted
      from patient's own cells is an attractive strategy in regenerative medicine. In
      vivo reprogramming is a novel strategy that can circumvent the hurdles of
      autologous/allogeneic cell injection therapies. Interestingly, studies have
      demonstrated that direct injection of cardiac transcription factors or specific
      miRNAs into the infarct border zone of murine hearts following myocardial
      infarction converts resident cardiac fibroblasts into functional cardiomyocytes.
      Moreover, in vivo cardiac reprogramming not only drives cardiac tissue
      regeneration, but also improves cardiac function and survival rate after
      myocardial infarction. Thanks to the influence of cardiac microenvironment and
      the same developmental origin, cardiac fibroblasts seem to be more amenable to
      reprogramming toward cardiomyocyte fate than other cell sources (e.g. skin
      fibroblasts). Thus, reprogramming of cardiac fibroblasts to functional induced
      cardiomyocytes in the cardiac environment holds great promises for induced
      regeneration and potential clinical purposes. Application of small molecules in
      future studies may represent a major advancement in this arena and
      pharmacological reprogramming would convey reprogramming technology to the
      translational medicine paradigm. This study reviews accomplishments in the field
      of in vitro and in vivo mouse cardiac reprogramming and then deals with
      strategies for the enhancement of the efficiency and quality of the process.
      Furthermore, it discusses challenges ahead and provides suggestions for future
      research. Human cardiac reprogramming is also addressed as a foundation for
      possible application of in vivo cardiac reprogramming for human heart
      regeneration in the future.

PMID- 28502798
TI  - Structure of a soluble epoxide hydrolase identified in Trichoderma reesei.
AB  - Epoxide hydrolases (EHs) are enzymes that have high biotechnological interest for
      the fine and transformation industry. Several of these enzymes have
      enantioselectivity, which allows their application in the separation of
      enantiomeric mixtures of epoxide substrates. Although two different families of
      EHs have been described, those that have the alpha/beta-hidrolase fold are the
      most explored for biotechnological purpose. These enzymes are functionally very
      well studied, but only few members have three-dimensional structures
      characterised. Recently, a new EH from the filamentous fungi Trichoderma reseei
      (TrEH) has been discovered and functionally studied. This enzyme does not have
      high homology to any other EH structure and have an enatiopreference for (S)-(-)
      isomers. Herein we described the crystallographic structure of TrEH at 1.7A
      resolution, which reveals features of its tertiary structure and active site.
      TrEH has a similar fold to the other soluble epoxide hydrolases and has the two
      characteristic hydrolase and cap domains. The enzyme is predominantly monomeric
      in solution and has also been crystallised as a monomer in the asymmetric unit.
      Although the catalytic residues are conserved, several other residues of the
      catalytic groove are not, and might be involved in the specificity for substrates
      and in the enantioselectivy of this enzyme. In addition, the determination of the
      crystallographic structure of TrEH might contribute to the rational site direct
      mutagenesis to generate an even more stable enzyme with higher efficiency to be
      used in biotechnological purposes.

PMID- 28502799
TI  - Proteomics and metabolomics-driven pathway reconstruction of mung bean for
      nutraceutical evaluation.
AB  - Mung bean is a legume crop which has a various health-promoting effects. Although
      rich flavonoids are reported to be responsible for its biological activities,
      little is known about other nutrients that may potentiate the activities. To
      obtain information on mung bean nutritional properties, gel-free/label-free
      proteomic analysis and metabolomic profiling were combined. Pathway
      reconstruction detected that amino acid metabolism is more active in flesh. Coat
      contained wider variety of lipids and phenolic acids/flavonoids than flesh. Among
      the compounds detected in coat, sphingolipids, arachidonic acid, and
      prostaglandin E2 are compounds which are related to immune response induction.
      Furthermore, identification of prostaglandin F2alpha added scientific support to
      empirical validity of mung bean usage. The abundance of bioactive compounds such
      as naringenin, which can be metabolized into vitexin, varied among cultivars.
      These results suggest that lipids together with flavonoids might be potential
      responsible compounds for biological activity of mung bean coat and flesh.

PMID- 28502800
TI  - MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human
      Vitiligo.
AB  - Vitiligo is a common chronic skin disorder characterized by loss of epidermal
      melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic,
      environmental, and biochemical causes, but the exact molecular mechanisms of
      vitiligo development and progression, particularly those related to metabolic
      control, are poorly understood. In this study we characterized the human vitiligo
      cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing,
      targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211,
      a known metabolic switch in nonpigmented melanoma cells, was severely down
      regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo
      patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were
      reciprocally up-regulated. microRNA-211 binds to PGC1-alpha 3' untranslated
      region locus and represses it. Although mitochondrial numbers were constant,
      mitochondrial complexes I, II, and IV and respiratory responses were defective in
      vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen
      consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in
      lipid and metabolite profiles, and increased reactive oxygen species production
      observed in vitiligo cells appear to be partly due to abnormal regulation of
      microRNA-211 and its target genes. These genes represent potential biomarkers and
      therapeutic targets in human vitiligo.

PMID- 28502801
TI  - Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging.
AB  - Loss of fine skin patterning is a sign of both aging and photoaging. Studies
      investigating the genetic contribution to skin patterning offer an opportunity to
      better understand a trait that influences both physical appearance and risk of
      keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association
      studies of a measure of skin pattern (microtopography score) damage in 1,671 twin
      pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We
      identified that rs185146 near SLC45A2 is associated with a skin aging trait at
      genome-wide significance (P = 4.1 * 10-9); to our knowledge this is previously
      unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P =
      8.8 * 10-13) and rs4268748 near MC1R (P = 1.2 * 10-15). At all three loci we
      highlight putative functionally relevant SNPs. There are a number of red hair/low
      pigmentation alleles of MC1R; we found that together these MC1R alleles explained
      4.1% of variance in skin pattern damage. We also show that skin aging and
      reported experience of sunburns was proportional to the degree of penetrance for
      red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin
      aging and confirmed previous findings, showing that pigmentation is a critical
      determinant of skin aging.

PMID- 28502802
TI  - Topically Delivered Tumor Necrosis Factor-alpha-Targeted Gene Regulation for
      Psoriasis.

PMID- 28502804
TI  - WDR79/TCAB1 plays a conserved role in the control of locomotion and ameliorates
      phenotypic defects in SMA models.
AB  - SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal
      muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to
      progressive paralysis and death. Although SMN is required in every cell for
      proper RNA metabolism, the reason why its loss is especially critical in the
      motor system is still unclear. SMA genetic models have been employed to identify
      several modifiers that can ameliorate the deficits induced by SMN depletion. Here
      we focus on WDR79/TCAB1, a protein important for the biogenesis of several RNA
      species that has been shown to physically interact with SMN in human cells. We
      show that WDR79 depletion results in locomotion defects in both Drosophila and
      Caenorhabditis elegans similar to those elicited by SMN depletion. Consistent
      with this observation, we find that SMN overexpression rescues the WDR79 loss-of
      function phenotype in flies. Most importantly, we also found that WDR79
      overexpression ameliorates the locomotion defects induced by SMN depletion in
      both flies and worms. Our results collectively suggest that WDR79 and SMN play
      evolutionarily conserved cooperative functions in the nervous system and suggest
      that WDR79/TCAB1 may have the potential to modify SMA pathogenesis.

PMID- 28502803
TI  - Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE
      expressing mice following traumatic brain injury.
AB  - Traumatic brain injury (TBI) is strongly linked to an increased risk of
      developing dementia, including chronic traumatic encephalopathy and possibly
      Alzheimer's disease (AD). APOEepsilon4 allele of human Apolipoprotein E (APOE)
      gene is the major genetic risk factor for late onset AD and has been associated
      with chronic traumatic encephalopathy and unfavorable outcome following TBI. To
      determine if there is an APOE isoform-specific response to TBI we performed
      controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4
      isoforms. Following injury, we used several behavior paradigms to test for
      anxiety and learning and found that APOE3 and APOE4 targeted replacement mice
      demonstrate cognitive impairments following moderate TBI. Transcriptional
      profiling 14days following injury revealed a significant effect of TBI, which was
      similar in both genotypes. Significantly upregulated by injury in both genotypes
      were mRNA expression and protein level of ABCA1 transporter and APOJ, but not
      APOE. To identify gene-networks correlated to injury and APOE isoform, we
      performed Weighted Gene Co-expression Network Analysis. We determined that the
      network mostly correlated to TBI in animals expressing both isoforms is immune
      response with major hub genes including Trem2, Tyrobp, Clec7a and Cd68. We also
      found a significant increase of TREM2, IBA-1 and GFAP protein levels in the
      brains of injured mice. We identified a network representing myelination that
      correlated significantly with APOE isoform in both injury groups. This network
      was significantly enriched in oligodendrocyte signature genes, such as Mbp and
      Plp1. Our results demonstrate unique and distinct gene networks at this acute
      time point for injury and APOE isoform, as well as a network driven by APOE
      isoform across TBI groups.

PMID- 28502805
TI  - Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic
      model of tauopathy.
AB  - Tau exists as six closely related protein isoforms in the adult human brain.
      These are generated from alternative splicing of a single mRNA transcript and
      they differ in the absence or presence of two N-terminal and three or four
      microtubule binding domains. Typically all six isoforms have been considered
      functionally similar. However, their differential involvement in particular
      tauopathies raises the possibility that there may be isoform-specific differences
      in physiological function and pathological role. To explore this, we have
      compared the phenotypes induced by the 0N3R and 0N4R isoforms in Drosophila.
      Expression of the 3R isoform causes more profound axonal transport defects and
      locomotor impairments, culminating in a shorter lifespan than the 4R isoform. In
      contrast, the 4R isoform leads to greater neurodegeneration and impairments in
      learning and memory. Furthermore, the phosphorylation patterns of the two
      isoforms are distinct, as is their ability to induce oxidative stress. These
      differences are not consequent to different expression levels and are suggestive
      of bona fide physiological differences in isoform biology and pathological
      potential. They may therefore explain isoform-specific mechanisms of tau-toxicity
      and the differential susceptibility of brain regions to different tauopathies.

PMID- 28502806
TI  - Treadmill exercise delays the onset of non-motor behaviors and striatal pathology
      in the CAG140 knock-in mouse model of Huntington's disease.
AB  - Depression, cognitive impairments, and other neuropsychiatric disturbances are
      common during the prodromal phase of Huntington's disease (HD) well before the
      onset of classical motor symptoms of this degenerative disorder. The purpose of
      this study was to examine the potential impact of physical activity in the form
      of exercise on a motorized treadmill on non-motor behavioral features including
      depression-like behavior and cognition in the CAG140 knock-in (KI) mouse model of
      HD. The CAG140 KI mouse model has a long lifespan compared to other HD rodent
      models with HD motor deficits emerging after 12months of age and thus provides
      the opportunity to investigate early life interventions such as exercise on
      disease progression. Motorized treadmill running was initiated at 4weeks of age
      (1h per session, 3 times per week) and continued for 6months. Non-motor behaviors
      were assessed up to 6months of age and included analysis of depression-like
      behavior (using the tail-suspension and forced-swim tests) and cognition (using
      the T-maze and object recognition tests). At both 4 and 6months of age, CAG140 KI
      mice displayed significant depression-like behavior in the forced swim and tail
      suspension tests and cognitive impairment by deficits in reversal relearning in
      the T-maze test. These deficits were not evident in mice engaged in treadmill
      running. In addition, exercise restored striatal dopamine D2 receptor expression
      and dopamine neurotransmitter levels both reduced in sedentary HD mice. Finally,
      we examined the pattern of striatal expression of mutant huntingtin (mHTT)
      protein and showed that the number and intensity of immunohistochemical staining
      patterns of intranuclear aggregates were significantly reduced with exercise.
      Altogether these findings begin to address the potential impact of lifestyle and
      early intervention such as exercise on modifying HD progression.

PMID- 28502807
TI  - Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy
      for decreasing neuronal proteotoxicity and aging.
AB  - Accumulation of toxic protein aggregates in the nerve cells is a hallmark of
      neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to
      improve neuronal proteostasis have a direct impact on promoting neuronal health
      and forestalling age-related decline in brain function. Autophagy is a lysosomal
      degradative pathway pivotal for neuronal protein quality control. Different types
      of autophagic mechanisms participate in protein handling in neurons.
      Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles
      to the lysosomes for destruction, while chaperone-mediated autophagy (CMA)
      degrades specific soluble cytosolic proteins delivered to the lysosomes by
      chaperones. Dysfunctions in macroautophagy and CMA contribute to proteo- and
      neuro-toxicity associated with neurodegeneration and aging. Thus, augmenting or
      preserving both autophagic mechanisms pose significant benefits in delaying
      physiological and pathological neuronal demises. Recently, life-style
      interventions that modulate metabolite ketone bodies, energy intake by caloric
      restriction and energy expenditure by exercise have shown to enhance both
      autophagy and brain health. However, to what extent these interventions affect
      neuronal autophagy to promote brain fitness remains largely unclear. Here, we
      review the functional connections of how macroautophagy and CMA are affected by
      ketone bodies, caloric restriction and exercise in the context of
      neurodegeneration. A concomitant assessment of yeast Saccharomyces cerevisiae is
      performed to reveal the conserved nature of such autophagic responses to
      substrate perturbations. In doing so, we provide novel insights and integrated
      evidence for a potential adjuvant therapeutic strategy to intervene in the
      neuronal decline in neurodegenerative diseases by controlling both macroautophagy
      and CMA fluxes favorably.

PMID- 28502808
TI  - Series: Pragmatic trials and real world evidence: Paper 3. Patient selection
      challenges and consequences.
AB  - This paper addresses challenges of identifying, enrolling, and retaining
      participants in a trial conducted within a routine care setting. All patients who
      are potential candidates for the treatments in routine clinical practice should
      be considered eligible for a pragmatic trial. To ensure generalizability, the
      recruited sample should have a similar distribution of the treatment effect
      modifiers as the target population. In practice, this can be best achieved by
      including-within the selected sites-all patients without further selection. If
      relevant heterogeneity between subgroups is expected, increasing the relative
      proportion of the subgroup of patients in the heterogeneous trial could be
      considered (oversampling) or a separate trial in this subgroup can be planned.
      Selection will nevertheless occur. Low enrollment and loss to follow-up can
      introduce selection and can jeopardize validity as well as generalizability.
      Pragmatic trials are conducted in clinical practice rather than in a dedicated
      research setting, which could reduce recruitment rates. However, if a trial poses
      a minimal burden to the physician and the patient and routine clinical practice
      is maximally adhered to, the participation rate may be high and loss to follow-up
      will not be a specific problem for pragmatic trials.

PMID- 28502809
TI  - Series: Pragmatic trials and real world evidence: Paper 4. Informed consent.
AB  - The GetReal consortium of the Innovative Medicines Initiative aims to develop
      strategies to incorporate real-world evidence earlier into the drug life cycle to
      better inform health care decision makers on the comparative risks and benefits
      of new drugs. Pragmatic trials are currently explored as a means to generate such
      evidence in routine care settings. The traditional informed consent model for
      randomized clinical trials has been argued to pose substantial hurdles to the
      practicability of pragmatic trials: it would lead to recruitment difficulties,
      reduced generalizability of the results, and selection bias. The present article
      analyzes these challenges and discusses four proposed alternative informed
      consent models: integrated consent, targeted consent, broadcast consent, and a
      waiver of consent. These alternative consent models each aim at overcoming
      operational and methodological challenges, while still providing patients all the
      relevant information they need to make informed decisions. Each consent model,
      however, relies on different attitudes toward the principle of respect for
      persons and the related duty to inform patients as well as represents different
      views on whether the common good demands moral duties from patients. Such
      normative consequences of modifying consent requirements should be at least
      acknowledged and ought to be assessed in light of the validity of empirical
      claims.

PMID- 28502810
TI  - Series: Pragmatic trials and real world evidence: Paper 6. Outcome measures in
      the real world.
AB  - Results from pragmatic trials should reflect the comparative treatment effects
      encountered in patients in real-life clinical practice to guide treatment
      decisions. Therefore, pragmatic trials should focus on outcomes that are relevant
      to patients, clinical practice, and treatment choices. This sixth article in the
      series (see Box) discusses different types of outcomes and their suitability for
      pragmatic trials, design choices for measuring these outcomes, and their
      implications and challenges. Measuring outcomes in pragmatic trials should not
      interfere with real-world clinical practice to ensure generalizability of trial
      results, and routinely collected outcomes should be prioritized. Typical outcomes
      include mortality, morbidity, functional status, well-being, and resource use.
      Surrogate endpoints are typically avoided as primary outcome. It is important to
      measure outcomes over a relevant time horizon and obtain valid and precise
      results. As pragmatic trials are often open label, a less subjective outcome can
      reduce bias. Methods that decrease bias or enhance precision of the results, such
      as standardization and blinding of outcome assessment, should be considered when
      a high risk of bias or high variability is expected. The selection of outcomes in
      pragmatic trials should be relevant for decision making and feasible in terms of
      executing the trial in the context of interest. Therefore, this should be
      discussed with all stakeholders as early as feasible to ensure the relevance of
      study results for decision making in clinical practice and the ability to perform
      the study.

PMID- 28502811
TI  - Series: Pragmatic trials and real world evidence: Paper 2. Setting, sites, and
      investigator selection.
AB  - This second article in the series on pragmatic trials describes the challenges in
      selection of sites for pragmatic clinical trials and the impact on validity,
      precision, and generalizability of the results. The selection of sites is an
      important factor for the successful execution of a pragmatic trial and impacts
      the extent to which the results are applicable to future patients in clinical
      practice. The first step is to define usual care and understand the heterogeneity
      of sites, patient demographics, disease prevalence and country choice. Next,
      specific site characteristics are important to consider such as interest in the
      objectives of the trial, the level of research experience, availability of
      resources, and the expected number of eligible patients. It can be advisable to
      support the sites with implementing the trial-related activities and minimize the
      additional burden that the research imposes on routine clinical practice. Health
      care providers should be involved in an early phase of protocol development to
      generate engagement and ensure an appropriate selection of sites with patients
      who are representative of the future drug users.

PMID- 28502812
TI  - Series: Pragmatic trials and real world evidence: Paper 7. Safety, quality and
      monitoring.
AB  - OBJECTIVE: Pragmatic trials offer the opportunity to obtain real-life data on the
      relative effectiveness and safety of a treatment before or after market
      authorization. This is the penultimate paper in a series of eight, describing the
      impact of design choices on the practical implementation of pragmatic trials.
      STUDY DESIGN AND SETTING: This paper focuses on the practical challenges of
      collecting and reporting safety data and of monitoring trial conduct while
      maintaining routine clinical care practice. CONCLUSION: Current ICH guidance
      recommends that all serious adverse events and all drug-related events must be
      reported in an interventional trial. In line with current guidance, we propose a
      risk-based approach to the collection of non-drug-related non-serious adverse
      events and even serious events not related to treatment based on the risk profile
      of the medicine/class in the patient population of interest. Different options
      available to support the collection and reporting of safety data while minimizing
      study-related follow-up visits are discussed. A risk-based approach to monitoring
      trial conduct is also discussed, highlighting the difference in the balance of
      risks likely to occur in a pragmatic trial compared to traditional clinical
      trials and the careful consideration that must be given to the mitigation and
      management of these risks to maintain routine care.

PMID- 28502813
TI  - The Clinical Relevance of Studies on Borrelia burgdorferi Persisters.

PMID- 28502814
TI  - Breathless: Beta Thalassemia Major.

PMID- 28502815
TI  - Using Sutton's Law: Yellow Nail Syndrome.

PMID- 28502816
TI  - Death and Dignity: Exploring Physicians' Responsibilities After a Patient's
      Death.

PMID- 28502817
TI  - Concussion.
AB  - Concussion has been recognized as a clinical entity for more than 1000 years.
      Throughout the 20th century it was studied extensively in boxers, but it did not
      pique the interest of the general population because it is the accepted goal of
      the boxer to inflict such an injury on their opponent. In 2002, however, the
      possibility that repetitive concussions could result in chronic brain damage and
      a progressive neurologic disorder was raised by a postmortem evaluation of a
      retired player in the most popular sports institution in the United States, the
      National Football League. Since that time concussion has been a frequent topic of
      conversation in homes, schools, and on television and has become a major focus of
      sports programs in communities and schools at all levels. Now all 50 states, the
      District of Columbia, and the National Collegiate Athletic Association have
      enacted laws and rules to protect the athlete.

PMID- 28502818
TI  - Renal Function Considerations for Stroke Prevention in Atrial Fibrillation.
AB  - Renal impairment increases risk of stroke and systemic embolic events and
      bleeding in patients with atrial fibrillation. Direct oral anticoagulants (DOACs)
      have varied dependence on renal elimination, magnifying the importance of
      appropriate patient selection, dosing, and periodic kidney function monitoring.
      In randomized controlled trials of nonvalvular atrial fibrillation, DOACs were at
      least as effective and associated with less bleeding compared with warfarin. Each
      direct oral anticoagulant was associated with reduced risk of stroke and systemic
      embolic events and major bleeding compared with warfarin in nonvalvular atrial
      fibrillation patients with mild or moderate renal impairment. Renal function
      decrease appears less impacted by DOACs, which are associated with a better risk
      benefit profile than warfarin in patients with decreasing renal function over
      time. Limited data address the risk-benefit profile of DOACs in patients with
      severe impairment or on dialysis.

PMID- 28502819
TI  - Functional relevance of miRNAs in premature ageing.
AB  - Ageing is a complex biological process characterized by the progressive loss of
      biological fitness due to the accumulation of macromolecular and cellular damage
      that affects most living organisms. Moreover, ageing is an important risk factor
      for many pathologies, including cardiovascular diseases, neurological disorders,
      and cancer. However, the ageing rate can be modulated by genetic, nutritional,
      and pharmacological factors, highlighting the concept of "ageing plasticity".
      Progeroid syndromes are a group of rare genetic diseases that resemble many
      characteristics of physiological ageing. Accordingly, studies on these diseases
      have been very useful for gaining mechanistic insights in ageing biology. In
      recent years, a great effort has been made in ageing research and several works
      have confirmed that geromiRs, the growing subgroup of miRNAs implicated in
      ageing, are able to modulate organismal lifespan. However, very little is still
      known about the impact of miRNA in premature ageing. In this review, we will
      address the functional relevance of this class of small non-coding RNAs in the
      regulation of the hallmarks of progeroid syndromes. In addition, we will discuss
      the potential strategies for managing progeria based on geromiR modulation.

PMID- 28502820
TI  - Cancer-Incidence, prevalence and mortality in the oldest-old. A comprehensive
      review.
AB  - Chronic health conditions are commonplace in older populations. The process of
      aging impacts many of the world's top health concerns. With the average life
      expectancy continuing to climb, understanding patterns of morbidity in aging
      populations has become progressively more important. Cancer is an age-related
      disease, whose risk has been proven to increase with age. Limited information is
      published about the epidemiology of cancer and the cancer contribution to
      mortality in the 85+ age group, often referred to as the oldest-old. In this
      review, we perform a comprehensive assessment of the most recent (2011-2016)
      literature on cancer prevalence, incidence and mortality in the oldest-old. The
      data shows cancer prevalence and cancer incidence increases until ages 85-89,
      after which the rates decrease into 100+ ages. However the number of overall
      cases has steadily increased over time due to the rise in population. Cancer
      mortality continues to increase after age 85+. This review presents an overview
      of plausible associations between comorbidity, genetics and age-related
      physiological effects in relation to cancer risk and protection. Many of these
      age-related processes contribute to the lowered risk of cancer in the oldest-old,
      likewise other certain health conditions may "protect" from cancer in this age
      group.

PMID- 28502822
TI  - Anti-inflammatory properties of the stem bark from the herbal drug Vitex
      peduncularis Wall. ex Schauer and characterization of its polyphenolic profile.
AB  - Vitex spp. have been reported as constituents of herbal preparations, namely
      Vitex peduncularis, commonly used in Asian countries. Unlike other species
      extensively investigated, reports on the biological activities and chemical
      profile of V. peduncularis are still scarce. In this work, the polyphenolic
      profile of V. peduncularis stem bark was unveiled, revealing a high content of
      apigenin and luteolin derivatives. More than 20 polyphenols were identified and
      quantitated for the first time, including C-rhamnosyl flavones infrequently
      reported. Regarding potential anti-inflammatory properties, the methanolic
      extract of the stem bark significantly reduced the levels of NO in macrophages,
      which may be a consequence of scavenging effect upon *NO. Significant inhibition
      of phospholipase A2 activity was also noted. Consequently, the therapeutic
      applicability of this edible plant is also broadened due to the anti-inflammatory
      properties found.

PMID- 28502824
TI  - Human group 2 innate lymphoid cells do not express the IL-5 receptor.

PMID- 28502821
TI  - SASP regulation by noncoding RNA.
AB  - Noncoding RNAs (ncRNAs), including micro (mi)RNAs, long noncoding (lnc)RNAs, and
      circular (circ)RNAs, control specific gene expression programs by regulating
      transcriptional, post-transcriptional, and post-translational processes. Through
      their broad influence on protein expression and function, ncRNAs have been
      implicated in virtually all cellular processes such as proliferation, senescence,
      quiescence, differentiation, apoptosis, and the stress and immune responses.
      Senescence is a cellular phenotype associated with the physiologic decline of
      aging and with age-related pathologies. Besides their characteristic terminal
      growth arrest and differential gene expression programs, senescent cells are
      known to secrete potent pro-inflammatory, angiogenic, and tissue-remodeling
      factors. This important trait, known as the senescence-associated secretory
      phenotype (SASP), influences many biological processes such as tissue repair and
      regeneration, tumorigenesis, and the aging-associated pro-inflammatory state.
      Here, we review the microRNAs, lncRNAs, and circRNAs that influence the
      production of SASP factors and discuss the rising interest in SASP-regulatory
      ncRNAs as diagnostic and therapeutic targets.

PMID- 28502825
TI  - Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency
      with allogeneic hematopoietic stem cell transplantation.

PMID- 28502826
TI  - Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary
      Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.
AB  - BACKGROUND: Ovarian tumors, although uncommon in children, can retain endocrine
      function that disrupts normal feedback mechanisms leading to amenorrhea.
      Inheritance of germline DICER1 mutations can lead to increased risk for
      development of ovarian Sertoli-Leydig cell tumors (SLCTs). CASE: We report, to
      our knowledge, the first case of secondary amenorrhea due to elevated inhibin B
      levels in a female adolescent with an ovarian SLCT. SUMMARY AND CONCLUSION:
      Ovarian tumors should be included in the differential diagnosis for pediatric
      patients who present with menstrual irregularities. Early evaluation of the
      hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case
      also emphasizes the need for testing for DICER1 mutations in pediatric patients
      with ovarian SLCTs.

PMID- 28502823
TI  - NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and
      childhood asthma-implications for home environmental intervention in asthma
      prevention and management.
AB  - Environmental exposures have been recognized as critical in the initiation and
      exacerbation of asthma, one of the most common chronic childhood diseases. The
      National Institute of Allergy and Infectious Diseases; National Institute of
      Environmental Health Sciences; National Heart, Lung, and Blood Institute; and
      Merck Childhood Asthma Network sponsored a joint workshop to discuss the current
      state of science with respect to the indoor environment and its effects on the
      development and morbidity of childhood asthma. The workshop included US and
      international experts with backgrounds in allergy/allergens, immunology, asthma,
      environmental health, environmental exposures and pollutants, epidemiology,
      public health, and bioinformatics. Workshop participants provided new insights
      into the biologic properties of indoor exposures, indoor exposure assessment, and
      exposure reduction techniques. This informed a primary focus of the workshop: to
      critically review trials and research relevant to the prevention or control of
      asthma through environmental intervention. The participants identified important
      limitations and gaps in scientific methodologies and knowledge and proposed and
      prioritized areas for future research. The group reviewed socioeconomic and
      structural challenges to changing environmental exposure and offered
      recommendations for creative study design to overcome these challenges in trials
      to improve asthma management. The recommendations of this workshop can serve as
      guidance for future research in the study of the indoor environment and on
      environmental interventions as they pertain to the prevention and management of
      asthma and airway allergies.

PMID- 28502828
TI  - Premature Ovarian Insufficiency: An Adolescent Series.
AB  - STUDY OBJECTIVE: To study the presentation and causes of premature ovarian
      insufficiency (POI) in adolescents. DESIGN: Retrospective notes review. SETTING:
      Tertiary referral outpatient clinic for pediatric and adolescent gynecology.
      PARTICIPANTS: Adolescents with POI. INTERVENTIONS: Standard POI evaluation. MAIN
      OUTCOME MEASURES: Age and clinical symptoms at presentation, causative factors
      for POI, if identified. RESULTS: We identified 22 girls with POI, with a mean age
      of 15.6 years. Eight of them presented with delayed puberty, 3 with primary
      amenorrhea, and the remainder presented with either irregular bleeding (n = 9) or
      secondary amenorrhea (n = 2). For those who presented with delayed puberty, only
      3 were found to have a sex chromosome abnormality. A clear cause for the POI was
      identified in 3 further cases. CONCLUSION: Although POI in adolescents
      traditionally is associated with primary amenorrhea and delayed puberty, a
      proportion of girls will present with irregular bleeding that might be mistaken
      for expected menstrual disturbances of puberty, thus delaying the diagnosis. We
      identified a clear cause for POI in 6 cases. Although there were no familial
      cases of POI, it remains a possibility that genetic reasons might be involved in
      the pathogenesis.

PMID- 28502827
TI  - Provider and Health System Factors Associated with Usage of Long-Acting
      Reversible Contraception in Adolescents.
AB  - STUDY OBJECTIVE: Long-acting reversible contraception (LARC) is recommended as
      first-line contraception for adolescents. Surveys of primary care providers
      suggest that physician and clinic factors might influence LARC counseling, but
      their effect on usage is unknown. Our objective was to explore provider and
      clinic characteristics associated with LARC usage in adolescents. DESIGN,
      SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted a
      cross-sectional study of 5363 women ages 15-21 years receiving primary care
      within a large health system in Massachusetts in 2015. We used data abstracted
      from electronic medical records to characterize rates of LARC usage. We analyzed
      the association of provider (specialty, degree, gender, resident status, LARC
      credentialing) and clinic (Title X funding, onsite LARC provision, onsite
      obstetrician-gynecologist) factors with adolescents' LARC usage using
      multivariate logistic regression. RESULTS: Overall, 3.4% (95% confidence interval
      [CI], 2.9-3.9) of adolescents were documented as currently using a LARC method.
      Older adolescents were significantly more likely to use a LARC method (adjusted
      odds ratio, 2.41; 95% CI, 1.62-3.58 for women ages 20-21 years compared with ages
      15-17 years). Adolescents whose primary care provider was a resident were
      significantly more likely to use a LARC method (adjusted odds ratio, 1.65; 95%
      CI, 1.02-2.68). Provider specialty, degree, gender, onsite LARC provision, and
      onsite obstetrician-gynecologist were not significantly associated with LARC
      usage in adolescents. CONCLUSION: Being older and having a primary care provider
      early in their training increased the odds of LARC usage among adolescents in a
      large Massachusetts health system. Across primary care specialties, educating
      providers about the appropriate uses of LARC methods in nulliparous adolescents
      might facilitate LARC usage.

PMID- 28502829
TI  - Primary Ovarian Fibrosarcoma-An Unusual Tumor in an Adolescent: Case Report and
      Review of the Pediatric Literature.
AB  - BACKGROUND: Primary ovarian fibrosarcomas are rare and usually observed in
      perimenopausal and postmenopausal women. To our knowledge, to date, there are
      only 3 reports of ovarian fibrosarcoma in childhood and adolescence in the
      English-language literature. In this report, we aimed to present to our
      knowledge, the first pediatric case with advanced stage primary ovarian
      fibrosarcoma and to compare with previous cases. CASE: A 14-year-old teenage girl
      was admitted because of a giant abdominal mass. Imaging techniques revealed a
      giant heterogeneous and vascular ovarian mass. Salpingo-oophorectomy along with
      staging procedures were performed. Pathologic examination confirmed grade III
      ovarian fibrosarcoma with severe nuclear atypia and high mitotic count. Because
      of pulmonary metastasis, she received 4 courses of adjuvant combination
      chemotherapy (Ewing protocol). The patient withstood the treatment well and is
      disease-free at 2 years of follow-up. CONCLUSION: Fibrosarcoma of the ovary is an
      uncommon neoplasm with poor prognosis. To our knowledge, the presented patient is
      the first pediatric case with advanced staged primary ovarian fibrosarcoma to be
      treated with surgery and adjuvant chemotherapy.

PMID- 28502830
TI  - With me or against me: Tumor suppressor and drug resistance activities of SAMHD1.
AB  - Sterile alpha motif and histidine/aspartic acid domain-containing protein 1
      (SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated
      deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular
      dNTP homoeostasis. Mutations in SAMHD1 have been associated with the
      hyperinflammatory disease Aicardi-Goutieres syndrome (AGS). SAMHD1 also limits
      cells' permissiveness to infection with diverse viruses, including human
      immunodeficiency virus (HIV-1), and controls endogenous retroviruses. Increasing
      evidence supports the role of SAMHD1 as a tumor suppressor. However, SAMHD1 also
      can act as a resistance factor to nucleoside-based chemotherapies by hydrolyzing
      their active triphosphate metabolites, thereby reducing response of various
      malignancies to these anticancer drugs. Hence, informed cancer therapies must
      take into account the ambiguous properties of SAMHD1 as both an inhibitor of
      uncontrolled proliferation and a resistance factor limiting the efficacy of
      anticancer treatments. Here, we provide evidence that SAMHD1 is a double-edged
      sword for patients with acute myelogenous leukemia (AML). Our time-dependent
      analyses of The Cancer Genome Atlas (TCGA) AML cohort indicate that high
      expression of SAMHD1, even though it critically limits the efficacy of high-dose
      ara-C therapy, might be associated with more favorable disease progression.

PMID- 28502831
TI  - A 12-week randomized clinical trial investigating the potential for sucralose to
      affect glucose homeostasis.
AB  - The discovery of gut sweet taste receptors has led to speculations that non
      nutritive sweeteners, including sucralose, may affect glucose control. A double
      blind, parallel, randomized clinical trial, reported here and previously
      submitted to regulatory agencies, helps to clarify the role of sucralose in this
      regard. This was primarily an out-patient study, with 4-week screening, 12-week
      test, and 4-week follow-up phases. Normoglycemic male volunteers (47) consumed
      ~333.3 mg encapsulated sucralose or placebo 3x/day at mealtimes. HbA1c, fasting
      glucose, insulin, and C-peptide were measured weekly. OGTTs were conducted in
      clinic overnight, following overnight fasting twice during screening phase, twice
      during test phase, and once at follow-up. Throughout the study, glucose, insulin,
      C-peptide and HbA1c levels were within normal range. No statistically significant
      differences between sucralose and placebo groups in change from baseline for
      fasting glucose, insulin, C-peptide and HbA1c, no clinically meaningful
      differences in time to peak levels or return towards basal levels in OGTTs, and
      no treatment group differences in mean glucose, insulin, or C-peptide AUC change
      from baseline were observed. The results of other relevant clinical trials and
      studies of gastrointestinal sweet taste receptors are compared to these findings.
      The collective evidence supports that sucralose has no effect on glycemic
      control.

PMID- 28502833
TI  - Overactive Bladder Is Strongly Associated With Frailty in Older Individuals.
AB  - OBJECTIVE: To understand the relationship between age, frailty, and overactive
      bladder (OAB). MATERIALS AND METHODS: This is a prospective study of individuals
      age >=65 years presenting to an academic urology practice between December 2015
      and July 2016. All patients had a Timed Up and Go Test (TUGT), a parsimonious
      measure of frailty, on intake, and were thereby categorized as fast (<=10
      seconds), intermediate (11-14 seconds), and slow (>=15 seconds). The TUGT and
      other clinical data were abstracted from the electronic medical record using
      direct queries. Logistic regression was used to examine the relationship between
      frailty and the diagnosis of OAB, adjusting for age, gender, and race. RESULTS:
      Our cohort included 201 individuals with and 1162 individuals without OAB.
      Individuals with OAB had slower TUGTs (13.7 +/- 7.9 seconds) than their non-OAB
      counterparts (10.9 +/- 5.2 seconds), P <.0001, with 32.3% and 11.0% of OAB and
      non-OAB individuals being categorized as slow, or frail. In multivariable
      analysis, slower TUGT was a significant predictor of OAB (adjusted odds ratio:
      3.0; 95% confidence interval: 2.0-4.8). Age was not independently associated with
      this diagnosis (P values >.05 for each age group). CONCLUSION: Patients with OAB
      are statistically significantly frailer than individuals seeking care for other
      non-oncologic urologic diagnoses. Frailty, when adjusted for age, race, and
      gender, is a statistically significant predictor of OAB. Furthermore, frailty
      should be considered when caring for older patients with OAB, and OAB should be
      assessed when caring for frail older patients.

PMID- 28502834
TI  - A Rare Case of Intravesical Angiomyofibroblastoma.
AB  - OBJECTIVE: To study the first reported case of intravesical angiomyofibroblastoma
      (AMFB). AMFB is an uncommon benign mesenchymal lesion, mostly described in the
      lower female genital tract, especially in the vulva and less commonly in the
      vagina. It is rarely seen in the male genital tract. The importance of this rare
      neoplasm is related to its potential mimicry of more infiltrative and
      prognostically less favorable lesions, such as aggressive angiomyxomas, that are
      found in the same anatomic area. METHODS: A 26-year-old man presented to us with
      hematuria. Investigations revealed an intraluminal polypoidal lesion of
      approximately 92 * 77 * 76 mm within the urinary bladder. Cystoscopy revealed a
      large well-circumscribed tumor with a pedicle, attached to the inferolateral wall
      of the bladder near the bladder neck. Open exploration and en bloc excision of
      the bladder mass was done. RESULTS: Histopathology and immunohistochemistry (IHC)
      confirmed the diagnosis of AMFB. CONCLUSION: AMFB presents as a well
      circumscribed superficial mass. Complete excision of the tumor for
      histopathologic and IHC examination is essential for diagnosis. This rare tumor
      shows morphologic similarity to some more aggressive tumors with less favorable
      outcome; hence, it needs to be differentiated from those. IHC is helpful but not
      always conclusive in the diagnosis of this rare neoplasm. This being the first
      ever reported case of intravesical AMFB bears a significant importance. Careful
      clinical assessment, operative management, and histopathologic examination are of
      utmost importance in making a precise diagnosis and management of the patient.

PMID- 28502832
TI  - Sexually dimorphic expression in developing and adult gonads shows an important
      role of gonadal soma-derived factor during sex differentiation in olive flounder
      (Paralichthys olivaceus).
AB  - Gonadal soma-derived factor (gsdf) is a new member of transforming growth factor
      beta (TGF-beta) superfamily. As a teleost- and gonad-specific growth factor, gsdf
      has been indicated to play an important role in early germ cell development.
      However, little is known about its significance in germ cell development of olive
      flounder (Paralichthys olivaceus). In the present study, a 1338 bp gsdf gene was
      isolated from P. olivaceus for the first time. Bioinformatic analysis revealed
      that the genomic structure and synteny relationship of gsdf in teleosts were
      conserved. Quantitative real-time PCR (qRT-PCR) showed that gsdf expressed before
      sex gonadal differentiation, and the expression level increased rapidly after
      initiation of sex differentiation in males. In adult individuals, the expression
      of gsdf was higher in testis than that in ovary (P<0.01). In situ hybridization
      (ISH) indicated that gsdf mRNA was detected in the somatic cells of both males
      and females, and also in the cytoplasm of oocytes. These results suggested that
      gsdf might play an important role as initial switches to promote testis
      differentiation and participate in early germ cell development, such as
      proliferation and differentiation of spermatogonia and oogonia in P. olivaceus.

PMID- 28502836
TI  - Selection of differently temporally regulated African swine fever virus promoters
      with variable expression activities and their application for transient and
      recombinant virus mediated gene expression.
AB  - African swine fever virus threatens pig production worldwide due to the lack of
      vaccines, for which generation of both deletion and insertion mutants is
      considered. For development of the latter, operational ASFV promoters of
      different temporal regulation and strengths are desirable. We therefore compared
      the capacities of putative promoter sequences from p72, CD2v, p30, viral DNA
      polymerase and U104L genes to mediate expression of luciferase from transfected
      plasmids after activation in trans, or p30-, DNA polymerase- and U104L promoters
      in cis, using respective ASFV recombinants. We identified sequences with promoter
      activities upstream the viral ORFs, and showed that they differ in both their
      expression intensity regulating properties and in their temporal regulation. In
      summary, p30 and DNA polymerase promoters are recommended for high level early
      regulated transgene expression. For late expression, the p72, CD2v and U104L
      promoter are suitable. The latter however, only if low level transgene expression
      is aimed.

PMID- 28502835
TI  - The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.
AB  - Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is
      characterized by endothelial dysfunction and nitric oxide (NO) depletion. The
      mechanisms underlying NO depletion as related to iAs exposure are not fully
      understood. The endogenous inhibitor of nitric oxide synthase, asymmetric
      dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations
      are regulated by proteins involved in its synthesis (arginine methyl transferase
      1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]).
      Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the
      ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to
      arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5MUM of arsenite for 24h. We
      proved that arsenite at 5MUM was able to decrease NO levels with an associated
      increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a
      decrease in DDAH-1 protein expression with 5MUM of arsenite compared to the
      control group. However, we did not observe significant differences in PRMT-1
      protein expression at any of the concentrations of arsenite employed. Finally,
      arsenite (2.5 and 5MUM) increased NADPH oxidase 4 protein levels compared with
      the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO
      depletion produced by arsenite, and that the mechanism is related to oxidative
      stress.

PMID- 28502837
TI  - Use of technology to facilitate physical activity in children with autism
      spectrum disorders: A pilot study.
AB  - Deficits in social behavior and communication skills are correlated with reduced
      gross motor skills in children with autism spectrum disorders (ASD). The
      ExerciseBuddy application (EB app) was designed to communicate these motor skills
      to those with ASD and integrates evidence-based practices such as visual support
      and video modeling supported by The National Professional Development Center on
      Autism Spectrum Disorders. The purpose of this study was to determine the
      effectiveness of the EB app in facilitating increased physiologic responses to
      physical activity via a continuous measurement of energy expenditure and heart
      rate versus practice-style teaching methods in children with ASD. Six children,
      ages 5 to 10years, diagnosed with ASD were recruited. Each participant performed
      a variety of locomotor or object control skills as defined by the Test of Gross
      Motor Development-2 once per week for 4weeks. Motor skills were communicated and
      demonstrated using either practice-style teaching methods or the instructional
      section of the EB app. Energy expenditure and heart rate were measured
      continuously during each 12-minute session. A Wilcoxon signed-rank test was
      performed to assess any differences between the use of the app and practice-style
      teaching methods. The use of the EB app elicited greater values for peak energy
      expenditure (p=0.043) and peak heart rate response (p=0.028) while performing
      locomotor skills but no differences were observed while performing object control
      skills. Similarities were observed with average physiologic responses between the
      use of the EB app and practice-style teaching methods. The use of the EB app may
      allow for a greater peak physiologic response during more dynamic movements and a
      similar average cardiovascular and metabolic response when compared to practice
      style teaching methods in children with ASD.

PMID- 28502838
TI  - Sleep quality and duration are associated with performance in maximal incremental
      test.
AB  - BACKGROUND AND OBJECTIVE: Inadequate sleep patterns may be considered a trigger
      to development of several metabolic diseases. Additionally, sleep deprivation and
      poor sleep quality can negatively impact performance in exercise training.
      However, the impact of sleep duration and sleep quality on performance during
      incremental maximal test performed by healthy men is unclear. Therefore, the
      purpose of the study was to analyze the association between sleep pattern
      (duration and quality) and performance during maximal incremental test in healthy
      male individuals. METHODS: A total of 28 healthy males volunteered to take part
      in the study. Sleep quality, sleep duration and physical activity were
      subjectively assessed by questionnaires. Sleep pattern was classified by sleep
      duration (>7h or <7h of sleep per night) and sleep quality according to the sum
      of measured points and/or scores by the Pittsburgh Sleep Quality Index (PSQI).
      Incremental exercise test was performed at 35 watts for untrained subjects, 70
      watts for physically active subjects and 105 watts for well-trained subjects.
      RESULTS: HRmax was correlated with sleep quality (r=0.411, p=0.030) and sleep
      duration (r=-0.430, p=0.022). Participants reporting good sleep quality presented
      higher values of Wmax, VO2max and lower values of HRmax when compared to
      participants with altered sleep. Regarding sleep duration, only Wmax was
      influenced by the amount of sleeping hours per night and this association
      remained significant even after adjustment by VO2max. CONCLUSION: Sleep duration
      and quality are associated, at least in part, with performance during maximal
      incremental test among healthy men, with losses in Wmax and HRmax. In addition,
      our results suggest that the relationship between sleep patterns and performance,
      mainly in Wmax, is independent of fitness condition.

PMID- 28502839
TI  - Predictors of failure after single faecal microbiota transplantation in patients
      with recurrent Clostridium difficile infection: results from a 3-year cohort
      study: authors' reply.

PMID- 28502840
TI  - The Perfect Transplant.

PMID- 28502841
TI  - Use of airway epithelial cell culture to unravel the pathogenesis and study
      treatment in obstructive airway diseases.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are considered as two
      distinct obstructive diseases. Both chronic diseases share a component of airway
      epithelial dysfunction. The airway epithelium is localized to deal with inhaled
      substances, and functions as a barrier preventing penetration of such substances
      into the body. In addition, the epithelium is involved in the regulation of both
      innate and adaptive immune responses following inhalation of particles, allergens
      and pathogens. Through triggering and inducing immune responses, airway
      epithelial cells contribute to the pathogenesis of both asthma and COPD. Various
      in vitro research models have been described to study airway epithelial cell
      dysfunction in asthma and COPD. However, various considerations and cautions have
      to be taken into account when designing such in vitro experiments. Epithelial
      features of asthma and COPD can be modelled by using a variety of disease-related
      invoking substances either alone or in combination, and by the use of primary
      cells isolated from patients. Differentiation is a hallmark of airway epithelial
      cells, and therefore models should include the ability of cells to differentiate,
      as can be achieved in air-liquid interface models. More recently developed in
      vitro models, including precision cut lung slices, lung-on-a-chip, organoids and
      human induced pluripotent stem cells derived cultures, provide novel state-of-the
      art alternatives to the conventional in vitro models. Furthermore, advanced
      models in which cells are exposed to respiratory pathogens, aerosolized
      medications and inhaled toxic substances such as cigarette smoke and air
      pollution are increasingly used to model e.g. acute exacerbations. These exposure
      models are relevant to study how epithelial features of asthma and COPD are
      affected and provide a useful tool to study the effect of drugs used in treatment
      of asthma and COPD. These new developments are expected to contribute to a better
      understanding of the complex gene-environment interactions that contribute to
      development and progression of asthma and COPD.

PMID- 28502842
TI  - Attentional capture in visual search: Capture and post-capture dynamics revealed
      by EEG.
AB  - Sometimes, salient-but-irrelevant objects (distractors) presented concurrently
      with a search target cannot be ignored and attention is involuntarily allocated
      towards the distractor first. Several studies have provided electrophysiological
      evidence for involuntary misallocations of attention towards a distractor, but
      much less is known about the mechanisms that are needed to overcome a
      misallocation and re-allocate attention towards the concurrently presented
      target. In our study, electrophysiological markers of attentional mechanisms
      indicate that (i) the distractor captures attention before the target is
      attended, (ii) a misallocation of attention is terminated actively (instead of
      attention fading passively), and (iii) the misallocation of attention towards a
      distractor delays the attention allocation towards the target (rather than just
      delaying some post-attentive process involved in response selection). This
      provides the most complete demonstration, to date, of the chain of attentional
      mechanisms that are evoked when attention is misguided and recovers from capture
      within a search display.

PMID- 28502843
TI  - Disentangling the effects of novelty, valence and trait anxiety in the bed
      nucleus of the stria terminalis, amygdala and hippocampus with high resolution 7T
      fMRI.
AB  - The hippocampus and amygdala exhibit sensitivity to stimulus novelty that is
      reduced in participants with inhibited temperament, which is related to trait
      anxiety. Although the bed nucleus of the stria terminalis (BNST) is highly
      connected to the amygdala and is implicated in anxiety, whether the BNST responds
      to novelty remains unstudied, as well as how trait anxiety may modulate this
      response. Additionally how novelty, stimulus negativity and trait anxiety
      interact to affect activity in these areas is also unclear. To address these
      questions, we presented participants with novel and repeated, fearful and neutral
      faces, while measuring brain activity via fMRI, and also assessed participants'
      self-reported trait anxiety. As the small size of the BNST makes assessing its
      activity at typical fMRI resolution difficult, we employed high resolution 7
      Tesla scanning. Our results replicate findings of novelty sensitivity that is
      independent of valence in the hippocampus. Our results also provide novel
      evidence for a BNST novelty response toward neutral, but not fearful faces. We
      also found that the novelty response in the hippocampus and BNST was blunted in
      participants with high trait anxiety. Additionally, we found left amygdala
      sensitivity to stimulus negativity that was blunted for high trait anxiety
      participants. These findings extend past research on the response to novel
      stimuli in the hippocampus and amygdala at high resolution, and are the first to
      demonstrate trait anxiety modulated novelty sensitivity in the BNST that is
      dependent on stimulus valence.

PMID- 28502844
TI  - A novel approach to map induced activation of neuronal networks using
      chemogenetics and functional neuroimaging in rats: A proof-of-concept study on
      the mesocorticolimbic system.
AB  - Linking neural circuit activation at whole-brain level to neuronal activity at
      cellular level remains one of the major challenges in neuroscience research. We
      set up a novel functional neuroimaging approach to map global effects of locally
      induced activation of specific midbrain projection neurons using chemogenetics
      (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology)
      combined with pharmacological magnetic resonance imaging (phMRI) in the rat
      mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic
      or mesocortical pathways, i.e. projections from the ventral tegmental area (VTA)
      to the nucleus accumbens (NAcc) or medial prefrontal cortex (mPFC), respectively,
      induced significant blood oxygenation level-dependent (BOLD) responses in areas
      with DREADD expression, but also in remote defined neural circuitry without
      DREADD expression. The time-course of brain activation corresponded with the
      behavioral output measure, i.e. locomotor (hyper)activity, in the mesolimbic
      pathway-targeted group. Chemogenetic activation specifically increased neuronal
      activity, whereas functional connectivity assessed with resting state functional
      MRI (rs-fMRI) remained stable. Positive and negative BOLD responses distinctively
      reflected simultaneous ventral pallidum activation and substantia nigra pars
      reticulata deactivation, respectively, demonstrating the concept of
      mesocorticolimbic network activity with concurrent activation of the direct and
      indirect pathways following stimulation of specific midbrain projection neurons.
      The presented methodology provides straightforward and widely applicable
      opportunities to elucidate relationships between local neuronal activity and
      global network activity in a controllable manner, which will increase our
      understanding of the functioning and dysfunctioning of large-scale neuronal
      networks in health and disease.

PMID- 28502846
TI  - Domains of physical activity and brain volumes: A population-based study.
AB  - Observational studies and intervention trials suggest that physical activity (PA)
      is beneficial for human brain morphology, especially in older individuals. Few
      population-based studies examined whether domain-specific PA is associated with
      brain volumes. Accordingly, we studied putative associations of PA during leisure
      time, sports and work with volumes of the hippocampus, the prefrontal cortex, the
      temporal lobe, gray matter (GM), white matter (WM) and total brain (TBV) after
      5.9 years by applying volumetric analysis and voxel-based morphometry (VBM) with
      SPM 8/VBM 8 to brain magnetic resonance imaging data of 834 participants (447
      women) aged 25 to 83 years from the population-based Study of Health in
      Pomerania. The Baecke questionnaire was used to assess domain-specific PA
      (Leisure time, Sport, and Work Index) at baseline. After correcting for multiple
      testing, volumetric analyses did not show any significant association of domain
      specific PA and volumes of the hippocampus, the prefrontal cortex, the temporal
      lobe, GM, WM and TBV. Multivariable-adjusted VBM analyses of the associations
      between PA domains with GM and WM volumes did not reveal any statistically
      significant results. Region of interest analyses revealed a statistically
      significant cluster of increased GM volume in the bilateral anterior cingulate
      cortex in association with PA during sports. In conclusion, the overall results
      contrast with the findings from previous studies that found significant
      associations between PA and brain volumes. In addition, it remains unclear
      whether a differential association exists between domains of PA and brain
      volumes. Thus, future studies with larger sample size and prospective design are
      needed to investigate potential domain-specific associations of PA with brain
      volumes.

PMID- 28502848
TI  - Exercise Training In Athletes With Heart Disease.
AB  - Exercise events and sport participation have increased over recent decades. The
      average age of sports participants has also increased with a potential parallel
      increase in the number of exercise participants with both occult and diagnosed
      cardiovascular disease (CVD). Habitual physical activity and exercise training
      reduce atherosclerotic CVD (ASCVD) risk in a curvilinear fashion by affecting
      multiple ASCVD risk factors. Nonetheless, exercise also increases the risk of
      sudden cardiac death in both young and adult individuals with occult CVD making
      it important to balance the risks and benefits of exercise and exercise training
      in these individuals. There are essentially no carefully designed clinical trials
      to inform clinicians how to definitely manage athletes with occult CVD. We
      provide a narrative review of the risks and benefits of exercise in active
      individuals with CVD, and our approach to evaluating and managing these risks.

PMID- 28502847
TI  - The Role for Cardiologists in Stroke Intervention.
AB  - Even though cardiovascular disease (CVD) is still the leading cause of death in
      the United States, stroke is the second leading global cause of death behind CVD.
      In the 21st Century, less than 40% of overall stroke patients are discharged to
      home and almost 25% of Medicare beneficiaries do not survive 90 days. In spite of
      the fact that tissue plasminogen activator (TPA) has been approved for stroke
      care for 20 years, only .75% of annual strokes are actually treated with
      intravenous (IV) TPA. Similar to how interventional cardiologists evolved from IV
      to catheter mechanical treatment for acute myocardial infarctions (AMI) over 30
      years ago, over the last few years, neurointerventionists now perform
      endovascular stroke therapy in many of these patients using stent retrievers.
      However, very few stroke patients are actually getting treatment, and
      neurointerventionists on an average perform only 8 stroke interventions per year.
      It has been recently shown that 9 out of 10 strokes can be prevented by
      controlling CVD risk factors. A principal job for cardiologists is to recognize
      and manage these CVD risk factors in addition to being involved with performing
      intervention. Atrial Fibrillation is certainly a common problem in all of our
      practices and puts people at five-fold higher risk of stroke. Cardiovascular
      cardiology teams already have 24/7 coverage for acute interventions for AMI in
      place at their facilities. A number of groups have replicated acute stroke care
      performed by cardiologists at centers worldwide with outstanding results. It
      makes sense that we try to build a collaboration among neuroradiologists,
      interventional cardiologists and perhaps vascular or neurosurgeons with expertise
      in acute endovascular procedures to develop programs for acute and active 24/7
      stroke care similar to systems for primary angioplasty for AMI.

PMID- 28502845
TI  - Foundations of layer-specific fMRI and investigations of neurophysiological
      activity in the laminarized neocortex and olfactory bulb of animal models.
AB  - Laminar organization of neuronal circuits is a recurring feature of how the brain
      processes information. For instance, different layers compartmentalize different
      cell types, synaptic activities, and have unique intrinsic and extrinsic
      connections that serve as units for specialized signal processing. Functional MRI
      is an invaluable tool to investigate laminar processing in the in vivo human
      brain, but it measures neuronal activity indirectly by way of the hemodynamic
      response. Therefore, the accuracy of high-resolution laminar fMRI depends on how
      precisely it can measure localized microvascular changes nearest to the site of
      evoked activity. To determine the specificity of fMRI responses to the true
      neurophysiological responses across layers, the flexibility to invasive
      procedures in animal models has been necessary. In this review, we will examine
      different fMRI contrasts and their appropriate uses for layer-specific fMRI, and
      how localized laminar processing was examined in the neocortex and olfactory
      bulb. Through collective efforts, it was determined that microvessels, including
      capillaries, are regulated within single layers and that several endogenous and
      contrast-enhanced fMRI contrast mechanisms can separate these neural-specific
      vascular changes from the nonspecific, especially cerebral blood volume-weighted
      fMRI with intravenous contrast agent injection. We will also propose some open
      questions that are relevant for the successful implementation of layer-specific
      fMRI and its potential future directions to study laminar processing when
      combined with optogenetics.

PMID- 28502849
TI  - The Interaction of Cardiorespiratory Fitness With Obesity and the Obesity Paradox
      in Cardiovascular Disease.
AB  - Overweight and obesity are well-established risk factors for most cardiovascular
      diseases (CVD), including coronary heart disease (CHD), heart failure (HF), and
      atrial fibrillation. Despite the strong link between excess adiposity and risk of
      CVD, growing evidence has demonstrated an obesity paradox in patients with CVD.
      This phenomenon is characterized by a better prognosis in overweight and mildly
      obese CVD patients than their leaner counterparts. Moreover, the worst outcomes
      are often incurred by underweight CVD patients, followed by those of normal
      weight or severely obese. The obesity paradox is now a well-established
      phenomenon across different types of CVD, and it occurs regardless of age and
      ethnicity of patients, and severity of CVD. Physical inactivity and low
      cardiorespiratory fitness (CRF) have long been recognized as major risk factors
      for CVD. In contrast, high levels of physical activity (PA) and CRF largely
      neutralize the adverse effects of excess adiposity and other traditional CVD risk
      factors, including hypertension, metabolic syndrome, and type-2 diabetes. Higher
      CRF also results in better CVD outcomes across different BMI groups and
      significantly alters the obesity paradox in patients with HF and CHD. Prognostic
      benefits of overweight/obesity tend to be limited to unfit patients with HF and
      CHD, and the obesity paradox usually disappears with improved levels of CRF.
      Nevertheless, increased PA and exercise training, to maintain or improve CRF, are
      effective, safe, and proven strategies for primary and secondary prevention of
      CVD in all weight groups. In this review, we discuss the current concepts of
      individual and combined contributions of fatness and fitness to CVD risk and
      prognosis. We then examine the influence of fitness on the obesity paradox in
      individuals with CVD.

PMID- 28502850
TI  - Cost-Effectiveness of a Bronchial Genomic Classifier for the Diagnostic
      Evaluation of Lung Cancer.
AB  - INTRODUCTION: The use of a bronchial genomic classifier has been shown to improve
      the diagnostic accuracy of bronchoscopy for suspected lung cancer by identifying
      patients who may be more suitable for radiographic surveillance as opposed to
      invasive procedures. Our objective was to assess the cost-effectiveness of
      bronchoscopy plus a genomic classifier versus bronchoscopy alone in the
      diagnostic work-up of patients at intermediate risk for lung cancer. METHODS: A
      decision-analytic Markov model was developed to project the costs and effects of
      two competing strategies by using test performance from the Airway Epithelial
      Gene Expression in the Diagnosis of Lung Cancer-1 and Airway Epithelial Gene
      Expression in the Diagnosis of Lung Cancer-2 studies. The diagnostic accuracy of
      noninvasive and invasive follow-up, as well as associated adverse event rates,
      were derived from published literature. Procedure costs were based on claims data
      and 2016 inpatient and outpatient reimbursement amounts. The model projected the
      number of invasive follow-up procedures, 2-year costs and quality-adjusted life
      years (QALYs) by strategy, and resulting incremental cost-effectiveness ratio
      discounted at 3% per annum. RESULTS: Use of the genomic classifier reduced
      invasive procedures by 28% at 1 month and 18% at 2 years, respectively. Total
      costs and QALY gain were similar with classifier use ($27,221 versus $27,183 and
      1.512 versus 1.509, respectively), resulting in an incremental cost-effectiveness
      ratio of $15,052 per QALY. CONCLUSIONS: Our analysis suggests that the use of a
      genomic classifier is associated with meaningful reductions in invasive
      procedures at about equal costs and is therefore a high-value strategy in the
      diagnostic work-up of patients at intermediate risk of lung cancer.

PMID- 28502851
TI  - Inhibitory effect of alliin from Allium sativum on the glycation of superoxide
      dismutase.
AB  - Inhibition of glycation is an important approach for alleviating diabetic
      complications. Alliin, the most abundant sulphur compound in garlic has been
      demonstrated to possess antidiabetic activity. However, there is no scientific
      evidence supporting its antiglycating activity. The objective of this study was
      to determine the inhibitory effect of alliin on glucose and methyglyoxal (MG)
      induced glycation of an important antioxidant enzyme, superoxide dismutase (SOD).
      Glycation of SOD resulted in a decrease in enzyme activity, fragmentation/cross
      linking, reduced cross-reactivity with anti-SOD antibodies, both tertiary and
      secondary structural changes, and formation of AGEs and fibrils. Alliin offered
      protection against glucose or MG induced glycation of SOD. The antiglycating
      potential of alliin appears to be comparable with that of quercetin which is
      reported to be a potent natural inhibitor of glycation. Alliin has a good
      antiglycating effect and hence is expected to have therapeutic potential in the
      prevention of glycation-mediated diabetic complications.

PMID- 28502852
TI  - Effect of modification with 1,4-alpha-glucan branching enzyme on the rheological
      properties of cassava starch.
AB  - Steady and dynamic shear measurements were used to investigate the rheological
      properties of cassava starches modified using the 1,4-alpha-glucan branching
      enzyme (GBE) from Geobacillus thermoglucosidans STB02. GBE treatment lowered the
      hysteresis loop areas, the activation energy (Ea) values and the parameters in
      rheological models of cassava starch pastes. Moreover, GBE treatment increased
      its storage (G') and loss (G") moduli, and decreased their tan delta (ratio of
      G"/G') values and frequency-dependencies. Scanning electron microscopic studies
      showed the selective and particular attack of GBE on starch granules, and X-ray
      diffraction analyses showed that GBE treatment produces significant structural
      changes in amylose and amylopectin. These changes demonstrate that GBE
      modification produces cassava starch with a more structured network and improved
      stability towards mechanical processing. Differential scanning calorimetric
      analysis and temperature sweeps indicated greater resistance to granule rupture,
      higher gel rigidity, and a large decrease in the rate of initial conformational
      ordering with increasing GBE treatment time. Pronounced changes in rheological
      parameters revealed that GBE modification enhances the stability of cassava
      starch and its applicability in the food processing industry.

PMID- 28502854
TI  - Characterization of a bi-functional cellulase produced by a gut bacterial
      resident of Rosaceae branch borer beetle, Osphranteria coerulescens (Coleoptera:
      Cerambycidae).
AB  - A cellulolytic bacterium was obtained from the digestive tract of Osphranteria
      coerulescens. The breakdown of woody and cellulosic substances by this insect may
      be relative in part to its symbiont bacteria. Under optimal cultural conditions
      the novel isolate produced 5.35U/ml cellulase after 72h. The enzyme was purified
      to 36 fold with a 0.59% yield and showed a specific activity of 9.0U/mg. It
      presented its maximum activity at 60 degrees C and pH 5, while it was stable in a
      wide range of temperature from 20 to 60 degrees C and pH from 5 to 10. The
      purified enzyme had a molecular weight of 42.50kDa based on SDS-PAGE and zymogram
      analyses. It demonstrated high ions and solvent stability and its activity was
      stimulated by Mn2+, Na+, DMSO and chloroform. The enzyme could hydrolyze CMC,
      avicel, cellulose and sawdust. TLC analysis represented the cellobiose as the
      hydrolytic product of CMC. With regard to endo/exo glucanase activity and wide
      pH, temperature and solvent stability, it has potential for industrial
      application.

PMID- 28502853
TI  - Cloning, characterization, and function of MyD88 in silvery pomfret (Pampus
      argenteus) in response to bacterial challenge.
AB  - Myeloid differentiation factor 88 (MyD88) is a key and universal downstream
      adapter for most Toll-like receptors (TLRs) and plays an important role in both
      the innate and adaptive immune response. In this study, the full-length cDNA of
      MyD88 (PAMyD88) from silvery pomfret (Pampus argenteus) was cloned and
      characterized. The PAMyD88 cDNA is 1545bp in length and contains an 876bp open
      reading frames (ORF). Multiple sequence alignment and phylogenetic tree analyzes
      revealed that the amino acid sequence of PAMyd88 was homologous to a variety of
      previously MyD88 molecules characterized from other species. The quantitative
      real-time reverse transcription-PCR analysis showed that the PAMyD88 mRNA was
      broadly expressed in all examined tissues, with higher levels observed in the
      immune-relevant organs. The results showed a significant up-regulation of the
      TLR2 and PAMyD88 transcript levels in response to L. plantarum and C. butyricum
      and a substantial expression level of TLR4 and PAMyD88 induced by V. anguillarum.
      Additionally, a challenge with V. anguillarum resulted in significant apoptosis,
      whereas the L. plantarum and C. butyricum induced only low levels of apoptosis.
      These data provide insight into the roles of PAMyD88 in the TLR signaling pathway
      in response to probiotic and pathogenic bacteria in silvery pomfrets.

PMID- 28502855
TI  - Caesalpinia bonduc serine proteinase inhibitor CbTI-2: Exploring the
      conformational features and antimalarial activity.
AB  - Seeds of tropical legumes posses a repertoire of proteinase inhibitors (PI) and
      the current study highlights some structural/functional features of a strong
      serine PI from the seeds of Caesalpinia bonduc (CbTI-2). Following purification,
      N-terminal sequence of CbTI-2 revealed over 40% similarity with a few serine PIs
      of Caesalpinioideae subfamily. Upon exposure to metal ions and ionic/non ionic
      surfactants, CbTI-2 showed immense variation in the levels of antitryptic
      activity. Exposure of CbTI-2 to 1,4-Dithiothreitol, Guanidinium HCl, H2O2 and
      Dimethyl sulfoxide led to a steady loss of inhibitory activity. Chemical
      modification of amino acids suggested an arginine as the active site residue.
      Circular Dichroism spectrum of native CbTI-2 revealed an unordered state.
      Secondary structure composition of CbTI-2 following exposure to extreme
      conditions (heat, acidic/alkaline environment, Guanidine hydrochloride and DTT)
      showed considerable perturbations that caused severe loss of antiproteolytic
      activity. DLS studies yielded a hydrodynamic radius of ~2.2nm for CbTI-2 and also
      reconfirmed 1:1 stoichiometry for the trypsin-CbTI-2 complex. Initial studies
      indicated CbTI-2 to be a potent antiplasmodial agent by being highly toxic
      towards growth, schizont rupture process and erythrocytic invasion of Plasmodium
      falciparum.

PMID- 28502856
TI  - DNA chip based sensor for amperometric detection of infectious pathogens.
AB  - Several infectious pathogens are found in human whose detection is essential for
      rapid cure of diseases. The most commonly found pathogen in human is
      Streptococcus pyogenes which leads to a wide range of infections from mild
      pharyngitis to rheumatic heart disease. An ultrasensitive DNA chip based sensor
      was developed for quick identification of pathogen S. pyogenes from patient
      throat swab samples. The amperometric response was measured after hybridization
      of specific probe with single stranded genomic DNA (ssG-DNA) from the patient
      samples. The DNA chip was characterized by FTIR, SEM and validated with suspected
      patient real samples. The sensitivity of the DNA chip based sensor was found
      951.34(MUA/cm2)/ng DNA and lower limit of detection (LOD) was 130fg/6MUL samples.
      The DNA chip based sensor is highly specific and takes only 30min for
      identification of specific pathogen.

PMID- 28502857
TI  - Spirostanol saponins from Ypsilandra parviflora induce platelet aggregation.
AB  - Phytochemical investigation on the whole plants of Ypsilandra parviflora led to
      the isolation of seven new spirostanol saponins, named ypsiparosides A-G,
      together with 14 known saponins. Their structures were unambiguously established
      based on extensive spectroscopic evidence and chemical methods. The induced
      rabbit platelet aggregation activities of the isolates were tested. Compounds 4,
      15, and 17 showed maximal platelet aggregation rates ranging from 43 to 55% at a
      concentration of 300MUg/mL. Further experiments exhibited that compounds 4, 15,
      and 17 possessed EC50 values of 642.9, 95.3, and 300.8MUg/mL, respectively.

PMID- 28502858
TI  - Absolute quantification of cholesteryl esters using liquid chromatography-tandem
      mass spectrometry uncovers novel diagnostic potential of urinary sediment.
AB  - BACKGROUND: Urine has been utilized as a source of biomarkers in renal disease.
      However, urinary lipids have not attracted much attention so far. Here we studied
      urinary cholesteryl ester (CE) and its relevance in renal disease. METHODS:
      Quantitative analysis of CE molecular species in serum, urinary supernatant, and
      urinary sediment from patients with renal disease (N=64) and non-renal disease
      (N=23) was carried out using liquid chromatography-tandem mass spectrometry (LC
      MS/MS) and deuterated CEs as internal standards. RESULTS: Validation study showed
      good precision and accuracy of LC-MS/MS. Many CE species were detected in the
      urinary sediment and supernatant in the renal disease group, whereas only a few
      CE species were detected in the other group. In the renal disease group, the sum
      of the concentrations of all CE species showed a significant correlation between
      the sediment and the supernatant from urinary samples (r=0.876, p<0.001);
      however, the composition of CEs was significantly different between them.
      Further, the composition of CEs of the supernatant was similar to that of the
      serum. CONCLUSIONS: Our LC-MS/MS analysis uncovered a distinct CE profile in
      urinary sediment from patients with renal disease, suggesting a possible
      contribution of CEs in urothelial cells to the development of renal disease.

PMID- 28502860
TI  - Structure-activity relationship of brassinosteroids and their agricultural
      practical usages.
AB  - Brassinosteroids (BRs) control several important agronomic traits, such as
      strengthening resistance to diverse adversity, improving the quality, and
      increasing crop yield. Their chemical structures and varieties, specific methods
      for the evaluation of bioactivities, structure-activity relationships, potential
      novel compounds, and practical agricultural uses were summarized. The findings
      allow the examination of brassinosteroids in two important issues: 1) Do the
      results of different bioevaluation protocols provide similar activities for BRs?
      and 2) which bioevaluated compounds would proof to have a greater potential for
      application in agricultural usages?

PMID- 28502859
TI  - The significance of estradiol metabolites in human corpus luteum physiology.
AB  - The human corpus luteum (CL) is a temporary endocrine gland derived from the
      ovulated follicle. Its formation and limited lifespan is critical for steroid
      hormone production required to support menstrual cyclicity, endometrial
      receptivity for successful implantation, and the maintenance of early pregnancy.
      Endocrine and paracrine-autocrine molecular mechanisms associated with
      progesterone production throughout the luteal phase are critical for the
      development, maintenance, regression, and rescue by hCG which sustains CL
      function into early pregnancy. However, the signaling systems driving the
      regression of the primate corpus luteum in non-conception cycles are not well
      understood. Recently, there has been interest in the functional roles of
      estradiol metabolites (EMs), mostly in estrogen-producing tissues. The human CL
      produces a number of EMs, and it has been postulated that the EMs acting via
      paracrine-autocrine pathways affect angiogenesis or LH-mediated events. The
      present review describes advances in understanding the role of EMs in the
      functional lifespan and regression of the human CL in non-conception cycles.

PMID- 28502861
TI  - Analysis of testosterone fatty acid esters in the digestive gland of mussels by
      liquid chromatography-high resolution mass spectrometry.
AB  - Several studies have indicated that up to 70% of the total steroids detected in
      molluscs are in the esterified form and that pollutants, by modifying the
      esterification of steroids with fatty acids, might act as endocrine disrupters.
      However, despite the strong physiological significance of this process, there is
      almost no information on which fatty acids form the steroid esters and how this
      process is modulated. This study (a) investigates the formation of fatty acid
      esters of testosterone in digestive gland microsomal fractions of the mussel
      Mytilus galloprovincialis incubated with either palmitoly-CoA or CoA and ATP, and
      (b) assesses whether the endocrine disruptor tributyltin (TBT) interferes with
      the esterification of testosterone. Analysis of testosterone esters was performed
      by liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). When
      microsomal fractions were incubated with testosterone and palmitoly-CoA, the
      formation of testosterone palmitate was detected. However, when microsomes were
      incubated with CoA and ATP, and no exogenous activated fatty acid was added, the
      synthesis of 16:0, 16:1, 20:5 and 22:6 testosterone esters was observed. The
      presence of 100uM TBT in the incubation mixture did not significantly alter the
      esterification of testosterone. These results evidence the conjugation of
      testosterone with the most abundant fatty acids in the digestive gland microsomal
      fraction of mussels.

PMID- 28502862
TI  - 11 beta-hydroxysteroid dehydrogenase 2 promoter methylation is associated with
      placental protein expression in small for gestational age newborns.
AB  - Small for gestational age infants have greater risk of developing metabolic
      diseases in adult life. It has been suggested that low birth weight may result
      from glucocorticoid excess in utero, a key mechanism in fetal programming. The
      placental enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11beta-HSD2,
      HSD11B2 gene) acts as a barrier protecting the fetus from maternal corticosteroid
      deleterious effects. Low placental 11beta-HSD2 transcription and activity have
      been associated with low birth weight, yet the mechanism regulating its protein
      expression is not fully understood. In the present study we aimed to analyze
      11beta-HSD2 protein expression in placentas of adequate and small for gestational
      age (AGA and SGA, respectively) newborns from healthy mothers, and to explore
      whether 11beta-HSD2 protein expression could be modulated by DNA methylation.
      11beta-HSD2 protein levels were measured by western blot in placental biopsies
      from term AGA and SGA infants (n=10 per group). DNA methylation was profiled both
      globally and in the HSD11B2 promoter by liquid chromatography with UV detection
      and methylation-specific melting curve analysis, respectively. We found lower
      placental 11beta-HSD2 protein expression and higher HSD11B2 promoter methylation
      in SGA compared to AGA. Promoter methylation was inversely correlated with both
      protein expression and, importantly, birth weight. No changes in global placental
      methylation were found. In conclusion, lower 11beta-HSD2 protein expression is
      associated with higher HSD11B2 promoter methylation, correlating with birth
      weight in healthy pregnancy. Our data support the role of 11beta-HSD2 in
      determining birth weight, providing evidence of its regulation by epigenetic
      mechanisms, which may affect postnatal metabolic disease risk.

PMID- 28502863
TI  - Synthesis of 16alpha-amino-pregnenolone derivatives via ionic liquid-catalyzed
      aza-Michael addition and their evaluation as C17,20-lyase inhibitors.
AB  - Aza-Michael addition of 16-dehydropregnenolone was studied in the presence of a
      basic ionic liquid, [DBU][OAc] as catalyst and solvent. The reaction was carried
      out using different primary and secondary amines as N-nucleophiles. The products
      were obtained in moderate to good yields and were characterized by 1H and 13C
      NMR, MS and IR. The ionic liquid was found to be an efficient and recyclable
      catalyst that was reused five times. The products were investigated for the
      inhibition of in vitro C17,20-lyase activity and displayed moderate inhibitory
      effect.

PMID- 28502864
TI  - Chagas disease in Europe: A review for the internist in the globalized world.
AB  - Chagas disease (CD) or American trypanosomiasis identified in 1909 by Carlos
      Chagas, has become over the last 40years a global health concern due to the huge
      migration flows from Latin America to Europe, United States, Canada and Japan. In
      Europe, most migrants from CD-endemic areas are concentrated in Spain, Italy,
      France, United Kingdom and Switzerland. Pooled seroprevalence studies conducted
      in Europe show an overall 4.2% prevalence, with the highest infection rates
      observed among individuals from Bolivia (18.1%). However, in most European
      countries the disease is neglected with absence of screening programmes and low
      access to diagnosis and treatment. Physicians working in Europe should also be
      aware of the risk of autochthonous transmission of Trypanosoma cruzi to newborns
      by their infected mothers and to recipients of blood or transplanted organs from
      infected donors. Finally, physicians should be able to recognize and treat the
      most frequent and serious complications of chronic Chagas disease, namely
      cardiomyopathy, megacolon and megaesophagus. This review aims to highlights the
      problem of CD in Europe by reviewing papers published by European researchers on
      this argument, in order to raise the awareness of internists who are bound to
      increasingly encounter patients with the disease in their routine daily
      activities.

PMID- 28502865
TI  - Cartilage oligomeric matrix protein on the spot for liver fibrosis evaluation:
      Too early or too late?

PMID- 28502866
TI  - What is inappropriate hospital use for elderly people near the end of life? A
      systematic review.
AB  - BACKGROUND: Older people with advance chronic illness use hospital services
      repeatedly near the end of life. Some of these hospitalizations are considered
      inappropriate. AIM: To investigate extent and causes of inappropriate hospital
      admission among older patients near the end of life. METHODS: English language
      publications in Medline, EMBASE, PubMed, Cochrane library, and the grey
      literature (January 1995-December 2016) covering community and nursing home
      residents aged >=60years admitted to hospital. OUTCOMES: measurements of
      inappropriateness. A 17-item quality score was estimated independently by two
      authors. RESULTS: The definition of 'Inappropriate admissions' near the end of
      life incorporated system factors, social and family factors. The prevalence of
      inappropriate admissions ranged widely depending largely on non-clinical reasons:
      poor availability of alternative sites of care or failure of preventive actions
      by other healthcare providers (1.7-67.0%); family requests (up to 10.5%); or too
      late an admission to be of benefit (1.7-35.0%). The widespread use of subjective
      parameters not routinely collected in practice, and the inclusion of non-clinical
      factors precluded the true estimation of clinical inappropriateness. CONCLUSIONS:
      Clinical inappropriateness and system factors that preclude alternative community
      care must be measured separately. They are two very different justifications for
      hospital admissions, requiring different solutions. Society has a duty to ensure
      availability of community alternatives for the management of ambulatory-sensitive
      conditions and facilitate skilling of staff to manage the terminally ill in non
      acute settings. Only then would the evaluation of local variations in clinically
      inappropriate admissions and inappropriate length of stay be possible to
      undertake.

PMID- 28502867
TI  - Screening for occult cancer in idiopathic venous thromboembolism - Systemic
      review and meta-analysis.
AB  - BACKGROUND: Idiopathic venous thromboembolism (VTE) may be associated with an
      occult malignancy. Early detection of cancer might be translated to a better
      prognosis for these patients. However, the efficacy of extensive screening for
      cancer in patients with idiopathic VTE is controversial. MATERIALS AND METHODS:
      Systemic review and meta-analysis of all available prospective trials comparing
      extensive to limited screening for occult malignancies in patients with
      idiopathic VTE. PRIMARY OUTCOME: all-cause mortality. SECONDARY OUTCOMES: cancer
      related mortality, early cancer diagnosis, cancer diagnosis at the end of follow
      up and cancer diagnosis at an early stage. Risk ratios (RR) with 95% confidence
      intervals (CIs) were estimated and pooled. RESULTS: The study included five
      trials and 2287 patients. Extensive screening did not affect all-cause mortality
      at the end of follow up [RR 0.86 (95% CI 0.58-1.27)] or cancer-related mortality
      [RR 0.93 (95% CI 0.54-1.58)]. Yet, it yielded more diagnoses of cancer [RR 2.17
      (95% CI 1.42-3.32)]. Rates of cancer diagnosis at an early stage did not differ
      statistically between the two groups [RR 1.49 (95% CI 0.86-2.56)]. However,
      analysis of the randomized controlled trials alone showed a tendency towards
      early stage cancer at diagnosis in extensive screening group in, with results
      almost statistically significant [RR 2.14 (95% CI 0.98-4.67), p=0.06].
      CONCLUSIONS: Extensive screening for malignancy after idiopathic VTE does not
      affect mortality rates. Yet, it yields more cancer diagnoses shortly after the
      VTE event. Further research is needed to determine whether extensive screening
      might be proper for specific high risk populations.

PMID- 28502868
TI  - No pain, no gain: Male plasticity in burrow digging according to female rejection
      in a sand-dwelling wolf spider.
AB  - Behavioral plasticity allows individuals to reversibly respond to short-term
      variations in their ecological and social environment in order to maximize their
      fitness. Allocosa senex is a burrow-digging spider that inhabits the sandy coasts
      of South America. This species shows a reversal in typical sex roles expected in
      spiders: females are wanderers that visit males at their burrows and initiate
      courtship. They prefer males with long burrows for mating, and males prefer
      virgin over mated females. We tested whether female sexual rejection induced
      males to enlarge their burrows and if female reproductive status affected males'
      responses. We exposed males who had constructed burrows to: a) virgin females or
      b) mated females, (n=16 for each category). If female rejection occurred, we
      repeated the trial 48h later with the same female. As control, we maintained a
      group of males without female exposure (unexposed group, n=32). Rejected males
      enlarged their burrows more frequently and burrows were longer compared to
      unexposed males. However, frequency and length of enlargement did not differ
      according to female reproductive status. Males of A. senex showed plasticity in
      digging behavior in response to the availability of females, as a way to maximize
      the possibilities of future mating.

PMID- 28502869
TI  - Comparative analysis of osteoblast gene expression profiles and Runx2 genomic
      occupancy of mouse and human osteoblasts in vitro.
AB  - Fast progress of the next generation sequencing (NGS) technology has allowed
      global transcriptional profiling and genome-wide mapping of transcription factor
      binding sites in various cellular contexts. However, limited number of replicates
      and high amount of data processing may weaken the significance of the findings.
      Comparative analyses of independent data sets acquired in the different
      laboratories would greatly increase the validity of the data. Runx2 is the key
      transcription factor regulating osteoblast differentiation and bone formation. We
      performed a comparative analysis of three published Runx2 data sets of chromatin
      immunoprecipitation followed by deep sequencing (ChIP-seq) analysis in
      osteoblasts from mouse and human origin. Moreover, we assessed the similarity of
      the corresponding transcription data of these studies available online. The ChIP
      seq data analysis confirmed general features of Runx2 binding, including location
      at genic vs intergenic regions and abundant Runx2 binding on promoters of the
      highly expressed genes. We also found high frequency of Runx2 DNA binding without
      a consensus Runx2 motif at the binding site. Importantly, mouse and human Runx2
      showed moderately similar binding patterns in terms of peak-associated closest
      genes and their associated genomic ontology (GO) pathways. Accordingly, the gene
      expression profiles were highly similar and osteoblastic phenotype was prominent
      in the differentiated stage in both species. In conclusion, ChIP-seq method shows
      good reproducibility in the context of mature osteoblasts, and mouse and human
      osteoblast models resemble each other closely in Runx2 binding and in gene
      expression profiles, supporting the use of these models as adequate tools in
      studying osteoblast differentiation.

PMID- 28502870
TI  - Comparison of longevity and clinical outcomes of implantable cardioverter
      defibrillator leads among manufacturers.
AB  - BACKGROUND: An early failure of the Biotronik Linox S/SD implantable cardioverter
      defibrillator (ICD) lead has been reported. We have also experienced several
      cases with early failure of Linox leads. OBJECTIVE: Our aim was to assess the
      longevity of Linox S/SD (Biotronik, Berlin, Germany) compared with Sprint Fidelis
      (Medtronic, Minneapolis, MN), Sprint Quattro (Medtronic), and Endotak Reliance
      (Boston Scientific, Natick, Massachusetts) leads. METHODS: We retrospectively
      reviewed patients who had undergone implantation of Linox S/SD (n = 90), Sprint
      Fidelis (n = 37), Sprint Quattro (n = 27), or Endotak Reliance (n = 50) leads
      between June 2000 and December 2013 at our hospital. Variables associated with
      lead failure were assessed by the Kaplan-Meier method and Cox survival modeling.
      RESULTS: Failure rates of Linox, Sprint Fidelis, and Endotak leads were 3.2%/year
      (7-year survival rate, 81.0%), 3.4%/year (7-year survival rate, 77.2%), and
      0.61%/year (7-year survival rate, 95.8%), respectively. No lead failure was found
      with Sprint Quattro leads. The survival probability of Linox leads was
      significantly lower than that of Endotak leads (P = .049) and comparable to that
      of Sprint Fidelis leads (P = .69). In univariate analysis, age was the only
      predictor of Linox lead failure. Patients <58 years old were at significantly
      increased risk of lead failure compared with patients >=58 years old (hazard
      ratio, 9.0; 95% confidence interval, 1.13-71.3; P = .037). CONCLUSION: In our
      single-center experience, the survival rate of Linox leads was unacceptably low.
      The only predictor of Linox lead failure was age at implantation. This is the
      first description of a lower survival rate for Linox leads in an Asian
      population.

PMID- 28502871
TI  - A leadless pacemaker in the real-world setting: The Micra Transcatheter Pacing
      System Post-Approval Registry.
AB  - BACKGROUND: First-in-man studies of leadless pacemakers have demonstrated high
      rates of implant success, and safety and efficacy objectives were achieved.
      Outside of the investigational setting, there are concerns, particularly over
      cardiac effusion and perforation, device dislodgement, infection, telemetry, and
      battery issues. OBJECTIVE: The acute performance of the Micra transcatheter
      pacemaker from a worldwide Post-Approval Registry is reported. METHODS: The
      registry is an ongoing prospective single-arm observational study designed to
      assess the safety and effectiveness of Micra in the post-approval setting. The
      safety end point was system- or procedure-related major complications at 30 days
      post implant. We compared the major complication rate with that of the 726
      patients from the investigational study. Electrical performance was also
      characterized. RESULTS: The device was successfully implanted in 792 of 795
      registry patients (99.6%) by 149 implanters at 96 centers in 20 countries.
      Through 30 days post implant, a total of 13 major complications occurred in 12
      patients, for a major complication rate of 1.51% (95% confidence interval, 0.78%
      2.62%). Major complications included cardiac effusion/perforation (1, 0.13%),
      device dislodgement (1, 0.13%), and sepsis (1, 0.13%). After adjusting for
      baseline differences, the rate of major complications in the registry trended
      lower than the investigational trial (odds ratio, 0.58, 95% confidence interval,
      0.27-1.25; P = .16). Early pacing capture thresholds were low and stable.
      CONCLUSION: Performance of the Micra transcatheter pacemaker in a real-world
      setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%)
      of major complications through 30 days post implant. In particular, the rates of
      pericardial effusion, device dislodgement, and infection were low, reinforcing
      the positive results seen in the investigational study.

PMID- 28502872
TI  - Subcutaneous implantable cardioverter-defibrillator Post-Approval Study: Clinical
      characteristics and perioperative results.
AB  - BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was
      developed to reduce short- and long-term complications associated with
      transvenous ICD leads. Early multicenter studies included younger patients with
      less left ventricular systolic dysfunction and fewer comorbidities than cohorts
      with traditional ICD. OBJECTIVE: The purpose of this study was to characterize
      patient selection and the acute performance of the S-ICD in a contemporary real
      world setting. METHODS: The S-ICD Post-Approval Study is a prospective registry
      involving 86 US centers. Patients were enrolled if they met criteria for S-ICD
      implantation, passed an electrocardiogram screening test, and had a life
      expectancy of >1 year. Analyses of descriptive statistics, Kaplan-Meier time to
      event, and multivariate logistic regression were performed. RESULTS: The study
      includes 1637 patients who underwent S-ICD implantation. The cohort included
      68.6% (1123/1637) male patients, and 13.4% (220/1636) were receiving dialysis for
      end-stage renal disease. The mean age was 52 +/- 15 years, with a mean left
      ventricular ejection fraction of 32.0% +/- 14.6%. Electrocardiogram screening was
      successful for at least 1, 2, or 3 vectors in 100%, 93.8%, and 51.4% of patients,
      respectively. Medical imaging (65.1%, 1065/1636) and general anesthesia (64.1%,
      1048/16) were used in a majority of patients, and 52.2% (855/1637) were implanted
      with the 2-incision technique. Induced ventricular tachycardia/ventricular
      tachycardia was successfully converted in 98.7% (1394/1412) of patients. The 30
      day complication-free rate was 96.2%. Predictors of complications included
      diabetes, younger age, and higher body mass index. CONCLUSION: Contemporary US
      patients with S-ICD have more comorbidities than do previous cohorts with S-ICD,
      but they are younger with more end-stage renal disease than do patients with
      transvenous ICD. Implantation success is high, and short-term complication rates
      are acceptable.

PMID- 28502874
TI  - Aerobic vaginitis: no longer a stranger.
AB  - Aerobic vaginitis (AV) is the name given in 2002 to a vaginal infectious entity
      which was not recognized as such before. It is characterized by abnormal
      (dysbiotic) vaginal microflora containing aerobic, enteric bacteria, variable
      levels of vaginal inflammation and deficient epithelial maturation. Although AV
      and bacterial vaginosis (BV) share some characteristics, such as a diminished
      number or absence of lactobacilli, increased discharge (fishy smelling in BV,
      while in severe forms of AV, a foul, rather rotten smell may be present) and
      increased pH (often more pronounced in AV), there are also striking differences
      between the two. There is no inflammation in women with BV, whereas the vagina of
      women with AV often appears red and edematous, and may even display small
      erosions or ulcerations. The color of the discharge in BV is usually whitish or
      gray and of a watery consistency, whereas in AV it is yellow to green and rather
      thick and mucoid. Women with BV do not have dyspareunia, while some women with
      severe AV do. Finally, the microscopic appearance differs in various aspects,
      such as the presence of leucocytes and parabasal or immature epithelial cells in
      AV and the absence of the granular aspect of the microflora, typical of BV.
      Despite all these differences, the distinction between AV and BV was not
      recognized in many former studies, leading to incomplete and imprecise diagnostic
      workouts and erroneous management of patients in both clinical and research
      settings. The prevalence of AV ranges between 7 and 12%, and is therefore less
      prevalent than BV. Although still largely undiagnosed, many researchers and
      clinicians increasingly take it into account as a cause of symptomatic vaginitis.
      AV can co-occur with other entities, such as BV and candidiasis. It can be
      associated with dyspareunia, sexually transmitted infections (such as human
      papilloma virus, human immunodeficiency virus, Trichomonas vaginalis and
      Chlamydia trachomatis), chorioamnionitis, fetal infection, preterm birth and
      cervical dysplasia. Many other possible pathological associations are currently
      under investigation. The diagnosis of AV is made using wet mount microscopy,
      ideally using phase contrast. An AV score is calculated, according to:
      lactobacillary grade, presence of inflammation, proportion of toxic leucocytes,
      characteristics of the microflora and presence of immature epithelial cells. To
      circumvent the hurdle of microscopic investigation, some groups have begun to
      develop nucleic-acid-based and enzymatic diagnostic tests, but the detailed
      information obtained with phase contrast microscopy is irreplaceable. The best
      treatment is not yet fully determined, but it must be tailored according to the
      microscopic findings and the patient's needs. There is a role for local estrogen
      therapy, corticosteroids, antimicrobials and probiotics. Further research will
      reveal more precise data on diagnosis, pathogenesis, management and prevention.

PMID- 28502873
TI  - Synchronization as a mechanism for low-energy anti-fibrillation pacing.
AB  - BACKGROUND: Low-energy anti-fibrillation pacing (LEAP) has been suggested as an
      alternative treatment in symptomatic fibrillation patients. It significantly
      lowers the energy required compared with standard 1-shock defibrillation.
      OBJECTIVE: In this study, we investigated the mechanism of arrhythmia termination
      by LEAP and systematically analyzed the influence of shock period and timing on
      the success rate of LEAP. METHODS: We induced atrial and ventricular fibrillation
      in isolated canine hearts and applied LEAP and standard 1-shock defibrillation to
      terminate the arrhythmia. We simulated the arrhythmia and LEAP using a 2
      dimensional bidomain human atrial model. RESULTS: The ex vivo experiments showed
      successful termination of atrial fibrillation and ventricular fibrillation using
      LEAP, with an average 88% and 81% energy reduction, respectively, and both
      experiments and simulations verified that synchronization from virtual electrodes
      is the key mechanism for termination of arrhythmia by LEAP using modified
      Kuramoto phase plots and fraction of tissue excited (FTE) plots. We also observed
      in simulations that LEAP is more effective when the shock period is close to the
      dominant period and the first shock is delivered when FTE is decreasing.
      CONCLUSIONS: Our results support synchronization as the mechanism for arrhythmia
      termination by LEAP, and its effectiveness can be improved by adjusting shock
      period and timing.

PMID- 28502875
TI  - Efficacy of photodynamic therapy versus antibiotics as an adjunct to scaling and
      root planing in the treatment of periodontitis: A systematic review and meta
      analysis.
AB  - BACKGROUND: To determine whether treatment with antimicrobial photodynamic
      therapy (aPDT) as an adjunct to scaling and root planing (SRP) yield better
      clinical periodontal outcomes than antibiotics (AB) as adjunct to SRP in
      periodontitis. METHODS: Electronic searches were conducted in databases (MEDLINE,
      PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and
      Cochrane Oral Health Group Trials Register databases) up to and including April
      2017. RESULTS: Five randomized trials were included. All studies used the
      combined approach aPDT+SRP and AB+SRP in the test and control group respectively.
      The follow up period ranged from 12 to 48 weeks. All studies used diode lasers.
      The wavelengths, power density and duration of irradiation used were 670
      nanometre, 75 milliwatts per square centimeters and 60s respectively. None of the
      studies showed additional benefits of aPDT at follow up. Considering the effects
      of adjunctive aPDT as compared to AB, a high degree of heterogeneity for
      periodontal probing depth (PPD) (p<0.0001, I2=87.47%) was noticed among both the
      groups. Meta-analysis showed significant clinical attachment level (CAL) gain
      (WMD=0.60, 95% CI=0.25 to 0.95, p=0.001), and not PPD reduction (WMD=0.67, 95%
      CI=-0.36 to 1.71, p=0.204) for aPDT as compared to AB at follow up. CONCLUSION:
      It remains debatable whether aPDT is more effective as compared to adjunctive AB
      in the treatment of periodontitis, given that the scientific evidence is weak.
      Precautions must be exercised when interpreting the results of this study due to
      the small sample size and high heterogeneity among studies.

PMID- 28502876
TI  - Novel strategy in giant cutaneous squamous cell carcinoma treatment: The case
      experience with a combination of photodynamic therapy and surgery.
AB  - The treatment for giant cutaneous squamous cell carcinoma (cSCC) is challenging.
      Here, we reported that a 90-year-old patient with giant cSCC was successfully
      treated through combination of surgery and photodynamic therapy (PDT). Due to the
      advanced patient age, large tumor area, and deep infiltration, radical surgery
      cannot be performed initially. After in situ resection, five rounds of topical 5
      aminolevulinic acid PDT were continuously performed. The surgical wound was
      healed five months after resection. Seven months after initial resection, the
      residual tumor was resected by a radical surgery. The patient was followed up for
      six months after the radical surgical resection and showed no tumor recurrence.
      This case suggested that initial utmost resection for main body of tumor,
      decreasing the tumor boundary by PDT treatment and the sequential treatment
      regimen of radical surgery can be an effective therapeutic schedule for
      refractory and giant cSCC.

PMID- 28502877
TI  - Irradiance dependence of the conduction block of an in vitro cardiomyocyte wire.
AB  - BACKGROUND: To obtain therapeutic condition precisely by in vitro experiment, we
      studied the irradiance dependence of the electrical conduction blockage caused by
      a photodynamic reaction using a high extracellular concentration of talaporfin
      sodium on a novel in vitro cardiomyocyte electrical conduction wire. METHODS: The
      cardiomyocyte wires were constructed on patterned cultivation cover glass, which
      had cultivation areas 60MUm in width, and a maximum length of 10mm. The
      talaporfin sodium concentration was set to 20MUg/mL. The photodynamic reaction
      with a high extracellular photosensitizer concentration was performed with a
      short time interval (approximately 15min) between photosensitizer exposure and
      irradiation. A 663-nm laser was applied to the cardiomyocyte wire, and the
      irradiance was varied between 3 and 120mW/cm2. The cardiomyocyte electrical
      conduction was evaluated using the cross-correlation function of intracellular
      Ca2+ probe fluorescence brightness from an upper and lower section outside the
      laser irradiation area of a wire every 10s, which lasted up to 600s. RESULTS: The
      onset of electrical conduction blockage was defined by an 85% decrease in the
      cross-correlation function, compared with its initial value. The time for the
      electrical conduction blockage decreased from 600 to 300s as the irradiance was
      increased. Also, the probability of electrical conduction blockage was found to
      increase with increasing irradiance. CONCLUSIONS: We found a strong dependence on
      the irradiance for the time and probability of electrical conduction blockage.

PMID- 28502878
TI  - The Relationship Between Sensory Loss and Persistent Pain 1 Year After Breast
      Cancer Surgery.
AB  - : Moderate to severe persistent pain after breast cancer surgery (PPBCS) affects
      10 to 20% of the patients. Sensory dysfunction is often concomitantly present
      suggesting a neuropathic pain state. The relationship between various
      postoperative pain states and sensory dysfunction has been examined using
      quantitative sensory testing (QST), but only 2 smaller studies have examined
      PPBCS and sensory dysfunction in the surgical area. The purpose of this
      prospective study was to assess the relative importance of sensory function and
      PPBCS. QST consisted of sensory mapping, tactile detection threshold, mechanical
      pain threshold, and thermal thresholds. Two hundred ninety patients were enrolled
      and results showed that 38 (13%) had moderate to severe pain and 246 (85%) had
      hypoesthesia in the surgical area 1 year after surgery. Increased hypoesthesia
      areas were associated with pain at rest as well as during movement (P = .0001).
      Pain during movement was associated with a side-to-side difference of 140% (P =
      .001) for tactile detection threshold and 40% (P = .01) for mechanical pain
      threshold as well as increased thermal thresholds in the axilla (P > .001).
      Logistic regression models controlling for confounders showed larger areas of
      hypoesthesia as a significant risk factor, odds ratio 1.85 per 100 cm2 for pain
      at rest and odds ratio 1.36 per 100 cm2 for pain during movement. PERSPECTIVE:
      PPBCS is associated with increasing areas of hypoesthesia as well as
      intraoperative nerve preservation. Thus, we hypothesize that PPBCS is associated
      with an interaction between a peripheral nociceptive drive in macroscopically
      preserved nerves and the central nervous system causing PPBCS as well as
      hypoesthesia. QST may identify patients suitable for intervention.

PMID- 28502879
TI  - Genetic deletion of P-glycoprotein alters stress responsivity and increases
      depression-like behavior, social withdrawal and microglial activation in the
      hippocampus of female mice.
AB  - P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier
      and regulates the brain uptake of various xenobiotics and endogenous mediators
      including glucocorticoid hormones which are critically important to the stress
      response. Moreover, P-gp is expressed on microglia, the brain's immune cells,
      which are activated by stressors and have an emerging role in psychiatric
      disorders. We therefore hypothesised that germline P-gp deletion in mice might
      alter the behavioral and microglial response to stressors. Female P-gp knockout
      mice displayed an unusual, frantic anxiety response to intraperitoneal injection
      stress in the light-dark test. They also tended to display reduced conditioned
      fear responses compared to wild-type (WT) mice in a paradigm where a single
      electric foot-shock stressor was paired to a context. Foot-shock stress reduced
      social interaction and decreased microglia cell density in the amygdala which was
      not varied by P-gp genotype. Independently of stressor exposure, female P-gp
      deficient mice displayed increased depression-like behavior, idiosyncratic
      darting behavior, age-related social withdrawal and hyperactivity, facilitated
      sensorimotor gating and altered startle reactivity. In addition, P-gp deletion
      increased microglia cell density in the CA3 region of the hippocampus, and the
      microglial cells exhibited a reactive, hypo-ramified morphology. Further, female
      P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the
      hippocampus. In conclusion, this research shows that germline P-gp deletion
      affected various behaviors of relevance to psychiatric conditions, and that
      altered microglial cell activity and enhanced GR expression in the hippocampus
      may play a role in mediating these behaviors.

PMID- 28502881
TI  - Multilevel Schwab grade II osteotomies for sagittal plane correction in the
      management of adult spinal deformity.
AB  - BACKGROUND CONTEXT: Prior reports have compared posterior column osteotomies with
      pedicle subtraction osteotomies in terms of utility for correcting fixed sagittal
      imbalance in adolescent patients with deformity. No prior reports have described
      the use of multilevel Smith-Petersen Osteotomies (SPOs) alone for surgical
      correction in the adult spinal deformity (ASD) population. PURPOSE: The study
      aimed to determine the utility of multilevel SPOs in the management of global
      sagittal imbalance in ASD patients. STUDY DESIGN/SETTING: This is a retrospective
      observational study at a single academic center. PATIENT SAMPLE: The sample
      included 85 ASD patients. OUTCOME MEASURES: This is a radiographic outcomes
      cohort study. METHODS: The radiographs of 85 ASD patients were retrospectively
      evaluated before and after long-segment (>5 spinal levels) fusion and multilevel
      SPO (>=3 levels) for sagittal imbalance correction. The number of osteotomies,
      correction in regional lumbar lordosis (LL), and correction per osteotomy was
      evaluated. Independent predictors of correction per SPO were evaluated with a
      hierarchical linear regression analysis. RESULTS: Eighty-five patients (mean age:
      67.5+/-11 years) were identified with ASD (372 SPOs). The mean preoperative
      sagittal vertical axis (SVA) and T1 pelvic angle (TPA) were 8.16+/-6.75 cm and 25
      degrees +/-13.23 degrees , respectively. The mean postoperative central sacral
      vertical line (CSVL) and SVA were 0.67+/-0.70 cm and 1.29+/-5.41 cm,
      respectively. The mean improvement in SVA was 6.29 cm achieved with a correction
      of approximately 5.05 degrees  per SPO. The mean LL restoration was 20.3 degrees
      +/-13.9 degrees , and 33(39%) patients achieved a final pelvic incidence minus
      lumbar lordosis (PI-LL) <=10 degrees . Fifty-four (64%) achieved a postoperative
      PI-LL <=15 degrees , 75 (88%) with a PI-LL <=20 degrees , and 85 (100%) achieved
      a PI-LL <=25 degrees . Correction per SPO was similar regardless of prior fusion
      (4.87 degrees  vs. 5.72 degrees  for revisions, p=.192). In a subgroup analysis
      of SVA greater than 10 cm, there was no significant difference in the final LL,
      thoracic kyphosis, PI-LL, SVA, CSVL, and TPA, as compared with SVA <10 cm. The LL
      was the only independent predictor of osteotomy correction per level (LL: beta
      coefficient=-0.108, confidence interval: -0.141 to 0.071, p<.0001). CONCLUSIONS:
      Multilevel SPOs are feasible for restoration of LL as well as sagittal and
      coronal alignment in the ASD population with or without prior instrumented
      fusion.

PMID- 28502880
TI  - Maternal care modulates the febrile response to lipopolysaccharide through
      differences in glucocorticoid receptor sensitivity in the rat.
AB  - Early life adversity increases the risk for later infection. The febrile response
      is a potent mechanism to combat infection. We found that variations in maternal
      care influence the febrile response to 50ug/kg lipopolysaccharide (LPS) challenge
      in adult male rats. Offspring from low-licking/grooming (LG) mothers had an
      increased febrile response compared to offspring from high-LG mothers challenged
      with LPS. Low-LG offspring had reduced plasma IL-6 at one and two hours post
      challenge compared to high-LG offspring. IL-6 gene expression in the anterior
      hypothalamus was induced following LPS challenge in low-LG offspring but not in
      high-LG offspring at two hours post challenge. Occupancy of the transcription
      factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB)
      to the IL-6 promoter region in the anterior hypothalamus was greater in low-LG
      offspring treated with LPS than in high-LG offspring. These findings suggest
      greater activation of thermoregulatory neurons in the anterior hypothalamus of
      low-LG compared to high-LG offspring following LPS challenge. Low-LG offspring
      had greater plasma corticosterone levels following LPS challenge and they had
      enhanced glucocorticoid receptors (GR) in the spleen compared to high-LG
      offspring. Enhanced glucocorticoids and glucocorticoid receptor sensitivity
      associated with reduced IL-6 induction early post challenge in low-LG offspring.
      Challenge with RU-486 prior to LPS challenge eliminated differences in the
      febrile response between offspring of high and low-LG mothers. Individual
      differences in GR sensitivity may modulate differences in the febrile response to
      LPS challenge, exerting a long-term influence on the capacity to recover from
      infection.

PMID- 28502882
TI  - Single-incision endoscopic thyroidectomy for papillary thyroid cancer: A pilot
      study.
AB  - BACKGROUND: Recently, we have reported single incision endoscopic thyroidectomy
      using an axillary approach with gas inflation (SIET) in cases with benign thyroid
      tumors to reduce post-operative pain and invasiveness of the conventional
      endoscopic thyroidectomy. The aim of this study was to present our experiences
      with SIET for papillary thyroid cancer (PTC). METHODS: Patients who were
      diagnosed with histologically papillary thyroid carcinoma (<=1 cm) with single,
      unilateral, and intra-thyroidal lesion and without clinical lymph node metastasis
      were included. We analyzed clinico-pathological characteristics, surgical
      outcomes, and oncologic adequacy of the SIET procedure. RESULTS: Between January
      2011 and July 2012, a total of 75 patients underwent hemi-thyroidectomy with
      ipsilateral central lymph node dissection via SIET. The mean tumor size was 0.5
      cm and 4.1 +/- 2.43 central lymph nodes were removed. Of the patients, 98.3% were
      satisfied with their surgical wound post-operatively and no critical post
      operative complications occurred during the study, except for one case of post
      operative bleeding. There was one case of disease recurrence, which occurred in
      the contra-lateral cervical lymph node region 6 months after SIET. This patient
      underwent completion thyroidectomy with selective neck dissection. CONCLUSION:
      The SIET is a safe and acceptable procedure for PTC with a reduced dissection
      field, less post-operative pain, and more cosmetic satisfaction than conventional
      endoscopic thyroid surgery.

PMID- 28502883
TI  - Comparative evaluation of colonoscopy-assisted transanal minimally invasive
      surgery via glove port and endoscopic submucosal dissection for early rectal
      tumor.
AB  - BACKGROUND: Early rectal tumor is usually managed by local excision. A novel
      method-colonoscopy-assisted transanal minimally invasive surgery via glove port
      (CA-TAMIS-GP)-for resecting early rectal tumor was developed and compared with
      endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: We performed CA
      TAMIS-GP surgery on 26 patients from January 2014 to February 2016. For better
      analysis, we retrospectively collected data from 31 patients who underwent ESD
      between October 2012 and December 2013; overall, 57 patients diagnosed with early
      rectal tumor were included in this study. Perioperative conditions and long-term
      outcomes of both groups were compared. RESULTS: All lesions were dissected
      completely and successfully without conversion to open surgery or major
      complications. On histopathologic examination, all specimens in this study had
      negative margins. All patients had uneventful postoperative recoveries, except 3
      patients of CA-TAMIS-GP with minor hematochezia, which resolved spontaneously; 7
      ESD patients had late-onset bleeding and 3 needed colonoscopic hemostasis; 2
      patients in each group had mild fever. The CA-TAMIS-GP group had a shorter
      operation time, less hemorrhage, and a lower average consumable cost than the ESD
      group (P < 0.05); moreover, the CA-TAMIS-GP group had no recurrence or long-term
      complications during a follow-up of 10-32 months, whereas3 patients in the ESD
      group developed local recurrence during a follow-up of 24-36 months. CONCLUSIONS:
      The CA-TAMIS-GP is a new method that is safe and effective in patients with early
      rectal tumor and appears to have a shorter operation time and less blood loss as
      compared with ESD.

PMID- 28502884
TI  - Quantifying sex, race, and age specific differences in bone microstructure
      requires measurement of anatomically equivalent regions.
AB  - INTRODUCTION: Individuals differ in forearm length. As microstructure differs
      along the radius, we hypothesized that errors may occur when sexual and racial
      dimorphisms are quantified at a fixed distance from the radio-carpal joint.
      METHODS: Microstructure was quantified ex vivo in 18 cadaveric radii using high
      resolution peripheral quantitative computed tomography and in vivo in 158 Asian
      and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI
      positioned at 4.5-6% of forearm length and using the fixed ROI adjusted for cross
      sectional area (CSA), forearm length or height. Secular effects of age were
      assessed by comparing 38 younger and 33 older women. RESULTS: Ex vivo, similar
      amounts of bone mass fashioned adjacent cross sections. Larger distal cross
      sections had thinner porous cortices of lower matrix mineral density (MMD), a
      larger medullary CSA and higher trabecular density. Smaller proximal cross
      sections had thicker less porous cortices of higher MMD, a small medullary canal
      with little trabecular bone. Taller persons had more distally positioned fixed
      ROIs which moved proximally when corrected. Shorter persons had more proximally
      positioned fixed ROIs which moved distally when corrected, so dimorphisms
      lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity
      and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25
      SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In
      women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than
      Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and
      trabecular density. Results were similar using an adjusted fixed ROI. Adjusting
      for secular effects of age on forearm length resulted in the age-related
      increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). CONCLUSION:
      Assessment of sex, race and age related differences in microstructure requires
      measurement of anatomically equivalent regions.

PMID- 28502885
TI  - Contra-lateral bone loss at the distal radius in postmenopausal women after a
      distal radius fracture: A two-year follow-up HRpQCT study.
AB  - Opposite to the fracture side, bone mineral density (BMD) measured by DXA at the
      contra-lateral side does not change after a distal radius fracture. However, it
      is unknown if also bone micro-architecture and strength at the contralateral side
      are unaffected. Therefore, the aim of this study was to assess BMD, micro
      architecture and bone mechanical properties at the contra-lateral side during two
      years follow-up after a distal radius fracture using high resolution peripheral
      quantitative computed tomography (HRpQCT). The contra-lateral distal radius of 15
      postmenopausal women (mean age 64+/-8years) with a distal radius fracture treated
      by cast immobilization was scanned by HRpQCT at baseline, 3months and 2years post
      fracture. BMD and cortical and trabecular micro-architecture were measured and
      biomechanical parameters were estimated using micro finite element analysis
      (MUFEA). Additionally, markers of bone resorption and formation were measured at
      each visit. Bone parameters and turnover markers across the three visits were
      analysed using a linear mixed-effect model with Bonferroni correction. Two years
      post-fracture, a significant decrease from baseline was found in cortical BMD (
      4.2%, p<0.001), failure load (-6.1%, p=0.001), stiffness in compression (-5.7%,
      p=0.003) and bending (-6.4%, p=0.008), and bone formation (-47.6%, p=0.010). No
      significant changes from baseline were observed in total and trabecular BMD, nor
      in cortical or trabecular micro-architecture and neither in bone resorption.
      Results were similar between patients with or without adequate anti-osteoporosis
      drug treatment. We found a significant decline in BMD in the cortical but not the
      trabecular region, and a reduction in bone strength and stiffness at the contra
      lateral side two years after a distal radius fracture. These changes exceeded the
      changes that may be expected due to aging, even in the presence of adequate anti
      osteoporosis treatment.

PMID- 28502886
TI  - HMGA2, a driver of inflammation, is associated with hypermethylation in acute
      liver injury.
AB  - Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and
      inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in
      the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs
      as a driver at critical stage of hepatocellular carcinoma, herein, we
      investigated the role of HMGA2 in macrophage activation during ALI. Our study
      found that the expression of HMGA2 decreased dramatically both in KCs isolated
      from the liver in mice with ALI and in LPS-induced RAW264.7 cell lines. Moreover,
      loss- and gain-of-function studies suggested that HMGA2 could enhance the
      expression of pro-inflammatory cytokines including TNF-alpha, IL-6 and IL-1beta.
      These results indicated that HMGA2 may play an essential role in macrophage
      activation during ALI. Additionally, our results showed the expression of HMGA2
      was up-regulated when LPS-induced RAW264.7 cells were treated with 5-aza-2
      deoxycytidine. Furthermore, silencing of DNMT1, DNMT3a, DNMT3b could respectively
      prevent the down-expression of HMGA2 in LPS-induced RAW264.7 cells. In
      conclusion, HMGA2 promotes the release of pro-inflammatory cytokines through NF
      kappaB pathway, and the dysregulation of HMGA2 may involve with hypermethylation.

PMID- 28502887
TI  - Open Surgical Treatment of Secondary Aortoesophageal and Aortobronchial Fistula
      after Thoracic Endovascular Aortic Repair and Esophagocoloplasty in a Second
      Procedure.
AB  - Aortoesophageal (AEF) and aortobronchial fistula (ABF) after thoracic
      endovascular aortic repair (TEVAR) are rare complications with catastrophic
      consequences without treatment. In this case report, we presented a patient with
      AEF and ABF after TEVAR successfully treated with endograft explantation and
      replaced by Dacron graft followed by esophagectomy and left principal bronchus
      repairing. We report a patient with AEF and ABF after TEVAR who was evaluated due
      to dysphagia and chest pain followed by hematemesis and hemoptysis. Endoscopic
      examination revealed lesion of the esophageal wall with chronic abscess formation
      and stent-graft protrusion into the cavity. Patient was operated on with
      extracorporeal circulation. AEF and ABF were confirmed intraoperatively.
      Endograft was explanted and in situ reconstruction of thoracic aorta was carried
      out with tubular Dacron 22-mm prosthesis wrapped with omental flap. After aortic
      reconstruction, esophageal mucosal stripping was performed with cervical
      esophagostomy, pyloromyotomy, and Stamm-Kader gastrostomy for nutrition. In
      addition, omentoplasty of the defect in the left principal bronchus was
      performed. To re-establish peroral food intake esophagocoloplasty was carried out
      8 months after previous surgery utilizing transversosplenic segment of the colon
      and retrosternal route. In very selective cases, stent-graft explantation and in
      situ reconstruction with Dacron graft covered by omental flap followed by
      esophagectomy and bronchus repairing permit adequate debridement reducing the
      risk of mediastinitis and graft infection and allow a safe esophageal
      reconstruction in a second procedure.

PMID- 28502888
TI  - Prospective Study of Postoperative Glycemic Control with a Standardized Insulin
      Infusion Protocol after Infrainguinal Bypass and Open Abdominal Aortic Aneurysm
      Repair.
AB  - BACKGROUND: The aim of this study is to examine the effect of moderate
      postoperative glycemic control in diabetic and nondiabetic patients undergoing
      infrainguinal bypass (INFRA) or open abdominal aortic aneurysm (OAAA) repair.
      METHODS: In a single center prospective study, we investigated postoperative
      glycemic control using a standardized insulin infusion protocol after elective
      INFRA bypass (n = 53, 62%) and OAAA repair (n = 33, 38%) between January 2013 and
      March 2015. The primary end point was optimal glycemic control, defined as having
      >=85% of blood glucose values within the 80-150 mg/dL target range. Suboptimal
      glycemic control was defined as <85% of blood glucose values within the blood
      glucose target range. Secondary end points included in-hospital and 30-day
      surgical site infection (SSI) rates, composite adverse events, length of stay
      (LOS), and hospital cost. RESULTS: Optimal glycemic control was achieved more
      commonly after OAAA repair than INFRA bypass (85% vs. 64%, P = 0.04). Moderate
      hypoglycemia (<70 mg/dL) was observed in 32 (37%) patients, while severe
      hypoglycemia (<50 mg/dL) was observed in 6 (7%) patients. SSI at 30 days was more
      common after INFRA bypass (n = 15, 29%) than OAAA repair (n = 2, 6%) (P = 0.01).
      In-hospital (6% vs. 6%, P = 1.0) and 30-day (24% vs. 22%, P = 1.0) SSI rates were
      similar for optimal versus suboptimal glycemic control patients after INFRA
      bypass. In-hospital (4% vs. 0%, P = 1.0) and 30-day (4% vs. 0%, P = 1.0) SSI
      rates were similar for optimal versus suboptimal glycemic control patients after
      OAAA repair. The percentage of blood glucose > 250 mg/dL was similar for patients
      with and without SSI (3% vs. 2%, P = 0.36). Adverse cardiac and pulmonary events
      after INFRA bypass were similar between groups (9% vs. 21%, P = 0.23; 0% vs. 5%,
      P = 0.36, respectively). Adverse cardiac and pulmonary events after OAAA repair
      were similar between groups (2% vs. 0%, P = 1.0; 4% vs. 0%, P = 1.0,
      respectively). Mean LOS was significantly lower in patients with optimal glycemic
      control after INFRA bypass (4.2 vs. 7.3 days, P = 0.02). Mean LOS was similar
      after OAAA repair for patients with optimal and suboptimal control (5.8 vs. 6.4
      days, P = 0.46). Inpatient hospital costs after INFRA bypass were lower for the
      group with optimal (median $25,012, interquartile range [IQ] range $21,726
      28,331) versus suboptimal glycemic control (median $28,944, IQ range 24,773
      41,270, P = 0.02). CONCLUSIONS: Postoperative hyperglycemia is common after INFRA
      bypass and OAAA repair and can be effectively ameliorated with an insulin
      infusion protocol. The protocol was low risk with reduced LOS and cost after
      INFRA bypass. Complications including SSI were not reduced in patients with
      optimal perioperative glycemic control.

PMID- 28502889
TI  - Three-Dimensional Printing Facilitates Successful Endovascular Closure of a Type
      II Abernethy Malformation Using an Amplatzer Atrial Septal Occluder Device.
AB  - Type II Abernethy malformations, characterized by side-to-side portosystemic
      shunting with preserved intrahepatic portal venous system, have been treated with
      shunt closure surgically and endovascularly. Three-dimensional printing has been
      used to develop highly accurate patient-specific representations for surgical and
      endovascular planning and intervention. This innovation describes 3-dimensional
      printing to successfully close a flush-oriented type II Abernethy malformation
      with discrepant dimensions on computed tomography, conventional venography, and
      intravascular ultrasound, using a 12-mm Amplatzer atrial septal occluder device.

PMID- 28502890
TI  - A quantitative approach to understanding vertebrate limb morphogenesis at the
      macroscopic tissue level.
AB  - To understand organ morphogenetic mechanisms, it is essential to clarify how
      spatiotemporally-regulated molecular/cellular dynamics causes physical tissue
      deformation. In the case of vertebrate limb development, while some of the genes
      and oriented cell behaviors underlying morphogenesis have been revealed, tissue
      deformation dynamics remains incompletely understood. We here introduce our
      recent work on the reconstruction of tissue deformation dynamics in chick limb
      development from cell lineage tracing data. This analysis has revealed globally
      aligned anisotropic tissue deformation along the proximo-distal axis not only in
      the distal region but also in the whole limb bud. This result points to a need,
      as a future challenge, to find oriented molecular/cellular behaviors for
      realizing the observed anisotropic tissue deformation in both proximal and distal
      regions, which will lead to systems understanding of limb morphogenesis.

PMID- 28502891
TI  - Regulated transport of signaling proteins from synapse to nucleus.
AB  - Synapse-to-nucleus communication is essential for neural development, plasticity,
      and repair. In addition to fast electrochemical signaling, neurons employ a
      slower mechanism of protein transport from synapse-to-nucleus. This mechanism
      provides potential advantages, including the encoding of spatial information.
      Many synaptonuclear signaling proteins are transported from the postsynaptic
      compartment to the nucleus in an activity-dependent manner. The phosphorylation
      state of two such proteins, CRTC1 and Jacob, is dependent on the stimulus type.
      While most studies have focused on postsynaptic synaptonuclear communication, a
      transcriptional co-repressor, CtBP1, was recently discovered to undergo activity
      dependent translocation from the presynaptic compartment to the nucleus. Recent
      evidence indicates that synapse-to-nucleus communication could be cell type
      specific, including the identification of a distinct mechanism of excitation
      transcription coupling in inhibitory neurons.

PMID- 28502892
TI  - Biomarkers kinetics in the assessment of ventilator-associated pneumonia response
      to antibiotics - results from the BioVAP study.
AB  - PURPOSE: Our aim was to evaluate the role of biomarker kinetics in the assessment
      of ventilator-associated pneumonia (VAP) response to antibiotics. MATERIALS AND
      METHODS: We performed a prospective, multicenter, observational study to evaluate
      in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP),
      procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The
      kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time
      dependent analysis comparing survivors and non-survivors. RESULTS: During the
      study period kinetics of CRP as well as its relative changes, CRP-ratio, was
      significantly different between survivors and non-survivors (p=0.026 and p=0.005,
      respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the
      initial value while it was 96% in non-survivors. The kinetics of other studied
      variables did not distinguish between survivors and non-survivors. In survivors
      the bacterial load also decreased markedly. Adequate initial antibiotic therapy
      was associated with lower mortality (p=0.025) and faster CRP decrease (p=0.029).
      CONCLUSIONS: C-reactive protein kinetics can be used to identify VAP patients
      with poor outcome as soon as four days after the initiation of treatment. (Trial
      registration - NCT02078999; registered 3 August 2012).

PMID- 28502893
TI  - The effect of exhalation flow on endogenous particle emission and phospholipid
      composition.
AB  - Exhaled particles constitute a micro-sample of respiratory tract lining fluid.
      Inhalations from low lung volumes generate particles in small airways by the
      airway re-opening mechanism. Forced exhalations are assumed to generate particles
      in central airways by mechanisms associated with high air velocities. To increase
      knowledge on how and where particles are formed, different breathing manoeuvres
      were compared in 11 healthy volunteers. Particles in the 0.41-4.55MUm diameter
      range were characterised and sampled. The surfactant lipid
      dipalmitoylphosphatidylcholine (DPPC) was quantified by mass spectrometry. The
      mass of exhaled particles increased by 150% (95% CI 10-470) for the forced
      exhalation and by 470% (95% CI 150-1190) for the airway re-opening manoeuvre,
      compared to slow exhalations. DPPC weight percent concentration (wt%) in
      particles was 2.8wt% (95%CI 1.4-4.2) and 9.4wt% (95%CI 8.0-10.8) for the forced
      and the airway re-opening manoeuvres, respectively. In conclusion, forced
      exhalation and airway re-opening manoeuvres generate particles from different
      airway regions having different DPPC concentration.

PMID- 28502894
TI  - Soluble 1:1 complexes and insoluble 3:2 complexes - Understanding the phase
      solubility diagram of hydrocortisone and gamma-cyclodextrin.
AB  - The molecular mechanisms underlying the drug-solubilizing properties of gamma
      cyclodextrin were explored using hydrocortisone as a model drug. The BS-type
      phase-solubility diagram of hydrocortisone with gamma-cyclodextrin was thoroughly
      characterized by measuring the concentrations of hydrocortisone and gamma
      cyclodextrin in solution and the solid phase. The drug-solubilizer interaction
      was also studied by isothermal titration calorimetry from which a precise value
      of the 1:1 binding constant (K11=4.01mM-1 at 20 degrees C) was obtained. The
      formation of water-soluble 1:1 complexes is responsible for the initial increase
      in hydrocortisone solubility while the precipitation of entities with a 3:2 ratio
      of gamma-cyclodextrin:hydrocortisone is responsible for the plateau and the
      ensuing strong decrease in solubility once all solid hydrocortisone is used up.
      The complete phase-solubility diagram is well accounted for by a model employing
      the 1:1 binding constant and the solubility product of the precipitating 3:2
      entity (K32S=5.51 mM5). For such systems, a small surplus of gamma-cyclodextrin
      above the optimum concentration may result in a significant decrease in drug
      solubility, and the implications for drug formulations are briefly discussed.

PMID- 28502896
TI  - A quality by design (QbD) twin-Screw extrusion wet granulation approach for
      processing water insoluble drugs.
AB  - In this study, a Quality by Design (QbD) approach was used to identify the effect
      of formulation parameters in a twin screw wet extrusion granulation process for
      the manufacturing of ibuprofen (IBU) granules with increased dissolution rates. A
      fractional factorial Design of Experiment (DoE) was used to investigate the
      effect of the excipient composition, binder amount and liquid to solid (L/S)
      ratio (independent variables) on drug dissolution rates, median particle size
      diameter and specific surface area (dependent variables). The intra-granular
      addition of the binder in inorganic/polymer blends processed with ethanol as
      granulating liquids facilitated the formation of granules at various particle
      sizes. DoE regression analysis showed that all formulation parameters affect the
      dependent variables significantly. The enhanced dissolution rates were attributed
      not only to the IBU particle size reduction and adsorption in the porous
      inorganic network but also to the high specific surface area of the produced
      granules. Dynamic vapour sorption showed increased water absorption for granules
      with small particle size distribution and high specific surface area.

PMID- 28502895
TI  - Nanostructured lipid carriers employing polyphenols as promising anticancer
      agents: Quality by design (QbD) approach.
AB  - Cancer is one of the leading causes of death worldwide. There are several hurdles
      in cancer therapy because of side-effects which limits its usage. Nanoparticulate
      drug delivery systems have been tested against cancer in a range of scientific
      studies. In the recent years, advanced research on Nanostructured Lipid Carriers
      (NLCs) has garnered considerable attention owing to the advantages over their
      first-generation counterparts, Solid Lipid Nanoparticles (SLN). NLCs facilitate
      efficient loading of poorly water soluble drugs with simple methods of drug
      loading. Recently, there is an increased interest in polyphenols because of the
      evidence of their promising role in prevention of cancer. Polyphenols are
      produced as secondary metabolites by plants. Their role in prevention of
      development of tumors through variety of mechanisms and reduction of tumor cell
      mass has been reported. This article aims to review the science behind
      development of NLCs and role of polyphenols as promising anticancer agents.
      Principles of Quality by Design (QbD) have also been explained which are used in
      formulation-development of many nanoparticles, including NLCs, as reported in
      literature.

PMID- 28502897
TI  - A multifunctional beta-cyclodextrin-conjugate photodelivering nitric oxide with
      fluorescence reporting.
AB  - This contribution reports the design, synthesis and photochemical properties of a
      novel cationic, water soluble, beta-cyclodextrin (betaCD) conjugate integrating
      an anthracene moiety and a nitroaniline derivative within the primary side of the
      betaCD scaffold. Photoinduced energy transfer between the anthracene and the
      nitroaniline chromophores effectively suppresses the fluorescence of the
      anthracene unit. Excitation with visible light triggers the release of nitric
      oxide (NO) from the nitroaniline chromophore, accompanied to the concomitant
      revival of the anthracene fluorescence, which acts as an optical reporter for
      detecting the amount of the NO released. Furthermore, the anthracene moiety
      photogenerates singlet oxygen (1O2) sequentially to NO release. The conjugate is
      also able to accommodate hydrophobic guests within the betaCD cavity, as proven
      by using naphthalene as a model compound. In view of the key role NO and 1O2 play
      as anticancer and antibacterial species, the present betaCD derivative represents
      an intriguing candidate for further studies in biopharmaceutical research
      addressed to multimodal therapeutic applications.

PMID- 28502898
TI  - Development of modified release 3D printed tablets (printlets) with
      pharmaceutical excipients using additive manufacturing.
AB  - The aim of this study was to manufacture 3D printed tablets (printlets) from
      enteric polymers by single filament fused deposition modeling (FDM) 3D printing
      (3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from
      three different grades of the pharmaceutical excipient hypromellose acetate
      succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these
      filaments into enteric printlets incorporating up to 50% drug loading with two
      different infill percentages (20 and 100%). X-ray Micro Computed Tomography
      (Micro-CT) analysis revealed that printlets with 20% infill had cavities in the
      core compared to 100% infill, and that the density of the 50% drug loading
      printlets was higher than the equivalent formulations loaded with 5% drug. In
      biorelevant bicarbonate dissolution media, drug release from the printlets was
      dependent on the polymer composition, drug loading and the internal structure of
      the formulations. All HPMCAS-based printlets showed delayed drug release
      properties, and in the intestinal conditions, drug release was faster from the
      printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG
      > HPMCAS HG. These results confirm that FDM 3D printing makes it possible not
      only to manufacture delayed release printlets without the need for an outer
      enteric coating, but it is also feasible to adapt the release profile in response
      to the personal characteristics of the patient, realizing the full potential of
      additive manufacturing in the development of personalised dose medicines.

PMID- 28502899
TI  - The expression of P450 genes mediating fenpropathrin resistance is regulated by
      CncC and Maf in Tetranychus cinnabarinus (Boisduval).
AB  - Although overexpression of genes encoding detoxification enzymes is a well-known
      mechanism of pesticide resistance of mites, the regulators involved in this
      process are still illiterate. Previous studies in our laboratory demonstrated
      that the overexpression of six P450 genes contributes to fenpropathrin resistance
      in T. cinnabarinus. In this study, six transcription factor genes that likely
      regulate the expression of P450 genes were identified and characterized.
      Quantitative PCR (qPCR) analysis showed that three transcription factor genes
      were highly expressed in a fenpropathrin-resistant (FeR) strain of T.
      cinnabarinus. The cap 'n' collar isoform C (CncC) and muscle aponeurosis
      fibromatosis (Maf) family transcription factors were identified as the key
      regulator of P450 genes by RNA interference (RNAi). Furthermore, research on the
      promoters of these P450 genes using reporter assays identified that CncC and Maf
      influence the susceptibility of T. cinnabarinus to fenpropathrin through
      regulating the expression of P450 genes. This study increases our understanding
      of the molecular mechanisms underlying the regulation of P450 genes involved in
      detoxification of acaricides in T. cinnabarinus.

PMID- 28502900
TI  - Nuclear morphometry in histological specimens of canine prostate cancer:
      Correlation with histological subtypes, Gleason score, methods of collection and
      survival time.
AB  - Ten normal prostates, 22 benign prostatic hyperplasia (BPH) and 29 prostate
      cancer (PC) were morphometrically analyzed with regard to mean nuclear area
      (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND), coefficient of
      variation of the nuclear area (NACV), mean nuclear diameter maximum (MDx), mean
      nuclear diameter minimum (MDm), mean nuclear form ellipse (MNFe) and form factor
      (FF). The relationship between nuclear morphometric parameters and histological
      type, Gleason score, methods of sample collection, presence of metastases and
      survival time of canine PC were also investigated. Overall, nuclei from
      neoplastic cells were larger, with greater variation in nuclear size and shape
      compared to normal and hyperplastic cells. Significant differences were found
      between more (small acinar/ductal) and less (cribriform, solid) differentiated
      PCs with regard to FF (p<0.05). MNA, MNP, MND, MDx, and MDm were significantly
      correlated with the Gleason score of PC (p<0.05). MNA, MNP, MDx and MNFe may also
      have important prognostic implications in canine prostatic cancer since
      negatively correlated with the survival time. Biopsy specimens contained nuclei
      that were smaller and more irregular in comparison to those in prostatectomy and
      necropsy specimens and therefore factors associated with tissue sampling and
      processing may influence the overall morphometric evaluation. The results
      indicate that nuclear morphometric analysis in combination with Gleason score can
      help in canine prostate cancer grading, thus contributing to the establishment of
      a more precise prognosis and patient's management.

PMID- 28502902
TI  - Retinoic acid-mediated anti-inflammatory responses in equine immune cells
      stimulated by LPS and allogeneic mesenchymal stem cells.
AB  - Retinoic acid (RA), an active metabolite of vitamin A, has shown potential
      therapeutic immunomodulatory properties. Allogeneic mesenchymal stem cells (MSCs)
      based therapy is an effective approach to induce tissue healing and regeneration
      in many equine orthopedic conditions. However, MSCs-based therapies induced
      inflammatory responses in vivo. This study aimed to: 1. Determine the effect of
      RA cell culture treatment on inflammatory responses of lipopolysaccharides (LPS)-
      and allogeneic MSCs-stimulated peripheral blood mononuclear cells (PBMCs). 2.
      Determine the effect of RA on stimulated MSCs viability and morphology.
      Allogeneic MSCs-stimulated PBMCs had significant decreases in the anti
      inflammatory cytokines (IL-10, IL-1ra, TGF-beta1), increases in the pro
      inflammatory mediators (IL-1beta, IL-6, TNF-alpha, SAA), and increases of CD14
      and MHC II percent positive cells compared to LPS- and non-stimulated PBMCs.
      Retinoic acid treatment of LPS- and allogeneic MSCs-stimulated PBMCs
      counterbalanced the induced inflammatory responses. Moreover, RA significantly
      improved the viability and morphology of stimulated MSCs. These findings
      highlighted the potential complications of equine allogeneic MSCs-based therapies
      and the immuno-modulatory effect of RA on equine stimulated cells. In conclusion,
      the use of RA to ameliorate allogeneic MSCs therapy associated inflammation may
      offer advantages that would require further investigations.

PMID- 28502901
TI  - Neuraminidase activity of blue eye disease porcine rubulavirus: Specificity,
      affinity and inhibition studies.
AB  - Porcine rubulavirus (PorPV), also known as La Piedad Michoacan Virus (LPMV)
      causes encephalitis and reproductive failure in newborn and adult pigs,
      respectively. The hemagglutinin-neuraminidase (HN) glycoprotein is the most
      exposed and antigenic of the virus proteins. HN plays central roles in PorPV
      infection; i.e., it recognizes sialic acid-containing cell receptors that mediate
      virus attachment and penetration; in addition, its neuraminidase (sialic acid
      releasing) activity has been proposed as a virulence factor. This work describes
      the purification and characterization of PorPV HN protein (isolate PAC1). The
      specificity of neuraminidase is restricted to sialyl(alpha2,3)lactose (3SL). HN
      showed typical Michaelis-Menten kinetics with fetuin as substrate (km=0.029MUM,
      Vmax=522.8nmolmin-1mg-1). When 3SL was used as substrate, typical cooperative
      kinetics were found (S50=0.15MUM, Vmax=154.3nmolmin-1mg-1). The influenza
      inhibitor zanamivir inhibited the PorPV neuraminidase with IC50 of 0.24MUM. PorPV
      neuraminidase was activated by Ca2+ and inhibited by nucleoside triphosphates
      with the level of inhibition depending on phosphorylation level. The present
      results open possibilities to study the role of neuraminidase in the
      pathogenicity of PorPV infection and its potential inhibitors.

PMID- 28502903
TI  - Subclinical bovine vaccinia: An important risk factor in the epidemiology of this
      zoonosis in cattle.
AB  - Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV) that mainly
      affects lactating cows and dairy farm milkers. The epidemiological role(s) of
      other cattle categories such as dry cows, bulls, and heifers in BV remains
      unclear. This study was performed to investigate VACV in affected dairy cattle
      herds and perifocal farms during an outbreak in Brazil. Crusts from lesions of
      cows' teats were collected from all farms with BV outbreaks. Milk, feces, blood,
      and serum were collected from symptomatic and asymptomatic lactating cows. Blood
      and serum were also sampled from other cattle categories (calves, heifers, dry
      cows, and bulls). The samples were tested for VACV by PCR, and to confirm VACV
      viability, VACV-positive samples were inoculated in BSC-40 cells and stained
      using immunoperoxidase. Neutralizing antibodies were investigated using plaque
      reduction neutralization test. Viral DNA was detected in milk, blood, and feces
      samples of symptomatic and asymptomatic dairy cows and in blood samples from
      other cattle categories on farms with and without confirmed BV outbreak. In
      affected farms, viable virus was identified in feces and milk samples from
      lactating cows and in blood samples from asymptomatic dry cows. Viable VACV was
      also identified in feces from lactating cows and one bull's blood sample from
      perifocal farms. Neutralizing antibodies were detected in 81.6% of the herds
      affected by BV and in 53.8% of the herds on perifocal farms. The presented data
      indicate a potential source of viral dissemination, which contributes to the
      persistence and spread of VACV in the environment.

PMID- 28502904
TI  - Src and Syk contribute to the anti-inflammatory activities of Achyranthes aspera
      ethanolic extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Nuclear factor-kappa B (NF-kappaB) plays pivotal
      roles in inflammation. Src and Syk are two tyrosine kinases that act upstream of
      NF-kappaB signaling. Although Achyranthes aspera L. (A. aspera) has been used as
      a traditional medicine to treat fevers and inflammatory ailments and heal wounds,
      the molecular mechanisms of its anti-inflammatory actions are not yet fully
      understood. MATERIALS AND METHODS: In this study, we evaluated the anti
      inflammatory effect of A. aspera ethanol extract (Aa-EE). To determine the
      mechanism by which Aa-EE dampens the inflammatory response, nitric oxide (NO)
      production and the mRNA expression levels of tumor necrosis factor (TNF)-alpha
      and inducible nitric oxide synthase (iNOS) were examined by Griess assay and RT
      PCR. Luciferase assays and immunoblotting were also conducted to examine how Aa
      EE regulates the NF-kappaB pathway. RESULTS: Aa-EE reduced NO production up to
      60% without any cytotoxicity. This extract was found to downregulate the mRNA
      expression levels of inflammatory genes. Aa-EE blocked NF-kappaB promoter
      activity induced by both TNF-alpha and adaptor molecule MyD88 (about 70% and 40%,
      respectively). Moreover, nuclear translocation of p65 and IkappaBalpha
      phosphorylation were also inhibited. Furthermore, Aa-EE inactivated two upstream
      signaling molecules, the Src and Syk kinases. In accordance with these data, the
      kinase activities of Src and Syk were decreased by 50% and 80%, respectively. The
      anti-inflammatory action of Aa-EE was also confirmed in a gastritis model.
      CONCLUSION: Our data suggest that Aa-EE targets NF-kappaB to exert its anti
      inflammatory properties by suppressing Src and Syk. Therefore, our study raises
      the possibility that this extract can be developed as a novel natural anti
      inflammatory remedy.

PMID- 28502905
TI  - Inhibition of proinflammatory mediators by coumaroyl lupendioic acid, a new
      lupane-type triterpene from Careya arborea, on inflammation-induced animal model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Careya arborea Roxb. (Lecythidaceae) is a large
      tree found throughout India in deciduous forests and grasslands. C. arborea is
      traditionally used in tumors, inflammation, anthelmintic, bronchitis, epileptic
      fits, astringents, antidote to snake-venom, skin disease, diarrhea, dysentery
      with bloody stools, dyspepsia, ulcer, tooth ache, and ear pain. AIM OF THE STUDY:
      In our previous work, the methanolic extract of Careya arborea stem bark showed
      significant anti-inflammatory activity. As a continuity of that work, this study
      aimed at the isolation and evaluation of the anti-inflammatory effect of
      coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem
      bark. Further, to give an insight into the underlying mechanism of action of the
      compound on the modulation of proinflammatory mediators. MATERIALS AND METHODS:
      Methanolic extract of Careya arborea stem bark was suspended in water, and
      sequentially fractionated with n-hexane and ethyl acetate. Further ethyl acetate
      fraction was subjected to medium pressure liquid chromatography (MPLC) to isolate
      the active molecules. The isolated compounds were characterized by the various
      spectral techniques namely UV, IR, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HMBC and
      Mass spectral techniques. In vitro COX-1 and COX-2 enzyme inhibition assays using
      human whole blood was performed to investigate the inhibitory effect of the
      isolated compounds. The resulted potent COX-2 inhibitor of the isolated
      constituents compound 5, designated as coumaroyl lupendioic acid (CLA), was
      investigated in carrageenan induced inflammation and its effect was also compared
      with betulinic acid (BA) at the doses of 10 and 20mgkg-1, p.o. using indomethacin
      and celecoxib (10 and 20mgkg-1, p.o., respectively) as reference drugs. The
      effect of CLA on the production of NO, MPO, PGE2, TNF-alpha, IL-1beta and IL-6
      were assessed. In addition, the histopathology and immunohistochemistry (NF-?B,
      COX-2 and TNF-alpha protein expression) in paw tissues were also carried out.
      RESULTS: The chromatographic fractionation of the methanolic extract resulted in
      isolation of six new derivatives of lupane type triterpenes for the first time
      from the stem bark of C. arborea; 3beta-hydroxy-lup-5,20 (29),21-trien-28-oic
      acid (Compound 1), 1, 3, 13, 16-tetrahydroxy-lup-9(11), 20(29)-diene-28-oic acid
      (Compound 2), 1, 7-di hydroxy betulinic acid (Compound 3), 3beta-O
      dihydrocinnamyl betulinic acid (Compound 4), 3beta-O-trans-coumaryl-lup-6, 9(11),
      20(29)-triene-27, 28-dioic acid (Compound 5), 16beta-hydroxy-2, 3-seco-lup-5,
      20(29)-dien-2, 3, 28-trioic acid (Compound 6). Among the all isolated compounds
      3beta-O-trans-coumaryl-lup-6, 9(11), 20(29)-triene-27, 28-olioic acid designated
      as coumaroyl lupendioic acid (CLA) showed higher COX-2 selectivity which is
      comparable to reference drug (celecoxib). CLA significantly reduced carrageenan
      induced inflammation whereas CLA revealed greater effect as compared to BA at the
      similar corresponding doses. Moreover, CLA significantly inhibited pro
      inflammatory mediators elevated by carrageenan. CLA also preserved the tissue
      architecture as evidenced by the histopathology. Furthermore, immunohistochemical
      studies revealed that CLA significantly down regulated NF-?B, COX-2 and TNF-alpha
      protein expression. CONCLUSION: The study gives an insight into the molecular
      mechanisms of coumaroyl lupendioic acid and suggests that the down-regulations of
      proinflammatory mediators provide credence to the ethno botanical use of the
      plant in the management of inflammation.

PMID- 28502906
TI  - Anti-inflammatory effects of Forsythia suspensa in dextran sulfate sodium-induced
      colitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa Fructus (FS) is used to treat
      various inflammatory disorders in traditional Oriental medicine, including
      gastrointestinal diseases, but its therapeutic potential in ulcerative colitis is
      unclear. Thus, we investigated any potential therapeutic effects of FS against
      intestinal inflammation and the bioactive constituents in FS. MATERIALS AND
      METHODS: After the induction of colitis using 3% dextran sulfate sodium, FS
      (100mg/kg/day) was administered orally during the experimental period. We
      evaluated body weight, bloody diarrhea, colon length, and pro-inflammatory
      cytokine levels. Subsequently, the bioactive constituents of FS were identified
      using UPLC/MS/MS. RESULTS: FS significantly decreased the body weight loss, colon
      length shortening, and tumor necrosis factor-alpha and interleukin-6 elevations
      induced by colitis compared with the negative control (P < 0.05). Moreover, FS
      improved the colitis-induced histopathological damage to the colon, including
      epithelial necrosis, infiltration of inflammatory cells, ulceration, and
      submucosal edema. In phytochemical analyses, 7 flavonoids, 9 lignans, 13
      phenolics, and 2 triterpenes were identified by comparison with the retention
      times and mass fragmentations of authentic standards. CONCLUSIONS: We
      demonstrated beneficial effects of FS and its constituents, suggesting their
      potential for treatment of intestinal inflammation. These data could provide
      useful information for managing ulcerative colitis.

PMID- 28502907
TI  - Neuropathic and inflammatory antinociceptive effects and electrocortical changes
      produced by Salvia divinorum in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum is a medicinal plant
      traditionally used in hallucinogenic ethnopharmacological practices and for its
      analgesic and antinflammatory properties. Its active compounds include diterpenes
      known as salvinorins which act as potent kappa opioid receptor agonists. AIM OF
      THE STUDY: Given its effects in acute animal models of pain, as well as its
      antinflammatory attributes, we decided to investigate the analgesic effects of an
      SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra
      plantar carrageenan) pain models in rats. We also determined in this study the
      electrocorticographic changes to correlate similar hallucinogenic state and
      behavior as those produced in humans. MATERIAL AND METHODS: Mechanical and
      thermonociceptive responses, plantar test and von Frey assay, respectively, were
      measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal
      administration of saline or an hydroponic SD extract. We also evaluated
      carbamazepine and celecoxib, as gold reference drugs, to compare its
      antinociceptive effects. RESULTS: Our results showed that administration of SD
      extract induced antialgesic effects in both neuropathic and inflammatory pain
      models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid
      receptor antagonist). Moreover, it was observed an increase of the anterior power
      spectral density and a decrease in the posterior region as electrocorticographic
      changes. CONCLUSION: The present investigation give evidence that SD is capable
      to reduce algesic response associated to neuropathic and inflammatory
      nociception. This study support therapeutic alternatives for a disabling health
      problem due to the long term pain with high impact on population and personal and
      social implications.

PMID- 28502908
TI  - Chronic administration of antioxidant resin from Virola oleifera attenuates
      atherogenesis in LDLr -/- mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Virola oleifera (Schott) A. C. Smith,
      Myristicaceae has been largely used in traditional folk medicine in Brazil as an
      anti-inflammatory agent and our previous data indicated the antioxidant
      properties in other oxidative stress-related models. However, its effects on
      atherosclerosis (AT) are not yet investigated. AIMS OF THE STUDY: To evaluate the
      influence of resin from Virola oleifera (RV) on progression of AT in LDLr-/-
      mice. MATERIALS AND METHODS: LDLr-/- mice were divided into 4 groups: 1) The ND
      group received a normal diet without treatment. 2) The HD group received a high
      fat diet without treatment. 3) The HD-V50 received a high-fat diet and was orally
      treated with RV at 50mg/Kg. 4) The HD-V300 received a high-fat diet and was
      orally treated with RV at 300mg/Kg. After 4 weeks, blood was collected to
      quantify biochemical parameters and ROS total and the aorta was removed to
      measure the lipid deposition by en face analysis. The liver was also collected to
      determine total lipids and lipid and protein oxidation. In order to investigate
      in more detail the contributions of RV in the vascular structure, we carried out
      the in vitro tests using four cellular types: macrophages, fibroblasts, vascular
      smooth muscle and endothelial cells. RESULTS: We showed that the chronic
      treatment of RV at both doses reduced vascular lipid accumulation (~50%, p<0.05),
      probably through systemic and hepatic antioxidant effects, independent of
      dyslipidemia. Moreover, the in vitro assay results demonstrated that RV develops
      antioxidant properties on the vascular smooth muscle and endothelial cells,
      reinforcing the protective role of RV in progression of AT. LPS-stimulated
      macrophages treated with RV resulted in a significant reduction of NO production
      in a concentration-dependent manner. CONCLUSIONS: Chronic treatment with RV
      diminishes lipid deposition in atherosclerotic mice, which may be justified, at
      least in part, by antioxidant systemic and local mechanisms, reinforcing the
      protective role this resin in the setting of vascular lipid deposition,
      independent of hypercholesterolemia.

PMID- 28502909
TI  - Character-level neural network for biomedical named entity recognition.
AB  - Biomedical named entity recognition (BNER), which extracts important named
      entities such as genes and proteins, is a challenging task in automated systems
      that mine knowledge in biomedical texts. The previous state-of-the-art systems
      required large amounts of task-specific knowledge in the form of feature
      engineering, lexicons and data pre-processing to achieve high performance. In
      this paper, we introduce a novel neural network architecture that benefits from
      both word- and character-level representations automatically, by using a
      combination of bidirectional long short-term memory (LSTM) and conditional random
      field (CRF) eliminating the need for most feature engineering tasks. We evaluate
      our system on two datasets: JNLPBA corpus and the BioCreAtIvE II Gene Mention
      (GM) corpus. We obtained state-of-the-art performance by outperforming the
      previous systems. To the best of our knowledge, we are the first to investigate
      the combination of deep neural networks, CRF, word embeddings and character-level
      representation in recognizing biomedical named entities.

PMID- 28502911
TI  - Fake News, Alternative Facts, Post-Truths, Misinformation, Misinterpretation-and
      Other Challenges Associated With Knowledge Generation.

PMID- 28502910
TI  - Balancing volume and duration of information consumption by physicians: The case
      of health information exchange in critical care.
AB  - BACKGROUND: The realization of the potential benefits of health information
      exchange systems (HIEs) for emergency departments (EDs) depends on the way these
      systems are actually used. The attributes of volume of information and duration
      of information processing are important for the study of HIE use patterns in the
      ED, as cognitive load and time constraints may result in a trade-off between
      these attributes. Experts and non-experts often use different problem-solving
      strategies, which may be consequential for their system use patterns. Little
      previous research focuses on the trade-off between volume and duration of system
      use or on the factors that affect it, including user expertise. OBJECTIVES: This
      study aims at exploring the trade-off of volume and duration of use, examining
      whether this relationship differs between experts and non-experts, and
      identifying factors that are associated with use patterns characterized by volume
      and duration. METHODS: The research objectives are pursued in the context of
      critically-ill patients, treated at a busy ED in the period 2010-2012. The
      primary source of internal and external data is an HIE linked to 14 hospitals,
      over 1300 clinics, and other clinical facilities. We define four use profiles
      based on the attributes of duration and volume: quick and basic, quick and deep,
      slow and basic, and slow and deep. The volume and duration of use are computed
      using HIE log files as the number of screens and the time per screen,
      respectively. Each session is then classified into a specific profile based on
      distances from predefined profile centroids. Experts are physicians that are
      board-certified in emergency medicine. We test the distribution of use profiles
      and their associations with multiple variables that describe the patient,
      physician, situation, information available in the HIE system, and use dynamics
      within the encounter. RESULTS: The quick and basic profile is the most prevalent.
      While available admission summaries are associated with quick and basic use, lab
      and imaging results are associated with slower or deeper use. Physicians who are
      the first to use the system or are sole users during an encounter are less
      inclined to quick and deep use. These effects are intensified for experts.
      DISCUSSION: A trade-off between volume and duration is identified. While system
      use is overall similar for experts and non-experts, the circumstances in which a
      certain profile is more likely to be observed vary across these two groups.
      Information availability and multiple-physician dynamics within the encounter
      emerge as important for the prediction of use profiles. The findings of this
      study provide implications for the design, implementation, and research of HIE
      use.

PMID- 28502912
TI  - Thinking Styles and Quality of University Life Among Deaf or Hard of Hearing and
      Hearing Students.
AB  - The authors explored how thinking styles relate to quality of university life
      among deaf or hard of hearing (DHH) and hearing university students in mainland
      China. The first of two studies affirmed the validity and reliability of a
      modified version of the Quality of University Life Measure (QULM; Sirgy,
      Grezskowiak, & Rahtz, 2007) among 833 university students (366 DHH, 467 hearing).
      The second investigated relationships between thinking styles and quality of
      university life; the Thinking Styles Inventory-Revised II (Sternberg, Wagner, &
      Zhang, 2007) and modified QULM were administered to 542 students (256 DHH, 286
      hearing). Students scoring higher on Type I styles (i.e., more creativity
      generating, less structured, cognitively more complex) tended toward greater
      satisfaction with university life; those scoring higher on Type II (i.e., more
      norm-favoring, more structured, cognitively more simplistic) tended toward less
      satisfaction. Contributions, limitations, and implications of the research are
      discussed.

PMID- 28502913
TI  - Scaffolding the Communication of People With Congenital Deafblindness: An
      Analysis of Sequential Interaction Patterns.
AB  - The High Quality Communication intervention aims to stimulate interpersonal
      communication between individuals with congenital deaf-blindness (CDB) and their
      social partners. Found effective in multiple-case experiments, the intervention
      is based on Trevarthen's theory of inter-subjective development (Braten &
      Trevarthen, 2007), which describes children's innate and developing ability to
      share subjective states in interpersonal communication and social partners'
      mediating role in this development. One implication of this theory is that social
      partners can support the emergence of higher-complexity communication behaviors
      in individuals who are still developing these behaviors. To test this
      proposition, communication patterns between individuals with CDB and their
      parents, teachers, and professional caregivers were analyzed. Analysis of two
      event sequences of communicative behaviors showed a highly significant
      correspondence between the behavior of the social partner and the subsequent
      behavior of the individual with CDB, confirming that social partners can scaffold
      higher-complexity communication within interpersonal communication.

PMID- 28502914
TI  - Introduction: Sign Language, Sustainable Development, and Equal Opportunities.

PMID- 28502915
TI  - A Dialogue on the Multiple Facets of Sustainability.
AB  - This chapter contains excerpts from a conversation among the contributors to Sign
      Language, Equal Opportunities, and Sustainable Development (De Clerck & Paul,
      2016) during a workshop that preceded the International Conference on Sign
      Language, Sustainable Development, and Equal Opportunities (Ghent University,
      Belgium, April 2014). The objective of the conversation was to illustrate an open
      ended, dialogical approach that added an interactive component to the book and
      inspired further thoughts and exchanges. Videos of the conversation were posted
      online by the European Union of the Deaf at http://www.eud.eu/news/university
      gent/.

PMID- 28502916
TI  - Perspectives on the Sign Language Factor in Sub-Saharan Africa: Challenges of
      Sustainability.

PMID- 28502918
TI  - Ability of the Ankle Brachial Index and Brachial-Ankle Pulse Wave Velocity to
      Predict the 3-Month Outcome in Patients with Non-Cardioembolic Stroke.
AB  - AIM: Both the ankle brachial index (ABI) and brachial-ankle pulse wave velocity
      (baPWV) are surrogates for atherosclerosis. In this study, we aimed to evaluate
      the ability of ABI and baPWV to predict stroke outcome in patients with first
      ever non-cardioembolic stroke. METHODS: This study included consecutive patients
      with first-ever non-cardioembolic stroke admitted within 1 week after onset to
      Ota Memorial Hospital between January 2011 and December 2013. Baseline
      characteristics and National Institutes of Health stroke scale scores at
      admission were noted. ABI and baPWV were evaluated within 5 days of admission.
      The patients were categorized according to ABI (cut-off 0.9) and baPWV (cut-off
      1870 cm/s) determined using the receiver operation curve for poor outcome.
      Clinical outcomes were defined based on the modified Rankin scale (mRS) scores 3
      months after stroke onset as good (0 and 1) or poor (2-6). RESULTS: A total of
      861 patients were available for evaluation. ABI <0.9 and baPWV >1870 cm/s were
      associated with poor outcome in the univariate analysis (p<0.001 and p<0.001,
      respectively). After adjusting for factors that showed differences between
      groups, ABI <0.9 was associated with poor outcome. Among patients with ABI >=
      0.9, higher baPWV showed a slight association with poor outcome after adjustment
      [odds ratio 1.46 (95% CI 0.95-2.27)]. CONCLUSION: Our study suggests that the
      stroke outcome can be predicted using ABI and to an extent using baPWV when ABI
      >= 0.9 in patients with non-cardioembolic stroke.

PMID- 28502920
TI  - Endostatin as a Biomarker of Basement Membrane Degradation.

PMID- 28502919
TI  - Adiponectin and T-Cadherin: a Tree for Biomarkers in ST-Elevation or Non-ST
      Elevation Myocardial Infarction.

PMID- 28502917
TI  - The Role of Heparin Cofactor II in the Regulation of Insulin Sensitivity and
      Maintenance of Glucose Homeostasis in Humans and Mice.
AB  - AIM: Accelerated thrombin action is associated with insulin resistance. It is
      known that upon activation by binding to dermatan sulfate proteoglycans, heparin
      cofactor II(HCII) inactivates thrombin in tissues. Because HCII may be involved
      in glucose metabolism, we investigated the relationship between plasma HCII
      activity and insulin resistance. METHODS AND RESULTS: In a clinical study,
      statistical analysis was performed to examine the relationships between plasma
      HCII activity, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and
      homeostasis model assessment-insulin resistance (HOMA-IR) in elderly Japanese
      individuals with lifestyle-related diseases. Multiple regression analysis showed
      significant inverse relationships between plasma HCII activity and HbA1c
      (p=0.014), FPG (p=0.007), and HOMA-IR (p= 0.041) in elderly Japanese subjects. In
      an animal study, HCII+/+ mice and HCII+/- mice were fed with a normal diet or
      high-fat diet (HFD) until 25 weeks of age. HFD-fed HCII+/- mice exhibited larger
      adipocyte size, higher FPG level, hyperinsulinemia, compared to HFD-fed HCII+/+
      mice. In addition, HFD-fed HCII+/- mice exhibited augmented expression of
      monocyte chemoattractant protein-1 and tumor necrosis factor, and impaired
      phosphorylation of the serine/threonine kinase Akt and AMP-activated protein
      kinase in adipose tissue compared to HFD-fed HCII+/+ mice. The expression of
      phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was also enhanced in
      the hepatic tissues of HFD-fed HCII+/- mice. CONCLUSIONS: The present studies
      provide evidence to support the idea that HCII plays an important role in the
      maintenance of glucose homeostasis by regulating insulin sensitivity in both
      humans and mice. Stimulators of HCII production may serve as novel therapeutic
      tools for the treatment of type 2 diabetes.

PMID- 28502921
TI  - Umbilical Cord MSCs Reverse D-Galactose-Induced Hepatic Mitochondrial Dysfunction
      via Activation of Nrf2/HO-1 Pathway.
AB  - Mitochondria are the central hubs for cellular bioenergetics and are crucial to
      cell survival. It is well accepted that compromised mitochondrial function is
      linked with hepatocytes injury and contribute to progression of liver diseases.
      Despite the therapeutic potential of mesenchymal stem cells (MSCs)
      transplantation on hepatic disorders have been extensively investigated, the
      effects of MSCs on mitochondrial function in liver injury models remain unknown.
      Here we investigated the effects of treatment with umbilical cord (UC) MSC in a
      rat model of D-galactose (D-Gal) induced liver injury, characterized by organ
      damage, oxidative stress and mitochondrial dysfunction. Our results showed that
      UC-MSCs treatment significantly alleviated histological lesion and attenuated the
      elevation of liver biochemical markers, demonstrating its protective effects on D
      Gal induced hepatic disorders. Mitochondria isolated from the liver of D-Gal
      models exhibited decreased antioxidant capacity as well as compromised
      bioenergetics functions, as shown by a loss of mitochondrial membrane potential,
      elevation of reactive oxygen species (ROS) production, reduction of mitochondrial
      respiration complexes and ATP decrement. Treatment of rats with UC-MSCs
      remarkably blunted these changes and rescued mitochondrial efficiency.
      Mechanistically, we found that the protective potential of UC-MSCs administration
      was mediated by nuclear factor-E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1)
      pathway, but not FOXO3a pathway. In conclusion, the attenuating effects of UC
      MSCs on hepatic damage partially rely on normalizing mitochondrial function and
      preventing a state of energetic deficit via activation of Nrf2/HO-1 pathway.

PMID- 28502922
TI  - Design, Synthesis, and Structure-Activity Relationship Study of Epoxysuccinyl
      Peptide Derivatives as Cathepsin B Inhibitors.
AB  - Cathepsin B is a lysosomal cysteine protease involved in many diseases. The
      present research demonstrates that derivatives of epoxysuccinyl-peptide are
      effective and selective cathepsin B inhibitors. We synthesized a series of
      epoxysuccinyl-peptide derivatives based on the well-known cathepsin B inhibitor
      E64d. Specifically, we substituted the 2-methylpropane group at the R1 position
      of E64d with a sulfane, such as ethyl(methyl) sulfane or benzyl(methyl) sulfane.
      We also designed and synthesized a library of molecules with various substituents
      at the R2 position of E64d to replace 2-methylbutane. By studying the structure
      activity relationships of these newly synthesized molecules as cathepsin B
      inhibitors, we demonstrated that substituting ethyl(methyl) sulfane for 2
      methylbutane (R2) of E64d improves the inhibitory activity and selectivity for
      cathepsin B inhibition. Our new cathepsin B inhibitors were highly effective and
      selective.

PMID- 28502923
TI  - G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in
      the center of the circadian clock [Review].
AB  - G-protein-coupled receptors (GPCRs) constitute an immensely important class of
      drug targets with diverse clinical applications. There are still more than 120
      orphan GPCRs whose cognate ligands and physiological functions are not known. A
      set of circadian pacemaker neurons that governs daily rhythms in behavior and
      physiology resides in the suprachiasmatic nucleus (SCN) in the brain. Malfunction
      of the circadian clock has been linked to a multitude of diseases, such as
      sleeping disorders, obesity, diabetes, cardiovascular diseases, and cancer, which
      makes the clock an attractive target for drug development. Here, we review a
      recently identified role of Gpr176 in the SCN. Gpr176 is an SCN-enriched orphan
      GPCR that sets the pace of the circadian clock in the SCN. Even without known
      ligand, this orphan receptor has an agonist-independent basal activity to reduce
      cAMP signaling. A unique cAMP-repressing G-protein subclass Gz is required for
      the activity of Gpr176. We also provide an overview on the circadian regulation
      of G-protein signaling, with an emphasis on a role for the regulator of G-protein
      signaling 16 (RGS16). RGS16 is indispensable for the circadian regulation of cAMP
      in the SCN. Developing drugs that target the SCN remains an unfulfilled
      opportunity for the circadian pharmacology. This review argues for the potential
      impact of focusing on GPCRs in the SCN for the purpose of tuning the body clock.

PMID- 28502924
TI  - High Time to Upgrade the Clinical Joint Examination with Complementary
      Musculoskeletal Ultrasound -From the Clinician's Finger to the Ultrasound
      Transducer.

PMID- 28502925
TI  - Therapeutic Response to Twice-daily Rabeprazole on Health-related Quality of Life
      and Symptoms in Patients with Refractory Reflux Esophagitis: A Multicenter
      Observational Study.
AB  - Objective To investigate the effect of twice-daily rabeprazole doses on health
      related quality of life in refractory patients. Methods and Patients Reflux
      esophagitis patients with an insufficient response to once-daily proton pump
      inhibitor therapy (Los Angeles Classification grade A-D) received rabeprazole 10
      mg or 20 mg twice daily for 8 weeks. The health-related quality of life (SF-8TM)
      and symptoms, using the Frequency Scale for the Symptoms of Gastroesophageal
      reflux disease, were evaluated before treatment and at weeks 4 and 8. Endoscopy
      was performed at baseline and at weeks 8 and 32 where possible. The rabeprazole
      dose was determined by the attending physician. Results There were 1,796 patients
      analyzed for the efficacy of the twice-daily treatment. Of these cases, 1,462
      were treated with rabeprazole 10 mg twice daily, and 334 were treated with
      rabeprazole 20 mg twice daily. The factors that affected the selection of the
      twice-daily rabeprazole dose by physicians were evaluated, and as expected,
      "endoscopic findings when treatment was started" had a strong effect on the
      selection of the rabeprazole dose. With both regimens, health-related quality of
      life and subjective symptoms were significantly improved at weeks 4 and 8
      compared to baseline (p<0.001). The recurrence rate of erosive esophagitis at
      week 32 was 9.7% in rabeprazole twice daily-treated patients and 28.4% in proton
      pump inhibitor (PPI) once daily-treated patients. Both regimens were well
      tolerated. Conclusion Twice-daily treatment with rabeprazole improved the
      subjective symptoms and health-related quality of life in patients with
      refractory reflux esophagitis more effectively than the standard once-daily dose.

PMID- 28502926
TI  - The Evaluation of the Sputum Antigen Kit in the Diagnosis of Pneumococcal
      Pneumonia.
AB  - Objective A previously developed sputum antigen detection kit for Streptococcus
      pneumoniae enabled the early diagnosis of pneumococcal pneumonia using sputum
      samples. We conducted a prospective study to compare the sensitivity of the
      sputum and urinary antigen kits. Methods Pneumonia patients who were treated from
      April 2014 to September 2015 were recruited for the present study. Patients with
      pneumococcal pneumonia who could not participate in the prospective arm of the
      study were analyzed in the retrospective arm. Results Nine of the 69 participants
      in the prospective study had pneumococcal pneumonia. The sputum antigen kit
      results correlated well with the sputum culture results. The sensitivity of the
      sputum antigen kit was 88.9% (8/9), which was higher than that of the urinary
      antigen kit (5/9; 55.6%). When patients from the retrospective arm of the study
      were included, the sensitivity of the sputum culture was 93.5% (29/31), which was
      significantly higher than that of the urinary antigen kit (19/31; 60.6%). False
      positives were obtained using the sputum antigen kit in four cases. Three of the
      four false positives were suspected to have resulted from the administration of
      antibiotics prior to the use of the kit; the remaining case likely occurred due
      to a false reaction to S. milleri-induced pyothorax. Conclusion Collectively, our
      findings suggest that the sputum antigen kit has a higher sensitivity for
      detecting S. pneumoniae than the urinary antigen kit. However, the prior
      administration of antibiotics can render the sputum culture results negative or
      lead to a false-positive result.

PMID- 28502927
TI  - Mizoribine Synchronized Methotrexate Therapy should be Considered when Treating
      Rheumatoid Arthritis Patients with an Inadequate Response to Various Combination
      Therapies.
AB  - Objective The objective of this study was to confirm the efficacy of low-dose
      mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, as part of
      synchronized methotrexate (MTX) therapy for rheumatoid arthritis (RA) patients
      with an inadequate response to various combination therapies of MTX, other
      synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs.
      Methods Low-dose MZR was administered to 56 uncontrolled RA patients being
      treated with MTX and various biological DMARDs. The observation period was 12
      months, and the disease activity was evaluated based on the Disease Activity
      Score in 28 joints (DAS28)-ESR, Simplified Disease Activity Index (SDAI) and
      serum MMP-3 level. Results All of the disease activity indices were significantly
      improved within three months, and the serum MMP-3 levels were also significantly
      decreased around four months after starting low-dose MZR therapy. No patients
      experienced any adverse effects. Conclusion The present preliminary findings
      suggest that low-dose MZR therapy with MTX should be considered for the treatment
      of RA patients with an inadequate response to various combination therapies
      including MTX, other synthetic DMARDs and biological DMARDs or in whom increasing
      the dose of MTX is difficult for reasons such as adverse effects and
      complications.

PMID- 28502928
TI  - Endoscopic Submucosal Dissection for Depressed-type Early Adenocarcinoma of the
      Terminal Ileum.
AB  - We herein report a rare case of ileal adenocarcinoma that was completely removed
      by endoscopic submucosal dissection (ESD) without any complications. An 80-year
      old man was referred to our hospital to undergo treatment for an ileal tumor.
      Conventional colonoscopy showed a reddish depressed lesion that was classified as
      type 0-IIc according to the Paris classification. The ileal tumor was
      successfully removed en bloc by ESD with a negative surgical margin. The
      histological findings showed a well-differentiated adenocarcinoma with no
      submucosal or lymphovascular invasion. Colonoscopy and CT performed one year
      after ESD showed no local recurrence, stenosis, or lymph node metastasis.

PMID- 28502929
TI  - Multifocal Colonic Wall Abscesses during Anti-Tumor Necrosis Factor (TNF)-alpha
      Therapy for a Patient with Ulcerative Colitis: A Very Rare Manifestation of
      Infectious Complications.
AB  - A 24-year-old woman was transferred to our hospital under suspicion of an
      exacerbation of her known ulcerative colitis. Colonoscopy revealed an edematous
      swelling and multifocal discharge of pus throughout the descending colon,
      concurrent with active ulcerative colitis findings in the rectum and sigmoid
      colon. Computed tomography showed a thickened wall and multifocal abscesses
      within the wall of the descending colon. Two weeks after starting antimicrobial
      therapy, she was discharged home. This is the first case report of multifocal
      colonic wall abscesses. In order not to increase the risk of serious infection
      associated with anti-TNF-alpha therapy, proper qualification and strict
      monitoring are essential.

PMID- 28502930
TI  - Branch Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas Involving
      Type 1 Localized Autoimmune Pancreatitis with Normal Serum IgG4 Levels
      Successfully Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration and
      Treated without Pancreatic Surgery.
AB  - We herein report a 68-year-old man with branch duct intraductal papillary
      mucinous neoplasms of the pancreas (BD-IPMNs) involving type 1 localized
      autoimmune pancreatitis (AIP) with normal serum IgG4 levels. Although he was
      referred to our medical center due to suspicion of pancreatic cancer concomitant
      with BD-IPMNs, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)
      revealed a mass suspected of being pancreatic cancer to be type 1 AIP. Steroid
      administration notably reduced the mass. Although the clinical diagnosis of
      pancreatic masses in patients with IPMN can be occasionally challenging,
      performing a pathological examination by EUS-FNA may prevent unnecessary
      pancreatic surgery in cases of possible AIP.

PMID- 28502932
TI  - Rhabdomyolysis after High Intensity Resistance Training.
AB  - Rhabdomyolysis, which is a characteristic occurrence in associated with muscle
      cell necrosis, develops due to various causes. We herein report a rare case of a
      patient with rhabdomyolysis after high intensity resistance training, in which
      markedly elevated levels of serum creatine kinase (CK) and urine myoglobin were
      observed. A previously healthy 37-year-old man presented with severe myalgia and
      dark urine after performing high-intensity exercise. The patient's serum CK level
      was 95,100 U/L and his urine myoglobin level was 160,000 ng/mL. His symptoms and
      laboratory findings gradually improved with the intravenous administration of
      saline and no complications (including electrolyte imbalance and acute renal
      failure) developed.

PMID- 28502931
TI  - Graves' Disease in Pediatric and Elderly Patients with 22q11.2 Deletion Syndrome.
AB  - 22q11.2 Deletion Syndrome (22qDS) is often complicated by autoimmune diseases. To
      clarify the causal relationship, we examined the lymphocyte subset distribution
      and the human leucocyte antigen (HLA) in two female patients (one child and an
      elderly) with Graves' disease (GD) and 22qDS. Thymus dysgenesis might have
      contributed to the T-cell imbalance and the lack of negative selection in both
      cases. Notably, HLA-DR14, a known risk factor for GD in Japanese individuals and
      the decreased regulatory T-cell numbers that were seen in the pediatric case, may
      affect the early onset of GD. Central and peripheral tolerance and Th1 cells
      appeared to be associated with the pathogenesis of GD in 22qDS.

PMID- 28502934
TI  - A Cryptogenic Case of Fulminant Fibrosing Organizing Pneumonia.
AB  - Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids
      with a favorable outcome. Rare cases of organizing pneumonia are rapidly
      progressive. Yousem et al. studied pathologic predictors of idiopathic
      bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis.
      Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74
      year-old female non-smoker presented with a 2-week history of dry cough followed
      by dyspnea and a fever. The clinical course was fulminant, but we successfully
      performed bronchoscopy. After the diagnosis of FOP, we treated the patient with
      mechanical ventilation and high-doses of steroids/immunosuppressants, which
      improved the disease.

PMID- 28502933
TI  - Sustained Tubulointerstitial Inflammation in Kidney with Severe Leptospirosis.
AB  - Leptospirosis is frequently associated with acute kidney injury. Some survivors
      are known to progress to chronic kidney disease due to sustained
      tubulointerstitial inflammation. We present a case of severe leptospirosis with
      acute renal failure. Although antibiotic therapy resolved the infection, moderate
      renal dysfunction remained. A renal biopsy demonstrated marked inflammatory
      infiltration in the tubules and interstitium. Many of the inflammatory cells were
      CD68-positive monocytes/macrophages, predominantly M1 phenotype. An intermediate
      dose of oral corticosteroids normalized the patient's serum creatinine levels. We
      suggest that corticosteroid therapy may be a therapeutic option for some patients
      with sustained tubulointerstitial nephritis who survive severe leptospirosis.

PMID- 28502935
TI  - Two Cases of Neurolymphomatosis with Fatal Bilateral Vocal Cord Paralysis that
      were Diagnosed with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG
      PET)/CT.
AB  - Neurolymphomatosis is a rare entity defined as nerve infiltration by neurotropic
      abnormal lymphocytes which can lead to the development of neuropathy, with
      typical presentations including pain, hypoesthesia, paresthesis and palsy. We
      herein report two cases where critical bilateral vocal cord paralysis due to
      neurolymphomatosis in recurrent nerves occurred in refractory Burkitt lymphoma
      and adult T-cell lymphoma patients. High-dose methotrexate and intrathecal
      chemotherapy injection for the nervous lesions were ineffective, and the patients
      died. Neurolymphomatosis of the recurrent nerve is an emergent and difficult
      complication and should be suspected when sudden onset of aphasia, hoarseness or
      shortness of breath is found in refractory lymphoma patients.

PMID- 28502936
TI  - Successful Treatment of Behcet's Disease Associated with Acute Myeloid Leukemia
      with Myelodysplasia-related Changes Using Azacitidine and Tacrolimus before
      Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - The coexistence of acute myeloid leukemia (AML) with Behcet's disease (BD) is
      rare. The optimum treatment for AML-associated BD has not been established. We
      herein report a patient with BD who developed AML with myelodysplasia-related
      changes. Induction chemotherapy caused complete remission of the AML but worsened
      the BD. Thereafter, AML was treated with azacitidine. The BD was steroid
      dependent. Tacrolimus was added, which improved the BD. The patient underwent
      allogeneic hematopoietic stem cell transplantation (HSCT) and remains in complete
      remission for both diseases. Allogeneic HSCT was found to be a potent therapeutic
      option for AML-associated BD. In addition, azacitidine and tacrolimus were shown
      to be a suitable bridging regimen before HSCT.

PMID- 28502937
TI  - Acquired Inhibitors to Multiple Coagulation Factors (V, IX, and XII) Identified
      in a Unique Patient with Hepatocellular Carcinoma.
AB  - An acquired formation of inhibitors to coagulation factors is a rare type of
      coagulopathy. The development of inhibitors for multiple coagulation factors has
      never been reported. A 75-year-old Japanese female underwent interventional
      therapy for hepatocellular carcinoma. Five days after the last intervention, her
      prothrombin time decreased to 10%, and her activated partial thromboplastin time
      (APTT) lengthened to 265.1 sec. The activities for coagulation factors showed
      significantly reduced activities (<10%) of factors V, IX, and XII. A cross-mixing
      test demonstrated an inhibitor pattern, and inhibitory antibodies against factors
      V, IX, and XII were detected. We discuss our patient's etiology and pathogenesis.

PMID- 28502938
TI  - Successful Treatment of Catastrophic Antiphospholipid Antibody Syndrome
      Associated with MALT Lymphoma by Autologous Hematopoietic Stem Cell
      Transplantation.
AB  - A 37-year-old woman with extranodal marginal-zone lymphoma was admitted with a
      fever, hemiplegia, and severe dyspnea after chemotherapy. Catastrophic
      antiphospholipid antibody syndrome (CAPS) was suspected based on the
      histopathological confirmation of small-pulmonary vessel occlusion, evidence of
      the involvement of three organs, and elevated lupus anticoagulant assay results
      in a short time span. The patient responded to the initial treatment. One month
      later, the CAPS and lymphoma relapsed, and the patient underwent autologous
      hematopoietic stem cell transplantation. Complete remission of the lymphoma has
      been successfully maintained, and the condition of the patient has remained
      stable for two years with no further evidence of thrombosis.

PMID- 28502939
TI  - Myelodysplastic Syndrome Developing Presacral Extramedullary Hematopoiesis with
      Atypical MRI Findings.
AB  - A 64-year-old woman was diagnosed to have refractory cytopenia with multilineage
      dysplasia (RCMD) including an increased number of sideroblasts in the bone marrow
      (BM). Computed tomography (CT) revealed a presacral mass which showed iso- or
      high-intensity signals according to T1-weighted and hypo-intensity signals on T2
      weighted magnetic resonance imaging (MRI). CT-guided biopsy revealed the presence
      of hematopoietic tissue with features that correlated with the BM findings. While
      the formation of extramedullary hematopoiesis in the presacral area is rare, it
      is important to differentiate it from other parasacral tumors even though such
      differentiation is often difficult. This patient demonstrated atypical MRI
      signals possibly due to an increase in the cellular iron content of the erythroid
      precursors.

PMID- 28502940
TI  - PET Imaging of 18F-FDG, 11C-methionine, 11C-flumazenil, and 11C-4DST in
      Progressive Multifocal Leukoencephalopathy.
AB  - The use of positron emission tomography (PET) imaging in progressive multifocal
      leukoencephalopathy (PML) has rarely been reported. We herein report a set of PET
      images in a 63-year-old patient with PML. In PML lesions, the uptake of 18F
      fluorodeoxyglucose, 11C-methionine, 11C-flumazenil, and [methyl-11C]4'
      thiothymidine was decreased, increased, decreased, and unchanged, respectively.
      These results suggest that glucose metabolism decreased, protein synthesis
      increased, neuronal integrity decreased, and the DNA synthesis and cellular
      proliferation of host cells were not activated in PML lesions. These results may
      reflect very little infiltration by inflammatory cells and active infection with
      JC virus in this case.

PMID- 28502941
TI  - The Sequential Ultrasonographic, Electrophysiological and MRI Findings in a
      Patient with the Pharyngeal-cervical-brachial Variant of Guillain-Barre Syndrome
      from the Acute Phase to the Chronic Phase.
AB  - Acute progressive weakness in bulbar, neck and limbs is included in several
      differential diagnoses, including the pharyngeal-cervical-brachial (PCB) variant
      of Guillain-Barre syndrome (GBS). Patients with the PCB variant of GBS are
      reported to have localized diagnostic cervical spinal nerve abnormalities that
      can be examined by nerve ultrasonography (NUS) and magnetic resonance neurography
      (MRN). We herein report the case of a 77-year-old man with the PCB variant of
      GBS. Although the nerve conduction study (NCS) findings were indirect indicators
      for an early diagnosis, the combination of NCS and NUS was a useful complementary
      measure that facilitated an early diagnosis. MRN did not show any apparent
      diagnostic abnormalities. After early treatment, the patient was discharged and
      returned home.

PMID- 28502943
TI  - The Development of Cerebral Venous Thrombosis after Tadalafil Ingestion in a
      Patient with Antiphospholipid Syndrome.
AB  - We report a case of cerebral venous thrombosis related to the ingestion of
      tadalafil. A 45-year-old man presented with posterior headache and was diagnosed
      with tension headache. Five days later, he was transported to our hospital via
      ambulance due to a tonic-clonic seizure. Head MRI showed cerebral venous
      thrombosis (CVT). He confessed to having recently taken a large doses of
      tadalafil. His anti-cardiolipin antibody and anti-caldiolipin-beta2-glycoprotein
      I complex antibody levels were elevated. Our case suggests the possibility that
      tadalafil is related to both cardiovascular complications and CVT in patients
      with hypercoagulability. Patients with conditions associated with
      hypercoagulability, including antiphospholipid syndrome may be better advised to
      avoid the use of tadalafil.

PMID- 28502944
TI  - Reactive Arthritis Caused by Yersinia enterocolitica Enteritis.
AB  - We report a case of reactive arthritis (ReA) triggered by Yersinia enterocolitica
      enteritis. A 24-year-old Japanese man developed polyarthritis in the lower limbs.
      Two weeks prior to these symptoms, he noted diarrhea, right lower abdominal pain
      and a fever. Y. enterocolitica was not isolated from a stool culture; however, he
      was diagnosed with ReA based on the colonoscopic findings of a high anti-Y.
      enterocolitica antibody titer and HLA-B27 antigen positivity. Following treatment
      with methotrexate and steroids, his arthritis improved. This is the first
      reported Japanese case of ReA in the English literature after a gastrointestinal
      infection caused by Y. enterocolitica.

PMID- 28502942
TI  - Brain Biopsy Is More Reliable than the DNA test for JC Virus in Cerebrospinal
      Fluid for the Diagnosis of Progressive Multifocal Leukoencephalopathy.
AB  - The current standard diagnostic approach for progressive multifocal
      leukoencephalopathy (PML) is to perform a DNA test to identify the presence of
      the JC virus in cerebrospinal fluid (CSF). A 32-year-old woman with a 5-year
      history of systemic lupus erythematosus developed right hemiplegia and motor
      aphasia. MRI revealed a large white matter lesion in the left frontal lobe. JC
      virus DNA was undetectable in the CSF, but a brain biopsy showed typical
      histopathology and a high DNA load of the JC virus. The patient was treated with
      mefloquine and mirtazapine, and is currently alive at 24 months after onset. An
      early brain biopsy may therefore be important for making a timely diagnosis of
      PML.

PMID- 28502945
TI  - Sporotrichal Tenosynovitis Diagnosed Helpfully by Musculoskeletal
      Ultrasonography.
AB  - A 72-year-old man presented with persistent oligoarthritis and positive results
      for rheumatoid factor and was suspected of having rheumatoid arthritis (RA).
      However, the musculoskeletal ultrasonography (MSUS) findings were not consistent
      with those of typical RA. He had undergone surgery for carpal tunnel syndrome,
      which allowed both histopathological and microbiological examinations to be
      performed. A synovial tissue culture was positive for Sporothrix schenckii, and
      he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal
      therapy, and the sporotrichal tenosynovitis resolved. This case suggests that
      MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be
      considered in the differential diagnosis of RA.

PMID- 28502946
TI  - Two Cases of Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure,
      and Organomegaly (TAFRO) Syndrome with High Serum Procalcitonin Levels, Including
      the First Case Complicated with Adrenal Hemorrhaging.
AB  - Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal failure, and
      Organomegaly (TAFRO) syndrome is a recently described systemic inflammatory
      disorder characterized by thrombocytopenia, anasarca, fever, reticulin
      fibrosis/renal failure, and organomegaly. It has an acute or subacute onset of
      unknown etiology, although some pathological features resemble those of
      multicentric Castleman disease. We here report two cases of TAFRO syndrome. The
      symptoms and pathological findings in these cases met the 2015 diagnostic
      criteria. Our cases showed high serum procalcitonin levels, suggesting bacterial
      infection as an onset trigger. In addition, Case 1 is the first case complicated
      with adrenal hemorrhaging. Case 2 is the second case of tocilizumab-resistant
      TAFRO syndrome successfully treated with rituximab.

PMID- 28502949
TI  - Pulmonary Cryptococcosis Complicated by Sarcoidosis.

PMID- 28502948
TI  - Disseminated Cryptococcosis with Adrenal Insufficiency and Meningitis in an
      Immunocompetent Individual.
AB  - We present a case of cryptococcosis with adrenal insufficiency and meningitis in
      a healthy host without any risk factors. Antifungal therapy did not reduce the
      cryptococcal antigen titers of the cerebrospinal fluid and serum or the bilateral
      adrenal gland enlargement. It was suggested that the adrenal glands were the
      focus of persistent fungemia. Removal of both adrenal glands brought about a
      response to antifungal therapy. We conclude that if antifungal therapy is
      ineffective, bilateral adrenalectomy is an effective measure for treatment of
      such patients. Cryptococcosis is a possible cause of primary adrenal
      insufficiency in immunocompetent patients.

PMID- 28502947
TI  - Intractable Cutaneous Nontuberculous Mycobacteriosis (Mycobacterium abscessus)
      during Treatment for Systemic Lupus Erythematosus.
AB  - Mycobacterium abscessus infection tends to occur in patients with an advanced
      immunocompromised status. We encountered a case of intractable cutaneous M.
      abscessus infection that developed in a patient with systemic lupus erythematosus
      (SLE) during maintenance therapy. A 28-year-old woman developed a fever and
      redness of the skin on her buttocks. General antibacterial therapy was
      ineffective, and acid-fast bacteria were detected in the biopsy that was
      conducted to differentiate the dermal symptoms of SLE. The clinical findings
      eventually improved; however, the symptoms recurred multiple times during
      treatment. Despite recent advances in SLE treatment, M. abscessus infection
      remains a considerable complication of SLE.

PMID- 28502950
TI  - Colitis Associated with Nintedanib Therapy for Idiopathic Pulmonary Fibrosis
      (IPF).

PMID- 28502951
TI  - Diffuse Large B-cell Lymphoma Involving the Skeletal Muscle.

PMID- 28502952
TI  - Lemierre's Syndrome Variant with External Jugular Vein Thrombosis.

PMID- 28502953
TI  - Immune Reconstitution Syndrome in a Patient with AIDS.

PMID- 28502955
TI  - Blue light inhibits the enlargement of Erythrobacter litoralis spheroplasts.

PMID- 28502954
TI  - Acute Prevertebral Calcific Tendinitis.

PMID- 28502956
TI  - Evaluation of biofilm-forming ability of bacterial strains isolated from the roof
      of an old house.
AB  - The bacterial diversity associated with biofilm-forming ability was studied.
      Eighteen bacterial strains were isolated from a microbial film collected from the
      roof of an old house located in Sfax, Tunisia. The purity of these microorganisms
      was confirmed by microscopic observation after repeated streaking on a Tryptic
      Soy agar medium. Biofilm formation was estimated using preliminary tests
      including a motility test, microbial adhesion to solvents (MATS), and the Congo
      Red Agar method (CRA). Since these tests showed no significant result, microplate
      tests, such as crystal violet and resazurin assays, were used. The results
      obtained showed that strain S61 was able to form a biofilm within 24 h (OD570 =
      4.87). The viability of the S61 biofilm with resazurin assessed with fluorescence
      measurement was about 1.5 * 103. The S61 strain was identified as Staphylococcus
      epidermidis. In the biofilm studied here, it was the most biofilm-forming
      bacterium and will be used as a bacterial model for studying anti-biofilm
      activity.

PMID- 28502957
TI  - 1-Methoxypyrrole-2-carboxamide-A new pyrrole compound isolated from Streptomyces
      griseocarneus SWW368.
AB  - A new pyrrole compound, 1-methoxypyrrole-2-carboxamide, was obtained from a
      culture broth of Streptomyces griseocarneus SWW368, which was isolated from the
      rhizospheric soil under a Para rubber tree (Hevea brasiliensis). The chemical
      structure was elucidated by 1D NMR, 2D NMR, and MS, as a pyrrole ring with a N
      methoxy group and a primary amide group. It exhibited antibacterial properties
      against Kocuria rhizophila, Staphylococcus aureus and Xanthomonas campestris pv.
      oryzae; however, cytotoxicity of the compound at 714 MUM against several
      mammalian tumor cell lines, i.e. A549, PANC1, HT29, HT1299 and HeLa S3, were not
      detected.

PMID- 28502958
TI  - A Complicated Case of Pregnancy Involving a Presacral Epidermoid Cyst.
AB  - Although presacral developmental cysts, including epidermoid cysts, are
      relatively rare diseases, an intrapelvic mass found for the first time in early
      pregnancy should be followed-up with the possibility of presacral developmental
      cysts in mind to be alert to the signs of local infection and malignancy. We
      treated a pregnant patient with presacral cystic disease. During pregnancy,
      percutaneous fenestration was performed because the cyst caused severe
      compression symptoms and complicated bacterial infection. Laparoscopic total cyst
      excision was performed after cesarean section. There is no suggested criterion to
      make a decision for the delivery mode. The mass should be removed completely to
      reduce the risk of recurrence and malignant progression.

PMID- 28502959
TI  - Squamous Cell Carcinomas on Bilateral Feet Arising in Long-Standing Eczematous
      Lesions.
AB  - We present a woman with squamous cell carcinomas on both feet in long-standing
      eczematous lesions. Histopathological examination of biopsies from the both feet
      revealed highly atypical cells invading the reticular layer of the dermis in the
      hyperkeratotic lesion and they were associated with surrounding dermatitis with
      spongiosis. Although the cause and etiology of eczema in our case is unclear, we
      speculate that the exceptionally long-lasting dermatitis might have induced
      double SCCs on bilateral feet with an unusual constitution. To the best of our
      knowledge, this is a first case of SCC on bilateral feet arising in long-standing
      eczematous lesions.

PMID- 28502960
TI  - Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis
      and Disease Subsetting.
AB  - The presence of circulating anti-nuclear antibodies (ANAs) is a hallmark of
      immune dysregulation in patients with systemic sclerosis (SSc). Currently, a
      variety of SSc-specific ANAs, including anticentromere, anti-topoisomerase I, and
      anti-RNA polymerase III antibodies, have been well characterized, and their
      commercial kits are available worldwide. Since these autoantibodies are
      specifically detected in SSc patients and are associated with unique sets of
      disease manifestations, they are widely used in routine clinical practice for
      diagnosis, clinical subgrouping, and prediction of future organ involvements and
      prognosis. In addition, SSc-specific ANAs are also useful in predicting future
      development of SSc in patients with Raynaud's phenomenon without any scleroderma
      skin changes, because their production often precedes onset of SSc symptoms.
      Application of circulating SSc-specific ANA measurement to clinical practice has
      greatly improved patient care, but utility of the autoantibody testing could be
      maximized by combining other clinical information, such as degree and extent of
      skin thickness and disease duration.

PMID- 28502962
TI  - Treatment Results of Transurethral Resection of the Prostate by Non-Japanese
      Board-Certified Urologists for Benign Prostate Hyperplasia: Analysis by Resection
      Volume.
AB  - INTRODUCTION: Transurethral resection of the prostate (TURP) is the gold standard
      for surgical treatment of benign prostatic hyperplasia (BPH), but it has
      complications such as bleeding and transurethral resection syndrome. The
      treatment results of TURP performed by non-Japanese board-certified urologists
      were examined, and the results were analyzed according to the resection volume to
      determine how much resection volume was suitable for non-Japanese board-certified
      urologists. MATERIALS AND METHODS: A total of 72 cases that underwent TURP for
      BPH at our hospital were examined. The patients were divided into three groups by
      resection volume (<20 g, 20-30 g, >30 g). The operators were five non-Japanese
      board-certified urologists. Various clinical factors were examined among the
      three groups before and after TURP. RESULTS: The average operation time and
      resection volume were significantly different among the groups. There were more
      transfused cases with greater resection volume. The changes from before to after
      TURP in the International Prostate Symptom Score, total prostate volume, and
      maximum flow rate were significantly different among the three groups, but the
      rates of these changes were not. CONCLUSIONS: In this study, TURP performed by
      non-Japanese board-certified urologists was relatively safe and achieved
      sufficient efficacy. Cases with resection volume less than 20 g appear the most
      appropriate for non-Japanese board-certified urologists.

PMID- 28502961
TI  - Haptoglobin Reduces Inflammatory Cytokine INF-gamma and Facilitates Clot
      Formation in Acute Severe Burn Rat Model.
AB  - Haptoglobin exerts renal protective function by scavenging free hemoglobin from
      the urine and blood stream in patients with hemolytic disorders. Recent studies
      elucidate the relationships between haptoglobin and inflammation. In addition,
      coagulopathy is often induced by systemic inflammation characterized by the
      presence of vascular endothelial damage. We hypothesize that haptoglobin might
      have an anti-inflammatory effect and affect hypercoagulability using rat burn
      model. Thirty anesthetized rats of six-weeks of age received over 30% full
      thickness scald burn on the dorsal skin surface. All rats were injected with
      either haptoglobin (Hpt) or normal saline (NS) intraperitoneally. The rats were
      divided into three groups: 1) control group (NS 20 mL/kg); 2) low concentration
      of Hpt group, L-Hpt, (Hpt 4 mL (80 U) /kg+NS 16 mL/kg); and 3) high concentration
      of Hpt group, H-Hpt, (Hpt 20 mL (400 U) /kg). While under anesthesia, all rats
      were euthanized by exsanguination at 6 hours (N=5) and 24 hours (N=5).
      Inflammatory and anti-inflammatory cytokines were measured and whole-blood
      viscoelastic tests were performed by thromboelastometry (ROTEM). Haptoglobin
      significantly reduced free hemoglobin 24 hours after the injury. Improvement of
      hematuria was confirmed in the H-Hpt group. There were no differences in thrombin
      antithrombin complex and plasmin-alpha2 plasmin inhibitor complex. The
      haptoglobin tended to decrease interferon-gamma (IFN-gamma) in H-Hpt group. ROTEM
      findings of the L-Hpt group showed significantly higher clot firmness and shorter
      time to maximum clot formation velocity than the control group. Haptoglobin
      reduced INF-gamma, and accelerated speed of clot formation in acute phase of
      severe burn.

PMID- 28502963
TI  - A Case of Syringocystadenoma Papilliferum with Tubular Papillary Adenoma of the
      Chest.
AB  - We report a case of syringocystadenoma papilliferum (SCAP) combined with tubular
      papillary adenoma (TPA) arising on the chest of a 45-year-old Japanese woman.
      Histopathological examination revealed the characteristic findings of SCAP in the
      superficial part of the lesion and those of TPA in the deeper part. We reviewed
      the English literature about this combination. SCAP and TPA have the same
      cellular components, but show differences of the general structure. The
      combination of these two neoplasms is more frequent than expected by most
      dermatopathologists or pathologists. This combination is frequently seen in
      patients with nevus sebaceus (NS), but it is also found in patients without NS.

PMID- 28502964
TI  - Primary Volvulus of the Small Intestine Exhibiting Chylous Ascites: A Case
      Report.
AB  - BACKGROUND: Primary volvulus of the small intestine associated with chylous
      ascites is very rare, with only four reported cases. In this paper, we report a
      new case of primary volvulus associated with chylous ascites. CASE PRESENTATION:
      The patient was a 70-year-old man. After experiencing bloating and abdominal pain
      for several hours, he called an ambulance and underwent an emergency examination
      at our hospital. Abdominal distension, pressure pain, and rebound tenderness were
      observed throughout his entire abdomen. The patient had a history of hypertension
      for which he was receiving oral treatment. Abdominal contrast-enhanced computed
      tomography (CT) revealed an edematous change in the intestinal membrane and
      volvulus of the small intestine. As findings suggestive of ischemia were observed
      in part of the intestines, emergency surgery was performed on the day of
      admission. Open surgery revealed approximately 500 mL of chylous ascites in the
      abdominal cavity. The small intestine had twisted 180 degrees  in a counter
      clockwise direction at the root of the superior mesenteric artery, and the
      mesentery appeared milky white with edematous changes extending 75 to 240 cm from
      the ligament of Treitz. There was no evidence of intestinal necrosis; therefore
      intestinal resection was not performed. The volvulus of the small intestine was
      corrected. Moreover, because there was no other underlying disease observed,
      surgery was completed. The ascites collected during surgery revealed high levels
      of triglycerides at 332 mg/dL, and chylous ascites was diagnosed. An abdominal CT
      performed on the third day after surgery showed an improvement in intestinal
      edema, and primary volvulus of the small intestine associated with chylous
      ascites was diagnosed. Postoperative progress was good, and the patient was
      discharged on hospital day 10.

PMID- 28502965
TI  - Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular
      Opacity: Report of a Case.
AB  - Herein, we describe our experience in treating a case of primary pulmonary mucosa
      associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old
      man was referred to our hospital. Computed tomography showed a nodular opacity
      measuring 20 mm in diameter with regular margins in segment 5 of the right middle
      lobe of the lung. Although the bronchoscopic brush cytology result was class III,
      the patient was tentatively diagnosed with suspected mucosa-associated lymphoid
      tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The
      pathological findings showed nodular proliferation of small to medium-sized,
      mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague
      follicles suggesting follicular colonization in some areas. The patient was
      diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid
      tissue lymphoma. He has remained well to date, 23 months after surgery, without
      evidence of recurrence.

PMID- 28502966
TI  - Laparoscopic Repair of Vaginal Evisceration after Abdominal Hysterectomy for
      Uterine Corpus Cancer: A Case Report and Literature Review.
AB  - Vaginal cuff dehiscence is a rare but serious complication that can develop after
      hysterectomy. Emergent surgical intervention is required for vaginal cuff
      dehiscence due to the potential subsequent vaginal evisceration, which may lead
      to necrosis of the small bowel. A 62-year-old nulliparous woman with a 30-year
      history of smoking, diabetes mellitus, and rheumatoid arthritis (treated with
      oral steroids) presented with a vaginal cuff dehiscence. Thirty-eight days before
      the admission, she had undergone a radical operation including total abdominal
      hysterectomy for uterine corpus cancer at another hospital. We performed emergent
      laparoscopic surgery to reduce the prolapsed small bowel into the abdominal
      cavity and repaired the vaginal cuff with a two-layer continuous closure using
      absorbable barbed sutures. The patient experienced no postoperative
      complications, and no recurrence of the vaginal cuff dehiscence occurred. Vaginal
      cuff dehiscence and evisceration can be surgically managed using an abdominal,
      vaginal, or laparoscopic approach, and the choice of method should be based on
      patient characteristics and the surgeon's skills. Laparoscopic vaginal cuff
      repair with a two-layer continuous closure using absorbable barbed sutures is a
      minimally invasive technique that is safe and effective for medically stable
      patients with no small bowel injury or vascular compromise and no pelvic abscess.

PMID- 28502967
TI  - Neck and Occipital Pain Caused by Deep Cervical Intramuscular Lipoma: A Surgical
      Case.
AB  - A lipoma is a slow-growing, benign tumor and is usually asymptomatic; hence,
      surgical intervention can often be avoided in patients with these tumors in the
      cervical and cranial area. Lipomas arise most commonly in the subcutaneous fat,
      but occasionally in muscle tissue. Intramuscular lipomas in the cervico-cranial
      area have rarely been reported. We describe here a patient with a large
      intramuscular lipoma in the deep cervical tissue. The patient experienced
      troublesome pain in the neck and occipital area, and surgical treatment was
      therefore suggested. Particularly in the cervical area, intramuscular lipomas
      sometimes invade the surrounding muscles and tissue layers and develop into an
      irregular mass, despite being benign. In addition, the cervical area has one of
      the most complex muscle structures. Nevertheless, surgical management of
      intramuscular lipoma in the cervical and cranial area is sometimes indicated, for
      example, in patients with clinical symptoms or masses with a tendency to grow
      large.

PMID- 28502968
TI  - Prokaryotic Communities at Different Depths between Soils with and without Tomato
      Bacterial Wilt but Pathogen-Present in a Single Greenhouse.
AB  - The characterization of microbial communities that promote or suppress soil-borne
      pathogens is important for controlling plant diseases. We compared prokaryotic
      communities in soil with or without the signs of tomato bacterial wilt caused by
      Ralstonia solanacearum. Soil samples were collected from a greenhouse at two
      different depths because this pathogen is present in deep soil. We used samples
      from sites in which we detected phcA, a key gene regulating R. solanacearum
      pathogenicity. The pyrosequencing of prokaryotic 16S rRNA sequences in four soil
      samples without disease symptoms but with phcA and in two soil samples with
      disease symptoms indicated that community richness was not significantly
      different between these two soils; however, microbial diversity in the lower soil
      layer was higher in soil samples without disease symptoms but with phcA. A
      difference in prokaryotic community structures between soil samples with and
      without bacterial wilt was only observed in the upper soil layer despite apparent
      similarities in the communities at the phylum level. Proteobacteria,
      Acidobacteria, Chloroflexi, Verrucomicrobia, and several Archaea were more
      abundant in soil samples without disease symptoms, whereas taxa in another eight
      phyla were more abundant in soil samples with disease symptoms. Furthermore, some
      prokaryotic taxa were abundant specifically in the lower layer of soil,
      regardless of whether disease was present. These prokaryotic taxa may suppress or
      accelerate the pathogenesis of bacterial wilt and are good targets for future
      studies on disease control.

PMID- 28502969
TI  - Transcription of [FeFe]-Hydrogenase Genes during H2 Production in Clostridium and
      Desulfovibrio spp. Isolated from a Paddy Field Soil.
AB  - Changes in the relative abundances of the transcripts of hydA gene paralogs for
      [FeFe]-hydrogenase in Clostridium sp. strain H2 and Desulfovibrio sp. strain A1
      isolated from paddy field soil were analyzed during H2 production. Strains H2 and
      A1 had at least five and two phylogenetically different hydA genes, respectively.
      The relative abundances of their hydA transcripts differed among the paralogs and
      H2 production activity changed in a manner that depended on the growth phase and
      conditions. Increases or decreases in the relative abundances of the transcripts
      of two out of five hydA genes in strain H2 correlated with changes in H2
      production rates, whereas those of the others remained unchanged or decreased. In
      strain A1, the relative abundances of the transcripts of two hydA genes differed
      between monoculture, sulfate-reducing, and syntrophic, methanogenic conditions.
      The relative abundance of the transcripts of one hydA gene, predicted to encode a
      cytosolic [FeFe]-hydrogenase, was higher under syntrophic, methanogenic
      conditions than sulfate-reducing conditions, while that of the transcripts of the
      other hydA gene decreased with time under both conditions. This study showed that
      the transcription of the hydA gene during growth with active H2 production was
      differently regulated among the paralogs in H2 producers isolated from paddy
      field soil.

PMID- 28502970
TI  - Is Regular Screening for Intracranial Aneurysm Necessary in Patients with
      Autosomal Dominant Polycystic Kidney Disease? A Systematic Review and Meta
      analysis.
AB  - BACKGROUND: The prevalence of intracranial aneurysm in patients with autosomal
      dominant polycystic kidney disease (ADPKD) is higher than that among the general
      population. We performed a systematic review and meta-analysis on the prevalence
      and natural history of intracranial aneurysm among patients with ADPKD. METHODS:
      Medline, Embase, Web of Science and Scopus, from inception to July 2016, were
      searched for studies reporting the occurrence of intracranial aneurysms among
      participants with ADPKD. Two authors independently assessed the eligibility of
      all retrieved studies and extracted data. Information on the prevalence of
      intracranial aneurysms and their natural history in participants with ADPKD was
      collected from all included studies. RESULTS: Fifteen studies with 1,490
      participants with ADPKD were pooled to study about the prevalence of intracranial
      aneurysm in participants with ADPKD, and the prevalence rate was found to be 10%
      (95% CI 7-13%). Studies from China, Japan and Europe (Germany, Poland) reported a
      higher prevalence of intracranial aneurysm. Having a family history of
      haemorrhagic stroke or intracranial aneurysm was a risk factor for aneurysm
      occurrence. Twenty-three percent (95% CI 15-31%) of the participants had multiple
      aneurysms. Most of the aneurysms were small (<6 mm) and located in the anterior
      circulation. Five studies with 171 participants (83 with 106 aneurysms at
      baseline and 88 without) were analyzed to understand the natural history of
      aneurysms, with an incidence of aneurysm growth, new aneurysm and aneurysm
      rupture of 1.84% (followed up for 435 person-years), 0.57% (1,227 person-years)
      and 0.13% (792 person-years) respectively. CONCLUSIONS: Screening for
      intracranial aneurysm is recommended in patients with ADPKD when there is a
      family history of haemorrhagic stroke or intracranial aneurysm and when they are
      from China, Japan or Europe (Germany, Poland). Based on existing data, regular
      imaging follow-up is not supported. High-quality, prospective studies are needed
      in the future.

PMID- 28502971
TI  - Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression.
AB  - BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical
      transcription factor for the antioxidative stress response and it activates a
      variety of cytoprotective genes related to redox and detoxification. NRF2
      activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH
      associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through
      ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a
      major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2
      system has been proposed to be a therapeutic target for renal protection.
      SUMMARY: Oxidative-stress molecules, such as reactive oxygen species, accumulate
      in the kidneys of animal models for acute kidney injury (AKI), in which NRF2 is
      transiently and slightly activated. Genetic or pharmacological enhancement of
      NRF2 activity in the renal tubules significantly ameliorates damage related to
      AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing
      oxidative stress. These beneficial effects of NRF2 activation highlight the KEAP1
      NRF2 system as an important target for kidney disease treatment. However, a phase
      3 clinical trial of a KEAP1 inhibitor for patients with stage 4 CKD and type-2
      diabetes mellitus (T2DM) was terminated due to the occurrence of cardiovascular
      events. Because recent basic studies have accumulated positive effects of KEAP1
      inhibitors in moderate stages of CKD, phase-2 trials have been restarted. The
      data from the ongoing projects demonstrate that a KEAP1 inhibitor improves the
      glomerular filtration rate in patients with stage 3 CKD and T2DM without safety
      concerns. Key Message: The KEAP1-NRF2 system is one of the most promising
      therapeutic targets for kidney disease, and KEAP1 inhibitors could be part of
      critical therapies for kidney disease.

PMID- 28502972
TI  - Distribution, Innervation, and Cellular Organization of Taste Buds in the Sea
      Catfish, Plotosus japonicus.
AB  - The gustatory system of the sea catfish Plotosus japonicus, like that of other
      catfishes, is highly developed. To clarify the details of the morphology of the
      peripheral gustatory system of Plotosus, we used whole-mount immunohistochemistry
      to investigate the distribution and innervation of the taste buds within multiple
      organs including the barbels, oropharyngeal cavity, fins (pectoral, dorsal, and
      caudal), and trunk. Labeled taste buds could be observed in all the organs
      examined. The density of the taste buds was higher along the leading edges of the
      barbels and fins; this likely increases the chance of detecting food. In all the
      fins, the taste buds were distributed in linear arrays parallel to the fin rays.
      Labeling of nerve fibers by anti-acetylated tubulin antibody showed that the
      taste buds within each sensory field are innervated in different ways. In the
      barbels, large nerve bundles run along the length of the organ, with fascicles
      branching off to innervate polygonally organized groups of taste buds. In the
      fins, nerve bundles run along the axis of fin rays to innervate taste buds lying
      in a line. In each case, small fascicles of fibers branch from large bundles and
      terminate within the basal portions of the taste buds. Serotonin
      immunohistochemistry demonstrated that most of the taste buds in all the organs
      examined contained disk-shaped serotonin-immunopositive cells in their basal
      region. This indicates a similar organization of the taste buds, in terms of the
      existence of serotonin-immunopositive basal cells, across the different sensory
      fields in this species.

PMID- 28502973
TI  - The job competency of radiological technologists in Korea based on specialists
      opinion and questionnaire survey.
AB  - PURPOSE: Although there are over 40,000 licensed radiological technologists (RTs)
      in Korea, job competency standards have yet to be defined. This study aims to
      clarify the job competency of Korean RTs. METHODS: A task force team of 11
      professional RTs were recruited in order to analyze the job competency of
      domestic and international RTs. A draft for the job competency of Korean RTs was
      prepared. A survey was then conducted sampling RTs and the attitudes of their
      competencies were recorded from May 21 to July 30, 2016. RESULTS: We identified
      five modules of professionalism, patient management, health and safety, operation
      of equipment, and procedure management and 131 detailed job competencies for RTs
      in Korea. "Health and safety" had the highest average score and "professionalism"
      had the lowest average score for both job performance and importance. The content
      validity ratios for the 131 subcompetencies were mostly valid. CONCLUSION:
      Establishment of standard guidelines for RT job competency for multidisciplinary
      healthcare at medical institutions may be possible based on our results, which
      will help educators of RT training institutions to clarify their training and
      education.

PMID- 28502974
TI  - Efficacy and Prognostic Value of Partial Sensory Rhizotomy and Microvascular
      Decompression for Primary Trigeminal Neuralgia: A Comparative Study.
AB  - BACKGROUND This study aimed to compare the efficacy and prognostic value of
      partial sensory rhizotomy (PSR) and microvascular decompression (MVD) for primary
      trigeminal neuralgia (PTN). MATERIAL AND METHODS From June 2010 to June 2012, 117
      patients with PTN were recruited for the study, of which 52 cases were treated
      with MVD (the MVD group) and 65 cases were treated with PSR (the PSR group).
      Visual Analog Scoring (VAS) was performed at 1 and 2 weeks, and at 1, 3, and 6
      month after surgery. The overall response rate (ORR) was determined 1 month after
      surgery. Barrow Neurological Institute score was adopted to value the
      reoccurrence at 6, 12, 24, and 36 months after surgery. A 3-year follow-up was
      conducted and the complications were recorded. RESULTS The ORR 2 weeks after
      surgery in the MVD and PSR groups was 98.08% and 84.62%, respectively. One and 2
      weeks after surgery, the VAS was lower in the MVD group than in the PSR group,
      but there was no significant difference in VAS between the 2 groups at 1, 3, and
      6 months after surgery. Three years after surgery, the recurrence rate was
      significantly lower in the MVD group than in the PSR group. The recurrence-free
      survival time was longer in the MVD group than in the PSR group. The occurrence
      rates of herpes and total postoperative complications were significantly higher
      in the PSR group than in the MVD group. CONCLUSIONS Compared with PSR, MVD is
      more suitable for PTN treatment, with less disturbance, lower recurrence rate,
      and better efficacy.

PMID- 28502975
TI  - An Unusual Presentation of Acute Fibrinous and Organizing Pneumonia.
AB  - BACKGROUND Acute fibrinous and organizing pneumonia (AFOP) is a newly evolving
      rare non-infectious lung pathology, characterized by intra-alveolar fibrin balls
      on histology. It is often difficult to diagnose and is usually mistaken for other
      lung pathologies. We present an interesting case of AFOP with unusual radiologic
      findings and disease course. CASE REPORT A 56-year-old woman presented with a 1
      day history of high-grade fever, chills, and profuse sweating. She was febrile to
      101.2 degree Fahrenheit on presentation. On physical examination, she had
      decreased air entry in the left upper lobe of the lung. Laboratory testing showed
      a white cell count of 27,000 cells per microliter of blood with left shift. A
      chest radiograph showed a left upper lobe consolidation. Computed tomography (CT)
      of the chest without intravenous contrast showed advanced centrilobular emphysema
      and left upper lobe consolidation measuring 6.2*5.9 cm. The patient was started
      on antibiotics. She clinically improved and was discharged on oral antibiotics.
      After discharge, a trans-bronchial lung biopsy showed acute inflammatory cell
      infiltrate with intra-alveolar fibrin balls but no hyaline membrane formation or
      significant eosinophils. These findings were consistent with acute fibrinous and
      organizing pneumonia. However, she was subsequently lost to follow-up.
      CONCLUSIONS Our case adds to the literature a new and unusual finding of upper
      lobe infiltrates, in contrast to most cases presenting as bilateral lower lobe
      infiltrates. In our case, symptomatic improvement after antibiotic treatment
      suggests a possible role of antibiotics in management of this entity.

PMID- 28502976
TI  - Technology: Nucleic acid detection - it's elementary with SHERLOCK!

PMID- 28502978
TI  - The opioid receptor triple agonist DPI-125 produces analgesia with less
      respiratory depression and reduced abuse liability.
AB  - Opioid analgesics remain the first choice for the treatment of moderate to severe
      pain, but they are also notorious for their respiratory depression and addictive
      effects. This study focused on the pharmacology of a novel opioid receptor mixed
      agonist DPI-125 and attempted to elucidate the relationship between the delta-,
      MU- and kappa-receptor potency ratio and respiratory depression and abuse
      liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130,
      KUST202 and KUST13T02) were selected for this study. PKA fluorescence
      redistribution assays in CHO cells individually expressing delta-, MU- or kappa
      receptors were used to measure the agonist potency. The respiratory safety
      profiles were estimated in rats by the ratio of ED50 (pCO2 increase)/ED50
      (antinociception). The abuse liability of DPI-125 was evaluated with a self
      administration model in rhesus monkeys. The observed agonist potencies of DPI-125
      for delta-, MU- and kappa-opioid receptors were 4.29+/-0.36, 11.10+/-3.04, and
      16.57+/-4.14 nmol/L, respectively. The other four compounds were also mixed
      agonists with varying potencies. DPI-125 exhibited a high respiratory safety
      profile, clearly related to its high delta-receptor potency. The ratio of the
      EC50 potencies for the MU- and delta-receptors was found to be positively
      correlated with the respiratory safety ratio. DPI-125 has similar potencies for
      MU- and kappa-receptors, which is likely the reason for its reduced abuse
      potential. Our results demonstrate that the opioid receptor mixed agonist DPI-125
      is safer and less addictive than traditional MU-agonist analgesics. These
      findings suggest that the development of delta>MU~kappa opioid receptor mixed
      agonists is feasible, and such compounds could represent a promising class of
      potent analgesics with wider therapeutic windows.

PMID- 28502979
TI  - Chrysin ameliorates podocyte injury and slit diaphragm protein loss via
      inhibition of the PERK-eIF2alpha-ATF-CHOP pathway in diabetic mice.
AB  - Glomerular epithelial podocytes are highly specialized cells that play a crucial
      role in maintaining normal function of the glomerular filtration barrier via
      their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found
      in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer
      properties. This study aimed to evaluate the renoprotective effects of chrysin on
      podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose
      exposed podocytes and in db/db mouse kidneys. Exposure to high glucose (33
      mmol/L) caused glomerular podocyte apoptosis in vitro, which was dose-dependently
      attenuated by nontoxic chrysin (1-20 MUmol/L) through reduction of DNA
      fragmentation. Chrysin treatment dose-dependently restored the increased Bax/Bcl
      2 ratio, and suppressed Apaf-1 induction and the elevated cytochrome c release in
      high glucose-exposed renal podocytes. In diabetic db/db mice, oral administration
      of chrysin (10 mg.kg-1.d-1, for 10 weeks) significantly attenuated proteinuria,
      and alleviated the abnormal alterations in glomerular ultrastructure,
      characterized by apoptotic podocytes and foot process effacement. In addition,
      this compound improved the induction of slit diaphragm proteins podocin/nephrin
      in the diabetic glomeruli. Exposure to high glucose elevated the unfolded protein
      response (UPR) to ER stress in renal podocytes, evidenced by up-regulation of
      PERK-eIF2alpha-ATF4-CHOP. Chrysin treatment blocked such ER stress responses
      pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins
      in vitro and in vivo. These observations demonstrate that targeting ER stress is
      an underlying mechanism of chrysin-mediated amelioration of diabetes-associated
      podocyte injury and dysfunction.

PMID- 28502977
TI  - The evolutionary significance of polyploidy.
AB  - Polyploidy, or the duplication of entire genomes, has been observed in
      prokaryotic and eukaryotic organisms, and in somatic and germ cells. The
      consequences of polyploidization are complex and variable, and they differ
      greatly between systems (clonal or non-clonal) and species, but the process has
      often been considered to be an evolutionary 'dead end'. Here, we review the
      accumulating evidence that correlates polyploidization with environmental change
      or stress, and that has led to an increased recognition of its short-term
      adaptive potential. In addition, we discuss how, once polyploidy has been
      established, the unique retention profile of duplicated genes following whole
      genome duplication might explain key longer-term evolutionary transitions and a
      general increase in biological complexity.

PMID- 28502980
TI  - W2476 ameliorates beta-cell dysfunction and exerts therapeutic effects in mouse
      models of diabetes via modulation of the thioredoxin-interacting protein
      signaling pathway.
AB  - Recent evidence shows that high glucose levels recruit carbohydrate response
      element-binding protein, which binds the promoter of thioredoxin-interacting
      protein (txnip), thereby regulating its expression in beta-cells. Overexpression
      of txnip not only induces beta-cell apoptosis but also reduces insulin
      production. Thus, the discovery of compounds that either inhibit TXNIP activity
      or suppress its expression was the focus of the present study. INS-1E cells
      stably transfected with either a txnip proximal glucose response element
      connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter
      connected to a luciferase reporter plasmid (CL108) were used in primary and
      secondary high-throughput screening campaigns, respectively. From 256 000
      synthetic compounds, a small molecule compound, W2476 [9-((1-(4-acetyl-phenyloxy)
      ethyl)-2-)adenine], was identified as a modulator of the TXNIP-regulated
      signaling pathway following the screening and characterized using a battery of
      bioassays. The preventive and therapeutic properties of W2476 were further
      examined in streptozotocin-induced diabetic and diet-induced obese mice.
      Treatment with W2476 (1, 5, and 15 MUmol/L) dose-dependently inhibited high
      glucose-induced TXNIP expression at the mRNA and protein levels in INS-1E cells
      and rat pancreatic islets. Furthermore, W2476 treatment prevented INS-1E cells
      from apoptosis induced by chronic exposure of high glucose and enhanced insulin
      production in vitro. Oral administration of W2476 (200 mg.kg-1.d-1) rescued
      streptozotocin-induced diabetic mice by promoting beta-cell survival and
      enhancing insulin secretion. This therapeutic property of W2476 was further
      demonstrated by its ability to improve glucose homeostasis and insulin
      sensitivity in diet-induced obese mice. Thus, chemical intervention of the TXNIP
      regulated signaling pathway might present a viable approach to manage diabetes.

PMID- 28502981
TI  - Mechanisms of gene flow in archaea.
AB  - Archaea are diverse, ecologically important, single-celled microorganisms. They
      have unique functions and features, such as methanogenesis and the composition of
      their cell envelope, although many characteristics are shared with the other
      domains of life, either through ancestry or through promiscuous horizontal gene
      transfer. The exchange of genetic material is a major driving force for genome
      evolution across the tree of life and has a role in archaeal speciation,
      adaptation and maintenance of diversity. In this Review, we discuss our current
      knowledge of archaeal mechanisms of DNA transfer and highlight the role of gene
      transfer in archaeal evolution.

PMID- 28502984
TI  - Diabetic nephropathy: Glucose metabolic flux in DN.

PMID- 28502982
TI  - Why are hematopoietic stem cells so 'sexy'? on a search for developmental
      explanation.
AB  - Evidence has accumulated that normal human and murine hematopoietic stem cells
      express several functional pituitary and gonadal sex hormones, and that, in fact,
      some sex hormones, such as androgens, have been employed for many years to
      stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex
      hormone receptors are also expressed by leukemic cell lines and blasts. In this
      review, I will discuss the emerging question of why hematopoietic cells express
      these receptors. A tempting hypothetical explanation for this phenomenon is that
      hematopoietic stem cells are related to subpopulation of migrating primordial
      germ cells. To support of this notion, the anatomical sites of origin of
      primitive and definitive hematopoiesis during embryonic development are tightly
      connected with the migratory route of primordial germ cells: from the proximal
      epiblast to the extraembryonic endoderm at the bottom of the yolk sac and then
      back to the embryo proper via the primitive streak to the aorta-gonado
      mesonephros (AGM) region on the way to the genital ridges. The migration of these
      cells overlaps with the emergence of primitive hematopoiesis in the blood islands
      at the bottom of the yolk sac, and definitive hematopoiesis that occurs in
      hemogenic endothelium in the embryonic dorsal aorta in AGM region.

PMID- 28502985
TI  - Transplantation: Anti-viral therapy enables transplantation of HCV+ kidneys.

PMID- 28502986
TI  - Autoimmunity: HLA-mediated protection in Goodpasture disease.

PMID- 28502987
TI  - Early social isolation impairs development, mate choice and grouping behaviour of
      predatory mites.
AB  - The social environment early in life is a key determinant of developmental,
      physiological and behavioural trajectories across vertebrate and invertebrate
      animals. One crucial variable is the presence/absence of conspecifics. For
      animals usually reared in groups, social isolation after birth or hatching can be
      a highly stressful circumstance, with potentially long-lasting consequences.
      Here, we assessed the effects of social deprivation (isolation) early in life,
      that is, absence of conspecifics, versus social enrichment, that is, presence of
      conspecifics, on developmental time, body size at maturity, mating behaviour and
      group-living in the plant-inhabiting predatory mite Phytoseiulus persimilis.
      Socially deprived protonymphs developed more slowly and were less socially
      competent in grouping behaviour than socially enriched protonymphs. Compromised
      social competence in grouping behaviour was evident in decreased activity, fewer
      mutual encounters and larger interindividual distances, all of which may entail
      severe fitness costs. In female choice/male competition, socially deprived males
      mated earlier than socially enriched males; in male choice/female competition,
      socially deprived females were more likely to mate than socially enriched
      females. In neither mate choice situation did mating duration or body size at
      maturity differ between socially deprived and enriched mating opponents. Social
      isolation-induced shifts in mating behaviour may be interpreted as increased
      attractiveness or competitiveness or, more likely, as hastiness and reduced
      ability to assess mate quality. Overall, many of the social isolation-induced
      behavioural changes in P. persimilis are analogous to those observed in other
      animals such as cockroaches, fruit flies, fishes or rodents. We argue that, due
      to their profound and persistent effects, early social deprivation or enrichment
      may be important determinants in shaping animal personalities.

PMID- 28502988
TI  - Testing Differential Networks with Applications to Detecting Gene-by-Gene
      Interactions.
AB  - Model organisms and human studies have led to increasing empirical evidence that
      interactions among genes contribute broadly to genetic variation of complex
      traits. In the presence of gene-by-gene interactions, the dimensionality of the
      feature space becomes extremely high relative to the sample size. This imposes a
      significant methodological challenge in identifying gene-by-gene interactions. In
      the present paper, through a Gaussian graphical model framework, we translate the
      problem of identifying gene-by-gene interactions associated with a binary trait D
      into an inference problem on the difference of two high-dimensional precision
      matrices, which summarize the conditional dependence network structures of the
      genes. We propose a procedure for testing the differential network globally that
      is particularly powerful against sparse alternatives. In addition, a multiple
      testing procedure with false discovery rate control is developed to infer the
      specific structure of the differential network. Theoretical justification is
      provided to ensure the validity of the proposed tests and optimality results are
      derived under sparsity assumptions. A simulation study demonstrates that the
      proposed tests maintain the desired error rates under the null and have good
      power under the alternative. The methods are applied to a breast cancer gene
      expression study.

PMID- 28502983
TI  - Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD.
AB  - Cardiovascular disease is the main cause of early death in the settings of
      chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing.
      Cardiovascular events can be caused by an imbalance between promoters and
      inhibitors of mineralization, which leads to vascular calcification. This process
      is akin to skeletal mineralization, which is carefully regulated and in which
      isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP
      isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific,
      whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several
      tissues, including bone, liver and kidney. TNALP has a pivotal role in bone
      calcification. Experimental overexpression of TNALP in the vasculature is
      sufficient to induce vascular calcification, cardiac hypertrophy and premature
      death, mimicking the cardiovascular phenotype often found in CKD and T2DM.
      Intestinal ALP contributes to the gut mucosal defence and intestinal and liver
      ALPs might contribute to the acute inflammatory response to endogenous or
      pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular
      calcification, inflammation, and endothelial dysfunction in kidney and
      cardiovascular diseases. We also discuss new drugs that target ALP, which have
      the potential to improve cardiovascular outcomes without inhibiting skeletal
      mineralization.

PMID- 28502989
TI  - A 1024-Channel CMOS Microelectrode Array With 26,400 Electrodes for Recording and
      Stimulation of Electrogenic Cells In Vitro.
AB  - To advance our understanding of the functioning of neuronal ensembles, systems
      are needed to enable simultaneous recording from a large number of individual
      neurons at high spatiotemporal resolution and good signal-to-noise ratio.
      Moreover, stimulation capability is highly desirable for investigating, for
      example, plasticity and learning processes. Here, we present a microelectrode
      array (MEA) system on a single CMOS die for in vitro recording and stimulation.
      The system incorporates 26,400 platinum electrodes, fabricated by in-house post
      processing, over a large sensing area (3.85 * 2.10 mm2) with sub-cellular spatial
      resolution (pitch of 17.5 MUm). Owing to an area and power efficient
      implementation, we were able to integrate 1024 readout channels on chip to record
      extracellular signals from a user-specified selection of electrodes. These
      channels feature noise values of 2.4 MUVrms in the action-potential band (300 Hz
      10 kHz) and 5.4 MUVrms in the local-field-potential band (1 Hz-300 Hz), and
      provide programmable gain (up to 78 dB) to accommodate various biological
      preparations. Amplified and filtered signals are digitized by 10 bit parallel
      single-slope ADCs at 20 kSamples/s. The system also includes 32 stimulation
      units, which can elicit neural spikes through either current or voltage pulses.
      The chip consumes only 75 mW in total, which obviates the need of active cooling
      even for sensitive cell cultures.

PMID- 28502991
TI  - Analysis of Thickness and Quality factor of a Double Paddle Oscillator at Room
      Temperature.
AB  - In this paper, we evaluate the quality (Q) factor and the resonance frequency of
      a double paddle oscillator (DPO) with different thickness using analytical,
      computational and experimental methods. The study is carried out for the 2nd anti
      symmetric resonance mode that provides extremely high experimental Q factors on
      the order of 105. The results show that both the Q factor and the resonance
      frequency of a DPO increase with the thickness at room temperature.

PMID- 28502992
TI  - Religious Involvement and Health over Time: Predictive Effects in a National
      Sample of African Americans.
AB  - In this study, two telephone interviews that assessed both religious involvement
      and health-related quality of life were conducted approximately 2.5 years apart
      in a national sample of 290 African Americans. Religious involvement was assessed
      with an instrument that measured both personal religious beliefs (e.g., having a
      personal relationship with God) and more public religious behaviors (e.g.,
      attending church services). Health-related quality of life was measured with
      version 2 of the Medical Outcomes Study 12-item short form (SF-12v2). Structural
      equation models indicated that higher religious beliefs at baseline predicted
      better physical and mental health 2.5 years later. Higher religious behaviors at
      baseline contributed smaller, complementary suppression effects. Physical and
      mental health indicators from the SF-12v2 at baseline did not predict changes in
      either religious beliefs or religious behaviors over time. These findings
      indicate that, for African Americans, personal religious beliefs lead to
      beneficial health effects over time, whereas individual differences in health do
      not appear to predict changes in religious involvement.

PMID- 28502990
TI  - Short Read Mapping: An Algorithmic Tour.
AB  - Ultra-high-throughput next-generation sequencing (NGS) technology allows us to
      determine the sequence of nucleotides of many millions of DNA molecules in
      parallel. Accompanied by a dramatic reduction in cost since its introduction in
      2004, NGS technology has provided a new way of addressing a wide range of
      biological and biomedical questions, from the study of human genetic disease to
      the analysis of gene expression, protein-DNA interactions, and patterns of DNA
      methylation. The data generated by NGS instruments comprise huge numbers of very
      short DNA sequences, or 'reads', that carry little information by themselves.
      These reads therefore have to be pieced together by well-engineered algorithms to
      reconstruct biologically meaningful measurments, such as the level of expression
      of a gene. To solve this complex, high-dimensional puzzle, reads must be mapped
      back to a reference genome to determine their origin Due to sequencing errors and
      to genuine differences between the reference genome and the individual being
      sequenced, this mapping process must be tolerant of mismatches, insertions, and
      deletions. Although optimal alignment algorithms to solve this problem have long
      been available, the practical requirements of aligning hundreds of millions of
      short reads to the 3 billion base pair long human genome have stimulated the
      development of new, more efficient methods, which today are used routinely
      throughout the world for the analysis of NGS data.

PMID- 28502993
TI  - Mode selection for electrostatic beam resonators based on motional resistance and
      quality factor.
AB  - An analytical comparison between the fundamental mode and higher modes of
      vibration for an electrostatic beam resonator is presented. Multiple mode numbers
      can be matched to a desired resonance frequency through appropriate scaling.
      Therefore, it is important to determine which mode yields the best performance. A
      dynamic model of the resonator is derived and then used to determine the motional
      resistance for each mode. The resulting equation provides the basis for comparing
      performance between modes using motional resistance and quality factor. As a
      demonstration of the approach, a quality factor model that has been previously
      validated experimentally is introduced. Numerical results for silicon resonators
      indicate that the fundamental mode can provide a lower motional resistance and
      higher quality factor when the resonators under comparison have the same aspect
      ratio or the same stiffness.

PMID- 28502994
TI  - Depoling and fatigue behavior of Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystal at
      megahertz frequencies under bipolar electric field.
AB  - Bipolar electric field induced degradation in [001]c poled Pb(Mg1/3Nb2/3)O3
      0.29PbTiO3 (PMN-0.29PT) single crystals was investigated at megahertz
      frequencies. The electromechanical coupling factor kt , dielectric constant
      epsilonr , dielectric loss D, and piezoelectric constant d33 were measured as a
      function of amplitude, frequency, and number of cycles of the applied electric
      field. Our results showed that samples degrade rapidly when the field amplitude
      is larger than a critical value due to the onset of domain switching. We define
      this critical value as the effective coercive field Ec at high frequencies, which
      increases drastically with frequency. We also demonstrate an effective counter
      depoling method by using a dc bias, which could help the design of high field
      driven devices based on PMN-PT single crystals and operated at megahertz
      frequencies.

PMID- 28502995
TI  - The Psycho-Lexical Approach in Exploring the Field of Values: A Reply to
      Schwartz.
AB  - We reply to each of the issues raised by Schwartz in a commentary on our article
      on a comparison of value taxonomies. We discuss two approaches, mentioned in that
      commentary, the lexical approach and the theory-driven approach, especially with
      respect to their capacities in covering the domain of values and with respect to
      the representation of important values in a useful structure. We refute the
      critique by Schwartz that the lexical approach is superfluous, because his theory
      "toward universals in values" would already cover all values, and that their
      mutual relationships are relevant to individuals around the globe. We explain the
      necessity and strength of the lexical approach in taxonomizing the value domain,
      both within and across languages. Furthermore, we argue that principal components
      analysis (PCA) and simultaneous component analysis (SCA) are most adequate in
      arriving at a satisfactory structuring of the great many values in terms of both
      underlying constructs and their facets. We point to a misrepresentation in
      Schwartz's circular model, and we review some misunderstandings on the side of
      Schwartz with respect to our results in comparison with those proceeding from his
      circular model.

PMID- 28502998
TI  - Exploring the Dimensionality of Ethnic Minority Adaptation in Britain: An
      Analysis across Ethnic and Generational Lines.
AB  - In this article I explore the dimensionality of the long-term experiences of the
      main ethnic minority groups (their adaptation) in Britain. Using recent British
      data, I apply factor analysis to uncover the underlying number of factors behind
      variables deemed to be representative of the adaptation experience within the
      literature. I then attempt to assess the groupings of adaptation present in the
      data, to see whether a typology of adaptation exists (i.e. whether adaptation in
      different dimensions can be concomitant with others). The analyses provide an
      empirical evidence base to reflect on: (1) the extent of group differences in the
      adaptation process, which may cut across ethnic and generational lines; and (2)
      whether the uncovered dimensions of adaptation match existing theoretical views
      and empirical evidence. Results suggest that adaptation should be regarded as a
      multi-dimensional phenomenon where clear typologies of adaptation based on
      specific trade-offs (mostly cultural) appear to exist.

PMID- 28502997
TI  - Does measurement invariance hold for the official Mexican multidimensional
      poverty measure? A state-level analysis 2012.
AB  - One of the main goals in poverty measurement is making comparisons of prevalence
      and severity across geographical units. This is attained by merely disaggregating
      the index in question. The underlying assumption is that comparisons across units
      are tenable, inasmuch as the same indicators are utilised for constructing the
      index. Nonetheless, in practice, this assumption is very rarely tested. From the
      statistical perspective, measurement invariance (MI) must hold for comparisons to
      be valid, and violations thereof indicate that a given poverty index measures
      different things across different countries, states, counties, etc. Consequently,
      differentials in severity and prevalence cannot be attributed exclusively to the
      underlying construct (i.e. poverty) but to factors not considered in the measure.
      This article tests whether MI holds for two indexes: the Mexican official
      multidimensional measure (MPM) and an adjusted multidimensional measure (MPM-A)
      that uses less severe thresholds. The analysis is conducted using a novel method
      called the 'alignment method'. It uses these two measures and the method as an
      illustration of why it is vital to introduce MI tests into poverty measurement.
      The results suggest that partial strong MI holds for the official measure and MI
      is violated when the thresholds are adjusted. Partial strong MI guarantees making
      valid comparisons across the 32 states. Should the official measure requires to
      be updated with other thresholds, it would be necessary to adjust the threshold
      or drop the indicator for water deprivation.

PMID- 28502996
TI  - The Influence of the Aromatic Character in the Gas Chromatography Elution Order:
      The Case of Polycyclic Aromatic Hydrocarbons.
AB  - A link between the aromatic character of polycyclic aromatic hydrocarbons and gas
      chromatography elution order in columns with a polysiloxane backbone in the
      stationary phase is reported for the first time. The aromatic character was
      calculated using a method that combines the pi-Sextet Rule and the Pauling Ring
      Bond Orders to allow the establishment of the location and migration of aromatic
      sextets in PAH structures. One GC column with a polysiloxane - like backbone (Rxi
      PAH) and three GC columns with a polysiloxane backbone (DB-5, SE-52, and LC-50),
      were used for the analysis. According to the results of this study, within an
      isomer group, PAHs that contain a lower number of rings affected by the aromatic
      sextets tend to elute earlier than PAHs that contain a higher number of rings
      affected by the aromatic sextets. The PAHs that follow the calculated elution
      order are 88 % in the Rxi-PAH column, 88 % in the DB-5 column, 93 % in the SE-52
      column, and 85% in the LC-50 column. It is expected that future analyses with
      other aromatic compounds in GC columns with a polysiloxane backbone in the
      stationary phase will follow a GC elution order that agrees with the aromatic
      character of the molecules.

PMID- 28502999
TI  - Legal Origin and Social Solidarity: The Continued Relevance of Durkheim to
      Comparative Institutional Analysis.
AB  - By using the classic works of Durkheim as a theoretical platform, this research
      explores the relationship between legal systems and social solidarity. We found
      that certain types of civil law system, most notably those of Scandinavia, are
      associated with higher levels of social capital and better welfare state
      provision. However, we found the relationship between legal system and societal
      outcomes is considerably more complex than suggested by currently fashionable
      economistic legal origin approaches, and more in line with the later writings of
      Durkheim, and, indeed, the literature on comparative capitalisms. Relative
      communitarianism was strongly affected by relative development, reflecting the
      complex relationship between institutions, state capabilities and informal social
      ties and networks.

PMID- 28503001
TI  - Goodness of Fit Tests for Linear Mixed Models.
AB  - Linear mixed models (LMMs) are widely used for regression analysis of data that
      are assumed to be clustered or correlated. Assessing model fit is important for
      valid inference but to date no confirmatory tests are available to assess the
      adequacy of the fixed effects part of LMMs against general alternatives. We
      therefore propose a class of goodness-of-fit tests for the mean structure of
      LMMs. Our test statistic is a quadratic form of the difference between observed
      values and the values expected under the estimated model in cells defined by a
      partition of the covariate space. We show that this test statistic has an
      asymptotic chi-squared distribution when model parameters are estimated by
      maximum likelihood or by least squares and method of moments, and study its power
      under local alternatives both analytically and in simulations. Data on repeated
      measurements of thyroglobulin from individuals exposed to the accident at the
      Chernobyl power plant in 1986 are used to illustrate the proposed test.

PMID- 28503000
TI  - Enantioselective Dirhodium(II)-Catalyzed Cyclopropanations with
      Trimethylsilylethyl and Trichloroethyl Aryldiazoacetates.
AB  - Highly functionalized cyclopropanecarboxylates were readily prepared by rhodium
      catalyzed cyclopropanation of alkenes with aryldiazoacetates and
      styryldiazoaceates, in which the ester functionality is either
      trimethylsilylethyl (TMSE) or trichlorethyl (TCE). By having labile protecting
      groups on the ester, chiral triarylcyclopropane carboxylate ligands were
      conveniently prepared. The asymmetric induction during cyclopropanation is
      dependent on the nature of the ester group and the chiral dirhodium
      tetracarboxylate catalyst. The prolinate catalyst Rh2(S-DOSP)4 was the optimum
      catalyst for asymmetric intermolecular cyclopropanation of TMSE diazoesters with
      styrene, while Rh2(R-BPCP)4 was the optimum catalyst for TCE diazoesters.

PMID- 28503002
TI  - NEUROPSYCHOLOGICAL FUNCTIONING IN PRISONERS WITH AND WITHOUT SELF-INJURIOUS
      BEHAVIORS: Implications for the Criminal Justice System.
AB  - Neuropsychological functioning has not yet been investigated among prisoners who
      engage in self-injurious behaviors, specifically attempted suicide and
      nonsuicidal self-injury (NSSI). The purpose of this study was to investigate
      neuropsychological functioning in prisoners with and without histories of NSSI
      and attempted suicide. The sample consisted of 173 male prisoners referred for
      neuropsychological evaluation. Of participants, 56% reported a history of self
      injury. Performance on the neuropsychological domains of intelligence, memory,
      attention, motor functioning, and executive functioning was assessed. No group
      differences were found among those with NSSI, with NSSI and suicide attempts, and
      with no history of deliberate self-harm, although functioning was poor in all
      domains. Implications of the high prevalence of self-injury in this prison
      sample, as well as implications of impaired functioning on the treatment of self
      injurious behaviors, are discussed.

PMID- 28503003
TI  - Characterization of moderate ash-and-gas explosions at Santiaguito volcano,
      Guatemala, from infrasound waveform inversion and thermal infrared measurements.
AB  - The rapid discharge of gas and rock fragments during volcanic eruptions generates
      acoustic infrasound. Here we present results from the inversion of infrasound
      signals associated with small and moderate gas-and-ash explosions at Santiaguito
      volcano, Guatemala, to retrieve the time history of mass eruption rate at the
      vent. Acoustic waveform inversion is complemented by analyses of thermal infrared
      imagery to constrain the volume and rise dynamics of the eruption plume. Finally,
      we combine results from the two methods in order to assess the bulk density of
      the erupted mixture, constrain the timing of the transition from a momentum
      driven jet to a buoyant plume, and to evaluate the relative volume fractions of
      ash and gas during the initial thrust phase. Our results demonstrate that
      eruptive plumes associated with small-to-moderate size explosions at Santiaguito
      only carry minor fractions of ash, suggesting that these events may not involve
      extensive magma fragmentation in the conduit.

PMID- 28503004
TI  - Factors controlling the evaporation of secondary organic aerosol from alpha
      pinene ozonolysis.
AB  - Secondary organic aerosols (SOA) forms a major fraction of organic aerosols in
      the atmosphere. Knowledge of SOA properties that affect their dynamics in the
      atmosphere is needed for improving climate models. By combining experimental and
      modeling techniques, we investigated the factors controlling SOA evaporation
      under different humidity conditions. Our experiments support the conclusion of
      particle phase diffusivity limiting the evaporation under dry conditions.
      Viscosity of particles at dry conditions was estimated to increase several orders
      of magnitude during evaporation, up to 109 Pa s. However, at atmospherically
      relevant relative humidity and time scales, our results show that diffusion
      limitations may have a minor effect on evaporation of the studied alpha-pinene
      SOA particles. Based on previous studies and our model simulations, we suggest
      that, in warm environments dominated by biogenic emissions, the major uncertainty
      in models describing the SOA particle evaporation is related to the volatility of
      SOA constituents.

PMID- 28503005
TI  - Electron acceleration during streamer collisions in air.
AB  - High-voltage laboratory experiments show that discharges in air, generated over a
      gap of one meter with maximal voltage of 1 MV, may produce X-rays with photon
      energies up to 1 MeV. It has been suggested that the photons are bremsstrahlung
      from electrons accelerated by the impulsive, enhanced field during collisions of
      negative and a positive streamers. To explore this process, we have conducted the
      first self-consistent particle simulations of streamer encounters. Our simulation
      model is a 2-D, cylindrically symmetric, particle-in-cell code tracing the
      electron dynamics and solving the space charge fields, with a Monte Carlo scheme
      accounting for collisions and ionization. We present the electron density, the
      electric field, and the velocity distribution as functions of space and time.
      Assuming a background electric field 1.5 times the breakdown field, we find that
      the electron density reaches 2.1021 m-3, the size of the encounter region is
      ~3.10-12 m3 and that the field enhances to ~9 times the breakdown field during
      ~10-11 s. We further find that the radial component becomes comparable to the
      parallel component, which together with angular scattering leads to an almost
      isotropic distribution of electrons. This is consistent with laboratory
      observations that X-rays are emitted isotropically. However, the maximum energy
      of electrons reached in the simulation is ~600 eV, which is well below the
      energies required to explain observations. The reason is that the encounter
      region is small in size and duration. For the photon energies observed, the field
      must be enhanced in a larger region and/or for a longer time.

PMID- 28503006
TI  - Within-Mother Estimates of the Effects of WIC on Birth Outcomes in New York City.
AB  - There is a large literature suggesting that "WIC works" to improve birth
      outcomes. However, methodological limitations related to selection into the WIC
      program have left room for doubt about this conclusion. This paper uses birth
      records from New York City to address some limitations of the previous
      literature. We estimate models with mother fixed effects to control for fixed
      characteristics of mothers and we directly investigate the way that time-varying
      characteristics of mothers affect selection into the WIC program. We find that
      WIC is associated with reductions in low birth weight, even among full term
      infants, and with reductions in the probability that a child is "small for
      dates." These improvements are associated with a reduction in the probability
      that the mother gained too little weight during pregnancy. Improvements tend to
      be largest for first born children. We also find that women on WIC are more
      likely to be diagnosed with chronic conditions, and receive more intensive
      medical services, a finding that may reflect improved access to medical care.

PMID- 28503008
TI  - A new model order reduction strategy adapted to nonlinear problems in earthquake
      engineering.
AB  - Earthquake dynamic response analysis of large complex structures, especially in
      the presence of nonlinearities, usually turns out to be computationally
      expensive. In this paper, the methodical developments of a new model order
      reduction strategy (MOR) based on the proper orthogonal decomposition (POD)
      method as well as its practical applicability to a realistic building structure
      are presented. The seismic performance of the building structure, a medical
      complex, is to be improved by means of base isolation realized by frictional
      pendulum bearings. According to the new introduced MOR strategy, a set of
      deterministic POD modes (transformation matrix) is assembled, which is derived
      based on the information of parts of the response history, so-called snapshots,
      of the structure under a representative earthquake excitation. Subsequently, this
      transformation matrix is utilized to create reduced-order models of the structure
      subjected to different earthquake excitations. These sets of nonlinear low-order
      representations are now solved in a fractional amount of time in comparison with
      the computations of the full (non-reduced) systems. The results demonstrate
      accurate approximations of the physical (full) responses by means of this new MOR
      strategy if the probable behavior of the structure has already been captured in
      the POD snapshots. Copyright (c) 2016 The Authors. Earthquake Engineering &
      Structural Dynamics Published by John Wiley & Sons Ltd.

PMID- 28503007
TI  - Individual differences in categorical perception of speech: Cue weighting and
      executive function.
AB  - This study examined individual differences in categorical perception and the use
      of multiple acoustic cues in the perception of the stop voicing contrast. Goals
      were to investigate whether gradiency of speech perception was related to
      listeners' differential sensitivity to acoustic cues and to individual
      differences in executive function. The experiment included two speech perception
      tasks (visual analogue scaling [VAS] and anticipatory eye movement [AEM])
      administered to 30 English-speaking adults in two separate experimental sessions.
      Stimuli were a /ta/ to /da/ continuum that systematically varied VOT and f0.
      Findings were that some listeners had a more gradient pattern of responses on the
      VAS task; the listeners who had a gradient response pattern on the VAS task also
      showed more sensitivity to f0 on the AEM task. The patterns were consistent
      across individuals tested on two separate occasions. These results suggest that
      variability in how categorically listeners perceive speech sounds is consistent
      and systematic within individuals.

PMID- 28503009
TI  - Performance of Metal and Polymeric O-Ring Seals during Beyond-Design-Basis
      Thermal Conditions.
AB  - This paper summarizes the small scale thermal exposure test results of the
      performance of metallic and polymeric O-ring seals typically used in radioactive
      material transportation packages. Five different O-ring materials were evaluated:
      Inconel/silver, ethylene-propylene diene monomer (EPDM), polytetrafluoroethylene
      (PTFE), silicone, butyl, and Viton. The overall objective of this study is to
      provide test data and insights to the performance of these Oring seals when
      exposed to beyond-design-basis temperature conditions due to a severe fire. Tests
      were conducted using a small-scale stainless steel pressure vessel pressurized
      with helium to 2 bar or 5 bar at room temperature. The vessel was then heated in
      an electric furnace to temperatures up to 900  degrees C for a pre-determined
      period (typically 8 h to 9 h). The pressure drop technique was used to determine
      if leakage occurred during thermal exposure. Out of a total of 46 tests
      performed, leakage (loss of vessel pressure) was detected in 13 tests.

PMID- 28503010
TI  - Viewpoint: Special Issue on Industrial Robot Agility.

PMID- 28503012
TI  - Volumetric and calorimetric properties of aqueous ionene solutions.
AB  - The volumetric (partial and apparent molar volumes) and calorimetric properties
      (apparent heat capacities) of aqueous cationic polyelectrolyte solutions -
      ionenes - were studied using the oscillating tube densitometer and differential
      scanning calorimeter. The polyion's charge density and the counterion properties
      were considered as variables. The special attention was put to evaluate the
      contribution of electrostatic and hydrophobic effects to the properties studied.
      The contribution of the CH2 group of the polyion's backbone to molar volumes and
      heat capacities was estimated. Synergistic effect between polyion and counterions
      was found.

PMID- 28503011
TI  - When the "Golden Years" Turn Blue: Using the Healthy Aging Literature to
      Elucidate Anxious and Depressive Disorders in Older Adulthood.
AB  - Current treatments for disorders of emotion, like pathological anxiety, are often
      less effective in older adults than in younger adults and have poorly understood
      mechanisms, pointing to the need for psychopathology models that better account
      for age-related changes in normative emotional functioning and the expression of
      disordered emotion. This article describes ways in which the healthy aging and
      emotion literature can enhance understanding and treatment of symptoms of anxiety
      and depression in later life. We offer recommendations for how to integrate the
      healthy aging literatures' theories and findings with psychopathology research
      and clinical practice, and highlight opportunities for future research.

PMID- 28503013
TI  - To Educate or To Incarcerate: Factors in Disproportionality in School Discipline.
AB  - The school-to-prison pipeline describes the process by which school
      suspension/expulsion may push adolescents into the justice system
      disproportionately based on race/ethnicity, socioeconomic status, and gender. The
      current study moves the field forward by analyzing a survey of a diverse sample
      of 2,539 students in 10th to 12th grade in Southern California to examine how
      demographic, individual, and family factors contribute to disparities in office
      referral and suspension/expulsion. African Americans, boys, and students whose
      parents had less education were more likely to be suspended/expelled. Higher
      levels of student academic preparation for class, hours spent on homework, and
      academic aspiration were associated with less school discipline. Findings suggest
      that helping students engage in school may be protective against disproportionate
      school discipline.

PMID- 28503014
TI  - Fathers' Involvement: Correlates and Consequences for Child Socioemotional
      Behavior in the United Kingdom.
AB  - This study investigated longitudinal relationships between fathers' involvement,
      as measured by reading, and child socioemotional behavior between infancy and age
      7 in 9,238 intact two-parent families from the U.K. Millennium Cohort Study, a
      national cohort of British children born between 2000 and 2002. Once a variety of
      covariates and the potential bidirectional nature of relationships were taken
      into account, a path model showed that fathers' involvement with their children
      in infancy significantly predicted better socioemotional behavior at age 3,
      although the relationship was not strong. Fathers' reading with their children
      between ages 3 and 7 was not significantly associated with child socioemotional
      behavior, but mothers' reading with their children at age 3 was significantly
      associated with improved child socioemotional behavior at ages 3 and 5. Results
      also suggested that parenting in the 21st-century British context remains fairly
      gendered. Both mothers and fathers were more likely to engage in physical
      activities with their sons and artistic activities with their daughters. Fathers'
      reading was socially patterned in predicted directions.

PMID- 28503015
TI  - Development and Pilot Randomized Control Trial of a Drama Program to Enhance Well
      being Among Older Adults.
AB  - OBJECTIVE: Develop a novel theatre-based program and test its feasibility,
      tolerability, and preliminary efficacy for improving empathy/compassion and well
      being among older adults. METHOD: Thirteen older adults were randomized to a 6
      week Drama Workshop (DW) program or time-equivalent Backstage Pass (BP) control
      condition. Pre- and post-treatment measures included empathy, compassion, and
      mood scales. Additional post-treatment measures included self-rated change in
      empathy/compassion, confidence, and affect. Participants also rated their
      mood/affect after each session. RESULTS: The program was successfully completed
      and well-liked. No pre-to-post-treatment changes in empathy/compassion or mood
      symptoms were found in either group. Compared to BP, DW weekly ratings indicated
      higher levels of anxiety and lower happiness; however, the DW program had higher
      self-ratings of positive change in self-esteem, confidence, and happiness post
      treatment. DISCUSSION: While the DW may not promote empathy/compassion and was
      personally challenging during the program, engagement in dramatic exercises and
      rehearsing and performing a dramatic piece was seen by participants as a positive
      growth experience, as indicated by the post-treatment ratings of enhanced self
      esteem, confidence and happiness. Thus, such a program might be useful for
      counteracting some of the potential negative aspects of aging, including reduced
      self-efficacy due to physical limitations and negative affect due to losses.

PMID- 28503016
TI  - Comparison of Dichotomized and Distributional Approaches in Rare Event Clinical
      Trial Design: a Fixed Bayesian Design.
AB  - This research was motivated by our goal to design an efficient clinical trial to
      compare two doses of docosahexaenoic acid supplementation for reducing the rate
      of earliest preterm births and/or preterm births. Dichotomizing continuous
      gestational age data using a classic binomial distribution will result in a loss
      of information and reduced power. A distributional approach is an improved
      strategy to retain statistical power from the continuous distribution. However,
      appropriate distributions that fit the data properly, particularly in the tails,
      must be chosen, especially when the data are skewed. A recent study proposed a
      skew-normal method. We propose a three-component normal mixture model and
      introduce separate treatment effects at different components of gestational age.
      We evaluate operating characteristics of mixture model, beta-binomial model, and
      skew-normal model through simulation. We also apply these three methods to data
      from two completed clinical trials from the USA and Australia. Finite mixture
      models are shown to have favorable properties in preterm births analysis but
      minimal benefit for earliest preterm births analysis. Normal models on log
      transformed data have the largest bias. Therefore we recommend finite mixture
      model for preterm births study. Either finite mixture model or beta-binomial
      model is acceptable for earliest preterm births study.

PMID- 28503017
TI  - Automatic localization of landmark sets in head CT images with regression forests
      for image registration initialization.
AB  - Cochlear Implants (CIs) are electrode arrays that are surgically inserted into
      the cochlea. Individual contacts stimulate frequency-mapped nerve endings thus
      replacing the natural electro-mechanical transduction mechanism. CIs are
      programmed post-operatively by audiologists but this is currently done using
      behavioral tests without imaging information that permits relating electrode
      position to inner ear anatomy. We have recently developed a series of image
      processing steps that permit the segmentation of the inner ear anatomy and the
      localization of individual contacts. We have proposed a new programming strategy
      that uses this information and we have shown in a study with 68 participants that
      78% of long term recipients preferred the programming parameters determined with
      this new strategy. A limiting factor to the large scale evaluation and deployment
      of our technique is the amount of user interaction still required in some of the
      steps used in our sequence of image processing algorithms. One such step is the
      rough registration of an atlas to target volumes prior to the use of automated
      intensity-based algorithms when the target volumes have very different fields of
      view and orientations. In this paper we propose a solution to this problem. It
      relies on a random forest-based approach to automatically localize a series of
      landmarks. Our results obtained from 83 images with 132 registration tasks show
      that automatic initialization of an intensity-based algorithm proves to be a
      reliable technique to replace the manual step.

PMID- 28503018
TI  - Intensive woodland management in the Middle Ages: spatial modelling based on
      archival data.
AB  - Firewood played an indispensable role in European socio-economic systems from
      prehistory until the nineteenth century. Recent research has shown that in
      European temperate lowlands the most important management form to produce
      firewood was coppicing. In spite of the growing body of research on traditional
      woodland management, there remain large gaps in knowledge. Detailed studies of
      individual sites or smaller areas have provided a wealth of information on the
      methods of medieval coppicing, and at such sites the long-term effects of
      coppicing on vegetation structure and composition have also been examined.
      However, little is known about the distribution and extent of coppicing at the
      landscape scale, and forming a coherent picture of the spatial extent rather than
      the management details of coppicing in larger regions remains a challenge. This
      paper investigates the distribution and extent of coppice management in Moravia
      (eastern Czech Republic, ca. 22,300 km2) in the Late Middle Ages. We created an
      extensive database of written sources that contained information on the presence
      of coppice woods at the parish level. Subsequently we used the MAXENT algorithm
      to create a model of the distribution of coppicing over the entire area. With the
      help of wood production and consumption estimates, we also calculated the minimum
      area of managed woodland for the study period. Results show that coppicing was
      predominant in the lowlands and often occurred at higher elevations as well,
      where neither natural conditions nor tree species composition were favourable.
      The paper also highlights the potential of spatial models based on archival data
      for historical landscape reconstructions.

PMID- 28503019
TI  - Sources and methods to reconstruct past masting patterns in European oak species.
AB  - The irregular occurrence of good seed years in forest trees is known in many
      parts of the world. Mast year frequency in the past few decades can be examined
      through field observational studies; however, masting patterns in the more
      distant past are equally important in gaining a better understanding of long-term
      forest ecology. Past masting patterns can be studied through the examination of
      historical written sources. These pose considerable challenges, because data in
      them were usually not recorded with the aim of providing information about
      masting. Several studies examined masting in the deeper past, however, authors
      hardly ever considered the methodological implications of using and combining
      various source types. This paper provides a critical overview of the types of
      archival written that are available for the reconstruction of past masting
      patterns for European oak species and proposes a method to unify and evaluate
      different types of data. Available sources cover approximately eight centuries
      and can be put into two basic categories: direct observations on the amount of
      acorns and references to sums of money received in exchange for access to acorns.
      Because archival sources are highly different in origin and quality, the optimal
      solution for creating databases for past masting data is a three-point scale:
      zero mast, moderate mast, good mast. When larger amounts of data are available in
      a unified three-point-scale database, they can be used to test hypotheses about
      past masting frequencies, the driving forces of masting or regional masting
      patterns.

PMID- 28503021
TI  - Validation of tie corroboration and reported alter characteristics among a sample
      of young men who have sex with men.
AB  - The differences between direct ties (i.e., ties between a respondent and their
      nominees) and ties between nominees (indirect) are key to understanding network
      structure, yet remain understudied. Within a sample of 175 young men who have sex
      with men, we explored the corroboration of sex and drug ties, and factors
      associated with corroboration. The majority of instances in which there was no
      corroboration for either sex or drug ties was due to one individual not appearing
      in another respondent's network. When an individual did appear in another
      respondent's network, direct sex and drug ties were corroborated in most cases.
      We also found that more indirect sex ties were corroborated than direct sex ties
      (95.7% vs. 88.9%), but the reverse was true for indirect versus direct drug ties
      (73.1% vs. 84.1%). Strength of relationship and frequency of communication were
      both associated with confirmed direct ties, but not with indirect ties. Based on
      these findings, we recommend that direct and indirect ties be treated differently
      in network analyses.

PMID- 28503020
TI  - Circadian rhythm in mRNA expression of the glutathione synthesis gene Gclc is
      controlled by peripheral glial clocks in Drosophila melanogaster.
AB  - Circadian coordination of metabolism, physiology, and behaviour is found in all
      living kingdoms. Clock genes are transcriptional regulators, and their rhythmic
      activities generate daily rhythms in clock-controlled genes which result in
      cellular and organismal rhythms. Insects provide numerous examples of rhythms in
      behaviour and reproduction, but less is known about control of metabolic
      processes by circadian clocks in insects. Recent data suggest that several
      pathways involved in protecting cells from oxidative stress may be modulated by
      the circadian system, including genes involved in glutathione (GSH) biosynthesis.
      Specifically, rhythmic expression of the gene encoding the catalytic subunit
      (Gclc) of the rate-limiting GSH biosynthetic enzyme was detected in Drosophila
      melanogaster heads. The aim of this study was to determine which clocks in the
      fly multi-oscillatory circadian system are responsible for Gclc rhythms. Genetic
      disruption of tissue-specific clocks in D. melanogaster revealed that
      transcriptional rhythms in Gclc mRNA levels occur independently of the central
      pacemaker neurons, because these rhythms persisted in heads of behaviourally
      arrhythmic flies with a disabled central clock but intact peripheral clocks.
      Disrupting the clock specifically in glial cells abolished rhythmic expression of
      Gclc, suggesting that glia play an important role in Gclc transcriptional
      regulation, which may contribute to maintaining homeostasis in the fly nervous
      system.

PMID- 28503022
TI  - An Early Years Toolbox for Assessing Early Executive Function, Language, Self
      Regulation, and Social Development: Validity, Reliability, and Preliminary Norms.
AB  - Several methods of assessing executive function (EF), self-regulation, language
      development, and social development in young children have been developed over
      previous decades. Yet new technologies make available methods of assessment not
      previously considered. In resolving conceptual and pragmatic limitations of
      existing tools, the Early Years Toolbox (EYT) offers substantial advantages for
      early assessment of language, EF, self-regulation, and social development. In the
      current study, results of our large-scale administration of this toolbox to 1,764
      preschool and early primary school students indicated very good reliability,
      convergent validity with existing measures, and developmental sensitivity.
      Results were also suggestive of better capture of children's emerging abilities
      relative to comparison measures. Preliminary norms are presented, showing a clear
      developmental trajectory across half-year age groups. The accessibility of the
      EYT, as well as its advantages over existing measures, offers considerably
      enhanced opportunities for objective measurement of young children's abilities to
      enable research and educational applications.

PMID- 28503023
TI  - Do resource constraints affect lexical processing? Evidence from eye movements.
AB  - Human language is massively ambiguous, yet we are generally able to identify the
      intended meanings of the sentences we hear and read quickly and accurately. How
      we manage and resolve ambiguity incrementally during real-time language
      comprehension given our cognitive resources and constraints is a major question
      in human cognition. Previous research investigating resource constraints on
      lexical ambiguity resolution has yielded conflicting results. Here we present
      results from two experiments in which we recorded eye movements to test for
      evidence of resource constraints during lexical ambiguity resolution. We embedded
      moderately biased homographs in sentences with neutral prior context and either
      long or short regions of text before disambiguation to the dominant or
      subordinate interpretation. The length of intervening material had no effect on
      ease of disambiguation. Instead, we found only a main effect of meaning at
      disambiguation, such that disambiguating to the subordinate meaning of the
      homograph was more difficult-results consistent with the reordered access model
      and contemporary probabilistic models, but inconsistent with the capacity
      constrained model.

PMID- 28503024
TI  - Remember dax? Relations between children's cross-situational word learning,
      memory, and language abilities.
AB  - Learning new words is a difficult task. Children are able to resolve the
      ambiguity of the task and map words to referents by tracking co-occurrence
      probabilities across multiple moments in time, a behavior termed cross
      situational word learning (CSWL). Although we observe developments in CSWL
      abilities across childhood, the cognitive processes that drive individual and
      developmental change have yet to be identified. This research tested a
      developmental systems account by examining whether multiple cognitive systems co
      contribute to children's CSWL. The results of two experiments revealed that
      multiple cognitive domains, such as memory and language abilities, are likely to
      drive the development of CSWL above and beyond children's age. The results also
      revealed that memory abilities are likely to be particularly important above and
      beyond other cognitive abilities. These findings have implications for theories
      and computational models of CSWL, which typically do not account for individual
      children's cognitive capacities or changes in cognitive capacities across time.

PMID- 28503025
TI  - Gait Speed and Confidence Levels in Persons Using 1 and 2 Canes While Walking a 4
      m Course.
AB  - This is the first article that the researcher is aware of that compares walking
      speed and confidence levels with 1 cane versus 2 canes. An observational study
      was conducted with 30 participants who had difficulty walking. Gait speed was
      assessed on a 4-m course with the participants using 1 cane, then 2 canes. Of 30
      participants, 28 walked faster and demonstrated improved confidence with 2 canes.
      Use of 2 canes with gait might be a technique that people want to consider to
      improve confidence or to improve walking speed, or improve both.

PMID- 28503027
TI  - Introduction to Special Issue: Muslim Cosmopolitanism: Movement, Identity, and
      Contemporary Reconfigurations.

PMID- 28503028
TI  - The Unintentional Procrastination Scale.
AB  - Procrastination refers to the delay or postponement of a task or decision and is
      often conceptualised as a failure of self-regulation. Recent research has
      suggested that procrastination could be delineated into two domains: intentional
      and unintentional. In this two-study paper, we aimed to develop a measure of
      unintentional procrastination (named the Unintentional Procrastination Scale or
      the 'UPS') and test whether this would be a stronger marker of psychopathology
      than intentional and general procrastination. In Study 1, a community sample of
      139 participants completed a questionnaire that consisted of several items
      pertaining to unintentional procrastination that had been derived from theory,
      previous research, and clinical experience. Responses were subjected to a
      principle components analysis and assessment of internal consistency. In Study 2,
      a community sample of 155 participants completed the newly developed scale, along
      with measures of general and intentional procrastination, metacognitions about
      procrastination, and negative affect. Data from the UPS were subjected to
      confirmatory factor analysis and revised accordingly. The UPS was then validated
      using correlation and regression analyses. The six-item UPS possesses construct
      and divergent validity and good internal consistency. The UPS appears to be a
      stronger marker of psychopathology than the pre-existing measures of
      procrastination used in this study. Results from the regression models suggest
      that both negative affect and metacognitions about procrastination differentiate
      between general, intentional, and unintentional procrastination. The UPS is
      brief, has good psychometric properties, and has strong associations with
      negative affect, suggesting it has value as a research and clinical tool.

PMID- 28503026
TI  - A Cognitive-Behavioral Approach to Case Formulations for Nonsuicidal Self-Injury.
AB  - Nonsuicidal self-injury (NSSI) is a highly prevalent behavior among clinical and
      nonclinical samples. Despite the prevalence, maladaptive, and potentially
      dangerous nature of the behavior, no empirically supported interventions have
      been identified specifically for NSSI, and clinicians report a lack of knowledge
      regarding the treatment of NSSI. This article discusses the application of a
      common component of therapy, the case formulation, to conceptualizing and
      treating NSSI. This strategy for case formulation incorporates cognitive
      behavioral and functional analytic approaches while focusing on factors pertinent
      to the development, maintenance, and treatment of NSSI. A case example is
      presented.

PMID- 28503029
TI  - Metal Ion-Responsive Fluorescent Probes for Two-Photon Excitation Microscopy.
AB  - Metal ion-responsive fluorescent probes are powerful tools for visualizing labile
      metal ion pools in live cells. To take full advantage of the benefits offered by
      two-photon excitation microscopy, including increased depth penetration, reduced
      phototoxicity, and intrinsic 3D capabilities, the photophysical properties of the
      probes must be optimized for nonlinear excitation. This review summarizes the
      challenges associated with the design of two-photon excitable fluorescent probes
      and labels and offers an overview on recent efforts in developing selective and
      sensitive reagents for the detection of metal ions in biological systems.

PMID- 28503030
TI  - Ligand-Induced Shape Transformation of PbSe Nanocrystals.
AB  - We present a study of the relation between the surface chemistry and nanocrystal
      shape of PbSe nanocrystals with a variable Pb-to-Se stoichiometry and density of
      oleate ligands. The oleate ligand density and binding configuration are monitored
      by nuclear magnetic resonance and Fourier transform infrared absorbance
      spectroscopy, allowing us to quantify the number of surface-attached ligands per
      NC and the nature of the surface-Pb-oleate configuration. The three-dimensional
      shape of the PbSe nanocrystals is obtained from high-angle annular dark field
      scanning transmission electron microscopy combined with an atom counting method.
      We show that the enhanced oleate capping results in a stabilization and extension
      of the {111} facets, and a crystal shape transformation from a truncated nanocube
      to a truncated octahedron.

PMID- 28503031
TI  - Re-interpreting: Narratives of childhood language brokering over time.
AB  - This article probes how childhood experiences are actively taken into adult lives
      and thus challenges the unwitting and unintentional reproduction of an adult
      child binary in childhood studies. We do this by analyzing interviews with one
      adult daughter of immigrants from Mexico to the United States at four points in
      time (ages 19, 26, 27, and 33). Using narrative analysis to examine the
      mutability of memory, we consider how Eva oriented herself to her childhood
      story, what was salient and invisible in each recount, the values she associated
      with the practice, and the meanings she took from her experiences. We show how
      Eva re-interpreted her experiences as an immigrant child language broker in
      relation to unfolding life events, showing her childhood to be very much alive in
      her adult life. Language brokering serves as one way in which to examine the
      interpenetration of childhood into adulthood, rather than being the focus per se.

PMID- 28503032
TI  - Limestone and Silica Powder Replacements for Cement: Early-Age Performance.
AB  - Developing functional concrete mixtures with less ordinary portland cement (OPC)
      has been one of the key objectives of the 21st century sustainability movement.
      While the supplies of many alternatives to OPC (such as fly ash or slag) may be
      limited, those of limestone and silica powders produced by crushing rocks seem
      virtually endless. The present study examines the chemical and physical
      influences of these powders on the rheology, hydration, and setting of cement
      based materials via experiments and three-dimensional microstructural modeling.
      It is shown that both limestone and silica particle surfaces are active templates
      (sites) for the nucleation and growth of cement hydration products, while the
      limestone itself is also somewhat soluble, leading to the formation of
      carboaluminate hydration products. Because the filler particles are incorporated
      as active members of the percolated backbone that constitutes initial setting of
      a cement-based system, replacements of up to 50 % of the OPC by either of these
      powders on a volumetric basis have minimal impact on the initial setting time,
      and even a paste with only 5 % OPC and 95 % limestone powder by volume achieves
      initial set within 24 h. While their influence on setting is similar, the
      limestone and silica powders produce pastes with quite different rheological
      properties, when substituted at the same volume level. When proceeding from
      setting to later age strength development, one must also consider the dilution of
      the system due to cement removal, along with the solubility/reactivity of the
      filler. However, for applications where controlled (prompt) setting is more
      critical than developing high strengths, such as mortar tile adhesives, grouts,
      and renderings, significant levels of these powder replacements for cement can
      serve as sustainable, functional alternatives to the oft-employed 100 % OPC
      products.

PMID- 28503033
TI  - 15-Deoxy-Delta12,14-prostaglandin J2 Exerts Antioxidant Effects While
      Exacerbating Inflammation in Mice Subjected to Ureteral Obstruction.
AB  - Urinary obstruction is associated with inflammation and oxidative stress, leading
      to renal dysfunction. Previous studies have shown that 15-deoxy-Delta12,14
      prostaglandin J2 (15d-PGJ2) has both antioxidant and anti-inflammatory effects.
      Using a unilateral ureteral obstruction (UUO) mouse model, we examined the
      effects of 15d-PGJ2 on oxidative stress and inflammation in the kidney. Mice were
      subjected to UUO for 3 days and treated with 15d-PGJ2. Protein and RNA expression
      were examined using immunoblotting and qPCR. 15d-PGJ2 increased NF-E2-related
      nuclear factor erythroid-2 (Nrf2) protein expression in response to UUO, and heme
      oxygenase 1 (HO-1), a downstream target of Nrf2, was induced by 15d-PGJ2.
      Additionally, 15d-PGJ2 prevented protein carbonylation, a UUO-induced oxidative
      stress marker. Inflammation, measured by nuclear NF-kappaB, F4/80, and MCP-1, was
      increased in response to UUO and further increased by 15d-PGJ2. Renal injury was
      aggravated by 15d-PGJ2 treatment as measured by kidney injury molecule-1 (KIM-1)
      and cortical caspase 3 content. No effect of 15d-PGJ2 was observed on renal
      function in mice subjected to UUO. This study illustrates differentiated
      functioning of 15d-PGJ2 on inflammation and oxidative stress in response to
      obstructive nephropathy. High concentrations of 15d-PGJ2 protects against
      oxidative stress during 3-day UUO in mice; however, it aggravates the associated
      inflammation.

PMID- 28503034
TI  - Is Postpartum Depression a Disease of Modern Civilization?
AB  - Access to calorie-dense foods, medicine, and other comforts has made modern
      humans healthier than our prehistoric ancestors in many respects. However, the
      epidemics of obesity, diabetes, and cardiovascular disease suggest that there are
      also drawbacks to modern living. Here, we address the question of whether the
      dramatic cultural changes that have occurred over the past century have inflated
      rates of postpartum depression, adding postpartum depression to the list of
      "diseases of modern civilization." We review evidence from cross-cultural,
      epidemiological, and experimental studies documenting associations between
      postpartum depression and modern patterns of early weaning, diets deficient in
      essential fatty acids, low levels of physical activity, low levels of sun
      exposure, and isolation from kin support networks, all of which mark significant
      divergences from lifestyles believed to have been typical throughout human
      evolutionary history. This "mismatch hypothesis" of postpartum depression
      integrates research across diverse research areas and generates novel
      predictions.

PMID- 28503035
TI  - Current Trends in Canine Problem-Solving and Cognition.
AB  - Dogs have occupied a central place in modern comparative cognition, partly
      because of their specific past and present relationship with humans. Over the
      years, we have gained insights about the functioning of the dog's mind, which has
      helped us to understand how dogs' problem-solving abilities differ from those
      present in related species such as the wolf. Novel methodologies are also
      emerging that allow for the study of neural and genetic mechanisms that control
      mental functions. By providing an overview from an ethological perspective, we
      call for greater integration of the field and a better understanding of natural
      dog behavior as a way to generate scientific hypotheses.

PMID- 28503037
TI  - Conference Editorial.

PMID- 28503036
TI  - Clinico-radiological evaluation of retear rate in arthroscopic double row versus
      single row repair technique in full thickness rotator cuff tear.
AB  - BACKGROUND: Rotator cuff tear is most troublesome issue in shoulder surgery.
      Retear is seen in arthroscopically repaired rotator cuff tear. PURPOSE: The
      functional outcome and retear rate in primary full thickness rotator cuff tear
      operated by single and double row repair technique. METHODS: 56 cases with full
      thickness tear of rotator cuff operated by single or double (28 each) were
      studied. Retear rate is evaluated after at least 6 months after surgery. RESULTS:
      There was a statistical difference in retear rate between double row and single
      row repair (p value <0.01). CONCLUSION: Retear rate is low in double row repair
      technique.

PMID- 28503038
TI  - IAPCON 2017 Proceedings.

PMID- 28503040
TI  - Recommendations to Support Nurses and Improve the Delivery of Oncology and
      Palliative Care in India.
AB  - CONTEXT: Nurses in India often practice in resource-constrained settings and care
      for cancer patients with high symptom burden yet receive little oncology or
      palliative care training. AIM: The aim of this study is to explore challenges
      encountered by nurses in India and offer recommendations to improve the delivery
      of oncology and palliative care. METHODS: Qualitative ethnography. SETTING: The
      study was conducted at a government cancer hospital in urban South India. SAMPLE:
      Thirty-seven oncology/palliative care nurses and 22 others (physicians, social
      workers, pharmacists, patients/family members) who interact closely with nurses
      were included in the study. DATA COLLECTION: Data were collected over 9 months
      (September 2011- June 2012). Key data sources included over 400 hours of
      participant observation and 54 audio-recorded semi-structured interviews.
      ANALYSIS: Systematic qualitative analysis of field notes and interview
      transcripts identified key themes and patterns. RESULTS: Key concerns of nurses
      included safety related to chemotherapy administration, workload and clerical
      responsibilities, patients who died on the wards, monitoring family attendants,
      and lack of supplies. Many participants verbalized distress that they received no
      formal oncology training. CONCLUSIONS: Recommendations to support nurses in India
      include: prioritize safety, optimize role of the nurse and explore innovative
      models of care delivery, empower staff nurses, strengthen nurse leadership, offer
      relevant educational programs, enhance teamwork, improve cancer pain management,
      and engage in research and quality improvement projects. Strong institutional
      commitment and leadership are required to implement interventions to support
      nurses. Successful interventions must account for existing cultural and
      professional norms and first address safety needs of nurses. Positive aspects
      from existing models of care delivery can be adapted and integrated into general
      nursing practice.

PMID- 28503039
TI  - The Possible Role of Meditation in Myofascial Pain Syndrome: A New Hypothesis.
AB  - BACKGROUND OF HYPOTHESIS: Myofascial pain syndrome (MPS) is the most common
      musculoskeletal pain disorder of the head and neck area. In the past, several
      theories were put forth to explain its origin and nature, but none proved
      complete. Myofascial pain responds to changing psychological states and stress,
      anxiety, lack of sleep, anger, depression and chronic pain are direct
      contributional factors. Myofascial pain syndrome may be considered as a
      psychosomatic disorder. There are numerous accepted palliative approaches, but of
      all, relaxation techniques stand out and initiate healing at the base level. In
      this article, the connection between mental factors, MPS and meditation are
      highlighted. Recent literature has shed light on the fundamental role of free
      radicals in the emergence of myofascial pain. The accumulating free radicals
      disrupt mitochondrial integrity and function, leading to sustenance and
      progression of MPS. Meditation on the other hand was shown to reduce free radical
      load and can result in clinical improvement. 'Mindfulness' is the working
      principle behind the effect of all meditations, and I emphasize that it can serve
      as a potential tool to reverse the neuro-architectural, neurobiological and
      cellular changes that occur in MPS. CONCLUSIONS: The findings described in this
      paper were drawn from studies on myofascial pain, fibromyalgia, similar chronic
      pain models and most importantly from self experience (experimentation). Till
      date, no hypothesis is available connecting MPS and meditation. Mechanisms
      linking MPS and meditation were identified, and this paper can ignite novel
      research in this direction.

PMID- 28503041
TI  - Pediatric End-of-life Care Barriers and Facilitators: Perception of Nursing
      Professionals in Jordan.
AB  - INTRODUCTION: End-of-life care is a critical issue for pediatric population with
      terminal illness to ensure the best possible quality of care for them and their
      families. A survey was conducted to identify the barriers and facilitators to
      provide pediatric end-of-life care. METHODS: A descriptive cross-sectional study
      was conducted at three tertiary centers providing end-of-life care in Jordan. Two
      hundred critical care nurses were surveyed (response rate 93%). RESULTS: Nurses
      reported moderate level of experience in all areas of delivering pediatric end-of
      life care. The highest scoring of barriers respectively were patients-families
      barriers having deal with angry family member; health-care professional barriers
      multiple physicians, involved with one patient, who differ in opinion about the
      direction care, and where plan of care should go; and organizational barriers not
      available support person for the family. The highest scoring of facilitators
      respectively were of patients families facilitators having family members accept
      that the patient is dying; health-care professional-facilitators having a
      physician agrees about the direction of care, and organizational facilitators
      providing family members adequate time to be alone with the pediatric after he or
      she has died. CONCLUSION: Nurses perceived that patient-family, health-care
      professionals, and organizational related barriers and facilitators were had the
      most influence in providing of pediatric end-of-life care. Findings highlighted
      the need for additional education and support for pediatric staff, across
      professions, in providing pediatric end-of-life care. A pediatric end-of-life
      care team should be developed to assist in improving patients' quality of care
      and increasing the awareness for the need for a standardized tool to evaluate the
      nursing competency level concerning pediatric end-of-life care.

PMID- 28503042
TI  - Assessment of Cancer-related Fatigue among Cancer Patients Receiving Various
      Therapies: A Cross-sectional Observational Study.
AB  - OBJECTIVE: The objective of this cross-sectional, noninterventional 3-month
      observational study was to analyze the prevalence of the cancer-related fatigue
      (CRF) in cancer patient populations with correlation of CRF with different
      treatment modalities. MATERIALS AND METHODS: A descriptive study was carried out
      jointly by the pharmacology and oncology departments of a tertiary care center in
      the Malwa region of Punjab. The data collection was performed by administering
      the validated Brief Fatigue Inventory (BFI) after obtaining the informed consent.
      RESULTS: One hundred and twenty-six cancer patients were recruited with the mean
      age of 49.13 years +/- 14.35 (standard deviation). There are statistical
      correlations found between fatigue and chemotherapy agents such as vinblastine,
      dacarbazine, and cyclophosphamide. CONCLUSION: We observed that CRF is a symptom
      that is experienced by majority of cancer patients, irrespective of the
      diagnosis, or type of treatment received. In addition, assessing CRF before and
      after treatment will facilitate health-care practitioner to treat this symptom.

PMID- 28503044
TI  - Erratum: Impact of Scrambler Therapy on Pain Management and Quality of Life in
      Cancer Patients: A Study of Twenty Cases.
AB  - [This corrects the article on p. 18 in vol. 23, PMID: 28216858.].

PMID- 28503043
TI  - Integration of Specialized Pain Control Services in Palliative Care: A Nationwide
      Web-based Survey.
AB  - INTRODUCTION: Pain control is an important part of palliative care (PC), and
      conventional analgesics do not provide adequate pain relief to all patients. Many
      patients present with complex pain syndromes that require interventional pain
      control measures usually deployed by pain specialists. There is adequate
      integration of specialized pain control services with PC elsewhere, but
      information about the same in our country is lacking. MATERIALS AND METHODS: An
      internet survey was conducted among palliative specialists regarding the need and
      availability of pain specialists for their patients suffering from complex pain
      syndromes. Their attitude toward integrating specialized pain control services in
      their practice was also explored. RESULTS: Majority of palliative physicians came
      across situations where specialists in pain would control the patients' pain
      better. There was a poor availability of such services, and when available, the
      cost was significant. It is heartening to note that though there is poor
      integration of specialized pain control services with palliation, palliative
      physicians acknowledge the need for pain specialists and their techniques for
      providing pain relief for their patients. CONCLUSIONS: Effective pain control is
      needed in palliation, barriers however exist, and there is a need to make pain
      specialists and interventional techniques more freely available.

PMID- 28503045
TI  - Review of Angiotensin-converting Enzyme Inhibitory Assay: Rapid Method in Drug
      Discovery of Herbal Plants.
AB  - The renin-angiotensin-aldosterone system is a signaling pathway which responsible
      in the blood pressure regulation. Angiotensin-converting enzyme (ACE) is one of
      the key elements responsible for the hypertensive mechanism. It converts
      angiotensin-I to angiotensin-II. The discovery history of the ACE inhibitory
      activity assay method has been through a long stage for decades and development
      continues until today. The ACE inhibitory activity has become an effective
      screening method in the search for new antihypertensive agents from herbal
      plants. Some of in vitro assay methods were used to examine the activity of ACE
      inhibitors based on the substrate usage, such as; Cushman and Cheung Method using
      a substrate hippuryl-histidyl-leucine (HHL), Holmquist method using a substrate
      furanacryloyl-tripeptide, Elbl and Wagner method using a substrate benzoil-[l
      14C] glicyl-L-histidine-L-leucine, Carmel and Yaron method using a substrate o
      aminobenzoylglycyl-p-nitrophenylalanilproline, and Lam method using 3
      hydroxybutyrylglycyl-glycyl-glycine as substrate. Several different methods to
      measure the results of enzymatic reactions or separating substrate with products,
      including spectrophotometric, fluorometric, high-performance liquid
      chromatography, electrophoresis, and radiochemistry. Application of the test
      method for screening the ACE inhibitors activity and investigation of active
      compounds from natural products can be done easily with this method, it is very
      helpful in research because the results obtained are simple, accurate, and rapid.

PMID- 28503046
TI  - Reflections about Osteoarthritis and Curcuma longa.
AB  - Osteoarthritis (OA) is a chronic inflammatory degenerative process that affects
      joints such as the hands, hips, shoulders, feet, spine, and especially knees in
      millions of people worldwide. Some authors have shown that Curcuma longa
      components may exhibit benefic effects in the treatment of degenerative diseases
      as OA. This plant belongs to the family Zingiberaceae and it is popularly known
      as turmeric or saffron. This review intended to perform a retrospective search to
      identify studies involving humans and animal models. This review was based on
      articles linking OA and C. longa. Databases as Medline, Science Direct, and
      Lilacs were consulted and a retrospective search was carried out in order to
      identify studies involving humans and animal models. The curcuminoids from C.
      longa exhibit actions at different locations in the pathogenesis of OA once it
      may play an important role as anti-inflammatory, down-regulating enzymes as
      phospholipase A2, cyclooxygenase-2, and lipoxygenases, and reducing tumor
      necrosis factor-alpha-and interleukins such as interleukin-1beta (IL-1beta), IL
      6, and IL-8. They also act as inducer of apoptosis in synoviocytes, decreasing
      the inflammation process and may also reduce the synthesis of reactive oxygen
      species. For these reasons, new pharmaceutical technology and pharmacological
      studies should be proposed to determine the dose, the best delivery vehicle,
      pharmaceutical formulation and route of administration of this plant so its use
      as an adjunct in the treatment of OA may become a reality in clinical practice.

PMID- 28503048
TI  - Antifertility Effect of Bougainvillea spectabilis or Paper Flower.
AB  - Bougainvillea spectabilis (Family: Nyctaginaceae), commonly referred to as Great
      Bougainvillea or Paper Flower, is one of the traditional medicinal plants with
      potential antifertility activity. The aqueous extract and decoction of this plant
      have been used as fertility control among the tribal people in many countries.
      Furthermore, it has been shown to possess anticancer, antidiabetic,
      antihepatotoxic, anti-inflammatory, antihyperlipidemic, antimicrobial,
      antioxidant, and antiulcer properties. Its phytoconstituents such as alkaloids,
      essential oils, flavonoids, glycosides, oxalates, phenolics, phlobotannins,
      quinones, saponins, tannins, and terpenoids were reported as the basis of its
      efficacious therapeutic properties. The other important constituents which
      contribute to the remedial properties are bougainvinones, pinitol, quercetagetin,
      quercetin, and terpinolene. Published information on the antifertility property
      of B. spectabilis was gathered by the use of different database platforms
      including Google Scholar, ScienceDirect, PubMed, SciFinder, and Scopus. These
      database platforms were used to provide an up-to-date review on its importance.

PMID- 28503047
TI  - An Updated Phytopharmacological Review on Medicinal Plant of Arab Region: Apium
      graveolens Linn.
AB  - Apium graveolens Linn. (Karafs) is used in traditional medicine for the treatment
      of the various ailments. There is a need to explore and authenticate the
      pharmacological profile and medicinal importance of the Karafs. In this paper,
      the literature and the published work on Apium were collected using online
      resources "Google scholar", "Web of science", "Scopus" and "PubMed". Each of the
      pharmacological activity was searched individually using the keywords
      "Apium/Karafs/Apium graveolens + individual pharmacological activity". We
      documented the most cited and most recent literatures. The current findings
      illuminate the importance Karafs in the traditional medicine and their impact in
      treating various diseases. This review strongly supports the fact that the Apium
      has emerged as a good source of medicine in treating various diseases. There is
      also a need to isolate the bioactive phytochemicals present in this plant.

PMID- 28503049
TI  - Current Understanding of Antiobesity Property of Capsaicin.
AB  - The capsaicin is an ingredient that we normally mix in food in many cultural
      cuisines even in fresh and dried production. Because of its anticancer,
      anticholesterolemic, antidiabetic, antihypertensive, anti-inflammatory,
      antimicrobial, and antioxidant properties, capsaicin is used worldwide. Moreover,
      capsaicin is also used for the protection of cardiovascular and hepatic diseases.
      The electronic databases PubMed, Scopus, Web of Science, Google Scholar, and
      ScienceDirect were searched since 2000 to present for antiobesity term. This
      review article is provided the update information about the antiobesity property
      and mechanism of capsaicin for further researches.

PMID- 28503050
TI  - Fingerroot, Boesenbergia rotunda and its Aphrodisiac Activity.
AB  - Boesenbergia rotunda (Family: Zingiberaceae) as known as fingerroot is a daily
      food ingredient and traditional medicinal plant in Southeast Asia and Indo-China.
      It has been shown to possess anti-allergic, antibacterial, anticancer, anti
      inflammatory, antioxidant, and antiulcer activities and also shown wound healing.
      Its common phytochemical components include alkaloids, essential oils,
      flavonoids, and phenolics. This plant is rich in boesenbergin, krachaizin,
      panduratin, and pinostrobin, all of which has been reported to contribute to its
      remedial properties including aphrodisiac property. Based on established
      literature on the aphrodisiac property of B. rotunda and possible mode of action,
      this review article has attempted to compile that B. rotunda could be further
      explored for the development of potential aphrodisiac treatment.

PMID- 28503051
TI  - An Update Review on the Anthelmintic Activity of Bitter Gourd, Momordica
      charantia.
AB  - Momordica charantia (Family: Cucurbitales), as known as bitter melon or gourd, is
      a daily consumption as food and traditional medicinal plant in Southeast Asia and
      Indo-China. It has been shown to possess anticancer, antidepressant,
      antidiabetic, anti-inflammatory, antimicrobial, antiobesity, antioxidant, and
      antiulcer properties. Its common phytochemical components include alkaloids,
      charantin, flavonoids, glycosides, phenolics, tannins, and terpenoids. This plant
      is rich in various saponins including momordicin, momordin, momordicoside,
      karavilagenin, karaviloside, and kuguacin, all of which have been reported to
      contribute to its remedial properties including antibacterial, antifungal,
      antiviral, and antiparasitic infections. Based on established literature on the
      anthelmintic activity of M. charantia and possible mode of action, this review
      article has attempted to compile M. charantia could be further explored for the
      development of potential anthelmintic drug.

PMID- 28503052
TI  - Wound Healing Property Review of Siam Weed, Chromolaena odorata.
AB  - Chromolaena odorata (Family: Asteraceae) synonyms as Eupatorium odoratum is a
      traditional medicinal plant that is widely used for its wound healing property.
      In particular, the several parts of this herb have been used to treat wounds,
      burns, and skin infections. Furthermore, it has also been shown to possess
      anticancer, antidiabetic, anti-hepatotoxic, anti-inflammatory, antimicrobial, and
      antioxidant properties. Its phytochemical components are alkaloids, flavonoids,
      flavanone, essential oils, phenolics, saponins, tannins, and terpenoids. The
      other important constituents of this plant are Eupolin, chromomoric acid,
      quercetagetin, and quercetin, all of which contribute to its remedial properties.
      Published information on the wound healing property of C. odorata was gathered by
      the use of different scientific websites such as Google Scholar, Science Direct,
      PubMed, and Web of Knowledge to provide an up-to-date review showing its
      importance.

PMID- 28503053
TI  - Pea, Pisum sativum, and Its Anticancer Activity.
AB  - Pisum sativum (Family: Fabaceae), as known as green pea or garden pea, has long
      been important in diet due to its content of fiber, protein, starch, trace
      elements, and many phytochemical substances. It has been shown to possess
      antibacterial, antidiabetic, antifungal, anti-inflammatory,
      antihypercholesterolemia, and antioxidant activities and also shown anticancer
      property. Its nonnutritive biologically active components include alkaloids,
      flavonoids, glycosides, isoflavones, phenols, phytosterols, phytic acid, protease
      inhibitors, saponins, and tannins. This plant is rich in apigenin,
      hydroxybenzoic, hydroxycinnamic, luteolin, and quercetin, all of which have been
      reported to contribute to its remedial properties including anticarcinogenesis
      property. Based on established literature on the anticancer property of P.
      sativum and possible mode of action, this review article has focused to
      demonstrate that P. sativum could be further explored for the development of
      anticancer treatment.

PMID- 28503054
TI  - A Review on the Pharmacological Activities and Phytochemicals of Alpinia
      officinarum (Galangal) Extracts Derived from Bioassay-Guided Fractionation and
      Isolation.
AB  - The rhizomes of Alpinia officinarum Hance have been used conventionally for the
      treatment of various ailments, triggering a wide interest from the scientific
      research community on this ethnomedicinal plant. This review summarizes the
      phytochemical and pharmacological properties of the extracts and fractions from
      A. officinarum, a plant species of the Zingiberaceae family. Different parts of
      the plant - leaves, roots, rhizomes, and aerial parts - have been extracted in
      various solvents - methanol, ethanol, ethyl acetate, hexane, dichloromethane,
      aqueous, chloroform, and petroleum ether, using various techniques - Soxhlet
      extraction, maceration, ultrasonication, and soaking, whereas fractionation of
      the plant extracts involves the solvent-solvent partition method. The extracts,
      fractions, and isolated compounds have been studied for their biological
      activities - antioxidant, antibacterial, anti-inflammatory, anticancer,
      antiproliferative, inhibition of enzymes, as well as the inhibition of nitric
      oxide production. More findings on A. officinarum are certainly important to
      further develop potential bioactive drug compounds.

PMID- 28503056
TI  - Energy Level Tuning of Poly(phenylene-alt-dithienobenzothiadiazole)s for Low
      Photon Energy Loss Solar Cells.
AB  - Six poly(phenylene-alt-dithienobenzothiadiazole)-based polymers have been
      synthesized for application in polymer-fullerene solar cells. Hydrogen, fluorine,
      or nitrile substitution on benzo-thiadiazole and alkoxy or ester substitution on
      the phenylene moiety are investigated to reduce the energy loss per converted
      photon. Power conversion efficiencies (PCEs) up to 6.6% have been obtained. The
      best performance is found for the polymer-fullerene combination with distinct
      phase separation and crystalline domains. This improves the maximum external
      quantum efficiency for charge formation and collection to 66%. The resulting
      higher photocurrent compensates for the relatively large energy loss per photon
      (Eloss = 0.97 eV) in achieving a high PCE. By contrast, the poly-mer that
      provides a reduced energy loss (Eloss = 0.49 eV) gives a lower photocurrent and a
      reduced PCE of 1.8% because the external quantum efficiency of 17% is limited by
      a suboptimal morphology and a reduced driving force for charge transfer.

PMID- 28503057
TI  - A new bound for the spectral radius of nonnegative tensors.
AB  - By estimating the ratio of the smallest component and the largest component of a
      Perron vector, we provide a new bound for the spectral radius of a nonnegative
      tensor. And it is proved that the proposed result improves the bound in (Li and
      Ng in Numer. Math. 130(2):315-335, 2015).

PMID- 28503058
TI  - Academic Testing Accommodations for ADHD: Do They Help?
AB  - This study investigated the effectiveness of five commonly administered academic
      testing accommodations on reading and math performance in children with attention
      deficit hyperactivity disorder (ADHD). A total of 96 parents of 3rd-8th grade
      students with ADHD participated. More than half of the sample also had parent
      reported learning difficulties in reading and/or math. Individually administered
      cognitive and achievement test scores, types of testing accommodations received,
      and Maryland School Assessment (MSA) reading and math scores were obtained from
      these students' school records. Taking into account grade level and co-occurring
      learning difficulties, none of the five accommodations investigated were
      associated with better MSA scores among students with ADHD who received the
      accommodations versus comparable students who did not. Additionally, individual
      variation in processing speed performance did not moderate the association
      between receipt of accommodations and reading or math performance. Common testing
      accommodations, as presently administered, may offer little benefit for students
      with ADHD, regardless of co-occurring learning difficulties.

PMID- 28503055
TI  - Protein Markers Associated with an ALDH Sub-Population in Colorectal Cancer.
AB  - ALDH has been shown to be a marker that denotes a sub-population of cancer stem
      cells in colorectal and other cancers. This sub-population of cells shows an
      increased risk for tumor initiation, metastasis, and resistance to chemotherapy
      and radiation resulting in recurrence and death. It is thus essential to identify
      the important signaling pathways related to ALDH1+ CSCs in colon cancer. The
      essential issue becomes to isolate pure sub-populations of cells from
      heterogeneous tissues for further analysis. To achieve this goal, tissues from
      colorectal cancer Stage III patients were immuno-stained with ALDH1 antibody.
      Target ALDH1+ and ALDH1- cells from the same tissue were micro-dissected using
      Laser Capture Microdissection (LCM). Captured cells were lysed and analyzed using
      LC-MS/MS where around 20,000 cells were available for analysis. This analysis
      resulted in 134 proteins which were differentially expressed between ALDH1+ and
      ALDH1- cells in three patient sample pairs. Based on these differentially
      expressed proteins an IPA pathway analysis was performed that showed two key
      pathways in cell to cell signaling and organismal injury and abnormalities. The
      IPA analysis revealed beta-catenin, NFkappaB (p65) and TGFbeta1 as important
      cancer-related proteins in these pathways. A TMA validation using
      immunofluorescence staining of tissue micro-arrays including 170 cases was used
      to verify that these key proteins were highly overexpressed in ALDH1+ cells in
      colon cancer tissues compared to ALDH1- cells.

PMID- 28503059
TI  - Developing effective interorganizational relationships between community
      corrections and community treatment providers.
AB  - Weak service coordination between community corrections and community treatment
      agencies is a significant barrier in the diffusion of pharmacotherapy for
      treating opioid and alcohol use disorders. This analysis draws on qualitative
      interviews (n=141) collected in a multisite randomized trial to explore what
      probation/parole officers and treatment staff believe are the most critical
      influences on developing positive interorganizational relationships (IORs)
      between their respective agencies. Officers and treatment staff highlighted
      factors at both the individual and organizational level, with issues related to
      communication surfacing as pivotal. Findings suggest that future interventions
      consider developing shared interagency goals with input at all staff levels.

PMID- 28503060
TI  - Feasibility and Effectiveness of Parent-Child Interaction Therapy with Victims of
      Domestic Violence: A Pilot Study.
AB  - Parent-Child Interaction Therapy (PCIT) is an evidence-based treatment for young
      children (aged 2.5 to 7 years) with externalizing behavior problems. Since its
      development, PCIT has been applied to a wide array of childhood problems and has
      a significant evidence base for families with histories of child physical abuse.
      The current study extended the existing literature by testing the effectiveness
      and feasibility of PCIT in an urban domestic violence shelter with community
      based clinicians delivering the treatment. Seven clinicians implemented PCIT with
      parent-child dyads which included 21 preschool (M = 4.57 years; SD = 1.50)
      children. Families completed assessments at baseline, mid-treatment, and post
      treatment. Nine families completed PCIT (43%). Completion of PCIT was associated
      with improved child behavior, parenting practices, and mental health symptoms.
      Considerations for treatment delivery and future directions are discussed.

PMID- 28503061
TI  - Use of 4-Fr versus 6-Fr Nasobiliary Catheter for Biliary Drainage: A Prospective,
      Multicenter, Randomized, Controlled Study.
AB  - Background and Aim. Endoscopic nasobiliary drainage (NBD) effects according to
      diameter remain unclear. We aimed to assess the drainage effects of the 4-Fr and
      6-Fr NBD catheters. Methods. This prospective, multicenter, randomized,
      controlled study was conducted at Hiroshima University Hospital and related
      facilities within Hiroshima Prefecture. Endoscopic retrograde
      cholangiopancreatography (ERCP) in 246 patients revealed acute cholangitis,
      obstructive jaundice, and/or extrahepatic cholestasis; 4-Fr or 6-Fr NBD catheters
      were randomly allocated and placed in these patients. The primary endpoint was
      the efficacy of NBD based on the technical success rate and clinical success
      (rates of change in blood test and amount of bile output). Secondary endpoints
      included the spontaneous catheter displacement rate and nasal discomfort.
      Results. The technical success rate and clinical success did not differ
      significantly between groups. No spontaneous catheter displacement was noted in
      either group. Nasal discomfort due to catheter placement was significantly lower
      in the 4-Fr group versus the 6-Fr group (24 h after ERCP: 2.4 versus 3.5 cm, P =
      0.005; 48 h after ERCP: 2.2 versus 3.1 cm, P = 0.01). Conclusion. The 4-Fr NBD
      catheter was not inferior to 6-Fr NBD catheter in terms of clinical success; the
      4-Fr NBD catheter was useful to reduce nasal discomfort.

PMID- 28503062
TI  - Contraction Sensing with Smart Braid McKibben Muscles.
AB  - The inherent compliance of soft fluidic actuators makes them attractive for use
      in wearable devices and soft robotics. Their flexible nature permits them to be
      used without traditional rotational or prismatic joints. Without these joints,
      however, measuring the motion of the actuators is challenging. Actuator-level
      sensors could improve the performance of continuum robots and robots with
      compliant or multi-degree-of-freedom joints. We make the reinforcing braid of a
      pneumatic artificial muscle (PAM or McKibben muscle) "smart" by weaving it from
      conductive, insulated wires. These wires form a solenoid-like circuit with an
      inductance that more than doubles over the PAM contraction. The reinforcing and
      sensing fibers can be used to measure the contraction of a PAM actuator with a
      simple, linear function of the measured inductance. Whereas other proposed self
      sensing techniques rely on the addition of special elastomers or transducers, the
      technique presented in this work can be implemented without modifications of this
      kind. We present and experimentally validate two models for Smart Braid sensors
      based on the long solenoid approximation and the Neumann formula, respectively.
      We test a McKibben muscle made from a Smart Braid in quasistatic conditions with
      various end-loads and in dynamic conditions. We also test the performance of the
      Smart Braid sensor alongside steel.

PMID- 28503063
TI  - Severe symptoms of short tear break-up time dry eye are associated with
      accommodative microfluctuations.
AB  - AIM: Validating the hypothesis that accommodative microfluctuations (AMFs) may be
      associated with severe symptoms in short tear break-up time (BUT) dry eye (DE).
      METHODS: This study included 12 subjects with short BUT DE (age: 49.6+/-18.3
      years). Diagnoses were performed based on the presence of DE symptoms, BUT <=5 s,
      Schirmer score >5 mm, and negative keratoconjunctival epithelial damage. Tear
      evaluation, AMF, and functional visual acuity (VA) examinations were conducted
      before and after DE treatment. The AMF parameters evaluated were: total high
      frequency component (HFC), HFC with low accommodation for the task of staring
      into the distance (HFC1), HFC with high accommodation for deskwork (HFC2). A
      subjective questionnaire of DE symptoms was also performed. RESULTS: Mean BUT
      increased from 1.9+/-2.0 to 6.4+/-2.5 s after treatment (P<0.05). The mean
      logarithm of the minimum angle of resolution functional VA significantly improved
      (from 0.19+/-0.19 to 0.12+/-0.17; P<0.05). Mean power spectrum values for total
      HFC and HFC1 decreased (from 61.3+/-5.7 to 53.8+/-6.6 dB and from 62.9+/-10.5 to
      52.4+/-6.2 dB, respectively; P<0.05), while the mean HFC2 power spectrum values
      did not differ before and after treatment (P>0.05). Subjective DE symptoms were
      reduced in nine patients. CONCLUSION: Along with the improvement of BUT after
      treatment, DE symptoms diminished and HFC1 and functional VA improved, suggesting
      that tear film instability is associated with deterioration of functional VA,
      AMF, and DE symptoms.

PMID- 28503064
TI  - Combined intrastromal injection of amphotericin B and topical fluconazole in the
      treatment of resistant cases of keratomycosis: a retrospective study.
AB  - PURPOSE: To evaluate the efficacy of combination therapy of a single intrastromal
      injection of amphotericin B and topical fluconazole in resistant cases of fungal
      keratitis, and also topical amphotericin B as monotherapy in terms of the
      duration of the recovery period and toxic drug effects. METHODS: This
      retrospective 2-year study reviewed 68 cases of unilateral fungal keratitis
      diagnosed by clinical features and positive laboratory culture results. Forty-one
      cases were resistant and did not respond to monotherapy with an antifungal agent.
      Thus, they were treated with a single intrastromal injection of amphotericin B in
      addition to topical fluconazole as combined antifungal therapy, representing
      group A. Twenty-seven cases were treated with topical amphotericin B as
      antifungal monotherapy, representing group B. Topical atropine 1% and different
      antibiotic eye drops were added to the antifungal agents in both groups. Follow
      up of patient records was performed monitoring cure rate, duration of recovery
      period, and toxic drug effects such as pain, burning sensation, and corneal
      melting. RESULTS: The results revealed that group A, treated with combination
      therapy, showed recovery of 34 cases (82.9%) with a mean duration of 24+/-6.42
      days, significantly different from group B which showed recovery of 16 cases
      (59.3%) with a mean duration of 39.66+/-13.6 days. Group A also showed less
      manifestation of drug toxicity than group B. CONCLUSION: Combined intrastromal
      injection of amphotericin B and topical fluconazole can provide a good modality
      in the treatment of resistant cases of fungal keratitis, exhibiting highly potent
      antifungal effects, shorter recovery period, and reduced corneal toxicity.

PMID- 28503065
TI  - Serum cytokine levels related to exposure to volatile organic compounds and PM2.5
      in dwellings and workplaces in French farmers - a mechanism to explain nonsmoking
      COPD.
AB  - Although French farmers smoke less on average than individuals from the general
      population, they suffer more from COPD. Exposure to biological and chemical air
      pollutants in the farm may be the cause of these higher COPD rates. This study
      investigates the role of bio-contaminants, including the relationship of exposure
      to volatile organic compounds (VOCs) and fine particulate matter (of diameter of
      2.5 um [PM2.5]) objectively measured in the farm settings (dwellings and
      workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from
      50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest
      inside the home, while levels of PM2.5 were highest in workplaces (stables and
      granaries). After adjusting for confounders, high exposure to PM2.5 was
      significantly associated with a decreased level of serum cytokines (among others,
      IL13: beta: -0.94, CI: -1.5 to -0.2, P-value =0.004; IL8: beta: -0.82, CI: -1.4
      to -0.2, P-value =0.005) and high exposure to VOCs according to a VOC global
      score with a decreased IL13 level (beta: -0.5, CI: -0.9 to -0.1, P-value =0.01).
      Moreover, respiratory symptoms and diseases, including COPD, were associated with
      a decreased level of serum cytokines significantly in the case of IL5. An
      alteration of immune response balance in terms of cytokine levels in relation to
      indoor chemical air pollution exposure may contribute to respiratory health
      impairment in farmers.

PMID- 28503067
TI  - Interdisciplinary collaboration in reablement - a qualitative study.
AB  - BACKGROUND: In-depth knowledge regarding interdisciplinary collaboration, a key
      feature in reablement, is scarce. OBJECTIVE: To elucidate how the
      interdisciplinary collaboration in reablement worked in a Norwegian context.
      SAMPLE AND METHODS: Seven focus group interviews were conducted with 33 health
      care providers working in interdisciplinary reablement teams in seven
      municipalities across the country. The focus group interviews were transcribed
      and an hermeneutical analysis was conducted. RESULTS: The analysis resulted in
      four main themes: "participant's own goals as a common interdisciplinary
      platform", "a positive professional community", "learning from each other's
      skills and competencies" and "new roles and joint efforts but specific
      competencies". The results show that interdisciplinary collaboration in
      reablement depends on participants defining their own rehabilitation goals, which
      function as a professional unifying platform for the interdisciplinary
      collaboration. The challenges for participants in reablement are often complex
      and include assessments, effort and a need for close collaboration between
      several different professionals. A tight interdisciplinary collaboration causes
      major changes in roles, often from a particular role to a more general role with
      broader job tasks. Although different professionals perform the same
      rehabilitation tasks, it is important that each professional contributes their
      unique competence and thus together they complete each other's competencies.
      CONCLUSION: Factors that have a positive impact on interdisciplinary
      collaboration in reablement are participants' definitions of their goals, number
      and variety of professionals involved, how closely these professionals
      collaborate, the amount of time for communication and shared planning and
      decision making.

PMID- 28503066
TI  - Essential oil-mediated glycerosomes increase transdermal paeoniflorin delivery:
      optimization, characterization, and evaluation in vitro and in vivo.
AB  - In this study, a novel glycerosome carrier containing essential oils was prepared
      for topical administration of paeoniflorin (PF) to enhance its transdermal drug
      delivery and improve drug absorption in the synovium. The formulation of
      glycerosomes was optimized by a uniform design, and the final vehicle was
      composed of 5% (w/v) phospholipid, 0.6% (w/v) cholesterol, and 10% (v/v)
      glycerol, with 2% (v/v) Speranskia tuberculata essential oil (STO) as the
      transdermal enhancer. The in vitro transdermal flux of PF loaded in the STO
      glycerosomes was 1.4-fold, 1.6-fold, and 1.7-fold higher than those of
      glycerosomes, liposomes, and tinctures, respectively. In vivo studies showed that
      the use of STO-glycerosomes was associated with a 3.1-fold greater accumulation
      of PF in the synovium than that of common glycerosomes. This finding was
      confirmed by in vivo imaging studies, which found that the fluorescence intensity
      of Cy5.5-loaded STO-glycerosomes in mice knee joints was 1.8-fold higher than
      that of the common glycerosomes 5 h after administration. The glycerosomes
      mediated by STO exhibited considerable skin permeability as well as improved drug
      absorption in the synovium, indicating that STO-glycerosomes may be a potential
      PF transdermal delivery vehicle for the treatment of rheumatoid arthritis caused
      by synovium lesions.

PMID- 28503068
TI  - A retrospective study on the prognostic value of preoperative
      neutrophil/lymphocyte ratio in patients with primary small-cell carcinoma of the
      esophagus.
AB  - INTRODUCTION: There is increasing evidence that systemic inflammation influences
      the prognosis in patients with malignant tumors. The aim of this research was to
      investigate the prognostic value of neutrophil/lymphocyte ratio (NLR) in patients
      with primary small-cell carcinoma of the esophagus. METHODS: This study
      retrospectively analyzed 129 patients with primary small-cell carcinoma of the
      esophagus who underwent esophagectomy in The Fourth Hospital of Hebei Medical
      University between January 2008 and December 2010. NLRs were calculated by using
      the following formula: peripheral neutrophil count/lymphocyte count (109/L).
      Correlations of NLR with other clinicopathologic data and prognosis were
      analyzed. The survival rate was calculated by Kaplan-Meier analysis. The
      differences between groups were compared by using the log-rank test. Cox
      regression was used to analyze the factors that may affect the survival of the
      patients. RESULTS: The survival rate was found to be related to tumor stage,
      tumor location, nodal metastasis, TNM stage, histology, adjuvant therapy, and NLR
      (all P<0.05). High-NLR group had significantly poorer survival than low-NLR group
      (1-, 3-, and 5-year survival rates: 46.6% vs 57.1%, 21.9% vs 50.0%, and 5.5% vs
      23.2%, respectively, P=0.002). NLR was identified as an independent prognostic
      factor for patients with primary small-cell carcinoma of the esophagus.
      CONCLUSION: NLR is a valuable clinical marker in preoperative estimation as well
      as prognosis prediction for patients with primary small-cell carcinoma of the
      esophagus.

PMID- 28503069
TI  - Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces
      apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells.
AB  - BACKGROUND: Bladder cancer is a common serious disease around the world. Long
      noncoding RNAs (lncRNAs) have been demonstrated to participate in the development
      and progression of various cancers, including bladder cancer. The aim of this
      study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1)
      on proliferation and apoptosis in bladder cancer cell lines and the underlying
      mechanism. METHODS: The levels of TUG1 were detected by quantitative real time
      polymerase chain reaction (qRT-PCR) in bladder cancer tissues and cells. The mRNA
      and protein levels of zinc finger E-box binding homeobox 2 (ZEB2) were measured
      by qRT-PCR and Western blot analysis, respectively. The functional targets of
      TUG1 were predicted by online softwares and confirmed by luciferase reporter
      assay. The effects of TUG1 on cell proliferation and apoptosis were examined by
      MTT and apoptosis assay, respectively. The expression levels of beta-catenin,
      cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis.
      RESULTS: The levels of TUG1 and ZEB2 were significantly increased in bladder
      cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited
      proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2
      overexpression reversed the effects of TUG1 knockdown on cell proliferation and
      apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142
      could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the
      Wnt/beta-catenin pathway by regulating ZEB2 expression in bladder cancer cells.
      CONCLUSION: Downregulation of TUG1 expression inhibited proliferation and induced
      apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through
      the inactivation of Wnt/beta-catenin pathway.

PMID- 28503070
TI  - Tyrosine kinase inhibitor combination therapy in first-line treatment of non
      small-cell lung cancer: systematic review and network meta-analysis.
AB  - INTRODUCTION: The introduction of epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced
      non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients
      develop resistance, with the result that median progression-free survival (PFS)
      is12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a
      promising approach to prolonging remission. This systematic review and network
      meta-analysis (NMA) were undertaken to assess available evidence regarding the
      benefits of first-line combination therapy involving EGFR-TKIs in patients with
      advanced NSCLC. METHODS: Literature searches were performed using relevant search
      terms. Study-level pseudo-individual patient-level data (IPD) were recreated from
      digitized Kaplan-Meier curve data, using a published algorithm. Study IPD were
      analyzed using both the proportional hazards and the acceleration failure time
      (AFT) survival models, and it was concluded that the AFT model was most
      appropriate. An NMA was performed based on acceleration factors (AFs) using a
      Bayesian framework to compare EGFR-TKIs and chemotherapy. RESULTS: Nine
      randomized controlled trials were identified that provided data for EGFR-TKI
      therapy in patients with EGFR+ tumors. These included studies of afatinib (n=3),
      erlotinib (n=3), erlotinib plus bevacizumab (n=1) and gefitinib (n=2). Erlotinib
      plus bevacizumab produced the greatest increase in PFS compared with
      chemotherapy, with 1/AF being 0.24 (95% credible interval [CrI] 0.17, 0.34). This
      combination also produced greater increases in PFS compared with EGFR-TKI
      monotherapy: 1/AF versus afatinib, 0.51 (95% CrI 0.35, 0.73); versus erlotinib,
      0.53 (95% CrI 0.39, 0.72) and versus gefitinib, 0.46 (95% CrI 0.32, 0.66). All
      three EGFR-TKI monotherapies prolonged PFS compared with chemotherapy; estimates
      of treatment effect ranged from 1/AF 0.53 (95% CrI 0.48, 0.60) for gefitinib to
      1/AF 0.46 (95% CrI 0.40, 0.53) for erlotinib. There was no evidence for
      differences between EGFR-TKI monotherapies, as all 95% CrIs included the null
      value. CONCLUSION: Although data for erlotinib plus bevacizumab came from a
      single Phase 2 study, the results of the NMA suggest that adding bevacizumab to
      erlotinib may be a promising approach to improving the outcomes achieved with
      EGFR-TKI monotherapy in patients with advanced EGFR+ NSCLC.

PMID- 28503073
TI  - Response to the publication by Ueberall and Mueller-Schwefe.

PMID- 28503071
TI  - The ecological community of commensal, symbiotic, and pathogenic gastrointestinal
      microorganisms - an appraisal.
AB  - The human gastrointestinal tract is inhabited by a vast population of bacteria,
      numbering ~100 trillion. These microorganisms have been shown to play a
      significant role in digestion, metabolism, and the immune system. The aim of this
      study was to review and discuss how the human body interacts with its gut
      microbiome and in turn the effects that the microorganisms have on its host,
      overall resulting in a true mutualistic relationship.

PMID- 28503072
TI  - Long-term clinical benefit and cost-effectiveness of an 8-week multimodal knee
      osteoarthritis management program incorporating intra-articular sodium
      hyaluronate (Hyalgan(r)) injections.
AB  - BACKGROUND: Given the poor long-term effectiveness of focused nonsurgical knee
      osteoarthritis (OA) treatments, alternative therapies are needed for patients who
      have unsuccessfully exhausted nonsurgical options. METHODS: A telephone interview
      was conducted in patients who participated in a single 8-week multimodal knee OA
      treatment program (mean follow-up: 3.7 years, range: 2.7-4.9 years). The program
      consisted of five intra-articular knee injections of sodium hyaluronate
      (Hyalgan(r)), with each injection given 1 week apart, structured physical
      therapy, knee bracing, and patient education. Clinical outcomes included knee
      pain severity, Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) subscores, current medication use, and history of total knee
      arthroplasty. Base-case, subgroup, and sensitivity analyses were conducted to
      determine the incremental cost-effectiveness ratio (ICER) of the treatment
      program with comparisons made to historical literature controls undergoing usual
      care. RESULTS: A total of 218 patients (54%) provided long-term follow-up data.
      Knee pain severity decreased 60% and WOMAC subscores decreased 33%-42% compared
      to baseline (all p<0.001). Total knee arthroplasty was performed in 22.8%
      (81/356) of knees during followup. The treatment program was highly cost
      effective compared to usual care with a base-case ICER of $6,000 per quality
      adjusted life year (QALY). Results of subgroup analyses, one-way deterministic
      sensitivity analyses, and second-order probabilistic sensitivity analyses
      resulted in ICERs ranging from $3,996 to $10,493 per QALY. The percentage of
      simulations with an ICER below willingness-to-pay limits was 97.2%, 98.9%, and
      99.4% for the $50,000, $100,000, and $150,000 per QALY thresholds, respectively.
      CONCLUSION: Participation in a single 8-week knee OA treatment program, which
      included one cycle of five intra-articular knee injections of sodium hyaluronate
      given at weekly intervals, is highly cost-effective and provides clinically
      meaningful reductions in patient symptoms that are maintained over 3.7 years mean
      follow-up.

PMID- 28503074
TI  - Acute radiation dermatitis in breast cancer patients: challenges and solutions.
AB  - Nearly all women who receive radiotherapy (RT) for breast cancer experience some
      degree of radiation dermatitis. However, evidence describing the appropriate
      management of radiation dermatitis is often lacking or contradictory. Here, we
      summarize the available literature regarding radiation dermatitis causes, the
      presentation and timing of symptoms, methods for dermatitis assessment and
      prevention, and review evidence-based management strategies.

PMID- 28503076
TI  - Positive predictive value of peptic ulcer diagnosis codes in the Danish National
      Patient Registry.
AB  - BACKGROUND: Diagnoses of peptic ulcer are registered in the Danish National
      Patient Registry (DNPR) for administrative as well as research purposes, but it
      is unknown whether the coding validity depends on the location of the ulcer.
      OBJECTIVE: To validate the International Classification of Diseases, 10th
      revision diagnosis codes of peptic ulcer in the DNPR by estimating positive
      predictive values (PPVs) for gastric and duodenal ulcer diagnoses. METHODS: We
      identified all patients registered with a hospital discharge diagnosis of peptic
      ulcer from Aarhus University Hospital, Denmark, in 1995-2006. Among them, we
      randomly selected 200 who had an outpatient gastroscopy at the time of ulcer
      diagnosis. We reviewed the findings from these gastroscopies to confirm the
      presence of peptic ulcer and its location. We calculated PPVs and corresponding
      95% confidence intervals (CIs) of gastric and duodenal ulcer diagnoses, using
      descriptions from the gastroscopic examinations as standard reference. RESULTS:
      In total, 182 records (91%) were available for review. The overall PPV of peptic
      ulcer diagnoses in DNPR was 95.6% (95% CI 91.5-98.1), with PPVs of 90.3% (95% CI
      82.4-95.5) for gastric ulcer diagnoses, and 94.4% (95% CI 87.4-98.2) for duodenal
      ulcer diagnoses. PPVs were constant over time. CONCLUSION: The PPV of
      uncomplicated peptic ulcer diagnoses in the DNPR is high, and the location of the
      ulcers is registered correctly in most cases, indicating that the diagnoses are
      useful for research purposes.

PMID- 28503075
TI  - Imprint cytology versus frozen section analysis for intraoperative assessment of
      sentinel lymph node in breast cancer.
AB  - INTRODUCTION: Sentinel lymph node (SLN) biopsy is the gold standard for surgical
      staging of the axilla in breast cancer (BC). Frozen section (FS) remains the most
      popular means of intraoperative SLN diagnosis. Imprint cytology (IC) has also
      been suggested as a less expensive and equally accurate alternative to FS. The
      aim of our study was to perform a direct comparison between IC and FS on the same
      SLNs of BC cases operated in a single center by the same surgical team. MATERIALS
      AND METHODS: Into this prospective study we enrolled 60 consecutive patients with
      histologically proven T1-T3 BC and clinically negative axilla. Sentinel nodes
      were detected using a standard protocol. The SLN(s) was always assessed by IC as
      well as FS analysis and immunohistochemistry. Nevertheless, all intraoperative
      decisions were based on FS analysis. RESULTS: During the study period 60 patients
      with invasive BC were registered, with 80 SLNs harvested. Mean number of SLN(s)
      identified for each patient was 1.33. The sensitivity and specificity were 90%
      and 100%, respectively, for IC, and 80% and 100% for FS. Relevant
      positive/negative predictive values were 100%/98% for IC and 100%/96.15%,
      respectively, for FS. Overall accuracy was 98% for IC and 97% for FS. Therefore,
      statistically significant difference between the two methods in the detection of
      positive nodes was not elucidated (p=1.000). CONCLUSIONS: IC appeared to be
      marginally more sensitive than FS in detecting SLN metastatic activity. Overall
      accuracy was 98.75%. With regard to the primary lesion characteristics, we
      conclude that initial lesion size and lymphovascular invasion play a pivotal role
      in metastatic involvement of the SLN with the dimensions of metastasis bearing no
      correlation with tumor size. Therefore, IC appears to be a sensitive and accurate
      method for the intraoperative assessment of SLN in BC patients, but further
      studies are required to confirm this interesting data.

PMID- 28503077
TI  - An unusual association of headache, epilepsy, and late-onset Kleist's
      pseudodepression syndrome in frontal lobe cavernoma of the cerebral left
      hemisphere.
AB  - Cerebral cavernous angioma or cavernoma is a benign vascular malformation,
      usually asymptomatic. It is infrequent and often its discovery is incidental, a
      so-called incidentaloma. However, these lesions can be symptomatic, causing
      headaches, epilepsy, cerebral hemorrhage and other neurological signs depending
      on the brain area involved. Frontal localization is responsible for psychiatric
      disorders, particularly the prefrontal region, leading to prefrontal syndrome, a
      condition common in all frontal lobe tumors. Psychopathological syndrome can be
      depression-type, pseudodepression syndrome or maniac-type, pseudomaniac syndrome.
      Surgical treatment of lesions like this may not always be possible due to their
      location in eloquent areas. In this study, we describe an unusual association of
      migraine-like headache, epilepsy and frontal lobe pseudodepression late-onset
      syndrome in the same patient. We have considered this case interesting mainly for
      the rarity of both a headache with migraine features and for the late onset of
      pseudodepression syndrome. Pathophysiology underlying migraine-like headache and
      that concerning the late-onset pseudodepression frontal lobe syndrome seems to be
      unclear. This case leads to further hypotheses about the mechanisms responsible
      for headache syndromes and psychopathological disorders, in the specific case
      when caused by a cerebral frontal lobe lesion.

PMID- 28503079
TI  - Using mobile audience response systems to enhance medical education: a medical
      student perspective.

PMID- 28503080
TI  - A Bayesian mixture model for missing data in marine mammal growth analysis.
AB  - Much of what is known about bottle nose dolphin (Tursiops truncatus) anatomy and
      physiology is based on necropsies from stranding events. Measurements of total
      body length, total body mass, and age are used to estimate growth. It is more
      feasible to retrieve and transport smaller animals for total body mass
      measurement than larger animals, introducing a systematic bias in sampling.
      Adverse weather events, volunteer availability, and other unforeseen
      circumstances also contribute to incomplete measurement. We have developed a
      Bayesian mixture model to describe growth in detected stranded animals using data
      from both those that are fully measured and those not fully measured. Our
      approach uses a shared random effect to link the missingness mechanism (i.e.
      full/partial measurement) to distinct growth curves in the fully and partially
      measured populations, thereby enabling drawing of strength for estimation. We use
      simulation to compare our model to complete case analysis and two common multiple
      imputation methods according to model mean square error. Results indicate that
      our mixture model provides better fit both when the two populations are present
      and when they are not. The feasibility and utility of our new method is
      demonstrated by application to South Carolina strandings data.

PMID- 28503078
TI  - Variations in the clinical practice of physicians managing Takayasu arteritis: a
      nationwide survey.
AB  - OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis that
      predominately affects young women and can cause severe ischemic complications.
      Given the rarity of TAK, the management of this condition is challenging. We aim
      to describe current rheumatologist practices for the management of TAK and
      identify discrepancies and gaps in knowledge. METHODS: An online survey
      (developed by the Canadian Vasculitis Network and approved by the Canadian
      Rheumatology Association) containing 48 questions with regard to the diagnosis,
      monitoring and treatment of TAK was distributed to 495 Canadian adult and
      pediatric rheu-matologists by email. RESULTS: Sixty-six rheumatologists completed
      the survey (13% response rate): the majority (73%) were from academic centers and
      <=25% reported managing more than ten patients in their career. For establishing
      the diagnosis of TAK, they relied on a combination of signs and symptoms of
      ischemia, elevations of inflammatory markers and vascular imaging (typically
      computed tomography and magnetic resonance angiography). The frequency of
      monitoring for disease activity and the methods employed (clinical, laboratory or
      imaging) were variable. All physicians used corticosteroids for the treatment of
      TAK, but 42% would treat for at least 6-12 months, 26% for 12-24 months and 23%
      would never stop corticosteroids. Fifty-three percent would always use an
      immunosuppressant (most commonly methotrexate or azathioprine) in addition to
      corticosteroids and the remainder would only start an immunosuppressant in
      patients with refractory or relapsing disease. CONCLUSION: Physician practices
      for the management of TAK are variable, suggesting that there are knowledge gaps,
      which may impact outcomes in patients with TAK.

PMID- 28503081
TI  - Feeding intolerance, inflammation, and neurobehaviors in preterm infants.
AB  - PURPOSE: Identifying relationships between feeding intolerance (FI),
      inflammation, and early measures of neurodevelopment may provide the basis for
      clinically relevant assessments for NICU clinicians and staff. The purpose of
      this secondary analysis was to examine the relationship of FI to inflammatory
      markers and/or neurobehaviors in the first week of life. METHODS: This was a
      retrospective, matched case-control design with data drawn from 114 infants born
      at <=32 weeks gestation. RESULTS: Eight infants developed FI prior to full
      enteral feedings. These infants were more likely to have dysregulated levels of
      cytokines, specifically IL6, and lower neurodevelopmental scores compared to
      infants without FI. CONCLUSIONS: Results suggest physiologic dysregulation and an
      immature nervous system may contribute to the phenomenon of FI in preterm
      infants. Further research to identify the role of the brain-gut-immune axis on FI
      and other GI complications in this population is warranted.

PMID- 28503082
TI  - Postcolonial penality: Liberty and repression in the shadow of independence,
      India c. 1947.
AB  - This article reports primary archival data on the colonial penal history of
      British India and its reconfiguration into the postcolonial Indian state. It
      introduces criminologists to frameworks through which postcolonial scholars have
      sought to make sense of the continuities and discontinuities of rule across the
      colonial/postcolonial divide. The article examines the postcolonial life of one
      example of colonial penal power, known as the criminal tribes policy, under which
      more than three million Indian subjects of British rule were restricted in their
      movements, subject to a host of administrative rules and sometimes severe
      punishments, sequestered in settlements and limited in access to legal redress.
      It illustrates how at the birth of the postcolonial Indian state, encompassing
      visions of a liberal, unfettered and free life guaranteed in a new Constitution
      and charter of Fundamental Rights, freedom for some was to prove as elusive as
      citizens as it had been as subjects.

PMID- 28503083
TI  - Vegetation resurvey is robust to plot location uncertainty.
AB  - AIM: Resurveys of historical vegetation plots are increasingly used for the
      assessment of decadal changes in plant species diversity and composition.
      However, historical plots are usually relocated only approximately. This
      potentially inflates temporal changes and undermines results. LOCATION: Temperate
      deciduous forests in Central Europe. METHODS: To explore if robust conclusions
      can be drawn from resurvey studies despite location uncertainty, we compared
      temporal changes in species richness, frequency, composition and compositional
      heterogeneity between exactly and approximately relocated plots. We hypothesized
      that compositional changes should be lower and changes in species richness should
      be less variable on exactly relocated plots, because pseudo-turnover inflates
      temporal changes on approximately relocated plots. RESULTS: Temporal changes in
      species richness were not more variable and temporal changes in species
      composition and compositional heterogeneity were not higher on approximately
      relocated plots. Moreover, the frequency of individual species changed similarly
      on both plot types. MAIN CONCLUSIONS: The resurvey of historical vegetation plots
      is robust to uncertainty in original plot location and, when done properly,
      provides reliable evidence of decadal changes in plant communities. This provides
      important background for other resurvey studies and opens up the possibility for
      large-scale assessments of plant community change.

PMID- 28503084
TI  - Carbon Dioxide Utilization by the Five-Membered Ring Products of Cyclometalation
      Reactions.
AB  - In carbon dioxide utilization by cyclometalated five-membered ring products, the
      following compounds are used in four types of applications: 1. 2-Phenylpyrazole
      iridium compounds, pincer phosphine iridium compounds and 2-phenylimidazoline
      iridium compounds are used as catalysts for both formic acid production from CO2
      and H2, and hydrogen production from the formic acid. This formic acid can be a
      useful agent for H2 production and storage for fuel cell electric vehicles. 2.
      Other chemicals, e.g., dimethyl carbonate, methane, methanol and CO, are produced
      with dimethylaminomethylphenyltin compounds, pincer phosphine iridium compounds,
      pincer phosphine nickel compound and ruthenium carbene compound or 2
      phenylpyridine iridium compounds, and phenylbenzothiazole iridium compounds as
      the catalysts for the reactions with CO2. 3. The five-membered ring intermediates
      of cyclometalation reactions with the conventional substrates react with carbon
      dioxide to afford their many types of carboxylic acid derivatives. 4. Carbon
      dioxide is easily immobilized at room temperature with immobilizing agents such
      as pincer phosphine nickel compounds, pincer phosphine palladium compounds,
      pincer N,N-dimethylaminomethyltin compounds and tris(2-pyridylthio)methane zinc
      compounds.

PMID- 28503086
TI  - Anticancer Natural Compounds: Molecular Mechanisms and Functions. Part I.

PMID- 28503085
TI  - Physicochemical properties and in vitro cytotoxicity of iron oxide-based
      nanoparticles modified with antiangiogenic and antitumor peptide A7R.
AB  - Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers
      as targeted drug delivery vehicles, because they can be guided to their target
      with the help of an external magnetic field. Functionalization of nanoparticles'
      surface with molecules, which bind with high affinity to receptors on target
      tissue significantly facilitates delivery of coated nanoparticles to their
      targeted site. Here, we demonstrate conjugation of an antiangiogenic and
      antitumor peptide ATWLPPR (A7R) to SPIONs modified with sebacic acid (SPIONs-SA).
      Successful conjugation was confirmed by various analytical techniques (FTIR,
      SERS, SEM-EDS, TEM, TGA). Cell cytotoxicity studies, against two cell lines
      (HUVEC and MDA-MB-231) indicated that SPIONs modified with A7R reduced HUVEC cell
      viability at concentrations higher than 0.01 mg Fe/mL, in comparison to cells
      that were exposed to either the nanoparticles modified with sebacic acid or A7R
      peptide solely, what might be partially caused by a process of internalization.

PMID- 28503088
TI  - Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with
      Nature to Triumph Over Lernaean Hydra.
AB  - Cancer is a multifaceted disease. Our deepened knowledge about genetic and
      biological mechanisms of cancer cells presents an opportunity to explore the
      inter-individual differences in the body's ability to metabolize and respond to
      different nutrients. It is becoming progressively more understandable that the
      deregulation of several signaling pathways and the alterations in apoptotic
      response are some of the major determinants that underpin carcinogenesis. Tumor
      necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-mediated signaling has
      gained a remarkable appreciation because of its ability to selectively induce
      apoptosis in cancer cells leaving normal cells intact. However, technological
      advances have started to shed light on underlying mechanisms of resistance
      against TRAIL-induced apoptosis in cancer cells. The impairment of TRAIL-mediated
      apoptosis includes various factors ranging from the loss or down regulation of
      TRAIL receptors or pro-apoptotic proteins to the up regulation of anti-apoptotic
      proteins. Intriguingly to mention that there is an ever-increasing number of
      natural herbal extracts (phytometabolites), which have been explored to date for
      their potential action in restoring apoptosis TRAIL-mediated in cancer cells. In
      this review, we will highlight the progress in understanding the mechanisms opted
      by phenolic compounds in overcoming TRAIL resistance.

PMID- 28503089
TI  - Anticancer Chemodiversity of Ranunculaceae Medicinal Plants: Molecular Mechanisms
      and Functions.
AB  - The buttercup family, Ranunculaceae, comprising more than 2,200 species in at
      least 62 genera, mostly herbs, has long been used in folk medicine and worldwide
      ethnomedicine since the beginning of human civilization. Various medicinal
      phytometabolites have been found in Ranunculaceae plants, many of which, such as
      alkaloids, terpenoids, saponins, and polysaccharides, have shown anti-cancer
      activities in vitro and in vivo. Most concerns have been raised for two epiphany
      molecules, the monoterpene thymoquinone and the isoquinoline alkaloid berberine.
      At least 17 genera have been enriched with anti-cancer phytometabolites. Some
      Ranunculaceae phytometabolites induce the cell cycle arrest and apoptosis of
      cancer cells or enhance immune activities, while others inhibit the
      proliferation, invasion, angiogenesis, and metastasis, or reverse the multi-drug
      resistance of cancer cells thereby regulating all known hallmarks of cancer.
      These phytometabolites could exert their anti-cancer activities via multiple
      signaling pathways. In addition, absorption, distribution, metabolism, and
      excretion/toxicity properties and structure/activity relationships of some
      phytometabolites have been revealed assisting in the early drug discovery and
      development pipelines. However, a comprehensive review of the molecular
      mechanisms and functions of Ranunculaceae anti-cancer phytometabolites is
      lacking. Here, we summarize the recent progress of the anti-cancer chemo- and
      pharmacological diversity of Ranunculaceae medicinal plants, focusing on the
      emerging molecular machineries and functions of anti-cancer phytometabolites.
      Gene expression profiling and relevant omics platforms (e.g. genomics,
      transcriptomics, proteomics, and metabolomics) could reveal differential effects
      of phytometabolites on the phenotypically heterogeneous cancer cells.

PMID- 28503090
TI  - Compounds From Celastraceae Targeting Cancer Pathways and Their Potential
      Application in Head and Neck Squamous Cell Carcinoma: A Review.
AB  - Squamous cell carcinoma of the head and neck is one of the most common cancer
      types worldwide. It initiates on the epithelial lining of the upper aerodigestive
      tract, at most instances as a consequence of tobacco and alcohol consumption.
      Treatment options based on conventional therapies or targeted therapies under
      development have limited efficacy due to multiple genetic alterations typically
      found in this cancer type. Natural products derived from plants often possess
      biological activities that may be valuable in the development of new therapeutic
      agents for cancer treatment. Several genera from the family Celastraceae have
      been studied in this context. This review reports studies on chemical
      constituents isolated from species from the Celastraceae family targeting cancer
      mechanisms studied to date. These results are then correlated with molecular
      characteristics of head and neck squamous cell carcinoma in an attempt to
      identify constituents with potential application in the treatment of this complex
      disease at the molecular level.

PMID- 28503087
TI  - Established Human Cell Lines as Models to Study Anti-leukemic Effects of
      Flavonoids.
AB  - Despite the extensive work on pathological mechanisms and some recent advances in
      the treatment of different hematological malignancies, leukemia continues to
      present a significant challenge being frequently considered as incurable disease.
      Therefore, the development of novel therapeutic agents with high efficacy and low
      toxicity is urgently needed to improve the overall survival rate of patients. In
      this comprehensive review article, the current knowledge about the anticancer
      activities of flavonoids as plant secondary polyphenolic metabolites in the most
      commonly used human established leukemia cell lines (HL-60, NB4, KG1a, U937, THP
      1, K562, Jurkat, CCRF- CEM, MOLT-3, and MOLT-4) is compiled, revealing clear anti
      proliferative, pro-apoptotic, cell cycle arresting, and differentiation inducing
      effects for certain compounds. Considering the low toxicity of these substances
      in normal blood cells, the presented data show a great potential of flavonoids to
      be developed into novel anti-leukemia agents applicable also in the malignant
      cells resistant to the current conventional chemotherapeutic drugs.

PMID- 28503092
TI  - Management of Gene Variants of Unknown Significance: Analysis Method and Risk
      Assessment of the VHL Mutation p.P81S (c.241C>T).
AB  - BACKGROUND: Evaluation of the pathogenicity of a gene variant of unknown
      significance (VUS) is crucial for molecular diagnosis and genetic counseling, but
      can be challenging. This is especially so in phenotypically variable diseases,
      such as von Hippel-Lindau disease (vHL). vHL is caused by germline mutations in
      the VHL gene, which predispose to the development of multiple tumors such as
      central nervous system hemangioblastomas and renal cell carcinoma (RCC).
      OBJECTIVE: We propose a method for the evaluation of VUS pathogenicity through
      our experience with the VHL missense mutation c.241C>T (p.P81S). METHOD: 1)
      Clinical evaluation of known variant carriers: We evaluated a family of five VHL
      p.P81S carriers, as well as the clinical characteristics of all the p.P81S
      carriers reported in the literature; 2) Evaluation of tumor tissue via genetic
      analysis, histology, and immunohistochemistry (IHC); 3) Assessment of the
      variant's impact on protein structure and function, using multiple databases, in
      silico algorithms, and reports of functional studies. RESULTS: Only one family
      member had clinical signs of vHL with early-onset RCC. IHC analysis showed no VHL
      protein expressed in the tumor, consistent with biallelic VHL inactivation. The
      majority of in silico algorithms reported p.P81S as possibly pathogenic in
      relation to vHL or RCC, but there were discrepancies. Functional studies suggest
      that p.P81S impairs the VHL protein's function. CONCLUSION: The VHL p.P81S
      mutation is most likely a low-penetrant pathogenic variant predisposing to RCC
      development. We suggest the above-mentioned method for VUS evaluation with use of
      different methods, especially a variety of in silico methods and tumor tissue
      analysis.

PMID- 28503093
TI  - Alarms about structural alerts.
AB  - Structural alerts are widely accepted in chemical toxicology and regulatory
      decision support as a simple and transparent means to flag potential chemical
      hazards or group compounds into categories for read-across. However, there has
      been a growing concern that alerts disproportionally flag too many chemicals as
      toxic, which questions their reliability as toxicity markers. Conversely, the
      rigorously developed and properly validated statistical QSAR models can
      accurately and reliably predict the toxicity of a chemical; however, their use in
      regulatory toxicology has been hampered by the lack of transparency and
      interpretability. We demonstrate that contrary to the common perception of QSAR
      models as "black boxes" they can be used to identify statistically significant
      chemical substructures (QSAR-based alerts) that influence toxicity. We show
      through several case studies, however, that the mere presence of structural
      alerts in a chemical, irrespective of the derivation method (expert-based or QSAR
      based), should be perceived only as hypotheses of possible toxicological effect.
      We propose a new approach that synergistically integrates structural alerts and
      rigorously validated QSAR models for a more transparent and accurate safety
      assessment of new chemicals.

PMID- 28503094
TI  - The nature, characteristics and associations of care home staff stress and
      wellbeing: a national survey.
AB  - BACKGROUND: The majority of residents in care homes in the United Kingdom are
      living with dementia or significant memory problems. Caring in this setting can
      be difficult and stressful for care staff who work long hours, have little
      opportunity for training, are poorly paid and yet subject to high expectation.
      This may affect their mental and physical wellbeing, cause high rates of staff
      turnover and absenteeism, and affect the quality of care they provide. The main
      objective of this survey was to explore the nature, characteristics and
      associations of stress in care home staff. METHODS: Staff working in a stratified
      random sample of care homes within Wales completed measures covering: general
      health and wellbeing (SF-12); stress (Work Stress Inventory); job content
      (Karasek Job Content); approach to, and experience of, working with people living
      with dementia (Approaches to Dementia Questionnaire; and Experience of Working
      with Dementia Patients); and Productivity and Health Status (SPS-6). Multiple
      linear regressions explored the effects of home and staff characteristics on
      carers. RESULTS: 212 staff from 72 care homes completed questionnaires. Staff
      from nursing homes experienced more work stress than those from residential homes
      (difference 0.30; 95% confidence interval (CI) from 0.10 to 0.51; P < 0.01), and
      were more likely to report that their health reduced their ability to work
      (difference -4.77; CI -7.80 to -1.73; P < 0.01). Psychological demands on nurses
      were higher than on other staff (difference = 1.57; CI 0.03 to 3.10; P < 0.05). A
      positive approach to dementia was more evident in those trained in dementia care
      (difference 8.54; CI 2.31 to 14.76; P < 0.01), and in staff working in local
      authority homes than in the private sector (difference 7.75; CI 2.56 to 12.94; P
      < 0.01). CONCLUSIONS: Our study highlights the importance of dementia training in
      care homes, with a particular need in the private sector. An effective
      intervention to reduce stress in health and social care staff is required,
      especially in nursing and larger care homes, and for nursing staff. TRIAL
      REGISTRATION: ISRCTN registry: ISRCTN80487202. Registered 24 July 2013.

PMID- 28503091
TI  - Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases.
AB  - DNA topoisomerases are important cellular enzymes found in almost all types of
      living cells (eukaryotic and prokaryotic). These enzymes are essential for
      various DNA metabolic processes e.g. replication, transcription, recombination,
      chromosomal decatenation etc. These enzymes are important molecular drug targets
      and inhibitors of these enzymes are widely used as effective anticancer and
      antibacterial drugs. However, topoisomerase inhibitors have some therapeutic
      limitations and they exert serious side effects during cancer chemotherapy. Thus,
      development of novel anticancer topoisomerase inhibitors is necessary for
      improving cancer chemotherapy. Nature serves as a repertoire of structurally and
      chemically diverse molecules and in the recent years many DNA topoisomerase
      inhibitors have been identified from natural sources. The present review
      discusses anticancer properties and therapeutic importance of eighteen recently
      identified natural topoisomerase inhibitors (from the year 2009 to 2015).
      Structural characteristics of these novel inhibitors provide backbones for
      designing and developing new anticancer drugs.

PMID- 28503096
TI  - Affect recognition among adolescents in therapeutic schools: relationships with
      posttraumatic stress disorder and conduct disorder symptoms.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) and conduct disorder (CD)
      symptoms often co-occur in adolescence, but little is known about whether they
      show common or distinct emotional processing deficits. METHOD: We examined the
      effects of PTSD and CD symptoms on facial affect processing in youth with
      emotional and behavior problems. Teens enrolled in therapeutic day schools (N =
      371; ages 13-19) completed a structured diagnostic assessment and the Diagnostic
      Analysis of Nonverbal Accuracy-2 facial affect recognition task. RESULTS: PTSD
      symptoms were associated with deficits in the recognition of angry facial
      expressions, specifically the false identification of angry faces as fearful. CD
      symptoms were associated with greater difficulty correctly identifying sadness.
      CONCLUSIONS: Findings suggest specificity in the relationships of PTSD and CD
      symptoms with emotional processing.

PMID- 28503097
TI  - Asthma management among allergists in Italy: results from a survey.
AB  - BACKGROUND: In Europe more than 50% of asthmatic treated patients have not well
      controlled asthma. Asthma affects about 2.5 million of patients in Italy. AIMS
      AND OBJECTIVES: The present survey aims at investigating how Italian allergists
      approach asthmatic patients, in order to highlight pitfalls and unmet needs
      concerning real-life asthma management. METHODS: An anonymous 16 item web
      questionnaire was available (April-October 2015) to all allergists who visited
      the web site of SIAAIC (Societa Italiana di Allergologia, Asma Immunologia
      Clinica). Those who wished to give their contribution had the opportunity to
      answer about epidemiology, risk factors, treatment approaches, and adherence to
      therapy. RESULTS: One hundred and seventy four allergists answered the survey.
      54% of them reported up to 10 patient visits per week and 35.3% between 10 and
      30. The most frequent reasons of follow up visits are routine check-up (56.5% of
      allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas,
      gastro-esophageal reflux and obesity are the most important comorbidities/risk
      factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO
      levels and reduced exercise tolerance are the most important indicators of asthma
      severity. Concerning therapy, ICS combined with LABA is the treatment of choice
      suitable for the majority of patients. A rapid onset of action and a flexible ICS
      dosage are indicated as the optimal characteristics for achieving the therapeutic
      goals. Poor adherence to therapy is an important reason for symptom worsening for
      the majority of allergists. Complex dosage regimens and economic aspects are
      considered the most important factors impacting on adherence. CONCLUSIONS:
      Allergists are involved in the management of asthma, regularly seeing their
      patients. Co-morbidities are frequent in asthmatic patients and may impact
      negatively on disease control, thus identifying patients who need a more careful
      and strict monitoring. Airway hyper-responsiveness to methacholine challenge test
      and nitric oxide are considered important indicators of asthma severity. The
      combination of LABA and inhaled steroids is considered the treatment of choice
      for most asthmatic patients, in keeping with broad evidence indicating that the
      combination therapy is more effective and rapid in gaining asthma control than
      inhaled corticosteroids alone. Adherence to medication regimens is considered of
      essence to achieve the therapeutic goals.

PMID- 28503095
TI  - The cholesterol metabolite 27-hydroxycholesterol stimulates cell proliferation
      via ERbeta in prostate cancer cells.
AB  - BACKGROUND: For every six men, one will be diagnosed with prostate cancer (PCa)
      in their lifetime. Estrogen receptors (ERs) are known to play a role in prostate
      carcinogenesis. However, it is unclear whether the estrogenic effects are
      mediated by estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta).
      Although it is speculated that ERalpha is associated with harmful effects on PCa,
      the role of ERbeta in PCa is still ill-defined. The cholesterol oxidized
      metabolite 27-hydroxycholesterol (27-OHC) has been found to bind to ERs and act
      as a selective ER modulator (SERM). Increased 27-OHC levels are found in
      individuals with hypercholesterolemia, a condition that is suggested to be a risk
      factor for PCa. METHODS: In the present study, we determined the extent to which
      27-OHC causes deleterious effects in the non-tumorigenic RWPE-1, the low
      tumorigenic LNCaP, and the highly tumorigenic PC3 prostate cancer cells. We
      conducted cell metabolic activity and proliferation assays using MTS and CyQUANT
      dyes, protein expression analyses via immunoblots and gene expression analyses
      via RT-PCR. Additionally, immunocytochemistry and invasion assays were performed
      to analyze intracellular protein distribution and quantify transepithelial cell
      motility. RESULTS: We found that incubation of LNCaP and PC3 cells with 27-OHC
      significantly increased cell proliferation. We also demonstrate that the ER
      inhibitor ICI 182,780 (fulvestrant) significantly reduced 27-OH-induced cell
      proliferation, indicating the involvement of ERs in proliferation. Interestingly,
      ERbeta levels, and to a lesser extent ERalpha, were significantly increased
      following incubation of PCa cells with 27-OHC. Furthermore, in the presence of
      the ERbeta specific inhibitor, PHTPP, 27-OHC-induced proliferation is attenuated.
      CONCLUSIONS: Altogether, our results show for the first time that 27-OHC, through
      ER activation, triggers deleterious effect in prostate cancer cell lines. We
      propose that dysregulated levels of 27-OHC may trigger or exacerbate prostate
      cancer via acting on ERbeta.

PMID- 28503098
TI  - Absence of 4-1BB reduces obesity-induced atrophic response in skeletal muscle.
AB  - Obesity-induced inflammation causes skeletal muscle atrophy accompanied by
      disruption of oxidative metabolism and is implicated in metabolic complications
      such as insulin resistance and type 2 diabetes. We previously reported that 4
      1BB, a member of the tumor necrosis factor receptor superfamily, participated in
      obesity-induced skeletal muscle inflammation. Here, we show that the absence of 4
      1BB in obese mice fed a high-fat diet led to a decrease in expression of atrophic
      factors (MuRF1 and Atrogin-1) with suppression of NF-kappaB activity, and that
      this was accompanied by increases in mitochondrial oxidative metabolic
      genes/proteins (e.g., PGC-1alpha, CPT1beta, etc.) expression and oxidative muscle
      fibers marker genes/proteins in the skeletal muscle. These findings suggest that
      4-1BB-mediated inflammatory signaling could be a potential target for combating
      obesity-related muscle atrophy and metabolic derangement in skeletal muscle.

PMID- 28503100
TI  - Age and gender considerations for technology-assisted delivery of therapy for
      substance use disorder treatment: A patient survey of access to electronic
      devices.
AB  - BACKGROUND: Technology-assisted treatment (TAT) can be an effective supplement to
      established face-to-face therapy modalities with a growing literature in
      substance use disorder (SUD) treatment. TAT access, interest, and familiarity are
      potential limitations to the use and efficacy of these approaches to treatment.
      METHODS: 174 participants in outpatient SUD treatment were administered a survey
      regarding technology device and Internet access, and interest in engaging in TAT
      SUD counseling (SUDC). The group was dichotomized by mean age and gender to
      examine potential variations in in these subgroups. RESULTS: Forty-three (43%) of
      participants were female, and the mean age was 44.8 years, and 89% of
      participants had Internet access. 83% of participants were interested in TAT for
      SUD counseling; 81% expected it to be at least "moderately helpful." 34% of
      participants noted they would choose to continue face-to-face therapy
      exclusively. 91% of participants had cell phones, but only 50% could access data
      or the Internet via their handheld device. 80% of participants stated they would
      be interested in trying SUDC via their phone. Women had a higher preference for
      computer-based SUDC than men, with gender being significantly correlated with TAT
      perceive helpfulness. CONCLUSION: These findings suggest that patients in
      outpatient SUD treatment have access to resources for TAT implementation,
      although access was not always readily available. Future research will be needed
      to determine whether the technology that this population possesses will be able
      to support the evolving TAT modalities and whether interest in TAT across age and
      gender groups equalizes over time.

PMID- 28503101
TI  - L1-Regularized Least Squares for Support Recovery of High Dimensional Single
      Index Models with Gaussian Designs.
AB  - It is known that for a certain class of single index models (SIMs) [Formula: see
      text], support recovery is impossible when X ~ ??(0, ?? p*p ) and a model
      complexity adjusted sample size is below a critical threshold. Recently, optimal
      algorithms based on Sliced Inverse Regression (SIR) were suggested. These
      algorithms work provably under the assumption that the design X comes from an
      i.i.d. Gaussian distribution. In the present paper we analyze algorithms based on
      covariance screening and least squares with L1 penalization (i.e. LASSO) and
      demonstrate that they can also enjoy optimal (up to a scalar) rescaled sample
      size in terms of support recovery, albeit under slightly different assumptions on
      f and epsilon compared to the SIR based algorithms. Furthermore, we show more
      generally, that LASSO succeeds in recovering the signed support of beta0 if X ~
      ?? (0, Sigma), and the covariance Sigma satisfies the irrepresentable condition.
      Our work extends existing results on the support recovery of LASSO for the linear
      model, to a more general class of SIMs.

PMID- 28503099
TI  - Water deficit mechanisms in perennial shrubs Cerasus humilis leaves revealed by
      physiological and proteomic analyses.
AB  - BACKGROUND: Drought (Water deficit, WD) poses a serious threat to extensively
      economic losses of trees throughout the world. Chinese dwarf cherry (Cerasus
      humilis) is a good perennial plant for studying the physiological and
      sophisticated molecular network under WD. The aim of this study is to identify
      the effect of WD on C. humilis through physiological and global proteomics
      analysis and improve understanding of the WD resistance of plants. METHODS:
      Currently, physiological parameters were applied to investigate C. humilis
      response to WD. Moreover, we used two-dimensional gel electrophoresis (2DE) to
      identify differentially expressed proteins in C. humilis leaves subjected to WD
      (24 d). Furthermore, we also examined the correlation between protein and
      transcript levels. RESULTS: Several physiological parameters, including relative
      water content and Pn were reduced by WD. In addition, the malondialdehyde (MDA),
      relative electrolyte leakage (REL), total soluble sugar, and proline were
      increased in WD-treated C. humilis. Comparative proteomic analysis revealed 46
      protein spots (representing 43 unique proteins) differentially expressed in C.
      humilis leaves under WD. These proteins were mainly involved in photosynthesis,
      ROS scavenging, carbohydrate metabolism, transcription, protein synthesis,
      protein processing, and nitrogen and amino acid metabolisms, respectively.
      CONCLUSIONS: WD promoted the CO2 assimilation by increase light reaction and
      Calvin cycle, leading to the reprogramming of carbon metabolism. Moreover, the
      accumulation of osmolytes (i.e., proline and total soluble sugar) and enhancement
      of ascorbate-glutathione cycle and glutathione peroxidase/glutathione s
      transferase pathway in leaves could minimize oxidative damage of membrane and
      other molecules under WD. Importantly, the regulation role of carbohydrate
      metabolisms (e. g. glycolysis, pentose phosphate pathways, and TCA) was enhanced.
      These findings provide key candidate proteins for genetic improvement of
      perennial plants metabolism under WD.

PMID- 28503102
TI  - Transient Optical and Terahertz Spectroscopy of Nanoscale Films of RuO2.
AB  - Solution-deposited nanoscale films of RuO2 ("nanoskins") are effective
      transparent conductors once calcined to 200  degrees C. Upon heating the
      nanoskins to higher temperature the nanoskins show increased transmission at 550
      nm. Electronic microscopy and X-ray diffraction show that the changes in the
      optical spectrum are accompanied by the formation of rutile RuO2 nanoparticles.
      The mechanism for the spectral evolution is clearly observed with ultrafast
      optical measurements. Following excitation at 400 nm, nanoskins calcined at
      higher temperatures show increased transmission above 650 nm, consistent with the
      photobleaching of a surface-plasmon resonance (SPR) band. Calculations based on
      the optical constants of RuO2 substantiate the presence of SPR absorption. Sheet
      resistance and transient terahertz photoconductivity measurements establish that
      the nanoskins electrically de-wire into separated particles. The plasmonic
      behavior of the nanoskins has implications their use in a range of optical and
      electrochemical applications.

PMID- 28503103
TI  - EDITORIAL: "The Faces of Mania: The Legacy of Athanasios Koukopoulos".

PMID- 28503104
TI  - Introductory considerations Athanasios Koukopoulos: The Man, the Psychiatrist,
      the Original Thinker.

PMID- 28503106
TI  - Depression and Mania in Bipolar Disorder.
AB  - BACKGROUND: Episode duration, recurrence rates, and time spent in manic and
      depressive phases of bipolar disorder (BD) is not well defined for subtypes of
      the disorder. METHODS: We reviewed the course, timing, and duration of episodes
      of mania and depression among 1130 clinically treated DSM-IV-TR BD patients of
      various types, and compared duration and rates as well as total proportion of
      time in depressive versus manic episodes during 16.7 average years at risk.
      RESULTS: As expected, episodes of depressions were much longer than manias, but
      episode-duration did not differ among BD diagnostic types: I, II, with mainly
      mixed-episodes (BD-Mx), or with psychotic features (BD-P). Recurrence rates
      (episodes/year) and proportion of time in depression and their ratios to mania
      were highest in BD-II and BD-Mx subjects, with more manias/year in psychotic and
      BD-I subjects. In most BD-subtypes, except with psychotic features, there was
      more time in depressive than manic morbidity, owing mainly to longer depressive
      than manic episodes. The proportion of time in depression was highest among those
      who followed a predominant DMI course, whereas total time in mania was greatest
      in BD with psychotic features and BD-I. and with an MDI course. CONCLUSIONS:
      Subtypes of BD patients differed little in episode-duration, which was
      consistently much longer for depression. The findings underscore the limited
      control of bipolar depression with available treatments.

PMID- 28503105
TI  - Neurobiological Evidence for the Primacy of Mania Hypothesis.
AB  - BACKGROUND: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM)
      in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi
      and other collaborators. This hypothesis supports that in bipolar disorder, mania
      leads to depression, while depression does not lead to mania. OBJECTIVE: To
      identify evidence in literature that supports or falsifies this hypothesis.
      METHOD: We searched the medical literature (PubMed, Embase, PsycINFO, and the
      Cochrane Library) for peer-reviewed papers on the primacy of mania, the default
      mode function of the brain in normal people and in bipolar disorder patients, and
      on illusion superiority until 6 June, 2016. Papers resulting from searches were
      considered for appropriateness to our objective. We adopted the PRISMA method for
      our review. The search for consistency with PoM was filtered through the
      neurobiological results of superiority illusion studies. RESULTS: Out of a grand
      total of 139 records, 59 were included in our analysis. Of these, 36 were of
      uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was
      contrary, but the latter pooled patients in their manic and depressive phases, so
      to invalidate possible conclusions about its consistency with regard to PoM. All
      considered studies were not focused on PoM or superiority illusion, hence most of
      their results were, as expected, unrelated to the circuitry involved in
      superiority illusion. A considerable amount of evidence is consistent with the
      hypothesis, although indirectly so. LIMITATIONS: Only few studies compared manic
      with depressive phases, with the majority including patients in euthymia.
      CONCLUSION: It is possible that humans have a natural tendency for
      elation/optimism and positive self-consideration, that are more akin to mania;
      the depressive state could be a consequence of frustrated or unsustainable mania.
      This would be consistent with PoM.

PMID- 28503107
TI  - The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in
      522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features.
AB  - OBJECTIVE: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in
      the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with
      drug resistant depression, mania, mixed state and catatonic features. METHOD: 522
      consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT
      course. Responders and nonresponders were compared in subsamples of depressed and
      mixed patients. Descriptive analyses were reported for patients with mania and
      with catatonic features. RESULTS: Of the original sample only 22 patients were
      excluded for the occurrence of side effects or consent withdrawal. After the ECT
      course, 344 (68.8%) patients were considered responders (final CGIi score <=2)
      and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD
      depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic
      features. Length of current episode and global severity of the illness were the
      only statistically significant predictors of nonresponse. CONCLUSION: ECT
      resulted to be an effective and safe treatment for all the phases of severe and
      drug-resistant BD. Positive response was observed in approximately two-thirds of
      the cases and in 80% of the catatonic patients. The duration of the current
      episode was the major predictor of nonresponse. The risk of ECT-induced mania is
      virtually absent and mood destabilization very unlikely. Our results clearly
      indicate that current algorithms for the treatment of depressive, mixed, manic
      and catatonic states should be modified and, at least for the most severe
      patients, ECT should not be considered as a "last resort".

PMID- 28503108
TI  - Diagnosis and Treatment of Cyclothymia: The "Primacy" of Temperament.
AB  - BACKGROUND: Contrary to DSM-5 definition based on recurrence of low grade
      hypomanic and depressive symptoms, cyclothymia is better defined in a
      neurodevelopmental perspective as an exaggeration of cyclothymic temperament.
      Emotional dysregulation with extreme mood instability and reactivity is the core
      features of the complex symptomatology. METHOD: In the present article, we
      critically reviewed the literature on the diagnosis and treatment of cyclothymia,
      focusing on the temperamental and neurodevelopmental perspectives. RESULTS:
      Current epidemiological and clinical research showed the high prevalence and the
      validity of cyclothymia as a distinct form of bipolarity, frequently associated
      with multiple comorbidities with anxiety, impulse control, substance use, and so
      called "personality" disorders. Many patients receive correct diagnosis and
      treatments after many years of illness, when the superposition of complications
      reduces the possibility of complete remission. A therapeutic model combining the
      focus on symptomatic presentations with a temperamental perspective seems to
      represent an effective approach for cyclothymic patients with complex clinical
      presentations. CONCLUSION: Cyclothymic mood instability is an understudied issue
      despite the evidence of its clinical relevance. Unresolved issues concern its
      diagnostic delimitation and the possible relationships with emotional
      dysregulation observed in other neurodevelopmental disorders. We need to confirm
      the specificity of the disorder and to improve its recognition in early phase of
      the life, especially in youth. Early recognition means avoiding unnecessary
      complications and establishing specific treatments and clinical management since
      the beginning.

PMID- 28503109
TI  - Parental Reports of Prodromal Psychopathology in Pediatric Bipolar Disorder.
AB  - OBJECTIVES: Early psychopathology in children diagnosed with Bipolar Disorder
      (BD) remains poorly characterized. Parental retrospective reports provide helpful
      details on the earliest manifestations and their evolution over time. These
      symptoms occur early in the course of BD, often before a formal diagnosis is made
      and/or treatment is implemented, and are of great importance to early recognition
      and prevention. METHODS: Parents of pre-pubertal children and adolescents with
      DSM-IV diagnoses of BD attending an outpatient mood disorders clinic provided
      retrospective ratings of 37 symptoms of child psychopathology. Stability and
      comorbidity of diagnoses were evaluated, and severity of symptoms for each
      subject was assessed by identifying the earliest occurrence of the reported
      symptoms causing impairment. RESULTS: Severe mood instability, temper tantrums,
      anxiety symptoms, sleep disturbances and aggression were among the most common
      signs of psychopathology reported in children diagnosed with BD before puberty.
      Symptoms were already apparent in the first three years in 28%, and formal
      diagnoses were made before the age of 8 y in the majority of cases. CONCLUSIONS:
      Retrospective parental reports of early symptoms of psychopathology in pre
      pubertal children with BD revealed a very early occurrence of affective
      precursors (irritability and mood dysregulation) and clinical risk factors like
      impulsive aggression and anxiety that can precede the syndromal onset of mania by
      several years. These findings support previous reports suggesting a progression
      of symptoms from abnormal, non-specific presentations to sub-threshold and
      finally syndromal BD. The importance of early identification and intervention is
      discussed.

PMID- 28503110
TI  - Pediatric Mania: The Controversy between Euphoria and Irritability.
AB  - Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease,
      consistently associated with family psychiatric history of mood disorders and
      associated with high levels of morbidity and disability and with a great risk of
      suicide. While there is a general consensus on the symptomatology of depression
      in childhood, the phenomenology of pediatric mania is still highly debated and
      the course and long-term outcome of pediatric BD still need to be clarified. We
      reviewed the available studies on the phenomenology of pediatric mania with the
      aim of summarizing the prevalence, demographics, clinical correlates and course
      of these two types of pediatric mania. Eighteen studies reported the number of
      subjects presenting with either irritable or elated mood during mania.
      Irritability has been reported to be the most frequent clinical feature of
      pediatric mania reaching a sensitivity of 95-100% in several samples. Only half
      the studies reviewed reported on number of episodes or cycling patterns and the
      described course was mostly chronic and ultra-rapid whereas the classical
      episodic presentation was less common. Few long-term outcome studies have
      reported a diagnostic stability of mania from childhood to young adult age.
      Future research should focus on the heterogeneity of irritability aiming at
      differentiating distinct subtypes of pediatric psychiatric disorders with
      distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of
      samples attending to mood presentation, irritable versus elated, and course,
      chronic versus episodic, may help clarify whether these are meaningful
      distinctions in the course, treatment and outcome of pediatric onset bipolar
      disorder.

PMID- 28503111
TI  - Free Interval Duration: Clinical Evidence of the Primary Role of Excitement in
      Bipolar Disorder.
AB  - BACKGROUND: Cyclicity is the essential feature of Bipolar disorder, but the
      effect of different cycle patterns on the clinical features is poorly understood.
      Moreover, no studies investigated the relationship between mania and depression
      inside the manic-depressive cycle. OBJECTIVE: The aim of this study is to verify
      the presence of a relationship between the manic and the depressive phase during
      the course of bipolar disorder. METHOD: 160 consecutive patients with BD type I
      were recruited and followed for a mean period of 10 years. During the follow-up
      period, four types of euthymic phases were collected: free intervals present
      between a depressive and a manic/hypomanic episode (D-M); free intervals present
      between a manic/hypomanic and a depressive episode (M-D); free intervals present
      between two depressive episodes (D-D); free intervals present between two
      manic/hypomanic episodes (M-M). One-way ANOVA using the groups as independent
      variable and the duration of the free intervals as dependent variables was used.
      Furthermore, ANOVA was followed by Fisher's Protected Least Significant
      Difference post-hoc test to measure between-group differences. RESULTS: M-D-free
      interval phases were shorter than D-M-free intervals. M-D intervals were the
      shortest ones, the D-D and D-M did not differ, and the M-M were the longest.
      CONCLUSION: The strict temporal link between manic and depressive phases supports
      the idea that the manic-depressive cycle usually begins with a manic episode, and
      that the subsequent depression is often the consequence of subsiding mania.

PMID- 28503112
TI  - Athanasios Koukopoulos' Psychiatry: The Primacy of Mania and the Limits of
      Antidepressants.
AB  - BACKGROUND: Athanasios Koukopoulos provided a radical model for understanding
      depressive and manic conditions. OBJECTIVE: To review, explain, and analyze
      Koukopoulos' concept of the primacy of mania, with special attention to the role
      of antidepressants. METHOD: A conceptual review of Koukopoulos' writings and
      lectures on this topic is given. RESULTS: Koukopoulos held that depressive states
      are caused by manic states; the former do not occur without the latter. The most
      common scenario of the inseparability of depressive and manic symptoms occurs in
      mixed states, which we estimate to represent about one-half of all depressive
      episodes in all patients (not just bipolar illness). In a review of the empirical
      evidence for this topic, we conclude that empirical evidence exists to support
      the primary of mania thesis in almost 80% of depressed patients. Since
      antidepressants worsen mania, they would be expected to worsen depression as well
      in this model. We provide evidence that supports this view in most persons with
      depressive states. CONCLUSION: Koukopoulos' model of affective illness is one
      where manic states are the primary pathology, and depressive conditions are a
      secondary consequence. Hence treatment of depression with antidepressants would
      be less effective than treatment with mood stabilizers, since treating an effect
      is less successful than treating its cause. This approach would reverse current
      assumptions in psychiatry.

PMID- 28503113
TI  - Who's the Leader, Mania or Depression? Predominant Polarity and
      Alcohol/Polysubstance Use in Bipolar Disorders.
AB  - BACKGROUND: Predominant polarity characterises patients who mainly manifest
      recurrences of depression or mania/hypomania. Alcohol use disorder (AUD) and
      polysubstance use (PSU), which often complicate bipolar disorder (BD) and affect
      its clinical course, can influence predominant polarity. Nevertheless, previous
      studies have not clarified if BD patients differ in predominant polarity from BD
      patients with substance use disorder (SUD) comorbidity. OBJECTIVE: The aim of
      this study was to compare predominant polarity between BD without SUD, BD with
      AUD and BD with PSU. We also investigated the association between predominant
      polarity and first episode polarity in each diagnostic group. METHOD: We
      evaluated predominant polarity (>=2:1 lifetime depressive vs. manic/hypomanic
      episodes) in 218 DSM-IV-TR BD patients. Specifically, data were obtained from 86
      patients with BD without SUD, 69 patients with BD and AUD, and 63 patients with
      BD and PSU with alcohol as the primary substance abused. RESULTS: The three
      groups significantly differed for predominant polarity. The most common
      predominant polarity in BD without SUD was manic, while in BD with AUD and in BD
      with PSU it was depressive. Uncertain predominant polarity was the least common
      in BD without SUD and BD with PSU, whereas in BD with AUD, manic predominant
      polarity was least common. Predominant polarity matched onset polarity in all
      groups. CONCLUSION: BD without SUD, BD with AUD, and BD with PSU have different
      predominant polarities. The correspondence between predominant polarity and
      polarity at the onset may impact diagnosis and treatment of BD.

PMID- 28503114
TI  - Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of
      Manic-Depressive Illness.
AB  - BACKGROUND: Mania seems to be associated with an increased dopamine (DA)
      transmission. Antidepressant treatments can induce mania in humans and
      potentiated DA transmission in animals, by sensitizing DA D2 receptors in the
      mesolimbic system. We have suggested that the sensitization of D2 receptors may
      be responsible of antidepressant-induced mania. This review aims to report the
      experimental evidence that led to the hypothesis that antidepressant-induced DA
      receptors dysregulation can be considered an animal model of bipolar disorder.
      METHODS: We reviewed papers reporting preclinical and clinical studies on the
      role of DA in the mechanism of action of antidepressant treatments and in the
      patho-physiology of mood disorders. RESULTS: A number of preclinical and clinical
      evidence suggests that mania could be associated with an increased DA activity,
      while a reduced function of this neurotransmission might underlie depression.
      Chronic treatment with imipramine induces a sensitization of DA D2 receptors in
      the mesolimbic system, followed, after drug discontinuation, by a reduced
      sensitivity associated with an increased immobility time in forced swimming test
      of depression (FST). Blockade of glutamate NMDA receptors by memantine
      administration prevents the imipramine effect on DA receptors sensitivity and on
      the FST. CONCLUSION: We suggest that chronic treatment with antidepressants
      induces a behavioural syndrome that mimics mania (the sensitization of DA
      receptors), followed by depression (desensitization of DA receptors and increased
      immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover
      the observation that memantine prevents the "bipolar-like" behavior, suggests
      that the drug may have an antimanic and mood stabilizing effect. Preliminary
      clinical observations support this hypothesis.

PMID- 28503115
TI  - Is Mania the Hypertension of the Mood? Discussion of A Hypothesis.
AB  - Beyond both being biphasic/bidirectional disorders (hypo)mania and essential
      hypertension share a surprising number of similarities and an overlap between
      their genetics, biological background, underlying personality and temperamental
      factors, precipitating factors, comorbidity and response to treatment, indicating
      a possibly partially shared biological background. Based on theoretical
      knowledge, similarities related to characteristics, manifestation and course, and
      the results of pharmacological studies related to the effects and side effects of
      pharmacotherapies used in the treatment of these two distinct disorders, the
      authors outline a hypothesis discussing the similar origins of these two
      phenomena and thus mania being the hypertension of mood in memory of Athanasios
      Koukopoulos, one of the greatest researchers and theoreticists of mania of all
      time.

PMID- 28503118
TI  - An Additional Method for Analyzing the Reversible Inhibition of an ?Enzyme Using
      Acid Phosphatase as a Model.
AB  - Using wheat germ acid phosphatase and sodium orthovanadate as a competitive
      inhibitor, a novel method for analyzing reversible inhibition was carried out.
      Our alternative approach involves plotting the initial velocity at which product
      is formed as a function of the ratio of substrate concentration to inhibitor
      concentration at a constant enzyme concentration and constant assay conditions.
      The concept of initial concentrations driving equilibrium leads to the chosen
      axes. Three apparent constants can be derived from this plot: Kmax, Kmin, and
      Kinflect. Kmax and Kmin represent the substrate to inhibitor concentration ratio
      for complete inhibition and minimal inhibition, respectively. Kinflect represents
      the substrate to inhibitor concentration ratio at which the enzyme-substrate
      complex is equal to the inhibitory complex. These constants can be interpolated
      from the graph or calculated using the first and second derivative of the plot.
      We conclude that a steeper slope and a shift of the line to the right (increased
      x-axis values) would indicate a better inhibitor. Since initial velocity is not a
      linear function of the substrate/inhibitor ratio, this means that inhibition
      changes more quickly with the change in the [S]/ [I] ratio. When preincubating
      the enzyme with substrate before the addition of inhibitor, preincubating the
      enzyme with inhibitor before the addition of substrate or with concurrent
      addition of both substrate and inhibitor, modest changes in the slopes and y
      intercepts were obtained. This plot appears useful for known competitive and non
      competitive inhibitors and may have general applicability.

PMID- 28503119
TI  - Targeting HIV-1 Envelope Proteins Using a Fragment Discovery All-Atom
      Computational Algorithm.
AB  - INTRODUCTION: HIV viral envelope proteins are targets for small inhibitor
      molecules aimed at disrupting the cellular entry process. Potential peptide-class
      inhibitor molecules (rDNA drugs) have been previously identified, with mixed
      results, through biomimicry and phage display experimental methods. Here we
      describe a new approach based on computational fragment discovery. The method has
      the potential to not only optimize peptide binding affinity but also to rapidly
      produce alternative inhibitors against mutated strains. METHODS: A comprehensive,
      all-atom implicit solvent method is used to bombard the C-heptad repeat unit of
      HIV-1 target envelope protein GP41 with single D-amino acid residues as they
      exist in their native state. A nascent peptide computational search process then
      identifies potential favorable sequences of attached ligands based on four
      peptide bond criteria. Finally, dynamic simulations of nascent peptides attached
      to host targets help refine potential peptide inhibitors for experimental HIV-1
      challenge assays and testing. RESULTS AND DISCUSSION: Initial testing of the
      method was done using 64,000 total ligands of D-amino acid residues at a total
      computational time of 0.05 microseconds per ligand, which resulted in several
      thousand attached ligands. Peptide bond criteria search employing three of the
      four bond constraints with a tolerance of 20 percent, resulted in four potential
      peptide inhibitors of 5 to 6 residues in length. Only one of the four peptides
      demonstrated IC50 values and partial viral inhibition based on cell challenge
      assays using CEM-SS host cells. That peptide inhibitor also computationally
      demonstrated long-time attachment and stability to a helical groove in its C
      heptad target. This initial testing of peptide fragment discovery against HIV-1
      has helped us refine the protocols and identify key areas of improvement.
      CONCLUSION: Our methods demonstrate the potential to design efficient peptide
      inhibitors to viral target proteins based on an all-atom dynamic simulation and
      using a ligand library as fragments of potential nascent peptides. Our methods
      can be greatly improved through the use of higher numbers of ligands, increased
      time of bombardment, and tighter constraints on the peptide bond search step. Our
      method may be important in the need to rapidly respond to target mutations and to
      advance multiple targeting methods based multiple peptide inhibitors.

PMID- 28503121
TI  - Hemostasis and Hemotherapy.

PMID- 28503116
TI  - Melatonin: Pharmacology, Functions and Therapeutic Benefits.
AB  - BACKGROUND: Melatonin synchronizes central but also peripheral oscillators (fetal
      adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing
      temporal organization of biological functions through circadian rhythms (24-hour
      cycles) in relation to periodic environmental changes and therefore adaptation of
      the individual to his/her internal and external environment. Measures of
      melatonin are considered the best peripheral indices of human circadian timing
      based on an internal 24-hour clock. METHODS: First, the pharmacology of melatonin
      (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action)
      is described, allowing a better understanding of the short and long term effects
      of melatonin following its immediate or prolonged release. Then, research related
      to the physiological effects of melatonin is reviewed. RESULTS: The physiological
      effects of melatonin are various and include detoxification of free radicals and
      antioxidant actions, bone formation and protection, reproduction, and
      cardiovascular, immune or body mass regulation. Also, protective and therapeutic
      effects of melatonin are reported, especially with regard to brain or
      gastrointestinal protection, psychiatric disorders, cardiovascular diseases and
      oncostatic effects. CONCLUSION: This review highlights the high number and
      diversity of major melatonin effects and opens important perspectives for
      measuring melatonin as a biomarker (biomarker of early identification of certain
      disorders and also biomarker of their follow-up) and using melatonin with
      clinical preventive and therapeutic applications in newborns, children and adults
      based on its physiological regulatory effects.

PMID- 28503120
TI  - A two-week pilot study of intranasal oxytocin for cocaine-dependent individuals
      receiving methadone maintenance treatment for opioid use disorder.
AB  - 30-60% of patients receiving methadone for opioid use disorder (OUD) actively use
      cocaine. Cocaine use disorder (CUD) has no FDA-approved pharmacological
      treatment; existing psychosocial treatments are inadequate. Oxytocin, a social
      neuropeptide, has preclinical promise as an adjunctive treatment for both OUD and
      CUD. Twenty-two individuals receiving methadone for OUD with co-occurring CUD
      were randomized to receive oxytocin or placebo intranasally 40 IU twice daily for
      two weeks. A priori aims were feasibility and safety. Exploratory effectiveness
      aims included laboratory-based measures of drug craving, drug-related implicit
      cognition, and drug use. High retention rates (93.5%), the absence of study
      related adverse events, and the fact that oxytocin was well tolerated in this
      population support the feasibility of larger trials. Two weeks of oxytocin (but
      not placebo) significantly reduced cocaine craving at day 15 compared to baseline
      (mean change+/-SD: OT=-0.23+/-0.19, p=0.004; PL=-0.16+/-0.29, p=0.114). For
      heroin craving, the placebo group reported a trend-level increase over time while
      the oxytocin group remained unchanged - with medium to large effect sizes between
      the groups (Cohen's d=0.71-0.90). Oxytocin led to a significant switch from
      implicit self-association with drugs to implicitly associating drugs with others
      (mean change+/-SD: 0.25+/-0.35, p=0.037) and a trend-level reduction in self
      reported cocaine use over time (Z=-1.78, p=0.075). Furthermore, oxytocin
      significantly increased the accuracy of self-reported cocaine use when correlated
      with quantitative urine levels of cocaine metabolite. This proof-of-concept study
      provides promising early evidence that oxytocin may be an effective adjunct to
      the treatment of co-occurring CUD and OUD. Further investigation with larger
      trials is warranted.

PMID- 28503117
TI  - Opioids Resistance in Chronic Pain Management.
AB  - Chronic pain management represents a serious healthcare problem worldwide.
      Chronic pain affects approximately 20% of the adult European population and is
      more frequent in women and older people. Unfortunately, its management in the
      community remains generally unsatisfactory and rarely under the control of
      currently available analgesics. Opioids have been used as analgesics for a long
      history and are among the most used drugs; however, while there is no debate over
      their short term use for pain management, limited evidence supports their
      efficacy of long-term treatment for chronic non-cancer pain. Therapy with opioids
      is hampered by inter-individual variability and serious side effects and some
      opioids often result ineffective in the treatment of chronic pain and their use
      is controversial. Accordingly, for a better control of chronic pain a deeper
      knowledge of the molecular mechanisms underlying resistance to opiates is
      mandatory.

PMID- 28503122
TI  - Thrombosis in Inherited Fibrinogen Disorders.
AB  - Although inherited fibrinogen disorders (IFD) are primarily considered to be
      bleeding disorders, they are associated with a higher thrombotic complication
      risk than defects in other clotting factors. Managing IFD patients with
      thrombosis is challenging as anticoagulant treatment may exacerbate the
      underlying bleeding risk which can be life-threatening. Due to the low prevalence
      of IFD, there is little information on pathophysiology or optimal treatment of
      thrombosis in these patients. We searched the literature for cases of thrombosis
      among IFD patients and identified a total of 128 patient reports. In
      approximately half of the cases, thromboses were spontaneous, while in the others
      trauma, surgery, and parturition contributed to the risk. The true mechanism(s)
      of thrombosis in IFD patients remain to be elucidated. A variety of anticoagulant
      treatments have been used in the treatment or prevention of thrombosis, sometimes
      with concurrent fibrinogen replacement therapy. There is no definite evidence
      that fibrinogen supplementation increases the risk of thrombosis, and it may
      potentially be effective in the treatment and prevention of both thrombosis and
      hemorrhage in IFD patients.

PMID- 28503123
TI  - Thromboelastometry and Thrombelastography Analysis under Normal Physiological
      Conditions - Systematic Review.
AB  - BACKGROUND: Studies investigating thromboelastometry or thrombelastography
      analyses in a physiological context are scattered and not easy to access.
      OBJECTIVE: To systematically retrieve and describe published reports studying
      healthy subjects and targeting at the correlation of ROTEM(r) and TEG(r)
      measurements with conventional parameters of hemostasis. METHODS: Systematic
      Review: Papers were searched in Medline, Scopus and the Science Citation Index
      database. Reference lists of included studies and of reviews were screened. To be
      included papers had to report ROTEM or TEG data on healthy subjects. Two
      reviewers screened papers for inclusion, read full texts of potentially relevant
      papers, and extracted data of included papers. RESULTS: Searches identified 1,721
      records of which 1,713 were either excluded immediately or after reading the full
      text. The remaining 8 studies enrolled 632 subjects. The association of
      conventional parameters of hemostasis with ROTEM and with TEG was investigated in
      one and two studies, respectively. Overall correlation was limited and ranged
      from 0.0 to 0.40 (total thrombus generation vs. fibrinogen; clotting time INTEM
      vs. activated partial thromboplastin time). CONCLUSIONS: Studies assessing the
      relationship between thromboelastometry or thromboelastography analyses and
      conventional parameters of hemostasis in healthy subjects remains scarce, and
      correlations are limited. Further research is needed to understand the physiology
      of thromboelastometry and thromboelastography parameters.

PMID- 28503125
TI  - Thawing of Pooled, Solvent/Detergent-Treated Plasma octaplasLG(r): Validation
      Studies Using Different Thawing Devices.
AB  - BACKGROUND: The aim of this study was to perform validation of the thawing
      process for solvent/detergent-treated plasma octaplasLG(r) using different
      thawing devices. Optimized settings for temperature and thawing time should be
      defined based on the results of both temperature measurements and extensive
      biochemical characterization studies. METHODS: octaplasLG units were thawed using
      water bath systems (i.e. MB-13A, QuickThaw(r) DH4), dry tempering systems (i.e.
      plasmatherm, SAHARA-III), and microwave oven (i.e. transfusio-therm(r) 2000).
      Optimized thawing conditions were defined. Subsequently, using the selected
      thawing conditions, octaplasLG units were thawed and tested on product release
      parameters. RESULTS: The fastest thawing was observed for the microwave oven. All
      octaplasLG units thawed by different devices and optimized thawing conditions
      were clear and free of solid and gelatinous particles, indicating no protein
      denaturation or overheating. In addition, no significant differences were found
      in the coagulation and inhibition activity and hemostatic potency of octaplasLG
      when thawed by the different devices tested. All parameters after thawing were
      within the product release specification levels. CONCLUSION: Our study
      demonstrated that octaplasLG can be thawed using all above listed devices without
      any negative influence on the plasma quality, presupposed that optimized settings
      defined for this plasma product are used.

PMID- 28503126
TI  - In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a
      New Ecarin-Based Thromboelastometry Test.
AB  - BACKGROUND: An increasing number of oral anticoagulants has been approved,
      including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that
      requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the
      diluted thrombin time measured with Hemoclot(r) has shown reliable results. So
      far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM
      assay uses ecarin to initiate the coagulation cascade at the step of thrombin
      generation and measures the clotting time (CT) by thromboelastometry. METHODS:
      This study investigated the correlation of the EcaTEM with standard laboratory
      assays in dabigatran-treated patients. Ten patients undergoing total hip or knee
      arthroplasty were included in the study. DE for thromboprophylaxis was started 4
      h after surgery. Blood samples were taken before surgery as well as 2, 6 and 12 h
      after ingestion on the 3rd postoperative day. Dabigatran concentration
      (Hemoclot), activated partial thromboplastin time, thrombin time and CT EcaTEM
      were measured. RESULTS: Only CT EcaTEM and Hemoclot showed a correlation > 0.75
      for all measurements. CONCLUSION: CT EcaTEM appears a valid PoC method parameter
      to detect thrombin inhibition and thus the presence of dabigatran beside diluted
      thrombin time at different concentration levels. This may represent an
      opportunity to identify the presence of dabigatran, e.g., in emergency
      situations.

PMID- 28503124
TI  - Factor XIII Deficiency and Thrombocytopenia Are Frequent Modulators of
      Postoperative Clot Firmness in a Surgical Intensive Care Unit.
AB  - OBJECTIVE: Fibrinogen and factor XIII (FXIII) have been shown to critically
      influence clot firmness in the intraoperative setting and thus likely influence
      intraoperative bleeding. We were interested to identify potential modulators of
      postoperative clot firmness in a tertiary care hospital surgical intensive care
      unit setting, independent of their clinical course during surgery. METHODS: 272
      day-shift consecutive patients were evaluated for whole blood clot firmness
      evaluated by the ROTEM(r) EXTEM thrombelastometric assay and various potential
      modulators of clot firmness upon arrival at the surgical intensive care unit
      (SICU). RESULTS: Maximum clot firmness on the SICU was found to be independently
      influenced by the amount of colloids given during surgery as well as by platelet
      count, fibrinogen concentration, and FXIII activity at the time of SICU
      admission. In patients with lowest clot firmness, FXIII activity was the most
      important independent modulator of clot firmness; in patients with the highest
      clot firmness, platelet count and fibrinogen concentration were the most
      important modulators of clot firmness. Deficiencies (i.e., results below normal
      range) of these modulators of clot firmness were most prevalent for FXIII
      (activity < 70%: 45% of cases), which was significantly more frequent than
      thrombocytopenia (<150 * 109/l: 32%) or fibrinogen deficiency (<1.5 g/l: 6%).
      CONCLUSIONS: Postoperative clot firmness as evaluated by whole blood
      thrombelastometry (ROTEM EXTEM assay) is independently and frequently modulated
      though FXIII activity and the platelet count, while fibrinogen concentration is
      also an independent but much less frequent modulator. Different modulators show
      different influences, depending on the clot firmness being present. Colloids
      infused during surgery also independently modulate postoperative clot firmness.
      Based on our data, strategies can be developed to improving postoperative care of
      patients with bleedings or at risk for bleeding.

PMID- 28503127
TI  - The Role of Platelet Function Analyzer Testing in Cardiac Surgery Transfusion
      Management.
AB  - BACKGROUND: Identifying high-risk patients for transfusion after cardiac
      operations would alter postoperative management. The aim of this study was to
      investigate closure time (CT) measured by platelet function analyzer (PFA) for
      prediction of bleeding and transfusions. METHODS: 66 patients were scheduled for
      coronary artery bypass graft (CABG) surgery and 30 patients for valve repair and
      replacement (non-CABG). Measurements of PFA-100(r) CT for collagen and adenosine
      diphosphate (cADP) and collagen and epinephrine (cEPI) were performed 15 min
      after protamine administration. Blood loss was measured, and the amount of
      transfusion products was recorded postoperatively. RESULTS: The study
      demonstrated significant differences between CABG patients with cADP-CT >= 118 s
      and those with cADP-CT < 118 s with regard to blood loss for 24 h (p = 0.001) and
      blood loss for 25-48 h (p = 0.003) as well as fresh frozen plasma (p = 0.015),
      platelet (p > 0.001) and red blood cell (p = 0.002) units given in 48
      postoperative h. There were no differences cardiopulmonary bypass when was
      applied. In non-CABG patients, there were no differences in blood loss and
      transfusion requirements with respect to cADP-CT and cEPI-CT. CONCLUSION:
      Postoperative platelet dysfunction measured by a prolonged cADP-CT was
      significant predictor of blood loss and transfusion in CABG patients.

PMID- 28503128
TI  - A Confounding Case of Inherited Factor V Deficiency Complicated by Inhibitors at
      First Presentation.
AB  - INTRODUCTION: Inherited factor V deficiency / Owren's disease has varied clinical
      manifestations ranging from asymptomatic laboratory abnormalities to massive
      hemorrhage. The acquired form due to inhibitors following antibiotic therapy,
      infection, or surgery is less common, and spontaneous development of inhibitors
      is not known. CASE REPORT: An 18-year-old boy presented with bleeding axillary
      and groin ulcers. At the age of 15, due to recurrent epistaxis and gum bleed, he
      was diagnosed with acquired factor V deficiency with positive inhibitor screen
      and treated with fresh frozen plasma (FFP) transfusion and temporary
      azathioprine. Coagulation workup at his current presentation also revealed
      acquired factor V deficiency with presence of inhibitors. The tests were repeated
      after 6 weeks of intermittent FFP transfusion, and the differences observed
      included negative inhibitor screen and complete correction on mixing studies, but
      factor V level was 2%. DISCUSSION: Evidence of inhibitors at presentation favored
      acquired disease. However, younger age of onset, detection of inhibitors 1 year
      after first episode of self-regressing bleed, lack of identifiable triggers, and
      persistent bleeding with reduced factor levels after disappearance of inhibitors
      favored inherited factor V deficiency. CONCLUSION: In this case report, we have
      described an interesting case of severe inherited factor V deficiency with
      spontaneous appearance and disappearance of inhibitors exhibiting nonspecific
      factor inhibitory activity.

PMID- 28503129
TI  - Pathophysiology, Diagnosis and Treatment of Somatosensory Tinnitus: A Scoping
      Review.
AB  - Somatosensory tinnitus is a generally agreed subtype of tinnitus that is
      associated with activation of the somatosensory, somatomotor, and visual-motor
      systems. A key characteristic of somatosensory tinnitus is that is modulated by
      physical contact or movement. Although it seems common, its pathophysiology,
      assessment and treatment are not well defined. We present a scoping review on the
      pathophysiology, diagnosis, and treatment of somatosensory tinnitus, and identify
      priority directions for further research. Methods: Literature searches were
      conducted in Google Scholar, PubMed, and EMBASE databases. Additional broad hand
      searches were conducted with the additional terms etiology, diagnose, treatment.
      Results: Most evidence on the pathophysiology of somatosensory tinnitus suggests
      that somatic modulations are the result of altered or cross-modal synaptic
      activity within the dorsal cochlear nucleus or between the auditory nervous
      system and other sensory subsystems of central nervous system (e.g., visual or
      tactile). Presentations of somatosensory tinnitus are varied and evidence for the
      various approaches to treatment promising but limited. Discussion and
      Conclusions: Despite the apparent prevalence of somatosensory tinnitus its
      underlying neural processes are still not well understood. Necessary involvement
      of multidisciplinary teams in its diagnosis and treatment has led to a large
      heterogeneity of approaches whereby tinnitus improvement is often only a
      secondary effect. Hence there are no evidence-based clinical guidelines, and
      patient care is empirical rather than research-evidence-based. Somatic testing
      should receive further attention considering the breath of evidence on the
      ability of patients to modulate their tinnitus through manouvers. Specific
      questions for further research and review are indicated.

PMID- 28503131
TI  - Editorial: Myelin-Mediated Inhibition of Axonal Regeneration: Past, Present, and
      Future.

PMID- 28503130
TI  - Uncoupling the Trade-Off between Somatic Proteostasis and Reproduction in
      Caenorhabditis elegans Models of Polyglutamine Diseases.
AB  - Caenorhabditis elegans somatic protein homeostasis (proteostasis) is actively
      remodeled at the onset of reproduction. This proteostatic collapse is regulated
      cell-nonautonomously by signals from the reproductive system that transmit the
      commitment to reproduction to somatic cells. Here, we asked whether the link
      between the reproductive system and somatic proteostasis could be uncoupled by
      activating downstream effectors in the gonadal longevity cascade. Specifically,
      we examined whether over-expression of lipl-4 (lipl-4(oe)), a target gene of the
      gonadal longevity pathway, or increase in arachidonic acid (AA) levels,
      associated with lipl-4(oe), modulated proteostasis and reproduction. We found
      that lipl-4(oe) rescued somatic proteostasis and postponed the onset of
      aggregation and toxicity in C. elegans models of polyglutamine (polyQ) diseases.
      However, lipl-4(oe) also disrupted fatty acid transport into developing oocytes
      and reduced reproductive success. In contrast, diet supplementation of AA
      recapitulated lipl-4(oe)-mediated proteostasis enhancement in wild type animals
      but did not affect the reproductive system. Thus, the gonadal longevity pathway
      mediates a trade-off between somatic maintenance and reproduction, in part by
      regulating the expression of genes, such as lipl-4, with inverse effects on
      somatic maintenance and reproduction. We propose that AA could uncouple such
      germline to soma crosstalk, with beneficial implications protein misfolding
      diseases.

PMID- 28503132
TI  - Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing
      Phenoxybenzamine's Potential.
AB  - Aminoglycosides (AGs) are widely used antibiotics because of their low cost and
      high efficacy against gram-negative bacterial infection. However, AGs are
      ototoxic, causing the death of sensory hair cells in the inner ear. Strategies
      aimed at developing or discovering agents that protect against aminoglycoside
      ototoxicity have focused on inhibiting apoptosis or more recently, on preventing
      antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds
      using the larval zebrafish lateral line identified phenoxybenzamine as a
      potential protectant for aminoglycoside-induced hair cell death. Here we used
      live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with
      hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian
      cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic
      neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian
      hair cells in a reversible and dose-dependent manner, but pre-incubation is
      required for maximal inhibition of entry. We observed differential effects of
      phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair
      cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The
      requirement for pre-incubation and reversibility suggests an intracellular rather
      than an extracellular site of action for phenoxybenzamine. We also tested the
      efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear
      explants the hair cell death resulting from 24 h exposure to neomycin was steeply
      dose-dependent, with 50% cell death occurring at ~230 MUM for both IHC and OHC.
      We used 250 MUM neomycin in subsequent hair-cell death assays. At 100 MUM with 1
      h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs
      and OHCs, however at higher concentrations phenoxybenzamine itself showed clear
      signs of ototoxicity and an additive toxic effect when combined with neomycin.
      These data do not support the use of phenoxybenzamine as a therapeutic agent in
      mammalian inner ear. Our findings do share parallels with the observations from
      the zebrafish lateral line model but they also highlight the necessity for
      validation in the mammalian system and the potential for differential effects on
      sensory hair cells from different species, in different systems and even between
      cells in the same organ.

PMID- 28503133
TI  - Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain
      Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy
      in Drosophila.
AB  - The lifespan of Drosophilamelanogaster can be extended substantially by inducing
      reproductive dormancy (also known as diapause) by lowered temperature and short
      days. This increase of longevity is accompanied by lowered metabolism and
      increased stress tolerance. We ask here whether behavioral senescence is
      ameliorated during adult dormancy. To study this we kept flies for seven or more
      weeks in normal rearing conditions or in diapause conditions and compared to 1
      week-old flies in different behavioral assays of sleep, negative geotaxis and
      exploratory walking. We found that the senescence of geotaxis and locomotor
      behavior seen under normal rearing conditions was negligible in flies kept in
      dormancy. The normal senescence of rhythmic activity and sleep patterns during
      the daytime was also reduced by adult dormancy. Investigating the morphology of
      specific neuromuscular junctions (NMJs), we found that changes normally seen with
      aging do not take place in dormant flies. To monitor age-associated changes in
      neuronal circuits regulating activity rhythms, sleep and walking behavior we
      applied antisera to tyrosine hydroxylase (TH), serotonin and several
      neuropeptides to examine changes in expression levels and neuron morphology. In
      most neuron types the levels of stored neuromodulators decreased during normal
      aging, but not in diapause treated flies. No signs of neurodegeneration were seen
      in either condition. Our data suggest that age-related changes in motor neurons
      could be the cause of part of the behavioral senescence and that this is
      ameliorated by reproductive diapause. Earlier studies established a link between
      age-associated decreases in neuromodulator levels and behavioral decline that
      could be rescued by overexpression of neuromodulator. Thus, it is likely that the
      retained levels of neuromodulators in dormant flies alleviate behavioral
      senescence.

PMID- 28503134
TI  - Aquaporin 4-Mediated Glutamate-Induced Astrocyte Swelling Is Partially Mediated
      through Metabotropic Glutamate Receptor 5 Activation.
AB  - Astrocytes are one of the most abundant cell types in the mammalian central
      nervous system (CNS), and astrocyte swelling is the primary event associated with
      brain edema. Glutamate, the principal excitatory amino acid neurotransmitter in
      the CNS, is released at high levels after brain injury including cerebral
      ischemia. This leads to astrocyte swelling, which we previously demonstrated is
      related to metabotropic glutamate receptor (mGluR) activation. Aquaporin 4
      (AQP4), the predominant water channel in the brain, is expressed in astrocyte
      endfeet and plays an important role in brain edema following ischemia. Studies
      recently showed that mGluR5 is also expressed on astrocytes. Therefore, it is
      worth investigating whether AQP4 mediates the glutamate-induced swelling of
      astrocytes via mGluR5. In the present study, we found that 1 mM glutamate induced
      astrocyte swelling, quantified by the cell perimeter, but it had no effect on
      astrocyte viability measured by the cell counting kit-8 (CCK-8) and lactate
      dehydrogenase (LDH) assays. Quantitative reverse transcription polymerase chain
      reaction analyses revealed that AQP4, among AQP1, 4, 5, 9 and 11, was the main
      molecular expressed in cultured astrocytes. Glutamate-induced cell swelling was
      accompanied by a concentration-dependent change in AQP4 expression. Furthermore,
      RNAi technology revealed that AQP4 gene silencing inhibited glutamate-induced
      astrocyte swelling. Moreover, we found that mGluR5 expression was greatest among
      the mGluRs in cultured astrocytes and was co-expressed with AQP4. Activation of
      mGluR5 in cultured astrocytes using (S)-3,5-dihydroxyphenylglycine (DHPG), an
      mGluR5 agonist, mimicked the effect of glutamate. This effect was abolished by co
      incubation with the mGluR5 antagonist fenobam but was not influenced by DL-threo
      beta-benzyloxyaspartic acid (DL-TBOA), a glutamate transporter inhibitor.
      Finally, experiments in a rat model of transient middle cerebral artery occlusion
      (tMCAO) revealed that co-expression of mGluR5 and AQP4 was increased in astrocyte
      endfeet around capillaries in the penumbra, and this was accompanied by brain
      edema. Collectively, these results suggest that glutamate induces cell swelling
      and alters AQP4 expression in astrocytes via mGluR5 activation, which may provide
      a novel approach for the treatment of edema following brain injury.

PMID- 28503136
TI  - A Quantitative Golgi Study of Dendritic Morphology in the Mice Striatal Medium
      Spiny Neurons.
AB  - In this study we have provided a detailed quantitative morphological analysis of
      medium spiny neurons (MSNs) in the mice dorsal striatum and determined the
      consistency of values among three groups of animals obtained in different set of
      experiments. Dendritic trees of 162 Golgi Cox (FD Rapid GolgiStain Kit)
      impregnated MSNs from 15 adult C57BL/6 mice were 3-dimensionally reconstructed
      using Neurolucida software, and parameters of dendritic morphology have been
      compared among experimental groups. The parameters of length and branching
      pattern did not show statistically significant difference and were highly
      consistent among groups. The average neuronal soma surface was between 160 MUm2
      and 180 MUm2, and the cells had 5-6 primary dendrites with close to 40 segments
      per neuron. Sholl analysis confirmed regular pattern of dendritic branching. The
      total length of dendrites was around 2100 MUm with the average length of
      individual branching (intermediate) segment around 22 MUm and for the terminal
      segment around 100 MUm. Even though each experimental group underwent the same
      strictly defined protocol in tissue preparation and Golgi staining, we found
      inconsistency in dendritic volume and soma surface. These changes could be
      methodologically influenced during the Golgi procedure, although without
      affecting the dendritic length and tree complexity. Since the neuronal activity
      affects the dendritic thickness, it could not be excluded that observed volume
      inconsistency was related with functional states of neurons prior to animal
      sacrifice. Comprehensive analyses of tree complexity and dendritic length
      provided here could serve as an additional tool for understanding morphological
      variability in the most numerous neuronal population of the striatum. As
      reference values they could provide basic ground for comparisons with the results
      obtained in studies that use various models of genetically modified mice in
      explaining different pathological conditions that involve MSNs.

PMID- 28503135
TI  - The Gut Microbiota and Autism Spectrum Disorders.
AB  - Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism
      spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies
      have shown alterations in the composition of the fecal flora and metabolic
      products of the gut microbiome in patients with ASD. The gut microbiota
      influences brain development and behaviors through the neuroendocrine,
      neuroimmune and autonomic nervous systems. In addition, an abnormal gut
      microbiota is associated with several diseases, such as inflammatory bowel
      disease (IBD), ASD and mood disorders. Here, we review the bidirectional
      interactions between the central nervous system and the gastrointestinal tract
      (brain-gut axis) and the role of the gut microbiota in the central nervous system
      (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective
      treatment for ASD.

PMID- 28503139
TI  - A Pilot Study on the Effects of Transcranial Direct Current Stimulation on Brain
      Rhythms and Entropy during Self-Paced Finger Movement using the Epoc Helmet.
AB  - Transcranial direct current stimulation (tDCS) of the cerebellum is emerging as a
      novel non-invasive tool to modulate the activity of the cerebellar circuitry. In
      a single blinded study, we applied anodal tDCS (atDCS) of the cerebellum to
      assess its effects on brain entropy and brain rhythms during self-paced
      sequential finger movements in a group of healthy volunteers. Although wearable
      electroencephalogram (EEG) systems cannot compete with traditional
      clinical/laboratory set-ups in terms of accuracy and channel density, they have
      now reached a sufficient maturity to envision daily life applications. Therefore,
      the EEG was recorded with a comfortable and easy to wear 14 channels wireless
      helmet (Epoc headset; electrode location was based on the 10-20 system).
      Cerebellar neurostimulation modified brain rhythmicity with a decrease in the
      delta band (electrode F3 and T8, p < 0.05). By contrast, our study did not show
      any significant change in entropy ratios and laterality coefficients (LC) after
      atDCS of the cerebellum in the 14 channels. The cerebellum is heavily connected
      with the cerebral cortex including the frontal lobes and parietal lobes via the
      cerebello-thalamo-cortical pathway. We propose that the effects of anodal
      stimulation of the cerebellar cortex upon cerebral cortical rhythms are mediated
      by this key-pathway. Additional studies using high-density EEG recordings and
      behavioral correlates are now required to confirm our findings, especially given
      the limited coverage of Epoc headset.

PMID- 28503137
TI  - Reward Network Immediate Early Gene Expression in Mood Disorders.
AB  - Over the past three decades, it has become clear that aberrant function of the
      network of interconnected brain regions responsible for reward processing and
      motivated behavior underlies a variety of mood disorders, including depression
      and anxiety. It is also clear that stress-induced changes in reward network
      activity underlying both normal and pathological behavior also cause changes in
      gene expression. Here, we attempt to define the reward circuitry and explore the
      known and potential contributions of activity-dependent changes in gene
      expression within this circuitry to stress-induced changes in behavior related to
      mood disorders, and contrast some of these effects with those induced by exposure
      to drugs of abuse. We focus on a series of immediate early genes regulated by
      stress within this circuitry and their connections, both well-explored and
      relatively novel, to circuit function and subsequent reward-related behaviors. We
      conclude that IEGs play a crucial role in stress-dependent remodeling of reward
      circuitry, and that they may serve as inroads to the molecular, cellular, and
      circuit-level mechanisms of mood disorder etiology and treatment.

PMID- 28503141
TI  - Addiction as an Attachment Disorder: White Matter Impairment Is Linked to
      Increased Negative Affective States in Poly-Drug Use.
AB  - Substance use disorders (SUD) have been shown to be linked to various neuronal
      and behavioral impairments. In this study, we investigate whether there is a
      connection between the integrity of white matter (WM) and attachment styles as
      well as different affective states including spirituality in a group of patients
      diagnosed for poly-drug use disorder (PUD) in comparison to non-clinical
      controls. A total sample of 59 right-handed men, comprising the groups of
      patients with PUD (n = 19), recreational drug-using individuals (RUC; n = 20) as
      well as non-drug using controls were recruited (NUC; n = 20). For the behavioral
      assessment, we applied the Adult Attachment-Scale, the Affective Neuroscience
      Personality-Scale (short version) and the Multidimensional Inventory for
      Religious/Spiritual Well-Being. Diffusion Tensor Imaging was used to investigate
      differences in WM neural connectivity. Analyses revealed decreased Fractional
      Anisotropy and decreased Mean Diffusivity in PUD patients as compared to RUC and
      NUC. No differences were found between RUC and NUC. Additional ROI analyses
      suggested that WM impairment in the superior longitudinal fasciculus (SLF) and
      the superior corona radiata (SCR) was linked to more insecure attachment as well
      as to more negative affectivity. No substantial correlation was observed with
      spirituality. These findings are mainly limited by the cross-sectional design of
      the study. However, our preliminary results support the idea of addiction as an
      attachment disorder, both at neuronal and behavioral levels. Further research
      might be focused on the changes of insecure attachment patterns in SUD treatment
      and their correlation with changes in the brain.

PMID- 28503138
TI  - Enhanced Feedback-Related Negativity in Alzheimer's Disease.
AB  - Alzheimer's disease (AD), the most common cause of dementia in the elderly,
      results in the impairment of executive function, including that of performance
      monitoring. Feedback-related negativity (FRN) is an electrophysiological measure
      reflecting the activity of this monitoring system via feedback signals, and is
      generated from the anterior cingulate cortex. However, there have been no reports
      on FRN in AD. Based on prior aging studies, we hypothesized that FRN would
      decrease in AD patients. To assess this, FRN was measured in healthy individuals
      and those with AD during a simple gambling task involving positive and negative
      feedback stimuli. Contrary to our hypothesis, FRN amplitude increased in AD
      patients, compared with the healthy elderly. We speculate that this may reflect
      the existence of a compensatory mechanism against the decline in executive
      function. Also, there was a significant association between FRN amplitude and
      depression scores in AD, and the FRN amplitude tended to increase insomuch as the
      Self-rating Depression Scale (SDS) was higher. This result suggests the existence
      of a negative bias in the affective state in AD. Thus, the impaired functioning
      monitoring system in AD is a more complex phenomenon than we thought.

PMID- 28503142
TI  - Brain Gray Matter Atrophy after Spinal Cord Injury: A Voxel-Based Morphometry
      Study.
AB  - The aim of this study was to explore possible changes in whole brain gray matter
      volume (GMV) after spinal cord injury (SCI) using voxel-based morphometry (VBM),
      and to study their associations with the injury duration, severity, and clinical
      variables. In total, 21 patients with SCI (10 with complete and 11 with
      incomplete SCI) and 21 age- and sex-matched healthy controls (HCs) were
      recruited. The 3D high-resolution T1-weighted structural images of all subjects
      were obtained using a 3.0 Tesla MRI system. Disease duration and American Spinal
      Injury Association (ASIA) Scale scores were also obtained from each patient.
      Voxel-based morphometry analysis was carried out to investigate the differences
      in GMV between patients with SCI and HCs, and between the SCI sub-groups.
      Associations between GMV and clinical variables were also analyzed. Compared with
      HCs, patients with SCI showed significant GMV decrease in the dorsal anterior
      cingulate cortex, bilateral anterior insular cortex, bilateral orbital frontal
      cortex (OFC), and right superior temporal gyrus. No significant difference in GMV
      in these areas was found either between the complete and incomplete SCI sub
      groups, or between the sub-acute (duration <1 year) and chronic (duration >1
      year) sub-groups. Finally, the GMV of the right OFC was correlated with the
      clinical motor scores of left extremities in not only all SCI patients, but
      especially the CSCI subgroup. In the sub-acute subgroup, we found a significant
      positive correlation between the dACC GMV and the total clinical motor scores,
      and a significant negative correlation between right OFC GMV and the injury
      duration. These findings indicate that SCI can cause remote atrophy of brain gray
      matter, especially in the salient network. In general, the duration and severity
      of SCI may be not associated with the degree of brain atrophy in total SCI
      patients, but there may be associations between them in subgroups.

PMID- 28503140
TI  - Gravity as a Strong Prior: Implications for Perception and Action.
AB  - In the future, humans are likely to be exposed to environments with altered
      gravity conditions, be it only visually (Virtual and Augmented Reality), or
      visually and bodily (space travel). As visually and bodily perceived gravity as
      well as an interiorized representation of earth gravity are involved in a series
      of tasks, such as catching, grasping, body orientation estimation and spatial
      inferences, humans will need to adapt to these new gravity conditions.
      Performance under earth gravity discrepant conditions has been shown to be
      relatively poor, and few studies conducted in gravity adaptation are rather
      discouraging. Especially in VR on earth, conflicts between bodily and visual
      gravity cues seem to make a full adaptation to visually perceived earth
      discrepant gravities nearly impossible, and even in space, when visual and bodily
      cues are congruent, adaptation is extremely slow. We invoke a Bayesian framework
      for gravity related perceptual processes, in which earth gravity holds the status
      of a so called "strong prior". As other strong priors, the gravity prior has
      developed through years and years of experience in an earth gravity environment.
      For this reason, the reliability of this representation is extremely high and
      overrules any sensory information to its contrary. While also other factors such
      as the multisensory nature of gravity perception need to be taken into account,
      we present the strong prior account as a unifying explanation for empirical
      results in gravity perception and adaptation to earth-discrepant gravities.

PMID- 28503143
TI  - Impairments of Motor Function While Multitasking in HIV.
AB  - Human immunodeficiency virus (HIV) became a treatable illness with the
      introduction of combination antiretroviral therapy (CART). As a result, patients
      with regular access to CART are expected to live decades with HIV. Long-term HIV
      infection presents unique challenges, including neurocognitive impairments
      defined by three major stages of HIV-associated neurocognitive disorders (HAND).
      The current investigation aimed to study cognitive and motor impairments in HIV
      using a novel multitasking paradigm. Unlike current standard measures of
      cognitive and motor performance in HIV, multitasking increases real-world
      validity by mimicking the dual motor and cognitive demands that are part of daily
      professional and personal settings (e.g., driving, typing and writing). Moreover,
      multitask assessments can unmask compensatory mechanisms, normally used under
      single task conditions, to maintain performance. This investigation revealed that
      HIV+ participants were impaired on the motor component of the multitask, while
      cognitive performance was spared. A patient-specific positive interaction between
      motor performance and working memory recall was driven by poor HIV+ multitaskers.
      Surprisingly, HAND stage did not correspond with multitask performance and a
      variety of commonly used assessments indicated normal motor function among HIV+
      participants with poor motor performance during the experimental task. These
      results support the use of multitasks to reveal otherwise hidden impairment in
      chronic HIV by expanding the sensitivity of clinical assessments used to
      determine HAND stage. Future studies should examine the capability of multitasks
      to predict performance in personal, professional and health-related behaviors and
      prognosis of patients living with chronic HIV.

PMID- 28503145
TI  - A Neural-Dynamic Architecture for Concurrent Estimation of Object Pose and
      Identity.
AB  - Handling objects or interacting with a human user about objects on a shared
      tabletop requires that objects be identified after learning from a small number
      of views and that object pose be estimated. We present a neurally inspired
      architecture that learns object instances by storing features extracted from a
      single view of each object. Input features are color and edge histograms from a
      localized area that is updated during processing. The system finds the best
      matching view for the object in a novel input image while concurrently estimating
      the object's pose, aligning the learned view with current input. The system is
      based on neural dynamics, computationally operating in real time, and can handle
      dynamic scenes directly off live video input. In a scenario with 30 everyday
      objects, the system achieves recognition rates of 87.2% from a single training
      view for each object, while also estimating pose quite precisely. We further
      demonstrate that the system can track moving objects, and that it can segment the
      visual array, selecting and recognizing one object while suppressing input from
      another known object in the immediate vicinity. Evaluation on the COIL-100
      dataset, in which objects are depicted from different viewing angles, revealed
      recognition rates of 91.1% on the first 30 objects, each learned from four
      training views.

PMID- 28503144
TI  - Rigid Ankle Foot Orthosis Deteriorates Mediolateral Balance Control and Vertical
      Braking during Gait Initiation.
AB  - Rigid ankle-foot orthoses (AFO) are commonly used for impeding foot drop during
      the swing phase of gait. They also reduce pain and improve gait kinematics in
      patients with weakness or loss of integrity of ankle-foot complex structures due
      to various pathological conditions. However, this comes at the price of
      constraining ankle joint mobility, which might affect propulsive force generation
      and balance control. The present study examined the effects of wearing an AFO on
      biomechanical variables and electromyographic activity of tibialis anterior (TA)
      and soleus muscles during gait initiation (GI). Nineteen healthy adults
      participated in the study. They initiated gait at a self-paced speed with no
      ankle constraint as well as wearing an AFO on the stance leg, or bilaterally.
      Constraining the stance leg ankle decreased TA activity ipsilaterally during the
      anticipatory postural adjustment (APA) of GI, and ipsilateral soleus activity
      during step execution. In the sagittal plane, the decrease in the stance leg TA
      activity reduced the backward displacement of the center of pressure (CoP)
      resulting in a reduction of the forward velocity of the center of mass (CoM)
      measured at foot contact (FC). In the frontal plane, wearing the AFO reduced the
      displacement of the CoP in the direction of the swing leg during the APA phase.
      The mediolateral velocity of the CoM increased during single-stance prompting a
      larger step width to recover balance. During step execution, the CoM vertical
      downward velocity is normally reduced in order to lessen the impact of the swing
      leg with the floor and facilitates the rise of the CoM that occurs during the
      subsequent double-support phase. The reduction in stance leg soleus activity
      caused by constraining the ankle weakened the vertical braking of the CoM during
      step execution. This caused the absolute instantaneous vertical velocity of the
      CoM at FC to be greater in the constrained conditions with respect to the control
      condition. From a rehabilitation perspective, passively- or actively-powered
      assistive AFOs could correct for the reduction in muscle activity and enhance
      balance control during GI of patients.

PMID- 28503146
TI  - Statin Therapy Is Associated with Reduced Risk of Peptic Ulcer Disease in the
      Taiwanese Population.
AB  - Although statin use may affect the severity of chronic gastritis and gastric
      cancer, no data exists about the relationship between statin therapy and risk of
      peptic ulcer disease (PUD) in patients. We investigated the effect of statin use
      and the incidence of PUD from the Taiwan National Health Insurance Research
      Database (NHIRD). A total of 35,194 patients records for medical claims were
      enrolled. We performed a population-based case-control analysis to compare the
      incidence of PUD in patients who were prescribed statins and that in patients who
      were not. In the univariate logistic analysis, we found that statin was not
      significant risk of PUD. However, a multivariate model indicates that satin use
      was significantly associated with a reduced risk of PUD (adjusted odds ratio
      [aOR] = 0.87, 95% CI = 0.82-0.93, P < 0.001). The cumulative defined daily dose
      (DDD) was analyzed. Patients who prescribed fluvastatin >=280 DDD, atorvastatin
      >=200 DDD, and pravastatin >=130 DDD dramatically decreased risk for PUD (aOR =
      0.58, 0.67, and 0.71; 95% CI = 0.46-0.74, 0.57-0.78, and 0.56-0.91,
      respectively). Our results showed that statin therapy reduced the risk of PUD and
      this was associated with the high cumulative DDD of prescribed statins. This
      study reveals that active use of statins to be associated with decreased risk for
      PUD.

PMID- 28503147
TI  - An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects
      and Potently Inhibits STAT3 Signaling In Vitro.
AB  - Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and
      mortality worldwide. Signal transducer and activator of transcription 3 (STAT3)
      signaling is constantly activated in CRC, and has been proposed as a pathogenic
      factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional
      Chinese medicinal herb, possesses low toxicity and has long been used clinically
      for the treatment of cancers including CRC. Some constituents of AR have been
      reported to exert anti-cancer properties by targeting STAT3. However, the anti
      CRC mode and mechanism of action of AR have not been fully elucidated. Here, we
      investigated the involvement of STAT3 signaling in the anti-CRC effects of AR.
      Results showed that AR reduced cell viability, induced cell apoptosis, and
      suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells.
      Mechanistic studies showed that AR potently suppressed STAT3 and Src
      phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells.
      AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP
      2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect
      of AR was diminished by overexpressing STAT3C, a persistent active variant of
      STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are
      at least in part attributed to the inhibition of STAT3 signaling. Our findings
      provide a molecular justification for the traditional use of AR in treating CRC,
      and a pharmacological basis for developing AR-derived modern anti-CRC agent(s).

PMID- 28503148
TI  - Management of Benign Prostatic Hyperplasia: Could Dietary Polyphenols Be an
      Alternative to Existing Therapies?
AB  - The incidence of benign prostatic hyperplasia (BPH) is gradually on the increase.
      While conventional drugs such as the alpha1-adrenergic receptor antagonists and
      5alpha-reductase inhibitors have been found to be useful in the treatment of BPH,
      the adverse side effects associated with their usage, have led to increased
      search for alternative means of managing this disease. Furthermore, although
      surgery has also been suggested to be a sure method, the cost and risks
      associated with it excludes it as a routine treatment. Dietary polyphenols have
      gained public interest in recent times due to their roles in the prevention of
      various diseases that implicate free radicals/reactive oxygen species. However,
      their roles in the management of BPH have not been explored. Hence, this review
      on their prospects in the management of BPH and their mechanisms of action.
      Literature search was carried out in several electronic data bases such as
      PubMed, Google Scholar, Medline, Agora, and Hinari from1970 to 2017 to identify
      the current status of knowledge on this concept. The findings from these data
      bases suggest that while dietary polyphenols may not replace the need for the
      existing therapies in the management of BPH, they hold promise in BPH management
      which could be explored by researchers working in this field.

PMID- 28503149
TI  - Vascular Kinin B1 and B2 Receptors Determine Endothelial Dysfunction through
      Neuronal Nitric Oxide Synthase.
AB  - B1- and B2-kinin receptors are G protein-coupled receptors that play an important
      role in the vascular function. Therefore, the present study was designed to
      evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced
      vascular relaxation, focusing on the protein-protein interaction involving kinin
      receptors with endothelial and neuronal nitric oxide synthases (eNOS and nNOS).
      Vascular reactivity, nitric oxide (NO.) and reactive oxygen species (ROS)
      generation, co-immunoprecipitation were assessed in thoracic aorta from male wild
      type (WT), B1- (B1R-/-), B2- (B2R-/-) knockout mice. Some vascular reactivity
      experiments were also performed in a double kinin receptors knockout mice (B1B2R
      /-). For pharmacological studies, selective B1- and B2-kinin receptors
      antagonists, NOS inhibitors and superoxide dismutase (SOD) mimetic were used.
      First, we show that B1- and B2-kinin receptors form heteromers with nNOS and eNOS
      in thoracic aorta. To investigate the functionality of these protein-protein
      interactions, we took advantage of pharmacological tools and knockout mice.
      Importantly, our results show that kinin receptors regulate ACh-induced
      relaxation via nNOS signaling in thoracic aorta with no changes in NO. donor
      induced relaxation. Interestingly, B1B2R-/- presented similar level of vascular
      dysfunction as found in B1R-/- or B2R-/- mice. In accordance, aortic rings from
      B1R-/- or B2R-/- mice exhibit decreased NO. bioavailability and increased
      superoxide generation compared to WT mice, suggesting the involvement of
      excessive ROS generation in the endothelial dysfunction of B1R-/- and B2R-/-
      mice. Alongside, we show that impaired endothelial vasorelaxation induced by ACh
      in B1R-/- or B2R-/- mice was rescued by the SOD mimetic compound. Taken together,
      our findings show that B1- and B2-kinin receptors regulate the endothelium
      dependent vasodilation of ACh through nNOS activity and indicate that molecular
      disturbance of short-range interaction between B1- and B2-kinin receptors with
      nNOS might be involved in the oxidative pathogenesis of endothelial dysfunction.

PMID- 28503150
TI  - Dental Pulp Cells Isolated from Teeth with Superficial Caries Retain an
      Inflammatory Phenotype and Display an Enhanced Matrix Mineralization Potential.
AB  - We have isolated dental pulp cells (DPCs) from three healthy (hDPCs) and three
      carious (cDPCs) donors and shown that compared to hDPCs cells isolated from
      superficial carious lesions show higher clonogenic potential; show an equivalent
      proportion of cells with putative stem cell surface markers; show enhanced matrix
      mineralization capability; have enhanced angiogenic marker expression and retain
      the inflammatory phenotype in vitro characteristic of superficial caries lesions
      in vivo. Our findings suggest that cDPCs may be used for further investigation of
      the cross talk between inflammatory, angiogenic and mineralization pathways in
      repair of carious pulp. In addition cells derived from carious pulps (almost
      always discarded) may have potential for future applications in mineralized
      tissue repair and regeneration.

PMID- 28503151
TI  - Identification of a Novel UT-B Urea Transporter in Human Urothelial Cancer.
AB  - The urea transporter UT-B is widely expressed and has been studied in
      erythrocyte, kidney, brain and intestines. Interestingly, UT-B gene has been
      found more abundant in bladder than any other tissue. Recently, gene analyses
      demonstrate that SLC14A1 (UT-B) gene mutations are associated with bladder
      cancer, suggesting that urea transporter UT-B may play an important role in
      bladder carcinogenesis. In this study, we examined UT-B expression in bladder
      cancer with human primary bladder cancer tissues and cancer derived cell lines.
      Human UT-B has two isoforms. We found that normal bladder expresses long form of
      UT-B2 but was lost in 8 of 24 (33%) or significantly downregulated in 16 of 24
      (67%) of primary bladder cancer patients. In contrast, the short form of UT-B1
      lacking exon 3 was detected in 20 bladder cancer samples. Surprisingly, a 24-nt
      in-frame deletion in exon 4 in UT-B1 (UT-B1Delta24) was identified in 11 of 20
      (55%) bladder tumors. This deletion caused a functional defect of UT-B1.
      Immunohistochemistry revealed that UT-B protein levels were significantly
      decreased in bladder cancers. Western blot analysis showed a weak UT-B band of 40
      kDa in some tumors, consistent with UT-B1 gene expression detected by RT-PCR.
      Interestingly, bladder cancer associate UT-B1Delta24 was barely sialylated,
      reflecting impaired glycosylation of UT-B1 in bladder tumors. In conclusion,
      SLC14A1 gene and UT-B protein expression are significantly changed in bladder
      cancers. The aberrant UT-B expression may promote bladder cancer development or
      facilitate carcinogenesis induced by other carcinogens.

PMID- 28503152
TI  - Identification, Classification, and Expression Analysis of GRAS Gene Family in
      Malus domestica.
AB  - GRAS genes encode plant-specific transcription factors that play important roles
      in plant growth and development. However, little is known about the GRAS gene
      family in apple. In this study, 127 GRAS genes were identified in the apple
      (Malus domestica Borkh.) genome and named MdGRAS1 to MdGRAS127 according to their
      chromosomal locations. The chemical characteristics, gene structures and
      evolutionary relationships of the MdGRAS genes were investigated. The 127 MdGRAS
      genes could be grouped into eight subfamilies based on their structural features
      and phylogenetic relationships. Further analysis of gene structures, segmental
      and tandem duplication, gene phylogeny and tissue-specific expression with
      ArrayExpress database indicated their diversification in quantity, structure and
      function. We further examined the expression pattern of MdGRAS genes during apple
      flower induction with transcriptome sequencing. Eight higher MdGRAS (MdGRAS6, 26,
      28, 44, 53, 64, 107, and 122) genes were surfaced. Further quantitative reverse
      transcription PCR indicated that the candidate eight genes showed distinct
      expression patterns among different tissues (leaves, stems, flowers, buds, and
      fruits). The transcription levels of eight genes were also investigated with
      various flowering related treatments (GA3, 6-BA, and sucrose) and different
      flowering varieties (Yanfu No. 6 and Nagafu No. 2). They all were affected by
      flowering-related circumstance and showed different expression level. Changes in
      response to these hormone or sugar related treatments indicated their potential
      involvement during apple flower induction. Taken together, our results provide
      rich resources for studying GRAS genes and their potential clues in genetic
      improvement of apple flowering, which enriches biological theories of GRAS genes
      in apple and their involvement in flower induction of fruit trees.

PMID- 28503153
TI  - Investigating Engineered Ribonucleoprotein Particles to Improve Oral RNAi
      Delivery in Crop Insect Pests.
AB  - Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being
      investigated largely as an RNA interference (RNAi)-based resistance strategy
      against crop insect pests. However, limitations of this strategy include the
      sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane
      penetration. Working with the insect pest cotton boll weevil (Anthonomus
      grandis), we showed that the chimeric protein PTD-DRBD (peptide transduction
      domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein
      particle (RNP) that improves the effectiveness of the RNAi mechanism in the
      insect. The RNP slows down nuclease activity, probably by masking the dsRNA.
      Furthermore, PTD-mediated internalization in insect gut cells is achieved within
      minutes after plasma membrane contact, limiting the exposure time of the RNPs to
      gut nucleases. Therefore, the RNP provides an approximately 2-fold increase in
      the efficiency of insect gene silencing upon oral delivery when compared to naked
      dsRNA. Taken together, these data demonstrate the role of engineered RNPs in
      improving dsRNA stability and cellular entry, representing a path toward the
      design of enhanced RNAi strategies in GM plants against crop insect pests.

PMID- 28503154
TI  - Sedentary Patterns, Physical Activity, and Cardiorespiratory Fitness in
      Association to Glycemic Control in Type 2 Diabetes Patients.
AB  - Background: Sedentary behavior has been considered an independent risk factor for
      type-2 diabetes (T2D), with a negative impact on several physiological outcomes,
      whereas breaks in sedentary time (BST) have been proposed as a viable solution to
      mitigate some of these effects. However, little is known about the independent
      associations of sedentary pursuits, physical activity, and cardiorespiratory
      fitness (CRF) variables with glycemic control. We investigated the independent
      associations of total sedentary time, BST, moderate-to-vigorous physical activity
      (MVPA), and CRF with glycemic outcomes in patients with T2D. Methods: Total
      sedentary time, BST, and MVPA were assessed in 66 participants (29 women) with
      T2D, using accelerometry. Glucose and insulin were measured during a mixed meal
      tolerance test, with the respective calculations of HOMA-IR and Matsuda index.
      Glycated hemoglobin (HbA1c) was also analyzed. CRF was measured in a maximal
      treadmill test with breath-by-breath gases analysis. Multiple regressions were
      used for data analysis. Results: Regardless of CRF, total sedentary time was
      positively associated with HbA1c (beta = 0.25, p = 0.044). Adjusting for MVPA,
      total sedentary time was related to fasting glucose (beta = 0.32, p = 0.037). No
      associations between total sedentary time and the remaining glycemic outcomes,
      after adjusting for MVPA. BST had favorable associations with HOMA-IR (beta = 
      0.28, p = 0.047) and fasting glucose (beta = -0.25, p = 0.046), when adjusted for
      MVPA, and with HOMA-IR (beta = -0.25, p = 0.036), Matsuda index (beta = 0.26, p =
      0.036), and fasting glucose (beta = -0.22, p = 0.038), following adjustment for
      CRF. When adjusting for total sedentary time, only CRF yielded favorable
      associations with HOMA-IR (beta = -0.29, p = 0.039), fasting glucose (beta = 
      0.32, p = 0.012), and glucose at 120-min (beta = -0.26, p = 0.035), and no
      associations were found for MVPA with none of the metabolic outcomes. Conclusion:
      The results from this study suggest that sedentary time and patterns are relevant
      for the glycemic control in patients with T2D. Still, MVPA and CRF counteracted
      most of the associations for total sedentary time but not for the BST. MVPA was
      not associated with metabolic outcomes, and CRF lost some of the associations
      with glycemic indicators when adjusted for total sedentary time. Future
      interventions aiming to control/improve T2D must consider reducing and breaking
      up sedentary time as a viable strategy to improve glycemic control.

PMID- 28503155
TI  - DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining
      Virtual Reality and Augmented Reality.
AB  - The present paper explores the benefits and the capabilities of various emerging
      state-of-the-art interactive 3D and Internet of Things technologies and
      investigates how these technologies can be exploited to develop a more effective
      technology supported exposure therapy solution for social anxiety disorder.
      "DJINNI" is a conceptual design of an in vivo augmented reality (AR) exposure
      therapy mobile support system that exploits several capturing technologies and
      integrates the patient's state and situation by vision-based, audio-based, and
      physiology-based analysis as well as by indoor/outdoor localization techniques.
      DJINNI also comprises an innovative virtual reality exposure therapy system that
      is adaptive and customizable to the demands of the in vivo experience and
      therapeutic progress. DJINNI follows a gamification approach where rewards and
      achievements are utilized to motivate the patient to progress in her/his
      treatment. The current paper reviews the state of the art of technologies needed
      for such a solution and recommends how these technologies could be integrated in
      the development of an individually tailored and yet feasible and effective
      AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI
      could be part of classical cognitive behavioral treatment and how to validate
      such a setup.

PMID- 28503157
TI  - A Review of Self-regulated Learning: Six Models and Four Directions for Research.
AB  - Self-regulated learning (SRL) includes the cognitive, metacognitive, behavioral,
      motivational, and emotional/affective aspects of learning. It is, therefore, an
      extraordinary umbrella under which a considerable number of variables that
      influence learning (e.g., self-efficacy, volition, cognitive strategies) are
      studied within a comprehensive and holistic approach. For that reason, SRL has
      become one of the most important areas of research within educational psychology.
      In this paper, six models of SRL are analyzed and compared; that is, Zimmerman;
      Boekaerts; Winne and Hadwin; Pintrich; Efklides; and Hadwin, Jarvela and Miller.
      First, each model is explored in detail in the following aspects: (a) history and
      development, (b) description of the model (including the model figures), (c)
      empirical support, and (d) instruments constructed based on the model. Then, the
      models are compared in a number of aspects: (a) citations, (b) phases and
      subprocesses, (c) how they conceptualize (meta)cognition, motivation and emotion,
      (d) top-down/bottom-up, (e) automaticity, and (f) context. In the discussion, the
      empirical evidence from the existing SRL meta-analyses is examined and
      implications for education are extracted. Further, four future lines of research
      are proposed. The review reaches two main conclusions. First, the SRL models form
      an integrative and coherent framework from which to conduct research and on which
      students can be taught to be more strategic and successful. Second, based on the
      available meta-analytic evidence, there are differential effects of SRL models in
      light of differences in students' developmental stages or educational levels.
      Thus, scholars and teachers need to start applying these differential effects of
      the SRL models and theories to enhance students' learning and SRL skills.

PMID- 28503158
TI  - Image Feature Types and Their Predictions of Aesthetic Preference and
      Naturalness.
AB  - Previous research has investigated ways to quantify visual information of a scene
      in terms of a visual processing hierarchy, i.e., making sense of visual
      environment by segmentation and integration of elementary sensory input. Guided
      by this research, studies have developed categories for low-level visual features
      (e.g., edges, colors), high-level visual features (scene-level entities that
      convey semantic information such as objects), and how models of those features
      predict aesthetic preference and naturalness. For example, in Kardan et al.
      (2015a), 52 participants provided aesthetic preference and naturalness ratings,
      which are used in the current study, for 307 images of mixed natural and urban
      content. Kardan et al. (2015a) then developed a model using low-level features to
      predict aesthetic preference and naturalness and could do so with high accuracy.
      What has yet to be explored is the ability of higher-level visual features (e.g.,
      horizon line position relative to viewer, geometry of building distribution
      relative to visual access) to predict aesthetic preference and naturalness of
      scenes, and whether higher-level features mediate some of the association between
      the low-level features and aesthetic preference or naturalness. In this study we
      investigated these relationships and found that low- and high- level features
      explain 68.4% of the variance in aesthetic preference ratings and 88.7% of the
      variance in naturalness ratings. Additionally, several high-level features
      mediated the relationship between the low-level visual features and aaesthetic
      preference. In a multiple mediation analysis, the high-level feature mediators
      accounted for over 50% of the variance in predicting aesthetic preference. These
      results show that high-level visual features play a prominent role predicting
      aesthetic preference, but do not completely eliminate the predictive power of the
      low-level visual features. These strong predictors provide powerful insights for
      future research relating to landscape and urban design with the aim of maximizing
      subjective well-being, which could lead to improved health outcomes on a larger
      scale.

PMID- 28503156
TI  - Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A
      Systematic Review of Longitudinal 1H-MRS Studies.
AB  - Schizophrenia is associated with brain glutamate dysfunction, but it is currently
      unclear whether antipsychotic administration can reduce the extent of
      glutamatergic abnormality. We conducted a systematic review of proton magnetic
      resonance spectroscopy (1H-MRS) studies examining the effects of antipsychotic
      treatment on brain glutamate levels in schizophrenia. The Medline database was
      searched to identify relevant articles published until December 2016. Inclusion
      required that studies examined longitudinal changes in brain glutamate
      metabolites in patients with schizophrenia before and after initiation of first
      antipsychotic treatment or a switch in antipsychotic treatment. The searches
      identified eight eligible articles, with baseline and follow-up measures in a
      total of 168 patients. The majority of articles reported a numerical reduction in
      brain glutamate metabolites with antipsychotic treatment, and the estimated
      overall mean reduction of 6.5% in Glx (the combined signal from glutamate and
      glutamine) across brain regions. Significant reductions in glutamate metabolites
      in at least one brain region were reported in four of the eight studies, and none
      of the studies reported a significant glutamatergic increase after antipsychotic
      administration. Relationships between the degree of change in glutamate and the
      degree of improvement in symptoms have been inconsistent but may provide limited
      evidence that antipsychotic response may be associated with lower glutamate
      levels before treatment and a greater extent of glutamatergic reduction during
      treatment. Further longitudinal, prospective studies of glutamate and
      antipsychotic response are required to confirm these findings.

PMID- 28503159
TI  - Quantifying the Degree of Movement Dissimilarity between Two Distinct Action
      Scenarios: An Exploratory Approach with Procrustes Analysis.
AB  - Game consoles allow subjects to perform movements which are visually similar to
      the movements performed in 'real' world scenarios. Beyond entertainment, virtual
      reality devices are being used in several domains: sports performance; motor
      rehabilitation; training of risk professions. This article presents the
      Procrustes method to measure the degree of dissimilarity between movements
      performed in 'real' and 'virtual' scenarios. For this purpose, the 501 darts game
      and a video darts game played on a console were used. The participants' arm
      throwing movements were video recorded and digitized. The matrices of x and y
      coordinates of the movements of the wrist, elbow, and shoulder in both
      performance scenarios were subjected to the Procrustes method. The wrist displays
      the most extreme dissimilarity values (higher than elbow and shoulder). Results
      also revealed smaller dissimilarity values for movements performed under the same
      conditions (e.g., real-real) and larger dissimilarity values between movements
      performed in different scenarios.

PMID- 28503160
TI  - Challenging Cognitive Control by Mirrored Stimuli in Working Memory Matching.
AB  - Cognitive conflict has often been investigated by placing automatic processing
      originating from learned associations in competition with instructed task
      demands. Here we explore whether mirror generalization as a congenital mechanism
      can be employed to create cognitive conflict. Past research suggests that the
      visual system automatically generates an invariant representation of visual
      objects and their mirrored counterparts (i.e., mirror generalization), and
      especially so for lateral reversals (e.g., a cup seen from the left side vs.
      right side). Prior work suggests that mirror generalization can be reduced or
      even overcome by learning (i.e., for those visual objects for which it is not
      appropriate, such as letters d and b). We, therefore, minimized prior practice on
      resolving conflicts involving mirror generalization by using kanji stimuli as non
      verbal and unfamiliar material. In a 1-back task, participants had to check a
      stream of kanji stimuli for identical repetitions and avoid miss-categorizing
      mirror reversed stimuli as exact repetitions. Consistent with previous work,
      lateral reversals led to profound slowing of reaction times and lower accuracy in
      Experiment 1. Yet, different from previous reports suggesting that lateral
      reversals lead to stronger conflict, similar slowing for vertical and horizontal
      mirror transformations was observed in Experiment 2. Taken together, the results
      suggest that transformations of visual stimuli can be employed to challenge
      cognitive control in the 1-back task.

PMID- 28503161
TI  - Exploring Task-Specific Independent Standing in 3- to 5-Month-Old Infants.
AB  - Perspectives on developmental milestones suggest that an infant's ability to
      stand without support occurs at the age of 9-16 months. The two exploratory tasks
      were part of a baby swimming routine, conducted over a period of 12 weeks (24
      sessions), and the aim was to examine whether young infants (mean age 97 days)
      improved their performance in standing as measured by prolonged time-to-stand.
      The data suggest that 3- to 5-month-old infants are capable of demonstrating
      signs of motor learning in task-specific standing. The results appear remarkable
      when compared to the expected age required for other forms of independent
      standing. The developmental process of independent standing is discussed in
      relation to the complex interaction between genetic and environmental factors.

PMID- 28503162
TI  - New Evaluation of the Electronically Activated Recorder (EAR): Obtrusiveness,
      Compliance, and Participant Self-selection Effects.
AB  - The Electronically Activated Recorder (EAR) is a method for collecting periodic
      brief audio snippets of participants' daily lives using a portable recording
      device. The EAR can potentially intrude into people's privacy, alter their
      natural behavior, and introduce self-selection biases greater than in other types
      of social science methods. Previous research (Mehl and Holleran, 2007, hereafter
      M&H) has shown that participant non-compliance with, and perceived obtrusiveness
      of, an EAR protocol are both low. However, these questions have not been
      addressed in jurisdictions that require the consent of all parties to recording
      conversations. This EAR study required participants to wear a button bearing a
      microphone icon and the words "This conversation may be recorded" to comply with
      California's all-party consent law. Results revealed self-reported obtrusiveness
      and non-compliance were actually lower in the present study than in the M&H
      study. Behaviorally assessed non-compliance did not differ between the two
      studies. Participants in the present study talked more about being in the study
      than participants in the M&H study, but such talk still comprised <2% of sampled
      conversations. Another potential problem with the EAR, participant self-selection
      bias, was addressed by comparing the EAR volunteers' HEXACO personality
      dimensions to a non-volunteer sample drawn from the same student population. EAR
      volunteers were significantly and moderately higher in Conscientiousness, and
      lower in Emotionality, than non-volunteers. In conclusion, the EAR method can be
      successfully implemented in at least one all-party consent state (California).
      Interested researchers are encouraged to review this procedure with their own
      legal counsel.

PMID- 28503163
TI  - Different Effects of Cold Stimulation on Reflex and Non-Reflex Components of
      Poststroke Spastic Hypertonia.
AB  - OBJECTIVE: To use an established biomechanical approach to quantify reflex and
      non-reflex responses from spastic-paretic elbow flexors in response to controlled
      cold and heat stimulation. METHODS: Thirteen spastic-hemiplegic stroke subjects
      were tested in the experiment. The spastic elbow joint was stretched into
      extension for 50 degrees  at two speeds (5 degrees /s and 100 degrees /s) in a
      customized apparatus. Thermal stimulation (HEAT at heat pain threshold, COLD at 0
      degrees C, or BASELINE at room temperature) was applied to the thenar eminence of
      the contralateral hand immediately prior to stretching for at least 30 s.
      RESULTS: Total torque was greater at 100 degrees /s than at 5 degrees /s. Total
      torque was significantly increased after COLD, but not HEAT as compared to
      BASELINE. When normalized to total torque at baseline, HEAT decreased total
      torque by 6.3%, while COLD increased total torque by 11.0%. There was no
      significant difference in the reflex torque among three thermal conditions.
      CONCLUSION: The findings demonstrate differentiated effects of cold stimulation
      on the total resistance from spastic muscles. They provide objective evidence for
      anecdotal clinical observations of increased muscle spasticity by cold exposure.

PMID- 28503164
TI  - Superior Canal Dehiscence Syndrome: Lessons from the First 20 Years.
AB  - Superior semicircular canal dehiscence syndrome was first reported by Lloyd Minor
      and colleagues in 1998. Patients with a dehiscence in the bone overlying the
      superior semicircular canal experience symptoms of pressure or sound-induced
      vertigo, bone conduction hyperacusis, and pulsatile tinnitus. The initial series
      of patients were diagnosed based on common symptoms, a physical examination
      finding of eye movements in the plane of the superior semicircular canal when ear
      canal pressure or loud tones were applied to the ear, and high-resolution
      computed tomography imaging demonstrating a dehiscence in the bone over the
      superior semicircular canal. Research productivity directed at understanding
      better methods for diagnosing and treating this condition has substantially
      increased over the last two decades. We now have a sound understanding of the
      pathophysiology of third mobile window syndromes, higher resolution imaging
      protocols, and several sensitive and specific diagnostic tests. Furthermore, we
      have a treatment (surgical occlusion of the superior semicircular canal) that has
      demonstrated efficacy. This review will highlight some of the fundamental
      insights gained in SCDS, propose diagnostic criteria, and discuss future research
      directions.

PMID- 28503166
TI  - Inhibition of Ectopic Arginine Vasopressin Production by Phenytoin in the Small
      Cell Lung Cancer Cell Line Lu-165.
AB  - Phenytoin, a voltage-gated sodium channel (NaV channel) antagonist, reportedly
      inhibits arginine vasopressin (AVP) release from an isolated rat neurohypophysis.
      So far, it is uncertain whether phenytoin has a direct action on ectopic AVP
      producing neuroendocrine tumors. We studied the effect of phenytoin on the
      release of copeptin, the C-terminal fragment of pro-AVP, and expression of AVP
      gene in the human small cell lung cancer cell line Lu-165. Cells were maintained
      in RPMI1640 medium with 10% fetal bovine serum and were used within the fifth
      passage. Copeptin was detected using a new sandwich immunoassay, and AVP mRNA
      levels were measured using real-time reverse transcription polymerase chain
      reaction. Treatment with phenytoin at a concentration of 25 ug/mL, but not at 5
      or 10 ug/mL, had an inhibitory effect on copeptin levels in the medium at 48 h.
      At the same concentration, AVP mRNA levels in Lu-165 cells also decreased.
      Although a sodium challenge with added sodium at 20 mEq/L increased copeptin
      levels in the medium, a sodium challenge with added sodium at 10 and 20 mEq/L had
      no effect on AVP mRNA levels. Phenytoin at a concentration of 25 ug/mL suppressed
      copeptin levels in the medium under the sodium challenge with added sodium at 10
      and 20 mEq/L. Phenytoin at a concentration of 25 ug/mL also decreased AVP mRNA
      levels in Lu-165 cells under the sodium challenge with added sodium at 10 mEq/L,
      but not at 20 mEq/L. Among five tested NaV channel subunits, NaV1.3 was highly
      expressed in Lu-165 cells. However, phenytoin significantly decreased NaV1.3 mRNA
      levels under the sodium challenge with added sodium at 10 and 20 mEq/L. These
      results suggest that Lu-165 cells are sensitive to phenytoin and sodium to
      control of AVP release and its gene expression. Phenytoin might have a direct
      action on ectopic AVP-producing tumors, suggesting the importance of NaV channels
      in AVP-producing neuroendocrine tumors.

PMID- 28503169
TI  - Cytotoxicity, Intestinal Transport, and Bioavailability of Dispersible Iron and
      Zinc Supplements.
AB  - Iron or zinc deficiency is one of the most important nutritional disorders which
      causes health problem. However, food fortification with minerals often induces
      unacceptable organoleptic changes during preparation process and storage, has low
      bioavailability and solubility, and is expensive. Nanotechnology surface
      modification to obtain novel characteristics can be a useful tool to overcome
      these problems. In this study, the efficacy and potential toxicity of dispersible
      Fe or Zn supplement coated in dextrin and glycerides (SunActive FeTM and
      SunActive ZnTM) were evaluated in terms of cytotoxicity, intestinal transport,
      and bioavailability, as compared with each counterpart without coating, ferric
      pyrophosphate (FePP) and zinc oxide (ZnO) nanoparticles (NPs), respectively. The
      results demonstrate that the cytotoxicity of FePP was not significantly affected
      by surface modification (SunActive FeTM), while SunActive ZnTM was more cytotoxic
      than ZnO-NPs. Cellular uptake and intestinal transport efficiency of SunActive
      FeTM were significantly higher than those of its counterpart material, which was
      in good agreement with enhanced oral absorption efficacy after a single-dose oral
      administration to rats. These results seem to be related to dissolution, particle
      dispersibility, and coating stability of materials depending on suspending media.
      Both SunActiveTM products and their counterpart materials were determined to be
      primarily transported by microfold (M) cells through the intestinal epithelium.
      It was, therefore, concluded that surface modification of food fortification will
      be a useful strategy to enhance oral absorption efficiency at safe levels.

PMID- 28503167
TI  - The Impact of Space Flight on Survival and Interaction of Cupriavidus
      metallidurans CH34 with Basalt, a Volcanic Moon Analog Rock.
AB  - Microbe-mineral interactions have become of interest for space exploration as
      microorganisms could be used to biomine from extra-terrestrial material and
      extract elements useful as micronutrients in life support systems. This research
      aimed to identify the impact of space flight on the long-term survival of
      Cupriavidus metallidurans CH34 in mineral water and the interaction with basalt,
      a lunar-type rock in preparation for the ESA spaceflight experiment, BIOROCK.
      Therefore, C. metallidurans CH34 cells were suspended in mineral water
      supplemented with or without crushed basalt and send for 3 months on board the
      Russian FOTON-M4 capsule. Long-term storage had a significant impact on cell
      physiology and energy status (by flow cytometry analysis, plate count and
      intracellular ATP measurements) as 60% of cells stored on ground lost their cell
      membrane potential, only 17% were still active, average ATP levels per cell were
      significantly lower and cultivability dropped to 1%. The cells stored in the
      presence of basalt and exposed to space flight conditions during storage however
      showed less dramatic changes in physiology, with only 16% of the cells lost their
      cell membrane potential and 24% were still active, leading to a higher
      cultivability (50%) and indicating a general positive effect of basalt and space
      flight on survival. Microbe-mineral interactions and biofilm formation was
      altered by spaceflight as less biofilm was formed on the basalt during flight
      conditions. Leaching from basalt also changed (measured with ICP-OES), showing
      that cells release more copper from basalt and the presence of cells also
      impacted iron and magnesium concentration irrespective of the presence of basalt.
      The flight conditions thus could counteract some of the detrimental effects
      observed after the 3 month storage conditions.

PMID- 28503165
TI  - Stress-Related and Circadian Secretion and Target Tissue Actions of
      Glucocorticoids: Impact on Health.
AB  - Living organisms are highly complex systems that must maintain a dynamic
      equilibrium or homeostasis that requires energy to be sustained. Stress is a
      state in which several extrinsic or intrinsic disturbing stimuli, the stressors,
      threaten, or are perceived as threatening, homeostasis. To achieve homeostasis
      against the stressors, organisms have developed a highly sophisticated system,
      the stress system, which provides neuroendocrine adaptive responses, to restore
      homeostasis. These responses must be appropriate in terms of size and/or
      duration; otherwise, they may sustain life but be associated with detrimental
      effects on numerous physiologic functions of the organism, leading to a state of
      disease-causing disturbed homeostasis or cacostasis. In addition to facing a
      broad spectrum of external and/or internal stressors, organisms are subject to
      recurring environmental changes associated with the rotation of the planet around
      itself and its revolution around the sun. To adjust their homeostasis and to
      synchronize their activities to day/night cycles, organisms have developed an
      evolutionarily conserved biologic system, the "clock" system, which influences
      several physiologic functions in a circadian fashion. Accumulating evidence
      suggests that the stress system is intimately related to the circadian clock
      system, with dysfunction of the former resulting in dysregulation of the latter
      and vice versa. In this review, we describe the functional components of the two
      systems, we discuss their multilevel interactions, and we present how excessive
      or prolonged activity of the stress system affects the circadian rhythm of
      glucocorticoid secretion and target tissue effects.

PMID- 28503168
TI  - Generation and Comprehensive Analysis of Host Cell Interactome of the PA Protein
      of the Highly Pathogenic H5N1 Avian Influenza Virus in Mammalian Cells.
AB  - Accumulating data have identified the important roles of PA protein in
      replication and pathogenicity of influenza A virus (IAV). Identification of host
      factors that interact with the PA protein may accelerate our understanding of IAV
      pathogenesis. In this study, using immunoprecipitation assay combined with liquid
      chromatography-tandem mass spectrometry, we identified 278 human cellular
      proteins that might interact with PA of H5N1 IAV. Gene Ontology annotation
      revealed that the identified proteins are highly associated with viral
      translation and replication. Further KEGG pathway analysis of the interactome
      profile highlighted cellular pathways associated with translation, infectious
      disease, and signal transduction. In addition, Diseases and Functions analysis
      suggested that these cellular proteins are highly related with Organismal Injury
      and Abnormalities and Cell Death and Survival. Moreover, two cellular proteins
      (nucleolin and eukaryotic translation elongation factor 1-alpha 1) identified
      both in this study and others were further validated to interact with PA using co
      immunoprecipitation and co-localization assays. Therefore, this study presented
      the interactome data of H5N1 IAV PA protein in human cells which may provide
      novel cellular target proteins for elucidating the potential molecular functions
      of PA in regulating the lifecycle of IAV in human cells.

PMID- 28503170
TI  - Drosophila melanogaster as a High-Throughput Model for Host-Microbiota
      Interactions.
AB  - Microbiota research often assumes that differences in abundance and identity of
      microorganisms have unique influences on host physiology. To test this concept
      mechanistically, germ-free mice are colonized with microbial communities to
      assess causation. Due to the cost, infrastructure challenges, and time-consuming
      nature of germ-free mouse models, an alternative approach is needed to
      investigate host-microbial interactions. Drosophila melanogaster (fruit flies)
      can be used as a high throughput in vivo screening model of host-microbiome
      interactions as they are affordable, convenient, and replicable. D. melanogaster
      were essential in discovering components of the innate immune response to
      pathogens. However, axenic D. melanogaster can easily be generated for microbiome
      studies without the need for ethical considerations. The simplified microbiota
      structure enables researchers to evaluate permutations of how each microbial
      species within the microbiota contribute to host phenotypes of interest. This
      enables the possibility of thorough strain-level analysis of host and microbial
      properties relevant to physiological outcomes. Moreover, a wide range of mutant
      D. melanogaster strains can be affordably obtained from public stock centers.
      Given this, D. melanogaster can be used to identify candidate mechanisms of host
      microbe symbioses relevant to pathogen exclusion, innate immunity modulation,
      diet, xenobiotics, and probiotic/prebiotic properties in a high throughput
      manner. This perspective comments on the most promising areas of microbiota
      research that could immediately benefit from using the D. melanogaster model.

PMID- 28503172
TI  - Hydrocarbon Degradation in Caspian Sea Sediment Cores Subjected to Simulated
      Petroleum Seepage in a Newly Designed Sediment-Oil-Flow-Through System.
AB  - The microbial community response to petroleum seepage was investigated in a whole
      round sediment core (16 cm length) collected nearby natural hydrocarbon seepage
      structures in the Caspian Sea, using a newly developed Sediment-Oil-Flow-Through
      (SOFT) system. Distinct redox zones established and migrated vertically in the
      core during the 190 days-long simulated petroleum seepage. Methanogenic petroleum
      degradation was indicated by an increase in methane concentration from 8 MUM in
      an untreated core compared to 2300 MUM in the lower sulfate-free zone of the SOFT
      core at the end of the experiment, accompanied by a respective decrease in the
      delta13C signal of methane from -33.7 to -49.50/00. The involvement of
      methanogens in petroleum degradation was further confirmed by methane production
      in enrichment cultures from SOFT sediment after the addition of hexadecane,
      methylnapthalene, toluene, and ethylbenzene. Petroleum degradation coupled to
      sulfate reduction was indicated by the increase of integrated sulfate reduction
      rates from 2.8 SO42-m-2 day-1 in untreated cores to 5.7 mmol SO42-m-2 day-1 in
      the SOFT core at the end of the experiment, accompanied by a respective
      accumulation of sulfide from 30 to 447 MUM. Volatile hydrocarbons (C2-C6 n
      alkanes) passed through the methanogenic zone mostly unchanged and were depleted
      within the sulfate-reducing zone. The amount of heavier n-alkanes (C10-C38)
      decreased step-wise toward the top of the sediment core and a preferential
      degradation of shorter (<C14) and longer chain n-alkanes (>C30) was seen during
      the seepage. This study illustrates, to the best of our knowledge, for the first
      time the development of methanogenic petroleum degradation and the succession of
      benthic microbial processes during petroleum passage in a whole round sediment
      core.

PMID- 28503171
TI  - Persistence of Salmonella Typhimurium LT2 in Soil Enhanced after Growth in
      Lettuce Medium.
AB  - The persistence of Salmonella in the environment is influenced by a multitude of
      biotic and abiotic factors. In addition, its persistence can be influenced by
      preadaptation before the introduction into the environment. In order to study how
      preadaptation changes the survival of Salmonella in soil and therefore its
      potential to colonize the phytosphere, we developed a new medium based on lettuce
      material [lettuce medium (LM)]. Salmonella enterica serovar Typhimurium strain
      LT2 was used as a model for Salmonella in this study. LT2 was inoculated into
      soil microcosms after pregrowth in Luria Bertani (LB) broth or in LM. Survival of
      LT2 in soil was monitored over 56 days by plate counts and quantification of the
      Typhimurium-specific gene STM4497 using qPCR in total community DNA for which
      primers and TaqMan probe were designed in this study. Significantly enhanced
      persistence was observed for LT2 pregrown in LM compared to LT2 pregrown in LB,
      indicating a preadaptation effect. Surprisingly, no improved survival could be
      observed for S. Typhimurium strain 14028s and S. enterica serovar Senftenberg
      after pregrowth on LM. This indicates a high strain specificity of preadaptation.
      Results from previous studies suggested that biofilm formation could enhance the
      survival of human pathogens in various environments and might contribute to
      enhanced survival on plants. In vitro biofilm assays with several Salmonella
      strains revealed a strain-specific effect of LM on the biofilm formation. While
      LM significantly improved the biofilm formation of S. Senftenberg, the biofilm
      formation of LT2 was better in LB. This indicates that the better survival of LM
      pregrown LT2 in soil was not linked to an improved ability to form biofilms but
      was likely due to other factors. Most importantly, this study showed that the
      medium used to pregrow Salmonella can influence its survival in soil and its
      biofilm formation which might influence the fate of Salmonella in soil.

PMID- 28503173
TI  - Microbial Community Response to Simulated Petroleum Seepage in Caspian Sea
      Sediments.
AB  - Anaerobic microbial hydrocarbon degradation is a major biogeochemical process at
      marine seeps. Here we studied the response of the microbial community to
      petroleum seepage simulated for 190 days in a sediment core from the Caspian Sea
      using a sediment-oil-flow-through (SOFT) system. Untreated (without simulated
      petroleum seepage) and SOFT sediment microbial communities shared 43% bacterial
      genus-level 16S rRNA-based operational taxonomic units (OTU0.945) but shared only
      23% archaeal OTU0.945. The community differed significantly between sediment
      layers. The detection of fourfold higher deltaproteobacterial cell numbers in
      SOFT than in untreated sediment at depths characterized by highest sulfate
      reduction rates and strongest decrease of gaseous and mid-chain alkane
      concentrations indicated a specific response of hydrocarbon-degrading
      Deltaproteobacteria. Based on an increase in specific CARD-FISH cell numbers, we
      suggest the following groups of sulfate-reducing bacteria to be likely
      responsible for the observed decrease in aliphatic and aromatic hydrocarbon
      concentration in SOFT sediments: clade SCA1 for propane and butane degradation,
      clade LCA2 for mid- to long-chain alkane degradation, clade Cyhx for
      cycloalkanes, pentane and hexane degradation, and relatives of Desulfobacula for
      toluene degradation. Highest numbers of archaea of the genus Methanosarcina were
      found in the methanogenic zone of the SOFT core where we detected preferential
      degradation of long-chain hydrocarbons. Sequencing of masD, a marker gene for
      alkane degradation encoding (1-methylalkyl)succinate synthase, revealed a low
      diversity in SOFT sediment with two abundant species-level MasD OTU0.96.

PMID- 28503174
TI  - Commentary: Modification of Host Responses by Mycobacteria.

PMID- 28503175
TI  - Heterogeneity of Phenotype and Function Reflects the Multistage Development of T
      Follicular Helper Cells.
AB  - T follicular helper cells (Tfh) provide crucial signals for germinal center (GC)
      formation, but Tfh populations are heterogeneous. While PD1hi Tfh are important
      in the GC response, the function of the PD1lo Tfh-like subset is unknown. We show
      that these cells, like the PD1hi GC-Tfh, depend upon B cells; however, their
      entry to follicles is independent of CXCR5 or cognate interactions with B cells.
      The differentiation into PD1hi Tfh is dependent on MHC class II interactions with
      B cells and requires CXCR5. Our data suggest a Tfh differentiation pathway that
      is initially B cell-independent, then dependent on non-cognate B cell
      interactions, and finally following cognate interaction with B cells and CXCR5
      ligands allows the formation of GC-Tfh. The PD1lo Tfh-like cells make early
      cytokine responses and may represent precursors of CD4 memory cells.

PMID- 28503176
TI  - Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of
      Autoimmune Retinopathy and Other Autoimmune Disorders.
AB  - Autoantibodies (AAbs) against glycolytic enzymes: aldolase, alpha-enolase,
      glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in
      sera of patients with blinding retinal diseases, such as paraneoplastic [cancer
      associated retinopathy (CAR)] and non-paraneoplastic autoimmune retinopathies, as
      well as in many other autoimmune diseases. CAR is a degenerative disease of the
      retina characterized by sudden vision loss in patients with cancer and serum anti
      retinal AAbs. In this review, we discuss the widespread serum presence of anti
      glycolytic enzyme AAbs and their significance in autoimmune diseases. There are
      multiple mechanisms responsible for antibody generation, including the innate
      anti-microbial response, anti-tumor response, or autoimmune response against
      released self-antigens from damaged, inflamed tissue. AAbs against enolase,
      GADPH, and aldolase exist in a single patient in elevated titers, suggesting
      their participation in pathogenicity. The lack of restriction of AAbs to one
      disease may be related to an increased expression of glycolytic enzymes in
      various metabolically active tissues that triggers an autoimmune response and
      generation of AAbs with the same specificity in several chronic and autoimmune
      conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been
      previously dismissed, but the retina may be without pathological consequence
      until a failure of the blood-retinal barrier function, which would then allow
      pathogenic AAbs access to their retinal targets, ultimately leading to damaging
      effects.

PMID- 28503177
TI  - The Innate Immune Cross Talk between NK Cells and Eosinophils Is Regulated by the
      Interaction of Natural Cytotoxicity Receptors with Eosinophil Surface Ligands.
AB  - Previous studies suggested that the cross talk between NK cells and other cell
      types is crucial for the regulation of both innate and adaptive immune responses.
      In the present study, we analyzed the phenotypic and functional outcome of the
      interaction between resting or cytokine-activated NK cells and eosinophils
      derived from non-atopic donors. Our results provide the first evidence that a
      natural cytotoxicity receptor (NCR)/NCR ligand-dependent cross talk between NK
      cells and eosinophils may be important to upregulate the activation state and the
      effector function of cytokine-primed NK cells. This interaction also promotes the
      NK-mediated editing process of dendritic cells that influence the process of Th1
      polarization. In turn, this cross talk also resulted in eosinophil activation and
      acquisition of the characteristic features of antigen-presenting cells. At higher
      NK/eosinophil ratios, cytokine-primed NK cells were found to kill eosinophils via
      NKp46 and NKp30, thus suggesting a potential immunoregulatory role for NK cells
      in dampening inflammatory responses involving eosinophils.

PMID- 28503178
TI  - Transcriptomic Response of Chinese Yew (Taxus chinensis) to Cold Stress.
AB  - Taxus chinensis is a rare and endangered shrub, highly sensitive to temperature
      changes and widely known for its potential in cancer treatment. How gene
      expression of T. chinensis responds to low temperature is still unknown. To
      investigate cold response of the genus Taxus, we obtained the transcriptome
      profiles of T. chinensis grown under normal and low temperature (cold stress, 0
      degrees C) conditions using Illumina Miseq sequencing. A transcriptome including
      83,963 transcripts and 62,654 genes were assembled from 4.16 Gb of reads data.
      Comparative transcriptomic analysis identified 2,025 differently expressed (DE)
      isoforms at p < 0.05, of which 1,437 were up-regulated by cold stress and 588
      were down-regulated. Annotation of DE isoforms indicated that transcription
      factors (TFs) in the MAPK signaling pathway and TF families of NAC, WRKY, bZIP,
      MYB, and ERF were transcriptionally activated. This might have been caused by the
      accumulation of secondary messengers, such as reactive oxygen species (ROS) and
      Ca2+. While accumulation of ROS will have caused damages to cells, our results
      indicated that to adapt to low temperatures T. chinensis employed a series of
      mechanisms to minimize these damages. The mechanisms included: (i) cold-enhanced
      expression of ROS deoxidant systems, such as peroxidase and phospholipid
      hydroperoxide glutathione peroxidase, to remove ROS. This was further confirmed
      by analyses showing increased activity of POD, SOD, and CAT under cold stress.
      (ii) Activation of starch and sucrose metabolism, thiamine metabolism, and purine
      metabolism by cold-stress to produce metabolites which either protect cell
      organelles or lower the ROS content in cells. These processes are regulated by
      ROS signaling, as the "feedback" toward ROS accumulation.

PMID- 28503179
TI  - Molecular and Evolutionary Mechanisms of Cuticular Wax for Plant Drought
      Tolerance.
AB  - Cuticular wax, the first protective layer of above ground tissues of many plant
      species, is a key evolutionary innovation in plants. Cuticular wax safeguards the
      evolution from certain green algae to flowering plants and the diversification of
      plant taxa during the eras of dry and adverse terrestrial living conditions and
      global climate changes. Cuticular wax plays significant roles in plant abiotic
      and biotic stress tolerance and has been implicated in defense mechanisms against
      excessive ultraviolet radiation, high temperature, bacterial and fungal
      pathogens, insects, high salinity, and low temperature. Drought, a major type of
      abiotic stress, poses huge threats to global food security and health of
      terrestrial ecosystem by limiting plant growth and crop productivity. The
      composition, biochemistry, structure, biosynthesis, and transport of plant
      cuticular wax have been reviewed extensively. However, the molecular and
      evolutionary mechanisms of cuticular wax in plants in response to drought stress
      are still lacking. In this review, we focus on potential mechanisms, from
      evolutionary, molecular, and physiological aspects, that control cuticular wax
      and its roles in plant drought tolerance. We also raise key research questions
      and propose important directions to be resolved in the future, leading to
      potential applications of cuticular wax for water use efficiency in agricultural
      and environmental sustainability.

PMID- 28503181
TI  - Development of a Critical Nitrogen Dilution Curve of Double Cropping Rice in
      South China.
AB  - The concept of critical nitrogen (Nc) concentration can be implemented to
      diagnose in-season plant nitrogen (N) status for optimizing N fertilizer
      management. The Nc dilution curves have been established for rice (Oryza sativa
      L.) grown in different climatic regions, yet no attempt has been made to develop
      the Nc dilution curve for double cropping rice regions. This study was undertaken
      to develop the Nc dilution curves for double cropping rice in south China for
      assessment of in-season N status and to establish the relationships N nutrition
      index (NNI) and relative yield (RY) for in-season prediction of rice grain yield.
      Three different N application rate field experiments using six Indica rice
      varieties, including two early rice hybrids and four late rice hybrids were
      carried out in east China. The Nc dilution curves based on whole plant N
      concentration were determined and described as, Nc = 3.37 W-0.44 for early rice
      and Nc = 3.69 W-0.34 for late rice. The constant N concentration at early growth
      stage was 3.31 and 3.15% DM for early and late rice, respectively. Late rice
      showed a higher capacity of N accumulation and a lower rate of N decline per unit
      shoot biomass as compared to early rice. The curves for present study were
      different from the existing reference curves for Indica and Japonica rice grown
      in different rice growing regions. Integrated N nutrition index (NNIint) based on
      Nc was used to estimate RY at different growth periods using linear regression
      functions. The results showed that the critical curves and relationship between
      NNIint and RY could be used as a reliable indicator of N status diagnosis, grain
      yield prediction as well as to provide technical support in N management for
      double cropping rice in south China.

PMID- 28503180
TI  - Transcriptomic Comparison Reveals Candidate Genes for Triterpenoid Biosynthesis
      in Two Closely Related Ilex Species.
AB  - Native to Southern China, Ilex pubescens and Ilex asprella are frequently used in
      traditional Chinese medicine. Both of them produce a large variety of ursane-type
      triterpenoid saponins, which have been demonstrated to have different
      pharmacological effects. However, little is known about their biosynthesis. In
      this study, transcriptomic analysis of I. pubescens and comparison with its
      closely related specie I. asprella were carried out to identify potential genes
      involved in triterpenoid saponin biosynthesis. Through RNA sequencing (RNA-seq)
      and de novo transcriptome assembly of I. pubescens, a total of 68,688 UniGene
      clusters are obtained, of which 32,184 (46.86%) are successfully annotated by
      comparison with the sequences in major public databases (NCBI, Swiss-Prot, and
      KEGG). It includes 128 UniGenes related to triterpenoid backbone biosynthesis, 11
      OSCs (oxidosqualene cyclases), 233 CYPs (cytochrome P450), and 269 UGTs (UDP
      glycosyltransferases). By homology-based blast and phylogenetic analysis with
      well-characterized genes involved in triterpenoid saponin biosynthesis, 5 OSCs,
      14 CYPs, and 1 UGT are further proposed as the most promising candidate genes.
      Transcriptomic comparison between two Ilex species using blastp and OrthoMCL
      method reveals high sequence similarity. All OSCs and UGTs as well as most CYPs
      are classified as orthologous genes, while only 5 CYPs in I. pubescens and 3 CYPs
      in I. asprella are species-specific. One of OSC candidates, named as IpAS1, was
      successfully cloned and expressed in Saccharomyces cerevisiae INVSc1. Analysis of
      the yeast extract by gas chromatography (GC) and gas chromatography-mass
      spectrometry (GC-MS) shows IpAS1 is a mixed amyrin synthase, producing alpha
      amyrin and beta-amyrin at ratio of 5:1, which is similar to its ortholog IaAS1
      from I. asprella. This study is the first exploration to profile the
      transcriptome of I. pubescens, the generated data and gene models will facilitate
      further molecular studies on the physiology and metabolism in this plant. By
      comparative transcriptomic analysis, a series of candidate genes involved in the
      biosynthetic pathway of triterpenoid saponins are identified, providing new
      insight into their biosynthesis at transcriptome level.

PMID- 28503182
TI  - Genome-Wide SNP Markers Based on SLAF-Seq Uncover Breeding Traces in Rapeseed
      (Brassica napus L.).
AB  - Single Nucleotide Polymorphisms (SNPs) are the most abundant and richest form of
      genomic polymorphism, and hence make highly favorable markers for genetic map
      construction and genome-wide association studies. In this study, a total of 300
      rapeseed accessions (278 representative of Chinese germplasm, plus 22 outgroup
      accessions of different origins and ecotypes) were collected and sequenced using
      Specific-Locus Amplified Fragment Sequencing (SLAF-seq) technology, obtaining
      660.25M reads with an average sequencing depth of 6.27 * and a mean Q30 of
      85.96%. Based on the 238,711 polymorphic SLAF tags a total of 1,197,282 SNPs were
      discovered, and a subset of 201,817 SNPs with minor allele frequency >0.05 and
      integrity >0.8 were selected. Of these, 30,877 were designated SNP "hotspots,"
      and 41 SNP-rich genomic regions could be delineated, with 100 genes associated
      with plant resistance, vernalization response, and signal transduction detected
      in these regions. Subsequent analysis of genetic diversity, linkage
      disequilibrium (LD), and population structure in the 300 accessions was carried
      out based on the 201,817 SNPs. Nine subpopulations were observed based on the
      population structure analysis. Hierarchical clustering and principal component
      analysis divided the 300 varieties roughly in accordance with their ecotype
      origins. However, spring-type varieties were intermingled with semi-winter type
      varieties, indicating frequent hybridization between spring and semi-winter
      ecotypes in China. In addition, LD decay across the whole genome averaged 299 kb
      when r2 = 0.1, but the LD decay in the A genome (43 kb) was much shorter than in
      the C genome (1,455 kb), supporting the targeted introgression of the A genome
      from progenitor species B. rapa into Chinese rapeseed. This study also lays the
      foundation for genetic analysis of important agronomic traits using this rapeseed
      population.

PMID- 28503185
TI  - Phosphate Uptake from Phytate Due to Hyphae-Mediated Phytase Activity by
      Arbuscular Mycorrhizal Maize.
AB  - Phytate is the most abundant form of soil organic phosphorus (P). Increased P
      nutrition of arbuscular mycorrhizal plants derived from phytate has been
      repeatedly reported. Earlier studies assessed acid phosphatase rather than
      phytase as an indication of mycorrhizal fungi-mediated phytate use. We
      investigated the effect of mycorrhizal hyphae-mediated phytase activity on P
      uptake by maize. Two maize (Zea mays L.) cultivars, non-inoculated or inoculated
      with the arbuscular mycorrhizal fungi Funneliformis mosseae or Claroideoglomus
      etunicatum, were grown for 45 days in two-compartment rhizoboxes, containing a
      root compartment and a hyphal compartment. The soil in the hyphal compartment was
      supplemented with 20, 100, and 200 mg P kg-1 soil as calcium phytate. We measured
      activity of phytase and acid phosphatase in the hyphal compartment, hyphal length
      density, P uptake, and plant biomass. Our results showed: (1) phytate addition
      increased phytase and acid phosphatase activity, and resulted in larger P uptake
      and plant biomass; (2) increases in P uptake and biomass were correlated with
      phytase activity but not with acid phosphatase activity; (3) lower phytate
      addition rate increased, but higher addition rate decreased hyphal length
      density. We conclude that P from phytate can be taken up by arbuscular
      mycorrhizal plants and that phytase plays a more important role in mineralizing
      phytate than acid phosphatase.

PMID- 28503183
TI  - Embolized Stems Recover Overnight in Zea mays: The Role of Soil Water, Root
      Pressure, and Nighttime Transpiration.
AB  - It is not currently well-understood how much xylem conductance is lost in maize
      plants during the day, if conductance is recovered during the night, or what soil
      water conditions are required for recovery to take place. To answer these
      questions we designed a greenhouse experiment whereby two genetically dissimilar
      maize genotypes were subjected to a level of water stress commonly experienced in
      the field (Psixylem ~-2 MPa). We then measured the loss of stem-specific
      conductivity associated with this level of stress, as well as the overnight
      recovery following three re-watering treatments: Psisoil ~ 0 MPa, Psisoil ~-0.40
      MPa, and Psisoil ~-1.70 MPa. Mid-day leaf water potentials of -1.98 MPa resulted
      in stem-specific conductivity (KS) values that were 31.5% of maximal (i.e., 68%
      loss). Returning soils to field capacity (Psisoil ~ 0 MPa) overnight allowed for
      the significant recovery of KS (76% of maximal), whereas partial watering
      (Psisoil ~-0.40 MPa) resulted KS values that were 51.7% of maximal values,
      whereas not watering resulted in no recovery (35.4% of maximal; Psisoil ~-1.7
      MPa). Recovery of KS was facilitated by the generation of root pressure and low
      rates of nighttime transpiration.

PMID- 28503184
TI  - An ABC Transporter Is Involved in the Silicon-Induced Formation of Casparian
      Bands in the Exodermis of Rice.
AB  - Silicon (Si) promotes the formation of Casparian bands (CB) in rice and reduces
      radial oxygen loss (ROL). Further transcriptomic approaches revealed several
      candidate genes involved in the Si-induced formation of CB such as ATP binding
      cassette (ABC) transporter, Class III peroxidases, ligases and transferases.
      Investigation of these genes by means of overexpression (OE) and knockout (KO)
      mutants revealed the contribution of the ABC transporter (OsABCG25) to CB
      formation in the exodermis, which was also reflected in the expression of other
      OsABCG25 in the Si-promoted formation of CB genes related to the phenylpropanoid
      pathway, such as phenylalanine-ammonia-lyase, diacylglycerol O-acyltransferase
      and 4-coumarate-CoA ligase. Differential CB development in mutants and Si supply
      also affected the barrier function of the exodermis. OE of the ABC transporter
      and Si supply reduced the ROL from roots and Fe uptake. No effect on ROL and Fe
      uptake could be observed for the KO mutant. The presented research confirms the
      impact of the OsABCG25 in the Si-promoted formation of CB and its barrier
      functions.

PMID- 28503186
TI  - The Pepper RING Finger E3 Ligase, CaDIR1, Regulates the Drought Stress Response
      via ABA-Mediated Signaling.
AB  - Drought stress from soil or air limits plant growth and development, leading to a
      reduction in crop productivity. Several E3 ligases positively or negatively
      regulate the drought stress response. In the present study, we show that the
      pepper (Capsicum annuum) Drought Induced RING type E3 ligase 1, CaDIR1, regulates
      the drought stress response via abscisic acid (ABA)-mediated signaling. CaDIR1
      contains a C3HC4-type RING finger domain in the N-terminal region; this domain
      functions during protein degradation via attachment of ubiquitins to the
      substrate target proteins. The expression levels of the CaDIR1 gene were
      suppressed and induced by ABA and drought treatments, respectively. We conducted
      loss-of-function and gain-of function genetic studies to examine the in vivo
      function of CaDIR1 in response to ABA and drought stress. CaDIR1-silenced pepper
      plants displayed a drought-tolerant phenotype characterized by a low level of
      transpirational water loss via increased stomatal closure and elevated leaf
      temperatures. CaDIR1-overexpressing (OX) Arabidopsis plants exhibited an ABA
      hypersensitive phenotype during the germination stage, but an ABA-hyposensitive
      phenotype-characterized by decreased stomatal closure and reduced leaf
      temperatures-at the adult stage. Moreover, adult CaDIR1-OX plants exhibited a
      drought-sensitive phenotype characterized by high levels of transpirational water
      loss. Our results indicate that CaDIR1 functions as a negative regulator of the
      drought stress response via ABA-mediated signaling. Our findings provide a
      valuable insight into the plant defense mechanism that operates during drought
      stress.

PMID- 28503187
TI  - Worker reproduction of the invasive yellow crazy ant Anoplolepis gracilipes.
AB  - BACKGROUND: Reproductive division of labor is one of the key features of social
      insects. Queens are adapted for reproduction while workers are adapted for
      foraging and colony maintenance. In many species, however, workers retain
      functional ovaries and can lay unfertilized male eggs or trophic eggs. Here we
      report for the first time on the occurrence of physogastric workers and apparent
      worker reproduction in the invasive yellow crazy ant Anoplolepis gracilipes (Fr.
      Smith). We further examined the reproductive potential and nutritional role of
      physogastric workers through multidisciplinary approaches including morphological
      characterization, laboratory manipulation, genetic analysis and behavioral
      observation. RESULTS: Egg production with two types of eggs, namely reproductive
      and trophic eggs, by physogastric workers was found. The reproductive egg was
      confirmed to be haploid and male-destined, suggesting that the workers produced
      males via arrhenotokous parthenogenesis as no spermatheca was discovered.
      Detailed observations suggested that larvae were mainly fed with trophic eggs.
      Along with consumption of trophic eggs by queens and other castes as part of
      their diet, the vital role of physogastric workers as "trophic specialist" is
      confirmed. CONCLUSION: We propose that adaptive advantages derived from worker
      reproduction for A. gracilipes may include 1) trophic eggs provisioned by
      physogastric workers likely assist colonies of A. gracilipes in overcoming
      unfavorable conditions such as paucity of food during critical founding stage; 2)
      worker-produced males are fertile and thus might offer an inclusive fitness
      advantage for the doomed orphaned colony.

PMID- 28503188
TI  - Impact of 8-week linoleic acid intake in soy oil on Lp-PLA2 activity in healthy
      adults.
AB  - BACKGROUND: No intervention follow-up study has examined the association between
      plasma n-6 polyunsaturated fatty acids (PUFAs) and lipoprotein-associated
      phospholipase A2 (Lp-PLA2), which is a risk factor for cardiovascular disease
      (CVD). We aimed to determine whether the administration of linoleic acid (LA,
      18:2n-6) in soy oil affected Lp-PLA2 activity in healthy adults. METHODS: Self
      reported healthy participants (n = 150) were randomly assigned to three groups: a
      low LA group, in which 10 mL soy oil was replaced with one apple; a medium LA
      group, in which the typical food intake was maintained; and a high LA group, in
      which 1/3 cup of cooked refined rice was replaced with 9.9 g of soy oil capsules
      daily. Plasma fatty acids and Lp-PLA2 activity were measured along with other CVD
      risk factors. RESULTS: After 8 weeks of treatment, plasma LA levels decreased in
      the low LA group and increased in the high LA group. The high LA group showed
      greater increases in apolipoprotein B (apoB) and oxidized low-density lipoprotein
      (ox-LDL) than those in the low LA group. Plasma LA levels and Lp-PLA2 activities
      demonstrated greater increases in the high LA group than those in the medium and
      low LA groups. Changes in plasma LA positively and independently correlated with
      changes in Lp-PLA2 activity, which was negatively correlated with changes in
      collagen-epinephrine closure time (CEPI-CT). CONCLUSIONS: An increase in plasma
      LA following intake of soy oil was independently associated with Lp-PLA2
      activity, which was also related to apoB, ox-LDL and CEPI-CT. TRIAL REGISTRATION:
      ClinicalTrail.gov Identifier: NCT02753907, registered 25 April 2016
      (retrospectively registered).

PMID- 28503189
TI  - Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1
      adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice.
AB  - BACKGROUND: Saturated fatty acids have been shown to cause insulin resistance and
      low-grade chronic inflammation, whereas unsaturated fatty acids suppress
      inflammation via G-protein coupled receptor 120 (GPR120) in macrophages. However,
      the anti-inflammatory effects of unsaturated fatty acids in adipocytes have yet
      to be elucidated. Hence, the aims of the present study were to evaluate the anti
      inflammatory effects of eicosapentaenoic acid (EPA) via GPR120 in adipocytes.
      METHODS: We used 250 MUM palmitate as a representative saturated fatty acid. 3T3
      L1 adipocytes were used for in vitro studies. We further evaluated the effect of
      EPA supplementation in a high-fat/high-sucrose (HFHS) diet-induced adipose tissue
      inflammatory mouse model. RESULTS: EPA attenuated palmitate-induced increases in
      inflammatory gene expression and NF-kappaB phosphorylation in 3T3-L1 adipocytes.
      Silencing of GPR120 abolished the anti-inflammatory effects of EPA. In GPR120
      downstream signal analysis, EPA was found to decrease palmitate-induced increases
      in TAK1/TAB1 complex expression. EPA supplementation suppressed HFHS-induced
      crown-like structure formation in epididymal adipose tissue and altered
      macrophage phenotypes from M1 to M2 in the stromal vascular fraction. Moreover,
      the EPA-containing diet attenuated increases in adipose p-JNK and phospho-p65 NF
      kappaB levels. CONCLUSIONS: In conclusion, the findings of the present study
      demonstrate that EPA suppresses palmitate-induced inflammation via GPR120 by
      inhibiting the TAK1/TAB1 interaction in adipocytes. EPA supplementation reduced
      HFHS diet-induced inflammatory changes in mouse adipose tissues. These results
      demonstrate adipose GPR120 as a potential therapeutic target for decreasing
      inflammation.

PMID- 28503190
TI  - Essential amino acid ingestion alters expression of genes associated with amino
      acid sensing, transport, and mTORC1 regulation in human skeletal muscle.
AB  - BACKGROUND: Amino acid availability stimulates protein synthesis via the mTORC1
      (mechanistic target of rapamycin complex 1) signaling pathway. In response to an
      increase in cellular amino acid availability, translocation of cytosolic mTORC1
      to the lysosomal surface is required to stimulate mTORC1 kinase activity.
      However, research elucidating the amino acid responsive mechanisms have thus far
      only been conducted in in vitro models. Our primary objective was to determine
      whether an increase in amino acid availability within human skeletal muscle in
      vivo would alter the expression of genes associated with amino acid sensing,
      transport and mTORC1 regulation. Our secondary objective was to determine whether
      an acute perturbation in lysosomal function would disrupt the normal pattern of
      muscle amino acid responsive gene expression. METHODS: We recruited 13 young
      adults into one of two groups: The first group ingested 10 g of essential amino
      acids (EAA). The second group ingested 10 g of EAA in the presence of chloroquine
      (CQ), a lysosomotropic agent. The subjects from each group had biopsies of the
      vastus lateralis taken before and after EAA ingestion. We determined the relative
      mRNA expression of 51 potential amino acid responsive genes using RT-qPCR.
      RESULTS: There was a differential mRNA expression for 22 genes, with 15 mRNAs
      significantly changing (P < 0.05) in response to EAA ingestion (e.g., REDD1: +209
      +/- 35%; SLC38A9: +31 +/- 9%; SLC38A10: +57 +/- 15%). In the CQ group, EAA
      ingestion resulted in a differential expression as compared to EAA alone (i.e.,
      11 out of the 22 genes were different (P < 0.05) between the two groups.).
      CONCLUSIONS: Expression of several amino acid sensing, transport, and mTORC1
      regulatory genes in human skeletal muscle are responsive to an increase in amino
      acid availability. Furthermore, potential acute disruption of lysosomal function
      by ingestion of chloroquine interferes with the normal pattern of gene expression
      following feeding. Our in vivo data in humans provide preliminary support for the
      in vitro work linking amino acid sensing pathways to mTORC1 translocation to the
      lysosome. TRIAL REGISTRATION: NCT00891696. Registered 29 April 2009.

PMID- 28503192
TI  - The Potential for Youth Programs To Promote African American Youth's Development
      of Ethnic and Racial Identity.
AB  - Effective programs for youth can reduce problem behaviors and promote positive
      development. In particular, cultural assets (e.g., ethnic-racial identity) are
      important for African American youth's health and development. In this article,
      we argue that youth programs represent an important social context for African
      American youth's development of positive ethnic-racial identity and we present a
      conceptual framework for understanding how such programs may affect African
      American youth's development in this area. Then we provide examples of evidence
      based programs that have assessed this developmental process among African
      American youth. We conclude with considerations for research.

PMID- 28503191
TI  - Breastfeeding the late preterm infant: experiences of mothers and perceptions of
      public health nurses.
AB  - BACKGROUND: The promotion and maintenance of breastfeeding with late preterm
      infants (LPIs) remain under examined topics of study. This dearth of research
      knowledge, especially for this population at-risk for various health
      complications, requires scientific investigation. In this study, we explore the
      experiences of mothers and the perceptions of public health nurses (PHNs) about
      breastfeeding late preterm infants in Calgary, Alberta, Canada. METHODS: We used
      an exploratory mixed methods design with a convenience sample of 122 mothers to
      gather quantitative data about breastfeeding. We collected qualitative data by
      means of individual face-to-face interviews with 11 mothers and 10 public health
      nurses. Data were collected from April 2013 to June 2014. We then employed an
      interpretive thematic analysis to identify central themes and relationships
      across narratives. RESULTS: We collected 74 complete data sets about
      breastfeeding. During the first 6-8 weeks postpartum, 61 mothers breastfed their
      infants.  Of these, 51 partially breastfed and 10 exclusively breastfed. For
      qualitative purposes, the researchers interviewed 11 mothers with late preterm
      babies and three themes emerged: significant difficulty with breastfeeding,
      failing to recognize the infant's feeding distress and disorganized behavior, and
      the parental stress caused by the multiple feeding issues. The public health
      nurses' comments reinforced and expanded on what the mothers reported. The themes
      for the nurses included: challenges with initiating breastfeeding, challenges
      during breastfeeding, and the need for stimulation during breastfeeding.
      CONCLUSION: Mothers face challenges when breastfeeding their late preterm infants
      and public health nurses can guide them through this experience. Families with a
      late preterm infant need to be informed about the challenges associated with
      breastfeeding a late preterm infant. It is necessary for all health care
      professionals to receive proper training on safe and effective breastfeeding of
      late preterm infants. It is essential for public health nurses to communicate
      effectively with families of late preterm infants to provide anticipatory
      guidance about potential challenges and strategies to resolve any breastfeeding
      problems.

PMID- 28503193
TI  - Correlates, comorbidities, and suicidal tendencies of problematic game use in a
      national wide sample of Korean adults.
AB  - BACKGROUND: This study aimed to investigate the prevalence, correlates,
      comorbidities, and suicidal tendencies of problematic game use in a nationally
      representative sample of Korean adults. METHODS: Of the 6022 subjects who
      participated in the 2011 Korean Epidemiologic Catchment Area study and completed
      the Composite International Diagnostic Interview 2.1, 1397 game users were
      evaluated for problematic game use using 9-item DSM-5 proposed criteria for
      Internet gaming disorder. Respondents who responded "yes" to five or more of the
      nine DSM-5 criteria were considered as problematic game users and the reminders
      were considered as normal game users. RESULTS: 4.0% (56/1397) of game users were
      classified as a problematic game user. Problematic game users were more likely to
      be in younger age group and live in urban area compared with normal game user.
      Problematic game use was positively associated with several psychiatric disorders
      including nicotine use disorder, depressive disorder, and anxiety disorder, but
      not associated with alcohol use disorder and obsessive-compulsive disorder, after
      adjusting for age, sex, and residential area. Problematic game use was
      significantly and positively associated with suicide plans, after controlling for
      psychiatric disorders as well as socio-demographic factors. CONCLUSION:
      Problematic game use is relatively prevalent in Korean adult population and
      highly comorbid with other psychiatric disorders and suicidality. Therefore,
      preventive strategy for problematic game use is needed for game users who were
      more likely to be addicted such as young adults in urban area, and mental health
      screening and appropriate treatment are needed for individuals with problematic
      game use.

PMID- 28503195
TI  - Strategies for improved isopropanol-butanol production by a Clostridium strain
      from glucose and hemicellulose through consolidated bioprocessing.
AB  - BACKGROUND: High cost of traditional substrates and formation of by-products
      (such as acetone and ethanol) in acetone-butanol-ethanol (ABE) fermentation
      hindered the large-scale production of biobutanol. Here, we comprehensively
      characterized a newly isolated solventogenic and xylanolytic Clostridium species,
      which could produce butanol at a high ratio with elimination of ethanol and
      conversion of acetone to more value-added product, isopropanol. Ultimately,
      direct butanol production from hemicellulose was achieved with efficient
      expression of indigenous xylanase by the novel strain via consolidated
      bioprocessing. RESULTS: A novel wild-type Clostridium sp. strain NJP7 was
      isolated and characterized in this study, which was capable of fermenting
      monosaccharides, e.g., glucose into butanol via a fermentative acetone
      isopropanol-butanol pathway. With enhancement of buffering capacity and alcohol
      dehydrogenase activities, butanol and isopropanol titer by Clostridium sp. strain
      NJP7 was improved to 12.21 and 1.92 g/L, respectively, and solvent productivity
      could be enhanced to 0.44 g/L/h. Furthermore, with in situ extraction with
      biodiesel, the amount of butanol and isopropanol was finally improved to 25.58
      and 5.25 g/L in the fed-batch mode. Meanwhile, Clostridium sp. strain NJP7 shows
      capability of direct isopropanol-butanol production from hemicelluloses with
      expression of indigenous xylanase. 2.06 g/L of butanol and 0.54 g/L of
      isopropanol were finally achieved through the temperature-shift simultaneous
      saccharification and fermentation, representing the highest butanol production
      directly from hemicellulose. CONCLUSION: The co-production of isopropanol with
      butanol by the newly isolated Clostridium sp. strain NJP7 would add on the
      economical values for butanol fermentation. Furthermore, the high isopropanol
      butanol production with in situ extraction would also greatly enhance the
      economic feasibility for fermentative production of butanol-isopropanol in large
      scale. Meanwhile, its direct production of butanol-isopropanol from
      polysaccharides, hemicellulose through secretion of indigenous thermostable
      xylanase, shows great potential using lignocellulosic wastes for biofuel
      production.

PMID- 28503194
TI  - What are effective strategies for implementing trauma-informed care in youth
      inpatient psychiatric and residential treatment settings? A realist systematic
      review.
AB  - BACKGROUND: Many young people who receive psychiatric care in inpatient or
      residential settings in North America have experienced various forms of emotional
      trauma. Moreover, these settings can exacerbate trauma sequelae. Common
      practices, such as seclusion and restraint, put young people at risk of
      retraumatization, development of comorbid psychopathology, injury, and even
      death. In response, psychiatric and residential facilities have embraced trauma
      informed care (TIC), an organizational change strategy which aligns service
      delivery with treatment principles and discrete interventions designed to reduce
      rates of retraumatization through responsive and non-coercive staff-client
      interactions. After more than two decades, a number of TIC frameworks and
      approaches have shown favorable results. Largely unexamined, however, are the
      features that lead to successful implementation of TIC, especially in child and
      adolescent inpatient psychiatric and residential settings. METHODS: Using methods
      proposed by Pawson et al. (J Health Serv Res Policy 10:21-34, 2005), we conducted
      a modified five-stage realist systematic review of peer-reviewed TIC literature.
      We rigorously searched ten electronic databases for peer reviewed publications
      appearing between 2000 and 2015 linking terms "trauma-informed" and "child*" or
      "youth," plus "inpatient" or "residential" plus "psych*" or "mental." After
      screening 693 unique abstracts, we selected 13 articles which described TIC
      interventions in youth psychiatric or residential settings. We designed a
      theoretically-based evaluative framework using the active implementation cycles
      of the National Implementation Research Network (NIRN) to discern which foci were
      associated with effective TIC implementation. Excluded were statewide mental
      health initiatives and TIC implementations in outpatient mental health, child
      welfare, and education settings. Interventions examined included: Attachment,
      Self-Regulation, and Competency Framework; Six Core Strategies; Collaborative
      Problem Solving; Sanctuary Model; Risking Connection; and the Fairy Tale Model.
      RESULTS: Five factors were instrumental in implementing trauma informed care
      across a spectrum of initiatives: senior leadership commitment, sufficient staff
      support, amplifying the voices of patients and families, aligning policy and
      programming with trauma informed principles, and using data to help motivate
      change. CONCLUSIONS: Reduction or elimination of coercive measures may be
      achieved by explicitly targeting specific coercive measures or by implementing
      broader therapeutic models. Additional research is needed to evaluate the
      efficacy of both approaches.

PMID- 28503196
TI  - Synthesis and analysis of separation networks for the recovery of intracellular
      chemicals generated from microbial-based conversions.
AB  - BACKGROUND: Bioseparations can contribute to more than 70% in the total
      production cost of a bio-based chemical, and if the desired chemical is localized
      intracellularly, there can be additional challenges associated with its recovery.
      Based on the properties of the desired chemical and other components in the
      stream, there can be multiple feasible options for product recovery. These
      options are composed of several alternative technologies, performing similar
      tasks. The suitability of a technology for a particular chemical depends on (1)
      its performance parameters, such as separation efficiency; (2) cost or amount of
      added separating agent; (3) properties of the bioreactor effluent (e.g., biomass
      titer, product content); and (4) final product specifications. Our goal is to
      first synthesize alternative separation options and then analyze how technology
      selection affects the overall process economics. To achieve this, we propose an
      optimization-based framework that helps in identifying the critical technologies
      and parameters. RESULTS: We study the separation networks for two representative
      classes of chemicals based on their properties. The separation network is divided
      into three stages: cell and product isolation (stage I), product concentration
      (II), and product purification and refining (III). Each stage exploits
      differences in specific product properties for achieving the desired product
      quality. The cost contribution analysis for the two cases (intracellular
      insoluble and intracellular soluble) reveals that stage I is the key cost
      contributor (>70% of the overall cost). Further analysis suggests that changes in
      input conditions and technology performance parameters lead to new designs
      primarily in stage I. CONCLUSIONS: The proposed framework provides significant
      insights for technology selection and assists in making informed decisions
      regarding technologies that should be used in combination for a given set of
      stream/product properties and final output specifications. Additionally, the
      parametric sensitivity provides an opportunity to make crucial design and
      selection decisions in a comprehensive and rational manner. This will prove
      valuable in the selection of chemicals to be produced using bioconversions
      (bioproducts) as well as in creating better bioseparation flow sheets for
      detailed economic assessment and process implementation on the commercial scale.

PMID- 28503197
TI  - The significance of proline and glutamate on butanol chaotropic stress in
      Bacillus subtilis 168.
AB  - BACKGROUND: Butanol is an intensively used industrial solvent and an attractive
      alternative biofuel, but the bioproduction suffers from its high toxicity. Among
      the native butanol producers and heterologous butanol-producing hosts, Bacillus
      subtilis 168 exhibited relatively higher butanol tolerance. Nevertheless, organic
      solvent tolerance mechanisms in Bacilli and Gram-positive bacteria have
      relatively less information. Thus, this study aimed to elucidate butanol stress
      responses that may involve in unique tolerance of B. subtilis 168 to butanol and
      other alcohol biocommodities. RESULTS: Using comparative proteomics approach and
      molecular analysis of butanol-challenged B. subtilis 168, 108 butanol-responsive
      proteins were revealed, and classified into seven groups according to their
      biological functions. While parts of them may be similar to the proteins
      reportedly involved in solvent stress response in other Gram-positive bacteria,
      significant role of proline in the proline-glutamate-arginine metabolism was
      substantiated. Detection of intracellular proline and glutamate accumulation, as
      well as glutamate transient conversion during butanol exposure confirmed their
      necessity, especially proline, for cellular butanol tolerance. Disruption of the
      particular genes in proline biosynthesis pathways clarified the essential role of
      the anabolic ProB-ProA-ProI system over the osmoadaptive ProH-ProA-ProJ system
      for cellular protection in response to butanol exposure. Molecular modifications
      to increase gene dosage for proline biosynthesis as well as for glutamate
      acquisition enhanced butanol tolerance of B. subtilis 168 up to 1.8% (vol/vol)
      under the conditions tested. CONCLUSION: This work revealed the important role of
      proline as an effective compatible solute that is required to protect cells
      against butanol chaotropic effect and to maintain cellular functions in B.
      subtilis 168 during butanol exposure. Nevertheless, the accumulation of
      intracellular proline against butanol stress required a metabolic conversion of
      glutamate through the specific biosynthetic ProB-ProA-ProI route. Thus, exogenous
      addition of glutamate, but not proline, enhanced butanol tolerance. These
      findings serve as a practical knowledge to enhance B. subtilis 168 butanol
      tolerance, and demonstrate means to engineer the bacterial host to promote higher
      butanol/alcohol tolerance of B. subtilis 168 for the production of butanol and
      other alcohol biocommodities.

PMID- 28503198
TI  - Dynamics of two methanogenic microbiomes incubated in polycyclic aromatic
      hydrocarbons, naphthenic acids, and oil field produced water.
AB  - BACKGROUND: Oil field produced water (OFPW) is widely produced in large volumes
      around the world. Transforming the organic matter in OFPW into bioenergy, such as
      biomethane, is one promising way to sustainability. However, OFPW is difficult to
      biologically degrade because it contains complex compounds such as naphthenic
      acids (NAs), or polycyclic aromatic hydrocarbons (PAHs). Although active
      microbial communities have been found in many oil reservoirs, little is known
      about how an exotic microbiome, e.g. the one which originates from municipal
      wastewater treatment plants, would evolve when incubated with OFPW. RESULTS: In
      this study, we harvested methanogenic biomass from two sources: a full-scale
      anaerobic digester (AD) treating oil and gas processing wastewater (named O&G
      sludge), and from a full-scale AD reactor treating multiple fractions of
      municipal solid wastes (named MS, short for mixed sludge). Both were incubated in
      replicate microcosms fed with PAHs, NAs, or OFPW. The results showed that the
      PAHs, NAs, and OFPW feeds could rapidly alter the methanogenic microbiomes, even
      after 14 days, while the O&G sludge adapted faster than the mixed sludge in all
      the incubations. Two rarely reported microorganisms, a hydrogenotrophic
      methanogen Candidatus methanoregula and a saccharolytic fermenter Kosmotoga, were
      found to be prevalent in the PAHs and OFPW microcosms, and are likely to play an
      important role in the syntrophic degradation of PAHs and OFPW, cooperating with
      methanogens such as Methanoregula, Methanosarcina, or Methanobacterium.
      CONCLUSIONS: The dominant phyla varied in certain patterns during the
      incubations, depending on the biomass source, feed type, and variation in
      nutrients. The sludge that originated from the oil and gas processing wastewater
      treatment (O&G) reactor adapted faster than the one from municipal solid waste
      reactors, almost certainly because the O&G biomass had been "pre-selected" by the
      environment. This study reveals the importance of biomass selection for other
      crude oil-waste-related bioengineering studies, such as bioaugmentation and
      bioremediation.

PMID- 28503199
TI  - The "Aachen fall prevention App" - a Smartphone application app for the self
      assessment of elderly patients at risk for ground level falls.
AB  - BACKGROUND: Fall incidents are a major problem for patients and healthcare. The
      "Aachen Fall Prevention App" (AFPA) represents the first mobile Health (mHealth)
      application (app) empowering older patients (persons 50+ years) to self-assess
      and monitor their individual fall risk. Self-assessment is based on the "Aachen
      Fall Prevention Scale," which consists of three steps. First, patients answer ten
      standardized yes-no questions (positive criterion >= 5 "Yes" responses). Second,
      a ten-second test of free standing without compensatory movement is performed
      (positive criterion: compensatory movement). Finally, during the third step,
      patients rate their subjective fall risk on a 10-point Likert scale, based on the
      results of steps one and two. The purpose of this app is (1) to offer a low
      threshold service through which individuals can independently monitor their
      individual fall risk and (2) to collect data about how a patient-centered mHealth
      app for fall risk assessment is used in the field. RESULTS: The results represent
      the first year of an ongoing field study. From December 2015 to December 2016,
      197 persons downloaded the AFPA (iOSTM and AndroidTM; free of charge). N = 111 of
      these persons voluntarily shared their data and thereby participated in the field
      study. Data from a final number of n = 79 persons were analyzed due to exclusion
      criteria (age, missing objective fall risk, missing self-assessment). The
      objective fall risk and the self-assessed subjective risk measured by the AFPA
      showed a significant positive relationship. CONCLUSIONS: The "Aachen Fall
      Prevention App" (AFPA) is an mHealth app released for iOS and Android. This field
      study revealed the AFPA as a promising tool to raise older adults' awareness of
      their individual fall risk by means of a low-threshold patient-driven fall risk
      assessment tool.

PMID- 28503200
TI  - A retrospective cohort study of adverse events in patients undergoing orthopaedic
      surgery.
AB  - BACKGROUND: This study's objective was to identify adverse events following
      common orthopaedic procedures, and to estimate the incidence rates and risks of
      these events and their associations with age, sex, and comorbidities. METHODS:
      This retrospective cohort study manually reviewed and extracted electronic
      medical data on the incidence and predictors of adverse events that occurred
      within 90 days of the 50 most frequent orthopaedic surgeries at an academic
      hospital in 2010. We also extracted demographic data, baseline comorbidities, and
      duration of follow-up (<=90 days). Patients were scored on the Charlson
      Comorbidity Index (CCI) and the Functional Comorbidity Index (FCI). We estimated
      incidence rates and risks for all events and associations using regression
      methods. Prolonged pain 42-days post-surgery was treated as a separate outcome.
      RESULTS: We included 1,552 patients; average age was 53.4 years, and 51.7% were
      female. A total of 1,148 adverse events were identified in 729 patients. The
      incidence rate of all adverse events was 10 events per 1,000 person-days at risk;
      47% of all patients experienced at least one adverse event within 90 days. The
      most frequent events were prolonged pain (31% of all adverse events) and
      persistent swelling (7%). We found positive associations between both comorbidity
      scores and the incidence rate and 90-day risk of all adverse events, excluding
      pain, adjusting for age and sex (neither of which was associated with adverse
      events); the association was stronger for the FCI than for the CCI. For total hip
      arthroplasty (THA) and total knee arthroplasty (TKA), the incidence rate of all
      adverse events, excluding pain, was positively associated with both comorbidity
      scores and age; the 90-day risk was positively associate with the FCI score and
      male sex. The prevalence of prolonged pain at 42 days was greater in patients
      with higher FCI scores; for THA and TKA only, pain prevalence was greater in
      those with higher FCI scores and in men. CONCLUSIONS: Adverse events are frequent
      following common orthopaedic procedures. The incidence is greatest for patients
      with more functional comorbidities. For THA and TKA procedures, being male and
      being older are also associated with a greater incidence of adverse events.

PMID- 28503201
TI  - DNA methylation and DNA methyltransferases.
AB  - The prevailing views as to the form, function, and regulation of genomic
      methylation patterns have their origin many years in the past, at a time when the
      structure of the mammalian genome was only dimly perceived, when the number of
      protein-encoding mammalian genes was believed to be at least five times greater
      than the actual number, and when it was not understood that only ~10% of the
      genome is under selective pressure and likely to have biological function. We use
      more recent findings from genome biology and whole-genome methylation profiling
      to provide a reappraisal of the shape of genomic methylation patterns and the
      nature of the changes that they undergo during gametogenesis and early
      development. We observe that the sequences that undergo deep changes in
      methylation status during early development are largely sequences without
      regulatory function. We also discuss recent findings that begin to explain the
      remarkable fidelity of maintenance methylation. Rather than a general overview of
      DNA methylation in mammals (which has been the subject of many reviews), we
      present a new analysis of the distribution of methylated CpG dinucleotides across
      the multiple sequence compartments that make up the mammalian genome, and we
      offer an updated interpretation of the nature of the changes in methylation
      patterns that occur in germ cells and early embryos. We discuss the cues that
      might designate specific sequences for demethylation or de novo methylation
      during development, and we summarize recent findings on mechanisms that maintain
      methylation patterns in mammalian genomes. We also describe the several human
      disorders, each very different from the other, that are caused by mutations in
      DNA methyltransferase genes.

PMID- 28503203
TI  - Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and
      applications.
AB  - Fluorescent carbon dots (FCDs) are an emerging class of nanomaterials made from
      carbon sources that have been hailed as potential non-toxic replacements to
      traditional semiconductor quantum dots (QDs). Particularly in the areas of live
      imaging and drug delivery, due to their water solubility, low toxicity and photo-
      and chemical stability. Carbohydrates are readily available chiral biomolecules
      in nature which offer an attractive and cheap starting material from which to
      synthesise FCDs with distinct features and interesting applications. This mini
      review article will cover the progress in the development of FCDs prepared from
      carbohydrate sources with an emphasis on their synthesis, functionalization and
      technical applications, including discussions on current challenges.

PMID- 28503202
TI  - Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in
      mouse primary T cells.
AB  - BACKGROUND: Epigenome editing is expected to manipulate transcription and cell
      fates and to elucidate the gene expression mechanisms in various cell types. For
      functional epigenome editing, assessing the chromatin context-dependent activity
      of artificial epigenetic modifier is required. RESULTS: In this study, we applied
      clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based
      epigenome editing to mouse primary T cells, focusing on the Forkhead box P3
      (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs).
      The Foxp3 gene locus is regulated by combinatorial epigenetic modifications,
      which determine the Foxp3 expression. Foxp3 expression is unstable in
      transforming growth factor beta (TGF-beta)-induced Tregs (iTregs), while stable
      in thymus-derived Tregs (tTregs). To stabilize Foxp3 expression in iTregs, we
      introduced dCas9-TET1CD (dCas9 fused to the catalytic domain (CD) of ten-eleven
      translocation dioxygenase 1 (TET1), methylcytosine dioxygenase) and dCas9-p300CD
      (dCas9 fused to the CD of p300, histone acetyltransferase) with guide RNAs
      (gRNAs) targeted to the Foxp3 gene locus. Although dCas9-TET1CD induced partial
      demethylation in enhancer region called conserved non-coding DNA sequences 2
      (CNS2), robust Foxp3 stabilization was not observed. In contrast, dCas9-p300CD
      targeted to the promoter locus partly maintained Foxp3 transcription in cultured
      and primary T cells even under inflammatory conditions in vitro. Furthermore,
      dCas9-p300CD promoted expression of Treg signature genes and enhanced suppression
      activity in vitro. CONCLUSIONS: Our results showed that artificial epigenome
      editing modified the epigenetic status and gene expression of the targeted loci,
      and engineered cellular functions in conjunction with endogenous epigenetic
      modification, suggesting effective usage of these technologies, which help
      elucidate the relationship between chromatin states and gene expression.

PMID- 28503205
TI  - Substitution of fluorine in M[C6F5BF3] with organolithium compounds: distinctions
      between O- and N-nucleophiles.
AB  - Borates M[C6F5BF3] (M = K, Li, Bu4N) react with organolithium compounds, RLi (R =
      Me, Bu, Ph), in 1,2-dimethoxyethane or diglyme to give M[4-RC6F4BF3] and M[2
      RC6F4BF3]. When R is Me or Bu, the nucleophilic substitution of the fluorine atom
      at the para position to boron is the predominant route. When R = Ph, the ratio
      M[4-RC6F4BF3]/M[2-RC6F4BF3] is ca. 1:1. Substitution of the fluorine atom at the
      ortho position to boron is solely caused by the coordination of RLi via the
      lithium atom with the fluorine atoms of the BF3 group. This differs from the
      previously reported substitution in K[C6F5BF3] by O- and N-nucleophiles that did
      not produce K[2-NuC6F4BF3].

PMID- 28503204
TI  - Ultrasound-promoted organocatalytic enamine-azide [3 + 2] cycloaddition reactions
      for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones.
AB  - The use of sonochemistry is described in the organocatalytic enamine-azide [3 +
      2] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These
      sonochemically promoted reactions were found to be amenable to a range of 1,3
      diketones or aryl azidophenyl selenides, providing an efficient access to new
      ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones in good to excellent yields
      and short reaction times. In addition, this protocol was extended to beta-keto
      esters, beta-keto amides and alpha-cyano ketones. Selanyltriazoyl carboxylates,
      carboxamides and carbonitriles were synthesized in high yields at short times of
      reaction under very mild reaction conditions.

PMID- 28503206
TI  - Inclusion complexes of beta-cyclodextrin with tricyclic drugs: an X-ray
      diffraction, NMR and molecular dynamics study.
AB  - Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion
      complexes with beta-cyclodextrin (beta-CD) in the solid state and in water
      solution. Rotating frame NOE experiments (ROESY) showed the same geometry of
      inclusion for both 1/beta-CD and 2/beta-CD complexes, with the aromatic ring
      system entering the cavity from the large rim of the cyclodextrin and the
      alkylammonium chain protruding out of the cavity and facing the secondary OH rim.
      These features matched those found in the molecular dynamics (MD) simulations in
      solution and in the solid state from single-crystal X-ray diffraction of 1/beta
      CD and 2/beta-CD complexes. The latter complex was found in a single conformation
      in the solid state, whilst the MD simulations in explicit water reproduced the
      conformational transitions observed experimentally for the free molecule.

PMID- 28503207
TI  - Membrane properties of hydroxycholesterols related to the brain cholesterol
      metabolism.
AB  - Compared to cholesterol, hydroxycholesterols contain an additional hydroxy group
      in the alkyl chain and are able to efficiently cross the brain-blood barrier.
      Therefore, they are responsible for the sterol transfer between brain and
      circulation. The current study compares the membrane properties of several
      hydroxycholesterols with those of cholesterol using 2H NMR spectroscopy, a
      membrane permeability assay, and fluorescence microscopy experiments. It is shown
      that hydroxycholesterols do not exert the unique impact on membrane properties
      characteristic for cholesterol with regard to the influence on lipid chain order,
      membrane permeability and formation of lateral domains.

PMID- 28503208
TI  - Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis
      2,3,5,6-tetrafluorocyclohexylamine motif.
AB  - This paper reports the synthesis of three amine stereoisomers 5a-c of the
      tetrafluorocyclohexyl ring system, as building blocks for discovery chemistry
      programmes. The synthesis starts from a Birch reduction of benzonitrile, followed
      by an in situ methyl iodide quench. The resultant 2,5-cyclohexadiene was
      progressed via double epoxidations and then hydrofluorination ring opening
      reactions. The resultant fluorohydrin moieties were then converted to different
      stereoisomers of the tetrafluorocyclohexyl ring system, and then reductive
      hydrogenation of the nitrile delivered three amine stereoisomers. It proved
      necessary to place a methyl group on the cyclohexane ring in order to stabilise
      the compound against subsequent HF elimination. The two all-cis
      tetrafluorocyclohexyl isomers 5a and 5b constitute facially polarized cyclohexane
      rings, with fluorines on the electronegative face and hydrogens on the
      electropositive face.

PMID- 28503209
TI  - Continuous-flow processes for the catalytic partial hydrogenation reaction of
      alkynes.
AB  - The catalytic partial hydrogenation of substituted alkynes to alkenes is a
      process of high importance in the manufacture of several market chemicals. The
      present paper shortly reviews the heterogeneous catalytic systems engineered for
      this reaction under continuous flow and in the liquid phase. The main
      contributions appeared in the literature from 1997 up to August 2016 are
      discussed in terms of reactor design. A comparison with batch and industrial
      processes is provided whenever possible.

PMID- 28503210
TI  - Synthesis of ribavirin 2'-Me-C-nucleoside analogues.
AB  - An efficient synthetic pathway leading to two carbonated analogues of ribavirin
      is described. The key-steps in the synthesis of these ribosyltriazoles bearing a
      quaternary carbon atom in the 2'-position are an indium-mediated alkynylation and
      a 1,3-dipolar cyclization.

PMID- 28503211
TI  - Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel
      mouse and human analysis.
AB  - BACKGROUND: Clinicians have qualitatively described rhythmic delta activity as a
      prominent EEG abnormality in individuals with Angelman syndrome, but this
      phenotype has yet to be rigorously quantified in the clinical population or
      validated in a preclinical model. Here, we sought to quantitatively measure delta
      rhythmicity and evaluate its fidelity as a biomarker. METHODS: We quantified
      delta oscillations in mouse and human using parallel spectral analysis methods
      and measured regional, state-specific, and developmental changes in delta rhythms
      in a patient population. RESULTS: Delta power was broadly increased and more
      dynamic in both the Angelman syndrome mouse model, relative to wild-type
      littermates, and in children with Angelman syndrome, relative to age-matched
      neurotypical controls. Enhanced delta oscillations in children with Angelman
      syndrome were present during wakefulness and sleep, were generalized across the
      neocortex, and were more pronounced at earlier ages. CONCLUSIONS: Delta
      rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in
      both preclinical and clinical settings.

PMID- 28503213
TI  - Epigenetic modifications of the immune-checkpoint genes CTLA4 and PDCD1 in non
      small cell lung cancer results in increased expression.
AB  - Targeting checkpoint inhibitors using monoclonal antibodies results in
      significantly better outcome of cancer patients compared to conventional
      chemotherapy. However, the current companion diagnostics to predict response is
      so far suboptimal, since they base on more or less reliable immunohistochemical
      approaches. In order to overcome these limitations, we analyzed epigenetic
      modifications of PDCD1 (PD1), CD274 (PD-L1), and CTLA4 in NSCLC tissues from 39
      patients. Results were correlated with transcriptome data. Significant
      differences in the CpG-methylation patterns between tumor tissues and matched
      controls were observed for CTLA4 and PDCD1 (PD1) showing a decreased methylation
      of these genes compared to matched tumor-free tissues from the same patients.
      Results were confirmed by bisulfide sequencing in an independent validation
      cohort. Hypomethylation also resulted in increased expression of these genes as
      shown by transcriptome data. These epigenetic pathways as a hallmark of NSCLC
      might be useful to generate more precise diagnostic approaches in the future.

PMID- 28503215
TI  - Fast determination of structurally cohesive subgroups in large networks.
AB  - Structurally cohesive subgroups are a powerful and mathematically rigorous way to
      characterize network robustness. Their strength lies in the ability to detect
      strong connections among vertices that not only have no neighbors in common, but
      that may be distantly separated in the graph. Unfortunately, identifying cohesive
      subgroups is a computationally intensive problem, which has limited empirical
      assessments of cohesion to relatively small graphs of at most a few thousand
      vertices. We describe here an approach that exploits the properties of cliques, k
      cores and vertex separators to iteratively reduce the complexity of the graph to
      the point where standard algorithms can be used to complete the analysis. As a
      proof of principle, we apply our method to the cohesion analysis of a 29,462
      vertex biconnected component extracted from a 128,151-vertex co-authorship data
      set.

PMID- 28503212
TI  - Associations between maternal risk factors of adverse pregnancy and birth
      outcomes and the offspring epigenetic clock of gestational age at birth.
AB  - BACKGROUND: A recent study has shown that it is possible to accurately estimate
      gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical
      cord blood/newborn blood spots. This DNAm GA predictor may provide additional
      information relevant to developmental stage. In 814 mother-neonate pairs, we
      evaluated the associations between DNAm GA and a number of maternal and offspring
      characteristics. These characteristics reflect prenatal environmental adversity
      and are expected to influence newborn developmental stage. RESULTS: DNAm GA
      acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at
      birth was associated with maternal age of over 40 years at delivery, pre
      eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and
      treatment with antenatal betamethasone in the index pregnancy, lower neonatal
      birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD;
      i.e., younger DNAm GA than chronological GA) of the offspring at birth was
      associated with insulin-treated gestational diabetes mellitus (GDM) in a previous
      pregnancy and Sjogren's syndrome. These findings were more accentuated when the
      DNAm GA calculation was based on the raw difference between DNAm GA and GA than
      on the residual from the linear regression of DNAm GA on GA. CONCLUSIONS: Our
      findings show that variations in the DNAm GA of the offspring at birth are
      associated with a number of maternal and offspring characteristics known to
      reflect exposure to prenatal environmental adversity. Future studies should be
      aimed at determining if this biological variation is predictive of developmental
      adversity.

PMID- 28503216
TI  - Public knowledge, attitudes and practices regarding antibiotic use in Kosovo.
AB  - BACKGROUND: Antimicrobial resistance is becoming a major public health challenge
      worldwide, caused primarily by the misuse of antibiotics. Antibiotic use is
      closely related to the knowledge, attitudes and behaviour of a population.
      OBJECTIVE: The objective of this study was to assess the level of knowledge,
      attitudes and practices about antibiotic use among the general public in Kosovo.
      METHODS: A cross-sectional face-to-face survey was carried out with a sample of
      811 randomly selected Kosovo residents. The methodology used for this survey was
      based on the European Commission Eurobarometer survey on antimicrobial
      resistance. RESULTS: More than half of respondents (58.7%) have used antibiotics
      during the past year. A quarter of respondents consumed antibiotics without a
      medical prescription. The most common reasons for usage were flu (23.8%),
      followed by sore throat (20.2%), cold (13%) and common cold (7.6%). 42.5% of
      respondents think that antibiotics are effective against viral infections. Almost
      half of respondents (46.7%) received information about the unnecessary use of
      antibiotics and 32.5% of them report having changed their views and behaviours
      after receiving this information. Health care workers were identified as the most
      trustworthy source of information on antibiotic use (67.2%). CONCLUSION: These
      results provide quantitative baseline data on Kosovar knowledge, attitudes and
      practice regarding the use of antibiotic. These findings have potential to
      empower educational campaigns to promote the prudent use of antibiotics in both
      community and health care settings.

PMID- 28503217
TI  - Assessment and use of drug information references in Utah pharmacies.
AB  - OBJECTIVE: To determine which drug references Utah pharmacists use most
      frequently. To determine which types of drug information questions are most
      commonly asked, and whether Utah pharmacists have access to adequate references
      to respond to these questions. METHODS: A 19-question survey was created using
      Qualtrics, LLC (Provo, Utah) software. An electronic survey link was sent to
      1,431 pharmacists with a valid e-mail address listed in the Department of
      Professional Licensing database. Questions focused on available references in the
      participant's pharmacy, how current the references are, and the participant's use
      of the references. Surveys were analyzed for participants practicing in either
      community or hospital pharmacies in the state of Utah. RESULTS: A total of 147
      responses were included in the analysis. Approximately 44% of respondents
      practiced in the community, and 56% practiced in a hospital setting. The most
      commonly used references by Utah pharmacists are Micromedex, Lexicomp, UpToDate,
      Clinical Pharmacology, and Drug Facts & Comparisons. Pharmacists in the community
      frequently receive questions related to adverse drug reactions, drug
      interactions, and over-the-counter medications. Pharmacists in the hospital
      frequently receive questions relating to dosage and administration, drug
      interactions, and adverse drug reactions. About 89% of community pharmacists and
      96% of hospital pharmacists feel available references are adequate to answer the
      questions they receive. CONCLUSIONS: Utah pharmacists generally use large
      reference suites to answer drug information questions. The majority of
      pharmacists consider the references available to them to be adequate to answer
      the questions they receive.

PMID- 28503214
TI  - Management of Resistant, Atypical and Culture-negative Periprosthetic Joint
      Infections after Hip and Knee Arthroplasty.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication
      following lower extremity total joint arthroplasty (TJA). It is a leading cause
      of morbidity and revision following TJA. As such, PJI is a significant driver of
      healthcare costs. The prevalence of PJI related to resistant and atypical
      organisms is increasing, and approximately 10-30% of PJIs are culture-negative.
      The purpose of this review is to summarize the current epidemiology, diagnostics,
      and management of PJI associated with resistant and atypical pathogens and of
      culture-negative PJIs. METHODS: The published literature related to the
      epidemiology, diagnosis, and management of atypical, drug-resistant, and culture
      negative PJI is reviewed. RESULTS: The clinical diagnosis of PJI is often
      challenging, particularly when pathogens are fastidious or when antibiotics have
      been administered empirically. Molecular diagnostic studies, such as synovial
      alpha-defensin, may provide rapid, accurate identification of PJI, even in the
      setting of concurrent antibiotics administration or systemic inflammatory
      disease. Once PJI is diagnosed, two-stage exchange arthroplasty remains the gold
      standard for treating PJI with resistant microorganisms, since there is a high
      rate of treatment failure with irrigation and debridement and with one-stage
      exchange arthroplasty. CONCLUSION: Additional research is needed to define the
      optimal treatment of PJIs associated with rare pathogens, such as fungi and
      mycobacteria. There is a need for inexpensive, reliable tests that rapidly detect
      specific microbial species and antimicrobial susceptibilities. Additional
      research is also required to define the specific organisms, clinical scenarios,
      surgical techniques, and antimicrobial regimens that allow for reproducible
      treatment success with prosthetic retention strategies.

PMID- 28503218
TI  - Impact of value added services on patient waiting time at the ambulatory pharmacy
      Queen Elizabeth Hospital.
AB  - BACKGROUND: Value added services (VAS) are an innovative dispensing system
      created to provide an alternative means of collecting partial drug supply from
      our hospital. This in turn was projected to reduce the necessity for patient to
      visit pharmacy counter and thus reduce the burden of prescription handling.
      OBJECTIVE: To evaluate the impact of increased VAS uptake following promotional
      campaign towards patient waiting time and to explore factors that may affect
      patient waiting time at the Ambulatory Pharmacy, Queen Elizabeth Hospital.
      METHODS: A quasi experimental study design was conducted from September 2014 till
      June 2015 at the Ambulatory Pharmacy. During pre-intervention phase, baseline
      parameters were collected retrospectively. Then, VAS promotional campaign was
      carried out for six months and whilst this was done, the primary outcome of
      patient waiting time was measured by percentage of prescription served less than
      30 minutes. A linear regression analysis was used to determine the impact of
      increased VAS uptake towards patient waiting time. RESULTS: An increased in
      percentage of VAS registration (20.9% vs 35.7%, p<0.001) was observed after the
      promotional campaign. The mean percentage of prescription served less than 30
      minutes increased from 83.2% SD=15.9 to 90.3% SD=11.5, p=0.001. After controlling
      for covariates, it was found that patient waiting time was affected by number of
      pharmacy technicians (b=-0.0349, 95%CI-0.0548 : -0.0150, p=0.001), number of
      pharmacy counters (b=0.1125, 95%CI 0.0631 : 0.1620, p<0.001), number of
      prescriptions (b=0.0008, 95%CI 0.0004 : 0.0011, p<0.001), and number of refill
      prescriptions (b=0.0004, 95%CI 0.0002 : 0.0007, p<0.001). The increased in
      percentage of VAS registration was associated with reduction in number of refill
      prescription (b=-2.9838, 95%CI -4.2289 : -1.7388, p<0.001). CONCLUSIONS: Patient
      waiting time at the Ambulatory Pharmacy improved with the increased in VAS
      registration. The impact of increased VAS uptake on patient waiting time resulted
      from reduction in refill prescriptions. Patient waiting time is influenced by
      number of pharmacy technicians, number of pharmacy counters, number of
      prescriptions and number of refill prescriptions.

PMID- 28503219
TI  - Situation analysis of community pharmacy owners in Lebanon.
AB  - OBJECTIVE: To evaluate the current community pharmacists' interventions and job
      satisfaction, secondary to the alteration in the financial rewards. METHODS: A
      cross-sectional study was carried out, using a proportionate random sample of
      Lebanese community pharmacy owners from all districts of Lebanon. RESULTS: Out of
      1618 distributed questionnaires, 1465 (90.5%) were collected back from pharmacy
      owners. Our study results showed that the monthly sales and profit decreased
      significantly in the last decade as well as the number of loyal customers
      (p<0.001 for all). The rent, the total assistant pharmacists' and employees'
      salaries, income taxes, municipality fees, the total bills (electricity, water,
      cleaning, security) and the disposal of expired products per year significantly
      increased during the last 10 years (p<0.001). 95% of the owners said they cannot
      afford to hire any more pharmacists while 45% said they cannot afford buying
      software for their pharmacies. Finally, 89% of these owners admitted that their
      situation was better 10 years ago compared to nowadays. CONCLUSION: Most Lebanese
      community pharmacists are not financially satisfied; their financial situation
      deteriorated in the last decade. The ministry of Health along with the Order of
      Pharmacists in Lebanon should cooperate together to resolve this problem since
      they are two entities responsible for the patient's health.

PMID- 28503220
TI  - Medication reconciliation errors in a tertiary care hospital in Saudi Arabia:
      admission discrepancies and risk factors.
AB  - BACKGROUND: Medication reconciliation is a major component of safe patient care.
      One of the main problems in the implementation of a medication reconciliation
      process is the lack of human resources. With limited resources, it is better to
      target medication reconciliation resources to patients who will derive the most
      benefit from it. OBJECTIVE: The primary objective of this study was to determine
      the frequency and types of medication reconciliation errors identified by
      pharmacists performing medication reconciliation at admission. Each medication
      error was rated for its potential to cause patient harm during hospitalization. A
      secondary objective was to determine risk factors associated with medication
      reconciliation errors. METHODS: This was a prospective, single-center pilot study
      conducted in the internal medicine and surgical wards of a tertiary care teaching
      hospital in the Eastern province of Saudi Arabia. A clinical pharmacist took the
      best possible medication history of patients admitted to medical and surgical
      services and compared with the medication orders at hospital admission; any
      identified discrepancies were noted and analyzed for reconciliation errors.
      Multivariate logistic regression was performed to determine the risk factors
      related to reconciliation errors. RESULTS: A total of 328 patients (138 in
      surgical and 198 in medical) were included in the study. For the 1419 medications
      recorded, 1091 discrepancies were discovered out of which 491 (41.6%) were
      reconciliation errors. The errors affected 177 patients (54%). The incidence of
      reconciliation errors in the medical patient group was 25.1% and 32.0% in the
      surgical group (p<0.001). In both groups, the most frequent reconciliation error
      was the omission (43.5% and 51.2%). Lipid-lowering (12.4%) and antihypertensive
      agents were most commonly involved. If undetected, 43.6% of order errors were
      rated as potentially requiring increased monitoring or intervention to preclude
      harm; 17.7% were rated as potentially harmful. A multivariate logistic regression
      model showed that patients aged >=65 years, polypharmacy, and prescriptions for
      hypoglycemic drugs and warfarin were more likely associated with reconciliation
      errors. CONCLUSION: There is a high failure rate in medication reconciliation
      process in patients admitted to the medical and surgical department. The
      reconciliation process proves to be a useful tool since nearly half of avoided
      reconciliation errors were unintentional and had the potential for harm. This
      strategy, based on our results and the difficulty of applying the process to all
      patients should be directed primarily to the patients at increased risk of error.

PMID- 28503221
TI  - Management of musculoskeletal pain in retail drug outlets within a Nigerian
      community: a descriptive study.
AB  - OBJECTIVE: This work aimed to describe attitudes and practices of both community
      pharmacies and patent and proprietary medicine vendor (PPMV) outlets towards over
      the-counter (OTC) analgesic use for musculoskeletal pain states within Zaria,
      Nigeria. METHODS: The study was carried out in 2 phases from May to August 2016.
      Phase one was a cross-sectional survey of 40 retail drug outlets (10 community
      pharmacies and 30 PPMVs). A simulated patient scenario of a young adult male
      complaining of acute onset back pain was used to collect data on the type and
      quality of analgesic recommended, duration of consultation, as well as nature of
      information provided during the drug dispensing process. The second phase
      involved semi structured interviews with 7 drug vendors (4 pharmacists and 3
      patent medicine vendors). The interviewees were asked questions to assess their
      knowledge of analgesics as well as what type of analgesic they would recommend in
      three hypothetical patient scenarios. RESULTS: A wide variety of therapeutic
      agents were recommended for the simulated patient. Majority of these drugs were
      oral analgesics and contained NSAIDS either alone or in combination. Less than
      half of both patent medicine outlets and pharmacies (26.7% and 40% respectively)
      provided the simulated patient with information on duration of therapy, and asked
      the patient questions about their past medical and medication history (30% and
      33.3% respectively). All analgesics purchased from the pharmacies were registered
      with the Nigerian drug regulatory agency and had expiry dates compared to only
      66.7% and 90% of those bought from patent medicine outlets. Interviewed drug
      vendors admitted to obtaining a large amount of their knowledge on analgesics
      from drug information leaflets and prior learning. They also showed some
      knowledge deficits when questioned on side effects of analgesics and appropriate
      drug selection in the hypothetical scenarios. CONCLUSIONS: There are problems
      with both the OTC analgesics recommended, and the counselling provided for these
      medicines by drug vendors within the Zaria community. While both pharmacies and
      patent medicine outlets had shortcomings in several of the areas assessed by the
      simulated patient, the pharmacies performed better.

PMID- 28503222
TI  - Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and
      meta-analysis.
AB  - BACKGROUND: Chemotherapy induced nausea and vomiting (CINV) remains the most
      distressing event in patients receiving highly emetogenic chemotherapy (HEC) or
      moderately emetogenic chemotherapy (MEC). OBJECTIVE: Therefore, this meta
      analysis was conducted to evaluate the efficacy of olanzapine containing regimen
      in preventing acute, delayed and overall phases of CINV. METHODS: PubMed, EBSCO,
      and Cochrane central register of controlled trials electronic databases were
      searched to identify RCTs that compared the effects of olanzapine with non
      olanzapine regimen in preventing CINV. Randomized clinical trials (RCTs) that
      compared olanzapine containing regimen with non-olanzapine regimen were included.
      The primary outcomes were the percentage of patients achieving no vomiting or no
      nausea in acute, delayed and overall phases. RESULTS: 13 RCTs that enrolled 1686
      participants were included in this meta-analysis. 852 patients were assigned to
      olanzapine and 834 patients were assigned to non-olanzapine regimen (other
      standard antiemetic regimen). The percentages of no emesis achieved were 87.5%,
      76.2%, 73.6% in olanzapine versus 76.7%, 61.8%, and 56.4% in non-olanzapine
      regimen in acute, delayed and overall phases, respectively. The percentages of no
      nausea were 82%, 64.3%, 61.6% in olanzapine group versus 71.3%, 41.8%, and 40.6%
      in non-olanzapine group in acute, delayed and overall phases, respectively. In
      general, olanzapine containing regimen achieved statistical superiority to non
      olanzapine regimen in no vomiting endpoint in acute phase (OR 2.16; 95%CI 1.60 to
      2.91, p<0.00001; I-square=5%; p=0.40), delayed phase (OR 2.28; 95%CI 1.1.46 to
      3.54, p=0.0003; I-square=65%; p=0.001) and overall phase (OR 2.48; 95%CI 1.59 to
      3.86, p<0.0001; I-square=69%; p< 0.0001). CONCLUSION: The current meta-analysis
      showed that olanzapine was statistically and clinically superior to non
      olanzapine regimen in preventing CINV in most domains of the parameters.

PMID- 28503223
TI  - Hospital and community pharmacists' perception of the scope, barriers and
      challenges of pharmacy practice-based research in Nigeria.
AB  - OBJECTIVES: To evaluate perception, extent of involvement and barriers to
      pharmacy practice-based research among community and hospital pharmacists in
      Ibadan, Oyo state, southwestern Nigeria. METHODS: A prospective cross-sectional
      study was carried out among 65 hospital and 86 community pharmacists with at
      least five-year post-qualification experience, using pre-tested questionnaire.
      Socio-demographic information, extent of involvement, relevance and scope, as
      well as barriers to pharmacy practice-based research were explored. Data were
      summarised using descriptive statistics. Kruskal-Wallis and Mann-Whitney-U tests
      were used for evaluating ranked variables at p<0.05. RESULTS: Nearly all
      participants (>95.0%) in each practice category agreed that pharmacy practice
      based research is essential to pharmacy profession. Greater than 90.0% agreed
      that pharmacy practice-based research may help in identifying gaps to improve
      practice. Thirty-five (40.7%) community and 36(55.4%) hospital pharmacist
      participants had previously involved in practice-based research. Seventy-seven
      (89.5%) community and 55(84.3%) hospital pharmacists agreed that acquisition of
      additional research-oriented training is essential for effective conduct of
      pharmacy practice-based research. More than one-half in each category agreed that
      inadequate financial commitment and lack of access to patient's data are major
      barriers to pharmacy practice-based research. CONCLUSIONS: Community and hospital
      pharmacists agreed that pharmacy practice based research is essential to pharmacy
      profession, especially in identifying areas of focus to improve practice.
      Necessity for acquiring additional training in research, financial constraints
      and lack of access to patient's data were identified as barriers to pharmacy
      practice-based research. Thus, there is a need to continually stimulate
      pharmacists' interest in research so as to enhance professional competence and
      promote healthcare development.

PMID- 28503224
TI  - Psychometric properties of the Belief about Medicines Questionnaire (BMQ) in the
      Maltese language.
AB  - BACKGROUND: Investigating beliefs about medicines has been of interest over the
      past years, with studies aiming to better understand theoretical reasons behind
      development of such beliefs. OBJECTIVE: This study aimed to produce a culturally
      and contextually appropriate version of the Beliefs about Medicines Questionnaire
      (BMQ) in the Maltese language and to assess its psychometric properties. METHODS:
      Medication beliefs were evaluated using the BMQ which is divided into two
      sections: BMQ-General (sub-scales: Overuse and Harm, 4 items per sub-scale) and
      BMQ-Specific (sub-scales: Necessity and Concerns, 5 items per sub-scale).
      Following translation/back translation, the Maltese version of the BMQ was
      applied to patients having asthma, diabetes, cardiovascular disease or depression
      who attended out-patients' clinics at the main state general hospital in Malta
      between June and September 2013. Cronbach's alpha coefficient, alpha, was used to
      determine internal consistency of the BMQ and Principal Component Analysis using
      Varimax rotation with Kaiser normalisation was carried out to analyse component
      loading of the items on the respective sub-scales. RESULTS: The Maltese version
      of the BMQ showed acceptable internal consistency for the harm scale
      (alpha=0.56), the necessity scale (alpha=0.73) and the concerns scale
      (alpha=0.66), however the overuse scale gave poor internal consistency
      (alpha=0.48) due to the item on natural remedies which posed some difficulty in
      the Maltese sample. The final solution for Principal Component Analysis yielded a
      four-factor structure representing the 4 sub-scales of the BMQ, with results
      being comparable to previous studies out in different languages. CONCLUSION: The
      Maltese version of the BMQ was found to have acceptable psychometric properties
      for the beliefs about medicines in the Maltese population.

PMID- 28503225
TI  - Self-reported and actual involvement of community pharmacists in patient
      counseling: a cross-sectional and simulated patient study in Gondar, Ethiopia.
AB  - BACKGROUND: Community pharmacists play a crucial role in reducing medication
      related health problems and improving the patient's overall wellbeing. Evidence
      suggests that community pharmacist led counseling services result in a better
      clinical and self-reported outcome, including a higher level of satisfaction and
      quality of life. OBJECTIVE: This study aims to document self-reported and actual
      levels of community pharmacists' involvement in the provision of patient
      counseling and barriers that limit their involvement in such services. METHODS:
      Simulated patient visits and a cross-sectional survey of community pharmacists
      were employed in Gondar town, Ethiopia between March 15 and May 15, 2016 to
      observe actual counseling practices and to assess their reported counseling
      practices respectively. Four different scenarios were developed for the simulated
      patient visit. A well designed questionnaire and an assessment form were used for
      the survey and simulated patient visit. RESULTS: In the cross-sectional survey,
      84 pharmacists were approached and 78 agreed to participate (92.8 % response
      rate). Of the respondents, 96.1% agreed/strongly agreed that patient counseling
      is important and 69.3% strongly agreed that patient counseling should be a
      professional duty. The most frequent information provided to patients were dosing
      schedule of drugs, how to take medication, and drug-food interaction. Majority of
      community pharmacists either strongly agreed (42.1%) or agreed (51.3%) that
      patients are comfortable towards their counseling practice. A total of 48
      simulated visits were conducted and a medicine was dispensed in all visits. In
      all four scenarios, dosage schedule (100%), how to take medication (97.6%) and
      drug-food interaction (69.1%) were the most common type of information provided
      while what to do when dose is missed (100%), contraindication (95.2%) and the
      importance of compliance or adherence (92.9%) were the most commonly ignored
      types of information. CONCLUSIONS: The present study emphasizes the existing gap
      in self-reported and actual counseling practices by community pharmacist in
      Gondar town, Ethiopia. Hence, the ministry of health, local health policy makers
      and other stakeholders should collaborate to design interventions to improve
      community pharmacists' dispensing and counseling practice.

PMID- 28503226
TI  - Consumer views on safety of over-the-counter drugs, preferred retailers and
      information sources in Sweden: after re-regulation of the pharmacy market.
AB  - BACKGROUND: The availability of over-the-counter drugs (OTCs) has increased in
      Sweden since a re-regulation of the pharmacy market in 2009, through which non
      pharmacy retailers became permitted to provide certain OTCs. OBJECTIVE: To
      examine the adult general public's views on safety, purchasing and information
      channels, storage and disposal of OTCs in Sweden, three years after the re
      regulation of the pharmacy market. METHODS: A questionnaire study in 2012-13 in a
      stratified, random sample of all inhabitants in Sweden >= 18 years old. RESULTS:
      Totally 8,302 people (42%) answered the questionnaire. Seven percent found OTCs
      completely harmless regardless of how they are being used, 18% felt they should
      be used only on health professionals' recommendation. Differences in how OTCs are
      perceived were however found with regards to respondents' country of birth,
      family type, educational level and income. The pharmacy was still the preferred
      OTC drug retailer by 83% of the respondents and preferred information source by
      80% Reasons for preferred retailers were primarily due to out of habit (45%),
      counseling provided (35%), the product range (34%) and the confidence in staff
      (27%). Analgesics are the most common OTCs to have at home (90%). The bathroom
      cabinet is the primary site for storage (42%) and 16% throw their OTC leftovers
      in the trash. CONCLUSIONS: The study population does not consider OTCs as
      harmless regardless of how they are used, but on the other hand feels they should
      not be taken on health professionals' recommendation only. The pharmacy is still
      the preferred retailer and information source, and there is room for further
      improvement in the storage and disposal of OTCs. A return of OTC drug leftovers
      to the pharmacy should be further encouraged. Due to several limitations, great
      caution should however be observed when generalizing the results to the adult
      population of Sweden.

PMID- 28503227
TI  - Relationship between pharmacy residency examination rank and specialty choice for
      French pharmacy residency-admitted students.
AB  - OBJECTIVE: To analyze the link between the rank at the national pharmacy
      residency examination and the choice of pharmacy specialty for hospital residency
      admitted French pharmacy students. METHODS: Examination ranks as well as the
      pharmacy residency specialty to which residency candidates are finally admitted
      were collected for all students (n=1948) having successfully passed the national
      French pharmacy residency examination over the period 2013-2016. Students were
      categorized by their pharmacy specialty for residency, i.e., "Medical Biology"
      (n=591), "Hospital Pharmacy" (n=1175) and "Pharmaceutical Innovation and
      Research" (n=182), and medians of examination ranks as well as limit ranks (the
      rank of the last admitted postulant) by specialty were compared. RESULTS:
      Examination ranks for pharmacy residency-admitted students were found to
      significantly differ according to the nature of the specialty in which students
      were finally admitted. "Medical Biology" has the lowest examination ranks (and
      appears thus as the most selective specialty), followed by "Hospital Pharmacy"
      and ended by "Pharmaceutical Innovation and Research", that has the highest
      examination ranks (and appears thus as the least selective specialty). Limit
      examination ranks were additionally shown to discriminate university hospitals in
      which residents were assigned. CONCLUSION: Specialty choice for hospital
      residency-admitted French pharmacy candidates is closely associated with their
      rank at the national pharmacy residency examination, which can be assumed as
      reflecting their academic level. By this way, an implicit hierarchy of French
      pharmacy residency specialties according to the academic level of postulants can
      likely be drawn.

PMID- 28503228
TI  - Network meta-analysis: a technique to gather evidence from direct and indirect
      comparisons.
AB  - Systematic reviews and pairwise meta-analyses of randomized controlled trials, at
      the intersection of clinical medicine, epidemiology and statistics, are
      positioned at the top of evidence-based practice hierarchy. These are important
      tools to base drugs approval, clinical protocols and guidelines formulation and
      for decision-making. However, this traditional technique only partially yield
      information that clinicians, patients and policy-makers need to make informed
      decisions, since it usually compares only two interventions at the time. In the
      market, regardless the clinical condition under evaluation, usually many
      interventions are available and few of them have been studied in head-to-head
      studies. This scenario precludes conclusions to be drawn from comparisons of all
      interventions profile (e.g. efficacy and safety). The recent development and
      introduction of a new technique - usually referred as network meta-analysis,
      indirect meta-analysis, multiple or mixed treatment comparisons - has allowed the
      estimation of metrics for all possible comparisons in the same model,
      simultaneously gathering direct and indirect evidence. Over the last years this
      statistical tool has matured as technique with models available for all types of
      raw data, producing different pooled effect measures, using both Frequentist and
      Bayesian frameworks, with different software packages. However, the conduction,
      report and interpretation of network meta-analysis still poses multiple
      challenges that should be carefully considered, especially because this technique
      inherits all assumptions from pairwise meta-analysis but with increased
      complexity. Thus, we aim to provide a basic explanation of network meta-analysis
      conduction, highlighting its risks and benefits for evidence-based practice,
      including information on statistical methods evolution, assumptions and steps for
      performing the analysis.

PMID- 28503230
TI  - Utility of preoperative 3 Tesla pelvic phased-array multiparametric magnetic
      resonance imaging in prediction of extracapsular extension and seminal vesicle
      invasion of prostate cancer and its impact on surgical margin status: Experience
      at a Canadian academic tertiary care centre.
AB  - INTRODUCTION: To evaluate the utility of 3 Tesla (3T) pelvic phased-array (PPA)
      multiparametric magnetic resonance imaging (mpMRI) to predict extracapsular
      extension (ECE) and seminal vesicle invasion (SVI) and its subsequent effect on
      radical prostatectomy (RP) surgical margin status. METHODS: A retrospective
      evaluation was conducted of RP patients who underwent preoperative 3T PPA mpMRI
      (without endorectal coil) based on clinical probability of adverse pathological
      features. Frequencies, specificity, sensitivity, positive predictive value (PPV),
      and negative predictive value (NPV) of mpMRI in predicting the status of ECE and
      SVI were calculated. RESULTS: Forty-eight consecutive patients were included.
      Sensitivity, specificity, PPV, and NPV for 3T PPA mpMRI using T2-weighted
      sequences with diffusion-weighted imaging (DWI) and dynamic contrast enhanced
      (DCE) imaging to predict ECE was 39%, 56%, 45%, and 50%, respectively, while SVI
      prediction was 33%, 95%, 50%, and 91%, respectively. Twelve of the 28 cases
      predicted as being negative for ECE had positive margins, while two of the 20
      cases predicted to be positive for ECE had positive margins. Imaging predicted
      four cases would have SVI, yet two had positive margins, while of the 44 cases
      predicted as being negative for SVI, four had positive margins. CONCLUSIONS:
      These findings at our centre suggest that the use of 3T PPA mpMRI using T2
      weighted sequences with DWI and DCE in predicting pathological ECE and SVI is of
      questionable benefit. These mpMRI reports may result in closer dissection of
      neurovascular bundles and subsequent positive surgical margins. Caution should be
      exercised when basing intraoperative decisions on mpMRI findings.

PMID- 28503231
TI  - OnabotulinumtoxinA for the treatment of idiopathic overactive bladder is
      effective and safe for repeated use.
AB  - INTRODUCTION: The objective of this study was to compare efficacy and safety
      outcomes between patients receiving onabotulinum-toxinA (OnabotA) for the first
      time and those receiving a repeat injection. METHODS: Data collected before and
      after OnabotA injection were extracted from a clinical registry. Patients were
      classified into either first or repeat injection subgroups. Efficacy was measured
      by the change in use of oral bladder medications, the number of voids per day or
      night, the frequency of urinary incontinence (UI) episodes, and patient-reported
      outcomes. Safety was measured by the number of self-reported complications.
      Differences in safety measures between the subgroups were tested. RESULTS: The
      analysis included complete data from 81 patients; 30 (37%) receiving OnabotA for
      the first time, 51 (63%) receiving a repeat injection. Both subgroups reported
      significant reductions in the use of anticholinergics, more tolerable bladder
      symptoms, and improvements in patient-reported outcomes. Dry rates were similarly
      high in both groups (50% and 43%, respectively). There were no statistically
      significant differences between the subgroups in terms of their safety outcomes.
      CONCLUSIONS: OnabotA is equally as efficacious and safe for patients with
      overactive bladder receiving a repeat injection as it is for those receiving
      their first injection.

PMID- 28503232
TI  - Cytoreductive nephrectomy in the modern era: Predictors of use, morbidity, and
      survival.
AB  - INTRODUCTION: To determine tumour, patient, and provider factors associated with
      cytoreductive nephrectomy (CN) use and to identify those factors that predicted
      short-term and long-term surgical outcomes. METHODS: We performed a retrospective
      review (1998-2011) of the National Cancer Database, a U.S. population-based
      oncology outcomes database. The review included 36 549 patients with metastatic
      renal cell carcinoma (mRCC). We assessed predictors of CN use, length of stay
      (LOS), 30-day readmission, and 30-day mortality using multivariable logistic
      regression. The Cox proportional hazards model assessed predictors of overall
      survival (OS). RESULTS: Overall, 10 809 (29.6%) patients received CN, increasing
      from 15.2% to 36.1% over time. Private insurance (odds ratio [OR] 1.26; 95%
      confidence interval [CI] 1.16-1.37) and academic facilities (OR 1.83; 95% CI 1.68
      1.99) were associated with receiving CN (p<0.0001). Charlson score >=2 and older
      age group were less likely to undergo surgery (p<0.0001). Median LOS was five
      days (inter-quartile range [IQR] 3-7), while 30-day readmission and 30-day
      mortality were 5.3% and 3.3%, respectively. Undergoing CN (hazard ratio [HR]
      0.48; 95% CI 0.44-0.52; p<0.0001) and treatment at academic centres (HR 0.88; 95%
      CI 0.81-0.95; p=0.001) were independently associated with improved OS. Limitation
      includes retrospective design with possible selection bias. CONCLUSIONS:
      Increased CN use continues in the modern era, with relatively low surgical
      morbidity. Further study is required to determine if the finding of lower all
      cause mortality in patients treated at academic centres is due to improved care
      or unmeasured confounders.

PMID- 28503233
TI  - Single penile incision for combined hypospadias and inguinal surgery: A
      comparative study.
AB  - INTRODUCTION: We sought to compare the surgical outcomes of hypospadias repair
      with correction of inguinal pathology using a single penile incision vs.
      conventional approach using two incisions. METHODS: This is a retrospective study
      that reviewed all patients who underwent concurrent surgical repair for both
      hypospadias and inguinal pathologies between January 2003 and November 2015.
      Patients were classified into Group A, conventional (inguinal or scrotal and
      penile incision) approach; or Group B, single penile incision approach. Baseline
      characteristics, including age, degree of hypospadias, type and laterality of
      inguinal pathology, operative time, and surgical outcomes, were collected.
      Between groups, variable comparisons were analyzed using Mann-Whitney U-Test and
      Fisher-exact test. Statistical significant set at <0.05. RESULTS: Seventy-six
      patients (Group A: 40; Group B: 36) were eligible for study. Baseline
      characteristics of both groups were comparable, with no significant statistical
      difference. Overall mean operative time for Group A was 139.3 +/- 56.2 minutes,
      while Group B was 107.8 +/- 46.7 minutes (Z=2.6; U=470.5; p=0.009). Two patients
      in Group A and two patients in Group B had testicular ascension, all of which
      also had hypospadias-related complications (p=1.0). Hypospadias-related
      complications in Group A included seven urethrocutaneous fistulae and two repair
      dehiscence. Eight urethrocutaneous fistulae, one urethral stricture, and two
      repair dehiscence occurred in Group B (p=0.448). Surgical outcome appearance in
      both groups were comparable, with no statistically significant difference
      (p=0.466). CONCLUSIONS: Single penile incision for both hypospadias repair and
      correction of inguinal pathology is a feasible technique and comparable to the
      conventional approach, with similar surgical outcomes and shorter overall
      operative time.

PMID- 28503234
TI  - Error reporting from the da Vinci surgical system in robotic surgery: A Canadian
      multispecialty experience at a single academic centre.
AB  - INTRODUCTION: The goal of the study is to evaluate and report on the third
      generation da Vinci surgical (Si) system malfunctions. METHODS: A total of 1228
      robotic surgeries were performed between January 2012 and December 2015 at our
      academic centre. All cases were performed by using a single, dual console, four
      arm, da Vinci Si robot system. The three specialties included urology,
      gynecology, and thoracic surgery. Studied outcomes included the robotic surgical
      error types, immediate consequences, and operative side effects. Error rate trend
      with time was also examined. RESULTS: Overall robotic malfunctions were
      documented on the da Vinci Si systems event log in 4.97% (61/1228) of the cases.
      The most common error was related to pressure sensors in the robotic arms
      indicating out of limit output. This recoverable fault was noted in 2.04%
      (25/1228) of cases. Other errors included unrecoverable electronic communication
      related in 1.06% (13/1228) of cases, failed encoder error in 0.57% (7/1228),
      illuminator-related in 0.33% (4/1228), faulty switch in 0.24% (3/1228), battery
      related failures in 0.24% (3/1228), and software/hardware error in 0.08% (1/1228)
      of cases. Surgical delay was reported only in one patient. No conversion to
      either open or laparoscopic occurred secondary to robotic malfunctions. In 2015,
      the incidence of robotic error rose to 1.71% (21/1228) from 0.81% (10/1228) in
      2014. CONCLUSIONS: Robotic malfunction is not infrequent in the current era of
      robotic surgery in various surgical subspecialties, but rarely consequential.
      Their seldom occurrence does not seem to affect patient safety or surgical
      outcome.

PMID- 28503235
TI  - Cautery artifact understages urothelial cancer at initial transurethral resection
      of large bladder tumours.
AB  - INTRODUCTION: We sought to determine how frequently cautery (thermal) artifact
      precludes an accurate determination of stage at initial transurethral resection
      of bladder tumour (TURBT) of large bladder tumours. METHODS: We queried our
      institution's billing data to identify patients who underwent TURBT for large
      bladder tumours >5cm (CPT 52240) by two urologists at an academic centre from
      January 2009 through April 2013. Only patients who underwent initial-staging
      TURBT for urothelial cancer were included. Pathological reports were reviewed for
      stage, number of separate pathological specimens per TURBT, and presence of
      cautery artifact. Operative reports were reviewed for whether additional cold cup
      biopsies were taken of other suspicious areas of the bladder, resident
      involvement, and type of electrocautery. RESULTS: We identified 119 patients who
      underwent initial staging TURBT for large tumours. Cautery artifact interfered
      with accurate staging in 7/119 (6%) of cases. Of these, six patients underwent
      restaging TURBT, with 50% percent experiencing upstaging to T2 disease. Tumour
      size, tumour grade, whether additional cold cup biopsies were taken, number of
      separate pathological specimens sent, and resident involvement were not
      associated with cautery artifact (all p>0.05). Bipolar resection had a higher
      rate of cautery artifact 5/42 (12%), compared to monopolar resection 2/77 (2.6%)
      approaching significance (p=0.095). CONCLUSIONS: Cautery artifact may delay
      accurate staging at initial TURBT for large tumours by understaging up to 6% of
      patients.

PMID- 28503236
TI  - Impact of neutrophil-to-lymphocyte ratio on effects of targeted therapy for
      metastatic renal cell carcinoma patients with extrapulmonary metastasis.
AB  - INTRODUCTION: The aim of our present study was to investigate the impact of the
      pretreatment neutrophil-to-lymphocyte ratio (NLR) on the antitumour effects of
      targeted agents in patients with metastatic renal cell carcinoma (mRCC). METHODS:
      The NLRs in 283 cases of molecular targeted therapy for mRCC were measured before
      starting the prescription of the molecular targeted agent. The significance of
      pretreatment NLR on the site of metastatic organs and on progression-free
      survival (PFS) in each case was analyzed. RESULTS: Metastases other than lung,
      which is defined as "extrapulmonary metastasis," were observed in 190 cases
      (67.1%). The median of pretreated NLR was 2.39 (0.49-68.7). In 97 of the 283
      cases, pretreated NLR was 3.0 or higher. These cases were categorized as the high
      NLR group and the rest as the low NLR group. When the cases with extrapulmonary
      metastasis were investigated and classified based on their pretreated NLR, 50%
      PFS in the high NLR and low NLR groups was 6.7 months and 12 months (p=0.0001),
      respectively. Multivariate analysis revealed that high NLR (>3.0) was an
      independent predictive factor for PFS in the cases with extrapulmonary metastasis
      (hazard ratio 2.762; p<0.0001), while there was no significant difference between
      PFS in the high and low NLR groups in cases with no extrapulmonary metastasis
      (p=0.3457). CONCLUSIONS: Our data indicate that the predictive significance of
      the NLR in mRCC cases involving targeted therapy depends on the metastatic
      organs. NLR is an independent predictive factor of PFS in cases of mRCC with
      extrapulmonary metastasis treated with targeted therapy.

PMID- 28503237
TI  - Modified C index: Novel predictor of postoperative renal functional loss of
      laparoscopic partial nephrectomy.
AB  - INTRODUCTION: We aimed to develop a scoring system to quantify the distance
      between the renal hilum and renal tumour, termed the modified C index (m-CI), and
      to predict renal functional loss (RFL) following laparoscopic partial nephrectomy
      (LPN). METHODS: The m-CI was measured by using computed tomography in 113
      patients who underwent LPN between May 2003 and June 2014. The RFL following LPN
      was calculated by examining the estimated glomerular filtration rate (eGFR) and
      radioisotope renography one year postoperatively. The Pythagorean theorem was
      used to calculate the distance from the tumour centre to the renal hilum. The
      distance was divided by the tumour radius to obtain the m-CI. The correlation
      between the m-CI and the postoperative RFL were evaluated using Pearson's
      coefficient values. Multivariate logistic regression models were used to assess
      the potential predictive factors of RFL following LPN. The correlation between
      the m-CI and the operative time, ischemia time, and blood loss during LPN were
      also evaluated by the unpaired t-test. RESULTS: Pearson's coefficient values
      between the postoperative RFL and the m-CI and C index were 0.294 and 0.173,
      respectively. In the multivariate analysis, the resected volume (p=0.031) and m
      CI (p=0.036) significantly correlated with the postoperative RFL following LPN.
      The operative time (p<0.001), ischemia time (p=0.028), and blood loss (p=0.047)
      during LPN was significantly longer and larger, respectively, in the group with
      shorter m-CI (<=4.5) than in the group with the longer m-CI (>4.5). CONCLUSIONS:
      The present study demonstrates that the m-CI can predict RFL following LPN, as
      well as the surgical difficulty.

PMID- 28503238
TI  - Epidemiology of prostate and kidney cancer in the Aboriginal population of
      Canada: A systematic review.
AB  - INTRODUCTION: Prostate and kidney cancer rates in the Aboriginal population of
      Canada is a growing issue. METHODS: A systematic review of prostate and kidney
      cancer epidemiology in the Aboriginal population of Canada was performed with
      international comparison and evaluation of present epidemiological disparities.
      PubMed, Medline, and Embase (from January 1946 to June 2016), relevant government
      published reports, and the websites of organizations contributing to prostate or
      kidney cancer guidelines were searched. We included studies that informed any of
      the three epidemiological questions this review is focused on answering. RESULTS:
      Two systematic reviews, two meta-analyses, five literature reviews, and 21 single
      study papers were included. The incidence and mortality rates of kidney cancer
      were elevated among Canadian Aboriginals when compared to the provincial or
      national population and to several international regions. No studies reported
      data on survival. Prostate cancer incidence, mortality, and survival rates were
      lower in Aboriginals provincially, nationally, and internationally, with
      incidence and survival reaching statistical significance. Elevated rate of risk
      factors for kidney cancer was a significant finding among Canadian Aboriginals.
      Aboriginals were screened for prostate cancer less than the general Canadian
      population, a trend also observed in the U.S. CONCLUSIONS: The elevated incidence
      and mortality of kidney cancer among Canadian Aboriginals is most likely
      attributable to the rise in lifestyle-based risk factors. Two correlations
      concerning prostate cancer are made. However, due to temporal and regional
      disparities in data, further investigation is required to elucidate these
      observations.

PMID- 28503229
TI  - CUA guideline on adult overactive bladder.

PMID- 28503239
TI  - A case of renal cell carcinoma in a patient with situs inversus: Operative
      considerations and a review of the literature.
AB  - Situs inversus, an uncommon mirror-image reversal of the major visceral and
      thoracic organs, is seldom of medical significance. However, the recognition of
      their unique anatomy is extremely important for those requiring surgical
      intervention. There are very few reported cases of renal cell carcinoma (RCC)
      developing in people with situs inversus. To our knowledge, this is the first
      reported case in Canada. A review of the literature only identified nine
      published cases worldwide. Here, we review and summarize pertinent information,
      including patient age and sex, size and location of tumour, method of surgery,
      and pathology. Our case, a 65-year-old male, presented with left flank pain and
      gross hematuria. He was diagnosed with left renal cancer as well as tumour
      thrombus extending into the left renal veins and inferior vena cava (IVC),
      clinical T3aN0M0. An abdomen and pelvis computed tomography (CT) scan showed a
      left-to-right reversal of his organs, a mirror-image, and situs inversus was
      diagnosed. A left radical nephrectomy with left renal vein and IVC tumour
      thrombectomy through a left open midline incision was performed.

PMID- 28503240
TI  - Response of renal cell carcinoma to ibrutinib, a bruton tyrosine kinase
      inhibitor, in a patient treated for chronic lymphocytic leukemia.

PMID- 28503241
TI  - Recurrent, bilateral, and metastatic pheochromocytoma in a young patient with
      Beckwith-Wiedemann syndrome: A genetic link?

PMID- 28503243
TI  - Appendix: Executive summary of CUA guideline on adult overactive bladder.

PMID- 28503242
TI  - Surgical excision of perineal nodular induration: A cyclist's third testicle.
AB  - Perineal nodular induration (PNI), or biker's nodule, is a rare, bothersome,
      pseudotumour. Herein, we describe the surgical technique used to treat a healthy
      cyclist who developed an enlarging PNI for five years that grew into a perineal
      mass. The mass prevented him from cycling due to worsening discomfort and
      heaviness. The PNI-associated mass was successfully removed by wide surgical
      excision and a local advancement flap. Subsequently, the patient resumed cycling.
      Histopathology report demonstrated a benign lesion with abundant ropy collagen
      with native smooth muscle, vessels, and rare fibroblast-like spindle cells. With
      the increasing popularity of cycling, PNI may become more common, and health
      providers should be aware of this rare entity and how it can be safely removed.

PMID- 28503245
TI  - Maximizing particle concentration in deterministic lateral displacement arrays.
AB  - We present an improvement to deterministic lateral displacement arrays, which
      allows higher particle concentration enhancement. We correct and extend previous
      equations to a mirror-symmetric boundary. This approach allows particles to be
      concentrated into a central channel, no wider than the surrounding gaps, thereby
      maximizing the particle enrichment. The resulting flow patterns were, for the
      first time, experimentally measured. The performance of the device with hard
      micro-spheres and cells was investigated. The observed flow patterns show
      important differences from our model and from an ideal pattern. The 18 MUm gap
      device showed 11-fold enrichment of 7 MUm particles and nearly perfect enrichment
      of more than 50-fold-for 10 MUm particles and Jurkat cells. This work shows a
      clear path to achieve higher-than-ever particle concentration enhancement in a
      deterministic microfluidic separation system.

PMID- 28503244
TI  - The Intergenerational Circumstances of Household Food Insecurity and Adversity.
AB  - Household food insecurity is linked with exposure to violence and adversity
      throughout the life course, suggesting its transfer across generations. Using
      grounded theory, we analyzed semistructured interviews with 31 mothers reporting
      household food insecurity where participants described major life events and
      social relationships. Through the lens of multigenerational interactions, 4
      themes emerged: (1) hunger and violence across the generations, (2) disclosure to
      family and friends, (3) depression and problems with emotional management, and
      (4) breaking out of intergenerational patterns. After describing these themes and
      how they relate to reports of food insecurity, we identify opportunities for
      social services and policy intervention.

PMID- 28503246
TI  - Particle concentrating and sorting under a rotating electric field by direct
      optical-liquid heating in a microfluidics chip.
AB  - We demonstrate a functional rotating electrothermal technique for rapidly
      concentrating and sorting a large number of particles on a microchip by the
      combination of particle dielectrophoresis (DEP) and inward rotating
      electrothermal (RET) flows. Different kinds of particles can be attracted
      (positive DEP) to or repelled (negative DEP) from electrode edges, and then the n
      DEP responsive particles are further concentrated in the heated region by RET
      flows. The RET flows arise from the spatial inhomogeneous electric properties of
      fluid caused by direct infrared laser (1470 nm) heating of solution in a rotating
      electric field. The direction of the RET flows is radially inward to the heated
      region with a co-field (the same as the rotating electric field) rotation.
      Moreover, the velocity of the RET flows is proportional to the laser power and
      the square of the electric field strength. The RET flows are significant over a
      frequency range from 200 kHz to 5 MHz. The RET flows are generated by the
      simultaneous application of the infrared laser and the rotating electric field.
      Therefore, the location of particle concentrating can be controlled within the
      rotating electric field depending on the position of the laser spot. This multi
      field technique can be operated in salt solutions and at higher frequency without
      external flow pressure, and thus it can avoid electrokinetic phenomena at low
      frequency to improve the manipulation accuracy for lab-on-chip applications.

PMID- 28503247
TI  - Reconfigurable microfluidic device with discretized sidewall.
AB  - Various microfluidic features, such as traps, have been used to manipulate flows,
      cells, and other particles within microfluidic systems. However, these features
      often become undesirable in subsequent steps requiring different fluidic
      configurations. To meet the changing needs of various microfluidic
      configurations, we developed a reconfigurable microfluidic channel with movable
      sidewalls using mechanically discretized sidewalls of laterally aligned
      rectangular pins. The user can deform the channel sidewall at any time after
      fabrication by sliding the pins. We confirmed that the flow resistance of the
      straight microchannel could be reversibly adjusted in the range of 101-105 Pa
      s/MUl by manually displacing one of the pins comprising the microchannel
      sidewall. The reconfigurable microchannel also made it possible to manipulate
      flows and cells by creating a segmented patterned culture of COS-7 cells and a
      coculture of human umbilical vein endothelial cells (HUVECs) and human lung
      fibroblasts (hLFs) inside the microchannel. The reconfigurable microfluidic
      device successfully maintained a culture of COS-7 cells in a log phase throughout
      the entire period of 216 h. Furthermore, we performed a migration assay of
      cocultured HUVEC and hLF spheroids within one microchannel and observed their
      migration toward each other.

PMID- 28503248
TI  - Stable microfluidic flow focusing using hydrostatics.
AB  - We present a simple technique to generate stable hydrodynamically focused flows
      by driving the flow with hydrostatic pressure from liquid columns connected to
      the inlets of a microfluidic device. Importantly, we compare the focused flows
      generated by hydrostatic pressure and classical syringe pump driven flows and
      find that the stability of the hydrostatic pressure driven technique is
      significantly better than the stability achieved via syringe pumps, providing
      fluctuation-free focused flows that are suitable for sensitive microfluidic flow
      cytometry applications. We show that the degree of flow focusing with the
      hydrostatic method can be accurately controlled by the simple tuning of the
      liquid column heights. We anticipate that this approach to stable flow focusing
      will find many applications in microfluidic cytometry technologies.

PMID- 28503249
TI  - Hierarchical Models for Multiple, Rare Outcomes Using Massive Observational
      Healthcare Databases.
AB  - Clinical trials often lack power to identify rare adverse drug events (ADEs) and
      therefore cannot address the threat rare ADEs pose, motivating the need for new
      ADE detection techniques. Emerging national patient claims and electronic health
      record databases have inspired post-approval early detection methods like the
      Bayesian self-controlled case series (BSCCS) regression model. Existing BSCCS
      models do not account for multiple outcomes, where pathology may be shared across
      different ADEs. We integrate a pathology hierarchy into the BSCCS model by
      developing a novel informative hierarchical prior linking outcome-specific
      effects. Considering shared pathology drastically increases the dimensionality of
      the already massive models in this field. We develop an efficient method for
      coping with the dimensionality expansion by reducing the hierarchical model to a
      form amenable to existing tools. Through a synthetic study we demonstrate
      decreased bias in risk estimates for drugs when using conditions with different
      true risk and unequal prevalence. We also examine observational data from the
      MarketScan Lab Results dataset, exposing the bias that results from aggregating
      outcomes, as previously employed to estimate risk trends of warfarin and
      dabigatran for intracranial hemorrhage and gastrointestinal bleeding. We further
      investigate the limits of our approach by using extremely rare conditions. This
      research demonstrates that analyzing multiple outcomes simultaneously is feasible
      at scale and beneficial.

PMID- 28503251
TI  - On convex least squares estimation when the truth is linear.
AB  - We prove that the convex least squares estimator (LSE) attains a n-1/2 pointwise
      rate of convergence in any region where the truth is linear. In addition, the
      asymptotic distribution can be characterized by a modified invelope process.
      Analogous results hold when one uses the derivative of the convex LSE to perform
      derivative estimation. These asymptotic results facilitate a new consistent
      testing procedure on the linearity against a convex alternative. Moreover, we
      show that the convex LSE adapts to the optimal rate at the boundary points of the
      region where the truth is linear, up to a log-log factor. These conclusions are
      valid in the context of both density estimation and regression function
      estimation.

PMID- 28503250
TI  - Localizing Sources of Brain Disease Progression with Network Diffusion Model.
AB  - Pinpointing the sources of dementia is crucial to the effective treatment of
      neurodegenerative diseases. In this paper, we propose a diffusion model with
      impulsive sources over the brain connectivity network to model the progression of
      brain atrophy. To reliably estimate the atrophy sources, we impose sparse
      regularization on the source distribution and solve the inverse problem with an
      efficient gradient descent method. We localize the possible origins of
      Alzheimer's disease (AD) based on a large set of repeated magnetic resonance
      imaging (MRI) scans in Alzheimer's Disease Neuroimaging Initiative (ADNI)
      database. The distribution of the sources averaged over the sample population is
      evaluated. We find that the dementia sources have different concentrations in the
      brain lobes for AD patients and mild cognitive impairment (MCI) subjects,
      indicating possible switch of the dementia driving mechanism. Moreover, we
      demonstrate that we can effectively predict changes of brain atrophy patterns
      with the proposed model. Our work could help understand the dynamics and origin
      of dementia, as well as monitor the progression of the diseases in an early
      stage.

PMID- 28503252
TI  - New Insights into Sequential Infiltration Synthesis.
AB  - Sequential infiltration synthesis (SIS) is a process derived from ALD in which a
      polymer is infused with inorganic material using sequential, self-limiting
      exposures to gaseous precursors. SIS can be used in lithography to harden polymer
      resists rendering them more robust towards subsequent etching, and this permits
      deeper and higher-resolution patterning of substrates such as silicon. Herein we
      describe recent investigations of a model system: Al2O3 SIS using trimethyl
      aluminum (TMA) and H2O within the diblock copolymer, poly(styrene-block-methyl
      methacrylate) (PS-b-PMMA). Combining in-situ Fourier transform infrared
      absorption spectroscopy, quartz-crystal microbalance, and synchrotron grazing
      incidence small angle X-ray scattering with high resolution scanning transmission
      electron microscope tomography, we elucidate important details of the SIS
      process: 1) TMA adsorption in PMMA occurs through a weakly-bound intermediate; 2)
      the SIS kinetics are diffusion-limited, with desorption 10* slower than
      adsorption; 3) dynamic structural changes occur during the individual precursor
      exposures. These findings have important implications for applications such as
      SIS lithography.

PMID- 28503253
TI  - Research Progress on Signaling Pathway-Associated Oxidative Stress in Endothelial
      Cells.
AB  - Studying the mechanisms of oxidative stress in endothelial cells is vital to the
      discovery of novel drugs for the treatment of cardiovascular disease. This
      article reviews the progress within the field of the role of oxidative responses
      in the physiology and growth of endothelial cells and emphasizes the effects of
      several main signal pathways involved in the oxidative stress of endothelial
      cells. Herein, we aim to provide scientific direction that can serve as a basis
      for researchers specializing in the signaling pathway of oxidative stress.

PMID- 28503255
TI  - The Biochemical Cascades of the Human Pancreatic beta-Cells: The Role of
      MicroRNAs.
AB  - Diabetes mellitus is a disease that poses a burden to the health care system due
      to its prevalence and chronic nature. Understanding beta cell pathophysiology may
      lead to future therapeutic options for diabetes mellitus type 1 and 2. MicroRNAs
      (MiR) fine-tune beta cell biochemical cascades through specific protein targets.
      This review argues that miRs may play a critical role in human islet beta cell
      biology and are potential candidates for a new pharmacological strategy. We have
      reviewed and presented how miRs fine tune four biochemical cascades in islet beta
      cells: glucose stimulated insulin secretion, beta cell replication, apoptosis,
      and development. Only studies that examine human pancreatic islets either in
      vitro or in vivo are included. The unveiling role of miR pathways in regulating
      human islet beta cell biology could open the door for diagnostic and therapeutic
      methods for diabetes mellitus prevention and therapy.

PMID- 28503254
TI  - Management of Potential Long-Term Toxicities in Breast Cancer Patients.
AB  - Breast cancer is the most common non-cutaneous malignancy among women, and there
      are over 3 million breast cancer survivors living in the United States today.
      Excellent cure rates with modern therapies are associated with substantial
      toxicities for many women; it is important that health care providers attend to
      the resulting symptoms and issues to optimize quality of life in this population.
      In this article, we review management options for potential long term toxicities
      in breast cancer survivors, with a particular focus on bone health, fertility
      preservation, premature menopause, cardiac dysfunction, and cognitive impairment.

PMID- 28503256
TI  - Socialization of Culture and Coping with Discrimination Among American Indian
      Families: Examining Cultural Correlates of Youth Outcomes.
AB  - OBJECTIVE: The current study examines the interrelations between observed
      parental cultural socialization and socialization of coping with discrimination,
      and youth outcomes among a sample of 92 American Indian adolescents and their
      parents in a rural reservation. METHOD: Path analysis is used to examine the
      relationships among observed parental socialization (cultural socialization and
      socialization of coping with discrimination), and youth-reported perceived
      discrimination, ethnic identity and depression. RESULTS: Findings reveal that
      higher levels of observed parental cultural socialization and socialization of
      coping with discrimination predict lower levels of depression as reported by
      youth 1 year later. Path analyses also show that observed parental cultural
      socialization and socialization of coping with discrimination are positively
      associated with youth ethnic identity. CONCLUSIONS: These findings point to the
      importance of integrating familial socialization of culture and coping with
      discrimination in fostering resilience among American Indian youth.

PMID- 28503257
TI  - Trends with neoadjuvant radiotherapy and clinical staging for those with rectal
      malignancies.
AB  - AIM: To see how patterns of care changed over time, and how institution type
      effected these decisions. METHODS: A retrospective analysis was performed using
      the National Cancer Database, looking at all patients that were diagnosed with
      rectal cancer from 1998 to 2011. We tested differences in rates of treatment and
      stage migration using chi2 tests and logistic regression models. RESULTS: A
      review of ninety thousand five hundred and ninety four subjects underwent
      multimodality therapy for cancer of the rectum. Staging and response to treatment
      varied greatly between centers. Forty-six percent of the time staging was missing
      in academic practices, vs fifty-four percent of the time in community centers (P
      < 0.001). As a result, twenty-percent were down-staged and eight percent up
      staged in academia, whereas only fifteen percent were down-staged and 8% up
      staged in community practices (P < 0.001). Forty-two percent of individuals
      underwent radiation before surgery in 1998. Within two years this increased to
      fifty-three percent. This increased to eighty-six percent by 2011 (P < 0.001).
      Institution specific treatment varied greatly. Fifty-one percent received therapy
      before surgery in academic centers in 1998. Thirty-nine percent followed this
      pattern in the same year in the community (P < 0.001). By 2011, ninety-one
      percent received radiation before their procedure in academic centers, vs eighty
      four percent in the community (P < 0.001). Rates of adoption were better in
      academia, although an increase was seen in both center types. CONCLUSION: From
      the study dates of 1998 to 2011, preoperative treatment with radiation has been
      on the rise. There is certainly an increased rate of use of radiation in
      academia, however, this trend is also seen in the community. Practice patterns
      have evolved over time, although rates of assigning clinical stage are grossly
      underreported prior to initiation of preoperative therapy.

PMID- 28503258
TI  - Feasibility of pancreatectomy following high-dose proton therapy for unresectable
      pancreatic cancer.
AB  - AIM: To review surgical outcomes for patients undergoing pancreatectomy after
      proton therapy with concomitant capecitabine for initially unresectable
      pancreatic adenocarcinoma. METHODS: From April 2010 to September 2013, 15
      patients with initially unresectable pancreatic cancer were treated with proton
      therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients
      received 59.40 Gy (RBE) to the gross disease and 1 patient received 50.40 Gy
      (RBE) to high-risk nodal targets. There were no treatment interruptions and no
      chemotherapy dose reductions. Six patients achieved a radiographic response
      sufficient to justify surgical exploration, of whom 1 was identified as having
      intraperitoneal dissemination at the time of surgery and the planned
      pancreatectomy was aborted. Five patients underwent resection. Procedures
      included: Laparoscopic standard pancreaticoduodenectomy (n = 3), open pyloris
      sparing pancreaticoduodenectomy (n = 1), and open distal pancreatectomy with
      irreversible electroporation (IRE) of a pancreatic head mass (n = 1). RESULTS:
      The median patient age was 60 years (range, 51-67). The median duration of
      surgery was 419 min (range, 290-484), with a median estimated blood loss of 850
      cm3 (range, 300-2000), median ICU stay of 1 d (range, 0-2), and median hospital
      stay of 10 d (range, 5-14). Three patients were re-admitted to a hospital within
      30 d after discharge for wound infection (n = 1), delayed gastric emptying (n =
      1), and ischemic gastritis (n = 1). Two patients underwent R0 resections and
      demonstrated minimal residual disease in the final pathology specimen. One
      patient, after negative pancreatic head biopsies, underwent IRE followed by
      distal pancreatectomy with no tumor seen in the specimen. Two patients underwent
      R2 resections. Only 1 patient demonstrated ultimate local progression at the
      primary site. Median survival for the 5 resected patients was 24 mo (range, 10
      30). CONCLUSION: Pancreatic resection for patients with initially unresectable
      cancers is feasible after high-dose [59.4 Gy (RBE)] proton radiotherapy with a
      high rate of local control, acceptable surgical morbidity, and a median survival
      of 24 mo.

PMID- 28503259
TI  - Five-year outcomes of laparoscopic sleeve gastrectomy as a primary procedure for
      morbid obesity: A prospective study.
AB  - AIM: To prospectively evaluate the postoperative morbi-mortality and weight loss
      evolution of patients who underwent a laparoscopic sleeve gastrectomy (LSG) as a
      primary bariatric procedure during 5 years of follow-up. METHODS: Since 2006,
      data from patients undergoing a highly restrictive primary LSG have been
      prospectively registered in a database and analysed. Preoperative co-morbid
      conditions, operating time, hospital stay, early and late complications rate and
      evolution of weight loss after 5 years of follow-up were analysed. RESULTS: A
      total of 156 patients were included, 74.3% of whom were women. The mean age was
      43.2 +/- 13.1 years and the mean body mass index (BMI) was 41.5 +/- 7.9 kg/m2.
      Seventy patients (44.8%) presented a BMI under 40 kg/m2. The mortality rate was
      0%. The leakage rate was 1.2%, and the total 30-d morbidity rate was 5.1%
      (8/156). With a mean follow-up of 32.7 +/- 28.5 (range 6-112) mo, the mean
      percent of excess of weight loss (%EWL) was 82.0 +/- 18.8 at 1 year, 76.7 +/-
      21.3 at 3 years and 60.3 +/- 28.9 at 5 years. The mean percent of excess of BMI
      loss (%EBMIL) was 94.9 +/- 22.4 at 1 year, 89.4 +/- 27.4 at 3 years and 74.8 +/-
      29.4 at 5 years. Patients with preoperative BMI less than 40 kg/m2 achieved
      greater weight loss than did the overall study population. Diabetes remitted in
      75% of the patients and HTA improved in 71.7%. CPAP masks were withdrawn in all
      patients with obstructive sleep apnoea. CONCLUSION: LSG built with a narrow 34 F
      bougie and starting 3 cm from the pylorus proved to be safe and highly effective
      in terms of weight loss as a stand-alone procedure, particularly in patients with
      a preoperative BMI lower than 40 kg/m2.

PMID- 28503260
TI  - Dynamics of Hexavalent Chromium in Four Types of Aquaculture Ponds and Its
      Effects on the Morphology and Behavior of Cultured Clarias gariepinus (Burchell
      1822).
AB  - Hexavalent chromium is a bio accumulative toxic metal in water and fish. It
      enters aquaculture ponds mainly through anthropogenic sources. Hexavalent
      chromium concentrations and its effects on the morphology and behavior of Clarias
      gariepinus were investigated from four aquaculture ponds for 12 weeks. Chromium
      was measured using diphenyl carbohdrazide method; alkalinity and hardness were
      measured using colometric method and analyzed with Bench Photometer. Temperature
      and pH were measured using pH/EC/TDS/Temp combined tester. Temporal and spatial
      replications of samples were done with triplicates morphological and behavioural
      effects of the metal on fish were observed visually. Chromium ranged from no
      detection to 0.05 mg/L, alkalinity 105 to 245 mg/L, hardness 80 to 165 mg/L, pH
      6.35 to 8.03 and temperature 29.1 to 35.9 degrees C. Trend in the chromium
      concentrations in the ponds is natural > earthen > concrete > collapsible. There
      was a significant difference (P < 0.05) in chromium, alkalinity, water hardness,
      pH and temperature among the four ponds. Significant positive correlation also
      existed between alkalinity, water hardness, pH, with chromium. Morphological and
      behavioural changes observed in the fish include irregular swimming, frequent
      coming to the surface, dark body colouration, mucous secretion on the body,
      erosion of gill epithelium, fin disintegration, abdominal distension and
      lethargy. High chromium concentration in natural pond was due to anthropogenic
      run-off of materials in to the pond. Acidic pH, low alkalinity, low water
      hardness also contributed to the high chromium concentration. Morphological and
      behavioural changes observed were attributed to the high concentrations, toxicity
      and bio accumulative effect of the metal. Toxicity of chromium to fish in
      aquaculture could threaten food security. Watershed best management practices and
      remediation could be adopted to reduce the effects of toxicity of chromium on
      pond water quality, fish flesh quality and fish welfare.

PMID- 28503261
TI  - Anti-Photoaging Effects of Angelica acutiloba Root Ethanol Extract in Human
      Dermal Fibroblasts.
AB  - The effects that ultraviolet rays elicit on collagen synthesis and degradation
      are the most common causes of wrinkle formation and photo-aging in skin. The
      objectives of this study were to evaluate the effects of Angelica acutiloba root
      ethanol extract (AAEE) to promote collagen synthesis and inhibit collagen
      degradation in human dermal fibroblasts. By examining total polyphenol and
      flavonoid contents, electron donating ability, radical scavenging activity, and
      superoxide dismutase-like activity, we found that AAEE exhibited fairly good
      antioxidant activity. Treatment with AAEE significantly increased type I
      procollagen production by cultured fibroblasts, as well as reduced ultraviolet
      induced matrix metalloproteinase-1 (MMP-1) expression and MMP-2 activity in a
      dose-dependent manner (p < 0.05). In addition, AAEE significantly increased TIMP
      1 mRNA expression (p < 0.05), although without an associated dose-dependent
      increase in TIMP-1 protein expression. In summary, we suggest that AAEE may be a
      potentially effective agent for the prevention or alleviation of skin-wrinkle
      formation induced by ultraviolet rays.

PMID- 28503262
TI  - Detection of Toxic Heavy Metal, Co(II) Trace via Voltammetry with Semiconductor
      Microelectrodes.
AB  - The cobalt (Co(II)) ion is a main component of alloys and considered to be
      carcinogenic, especially due to the carcinogenic and toxicological effects in the
      aquatic environment. The toxic trace of the Co(II) detection was conducted using
      the infrared photodiode electrode (IPDE) using a working electrode, via the
      cyclic and square-wave anodic stripping voltammetry. The results indicated a
      sensitive oxidation peak current of Co(II) on the IPDE. Under the optimal
      conditions, the common-type glassy carbon, the metal platinum, the carbon paste,
      and the carbon fiber microelectrode were compared with the IPDE in the
      electrolyte using the standard Co(II). The IPDE was found to be far superior to
      the others.

PMID- 28503263
TI  - Spontaneous Peripheral Ameloblastic Odontoma in a Male Sprague-Dawley Rat.
AB  - Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring
      in the extraosseous region. The present report describes a spontaneous tumor in
      male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right
      mandibular region was first observed when the rat was 42 weeks and remained until
      the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a
      well demarcated nodule, approximately 2.5 * 2.0 * 2.0 cm, protruded from the
      ventral area of the right mandible. The nodule was not attached to mandibular
      bone and was not continuous with the normal teeth. Histopathologically, the tumor
      was characterized by the simultaneous occurrence of an ameloblastomatous
      component and composite odontoma-like elements within the same tumor. The
      epithelial portion formed islands or cords resembling the follicle or plexiform
      pattern typical of ameloblastoma and was surrounded by mesenchymal tissue.
      Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel)
      resembling odontoma was observed in the center of the tumor. Mitotic figures were
      rare, and areas of cystic degeneration were present. Immunohistochemically, the
      epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the
      mesenchymal component and odontoblast-like cells were positive for vimentin, in
      the same manner as in normal teeth. On the basis of these findings, the tumor was
      diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular
      region in a SD rat. In the present study, we report the uncommon spontaneous
      peripheral ameloblastic odontoma in the SD rat. We also discuss here the
      morphological characteristics, origin, histochemical, and immunohistochemical
      features for the diagnosis of this tumor.

PMID- 28503264
TI  - Skin Wound Healing Effects and Action Mechanism of Acai Berry Water Extracts.
AB  - The purpose of this study was to investigate the wound healing effect of acai
      berry water extracts (ABWE) and a possible underlying mechanism involved in its
      action using various in vitro and in vivo models. The wound healing effect of
      ABWE was evaluated by migration assay using HS68 fibroblast cells. In addition,
      its effect on mRNA expression of procollagen, fibronectin, and MMP-1 was
      determined. Moreover, the wound healing effect of ABWE was evaluated in in vivo
      wound models through macroscopic and microscopic observation. In addition, mRNA
      expression levels of wound related genes were determined. Results revealed that
      ABWE was not cytotoxic. It increased migration of HS68 fibroblast cells. ABWE
      increased mRNA expression levels of fibronectin but decreased the mRNA expression
      levels of MMP-1. ABWE also showed significantly potent wound healing effect in
      vivo based on macroscopic and histopathological observation and mRNA expression
      evaluation for wound related genes. Taken together, our results indicated that
      ABWE might have potential as a wound healing agent.

PMID- 28503265
TI  - The Effects of Caffeine on the Long Bones and Testes in Immature and Young Adult
      Rats.
AB  - This study was to evaluate the age-dependent effects of caffeine exposure on the
      long bones and reproductive organs using male rats. A total of 15 immature male
      rats and 15 young adult male rats were allocated randomly to three groups: a
      control group and two groups fed caffeine with 120 and 180 mg/kg/day for 4 weeks.
      Exposure to caffeine at either dose significantly reduced body weight gain; a
      proportional reduction in muscle and fat mass in immature animals, whereas a
      selective reduction in fat mass with relatively preserved muscle mass in young
      adult animals. The long bones of immature rats exposed to caffeine were
      significantly shorter and lighter than those of control animals along with
      decreased bone minerals. However, there was no difference in the length or weight
      of the long bones in young adult rats exposed to caffeine. Exposure to caffeine
      reduced the size and absolute weight of the testes significantly in immature
      animals in comparison to control animals, but not in young adult animals exposed
      to caffeine. In contrast, the adrenal glands were significantly heavier in
      caffeine-fed young adult rats in comparison to control animals, but not in
      caffeine-fed immature rats. Our results clearly show that the negative effects of
      caffeine on the long bones and testes in rats are different according to the age
      of the rat at the time of exposure, and might therefore be caused by changes to
      organ sensitivity and metabolic rate at different developmental stages. Although
      the long bones and testes are more susceptible to caffeine during puberty,
      caffeine has negative effects on body fat, bone minerals and the adrenal glands
      when exposure occurs during young adulthood. There is a need, therefore, to
      educate the public the potential dangers of caffeine consumption during puberty
      and young adulthood.

PMID- 28503267
TI  - Consultation - Not the time for shortcuts.

PMID- 28503266
TI  - Inhalation Toxicity of Bisphenol A and Its Effect on Estrous Cycle, Spatial
      Learning, and Memory in Rats upon Whole-Body Exposure.
AB  - Bisphenol A (BPA) is a monomer used in a polymerization reaction in the
      production of polycarbonate plastics. It has been used in many consumer products,
      including plastics, polyvinyl chloride, food packaging, dental sealants, and
      thermal receipts. However, there is little information available on the
      inhalation toxicity of BPA. Therefore, the aim of this study was to determine its
      inhalation toxicity and effects on the estrous cycle, spatial learning, and
      memory. Sprague-Dawley rats were exposed to 0, 10, 30, and 90 mg/m3 BPA, 6
      hr/day, 5 days/week for 8 weeks via whole-body inhalation. Mortality, clinical
      signs, body weight, hematology, serum chemistry, estrous cycle parameters,
      performance in the Morris water maze test, and organ weights, as well as gross
      and histopathological findings, were compared between the control and BPA
      exposure groups. Statistically significant changes were observed in serum
      chemistry and organ weights upon exposure to BPA. However, there was no BPA
      related toxic effect on the body weight, food consumption, hematology, serum
      chemistry, organ weights, estrous cycle, performance in the Morris water maze
      test, or gross or histopathological lesions in any male or female rats in the BPA
      exposure groups. In conclusion, the results of this study suggested that the no
      observable adverse effect level (NOAEL) for BPA in rats is above 90 mg/m3/6
      hr/day, 5 days/week upon 8-week exposure. Furthermore, BPA did not affect the
      estrous cycle, spatial learning, or memory in rats.

PMID- 28503268
TI  - The roles of men in family planning - a study of married men at the UKM primary
      care clinic.
AB  - INTRODUCTION: Traditionally, family planning initiatives were concentrated on
      women despite it being a family matter. As family dynamics evolved over the
      years, fathers' involvement in family planning has become crucial in enhancing
      the family well-being. OBJECTIVES: This study aimed to identify the role played
      by men in family planning activities and the association of socio-economic
      characteristics with these roles. METHODOLOGY: This was a cross-sectional study
      carried out in a university primary care clinic. All married male attendees to
      the clinic, aged 50 years and below, were approached to answer a set of self
      administered questionnaires, asking for their involvement in family planning
      practices. The data were analysed using descriptive and inferential statistics.
      RESULTS: There were 167 participants in the study. A high proportion of men
      participated in the discussions regarding previous pregnancies (60.42%), future
      child planning (89.76%) and desired family size (89.76%). However, the
      discussions on the usage of family planning methods (FPMs; 39.16%) were
      significantly low. Socio-economic factors associated with higher likelihood of
      men discussing family planning activities were older age (p < 0.0), higher
      education level (p = 0.010), higher monthly income (p < 0.001) and longer
      duration of marriage (p = 0.0049). CONCLUSIONS: The level of participation of men
      varied in the discussions of four family planning activities. The roles taken by
      men in family planning were associated with older age and higher socio-economic
      class. The majority of men needs to be encouraged to play a more active role in
      the discussion of FPMs.

PMID- 28503269
TI  - An assessment of patient waiting and consultation time in a primary healthcare
      clinic.
AB  - Waiting is a common phenomenon in the doctor's waiting room. The purpose of this
      audit is to assess patient waiting time and doctor consultation time in a primary
      healthcare clinic and to formulate strategies for improvement. This audit was
      conducted at a primary care clinic for 4 weeks using the universal sampling
      method. All patients who attended the clinic during this period was included in
      the study except for those who required more time to be seen such as those who
      were critically ill, aggressive or those who came for repeat medication or
      procedures only without needing to see the doctor. The time of arrival was
      captured using the queue management system (QMS) and then the patient was given a
      timing chit which had to be manually filled by the staff at every station. The
      waiting time for registration, pre-consultation, consultation, appointment,
      payment and pharmacy were recorded as well as consultation time. The data were
      entered into the statistical software SPSS version 17 for analysis. version 17.
      Results showed that more than half of the patients were registered within 15
      minutes (53%) and the average total waiting time from registration to seeing a
      doctor was 41 minutes. Ninety-nine percentage of patients waited less than 30
      minutes to get their medication. The average consultation time was 18.21 minutes.
      The problems identified in this audit were addressed and strategies formulated to
      improve the waiting and consultation time were carried out including increasing
      the number of staff at the registration counter, enforcing the staggered
      appointment system for follow-up patients and improving the queuing system for
      walk-in patients.

PMID- 28503270
TI  - Early management of head injury in adults in primary care.
AB  - Head injury is common and preventable. Assessment of the head injury patient
      includes airway, cervical spine protection, breathing, circulation, haemorrhage
      control and the Glasgow Coma Scale. Hypotension, hypoxia, hypocarbia and
      hypercarbia should be avoided by continuous monitoring of vital signs and hourly
      head chart to prevent secondary brain injury. This paper aims to assist primary
      healthcare providers to select the appropriate patient for transfer and imaging
      for further management of head injury.

PMID- 28503271
TI  - Pulled/nursemaid's elbow.
AB  - Nursemaid's elbow is a radial head subluxation caused by axial traction on the
      extended arm while the forearm is pronated, allowing for slippage of the radial
      head. A 2-year-old boy presented with pain, swelling and reduced range of
      movement of the right elbow for 4 days. The mother noted that the child was
      moving the right upper limb less often and there was tenderness over the right
      elbow. X-ray of the right elbow showed subluxation of the elbow joint with no
      obvious fracture. A trial of conservative management was decided upon and the
      patient was placed on a right elbow backslab with the right forearm in a supine
      position. On follow-up, there was no swelling, tenderness or neurological deficit
      noted. A repeate x-ray revealed normal findings.

PMID- 28503272
TI  - Von Hippel - Lindau disease.
AB  - Von Hippel-Lindau (VHL) disease is a rare autosomal dominantly inherited
      multisystem disorder characterised by the development of a variety of benign and
      malignant tumours. We report a case of VHL disease that was inherited by a
      daughter from her father, who both presented at a young age with progressive
      headache and were found to have a posterior fossa haemangioblastoma (HB) on
      magnetic resonance imaging (MRI). Multiple benign pancreatic and renal cysts were
      also noted in both patients.

PMID- 28503273
TI  - Bilateral optic neuritis with maculopathy: A rare manifestation of dengue fever.
AB  - Dengue fever is a common mosquito-borne disease, which is endemic in tropical and
      subtropical countries. Bilateral optic neuropathy is a relatively unusual dengue
      related ocular complication. Here, we present a case of bilateral optic neuritis
      with maculopathy complicating dengue infection.

PMID- 28503274
TI  - Is it as dangerous as it looks?
AB  - A common bony protrusion that occurs over the hard palate is sometimes mistaken
      for a malignancy especially when it is large. This bony growth is a torus
      palatinus (TP), which is a benign bony prominence over the hard palate. It occurs
      most commonly in bilateral multiple form, and is often located at the canine to
      premolar area. A basic knowledge of the assessment and management of TP is
      important, particularly for the first-line family physician to ensure that the
      correct information is given to the patient.

PMID- 28503275
TI  - An elderly man with an air-fluid level in the middle ear.
AB  - A 68-year-old Malay man who is a rubber tapper, presented with a large painful
      right-sided neck swelling for 6 months, which was gradually increasing in size
      and associated with odynophagia, dysphagia, hoarseness and significant weight
      loss. He did not complain of any ear symptoms, but on further questioning, he
      admitted having a 3-week history of occasional tinnitus and reduced hearing on
      the right ear. Other ear symptoms were negative.

PMID- 28503276
TI  - Do statins adversely affect the HbA1c of diabetic patients?
AB  - This paper discusses the adverse effect of statins on the HbA1c levels of
      diabetic patients. Studies have shown that statins may slightly worsen the HbA1c
      level. The effects vary depending on the type of statins, the dosage and the
      duration of therapy. However, it has been confirmed that statin use has benefits
      that outweigh its harms. Therefore, a diabetic patient should be given advice on
      the need for appropriate lifestyle changes and the importance of continuing the
      statins.

PMID- 28503277
TI  - Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance
      in patients with thalassemia major in Iran: A meta-analysis study.
AB  - BACKGROUND: This study aimed to investigate the prevalence of diabetes, impaired
      fasting glucose (IFG) and impaired glucose tolerance (IGT) in Iranian patients
      with thalassemia major. METHODS: The current study has been conducted based on
      PRISMA guideline. To obtain the documents, Persian and English scientific
      databases such as Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed,
      ScienceDirect, Cochrane, Web of Science, Springer, Wiley Online Library as well
      as Google Scholar were searched until December 2015. All steps of the study were
      conducted by two authors independently. To the high heterogeneity of the studies,
      the random effect model was used to combine studies. Data were analyzed using
      STATA Version 11.1 software. RESULTS: Thirty-two studies involving 3959 major
      thalassemia patients with mean age of 16.83 years were included in the meta
      analysis. The prevalence of diabetes in Iranian patients with thalassemia major
      was estimated as 9% (95% CI: 6.8-10.5) and estimated rate was 12.6% (95% CI: 6.1
      19.1) for males and 10.8% (95% CI: 8.2-14.5) for females. The prevalence of IFG
      and IGT were 12.9% (95% CI: 7-18.8) and 9.6% (95% CI: 6.6-12.5) respectively. No
      relationship between serum ferritin and development of diabetes was noted.
      CONCLUSION: The prevalence of diabetes, IFG, and IGT in patients with thalassemia
      major in Iran is high and accordingly requires new management strategies and
      policies to minimize endocrine disorders in Iranian patients with thalassemia
      major. Screening of patients for the early diagnosis of endocrine disorders
      particularly diabetes, IFG, and IGT is recommended.

PMID- 28503278
TI  - Conjugate and 23-valent pneumococcal polysaccharide booster vaccination in
      asplenic patients with thalassemia major: A randomized clinical trial study.
AB  - BACKGROUND: Pneumococcal vaccine provides protection against invasive
      pneumococcal disease in population at risk. This study was conducted to compare
      the antibody response to 13-valent pneumococcal conjugate vaccine and 23-valent
      pneumococcal polysaccharide vaccine in patients with thalassemia major. METHODS:
      A randomized cross-over clinical trial was performed on 50 asplenic patients with
      thalassemia major who referred to thalassemia center at Bouali Sina Hospital,
      Sari, Iran from 2013 to 2014. Patients were divided into two equal groups. The
      first group received 13-valent pneumococcal conjugate vaccine (PCV) injected into
      the deltoid muscle at first and received 23-valent polysaccharide vaccine (PPV)
      by the same way two months later. The second group received PPV vaccine at first
      and PCV13 two months later. Levels of serum antibody were checked and measured by
      enzyme-linked immunosorbent assay (ELISA) before vaccination, and then 8 weeks
      after the first injection and 2 months after the second injection in all
      patients. Each time 0.5-ml dose of the vaccine was injected. RESULTS: Of the 50
      patients, three cases were excluded due to lack of cooperation and avoidance of
      vaccination. From 47 patient participants, 28 (59.6%) were males and 19 (40.4%)
      were females with age ranged between 20 to 44 years (average age of 29.6+/-1.4
      years). Pneumococcal IgG levels in a group that used PCV before PPV (Group A)
      increased from 114.5+/-87.7 to 1049+/-720 U/ml (p=0.0001) and in another group
      that used PPV before PCV (Group B) increased from 115+/-182.2 to 1497.3+/-920.3
      U/ml (P=0.0001). CONCLUSION: It can be concluded that PCV vaccine before PPV can
      be more effective in asplenic thalassemia major patients as a booster dose.

PMID- 28503279
TI  - Incidence and risk factors for cytomegalovirus in kidney transplant patients in
      Babol, northern Iran.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of death and
      possibly transplant rejection in kidney transplant (KT) patients. This study was
      conducted to investigate the incidence and risk factors of CMV disease in kidney
      transplant patients. METHODS: All end-stage renal disease (ESRD) patients who
      underwent kidney transplantation during 1998-2014 and their donors were assessed.
      All samples were followed-up for approximately 70 months. CMV was identified by
      polymerase chain reaction (PCR) and/or PP65 antigen in peripheral blood
      leukocytes along with clinical manifestations. RESULTS: A total of 1450 cases
      participated in the current study. CMV was diagnosed in 178 out of 725 (24.6%)
      kidney recipients. The annual incidence of CMV disease was 4.2%. Patients older
      than 40 years had a higher incidence of CMV disease. The level of CMV disease
      incidence in the 41-60 age group was 4 fold compared to those under 20 of age
      group (P=0.001). CONCLUSION: This study demonstrated that the incidence of CMV
      disease in our region is relatively low and also age more than 40 years and EBV
      infection are the important risk factors in kidney transplant patients. So care
      and monitoring of these patients are crucial in the first 5 months.

PMID- 28503280
TI  - Etiological approach of chylothorax in Babol, northern Iran.
AB  - BACKGROUND: Chylothorax results from leakage of lymph in the pleural cavity
      because of thoracic duct injury which is associated with severe metabolic
      disorders. The aim of this study was to evaluate the rate of chylothorax and its
      causes among hospitalized patients in Shahid Beheshti Hospital of Babol city,
      North of Iran. METHODS: In this cross-sectional study, all patients with
      chylothorax admitted to the surgery department of Shahid Beheshti Hospital during
      2002-2015 were included. Information including gender, age, duration of symptoms,
      laboratory findings, causes of disease and the type of treatment were extracted
      from the patients' records. RESULTS: Of the 42 patients, 27 (64.3%) were men and
      15 (35.7%) were women. The mean age of the study population was 51.03+/-16.95.
      The most common clinical symptoms were dyspnea (66.7%) and dyspnea with cough
      (21.4%), respectively. In all patients, the pleural fluid triglyceride level was
      greater than 110 mg/dl, whereas the presence of lymphatic in pleural fluid was
      eventful in 18 (42.8%) patients. The causes of the disease were traumatic
      (54.8%), non-traumatic (38.1%) and unknown (7.1%), which were not significantly
      correlated with gender. Nineteen (45.2%) patients were operated, 16 (38.1%)
      patients received supportive therapy, and 7 (16.7%) patients had the treatment of
      the underlying conditions and then supportive therapy. CONCLUSION: According to
      the results, trauma was the most common cause of chylothorax. Therefore,
      identification and control of the traumatic factors seem to be the steps to
      prevent and reduce the chylothorax incidence and its complications.

PMID- 28503281
TI  - Effect of SeptimebTM as a new natural extract on severe sepsis: A randomized
      clinical trial.
AB  - BACKGROUND: Septimeb as a herbal medicine has regulatory effects on inflammation.
      This study set to evaluate the effects of Septimeb among patients with sepsis on
      inflammatory biomarkers and survival rate. METHODS: In this randomized clinical
      trial, 51 patients with sepsis from the ICU and medical ward of Imam Khomeini
      Hospital were divided into two groups: Septimeb (n=25) and control group (n=26).
      In the control group, the patients received a standard treatment only for 7 days,
      while Septimeb group received Septimeb (6cc vial with 500cc serum glucose
      infusion 5% daily for one to two hours) plus standard treatment of sepsis for 7
      days. Then, blood samples were analyzed. APACHE (Acute Physiologic and Chronic
      Health Evaluation), SOFA (Sequential Organ Failure Assessment), and GCS (Glasgow
      Coma Score) values were calculated daily. RESULTS: Treatment with Septimeb showed
      a significant decrease in SOFA value (1.54+/-0.83) compared to the control group
      (2.39+/-0.88) (P<0.001) and a significant increase in GCS value (14.46+/-0.88)
      compared to the control group (12.86+/-1.78) (P<0.001). Improvements of these
      values can confirm the potential of Septimeb in the reduction of severity of
      sepsis (P<0.05). There were significant decreases in lactate and blood sugar and
      WBC levels. In addition, inflammatory factors such as ESR (Septimeb group:
      52.07+/-34.80, control group: 51.75+/-42.10, P=0.98) and CRP (Septimeb group:
      48.86+/-23.21, control group: 49.93+/-36.22, P=0.92) decreased, but did not show
      a significant reduction. CONCLUSION: Septimeb has positive effects on reduction
      of the severity of sepsis which leads to reduction of patients' mortality rates.

PMID- 28503282
TI  - Skeletal complications of brucellosis: A study of 464 cases in Babol, Iran.
AB  - BACKGROUND: Skeletal complication of brucellosis is common in endemic region of
      brucellosis, but its frequency has not been clearly determined. The aim of this
      study was to determine the frequency of skeletal complication in brucellosis
      patients in Babol, north of Iran. METHODS: From 2005-2015, 1252 cases of
      brucellosis were diagnosed at the Department of Infectious Diseases, Ayatollah
      Rouhani Teaching Hospital, in Babol, North of Iran. The diagnosis of brucellosis
      was established using serum agglutination test (SAT>=1/160), and 2
      mercaptoethanol (2ME>= 1/80) with clinical and epidemiological findings
      compatible with brucellosis. Among them, 464 (37.1%) cases demonstrated skeletal
      complication. The diagnosis of skeletal involvement was established with
      appropriate diagnostic facilities. The data were collected and analyzed. RESULTS:
      The mean age of these patients (299 males, 165 females) was 33.2+/-17.6 years.
      Three hundred-thirty four (72%) cases were from rural areas. In 350 (75.4%)
      patients with peripheral arthritis, 242 (52.1%) cases were monoarthritis.
      Furthermore the knee arthritis was seen in 148 (31.9%) patients and hip in 54
      (11.6) cases. Sacroiliitis was seen in 59 (12.7%) patients and spondylitis in 55
      (11.9%) cases. There were no significant differences regarding the occurrence of
      these focal lesions in both sexes. CONCLUSION: The results show that about one
      third of brucellosis in human is associated with skeletal complication.
      Peripheral arthritis, sacroiliitis and spondylitis are the frequent skeletal
      complications of human brucellosis.

PMID- 28503283
TI  - Cryptogenic hepatitis simulating cyst rupture and hydatid jaundice in a patient
      with preexisting asymptomatic hydatid cyst.
AB  - BACKGROUND: Rupture into the biliary ducts is the most frequent complication of
      hydatid liver disease. In endemic areas of Echinococcus granulosus, development
      of jaundice in a patient with liver cyst is initially suspected to have hydatid
      cyst. CASE PRESENTATION: A 48 year-old woman with history of asymptomatic hydatid
      liver cysts was admitted to the emergency department with right upper quadrant
      abdominal pain, increased levels of liver enzymes, bilirubin and alkaline
      phosphatase and the initial clinical diagnosis was the hydatid cyst rupture into
      the bile ducts. Surgery was planned but radiological evaluation (MRI) revealed
      non-dilated intra-extra biliary ducts. High suspicion of hydatid rupture required
      diagnostic ERCP that was normal and surgery was cancelled then. A possible
      diagnosis of coexistent hepatitis was suspected. Liver function tests normalized
      gradually and no cyst rupture was determined during surgery. CONCLUSION: These
      findings suggest considering the possible development of cryptogenic hepatitis in
      patients with preexisting hydatid cyst.

PMID- 28503284
TI  - Arteriovenous malformations of the colon: A report of two cases and review of the
      literature.
AB  - BACKGROUND: Arteriovenous malformations are one of the most common vascular
      disorders of the colon. Vascular disorders present as painless, high-volume
      rectal bleeding. CASE PRESENTATION: This study elucidates two rare cases of
      vascular disorders that are diagnosed as angiodysplasia of the left colon and
      cavernous hemangioma of the colon and rectum. The chief complaint in two patients
      was rectorrhagia. The patients who were diagnosed of ulcerative colitis were
      treated with sulfadiazine and prednisone. Due to continuous bleeding, the
      patients were referred to the surgery department for operation. The patients
      underwent total proctocolectomy. CONCLUSION: We discuss the faults in the
      diagnosis and management of vascular disorders of the intestine.

PMID- 28503285
TI  - Oral contraceptive-related transverse sinus thrombosis as an initial
      manifestation of antiphospholipid syndrome in the absence of systemic lupus
      erythematosus.
AB  - BACKGROUND: Cerebral venous sinus thrombosis is a rare and potentially life
      threatening neurologic manifestation of antiphospholipid syndrome. Oral
      contraceptive pills (OCP) may increase the risk of vascular events, even in
      people without family history of venous thrombosis. CASE PRESENTATION: A 31-year
      old woman with four weeks of constant headache and history of taking OCP for one
      year has been selected for this study. The results of magnetic resonance imaging
      (MRI) of brain and venography confirmed a diagnosis of cerebral venous sinus
      thrombosis. The serum anticardiolipin and antiphospholipid antibodies were
      elevated and a definitive diagnosis of antiphospholipid syndrome was made.
      CONCLUSION: The present report demonstrates the importance of screening for
      antiphospholipid antibodies in patients presenting with cerebral venous sinus
      thrombosis despite history of taking OCP.

PMID- 28503286
TI  - Fulminant hepatic failure due to metastatic choroidal melanoma.
AB  - BACKGROUND: Acute liver failure (ALF) as a consequence of metastatic disease is
      extremely uncommon. The liver is the most commonly affected organ by metastatic
      disease, but only a few cases of ALF in the setting of metastatic choroidal
      melanoma have been reported. CASE PRESENTATION: We describe the case of a 47-year
      old man with right upper quadrant pain, progressive jaundice, and unintentional
      weight loss. He also reported that he had experienced reduced left visual acuity
      which progressed to blindness over 2 months. On physical examination, we found a
      pigmented scleral lesion in the left eye. He had a coagulopathy and, during his
      hospital stay, he also developed encephalopathy. The diagnosis of ALF was
      therefore established and was later attributed to metastatic uveal melanoma. In
      addition, we briefly review the relevant literature. CONCLUSION: Liver metastasis
      should be kept in mind when assessing abnormal liver function tests in patients
      with uveal malignant melanoma.

PMID- 28503287
TI  - Time to appreciate Avicenna's knowledge of rabies.

PMID- 28503288
TI  - Geographical mortality distribution of cardiovascular diseases: First report from
      South Khorasan, Iran.

PMID- 28503289
TI  - The Three-Portal Technique in Arthroscopic Lateral Epicondylitis Release.
AB  - Lateral epicondylitis, commonly referred to as tennis elbow, is a syndrome
      characterized by pain over the origin of the common extensor muscles of the
      fingers, hand and wrist at the lateral epicondyle. Reports of 70-90% response to
      conservative treatment at one year have been documented in the literature though
      refractory cases often require surgical management. Arthroscopic treatment of
      lateral epicondylitis allows for intra-articular visualization for concomitant
      pathology and localization of the Extensor Carpi Radialis Brevis tendon.
      Additionally, compared to the open technique, the arthroscopic technique has a
      lower morbidity and an earlier return to work and activity. Here we describe a
      three portal technique for improved visualization in arthroscopic lateral
      epicondylitis release.

PMID- 28503290
TI  - Use of the Suprapatellar Approach in Intramedullary Nailing of a Multi
      Fragmentary Dislocated Tibia Fracture with a Hypermobile Intermediate Fragment in
      a Young Patient.
AB  - A case of an adolescent female patient who suffered from first grade open multi
      fragment fracture of the tibia (AO42-C2) with a large hypermobile intermediate
      fragment is presented in this case report. Intramedullary nailing of the tibia
      remains the treatment of choice despite a high risk of malformation and anterior
      knee pain especially in multi-fragment fractures. Here the suprapatellar approach
      as a semiextended nailing technique seems favorable. The specialty in our case
      was an early change of procedures necessary due to persistent swelling during
      external fixation based on the hypermobile intermediate fragment. Decision in
      favor of this surgical technique was conducted in order to achieve beneficial
      alignment and union while protecting the soft-tissue despite the hypermobile
      intermediate fragment and decrease the risk of anterior knee pain. In our case we
      achieved successful alignment and proper bone healing without any signs of
      anterior knee pain or limitations in the range of motion of the knee. With this
      report we would like to recommend the suprapatellar approach as a favorable
      alternative in intramedullary nailing in this type of fracture also in young
      patients.

PMID- 28503291
TI  - How many more? Sample size determination in studies of morphological integration
      and evolvability.
AB  - 1. The variational properties of living organisms are an important component of
      current evolutionary theory. As a consequence, researchers working on the field
      of multivariate evolution have increasingly used integration and evolvability
      statistics as a way of capturing the potentially complex patterns of trait
      association and their effects over evolutionary trajectories. Little attention
      has been paid, however, to the cascading effects that inaccurate estimates of
      trait covariance have on these widely used evolutionary statistics. 2. Here, we
      analyze the relationship between sampling effort and inaccuracy in evolvability
      and integration statistics calculated from 10-trait matrices with varying
      patterns of covariation and magnitudes of integration. We then extrapolate our
      initial approach to different numbers of traits and different magnitudes of
      integration and estimate general equations relating the inaccuracy of the
      statistics of interest to sampling effort. We validate our equations using a
      dataset of cranial traits, and use them to make sample size recommendations. 3.
      Our results suggest that highly inaccurate estimates of evolvability and
      integration statistics resulting from small sample sizes are likely common in the
      literature, given the sampling effort necessary to properly estimate them. We
      also show that patterns of covariation have no effect on the sampling properties
      of these statistics, but overall magnitudes of integration interact with sample
      size and lead to varying degrees of bias, imprecision, and inaccuracy. 4.
      Finally, we provide R functions that can be used to calculate recommended sample
      sizes or to simply estimate the level of inaccuracy that should be expected in
      these statistics, given a sampling design.

PMID- 28503292
TI  - Historical influence on the practice of chiropractic radiology: Part I - a survey
      of Diplomates of the American Chiropractic College of Radiology.
AB  - BACKGROUND: It is known that not all chiropractors follow mainstream guidelines
      on the use of diagnostic ionising radiation. Various reasons have been discussed
      in the literature, including using radiography to screen for congenital
      anomalies, to perform postural analysis, to search for contraindications to
      spinal manipulation, and to document chiropractic subluxations, i.e., tiny
      anatomical displacements of vertebrae thought to affect nerves and health. The
      visualisation of subluxations was the reason chiropractic first adopted the x-ray
      in 1910. There has never been a study of the influence of this historical
      paradigm of radiography on the practices of chiropractic radiologists (DACBRs or
      Diplomates of the American Chiropractic College of Radiology). METHODS: A survey
      was administered with a modified Dillman method using SurveyMonkey and
      supplemented by hard copies distributed at a professional conference. The target
      population was all active DACBRs. There were 34 items, which consisted of
      multiple choice and open-ended interrogatives on all three areas in which
      chiropractic radiologists work: education, clinical practice, and radiology
      practice. RESULTS: The response rate was 38% (73 of 190 DACBRs). Respondents
      reported that the historical paradigm of radiography was found in all areas of
      practice, but not as a major aspect. The majority of respondents did not condone
      that historical paradigm, but many tolerated it, particularly from referring
      chiropractors. Radiographic subluxation analysis was reportedly perpetuated by
      private clinical practitioners as well as technique instructors and supervising
      clinicians in the teaching institutions. CONCLUSIONS: Within the chiropractic
      profession, there is a continuing belief in radiographically visible subluxations
      as a cause of suboptimal health. This situation is sustained in part due to the
      reticence of other chiropractors to report these practices to licensing and
      registration boards. Investigation into other structures supporting a vitalistic
      belief system over science in chiropractic is recommended. In addition, it may be
      useful to explore remunerative systems that move beyond the inherently conflicted
      fee-for-service model.

PMID- 28503293
TI  - Historical influence on the practice of chiropractic radiology: part II -
      thematic analysis on the opinions of diplomates of the American Chiropractic
      College of Radiology about the future.
AB  - BACKGROUND: Over the past 20 years, various authors have addressed the question
      of the future of chiropractic. Most were positive about the future, with some
      advocating evidence-based practice and integration with mainstream healthcare,
      some advocating continued separation with an emphasis on subluxation-based care
      or the traditional/historical paradigm of chiropractic, and some calling for
      tolerance and unity. No papers were found specifically inquiring about the future
      of chiropractic radiology. METHODS: The study population consisted of all current
      members of the American Chiropractic College of Radiology (ACCR), estimated at
      190 people, known as chiropractic radiologists or Diplomates of the American
      Chiropractic Board of Radiology (DACBRs). An internet-based, anonymous survey
      using SurveyMonkey was implemented, supplemented by hard copies distributed at a
      conference. The main point of interest for this paper is the final item of the
      overall questionnaire. This item inquired about the future of chiropractic
      radiology. Thematic analysis was used on the responses, coded in both
      constructionist and inductive ways to extract both a general outlook and more
      specific themes. The inductive themes were also assigned secondarily to a SWOT
      (strengths, weaknesses, opportunities, and threats) analysis. RESULTS: The
      overall response rate to the survey was 38% (73/190); within the group of
      respondents, 71 of 73 (98%) answered the item that is the subject of this paper.
      Opinions on the outlook for chiropractic radiology in the future were more
      negative than positive, with 14 respondents giving a positive outlook, 26
      negative, and 14 non-committal. 28 respondents advocated integration with the
      wider healthcare community, 11 recommended emphasising separateness or a focus on
      working within chiropractic, and 15 did not express an opinion on this issue. Ten
      strengths were noted, 11 weaknesses, 57 opportunities, and 30 threats.
      CONCLUSIONS: The increasing necessity of demonstrating evidence for diagnostic
      and therapeutic procedures in healthcare makes it likely that chiropractic
      radiologists and the wider chiropractic profession will need to take a more
      active position on evidence-based practice. Re-evaluation of guidelines and
      legislation as well as enforcement policies and practices will be necessary. The
      consequences of failing to do so may include increased marginalisation and
      reduced viability as a profession.

PMID- 28503295
TI  - Building the infrastructure to make science metrics more scientific.
AB  - Research leaders, policy makers and science strategists need evidence to support
      decision-making around research funding investment, policy and strategy.  In
      recent years there has been a rapid expansion in the data sources available that
      shed light onto aspects of research quality, excellence, use, re-use and
      attention, and engagement. This is at a time when the modes and routes to share
      and communicate research findings and data are also changing.  In this opinion
      piece, we outline a series of considerations and interventions that are needed to
      ensure that research metric development is accompanied by appropriate scrutiny
      and governance, to properly support the needs of research assessors and decision
      makers, while securing the confidence of the research community. Key among these
      are: agreed 'gold standards' around datasets and methodologies; full transparency
      around the calculation and derivation of research-related indicators; and a
      strategy and roadmap to take the discipline of scientific indicators and research
      assessment to a more robust and sustainable place.

PMID- 28503294
TI  - A survey of free-ranging deer in Ireland for serological evidence of exposure to
      bovine viral diarrhoea virus, bovine herpes virus-1, bluetongue virus and
      Schmallenberg virus.
AB  - BACKGROUND: Deer are an important wildlife species in both the Republic of
      Ireland and Northern Ireland having colonised most regions across the island of
      Ireland. In comparison to cattle and sheep which represent the main farmed
      ruminant species on the island, there is a lack of data concerning their
      exposure, as measured by the presence of antibodies, to important viral pathogens
      of ruminants. A study was therefore undertaken to investigate the seroprevalence
      of wild deer to four viruses, namely bovine viral diarrhoea virus (BVDV), bovine
      herpesvirus-1 (BoHV-1), Schmallenberg virus (SBV) and bluetongue virus (BTV).
      RESULTS: Two panels of sera were assembled; Panel 1 comprised 259 samples (202
      collected in the Republic of Ireland and 57 in Northern Ireland) between 2013 and
      2015, while Panel 2 comprised 131 samples collected in the Republic of Ireland
      between 2014 and 2015. Overall sika deer (Cervus nippon) were sampled most
      commonly (54.8%), followed by fallow deer (Dama dama) (35.3%), with red deer
      (Cervus elaphus) (4.3%) and hybrid species (0.3%) sampled less frequently, with
      the species not being recorded for the remaining 5.3% of deer sampled. Age was
      not recorded for 96 of the 390 deer sampled. 196 of the remainder were adults,
      while 68 and 30 were yearlings and calves, respectively. Using commercially
      available enzyme-linked immunosorbent assays, true prevalence and 95% confidence
      intervals were calculated as 9.9%, (6.8-13.0% CI), SBV; 1.5% (0.1-3.0% CI), BoHV
      1; 0.0%, 0-1.7% CI), BVDV; and 0.0%, (0.01-0.10% CI), BTV. CONCLUSIONS: The
      results indicate a very low seroprevalence for both BVDV and BoHV-1 in the wild
      deer tested within the study and, are consistent with a very low prevalence in
      Ireland. While serological cross-reaction with cervid herpesviruses cannot be
      excluded, the results in both cases suggest that the presence of these viruses in
      deer is not a significant risk to their control and eradication from the cattle
      population. This is important given the ongoing programme to eradicate BVDV in
      Ireland and deliberations on a national eradication programme for BoHV-1. The SBV
      results show consistency with those reported from cattle and sheep on the island
      of Ireland, while the BTV results are consistent with this virus remaining exotic
      to Ireland. The results provide a baseline against which future surveys of either
      wild or farmed/captive deer populations can be compared.

PMID- 28503298
TI  - Patterns of ocular inflammation in patients with miliary tuberculosis.
AB  - BACKGROUND: Ocular morbidity associated with systemic tuberculosis is common. The
      clinical picture varies from anterior uveitis, intermediate uveitis and posterior
      uveitis to even panuveitis. There is little data on the correlation between
      specific systemic presentations and the ocular inflammation. We conducted a
      retrospective review of the ocular findings in the case records of patients
      admitted with a diagnosis of miliary tuberculosis. These patients were then
      referred for a more detailed ophthalmic evaluation. METHODS: We analysed the case
      records of patients with a clinical diagnosis of miliary tuberculosis over a 10
      year period at Lilavati Hospital  and Research Center, Mumbai. RESULTS: In total,
      11 immunocompetent patients were identified. All 22 eyes showed normal findings
      on slit lamp examination. Dilated fundus examination showed single or multiple
      tubercles. In our cohort, the ocular findings were exclusively in the form of
      choroidal tuberculosis, either unilaterally or bilaterally. Slit lamp examination
      revealed no anterior segment inflammation Conclusions: We suggest that this
      pattern of choroidal/retinal tuberculosis in the absence of anterior and
      intermediate segment inflammation is specific for miliary tuberculosis and may be
      related to a specific immune response.

PMID- 28491280
TI  - AR2, a novel automatic muscle artifact reduction software method for ictal EEG
      interpretation: Validation and comparison of performance with commercially
      available software.
AB  - Objective: To develop a novel software method (AR2) for reducing muscle
      contamination of ictal scalp electroencephalogram (EEG), and validate this method
      on the basis of its performance in comparison to a commercially available
      software method (AR1) to accurately depict seizure-onset location. Methods: A
      blinded investigation used 23 EEG recordings of seizures from 8 patients. Each
      recording was uninterpretable with digital filtering because of muscle artifact
      and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers
      assessed seizure-onset time, lateralization, and region, and specified confidence
      for each determination. The two methods were validated on the basis of the number
      of readers able to render assignments, confidence, the intra-class correlation
      (ICC), and agreement with other clinical findings. Results: Among the 23
      seizures, two-thirds of the readers were able to delineate seizure-onset time in
      10 of 23 using AR1, and 15 of 23 using AR2 (p<0.01). Fewer readers could
      lateralize seizure-onset (p<0.05). The confidence measures of the assignments
      were low (probable-unlikely), but increased using AR2 (p<0.05). The ICC for
      identifying the time of seizure-onset was 0.15 (95% confidence interval (CI),
      0.11-0.18) using AR1 and 0.26 (95% CI 0.21-0.30) using AR2.  The EEG
      interpretations were often consistent with behavioral, neurophysiological, and
      neuro-radiological findings, with left sided assignments correct in 95.9% (CI
      85.7-98.9%, n=4) of cases using AR2, and 91.9% (77.0-97.5%) (n=4) of cases using
      AR1. Conclusions: EEG artifact reduction methods for localizing seizure-onset
      does not result in high rates of interpretability, reader confidence, and inter
      reader agreement. However, the assignments by groups of readers are often
      congruent with other clinical data. Utilization of the AR2 software method may
      improve the validity of ictal EEG artifact reduction.

PMID- 28503299
TI  - DangerTrack: A scoring system to detect difficult-to-assess regions.
AB  - Over recent years, multiple groups have shown that a large number of structural
      variants, repeats, or problems with the underlying genome assembly have dramatic
      effects on the mapping, calling, and overall reliability of single nucleotide
      polymorphism calls. This project endeavored to develop an easy-to-use track for
      looking at structural variant and repeat regions. This track, DangerTrack, can be
      displayed alongside the existing Genome Reference Consortium assembly tracks to
      warn clinicians and biologists when variants of interest may be incorrectly
      called, of dubious quality, or on an insertion or copy number expansion. While
      mapping and variant calling can be automated, it is our opinion that when these
      regions are of interest to a particular clinical or research group, they warrant
      a careful examination, potentially involving localized reassembly. DangerTrack is
      available at https://github.com/DCGenomics/DangerTrack.

PMID- 28503297
TI  - Cardiovascular involvement and manifestations of systemic Chikungunya virus
      infection: A systematic review.
AB  - BACKGROUND: In the last three years, chikungunya virus disease has been
      spreading, affecting particularly the Americas, producing more than two million
      cases. In this setting, not only new disease-related epidemiological patterns
      have been found, but also new clinical findings have been reported by different
      research groups. These include findings on the cardiovascular system, including
      clinical, electrocardiographic and echocardiographic alterations. METHODS: We
      performed a systematic review looking for reports about cardiovascular compromise
      during chikungunya disease. Cardiac compromise is not so common in isolated
      episodes; but countries where chikungunya virus is an epidemic should be well
      informed about this condition. We used 6 bibliographical databases as resources:
      Medline/Pubmed, Embase, ScienceDirect, ClinicalKey, Ovid and SciELO. Dengue
      reports on cardiovascular affectation were included as well, to compare both
      arbovirus' organic affectations. Articles that delved mainly into the rheumatic
      articular and cutaneous complications were not considered, as they were not in
      line with the purpose of this study. The type of articles included were reviews,
      meta-analyses, case-controls, cohort studies, case reports and case series.
      RESULTS: Originally based on 737 articles, our reviewed selected 40 articles with
      54.2% at least mentioning CHIKV cardiovascular compromise within the systemic
      affectation. Cardiovascular manifestations can be considered common and have been
      reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA,
      including mainly, but no limited to: hypotension, shock and circulatory collapse,
      Raynaud phenomenon, arrhythmias, murmurs, myocarditis, dilated cardiomyopathy,
      congestive insufficiency, heart failure and altered function profile (Troponins,
      CPK). CONCLUSIONS: Physicians should be encouraged to keep divulgating reports on
      the cardiovascular involvement of chikungunya virus disease, to raise awareness
      and ultimately encourage suitable diagnosis and intervention worldwide.

PMID- 28503300
TI  - How to decrease bronchopulmonary dysplasia in your neonatal intensive care unit
      today and "tomorrow".
AB  - Bronchopulmonary dysplasia, or BPD, is the most common chronic lung disease in
      infants. Genetic predisposition and developmental vulnerability secondary to
      antenatal and postnatal infections, compounded with exposure to hyperoxia and
      invasive mechanical ventilation to an immature lung, result in persistent
      inflammation, culminating in the characteristic pulmonary phenotype of BPD of
      impaired alveolarization and dysregulated vascularization. In this article, we
      highlight specific areas in current management, and speculate on therapeutic
      strategies that are on the horizon, that we believe will make an impact in
      decreasing the incidence of BPD in your neonatal intensive care units.

PMID- 28503301
TI  - Is there a role for ischaemic conditioning in cardiac surgery?
AB  - Coronary artery disease (CAD) is a major cause of morbidity and mortality
      worldwide. Coronary artery bypass graft (CABG) surgery is the revascularisation
      strategy of choice in patients with diabetes mellitus and complex CAD. Owing to a
      number of factors, including the ageing population, the increased complexity of
      CAD being treated, concomitant valve and aortic surgery, and multiple
      comorbidities, higher-risk patients are being operated on, the result of which is
      an increased risk of sustaining perioperative myocardial injury (PMI) and poorer
      clinical outcomes. As such, new treatment strategies are required to protect the
      heart against PMI and improve clinical outcomes following cardiac surgery. In
      this regard, the heart can be endogenously protected from PMI by subjecting the
      myocardium to one or more brief cycles of ischaemia and reperfusion, a strategy
      called "ischaemic conditioning". However, this requires an intervention applied
      directly to the heart, which may be challenging to apply in the clinical setting.
      In this regard, the strategy of remote ischaemic conditioning (RIC) may be more
      attractive, as it allows the endogenous cardioprotective strategy to be applied
      away from the heart to the arm or leg by simply inflating and deflating a cuff on
      the upper arm or thigh to induce one or more brief cycles of ischaemia and
      reperfusion (termed "limb RIC"). Although a number of small clinical studies have
      demonstrated less PMI with limb RIC following cardiac surgery, three recently
      published large multicentre randomised clinical trials found no beneficial
      effects on short-term or long-term clinical outcomes, questioning the role of
      limb RIC in the setting of cardiac surgery. In this article, we review ischaemic
      conditioning as a therapeutic strategy for endogenous cardioprotection in
      patients undergoing cardiac surgery and discuss the potential reasons for the
      failure of limb RIC to improve clinical outcomes in this setting. Crucially, limb
      RIC still has the therapeutic potential to protect the heart in other clinical
      settings, such as acute myocardial infarction, and it may also protect other
      organs against acute ischaemia/reperfusion injury (such as the brain, kidney, and
      liver).

PMID- 28503304
TI  - Clinico- pathologic presentation of hypersensitivity pneumonitis in Egyptian
      patients: a multidisciplinary study.
AB  - BACKGROUND: Hypersensitivity pneumonitis (HP) is a common diffuse parenchymal
      lung disease in Egypt which can be difficult to recognize due to the dynamic
      symptoms & associated environmental factors. METHODS: Forty-three Egyptian
      patients were enrolled in this study, presenting with dyspnea and cough,
      predominant ground-glass opacity (GGO) in high-resolution computed tomography
      (HRCT) where lung biopsy was needed to establish the diagnosis. RESULTS: The age
      range was 15 to 60 years. Females represented 90.7% (39 patients) while 9.3% (4
      patients) of our patients were males. History of contact with birds was detected
      in 9 (20.9%) patients. Most of our patients (60.5%) didn't have exposure history,
      and only 8 patients (18.6%) were living in geographic areas in Egypt that are
      known for the exposure to environmental etiologic factors (cane sugar exhaust
      fumes). The most common HRCT pattern was GGO with mosaic parenchyma in 18
      patients (41.86%), followed by GGO with centrilobular nodules in 9 patients
      (20.93%), then isolated diffuse GGO in 5 patients (11.62%), GGO with traction
      bronchiectasis in 4 patients (9.3%), GGO with consolidation in 3 patients
      (6.97%), GGO with reticulations in 2 patients (4.65%), and GGO with cysts in 2
      patients (4.65%). The most common histologic finding was isolated multinucleated
      giant cells in 38 patients (88.3%) commonly found in airspaces (24 patients) and
      less commonly in the interstitium (14 patients), followed by interstitial
      pneumonia and cellular bronchiolitis in 36 patients (83.7% each), interstitial
      ill-formed non-necrotizing granulomas in 12 patients (27.9%), fibrosis in 10
      patients (23.2%), and organizing pneumonia pattern in 4 patients (9.3%).
      CONCLUSION: The diagnosis of HP presenting with predominant GGO pattern in HRCT
      requires a close interaction among clinicians, radiologists, and pathologists.
      Some environmental and household factors may be underestimated as etiologic
      factors. Further environmental and genetic studies are needed especially in
      patients with negative exposure history.

PMID- 28503302
TI  - Reliability and validity of using telephone calls for post-discharge surveillance
      of surgical site infection following caesarean section at a tertiary hospital in
      Tanzania.
AB  - BACKGROUND: Surgical site infection (SSI) is a common post-operative complication
      causing significant morbidity and mortality. Many SSI occur after discharge from
      hospital. Post-discharge SSI surveillance in low and middle income countries
      needs to be improved. METHODOLOGY: We conducted an observational cohort study in
      Dodoma, Tanzania to examine the sensitivity and specificity of telephone calls to
      detect SSI after discharge from hospital in comparison to a gold standard of
      clinician review. Women undergoing caesarean section were enrolled and followed
      up for 30 days. Women providing a telephone number were interviewed using a
      structured questionnaire at approximately days 5, 12 and 28 post-surgery. Women
      were then invited for out-patient review by a clinician blinded to the findings
      of telephone interview. RESULTS: A total of 374 women were enrolled and an
      overall SSI rate of 12% (n = 45) was observed. Three hundred and sixteen (84%)
      women provided a telephone number, of which 202 had at least one telephone
      interview followed by a clinical review within 48 h, generating a total of 484
      paired observations. From the clinical reviews, 25 SSI were diagnosed, of which
      telephone interview had correctly identified 18 infections; telephone calls did
      not incorrectly identify SSI in any patients. The overall sensitivity and
      specificity of telephone interviews as compared to clinician evaluation was 72
      and 100%, respectively. CONCLUSION: The use of telephone interview as a
      diagnostic tool for post-discharge surveillance of SSI had moderate sensitivity
      and high specificity in Tanzania. Telephone-based detection may be a useful
      method for SSI surveillance in low-income settings with high penetration of
      mobile telephones.

PMID- 28503305
TI  - Three Dimensional Conjugation of Recombinant N-Cadherin to a Hydrogel for In
      Vitro Anisotropic Neural Growth.
AB  - Living cells are extensively being studied to build functional tissues that are
      useful for both fundamental and applied bioscience studies. Increasing evidence
      suggests that cell-cell adhesion controlled by intercellular cadherin junction
      plays important roles in the quality of the resulting engineered tissue. These
      findings prompted efforts to interrogate biological effects of cadherin at a
      molecular scale; however, few efforts were made to harness the effects of
      cadherin on cells cultured in an in vivo-like three dimensional matrix. To this
      end, this study reports a hydrogel matrix three dimensionally functionalized with
      a controlled number of Fc-tagged recombinant N-cadherins (N-Cad-Fc). To retain
      the desired conformation of N-Cad, these cadherins were immobilized and oriented
      to the gel by anti-Fc-antibodies chemically coupled to gels. The gels were
      processed to present N-Cad-Fc in uniaxially aligned microchannels or randomly
      oriented micropores. Culturing cortical cells in the functionalized gels
      generated a large fraction of neurons that are functional as indicated by
      increased intracellular calcium ion concentrations with the microchanneled gel.
      In contrast, direct N-Cad-Fc immobilization to microchannel or micropore walls of
      the gel limited the growth of neurons and increased the glial to neuron ratio.
      The results of this study will be highly useful to organize a wide array of
      cadherin molecules in a series of biomaterials used for three-dimensional cell
      culture and to regulate phenotypic activities of tissue-forming cells in an
      elaborate manner.

PMID- 28503303
TI  - A study on HIV, Syphilis, and Hepatitis B and C virus infections among female sex
      workers in the Republic of Congo.
AB  - BACKGROUND: Female Sex Workers (FSWs) are considered to be at high risk for
      transmission of Sexually Transmitted Infections (STIs) and are defined as a
      priority of the national HIV/AIDS response in the Republic of Congo (RoC).
      However, no data are available regarding STIs in this group. This study aimed to
      determine the prevalences of HIV, syphilis and hepatitis B and C among FSWs in
      five cities in the country. METHODS: A cross-sectional study was conducted from
      November 2nd 2011 to May 15th 2012. Participants were recruited in Brazzaville,
      Pointe-Noire, Dolisie, Nkayi and Pokola using a respondent-driven sampling
      method. RESULTS: A total of 805 FSWs were recruited with an average age of 28.31
      +/- 9.15 years. The overall prevalences of HIV, syphilis, HBV and HCV were 7.50%,
      2.20%, 4.20% and 0.70%, respectively. The age groups 35-39 (20.51% [0%-36.93%], p
      = 0.0057) and greater than 40 years (16.67% [0%-34.93%], P = 0.016) were
      positively associated with behaviors at high risk of HIV infection. For syphilis,
      the most infected age group was the one greater than 40 years, at 6.25% ([1.06% 
      72.37%] p = 0.04). Pointe-Noire was the most infected city for syphilis and HBV,
      with 5.15% (p = 0.0061) and 4.22% (p?0.001), respectively. No risk factors were
      associated with HCV infection. FSWs practicing in mobile prostitution sites had a
      significantly higher infection rate (2.1% [0%-11.09%] p = 0.04). CONCLUSION: This
      study shows that the prevalence of HIV and other STIs in FSWs is high. Therefore,
      a combination of individual and structural interventions could reduce the risk of
      an STI "reservoir" among this population.

PMID- 28503306
TI  - The drive to generate multiple forms of oncogenic cyclin D1 transcripts in mantle
      cell lymphoma.
AB  - Alternative polyadenylation is a rapidly emerging form of gene regulation, which
      in its simplest form, enables the generation of mRNA transcripts that code for
      the same protein but have 3'UTRs of different lengths and regulatory content. For
      oncogenes, shorter 3'UTRs would be preferred as a mechanism to evade miRNA
      regulation. The shortening of the 3'UTR of cyclin D1 in mantle cell lymphoma
      offers provocative insights into this process. Patient samples have revealed that
      3'UTR shortening may occur due to mutations, or translocations that result in the
      generation of a chimeric 3'UTR. The truncated cyclin D1 3'UTRs resulting from
      alternative polyadenylation, use a premature canonical polyadenylation signal
      close to the stop codon that was generated either as a result of mutations or
      provided by another gene in the chimeric 3'UTR. The sequence of the
      polyadenylation signal in mantle cell lymphoma appears to be critical for 3'end
      formation of the cyclin D1 transcript. Shortening the 3'UTR allows cyclin D1 to
      potentially evade regulation by over 80 miRNAs that are predicted to bind to its
      full length 3'UTR.

PMID- 28503307
TI  - Clinical significance of intronic variants in BRAF inhibitor resistant melanomas
      with altered BRAF transcript splicing.
AB  - Alternate BRAF splicing is the most common mechanism of acquired resistance to
      BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4-8 splicing
      was shown to involve an intronic mutation, located 51 nucleotides upstream of
      BRAF exon 9 within a predicted splicing branch point. This intronic mutation was
      identified in a single cell line but has not been examined in vivo. Herein we
      demonstrate that in three melanomas biopsied from patients with acquired
      resistance to BRAF inhibitors, alternate BRAF exon 4-8 splicing is not associated
      with this intronic branch point mutation. We also confirm that melanoma cells
      expressing BRAF splicing variants retain exquisite sensitivity to existing FDA
      approved MEK inhibitors.

PMID- 28503308
TI  - Portal hypertension as the initial manifestation of POEMS syndrome: a case
      report.
AB  - BACKGROUND: Portal hypertension has a broad differential diagnosis. POEMS
      syndrome is an uncommon cause of it. POEMS syndrome is a rare disease involving
      multiple organs. In differential diagnosis of portal hypertension, POEMS syndrome
      should be considered especially when other symptoms such as numbness,
      organomegaly, endocrine alteration and skin changes also present, as it is
      highlighted by our case. CASE PRESENTATION: We report a 46-year-old Chinese male,
      a teacher, presenting with portal hypertension. Electromyography revealed
      peripheral neuropathy. Immunofixation showed monoclonal immunoglobulin A lambda
      protein. The diagnosis of POEMS syndrome was established. After treatment of
      lenalidomide combined with dexamethasone over 2 years, the patient achieved a
      considerable improvement. CONCLUSION: This case highlights the manifestation of
      portal hypertension in POEMS syndrome. Lenalidomide with or without dexamethasone
      is effective for portal hypertension due to POEMS syndrome, though esophageal and
      gastric varices seems not reversible so easily.

PMID- 28503309
TI  - Are there two forms of isometric muscle action? Results of the experimental study
      support a distinction between a holding and a pushing isometric muscle function.
AB  - BACKGROUND: In isometric muscle function, there are subjectively two different
      modes of performance: one can either hold isometrically - thus resist an
      impacting force - or push isometrically - therefore work against a stable
      resistance. The purpose of this study is to investigate whether or not two
      different isometric muscle actions - the holding vs. pushing one (HIMA vs PIMA) -
      can be distinguished by objective parameters. METHODS: Ten subjects performed two
      different measuring modes at 80% of MVC realized by a special pneumatic system.
      During HIMA the subject had to resist the defined impacting force of the
      pneumatic system in an isometric position, whereby the force of the cylinder
      works in direction of elbow flexion against the subject. During PIMA the subject
      worked isometrically in direction of elbow extension against a stable position of
      the system. The signals of pressure, force, acceleration and mechanomyography/
      tendography (MMG/MTG) of the elbow extensor (MMGtri/MTGtri) and the abdominal
      muscle (MMGobl) were recorded and evaluated concerning the duration of
      maintaining the force level (force endurance) and the characteristics of MMG-/MTG
      signals. Statistical group differences comparing HIMA vs. PIMA were estimated
      using SPSS. RESULTS: Significant differences between HIMA and PIMA were
      especially apparent regarding the force endurance: During HIMA the subjects
      showed a decisively shorter time of stable isometric position (19 +/- 8 s) in
      comparison with PIMA (41 +/- 24 s; p = .005). In addition, during PIMA the
      longest isometric plateau amounted to 59.4% of the overall duration time of
      isometric measuring, during HIMA it lasted 31.6% (p = .000). The frequency of
      MMG/MTG did not show significant differences. The power in the frequency ranges
      of 8-15 Hz and 10-29 Hz was significantly higher in the MTGtri performing HIMA
      compared to PIMA (but not for the MMGs). The amplitude of MMG/MTG did not show
      any significant difference considering the whole measurement. However, looking
      only at the last 10% of duration time (exhaustion), the MMGtri showed
      significantly higher amplitudes during PIMA. CONCLUSION: The results suggest that
      under holding isometric conditions muscles exhaust earlier. That means that there
      are probably two forms of isometric muscle action. We hypothesize two potential
      reasons for faster yielding during HIMA: (1) earlier metabolic fatigue of the
      muscle fibers and (2) the complexity of neural control strategies.

PMID- 28503310
TI  - Individual capacity-building approaches in a global pharmaceutical systems
      strengthening program: a selected review.
AB  - BACKGROUND: Medicines use related challenges such as inadequate adherence, high
      levels of antimicrobial resistance and preventable adverse drug reactions have
      underscored the need to incorporate pharmaceutical services to help achieve
      desired treatment outcomes, and protect patients from inappropriate use of
      medicines. This situation is further constrained by insufficient numbers of
      pharmaceutical personnel and inappropriate skill mix. Studies have addressed
      individual capacity building approaches of logistics, supply chain or disease
      specific interventions but few have documented those involving such pharmacy
      assistants/professionals, or health workers/professionals charged with improving
      access and provision of pharmaceutical services. We examined how different
      training modalities have been employed and adapted to meet country-specific
      context and needs by a global pharmaceutical systems strengthening program in
      collaboration with a country's Ministry of Health and local stakeholders.
      METHODS: Structured, content analysis of training approaches from twelve selected
      countries and a survey among conveniently selected trainees in Bangladesh and
      Ethiopia. RESULTS: Case-based learning, practice and feedback, and repetitive
      interventions such as post-training action plan, supportive supervision and
      mentoring approaches are effective, evidence-based training techniques. In
      Ethiopia and Bangladesh, over 94% of respondents indicated that they have
      improved or developed skills or competencies as a result of the program's
      training activities. Supportive supervision structures and mentorship have been
      institutionalized with appropriate management structures. National authorities
      have been sensitized to secure funding from domestic resources or from the global
      fund grants for post-training follow-up initiatives. The Pharmaceutical
      Leadership Development Program is an effective, case-based training modality that
      motivates staff to develop quality-improvement interventions and solve specific
      challenges. Peer-to-peer learning mechanisms than traditional didactic methods
      was a preferred intervention among high level government officials both within
      country and between countries. CONCLUSION: Interventions must involve local
      institutions in the design and delivery of content for both pre-service and in
      service training as well as web-based methods where feasible. Such efforts would
      meet the changing demand in the pharmaceutical system, and promote the ownership
      of the human capacity development interventions. The cost-effective partnership
      with universities demonstrate that competency based pre-service training will
      prepare the future pharmaceutical workforce with a critical foundation of
      knowledge and skills required to meet the growing demand for patient-centered
      pharmaceutical services in resource-constrained countries.

PMID- 28503311
TI  - A community resource for exploring and utilizing genetic diversity in the USDA
      pea single plant plus collection.
AB  - Globally, pea (Pisum sativum L.) is an important temperate legume crop for food,
      feed and fodder, and many breeding programs develop cultivars adapted to these
      end-uses. In order to assist pea development efforts, we assembled the USDA Pea
      Single Plant Plus Collection (PSPPC), which contains 431 P. sativum accessions
      with morphological, geographic and taxonomic diversity. The collection was
      characterized genetically in order to maximize its value for trait mapping and
      genomics-assisted breeding. To that end, we used genotyping-by-sequencing-a cost
      effective method for de novo single-nucleotide polymorphism (SNP) marker
      discovery-to generate 66 591 high-quality SNPs. These data facilitated the
      identification of accessions divergent from mainstream breeding germplasm that
      could serve as sources of novel, favorable alleles. In particular, a group of
      accessions from Central Asia appear nearly as diverse as a sister species, P.
      fulvum, and subspecies, P. sativum subsp. elatius. PSPPC genotypes can be paired
      with new and existing phenotype data for trait mapping; as proof-of-concept, we
      localized Mendel's A gene controlling flower color to its known position. We also
      used SNP data to define a smaller core collection of 108 accessions with similar
      levels of genetic diversity as the entire PSPPC, resulting in a smaller germplasm
      set for research screening and evaluation under limited resources. Taken
      together, the results presented in this study along with the release of a
      publicly available SNP data set comprise a valuable resource for supporting
      worldwide pea genetic improvement efforts.

PMID- 28503312
TI  - Germline and somatic genetic changes in multicentric tumors obtained from a
      patient with multiple endocrine neoplasia type 1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused
      by germline mutations of the MEN1 gene located in chromosome 11q13. In patients
      with MEN1, multicentric tumors develop in the involved organs; however, precise
      evaluation of genetic changes in these multicentric tumors has not been
      performed. In the present study, using whole-exome sequencing, we analyzed
      germline and somatic genetic changes in blood cells, two pancreatic endocrine
      tumors and one duodenal tumor obtained from a patient with MEN1 gastrinoma. We
      found that this patient possessed a novel germline mutation of the MEN1 gene
      [NM_137099.2:c.1505dupA (p.Lys502Lysfs); the localization was Chr11:64572134 on
      Assembly GRCh37], in which an adenine insertion in codon 502 of the MEN1 gene
      resulted in a frame shift and a premature stop codon. In terms of heterozygosity,
      the mutated allele was heterozygous in blood cells, hemizygous in the two
      pancreatic tumors and homozygous in the duodenal tumor. Immunohistochemical
      staining confirmed that only truncated menin protein accumulated in the nucleus
      of the tumor tissues. Further evaluation of tumor-specific somatic mutations in
      two pancreatic tumors did not detect single-nucleotide variations (SNVs) in 609
      cancer-associated genes designated by the COSMIC cancer gene census, suggesting
      that the germline MEN1 mutation and resultant loss of heterozygosity played a
      major role in tumorigenesis. In the duodenal tumor, in addition to the germline
      MEN1 mutation, single-nucleotide variations in two cancer-associated genes were
      found. Further studies are required to clarify the role of these somatic single
      nucleotide variations in the progression of MEN1 tumors.

PMID- 28503313
TI  - Novel DHCR7 mutation in a case of Smith-Lemli-Opitz syndrome showing 46,XY
      disorder of sex development.
AB  - Smith-Lemli-Opitz syndrome is an autosomal recessive disease caused by mutations
      in 7-dehydrocholesterol reductase (DHCR7), which is rarely observed in Japan. We
      report a Japanese case with 46,XY disorder of sex development and Y-shaped 2-3
      toe syndactyly. DHCR7 gene analysis revealed compound heterozygous mutations
      including the novel mutation H442R. Early diagnosis led to starting cholesterol
      treatment at an early age.

PMID- 28503314
TI  - Atypical teratoid/rhabdoid tumor of lumbar spine in a toddler child.
AB  - BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare pediatric central
      nervous system malignancy with poor outcome. AT/RT is infrequently located in the
      spinal cord. CLINICAL PRESENTATION: A 16-month-old boy presented with progressive
      urinary retention and weakness of the lower extremities. Magnetic resonance
      imaging of the spine revealed an intradural extramedullary mass occupying the
      spinal canal at the level of T10-L3. The tumor was successfully resected by using
      neuroendoscopy. Histopathology demonstrated rhabdoid cells with eccentric nuclei
      and eosinophilic cytoplasmic hyaline inclusions. Immunohistologically, the tumor
      cells showed positive for epithelial membrane antigen, vimentin and neuron
      specific enolase, and negative for integrase interactor 1. After surgery, the
      patient showed significant improvement in sitting and other neurological signs
      but presenting with flaccid neurogenic bladder. Intrathecal chemotherapy under
      European Rhabdoid Registry (EU-RHAB) protocol with Doxorubicin, Carboplatin,
      Etoposide, Ifosfamide, Vincristine, Cyclophosphamide and Actinomycin-D was given.
      However, recurrent intradural extramedullary tumor at the level of T11-L2
      developed in 3 months. CONCLUSION: We report a young Asian case of AT/RT in
      thoracolumbar spine with recurrent tumor shortly after complete surgical
      resection of the tumor.

PMID- 28503315
TI  - 'Problematic methodology'.

PMID- 28503316
TI  - Recovery of supraspinal control of leg movement in a chronic complete flaccid
      paraplegic man after continuous low-frequency pelvic nerve stimulation and FES
      assisted training.
AB  - INTRODUCTION: More than 30 years ago, functional electrical stimulation (FES) was
      developed as an orthotic system to be used for rehabilitation for SCI patients.
      In the present case report, FES-assisted training was combined with continuous
      low-frequency stimulation of the pelvic somatic nerves in a SCI patient. CASE
      PRESENTATION: We report on unexpected findings in a 41-year-old man with chronic
      complete flaccid paraplegia, since he was 18 years old, who underwent spinal stem
      cell therapy and a laparoscopic implantation of neuroprosthesis (LION procedure)
      in the pelvic lumbosacral nerves. The patient had complete flaccid sensomotoric
      paraplegia T12 as a result of a motor vehicle accident in 1998. In June 2011, he
      underwent a laparoscopic implantation of stimulation electrodes to the sciatic
      and femoral nerves for continuous low-frequency electrical stimulation and
      functional electrical stimulation of the pelvic nerves. Neither intraoperative
      direct stimulation of the pelvic nerves nor postoperative stimulation induced any
      sensation or muscle reactions. After 2 years of passive continuous low-frequency
      stimulation, the patient developed progressive recovery of electrically assisted
      voluntary motor functions below the lesions: he was first able to extend the
      right knee and 6 months later, the left. He is currently capable of voluntary
      weight-bearing standing and walking (with voluntary knee movements) about 50 m
      with open cuff crutches and drop foot braces. DISCUSSION: Our findings suggest
      that continuous low-frequency pelvic nerve stimulation in combination with FES
      assisted training might induce changes that affect both the upper and the lower
      motor neuron and allow supra- and infra-spinal inputs to engage residual spinal
      and peripheral pathways.

PMID- 28503317
TI  - Diagnostic accuracy of single channel cystometry for neurogenic bladder diagnosis
      following spinal cord injury: a pilot study.
AB  - INTRODUCTION: This is a cross-sectional study of 1 year duration (August 2013 to
      August 2014). The objective of the study was to investigate the diagnostic
      accuracy of single channel cystometry (SCC) for confirmation of neurogenic
      bladder following spinal cord injury. MATERIALS AND METHODS: The study was
      conducted in both out-patient and in-patient services of Department of
      Rehabilitation Medicine, Hospital Sungai Buloh, Malaysia. Subjects in the study
      include sixteen patients with a clinical diagnosis of neurogenic bladder
      following spinal cord injury aged between 15 and 62 years. Patients with a
      clinical diagnosis of neurogenic bladder were subjected to cystometric evaluation
      using SCC in our hospital. Confirmation of the diagnosis was made by urodynamic
      study (UDS) in another hospital. SCC procedure involved manual intra-vesical
      pressure assessment using a 12F Nelaton catheter. Cystometric parameter
      measurement taken in this study was detrusor pressure (cm H2O) done at regular
      intervals from baseline, throughout bladder filling phase and voiding/leaking
      phase. The relationship between detrusor pressure to bladder volume from initial
      bladder filling until voiding or leaking phase was recorded, analyzed and graph
      plotted. Maximum detrusor pressure (cm H2O) during bladder filling, voiding or
      leaking and the maximum cystometric capacity (mls) was recorded. RESULTS: SCC was
      found to have 100% sensitivity, 50% specificity, 93.33% positive predictive value
      and 100% negative predictive value for neurogenic bladder diagnosis. Only 55.55%
      patients with SCC suspicion of detrusor sphincter dyssynergia (DSD) had
      comparable UDS findings. DISCUSSION: The use of SCC may be considered for
      objective confirmation of neurogenic bladder diagnosis following spinal cord
      lesion in centers with limited access to UDS. However, we are not able to
      establish its clinical application for confirmation of DSD.

PMID- 28503318
TI  - Erratum: Against the odds: extraordinary recovery from complete cauda equina
      syndrome following L3 fracture. Time still matters.
AB  - [This corrects the article DOI: 10.1038/scsandc.2016.27.].

PMID- 28503319
TI  - An unexpected delivery: pregnancy experience of a paraplegic lady.
AB  - INTRODUCTION: Spinal cord injury (SCI) has increased over the years, and so has
      the survival. Women with SCI remain fertile and have equal chance of pregnancy.
      CASE PRESENTATION: We described a case of a 29-year-old lady with traumatic
      spinal cord injury (SCI) resultant with paraplegia in 2008, who conceived
      naturally 2 years after the injury. She only had her antenatal check-up at a low
      risk antenatal center throughout her pregnancy and was not referred to
      specialized obstetric care. She did not appreciate active labor, and unexpectedly
      had a precipituous labor and gave birth in the bathroom. DISCUSSION: Pregnancy is
      relatively safe in women with spinal cord injury (SCI). However, disability
      related issues can be exaggerated during pregnancy, delivery and post-partum
      periods. Thus, understanding common issues related to pregnancy in this
      population is important. Specialized obstetric care with rehabilitation input
      throughout antenatal and postnatal care is crucial for a good overall outcome of
      a pregnant woman with SCI.

PMID- 28503320
TI  - Subacute posttraumatic ascending myelopathy: a literature review.

PMID- 28503321
TI  - Response to comment on subacute post-traumatic ascending myelopathy: a literature
      review.

PMID- 28503322
TI  - Changes in oxidized LDL during a half marathon in athletes with spinal cord
      injuries.
AB  - INTRODUCTION: We reported previously that exercise significantly increases plasma
      adrenaline and oxidized low-density lipoprotein (oxLDL) in healthy subjects but
      not in persons with spinal cord injury (SCI). Since oxLDL and adrenaline levels
      are associated with oxidant/antioxidant balance, and exercise training elicits
      production of reactive oxygen species, we elucidated the effects of exercise on
      adrenaline, oxidant/antioxidant balance and oxLDL in individuals with SCI. CASE
      PRESENTATION: Eight subjects with cervical spinal cord injury (CSCI) and nine
      subjects with lower lesion of SCI (lower SCI (LSCI)) participated in a wheelchair
      half marathon race, and blood samples were collected before (pre), immediately
      after (post) and 1 h after the race (post 1 h). The blood samples were used to
      determine adrenaline, derivatives of reactive oxygen metabolites (d-ROMs) and
      biological antioxidant potential (BAP), both as markers for oxidant/antioxidant
      balance. DISCUSSION: Pre-serum oxLDL levels were 147.2+/-8.1 and 97.0+/-10.4 U l
      1 (mean+/-s.e.m.) in LCSI and CSCI subjects, respectively, and remained stable
      throughout the study. Adrenaline levels were higher in LSCI athletes than in CSCI
      athletes, especially post half marathon. Serum d-ROMs level did not change
      between pre and post in both groups. The mean BAP was significantly higher in
      LSCI than in CSCI subjects (2574+/-94.6 vs 2118+/-94.6 MUmol l-1) at post,
      whereas the oxidative stress index (d-ROMs/BAP) was similar in the two groups
      throughout the study. In conclusion, exercise did not increase the d-ROMs or d
      ROMs/BAP ratio in CSCI and LSCI subjects. The lack of increase in the plasma
      oxLDL level in SCI subjects was not due to the lack of response of adrenaline to
      exercise.

PMID- 28503323
TI  - Severe cervical flexion myelopathy with long tract signs: a case report and a
      review of literature.
AB  - INTRODUCTION: Hirayama disease, a type of cervical flexion myelopathy, is a rare
      neurological disease characterized by muscular atrophy of the forearms and hands.
      Generally, the pathology is limited to the gray matter of the anterior horns in
      the lower cervical spinal cord. However, in rare cases the damage can spread to
      the white matter and present as long tract signs. CASE PRESENTATION: We report on
      a 30-year-old female whose onset presented as unilateral muscle atrophy of the
      right hand in her teens. Despite conservative treatment using a cervical collar,
      she developed prolonged bilateral muscle atrophy, sensory disturbance and spastic
      gait, along with bladder and rectal disturbances. Her hands were frozen into a
      'claw-like' gesture and her intrinsic muscles were highly atrophic. She was
      unable to unclench her hands. Although the space available for the spinal cord
      was large, the spinal cord was highly atrophic. She had local kyphosis with a
      large (61 degrees ) flexion range of motion. During flexion the spinal cord was
      stretched, resulting in contact with the posterior wall of the vertebrae.
      Posterior fusion surgery was performed to prevent progression of the myelopathy.
      After surgery, she gained mild improvement in both muscle strength and her hand's
      movement. However, her spastic gait and muscle atrophy remained. DISCUSSION: Most
      cases of cervical flexion myelopathy as represented by Hirayama disease have a
      self-limiting benign prognosis. However, some cases can develop advanced
      myelopathy with long tract signs. Long-term follow-up is recommended for these
      cases because they may require early surgical treatment.

PMID- 28503324
TI  - A 5-day antibiotic course for treatment of intermittent catheter-associated
      urinary tract infection in patients with spinal cord injury.
AB  - INTRODUCTION: This was a retrospective monocentric study conducted at Centre
      Calve, France, with the objective of evaluating the effectiveness of a 5-day
      course of antibiotics for symptomatic (mild urinary tract infection, UTI) or
      asymptomatic (aBact) bacteriuria in patients with spinal cord injury on
      intermittent catheterization. CASE PRESENTATION: This study was conducted from
      May 2013 to September 2016. Antibiotic selection always followed culture
      collection and analysis of antibiograms. Patients with febrile UTI (>38 degrees
      5) or recent history of urolithiasis were excluded. DISCUSSION: Fifty-seven
      patients underwent 111 5-day courses of antibiotics. The two main bacteria
      involved were Escherichia coli and Klebsiella Pneumoniae. Most commonly
      prescribed antibiotics were cephalosporins, cotrimoxazole, fluoroquinolones and
      nitrofurantoins. On day 4 of the antibiotic course, bacteria were eradicated in
      99% of cases. Clinical cure occurred in all patients by day 5 (end of treatment).
      After treatment, recurrence of UTI occurred in 16% of patients at week 3, 38% at
      week 6 and 50% at week 9. This rate was not significantly different from patients
      initially treated for aBact (20%, 35% and 44%, respectively). The UTI-free period
      was significantly shorter after treatment for aBact (45.5 days) than after
      treatment for UTI (53.7 days). None of the following characteristics were found
      to be risk factors for UTI: level or severity of lesion, gender, voiding mode,
      use of anticholinergic drugs and time since lesion. Results of this study support
      the use of a short 5-day course of antibiotics to treat mild UTI in patients with
      spinal cord injury, and provide further evidence against treatment of aBact.

PMID- 28503325
TI  - Ceftolozane/tazobactam for febrile UTI due to multidrug-resistant Pseudomonas
      aeruginosa in a patient with neurogenic bladder.
AB  - INTRODUCTION: Urinary tract infections (UTI) are a major public health problem
      among spinal cord injury (SCI) patients. They frequently involve multidrug
      resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic
      combination approved for complicated intra-abdominal and UTI caused by Gram
      positive and Gram-negative organisms, including some MDR strains. Little is known
      about the use of this agent for complicated febrile UTI occurring among SCI
      patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). CASE
      PRESENTATION: We describe the case of a 35-year-old man with SCI due to multiple
      sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and
      double J catheter, who developed a febrile UTI due to a MDR PSA, which was
      susceptible only to amikacin and colistin. Because of this MDR phenotype and the
      underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given
      as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin.
      Thanks to this treatment, the patient had a favorable outcome with no clinical
      signs of UTI or positive urine culture up to 1 month after diagnosis. DISCUSSION:
      C/T seems to be an effective and safe therapeutic option for febrile UTI due to
      MDR PSA in SCI patients with neurogenic bladder, even when administered in
      monotherapy for 10 days.

PMID- 28503326
TI  - Incomplete paraplegia caused by extramedullary hematopoiesis in a patient with
      thalassemia intermedia.
AB  - INTRODUCTION: Extramedullary hematopoiesis (EMH) is the production of blood cell
      precursors outside the bone marrow that occur in various hematological diseases.
      In patients with thalassemia intermedia, ineffective erythropoiesis drives
      compensatory EMH in the liver, pancreas, pleura, spleen, ribs and spine. CASE
      PRESENTATION: We describe a patient with thalassemia intermedia who presented
      with acute neurological symptoms caused by paraspinal EMH, which responded well
      to combination therapy of steroid, hypertransfusion, laminectomy and excision of
      pseudotumor and hydroxyurea therapy to boost the formation of fetal haemoglobin.
      DISCUSSION: Prompt recognition of EMH based on clinical presentation and typical
      radiological findings should be made. Early treatment is recommended to prevent
      irreversible damage to the spinal cord.

PMID- 28503327
TI  - The characteristics of traumatic spinal cord injuries at a referral hospital in
      Northern Tanzania.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: To describe the epidemiology of
      traumatic spinal cord injury (TSCI) in Northern Tanzania. SETTING: Main referral
      hospital for Northern Tanzania. METHODS: A retrospective review of 125 TSCI cases
      admitted to Kilimanjaro Christian Medical Centre (KCMC) over a period of 5 years.
      RESULTS: We included 125 patients in the sample size, with a male majority of 107
      (85.6%), giving a male-to-female ratio of 5.9:1. The mean age at injury was 39.9
      (+/-16.0) years. Overall, 66 (52.8%) were farmers and an overwhelming majority
      (109 (87.2%)) were referrals from peripheral medical centres. Fall injuries
      accounted for 65 (52.0%) of the admissions and 49 (39.2%) were injured due to a
      Road Traffic Accident (RTA). Severity of injury was classified according to the
      American Spinal Injury Association Impairment Scale (AIS) and 57 (45.6%) injuries
      were categorised as AIS A and 68 (54.4%) as AIS BCD. Cervical level injuries (59
      (47.2%)) were the most frequent among the cohort. The in-hospital mortality rate
      was 24.1%. CONCLUSION: The majority of patients affected by TSCIs were young
      males and the most common cause was fall injuries. Cervical level injuries were
      the most common and in-hospital mortality was high.

PMID- 28503329
TI  - Optical Fluorescence Microscopy for Spatially Characterizing Electron Transfer
      across a Solid-Liquid Interface on Heterogeneous Electrodes.
AB  - Heterogeneous catalytic materials and electrodes are used for (electro)chemical
      transformations, including those important for energy storage and utilization.1,
      2 Due to the heterogeneous nature of these materials, activity measurements with
      sufficient spatial resolution are needed to obtain structure/activity
      correlations across the different surface features (exposed facets, step edges,
      lattice defects, grain boundaries, etc.). These measurements will help lead to an
      understanding of the underlying reaction mechanisms and enable engineering of
      more active materials. Because (electro)catalytic surfaces restructure with
      changing environments,1 it is important to perform measurements in operando. Sub
      diffraction fluorescence microscopy is well suited for these requirements because
      it can operate in solution with resolution down to a few nm. We have applied sub
      diffraction fluorescence microscopy to a thin cell containing an electrocatalyst
      and a solution containing the redox sensitive dye p-aminophenyl fluorescein to
      characterize reaction at the solid-liquid interface. Our chosen dye switches
      between a nonfluorescent reduced state and a one-electron oxidized bright state,
      a process that occurs at the electrode surface. This scheme is used to
      investigate the activity differences on the surface of polycrystalline Pt, in
      particular to differentiate reactivity at grain faces and grain boundaries.
      Ultimately, this method will be extended to study other dye systems and electrode
      materials.

PMID- 28503328
TI  - Phrenic pacing compared with mechanical ventilation.
AB  - STUDY DESIGN: Comparable case series. OBJECTIVES: High-cervical spinal cord
      injury (SCI) may disrupt the ability to breathe sufficiently. To restore
      respiration a phrenic nerve pacer can be implanted. The aims of this study were
      to describe the use of phrenic nerve pacing in tetraplegics in Denmark and
      compare the users with a population of ventilator dependent tetraplegics.
      SETTING: Clinics for Spinal Cord Injuries, and Respiratory Centre East,
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. METHODS: Nine
      tetraplegic individuals who had implantation of a phrenic nerve pacer and 16 home
      mechanical ventilator dependent tetraplegics met the inclusion criteria. Data
      were retrieved from medical records and a structured follow-up interview with
      seven individuals from each group. RESULTS: No significant differences were found
      when comparing age at injury, time since injury, length of hospitalization,
      incidence of pneumonia, number of pneumonia hospitalizations, number of tracheal
      suctions, speech quality and activities of daily living or quality of life. On
      the Short Form Health Survey (SF36) mental health summary the median for both
      users of phrenic nerve pacing and users of mechanical ventilation was one s.d.
      above the mean of a standard population. CONCLUSIONS: Nine people have had a
      phrenic nerve pacer implanted. They do not significantly differ from a group of
      home mechanical ventilator dependent tetraplegics on a number of performance
      measures, but both groups seem to have better quality of life than a standard
      population.

PMID- 28503330
TI  - Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in
      Streptozotocin-Induced Diabetic Rats.
AB  - Aim. In this study, we aimed to investigate the effects of febuxostat, a novel
      inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-)
      induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal
      injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as
      controls. The control and diabetic rats were treated with and without febuxostat
      for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected
      every 4 weeks. Rat livers were extracted for detecting gene expression, content,
      and bioactivity of XO. Results. Diabetic rats showed significantly increased
      serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels.
      Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were
      also significantly increased in these rats. In diabetic rats, at week 8,
      febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr
      and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN
      levels decreased by >30% in these rats. Although hepatic gene expression,
      content, and activity of XO increased significantly in diabetic rats, febuxostat
      only slightly decreased its content. Conclusions. Febuxostat significantly
      attenuated renal damage in STZ-induced diabetic rats in addition to exerting
      hypouricemic effect.

PMID- 28503332
TI  - Chronic Neuropsychological Sequelae in a Patient with Nontumorous Anti-NMDA
      Receptor Encephalitis.
AB  - Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune
      disorder tightly conceptualized only as recently as the mid-2000s. It presents
      itself in a combination of psychiatric, neurological, and autonomic features. We
      observe a unique case with probable earlier episode (prior to the mid-2000s
      conceptualization of the disease) and a later relapse, accompanying a
      comprehensive neuropsychological profile tracked after the relapse and subsequent
      improvement. Neurocognitive findings revealed residual frontal deficits with mood
      changes even in the state after plasmapheresis. This case is the first to
      describe posttreatment cognition in anti-NMDAR encephalitis after probable serial
      autoimmune episodes.

PMID- 28503333
TI  - Peritoneal Keratin Granulomatosis Associated with Endometrioid Adenocarcinoma of
      the Uterine Corpus in a Woman with Polycystic Ovaries: A Potential Pitfall-A Case
      Report and Review of the Literature.
AB  - Peritoneal keratin granulomatosis is a rare condition included under
      granulomatous lesions of the peritoneum. It can be secondary to neoplasms of the
      female genital tract and can mimic carcinomatosis intraoperatively. A case of a
      40-year-old woman with a history of polycystic ovaries and a chief complaint of
      vaginal bleeding is presented. She was diagnosed with endometrioid adenocarcinoma
      with squamous differentiation in endometrial curettings. Intraoperatively, many
      peritoneal nodules were found, interpreted as peritoneal carcinomatosis. The
      woman underwent a total abdominal hysterectomy with bilateral salpingo
      oophorectomy, omentectomy, bilateral pelvic lymphadenectomy, and appendicectomy.
      Multiple biopsies were taken, as well as peritoneal washings. Microscopic
      examination revealed multiple keratin granulomas on the serosal surface of the
      ovaries, fallopian tubes, appendix, and omentum. Lymph node metastasis was not
      found. Peritoneal keratin granulomas (PKGs) have been reported in cases of
      endometrioid adenocarcinoma with squamous differentiation of the uterine corpus,
      ovary, and atypical adenomyoma. It should be noted that the prognosis of cases of
      peritoneal keratin granulomas without viable tumor cells is favourable and that
      the histologic examination is essential for its diagnosis. We report a case of
      PKG in a patient with endometrial carcinoma with squamous differentiation, being
      the first in a woman with polycystic ovaries.

PMID- 28503334
TI  - Retained Surgical Drains in Orthopedics: Two Case Reports and a Review of the
      Literature.
AB  - Though a relatively rare event, retained surgical drains are preventable and can
      lead to significant consequences. Two case reports from our institution are
      discussed as examples for the challenging management of this problem as well as
      an overview of techniques for the prevention and removal of retained drains based
      on the current literature.

PMID- 28503331
TI  - Exercise Modality Is Differentially Associated with Neurocognition in Older
      Adults.
AB  - This study explored the effects of exercise modality and type of fitness index on
      cognitive function in the older adults as assessed via behavioral and
      neuroelectrical approaches. Sixty older adults were assigned to an aerobic
      exercise, a coordination exercise, or a control group based on their previous
      exercise experience. The participants completed congruent and incongruent trials
      of a modified Stroop Test, during which, event-related potentials were recorded.
      The participants also completed multiple physical tests that assessed health- and
      skill-related fitness. Our findings suggest that, in general, both aerobic and
      coordination exercise, as well as higher scores on health- and skill-related
      fitness indices, are positively associated with better performance of various
      cognitive functions in the elderly population. The mechanisms underlying these
      relationships may be differentially related to specific neuroelectrical processes
      involved in neurocognitive control.

PMID- 28503335
TI  - Primary Villoglandular Mucinous Adenocarcinoma of the Vulva.
AB  - Primary villoglandular mucinous adenocarcinoma of the vulva is rare tumor. We
      report a case of 68-year-old woman who developed this very uncommon malignant
      tumor. Immunohistochemical examination of this tumor revealed positive staining
      for Cytokeratin 20, Mucin 2, and CDX2, although Cytokeratin 7 and Mucin 6 were
      negative. This positive staining indicated the tumor enteric type characters. In
      order to exclude the possibility of the metastasis from another site, we
      thoroughly evaluated clinical data and extensively investigated the whole body.
      However, we could not detect any other tumors. The patient was treated by tumor
      resection. The patient remains free of disease 5 years after surgery.

PMID- 28503336
TI  - Plasmacytoma as a Mimicker of Colonic Carcinoma in an Elderly Man.
AB  - Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells.
      Although it is usually restricted to the bone marrow, extraskeletal spread in the
      form of localised extramedullary collections of malignant plasma cells
      (plasmacytomas) can occur. However, gastrointestinal tract involvement in
      multiple myeloma is rare and overt gastrointestinal bleeding from plasmacytoma is
      uncommon. We report a case of colonic plasmacytoma which presented with bleeding
      per rectum and was initially misdiagnosed as colonic neuroendocrine carcinoma.
      Later the patient presented with recurrence of the colonic mass along with
      multiple lytic bone lesions. The diagnosis of colonic plasmacytoma with
      progression into multiple myeloma was given. We also discuss here the diagnostic
      difficulty of plasma cell neoplasms in small biopsies of the colon.

PMID- 28503337
TI  - Complete Ectopia Cordis: A Case Report and Literature Review.
AB  - Ectopia cordis is a congenital heart exposure defined as complete or partial
      protrusion of heart through ventral defect in the thoracoabdominal wall alone or
      with other viscera in cases of pentalogy of Cantrell. This condition was first
      described by Haller et al. in 1706; since then many advances have been made.
      Diagnosis of ectopia cordis is done prenatally in well-equipped health facility
      by antenatal ultrasound scan so that early diagnosis and management plan can be
      initiated. The index case was delivered to uneducated rural family and admitted
      at 3 days of life and survived for seven days, even though most literatures state
      that majority died within four days even with surgery. So, in view of this, we
      presented this case report to deliberately draw the attention of
      paediatrician/obstetrician to the fact that even though this condition is rare,
      proactive search and diagnosis should be made and early treatment should be
      instituted, so that such a child may be salvaged.

PMID- 28503339
TI  - Restoration and Management of Healthy Wetland Ecosystems.

PMID- 28503338
TI  - Infrarenal Infected Aortic Aneurysm Caused by Streptococcus pyogenes.
AB  - Infectious aneurysm is a rare entity associated with significant morbidity and
      mortality. Current knowledge on pathogenesis, outcome, diagnosis, management, and
      follow-up remains debatable. We report the case of a patient with Streptococcus
      pyogenes aneurysm who was successfully treated with a homograft implant and
      discuss microbiological characteristics, diagnostic methods, and treatment
      options currently available for this serious disease.

PMID- 28503341
TI  - Peripheral and Central Nervous System Involvement in Recently Diagnosed Cases of
      Hypothyroidism: An Electrophysiological Study.
AB  - BACKGROUND: Hypothyroidism, one of the most common endocrine disorders, may
      induce neurological abnormalities at an early stage of the disease. AIM: The
      study was designed to assess the electrophysiological alterations of some
      selected variables of nerve conduction, brainstem auditory evoked potentials
      (BAEPs), and visual evoked potentials (VEPs) in hypothyroid patients. SUBJECTS
      AND METHODS: Sixty patients of newly diagnosed hypothyroidism and an equal number
      of age-matched controls were selected for the study. Nerve conduction studies
      that included parameters as latencies, conduction velocities, and amplitude of
      motor nerves, i.e., median, ulnar, common peroneal, tibial nerve, and sensory
      nerves, i.e., median and sural nerves was performed in both hypothyroid patients
      and controls. Further, BAEPs and VEPs of all the patients were done. The data
      were compiled and statistically analyzed using Student's unpaired t-test to
      observe any electrophysiological alterations in hypothyroid patients as compared
      to healthy controls. RESULTS: On comparative evaluation, statistically
      significant increase in latency of median, ulnar, tibial, and sural nerves;
      decrease in conduction velocities of all the tested nerves and decrease in
      amplitude of median, tibial, and sural nerves was observed in hypothyroid
      patients. Statistically significant increase in latencies, interpeak latencies,
      and decrease in amplitudes of BAEP waves and statistically significant increase
      in P100 latency of VEP was seen in hypothyroid patients. CONCLUSION: The results
      of our study suggest that peripheral and central neuropathy develops in patients
      of hypothyroidism at an early stage of disease and the electrophysiological
      investigations of such patients can help in timely detection and treatment of
      neurological disorders that occur due to thyroid hormone deficiency.

PMID- 28503340
TI  - Administration frequency as well as dosage of PTH are associated with development
      of cortical porosity in ovariectomized rats.
AB  - To investigate whether the administration frequency of parathyroid hormone (PTH)
      is associated with the development of cortical porosity, this study established
      15 dosage regimens of teriparatide [human PTH(1-34), TPTD] with four distinct
      concentrations and four distinct administration frequencies of TPTD to 16-week
      old ovariectomized rats. Our analyses demonstrated that the bone mineral density,
      mechanical properties, and bone turnover were associated with the total amount of
      TPTD administered. Our observations further revealed that the cortical porosity
      was markedly developed as a result of an increased administration frequency with
      a lower concentration of total TPTD administration in our setting, although the
      highest concentration also induced cortical porosity. Deconvolution fluorescence
      tiling imaging on calcein-labeled undecalcified bone sections also demonstrated
      the development of cortical porosity to be closely associated with the bone site
      where periosteal bone formation took place. This site-specific cortical porosity
      involved intracortical bone resorption and an increased number and proximity of
      osteocytic lacunae, occasionally causing fused lacunae. Taken together, these
      findings suggested the involvement of local distinctions in the rate of bone
      growth that may be related to the site-specific mechanical properties in the
      development of cortical porosity induced by frequent and/or high doses of TPTD.

PMID- 28503342
TI  - Phenotypic Detection and Antibiogram of beta-lactamase-producing Proteus Species
      in a Tertiary Care Hospital, India.
AB  - BACKGROUND: Proteus species cause a variety of community- and hospital-acquired
      illnesses. Synthesis of beta-lactamases is the predominant mechanism for
      resistance to beta-lactam antibiotics. Among the beta-lactamases, extended
      spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases are the most common.
      AIM: The objective of this study was to determine the occurrence of ESBL and AmpC
      beta-lactamases in Proteus species among various clinical isolates at a tertiary
      care hospital, India. MATERIALS AND METHODS: This study was done to identify
      various species of Proteus from clinical samples (n = 3922). Antimicrobial
      susceptibility was performed by Kirby-Bauer disc diffusion method. ESBL
      production was detected by modified double-disc synergy test and indirect
      modified three-dimensional tests and AmpC beta-lactamase production by AmpC disc
      test and modified Hodge test. RESULTS: Proteus species were isolated in 5.4%
      (101/1876) specimens. Three Proteus species isolated were Proteus mirabilis 62.4%
      (63/101), Proteus vulgaris 29.7% (30/101), and Proteus penneri 7.9% (8/101). ESBL
      producers confirmed by both tests were of 88.1% (89/101). Only AmpC beta
      lactamase was produced by four isolates. Coproduction of ESBL and AmpC beta
      lactamase was observed in 58.4% (52/89) of isolates. Twelve isolates were non
      beta-lactamase producers. Multidrug resistance (MDR) was found in 95.1% (96/101)
      of isolates, 50.5% (51/101) were possibly extensively drug resistant and none
      were pan drug resistant. None of the isolates were resistant to piperacillin
      tazobactam. P. penneri isolates exhibited high resistance to most of the
      antibiotics. CONCLUSIONS: A high prevalence of ESBL and AmpC beta-lactamases was
      found that concurrently showed MDR. Phenotypic methods for the detection of beta
      lactamases are easy and simple and can be implemented in routine diagnostic
      laboratories along with susceptibility testing. These data will assist the
      clinicians in the management and control of infections.

PMID- 28503343
TI  - Evaluation of Serum and Urinary Neopterin Levels as a Biomarker for Occupational
      Exposure to Crystalline Silica.
AB  - BACKGROUND: Crystalline silica is a commonly used mineral in various industries
      and construction activities, and it is so important introducing potential
      biomarkers to identify early indicators of biological effects in its high-risk
      occupational exposures. AIM: The present study was aimed to assess the blood and
      urinary neopterin as an early biomarker of exposure in the workers of an
      insulator manufacturing plant who are exposed to crystalline silica. SUBJECTS AND
      METHODS: This analytical descriptive study was done among two groups of exposed
      workers (n = 55) and unexposed office workers (n = 38) of an insulator
      manufacturing plant. Statistical software R was used to determine sample size and
      select the participants by random sampling among nonsmoker workers. Sampling of
      airborne silica in breathing zone of participants was done based on the National
      Institute for Occupational Safety and Health method 7601. The urinary and blood
      samples were collected and prepared for analysis by high-performance liquid
      chromatography to determine the level of urinary and serum neopterin. All of the
      statistical analyses were carried out using SPSS 22. RESULTS: The airborne silica
      concentration was significantly different between two exposed and unexposed
      groups (P < 0.001, 0.27 [0.11] vs. 0.0028 [0.0006] mg/m3, respectively). The
      urinary neopterin in exposed group is significantly higher than the unexposed one
      (P < 0.001, 97.67 [30.24] vs. 55.52 [2.18] MUmol/mol creatinine, respectively).
      Neopterin level of serum in exposed group is higher than the unexposed group, and
      there is a significant difference between them (P < 0.001, 6.90 [2.70] vs. 2.20
      [1.20] nmol/l, respectively). The positive significant correlations were found
      between silica exposure concentration with urinary and serum neopterin (P <
      0.001, r = 0.36 and 0.59, respectively). CONCLUSIONS: Considering the sensitively
      and easily measurement of neopterin in biological fluid and also the
      statistically significant positive relationships which were found between the
      airborne silica concentration and neopterin levels in the present study, the
      serum and urinary neopterin levels can be considered the potential biomarkers of
      silica exposure for doing further comprehensive studies in this area.

PMID- 28503344
TI  - Adnexal Tumors of Skin: An Experience at a Tertiary Care Center at Delhi.
AB  - BACKGROUND: Adnexal skin tumors are a heterogeneous group of uncommon tumors
      usually misdiagnosed clinically due to a huge variety of types and their
      variants. Histopathology usually helps in establishing the diagnosis. AIMS: The
      study was undertaken to analyze the morphological, clinical, and histological
      features of adnexal tumors (ATs) of the skin at our center over a period of 4
      years. SUBJECTS AND METHODS: retrospective study was conducted over a period of 4
      years (April 2010-March 2014), comprising 25 ATs of skin diagnosed in the
      Department of Pathology, Hamdard Institute of Medical Sciences and Research,
      Jamia Hamdard, New Delhi. All the consecutively reported AT cases were reviewed
      and reclassified as AT arising from sebaceous glands, hair follicles, or sweat
      glands. The concordance of clinical and histopathological diagnosis was also
      assessed. RESULTS: Most of the ATs were benign (24/25) with head and neck being
      the most common location (72%). Nearly 56% of the tumors exhibited sweat gland
      differentiation, 28% hair follicle differentiation, and sebaceous gland tumors
      accounted for 16%. The most common varieties of tumors encountered in the present
      study included hidradenoma papilliferum and pilomatricoma. The concordance
      between clinical and histopathological diagnosis was found to be 50%
      approximately. CONCLUSIONS: ATs of the skin are rare neoplasms with benign tumors
      being far more common. They are often misdiagnosed clinically, so histopathology
      remains the gold standard for establishing an accurate diagnosis of skin ATs.

PMID- 28503345
TI  - Awareness and Attitudes toward Organ Donation in Rural Puducherry, India.
AB  - BACKGROUND: For many of the end-stage organ diseases, organ transplantation is
      the most preferred treatment. The need for the organ transplantation is higher
      than the availability. For the transplantation program to be successful,
      awareness regarding organ donation is needed and people must have a positive
      attitude toward donating organs. AIM: This study aims to assess the awareness and
      attitudes regarding organ donation among the rural population and to evaluate the
      sociodemographic factors associated with their awareness. SUBJECTS AND METHODS:
      This community-based cross-sectional study was conducted among 360 people living
      in 4 villages of Puducherry. Face-to-face interviews were carried out using
      pretested questionnaire, which included the sociodemographic data. Data were
      entered into Excel and analyzed using Statistical Package for Social Sciences.
      RESULTS: Of 360 participants, 88% (317/360) were aware of organ donation. Among
      these 317 participants, awareness was highest in the age group 18-30 years 98.8%
      (87/88), male 91% (147/161), higher secondary and above 100% (58/58), and Class 1
      socioeconomic status 92% (13/14). Source of awareness about organ donation was
      primarily through media 83% (263/317). The majority of the participants 88%
      (281/317) felt that the purpose of organ donation was to save life. Most of the
      participants 91% (290/317) said that all healthy adults are eligible organ donors
      and 87% (275/317) of the participants said that monetary benefits could not be
      accepted for organ donation. Most of the participants 70% (223/317) were willing
      to donate their organs after death. Among the participants who refused to donate
      their organs, family refusal 57% (25/44) was the most common reason. CONCLUSION:
      This study shows that there is a high level of awareness about organ donation
      among rural people and most of the participants are willing to donate their
      organs.

PMID- 28503346
TI  - Color Stability of Heat-cure Acrylic Resin Subjected to Simulated Short-term
      Immersion in Fast-acting Denture Cleansers.
AB  - BACKGROUND: Regular usage of denture cleansers is recommended in complete denture
      wearers for effective plaque control, and these cleansers alter the physical
      properties of acrylic resin over a period of time. Thus, an in vitro study was
      carried out to assess the effect of denture cleansers on the color stability of
      heat-cure denture base resin. AIM: The aim of the present study was to evaluate
      the effect of commercially available fast-acting denture cleansers on the color
      stability of heat-cure denture base resin at different time intervals. MATERIALS
      AND METHODS: Thirty-six heat-cure acrylic resin (Ivoclar Triplex Hot-V) specimens
      are randomly allocated into four groups - Group A (distilled water as control);
      Group B (polident - 3 min); Group C (fixodent scope plus); and Group D (stain
      away plus) comprising of nine samples each. After recording the baseline values,
      the specimens were immersed in their respective cleansing solutions for a
      prescribed time interval. This procedure was repeated daily, and the color change
      (DeltaE) was evaluated after 90 and 180 days interval using a colorimeter in a
      standard "Commission International de l'Eclairage" color system. STATISTICAL
      ANALYSIS USED: Paired t-test and Dunnett's T3 test. RESULTS: All the groups
      exhibited a variable color change (DeltaE) for an immersion period of 90 days.
      However, significant color differences (P = 0.001) were noticed among the test
      groups after 180 days. CONCLUSION: The color change of denture base resin was
      greater for Group D followed by Groups B, C, and A respectively after 180 days of
      immersion. The DeltaE values of all test groups increased with time.

PMID- 28503347
TI  - Wasting of Extensor Digitorum Brevis as a Decisive Preoperative Clinical
      Indicator of Lumbar Canal Stenosis: A Single-center Prospective Cohort Study.
AB  - BACKGROUND: The dilemma in managing patients with low back ache lies in
      differentiating radiculopathy from lumbar canal stenosis. This has a huge bearing
      in patients being planned for surgical intervention as underperforming leads to
      failed back syndrome whereas over-doing leads to instability. There still remains
      a loophole in clinically diagnosing lumbar canal stenosis. AIM: We opt to utilize
      a simple bedside clinical examination in routinely assessing patients presenting
      with low back ache in ruling out underlying canal stenosis. SUBJECTS AND METHODS:
      We performed a prospective study on 120 consecutive patients presenting with low
      back ache in the spine clinic. Each of them was neurologically examined and
      thoroughly assessed for wasting of extensor digitorum brevis (EDB) muscles. These
      were then correlated with the radio-imaging and the intraoperative findings.
      RESULTS: Lumbar canal stenosis was mostly observed in the age group of 50-60
      years. Diagnosis for L3/4 canal stenosis was made in 44/120 (36.6%), L5-S1 in
      52/120 (43.3%), and L3/L4/L5 level in 48/120 (40%) of patients. EDB wasting was
      seen unilaterally in 72/120 (60%) and bilaterally in 36/120 (30%) of the study
      group. CONCLUSION: This study appraises the clinical implication of observing for
      the wasting of EDB muscle so as to aid in the diagnosis of lumbar canal stenosis.
      This simple bedside clinical pearl can help us in predicting the need of further
      imaging studies and also in taking right therapeutic decision.

PMID- 28503348
TI  - Emerging Trends in the Epidemiological Pattern of Head and Neck Cancers in Lagos,
      Nigeria.
AB  - BACKGROUND: Unfortunately, despite an increase in medical knowledge, survival
      rates of head and neck cancers (HNCs) have not been observed to improve greatly.
      This is true, especially in tumors located in obscure primary sites or late
      presentation. AIM: The purpose of this study is to assess the epidemiologic
      pattern of HNCs and to evaluate its emerging trends and patterns in Lagos state.
      SUBJECTS AND METHODS: A retrospective study was conducted from 2003 to 2013 that
      analyzed histologically diagnosed cases of HNC at the Pathology Departments of
      the two tertiary teaching hospitals in Lagos. Data analysis was performed using
      the Statistical Package for the Social Sciences (version 20) statistical
      software. RESULTS: One thousand and eighty-three cases of head and neck
      malignancies were recorded. A female: male ratio of 1.01:1 was reported with mean
      age of 39.6 (standard deviation 21.1) years. The oral cavity was the most
      affected anatomic site (21.2%, 230/1083) in the period under review. Malignant
      epithelial tumors accounted for 72% (779/1083) of cases seen. Carcinomas were the
      most common histological variant seen (67%, 726/1083) and squamous cell carcinoma
      accounted for 58% (421/726) of carcinomas recorded. Oral cavity malignancies
      (21.8%, 118/540) were the most common in males while thyroid malignancies (28.5%,
      155/543) were the most seen in females. In children (<=15 years), the most common
      histologic findings were carcinomas (42.3%; 77/182) and retinoblastomas (23.6%;
      43/182). CONCLUSION: Epithelial malignancies were the most common malignancy in
      the study, and the oral cavity appears to be the increasingly predominant site
      for HNCs. A changing pattern in gender predominance, age distribution, and
      frequency with histological variants and anatomical sites was also observed in
      this study.

PMID- 28503349
TI  - Medial Malleolar Fractures: An Anatomic Survey Determining the Ideal Screw
      Length.
AB  - BACKGROUND: Medial malleolar fractures are frequent, and their treatment is
      familiar to the orthopedic surgeon. Lag screw fixation using partially threaded
      screws remains the standard treatment method for medial malleolar fractures.
      However, the literature lacks a defined method for selecting lag screw length,
      relying more so on the empiric choice of the surgeon. AIM: The aim of this study
      is to help define the ideal lag screw length for medial melleolar fracture
      fixation. MATERIALS AND METHODS: One hundred and sixteen anatomic specimens were
      included in the study. A transverse cut was performed in the distal third of the
      tibia, roughly 1 and a half times the distal tibial plafond width from the ankle
      joint. A coronal cut was then performed using the center of the medial malleolus.
      Three observers measured the distance between the medial malleolus tip and
      beginning of the medullary canal in all anatomic specimens. Differences in
      measurements were statistically compared, level of (P <= 0.05). Interclass
      correlation coefficient (ICC) significance level was set at P < 0.05. RESULTS:
      Measurement average was 55 mm between the medial malleolus tip and the medullary
      canal, with a standard deviation of 10 mm. High concordance (ICC: 0.819) was
      achieved among all pairs of observers (P < 0.01). The systematic difference among
      measurements was absent, and random distribution around general measurements was
      observed. CONCLUSION: The authors recommend a screw length of no more than 45 mm
      to optimize the location of the screw threads in the best cancellous bone in an
      effort to obtain the most compression.

PMID- 28503350
TI  - Clinicoradiologic Profile of Involvement and Healing in Tuberculosis of the
      Spine.
AB  - BACKGROUND: There is no much information about how tuberculous lesions of the
      spine progress/heal; what clinical and radiological features suggest
      progression/healing; what is the optimal duration of antitubercular treatment;
      and what clinical, laboratory, and radiological investigations and their
      frequency should be done to monitor the disease course. AIMS: The present study
      aimed to evaluate what specific clinicoradiologic features suggest involvement
      and healing in tuberculosis of the spine. SUBJECTS AND METHODS: Fifty spinal
      tuberculosis patients (30 males and 20 females) diagnosed clinicoradiologically
      were enrolled in the study. Patients were evaluated clinically, radiographically,
      and by magnetic resonance imaging (MRI) at regular intervals to monitor the
      disease course till 24 months of the initial presentation. RESULTS:
      Wedge/collapse (23/50 cases), soft tissue mass (29/50 cases), disc narrowing
      (45/54 discs), and endplate erosions (89/107 endplates) were the plain
      radiological findings of tubercular spinal involvement. Earliest sign of healing
      on plain radiography was decrease in fuzziness of endplate, ultimately leading to
      either sclerosis of endplate or fusion of adjacent vertebrae. Initial MRI
      findings included bone marrow edema (50/50 cases), discitis (53/62 discs),
      endplate erosions (105/123 endplates), pre- and para-vertebral collections (45/50
      cases), epidural involvement (26/50 cases), epidural spread (77/109 vertebrae),
      and subligamentous spread (42/50 cases). Earliest feature of healing on magnetic
      resonance (MR) examination was decrease in inflammatory soft-tissue masses and
      reduction in marrow edema. CONCLUSIONS: Salient features of spinal involvement in
      tuberculosis on plain radiograph were paradiscal involvement, endplate
      destruction, and soft tissue masses. Marrow edema, paravertebral collections,
      subligamentous spread, extradural component, endplate erosion, and discitis
      suggested tubercular involvement of the spine on MRI. A decrease in these was
      observed to have prognostic value both in monitoring disease course and response
      to chemotherapy. Based on the clinicoradiologic findings of the present study, we
      propose decision-making algorithm, follow-up algorithm, and MR examination
      protocol for spinal tuberculosis. LEVEL OF EVIDENCE: This was a Level II study.

PMID- 28503351
TI  - Subtrochanteric and Distal Femur Fractures in a Patient with Femoral Shaft
      Fracture Malunion and Knee Disarticulation: A Rare and Challenging Case Report.
AB  - This study aims to describe a rare and challenging case of a patient who
      presented ipsilateral subtrochanteric and distal femur fractures due to low
      energy trauma. The peculiarity of this case is the presence of femoral shaft
      fracture malunion and knee disarticulation in the same limb resulting from an
      accident suffered 30 years ago. The patient underwent femoral diaphyseal
      osteotomy and fixation of the subtrochanteric and distal femur fractures with a
      long cephalomedullary nail and distal femur locking plate, respectively. Despite
      the magnitude of the surgical procedure, all fractures healed, preserving the
      femoral length with the absence of infection and clinical complications. There
      was an improvement of the preinjury function attributed to the osteotomy of the
      femoral diaphyseal, which alleviated the anterior thigh discomfort.

PMID- 28503352
TI  - Serum Adiponectin Levels are Associated with Microcirculatory Function, but not
      with Coronary Artery Disease in the Young.

PMID- 28503353
TI  - A Systematic Review of Reproductive Coercion in International Settings.
AB  - Reproductive coercion is behavior that interferes with a woman's autonomous
      reproductive decision-making. It may take the form of birth control sabotage,
      pregnancy coercion, or controlling the outcome of a pregnancy. Perpetrators may
      be partners, a partner's family, or the woman's family. This article reviews the
      literature on reproductive coercion in international settings. In this review of
      10 research studies, findings are presented on prevalence and type of
      reproductive coercion, associated factors, specific tactics, relationship with
      intimate partner violence and domestic violence (in-laws particularly), and
      implications for women's reproductive health. Findings highlight reproductive
      coercion as a subset of intimate partner violence that is poorly understood,
      especially in international settings. More research is needed on protective
      factors, how interventions can capitalize on protective factors, and the
      strategies women use to resist reproductive coercion. Policy implications and
      recommendations are discussed with particular attention to issues related to
      diverse social and cultural environments.

PMID- 28503354
TI  - Mechanism of the P450-Catalyzed Oxidative Cyclization in the Biosynthesis of
      Griseofulvin.
AB  - Griseofulvin is an anti-fungal agent which has recently been determined to have
      potential anti-viral and anti-cancer applications. The role of specific enzymes
      involved in the biosynthesis of this natural product has previously been
      determined, but the mechanism by which a p450, GsfF, catalyzes the key oxidative
      cyclization of griseophenone B remains unknown. Using density functional theory
      (DFT), we have determined the mechanism of this oxidation that forms the oxa
      spiro core of griseofulvin. Computations show GsfF preferentially performs two
      sequential phenolic O-H abstractions rather than epoxidation to form an arene
      oxide intermediate. This conclusion is supported by experimental kinetic isotope
      effects.

PMID- 28503356
TI  - Towards an Obesity-Cancer Knowledge Base: Biomedical Entity Identification and
      Relation Detection.
AB  - Obesity is associated with increased risks of various types of cancer, as well as
      a wide range of other chronic diseases. On the other hand, access to health
      information activates patient participation, and improve their health outcomes.
      However, existing online information on obesity and its relationship to cancer is
      heterogeneous ranging from pre-clinical models and case studies to mere
      hypothesis-based scientific arguments. A formal knowledge representation (i.e., a
      semantic knowledge base) would help better organizing and delivering quality
      health information related to obesity and cancer that consumers need.
      Nevertheless, current ontologies describing obesity, cancer and related entities
      are not designed to guide automatic knowledge base construction from
      heterogeneous information sources. Thus, in this paper, we present methods for
      named-entity recognition (NER) to extract biomedical entities from scholarly
      articles and for detecting if two biomedical entities are related, with the long
      term goal of building a obesity-cancer knowledge base. We leverage both
      linguistic and statistical approaches in the NER task, which supersedes the state
      of-the-art results. Further, based on statistical features extracted from the
      sentences, our method for relation detection obtains an accuracy of 99.3% and a f
      measure of 0.993.

PMID- 28503357
TI  - How Bad Is It? Usefulness of the "7eed Model" for Scoring Severity and Level of
      Need in Complex Emergencies.
AB  - BACKGROUND: Humanitarian assistance is designated to save lives and alleviate
      suffering among people affected by disasters. In 2014, close to 25 billion USD
      was allocated to humanitarian assistance, more than 80% of it from governmental
      donors and EU institutions. Most of these funds are devoted to Complex
      Emergencies (CE). It is widely accepted that the needs of the affected population
      should be the main determinant for resource allocations of humanitarian funding.
      However, to date no common, systematic, and transparent system for needs-based
      allocations exists. In an earlier paper, an easy-to-use model, "the 7eed model",
      based on readily available indicators that distinguished between levels of
      severity among disaster-affected countries was presented. The aim of this paper
      is to assess the usefulness of the 7eed model in regards to 1) data availability,
      2) variations between CE effected countries and sensitivity to change over time,
      and 3) reliability in capturing severity and levels of need. METHOD: We applied
      the 7eed model to 25 countries with CE using data from 2013 to 2015. Data
      availability and indicator value variations were assessed using heat maps. To
      calculate a severity score and a needs score, we applied a standardised
      mathematical formula, based on the UTSTEIN template. We assessed the model for
      reliability on previous CEs with a "known" outcome in terms of excess mortality.
      RESULTS: Most of the required data was available for nearly all countries and
      indicators, and availability increased over time. The 7eed model was able to
      discriminate between levels of severity and needs among countries. Comparison
      with historical complex disasters showed a correlation between excess mortality
      and severity score. CONCLUSION: Our study indicates that the proposed 7eed model
      can serve as a useful tool for setting funding levels for humanitarian assistance
      according to measurable levels of need. The 7eed model provides national level
      information but does not take into account local variations or specific
      contextual factors.

PMID- 28503355
TI  - Stereoselective cis-Vinylcyclopropanation via a Gold(I)-Catalyzed Retro-Buchner
      Reaction under Mild Conditions.
AB  - A highly stereoselective gold(I)-catalyzed cis-vinylcyclopropanation of alkenes
      has been developed. Allylic gold carbenes, generated via a retro-Buchner reaction
      of 7-alkenyl-1,3,5-cycloheptatrienes, react with alkenes to form
      vinylcyclopropanes. The gold(I)-catalyzed retro-Buchner reaction of these
      substrates proceeds by simple heating at a temperature much lower than that
      required for the reaction of 7-aryl-1,3,5-cycloheptatrienes (75  degrees C vs 120
      degrees C). A newly developed Julia-Kocienski reagent enables the synthesis of
      the required cycloheptatriene derivatives in one step from readily available
      aldehydes or ketones. On the basis of mechanistic investigations, a
      stereochemical model for the cis selectivity was proposed. An unprecedented gold
      catalyzed isomerization of cis- to trans-cyclopropanes has also been discovered
      and studied by DFT calculations.

PMID- 28503358
TI  - Behavior Problems and Post-traumatic Stress Symptoms in Children Beginning
      School: A Comparison of Pre- and Post-Earthquake Groups.
AB  - INTRODUCTION: Literature reviews caution that estimating the effects of disasters
      on the behavior of children following a disaster is difficult without baseline
      information and few studies report the effects of earthquakes on young children.
      In addition the relationship between age at the time of disaster and
      consequential behavior problems have not been reported for young children who
      experience disaster-related stress during a developmentally sensitive period.
      METHODS: Behavior problems and symptoms of post-traumatic stress (PTS) were
      reported for two groups of children from nearby neighborhoods during their first
      term at school, using the Behavior Problem Index by teacher report, following
      approved informed consent procedures. Data on one group, "Pre-EQ" (N=297), was
      collected four years before the beginning of the earthquakes on children born
      2001-2002. Data on the second group, "Post-EQ" (N=212), was collected
      approximately three to four years after the beginning of the earthquakes on
      children born 2007-2009 and living in heavily damaged neighborhoods. The Post-EQ
      group had significantly more children from high socioeconomic neighborhoods but
      no other significant differences on main demographic characteristics. RESULTS:
      The mean behavior problem score was significantly higher in the Post-EQ group
      (Mean =6.11) as compared to the Pre-EQ group (Mean = 3.78). PTS symptoms were
      also significantly higher in the Post-EQ group (Mean =2.91) as compared to the
      Pre-EQ group (Mean=1.98) and more children had high PTS scores (20.9% v. 8.8%,
      OR= 2.73, 95%CI =1.57, 4.76). Model testing identified that a younger age at the
      time of exposure was the only significant predictor of high numbers of PTS
      symptoms in the Post-EQ group. Discussion: Rates of teacher-reported behavior
      problems in young children more than doubled following the Christchurch
      earthquakes. Younger children may be more vulnerable to the effects of
      earthquakes that occur during a developmentally sensitive period. Additional
      research is needed to consider the effects of age and duration of disaster
      effects to better understand the effects of disasters on children, their families
      and communities.

PMID- 28503359
TI  - Maintaining Maternal and Child Health Services During the Ebola Outbreak:
      Experience from Pujehun, Sierra Leone.
AB  - BACKGROUND: During the Ebola outbreak the overall confidence of the population in
      the national health system declined in Sierra Leone, with a reduction in the use
      of health services. The objective of this study is to provide information on
      understanding of how Ebola impacted maternal and child health services in Sierra
      Leone. Data come from an operational setting which is representative of the
      communities affected by the outbreak. METHODS: By integrating hospital registers
      and contact tracing form data with healthcare workers and local population
      interviews, the transmission chain was reconstructed. Data on the utilization of
      maternal and neonatal health services were collected from the local district's
      Health Management Information System. The main measures put in place to control
      the Ebola epidemic were: the organization of a rapid response to the crisis by
      the local health authorities; triage, contact tracing and quarantine; isolation,
      clinical management and safe burials; training and community sensitization.
      RESULTS: A total of 49 case patients were registered between July and November
      2014 in the Pujehun district. Hospitalization rate was 89%. Overall, 74.3% of
      transmission events occurred between members of the same family, 17.9% in the
      community and 7.7% in hospital. The mean number of contacts investigated per case
      raised from 11.5 in July to 25 in September 2014. The 2014 admission trend in the
      pediatric ward shows a decrease after beginning of June: the reduction was almost
      significant in the period July-December (p 0.05). The admission in the maternity
      ward showed no statistical differences in comparison with the previous year (p
      0.07). Also the number of deliveries appeared to be similar to the previous year,
      without significant variations (p 0.41). CONCLUSION: The Ebola outbreak reduced
      the number of patients at hospital level in Pujehun district. However, the
      activities undertaken to manage Ebola, reduced the spread of infection and the
      impact of the disease in mothers and children. A number of reasons which may
      explain these results are presented and discussed.

PMID- 28503360
TI  - Risk Criteria in Hospital Site Selection: A Systematic Review.
AB  - INTRODUCTION: Hospitals should be safe and remain functional in emergencies and
      disasters as it is mentioned in the Sendai Framework. Proper selection of a
      hospital location has a direct effect on survival of affected population in
      disasters as well as cost and benefit of the hospital in non-emergency situation.
      Different studies applied different criteria for Hospital Site Selection (HSS).
      The present study through a systematic review aimed to find out a categorized
      criteria list that have been used for (HSS) in the literature. METHODS: In
      accordance with the PRISMA statement, "PubMed", "ScienceDirect", "Google
      Scholar", and "Scopus" were searched up to end of 2015. All English Articles that
      were published in peer-reviewed journals and had discussed site selection
      criteria for hospitals were included. Out of 41 articles, 15 met the inclusion
      criteria in which 39 general criteria for HSS were applied. These criteria were
      categorized in six main groups including cost, demand, environmental,
      administrative, disaster risk, and "other" concerns through a focus group
      discussion. RESULTS: Accordingly, the application percentage of cost, demand,
      environmental, administrative, disaster risk, and "other" concerns in the
      articles was 100, 93.3, 53.3, 33.3, 20.0, and 13.3 respectively. The least
      devoted attention was to disaster risk issues. DISCUSSION: Few researchers
      applied risk related criteria for HSS. Further consideration of "risk of hazards"
      and "burden of diseases" in comprehensive studies, is recommended for HSS to
      guide the decision makers for building more resilient hospitals. Keywords  
      Hospital, Site selection, Systematic review, Disaster risk.

PMID- 28503361
TI  - A Review of the Key Considerations in Mental Health Services Research: A Focus on
      Low-Income Children and Families.
AB  - Children have been particularly vulnerable to the economic challenges of the past
      decade, with half (45 to 51%) of children under the age of 18 living in a low
      income home and nearly 22% of those living in poverty. Low-income children are
      overrepresented in a range of statistics on psychosocial maladjustment issues,
      but their families are less likely than other socioeconomic groups to participate
      in mental health services and intervention research. Thus, this review asserts
      that substantive advances in mental health services and intervention research
      with low income families must move beyond a between-group, deficit-focused
      perspective to a more nuanced contemplation of how to: 1) Operationalize the
      "income" in low-income families; 2) Disentangle the interrelationship of low
      income, race, and ethnicity; and 3) Optimize recruitment, engagement and
      retention efforts via sensitivity to the culture of low-income status. Examples
      of mental health services and intervention research with low-income families will
      be discussed, and a summary, conclusions, and directions for future research are
      discussed in the context of these recommendations.

PMID- 28503362
TI  - A Case of Myoclonus-Dystonia Responding to Low-frequency Pallidal Stimulation.
AB  - BACKGROUND: High-frequency pallidal stimulation has been shown to improve various
      types of dystonia, including myoclonus-dystonia. CASE REPORT: We report a case of
      epsilon sarcoglycan mutation-negative myoclonus-dystonia with response to low
      frequency bilateral pallidal stimulation. DISCUSSION: Low-frequency pallidal
      stimulation provides an effective means of treating various dystonias, regardless
      of genetic status, as in our case, as it provides increased programming options
      with fewer adverse effects.

PMID- 28503363
TI  - Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of
      Current Hurdles.
AB  - BACKGROUND: While there is no breakthrough progress in the medical treatment of
      essential tremor (ET), in the past decades several remarkable achievements
      happened in the surgical field, such as radiofrequency thalamotomy, thalamic deep
      brain stimulation, and gamma knife thalamotomy. The most recent advance in this
      area is magnetic resonance-guided focused ultrasound (MRgFUS). METHODS: The
      purpose of this review is to discuss the new developments and trials of MRgFUS in
      the treatment of ET and other tremor disorders. RESULTS: MRgFUS is an
      incisionless surgery performed without anesthesia and ionizing radiation (no risk
      of cumulative dose and delayed side effects). Studies have shown the safety and
      effectiveness of unilateral MRgFUS-thalamotomy in the treatment of ET. It has
      been successfully used in a few patients with Parkinson's disease-related tremor,
      and in fewer patients with fragile X-associated tremor/ataxia syndrome. The
      safety and long-term effects of the procedure are still unclear, as temporary and
      permanent adverse events have been reported as well as recurrence of tremor.
      DISCUSSION: MRgFUS is a promising new surgical approach with a number of unknowns
      and unsolved issues. It represents a valuable option particularly for patients
      who refused or could not be candidates for other procedures, deep brain
      stimulation in particular.

PMID- 28503364
TI  - Human as the Ultimate Wound Healing Model: Strategies for Studies Investigating
      the Dermal Lipidome.
AB  - PURPOSE OF REVIEW: Educate the reader of the multiple roles undertaken by the
      human epidermal lipidome and the experimental techniques of measuring them.
      RECENT FINDINGS: Damage to skin elicits a wound healing process that is capped by
      the recreation of the lipid barrier. In addition to barrier function, lipids also
      undertake an active signaling role during wound healing. Achievement of these
      multiple functions necessitates a significant complexity and diversity in the
      lipidome resulting in a composition that is unique to the human skin. As such,
      any attempts to delineate the function of the lipidome during the wound healing
      process in humans need to be addressed via studies undertaken in humans. SUMMARY:
      The human cutaneous lipidome is unique and play a functionally significant role
      in maintaining barrier and regulating wound healing. Modern mass spectrometry and
      Raman spectroscopy based methods enable the investigation epidermal lipidome with
      respect to those functions.

PMID- 28503365
TI  - Genetics, Diagnosis, and Monitoring of Pseudoexfoliation Glaucoma.
AB  - Recent studies have shed new light on the genetic factors underlying
      pseudoexfoliation syndrome, growing our understanding of the role of the lysyl
      oxidase-like 1 (LOXL1) gene and its various polymorphisms as well as identifying
      new genetic associations. Recent years have brought new insight on how these
      genetic factors interact with other factors, including environmental, to confer
      risk to individuals and populations worldwide. All of these findings may hold
      importance to the screening, diagnosis, and monitoring of pseudoexfoliation and
      may also help lead to the identification of novel therapeutic targets. This
      review serves as an update on the recent trends and findings in pseudoexfoliation
      syndrome.

PMID- 28503366
TI  - Is Trauma Memory Special? Trauma Narrative Fragmentation in PTSD: Effects of
      Treatment and Response.
AB  - Seminal theories posit that fragmented trauma memories are critical to
      posttraumatic stress disorder (PTSD; van der Kolk & Fisler, 1995; Brewin, 2014)
      and that elaboration of the trauma narrative is necessary for recovery (e.g.,
      Foa, Huppert, & Cahill, 2006). According to fragmentation theories, trauma
      narrative changes, particularly for those receiving trauma-focused treatment,
      should accompany symptom reduction. Trauma and control narratives in 77 men and
      women with chronic PTSD were examined pre- and post-treatment, comparing
      prolonged exposure (PE) and sertraline. Utilizing self-report, rater coding, and
      objective coding of narrative content, fragmentation was compared across
      narrative types (trauma, negative, positive) by treatment modality and response,
      controlling for potential confounds. Although sensory components increased with
      PE (d = 0.23 - 0.44), there were no consistent differences in fragmentation from
      pre- to post-treatment between PE and sertraline or treatment responders and non
      responders. Contrary to theories, changes in fragmentation may not be a crucial
      mechanism underlying PTSD therapeutic recovery.

PMID- 28503367
TI  - Etiology of Triarchic Psychopathy Dimensions in Chimpanzees (Pan troglodytes).
AB  - The current study undertook analyses of genealogical data from a sample of 178
      socially-housed chimpanzees (Pan troglodytes) with well-documented pedigrees, to
      clarify the etiologic bases of triarchic psychopathy dimensions and the influence
      of early social rearing experiences. Whereas biometric analyses for the full
      sample indicated significant heritability for the boldness dimension of
      psychopathy only, heritability estimates varied by early rearing, with all three
      triarchic dimensions showing significant heritabilities among mother-reared but
      not nursery-reared apes. For mother-reared apes, both genes and environment
      contributed to covariance between meanness and disinhibition, whereas environment
      contributed mainly to covariation between these dimensions and boldness. Results
      indicate contributions of both genes and environment to psychopathic tendencies,
      with an important role for early-rearing in their relative contributions to
      distinct phenotypic subdimensions. In conjunction with findings from human
      studies, results provide valuable insights into core biobehavioral processes
      relevant to psychological illness and health.

PMID- 28503369
TI  - Direct evidence of megamammal-carnivore interaction decoded from bone marks in
      historical fossil collections from the Pampean region.
AB  - Pleistocene South American megafauna has traditionally attracted the interest of
      scientists and the popular media alike. However, ecological interactions between
      the species that inhabited these ecosystems, such as predator-prey relationships
      or interspecific competition, are poorly known. To this regard, carnivore marks
      imprinted on the fossil bones of megamammal remains are very useful for
      deciphering biological activity and, hence, potential interspecific relationships
      among taxa. In this article, we study historical fossil collections housed in
      different European and Argentinean museums that were excavated during the 19th
      and early 20th centuries in the Pampean region, Argentina, in order to detect
      carnivore marks on bones of megamammals and provide crucial information on the
      ecological relationships between South American taxa during the Pleistocene. Our
      results indicate that the long bones of megafauna from the Pampean region (e.g.,
      the Mylodontidae and Toxodontidae families) exhibit carnivore marks. Furthermore,
      long bones of medium-sized species and indeterminate bones also present
      punctures, pits, scores and fractures. Members of the large-carnivore guild, such
      as ursids, canids and even felids, are recognised as the main agents that
      inflicted the marks. We hypothesize that the analysed carnivore marks represent
      the last stages of megaherbivore carcass exploitation, suggesting full
      consumption of these animals by the same or multiple taxa in a hunting and/or
      scavenging scenario. Moreover, our observations provide novel insights that help
      further our understanding of the palaeoecological relationships of these unique
      communities of megamammals.

PMID- 28503370
TI  - Cave features, seasonality and subterranean distribution of non-obligate cave
      dwellers.
AB  - Seasonality impacts species distributions through changes of the environmental
      conditions that affect the presence of individuals at a given place. Although the
      dynamics of cave microclimates are well known, only a few studies have evaluated
      the effects of such dynamics on non-strictly cave species. Here we assessed if
      species exploiting subterranean environments show changes in habitat occupation
      related to seasonal variation of cave microclimates. We surveyed 16 caves in
      central Italy every month for one year. Caves were subdivided into longitudinal
      sectors of three meters. In each sector we measured cave morphology and
      microclimatic features, assessed the occurrence of eight non-troglobitic taxa
      (orthopterans, spiders, gastropods and amphibians), and related species
      distribution to environmental features and sampling periods. The occurrence of
      most species was related to both cave morphology and microclimatic features. The
      survey month was the major factor determining the presence of species in cave
      sectors, indicating that cave-dwelling taxa show strong seasonality in activity
      and distribution. For multiple species, we detected interactions between sampling
      period and microclimatic features, suggesting that species may associate with
      different microhabitats throughout the year. The richest communities were found
      in sites with specific microclimates (i.e., high humidity, warm temperature and
      low light) but seasonality for species richness was strong as well, stressing the
      complexity of interactions between outdoor and subterranean environments.

PMID- 28503368
TI  - Running wheel training does not change neurogenesis levels or alter working
      memory tasks in adult rats.
AB  - BACKGROUND: Exercise can change cellular structure and connectivity (neurogenesis
      or synaptogenesis), causing alterations in both behavior and working memory. The
      aim of this study was to evaluate the effect of exercise on working memory and
      hippocampal neurogenesis in adult male Wistar rats using a T-maze test. METHODS:
      An experimental design with two groups was developed: the experimental group (n =
      12) was subject to a forced exercise program for five days, whereas the control
      group (n = 9) stayed in the home cage. Six to eight weeks after training, the
      rats' working memory was evaluated in a T-maze test and four choice days were
      analyzed, taking into account alternation as a working memory indicator.
      Hippocampal neurogenesis was evaluated by means of immunohistochemistry of BrdU
      positive cells. RESULTS: No differences between groups were found in the
      behavioral variables (alternation, preference index, time of response, time of
      trial or feeding), or in the levels of BrdU positive cells. DISCUSSION: Results
      suggest that although exercise may have effects on brain structure, a construct
      such as working memory may require more complex changes in networks or
      connections to demonstrate a change at behavioral level.

PMID- 28503371
TI  - Transcriptome sequencing and SNP detection in Phoebe chekiangensis.
AB  - BACKGROUND: Phoebe chekiangensis is a rare tree species that is only distributed
      in south-eastern China. Although this species is famous for its excellent wood
      properties, it has not been extensively studied at the molecular level. RESULTS:
      Here, the transcriptome of P. chekiangensis was sequenced using next-generation
      sequencing technology, and 75,647 transcripts with 48,011 unigenes were assembled
      and annotated. In addition, 162,938 putative single nucleotide polymorphisms
      (SNPs) were predicted and 25 were further validated using the Sanger method.
      CONCLUSION: The currently available SNP prediction software packages showed low
      levels of correspondence when compared. The transcriptome and SNPs will
      contribute to the exploration of P. chekiangensis genetic resources and the
      understanding of its molecular mechanisms.

PMID- 28503372
TI  - Endosymbiont interference and microbial diversity of the Pacific coast tick,
      Dermacentor occidentalis, in San Diego County, California.
AB  - The Pacific coast tick, Dermacentor occidentalis Marx, is found throughout
      California and can harbor agents that cause human diseases such as anaplasmosis,
      ehrlichiosis, tularemia, Rocky Mountain spotted fever and rickettsiosis 364D.
      Previous studies have demonstrated that nonpathogenic endosymbiotic bacteria can
      interfere with Rickettsia co-infections in other tick species. We hypothesized
      that within D. occidentalis ticks, interference may exist between different
      nonpathogenic endosymbiotic or nonendosymbiotic bacteria and Spotted Fever group
      Rickettsia (SFGR). Using PCR amplification and sequencing of the rompA gene and
      intergenic region we identified a cohort of SFGR-infected and non-infected D.
      occidentalis ticks collected from San Diego County. We then amplified a partial
      segment of the 16S rRNA gene and used next-generation sequencing to elucidate the
      microbiomes and levels of co-infection in the ticks. The SFGR R. philipii str.
      364D and R. rhipicephali were detected in 2.3% and 8.2% of the ticks,
      respectively, via rompA sequencing. Interestingly, next generation sequencing
      revealed an inverse relationship between the number of Francisella-like
      endosymbiont (FLE) 16S rRNA sequences and Rickettsia 16S rRNA sequences within
      individual ticks that is consistent with partial interference between FLE and
      SFGR infecting ticks. After excluding the Rickettsia and FLE endosymbionts from
      the analysis, there was a small but significant difference in microbial community
      diversity and a pattern of geographic isolation by distance between collection
      locales. In addition, male ticks had a greater diversity of bacteria than female
      ticks and ticks that weren't infected with SFGR had similar microbiomes to canine
      skin microbiomes. Although experimental studies are required for confirmation,
      our findings are consistent with the hypothesis that FLEs and, to a lesser
      extent, other bacteria, interfere with the ability of D. occidentalis to be
      infected with certain SFGR. The results also raise interesting possibilities
      about the effects of putative vertebrate hosts on the tick microbiome.

PMID- 28503373
TI  - Analysis of genomic variation in lung adenocarcinoma patients revealed the
      critical role of PI3K complex.
AB  - BACKGROUND: Molecularly targeted therapies improved survival status of some
      patients with lung adenocarcinoma, which accounts for 40% of all lung cancers,
      and in-depth study of gene alterations is important for the personalized
      treatment. METHODS: The legacy archive data of clinical information and genomic
      variations under the project TCGA Lung Adenocarcinoma were downloaded from the
      GDC Data Portal using R package TCGAbiolinks. The significantly aberrant copy
      number variants segments were figured out using GAIA. After annotation, the genes
      involving CNV were used to get enriched pathways. Recurrent amplifications and
      deletions were identified and visualized by OncoPrint. Genomic alterations in
      cancer, including CNV and mutations, were represented in Circos. RESULTS: The
      significantly aberrant CNV segments were found, and the genes involved were
      associated with the immune system. In an analysis of 517 mutation annotated
      files, we highlighted 63 highly recurrent mutated genes which were associated
      with lung cancer signaling. These genes involved in important pathways related to
      cancer progression. The intersections between the genes involving in the
      significantly aberrant CNV and the genes harboring recurrent somatic SNP were
      extracted. The PI3K protein family acted as critical roles in the lung
      adenocarcinoma, since the components of the PI3K protein family include PIK3C2B,
      PIK3CA, PIK3R1 and so forth were presented in the intersections. CONCLUSION: We
      represented a comprehensive annotation of genomic alterations in lung
      adenocarcinoma and proposed that PI3K signaling proteins were critical for it.

PMID- 28503374
TI  - Sooty tern (Onychoprion fuscatus) survival, oil spills, shrimp fisheries, and
      hurricanes.
AB  - Migratory seabirds face threats from climate change and a variety of
      anthropogenic disturbances. Although most seabird research has focused on the
      ecology of individuals at the colony, technological advances now allow
      researchers to track seabird movements at sea and during migration. We combined
      telemetry data on Onychoprion fuscatus (sooty terns) with a long-term capture
      mark-recapture dataset from the Dry Tortugas National Park to map the movements
      at sea for this species, calculate estimates of mortality, and investigate the
      impact of hurricanes on a migratory seabird. Included in the latter analysis is
      information on the locations of recovered bands from deceased individuals wrecked
      by tropical storms. We present the first known map of sooty tern migration in the
      Atlantic Ocean. Our results indicate that the birds had minor overlaps with areas
      affected by the major 2010 oil spill and a major shrimp fishery. Indices of
      hurricane strength and occurrence are positively correlated with annual mortality
      and indices of numbers of wrecked birds. As climate change may lead to an
      increase in severity and frequency of major hurricanes, this may pose a long-term
      problem for this colony.

PMID- 28503375
TI  - Network science meets respiratory medicine for OSAS phenotyping and severity
      prediction.
AB  - Obstructive sleep apnea syndrome (OSAS) is a common clinical condition. The way
      that OSAS risk factors associate and converge is not a random process. As such,
      defining OSAS phenotypes fosters personalized patient management and population
      screening. In this paper, we present a network-based observational, retrospective
      study on a cohort of 1,371 consecutive OSAS patients and 611 non-OSAS control
      patients in order to explore the risk factor associations and their correlation
      with OSAS comorbidities. To this end, we construct the Apnea Patients Network
      (APN) using patient compatibility relationships according to six objective
      parameters: age, gender, body mass index (BMI), blood pressure (BP), neck
      circumference (NC) and the Epworth sleepiness score (ESS). By running targeted
      network clustering algorithms, we identify eight patient phenotypes and
      corroborate them with the co-morbidity types. Also, by employing machine learning
      on the uncovered phenotypes, we derive a classification tree and introduce a
      computational framework which render the Sleep Apnea Syndrome Score (SASScore);
      our OSAS score is implemented as an easy-to-use, web-based computer program which
      requires less than one minute for processing one individual. Our evaluation,
      performed on a distinct validation database with 231 consecutive patients,
      reveals that OSAS prediction with SASScore has a significant specificity
      improvement (an increase of 234%) for only 8.2% sensitivity decrease in
      comparison with the state-of-the-art score STOP-BANG. The fact that SASScore has
      bigger specificity makes it appropriate for OSAS screening and risk prediction in
      big, general populations.

PMID- 28503377
TI  - Analysis of RecA-independent recombination events between short direct repeats
      related to a genomic island and to a plasmid in Escherichia coli K12.
AB  - RecA-independent recombination events between short direct repeats, leading to
      deletion of the intervening sequences, were found to occur in two genetic models
      in the Escherichia coli K12 background. The first model was a small E. coli
      genomic island which had been shown to be mobile in its strain of origin and,
      when cloned, also in the E. coli K12 context. However, it did not encode a site
      specific recombinase as mobile genomic islands usually do. It was then deduced
      that the host cells should provide the recombination function. This latter was
      searched for by means of a PCR approach to detect the island excision in E. coli
      K12 mutants affected in a number of recombination functions, including the 16 E.
      coli K12 site-specific recombinases, the RecET system, and multiple proteins that
      participate in the RecA-dependent pathways of homologous recombination. None of
      these appeared to be involved in the island excision. The second model, analyzed
      in a RecA deficient context, was a plasmid construction containing a short direct
      repeat proceeding from Saccharomyces cerevisiae, which flanked the cat gene. The
      excision of this gene by recombination of the DNA repeats was confirmed by PCR
      and through the detection, recovery and characterization of the plasmid deleted
      form. In sum, we present new evidence on the occurrence of RecA-independent
      recombination events in E. coli K12. Although the mechanism underlying these
      processes is still unknown, their existence suggests that RecA-independent
      recombination may confer mobility to other genetic elements, thus contributing to
      genome plasticity.

PMID- 28503376
TI  - Toward a better understanding of the mechanisms of symbiosis: a comprehensive
      proteome map of a nascent insect symbiont.
AB  - Symbiotic bacteria are common in insects and can affect various aspects of their
      hosts' biology. Although the effects of insect symbionts have been clarified for
      various insect symbiosis models, due to the difficulty of cultivating them in
      vitro, there is still limited knowledge available on the molecular features that
      drive symbiosis. Serratia symbiotica is one of the most common symbionts found in
      aphids. The recent findings of free-living strains that are considered as nascent
      partners of aphids provide the opportunity to examine the molecular mechanisms
      that a symbiont can deploy at the early stages of the symbiosis (i.e., symbiotic
      factors). In this work, a proteomic approach was used to establish a
      comprehensive proteome map of the free-living S. symbiotica strain CWBI-2.3T.
      Most of the 720 proteins identified are related to housekeeping or primary
      metabolism. Of these, 76 were identified as candidate proteins possibly promoting
      host colonization. Our results provide strong evidence that S. symbiotica CWBI
      2.3T is well-armed for invading insect host tissues, and suggest that certain
      molecular features usually harbored by pathogenic bacteria are no longer present.
      This comprehensive proteome map provides a series of candidate genes for further
      studies to understand the molecular cross-talk between insects and symbiotic
      bacteria.

PMID- 28503378
TI  - Pollen extracts and constituent sugars increase growth of a trypanosomatid
      parasite of bumble bees.
AB  - Phytochemicals produced by plants, including at flowers, function in protection
      against plant diseases, and have a long history of use against trypanosomatid
      infection. Floral nectar and pollen, the sole food sources for many species of
      insect pollinators, contain phytochemicals that have been shown to reduce
      trypanosomatid infection in bumble and honey bees when fed as isolated compounds.
      Nectar and pollen, however, consist of phytochemical mixtures, which can have
      greater antimicrobial activity than do single compounds. This study tested the
      hypothesis that pollen extracts would inhibit parasite growth. Extracts of six
      different pollens were tested for direct inhibitory activity against cell
      cultures of the bumble bee trypanosomatid gut parasite Crithidia bombi.
      Surprisingly, pollen extracts increased parasite growth rather than inhibiting
      it. Pollen extracts contained high concentrations of sugars, mainly the
      monosaccharides glucose and fructose. Experimental manipulations of growth media
      showed that supplemental monosaccharides (glucose and fructose) increased maximum
      cell density, while a common floral phytochemical (caffeic acid) with inhibitory
      activity against other trypanosomatids had only weak inhibitory effects on
      Crithidia bombi. These results indicate that, although pollen is essential for
      bees and other pollinators, pollen may promote growth of intestinal parasites
      that are uninhibited by pollen phytochemicals and, as a result, can benefit from
      the nutrients that pollen provides.

PMID- 28503379
TI  - A public dataset of running biomechanics and the effects of running speed on
      lower extremity kinematics and kinetics.
AB  - BACKGROUND: The goals of this study were (1) to present the set of data
      evaluating running biomechanics (kinematics and kinetics), including data on
      running habits, demographics, and levels of muscle strength and flexibility made
      available at Figshare (DOI: 10.6084/m9.figshare.4543435); and (2) to examine the
      effect of running speed on selected gait-biomechanics variables related to both
      running injuries and running economy. METHODS: The lower-extremity kinematics and
      kinetics data of 28 regular runners were collected using a three-dimensional (3D)
      motion-capture system and an instrumented treadmill while the subjects ran at 2.5
      m/s, 3.5 m/s, and 4.5 m/s wearing standard neutral shoes. RESULTS: A dataset
      comprising raw and processed kinematics and kinetics signals pertaining to this
      experiment is available in various file formats. In addition, a file of metadata,
      including demographics, running characteristics, foot-strike patterns, and muscle
      strength and flexibility measurements is provided. Overall, there was an effect
      of running speed on most of the gait-biomechanics variables selected for this
      study. However, the foot-strike patterns were not affected by running speed.
      DISCUSSION: Several applications of this dataset can be anticipated, including
      testing new methods of data reduction and variable selection; for educational
      purposes; and answering specific research questions. This last application was
      exemplified in the study's second objective.

PMID- 28503380
TI  - Student evaluations of teaching: teaching quantitative courses can be hazardous
      to one's career.
AB  - Anonymous student evaluations of teaching (SETs) are used by colleges and
      universities to measure teaching effectiveness and to make decisions about
      faculty hiring, firing, re-appointment, promotion, tenure, and merit pay.
      Although numerous studies have found that SETs correlate with various teaching
      effectiveness irrelevant factors (TEIFs) such as subject, class size, and grading
      standards, it has been argued that such correlations are small and do not
      undermine the validity of SETs as measures of professors' teaching effectiveness.
      However, previous research has generally used inappropriate parametric statistics
      and effect sizes to examine and to evaluate the significance of TEIFs on
      personnel decisions. Accordingly, we examined the influence of quantitative vs.
      non-quantitative courses on SET ratings and SET based personnel decisions using
      14,872 publicly posted class evaluations where each evaluation represents a
      summary of SET ratings provided by individual students responding in each class.
      In total, 325,538 individual student evaluations from a US mid-size university
      contributed to theses class evaluations. The results demonstrate that class
      subject (math vs. English) is strongly associated with SET ratings, has a
      substantial impact on professors being labeled satisfactory vs. unsatisfactory
      and excellent vs. non-excellent, and the impact varies substantially depending on
      the criteria used to classify professors as satisfactory vs. unsatisfactory.
      Professors teaching quantitative courses are far more likely not to receive
      tenure, promotion, and/or merit pay when their performance is evaluated against
      common standards.

PMID- 28503381
TI  - A survey of fishes associated with Hawaiian deep-water Halimeda kanaloana
      (Bryopsidales: Halimedaceae) and Avrainvillea sp. (Bryopsidales: Udoteaceae)
      meadows.
AB  - The invasive macroalgal species Avrainvillea sp. and native species Halimeda
      kanaloana form expansive meadows that extend to depths of 80 m or more in the
      waters off of O'ahu and Maui, respectively. Despite their wide depth
      distribution, comparatively little is known about the biota associated with these
      macroalgal species. Our primary goals were to provide baseline information on the
      fish fauna associated with these deep-water macroalgal meadows and to compare the
      abundance and diversity of fishes between the meadow interior and sandy
      perimeters. Because both species form structurally complex three-dimensional
      canopies, we hypothesized that they would support a greater abundance and
      diversity of fishes when compared to surrounding sandy areas. We surveyed the
      fish fauna associated with these meadows using visual surveys and collections
      made with clove-oil anesthetic. Using these techniques, we recorded a total of 49
      species from 25 families for H. kanaloana meadows and surrounding sandy areas,
      and 28 species from 19 families for Avrainvillea sp. habitats. Percent endemism
      was 28.6% and 10.7%, respectively. Wrasses (Family Labridae) were the most
      speciose taxon in both habitats (11 and six species, respectively), followed by
      gobies for H. kanaloana (six species). The wrasse Oxycheilinus bimaculatus and
      cardinalfish Apogonichthys perdix were the most frequently-occurring species
      within the H. kanaloana and Avrainvillea canopies, respectively. Obligate
      herbivores and food-fish species were rare in both habitats. Surprisingly, the
      density and abundance of small epibenthic fishes were greater in open sand than
      in the meadow canopy. In addition, species richness was also higher in open sand
      for Avrainvillea sp. We hypothesize that the dense holdfasts and rhizoids present
      within the meadow canopy may impede benthic-dwelling or bioturbator species,
      which accounted for 86% and 57% of individuals collected in sand adjacent to H.
      kanaloana and Avrainvillea sp. habitats, respectively. Of the 65 unique species
      recorded in this study, 16 (25%) were detected in clove oil stations alone,
      illustrating the utility of clove-oil anesthetic in assessing the diversity and
      abundance of small-bodied epibenthic fishes.

PMID- 28503383
TI  - Social relationships enhance the time spent eating and intake of a novel diet in
      pregnant Hanwoo (Bos taurus coreanae) heifers.
AB  - The objective of this study was to evaluate the effects of social relationships
      on the feed intake, eating behavior, and growth, upon exposure to a novel diet,
      in Hanwoo (Bos taurus coreanae) heifers during pregnancy. Twenty-four pregnant
      Hanwoo heifers, averaging 438 +/- 27.8 kg in weight, 21 months in age, and 194 +/
      8.5 days in pregnancy, were involved in a two-month (eight weeks) experiment.
      The heifers were randomly assigned to either the single housing group (SG; one
      individual per pen, n = 12), or the paired housing group (PG; two individuals per
      pen, n = 12). All pens were of the same size (5 * 5 m) and provided with one feed
      bin, which automatically recorded the individual feed intake and eating behavior.
      As the experiment began, the diet of the heifers was switched from a total mixed
      ration (TMR; 250 g/kg ryegrass straw and 750 g/kg concentrate mix) to a forage
      only diet (mixed hay cubes composed of 500 g/kg alfalfa, 250 g/kg timothy, and
      250 g/kg blue grass hay). The heifers were fed ad libitum twice a day. The
      individual feed intake and eating behavior were recorded daily throughout the
      experiment, and body weights (BWs) were measured every four weeks before the
      morning feeding. PG animals visited the feed bin 22% less often than SG. PG,
      however, stayed 39% longer in the feed bin and consumed 40% more feed per visit,
      compared with SG. Consequently, PG heifers spent 23% more time in eating and had
      16% more daily dry matter intake than SG during the experiment. Average daily
      gain during the experimental period tended to be greater in PG than in SG. When
      pregnant Hanwoo heifers encountered a novel diet, social relationships (i.e.,
      presence of a pen-mate) enhanced their time spent eating and feed intake. Social
      interactions, even with an unfamiliar individual, may be helpful for pregnant
      Hanwoo heifers cope with a diet challenge compared to solitary situation.

PMID- 28503382
TI  - Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered
      in a Charcot-Marie-Tooth-1E neurodegenerative model.
AB  - BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose
      polymerases (PARPs) as a postranslational protein modification and catabolized
      mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of
      cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR,
      demonstrating roles in the maintenance of chromatin architecture and the
      participation in DNA damage responses and transcriptional regulation. We have
      recently detected non-nuclear PAR structurally and functionally associated to the
      E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial
      cells. Myelinating Schwann cells (SC) are stabilized by E-cadherin rich autotypic
      adherens junctions (AJ). We wondered whether PAR would map to these regions.
      Besides, we have demonstrated an altered microfilament pattern in peripheral
      nerves of Trembler-J (Tr-J) model of CMT1-E. We hypothesized that cytoplasmic PAR
      would accompany such modified F-actin pattern. METHODS: Wild-type (WT) and Tr-J
      mice sciatic nerves cryosections were subjected to immunohistofluorescence with
      anti-PAR antibodies (including antibody validation), F-actin detection with a
      phalloidin probe and DAPI/DNA counterstaining. Confocal image stacks were
      subjected to a colocalization highlighter and to semi-quantitative image
      analysis. RESULTS: We have shown for the first time the presence of PAR in
      sciatic nerves. Cytoplasmic PAR colocalized with F-actin at non-compact myelin
      regions in WT nerves. Moreover, in Tr-J, cytoplasmic PAR was augmented in close
      correlation with actin. In addition, nuclear PAR was detected in WT SC and was
      moderately increased in Tr-J SC. DISCUSSION: The presence of PAR associated to
      non-compact myelin regions (which constitute E-cadherin rich autotypic AJ/actin
      anchorage regions) and the co-alterations experienced by PAR and the actin
      cytoskeleton in epithelium and nerves, suggest that PAR may be a constitutive
      component of AJ/actin anchorage regions. Is PAR stabilizing the AJ-actin
      complexes? This question has strong implications in structural cell biology and
      cell signaling networks. Moreover, if PAR played a stabilizing role, such
      stabilization could participate in the physiological control of axonal branching.
      PARP and PAR alterations exist in several neurodegenerative pathologies including
      Alzheimer's, Parkinson's and Hungtington's diseases. Conversely, PARP inhibition
      decreases PAR and promotes neurite outgrowth in cortical neurons in vitro.
      Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and
      in vivo. Until now such results have been interpreted in terms of nuclear PARP
      activity. Our results indicate for the first time the presence of PARylation in
      peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a
      PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs
      and PARylation in normal and neurodegenerative conditions should be re-evaluated.

PMID- 28503384
TI  - Divergent effect of fluoxetine on the response to physical or chemical stressors
      in zebrafish.
AB  - Fluoxetine is a selective serotonin reuptake inhibitor that increases serotonin
      concentration in the central nervous system and modulates various systems,
      including the control of sympathetic outflow and the hypothalamus-pituitary
      adrenal. However, it is not yet established whether fluoxetine can modulate the
      responses to stressors stimulants (physical or chemical) that trigger cortisol
      response in zebrafish. We demonstrate that fluoxetine blunts the response to
      physical stress, but not to chemical stress.

PMID- 28503386
TI  - Mechanical Thrombectomy for Acute Ischemic Stroke After Cardiac Surgery.
AB  - Ischemic stroke is a rare yet devastating complication that may occur following
      cardiothoracic surgery. Fibrinolytic treatment is contraindicated due to elevated
      risk for hemorrhage. Mechanical thrombectomy entails a catheterized approach
      wherein the thrombus is physically removed from the vessel without the use of
      fibrinolytics, minimizing the possibility of intracranial hemorrhage. Here, we
      present two original cases of mechanical thrombectomy as treatment for patients
      experiencing emergent large vessel occlusion following cardiothoracic surgery. A
      literature review was conducted to determine current treatment guidelines, risk
      factors, and complications resulting from recanalization due to mechanical
      thrombectomy versus fibrinolytic therapy. One patient was admitted due to
      chronic, American College of Cardiology/American Heart Association stage D, New
      York Heart Association functional class IV heart failure and required complete,
      artificial hemodynamic support for two weeks and on the 19th day experienced
      neurologic decline secondary to a supraclinoid left internal carotid artery (ICA)
      occlusion. Mechanical thrombectomy resulted in distal reperfusion and neurologic
      improvement. The second patient presented with coronary artery disease and
      underwent triple coronary artery bypass grafting and endovein harvesting. On post
      operative day 2, the patient experienced a left ICA occlusion extending to the
      cavernous ICA resulting in speech impairment and right-sided weakness. The
      patient was heparinized and underwent mechanical thrombectomy, resulting in
      immediate speech and muscle strength recovery. Medical advances allow mechanical
      thrombectomy to be performed in a timely and effective manner at specialized
      treatment centers. It offers endovascular treatment modalities to a unique
      patient population with postoperative stroke. In such patients, thrombectomy can
      safely provide reperfusion while reducing the risk of complications associated
      with conventional thrombolytics.

PMID- 28503385
TI  - Intervention effects of five cations and their correction on hemolytic activity
      of tentacle extract from the jellyfish Cyanea capillata.
AB  - Cations have generally been reported to prevent jellyfish venom-induced hemolysis
      through multiple mechanisms by spectrophotometry. Little attention has been paid
      to the potential interaction between cations and hemoglobin, potentially
      influencing the antagonistic effect of cations. Here, we explored the effects of
      five reported cations, La3+, Mn2+, Zn2+, Cu2+ and Fe2+, on a hemolytic test
      system and the absorbance of hemoglobin, which was further used to measure their
      effects on the hemolysis of tentacle extract (TE) from the jellyfish Cyanea
      capillata. All the cations displayed significant dose-dependent inhibitory
      effects on TE-induced hemolysis with various dissociation equilibrium constant
      (Kd) values as follows: La3+ 1.5 mM, Mn2+ 93.2 mM, Zn2+ 38.6 mM, Cu2+ 71.9 MUM
      and Fe2+ 32.8 mM. The transparent non-selective pore blocker La3+ did not affect
      the absorbance of hemoglobin, while Mn2+ reduced it slightly. Other cations,
      including Zn2+, Cu2+ and Fe2+, greatly decreased the absorbance with Kd values of
      35.9, 77.5 and 17.6 mM, respectively. After correction, the inhibitory Kd values
      were 1.4 mM, 45.8 mM, 128.5 MUM and 53.1 mM for La3+, Zn2+, Cu2+ and Fe2+,
      respectively. Mn2+ did not inhibit TE-induced hemolysis. Moreover, the inhibitory
      extent at the maximal given dose of all cations except La3+ was also diminished.
      These corrected results from spectrophotometry were further confirmed by direct
      erythrocyte counting under microscopy. Our results indicate that the cations,
      except for La3+, can interfere with the absorbance of hemoglobin, which should be
      corrected when their inhibitory effects on hemolysis by jellyfish venoms are
      examined. The variation in the inhibitory effects of cations suggests that the
      hemolysis by jellyfish venom is mainly attributed to the formation of non
      selective cation pore complexes over other potential mechanisms, such as
      phospholipases A2 (PLA2), polypeptides, protease and oxidation. Blocking the pore
      forming complexes may be a primary strategy to improve the in vivo damage and
      mortality from jellyfish stings due to hemolytic toxicity.

PMID- 28503387
TI  - Rubinstein-Taybi Syndrome Associated with Pituitary Macroadenoma: A Case Report.
AB  - Rubinstein-Taybi Syndrome (RSTS) is an autosomal dominant disorder that is
      classically characterized by prenatal and postnatal growth restriction,
      microcephaly, dysmorphic craniofacial features, broad thumbs and toes, and
      intellectual disability. We describe the first reported case of a pituitary
      macroadenoma associated with RSTS. A 39-year-old Caucasian female with a past
      medical history of RSTS diagnosed at age two was found to have a gadolinium
      enhancing pituitary mass on magnetic resonance imaging (MRI) of the brain three
      years ago during workup for migraine-like headaches. Subsequent serial imaging
      showed radiographic evidence of growth up to 11.5 x 14.0 x 10.0 mm in size. The
      pituitary sellar lesion was resected through an endoscopic transnasal
      transsphenoidal approach and was found to be a thyrotroph adenoma. RSTS is a
      rare, neurodevelopmental genetic disease where most patients with disabilities
      survive into adulthood. The disorder is associated with an increased
      predisposition for development of nervous system tumors, including pituitary
      adenomas.

PMID- 28503388
TI  - Pilot Study of 99mTc-labeled Ethylene Dicysteine Deoxyglucose SPECT-CT Imaging in
      Treatment Response Evaluation in Patients with Locally Advanced Head and Neck
      Cancer.
AB  - BACKGROUND: The purpose of this study is to describe the preliminary findings of
      99mTc-labeled ethylene dicysteine deoxyglucose (99mTc-EC-DG) performed four weeks
      after chemoradiotherapy in patients with locally advanced head and neck squamous
      cell carcinoma. METHODS: Review of nine patients with locally advanced head and
      neck squamous cell carcinomas imaged with 99mTc-EC-DG single photon emission
      computed tomography-computed tomography (SPECT-CT) at baseline before treatment
      and at four weeks after treatment completion was performed. RESULTS: At four
      weeks post-treatment, five patients had either decreased activity or no
      significant activity on 99mTc-EC-DG SPECT-CT and were considered to have
      responded to treatment, whereas four patients did not have significantly
      decreased uptake on 99mTc-EC-DG SPECT-CT and were considered to have not
      adequately responded to treatment. Among the five patients considered to have
      treatment response at four weeks, all were free of disease (true-negative). Among
      the four patients considered to have stable activity on 99mTc-EC-DG SPECT-CT at
      four weeks, two were designated as having no response or incomplete response
      (true-positive), and two were designated as having complete response (false
      positive) on subsequent composite assessment. CONCLUSIONS: The pilot data is
      promising but warrants further investigation of 99mTc-EC-DG SPECT-CT for the
      assessment of locoregional treatment response at four weeks in patients with
      locally advanced head and neck squamous cell carcinomas.

PMID- 28503389
TI  - Rosai-Dorfman Disease of the Breast.
AB  - Rosai-Dorfman disease (also known as sinus histiocytosis with massive
      lymphadenopathy) is a rare benign proliferative disorder of histiocytes that
      typically involves the lymph nodes and can also involve extranodal sites. Rosai
      Dorfman disease confined to the breast is extremely rare, but important to
      recognize as it can mimic malignancy. We present the case of a 63-year-old woman
      who presented with a palpable breast lump that was highly suspicious for
      malignancy based on mammogram and ultrasound appearance. Biopsy revealed
      inflammatory tissue with lymphoplasmacytic and histiocytic predominance. The
      diagnosis of Rosai-Dorfman was made based on characteristic staining of
      histiocytes with S-100 and the presence of emperipolesis. Early recognition of
      this benign disease entity spared the patient further investigation and surgical
      intervention.

PMID- 28503390
TI  - The Challenges of Developing a Participatory Arts Intervention for Caregivers of
      Persons with Dementia.
AB  - OBJECTIVE: We describe the development and challenges in implementing a web-based
      participatory art intervention specifically designed for caregivers of persons
      with dementia to use at home with their loved one.   Method: An interprofessional
      team, including an experienced national panel of artists, developed a
      participatory arts toolkit consisting of seven web-based modules involving a
      combination of music, singing, dancing, poetry, and painting. Participants
      completed a survey of demographics, caregiver needs, and caregiver burden. 
      Results: Thirty caregivers with high caregiver needs and a high caregiver burden
      volunteered to pilot the intervention. Difficulties with caregiver recruitment
      and compliance with lesson plans were noted. Caregivers provided positive and
      negative qualitative feedback.   Discussion: The challenges and possible
      solutions to the problems identified in the implementation and assessment of this
      participatory arts intervention will provide important insights for future
      studies linking the arts and dementia care.

PMID- 28503391
TI  - Prevalence and Predictors of Use of Home Sphygmomanometers Among Hypertensive
      Patients.
AB  - OBJECTIVE: Few studies have looked at the predictors of use of home
      sphygmomanometers among hypertensive patients in low-income countries such as
      Pakistan. Considering the importance of home blood pressure monitoring (HBPM),
      cross-sectional study was conducted to evaluate the prevalence and predictors of
      the usage of all kinds of HBPM devices. METHOD: This study was conducted in
      Karachi during the time period of January-February 2017. Adult patients
      previously diagnosed with hypertension visiting tertiary care hospitals were
      selected for the study. Interviews from the individuals were conducted after
      verbal consent using a pre-coded questionnaire. The data was analyzed using
      Statistical Package for the Social Sciences v. 23.0 (SPSS, IBM Corporation, NY,
      USA). Chi-squared test was applied as the primary statistical test. RESULTS: More
      than half of the participants used a home sphygmomanometer (n=250, 61.7%). The
      age, level of education, family history of hypertension, compliance to drugs and
      blood pressure (BP) monitoring, few times a month at clinics were significant
      determinants of HBPM (P values < 0.001). It was found that more individuals owned
      a digital sphygmomanometer (n=128, 51.3%) as compared to a manual type (n=122,
      48.8%). Moreover, avoiding BP measurement in a noisy environment was the most
      common precaution taken (n=117, 46.8%). CONCLUSION: The study showed that around
      40% of the hypertensive individuals did not own a sphygmomanometer and less than
      25% performed HBPM regularly. General awareness by healthcare professionals can
      be a possible factor which can increase HBPM.

PMID- 28503392
TI  - Heritability of Hippocampal Formation Sub-region Volumes.
AB  - BACKGROUND: Hippocampal formation (HF) volume and episodic memory performance are
      substantially heritable, but HF subregion heritability estimates and their
      possible shared genetic variance with episodic memory performance remain to be
      determined. METHODS AND FINDINGS: This study provides heritability estimates for
      hippocampal subregions (e.g, Cornu Amonis, Subiculum, Parasubiculum, Molecular
      and Granule Cell Layers of the Dentate Gryus) and Total HF volumes obtained using
      FreeSurfer 6.0. In addition, this study assesses the heritability of object
      sequence and verbal episodic memory performance, and the amount of shared genetic
      variance between HF subregions and Total HF volume and episodic memory
      performance. HF volumes were obtained from high-resolution brain scans from a
      sample of 499 siblings (mean age+/-SD=30.0+/-3.1, 203 men), including 51
      monozygotic and 46 dizygotic twin pairs and 305 non-twin siblings, collected by
      the Human Connectome Project (www.humanconnectome.org). Heritability estimates
      for HF subregions ranged from 0.42-0.87 and shared genetic variance of HF
      subregions with hippocampal volume was substantial (mean=0.79, range=0.50-0.98).
      HF subregion volumes residualized for Total HF and percent HF subregion volumes
      were also found to be substantially heritable (range=0.04-0.86 and 0.07-0.84,
      respectively). Verbal (h2=0.47) but not object sequence episodic memory was found
      to be significantly heritable; though the amount of shared genetic variance
      between HF subregions and verbal episodic memory was low (mean=0.10, range=0.01
      0.20). CONCLUSIONS: These findings suggest that HF subregion volumes are
      heritable and can be used as quantitative phenotypes in genetic association
      studies. The low shared genetic variance between HF subregions and verbal
      episodic memory suggests that quantitative trait analyses may not benefit from
      including both HF volume and episodic memory as bivariate traits in healthy
      individuals. The extent to which HF subregion volumes share genetic variance with
      neuropsychiatric disorders, and as such add value to our ability to identify
      genetic risk loci for these disorders, remains to be determined.

PMID- 28503393
TI  - Measuring adhesion on rough surfaces using atomic force microscopy with a liquid
      probe.
AB  - We present a procedure to perform and interpret pull-off force measurements
      during the jump-off-contact process between a liquid drop and rough surfaces
      using a conventional atomic force microscope. In this method, a micrometric
      liquid mercury drop is attached to an AFM tipless cantilever to measure the force
      required to pull this drop off a rough surface. We test the method with two
      surfaces: a square array of nanometer-sized peaks commonly used for the
      determination of AFM tip sharpness and a multi-scaled rough diamond surface
      containing sub-micrometer protrusions. Measurements are carried out in a nitrogen
      atmosphere to avoid water capillary interactions. We obtain information about the
      average force of adhesion between a single peak or protrusion and the liquid
      drop. This procedure could provide useful microscopic information to improve our
      understanding of wetting phenomena on rough surfaces.

PMID- 28503395
TI  - The role of 2D/3D spin-polarization interactions in hybrid copper hydroxide
      acetate: new insights from first-principles molecular dynamics.
AB  - The magnetic properties response of the layered hybrid material copper hydroxide
      acetate Cu2(OH)3CH3COO.H2O is studied as a function of the applied pressure
      within first-principles molecular dynamics. We are able to elucidate the
      interplay between the structural properties of this material and its magnetic
      character, both at the local (atomic) level and at the bulk level. We performed a
      detailed analysis of the intralayer spin configurations occurring for each value
      of the imposed projection along the z-axis for the total spin and of the applied
      pressure. The transition from an antiferromagnetic to a ferromagnetic state at
      high pressure (above 3 GPa) goes along with a vanishing difference between the
      spin polarizations pertaining to each layer. Therefore, at high pressure, copper
      hydroxide acetate is a ferromagnet with no changes of spin polarization in the
      direction perpendicular to the inorganic layers.

PMID- 28503396
TI  - Hybrid nanomaterials: from the laboratory to the market.

PMID- 28503394
TI  - Investigation of growth dynamics of carbon nanotubes.
AB  - The synthesis of single-walled carbon nanotubes (SWCNTs) with defined properties
      is required for both fundamental investigations and practical applications. The
      revealing and thorough understanding of the growth mechanism of SWCNTs is the key
      to the synthesis of nanotubes with required properties. This paper reviews the
      current status of the research on the investigation of growth dynamics of carbon
      nanotubes. The review starts with the consideration of the peculiarities of the
      growth mechanism of carbon nanotubes. The physical and chemical states of the
      catalyst during the nanotube growth are discussed. The chirality selective growth
      of nanotubes is described. The main part of the review is dedicated to the
      analysis and systematization of the reported results on the investigation of
      growth dynamics of nanotubes. The studies on the revealing of the dependence of
      the growth rate of nanotubes on the synthesis parameters are reviewed. The
      correlation between the lifetime of catalyst and growth rate of nanotubes is
      discussed. The reports on the calculation of the activation energy of the
      nanotube growth are summarized. Finally, the growth properties of inner tubes
      inside SWCNTs are considered.

PMID- 28503397
TI  - Relationships between chemical structure, mechanical properties and materials
      processing in nanopatterned organosilicate fins.
AB  - The exploitation of nanoscale size effects to create new nanostructured materials
      necessitates the development of an understanding of relationships between
      molecular structure, physical properties and material processing at the
      nanoscale. Numerous metrologies capable of thermal, mechanical, and electrical
      characterization at the nanoscale have been demonstrated over the past two
      decades. However, the ability to perform nanoscale molecular/chemical structure
      characterization has only been recently demonstrated with the advent of atomic
      force-microscopy-based infrared spectroscopy (AFM-IR) and related techniques.
      Therefore, we have combined measurements of chemical structures with AFM-IR and
      of mechanical properties with contact resonance AFM (CR-AFM) to investigate the
      fabrication of 20-500 nm wide fin structures in a nanoporous organosilicate
      material. We show that by combining these two techniques, one can clearly observe
      variations of chemical structure and mechanical properties that correlate with
      the fabrication process and the feature size of the organosilicate fins.
      Specifically, we have observed an inverse correlation between the concentration
      of terminal organic groups and the stiffness of nanopatterned organosilicate
      fins. The selective removal of the organic component during etching results in a
      stiffness increase and reinsertion via chemical silylation results in a stiffness
      decrease. Examination of this effect as a function of fin width indicates that
      the loss of terminal organic groups and stiffness increase occur primarily at the
      exposed surfaces of the fins over a length scale of 10-20 nm. While the observed
      structure-property relationships are specific to organosilicates, we believe the
      combined demonstration of AFM-IR with CR-AFM should pave the way for a similar
      nanoscale characterization of other materials where the understanding of such
      relationships is essential.

PMID- 28503398
TI  - Synthesis of coaxial nanotubes of polyaniline and poly(hydroxyethyl methacrylate)
      by oxidative/initiated chemical vapor deposition.
AB  - Vapor-phase synthesis techniques of polymeric nanostructures offer unique
      advantages over conventional, solution-based techniques because of their
      solventless nature. In this work, we report the fabrication of coaxial polymer
      nanotubes using two different chemical vapor deposition methods. The fabrication
      process involves the deposition of an outer layer of the conductive polyaniline
      (PANI) by oxidative chemical vapor deposition, followed by the deposition of the
      inner layer of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel by initiated
      chemical vapor deposition. The vapor-phase techniques allowed for fine-tuning of
      the thickness of the individual layers, keeping the functionalities of the
      polymers intact. The response of the single components and the coaxial nanotubes
      to changes in humidity was investigated for potential humidity sensor
      applications. For single-component conductive PANI nanotubes, the resistance
      changed parabolically with relative humidity because of competing effects of
      doping and swelling of the PANI polymer under humid conditions. Introducing a
      hydrogel inner layer increased the overall resistance, and enhanced swelling,
      which caused the resistance to continuously increase with relative humidity.

PMID- 28503399
TI  - Functional dependence of resonant harmonics on nanomechanical parameters in
      dynamic mode atomic force microscopy.
AB  - We present a combined theoretical and experimental study of the dependence of
      resonant higher harmonics of rectangular cantilevers of an atomic force
      microscope (AFM) as a function of relevant parameters such as the cantilever
      force constant, tip radius and free oscillation amplitude as well as the
      stiffness of the sample's surface. The simulations reveal a universal functional
      dependence of the amplitude of the 6th harmonic (in resonance with the 2nd
      flexural mode) on these parameters, which can be expressed in terms of a gun
      shaped function. This analytical expression can be regarded as a practical tool
      for extracting qualitative information from AFM measurements and it can be
      extended to any resonant harmonics. The experiments confirm the predicted
      dependence in the explored 3-45 N/m force constant range and 2-345 GPa sample's
      stiffness range. For force constants around 25 N/m, the amplitude of the 6th
      harmonic exhibits the largest sensitivity for ultrasharp tips (tip radius below
      10 nm) and polymers (Young's modulus below 20 GPa).

PMID- 28503400
TI  - Triptycene-terminated thiolate and selenolate monolayers on Au(111).
AB  - To study the implications of highly space-demanding organic moieties on the
      properties of self-assembled monolayers (SAMs), triptycyl thiolates and
      selenolates with and without methylene spacers on Au(111) surfaces were
      comprehensively studied using ultra-high vacuum infrared reflection absorption
      spectroscopy, X-ray photoelectron spectroscopy, near-edge X-ray absorption fine
      structure spectroscopy and thermal desorption spectroscopy. Due to packing
      effects, the molecules in all monolayers are substantially tilted. In the
      presence of a methylene spacer the tilt is slightly less pronounced. The
      selenolate monolayers exhibit smaller defect densities and therefore are more
      densely packed than their thiolate analogues. The Se-Au binding energy in the
      investigated SAMs was found to be higher than the S-Au binding energy.

PMID- 28503401
TI  - Bio-inspired micro-to-nanoporous polymers with tunable stiffness.
AB  - Background: Inspired by structural hierarchies and the related excellent
      mechanical properties of biological materials, we created a smoothly graded micro
      to nanoporous structure from a thermoplastic polymer. Results: The viscoelastic
      properties for the different pore sizes were investigated in the glassy regime by
      dynamic flat-punch indentation. Interestingly, the storage modulus was observed
      to increase with increasing pore-area fraction. Conclusion: This outcome appears
      counterintuitive at first sight, but can be rationalized by an increase of the
      pore wall thickness as determined by our quantitative analysis of the pore
      structure. Therefore, our approach represents a non-chemical way to tune the
      elastic properties and their local variation for a broad range of polymers by
      adjusting the pore size gradient.

PMID- 28503403
TI  - Diagnostics in Hymenoptera venom allergy: current concepts and developments with
      special focus on molecular allergy diagnostics.
AB  - BACKGROUND: The high rate of asymptomatic sensitization to Hymenoptera venom,
      difficulty in correctly identifying Hymenoptera and loss of sensitization over
      time make an accurate diagnosis of Hymenoptera venom allergy challenging.
      Although routine diagnostic tests encompassing skin tests and the detection of
      venom-specific IgE antibodies with whole venom preparations are reliable, they
      offer insufficient precision in the case of double sensitized patients or in
      those with a history of sting anaphylaxis, in whom sensitization cannot be proven
      or only to the presumably wrong venom. METHODS: Systematic literature research
      and review of current concepts of diagnostic testing in Hymenoptera venom
      allergy. RESULTS AND DISCUSSION: Improvements in diagnostic accuracy over recent
      years have mainly been due to the increasing use of molecular allergy
      diagnostics. Detection of specific IgE antibodies to marker and cross-reactive
      venom allergens improves the discrimination between genuine sensitization and
      cross-reactivity, and this provides a better rationale for prescribing venom
      immunotherapy. The basophil activation test has also increased diagnostic
      accuracy by reducing the number of Hymenoptera venom sensitizations overlooked
      with routine tests. This paper reviews current concepts of diagnostic testing in
      Hymenoptera venom allergy and suggests fields for further development.

PMID- 28503402
TI  - Physical Exercise for Treatment of Mood Disorders: A Critical Review.
AB  - PURPOSE OF THE REVIEW: The purpose of this review is to critically assess the
      evidence for exercise as an adjunct intervention for major depressive disorder
      and bipolar disorder, chronic conditions characterized by frequent comorbid
      conditions as well as interepisodic symptoms with poor quality of life and
      impaired functioning. Individuals with these mood disorders are at higher risk of
      cardiovascular disease and premature death in part because of increased rates of
      obesity, inactivity, and diabetes mellitus compared to the general population.
      Exercise may not only mitigate the increased risk of cardiovascular disease, but
      could also potentially improve the long term outcomes of mood disorders. RECENT
      FINDINGS: We conducted a literature review on the impact of exercise on mood
      disorders and associated comorbid conditions as well as possible biological
      mechanisms. We found that exercise impacts both the physical health parameters of
      mood disorders as well as mental health outcomes. Exercise also positively
      impacts conditions frequently comorbid with mood disorders (i.e. anxiety, pain,
      and insomnia). There are multiple candidate biomarkers for exercise, with brain
      derived neurotrophic factor and oxidative stress as two main promising components
      of exercise's anti-depressant effect. SUMMARY: Exercise appears to be a promising
      adjunct treatment for mood disorders. We conclude with recommendations for future
      research of exercise as an adjunct intervention for mood disorders.

PMID- 28503405
TI  - Nanoparticle Design Strategies for Effective Cancer Immunotherapy.
AB  - Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment
      modality that adds a strong tool to the collective cancer treatment arsenal. It
      can be effective even for late stage diagnoses and has already received clinical
      approval. Tumors are known to not only avoid immune surveillance but also exploit
      the immune system to continue local tumor growth and metastasis. Because of this,
      most immunotherapies, particularly those directed against solid cancers, have
      thus far only benefited a small minority of patients. Early clinical
      substantiation lends weight to the claim that cancer immunotherapies, which are
      adaptive and enduring treatment methods, generate much more sustained and robust
      anticancer effects when they are effectively formulated in nanoparticles or
      scaffolds than when they are administered as free drugs. Engineering cancer
      immunotherapies using nanomaterials is, therefore, a very promising area worthy
      of further consideration and investigation. This review focuses on the recent
      advances in cancer immunoengineering using nanoparticles for enhancing the
      therapeutic efficacy of a diverse range of immunotherapies. The delivery of
      immunostimulatory agents to antitumor immune cells, such as dendritic or antigen
      presenting cells, may be a far more efficient tactic to eradicate tumors than
      delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In
      addition to its immense therapeutic potential, immunoengineering using
      nanoparticles also provides a valuable tool for unearthing and understanding the
      basics of tumor biology. Recent research using nanoparticles for cancer
      immunotherapy has demonstrated the advantage of physicochemical manipulation in
      improving the delivery of immunostimulatory agents. In vivo studies have tested a
      range of particle sizes, mostly less than 300 nm, and particles with both
      positive and negative zeta potentials for various applications. Material
      composition and surface modifications have been shown to contribute significantly
      in selective targeting, efficient delivery and active stimulation of immune
      system targets. Thus, these investigations, including a wide array of
      nanoparticles for cancer immunotherapy, substantiate the employment of
      nanocarriers for efficacious cancer immunotherapies.

PMID- 28503407
TI  - Potential in vitro model for testing the effect of exposure to nanoparticles on
      the lung alveolar epithelial barrier.
AB  - Pulmonary barrier function plays a pivotal role in protection from inhaled
      particles. However, some nano-scaled particles, such as carbon nanotubes (CNT),
      have demonstrated the ability to penetrate this barrier in animal models,
      resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying
      mechanism and specific bio-effect of inhaled nanoparticles in respiratory
      toxicity, models of lung epithelial barriers are required that allow accurate
      representation of in vivo systems; however, there is currently a lack of
      consistent methods to do so. Thus, this work demonstrates a well-characterized in
      vitro model of pulmonary barrier function using Calu-3 cells, and provides the
      experimental conditions required for achieving tight junction complexes in cell
      culture, with trans-epithelial electrical resistance measurement used as a
      biosensor for proper barrier formation and integrity. The effects of cell number
      and serum constituents have been examined and we found that changes in each of
      these parameters can greatly affect barrier formation. Our data demonstrate that
      use of 5.0 * 104 Calu-3 cells/well in the Transwell cell culture system, with 10%
      serum concentrations in culture media is optimal for assessing epithelial barrier
      function. In addition, we have utilized CNT exposure to analyze the dose-, time-,
      and nanoparticle property-dependent alterations of epithelial barrier
      permeability as a means to validate this model. Such high throughput in vitro
      cell models of the epithelium could be used to predict the interaction of other
      nanoparticles with lung epithelial barriers to mimic respiratory behavior in
      vivo, thus providing essential tools and bio-sensing techniques that can be
      uniformly employed.

PMID- 28503404
TI  - Wnt Signaling in Normal and Malignant Stem Cells.
AB  - Wnt signaling plays important roles in stem cell self-renewal and differentiation
      in adults as well as in embryonic development. Mutations that activate canonical
      Wnt/beta-catenin signaling also initiate and maintain several cancer states,
      including colorectal cancer and leukemia, and hence Wnt inhibitors are currently
      being explored as therapeutic options. In this review, we summarize previous
      studies and update recent findings on canonical Wnt signaling and its components,
      as well as their roles in somatic stem cell homeostasis and maintenance of cancer
      initiating cells.

PMID- 28503408
TI  - Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic
      reactive nitrogen formation in mice and in freshly isolated hepatocytes.
AB  - The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N
      acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts.
      Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric
      oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs
      with inhibited mitochondrial function. We previously reported that in hepatocytes
      the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and
      oxygen species formation, and mitochondrial dysfunction. In this work we examined
      the effect of trifluoperazine (TFP), a calmodulin antagonist that inhibits
      calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen
      formation in murine hepatocytes and in vivo. In freshly isolated hepatocytes TFP
      inhibited APAP induced toxicity, reactive nitrogen formation (NO, GSNO, and 3
      nitrotyrosine in protein), reactive oxygen formation (superoxide), loss of
      mitochondrial membrane potential, decreased ATP production, decreased oxygen
      consumption rate, and increased NADH accumulation. TFP did not alter APAP induced
      GSH depletion in the hepatocytes or the formation of APAP protein adducts which
      indicated that reactive metabolite formation was not inhibited. Since we
      previously reported that TFP inhibits the hepatotoxicity of APAP in mice without
      altering hepatic APAP-protein adduct formation, we examined the APAP treated
      mouse livers for evidence of reactive nitrogen formation. 3-Nitrotyrosine in
      hepatic proteins and GSNO were significantly increased in APAP treated mouse
      livers and decreased in the livers of mice treated with APAP plus TFP. These data
      are consistent with a hypothesis that APAP hepatotoxicity occurs with altered
      calcium metabolism, activation of nNOS leading to increased reactive nitrogen
      formation, and mitochondrial dysfunction.

PMID- 28503409
TI  - Taming immune suppressor: application of myeloid-derived suppressor cells in anti
      cancer gene therapy.

PMID- 28503406
TI  - Sleep in Neurodevelopmental Disorders.
AB  - Individuals with intellectual and developmental disabilities (IDD) experience
      sleep problems at higher rates than the general population. Although individuals
      with IDD are a heterogeneous group, several sleep problems cluster within genetic
      syndromes or disorders. This review summarizes the prevalence of sleep problems
      experienced by individuals with Angelman syndrome, Cornelia de Lange syndrome,
      Cri du Chat syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome,
      Smith-Magenis syndrome, Williams syndrome, autism spectrum disorder, and
      idiopathic IDD. Factors associated with sleep problems and the evidence for sleep
      treatments are reviewed for each neurodevelopmental disorder. Sleep research
      advancements in neurodevelopmental disorders are reviewed, including the need for
      consistency in defining and measuring sleep problems, considerations for research
      design and reporting of results, and considerations when evaluating sleep
      treatments.

PMID- 28503410
TI  - The ideal substitute for tricuspid valve replacement in patients with congenital
      heart disease: an unsolved dilemma.

PMID- 28503411
TI  - Ascending aortic slide for interrupted aortic arch repair: a new approach to
      maintain native tissue continuity.

PMID- 28503412
TI  - Editorial on "vascular ring diagnosis and management: notable trends over 25
      years".

PMID- 28503413
TI  - The feeding conundrum.

PMID- 28503414
TI  - Adult-onset deletion of the Prader-Willi syndrome susceptibility gene Snord116 in
      mice results in reduced feeding and increased fat mass.
AB  - BACKGROUND: The imprinted small nucleolar RNA (snoRNA) Snord116 is implicated in
      the aetiology of Prader-Willi syndrome (PWS), a disease associated with
      hyperphagia and obesity. Germline deletion of Snord116 in mice has been found to
      lead to increased food intake but not to the development of obesity. To determine
      the role of Snord116 independent of potential compensatory developmental factors,
      we investigated the effects of conditional adult-onset deletion of Snord116 in
      mice. METHODS: Deletion of Snord116 was induced at 8 weeks of age by oral
      administration of tamoxifen to male Snordlox/lox; ROSAcre/+ mice, with vehicle
      treated mice used as controls. Body weight (BW) was monitored weekly and body
      composition was measured by dual-energy X-ray absorptiometry and tissue
      dissection. Non-fasted and fasting-induced food intake was determined, and
      glucose and insulin tolerance tests were performed. Twenty-four-hour energy
      expenditure and physical activity were assessed by indirect calorimetry. RESULTS:
      Adult-onset deletion of Snord116 led to reduced food intake and increased
      adiposity, albeit with no concomitant change in BW or lean mass compared to
      controls. Adult onset Snord116 deletion was also associated with worsened glucose
      tolerance and insulin sensitivity. CONCLUSIONS: This study identified a key role
      for Snord116 in feeding behaviour and growth. Further, it is likely that the
      effects of this gene are modulated by developmental stage, as mice with adult
      onset deletion showed an opposite phenotype, with respect to food intake and body
      composition, to previously published data on mice with germline deletion.

PMID- 28503415
TI  - Kickboxing power hour: case report of fifth metatarsal apophysitis (Iselin
      disease) and its magnetic resonance imaging features.
AB  - Youth now-a-days are getting more involved in mixed martial arts, with increasing
      number of cases of lateral foot pain due to various causes. The differential
      diagnoses of lateral foot pain in the pediatric population include avulsion
      fracture of the fifth metatarsal base, Jones fracture, diaphyseal stress fracture
      as well as os vesalianum pedis. We present a case of a 15-year-old athletic boy
      who presented with left lateral foot pain for a few weeks. The patient was
      actively involved in Kickboxing as well as active running. Left foot radiographs
      were normal, including normal radiographic appearance of the fifth metatarsal
      apophysis. Due to ongoing pain, magnetic resonance imaging of the left foot was
      performed, which revealed apophysitis of the fifth metatarsal, known as Iselin
      disease. Iselin disease has been postulated to be caused by traction on the fifth
      metatarsal apophysis by performing sidekicks or round kicks during the kickboxing
      practice. Iselin disease should be suspected in young children of 10-15 years age
      involved in physical activity presenting with lateral foot pain. Magnetic
      resonance imaging is extremely useful to correctly diagnose this condition and
      avoid misdiagnosis of a fracture.

PMID- 28503416
TI  - A case of Raoultella planticola causing a urinary tract infection in a pediatric
      patient.
AB  - Raoultella planticola (R. planticola) is an abundant environmental bacterium that
      rarely infects humans. There is only one known case of R. planticola causing a
      urinary tract infection (UTI) in a pediatric patient. This is a second case of R.
      planticola potentially causing a symptomatic UTI in a 2-month-old female child
      with no known medical problems.

PMID- 28503418
TI  - Clown therapy: not only a pediatric matter.

PMID- 28503417
TI  - Indoor/outdoor not-voluptuary-habit pollution and sleep-disordered breathing in
      children: a systematic review.
AB  - BACKGROUND: Exposure to environmental pollutants is advocated to be a major risk
      factor, with increased morbidity and mortality in humans due to acute and chronic
      airway inflammation. The aim of the present review is to show the literature
      research regarding the link between the sleep-disordered breathing and exposure
      to indoor/outdoor pollution in children. We hypothesized that environmental air
      pollution can play a role in childhood sleep-disordered breathing. METHODS: We
      conducted an electronic search in Medline (with PubMed interface), Scopus and the
      ISI Web of Science using the keywords "sleep" or "sleep apnea" or "sleep
      disordered breathing" and "pollution" and "children" in
      "Title/Abstract/Keywords", with language restriction (non-English paper) and no
      date limitation to present. The tobacco smoke pollution is well established
      linking and is not considered for the present subject. We examined the strength
      of the evidence according to the Oxford Centre for Evidence-Based Medicine [2011]
      and the Centre for Evidence-Based Medicine [2009]. RESULTS: A total of 105
      articles were identified, but 97 of these had to be excluded after an accurate
      reading of the title, abstract or full text. In the end, eight studies were
      selected for our analysis for a total of a total of 5,826 children. The results
      suggest an involvement (grade C) of environmental (not from voluptuary habits)
      pollution in the worsening of sleep-disordered breathing in children.
      CONCLUSIONS: To date, some studies reported significant differences between areas
      with higher and lower pollutants and the interventions on indoor pollution
      reduced sleep-disordered breathing in children. Therefore, although the relevance
      of the argument is high, the number of studies and the interest in the subject
      seems at this time quite limited.

PMID- 28503419
TI  - Comparison of the impact of epigallocatechin gallate and ellagic acid in an
      experimental cataract model induced by sodium selenite.
AB  - AIM: To compare the potential protective effects of epi-gallocatechin gallate
      (EGCG) and ellagic acid (EA) in an experimental cataract model. METHODS: Twenty
      eight Spraque-Dawley rat pups were assigned into four groups. All the rats,
      except for those in the control group, were injected subcutaneously sodium
      selenite to induce experimental cataract on the postpartum ninth day, and between
      10th and 14th days. Rats in the sham, EGCG, and EA groups were intraperitoneally
      administered 50 mg/(kg.d) saline solution, 50 mg/(kg.d) EGCG and 200 mg/(kg.d)
      EA, respectively. The reduced glutathione (GSH) and malondialdehyde (MDA) levels,
      total antioxidant status (TAS) and total oxidant status (TOS) in lens
      supernatants were measured. RESULTS: The mean cataract gradings in EGCG and EA
      groups were found to be significantly lower than that in sham group (P<0.001).
      The mean GSH levels and TASs in EGCG and EA groups were significantly higher than
      that in sham group while mean MDA levels and TOSs in EGCG and EA groups were
      significantly lower than that in the sham group (P<0.001). CONCLUSION: EGCG and
      EA have protective effects on cataract development via the inhibition of
      oxidative stress.

PMID- 28503420
TI  - Oxidative stress affects retinal pigment epithelial cell survival through
      epidermal growth factor receptor/AKT signaling pathway.
AB  - AIM: To investigate the cross-talk between oxidative stress and the epidermal
      growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial
      (RPE) cells. METHODS: Human RPE cell lines (ARPE-19 cell) were treated with
      different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2).
      Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell
      proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay.
      EGFR/AKT signaling was detected by Western blot. EGFR localization was also
      detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened
      upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK
      2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N
      acetylcysteine (NAC). RESULTS: EGF treatment increased ARPE-19 cell viability and
      proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited
      ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated
      increase of RPE cell viability and proliferation by affecting the EGFR/AKT
      signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation
      of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation
      of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by
      H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition
      of ARPE-19 cell viability through alleviating reduction of EGFR, and
      phosphorylated and total AKT proteins. CONCLUSION: Oxidative stress affects RPE
      cell viability and proliferation through interfering with the EGFR/AKT signaling
      pathway. The EGFR/AKT signaling pathway may be an important target in oxidative
      stress-induced RPE cell dysfunction.

PMID- 28503422
TI  - Inhibition of cell proliferation, migration and apoptosis in blue-light
      illuminated human retinal pigment epithelium cells by down-regulation of HtrA1.
AB  - AIM: To investigate the effect of HtrA1 on the proliferation, migration and
      apoptosis of human retinal pigment epithelium (RPE) cells in the light injured
      model, as well as the expression of the apoptosis related molecules. METHODS: The
      human RPE cell line ARPE-19 was exposed to blue light to establish the light
      injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1
      expression. Subsequent expression of HtrA1 was determined by real-time polymerase
      chain reaction (RT-PCR) and Western blot, respectively. Changes in cell
      proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK
      8), Transwell assay and flow cytometry respectively, as well as changes in the
      mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1
      was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of
      HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue
      light-irradiated ARPE-19 cells (P<0.05). Bax and Caspase-3 expression were
      significantly reduced both at mRNA and protein levels (P<0.05) after siRNA
      treatment. Bcl-2 expression significantly increased in blue-light-irradiated ARPE
      19 cells after siRNA interference (P<0.05). CONCLUSION: Silence of HtrA1 may
      inhibit the proliferation, migration and apoptosis of ARPE-19 cells in light
      injured model. Moreover, HtrA1 suppression in blue-light-irradiated ARPE-19 cells
      may ameliorate cell apoptosis through down-regulation of Bax and Caspase-3, and
      up-regulation of Bcl-2 expression.

PMID- 28503421
TI  - Differential expression of breast cancer-resistance protein, lung resistance
      protein, and multidrug resistance protein 1 in retinas of streptozotocin-induced
      diabetic mice.
AB  - AIM: To investigate the altering expression profiles of efflux transporters such
      as breast cancer-resistance protein (BCRP), lung resistance protein (LRP), and
      multidrug resistance protein 1 (MDR1) at the inner blood-retinal barrier (BRB)
      during the development of early diabetic retinopathy (DR) and/or aging in mice.
      METHODS: Relative mRNA and protein expression profiles of these three efflux
      transporters in the retina during the development of early DR and/or aging in
      mice were examined. The differing expression profiles of Zonula occludens 1 (ZO
      1) and vascular endothelial growth factor-A (VEGFA) in the retina as well as the
      perfusion characterization of fluorescein isothiocyanate (FITC)-dextran and Evans
      blue were examined to evaluate the integrity of the inner BRB. RESULTS: There
      were significant alterations in these three efflux transporters' expression
      profiles in the mRNA and protein levels of the retina during the development of
      diabetes mellitus and/or aging. The development of early DR was confirmed by the
      expression profiles of ZO-1 and VEGFA in the retina as well as the compromised
      integrity of the inner BRB. CONCLUSION: The expression profiles of some efflux
      transporters such as BCRP, LRP, and MDR1 in mice retina during diabetic and/or
      aging conditions are tested, and the attenuated expression of BCRP, LRP, and MDR1
      along with the breakdown of the inner BRB is found, which may be linked to the
      pathogenesis of early DR.

PMID- 28503423
TI  - MicroRNA-126: a promising novel biomarker in peripheral blood for diabetic
      retinopathy.
AB  - AIM: To investigate the content of serum microRNA-126 (miR-126) and its role in
      screening retinal endothelial injury and early diagnosis of proliferative
      diabetic retinopathy. METHODS: The study included 184 serum samples, 59 samples
      from healthy individuals, 44 samples from diabetes mellitus (DM) patients without
      diabetic retinopathy (NDR), 42 from non-proliferative diabetic retinopathy (NPDR)
      patients and 39 samples from proliferative diabetic retinopathy (PDR) patients.
      The expression of miR-126 was evaluated using a real-time quantitative polymerase
      chain reaction. RESULTS: The serum content of miR-126 declined as the damage
      degree in the retina. There was significant difference between the two
      retinopathy groups (P<0.001). No difference was observed in miR-126 content
      between healthy individuals and NDR patients (P>0.05). Receiver operating
      characteristic curve (ROC) analyses indicated that serum miR-126 had significant
      diagnostic value for PDR. It yielded an area under the curve (AUC) of ROC of
      0.976 with 81.21% sensitivity and 90.34% specificity in discriminating PDR from
      healthy controls, and an AUC of ROC of 0.919 with 84.75% sensitivity and 94.41%
      specificity in discriminating NDR and NPDR from healthy controls. When the
      diagnostic threshold was greater than or equal to 8.43, there was an increase in
      the possibility of NPDR. When the content of miR-126 was less than or equal to
      5.02, the possibility of the occurrence of PDR increased. CONCLUSION: Serum miR
      126 can serve as a non-invasive biomarker for screening retinal endothelial
      injury and early diagnosis PDR.

PMID- 28503424
TI  - Interleukin-13 and age-related macular degeneration.
AB  - AIM: o identify the effects of interleukin (IL)-13 on retinal pigment epithelial
      (RPE) cells and the IL-13 level in aqueous humor of age-related macular
      degeneration (AMD) patients. METHODS: IL-13 levels in aqueous humor specimens
      from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA).
      ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell
      proliferaton was evaluated by the MTS method. The mRNA and protein levels of
      alpha-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain
      reaction (qRT-PCR) and Western blot respectively. The expression of tumor
      necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and
      vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL-13
      levels in the aqueous humor of patients with AMD were significantly higher than
      those in the control (167.33+/-17.64 vs 27.12+/-5.65 pg/mL; P<0.01). In vitro, IL
      13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell
      proliferation. alpha-SMA mRNA in ARPE-19 cell were increased (1.017+/-0.112 vs
      1.476+/-0.168; P<0.001) and ZO-1 decreased (1.051+/-0.136 vs 0.702+/-0.069;
      P<0.001) after treated with 10 ng/mL IL-13 for 48h. The protein expression of
      alpha-SMA and ZO-1 also showed the same tendency (alpha-SMA: P=0.038; ZO-1:
      P=0.008). IL-13 significantly reduced the level of TNF-alpha (44.70+/-1.67 vs
      31.79+/-3.53 pg/mL; P=0.005) at 48h, but the level of TGF-beta2 was significantly
      increased from 34.44+/-2.92 to 57.61+/-6.31 pg/mL at 24h (P=0.004) and from
      61.26+/-1.11 to 86.91+/-3.59 pg/mL at 48h (P<0.001). While expressions of VEGF
      didn't change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19
      cell proliferation and expression in the aqueous may be associated with AMD.

PMID- 28503425
TI  - Neuroprotective effects of gypenosides in experimental autoimmune optic neuritis.
AB  - AIM: To determine whether gypenosides have protective effects in experimental
      autoimmune optic neuritis (EAON). METHODS: Mice were randomly divided into seven
      groups: control group, model group, three different density gypenosides
      monotherapy, methylprednisolone monotherapy, combination of gypenosides and
      methylprednisolone group. The control group was subcutaneously injected with oil
      emulsion adjuvant and all other groups were subcutaneously immunized with an
      emulsified mixture of myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to
      induce EAON. Mice in the gypenosides groups were administered injections daily
      with three concentrations (15 mg/kg, 30 mg/kg, 45 mg/kg) of gypenosides
      respectively. Mice in the methylprednisolone group and the combination treatment
      group were injected daily with methylprednisolone (20 mg/kg) or
      methylprednisolone (20 mg/kg) + gypenosides (30 mg/kg), respectively. After MOG
      immunization, visual evoked potential (VEP), optical coherence tomography (OCT),
      and histopathologic examination were performed at 14, 20, 30, and 40d post
      inoculation (p.i.). All results were expressed as mean+/-SEM. The data were
      evaluated by one-way ANOVA followed by Tukey or Games-Howell test. RESULTS:
      Compared with the control group, p2 latency was prolonged in the model group
      (P=0.041). Combination treatment can alleviated the change in VEP at 20d p.i.
      (P=0.012). Average peripapillary retinal nerve fiber layer (RNFL) thickness was
      reduced in the model group (P=0.000, 30d; P=0.000, 40d) and gypenosides treatment
      remarkably diminished the degree of RNFL degeneration at 30d and 40d p.i
      (P=0.000, 30d; P=0.000, 40d). The pathomorphological results showed a decrease in
      demye-lination (P=0.020) and inflammatory reactions in the combination group
      compared with the model group (20d p.i.). Gypenosides treatment also alleviated
      the degree of axonal loss (40d p.i.) (P=0.003). CONCLUSION: Treatment with
      gypenosides exerts protective effects on retinal nerve fibers and axons in EAON.
      When combined with gypenosides, methylprednisolone reduces demyelination in the
      acute stage of EAON.

PMID- 28503426
TI  - Expression and role of specificity protein 1 in the sclera remodeling of
      experimental myopia in guinea pigs.
AB  - AIM: To study the expression of collagen I and transcription factor specificity
      protein 1 (Sp1), a transforming growth factor-beta1 (TGF-beta1) downstream
      target, and reveal the impact of the TGF-beta1-Sp1 signaling pathway on collagen
      remodeling in myopic sclera. METHODS: Seventy-five 1-week-old guinea pigs were
      randomly divided into normal control, form deprivation myopia (FDM), and self
      control groups. FDM was induced for different times using coverage with
      translucent latex balloons and FDM recovery was performed for 1wk after 4wk
      treatment; then, changes in refractive power and axial length were measured.
      Immunohistochemistry and reverse transcription-polymerase chain reaction were
      used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera
      of guinea pigs with emmetropia and experimental myopia, and the relationship
      between collagen I and Sp1 levels was analyzed. RESULTS: In the FDM group, the
      refractive power was gradually changed (from 2.09+/-0.30 D at week 0 to -1.23+/
      0.69 D, -4.17+/-0.59 D, -7.07+/-0.56 D, and -4.30+/-0.58 D at weeks 2, 4, 6, and
      1wk after 4wk, respectively; P<0.05), indicating deepening of myopia. The axial
      length was increased (from 5.92+/-0.39 mm at week 0 to 6.62+/-0.36 mm, 7.30+/
      0.34 mm, 7.99+/-0.32 mm, and 7.41+/-0.36 mm at weeks 2, 4, 6, and 1wk after 4wk;
      P<0.05). The mRNA and protein expression of Sp1 and collagen I in the sclera of
      the FDM group was lower than that of the control groups (P<0.05), and the
      reduction was eye-coverage time-dependent. Furthermore, correlation between Sp1
      and collagen I down-regulation in the myopic sclera was observed. CONCLUSION: Our
      data indicate that transcription factor Sp1 may be involved in the regulation of
      type I collagen synthesis/degradation during myopic sclera remodeling, suggesting
      that TGF-beta1 signaling plays a role in the development and progression of
      myopia.

PMID- 28503427
TI  - Expressions of matrix metalloproteinases 1 and 3 and their tissue inhibitors in
      the conjunctival tissue and fibroblasts cultured from conjunctivochalasis.
AB  - AIM: To investigate the expression of matrix metalloproteinases 1 and 3 (MMP-1
      and MMP-3) and their tissue inhibitors of metalloproteinases 1 and 3 (TIMP-1 and
      TIMP-3) in the conjunctiva of eyes with conjunctivochalasis (CCh). METHODS: The
      conjunctival tissue was obtained from the CCh patients and controls, the
      MMPs/TIMPs expression concentration was determined by enzyme-linked immuno
      sorbent assay (ELISA) and immunofluorescence staining. The expression levels of
      MMPs/TIMPs in the CCh fibro-blasts were determined by analyzing its concentration
      in the cellular supernatant that was abstracted from the in vitro cultured CCh
      fibroblasts. RESULTS: MMP-1 and MMP-3 levels determined by ELISA were both
      significantly higher in the CCh group than that in the control group (P=0.042,
      0.022, respectively), so was the levels of TIMP-1 (P=0.010). No significant
      difference in the expression of TIMP-3 in conjunctiva was found between the two
      groups (P=0.298). The expression of MMP-1 and MMP-3 were both up-regulated
      significantly in the CCh group (P=0.040, 0.001, respectively) on immuno
      fluorescence staining. MMP-1 and MMP-3 expression in the fibroblasts were both
      significantly higher in the CCh group than that in the control group (P=0.027,
      0.001, respectively), while neither the TIMP-1 nor TIMP-3 expression was
      significantly different between the two groups (P=0.421, 0.237, respectively).
      CONCLUSION: The overexpression of MMP-1 and MMP-3 in conjunctival tissue and
      fibroblasts may play an important role in the pathogenesis and development of
      CCh.

PMID- 28503428
TI  - Soluble expression of recomb inant cMyc, Klf4, Oct4, and Sox2 proteins in
      bacteria and transduction into living cells.
AB  - AIM: To develop a new method to produce recombinant reprogramming proteins, cMyc,
      Klf4, Oct4, and Sox2, in soluble format with low cost for the generation of
      induced pluripotent stem cells (iPSCs). METHODS: A short polypeptide sequence
      derived from the HIV trans-activator of transcription protein (TAT) and the
      nucleus localization signal (NLS) polypeptide were fused to the N terminus of the
      reprogramming proteins and they were constructed into pCold-SUMO vector which can
      extremely improve the solubility of recombinant proteins. Then these vector
      plasmids were transformed into E. coli BL21 (DE3) Chaperone competent cells for
      amplification. The solubility of these recombinant proteins was determined by SDS
      PAGE and Coomassie brilliant blue staining. The recombinant proteins were
      purified by Ni-NTA resin and identified by Western blot. The transduction of
      these proteins into HEK 293T cells were evaluated by immunofluorescence staining.
      RESULTS: These four reprogramming proteins could be produced in soluble format in
      pCold-SUMO expression vector system with the assistance of chaperone proteins in
      bacteria. The proteins were purified successfully with a purity of over 70% with
      a relative high transduction rate into 293 cells. CONCLUSION: The results in the
      present study indicate the four important reprogramming proteins, cMyc, Klf4,
      Oct4, and Sox2, can be produced in soluble format in bacteria with low cost. Our
      new method thus might be expected to greatly contribute to the future study of
      iPSCs.

PMID- 28503429
TI  - Suitability of open-field autorefractors as pupillometers and instrument design
      effects.
AB  - AIM: To determine the agreement and repeatability of the pupil measurement
      obtained with VIP-200 (Neuroptics), PowerRef II (Plusoptix), WAM-5500 (Grand
      Seiko) and study the effects of instrument design on pupillometry. METHODS: Forty
      patients were measured twice in low, mid and high mesopic. Repeatability was
      analyzed with the within-subject standard deviation (Sw) and paired t-tests.
      Agreement was studied with Bland-Altman plots and repeated measures ANOVA.
      Instrument design analysis consisted on measuring pupil size with PowerRef II
      simulating monocular and binocular conditions as well as with proximity cues and
      without proximity cues. RESULTS: The mean difference (+/-standard deviation)
      between test-retest for low, mid and high mesopic conditions were, respectively: 
      0.09 (+/-0.16), -0.05 (+/-0.18) and -0.08 (+/-0.23) mm for Neuroptics, -0.05 (+/
      0.17), -0.12 (+/-0.23) and -0.17 (+/-0.34) mm for WAM-5500, -0.04 (+/-0.27), 
      0.13 (+/-0.37) and -0.11 (+/-0.28) mm for PowerRef II. Regarding agreement with
      Neuroptics, the mean difference for low, mid and high mesopic conditions were,
      respectively: -0.48 (+/-0.35), -0.83 (+/-0.52) and -0.38 (+/-0.56) mm for WAM
      5500, -0.28 (+/-0.56), -0.70 (+/-0.55) and -0.61 (+/-0.54) mm for PowerRef II.
      The mean difference of binocular minus monocular pupil measurements was: -0.83
      (+/-0.87) mm; and with proximity cues minus without proximity cues was: -0.30 (+/
      0.77) mm. CONCLUSION: All the instruments show similar repeat-ability. In all
      illumination conditions, agreement of Neuroptics with WAM-5500 and PowerRef II is
      not good enough, which can be partially induced due to their open field design.

PMID- 28503430
TI  - Long-term rotational stability and visual outcomes of a single-piece hydrophilic
      acrylic toric IOL: a 1.5-year follow-up.
AB  - AIM: To evaluate the rotational stability and visual outcomes of a single-piece
      hydrophilic acrylic toric intraocular lenses (IOL) over a 1.5-year follow-up
      period. Data from the 6-month follow-up study have been previously reported.
      METHODS: Forty eyes of 26 cataract patients (mean age: 72.8+/-7.9y) with pre
      existing corneal astigmatism of 1.0 to 2.6 D were enrolled in the study. Mean
      axial length was 23.17+/-0.88 mm. Main outcome measures after implantation of the
      Torica-aA IOL (HumanOptics) were IOL rotational stability, subjective refraction,
      astigmatism correction, uncorrected and corrected distance visual acuity (UDVA,
      CDVA). RESULTS: There was no significant change in the parameters evaluated
      between the 6-month and 1.5-year follow-ups. At last visit, mean absolute IOL
      rotation (objective method) was 1.81 degrees +/-1.87 degrees  (range 0.00 degrees
      to 7.20 degrees ) with 78.6% of eyes having IOL rotation <3 degrees , 92.9% of
      eyes <5 degrees  and 100% of eyes <8 degrees . No patient required secondary IOL
      repositioning during the course of the study. Mean residual refractive cylinder
      was -0.60+/-0.40 D. There was a significant reduction in the magnitude of the J0
      vector postoperatively (P<0.0001) with a mean absolute change of 0.76+/-0.40 D.
      The mean J45 vector was close to zero preoperatively and postoperatively and
      didn't change significantly (P=0.28). Mean monocular UDVA and CDVA was 0.09+/
      0.12 logMAR and -0.01+/-0.12 logMAR, respectively. No treatment with Nd:YAG laser
      was required. CONCLUSION: The Torica-aA IOL shows good and stable visual
      performance and rotational stability over a 1.5-year follow-up period.

PMID- 28503431
TI  - A pilot study of intraocular lens explantation in 69 eyes in Chinese patients.
AB  - AIM: To study the effects of intraocular lens (IOL) explantation and demographic
      characteristics. METHODS: Retrospective non-comparative case series. Clinical
      data recorded from patient charts included the following: demographic,
      preoperative and postoperative characteristics; complications; surgical methods,
      and changes in visual acuity. RESULTS: A total of 69 eyes in 67 Chinese patients
      who received IOL explants were studied. The patients' mean age at the time of
      explantation was 46.1 years old [SD 22.5 (6-85)], and 37 patients were female
      (55.2%). Regarding employment, 47.8% were farmers, 23.9% were retired, 16.4% were
      students, 4.5% were unemployed, 3% were workers, and 4.5% were other (including
      staff members, teachers and officers). The main reasons for explantation were
      dislocation/decentration in 41 cases (59.4%) and retinal detachment in 10 cases
      (14.5%). The third most prevalent cause was incorrect lens power in 7 eyes
      (10.1%). The remaining reasons were endophthalmitis in 6 cases (8.7%), posterior
      capsular opacity in 3 eyes (4.3%), and impacting retinal surgery operation in 2
      cases (2.9%). The main comorbidities were high myopia in 18 eyes (26.1%), trauma
      in 8 eyes (11.6%), retinal detachment in 6 eyes (8.7%), congenital cataracts in 8
      eyes (11.6%), and Marfan's syndrome in 2 eyes (2.9%). The mean time from
      implantation to explantation was 4.0y [SD 4.2 (0.005-15)]. Treatment after
      explantation included posterior chamber IOL implantation in 44 eyes (63.8%) and
      aphakia in 25 eyes (36.2%). After surgery, the best corrected visual ability
      (BCVA) was improved in 50 cases (72.5%), including 28 patients (40.6%) in whom
      visual ability was improved by more than two lines. CONCLUSION:
      Dislocation/decentration is the main cause for explantation, and high myopia is a
      main risk factor. Posterior chamber IOL implantation remains the most elected
      treatment after explantation.

PMID- 28503432
TI  - Nutrient patterns and risk of cataract: a case-control study.
AB  - AIM: To assess the relation between nutrient patterns and cataract risk. METHODS:
      This is a hospital-based case-control study with 97 cataract patients and 198
      matched controls. Dietary consumption was collected through a valid food
      frequency questionnaire (FFQ). Nutrient patterns were detected by applying factor
      analysis. Unconditional logistic regression models were used to estimate odds
      ratio (ORs) and 95%CIs. RESULTS: We extracted 5 main nutrient patterns. Factor 1
      included niacin, thiamin, carbohydrates, protein, zinc, vitamin B6 and sodium
      (sodium pattern). Factor 2 was characterized by oleic acid, monounsaturated fats,
      polyunsaturated fats, linoleic acid, trans fatty acid, linolenic acid, vitamin E
      and saturated fats (fatty acid pattern). The third factor represented high intake
      of vitamin B12, vitamin D, cholesterol and calcium (mixed pattern). The 4th
      pattern was high in intake of beta and alpha carotene, vitamin A and vitamin C
      (antioxidant pattern). Finally, the 5th pattern loaded heavily on docosahexaenoic
      acid (DHA) and eicosapentaenoic acid (EPA) (omega-3 pattern). In crude and
      multivariate analysis, the sodium pattern was associated with increased risk of
      cataract (OR=1.97, 95%CI: 1.09-3.96). The fatty acid pattern elevated the risk of
      cataract (OR=1.94, 95%CI: 1.1-3.86). Antioxidant pattern was associated with a
      significant 79% reduced risk (2nd category compared with the 1st). Omega-3
      pattern was significantly negatively associated with risk of cataract (P=0.04).
      CONCLUSION: These findings imply that nutrient patterns reflecting a combined
      consumption of nutrients might be important in the etiology of cataract.
      Additional studies with more efficient designs are warranted to confirm our
      findings.

PMID- 28503433
TI  - Selective laser trabeculoplasty in pseudophakic and phakic eyes: a prospective
      study.
AB  - AIM: To compare the efficacy of selective laser trabeculoplasty (SLT) in
      replacing medical therapy in pseudophakic and phakic eyes. METHODS: Subgroup of a
      prospective randomized clinical trial including patients with primary open angle
      glaucoma or ocular hypertension controlled with medication. Of 38 pseudophakic
      eyes were matched with 38 phakic eyes. SLT was offered as a way to decrease
      medication while maintaining the same low eye pressure. SLT was performed over
      360 degrees , at 3ns, spotsize 400 um, 100 spots. Data [intraocular pressure
      (IOP), number of medications needed] were measured at 1h, 1wk, 1, 3, 6 and 12mo.
      An independent-samples t-test was performed to compare baseline characteristics
      of the phakic and the pseudophakic group and differences in evolution of mean IOP
      and number of used medications. Chi-squared analysis was performed to investigate
      proportions of fast, slow and non-responders. RESULTS: The mean IOP measurement
      was 13.00+/- 2.88 mm Hg in the phakic group (38 eyes) and 13.51+/-3.06 mm Hg in
      the pseudophakic group (38 eyes) (P>0.05). This changed little after SLT and IOP
      lowering effect was comparable between the two groups. Main aim however was to
      lower the amount of medication needed. In the phakic group medication lowered
      from 1.29+/-0.62 at baseline, to 0.15+/-0.46 after 12mo; a reduction of 88.37%.
      In the pseudophakic group, used medication changed from 1.71+/-1.04, to 0.41+/
      0.61; a 76.02% reduction. The differences were not statistically significant at
      any time point (P>0.05). IOP lowering occurred slightly faster in the
      pseudophakic group (50% of patients after one week) than in the phakic group (68%
      of patients after more than 4wk). The difference was not significant (P>0.05).
      CONCLUSION: IOP lowering effect of SLT is comparable between phakic and
      pseudophakic eyes.

PMID- 28503434
TI  - Comparison of isolated-check visual evoked potential and standard automated
      perimetry in early glaucoma and high-risk ocular hypertension.
AB  - AIM: To compare the diagnostic performance of isolated-check visual evoked
      potential (icVEP) and standard automated perimetry (SAP), for evaluating the
      application values of icVEP in the detection of early glaucoma. METHODS: Totally
      144 subjects (288 eyes) were enrolled in this study. icVEP testing was performed
      with the Neucodia visual electrophysiological diagnostic system. A 15% positive
      contrast (bright) condition pattern was used in this device to differentiate
      between glaucoma patients and healthy control subjects. Signal-to-noise ratios
      (SNR) were derived based on a multivariate statistic. The eyes were judged as
      abnormal if the test yielded an SNR<=1. SAP testing was performed with the
      Humphrey Field Analyzer II. The visual fields were deemed as abnormality if the
      glaucoma hemifield test results outside normal limits; or the pattern standard
      deviation with P<0.05; or the cluster of three or more non-edge points on the
      pattern deviation plot in a single hemifield with P<0.05, one of which must have
      a P<0.01. Disc photographs were graded as either glaucomatous optic neuropathy or
      normal by two experts who were masked to all other patient information.
      Moorfields regression analysis (MRA) used as a separate diagnostic classification
      was performed by Heidelberg retina tomograph (HRT). RESULTS: When the disc
      photograph grader was used as diagnostic standard, the sensitivity for SAP and
      icVEP was 32.3% and 38.5% respectively and specificity was 82.3% and 77.8%
      respectively. When the MRA Classifier was used as the diagnostic standard, the
      sensitivity for SAP and icVEP was 48.6% and 51.4% respectively and specificity
      was 84.1% and 78.0% respectively. When the combined structural assessment was
      used as the diagnostic standard, the sensitivity for SAP and icVEP was 59.2% and
      53.1% respectively and specificity was 84.2% and 84.6% respectivlely. There was
      no statistical significance between the sensitivity or specificity of SAP and
      icVEP, regardless of which diagnostic standard was based on. CONCLUSION: The
      diagnostic performance of icVEP is not better than that of SAP in the detection
      of early glaucoma.

PMID- 28503435
TI  - Evaluation of hyperreflective foci as a prognostic factor of visual outcome in
      retinal vein occlusion.
AB  - AIM: To evaluate the potential role of hyperreflective foci (HF) as a prognostic
      indicator of visual outcome in patients with macular edema (ME) due to retinal
      vein occlusion (RVO). METHODS: We retrospectively reviewed 50 eyes of 50 patients
      with ME due to ischemic central retinal vein occlusion (CRVO), non-ischemic CRVO
      and branch retinal vein occlusion (BRVO) who were treated with anti-vascular
      endothelial growth factor (anti-VEGF) at Beijing Tongren Eye Center from January
      2013 to July 2016. All patients underwent best-corrected visual acuity (BCVA),
      spectral domain optical coherence tomography (SD-OCT) at baseline and follow-up.
      Such factors were evaluated and compared among three groups as baseline and final
      BCVA, central retinal thickness (CRT), external limiting membrane (ELM) status
      and the numbers of HF in different position. Multiple linear regression analysis
      was employed to analyze the relationship between baseline HF and final BCVA.
      Changes of HF before and after treatment were evaluated too. RESULTS: Among three
      groups, HF could be located in each retinal layers, as well as in vitreous
      cavity. The mean HF in outer retinal layer (ORL) at baseline was 5.29+/-8.48 in
      ischemic CRVO with intact ELM, 1.93+/-2.76 in non-ischemic CRVO, and 1.75+/-2.05
      in BRVO. With disrupted ELM, the mean HF in ORL increased. There was
      statistically difference of HF in ORL between intact and disrupted ELM. The
      numbers of HF in ORL were associated with poor visual outcome among three groups.
      However, HF in inner retinal layer (IRL) and vitreous cavity were not associated
      with poor visual outcome. Meanwhile, the baseline HF in ORL and vitreous cavity
      reduced significantly in non-ischemic CRVO and BRVO after anti-VEGF treatment.
      CONCLUSION: The numbers of HF in ORL are prognostic factors associated with the
      final BCVA in patients with ME due to RVO after anti-VEGF treatment.

PMID- 28503437
TI  - Comparison of postoperative optical quality according to the degree of
      decentering of V4c implantable collamer lens.
AB  - AIM: To evaluate the clinical outcomes of V4c implantable collamer lens (Hole
      ICL) implantation with regard to the optical quality assessed according to
      different degrees of decentering. METHODS: This included 49 eyes that received
      conventional ICL and 94 eyes that received Hole ICL. The eyes that received Hole
      ICL were divided into three groups according to the degree of decentering: group
      1, central hole within 1 hole diameter (HD) from the pupil center; group 2,
      central hole within 1 HD to 2 HD; and group 3, central hole within 2 HD to 3 HD.
      Visual acuity (VA), intraocular pressure (IOP), and spherical equivalent (SE)
      values were assessed at 1wk, 1 and 3mo after surgery. The ocular modulation
      transfer function, Strehl ratio, objective scattering index, and higher order
      aberrations (HOAs) were measured for 4-mm pupils at 3mo after surgery. RESULTS:
      There were no significant differences in VA, IOP, and SE among the conventional
      and Hole ICL groups. With regard to HOAs, values for coma and spherical
      aberrations showed no differences. The total HOA and trefoil values were
      significantly higher in group 2 than in group 1 (P=0.02, 0.03, respectively).
      There were no significant differences among groups with regard to other optical
      quality parameter at 3mo after surgery. CONCLUSION: Our results suggest that Hole
      ICL implantation provides satisfactory visual quality that is equivalent to that
      provided by conventional ICL, regardless of the presence of central hole and
      degree of decentering.

PMID- 28503436
TI  - Association of choroidal thickness with early stages of diabetic retinopathy in
      type 2 diabetes.
AB  - AIM: To assess the correlation between choroidal thickness (CT) and the early
      stages of diabetic retinopathy (DR) in type 2 diabetic patients. METHODS: We
      divided 83 diabetic patients (51-80 years of age; 50 females) into non diabetic
      retinopathy group (NDR) and mild/moderate nonproliferative diabetic retinopathy
      (NPDR) group, and compared them with 26 non-diabetic control subjects (51-78
      years of age; 16 females). Subfoveal choroidal thickness (SFCT) and parafoveal
      choroidal thickness (PFCT) were measured using enhanced depth imaging spectral
      domain optical coherence tomography (EDI-OCT). Ocular health status, disease
      duration, body mass index, and hemoglobin A1c (HbA1c) were recorded. RESULTS: The
      mean ages of the NDR, NPDR, and control groups were 68.0+/-6.9y, 67.8+/-6.4y, and
      65.1+/-6.3y, respectively (P=0.17). Pearson correlation of the right and left
      eyes for the control subjects was 0.95 and for the NDR subjects was 0.93. SFCT
      for the right eyes of the controls was 252.77+/- 41.10 um, which was
      significantly thicker than that of the right eyes in NDR group (221.51+/-46.56
      um) and the worse eyes of the NPDR group (207.18+/-61.87 um; ANOVA, P<0.01). In
      the diabetic patients pooled together, age was the only variable significantly
      associated with SFCT (multiple linear regression analysis, P=0.01). CONCLUSION:
      CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with
      the control eyes. Age is significantly associated with SFCT in the diabetic
      patients. Diabetic choroidopathy may be present before clinical retinopathy.

PMID- 28503438
TI  - Comparison of visual effects of FS-LASIK for myopia centered on the coaxially
      sighted corneal light reflex or the line of sight.
AB  - AIM: To compare visual quality after femtosecond laser in situ keratomileusis (FS
      LASIK), between the coaxially sighted corneal light reflex (CSCLR) group and
      conventional ablation line of sight (LOS) group. METHODS: In total, 243 eyes (122
      patients) were treated with centration on the CSCLR (visual axis) and 238 eyes
      (119 patients) treated with centration on the pupil center (LOS). Postoperative
      outcomes [uncorrected visual acuity (UCVA), best spectacle-corrected visual
      acuity (BSCVA)], safety index, efficacy index, refractive outcome, ablation
      center distance from the visual axis, corneal high-order aberrations, subjective
      discomfort glare and shadowing incidence rate, and contrast sensitivity at 1, 3,
      and 6mo were measured and compared. RESULTS: The mean age was 27.77+/-7.1y in the
      CSCLR group and 26.03+/-7.70y in the LOS group. Preoperatively, the manifest
      refraction spherical equivalent (MRSE) was -6.68+/-2.60 D in the CSCLR group and 
      6.65+/-2.68 D in the LOS group. The postoperative UCVA, BSCVA, MRSE (-0.03+/
      0.263 D in the CSCLR group, -0.05+/-0.265 D in the LOS group), efficacy index
      (1.04, 1.03), and safety index (1.09, 1.08) were not significantly different
      between the groups (all P>0.05). In total, 3% lost one line and more of BSCVA in
      the CSCLR group, as 9% in the LOS group postoperatively (P<0.05). The ablation
      center deviation was 0.20+/-0.15 mm from the visual axis (Pentacam system default
      setting; range, 0-0.75 mm) in the CSCLR group, and 0.43+/-0.22 mm (range, 0-1.32
      mm) in the LOS group (P<0.0001). Statistically significant greater augmentation
      of total corneal higher-order aberrations (0.15+/-0.10 um and 0.20+/-0.12 um
      respectively, P=0.03) and vertical and horizontal coma (P<0.0001) were noted in
      the LOS group. Subjective discomfort glare and shadowing incidence rates were
      8.59% and 17.5% in the CSCLR and LOS groups, respectively (P<0.05). The 1-month
      postoperative contrast sensitivity visual acuity in the CSCLR group was
      significantly higher than that in the LOS group on contrast (100%, 25%, 10%) with
      a dark background, but there was no significant difference between the groups at
      3 or 6m. CONCLUSION: Myopic LASIK centered on the CSCLR achieves significantly
      lower induction of loss of BSCVA, corneal high-order aberrations, and lower risk
      of subjective discomfort glare and shadowing, and lower decline in early contrast
      sensitivity by comparison with centration on the LOS, giving advantages in visual
      quality postoperatively.

PMID- 28503439
TI  - Dry eye and corneal sensitivity after small incision lenticule extraction and
      femtosecond laser-assisted in situ keratomileusis: a Meta-analysis.
AB  - AIM: To assess the corneal sensitivity and the incidences of dry eye after small
      incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ
      keratomileusis (FS-LASIK). METHODS: The Meta-analysis was performed using RevMan
      5.3. We searched on PubMed from inception to March 2016. Summary weighted mean
      difference (WMD) and 95% confidence intervals (CIs) were used to analyze the
      datum. Random-effects or fixed-effects models were chosen up to between-study
      heterogeneity. The main outcomes were composed of the Ocular Surface Disease
      Index (OSDI) scores, tear film break-up time (TBUT), Schirmer Test and corneal
      sensitivity. RESULTS: Eight eligible studies including 772 eyes (386 in SMILE
      group and 386 in FS-LASIK group) were identified. The parameters have no
      significiant difference heterogeneity between SMILE and FS-LASIK group
      preoperatively. There were significant differences between the two groups in OSDI
      scores at one and three months postoperatively, in TBUT at one and three months
      postoperatively, in corneal sensitivity at one week, about one month and three
      months postoperatively. However, there was no significant difference observed in
      Schirmer Test at the follow-up periods. CONCLUSION: Compare to FS-LASIK, dry eye
      and the corneal sensitivity recover better in the SMILE group, in first three
      months after the surgery.

PMID- 28503440
TI  - MnSOD Val16Ala polymorphism associated with retinopathy risk in diabetes: a
      PRISMA-compliant Meta-analysis of case-control studies.
AB  - AIM: To investigate the association of Manganese superoxide dismutase (MnSOD)
      Val16Ala polymorphism with diabetic retinopathy (DR). METHODS: PubMed, Embase,
      China National Knowledge Infrastructure, and Wanfang databases were searched. The
      pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to
      evaluate the strength of the association. Subgroup, sensitivity, and cumulative
      analyses were performed. Publication bias was also analyzed. RESULTS: Eight
      studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was
      associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48
      0.91, P<0.0001), this result was demonstrated to be relatively stable in
      cumulative analysis. No significant publication bias was found. This polymorphism
      was also associated with the risk of DR in Caucasians under the dominant model
      (OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model
      (OR=0.31, 95%CI=0.11-0.88, P=0.03). CONCLUSION: These findings suggest that the
      MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention
      should be paid to carriers of these susceptibility genes.

PMID- 28503441
TI  - Applications of CRISPR/Cas9 in retinal degenerative diseases.
AB  - Gene therapy is a potentially effective treatment for retinal degenerative
      diseases. Clustered regularly interspaced short palindromic repeats
      (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new
      genome-editing tool in ophthalmic studies. Recent advances in researches showed
      that CRISPR/Cas9 has been applied in generating animal models as well as gene
      therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis
      (LCA). It has also been shown as a potential attempt for clinic by combining with
      other technologies such as adeno-associated virus (AAV) and induced pluripotent
      stem cells (iPSCs). In this review, we highlight the main points of further
      prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also
      emphasize the potential applications of this technique in treating retinal
      degenerative diseases.

PMID- 28503443
TI  - Vascular anomaly in the levator aponeurosis of neurofibromatosis type 1.

PMID- 28503442
TI  - Clinical outcomes at one year following keratoconus treatment with accelerated
      transepithelial cross-linking.
AB  - This study evaluated the clinical outcomes in keratoconus corneas following
      accelerated transepithelial corneal collagen cross-linking (CXL) (Avedro KXL(r)
      system, Waltham, MA, USA) over one year of follow-up. The mean depth of the
      demarcation line measured by optical coherence tomography (OCT) was 205.19 um.
      One month after surgery, a non-statistically significant change was noted in
      sphere (P=0.18) and in spherical equivalent (P=0.17), whereas a significant
      improvement was observed in corrected distance visual acuity (P=0.04). A
      significant change was observed in topographic astigmatism (P=0.03) and posterior
      corneal a sphericity (P=0.04). Accelerated transepithelial CXL may be a useful
      technique for the management of progressive keratoconus.

PMID- 28503444
TI  - Keratoconus associated with Williams-Beuren syndrome: a new case report.

PMID- 28503445
TI  - Optical coherence tomography angiography in incomplete acute Vogt-Koyanagi-Harada
      disease.

PMID- 28503446
TI  - Comment on hydration with Cefuroxime-a method for sealing a small leaking corneal
      perforation.

PMID- 28503447
TI  - Strengthening Health Systems to Provide Rehabilitation Services.

PMID- 28503448
TI  - Resting-State Metabolism of Hand Knob Area on 18F-FDG PET-CT According to Hand
      Function and Tractography of Corticospinal Tract After Stroke.
AB  - OBJECTIVE: To correlate the resting metabolism of hand knob and hand function
      after stroke, diffuse tensor tractography (DTT) and 18F-fluorodeoxyglucose
      position emission tomography (18F-FDG PET) were used to evaluate constructible
      state of white matter tract and metabolic state of gray matter, respectively.
      METHODS: A total of 17 patients were included in the study, who had suffered a
      stroke with hand weakness, after a stroke. They underwent diffusion tensor
      analysis and FDG PET in the subacute period. The ratio of both hemisphere
      parameters in voxel number of fibers, fractional anisotropy (FA) and apparent
      diffusion coefficient obtained by corticospinal tract as constructed by DTT, and
      the metabolism of hand knob area on cerebral cortex obtained from 18F-FDG PET
      were calculated. Hand movement scale was evaluated on the day of FDG PET or
      tractography, and at 6 months after onset. RESULTS: Difference of FA in DTT
      between both hemispheres and hand knob metabolism in FDG PET significantly
      correlated with the hand movement scale at the subacute stage and 6 months after
      onset. However, the difference of both hemispheres in DTT and metabolism of hand
      knob area was not significant. CONCLUSION: Resting metabolism on hand knob in FDG
      PET correlated with hand function after stroke.

PMID- 28503449
TI  - Feasibility of Rehabilitation Training With a Newly Developed, Portable, Gait
      Assistive Robot for Balance Function in Hemiplegic Patients.
AB  - OBJECTIVE: To investigate the clinical feasibility of a newly developed,
      portable, gait assistive robot (WA-H, 'walking assist for hemiplegia') for
      improving the balance function of patients with stroke-induced hemiplegia.
      METHODS: Thirteen patients underwent 12 weeks of gait training on the treadmill
      while wearing WA-H for 30 minutes per day, 4 days a week. Patients' balance
      function was evaluated by the Berg Balance Scale (BBS), Fugl-Meyer Assessment
      Scale (FMAS), Timed Up and Go Test (TUGT), and Short Physical Performance Battery
      (SPPB) before and after 6 and 12 weeks of training. RESULTS: There were no
      serious complications or clinical difficulties during gait training with WA-H. In
      three categories of BBS, TUGT, and the balance scale of SPPB, there was a
      statistically significant improvement at the 6th week and 12th week of gait
      training with WA-H. In the subscale of balance function of FMAS, there was
      statistically significant improvement only at the 12th week. CONCLUSION: Gait
      training using WA-H demonstrated a beneficial effect on balance function in
      patients with hemiplegia without a safety issue.

PMID- 28503450
TI  - Balance Assessment in Subacute Stroke Patients Using the Balance Control Trainer
      (BalPro).
AB  - OBJECTIVE: To demonstrate the efficacy of the balance control trainer (BCT),
      developed for training patients with balance problems, as a balance assessment
      tool in subacute stroke patients. METHODS: A prospective cross-sectional study
      was carried out on 38 subacute stroke patients in their first episode of a
      stroke, and having the ability to maintain a standing position without aid for at
      least 5 minutes. Patients were assessed using the BCT (BalPro) 43.7+/-35.7 days
      after stroke. The balance was assessed using the Berg Balance Scale (BBS), the
      Timed Up and Go Test (TUG), a 10-meter walking test (10mWT), a 6-minute walking
      test (6MWT), and the Korean version of the Modified Barthel Index. The
      correlation and validity between the BCT and various balance assessments were
      analyzed. RESULTS: Statistically significant linear correlations were observed
      between the BCT score and the BBS (r=0.698, p<0.001). A moderate to excellent
      correlation was seen between the BCT score and 11 of the 14 BBS items. The BCT
      scores and other secondary outcome parameters (6MWT r=0.392, p=0.048; TUG r=
      0.471, p=0.006; 10mWT r=-0.437, p=0.012) had a moderate correlation. CONCLUSION:
      Balance control training using the BCT (BalPro) showed significant statistical
      correlation with the BBS, and could therefore be a useful additional balance
      assessment tool in subacute stroke patients.

PMID- 28503451
TI  - Association Between a Polymorphism in CASP3 and CASP9 Genes and Ischemic Stroke.
AB  - OBJECTIVE: To investigate whether the polymorphisms of CASP3 gene (rs4647602,
      intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and
      rs1052571, Ser/Val T/C) were associated with the development, and clinical
      severity of ischemic stroke and functional consequences after stroke. METHODS:
      Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects
      were extracted, and polymerase chain reaction products were sequenced. To
      investigate the association of polymorphisms and the development, and National
      Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were
      analyzed. RESULTS: Polymorphism of the untranslational region of CASP3
      (rs1049216, UTR C/T) has been associated with the development of ischemic stroke
      in codominant1 model (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.29
      0.88; p=0.017), in dominant model (OR, 0.57; 95% CI, 0.34-0.97; p=0.034), and in
      the overdominant model (OR, 0.50; 95% CI, 0.29-0.87; p=0.011). A missense SNP of
      CASP9 gene (rs1052571, Ser/Val T/C) was associated with the development of
      ischemic stroke (OR, 1.93; 95% CI, 1.05-3.55; p=0.034 in recessive model).
      CONCLUSION: These results indicate the possibility that CASP3 and CASP9 genes are
      markers for the development of ischemic stroke.

PMID- 28503452
TI  - Relation of Urinary Retention and Functional Recovery in Stroke Patients During
      Rehabilitation Program.
AB  - OBJECTIVE: To investigate the relationship between urinary retention and short
      term functional recovery in subacute stage after stroke. METHODS: The medical
      records of 94 patients admitted to the rehabilitation unit of Korea University
      Guro Hospital were reviewed retrospectively. The postvoid residual urine (PVR)
      was measured at least once a day using a bladder scan, and urinary retention (UR)
      was defined when the daily PVR volume consistently checked more than 100 mL.
      Clinical data and functional outcomes of patients in the rehabilitation ward were
      collected. Functional outcomes were measured using the Mini-Mental State
      Examination (MMSE), Berg Balance Scale (BBS), Functional Ambulation Category
      (FAC) level, Fugl-Meyer Assessment (FMA), and Modified Barthel Index (MBI) at
      admission (or transfer) and discharge. The data of patients with and without
      urinary retention were compared and analyzed. RESULTS: Of the 94 participants, 25
      patients were classified to the UR group and 69 were classified to the non-UR
      group. At the initial stage of rehabilitation, the scores of MMSE, BBS, FAC, MBI
      were significantly worse in the UR group (p<0.05). Both groups showed significant
      improvements of all functional outcomes after rehabilitation (p<0.05). The non-UR
      group showed more prominent recovery of BBS, FAC, MBI scores (p<0.05).
      CONCLUSION: Urinary retention in post-stroke patients is significantly related to
      the poor functional status at initial stage of rehabilitation, and also to poor
      recovery after rehabilitation.

PMID- 28503453
TI  - Relationship Between Motor Evoked Potential Response and the Severity of
      Paralysis in Spinal Cord Injury Patients.
AB  - OBJECTIVE: To investigate the relationship between motor evoked potential (MEP)
      response and the severity of motor paralysis, evaluated according to the Korean
      disability evaluation system in patients with spinal cord injury (SCI). METHODS:
      We analyzed 192 lower limbs of 96 SCI patients. Lower limbs were classified
      according to their motor scores, as determined by the International Standards for
      Neurological Classification of Spinal Cord Injury: motor score <10 (group 1);
      >=10 and <15 (group 2); >=15 and <20 (group 3); and >=20 (group 4). MEP responses
      were classified as 'normal', 'delayed' or 'absent', based on their onset latency,
      which was compared between the different motor score groups. RESULTS: MEP
      responses and limb motor scores were highly correlated (p<0.001). There was a
      significant difference of MEP responses between the motor score groups (p<0.001).
      MEP response was markedly poorer in motor group 1 (limb motor score <10) than in
      the other three groups (p<0.0001). However, there were no differences between the
      three groups with motor scores of 10 or above. CONCLUSION: Clinical utility of
      MEP as a complimentary tool to manual muscle tests could be limited to
      discriminating motor score groups with severe paralysis, i.e., single lower limb
      motor power grades of 0 or 1, and from grade 2, 3, and 4, or above, in the Korean
      disability evaluation system.

PMID- 28503454
TI  - Quantitative Assessment of Proprioception Using Dynamometer in Incomplete Spinal
      Cord Injury Patients: A Preliminary Study.
AB  - OBJECTIVE: To investigate the feasibility of a knee proprioception evaluation
      using a dynamometer as a tool for evaluating proprioception of the lower
      extremities in patients with incomplete spinal cord injury (SCI), and to explore
      its usefulness in predicting the ambulatory outcome. METHODS: A total of 14 SCI
      patients (10 tetraplegic, 4 paraplegic; all AIS D) were included in this study.
      The passive repositioning error (PRE) and active repositioning error (ARE) were
      measured with a dynamometer, along with tibial somatosensory evoked potential
      (SSEP) and abductor hallucis motor-evoked potential (MEP). Ambulatory capacity
      was assessed with the Walking Index for Spinal Cord Injury II (WISCI-II), both at
      the time of the proprioception test (WISCI_i) and at least 6 months after the
      test (WISCI_6mo). RESULTS: The PRE showed a negative correlation with WISCI_i (r=
      0.440, p=0.034) and WISCI_6mo (r=-0.568, p=0.010). Linear multiple regression
      showed the type of injury, lower extremities motor score, MEP, and PRE accounted
      for 75.4% of the WISCI_6mo variance (p=0.080). CONCLUSION: Proprioception of the
      knee can be measured quantitatively with a dynamometer in patients with
      incomplete SCI, and PRE was related to the outcome of the ambulatory capacity.
      Along with the neurological and electrophysiological examinations, a
      proprioception test using a dynamometer may have supplementary value in
      predicting the ambulatory capacity in patients with incomplete SCI.

PMID- 28503455
TI  - Lesion Characteristics of Chronic Dysphagia in Patients With Supratentorial
      Stroke.
AB  - OBJECTIVE: To analyze the relationship between brain lesion location and type of
      chronic dysphagia in patients with supratentorial stroke. METHODS: Data from 82
      chronic stroke patients who underwent videofluoroscopic swallowing studies at >6
      months after an initial stroke event were retrospectively analyzed. Delayed oral
      transit time, delayed pharyngeal transit time, and the presence of aspiration
      were extracted. A voxel-based lesion symptom mapping (VLSM) analysis was used to
      correlate types of dysphagia with specific brain lesions. RESULTS: VLSM
      identified several clusters of voxels that significantly correlated with type of
      dysphagia. Delayed oral transit time mainly correlated with lesions in the left
      inferior frontal lobe and precentral gyrus; delayed pharyngeal time mainly
      correlated with lesions in the right basal ganglia and corona radiate; and
      aspiration was mainly correlated with lesions in the putamen. CONCLUSION:
      Understanding the association between lesion location and dysphagia in chronic
      stroke patients is an important first step towards predicting permanent dysphagia
      after stroke. Improved understanding of the neural correlates of dysphagia will
      inform the utility of interventions for its treatment and prevention after
      stroke.

PMID- 28503456
TI  - Effect of Vallecular Ballooning in Stroke Patients With Dysphagia.
AB  - OBJECTIVE: To investigate the improvement of dysphagia after balloon dilatation
      and balloon swallowing at the vallecular space with a Foley catheter in stroke
      patients. METHODS: This study was conducted between May 1, 2012 and December 31,
      2015, and involved 30 stroke patients with complaints of difficulty in
      swallowing. All patients underwent videofluoroscopic swallowing study (VFSS)
      before and after vallecular ballooning. VFSS was performed with a 4 mL semisolid
      bolus. For vallecular ballooning, two trainings were performed for at least 10
      minutes, including backward stretching of the epiglottis and swallowing of a
      balloon located in the vallecular space, by checking the movement of the Foley
      catheter tip in real time using VFSS. RESULTS: After examination of the dysphagia
      improvement pattern before and after vallecular ballooning, laryngeal elevation
      (x-axis: pre 2.62+/-1.51 mm and post 3.54+/-1.93 mm, p=0.038; y-axis: pre 17.11+/
      4.24 mm and post 22.11+/-3.46 mm, p=0.036), pharyngeal transit time (pre 5.76+/
      6.61 s and post 4.08+/-5.49 s, p=0.043), rotation of the epiglottis (pre 53.24
      degrees +/-26.77 degrees  and post 32.45 degrees +/-24.60 degrees , p<0.001), and
      post-swallow pharyngeal remnant (pre 41.31%+/-23.77% and post 32.45%+/-24.60%,
      p=0.002) showed statistically significant differences. No significant difference
      was observed in the penetration-aspiration scale score (pre 4.73+/-1.50 and post
      4.46+/-1.78, p=0.391). CONCLUSION: For stroke patients with dysmotility of the
      epiglottis and post-swallowing residue, vallecular ballooning can be considered
      as an alternative method that can be applied without risk of aspiration in
      dysphagia treatment.

PMID- 28503457
TI  - The Association Between Fall History and Physical Performance Tests in the
      Community-Dwelling Elderly: A Cross-Sectional Analysis.
AB  - OBJECTIVE: To evaluate the association between baseline characteristics, three
      physical performance tests and fall history in a sample of the elderly from
      Korean population. METHODS: A total of 307 participants (mean age, 76.70+/-4.85
      years) were categorized into one of two groups, i.e., fallers and non-fallers.
      Fifty-two participants who had reported falling unexpectedly at least once in the
      previous 12 months were assigned to the fallers group. Physical performance tests
      included Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS),
      Timed Up and Go test. The differences between the two study groups were compared
      and we analyzed the correlations between fall histories and physical performance
      tests. RESULTS: SPPB demonstrated a significant association with fall history.
      Although the BBS total scores did not show statistical significance, two dynamic
      balance test items of BBS (B12 and B13) showed a significant association among
      fallers. CONCLUSION: This study suggests that SPPB and two dynamic balance test
      items of the BBS can be used in screening for risk of falls in an ambulatory
      elderly population.

PMID- 28503458
TI  - Quality of Life and Awareness of Cardiac Rehabilitation Program in People With
      Cardiovascular Diseases.
AB  - OBJECTIVE: To evaluate the level of health-related quality of life (HRQoL), life
      satisfaction, and their present awareness of cardiac rehabilitation (CR) program
      in people with cardiovascular diseases. METHODS: A questionnaire survey was
      completed by 53 patients (mean age, 65.7+/-11.6 years; 33 men and 20 women) with
      unstable angina, myocardial infarction, or heart failure. The questionnaire
      included the Medical Outcome Study 36-item Short-Form Health Survey (MOS SF-36),
      life domain satisfaction measure (LDSM), and the awareness and degree of using CR
      program. RESULTS: The average scores of physical component summary (PCS) and
      mental component summary (MCS) were 47.7+/-18.5 and 56.5+/-19.5, respectively.
      There were significant differences in physical role (F=4.2, p=0.02), vitality
      (F=10.7, p<0.001), mental health (F=15.9, p<0.001), PCS (F=3.6, p=0.034), and MCS
      (F=11.9, p<0.001) between disease types. The average LDSM score was 4.7+/-1.5.
      Age and disease duration were negatively correlated with multiple HRQoL areas
      (p<0.05). Monthly income, ejection fraction, and LDSM were positively correlated
      with several MOS SF-36 factors (p<0.05). However, the number of modifiable risk
      factors had no significant correlation with medication. Thirty-seven subjects
      (69.8%) answered that they had not previously heard about CR program. Seventeen
      patients (32.1%) reported that they were actively participating in CR program.
      Most people said that a reasonable cost of CR was less than 100,000 Korean won
      per month. CONCLUSION: CR should focus on improving the physical components of
      quality of life. In addition, physicians should actively promote CR to
      cardiovascular disease patients to expand the reach of CR program.

PMID- 28503459
TI  - Changes in Resting Calcaneal Stance Position Angle Following Insole Fitting in
      Children With Flexible Flatfoot.
AB  - OBJECTIVE: To clarify the relationship of the initial radiologic and a
      biomechanical parameter at first clinical visit, and define the effectiveness of
      modified insole, following insole fitting in children with flexible flatfoot.
      METHODS: Children aged less than 13 years with flexible flatfoot were enrolled.
      The total number of subjects was 66 (33 boys, 33 girls). The subjects were
      divided into 5 subgroups, based on age: 1-2, 3-4, 5-6, 7-9, and 10-12 years. The
      mean time period between the initial & final examination for their resting
      calcaneal stance position angle (RCSPA) was 24 months. Radiography quantified the
      deformity by measuring angles, including the talometatarsal angle, the metatarsal
      angle, and the calcaneal pitch angle. RESULTS: From the angles measured on
      radiographs, only the talometatarsal angle showed a statistically significant
      correlation to the initial RCSPA (r=-0.578 for right side, r=-0.524 for left
      side; p<0.01). The mean RCSPA improved in all subgroups of subjects following
      insole fitting. Moreover, in children younger than 7 years, the improvement in
      RCSPA from the insole fitting was greater compared to children aged 7 years and
      older. CONCLUSION: The insole has additionally beneficial effects in all
      populations younger than 13 years. However, there might exist a hidden effect of
      normal structural pedal alignment during growth accompanied with bony maturation
      and developmental process. To date, it is controversial whether the treatment of
      flexible flatfoot is necessary in the vast majority of cases, or simple
      observation and advice to parents would suffice.

PMID- 28503460
TI  - Relationship Between Mobility and Self-Care Activity in Children With Cerebral
      Palsy.
AB  - OBJECTIVE: To investigate the factors influencing the development of self-care
      activity, and the association between mobility and self-care activity in children
      with cerebral palsy (CP). METHODS: A total of 63 CP children aged >=4 years, were
      studied retrospectively. Children with severe intellectual disability or
      behavioral problems were excluded. The relationship between the Gross Motor
      Function Classification System (GMFCS), the Manual Ability Classification System
      (MACS), and the Pediatric Evaluation of Disability Inventory (PEDI) was analyzed.
      Simple and multiple linear regression analyses were conducted for continuous
      variables, such as verbal intelligence quotient (IQ) and PEDI subscales. RESULTS:
      Final evaluation was done for 25 children, ranging from 4 to 11 years of age.
      According to GMFCS levels, the differences in PEDI-self-care scores, showed
      statistically borderline significance (p=0.051). Conversely, differences in PEDI
      self-care scores according to CP types and MACS levels were not statistically
      significant. Simple linear regression analysis showed that PEDI mobility and PEDI
      social function significantly influence the PEDI self-care. Multiple linear
      regression analysis showed that PEDI mobility was the only factor significantly
      influencing PEDI self-care in children aged >=7 years (R2=0.875, p=0.03).
      CONCLUSION: Mobility is important for the acquisition of self-care abilities in
      children with CP aged >=7 years.

PMID- 28503461
TI  - Immediate Effect of a Single Session of Whole Body Vibration on Spasticity in
      Children With Cerebral Palsy.
AB  - OBJECTIVE: To investigate the immediate effect of a single session of whole body
      vibration (WBV) on lower extremity spasticity in children with cerebral palsy
      (CP). METHODS: Seventeen children with spastic CP were included. A single session
      of WBV was administered: 10-minute WBV, 1-minute rest, and 10-minute WBV. The
      effects of WBV were clinically assessed with the Modified Ashworth Scale (MAS)
      and Modified Tardieu Scale (MTS) before and immediately, 30 minutes, 1 hour, 2
      hours, 3 hours, and 4 hours after WBV. RESULTS: Spasticity of the ankle
      plantarflexor, as assessed by MAS and MTS scores, was reduced after WBV. Post-hoc
      analysis demonstrated that, compared to baseline, the MAS significantly improved
      for a period of 1 hour after WBV, and the R1 and R2-R1 of the MTS significantly
      improved for a period of 2 hours after WBV. CONCLUSION: A single session of WBV
      improves spasticity of ankle plantarflexors for 1-2 hours in children with CP.
      Future studies are needed to test whether WBV is an effective preparation before
      physiotherapy and occupational therapy.

PMID- 28503462
TI  - Predictors for Depressive Mood in Geriatric Patients After Traumatic Brain
      Injury: A Retrospective Cross-Sectional Study.
AB  - OBJECTIVE: To identify predictors for depressive mood in geriatric patients after
      traumatic brain injury (TBI). METHODS: A retrospective review of patients'
      medical charts was performed in TBI patients who were older than 60 years and
      referred to the Department of Rehabilitation Medicine at Severance Hospital in
      2002-2016. The patients were classified into two groups based on the Geriatric
      Depression Scale (GDS): non-depressive group (0<=GDS<=16) and depressive group
      (17<=GDS<=30). Data was collected on demographic, socioeconomic, comorbidities,
      and trauma-related factors, as well as the pathophysiology of TBI, localization
      of lesion, post-traumatic complications, functional level, and cognitive and
      linguistic function. Significant variables from univariate analysis were analyzed
      using logistic regression. RESULTS: Forty-two patients were included, of whom
      64.3% displayed a depressive mood. Patients in the depressive group had higher
      comorbidity scores (p=0.03), lower Functional Independence Measure (FIM) totals
      (p=0.03) and FIM motor (p=0.03) scores, higher modified Rankin Scale scores
      (p=0.04), and frequently had a bilateral or left side brain lesion (p=0.002).
      Higher comorbidity scores (odds ratio [OR], 1.764; 95% confidence interval [CI],
      1.047-2.971), bilateral lesions (OR, 13.078; 95% CI, 1.786-95.780), and left side
      lesions (OR, 46.074; 95% CI, 3.175-668.502) were independently associated with a
      depressive mood in the multiple logistic regression analysis. CONCLUSION: The
      risk of depressive mood in geriatric patients after TBI is associated with
      comorbidity, functional limitation, and the horizontal distribution of brain
      lesions. The most significant determining factors were comorbidity and the
      horizontal distribution of brain lesions. Early detection of risk factors is
      important to prevent and manage depressive mood in geriatric patients after TBI.

PMID- 28503463
TI  - Optimal Radial Motor Nerve Conduction Study Using Ultrasound in Healthy Adults.
AB  - OBJECTIVE: To obtain reference values, to suggest optimal recording and
      stimulation site for radial motor nerve conduction study (RmNCS), and to analyze
      the correlation among RmNCS parameters, demographics and ultrasonography (US)
      findings. METHODS: A total of 55 volunteers participated in this study. We
      hypothesized that 'lateral edge of spiral groove (A)' was the optimal stimulation
      site, and the 'largest cross-sectional area (CSA) of extensor indicis proprius
      (EIP) muscle (B)' was the optimal recording site. The surface distance between
      'A' and the lateral epicondyle of the humerus divided by upper arm length, was
      named the spiral groove ratio. The surface distance between 'B' and the ulnar
      styloid process divided by forearm length, was named the EIP ratio. Using US, we
      identified these sites, and further conducted RmNCS. RESULTS: Data was collected
      from 100 arms of the 55 volunteers. Mean amplitude and latency were 5.7+/-1.1 mV
      and 5.7+/-0.5 ms, respectively, at the spiral groove, and velocity between elbow
      and spiral groove was 73.7+/-7.0 m/s. RmNCS parameters correlated significantly
      with height, weight, arm length, and CSA of the EIP muscle. Spiral groove ratio
      and EIP ratio were 0.338+/-0.03 and 0.201+/-0.03, respectively; both values were
      almost the same, regardless of age, sex and handedness. CONCLUSION: We
      established a reference value and standardized method of RmNCS using US. Optimal
      RmNCS can be conducted by placing the recording electrode 20% (about one-fifth)
      of forearm length from the ulnar styloid process, and stimulating at 34% (about
      one-third) of the humeral length from the lateral epicondyle.

PMID- 28503464
TI  - Maximal Inspiratory Pressure and Maximal Expiratory Pressure in Healthy Korean
      Children.
AB  - OBJECTIVE: To evaluate respiratory muscle strength in healthy Korean children in
      order to establish the criteria for normal reference values for future
      applications. In contrast with the other parameters for testing pulmonary
      function, normal values for respiratory muscle strength in healthy Korean
      children have not been assessed to date. METHODS: We conducted a complete survey
      of 263 students at Sinmyung Elementary School in Yangsan, Gyeongsangnam-do, and
      measured their height and body weight, performed pulmonary function tests, and
      evaluated maximal inspiratory pressure (MIP) and maximal expiratory pressure
      (MEP) as measures of respiratory muscle strength. We excluded the subjects with
      respiratory or cardiovascular diseases that could affect the results. The
      subjects were children aged 8-12 years, and they consisted of 124 boys and 139
      girls. RESULTS: The MIP and MEP values (mean+/-standard deviation) for the entire
      subject group were 48.46+/-18.1 cmH2O and 47.95+/-16 cmH2O, respectively. Boys
      showed higher mean values for MIP and MEP in every age group. Korean children
      showed lower mean values for MIP and MEP compared to those in previous studies
      conducted in other countries (Brazil and USA). CONCLUSION: Our results showed
      that boys generally have greater respiratory muscle strength than girls. We found
      a significant difference between the results of our study and those of previous
      studies from other countries. We speculate that this may be attributed to
      differences in ethnicity, nutrition, or daily activities.

PMID- 28503465
TI  - Correlation of Serum Creatine Kinase Level With Pulmonary Function in Duchenne
      Muscular Dystrophy.
AB  - OBJECTIVE: To investigate the relationship between serum creatine kinase (CK)
      level and pulmonary function in Duchenne muscular dystrophy (DMD). METHODS: A
      total of 202 patients with DMD admitted to the Department of Rehabilitation
      Medicine, Gangnam Severance Hospital were enrolled from January 1, 1999 to March
      31, 2015. Seventeen patients were excluded. Data collected from the 185 patients
      included age, height, weight, body mass index, pulmonary function tests including
      forced vital capacity (FVC), peak cough flow, maximal expiratory pressure (MEP),
      and maximal inspiratory pressure (MIP), and laboratory measurements (serum level
      of CK, CK-MB, troponin-T, and B-type natriuretic peptide). FVC, MEP, and MIP were
      expressed as percentages of predicted normal values. RESULTS: Serum CK activities
      were elevated above normal levels, even in the oldest DMD group. Serum CK level
      was strongly correlated with pulmonary functions of sitting FVC (p<0.001), supine
      FVC (p<0.001), MIP (p=0.004), and MEP (p<0.001). CONCLUSION: Serum CK level is a
      reliable screening test even in patients with advanced DMD, and is a strong
      predictor of pulmonary functions.

PMID- 28503466
TI  - Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous
      Xanthomatosis: A Case Report.
AB  - Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that
      involves multiple organs, including the peripheral nervous system. The present
      study is the first to report the ultrasonographic findings of peripheral nerves
      in a patient with cerebrotendinous xanthomatosis. The patient presented with
      bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic
      examination revealed hypoechoic, swollen peripheral nerves with enlarged
      bilateral Achilles tendons. Since the ultrasonographic findings revealed
      peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was
      established after laboratory and genetic studies along with clinical findings.

PMID- 28503468
TI  - Extravasation of the Contrast Material During Voiding Cystourethrography in a
      Chronic Spinal Cord Injury Patient: A Case Report.
AB  - Neurogenic bladder is common in most spinal cord injury patients. Voiding
      cystourethrography (VCUG) is recommended in these patients to detect urinary
      tract complications. However, rare but serious complications may occur during
      VCUG, although VCUG is generally safe. There are several case reports of bladder
      rupture occurring in pediatric patients. Here, we report the first case of
      iatrogenic bladder rupture in an adult spinal cord injury patient in Korea.
      Particularly, extravasation of contrast without manual instillation has hardly
      ever been reported. To the best of our knowledge, this is the first reported case
      of bladder rupture without manual instillation during VCUG. We report a case of a
      59-year-old female with paraplegia due to tuberculous spondylitis who underwent
      VCUG as a part of routine evaluation of neurogenic bladder. Extravasation of the
      contrast media during VCUG developed as a complication and the patient recovered
      spontaneously without any intervention. Therefore, VCUG should be performed
      properly in chronic spinal cord injury patients.

PMID- 28503467
TI  - Medial Lemniscus Tract Lesion After High Voltage Electrical Injury: A Case
      Report.
AB  - We present the case of a 33-year-old man who experienced a 10,000-V electrical
      shock when working with electrical wiring. He suffered third-degree burns on his
      scalp at the right occiput (entry wound) and on his left arm (exit would), and a
      second-degree burn on his left foot (exit wound). He presented with severe
      spasticity of both lower extremities, motor weakness with a Medical Research
      Council grade of 3, and sensory impairments below thoracic level 11 that included
      an inability to sense light touch and defects in proprioception. Initial magnetic
      resonance imaging (MRI) scans of his spine and brain showed no definite
      abnormalities. However, tractography obtained by diffusion tensor imaging of the
      brain showed absence of the right medial lemniscus tract. A cervical MRI scan 1
      month later showed spinal cord swelling from cervical 1-5 levels, and signal
      changes in the lateral and posterior white matter in the axial view. After 6
      months of rehabilitation, he recovered almost normal degree of motor function in
      his lower extremities and disappearance of spasticity. However, since the sensory
      impairments persisted, especially defects in proprioception, he was unable to
      walk independently.

PMID- 28503469
TI  - Motor Neuron Disease Presenting With Acute Respiratory Failure: A Case Study.
AB  - Motor neuron diseases (MNDs) refer to a heterogeneous group of progressive
      neurologic disorders caused by degeneration of motor neurons. The diseases affect
      either the upper motor neurons, lower motor neurons, or both, and are
      characterized by weakness, atrophy, fasciculation, spasticity, and respiratory
      failure. We report a case of a 61-year-old male patient with no past history of
      cardiovascular or pulmonary disease, who presented with only dyspnea, and no
      indication of any other symptom such as muscle weakness, atrophy, or bulbar
      dysfunction. Neuromuscular conduction study, including a study of the phrenic
      nerve, confirmed the diagnosis of MND. The patient greatly improved giving
      respiratory assistance at night, using a noninvasive ventilator. This case
      indicates that MNDs should be considered as differential diagnoses for patients
      showing acute respiratory failure of unknown causes. This report will aid in the
      prompt diagnosis and treatment of MNDs.

PMID- 28503470
TI  - Falsely Elevated Postvoid Residual Urine Volume in Uterine Myoma.
AB  - Precise measurement of postvoid residual (PVR) urine volume is a key factor in
      assessing patients with voiding dysfunction, including those with lower urinary
      tract problems. The safe and noninvasive ultrasound bladder scan is the preferred
      mode to measure PVR volume. However, this procedure has a false-positive rate up
      to 9%, in the presence of ovarian cysts, renal cysts, ascites, or uterine myoma
      with cystic degeneration. Until now, cystic lesions are known to cause false
      positivity in ultrasound bladder scanner. However, we encountered falsely
      elevated PVR in two cases of non-cystic uterine myomas. We present these cases
      with detailed radiologic images and volume measurement data.

PMID- 28503471
TI  - Correction: Effectiveness of Lower Energy Density Extracorporeal Shock Wave
      Therapy in the Early Stage of Avascular Necrosis of the Femoral Head.
AB  - [This corrects the article on p. 871 in vol. 40, PMID: 27847717.].

PMID- 28503472
TI  - Recognition and management of palatogingival groove for tooth survival: a
      literature review.
AB  - Palatogingival groove (PGG) is an anomaly in the maxillary anterior teeth, often
      accompanied by the area of bony destruction adjacent to the teeth with no carious
      or traumatic history. The hidden trap in the tooth can harbor plaque and
      bacteria, resulting in periodontal destruction with or without pulpal pathologic
      change. Related diseases can involve periodontal destruction, combined endodontic
      periodontal lesions, or separate endodontic and periodontal lesions. Disease
      severity and prognosis related to PGG depend on several factors, including
      location, range, depth, and type of the groove. Several materials have been used
      and recommended for cases of extensive periodontal destruction from PGG to remove
      and block the inflammatory source and recover the health of surrounding
      periodontal tissues. Even in cases of severe periodontal destruction, several
      studies have reported favorable treatment outcomes with proper management. With
      new options in diagnosis and treatment, clinicians need a detailed understanding
      of the characteristics, treatment, and prognosis of PGG to successfully manage
      the condition.

PMID- 28503473
TI  - Analysis of the shelf life of chitosan stored in different types of packaging,
      using colorimetry and dentin microhardness.
AB  - OBJECTIVES: Chitosan has been widely investigated and used. However, the
      literature does not refer to the shelf life of this solution. This study
      evaluated, through the colorimetric titration technique and an analysis of dentin
      micro-hardness, the shelf life of 0.2% chitosan solution. MATERIALS AND METHODS:
      Thirty human canines were sectioned, and specimens were obtained from the second
      and third slices, from cemento-enamel junction to the apex. A 0.2% chitosan
      solution was prepared and distributed in 3 identical glass bottles (v1, v2, and
      v3) and 3 plastic bottles (p1, p2, and p3). At 0, 7, 15, 30, 45, 60, 90, 120,
      150, and 180 days, the specimens were immersed in each solution for 5 minutes (n
      = 3 each). The chelating effect of the solution was assessed by micro-hardness
      and colorimetric analysis of the dentin specimens. 17% EDTA and distilled water
      were used as controls. Data were analyzed statistically by two-way and Tukey
      Kramer multiple comparison (alpha = 0.05). RESULTS: There was no statistically
      significant difference among the solutions with respect to the study time (p =
      0.113) and micro-hardness/time interaction (p = 0.329). Chitosan solutions and
      EDTA reduced the micro-hardness in a similar manner and differed significantly
      from the control group (p < 0.001). Chitosan solutions chelated calcium ions
      throughout the entire experiment. CONCLUSIONS: Regardless of the storage form,
      chitosan demonstrates a chelating property for a minimum period of 6 months.

PMID- 28503474
TI  - Bonding of the silane containing multi-mode universal adhesive for lithium
      disilicate ceramics.
AB  - OBJECTIVES: This study evaluated the influence of a multi-mode universal adhesive
      (MUA) containing silane (Single Bond Universal, 3M EPSE) on the bonding of resin
      cement to lithium disilicate. MATERIALS AND METHODS: Thirty IPS e.max CAD
      specimens (Ivoclar Vivadent) were fabricated. The surfaces were treated as
      follows: Group A, adhesive that did not contain silane (ANS, Porcelain Bonding
      Resin, Bisco); Group B, silane (S) and ANS; Group C, hydrofluoric acid (HF), S,
      and ANS; Group D, MUA; Group E, HF and MUA. Dual-cure resin cement (NX3, Kerr)
      was applied and composite resin cylinders of 0.8 mm in diameter were placed on it
      before light polymerization. Bonded specimens were stored in water for 24 hours
      or underwent a 10,000 thermocycling process prior to microshear bond strength
      testing. The data were analyzed using multivariate analysis of variance (p <
      0.05). RESULTS: Bond strength varied significantly among the groups (p < 0.05),
      except for Groups A and D. Group C showed the highest initial bond strength (27.1
      +/- 6.9 MPa), followed by Group E, Group B, Group D, and Group A. Thermocycling
      significantly reduced bond strength in Groups B, C, and E (p < 0.05). Bond
      strength in Group C was the highest regardless of the storage conditions (p <
      0.05). CONCLUSIONS: Surface treatment of lithium disilicate using HF and silane
      increased the bond strength of resin cement. However, after thermocycling, the
      silane in MUA did not help achieve durable bond strength between lithium
      disilicate and resin cement, even when HF was applied.

PMID- 28503475
TI  - The use of auxiliary devices during irrigation to increase the cleaning ability
      of a chelating agent.
AB  - OBJECTIVES: This study investigated the cleaning ability of ultrasonically
      activated irrigation (UAI) and a novel activation system with reciprocating
      motion (EC, EasyClean, Easy Equipamentos Odontologicos) when used with a
      relatively new chelating agent (QMix, Dentsply). In addition, the effect of QMix
      solution when used for a shorter (1 minute) and a longer application time (3
      minutes) was investigated. MATERIALS AND METHODS: Fifty permanent human teeth
      were prepared with K3 rotary system and 6% sodium hypochlorite. Samples were
      randomly assigned to five groups (n = 10) according to the final irrigation
      protocol: G1, negative control (distilled water); G2, positive control (QMix 1
      minute); G3, QMix 1 minute/UAI; G4, QMix 1 minute/EC; G5, QMix 3 minutes.
      Subsequently the teeth were prepared and three photomicrographs were obtained in
      each root third of root walls, by scanning electron microscopy. Two blinded and
      pre-calibrated examiners evaluated the images using a four-category scoring
      system. Data were statistically analyzed using Kruskal-Wallis and Dunn tests (p <
      0.05). RESULTS: There were differences among groups (p < 0.05). UAI showed better
      cleaning ability than EC (p < 0.05). There were improvements when QMix was used
      with auxiliary devices in comparison with conventional irrigation (p < 0.05).
      Conventional irrigation for 3 minutes presented significantly better results than
      its use for 1 minute (p < 0.05). CONCLUSIONS: QMix should be used for 1 minute
      when it is used with UAI, since this final irrigation protocol showed the best
      performance and also allowed clinical optimization of this procedure.

PMID- 28503476
TI  - Differential diagnosis of periapical cyst using collagen birefringence pattern of
      the cyst wall.
AB  - OBJECTIVES: Periapical lesions, including periapical cyst (PC), periapical
      granuloma (PG), and periapical abscess (PA), are frequently affected by
      chemical/physical damage during root canal treatment or severe bacterial
      infection, and thus, the differential diagnosis of periapical lesions may be
      difficult due to the presence of severe inflammatory reaction. The aim of this
      study was to make differential diagnosis among PC, PG, and PA under polarizing
      microscope. MATERIALS AND METHODS: The collagen birefringence patterns of 319
      cases of PC (n = 122), PG (n = 158), and PA (n = 39) obtained using a polarizing
      microscope were compared. In addition, 6 cases of periodontal fibroma (PF) were
      used as positive controls. RESULTS: Collagen birefringence was condensed with a
      thick, linear band-like pattern in PC, but was short and irregularly scattered in
      PG, and scarce or absent in PA. PF showed intense collagen birefringence with a
      short, palisading pattern but no continuous band-like pattern. The linear band
      like birefringence in PC was ascribed to pre-existing expansile tensile stress of
      the cyst wall. CONCLUSIONS: In this study all PCs (n = 122) were distinguishable
      from PGs and PAs by their characteristic birefringence, despite the absence of
      lining epithelium (n = 20). Therefore, the authors suggest that the presence of
      linear band-like collagen birefringence of the cyst wall aids the diagnostic
      differentiation of PC from PG and PA.

PMID- 28503478
TI  - The effects of non-thermal plasma and conventional treatments on the bond
      strength of fiber posts to resin cement.
AB  - OBJECTIVES: This study compared the effect of hexamethyldisiloxane (HMDSO) and
      ammonia (NH3) plasmas on the bond strength of resin cement to fiber posts with
      conventional treatments. MATERIALS AND METHODS: Sixty-five fiber posts were
      divided into 5 groups: Control (no surface treatment); H2O2 (24% hydrogen
      peroxide for 1 min); Blasting (blasting with aluminum oxide for 30 sec); NH3 (NH3
      plasma treatment for 3 min); HMDSO (HMDSO plasma treatment for 15 min). After the
      treatments, the Ambar adhesive (FGM Dental Products) was applied to the post
      surface (n = 10). The fiber post was inserted into a silicon matrix that was
      filled with the conventional resin cement Allcem Core (FGM). Afterwards, the
      post/cement specimens were cut into discs and subjected to a push-out bond
      strength (POBS) test. Additionally, 3 posts in each group were evaluated using
      scanning electron microscopy. The POBS data were analyzed by one-way analysis of
      variance and the Tukey's honest significant difference post hoc test (alpha =
      0.05). RESULTS: The Blasting and NH3 groups showed the highest POBS values. The
      HMDSO group showed intermediate POBS values, whereas the Control and H2O2 groups
      showed the lowest POBS values. CONCLUSION: Blasting and NH3 plasma treatments
      were associated with stronger bonding of the conventional resin cement Allcem to
      fiber posts, in a procedure in which the Ambar adhesive was used.

PMID- 28503477
TI  - Color stability of bulk-fill and incremental-fill resin-based composites polished
      with aluminum-oxide impregnated disks.
AB  - OBJECTIVES: This study aimed to evaluate the color stability of bulk-fill and
      nanohybrid resin-based composites polished with 3 different, multistep, aluminum
      oxide impregnated finishing and polishing disks. MATERIALS AND METHODS: Disk
      shaped specimens (8 mm in diameter and 4 mm in thickness) were light-cured
      between two glass slabs using one nanohybid bulk-fill (Tetric EvoCeram, Ivoclar
      Vivadent), one micro-hybrid bulk-fill (Quixfil, Dentsply), and two nanohybrid
      incremental-fill (Filtek Ultimate, 3M ESPE; Herculite XRV Ultra, Kerr) resin
      based composites, and aged by thermocycling (between 5 - 55C, 3,000 cycles).
      Then, they were divided into subgroups according to the polishing procedure as
      SwissFlex (Coltene/Whaledent), Optidisc (Kerr), and Praxis TDV (TDV Dental) (n =
      12 per subgroup). One surface of each specimen was left unpolished. All specimens
      were immersed in coffee solution at 37C. The color differences (DeltaE) were
      measured after 1 and 7 days of storage using a colorimeter based on CIE Lab
      system. The data were analyzed by univariate ANOVA, Mann-Whitney U test, and
      Friedmann tests (alpha = 0.05). RESULTS: Univariate ANOVA detected significant
      interactions between polishing procedure and composite resin and polishing
      procedure and storage time (p < 0.05). Significant color changes were detected
      after 1 day storage in coffee solution (p < 0.05), except Quixfil/Optidisc which
      was color-stable after 7 days (p > 0.05). Polishing reduced the discoloration
      resistance of Tetric EvoCeram/SwissFlex, Tetric EvoCeram/Praxis TDV, Quixfil
      SwissFlex, and all Herculite XRV Ultra groups after 7 days storage (p < 0.05).
      CONCLUSIONS: Discoloration resistance of bulk-fill resin-based composites can be
      significantly affected by the polishing procedures.

PMID- 28503479
TI  - Cyclic fatigue life of Tango-Endo, WaveOne GOLD, and Reciproc NiTi instruments.
AB  - OBJECTIVES: To compare the fatigue life of Tango-Endo, WaveOne GOLD, and Reciproc
      NiTi instruments under static model via artificial canals with different angles
      of curvature. MATERIALS AND METHODS: Reciproc R25, WaveOne GOLD Primary, and
      Tango-Endo instruments were included in this study (n = 20). All the instruments
      were rotated in artificial canals which were made of stainless steel with an
      inner diameter of 1.5 mm, 45 degrees , 60 degrees , and 90 degrees  angles of
      curvatures and a radius of curvature of 5 mm until fracture occurred, and the
      time to fracture was recorded in seconds using a digital chronometer. The data
      were analyzed using Kruskal-Wallis and post-hoc Dunn tests were used for the
      statistical analysis of data in SPSS 21.0 software. RESULTS: Tango-Endo files
      were found to have significantly higher values than WaveOne GOLD and Reciproc
      files in terms of fatigue life (p < 0.05). However, there was no statistically
      significant difference between fatigue life of Reciproc and WaveOne GOLD files (p
      > 0.05). It was determined that increasing the angle of curvature of the
      stainless canals caused significant decreases in fatigue life of all of three
      files (p < 0.05). CONCLUSIONS: Within the limitations of the present study, the
      cyclic fatigue life of Tango-Endo in canals having different angles of curvature
      was statistically higher than Reciproc and WaveOne GOLD.

PMID- 28503480
TI  - Intraoperative discomfort associated with the use of a rotary or reciprocating
      system: a prospective randomized clinical trial.
AB  - OBJECTIVES: The aim of this randomized, controlled, prospective clinical study
      was to evaluate patients' intraoperative discomfort during root canal
      preparations in which either multi-file rotary (Mtwo) or single-file
      reciprocating (Reciproc) systems were used. MATERIALS AND METHODS: Fifty-five
      adult patients, aged between 25 and 69 years old, with irreversible pulpitis or
      pulp necrosis participated in this study. Either the mesiobuccal or the
      distobuccal canals for maxillary molars and either the mesiobuccal or the
      mesiolingual canals for mandibular molars were randomly chosen to be instrumented
      with Mtwo multi-file rotary or Reciproc single-file reciprocating systems.
      Immediately after each canal instrumentation under anesthesia, patient discomfort
      was assessed using a 1 - 10 visual analog scale (VAS), ranging from 'least
      possible discomfort' (1) to 'greatest possible discomfort' (10). The Wilcoxon
      signed-rank test was used to determine significant differences at p< 0.05.
      RESULTS: Little intraoperative discomfort was found in all cases. No
      statistically significant differences in intraoperative discomfort between the 2
      systems were found (p = 0.660). CONCLUSIONS: Root canal preparation with multi
      file rotary or single-file reciprocating systems had similar and minimal effects
      on patients' intraoperative discomfort.

PMID- 28503482
TI  - Statistical notes for clinical researchers: Chi-squared test and Fisher's exact
      test.

PMID- 28503481
TI  - Dental management of patients with X-linked hypophosphatemia.
AB  - X-linked hypophosphatemia (XLH) is a hereditary metabolic disease caused by the
      loss of phosphate through the renal tubules into the urine, and an associated
      decrease in serum calcium and potassium phosphate. Its dental features include
      spontaneous dental abscesses that occur in the absence of trauma or dental
      caries. The aim of this case report was to describe the dental problems of XLH
      patients and to evaluate limitations in their treatment. A 14 year old male and a
      38 year old female with XLH were referred to the Department of Conservative
      Dentistry for endodontic treatment. The dental findings were periapical abscesses
      without obvious trauma or caries. Conservative endodontic treatment was performed
      in teeth with pulp necrosis and abscess. In case 1, the treated teeth showed
      improvements in bone healing, without clinical symptoms. However, in case 2, the
      implants and the treated tooth showed hypermobility, and the final restoration
      was therefore postponed. Early diagnosis, periodic examinations, and
      communication with the patient's pediatrician are important in the dental
      management of patients with XLH.

PMID- 28503483
TI  - Importance of Hematoma Removal Ratio in Ruptured Middle Cerebral Artery Aneurysm
      Surgery with Intrasylvian Hematoma.
AB  - OBJECTIVE: Ruptured middle cerebral artery (MCA) aneurysm with intrasylvian
      hematoma usually accompanied by progressive cerebral swelling with poorer
      outcomes. The authors present characteristics and importance of intrasylvian
      hematoma removal in the aneurysm surgery. MATERIALS AND METHODS: From 2012
      February to 2014 March, 24 aneurysm surgeries for ruptured MCA aneurysms with
      intrasylvian hematoma were performed in the authors' clinic. The patients were
      classified according to three groups. Group A included patients who underwent
      decompressive craniectomy within a few days after aneurysm surgery due to
      progressive cerebral swelling, group B included patients for whom decompression
      was not necessary, and group C included patients who showed severe cerebral
      swelling on admission and decompressive craniectomy and aneurysm surgery in one
      stage. RESULTS: The mean hematoma volume on admission was 28.56 mL, 24.96 mL, and
      66.78 mL for groups A, B and C, respectively. Removal of a larger amount of
      hematoma was observed on postoperative computerized tomography scan in groups B
      and C (63.2% and 59.0%) compared with group A (33.4%). Although no statistical
      difference was found between group A and group B (p = 0.115), it tends to show
      the lesser amount of hematoma removed, the more likely cerebral swelling will
      progress. CONCLUSION: The lesser amount of hematoma in ruptured MCA aneurysm with
      intrasylvian hematoma tends to show benign clinical course than larger amounts.
      But, even if the hematoma is not easily removed in the operation, we suggest the
      other procedures such as continuous external catheter drainage of hematoma to
      avoid unnecessary coagulation or brain retraction.

PMID- 28503484
TI  - Prophylactic Dual Catheter Technique to Prevent Side Branch Snowplowing
      Complications during Angioplasty and Stenting.
AB  - OBJECTIVE: Angioplasty and Stenting of intracranial atherosclerotic lesions have
      a higher complication rate and a large proportion of this is attributable to side
      branch arterial occlusion from forceful displacement of the atheroma into the
      ostia or snowplowing effect. This can result in severe disabilities when it
      result in small infarcts involving eloquent areas in the posterior circulation or
      the motor tracts. MATERIALS AND METHODS: We present a series of 6 cases utilizing
      a new dual catheter technique for maintaining the patency of at-risk vessels
      during angioplasty and stenting. There are several methods previously described
      to help reduce the incidence of stroke but because they do not have a physical
      presence in the ostia to protect it, they are unable to guarantee the patency of
      the vessel. RESULTS: All 6 patients underwent angioplasty and stenting with the
      technique. The patients were assessed for complications with post-procedure
      magnetic resonance imaging and no complications were found. CONCLUSION: In this
      preliminary series, the dual catheter technique appears to safe and effective in
      preventing occlusion of the adjacent branch arteries. This technique may
      facilitate the use of the Wingspan stent in the treatment of intracranial
      atherosclerotic stenotic segments by reducing the risk of peri-procedural stroke.

PMID- 28503487
TI  - Discrepancy between Angiography and Operative Findings of Small Side Wall
      Aneurysms in Atherosclerotic Parent Arteries.
AB  - Preoperative evaluation of precise aneurysmal geometry is important for the
      treatment of intracranial aneurysms. We present two cases of unclippable side
      wall aneurysms due to their extremely low dome height, which appeared as saccular
      in the preoperative image because of a comparatively narrow atherosclerotic
      parent arterial lumen. In both cases, a calcified vessel wall was noted
      preoperatively. Lack of a definitive neck and abrupt discrepancy between the
      fragile aneurysmal wall and the atherosclerotic parent arterial wall was
      confirmed intraoperatively in both cases. This study describes an illustrative
      mechanism for the finding with emphasis on the importance of its preoperative
      diagnosis. Intracranial atherosclerosis associated with small side walled
      aneurysms may lead to overestimation of aneurysm height on preoperative imaging
      of the intravascular compartment.

PMID- 28503485
TI  - Surgical Approaches for Symptomatic Cerebral Cavernous Malformations of the
      Thalamus and Brainstem.
AB  - OBJECTIVE: Surgical resection of thalamic and brainstem cerebral cavernous
      malformations (CCMs) is associated with significant operative morbidity, but it
      may be outweighed, in some cases, by the neurological damage from recurrent
      hemorrhage in these eloquent areas. The goals of this retrospective cohort study
      are to describe the technical nuances of surgical approaches and determine the
      postoperative outcomes for CCMs of the thalamus and brainstem. MATERIALS AND
      METHODS: We reviewed an institutional database of patients harboring thalamic or
      brainstem CCMs, who underwent surgical resection from 2010 to 2014. The baseline
      and follow-up neuroimaging and clinical findings of each patient and the
      operative details of each case were evaluated. RESULTS: A total of eight
      patients, including two with thalamic and six with brainstem CCMs, were included
      in the study cohort. All patients had progressive neurological deterioration from
      recurrent CCM hemorrhage, and the median modified Rankin Scale (mRS) at
      presentation was 3. The median CCM maximum diameter and volume were 1.7 cm and
      1.8 cm3, respectively. The thalamic CCMs were resected using the anterior
      transcallosal transchoroidal and supracerebellar infratentorial approaches each
      in one case (13%). The brainstem CCMs were resected using the retrosigmoid and
      suboccipital trans-cerebellomedullary fissure approaches each in three cases
      (38%). After a median follow-up of 11.5 months, all patients were neurologically
      stable or improved, with a median mRS of 2. The rate of functional independence
      (mRS 0-2) was 63%. CONCLUSION: Microneurosurgical techniques and approaches can
      be safely and effectively employed for the management of thalamic and brainstem
      CCMs in appropriately selected patients.

PMID- 28503486
TI  - The Rupture Risk of Aneurysm in the Anterior Communicating Artery: A Single
      Center Study.
AB  - OBJECTIVE: The aim of this study was to evaluate the characteristics of ruptured
      aneurysms at anterior communicating artery (A com) with an analysis of clinical
      and morphological data, which could further our understanding of the risks of
      ruptured A com aneurysms. MATERIALS AND METHODS: An analysis of data with 86
      ruptured and 44 unruptured A com aneurysms were analyzed using a digital
      subtraction angiography or 3-dimensional computed tomography angiography between
      January 2010 and December 2015 in a single center. RESULTS: Fifty-five percent of
      ruptured A com aneurysms were smaller than 4 mm in size. They had a smooth wall
      (44%), with a mean size ratio of 4.22 (range: 0.7-14.3) and mean height/width
      ratio of 1.48 (range: 0.5-2.9); 23 patients of A1 positive difference. Unruptured
      aneurysms were mostly 2-10 mm in size (94%) and had an irregular wall (43%), with
      a mean size ratio of 4.1 (range: 0.8-9.1) and mean height/width ratio of 1.2
      (range: 0.1-2.6); 6 patients of A1 positive difference. In terms of the
      morphology of aneurysms, size of A com, maximum aneurysm size, neck width,
      aneurysm wall morphology, and size ratio were not different with statistical
      significance. However, dominance of A1 (p = 0.01) and height/width ratio (p =
      0.03) were found to be a significant predictive factor for rupture of A com
      aneurysms. CONCLUSION: To better understand the rupture risk of A com aneurysms,
      a large, multicenter, collaborative, and prospective study should be performed in
      the future.

PMID- 28503488
TI  - Treatment of Cerebral Vasospasm in an Infant Using a Modified Dotter Technique.
AB  - An 8-month old female presented with spontaneous subarachnoid hemorrhage and was
      treated successfully with endovascular coil embolization of the ruptured
      aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated
      middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and
      greater than 200 cm/sec on the left, despite medical management. The patient
      demonstrated no focal neurological deficits, though examination was limited by
      our patient's sedation and intubation. Angiography revealed severe vasospasm of
      the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm
      was refractory to the administration of intra-arterial verapamil. Balloon
      angioplasty was attempted, but the device could not be advanced safely due to the
      small size of the patient's vessels and the stiffness of the device. A
      microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire
      (0.014" diameter) to perform mechanical angioplasty in the internal carotid
      artery and MCA vessels bilaterally. Dramatic improvement was seen
      angiographically and on transcranial Doppler, and no complications were seen.

PMID- 28503489
TI  - Spontaneous Absorption of Cerebral Air Emboli.

PMID- 28503491
TI  - Variation in the Distribution of Putative Virulence and Colonization Factors in
      Shiga Toxin-Producing Escherichia coli Isolated from Different Categories of
      Cattle.
AB  - Shiga toxin-producing Escherichia coli (STEC) are pathogens of significant public
      health concern. Several studies have confirmed that cattle are the main reservoir
      of STEC in Argentina and other countries. Although Shiga toxins represent the
      primary virulence factors of STEC, the adherence and colonization of the gut are
      also important in the pathogenesis of the bacteria. The aim of this study was to
      analyze and to compare the presence of putative virulence factors codified in
      plasmid -katP, espP, subA, stcE- and adhesins involved in colonization of cattle 
      efa1, iha- in 255 native STEC strains isolated from different categories of
      cattle from different production systems. The most prevalent gene in all strains
      was espP, and the less prevalent was stcE. katP was highly detected in strains
      isolated from young and rearing calves (33.3%), while subA was predominant in
      those isolated from adults (71.21%). Strains from young calves showed the highest
      percentage of efa1 (72.46%), while iha showed a high distribution in strains from
      rearing calves and adults (87.04 and 98.48% respectively). It was observed that
      espP and iha were widely distributed throughout all strains, whereas katP, stcE,
      and efa1 were more associated with the presence of eae and subA with the eae
      negative strains. A great proportion of eae-negative strains were isolated from
      adults -dairy and grazing farms- and from rearing calves -dairy and feedlot-,
      while mostly of the eae-positive strains were isolated from dairy young calves.
      Data exposed indicate a correlation between the category of the animal and the
      production systems with the presence or absence of several genes implicated in
      adherence and virulence of STEC.

PMID- 28503492
TI  - Positive Effect of Probiotics on Constipation in Children: A Systematic Review
      and Meta-Analysis of Six Randomized Controlled Trials.
AB  - Context: Constipation in children is a prevalent, burdensome, and psychologically
      important pediatric issue, the treatment of which remains a global challenge. The
      use of probiotics has been reported for management of the gastrointestinal
      microbiota. Objective: This study reviewed the existing literatures of 6
      Randomized Control Trials (RCTs) to ascertain some baseline understanding and
      available information for the effects of probiotics on stool frequency and
      consistency in children with constipation. Data Sources: PubMed, Springer,
      Elsevier Science, Cochrane Library, Scopus, Ovid (Medline, EMBASE, PsycINFO),
      Orbis, and Web of Science from the earliest record in each database to 15
      September, 2016. Study selection: Eligible studies were randomized controlled
      trials that compared the effect of probiotics interventions to any control
      intervention on stool frequency and consistency. Data Extraction: Studies were
      identified by searching electronic databases. The meta-analysis was performed by
      Review Manager 5.3 software using a randomized model. Results: Six studies were
      identified. The use of probiotics significantly increased the stool frequency
      [mean difference (MD), 0.73; 95% confidence interval (CI), 0.14-1.31; P = 0.02].
      Subgroup assessment showed a significantly increased stool frequency in Asian
      patients (MD, 1.18; 95% CI, 0.33-2.02; P = 0.006), but no significant difference
      in stool consistency (MD, -0.07; 95% CI, -0.21-0.06; P = 0.27). Limitations: Only
      six RCTs met the criteria and were included. Each RCT in this study was performed
      in a different country, and some of the included studies had a small sample size,
      which might have influenced the reliability and validity of the conclusions.
      Conclusion: The present study shows that probiotics increase stool frequency and
      have beneficial effects in Asian children. However, caution is needed when
      interpreting these outcomes because of the existence of heterogeneity. Evidence
      from larger samples and more adequately powered RCTs with results obtained by
      standardized measurements are necessary to determine which species and dosage of
      probiotics and what length of treatment are most efficacious for constipation in
      children.

PMID- 28503493
TI  - The Effect of Active Treatment and Visit Compared to Conventional Treatment, on
      Preventing Recurrent Suicidal Attempts: A Randomized Controlled Clinical Trial.
AB  - BACKGROUND: Suicide is a major problem, and its prevention is a global priority.
      In many cases, suicide attempter attempts to do it again after the rescue. In
      current study we aimed to compare active visit and treatment of patients in a
      periodic manner with treatment as usual, in the prevention of recurrent suicidal
      attempts. MATERIALS AND METHODS: This study was a randomized controlled clinical
      trial which was conducted in Isfahan Noor Hospital's Emergency Center on 60
      patients in 2013-2014. The samples were selected using simple random sampling and
      they were assigned into two groups: The conventional treatment group (treatment
      as usual) (30 patients), and visit and active treatment (30 patients). In the
      intervention group, there were ten follow-ups by a face-to-face visit over 12
      months, and six follow-ups by phone call in control group. Through the completion
      of the initial and follow-up questionnaire evaluation was performed. The data
      were analyzed using Cochran test, and repeated measure (ANOVA). RESULTS: During
      the 12-month follow-up visit and active treatment, significant difference in
      reducing suicidal thoughts (P = 0.003) was observed and an increase in the life
      expectancy (P = 0.001), interest and motivation in life (P = 0.001) was found in
      the intervention group, and also nonsignificant reduction was found in the rate
      of suicidal attempts. CONCLUSION: Visit and active treatment is useful in suicide
      attempters and it can helps in preventing recurrent suicide attempt as a
      preventive program by increasing hope and reducing suicidal thoughts.

PMID- 28503490
TI  - The Distinct Transcriptional Response of the Midgut of Amblyomma sculptum and
      Amblyomma aureolatum Ticks to Rickettsia rickettsii Correlates to Their
      Differences in Susceptibility to Infection.
AB  - Rickettsia rickettsii is a tick-borne obligate intracellular bacterium that
      causes Rocky Mountain Spotted Fever (RMSF). In Brazil, two species of ticks in
      the genus Amblyomma, A. sculptum and A. aureolatum, are incriminated as vectors
      of this bacterium. Importantly, these two species present remarkable differences
      in susceptibility to R. rickettsii infection, where A. aureolatum is more
      susceptible than A. sculptum. In the current study, A. aureolatum and A. sculptum
      ticks were fed on suitable hosts previously inoculated with R. rickettsii,
      mimicking a natural infection. As control, ticks were fed on non-infected
      animals. Both midgut and salivary glands of all positively infected ticks were
      colonized by R. rickettsii. We did not observe ticks with infection restricted to
      midgut, suggesting that important factors for controlling rickettsial
      colonization were produced in this organ. In order to identify such factors, the
      total RNA extracted from the midgut (MG) was submitted to next generation RNA
      sequencing (RNA-seq). The majority of the coding sequences (CDSs) of A. sculptum
      differentially expressed by infection were upregulated, whereas most of modulated
      CDSs of A. aureolatum were downregulated. The functional categories that comprise
      upregulated CDSs of A. sculptum, for instance, metabolism, signal transduction,
      protein modification, extracellular matrix, and immunity also include CDSs of A.
      aureolatum that were downregulated by infection. This is the first study that
      reports the effects of an experimental infection with the highly virulent R.
      rickettsii on the gene expression of two natural tick vectors. The distinct
      transcriptional profiles of MG of A. sculptum and A. aureolatum upon infection
      stimulus strongly suggest that molecular factors in this organ are responsible
      for delineating the susceptibility to R. rickettsii. Functional studies to
      determine the role played by proteins encoded by differentially expressed CDSs in
      the acquisition of R. rickettsii are warranted and may be considered as targets
      for the development of strategies to control the tick-borne pathogens as well as
      to control the tick vectors.

PMID- 28503494
TI  - Intratumoral and Peritumoral Mast Cells in Malignant Melanoma: An
      Immunohistochemical Study.
AB  - BACKGROUND: The aim of the current study was to determine mast cell infiltration
      in malignant melanoma by immunohistochemistry method and its relationship with
      some of the cancer prognostic factors, including age, sex, and depth of the
      tumor. MATERIALS AND METHODS: In this retrospective analytic cross-sectional
      study, paraffin-embedded tissue blocks of patients with cutaneous malignant
      melanoma who had undergone excisional biopsy were studied. Mast cells count in
      studied cases in different stages of the tumor depth was evaluated by mast cell
      tryptase immunohistochemistry method. Mast cells infiltration was evaluated both
      inside the tumor and peritumoral area. Tumor infiltrating lymphocytes (TILs) was
      also determined. Distribution of intratumoral and peritumoral mast cells and TILs
      was compared in different stages tof tumor depth. RESULTS: In this study, 51
      cases with melanoma were studied. Mean +/- standard deviation (SD) of
      intratumoral mast cells in stages 1, 2, and 3 was 9.4 +/- 4.2, 10.8 +/- 5.1, and
      2.1 +/- 2.3, respectively (P = 0.000). Mean +/- SD of peritumoral mast cells in
      stages 1, 2 and 3 was 13.4 +/- 2.4, 16.6 +/- 2.4 and 8.2 +/- 4.6, respectively (P
      = 0.000). There was a significant direct relationship between depth of the tumor
      and TIL (P = 0.000) and distribution of intratumoral (P = 0.000) and peritumoral
      mast cells (P = 0.000). CONCLUSION: Lower distribution of intratumoral and
      peritumoral mast cells and TILs in higher stages of tumor depth in malignant
      melanoma suggests a possible inhibitory effect of infiltrating mast cells and
      lymphocytes on the progression of this tumor.

PMID- 28503495
TI  - The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A
      Randomized Controlled Trial.
AB  - BACKGROUND: This study was designed to evaluate the effect of melatonin on
      nonalcoholic fatty liver disease (NAFLD) in compared to placebo. MATERIALS AND
      METHODS: A total of 100 patients with histopathological diagnosis NAFLD in two
      groups of case and control received oral melatonin or placebo thrice daily for 3
      months. Collected data were weight, waist, systolic blood pressure (SBP),
      diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), high sensitive C-reactive protein (hsCRP), fatty liver
      grade, and side effects which were measured at baseline and after treatment
      period using standard clinical chemistry techniques. RESULTS: Before treatment
      the mean of weight, waist, SBP, DBP, ALT, AST, and hsCRP between cases and
      controls were similar (P > 0.5). After treatment, only the differences in the
      mean of hsCRP in cases was significantly lower than controls (P = 0.003). In case
      group, all variables after treatment were significantly decreased compare to
      baseline (P > 0.5) and only AST after treatment was similar to before treatment
      (P > 0.5). The mean of a decrease in the level of weight, waist, SBP, and ALT
      were not statistically significant between groups (P > 0.5). In the case group in
      compare to control group the level of DBP, AST, and hsCRP significantly more
      decreased. After treatment fatty, liver grade was statistically improved in more
      cases than controls (P = 0.001). Side effects were similar between the two
      groups. CONCLUSION: Melatonin significantly decreases liver enzymes, so the use
      of melatonin in patients with NAFLD can be effective.

PMID- 28503496
TI  - Prevalence of Acquired Carbapenemase Genes in Klebsiella Pneumoniae by Multiplex
      PCR in Isfahan.
AB  - BACKGROUND: Multi-drug resistant Klebsiella pneumoniae has been considered as a
      serious global threat. This study was done to investigate carbapenemase producing
      genomes among K. pneumoniae isolates in Isfahan, Central Iran. MATERIALS AND
      METHODS: In a cross-sectional study from 2011 to 2012, 29 carbapenem resistant
      (according to disc diffusion method) carbapenemase producing (according to
      modified Hodge test) K. pneumoniae strains were collected from Intensive Care
      Unit (ICUs) of Al-Zahra referral Hospital. In the strains with the lack of
      sensitivity to one or several carbapenems, beta-lactams, or beta-lactamases,
      there has been performed modified Hodge test to investigate carbapenmase and then
      only strains producing carbapenmases were selected for molecular methods.
      RESULTS: In this study, there have been 29 cases of K. pneumoniae isolated from
      hospitalized patients in the (ICU). Three cases (10.3%) contained blaVIM, 1 case
      (3.4%) contained blaIMP, and 1 case (3.4%) contained blaOXA. The genes blaNDM and
      blaKPC were not detected. Then, 16 cases (55.2%) from positive cases of K.
      pneumoniae were related to the chip, 4 cases (13.8%) to catheter, 6 cases (20.7%)
      to urine, and 3 cases (10.3%) to wound. CONCLUSION: It is necessary to monitor
      the epidemiologic changes of these carbapenemase genes in K. pneumoniae in our
      Hospital. More attention should be paid to nosocomial infection control measures.
      Other carbapenemase producing genes should be investigated.

PMID- 28503497
TI  - Investigation of Prognostic Factors and Survival without Recurrence in Patients
      with Breast Cancer.
AB  - BACKGROUND: One of the major consequences of breast cancer is the recurrence of
      the disease. The objective of present study was to estimate the 7-year survival
      without recurrence as well as the effective prognostic factors in recurrence.
      MATERIALS AND METHODS: This historical cohort survival analysis was conducted on
      1329 patients diagnosed with breast cancer in Motahari Breast Clinic, Shiraz,
      Iran between 2004 and 2011. We estimated the rate of survival without recurrence
      through the Kaplan-Meier method and the difference between the survival curves
      was investigated using the log-rank test. Furthermore, Cox regression model was
      used to model the effective factors in local recurrence as well as metastasis.
      RESULTS: The mean age of the patients was 54.8 +/- 11.4 years. Estrogen receptor
      positive, progesterone receptor positive, and human epidermal growth factor
      receptor-2 positive were observed in 70.6%, 66.6%, and 34.4% of the cases,
      respectively. The mean of the follow-up period was 3.7 +/- 1.8 years in all
      patients. The results of the Kaplan-Meier method revealed 1-, 3-, 5-, and 7-year
      rate of survival without recurrence as 96.4%, 78.4%, 66.3%, and 54.8%,
      respectively. There was a significant relationship between survival without
      recurrence and histology grade (hazard ratio [HR] = 1.66, P = 0.009), neural
      invasion (HR = 1.74, P = 0.006), and progesterone receptors (HR = 0.69, P =
      0.031). CONCLUSION: In this study, the rate of survival without recurrence in
      breast cancer was 54.8%. Among factors, histology grade and neural involvement at
      the time of diagnosis increased the chance of recurrence and progesterone
      receptors caused a longer interval between diagnosis and recurrence.

PMID- 28503498
TI  - Evaluation of Energy Balance on Human Telomerase Reverse Transcriptase (hTERT)
      Alternative Splicing by Semi-quantitative RT-PCR in Human Umbilical Vein
      Endothelial Cells.
AB  - BACKGROUND: Decreased high-energy phosphate level is involved in endothelial cell
      injury and dysfunction. Reduced telomerase activity in endothelial cells in
      parallel with reduced energy levels might be due to altered direction of
      alternative splicing machine as a complication of depleted energy during the
      process of atherosclerosis. MATERIALS AND METHODS: Isolated human umbilical vein
      endothelial cells (HUVECs) were treated for 24 hours by oligomycine (OM) and 2
      deoxy glucose (2-DG). After 24 hours, the effect of energy depletion on
      telomerase splicing pattern was evaluated using RT-PCR. Indeed, in both treated
      and untargeted cells, nitric oxide (NO) and von Willebrand factor (vWF) were
      measured. RESULTS: ATP was depleted in treated cells by 43.9% compared with
      control group. We observed a slight decrease in NO levels (P = 0.09) and vWF (P =
      0.395) in the setting of 49.36% ATP depletion. In both groups, no telomerase gene
      expression was seen. Telomerase and housekeeping gene expression were found in
      positive control group (colon cancer tissue) and sample tissue. CONCLUSIONS: The
      absence of telomerase gene expression in HUVECs might be due to the mortality of
      these cells or the low level of telomerase gene expression in these cells under
      normal circumstances.

PMID- 28503499
TI  - The Prevalence of Osmophobia in Migranous and Episodic Tension Type Headaches.
AB  - BACKGROUND: Migraines are a neurological disease, of which the most common
      symptom is an intense and disabling episodic headache. Many persons experience
      sensory hyper excitability manifested by photophobia, phonophobia and osmophobia.
      This study was planned to investigate the prevalence of osmophobia in migranous
      and episodic tension type headache (ETTH). MATERIALS AND METHODS: A semi
      structured questionnaire was administered to all patients to evaluate the
      eventual presence of osmophobia during a headache attack and different
      characteristics of osmophobia were determined. RESULTS: Osmophobia reported in
      84% with migranous headache with aura, 74% of migranous patients without aura and
      in 43.3% of those with ETTH. In 50% of patients, osmophobia was present in all of
      their headache attacks, 11.7% had osmophobia in more than half of their attacks
      (from 10 attacks they reported osmophobia in 5-9 ones) and others had this sign
      in less than half of their attacks (from 10 attacks they reported osmophobia in
      less than 5 ones). Most frequently the offending odors were scents (88%), foods
      (54.2%) and cigarette smoke (62.5%). Osmophobia starts 30 min before the headache
      starts in 22.7% of patients. CONCLUSION: Osmophobia appears structurally
      integrated into the migraine history of the patient; however, for differential
      diagnosis with ETTH, other criteria are necessary.

PMID- 28503500
TI  - The Correlation between Different Risk Factors of Hepatitis C and Different
      Genotypes.
AB  - BACKGROUND: Hepatitis C infection is one of the health problems in the world.
      Several known risk factors are responsible in transmission of this infection. We
      are going to study the prevalence of these risk factors for different genotypes
      of hepatitis C and if possible, specify probable relations between each risk
      factor and transmission of each genotype. MATERIALS AND METHODS: This is a cross
      sectional study done on 270 people who had positive anti-hepatitis C virus (HCV)
      antibody and HCV RNA. Demographic specificity and possible risk factors were
      collected using a questionnaire, and statistical analysis was done by SPSS
      software (version 20). Chi-square test used to estimate the prevalence and
      relation between each qualitative risk factor and HCV genotype transmitted.
      Analysis of variance was used for studying the prevalence and relation between
      quantitative risk factors and HCV genotypes. RESULTS: The sample size was 270
      persons. Of these, 217 (80.4%) were men and 185 (68.5%) were infected with
      genotype Type III. Most people were in age range of 31-40 years old 92 (34%).
      Single people were 126 (46.7%) and 169 (62.6%) were high school and university
      graduated. Tattooing as a risk factor had a meaningful relation with hepatitis C
      genotype (P < 0.001). CONCLUSIONS: According to the findings, most people in
      central provinces of Iran with hepatitis C are carrying genotype III, with most
      prevalent risk factors such as intravenous drug use and unsafe sexual activity.
      Besides, tattooing had a significant association with hepatitis C genotype, so
      that in these groups of people, genotype I was more frequent isolated virus.

PMID- 28503501
TI  - Acute Subdural Hematoma and Subarachnoid Hemorrhage Caused by Ruptured Cortical
      Artery Aneurysm: Case Report and Review of Literature.
AB  - The present report describes an acute subdural hematoma (ASDH) associated with
      subarachnoid hemorrhage (SAH), due to ruptured cortical aneurysm. To our
      knowledge, extremely rare cases of this sort have been reported so far. A 23-year
      old male patient without previous trauma presented with severe headache and
      rapidly decreasing level of consciousness to decerebrate status. Computed
      tomography (CT) scan has demonstrated an ASDH together with SAH. Hematoma has
      immediately been evacuated without any evaluation by angiography. After
      evacuation of the thick subdural clot, a 10-mm aneurysm was revealed on a
      precentral artery of frontal cortex, which was ligated. However, after 35 days
      the patient discharged with left side hemiparesis and dysphasia, and just after
      several months of admission he got symptom free. Ruptured cortical aneurysm
      should be considered as one of the causes of spontaneous ASDH. Vascular anomaly
      investigations are suggested for these cases, thus CT angiography or digital
      subtraction angiography has to be considered if clinical condition allows.

PMID- 28503502
TI  - Prevalence of Nonalcoholic Fatty Liver Disease and its Related Metabolic Risk
      Factors in Isfahan, Iran.
AB  - BACKGROUND: This study aimed to determine the prevalence of nonalcoholic fatty
      liver disease (NAFLD) and its related risk factors among the general population
      of Isfahan city located in the central part of Iran. MATERIALS AND METHODS: In
      this cross-sectional study, the prevalence of NAFLD among 483 general adult
      populations was determined using ultrasonography. Anthropometric and biochemical
      variables were compared in groups with and without NAFLD and their predictive
      value for occurrence of NAFLD was investigated also. RESULTS: Prevalence of NAFLD
      was 39.3%. Frequency of focal fatty infiltration (FFI), Grade I, Grade II, and
      Grade III of NAFLD was 9.5%, 21.1%, 7.2%, 1.4%, respectively. Prevalence of
      different types of NAFLD and FFI, was not different between female and male
      participants (P = 0.238). Ordinal regression was determined that all of the
      studied variables have significant predictive value for NAFLD (P < 0.001, gamma =
      0.615). Spearman correlation indicated that there was a significant relationship
      between NAFLD and BMI (r = 0.37, P < 0.001), age (r = 0.15, P = 0.001), FBS (r =
      0.20, P < 0.001), cholesterol (r = 0.19, P < 0.001), triglyceride (r = 0.20, P <
      0.001), LDL (r = 0.16, P < 0.001), AST (r = 0.17, P < 0.001), and ALT (r = 0.31,
      P < 0.001). CONCLUSIONS: Considering the high prevalence of NAFLD specially its
      lower grades among Isfahani adult general population and their association with
      studied variables, it seems that interventional studies which target-related
      mentioned risk factors could reduce the overall occurrence of NAFLD.

PMID- 28503503
TI  - Measurement Methods for Physical Activity and Energy Expenditure: a Review.
AB  - Physical activity is defined as any bodily movement produced by skeletal muscles
      that results in energy expenditure. The benefits of physical activity for health
      maintenance have been well documented, especially in the prevention and
      management of chronic diseases. Therefore, accurate measurement of physical
      activity and energy expenditure is essential both for epidemiological studies and
      in the clinical context. Given the large number of available methods, it is
      important to have an understanding of each, especially when one needs to choose a
      technique to use. The purpose of this review was to discuss the components of
      total energy expenditure and present advantage and limitations of different
      methods of physical activity and energy expenditure assessment.

PMID- 28503504
TI  - Antioxidant Status and Risk of Gestational Diabetes Mellitus: a Case-Control
      Study.
AB  - Gestational diabetes mellitus (GDM) is described as glucose intolerance diagnosed
      during pregnancy. Increased oxidative stress has implicated in diabetic problems.
      The aim of the current study was to compare antioxidant capacity and antioxidant
      nutrient intake between women with GDM (n = 40) and healthy pregnant women (n =
      40). Demographic and obstetrics data were completed using interview technique and
      dietary intakes by using a semi-quantitative food frequency questionnaire (FFQ)
      with 168 items. The total antioxidant capacity (TAC) of serum was assessed by
      double-antibody sandwich enzyme-linked immune-sorbent assay (ELISA) method.
      Multivariate logistic regression was performed to compare independent variables
      and other potential risk factors between 2 groups. The results showed that TAC
      concentration of serum in women with GDM was significantly lower than in healthy
      pregnant women (2.3 +/- 0.7 vs. 3.7 +/- 0.1 umol/L, p < 0.001). Intakes of
      vitamin E (11.8 + 3.1 vs. 16.2 + 3.1 mg, p < 0.001), selenium (81 +/- 26 vs. 95
      +/- 36 ug, p < 0.05) and zinc (7.4 +/- 1.9 vs. 9.1 +/- 1.7 mg, p < 0.001) were
      significantly lower in women with GDM as compared to healthy pregnant women. In
      contrast, the groups showed no significant difference in vitamin C, beta
      carotene, selenium, fruit, and vegetable intake. Our findings showed that
      antioxidant capacity is lower in women with GDM, possibly related to lower
      intakes of vitamin E and zinc.

PMID- 28503505
TI  - Depression Is a Mediator for the Relationship between Physical Symptom and
      Psychological Well-being in Obese People.
AB  - This present study aimed to investigate the association effect of obesity status,
      physical symptom, insecure attachment, and depression on psychological well-being
      in non-diabetic healthy Koreans. Height, weight, waist circumference, blood
      pressure, and socio-psychological questionnaires (insecure attachment,
      depression, and physical symptom psychological well-being, etc.) were examined in
      123 healthy Koreans. Student t-test, correlation analysis, and mediation analysis
      were performed. Study subjects were divided into 2 groups based on body mass
      index (BMI, kg/m2): obesity (BMI >= 25, n = 36) and non-obesity (BMI < 25, n =
      87). Obese people were older and showed higher proportion of males than non-obese
      ones. Regarding the values of socio-psychological test, obesity group showed
      lower insecure attachment, and higher physical symptom than non-obesity group. In
      correlation and mediation analyses, depression was positively related to insecure
      attachment and physical symptom in both BMI groups. Positive relationship between
      physical symptom and insecure attachment was observed only in non-obesity group,
      but not in obesity group. The effect of insecure attachment on psychological well
      being was completely mediated by depression in both BMI groups. On the other
      hand, the effect of physical symptom on psychological well-being was completely
      mediated by depression in obesity group, but not in non-obesity group. In
      conclusion, this study presented that the effects of physical symptom and
      insecure attachment on psychological well-being were completely mediated by
      depression in obese healthy Koreans, but not in non-obese ones. It will provide
      useful data for extending the knowledge on the relationship between the physical
      health and mental health.

PMID- 28503506
TI  - Applicability Evaluation of Job Standards for Diabetes Nutritional Management by
      Clinical Dietitian.
AB  - This study was conducted to evaluate applicability of job standards for diabetes
      nutrition management by hospital clinical dietitians. In order to promote the
      clinical nutrition services, it is necessary to present job standards of clinical
      dietitian and to actively apply these standardized tasks to the medical
      institution sites. The job standard of clinical dietitians for diabetic nutrition
      management was distributed to hospitals over 300 beds. Questionnaire was
      collected from 96 clinical dietitians of 40 tertiary hospitals, 47 general
      hospitals, and 9 hospitals. Based on each 5-point scale, the importance of
      overall duty was 4.4 +/- 0.5, performance was 3.6 +/- 0.8, and difficulty was 3.1
      +/- 0.7. 'Nutrition intervention' was 4.5 +/- 0.5 for task importance, 'nutrition
      assessment' was 4.0 +/- 0.7 for performance, and 'nutrition diagnosis' was 3.4 +/
      0.9 for difficulty. These 3 items were high in each category. Based on the grid
      diagram, the tasks of both high importance and high performance were 'checking
      basic information,' 'checking medical history and therapy plan,' 'decision of
      nutritional needs,' 'supply of foods and nutrients,' and 'education of nutrition
      and self-management.' The tasks with high importance but low performance were
      'derivation of nutrition diagnosis,' 'planning of nutrition intervention,'
      'monitoring of nutrition intervention process.' The tasks of both high importance
      and high difficulty were 'derivation of nutrition diagnosis,' 'planning of
      nutrition intervention,' 'supply of foods and nutrients,' 'education of nutrition
      and self-management,' and 'monitoring of nutrition intervention process.' The
      tasks of both high performance and high difficulty were 'documentation of
      nutrition assessment,' 'supply of foods and nutrients,' and 'education of
      nutrition and self-management.'

PMID- 28503507
TI  - Nutritional Status of Korean Children and Adolescents with Attention Deficit
      Hyperactivity Disorder (ADHD).
AB  - Attention deficit hyperactivity disorder (ADHD) has been associated with an
      elevated risk for obesity but this seems to be paradoxical to the fact that many
      youths with ADHD have symptoms of hyperactivity. People diagnosed with ADHD tend
      to have a high risk of developing undesirable diet habits and consequently have
      health related problems. However, less attention has been paid to obesity in ADHD
      while many efforts have been devoted to the prevention of childhood obesity in
      mentally normal people. Hence the purpose of this study was to explore the
      nutritional status and life habits of children and adolescents with ADHD (n = 76)
      based on degree of obesity by utilizing the Korean National Health and Nutrition
      Examination Survey (KNHANES) data from 2005-2013. As results the levels of blood
      pressure, total triglycerides and the fat intake relative to total energy intake
      in overweight ADHD group were higher than those in normal weight group.
      Interestingly, overweight ADHD subjects consumed significantly less amount of
      iron compared to normal weight ADHD subjects and the level of serum ferritin was
      lower in the overweight ADHD group (59.0 ng/mL) than in the normal weight ADHD
      group (47.9 ng/mL). After adjusting total energy intake, total vegetable
      consumption was 14.3% lower in overweight group compared to the consumption in
      normal weight group. These results indicate a plausible relationship of iron
      status and obesity in ADHD subjects but this relationship may not be specific to
      ADHD. A future study with case-control design is necessary to investigate the
      association of obesity, nutrient intake, and cognitive/mental status of ADHD.

PMID- 28503509
TI  - Nicotinamide Reduces Amyloid Precursor Protein and Presenilin 1 in Brain Tissues
      of Amyloid Beta-Tail Vein Injected Mice.
AB  - The purpose of this study is to investigate whether nicotinic acid (NA) and
      nicotinamide (NAM) reduce the Alzheimer disease (AD)-related gene expression in
      brain tissues of amyloid beta (Abeta)-injected mice. Male Crj:CD1 (ICR) mice were
      divided into 6 treatment groups; 1) control, 2) Abeta control, 3) Abeta + NA 20
      mg/kg/day (NA20), 4) Abeta + NA40, 5) Abeta + NAM 200 mg/kg/day (NAM200), and 6)
      Abeta + NAM400. After 1-week acclimation period, the mice orally received NA or
      NAM once a day for a total of 7 successive days. On day 7, biotinylated Abeta42
      was injected into mouse tail vein. At 5 hours after the injection, blood and
      tissues were collected. Abeta42 injection was confirmed by Western blot analysis
      of Abeta42 protein in brain tissue. NAM400 pre-treatment significantly reduced
      the gene expression of amyloid precursor protein and presenilin 1 in brain
      tissues. And, NAM200 and NAM400 pre-treatments significantly increased sirtuin 1
      expression in brain tissues, which is accompanied by the decreased brain
      expression of nuclear factor kappa B by 2 doses of NAM. Increased expression of
      AD-related genes was attenuated by the NAM treatment, which suggests that NAM
      supplementation may be a potential preventive strategy against AD-related
      deleterious changes.

PMID- 28503508
TI  - Carbohydrate Composition Associated with the 2-Year Incidence of Metabolic
      Syndrome in Korean Adults.
AB  - The aim of this study was to investigate the association between macronutrient
      composition and metabolic syndrome (MetS) incidence in Korean adults. Data were
      obtained from a cohort of 10,030 members aged 40 to 69 years who were enrolled
      from the 2 cities (Ansung and Ansan) between 2001 and 2002 to participate in the
      Korean Genome Epidemiology Study. Of these members, 5,565 participants, who were
      free of MetS and reported no diagnosis of cardiovascular disease at baseline,
      were included in this study. MetS was defined using the criteria of the National
      Cholesterol Education Program-Adult Treatment Panel III and Asia-Pacific criteria
      for waist circumference. MetS incidence rate were identified during a 2-year
      follow-up period. Baseline dietary information was obtained using a semi
      quantitative food frequency questionnaire. Multivariate logistic regression
      analysis was used to evaluate the association between the quartiles of
      percentages of total calorie from macronutrients consumed and MetS incidence. In
      analyses, baseline information, including age, sex, body mass index, income
      status, educational status, smoking status, alcohol drinking status, and physical
      activity level was considered as confounding variables. Participants with the
      second quartile of the percentages of carbohydrate calorie (67%-70%) had a 23%
      reduced odds ratio (95% confidence interval, 0.61-0.97) for MetS incidence
      compared with those with the fourth quartile after adjusting for confounding
      variables. The findings suggest that middle aged or elderly Korean adults who
      consume approximately 67%-70% of calorie from carbohydrate have a reduced risk of
      MetS.

PMID- 28503511
TI  - Erratum: Dietary Antioxidant Capacity and Its Association with Preeclampsia.
AB  - [This corrects the article on p. 47 in vol. 6, PMID: 28168181.].

PMID- 28503510
TI  - A Case Report of the Nutrition Support for a Patient with HELLP Syndrome.
AB  - A 30-year-old female patient, 18 weeks gestational age, with no prior medical
      history was admitted to hospital complaining severe right upper quadrant pain.
      The patient was admitted to intensive care unit (ICU) after emergency surgery to
      treat intraperitoneal hemorrhage caused by rupture of liver hematoma. Despite the
      absence of high blood pressure, the patient was diagnosed with hemolysis,
      elevated liver enzymes, and low platelet count (HELLP) syndrome on the basis of
      abnormal levels of blood aspartate aminotransferase/alanine aminotransferase,
      lactate dehydrogenase, total bilirubin, direct bilirubin, C-reactive protein
      (CRP) and platelet along with liver damage and proteinuria. While in ICU, the
      patient was given total parenteral nutrition (TPN) and enteral nutrition (EN) for
      -20 days because oral feeding was impractical. In the early stage, TPN supply was
      not sufficient to meet the elevated nutritional demand induced by disease and
      surgery. Nevertheless, continuous care of nutrition support team enabled
      satisfactory EN and, subsequently, oral feeding which led to improvement in
      patient outcome.

PMID- 28503512
TI  - Analysis of Nested Case-Control Study Designs: Revisiting the Inverse Probability
      Weighting Method.
AB  - In nested case-control studies, the most common way to make inference under a
      proportional hazards model is the conditional logistic approach of Thomas (1977).
      Inclusion probability methods are more efficient than the conditional logistic
      approach of Thomas; however, the epidemiology research community has not accepted
      the methods as a replacement of the Thomas' method. This paper promotes the
      inverse probability weighting method originally proposed by Samuelsen (1997) in
      combination with an approximate jackknife standard error that can be easily
      computed using existing software. Simulation studies demonstrate that this
      approach yields valid type 1 errors and greater powers than the conditional
      logistic approach in nested case-control designs across various sample sizes and
      magnitudes of the hazard ratios. A generalization of the method is also made to
      incorporate additional matching and the stratified Cox model. The proposed method
      is illustrated with data from a cohort of children with Wilm's tumor to study the
      association between histological signatures and relapses.

PMID- 28503513
TI  - Transanal Minimally Invasive Surgery After Chemoradiotherapy: Widening Scope of
      Indications for Local Excision.

PMID- 28503514
TI  - Mucinous Subtype in Patients With Colorectal Cancer.

PMID- 28503515
TI  - Synthetic Versus Biological Mesh-Related Erosion After Laparoscopic Ventral Mesh
      Rectopexy: A Systematic Review.
AB  - PURPOSE: This review reports the incidence of mesh-related erosion after ventral
      mesh rectopexy to determine whether any difference exists in the erosion rate
      between synthetic and biological mesh. METHODS: A systematic search of the
      MEDLINE and the Ovid databases was conducted to identify suitable articles
      published between 2004 and 2015. The search strategy capture terms were
      laparoscopic ventral mesh rectopexy, laparoscopic anterior rectopexy, robotic
      ventral rectopexy, and robotic anterior rectopexy. RESULTS: Eight studies (3,956
      patients) were included in this review. Of those patients, 3,517 patients
      underwent laparoscopic ventral rectopexy (LVR) using synthetic mesh and 439 using
      biological mesh. Sixty-six erosions were observed with synthetic mesh (26 rectal,
      32 vaginal, 8 recto-vaginal fistulae) and one (perineal erosion) with biological
      mesh. The synthetic and the biological mesh-related erosion rates were 1.87% and
      0.22%, respectively. The time between rectopexy and diagnosis of mesh erosion
      ranged from 1.7 to 124 months. No mesh-related mortalities were reported.
      CONCLUSION: The incidence of mesh-related erosion after LVR is low and is more
      common after the placement of synthetic mesh. The use of biological mesh for LVR
      seems to be a safer option; however, large, multicenter, randomized, control
      trials with long follow-ups are required if a definitive answer is to be
      obtained.

PMID- 28503516
TI  - Transanal Minimally-Invasive Surgery for Treating Patients With Regressed Rectal
      Cancer After Preoperative Chemoradiotherapy.
AB  - PURPOSE: Although the standard treatment for patients with locally advanced
      rectal cancer managed by preoperative chemoradiotherapy (CRT) is a radical
      resection, local excisions are used in highly-selective cases. Recently,
      transanal minimally-invasive surgery (TAMIS) has emerged as a feasible technique
      for local excision of midrectal lesions. We assess the feasibility of using TAMIS
      to treat patients with locally advanced rectal cancer who showed good response to
      CRT. METHODS: From October 2010 to June 2013, 35 consecutive patients with rectal
      cancer managed by using preoperative CRT underwent TAMIS. After a single-incision
      laparoscopic surgery port had been introduced into the anal canal, a full
      thickness local excision with conventional laparoscopic instruments was
      performed. We retrospectively reviewed a prospectively collected database of
      these cases. RESULTS: Of the 35 patients analyzed, 18 showed pathologic complete
      responses and 17 had residual lesions (2 ypTis, 4 ypT1, 9 ypT2, and 2 ypT3); 34
      (97.1%) showed clear deep, lateral margins. The median distance of lesions from
      the anal verge was 5 cm. All procedures were completed laparoscopically, and the
      median operating time was 84 minutes. No intraoperative events or morbidities
      were seen in any of the patients, except one with wound dehiscence, who was
      treated conservatively. The median postoperative hospital stay and follow-up
      period were 4 days and 36 months, respectively. During the study period, no
      patients died, but 5 (14.3%) experienced recurrence, including one recurrence at
      the TAMIS site. CONCLUSION: TAMIS seems to be a feasible, safe modality for
      treating patients with locally advanced rectal cancer who show good response to
      preoperative CRT.

PMID- 28503517
TI  - Prognostic Significance of Mucinous Histologic Subtype on Oncologic Outcomes in
      Patients With Colorectal Cancer.
AB  - PURPOSE: Mucinous adenocarcinomas account for about 10% of all colorectal
      cancers. This study aimed to investigate the prognostic impact of mucinous
      histologic subtype on oncologic outcomes in patients with colorectal cancer.
      METHODS: This retrospective study was performed at two large tertiary university
      hospitals. We analyzed the characteristics, prognostic factors, and survival of
      patients with colorectal cancer who were treated and followed up between 2000 and
      2013. RESULTS: Totally, 144 of 1,268 patients with a colorectal adenocarcinoma
      (11.4%) had mucinous histologic subtype. Statistically significant results found
      in this research are as follows: Mucinous histologic subtype tended to present in
      younger patients and to have larger tumor size, higher histologic grade, higher
      node stage, larger number of positive nodes, and higher rate of perineural
      invasion compared to nonmucinous histologic subtype. On the univariate analysis,
      mucinous subtype was a prognostic factor for disease-free and overall survival.
      On the multivariate analysis, primary tumor location, node stage and lymphatic
      vascular invasion were independent prognostic factors for the local control rate.
      Rectal tumor location, higher disease stage, tumor grade II, and presence of
      lymphatic-vascular invasion had negative influences on disease-free survival, as
      did rectal tumor location, higher disease stage and presence of lymphatic
      vascular invasion on overall survival. CONCLUSION: Mucinous histologic subtype
      was associated with some adverse pathologic features in patients with colorectal
      cancer; however, it was not an independent prognostic factor for oncologic
      outcome.

PMID- 28503518
TI  - Laparoscopic Vaginal Suspension and Rectopexy for Rectal Prolapse.
AB  - PURPOSE: Laparoscopic procedures for the treatment of patients with a rectal
      prolapse have gained increasing worldwide acceptance because they have lower
      recurrence and better functional outcome than perineal procedures. Nevertheless,
      ideal surgical methods are still not available. We propose a new surgical
      technique, laparoscopic vaginal suspension and rectopexy, for correcting a full
      thickness rectal prolapse and/or middle-compartment prolapse. This study assessed
      the short-term outcomes for patients who underwent laparoscopic vaginal
      suspension and rectopexy. METHODS: Between April 2014 and April 2016, 69 female
      patients underwent laparoscopic vaginal suspension and rectopexy to correct a
      rectal prolapse. Demographics, medical histories, and surgical and follow-up
      details were collected from their medical records. In addition to the clinical
      outcome, we repeated defecation proctography and a questionnaire regarding
      functional results three months after surgery. RESULTS: No major morbidities or
      no mortalities occurred. The defecation proctography confirmed excellent
      anatomical result in all cases. Of 7 patients with combined middle-compartment
      prolapses, we observed good anatomical correction. During follow-up, full
      thickness recurrence occurred in one patient. Preoperative fecal incontinence was
      improved significantly at 3 months (mean Wexner score: 12.35 vs. 7.71; mean FISI:
      33.29 vs. 21.07; P < 0.001). Analysis of responses to the fecal incontinence
      quality of life (FIQOL) questionnaire showed overall improvement at 3 months
      compared to the preoperative baseline (mean pre- and postoperative FIQOL scores:
      12.11 vs. 14.39; P < 0.004). CONCLUSION: Laparoscopic vaginal suspension and
      rectopexy is a new combined procedure for the treatment of patients with rectal
      prolapses. It has excellent functional outcomes and minimal morbidity and can
      correct and prevent middlecompartment prolapses.

PMID- 28503521
TI  - Can exercise rehabilitation evolve into a new therapeutic area?

PMID- 28503520
TI  - Pulmonary Sarcoidosis That Developed During the Treatment of a Patient With Crohn
      Disease by Using Infliximab.
AB  - For inflammatory bowel disease (IBD), antitumor necrosis factor treatment offers
      a new direction for both patients and medical doctors. This treatment has
      dramatically improved the quality of life for patients with ulcerative colitis
      and Crohn disease (CD). However, with increasing usage and longer follow-up
      periods, a wider range of possible adverse effects may be encountered. We report
      an unusual case of pulmonary sarcoidosis developed during the treatment of a
      patient with CD by using infliximab. A 30-year-old male who had been treated for
      CD with infliximab for 18 months was admitted due to abnormal opacities on chest
      radiography. Chest computed tomography displayed clustered small nodules in both
      lobes and enlarged multiple lymph nodes. The patient was diagnosed with
      sarcoidosis from the results of a biopsy of the subcarinal lymph node. Lung
      lesions were improved five months after infliximab was stopped.

PMID- 28503519
TI  - Multiple Myeloma Mimics Bone Metastasis From a Rectal Adenocarcinoma.
AB  - A presumptive diagnosis of bone metastasis can be easily made when a patient with
      a history of colorectal cancer develops bone lesions that are seen on follow-up
      imaging. In this case report, we describe a patient whose multiple bone lesions
      were wrongly attributed to a recurrence of rectal cancer rather than being
      identified as multiple myeloma lesions. When clinicians detect new, abnormal,
      bony lesions in a patient with a previous history of cancer, they should consider
      diseases such as multiple myeloma in their differential diagnosis.

PMID- 28503522
TI  - Treadmill exercise alleviates depressive symptoms in rotenone-induced Parkinson
      disease rats.
AB  - Parkinson disease (PD) is characterized by selective loss of the dopaminergic
      neurons. The symptoms of depression following PD are closely associated with
      reduced activity of the serotonergic system in the dorsal raphe. We explored the
      antidepressive effect of exercise and its possible mechanism using the rotenone
      induced PD rats. PD rats were induced by subcutaneously injection with rotenone
      for 14 days. The rats in the exercise groups were made to run on a treadmill for
      30 min once a day during 14 consecutive days. Forced swimming test,
      immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT), tryptophan
      hydroxylase (TPH), and western blot for serotonin 1A (5-HT1A) receptor were
      conducted. Injection of rotenone induced PD rats. PD rats showed depressive state
      and treadmill exercise ameliorated this depressive state. 5-HT, TPH, and 5-HT1A
      receptor expressions in the dorsal raphe were suppressed by rotenone injection
      and treadmill exercise increased the expressions of 5-HT, TPH, and 5-HT1A
      receptor in the rotenone-injected rats. The present results show that treadmill
      exercise ameliorated depressive symptoms in the rotenone-induced PD rats. The
      antidepressive effect of treadmill exercise might be ascribed to the enhancement
      of serotonergic function through upregulation of 5-HT1A expression in the dorsal
      raphe.

PMID- 28503523
TI  - Treadmill exercise ameliorates depressive symptoms through increasing serotonin
      expression in postpartum depression rats.
AB  - Postpartum depression (PPD) is defined as the depressive symptoms that occur from
      the moment of delivery until 12 months after delivery. PPD symptoms are closely
      associated with reduced activity of the serotonergic system. Serotonin (5
      hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of
      depression. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step of 5-HT
      biosynthesis in the serotonergic neurons. Exercise exerts anti-depressive effect
      on depression patients as well as on animal models of depression. In the present
      study, the effect of treadmill exercise on PPD was investigated using rats. For
      this study, open field test for activity and forced swimming test for depressive
      symptoms, and immunohistochemistry for 5-HT and TPH were conducted. The rats in
      the exercise groups were forced to run on a motorized treadmill for 30 min once a
      day for 2 weeks. Activity in the open field test was decreased in the postpartum
      rats, however, performing treadmill running increased activity in the postpartum
      rats. The climbing time was decreased and the immobility time was increased in
      the postpartum rats. Treadmill exercise increased climbing time and suppressed
      immobility time in the postpartum rats. 5-HT and TPH expressions in the dorsal
      raphe were suppressed in the postpartum rats, and treadmill exercise enhanced 5
      HT and TPH expressions in the postpartum rats. Treadmill exercise ameliorated the
      PPD very effectively by enhancing serotonin level.

PMID- 28503524
TI  - Treadmill exercise improves motor and memory functions in cerebral palsy rats
      through activation of PI3K-Akt pathway.
AB  - Cerebral palsy (CP) is a chronic disorder characterized by physical disability
      and disruption of brain function. We evaluated the effects of treadmill exercise
      on motor and memory functions in relation with phosphatidylinositol 3-kinase
      (PI3K)-Akt pathway using CP rat model. Rota-rod test, step-down avoidance task, 5
      bromo-2'-deoxyuridine (BrdU) immunohistochemistry, and western blot for synapsin
      I, postsynaptic density-95 (PSD-95), PI3K, Akt, and glycogen synthase kinase
      3beta (GSK-3beta) were performed. CP was induced by maternal lipopolysaccharide
      (LPS)-injection with sensorimotor restriction. Five weeks after birth, the rats
      in the exercise groups were made to run on the treadmill for 30 min per one day,
      5 times a week, during 4 weeks. Motor and memory functions were impaired in the
      LPS-induced CP rats and tread-mill exercise increased motor and memory functions
      in the CP rats. Cell proliferation in the hippocampus was suppressed in the LPS
      induced CP rats and treadmill exercise increased hippocampal cell proliferation
      in the CP rats. Expressions of synapsin I, PSD-95, phosphorylated (p)-PI3K, and p
      Akt were decreased in the LPS-induced CP rats and treadmill exercise enhanced the
      expressions of synapsin I, PSD-95, p-PI3K, and p-Akt in the CP rats. GSK-3beta
      expression was increased in the LPS-induced CP rats and treadmill exercise
      suppressed GSK-3beta expression in the CP rats. The present results suggest that
      treadmill exercise might improve motor and memory functions through activation of
      PI3K-Akt pathway.

PMID- 28503525
TI  - Study on emotion by rest time in mice with repetitive sleep deprivation.
AB  - Sleep deprivation (SD) inhibits normal biorhythms, causing physical and mental
      problems. To solve the problems caused by SD, fundamental measures are needed. I
      investigated change of recovery by rest time in psychological aspect after
      repetitive SD. The mice were divided into four groups: control 24-hr rest after
      24-hr SD group, 48-hr rest after 24-hr SD group, and 72-hr rest after 24-hr SD
      group (n=20 in each group). I carried out SD in the water cage included multiple
      platforms. Repetitive SD executes for 36 days. I measured weight every week after
      SD for 6 weeks. To check emotional condition, I carried out intruder-evoked
      aggression test and modified forced swimming test. In the present results, group
      treated 24-hr rest and 48-hr rest after 24-hr SD showed lower natural
      aggressiveness and high depression. However, group treated 72-hr rest after 24-hr
      SD indicated emotional changes to recover the normal conditions. In the weight
      change, all group showed significant decrease compared to control for 6 weeks. I
      suggest that appropriate rest time after SD can help to restore emotional change.

PMID- 28503526
TI  - Be seeded or not be seeded? A study with Olympic judo athletes.
AB  - The main purpose of the present study was to calculate the probability-based on a
      Bayesian approach-to win a medal in the Olympic Games given the athlete is seeded
      and to verify if the number one ranked athlete has any advantage compared to
      other seeded athletes concerning his/her chances to be Olympic champion. For
      this, data from athletes who took part in the London 2012 and Rio 2016 Olympic
      Games were considered. For males the probability of seeded athletes to win a
      medal was 41.1% and 42.9%, while for females it was 35.7% and 44.6% at London
      2012 and Rio 2016, respectively. Furthermore, the probability of athletes ranked
      as number one to become Olympic champion among the seeded athletes was 19.5% and
      36.8% for males and 32.3% and 36.8% for females in London 2012 and Rio 2016,
      respectively. Based on these results the cost-benefit of investing human and
      financial resources to qualify an athletes among the top eight competitors and
      his/her exposure to competitions-resulting in technical-tactical analysis of the
      opponent and higher risk of injury-should be carefully analyzed when determining
      the competition calendar to each athlete.

PMID- 28503527
TI  - Postactivation potentiation in elite young soccer players.
AB  - The aim of this study was to investigate the acute effects of 16 different
      combinations to cause the postactivation potentiation (PAP) in elite young soccer
      players. Squat exercise in 4 different intensities (40%, 60%, 80%, and 100% one
      repetition maximum [1RM]) was performed and its effects were evaluated in the
      performance of countermovement jump (CMJ), after 4 different recovery times (1,
      3, 5, and 10 min). For this purpose, 25 young soccer players, underwent five
      experimental sessions. At the first session the control to determine 1RM in half
      squat was carried out. The following four experimental sessions were comprised of
      four intensity combinations with four different recovery intervals in order to
      perform the CMJ test later, randomly determined and with 30-min interval between
      each combination. The conditions were compared using an analysis of variance with
      repeated measurements, followed by Bonferroni test, using 5% significance level
      (P<0.05). The different intensities investigated did not provide significant
      increases in CMJ height, but significant differences were noted in recovery time,
      where, at CMJ maximum height, 1-min interval was better than after 3 min
      (P<0.05), 5, and 10 min (P<0.001). On the average jump performances, 1-min
      interval resulted in better results (P<0.001) compared to other intervals. The 10
      min recovery resulted in poorer performances compared to the other intervals
      (P<0.001). Our results indicate that regardless the intensity used in the half
      squat exercise with elite young soccer players, the 1-min recovery time was more
      appropriate to promote an increase in vertical jump.

PMID- 28503528
TI  - The development of anger management program based on acceptance and commitment
      therapy for youth taekwondo players.
AB  - This study aimed to develop an intervention program based on acceptance and
      commitment therapy (ACT) for youth taekwondo players. Eight sessions of the ACT
      program were provided to nine youth taekwondo players. The content analysis was
      conducted for the activities, activity sheets, assignments, and program
      evaluations. First of all, the results showed that the ACT program changed the
      participants' diverse psychological inflexibility a flexible and value-oriented
      state, which was supported by their positive mood changes after each session.
      Secondly, 'walking meditation,' 'a bus driver and a passenger role play,' and
      'writing a letter to the self' were positively evaluated according to the
      analysis on the feedbacks and evaluations on each session and activity. Lastly,
      overall evaluation on the ACT program indicated that there were changes in a
      positive attitude, thoughts, and feelings (anger and irritation) toward
      taekwondo. The most memorable activities were 'eating meditation,' 'breath
      counting meditation,' and 'welcoming the beggar' exercise. These results suggest
      that an intervention program based on the ACT may have a positive impact on anger
      management for youth.

PMID- 28503530
TI  - Caffeine supplementation affects the immunometabolic response to concurrent
      training.
AB  - The aim of the present study was to investigate the effects of caffeine (CAF) and
      carbohydrate (CHO) intake on strength performance and its metabolic and
      inflammatory responses during concurrent training. Seven active males ingested a
      double-placebo (P), CAF (capsule 5 mg/kg) or CHO (20% maltodextrin solution)
      supplementation before strength exercise. Participants performed three randomized
      sessions of 5,000-m high-intensity intermittent aerobic exercise at maximal
      intensity followed by strength exercise, performing after the P, CHO, and CAF
      intake. The blood samples were collected before (pre) and immediately after
      concurrent strength exercise (post). We found a similar number of repetitions and
      total volume in all supplementation groups. There was a main effect of time on
      glucose, lactate, and interleukin (IL)-6 (P<0.05). When compared the changes
      between groups (postvalues minus prevalues), there was lower glucose in CAF group
      when compared to CHO group (CAF= 5.0+/-10.4 vs. CHO=27.8+/-20 vs. P=15.1+/-14,
      P=0.031) and higher IL-6 levels (CAF=11.9+/-9.2 vs. CHO=-2.4+/-1.7 vs. P=4.3+/-
      11.7, P=0.017). There was significant interaction for glucose and lactate
      (P<0.001). In conclusion, CAF and CHO intake did not improve strength performance
      during concurrent strength training in active males. However, CAF affected
      immunometabolic responses.

PMID- 28503531
TI  - Relationship between cardiopulmonary responses and isokinetic moments: the
      optimal angular velocity for muscular endurance.
AB  - Most protocols for testing and rehabilitation for recovery and improvement of
      muscular endurance have been set at 180 degrees /sec, 240 degrees /sec, and 300
      degrees /sec. These protocols can cause confusion to clinical providers or other
      researchers. This study was aimed at investigating the optimal isokinetic angular
      speed for measuring or developing muscular endurance after assessing the
      relationship between cardiopulmonary responses and isokinetic moments. This study
      was conducted with 31 male and female college students. Graded exercise test and
      body composition were measured as well as the isokinetic moments of the knee
      muscles at three angular speeds: 180 degrees /sec, 240 degrees /sec, and 300
      degrees /sec. The specific isokinetic moments of knee muscles that were measured
      included: peak torque (PT) and total work (TW) on extensor (e) and flexor (f) of
      knee joints, which were denoted as ePT180, fPT180, eTW180, fTW180, ePT240,
      fPT240, eTW240, fTW240, ePT300, fPT300, eTW300, and fTW300 according to the three
      angular speeds. Spearman correlation test was used to examine the relationship
      between the sum means of cardiopulmonary responses and the variables of
      isokinetic moments. This study confirmed that the optimal angular speed for
      testing or training for muscular endurance was 180 degrees /sec, which showed a
      stronger relationship between cardiopulmonary responses and isokinetic moments.
      Therefore, this angular speed is recommended for testing and training for
      muscular endurance of the knee joints.

PMID- 28503529
TI  - Regular physical education class enhances sociality and physical fitness while
      reducing psychological problems in children of multicultural families.
AB  - This study investigated the influence of physical education class (PEC) as an
      intervention method for aggression, sociality, stress, and physical fitness
      levels in children from multicultural families. The hypothesis was that
      participating in PEC would result in reduced aggression and stress and improved
      sociality and physical fitness in multicultural children. A three-item
      questionnaire, a body composition test, and physical fitness tests were given
      three times. Eighty-four subjects were divided into four groups: multicultural
      children who participated in PEC (multi-PEG, n=12), multicultural children who
      did not participate in PEC (multi-NPEG, n=13), single-cultural children who
      participated in PEC (sing-PEG, n=11), and single-cultural children who did not
      participate in PEC (sing-NPEG, n=12), respectively. Parametric and nonparametric
      statistical methods were conducted on the collected data with a significance
      level set a priori at P<0.05. After 8 weeks of PEC, fat mass (F=2.966, P=0.045)
      and body mass index (F=3.654, P=0.021) had significantly different interaction
      effects. In the aspect of interaction effects from physical fitness variables,
      cardiopulmonary endurance (F=21.961, P=0.001), flexibility (F=8.892, P=0.001),
      muscular endurance (F=31.996, P=0.001), muscular strength (F=4.570, P=0.008), and
      power (F=24.479, P=0.001) were significantly improved in the multi-PEG compared
      to those of the other three groups. Moreover, sociality (F=22.144, P=0.001) in
      the multi-PEG was enhanced, whereas aggression (F=6.745, P=0.001) and stress
      (F=3.242, P=0.033) levels were reduced. As conclusion, the PEC reduced aggression
      and stress levels, and improved sociality and physical fitness levels after 8
      weeks. This study confirmed that PEC for children from multicultural families can
      improve psychosocial factors and physical health.

PMID- 28503532
TI  - Changes in gait kinematics and muscle activity in stroke patients wearing various
      arm slings.
AB  - Stroke patients often use various arm slings, but the effects of different slings
      on the joint kinematics and muscle activity of the arm in the gait have not been
      investigated. The effects of joint kinematics and muscle activity in the gait
      were investigated to provide suggestions for gait training for stroke patients.
      In all, 10 chronic stroke patients were voluntarily recruited. An eight-camera
      three-dimensional motion analysis system was used to measure joint kinematics
      while walking; simultaneously, electromyography data were collected for the
      anterior and posterior deltoids and latissimus dorsi. The amplitude of pelvic
      rotation on the less-affected side differed significantly among the different arm
      slings (P<0.05). Changes in the knee kinematics of the less-affected side also
      differed significantly (P<0.05), while there were no significant differences in
      the muscle activity of the affected arm. In stroke patients, an extended arm
      sling is more useful than no sling or a flexed arm sling in terms of the
      amplitude of the rotation of the less-affected pelvic side in the stance phase
      while walking. The less-affected knee joint is flexed more without a sling than
      with any sling. All arm slings support the extension of the contralateral knee.

PMID- 28503533
TI  - Effect of core strengthening with pelvic proprioceptive neuromuscular
      facilitation on trunk, balance, gait, and function in chronic stroke.
AB  - The purpose of this study was to evaluate the effects of core strengthening
      combined with pelvic proprioceptive neuromuscular facilitation (PNF) on trunk
      impairment, balance, gait, and functional ability of chronic stroke patients.
      Twenty-three participants with chronic stroke were recruited and randomly
      allocated to one of the two groups: core strengthening combined with pelvic PNF
      (group 1, n=13), and pelvic PNF with trunk flexibility exercises (group 2, n=10).
      Intervention was given to both groups for 60 min per session 5 times per week for
      4 weeks. Performance of both groups was evaluated on Trunk Impairment Scale,
      Tinetti Performance Oriented Mobility Assessment (Tinetti-POMA), Balance
      Evaluation Systems Test (Mini-BESTest), Wisconsin Gait Scale, and Barthel
      Activities of Daily Living Index prior to and after the completion of the
      intervention. The comparison between postintervention scores of Tinetti-POMA
      between group 1 (18.76+/-1.78) and group 2 (16.8+/-1.87) and Mini-BESTest group 1
      (16.15+/-1.28) and group 2 (14.7+/-1.41) showed significant difference (P=0.018).
      The results indicated that core stabilisation combined with pelvic PNF was more
      effective for improving trunk impairment, balance and gait of chronic stroke
      patients.

PMID- 28503535
TI  - Validity and reliability evidence of the physical activity level screening for
      preschoolers with developmental delays and/or disabilities.
AB  - Psychometric properties of the physical activity level screening (PALS) for
      preschoolers with a developmental delay and/or a disability were examined in this
      study. The mean age of participants (16 boys and 14 girls) was 54.9 months
      (standard deviation, 10.4). Each participant wore one Actical accelerometer and
      was filmed for 20 min during the active play time. Intrarater and interrater
      reliability, and validity of the PALS data were examined. The proportion of
      agreement for intrarater was 87.5% and 85.6% for interrater reliability.
      Intraclass correlation coefficients were 0.99 for intrarater and 0.96 for
      interrater. The PALS data showed moderate correlation with Actical data (r=0.67,
      P<0.01).

PMID- 28503534
TI  - Effects of three spinal stabilization techniques on activation and thickness of
      abdominal muscle.
AB  - In this study, we examine the thickness of the abdominal muscle and its activity
      during the performance of the three drawing-in methods. The subjects were 20
      healthy male and female students in their 20s. Using ultrasonography and
      electromyography, the experimenter measured the thickness of the transversus
      abdominis (TrA) muscle, internal oblique (IO) muscle and external oblique (EO)
      muscle. The ultrasonography measurements for the drawing-in manoeuver (DI),
      abdominal bracing, and posterior pelvic tilt (PT) techniques were 0.64+/-0.20,
      0.54+/-0.15, and 0.46+/-0.12, respectively, with significant differences for the
      TrA. The electromyography results of the DI, SA, and PT techniques were 4.35+/
      1.72, 3.00+/-1.48, and 2.70+/-1.52, respectively, for the IO. There was a
      significant difference in the DI, SA, and PT techniques for the EO (5.10+/-3.30,
      3.85+/-3.89, 2.25+/-1.29, respectively). The DI method activated the oblique
      abdominal muscles, but there was no great change in their thickness; the TrA,
      however, was selectively strengthened through changes in its thickness.

PMID- 28503536
TI  - Exercise tolerance improves after pulmonary rehabilitation in pulmonary
      hypertension patients.
AB  - Pulmonary rehabilitation (PR) is part of the recommended management plan of
      pulmonary hypertension (PHTN) and is important to better quality of life and
      exercise tolerance. This study aimed at determining effectiveness of PR on
      exercise capacity. Retrospective chart analysis was conducted on patients
      referred to our PHTN clinic for PR. Patients who had PHTN diagnosed on right
      heart catheterization (defined by mean pulmonary artery pressure>25 mmHg) and
      completed a standardized 12-week PR program were considered for the study.
      Patients' baseline exercise tolerance was recorded as speed attainable on a
      treadmill and duration of exercise in minutes. Demographics, age, sex, and oxygen
      use were obtained from chart review. Eighteen PHTN patients (5 male, 13 female;
      mean age 67.7+/-11.6 years) were considered for the study (six World Health
      Organization [WHO] group 1 pulmonary arterial hypertension [33.33%], eight WHO
      group III PHTH [44.44%], two WHO group IV and two WHO V PHTN [11.11%]). Treadmill
      speed improved following rehabilitation (1.3 mph [interquartile range {IQR}, 1.0
      1.8 mph] to 2.2 mph [IQR, 1.3-2.8 mph]; P<0.0001, Wilcoxon signed rank test).
      Median exercise time improved (27 min (IQR, 22-30 min) to 30 min (IQR, 24-30
      min); not significant. Improvement was defined only as an increase in speed or
      duration, or both. Sixteem of 18 participants improved (88.9% [95% exact binomial
      confidence interval, 65.3%-98.6%). Patients with PHTN benefit from a structured
      PR program to improve their exercise capacity and should be enrolled in PR
      programs as part of their management.

PMID- 28503537
TI  - Effects of inspiratory muscle exercise in the pulmonary function, autonomic
      modulation, and hemodynamic variables in older women with metabolic syndrome.
AB  - The aim of the present study was to investigate the effects of inspiratory muscle
      exercise (IME) on metabolic and hemodynamic parameters, cardiac autonomic
      modulation and respiratory function of older women with metabolic syndrome (MS).
      For this, sixteen older women with MS and 12 aged-matched controls participated
      of the present study. Two days before and 2 days after the main experiment,
      fasting blood samples (i.e., total cholesterol, triglycerides and blood glucose),
      cardiac autonomic modulation (i.e., heart rate variability), and respiratory
      muscle function were obtained and evaluated. The sessions of physical exercise
      was based on a IME, which was performed during 7 days. Each session of IME was
      performed during 20 min, at 30% of maximal static inspiratory pressure. In the
      results, MS group presented higher levels of triglycerides, blood glucose, and
      systolic blood pressure when compared to control group. IME was not able to
      change these variables. However, although MS group showed impaired respiratory
      muscle strength and function, as well as cardiac autonomic modulation, IME was
      able to improve these parameters. Thus, the data showed that seven days of IME
      are capable to improve respiratory function and cardiac autonomic modulation of
      older women with MS. These results indicate that IME can be a profitable therapy
      to counteracting the clinical markers of MS, once repeated sessions of acute IME
      can cause chronical alterations on respiratory function and cardiac autonomic
      modulation.

PMID- 28503538
TI  - Effects of a static stretch using a load on low back pain patients with shortened
      tensor fascia lata.
AB  - Stretch of tensor fascia lata (TFL) improves range of motion on hip and pelvis
      and it reported to help reduce low back pain. Accordingly, the purpose of this
      study was to investigate effects of static stretching using a load on TFL in
      patients with low back pain. Twenty three subjects were recruited according to
      the selection criteria. The subjects were randomly assigned to static stretching
      group (control, n=12), and a static stretching using a load group (experimental,
      n=11). All group performed stretching for 15 min (side for 50 sec per time and a
      rest for 30 sec) per day in the left side and the right, respectively, for 2
      weeks. Before and after the intervention, all groups measured visual analogue
      scale (VAS), stand and reach test, and the Oswestry disability index (ODI). In
      the present results, we found that the experimental group showed significant
      differences in VAS, stand and reach test, and the ODI (P<0.05) in before and
      after the intervention. Therefore, static stretching using a load can be actively
      utilized for low back pain patients with shortened TFL.

PMID- 28503539
TI  - Differences in Pes Planus and Pes Cavus subtalar eversion/inversion before and
      after prolonged running, using a two-dimensional digital analysis.
AB  - In sports, there is a constant discussion about the hyper-pronation and
      supination of the foot during loading and its relation to injuries or discomfort.
      The purpose of the present study was to investigate the possible differences in
      the subtalar joint in the midstance phase of running, between individuals with
      Pes Planus and Pes Cavus, after 5 min and 45 min of running. Thirty-four
      subjects, meeting the requirements for Pes Planus (30 feet) and Pes Cavus (35
      feet), according to the criteria for Medial Longitudinal Arch-angle, were
      included in the study. The calcaneal vertical angle, representing the
      eversion/inversion of the subtalar joint, was measured using with two-dimensional
      digital analysis and Dartfish Software with the subjects running barefoot on a
      treadmill, before and after 45 min of outside running wearing shoes. Both
      individuals with Pes Cavus and Pes Planus showed a significant increase in the
      calcaneal eversion (P<0.05) after 45 min of running. Between the groups, there
      was a significantly greater eversion of the Pes Planus, on the right foot, after
      45 min of running (P<0.05) compared to the Pes Cavus. The effect of fatigue
      evident in the present study suggests that further biomechanical research should
      be considered when exposing the foot to the repetitive nature of running,
      conditions most likely responsible for the overrepresented overuse injuries among
      runners.

PMID- 28503540
TI  - Comparisons of incidence of spinal and lower extremity deformities according to
      the physical characteristics between sports major and nonmajor college students.
AB  - This research was performed to identify the incidence of spinal and lower
      extremity deformity and to identify the relationship of the incidence between the
      physical characteristics. One hundred forty-seven Physical Education major
      students and 54 nonmajor students participated in this study. Data collecting was
      performed by questionnaire and visual postural evaluation. The incidences of genu
      varus (P<0.00001), genu recurvatum (P=0.0007), forward head (P<0.00001), lordosis
      (P<0.00001), and scoliosis (P=0.0008) were significantly lower in non-major
      students compared to major students. The incidences of genu varus (P=0.0017), leg
      length discrepancy (P=0.0015), and forward head (P=0.005) were significantly
      greater in women than their counterpart. However, in genu recurvatum (P<0.00001),
      kyphosis (P=0.0001), and lordosis (P=0.0024), the incidences were significantly
      lower in women. Overweight (body mass index [BMI]>24.5 kg/m2) students showed
      significantly high incidence (4.7 times, P=0.0044) in genu varus compared to
      students with normal BMI, and revealed significantly low incidence in genu
      recurvatum (P=0.0047) and protruding abdomen (P=0.0002).

PMID- 28503541
TI  - Effects of 12-week core stabilization exercise on the Cobb angle and lumbar
      muscle strength of adolescents with idiopathic scoliosis.
AB  - To identify the effects of core stabilization exercise on the Cobb angle and
      lumbar muscle strength of adolescent patients with idiopathic scoliosis. Subjects
      in the present study consisted of primary school students who were confirmed to
      have scoliosis on radiologic examination performed during their visit to the
      National Fitness Center in Seoul, Korea. Depending on whether they participated
      in a 12-week core stabilization exercise program, subjects were divided into the
      exercise (n=14, age 12.71+/-0.72 years) or control (n=15, age 12.80+/-0.86 years)
      group. The exercise group participated in three sessions of core stabilization
      exercise per week for 12 weeks. The Cobb angle, flexibility, and lumbar muscle
      strength tests were performed before and after core stabilization exercise.
      Repeated-measure two-way analysis of variance was performed to compare the
      treatment effects between the exercise and control groups. There was no
      significant difference in thoracic Cobb angle between the groups. The exercise
      group had a significant decrease in the lumbar Cobb angle after exercise compared
      to before exercise (P<0.001). The exercise group also had a significant increase
      in lumbar flexor and extensor muscles strength after exercise compared to before
      exercise (P<0.01 and P<0.001, respectively). Core stabilization exercise can be
      an effective therapeutic exercise to decrease the Cobb angle and improve lumbar
      muscle strength in adolescents with idiopathic scoliosis.

PMID- 28503542
TI  - Role of physical activity in mortality prediction in elderly hospice patients.
AB  - The prediction of life-expectancy in terminally ill patients is important both
      for medical and social reasons but it is widely recognized as being inaccurate.
      The aim of this study was to investigate the mortality predictors and indicators
      of life extension among elderly patients in a hospice service center. In order to
      determine the mortality predictors, we investigated the relationship between
      patients' cognitive status using the Korean-Mini Mental State Examination &
      Global Deterioration Scale (K-MMSE & GDS), the patient's physical function using
      the instrumental Activities of Daily Living (ADL) score, and the patient's blood
      component values. The subjects included 43 men and 57 women with a mean age of
      82.4+/-8.4 years, and a mean nursing period of 11.1+/-12.2 months. These
      terminally ill patients were enrolled in a cross-sectional study. All data were
      collected from paper and electronic charts, and patient interviews. A simple
      correlation analysis was performed to determine the relationship between the
      variables and to satisfy the normal distribution (P<0.01). The results revealed
      that the time of death negatively correlated with ADL score (r=-0.273, P=0.006).
      However, the K-MMSE & GDS, and the values of blood component such as albumin,
      gamma-glutamic transpeptidase, blood urea nitrogen, and creatinine were not
      correlated with the time of death. Consequently, the ADL score might be an
      important predictor of mortality and life extension in elderly patients.
      Therefore, in order to improve ADL score, physical exercise and overall fitness
      may be potential non-pharmacologic methods useful in preventing mortality in
      elderly people.

PMID- 28503543
TI  - IRAK4 Deficiency in a Patient with Recurrent Pneumococcal Infections: Case Report
      and Review of the Literature.
AB  - Primary immunodeficiencies are genetic defects of the innate or adaptive immune
      system, resulting in a propensity to infections. The innate immune system is the
      first line of defense against pathogens and is critical to recognize microbes and
      start the inflammatory cascade. Sensing of microbes occurs by a number of
      pathogen-recognition receptors, resulting in the activation of inflammatory
      signal transduction pathways, such as the activation of NF-kappaB. Herein, we
      describe a case of IRAK4 deficiency, a key signal transduction molecule of toll
      like and IL-1 receptors. We highlight the complexities in diagnosis of these
      disorders and review genetic defects of the NF-kappaB pathway.

PMID- 28503545
TI  - Relationship of Allergy with Asthma: There Are More Than the Allergy "Eggs" in
      the Asthma "Basket".
AB  - Asthma and allergy share a similar and very close course, especially through
      childhood. Considerable research effort has been put in untangling these
      associations; however, it is now becoming obvious that this is an exceedingly
      difficult task. In fact, each research breakthrough further perplexes this
      picture, as we are steadily moving toward the era of personalized medicine and we
      begin to appreciate that what we thought to be a single disease, asthma, is in
      fact an accumulation of distinct entities. In the context of this "syndrome,"
      which is characterized by several, as of yet poorly defined endotypes and
      phenotypes, the question of the link of "asthma" with allergy probably becomes
      non-relevant. In this review, we will revisit this question while putting the
      emphasis on the multifaceted nature of asthma.

PMID- 28503544
TI  - Update on Foregut Molecular Embryology and Role of Regenerative Medicine
      Therapies.
AB  - Esophageal atresia (OA) represents one of the commonest and most severe
      developmental disorders of the foregut, the most proximal segment of the
      gastrointestinal (GI) tract (esophagus and stomach) in embryological terms. Of
      intrigue is the common origin from this foregut of two very diverse functional
      entities, the digestive and respiratory systems. OA appears to result from
      incomplete separation of the ventral and dorsal parts of the foregut during
      development, resulting in disruption of esophageal anatomy and frequent
      association with tracheo-oesophageal fistula. Not surprisingly, and likely
      inherent to OA, are associated abnormalities in components of the enteric
      neuromusculature and ultimately loss of esophageal functional integrity. An
      appreciation of such developmental processes and associated defects has not only
      enhanced our understanding of the etiopathogenesis underlying such devastating
      defects but also highlighted the potential of novel corrective therapies. There
      has been considerable progress in the identification and propagation of neural
      crest stem cells from the GI tract itself or derived from pluripotent cells. Such
      cells have been successfully transplanted into models of enteric neuropathy
      confirming their ability to functionally integrate and replenish missing or
      defective enteric nerves. Combinatorial approaches in tissue engineering hold
      significant promise for the generation of organ-specific scaffolds such as the
      esophagus with current initiatives directed toward their cellularization to
      facilitate optimal function. This chapter outlines the most current understanding
      of the molecular embryology underlying foregut development and OA, and also
      explores the promise of regenerative medicine.

PMID- 28503547
TI  - Theoretically Guided Analytical Method Development and Validation for the
      Estimation of Rifampicin in a Mixture of Isoniazid and Pyrazinamide by UV
      Spectrophotometer.
AB  - A simple, rapid, economic, accurate, and precise method for the estimation of
      rifampicin in a mixture of isoniazid and pyrazinamide by UV spectrophotometeric
      technique (guided by the theoretical investigation of physicochemical properties)
      was developed and validated. Theoretical investigations revealed that isoniazid
      and pyrazinamide both were freely soluble in water and slightly soluble in ethyl
      acetate whereas rifampicin was practically insoluble in water but freely soluble
      in ethyl acetate. This indicates that ethyl acetate is an effective solvent for
      the extraction of rifampicin from a water mixture of isoniazid and pyrazinamide.
      Computational study indicated that pH range of 6.0-8.0 would favor the extraction
      of rifampicin. Rifampicin is separated from isoniazid and pyrazinamide at pH 7.4
      +/- 0.1 by extracting with ethyl acetate. The ethyl acetate was then analyzed at
      lambdamax of 344.0 nm. The developed method was validated for linearity, accuracy
      and precision according to ICH guidelines. The proposed method exhibited good
      linearity over the concentration range of 2.5-35.0 MUg/mL. The intraday and inter
      day precision in terms of % RSD ranged from 1.09 to 1.70% and 1.63 to 2.99%,
      respectively. The accuracy (in terms of recovery) of the method varied from of
      96.7 +/- 0.9 to 101.1 +/- 0.4%. The LOD and LOQ were found to be 0.83 and 2.52
      MUg/mL, respectively. In addition, the developed method was successfully applied
      to determine rifampicin combination (isoniazid and pyrazinamide) brands available
      in Bangladesh.

PMID- 28503546
TI  - Computational Tool for Fast in silico Evaluation of hERG K+ Channel Affinity.
AB  - The development of a novel comprehensive approach for the prediction of hERG
      activity is herein presented. Software Phase has been used to derive a 3D-QSAR
      model, employing as alignment rule a common pharmacophore built on a subset of 22
      highly active compounds (threshold Ki: 50 nM) against hERG K+ channel. Five
      features comprised the pharmacophore: two aromatic rings (R1 and R2), one
      hydrogen-bond acceptor (A), one hydrophobic site (H), and one positive ionizable
      function (P). The sequential 3D-QSAR model developed with a set of 421 compounds
      (randomly divided in training and test set) yielded a test set (Q2) = 0.802 and
      proved to be predictive with respect to an external test set of 309 compounds
      that were not used to generate the model ([Formula: see text] = 0.860).
      Furthermore, the model was submitted to an in silico validation for assessing the
      reliability of the approach, by applying a decoys set, evaluating the Guner and
      Henry score (GH) and the Enrichment Factor (EF), and by using the ROC curve
      analysis. The outcome demonstrated the high predictive power of the inclusive 3D
      QSAR model developed for the hERG K+ channel blockers, confirming the fundamental
      validity of the chosen approach for obtaining a fast proprietary cardiotoxicity
      predictive tool to be employed for rationally designing compounds with reduced
      hERG K+ channel activity at the early steps of the drug discovery trajectory.

PMID- 28503548
TI  - Exploiting Self-organization in Bioengineered Systems: A Computational Approach.
AB  - The productivity of bioengineered cell factories is limited by inefficiencies in
      nutrient delivery and waste and product removal. Current solution approaches
      explore changes in the physical configurations of the bioreactors. This work
      investigates the possibilities of exploiting self-organizing vascular networks to
      support producer cells within the factory. A computational model simulates de
      novo vascular development of endothelial-like cells and the resultant network
      functioning to deliver nutrients and extract product and waste from the cell
      culture. Microbial factories with vascular networks are evaluated for their
      scalability, robustness, and productivity compared to the cell factories without
      a vascular network. Initial studies demonstrate that at least an order of
      magnitude increase in production is possible, the system can be scaled up, and
      the self-organization of an efficient vascular network is robust. The work
      suggests that bioengineered multicellularity may offer efficiency improvements
      difficult to achieve with physical engineering approaches.

PMID- 28503551
TI  - A Case of Fibrillary Glomerulonephritis with Fibril Deposition in the Arteriolar
      Wall and a Family History of Renal Disease.
AB  - Herein, we report a case of fibrillary glomerulonephritis (FGN). FGN usually
      shows non-amyloidal fibrils in the mesangium and glomerular capillary walls on
      electron microscopy. Inherited cases of FGN have been reported in only 3
      families, and the suspected genetic form was autosomal dominant. In the present
      case, the deposition of microfibrils in the arteriolar wall as well as the
      glomerulus is unique. Our patient's father died of nephrotic syndrome, and his
      elder brother had a biopsy-proven glomerulopathy. The histological findings of
      the brothers are similar to mesangial proliferative glomerulonephritis and
      resemble each other. Therefore, our case is presumed to be familial FGN.
      Additionally, herein, we review the literature and reconsider the histological
      and clinical characters of FGN.

PMID- 28503549
TI  - Learning from Mother Nature: Innovative Tools to Boost Endogenous Repair of
      Critical or Difficult-to-Heal Large Tissue Defects.
AB  - For repair of chronic or difficult-to-heal tissue lesions and defects, major
      constraints exist to a broad application of cell therapy and tissue engineering
      approaches, i.e., transplantation of "ex vivo" expanded autologous
      stem/progenitor cells, alone or associated with carrier biomaterials. To enable a
      large number of patients to benefit, new strategies should be considered. One of
      the main goals of contemporary regenerative medicine is to develop new
      regenerative therapies, inspired from Mother Nature. In all injured tissues, when
      platelets are activated by tissue contact, their released factors promote innate
      immune cell migration to the wound site. Platelet-derived factors and factors
      secreted by migrating immune cells create an inflammatory microenvironment, in
      turn, causing the activation of angiogenesis and vasculogenesis processes.
      Eventually, repair or regeneration of the injured tissue occurs via paracrine
      signals activating, mobilizing or recruiting to the wound site cells with healing
      potential, such as stem cells, progenitors, or undifferentiated cells derived
      from the reprogramming of tissue differentiated cells. This review, largely based
      on our studies, discusses the identification of new tools, inspired by cellular
      and molecular mechanisms overseeing physiological tissue healing, that could
      reactivate dormant endogenous regeneration mechanisms lost during evolution and
      ontogenesis.

PMID- 28503550
TI  - Design of Surfactant Protein B Peptide Mimics Based on the Saposin Fold for
      Synthetic Lung Surfactants.
AB  - Surfactant protein (SP)-B is a 79-residue polypeptide crucial for the biophysical
      and physiological function of endogenous lung surfactant. SP-B is a member of the
      Saposin or Saposin-like proteins (SAPLIP) family of proteins that share an
      overall three-dimensional folding pattern based on secondary structures and
      disulfide connectivity and exhibit a wide diversity of biological functions. Here
      we review the synthesis, molecular biophysics and activity of synthetic analogs
      of Saposin proteins designed to mimic those interactions of the parent proteins
      with lipids that enhance interfacial activity. Saposin proteins generally
      interact with target lipids as either monomers or multimers via well-defined
      amphipathic helices, flexible hinge domains, and insertion sequences. Based on
      the known 3D-structural motif for the Saposin family, we show how bioengineering
      techniques may be used to develop minimal peptide constructs that maintain
      desirable structural properties and activities in biomedical applications. One
      important application is the molecular design, synthesis and activity of Saposin
      mimics based on the SP-B structure. Synthetic lung surfactants containing active
      SP-B analogs may be potentially useful in treating diseases of surfactant
      deficiency or dysfunction including the neonatal respiratory distress syndrome
      and acute lung injury/acute respiratory distress syndrome.

PMID- 28503552
TI  - Impact of Isolated Tricuspid Valve Repair on Right Ventricular Remodelling in an
      Adult Congenital Heart Disease Population.
AB  - BACKGROUND: Surgical repair of isolated congenital tricuspid valve (TV) disease
      is rare with no well-defined indication and outcomes. Moreover, the role of right
      ventricle (RV) in this context has not yet been investigated. OBJECTIVES: We
      sought to assess the impact of congenital TV repair on cardiac remodelling and
      clinical-functional status and the importance of the RV function in an adult
      congenital heart disease (ACHD) population. METHODS AND RESULTS: From January
      2005 to December 2015, 304 patients underwent TV surgery in our centre. Of these,
      27 (ACHD) patients had isolated TV repair. Patients were evaluated with
      preoperative and postoperative transthoracic echocardiogram. Survival rate has
      been investigated with a mean clinical follow-up (FU) of 3.7 +/- 2.3 years,
      whereas the mean echocardiographic FU was 2.9 +/- 1.8 years. The clinical and
      functional status of patients showed a statistically significant improvement
      after the surgical repair in terms of New York Heart Association class (66.7 vs
      7.4%; p < 0.01), clinical signs of heart failure (29.6 vs 7.4%; p < 0.01), and
      left ventricular function (14.8 vs 7.4%; p < 0.01). The RV and right atrium
      diameter were significantly reduced after surgery (5.15 +/- 1.21 vs 4.32 +/-
      1.16; p < 0.01) and (44.7 +/- 16.7 vs 26.7 +/- 9.2; p < 0.01), respectively. The
      degree of postoperative pulmonary hypertension was also significantly reduced
      (40.7 vs 7.4%; p < 0.01). The survival rate was 96.3% at 1 year and 93.7% at 5
      years. One patient (3.7%) had early failure of the tricuspid repair requiring a
      reoperation. CONCLUSION: Isolated TV repair for adult congenital disease
      significantly improved patients' clinical and functional status and allowed right
      ventricular remodelling and functional improvement.

PMID- 28503553
TI  - Elephant-Initiated Interactions with Humans: Individual Differences and Specific
      Preferences in Captive African Elephants (Loxodonta africana).
AB  - South Africa has seen a recent increase in the number of African elephants
      (Loxodonta africana) maintained in reserves and parks and managed in free
      contact, where they may spend a significant amount of time in close proximity to
      humans. This study investigates how individual elephants choose to initiate
      interactions with humans by examining whether interaction types and frequencies
      vary both between elephants and with regards to the category of human involved in
      the interaction. Observations were made on a herd of seven captive African
      elephants frequently exposed to elephant handlers (guides), volunteers (who carry
      out general observations for the park's research unit), and tourists. The
      elephants differed in the frequencies with which they initiated interactions with
      each category of human and in the types of behaviors they used to initiate
      interactions. However, all of the elephants interacted most frequently with
      guides. Certain individual elephants showed preferences in interacting with
      specific guides, indicating particular elephant-guide bonds. This study provides
      evidence for elephant-handler bonds as well as information on the extent of
      interactions between humans and African elephants managed in free contact.

PMID- 28503554
TI  - Multimodality imaging of intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinomas account for approximately 20% of cases of
      cholangiocarcinomas. Three growth patterns or morphologic subtypes exist,
      including mass-forming, periductal-infiltrating, and intraductal-growth subtypes.
      Knowledge of these morphologic subtypes and their radiologic appearance aids in
      timely diagnosis, a key to optimizing patient outcomes. The morphologic
      variability of intrahepatic cholangiocarcinomas has a direct impact on the
      diagnostic sensitivity and specificity of various diagnostic imaging modalities,
      including ultrasound (US), computed tomography (CT), magnetic resonance imaging
      (MRI)/magnetic resonance cholangiopancreatography (MRCP), and positron emission
      tomography (PET). The following review emphasizes optimal imaging technique for
      each of these modalities and reviews the imaging appearance of each morphologic
      subtype of intrahepatic cholangiocarcinoma.

PMID- 28503557
TI  - Epidemiology and risk factors: intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a rare entity with a distinct clinical
      course and epidemiology from hilar and extrahepatic cholangiocarcinoma. ICC makes
      up 8-10% of cholangiocarcinomas and 10-20% of all primary liver tumors. There
      remains a considerable amount of geographic variation in the incidence of ICC
      worldwide; however, the overall incidence of this malignancy appears to be
      rising. Several risk factors have been identified, such as infectious causes
      (liver flukes, viral hepatitis), biliary tract disease [primary sclerosing
      cholangitis (PSC), hepaticolithiasis, biliary cystic diseases], metabolic
      syndrome, lifestyle choices (alcohol abuse, tobacco use), and cirrhosis. Despite
      this, a substantial number of ICC patients do not have any identifiable risk
      factors, underlining the need for further work into the pathogenesis of this
      malignancy.

PMID- 28503556
TI  - Therapeutic options for intrahepatic cholangiocarcinoma.
AB  - Biliary tract cancer (BTC) is a heterogeneous group of cancers, which is composed
      of intrahepatic cholangiocarcinoma (ICCA), extrahepatic cholangiocarcinoma
      (ECCA), gallbladder cancers and ampullary carcinomas. While all anatomic
      subgroups are treated uniformly, our understanding about the pathogenesis has
      allowed us to reason that each group represents a clinically and genetically
      diverse disease. The majority of patients present with locally advanced or
      metastatic disease, where the standard treatment is combination systemic
      cytotoxic chemotherapy with gemcitabine and cisplatin. While most receive a
      clinical benefit from chemotherapy, patients eventually progress where no
      standardized therapies are available in the refractory setting. With the use of
      next generation sequencing, we have come to understand that ICCA is a diverse
      genomic disease with many actionable alterations that may serve as potential
      therapeutic targets. Further studies investigating the role of novel targeted
      agents (as a single agent or with combination chemotherapy) will hopefully
      provide additional treatment options for this highly lethal disease.

PMID- 28503555
TI  - Surgical options for intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver
      cancer, accounting for 10-15% of primary hepatic malignancy. The incidence and
      cancer-related mortality of ICC continue to increase worldwide. At present,
      hepatectomy is still the most effective treatment for ICC patients to achieve
      long-term survival, although its overall efficacy may not be as good as that for
      patients with hepatocellular carcinoma (HCC) due to the unique pathogenesis and
      clinical-pathological profiles of ICC. Viral infection, lithiasis and metabolic
      factors may all be associated with the pathogenesis of ICC. Poor blood supply,
      cirrhosis (in rare cases), surrounding organ invasion, and lymph node/distal
      metastasis have significant impacts on the selection of surgical strategies,
      surgical resection rate, postoperative complications, recurrence and metastasis.
      Surgical treatment for ICC includes R0 resection, lymphadenectomy, total gross
      resection of the involved biliary tracts, blood vessels and surrounding tissues
      in adjacent organs, and reconstruction. Postoperative adjuvant therapy and local
      regional therapy after recurrence may improve survival. Liver transplantation
      (LT) is reported to have a moderate treatment effect on early ICC although its
      efficacy remains controversial. In this article, we reviewed the epidemiology and
      staging of ICC and highlighted the selection of surgical modalities and
      postoperative outcomes of ICC patients via literature review.

PMID- 28503558
TI  - Management of unresectable intrahepatic cholangiocarcinoma: how do we decide
      among the various liver-directed treatments?
AB  - Intrahepatic cholangiocarcinoma often causes death due to obstruction of the
      biliary system or interruption of the vascular supply of the liver. This fact
      emphasizes the critical need for local tumor control in this disease. Successful
      local tumor control has traditionally been achievable through surgical resection
      for the small proportion of patients with operable tumors. Technological advances
      in radiation oncology and in interventional radiology have enabled the delivery
      of ablative radiation doses or other cytotoxic therapies for tumors in the liver.
      In some cases, this has translated into substantial prolongation of life for
      patients with this disease, but the indications for these different treatment
      options are still the subject of ongoing debate. Here, we review the
      technological advances and clinical studies that are changing the way
      intrahepatic cholangiocarcinoma is managed, and discuss ways to achieve
      individualized treatment of patients.

PMID- 28503560
TI  - Green tea and the question of reduced liver cancer risk: the dawn of potential
      clinical relevance?

PMID- 28503559
TI  - Cell-free DNA methylation as liquid biopsy for the assessment of fibrosis in
      patients with nonalcoholic steatohepatitis: a gap between innovation and
      implementation.

PMID- 28503561
TI  - Green tea and liver cancer.

PMID- 28503562
TI  - The natural history of nonalcoholic fatty liver disease: mortality rates and
      liver enzymes.

PMID- 28503563
TI  - Emerging new standard for non-invasive assessment of liver disease mortality in
      non-alcoholic fatty liver disease.

PMID- 28503564
TI  - Modelling western dietary habits in the mouse: easier said than done.

PMID- 28503565
TI  - Healthy gut microbiota can resolve undernutrition.

PMID- 28503566
TI  - Determination of the Use of Lactobacillus plantarum and Propionibacterium
      freudenreichii Application on Fermentation Profile and Chemical Composition of
      Corn Silage.
AB  - Corn was inoculated with Lactobacillus plantarum and Propionibacterium
      freudenreichii subsp. shermanii either independently or as a mixture at ensiling,
      in order to determine the effect of bacterial additives on corn silage quality.
      Grain corn was harvested at 32-37% of dry matter and ensiled in a 4 L laboratory
      silo. Forage was treated as follows: bacterial types: B0 (without bacteria
      control), B1 (L. plantarum), B2 (P. freudenreichii subsp. shermanii), and B3
      (combination of L. plantarum and P. freudenreichii subsp. shermanii). Each 2 kg
      of chopped forage was treated with 10 mL of bacterial culture and allowed to
      ferment for 27 days. The first experiment determined the most suitable wavelength
      for detection of bacteria (490 nm and 419 nm for B1 and B2, resp.) and the
      preferable inoculation size (1 * 105 cfu/g). The second experiment analysed the
      effect of B1 and B2 applied singly or as a mixture on the fermentation
      characteristics and quality of corn silage. L. plantarum alone increased crude
      protein (CP) and reduced pH rapidly. In a mixture with P. freudenreichii, the
      final pH was the lowest compared to other treatments. As a mixture, inclusion of
      bacteria resulted in silage with lower digestibility than control. Corn silage
      treated with L. plantarum or P. freudenreichii either alone or mixed together
      produced desirable silage properties; however, this was not significantly better
      than untreated silage.

PMID- 28503568
TI  - A Novel -72 (T->A) beta-Promoter Mutation Causing Slightly Elevated HbA2 in a
      Vietnamese Heterozygote.
AB  - We report a novel beta+-thalassemia mutation found in a Vietnamese family. The
      molecular defect T->A lies at -72 of the beta-globin gene promoter, within the
      conserved CCAAT box. The index case was a 5-year-old child having red blood cells
      indices close to normal and slightly increased level of HbA2 (3.96%). The
      expression of the mutated beta allele was inferred by luciferase reporter assay
      in K562 cells. The beta -72 determinant is the eighth beta-thalassemic mutation
      identified in Vietnam and it was not previously reported in any population. The
      absence of homozygous or compound heterozygous states did not allow us to
      precisely predict either its clinical impact or its relevance in management
      programs. Our results further underline the importance of identifying and
      characterizing new or rare beta+-thalassemic alleles in carrier screening and
      prenatal diagnosis.

PMID- 28503567
TI  - Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential
      Therapeutic Role of Exercise.
AB  - Chronic kidney disease (CKD) is considered a model of accelerated aging. More
      specifically, CKD leads to reduced physical functioning and increased frailty,
      increased vascular dysfunction, vascular calcification and arterial stiffness,
      high levels of systemic inflammation, and oxidative stress, as well as increased
      cognitive impairment. Increasing evidence suggests that the cognitive impairment
      associated with CKD may be related to cerebral small vessel disease and overall
      impairment in white matter integrity. The triad of poor physical function,
      vascular dysfunction, and cognitive impairment places patients living with CKD at
      an increased risk for loss of independence, poor health-related quality of life,
      morbidity, and mortality. The purpose of this review is to discuss the available
      evidence of cerebrovascular-renal axis and its interconnection with early and
      accelerated cognitive impairment in patients with CKD and the plausible role of
      exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis
      pathophysiological link and its interconnection with physical function is
      important for clinicians in order to minimize the risk of loss of independence
      and improve quality of life in patients with CKD.

PMID- 28503569
TI  - Postneonatal Mortality and Liver Changes in Cloned Pigs Associated with Human
      Tumor Necrosis Factor Receptor I-Fc and Human Heme Oxygenase-1 Overexpression.
AB  - Soluble human tumor necrosis factor (shTNFRI-Fc) and human heme oxygenase 1 (hHO
      1) are key regulators for protection against oxidative and inflammatory injury
      for xenotransplantation. Somatic cells with more than 10 copy numbers of shTNFRI
      Fc and hHO-1 were employed in somatic cell nuclear transfer to generate cloned
      pigs, thereby resulting in seven cloned piglets. However, produced piglets were
      all dead within 24 hours after birth. Obviously, postnatal death with liver
      apoptosis was reported in the higher copy number of shTNFRI-Fc and hHO-1 piglets.
      In liver, the transcript levels of ferritin heavy chain, light chain,
      transferrin, and inducible nitric oxide synthase were significantly highly
      expressed compared to those of lower copy number of shTNFRI-Fc and hHO-1 piglets
      (P < 0.05). Also, H2O2 contents were increased, and superoxide dismutase was
      significantly lower in the higher copy number of shTNFRI-Fc and hHO-1 piglets (P
      < 0.05). These results indicate that TNFRI-Fc and hHO-1 overexpression may
      apparently induce free iron in the liver and exert oxidative stress by enhancing
      reactive oxygen species production and block normal postneonatal liver
      metabolism.

PMID- 28503570
TI  - A Frailty Index from Next-of-Kin Data: A Cross-Sectional Analysis from the
      Mexican Health and Aging Study.
AB  - Objectives. To construct a frailty index from next-of-kin information of the last
      year of life of community-dwelling 50 years old or older adults and test its
      association with health services utilization. Methods. Cross-sectional analysis
      from next-of-kin data available from the last wave of the Mexican Health and
      Aging Study (MHAS). Measurements. Along with descriptive statistics, the frailty
      index (FI) was tested in regression models to assess its association with adverse
      outcomes previous to death: number of hospitalized days in the previous year and
      number of visits to a physician in the previous year, in unadjusted and adjusted
      models. Results. From a total of 2,649 individuals the mean of age was 74.8 (+/
      11.4) and 56.3% (n = 1,183) were women. The mean of the FI was of 0.279 (+/-SD
      0.131, R = 0.0-0.738) and distribution was biased to the right. There was a
      significant association (p < 0.001) between the FI and number of hospitalized
      days (beta = 45.7, 95% CI 36.1-55.4, p < 0.001) and for the number of visits to a
      physician (beta = 25.93, 95% CI 19.27-32.6, p < 0.001) both models adjusted for
      age and sex. Conclusion. The FI constructed with next-of-kin data showed similar
      characteristics to similar indexes of older adults. It was independently
      associated with health care use.

PMID- 28503572
TI  - Learning Curve and Clinical Outcomes of Performing Surgery with the InterTan
      Intramedullary Nail in Treating Femoral Intertrochanteric Fractures.
AB  - Purpose. The purpose of this study is to evaluate the learning curve of
      performing surgery with the InterTan intramedullary nail in treating femoral
      intertrochanteric fractures, to provide valuable information and experience for
      surgeons who decide to learn a new procedure. Methods. We retrospectively
      analyzed data from 53 patients who underwent surgery using an InterTan
      intramedullary nail at our hospital between July 2012 and September 2015. The
      negative exponential curve-fit regression analysis was used to evaluate the
      learning curve. According to 90% learning milestone, patients were divided into
      two group, and the outcomes were compared. Results. The mean operative time was
      69.28 (95% CI 64.57 to 74.00) minutes; with the accumulation of surgical
      experience, the operation time was gradually decreased. 90% of the potential
      improvement was expected after 18 cases. In terms of operative time,
      intraoperative blood loss, hospital stay, and Harris hip score significant
      differences were found between two groups (p = 0.009, p = 0.000, p = 0.030, and p
      = 0.002, resp.). Partial weight bearing time, fracture union time, tip apex
      distance, and the number of blood transfusions and complications were similar
      between two groups (p > 0.5). Conclusion. This study demonstrated that the
      learning curve of performing surgery with the InterTan intramedullary nail is
      acceptable and 90% of the expert's proficiency level is achieved at around 18
      cases.

PMID- 28503571
TI  - Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression.
AB  - Background. Depression is a recurrent, common, and potentially life-threatening
      psychiatric disease related to multiple assignable causes. Although conventional
      antidepressant therapy can help relieve symptoms of depression and prevent
      relapse of the illness, complementary therapies are required due to disadvantage
      of the current therapy such as adverse effects. Moreover, a number of studies
      have researched adjunctive therapeutic approaches to improve outcomes for
      depression patients. Purpose. One potential complementary method with
      conventional antidepressants involves the use of medicinal herbs and
      phytochemicals that provide therapeutic benefits. Studies have revealed
      beneficial effects of medical herbs and phytochemicals on depression and their
      central nervous system mechanism. Here, we summarize the current knowledge of the
      therapeutic benefits of phytochemicals and medicinal herbs against depression and
      describe their detailed mechanisms. Sections. There are two sections,
      phytochemicals against depression and medical herbs against depression, in this
      review. Conclusion. Use of phytomedicine may be an alternative option for the
      treatment of depression in case conventional drugs are not applicable due to
      their side effects, low effectiveness, or inaccessibility. However, the efficacy
      and safety of these phytomedicine treatments for depression have to be supported
      by clinical studies.

PMID- 28503573
TI  - Collagen External Scaffolds Mitigate Intimal Hyperplasia and Improve Remodeling
      of Vein Grafts in a Rabbit Arteriovenous Graft Model.
AB  - Objectives. The aim of this study was to test the effects of collagen external
      scaffold (CES) in intimal hyperplasia of vein grafts and explore its underlying
      mechanisms. Methods. Thirty-six New Zealand white rabbits were randomized into no
      graft group, graft group, and CES group. The rabbit arteriovenous graft model was
      established. In CES group, the vein graft was wrapped around with CES. The
      hemodynamic parameters of vein grafts were measured intraoperatively and 4 weeks
      after operation by ultrasonic examination. Histological characteristics of vein
      grafts were also evaluated 4 weeks later. The mRNA and protein levels of
      proliferating cell nuclear antigen (PCNA), active cleaved-caspase-3 (ClvCasp-3),
      and smooth muscle 22 alpha (SM22alpha) were measured 4 weeks later by
      quantitative real-time PCR and western blot. Results. CES significantly improved
      the hemodynamic stability of vein grafts, with higher blood velocity and blood
      flow. Similarly, CES also markedly mitigated intimal hyperplasia and inhibited
      dilatation of vein grafts. In CES group, the upexpression of PCNA and ClvCasp-3
      and the downexpression of SM22alpha were inhibited. Conclusion. CES exerts
      beneficial effects in mitigating intimal hyperplasia and improving remodeling of
      autogenous vein grafts, which may be associated with reducing the proliferation
      and apoptosis and preserving the phenotype of VSMCs.

PMID- 28503574
TI  - Vitamin D Modulates Hematological Parameters and Cell Migration into Peritoneal
      and Pulmonary Cavities in Alloxan-Diabetic Mice.
AB  - Background/Aims. The effects of cholecalciferol supplementation on the course of
      diabetes in humans and animals need to be better understood. Therefore, this
      study investigated the effect of short-term cholecalciferol supplementation on
      biochemical and hematological parameters in mice. Methods. Male diabetic
      (alloxan, 60 mg/kg i.v., 10 days) and nondiabetic mice were supplemented with
      cholecalciferol for seven days. The following parameters were determined: serum
      levels of 25-hydroxyvitamin D, phosphorus, calcium, urea, creatinine, alanine
      aminotransferase, aspartate aminotransferase, alkaline phosphatase, red blood
      cell count, white blood cell count (WBC), hematocrit, hemoglobin, differential
      cell counts of peritoneal lavage (PeL), and bronchoalveolar lavage (BAL) fluids
      and morphological analysis of lung, kidney, and liver tissues. Results. Relative
      to controls, cholecalciferol supplementation increased serum levels of 25
      hydroxyvitamin D, calcium, hemoglobin, hematocrit, and red blood cell counts and
      decreased leukocyte cell counts of PeL and BAL fluids in diabetic mice. Diabetic
      mice that were not treated with cholecalciferol had lower serum calcium and
      albumin levels and hemoglobin, WBC, and mononuclear blood cell counts and higher
      serum creatinine and urea levels than controls. Conclusion. Our results suggest
      that cholecalciferol supplementation improves the hematological parameters and
      reduces leukocyte migration into the PeL and BAL lavage of diabetic mice.

PMID- 28503575
TI  - Association between NLPR1, NLPR3, and P2X7R Gene Polymorphisms with Partial
      Seizures.
AB  - Objectives. Clinical and experimental evidence has clarified that the
      inflammatory processes within the brain play a pivotal role in the
      pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic
      receptor (P2X7R) are important mediators during the inflammatory process.
      Therefore, we investigated the possible association between partial seizures and
      inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study.
      Method. A total of 163 patients and 201 health controls were enrolled in this
      study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using
      polymerase chain reaction- (PCR-) ligase detection reaction method. Result. The
      frequency of rs878329 (G>C) genotype with C (CG + CC) was significantly lower
      among patients with partial seizures relative to controls (OR = 2.033, 95% CI =
      1.290-3.204, p = 0.002 for GC + CC versus GG). Intriguingly, we found that the
      significant difference of rs878329 (G>C) genotype and allele frequency only
      existed among males (OR = 2.542, 95% CI = 1.344-4.810, p = 0.004 for GC + CC
      versus GG), while there was no statistically significant difference among
      females. However, no significant results were presented for the genotype
      distributions of rs8079034, rs4612666, rs10754558, rs2027432, rs3751143, and
      rs208294 polymorphisms between patients and controls. Conclusion. Our study
      demonstrated the potentially significant role of NLRP1 rs878329 (G>C) in
      developing susceptibility to the partial seizures in a Chinese Han population.

PMID- 28503576
TI  - Sirtuin 2 Regulates Microvascular Inflammation during Sepsis.
AB  - Objective. Sepsis and septic shock, the leading causes of death in noncoronary
      intensive care units, kill more than 200,000/year in the US alone. Circulating
      cell-endothelial cell interactions are the rate determining factor in sepsis
      inflammation. Sirtuin, a seven-member family of proteins (SIRT1-7),
      epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3,
      and 6 in sepsis previously. In this project, we studied the role of SIRT2 on
      sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT), SIRT2
      knockout (SIRT2KO), and SIRT2 overexpressing (SIRT2KI) mice by cecal ligation and
      puncture (CLP). We studied leukocyte/platelet adhesion using intravital
      microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small
      intestine with immunohistochemistry (IHC) six hours post-CLP/sham surgery. We
      also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice.
      Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice
      show attenuation of cellular adhesion with sepsis in the small intestine. We also
      show that the small intestinal E-selectin and ICAM-1 expressions increased in
      SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show
      that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI
      sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and
      affects survival.

PMID- 28503578
TI  - Brave New World.

PMID- 28503577
TI  - The Role of Proteinase-Activated Receptors 1 and 2 in the Regulation of
      Periodontal Tissue Metabolism and Disease.
AB  - Proteinase-activated receptors 1 (PAR1) and 2 (PAR2) are the most highly
      expressed members of the PAR family in the periodontium. These receptors regulate
      periodontal inflammatory and repair processes through their activation by
      endogenous and bacterial enzymes. PAR1 is expressed by the periodontal cells such
      as human gingival fibroblasts, gingival epithelial cells, periodontal ligament
      cells, osteoblasts, and monocytic cells and can be activated by thrombin, matrix
      metalloproteinase 1 (MMP-1), MMP-13, fibrin, and gingipains from Porphyromonas
      gingivalis. PAR2 is expressed by neutrophils, osteoblasts, oral epithelial cells,
      and human gingival fibroblasts, and its possible activators in the periodontium
      are gingipains, neutrophil proteinase 3, and mast cell tryptase. The mechanisms
      through which PARs can respond to periodontal enzymes and result in appropriate
      immune responses have until recently been poorly understood. This review
      discusses recent findings that are beginning to identify a cardinal role for PAR1
      and PAR2 on periodontal tissue metabolism.

PMID- 28503579
TI  - Anterior Commissure Involvement in Humanherpes Virus 6 Encephalitis.
AB  - The anterior commissure is an evolutionarily conserved nerve bundle that connects
      the right and left hemispheres, playing pivotal neurological roles in visual,
      linguistic, and olfactory functions. The authors herein describe a 16-month-old
      boy with high fever, lethargy, and recurrent seizures. Polymerase chain reaction
      (PCR) examination detected human herpesvirus 6 (HHV-6) in both the cerebrospinal
      fluid and the pharyngeal swabs, leading to the diagnosis of HHV-6 encephalitis.
      Brain magnetic resonance imaging (MRI) 4 days after disease onset distinctly
      revealed anterior commissure involvement on diffusion-weighted images and
      apparent diffusion coefficient maps, suggesting that this lesion was cytotoxic
      edema. After treatment with 30 mg/kg/d methylprednisolone for 3 days, the
      anterior commissure involvement on MRI was completely diminished. This is the
      first MRI report rarely showing anterior commissure involvement in encephalitis,
      suggesting that this lesion might be caused by direct invasion of HHV-6 or
      transient axonal swelling associated with inferior temporal lobe damage.

PMID- 28503581
TI  - A Case Report of Homocystinuria With Dystonia and Stroke.
AB  - Inherited homocystinuria is a rare autosomal recessive aminoacidopathy which
      through early diagnosis can prevent its severe neurologic and vascular
      complications. Here we report a 9-year-old girl with homocystinuria, presenting
      with sequential symptoms of bilateral lens dislocation, skeletal complication,
      and eventually dystonia from the age of 4 years. Laboratory evaluation revealed
      severe high serum homocysteine level. Although pathophysiologically unexplained,
      evidence of deep white matter watershed infarct along with remarkable ipsilateral
      carotid stenosis was detected on the contralateral side of the dystonia in the
      neuroimaging. Treatment with high dose of pyridoxine relieved limb and gait
      dystonia significantly, while carotid stenosis remained unchanged. Therefore,
      homocysteine might have both structural and irreversible effect and functional
      and reversible impact that could be overcome even in late stages.

PMID- 28503580
TI  - Connexin 43 and Its Hemichannels Mediate Hypoxia-Ischemia-Induced Cell Death in
      Neonatal Rats.
AB  - Wistar rat pups had the left common carotid artery cut, and they were exposed to
      8% oxygen with free access to food and water until they were killed at 1, 12, 24,
      and 48 hours after the hypoxia-ischemia (HI) insult. Connexin 43 (Cx43),
      hemichannel (HC1), and caspase 3 (Casp3) in cerebral HI tissues were examined by
      immunohistochemistry and Western blot analyses. Astrocytes cell line, astrocytes
      transduced with a retroviral empty vector (Psup astrocyte), or a Cx43-specific
      small hairpin RNA (shRNA) construct (shRNA astrocytes) was treated with oxygen
      glucose deprivation (OGD) insult. The viability of astrocytes was assessed by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results
      showed the expression of Cx43, HC1, and Casp3 in rats' brain, and astrocytes and
      Psup astrocytes increased significantly after 24 hours of HI/OGD insult. Cell
      viability decreased after 24 hours of the insult. The results suggest that Cx43
      and hemichannel are likely to mediate the astrocytic death after HI insult.

PMID- 28503582
TI  - Neuro-Behcets in a Child.
AB  - We describe a case of neuro-Behcet disease diagnosed in a 12-year-old girl. This
      patient presented with recurrent oral ulcers, incontinence, spastic gait, blurry
      vision, and asymmetrical lower extremity hypertonia. Extensive testing revealed
      punctate lesions through the central nervous system, vitritis, papillitis, and
      uveitis. A thorough infectious and neoplastic workup was negative. She was
      treated with pulse steroids and azathioprine with gradual improvement in her gait
      and ophthalmologic findings. Although rare, primary neuro-Behcet should be
      considered in pediatric patients with neurologic abnormalities and recurrent
      aphthous ulcers without other explanation.

PMID- 28503583
TI  - Childhood-Onset Progressive Dystonia With Mitochondrial DNA G14459A Mutation:
      Efficacy of Long-Term Sodium Succinate Treatment.
AB  - This article reports the case of an 11-year-old boy with progressive dystonia
      caused by the homoplasmic G14459A mitochondrial DNA mutation. The patient
      presented with focal dystonia in the right upper limb at 3 years of age, which
      progressed over 4 years to exhibit dystonia in both the upper and lower limbs. At
      7 years of age, high signal intensity lesions in the bilateral striata and the
      midbrain were observed on fluid-attenuated inversion recovery images. It was
      observed on diffusion-weighted images that with time, these high signal intensity
      lesions migrated from the putamen to the caudate nuclei, which closely correlated
      with disease progression. Because his symptoms and abnormal magnetic resonance
      imaging findings progressed despite treatment with coenzyme Q10 and l-carnitine,
      at 7 years of age he was then started on sodium succinate, hoping to improve his
      complex I deficiency. After treatment, progression of MRI abnormalities appeared
      to have been suppressed for 4 years, although no improvement was observed in
      dystonia.

PMID- 28503584
TI  - Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related
      Epilepsy Syndrome: A Case Series.
AB  - Febrile illness-related epilepsy syndrome is a catastrophic epileptic
      encephalopathy that is highly refractory to most antiepileptic drugs leading to
      high morbidity and mortality. The authors report the use of a pediatric infusion
      protocol of continuous intravenous magnesium sulfate for the control of seizures
      in 2 children with febrile illness-related epilepsy syndrome refractory to
      multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary
      care children's hospital. Both patients, 2 and 16 years of age, respectively,
      were treated with continuous magnesium sulfate infusion. Serum magnesium
      concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and
      cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No
      significant adverse effects were observed. Magnesium sulfate infusions can be
      safely used in pediatric refractory status epilepticus. Magnesium sulfate can be
      considered in the management of children with febrile illness-related epilepsy
      syndrome.

PMID- 28503585
TI  - Encephalocraniocutaneous Lipomatosis: A Rare Association With Tethered Spinal
      Cord Syndrome With Review of Literature.
AB  - Encephalocraniocutaneous lipomatosis or Haberland syndrome is a rare, congenital
      neurocutaneous syndrome. It is characterized by unilateral lipomatous hamartomata
      of the scalp, eyelid, and outer globe of the eye and ipsilateral neurologic
      malformations. We describe the first case from Lebanon, an infant with classical
      encephalocraniocutaneous lipomatosis characterized by nevus psiloliparus,
      unilateral right facial and frontal-temporal subcutaneous lipomas, alopecia,
      ocular coloboma, aniridia and eyelid nodular tags, ventriculomegaly with
      intracranial and intraspinal lipomas, and tethered spinal cord. We report this
      case of rare association between encephalocraniocutaneous lipomatosis and
      tethered spinal cord syndrome and stress on the importance of spinal cord
      evaluation in encephalocraniocutaneous lipomatosis.

PMID- 28503586
TI  - Spontaneous Malignant Transformation of a Pilocytic Astrocytoma of Cerebellum:
      Case Report.
AB  - Pilocytic astrocytoma is a slowly growing neoplasia that represents the most
      frequent cerebral tumor in pediatric age. Malignant transformation is rare and it
      is usually related to previous radiotherapy. The authors describe a case of a
      spontaneous malignant transformation of a pilocytic astrocytoma. A 3-year-old boy
      was diagnosed with a cerebellar hemisphere tumor. He was submitted to a complete
      excision of the lesion, and histological findings were consistent with pilocytic
      astrocytoma. It was negative for p53. Twelve years later he presented with a
      local recurrence. Histopathological diagnosis was glioblastoma and it was
      positive for p53. Death from disease progression occurred 16 months after the
      diagnosis of glioblastoma. This case suggests that patients with pilocytic
      astrocytoma need closer follow-up and further genotypic studies in order to
      provide clues to clinical behavior. Such understanding can allow us to stratify
      treatment accordingly and to proceed to more aggressive treatment when necessary.

PMID- 28503587
TI  - Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of
      Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors: A Case Report and
      Review of the Literature.
AB  - Diffuse leptomeningeal glioneuronal tumor is unique for communicating
      hydrocephalus, diffuse leptomeningeal enhancement, cystic changes, absence of
      tumor cells in cerebral spinal fluid, and a cell population of both glial and
      neuronal copositivity. It has likely been misdiagnosed as mixed glioneuronal
      tumors, oligodendrogliomas, and neuroepithelial tumors. Children with signs of
      this tumor are often worked up for infection, rheumatologic disease, or
      disseminated primary malignancy, resulting in unnecessary testing and treatment.
      We describe a 14-year-old female with recurrent headaches, hydrocephalus, and
      diffuse leptomeningeal enhancement discovered to be neoplastic 1 year after
      initial presentation, owing to extensive and unrevealing infectious and
      immunologic workups. Biopsies revealed atypical cells with markers of both glial
      and neuronal cells, positivity for OLIG-2, and focal p53 positivity. Great
      response was seen with temozolomide and craniospinal irradiation. Additionally,
      we postulate additional diagnostic indicators that may aid in earlier diagnosis
      and treatment decisions.

PMID- 28503588
TI  - Arthrogryposis Multiplex Congenita Related to Third-Trimester Basal Ganglia
      Ischemia: A Case Report.
AB  - Arthrogryposis multiplex congenita is a syndromic condition defined by
      contracture of 2 or more joints. A large range of etiologies has been reported
      such as neuromuscular disorders (peripheral dysfunction), chromosomal
      abnormalities, or cerebral malformations (central dysfunction) leading to fetal
      immobility. Severity of arthrogryposis depends on the etiology and duration of
      fetal immobility. The authors report a 34 gestational weeks infant presenting
      with severe diffuse arthrogryposis symptoms and respiratory failure at birth. Her
      mother experienced cardiac arrest at 29 gestational weeks due to carbon monoxide
      intoxication. Fetal magnetic resonance imaging revealed extensive corticospinal
      tract lesions. Antenatal ischemia of the deep gray matter needs to be considered
      as a possible arthrogryposis cause.

PMID- 28503589
TI  - FOXG1 Mutation is a Low-Incidence Genetic Cause in Atypical Rett Syndrome.
AB  - Due to the genetic and clinical heterogeneity of Rett syndrome, patients with
      nonclassic phenotypes are classified as an atypical Rett syndrome, that is,
      preserved speech variant, early seizure variant, and congenital variant.
      Respectively, MECP2, CDKL5, and FOXG1 have been found to be the causative genes,
      but FOXG1 variants are the rarest and least studied. We performed mutational
      analyses for FOXG1 on 11 unrelated patients without MECP2 and CDKL5 mutations,
      who were diagnosed with atypical Rett syndrome. One patient, who suffered from
      severe early-onset mental retardation and multiple-type intractable seizures,
      carried a novel, de novo FOXG1 mutation (p.Gln70Pro). This case concurs with
      previous studies that have reported yields of ~10%. FOXG1-related atypical Rett
      syndrome is rare in Korean population, but screening of this gene in patients
      with severe mental retardation, microcephaly, and early-onset multiple seizure
      types without specific genetic causes can help broaden the phenotypic spectrum of
      the distinct FOXG1-related syndrome.

PMID- 28503590
TI  - Clinical Phenotype of De Novo GNAO1 Mutation: Case Report and Review of
      Literature.
AB  - Mutations in the guanine nucleotide-binding protein (G protein), alpha activating
      activity polypeptide O (GNAO1) gene have recently been described in 6 patients
      with early infantile epileptic encephalopathies. In the present study, we report
      the phenotype and the clinical course of a 4-year-old female with an epileptic
      encephalopathy (Ohtahara syndrome) and profound intellectual disability due to a
      de novo GNAO1 mutation (c.692A>G; p.Tyr231Cys). Ohtahara syndrome is a
      devastating early infantile epileptic encephalopathy that can be caused by
      mutations in different genes, now also including GNAO1. The mutation was found
      using a targeted next generation sequencing gene panel and demonstrates targeted
      sequencing as a powerful tool for identifying mutations in genes where only a few
      de novo mutations have been identified.

PMID- 28503591
TI  - Prevalence and Characteristics of Chinese Patients With Duchenne and Becker
      Muscular Dystrophy: A Territory Wide Collaborative Study in Hong Kong.
AB  - The aim of this collaborative study on Duchenne muscular dystrophy and Becker
      muscular dystrophy is to determine the prevalence and to develop data on such
      patients as a prelude to the development of registry in Hong Kong. Information on
      clinical and molecular findings, and patient care, was systematically collected
      in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients
      with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy.
      The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10
      000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher
      percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon
      deletions in our patients when compared with overseas studies. Although we
      observed similar percentage of Duchenne group received scoliosis surgery,
      ventilation support, and cardiac treatment when compared with other countries,
      the percentage (25%) of steroid use is lower.

PMID- 28503592
TI  - Ictal 99mTc-Ethyl Cysteinate Dimer SPECT Findings of a Girl With Refractory
      Localization-Related Epilepsy Who Developed Transient Ictal Bradycardia.
AB  - Ictal bradycardia, which is considered to be one of the causes of sudden
      unexplained death in epilepsy, is rare. A 10-year-old girl with focal cortical
      dysplasia in her right centroparietal region developed transient ictal
      bradycardia during cluster seizures. Brain magnetic resonance imaging
      demonstrated a high signal intensity lesion adjacent to the focal cortical
      dysplasia lesion. Ictal 99mTc-ethyl cysteinate dimer single-photon emission
      computed tomography (SPECT) detected hyperperfusion in an area containing the
      high signal intensity lesion, which was located close to the insular cortex.
      Since the hyperperfusion zone observed on SPECT was considered to reflect seizure
      propagation, it is possible that the ictal bradycardia experienced in the present
      case was caused by the following mechanism: The repetitive seizure activity
      caused the high-intensity lesion seen on MRI to expand into the right insular
      cortex, which controls cardiac rhythm, resulting in ictal bradycardia.

PMID- 28503593
TI  - Transient Cerebral Arteriopathy in a Child Associated With Cytomegalovirus
      Infection.
AB  - Vascular wall injuries account for up to 80% of childhood strokes, excluding
      emboli of cardiac origin. Transient cerebral arteriopathy is a recently described
      entity that is increasingly recognized as an important cause. The cerebral
      arterial wall is thought to be affected by an inflammatory process related to
      certain infections. The authors report a 2.5-year-old girl with sudden left
      hemiplegia and aphasia. The neuroimaging showed occlusion of the right middle
      cerebral artery and ischemic damages. Laboratory revealed positive
      cytomegalovirus immunoglobulin M and G in cerebrospinal fluid and in early and
      late sera. Treatment with ganciclovir, anticytomegalovirus immunoglobulin, and
      prednisolone, followed by oral aspirin, resulted in clinical improvement. The
      follow-up neuroimaging showed stabilization of the arterial lesions without
      residual stenosis. To our knowledge, this is the first report of a
      cytomegalovirus-associated transient cerebral arteriopathy in an immunocompetent
      child. Our report demonstrates the propensity for cytomegalovirus to be involved
      in pediatric cerebral vascular disease.

PMID- 28503594
TI  - First Application of Ketogenic Diet on a Child With Intractable Epilepsy in
      Ghana.
AB  - The prevalence of epilepsy in sub-Saharan Africa is higher than in other parts of
      the world, but it is short of the effective measure on treating intractable
      epilepsy. Epilepsy surgery is not easy to be performed due to the high cost and
      demand of operational skills. The authors planned to perform ketogenic diet
      therapy for the children with intractable epilepsy in Ghana with regard to its
      low cost and simple procedure. The candidate is a 10-month-old girl with epilepsy
      with unknown etiology. Her seizures couldn't be controlled by more than 3
      antiepileptic drugs. Her development delayed severely due to frequent seizures.
      The authors successfully applied ketogenic diet for her. Her seizures were
      completely controlled after 2 weeks' therapy. Her mental condition was improved
      after that. The authors get much experience from this case for further developing
      ketogenic diet in Africa. This is the first report that ketogenic diet was
      applied to control intractable epilepsy in West Africa.

PMID- 28503596
TI  - Guillain Barre Syndrome in a Child With X-Linked Adrenoleukodystrophy.
AB  - X-Linked adrenoleukodystrophy is the most common peroxisomal disorder with
      different phenotypes among patients carrying the same ABCD1 mutation. There were
      previously reported associations of X-linked adrenoleukodystrophy with autoimmune
      disorders. The authors describe Guillain Barre syndrome in a child with X-linked
      adrenoleukodystrophy. The available evidence does not permit conclusion
      concerning etiological linkage between the 2 diseases, but it warrants further
      study.

PMID- 28503595
TI  - A New Observation of an Atypical and Severe Variant of the Guillain-Barre
      Syndrome in a Child: Remaining Challenges for Diagnosis, Nosologic
      Classification, and Therapeutic Course.
AB  - Guillain-Barre syndrome is a rare acute polyradiculoneuropathy. Several variants
      and unusual presentations have been described, particularly in pediatrics. In
      most cases, making an early diagnosis is challenging due to the treatments that
      consist in the rapid administration of intravenous immunoglobulin or plasma
      exchange. The authors present the case of a 7-year-old boy with an atypical and
      severe axonal Guillain-Barre syndrome, associated with Mycoplasma pneumonia. When
      he was admitted, febrile respiratory failure was the main focus, and then he
      presented signs of acute polyneuropathy with cranial nerve palsy and brief
      hyperreflexia. Mechanical ventilation was required for 48 days as well as 2
      cycles of intravenous immunoglobulin. The authors describe all the medical
      challenges that the authors encountered. This case highlights the fact that
      respiratory distress can be the main clinical symptom in children. This delays
      the establishment of a correct diagnosis, even more so when neurological
      manifestations are abundant and unusual.

PMID- 28503597
TI  - Vagal Nerve Stimulation in the Treatment of Drug-Resistant Epileptic
      Encephalopathies in Inborn Errors of Metabolism: Report of 2 Cases.
AB  - Patients affected by inborn errors of metabolism can develop catastrophic
      epilepsies ineligible for resective surgery. Few reports concerning vagal nerve
      stimulation in patients with epileptic encephalopathy in the context of metabolic
      diseases have been published in the literature. Drug-resistant epilepsies in
      metabolic disease could be a specific target for vagal nerve stimulation,
      although the efficacy of this technique in these patients still needs to be
      proved. The authors report our experience in treating refractory epilepsy with
      vagal nerve stimulation in 2 patients affected by inborn errors of metabolism.
      The first patient is a 23-year-old patient affected by glutaric aciduria type II,
      the other one is a 16-month-old child with nonketotic hyperglycinemia. Vagal
      nerve stimulation reduced seizures up to 50% in the first case and up to 90% in
      the second one.

PMID- 28503598
TI  - Assessing Children With Disabilities Using WHO International Classification of
      Functioning, Disability and Health Child and Youth Version Activities and
      Participation D Codes.
AB  - AIM: Evaluation of the International Classification of Functioning, Disability
      and Health child and youth version (ICF-CY) activities and participation d code
      functions in clinical practice with children across diagnoses, disabilities,
      ages, and genders. METHODS: A set of 57 codes were selected and worded to
      describe children's support needs in everyday life. Parents of children aged 1 to
      15 years participated in interviews to discuss and rate their child's disability.
      RESULTS: Of 367 invited parents, 332 (90.5%) participated. The mean age of their
      children with disability was 9.4 years. The mean code scores were 50.67, the
      corrected code-total correlations were .76, intercode correlations had the mean
      of 0.61, and Cronbach's alpha was .98. As a result of Rasch analysis, graphical
      data for disability measures paralleled clinical expectations across the total
      population of 332 children. CONCLUSION: The World Health Organization
      International Classification of Functioning, Disability and Health child and
      youth version d code data can provide a coherent measure of severity of
      disability in children across various diagnoses, ages, and genders.

PMID- 28503599
TI  - Is Chromosome 15q13.3 Duplication Involving CHRNA7 Associated With Oral Clefts?
AB  - Copy number variants have been associated with intellectual disability, multiple
      congenital anomalies and craniofacial disorders. It has been reported that
      microduplication of 15q13.3 is associated with autism, cognitive impairment,
      seizures, and attention-deficit hyperactivity disorder. Here, the author
      identified microduplications in the 15q13.3 region in 4 cases from 3 Chinese
      families using chromosomal microarray analysis-single nucleotide polymorphism
      array (CMA-SNP). These 4 cases include 2 fetuses from 2 unrelated families and a
      father and a daughter from a third family. The identified microduplications of
      15q13.3 are approximately 400 kb in size, encompassing just 1 gene, cholinergic
      receptor, neuronal nicotinic, alpha polypeptide 7 (CHRNA7). Three-fourths of the
      probands exhibit oral clefts, which has not been previously reported in cases
      with this duplication genotype. Therefore, in this study, the author describes
      for the first time the common feature of oral clefts in patients carrying a
      microduplication of 15q13.3 encompassing the CHRNA7 gene, which sheds light on
      the correlation between CHRNA7 and cleft palate.

PMID- 28503600
TI  - Delayed Effects of Transcutaneous Organophosphate Poisoning in Four Children.
AB  - Contamination or transcutaneous absorption of organophosphates (OP) is rare and
      there exist only few reports of such manner of poisoning. We report four children
      from the same family in whom temporal proximity of the disease onset, a detailed
      interrogation of parents and exclusion of other clinical differentials, led to
      the diagnosis of transcutaneous intoxication with organophosphates (diazinon).
      The contamination occurred during the game with a freshly used poison can.
      Uncommon clinical picture was marked by delayed signs predominantly reflecting
      certain nicotinic effects (muscle weakness, cramps) along with subtle neuropathic
      features occurring throughout a few weeks after initial event. Our illustrative
      cases can further contribute to the better awareness and understanding of
      variable spectrum of transcutaneous route of OP poisoning.

PMID- 28503601
TI  - Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis and Guillain
      Barre Syndrome in a 16-Month-Old Child.
AB  - A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic
      lymphohistiocytosis and transferred to our hospital on the 58th day of the
      hemophagocytic lymphohistiocytosis after treatment failure according to the
      Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital,
      she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a
      acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was
      established. Intravenous immunoglobulin G was started on the 57th day of the
      Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For
      hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen
      (pirarubicin, cyclophosphamide, vincristine, and prednisone) and 2 courses of
      ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase), we are now in
      the process of coordinating unrelated umbilical cord blood transplantation. To
      the best of our knowledge, we report the youngest case of Guillain-Barre syndrome
      accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid
      progression of Guillain-Barre syndrome, the electrophysiological subtype of
      Guillain-Barre syndrome, and treatment delay possibly led to poor neurological
      outcome.

PMID- 28503602
TI  - Clinical Profile of Pediatric Neurological Disorders: Outpatient Department,
      Khartoum, Sudan.
AB  - BACKGROUND: There is no available data from Sudan reflecting the magnitude of the
      neurological disorders and disabilities in the pediatric age-group. This study
      aims to evaluate the pattern of neurological disorders among Sudanese children.
      PATIENTS AND METHODS: This is a retrospective survey of children with epilepsy
      and other neurodisability disorders seen at pediatric neurology outpatient
      clinic, during the period from January 2007 to August 2013. The data of 9600
      patients were analyzed. RESULTS: A total of 6019 patients were included in the
      study. The majority of the patients had epilepsy that amounted to 52.8%, followed
      by cerebral palsy (19.1%), congenital anomalies of the central nervous system
      (6.2%), neuromuscular disorders (3.2%), stroke (2.4%), ataxia and movement
      disorders (1.9%), assumed genetic syndromes (1.2%), and others. CONCLUSION:
      Neurological disorders constitute a major cause of chronic morbidity in pediatric
      age-group.

PMID- 28503603
TI  - Vein of Galen Aneurysmal Malformation in Neonates Presenting With Congestive
      Heart Failure.
AB  - The authors report the case of a neonate presenting with signs of a congenital
      cardiac disease. Echocardiography showed a structural normal heart, right-to-left
      ductal flow, a dilated superior caval vein, and reversed diastolic flow in the
      proximal descending aorta. Brain magnetic resonance imaging showed a vein of
      Galen arteriovenous malformation. This highlights the importance of considering
      an intracranial cause in the differential diagnosis of neonatal congestive heart
      failure.

PMID- 28503604
TI  - A De Novo Mutation in MTND6 Causes Generalized Dystonia in 2 Unrelated Children.
AB  - Dystonia is often associated with the symmetrical basal ganglia lesions of Leigh
      syndrome. However, it has also been associated with mitochondrial ND mutations,
      with or without Leber hereditary optic neuropathy. The m.14459G>A mutation in ND6
      causes dystonia with or without familial Leber hereditary optic neuropathy. We
      report heteroplasmic 14459G>A mutations in 2 unrelated children with
      nonmaternally inherited generalized dystonia and showing bilateral magnetic
      resonance imaging lesions in nucleus pallidus and putamen. Both children have
      reached their teenage years, and they are intellectually active, despite their
      motor problems.

PMID- 28503605
TI  - Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a
      Neurodevelopmental Phenotype: A Case Report and Review of Literature.
AB  - The GRIN2B (glutamate receptor, ionotropic, N-methyl-d-aspartate 2B) gene,
      located in the short arm of chromosome 12, encoding the NR2B subunit of the N
      methyl-D-aspartate receptor, has recently been recognized to play an important
      role in corticogenesis and brain plasticity. Deletions in the short arm of
      chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in
      developmental delay, whereas gain of function leads to epilepsy, and infantile
      spasms in particular. In addition, GRIN2B variants have been associated with
      autism spectrum disorder and schizophrenia. Here the authors report a child with
      global developmental delay, autistic behavioural features, central hypotonia,
      dysmorphic features and isolated congenital anomalies of the fingers and toes,
      and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving
      loss of several genes, including GRIN2B. This report and our review of the
      literature help clarify the distinct phenotypes associated with loss or gain of
      GRIN2B function.

PMID- 28503607
TI  - Encephalopathy and Axonal Neuropathy Associated With Mycoplasma Pneumoniae
      Infection: Response to Intravenous Immunoglobulin Therapy.
AB  - Mycoplasma pneumoniae infection frequently presents as a self-limited process,
      however, severe cases and even fatalities have been reported. The authors present
      a case of Mycoplasma pneumoniae infection associated with both encephalopathy and
      peripheral neuropathy that responded to intravenous immunoglobulin therapy. To
      our knowledge, this is the first documented case of Mycoplasma pneumoniae related
      to encephalitis and peripheral axonal neuropathy. To date, there is insufficient
      data on the effect of intravenous immunoglobulin on the course of mycoplasma
      associated central nervous system/peripheral nervous system disease. While
      intravenous immunoglobulin has aided in a variety of autoimmune-mediated
      disorders, its efficacy in mycoplasma-mediated encephalitis treatment remains
      unclear. In this patient case, reversal of both central and peripheral nervous
      system symptoms after treatment with intravenous immunoglobulin suggested a
      possible therapeutic benefit.

PMID- 28503606
TI  - MECP2 Duplications in Symptomatic Females: Report on 3 Patients Showing the Broad
      Phenotypic Spectrum.
AB  - Xq28 microduplications including the MECP2 gene constitute a 100% penetrant X
      linked syndrome in males caused by overexpression of normal MeCP2 protein. A
      small number of cases of affected females have been reported. This can be due to
      the location of the duplicated material into an autosome, but it can also be due
      to the location of the duplicated material into one of the X chromosomes and
      random or unfavorable skewed X chromosome inactivation, which is much more likely
      to occur but may be underdiagnosed because of the resulting broad phenotypic
      spectrum. In order to contribute to the phenotypic delineation of Xq28
      microduplications including MECP2 in symptomatic females, the authors present
      clinical and molecular data on 3 patients illustrating the broad phenotypic
      spectrum. Our finding underlines the importance of quantitative analysis of MECP2
      in females with intellectual disability and raises the question of the indication
      in females with borderline intellectual performances or learning difficulties.

PMID- 28503608
TI  - Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and
      Epileptic Encephalopathy.
AB  - Hemimegalencephaly, a congenital brain malformation typically characterized by
      enlargement of one hemisphere, is frequently associated with intractable
      epilepsy. The authors report a case of a 12-month-old girl with
      hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly
      escalating seizures, arrested development, and associated encephalopathy. The
      brain tissue was examined and evaluated for neuroinflammation.
      Immunohistochemical analysis of the brain tissue revealed the presence of
      abundant activated CD68-positive microglia and reactive astrogliosis. Detection
      of active inflammatory changes in the brain of a patient with hemimegalencephaly
      complicated by intractable epilepsy suggests a potential role of ongoing brain
      inflammation in seizure exacerbation and epileptic encephalopathy.

PMID- 28503609
TI  - An Unusual Triad in Pediatric Neurology: A Case Report on Cerebral Palsy,
      Epilepsy, and Duchenne Muscular Dystrophy.
AB  - We present a case of an unusual triad in pediatric neurology: a currently 12-year
      old boy with cerebral palsy and epilepsy who was later also diagnosed with
      Duchenne muscular dystrophy. We describe the clinical path that resulted in this
      exceptional diagnosis. This case report illustrates how different neurological
      disorders may overshadow each other. In addition, it demonstrates that every
      child with cerebral palsy and either an atypical clinical course or with
      inexplicable laboratory values-as well as every infant boy born to a theoretical
      Duchenne muscular dystrophy carrier-should be subjected to additional
      investigations.

PMID- 28503610
TI  - Assessment of Subclinical Pancreatitis in Epileptic Children With Different
      Treatment Modalities.
AB  - Acute pancreatitis differ in pediatrics and adults. Drug-induced pancreatitis is
      one of the common causes of pancreatitis in children. This case-control study
      aimed to assess subclinical pancreatitis in patients with epilepsy treated with
      different drug regimens. Eighty known patients with epilepsy were enrolled. Forty
      patients were treated with monotherapy (group I) and 40 were treated with
      multitherapy (group II) regimens. Twenty age- and sex-matched healthy children
      were enrolled as control (group III). Serum lipase and amylase were assayed in
      all included children. Significant differences were found between groups I and
      III and between groups II and III regarding serum amylase and lipase (P < .001
      for all). Significant difference were found between groups I and II (P = .024)
      and between groups II and III (P = .01) regarding pancreatic duct and body
      diameters. Significant difference were found between patients with controlled and
      uncontrolled fits regarding serum amylase (P = .008). In conclusion, subclinical
      pancreatitis can complicate the treatment with different antiepileptic regimens.

PMID- 28503611
TI  - Acute Postviral Encephalopathy: Pathologic and Radiologic Correlation in an
      Atypical Case.
AB  - The authors report a case of fatal acute encephalopathy following influenza
      infection, with slightly atypical pathological and imaging findings. A healthy 8
      year-old boy with probable recent influenza A/B infection admitted for refractory
      seizures was placed on phenobarbital coma and later developed hemodynamic
      instability. Magnetic resonance imaging revealed bilateral cerebral and
      cerebellar white matter lesions and microhemorrhages. Following his demise, the
      autopsy revealed a large area of necrosis in the right centrum semiovale with
      similar lesions in the temporal and cerebellar regions. Microscopically, there
      was extensive coagulative necrosis, compatible with necrotizing white matter
      encephalopathy, and neuronal loss suggesting superimposed hypoxic-ischemia. The
      acute progressive neurologic deterioration was partly reminiscent on acute
      necrotizing encephalopathy, a condition recently associated with influenza A. In
      acute necrotizing encephalopathy, typical brain findings are characterized by
      bilateral thalamic necrosis/petechiae with variable white matter edema. The
      somewhat atypical findings in our case can relate to superadded cardiovascular
      collapse and hypoxic-ischemic effects.

PMID- 28503612
TI  - A Video Report of Brain-Lung-Thyroid Syndrome in a Japanese Female With a Novel
      Frameshift Mutation of the NKX2-1 Gene.
AB  - Benign hereditary chorea is a rare autosomal-dominant disorder that is
      characterized by childhood-onset nonprogressive chorea and normal cognitive
      function. Defects in NKX2-1 on chromosome 14q13, which encodes thyroid
      transcription factor 1, produce a concurrent clinical manifestation of chorea,
      respiratory distress, and hypothyroidism known as "brain-lung-thyroid syndrome."
      Here, the authors describe a video report of benign hereditary chorea in a
      Japanese female with a novel frameshift mutation of NKX2-1 (c.915_916insC)
      (p.Ala303ArgfsX132) that was initially misdiagnosed as ataxic cerebral palsy. In
      early infancy, especially before the appearance of chorea, benign hereditary
      chorea can be misdiagnosed as ataxic and dyskinetic cerebral palsy due to shared
      clinical features including motor delay, hypotonia, ataxic gait, and dystonia.

PMID- 28503613
TI  - A Mutation in the Tubulin-Encoding TUBB3 Gene Causes Complex Cortical
      Malformations and Unilateral Hypohidrosis.
AB  - Recent studies have emphasized the association between tubulin gene mutations and
      developmental abnormalities of the cortex. In this study, the authors identified
      a mutation in the tubulin-encoding class III beta-tubulin (TUBB3) gene in a 4
      year-old boy presenting with brain abnormalities and unilateral hypohidrosis. The
      patient showed a left internal strabismus, moderate developmental delay, and
      congenital hypohidrosis of the right side of the body. Magnetic resonance imaging
      disclosed gyral disorganization mainly in the left perisylvian region, dysmorphic
      and hypertrophic basal ganglia with fusion between the putamen and caudate
      nucleus without affecting the anterior limb of the internal capsule, and moderate
      hypoplasia of the right brain stem and cerebellum. Diffusion tensor imaging
      studies revealed disorganization of the pyramidal fibers. The amplitude of the
      sympathetic skin response was low in the right arm, which led to a diagnosis of
      focal autonomic neuropathy. Sequencing the TUBB3 gene revealed a de novo missense
      mutation, c.862G>A (p.E288K).

PMID- 28503614
TI  - De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis-Ptosis
      Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome.
AB  - Interstitial deletions affecting the long arm of chromosome 3 have been
      associated with a broad phenotype. This has included the features of
      blepharophimosis-ptosis-epicanthus inversus syndrome, Dandy-Walker malformation,
      and the rare Wisconsin syndrome. The authors report a young female patient
      presenting with features consistent with all 3 of these syndromes. This has
      occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2,
      ZIC1, and ZIC4. This patient provides further evidence for the role of ZIC1 and
      ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker
      malformation to have associated corpus callosum thinning. This patient is also
      only the seventh to be reported with the rare Wisconsin syndrome phenotype.

PMID- 28503615
TI  - Neural Correlates of Reward Processing in Typical and Atypical Development.
AB  - Atypically developing children including those born preterm or who have autism
      spectrum disorder can display difficulties with evaluating rewarding stimuli,
      which may result from impaired maturation of reward and cognitive control brain
      regions. During functional magnetic resonance imaging, 58 typically and
      atypically developing children (6-12 years) participated in a set-shifting task
      that included the presentation of monetary reward stimuli. In typically
      developing children, reward stimuli were associated with age-related increases in
      activation in cognitive control centers, with weaker changes in reward regions.
      In atypically developing children, no age-related changes were evident.
      Maturational disturbances in the frontostriatal regions during atypical
      development may underlie task-based differences in activation.

PMID- 28503616
TI  - Pediatric Hereditary Neuralgic Amyotrophy: Successful Treatment With Intravenous
      Immunoglobulin and Insights Into SEPT9 Pathogenesis.
AB  - Hereditary neuralgic amyotrophy is a rare disorder characterized by the sudden
      onset of recurrent episodes of painful brachial plexus neuropathies, followed by
      atrophy within a few weeks. The authors present the case of a 5-year-old boy who
      developed hereditary neuralgic amyotrophy in the right upper limb after a
      gastroenteritis illness. He made a full and rapid recovery with the use of
      intravenous immunoglobulin. A subsequent episode in the left upper limb during
      the course of intravenous immunoglobulin was significantly attenuated. A de novo
      c.262C>T mutation in exon 2 of the SEPT9 gene was identified. To our knowledge,
      he is the first pediatric patient with SEPT9 hereditary neuralgic amyotrophy to
      be treated with intravenous immunoglobulin. The authors hypothesize that the
      c.262C>T mutation in exon 2 of the SEPT9 gene generates pathology via the
      numerous isoforms under specific conditions and that intravenous immunoglobulin
      can play a role at the epigenetic level of improving dysfunctional SEPT9
      expression.

PMID- 28503617
TI  - Further Validation of the SIGMAR1 c.151+1G>T Mutation as Cause of Distal
      Hereditary Motor Neuropathy.
AB  - Distal hereditary motor neuropathies represent a group of rare genetic disorders
      characterized by progressive distal motor weakness without sensory loss. Their
      genetic heterogeneity is high and thus eligible for diagnostic whole exome
      sequencing. The authors report successful application of whole exome sequencing
      in diagnosing a second consanguineous family with distal hereditary motor
      neuropathy due to a homozygous c.151+1G>T variant in SIGMAR1. This variant was
      recently proposed as causal for the same condition in a consanguineous Chinese
      family. Compared to this family, the Afghan ethnic origin of our patient is
      distinct, yet the features are identical, validating the SIGMAR1 deficiency
      phenotype: progressive muscle wasting/weakness in lower and upper limbs without
      sensory loss. Rapid disease progression during adolescent growth is similar and
      may be due to SIGMAR1's role in regulating axon elongation and tau
      phosphorylation. Finally, the authors conclude that SIGMAR1 deficiency should be
      added to the differential diagnosis of distal hereditary motor neuropathies.

PMID- 28503618
TI  - Occipital Bony Abnormality and Multiple Strokes in a Pediatric Patient: Case
      Report and Review of the Current Literature.
AB  - This study presents a case of a 15-year-old boy who had a right vertebral artery
      dissection with distal embolization from repeated trauma from an occipital bony
      spicule. The authors hypothesize that this bony spicule was contacting the left
      vertebral artery during head rotation, resulting in trauma to the vessel and
      formation of emboli which then showered distally, causing strokes in the
      posterior circulation of the brain. This specific phenomenon has previously been
      reported three times, only one of which was in pediatric literature. It is
      important for individuals to be aware of this rare anatomic cause of vertebral
      artery dissection in patients presenting with an odd constellation of symptoms
      related to strokes from vertebro-basilar system. Treatment options including
      early intervention with intravascular coil embolization are also discussed.

PMID- 28503619
TI  - Seizures Related to Hypomagnesemia: A Case Series and Review of the Literature.
AB  - OBJECTIVE: Childhood seizures have various nonneurological etiologies. The
      patient's magnesium levels should be measured when evaluating afebrile seizures.
      The purpose of the current case series is to describe a systematic approach for
      diagnosing hypomagnesemia using 3 recent patient cases. METHODS: This case series
      describes 3 patients with unprovoked hypomagnesemia-associated seizures. The
      authors describe the differential diagnosis, pathophysiology, and the workup of
      hypomagnesemia-associated seizures. RESULTS: Hypomagnesemia contributed to the
      cause of the seizures in all 3 cases. Various causes of hypomagnesemia were
      investigated, including genetic etiologies. All 3 patients were maintained at a
      magnesium level >0.65 mmol/L, which improved or eliminated the seizures.
      SIGNIFICANCE: Magnesium levels should always be measured when trying to determine
      the etiology of seizures. Hypomagnesemia and afebrile seizures should be treated
      with the goal of maintaining a magnesium concentration >0.65 mmol/L. Although
      rare, genetic causes of hypomagnesemia should be considered, once common causes
      of hypomagnesemia are ruled out.

PMID- 28503620
TI  - Complex Phenotype of a Boy With De Novo 16p13.3-13.2 Interstitial Deletion.
AB  - Interstitial deletions encompassing chromosome 16p13.3-13.2 are rarely described
      in the literature, whereas terminal deletions or duplications involving this
      region are slightly more frequently described. The authors describe a boy
      harboring a de novo 16p13.3-13.2 interstitial deletion, with intellectual
      disability, verbal dyspraxia, epilepsy, and a distinctive brain magnetic
      resonance finding, namely a nodular heterotopia. The authors found partial
      genotype-phenotype correspondences regarding epilepsy and intellectual
      disability, which have been associated with 16p1 region. Conversely, nodular
      heterotopia and verbal dyspraxia have not been clearly related to this region.
      These data are in agreement with the emerging concept that similar copy number
      variants may be the general risk factors for distinct disorders. Verbal
      dyspraxia, which has not responded to speech therapy, is the child's most
      disabling trait. In view of the above, genetic studies should be appraised in
      cases of serious speech difficulties, especially if they are associated with
      intellectual disability and epilepsy.

PMID- 28503621
TI  - Pelvic-Spinal Analysis and the Impact of Onabotulinum toxin A Injections on
      Spinal Balance in one Child With Cerebral Palsy.
AB  - BACKGROUND: In children with cerebral palsy, primary (eg, abnormal muscle tone
      and weakness) and secondary impairments (eg, contractures) can modify pelvic
      spinal alignment. The main aim of this article was to establish a new approach to
      pelvic-spinal analysis in children with cerebral palsy, taking into account the
      whole pelvis-spine complex, illustrated by a case study. METHODS: This is a case
      study of an ambulatory child with cerebral palsy (spastic diplegia) who underwent
      analysis of the pelvic-spine complex from X-ray images taken in standing position
      from C2 to the proximal femur. Pelvic shape was characterized by the pelvic
      incidence angle, which is the sum of sacral slope and pelvic tilt, before and
      after the treatment by regular onabotulinumtoxinA injections into the hip
      flexors, and the use of soft lumbar brace over 5 years. RESULTS: The sagittal
      balance of the spine was improved following the treatment, with a reduction in
      lumbar lordosis and sacral slope. The reduction in lumbar hyperextension likely
      reduced the risk of spondylolysis, low back pain, and degenerative
      spondylolisthesis in adulthood. CONCLUSION: A biomechanical approach to the
      evaluation of the pelvic-spinal complex offers new perspectives to increase the
      understanding of spinal balance in children with cerebral palsy, providing more
      options for treatment, such as onabotulinumtoxinA.

PMID- 28503622
TI  - Stiff-Person Syndrome and Graves' Disease: A Pediatric Case Report.
AB  - A 9-year-old female child presented with a history of falls, weight loss, diffuse
      leg pain, and progressive gait disorder, following 1 previous event described as
      a tonic-clonic seizure. She had increased thyroid volume, brisk symmetric
      reflexes, abnormal gait, and painful spasms of the paraspinal musculature.
      Thyroid function tests indicated biochemical hyperthyroidism, and thyrotropin
      receptor antibodies were positive. Her electromyography showed continuous
      activation of normal motor units of the paraspinal and proximal lower extremity
      muscles. The patient had a diagnosis of Graves' disease with associated stiff
      person syndrome, with elevated anti-glutamic acid decarboxylase antibody levels.
      After intravenous immunoglobulin therapy, her ambulation was substantially
      improved and the symptoms of stiff-person syndrome decreased dramatically.

PMID- 28503623
TI  - Seven-Digit Creatine Kinase in Acute Rhabdomyolysis in a Child.
AB  - Rhabdomyolysis is an acute life-threatening condition that can occur in childhood
      secondary to many causes. The authors report the case of a 3-year-old male child
      who presented with acute rhabdomyolysis. The peak plasma creatine kinase level
      was extremely high. The 2 main causes of rhabdomyolysis in childhood are viral
      myositis and trauma, which can sometimes lead to acute renal failure. The highest
      creatine kinase levels reported in the literature so far was a 6-digit level in
      2014 case report. In this study, the authors report the case of a 7-digit
      creatine kinase level in a child secondary to viral myositis who did not require
      renal dialysis.

PMID- 28503624
TI  - Temporary Efficacy of Pyrimethamine in Juvenile-Onset Tay-Sachs Disease Caused by
      2 Unreported HEXA Mutations in the Indian Population.
AB  - BACKGROUND: Juvenile Tay-Sachs disease is rarer than other forms of Tay-Sachs
      disease and is usually seen in children between the age of 2 and 10 years.
      Pyrimethamine as a pharmacological chaperone was used to increase beta
      hexosaminidase A activity in this patient. PATIENT: We describe a patient with
      Tay-Sachs disease from the Indian population, a juvenile case who presented with
      developmental regression starting at the age of three, initially with motor
      followed by language regression. She is currently incapacitated with severe
      behavioral issues. CONCLUSION: This brief communication gives an insight into the
      efficacy of pharmacological chaperones. It also describes two unreported
      mutations in hexosaminidase A gene from the Indian population. After commencing
      Pyrimethamine, though initial benefits with increase in levels corresponded with
      briefly halting the motor regression, the observed increase was only transient
      and not associated with discernible beneficial neurological or psychiatric
      effects.

PMID- 28503625
TI  - Maternal Race-Ethnicity, Immigrant Status, Country of Birth, and the Odds of a
      Child With Autism.
AB  - The risk of autism spectrum disorder varies by maternal race-ethnicity,
      immigration status, and birth region. In this retrospective cohort study, Western
      Australian state registries and a study population of 134 204 mothers enabled us
      to examine the odds of autism spectrum disorder with intellectual disability in
      children born from 1994 to 2005 by the aforementioned characteristics. We
      adjusted for maternal age, parity, socioeconomic status, and birth year.
      Indigenous women were 50% less likely to have a child with autism spectrum
      disorder with intellectual disability than Caucasian, nonimmigrant women.
      Overall, immigrant women were 40% less likely to have a child with autism
      spectrum disorder with intellectual disability than nonimmigrant women. However,
      Black women from East Africa had more than 3.5 times the odds of autism spectrum
      disorder with intellectual disability in their children than Caucasian
      nonimmigrant women. Research is implicated on risk and protective factors for
      autism spectrum disorder with intellectual disability in the children of
      immigrant women.

PMID- 28503626
TI  - The Effect of Noninvasive Positive Pressure Ventilation on Pneumonia
      Hospitalizations in Children With Neurological Disease.
AB  - The aim of this retrospective single-institution observational study was to
      identify whether the frequency of hospitalizations for pneumonia would change
      before and after the initiation of noninvasive positive pressure ventilation in
      children with neurological conditions. Included patients were 1 to 18 years old
      with an underlying neurological disease and had been prescribed nocturnal
      noninvasive positive pressure ventilation. The authors excluded patients with a
      tracheostomy or those who used noninvasive positive pressure ventilation solely
      for obstructive sleep apnea. A total of 14 patients were included in the study,
      among whom there was no significant change in the mean number of pneumonias 2
      years before versus after the initiation of noninvasive positive pressure
      ventilation (mean difference = -0.714, standard deviation = 2.4, P = .312). These
      findings suggest that while noninvasive positive pressure ventilation may not
      reduce absolute pneumonia frequency, it may have the beneficial value of
      preventing an increase in the frequency of pneumonias over time, especially in
      children with progressive respiratory compromise.

PMID- 28503627
TI  - Two Novel KCNQ2 Mutations in 2 Families With Benign Familial Neonatal
      Convulsions.
AB  - Benign familial neonatal convulsion is a rare autosomal dominant inherited
      epilepsy syndrome characterized by unprovoked seizures in the first few days of
      life, normal psychomotor development, and a positive intergenerational family
      history of neonatal seizures. Over 90% of the affected individuals have inherited
      causal mutations in KCNQ2, which encodes for the potassium voltage-gated channel
      subfamily Q, member 2. Mutations in KCNQ2 are also associated with a severe
      neonatal encephalopathy phenotype associated with poor seizure control and
      neurodevelopmental deficits. The authors report the clinical presentations,
      response to medication, and intrafamilial phenotypic variability in 2 families
      with benign familial neonatal convulsions, carrying previously unreported
      heterozygous missense mutations, c.1066C>G (p.Leu356Val) and c.1721G<A
      (p.Gly574Asp), in KCNQ2. The cases reported herein suggest that inherited
      missense mutations in KCNQ2 can be associated with an intermediate phenotype and
      illustrate the challenges associated with prognosis and counselling for
      individuals with inherited missense mutations in KCNQ2.

PMID- 28503628
TI  - Visceral Hyperalgesia: When to Consider Gabapentin Use in Neonates-Case Study and
      Review.
AB  - Visceral hyperalgesia refers to increased pain sensation in response to
      gastrointestinal sensory stimulus. In neonates with neurological impairments,
      gabapentin has been successfully used as a treatment for visceral hyperalgesia in
      neonates. The authors describe a preterm infant with myelomeningocele and
      persistent neuropathic pain that manifested as irritability, hypertonicity, poor
      weight gain, and feeding intolerance. After exclusion of other etiologies, the
      diagnosis of visceral hyperalgesia was suspected and the infant was treated with
      gabapentin. Following appropriate titration to effect and close monitoring of
      side effects of gabapentin, he subsequently demonstrated improved tone, decreased
      irritability with feedings, and appropriate weight gain. In addition, the authors
      provide a review of the available literature of gabapentin use in neonates and
      offer suggestions on when to consider starting gabapentin in a neonate with
      neurological impairment and chronic unexplained gastrointestinal manifestations.

PMID- 28503629
TI  - Hyperostosis Frontalis Interna in a Child With Severe Traumatic Brain Injury.
AB  - Hyperostosis frontalis interna is an unexplained irregular thickening of the
      inner table of the frontal bone. Hyperostosis frontalis interna was first
      identified in 1719 by Morgagni as a symptom of a more generalized syndrome
      characterized by virilism and obesity. Most current studies have shown
      hyperostosis frontalis interna to be a sex- and age-dependent phenomenon, and
      females manifest a significantly higher prevalence of hyperostosis frontalis
      interna than males. In this article, the authors report the clinical case of
      hyperostosis frontalis interna in a 7-year-old child who had severe traumatic
      brain injury in the past; review the related literature; and discuss the
      clinical, radiological, and therapeutic features of this condition.

PMID- 28503630
TI  - Defect-mediated phonon dynamics in TaS2 and WSe2.
AB  - We report correlative crystallographic and morphological studies of defect
      dependent phonon dynamics in single flakes of 1T-TaS2 and 2H-WSe2 using selected
      area diffraction and bright-field imaging in an ultrafast electron microscope. In
      both materials, we observe in-plane speed-of-sound acoustic-phonon wave trains,
      the dynamics of which (i.e., emergence, propagation, and interference) are
      strongly dependent upon discrete interfacial features (e.g., vacuum/crystal and
      crystal/crystal interfaces). In TaS2, we observe cross-propagating in-plane
      acoustic-phonon wave trains of differing frequencies that undergo coherent
      interference approximately 200 ps after initial emergence from distinct
      interfacial regions. With ultrafast bright-field imaging, the properties of the
      interfering wave trains are observed to correspond to the beat frequency of the
      individual oscillations, while intensity oscillations of Bragg spots generated
      from selected areas within the region of interest match well with the real-space
      dynamics. In WSe2, distinct acoustic-phonon dynamics are observed emanating and
      propagating away from structurally dissimilar morphological discontinuities
      (vacuum/crystal interface and crystal terrace), and results of ultrafast selected
      area diffraction reveal thickness-dependent phonon frequencies. The overall
      observed dynamics are well-described using finite element analysis and time
      dependent linear-elastic continuum mechanics.

PMID- 28503631
TI  - Stacking order dynamics in the quasi-two-dimensional dichalcogenide 1T-TaS2
      probed with MeV ultrafast electron diffraction.
AB  - Transitions between different charge density wave (CDW) states in quasi-two
      dimensional materials may be accompanied also by changes in the inter-layer
      stacking of the CDW. Using MeV ultrafast electron diffraction, the out-of-plane
      stacking order dynamics in the quasi-two-dimensional dichalcogenide 1T-TaS2 is
      investigated for the first time. From the intensity of the CDW satellites aligned
      around the commensurate l = 1/6 characteristic stacking order, it is found out
      that this phase disappears with a 0.3 ps time constant. Simultaneously, in the
      same experiment, the emergence of the incommensurate phase, with a slightly
      slower 2.0 ps time constant, is determined from the intensity of the CDW
      satellites aligned around the incommensurate l = 1/3 characteristic stacking
      order. These results might be of relevance in understanding the metallic
      character of the laser-induced metastable "hidden" state recently discovered in
      this compound.

PMID- 28503632
TI  - Ultrafast X-ray diffraction probe of terahertz field-driven soft mode dynamics in
      SrTiO3.
AB  - We use ultrafast X-ray pulses to characterize the lattice response of SrTiO3 when
      driven by strong terahertz fields. We observe transient changes in the
      diffraction intensity with a delayed onset with respect to the driving field.
      Fourier analysis reveals two frequency components corresponding to the two lowest
      energy zone-center optical modes in SrTiO3. The lower frequency mode exhibits
      clear softening as the temperature is decreased while the higher frequency mode
      shows slight temperature dependence.

PMID- 28503633
TI  - Reactive Oxygen Species and Serous Epithelial Ovarian Adenocarcinoma.
AB  - Serous ovarian cancer (SOC) is usually diagnosed at late stage and stage-adjusted
      five year survival rate is low. Mortality is relatively heavy on African
      Americans/Black (AA) affected with SOC compared to their Caucasian counterparts,
      though the cause for the disparity remains unclear. DNA damage induced by
      oxidative stress has been linked to ovarian cancer, but the role of oxidative
      stress in distinguishing differences in aggressive SOC tumors among patients is
      yet to be determined. This study aims to determine the levels of reactive oxygen
      species (ROS), malondialdehyde (MDA), reactive carbonyl groups and antioxidants
      in primary SOC normal, precancerous (cystadenoma, borderline) and invasive
      (III/IV) tissue samples obtained from AA and Caucasian subgroups. Additionally,
      the study seeks to investigate significant changes in the level of ROS between AA
      and Caucasian SOC samples. A fluorogenic probe, dichlorodihydrofluorescein (DCFH
      DiOxyQ), was used to scavenge reactive oxygen species in SOC normal, precancerous
      and malignant stages III/IV tissue samples. Malondialdehyde (MDA), a lipid
      peroxidation marker, and reactive carbonyl groups were measured as indicators of
      oxidative injury. Moreover, antioxidant status was assessed by estimating
      glutathione peroxidase 3 (GPX3) enzyme levels. Results indicate ROS concentration
      was approximately 96% higher in the malignant tissues in comparative to the
      normal non-diseased controls. In addition, ROS concentration among AA women was
      approximately 9% higher than Caucasian women. MDA levels increased exponentially
      from non-disease control and precancerous tissues relative to malignant tissues.
      Furthermore, malignant serous ovarian samples showed significantly higher
      reactive carbonyl content compared to the non-disease controls (p=0.009), while
      GPX3 levels decreased considerably in serous cystadenoma and malignant tissue
      samples, and non-diseased control compared to borderline disease. The results
      suggest accumulation of ROS and MDA levels may be a causative factor for SOC.
      Elevated levels of MDA and reactive carbonyl proteins could override the GPX3
      enzyme capacity therefore, initiating serous ovarian neoplasm.

PMID- 28503634
TI  - An Acute Mouse Spinal Cord Slice Preparation for Studying Glial Activation ex
      vivo.
AB  - Pathological conditions such as amyotrophic lateral sclerosis, spinal cord injury
      and chronic pain are characterized by activation of astrocytes and microglia in
      spinal cord and have been modeled in rodents. In vivo imaging at cellular level
      in these animal models is limited due to the spinal cord's highly myelinated
      funiculi. The preparation of acute slices may offer an alternative and valuable
      strategy to collect structural and functional information in vitro from dorsal,
      lateral and ventral regions of spinal cord. Here, we describe a procedure for
      preparing acute slices from mouse spinal cord (Garre et al., 2016). This
      preparation should allow further understanding of how glial cells in spinal cord
      respond acutely to various inflammatory challenges.

PMID- 28503635
TI  - Efficient, Convergent SENSE MRI Reconstruction for Nonperiodic Boundary
      Conditions via Tridiagonal Solvers.
AB  - Undersampling is an effective method for reducing scan acquisition time for MRI.
      Strategies for accelerated MRI such as parallel MRI and Compressed Sensing MRI
      present challenging image reconstruction problems with non-differentiable cost
      functions and computationally demanding operations. Variable splitting (VS) can
      simplify implementation of difficult image reconstruction problems, such as the
      combination of parallel MRI and Compressed Sensing, CS-SENSE-MRI. Combined with
      augmented Lagrangian (AL) and alternating minimization strategies, variable
      splitting can yield iterative minimization algorithms with simpler auxiliary
      variable updates. However, arbitrary variable splitting schemes are not
      guaranteed to converge. Many variable splitting strategies are combined with
      periodic boundary conditions. The resultant circulant Hessians enable ??(n log n)
      computation but may compromise image accuracy at the spatial boundaries. We
      propose two methods for CS-SENSE-MRI that use regularization with non-periodic
      boundary conditions to prevent wrap-around artifacts. Each algorithm computes one
      of the resulting variable updates efficiently in ??(n) time using a
      parallelizable tridiagonal solver. AL-tridiag is a VS method designed to enable
      efficient computation for non-periodic boundary conditions. Another proposed
      algorithm, ADMM-tridiag, uses a similar VS scheme but also ensures convergence to
      a minimizer of the proposed cost function using the Alternating Direction Method
      of Multipliers (ADMM). AL-tridiag and ADMM-tridiag show speeds competitive with
      previous VS CS-SENSE-MRI reconstruction algorithm AL-P2. We also apply the
      tridiagonal VS approach to a simple image inpainting problem.

PMID- 28503636
TI  - The Various Roles of Oncology Nurse Specialists: An International Perspective.
AB  - Ilana Kadmon, PhD, RN was for many years a nurse specialist in Breast Cancer at
      Hadassah Medical Center, Jerusalem, Israel. From 2016, she started the role of a
      nurse academic consultant at the nursing division at Hadassah. Her PhD is from
      The University of Edinburgh, UK. Her research involved psychosocial aspects of
      breast cancer, and the role of the breast care nurse (BCN). She was a pioneer in
      developing the post of the BCN in Israel. This position was initially developed
      by her at Hadassah and initiated by the Israel Cancer Association. Beyond her
      clinical expertise, at the Hadassah School of Nursing, she lectures and writes in
      many areas on breast cancer care in general. She served as a board member of the
      European Oncology Nursing Society, and was also a member of the Editorial
      Committee of the European Journal of Oncology Nursing. Moreover, she serves as a
      reviewer for many nursing journals. She was involved in a mutual international
      collaborative project with nurses in Tianjin, China. She was there for seminars
      and initiated some cross-cultural research in the area of partners of women with
      breast cancer, involving both countries. Moreover, she has been invited to
      Cyprus, Greece Russia, and Turkey to teach and give workshops.

PMID- 28503637
TI  - Transforming Cancer Survivorship Care: An Australian Experience.

PMID- 28503638
TI  - The Advancement of Nurses is the Advancement of Medicine: A Personal Experience
      from Israel.

PMID- 28503639
TI  - Hepatocellular Carcinoma: Implications for Asia-Pacific Oncology Nurses.
AB  - Hepatocellular carcinoma (HCC) is a prominent malignancy in the Asia-Pacific
      region. Despite considerable knowledge about it's scope and nature this
      malignancy remains incurable. This manuscript reviews the epidemiology of this
      cancer, its pathogenesis, risk factors, potential prevention, surveillance,
      treatment, and the oncology nurses' role relative to this malignancy. A
      literature search from the past decade was performed using the PubMed and CINAHL
      databases using the search terms "hepatocellular carcinoma," "Asia," and "nursing
      issues". Themes such as etiology, prevention, treatment, and prognosis were
      included in this synthesis which has particular relevance to oncology nurses
      within the Asia-Pacific region.

PMID- 28503640
TI  - Breast Cancer Screening Practices and Related Health Beliefs among Taiwanese
      Nurses.
AB  - OBJECTIVE: Breast cancer is one of most common cancer types among women in
      Taiwan. Nurses are in an ideal position to promote breast cancer screening and
      educate individuals about breast health-related issues. This exploratory study
      aims to provide preliminary information on Taiwanese nurses' beliefs about breast
      cancer, breast cancer-related knowledge, and their cancer screening practices.
      METHODS: In this cross-sectional study, a total of 96 nurses completed self
      report questionnaires. RESULTS: Participants were knowledgeable about the
      different breast cancer screening modalities and the risk factors for breast
      cancer, but various misconceptions about breast cancer were still observed.
      Nevertheless, more than 50% of participants reported that they never had clinical
      breast examinations, ultrasound, and/or mammography screening in the past.
      CONCLUSIONS: Our study sample demonstrated greater knowledge on modalities of
      breast cancer screening modalities and the risk factors for breast cancers but
      lower screening practices. Future studies that examine the impact of demographics
      and the reinforcing and inhibiting factors related to nurses' screening uptake
      are warranted.

PMID- 28503641
TI  - The Role of a Nurse Specialist in Palliative Care: An Israeli Experience.
AB  - Given the severe shortage of physicians in Israel, the Ministry of Health issued
      a decree that offered advanced authority and responsibilities to experienced
      nurses; thus, the status of the nurse specialist (NS) was created. The role of NS
      in Israel is truly varied, incorporating many different facets that range from
      stabilizing to changing the existing palliative care (PC) orders, including those
      involving dosages and methods of care provision, issuing of repeat prescriptions,
      suspending drug treatment, and prescribing new drugs for a patient according to a
      protocol issued by a physician. The NS is also authorized to perform many
      clinical duties that frequently involve direct patient care. According to the
      different needs of the patients, he/she coordinates with the different members of
      the interdisciplinary team, who may be suitable to offer further help and support
      to the client and/or his/her significant others. His/her work keeps him/her in a
      constant dialogue with other health-care professionals, and as questions arise,
      he/she answers them and offers support to staff, patients, and family members. In
      the Middle East, the whole issue of PC is relatively new, and due to cultures,
      traditions, and religions, a number of difficulties have to be resolved.

PMID- 28503642
TI  - Vulvar and Vaginal Graft versus Host Disease: A Healthcare Clinic Initiative.
AB  - OBJECTIVE: In patients receiving bone marrow transplantation (BMT), their mucosa
      becomes altered and sclerotic changes in the female external genital organs
      occur. Although a few studies have specifically addressed vulvar and vaginal
      graft versus host disease (VVGvHD) and its repercussions on the sexual health and
      quality of life of patients, VVGvHD can be overlooked by health practitioners.
      The objective of the study is to describe the initiation of a health care clinic
      specializing in VVGvHD in a general tertiary hospital. METHODS: A VVGvHD clinic
      was founded as a part of BMT daycare in a joint initiative of the nursing staff
      and the medical director of the department and a gynecologist specializing in
      vulva and vaginal disease. Patients were assessed for vulvovaginal symptoms, such
      as dryness, burning, itching, pain to touch, pain during intercourse, and
      dysuria. These patients might be subsequently referred to the VVGvHD clinic
      according to their needs assessed by daycare nurses. Treatment guidelines were
      developed by the specialist gynecologist. RESULTS: A total of 81 women aged 2-66
      years (median age = 38 years) visited the clinic from 2009 to 2015. Of these
      women, 70 received an allogeneic transplant and 11 underwent autologous
      transplantation before consultation in our clinic. VVGvHD was detected in 54% of
      the patients. CONCLUSIONS: The VVGvHD clinic was developed to fulfill the
      specific needs of female patients who underwent BMT. The pioneer clinic was
      founded as a joint effort of the multidisciplinary team. Evidence supporting the
      optimum treatment for this condition is insufficient. This was the main reason
      for performing this study to explore the clinic that was newly based in Israel.
      VVGvHD may be a fluctuating condition with frequent deterioration and
      improvement. Therefore, regular clinical examinations are necessary.

PMID- 28503643
TI  - Doing the Dirty Work: Who Handles Antineoplastic Drug Contaminated Excreta and do
      They Do It Safely?

PMID- 28503644
TI  - What's the Buzz: Tell Me What's Happening in Breast Cancer Screening.
AB  - Many controversies have come to light related to breast cancer screening
      recommendations for average- and high-risk populations. This manuscript focuses
      on factors to consider when coordinating and conducting breast cancer screening
      programs in an average or "healthy women" population. As presented at the 2016
      ONS Congress, a brief comparison of current screening recommendations among
      various organizations for early detection of breast cancer is provided. Lessons
      learned regarding key components of successful screening programs such as being
      patient focused, accessible, and sustainable are shared. Practice implications
      such as gaining confidence in providing individualized patient education,
      encouraging every woman to discuss her risk of breast cancer with her health-care
      provider, advocating for patients needs and being involved in or aware of
      clinical and translational research on the efficacy of the clinical breast
      examination and screening services are critical roles for nurses and advanced
      practice nurse providers.

PMID- 28503645
TI  - Immune Checkpoint Inhibitors: An Innovation in Immunotherapy for the Treatment
      and Management of Patients with Cancer.
AB  - Cancer survival rates are generally increasing in the United States. These trends
      have been partially attributed to improvement in therapeutic strategies. Cancer
      immunotherapy is an example of one of the newer strategies used to fight cancer,
      which primes or activates the immune system to produce antitumor effects. The
      first half of this review paper concisely describes the cell mechanisms that
      control antitumor immunity and the major immunotherapeutic strategies developed
      to target these mechanisms. The second half of the review discusses in greater
      depth immune checkpoint inhibitors that have recently demonstrated tremendous
      promise for the treatment of diverse solid tumor types, including melanoma, non
      small cell lung cancer, and others. More specifically, the mechanisms of action,
      side effects, and patient and family management and education concerns are
      discussed to provide oncology nurses up-to-date information relevant to caring
      for cancer-affected patients treated with immune checkpoint inhibitors. Future
      directions for cancer immunotherapy are considered.

PMID- 28503646
TI  - Unmet Supportive Care Needs Among Informal Caregivers of Patients with Cancer:
      Opportunities and Challenges in Informing the Development of Interventions.

PMID- 28503647
TI  - Quality of Life and Its Determinants in Adult Cancer Patients Undergoing
      Chemotherapy Treatment in Pakistan.
AB  - OBJECTIVE: Cancer is a leading cause of death worldwide. Likewise, in Pakistan,
      it is a major health problem, with an approximate increase each year. Cancer
      treatment, particularly chemotherapy, produces a detrimental effect on
      individuals' well-being. Since the past few years, quality of life (QOL) is
      considered as the primary goal of cancer treatment in patients' survival. This
      study aimed to assess the QOL and its determinants in adult cancer patients
      undergoing chemotherapy treatment. METHODS: An analytical cross-sectional design
      was employed to achieve the study objectives, utilizing consecutive sampling
      technique. A total of 150 adult (>19 years) cancer patients were recruited from a
      Tertiary Care Hospital in Karachi, Pakistan. The data were collected using the
      Functional Assessment of Cancer Therapy-General, a QOL questionnaire. Multiple
      linear regression was run to determine the effect of predictor variables, with a
      mean QOL score. RESULTS: The overall mean score of QOL as 57.37. The domains of
      physical and emotional well-being were mainly affected by the chemotherapy
      treatment. Variables such as no previous hospitalization and no significant
      changes in life events were positively associated with the QOL. On the other
      hand, being female, unemployed, chemotherapy side effects (>1 week), impaired
      socialization, and discrimination by family/relatives were negatively associated
      with the QOL. CONCLUSIONS: The study findings suggested an overall low QOL among
      adult cancer patients undergoing chemotherapy treatment. It is recognized as a
      stressful treatment, which adversely affects the QOL of cancer patients.
      Interventions should focus on both the physical and psychological issues and need
      to be addressed to improve the QOL of adult cancer patients.

PMID- 28503648
TI  - Significance of Psychological Stress Response and Health-related Quality of Life
      in Spouses of Cancer Patients When Given Bad News.
AB  - OBJECTIVE: This study illuminates the degree of psychological stress response
      experienced by spouses of cancer patients when given bad news at three different
      times (notification of the name of the disease, notification of recurrence, and
      notification of terminality) as well as the factors that influence the response
      and the health status of the spouse as measured by health-related quality of life
      (QOL). METHODS: A total of 203 individuals (57 men and 146 women) who had
      received the three types of news were surveyed using a self-report questionnaire
      on psychological stress response, marital satisfaction, and health-related QOL
      scales. RESULTS: The degree of the psychological stress response was the highest
      for notification of terminality, followed by notification of the name of the
      disease, and notification of recurrence. The influencing factors varied depending
      on the notification period. Although no significant difference was observed for
      health-related QOL among the three notification types, significant differences
      were observed for certain items when compared with national standard values.
      CONCLUSIONS: When a notification of terminality, which produced the highest
      psychological stress response, is given, providing care that considers health
      related QOL is necessary not only for patients but also for their spouses.

PMID- 28503649
TI  - Reliability and Validity Study of a Tool to Measure Cancer Stigma: Patient
      Version.
AB  - OBJECTIVE: The aim of this methodological study is to establish the validity and
      reliability of the Turkish version of "A Questionnaire for Measuring Attitudes
      toward Cancer (Cancer Stigma) - Patient version." METHODS: The sample comprised
      oncology patients who had active cancer treatment. The construct validity was
      assessed using the confirmatory and exploratory factor analysis. RESULTS: The
      mean age of the participants was 54.9+/-12.3 years. In the confirmatory factor
      analysis, fit values were determined as comparative fit index = 0.93, goodness of
      fit index = 0.91, normed-fit index=0.91, and root mean square error of
      approximation RMSEA = 0.09 (P <0.05) (Kaiser-Meyer-Olkin = 0.88, chi2 = 1084.41,
      Df = 66, and Barletta's test P <0.000). The first factor was "impossibility of
      recovery and experience of social discrimination" and the second factor was
      "stereotypes of cancer patients." The two-factor structure accounted for 56.74%
      of the variance. The Cronbach's alpha value was determined as 0.88 for the two
      factor scale. CONCLUSIONS: "A questionnaire for measuring attitudes toward cancer
      (cancer stigma) - Patient version" is a reliable and valid questionnaire to
      assess stigmatization of cancer in cancer patients.

PMID- 28503650
TI  - Hand-held Fan Airflow Stimulation Relieves Dyspnea in Lung Cancer Patients.
AB  - OBJECTIVE: The main symptom of lung cancer is dyspnea which can lead to
      depression, anxiety, limited independent activities, and decreased quality of
      life. The purpose of this study was to identify the effect of airflow stimulation
      from a hand-held fan as nonpharmacological palliative intervention on dyspnea in
      patients with lung cancer. METHODS: This study used open, randomized, controlled,
      crossover trial design involved 21 participants. Diaphragmatic breathing
      technique was used in control arm. RESULTS: Wilcoxon test result showed that
      airflow stimulation significantly influenced dyspnea scale (P = 0.003) and
      respiratory rate (RR) (P = 0.008). Combination of airflow stimulation and
      diaphragmatic breathing can lower both dyspnea scale and RR significantly (P <
      0.0001). CONCLUSIONS: This combination can be applied on nonhypoxemic dyspneic
      lung cancer patients.

PMID- 28503651
TI  - Effect of Play-based Occupational Therapy on Symptoms of Hospitalized Children
      with Cancer: A Single-subject Study.
AB  - OBJECTIVE: Cancer is one of the four leading causes of death in children. Its
      courses of diagnosis and treatment can cause physiologic symptoms and
      psychological distress that secondarily affect children's quality of life and
      participation in daily activities. The aim of this study was to investigate the
      effect of play-based occupational therapy on pain, anxiety, and fatigue in
      hospitalized children with cancer who were receiving chemotherapy. METHODS: Two
      hospitalized children with acute lymphoblastic leukemia at least 4 months after
      diagnoses who received two courses of chemotherapy participated in this pilot
      study. Takata Play History and Iranian Children Participation Assessment Scale
      were used to develop intervention protocol. Nine, 30-45 min play-based
      occupational therapy sessions took place for each child. Children filled out the
      Faces Pain Scale, Visual Fatigue Scale, and Faces Anxiety Scale before and after
      each intervention session. RESULTS: Pain, anxiety, and fatigue levels decreased
      in both participants. Furthermore, the results showed a relationship between
      pain, anxiety, and fatigue variables in these children. CONCLUSIONS: Play-based
      occupational therapy can be effective in improving pain, anxiety, and fatigue
      levels in hospitalized children with cancer receiving chemotherapy.

PMID- 28503653
TI  - Editorial overview: Neuroscience of education.

PMID- 28503652
TI  - Experiences of Caregivers with Spouses Receiving Chemotherapy for Colorectal
      Cancer and their Expectations from Nursing Services.
AB  - OBJECTIVE: The purpose of this study was to reveal experiences of caregivers
      whose spouses were receiving chemotherapy for colorectal cancer and their
      expectations from nursing services. METHODS: This is a qualitative study. The
      caregivers were interviewed at their home. Sampling criteria were volunteering to
      participate in the study, being able to understand Turkish, not having speech or
      hearing problems and offering care to spouses with primary colorectal cancer. The
      interviews continued until concepts likely to be responses to research questions
      repeatedly appeared. Fourteen caregivers with spouses receiving chemotherapy for
      colorectal cancer comprised the study sample. Data were collected with a
      descriptive characteristics form and a semi-structured interview at in-depth
      interviews after making appointments with the caregivers on the phone. The steps
      followed in the content analysis were coding data, an organization of codes and
      themes, description of findings and evaluation of findings. RESULTS: Experiences
      of the caregivers whose spouses were receiving chemotherapy for colorectal cancer
      and their expectations from nursing services were found to comprise the following
      themes "Facing the Disease," "Difficulties Encountered," "Continuing to Live,"
      and "Provision of Health Care Services." CONCLUSIONS: The results of the study
      revealed that cancer and its treatment affected not only cancer patients but also
      their spouses offering care. Nurses giving care at oncology clinics, public
      health centers, and home can make care plans based on the four themes emerging in
      this study and can detect problems earlier and create appropriate solutions to
      them. They will contribute to the literature revealing needs of people offering
      care to oncology patients as well.

PMID- 28503654
TI  - Protective Processes Underlying the Links between Marital Quality and Physical
      Health.
AB  - Although the links between marital quality and physical health are now well
      established, the psychological processes through which marriage impacts health
      remain unclear. Additionally, prior research on the links between marriage and
      health has focused mainly on how negative aspects of relationships (e.g.,
      conflict, hostility) can be damaging to one's physical health. In this article,
      we describe the strength and strain model of marital quality and health, which
      provides a roadmap for studying protective factors underlying marriage-health
      links. We home in one relationship process-partner responsiveness-and one broad
      class of psychological mechanisms-affective processes-to illustrate core aspects
      of the model. Our review suggests that future research will profit from a greater
      integration of theory from the social psychology of close relationships into
      studies of relationships and health.

PMID- 28503655
TI  - Parenting and SES: relative values or enduring principles?
AB  - The quality of parenting is a complex and multiply determined construct that is
      strongly influenced by the larger ecological context in which it evolves. A
      substantial body of literature has documented associations between socioeconomic
      status (SES) and parenting but has been limited in its consideration of factors
      that may explain or moderate the nature of this relation. The socioeconomic
      conditions within which a family lives may powerfully influence parenting through
      its effects on parental mental health and via differential access to resources.
      Parents' childrearing knowledge and cultural values may also vary along a
      socioeconomic gradient, with downstream effects on parenting. Further, both
      socioeconomic factors and parenting can independently shape children's health and
      development. A more comprehensive understanding of linkages between SES and
      parenting may inform preventive intervention efforts to support families from
      disadvantaged environments.

PMID- 28503656
TI  - Communication Bridge: A pilot feasibility study of Internet-based speech-language
      therapy for individuals with progressive aphasia.
AB  - INTRODUCTION: Individuals with aphasia symptoms due to neurodegenerative dementia
      are under-referred for speech-language therapy (SLT) services. We sought to
      determine the feasibility of utilizing telepractice, via Internet video
      conferencing, to connect an individual with progressive aphasia due to dementia
      to a speech-language pathologist for treatment. METHODS: Participants received an
      Initial Evaluation, 8 person-centered Internet-based SLT sessions and two Post
      Therapy Evaluations. The feasibility of providing web-based SLT, strategies used
      and their compliance, functional gains and the duration of benefit were assessed.
      RESULTS: Thirty-four participants from 21 states and Canada were enrolled. Thirty
      one participants completed the 6-month Evaluation. Speech-language pathologist
      assessed and self-reported functional gains, as well as increased confidence in
      communication were documented at 2-months and maintained at 6-months post
      enrollment. DISCUSSION: Internet-based SLT using person-centered interventions
      provides a feasible model for delivering care to individuals with dementia and
      mild/moderate aphasia symptoms who have an engaged care-partner and prior
      familiarity with a computer.

PMID- 28503657
TI  - An amylin analog used as a challenge test for Alzheimer's disease.
AB  - INTRODUCTION: Preclinical studies demonstrate the potential of amylin in the
      diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for
      repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans.
      METHODS: We administered a single subcutaneous injection of 60 MUg of pramlintide
      to nondiabetic subjects under fasting conditions. RESULTS: None of the
      participants developed hypoglycemia after the injection of pramlintide. The
      pramlintide challenge induced a significant surge of amyloid-beta peptide and a
      decrease in total tau in the plasma of AD subjects but not in control
      participants. The pramlintide injection provoked an increase in interleukin 1
      receptor antagonist and a decrease in retinol-binding protein 4, which separates
      AD subjects from control subjects. DISCUSSION: Pramlintide use appeared to be
      safe in the absence of diabetes. The biomarker changes as a result of the
      pramlintide challenge, which distinguished AD from control subjects and mild
      cognitive impairment.

PMID- 28503658
TI  - Emerging Loop-Mediated Isothermal Amplification-Based Microchip and Microdevice
      Technologies for Nucleic Acid Detection.
AB  - Rapid, sensitive, and selective pathogen detection is of paramount importance in
      infectious disease diagnosis and treatment monitoring. Currently available
      diagnostic assays based on polymerase chain reaction (PCR) and enzyme-linked
      immunosorbent assay (ELISA) are time-consuming, complex, and relatively
      expensive, thus limiting their utility in resource-limited settings. Loop
      mediated isothermal amplification (LAMP) technique has been used extensively in
      the development of rapid and sensitive diagnostic assays for pathogen detection
      and nucleic acid analysis and hold great promise for revolutionizing point-of
      care molecular diagnostics. Here, we review novel LAMP-based lab-on-a-chip (LOC)
      diagnostic assays developed for pathogen detection over the past several years.
      We review various LOC platforms based on their design strategies for pathogen
      detection and discuss LAMP-based platforms still in development and already in
      the commercial pipeline. This review is intended as a guide to the use of LAMP
      techniques in LOC platforms for molecular diagnostics and genomic amplifications.

PMID- 28503660
TI  - Breast Cancer Downstaging Practices and Breast Health Messaging Preferences Among
      a Community Sample of Urban and Rural Ugandan Women.
AB  - PURPOSE: Among a community sample of Ugandan women, we provide information about
      breast cancer downstaging practices (breast self-examination, clinical breast
      examination [CBE]) and breast health messaging preferences across
      sociodemographic, health care access, and prior breast cancer exposure factors.
      METHODS: Convenience-based sampling was conducted to recruit Ugandan women age 25
      years and older to assess breast cancer downstaging practices as well as breast
      health messaging preferences to present early for a CBE in the theoretical
      scenario of self-detection of a palpable lump (breast health messaging
      preferences). RESULTS: The 401 Ugandan women who participated in this survey were
      mostly poor with less than a primary school education. Of these women, 27% had
      engaged in breast self-examination, and 15% had undergone a CBE. Greater breast
      cancer downstaging practices were associated with an urban location, higher
      education, having a health center as a regular source of care, and receiving
      breast cancer education (P < .05). Women indicated a greater breast health
      messaging preference from their provider (66%). This preference was associated
      with a rural location, having a health center as a regular source of care, and
      receiving breast cancer education (P < .05). CONCLUSION: Most Ugandan women do
      not participate in breast cancer downstaging practices despite receipt of breast
      cancer education. However, such education increases downstaging practices and
      preference for messaging from their providers. Therefore, efforts to downstage
      breast cancer in Uganda should simultaneously raise awareness in providers and
      support improved education efforts in the community.

PMID- 28503659
TI  - Structure and function of histone acetyltransferase MOF.
AB  - MOF was first identified in Drosophila melanogaster as an important component of
      the dosage compensation complex. As a member of MYST family of histone
      acetyltransferase, MOF specifically deposits the acetyl groups to histone H4
      lysine 16. Throughout evolution, MOF and its mammalian ortholog have retained
      highly conserved substrate specificity and similar enzymatic activities. MOF
      plays important roles in dosage compensation, ESC self-renewal, DNA damage and
      repair, cell survival, and gene expression regulation. Dysregulation of MOF has
      been implicated in tumor formation and progression of many types of human
      cancers. This review will discuss the structure and activity of mammalian hMOF as
      well as its function in H4K16 acetylation, DNA damage response, stem cell
      pluripotency, and carcinogenesis.

PMID- 28503662
TI  - Picoliter-volume inkjet printing into planar microdevice reservoirs for low
      waste, high-capacity drug loading.
AB  - Oral delivery of therapeutics is the preferred route for systemic drug
      administration due to ease of access and improved patient compliance. However,
      many therapeutics suffer from low oral bioavailability due to low pH and
      enzymatic conditions, poor cellular permeability, and low residence time.
      Microfabrication techniques have been used to create planar, asymmetric
      microdevices for oral drug delivery to address these limitations. The geometry of
      these microdevices facilitates prolonged drug exposure with unidirectional
      release of drug toward gastrointestinal epithelium. While these devices have
      significantly enhanced drug permeability in vitro and in vivo, loading drug into
      the micron-scale reservoirs of the devices in a low-waste, high-capacity manner
      remains challenging. Here, we use picoliter-volume inkjet printing to load
      topotecan and insulin into planar microdevices efficiently. Following a simple
      surface functionalization step, drug solution can be spotted into the microdevice
      reservoir. We show that relatively high capacities of both topotecan and insulin
      can be loaded into microdevices in a rapid, automated process with little to no
      drug waste.

PMID- 28503663
TI  - The Communication Play Protocol: Capturing Variations in Language Development.
AB  - The Communication Play Protocol (CPP) is a semi-naturalistic, lab-based
      observational procedure that showcases parent-child interactions. This article
      reflects on how the CPP has matured since we described it over 25 years ago in
      the May 1999 issue of Perspectives. We emphasize how the CPP has provided us with
      a stable frame to observe both typically developing children and children with
      developmental challenges including autism spectrum disorder as they communicate
      with caregivers in a range of contexts. We also describe three versions of the
      CPP that have been designed to address different research questions and several
      methods including engagement state coding and rating items that have been used to
      extract data from video records of the CPP. We conclude that the CPP can provide
      both researchers and clinicians with a valuable way to systematically capture
      variations in language development.

PMID- 28503661
TI  - In vitro Detection of Hypoxia using a Ratiometric Quantum Dot-based Oxygen
      Sensor.
AB  - A quantum-dot based ratiometric fluorescent oxygen probe for the detection of
      hypoxia in live cells is reported. The system is comprised of a water-soluble
      near-infrared emissive quantum dot conjugated to perylene dye. The response to
      the oxygen concentration is investigated using enzymatic oxygen scavenging in
      water, while in vitro studies were performed with HeLa cells incubated under
      varying O2 levels. In both cases a significant enhancement in dye/QD emission
      intensity ratio was observed in the deoxygenated environment, demonstrating the
      possible use of this probe for cancer research.

PMID- 28503665
TI  - Probabilistic modeling of bifurcations in single-cell gene expression data using
      a Bayesian mixture of factor analyzers.
AB  - Modeling bifurcations in single-cell transcriptomics data has become an
      increasingly popular field of research. Several methods have been proposed to
      infer bifurcation structure from such data, but all rely on heuristic non
      probabilistic inference. Here we propose the first generative, fully
      probabilistic model for such inference based on a Bayesian hierarchical mixture
      of factor analyzers. Our model exhibits competitive performance on large datasets
      despite implementing full Markov-Chain Monte Carlo sampling, and its unique
      hierarchical prior structure enables automatic determination of genes driving the
      bifurcation process. We additionally propose an Empirical-Bayes like extension
      that deals with the high levels of zero-inflation in single-cell RNA-seq data and
      quantify when such models are useful. We apply or model to both real and
      simulated single-cell gene expression data and compare the results to existing
      pseudotime methods. Finally, we discuss both the merits and weaknesses of such a
      unified, probabilistic approach in the context practical bioinformatics analyses.

PMID- 28503664
TI  - Fixing the stimulus-as-fixed-effect fallacy in task fMRI.
AB  - Most functional magnetic resonance imaging (fMRI) experiments record the brain's
      responses to samples of stimulus materials (e.g., faces or words). Yet the
      statistical modeling approaches used in fMRI research universally fail to model
      stimulus variability in a manner that affords population generalization, meaning
      that researchers' conclusions technically apply only to the precise stimuli used
      in each study, and cannot be generalized to new stimuli. A direct consequence of
      this stimulus-as-fixed-effect fallacy is that the majority of published fMRI
      studies have likely overstated the strength of the statistical evidence they
      report. Here we develop a Bayesian mixed model (the random stimulus model; RSM)
      that addresses this problem, and apply it to a range of fMRI datasets. Results
      demonstrate considerable inflation (50-200% in most of the studied datasets) of
      test statistics obtained from standard "summary statistics"-based approaches
      relative to the corresponding RSM models. We demonstrate how RSMs can be used to
      improve parameter estimates, properly control false positive rates, and test
      novel research hypotheses about stimulus-level variability in human brain
      responses.

PMID- 28503666
TI  - Robust long-read native DNA sequencing using the ONT CsgG Nanopore system.
AB  - Background: The ability to obtain long read lengths during DNA sequencing has
      several potentially important practical applications. Especially long read
      lengths have been reported using the Nanopore sequencing method, currently
      commercially available from Oxford Nanopore Technologies (ONT). However, early
      reports have demonstrated only limited levels of combined throughput and sequence
      accuracy. Recently, ONT released a new CsgG pore sequencing system as well as a
      250b/s translocation chemistry with potential for improvements. Methods: We made
      use of such components on ONTs miniature 'MinION' device and sequenced native
      genomic DNA obtained from the near haploid cancer cell line HAP1. Analysis of our
      data was performed utilising recently described computational tools tailored for
      nanopore/long-read sequencing outputs, and here we present our key findings.
      Results: From a single sequencing run, we obtained ~240,000 high-quality mapped
      reads, comprising a total of ~2.3 billion bases. A mean read length of 9.6kb and
      an N50 of ~17kb was achieved, while sequences mapped to reference with a mean
      identity of 85%. Notably, we obtained ~68X coverage of the mitochondrial genome
      and were able to achieve a mean consensus identity of 99.8% for sequenced mtDNA
      reads. Conclusions: With improved sequencing chemistries already released and
      higher-throughput instruments in the pipeline, this early study suggests that ONT
      CsgG-based sequencing may be a useful option for potential practical long-read
      applications.

PMID- 28503667
TI  - Neopeptide Analyser: A software tool for neopeptide discovery in proteomics data.
AB  - Experiments involving mass spectrometry (MS)-based proteomics are widely used for
      analyses of connective tissues. Common examples include the use of relative
      quantification to identify differentially expressed peptides and proteins in
      cartilage and tendon. We are working on characterising so-called 'neopeptides',
      i.e. peptides formed due to native cleavage of proteins, for example under
      pathological conditions. Unlike peptides typically quantified in MS workflows due
      to the in vitro use of an enzyme such as trypsin, a neopeptide has at least one
      terminus that was not due to the use of trypsin in the workflow. The
      identification of neopeptides within these datasets is important in understanding
      disease pathology, and the development of antibodies that could be utilised as
      diagnostic biomarkers for diseases, such as osteoarthritis, and targets for novel
      treatments. Our previously described neopeptide data analysis workflow was
      laborious and was not amenable to robust statistical analysis, which reduced
      confidence in the neopeptides identified. To overcome this, we developed
      'Neopeptide Analyser', a user friendly neopeptide analysis tool used in
      conjunction with label-free MS quantification tool Progenesis QIP for proteomics.
      Neopeptide Analyser filters data sourced from Progenesis QIP output to identify
      neopeptide sequences, as well as give the residues that are adjacent to the
      peptide in its corresponding protein sequence. It also produces normalised values
      for the neopeptide quantification values and uses these to perform statistical
      tests, which are also included in the output. Neopeptide Analyser is available as
      a Java application for Mac, Windows and Linux. The analysis features and ease of
      use encourages data exploration, which could aid the discovery of novel pathways
      in extracellular matrix degradation, the identification of potential biomarkers
      and as a tool to investigate matrix turnover. Neopeptide Analyser is available
      from https://github.com/PGB-LIV/neo-pep-tool/releases/.

PMID- 28503668
TI  - David Stafford-Clark (1916-1999): Seeing through a celebrity psychiatrist.
AB  - This article uses the mass-media career of the British psychiatrist David
      Stafford-Clark (1916-1999) as a case study in the exercise of cultural authority
      by celebrity medical professionals in post-war Britain. Stafford-Clark rose to
      prominence in the mass media, particularly through his presenting work on medical
      and related topics for BBC TV and Radio, and was in the vanguard of psychiatrists
      and physicians who eroded professional edicts on anonymity. At the height of his
      career, he traded upon his celebrity status, and consequent cultural authority,
      to deliver mass media sermons on a variety of social, cultural, and political
      topics. Stafford-Clark tried to preserve his sense of personal and intellectual
      integrity by clinging to a belief that his authority in the public sphere was
      ultimately to be vindicated by his literary, intellectual, and spiritual
      significance. But as his credibility dwindled, he came to distrust the cultural
      intermediaries, such as broadcasters and publishers, who had supported him.

PMID- 28503669
TI  - Dietary diversity and child malnutrition in Ghana.
AB  - The health of children in Ghana has improved in recent years. However, the
      current prevalence rates of malnutrition remain above internationally acceptable
      levels. This study, therefore, revisits the determinants of child health by using
      Ghana's Multiple Indicator Cluster Survey to investigate the effect of infant
      feeding practices on child health. We used the World Health Organization's Infant
      and Young Children Feeding guidelines to measure dietary quality. The econometric
      analyses show that dietary diversity may cause improvement in children's health
      in Ghana. This suggests that educational campaigns on proper infant feeding and
      complementary dieting could be an effective means of improving the health of
      children in Ghana.

PMID- 28503672
TI  - Quantum fluctuations beyond the Gutzwiller approximation.
AB  - We present a simple scheme to evaluate linear response functions including
      quantum fluctuation corrections on top of the Gutzwiller approximation. The
      method is derived for a generic multiband lattice Hamiltonian without any
      assumption about the dynamics of the variational correlation parameters that
      define the Gutzwiller wavefunction, and which thus behave as genuine dynamical
      degrees of freedom that add on those of the variational uncorrelated Slater
      determinant. We apply the method to the standard half-filled single-band Hubbard
      model. We are able to recover known results, but, as by-product, we also obtain
      few novel ones. In particular, we show that quantum fluctuations can reproduce
      almost quantitatively the behaviour of the uniform magnetic susceptibility
      uncovered by dynamical mean field theory, which, though enhanced by correlations,
      is found to be smooth across the paramagnetic Mott transition. By contrast, the
      simple Gutzwiller approximation predicts that susceptibility to diverge at the
      transition.

PMID- 28503670
TI  - Encoding of contextual fear memory requires de novo proteins in the prelimbic
      cortex.
AB  - BACKGROUND: Despite our understanding of the significance of the prefrontal
      cortex in the consolidation of long-term memories (LTM), its role in the encoding
      of LTM remains elusive. Here we investigated the role of new protein synthesis in
      the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory.
      METHODS: Because a change in the association of mRNAs to polyribosomes is an
      indicator of new protein synthesis, we assessed the changes in polyribosome
      associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the
      mouse. Differential gene expression in mPFC was identified by polyribosome
      profiling (n = 18). The role of new protein synthesis in mPFC was determined by
      focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex
      manipulation (n = 56) of Homer 3, a candidate identified from polyribosome
      profiling. RESULTS: We identified several mRNAs that are differentially and
      temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of
      protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex
      (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual
      fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours
      after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA
      enriched in polyribosomes following CFC, in the PL constrained encoding of
      contextual fear memory. CONCLUSIONS: Our studies identify several molecular
      substrates of new protein synthesis in the mPFC and establish that encoding of
      contextual fear memories require new protein synthesis in PL subregion of mPFC.

PMID- 28503671
TI  - HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.
AB  - BACKGROUND: We have previously reported that persons co-infected with HIV and
      hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected
      individuals who were approximately 10 years older. Insulin-like growth factor
      1(IGF-1) levels have long been known to decline with advancing age in humans and
      non-humans alike. We examined whether HIV infection affects the expected decline
      in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that
      alteration in IGF-1 decline contributes to the link between HIV, aging, and liver
      disease progression. METHODS: A total of 553 individuals with HCV infection were
      studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for
      whom more than 10 years of follow-up was available. Serum IGF-1 levels were
      determined by ELISA and evaluated according to baseline characteristics and over
      time by HIV status and liver disease progression. Linear regression with
      generalized estimating equations was used to determine whether IGF-1 decline over
      time was independently associated with liver disease progression. RESULTS:
      Baseline IGF-1 levels were strongly associated with age (P < 0.0001) but not with
      gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each
      year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in
      HIV/HCV co-infected individuals (P < 0.05). In a multivariable linear regression
      model, progression of liver fibrosis was associated with HIV infection and age,
      as well as with a slower rate of IGF-1 decline (P = 0.001); however, the rate of
      IGF-1 decline did not alter the strength of the associations between HIV, liver
      disease, and age. CONCLUSIONS: The normal decline in IGF-1 levels with age was
      attenuated in HIV/HCV co-infected individuals compared to those with HCV mono
      infection, and slower IGF-1 decline was independently associated with liver
      disease progression.

PMID- 28503673
TI  - Non-Fermi-liquid behavior in quantum impurity models with superconducting
      channels.
AB  - We study how the non-Fermi-liquid nature of the overscreened multi-channel Kondo
      impurity model affects the response to a BCS pairing term that, in the absence of
      the impurity, opens a gap Delta. We find that the low-energy spectrum in the
      limit Delta -> 0 actually does not correspond to the spectrum strictly at Delta =
      0. In particular, in the two-channel Kondo model the Delta -> 0 ground state is
      an orbitally degenerate spin-singlet, while it is an orbital singlet with a
      residual spin degeneracy at Delta = 0. In addition, there are fractionalized spin
      1/2 sub-gap excitations whose energy in units of Delta tends towards a finite and
      universal value when Delta -> 0; as if the universality of the anomalous power
      law exponents that characterise the overscreened Kondo effect turned into
      universal energy ratios when the scale invariance is broken by Delta ? 0. This
      intriguing phenomenon can be explained by the renormalisation flow towards the
      overscreened fixed point and the gap cutting off the orthogonality catastrophe
      singularities. We also find other non-Fermi liquid features at finite Delta: the
      local density of states lacks coherence peaks, the states in the continuum above
      the gap are unconventional, and the boundary entropy is a non-monotonic function
      of temperature. The persistent sub-gap excitations are characteristic of the non
      Fermi-liquid fixed-point of the model, and thus depend on the impurity spin and
      the number of screening channels.

PMID- 28503674
TI  - Identifying brain nociceptive information transmission in patients with chronic
      somatic pain.
AB  - INTRODUCTION: Recent advances regarding mechanisms of chronic pain emphasize the
      role of corticolimbic circuitry in predicting risk for chronic pain,
      independently from site of injury-related parameters. These results compel
      revisiting the role of peripheral nociceptive signaling in chronic pain. We
      address this issue by examining what brain circuitry transmit information
      regarding the intensity of chronic pain and how this information may be related
      to a common co-morbidity, depression. METHODS: Resting state functional MRI was
      used in a large group of chronic pain patients (n=40 chronic back pain, CBP, and
      n=44 osteoarthritis, OA patients), and in comparison to healthy subjects (n=88).
      We used a graph theoretical measure, degree count, to investigate voxel-wise
      information sharing/transmission in the brain. Degree count, a functional
      connectivity based measure, identifies the number of voxels functionally
      connected to every given voxel. Subdividing the chronic pain cohort into
      discovery, replication, and also for overall group we show that only degree
      counts of diencephalic voxels centered in the ventral lateral thalamus reflected
      intensity of chronic pain, independently of depression. RESULTS: Pain intensity
      was reliably associated with degree count of the thalamus, which was correlated
      negatively with components of the default mode network and positively with the
      periaqueductal grey (in contrast to healthy controls). Depression scores were not
      reliably associated with regional degree count. CONCLUSION: Collectively the
      results suggest that, across two types of chronic pain, nociceptive specific
      information is relayed through the spinothalamic pathway to the lateral thalamus,
      potentiated by pro-nociceptive descending modulation, and interrupting cortical
      cognitive processes.

PMID- 28503675
TI  - Costs of a Staff Communication Intervention to Reduce Dementia Behaviors in
      Nursing Home Care.
AB  - CONTEXT: Persons with Alzheimer's disease and other dementias experience
      behavioral symptoms that frequently result in nursing home (NH) placement.
      Managing behavioral symptoms in the NH increases staff time required to complete
      care, and adds to staff stress and turnover, with estimated cost increases of
      30%. The Changing Talk to Reduce Resistivenes to Dementia Care (CHAT) study found
      that an intervention that improved staff communication by reducing elderspeak led
      to reduced behavioral symptoms of dementia or resistiveness to care (RTC).
      OBJECTIVE: This analysis evaluates the cost-effectiveness of the CHAT
      intervention to reduce elderspeak communication by staff and RTC behaviors of NH
      residents with dementia. DESIGN: Costs to provide the intervention were
      determined in eleven NHs that participated in the CHAT study during 2011-2013
      using process-based costing. Each NH provided data on staff wages for the quarter
      before and for two quarters after the CHAT intervention. An incremental cost
      effectiveness analysis was completed. ANALYSIS: An average cost per participant
      was calculated based on the number and type of staff attending the CHAT training,
      plus materials and interventionist time. Regression estimates from the parent
      study then were applied to determine costs per unit reduction in staff elderspeak
      communication and resident RTC. RESULTS: A one percentage point reduction in
      elderspeak costs $6.75 per staff member with average baseline elderspeak usage.
      Assuming that each staff cares for 2 residents with RTC, a one percentage point
      reduction in RTC costs $4.31 per resident using average baseline RTC.
      CONCLUSIONS: Costs to reduce elderspeak and RTC depend on baseline levels of
      elderspeak and RTC, as well as the number of staff participating in CHAT training
      and numbers of residents with dementia-related behaviors. Overall, the 3-session
      CHAT training program is a cost-effective intervention for reducing RTC behaviors
      in dementia care.

PMID- 28503676
TI  - Learning Optimal Individualized Treatment Rules from Electronic Health Record
      Data.
AB  - Medical research is experiencing a paradigm shift from "one-size-fits-all"
      strategy to a precision medicine approach where the right therapy, for the right
      patient, and at the right time, will be prescribed. We propose a statistical
      method to estimate the optimal individualized treatment rules (ITRs) that are
      tailored according to subject-specific features using electronic health records
      (EHR) data. Our approach merges statistical modeling and medical domain knowledge
      with machine learning algorithms to assist personalized medical decision making
      using EHR. We transform the estimation of optimal ITR into a classification
      problem and account for the non-experimental features of the EHR data and
      confounding by clinical indication. We create a broad range of feature variables
      that reflect both patient health status and healthcare data collection process.
      Using EHR data collected at Columbia University clinical data warehouse, we
      construct a decision tree for choosing the best second line therapy for treating
      type 2 diabetes patients.

PMID- 28503677
TI  - Annotating Logical Forms for EHR Questions.
AB  - This paper discusses the creation of a semantically annotated corpus of questions
      about patient data in electronic health records (EHRs). The goal is to provide
      the training data necessary for semantic parsers to automatically convert EHR
      questions into a structured query. A layered annotation strategy is used which
      mirrors a typical natural language processing (NLP) pipeline. First, questions
      are syntactically analyzed to identify multi-part questions. Second, medical
      concepts are recognized and normalized to a clinical ontology. Finally, logical
      forms are created using a lambda calculus representation. We use a corpus of 446
      questions asking for patient-specific information. From these, 468 specific
      questions are found containing 259 unique medical concepts and requiring 53
      unique predicates to represent the logical forms. We further present detailed
      characteristics of the corpus, including inter-annotator agreement results, and
      describe the challenges automatic NLP systems will face on this task.

PMID- 28503678
TI  - Beyond Abandonment to Next Steps: Understanding and Designing for Life after
      Personal Informatics Tool Use.
AB  - Recent research examines how and why people abandon self-tracking tools. We
      extend this work with new insights drawn from people reflecting on their
      experiences after they stop tracking, examining how designs continue to influence
      people even after abandonment. We further contrast prior work considering
      abandonment of health and wellness tracking tools with an exploration of why
      people abandon financial and location tracking tools, and we connect our findings
      to models of personal informatics. Surveying 193 people and interviewing 12
      people, we identify six reasons why people stop tracking and five perspectives on
      life after tracking. We discuss these results and opportunities for design to
      consider life after self-tracking.

PMID- 28503680
TI  - Editorial: The dawn of adhesive dentistry.

PMID- 28503679
TI  - Crumbs: Lightweight Daily Food Challenges to Promote Engagement and Mindfulness.
AB  - Many people struggle with efforts to make healthy behavior changes, such as
      healthy eating. Several existing approaches promote healthy eating, but present
      high barriers and yield limited engagement. As a lightweight alternative approach
      to promoting mindful eating, we introduce and examine crumbs: daily food
      challenges completed by consuming one food that meets the challenge. We examine
      crumbs through developing and deploying the iPhone application Food4Thought. In a
      3-week field study with 61 participants, crumbs supported engagement and
      mindfulness while offering opportunities to learn about food. Our 2*2 study
      compared nutrition versus non-nutrition crumbs coupled with social versus non
      social features. Nutrition crumbs often felt more purposeful to participants, but
      non-nutrition crumbs increased mindfulness more than nutrition crumbs. Social
      features helped sustain engagement and were important for engagement with non
      nutrition crumbs. Social features also enabled learning about the variety of
      foods other people use to meet a challenge.

PMID- 28503682
TI  - Hydroboration of alkynes and nitriles using an alpha-diimine cobalt hydride
      catalyst.
AB  - Addition of NaEt3BH to (Ph2PPrDI)CoCl2 affords the corresponding monohydride,
      (Ph2PPrDI)CoH. X-ray diffraction and DFT calculations indicate that this compound
      possesses a radical monoanion alpha-DI chelate and a Co(ii) centre. Notably,
      (Ph2PPrDI)CoH catalyzes the hydroboration of alkynes and dihydroboration of
      nitriles under mild conditions.

PMID- 28503684
TI  - Phase transformations, anisotropic pyroelectric energy harvesting and
      electrocaloric properties of (Pb,La)(Zr,Sn,Ti)O3 single crystals.
AB  - (Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals with their chemical composition
      located at the tetragonal antiferroelectric region are grown via the flux method
      in a PbO-PbF2-B2O3 mixture. Segregation of the Ti4+ component in the as-grown
      crystals is observed due to the strong affinity between the oxygen anion and Ti4+
      ions. The critical electric field of the antiferroelectric to ferroelectric phase
      transition is determined to be about 0.5 kV mm-1. The electric field induced
      ferroelectric phase transforms back into the antiferroelectric phase at a
      depolarization temperature of 125  degrees C. Anisotropy of the harvested energy
      density and electrocaloric behaviors are achieved for the [100], [110] and [111]
      oriented PLZST crystals. Based on the thermodynamic theory approach, all the
      abovementioned behaviors originate from the anisotropic total entropy change.
      Enhanced electrocaloric strength (0.3 K mm kV-1) and the harvested energy density
      of 0.62 J cm-3 are obtained in the [111]-oriented PLZST crystals. Our results
      demonstrate the competence of PLZST single crystals for cooling devices and
      pyroelectric energy harvesting and provide new opportunities to improve energy
      harvesting density and electrocaloric properties via the anisotropic structural
      layout, which make the PLZST crystals attractive for solid state cooling devices
      and energy conversion technologies.

PMID- 28503683
TI  - Cellular evaluation of diselenonicotinamide (DSNA) as a radioprotector against
      cell death and DNA damage.
AB  - Diselenonicotinamide (DSNA), a synthetic organoselenium compound, was evaluated
      for its radioprotective effect in cellular models. A clonogenic assay in Chinese
      Hamster Ovary (CHO) cells and an apoptosis assay in murine splenic lymphocytes
      indicated that pre-treatment with DSNA at a concentration of 25 MUM significantly
      protected them from radiation-induced cell death. Upon irradiation (1-12 Gy),
      dose-response studies were carried out under similar treatment conditions, and
      its dose modification factor (DMF) was estimated to be 1.26. Furthermore, DSNA
      showed its radioprotective effect, even when administered after exposure to
      radiation. Mechanistic investigation revealed that DSNA increased the
      intracellular levels of GPx and GSH in irradiated cells. In line with this
      observation, the addition of a pharmacological inhibitor of GPx cycle, abrogated
      the activity of DSNA. The radioprotective effect of DSNA was also complemented by
      its ability to prevent radiation-induced DNA damage as monitored by micronucleus
      and gamma-H2AX assays. Furthermore, treatment with DSNA did not show much change
      in the expressions of Nrf2 dependent genes (gamma-GCL and HO-1), but the presence
      of a pharmacological inhibitor of Nrf2 abrogated the radioprotective activity of
      DSNA against cell death and DNA damage. Additionally, ATRA treatment also
      inhibited the DSNA-mediated up-regulation of a repair gene RAD51, suggesting
      possible involvement of basal Nrf2 in the anti-genotoxic effect of DSNA. In
      conclusion, the present study demonstrates radioprotection by a synthetic
      organoselenium compound containing nutritionally important moieties like selenium
      and nicotinamide.

PMID- 28503685
TI  - Intracellular-molecular changes in plasma-irradiated budding yeast cells studied
      using multiplex coherent anti-Stokes Raman scattering microscopy.
AB  - Interactions between non-equilibrium atmospheric-pressure plasma (NEAPP) and
      living cells were examined using multiplex coherent anti-Stokes Raman scattering
      (CARS) microscopy. Our multiplex CARS analyses revealed that NEAPP irradiation
      generates short-lived radicals that induce a decrease in the mitochondrial
      activity of budding yeast cells.

PMID- 28503686
TI  - Mesoporous nanocarriers with a stimulus-responsive cyclodextrin gatekeeper for
      targeting tumor hypoxia.
AB  - Tissue hypoxia developed in most malignant tumors makes a significant difference
      to normal tissues in the reduction potential and the activity of various
      bioreductive enzymes. Given the superior enzymatic activity of NAD(P)H:quinone
      oxidoreductase 1 (NQO1, a cytosolic reductase up-regulated in many human cancers)
      in hypoxia relative to that in normoxia, NQO1 has great potential for targeting
      hypoxic tumor cells. In the present report, the core concept of hypoxic NQO1
      responsive mesoporous silica nanoparticles (MSNs) is based on the reasoning that
      the superior enzymatic activity of NQO1 within hypoxic cancer cells can be
      utilized as a key stimulus for the selective cleavage of an azobenzene stalk
      triggering the on-off gatekeeping for controlled release of guest drugs. We
      corroborate that the NQO1 specifically triggers to release the entrapped drug in
      the nanochannel of MSNs by reductive cleavage of the azobenzene linker only under
      hypoxic conditions in a controlled manner not only in vitro but also in vivo.
      Therefore, our results indicate that Si-Azo-CD-PEG could be utilized as a hypoxic
      cancer-targeting drug delivery carrier, and further suggest that the azobenzene
      linker could generally be useful for the construction of hypoxic NQO1-responsive
      nanomaterials.

PMID- 28503687
TI  - Adapting BODIPYs to singlet oxygen production on silica nanoparticles.
AB  - A modified Stober method is used to synthesize spherical core-shell silica
      nanoparticles (NPs) with an external surface functionalized by amino groups and
      with an average size around 50 nm. Fluorescent dyes and photosensitizers of
      singlet oxygen were fixed, either separately or conjointly, respectively in the
      core or in the shell. Rhodamines were encapsulated in the core with relatively
      high fluorescence quantum yields (Phifl >= 0.3), allowing fluorescence tracking
      of the particles. Various photosensitizers of singlet oxygen (PS) were covalenty
      coupled to the shell, allowing singlet oxygen production. The stability of NP
      suspensions strongly deteriorated upon grafting the PS, affecting their apparent
      singlet oxygen quantum yields. Agglomeration of NPs depends both on the type and
      on the amount of grafted photosensitizer. New, lab-made, halogenated 4,4-difluoro
      4-bora-3a,4a-diaza-s-indacenes (BODIPY) grafted to the NPs achieved higher
      singlet oxygen quantum yields (PhiDelta ~ 0.35-0.40) than Rose Bengal (RB)
      grafted NPs (PhiDelta ~ 0.10-0.27). Finally, we combined both fluorescence and PS
      functions in the same NP, namely a rhodamine in the silica core and a BODIPY or
      RB grafted in the shell, achieving the performance Phifl ~ 0.10-0.20, PhiDelta ~
      0.16-0.25 with a single excitation wavelength. Thus, proper choice of the dyes,
      of their concentrations inside and on the NPs and the grafting method enables
      fine-tuning of singlet oxygen production and fluorescence emission.

PMID- 28503688
TI  - Intermolecular cascade annulations of N-(arylsulfonyl)acrylamides with dual
      C(sp3)-H bonds: divergent access to indanes and pyrrolidin-2-ones.
AB  - A new divergent intermolecular cascade annulation reaction of N
      (arylsulfonyl)acrylamides with dual alkyl C(sp3)-H bonds for producing two types
      of five-membered rings, indanes and pyrrolidin-2-ones, is described. By using
      cycloalkanes and common alkanes as a one-carbon unit, an intermolecular [4+1]
      cascade carboannulation of N-(arylsulfonyl)acrylamides was achieved via a
      sequence of three C-H bond functionalization/aryl migration/desulfonylation that
      enables the formation of three C-C bonds and one N-H bond. When the one-carbon
      unit was changed to cycloalkyl ethers, the alternative intermolecular [4+1]
      cascade heteroannulation reaction occurred and allowed the construction of two C
      C bonds and one C-N bond through dual C-H bond functionalization, aryl migration
      and desulfonylation cascades.

PMID- 28503689
TI  - Effects of elemene on inhibiting proliferation of vascular smooth muscle cells
      and promoting reendothelialization at the stent implantation site.
AB  - Anticancer drugs are commonly used as inhibitors of vascular smooth muscle cell
      (VSMC) proliferation in clinical treatments. This study aims to investigate how
      elemene affects the proliferation of VSMCs, the restenosis, and the
      reendothelialization after implanting the elemene-coated stents. VSMCs derived
      from rat aorta were used to test the cell proliferation, cell cycle, migration,
      apoptosis, cytoskeletal protein F-actin, intracellular Ca2+, IncRNA chip and gene
      expression of PCNA, P53, and Cx43 when cultured with elemene. It was found that
      elemene can inhibit proliferation, induce apoptosis and block the connections
      between VSMCs in a dose-dependent manner. IncRNA chip analysis has revealed that
      there was a significant difference in the expression of 1417 genes and 34
      signaling pathways. Elemene liposome membranes prepared by electrostatic spray
      could also inhibit the proliferation of VSMCs. In addition, after implanting the
      elemene-coated stent into a rabbit iliac artery for 12 weeks, the surface of
      elemene-coated stents was fully covered with a layer of neointima and a few
      platelets. However, a large number of platelets aggregated and attached on the
      uncoated stents (control samples). In conclusion, elemene could inhibit VSMC
      proliferation in vitro, which involved the regulation of various signal
      transduction pathways, and elemene-coated stents could promote endothelialization
      after stent implantation. Thus, elemene has great potential for the clinical
      treatment of restenosis and reendothelialization.

PMID- 28503690
TI  - Ionic liquid/H2O-mediated synthesis of mesoporous organic polymers and their
      application in methylation of amines.
AB  - Mesoporous Troger's base-functionalized polymers (Meso-TBPs) were prepared using
      a sulfonic acid group functionalized ionic liquid/H2O system, with surface areas
      up to 431 m2 g-1 and pore sizes of 3-15 nm. Ir(ii) coordinated Meso-TBPs
      exhibited extraordinary catalytic performance in the N-methylation of amines
      using methanol.

PMID- 28503691
TI  - A rapidly-prototyped microfluidic device for size-based nucleic acid
      fractionation using isotachophoresis.
AB  - We present a novel microfluidic device for size-based nucleic acid (NA)
      fractionation using isotachophoresis (ITP) and an ionic spacer. Our rapid
      prototyped laser-cut plastic device has easily modifiable channel dimensions, can
      process up to 10 MUL of sample, and contains an in-line extraction reservoir for
      minimally-disruptive manual collection of size-fractionated NAs. We designed
      custom buffering reservoirs using 1 mL pipette tips to provide high buffering
      capacity and prevent bubbles from entering the microfluidic channels. We
      demonstrated the utility of the device by implementing a proof-of-concept assay
      in which NAs were preconcentrated (via ITP) and then segregated by size (using
      the ionic spacer and sieving matrix) to generate two separate fractions, the
      first comprised of small (<50 nt) NA, and the second comprised of NAs of all
      sizes. Through this approach, we demonstrated size-based fractionation of both
      DNA and RNA samples (a mixture of synthetic ssDNA molecules, and a commercially
      available RNA molecular weight standard, respectively). Our results indicate that
      this simple, rapid (<=10 min), and label-free approach is a promising and cost
      effective alternative to the commercially-available size-selection kits currently
      on the market. We discuss the design and features of the device, as well as
      challenges which must be met in the future in order to further improve its
      performance and utility.

PMID- 28503692
TI  - Time-resolved measurements of product formation in the low-temperature (550-675
      K) oxidation of neopentane: a probe to investigate chain-branching mechanism.
AB  - Product formation, in particular ketohydroperoxide formation and decomposition,
      were investigated in time-resolved, Cl-atom initiated neopentane oxidation
      experiments in the temperature range 550-675 K using a photoionization time-of
      flight mass spectrometer. Ionization light was provided either by Advanced Light
      Source tunable synchrotron radiation or ~10.2 eV fixed energy radiation from a H2
      discharge lamp. Experiments were performed both at 1-2 atm pressure using a high
      pressure reactor and also at ~9 Torr pressure employing a low-pressure reactor
      for comparison. Because of the highly symmetric structure of neopentane,
      ketohydroperoxide signal can be attributed to a 3-hydroperoxy-2,2
      dimethylpropanal isomer, i.e. from a gamma-ketohydroperoxide (gamma-KHP). The
      photoionization spectra of the gamma-KHP measured at low- and high pressures and
      varying oxygen concentrations agree well with each other, further supporting they
      originate from the single isomer. Measurements performed in this work also
      suggest that the "Korcek" mechanism may play an important role in the
      decomposition of 3-hydroperoxy-2,2-dimethylpropanal, especially at lower
      temperatures. However, at higher temperatures where gamma-KHP decomposition to
      hydroxyl radical and oxy-radical dominates, oxidation of the oxy-radical yields a
      new important channel leading to acetone, carbon monoxide, and OH radical.
      Starting from the initial neopentyl + O2 reaction, this channel releases
      altogether three OH radicals. A strongly temperature-dependent reaction product
      is observed at m/z = 100, likely attributable to 2,2-dimethylpropanedial.

PMID- 28503693
TI  - Exploiting the unusual effects of fluorine in methodology.
AB  - Fluorination of organic molecules significantly impacts the basic physicochemical
      properties of small and large biologically active molecules, agrichemicals, and
      materials. Thus, the development of synthetic reactions to access these
      substructures is important for many applied fields of chemistry. However, these
      fluorine-induced perturbations of chemical properties can inhibit standard
      chemical transformations, which provides unique challenges for synthetic organic
      chemists. In addition, the physicochemical properties imparted by fluorinated
      substituents can enable distinct reactivity patterns relative to non-fluorinated
      substrates, thus making synthetic organofluorine chemistry a fertile ground for
      developing new, exciting transformations. In this feature article, we detail our
      experiences in methodology, wherein fluorinated substrates have enabled unique
      reactivity patterns relative to non-fluorous substrates. Specifically, we
      highlight the non-standard chemo- and regio-selectivities imparted by fluorinated
      substrates on Pd-catalyzed coupling reactions, nucleophilic addition reactions of
      olefins, and Cu-catalyzed decarboxylative fluoroalkylation reactions.

PMID- 28503694
TI  - Detection of early osteogenic commitment in primary cells using Raman
      spectroscopy.
AB  - Major challenges in the development of novel implant surfaces for artificial
      joints include osteoblast heterogeneity and the lack of a simple and sensitive in
      vitro assay to measure early osteogenic responses. Raman spectroscopy is a label
      free, non-invasive and non-destructive vibrational fingerprinting optical
      technique that is increasingly being applied to detect biochemical changes in
      cells. In this study Raman spectroscopy has been used to obtain bone cell
      specific spectral signatures and to identify any changes therein during
      osteoblast commitment and differentiation of primary cells in culture. Murine
      calvarial osteoblasts (COBs) were extracted and cultured and studied by Raman
      spectroscopy over a 14 day culture period. Distinct osteogenic Raman spectra were
      identified after 3 days of culture with strong bands detected for mineral:
      phosphate nu3 (1030 cm-1) and B-type carbonate (1072 cm-1), DNA (782 cm-1) and
      collagen matrix (CH2 deformation at 1450 cm-1) and weaker phosphate bands (948
      and 970 cm-1). Early changes were detected by Raman spectroscopy compared to a
      standard enzymatic alkaline phosphatase (ALP) assay and gene expression analyses
      over this period. Proliferation of COBs was confirmed by fluorescence intensity
      measurements using the Picogreen dsDNA reagent. Changes in ALP levels were
      evident only after 14 days of culture and mRNA expression levels for ALP, Col1a1
      and Sclerostin remained constant during the culture period. Sirius red staining
      for collagen deposition also revealed little change until day 14. In contrast
      Raman spectroscopy revealed the presence of amorphous calcium phosphate (945-952
      cm-1) and carbonated apatite (957-962 cm-1) after only 3 days in culture and
      octacalcium phosphate (970 cm-1) considered a transient mineral phase, was
      detected after 5 days of COBs culture. PCA analysis confirmed clear separation
      between time-points. This study highlights the potential of Raman spectroscopy to
      be utilised for the early and specific detection of proliferation and
      differentiation changes in primary cultures of bone cells.

PMID- 28503695
TI  - Cp*CoIII-catalyzed directed C-H trifluoromethylthiolation of 2-phenylpyridines
      and 6-arylpurines.
AB  - Cp*CoIII-catalyzed directed C-H trifluoromethylthiolation using N
      trifluoromethylthiodibenzenesulfonimide as an electrophilic SCF3 source is
      described. 6-Arylpurines, an important structural motif in medicinal chemistry,
      and 2-phenylpyridines selectively afforded mono-trifluoromethylthiolated products
      in moderate to good yields using an inexpensive first-row transition metal
      catalyst.

PMID- 28503697
TI  - Low-temperature-selective luminescent mechanochromism of a thienyl gold
      isocyanide complex.
AB  - The low-temperature-selective mechanochromism of a thienyl gold(i) isocyanide
      complex is reported. The as-prepared powder of this complex did not show any
      luminescent color changes upon grinding at room temperature. When cooled below 
      50  degrees C, the powder showed a blue emission in the absence of a phase
      transition. Upon grinding this powder below -50  degrees C, a green emission was
      observed, which indicates notable mechanochromism that only occurs at low
      temperature.

PMID- 28503696
TI  - Ion-induced molecular growth in clusters of small hydrocarbon chains.
AB  - We report on studies of collisions between 3 keV Ar+ projectile ions and neutral
      targets of isolated 1,3-butadiene (C4H6) molecules and cold, loosely bound
      clusters of these molecules. We identify molecular growth processes within the
      molecular clusters that appears to be driven by knockout processes and that could
      result in the formation of (aromatic) ring structures. These types of reactions
      are not unique to specific projectile ions and target molecules, but will occur
      whenever atoms or ions with suitable masses and kinetic energies collide with
      aggregates of matter, such as carbonaceous grains in the interstellar medium or
      aerosol nanoparticles in the atmosphere.

PMID- 28503698
TI  - Breast reconstruction rate and profile in a Singapore patient population: a
      National University Hospital experience.
AB  - INTRODUCTION: Breast reconstruction is an integral part of breast cancer
      management with the aim of restoring a breast to its natural form. There is
      increasing awareness among women that it is a safe procedure and its benefits
      extend beyond aesthetics. Our aim was to establish the rate of breast
      reconstruction and provide an overview of the patients who underwent breast
      reconstruction at National University Hospital (NUH), Singapore. METHODS: We
      evaluated factors that impact a patient's decision to proceed with breast
      reconstruction, such as ethnicity, age, time and type of implant. We
      retrospectively reviewed the medical records of women who had breast cancer and
      underwent breast surgery at NUH between 2001 and 2010. RESULTS: The breast
      reconstruction rate in this study was 24.3%. There were 241 patients who
      underwent breast reconstruction surgeries (including delayed and immediate
      procedures) among 993 patients for whom mastectomies were done for breast cancer.
      Chinese patients were the largest ethnic group who underwent breast
      reconstruction after mastectomy (74.3%). Within a single ethnic patient group,
      Malay women had the largest proportion of women undergoing breast reconstruction
      (60.0%). The youngest woman in whom cancer was detected in our study was aged 20
      years. Malay women showed the greatest preference for autologous tissue breast
      reconstruction (92.3%). The median age at cancer diagnosis of our cohort was 46
      years. CONCLUSION: We noted increases in the age of patients undergoing breast
      reconstruction and the proportion of breast reconstruction cases over the ten
      year study period.

PMID- 28503699
TI  - Eating psychopathology and psychosocial impairment in patients treated at a
      Singapore eating disorders treatment programme.
AB  - INTRODUCTION: There is limited data on the psychopathology of eating disorders in
      Singapore. This study: (a) described levels of eating psychopathology and
      psychosocial impairment among individuals diagnosed with eating disorders at our
      hospital; and (b) compared the related psychopathology of these patients.
      METHODS: Between 1 August 2010 and 31 July 2012, 257 individuals who met the
      diagnostic criteria for eating disorders completed the Eating Disorder
      Examination Questionnaire (EDE-Q) and Clinical Impairment Assessment
      questionnaire (CIA). RESULTS: A majority of participants were women and of
      Chinese ethnicity. Diagnoses included anorexia nervosa (AN; 41.6%), bulimia
      nervosa (BN; 29.6%) and eating disorder not otherwise specified (EDNOS; 28.8%).
      Mean age at presentation was 20.52 +/- 7.14 years and mean body mass index was
      17.84 +/- 4.18 kg/m2. Individuals with AN were significantly younger at
      presentation and had shorter duration of untreated illness compared to those with
      BN and EDNOS. There were no significant differences in the CIA scores of the
      diagnostic groups. Participants with BN scored higher in all subscales of the EDE
      Q than those with AN and EDNOS. Our sample scored lower in most subscales of EDE
      Q when compared to treatment centres in Sweden, Australia and the United States.
      CONCLUSION: Our clinical sample reported lower scores of psychopathology compared
      to overseas centres. This could be attributed to the higher percentages of BN and
      EDNOS diagnosed in overseas populations. Individuals with AN showed higher levels
      of psychopathology in our study compared to patients from the United States.

PMID- 28503700
TI  - Venous ultrasonography findings and clinical correlations in 104 Thai patients
      with chronic venous insufficiency of the legs.
AB  - INTRODUCTION: The pattern of venous reflux in Thai patients with chronic venous
      insufficiency (CVI) was studied in correlation with clinical manifestations.
      METHODS: Ultrasonography findings and clinical data were prospectively collected
      and retrospectively reviewed. RESULTS: CVI was found in 104 legs of 79 patients
      (mean age 59.8 +/- 12.5 years; C4: 24.1%, C5: 8.9%, C6: 67.1%). 6.7% of the legs
      had a history of deep vein thrombosis (DVT). The prevalence of superficial vein
      reflux (SVR), deep vein reflux (DVR), and combined SVR and DVR in 90 legs without
      previous venous surgery was 82.2%, 63.3% and 57.8%, respectively. In legs with
      SVR, the prevalence of great saphenous vein reflux (GSVR), small saphenous vein
      reflux (SSVR), and combined GSVR and SSVR was 91.9%, 33.8% and 25.7%,
      respectively. 77.0% of SVR involved the calf segment. For medial ulceration,
      79.6% had GSVR and 35.2% had SSVR. For lateral ulceration, 46.7% had SSVR and
      33.3% had isolated GSVR. Pulsatile venous signal was found in 3.3% of legs. In 17
      legs with ulceration after previous surgical treatment, calf vein reflux
      (residual calf great saphenous vein or small saphenous vein) was found in 13
      (76.5%) legs. CONCLUSION: Calf vein reflux plays an important role in CVI and in
      patients with recurrent ulceration after previous superficial venous surgery.
      Although GSVR was present in most patients with CVI in the legs, SSVR may present
      in one-third of patients, especially those with lateral ulceration. The high
      prevalence of DVR in the absence of DVT and the presence of a pulsatile venous
      signal in some patients highlight the incomplete understanding of CVI aetiology.

PMID- 28503701
TI  - Incorporating threat in hotspots and coldspots of biodiversity and ecosystem
      services.
AB  - Spatial prioritization could help target conservation actions directed to
      maintain both biodiversity and ecosystem services. We delineate hotspots and
      coldspots of two biodiversity conservation features and five regulating and
      cultural services by incorporating an indicator of 'threat', i.e. timber harvest
      profitability for forest areas in Telemark (Norway). We found hotspots, where
      high values of biodiversity, ecosystem services and threat coincide, ranging from
      0.1 to 7.1% of the area, depending on varying threshold levels. Targeting of
      these areas for conservation follows reactive conservation approaches. In
      coldspots, high biodiversity and ecosystem service values coincide with low
      levels of threat, and cover 0.1-3.4% of the forest area. These areas might serve
      proactive conservation approaches at lower opportunity cost (foregone timber
      harvest profits). We conclude that a combination of indicators of biodiversity,
      ecosystem services and potential threat is an appropriate approach for spatial
      prioritization of proactive and reactive conservation strategies.

PMID- 28503703
TI  - Abnormal vestibular-evoked myogenic potentials as an isolated finding of probable
      transient labyrinthine ischemia.

PMID- 28503702
TI  - Postmortem diagnosis of hyponatremia: case report and literature review.
AB  - Hyponatremia is defined as a plasma sodium concentration less than 135 or 130
      mEq/L (or mmol/L) and may be responsible for life threatening symptoms that can
      be observed in a variety of medical conditions. Cases of fatal hyponatremia have
      been reported in both clinical and forensic literature in situations of water
      intoxication due to psychogenic polydipsia, amphetamine derivative drug intake,
      high-endurance exercise, iatrogenic causes, and exceptional cases of child abuse
      by forced water intoxication. Vitreous sodium levels have been determined to be
      relatively stable during the early postmortem period and similar to levels found
      in normal serum of living subjects. Nevertheless, there are relatively few cases
      of fatal hyponatremia described in literature that underwent exhaustive
      postmortem biochemical investigations. A case of fatal water intoxication in a
      psychiatric patient who underwent medicolegal investigations, including
      postmortem biochemistry, was chosen as a starting point to a literature review of
      deaths by hyponatremia that may be encountered in the forensic setting.

PMID- 28503704
TI  - Use of EEG in critically ill children and neonates in the United States of
      America.
AB  - The objective of the study was to estimate the proportion of patients who receive
      an electroencephalogram (EEG) among five common indications for EEG monitoring in
      the intensive care unit: traumatic brain injury (TBI), extracorporeal membrane
      oxygenation (ECMO), cardiac arrest, cardiac surgery and hypoxic-ischemic
      encephalopathy (HIE). We performed a retrospective cross-sectional descriptive
      study utilizing the Kids' Inpatient Database (KID) for the years 2010-2012. The
      KID is the largest pediatric inpatient database in the USA and it is based on
      discharge reports created by hospitals for billing purposes. We evaluated the use
      of electroencephalogram (EEG) or video-electroencephalogram in critically ill
      children who were mechanically ventilated. The KID database had a population of
      approximately 6,000,000 pediatric admissions. Among 22,127 admissions of
      critically ill children who had mechanical ventilation, 1504 (6.8%) admissions
      had ECMO, 9201 (41.6%) TBI, 4068 (18.4%) HIE, 2774 (12.5%) cardiac arrest, and
      4580 (20.7%) cardiac surgery. All five conditions had a higher proportion of
      males, with the highest (69.8%) in the TBI group. The mortality rates ranged from
      7.02 to 39.9% (lowest in cardiac surgery and highest in ECMO). The estimated use
      of EEG was 1.6% in cardiac surgery, 4.1% in TBI, 7.2% in ECMO, 8.2% in cardiac
      arrest, and 12.1% in HIE, with an overall use of 5.8%. Among common indications
      for EEG monitoring in critically ill children and neonates, the estimated
      proportion of patients actually having an EEG is low.

PMID- 28503706
TI  - An eye-tracker controlled cognitive battery: overcoming verbal-motor limitations
      in ALS.
AB  - We assessed language, attention, executive, and social cognition abilities in a
      sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a
      recently developed cognitive battery based on oculomotor control with eye
      tracking (ET) technology. Twenty-one ALS patients and 21 age- and education
      matched healthy subjects underwent the ET-based cognitive assessment, together
      with the standard cognitive screening tools [Frontal Assessment Battery (FAB);
      Montreal Cognitive Assessment (MoCA); and Digit Sequencing Task]. Psychological
      measures of anxiety (State-Trait Anxiety Inventory-Y) and depression (Beck
      Depression Inventory) were also collected, and an ET usability questionnaire was
      administered. For patients, clinical and respiratory examinations were also
      performed, together with behavioural assessment (Frontal Behavioural Inventory).
      The developed battery discriminated among patients and controls with regard to
      measures of verbal fluency, frontal abilities, and social cognition. Measures of
      diagnostic utility confirmed a higher diagnostic accuracy of such ET-based tests
      with respect to FAB; similar diagnostic accuracy emerged when comparing them to
      the other standard cognitive tools (MoCA, WM). Usability ratings about the ET
      tests were comparable among the two groups. The ET-based neuropsychological
      battery demonstrated good levels of diagnostic accuracy and usability in a
      clinical population of non-demented ALS patients, compared to matched healthy
      controls. Future studies will be aimed at further investigate validity and
      usability components by recruiting larger sample of patients, both in moderate-to
      severe stages of the disease and affected by more severe cognitive impairment.

PMID- 28503705
TI  - Muscle MRI in neutral lipid storage disease (NLSD).
AB  - Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid
      metabolism resulting in lipid droplets accumulation in different tissues.
      Skeletal muscle could be affected in both two different form of disease: NLSD
      with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle
      imaging data of 12 patients from the Italian Network for NLSD: ten patients
      presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus,
      semimembranosus, soleus and gastrocnemius medialis in the lower limbs and
      infraspinatus in the upper limbs were the most affected muscles. Gracilis,
      sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid
      were spared. Muscle involvement was not homogenous and characteristic "patchy"
      replacement was observed in at least one muscle in all the patients. Half of the
      patients showed one or more STIR positive muscles. In both NLSD-I cases muscle
      involvement was not observed by T1-TSE sequences, but one of them showed positive
      STIR images in more than one muscle in the leg. Our data provides evidence that
      muscle imaging can identify characteristic alterations in NLSD-M, characterized
      by a specific pattern of muscle involvement with "patchy" areas of fatty
      replacement. Larger cohorts are needed to assess if a distinct pattern of muscle
      involvement exists also for NLSD-I.

PMID- 28503707
TI  - The value of ultrasound in diagnosing extracranial large-vessel vasculitis
      compared to FDG-PET/CT: A retrospective study.
AB  - Large-vessel vasculitis (LVV) is a group of diseases mainly comprised of giant
      cell arteritis (GCA), Takayasu arteritis, and a series of rare diseases like
      Behcet's disease, IgG4-related disease, infectious aortitis, and other unfrequent
      entities. Besides clinical and laboratory features, Doppler sonography (DS) can
      assist in establishing the diagnosis. Its diagnostic sensitivity has been
      evaluated in various studies, most of them, however, in temporal arteritis (TA)
      respectively in LVV with involvement of the temporal artery. Little is known in
      extracranial LVV. We retrospectively evaluated the diagnostic accuracy of DS in
      30 patients with extracranial, non-temporal LVV using the highly sensitive PET/CT
      as method of reference in comparison to 20 controls who were found to have no
      LVV. We investigated ten arterial sites and documented the presence of the
      sonographic halo sign. Sensitivities of DS for LVV were highest in the subclavian
      and axillary arteries (71.4%/72.2%) and low in the abdominal aorta (26.1%) and
      the common femoral artery (16.7%). DS detected 24 out of 30 cases of LVV (overall
      sensitivity 80.0%). The LVV cases where DS was completely negative did not
      significantly differ in leukocyte count, C-reactive protein, or erythrocyte
      sedimentation rate from LVV cases with positive DS. DS is a potent method in
      diagnosing extracranial LVV especially in the axillary and the subclavian
      arteries. Aortic, intraabdominal, and lower extremity artery manifestations,
      however, are often missed by DS. A second imaging modality (e.g., PET/CT) is
      therefore required.

PMID- 28503709
TI  - Morphological and molecular characterization of Sarcocystis arctica-like
      sarcocysts from the Arctic fox (Vulpes lagopus) from Alaska, USA.
AB  - The muscles of herbivores commonly harbor sarcocysts of parasites belonging to
      species in the genus Sarcocystis, but such muscle parasites are rare in
      carnivores. Here, we report Sarcocystis arctica-like sarcocysts in muscles of
      Arctic foxes (Vulpes lagopus) from Alaska, USA, for the first time. The tongues
      of 56 foxes were examined for Sarcocystis infection using several methods.
      Sarcocystis bradyzoites were detected in pepsin digests of 13 (23.2%), and
      sarcocysts were found in histological sections stained with hematoxylin and eosin
      (HE) of 9 (16.0%). By light microscopy, sarcocysts were up to 4 mm long and up to
      245 MUm wide. In HE-stained sections, the sarcocyst wall appeared smooth and up
      to 1.5 MUm thick without visible protrusions. By transmission electron
      microscopy, the sarcocyst wall had a wavy parasitophorous vacuolar membrane (pvm)
      folded as pleomorphic villar protrusions (vp), sometimes with anastomoses of
      villar tips. The vp and the ground substance (gs) layer were smooth and without
      microtubules. The gs was up to 2.0 MUm thick. The total width of the wall
      including vp and the gs was up to 4.0 MUm. The vp were up to 3.0 MUm long and
      most closely resembled "type 9c." All sarcocysts were mature and contained
      numerous 8.1 * 2.1 MUm sized bradyzoites. Molecular characterization (at 18S
      rDNA, 28S rDNA, ITS-1, and cox1) showed the highest affinity for S. arctica of
      the Arctic fox (V. lagopus) from Norway. In the present investigation, we provide
      evidence that sarcocysts are common in tongues of Alaskan Arctic foxes suggesting
      that these carnivores are serving as intermediate hosts, and we also provide
      ultrastructure of S. arctica from the Arctic fox for the first time.

PMID- 28503710
TI  - Characterization of a new multifunctional beta-glucosidase from Musca domestica.
AB  - OBJECTIVE: To engineer Pichia pastoris for heterologous production of cellulase
      from Musca domestica and explore its potential for industrial applications.
      RESULTS: A new beta-glucosidase gene (bg), encoding 562 amino acids, was cloned
      from M. domestica by using rapid amplification of cDNA ends. The gene bg was
      linked to pPICZalphaA and expressed in P. pastoris with a yield of 500 mg l-1.
      The enzyme has the maximum activity with 27.6 U mg-1 towards cellulose. The beta
      glucosidase has stable activity from 20 to 70  degrees C and can tolerate one
      mole glucose. It has the maximum activities for salicin (25.9 +/- 1.8 U mg-1),
      cellobiose (40.1 +/- 2.3 U mg-1) and cellulose (27.6 +/- 3.5 U mg-1). The wide
      range substrate activities of the beta-glucosidase were further verified by
      matrix-assisted laser desorption/ionization mass spectra. Structural analysis
      shows that the beta-glucosidase belongs to glycoside hydrolase family Iota and
      possesses O-glycosylation sites. CONCLUSIONS: Thus, a multifunctional beta
      glucosidase was expressed from M. domestica and provides a potential tool for
      industrial application of cellulose.

PMID- 28503712
TI  - Dupilumab Improves General Health-Related Quality-of-Life in Patients with
      Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized,
      Controlled Phase 3 Clinical Trials.
AB  - INTRODUCTION: Patients with moderate-to-severe atopic dermatitis (AD) report a
      multidimensional disease burden that includes impaired health-related quality-of
      life (HRQoL). Changes in overall health status and specific dimensions that
      contribute to HRQoL were evaluated in adults with moderate-to-severe AD who
      participated in phase 3 clinical trials of dupilumab, which is a fully human
      monoclonal antibody that inhibits signaling of cytokines IL-4 and IL-13. METHODS:
      Two dupilumab phase 3 clinical trials of identical design included the 5
      dimension 3-level EuroQol (EQ-5D) as a measure of HRQoL. EQ-5D data from the two
      trials were pooled in an analysis that, using analysis of covariance, compared
      subcutaneous dupilumab 300 mg once weekly (qw) or every 2 weeks (q2w) versus
      placebo for EQ-5D utility score change from baseline overall and for clinical
      responders. The proportions of patients who reported different levels of problems
      on the individual dimension of the EQ-5D were also compared by treatment group.
      RESULTS: Patients (n = 1379) were 57.9% male with a mean (SD) age of 38.3 (14.3)
      years; baseline EQ-5D utility scores ranged from 0.611 to 0.629 across treatment
      groups. EQ-5D least squares mean change from baseline at week 16 was 0.031 with
      placebo, and was significantly greater with dupilumab qw (0.207) and q2w (0.210)
      (both P < 0.0001), which exceeded the minimal clinically important difference and
      resulted in scores that approached population norms. Changes from baseline among
      patients who achieved AD clinical response were greater than changes among the
      total population. Improvements were driven by the individual EQ-5D dimensions
      with the greatest burden at baseline (i.e., pain/discomfort, anxiety/depression
      and usual activities). CONCLUSION: In adults with moderate-to-severe AD,
      dupilumab resulted in improvements in HRQoL that were statistically significant
      relative to placebo and were clinically meaningful. FUNDING: Sanofi and Regeneron
      Pharmaceuticals, Inc. TRIAL REGISTRATION: ClinicalTrials.gov identifiers,
      NCT02277743 and NCT02277769, EudraCT Numbers 2014-001198-15 and 2014-002619-40.

PMID- 28503711
TI  - Bioactivity Improvement of Olea europaea Leaf Extract Biotransformed by
      Wickerhamomyces anomalus Enzymes.
AB  - Olive leaves represent a quantitatively significant by-product of agroindustry.
      They are rich in phenols, mainly oleuropein, which can be hydrolyzed into several
      bioactive compounds, including hydroxytyrosol. In this study, water extract from
      olive leaves 'Biancolilla' was analyzed for polyphenol profile, DPPH (2,2
      diphenyl-1-picrylhydrazyl) radical scavenging activity and protective effect on
      differentiated Caco-2 cells. The efficacy of two enzymatic treatments in
      promoting the release of bioactive phenols was investigated: a) enzymatic extract
      from Wickerhamomyces anomalus, characterized by beta-glucosidase and esterase
      activities; b) commercial beta-glucosidase. Composition and bioactivity of the
      resulting extracts were compared. The results showed that the yeast-treated
      extract presented hydroxytyrosol content and DPPH radical scavenging activity
      comparable to those obtained using commercial beta-glucosidase; however, it was
      showed the additional presence of hydroxycinnamic acids. In experiments on Caco-2
      cells, the leaf extracts promoted the recovery of cell membrane barrier at
      different minimum effective concentrations. The high specificity of W. anomalus
      enzymatic extract may represent an effective tool for the release of bioactive
      phenols from olive by-products.

PMID- 28503708
TI  - Stress and the nonsense-mediated RNA decay pathway.
AB  - Cells respond to internal and external cellular stressors by activating stress
      response pathways that re-establish homeostasis. If homeostasis is not achieved
      in a timely manner, stress pathways trigger programmed cell death (apoptosis) to
      preserve organism integrity. A highly conserved stress pathway is the unfolded
      protein response (UPR), which senses excessive amounts of unfolded proteins in
      the ER. While a physiologically beneficial pathway, the UPR requires tight
      regulation to provide a beneficial outcome and avoid deleterious consequences.
      Recent work has demonstrated that a conserved and highly selective RNA
      degradation pathway-nonsense-mediated RNA decay (NMD)-serves as a major regulator
      of the UPR pathway. NMD degrades mRNAs encoding UPR components to prevent UPR
      activation in response to innocuous ER stress. In response to strong ER stress,
      NMD is inhibited by the UPR to allow for a full-magnitude UPR response. Recent
      studies have indicated that NMD also has other stress-related functions,
      including promoting the timely termination of the UPR to avoid apoptosis; NMD
      also regulates responses to non-ER stressors, including hypoxia, amino-acid
      deprivation, and pathogen infection. NMD regulates stress responses in species
      across the phylogenetic scale, suggesting that it has conserved roles in shaping
      stress responses. Stress pathways are frequently constitutively activated or
      dysregulated in human disease, raising the possibility that "NMD therapy" may
      provide clinical benefit by downmodulating stress responses.

PMID- 28503713
TI  - Development and refinement of the WAItE: a new obesity-specific quality of life
      measure for adolescents.
AB  - BACKGROUND: Few weight-specific outcome measures, developed specifically for
      obese and overweight adolescents, exist and none are suitable for the elicitation
      of utility values used in the assessment of cost effectiveness. OBJECTIVES: The
      development of a descriptive system for a new weight-specific measure. METHODS:
      Qualitative interviews were conducted with 31 treatment-seeking (above normal
      weight status) and non-treatment-seeking (school sample) adolescents aged 11-18
      years, to identify a draft item pool and associated response options. 315
      eligible consenting adolescents, aged 11-18 years, enrolled in weight management
      services and recruited via an online panel, completed two version of a long-list
      29-item descriptive system (consisting of frequency and severity response
      scales). Psychometric assessments and Rasch analysis were applied to the draft 29
      item instrument to identify a brief tool containing the best performing items and
      associated response options. RESULTS: Seven items were selected, for the final
      item set; all displayed internal consistency, moderate floor effects and the
      ability to discriminate between weight categories. The assessment of
      unidimensionality was supported (t test statistic of 0.024, less than the 0.05
      threshold value). CONCLUSIONS: The Weight-specific Adolescent Instrument for
      Economic-evaluation focuses on aspects of life affected by weight that are
      important to adolescents. It has the potential for adding key information to the
      assessment of weight management interventions aimed at the younger population.

PMID- 28503714
TI  - Depression severity and concentration difficulties are independently associated
      with HRQOL in patients with unipolar depressive disorders.
AB  - PURPOSE: Cognitive impairment is a core feature of major depressive disorder
      (MDD), and dysfunctions in this area strongly contribute to MDD-associated
      disability. Whether cognitive impairment has an independent clinical course and a
      unique impact on HRQOL is still debated. We sought to characterize the
      relationship between depression severity and HRQOL, evaluating the burden of
      concentration difficulties on HRQOL. METHODS: Six hundred ninety-two patients
      with unipolar depressive disorders recruited in 19 Italian centers answered a
      self-administered survey (SF-12 questionnaire, socio-demographic information). A
      psychiatrist completed a standardized data collection form encompassing a
      depression severity scale (MADRS) and clinical information. RESULTS: There was a
      strong graded association between the severity of depressive symptoms and both
      the physical (omega 2 = 0.13; p < 0.01) and mental (omega 2 = 0.34; p < 0.01) SF
      12 domains. Additionally, we observed a strong association between concentration
      difficulties and all HRQOL outcomes independent of other symptoms of depression
      and robust to adjustment for possible confounders. CONCLUSIONS: Our data
      corroborate previous findings suggesting that cognitive impairment is a feature
      of unipolar depressive disorders partially independent of the severity of other
      symptoms, and may represent a specific target of therapy with a strong impact on
      patients' functioning and quality of life.

PMID- 28503715
TI  - Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First
      Indian Patient and a Novel Deletion Affecting IL1RN.
AB  - PURPOSE: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life
      threatening autoinflammatory disease caused by autosomal recessive mutations in
      IL1RN. DIRA presents clinically with early onset generalized pustulosis,
      multifocal osteomyelitis, and elevation of acute phase reactants. We evaluated
      and treated an antibiotic-unresponsive patient with presumed DIRA with
      recombinant IL-1Ra (anakinra). The patient developed anaphylaxis to anakinra and
      was subsequently desensitized. METHODS: Genetic analysis of IL1RN was undertaken
      and treatment with anakinra was initiated. RESULTS: A 5-month-old Indian girl
      born to healthy non-consanguineous parents presented at the third week of life
      with irritability, sterile multifocal osteomyelitis including ribs and clavicles,
      a mild pustular rash, and elevated acute phase reactants. SNP array of the
      patient's genomic DNA revealed a previously unrecognized homozygous deletion of
      approximately 22.5 Kb. PCR and Sanger sequencing of the borders of the deleted
      area allowed identification of the breakpoints of the deletion, thus confirming a
      homozygous 22,216 bp deletion that spans the first four exons of IL1RN. Due to a
      clinical suspicion of DIRA, anakinra was initiated which resulted in an
      anaphylactic reaction that triggered desensitization with subsequent marked and
      sustained clinical and laboratory improvement. CONCLUSION: We report a novel DIRA
      causing homozygous deletion affecting IL1RN in an Indian patient. The mutation
      likely is a founder mutation; the design of breakpoint-specific primers will
      enable genetic screening in Indian patients suspected of DIRA. The patient
      developed anaphylaxis to anakinra, was desensitized, and is in clinical remission
      on continued treatment.

PMID- 28503716
TI  - Dietary inflammatory index and non-Hodgkin lymphoma risk in an Italian case
      control study.
AB  - BACKGROUND: While dietary factors have been shown to play an important etiologic
      role in non-Hodgkin lymphoma (NHL), little is known about the association between
      inflammatory properties of diet and NHL risk. METHODS: We explored the
      association between the dietary inflammatory index (DII) and NHL risk in a
      multicenter Italian case-control study conducted between 1999 and 2014. Cases
      were 536 subjects with incident, histologically confirmed NHL from three areas in
      Italy. Controls were 984 subjects admitted to the same network of hospitals as
      the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were
      computed based on 30 nutrients and food items assessed using a reproducible and
      validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated
      through logistic regression models adjusting for age, total energy intake, and
      other recognized confounding factors. RESULTS: Subjects in the highest quartile
      of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of
      NHL compared with subjects in the lowest quartile (i.e., with the most anti
      inflammatory diets) (ORQuartile4vs1 1.61, 95% confidence interval CI 1.07-2.43; p
      trend = 0.01). Stratified analyses produced stronger associations between DII and
      NHL among males (ORQuartile4vs1 2.14; 95% CI 1.25-3.67) with significant
      heterogeneity (p value = 0.02); when analyzed by histologic subtype, a
      significant association was observed with diffuse large B-cell lymphoma
      (ORQuartile4vs1 1.84; 95% CI 1.09-3.10). CONCLUSION: A pro-inflammatory diet, as
      indicated by higher DII scores, is associated with elevated odds of NHL,
      especially among males.

PMID- 28503718
TI  - Photodithazine photodynamic effect on viability of 9L/lacZ gliosarcoma cell line.
AB  - Even with the advances of conventional treatment techniques, the nervous system
      cancer prognosis is still not favorable to the patient which makes alternative
      therapies needed to be studied. Photodynamic therapy (PDT) is presented as a
      promising therapy, which employs a photosensitive (PS) agent, light wavelength
      suitable for the PS agent, and molecular oxygen, producing reactive oxygen
      species in order to induce cell death. The aim of this study is to observe the
      PDT action in gliosarcoma cell using a chlorin (Photodithazine, PDZ). The
      experiments were done with 9L/lacZ lineage cells, grown in a DMEM medium
      supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin solution
      and put in a culture chamber at 37  degrees C with an atmosphere of 5% CO2. The
      PS agent used was the PDZ to an LED light source device (Biopdi/IRRAD-LED 660) in
      the 660-nm region. The location of the PS agent was analyzed by fluorescence
      microscopy, and cell viability was analyzed by MTT assay (mitochondrial
      activity), exclusion by trypan blue (cell viability), and morphological
      examination through an optical microscope (Leica MD 2500). In the analysis of the
      experiments with PDZ, there was 100% cell death at different concentrations and
      clear morphological differences in groups with and without treatment.
      Furthermore, it was observed that the photodithazine has been focused on all
      nuclear and cytoplasmic extension; however, it cannot be said for sure whether
      the location is in the inside core region or on the plasma membrane. In general,
      the PDZ showed a promising photosensitive agent in PDT for the use of
      gliosarcoma.

PMID- 28503717
TI  - A Review of the Current Challenges Associated with the Development of an
      Artificial Pancreas by a Double Subcutaneous Approach.
AB  - INTRODUCTION: Patients with diabetes type 1 (DM1) struggle daily to achieve good
      glucose control. The last decade has seen a rush of research groups working
      towards an artificial pancreas (AP) through the application of a double
      subcutaneous approach, i.e., subcutaneous (SC) continuous glucose monitoring
      (CGM) and continuous subcutaneous insulin infusion. Few have focused on the
      fundamental limitations of this approach, especially regarding outcome measures
      beyond time in range. METHODS: Based on insulin physiology, the limitations of
      CGM, SC insulin absorption, meal challenge, and physical activity in DM1
      patients, we discuss the limitations of the double SC approach. Finally, we
      discuss safety measures and the achievements reported in some recent AP studies
      that have utilized the double SC approach. RESULTS: Most studies show that a
      double SC AP increases the time in range compared to a sensor-augmented insulin
      pump and shortens the time in hypoglycemia. Despite these achievements, the
      proportion of time spent in hyperglycemia is still roughly 20-40%, and
      hypoglycemia is still present 1-4% of the time. The main factors limiting further
      progress are the latency of SC CGM (at least 5-10 min) and the slow
      pharmacokinetics of SC-delivered fast-acting insulin. The maximum blood insulin
      level is reached after 45 min and the maximum glucose-lowering effect is observed
      after 1.5-2 h, while the glucose-lowering effect lasts for at least 5 h.
      CONCLUSIONS: Although using a double SC AP leads to significant improvements in
      glucose control, the SC approach has severe limitations that hamper further
      progress towards a robust AP.

PMID- 28503719
TI  - Radiation and depression associated with complications of tissue expander
      reconstruction.
AB  - PURPOSE: Rates of implant failure, wound healing delay, and infection are higher
      in patients having radiation therapy (RT) after tissue expander (TE) and
      permanent implant reconstruction. We investigated pretreatment risk factors for
      TE implant complications. PATIENTS AND METHODS: 127 breast cancer patients had TE
      reconstruction and radiation. For 85 cases of bilateral TE reconstruction, the
      non-irradiated breast provided an internal control. Comparison of differences in
      means for continuous variables used analysis of variance, then multiple pairwise
      comparisons with Bonferroni correction of p value. RESULTS: Mean age was 53 +/-
      10.1 years with 14.6% African-American. Twelve (9.4%) were BRCA positive (9
      BRCA1, 4 BRCA2, 1 Both). Complications were: Grade 0 (no complication; 43.9%),
      Grade 1 (tightness and/or drifting of implant or Baker Grade II capsular
      contracture; 30.9%), Grade 2 (infection, hypertrophic scarring, or incisional
      necrosis; 9.8%), Grade 3 (Baker Grade III capsular contracture, wound dehiscence,
      or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of
      implant, or Baker Grade IV capsular contracture; 9.8%). 15.3% (19 cases)
      experienced Grade 3 or 4 complication and 9.8% (12 cases) had Grade 4
      complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3-4
      complications. For BMI, there was no significant difference by category as
      defined by the CDC (p = 0.91). Patients with depression were more likely to
      experience Grade 3 or 4 complication (29.4 vs 13.2%; p = 0.01). Using multiple
      logistic regression to predict the probability of a Grade 3 or 4 complications in
      patients with depression were found to be 4.2 times more likely to have a Grade 3
      or 4 complication (OR = 4.2, p = 0.03). CONCLUSIONS: Higher rates of TE
      reconstruction complications are expected in patients receiving radiotherapy. An
      unexpected finding was that patients reporting medical history of depression
      showed statistically significant increase in complication rates.

PMID- 28503720
TI  - Contribution of germline mutations in cancer predisposition genes to tumor
      etiology in young women diagnosed with invasive breast cancer.
AB  - PURPOSE: Although breast cancer in young women accounts for <10% of diagnoses
      annually, tumors in young patients exhibit more aggressive characteristics and
      higher mortality rates. Determination of the frequency of germline mutations in
      cancer predisposition genes is needed to improve the understanding of breast
      cancer etiology in young women. METHODS: All female patients enrolled in the
      Clinical Breast Cancer Project between 2001 and 2015 and diagnosed with invasive
      breast cancer before age 40 were included in this study. Family history was
      classified using the NCCN Familial Risk Assessment guidelines. Targeted
      sequencing of 94 cancer predisposition genes was performed using peripheral blood
      DNA. Variants were detected using VariantStudio and classified using ClinVar.
      RESULTS: Seven percent (141/1980) of patients were young women and 44 had a
      significant family history. Sequencing was completed for 118 women with genomic
      DNA. Pathogenic mutations were present in 27 patients: BRCA1 (n = 10), BRCA2 (n =
      12), TP53 (n = 1), and CHEK2 (n = 4). Mutations classified as pathogenic were
      also detected in APC (n = 1) and MUTYH (n = 2). Variants of uncertain
      significance (VUS) were detected in an additional 17 patients in ten genes.
      DISCUSSION: Pathogenic mutations in high- and moderate-risk breast cancer genes
      were detected in 23% of young women with an additional 3% having pathogenic
      mutations in colon cancer predisposition genes. VUS were observed in 14% of women
      in genes such as ATM, BRCA2, CDH1, CHEK2, and PALB2. Identification of those non
      genetic factors is critical to reduce the burden of breast cancer in this
      population.

PMID- 28503721
TI  - Limited influence of germline genetic variation on all-cause mortality in women
      with early onset breast cancer: evidence from gene-based tests, single-marker
      regression, and whole-genome prediction.
AB  - PURPOSE: Women diagnosed with breast cancer have heterogeneous survival outcomes
      that cannot be fully explained by known prognostic factors, and germline
      variation is a plausible but unconfirmed risk factor. METHODS: We used three
      approaches to test the hypothesis that germline variation drives some differences
      in survival: mortality loci identification, tumor aggressiveness loci
      identification, and whole-genome prediction. The 2954 study participants were
      women diagnosed with breast cancer before age 50, with a median follow-up of 15
      years who were genotyped on an exome array. We first searched for loci in gene
      regions that were associated with all-cause mortality. We next searched for loci
      in gene regions associated with five histopathological characteristics related to
      tumor aggressiveness. Last, we also predicted 10-year all-cause mortality on a
      subset of 1903 participants (3,245,343 variants after imputation) using whole
      genome prediction methods. RESULTS: No risk loci for mortality or tumor
      aggressiveness were identified. This null result persisted when restricting to
      women with estrogen receptor-positive tumors, when examining suggestive loci in
      an independent study, and when restricting to previously published risk loci.
      Additionally, the whole-genome prediction model also found no evidence to support
      an association. CONCLUSION: Despite multiple complementary approaches, our study
      found no evidence that mortality in women with early onset breast cancer is
      influenced by germline variation.

PMID- 28503722
TI  - Fertility preservation with ovarian stimulation and time to treatment in women
      with stage II-III breast cancer receiving neoadjuvant therapy.
AB  - PURPOSE: To determine whether fertility preservation with ovarian stimulation
      (OS) results in treatment delay in breast cancer (BC) patients receiving
      neoadjuvant therapy (NAT). METHODS: This is a retrospective study of women
      screened for the prospective neoadjuvant ISPY2 trial at the University of
      California San Francisco. All patients were <43, had stage II-III BC, and
      received neoadjuvant therapy. Time to initiation of NAT was compared between
      women who underwent OS (STIM) and women who did not (control). Patient and tumor
      characteristics, as well as oncologic outcomes, were compared between STIM and
      control groups. RESULTS: 82 patients were included (34 STIM and 48 control). STIM
      patients were overall younger (mean = 35 vs. 36.9 years old, p = 0.06), and more
      likely to be childless (79.4 vs 31.2%, p < 0.0001) than controls. Mean time from
      diagnosis to initiation of NAT was 40 days, with no significant difference
      between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean
      time from diagnosis to fertility consultation was 16.3 days. With median follow
      up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR,
      recurrence, and death were similar in both groups. Six of 34 STIM patients have
      undergone embryo transfer, resulting in one patient with two live births.
      CONCLUSION: Fertility preservation with OS can be performed in the neoadjuvant
      setting without delay in initiation of systemic therapy and should be discussed
      with all early-stage BC patients of reproductive age.

PMID- 28503723
TI  - Risk of death from cardiovascular disease following breast cancer: a systematic
      review.
AB  - PURPOSE: Breast cancer incidence and survival is high, which results in high
      prevalence of breast cancer survivors. The risk of (death from) cardiovascular
      disease (CVD) is higher in patients exposed to cardiotoxic treatments, in
      particular if they have pre-existing CVD risk factors. This study systematically
      summarized the risk of death from CVD following breast cancer. METHODS: Databases
      of Medline, Embase, and the Cochrane Library were systematically searched using
      the following terms and synonyms: breast cancer, cardiovascular disease, and
      cause of death. Articles reporting on both risk and risk factors of CVD mortality
      following breast cancer were eligible for inclusion. The methodological quality
      of each article was assessed using the Newcastle Ottawa quality assessment scale
      for cohort studies. RESULTS: Fourteen articles were included assessing the risk
      of CVD mortality among 1,217,910 women with breast cancer. The methodological
      quality was high for the majority of the studies. Studies were heterogeneous in
      design, study population, length of follow-up, CVD outcomes, and risk factors.
      1.6-10.4% of all women with breast cancer died of CVD. Women with breast cancer
      had a higher risk of CVD mortality than women from the general population. The
      risk of CVD mortality was higher among women with breast cancer with older age at
      diagnosis, left-sided tumor, diagnosis in an earlier calendar period, and black
      ethnic origin. CONCLUSIONS: CVD is an important cause of death following breast
      cancer. Identification of patients at high risk of CVD is important to optimize
      CVD prevention and tailor breast cancer treatment.

PMID- 28503724
TI  - Root resorption during orthodontic treatment with Invisalign(r): a radiometric
      study.
AB  - BACKGROUND: Root resorption (RR) is described as a permanent loss of tooth
      structure from the root apex. Many reports in the literature indicate that
      orthodontically treated patients are more likely to have severe apical root
      shortening, interesting mostly maxillary, followed by mandibular incisors. The
      aim of the study was to investigate the incidence and severity of RR in adult
      patients treated with aligners. The study group consisted of 71 class I adult
      healthy patients (mean age 32.8 +/- 12.7) treated with aligners (Invisalign(r),
      Align Technologies, Santa Clara, CA, USA). All incisors, canines, upper first
      premolars, and first molars were assessed. Root and crown lengths of 1083 teeth
      were measured in panoramic radiographs at the beginning (T0) and at the end (T1)
      of clear aligner therapy. Individual root-crown ratio (RCR) of each tooth and
      therefore the relative changes of RCR (rRCR) were determined. A decrease of rRCR
      was assessed as a reduction of the root length during treatment. RESULTS: All
      patients had a minimum of one teeth affected with a reduction of root length, on
      average 6.38 +/- 2.28 teeth per patient. Forty one, 81% of the 1083, measured
      teeth presented a reduction of the pre-treatment root length. A reduction in
      percentage of >0% up to 10% was found in 25.94% (n = 281), a distinct reduction
      of >10% up to 20% in 12.18% (n = 132) of the sample. 3.69% (n = 40) of the teeth
      were affected with a considerable reduction (>20%). CONCLUSIONS: Orthodontic
      treatment with Invisalign(r) aligners could lead to RR. However, its incidence
      resulted to be very similar to that described for orthodontic light forces, with
      an average percentage of RR < 10% of the original root length.

PMID- 28503725
TI  - Posterior teeth angulation in non-extraction and extraction treatment of anterior
      open-bite patients.
AB  - BACKGOUND: This study cephalometrically evaluated the posterior teeth angulation
      changes of anterior open-bite non-extraction and extraction treatment in the
      permanent dentition, with anterior vertical elastics. METHODS: The sample
      consisted of initial and final lateral headfilms of 60 patients divided into 2
      groups: Group 1 consisted of 30 patients treated with non-extraction with an
      initial mean age of 15.26 years and treated with fixed appliances for a mean
      period of 2.46 years. Group 2 consisted of 30 patients treated with extractions,
      with an initial mean age of 14.03 years, and treated with fixed appliances for a
      mean period of 2.49 years. Within-group treatment changes were evaluated with
      paired t tests. Results were considered statistically significant at P < 0.05.
      RESULTS: The mandibular posterior teeth were significantly uprighted in both
      groups with both treatment protocols. CONCLUSIONS: Correction of anterior open
      bite with either non-extraction or extractions with continuous archwires and
      vertical anterior elastics uprights the mandibular posterior teeth.

PMID- 28503727
TI  - Serotonin-norepinephrine reuptake inhibitors and the influence of binding
      affinity (Ki) on analgesia.
AB  - WHAT IS KNOWN AND OBJECTIVE: Serotonin-norepinephrine reuptake inhibitors (SNRIs)
      are commonly used for various psychiatric conditions and neuropathic pain
      syndromes. SNRIs inhibit the reuptake of serotonin (5-HT) and norepinephrine
      (NE); however, NE reuptake inhibition is thought to be the primary mediator for
      their analgesic effect. COMMENT: Key differences in pharmacodynamics and receptor
      affinities exist between SNRIs. The selectivity for each monoamine differs among
      SNRIs based on the agent's affinity and activity at the monoamine reuptake
      transporter. We review differences in receptor affinities and monoamine
      selectivity among SNRIs and the corresponding clinical impact. WHAT IS NEW AND
      CONCLUSION: The varying selectivity for 5-HT and NE among the SNRIs may help
      explain the therapeutic dosing required for neuropathic pain as well as dose
      related adverse effects. It is important to understand the pharmacologic
      differences among SNRIs, in addition to the data from clinical trials, to guide
      their safe and effective use.

PMID- 28503728
TI  - Female undergraduate's perceptions of intrusive behavior in 12 countries.
AB  - The present study examines young women's (N = 1,734) perceptions of the
      unacceptability of 47 intrusive activities enacted by men. Female undergraduate
      psychology students from 12 countries (Armenia, Australia, England, Egypt,
      Finland, India, Indonesia, Italy, Japan, Portugal, Scotland, Trinidad) indicated
      which of 47 intrusive activities they considered to be unacceptable. Responses
      were compared with parasite-stress values, a measure of global gender equality
      and Hofstede's dimensions of national cultures. There was no unanimous agreement
      on any of the items, even for those relating to forced sexual violence. Cluster
      analysis yielded four clusters: "Aggression and surveillance" (most agreement
      that the constituent items were unacceptable), "Unwanted attention," "Persistent
      courtship and impositions," and "Courtship and information seeking" (least
      agreement that the constituent items were unacceptable). There were no
      significant relationships between the "Aggression and surveillance" or "Courtship
      and information seeking" clusters and the measure of gender equality, Hofstede's
      dimensions of national cultures or the measure of parasite stress. For the
      "Unwanted attention" and "Persistent courtship and impositions" clusters, women
      residing in countries with higher gender inequality and higher parasite-stress
      were less accepting of behavior associated with uncommitted sexual relations, and
      women in more individualistic societies with higher levels of gender equality
      were less accepting of monitoring activities. Culture may take precedence over
      personal interpretations of the unacceptability of intrusive behavior that is not
      obviously harmful or benign in nature.

PMID- 28503726
TI  - Baroreflex dysfunction and augmented sympathetic nerve responses during mental
      stress in veterans with post-traumatic stress disorder.
AB  - KEY POINTS: Patients with post-traumatic stress disorder (PTSD) are at a
      significantly higher risk of developing hypertension and cardiovascular disease.
      The mechanisms underlying this increased risk are not known. Studies have
      suggested that PTSD patients have an overactive sympathetic nervous system (SNS)
      that could contribute to cardiovascular risk; however, sympathetic function has
      not previously been rigorously evaluated in PTSD patients. Using direct
      measurements of sympathetic nerve activity and pharmacological manipulation of
      blood pressure, we show that veterans with PTSD have augmented SNS and
      haemodynamic reactivity during both combat-related and non-combat related mental
      stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and
      increased inflammation. Identifying the mechanisms contributing to increased
      cardiovascular (CV) risk in PTSD will pave the way for developing interventions
      to improve sympathetic function and reduce CV risk in these patients. ABSTRACT:
      Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular
      (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic
      nervous system (SNS) and haemodynamic reactivity during mental stress, as well as
      impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy
      Veterans with combat-related PTSD were compared with 14 matched Controls without
      PTSD.  Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP)
      and electrocardiography were measured at baseline, as well as during two types of
      mental stress:  combat-related mental stress using virtual reality combat
      exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A
      cold pressor test (CPT) was administered for comparison. BRS was tested using
      pharmacological manipulation of BP via the Modified Oxford technique at rest and
      during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline
      characteristics, MSNA and haemodynamics were similar between the groups. In PTSD
      vs. Controls, MSNA (+8.2 +/- 1.0 vs. +1.2 +/- 1.3 bursts min-1 , P < 0.001) and
      heart rate responses (+3.2 +/- 1.1 vs. -2.3 +/- 1.0 beats min-1 , P = 0.003) were
      significantly augmented during VRCE.  Similarly, in PTSD vs. Controls, MSNA
      (+21.0 +/- 2.6 vs. +6.7 +/- 1.5 bursts min-1 , P < 0.001) and diastolic BP
      responses (+6.3 +/- 1.0 vs. +3.5 +/- 1.0 mmHg, P = 0.011) were significantly
      augmented during MA but not during CPT (P = not significant). In the PTSD group,
      sympathetic BRS (-1.2 +/- 0.2 vs. -2.0 +/- 0.3 burst incidence mmHg-1 , P =
      0.026) and cardiovagal BRS (9.5 +/- 1.4 vs. 23.6 +/- 4.3 ms mmHg-1 , P = 0.008)
      were significantly blunted at rest. PTSD patients had significantly higher highly
      sensitive-C-reactive protein levels compared to Controls (2.1 +/- 0.4 vs. 1.0 +/-
      0.3 mg L-1 , P = 0.047). Augmented SNS and haemodynamic responses to mental
      stress, blunted BRS and inflammation may contribute to an increased CV risk in
      PTSD.

PMID- 28503729
TI  - Fully integrated 3D high-resolution multicontrast abdominal PET-MR with high scan
      efficiency.
AB  - PURPOSE: To provide 3D multicontrast anatomical MR with high isotropic resolution
      and metabolic positron emission tomography (PET) images using a respiratory
      motion-compensated simultaneous PET-MR examination with high scan efficiency.
      THEORY AND METHODS: Standard abdominal PET-MR examinations combine MR data
      obtained during multiple breath-holds with free-breathing PET acquisitions,
      limiting the achievable image resolution and potentially causing misalignment
      errors between breath-hold and free-breathing data. Here, a 3D free-breathing PET
      MR acquisition is presented, yielding T1 and T2 -weighted MR images with an
      isotropic resolution of 1.5 mm3 . In addition, nonrigid respiratory motion
      information and respiratory-resolved attenuation-correction maps are obtained
      without an increase in scan time. Motion information is used in motion
      compensated image reconstructions to improve MR and PET image quality while
      shortening scan times. RESULTS: The proposed approach was evaluated in 11
      oncology patients and provided respiratory motion information with an accuracy of
      1.3 +/- 0.1 mm. Sharpness of anatomical features was increased by 19 +/- 13%
      compared with the uncorrected MR images in a 54 +/- 26% shorter scan time than a
      gated MR acquisition. The MR-based motion information improved uptake values (75
      +/- 94%) and resolution (16 +/- 27%) of simultaneously acquired PET images.
      CONCLUSIONS: The proposed method provides motion-compensated 3D high-quality MR
      and PET images in a comprehensive and highly efficient examination. Magn Reson
      Med 79:900-911, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 28503730
TI  - Cardiopulmonary and sedative effects of intravenous or epidural methadone in
      conscious dogs.
AB  - Cardiopulmonary and sedative effects of intravenous or epidural methadone were
      compared. Six beagles were randomly assigned to group MIV (methadone 0.5 mg/kg IV
      + NaCl 0.9% epidurally) or MEP (methadone 0.5 mg/kg epidurally + NaCl 0.9% IV).
      Cardiopulmonary, blood gas and sedation were assessed at time (T) 0, 15, 30, 60,
      120, 240 and 480 min after drug administration. Compared to T0, heart rate
      decreased at T15-T120 in MIV (p < .001) and T15-T240 in MEP (p < .05); mean
      arterial pressure was reduced at T15-T60 in MEP (p < .01); respiratory rate was
      higher at T15 and T30 in both groups (p < .05); pH was lower at T15-T120 in MIV
      (p < .01) and T15, T30 and T120 in MEP (p < .05); PaCO2 was higher at T15-T60 in
      MIV (p < .01) and T15, T30 and T120 in MEP (p < .01); sedation scores were higher
      at T15 and T30 in MIV and T15-T60 in MEP (p < .05). At T120 and T240, sedation
      score was higher in group MEP compared with group MIV (p < .01) In conclusion,
      cardiopulmonary and sedative effects of identical methadone doses are similar
      when administered IV or epidurally to conscious healthy dogs.

PMID- 28503731
TI  - A Microfluidic Ion Pump for In Vivo Drug Delivery.
AB  - Implantable devices offer an alternative to systemic delivery of drugs for the
      treatment of neurological disorders. A microfluidic ion pump (uFIP), capable of
      delivering a drug without the solvent through electrophoresis, is developed. The
      device is characterized in vitro by delivering gamma-amino butyric acid to a
      target solution, and demonstrates low-voltage operation, high drug-delivery
      capacity, and high ON/OFF ratio. It is also demonstrated that the device is
      suitable for cortical delivery in vivo by manipulating the local ion
      concentration in an animal model and altering neural behavior. These results show
      that uFIPs represent a significant step forward toward the development of
      implantable drug-delivery systems.

PMID- 28503734
TI  - Retropubic tissue fixation system tensioned mini-sling carried out under local
      anesthesia cures stress urinary incontinence and intrinsic sphincter deficiency:
      1-year data.
AB  - OBJECTIVES: To assess the outcomes of the tissue fixation system midurethral
      sling for the treatment of intrinsic sphincter deficiency. METHODS: We
      retrospectively studied a total of 96 intrinsic sphincter deficiency patients
      treated with the tissue fixation system midurethral sling at Yokohama Motomachi
      Women's Clinic from 2006 to 2015. We evaluated intraoperative and 1-year
      postoperative results. Regarding the cure rate, we divided patients into three
      groups: (i) patients with maximum urethral closure pressure <20 and Valsalva leak
      point pressure <65 combined (n = 17); (ii) patients with maximum urethral closure
      pressure <20 (n = 55); and (iii) patients with Valsalva leak point pressure <65
      (n = 47). RESULTS: The median age was 63 years (range 38-89 years). The median
      operating time including local anesthesia was 24 min (range 12-55 min) and median
      blood loss was 5.0 mL (range 3-69 mL). All operations were day surgery under
      local anesthesia. Postoperative pain was minimal. All patients were discharged
      the same day. There were no intraoperative complications except one bladder
      perforation. There were no tape rejections. The 1-year postoperative cure rates
      were: 88.2% among patients with maximum urethral closure pressure <20 and
      Valsalva leak point pressure <65, 90.9% for patients with maximum urethral
      closure pressure <20, and 85.1% among patients with Valsalva leak point pressure
      <65. CONCLUSIONS: The tissue fixation system midurethral sling operation is a
      simple, safe and effective operation for older women with intrinsic sphincter
      deficiency, and it can be carried out under local anesthesia.

PMID- 28503732
TI  - Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI.
AB  - PURPOSE: To characterize the relaxation properties of reactive oxygen species
      (ROS) for the development of endogenous ROS contrast magnetic resonance imaging
      (MRI). MATERIALS AND METHODS: ROS-producing phantoms and animal models were
      imaged at 9.4T MRI to obtain T1 and T2 maps. Egg white samples treated with
      varied concentrations of hydrogen peroxide (H2 O2 ) were used to evaluate the
      effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes
      due to H2 O2 treatment in egg white were also monitored. The influences from H2
      O2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution
      producing no ROS. In addition, dynamic temporal changes of T1 in H2 O2 -treated
      egg white samples were used to estimate ROS concentration over time and hence the
      detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of
      ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of
      in vivo ROS MRI with T1 mapping acquired using an inversion recovery sequence was
      demonstrated with a well-established rotenone-treated mouse model (n = 6).
      RESULTS: pH and temperature changes in treated egg white samples were
      insignificant (<0.1 unit and <1 degrees C, respectively). T1 relaxation time in
      the H2 O2 -treated egg white was reduced significantly (P < 0.05), while there
      was only small reduction in T2 (<10%). In the H2 O2 -treated BSA solution that
      produce no ROS, there was a small change in T1 due to H2 O2 itself (+/-1%),
      although a significant T2 -shortening effect was observed (>10%, P < 0.05). Also,
      there was a small reduction in T1 (13 +/- 1%) and T2 (1 +/- 2%) from molecular
      oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T1
      relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 * 107 vs.
      0.9 s-1 .mM-1 ). Finally, significantly reduced T1 was observed in rotenone
      treated mouse brain (5.1 +/- 2.5%, P < 0.05). CONCLUSION: We demonstrated in the
      study that endogenous ROS MRI based on the paramagnetic effect has sensitivity
      for in vitro and in vivo applications. LEVEL OF EVIDENCE: 2 Technical Efficacy
      Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.

PMID- 28503733
TI  - Long-term safety from transmission of porcine endogenous retrovirus after pig-to
      non-human primate corneal transplantation.
AB  - BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus
      (PERV) has been considered as one of the main hurdles in xenotransplantation and
      therefore should be elucidated prior to the clinical use of porcine corneal
      grafts. Accordingly, an investigation was performed to analyze the infectivity of
      PERVs from porcine keratocytes to human cells, and the long-term risk of
      transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal
      transplantation models. METHODS: The infectivity of PERVs from the SNU miniature
      pig keratocytes was investigated by coculture with a human embryonic kidney cell
      line. Twenty-two rhesus macaques underwent xenocorneal transplantation as
      follows: (i) group 1 (n=4): anterior lamellar keratoplasty (LKP) with freshly
      preserved porcine corneas, (ii) group 2 (n=5): anterior LKP with decellularized
      porcine corneas followed by penetrating keratoplasty (PKP) with allografts, (iii)
      group 3 (n=3): PKP under steroid-based immunosuppression, (iv) group 4 (n=4): PKP
      under anti-CD154 antibody-based immunosuppression, (v) group 5 (n=4): deep
      anterior LKP with freshly preserved porcine corneas under anti-CD40 antibody
      based immunosuppression, and (vi) group 6 (n=2): PKP under anti-CD40 antibody
      based immunosuppression. Postoperative blood samples were serially collected, and
      tissue samples were obtained from thirteen different organs at the end of each
      experiment. The existence of PERV DNA and RNA was investigated using PCR and RT
      PCR. RESULTS: Using two independent in vitro infectivity tests, neither PERV pol
      nor pig mitochondrial cytochrome oxidase II was detected after 41 and 92 days of
      coculture, respectively. After xenocorneal transplantation, a total of 257 serial
      peripheral blood mononuclear cell samples, 34 serial plasma samples, and 282
      tissue samples were obtained from the NHP recipients up to 1176 days post
      transplantation. No PERV transmission was evident in any samples. CONCLUSIONS:
      Within the limits of this study, there is no evidence to support any risk of PERV
      transmission from porcine corneal tissues to NHP recipients, despite the
      existence of PERV-expressing cells in porcine corneas.

PMID- 28503735
TI  - WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and
      cerebral hypoplasia: A consistent neurodevelopmental syndrome.
AB  - The advancement in genomic sequencing has greatly improved the diagnostic yield
      for neurodevelopmental disorders and led to the discovery of large number of
      novel genes associated with these disorders. WDR45B has been identified as a
      potential intellectual disability gene through genomic sequencing of 2 large
      cohorts of affected individuals. In this report we present 6 individuals from 3
      unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T
      (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals
      shared a similar phenotype including profound development delay, early-onset
      refractory epilepsy, progressive spastic quadriplegia and contractures, and brain
      malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white
      matter volume, and thinning of cerebral gray matter. The consistency in the
      phenotype strongly supports that WDR45B is associated with this disease.

PMID- 28503737
TI  - Inducing Complexity in Intermetallics through Electron-Hole Matching: The
      Structure of Fe14 Pd17 Al69.
AB  - We illustrate how the crystal structure of Fe14 Pd17 Al69 provides an example of
      an electron-hole matching approach to inducing frustration in intermetallic
      systems. Its structure contains a framework based on IrAl2.75 , a binary compound
      that closely adheres to the 18-n rule. Upon substituting the Ir with a mixture of
      Fe and Pd, a competition arises between maintaining the overall ideal electron
      concentration and accommodating the different structural preferences of the two
      elements. A 2*2*2 supercell results, with Pd- and Fe-rich regions emerging. Just
      as in the original IrAl2.75 phase, the electronic structure of Fe14 Pd17 Al69
      exhibits a pseudogap at the Fermi energy arising from an 18-n bonding scheme. The
      electron-hole matching approach's ability to combine structural complexity with
      electronic pseudogaps offers an avenue to new phonon glass-electron crystal
      materials.

PMID- 28503736
TI  - Hydrogen sulfide pretreatment improves mitochondrial function in myocardial
      hypertrophy via a SIRT3-dependent manner.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulfide (H2 S) is a gaseous signal molecule with
      antioxidative properties. Sirtuin 3 (SIRT3) is closely associated with
      mitochondrial function and oxidative stress. The study was to investigate whether
      and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner.
      EXPERIMENTAL APPROACH: Neonatal rat cardiomyocytes were pretreated with NaHS (50
      MUM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was
      silenced with siRNA technology. SIRT3 promoter activity and expression, cell
      surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate
      and membrane potential were measured. Male 129S1/SvImJ [wild-type (WT)] and SIRT3
      knockout (KO) mice were injected with NaHS (50 MUmol.kg-1 .day-1 ; i.p.) followed
      by transverse aortic constriction (TAC). Echocardiography, heart mass,
      mitochondrial ultrastructure, volume and number, oxidative stress, mitochondria
      fusion and fission-related protein expression were measured. KEY RESULTS: In
      vitro, NaHS increased SIRT3 promoter activity and SIRT3 expression in Ang II
      induced cardiomyocyte hypertrophy. SIRT3 silencing abolished the ability of NaHS
      to reverse the Ang II-induced cardiomyocyte hypertrophy, mitochondrial function
      impairment and permeability potential dysfunction, along with the decline in
      FOXO3a and SOD2 expression. In vivo, after TAC. NaHS attenuated myocardial
      hypertrophy, inhibited oxidative stress, improved mitochondrial ultrastructure,
      suppressed mitochondrial volume but increased mitochondrial numbers, enhanced
      OPA1, MFN1 and MFN2 expression but suppressed DRP1 and FIS1 expression in WT mice
      but not in SIRT3 KO mice CONCLUSION AND IMPLICATIONS: NaHS improved mitochondrial
      function and inhibited oxidative stress in myocardial hypertrophy in a SIRT3
      dependent manner. LINKED ARTICLES: This article is part of a themed section on
      Spotlight on Small Molecules in Cardiovascular Diseases. To view the other
      articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

PMID- 28503739
TI  - The Bleeding on Brushing Index: a novel index in preventive dentistry.
AB  - BACKGROUND: The aim of this study was to evaluate the suitability of a
      dichotomous index, based on a special interdental brushing tool, to detect
      initial pathological processes in interproximal areas. Furthermore, different
      techniques of interdental hygiene were compared. METHODS: Participants (n = 108)
      were instructed to clean their teeth using the Bass technique and were randomly
      assigned to three groups according to the type of interdental cleaning used:
      group A, use of interdental brushes; group B, no interdental hygiene (the control
      group); and group C, use of dental floss. Approximal Plaque Index (API), Plaque
      Index (PI), modified Sulcus Bleeding Index (mSBI) and the Bleeding on Brushing
      Index (BOB) were measured at baseline, and after 2 (t1) and 4 (t2) weeks.
      Statistical analysis was performed using the Wilcoxon test and the Mann-Whitney U
      test. RESULTS: One-hundred and six participants completed the study. The BOB
      decreased significantly in all groups (P < 0.001) with the most pronounced
      reduction being recorded for group A (baseline: 49.3 +/- 23.0%; 4 weeks: 5.1 +/-
      6.9%). Also, the mSBI (P < 0.001) decreased significantly in all groups during
      the study. The API appeared to be less affected by the oral hygiene than other
      indices. The highest correlation was observed between BOB and mSBI (r = 0.785, P
      < 0.001). CONCLUSION: The BOB is a valuable complement for the existing array of
      indices in preventive dentistry, and is able to detect potential pathological
      processes in interproximal spaces. Additionally, this study suggests that
      interdental hygiene with individually selected brushes is superior to flossing.
      CLINICAL RELEVANCE: With the BOB, gingival inflammation can be demonstrated to
      patients, which could increase compliance.

PMID- 28503738
TI  - Targeting human telomeric G-quadruplex DNA with antitumour natural alkaloid
      aristololactam-beta-D-glucoside and its comparison with daunomycin.
AB  - Study on anticancer agents that act via stabilization of telomeric G-quadruplex
      DNA has emerged as novel and exciting field for anticancer drug discovery. The
      interaction of carbohydrate containing anticancer alkaloid aristololactam-beta-D
      glucoside (ADG) with human telomeric G-quadruplex DNA sequence was characterized
      by different biophysical techniques. The binding parameters were compared with
      daunomycin (DAN), a well-known chemotherapeutic drug. The Scatchard binding
      isotherms revealed noncooperative binding for both with the binding affinity
      values of (1.01 +/- 0.05) * 106 and (1.78 +/- 0.18) * 106 M-1 for ADG and DAN,
      respectively. Circular dichroism, ferrocyanide quenching study, anisotropy study,
      thiazole orange displacement, optical melting, differential scanning calorimetry
      study, and molecular docking study suggest significant stacking and stabilizing
      efficiency of ADG with comparison to DAN. The energetics of the interaction for
      ADG and DAN revealed that both reactions were predominantly entropy driven.
      Negative heat capacity values were obtained from the temperature dependence of
      the enthalpy change. The standard molar Gibbs energy change exhibited only
      marginal alterations with temperature suggesting the occurrence of enthalpy
      entropy compensation. These findings indicate that ADG can act as a stabilizer of
      telomeric G-quadruplex DNA and thereby can be considered as a potential
      telomerase inhibitor.

PMID- 28503741
TI  - The effect of autologous activated platelet-rich plasma injection on female
      pattern hair loss: A randomized placebo-controlled study.
AB  - BACKGROUND: Hair is an essential part of a woman's appearance and attractiveness.
      This is reflected in the predominantly psychological morbidity that can be
      associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used
      in numerous fields of medicine. Recently, PRP has received growing attention as a
      potential therapeutic tool for hair loss. OBJECTIVE: To evaluate the efficacy and
      safety of autologous platelet-rich plasma in the treatment of female pattern hair
      loss. MATERIALS AND METHODS: Thirty female patients with female pattern hair loss
      were randomly assigned to receive autologous PRP injection into a selected area,
      and another area was injected with normal saline as a placebo. Sessions were
      performed weekly for a maximum total of four sessions. Patients were followed up
      6 months after the end of last session. The outcome was assessed both
      subjectively and objectively. RESULTS: There was a statistical significant
      difference between PRP and placebo areas (P<.005) regarding both hair density and
      hair thickness as measured by a folliscope. The hair pull test became negative in
      PRP-injected areas in 25 patients (83%) with average number of three hairs.
      Global pictures showed a significant improvement in hair volume and quality
      together with a high overall patient satisfaction in PRP-injected sites, and
      these results were maintained during the 6-month follow- up. CONCLUSION: Platelet
      rich plasma injections can be regarded as an alternative for the treatment of
      female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio.

PMID- 28503740
TI  - Weed interference with peppermint (Mentha x piperita L.) and spearmint (Mentha
      spicata L.) crops under different herbicide treatments: effects on biomass and
      essential oil yield.
AB  - BACKGROUND: 'Minor crops' such as spearmint and peppermint are high added value
      crops, despite the fact that their production area is comparably small worldwide.
      The main limiting factor in mint commercial cultivation is weed competition.
      Thus, field experiments were carried out to evaluate the effects of weed
      interference on growth, biomass and essential oil yield in peppermint and
      spearmint under different herbicide treatments. RESULTS: The application of
      pendimethalin and oxyfluorfen provided better control of annual weeds resulting
      in higher crop yield. Additionally, when treated with herbicides both crops were
      more competitive against annual weeds in the second year than in the first year.
      All pre-emergence herbicides increased biomass yield, since pendimethalin,
      linuron and oxyfluorfen reduced the density of annual weeds by 71-92%, 63-74% and
      86-95%, respectively. Weed interference and herbicide application had no effect
      on essential oil content; however, a relatively strong impact on essential oil
      production per cultivated area unit was observed, mainly due to the adverse
      effect of weed interference on plant growth. CONCLUSION: Considering that
      pendimethalin and oxyfluorfen were effective against annual weeds in both
      spearmint and peppermint crops, these herbicides should be included in integrated
      weed management systems for better weed management in mint crops. (c) 2017
      Society of Chemical Industry.

PMID- 28503743
TI  - Benchmarking the research track record and level of appointment of Australian
      occupational therapy academics.
AB  - BACKGROUND: Academic faculty are active contributors to the evidence base of the
      profession. Little is known about the research productivity of Australian
      occupational therapy academics. METHODS: A bibliographic analysis of Australian
      occupational therapy faculty websites and corresponding Scopus citation database
      profiles was conducted. A description of current research productivity benchmarks
      and relationships with holding a doctorate, academic appointment level and
      institutional characteristics were explored. RESULTS: The median H-index of
      Clinical and Associate Lecturers was 0, 1 for Lecturers, 4 for Senior Lecturers,
      7.5 for Associate Professors and 13 for Professors. The number of publications
      and number of citing documents follows a Pareto tendency, where 20% of
      researchers are responsible for around 80% of the research track record of
      Australian occupational therapy academics. CONCLUSION: The findings provide a
      benchmark for Australian occupational therapy faculty research track records and
      associations with appointment levels. This benchmark differs across countries and
      disciplines. The results raise considerations for enhancing the overall research
      track record of occupational therapy academics.

PMID- 28503742
TI  - The ERN1 transcription factor gene is a target of the CCaMK/CYCLOPS complex and
      controls rhizobial infection in Lotus japonicus.
AB  - Bacterial accommodation inside living plant cells is restricted to the nitrogen
      fixing root nodule symbiosis. In many legumes, bacterial uptake is mediated via
      tubular structures called infection threads (ITs). To identify plant genes
      required for successful symbiotic infection, we screened an ethyl
      methanesulfonate mutagenized population of Lotus japonicus for mutants defective
      in IT formation and cloned the responsible gene, ERN1, encoding an AP2/ERF
      transcription factor. We performed phenotypic analysis of two independent L.
      japonicus mutant alleles and investigated the regulation of ERN1 via
      transactivation and DNA-protein interaction assays. In ern1 mutant roots, nodule
      primordia formed, but most remained uninfected and bacterial entry via ITs into
      the root epidermis was abolished. Infected cortical nodule cells contained
      bacteroids, but transcellular ITs were rarely observed. A subset exhibited
      localized cell wall degradation and loss of cell integrity associated with
      bacteroid spread into neighbouring cells and the apoplast. Functional promoter
      studies revealed that CYCLOPS binds in a sequence-specific manner to a motif
      within the ERN1 promoter and in combination with CCaMK positively regulates ERN1
      transcription. We conclude that the activation of ERN1 by CCaMK/CYCLOPS complex
      is an important step controlling IT-mediated bacterial progression into plant
      cells.

PMID- 28503744
TI  - Treatment using tadalafil for severe pre-eclampsia with fetal growth restriction.
AB  - For severe pre-eclampsia (PE) with fetal growth restriction (FGR), the only
      effective treatment is early delivery of the placenta. Clinicians are often
      forced to end the pregnancy because of maternal indications. We report a case of
      severe PE with FGR in which the PE was temporarily improved and pregnancy
      successfully prolonged with tadalafil, a phosphodiesterase 5 inhibitor. A 35-year
      old primigravid woman presented at 27 3/7 weeks of gestation with severe PE and
      FGR. After commencing tadalafil administration, biochemical and angiogenic
      markers improved. Thereafter, hypertension and proteinuria temporarily improved.
      Importantly, the pregnancy was prolonged by 14 days after the initiation of
      tadalafil administration. Tadalafil may be a novel treatment for severe PE with
      FGR to prolong pregnancy.

PMID- 28503745
TI  - Interactions Between phyB and PIF Proteins Alter Thermal Reversion Reactions in
      vitro.
AB  - The dynamic behavior of the plant red/far-red light photoreceptor phytochrome B
      (phyB) has been elucidated in natural and synthetic systems. Red light switches
      phyB from the inactive Pr state to the active Pfr state, a process that is
      reversed by far-red light. Alongside light signals, phyB activity is constrained
      by thermal reversion (that is prominent in the dark) and protein-protein
      interactions between phyB, other phytochrome molecules, and, among others,
      PHYTOCHROME INTERACTING FACTORs (PIFs). Requirements for phyB-PIF association
      have been well studied and are central to light-regulated synthetic tools.
      However, it is unknown whether PIF interactions influence transitions of phyB
      between different conformers. Here, we show that the in vitro thermal reversion
      of phyB involves multiple reactions. Thermal reversion of phyB in vitro is
      inhibited by PIF6, and this effect is observed at all temperatures tested. We
      analyzed our experimental data using a mathematical model containing multiple Pfr
      conformers, in accordance with previous findings. Remarkably, each Pfr conformer
      is differentially regulated by PIF6 and temperature. As a result, we speculate
      that in vivo phytochrome signaling networks may require similar levels of
      complexity to fine-tune responses to the external environment.

PMID- 28503746
TI  - Application of Ultrasound Elastography for Chronic Allograft Dysfunction in
      Kidney Transplantation.
AB  - Interstitial fibrosis is the main characteristic of chronic allograft
      dysfunction, which remains the key factor affecting long-term allograft survival
      after kidney transplantation. Ultrasound elastography (UE), including real-time
      elastography, transient elastography, and acoustic radiation force impulse, has
      been applied widely in breast, thyroid, and liver diseases, especially in the
      assessment of liver fibrosis. Recently, numerous studies have reported the
      efficacy of UE methods in evaluating renal allograft fibrosis. This review aims
      to investigate the clinical applications, limitations, and future roles of UE in
      current clinical practice in light of changing management paradigms. In current
      clinical practice, UE methods, especially transient elastographic measurement,
      appear to be useful for ruling out fibrosis but do not have sufficient accuracy
      to distinguish between various stages of allograft fibrosis. Moreover, there
      remain considerable issues to be solved for the application of UE in kidney
      transplantation. Thus, UE methods cannot replace the crucial role of renal
      allograft biopsy in the diagnosis and evaluation of allograft fibrosis in kidney
      transplantation. Perhaps UE methods could be of more importance in the long-term
      observation and evaluation of allograft fibrosis during follow-up.

PMID- 28503747
TI  - Friends and family: A software program for identification of unrelated
      individuals from molecular marker data.
AB  - The identification of related and unrelated individuals from molecular marker
      data is often difficult, particularly when no pedigree information is available
      and the data set is large. High levels of relatedness or inbreeding can influence
      genotype frequencies and thus genetic marker evaluation, as well as the accurate
      inference of hidden genetic structure. Identification of related and unrelated
      individuals is also important in breeding programmes, to inform decisions about
      breeding pairs and translocations. We present Friends and Family, a Windows
      executable program with a graphical user interface that identifies unrelated
      individuals from a pairwise relatedness matrix or table generated in programs
      such as coancestry and genalex. Friends and Family outputs a list of samples that
      are all unrelated to each other, based on a user-defined relatedness cut-off
      value. This unrelated data set can be used in downstream analyses, such as marker
      evaluation or inference of genetic structure. The results can be compared to that
      of the full data set to determine the effect related individuals have on the
      analyses. We demonstrate one of the applications of the program: how the removal
      of related individuals altered the Hardy-Weinberg equilibrium test outcome for
      microsatellite markers in an empirical data set. Friends and Family can be
      obtained from https://github.com/DeondeJager/Friends-and-Family.

PMID- 28503748
TI  - Cigarette smoking induces only marginal changes in sperm DNA methylation levels
      of patients undergoing intracytoplasmic sperm injection treatment.
AB  - DNA methylation plays important roles in genome stability and regulation of gene
      expression. This study was designed to determine the influence of cigarette
      smoking on sperm DNA methylation. From a genome-wide survey on sperm samples,
      differentially methylated target CpGs should be selected and subjected to local
      deep bisulphite sequencing. Obtained methylation data are compared to sperm
      parameters and (ICSI) outcome. Similar to pilot study, samples were subjected to
      Infinium 450K BeadChip arrays to identify alterations in sperm DNA methylation
      between smokers and nonsmokers males. Routine testing on a significantly altered
      CpG site was performed on more samples using local deep bisulphite sequencing. Of
      approximately 485,000 CpG sites analysed, only seven CpGs were found to show a
      significant DNA methylation difference of >20% with the top six CpGs overlapping
      common SNP sites. The remaining CpG site (cg19455396) is located in intron 12 of
      the TAP2 gene. The results of deep bisulphite sequencing showed only a tendency
      towards hypomethylation in the smoking group. This study could not detect
      biologically relevant CpG positions that are altered in sperm DNA methylation on
      the influence of cigarette smoking beyond individual-specific effects that may be
      caused by other environmental factors.

PMID- 28503749
TI  - A Prospective Evaluation of Transverse Tracheal Sonography During Emergent
      Intubation by Emergency Medicine Resident Physicians.
AB  - OBJECTIVES: Establishing a definitive airway is often the first step in emergency
      department treatment of critically ill patients. Currently, there is no agreed
      upon consensus as to the most efficacious method of airway confirmation. Our
      objective was to determine the diagnostic accuracy of real-time sonography
      performed by resident physicians to confirm placement of the endotracheal tube
      during emergent intubation. METHODS: We performed a prospective cohort study of
      adult patients in the emergency department undergoing emergent endotracheal
      intubation. Thirty emergency medicine residents, who were blinded to end-tidal
      carbon dioxide detection results, performed real-time transverse tracheal
      sonography during intubation to evaluate correct endotracheal tube placement.
      RESULTS: Seventy-two patients were enrolled in the study. Sixty-eight instances
      (94.4%) were interpreted as correct placement in the trachea; 4 (5.6%) were
      interpreted as esophageal, of which 1 was a false-negative finding, therefore
      conferring sensitivity of 98.5% (95% confidence interval, 92.1%-99.9%) and
      specificity of 75.0% (95% confidence interval, 19.4%-99.4%) for correct
      placement. There was no significant difference in accuracy among resident
      sonographers with different levels of residency training. CONCLUSIONS: A simple
      transverse tracheal sonographic examination performed by emergency medicine
      resident physicians can be used as an adjunct to help confirm correct
      endotracheal tube placement during intubation. In our cohort, the level of
      training did not appear to affect the ability of residents to correctly identify
      the endotracheal tube position.

PMID- 28503750
TI  - Comparative effects of liraglutide 3 mg vs structured lifestyle modification on
      body weight, liver fat and liver function in obese patients with non-alcoholic
      fatty liver disease: A pilot randomized trial.
AB  - We compared the effects of weight loss induced by the glucagon-like peptide 1
      agonist liraglutide with a structured lifestyle intervention in obese adults with
      non-alcoholic fatty liver disease (NAFLD). Obese (body mass index >=30 kg/m2 ,
      mean weight 96.0 +/- 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by
      liver fat fraction (LFF) >= 5.5% on magnetic resonance imaging without other
      causes of hepatic steatosis, were randomized to a supervised program of dieting
      (restriction by 400 kilocalories/d) plus moderate-intensity aerobic exercise
      (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved
      for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had
      significant (P < .01) and similar reductions in weight (-3.5 +/- 3.3 vs -3.5 +/-
      2.1 kg, respectively, P = .72), LFF (-8.9 +/- 13.4 vs -7.2% +/- 7.1%, P = .70),
      serum alanine aminotransferase (-42 +/- 46 vs -34 +/- 27 U/L, P = .52) and
      aspartate aminotransferase (-23 +/- 24 vs -18 +/- 15 U/L, P = .53). In this first
      randomized study comparing the 2 weight-loss modalities for improving NAFLD,
      liraglutide was as effective as structured lifestyle modification.

PMID- 28503751
TI  - In vitro evaluation of potential transporter-mediated drug interactions of
      evogliptin.
AB  - To date, little is known about the transporter-mediated drug-drug interaction
      (DDI) potential of evogliptin, a novel DPP-4 inhibitor. The objective of this
      study was to evaluate the DDI potential of evogliptin using various in vitro
      assays in transporter-expressing cell lines. After incubating evogliptin with
      cells overexpressing OAT1, OAT3, OCT2, OATP1B1 and OATP1B3, there was no notable
      cellular accumulation of evogliptin (fold accumulation, 0.41-1.86). In
      bidirectional transport assays using a Caco-2 cell monolayer, a high efflux ratio
      (ER, 522) of evogliptin was observed, which was significantly decreased (97.96%)
      in the presence of a potent P-gp inhibitor. In assays using MDCKII-BCRP cell
      monolayers, by contrast, a low net ER (1.16-1.26) was found. In similar cellular
      uptake and bidirectional studies with probe substrates of P-gp, BCRP, OAT1, OAT3,
      OCT2, OATP1B1 and OATP1B3, the active transport of the substrates was not
      significantly suppressed by evogliptin. These results suggest that evogliptin may
      be a substrate of P-gp, but not a substrate of BCRP, OAT1B1, OAT1B3, OAT1, OAT3
      or OCT2, and not an inhibitor of any of these transporters. Therefore, it could
      be concluded that evogliptin has some DDI potential involving P-gp, but it has
      low potential of DDI mediated by the other transporters.

PMID- 28503752
TI  - Point-of-Care Diagnosis of Cardiac Tamponade Identified by the Flow Velocity
      Paradoxus.
AB  - The presentation of cardiac tamponade is a spectrum from occult to extreme. The
      clinical history, physical exam, electrocardiogram, and radiographic findings of
      tamponade have poor sensitivities and even worse specificities. We use a clinical
      scenario to demonstrate how point-of-care cardiac ultrasound can diagnose
      impending cardiac tamponade in a clinically stable patient. The ultrasound
      finding we recommend is the flow velocity paradoxus, in which respiratory
      variation causes significant changes in transvalvular inflow velocities, which
      are exaggerated when tamponade is present. The management of a pericardial
      effusion depends on its physiologic effect, and point-of-care ultrasound directly
      measures that effect and expedites patient care.

PMID- 28503753
TI  - Distal Forearm Fracture Open Reduction-Internal Fixation: Sonographic Detection
      of Hardware Malalignment and Associated Tendon Injuries Missed by Radiography.
AB  - Tendon injury is a known complication of distal radius fracture plate and screw
      fixation. Targeted musculoskeletal sonography is uniquely capable of assessing
      both tendon integrity and hardware abnormalities not recognized on radiographs.
      Each of the 3 patients described presented with pain after an open reduction
      internal fixation following a distal forearm fracture. In each patient,
      radiographic findings, specifically the hardware position, were interpreted as
      normal. Important radiographically occult observations were subsequently made
      with sonography, including 3 proud screws and tendon injuries, all of which
      required surgical treatment. This case series demonstrates the clinical utility
      of musculoskeletal sonography in symptomatic patients after distal radius open
      reduction-internal fixation with negative radiographic findings. In our practice,
      sonography has been the most useful modality for precluding missing or delaying
      the diagnosis and treatment of these hardware complications. We advocate its use
      as an adjunct in any department performing musculoskeletal imaging.

PMID- 28503754
TI  - An unusual pathological posterior vitreous detachment.

PMID- 28503755
TI  - Wanting to work: managing the sick role in high-stake sickness insurance
      meetings.
AB  - This article respecifies and develops Parsons's sick role theory, focusing on the
      postulate that the sick person must 'want' to get well. Using conversation
      analysis and discursive psychology to study how the psychological term 'want' is
      used in high-stake, multi-professional meetings with sickness benefit claimants
      in Sweden, the article shows how establishing that one 'wants' to get well
      requires extensive interactional work. In the examined meetings, the sick
      person's 'want' formulations make explicit the relationship between 'wants' and
      illness or inabilities, thus allowing for motivational character to be
      established without committing to its implications, and without appearing
      strategic or biased. By contrast, professional parties in the meetings invoke the
      sick person's 'wants' either to hold them accountable, or for establishing a
      desired course of recovery, confirming the centrality of such 'wants' in this
      setting as well as the risks associated with expressing them. The article
      suggests that analysing psychological matters as they are oriented to by
      participants renders sick role theory relevant for a wide range of settings and
      respecifies criticism of the model.

PMID- 28503756
TI  - Biofilms and delayed healing - an in vitro evaluation of silver- and iodine
      containing dressings and their effect on bacterial and human cells.
AB  - This study investigated whether there are differences in the ability of wound
      dressings to modulate certain factors known to affect wound healing. A selection
      of antimicrobial dressings (AQUACEL(r) Ag ExtraTM , AQUACEL(r) Ag+ ExtraTM ,
      IODOFLEXTM , ACTICOATTM 7 and PROMOGRAN PRISMATM matrix) were tested for their
      effect on both bacterial bioburden and human dermal fibroblasts. Some dressings
      underwent further evaluation for activity against Pseudomonas aeruginosa biofilms
      using a colony-drip flow reactor model. The ability of in vitro biofilms to
      produce proteases, and the effect of PROMOGRAN PRISMA matrix on such proteases,
      was also investigated. All antimicrobial dressings tested reduced vegetative
      bacterial load; however, only PROMOGRAN PRISMA matrix was able to significantly
      reduce biofilm populations (P = 0.01). Additionally, PROMOGRAN PRISMA matrix was
      the only dressing that did not inhibit dermal fibroblast growth. All other
      dressings were detrimental to cell viability. In vitro biofilms of Pseudomonas
      aeruginosa were demonstrated as being capable of releasing bacterial proteases
      into their surroundings, and incubation with PROMOGRAN PRISMA matrix led to a 77%
      reduction in activity of such proteases (P = 0.002). The unique ability of
      PROMOGRAN PRISMA matrix to reduce in vitro vegetative bacteria, biofilm bacteria
      and bacterial proteases while still allowing dermal fibroblast proliferation may
      help rebalance the wound environment and reduce the occurrence of infection.

PMID- 28503757
TI  - Increase in minimal erythemal dose following oral administration of an
      antioxidant complex based on a mix of carotenoids: Double-blind, placebo
      controlled trial.

PMID- 28503758
TI  - Postnatal mandible growth in wild and laboratory mice: Differences revealed from
      bone remodeling patterns and geometric morphometrics.
AB  - Comparative information on the variation in the temporospatial patterning of
      mandible growth in wild and laboratory mice during early postnatal ontogeny is
      scarce but important to understand variation among wild rodent populations. Here,
      we compare mandible growth between two ontogenetic series from the second to the
      eighth week of postnatal life, corresponding to two different groups of mice
      reared under the same conditions: the classical inbred strain C57BL/6J, and Mus
      musculus domesticus. We characterize the ontogenetic patterns of bone remodeling
      of the mandibles belonging to these laboratory and wild mice by analyzing bone
      surface, as well as examine their ontogenetic form changes and bimodular
      organization using geometric morphometrics. Through ontogeny, the two mouse
      groups display similar directions of mandible growth, according to the
      temporospatial distribution of bone remodeling fields. The allometric shape
      variation of the mandibles of these mice entails the relative enlargement of the
      ascending ramus. The organization of the mandible into two modules is confirmed
      in both groups during the last postnatal weeks. However, especially after
      weaning, the mandibles of wild and laboratory mice differ in the timing and
      localization of several remodeling fields, in addition to exhibiting different
      patterns of shape variation and differences in size. The stimulation of dentary
      bone growth derived from the harder post-weaning diet might account for some
      features of postnatal mandible growth common to both groups. Nonetheless, a large
      component of the postnatal growth of the mouse mandible appears to be driven by
      the inherent genetic programs, which might explain between-group differences.

PMID- 28503759
TI  - Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular
      Osteosarcoma.
AB  - BACKGROUND: The prevalence of cancer cachexia in veterinary medicine has not been
      studied widely, and as of yet, no definitive diagnostic criteria effectively
      assess this syndrome in veterinary patients. OBJECTIVES: (1) To determine the
      patterns of weight change in dogs with appendicular osteosarcoma treated with
      amputation and single-agent carboplatin during the course of adjuvant
      chemotherapy; and (2) to determine whether postoperative weight change is a
      negative prognostic indicator for survival time in dogs with osteosarcoma.
      ANIMALS: Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were
      accrued from 3 veterinary teaching hospitals. METHODS: Retrospective, multi
      institutional study. Dogs diagnosed with appendicular osteosarcoma and treated
      with limb amputation followed by a minimum of 4 doses of single-agent carboplatin
      were included. Data analyzed in each patient included signalment, tumor site,
      preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at
      each carboplatin treatment. RESULTS: A slight increase in weight occurred over
      the course of chemotherapy, but this change was not statistically significant.
      Weight change did not have a significant effect on survival. Institution, patient
      sex, and serum ALP activity did not have a significant effect on survival.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Weight change was not a prognostic factor in
      these dogs, and weight loss alone may not be a suitable method of determining
      cancer cachexia in dogs with appendicular osteosarcoma.

PMID- 28503760
TI  - The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation
      carriers.
AB  - Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary
      paraganglioma (PGL) syndrome type 4. The risk of developing PGL or
      pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In
      the present nationwide cohort study of SDHB mutation carriers identified by the
      clinical genetics centers of the Netherlands, we have calculated the penetrance
      of SDHB associated tumors using a novel maximum likelihood estimator. This
      estimator addresses ascertainment bias and missing data on pedigree size and
      structure. A total of 195 SDHB mutation carriers were included, carrying 27
      different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder
      mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A
      mutation (24% of mutation carriers). One hundred and twelve carriers (57%)
      displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty
      four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26
      patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is
      estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for
      ascertainment. These estimates are lower than previously reported penetrance
      estimates of SDHB-linked cohorts. Similar disease risks are found for different
      SDHB germline mutations as well as for male and female SDHB mutation carriers.

PMID- 28503761
TI  - Diabetes among Maori women with self-reported past gestational diabetes mellitus
      in a New Zealand Maori community.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for subsequent
      development of type 2 diabetes mellitus (T2DM). We have investigated the extent
      of this risk among Maori women without known diabetes. MATERIALS AND METHODS: We
      recruited 2786 Maori women aged 28-86 years between 2004 and 2006, without
      diagnosed diabetes from the Waikato and Southern Lakes regions, via media,
      community and general practitioner channels, and invited them for an oral glucose
      tolerance test (OGTT). RESULTS: Fifty (1.8%) women reported previous GDM (pGDM).
      The prevalence decreased significantly with age (P = 0.009). Women aged <50 years
      with pGDM had higher body mass index (35.6 +/- 6.7 vs 32.4 +/- 7.7 kg/m2 , P <
      0.01), waist circumference (105.3 +/- 18.8 vs 96.9 +/- 16.6 cm, P < 0.01),
      fasting blood glucose (5.5 +/- 1.0 vs 5.1 +/- 0.8 mmol/L, P <= 0.01), two-hour
      post-prandial blood glucose (6.6 +/- 3.0 vs 5.6 +/- 2.1 mmol/L, P < 0.01) and
      HbA1c (6.0 +/- 0.8 vs 5.8 +/- 0.6%, P < 0.05) than women without pGDM. PGDM was a
      significant risk factor for undiagnosed diabetes (odds ratio 4.0; (5% confidence
      interval 1.67-9.71). Undiagnosed diabetes was significantly more prevalent among
      women with than without pGDM aged <40 years (20.0% vs 1.5%). CONCLUSION: Self
      reported past GDM was a significant risk factor for undiagnosed diabetes in this
      Maori population, particularly among women aged <40 years, highlighting the
      importance of targeting this group for more intensive screening.

PMID- 28503762
TI  - Contribution to the discussion of "A critical evaluation of the current 'p-value
      controversy'".

PMID- 28503763
TI  - Visible Light Induced Organic Transformations Using Metal-Organic-Frameworks
      (MOFs).
AB  - With the aim of developing renewable energy based processes, researchers are
      paying increasing interest to light induced organic transformations. Metal
      organic frameworks (MOFs), a class of micro-/mesoporous hybrid materials, are
      recently emerging as a new type of photoactive materials for organic syntheses
      due to their unique structural characteristics. In this Review, we summarized the
      recent applications of MOFs as photocatalysts for light induced organic
      transformations, including (1) oxidation of alcohols, amines, alkene, alkanes and
      sulfides; (2) hydroxylation of aromatic compounds like benzene; (3) activation of
      the C-H bonds to construct new C-C or C-X bonds; (4) atom-transfer radical
      polymerization (ATRP). This Review starts with general background information of
      using MOFs in photocatalysis, followed by a description of light induced organic
      transformations promoted by photoactive inorganic nodes and photocatalytic active
      ligands in MOFs, respectively. Thereafter, the use of MOFs as multifunctional
      catalysts for light induced organic transformations via an efficient merge of the
      metal/ligand/guest based catalysis where the photocatalytic activity of MOFs
      plays a key role are discussed. Finally, the limitations, challenges and the
      future perspective of the application of MOFs for light induced organic
      transformations were addressed. The objective of this Review is to serve as a
      starting point for other researchers to get into this largely unexplored field.
      It is also our goal to stimulate intensive research in this field for rational
      designing of MOF materials to overcome their current limitations in
      photocatalysis, which can lead to more creative visible-light-induced organic
      transformations.

PMID- 28503765
TI  - 57th Annual Teratology Society Meeting.

PMID- 28503764
TI  - Interpretation of Seemingly Contradictory Data: Low NMR S2 Order Parameters
      Observed in Helices and High NMR S2 Order Parameters in Disordered Loops of the
      Protein hGH at Low pH.
AB  - At low pH, human growth hormone (hGH) adopts a partially folded state, in which
      the native helices are maintained, but the long loop regions and side-chain
      packing become disordered. Some of the S2 order parameters for backbone N-H
      vectors derived from NMR relaxation measurements on hGH at low pH initially seem
      contradictory. Three isolated residues (15, 20, and 171) in helices A and D
      exhibit low order parameter values (<0.5) indicating flexibility, whereas residue
      143 in the centre of a long flexible loop region has a high order parameter
      (0.82). Using S2 order parameter restraining MD simulations, this paradox has
      been resolved. Low S2 values in helices are due to the presence of a mixture of
      310 -helical and alpha-helical hydrogen bonds. High S2 values in relatively
      disordered parts of a protein may be due to fluctuating networks of hydrogen
      bonds between the backbone and the side chains, which restrict the motion of N-H
      bond vectors.

PMID- 28503766
TI  - Editorial Comment to Pelvic floor muscle therapy or alpha-blocking agents for
      treatment of men with lower urinary tract symptoms: An exploratory randomized
      controlled trial.

PMID- 28503767
TI  - The world of epithelial sheets.
AB  - An epithelium is a layer of closely connected cells covering the body or lining a
      body cavity. In this review, several fundamental questions are addressed
      regarding the epithelium. (i) While an epithelium functions as barrier against
      the external environment, how is barrier function maintained during its
      construction? (ii) What determines the apical and basal sides of epithelial
      layer? (iii) Is there any relationship between the apical side of the epithelium
      and the apical membrane of an epithelial cell? (iv) Why are hepatocytes (liver
      cells) called epithelial, even though they differ completely from column-like
      shape of typical epithelial cells? Keeping these questions in mind, multiple
      shapes of epithelia were considered, extracting a few of their elemental
      processes, and constructing a virtual world of epithelia by combining them.
      Epithelial cells were also classified into several types based on the number of
      apical domains of each cell. In addition, an intracellular organelle was
      introduced within epithelial cells, the vacuolar apical compartment (VAC), which
      is produced within epithelial cells surrounded by external cell matrix (ECM). The
      VAC interacts with areas of cell-cell contact of the cell surface membrane and is
      converted to apical membrane. The properties of VACs enable us to answer the
      initial questions posed above. Finally, the genetic and molecular mechanisms of
      epithelial morphogenesis are discussed.

PMID- 28503768
TI  - Contribution of cardiometabolic risk factors to estimated glomerular filtration
      rate decline in Indigenous Australians with and without albuminuria - the eGFR
      Follow-up Study.
AB  - AIM: We assessed associations between cardiometabolic risk factors and estimated
      glomerular filtration rate (eGFR) decline according to baseline albuminuria to
      identify potential treatment targets in Indigenous Australians. METHODS: The eGFR
      Follow-up Study is a longitudinal cohort of 520 Indigenous Australians. Linear
      regression was used to estimate associations between baseline cardiometabolic
      risk factors and annual Chronic Kidney Disease Epidemiology Collaboration eGFR
      change (mL/min per 1.73m2 /year), among those classified with baseline
      normoalbuminuria (urine albumin-to-creatinine ratio (uACR) <3 mg/mmol; n = 297),
      microalbuminuria (uACR 3-30 mg/mmol; n = 114) and macroalbuminuria (uACR >=30
      mg/mmol; n = 109). RESULTS: After a median of 3 years follow-up, progressive
      declines of the age- and sex-adjusted mean eGFR were observed across albuminuria
      categories (-2.0 [-2.6 to -1.4], -2.5 [-3.7 to -1.3] and -6.3 [-7.8 to -4.9]
      mL/min per 1.72m2 /year). Although a borderline association was observed between
      greater baseline haemoglobin A1c and eGFR decline in those with macroalbuminuria
      (P = 0.059), relationships were not significant in those with microalbuminuria (P
      = 0.187) or normoalbuminuria (P = 0.23). Greater baseline blood pressure, C
      reactive protein, waist-to-hip ratio and lower high-density lipoprotein
      cholesterol showed non-significant trends with greater eGFR decline in the
      presence of albuminuria. CONCLUSION: Over a 3 year period, marked eGFR decline
      was observed with greater baseline albuminuria. Cardiometabolic risk factors were
      not strong predictors for eGFR decline in Indigenous Australians without
      albuminuria. Longer follow-up may elucidate the role of these predictors and
      other mechanisms in chronic kidney disease progression in this population.

PMID- 28503771
TI  - Editorial Comment from Dr Campobasso to Adult genitourinary sarcoma: Clinical
      characteristics and survival in a series of patients treated at a high-volume
      institution.

PMID- 28503770
TI  - Disposition of levetiracetam in healthy adult horses.
AB  - Nine horses received 20 mg/kg of intravenous (LEVIV ); 30 mg/kg of intragastric,
      crushed immediate release (LEVCIR ); and 30 mg/kg of intragastric, crushed
      extended release (LEVCER ) levetiracetam, in a three-way randomized crossover
      design. Crushed tablets were dissolved in water and administered by nasogastric
      tube. Serum samples were collected over 48 hr, and levetiracetam concentrations
      were determined by immunoassay. Mean +/- SD peak concentrations for LEVCIR and
      LEVCER were 50.72 +/- 10.60 and 53.58 +/- 15.94 MUg/ml, respectively. The y
      intercept for IV administration was 64.54 +/- 24.99 MUg/ml. The terminal half
      life was 6.38 +/- 1.97, 7.07 +/- 1.93 and 6.22 +/- 1.35 hr for LEVCIR , LEVCER,
      and LEVIV , respectively. Volume of distribution at steady-state was 630 +/- 73.4
      ml/kg. Total body clearance after IV administration was 74.40 +/- 19.20 ml kg-1 
      hr-1 . Bioavailability was 96 +/- 10, and 98 +/- 13% for LEVCIR and LEVCER ,
      respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on
      this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg
      every 12 hr is likely to achieve and maintain plasma concentrations within the
      therapeutic range suggested for humans, with optimal kinetics throughout the
      dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic
      studies are warranted.

PMID- 28503772
TI  - Refractory thoracic endometriosis syndrome with bilateral hemothorax.
AB  - Thoracic endometriosis syndrome (TES) is a rare disorder presenting with
      catamenial pneumothorax, hemothorax, hemoptysis or pulmonary nodules. Bilateral
      involvement is uncommon, and only a very few cases have been reported in the
      literature. We report a case of bilateral catamenial hemothorax in a patient with
      recurrent thoracic endometriosis. Despite multiple surgical interventions, the
      patient continued to develop hemopneumothorax coinciding with menses. Remission
      was finally achieved with the addition of gonadotropin-releasing hormone agonist,
      highlighting the effectiveness of postoperative adjuvant hormone therapy and
      supporting a combined surgical and medical approach in the treatment of TES in
      patients who desire future fertility.

PMID- 28503769
TI  - Identification of factors required for m6 A mRNA methylation in Arabidopsis
      reveals a role for the conserved E3 ubiquitin ligase HAKAI.
AB  - N6-adenosine methylation (m6 A) of mRNA is an essential process in most
      eukaryotes, but its role and the status of factors accompanying this modification
      are still poorly understood. Using combined methods of genetics, proteomics and
      RNA biochemistry, we identified a core set of mRNA m6 A writer proteins in
      Arabidopsis thaliana. The components required for m6 A in Arabidopsis included
      MTA, MTB, FIP37, VIRILIZER and the E3 ubiquitin ligase HAKAI. Downregulation of
      these proteins led to reduced relative m6 A levels and shared pleiotropic
      phenotypes, which included aberrant vascular formation in the root, indicating
      that correct m6 A methylation plays a role in developmental decisions during
      pattern formation. The conservation of these proteins amongst eukaryotes and the
      demonstration of a role in writing m6 A for the E3 ubiquitin ligase HAKAI is
      likely to be of considerable relevance beyond the plant sciences.

PMID- 28503773
TI  - The table grape 'Victoria' with a long shaped berry: a potential mutation with
      attractive characteristics for consumers.
AB  - BACKGROUND: Puglia is the most important region in Italy for table grape
      production. Since consumers look for new products, the number of table grape
      varieties has greatly increased in recent years. RESULTS: In a survey in the
      Puglia region, we identified several years ago a potential mutation of the cv.
      Victoria. We described this accession in comparison with the standard Victoria
      for some amphelographic traits. All the characteristics were very similar to the
      standard Victoria except for the berry shape, which was significantly more
      elongated. Moreover, the berry of the mutated Victoria showed higher firmness,
      lightness and chroma than the standard one, with a more intense yellow colour of
      the skin (appreciated by consumers). The molecular characterisation with 25 SSR
      markers showed that normal and mutant Victoria were genetically identical at all
      the analysed loci, thus suggesting that the two accessions could be considered as
      clones with the difference in berry shape probably due to a somatic mutation.
      CONCLUSIONS: This mutation of the cv. Victoria may have interesting perspective
      for the market since consumers are always attracted by different shape and colour
      of the fruits (consumers buy with eyes). This accession can be an alternative
      clone of the already known standard Victoria. (c) 2017 Society of Chemical
      Industry.

PMID- 28503774
TI  - Effect of the injectable contraceptive depot-medroxyprogesterone acetate on
      coagulation parameters in new users.
AB  - AIM: The aim of this study was to assess the effects of the injectable depot
      medroxyprogesterone acetate (DMPA) contraceptive on selected blood coagulation
      parameters in young, healthy new users. METHODS: The prospective study included
      39 healthy women aged 20-39 years, with a body mass index (BMI; kg/m2 ) < 30, who
      were never users of DMPA, and who opted to use DMPA (21 women) or a copper
      intrauterine device (IUD; 18 women). The women in the two groups were matched for
      age (+/-1 year) and BMI (+/-1). Blood samples were obtained from all participants
      at baseline and at 6 and 12 months. Activated partial thromboplastin time, D
      dimer, protein C, antithrombin, protein S, and thrombin generation test (lag
      time, endogenous thrombin potential, time to peak, and velocity index of thrombin
      generation) were analyzed. Repeated-measures analysis of variance was used to
      compare the groups. RESULTS: There were no significant differences between the
      groups at baseline with respect to any of the parameters evaluated; however, in
      the DMPA group, D-dimer levels were lower and the time to peak thrombin
      generation was longer than in the IUD group at 12 months of evaluation.
      CONCLUSION: Lower D-dimer and longer time to peak thrombin generation in new
      users of DMPA suggest a positive profile against hypercoagulability.

PMID- 28503775
TI  - Contemporary psychology and women: A gender analysis of the scientific
      production.
AB  - Despite important advances made in recent decades, women are still
      underrepresented in science (less than 30% of authorships). This study presents a
      bibliometric analysis of all the Psychology articles published in 2009 included
      in the Web of Science database (Thomson Reuters) in order to examine the
      contribution of women in contemporary Psychology, their pattern of research
      collaboration, the scientific content and the scientific impact from a gender
      perspective. From a total of 90,067 authorships, gender could be identified in
      74,413 (82.6%) of them, being 40,782 (54.8%) male authorships and 33,631 (45.2%)
      female authorships. These data corresponded to 24,477 (49.9%) individual men and
      24,553 (50.1%) women, respectively. Therefore, Psychology presents gender parity
      in the number of authors, and a gender asymmetry in the number of authorships
      that it is much lower than in science in general and other specific scientific
      fields. In relative terms, women tend to be concentrated in the first position of
      the authorship by-line and much less in the last (senior) position. This double
      pattern suggests that age probably plays a role in (partly) explaining the slight
      gender disparity of authorships.

PMID- 28503776
TI  - Differences in dietary and lifestyle habits between pregnant women with small
      fetuses and appropriate-for-gestational-age fetuses.
AB  - AIM: The purpose of this study was to determine differences in lifestyle and
      dietary habits between pregnant women with small for gestational age (SGA)
      fetuses and those appropriate for gestational age (AGA). METHODS: This cross
      sectional, prospective study was conducted over 14 months and included 46 mothers
      with SGA and 81 with AGA fetuses. Fetal growth was assessed by a routine third
      trimester scan. Participants completed questionnaires regarding dietary habits,
      lifestyle behavior and sociodemographic characteristics during the third
      trimester. RESULTS: Mothers maintaining a Mediterranean-type diet and lifestyle
      were more likely to have an AGA fetus (P < 0.05). The same number of women in
      both groups ate a vegetarian diet. Women in the SGA group had a lower intake of
      certain micronutrients: carotene, folic acid, iron, potassium and magnesium (P <
      0.05). Women in the AGA group ate more vegetables, especially green beans,
      carrots, lettuce and oranges (P < 0.05). Bread, pasta, cakes and jam were also
      more frequently consumed by the AGA group (P < 0.05). Mothers in the SGA group
      drank more cola (P < 0.05), while mothers in the AGA group drank more diet cola
      and wine (P < 0.05). Women in the SGA group smoked more cigarettes per day (P <
      0.05). CONCLUSIONS: Mothers of SGA fetuses had a different nutritional intake and
      cigarette smoking habits compared with mothers of AGA fetuses. No other
      differentiating lifestyle habits were observed between the groups. Thus,
      intrauterine growth conditions might be improved by the endorsement of certain
      dietary habits during pregnancy.

PMID- 28503777
TI  - Determination of threshold concentrations of plant pollens in intradermal testing
      using fluorescein in clinically healthy nonallergic cats.
AB  - BACKGROUND: Currently the same allergen concentrations for canine intradermal
      testing (IDT) are recommended for feline IDT. Feline skin reactions are subtle
      and more difficult to read than canine reactions. This difference may be due to
      suboptimal allergen concentrations used for IDT in cats. HYPOTHESIS/OBJECTIVES:
      To determine the irritant threshold concentration (ITC) of 16 pollen allergens
      using serial dilutions of allergen and intravenous fluorescein. The hypothesis
      tested was that feline IDT currently is performed at suboptimal allergen
      concentrations for pollens. ANIMALS: Twenty privately owned healthy clinically
      nonallergic cats. METHODS: IDT was performed in duplicate using 16 pollen
      allergens (weeds, grasses and trees) at a dilution of 8000 PNU/mL. Two blinded
      investigators graded the test reactions independently using subjective and
      objective criteria. Intravenous fluorescein was then administered and the test
      reactions were re-evaluated. IDT was repeated for any allergen that was positive,
      using serial dilutions of allergen at a concentration of 6000 and 4000 PNU/mL.
      RESULTS: The ITC for 2 of 16 of the allergens was determined. The ITC of Cynodon
      dactylon (Bermuda grass) and Schinus spp. (Peppercorn) was determined to be
      between 6000 and 8000 PNU/mL. The ITC of all other allergens tested in this study
      was >8000 PNU/mL. CONCLUSIONS AND CLINICAL IMPORTANCE: This study confirms that
      suboptimal allergen concentrations currently are used for feline IDT as the ITC
      is >8000 PNU/mL for 14 of 16 of the grass, weed and tree pollens evaluated. The
      ITC of Cynodon dactylon and Schinus spp. was determined to be between 6000 and
      8000 PNU/mL.

PMID- 28503779
TI  - Normal amniotic fluid volume across gestation: Comparison of statistical
      approaches in 1190 normal amniotic fluid volumes.
AB  - AIM: Ultrasound estimation and evaluation of amniotic fluid volume (AFV) is an
      important component of pregnancy surveillance and fetal well-being. The purpose
      of this study was to compare and contrast four statistical methods used to
      construct gestational age-specific reference intervals for the assessment of AFV.
      METHODS: A total of 1095 normal AFV derived from four studies that measured AFV
      using dye-dilution or direct measurement at the time of hysterotomy were used to
      construct reference intervals using polynomial regression, quantile regression,
      Royston and Wright mean and SD, and Cole's lambda mu sigma (LMS) methods. The
      2.5th, 5th, 50th, 95th, and 97.5th centiles were derived for each statistical
      method. RESULTS: AFV increased curvilinearly from 15 gestational weeks and
      onward. Based on the 50th centile, the maximum value occurred at 30 weeks'
      gestation for the polynomial regression and mean and SD methods while the maximum
      was achieved at week 31 for the quantile regression and LMS methods. When data
      were sparse, the quantile regression method produced dramatically different
      estimates at the higher centile. CONCLUSION: The four statistical methods
      produced similar results at gestational ages in which AFV was high. The quantile
      regression approach, however, produces results that are more reflective of the
      data when the data are sparse. Given the flexibility and robustness of the
      quantile regression method, we recommend its use in constructing reference
      intervals when the interest lies in the tails of the reference distribution.

PMID- 28503780
TI  - A Case of a Chorionic Bump: New Sonographic-Histopathologic Findings With Review
      of the Literature.

PMID- 28503778
TI  - A Topical Zinc Ionophore Blocks Tumorigenic Progression in UV-exposed SKH-1 High
      risk Mouse Skin.
AB  - Nonmelanoma skin cancer (NMSC) is the most common malignancy in the United States
      representing a considerable public health burden. Pharmacological suppression of
      skin photocarcinogenesis has shown promise in preclinical and clinical studies,
      but more efficacious photochemopreventive agents are needed. Here, we tested
      feasibility of harnessing pharmacological disruption of intracellular zinc
      homeostasis for photochemoprevention in vitro and in vivo. Employing the zinc
      ionophore and FDA-approved microbicidal agent zinc pyrithione (ZnPT), used
      worldwide in over-the-counter (OTC) topical consumer products, we first
      demonstrated feasibility of achieving ZnPT-based intracellular Zn2+ overload in
      cultured malignant keratinocytes (HaCaT-ras II-4; SCC-25) employing membrane
      permeable fluorescent probes. Zinc overload was accompanied by induction of
      intracellular oxidative stress, associated with mitochondrial superoxide release
      as substantiated by MitoSOX RedTM fluorescence microscopy. ZnPT-induced cell
      death observable in malignant keratinocytes was preceded by induction of metal
      (MT2A), proteotoxic (HSPA6, HSPA1A, DDIT3, HMOX1) and genotoxic stress response
      (GADD45A, XRCC2) gene expression at the mRNA and protein levels. Comet analysis
      revealed introduction of formamidopyrimidine-DNA glycosylase (Fpg)-sensitive
      oxidative DNA lesions. In a photocarcinogenesis model (UV-exposed SKH-1 high-risk
      mouse skin), topical ZnPT administration post-UV caused epidermal zinc overload
      and stress response gene expression with pronounced blockade of tumorigenesis.
      Taken together, these data suggest feasibility of repurposing a topical OTC drug
      for zinc-directed photochemoprevention of solar UV-induced NMSC.

PMID- 28503782
TI  - Quantification of root water uptake in soil using X-ray computed tomography and
      image-based modelling.
AB  - Spatially averaged models of root-soil interactions are often used to calculate
      plant water uptake. Using a combination of X-ray computed tomography (CT) and
      image-based modelling, we tested the accuracy of this spatial averaging by
      directly calculating plant water uptake for young wheat plants in two soil types.
      The root system was imaged using X-ray CT at 2, 4, 6, 8 and 12 d after
      transplanting. The roots were segmented using semi-automated root tracking for
      speed and reproducibility. The segmented geometries were converted to a mesh
      suitable for the numerical solution of Richards' equation. Richards' equation was
      parameterized using existing pore scale studies of soil hydraulic properties in
      the rhizosphere of wheat plants. Image-based modelling allows the spatial
      distribution of water around the root to be visualized and the fluxes into the
      root to be calculated. By comparing the results obtained through image-based
      modelling to spatially averaged models, the impact of root architecture and
      geometry in water uptake was quantified. We observed that the spatially averaged
      models performed well in comparison to the image-based models with <2% difference
      in uptake. However, the spatial averaging loses important information regarding
      the spatial distribution of water near the root system.

PMID- 28503783
TI  - Clinical and radiological features of an unusual fungal infection of shoulder.

PMID- 28503781
TI  - Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and
      high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib.
AB  - AIMS: Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being
      developed for treatment of auto-immune inflammatory disorders. This work
      evaluated effects of high-fat meal, cytochrome P450 (CYP) 3A inhibition, CYP
      induction, and organic anion transporting polypeptide (OATP) 1B inhibition on
      upadacitinib pharmacokinetics. METHODS: Two Phase 1 evaluations were conducted,
      each in 12 healthy subjects. In Study 1, using a randomized, two-sequence
      crossover design, a 3 mg dose of upadacitinib (immediate-release capsules) was
      administered alone under fasting conditions, after high-fat meal, or on Day 4 of
      a 6-day regimen of 400 mg once-daily ketoconazole. In Study 2, a 12 mg
      upadacitinib dose was administered alone, with the first, and with the eighth
      dose of a 9-day regimen of rifampin 600 mg once daily. Upadacitinib plasma
      concentrations were characterized. RESULTS: Administration of upadacitinib
      immediate-release capsules after a high-fat meal decreased upadacitinib Cmax by
      23% and had no impact on upadacitinib AUC relative to the fasting conditions.
      Ketoconazole (strong CYP3A inhibitor) increased upadacitinib Cmax and AUC by 70%
      and 75%, respectively. Multiple doses of rifampin (broad CYP inducer) decreased
      upadacitinib Cmax and AUC by approximately 50% and 60%, respectively. A single
      dose of rifampin (also an OATP1B inhibitor) had no effect on upadacitinib AUC.
      Upadacitinib was well tolerated when co-administered with ketoconazole, rifampin,
      or after a high-fat meal. CONCLUSIONS: Strong CYP3A inhibition and broad CYP
      induction result in a weak and moderate effect, respectively, on upadacitinib
      exposures. OATP1B inhibition and administration of upadacitinib immediate-release
      formulation with food does not impact upadacitinib exposure.

PMID- 28503784
TI  - Aryl hydrocarbon receptor and unexplained miscarriage.
AB  - AIM: The aim of this study was to carry out a preliminary investigation of the
      expression of aryl hydrocarbon receptor (AhR) in decidua and villus and the
      relationship between AhR and unexplained miscarriage. METHODS: The expression of
      AhR mRNA and protein from decidua and villus were measured using real-time
      reverse transcription-polymerase chain reaction, western blot and
      immunohistochemistry in 34 patients with unexplained miscarriage (miscarriage
      group) and 38 women with normal early pregnancy (control group). RESULTS: The AhR
      mRNA and protein expression was increased significantly in the villus in both
      groups compared with decidua (P < 0.05, P < 0.05). In decidua, AhR mRNA and
      protein expression in the miscarriage group was increased significantly compared
      with the control group (P < 0.05, P < 0.05). In villus, AhR mRNA and protein
      expression in the miscarriage group was increased significantly compared with the
      control group (P < 0.05, P < 0.05). AhR is expressed mostly in the cytoplasm of
      syncytiotrophoblasts in villus, and also in the cytoplasm of decidual cells.
      CONCLUSIONS: AhR was expressed more in the villus than in the decidua, and the
      upregulation of AhR mRNA and protein expression is associated with the
      pathogenesis of unexplained miscarriage.

PMID- 28503785
TI  - Novel Technique for Measurement of Fetal Right Myocardial Performance Index Using
      Dual Gate Pulsed-Wave Doppler.
AB  - OBJECTIVES: To evaluate the reproducibility of the fetal right myocardial
      performance index determined by simultaneous recording of inflow and outflow
      using a dual gate pulsed-wave Doppler (DD). METHODS: This was a prospective study
      of 39 normal singleton fetuses. Two experienced operators each measured the right
      myocardial performance index in three ways, twice: (1) separate recording of the
      inflow and outflow using single-gate pulsed-wave Doppler (PD), (2) simultaneous
      recordings of the inflow and outflow using tissue Doppler (TD), and (3)
      simultaneous recordings of the inflow and outflow using DD. Intra- and
      interoperator reproducibility were assessed with intraclass correlation
      coefficients. The measurements from all three methods taken by the more
      experienced operator were compared using Bland-Altman plots and mean differences.
      RESULTS: For both operators, intra-operator reproducibility was the highest when
      using DD, followed by PD, and TD. Interoperator agreement was the highest for PD
      measurements, followed by DD, and TD. The smallest mean difference was between
      the PD and DD measurements by the more experienced operator. There was a positive
      correlation between PD and DD values (r = 0.369, P < .001). CONCLUSIONS: Dual
      gate pulsed-wave Doppler may be an effective alternative to the PD or TD methods,
      and can separately evaluate systolic and diastolic myocardial function.

PMID- 28503787
TI  - Left lobe of liver in a Morgagni's hernia.

PMID- 28503786
TI  - Use of fluorescent in-situ hybridisation in salivary gland cytology: A powerful
      diagnostic tool.
AB  - OBJECTIVE: Salivary gland cytology is challenging because it includes a diversity
      of lesions and a wide spectra of tumours. Recently, it has been reported that
      many types of salivary gland tumours have specific molecular diagnostic
      signatures that could be identified by fluorescent in-situ hybridisation (FISH).
      The aim of the present study was to demonstrate the feasibility and efficiency of
      FISH on routine cytological salivary gland smears. METHODS: FISH was conducted on
      37 cytological salivary gland smears from 34 patients. According to the
      cytological diagnosis suspected, MECT1/MAML2 gene fusion and rearrangements of
      PLAG1, MYB, or ETV6 were analysed. The presence and percentages of cells that had
      gene rearrangements were evaluated. Results were compared with the histological
      surgical samples, available from 26 patients. RESULTS: The PLAG1 rearrangement
      was observed in 12/20 (60%) cases of pleomorphic adenoma. MECT1/MAML2 gene fusion
      was observed in 1:2 mucoepidermoid carcinomas but was not observed in five other
      tumours (two pleomorphic adenomas, one Warthin's tumour, one mammary analogue
      secretory carcinoma [MASC] and one cystic tumour). MYB rearrangement was observed
      in 4/4 adenoid cystic carcinomas. ETV6-gene splitting identified one MASC.
      CONCLUSION: Overall, FISH had a specificity of 100% and a sensitivity of 66.7%.
      When FISH and cytological analyses were combined, the overall sensitivity was
      increased to 93.3%. It can thus be concluded that when the FISH analysis is
      positive, the extent of surgery could be determined with confidence pre
      operatively without needing a diagnosis from a frozen section.

PMID- 28503788
TI  - Indicators of inappropriate tumour marker use through the mining of electronic
      health records.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Although the issue of monitoring appropriateness
      of tumour markers (TMs) request in outpatients remains crucial, proper indicators
      are still demanding. The present study developed and explored indicators of
      inappropriate TM ordering in outpatients through the data mining of electronic
      health records (EHRs). METHODS: Carcinoembryonic antigen (CEA), alfa-fetoprotein
      (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific
      antigen (PSA) ordered in outpatients during a year were examined by mining EHRs
      of a Local Health Authority in Italy. Evidence-based criteria were used to
      develop performance indicators. Demographic and clinical information associated
      with TM orders were examined. RESULTS: A total of 80 813 TMs were ordered in 52
      536 outpatients (1.54 markers/patient). Indicators related to disease codes,
      gender, age, and TM repetitions were developed, and their application showed that
      (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and
      65.6%) whereas the other TMs are largely requested also in patients without
      cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are
      negligible; (3) although requests in people older than 80 years are relevant
      (16.4% of total), the highest rate of request of all markers occurs in patients
      aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases
      between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69
      years; (5) <50% of PSA orders are associated with cancer code for all age
      intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA
      are prevalent in cancer patients or benign diseases to which TMs are appropriate,
      whereas PSA repetitions occur mainly in patients without cancer. CONCLUSIONS: The
      developed indicators resulted suitable to monitor TM overordering in outpatients
      through the mining of EHRs. The present study is a first approach towards the use
      of big-data mining for TM appropriateness evaluation purposes.

PMID- 28503789
TI  - Exploring the Structural Space of the Galectin-1-Ligand Interaction.
AB  - Galectin-1 is a tumor-associated protein recognizing the Galbeta1-4GlcNAc motif
      of cell-surface glycoconjugates. Herein, we report the stepwise expansion of a
      multifunctional natural scaffold based on N-acetyllactosamine (LacNAc). We
      obtained a LacNAc mimetic equipped with an alkynyl function on the 3'-hydroxy
      group of the disaccharide facing towards a binding pocket adjacent to the
      carbohydrate-recognition domain. It served as an anchor motif for further
      expansion by the Sharpless-Huisgen-Meldal reaction, which resulted in ligands
      with a binding mode almost identical to that of the natural carbohydrate
      template. X-ray crystallography provided a structural understanding of the
      galectin-1-ligand interactions. The results of this study enable the development
      of bespoke ligands for members of the galectin target family.

PMID- 28503790
TI  - Proton gradients at the origin of life.
AB  - Chemiosmotic coupling - the harnessing of electrochemical ion gradients across
      membranes to drive metabolism - is as universally conserved as the genetic code.
      As argued previously in these pages, such deep conservation suggests that ion
      gradients arose early in evolution, and might have played a role in the origin of
      life. Alkaline hydrothermal vents harbour pH gradients of similar polarity and
      magnitude to those employed by modern cells, one of many properties that make
      them attractive models for life's origin. Their congruence with the physiology of
      anaerobic autotrophs that use the acetyl CoA pathway to fix CO2 gives the
      alkaline vent model broad appeal to biologists. Recently, however, a paper by Baz
      Jackson criticized the hypothesis, concluding that natural pH gradients were
      unlikely to have played any role in the origin of life. Unfortunately, Jackson
      mainly criticized his own interpretations of the theory, not what the literature
      says. This counterpoint is intended to set the record straight.

PMID- 28503793
TI  - Rectus Abdominis Rhabdomyolysis: Report of 2 Cases.
AB  - Exercise-induced rhabdomyolysis is an unusual clinical entity for physicians and
      one that is frequently misdiagnosed. With the ever-increasing use of sonography
      by radiologists, sonographers, and sports physicians in the diagnosis of acute
      muscle injury, recognition of the typical sonographic appearance of
      rhabdomyolysis is paramount. Current literature using high-resolution ultrasound
      equipment is limited, with much of the literature offering dated or incongruent
      descriptions. We describe the sonographic findings of hyperechoic muscle and a
      hypoechoic halo of edema in 2 proven cases of rectus abdominis rhabdomyolysis
      after exercise.

PMID- 28503791
TI  - Blood Glucose and Insulin Concentrations after Octreotide Administration in
      Horses With Insulin Dysregulation.
AB  - BACKGROUND: Octreotide is a somatostatin analog that suppresses insulin
      secretion. HYPOTHESIS: We hypothesized that octreotide would suppress insulin
      concentrations in horses and that normal (N) horses and those with insulin
      dysregulation (ID) would differ significantly in their plasma glucose and insulin
      responses to administration of octreotide. ANIMALS: Twelve horses, N = 5, ID = 7.
      METHODS: Prospective study. An oral sugar test was performed to assign horses to
      N and ID groups. Octreotide (1.0 MUg/kg IV) was then administered, and blood was
      collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6,
      8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area
      under the curve (AUC) values were calculated. RESULTS: Mean AUC values for
      glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups
      after octreotide injection. Significant time (P < .001) effects were detected for
      glucose and insulin concentrations. A group * time interaction (P = .091) was
      detected for insulin concentrations after administration of octreotide, but the
      group (P = .33) effect was not significant. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then
      concentrations increase above baseline as glycemic control is restored. Our
      hypothesis that octreotide causes insulin concentrations to decrease in horses
      was supported, but differences between N and ID groups did not reach statistical
      significance when blood glucose and insulin responses were compared. The utility
      of an octreotide response test remains to be determined.

PMID- 28503792
TI  - Synthetic cannabinoid use in an acute psychiatric inpatient unit.
AB  - In the present study, we explored the prevalence of new psychoactive substance
      use by people admitted into an Australian acute public mental health facility
      specializing in comorbid mental health and substance use. These substances have
      since been banned from retail outlets, but the pattern of uptake and reasons
      people use them is informative in terms of motivations and the management of
      substance use more generally. A cross-sectional study to explore the use of
      synthetic cannabis by people admitted to an acute adult mental health unit was
      undertaken. Associations with diagnostic, service use, and demographic profiles
      were explored. Fifty-six percent of people reported having used at least one type
      of new psychoactive substance, including 53.5% who reported using synthetic
      cannabis alone, and 18.8% who reported using both synthetic cannabis and other
      new psychoactive substances. Synthetic cannabis use was not associated with any
      demographic or diagnostic groups. Legality and availability (43% combined) were
      common reasons for use, along with the feeling of intoxication (20%). The high
      prevalence of new psychoactive substance use adds weight to the recommendation
      that clinicians should routinely screen for substances from the time of
      admission. Accurate information about these substances is required in order to
      provide accurate guidance and appropriate interventions to people in their care.

PMID- 28503794
TI  - Estimated glomerular filtration rate on postoperative day 1 is associated with
      renal functional outcome after percutaneous renal cryoablation for renal tumors.

PMID- 28503796
TI  - Influence of an intentionally induced posterior lens capsule rupture on the real
      time intraocular pressure during phacoemulsification in canine ex vivo eyes.
AB  - OBJECTIVE: To evaluate the changes in the intraocular pressure (IOP) following an
      intentionally induced posterior lens capsule rupture (PLCR) during
      phacoemulsification in enucleated canine eyes. Furthermore, to compare the IOPs
      between different stages of phacoemulsification for two different bottle heights
      (BH). PROCEDURES: Coaxial phacoemulsification was performed using a venturi-based
      machine at a 60 or 90 cm BH. A pressure transducer, inserted into the anterior
      chamber through the peripheral cornea, monitored real-time IOP. For one half of
      the lens, the sculpt-segment removal (SS) was followed by irrigation/aspiration
      (IA). The PLCR was intentionally created, and the SS and IA were repeated on the
      residual lens fragments. RESULTS: For the 60 cm BH, the mean IOP following the
      PLCR was significantly higher than before the PLCR during SS (28.30 +/- 12.56 and
      38.71 +/- 9.43 mmHg before and after PLCR, respectively) and IA (42.76 +/- 12.46
      and 47.88 +/- 7.10 mmHg before and after PLCR, respectively) stages (P < 0.001).
      For the 90 cm BH, the mean IOP following the PLCR was also significantly higher
      than before the PLCR during SS (33.39 +/- 11.09 and 58.17 +/- 6.89 mmHg before
      and after PLCR, respectively) and IA (62.39 +/- 12.46 and 72.04 +/- 8.59 mmHg
      before and after PLCR, respectively) stages (P < 0.001). CONCLUSIONS: The
      occurrence of a PLCR led to an increase in IOP during both the SS and IA stages.
      The elevated IOP after the PLCR might be one of the most important factors for
      ocular tissue damage, as it reduces ocular perfusion. Additionally, the BH should
      be reduced following PLCR to prevent complications stemming from the raised IOP.

PMID- 28503795
TI  - Automatic detection of paroxysmal atrial fibrillation in patients with ischaemic
      stroke: better than routine diagnostic workup?
AB  - BACKGROUND AND PURPOSE: Prolonged electrocardiogram (ECG) monitoring after
      ischaemic stroke increases the diagnostic yield of paroxysmal atrial fibrillation
      (pAF). In order to facilitate the additional workload involved in ECG analysis
      due to prolonged monitoring times, we investigated the effectiveness of pAF
      detection with an automated software algorithm (SA) in comparison to the routine
      staff-based analysis (RA) during standard stroke-unit care. Therefore, patients
      with acute ischaemic stroke or transitory ischaemic attack presenting with sinus
      rhythmus on the admission ECG and no history of atrial fibrillation were
      prospectively included. METHODS: A 24-h Holter ECG assessment was performed using
      either RA based on a computer-aided evaluation and subsequent review by a
      cardiologist or a commercially available automated SA. In the case of discordant
      results concerning the occurrence of pAF between the two methods, the data
      underwent an independent external rating. RESULTS: Of 809 prospectively enrolled
      patients, 580 patients fulfilled the inclusion criteria. pAF was ultimately
      diagnosed in 3.3% of the cohort (19 patients). SA and RA correctly diagnosed pAF
      in 17 patients resulting in a comparable diagnostic effectiveness of the analysis
      methods (sensitivity: SA 89.5% vs. RA 89.5%; specificity: SA 99.3% vs. RA 99.1%;
      kappa, 0.686; P < 0.001; 95% confidence interval, 0.525-0.847). RA revealed
      clinically relevant ECG abnormalities in an additional seven patients.
      CONCLUSIONS: Although it should not completely replace RA, SA-based evaluation of
      Holter ECG reaches a high diagnostic effectiveness for the detection of pAF and
      can be used for a rapid and resource-saving analysis of ECG data to deal with
      prolonged monitoring times.

PMID- 28503797
TI  - The Nanomechanics of Lipid Multibilayer Stacks Exhibits Complex Dynamics.
AB  - The nanomechanics of lipid membranes regulates a large number of cellular
      functions. However, the molecular mechanisms underlying the plastic rupture of
      individual bilayers remain elusive. This study uses force clamp spectroscopy to
      capture the force-dependent dynamics of membrane failure on a model
      diphytanoylphosphatidylcholine multilayer stack, which is devoid of surface
      effects. The obtained kinetic measurements demonstrate that the rupture of an
      individual lipid bilayer, occurring in the bilayer parallel plane, is a
      stochastic process that follows a log-normal distribution, compatible with a pore
      formation mechanism. Furthermore, the vertical individual force-clamp
      trajectories, occurring in the bilayer orthogonal bilayer plane, reveal that
      rupturing process occurs through distinct intermediate mechanical transition
      states that can be ascribed to the fine chemical composition of the hydrated
      phospholipid moiety. Altogether, these results provide a first description of
      unanticipated complexity in the energy landscape governing the mechanically
      induced bilayer rupture process.

PMID- 28503798
TI  - Neutral and alkaline cellulases: Production, engineering, and applications.
AB  - Neutral and alkaline cellulases from microorganisms constitute a major group of
      the industrial enzymes and find applications in various industries. Screening is
      the important ways to get novel cellulases. Most fungal cellulases have acidic pH
      optima, except some fungi like Humicola insolens species. However, new
      applications require the use of neutral and alkaline cellulases in food, brewery
      and wine, animal feed, textile and laundry, pulp and paper industries,
      agriculture as well in scientific research purposes. Indeed, the demand for these
      enzymes is growing more rapidly than ever before, and becomes the driving force
      for research on engineering the cellulolytic enzymes. Here, we present an
      overview of the biotechnological research for neutral and alkaline cellulases.

PMID- 28503799
TI  - Lymph node dissection for Siewert II esophagogastric junction adenocarcinoma: a
      retrospective study of 136 cases.
AB  - BACKGROUND: To compare the lymph node dissection with the right transthoracic
      Ivor-Lewis (IL) procedure to that with the left transthoracic (LT) approach for
      Siewert type II adenocarcinoma of the esophagogastric (AEG) junction. METHODS: In
      this study, 136 patients with Siewert type II AEG who met the inclusion criteria
      underwent surgical resection were divided into the IL (47 cases) and LT (89
      cases) groups. The number and frequency of the dissected lymph nodes in each
      station were compared between the two groups. RESULTS: The IL group had a longer
      proximal surgical margin (P = 0.000) and more total (P = 0.000), thoracic (P =
      0.000), and abdominal lymph nodes (P = 0.000) dissected than the LT group. In
      general, the IL group had a higher dissection rate in each thoracic lymph node
      station (P < 0.05) than the LT group. The dissection rates of the hepatic artery,
      splenic artery and celiac trunk lymph nodes were higher in the IL group than in
      the LT group (P < 0.05). The lymph node metastasis rate was 78.7% in the IL
      group, higher than the 61.8% in the LT group (P = 0.045). CONCLUSIONS: The right
      transthoracic IL procedure was demonstrated to be a better application than the
      LT approach for Siewert type II AEG in terms of the number and frequency of lymph
      node resections.

PMID- 28503800
TI  - Secular trends in Australian school children's sleep and perceived importance of
      sleep between 1985 and 2013.
AB  - AIM: To examine secular trends in Australian children's actual sleep time as well
      as the perceived importance of sleep between 1985, 2004 and 2013. METHODS:
      Secular trends in children's sleep and their perception of the importance of
      sleep across three time points 1985 (N = 401), 2004 (N = 450) and 2013 (N = 395)
      were examined according to socio-economic status (SES), age and sex. The children
      self-reported their bedtime, wake-up time and their perceived importance of
      sleep, among other questions. RESULTS: There were no significant differences in
      sleep duration between boys and girls in any of the survey years, nor were there
      differences in sleep duration between SES categories at any time point.
      Independent of survey year, age, sex and SES, there was a graded difference in
      sleep duration (minutes) across response categories for perceived importance of
      sleep. Overall, trends in the perceived importance of sleep appeared to match
      trends in actual sleep time, but not for all subgroups. CONCLUSION: This study
      indicates that the sleep duration of high SES Australian school children is
      returning to, or near to, baseline sleep duration observed in 1985, while the
      sleep duration of low SES Australian children has remained at low levels.

PMID- 28503802
TI  - Electrospun polyethersolfone nanofibrous membrane as novel platform for protein
      immobilization in microfluidic systems.
AB  - In the present study, the feasibility of electrospun polyethersolfone (PES)
      nanofibrous membrane as the solid substrate for microfluidic based immunoassays
      to enhance the density of immobilized antibody on the surface of membrane was
      assessed. Conversely, the efficacy of antibody immobilization was compared by two
      different strategies as 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N
      Hydroxysuccinimide (NHS) coupling chemistry and hydrophobic interaction. Compared
      to conventional immunoassays carried out in plates or gels, microfluidic based
      immunoassays grant a lot of advantages such as a consumption of little samples
      and reagents, shorter analysis time, and higher efficiency. Therefore,
      microfluidic immunoassays can be efficiently used as a point-of-care device in
      medical diagnosis. Surprisingly, we found the increase of specific surface areas
      of the microfluidic channels improve density of immobilized proteins and leads to
      higher signal strength. Anti-staphylococcus enterotoxin B (anti-SEB) was used as
      an analyte model to demonstrate the utility of our proposed platform. Fluorescent
      microscopy, Fourier transform infrared spectroscopic (FTIR), gas adsorption,
      contact angle, X-ray photoelectron spectroscopy (XPS), scanning electron
      microscopy (SEM), Uv-Vis spectrophotometer and atomic force microscopy (AFM)
      techniques were used to assess the efficacy of antibody immobilization on the
      surface. To understand dominant mechanism of protein immobilization, zeta
      potential measurement was also carried out and it was found electrostatic
      attraction play significant role in antibody immobilization running into micro-
      channels containing through EDC/NHS. Moreover, incorporation of nanofibrous
      membrane causes significant improvement in the signal detection of microfluidic
      based immunoassay. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 106B: 1108-1120, 2018.

PMID- 28503801
TI  - Pioppino mushroom in southern Italy: an undervalued source of nutrients and
      bioactive compounds.
AB  - BACKGROUND: Agrocybe aegerita (V. Brig.) Singer, commonly known as Pioppino, is a
      popular edible mushroom, known in the Campania Region (Italy). Despite its
      habitual consumption, little nutritional and biochemical information is
      available. Thus, nutritional values, anti-radical properties and chemical
      composition of the wild Pioppino were compared to those of the cultivated
      Agaricus bisporus (J.E. Lange) Imbach (known as Champignon), equally analysed.
      RESULTS: Macronutrient components (proteins, carbohydrates and lipids), free and
      protein amino acids and fatty acid content of poplar mushroom were achieved.
      Total phenol content of a defatted Pioppino alcoholic extract (PM) was
      determined, whereas DPPH and ABTS methods were applied to determine the radical
      scavenging capabilities of the extract. Ferricyanide and ORAC-fluorescein methods
      were also performed. Finally, LC-HRMS was used to identify and quantify the main
      metabolites in the extract. PM was mainly constituted of disaccharides, hexitol
      derivatives and malic acid. Coumaric acid isomers and C6 C1 compounds were also
      detected. CONCLUSION: All data revealed that wild Pioppino is an excellent
      functional food, by far exceeding that of the Champignon. Therefore, these data
      are useful to promote the consumption of this mushroom encouraging thus its
      biological cultivation, due to wild availability is strongly compromised by the
      extensive use of fungicides. (c) 2017 Society of Chemical Industry.

PMID- 28503803
TI  - A microstructural study of the pleon-holding mechanism in Carcinus maenas
      (Decapoda, Brachyura, Portunoidea, Carcinidae) of different sizes.
AB  - Within the Brachyura there are a variety of specialized holding mechanisms, which
      facilitate the close attachment of the highly reduced pleon underneath the
      cephalothorax. The most common mechanism in eubrachyurans, known as the press
      button, consists of a sternal protrusion and a corresponding pleonal socket.
      Reports on the microstructural properties of the surface of these holding
      structures are scarce and patchy. In this study, the European Green Crab Carcinus
      maenas, is used as model to describe the microstructure of a typical press-button
      mechanism with the use of scanning electron microscopy and light microscopic
      histology. A highly tuberculate cuticle and an apical ridge on the sternal knob
      are found in juveniles of both sexes. The microstructures are lost in adult
      males. In adult females, the holding structures themselves are reduced, but never
      completely lost. These findings show that C. maenas does not undergo a single
      "final puberty moult," after which all juvenile characteristics are lost, as
      previously assumed. Further comparison of the morphology of juveniles to another
      species indicates a close resemblance of the holding structures at this stage.
      Therefore, the use of the microstructure of the pleon-holding mechanism for
      phylogenetic analysis is restricted to adult specimens.

PMID- 28503804
TI  - Neural correlates of visuomotor adjustments during scaling of human finger
      movements.
AB  - Visually guided finger movements include online feedback of current effector
      position to guide target approach. This visual feedback may be scaled or
      otherwise distorted by unpredictable perturbations. Although adjustments to
      visual feedback scaling have been studied before, the underlying brain activation
      differences between upscaling (visual feedback larger than real movement) and
      downscaling (feedback smaller than real movement) are currently unknown. Brain
      activation differences between upscaling and downscaling might be expected
      because within-trial adjustments during upscaling require corrective backwards
      accelerations, whereas correcting for downscaling requires forward accelerations.
      In this behavioural and fMRI study we investigated adjustments during up- and
      downscaling in a target-directed finger flexion-extension task with real-time
      visual feedback. We found that subjects made longer and more complete within
      trial corrections for downscaling perturbations than for upscaling perturbations.
      The finger task activated primary motor (M1) and somatosensory (S1) areas,
      premotor and parietal regions, basal ganglia, and cerebellum. General scaling
      effects were seen in the right pre-supplementary motor area, dorsal anterior
      cingulate cortex, inferior parietal lobule, and dorsolateral prefrontal cortex.
      Stronger activations for down- than for upscaling were observed in M1,
      supplementary motor area (SMA), S1 and anterior cingulate cortex. We argue that
      these activation differences may reflect differing online correction for
      upscaling vs. downscaling during finger flexion-extension.

PMID- 28503805
TI  - Development of a SiYAlON glaze for improved osteoconductivity of implantable
      medical devices.
AB  - The application of bioactive coatings onto orthopaedic appliances is commonly
      performed to compensate for the otherwise bioinert nature of medical devices and
      to improve their osseointegration. Calcium phosphates, hydroxyapatite (HAp), and
      bioglasses are commercially available for this purpose. Until recently, few other
      inorganic compounds have been identified with similar biofunctionality. However,
      silicon nitride (Si3 N4 ) has emerged as a new orthopaedic material whose unique
      surface chemistry also enhances osteoconductivity. Recent research has confirmed
      that its minority intergranular phase, consisting of silicon yttrium aluminum
      oxynitride (SiYAlON), is principally responsible for this improvement. As a
      result, it was hypothesized that SiYAlON itself might serve as an effective
      osteoconductive coating or glaze for medical devices. To test this hypothesis, a
      process inspired by traditional ceramic whiteware glazing was developed. A slurry
      containing ingredients similar to the intergranular SiYAlON composition was
      applied to a Si3 N4 surface, which was then subjected to a heat treatment to form
      a glaze. Various analytical tools were employed to assess its chemistry and
      morphology. It was found that the glaze was comprised predominately of Y5 Si3 O12
      N, a compound commonly referred to as N-apatite, which is isostructural to native
      HAp. Subsequent exposure of the glazed surface to acellular simulated body fluid
      led to increased deposition of biomimetic HAp-like crystals, while exposure to
      Saos-2 osteosarcoma cells in vitro resulted in greater HAp deposition relative to
      control samples. The observation that SiYAlON exhibits enhanced osteoconductivity
      portends its potential as a therapeutic aid in bone and tissue repair. (c) 2017
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1084
      1096, 2018.

PMID- 28503806
TI  - Distinctiveness Benefits Novelty (and Not Familiarity), but Only Up to a Limit:
      The Prior Knowledge Perspective.
AB  - Novelty is a pivotal player in cognition, and its contribution to superior memory
      performance is a widely accepted convention. On the other hand, mnemonic
      advantages for familiar information are also well documented. Here, we examine
      the role of experimental distinctiveness as a potential explanation for these
      apparently conflicting findings. Across two experiments, we demonstrate that
      conceptual novelty, an unfamiliar combination of familiar constituents, is
      sensitive to its experimental proportions: Improved memory for novelty was
      observed when novel stimuli were relatively rare. Memory levels for familiar
      items, in contrast, were completely unaffected by experimental proportions,
      highlighting their insensitivity to list-based distinctiveness. Finally, no
      mnemonic advantage for conceptual novelty over familiarity was observed even when
      novel stimuli were extremely rare at study. Together, these results imply that
      novel and familiar items are processed via partially distinct mechanisms, with
      (at least some facets of) novelty not providing a mnemonic advantage over
      familiarity.

PMID- 28503807
TI  - Reducing anti-nutritional factor and enhancing yield with advancing time of
      planting and zinc application in grasspea in Ethiopia.
AB  - BACKGROUND: Grasspea (Lathyrus sativus L.) is an important pulse crop for food,
      feed and sustainable crop production systems in Ethiopia. Despite its advantages
      in nutrition and adaptability to harsh climate and low fertile soil, it contains
      a neurotoxin, beta-N-oxalyl-alpha,beta-diamiono propionic acid (beta-ODAP), which
      paralyses the lower limbs and is affected by genotypic and agronomic factors. To
      determine the effect of zinc application and planting date on yield and beta-ODAP
      content of two genotypes, experiments were conducted in two regions of Ethiopia.
      RESULTS: The main effects of variety, sowing date and zinc and their interactions
      were significant (P < 0.001) for beta-ODAP and seed yield, which had a linear
      relationship with zinc. For the improved grasspea variety, an application of 20
      kg ha-1 zinc showed a reduction of beta-ODAP from 0.15% to 0.088% at Debre Zeit
      and 0.14% to 0.08% at Sheno and increased its yield from 841 kg ha-1 to 2260 kg
      ha-1 at Debre Zeit and from 715 to 1835 kg ha-1 at Sheno. Early sowing showed a
      reduction in ODAP content in relation to the late sowing. CONCLUSION: An
      application of Zn beyond even 20 kg ha-1 with an early sowing is recommended for
      the improved variety. (c) 2017 Society of Chemical Industry.

PMID- 28503808
TI  - A pilot randomized study comparing extralevator with conventional
      abdominoperineal excision for low rectal cancer after neoadjuvant chemoradiation.
AB  - AIM: The aims of this study were to assess the feasibility of performing an
      extralevator abdominoperineal excision (ELAPE) after neoadjuvant chemoradiation
      (NCRT), to compare the rates of circumferential resection margin (CRM)
      involvement and intra-operative perforation (IOP) of the specimen, and to assess
      the amount of tissue removed around the muscularis propria (MP)/internal
      sphincter (IS) of the lower rectum in patients with low rectal cancer undergoing
      ELAPE compared with conventional abdominoperineal excision (CAPE) after NCRT.
      METHOD: This was an open-label, parallel-arm pilot randomized trial conducted in
      India. Twenty patients were randomized to one of the study arms. The surgical
      specimens were fixed, serially cross-sectioned and photographed. Using
      specialized morphometry software, the amount of tissue resected with each
      operation was measured. RESULTS: There was a nonsignificant trend towards more
      IOPs (30% vs 0%, P = 0.06) and a higher CRM involvement rate (40% vs 20%, P =
      0.32) in the CAPE arm. ELAPE removed a significantly greater amount of tissue
      around the IS/MP when compared with CAPE (mean +/- SD: 1911.39 +/- 382 mm2 vs
      1132.03 +/- 371 mm2 , P < 0.001). The mean distance from the IS/MP to the CRM was
      significantly greater in the ELAPE arm both in the posterior (mean +/- SD: 28.28
      +/- 3 mm vs 9.63 +/- 3 mm, P < 0.001) and lateral (mean +/- SD: 13.69 +/- 3 mm vs
      9.72 +/- 3 mm, P = 0.009) parts of the rectum but not in the anterior part (mean
      +/- SD: 6.74 +/- 2 mm vs 6.10 +/- 4 mm, P = 0.64). The short-term morbidity was
      not significantly different between the two procedures. CONCLUSION: ELAPE removed
      more tissue in the lower rectum and resulted in a lower rate of IOP and CRM
      involvement when compared with CAPE, even after NCRT.

PMID- 28503809
TI  - Robot-assisted laparoscopic versus open partial nephrectomy in patients with
      chronic kidney disease: A propensity score-matched comparative analysis of
      surgical outcomes.
AB  - OBJECTIVES: To compare surgical outcomes between robot-assisted laparoscopic
      partial nephrectomy and open partial nephrectomy in patients with chronic kidney
      disease. METHODS: Of 550 patients who underwent partial nephrectomy between 2012
      and 2015, 163 patients with T1-2 renal tumors who had an estimated glomerular
      filtration rate between 30 and 60 mL/min/1.73 m2 , and underwent robot-assisted
      laparoscopic partial nephrectomy or open partial nephrectomy were retrospectively
      analyzed. To minimize selection bias between the two surgical methods, patient
      variables were adjusted by 1:1 propensity score matching. RESULTS: The present
      study included 75 patients undergoing robot-assisted laparoscopic partial
      nephrectomy and 88 undergoing open partial nephrectomy. After propensity score
      matching, 40 patients were included in each operative group. The mean
      preoperative estimated glomerular filtration rate was 49 mL/min/1.73 m2 . The
      mean ischemia time was 21 min in robot-assisted laparoscopic partial nephrectomy
      (warm ischemia) and 35 min in open partial nephrectomy (cold ischemia).
      Preservation of the estimated glomerular filtration rate 3-6 months
      postoperatively was not significantly different between robot-assisted
      laparoscopic partial nephrectomy and open partial nephrectomy (92% vs 91%, P =
      0.9348). Estimated blood loss was significantly lower in the robot-assisted
      laparoscopic partial nephrectomy group than in the open partial nephrectomy group
      (104 vs 185 mL, P = 0.0025). The postoperative length of hospital stay was
      shorter in the robot-assisted laparoscopic partial nephrectomy group than in the
      open partial nephrectomy group (P < 0.0001). The prevalence of Clavien-Dindo
      grade 3 complications and a negative surgical margin status were not
      significantly different between the two groups. CONCLUSIONS: In our experience,
      robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy
      provide similar outcomes in terms of functional preservation and perioperative
      complications among patients with chronic kidney disease. However, a lower
      estimated blood loss and shorter postoperative length of hospital stay can be
      obtained with robot-assisted laparoscopic partial nephrectomy.

PMID- 28503811
TI  - The Interactive Origin of Iconicity.
AB  - We investigate the emergence of iconicity, specifically a bouba-kiki effect in
      miniature artificial languages under different functional constraints: when the
      languages are reproduced and when they are used communicatively. We ran
      transmission chains of (a) participant dyads who played an interactive
      communicative game and (b) individual participants who played a matched learning
      game. An analysis of the languages over six generations in an iterated learning
      experiment revealed that in the Communication condition, but not in the
      Reproduction condition, words for spiky shapes tend to be rated by naive judges
      as more spiky than the words for round shapes. This suggests that iconicity may
      not only be the outcome of innovations introduced by individuals, but, crucially,
      the result of interlocutor negotiation of new communicative conventions. We
      interpret our results as an illustration of cultural evolution by random mutation
      and selection (as opposed to by guided variation).

PMID- 28503810
TI  - A minor role of asparaginase in predisposing to cerebral venous thromboses in
      adult acute lymphoblastic leukemia patients.
AB  - Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses
      (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually
      hampers patients' lives and may also endanger efficient leukemia treatment.
      Although many factors have been suggested to account for an elevated risk of VTs
      in patients with ALL, there still is a lack of studies focusing on CVTs and
      especially in the setting of adult ALL patients. We studied in our retrospective
      population-based cohort the occurrence, characteristics, as well as risk factors
      for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a
      national pediatric-inspired treatment protocol ALL2000. In the risk factor
      analyses for VTs we found a distinction of the characteristics of the patients
      acquiring CVT from those with other kinds of VTs or without thrombosis. In
      contrast to previous studies we were also able to compare the effects of
      asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs
      were diagnosed prior the administration of asparaginase which accentuates the
      role of other risk factors on the pathophysiology of CVT compared to truncal or
      central venous line (CVL) VTs in adult ALL patients.

PMID- 28503812
TI  - The difference between cycloplegic and non-cycloplegic autorefraction and its
      association with progression of refractive error in Beijing urban children.
AB  - PURPOSE: To investigate the difference between cycloplegic and non-cycloplegic
      autorefraction and its association with the progression of refractive error in
      Beijing urban children. METHODS: A total of 386 children aged 6-17 years were
      enrolled in the baseline investigation of the Beijing Myopia Progression Study in
      2010. They were invited for follow-up vision examinations in the years 2011,
      2012, and 2013, including cycloplegic (cyclopentolate 1%, three times)
      autorefraction. We investigated the difference between the cycloplegic spherical
      equivalent (SE) and the non-cycloplegic SE (DSE) provided by autorefraction and
      its association with refractive error progression. The progression of refractive
      error was defined as the difference between the cycloplegic SE at follow-up and
      at baseline. RESULTS: Two hundred and nineteen children (57%) with completed
      refractive data (mean +/- standard deviation: -1.36 +/- 2.44 D at baseline) were
      ultimately enrolled. The DSE reduced from 0.51 +/- 0.72 D at baseline to 0.19 +/-
      0.43 D in the third year of follow-up (p = 0.01). The baseline DSE was positively
      associated with the children's baseline cycloplegic refraction (beta = 0.193
      dioptre dioptre-1 , p < 0.001). After further divided by refractive status, the
      DSE was consistently higher in the hyperopic group than in either the emmetropic
      or myopic groups at each follow-up (all p < 0.001). In the multivariate
      regression analysis, the myopic children with larger baseline DSE (beta = -0.404
      dioptre dioptre-1 , p = 0.01) exhibited more myopic refractive change. However,
      baseline DSE was not found to be a significant risk factor (relative risk, 95%
      confidence interval: 1.06, 0.79-1.41) for those with newly developed myopia.
      CONCLUSION: In this sample, the children's DSE was found to be increased as the
      hyperopic refraction increased. Furthermore, greater the DSE was associated with
      the progression of refractive error among the myopic children, but not with the
      onset of myopia.

PMID- 28503813
TI  - Molecular characterization of equine infectious anaemia virus from a major
      outbreak in southeastern France.
AB  - In 2009, a major outbreak of equine infectious anaemia (EIA) was reported in the
      south-east of France. This outbreak affected three premises located in the Var
      region where the index case, a 10-year-old mare that exhibited clinical signs
      consistent with EIA, occurred at a riding school. Overall, more than 250 horses
      were tested for EIAV (equine infectious anaemia virus) antibodies, using agar gel
      immunodiffusion test, and 16 horses were positive in three different holdings.
      Epidemiological survey confirmed that the three premises were related through the
      purchase/sale of horses and the use of shared or nearby pastures. Molecular
      characterization of viruses was performed by sequencing the full gag gene
      sequence (1,400 bp) of the proviral DNAs retrieved from the spleen of infected
      animals collected post-mortem. Phylogenetic analysis confirmed epidemiological
      data from the field, as viruses isolated from the three premises were clustering
      together suggesting a common origin whereas some premises were 50 km apart.
      Moreover, viruses characterized during this outbreak are different from European
      strains described so far, underlying the high genetic diversity of EIAV in
      Europe.

PMID- 28503814
TI  - Diabetes mellitus and risk of early-onset Alzheimer's disease: a population-based
      case-control study.
AB  - BACKGROUND AND PURPOSE: Previous studies have reported that diabetes is a risk
      factor for both all-cause and vascular dementia; however, diabetes as a risk
      factor for Alzheimer's disease (AD) remains controversial. Therefore, the aim was
      to elucidate the association between diabetes and early-onset AD. METHODS: A case
      control study was conducted using a population-based database that included
      medical and pharmacy claims and insurance eligibility data, from beneficiaries of
      corporate employees and their dependent family members. Cases were aged 40-64
      years and were first prescribed medications for AD between 2005 and 2016. Up to
      four controls matched for age, sex and hospital type were included for each case.
      Data were analyzed using conditional logistic regression and compared between the
      sexes. RESULTS: Data from 371 patients with AD (mean age 56.3 +/- 5.3 years; 48%
      female) and 1484 controls were analyzed. Use of antidepressants, antipsychotics
      and antithrombotics during the index month was higher amongst patients with AD
      (19.4%, 34.5% and 11.3%, respectively) than amongst controls (2.9%, 10.3% and
      7.3%, respectively). Our findings suggest no evidence for an association between
      diabetes and risk of early-onset AD (adjusted odds ratio 1.31; 95% confidence
      interval 0.90-1.92). In the subgroup analyses, adjusted odds ratios in patients
      with diabetes were 0.73 (95% confidence interval 0.38-1.39) and 1.68 (95%
      confidence interval 1.06-2.67) for female and male patients, respectively.
      CONCLUSIONS: There is no apparent association between diabetes and risk of early
      onset AD in the total study population, although a weak association was observed
      amongst male patients.

PMID- 28503815
TI  - Body Mass Normalization for Lateral Abdominal Muscle Thickness Measurements in
      Adolescent Athletes.
AB  - OBJECTIVES: To determine the value of allometric parameters for ultrasound
      measurements of the oblique external (OE), oblique internal (OI), and transversus
      abdominis (TrA) muscles in adolescent athletes. The allometric parameter is the
      slope of the linear regression line between the log-transformed body mass and log
      transformed muscle size measurement. METHODS: The study included 114 male
      adolescent football players between the ages of 10 and 19 years. All individuals
      with no surgical procedures performed on the trunk area and who had played a
      sport for at least 2 years were included. A real-time B-mode ultrasound scanner
      with a linear array transducer was used to obtain images of the lateral abdominal
      muscles from both sides of the body. A stabilometric platform was used to assess
      the body mass value. RESULTS: The correlations between body mass and the OE, OI,
      and TrA muscle thicknesses were r = 0.73, r = 0.79, and r = 0.64, respectively
      (in all cases, P < .0001). The allometric parameters were 0.77 for the OE, 0.67
      for the OI, and 0.61 for the TrA. Using these parameters, no significant
      correlations were found between body mass and the allometric-scaled thickness of
      the lateral abdominal muscles. CONCLUSIONS: Significant positive correlations
      exist between body mass and lateral abdominal muscle thickness in adolescent
      athletes. Therefore, it is reasonable to advise that the values of the allometric
      parameters for the OE, OI, and TrA muscles obtained in this study should be used,
      and the allometric-scaled thicknesses of those muscles should be analyzed in
      future research on adolescent athletes.

PMID- 28503817
TI  - Influence of feeding a fish oil-containing diet to mature, overweight dogs:
      Effects on lipid metabolites, postprandial glycaemia and body weight.
AB  - The objective of this study was to determine the effect of feeding a fish oil
      (FO)-containing diet on lipid and protein metabolism, postprandial glycaemia and
      body weight (BW) of mature, overweight dogs. Seven female dogs were randomly
      assigned to one of two isonitrogenous and isocaloric diets, control (CO) or FO
      (FO), in a crossover design. Experimental periods were 69 day, separated by a
      washout period of 30 day. At the beginning of the experiment, and at 30 and 60
      day of feeding the experimental diets, the dogs were infused with D-glucose (2
      g/kg BW) through an intravenous catheter. Blood samples were collected for 3 hr
      to perform a glucose tolerance test. Nitrogen balance measurements began at 06:30
      on d 63 of each experimental period and ended at 06:30 on d 69. On d 66 of each
      period, a single dose (7.5 mg/kg) of 15 N-glycine was administered orally for
      determination of protein turnover. Incremental area under the curve and glucose
      concentration at peak did not differ between treatments or among sampling days
      within treatment. Glucose half-life tended to decrease (p < .10) in the FO
      treatment on day 30 when compared to baseline (day 0). beta-hydroxybutyrate, non
      esterified fatty acid (NEFA) and triglycerides did not differ within or between
      treatments. Cholesterol decreased (p < .05) on the FO treatment on day 30, 60 and
      69 when compared to day 0. High-density lipoprotein (HDL) decreased (p < .05) in
      the FO treatment on day 69 when compared to day 0. Body weight, food intake,
      faecal excretion, DM and N digestibilities, N balance and protein turnover were
      not different between diets. Overall, FO-containing diet decreases cholesterol in
      mature overweight dogs; however, further research is warranted to verify the
      effects of FO on glucose metabolism.

PMID- 28503816
TI  - Xanthophylls increased HDLC level and nuclear factor PPARgamma, RXRgamma and
      RARalpha expression in hens and chicks.
AB  - This study was designed to investigate effects of xanthophylls on serum lipid
      profile (triglyceride, TG; cholesterol, CHO; high-density lipoprotein
      cholesterol, HDLC; and low-density lipoprotein cholesterol, LDLC) and nuclear
      factor (peroxisome proliferator-activated receptor gamma, PPARgamma; PPAR gamma
      coactivator 1 alpha, PGC1alpha; retinoid X receptor gamma, RXRgamma; and retinoic
      acid receptor alpha, RARalpha) gene expression of breeding hens and chicks. In
      experiment 1, 432 hens were divided into three groups and fed diets supplemented
      with 0 (as control group), 20 or 40 mg/kg xanthophylls. Blood was sampled at 7,
      14, 21, 28 and 35 days of trial. Liver, duodenum, jejunum and ileum were sampled
      at 35 days of trial. Results showed that serum HDLC level of hens was increased
      after dietary 40 mg/kg xanthophyll addition for 21, 28 and 35 days, while serum
      TG, CHO and LDLC were not affected. Xanthophyll addition also increased PPARgamma
      expression in jejunum, RXRgamma expression in duodenum and jejunum, and RARalpha
      expression in liver and duodenum. Experiment 2 was a 2 * 2 factorial design. Male
      chicks hatched from 0 or 40 mg/kg xanthophyll diet of hens were fed diet
      containing either 0 or 40 mg/kg xanthophylls. Liver, duodenum, jejunum and ileum
      were sampled at 0, 7, 14 and 21 days after hatching. Blood samples were also
      collected at 21 days. Results showed that in ovo xanthophylls elevated PPARgamma
      in duodenum and jejunum, and RXRgamma and RARalpha in liver of chicks mainly
      within 1 week after hatching, while dietary xanthophylls increased serum HDLC
      level and PPARgamma and RXRgamma in liver from 2 weeks onwards. In conclusion,
      our research suggested xanthophylls can regulate serum lipid profile and nuclear
      factor expression in hens and chicks.

PMID- 28503818
TI  - Lidocaine for pain control during intrauterine device insertion.
AB  - AIM: The aim of this study was to compare the effects of topical lidocaine spray,
      cream and injection on pain perception during intrauterine device (IUD)
      insertion. METHODS: Multiparous women of reproductive age were randomized into
      control, lidocaine cream, spray and injection groups. A 10 cm visual analog scale
      was used for all patients to evaluate pain during the three steps of the IUD
      insertion procedure. Baseline pain assessment was made immediately after the
      administration of analgesics, the second pain assessment was performed
      immediately after use of the tenaculum, and the third pain assessment was
      performed after IUD insertion. RESULTS: Two hundred patients were enrolled in the
      study. The groups were similar in terms of demographic characteristics. The
      lidocaine injection group exhibited higher baseline pain scores (P < 0.001). Pain
      associated with tenaculum use was lower in the lidocaine spray group. Pain
      related to IUD insertion was lower in the lidocaine spray and injection groups (P
      < 0.001); however, lidocaine spray was superior to injection for the reduction of
      IUD insertion related pain (P = 0.001). CONCLUSION: Lidocaine spray is a good
      option for reducing the pain experienced during insertion of an IUD. It reduces
      pain related to both tenaculum use and IUD insertion. Spray application is both
      easy and rapid. Paracervical lidocaine injection also reduces pain during IUD
      insertion, but has no effect on tenaculum-related pain; moreover, the injection
      itself is painful. Therefore, this option is not a plausible method for reducing
      pain during IUD insertion.

PMID- 28503819
TI  - Nomenclature for factors of the HLA system, update March 2017.

PMID- 28503820
TI  - The P2X7 receptor-NLRP3 inflammasome complex predicts the development of non
      Hodgkin's lymphoma in Sjogren's syndrome: a prospective, observational, single
      centre study.
AB  - BACKGROUND: P2X7 receptor (P2X7R), trigger of acute inflammatory responses via
      the NLRP3 inflammasome, is hyperfunctioning in patients with Sjogren's syndrome
      (SS), where it stimulates IL-18 production. Some patients with SS develop a
      mucosa-associated lymphoid tissue non-Hodgkin's lymphoma (MALT-NHL). OBJECTIVES:
      To prospectively evaluate the involvement and the putative prognostic role of
      this inflammatory pathway in the development of MALT-NHL. METHODS: A total of 147
      women with SS have been prospectively followed for a mean of 52 months, relating
      the expression and function of the P2X7R-inflammasome axis in salivary glands and
      circulating lymphomonocytes to the prognosis and the degree of the disease.
      RESULTS: At baseline, gene expression of P2X7R and of the inflammasome components
      NLRP3, caspase-1 and IL-18 increased according to the presence of germinative
      centres and was higher in autoantibody-positive individuals and strongly higher
      in those developing a MALT-NHL over the follow-up. Glandular expression of IL-18
      was threefold higher in MALT-NHL than in controls or in the other patients with
      SS. P2X7R did not colocalize with generic markers of inflammatory infiltrate,
      like CD20, being selectively expressed by epithelial cells. P2X4R, sharing
      functional characteristics with P2X7R, did not differ in SS and controls. The
      increased P2X7R gene and protein expression was tissue specific, no difference
      being observed in peripheral lymphomonocytes between SS with MALT-NHL and SS not
      developing MALT-NHL. CONCLUSION: We propose the P2X7R-inflammasome axis as a
      novel potential pathway involved in both SS exocrinopathy and lymphomagenesis,
      reinforcing the hypothesis of a key role of IL-18, via its increased P2X7R
      mediated production, in the pathogenesis of lymphoproliferative malignancies, and
      opening novel opportunities for the early diagnosis of lymphoproliferative
      complications and the development of potential targeted therapies.

PMID- 28503822
TI  - Constitutional mismatch repair deficiency in a healthy child: On the spot
      diagnosis?
AB  - Constitutional mismatch repair deficiency (CMMRD) is a rare, recessively
      inherited childhood cancer predisposition syndrome caused by biallelic germline
      mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with
      that of neurofibromatosis type 1 (NF1), since many patients have multiple cafe-au
      lait macules (CALM) and other NF1 signs, but no germline NF1 mutations. We report
      of a case of a healthy 6-year-old girl who fulfilled the diagnostic criteria of
      NF1 with >6 CALM and freckling. Since molecular genetic testing was unable to
      confirm the diagnosis of NF1 or Legius syndrome and the patient was a child of
      consanguineous parents, we suspected CMMRD and found a homozygous PMS2 mutation
      that impairs MMR function. Current guidelines advise testing for CMMRD only in
      cancer patients. However, this case illustrates that including CMMRD in the
      differential diagnosis in suspected sporadic NF1 without causative NF1 or SPRED1
      mutations may facilitate identification of CMMRD prior to cancer development. We
      discuss the advantages and potential risks of this CMMRD testing scenario.

PMID- 28503821
TI  - Effects of continuous low dose infusion of lipopolysaccharide on inflammatory
      responses, milk production and milk quality in dairy cows.
AB  - The objective of this study was to evaluate the effects of continuous low dose
      infusion of lipopolysaccharide (LPS) on inflammatory responses and milk
      production and quality in lactating dairy cows. Eight Holstein cows were assigned
      to two treatments in a cross-over experimental design. Cows were infused
      intravenously either with saline solution or with saline solution containing LPS
      from Escherichia coli O111:B4 at a dose of 0.01 MUg LPS/kg body weight for
      approximately 6 hr each day during a seven-day trial. The clinical symptoms and
      milk production performance were observed. Milk samples were analysed for
      conventional components, fatty acids and amino acids. And jugular vein and
      mammary vein plasma samples were analysed for concentrations of cytokines and
      acute phase proteins. LPS infusion decreased feed intake and milk yield. An
      increase in body temperature was observed after LPS infusion. LPS infusion also
      increased plasma concentrations of interleukin-1beta, serum amyloid A, LPS
      binding protein, C-reactive protein and haptoglobin. LPS infusion decreased the
      contents of some fatty acids, such as C17:1, C18:0, C18:1n9 (trans) and C18:2n6
      (trans), and most amino acids except for methionine, threonine, histidine,
      cysteine, tyrosine and proline in the milk. The results indicated that a
      continued low dose infusion of LPS can induce an inflammatory response, decrease
      milk production and reduce milk quality.

PMID- 28503824
TI  - An index to predict asthma in wheezing young children produced promising initial
      results.

PMID- 28503823
TI  - Impact of surgery on survival in stage IV breast cancer.

PMID- 28503825
TI  - New insights into Ca2+ channel function in health and disease.

PMID- 28503826
TI  - Prospective randomized trial of neoadjuvant chemotherapy during the 'wait period'
      following preoperative chemoradiotherapy for rectal cancer: results of the WAIT
      trial.
AB  - AIM: The aim was to determine whether the addition of additional cycles of
      chemotherapy during the 'wait period' following neoadjuvant chemoradiotherapy for
      rectal cancer improves the pathological complete response (pCR) rate. METHOD:
      Rectal cancer patients were randomly allocated either to a standard 10 week wait
      period before surgery (standard chemoradiotherapy, SCRT) or to receive three
      cycles of fluorouracil based chemotherapy following chemoradiotherapy during a
      similar 10 week wait (extended chemoradiotherapy, XCRT). The primary end-point
      was pCR as determined by blinded pathological assessment. RESULTS: Forty-nine
      patients were randomized (SCRTn = 24, XCRTn = 25). pCR occurred in 10 patients
      overall but there was no significant difference in pCR between the groups (SCRTn
      = 6, XCRTn = 4, P = 0.49). CONCLUSION: The addition of three cycles of 5
      fluorouracil/leucovorin in a 10 week wait period after conventional
      chemoradiotherapy seems to result in similar pCR rates in patients with locally
      advanced rectal cancer based on this small randomized trial.

PMID- 28503827
TI  - Comparison of non-invasive tear film stability measurement techniques.
AB  - BACKGROUND: Measurement of tear film stability is commonly used to give an
      indication of tear film quality but a number of non-invasive techniques exists
      within the clinical setting. This study sought to compare three non-invasive tear
      film stability measurement techniques: instrument-mounted wide-field white light
      clinical interferometry, instrument-mounted keratoscopy and hand-held
      keratoscopy. METHODS: Twenty-two subjects were recruited in a prospective,
      randomised, masked, cross-over study. Tear film break-up or thinning time was
      measured non-invasively by independent experienced examiners, with each of the
      three devices, in a randomised order, within an hour. RESULTS: Significant
      correlation was observed between instrument-mounted interferometric and
      keratoscopic measurements (p < 0.001) but not between the hand-held device and
      the instrument-mounted techniques (all p > 0.05). Tear film stability values
      obtained from the hand-held device were significantly shorter and demonstrated
      narrower spread than the other two instruments (all p < 0.05), while no
      significant differences were observed between the two instrument-mounted devices
      (all p > 0.05). CONCLUSION: Good clinical agreement exists between the instrument
      mounted interferometric and keratoscopic measurements but not between the hand
      held device and either of the instrument-mounted techniques. The results
      highlight the importance of specifying the instrument employed to record non
      invasive tear film stability.

PMID- 28503828
TI  - Birthweight and cardiovascular risk factors in a Japanese general population.
AB  - AIM: This study was conducted to examine whether babies born small develop
      cardiovascular problems in later life. METHODS: Data were examined
      retrospectively for 1241 city dwellers (men 521, women 720) aged 40-69 years who
      received a medical examination at a single institution. Blood tests, physical
      measurements, and a questionnaire survey regarding birth weight (small, medium,
      large), medication history and lifestyle (alcohol consumption, smoking, exercise)
      was administered. We selected 28 persons (12 men and 16 women) from and studied
      the rate of conformity between the participants' memory (small, medium, large)
      and the actual birth weight recorded in their maternal and child health handbook
      (< 2500, 2500-3500, > 3500 g). RESULTS: Participants' recall of their birth
      weight correlated well with the weight recorded in the maternal notebook (r =
      0.73; P < 0.025). Low-density lipoprotein (P < 0.05), and total cholesterol (P <
      0.01) levels in men, and systolic (P < 0.05) and diastolic (P < 0.05) blood
      pressure in women were significantly inversely related to birth weight when
      controlling for age, body mass index, medication, and lifestyle. The percentage
      of women born small, medium, and large taking antidiabetic agents was 17.8%, 2.9%
      and 0% (P < 0.05), respectively. CONCLUSION: A low birth weight was associated
      with high low-density lipoprotein and total cholesterol levels in men, and
      hypertension and diabetes mellitus in women aged 40-69.

PMID- 28503829
TI  - Unravelling seed dispersal through fragmented landscapes: Frugivore species
      operate unevenly as mobile links.
AB  - Seed dispersal constitutes a pivotal process in an increasingly fragmented world,
      promoting population connectivity, colonization and range shifts in plants.
      Unveiling how multiple frugivore species disperse seeds through fragmented
      landscapes, operating as mobile links, has remained elusive owing to
      methodological constraints for monitoring seed dispersal events. We combine for
      the first time DNA barcoding and DNA microsatellites to identify, respectively,
      the frugivore species and the source trees of animal-dispersed seeds in forest
      and matrix of a fragmented landscape. We found a high functional complementarity
      among frugivores in terms of seed deposition at different habitats (forest vs.
      matrix), perches (isolated trees vs. electricity pylons) and matrix sectors
      (close vs. far from the forest edge), cross-habitat seed fluxes, dispersal
      distances and canopy-cover dependency. Seed rain at the landscape-scale, from
      forest to distant matrix sectors, was characterized by turnovers in the
      contribution of frugivores and source-tree habitats: open-habitat frugivores
      replaced forest-dependent frugivores, whereas matrix trees replaced forest trees.
      As a result of such turnovers, the magnitude of seed rain was evenly distributed
      between habitats and landscape sectors. We thus uncover key mechanisms behind
      "biodiversity-ecosystem function" relationships, in this case, the relationship
      between frugivore diversity and landscape-scale seed dispersal. Our results
      reveal the importance of open-habitat frugivores, isolated fruiting trees and
      anthropogenic perching sites (infrastructures) in generating seed dispersal
      events far from the remnant forest, highlighting their potential to drive
      regeneration dynamics through the matrix. This study helps to broaden the "mobile
      link" concept in seed dispersal studies by providing a comprehensive and
      integrative view of the way in which multiple frugivore species disseminate seeds
      through real-world landscapes.

PMID- 28503830
TI  - Synthetic OCP heterodimers are photoactive and recapitulate the fusion of two
      primitive carotenoproteins in the evolution of cyanobacterial photoprotection.
AB  - The orange carotenoid protein (OCP) governs photoprotection in the majority of
      cyanobacteria. It is structurally and functionally modular, comprised of a C
      terminal regulatory domain (CTD), an N-terminal effector domain (NTD) and a
      ketocarotenoid; the chromophore spans the two domains in the ground state and
      translocates fully into the NTD upon illumination. Using both the canonical OCP1
      from Fremyella diplosiphon and the presumably more primitive OCP2 paralog from
      the same organism, we show that an NTD-CTD heterodimer forms when the domains are
      expressed as separate polypeptides. The carotenoid is required for the
      heterodimeric association, assembling an orange complex which is stable in the
      dark. Both OCP1 and OCP2 heterodimers are photoactive, undergoing light-driven
      heterodimer dissociation, but differ in their ability to reassociate in darkness,
      setting the stage for bioengineering photoprotection in cyanobacteria as well as
      for developing new photoswitches for biotechnology. Additionally, we reveal that
      homodimeric CTD can bind carotenoid in the absence of NTD, and name this
      truncated variant the C-terminal domain-like carotenoid protein (CCP). This
      finding supports the hypothesis that the OCP evolved from an ancient fusion event
      between genes for two different carotenoid-binding proteins ancestral to the NTD
      and CTD. We suggest that the CCP and its homologs constitute a new family of
      carotenoproteins within the NTF2-like superfamily found across all kingdoms of
      life.

PMID- 28503831
TI  - Can Neuroscience Contribute to Practical Ethics? A Critical Review and Discussion
      of the Methodological and Translational Challenges of the Neuroscience of Ethics.
AB  - Neuroethics is an interdisciplinary field that arose in response to novel ethical
      challenges posed by advances in neuroscience. Historically, neuroethics has
      provided an opportunity to synergize different disciplines, notably proposing a
      two-way dialogue between an 'ethics of neuroscience' and a 'neuroscience of
      ethics'. However, questions surface as to whether a 'neuroscience of ethics' is a
      useful and unified branch of research and whether it can actually inform or lead
      to theoretical insights and transferable practical knowledge to help resolve
      ethical questions. In this article, we examine why the neuroscience of ethics is
      a promising area of research and summarize what we have learned so far regarding
      its most promising goals and contributions. We then review some of the key
      methodological challenges which may have hindered the use of results generated
      thus far by the neuroscience of ethics. Strategies are suggested to address these
      challenges and improve the quality of research and increase neuroscience's
      usefulness for applied ethics and society at large. Finally, we reflect on
      potential outcomes of a neuroscience of ethics and discuss the different
      strategies that could be used to support knowledge transfer to help different
      stakeholders integrate knowledge from the neuroscience of ethics.

PMID- 28503832
TI  - The Voluntary Nature of Decision-Making in Addiction: Static Metaphysical Views
      Versus Epistemologically Dynamic Views.
AB  - The degree of autonomy present in the choices made by individuals with an
      addiction, notably in the context of research, is unclear and debated. Some have
      argued that addiction, as it is commonly understood, prevents people from having
      sufficient decision-making capacity or self-control to engage in choices
      involving substances to which they have an addiction. Others have criticized this
      position for being too radical and have counter-argued in favour of the full
      autonomy of people with an addiction. Aligning ourselves with middle-ground
      positions between these two extremes, we flesh out an account of voluntary action
      that makes room for finer-grained analyses than the proposed all-or-nothing
      stances, which rely on a rather static metaphysical understanding of the nature
      of the voluntariness of action. In contrast, a dynamic concept of voluntary
      action better accounts for varying levels of voluntariness of the person with an
      addiction which takes into consideration internal (e.g. cravings) and external
      (e.g. perceptions of degrees of freedom related to different options)
      determinants of choice. Accordingly, like other components of autonomous choices
      such as level of information, voluntariness can fluctuate. Therefore, there are
      important implications for research and clinical ethics in matters of consent,
      recruitment, and therapeutic approaches. Overall, our proposal is inspired by a
      pragmatist understanding of voluntary action, notably with respect to how
      voluntariness is both informed by actions and experiences that shape one's view
      of the world.

PMID- 28503833
TI  - Moral Enhancement Meets Normative and Empirical Reality: Assessing the Practical
      Feasibility of Moral Enhancement Neurotechnologies.
AB  - Moral enhancement refers to the possibility of making individuals and societies
      better from a moral standpoint. A fierce debate has emerged about the ethical
      aspects of moral enhancement, notably because steering moral enhancement in a
      particular direction involves choosing amongst a wide array of competing options,
      and these options entail deciding which moral theory or attributes of the moral
      agent would benefit from enhancement. Furthermore, the ability and effectiveness
      of different neurotechnologies to enhance morality have not been carefully
      examined. In this paper, we assess the practical feasibility of moral enhancement
      neurotechnologies. We reviewed the literature on neuroscience and cognitive
      science models of moral judgment and analyzed their implications for the specific
      target of intervention (cognition, volition or affect) in moral enhancement. We
      also reviewed and compared evidence on available neurotechnologies that could
      serve as tools of moral enhancement. We conclude that the predictions of
      rationalist, emotivist, and dual process models are at odds with evidence, while
      different intuitionist models of moral judgment are more likely to be aligned
      with it. Furthermore, the project of moral enhancement is not feasible in the
      near future as it rests on the use of neurointerventions, which have no moral
      enhancement effects or, worse, negative effects.

PMID- 28503834
TI  - Respect for Autonomy in Light of Neuropsychiatry.
AB  - Bioethics needs an elaborated concept of autonomy based on empirical knowledge
      about the prerequisites of the capacity of autonomy. Whereas Beauchamp and
      Childress, and many other bioethicists have discussed social influences on the
      capacity of autonomy in depth, neurobiological influences have received less
      attention. A comprehensive concept of autonomy should consider both social and
      biological factors that can diminish the capacity of autonomy. This article
      focuses on neurobiological influences that can reduce the capacity of autonomy.
      The thesis of this article is that the integration of neuropsychiatric knowledge
      into the concept of autonomy is essential for (1) evaluating demands for harmful
      medical treatments which might be caused by a brain disease, and (2) deciding on
      involuntary treatments of patients who suffer from substantial lack of autonomy
      due to neuropsychiatric disorders. Diametrically opposed to such a comprehensive
      concept of the capacity of autonomy is the concept of 'liberty of illness'. In
      Germany, this concept is supported not only by anti-psychiatric groups but also
      by the Federal Constitutional Court. Several real cases demonstrate how the brain
      can be 'hijacked' by parasites, antibodies or technical devices. Applying the
      concept of 'liberty of illness' to persons whose decision-making capacity is
      severely affected by neuropsychiatric disorders is cynical. These patients
      neither chose their disease nor would refuse effective treatment if their will
      was not disturbed by the disease. Respect for autonomy should be understood as
      the positive obligation to save, support or restore the biological prerequisites
      of the capacity for autonomous decision-making.

PMID- 28503835
TI  - Neuroethics: Neuroscience's Contributions to Bioethics.

PMID- 28503836
TI  - Role of anticholinergic burden in primary care patients with first cognitive
      complaints.
AB  - BACKGROUND AND PURPOSE: Drugs with anticholinergic properties might have a
      negative impact on cognition, but findings are still conflicting. The association
      was evaluated between anticholinergic drugs and cognitive performance in primary
      care patients with first cognitive complaints. METHODS: From April 2013 to March
      2014, 353 general practitioners administered the Mini-Mental State Examination
      (MMSE) to patients presenting with first cognitive complaints. Drug history was
      collected and the anticholinergic cognitive burden (ACB) was scored and
      categorized as ACB 0, ACB 1 and ACB 2+. A mixed effect linear regression model
      was used to assess the association between ACB and MMSE score. RESULTS: Of 4249
      subjects entering the study (mean age 77 +/- 8.2 years, 66.4% women and mean
      years of schooling 8.9 +/- 4.5), 25.8% received at least one drug with
      anticholinergic action. According to multivariate analysis, and after adjustment
      for several confounders, subjects with ACB 2+ had a statistically significant
      lower MMSE score compared with those with ACB 0 (beta -0.63; 95% confidence
      interval -1.19; -0.07). Subjects with ACB 1 had a non-statistically significant
      lower MMSE score than those with ACB 0 (beta -0.11; 95% confidence interval 
      0.37; 0.15). CONCLUSIONS: Anticholinergic medication might affect cognitive
      function in people with first cognitive complaints. Alternatives should be taken
      into account when possible, balancing the benefits and harms of these
      medications.

PMID- 28503839
TI  - Introduction to the Special Issue on Proteases and Proteolysis in Health and
      Disease.
AB  - This Special Issue on Proteases and Proteolysis in Health and Disease comprises
      11 reviews that cover a broad range of topics in this diverse field. We hope you
      find these pieces as engaging and informative as we have and we are grateful to
      their authors for taking the time to write for The FEBS Journal.

PMID- 28503837
TI  - Efficacy of protocol-based pharmacotherapy management on anticoagulation with
      warfarin for patients with cardiovascular surgery.
AB  - WHAT IS KNOWN AND OBJECTIVE: Anticoagulation therapy with warfarin requires
      periodic monitoring of prothrombin time-international normalized ratio (PT-INR)
      and adequate dose adjustments based on the data to minimize the risk of bleeding
      and thromboembolic events. In our hospital, we have developed protocol-based
      pharmaceutical care, which we called protocol-based pharmacotherapy management
      (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing
      of blood sampling for measuring PT-INR and warfarin dosage determination based on
      an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by
      comparing to conventional pharmaceutical care. METHODS: From October 2013 to June
      2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries
      received post-operative warfarin therapy. The early series of patients received
      warfarin therapy as the conventional care (control group, n=77), whereas the
      latter received warfarin therapy based on the PBPM (PBPM group, n=68). These
      patients formed the cohort of the present study and were retrospectively
      analysed. RESULTS: The indications for warfarin included aortic valve replacement
      (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial
      fibrillation (n=29). There were no differences in patients' characteristics
      between both groups. The percentage time in therapeutic range in the first 10
      days was significantly higher in the PBPM group (47.1%) than that in the control
      group (34.4%, P<.005). The average time to reach the steady state was
      significantly (P<.005) shorter in the PBPM group compared to the control group
      (7.3 vs 8.6 days). WHAT IS NEW AND CONCLUSION: Warfarin therapy based on our
      novel PBPM was clinically safe and resulted in significantly better
      anticoagulation control compared to conventional care.

PMID- 28503840
TI  - A Critical Note on Treatment of a Severe Diltiazem Intoxication: High-Dose
      Calcium and Glucagon Infusions.
AB  - The morbidity and mortality of a severe calcium channel blocker intoxication is
      high due to serious toxic cardiac effects. Its treatment is supported by low
      quality evidence from the heterogeneous literature. We describe a case of a
      severe diltiazem intoxication and critically appraise the efficacy and role of
      high-dose calcium and glucagon infusions. A 53-year-old woman was admitted to the
      emergency department with a cardiogenic shock with complete AV block, not
      responding to atropine, isoprenaline and an external pacemaker. Later on, it
      became clear that she had a severe diltiazem intoxication which was successfully
      treated with isotone fluids, inotropes, vasopressors and continuous infusion of
      high-dose calcium and glucagon. The patient developed, however, an acute,
      necrotizing pancreatitis, probably related to iatrogenic high calcium levels.
      This case demonstrates lack of consensus regarding target levels of serum calcium
      for treatment of a severe diltiazem intoxication. Goal-directed tapering of
      calcium should prevent side effects of iatrogenic hypercalcaemia. The
      contribution of glucagon infusions is doubtful due to the instability of
      solubilized glucagon. This might explain why the effect of glucagon is variable
      in the literature.

PMID- 28503841
TI  - Social networks of adults with an intellectual disability from South Asian and
      White communities in the United Kingdom: A comparison.
AB  - BACKGROUND: Little research exists comparing the social networks of people with
      intellectual disability (ID) from South Asian and White backgrounds. This UK
      study reports on the barriers that South Asian people with intellectual
      disability face in relation to social inclusion compared to their White
      counterparts. MATERIALS AND METHODS: A mixed-methods research design was adopted
      to explore the social lives of 27 men (15 White; 12 South Asian) and 20 women (10
      White; 10 South Asian with intellectual disability). Descriptive and parametric
      tests were used to analyse the quantitative data. RESULTS: The average network
      size of the whole group was 32 members. South Asian participants had more family
      members whilst White participants had more service users and staff in their
      networks; 96% network members from White intellectual disability group were also
      of White background, whilst the South Asian group had mixed ethnic network
      members. CONCLUSIONS: Social networks of individuals with intellectual disability
      in this study were found to be larger overall in comparison with previous
      studies, whilst network structure differed between the White and South Asian
      population. These differences have implications relating to future service
      planning and appropriateness of available facilities.

PMID- 28503842
TI  - Demographic histories of three predatory lady beetles reveal complex patterns of
      diversity and population size change in the United States.
AB  - Predatory lady beetles (Coccinellidae) contribute to biological control of
      agricultural pests, however, multiple species frequently compete for similar
      resources in the same environment. Numerous studies have examined ecological
      interactions among the native North American convergent lady beetle (Hippodamia
      convergens) and two introduced species, the seven-spotted lady beetle (Coccinella
      septempunctata) and the Asian lady beetle (Harmonia axyridis), in agricultural
      fields and described multiyear population dynamics. However, the evolutionary
      dynamics of these interacting species of predatory beetles are uncharacterized.
      We utilize publicly available multilocus genotype data from geographically
      disjunct populations of these three species to estimate demography across North
      American populations. Coalescent analyses reveal (1) a recent (~4-5 years)
      decline (>12 fold) in microsatellite effective population size of H. convergens,
      while expanding (mutation scaled growth rate in 1/u generations = 2910, SD = 362)
      over evolutionary time scales, (2) a massive (>150 fold), and very recent,
      effective population size decline in Ha. axyridis, and (3) population size growth
      (mutation scaled growth rate = 997, SD = 60) over recent and evolutionary time
      scales in C. septempunctata. Although these estimates are based on genetic data
      with different mutation rates and patterns of inheritance (mitochondrial versus
      nuclear), these dynamic and differing population size histories are striking.
      Further studies of the interactions of these predatory lady beetles in the field
      are thus warranted to explore the consequences of population size change and
      biological control activities for evolutionary trajectories in North America.

PMID- 28503843
TI  - The volume, cost and outcomes of pancreatic resection in a regional centre in New
      Zealand.
AB  - BACKGROUND: The frequency, costs and outcome of pancreatic resection (both
      pancreaticoduodenectomy and distal pancreatectomy) were reviewed in our own
      institution and correlated with regional population growth as well as national
      resection rates and locations. METHODS: Demographic, pathological and outcome
      data on pancreaticoduodenectomy and distal pancreatectomy were obtained from a
      prospectively maintained database for the years 2005-2009 and 2010-2014. During
      this period, the catchment population grew from 460 000 to 567 000. Costing
      information was obtained from the hospital-independent costing and coding
      committee, and the locations and rates of pancreatic resection were obtained by
      interrogating the national minimum dataset. RESULTS: A total of 41
      pancreatectomies (29 pancreaticoduodenectomy, 12 distal pancreatectomy) were
      performed between 2005 and 2009, increasing to 84 pancreatectomies (55
      pancreaticoduodenectomies, 27 distal pancreatectomies and two total
      pancreatectomies) between 2010 and 2014. This constituted one sixth of the
      national volume of pancreatic resections. There was no difference in patient
      demographics or indications for resection between the two time periods; however,
      portal vein resection was used more frequently in the second period. Margin
      positivity rate decreased (7 of 41 versus 8 of 84) and lymph node harvest
      increased (median 8 nodes versus median 15 nodes) between the two time periods.
      Overall 30-day mortality was 1.6%. CONCLUSION: In New Zealand, regional rates of
      pancreatic resection reflect regional population demands, and institutional
      growth is driven by local population requirements. Institutional growth can be
      achieved with the maintenance of internationally accepted outcomes and quality
      indicators.

PMID- 28503845
TI  - The specificity of the neural response to speech at birth.
AB  - In this work we ask whether at birth, the human brain responds uniquely to
      speech, or if similar activation also occurs to a non-speech surrogate
      'language'. We compare neural activation in newborn infants to the language heard
      in utero (English), to an unfamiliar language (Spanish), and to a whistled
      surrogate language (Silbo Gomero) that, while used by humans to communicate, is
      not speech. Anterior temporal areas of the neonate cortex are activated in
      response to both familiar and unfamiliar spoken language, but these classic
      language areas are not activated to the whistled surrogate form. These results
      suggest that at the time human infants emerge from the womb, the neural
      preparation for language is specialized to speech.

PMID- 28503844
TI  - TypeLoader: A fast and efficient automated workflow for the annotation and
      submission of novel full-length HLA alleles.
AB  - Recent years have seen a rapid increase in the discovery of novel allelic
      variants of the human leukocyte antigen (HLA) genes. Commonly, only the exons
      encoding the peptide binding domains of novel HLA alleles are submitted. As a
      result, the IPD-IMGT/HLA Database lacks sequence information outside those
      regions for the majority of known alleles. This has implications for the
      application of the new sequencing technologies, which deliver sequence data often
      covering the complete gene. As these technologies simplify the characterization
      of the complete gene regions, it is desirable for novel alleles to be submitted
      as full-length sequences to the database. However, the manual annotation of full
      length alleles and the generation of specific formats required by the sequence
      repositories is prone to error and time consuming. We have developed TypeLoader
      to address both these facets. With only the full-length sequence as a starting
      point, Typeloader performs automatic sequence annotation and subsequently handles
      all steps involved in preparing the specific formats for submission with very
      little manual intervention. TypeLoader is routinely used at the DKMS Life Science
      Lab and has aided in the successful submission of more than 900 novel HLA alleles
      as full-length sequences to the European Nucleotide Archive repository and the
      IPD-IMGT/HLA Database with a 95% reduction in the time spent on annotation and
      submission when compared with handling these processes manually. TypeLoader is
      implemented as a web application and can be easily installed and used on a
      standalone Linux desktop system or within a Linux client/server architecture.
      TypeLoader is downloadable from http://www.github.com/DKMS-LSL/typeloader.

PMID- 28503846
TI  - Tailored-made robotic abdominoperineal resection, using the da Vinci Xi, for a
      regrowth of rectal tumour after complete clinical response - a video vignette.

PMID- 28503847
TI  - Addition of Color Doppler Sonography for Detection of Amniotic Fluid Disturbances
      and Its Implications on Perinatal Outcomes.
AB  - OBJECTIVES: To determine whether color Doppler sonography increases the detection
      of pregnancies at risk for adverse outcomes. METHODS: Participants admitted to
      labor and delivery with the anticipation of a vaginal delivery underwent
      measurements of amniotic fluid volume (AFV) using amniotic fluid index (AFI) and
      single deepest pocket (SDP) techniques by grayscale followed by color Doppler
      sonography. Oligohydramnios was defined as an AFI of less than 5 cm or an SDP of
      less than 2 cm. Intrapartum and perinatal outcomes were compared between
      participants with a diagnosis of a low AFV by grayscale and color Doppler
      sonography. RESULTS: Over 42 months, 428 women were enrolled in the study. Color
      Doppler sonography resulted in lower AFV estimates (mean +/- SD by the AFI, 10.7
      +/- 3.7 cm by grayscale sonography and 8.6 +/- 3.6cm by color Doppler sonography;
      P < .0001). For the SDP, the mean AFVs were 4.6 +/- 2.0 cm by grayscale
      sonography and 3.4 +/- 1.4 cm by color Doppler sonography (P < .0001). The level
      of agreement between grayscale and color Doppler sonography in estimating the AFV
      was fair, with kappa = 0.32 for the AFI and 0.28 for the SDP. Outcome measures of
      AFVs classified as low based on color Doppler sonography (normal by grayscale
      sonography) and those classified as low by grayscale sonography (low by color
      Doppler sonography) were compared. There was no difference in composite perinatal
      complications, mode of delivery, or composite neonatal complications.
      CONCLUSIONS: The use of color Doppler sonography leads to the overdiagnosis of
      low AFVs and does not appear to increase the detection of pregnancies destined
      for adverse intrapartum or perinatal outcomes.

PMID- 28503848
TI  - In Response: Ultrasound-assisted Lumbar Puncture on Infants in the Pediatric
      Emergency Department.

PMID- 28503849
TI  - Meaning and object in Freud's theory of language.
AB  - This article sets out to challenge the interpretation of Freud's views on the
      origins of the meaning of language according to which meaning always originates
      from an act of naming. In Freud's terms, word-presentations would originally
      denote object- or thing-presentations and gain meaning through this reference.
      This interpretation claims that this view was already expressed in Freud's On
      Aphasia (1891) and influenced all his later theory of language. To oppose this
      claim, three conceptions proposed by Freud are discussed that strongly suggest
      the participation of language in the construction of the field of objects: a
      metapsychological hypothesis (the concepts of word-, thing-, and object
      presentation), the explanation of a psychopathological phenomenon (the genesis of
      a fetishistic object-choice), and a concept concerning the foundations of the
      psychoanalytic method of dream interpretation (secondary elaboration). As a
      conclusion, it is argued that Freud's early views in On Aphasia (1891) can be
      alternatively understood such as to allow for a different view of language and
      its relationship with objects.

PMID- 28503850
TI  - Roles of spermine in modulating the antioxidant status and Nrf2 signalling
      molecules expression in the thymus and spleen of suckling piglets-new insight.
AB  - This study aimed to investigate the effects of spermine and extended spermine
      administration on the antioxidant status and expression of NF-E2-related factor 2
      (Nrf2) signalling molecules in the thymus and spleen in suckling piglets. One
      half of eighty 12-day-old suckling piglets obtained sufficient nutrient intake
      supplemented with spermine (0.4 mmol/kg body weight), and another half received
      restricted nutrient intake supplemented with physiological saline in equal doses
      once a day for 7 hr or 3, 6 or 9 days in pairs. Spermine supplementation and its
      extended duration significantly decreased malondialdehyde (MDA) and protein
      carbonyl (PC) contents (p < .05), but markedly improved antisuperoxide anion
      (ASA), antihydroxyl radical (AHR), catalase (CAT), total superoxide dismutase (T
      SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) and
      glutathione-S-transferase (GST) activities (p < .05) and glutathione (GSH)
      content (p < .05) in the thymus and spleen. Additionally, real-time PCR analysis
      showed that spermine administration and extended spermine intake reduced Kelch
      like ECH-associated protein 1 (Keap1) gene transcription and enhanced SOD1, GPx1,
      CAT, glutathione reductase (GR) and Nrf2 mRNA levels of the thymus and spleen (p
      < .05), and also improved GST gene expression in the thymus (p < .05). Notably,
      the spermine-supplemented time for the optimal effects of suckling piglet was
      determined to be 6 days. Collectively, the current study suggested that spermine
      supplementation and extended spermine administration could protect the health of
      the thymus and spleen from early weaning by enhancing the antioxidant status and
      regulating the expression of antioxidant-related signalling molecules.

PMID- 28503851
TI  - Characterizing bacterial communities in paper production-troublemakers revealed.
AB  - Biofilm formation is a major cause of reduced paper quality and increased down
      time during paper manufacturing. This study uses Illumina next-generation
      sequencing to identify the microbial populations causing quality issues due to
      their presence in biofilms and slimes. The paper defects investigated contained
      traces of the films and/or slime of mainly two genera, Tepidimonas and
      Chryseobacterium. The Tepidimonas spp. found contributed on average 68% to the
      total bacterial population. Both genera have been described previously to be
      associated with biofilms in paper mills. There was indication that Tepidimonas
      spp. were present as compact biofilm in the head box of one paper machine and was
      filtered out by the paper web during production. On the other hand Tepidimonas
      spp. were also present to a large extent in the press and white waters of two
      nonproblematic paper machines. Therefore, the mere presence of a known biofilm
      producer alone is not sufficient to cause slimes and therefore paper defects and
      other critical factors are additionally at play. For instance, we identified
      Acidovorax sp., which is an early colonizer of paper machines, exhibiting the
      ability to form extracellular DNA matrices for attachment and biofilm formation.

PMID- 28503853
TI  - Glucuronidation and its impact on the bioactivity of [6]-shogaol.
AB  - SCOPE: -shogaol (6S) from ginger has been reported to have diverse bioactivities
      and can be widely metabolized in animals and humans; however, the impact of
      glucuronidation on its bioactivity is still largely unknown. This study
      investigates the glucuronidation of 6S and its effect on cell cytotoxicity and
      Nrf2-inducing activities of 6S. METHODS AND RESULTS: The glucuronidated
      metabolite of 6S, 4-O-monoglucuronide 6S (6S-G), was synthesized and
      characterized for the first time. Glucuronidation of 6S in humans was studied
      using microsomes of the liver and intestine and recombinant UDP
      glucuronosyltransferase (UGTs). The kinetics of 6S glucuronidation by human liver
      and intestinal microsomes followed the substrate inhibition kinetics model. The
      intrinsic glucuronidation clearance (CLint ) of 6S in human liver microsomes was
      higher than that in human intestine microsomes. Among the recombinant UGTs
      examined, UGT1A1, 1A3, 1A6, 1A8, 1A10, 2B7, 2B15, and 2B17 exhibited
      glucuronidation activity toward 6S, with UGT2B7 being the most potent one.
      Compared with 6S, the glucuronidation of 6S largely eliminated its cell
      cytotoxicity against human colon cancer cell lines HT-116 and HT-29, and its Nrf2
      inducing activity. CONCLUSION: The findings from current study provide
      foundations for understanding the role of glucuronidation in biotransformation
      and biological activities of 6S.

PMID- 28503855
TI  - Mechanical optic neuropathy in high myopia.

PMID- 28503854
TI  - Nomenclature for factors of the HLA system, updated on January 2017.

PMID- 28503852
TI  - Smoking-associated morbidities on computed tomography lung cancer screens in HIV
      infected smokers.

PMID- 28503856
TI  - Pyrazolo[4,3-h]quinoline Ligand-Based Iridium(III) Complexes for
      Electrochemiluminescence.
AB  - Electrochemiluminescence (ECL) based on [Ru(bpy)3 ]2+ systems is widely utilized
      for immunoassays. In order to extend the promising potential of ECL-based
      applications, IrIII complexes have recently attracted attention as probes because
      of their excellent luminescent properties and tunable emission wavelength. Here
      we describe a series of Ir complexes using a large pi-conjugated ligand and
      different ancillary chelates. The complexes synthesized have been chemically and
      spectroscopically characterized and used for ECL measurements with annihilation
      and co-reactant methods. One of the IrIII complexes investigated exhibits the
      brightest, ever reported, ECL efficiency in acetonitrile employing the benzoyl
      peroxide (BPO) co-reactant method.

PMID- 28503857
TI  - Recent developments in structural studies on acetylcholinesterase.
AB  - This review focuses on several recent developments concerning structure-function
      relationships in vertebrate acetylcholinesterase. These include studies on high
      resolution structures of human acetylcholinesterase and its complexes; the first
      crystal structure of a snake venom acetylcholinesterase, in which open and closed
      states of the 'back door' are visualized; a powerful algorithm for redesigning
      proteins for enhanced expression in prokaryotic systems, as applied to human
      acetylcholinesterase, which has hitherto been an intractable target; in situ
      implementation of 'click chemistry' in crystalline acetylcholinesterase, which
      yields novel insights into the steric and dynamic changes involved in the
      reaction within the active-site gorge; and a study that demonstrates the effect
      of crystallization conditions on ligand alignment within a protein complex, in
      this case the methylene blue-Torpedo californica acetylcholinesterase complex,
      which highlights the relevance of the precipitant employed to structure-based
      drug design. This is an article for the special issue XVth International
      Symposium on Cholinergic Mechanisms.

PMID- 28503859
TI  - Principles for being theoretical-Increasing the impact of research conducted in
      primary care.
AB  - Primary care is a unique research environment and is difficult to study well
      without disrupting the delivery of care. Recent developments in implementation
      and care delivery sciences have facilitated real world tests of interventions.
      However primary care research often misses a foundational component of quality -
      "being theoretical." Using cancer prevention and control as an example, this
      commentary advocates for the imperative of using theory to guide research and
      describes three principles for being theoretical. These principles, readily
      amenable to clinical settings, will produce studies that do more than answer "did
      it work?" and therefore increase the impact of primary care-based research across
      the cancer continuum.

PMID- 28503858
TI  - LdtR is a master regulator of gene expression in Liberibacter asiaticus.
AB  - Huanglongbing or citrus greening disease is causing devastation to the citrus
      industry. Liberibacter asiaticus, an obligate intracellular pathogen of citrus,
      is one the causative agents of the disease. Most of the knowledge about this
      bacterium has been deduced from the in silico exploration of its genomic
      sequence. L. asiaticus differentially expresses genes during its transmission
      from the psyllid vector, Diaphorina citri, to the plant. However, the regulatory
      mechanisms for the adaptation of the bacterium into either hosts remain unknown.
      Here we show that LdtR, a MarR family transcriptional regulator, activates or
      represses transcription genome-wide. We performed a double approach to identify
      the components of the LdtR regulon: a transcriptome analysis in both the related
      bacterium Liberibacter crescens and citrus-infected leaves, strengthened with an
      in silico prediction of LdtR regulatory sites. Our results demonstrated that LdtR
      controls the expression of nearly 180 genes in L. asiaticus, distributed in
      processes such as cell motility, cell wall biogenesis, energy production, and
      transcription. These results provide new evidence about the regulatory network of
      L. asiaticus, where the differential expression of genes from these functional
      categories could be of great importance during the adaptation of the bacterium to
      either hosts.

PMID- 28503861
TI  - Estimates of subgroup treatment effects in overall nonsignificant trials: To what
      extent should we believe in them?
AB  - In drug development, it sometimes occurs that a new drug does not demonstrate
      effectiveness for the full study population but appears to be beneficial in a
      relevant subgroup. In case the subgroup of interest was not part of a
      confirmatory testing strategy, the inflation of the overall type I error is
      substantial and therefore such a subgroup analysis finding can only be seen as
      exploratory at best. To support such exploratory findings, an appropriate
      replication of the subgroup finding should be undertaken in a new trial. We
      should, however, be reasonably confident in the observed treatment effect size to
      be able to use this estimate in a replication trial in the subpopulation of
      interest. We were therefore interested in evaluating the bias of the estimate of
      the subgroup treatment effect, after selection based on significance for the
      subgroup in an overall "failed" trial. Different scenarios, involving continuous
      as well as dichotomous outcomes, were investigated via simulation studies. It is
      shown that the bias associated with subgroup findings in overall nonsignificant
      clinical trials is on average large and varies substantially across plausible
      scenarios. This renders the subgroup treatment estimate from the original trial
      of limited value to design the replication trial. An empirical Bayesian shrinkage
      method is suggested to minimize this overestimation. The proposed estimator
      appears to offer either a good or a conservative correction to the observed
      subgroup treatment effect hence provides a more reliable subgroup treatment
      effect estimate for adequate planning of future studies.

PMID- 28503860
TI  - Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast
      cancer through AKT and NF-kappaB signaling.
AB  - ADAMTS18 dysregulation plays an important role in many disease processes
      including cancer. We previously found ADAMTS18 as frequently methylated tumor
      suppressor gene (TSG) for multiple carcinomas, however, its biological functions
      and underlying molecular mechanisms in breast carcinogenesis remain unknown.
      Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell
      lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with
      their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in
      70.8% of tumor tissues by methylation-specific PCR, but none of the normal
      tissues. Demethylation treatment restored ADAMTS18 expression in silenced breast
      cell lines. Ectopic expression of ADAMTS18 in breast tumor cells resulted in
      inhibition of cell migration and invasion. Nude mouse model further confirmed
      that ADAMTS18 suppressed breast cancer metastasis in vivo. Further mechanistic
      studies showed that ADAMTS18 suppressed epithelial-mesenchymal transition (EMT),
      further inhibited migration and invasion of breast cancer cells. ADAMT18
      deregulated AKT and NF-kappaB signaling, through inhibiting phosphorylation
      levels of AKT and p65. Thus, ADAMTS18 as an antimetastatic tumor suppressor
      antagonizes AKT and NF-kappaB signaling in breast tumorigenesis. Its methylation
      could be a potential tumor biomarker for breast cancer.

PMID- 28503862
TI  - Letter: hepatitis B virus reactivation in patients with chronic hepatitis C
      during direct-acting anti-viral therapy.

PMID- 28503863
TI  - Editorial: is it time for therapeutic drug monitoring of anti-TNF agents during
      pregnancy? Maybe, maybe not.

PMID- 28503864
TI  - Editorial: evidence is growing for protective effects of 5-aminosalicylates
      against colitis-associated cancer-authors' reply.

PMID- 28503865
TI  - Editorial: visceral fat as a predictor of post-operative recurrence of Crohn's
      disease-Authors' reply.

PMID- 28503866
TI  - Editorial: evidence is growing for protective effects of 5-aminosalicylates
      against colitis-associated cancer.

PMID- 28503867
TI  - Editorial: visceral fat as a predictor of post-operative recurrence of Crohn's
      disease.

PMID- 28503868
TI  - Editorial: is it time for therapeutic drug monitoring of anti-TNF agents during
      pregnancy? Maybe, maybe not. Author's reply.

PMID- 28503869
TI  - Letter: hepatitis B reactivation in patients with chronic hepatitis C during
      direct-acting antiviral therapy-authors' reply.

PMID- 28503870
TI  - Correcting hazard ratio estimates for outcome misclassification using multiple
      imputation with internal validation data.
AB  - OBJECTIVE: Outcome misclassification may occur in observational studies using
      administrative databases. We evaluated a two-step multiple imputation approach
      based on complementary internal validation data obtained from two subsamples of
      study participants to reduce bias in hazard ratio (HR) estimates in Cox
      regressions. METHODS: We illustrated this approach using data from a surveyed
      sample of 6247 individuals in a study of statin-diabetes association in Quebec.
      We corrected diabetes status and onset assessed from health administrative data
      against self-reported diabetes and/or elevated fasting blood glucose (FBG)
      assessed in subsamples. The association between statin use and new onset diabetes
      was evaluated using administrative data and the corrected data. By simulation, we
      assessed the performance of this method varying the true HR, sensitivity,
      specificity, and the size of validation subsamples. RESULTS: The adjusted HR of
      new onset diabetes among statin users versus non-users was 1.61 (95% confidence
      interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when
      diabetes status and onset were corrected based on self-report and undiagnosed
      diabetes (FBG >= 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report
      and undiagnosed diabetes/impaired FBG (>= 6 mmol/L). In simulations, the multiple
      imputation approach yielded less biased HR estimates and appropriate coverage for
      both non-differential and differential misclassification. Large variations in the
      corrected HR estimates were observed using validation subsamples with low
      participation proportion. The bias correction was sometimes outweighed by the
      uncertainty introduced by the unknown time of event occurrence. CONCLUSION:
      Multiple imputation is useful to correct for outcome misclassification in time-to
      event analyses if complementary validation data are available from subsamples.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28503871
TI  - Subcellular distribution of calcium during spermatogenesis of zebrafish, Danio
      rerio.
AB  - Calcium plays a variety of vital regulatory functions in many physiological and
      biochemical events in the cell. The aim of this study was to describe the
      ultrastructural distribution of calcium during different developmental stages of
      spermatogenesis in a model organism, the zebrafish (Danio rerio), using a
      combined oxalate-pyroantimonate technique. Samples were treated by potassium
      oxalate and potassium pyroantimonate during two fixation stages and examined
      using transmission electron microscopy to detect electron dense intracellular
      calcium. The subcellular distribution of intracellular calcium was characterized
      in spermatogonium, spermatocyte, spermatid, and spermatozoon stages. The area
      which is covered by intracellular calcium in different stages was quantified and
      compared using software. Isolated calcium deposits were mainly detectable in the
      cytoplasm and the nucleus of the spermatogonium and spermatocyte. In the
      spermatid, calcium was partially localized in the cytoplasm as isolated deposits.
      However, most calcium was transformed from isolated deposits into an unbound pool
      (free calcium) within the nucleus of the spermatid and the spermatozoon.
      Interestingly, in the spermatozoon, calcium was mainly localized in a form of an
      unbound pool which was detectable as an electron-dense mass within the nucleus.
      Also, sporadic calcium deposits were scattered in the midpiece and flagellum. The
      proportional area which was covered by intracellular calcium increased
      significantly from early to late stages of spermatogenesis. The extent of the
      area which was covered by intracellular calcium in the spermatozoon was the
      highest compared to earlier stages. Calcium deposits were also observed in the
      somatic cells (Sertoli, myoid, Leydig) of zebrafish testis. The notable changes
      in the distribution of intracellular calcium of germ cells during different
      developmental stages of zebrafish spermatogenesis suggest its different
      homeostasis and physiological functions during the process of male gamete
      development.

PMID- 28503872
TI  - The effect of brief digital interventions on attitudes to intellectual
      disability: Results from a pilot study.
AB  - BACKGROUND: Evidence on the effects of contact and education based interventions
      on attitudes is limited in the intellectual disability field. This study compared
      the effects of brief interventions with different education, indirect and
      imagined contact components on lay people's attitudes. MATERIALS AND METHODS: 401
      adult participants were randomised to six digital brief interventions consisting
      of different combinations of education, indirect and imagined contact. Their
      attitudes, intergroup anxiety and social distance were assessed post-intervention
      and at four to six-week follow-up. RESULTS: An intervention combining film-based
      education about intellectual disability and indirect contact had small positive
      effects on all three outcomes. Social distance was further reduced with the
      addition of a positively toned imagined contact task. These effects were
      maintained at follow-up. CONCLUSIONS: A brief film-based digital intervention can
      have small positive effects on attitudes to people with intellectual
      disabilities. These may be enhanced by adding positive imagined contact.

PMID- 28503873
TI  - Successful large volume 'lymphocentesis' for refractory lymphoedema in lower and
      upper limbs.

PMID- 28503874
TI  - Disturbances in blood flow and 'medicine's greatest imitator'.
AB  - First described in 1959, intravascular lymphoma (IVL) remains one of the most
      clinically challenging diagnoses due to its diverse and non-specific clinical
      manifestations and evasiveness in detection by standard investigations. Indeed,
      IVL deserves the title of 'medicine's greatest imitator'. We highlight a case of
      IVL where the diagnosis came too late in the clinical course, detected by random
      skin biopsy. Clinicians should strongly consider this diagnosis in presentations
      with persistent symptomatology despite appropriate interventions.

PMID- 28503875
TI  - A rare vascular complication in a patient with essential thrombocythaemia:
      spontaneous abdominal aortic dissection.
AB  - A 27-year-old woman complained of waist and back pain. Abdominal computed
      tomography angiography showed abdominal aortic dissection, the blood count
      revealed a high platelet count of 1655 * 109 /L. Negative for JAK2V617F, CALR and
      MPL mutations (i.e. triple-negative), the patient was diagnosed as essential
      thrombocythaemia (ET) with abdominal aortic dissection and was treated with
      cytoreduction and antiplatelet drugs. Cases of abdominal aortic dissection in ET
      have not been previously reported. As such, we proposed a mechanism of abdominal
      aortic dissection caused by endothelial dysfunction and further emphasised
      appropriate management in ET with abdominal aortic dissection.

PMID- 28503876
TI  - The Melbourne thunderstorm asthma event: can we avert another strike?

PMID- 28503877
TI  - Follicular lymphoma in pregnancy presenting as multiple aneuploidy on non
      invasive prenatal testing.

PMID- 28503878
TI  - Complementary and alternative medicine: conventional solution to an
      unconventional problem.

PMID- 28503879
TI  - Impact of an antimicrobial stewardship intervention on appropriateness of
      prescribing for community-acquired pneumonia in an Australian regional hospital.
AB  - Community-acquired pneumonia (CAP) is the second commonest indication for
      antibiotic use in Australian hospitals and is therefore a frequent target for
      antimicrobial stewardship. A single-centre prospective study was conducted in a
      regional referral hospital comparing management of adult patients with CAP before
      and after an educational intervention. We demonstrated a reduction in duration of
      therapy and reduced inappropriate use of ceftriaxone-based regimens for non
      severe CAP.

PMID- 28503880
TI  - Individualised medicine: why we need Bayesian dosing.
AB  - Individualised drug dosing has been shown to improve patient outcomes and reduce
      adverse drug events. One method of individualised medicine is the Bayesian
      approach, which uses prior information about how the population responds to
      therapy, to inform clinicians about how a specific individual is responding to
      their current therapy. This information is then used to make changes to the dose.
      Studies using a Bayesian approach to adjust drug dosing have shown that
      clinicians are able to achieve a therapeutic range quicker than standard
      practice. If concentration is related to a pharmacodynamic end-point, this means
      that the drug will be more effective, and the side-effects will be minimised.
      Unfortunately, the software options to assist with Bayesian dosing in Australia
      are limited. The aims of this article are to demystify the concepts of Bayesian
      dosing, set the context of the Bayesian approach using reference to other dosing
      strategies and discuss its benefits over current dosing methods for a number of
      drugs. The article is targeted to medical and pharmacy clinicians, and there is a
      practical clinical case to demonstrate how this method could be used in everyday
      clinical practice.

PMID- 28503881
TI  - A case of de novo diagnosis anti-neutrophil cytoplasmic antibody-negative pauci
      immune necrotising glomerulonephritis in pregnancy.

PMID- 28503882
TI  - Editor's Note.

PMID- 28503883
TI  - Deaths from liver cancer continue to rise in Australia: is elimination by 2030
      possible?

PMID- 28503884
TI  - Do professional medical colleges serve a function in the 21st century?

PMID- 28503885
TI  - Thunderstorm asthma.

PMID- 28503886
TI  - Life-threatening drug interactions: what the physician needs to know.
AB  - Adverse drug-drug interactions are a significant cause of adverse events and
      outcomes. Their incidence is rising, with more patients taking more drugs, and
      newer, more precise but often more hazardous drugs becoming available. Despite
      considerable information, including computerised alerts about potential adverse
      drug-drug interactions, prescribers increasingly override alerts, possibly
      symptomatic of the immense problem of evaluating the risk of an interaction in a
      particular patient. Many reports emanate from small studies often of normal and
      young volunteers, entirely different from the real world where, more often, older
      patients with multiple health conditions are receiving many more than the two
      drugs identified in the drug interaction report. Focusing on those drug-drug
      interactions that are clinically relevant is necessary, and increasingly, tools
      and reliable sources of this information are easily accessible.

PMID- 28503887
TI  - Editor's Note.

PMID- 28503888
TI  - Cryoglobulinaemic glomerulonephritis: artefacts associated with laboratory
      diagnosis and need for renal biopsy.
AB  - Cryoglobulinemia as a cause of renal impairment is uncommon but needs to be
      considered in viral hepatitis and haematological malignancies. Often detection
      and estimation of cryoglobulins are confounded by collection and processing
      errors. This report highlights the need for stringent processing measures if the
      clinical suspicion is high.

PMID- 28503889
TI  - Lanthanide Metal-Organic Framework Microrods: Colored Optical Waveguides and
      Chiral Polarized Emission.
AB  - Lanthanide metal-organic frameworks (Ln-MOFs) have received much attention owing
      to their structural tunability and widely photofunctional applications. However,
      successful examples of Ln-MOFs with well-defined photonic performances at micro
      /nanometer size are still quite limited. Herein, self-assemblies of 1,3,5
      benzenetricarboxylic acid (BTC) and lanthanide ions afford isostructural
      crystalline Ln-MOFs. Tb-BTC, Eu@Tb-BTC, and Eu-BTC have 1D microrod morphologies,
      high photoluminescence (PL) quantum yields, and different emission colors (green,
      orange, and red). Spatially PL resolved spectra confirm that Ln-MOF microrods
      exhibit an optical waveguide effect with low waveguide loss coefficient
      (0.012~0.033 dB MUm-1 ) during propagation. Furthermore, these microrods feature
      both linear and chiral polarized photoemission with high anisotropy.

PMID- 28503890
TI  - Comorbidity and quality of life in childhood cancer survivors treated with proton
      beam therapy.
AB  - BACKGROUND: The rate of childhood cancer survival has recently reached >80%.
      Various adverse events among childhood cancer survivors (CCS) have been reported.
      Proton beams are able to avoid unnecessary irradiation to normal/vital organs. We
      conducted a quality of life (QOL) study for CCS who were treated with proton beam
      therapy (PBT). METHODS: We included those patients treated with PBT to the brain,
      head, or neck and who were <=15 years old at the University of Tsukuba Hospital
      between 1983 and 2011. Clinical information was collected from medical records.
      Questionnaires including the Pediatric Quality of Life Inventory (PedsQL) 4.0
      Generic Core Scales (which assess health-related quality of life) were sent to
      the families/patients. RESULTS: Sixty patients were included. Median age at
      treatment was 6.2 years. The number of patients with status alive/dead/unknown
      was 32/24/4. Median follow-up period was 63.0 months (range, 48-340 months) for
      survivors. Questionnaires were sent to 25 families/patients and 19 were returned.
      PedsQL was assessed for 17 patients. Eleven of 32 living patients had at least
      one comorbidity grade 3/4. Average QOL score was above that for Japanese
      schoolchildren and adolescents. There was no correlation with comorbidity, and
      only longer time from treatment was correlated with a higher PedsQL score (P =
      0.006). CONCLUSION: CCS who were treated with multimodal treatment using PBT had
      a higher QOL score. Higher score was related to longer time since treatment,
      regardless of comorbidity.

PMID- 28503891
TI  - The use of intravesical gentamicin to treat recurrent urinary tract infections in
      lower urinary tract dysfunction.
AB  - AIMS: To assess the use of intravesical gentamicin to treat intractable recurrent
      urinary tract infections in lower urinary tract dysfunction. METHODS: A two
      center retrospective cohort study of 27 patients treated with intravesical
      gentamicin was performed over a 2-year period. A treatment protocol was
      developed, reviewed, and accepted by the clinical effectiveness committee of both
      hospitals. Patients were taught to instill the gentamicin into the bladder on a
      nightly basis. Inclusion criteria included failure to respond to standard
      therapy, having six or more cultured confirmed UTIs over a 12-month period, or at
      least one hospital admission with sepsis. Serum gentamicin levels were taken
      after 7 days and the treatment was discontinued if the level was >1 mg/L.
      Patients were counseled about the limited evidence base for this treatment.
      RESULTS: Twenty-seven patients have been treated with intravesical gentamicin for
      an average of 26 months. Seventeen were performing ISC, five had suprapubic
      catheters, three were voiding, and two had ileal conduits at the time of
      instituting treatment. All patients started on daily 80 mg gentamicin. Twenty two
      patients had less frequently occurring infections after starting intravesical
      gentamicin treatment. Six stopped the treatment and none had side effects as a
      result of the instillations. CONCLUSIONS: This study has shown that in a small
      group of adult patients who have multiple symptomatic UTIs refractory to
      conventional treatment, intravesical gentamicin is effective in reducing the
      frequency of infections. The treatment is well tolerated with no evidence of
      systemic absorption.

PMID- 28503892
TI  - The Ethics of Clinical Trials Research in Severe Mood Disorders.
AB  - Mood disorders, including major depressive disorder (MDD) and bipolar disorder
      (BD), are highly prevalent, frequently disabling, and sometimes deadly.
      Additional research and more effective medications are desperately needed, but
      clinical trials research in mood disorders is fraught with ethical issues.
      Although many authors have discussed these issues, most do so from a theoretical
      viewpoint. This manuscript uses available empirical data to inform a discussion
      of the primary ethical issues raised in mood disorders research. These include
      issues of consent and decision-making capacity, including patients' motivations
      for participating in research. We also address drug withdrawals, placebo
      controls, and the overall safety of research. Finally, we examine the extant
      literature for studies discussing potential indirect benefits of clinical trials
      research to participants. Taken together, the evidence suggests that clinical
      trials research incorporating drug withdrawals and placebo controls can be
      conducted safely and ethically, even in patients with severe or treatment
      resistant mood disorders. In fact, given the dearth of effective treatment
      options for this population, it is our opinion that a moral imperative exists to
      extend the offer of research participation to severely ill or treatment-resistant
      groups.

PMID- 28503894
TI  - Direct Mechanism of the First Carbon-Carbon Bond Formation in the Methanol-to
      Hydrocarbons Process.
AB  - In the past two decades, the reaction mechanism of C-C bond formation from either
      methanol or dimethyl ether (DME) in the methanol-to-hydrocarbons (MTH) process
      has been a highly controversial issue. Described here is the first observation of
      a surface methyleneoxy analogue, originating from the surface-activated DME, by
      in situ solid-state NMR spectroscopy, a species crucial to the first C-C bond
      formation in the MTH process. New insights into the first C-C bond formation were
      provided, thus suggesting DME/methanol activation and direct C-C bond formation
      by an interesting synergetic mechanism, involving C-H bond breakage and C-C bond
      coupling during the initial methanol reaction within the chemical environment of
      the zeolite catalyst.

PMID- 28503895
TI  - Quantitative comparative analysis of the nasal chemosensory organs of anurans
      during larval development and metamorphosis highlights the relative importance of
      chemosensory subsystems in the group.
AB  - The anuran peripheral olfactory system is composed of a number of subsystems,
      represented by distinct neuroepithelia. These include the main olfactory
      epithelium and vomeronasal organ (found in most tetrapods) and three specialized
      epithelia of anurans: the buccal-exposed olfactory epithelium of larvae, and the
      olfactory recess and middle chamber epithelium of postmetamorphic animals. To
      better characterize the developmental changes in these subsystems across the life
      cycle, morphometric changes of the nasal chemosensory organs during larval
      development and metamorphosis were analyzed in three different anuran species
      (Rhinella arenarum, Hypsiboas pulchellus, and Xenopus laevis). We calculated the
      volume of the nasal chemosensory organs by measuring the neuroepithelial area
      from serial histological sections at four different stages. In larvae, the
      vomeronasal organ was relatively reduced in R. arenarum compared with the other
      two species; the buccal-exposed olfactory epithelium was absent in X. laevis, and
      best developed in H. pulchellus. In postmetamorphic animals, the olfactory
      epithelium (air-sensitive organ) was relatively bigger in terrestrial species (R.
      arenarum and H. pulchellus), whereas the vomeronasal and the middle chamber
      epithelia (water-sensitive organs) was best developed in X. laevis. A small
      olfactory recess (likely homologous with the middle chamber epithelium) was found
      in R. arenarum juveniles, but not in H. pulchellus. These results support the
      association of the vomeronasal and middle chamber epithelia with aquatic
      olfaction, as seen by their enhanced development in the secondarily aquatic
      juveniles of X. laevis. They also support a role for the larval buccal-exposed
      olfactory epithelium in assessment of oral contents: it was absent in X. laevis,
      an obligate suspension feeder, while present in the two grazing species. These
      initial quantitative results give, for the first time, insight into the
      functional importance of the peripheral olfactory subsystems across the anuran
      life cycle.

PMID- 28503893
TI  - A comparison of two sources of methionine supplemented at different levels on
      heat shock protein 70 expression and oxidative stress product of Peking ducks
      subjected to heat stress.
AB  - The aim of this study was to examine the effects of different sources and levels
      of methionine (Met) on Heat shock proteins HSP70 expression and protein
      carbonylation in liver, HSP70 expression and malondialdehyde (MDA) concentration
      in intestine under heat stress conditions during summer. A total of 720 (4 days
      old) Peking ducks were placed 20 per pen into six replicates for each of the six
      treatments with a 2 * 3 factorial arrangement, such that two sources of Met (DL
      methionine [DLM] and DL-2-hydroxy-4-methylthiobutyrate [HMTBA] were supplemented
      at three different levels (0.05%, 0.20%, or 0.35% on as-fed basis respectively).
      The experiment was divided into a starter (day 4-16) and a grower (day 17-35)
      period. Diet supplemented with 0.35% Met significantly up-regulated the HSP70
      mRNA expression in duodenum, jejunum and ileum on day 16 and 35 as well as in
      liver on day 35 (p < .05) of ducks. HMTBA-supplemented diets increased the HSP70
      mRNA expression in duodenum, jejunum, ileum and liver on day 35 (p < .01). An
      increased MDA concentration was detected in jejunum of birds in 0.35% DLM
      supplemented treatment on day 16 (p < .05). And decreased protein carbonylation
      concentration was found in DLM-supplemented treatment on day 16 (p < .01). The
      birds fed with 0.35% Met supplemental diet displayed lower hepatic protein
      carbonylation on day 16 (p < .05). In conclusion, supplementation of 0.35% Met in
      the duck diet showed up-regulated HSP70 expression in small intestine and liver,
      which may provide new perspective to the mechanism of Met function. At the same
      time, DLM supplemented in diet may ameliorate oxidative status of liver, while
      HMTBA supplementation may partially improve the intestinal oxidative status of
      Peking ducks.

PMID- 28503896
TI  - Antibacterial efficacy of poly(vinyl alcohol) composite nanofibers embedded with
      silver-anchored silica nanoparticles.
AB  - Silver has been widely used as an effective antibacterial agent especially for
      treating burns and wounds. However, release of silver from materials often arouse
      side effects due to toxicity of silver towards mammalian cells. Argyria and
      argyrosis are well known problems of acute toxicity of silver towards human body.
      Immobilization of silver is an effective approach to reduce silver release.
      Herein, we present poly(vinyl alcohol) (PVA) composite nanofibers embedded with
      silver-anchored silica nanoparticles (SSNs) as a novel antibacterial material.
      Silver nanoparticles anchored on silica nanoparticles were prepared and
      incorporated into PVA nanofibers to fabricate silver-silica embedded PVA
      nanofibers (SSN-PVA) by electrospinning. Incorporation of SSNs into PVA was
      confirmed by TEM and SEM results revealed regular nanofibers whose diameter
      increased with successive addition of SSNs. The SSN-PVA nanofibers showed
      significant antibacterial efficacy against both Gram-negative and Gram-positive
      bacteria. Our research results demonstrated SSN-embedded polymeric nanofibers can
      open up a promising prospect for the prevention of bacterial infection in diverse
      biomedical fields including wound dressing. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 106B: 1121-1128, 2018.

PMID- 28503897
TI  - Aggregate Formation of Oligonucleotides that Assist Molecular Imaging for
      Tracking of the Oxygen Status in Tumor Tissue.
AB  - The use of DNA aggregates could be a promising strategy for the molecular imaging
      of biological functions. Herein, phosphorescent oligodeoxynucleotides were
      designed with the aim of visualizing oxygen fluctuation in tumor cells. DNA
      ruthenium conjugates (DRCs) that consisted of oligodeoxynucleotides, a
      phosphorescent ruthenium complex, a pyrene unit for high oxygen responsiveness,
      and a nitroimidazole unit as a tumor-targeting unit were prepared. In general,
      oligonucleotides have low cell permeability because of their own negative
      charges; however, the DRC formed aggregates in aqueous solution due to the
      hydrophobic pyrene and nitroimidazole groups, and smoothly penetrated the
      cellular membrane to accumulate in tumor cells in a hypoxia-selective manner. The
      oxygen-dependent phosphorescence of DRC in cells was also observed. In vivo
      experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue
      that was transplanted into the left leg of mice, and showed that oxygen
      fluctuations in tumor tissue could be monitored by tracking of the
      phosphorescence emission of DRC.

PMID- 28503898
TI  - Evaluation of initial setup errors of two immobilization devices for lung
      stereotactic body radiation therapy (SBRT).
AB  - The aim of this study was to investigate the accuracy and efficacy of two
      commonly used commercial immobilization systems for stereotactic body radiation
      therapy (SBRT) in lung cancer. This retrospective study assessed the efficacy and
      setup accuracy of two immobilization systems: the Elekta Body Frame (EBF) and the
      Civco Body Pro-Lok (CBP) in 80 patients evenly divided for each system. A cone
      beam CT (CBCT) was used before each treatment fraction for setup correction in
      both devices. Analyzed shifts were applied for setup correction and CBCT was
      repeated. If a large shift (>5 mm) occurred in any direction, an additional CBCT
      was employed for verification after localization. The efficacy of patient setup
      was analyzed for 105 sessions (48 with the EBF, 57 with the CBP). Result
      indicates that the CBCT was repeated at the 1st treatment session in 22.5% and
      47.5% of the EBF and CBP cases, respectively. The systematic errors {left-right
      (LR), anterior-posterior (AP), cranio-caudal (CC), and 3D vector shift: (LR2 +
      AP2 + CC2 )1/2 (mm)}, were {0.5 +/- 3.7, 2.3 +/- 2.5, 0.7 +/- 3.5, 7.1 +/- 3.1}
      mm and {0.4 +/- 3.6, 0.7 +/- 4.0, 0.0 +/- 5.5, 9.2 +/- 4.2} mm, and the random
      setup errors were {5.1, 3.0, 3.5, 3.9} mm and {4.6, 4.8, 5.4, 5.3} mm for the EBF
      and the CBP, respectively. The 3D vector shift was significantly larger for the
      CBP (P < 0.01). The setup time was slightly longer for the EBF (EBF: 15.1 min,
      CBP: 13.7 min), but the difference was not statistically significant. It is
      concluded that adequate accuracy in SBRT can be achieved with either system if
      image guidance is used. However, patient comfort could dictate the use of CBP
      system with slightly reduced accuracy.

PMID- 28503899
TI  - Effects of maternal treatment with beta-hydroxy-beta-metylbutyrate and 2
      oxoglutaric acid on femur development in offspring of minks of the standard dark
      brown type.
AB  - The aim of the study was to evaluate the effect of the diet, mother type and sex
      of the offspring on the mechanical and geometric parameters of long bones as well
      as bone tissue density in minks. Primiparous and multiparous dams were
      supplemented with beta-hydroxy beta-methylbutyrate (a metabolite of leucine, at
      the daily dosage of 0.02 g/kg of body weight) and/or 2-oxoglutaric acid (a
      precursor of glutamine, at the daily dosage of 0.4 g/kg of body weight) during
      gestation. The diet did not influence bone tissue density and the length of the
      humerus. An increase in the length of the femur was noted in male offspring
      delivered by multiparous dams. The diet resulted in an increase in the weight of
      the humerus in males from multiparous dams and a decrease in offspring from
      primiparous dams. Heavier femora were noted in male offspring delivered by both
      types of dams. The maximum elastic strength of the humerus was higher in the
      offspring delivered by multiparous than primiparous dams, irrespective of the
      offspring sex. The diet resulted in reduction in the ultimate strength of the
      femur in the male offspring delivered by primiparous dams. Only females born by
      multiparous dams, irrespective of the diet, showed a significant increase in the
      cross-sectional area of the humerus, while a significant decline was noted in
      males delivered by multiparous dams and in all the offspring delivered by
      primiparous dams. An increase in the cross-sectional area of the femur was noted
      in the offspring delivered by multiparous dams, while reduction was observed in
      the offspring delivered by primiparous dams. These results have shown for the
      first time that the presence of beta-hydroxy-beta-methylbutyrate or 2-oxoglutaric
      acid in the diet of pregnant primiparous or multiparous dams unambiguously
      affects the geometry and mechanical properties of offspring's long bones.

PMID- 28503900
TI  - Effects of in ovo feeding of L-arginine on the development of digestive organs,
      intestinal function and post-hatch performance of broiler embryos and hatchlings.
AB  - This study was to investigate the effects of in ovo feeding (IOF) L-arginine
      (Arg) solution on the development of digestive organs, the duodenal mucosa of
      broiler embryos and hatchlings, and the growth performance of chicks during the
      first week post-hatch. A total of 720 fertilized eggs with similar weight were
      randomly allocated to three groups, consisting of eight replicates of 30 eggs
      each. Three treatments were arranged as non-injected control, diluent-injected
      (0.75% NaCl solution) group and Arg solution-injected group containing 1% Arg,
      dissolved in diluent. At 17.5 days of incubation, 0.6 ml of IOF solution was
      injected into amniotic fluid of each egg of injected groups. Results showed IOF
      of Arg solution increased (p < .05) the chick embryo weight at 19 days of
      incubation; the body weight gain of post-hatch broilers during 1-7 days; the
      weights of liver, pancreas, proventriculus and gizzard; the concentrations of
      duodenal ghrelin, vasoactive intestinal peptide and glucagon-like peptide 2; and
      the duodenum mucosal enzyme activities of alkaline phosphatase, maltase, sucrase
      and inducible nitric oxide synthase of 7-day-old post-hatch broilers compared
      with other groups. The IOF of Arg solution also increased (p < .05) the villus
      height (VH) and the ratio of VH to crypt depth (CD) and decreased (p < .05) the
      CD in duodenum of broiler embryos and post-hatch hatchlings, except for the CD at
      19 days of incubation. In conclusion, IOF of 1% Arg solution into the amnion at
      17.5 days of incubation could improve the development of digestive organs, the
      duodenal morphology, the releasing of gastrointestinal hormones and mucosal
      enzyme activities of broiler embryos and hatchlings and finally the growth
      performance of chicks during the first week post-hatch. Therefore, IOF of
      appropriate Arg solution could be an effective technology for regulating early
      nutrition supply and subsequent growth development in poultry industry.

PMID- 28503901
TI  - Thermoluminescence properties of Eu-doped and Eu/Dy-codoped Sr2 Al2 SiO7
      phosphors.
AB  - We report the thermoluminescence properties of Sr1.96 Al2 SiO7 :Eu0.04 and Sr1.92
      Al2 SiO7 :Eu0.04 Dy0.04 phosphors. These phosphors were prepared by a high
      temperature solid-state reaction method. The prepared phosphors were
      characterized by X-ray diffraction. A 254 nm source was used for ultraviolet (UV)
      irradiation and a 60 Co source was used for gamma-irradiation. The effect of
      heating rate and UV-exposure were examined. The thermoluminescence temperature
      shifts to higher values with increasing heating rate and thermoluminescence
      intensity increases with increasing UV exposure time. The trapping parameters
      such as activation energy (E), order of kinetics and frequency factor (s) were
      calculated by peak shape method. The effect of gamma- and UV-irradiation on
      thermoluminescence studies was also examined.

PMID- 28503902
TI  - Electrochemical and biocompatibility examinations of high-pressure torsion
      processed titanium and Ti-13Nb-13Zr alloy.
AB  - The purpose of this study was to estimate the electrochemical behavior and
      biocompatibility of ultrafine-grained (UFG) commercially pure titanium (CPTi) and
      Ti-13Nb-13Zr (TNZ) alloy obtained by high-pressure torsion process.
      Electrochemical behavior of materials in artificial saliva at 37 degrees C was
      evaluated by potentiodynamic polarization tests and electrochemical impedance
      spectroscopy (EIS), and the obtained results indicated that UFG TNZ alloy showed
      corrosion current density (jcorr  = 53 +/- 5 nA cm-2 ) which was 2 times lower
      compared to coarse-grained (CG) TNZ alloy (jcorr  = 110 +/- 12 nA cm-2 ) and
      higher corrosion resistance, while UFG CPTi and CPTi showed approximately the
      same corrosion rate (mean jcorr ~ 38-40 nA cm-2 ). Static immersion test in
      artificial saliva, performed in this study, showed that the released ion
      concentrations from UFG materials were more than 10 times lower than the
      permitted concentration (the highest released Ti ion concentration from UFG CPTi
      and UFG TNZ alloy was 1.12 and 1.28 ppb, respectively, while permitted
      concentration was 15.5 ppb). The in vitro cytotoxicity tests, as the initial
      phase of the biocompatibility evaluation, showed that the fraction of surviving
      cells in all examined materials was much higher compared to the control sample
      and hence demonstrated absence of cytotoxicity and an increase of fibroblast
      cells adhesion on UFG materials surfaces. UFG CPTi and UFG TNZ alloy can be
      considered as promising materials for applications in dentistry due to high
      corrosion resistance and outstanding biocompatibility which were shown in this
      study. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
      106B: 1097-1107, 2018.

PMID- 28503903
TI  - The 23rd Annual Prostate Cancer Foundation Scientific Retreat report.
AB  - INTRODUCTION: The 23rd Annual Prostate Cancer Foundation (PCF) Scientific Retreat
      was convened October 27-29, 2016, in Carlsbad, CA. METHODS: This event focuses on
      the latest advances in basic, translational, and clinical prostate cancer
      research with the greatest promise for advancing our understanding of prostate
      cancer biology and improving patient outcomes and quality of life. RESULTS:
      Themes highlighted at this year's meeting included: i) targeting DNA repair
      deficiency in prostate cancer; ii) optimizing the use of Radium-223 and bone
      targeting agents; iii) advances in cancer immunotherapeutic approaches; iv)
      targeting developmental pathways in prostate cancer; v) advances in circulating
      tumor DNA technology and applications; vi) precision survivorship; and vii) novel
      treatments and treatment strategies in prostate cancer. DISCUSSION: This article
      reviews the key advances discussed at the Retreat for the purpose of
      disseminating this knowledge to accelerate the development of new treatments and
      improved outcomes for men suffering with prostate cancer.

PMID- 28503905
TI  - Widespread hybridization within mound-building wood ants in Southern Finland
      results in cytonuclear mismatches and potential for sex-specific hybrid
      breakdown.
AB  - Hybridization and gene flow between diverging lineages are increasingly
      recognized as common evolutionary processes, and their consequences can vary from
      hybrid breakdown to adaptive introgression. We have previously found a population
      of wood ant hybrids between Formica aquilonia and F. polyctena that shows
      antagonistic effects of hybridization: females with introgressed alleles show
      hybrid vigour, whereas males with the same alleles show hybrid breakdown. Here,
      we investigate whether hybridization is a general phenomenon in this species pair
      and analyse 647 worker samples from 16 localities in Finland using microsatellite
      markers and a 1200-bp mitochondrial sequence. Our results show that 27 sampled
      nests contained parental-like gene pools (six putative F. polyctena and 21
      putative F. aquilonia) and all remaining nests (69), from nine localities,
      contained hybrids of varying degrees. Patterns of genetic variation suggest these
      hybrids arise from several hybridization events or, instead, have backcrossed to
      the parental gene pools to varying extents. In contrast to expectations, the
      mitochondrial haplotypes of the parental species were not randomly distributed
      among the hybrids. Instead, nests that were closer to parental-like F. aquilonia
      for nuclear markers preferentially had F. polyctena's mitochondria and vice
      versa. This systematic pattern suggests there may be underlying selection
      favouring cytonuclear mismatch and hybridization. We also found a new hybrid
      locality with strong genetic differences between the sexes similar to those
      predicted under antagonistic selection on male and female hybrids. Further
      studies are needed to determine the selective forces that act on male and female
      genomes in these newly discovered hybrids.

PMID- 28503906
TI  - More Than Words: The Role of Multiword Sequences in Language Learning and Use.
AB  - The ability to convey our thoughts using an infinite number of linguistic
      expressions is one of the hallmarks of human language. Understanding the nature
      of the psychological mechanisms and representations that give rise to this unique
      productivity is a fundamental goal for the cognitive sciences. A long-standing
      hypothesis is that single words and rules form the basic building blocks of
      linguistic productivity, with multiword sequences being treated as units only in
      peripheral cases such as idioms. The new millennium, however, has seen a shift
      toward construing multiword linguistic units not as linguistic rarities, but as
      important building blocks for language acquisition and processing. This shift
      which originated within theoretical approaches that emphasize language learning
      and use-has far-reaching implications for theories of language representation,
      processing, and acquisition. Incorporating multiword units as integral building
      blocks blurs the distinction between grammar and lexicon; calls for models of
      production and comprehension that can accommodate and give rise to the effect of
      multiword information on processing; and highlights the importance of such units
      to learning. In this special topic, we bring together cutting-edge work on
      multiword sequences in theoretical linguistics, first-language acquisition,
      psycholinguistics, computational modeling, and second-language learning to
      present a comprehensive overview of the prominence and importance of such units
      in language, their possible role in explaining differences between first- and
      second-language learning, and the challenges the combined findings pose for
      theories of language.

PMID- 28503907
TI  - Proteomics analysis for asymmetric inheritance of preexisting proteins between
      mother and daughter cells in budding yeast.
AB  - In budding yeast, a mother cell can produce a finite number of daughter cells
      over its life. The accumulation of a variety of types of damaged components has
      an impact on the aging process. Asymmetrical inheritance during cell division
      causes these aberrant intracellular constituents to be retained in mother cells
      and prevents them from segregating to daughter cells. However, the understanding
      of asymmetrical inheritance of individual proteins that are damaged or old age,
      and their relevance to the aging process, has been limited. The aim of this study
      is to propose a proteomics strategy for asymmetrical inheritance of preexisting
      proteins between mother and daughter cells. During synchronous culture for one
      generation, newly synthesized proteins were labeled with stable isotope amino
      acids to discriminate preexisting proteins originally expressed in mother cells,
      followed by separation of mother and daughter cells using a conventional method
      based on biotin labeling. Isotope incorporation ratios for individual proteins
      were quantified using mass spectrometry. We successfully identified 21 proteins
      whose preexisting versions were asymmetrically inherited in mother cells,
      including plasma membrane transporter involved in the aging process and organelle
      anchoring proteins related to the stress response to misfolded proteins. Thus,
      our approach would be useful for making catalog of asymmetrically inherited
      proteins.

PMID- 28503908
TI  - Microheterogeneity in imidazolium and piperidinium cation-based ionic liquids: 1D
      and 2D NMR studies.
AB  - Existence of microheterogeneity of imidazolium and piperidinium cation-based
      ionic liquids (ILs) containing PF6 and NTf2 anions has been investigated by 1D
      and 2D NMR spectroscopy. 2D NMR (especially NOESY and HOESY) has been employed
      for studying the interactions present between cation and anion as well as the
      intermolecular interaction among cations. HOESY spectrum shows that fluorine of
      anion ( PF6- and NTf2-) significantly interacts with proton of the cations.
      Combined results of HOESY and NOESY for imidazolium IL indicate that the PF6- and
      imidazolium cation are distributed in organized manner, resulting a heterogeneous
      environment in liquid state. We have also observed existence of heterogeneous
      environment for piperidinium cation-based ILs which is different from imidazolium
      ILs. It appears that existence of microheterogeneity in IL is ubiquitous and
      therefore open up the ILs field to revisit. Copyright (c) 2017 John Wiley & Sons,
      Ltd.

PMID- 28503904
TI  - White matter compromise in autism? Differentiating motion confounds from true
      differences in diffusion tensor imaging.
AB  - Common findings from diffusion tensor imaging (DTI) in autism spectrum disorder
      (ASD) include reduced fractional anisotropy (FA), and increased mean and radial
      diffusivity (MD, RD) of white matter tracts. However, findings may be confounded
      by head motion. We examined how group-level motion matching affects DTI
      comparisons between ASD and typically developing (TD) groups. We included 57 ASD
      and 50 TD participants, comparing three subsets at increasing levels of motion
      matching stringency: full sample (FS); quality-controlled (QC); and
      quantitatively-matched (QM). Groups were compared on diffusivity measures using
      Tract-Based Spatial Statistics (TBSS) and probabilistic tractography. Two methods
      for estimating diffusivity were compared: dti-fit and restore. TBSS: In set FS,
      FA was reduced in the ASD compared to the TD group throughout the right
      hemisphere. This effect was less extensive in set QC and absent in set QM.
      However, effect sizes remained stable or increased with better quality-control in
      some regions. Tractography: In set QM, MD was significantly higher in ASD overall
      and RD was higher in bilateral ILF. Effects were more robust in QM than in FS or
      QC sets. Effect sizes in several tracts increased with stringent quality
      matching. Restore improved tensor estimates, with some increases in effect sizes,
      but did not fully compensate for reduced quality. Findings suggest that some
      previously reported DTI findings for ASD may have been confounded by motion.
      However, effects in the tightly matched subset indicate that tract-specific
      anomalies probably do exist in ASD. Our results highlight the need for careful
      quality-control and motion-matching. Autism Res 2017, 10: 1606-1620. (c) 2017
      International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 28503909
TI  - Genetic risk score and cardiovascular mortality in a southern european population
      with coronary artery disease.
AB  - : Several genetic risk scores (GRS) have been associated with cardiovascular
      disease; their role, however, in survival from proven coronary artery disease
      (CAD) have yielded conflicting results. OBJECTIVE: The objective of this study
      was to evaluate long-term cardiovascular mortality according to the genetic risk
      score in a Southern European population with CAD. METHODS: A cohort of 1464 CAD
      patients with angiographic proven CAD were followed up prospectively for up to
      58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide
      polymorphisms previously associated with CAD was performed using oligonucleotides
      probes marked with fluorescence for each allele. GRS was constructed according to
      the additive model assuming codominance and categorised using the median (=26).
      Cox Regression analysis was performed to determine independent multivariate
      predictors of cardiovascular mortality. Kaplan-Meier survival curves compared
      high vs low GRS using log-rank test. C-index was done for our population, as a
      measure of discrimination in survival analysis model. RESULTS: During a mean
      follow-up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes.
      High GRS (>=26) was associated with reduced cardiovascular survival. Survival
      analysis with Cox regression model adjusted for 8 variables showed that high GRS,
      dyslipidemia, diabetes and 3-vessel disease were independent risk factors for
      cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004;
      HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival
      probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6;
      P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival
      model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease,
      stable angina and dual antiplatelet therapy. CONCLUSIONS: Besides the classical
      risk factors management, this work highlights the relevance of the genetic
      profile in survival from CAD. It is expected that new therapies will be dirsected
      to gene targets with proven value in cardiovascular survival.

PMID- 28503911
TI  - Community football teams for people with intellectual disabilities in secure
      settings: "They take you off the ward, it was like a nice day, and then you get
      like medals at the end".
AB  - BACKGROUND: People with learning disabilities (LD) are particularly vulnerable to
      mental health and behavioural difficulties, and it has been shown that regular
      exercise can improve psychosocial well-being as well as physical fitness. This
      research aims to explore the experiences of men with LD detained in secure
      settings who have engaged in community football training programmes and identify
      the benefits of such provision. METHOD: Interviews were conducted with eight
      patients in a forensic LD service, discussing their experiences of participating
      in community football. Template analysis was undertaken on the transcripts.
      RESULTS: Two master themes were identified: physical fitness and psychosocial
      benefits. As the analysis progressed, new emerging themes were identified around
      role identity and achievement, as well as extending and refining some of the
      themes from the original template including fun and belonging. Some anticipated
      themes were removed from the template entirely. CONCLUSION: The psychosocial
      benefits of organised community sports programmes far outweigh the physical
      health benefits. Careful consideration must be given to where on a treatment and
      rehabilitation pathway non-traditional therapeutic interventions such as sports
      programmes are offered as an adjunct to specific risk reduction interventions for
      people with LD in secure settings.

PMID- 28503913
TI  - Dual-fluorophore Raspberry-like Nanohybrids for Ratiometric pH Sensing.
AB  - We report on the development of raspberry-like silica structures formed by the
      adsorption of 8-hydroxypyrene-1,3,6-trisulfonate (HPTS)@silica nanoparticles
      (NPs) on rhodamine B isothiocyanate (RBTIC)@silica NPs for ratiometric
      fluorescence-based pH sensing. To overcome the well-known problem of dye leaching
      which occurs during encapsulation of anionic HPTS dye in silica NPs, we utilized
      a polyelectrolyte-assisted incorporation of the anionic HPTS. The morphological
      and optical characterization of the as-synthesized dye-doped NPs and the
      resulting nanohybrids were carried out. The pH-sensitive dye, HPTS, incorporated
      in the HPTS-doped silica NPs provided a pH-dependent fluorescence response while
      the RBITC-doped silica provided the reference signal for ratiometric sensing. We
      evaluated the effectiveness of the nanohybrids for pH sensing; the ratio of the
      fluorescence emission intensity at 510 nm and 583 nm at excitation wavelengths of
      454 nm and 555 nm, respectively. The results showed a dynamic response in the
      acidic pH range. With this approach, nanohybrids containing different dyes or
      receptors could be developed for multifunctioning and multiplexing applications.

PMID- 28503910
TI  - Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism
      spectrum disorder and autistic traits and the origin of mutations.
AB  - The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs)
      in autism spectrum disorders (ASDs) remain unclear. In this study of the whole
      exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248
      putative pSNMs in children and 285 de novo SNPs in children with detectable
      parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate
      of 51%. Analyses of validated pSNMs revealed that missense/loss-of-function (LoF)
      pSNMs with a high mutant allele fraction (MAF>= 0.2) contributed to ASD diagnoses
      (P = 0.022, odds ratio [OR] = 5.25), whereas missense/LoF pSNMs with a low MAF
      (MAF<0.2) contributed to autistic traits in male non-ASD siblings (P = 0.033).
      LoF pSNMs in parents were less likely to be transmitted to offspring than neutral
      pSNMs (P = 0.037), and missense/LoF pSNMs in parents with a low MAF were
      transmitted more to probands than to siblings (P = 0.016, OR = 1.45). We
      estimated that pSNMs in probands or de novo mutations inherited from parental
      pSNMs increased the risk of ASD by approximately 6%. Adding pSNMs into the
      transmission and de novo association test model revealed 13 new ASD risk genes.
      These results expand the existing repertoire of genes involved in ASD and shed
      new light on the contribution of genomic mosaicisms to ASD diagnoses and autistic
      traits.

PMID- 28503914
TI  - A Pd@Zeolite Catalyst for Nitroarene Hydrogenation with High Product Selectivity
      by Sterically Controlled Adsorption in the Zeolite Micropores.
AB  - The adsorption of molecules on metal nanoparticles can be sterically controlled
      through the use of zeolite crystals, which enhances the product selectivity in
      hydrogenations of reactants with more than one reducible group. Key to this
      success was the fixation of Pd nanoparticles inside Beta zeolite crystals to form
      a defined structure (Pd@Beta). In the hydrogenation of substituted nitroarenes
      with multiple reducible groups as a model reaction, the Pd@Beta catalyst
      exhibited superior selectivity for hydrogenation of the nitro group,
      outperforming both conventional Pd nanoparticles supported on zeolite crystals
      and a commercial Pd/C catalyst. The extraordinary selectivity of Pd@Beta was
      attributed to the sterically selective adsorption of the nitroarenes on the Pd
      nanoparticles controlled by the zeolite micropores, as elucidated by competitive
      adsorption and adsorbate displacement tests. Importantly, this strategy is
      general and was extended to the synthesis of selective Pt and Ru catalysts by
      fixation inside Beta and mordenite zeolites.

PMID- 28503912
TI  - High burden of metabolic comorbidities in a citywide cohort of HIV outpatients:
      evolving health care needs of people aging with HIV in Washington, DC.
AB  - OBJECTIVES: With the increasing impact of cardiovascular disease among
      populations aging with HIV, contemporary prevalence estimates for predisposing
      metabolic comorbidities will be important for guiding the provision of relevant
      lifestyle and pharmacological interventions. We estimated the citywide prevalence
      of hypertension, type 2 diabetes, dyslipidaemia, and obesity; examined
      differences by demographic subgroups; and assessed clinical correlates. METHODS:
      Utilizing an electronic medical record (EMR) database from the DC Cohort study -
      a multicentre prospective cohort study of HIV-infected outpatients - we assessed
      the period prevalence of metabolic comorbidities between 2011 and 2015 using
      composite definitions that incorporated diagnoses, pharmacy records, and
      clinical/laboratory results. RESULTS: Of 7018 adult patients (median age 50
      years; 77% black), 50% [95% confidence interval (CI) 49-51] had hypertension, 13%
      (95% CI: 12-14) had diabetes, 48% (95% CI: 47-49) had dyslipidaemia, and 35% (95%
      CI: 34-36) had obesity. Hypertension was more prevalent among black patients,
      diabetes and obesity were more prevalent among female and black patients,
      dyslipidaemia was more prevalent among male and white patients, and comorbidities
      were more prevalent among older patients (all P < 0.001). For many patients,
      evidence of treatment for these comorbidities was not available in the EMR.
      Longer time since HIV diagnosis, greater duration of antiretroviral treatment,
      and having controlled immunovirological parameters were associated with metabolic
      comorbidities. CONCLUSIONS: These findings underscore the pervasive burden of
      metabolic comorbidities among HIV-infected persons, serve as the basis for future
      analyses characterizing their impact on subsequent adverse cardiovascular
      outcomes, and highlight the need for an increased focus on the prevention and
      control of comorbid complications in this population.

PMID- 28503915
TI  - Dual therapy with a combination of unboosted atazanavir and lamivudine as
      maintenance treatment in virologically suppressed HIV-1-infected patients.

PMID- 28503916
TI  - Exploratory study of the association of volumetric modulated arc therapy (VMAT)
      plan robustness with local failure in head and neck cancer.
AB  - This work is to show which is more relevant to cause local failures (LFs) due to
      patient setup uncertainty between the planning target volume (PTV) underdosage
      and the potential target underdosage subject to patient setup uncertainties in
      head and neck (H&N) cancer treated with volumetric-modulated arc therapy (VMAT).
      Thirteen LFs in 10 H&N patients treated by VMAT were analyzed. Measures have been
      taken to minimize the chances of insufficient target delineation for these
      patients and the patients were clinically determined to have LF based on the
      PET/CT scan results by an experienced radiologist and then reviewed by a second
      experienced radiation oncologist. Two methods were used to identify the possible
      locations of LF due to underdosage: (a) examining the standard VMAT plan, in
      which the underdosed volume in the nominal dose distribution (UVN) was generated
      by subtracting the volumes receiving the prescription doses from PTVs, and (b)
      plan robustness analysis, in which in addition to the nominal dose distribution,
      six perturbed dose distributions were created by translating the CT iso-center in
      three cardinal directions by the PTV margin. The coldest dose distribution was
      represented by the minimum of the seven doses in each voxel. The underdosed
      volume in the coldest dose distribution (UVC) was generated by subtracting the
      volumes receiving the prescription doses in the coldest dose distribution from
      the volumes receiving the prescription doses in the nominal dose distribution.
      UVN and UVC were subsequently examined for spatial association with the locations
      of LF. The association was tested using the binominal distribution and the
      Fisher's exact test of independence. We found that of 13 LFs, 11 were associated
      with UVCs (P = 0.011), while three were associated with UVNs (P = 0.99). We
      concluded that the possible target underdosage due to patient setup uncertainties
      appeared to be a more relevant factor associated with LF in VMAT for H&N cancer
      than the compromised PTV coverage at least for the patients included in this
      study.

PMID- 28503917
TI  - A Smart Flexible Zinc Battery with Cooling Recovery Ability.
AB  - Flexible batteries are essential for wearable electronic devices. To meet
      practical applications, they need to be mechanically robust and stable. However,
      strong or multiple bending may sever the interfacial contact between electrode
      and electrolyte, causing capacity fading or even battery failure. Herein we
      present a new cooling-recovery concept for flexible batteries, which involves a
      temperature-sensitive sol-gel transition behavior of the thermoreversible polymer
      hydrogel electrolyte. Once a battery has suffered from strong mechanical
      stresses, a simple cooling process can refresh the electrode-electrolyte
      interface. The energy-storage capability can be recovered with a healing
      efficiency higher than 98 %. It is believed that this study not only offers new
      valuable insights, but also opens up new perspectives to develop functional
      wearable devices.

PMID- 28503919
TI  - Gold Nanoparticle Based Hairpin-Locked-DNAzyme Probe for Amplified miRNA Imaging
      in Living Cells.
AB  - A new class of intracellular nanoprobe, termed AuNP-based hairpin-locked-DNAzyme
      probe, was developed to sense miRNA in living cells. Briefly, it consists of an
      AuNP and hairpin-locked-DNAzyme strands. In the absence of target miRNA, the
      hairpin-locked-DNAzyme strand forms a hairpin structure by intramolecular
      hybridization, which could inhibit the catalytic activity of DNAzyme strand and
      the fluorescence is quenched by the AuNP. However, in the presence of target, the
      target-probe hybridization can open the hairpin and form the active secondary
      structure in the catalytic cores to yield an "active" DNAzyme, which then cleaves
      the self-strand with the assist of Mg2+. The cleaved two shorter DNA fragments
      are separated with the target. As a result, the fluorophores are released from
      the AuNP and the fluorescence is enhanced. Meanwhile, the target is also released
      and binds to another hairpin-locked-DNAzyme strand to drive another cycle of
      activation. In such a way, the target-recycling amplification leads to
      significant signal enhancement and thus offers high detection sensitivity.

PMID- 28503920
TI  - Quantification of the Depolarization and Anisotropy of Fluorophore Stokes-Shifted
      Fluorescence, On-Resonance Fluorescence, and Rayleigh Scattering.
AB  - Fluorophores are important but optically complicated photonic materials as they
      are simultaneous photon absorbers, emitters, and scatterers. Existing studies on
      fluorophore optical properties have been focused almost exclusively on its photon
      absorption and Stokes-shifted fluorescence (SSF) with scant information on the
      fluorophore photon scattering and on-resonance fluorescence (ORF). Presented
      herein is a unified theoretical framework and experimental approach for
      quantification of the fluorophore SSF, ORF, and scattering depolarization and
      anisotropy using a combination of fluorophore UV-vis, fluorescence emission, and
      resonance synchronous spectroscopic spectral measurements. A mathematical model
      for calculating fluorophore ORF and scattering cross sections has been developed
      that uses polystyrene nanoparticles as the external reference. The fluorophore
      scattering cross section is ~10-fold smaller than its ORF counterparts for all
      the six model fluorophores, but more than 6 orders of magnitude larger than the
      water scattering cross section. Another finding is that the fluorophore ORF has a
      depolarization close to 1, while its Rayleigh scattering has zero depolarization.
      This enables the experimental separation of the fluorophore ORF and photon
      scattering features in the fluorophore resonance synchronous spectra. In addition
      to opening a new avenue for material characterization, the methods and insights
      derived from this study should be important for developing new analytical methods
      that exploit the fluorophore ORF and photon scattering properties.

PMID- 28503918
TI  - Design, Synthesis, and Structure-Activity Relationship Analysis of Thiazolo[3,2
      a]pyrimidine Derivatives with Anti-inflammatory Activity in Acute Lung Injury.
AB  - Acute lung injury (ALI) has a high lethality rate, and interleukin-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha) contribute most to tissue deterioration
      in cases of ALI. In this study, we designed and synthesized a new series of
      thiazolo[3,2-a]pyrimidine derivatives based on a previously identified lead
      compound, and we evaluated their anti-inflammatory activities. Structure-activity
      relationship studies led to the discovery of two highly potent inhibitors. The
      two promising compounds were found to inhibit lipopolysaccharide (LPS)-induced IL
      6 and TNF-alpha release in a dose-dependent manner in mouse primary peritoneal
      macrophages (MPMs). Furthermore, administration of these compounds resulted in
      lung histopathological improvements and attenuated LPS-induced ALI in vivo. Taken
      together, these data indicate that these novel thiazolo[3,2-a]pyrimidine
      derivatives could be developed as candidate drugs for the treatment of ALI.

PMID- 28503921
TI  - Fluorescent Nanoparticles with Tissue-Dependent Affinity for Live Zebrafish
      Imaging.
AB  - Carbon quantum dots (CDs) are widely investigated because of their low toxicity,
      outstanding water solubility, and high biocompatibility. Specifically,
      fluorescent CDs have attracted ever-increasing interest. However, so far, only a
      few studies have focused on assessing the fluorescence of nitrogen-doped CDs
      (N@CDs) during in vivo exposure. Here, we describe a strategy for low-cost, one
      pot synthesis of N@CDs. The low toxicity and suitability of the N@CDs for
      fluorescence imaging are validated using zebrafish (ZF) as a model. Strong
      fluorescence emission from ZF embryos and larvae confirms the distribution of
      N@CDs in ZF. The retention of N@CDs is very stable, long lasting, and with no
      detectable toxicity. The presence of a strong fluorescence at the yolk sac,
      especially in the vicinity of the intestine, suggests that a high content of
      N@CDs entered the digestive system. This indicates that N@CDs may have potential
      imaging applications in elucidating different aspects of lipoprotein and
      nutritional biology, in a ZF yolk lipid transport and metabolism model. On the
      other hand, the presence of a strong selective fluorescence at the eyes and
      melanophore strips at the trunk and tail region of ZF larvae suggests that N@CDs
      has a high melanin-binding affinity. These observations support a novel and
      revolutionary use of N@CDs as highly specific bioagents for eye and skin imaging
      and diagnosis of defects in them. N@CDs are known for their multifunctional
      applications as highly specific bioagents for various biomedical applications
      because of their exceptional biocompatibility, photostability, and selective
      affinity. These characteristics were validated in the developmental ZF model.

PMID- 28503922
TI  - Solution-Processed Highly Superparamagnetic and Conductive PEDOT:PSS/Fe3O4
      Nanocomposite Films with High Transparency and High Mechanical Flexibility.
AB  - Multifunctional films can have important applications. Transparent and flexible
      films with high conductivity and magnetic properties can be used in many areas,
      such as electromagnetic interference (EMI) shielding, magnetic switching,
      microwave absorption, and also biotechnology. Herein, novel highly conductive and
      superparamagnetic thin films with excellent transparency and flexibility have
      been demonstrated. The films were formed from a poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS; Clevios PH1000)
      aqueous solution added with iron oxide (Fe3O4) nanoparticles that have a size of
      ~20 nm by spin-coating. The PEDOT:PSS/Fe3O4 films have a high conductivity of
      1080 S/cm through treatment with methylammonium iodide in an organic solvent. The
      high-conductivity PEDOT:PSS/Fe3O4 films can also have a saturation magnetization
      of 25.5 emu/g and an EMI shielding effectiveness of more than 40 dB in the 8-12.5
      GHz (X band) frequency range. The PEDOT:PSS/Fe3O4 films have additional
      advantages, like excellent transparency, good mechanical flexibility, low cost,
      and light weight. In addition, we fabricate flexible PEDOT:PSS/Fe3O4 silk threads
      with a high magnetism and conductivity.

PMID- 28503923
TI  - Sterically Shielded Electron Transporting Material with Nearly 100% Internal
      Quantum Efficiency and Long Lifetime for Thermally Activated Delayed Fluorescent
      and Phosphorescent OLEDs.
AB  - A high triplet energy (T1) is usually taken as the prerequisite of the good
      exciton confinement of electron transporting materials (ETMs); however, there is
      usually a tradeoff with large mobility and stability. Here, we demonstrated that
      good exciton confinement can also be realized utilizing a low-T1 ETM with a
      sterically shielding low-T1 unit. Given the short-range interaction of the Dexter
      energy transfer, the large steric side groups of the low-T1 ETM can effectively
      hinder the T1 of the emitters from being quenched by increasing the
      intermolecular distance. Based on this concept, a maximum external quantum
      efficiency (EQEmax) as high as 21.3% was observed in the sky-blue thermally
      activated delayed fluorescence device using a low-T1 ETM, with the EQE remaining
      at 21.2% at 1000 cd/m2 and 17.8% at 5000 cd/m2. Further, an EQEmax as high as
      25.5%, a low turn-on voltage of 2.3 V, as well as a long T90 of over 400 h at an
      initial luminance of 5000 cd/m2 were achieved for green phosphorescent devices.
      This work highlights a viable strategy for developing high-performance ETMs,
      paving their way toward practical applications.

PMID- 28503924
TI  - Complete Prevention of Dendrite Formation in Zn Metal Anodes by Means of Pulsed
      Charging Protocols.
AB  - Zn metal as anode in rechargeable batteries, such as Zn/air or Zn/Ni, suffers
      from poor cyclability. The formation of Zn dendrites upon cycling is the key
      limiting step. We report a systematic study of the influence of pulsed
      electroplating protocols on the formation of Zn dendrites and in turn on
      strategies to completely prevent Zn dendrite formation. Because of the large
      number of variables in electroplating protocols, a scanning droplet cell
      technique was adapted as a high-throughput methodology in which a descriptor of
      the surface roughness can be in situ derived by means of electrochemical
      impedance spectroscopy. Upon optimizing the electroplating protocol by
      controlling nucleation, zincate ion depletion, and zincate ion diffusion,
      scanning electron microscopy and atomic force microscopy confirmed the growth of
      uniform and homogenous Zn deposits with a complete prevention of dendrite growth.
      The implementation of pulsed electroplating as the charging protocol for
      commercially available Ni-Zn batteries leads to substantially prolonged
      cyclability demonstrating the benefits of pulsed charging in Zn metal-based
      batteries.

PMID- 28503925
TI  - Proteomics Provides Insight into the Interaction between Mulberry and Silkworm.
AB  - Mulberry leaves have been selected as a food source for the silkworm (Bombyx
      mori) for over 5000 years. However, the interaction mechanisms of mulberry
      silkworm remain largely unknown. We explore the interaction between mulberry and
      silkworm at the protein level. Total proteins were extracted from mulberry leaves
      and silkworm feces on day 5 of the fifth larval instar and analyzed on shotgun
      liquid chromatography-tandem mass spectrometry, respectively. In total, 2076 and
      210 foliar proteins were identified from mulberry leaves and silkworm feces,
      respectively. These proteins were classified into four categories according to
      their subcellular location: chloroplast proteins, mitochondrial proteins,
      secretory-pathway proteins, and proteins of other locations. Chloroplast proteins
      accounted for 68.3% in mulberry leaves but only 23.2% in the feces. In contrast,
      secretory-pathway proteins had low abundance in mulberry leaves (7.3%) but were
      greatly enriched to the largest component in the feces (60.1%). Most of the
      foliar secretory-pathway proteins in the feces were found to be resistant to
      silkworm feeding by becoming involved in primary metabolite, proteinase
      inhibition, cell-wall remodeling, redox regulation, and pathogen-resistant
      processes. On the contrary, only six defensive proteins were identified in the
      fecal chloroplast proteins including two key proteins responsible for
      synthesizing jasmonic acid, although chloroplast proteins were the second largest
      component in the feces. Collectively, the comparative proteomics analyses
      indicate that mulberry leaves not only provide amino acids to the silkworm but
      also display defense against silkworm feeding, although the silkworm grows very
      well by feeding on mulberry leaves, which provides new insights into the
      interactions between host-plant and insect herbivores.

PMID- 28503927
TI  - Infectious complications in chronic lymphocytic leukemia- a retrospective
      analysis: single institution experience.
AB  - The aim of this study was to evaluate the incidence of a variety of infectious
      complications in patients with CLL regarding the duration of CLL and the type of
      treatment. We present the retrospective analysis of patients with CLL treated at
      our institution in years 2004-2016. We collected data about the type of
      infection, pathogenes, treatment and severity of infections surpassed in
      connection with administration treatment. In the study one hundred and ten
      patients were evaluated. The average age of patients was 61.7 years (range 34.5
      91.9 years). Fludarabine was the most widely used regimen, followed by
      bendamustine and alemtuzumab. We recorded 393 episodes of infections, of which
      114 (29%) were severe and life threatening of degree 3-5, and 279 (71%) of degree
      2. The most common infections were the upper respiratory tract infections
      together with sinusitis (45.03%), pneumonia (26.20%), CMV reactivation occured in
      8.14%, infections of the skin was in 7.6 %. Most infections have occurred with
      the administration of monoclonal antibody alemtuzumab, these patients were at
      significantly higher risk of infection [RR 2.59 (1.30 to 5.17)] than patients
      receiving obinutuzumab [RR 0.63 (0.48 to 0.82)] (p = 0.0001). On the contrary,
      the safety profile of BCR signaling pathway inhibitors was very acceptable [RR
      1.17 (0.70 - 1.96)]. The number of infections have decreased during the first 12
      months of treatment with ibrutinib. In the study group we recorded 19 deaths, 8
      (7.27%) of them were of infectious etiology. The risk of infectious complications
      is lifelong in patients with CLL, it can be minimized by early detection and
      aggressive management. Novel targeted agents used in therapy of CLL have a good
      safety profile, even the risk of infection is decreased during administration.

PMID- 28503928
TI  - Effect of intermittent feeding and oat hulls to improve phytase efficacy and
      digestive function in broiler chickens.
AB  - 1. Two trials were carried out to investigate the impact of intermittent feeding
      and oat hulls as methods to stimulate the anterior digestive tract in broiler
      chickens. 2. In Trial 1, 7-d-old broilers were placed 4 per cage in 48 cages and
      fed either ad libitum or intermittently on a diet with 50 g/kg of either oat
      hulls or cellulose, with or without 1000 FTU phytase, in a 2 * 2 * 2 factorial
      arrangement. Ad libitum fed birds had two 4-h dark periods with 1-h light in
      between, while intermittently fed birds in addition had restricted access to feed
      through four 1 h feeding bouts. 3. In Trial 2, 144 broiler chickens were divided
      amongst 12 pens which were intermittently fed on the same diets as in Trial 1 in
      a 2 * 2 factorial arrangement. At 34 d of age, after 16 h feed withdrawal, birds
      were fed for 1 h, followed by dissection of 4 birds per treatment every hour for
      9 h. Contents from different segments of the digestive tract were collected
      quantitatively to assess dry matter (DM) and starch flow. 4. In Trial 1, phytase
      improved performance and nutrient availability, while oat hulls and intermittent
      feeding improved some measures of nutrient availability. Intermittent feeding
      augmented the effect of phytase on myo-inositol hexakisphosphate (IP6)
      degradation in the anterior digestive tract. 5. In Trial 2, birds filled up their
      crop and slowly passed these contents on to lower segments of the digestive
      tract. Already 1 h after commencement of feeding, the entire length of the small
      intestine was filled with DM, and no significant changes in DM content were
      observed before 4-5 h later, when the small intestine gradually became emptied.
      The tendency for a higher initial load of DM and starch in birds without oat
      hulls seems to support the hypothesis that one important function of the gizzard
      is feed-flow regulation. 6. In conclusion, the anterior digestive tract seems to
      have an important regulative function in broiler chickens when stimulated by
      intermittent feeding or structural components. More research is needed in order
      to elucidate the role of the crop and gizzard for phytase function.

PMID- 28503930
TI  - Impact of a Plant-Based Diet and Support on Mitigating Type 2 Diabetes Mellitus
      in Latinos Living in Medically Underserved Areas.
AB  - PURPOSE: To determine the impact that a high-fiber, low-fat diet, derived from
      mostly plant-based sources, when coupled with support has upon self-management of
      type 2 diabetes mellitus in Latinos from medically underserved areas (MUAs).
      DESIGN: Experimental randomized controlled community pilot study. SETTING: Three
      community clinics in MUAs located within San Bernardino County, California.
      PARTICIPANTS: Thirty-two randomly assigned Latinos with A1C greater than 6.4: 15
      control and 17 experimental. INTERVENTION: Participants completed a 5-week
      education program. Researchers provided follow-up support for 17 randomly
      assigned experimental group participants through focus groups held at
      participating clinics-1, 3, and 6 months posteducation. MEASURES: Changes in fat
      and fiber consumption were measured using a modified Dietary Screener for Mexican
      Americans. Self-management was measured through the Self-Efficacy for Exercise
      Scale and Diabetes Quality of Life Measure. ANALYSIS: Baseline characteristics
      for both groups were analyzed using independent t tests and chi2 tests. A 2-way
      repeated-measures analysis of variance was used to analyze biometric data between
      baseline and 6 months for both groups. RESULTS: Mean A1C levels decreased from
      baseline to 6 months for both groups: control, MU1 = 9.57, MU2 = 9.49;
      experimental, MU1 = 8.53, MU2 = 7.31. CONCLUSION: The experimental group
      demonstrated a statistically significant reduction in mean A1C levels ( P = .002)
      when compared to the control group.

PMID- 28503931
TI  - Burnout among healthcare workers at L'Aquila: its prevalence and associated
      factors.
AB  - Burnout, which is now recognized as a real problem in terms of its negative
      outcome on healthcare efficiency, is a stress condition that can be increased by
      exposure to natural disasters, such as the 2009 L'Aquila earthquake. This study
      aims to evaluate burnout syndrome, its associated risk factors and stress levels,
      and the individual coping strategies among healthcare professionals at L'Aquila
      General Hospital. A cross-sectional study of 190 healthcare workers was
      conducted. There was a questionnaire for the collection of the socio-demographic,
      occupational and anamnestic data, and the Maslach Burnout Inventory, the General
      Health Questionnaire-12 items (GHQ-12) and the Brief COPE were used. The burnout
      dimensions showed high scores in Emotional Exhaustion (38.95%), in
      Depersonalization (23.68%) and in lack of Personal Accomplishment (23.16%), along
      with the presence of moderate to high levels of distress (54.21%). In addition to
      factors already known to be associated with burnout (job perception and high
      levels of distress) exposure to an earthquake emerged as a factor independently
      associated with the syndrome. Adaptive coping strategies such as religiosity
      showed a significant and negative relationship with burnout. Our research
      highlights the need for interventions directed at a reduction in workload and
      work-stressors and an improvement of adaptive coping strategies, especially in a
      post-disaster workplace.

PMID- 28503932
TI  - Maladaptive Personality Trait Models: Validating the Five-Factor Model
      Maladaptive Trait Measures With the Personality Inventory for DSM-5 and NEO
      Personality Inventory.
AB  - Eight measures have been developed to assess maladaptive variants of the five
      factor model (FFM) facets specific to personality disorders (e.g., Five-Factor
      Borderline Inventory [FFBI]). These measures can be used in their entirety or as
      facet-based scales (e.g., FFBI Affective Dysregulation) to improve the
      comprehensiveness of assessment of pathological personality. There are a limited
      number of studies examining these scales with other measures of similar traits
      (e.g., DSM-5 alternative model). The current study examined the FFM maladaptive
      scales in relation to the respective general personality traits of the NEO
      Personality Inventory-Revised and the pathological personality traits of the DSM
      5 alternative model using the Personality Inventory for DSM-5. The results
      indicated the FFM maladaptive trait scales predominantly converged with
      corresponding NEO Personality Inventory-Revised, and Personality Inventory for
      DSM-5 traits, providing further validity for these measures as extensions of
      general personality traits and evidence for their relation to the pathological
      trait model. Benefits and applications of the FFM maladaptive scales in clinical
      and research settings are discussed.

PMID- 28503929
TI  - Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque.
AB  - Effector memory T cell (TEM) responses display potent antiviral properties and
      have been linked to stringent control of simian immunodeficiency virus (SIV)
      replication. Since recurrent antigen stimulation drives the differentiation of
      CD8+ T cells toward the TEM phenotype, in this study we incorporated a persistent
      herpesviral vector into a heterologous prime/boost/boost vaccine approach to
      maximize the induction of TEM responses. This new regimen resulted in CD8+ TEM
      biased responses in four rhesus macaques, three of which controlled viral
      replication to <1,000 viral RNA copies/ml of plasma for more than 6 months after
      infection with SIVmac239. Over the course of this study, we made a series of
      interesting observations in one of these successful controller animals. Indeed,
      in vivo elimination of CD8alphabeta+ T cells using a new CD8beta-depleting
      antibody did not abrogate virologic control in this monkey. Only after its
      CD8alpha+ lymphocytes were depleted did SIV rebound, suggesting that
      CD8alphaalpha+ but not CD8alphabeta+ cells were controlling viral replication. By
      2 weeks postinfection (PI), the only SIV sequences that could be detected in this
      animal harbored a small in-frame deletion in nef affecting six amino acids. Deep
      sequencing of the SIVmac239 challenge stock revealed no evidence of this
      polymorphism. However, sequencing of the rebound virus following CD8alpha
      depletion at week 38.4 PI again revealed only the six-amino acid deletion in nef.
      While any role for immunological pressure on the selection of this deleted
      variant remains uncertain, our data provide anecdotal evidence that control of
      SIV replication can be maintained without an intact CD8alphabeta+ T cell
      compartment.

PMID- 28503934
TI  - Score Disparity Between the MMSE and the SLUMS.
AB  - BACKGROUND: Multiple brief cognitive instruments are available to assess
      cognitive impairment in older adults. However, not all instruments demonstrate
      the same effectiveness when utilized with higher educated adults. This study
      evaluates the score disparity between the Mini-Mental State Examination (MMSE)
      and the St. Louis University Mental Status (SLUMS) Examination across the
      education spectrum. It was hypothesized that individuals with more years of
      formal education would produce higher scores on both the MMSE and SLUMS. Previous
      research was conducted to create a conversion scale used to compare and convert
      the MMSE scores to SLUMS scores. This research study provides additional data to
      add to the body of knowledge regarding a conversion scale for the MMSE and SLUMS.
      METHODS: Seventy-five adults older than the age of 60 years were each
      administered the MMSE and SLUMS. RESULTS: Contrary to our hypothesis, individuals
      with more years of formal education did not produce significantly greater scores
      on the MMSE or SLUMS. Likewise, education level analyzed as a continuous measure
      was not significantly correlated with the MMSE, r(75) = -0.191, or SLUMS, r(75) =
      0.019. Interestingly, among participants with a high (but not low) education
      level, there was a marginal but significant difference in mean score between the
      MMSE (29.00 +/- 1.47) and SLUMS (27.74 +/- 3.08), t(64) = 3.70, P < .001.
      CONCLUSION: Other factors besides education may impact the performance of older
      adults on the MMSE and SLUMS, but it does appear that education level may
      moderate the score disparity between the 2 instruments. Additional studies are
      needed before using the MMSE to predict the score on the SLUMS and vice versa.

PMID- 28503935
TI  - Personality Inventory for DSM-5 (PID-5) in Clinical Versus Nonclinical
      Individuals: Generalizability of Psychometric Features.
AB  - The Personality Inventory for Diagnostic and Statistical Manual of Mental
      Disorders-Fifth Edition (PID-5) was developed for the assessment of pathological
      traits in clinical settings. However, most research on the PID-5 is derived from
      nonclinical samples. To date, the comparability and generalizability of PID-5
      constructs across nonclinical and clinical samples have not been adequately
      investigated. Therefore, we investigated the measurement invariance, five-factor
      structure, and factor correlations across clinical and nonclinical samples. The
      clinical sample ( n = 598) comprised patients with nonpsychotic disorders (81%
      women; mean age = 28.95), whereas a matched nonclinical sample ( n = 598)
      comprised community-dwelling individuals (81% women; mean age = 29.59).
      Measurement invariance was analyzed using a 13-step, two-group exploratory
      structural equation modeling approach. The results demonstrated acceptable
      psychometric properties for both samples and supported strong measurement
      invariance across the groups at the domain level.

PMID- 28503933
TI  - Highly Human Immunodeficiency Virus-Exposed Seronegative Men Have Lower Mucosal
      Innate Immune Reactivity.
AB  - Risk of HIV acquisition varies, and some individuals are highly HIV-1-exposed,
      yet, persistently seronegative (HESN). The immunologic mechanisms contributing to
      this phenomenon are an area of intense interest. As immune activation and
      inflammation facilitate disease progression in HIV-1-infected persons and
      gastrointestinal-associated lymphoid tissue is a highly susceptible site for
      transmission, we hypothesized that reduced gut mucosal immune reactivity may
      contribute to reduced HIV-1 susceptibility in HESN men with a history of numerous
      rectal sexual exposures. To test this, we used ex vivo mucosal explants from
      freshly acquired colorectal biopsies from healthy control and HESN subjects who
      were stimulated with specific innate immune ligands and inactivated whole
      pathogens. Immune reactivity was then assessed via cytokine arrays and proteomic
      analysis. Mucosal immune cell compositions were quantified via
      immunohistochemistry. We found that explants from HESN subjects produced less
      proinflammatory cytokines compared with controls following innate immune
      stimulation; while noninflammatory cytokines were similar between groups.
      Proteomic analysis identified several immune response proteins to be
      differentially expressed between HIV-1-stimulated HESN and control explants.
      Immunohistochemical examination of colorectal mucosa showed similar amounts of T
      cells, macrophages, and dendritic cells between groups. The results of this pilot
      study suggest that mucosal innate immune reactivity is dampened in HESN versus
      control groups, despite presence of similar densities of immune cells in the
      colorectal mucosa. This observed modulation of the rectal mucosal immune response
      may contribute to lower risk of mucosal HIV-1 transmission in these individuals.

PMID- 28503936
TI  - Immune responses following experimental infection with Ascaridia galli and
      necrotic enteritis in broiler chickens.
AB  - Broilers commonly suffer from necrotic enteritis (NE). Other gastrointestinal
      infectious diseases affect poultry, including nematode infections which are
      considered a re-emerging disease in barn and free-range systems. The aim of this
      study was to characterize the immune response of broilers after artificial
      infection with NE and contrast these with responses to the nematode Ascaridia
      galli and determine whether immune parameters measured during the course of
      infection can be used to distinguish infected from uninfected birds. A total of
      96 one-day-old male Ross 308 broiler chickens were used in this study. At 10 days
      of age, broilers were randomly assigned to one of the following treatment groups:
      control birds (n = 32), A. galli infected birds (n = 32), or NE infected birds (n
      = 32) and inoculated with the appropriate infective agents. The immune response
      of birds was monitored through evaluation of haematology parameters, acute phase
      protein production, and intraepithelial intestinal lymphocyte population changes
      at 11, 16, 20, and 32 days of age. T-helper cells (CD4+CD8-) increased
      significantly over time, and were significantly higher in A. galli and NE
      compared to day 10 controls. In conclusion, alpha-1 glycoprotein levels can
      distinguish birds with NE from other birds, including those infected with A.
      galli; also T-helper cell numbers can distinguish both NE and A. galli from
      uninfected birds and thirdly, 10 days post infection is the best time point to
      evaluate the bird's immune response for A. galli infections.

PMID- 28503937
TI  - Assessment of tricalcium phosphate/collagen (TCP/collagene)nanocomposite scaffold
      compared with hydroxyapatite (HA) on healing of segmental femur bone defect in
      rabbits.
AB  - Bone regeneration is an important objective in clinical practice and has been
      used for different applications. The aim of this study was to evaluate the
      effectiveness of nanocomposite tricalcium phosphate (TCP)/collagen scaffolds
      combined with hydroxyapatite scaffold for bone healing in surgery of femoral
      defects in rabbits. In this study, 45 mature male New Zealand white rabbits
      between 6 and 8 months old and weighting between 3 and 3.5 kg were examined.
      Rabbits were divided into three groups. Surgical procedures were performed after
      intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg) and
      Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter-5 mm cylinder
      bone defect was created in the femur of one of the hind limbs. After inducing the
      surgical wound, all rabbits were coloured and randomly divided into three
      experimental groups of 15 animals each. Group 1 received pure medical
      nanocomposite TCP/collagen granules, group 2 received hydroxyapatite, and third
      group was a control group which received no treatment. Histopathological
      evaluation was performed on days 15, 30, and 45 after surgery. On days 15, 30,
      and 45 after surgery, the quantity and the velocity of stages of bone formation
      at the healing site in nanocomposite TCP/collagen group were better than HA and
      control groups and the quantity of newly formed lamellar bone at the healing site
      in nanocomposite TCP/collagen group were better than onward compared with HA and
      control groups. In conclusion, it seems that TCP/collagen nanocomposite has a
      significant role in the reconstruction of bone defects and can be used as
      scaffold in bone fractures.

PMID- 28503938
TI  - Design and synthesis of 2-substituted-5-(4-trifluoromethylphenyl
      sulphonamido)benzoxazole derivatives as human GST P1-1 inhibitors.
AB  - The glutathione transferases (GSTs) are a family of widely distributed Phase II
      detoxification enzymes. GST P1-1 is frequently overexpressed in rat and human
      tumours. It is suggested that overexpression of hGST P1-1 by human tumor cells
      may play a role in resistance to cancer chemotherapy. Hence, hGST P1-1 can be a
      promising target for cancer treatment. In this study, new hGST P1-1 inhibitors, 2
      (4-substitutedphenyl/benzyl)-5-(4-trifluoromethylphenylsulphonamido) benzoxazole
      derivatives (Va-Vk) have been designed and synthesized. Surprisingly, in vitro
      hGST P1-1 enzyme inhibition studies demonstrated that all of the tested compounds
      except Vj had better activity than the reference drug EA and it is also
      correlated with the docking results. Additionally we compared the interactions
      with hGST P1-1 enzyme of newly synthesized compound Vh (bearing CF3 group) and
      previously synthesized compound 5f (bearing NO2 group). According to the docking
      results, compound Vh bound to the hGST P1-1 enzyme with a higher affinity
      compared to 5f. Therefore, we can consider that these data make a sense and can
      explain its higher activity. The compounds that obtained from this research could
      be used as scaffolds in design of new potent hGST P1-1 inhibitors useful in the
      treatment of the resistance of cancer chemotherapy.

PMID- 28503940
TI  - Matrix solid-phase dispersion as a tool for phytochemical and bioactivities
      characterisation: Crataegus oxyacantha L._A case study.
AB  - The use of a matrix solid-phase dispersion (MSPD) process to extract polyphenols
      from hawthorn (Crataegus oxyacantha L.) a deciduous shrub with an expected rich
      phytochemical profile, has been evaluated. MSPD extracts of fruits and leaves
      have an outstanding content of polyphenols, although the particular phenolic
      profile is solvent dependent. The extracts were analysed by HPLC-DAD for the
      accurate identification of the major bioactive polyphenols, some of which have
      never been described for this species. MSPD has proven to be a good alternative
      to the classic methods of obtaining natural extracts, fast and with low
      consumption of organic solvents, therefore, environmentally friendly. The
      bioactivities can be considered also very remarkable, revealing extracts with
      high levels of antioxidant activity.

PMID- 28503939
TI  - Clarification of Eponymous Anatomical Terminology: Structures Named After Dr
      Geoffrey V. Osborne That Compress the Ulnar Nerve at the Elbow.
AB  - BACKGROUND: In 1957, Dr Geoffrey Osborne described a structure between the medial
      epicondyle and the olecranon that placed excessive pressure on the ulnar nerve.
      Three terms associated with such structures have emerged: Osborne's band,
      Osborne's ligament, and Osborne's fascia. As anatomical language moves away from
      eponymous terminology for descriptive, consistent nomenclature, we find
      discrepancies in the use of anatomic terms. This review clarifies the definitions
      of the above 3 terms. METHODS: We conducted an extensive electronic search via
      PubMed and Google Scholar to identify key anatomical and surgical texts that
      describe ulnar nerve compression at the elbow. We searched the following terms
      separately and in combination: "Osborne's band," "Osborne's ligament," and
      "Osborne's fascia." A total of 36 papers were included from 1957 to 2016.
      RESULTS: Osborne's band, Osborne's ligament, and Osborne's fascia were found to
      inconsistently describe the etiology of ulnar neuritis, referring either to the
      connective tissue between the 2 heads of the flexor carpi ulnaris muscle as
      described by Dr Osborne or to the anatomically distinct fibrous tissue between
      the olecranon process of the ulna and the medial epicondyle of the humerus.
      CONCLUSIONS: The use of eponymous terms to describe ulnar pathology of the elbow
      remains common, and although these terms allude to the rich history of surgical
      anatomy, these nonspecific descriptions lead to inconsistencies. As Osborne's
      band, Osborne's ligament, and Osborne's fascia are not used consistently across
      the literature, this research demonstrates the need for improved terminology to
      provide reliable interpretation of these terms among surgeons.

PMID- 28503941
TI  - Pyrrolo[2,1-a]isoquinoline and pyrrole alkaloids from Sinomenium acutum.
AB  - Two pyrrolo[2,1-a]isoquinolines (1 and 2) and three pyrrole alkaloids (3-5),
      including three new ones, named sinopyrines A-C (1-3), were isolated from the 95%
      EtOH extract of the stems and rhizomes of Sinomenium acutum (Thumb.) Rehd. et
      Wils. The structures of the new compounds were elucidated on the basis of
      spectroscopic data. This is the first report of pyrrole-bearing natural compounds
      from the family Menispermaceae.

PMID- 28503942
TI  - Optimisation of steam distillation extraction oil from onion by response surface
      methodology and its chemical composition.
AB  - Oil extraction from onion was performed by steam distillation. Response surface
      methodology was applied to evaluate the effects of ratio of water to raw
      material, extraction time, zymolysis temperature and distillation times on yield
      of onion oil. The maximum extraction yield (1.779%) was obtained as following
      conditions: ratio of water to raw material was 1, extraction time was 2.5 h,
      zymolysis temperature was 36 degrees  and distillation time was 2.6 h. The
      experimental values agreed well with those predicted by regression model. The
      chemical composition of extracted onion oil under the optimum conditions was
      analysed by gas chromatography-mass spectrometry technology. The results showed
      that sulphur compounds, like alkanes, sulphide, alkenes, ester and alcohol, were
      the major components of onion oil.

PMID- 28503944
TI  - miR-133 involves in lung adenocarcinoma cell metastasis by targeting FLOT2.
AB  - BACKGROUND: Dysregulated microRNAs (miRNAs) reported to involve into the
      oncogenesis and progression in various human cancers. However, the roles and
      mechanism of miR-133 in lung adenocarcinoma remain largely unclear. METHODS: In
      this study, qPCR assay and western blot were used to detect the expression levels
      of miR-133, Akt and FLOT2. Luciferase reporter assay was used to identify the
      target role of miR-133 on FLOT2. The cell invasion and the migration capability
      were performed using the transwell invasion assay and wound healing assay.
      RESULTS: We found that miR-133 expression levels were downregulated in human lung
      adenocarcinoma specimens and cell lines compared with the adjacent normal tissues
      and normal human bronchial epithelial cell. miR-133 significantly suppressed
      metastasis of lung adenocarcinoma cells in vitro. Furthermore, FLOT2 (flotillin
      2) identified as a direct target of miR-133, and FLOT2 expression levels were
      inversely correlated with miR-133 expression levels in human lung adenocarcinoma
      specimens. And the restoration studies suggested FGF2 as a downstream effector of
      miR-133 which acted through Akt signalling pathway. CONCLUSIONS: Our study
      revealed the mechanism that miR-133 suppresses lung adenocarcinoma metastasis by
      targeting FLOT2 via Akt signalling pathway, implicating a potential prognostic
      biomarker and therapeutic target for lung adenocarcinoma treatment.

PMID- 28503943
TI  - Transcriptional profile of ethylene glycol monomethyl ether-induced testicular
      toxicity in rats.
AB  - To clarify the molecular mechanism of ethylene glycol monomethyl ether (EGME)
      induced testicular toxicity, the potential for EGME-related changes in transcript
      levels of genes including spermatocyte-specific genes was evaluated in the testis
      of rats given single dosing of EGME at 200, 600, or 2000 mg/kg. Furthermore, the
      contribution of decreased testicular testosterone on EGME-induced spermatocyte
      toxicity was investigated by comparing to transcriptional profile due to a
      testosterone synthesis inhibitor, ketoconazole (KET), at 30 or 300 mg/kg. EGME at
      600 mg/kg or more dose-dependently caused testicular toxicity characterized by
      degeneration and necrosis of spermatocytes at stage VII-XIV seminiferous tubules.
      The spermatocyte injury was well correlated with decreased spermatocyte-specific
      gene expression. Analysis of upstream regulators by the Ingenuity Pathways
      Analysis system suggested that up-regulation of oxidative stress, protein kinase
      activation, and histone acetylation was involved in EGME-induced spermatocyte
      toxicity. Interestingly, KET decreased testicular testosterone to a similar
      extent compared to the EGME treatment, but KET at up to 300 mg/kg did not show
      any histopathological abnormality or change in the expression of spermatocyte
      specific genes. These results suggested that the decreased testicular
      testosterone have little impact on EGME-induced spermatocyte injury. In contrast,
      KET showed trends toward increases in Hsd3b2 and Hsd17b2 mRNAs, presumably
      resulting from inhibition of androgen synthesis. Transcriptome analysis clearly
      demonstrated the differential effects of EGME and KET on androgen synthesis. In
      conclusion, EGME caused spermatocyte toxicity correlated with decreased
      expression of spermatocyte-specific genes. Furthermore, oxidative stress, protein
      kinase activation, and histone acetylation were suggested to be involved in EGME
      induced testicular toxicity.

PMID- 28503945
TI  - A new ribonucleotide from Cordyceps militaris.
AB  - One new ribonucleotide, 5'-(3''-deoxy-beta-D-ribofuranosyl)-3'-deoxyadenosine
      (1), and 14 known compounds (2-15) were isolated from an ethanol extract of
      Cordyceps militaris. The chemical structures of these compounds were determined
      from 1D and 2D NMR (1H-1H COSY, HMBC, HMQC and NOESY) and HR-ESI-MS spectra, and
      results were compared with data from the literature. The effects of all isolated
      compounds were measured on NF-kappaB activation, with compound 2 exhibiting
      significant inhibitory activity against TNF-alpha-induced NF-kappaB reporter gene
      expression in HeLa cells from 3 to 100 MUM.

PMID- 28503946
TI  - Fractional CO2 laser therapy: a new challenge for vulvovaginal atrophy in
      postmenopausal women.
AB  - OBJECTIVE: To evaluate the effects of CO2 laser in the treatment of vulvovaginal
      atrophy (VVA) in postmenopausal women. METHODS: VVA was assessed in 87
      postmenopausal women (mean age 58.6 +/- 6.9 years) before and after the
      treatment. The protocol consisted of three monthly treatments and included the
      treatment of vulva. Subjective measures included VAS (Visual Analog Scale) both
      for vaginal dryness and dyspareunia; DIVA (Day-by-day Impact of Vaginal Aging); a
      questionnaire on treatment satisfaction and one about the degree of pain during
      the procedure. Objective measures included VHI (Vaginal Health Index) and VVHI
      (Vulvo-Vaginal Health Index). Time points of the study were at the screening
      visit (T0), at baseline (T1), at week 4 (T2), at week 8 (T3), after 3 months
      since the last laser application (T4), after 6 months (T5), after 9 months (T6),
      after 12 months (T7) and after 15 months (T8). RESULTS: Treatment induced
      significant improvement in the VAS score. After treatment, VHI and VVHI indicated
      no VVA and this improvement was long lasting. Multivariate analysis showed that
      the time of follow-up was correlated with better VHI and VVHI (p < 0.001). DIVA
      improved over time (p < 0.001). CONCLUSIONS: This study shows that CO2 laser
      treatment induces a significant and long-lasting improvement of symptoms.

PMID- 28503947
TI  - Recommendations for data monitoring committees from the Clinical Trials
      Transformation Initiative.
AB  - Background/aims Use of data monitoring committees to oversee clinical trials was
      first proposed nearly 50 years ago. Since then, data monitoring committee use in
      clinical trials has increased and evolved. Nonetheless, there are no well-defined
      criteria for determining the need for a data monitoring committee, and
      considerable variability exists in data monitoring committee composition and
      conduct. To understand and describe the role and function of data monitoring
      committees, and establish best practices for data monitoring committee trial
      oversight, the Clinical Trials Transformation Initiative-a public-private
      partnership to improve clinical trials-launched a multi-stakeholder project.
      Methods The data monitoring committee project team included 16 individuals
      charged with (1) clarifying the purpose of data monitoring committees, (2)
      identifying best practices for independent data monitoring committee conduct, (3)
      describing effective communication practices, and (4) developing strategies for
      training data monitoring committee members. Evidence gathering included a survey,
      a series of focus group discussions, and a 2-day expert meeting aimed at
      achieving consensus opinions that form the foundation of our data monitoring
      committee recommendations. Results We define the role of the data monitoring
      committee as an advisor to the research sponsor on whether to continue, modify,
      or terminate a trial based on periodic assessment of trial data. Data monitoring
      committees should remain independent from the sponsor and be composed of members
      with no relevant conflicts of interest. Representation on a data monitoring
      committee generally should include at least one clinician with expertise in the
      therapeutic area being studied, a biostatistician, and a designated chairperson
      who has experience with clinical trials and data monitoring. Data monitoring
      committee meetings are held periodically to evaluate the unmasked data from
      ongoing trials, but the content and conduct of meetings may vary depending on
      specific goals or topics for deliberation. To guide data monitoring committee
      conduct and communication plans, a charter consistent with the protocol's
      research design and statistical analysis plan should be developed and agreed upon
      by the sponsor and the data monitoring committee prior to patient enrollment. We
      recommend concise and flexible charters that explain roles, responsibilities,
      operational issues, and how data monitoring committee recommendations are
      generated and communicated. The demand for data monitoring committee members
      appears to exceed the current pool of qualified individuals. To prepare a new
      generation of trained data monitoring committee members, we encourage a
      combination of didactic educational programs, practical experience, and skill
      development through apprenticeships and mentoring by experienced data monitoring
      committee members. Conclusion Our recommendations address data monitoring
      committee use, conduct, communication practices, and member preparation and
      training. Furthermore recommendations form the foundation for ongoing efforts to
      improve clinical trial oversight and enhance the safety and integrity of clinical
      research. These recommendations serve as a call to action for implementation of
      best practices that benefit study participants, study sponsors, and society.

PMID- 28503948
TI  - Attraction behaviour of Anagrus nilaparvatae to remote lemongrass (Cymbopogon
      distans) oil and its volatile compounds.
AB  - Utilisation of Anagrus nilaparvatae is a promising and effective method for
      planthoppers manipulation. Twenty-seven components of remote lemongrass
      (Cymbopogon distans) oil were identified by GC/MS and nine volatiles were
      selected for behavioural experiments. In this study, we noted that the remote
      lemongrass oil was attractive to female A. nilaparvatae at concentrations of 0.1
      and 1 mg/L. alpha-Pinene, beta-pinene, eucalyptol, carveol and D-carvone
      attracted female wasps in the dose-dependent bioassays. Blend 1 (a mixture of
      eucalyptol, D-carvone, carveol, alpha-pinene, and beta-pinene with ratios of
      remote lemongrass oil volatiles of 625:80:11:5:3) attracted female wasps at 10
      mg/L, while blend 2 (a mixture of the same five volatiles at the same loading
      ratio) attracted them at 0.1 and 1 mg/L. These results suggested that plant
      essential oils could be attractants for natural enemies to control pests. The
      ratios of volatiles in the mixtures affect the attractiveness of the synthetic
      mixtures.

PMID- 28503949
TI  - Silymarin nanoemulsion against human hepatocellular carcinoma: development and
      optimization.
AB  - OBJECTIVE: Nanoemulsion of silymarin was developed and optimized. MATERIALS AND
      METHODS: Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8%
      v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were
      used as oil phase, surfactant and co-surfactant while distilled water (65.22%
      v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of
      particle size, viscosity, electrical conductivity and refractive index. Further,
      in vitro release, in vivo pharmacokinetic study, stability study and cancer cell
      line studies were also performed. RESULTS AND DISCUSSION: The optimized
      formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity
      of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also
      showed higher AUC (p < .01) and Cmax (p < .01) and shorter Tmax (p < .05)
      compared with conventional and standard suspensions of silymarin. The stability
      study also showed considerably stable formulations at refrigerator temperature as
      compared with room temperature (p > .05). The cancer cell line studies also
      confirmed that silymarin nanoemulsion reduced the cell viability and increased
      ROS intensity and chromatin condensation (p < .05). CONCLUSION: Our results
      concluded that nanoemulsion may be an efficient carrier for oral delivery of
      silymarin against human hepatocellular carcinoma without damaging normal cells.

PMID- 28503950
TI  - The effects of rapeseed meal and legume seeds as substitutes for soybean meal on
      productivity and gastrointestinal function in rabbits.
AB  - The aim of this study was to determine the effects of soybean meal (SBM)
      substitution by a mixture of rapeseed meal (RSM), white lupine seeds (WLS) and
      pea seeds (PS) on productivity, nutrient digestibility, nitrogen retention and
      gastrointestinal function in Hyplus rabbits. The Control diet (SBM15) contained
      15% SBM, whereas Diet SBM7.5 contained 7.5% SBM, 5% RSM, 4% WLS and 3% PS. In
      Diet SBM0, SBM was completely replaced by RSM, WLS and PS (10%, 8% and 6%,
      respectively). A production trial was performed on 90 Hyplus rabbits aged from 35
      to 84 d (45 each sex; 953 +/- 4.6 g). A digestion and balance trial was conducted
      on 30 rabbits. Additionally, several parameters of the gastrointestinal tracts
      from eight animals from each group were analysed, where special attention was
      paid to the enzymatic activity of microbiota and the short-chain fatty acids
      concentration in caecum and colon. The experimental diets did not cause
      significant differences regarding performance parameters evaluated in vivo and
      post-mortem, and in the nutrient and energy digestibility or nitrogen retention.
      The observed changes in the enzymatic activity of large gut microbiota, including
      the selective increase in secretion of glycoside hydrolases by bacterial cells,
      seem to be responsible for the unchanged growth performance of rabbits fed diets
      where SBM was substituted by a mixture of RSM, WLS and PS. The obtained results
      indicate that in rabbit diets SBM may be, partially or completely, successfully
      replaced by a feed mixture of RSM, WLS and PS.

PMID- 28503951
TI  - Gold nanoparticles applications: from artificial enzyme till drug delivery.
AB  - Today, nano-medicine promotes new therapeutics and diagnostics tools, including
      sensing of biomolecules as a biosensor, cancer chemotherapy and drug or gene
      delivery. Because of small size and biocompatibility of gold nanoparticles
      (GNPs), they become a good candidate for biological application. Also, thanks to
      their biological and chemical properties, they can mimic function of some enzymes
      including super oxide dismutase (SOD), esterase, etc. Also, biomaterials and
      bioengineering have grown so fast since the last decade for many therapeutic
      applications such as tissue regeneration. Among these cutting edge technology,
      nanomaterials find the way to becoming a very powerful tool for using in many
      fields of researchers including biosensing, gene therapy and chemotherapy. In
      this review, we focused on some biological applications of GNPs in biology and
      medicine.

PMID- 28503952
TI  - Hyaluronic acid/polyethylene glycol nanoparticles for controlled delivery of
      mitoxantrone.
AB  - Hyaluronic acid (HA) has inherent ability to target the CD44 receptors and
      internalize into tumour cells via receptor-mediated endocytosis. Therefore,
      conjugation of this natural linear polysaccharide to polymeric NPs or micelles,
      as one of the most promising approaches, could be useful for future clinical
      applications such as drug delivery. Accordingly, we report on the synthesis of
      mitoxantrone (MTX)-conjugated polymeric nanoparticles (NPs) composed of
      polyethylene glycol-HA (PEG-HA) for MTX delivery toward special tumour cells. To
      determine the size of the polymeric NPs, field emission scanning electron
      microscopy (FESEM) and particle size analyzer system Zetasizer_nanoZS were
      employed. The in vitro cytotoxicity analysis of MTX-loaded HA-PEG NPs and free
      MTX against two cell lines with different levels of CD44 expression (MDA-MB-231
      (very high) and MCF-7 (low) was conducted by MTT assay. Also, computational
      molecular docking was employed to study in detail the active site residues and
      the critical interactions between HA-EDA-PEG-EDA-MTX NPs and CD44 receptor. The
      particle size analysis and electron microscopy showed the average size of
      polymeric NPs less than 350 nm. FT-IR spectrophotometry analysis and also NMR
      confirmed the conjugation of HA and MTX onto the PEG. Cytotoxicity assay revealed
      that the engineered polymeric NPs were able to specifically bind to and
      significantly inhibit the CD44 receptor-positive MDA-MB-231 cells, but not the
      CD44-negative MCF-7 cells. Furthermore, analysis of the binding modes revealed
      that for the best-docked pose nearly 10 conventional hydrogen bond can occur
      between the MTX-EDA-PEG-EDA-HA NPs and amino acids of CD44 receptor. Based on
      these findings, we suggest the HA-PEG-MTX NPs as an effective functional-targeted
      nanomedicine toward therapy of CD44-positive cancers.

PMID- 28503953
TI  - Effect of deltamethrin and fluoride co-exposure on the brain antioxidant status
      and cholinesterase activity in Wistar rats.
AB  - The study evaluated the effect of commercial preparation of deltamethrin,
      Butox(r), and fluoride (F-) co-exposure on the brain antioxidant status and
      cholinesterase activity in rats. Group A was untreated. Group B was gavaged
      Butox(r), providing deltamethrin at the dose rate of 1.28 mg per kg body weight
      per day. Group C was administered F-, as NaF, in drinking water providing 20 ppm
      F-. Group D received both deltamethrin and F- at the same dosages as groups B and
      C, respectively. Although, glutathione S-transferase activity was induced only in
      Butox(r) alone treated group, the activities of superoxide dismutase and catalase
      were inhibited in all treatment groups when compared to the control group.
      Elevated lipid peroxidation was observed in the groups exposed to F-. The
      activity of erythrocyte acetylcholinesterase (AChE) was inhibited in Butox(r)
      treated groups, whereas brain AChE activity was inhibited in all treatment
      groups. In conclusion, both deltamethrin (given as Butox(r)) and F- inhibit AChE
      activity and produce oxidative stress in brain with F- producing more oxidative
      damage. However, compared to the individual exposures, the co-exposure of these
      chemicals does not produce any exacerbated alteration in these biochemical
      parameters.

PMID- 28503954
TI  - Experiences of employment among young people with juvenile idiopathic arthritis:
      a qualitative study.
AB  - PURPOSE: This study explored expectations and experiences of employment among
      young people with juvenile idiopathic arthritis and the role of health
      professionals in promoting positive employment outcomes. METHODS: Semistructured
      interviews (n = 13) and three focus groups (n = 9, n = 4, n = 3) were conducted
      with young people (16-25 y) and adults (26-31 y) with juvenile idiopathic
      arthritis and semistructured interviews (n = 9) were conducted with health
      professionals. Transcripts were analyzed thematically. RESULTS: Young people with
      juvenile idiopathic arthritis have concerns about employers' attitudes toward
      employees with long-term health conditions and lack knowledge of
      antidiscrimination legislation. Young people not in education, employment or
      training identify arthritis as a key barrier. Challenges associated with
      arthritis (e.g., pain, psychological distress) may not be visible to employers.
      Decisions about disclosing arthritis are challenging and cause anxiety. Young
      people associate good disease management and access to flexible and convenient
      care with their capacity to succeed in employment. Psychosocial and vocational
      interventions have benefited some young people but are not routinely available.
      CONCLUSIONS: Low expectations of employers may affect young people's decisions
      about disclosure and seeking appropriate support in the work place. Health
      professionals can equip young people with knowledge and skills to negotiate
      appropriate support, through signposting to antidiscrimination information and
      offering practice of transferable skills such as disclosure in consultations.
      Implications for rehabilitation Young people with juvenile idiopathic arthritis
      encounter challenges with regard to employment; many lack the knowledge and
      skills to negotiate appropriate support from employers. Rehabilitation
      professionals could play a more substantial role in equipping them with relevant
      knowledge and skills by signposting to antidiscrimination information and
      nurturing transferable skills, such as disclosure, in consultations. Potentially
      helpful interventions, such as group activities or assessment by a psychologist,
      have benefited some but need more evaluative scrutiny with respect to employment
      outcomes.

PMID- 28503956
TI  - Sacituzumab govitecan: an antibody-drug conjugate.
AB  - INTRODUCTION: Despite advances in the diagnosis and treatment of patients with
      cancer, patients with metastatic cancer have limited therapeutic options after
      initial lines of therapy. Understanding tumor biology has translated into the
      identification of actionable targets that resulted in therapeutics. Antibody-drug
      conjugates (ADC) are capitalizing on this explosion of scientific information.
      ADCs allow an antibody to a unique target to be conjugated via an innovative
      linker, to a highly toxic drug which is delivered to its target. Sacituzumab
      govitecan is an ADC that combines the active molecule in irinotecan, SN-38, to an
      antibody targeting trop2. Areas covered: In this review, the authors introduce
      the reader to the ADC sacituzumab govitecan providing the reader with details
      about its pharmacokinetics, pharmacodynamics, efficacy and safety. The authors
      also give their expert analysis about its potential future use. Expert opinion:
      Sacituzumab govitecan is a novel and well-tolerated therapeutic showing promising
      results in difficult to treat cancers. Further studies are underway to optimize
      the group of patients that would benefit from it. Given its excellent
      performance, we are cautiously optimistic it will be approved by the FDA.

PMID- 28503955
TI  - New insights into the earliest stages of colorectal tumorigenesis.
AB  - INTRODUCTION: Tumors in the large intestine have been postulated to arise via a
      stepwise accumulation of mutations, a process that takes up to 20 years. Recent
      advances in lineage tracing and DNA sequencing, however, are revealing new
      evolutionary models that better explain the vast amount of heterogeneity observed
      within and across colorectal tumors. Areas covered: A review of the literature
      supporting a novel model of colorectal tumor evolution was conducted. The
      following commentary examines the basic science and clinical evidence supporting
      a modified view of tumor initiation and progression in the colon. Expert
      commentary: The proposed 'cancer punctuated equilibrium' model of tumor evolution
      better explains the variability seen within and across polyps of the colon and
      rectum. Small colorectal polyps (6-9mm) followed longitudinally by interval
      imaging with CT colonography have been reported to have multiple fates: some
      growing, some remaining static in size, and others regressing in size over time.
      This new model allows for this variability in growth behavior and supports the
      hypothesis that some tumors can be 'born to be bad' as originally postulated by
      Sottoriva and colleagues, with very early molecular events impacting tumor
      fitness and growth behavior in the later stages of the disease process.

PMID- 28503957
TI  - A model for developing disability confidence.
AB  - PURPOSE: Many clinicians, educators, and employers lack disability confidence
      which can affect their interactions with, and inclusion of people with
      disabilities. Our objective was to explore how disability confidence developed
      among youth who volunteered with children who have a disability. METHODS: We
      conducted 30 in-depth interviews (16 without a disability, 14 with disabilities),
      with youth aged 15-25. We analyzed our data using an interpretive, qualitative,
      thematic approach. RESULTS: We identified four main themes that led to the
      progression of disability confidence including: (1) "disability discomfort,"
      referring to lacking knowledge about disability and experiencing unease around
      people with disabilities; (2) "reaching beyond comfort zone" where participants
      increased their understanding of disability and became sensitized to difference;
      (3) "broadened perspectives" where youth gained exposure to people with
      disabilities and challenged common misperceptions and stereotypes; and (4)
      "disability confidence" which includes having knowledge of people with
      disabilities, inclusive, and positive attitudes towards them. CONCLUSIONS:
      Volunteering is one way that can help to develop disability confidence. Youth
      with and without disabilities both reported a similar process of developing
      disability confidence; however, there were nuances between the two groups.
      Implications for Rehabilitation The development of disability confidence is
      important for enhancing the social inclusion of people with disabilities.
      Volunteering with people who have a disability, or a disability different from
      their own, can help to develop disability confidence which involves positive
      attitudes, empathy, and appropriate communication skills. Clinicians, educators,
      and employers should consider promoting working with disabled people through such
      avenues as volunteering or service learning to gain disability confidence.

PMID- 28503959
TI  - Emerging drugs for prevention of T-cell mediated rejection in liver and kidney
      transplantation.
AB  - INTRODUCTION: Acute and chronic graft rejection continues to be an important
      problem after solid organ transplantation. With the introduction of potent
      immunosuppressive agents such as calcineurin inhibitors, the risk of rejection
      has been significantly reduced. However, the adverse effects of life-long
      immunosuppression remain a concern, and there exist a fine balance between over
      immunosuppression and risk of rejection. Areas covered: In this review, the
      current standard of care in immunosuppressive therapy, including the use of
      steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of
      rapamycin inhibitors, will be discussed. Newer immunosuppressive agents showing
      promising early data after liver and kidney transplantation will also be
      explored. Expert Opinion: Currently, calcineurin inhibitors continue to be a
      vital component of immunosuppressive therapy after solid organ transplantation.
      Although minimization and avoidance strategies have been developed, the ultimate
      goal of inducing tolerance remains elusive. Newer emerging agents should have
      potent and specific immunosuppressive activity, with minimal associated side
      effects. An individualized approach should be adopted to tailor immunosuppression
      according to the different needs of recipients.

PMID- 28503958
TI  - Neonatal management and outcome in alloimmune hemolytic disease.
AB  - INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal
      and neonatal erythroid cells are destroyed by maternal erythrocyte
      alloantibodies, it leads to anemia and hydrops in the fetus, and
      hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of
      intensive phototherapy and exchange transfusions to treat severe
      hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other
      postnatal complications have been reported such as thrombocytopenia, iron
      overload and cholestasis requiring specific management. Areas covered: This
      review focusses on the current neonatal management and outcome of hemolytic
      disease and discusses postnatal treatment options as well as literature on long
      term neurodevelopmental outcome. Expert commentary: Despite major advances in
      neonatal management, multiple issues have to be addressed to optimize postnatal
      management and completely eradicate kernicterus. Except for strict adherence to
      guidelines, improvement could be achieved by clarifying the epidemiology and
      pathophysiology of HDFN. Several pharmacotherapeutic agents should be further
      researched as alternative treatment options in hyperbilirubinemia, including
      immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and
      prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in
      neonates. Long-term follow-up studies are needed in HDFN, especially on
      thrombocytopenia, iron overload and cholestasis.

PMID- 28503960
TI  - Management of severe complications in Behcet's disease with TNF inhibitors.
AB  - INTRODUCTION: The efficacy of anti-TNFalpha agents has been recently evaluated in
      many studies in Behcet's disease (BD), particularly in ocular and life
      threatening manifestations such as neurological and vascular disease. Areas
      covered: The following article aims to summarize the currently available efficacy
      and safety data of anti-TNFalpha agents in BD. Expert opinion: Most studies have
      shown dramatic and rapid efficacy with anti-TNFalpha agents on the main BD
      associated issues including posterior uveitis, gastro-intestinal and neurological
      complications as well as major vessel disease. Experts in the field do recommend
      the use of anti-TNF agents (either infliximab or adalimumab) as a first-line
      therapy in severe posterior uveitis in BD and now use anti-TNFalpha treatment in
      BD-associated life threatening manifestations. However, data is mainly based on
      retrospective cohorts or open-label prospective studies. Controlled studies
      (versus conventional immunosuppressants such as azathioprine and
      cyclophosphamide) are warranted to properly evaluate their efficacy as first line
      therapeutic in life-threatening manifestations of BD.

PMID- 28503961
TI  - Psychometric properties of the neck disability index amongst patients with
      chronic neck pain using item response theory.
AB  - OBJECTIVE: The Neck Disability Index (NDI) is commonly used for clinical and
      research assessment for chronic neck pain, yet the original version of this tool
      has not undergone significant validity testing, and in particular, there has been
      minimal assessment using Item Response Theory. The goal of the present study was
      to investigate the psychometric properties of the original version of the NDI in
      a large sample of individuals with chronic neck pain by defining its internal
      consistency, construct structure and validity, and its ability to discriminate
      between different degrees of functional limitation. METHODS: This is a cross
      sectional cohort study of 585 consecutive patients with chronic neck pain seen in
      a university hospital rehabilitation clinic. Internal consistency was evaluated
      using Cronbach's alpha, construct structure was evaluated by exploratory factor
      analysis, and discrimination ability was determined by Item Response Theory.
      RESULTS: The NDI demonstrated good internal consistency assessed by Cronbach's
      alpha (0.87). The exploratory factor analysis identified only one factor with
      eigenvalue considered significant (cutoff 1.0). When analyzed by Item Response
      Theory, eight out of 10 items demonstrated almost ideal difficulty parameter
      estimates. In addition, eight out of 10 items showed high to perfect estimates of
      discrimination ability (overall range 0.8 to 2.9). CONCLUSIONS: Amongst patients
      with chronic neck pain, the NDI was found to have good internal consistency, have
      unidimensional properties, and an excellent ability to distinguish patients with
      different levels of perceived disability. Implications for Rehabilitation The
      Neck Disability Index has good internal consistency, unidimensional properties,
      and an excellent ability to distinguish patients with different levels of
      perceived disability. The Neck Disability Index is recommended for use when
      selecting patients for rehabilitation, setting rehabilitation goals, and
      measuring the outcome of intervention.

PMID- 28503962
TI  - Impact of price deregulation policy on the affordability of essential medicines
      for women's health: a panel data analysis.
AB  - BACKGROUND: A new policy which required deregulation on prices of off-patent
      medicines for women's health during procurement was introduced in China in
      September 2015. The current study examines this policy's impact on the
      affordability of essential medicines for women's health. METHODS: Based on
      product-level panel data, a fixed effect regression model is employed by using
      procurement records from Hubei Centralist Tender for Drug Purchase platform. In
      the model, Affordability was measured with prices. The Competition consists of
      two parts: generic competition and therapeutic class competition which are
      measured with generic competitors and therapeutic substitutes. Instrument
      variable is used to deal with endogeneity. RESULTS: The policy helped control
      prices of essential medicines for women's health. Generic competition helped
      control prices, however, therapeutic class competition caused higher prices.
      CONCLUSIONS: The new policy helped enhance the affordability of essential
      medicines for women's health as expected, which provides empirical evidence on
      price deregulation. Besides, generic competition is important in price control
      despite strict regulatory system in China.

PMID- 28503963
TI  - Nominal group technique for individuals with cognitive disability: a systematic
      review.
AB  - RATIONALE: Considering the perspectives of individuals with cognitive disability
      is important for their participation in their self-directed health care. The
      nominal group technique (NGT) has been identified as a method to gather opinions
      of people with cognitive disability; however, a synthesis of methodological
      considerations to undertake when employing the approach among people with
      cognitive disability is non-existent. METHOD: A systematic review guided by the
      preferred reporting items for systematic review and meta-analysis protocols was
      undertaken. Five databases (CINAHL, ISI Web of Science, ProQuest Social Science
      Journals, Scopus, and MEDLINE) were searched for peer-reviewed literature
      published before September 2016. Methodological considerations pertaining to the
      four stages of the NGT- generating ideas, recording ideas, clarification, and
      ranking - were extracted from each study. RESULTS: Nine publications contributing
      to eight studies were included. Methodological considerations focused on (i) the
      number of participants within discussion groups, (ii) research question
      introduction, (iii) support individuals and accessible methods, (iv) ranking, and
      (v) researcher training and counselling services. CONCLUSIONS: The use of the NGT
      to gain the health care perspectives of adults with cognitive disability is
      promising. Conducting nominal group techniques informed by the methodological
      considerations identified within this review can work towards ensuring that the
      health care perspectives of people with cognitive disability are considered.
      Implications for rehabilitation The emergent policy move towards self-directed
      health care for people with disability requires that the health care perspectives
      of people with disability are considered. Effective consultation and discussion
      techniques are essential to gain the health care perspectives of people with
      cognitive disability. After undertaking methodological considerations, the NGT
      can be an effective approach towards gaining the health care perspectives of
      people with cognitive disability.

PMID- 28503964
TI  - Recent advances in intensity modulated radiotherapy and proton therapy for
      esophageal cancer.
AB  - INTRODUCTION: Radiotherapy is an important component of the standard of care for
      esophageal cancer. In the past decades, significant improvements in the planning
      and delivery of radiation techniques have led to better dose conformity to the
      target volume and improved normal tissue sparing. Areas covered: This review
      focuses on the advances in radiotherapy techniques and summarizes the availably
      dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT),
      volumetric modulated arc therapy, proton therapy, and four-dimensional
      radiotherapy for esophageal cancer, and discusses the challenges and future
      development of proton therapy. Expert commentary: Although three-dimensional
      conformal radiotherapy is the standard radiotherapy technique in esophageal
      cancer, the retrospectively comparative studies strongly suggest that the
      dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can
      translate into improved clinical outcomes, despite the lack of prospective
      randomized evidence. As a novel form of conventional IMRT technique, volumetric
      modulated arc therapy can produce equivalent or superior dosimetric quality with
      significantly higher treatment efficiency in esophageal cancer. Compared with
      photon therapy, proton therapy has the potential to achieve further clinical
      improvement due to their physical properties; however, prospective clinical data,
      long-term results, and cost-effectiveness are needed.

PMID- 28503965
TI  - Prevalence of Campylobacter species in wild birds of South Korea.
AB  - Campylobacter species cause human gastrointestinal infections worldwide. They
      commonly inhabit intestines of avian species including wild birds. They might
      play a role in the spread of infections to humans and other bird species. The
      prevalence of Campylobacter species in 2164 faecal samples of wild birds
      (representing 71 species and 28 families) captured across the Korean peninsula
      was evaluated in this study. The overall prevalence was 15.3% (332/2164). Bird
      species belonging to the family Charadriidae had the highest isolation rate
      (30.0%), followed by those belonging to the families Ardeidae (26.4%), Turdidae
      (21.9%), and Anatidae (15.3%). The prevalence of Campylobacter spp. differed
      significantly according to migratory habit. Stopover birds were the most commonly
      infected (19.0%), followed by winter migratory (16.7%) and summer migratory birds
      (12.3%). However, indigenous birds showed very low prevalence (2.7%).
      Antimicrobial susceptibility tests were performed for 213 isolates. Results
      showed that Campylobacter jejuni isolates (n = 169) exhibited resistance to
      nalidixic acid (5.3%), ciprofloxacin (3.0%), and tetracycline (1.8%), while
      Campylobacter lari (n = 1) displayed resistance to nalidixic acid and
      ciprofloxacin. However, all Campylobacter coli isolates (n = 20) were susceptible
      to all antimicrobials tested. This is the first report on the prevalence of
      Campylobacter species in wild birds that seasonally or indigenously inhabit the
      Korean peninsula. Our results indicate that the overall prevalence of
      Campylobacter in wild birds is moderate. Therefore, birds might serve as
      significant reservoirs for Campylobacter pathogens.

PMID- 28503966
TI  - Topical use of dexpanthenol: a 70th anniversary article.
AB  - Approximately 70 years ago, the first topical dexpanthenol-containing formulation
      (BepanthenTM Ointment) has been developed. Nowadays, various topical dexpanthenol
      preparations exist, tailored according to individual requirements. Topical
      dexpanthenol has emerged as frequently used formulation in the field of
      dermatology and skin care. Various studies confirmed dexpanthenol's moisturizing
      and skin barrier enhancing potential. It prevents skin irritation, stimulates
      skin regeneration and promotes wound healing. Two main directions in the use of
      topical dexpanthenol-containing formulations have therefore been pursued: as skin
      moisturizer/skin barrier restorer and as facilitator of wound healing. This 70th
      anniversary paper reviews studies with topical dexpanthenol in skin conditions
      where it is most frequently used. Although discovered decades ago, the exact
      mechanisms of action of dexpanthenol have not been fully elucidated yet. With the
      adoption of new technologies, new light has been shed on dexpanthenol's mode of
      action at the molecular level. It appears that dexpanthenol increases the
      mobility of stratum corneum molecular components which are important for barrier
      function and modulates the expression of genes important for wound healing. This
      review will update readers on recent advances in this field.

PMID- 28503968
TI  - The Five Stages of Prisoner Reentry: Toward a Process Theory.
AB  - This article is based on an ethnographic study involving 58 Roma and Romanian
      participants who were released from Jilava Prion in Romania between January and
      July 2015. The methodology involved interviews, observation, questionnaires, and
      photovoice. The findings seem to suggest that most of the factors associated with
      desistance and reentry in the literature are relevant to the ex-prisoner's
      experiences. The main contribution of this article is the observation that these
      factors come into play at different times and in different stages of the reentry
      process. Five reentry stages were identified in this study: prerelease
      anticipation, recovery and reunion, activation, consolidation, and relapse. The
      aim of the article is to describe this reentry process as the participants
      experienced it. Theoretical and practice implications are discussed.

PMID- 28503967
TI  - Cytotoxic and cytoprotective effects of tryptamine-4,5-dione on neuronal cells: a
      double-edged sword.
AB  - Serotonin (5-hydroxytryptamine) is a putative substrate for myeloperoxidase,
      which may convert it into the reactive quinone tryptamine-4,5-dione (TD). In this
      study, we found that the viability of human SH-SY5Y neuroblastoma cells treated
      with 25 MUM TD was increased to approximately 117%. On the other hand, the cell
      viability was significantly decreased by exposure to TD (150-200 MUM), with an
      increase in intracellular reactive oxygen species (ROS). Interestingly, pre
      treatment of SH-SY5Y cells with 100 MUM TD prevented cell death and suppressed
      intracellular ROS generation evoked by the addition of hydrogen peroxide (H2O2).
      Expression of the phase-II antioxidant enzyme NAD(P)H: quinone oxidoreductase 1
      and haem oxygenase 1 were upregulated by TD at a concentration of 50-100 MUM.
      Nuclear factor erythroid 2-related factor 2 (Nrf2), the regulator of these
      enzyme, was translocated from the cytosol to the nucleus by 100 MUM TD. In
      summary, moderate concentrations of TD may increase the self-defence capacity of
      neuronal cells against oxidative stress.

PMID- 28503969
TI  - Essential thrombocythemia: a review of the clinical features, diagnostic
      challenges, and treatment modalities in the era of molecular discovery.
AB  - Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that is
      associated with diminished quality of life, thrombohemorrhagic complications, and
      transformation to myelofibrosis (MF) and acute leukemia (AML). The important
      recent discoveries of driver mutations, including the calreticulin gene in
      addition to JAK2 and MPL, have led to a greater understanding of disease
      pathogenesis and set the stage for the advent of more sophisticated prognostic,
      diagnostic, and therapeutic strategies. In this paper we summarize recent studies
      describing the molecular basis of ET. We review the prognostic importance of
      establishing a 'true' ET diagnosis, as well as risk factors for the development
      of adverse outcomes including thrombosis, AML (2% risk at 15 years), and MF (9%
      risk at 15 years). Finally, we discuss the decision to initiate treatment and
      assess the quality of evidence supporting the use of established, available
      therapies as well as novel treatments. Special situations, such as pregnancy,
      familial ET, and extreme thrombocytosis will also be discussed.

PMID- 28503970
TI  - Significance Test, Confidence Interval, Both or Neither?

PMID- 28503971
TI  - Mental vulnerability, Helicobacter pylori, and incidence of hospital-diagnosed
      peptic ulcer over 28 years in a population-based cohort.
AB  - OBJECTIVE: To examine whether mental vulnerability, an enduring personality
      characteristic, predicts incident hospital-diagnosed ulcer over three decades.
      MATERIALS AND METHODS: A population-based cohort study enrolled 3365 subjects
      with no ulcer history, ages 30-60, in 1982-3. Mental vulnerability, Helicobacter
      pylori IgG antibodies, socioeconomic status, and sleep duration were determined
      at baseline; non-steroidal antiinflammatory drug use, smoking, leisure time
      physical activity, and alcohol consumption both at baseline and in 1993-4.
      Hospital diagnoses of incident ulcer through 2011 were detected using the Danish
      National Patient Registry. RESULTS: Ulcers were diagnosed in 166 subjects,
      including 83 complicated by bleeding or perforation. Age-, gender-, and
      socioeconomic status-adjusted associations were significant for mental
      vulnerability (Hazard Ratio (HR) 2.0, 95% Confidence Interval 1.4-2.8),
      Helicobacter pylori (HR 1.7, CI 1.2-2.3), smoking (HR 2.0, CI 1.3-3.1), heavy
      drinking (HR 1.6, CI 1.1-2.4), abstinence (HR 1.6, CI 1.1-2.5), non-steroidal
      antiinflammatory drugs (HR 2.1, CI 1.5-3.0), and sedentary lifestyle (HR 1.9, CI
      1.4-2.7). Adjusted for all behavioral mediators, the HR for mental vulnerability
      was 1.5 (CI 1.0-2.2, p = .04). Mental vulnerability raised risk in Helicobacter
      pylori seropositive subjects and those exposed to neither Helicobacter pylori nor
      non-steroidal antiinflammatory drugs; its impact was virtually unchanged when
      analysis was limited to complicated ulcers. CONCLUSIONS: A vulnerable personality
      raises risk for hospital-diagnosed peptic ulcer, in part because of an
      association with health risk behaviors. Its impact is seen in 'idiopathic' and
      Helicobacter pylori-associated ulcers, and in acute surgical cases.

PMID- 28503972
TI  - Molecular mechanisms of anti-oxidant and anti-aging effects induced by
      convallatoxin in Caenorhabditis elegans.
AB  - Convallatoxin is widely used as a cardiac glycoside in acute and chronic
      congestive heart-failure and paroxysmal tachycardia, with many effects and
      underlying protective mechanisms on inflammation and cellular proliferation.
      However, convallatoxin has not been investigated in its antioxidant effects and
      lifespan extension in Caenorhabditis elegans. In this study, we found that
      convallatoxin (20 MUM) could significantly prolong the lifespan of wild-type C.
      elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased
      thermotolerance and resistance to paraquat-induced oxidative stress.
      Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin
      accumulation and reactive oxygen species levels in C. elegans, which were
      attributed to hormesis, free radical-scavenging effects in vivo, and up
      regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1.
      Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to
      contribute to the stress-resistance effect of convallatoxin. In summary, this
      study demonstrates that convallatoxin can protect against heat and oxidative
      stress and extend the lifespan of C. elegans, pointing it as a potential novel
      drug for retarding the aging process in humans.

PMID- 28503973
TI  - Metformin use in diabetics with diverticular disease is associated with reduced
      incidence of diverticulitis.
AB  - BACKGROUND AND AIMS: There is no current, evidence-based therapy to prevent acute
      diverticulitis in patients with diverticular disease. Metformin has been shown to
      have anti-inflammatory effects in a number of disease states, in both animal
      models and in human observational studies. The potential therapeutic efficacy of
      metformin in diverticular disease has not been investigated. This study aims to
      describe the relationship between metformin use and diverticular disease in
      patients with diabetes mellitus. METHODS: This was a retrospective case-control
      study. It compared metformin and other hypoglycaemic medication use in diabetic
      patients with uncomplicated diverticulosis to those with acute diverticulitis.
      Patients were identified using hospital International Classification of Diseases
      10 (ICD-10) data, and radiology, pathology and scanned medical record databases
      were used to confirm diagnoses and collect all information. Chi square tests were
      used to determine significance of difference in categorical variables, and Mann
      Whitney tests were used for continuous data. RESULTS: There were 174 patients
      with uncomplicated diverticulosis and 175 patients with acute diverticulitis. A
      diagnosis of acute diverticulitis was associated with a significantly lower
      incidence of metformin use, than a diagnosis of uncomplicated diverticular
      disease (44% compared to 60%, respectively, p = .002). Other oral hypoglycaemic
      drugs and insulin were not associated with a lower incidence of diverticulitis (p
      = .12 and p = .24, respectively). CONCLUSION: Metformin use is associated with
      reduced incidence of diverticulitis in diabetic patients with diverticular
      disease. The utility of metformin as a therapeutic agent to reduce the risk of
      diverticulitis in patients with diverticular disease warrants further randomised,
      prospective, interventional investigation.

PMID- 28503974
TI  - Biokinetics of engineered nano-TiO2 in rats administered by different exposure
      routes: implications for human health.

PMID- 28503975
TI  - Body image after heart transplantation compared to mechanical aortic valve
      insertion.
AB  - OBJECTIVE: Heart transplantation (HT) obviously affects body image and integrity.
      However, there are very few empirical data post-transplant. METHODS: In a cross
      sectional study, 57 HT patients were compared with 47 subjects with mechanical
      aortic valve replacement (AVR) using the Dresden-Body-Image questionnaire (DKB)
      and specific questions regarding integration of the organ/device. In addition,
      affective symptoms and quality of life (QoL) were assessed (12-Item Short-Form
      Health Survey and Hospital Anxiety and Depression Scale, HADS). RESULTS: DKB-35
      scores did not differ. HT patients scored higher than AVR on specific questions
      regarding integration of the organ/device. AVR patients showed more affective
      disturbance and lower mental QoL than HT subjects. Affective scores correlated
      negatively with body image scores. Seventeen percent of all patients showed
      psychological distress (HADS scores >8). CONCLUSIONS: HT patients integrated the
      new organ well - and even better than AVR subjects did with the device. In
      general, our data corroborate a good adaptation process, in particular in HT
      patients. Similar to other reported data, a subgroup of 15-20% of patients shows
      stronger mental distress, including body image problems. These must be identified
      and treated by professionals. Patients with AVR deserve more attention in the
      future.

PMID- 28503976
TI  - Self-extubation Laryngeal Injuries at an Academic Tertiary Care Center: A
      Retrospective Pilot Study.
AB  - OBJECTIVES: The purpose of this study is to identify laryngeal symptoms and
      injuries in self-extubated patients. METHODS: A retrospective chart review was
      conducted to identify symptoms and clinical findings associated with self
      extubation. A novel scoring system was developed and used to quantify these
      findings. Symptom score included all symptoms that patients reported after self
      extubation. Clinical score consisted of laryngeal findings visualized on
      nasopharyngeal laryngoscopy. Finally, a total self-extubation score was
      calculated as the sum of the symptom and clinical scores. Additionally, duration
      of intubation and endotracheal tube size were correlated with these scores.
      RESULTS: Sixty (n = 60) patients who self-extubated in our institution's
      intensive care unit were identified. Average calculated symptom, clinical, and
      total self-extubation scores were 0.92, 1.43, and 2.35, respectively. The most
      common symptom observed was hoarseness (62%), while the most common clinical
      finding was posterior laryngeal edema (58%). A significant positive correlation
      was found between duration of intubation and both symptom score and total self
      extubation score (r = 0.314, P = .008 and r = 0.223, P = .05, respectively).
      Symptom score predicted clinical score with a significant positive correlation
      present (r = 0.278, P = .02). CONCLUSIONS: This study demonstrates that the
      majority of self-extubated patients have laryngeal symptoms and clinical
      findings. A comprehensive, multidisciplinary evaluation is warranted for self
      extubations.

PMID- 28503978
TI  - Comparison of depression symptoms between primary depression and secondary-to
      schizophrenia depression.
AB  - OBJECTIVES: This study exclusively aimed to clinically assess which symptom
      pattern discriminates primary depression from depression-secondary to
      schizophrenia. METHODS: A total of 98 patients with primary depression and 71
      patients with secondary-to-schizophrenia depression were assessed for identifying
      the clinical phenomena of depression. Diagnosis of schizophrenia was confirmed by
      Mini International Neuropsychiatric Interview. Each participant was, however,
      assessed by Patient Health Questionnaire-9 as well as Calgary Depression Scale
      for Schizophrenia (CDSS) for possible concurrent depressive symptoms. RESULTS:
      Depressed mood, loss of interest, reduced energy and pathological guilt were more
      common in primary depression, whereas sleep disturbance and guilty ideas of
      reference were more amounting towards the diagnosis of depression secondary-to
      schizophrenia. CONCLUSIONS: It is clinically hard to differentiate primary from
      secondary-to-schizophrenia depression, especially in the absence of obvious
      psychotic symptoms. However, the classical symptoms of depression like subjective
      depressed mood, anhedonia, reduced energy and pathological guilt are more
      prominent in the primary depression.

PMID- 28503977
TI  - Emerging treatments for ulcerative colitis: a systematic review.
AB  - OBJECTIVES: Various investigational medicinal products have been developed for
      ulcerative colitis (UC). Our aim was to systematically evaluate novel
      pharmacological therapeutic agents for the treatment of UC. MATERIAL AND METHODS:
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      recommendations were followed. A search of the medical literature was conducted
      in the MEDLINE database for original research papers published between 01 January
      2010 and 31 October 2014. RESULTS: Twenty one studies, including 11,524 adults
      were analyzed. Thirteen different novel therapeutic drug options were identified.
      Vedolizumab and golimumab were superior to placebo as induction and maintenance
      therapy. Tofacitinib showed dose related efficacy for induction therapy.
      Etrolizumab showed higher clinical remission rates compared to placebo.
      Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may
      become a mesalamine alternative for mild to moderate UC. PF00547,659 was well
      tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept,
      rituximab and visilizumab did not lead to improved outcomes compared to placebo.
      Higher concentration of BMS 936557 was associated with improved efficacy compared
      to placebo. Basiliximab did not enhance corticosteroid efficacy. CONCLUSIONS:
      Patients with UC might achieve clinical response or remission by utilizing some
      of these agents with a favorable side effect profile. Further studies are needed
      to evaluate their short- and long-term efficacy and safety.

PMID- 28503979
TI  - Expression of the IFNAR1 chain of type 1 interferon receptor in benign cells
      protects against progression of acute leukemia.
AB  - Type I interferons (IFN) were widely used for leukemia treatment. These cytokines
      act on cell surface receptor consisting of the IFNAR1/2 chains to induce anti
      tumorigenic effects. Given that levels of IFNAR1 can be regulated by
      phosphorylation-driven ubiquitination and degradation that undermines IFN
      signaling and anti-tumorigenic effects, we sought to determine the importance of
      IFNAR1 downregulation in progression of acute leukemia. Using knock-in mice
      deficient in downregulation of IFNAR1, we uncovered that IFNAR1 expression in
      stromal benign cells functions to protect against progression of leukemia. We
      discuss putative mechanisms of this regulation and potential of therapeutic
      targeting of IFNAR1 downregulation to treat leukemia.

PMID- 28503980
TI  - Assessment of oxidative stress induced by gold nanorods following intra-tracheal
      instillation in rats.
AB  - Gold nanorods (GNRs) are used for their wide variety of applications in various
      industries. There is a little availability of data related to toxicity and
      ecological implications of these GNRs. The study evaluated the oxidative stress
      induction following intra-tracheal instillation of 1 and 5 mg/kg b.w. doses of 10
      and 25 nm GNRs by estimating various oxidative stress markers including lipid
      peroxidation (malondialdehyde; MDA), glutathione (GSH), superoxide dismutase
      (SOD), catalase and total antioxidant capacity (TAC) after 1 day, 1 week, 1
      month, and 3 months post exposure periods. The results have shown increased MDA
      levels and decreased GSH levels following 1 day and 1 week post exposure periods,
      indicating induction of oxidative stress. Also, the SOD, catalase and TAC levels
      were significantly decreased following exposure of both 10 and 25 nm GNRs after 1
      day and 1 week after exposures, indicating the inhibition of antioxidant defense
      mechanisms. Moreover, the 10 nm GNRs at 5 mg/kg dose displayed greater changes in
      all the estimated parameters, representing dose and size based induction of
      oxidative stress by GNRs. In contrast, a little change was observed during 1
      month and 3 months post exposure periods, may be due to recovery. Finally, the
      GNRs induced dose-size-dependent oxidative stress induction by various oxidative
      stress markers following intra-tracheal instillation in rats.

PMID- 28503981
TI  - Platelet reactivity influences clot structure as assessed by fractal analysis of
      viscoelastic properties.
AB  - Despite the interwoven nature of platelet activation and the coagulation system
      in thrombosis, few studies relate both analysis of protein and cellular parts of
      coagulation in the same population. In the present study, we use matched ex vivo
      samples to determine the influences of standard antiplatelet therapies on
      platelet function and use advanced rheological analyses to assess clot formation.
      Healthy volunteers were recruited following fully informed consent then treated
      for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10
      mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel
      (10 mg) or aspirin (75 mg) plus ticagrelor (90 mg). Blood samples were taken at
      day 0 before treatment and at day 7 following treatment. We found that aspirin
      plus prasugrel or aspirin plus ticagrelor inhibited platelet responses to
      multiple agonists and reduced P-selectin expression. Significant platelet
      inhibition was coupled with a reduction in fractal dimension corresponding to
      reductions in mean relative mass both for aspirin plus prasugrel (-35 +/- 16%
      change, p = 0.04) and for aspirin plus ticagrelor (-45 +/- 14% change, p = 0.04).
      Aspirin alone had no effect upon measures of clot structure, whereas prasugrel
      reduced fractal dimension and mean relative mass. These data demonstrate that
      platelets are important determinants of clot structure as assessed by fractal
      dimension (df) and that effective platelet inhibition is associated with a
      weaker, more permeable fibrin network. This indicates a strong association
      between the therapeutic benefits of antiplatelet therapies and their abilities to
      reduce thrombus density that may be useful in individual patients to determine
      the functional relationship between platelet reactivity, eventual clot quality,
      and clinical outcome. df could represent a novel risk stratification biomarker
      useful in individualizing antiplatelet therapies.

PMID- 28503983
TI  - Design and in vitro evaluation of tenofovir-loaded vaginal gels for the
      prevention of HIV infections.
AB  - Infection with the human immunodeficiency virus (HIV) is affecting women
      disproportionally with increasing incidence rates over the last decades.
      Tenofovir is one of the most commonly used antiretroviral agents, which belongs
      to the nucleoside/nucleotide reverse transcriptase inhibitor family, for the
      prevention of HIV acquisition. In scope of this study, a thermogelling system
      containing tenofovir-loaded chitosan nanoparticles for the controlled release of
      tenofovir was developed and characterized. The in vitro release studies have
      shown that the burst release effect was decreased to 27% with f-TFV CS NPs-Gel.
      Gelation temperature of developed formulation was found as 26.6 +/- 0.2  degrees
      C, which provides ease of administration while gelation occurs after the
      administration to the vagina. The work of adhesion values was used as parameters
      for comparison of mucoadhesive performance and the mucoadhesion of f-TFV CS NPs
      Gel was found as 0.516 +/- 0.136 N.s at 37  degrees C. The biocompatibility of
      blank formulations was evaluated by cell viability studies using L929 cells, in
      which Gel + CS NPs formulation was found to be safe with 82.4% and 90.2% cell
      viability for 1:16 and 1:32 dilutions, respectively. In conclusion, an improved
      tenofovir containing vaginal gel formulation was successfully developed and
      evaluated for preventing HIV transmission.

PMID- 28503982
TI  - Anxiety and depression affect pain drawings in cervical degenerative disc
      disease.
AB  - INTRODUCTION: Pain drawings have been frequently used in the preoperative
      evaluation of spine patients. Until now most investigations have focused on low
      back pain patients, even though pain drawings are used in neck pain patients as
      well. The aims of this study were to investigate the pain drawing and its
      association to preoperative demographics, psychological impairment, and pain
      intensity. METHODS: We carried out a post hoc analysis of a randomized controlled
      trial, comparing cervical disc replacement to fusion for radiculopathy related to
      degenerative disc disease. Preoperatively the patients completed a pain drawing,
      the Hospital Anxiety and Depression Scale (HADS), and a visual analogue scale
      (VAS). The pain drawing was evaluated according to four established methods, now
      modified for cervical conditions. Comparisons were made between the pain drawing
      and age, sex, smoking, and employment status as well as HADS and VAS. RESULTS:
      Included were 151 patients, mean age of 47 years, female/male: 78/73. Pain
      drawing results were not affected by age, sex, smoking, and employment status.
      Patients with non-neurogenic pain drawings according to the modified method by
      Ransford had higher points on HADS-anxiety, HADS-depression, and HADS-total.
      Patients with markings in the head region had higher score on HADS-depression.
      Markings in the neck and lower arm region were associated with high values of VAS
      neck and VAS-arm. CONCLUSIONS: Pain drawings were affected by both pain intensity
      and anxiety/depression in cervical spine patients. Therefore, the pain drawing
      can be a useful tool when interpreting the patients' pain in correlation to
      psychological impairment and pain location.

PMID- 28503984
TI  - The genotoxic effect of oxcarbazepine on mice blood lymphocytes.
AB  - This study was conducted to assess the amount of DNA damage caused by
      Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE)
      technique/comet assay. OXC derived from dibenzazepine series is an effective
      second generation antiepileptic drug (AED) for both children and adults. Side
      effects like genotoxic effects of AEDs are of prime importance resulting from
      toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight
      adult male Bagg's albino mice (BALB/c) were randomly classified into eight
      groups, each comprising of six animals. Two of these groups were control and six
      were tested groups. Control groups were injected with 1% tween 80 while tested
      groups were injected with 10, 20, and 40 mg/kg-day OXC for seven days (acute
      therapy) and 28 days (subchronic therapy) in peritoneal cavity. Blood samples
      were collected by cardiac puncture and subjected to comet assay for the analysis
      of DNA damage. Per sample 100 cells were scored and classified according to comet
      tail length. The results showed that OXC in acute and long term therapies had
      significantly higher (p < 0.05) genotoxicity in treated groups as compared to
      control groups. Our study suggests that OXC may cause significant DNA damage in
      both acute as well as in subchronic therapies.

PMID- 28503985
TI  - Diagnostic and Therapeutic Management of a First Unprovoked Seizure in Children
      and Adolescents With a Focus on the Revised Diagnostic Criteria for Epilepsy.
AB  - By definition, unprovoked seizures are not precipitated by an identifiable
      factor, such as fever or trauma. A thorough history and physical examination are
      essential to caring for pediatric patients with a potential first unprovoked
      seizure. Differential diagnosis, EEG, neuroimaging, laboratory tests, and
      initiation of treatment will be reviewed. Treatment is typically initiated after
      2 unprovoked seizures, or after 1 seizure in select patients with distinct
      epilepsy syndromes. Recent expansion of the definition of epilepsy by the ILAE
      allows for the diagnosis of epilepsy to be made after the first seizure if the
      clinical presentation and supporting diagnostic studies suggest a greater than
      60% chance of a second seizure. This review summarizes the current literature on
      the diagnostic and therapeutic management of first unprovoked seizure in children
      and adolescents while taking into consideration the revised diagnostic criteria
      of epilepsy.

PMID- 28503986
TI  - Minority stress model components and affective well-being in a sample of sexual
      orientation minority adults living with HIV/AIDS.
AB  - To date very little literature exists examining theoretically-based models
      applied to day-to-day positive and negative affective well-being among lesbian,
      gay, and bisexual (LGB) persons living with HIV/AIDS (PLWHA). Grounded in the
      perspective of Meyer, I. H. (2003). Prejudice, social stress, and mental health
      in lesbian, gay, and bisexual populations: Conceptual issues and research
      evidence. Psychological Bulletin, 129, 674-697. Minority Stress Model, the
      present study examined HIV- and sexual orientation-related factors influencing
      affective well-being (i.e., positive affect, negative affect, life satisfaction,
      and stress). Participants were 154 HIV-positive LGB adults from an urban area in
      the southwestern United States. Data were drawn from an archival database (i.e.,
      Project Legacy). The study methodology featured a cross-sectional self-report
      survey of minority stress, victimization, coping, and emotional well-being, among
      other subjects. Primary regression results were: (1) males reported less general
      stress than females; (2) higher internalized HIV-related stigma was associated
      with elevated negative affect; (3) higher internalized homophobia was associated
      with elevations in negative affect and general stress; (4) higher coping self
      efficacy was associated with lesser negative affect, lesser general stress,
      greater positive affect, and greater satisfaction with life; (5) a significant
      interaction between HIV-related victimization and coping self-efficacy showed
      that coping self-efficacy was positively associated with positive affect only
      (only for non-victims). Contrary to expectations, coping self-efficacy
      demonstrated the largest main effects on affective well-being. Results are
      discussed with regard to potential need for theoretical refinement of Minority
      Stress Model applied to PLWHA and affective well-being outcomes. Recommendations
      are offered for future research.

PMID- 28503987
TI  - Prevalence of chronic kidney disease and its determinants in coronary heart
      disease patients in 24 European countries: Insights from the EUROASPIRE IV survey
      of the European Society of Cardiology.
AB  - Aims Chronic kidney disease (CKD) is associated with the development and
      progression of coronary heart disease (CHD), in addition to classic
      cardiovascular risk factors. We analysed the prevalence of CKD in CHD patients
      from 24 European countries in the ambulatory setting and in a preceding hospital
      stay for CHD (index). Methods and results A total of 7998 EUROASPIRE IV
      participants (median 65 years of age, 76% male) attended a study visit 6-36
      months after the index hospitalisation. CKD was classified according to stages of
      estimated glomerular filtration rate (eGFR) and albuminuria (urinary
      albumin/creatinine ratio). In stable CHD conditions (study visit), 17.3% had CKD
      (eGFR <60 mL/min/1.73 m2) with variation among participating countries (range
      13.1-26.4%). A further 12% presented with preserved eGFR but significant
      albuminuria. During the hospital stay due to a coronary event, impaired kidney
      function was observed in 17.6% (range 7.5-38.2%). Risk factors for impaired
      kidney function included older age, female gender, classic cardiovascular (CV)
      risk factors, details of CHD history and congestive heart failure (multivariate
      regression). Of all patients, 38.9% had declined, 31.3% were stable and 29.8% had
      improved kidney function between hospital discharge and the study visit,
      dependent on age, gender, CV risk factors, CHD history and cardiac dysfunction
      (multivariate regression). Conclusions Every fifth CHD patient had CKD, while
      every tenth exhibited albuminuria as the sole indicator of kidney damage. These
      subjects are at increased risk of progression of CKD and CHD complications. After
      hospital stays due to CHD, there is potential of recovery of kidney function, but
      our findings underline the importance of identifying patients who are at high
      risk of developing CKD in order to counteract disease progression.

PMID- 28503988
TI  - The usefulness of narrow-band imaging for the diagnosis and treatment of vocal
      fold leukoplakia.
AB  - OBJECTIVE: This research was aimed to explore the efficacy of narrow-band imaging
      (NBI) on distinguishing the degree of dysplasia of vocal fold leukoplakia.
      METHODS: Patients were examined by flexible endoscopy, under white light
      endoscopy (WLE) and NBI. 78 lesions were divided into two groups according to the
      NBI classification. Group 1: non-dysplasia (ND), including squamous hyperplasia
      with hyperkeratosis or parakeratosis; Group 2: squamous hyperplasia with mild or
      moderate dysplasia (MD) or severe dysplasia (SD), or carcinoma in situ (CIS).
      RESULTS: The diagnostic accuracy of NBI for Group 1 and Group 2 was 69.70%
      (23/33) and 95.56% (43/45), respectively, and the kappa index was 0.711 and a p
      value < .05, which was considered statistically significant. CONCLUSIONS: The NBI
      could roughly estimate the degree of dysplasia. Differentiating between ND, MD,
      SD, and CIS, which may be useful for clinicians on selecting suitable therapies.

PMID- 28503989
TI  - Intravenous olfactory test latency correlates with improvement in post-infectious
      olfactory dysfunction.
AB  - CONCLUSION: This cohort study showed that onset latency in the intravenous
      olfactory test (IVO) may help predict when olfaction in patients with post
      infectious olfactory dysfunction (PIOD) improves. OBJECTIVES: To identify factors
      that predict the olfactory improvement period in patients with PIOD.
      METHODOLOGY/PRINCIPAL: All consecutive patients presenting with PIOD in 1994-2014
      who were followed up for 2 years were identified retrospectively. The ability of
      demographic/clinical factors (age, sex, body mass index, presence/absence of
      allergic rhinitis, treatment/non-treatment with herbal medicines, patient
      dependence on herbal medicine treatment, presence/absence of diabetes mellitus,
      and smoking status) and olfactory test factors (response/no response and onset
      latency and duration in the IVO test, and detection and recognition scores on the
      T&T olfactory test) to predict the olfactory improvement period (defined
      respectively as the time from PIOD onset or olfactory testing to the first self
      report of olfaction improvement) was analyzed by univariate and multivariate
      regression. RESULTS: Of the 187 PIOD patients, the prognostic ability of
      demographic/clinical factors was analyzed in 65. None predicted the olfactory
      improvement period. Of the 65 patients, 20 did not respond in the IVO test. In
      the remaining 45 patients, onset latency (but not the other olfactory test
      factors) was a significant prognosticator of olfactory improvement period
      (R2=0.24, p = 0.003).

PMID- 28503990
TI  - Assessing the utilization of radiotherapy near end of life at a Finnish
      University Hospital: a retrospective cohort study.
AB  - BACKGROUND: Palliative radiotherapy can improve quality of life for cancer
      patients during the last months of life. However, very short life expectancy may
      devastate the benefit of the treatment. This single center study assesses the
      utilization of radiotherapy during the last weeks of life. MATERIAL AND METHODS:
      All cancer patients (N = 38,982) treated with radiotherapy (N = 11,395) in Turku
      University Central Hospital during 2005-2013 were identified in the database
      consisting of electronic patient records. One fourth (N = 2904, 25.5%) of the
      radiotherapy treatments were given during the last year of life. The last
      radiotherapy treatments and the time from the last radiotherapy treatment to
      death were assessed in regards to patients' age, cancer diagnosis, domicile,
      place of death and the treatment year. Treatments given during the last two weeks
      of life were also assessed regarding the goal of treatment and the reason for
      possible discontinuation. RESULTS: The median time from the last fraction of
      radiotherapy to death was 84 d. During the last two weeks before death (N = 340),
      pain (29.4%) was the most common indication for radiotherapy. Treatment was
      discontinued in 40.6% of the patients during the last two weeks of life, and
      worsening of general condition was the most common reason for discontinuity
      (70.3%). The patients receiving radiotherapy during the last weeks of life were
      more likely to die in tertiary care unit. During the last year of life single
      fraction treatment was used only in 7% of all therapy courses. There was a
      statistically significant (p < .05) decrease in the median number of fractions in
      the last radiotherapy treatment between 2005-2007 (8 fractions) and 2011-2013 (6
      fractions). CONCLUSIONS: Up to 70% of the treatments during the last two weeks of
      life were not delivered to alleviate pain and utilization of single fraction
      radiotherapy during the last year of life was infrequent. These observations
      suggest that practice of radiotherapy during the last weeks of life should be
      revisited.

PMID- 28503991
TI  - Platelet concentrates modulate myeloid dendritic cell immune responses.
AB  - Platelet transfusion has been reported to modulate the recipients' immune system.
      To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased
      rate of mortality, morbidity, infectious complications and prolonged hospital
      stays) following platelet transfusion are largely undefined. To determine the
      potential for platelet concentrates (PC) to modulate responses of crucial immune
      regulatory cells, a human in vitro whole blood model of transfusion was
      established. Maturation and activation of human myeloid dendritic cells (mDC) and
      the specialized subset blood DC antigen (BDCA)3+ DC were assessed following
      exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry). In
      parallel, to model recipients with underlying viral or bacterial infection,
      polyinosinic:polycytidylic acid or lipopolysaccharide was added. Exposure to PC
      had less of an impact on mDC responses than BDCA3+ DC responses. PC alone
      downregulated BDCA3+ DC expression of co-stimulatory molecules CD40 and CD80. In
      the model of viral infection, PC downregulated expression of CD83, and in the
      bacterial model of infection, PC downregulated CD80, CD83, and CD86. PC alone
      suppressed mDC production of interleukin (IL)-8, IL-12 and tumor necrosis factor
      (TNF)-alpha and BDCA3+ DC production of IL-8, IL-12, and IL-6. In the model of
      viral infection, production of IL-12 and interferon-gamma inducible protein (IP)
      10 was reduced in both DC subsets, and IL-8 was reduced in BDCA3+ DC following PC
      exposure. When modeling bacterial infection, PC suppressed mDC and BDCA3+ DC
      production of IL-6 and IL-10 with a reduction in TNF-alpha evident in mDC. This
      study assessed the impact of PC "transfusion" on DC surface antigen expression
      and inflammatory mediator production and provided the first evidence that PC
      transfusion modulates blood mDC and BDCA3+ DC maturation and activation,
      particularly in the models of infection. Results of this study suggest that
      patients who receive PC, particularly those with underlying infectious
      complications, may fail to establish an appropriate immune response precipitating
      poor patient outcomes.

PMID- 28503992
TI  - Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in
      mouse cochlea.
AB  - OBJECTIVE: This study aimed in fully investigating the toxicities of ouabain to
      mouse cochlea and the related cellular environment, and providing an optimal
      animal model system for cell transplantation in the treatment of auditory
      neuropathy (AN) and sensorineural hearing loss (SNHL). METHODS: Different dosages
      of ouabain were applied to mouse round window. The auditory brainstem responses
      and distortion product otoacoustic emissions were used to evaluate the cochlear
      function. The immunohistochemical staining and cochlea surface preparation were
      performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair
      cells. RESULTS: Ouabain at the dosages of 0.5 mM, 1 mM and 3 mM selectively and
      permanently destroyed SGNs and their functions, while leaving the hair cells
      relatively intact. Ouabain at 3 mM resulted in the most severe SGNs loss and
      induced significant loss of Schwann cells started as early as 7 days and with
      further damages at 14 and 30 days after ouabain exposure. CONCLUSIONS: The
      application of ouabain to mouse round window induces damages of SGNs and Schwann
      cells in a dose- and time-dependent manner, this study established a reliable and
      accurate animal model system of AN and SNHL.

PMID- 28503993
TI  - Dual inhibition of PI3K and mTOR by VS-5584 suppresses thrombus formation.
AB  - VS-5584 is a highly selective dual kinase inhibitor which suppresses
      phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR)
      activity. Because these kinases are crucially involved in primary hemostasis, we
      herein investigated the effect of this compound on thrombus formation in vitro
      and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP)
      with VS-5584 inhibited the agonist-induced activation of surface glycoprotein
      complex (GP)IIb/IIIa and the upregulation of P-selectin. This was associated with
      a significantly reduced formation of platelet-leukocyte aggregates (PLA). VS-5584
      further attenuated platelet aggregation and adhesion after agonist stimulation.
      In contrast, endothelial expression of intercellular adhesion molecule (ICAM)-1
      and vascular cellular adhesion molecule (VCAM)-1 and secretion of von Willebrand
      Factor (vWF) were not affected by the dual kinase inhibitor. In vivo, VS-5584
      inhibited photochemically induced thrombus formation as shown by a significantly
      prolonged time to complete vessel occlusion when compared to vehicle-treated
      controls. This was associated with an elevated tail vein bleeding time,
      indicating a potential hemorrhagic risk in VS-5584-treated mice. Taken together,
      these novel findings demonstrate that VS-5584 is a potent inhibitor of primary
      hemostasis targeting multiple platelet functions.

PMID- 28503994
TI  - Anti-pseudomonal and anti-endotoxic effects of surfactin-stabilized biogenic
      silver nanocubes ameliorated wound repair in streptozotocin-induced diabetic
      mice.
AB  - Pseudomonas aeruginosa and its lipopolysaccharides play a key role in the
      pathogenesis of diabetic foot infection, for which, currently no effective
      therapeutic agents are available. Hence, newer forms of therapeutic agents are
      required for treating Pseudomonas aeruginosa infection. In this present study,
      nanocrystalline silver nanoparticles (AgNPs) were synthesized using culture
      filtrate of Brevibacillus brevis KN8(2) followed by an investigation of its in
      vivo anti-pseudomonal and anti-endotoxic properties. Biosynthesized AgNPs was
      predominantly cubical in shape with an average particle size of 15.40 nm as
      observed through field emission scanning electron microscopy (FESEM) and X-ray
      diffraction analysis. The LC-ESI-MS/MS analysis indicates the presence of
      surfactin in culture filtrate of B. brevis KN8(2). The MIC of surfactin
      stabilized AgNPs against P. aeruginosa was 10 MUg ml-1 and its wound repair
      activity was observed in P. aeruginosa-infected wounds of diabetic mice by
      measuring wound area closure, bacterial counts, mRNA expressions, and
      histopathology. Further, surfactin-stabilized AgNPs suppressed the transcription
      of LPS-triggered expression of the TNF-alpha in wounds that LPS-assisted
      extension of wound repair in diabetes mellitus conditions was circumvented quite
      well. Results gathered in this study established that surfactin-stabilized AgNPs
      could effectively offer to the novel treatment of Gram-negative bacilli infection
      in diabetic wounds.

PMID- 28503995
TI  - Preparation and characterization of surface-modified PLGA-polymeric nanoparticles
      used to target treatment of intestinal cancer.
AB  - Docetaxel (DTX), a cytotoxic taxane, is a poor water-soluble drug and exhibits
      less oral bioavailability. Current research investigates the effective transport,
      for DTX-loaded chitosan (CS)-coated-poly-lactide-co-glycolide (PLGA)
      nanoparticles (NPs) (DTX-CS-PLGA-NPs) and DTX-PLGA-NPs as well as a novel third
      generation P-gp inhibitor i.e. GF120918 (Elacridar), across intestinal epithelium
      with its successive uptake by the tumour cells in an in vitro model. The prepared
      NPs showed a spherical shape particle size i.e. <123.96 nm with polydispersity
      index (PDI) of <0.290 whereas for CS-coated NPs, the zeta potential was converted
      from negative to positive value along with a small modification in particle size
      distribution. The entrapment efficiency observed for DTX-CS-PLGA-NPs was 74.77%,
      whereas the in vitro release profile revealed an initial rapid DTX release
      followed by a sustained release pattern. For apparent permeability, DTX-CS-PLGA
      NPs and DTX-PLGA-NPs along with GF120918 showed a five-fold (p < .01) and 2.2
      fold enhancement, respectively, as observed in rat ileum permeation study.
      Similarly, for pharmacokinetic (PK) studies, higher oral bioavailability was
      observed from DTX-CS-PLGA-NPs (5.11-folds) and DTX-PLGA-NPs (3.29-folds) as
      compared with DTX-suspension (DTX-S). Cell uptake studies on A549 cells as
      performed for DTX-CS-PLGA-NPs and DTX-PLGA-NPs loaded with rhodamine 123 dye,
      exhibited enhanced uptake as compared with plain dye solution. The enhanced
      uptake for DTX-CS-PLGA-NPs and DTX-PLGA-NPs formulations in the presence of
      GF120918 was confirmed further with the help of confocal laser scanning
      microscopic images (CLSM). The potential of the third-generation novel P-gp
      inhibitor (GF120918) investigated for the effective delivery of DTX as well as
      investigation of permeability and uptake studies whereby a strong potential of
      GF120918 for effective oral delivery was established.

PMID- 28503996
TI  - Primary Immunization of Human Papillomavirus Vaccine in the Pediatric Population:
      What Is the Verdict Now?
AB  - The safety and efficacy of a 2-dose series for the human papillomavirus vaccines
      rather than a 3-dose series in older children has not been well defined. This
      article reviews the literature summarizing the use of all 3 HPV vaccines (2vHPV,
      4vHPV, 9vHPV) as a 2-dose series for females and 4vHPV and 9vHPV for males
      younger than 15 years. Six prospective trials evaluating immunogenicity of a 2
      dose series of 2vHPV and/or 4vHPV, as well as an ongoing prospective clinical
      trial for 9vHPV, are discussed. The 2-dose series with Gardasil 9(r) in both
      males and females ages 9 to 14 years appears to be the most widely accepted
      recommendation. The exact time schedule between the 2 vaccines varies among
      studies, but it seems that they should be separated by 6 to 12 months. Federal
      and world-wide organizations' (ie, Centers for Disease Control and Prevention,
      Food and Drug Administration, and World Health Organization) opinions and
      recommendations on the appropriate scheduling of the vaccines are also
      highlighted.

PMID- 28503997
TI  - Television During Meals in the First 4 Years of Life.
AB  - The development of children's mealtime television (TV) habits has not been well
      studied. We assessed whether mealtime TV habits established in infancy will
      persist into early childhood. We analyzed data collected through parent surveys
      at birth and at 6-month intervals from a randomized controlled trial. We used t
      tests, chi2 tests, and a multivariable logistic regression to determine if family
      characteristics were associated with mealtime TV. A McNemar test was used to
      assess whether mealtime TV exposure changed over time. College-educated fathers
      and families with an annual income >$50 000 were associated with less-frequent TV
      exposure during children's mealtimes. It was found that 84% of children retained
      their level of exposure to TV during mealtimes from the first 24 months through
      48 months of life. Clinicians should counsel families about mealtime TV use
      within the first 2 years of life because these habits seem to develop early and
      persist into at least early childhood.

PMID- 28503998
TI  - Reducing Errors in an Emergency Center Setting Using an Automated Fluorescence
      Immunoassay for Group A Streptococcus Identification.

PMID- 28504000
TI  - Factors associated with successful decannulation in pediatric tracheostomy
      patients.
AB  - OBJECTIVES: To investigate the outcome of pediatric tracheostomy and identify
      predictive factors for successful decannulation. METHODS: We performed a
      retrospective chart review of a series of 42 consecutive patients of less than 24
      months of age who underwent a tracheostomy between 2012 and 2015. RESULTS:
      Successful decannulation was achieved in 11 patients (26%). Thirty-one patients
      (74%) remained tracheostomy-dependent. Of the 11 patients who were successfully
      decannulated, 10 (91%) had only structural disorders and nine (82%) were able to
      walk unassisted; importantly, nine (82%) were able to swallow following
      decannulation. In contrast, of the 31 patients who did not tolerate
      decannulation, 21 (68%) had functional disorders and 18 (58%) were unable to walk
      unassisted; 20 (65%) of the tracheostomy-dependent patients were unable to
      swallow after undergoing surgery. CONCLUSION: Following pediatric tracheostomy
      procedures, patients with solely structural disorders were significantly more
      likely to be successfully decannulated compared to patients with functional
      disorders. Furthermore, the capacity to walk unassisted and swallow after surgery
      is associated with positive outcomes for decannulation. Our results suggest that
      an objective evaluation of the ability to walk unassisted, and to ingest food,
      may be useful for predicting the outcome and effects of tracheostomy procedures
      and decannulation in children.

PMID- 28503999
TI  - Quantitative assessment of brain glucose metabolic rates using in vivo deuterium
      magnetic resonance spectroscopy.
AB  - Quantitative assessment of cerebral glucose consumption rate (CMRglc) and
      tricarboxylic acid cycle flux (VTCA) is crucial for understanding neuroenergetics
      under physiopathological conditions. In this study, we report a novel in vivo
      Deuterium (2H) MRS (DMRS) approach for simultaneously measuring and quantifying
      CMRglc and VTCA in rat brains at 16.4 Tesla. Following a brief infusion of
      deuterated glucose, dynamic changes of isotope-labeled glucose,
      glutamate/glutamine (Glx) and water contents in the brain can be robustly
      monitored from their well-resolved 2H resonances. Dynamic DMRS glucose and Glx
      data were employed to determine CMRglc and VTCA concurrently. To test the
      sensitivity of this method in response to altered glucose metabolism, two brain
      conditions with different anesthetics were investigated. Increased CMRglc (0.46
      vs. 0.28 umol/g/min) and VTCA (0.96 vs. 0.6 umol/g/min) were found in rats under
      morphine as compared to deeper anesthesia using 2% isoflurane. This study
      demonstrates the feasibility and new utility of the in vivo DMRS approach to
      assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an
      alternative MRS tool for in vivo study of metabolic coupling relationship between
      aerobic and anaerobic glucose metabolisms in brain under physiopathological
      states.

PMID- 28504001
TI  - N-acetylcysteine potentiates diclofenac toxicity in Saccharomyces cerevisiae:
      stronger potentiation in ABC transporter mutant strains.
AB  - Diclofenac (DCF) adverse reactions involve diverse mechanisms in different
      models. We recently demonstrated that DCF-induced toxicity in HepaRG decreases as
      they express DCF-metabolizing enzymes. DCF metabolism promotes toxicity in
      Saccharomyces cerevisiae expressing heterologous cytochromes-P450. N
      Acetylcysteine (NAC) is used to treat diverse medical conditions due to its
      multiple properties (antioxidant, metal chelator, thiol-disulfide disruption).
      The latter property accounts for its mucolytic effects and broadens its potential
      molecular targets to signal transduction proteins, ABC transporters and others.
      Interaction of NAC with DCF effects depends on the experimental model. This study
      aims to investigate NAC/DCF interaction and the involvement of ABC transporters
      in wild type and mutant Saccharomyces cerevisiae. DCF inhibited yeast growth in a
      dose- and time-dependent manner and the cells started adapting to DCF 24-h post
      treatment. NAC potentiated DCF-induced toxicity if added prior or parallel to
      DCF. Pretreatment with NAC increased its potentiation effect and compromised
      cells adaption to DCF. Post-treatment with NAC potentiated DCF toxicity without
      compromising adaptation. Moreover, mutant strains in ABC transporters Pdr5, Yor1,
      Bpt1 or Pdr15, were more sensitive to DCF; while mutant strains in Pdr5, Vmr1 or
      Pdr12 were more sensitive to NAC/DCF interaction. DCF +/- NAC elicited on the
      mutant strain in Yap1, an oxidative stress-related protein, the same effects as
      on the wild type. Therefore, oxidative stress does not seem to be key actor in
      DCF toxicity in our model. Our hypothesis is that NAC potentiation effect is at
      least due to its ability to disrupt disulfide bridge in proteins required to
      overcome DCF toxicity in yeast.

PMID- 28504002
TI  - Development and evaluation of a novel score for prediction of large oesophageal
      varices in patients with hepatitis c virus-induced liver cirrhosis.
AB  - OBJECTIVE: Variceal bleeding is one of the most common life-threatening
      complications of liver cirrhosis. This study aimed to develop and evaluate a
      predictive score, named Platelet count, Alpha fetoprotein (AFP) and Prothrombin
      INR (PAP) for the prediction of large oesophageal varices and to compare PAP
      score with eight common liver fibrosis scores (AAR, APRI, GUCI, BRC score, Fibro
      Alfa, FIB4, Lok and Fibro-Q) in patients with hepatitis C virus (HCV) induced
      liver cirrhosis. METHODS: A total of 277 patients with HCV-induced liver
      cirrhosis were evaluated by upper gastrointestinal endoscopy for presence of
      varices. Liver biochemical profile, complete blood count, prothrombin time and
      AFP were estimated. Stepwise linear discriminant analysis and area under receiver
      operating characteristic curves (AUCs) were used to create a predictive score
      (PAP score) comprising platelet count, AFP and prothrombin-INR. RESULTS: PAP
      score predicts large oesophageal varices in patients with HCV-induced liver
      cirrhosis with AUC of 0.85. The optimum cut-off for predicting large oesophageal
      varices using ROC curve analysis was 0.27. At this point the PAP score had 77%
      sensitivity, 86% specificity, 94% negative predictive value and 84% efficiency.
      The diagnostic performances (AUC) of eight common liver fibrosis scores were 0.58
      for the AAR score, 0.63 for APRI, 0.66 for GUCI, 0.68 for BRC, 0.72 for Fibro
      Alfa, 0.70 for FIB4, 0.72 for Lok and 0.77 for Fibro-Q. CONCLUSION: PAP scores a
      non-invasive, inexpensive and simple score that could predict the presence of
      large oesophageal varices reducing the need of endoscopy. The PAP score has a
      superior AUC score than other scores, suggesting improved clinical value.

PMID- 28504004
TI  - Experimental and computational studies on the binding of diazinon to human serum
      albumin.
AB  - In the present research, the binding properties of diazinon (DZN), as an
      organophosphorus herbicide, to human serum albumin (HSA) were investigated using
      combination of spectroscopic, electrochemistry, and molecular modeling
      techniques. Changes in the UV-Vis and FT-IR spectra were observed upon ligand
      binding along with a significant degree of tryptophan fluorescence quenching on
      complex formation. The obtained results from spectroscopic and electrochemistry
      experiments along with the computational studies suggest that DZN binds to
      residues located in subdomains IIA of HSA with binding constant about 1410.9 M-1
      at 300 K. From the thermodynamic parameters calculated according to the van't
      Hoff equation, the enthalpy change DeltaH degrees  and entropy change DeltaS
      degrees  were found to be -16.695 and 0.116 KJ/mol K, respectively. The primary
      binding pattern is determined by hydrophobic interaction and hydrogen binding
      occurring in so-called site I of HSA. DZN could slightly alter the secondary
      structure of HSA. All of experimental results are supported by computational
      techniques such as docking and molecular dynamics simulation using a HSA crystal
      model.

PMID- 28504005
TI  - How do health behaviour interventions take account of social context? A
      literature trend and co-citation analysis.
AB  - In recent years, health behaviour interventions have received a great deal of
      attention in both research and policy as a means of encouraging people to lead
      healthier lives. The emphasis of such interventions has varied over time, in
      terms of level of intervention (e.g. individual vs community) and drawing on
      different disciplinary perspectives. Recently, a number of critiques have focused
      on how health behaviour interventions sometimes sideline issues of social
      context, framing health as a matter of individual choice and, by implication, a
      personal responsibility. Part of this criticism is that health behaviour
      interventions often do not draw on alternative social science understandings of
      the structured and contextual aspects of behaviour and health. Yet to our
      knowledge, no study has attempted to empirically assess the extent to which, and
      in what ways, the health behaviour intervention field has paid attention to
      social context. In this article, we undertake this task using bibliometric
      techniques in order to map out the health behaviour intervention field. We find
      that the number of health behaviour interventions has grown rapidly in recent
      years, especially since around 2006, and that references to social science
      disciplines and concepts that foreground issues of social context are rare and,
      relatively speaking, constitute less of the field post 2006. More quantifiable
      concepts are used most, and those more close to the complexities of social
      context are mentioned least. The document co-citation analysis suggests that pre
      2006, documents referring to social context were relatively diffuse in the
      network of key citations, but post 2006 this influence had largely diminished.
      The journal co-citation analysis shows less disciplinary overlap post 2006. At
      present, health behaviour interventions are continuing to focus on individualised
      approaches drawn from behavioural psychology and behavioural economics. Our
      findings lend empirical support to a number of recent papers that suggest more
      interdisciplinary collaboration is needed to advance the field.

PMID- 28504003
TI  - Different metabolic responses induced by long-term interdisciplinary therapy in
      obese adolescents related to ACE I/D polymorphism.
AB  - INTRODUCTION: The main purpose of the present study was to investigate whether
      I/D polymorphism of the ACE gene might affect metabolic changes related to the
      metabolic syndrome through a long-term interdisciplinary therapy in obese
      adolescents. METHODS: In total, 125 obese adolescents who entered the
      interdisciplinary obesity programme were assigned to the following two subgroups:
      metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and
      after 1 year. Genomic DNA was extracted from circulating leukocytes. RESULTS:
      Subjects with the II genotype in the non-metabolic syndrome group were only to
      increase their fat-free mass after therapy. Regarding lipid profile, subjects
      with ID and DD genotypes from both groups reduced their low-density lipoprotein
      cholesterol levels significantly. The metabolic parameters from the ID and DD
      genotypes of the non-metabolic syndrome group showed a significantly improved
      insulin response. CONCLUSION: In the present study, we showed that the ACE
      polymorphism was able to influence the fat-free mass in the I-carry allele in the
      non-metabolic syndrome group positively. In addition, the I-carry allele was able
      to improve the insulin resistance of the metabolic syndrome group significantly.
      These results suggest that the ACE I/D genotypes can influence, in different
      ways, the specific parameters of metabolism among obese adolescents submitted for
      long-term interdisciplinary therapy.

PMID- 28504006
TI  - A comparative study on the Mn/TiO2-M(M = Sn, Zr or Al) Ox catalysts for NH3-SCR
      reaction at low temperature.
AB  - A series of TiO2-M(M = Sn, Zr or Al) Ox were prepared and manganese oxide (MnOx)
      was supported on the carrier by the traditional impregnation method for low
      temperature selective catalytic reduction (SCR) of NOx with ammonia as a
      reductant. The obtained catalysts were characterized by XRD, BET, high-resolution
      transmission electron microscope (HRTEM), H2-TPR, NH3-TPD, X-ray photoelectron
      spectroscopy (XPS) and in situ Fourier-transform infrared (FT-IR) and their
      catalytic activities for NOx reduction with NH3 in the presence of SO2 were
      investigated comparatively. The results showed that the highest NOx conversion of
      over 90% could be obtained with the Mn/Ti-Sn catalyst at a wide range of
      temperature window of 150-270 degrees C. The combination of characterization
      techniques, such as BET, XRD and HRTEM, revealed that manganese oxides were well
      dispersed on Ti-Sn. H2-TPR suggested that Ti-Sn and Ti-Zr supports could enhance
      the reduction ability of catalysts. Accordingly, Mn/Ti-Al exhibited worse
      activity at low temperature. XPS results were in good agreement with H2-TPR
      results, and Mn/Ti-Sn had more surface-reducible species of Mn4+ ions and more
      surface-adsorbed oxygen species, which was conducive to SCR reaction. The in situ
      FT-IR spectra of NH3 adsorption indicated that all the modified catalysts had
      more Lewis acid sites and the amide species at 1506 cm-1 had a certain influence
      on the catalytic reaction at low temperature. Mn/Ti-Zr showed a stronger
      resistance to SO2 but Mn/Ti-Al was affected more adversely and all the catalysts
      could not be restored to the initial catalytic activity after stopping feeding
      SO2. NH3-TPD revealed that the total acid amount of the Mn/Ti-Sn sample was
      larger than other samples, which indicated that the Ti-Sn solid solution could
      provide more surface acid sites over the catalyst.

PMID- 28504007
TI  - Can we afford not to prevent MS-related disability?

PMID- 28504008
TI  - Maternal resolution of preterm birth from 1 to 18 months.
AB  - Preterm birth can be traumatic for some mothers, involving feelings of grief over
      the hoped-for full-term pregnancy. In this longitudinal study, we interviewed 50
      mothers of preterm infants, using the reaction to diagnosis interview when their
      child was 1 month and 18 months old. We examined change and stability in
      resolution status over time. Additionally, we explored possible predictors of
      resolution trajectories between 1 and 18 months. Findings indicated that
      resolution at 1 month was not yet common. The rate of resolution at 18 months was
      62.6%, compared with 38.2% at 1 month. Prenatal precursors of preterm birth,
      lower medical neonatal risk, and lower maternal stress at 1 month significantly
      differentiated mothers who attained resolution as early as at 1 month from those
      who were unresolved at 1 and 18 months. Lower maternal stress at 1 month was the
      only predictor that significantly differentiated initially unresolved mothers who
      later attained resolution from those who remained unresolved at 18 months.
      Discussion focuses on maternal stress, which may mark a subgroup of mothers of
      preterm infants who are at risk of being unresolved through the first 18 months,
      and who may benefit from resolution-focused intervention.

PMID- 28504009
TI  - The redox couple avarol/avarone in the fight with malignant gliomas: the case
      study of U-251 MG cells.
AB  - This study aimed to screen in vitro antitumour activity of the redox couple
      avarol/avarone against the human malignant glioma cell line U-251 MG for the
      first time. Compared both with avarol and positive controls used (temozolomide
      and doxorubicin), avarone was found to be the most active compound with IC50
      value below 1 MUM (IC50 0.68 +/- 0.04 MUM, 96 h). Considerable less DNA damage in
      the cells treated with avarol and avarone vs. doxorubicin (105 & 123% vs. 299%,
      respectively; untreated U-251 MG cells were used as a control, 100%), coupled
      with no sign of cytotoxicity against the normal human foetal lung fibroblast MRC
      5 cells (IC50 > 100 MUM), has actually pointed out the importance of this marine
      sesquiterpenoid quinone structure as a promising lead compound in development of
      novel brain chemotherapeutics.

PMID- 28504010
TI  - Effects of selective serotonin reuptake inhibitors on intraocular pressure and
      anterior segment parameters in open angle eyes.
AB  - PURPOSE: To evaluate the short- and long-term effects of selective serotonin
      reuptake inhibitors (SSRIs) on intraocular pressure (IOP) and anterior segment
      parameters in open angle eyes. MATERIALS AND METHODS: This cross-sectional study
      included 325 eyes of 166 subjects. Subjects were divided into three groups: Group
      1 included 116 eyes of 58 patients receiving SSRIs for 1 week-6 months, Group 2
      included 102 eyes of 53 patients receiving SSRIs for longer than 6 months and
      Group 3 included 107 eyes of 55 healthy subjects not receiving any drugs. All of
      the patients receiving SSRIs were diagnosed as major depressive disorder. All
      groups were chosen to be similar in terms of age and gender. All patients
      underwent a detailed ophthalmologic examination including IOP measurement by
      Goldmann applanation tonometer and gonioscopy. Anterior segment parameters
      including pupil diameter (PD), central corneal thickness (CCT), anterior chamber
      depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were
      assessed by a Scheimpflug system. RESULTS: Pupil diameter was significantly
      larger in patients receiving SSRIs for <6 months and >=6 months than the control
      subjects (3.53 +/- 0.71 mm, 3.48 +/- 0.60 mm versus 3.11 +/- 0.72 mm, p < 0.05)
      but this effect was independent from the duration of SSRI treatment. IOP was
      significantly lower in patients receiving SSRIs for <6 months and >=6 months than
      the control group (16.04 +/- 2.17 mm Hg, 16.11 +/- 2.13 mm Hg versus 17.34 +/-
      2.15 mmHg, p < 0.05), but there were no statistically significant differences
      between the patients receiving SSRIs for <6 months and >=6 months. There were no
      statistically significant differences between the patient and the control group
      in values of CCT, ACD, ACV and ACA. The ACAs were measured between 25 degrees 
      and 55 degrees  with Scheimpflug system and also classified as grade 3-4 (Shaffer
      system) by gonioscopy. CONCLUSIONS: Selective serotonin reuptake inhibitors cause
      mydriasis which is persistent during the treatment. In depression patients with
      open angle eyes, short- and long-term use of SSRIs leads to decrease in IOP.

PMID- 28504011
TI  - The future of oncology therapeutics.

PMID- 28504012
TI  - Inpatient glycemic management in internal medicine: an observational multicenter
      study in Nanjing, China.
AB  - AIMS: To evaluate the prevalence of hyperglycemia among inpatients in internal
      medicine, and specifically, to assess the glycemic management of inpatients in
      non-endocrinology departments in three large urban hospitals in China. METHODS: A
      multicenter observational study was conducted using electronic health records,
      and a survey of 1939 patients who were admitted to internal medicine units and
      followed until discharge. Those with previously diagnosed diabetes, newly
      diagnosed diabetes, or impaired fasting glucose were included. Aspects of
      glycemic management examined were (a) hyperglycemia, (b) endocrinology
      consultation for hyperglycemia and (c) hypoglycemia. RESULTS: The prevalence of
      hyperglycemia in internal medicine was 45.7% (886 out of 1939). A total of 741
      (83.6%) patients were treated by non-endocrinology departments; of those, 230
      (31.1%) were in poor glycemic control and needed an endocrinology consultation.
      Yet only 57 (24.8%) received one. In 4 cases, the physician did not follow the
      consultants' advice. Among the remaining 53 consulted patients, 35 (66.1%) were
      still in poor glycemic control, yet only about half received a second
      consultation. Finally, among patients treated in non-endocrinology departments,
      58 (7.8%) had hypoglycemia; less than half retested their blood glucose after
      treatment. CONCLUSIONS: The majority of patients with hyperglycemia were in non
      endocrinology departments. Their glycemic management was poor; the endocrinology
      consultation rate was low and the result was suboptimal. Also, the management of
      hypoglycemia was not ideal. Therefore, improving glycemic management is urgently
      needed in Chinese hospitals.

PMID- 28504013
TI  - Anti-influenza effect of the major flavonoids from Salvia plebeia R.Br. via
      inhibition of influenza H1N1 virus neuraminidase.
AB  - To determine the compounds responsible for its anti-influenza activities, we
      isolated the three flavonoids, 6-hydroxyluteolin 7-O-beta-d-glucoside (1),
      nepitrin (2), homoplantaginin (3) from the MeOH extract of Salvia plebeia R.Br.
      and identified them by comparing the spectroscopic data with that reported in the
      literature. The contents of the three flavonoids in the whole extract were 108.74
      +/- 0.95, 46.26 +/- 2.19, and 69.35 +/- 1.22 mg/g for 6-hydroxyluteolin 7-O-beta
      d-glucoside, nepitrin, and homoplantaginin, respectively, which demonstrates that
      they are the major constituents of this plant. The three flavonoids were
      evaluated for their inhibitory activities against influenza virus H1N1 A/PR/9/34
      neuraminidase and H1N1-induced cytopathic effect (CPE) on Madin-Darby canine
      kidney (MDCK) cells. Our results demonstrated the following arrangement for their
      anti-influenza activities: nepitrin (2) > 6-hydroxyluteolin 7-O-beta-d-glucoside
      (1) > homoplantaginin (3). The potent inhibitory activities of these flavonoids
      against influenza suggested their potential to be developed as novel anti
      influenza drugs in the future.

PMID- 28504014
TI  - The development of a patient-specific method for physiotherapy goal setting: a
      user-centered design.
AB  - PURPOSE: To deliver client-centered care, physiotherapists need to identify the
      patients' individual treatment goals. However, practical tools for involving
      patients in goal setting are lacking. The purpose of this study was to improve
      the frequently used Patient-Specific Complaints instrument in Dutch
      physiotherapy, and to develop it into a feasible method to improve physiotherapy
      goal setting. METHODS: An iterative user-centered design was conducted in co
      creation with the physiotherapists and patients, in three phases. Their needs and
      preferences were identified by means of group meetings and questionnaires. The
      new method was tested in several field tests in physiotherapy practices. RESULTS:
      Four main objectives for improvement were formulated: clear instructions for the
      administration procedure, targeted use across the physiotherapy process, client
      activating communication skills, and a client-centered attitude of the
      physiotherapist. A theoretical goal-setting framework and elements of shared
      decision making were integrated into the new-called, Patient-Specific Goal
      setting method, together with a practical training course. CONCLUSIONS: The user
      centered approach resulted in a goal-setting method that is fully integrated in
      the physiotherapy process. The new goal-setting method contributes to a more
      structured approach to goal setting and enables patient participation and goal
      oriented physiotherapy. Before large-scale implementation, its feasibility in
      physiotherapy practice needs to be investigated. Implications for rehabilitation
      Involving patients and physiotherapists in the development and testing of a goal
      setting method, increases the likelihood of its feasibility in practice. The
      integration of a goal-setting method into the physiotherapy process offers the
      opportunity to focus more fully on the patient's goals. Patients should be
      informed about the aim of every step of the goal-setting process in order to
      increase their awareness and involvement. Training physiotherapists to use a
      patient-specific method for goal setting is crucial for a correct application.

PMID- 28504015
TI  - Laparoscopic Surgery in Patients on Peritoneal Dialysis: A Review of the
      Literature.
AB  - Peritoneal dialysis (PD) is an effective renal replacement therapy for the
      treatment of end-stage renal disease. Patients on PD undergoing abdominal open
      surgery often fail to resume PD. Laparoscopic surgery has recently become a
      serious alternative to open surgery in patients on PD to treat different
      abdominal pathologies. However, only a few studies have reported successful
      procedures without Tenckhoff catheter removal. The aim of this review is to
      describe how a laparoscopic technique can allow PD patients to deal with
      abdominal surgery without shifting to hemodialysis. Only 50 cases of laparoscopic
      surgical intervention in PD patients have been published to our knowledge. These
      case series largely concern laparoscopic cholecystectomies, appendectomies,
      nephrectomies, colectomies, and bariatric procedures. The reported cases show how
      laparoscopic surgery can be accepted as a valid option for several abdominal
      surgical procedures in patients on PD with good outcomes and early resumption of
      PD.

PMID- 28504016
TI  - DNA isolation by galactoacrylate-based nano-poly(HEMA-co-Gal-OPA) nanopolymers.
AB  - Isolation of DNA is one of the important processes for biotechnological
      applications such as investigation of DNA structures and functions, recombinant
      DNA preparations, identification of genetic factors and diagnosis and treatment
      of genetic disorders. The aim of this study was to synthesis and characterizes
      the galactoacrylate based nanopolymers with high surface area and to investigate
      the usability of these synthesized nanopolymers for DNA isolation studies.
      Nanopolymers were synthesized by the surfactant free emulsion polymerization
      technique by using the monomers of 2-hydroxyl ethylmethacrylate and 6-O-(2'
      hydroxy-3'-acryloyloxypropyl)-1,2:3,4-di-O-isopropylidene-alpha-D
      galactopyranose. Galactoacrylate origin of these newly synthesized nanopolymers
      increased the interaction between DNA and nanopolymers. Prepared nanopolymers
      were characterized by SEM, FT-IR and ZETA sizer analysis. Synthesized
      nanopolymers were spherical, and their average particle size was about 246.8 nm.
      Adsorption of DNA onto galactoacrylate based nanopolymers was investigated by
      using different pHs, temperatures, ionic strength, DNA concentrations and
      desorption studies and maximum DNA adsorption was found to be as 567.12 mg/g
      polymer at 25  degrees C, in pH 5.0 acetate buffer. Reusability was investigated
      for 5 successive reuse and DNA adsorption capacity decreased only about 10% at
      the end of the 5th reuse.

PMID- 28504017
TI  - Chemical composition, antioxidant and cytotoxic activities of extracts from the
      leaves of Smilax brasiliensis Sprengel (Smilacaceae).
AB  - The antioxidant and cytotoxic activities of petroleum ether and methanol
      extracts, fatty acids and methyl esters from leaves of Smilax brasiliensis were
      evaluated, and the composition of the extracts was determined. Palmitic, linoleic
      and linolenic acids were major components of the extracts. For antioxidant
      activity, all samples exhibited IC50 values lower than BHT (2,6-di-tert-butyl-4
      methylphenol). The extracts, fatty acids and methyl esters from S. brasiliensis
      presented no toxicity to larvae of the brine shrimp, Artemia salina. Among the
      purified substances, only methyl linolenate showed toxicity (LD50 = 21.47
      MUg/mL). This study showed, for the first time, the composition of petroleum
      ether and methanol extracts from S. brasiliensis leaves, as well as the
      antioxidant and cytotoxic activities of extracts, fatty acids and methyl esters.

PMID- 28504018
TI  - Comparison of modelling accuracy with and without exploiting automated optical
      monitoring information in predicting the treated wastewater quality.
AB  - Traditionally the modelling in an activated sludge process has been based on
      solely the process measurements, but as the interest to optically monitor
      wastewater samples to characterize the floc morphology has increased, in the
      recent years the results of image analyses have been more frequently utilized to
      predict the characteristics of wastewater. This study shows that the traditional
      process measurements or the automated optical monitoring variables by themselves
      are not capable of developing the best predictive models for the treated
      wastewater quality in a full-scale wastewater treatment plant, but utilizing
      these variables together the optimal models, which show the level and changes in
      the treated wastewater quality, are achieved. By this early warning, process
      operation can be optimized to avoid environmental damages and economic losses.
      The study also shows that specific optical monitoring variables are important in
      modelling a certain quality parameter, regardless of the other input variables
      available.

PMID- 28504019
TI  - Midterm Outcomes of Pharmacomechanical Thrombectomy in the Treatment of Lower
      Extremity Deep Vein Thrombosis With a Rotational Thrombectomy Device.
AB  - BACKGROUND: The purpose of this study was to assess the safety and efficacy with
      midterm outcomes of pharmacomechanical thrombectomy (PMT) performed by using a
      relatively new thrombectomy device in the treatment of lower extremity deep vein
      thrombosis (DVT). METHODS: Between February 2014 and February 2016, a total of 46
      patients with lower extremity DVT were treated with PMT by using Cleaner
      rotational thrombectomy system. Preprocedural, intraprocedural, postprocedural,
      and follow-up records of patients were collected and retrospectively analyzed.
      RESULTS: Mean age of patients was 50.5 (14.8) years, and 58.7% of them were
      female. Technical success rate of procedure was 91.3%. Mean procedure time was
      81.8 (40.3) minutes. Early clinical improvement was observed in all patients with
      successful treatment. No serious adverse event related to procedure and mortality
      was observed. Mean follow-up time was 16.0 (7.9) months. Reocclusion was observed
      in 7 (17.5%) patients during the follow-up period. Venous patency rates of
      patients at 1-, 3-, 6-, and 12-month follow-up visits were 95%, 92.5%, 89.7%, and
      79.5%, respectively. Mild, moderate, and severe postthrombotic syndrome were
      observed in 8 (20%) patients, 4 (10%) patients, and 1 (2.5%) patient,
      respectively. Postthrombotic syndrome-free survival rate was 67.5%. CONCLUSION:
      Cleaner rotational thrombectomy system appears to be safe and effective in the
      treatment of lower extremity DVT. Further larger randomized studies are needed to
      determine the long-term outcomes of this treatment modality.

PMID- 28504020
TI  - Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear
      cells: protective effects of curcumin and alpha-tocopherol.
AB  - The present study enumerates the attenuating effects of curcumin and alpha
      tocopherol against propoxur induced oxidative DNA damage in human peripheral
      blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral
      blood of healthy volunteers, and were exposed to varying concentrations of
      propoxur (0-21 MUg/ml) for 6, 12, and 24 h, and in combination with curcumin (9.2
      MUg/ml) or alpha-tocopherol (4.3 MUg/ml) or both. Cytotoxic effect of propoxur
      was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity
      of propoxur was evaluated by the measurement of reduced glutathione (GSH),
      malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels in cell
      lysate. A concentration-dependent cell death, depletion of GSH, an increase in
      the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or
      alpha-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH
      dG levels in propoxur exposed cells (p < 0.05). The results of the present study
      provide experimental evidence of involvement of oxidative stress in propoxur
      mediated genotoxicity in human PBMC and highlight the antioxidant role of
      curcumin and alpha-tocopherol following propoxur exposure.

PMID- 28504021
TI  - The Theory of Dyadic Morality: Reinventing Moral Judgment by Redefining Harm.
AB  - The nature of harm-and therefore moral judgment-may be misunderstood. Rather than
      an objective matter of reason, we argue that harm should be redefined as an
      intuitively perceived continuum. This redefinition provides a new understanding
      of moral content and mechanism-the constructionist Theory of Dyadic Morality
      (TDM). TDM suggests that acts are condemned proportional to three elements: norm
      violations, negative affect, and-importantly-perceived harm. This harm is dyadic,
      involving an intentional agent causing damage to a vulnerable patient (A->P). TDM
      predicts causal links both from harm to immorality (dyadic comparison) and from
      immorality to harm (dyadic completion). Together, these two processes make the
      "dyadic loop," explaining moral acquisition and polarization. TDM argues against
      intuitive harmless wrongs and modular "foundations," but embraces moral pluralism
      through varieties of values and the flexibility of perceived harm. Dyadic
      morality impacts understandings of moral character, moral emotion, and
      political/cultural differences, and provides research guidelines for moral
      psychology.

PMID- 28504022
TI  - Safinamide for the treatment of Parkinson's disease.
AB  - INTRODUCTION: The major unmet needs in the medical treatment of Parkinson disease
      (PD) are reduction of motor side effects from dopaminergic drugs, management of
      non-motor symptoms and disease modification. Areas covered: Motor fluctuations
      and OFF periods are a significant determinant of quality of life in PD and
      reducing their duration and severity can significantly improve motor function.
      This aim may be partly facilitated by the development of effective adjunctive
      drugs for dopamine replacement. Safinamide (Xadago), which is a first generation
      anticonvulsant, has pharmacological properties which are of interest in the
      context of neurodegenerative diseases, leading to research into its potential as
      an adjunct to levodopa in PD. Expert opinion: Although its mechanism has not been
      fully defined, safinamide provides enhanced symptom control of motor function in
      advanced PD and improves quality of life.

PMID- 28504023
TI  - Twelve tips for effective body language for medical educators.
AB  - BACKGROUND: A significant proportion of human communication is nonverbal.
      Although the fields of business and psychology have significant literature on
      effectively using body language in a variety of situations, there is limited
      literature on effective body language for medical educators. AIM: To provide 12
      tips to highlight effective body language strategies and techniques for medical
      educators. METHOD: The tips provided are based on our experiences and reflections
      as clinician-educators and the available literature. RESULTS: The 12 tips
      presented offer specific strategies to engage learners, balance learner
      participation, and bring energy and passion to teaching. CONCLUSIONS: Medical
      educators seeking to maximize their effectiveness would benefit from an
      understanding of how body language affects a learning environment and how body
      language techniques can be used to engage audiences, maintain attention, control
      challenging learners, and convey passion for a topic. Understanding and using
      body language effectively is an important instructional skill.

PMID- 28504024
TI  - Detection of driver and subclonal mutations in myelofibrosis: clinical impact on
      pharmacologic and transplant based treatment strategies.
AB  - INTRODUCTION: Myelofibrosis (MF) is the most aggressive form among Philadelphia
      negative (Ph-) myeloproliferative neoplasms (MPNs). In the last years, the
      mutational landscape of MF has expanded remarkably by the identification of
      additional recurrent mutations, called subclonal mutations. Areas covered: Here
      we describe the available data about the currently identified subclonal mutations
      and their prognostic value in MF patients. We also review the practical value of
      including such molecular information in available prognostic models for both
      outcome prediction and possibly treatment decision with regards to transplant
      indication. Lastly, we covered the available data on the application of molecular
      markers for minimal residual disease (MRD) monitoring after transplantation.
      Expert commentary: The demonstration of the prognostic value of additional
      mutations suggests to define this molecular profile at diagnosis and when an
      allogeneic transplant can be advised, particularly in younger patients. The
      presence of molecular markers might offer the possibility to evaluate the depth
      of remission and to monitor MRD after transplantation. Prospective clinical
      studies are needed to validate the use of this molecular data in the routine
      clinical practice.

PMID- 28504025
TI  - The preclinical discovery of vosaroxin for the treatment of acute myeloid
      leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) represents a disease with a very poor
      outcome and remains an area of significant unmet need necessitating novel
      therapeutic strategies. Among novel therapeutic agents, vosaroxin is a first-in
      class anticancer quinolone derivative that targets topoisomerase II and induces
      site-selective double-strand breaks in DNA, leading to tumor cell apoptosis.
      Areas covered: Herein, the authors provide a comprehensive review of the
      preclinical development of vosaroxin. This includes coverage of vosaroxin's
      mechanism of action in addition to its pharmacology and of the main studies
      reported over the past few years with vosaroxin when used to treat adult AML.
      Expert opinion: Given that vosaroxin is associated with fewer potential side
      effects, it may be of benefit to elderly patients with relapsed/refractory AML
      and to those with additional comorbidities who have previously received an
      anthracycline and cytarabine combination. Furthermore, vosaroxin also was seen to
      be active in multidrug-resistant preclinical models. However, further studies
      have to be performed to better evaluate its place in the armamentarium against
      AML.

PMID- 28504026
TI  - The influence of time horizon on results of cost-effectiveness analyses.
AB  - BACKGROUND: Debates persist on the appropriate time horizon from a payer's
      perspective and how the time horizon in cost-effectiveness analysis (CEA)
      influences the value assessment. METHODS: We systematically reviewed the Tufts
      Medical Center CEA Registry and identified US-based studies that used a payer
      perspective from 2005-2014. We classified the identified CEAs as short-term (time
      horizon <= 5 years) and long-term (> 5 years), and examined associations between
      study characteristics and the specified time horizon. We also developed case
      studies with selected interventions to further explore the relationship between
      time horizon and projected costs, benefits, and incremental cost-effectiveness
      ratios (ICER). RESULTS: Among 782 identified studies that met our inclusion
      criteria, 552 studies (71%) utilized a long-term time horizon while 198 studies
      (25%) used a short-term horizon. Among studies that employed multiple time
      horizons, the extension of the time horizon yielded more favorable ICERs in 19
      cases and less favorable ICERs in 4 cases. Case studies showed the use of a
      longer time horizon also yielded more favorable ICERs. CONCLUSION: The assumed
      time horizon in CEAs can substantially influence the value assessment of medical
      interventions. To capture all consequences, we encourage the use of time horizons
      that extend sufficiently into the future.

PMID- 28504027
TI  - Epidemiology and comorbidity of obsessive-compulsive disorder in late
      adolescence: a cross-sectional study in senior high schools in Greece.
AB  - OBJECTIVE: The aim of this study was to examine the epidemiology, comorbidity and
      use of health services of obsessive-compulsive disorder (OCD) and subclinical
      obsessive-compulsive symptoms in late adolescence. METHODS: A total of 2427
      adolescents attending senior high schools in Greece were selected for a detailed
      psychiatric interview using the revised clinical interview schedule (CIS-R). Use
      of alcohol, nicotine and cannabis, and several socio-demographic and socio
      economic variables were also assessed. RESULTS: The prevalence of OCD was 1.39%
      (95% confidence interval [CI]: 1.05-1.84) while that of subclinical obsessive
      compulsive symptoms was 2.77% (2.22-3.45). There was a female preponderance for
      subclinical symptoms. Financial difficulties of the family was the only socio
      demographic variable that was significantly associated with OCD but not with
      subclinical symptoms. The pattern of comorbidity was similar for both conditions
      but milder in the subclinical form. About one in three reported use of general
      health services and one in ten use of psychiatric services. CONCLUSIONS: OCD and
      subclinical obsessive-compulsive symptoms were relatively common. Comorbidity
      with other psychiatric disorders and use of substances was considerable even in
      subclinical status, but use of specialised health services was small. Clinical
      and research implications are discussed.

PMID- 28504028
TI  - Essential competencies in global health research for medical trainees: A
      narrative review.
AB  - INTRODUCTION: Participation in short-term educational experiences in global
      health (STEGHs) among medical trainees is increasingly accompanied by interest in
      conducting research while abroad. Because formal training in both global health
      and research methods is currently under-represented in most medical curricula,
      trainees are often unfamiliar with the knowledge, attitudes, and skills necessary
      to design and conduct research successfully. This narrative review identifies
      essential global health research competencies for medical trainees engaged in
      STEGHs. METHODS: The authors searched the literature using the terms global
      health, competency, research, research methods/process/training, scholarly
      project, medical student, and medical education/education. Because articles
      directly addressing global health research competencies for medical trainees were
      limited, the authors additionally drew on the broader literature addressing
      general research competencies and global health competencies. FINDINGS: Articles
      yielded by the literature search, combined with established guidelines in
      research ethics and global health ethics, were used to identify six core domains
      and twenty discrete competencies fundamental to global health research at a level
      appropriate for medical trainees enrolled in STEGHs. Consideration was given to
      diverse research modalities, varying levels of training, and the availability of
      mentoring and on-site support. DISCUSSION: Research may provide important
      benefits to medical trainees and host partners. These competencies provide a
      starting point; however, circumstances at any host site may necessitate
      additional competencies specific to that setting. These competencies are also
      limited by the methodology employed in their development and the need for
      additional perspectives from host partners. CONCLUSIONS: The competencies
      identified outline basic knowledge, attitudes, and skills necessary for medical
      trainees to conduct limited global health research while participating in STEGHS.
      They may also be used as a basis for curriculum development, assessment, and
      research capacity development.

PMID- 28504029
TI  - Obstetric brachial plexus palsy: a population-based retrospective case-control
      study and medicolegal considerations.
AB  - AIMS: The aim of this study was to examine 24 cases of obstetric brachial plexus
      palsy (OBPP) in 41,002 deliveries occurred at San Camillo-Forlanini Hospital in
      Rome, during the period 2000-2012. MATERIALS AND METHODS: A population-based
      retrospective case-control study was designed and the database of the hospital
      was searched; for each case, maternal and fetal records were examined and some
      risk factors were evaluated. RESULTS: A statistically significant association
      between the 24 cases OBPP and the following risk factors: primiparity (p < .014),
      birth weight (p < .002), maternal age (p < .02), diabetes (p < .03) and shoulder
      dystocia (p < .003) was found, moreover all the OBPP cases were recorded only in
      vaginal deliveries. CONCLUSIONS: The absence of OBPP cases in cesarean deliveries
      highlighted in this study supports the option of proposing an elective cesarean
      in the presence of known risk factors after a full disclosure with the mother of
      risks and benefits in order to obtain a valid consent. Furthermore, when cases of
      OBPP occur, communication between the physician and the parents of newborns is
      crucial and it may represent a valid risk-management tool to reduce malpractice
      lawsuits.

PMID- 28504030
TI  - Practical recommendations for the choice of anticoagulants in the management of
      patients with atrial fibrillation on ibrutinib.
AB  - The management of AF represents a major challenge in patients with CLL,
      especially in elderly patients with multiple comorbidities who are representative
      of the majority of patients with CLL. This is especially complex in the case of
      ibrutinib. Many anticoagulants have potential for pharmacological interaction
      with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of
      ibrutinib therapy in these patients mandates review and revision of the need for
      anticoagulation and best anticoagulant to use. Herein, we review the current
      knowledge of the metabolism of common anticoagulants and how they may interact
      with ibrutinib.

PMID- 28504031
TI  - Topical 0.25% desoximetasone spray efficacy for moderate to severe plaque
      psoriasis: a randomized clinical trial.
AB  - BACKGROUND: Traditionally, ointments were the vehicle of choice for psoriasis.
      Poor adherence of traditional vehicles limits the use of topical corticosteroids.
      Alternative formulations have gained popularity due to their ease of application,
      improved adherence and efficacy. OBJECTIVE: To evaluate the efficacy of topical
      desoximetasone 0.25% spray formulation in extensive psoriasis. METHODS: This
      multicenter, double-blinded, randomized trial compared twice daily topical 0.25%
      desoximetasone spray to placebo in subjects >=18 with moderate to severe plaque
      psoriasis. Primary outcome of the study was the proportion of subjects in each
      group that achieved clinical success (Physician Global Assessment [PGA] of 0 or
      1) and/or treatment success at (target lesion score of 0 or 1) day 28. RESULTS:
      One-hundred-and-twenty subjects were enrolled. At baseline, 75.0% and 73.3% of
      the treatment and placebo group had at least moderate PGA, respectively. Clinical
      success in the intended-to treat and placebo group was 30% and 5% (p = .0003),
      respectively; treatment success was 39% and 7% (p < .0001), respectively.
      LIMITATIONS: The lack of standardized outcomes for topical psoriasis treatments
      limits the ability to compare the results to other treatments. CONCLUSIONS:
      Topical desoximetasone spray provides rapid control of moderate to severe
      psoriasis lesions and may be considered for patients awaiting approval of
      biologicals. TRIAL REGISTRATION: Clinical Trial was registered at
      clinicaltrial.gov: NCT01206387.

PMID- 28504032
TI  - Targeting peroxisome proliferator-activated receptors: a novel strategy for
      Philadelphia chromosome-positive leukemia cells.

PMID- 28504033
TI  - Salvage chemotherapy and autologous stem cell transplantation for peripheral T
      cell lymphoma: a subset analysis of the Canadian Cancer Trials Group LY.12
      randomized phase 3 study.
AB  - Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy. Of the 619
      patients with relapsed and refractory (R/R) aggressive lymphoma enrolled in the
      Canadian Cancer Trials Group LY.12 phase 3 trial, 59 (9.5%) had PTCL. Among
      these, 81% had advanced stage disease, 41% had an International Prognostic Score
      >=3, and 41% were refractory to primary therapy. Within the PTCL cohort, the
      overall response rate after two cycles of salvage chemotherapy was 36%; no
      difference was observed between dexamethasone, cytarabine, cisplatin (10/30,
      33%), and gemcitabine, cisplatin, dexamethasone (11/29, 38%) therapy. At one
      year, event-free survival (EFS) was 16% and overall survival (OS) was 28%. For
      PTCL patients, who received autologous stem cell transplant, two-year EFS and OS
      were 21% and 42%, respectively. Patients with PTCL had inferior OS (HR 0.49, p <
      .0001) and EFS (HR 0.53, p < .0001) compared to B-cell lymphoma. Outcomes for
      patients with R/R PTCL are poor with currently available therapies.

PMID- 28504034
TI  - A simulation of loading doses for vancomycin continuous infusion regimens in
      intensive care.
AB  - BACKGROUND: Delayed achievement of target vancomycin serum concentrations may
      adversely affect clinical outcomes. The objective of this retrospective study was
      to compare the prediction accuracy of different body weight descriptors for
      volume of distribution and to propose an optimal loading dose (LD) for continuous
      infusion regimens in adults. METHODS: Pharmacokinetic variables were computed
      using one-compartmental analysis. Simulated LDs of vancomycin were evaluated for
      each patient. RESULTS: Volume of distribution, clearance, and half-life median
      values (interquartile range) for vancomycin in the study population (n = 30) were
      0.45 (0.39-0.61) L.kg-1, 0.026 (0.015-0.040) L.h-1.kg-1, and 10.3 (7.7-21.3) h,
      respectively. The observed volume of distribution was better predicted by total
      body weight (TBW) than by the ideal body weight or the adjusted body weight.
      CONCLUSIONS: An LD of 10.7 mg per kg TBW was optimal in our study population.
      Using this LD, 17.9% of simulated vancomycin serum levels were just below the
      therapeutic range, only 10.7% concentrations exceeded the target range and no
      concentration was toxic. The use of a LD would lead to reduced median time to
      reach target concentrations from 17 to 1 h.

PMID- 28504035
TI  - Bleomycin pulmonary toxicity does not adversely affect the outcome of patients
      with Hodgkin lymphoma.
AB  - Bleomycin pulmonary toxicity (BPT) is a well-described complication of bleomycin
      containing regimens. Previous data on risk factors and the impact of BPT on
      survival in Hodgkin lymphoma (HL) were conflicting. We reviewed 253 HL patients
      treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) at the
      Princess Margaret Hospital from 1999 to 2009 to examine the incidence and risk
      factors for BPT, and the effect of BPT on survival. BPT was defined by pulmonary
      symptoms, bilateral interstitial infiltrates on computed tomography, and the
      absence of infection. Kaplan-Meier estimates were used to compare overall
      survival (OS) and progression-free survival (PFS) between groups. The incidence
      of BPT was low (11%). Age >=45 (OR = 2.5) and granulocyte colony-stimulating
      factor use (OR = 3.6) were identified as predictors of BPT on multivariable
      logistic models. At a follow-up of 5 years, OS and PFS were 88% and 82%,
      respectively. Neither BPT nor bleomycin discontinuation had significant impact on
      survival outcomes.

PMID- 28504036
TI  - Combination therapy of BRAF inhibitors for advanced melanoma with BRAF V600
      mutation: a systematic review and meta-analysis.
AB  - BACKGROUND: Although BRAF inhibitors have been used to treat advanced melanoma
      with BRAF mutation, combination strategies are suggested due to acquired
      resistance to BRAF inhibitors. OBJECTIVE: To assess the efficacy of BRAF
      inhibitor-based combination therapy for the treatment of advanced melanoma with
      BRAF mutation. METHODS: We conducted a systematic review and meta-analysis of
      studies that compared BRAF inhibitor-based combination therapy with BRAF
      inhibitor monotherapy. We searched MEDLINE, EMBASE, the Cochrane Library and
      relevant conference proceedings. The random-effects inverse variance and Mantel
      Haenszel methods were used to pool the results. RESULTS: Four randomized
      controlled trials and one cohort study were identified. A combination therapy
      with BRAF inhibitors and MEK inhibitors was used in all studies. The combined
      hazard ratios of overall survival (OS) and progression-free survival (PFS)
      comparing combination therapy with monotherapy were 0.70 [95% confidence interval
      (CI) 0.62-0.78] and 0.59 (95% CI 0.55-0.63), respectively. The combined risk
      ratio of objective response rate (ORR) was 1.30 (95% CI 1.20-1.40), which meant
      more patients achieved complete/partial responses in combination therapy group
      than those in the monotherapy group. CONCLUSIONS: Combination therapy with BRAF
      inhibitors and MEK inhibitors significantly improved OS, PFS, and ORR in patients
      with advanced melanoma with BRAF mutation.

PMID- 28504038
TI  - Corrigendum to "Monitoring the World Health Organization Global Target 2025 for
      exclusive breastfeeding: Experience from the United States".

PMID- 28504037
TI  - Plasma butyrylcholinesterase activity: a possible biomarker for differential
      diagnosis between Alzheimer's disease and dementia with Lewy bodies?
AB  - Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for
      secondary hydrolysis of the acetylcholine. K and -116A BCHE variants were
      associated with decrease in plasma BChE activity, and their influence has been
      investigated in diseases with a cholinergic deficit such as Alzheimer's disease
      (AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE
      genetic variants on enzymatic activity, all patients and controls were genotyped
      for K and -116A variants. We found lower plasma BChE activity in DLB patients
      compared to elderly controls and to AD independent of the presence of K or -116A
      variants. Our results suggest that the reduction of total plasma BChE activity is
      probably associated with a feedback mechanism and provides a future perspective
      of using this enzyme as a possible plasmatic marker for differential diagnosis
      between AD and DLB.

PMID- 28504039
TI  - Frozen bereavement.

PMID- 28504040
TI  - Facebook addiction and loneliness in the post-graduate students of a university
      in southern India.
AB  - BACKGROUND: Facebook is a social networking site (SNS) for communication,
      entertainment and information exchange. Recent research has shown that excessive
      use of Facebook can result in addictive behavior in some individuals. AIM: To
      assess the patterns of Facebook use in post-graduate students of Yenepoya
      University and evaluate its association with loneliness. METHODS: A cross
      sectional study was done to evaluate 100 post-graduate students of Yenepoya
      University using Bergen Facebook Addiction Scale (BFAS) and University of
      California and Los Angeles (UCLA) loneliness scale version 3. Descriptive
      statistics were applied. Pearson's bivariate correlation was done to see the
      relationship between severity of Facebook addiction and the experience of
      loneliness. RESULTS: More than one-fourth (26%) of the study participants had
      Facebook addiction and 33% had a possibility of Facebook addiction. There was a
      significant positive correlation between severity of Facebook addiction and
      extent of experience of loneliness ( r = .239, p = .017). CONCLUSION: With the
      rapid growth of popularity and user-base of Facebook, a significant portion of
      the individuals are susceptible to develop addictive behaviors related to
      Facebook use. Loneliness is a factor which influences addiction to Facebook.

PMID- 28504043
TI  - Insight in psychosis: Standards, science, ethics and value judgment.
AB  - BACKGROUND: The clinical assessment of insight solely employs biomedical
      perspectives and criteria to the complete exclusion of context and culture and to
      the disregard of values and value judgments. AIM: The aim of this discussion
      article is to examine recent research from India on insight and explanatory
      models in psychosis and re-examine the framework of assessment, diagnosis and
      management of insight and explanatory models. METHODS: Recent research from India
      on insight in psychosis and explanatory models is reviewed. RESULTS: Recent
      research, which has used longitudinal data and adjusted for pretreatment
      variables, suggests that insight and explanatory models of illness at baseline do
      not predict course, outcome and treatment response in schizophrenia, which seem
      to be dependent on the severity and quality of the psychosis. It supports the
      view that people with psychosis simultaneously hold multiple and contradictory
      explanatory models of illness, which change over time and with the trajectory of
      the illness. It suggests that insight, like all explanatory models, is a
      narrative of the person's reality and a coping strategy to handle with the varied
      impact of the illness. CONCLUSION: This article argues that the assessment of
      insight necessarily involves value entailments, commitments and consequences. It
      supports a need for a broad-based approach to assess awareness, attribution and
      action related to mental illness and to acknowledge the role of values and value
      judgment in the evaluation of insight in psychosis.

PMID- 28504044
TI  - Epigenetics and developmental psychiatry.

PMID- 28504046
TI  - Formulation and characterization of Phospholipon 90 G and tween 80 based
      transfersomes for transdermal delivery of eprosartan mesylate.
AB  - The objective of the current study was to formulate the eprosartan mesylate
      loaded transfersomes using different proportions of Phospholipon(r) 90 G and
      Tween(r) 80 (95-75:5-25% w/w). The prepared transfersomes were characterized for
      their vesicles size, shape, polydispersity index, zeta potential, entrapment
      efficiency, in vitro skin permeation, confocal laser scanning microscopy, and in
      vivo skin irritation. Results revealed that the formulated transfersomes were
      negatively charged, spherical unilamellar structure of 71.18-85.66 nm with
      entrapment efficiency of 83.00-88.19%, and presented transdermal flux of 1.78
      5.02 MUg/cm2/h across rat skin. Confocal laser scanning microscopy confirmed that
      the formulated rhodamine 6 G loaded transfersomes could penetrate deeply and
      uniformly into rat skin. Additionally, in vivo skin irritation studies revealed
      that the prepared transfersomes were devoid of any skin irritation potential
      (erythema and edema). Results of this study revealed that the transfersomes
      prepared with Tween(r) 80 could be used to enhance the transdermal delivery of
      eprosartan mesylate. In conclusion, transdermal transfersomes formulation may
      prove to be an encouraging drug carrier for eprosartan mesylate and other
      actives, particularly owing to their simple formulation and unsophisticated scale
      up methods.

PMID- 28504047
TI  - Intravascular Ultrasound Validation of Contemporary Angiographic Scores
      Evaluating the Severity of Calcification in Peripheral Arteries.
AB  - PURPOSE: To validate 3 angiographic scoring systems for peripheral artery
      calcification using intravascular ultrasound (IVUS) as the gold standard.
      METHODS: The study employed preprocedure angiography and IVUS data from 47
      patients (median age 72 years; 34 men) in the 55-patient JetStream G3 Calcium
      Study ( ClinicalTrials.gov identifier NCT01273623) to validate the 3 angiographic
      scoring systems [Peripheral Academic Research Consortium (PARC), Peripheral
      Arterial Calcium Scoring System (PACSS), and the DEFINITIVE Ca++ trial].
      Preprocedure angiograms were analyzed using conventional quantitative vessel
      analysis software in 2 orthogonal views. Calcium length was evaluated by markers
      placed beside the artery during the procedure; calcium deposit(s) were assessed
      as being on one or both sides of the vessel wall. The 3 calcium scoring systems
      used these 2 basic angiographic elements to evaluate calcium severity. Based on
      these criteria, calcium severity varied from none to focal, mild, moderate, or
      severe in PARC; grade 0 to 4 in PACSS; and none, moderate, or severe in the
      DEFINITIVE Ca++ system. Calcium location on IVUS was classified as superficial,
      deep, or mixed. Lesion length was the segment between the most normal looking
      proximal and distal reference sites. Superficial, deep, and calcium length were
      based on motorized IVUS pullback. RESULTS: IVUS detected calcium in 44/47 (93.6%)
      lesions, and angiography detected calcium in 26/47 (55.3%) lesions (p<0.001). The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of angiography relative to IVUS were 59%, 100%, 100%, and 14%,
      respectively. With increasing severity of angiographic calcium, there was a
      stepwise increase in the prevalence of IVUS superficial calcium and the maximum
      arc and length of superficial calcium. Using PARC criteria, with increasing
      severity of calcification, IVUS maximum calcium arc increased from 120 degrees 
      for none to 305 degrees  for severe (p<0.001); the length of calcium increased
      from 7 to 68 mm (p<0.001). Though a similar trend was seen in IVUS superficial
      calcium, it was not observed in IVUS deep calcium. Similar observations were seen
      when using the PACSS and DEFINITIVE Ca++ scoring systems. CONCLUSION: IVUS
      confirmed that the PARC, PACSS, and DEFINITIVE Ca++ calcium scoring systems can
      be used to classify the degree of calcium in peripheral artery disease,
      especially superficial calcium.

PMID- 28504048
TI  - The Penn State Heart Assistant: A pilot study of a web-based intervention to
      improve self-care of heart failure patients.
AB  - The Penn State Heart Assistant, a web-based, tablet computer-accessed, secure
      application was developed to conduct a proof of concept test, targeting patient
      self-care activities of heart failure patients including daily medication
      adherence, weight monitoring, and aerobic activity. Patients (n = 12) used the
      tablet computer-accessed program for 30 days-recording their information and
      viewing a short educational video. Linear random coefficient models assessed the
      relationship between weight and time and exercise and time. Good medication
      adherence (66% reporting taking 75% of prescribed medications) was reported.
      Group compliance over 30 days for weight and exercise was 84 percent. No
      persistent weight gain over 30 days, and some indication of weight loss (slope of
      weight vs time was negative (-0.17; p value = 0.002)), as well as increased
      exercise (slope of exercise vs time was positive (0.08; p value = 0.04)) was
      observed. This study suggests that mobile technology is feasible, acceptable, and
      has potential for cost-effective opportunities to manage heart failure patients
      safely at home.

PMID- 28504049
TI  - Knowing when to hold 'em: regret and the relation between missed opportunities
      and risk taking in children, adolescents and adults.
AB  - Regret over missed opportunities leads adults to take more risks. Given recent
      evidence that the ability to experience regret impacts decisions made by 6-year
      olds, and pronounced interest in the antecedents to risk taking in adolescence,
      we investigated the age at which a relationship between missed opportunities and
      risky decision-making emerges, and whether that relationship changes at different
      points in development. Six- and 8-year-olds, adolescents and adults completed a
      sequential risky decision-making task on which information about missed
      opportunities was available. Children also completed a task designed to measure
      their ability to report regret when explicitly prompted to do so. The
      relationship between missed opportunities and risky decision-making did not
      emerge until 8 years, at which age it was associated with the ability to
      explicitly report regret, and was stronger in adults than in adolescents. These
      novel results highlight the potential importance of the ability to experience
      regret in children and adolescents' risky decision-making.

PMID- 28504050
TI  - How long is sufficient for optimal neuroprotection with cerebral cooling after
      ischemia in fetal sheep?
AB  - The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic
      ischemic encephalopathy is surprisingly unclear. This study assessed the relative
      efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received
      sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia
      (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia
      was associated with profound loss of electroencephalogram (EEG) power, neurons in
      the cortex and hippocampus, and oligodendrocytes and myelin basic protein
      expression in the white matter, with increased Iba-1-positive microglia and
      proliferation. Hypothermia for 48 h was associated with improved outcomes
      compared to normothermia, but a progressive deterioration of EEG power after
      rewarming compared to 72 h of hypothermia, with impaired neuronal survival and
      myelin basic protein, and more microglia in the white matter and cortex. These
      findings show that head cooling for 48 h is partially neuroprotective, but is
      inferior to cooling for 72 h after cerebral ischemia in fetal sheep. The close
      association between rewarming at 48 h, subsequent deterioration in EEG power and
      increased cortical inflammation strongly suggests that deleterious inflammation
      can be reactivated by premature rewarming.

PMID- 28504051
TI  - Modeling qRT-PCR dynamics with application to cancer biomarker quantification.
AB  - Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is widely
      used for molecular diagnostics and evaluating prognosis in cancer. The utility of
      mRNA expression biomarkers relies heavily on the accuracy and precision of
      quantification, which is still challenging for low abundance transcripts. The
      critical step for quantification is accurate estimation of efficiency needed for
      computing a relative qRT-PCR expression. We propose a new approach to estimating
      qRT-PCR efficiency based on modeling dynamics of polymerase chain reaction
      amplification. In contrast, only models for fluorescence intensity as a function
      of polymerase chain reaction cycle have been used so far for quantification. The
      dynamics of qRT-PCR efficiency is modeled using an ordinary differential equation
      model, and the fitted ordinary differential equation model is used to obtain
      effective polymerase chain reaction efficiency estimates needed for efficiency
      adjusted quantification. The proposed new qRT-PCR efficiency estimates were used
      to quantify GUCY2C (Guanylate Cyclase 2C) mRNA expression in the blood of
      colorectal cancer patients. Time to recurrence and GUCY2C expression ratios were
      analyzed in a joint model for survival and longitudinal outcomes. The joint model
      with GUCY2C quantified using the proposed polymerase chain reaction efficiency
      estimates provided clinically meaningful results for association between time to
      recurrence and longitudinal trends in GUCY2C expression.

PMID- 28504052
TI  - Adenosine A2A receptor agonists with potent antiplatelet activity.
AB  - Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301)
      have been evaluated as new antiplatelet agents. In addition, radioligand-binding
      studies and receptor-docking experiments were performed in order to explain their
      differential biological effects on a molecular level. Among the tested adenosine
      derivatives, PSB-15826 was the most potent compound to inhibit platelet
      aggregation (EC50 0.32 +/- 0.05 umol/L) and platelet P-selectin cell-surface
      localization (EC50 0.062 +/- 0.2 umol/L), and to increase intraplatelets cAMP
      levels (EC50 0.24 +/- 0.01 umol/L). The compound was more active than CGS21680
      (EC50 0.97+/-0.07 umol/L) and equipotent to NECA (EC50 0.31 +/- 0.05 umol/L) in
      platelet aggregation induced by ADP. In contrast to the results from cAMP assays,
      Ki values determined in radioligand-binding studies were not predictive of the
      A2A agonists' antiplatelet activity. Docking studies revealed the key molecular
      determinants of this new family of adenosine A2A receptor agonists: differences
      in activities are related to pi-stacking interactions between the ligands and the
      residue His264 in the extracellular loop of the adenosine A2A receptor which may
      result in increased residence times. In conclusion, these results provide an
      improved understanding of the requirements of antiplatelet adenosine A2A receptor
      agonists.

PMID- 28504053
TI  - Improved antifouling potential of polyether sulfone polymeric membrane containing
      silver nanoparticles: self-cleaning membranes.
AB  - A new strategy to enhance the antifouling potential of polyether sulfone (PES)
      membrane is presented. Chemically synthesized silver nanoparticles (AgNPs) were
      used to prepare a mixed-matrix PES membrane by the phase inversion technique.
      Primarily, AgNPs synthesis was confirmed by surface plasmon resonance at 410-430
      nm using UV-Visible spectroscopy. X-ray diffraction analysis revealed that AgNPs
      were crystalline with a diameter of 21 +/- 2 nm. Furthermore, PES membranes were
      characterized by energy dispersive X-ray spectroscopy to confirm the
      incorporation of AgNPs in membranes. Hydrophilicity of the membranes was
      enhanced, whereas roughness, mechanical strength and biofouling were relatively
      reduced after embedding the AgNPs. Antibacterial potential of AgNPs was evaluated
      for E. coli in the disc diffusion and colony-forming unit (CFU) count method. All
      of the membranes were assessed for antifouling activity by filtering a control
      dilution (106 CFU/ml) of E. coli and by counting CFU. Anti-biofouling activity of
      the membrane was observed with different concentrations of AgNPs. Maximum
      reduction (66%) was observed in membrane containing 1.5% of AgNPs. The addition
      of antibiotic ceftriaxone enhanced the antibacterial effect of AgNPs in PES
      membranes. Our practicable antifouling strategy may be applied to other polymeric
      membranes which may pave the new way to achieve sustainable and self-cleaning
      membrane reactors on large scale.

PMID- 28504054
TI  - Exploring the challenges in obtaining physical activity data from women using hip
      worn accelerometers.
AB  - Quality objective physical activity data are required to inform physical activity
      based health improvement initiatives, however, various challenges undermine
      acquisition of such data. We examined the efficacy and challenges of a hip-worn
      accelerometry protocol in women. Specific objectives included determining
      accelerometer-wear-compliance rates and understanding the barriers and
      acceptability of wearing accelerometers. Healthy New Zealand women (n = 406) of
      three ethnicities (Maori (indigenous New Zealander), Pacific, European) aged 16
      45 years (30.9 +/- 8.7 y) wore hip-mounted Actigraph wGT3X+ accelerometers for 7
      consecutive days under a 24-h wear protocol. Post hoc, a sub-sample (n = 45; age:
      29.4 +/- 9.0 y) was interviewed to investigate comfort/convenience and burdens of
      accelerometer-wear. Wear-compliance (>=10 h/day, >=4 day) was 86%. European women
      returned more valid data (92.7%, p < .04) than Pacific (73.0%) or Maori women
      (82.1%). Twenty-two participants (5.4%) had completely missing data; 13 due to
      lost accelerometers. Burden of accelerometer-wear was greatest during sleeping
      (66.7%) due to discomfort. Embarrassment of accelerometer visibility through
      clothing and consequent restricted clothing choices caused high burden in social
      settings (45.2%). Discomfort during sleeping, embarrassment due to perceived
      appearance in social settings and ethnicity are key factors affecting the
      efficacy of collecting physical activity data from women using hip-worn
      accelerometers. Refining accelerometer design to reduce size and subsequently
      participant burden should improve acceptability and wear-compliance. Increasing
      overall participant compliance by reducing burden and ensuring appropriate
      understanding of study aims and relevance should reduce attrition and improve
      wear-compliance and data quality when collecting accelerometry data from women of
      different ethnicities.

PMID- 28504056
TI  - Corrigendum.

PMID- 28504055
TI  - Severe generalised chondrodysplasia in miniature cattle breeds.

PMID- 28504057
TI  - Molecular dynamic modeling of CYP51B in complex with azole inhibitors.
AB  - Cytochrome P450 14alpha-sterol demethylase (CYP51), the key enzyme in sterol
      biosynthesis pathway, is an important target protein of cholesterol-lowering
      agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51
      family members. In the present study, we have chosen four representative
      inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb),
      and voriconazole (Vor), and launched to investigate the binding features of
      CYP51B-inhibitor and gating characteristics via molecular docking and molecular
      dynamics (MD) simulations. The results show that the ranking of binding
      affinities among these inhibitors is Din > Teb > Vor > Flu. Din shows the
      strongest binding affinity, whereas Flu shows the weakest binding affinity. More
      importantly, based on the calculated binding free energy results, we hypothesize
      that the nonpolar interactions are the most important contributors, and three key
      residues (Thr77, Ala258, and Lys454) play crucial role in protein-inhibitor
      binding. Besides, residue Phe180 may play a molecular switch role in the process
      of the CYP51B-Teb and CYP51B-Vor binding. Additionally, Tunnel analysis results
      show that the major tunnel of Din, Flu, and Teb is located between helix K, FG
      loop, and beta4 hairpin (Tunnel II).The top ranked possible tunnel (Tunnel II)
      corresponds to Vor exits through helix K, F and helix J. This study further
      revealed the CYP51B relevant structural characteristics at the atomic level as
      well as provided a basis for rational design of new and more efficacious
      antifungal agents.

PMID- 28504058
TI  - South Korean anthropometric data and survey methodology: 'Size Korea' project.
AB  - Considering the many emerging markets in East Asia, access to contemporary
      anthropometric data for this region is important for designers and manufacturers
      seeking to produce the best fitting products and living environments for
      consumers. The purpose of this paper is to describe Korean anthropometric data
      collection and survey techniques for those who are interested in ethnic
      characteristics, conducting surveys, and formulating ergonomic product designs
      for South Korean and, more broadly, East Asian populations. The Size Korea survey
      was conducted in 2003-2004 and 2010. A total of 14,200 civilians aged 0-90 years
      participated in the survey, with 119 body and weight dimensions measured in 2004.
      Twenty new dimensions from Inbody measurement were added in 2010 and the data
      were continuously updated. We referred to ISO 7250, 8559 and 15535 to ensure
      validity and reliability. Fifty major body dimensions, including weight, are
      summarised in this paper, and 34 of these dimensions can be compared with 11
      multinational data already reported  in other publications. Practitioner Summary:
      This paper presents the up-to-date anthropometric database of East Asian physical
      characteristics and survey methodology. These data satisfy the ISO standards and
      comprise 50 physical dimensions including weight. Thirty-four dimensions of these
      can be directly compared with available multinational data.

PMID- 28504059
TI  - Coupled microalgal cultivation with the treatment of domestic sewage and high
      level CO2.
AB  - The ability of Scenedesmus quadricauda SDEC-13 to accumulate biomass and remove
      nutrients in domestic sewage from campus when incorporated with 15% CO2 was
      explored. The maximum specific growth rate, biomass productivity, biomass
      concentration, and CO2 fixation rate were 0.14 d-1, 0.08 g/L/d, 0.69 g/L, and
      0.076 g-CO2/L/d, respectively. The lipid content of SDEC-13 at different culture
      phases was also evaluated and it increased following nutrient limitation. The
      removal efficiencies of total nitrogen, total phosphorus, nitrate, and ammonium
      were all above 90%. A coupled system was designed with hydraulic retention time
      of 8.33 d and biomass harvest ratio of 12%, which could yield 0.54 g/L biomass
      and 25% lipid content with efficient domestic sewage treatment.

PMID- 28504060
TI  - Responding to the support needs of front-line public health nurses who work with
      vulnerable families and children: a qualitative study.
AB  - BACKGROUND: This paper reports on a research study to inform the development of a
      specialist role to support front line public health nurses (PHNs) working with
      vulnerable families and at risk children in Ireland. AIMS: This study aimed to
      investigate the position of a leading role and explore the implications of such
      change. METHODS: Focus group and semi-structured individual interviews were
      conducted with ten purposively selected participants in public health nursing,
      social work and a non-governmental children's organisation working in
      disadvantaged areas in Dublin. RESULTS: Assistant directors of public health
      nursing are in a key position to inform decisions regarding the children's
      services. CONCLUSION: Access to support and appropriate supervision are
      fundamental resource requirements for PHNs who work with vulnerable families and
      at risk children. The introduction of a specialist-leading role to support these
      PHN's is essential to sustaining best practice.

PMID- 28504063
TI  - The 21st Century Cures Act and the Future of Health Education and Health-Related
      Behavioral Research.

PMID- 28504062
TI  - The Health Promoting Schools Framework: Known Unknowns and an Agenda for Future
      Research.
AB  - The World Health Organization's Health Promoting Schools (HPS) framework is a
      whole-school approach to promoting health that recognizes the intrinsic
      relationship between health and education. Our recent Cochrane systematic review
      found HPS interventions produced improvements in a number of student health
      outcomes. Here we reflect on what this review was not able to tell us: in other
      words, what evidence is missing with regard to the HPS approach. Few HPS
      interventions engage with schools' "core business" by examining impacts on
      educational outcomes. Current evidence is dominated by obesity interventions,
      with most studies conducted with children rather than adolescents. Evidence is
      lacking for outcomes such as mental or sexual health, substance use, and
      violence. Activities to engage families and communities are currently weak and
      unlikely to prompt behavioral change. The HPS approach is largely absent in low
      income settings, despite its potential in meeting children's basic health needs.
      Intervention theories are insufficiently complex, often ignoring upstream
      determinants of health. Few studies provide evidence on intervention
      sustainability or cost-effectiveness, nor in-depth contextual or process data. We
      set out an agenda for future school health promotion research, considering
      implications for key stakeholders, namely, national governments, research
      funders, academics, and schools.

PMID- 28504065
TI  - Lawrence W. Green Paper of the Year Award.

PMID- 28504064
TI  - Implications of the 21st Century Cures Act for the Behavioral and Social Sciences
      at the National Institutes of Health.
AB  - The 21st Century Cures Act provides funding for key initiatives relevant to the
      behavioral and social sciences and includes administrative provisions that
      facilitate health research and increase the privacy protections of research
      participants. At about the same time as the passage of the Act, the National
      Institutes of Health Office of Behavioral and Social Sciences Research released
      its Strategic Plan 2017-2021, which addresses three scientific priorities: (a)
      improve the synergy of basic and applied behavioral and social sciences research;
      (b) enhance and promote the research infrastructure, methods, and measures needed
      to support a more cumulative and integrated approach to behavioral and social
      sciences; and (c) facilitate the adoption of behavioral and social sciences
      research findings in health research and in practice. This commentary describes
      the implications of the Cures Act on these scientific priorities and on the
      behavioral and social sciences more broadly.

PMID- 28504066
TI  - The Association of Recreational and Competitive Running With Hip and Knee
      Osteoarthritis: A Systematic Review and Meta-analysis.
AB  - Study Design Systematic review and meta-analysis. Background Running is a healthy
      and popular activity worldwide, but data regarding its association with
      osteoarthritis (OA) are conflicting. Objectives To evaluate the association of
      hip and knee OA with running and to explore the influence of running intensity on
      this association. Methods PubMed, Embase, and Cochrane Library databases were
      used to identify studies investigating the occurrence of OA of the hip and/or
      knee among runners. A meta-analysis of studies comparing this occurrence between
      runners and controls (sedentary, nonrunning individuals) was conducted. Runners
      were regarded as "competitive" if they were reported as professional/elite
      athletes or participated in international competitions. Recreational runners were
      individuals running in a nonprofessional (amateur) context. The prevalence rate
      and odds ratio (with 95% confidence interval [CI]) for OA between runners (at
      competitive and recreational levels) and controls were calculated. Subgroup
      analyses were conducted for OA location (hip or knee), sex, and years of exposure
      to running (less or more than 15 years). Results Twenty-five studies (n = 125810
      individuals) were included and 17 (n = 114829 individuals) were meta-analyzed.
      The overall prevalence of hip and knee OA was 13.3% (95% CI: 11.6%, 15.2%) in
      competitive runners, 3.5% (95% CI: 3.4%, 3.6%) in recreational runners, and 10.2%
      (95% CI: 9.9%, 10.6%) in controls. The odds ratio for hip and/or knee OA in
      competitive runners was higher than that in recreational runners (1.34; 95% CI:
      0.97, 1.86 and 0.86; 95% CI: 0.69, 1.07, respectively; controls as reference
      group; for difference, P<.001). Exposure to running of less than 15 years was
      associated with a lower association with hip and/or knee OA compared with
      controls (OR = 0.6; 95% CI: 0.49, 0.73). Conclusion Recreational runners had a
      lower occurrence of OA compared with competitive runners and controls. These
      results indicated that a more sedentary lifestyle or long exposure to high-volume
      and/or high-intensity running are both associated with hip and/or knee OA.
      However, it was not possible to determine whether these associations were
      causative or confounded by other risk factors, such as previous injury. Level of
      Evidence Etiology/harm, level 2a. J Orthop Sports Phys Ther 2017;47(6):373-390.
      doi:10.2519/jospt.2017.7137.

PMID- 28504067
TI  - Effectiveness of Inclusion of Dry Needling in a Multimodal Therapy Program for
      Patellofemoral Pain: A Randomized Parallel-Group Trial.
AB  - Study Design Randomized controlled trial. Background Evidence suggests that
      multimodal interventions that include exercise therapy may be effective for
      patellofemoral pain (PFP); however, no study has investigated the effects of
      trigger point (TrP) dry needling (DN) in people with PFP. Objectives To compare
      the effects of adding TrP DN to a manual therapy and exercise program on pain,
      function, and disability in individuals with PFP. Methods Individuals with PFP (n
      = 60) recruited from a public hospital in Valencia, Spain were randomly allocated
      to manual therapy and exercises (n = 30) or manual therapy and exercise plus TrP
      DN (n = 30). Both groups received the same manual therapy and strengthening
      exercise program for 3 sessions (once a week for 3 weeks), and 1 group also
      received TrP DN to active TrPs within the vastus medialis and vastus lateralis
      muscles. The pain subscale of the Knee injury and Osteoarthritis Outcome Score
      (KOOS; 0-100 scale) was used as the primary outcome. Secondary outcomes included
      other subscales of the KOOS, the Knee Society Score, the International Knee
      Documentation Committee Subjective Knee Evaluation Form (IKDC), and the numeric
      pain-rating scale. Patients were assessed at baseline and at 15-day
      (posttreatment) and 3-month follow-ups. Analysis was conducted with mixed
      analyses of covariance, adjusted for baseline scores. Results At 3 months, 58
      subjects (97%) completed the follow-up. No significant between-group differences
      (all, P>.391) were observed for any outcome: KOOS pain subscale mean difference, 
      2.1 (95% confidence interval [CI]: -4.6, 0.4); IKDC mean difference, 2.3 (95% CI:
      -0.1, 4.7); knee pain intensity mean difference, 0.3 (95% CI: -0.2, 0.8). Both
      groups experienced similar moderate-to-large within-group improvements in all
      outcomes (standardized mean differences of 0.6 to 1.1); however, only the KOOS
      function in sport and recreation subscale surpassed the prespecified minimum
      important change. Conclusion The current clinical trial suggests that the
      inclusion of 3 sessions of TrP DN in a manual therapy and exercise program did
      not result in improved outcomes for pain and disability in individuals with PFP
      at 3-month follow-up. Level of Evidence Therapy, level 1b. Prospectively
      registered July 27, 2015 at www.clinicaltrials.gov (NCT02514005). J Orthop Sports
      Phys Ther 2017;47(6):392-401. doi:10.2519/jospt.2017.7389.

PMID- 28504069
TI  - Population healthcare: the third dimension.

PMID- 28504068
TI  - Psychometric Properties of the Deep Muscle Contraction Scale for Assessment of
      the Drawing-in Maneuver in Patients With Chronic Nonspecific Low Back Pain.
AB  - Study Design A prospective cohort study. Background Motor control dysfunctions
      have been commonly reported in patients with chronic nonspecific low back pain
      (LBP). Physical therapists need clinical tools with adequate psychometric
      properties to assess such patients in clinical practice. The deep muscle
      contraction (DMC) scale is a clinical rating scale for assessing patients'
      ability to voluntarily contract deep abdominal muscles. Objectives To investigate
      the intrarater reliability, floor and ceiling effects, internal and external
      responsiveness, and correlation analysis (with ultrasound measures) of the DMC
      scale in patients with chronic nonspecific LBP undergoing a lumbar stabilization
      exercise program. Methods Sixty-two patients with chronic nonspecific LBP were
      included. At baseline, self-report questionnaires were administered to patients
      and a trained assessor evaluated abdominal muscle recruitment with the DMC scale
      and ultrasound imaging. Four ratios of the change in abdominal muscle thickness
      between the resting and contracted states were calculated through the ultrasound
      measures. After 1 week, the same ultrasound measures and DMC scale were collected
      again for the reliability analysis. The proportions of patients with the lowest
      and highest scores on the DMC scale were calculated to investigate floor and
      ceiling effects. All patients underwent a lumbar stabilization program,
      administered twice a week for 8 weeks. After the treatment period, all measures
      were collected again, with the addition of the global perceived effect scale, to
      assess the internal and external responsiveness of the measures. Correlation
      coefficients between ultrasound ratios and DMC scale total and subscale scores
      were also calculated. Results The intrarater reliability of the DMC scale and the
      4 ratios of abdominal muscle thickness varied from moderate to excellent. The DMC
      scale showed no floor or ceiling effects. Results for internal responsiveness of
      the DMC scale showed large effect sizes (2.26; 84% confidence interval [CI]:
      2.06, 2.45), whereas the external responsiveness was below the proposed threshold
      (area under the curve = 0.54; 95% CI: 0.39, 0.68). Fair and significant
      correlations between some ultrasound ratios and DMC subscales were found.
      Conclusion The DMC scale was demonstrated to be a reliable tool, with no ceiling
      and floor effects, and to detect change in the ability to contract the deep
      abdominal muscles after a lumbar stabilization exercise program, but with low
      accuracy for estimating patient-perceived clinical outcome. J Orthop Sports Phys
      Ther 2017;47(6):432-441. doi:10.2519/jospt.2017.7140.

PMID- 28504072
TI  - 'Pragmatic' and 'explanatory' attitudes to randomised trials.

PMID- 28504070
TI  - Adverse effects on health and wellbeing of working as a doctor: views of the UK
      medical graduates of 1974 and 1977 surveyed in 2014.
AB  - Objective To report on any adverse effects on health and wellbeing of working as
      a doctor, as described by senior doctors. Design Questionnaires sent in 2014 to
      all medical graduates of 1974 and 1977. Participants 3695 UK medical graduates.
      Setting United Kingdom. Main outcome measures Statements about adverse effects
      upon health, wellbeing and career. Results The aggregated response rate from
      contactable doctors was 84.6% (3695/4369). In response to the question 'Do you
      feel that working as a doctor has had any adverse effects on your own health or
      wellbeing?', 44% of doctors answered 'yes'. More GPs (47%) than hospital doctors
      (42%) specified that this was the case. Three-quarters of doctors who answered
      'yes' cited 'stress/work-life balance/workload' as an adverse effect, and 45%
      mentioned illness. In response to the statement 'The NHS of today is a good
      employer when doctors become ill themselves', 28% of doctors agreed, 29% neither
      agreed nor disagreed and 43% disagreed. More women doctors (49%) than men doctors
      (40%) disagreed with this statement. More general practitioners (49%) disagreed
      than hospital doctors (37%). Conclusions Chronic stress and illness, which these
      doctors attributed to their work, were widely reported. Although recent changes
      may have alleviated some of these issues, there are lessons for the present and
      future if the NHS is to ensure that its medical workforce receives the support
      which enables current doctors to enjoy a full and satisfying career and to
      contribute fully to health service provision in the UK. Older doctors, in
      particular, need support to be able to continue successfully in their careers.

PMID- 28504073
TI  - Exploring the relationship between mentoring and doctors' health and wellbeing: a
      narrative review.
AB  - The health and wellbeing of doctors are crucial, both for the individuals
      themselves and their ability to deliver optimum patient care. With increased
      pressures on healthcare, support mechanisms that attend to doctors' health and
      wellbeing may require greater emphasis to safeguard those working in frontline
      services. To inform future developments, this systematic narrative review aimed
      to identify, explore and map empirical and anecdotal evidence indicating the
      relationships between mentoring activities and the health and wellbeing of
      doctors. Twelve databases were searched for publications printed between January
      2006 and January 2016. Articles were included if they involved doctors'
      engagement in mentoring activities and, either health or wellbeing, or the
      benefits, barriers or impact of mentoring. The initial search returned 4669
      papers, after exclusions a full-text analysis of 37 papers was conducted.
      Reference lists and citations of each retrieved paper were also searched.
      Thirteen papers were accepted for review. The Business in the Community model was
      used as a theoretical framework for analysis. Mentoring influenced collegiate
      relationships, networking and aspects of personal wellbeing, such as confidence
      and stress management, and was valued by doctors as a specialist support
      mechanism. This review contributes to the evidence base concerning mentoring and
      doctors' health and wellbeing. However, it highlights that focused research is
      required to explore the relationship between mentoring, and health and wellbeing.

PMID- 28504076
TI  - Firm findings on doctors' wellbeing.

PMID- 28504077
TI  - Routine Shunting During Carotid Endarterectomy in Patients With Acute Watershed
      Stroke.
AB  - AIM: To evaluate the protective role of routine shunting in patients with acute
      watershed stroke (WS) undergoing carotid endarterectomy (CEA). METHODS: A total
      of 138 patients with symptomatic carotid stenosis (SCS) who underwent CEA after
      acute ischemic stroke from March 2008 to March 2015 were included in this study.
      Transient ischemic attacks were excluded. These patients were divided into 2
      groups according to the topographic pattern of the stroke on magnetic resonance
      imaging: group 1, territorial strokes (TS) caused by emboli of carotid origin,
      and group 2, WS caused by a hemodynamic mechanism related to an SCS. Primary end
      points were 30-day mortality and postoperative neurological morbidity. The
      insertion of a Pruitt carotid shunt was performed systematically. RESULTS: Ninety
      (65.2%) patients presented a TS of carotid origin and were included in group 1,
      and 48 (34.8%) of the 138 patients had a WS related to an SCS and were included
      in group 2. The median time between clinical onset of the cerebral ischemic event
      and surgery was 9 days (range: 0-89 days). Postoperative mortality was 0%. Seven
      (5.1%) patients had an aggravation of the neurological status during the
      postoperative period, of whom 2 presented a complete regression of the symptoms
      in less than 1 hour (definitive postoperative neurologic morbidity: 3.6%).
      Postoperative neurologic morbidity rate was significantly higher in the TS group
      (7 of 90; 7.8%) compared to the WS group (0 of 48; P = .04). No other independent
      predictive factor of neurologic morbidity after CEA for an SCS was found.
      CONCLUSIONS: Our results suggest that routine shunting should be considered in
      case of acute WS since it may play a protective role. Further studies are eagerly
      awaited to better define the timing and the best treatment option for both acute
      WS and TS related to an SCS in order to reduce postoperative neurologic
      morbidity.

PMID- 28504078
TI  - A review on therapeutic potentials of Trigonella foenum graecum (fenugreek) and
      its chemical constituents in neurological disorders: Complementary roles to its
      hypolipidemic, hypoglycemic, and antioxidant potential.
AB  - OBJECTIVES: The growing rate of neurological disorders is a major concern in
      today's scenario. Today's research is focusing on therapeutic interventions
      providing benefits in these disorders. Presently, drugs of natural origin have
      gained more interest for the treatment of central nervous system disorders for
      their efficacy and less/ no side effects. This review is emphasizing the cited
      roles of Trigonella foenum graecum (fenugreek) and its constituents in different
      neurological manifestations. METHOD: A review of the literature, relevant to the
      role of fenugreek and its major constituents including saponins and alkaloids in
      different neurological aspects and in delineating the health benefits, was
      conducted. RESULTS: The cited research acknowledged that fenugreek and its
      constituents exert positive influence on neurological health. Few studies have
      reported the beneficial role of fenugreek and its constituents like trigonelline
      in pathological symptoms of Alzheimer's disease. Similarly, other studies
      evidenced the neuroprotective, antidepressant, antianxiety as well as modulatory
      effect on cognitive functions and Parkinson's disease. DISCUSSION: Large
      populations are the sufferers of the neurological disorders, pointing the need
      for investigation of such therapeutic interventions which target and delay the
      underlying pathological hallmarks and exert positive influence on different
      neurological health problems. Hypolipidemic, hypoglycemic, antioxidant, and
      immunomodulatory effects of fenugreek and its constituents with their potential
      role in various neurological disorders were already reported. In future, it would
      be of even greater interest to further develop more effective dosage,
      supplementation period, and to evaluate the therapeutic potentials of fenugreek
      and its constituents in neurological disorders by exploring underlying cellular
      and molecular mechanisms.

PMID- 28504079
TI  - A novel nonsense NBEAL2 gene mutation causing severe bleeding in a patient with
      gray platelet syndrome.
AB  - Gray platelet syndrome (GPS) is a rare, inherited bleeding disorder characterized
      by the defect of platelet alpha-granule. Up to date, these are only four studies
      identifying NBEAL2 gene correlated with GPS. In the current report, we present a
      Chinese GPS patient who had severe bleeding tendency, abnormalities of platelet
      functions, and absence of platelet alpha-granules. Genomic DNA sequencing for the
      patient identified a nonsense mutation (g.27713C>A) of NBEAL2 gene
      (g.NG__031914.1) resulting in a premature protein (p.Glu1726*). In comparison
      with the reported patients, we conclude that homozygotes with nonsense or
      deletion mutation leading to a premature stop codon exhibit more serious bleeding
      problem than those with missense mutations.

PMID- 28504080
TI  - Expected p-values in light of an ROC curve analysis applied to optimal multiple
      testing procedures.
AB  - Many statistical studies report p-values for inferential purposes. In several
      scenarios, the stochastic aspect of p-values is neglected, which may contribute
      to drawing wrong conclusions in real data experiments. The stochastic nature of p
      values makes their use to examine the performance of given testing procedures or
      associations between investigated factors to be difficult. We turn our focus on
      the modern statistical literature to address the expected p-value (EPV) as a
      measure of the performance of decision-making rules. During the course of our
      study, we prove that the EPV can be considered in the context of receiver
      operating characteristic (ROC) curve analysis, a well-established biostatistical
      methodology. The ROC-based framework provides a new and efficient methodology for
      investigating and constructing statistical decision-making procedures, including:
      (1) evaluation and visualization of properties of the testing mechanisms,
      considering, e.g. partial EPVs; (2) developing optimal tests via the minimization
      of EPVs; (3) creation of novel methods for optimally combining multiple test
      statistics. We demonstrate that the proposed EPV-based approach allows us to
      maximize the integrated power of testing algorithms with respect to various
      significance levels. In an application, we use the proposed method to construct
      the optimal test and analyze a myocardial infarction disease dataset. We outline
      the usefulness of the "EPV/ROC" technique for evaluating different decision
      making procedures, their constructions and properties with an eye towards
      practical applications.

PMID- 28504082
TI  - Enhancing the Reproducibility of Research Findings.

PMID- 28504083
TI  - Comment on "Drug survival analysis is not a good method for assessing the safety
      or effectiveness of systemic therapies in psoriasis".

PMID- 28504084
TI  - Dermoscopic Features of Facial Trichilemmoma.

PMID- 28504085
TI  - Buried Sutures to Facilitate the Closure of Facial Defects.

PMID- 28504081
TI  - Dissecting physical structure of calreticulin, an intrinsically disordered Ca2+
      buffering chaperone from endoplasmic reticulum.
AB  - Calreticulin (CALR) is a Ca2+ binding multifunctional protein that mostly resides
      in the endoplasmic reticulum (ER) and plays a number of important roles in
      various physiological and pathological processes. Although the major functions
      ascribed to CALR are controlling the Ca2+ homeostasis in ER and acting as a
      lectin-like ER chaperon for many glycoproteins, this moonlighting protein can be
      found in various cellular compartments where it has many non-ER functions. To
      shed more light on the mechanisms underlying polyfunctionality of this
      moonlighting protein that can be found in different cellular compartments and
      that possesses a wide spectrum of unrelated biological activities, being able to
      interact with Ca2+ (and potentially other metal ions), RNA, oligosaccharides, and
      numerous proteins, we used a set of experimental and computational tools to
      evaluate the intrinsic disorder status of CALR and the role of calcium binding on
      structural properties and conformational stability of the full-length CALR and
      its isolated P- and C-domains.

PMID- 28504086
TI  - Drug-Induced Eruptive Melanocytic Nevi.

PMID- 28504087
TI  - Response to the Comment by Van den Reek et al. on Drug Survival Analysis is not a
      Good Method for Assessing the Safety or Effectiveness of Systemic Therapies in
      Psoriasis.

PMID- 28504088
TI  - Greater Detection of Small Caliber Blood Vessels in Port Wine Stain with X Mode
      Than With Conventional Doppler: A Pilot Study.

PMID- 28504089
TI  - Immunohistochemical expression of interferon-gamma in different types of
      granulomatous lesions associated with bovine paratuberculosis.
AB  - Animals infected with Mycobacterium avium subsp. paratuberculosis (Map) show a
      variety of lesions, from focal forms, seen in subclinical stages to diffuse
      lesions in clinical cases. The purpose of this study was to evaluate the local
      expression of IFN-gamma by immunohistochemistry in relation with the type of
      lesion in naturally Map-infected cows. The number of immunolabelled cells, -the
      majority morphologically consistent with lymphocytes-, was higher in focal and
      diffuse paucibacillary forms than in diffuse multibacillary lesions, where they
      appeared closely related to epithelioid cells. Diffuse multibacillary lesions had
      the lowest numbers, but higher than controls, and positive cells were
      intermingled among the macrophages. The peripheral IFN-gamma production was
      higher in all Map infected cows and a positive correlation was found with the
      number of immunolabelled cells in the intestine. The findings of this study show
      that IFN-gamma would play a role in the development of the different types of
      lesions in paratuberculosis, and also points out the importance of adequate
      sampling of lymphoid tissue containing samples when studying the local immune
      response in which IFN-gamma expression may be involved, especially in cases where
      focal lesions are present.

PMID- 28504090
TI  - Wound healing in cutaneous leishmaniasis: A double edged sword of IL-10 and TGF
      beta.
AB  - Immune responses have a crucial role during the wound healing process in
      cutaneous leishmaniasis (CL). However, there are several paradoxes in immunity
      against CL. On the one hand, regulatory cytokines interleukin (IL)-10 and
      transforming growth factor beta (TGF-beta) increase susceptibility to CL through
      suppression of several proinflammatory cytokines that require for defense against
      CL. On the other hand, these cytokines play a pivotal role in the acceleration of
      wound healing process. This review discusses about the dual role of IL-10 and TGF
      beta during the wound healing process and immunity against CL to offer a new
      insight about wound healing in CL.

PMID- 28504091
TI  - Toll like receptor 4: an important molecule in recognition and induction of
      appropriate immune responses against Chlamydia infection.
AB  - Chlamydia species are obligate intracellular pathogens causing different
      infectious diseases particularly asymptomatic genital infections and are also
      responsible for a wide range of complications. Previous studies showed that there
      are different immune responses to Chlamydia species and their infections are
      limited to some cases. Moreover, Chlamydia species are able to alter immune
      responses through modulating the expression of some immune system related
      molecules including cytokines. Toll like receptors (TLRs) belonge to pathogen
      recognition receptors (PRRs) and play vital roles in recognition of microbes and
      stimulation of appropriate immune responses. Therefore, it appears that TLRs may
      be considered as important sensors for recognition of Chlamydia and promotion of
      immune responses against these bacterial infections. Accordingly, TLR4 detects
      several microbial PAMPs such as bacterial lipopolysacharide (LPS) and
      subsequently activates transcription from pro-inflammatory cytokines in both
      MYD88 and TRIF pathways dependent manner. The purpose of this review is to
      provide the recent data about the status and major roles played by TLR4 in
      Chlamydia species recognition and promotion of immune responses against these
      infections and also the relationship between TLR4 activities and pathogenesis of
      Chlamydia infections.

PMID- 28504092
TI  - Mycoplasma sp. infection in captive Marcgrave's capuchin monkeys (Sapajus
      flavius).
AB  - Three species of hemoplasmas are known to infect monkeys, 'Candidatus Mycoplasma
      kahanei', 'Candidatus Mycoplasma haemomacaque' and 'Candidatus Mycoplasma aoti'.
      Marcgrave's capuchin monkey (Sapajus flavius) is a critically endangered
      neotropical primate species of the Brazilian Atlantic Forest, and thus, sustained
      efforts are needed to protect the health and well-being of these animals. This
      study has aimed to screen 12 captive S. flavius from the State of Paraiba,
      northeastern Brazil, for hemoplasma infection. Packed cell volume (PCV) was
      measured and a pan-hemoplasma PCR protocol performed. A total of 8/12 (66.6%)
      monkeys were positive for the 16S rDNA gene of Mycoplasma sp., showing an
      identity of 99% to Mycoplasma sp. previously detected in Sapajus apella and
      Sapajus sp. monkeys from the Brazilian Amazon. Further studies should be
      conducted in order to elucidate whether this potentially novel Mycoplasma sp. is
      able to cause anemia in Sapajus sp. monkeys from Brazil.

PMID- 28504093
TI  - Genetic characterization of Staphylococcus aureus isolated from nasal samples of
      healthy ewes in Tunisia. High prevalence of CC130 and CC522 lineages.
AB  - Staphylococcus aureus is a versatile bacterium, which can infect or colonize a
      variety of host species. The objective of this study was to characterize S.
      aureus isolates recovered from nasal swabs of 167 healthy ewes sampled from 12
      farms in different areas of Tunisia during the period of 2014-2015. Genetic
      lineages, virulence factors and antibiotic resistance mechanisms were determined
      for recovered isolates. S. aureus was detected in 45 out of 167 tested samples
      (26.9%). All isolates were methicillin-susceptible (MSSA) and the majority of
      them were susceptible to tested antibiotics with few exceptions (% of
      resistance): penicillin (8.8), ciprofloxacin (4.4), and tobramycin or
      tetracycline (2.2, each). Twelve different spa types were detected (t15098,
      t15099, t1773, t3576, t1534, t5428, t3750, t5970 t254, t2883, t127 and t933), two
      of them were new (t15098 and t15099). S. aureus isolates were ascribed to agrI
      (n=23), agrII (n=1) and agrIII (n=20), and one was non-typeable. According to the
      sequence-type (ST) determined and/or the spa-type detected, the 45S. aureus
      isolates were assigned to six clonal complexes, with CC522 (44.4%) and CC130
      (37.7%) being the most common lineages. Twenty-one (46.6%) and two (4.2%)
      isolates harbored the tst and eta genes encoding TSST-1 and ETA, respectively. In
      conclusion, nares of healthy ewes could be a reservoir of MSSA CC522 and CC130,
      lineages associated with TSST-1 and ETA that might represent a risk to human
      health.

PMID- 28504094
TI  - Antimicrobial activity of red-tailed phascogale (Phascogale calura) serum.
AB  - Antimicrobial substances in serum include circulating complement proteins and
      acute phase proteins (APPs). We identified gene sequences for APPs, haptoglobin
      (Hp), C-reactive protein (CRP) and serum amyloid A (SAA) in marsupial genomes. Hp
      and SAA levels were measured in red-tailed phascogale (Phascogale calura) sera
      using commercially available assays. Hp levels were higher in males than females,
      while SAA levels suggest the phascogales used in this study were healthy. Serum
      was co-cultured with four bacterial species. Bacterial growth was inhibited after
      incubation at 37 degrees C, however effectiveness differed with bacteria and
      incubation time. The least amount of bacterial growth was noticed after
      introduction to K. pneumoniae, and most when introduced to P. aeruginosa. Despite
      marsupials not having mature immune tissues at birth, and unable to mount
      specific immune responses, this study suggests other immune strategies, such as
      APPs in serum likely aid marsupials in their defence against pathogens.

PMID- 28504095
TI  - Characterization of porcine Trueperella pyogenes by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), molecular
      typing and antimicrobial susceptibility profiling in Sao Paulo State.
AB  - Trueperella pyogenes can be found as a commensal or pathogenic bacterium among
      animals causing a variety of pyogenic infections in several species. The agent
      appears to act primarily as an opportunistic pathogen but may disseminate and
      produce metastatic abscesses accompanied or not by mastitis, metritis or
      pneumonia. In this study, 30 porcine T. pyogenes strains were identified by MALDI
      TOF MS and 16S rRNA sequencing and further evaluated in relation to their
      resistance and genetic profiles through broth microdilution and single enzyme
      AFLP. All strains were susceptible to beta-lactams, florfenicol, gentamicin,
      spectinomycin and tiamulin. The highest resistance rates were observed for
      sulfonamides, tetracyclines and clindamycin. All isolates could be characterized
      by SE-AFLP presenting more than 80% of similarity, despite their distinct
      origins. Four genotypes were detected with the segregation of T. pyogenes ATCC
      19411 from Brazilian T. pyogenes strains. No correlation between genotypes and
      isolates origins and susceptibility profile was observed.

PMID- 28504096
TI  - Multiple clones and low antimicrobial resistance rates for Salmonella enterica
      serovar Infantis populations in Greece.
AB  - All the Salmonella enterica ser. Infantis strains isolated under official control
      programs in Greece during a four year period were studied, 23 of human origin, 16
      from food animals and one from food. Molecular analyses (PFGE) in combination
      with antimicrobial susceptibility testing were used to study whether the
      occurrence S. Infantis in Greece resulted from different biotypes or a successful
      spread of one clone. Low rates of antimicrobial resistance were observed, except
      for streptomycin among human isolates (48%), indicating that selective pressure
      due to consumption of antimicrobials has not resulted the spread of dominant
      clones. Pulsed Field Gel Electrophoresis revealed 31 XbaI distinct pulsotypes
      among the 40 strains with 60% overall similarity reflecting diversity. Four main
      clusters were constructed, using an 85% cut off value, clusters A, B, C and D
      consisting of 14, 6, 8 and 8 isolates respectively. Point source of transmission
      was not hypothesized as multiple reservoirs of the serovar seem to be present in
      Greece during the study period.

PMID- 28504097
TI  - Humoral immune responses of experimentally Eimeria ninakholyakimovae-infected
      goat kids.
AB  - Although cellular immune reactions seem to be crucial for protective immune
      responses in Eimeria spp. infections, there are also evidences on an active
      involvement of the humoral counterpart. In the present study, we have analyzed
      the humoral response of goat kids subjected to primary and challenge infections
      with Eimeria ninakholyakimovae. Specific levels of IgG and IgM in serum samples
      and IgA in the ileal mucus were estimated. In infected kids, significantly
      increased levels of IgG were observed from 3 weeks post infection onwards in
      addition to an enhancement of specific IgM and secretory IgA levels. A wide range
      of peptides of sporulated oocyst antigen (SOA) was recognized by specific IgG as
      determined by immunoblotting. However, no correlations were found between
      immunoglobulin levels and OPG counts after challenge infection. Overall, these
      data indicate a significant specific humoral response of E. ninakohlyakimovae
      infected goat kids that does not seem to convey immunoprotection. Further studies
      should be addressed to clarify if the lack of correlation might be associated to
      the type of antigen used for the immunoenzimatic assays, the age of the animals
      or other factors.

PMID- 28504098
TI  - First molecular detection of Dirofilaria immitis (Spirurida: Onchocercidae)
      infection in dogs from Northern Algeria.
AB  - Dirofilaria immitis and Dirofilaria repens are mosquito-borne filarioid nematodes
      that affect dogs and other domestic and wild carnivores, causing heartworm
      disease and subcutaneous dirofilariosis, respectively. In Algeria, the data about
      the epidemiology of these infections is largely unknown. The present study was
      designed to establish the occurrence of D. immitis and D. repens in dogs in
      Algeria using molecular tools. In 2014 and 2015, a total of 209 dogs over one
      year of age of different breed and sex, living in Northern Algeria, were examined
      and blood samples were collected from each dog. The presence of D. immitis and D.
      repens in these samples was detected by real-time PCR followed by standard PCR
      and sequencing. Overall, the blood of 209 dogs from two departments was collected
      and only 3 (1.4%) of the blood samples were found positive for D. immitis DNA.
      Sequencing of the corresponding amplicon displayed a 99.8% identity to D.
      immitis, confirming the presence of this mosquito-borne nematode in Algeria.
      Furthermore, all tested samples were negative for D. repens.

PMID- 28504099
TI  - Zoonotic intestinal parasites and vector-borne pathogens in Italian shelter and
      kennel dogs.
AB  - This study investigated the presence of zoonotic parasites and vector-borne
      pathogens in dogs housed in kennels and shelters from four sites of Italy. A
      total of 150 adoptable dogs was examined with different microscopic, serological
      and molecular methods. Overall 129 dogs (86%) were positive for one or more
      parasites and/or pathogens transmitted by ectoparasites. Forty-eight (32%) were
      positive for one infection, while 81 (54%) for more than one pathogen. The most
      common zoonotic helminths recorded were hookworms, roundworms and Capillaria
      aerophila, followed by mosquito-borne Dirofilaria spp. and Dipylidium caninum.
      One hundred and thirteen (77.9%), 6 (4.1%) and 2 (1.4%) dogs were positive for
      Rickettsia spp., Leishmania infantum and Anaplasma spp., respectively. The
      results show that dogs living in rescue facilities from the studied areas may be
      infected by many zoonotic internal parasites and vector-borne pathogens, and that
      control measures should be implemented.

PMID- 28504101
TI  - Prepublication and clinical practice: challenges ahead.

PMID- 28504100
TI  - Ectonucleotidase and adenosine deaminase as inflammatory marker in dairy cows
      naturally infected by Dictyocaulus viviparus.
AB  - The aim of this study was to evaluate the influence of dictyocaulosis (mild or
      severe) on enzymes of NTPDase, 5'-nucleotidase, and adenosine deaminase (ADA) of
      dairy cows naturally infected by Dictyocaulus viviparus. Blood and faeces were
      collected from 22 dairy cows of the same farm to evaluate NTPDase (ATP and ADP
      substrate), 5'-nucleotidase, and ADA activities on days 0 (pre-treatment) and 10
      (post-treatment). Seric activities of NTPDase (ATP substrate), 5'-nucleotidase,
      and ADA were lower (P<0.05) in D. viviparus infected animals compared to
      uninfected cows. The number of D. viviparus larvae per gram of faeces varied
      among the animals, and they showed different degrees of severity according to
      respiratory clinical signs of the disease (cough and nasal discharge). Later,
      these cows were divided into two groups: those with mild (n=10) and severe (n=12)
      disease. Cows with severe disease showed higher NTPDase activity (ATP substrate)
      than those with mild disease (P<=0.05). The opposite occurred with NTPDase (ADP
      substrate), 5'-nucleotidase, and ADA in cows with severe disease, that is, the
      enzymatic activity of these seric enzymes significantly decreased (P<=0.05)
      compared to animals with mild disease. Infected animals showed reduced NTPDase
      activity (ATP and ADP substrate) after treatment. No enzymatic changes were
      observed for 5'-nucleotidase, and ADA pre- and post-treatment (P>0.05). Based on
      these results, we conclude that dictyocaulosis alters NTPDase, 5'-nucleotidase,
      and ADA activities of cow naturally infected by the parasite, in consequence the
      enzymes act as inflammatory markers.

PMID- 28504102
TI  - The neurodegenerative prodrome in multiple sclerosis.

PMID- 28504103
TI  - Detection of neurodegenerative disease using olfaction.

PMID- 28504104
TI  - The multiple faces of artwork diagnoses.

PMID- 28504105
TI  - The multiple faces of artwork diagnoses.

PMID- 28504106
TI  - The multiple faces of artwork diagnoses.

PMID- 28504107
TI  - Jorge Sepulcre.

PMID- 28504108
TI  - Tuberculous meningitis and hydrocephalus in Filippino de' Medici.

PMID- 28504109
TI  - Severe traumatic brain injury: targeted management in the intensive care unit.
AB  - Severe traumatic brain injury (TBI) is currently managed in the intensive care
      unit with a combined medical-surgical approach. Treatment aims to prevent
      additional brain damage and to optimise conditions for brain recovery. TBI is
      typically considered and treated as one pathological entity, although in fact it
      is a syndrome comprising a range of lesions that can require different therapies
      and physiological goals. Owing to advances in monitoring and imaging, there is
      now the potential to identify specific mechanisms of brain damage and to better
      target treatment to individuals or subsets of patients. Targeted treatment is
      especially relevant for elderly people-who now represent an increasing proportion
      of patients with TBI-as preinjury comorbidities and their therapies demand
      tailored management strategies. Progress in monitoring and in understanding
      pathophysiological mechanisms of TBI could change current management in the
      intensive care unit, enabling targeted interventions that could ultimately
      improve outcomes.

PMID- 28504111
TI  - Olfactory dysfunction in neurodegenerative diseases: is there a common
      pathological substrate?
AB  - In patients with neurodegenerative diseases, there is a spectrum of smell
      dysfunction ranging from severe loss, as seen in Alzheimer's disease and
      Parkinson's disease, to relatively little loss, as seen in progressive
      supranuclear palsy. Given the ubiquitous but varying degrees of olfactory
      dysfunction among such diseases, it is conceivable that differential disruption
      of a common primordial neuropathological substrate causes these differences in
      olfactory function. For example, the amount of damage to forebrain
      neurotransmitter and neuromodulator circuits, most notably those involving
      cholinergic transmission, appears to be correlated with quantitative smell test
      scores across a wide range of neurodegenerative diseases. Thus, a key question is
      whether damage to such a substrate is the basis for the perceptual differences in
      olfaction or whether disease-specific or other entities, such as respiratory
      infections or pollution, are responsible. In light of the early preclinical onset
      of smell deficits in many neurodegenerative diseases, the answer to this question
      might provide crucial insight into the cause of disease pathology at its earliest
      stages of development.

PMID- 28504110
TI  - Neurological consequences of obesity.
AB  - The high prevalence of obesity is associated with an enormous medical, social,
      and economic burden. The metabolic dysfunction, dyslipidaemia, and inflammation
      caused by obesity contribute to the development of a wide variety of disorders
      and effects on the nervous system. In the CNS, mild cognitive impairment can be
      attributed to obesity-induced alterations in hippocampal structure and function
      in some patients. Likewise, compromised hypothalamic function and subsequent
      defects in maintaining whole-body energy balance might be early events that
      contribute to weight gain and obesity development. In the peripheral nervous
      system, obesity-driven alterations in the autonomic nervous system prompt
      imbalances in sympathetic-parasympathetic activity, while alterations in the
      sensory-somatic nervous system underlie peripheral polyneuropathy, a common
      complication of diabetes. Pharmacotherapy and bariatric surgery are promising
      interventions for people with obesity that can improve neurological function.
      However, lifestyle interventions via dietary changes and exercise are the
      preferred approach to combat obesity and reduce its associated health risks.

PMID- 28504112
TI  - Potential impact of a volume pledge on spatial access: A population-level
      analysis of patients undergoing pancreatectomy.
AB  - BACKGROUND: A minimum-volume policy restricting hospitals not meeting the
      threshold from performing complex operation may increase travel burden and
      decrease spatial access to operation. We aim to identify vulnerable populations
      that would be sensitive to an added travel burden. METHODS: We performed a
      retrospective analysis of the database of the California Office of Statewide
      Health Planning and Development for patients undergoing pancreatectomy from 2005
      to 2014. Number of hospitals bypassed was used as a metric for travel. Patients
      bypassing fewer hospitals were deemed to be more sensitive to an added travel
      burden. RESULTS: There were 13,374 patients who underwent a pancreatectomy, of
      whom 2,368 (17.7%) were nonbypassers. On unadjusted analysis, patients >80 year
      old travelled less than their younger counterparts, bypassing a mean of 10.9 +/-
      9.5 hospitals compared with 14.2 +/- 21.3 hospitals bypassed by the 35-49 year
      old age group (P < .001). Racial minorities travelled less when compared with non
      Hispanic whites (P < .001). Patients identifying their payer status as self-pay
      (8.9 +/- 15.6 hospitals bypassed) and Medicaid (10.1 +/- 17.2 hospitals bypassed)
      also travelled less when compared with patients with private insurance (13.8 +/-
      20.4 hospitals bypassed, P < .001). On multivariate analysis, advanced age,
      racial minority, and patients with self-pay or Medicaid payer status were
      associated independently with increased sensitivity to an added travel burden.
      CONCLUSION: In patients undergoing pancreatectomy, the elderly, racial
      minorities, and patients with self-pay or Medicaid payer status were associated
      with an increased sensitivity to an added travel burden. This vulnerable cohort
      may be affected disproportionately by a minimum-volume policy.

PMID- 28504113
TI  - Prognosis of spontaneous coronary artery dissection treated by percutaneous
      coronary intervention with optical coherence tomography.
AB  - BACKGROUND: Although about half of patients with spontaneous coronary artery
      dissection (SCAD) face ongoing necrosis, conservative therapy is recommended due
      to a high complication rate in angiography-guided percutaneous coronary
      intervention (PCI). The aim of this study was to investigate clinical outcomes of
      SCAD treated by optical coherence tomography (OCT)-guided PCI. METHODS: This
      study consisted of consecutive 306 patients with acute coronary syndrome (ACS)
      who underwent OCT-guided PCI. Based on the culprit lesion morphology by OCT,
      patients were assigned to four groups: a SCAD group, a plaque rupture (PR) group,
      a calcified nodule (CN) group, and an undetermined etiology (UE) group.
      Successful PCI was defined as thrombolysis in myocardial infarction flow grade 3
      in final angiography without any complications. Primary endpoint was defined as
      occurrence rate of major adverse cardiac events (MACE) including cardiac death,
      myocardial infarction, and unstable angina pectoris. RESULTS: OCT revealed 12
      SCADs, 149 PRs, 16 CNs, and 129 UEs, respectively. No significant difference was
      observed in the success rate of PCI (SCAD 91.7%, PR 85.2%, CN 81.2%, UE 86.8%,
      p=0.88), while wire repositioning was needed in 2 SCAD cases (p<0.01). The mean
      follow-up periods were 17.1+/-13.3 months. No significant difference was observed
      in MACE among the groups (p=0.56). CONCLUSIONS: The clinical outcomes of OCT
      guided PCI for SCAD were favorable, as well as those for other ACS etiologies.
      OCT-guided PCI could become a therapeutic option for SCAD compromised with
      ongoing necrosis.

PMID- 28504114
TI  - A shortened tamoxifen induction scheme to induce CreER recombinase without side
      effects on the male mouse skeleton.
AB  - The selective estrogen receptor modulator tamoxifen exerts estrogen agonistic or
      antagonistic actions on several tissues, including bone. The off-target effects
      of tamoxifen are one of the most widely recognized pitfalls of tamoxifen
      inducible Cre recombinases (CreERs), potentially confounding the phenotypic
      findings. Still, the validation of tamoxifen induction schemes that minimize the
      side effects of the drug has not been addressed. Here, we compared the side
      effects on the skeleton and other androgen-responsive targets of a shortened
      tamoxifen regimen (2 doses of 190 mg/kg body weight by oral gavage) to a standard
      protocol (4 doses) and determined their efficiency in inducing CreER-mediated
      gene deletion. In addition, both a vehicle- and a 10-dose group, which served as
      a positive control for tamoxifen side effects, were also included. For this
      purpose, we generated male mice with a floxed androgen receptor (AR) and a neuron
      specifically expressed CreER. Treatment with two doses of tamoxifen was the only
      regimen that did not diminish androgenic bioactivity, as assessed by both seminal
      vesicles and levator ani/bulbocavernosus muscle weights and serum testosterone
      concentrations. Similarly, trabecular and cortical femoral bone structure were
      dramatically altered by both the standard and high-dose protocols but not by the
      shortened version. Serum osteocalcin and bone-gene expression analyses confirmed
      the absence of effects on bone by 2 doses of tamoxifen. This protocol decreased
      AR mRNA levels efficiently and specifically in the nervous system. Thus, we
      optimized a protocol for tamoxifen-induced CreER gene deletion in mice without
      off-target effects on bone and male reproductive organs.

PMID- 28504115
TI  - Protocatechuic acid inhibits hepatitis B virus replication by activating ERK1/2
      pathway and down-regulating HNF4alpha and HNF1alpha in vitro.
AB  - AIMS: Protocatechuic acid (PCA) is a phenolic compound found in many antiviral
      Chinese herbal medicines. HNF4alpha and HNF1alpha, the members of hepatocyte
      nuclear factor (HNF) family, play an important regulatory role in the gene
      transcription of hepatitis B virus (HBV). Previous studies found that PCA
      inhibited HBV antigen secretion and HBV DNA replication in HepG2.2.15 cells, but
      its anti-HBV mechanism has not been fully understood. We aim to illustrate the
      anti-HBV mechanism of PCA. MATERIALS AND METHODS: MTT was used to estimate
      cytotoxicity. The content of HBsAg or HBeAg was detected using an enzyme-linked
      immunosorbent assay kit. HBV DNA in cell-free culture media was detected by PCR
      kit. HNF1alpha and HNF4alpha mRNA expression was detected by real-time PCR.
      HNF1alpha, HNF4alpha and ERK1/2 protein expression was detected by western
      blotting and HBV promoter activity was tested by luciferase reporter assay. KEY
      FINDINGS: Our results demonstrated that PCA inhibited the gene transcription and
      protein translation of HNF1alpha and HNF4alpha in Huh7 and HepG2.2.15 cells, as
      well as the promoter activities of HBV X and preS1 in Huh7 cells transfected with
      the luciferase reporter plasmid of HBV promoter. Further study suggested that PCA
      induced the phosphorylation of extracellular-signal-related kinase (ERK) 1/2, and
      thereby inhibited HNF4alpha and HNF1alpha expression in HepG2.2.15 cells to exert
      its antiviral activity. SIGNIFICANCE: To our knowledge, this study is the first
      to reveal the anti-HBV mechanism of PCA. Our results demonstrate that PCA
      inhibits HBV replication by activating ERK1/2 pathway and subsequently down
      regulating HNF4alpha and HNF1alpha in HepG2.2.15 cells.

PMID- 28504116
TI  - Exercise reverses pain-related weight asymmetry and differentially modulates
      trabecular bone microarchitecture in a rat model of osteoarthritis.
AB  - : There is great interest in developing and utilizing non-pharmacological/non
      invasive forms of therapy for osteoarthritis (OA) pain including exercise and
      other physical fitness regimens. AIMS: The present experiments determined the
      effects of prior wheel running on OA-induced weight asymmetry and trabecular bone
      microarchitecture. MAIN METHODS: Wheel running included 7 or 21days of prior
      voluntary access to wheels followed by OA induction, followed by 21days post-OA
      access to wheels. OA was induced with monosodium iodoacetate (MIA), and weight
      asymmetry was measured using a hind limb weight bearing apparatus. Bone
      microarchitecture was characterized using ex vivo MUCT. KEY FINDINGS: Relative to
      saline controls, MIA (3.2mg/25MUl) produced significant weight asymmetry measured
      on post-days (PDs) 3, 7, 14, 21 in sedentary rats. Seven days of prior running
      failed to alter MIA-induced weight asymmetry. In contrast, 21days of prior
      running resulted in complete reversal of MIA-induced weight asymmetry on all days
      tested. As a comparator, the opioid agonist morphine (3.2-10mg/kg) dose
      dependently reversed weight asymmetry on PDs 3, 7, 14, but was ineffective in
      later-stage (PD 21) OA. In runners, Cohen's d (effect sizes) for OA vs. controls
      indicated large increases in bone volume fraction, trabecular number, trabecular
      thickness, and connective density in lateral compartment, and large decreases in
      the same parameters in medial compartment. In contrast, effect sizes were small
      to moderate for sedentary OA vs. CONTROLS:  SIGNIFICANCE: Results indicate that
      voluntary exercise may protect against OA pain, the effect varies as a function
      of prior exercise duration, and is associated with distinct trabecular bone
      modifications.

PMID- 28504118
TI  - Direct evidence of central nervous system axonal damage in patients with
      postoperative delirium: A preliminary study of pNF-H as a promising serum
      biomarker.
AB  - INTRODUCTION: Approximately 50-80% patients experience postoperative delirium, an
      acute cognitive dysfunction associated with prolonged hospitalization, increased
      mortality, excess healthcare costs, and persistent cognitive impairment.
      Elucidation of the mechanism of delirium and associated diagnostic and
      therapeutic measures are urgently required. Here we investigated the role of
      phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in
      axons, as a predictive maker of postoperative delirium. MATERIAL AND METHODS:
      Twenty-three patients who underwent surgery for abdominal cancer were screened
      for postoperative delirium, and they were assessed for its severity using the
      memorial delirium assessment scale (MDAS) at and 48h after delirium onset. Serum
      pNF-H levels were also measured at both time points. The patients were divided
      into two groups according to the presence or absence of pNF-H. Clinical variables
      were compared between groups using the Mann-Whitney U test, and the relationship
      between pNF-H levels and delirium severity was analyzed using the exponential
      curve fitting. RESULTS: Fifteen of the 23 (65.2%) patients tested positive for
      pNF-H, and these patients exhibited significantly higher MDAS scores compared
      with the pNF-H-negative patients only at the onset of delirium. Although the MDAS
      score significantly improved over time in the positive group, pNF-H positivity
      persisted. There was a correlation between the maximum pNF-H level and maximum
      MDAS score (R2=0.31, p=0.013). CONCLUSIONS: More severe postoperative delirium
      was directly related to higher serum pNF-H levels, suggesting the potential
      application of pNF-H as a quantitative biomarker of neural damage in
      postoperative delirium.

PMID- 28504117
TI  - Surround Integration Organizes a Spatial Map during Active Sensation.
AB  - During active sensation, sensors scan space in order to generate a representation
      of the outside world. However, since spatial coding in sensory systems is
      typically addressed by measuring receptive fields in a fixed, sensor-based
      coordinate frame, the cortical representation of scanned space is poorly
      understood. To address this question, we probed spatial coding in the rodent
      whisker system using a combination of two-photon imaging and electrophysiology
      during active touch. We found that surround whiskers powerfully transform the
      cortical representation of scanned space. On the single-neuron level, surround
      input profoundly alters response amplitude and modulates spatial preference in
      the cortex. On the population level, surround input organizes the spatial
      preference of neurons into a continuous map of the space swept out by the
      whiskers. These data demonstrate how spatial summation over a moving sensor array
      is critical to generating population codes of sensory space.

PMID- 28504119
TI  - The ratio of 1/3 linoleic acid to alpha linolenic acid is optimal for
      oligodendrogenesis of embryonic neural stem cells.
AB  - During neural development, embryonic neural stem cells (eNSCs) differentiate
      toward glial, oligodendrocytic, and neuronal cells. Dysregulation of
      polyunsaturated fatty acids (PUFAs) induce a wide range of neurological and
      developmental disorders. In this study, we investigated the effect of various
      concentrations and ratios of linoleic acid (LA) and alpha linolenic acid (ALA),
      which belong respectively to omega-6 and omega-3 PUFAs, on the proliferation and
      differentiation of eNSCs.Results showed that low (25 and 50MUM) or high (100 and
      200MUM) concentrations of ALA, but not LA, and the ratio of 1:3 of LA/ALA
      significantly increased neurospheres size, frequency and cell numbers, in
      comparison to controls. Moreover, low or high concentrations of ALA, but not LA,
      and different ratios of LA/ALA resulted in a significant increase in mRNA
      expression levels of Notch1, Hes1 and Ki-67, and the differentiation of eNSCs
      toward astrocytes (GFAP) and oligodendrocytes (MBP), but not neurons (beta-III
      Tubulin), with the highest increase being for LA/ALA ratio of 1:3, in comparison
      to controls. These results demonstrate the importance of higher concentrations of
      ALA in enhancing proliferation and differentiation of eNSCs, which could be used
      in diet to help preventing neurodevelopmental syndromes, cognitive decline during
      aging, and various psychiatric disorders.

PMID- 28504120
TI  - Mismatch negativity (MMN) to speech sounds is modulated systematically by manual
      grip execution.
AB  - Manual actions and speech are connected: for example, grip execution can
      influence simultaneous vocalizations and vice versa. Our previous studies show
      that the consonant [k] is associated with the power grip and the consonant [t]
      with the precision grip. Here we studied whether the interaction between speech
      sounds and grips could operate already at a pre-attentive stage of auditory
      processing, reflected by the mismatch-negativity (MMN) component of the event
      related potential (ERP). Participants executed power and precision grips
      according to visual cues while listening to syllable sequences consisting of [ke]
      and [te] utterances. The grips modulated the MMN amplitudes to these syllables in
      a systematic manner so that when the deviant was [ke], the MMN response was
      larger with a precision grip than with a power grip. There was a converse trend
      when the deviant was [te]. These results suggest that manual gestures and speech
      can interact already at a pre-attentive processing level of auditory perception,
      and show, for the first time that manual actions can systematically modulate the
      MMN.

PMID- 28504121
TI  - Corticospinal excitability during the processing of handwritten and typed words
      and non-words.
AB  - A number of studies have suggested that perception of actions is accompanied by
      motor simulation of those actions. To further explore this proposal, we applied
      Transcranial magnetic stimulation (TMS) to the left primary motor cortex during
      the observation of handwritten and typed language stimuli, including words and
      non-word consonant clusters. We recorded motor-evoked potentials (MEPs) from the
      right first dorsal interosseous (FDI) muscle to measure cortico-spinal
      excitability during written text perception. We observed a facilitation in MEPs
      for handwritten stimuli, regardless of whether the stimuli were words or non
      words, suggesting potential motor simulation during observation. We did not
      observe a similar facilitation for the typed stimuli, suggesting that motor
      simulation was not occurring during observation of typed text. By demonstrating
      potential simulation of written language text during observation, these findings
      add to a growing literature suggesting that the motor system plays a strong role
      in the perception of written language.

PMID- 28504122
TI  - GABAB receptors and pain.
AB  - Over the past three decades the research on GABAB receptor biology and
      pharmacology in pain processing has been a fascinating experience. Norman
      Bowery's fundamental discovery of the existence of the GABAB receptor has led the
      way to the definition of GABAB molecular mechanisms; patterns of receptor
      expression in the peripheral and central nervous system; GABAB modulatory
      functions within the pain pathways. We are now harnessing this acquired knowledge
      to develop innovative approaches to the therapeutic management of chronic pain
      through allosteric modulation of the GABAB. Norman's legacy would be ultimately
      fulfilled by the development of novel analgesics that activate the GABAB
      receptor. This article is part of the "Special Issue Dedicated to Norman G.
      Bowery".

PMID- 28504123
TI  - Erythropoietin and small molecule agonists of the tissue-protective
      erythropoietin receptor increase FXN expression in neuronal cells in vitro and in
      Fxn-deficient KIKO mice in vivo.
AB  - Friedreich's ataxia (FA) is a progressive neurodegenerative disease caused by
      reduced levels of the mitochondrial protein frataxin (FXN). Recombinant human
      erythropoietin (rhEPO) increased FXN protein in vitro and in early clinical
      studies, while no published reports evaluate rhEPO in animal models of FA. STS
      E412 and STS-E424 are novel small molecule agonists of the tissue-protective, but
      not the erythropoietic EPO receptor. We find that rhEPO, STS-E412 and STS-E424
      increase FXN expression in vitro and in vivo. RhEPO, STS-E412 and STS-E424
      increase FXN by up to 2-fold in primary human cortical cells and in retinoic-acid
      differentiated murine P19 cells. In primary human cortical cells, the increase in
      FXN protein was accompanied by an increase in FXN mRNA, detectable within 4 h.
      RhEPO and low nanomolar concentrations of STS-E412 and STS-E424 also increase FXN
      in normal and FA patient-derived PBMC by 20%-40% within 24 h, an effect that was
      comparable to that by HDAC inhibitor 4b. In vivo, STS-E412 increased Fxn mRNA and
      protein in wild-type C57BL6/j mice. RhEPO, STS-E412, and STS-E424 increase FXN
      expression in the heart of FXN-deficient KIKO mice. In contrast, FXN expression
      in the brains of KIKO mice increased following treatment with STS-E412 and STS
      E424, but not following treatment with rhEPO. Unexpectedly, rhEPO-treated KIKO
      mice developed severe splenomegaly, while no splenomegaly was observed in STS
      E412- or STS-E424-treated mice. RhEPO, STS-E412 and STS-E424 upregulate FXN
      expression in vitro at equal efficacy, however, the effects of the small
      molecules on FXN expression in the CNS are superior to rhEPO in vivo.

PMID- 28504124
TI  - Structural characterization and rheological properties of a gel-like beta-d
      glucan from Pholiota nameko.
AB  - A crude fraction (SCW) was extracted with cold water from Pholiota nameko and
      showed mannose (24.1%), galactose (44.9%) and glucose (31%). Purification
      procedures resulted in a polysaccharide fraction (bG-PN), that showed only
      glucose. NMR and methylation analyses of bG-PN indicated a beta-d-glucan-(1->3)
      linked, substituted at O-6 by beta-d-Glcp or (1->6)-linked beta-d-Glcp side
      chains. Rheological studies of crude and purified fractions at the same
      concentration showed similar shear-thinning behavior and gel-like structure which
      indicates no need to isolate the polymer to achieve some desirable rheological
      properties. SCW (at 1% and 2%) and bG-PN (at 2%) presented thermal stability
      during heating and cooling, suggesting that the physical structure of gels (SCW
      and bG-PN at 2%) and viscoelastic fluid (SCW at 1%) formed were not altered in
      the tested temperature range. Our results suggest that P. nameko beta-d-glucans
      can be applied in different food preparations as thickener or gelling agents
      modifying their rheological properties.

PMID- 28504125
TI  - Preparation of chitosan-TiO2 composite film with efficient antimicrobial
      activities under visible light for food packaging applications.
AB  - By incorporation of TiO2 nano-powder in chitosan, a chitosan-TiO2 composite film
      was prepared with efficient antimicrobial activity against food-borne pathogenic
      microbes and expected to be a promising food packaging material. Scanning
      electron microscopy analysis showed that the TiO2 nano-powder was successfully
      and uniformly dispersed into the chitosan matrix. TiO2 addition led to enhanced
      hydrophilicity, to better mechanical properties, and to decreased light
      transmittance in visible light region of the composite film. The chitosan-TiO2
      film possessed efficient antimicrobial activity against four tested strains, i.e.
      Escherichia coli, Staphylococcus aureus, Candida albicans, and Aspergillus niger
      with 100% sterilization in 12h. It moreover provoked the leakage of cellular
      substances through damaged membrane. The prepared chitosan-TiO2 film was tested
      for packaging red grapes to prevent microbial infection and extend their shelf
      life. Results were positive, stressing the potential of the novel bio-nano
      composite film for food packaging applications.

PMID- 28504126
TI  - Chemical modification of nanocellulose with canola oil fatty acid methyl ester.
AB  - Cellulose nanocrystals (CNCs), produced from dissolving wood pulp, were
      chemically functionalized by transesterification with canola oil fatty acid
      methyl ester (CME). CME performs as both the reaction reagent and solvent.
      Transesterified CNC (CNCFE) was characterized for their chemical structure,
      morphology, crystalline structure, thermal stability, and hydrophobicity.
      Analysis by Fourier transform infrared (FTIR) and FT-Raman spectroscopies showed
      that the long chain hydrocarbon structure was successfully grafted onto CNC
      surfaces. After transesterification the crystal size and crystallinity of
      nanocrystals were not changed as determined by Raman spectroscopy and wide angle
      X-ray diffraction (XRD). CNCFE showed higher thermal stability and smaller
      particle size than unmodified CNCs. Water contact angle measurement indicated the
      CNCFE surface has significantly higher hydrophobicity than unmodified CNCs. The
      transesterified CNCs could be potentially used as hydrophobic coatings and
      reinforcing agents to hydrophobic polymer for nanocomposites.

PMID- 28504127
TI  - Complexation of kappa-carrageenan with gelatin in the aqueous phase analysed by
      1H NMR kinetics and relaxation.
AB  - The 1H NMR spectroscopy is used to study the kinetics of gelation in the aqueous
      mixtures of kappa-carrageenan with gelatin. The time dependence of NMR signals
      intensities shows that the kinetics of gel formation consists of classical 'fast'
      (rate constant k~6h-1) and 'slow' (k~1h-1) periods, corresponding to a coil
      >helix transition and subsequent aggregation of helices. Upon increase of the
      kappa-carrageenan/gelatin (w/w) ratio Z the rate of the fast process slows down
      by a factor of 1.6-2.4. Further analysis was done by studying the dependence of
      spin-spin relaxation times of protons of gelatin on Z in the aqueous phase. A
      qualitative scheme describing hydrogel formation in the complex solution is
      given. It is hypothesized that at higher concentration of PECs the hydrogel
      structure network is stabilized by three types of nodes: triple helices of
      gelatin and intra-/inter-molecular double helices of kappa-carrageenan.

PMID- 28504128
TI  - Combined emulsifying capacity of polysaccharide particles of different size and
      shape.
AB  - The aim of this study is to understand mixed systems of two types of particles
      with different size and shape, quinoa starch granules (NQ) and cellulose
      nanocrystals (CNC), to stabilize oil-in-water (O/W) emulsions. This study
      considers the extent of Pickering stabilization with respect to which particle
      type dominates at droplet interfaces and how stability is affected by the
      addition of one particle type to already formed emulsions, or combining both,
      simultaneously. Results demonstrate that the order of addition has an influence
      allowing to predominantly have NQ particles at the interface when both types are
      added simultaneously. However when CNC is added first, both types are responsible
      for emulsion stabilization leading to a system with an intermediate droplet size
      yet with a higher stability compared to single particle formulations. A dual
      stabilization mechanism is observed, large particles prevent coalescence and
      small particles regulate the curvature of the interface and govern the droplet
      size.

PMID- 28504129
TI  - Tunicate cellulose nanocrystals reinforced nanocomposite hydrogels comprised by
      hybrid cross-linked networks.
AB  - Cellulose nanocrystals are considered as promising biomass nanofillers for
      polymeric hydrogels, but poor interface compatibility between cellulose
      nanocrystals and hydrogel matrix usually reduces their reinforcement effect.
      Here, we reported a novel interface compatible nanocomposite hydrogel prepared by
      introducing quaternized tunicate cellulose nanocrystals (Q-TCNCs) into chemically
      cross-linked poly (acrylic acid) (PAA) networks. Q-TCNCs acted as both
      nanofillers and physical cross-linkers in the PAA networks, and the electrostatic
      interaction between the positive charges of Q-TCNCs and negative charges of PAA
      chains improved their interface compatibility. The nanocomposite hydrogels
      exhibited controllable swelling ratio and pH-sensitive swelling behaviors. The
      mechanical properties of hydrogels significantly increased after incorporation of
      Q-TCNCs. Moreover, the nanocomposite hydrogels exhibited partly recoverable
      ability due to the presence of reversible electrovalent bonds in the hydrogel
      networks.

PMID- 28504130
TI  - Bifidobacterial growth stimulation by oligosaccharides generated from olive tree
      pruning biomass.
AB  - This work aims to evaluate the prebiotic potential of oligosaccharides (OS)
      obtained from autohydrolysis of olive tree pruning biomass (OTPB). Two selected
      fractions (F1 and F2) were characterized and used in in vitro fermentations by
      two Bifidobacterium spp. (B. adolescentis and B. longum) and one fecal inoculum.
      The fraction F1 presented a lower average degree of polymerization (DP) mainly
      with OS ranging from 3 to 6 DP, whereas the fraction F2 corresponded to a pool of
      unsubstituted and acetylated oligomers with DP between 4 and 19. In the
      fermentation by Bifidobacterium, F1 supported a higher biomass formation, OS
      consumption and organic acids production than F2. With the fecal inoculum, the
      accumulation of organic acids, as the sum of acetate, propionate and butyrate,
      was similar for F1 and F2 (107 and 101mM, respectively). The bifidobacteria
      counts also increased during the incubation time for both OS fractions.

PMID- 28504131
TI  - Electrospun core-shell structured nanofilm as a novel colon-specific delivery
      system for protein.
AB  - A novel core-shell structured nanofilm for the delivery of protein to the colon
      was developed by coaxial electrospinning using bovine serum albumin (BSA) as
      protein model. Firstly, the BSA-loaded chitosan nanoparticle was prepared by
      ionic gelation, and then the coaxial nanofilm was fabricated using alginate as
      shell layer and the BSA-loaded chitosan nanoparticle as core layer. Scanning
      electron microscopy analysis showed that the obtained nanofilm exhibited a smooth
      surface, and the core-shell structure was evidenced by the aid of transmission
      electron microscopy. There was little change in the secondary structure of
      encapsulated BSA and around 75% of BSA was released in the simulated colonic
      fluid. The corresponding kinetics models of BSA release in different simulated
      digestive fluids were built and the results revealed that the release of BSA in
      colon followed a complex mechanism. This study shows that electrospun nanofilm is
      a promising colon-specific delivery system for bioactive protein.

PMID- 28504132
TI  - Non-destructive and direct determination of the degree of substitution of
      carboxymethyl cellulose by HR-MAS 13C NMR spectroscopy.
AB  - We report on the direct assessment of the degree of substitution (DS) of
      carboxymethyl cellulose (CMC) by High Resolution Magic Angle Spinning (HR-MAS)
      13C NMR spectroscopy. The method is applied to industrial CMCs with low and high
      viscosity and nominal DS, purified and technical samples, and from cellulose
      linters or wood. The preparation of a set of purified CMC working standards with
      accurate DS values for the method validation is also described. The DS values
      determined via HR-MAS 13C NMR on the industrial samples are critically compared
      to the corresponding values achieved through the USP 37 <281> method (ASH method)
      and the HPLC method, and the advantages and limitations of the HR-MAS NMR method
      highlighted. Finally, the HR-MAS NMR approach allowed the accurate DS assessment
      in CMC with low DS, characterized by a non-negligible fraction of non
      functionalized cellulose. The proposed "effective DS" accounts for the DS of the
      solvent-exposed CMC.

PMID- 28504133
TI  - Nanofibrillation of deep eutectic solvent-treated paper and board cellulose
      pulps.
AB  - In this work, several cellulose board grades, including waste board, fluting, and
      waste milk container board, were pretreated with green choline chloride-urea deep
      eutectic solvent (DES) and nanofibrillated using a Masuko grinder. DES-treated
      bleached chemical birch pulp, NaOH-swollen waste board, and bleached chemical
      birch pulp were used as reference materials. The properties of the nanofibrils
      after disc grinding were compared with those obtained through microfluidization.
      Overall, the choline chloride-urea DES pretreatment significantly enhanced the
      nanofibrillation of the board pulps in both nanofibrillation methods-as compared
      with NaOH-treated pulps-and resulted in fine and long individual nanofibrils and
      some larger nanofibril bunches, as determined by field emission scanning electron
      microscopy and transmission electron microscopy. The nanofibril suspensions
      obtained from the DES pretreatment had a viscous, gel-like appearance with shear
      thinning behavior. The nanofibrils maintained their initial crystalline structure
      with a crystallinity index of 61%-47%. Improved board handsheet properties also
      showed that DES-treated and Masuko-ground waste board and paper nanocellulose can
      potentially enhance the strength of the board. Consequently, the DES chemical
      pretreatment appears to be a promising route to obtain cellulose nanofibrils from
      waste board and paper.

PMID- 28504134
TI  - Morphology, transport characteristics and viscoelastic polymer chain confinement
      in nanocomposites based on thermoplastic potato starch and cellulose nanofibers
      from pineapple leaf.
AB  - Eco-friendly "green" nano composites were fabricated from potato starch and
      cellulose nanofibers from pineapple leaf. Nanocomposites of starch/cellulose
      nanofibers were prepared by solution mixing followed by casting. The
      investigation of the viscoelastic properties confirms starch macromolecular chain
      confinement around the nano scale cellulose surface, superior dispersion and very
      good interaction between thermoplastic starch and cellulose nanofibers. The
      degree of chain confinement was quantified. The chain confinement was associated
      with the immobilization of the starch macromolecular chains in the network formed
      by the nano-scale cellulose fibers as a result of hydrogen boding interactions.
      From the results, it was assumed that the starch glycerol system exhibits a
      heterogenous nature and cellulose nanofibers tend to move towards glycerol rich
      starch phase. Barrier properties also improved with the addition of nanofiller up
      to 3wt.% but further addition depreciated properties due to possible fiber
      agglomeration. The kinetics of diffusion was investigated and typical kinetic
      parameters were determined and found that the nanocomposites follow pseudo
      fickian behaviour. The outcome of the work confirms that the prepared
      nanocomposites films can be used as a swap for packaging applications.

PMID- 28504135
TI  - A versatile method for the surface tailoring of cellulose nanocrystal building
      blocks by acylation with functional vinyl esters.
AB  - Herein we propose a versatile method for the surface tailoring of cellulose
      nanocrystals (CNCs) based on the reactivity of vinyl ester molecules toward the
      accessible hydroxyl groups located at the surface of the nanoparticles. CNCs
      produced from wood pulp were acylated in various conditions, with potassium
      carbonate as catalyst and under microwave activation. The impact of solvent,
      temperature and reagent concentration on the reaction efficiency and kinetics was
      then investigated, using vinyl acetate as a model vinyl ester. Results indicated
      that the chemical reactivity was significantly influenced by the quality of the
      CNCs dispersion in the solvent of reaction, the ratio of reagent relative to the
      CNCs surface OH groups, the diffusion of reagent and catalyst within the CNCs
      aggregates, and the different nucleophilic strengths of the surface hydroxyl
      groups. The versatility of the method was verified by extending the reaction to a
      selection of vinyl esters bearing various functionalities.

PMID- 28504136
TI  - Fabrication of Sustained-release CA-PU Coaxial Electrospun Fiber Membranes for
      Plant Grafting Application.
AB  - Plant grafting is a well-known activity in orchards, greenhouses and vineyards
      gardens. However, low survival rate still limits the promotion of grafting and
      breeding of improved varieties. We report on polymeric fibers, obtained through
      coaxial electrospun, as carriers for the sustained release of drugs to heal
      wounds in plants. The CA-PU co-electrospun fibers show a rather uniform diameter,
      a smooth and hydrophilic surface. As long as 10days of sustained drugs release
      meets with the physiological requirement of plant grafting. The callus toxicity
      test shows that the CA-PU fibers are not toxic for plant cells. We show that
      loading the core of CA-PU fibers with 6-Benzylaminopurine (6-BA), a first
      generation synthetic cytokinin that elicits plant growth and development, results
      in fibers that can efficiently promote the healing of plant wounds, thereby
      significantly improving the grafting survival rate.

PMID- 28504137
TI  - Gelation of Na-alginate aqueous solution: A study of sodium ion dynamics via NMR
      relaxometry.
AB  - Sodium alginate (SA) hydrogels have a wide range of applications including tissue
      engineering, drug delivery and formulations for preventing gastric reflux. The
      dynamics of sodium ions during the gelation process of SA solution is critical
      for clarification of the gelation procedure. In this work, nuclear magnetic
      resonance (NMR) relaxometry and pulsed-field-gradient (PFG) NMR diffusometry were
      used to investigate the dynamics of the sodium ions during the gelation of SA
      alginate. We find that sodium ions are in two different states with the addition
      of divalent calcium ions, corresponding to Ca2+ crosslinked and un-crosslinked
      regions in the hydrogels. The sodium ions within the un-crosslinked regions are
      those released from the alginate chains without Ca2+ crosslinking. The relative
      content of sodium ions within the Ca2+ crosslinked regions decreased with the
      increase in the content of calcium ions in the system. The relaxation time T2 of
      sodium ions within the Ca2+ crosslinked and un-crosslinked regions shift to
      shorter and longer relaxation time with the increase in concentration of calcium
      ion, which indicates the closer package of SA chains and the larger space for the
      diffusion of free sodium ions. This work clarifies the dynamics of 23Na+ in a
      calcium alginate gel at the equilibrium state.

PMID- 28504138
TI  - Hybrid pectin-based biosorbents for zinc ions removal.
AB  - In this paper, a set of the hybrid biosorbents, made of pectin and polysaccharide
      additives (arabic, tragacanth, guar, karaya, xanthan, gellan, carob gums, agar
      agar) or lecithin (phospholipid), was investigated and tested for zinc ions
      removal. The immobilization of the polysaccharides into the pectin matrix was
      proved by the IR spectroscopy. The structure of the working biosorbents was
      observed in SEM micrographs. The influence of the additive type and pH on the
      sorption properties and swelling index was investigated. The maximum sorption
      capacities were achieved in pH above 4 and ranged from 17.7 to 25.4mg/g for
      lecithin and xanthan gum as additives, respectively. The results show that the
      hybrid pectin-based beads are promising biosorbents for zinc removal from aqueous
      solutions.

PMID- 28504139
TI  - The protective role of phytate in the oxidative degradation of cereal beta
      glucans.
AB  - This study investigated the role of phytate in the Fenton reaction induced
      oxidative degradation of cereal beta-glucan. Viscosity analysis showed that the
      degradation rate was high in the beginning of oxidation, which fitted to the
      second order kinetic model. Oat beta-glucan contained significant amount of
      residual phytate and after the residual phytate was removed, faster degradation
      was shown compared to the original oat beta-glucan. Adding the same amount of
      phytic acid (PA) to the phytate removed beta-glucan sample also retarded the
      degradation but not as efficiently as the residual phytate. Considerable
      retardation of viscosity loss was shown when the PA to iron ratio was high. The
      presence of ascorbic acid weakened the retardation effect of phytic acid. Thus,
      phytate can significantly improve the oxidative stability of beta-glucan when the
      ratio of phytic acid to transition metals and the presence of ascorbic acid are
      taken into consideration.

PMID- 28504140
TI  - DFT study on the dissolution mechanisms of alpha-cyclodextrin and chitobiose in
      ionic liquid.
AB  - Density functional theory (DFT) was employed to study the dissolution mechanisms
      of alpha-cyclodextrin and chitobiose in 1-ethyl-3-methyl-imidazolium acetate
      ([Emim][OAc]). Geometrical analysis of the studied complexes indicated that both
      anion and cation in ionic liquid interacting withalpha-cyclodextrin and
      chitobiose contributed to the dissolution reaction. Intermolecular interactions
      in the complexes were identified as non-covalent interactions, such as hydrogen
      bonds, van der Waals interactions and repulsions, which were considered as the
      driving force of dissolution. Among them, hydrogen bonding interactions played a
      dominant role, which was further visualized in the real space by combination of
      atoms in molecules (AIM) and reduced density gradient (RDG) techniques. The
      nature of intermolecular orbital interactions was characterized using natural
      bond orbital (NBO) theory.

PMID- 28504141
TI  - Starch/MWCNT-vitamin C nanocomposites: Electrical, thermal properties and their
      utilization for removal of methyl orange.
AB  - In the present study, the surface of multiwalled carbon nanotubes (MWCNT)s is
      modified by ascorbic acid (AA) (vitaminC) for their dispersion improvement in the
      starch matrix. Then, the starch-based nanocomposites (NCs) containing 3, 6 and
      9wt% of AS modified MWCNTs (AA-MWCNT)s were fabricated via ultrasonication
      method. Characterization of the prepared NCs was accomplished by different
      techniques. The optimum MWCNT content for the generation of fine electrical
      conductivity was found to be about 3wt%, indicating better dispersion of AA-MWCNT
      with low amount of AA-MWCNT. The adsorption efficiency of starch/AA-MWCNTs NCs is
      examined using methyl orange (MO) as adsorbate. Finally, it is concluded that
      starch/AA-MWCNTs NC is an effective adsorbent for the uptake of MO dye from
      aqueous solution.

PMID- 28504142
TI  - Prebiotic efficacy and mechanism of inulin combined with inulin-degrading
      Lactobacillus paracasei I321 in competition with Salmonella.
AB  - Inulin efficacy was proven for raising anti-Salmonella activity of the inulin
      degrading Lactobacillus paracasei I321 (infant isolate) through the mechanisms of
      antibacterial secretion and competitive adhesion. Inulin significantly promoted
      competitive adhesion of L. paracasei I321 against many Gram-negative foodborne
      pathogenic bacteria. Salmonella Typhimurium SA2093 was completely suppressed
      under highly competitive niche of fecal microflora when inulin, L. paracasei
      I321, and their synbiotic combination were applied. Inulin supplementation
      obviously alleviated nutrient limitation in the mimicked proximal colon leading
      to complete destruction of Salmonella. This was achieved through the manipulation
      of fecal bifidobacteria which subsequently altered antibacterial metabolites.
      Acetate was the major metabolite correlating to high number of fecal
      bifidobacteria in the presence of inulin, whereas lactate became dominant when L.
      paracasei I321 was coupled. This inulin-degrading strain was able to persist and
      dominate in the competitive environment of fecal microflora and functioned
      synergistically with inulin to completely destroy Salmonella.

PMID- 28504143
TI  - Thermal and mechanical properties of tailor-made unbranched alpha-1,3-glucan
      esters with various carboxylic acid chain length.
AB  - The convenient and environmentally friendly method for in vitro polymerization
      catalyzed by glucosyltransferase, designated as GtfJ, extracted from recombinant
      E. Coli was used to synthesize tailor-made alpha-1,3-glucan (alpha-1,3-d-glucan)
      having moderate molecular weight (Mw=2.0*105) and no branches. With the aim to
      improve thermoplasticity of this polysaccharide, after in vitro synthesis,
      chemical modification by acylation was selected and then fully substituted alpha
      1,3-glucan esters were successfully obtained via both homogeneous and
      heterogeneous methods. Thermal degradation temperature of alpha-1,3-glucan esters
      was improved after esterification and dependent on neither side chain length nor
      synthesis methods. DSC curves suggested a presence of crystal structure in alpha
      1,3-glucan acetate, propionate, butyrate, valerate and hexanoate due to
      detectable melting endotherm, whereas octanoate exhibited amorphous behavior.
      Tm's of alpha-1,3-glucan esters were relatively high, more than 200 degrees C, in
      comparison with commercial plastics. The shorter chain length of acid component,
      the higher Tm and Tg ester products exhibited. In addition, tensile strength of
      alpha-1,3-glucan esters decreased in contrast with elongation at break with an
      increase in alkyl chain length of an acid component. Thus, crystalline and
      amorphous alpha-1,3-glucan esters with adjustable thermal and mechanical
      properties obtained from this research are promising materials for continuing
      applied researches and contemplating the future application in bio-based
      thermoplastic materials.

PMID- 28504144
TI  - Low molecular weight xanthan gum suppresses oxidative stress-induced apoptosis in
      rabbit chondrocytes.
AB  - We have previously reported the application of low molecular weight XG(LM-XG),
      with molecular weights ranging from 1*106Da to 1.5*106Da for treating
      osteoarthritis. In this study, we investigated the anti-apoptotic activity of LM
      XG under oxidative stress conditions, activated by hydrogen peroxide (H2O2)
      treated chondrocytes in vitro. Chondrocytes were pretreated with various doses of
      LM-XG (0, 10, 100, 500, or 1000MUg/mL) or 1000MUg/mL sodium hyaluronate for 12h,
      and then exposed to 0.5mmol/L H2O2 for another 12h. After treatment, chondrocyte
      viability was evaluated using a cell counting kit-8; DNA fragmentation was
      detected using Hoechst33258 staining; the percentage of DNA fragmentation was
      evaluated using the diphenylamine DNA assay kit; the apoptosis rate was evaluated
      using flow cytometry; chondrocyte ultra-microscopic morphology was observed using
      transmission electron microscopy; intracellular reactive oxygen species levels
      were observed and quantified using 2,7-dichlorofuorescin diacetate, mitochondrial
      permeability transition analysis was performed using MitoTracker Red CMXRos and
      4',6-diamidino-2-phenylindole staining; and finally, caspase-3 activity was
      detected by western blot. The results showed that, compared with H2O2-treated
      chondrocytes, LM-XG improved cell viability, decreased the percentage of DNA
      fragmentation, reduced the apoptosis rate, decreased the levels of intracellular
      reactive oxygen species and mitochondrial permeability transition, reverted the
      morphological damage, and downregulated cleaved caspase-3 levels. These results
      demonstrate that LM-XG has anti-apoptotic activity in H2O2-treated chondrocytes.

PMID- 28504145
TI  - Preparation and properties of carbohydrate-based composite films incorporated
      with CuO nanoparticles.
AB  - The present study aimed to develop the carbohydrate biopolymer based
      antimicrobial films for food packaging application. The nanocomposite films of
      various biopolymers and copper oxide nanoparticles (CuONPs) were prepared by
      solvent casting method. The nanocomposite films were characterized using SEM,
      FTIR, XRD, and UV-vis spectroscopy. The thermal stability, UV barrier, water
      vapor permeability, and antibacterial activity of the composite films were also
      evaluated. The surface morphology of the films was dependent on the types of
      polymers used. The XRD revealed the crystallinity of CuONPs in the composite
      films. The addition of CuONPs increased the thickness, tensile strength, UV
      barrier property, relative humidity, and water vapor barrier property. The CuONPs
      incorporated composite films exhibited strong antibacterial activity against
      Escherichia coli and Listeria monocytogenes. The developed composite films could
      be used as a UV-light barrier antibacterial films for active food packaging.

PMID- 28504146
TI  - Lignin-coated cellulose nanocrystal filled methacrylate composites prepared via
      3D stereolithography printing: Mechanical reinforcement and thermal
      stabilization.
AB  - Various contents of lignin-coated cellulose nanocrystals (L-CNC) were
      incorporated into methacrylate (MA) resin and their mixture was used to prepare
      nanocomposites via 3D stereolithography (3D-SL) printing. Gaps were found between
      the L-CNC and MA matrix in 3D-SL printed nanocomposites before postcure. However,
      gaps decreased after postcure due to interactions between the L-CNC and MA
      molecules. Mechanical properties increased with the addition of 0.1% and 0.5% L
      CNC after postcure, and the thermal stability was improved at 0.5% L-CNC. Dynamic
      mechanical analysis demonstrated that incorporation of L-CNC increased the
      storage modulus in the rubbery plateau. The loss factor had two transition
      regions, which gradually changed by merging together with increasing L-CNC
      content, and a broadening of the transition region was observed after postcure.
      In particular, the mechanical and thermal properties of 3D-SL printed
      nanocomposites, after postcure, exhibited higher improvement than those before
      postcure.

PMID- 28504147
TI  - Synthesis and characterization of cellulose-goethite composites and their
      adsorption properties with roxarsone.
AB  - This study reports on the preparation of goethite and its supported forms onto
      cellulose as adsorbents for the adsorption of 4-hydroxy-3-nitrobenzene arsenic
      acid (roxarsone) from aqueous solution. Goethite nanoparticles (NPs) and their
      cellulose composites were prepared with good yield ~97%, and characterized by
      thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR)
      spectroscopy, Raman spectroscopy, nitrogen gas adsorption/desorption (BET),
      powder X-ray diffraction (pXRD) and transmission electron microscopy (TEM). The
      monolayer uptake (Qm) capacity of goethite was 19.2mg/g while the Qm value for
      30% Fe coated goethite-cellulose (GC) was 17.4mg/g. The greater content and
      dispersion of goethite NPs contribute active sites on the cellulose surface to
      yield greater uptake of roxarsone for the Fe loaded GC composites. GC composites
      are a cost effective and efficient way to disperse goethite NPs onto cellulose
      surface for the enhanced adsorption of roxarsone. The GC composites reduce NP
      leaching whilst maintaining comparable uptake of arsenic species at 30% iron
      oxide doping that rival the adsorption properties of the pure mineral phase of
      goethite.

PMID- 28504148
TI  - Enhanced emulsifying properties of wood-based cellulose nanocrystals as Pickering
      emulsion stabilizer.
AB  - Cellulose nanocrystals are hydrophilic nanomaterials, which limits their
      applications as interfacial compounds. Herein, we propose using modified wood
      based cellulose nanocrystals as Pickering emulsion stabilizer. Wood cellulose was
      consecutively oxidized and modified with phenyltrimethylammonium chloride to
      create hydrophobic domains comprised of phenyl groups. These modified oxidized
      cellulose nanocrystals (m-O-CNCs) were homogeneous/electrostatically stable in
      water and they can stabilize O/W Pickering emulsions. The dispersed phase volume
      fraction (DPVF) of the Pickering emulsion was 0.7 at around 1.5g/L, whereas the
      tween-20 control needed a 13-fold greater concentration to have a similar DPVR.
      In addition, these m-O-CNC stabilized Pickering emulsions also showed good
      mechanical and thermal stability against centrifugation and heat, as well as size
      controllability. In terms of stability, size controllability, surfactant-free
      status, these m-O-CNCs possess superior and enhanced emulsifying properties.
      Future research for these new interfacial materials have potential in
      applications, for personal care, cosmetic and pharmaceutic industries.

PMID- 28504149
TI  - Post-screening characterisation and in vivo evaluation of an anti-inflammatory
      polysaccharide fraction from Eucommia ulmoides.
AB  - We report here the discovery of a polysaccharide, namely EUP1, with anti
      inflammatory activity from the herb of Eucommia ulmoides Oliv. We separated three
      polysaccharide fractions from this herb based on acidity and screened them for
      their activity in modulating the phenotype of murine macrophages. Among them,
      EUP1 was the only fraction to exert such a function - it stimulated Raw 264.7
      cells to express CD206 and a key anti-inflammatory cytokine interleukin-10.
      Having fully characterised EUP1 with a series of chromatographic and
      spectroscopic analyses, we evaluated its anti-inflammatory effects in both in
      vitro and in vivo inflammatory models. In the murine model of sepsis induced by
      lipopolysaccharide, administration of EUP1 effectively suppressed the expression
      of major inflammatory cytokines, alleviated lung injury and increased animal
      survival rate. In summary, EUP1, with a clearly elucidated chemical structure and
      solid anti-inflammatory activity, may become a valuable candidate for further
      development into an anti-septic therapeutic agent.

PMID- 28504150
TI  - Characteristics of unique HBr-hydrolyzed cellulose nanocrystals from freshwater
      green algae (Cladophora rupestris) and its reinforcement in starch-based film.
AB  - Cellulose nanocrystals (CNCs) are promising materials that are readily extracted
      from plants and other cellulose-containing organisms. In this study, CNCs were
      isolated from freshwater green algae (Cladophora rupestris) thriving in a
      volcanic lake, using hydrobromic acid (HBr) hydrolysis. Morphological and
      structural studies revealed highly crystalline CNCs (94.0% crystallinity index)
      with preferred orientation to [100] lattice plane as shown by XRD measurements
      and have an average diameter of 20.0 (+/-4.4)nm as shown by TEM. Thermal studies
      showed increased temperature for thermal decomposition of CNCs (381.6 degrees C),
      which is a result of HBr hydrolysis for CNCs isolation. The isolated CNCs were
      reinforced into starch based biocomposites via solution casting and evaporation
      method. Mechanical strength was improved as high as 78% upon addition of 1%
      cellulose nanocrystals in the films. The produced films are promising materials
      for their high mechanical strength, biodegradability and availability of raw
      materials.

PMID- 28504151
TI  - The fabrication of microcrystalline cellulose-nanoZnO hybrid composites and their
      application in rubber compounds.
AB  - Microcrystalline cellulose (MCC) was first swollen and then hybridized with nano
      ZnO to prepare MCC-ZnO hybrid composites using a microreactor technique. The
      microstructure of the ZnO particles was controlled and characterized. The results
      showed that the nano-ZnO particles had a Wurtzite structure and were successfully
      loaded on the surface of the MCC, and the ZnO morphologies could be shaped as
      spheres, rods or tubes by controlling the size of microreactor. The hybrid ratio
      of ZnO was approximately 20%. The MCC-ZnO hybrids were used in SSBR2557A/SiO2
      compounds to replace portions of the silica. The results showed that MCC-ZnO
      compounds had improved processing and mechanical properties compared to the pure
      MCC sample. The dynamic mechanical analysis (DMA) indicated that MCC-ZnO
      compounds had higher wet-skid resistance and lower rolling resistance than the
      control samples. The interfacial bonding between the hybrids and rubber was also
      improved; the sizes of the hybrid composites decreased in situ during the rubber
      processing.

PMID- 28504152
TI  - Impact of diverse cultivars on molecular and crystalline structures of rice
      starch for food processing.
AB  - The objective of this study was to determine the molecular and crystalline
      structures of starches from diverse rice cultivars for three major food
      processing in Korea (cooked rice, brewing and rice cake). Rice starches were
      isolated from 10 different rice varieties grown in Korea. Apparent amylose
      contents of rice starches from cooked rice, brewing and rice cake varieties were
      21.1-22.4%, 22.9-24.6%, and 20.1-22.0%, respectively. Rice starches from rice
      cake varieties showed higher peak viscosity but lower pasting temperature than
      those from cooked rice and brewing varieties. Swelling factor at 80 degrees C of
      rice starches from cooked rice, brewing and rice cake varieties was 16.6-19.0,
      17.8-19.3, and 17.8-19.2, respectively. Based on structure and physicochemical
      properties of rice starches extracted from different rice varieties, principal
      component analysis (PCA) results showed that these rice varieties could be
      clearly classified according to processing adaptability for cooked rice and rice
      cake.

PMID- 28504154
TI  - Simply constructed chitosan nanocarriers with precise spatiotemporal control for
      efficient intracellular drug delivery.
AB  - A novel intelligent nanocarrier with pH and redox sensitivities was developed
      based on Carboxymethyl-chitosan (CMCS) and thioglycolic acid conjugated chitosan
      (TCS) to provide precise spatiotemporal control for efficient intracellular
      delivery. Doxorubicin (DOX) loaded nanocarriers (DOX/CMCS-TCS NPs) were simply
      prepared by ionic gelation and then oxidation crosslink. The nanocarriers
      exhibited decent stability at pH 7.4 for up to 3days and underwent aggregation
      under acidic pH (5.5) due to protonation of the carboxyl groups on CMCS. The TCS
      skeleton was stable at pH 5.5 (mimic endo/lysosomes) but disintegrated in the
      presence of 10mM glutathione (GSH) at pH 7.4 (mimic cytosol). In vitro DOX
      release from DOX/CMCS-TCS NPs was enhanced at pH 5.5 compared with physiological
      condition, with 64.2% and 31.6% DOX released in 2h, respectively. While 85.2% of
      DOX was released within 2h as treated with 10mM GSH, suggesting the release was
      closely associated with structural disintegration of nanocarriers. The maximum
      release of DOX was obtained at 10mM GSH and pH 5.5 with 92.3% of DOX released in
      5h. Confocal laser scanning microscopy observation indicated that DOX/CMCS-TCS
      NPs efficiently escaped from endo/lysosomes within 1h incubation with MCF-7 cells
      and gave the best performance in delivering DOX into nucleus in 2h. Anticancer
      activity assay revealed that DOX/CMCS-TCS NPs had comparable or even better
      inhibition of cell viability at high drug concentrations than free DOX, with the
      IC50 of 0.6MUg/mL following 48h incubation. In summary, the simply constructed
      DOX/CMCS-TCS NPs could not only respond to intracellular delivery temporally,
      they also achieve rapid release spatially in nucleus, which provide a precise
      spatiotemporal control of drug delivery for cancer therapy.

PMID- 28504153
TI  - Injectable hyaluronic acid/poly(ethylene glycol) hydrogels crosslinked via strain
      promoted azide-alkyne cycloaddition click reaction.
AB  - This paper reports injectable hyaluronic acid (HA)-based hydrogels crosslinked
      with azide-modified poly(ethylene glycol) (PEG) via the strain-promoted azide
      alkyne cycloaddition (SPAAC) between cyclooctyne and azide groups. Cyclooctyne
      modified HA (Cyclooctyne-HA) is prepared by the reaction of HA with 2
      (aminoethoxy)cyclooctyne. To crosslink the modified HA, quadruply azide
      terminated poly(ethylene glycol) (Azide-PEG) is designed and prepared. The
      mixture of Cyclooctyne-HA and Azide-PEG gelates in a few minutes to form a strong
      HA-PEG hydrogel. The hydrogel has fast gelation time, good strength, and slow
      degradation rate, because of the high reactivity of SPAAC, high crosslinking
      density originated from the quadruply-substituted Azide-PEG, and the good
      stability of the crosslinking amide bonds. In vitro cell culturing within the
      hydrogel demonstrated an excellent cell-compatibility. The bioorthogonality of
      SPAAC makes the hydrogel injectable. With good mechanical properties and
      biocompatibility, the hydrogel would be useful in a wide range of applications
      such as injection filling materials for plastic surgery.

PMID- 28504155
TI  - Structural and physicochemical properties of granular starches after treatment
      with debranching enzyme.
AB  - The present study modified maize and potato granular starches by partial
      debranching treatment below the gelatinization temperature, and investigated
      their structural and physicochemical properties. Pullulanase was much effective
      (more than three times) on hydrolyzing potato starch compared to maize starch as
      measured from total carbohydrate values in the supernatant. The pullulanase
      hydrolysis decreased the amount of double helices as observed from DSC
      measurement. These effects were dependent upon the time of enzyme hydrolysis
      (24h>8h>1h) as well as type of starch (potato>maize). The pullulanase hydrolysis
      decreased the peak viscosity of the potato starch paste, whereas the effect was
      very less pronounced for maize starch. The current results showed that it is
      possible to achieve the starches with desired physicochemical properties by
      varying the starch type as well as modification process.

PMID- 28504156
TI  - Poly(N-methacryloyl glycine)/nanocellulose composites as pH-sensitive systems for
      controlled release of diclofenac.
AB  - The present study reports the development of non-cytotoxic and pH-sensitive
      nanostructured membranes consisting of a polymer with amino acid pending moieties
      and bacterial nanocellulose (BC). The nanocomposites were prepared through a
      simple methodology under green reaction conditions. The obtained materials
      display good thermal stability (up to 200 degrees C), viscoelastic (storage
      modulus>700MPa) and mechanical (Young's modulus=3.5-4.9GPa) properties, together
      with high water uptake capacity. The results of the in vitro MTT assay showed
      that the nanocomposites are non-cytotoxic to HaCaT cells for 72h. The in vitro
      release profile of diclofenac sodium salt (DCF) from the nanocomposites into
      simulated body fluids at different pH values demonstrates the pH-responsive
      behaviour of these materials. Besides, DCF is mainly retained in the
      nanocomposites at pH 2.1 and released at pH 7.4, revealing their potential for
      the controlled release of DCF in dermal as well as in oral drug delivery
      applications.

PMID- 28504157
TI  - Biomacromolecular-based ionic-covalent hydrogels for cell encapsulation: The
      atelocollagen - Oxidized polysaccharides couples.
AB  - Mixed crosslinked networks of ionic-covalent entanglement type were prepared
      starting from ternary mixtures of atelocollagen (aK; as fibrillary matrix
      generator), sodium hyaluronate (NaHyal; a microfibrillation assistant), and
      oxidized polysaccharides (OxPolys; as both cross-linkers and matrix fillers), and
      were tested as hydrogels for eukaryotic cell encapsulation. Either oxidized
      gellan (GellOx) or pullulan (PullOx) were used. An original procedure and optimal
      hydrogel recipes were developed to encapsulate fibroblasts and adipose-derived
      stem cells, while preserving their viability and proliferative ability during ex
      vivo temporarily storage. Physical-chemical, rheological, and biocompatibility
      properties of the prepared hydrogels were compared against the classic alginate
      hydrogel used for cell encapsulation. A larger range of material characteristics
      (from lax to stiff) and better laboratory maneuverability were demonstrated,
      which permit to design appropriate compositions for particular cell types. All
      hydrogels undergo fast liquefaction at temperatures between 42 and 50 degrees C,
      permitting the cell release after a short innocuous thermal shock.

PMID- 28504158
TI  - Influence of osmotic and weight pressure on water release from polysaccharide
      ionic gels.
AB  - Kappa-carrageenan (kC) is a polyelectrolyte biopolymer that forms gels if the kC
      concentration, the salt and the temperature are adequately chosen. Actually,
      under certain conditions, kC gels release water in a process called syneresis. In
      this contribution, the syneresis of gels containing 2g/L of kC has been studied
      as a function of potassium chloride concentration [KCl]. The syneresis decreases
      if the [KCl] is increased in the biopolymer solution (sol) before the gelation
      but increases if the [KCl] is increased after gelation by immersing the gels in
      KCl solution. The surrounding phase induces an osmotic pressure (Pi), which
      increases if the [KCl] difference between the inside and outside of the gel
      increases. Swelling has been observed for negative Pi. A method that enables the
      exudate to be removed continuously demonstrated the effect of the strain caused
      by the gel's own weight on syneresis. Increasing the KCl concentration in the sol
      promotes syneresis due to strain. The analysis of the syneresis kinetics of
      different systems has enabled the creation of a pressure-induced syneresis
      diagram. This diagram will contribute to controlling the mouthfeel of chewing
      products.

PMID- 28504159
TI  - Preparation and properties of zein-rutin composite nanoparticle/corn starch
      films.
AB  - Edible active films were prepared based on zein-rutin composite nanoparticles
      (RNs) and corn starch (CS). RNs (0, 0.5, 1, 2, 4, and 10%, w/w) were incorporated
      into CS films, to act as a natural antioxidant. Scanning electron microscopy and
      Fourier-transform infrared spectroscopy were used to examine the morphology and
      functional group interactions. The tensile strength and elongation at break
      increased from 1.19 to 2.42MPa, and from 42.10 to 78.84%, respectively, with
      increasing RN loading. The incorporation of RNs led to the formation of a net
      like structure, which decreased the water vapor permeability and water solubility
      of the RN-CS film. The cumulative amount of rutin detected in vitro after 12h was
      27.1-36.9% of the total amount of rutin. The RNs dispersed in the CS film
      provided controlled release of rutin. The antioxidant capacities of the films
      were greater than that of the pure CS film.

PMID- 28504160
TI  - Effect of molecular weight on the ability of guar gum to enhance "weak gel"
      rheology of microdispersed oxidised cellulose (MDOC).
AB  - MDOC comprises small, essentially insoluble, particles which associate to form
      "weak gel" networks at concentrations above ~4wt%. Association is promoted by
      guar gum, causing an increase in G' at low levels of addition and a decrease at
      higher concentrations, due to excessive aggregation of the MDOC particles. For
      guar gum samples with molecular weights ranging from ~60 to ~1800kDa, we found
      that the concentration required to give maximum G' for 5wt% dispersions of MDOC
      increased systematically from ~0.005wt% for the lowest molecular weight to
      ~0.3wt% for the highest. We propose that guar gum drives self-association of MDOC
      to reduce enthalpically-unfavourable (segregative) interactions between the two
      materials, and that large coils are less effective than smaller ones because a
      higher proportion of chain sequences are buried in the interior of the coil,
      where they cannot make segmental contacts with the MDOC particles.

PMID- 28504161
TI  - Rapid fabrication of TiO2@carboxymethyl cellulose coatings capable of shielding
      UV, antifog and delaying support aging.
AB  - Agricultural plastic films capable of shielding UV, filtering visible light and
      antifog are important to prolong their life and protect safeties of
      agriculturists and crops. In this work, high stable and small size TiO2@polymer
      nanoparticles (NPs) were prepared by an efficient one-pot microwave synthesis
      using titanic sulfate as Ti resource, carboxymethyl cellulose sodium (CMC) as
      complexing agent and stabilizer. The TiO2@CMC NPs obtained were then utilized to
      fabricate poly(ethylene imine) (PEI)/TiO2@CMC coatings on the surface of
      polypropylene films by a layer-by-layer assembly technique. The TiO2@CMC NPs show
      rapid deposition rate because small, spherical and anion-rich TiO2@CMC NPs
      possess large specific surface area and fast diffusion rate. More importantly,
      property experiments confirm that (PEI/TiO2@CMC)*15 coatings can not only
      effectively shield UV rays, filter visible light and prevent fogging but also
      delay the aging of their supports.

PMID- 28504162
TI  - Purification of glucomannan from salep: Part 2. Structural characterization.
AB  - The aim of this study was to investigate the effects of different extraction
      temperatures (25, 55 and 85 degrees C) on the structural characteristics of
      glucomannan (GM) purified from salep. All extraction conditions reduced protein
      content and molecular weight of salep. The effectiveness of removing the
      impurities and the highest purity of GM25 were observed with size exclusion
      profile. FTIR experiments demonstrated the presence of acetyl group, reduction of
      protein content and increment of polymer interaction of GM25. XRD patterns of
      GM25 with narrower and higher intensity than GM55, GM85 and native salep
      indicated strengthened interaction of GM25. Higher particle size was determined
      for GM25. The degradation peak observed with DSC increased from 293 to 314
      degrees C and GM25 had the higher thermal stability which was also supported with
      TGA results. These results could provide widening the applications in food
      industry and other fields and also progressing development of salep with a better
      structural characteristic.

PMID- 28504163
TI  - Effects of immobilization, pH and reaction time in the modulation of alpha-, beta
      or gamma-cyclodextrins production by cyclodextrin glycosyltransferase: Batch and
      continuous process.
AB  - This study reports the immobilization of a beta-CGTase on glutaraldehyde pre
      activated silica and its use to production of cyclodextrins in batch and
      continuous reactions. We were able to modulate the cyclodextrin production (alpha
      , beta- and gamma-CD) by immobilization and changing the reaction conditions. In
      batch reactions, the immobilized enzyme reached to maximum productions of 4.9mgmL
      1 of alpha-CD, 3.6mgmL-1 of beta-CD and 3.5mgmL-1 of gamma-CD at different
      conditions of temperature, pH and reaction time. In continuous reactor, varying
      the residence time and pH it was possible to produce at pH 4.0 and 141min of
      residence time preferentially gamma-CD (0.75 and 3.36mgmL-1 of alpha- and gamma
      CD, respectively), or at pH 8.0 and 4.81min alpha- and beta-CDs (3.44 and
      3.51mgmL-1).

PMID- 28504164
TI  - A novel water-based process produces eco-friendly bio-adhesive made from green
      cross-linked soybean soluble polysaccharide and soy protein.
AB  - In this study, an eco-friendly soy protein adhesive was developed that utilized
      two components from soybean meal without addition of any toxic material. A plant
      based, water-soluble and inexpensive soybean soluble polysaccharide was used as
      the novel renewable material to combine with soy protein to produce a soy protein
      adhesive. Three-plywood was fabricated with the resulting adhesive, and its wet
      shear strength was measured. The results showed the wet shear strength of plywood
      bonded by the adhesive reached 0.99MPa, meeting the water resistance requirement
      for interior use panels. This improvement was attributed to the following
      reasons: (1) Combination of cross-linked soybean soluble polysaccharide and soy
      protein formed an interpenetrating network structure, improving the thermal
      stability and water resistance of the cured adhesive. (2) Adding CL-SSPS
      decreased the adhesive viscosity to 15.14Pas, which increased the amount of the
      adhesive that penetrate the wood's surface and formed more interlocks.

PMID- 28504165
TI  - Calcium silicate nanowires - An effective alternative for improving mechanical
      properties of chitosan-hydroxyethyl methacrylate (HEMA) copolymer nanocomposites.
AB  - Nanowires of calcium silicate were successfully synthesized by ultrasonic
      irradiation process and incorporated into chitosan and hydroxyetheyl methacrylate
      (HEMA) copolymer matrix by solution blending for efficacious preparation of
      biodegradable nanocomposites. Remarkable improvement in mechanical properties of
      the nanocomposites was noticed after micro-tensile analysis. Enlarged surface
      area and higher aspect ratio of CaSiO3 nanowires were the key factors responsible
      for such improvement. This was supported by EDS and XRD analysis in terms of
      proper distribution of nanofiller through the copolymer matrix and corresponding
      rise in percentage crystallanity respectively. Contact angle and biodegradation
      studies further clarified that nano-CaSiO3 did not affect the hydrophilicity and
      general degradation route of chitosan copolymer respectively. This renders the
      nano-CaSiO3 as an ideal substitute for preparing high performance nanocomposites
      to be applicable for biomedical applications.

PMID- 28504166
TI  - Functionality of chitosan in batter formulations for coating of fish sticks:
      Effect on physicochemical quality.
AB  - Chitosan is a natural polymer having diverse applications in food industry. The
      present study was undertaken to evaluate chitosan as a hydrocolloid in batter
      composition in developing enrobed fish sticks with better functional properties
      and improved quality. Different concentrations of chitosan gel were made in
      acetic acid medium and incorporated into batter for making enrobed fish sticks.
      Coating parameters, fat uptake, oil reduction, chemical quality parameters,
      instrumental texture analysis and colour were studied. Addition of chitosan gel
      had a significant effect (P<0.05) on the coating pickup, adhesion degree and
      cooking yield of the product. Total volatile basic nitrogen, pH, lipid oxidation
      parameters like peroxide value and thiobarbituric acid reactive substances of par
      fried fish sticks also showed significant differences. The oil reduction in par
      fried samples were 36.84, 65.05, 73.83, 77.65% respectively for 0.5, 1.0, 1.5,
      2.0% chitosan added samples. Addition of chitosan significantly reduced
      crispness, gumminess, Warner-Bratzler shear force and toughness (P<0.05) of the
      product. The study clearly demonstrated that the inclusion of chitosan at 1.0% in
      batter can improve functional and other quality aspects of enrobed products.

PMID- 28504167
TI  - Antibacterial and antioxidative activity of O-amine functionalized chitosan.
AB  - Cinnamaldehyde was immobilized to O-amine functionalized chitosan via a coupling
      reaction. Fourier transform infrared spectroscopy confirmed N-cinnamyl
      substitution. Wetting analyses demonstrate more hydrophobicity in the N-cinnamyl
      substituted O-amine functionalized chitosan compared to chitosan or unsubstituted
      O-amine functionalized chitosan. Thermal gravimetric analysis and differential
      scanning calorimetry demonstrates that the prepared N-cinnamyl substituted O
      amine functionalized chitosan exhibits higher thermostability than unmodified
      chitosan at temperatures in which polysaccharides are commonly stored and
      utilised. The N-cinnamyl substituted O-amine functionalized chitosan, against
      four different bacteria strains [two gram-positive (Staphylococcus aureus and
      Bacillus cereus) and two gram-negative (Escherichia coli and Pseudomonas
      aeruginosa)], displays promotion of inhibition activity against these bacterial
      strains. Finally, the antioxidative activity of the N-cinnamyl substituted O
      amine functionalized chitosan was compared with those activities of chitosan and
      O-amine functionalized chitosan. This was evaluated by uninhibited and inhibited
      hyaluronan degradation and ABTS assay. The N-cinnamyl substituted O-amine
      functionalized chitosan shows a lower activity towards donating a hydrogen
      radical compared to chitosan or O-amine functionalized chitosan. On the other
      hand, the N-cinnamyl substituted O-amine functionalized chitosan exhibited a
      higher ability to scavenge the ABTS+ cation radical compared to chitosan and O
      amine functionalized chitosan.

PMID- 28504168
TI  - Binding efficacy and kinetics of chitosan with DNA duplex: The effects of
      deacetylation degree and nucleotide sequences.
AB  - The binding process of DNA duplex with various types of chitosan polymers were
      studied at atomic level through molecular dynamics simulations. The interaction
      kinetics and binding strength, complex morphology and DNA structure evolution
      were systematically accessed. The binding efficacy of chitosan to DNA reduces
      (both in complexation speed and binding strength) when deacetylation degree is
      decreased, because protonated amine groups on chitosan backbone are more prone to
      bind with DNA, especially the phosphate oxygen, through coulomb interaction. The
      Watson Crick hydrogen bonds of A-T base pairs are more easily to break because
      chitosan is capable to form competitive hydrogen bonds with them. It is
      surprising to find that the G-C nucleotides have highly restrained kinetic motion
      than that of A-T nucleotides, which would be important for DNA-chitosan
      complexation and condensation to happen at the microscopic level. From our
      current results, the degree of chitosan deacetylation is found to play a certain
      role in regulating the DNA-chitosan complexation process, but is not as important
      as being believed before. Other types of chemical functionalization that can tune
      the chitosan's hydrophobicity should deserve more attentions in the experiment.

PMID- 28504169
TI  - Acid mediated chemical treatment to remove sugar from waste acid stream from nano
      crystalline cellulose manufacturing process.
AB  - Nano-crystalline cellulose (NCC) is a nano-scale biomaterial derived from highly
      abundant natural polymer cellulose. It is industrially produced by concentrated
      acid hydrolysis of cellulosic materials. However, presences of as high as 5-10%
      of sugar monomers in spent sulphuric acid during the manufacturing process, makes
      it unsuitable for such recycling or reuse of sulphuric acid. Currently, the
      industry has been using membrane and ion exchange technology to remove such
      sugars, however, such technologies cannot achieve the target of 80-90% removal.
      In the current investigation, thermal treatment and acid mediated thermal
      treatment have been evaluated for sugar removal from the spent sulphuric acid.
      Almost complete removal of sugar has been achieved by this approach. Maximum
      sugar removal efficiency (99.9%) observed during this study was at 120+/-1
      degrees C for 60min using 0.8 ratio (sample: acid) or at 100+/-1 degrees C for
      40min using 1.5 ratio.

PMID- 28504170
TI  - Preparation of multifunctional chitin nanowhiskers/ZnO-Ag NPs and their effect on
      the properties of carboxymethyl cellulose-based nanocomposite film.
AB  - Chitin nanowhiskers (ChNW) were isolated and used for the synthesis of hybrid
      ChNW/ZnO-Ag NPs. The hybrid nanoparticles were used for the preparation of
      multifunctional carboxymethyl cellulose (CMC) films. A ChNW was needle shape with
      the width of 8-40nm, the length of 150-260nm, and crystallinity index of 93.6%.
      The ZnO-Ag NPs were spherical with the diameter of 10.5-16.2nm. STEM, EDX, XRD,
      and UV-vis analyses confirmed the formation of ZnO-Ag NPs on the surface of ChNW.
      The thermal stability of ChNW was increased by incorporation of ZnO-Ag NPs. A CMC
      based nanocomposite film incorporated with 5wt% of ChNW/ZnO-Ag NPs was
      homogeneous and showed the high UV-barrier property. The tensile strength (TS)
      and elastic modulus (E) of the composite film increased by 18-32% and 55-100%,
      respectively, while the elongation at break (EB) decreased by 23-33%. CMC
      composite films showed strong antibacterial activity against E. coli and L.
      monocytogenes.

PMID- 28504171
TI  - Tuneable catechin functionalisation of carbohydrate polymers.
AB  - In this contribution, we present a strategy to functionalise three natural
      carbohydrate polymers (dextran - a neutral polymer, sodium alginate - an anionic
      polymer and chitosan - a cationic polymer) with catechin with excellent degrees
      of functionality. In a first step, the carbohydrate polymers were oxidised by
      sodium periodate to yield aldehyde functionalised carbohydrate polymers. The
      presence of aldehyde groups was exploited to attach catechin by an acid catalysed
      nucleophilic reaction. The degree of catechin functionalisation could be easily
      tuned by varying the acid concentration in the reaction mixture, achieving
      catechin functionalisation levels of up to 48% for dextran aldehyde catechin, 35%
      for chitosan-aldehyde-catechin and 22% for sodium alginate aldehyde catechin. 1H,
      1H-13C HSQC and DOSY NMR were performed to elucidate the structural differences
      between the three aldehyde functionalised polysaccharides and how this affects
      their reactivity and conjugation behaviour. All three carbohydrate polymer
      catechin conjugates showed superior free-radical scavenging activity compared
      with the non-functionalised polymers.

PMID- 28504173
TI  - An all-solid-state yarn supercapacitor using cotton yarn electrodes coated with
      polypyrrole nanotubes.
AB  - A novel all-solid-state yarn supercapacitor (YSC) has been fabricated by using
      the cotton yarns coated with polypyrrole (PPy) nanotubes. The interconnected
      network structure of PPy can increase the surface area as well as the
      electrode/electrolyte interface area, thus resulting in improved electrochemical
      performance. For the proposed YSC, a high areal-specific capacitance of 74.0mFcm
      2 and a desirable energy density of 7.5MUWhcm-2 are achieved. The flexibility of
      the YSC demonstrates that it is suitable for the integration as flexible power
      sources in wearable electronic textiles.

PMID- 28504172
TI  - Development of polylactic acid nanocomposite films reinforced with cellulose
      nanocrystals derived from coffee silverskin.
AB  - Bio-nanocomposite films based on polylactic acid (PLA) matrix reinforced with
      cellulose nanocrystals (CNCs) were developed using a twin-screw extruder. The
      CNCs were extracted from coffee silverskin (CS), which is a by-product of the
      coffee roasting process. They were extracted by alkali treatment followed by
      sulfuric acid hydrolysis. They were used as reinforcing agents to obtain PLA/CNC
      nanocomposites by addition at different concentrations (1%, 3%, and 5% CNCs).
      Morphological, tensile, and barrier properties of the bio-nanocomposites were
      analyzed. The tensile strength and Young's modulus increased with both 1% and 3%
      CNCs. The water vapor permeability decreased gradually with increasing addition
      of CNCs up to 3% and good oxygen barrier properties were found for all
      nanocomposites. These results suggest that CNCs from CS can improve the physical
      properties of PLA-based biopolymer film. The developed PLA/CNC bio-nanocomposite
      films can potentially be used for biopolymer materials with enhanced barrier and
      mechanical properties.

PMID- 28504174
TI  - Pineapple peel carboxymethyl cellulose/polyvinyl alcohol/mesoporous silica SBA-15
      hydrogel composites for papain immobilization.
AB  - Hydrogel composites based on pineapple peel carboxymethyl cellulose, polyvinyl
      alcohol and mesoporous silica SBA-15 were synthesized by an eco-friendly method
      of repeated freeze-thaw cycles for the application of papain immobilization. The
      experiment was optimized to obtain an efficient papain immobilization carrier.
      Simultaneously the immobilization conditions, including enzyme concentration, pH,
      crosslinker concentration and cross-linking time were optimized. The immobilized
      papain had maximum activity at low reaction temperature of 40 degrees C and
      showed pH-sensitivity by exhibiting a rapid decrease of activity within a narrow
      range from pH 7.0 to pH 7.5. Compared with the free papain, the immobilized
      papain revealed enhanced pH, thermal and storage stability. After 2h incubation
      at 80 degrees C, the immobilized papain retained 56% of its initial activity
      while the free papain only retained 16%. After 10days of storage, 79% of the
      initial activity was retained for the immobilized papain while only 27% for the
      free papain.

PMID- 28504175
TI  - Sulfoethylated nanofibrillated cellulose: Production and properties.
AB  - Sulfoethylated nanofibrillated cellulose (NFCSulf) was produced by an
      industrially relevant process. The properties of the NFCSulf were compared with
      those of carboxymethylated nanofibrillated cellulose (NFCCarb), which has been
      identified as an attractive NFC for several industrial applications. The
      investigations revealed that NFCSulf is characterized by a higher degree of
      fibrillation and has superior redispersion properties. Furthermore, NFCSulf
      displays higher stability in varying pH values as compared to NFCCarb. Hence,
      NFCSulf may be a more attractive alternative than NFCCarb in applications such as
      rheological modifiers or adsorbing components in personal care products, in which
      the performance of NFC must remain unaffected in varying ambient conditions. The
      superior properties of NFCSulf compared to NFCCarb were proposed to be due to the
      combination of the unique chemical characteristics of the sulfoethylated reagent,
      and the larger size of the sulfonate group compared to the carboxymethyl group.

PMID- 28504176
TI  - Eco-friendly soluble soybean polysaccharide/nanoclay Na+ bionanocomposite:
      Properties and characterization.
AB  - The impact of montmorillonite (MMT) as a nanofiller at different concentrations
      (5, 10, 15wt.%) on the physicochemical and functional properties of nanocomposite
      film based on soluble soybean polysaccharide (SSPS) was investigated. The results
      showed that an increase in MMT concentration was accompanied by a decrease in
      water solubility, thickness, and elongation at break. Furthermore, tensile
      strength increased when MMT concentration was increased to 10wt.%. Atomic force
      and scanning electron micrographs showed a significant agglomeration at MMT
      15wt.%. With added MMT, the level of whiteness, greenness, and yellowness of SSPS
      film increased (P<0.05). Dynamic mechanical thermal analysis indicated that the
      storage modulus of nanocomposites increased when the MMT was increased to 10wt.%.
      Furthermore, Fourier transform infrared spectrophotometry demonstrated that no
      considerable changes occurred in the functional groups of the SSPS when MMT was
      added. Antimicrobial tests revealed that antibacterial and anti-mold activities
      were unlikely from reinforced nanocomposites.

PMID- 28504177
TI  - Corrigendum to "Biosynthesis of agar in red seaweeds: A review" [Carbohydr.
      Polym. 164 (2017) 23-30].

PMID- 28504178
TI  - Tetramethylguanidine-based gels and colloids of cellulose.
AB  - Novel and stable gels of cellulose were produced. These gels are prepared at room
      temperature by combination of cellulose and tetramethylguanidine (TMG) in
      different ratios (1:1, 1:2, 1:3 in equivalents of alcohol groups of cellulose per
      number of molecules of TMG). Detailed NMR, SEM, rheological and XRD studies of
      these gels were carried out. The concentration of cellulose in the gel,
      temperature, frequency of oscillation and shear rate were used as variables in
      order to understand the fundamentals and optimize operational conditions,
      considering their possible use as matrices for CO2 capture. Cellulose recovery
      from a specific gel was performed using ethanol as precipitating agent, leading
      to a lower crystallinity, which permits to consider this polymer in further
      studies associated to physical/chemical modification of cellulose.

PMID- 28504180
TI  - The glycogen of Galdieria sulphuraria as alternative to starch for the production
      of slowly digestible and resistant glucose polymers.
AB  - Highly branched glucose polymers produced from starch are applied in various
      products, such as peritoneal dialysis solutions and sports drinks. Due to its
      insoluble, granular nature, the use of native starch as substrate requires an
      energy consuming pre-treatment to achieve solubilization at the expense of
      process costs. Glycogen, like starch, is also a natural glucose polymer that
      shows more favorable features, since it is readily soluble in cold water and more
      accessible by enzymes. The extremophilic red microalga Galdieria sulphuraria
      accumulates large amounts of a small, highly branched glycogen that could
      represent a good alternative to starch as substrate for the production of highly
      branched glucose polymers. In the present work, we analyzed the structure
      properties relationship of this glycogen in its native form and after treatment
      with amyloglucosidase and compared it to highly branched polymers produced from
      potato starch. Glycogen showed lower susceptibility to digestive enzymes and
      significantly decreased viscosity in solution compared to polymers derived from
      starch, properties conferred by its shorter side chains and higher branch
      density. The action of amyloglucosidase on native glycogen was somewhat limited
      due to the high branch density but resulted in the production of a hyperbranched
      polymer that was virtually resistant to digestive enzymes.

PMID- 28504179
TI  - Immunomodulatory effects of xanthan gum in LPS-stimulated RAW 264.7 macrophages.
AB  - In this study, we evaluated the immunomodulatory effects of xanthan gum (XG) in
      RAW264.7 macrophages and the underlying molecular mechanisms. We used scanning
      electron microscopy (SEM) to analyze the morphology of XG-treated RAW264.7 cells
      with and without lipopolysaccharide (LPS) stimulation and investigated the
      subsequent effects on nitric oxide (NO), interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), inducible nitric oxide
      synthase (iNOS), and cyclooxygenase-2 (COX-2) levels in LPS-activated mouse
      RAW264.7 macrophages. We also analyzed the binding affinity of XG to Toll-like
      receptor 4 (TLR4) with surface plasmon resonance (SPR) analysis and observed that
      XG decreased NO, IL-6 and TNF-alpha secretion into the culture medium and iNOS
      and COX-2 protein levels induced by LPS. This study reveals a two-way
      immunomodulatory effect of XG on inflammatory mediators in RAW264.7 macrophages
      that may involve the TLR4 signal pathway, providing a pharmacological basis for
      the use of XG in the control of inflammatory disorders.

PMID- 28504181
TI  - Preparation of N, N, N-trimethyl chitosan via a novel approach using dimethyl
      carbonate.
AB  - N,N,N-trimehtyl chitosan (TMC) is a water-soluble derivate of chitosan, which has
      been widely used as a biomedical material due to its excellent biocompatibility,
      biodegradability and bacterial properties. To date, TMC can only be prepared by
      the quaternization of chitosan using alkyl halide or dimethyl sulfate. However,
      alkyl halide and dimethyl sulfate are highly toxic, cancerigenic for humans, and
      harmful to the environment. This paper puts forward a novel approach to preparing
      TMC using dimethyl carbonate as a methylation reagent in an ionic liquid. The as
      synthesized O-methyl-free TMC was characterized using NMR, FTIR, XRD and TG
      analyses. The results showed that TMC with a degree of quaternization of 9.11%
      was successfully obtained and the crystallinity of chitosan decreased with the
      increasing degree of N-methylation, the thermal stability of TMC was lower than
      that of chitosan. Furthermore, the effects of the dose of ionic liquid and
      dimethyl carbonate were disscussed.

PMID- 28504183
TI  - Enzymic degradation of hydroxyethyl cellulose and analysis of the substitution
      pattern along the polysaccharide chain.
AB  - The enzymatic degradation behavior of hydroxyethyl cellulose (HEC) samples with
      different molar substitutions (MS) values was investigated. The changes in the
      molecular structure of HEC treated with enzymatic approach in comparison to the
      native HEC were studied through nuclear magnetic resonance (NMR), fourier
      transform infrared spectra (FTIR), X-ray diffraction (XRD) and scanning electron
      microscopy (SEM) techniques and kinetics of degradation was studied by
      viscometry. The cleavage of HEC chains could be observed from FTIR and kinetics
      results. Moreover, reduce in molecular weight (Mw) of polymer and liberated
      glucose concentration was investigated by gel permeation chromatography (GPC)
      analysis during enzymatic degradation. And all these results indicated that HEC
      with lower MS is more susceptible to degrade and provided a better understanding
      of the mechanism operating during enzymatic hydrolysis of HEC by cellulases.
      Furthermore, by complete degradation and quantification of liberated glucose, the
      substitution index (SI) and the distribution of substituents along the HEC chain
      were investigated. The results suggested that the HEC samples differed in
      hydroxyethyl molar substitutions (MS) and possible distribution of the
      hydroxyethyl groups. Impressively, our efforts established a facile analytical
      method for the elucidation of the distribution of substituents along the HEC
      chain.

PMID- 28504182
TI  - Oil/water interfaces of guar gum-based biopolymer hydrogels and application to
      their separation.
AB  - Oily wastewater treatment has become a significant research subject due to
      potential environmental related applications, e.g., oil spill remedy process. In
      this paper, a natural polymer based hydrogel, prepared from guar gum (GG) and
      metaborate, was coated onto a stainless steel mesh, and the as-prepared hydrogel
      coated material was applied for oil/water separation. The strong hydrophilic GG
      hydrogel imparted excellent underwater oleophobicity and ultra-low oil adhesion.
      The results proved that the as-prepared GG hydrogel-coated material possessed
      excellent self-cleaning property and high oil/water separation efficiency.

PMID- 28504185
TI  - Comments on the finding of right non recurrent laryngeal nerve during
      thyroidectomy.

PMID- 28504184
TI  - Lessons from healthcare utilization in children with obstructive sleep apnoea
      syndrome.
AB  - INTRODUCTION AND OBJECTIVES: Paediatric Obstructive Sleep Apnoea-Hypopnoea
      Syndrome (OSAS) is a multisystemic condition affecting child's health status that
      may be investigated analyzing demand for healthcare. OBJECTIVE: to quantify the
      frequency of medical consultations in children with OSAS over a 5-year period,
      compared to a healthy population. METHODS: A longitudinal, case-control,
      ambispective study was conducted at a hospital pertaining to the national public
      health system. 69 consecutive children referred for OSAS were recruited with no
      diseases other than OSAS so that healthcare demand was purely attributed to this
      condition. Matched healthy control children were selected to compare these data.
      Data regarding frequency of the medical consultations were obtained over 5 years:
      the year of the treatment ("Year0"), 1 and 2 years before ("Year -1" and "Year 
      2" respectively), and 1 and 2 years after treatment ("Year+1" and "Year+2")
      RESULTS: Frequentation Index (FI), as ratio between the use of health services by
      OSAS children and healthy controls was 1.89 during Year-2, and 2.15 during Year-1
      (P<.05). Treatment diminishes utilization, with FI of 159 during year+1 and 1.72
      during year+2 (P<.05). The main causes of attendance were otolaryngological and
      pneumological diseases, improving after treatment. CONCLUSIONS: Children
      suffering from OSAS demand more healthcare services, at least 2 years before
      treatment, implying that the disease could be present years before we manage it.
      Therapeutic actions improve healthcare services utilization, although remain
      higher than for controls, which suggests OSAS sequelae or residual disease.

PMID- 28504186
TI  - Alagille's syndrome: Hypoplasia of posterior semicircular canals.

PMID- 28504187
TI  - Transoral oropharyngeal resection classification: Proposal of the SCORL working
      group.
AB  - INTRODUCTION AND GOALS: There has been a very significant increase in the use of
      minimally invasive surgery has in the last decade. In order to provide a common
      language after transoral surgery of the oropharynx, a system for classifying
      resections has been created in this area, regardless of the instrumentation used.
      METHODS: From the Oncology Working Group of the Catalan Society of
      Otorhinolaryngology, a proposal for classification based on a topographical
      division of the different areas of the oropharynx is presented, as also based on
      the invasion of the related structures according to the anatomical routes of
      extension of these tumours. RESULTS: The classification starts using the letter D
      or I according to laterality either right (D) or left (I). The number of the
      resected area is then placed. This numbering defines the zones beginning at the
      cranial level where area I would be the soft palate, lateral area II in the
      tonsillar area, area III in the tongue base, area IV in the glossoepiglottic
      folds, epiglottis and pharyngoepiglottic folds, area V posterior oropharyngeal
      wall and VI the retromolar trigone. The suffix p is added if the resection deeply
      affects the submucosal plane of the compromised area. The different proposed
      areas would, in theory, have different functional implications. CONCLUSIONS:
      Proposal for a system of classification by area to definedifferent types of
      transoral surgery of the oropharynx, and enable as sharing of results and helps
      in teaching this type of technique.

PMID- 28504188
TI  - Discrepancy between clinical and pathological neck staging in oral cavity
      carcinomas.
AB  - INTRODUCTION: The presence of cervical lymph node metastases in patients with
      oral cavity squamous cell carcinoma reduces survival by up to 50%. OBJECTIVE: The
      aims of this study are to assess the accuracy of clinical N staging versus
      pathological N staging and its impact on survival in order to identify predictive
      factors associated with the presence of occult neck metastases. METHODS: Outcomes
      of 105 patients with oral cavity squamous cell carcinoma who underwent surgical
      treatment of the primary tumor and neck were retrospectively evaluated. RESULTS:
      For pN0 and pN+ patients 5-year overall survival was respectively 53% and 27%;
      disease specific survival was 66% for pN0 and 33% for pN+. Patients with clinical
      negative lymph nodes were pathologically upstaged in 62% of cases. Disease
      specific survival according to staging discrepancy had statistically significant
      impact on survival (p=0.009). CONCLUSION: Clinical staging usually underestimates
      the presence of nodal disease. Neck dissection should be performed in cN0 oral
      cavity squamous cell carcinoma.

PMID- 28504189
TI  - Ezrin Ser66 phosphorylation regulates invasion and metastasis of esophageal
      squamous cell carcinoma cells by mediating filopodia formation.
AB  - BACKGROUND: Ezrin, links the plasma membrane to the actin cytoskeleton, and plays
      an important role in the development and progression of human esophageal squamous
      cell carcinoma (ESCC). However, the roles of ezrin S66 phosphorylation in
      tumorigenesis of ESCC remain unclear. METHODS: Distribution of ezrin in membrane
      and cytosol fractions was examined by analysis of detergent-soluble/-insoluble
      fractions and cytosol/membrane fractionation. Both immunofluorescence and live
      imaging were used to explore the role of ezrin S66 phosphorylation in the
      behavior of ezrin and actin in cell filopodia. Cell proliferation, migration and
      invasion of ESCC cells were investigated by proliferation and migration assays,
      respectively. Tumorigenesis, local invasion and metastasis were assessed in a
      nude mouse model of regional lymph node metastasis. RESULTS: Ezrin S66
      phosphorylation enhanced the recruitment of ezrin to the membrane in ESCC cells.
      Additionally, non-phosphorylatable ezrin (S66A) significantly prevented filopodia
      formation, as well as caused a reduction in the number, length and lifetime of
      filopodia. Moreover, functional experiments revealed that expression of non
      phosphorylatable ezrin (S66A) markedly suppressed migration and invasion but not
      proliferation of ESCC cells in vitro, and attenuated local invasion and regional
      lymph node metastasis, but not primary tumor growth of ESCC cells in vivo.
      CONCLUSION: Ezrin S66 phosphorylation enhances filopodia formation, contributing
      to the regulation of invasion and metastasis of esophageal squamous cell
      carcinoma cells.

PMID- 28504190
TI  - Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3
      gene in human cancer.
AB  - The cyclin-dependent kinase inhibitor-3 (CDKN3) gene encodes a dual-specificity
      protein tyrosine phosphatase that dephosphorylates CDK1/CDK2 and other proteins.
      CDKN3 is often overexpressed in human cancer, and this overexpression correlates
      with reduced survival in several types of cancer. CDKN3 transcript variants and
      mutations have also been reported. The mechanism of CDKN3 overexpression and the
      role of CDKN3 transcript variants in human cancer are not entirely clear. Here,
      we review the literature and provide additional data to assess the correlation of
      CDKN3 expression with patient survival. Besides the full-length CDKN3 encoding
      transcript and a major transcript that skips exon 2 express in normal and cancer
      cells, minor aberrant transcript variants have been reported. Aberrant CDKN3
      transcripts were postulated to encode dominant-negative inhibitors of CDKN3 as an
      explanation for overexpression of the perceived tumor suppressor gene in human
      cancer. However, while CDKN3 is often overexpressed in human cancer, aberrant
      CDKN3 transcripts occur infrequently and at lower levels. CDKN3 mutations and
      copy number alternation are rare in human cancer, implying that neither loss of
      CDKN3 activity nor constitutive gain of CDKN3 expression offer an advantage to
      tumorigenesis. Recently, it was found that CDKN3 transcript and protein levels
      fluctuate during the cell cycle, peaking in mitosis. Given that rapidly growing
      tumors have more mitotic cells, the high level of mitotic CDKN3 expression is the
      most plausible mechanism of frequent CDKN3 overexpression in human cancer. This
      finding clarifies the mechanism of CDKN3 overexpression in human cancer and
      questions the view of CDKN3 as a tumor suppressor.

PMID- 28504192
TI  - Correlates of protection for enteric vaccines.
AB  - An immunological Correlate of Protection (CoP) is an immune response that is
      statistically interrelated with protection. Identification of CoPs for enteric
      vaccines would help design studies to improve vaccine performance of licensed
      vaccines in low income settings, and would facilitate the testing of future
      vaccines in development that might be more affordable. CoPs are lacking today for
      most existing and investigational enteric vaccines. In order to share the latest
      information on CoPs for enteric vaccines and to discuss novel approaches to
      correlate mucosal immune responses in humans with protection, the Foundation
      Merieux organized an international conference of experts where potential CoPs for
      vaccines were examined using case-studies for both bacterial and viral enteric
      pathogens. Experts on the panel concluded that to date, all established enteric
      vaccine CoPs, such as those for hepatitis A, Vi typhoid and poliovirus vaccines,
      are based on serological immune responses even though these may poorly reflect
      the relevant gut immune responses or predict protective efficacy. Known CoPs for
      cholera, norovirus and rotavirus could be considered as acceptable for
      comparisons of similarly composed vaccines while more work is still needed to
      establish CoPs for the remaining enteric pathogens and their candidate vaccines.
      Novel approaches to correlate human mucosal immune responses with protection
      include the investigation of gut-originating antibody-secreting cells (ASCs), B
      memory cells and follicular helper T cells from samples of peripheral blood
      during their recirculation.

PMID- 28504193
TI  - Global economic evaluations of rotavirus vaccines: A systematic review.
AB  - INTRODUCTION: World Health Organization (WHO) recommends Rotavirus vaccines to
      prevent and control rotavirus infections. Economic evaluations (EE) have been
      considered to support decision making of national policy. Summarizing global
      experience of the economic value of rotavirus vaccines is crucial in order to
      encourage global WHO recommendations for vaccine uptake. Therefore, a systematic
      review of economic evaluations of rotavirus vaccine was conducted. METHODS: We
      searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI
      Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full
      economic evaluations studies, published from inception to November 2015,
      evaluating Rotavirus vaccines preventing Rotavirus infections were included. The
      methods, assumptions, results and conclusions of the included studies were
      extracted and appraised using WHO guide for standardization of EE of immunization
      programs. RESULTS: 104 relevant studies were included. The majority of studies
      were conducted in high-income countries. Cost-utility analysis was mostly
      reported in many studies using incremental cost-effectiveness ratio per DALY
      averted or QALY gained. Incremental cost per QALY gained was used in many studies
      from high-income countries. Mass routine vaccination against rotavirus provided
      the ICERs ranging from cost-saving to highly cost-effective in comparison to no
      vaccination among low-income countries. Among middle-income countries,
      vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to
      low- or no subsidized price of rotavirus vaccines from external funders, being
      not cost-effective was reported in some high-income settings. CONCLUSION: Mass
      vaccination against rotavirus was generally found to be cost-effective,
      particularly in low- and middle-income settings according to the external
      subsidization of vaccine price. On the other hand, it may not be a cost-effective
      intervention at market price in some high-income settings. This systematic review
      provides supporting information to health policy-makers and health professionals
      when considering rotavirus vaccination as a national program.

PMID- 28504191
TI  - Lethal factor antibodies contribute to lethal toxin neutralization in recipients
      of anthrax vaccine precipitated.
AB  - A major difference between two currently licensed anthrax vaccines is presence
      (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States
      Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT)
      component Lethal Factor (LF). The primary immunogen in both vaccine formulations
      is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an
      accepted correlate of vaccine efficacy; however, vaccination studies in animal
      models have demonstrated that LF antibodies can be protective. In this report we
      compared humoral immune responses in cohorts of AVP (n=39) and AVA recipients
      (n=78) matched 1:2 for number of vaccinations and time post-vaccination, and
      evaluated whether the LF response contributes to LT neutralization in human
      recipients of AVP. PA response rates (>=95%) and PA IgG concentrations were
      similar in both groups; however, AVP recipients exhibited higher LT
      neutralization ED50 values (AVP: 1464.0+/-214.7, AVA: 544.9+/-83.2, p<0.0001) and
      had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees
      (1%). Multiple regression analysis revealed that LF IgG makes an independent and
      additive contribution to the LT neutralization response in the AVP group.
      Affinity purified LF antibodies from two independent AVP recipients neutralized
      LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT
      neutralization. This study documents the benefit of including an LF component to
      PA-based anthrax vaccines.

PMID- 28504195
TI  - FGF18 protects against 6-hydroxydopamine-induced nigrostriatal damage in a rat
      model of Parkinson's disease.
AB  - Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological
      hallmark of Parkinson's disease (PD). However, the underlying mechanism of this
      injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in
      midbrain development and has been reported to protect neurons from ischemic
      injury, we investigated whether FGF18 exerted a protective effect on dopaminergic
      neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the
      neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3beta signaling
      pathway. Further study of the 6-OHDA-induced PD rat model indicated that FGF18
      improved the behavioral dysfunction in PD rats and reduced the tyrosine
      hydroxylase (TH)-positive neuronal loss in the SN. In addition, 6-OHDA induced a
      loss of TH-positive fibers that was reversed by pretreatment with FGF18. Taken
      together, these data suggest that FGF18 plays a protective role against
      parkinsonian neurodegeneration in the nigrostriatal system in a 6-OHDA-induced PD
      rat model and that further drug discovery based on FGF18 has a potential role for
      PD therapy.

PMID- 28504196
TI  - Human subthalamic nucleus - Automatic auditory change detection as a basis for
      action selection.
AB  - The subthalamic nucleus (STN) shapes motor behavior and is important for the
      initiation and termination of movements. Here we ask whether the STN takes
      aggregated sensory information into account, in order to exert this function. To
      this end, local field potentials (LFP) were recorded in eight patients suffering
      from Parkinson's disease and receiving deep-brain stimulation of the STN
      bilaterally. Bipolar recordings were obtained postoperatively from the
      externalized electrode leads. Patients were passively exposed to trains of
      auditory stimuli containing global deviants, local deviants or combined
      global/local deviants. The surface event-related potentials of the Parkinson's
      patients as well as those of 19 age-matched healthy controls were characterized
      by a mismatch negativity (MMN) that was most pronounced for the global/local
      double deviants and less prominent for the other deviant conditions. The left and
      right STN LFPs similarly were modulated by stimulus deviance starting at about
      100ms post-stimulus onset. The MMN has been viewed as an index of an automatic
      auditory change detection system, more recently phrased in terms of predictive
      coding theory, which prepares the organism for attention shifts and for action.
      The LFP-data from the STN clearly demonstrate that the STN receives information
      on stimulus deviance, possibly as a means to bias the system to interrupt ongoing
      and to allow alternative actions.

PMID- 28504194
TI  - Vaccination with recombinant paramyosin in Montanide ISA206 protects against
      Schistosoma japonicum infection in water buffalo.
AB  - BACKGROUND: Schistosomiasis japonica is a zoonosis and presents significant
      public health problems in China and the Philippines. Vaccines targeting domestic
      animals constitute attractive control measures. METHODS: We conducted three
      vaccine trials to evaluate the protective efficacy of recombinant full-length
      paramyosin (rSj97) in water buffalo. Animals were immunized with 3 doses of rSj97
      adjuvanted with ISA206 at 250MUg/dose or 500MUg/dose at 4wk intervals before
      challenge with 1000 Schistosoma japonicum cercariae. The primary outcome was worm
      burden assessed by portal perfusion 8-10weeks post challenge. Safety measures
      included weight, temperature, body condition score, hemogram and routine assays
      for hepatic and renal function. RESULTS: The three-dose regimen was well
      tolerated in all three trials. In the first trial, vaccinated buffalo had 51.5%
      lower worm burden post challenge compared to controls. In the second trial,
      buffalo immunized with 500MUg/dose of rSj97 had 57.8% lower worm burden compared
      to controls (p=0.026). A similar but not significant reduction (60.9%) was
      observed with animals administered with 250ug rSj97/dose. In the third trial,
      buffalo immunized with a 500MUg/dose of rSj97 had 57.8% lower worm burden
      compared to controls (p=0.014). CONCLUSIONS: These findings indicated that rSj97
      is a safe and promising vaccine candidate for schistosomiasis japonica in water
      buffalo.

PMID- 28504197
TI  - Intravenous injection of umbilical cord-derived mesenchymal stromal cells
      attenuates reactive gliosis and hypomyelination in a neonatal intraventricular
      hemorrhage model.
AB  - Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns,
      resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic
      encephalopathy and periventricular leukomalacia. In this study, we investigated
      the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal
      stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical
      application. UC-MSCs were cultured with alphaMEM medium supplemented with FBS or
      RM. A neonatal IVH mouse model at postnatal day 5 was generated by
      intraventricular injection of autologous blood, and mice were intravenously
      administered 1*105 UC-MSCs two days after IVH. Brain magnetic resonance imaging
      was performed at postnatal day 15, 22 and neurological behavioral measurements
      were performed at postnatal day 23, accompanied by histopathological analysis and
      cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs
      cultured with alphaMEM and RM met the criteria of MSCs and improved behavioral
      outcome of IVH mice. Moreover the RM group exhibited significant behavioral
      improvement compared to the control group. Histopathological analysis revealed UC
      MSCs cultured with RM significantly attenuated periventricular reactive gliosis,
      hypomyelination, and periventricular cell death observed after IVH. Furthermore,
      human brain-derived neurotrophic factor and hepatocyte growth factor were
      elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model
      mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate
      neonatal IVH by protecting gliosis and apoptosis of the injured brain, and
      intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH
      in clinic.

PMID- 28504198
TI  - Rapamycin suppresses Abeta25-35- or LPS-induced neuronal inflammation via
      modulation of NF-kappaB signaling.
AB  - Rapamycin (RAPA), an inhibitor of mammalian target of rapamycin (mTOR), exhibits
      a high neuroprotective action against neurodegenerative diseases in mouse models.
      Since neuroinflammation has been shown to be involved in Alzheimer's disease (AD)
      development and progression, the aim of this study was to examine the anti
      inflammatory role of RAPA in AD in vivo and in vitro, and investigate the
      underlying mechanisms. We found that amyloid-beta (Abeta) induced neuronal
      inflammation and a remarkable increase in mTOR activity in in-vivo and in-vitro
      models of inflammation, suggesting the critical role of mTOR signaling in
      neuronal inflammation. In addition, administration of RAPA was found to down
      regulate mTOR, p-mTOR, Nuclear factor kappa B (NF-kappaB) p65, p-p65, TNF-alpha,
      IL-1beta and Bax protein expression in Abeta25-35- or lipopolysaccharides (LPS)
      treated mice and cultured Neuro-2a (N2a) cells. Moreover, RAPA disrupted Abeta25
      35-induced nuclear translocation of mTOR and NF-kappaB. Our findings indicate
      that RAPA inhibits Abeta25-35- or LPS-induced neuronal inflammation through
      suppressing mTOR signaling and reducing nuclear import of NF-kappaB.

PMID- 28504199
TI  - Lithopedion developed in a non-communicating rudimentary uterine horn: CT
      features.

PMID- 28504200
TI  - Portal invasion: An exceptional complication of hepatic hydatid disease.

PMID- 28504201
TI  - Cilia - The sensory antennae in the eye.
AB  - Cilia are hair-like projections found on almost all cells in the human body.
      Originally believed to function merely in motility, the function of solitary non
      motile (primary) cilia was long overlooked. Recent research has demonstrated that
      primary cilia function as signalling hubs that sense environmental cues and are
      pivotal for organ development and function, tissue hoemoestasis, and maintenance
      of human health. Cilia share a common anatomy and their diverse functional
      features are achieved by evolutionarily conserved functional modules, organized
      into sub-compartments. Defects in these functional modules are responsible for a
      rapidly growing list of human diseases collectively termed ciliopathies. Ocular
      pathogenesis is common in virtually all classes of syndromic ciliopathies, and
      disruptions in cilia genes have been found to be causative in a growing number of
      non-syndromic retinal dystrophies. This review will address what is currently
      known about cilia contribution to visual function. We will focus on the molecular
      and cellular functions of ciliary proteins and their role in the photoreceptor
      sensory cilia and their visual phenotypes. We also highlight other ciliated cell
      types in tissues of the eye (e.g. lens, RPE and Muller glia cells) discussing
      their possible contribution to disease progression. Progress in basic research on
      the cilia function in the eye is paving the way for therapeutic options for
      retinal ciliopathies. In the final section we describe the latest advancements in
      gene therapy, read-through of non-sense mutations and stem cell therapy, all
      being adopted to treat cilia dysfunction in the retina.

PMID- 28504202
TI  - Corrigendum to "The rod-driven a-wave of the dark-adapted mammalian
      electroretinogram" [Progress in Retinal and Eye Research, volume 39, March 2014,
      pages 1-22].

PMID- 28504203
TI  - Internal validation of STRmixTM for the interpretation of single source and mixed
      DNA profiles.
AB  - The interpretation of DNA evidence can entail analysis of challenging STR typing
      results. Genotypes inferred from low quality or quantity specimens, or mixed DNA
      samples originating from multiple contributors, can result in weak or
      inconclusive match probabilities when a binary interpretation method and
      necessary thresholds (such as a stochastic threshold) are employed. Probabilistic
      genotyping approaches, such as fully continuous methods that incorporate
      empirically determined biological parameter models, enable usage of more of the
      profile information and reduce subjectivity in interpretation. As a result,
      software-based probabilistic analyses tend to produce more consistent and more
      informative results regarding potential contributors to DNA evidence. Studies to
      assess and internally validate the probabilistic genotyping software STRmixTM for
      casework usage at the Federal Bureau of Investigation Laboratory were conducted
      using lab-specific parameters and more than 300 single-source and mixed
      contributor profiles. Simulated forensic specimens, including constructed
      mixtures that included DNA from two to five donors across a broad range of
      template amounts and contributor proportions, were used to examine the
      sensitivity and specificity of the system via more than 60,000 tests comparing
      hundreds of known contributors and non-contributors to the specimens. Conditioned
      analyses, concurrent interpretation of amplification replicates, and application
      of an incorrect contributor number were also performed to further investigate
      software performance and probe the limitations of the system. In addition, the
      results from manual and probabilistic interpretation of both prepared and
      evidentiary mixtures were compared. The findings support that STRmixTM is
      sufficiently robust for implementation in forensic laboratories, offering
      numerous advantages over historical methods of DNA profile analysis and greater
      statistical power for the estimation of evidentiary weight, and can be used
      reliably in human identification testing. With few exceptions, likelihood ratio
      results reflected intuitively correct estimates of the weight of the genotype
      possibilities and known contributor genotypes. This comprehensive evaluation
      provides a model in accordance with SWGDAM recommendations for internal
      validation of a probabilistic genotyping system for DNA evidence interpretation.

PMID- 28504204
TI  - Elastic staining-a rejuvenated method to reassess prognosis and serosal invasion
      in patients with pT3N0M0 gastric cancer.
AB  - Prognosis of pT3N0M0 gastric cancer (GC) varies greatly, though the major factor
      conferring poor prognosis is unclear. Subserosal elastic lamina invasion (ELI+)
      is closely associated with poor outcomes in pT3 colorectal cancer, but related
      research on GC is unavailable. This study aimed to identify the influence of ELI+
      on the prognosis of patients with pT3N0M0 GC and its relationship with serosal
      invasion using elastic staining. We retrospectively reviewed 94 and 28 patients
      with pT3N0M0 and pT4aN0M0 GC who underwent gastrectomy between 1994 and 2005. For
      the former, one section with invasion depth closest to the peritoneal surface and
      one corresponding paraffin block for each specimen were selected for conventional
      elastic staining to assess the relationship between ELI+ and patients' clinical
      characteristics and survival. pT3N0M0 GC specimens were divided into 3 groups
      based on staining results: ELI+ (N=51), non-invasion (N=31), and unidentified
      (N=12). ELI+ was closely related to recurrence and lymphovascular invasion. Five
      year disease-free (DFS) (46%) and overall (OS) (36%) survival rates were
      significantly lower in the ELI+ than in the non-invasion or unidentified groups
      (P<.0001); no obvious difference was found between the ELI+ and pT4aN0M0 groups
      (P=.25). Multivariate analysis showed ELI+ and recurrence as independent
      prognostic factors for DFS in pT3 GC patients. In conclusion, elastic staining is
      an effective and highly feasible method for predicting prognosis and evaluating
      the serosal invasion depth of pT3 GC. pT3 GC accompanied with ELI+ is an obvious
      adverse prognostic factor and could be considered a treatment for pT4a GC.

PMID- 28504206
TI  - BRAF V600E mutation in pediatric intracranial and cranial juvenile
      xanthogranuloma.
AB  - Juvenile xanthogranuloma (JXG) is a cutaneous form of non-Langerhans cell
      histiocytosis, primarily affecting children. The lesion is presumed to originate
      from either macrophages or dermal dendritic cells. JXG can rarely present as an
      isolated intracranial lesion and, in contrast to the dismal outcome of patients
      with systemic disease, cranial JXG has been shown to carry a more favorable
      prognosis. Here, we report for the first time 3 pediatric cases of JXG with a
      BRAF V600E mutation, 2 with intracranial lesions and 1 with cranial lesions.
      Although these intracranial/cranial lesions have been referred to as JXG, they
      likely differ from cutaneous JXG in both the clinical features and BRAF status.
      It may be more appropriate to classify intracranial/cranial JXG in the same group
      as Langerhans cell histiocytosis and Erdheim-Chester disease, which also have a
      BRAF V600E mutation. Further study of BRAF status in a larger series of JXG is
      warranted.

PMID- 28504205
TI  - Comparison of clinicopathologic characteristics of gastric follicular lymphomas
      and duodenal follicular lymphomas.
AB  - We compared the incidence, esophagogastroduodenoscopy (EGD) findings, and
      histopathologic characteristics of gastric and duodenal follicular lymphomas
      (FL). Of 626 FL cases, primary gastric FL and secondary gastric involvement of FL
      were observed in 1% and 5% of the cases, respectively, which were lower
      incidences than duodenal FL (10% and 9%, respectively). Gastric FL usually
      appeared as submucosal tumors (primary, 71%; secondary, 79%), whereas duodenal
      FL, as granular lesions (primary, 92%: secondary, 87%). In the granular duodenal
      lesions, the neoplastic follicles were located sparsely on the muscularis mucosa
      and could be found between villi, whereas in the stomach, similar lesions were
      hidden within the lamina propria, and only larger lesions such as submucosal
      tumors could be detected on the mucosal surface. The differences in the
      incidences and EGD findings were considered to be associated with structural
      differences of the lamina propria. Typical FL features: grades 1-2 histology,
      follicularity, and CD10+ and/or BCL6+ and BCL2+ were usually observed in all
      primary and secondary gastric and duodenal FL. Gastroduodenal and bone marrow
      involvement were found in 12% and 33% of the cases, respectively, and there was
      no significant correlation between them (P=.095). Twenty-nine cases (5%) were up
      staged by gastroduodenal-positive results. In conclusion, the histopathology of
      gastric FL was similar to that of duodenal and nodal FL; the differences in the
      incidence and EGD findings between gastric and duodenal FL were considered to be
      associated with structural difference of the lamina propria, and EGD was useful
      as a staging procedure.

PMID- 28504207
TI  - A novel fusion of HNRNPA1-ALK in inflammatory myofibroblastic tumor of urinary
      bladder.
AB  - Here, we report an inflammatory myofibroblastic tumor (IMT) of the urinary
      bladder with a novel HNRNPA1-ALK fusion. To the best of our knowledge, this is
      the first case of a tumor with HNRNPA1-ALK fusion. A 42-year-old Japanese man
      underwent total cystectomy because of an invasive urinary bladder tumor. Grossly,
      the tumor had invaded the peribladder fat tissue. Histologically, it comprised
      spindle neoplastic cells with intermingled inflammatory cells.
      Immunohistochemically, it was positive for ALK, SMA, desmin, cytokeratin, and
      vimentin, consistent with the immunohistochemical characteristics of IMTs.
      Fluorescence in situ hybridization demonstrated an ALK split, and the presence of
      HNRNPA1-ALK was revealed by RNA sequencing. We identified a novel transcript
      fusion of exon 2 of HNRNPA1 and exon 18 of ALK, resulting in ALK protein
      overexpression. These findings provide useful information on the biology and
      tumorigenesis of IMTs, thus facilitating the development of molecular-targeted
      therapeutics.

PMID- 28504208
TI  - PTEN loss and p27 loss differ among morphologic patterns of prostate cancer,
      including cribriform.
AB  - The presence and extent of cribriform pattern of prostate cancer portend
      recurrence and cancer death. The relative expressions within this morphology of
      the prognostically adverse loss of PTEN, and the downstream inactivation of cell
      cycle inhibitor p27/Kip1 had been uncertain. In this study, we examined 52 cases
      of cribriform cancer by immunohistochemistry for PTEN, p27, and CD44 variant
      (v)7/8, and a subset of 17 cases by chromogenic in situ hybridization (ISH) using
      probes for PTEN or CDKN1B (gene for p27). The fractions of epithelial pixels
      positive by immunohistochemistry and ISH were digitally assessed for benign
      acini, high-grade prostatic intraepithelial neoplasia, and 8 morphologic patterns
      of cancer. Immunostaining results demonstrated that (1) PTEN loss was significant
      for fused small acini, cribriform-central cells, small cribriform acini, and
      Gleason grade 5 cells in comparison with other acini; (2) p27 loss was
      significant only for cribriform-peripheral cells and borderline significant for
      fused small acini in comparison with benign acini; and (3) CD44v7/8 showed
      expression loss in cribriform-peripheral cells; other comparisons were not
      significant. ISH showed that cribriform cancer had significant PTEN loss
      normalized to benign acini (P<.02), whereas Gleason 3 cancer or fused small acini
      did not. With CDKN1B, the degree of signal loss among various cancer morphologies
      was insignificant. In conclusion, molecular disparities emerged between the fused
      small acini and cribriform patterns of Gleason 4 cancer. PTEN or p27 loss as
      prognostic factors demands distinct assessment in the varieties of Gleason 4
      cancer, and in the biphenotypic peripheral versus central populations in
      cribriform structures.

PMID- 28504209
TI  - An online readability analysis of pathology-related patient education articles:
      an opportunity for pathologists to educate patients.
AB  - Information for patients regarding their clinical conditions and treatment
      options is widely available online. The American Medical Association and National
      Institutes of Health recommend that online patient-oriented materials be written
      at no higher than a seventh-grade reading level to ensure full comprehension by
      the average American. This study sought to determine whether online patient
      oriented materials explaining common pathology procedures are written at
      appropriate reading levels. Ten pathology procedures that patients would likely
      research were queried into Google search, and plain text from the first 10 Web
      sites containing patient education materials for each procedure was analyzed
      using 10 validated readability scales. We determined mean reading levels of
      materials grouped by readability scale, procedure, and Web site domain, the
      overall average reading level of all resources, and popular Web site domains. One
      hundred Web sites were accessed; one was omitted for short length (<100 words).
      The average reading grade level of the 99 materials, none of which met national
      health literacy guidelines (range, 7.3-17.4), was 10.9. Twenty-nine articles
      (29%) required a high school education for full comprehension, and 4 (4%)
      required an undergraduate college education. Most frequently accessed Web site
      domains included medlineplus.gov, webmd.com (both accessed 7 times), and
      labtestsonline.org (accessed 6 times). Average reading levels of the 11 most
      commonly accessed Web sites ranged from 8.25 (patient.info) to 12.25
      (mayoclinic.org). Readability levels of most online pathology-related patient
      education materials exceeded those recommended by national health literacy
      guidelines. These patient education materials should be revised to help patients
      fully understand them.

PMID- 28504210
TI  - Arachidonic acid is important for efficient use of light by the microalga
      Lobosphaera incisa under chilling stress.
AB  - The oleaginous microalga Lobosphaera incisa (Trebouxiophyceae, Chlorophyta)
      contains arachidonic acid (ARA, 20:4 n-6) in all membrane glycerolipids and in
      the storage lipid triacylglycerol. The optimal growth temperature of the wild
      type (WT) strain is 25 degrees C; chilling temperatures (<=15 degrees C) slow its
      growth. This effect is more pronounced in the delta-5-desaturase ARA-deficient
      mutant P127, in which ARA is replaced with dihomo-gamma-linolenic acid (DGLA,
      20:3 n-6). In nutrient-replete cells grown at 25 degrees C, the major chloroplast
      lipid monogalactosylglycerol (MGDG) was dominated by C18/C16 species in both
      strains. Yet ARA constituted over 10% of the total fatty acids in the WT MGDG as
      a component of C20/C18 and C20/C20 species, whereas DGLA was only a minor
      component of MGDG in P127. Both strains increased the percentage of 18:3 n-3 in
      membrane lipids under chilling temperatures. The temperature downshift led to a
      dramatic increase in triacylglycerol at the expense of chloroplast lipids. WT and
      P127 showed a similarly high photochemical quantum yield of photosystem II,
      whereas non-photochemical quenching (NPQ) and violaxanthin de-epoxidation were
      drastically higher in P127, especially at 15 degrees C. Fluorescence anisotropy
      measurements indicated that ARA-containing MGDG might contribute to sustaining
      chloroplast membrane fluidity upon dropping to the chilling temperature. We
      hypothesize that conformational changes in chloroplast membranes and increased
      rigidity of the ARA-deficient MGDG of P127 at chilling temperatures are not
      compensated by trienoic fatty acids. This might 'lock' violaxanthin de-epoxidase
      in the activated state causing high constitutive NPQ and alleviate the risk of
      photodamage under chilling conditions in the mutant.

PMID- 28504211
TI  - Ectopic adenine nucleotide translocase activity controls extracellular ADP levels
      and regulates the F1-ATPase-mediated HDL endocytosis pathway on hepatocytes.
AB  - Ecto-F1-ATPase is a complex related to mitochondrial ATP synthase which has been
      identified as a plasma membrane receptor for apolipoprotein A-I (apoA-I), the
      major protein of high-density lipoprotein (HDL), and has been shown to contribute
      to HDL endocytosis in several cell types. On hepatocytes, apoA-I binding to ecto
      F1-ATPase stimulates extracellular ATP hydrolysis into ADP, which subsequently
      activates a P2Y13-mediated HDL endocytosis pathway. Interestingly, other
      mitochondrial proteins have been found to be expressed at the plasma membrane of
      several cell types. Among these, adenine nucleotide translocase (ANT) is an
      ADP/ATP carrier but its role in controlling extracellular ADP levels and F1
      ATPase-mediated HDL endocytosis has never been investigated. Here we confirmed
      the presence of ANT at the plasma membrane of human hepatocytes. We then showed
      that ecto-ANT activity increases or reduces extracellular ADP level, depending on
      the extracellular ADP/ATP ratio. Interestingly, ecto-ANT co-localized with ecto
      F1-ATPase at the hepatocyte plasma membrane and pharmacological inhibition of
      ecto-ANT activity increased extracellular ADP level when ecto-F1-ATPase was
      activated by apoA-I. This increase in the bioavailability of extracellular ADP
      accordingly translated into an increase of HDL endocytosis on human hepatocytes.
      This study thus uncovered a new location and function of ANT for which activity
      at the cell surface of hepatocytes modulates the concentration of extracellular
      ADP and regulates HDL endocytosis.

PMID- 28504213
TI  - What is it to become an octogenarian 40 years after the first angioplasty?

PMID- 28504214
TI  - His master's art, Andreas Gruntzig's approach to performing and teaching coronary
      angioplasty.

PMID- 28504215
TI  - Commemorating the 15-year anniversary of TAVI: insights into the early stages of
      development, from concept to human application, and perspectives.

PMID- 28504212
TI  - Psychological Adjustment of Parents of Children Born with Atypical Genitalia 1
      Year after Genitoplasty.
AB  - PURPOSE: We examined the psychological adjustment of parents of children born
      with moderate to severe genital atypia 12 months after their child underwent
      genitoplasty. MATERIALS AND METHODS: Parents were recruited longitudinally from a
      multicenter collaboration of 10 pediatric hospitals with specialty care for
      children with disorders/differences of sex development and/or congenital adrenal
      hyperplasia. Parents completed measures of depressive and anxious symptoms,
      illness uncertainty, quality of life, posttraumatic stress and decisional regret.
      RESULTS: Compared to levels of distress at baseline (before genitoplasty) and 6
      months after genitoplasty, data from 25 mothers and 20 fathers indicated
      significant improvements in all psychological distress variables. However, a
      subset of parents continued endorsing clinically relevant distress. Some level of
      decisional regret was endorsed by 28% of parents, although the specific decision
      that caused regret was not specified. CONCLUSIONS: Overall the majority of
      parents were coping well 1 year after their child underwent genitoplasty. Level
      of decisional regret was related to having a bachelor's level of education,
      increased levels of illness uncertainty preoperatively and persistent illness
      uncertainty at 12 months after genitoplasty but was unrelated to postoperative
      complications.

PMID- 28504216
TI  - Interventional cardiology's golden age of publishing.

PMID- 28504219
TI  - One-year clinical results of the Italian diffuse/multivessel disease ABSORB
      prospective registry (IT-DISAPPEARS).
AB  - AIMS: The present multicentre prospective study, IT-DISAPPEARS, was designed with
      the aim of evaluating early and long-term clinical outcomes of the Absorb BVS in
      patients with long coronary lesions and/or multivessel coronary artery disease.
      The aim of this article is to present the one-year clinical results of this
      study. METHODS AND RESULTS: Between November 2014 and January 2016, we enrolled
      1,002 patients undergoing BVS implantation (long lesion [>= 24 mm] of a single
      vessel in 80.4%, at least two BVS in two or three coronary vessels in 8.6% and
      both criteria in 11%). Clinical presentation was an acute coronary syndrome in
      59.8% of patients, including ST-elevation myocardial infarction in 21.8%. The
      primary endpoint was the device-oriented composite endpoint (DOCE) of cardiac
      death, target vessel MI, and ischaemia-driven TLR at one year. We implanted 2,040
      BVS according to a pre-specified technique. One-year follow-up was available in
      956 patients (95.4%). The rate of DOCE was 9.9% (95 patients). Cardiac death
      occurred in five patients (0.5%), while target vessel MI and TLR each occurred in
      45 (4.7%) patients. The one-year rates of all-cause death, non-fatal MI, and any
      revascularisation were 1.2%, 5.4%, and 10.9%, respectively. The rate of
      definite/probable scaffold thrombosis was 0.9%. CONCLUSIONS: This is the first
      study specifically investigating the Absorb technology in patients with a high
      atherosclerotic burden and multivessel disease. The mandatory adherence to a pre
      specified implantation technique led to minimising the risk of device failure
      reported by other studies, in particular with respect to the rate of DOCE and
      scaffold thrombosis.

PMID- 28504218
TI  - First-in-human evaluation of a novel poly-L-lactide based sirolimus-eluting
      bioresorbable vascular scaffold for the treatment of de novo native coronary
      artery lesions: MeRes-1 trial.
AB  - AIMS: The MeRes-1 trial sought to study the safety and effectiveness of a novel
      sirolimus-eluting bioresorbable vascular scaffold (MeRes100 BRS) in treating de
      novo native coronary artery lesions by clinical evaluation and using multiple
      imaging modalities. METHODS AND RESULTS: The MeRes-1 first-in-human trial was a
      single-arm, prospective, multicentre study, which enrolled 108 patients with de
      novo coronary artery lesions (116 scaffolds were deployed to treat 116 lesions in
      108 patients). At six months, quantitative coronary angiography revealed in
      scaffold late lumen loss of 0.15+/-0.23 mm with 0% binary restenosis. Optical
      coherence tomography demonstrated minimum scaffold area (6.86+/-1.73 mm2) and
      percentage neointimal strut coverage (99.30%). Quantitative intravascular
      ultrasound analysis confirmed a 0.14+/-0.16 mm2 neointimal hyperplasia area. At
      one year, major adverse cardiac events, a composite of cardiac death, any
      myocardial infarction and ischaemia-driven target lesion revascularisation,
      occurred in only one patient (0.93%) and there was no scaffold thrombosis
      reported. At one year, computed tomography angiography demonstrated that all
      scaffolds were patent and in-scaffold mean percentage area stenosis was 11.33+/
      26.57%. CONCLUSIONS: The MeRes-1 trial demonstrated the safety and effectiveness
      of MeRes100 BRS. The favourable clinical outcomes and effective vascular
      responses have provided the basis for further studies in a larger patient
      population. The MeRes-1 trial is registered at the Clinical Trials Registry
      India.

PMID- 28504220
TI  - EAPCI registries: a first step towards systematic monitoring of European
      interventional cardiology practice.

PMID- 28504221
TI  - Current trends in coronary interventions: an overview from the EAPCI registries.

PMID- 28504222
TI  - Current trends in structural heart interventions: an overview of the EAPCI
      registries.

PMID- 28504223
TI  - Belgium: coronary and structural heart interventions from 2010 to 2015.
AB  - In a ranking of the gross domestic product per capita in 2015, Belgium ranked
      19th in the world according to the International Monetary Fun1d and the World
      Bank. It has a Human Development Index of 0.890, in which it is preceded by only
      20 other countries in the world. This is, at least in part, due to a well
      developed social security system on which all citizens can rely. Over the last 5
      10 years, however, this system has come under increasing pressure. This has
      resulted in insufficient, incomplete and late reimbursement of all technologies
      that were introduced over the last ten years in the cathlab: intracoronary
      imaging techniques are not reimbursed at all, and FFR only to a vastly
      insufficient degree. For several structural heart interventions, a system of
      limited and incomplete reimbursement has recently been set up, with a requirement
      to organise these procedures within the frames of hospital networks. Numbers of
      PCIs have risen by 15% over the last four years, coinciding with an increase in
      the number of cathlabs by 50%, aiming at better access to primary PCI for STEMI
      patients. This has also resulted in a decrease in the average procedure volume
      per centre. Two thirds of PCIs are performed via the radial access. DES
      penetration has increased to 74%, approaching 100% in some centres, while the
      uptake of BRS has been very limited so far.

PMID- 28504224
TI  - Denmark: coronary and structural heart interventions from 2010 to 2015.
AB  - Interventional cardiology in Denmark has been carried out since the mid 1980s.
      Interventional cardiology is only performed at a few high-volume centres.
      Healthcare coverage is universal and is essentially free of charge. Hospitals are
      mostly publicly owned and financed by fixed budgets and, in part, an activity
      based funding system. Approximately 30,000 coronary angiographies (CAG), 10,000
      percutaneous coronary interventions (PCIs) of which approximately 25% are primary
      PCIs, and 500 transcatheter aortic valve implantations (TAVIs) are carried out
      each year. The numbers of CAG and PCI have reached a plateau in recent years,
      whereas structural heart interventions, in particular TAVI, are increasing.
      Around 90% of all patients treated with PCI have a stent implanted, with more
      than 95% of these being drug-eluting stents. There is a low but increasing use of
      bioabsorbable scaffolds and drug-eluting balloons.

PMID- 28504225
TI  - Egypt: coronary and structural heart interventions from 2010 to 2015.
AB  - Interventional cardiology procedures are constantly increasing in numbers and in
      quality, especially in developing countries such as Egypt. The numbers and types
      of procedure now available have driven development in the field and in its
      accompanying services. The aim of this short report is to present a review of the
      development of interventional cardiology in Egypt during the period 2010-2015 and
      the demographic, economic and educational factors that have affected this
      process. We collected and analysed data provided by different centres and from
      the distributors of intervention tools for the years 2010 to 2015. Analysis of
      these data showed a steady growth of primary PCI, amounting to a threefold
      increase over the six-year period. There are increasing numbers of PCI-capable
      centres, especially in Cairo. Almost 55,000 PCIs are performed yearly in Egypt
      utilising around 100,000 stents; the percentage of drug-eluting stents (DES) used
      has increased to 65-70% (90% in private and insured patients). Structural
      intervention is growing fast for congenital heart disease, and balloon mitral
      valvuloplasty has become the default strategy. The numbers of TAVI and EVAR are
      also increasing, although cost remains the greatest challenge. These changes can
      be attributed to the increasing numbers of ischaemic heart disease patients over
      the last 25 years, involving improved education and awareness, patients
      presenting at a younger age, and improved practice in intervention. In Egypt,
      there has been a steady growth in PCI and intervention tools which has been
      faster in coronary and congenital heart disease than in structural heart disease
      during the period from 2010 to 2015.

PMID- 28504226
TI  - France: coronary and structural heart interventions from 2010 to 2015.
AB  - France, with its 66 million inhabitants, has a long tradition in interventional
      cardiology, with numerous innovations and contributions to the dynamism of
      European activity. The development of interventional cardiology requires
      supervised training, organisation and participation in studies. This also
      translates into an ever-expanding clinical activity since 2010, such as the
      coronary and structural interventions that are detailed in the present review.

PMID- 28504227
TI  - Israel: coronary and structural heart interventions from 2010 to 2015.
AB  - The Israel Heart Society is a member of the European Society of Cardiology, and
      the Israeli Working Group of Interventional Cardiology is an active participant
      in EAPCI. The aim of this manuscript is to provide a snapshot of cardiac
      interventions performed in the State of Israel during the period 2010-2015. Data
      for this manuscript were collected via collaboration with the National Diseases
      Registries Unit of the Israel Center for Disease Control. During the survey
      period, the Israeli population increased by 7% but only one additional hospital
      with an active cardiac catheterisation laboratory was opened. The vast majority
      of the percutaneous procedures are performed in public hospital settings. Total
      coronary angiography procedures remained stable throughout the survey period, and
      the percentage of PCI out of total coronary angiography procedures remained
      approximately 50% throughout the survey period. More than 90% of the PCI
      procedures were performed using stent deployment, and the use of drug-eluting
      stents increased significantly during the survey period from 46% in 2010 to 92%
      in 2015. The number of TAVI procedures increased dramatically, by more than
      sixfold, from 130 procedures in 2010 to 851 procedures in 2015 (with 130
      implants/million population at Q4 of 2015). The vast majority of interventional
      cardiology procedures are funded by the governmental healthcare providers, and
      all the citizens of the country have access to the most advanced cardiac
      interventions. If corrected for the increase in the population, the volumes of
      coronary interventions are decreasing throughout the country. However, structural
      heart disease interventions, and specifically valvular interventions, are growing
      rapidly and this trend is expected to continue in the near future.

PMID- 28504228
TI  - Italy: coronary and structural heart interventions from 2010 to 2015.
AB  - The aim of this report is to analyse trends in Italian cathlab activity between
      2010 and 2015. Data were obtained from the national database of the Italian
      Society of Interventional Cardiology (GISE), which includes 97% of Italian
      cardiac catheterisation laboratories. The number of percutaneous coronary
      interventions (PCI) has remained relatively stable in the past five years. We
      have observed a significant increase in the number of primary PCI (pPCI) from
      471.5 to 557.5 per million inhabitants with a consequent reduction of rescue
      primary PCI/fibrinolysis. One of the possible explanations for this might be the
      extensive networking for primary PCI and the adoption of Stent for Life
      initiatives in five regions. There has been a notably increased use of drug
      eluting stents and, despite the fact that the introduction of bioabsorbable
      vascular scaffolds is recent, there is a slight, progressively positive trend.
      Invasive physiologic evaluation of coronary stenosis has markedly increased.
      Radial artery access has become the default option for PCI and for pPCI. In the
      last five years, TAVI procedures have doubled in number, while MitraClip and
      mitral repair procedures have shown a fivefold increase. Left atrial appendage
      (LAA) occlusion procedures have more than doubled in four years.

PMID- 28504229
TI  - Kazakhstan: coronary and structural heart interventions from 2010 to 2015.
AB  - This paper presents data on the nascence and development of the interventional
      cardiology service in Kazakhstan. It provides details of the structure of the
      Kazakhstan interventional cardiology service, staff training, the number of
      coronary and structural heart interventions for the period of 2010-2015, as well
      as the peculiarities of the capitation payment method. The number of coronary
      interventions is increasing year by year, though the number of intracoronary
      imaging techniques and intracoronary flow/pressure techniques remains inadequate.
      Structural heart interventions are mostly performed at tertiary hospital level,
      with an ever increasing number of transcatheter aortic valve implantation (TAVI)
      procedures.

PMID- 28504230
TI  - Macedonia: coronary and structural heart interventions from 2010 to 2015.
AB  - The aim of this report is to describe invasive cardiology procedural practice in
      Macedonia during the period from 2010 to 2015. Details of all consecutive 39,899
      patients who underwent cardiovascular, peripheral or structural heart procedures
      during the period from 2010 until 2015 were examined. Clinical and procedure
      characteristics, access site, procedural success and complications were analysed.
      The number of coronary angiographies increased from 5,540 in 2010 to 8,550 in
      2015. Transfemoral access (TFA) was present in 4% of coronary angiographies in
      2010 and had decreased to 1% in 2015. The number of primary percutaneous coronary
      interventions (PCI) for acute ST-segment elevation myocardial infarction
      increased from 763 to 1,175 and both chronic total occlusion and left main
      coronary artery interventions also increased over time. In 2015, the drug-eluting
      stent penetration rate was 65%. Structural heart interventions, including
      transcatheter aortic valve implantations (TAVI) were introduced in 2014 and 23
      TAVI cases have since been performed. Transradial access was performed in 38,455
      (96%) of all patients. Wrist access adoption in the majority of cardiovascular
      interventions is possible in all PCI centres in Europe if an appropriate national
      strategy is developed.

PMID- 28504231
TI  - Poland: coronary and structural heart interventions from 2010 to 2015.
AB  - For the last five years, invasive cardiology in Poland has developed extensively.
      Currently, 98% of the 161 Polish cathlabs operate in 24/7 mode, 37 of them
      supported by cardiac surgery departments on-site. A certification curriculum for
      interventional cardiology operators is supported by dedicated workshops and
      scientific meetings during national conferences. The rise in the number of
      coronary angiographies and PCIs was paralleled by an increased use of drug
      eluting stents, bioresorbable vascular scaffolds and physiologic assessment of
      coronary arteries. Radial artery access has become the default option for PCI. A
      rapid adoption of the EAPCI Stent for Life Initiative resulted in a significant
      increase in primary PCIs. Unlike coronary interventions, structural heart
      interventions have evolved unevenly, despite the solid network of Heart Teams set
      up in the 21 most experienced centres. Left atrial appendage closure is offered
      in an increasing number of cathlabs. MitraClip therapy remains largely underused
      (1 procedure/million population/year). Despite the slow growth of TAVI since
      2008, the current annual number of 17.1 TAVI procedures per million population is
      incomparable with countries in Western Europe. A recently introduced EAPCI Valve
      for Life campaign was followed by a 42.6% annual increase in TAVI procedures and
      an improvement in patients' access to therapy in life-saving indications.

PMID- 28504232
TI  - Portugal: coronary and structural heart interventions from 2010 to 2015.
AB  - The aim of the present paper is to report trends in Portuguese interventional
      cardiology from 2010 to 2015. We studied data from the prospective multicentre
      Portuguese National Registry of Interventional Cardiology (RNCI) to analyse
      percutaneous coronary intervention (PCI) procedures and structural heart
      interventions from 2010 to 2015. A total of 73,977 PCIs and 780 transcatheter
      aortic valve implants were performed during the study period. Since 2010 there
      has been a 60% increase in PCI procedures and a twofold increase in primary
      angioplasty rates reaching 316 per million population. Significant PCI trends
      were observed, notably the increase of radial access, a reduction in restenosis
      indications, as well as an increase in stent use, including DES, in imaging and
      in functional techniques. Importantly, there was a fourfold increase in the TAVI
      rates reaching 29 per million population.

PMID- 28504233
TI  - Serbia: coronary and structural heart interventions from 2010 to 2015.
AB  - Serbia's interventional community has been facing the multifaceted challenge of
      an ageing population with cardiovascular diseases as the primary cause of death
      nationwide, coronary artery disease (CAD) being the most prevalent subset. The
      following two fields of activity have marked the trajectory of progress in the
      field of interventional cardiology in Serbia: first, the expansion of the
      infrastructure, mainly through the opening of new catheterisation laboratories
      across all of the country's administrative regions, which has resulted in better
      accessibility to coronary interventions for the general population; second, the
      creation of national platforms for continuous education, training and the
      promotion of clinical research in interventional cardiology, with close
      programmatic links to European Association of Percutaneous Cardiovascular
      Interventions (EAPCI)-based educational initiatives, including the curriculum for
      interventional cardiology. As growth seems to be inherent to the concept of
      progress, we report here on the expanding numbers of coronary interventions in
      the period between January 2010 and December 2015, and the early experiences with
      structural heart interventions in Serbia.

PMID- 28504234
TI  - Spain: coronary and structural heart interventions from 2010 to 2015.
AB  - Since 1990 The Spanish Society of Cardiology Working Group on Cardiac
      Catheterization and Interventional Cardiology has presented a yearly report on
      the data collected in the National Registry, with online support since 2010. The
      Steering Committee has analysed all data provided voluntarily by institutions,
      which consisted of a total of anywhere between 105 and 113 hospitals. Medical
      care was provided to a population of 46.8 million inhabitants in 2015. During
      this period, diagnostic procedures increased progressively from 2010, reaching a
      maximum of 145,836 in 2015, 86% (125,484) corresponding to coronary angiograms.
      This means a ratio of 3,127 diagnostic studies per million inhabitants and 2,746
      coronary angiograms per million inhabitants. Total percutaneous coronary
      interventions have increased to 67,671 procedures, with a ratio of 1,466 per
      million inhabitants where 18,418 were carried out during the acute phase of
      myocardial infarction (21.7%). Radial access has been successfully implemented in
      up to 73.8% of diagnostic procedures and 76.1% of percutaneous interventions.
      Concerning structural interventions such as septal defects, valve interventions
      and closure of left atrial appendage, these have had a marked evolution over
      time, with a total of 1,586 TAVI and 334 LAA closure procedures performed in
      2015.

PMID- 28504235
TI  - Sweden: coronary and structural heart interventions from 2010 to 2015.
AB  - Sparsely populated and with wide non-urbanised areas, Sweden faces specific
      challenges in providing publicly financed, high-quality and equal healthcare to
      all parts of the country. As a result, a decentralised organisation for acute
      coronary care has been developed with coronary care units and catheterisation
      laboratories in several small- and medium-sized city areas. In contrast, highly
      specialised non-emergent interventional procedures are centralised to a few high
      volume centres, mainly located at university hospitals in large city areas.
      Nationwide quality registries with nearly complete coverage facilitate healthcare
      quality improvement and form a basis for clinical research. In this report, we
      present an overview of demographics, healthcare organisation, quality registries
      and procedural data for coronary and structural heart interventions in Sweden
      over the past six years.

PMID- 28504236
TI  - Switzerland: coronary and structural heart interventions from 2010 to 2015.
AB  - In 2015, Switzerland had a population of 8.3 million inhabitants. Since the first
      coronary angioplasty performed by Andreas Gruntzig in Zurich in 1977, the number
      of percutaneous procedures has steadily increased. The aim of this report is to
      summarise the current state of catheter-based cardiac interventions in adults in
      the country and to detail trends between 2010 and 2015. Since 1987, the Working
      Group for Interventional Cardiology of the Swiss Society of Cardiology has
      collected annually aggregate data from all facilities with cardiac
      catheterisation laboratories in the country. In 2015, a total of 37 institutions
      covered 17 of the 26 Swiss cantons. Over the six-year period, there was a
      continuous increase in the number of coronary angiography and percutaneous
      coronary interventions (PCI) (median increase rate of 3.2%/year for coronary
      angiography and of 2.6%/year for PCI). Notable was the adoption of the
      transradial approach for PCI, going from a median rate of 17% in 2012 to 51.9% in
      2015. With respect to structural heart interventions, the number of patent
      foramen ovale as well as atrial septal defect closures has remained stable, while
      the number of transcatheter aortic valve implantations and transcatheter mitral
      valve repairs has shown a fourfold increase.

PMID- 28504237
TI  - Turkey: coronary and structural heart interventions from 2010 to 2015.
AB  - Growing populations and ageing demographics lead to an increased burden of
      ischaemic heart disease and related cardiovascular interventions, resulting in
      pressure on healthcare systems. Although the healthcare system in Turkey has
      undergone comprehensive remodelling over the last decade, there are many
      challenges to overcome, including better reimbursement for cardiovascular
      interventions, standardisation of interventional cardiology services and research
      related activities. In this manuscript, we present an overview of coronary and
      structural heart interventions in Turkey, as well as providing information on
      current reimbursement policies and the healthcare system.

PMID- 28504238
TI  - United Kingdom: coronary and structural heart interventions from 2010 to 2015.
AB  - In the United Kingdom, a clinical data set is completed for every patient
      undergoing coronary intervention and certain structural interventions, and sent
      to central servers in the National Institute for Cardiovascular Outcomes Research
      (NICOR) on behalf of the British Cardiovascular Intervention Society (BCIS).
      These data are linked to the national mortality register. In addition, data are
      obtained about the structure of healthcare provision using an annual survey.
      Analyses of these data are provided for different audiences in several formats.
      Public reports of individual consultant operator activity and risk-adjusted
      outcomes from percutaneous coronary intervention (PCI) have also been produced
      annually since 2012. Transcatheter aortic valve implantation (TAVI) has been
      performed since 2007. Over 2,000 cases were performed in 2015, giving a rate of
      30 per million population. Complications to discharge have fallen as case mix has
      changed and technologies improved. While the mean age has remained about 81
      years, the logistic EuroSCORE of patients treated by TAVI has fallen from about
      22 in 2010 to 18 in 2015. Tracked 30-day mortality was 3.7% in 2014. Left atrial
      appendage occlusion and patent foramen ovale (PFO) closure for stroke, and the
      use of the MitraClip(r) system (Abbott Vascular, Santa Clara, CA, USA) for mitral
      regurgitation have been funded through a process called "commissioning through
      evaluation".

PMID- 28504240
TI  - MALDI-TOF MS in the Microbiology Laboratory: Current Trends.
AB  - Within less than a decade matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) has become a gold standard for microbial
      identification in clinical microbiology laboratories. Besides identification of
      microorganisms the typing of single strains as well as the antibiotic and
      antimycotic resistance testing has come into focus in order to speed up the
      microbiological diagnostic. However, the full potential of MALDI-TOF MS has not
      been tapped yet and future technological advancements will certainly expedite
      this method towards novel applications and enhancement of current practice. So,
      the following chapter shall be rather a brainstorming and forecast of how MALDI
      TOF MS will develop to influence clinical diagnostics and microbial research in
      the future. It shall open up the stage for further discussions and does not claim
      for overall validity.

PMID- 28504239
TI  - Sustained safety and clinical performance of a drug-eluting absorbable metal
      scaffold up to 24 months: pooled outcomes of BIOSOLVE-II and BIOSOLVE-III.
AB  - AIMS: We aimed to assess the safety and performance of the DREAMS 2G scaffold up
      to 24 months post implant. METHODS AND RESULTS: The present study population
      comprises a total of 184 patients with 189 lesions who were enrolled in the
      prospective, multicentre BIOSOLVE-II and BIOSOLVE-III trials. Clinical follow-up
      was scheduled at one, six, 12, 24 and 36 months. The present report includes
      pooled follow-up data at six months and BIOSOLVE-II data at 24 months. Patients
      were 65.5+/-10.8 years old, and lesions were 12.5+/-5.1 mm long with reference
      diameters of 2.7+/-0.4 mm. Procedural success was obtained in 97.8%. At six
      months, the composite clinical endpoint target lesion failure was 3.3% (95% CI:
      1.2-7.1), based on two cardiac deaths (1.1%, one unknown and one not device
      related), one target vessel myocardial infarction (0.6%), and three clinically
      driven target lesion revascularisations (1.7%). For BIOSOLVE-II at 24 months, the
      target lesion failure rate was 5.9% (95% CI: 2.4-11.8), based on two cardiac
      deaths (1.7%), one target vessel myocardial infarction (0.9%) and four target
      lesion revascularisations (3.4%). There was no definite or probable scaffold
      thrombosis. CONCLUSIONS: The present analysis provides additional evidence on the
      safety of a drug-eluting absorbable metal scaffold with promising clinical
      outcomes up to 24 months and absence of definite or probable scaffold thrombosis.

PMID- 28504241
TI  - Antiviral drug resistance and hepatitis B: a continuing public health problem.
AB  - The use of selective antiviral therapy has been very successful in controlling
      HBV replication in individuals, leading to a reduction in disease progression and
      mortality. However, the use of first-generation therapies, often the only
      available option in low-resource settings, can result in a high prevalence of
      drug resistance mutations. Variants selected by antiviral therapies targeting the
      viral polymerase can also result in variants in the viral envelope. These
      variants can allow the virus to escape the host immune response. The effect of
      antiviral selection pressure on viral variants that may contribute to immune
      escape requires further investigation.

PMID- 28504242
TI  - Simultaneous microfluidic spinning of multiple strands of submicron fiber for the
      production of free-standing porous membranes for biological application.
AB  - Microfibers produced using electrospinning and microfluidics-based technologies
      have been developed as a powerful tool in tissue engineering applications such as
      drug delivery and scaffolds. The applications of these fibers, however, have been
      limited because of the hazardous solvents used to make them, difficulties in
      controlling the pore sizes of their membrane forms, and downscaling the size of
      the fiber. Nevertheless, extending the use of these fibers, for example in the
      production of a free-standing porous membrane appropriate for cell-based
      research, is highly needed for tissue engineering, organ-on-a-chip, and drug
      delivery research and applications. Here, we fabricated a free-standing porous
      membrane by using a novel method that involved simultaneously spinning multiple
      strands of submicron-thick 'noodle-like' fibers. In addition to the novelty of
      the single noodle fiber in overcoming the size-reducing limitations of
      conventional microfluidic spinning methods, these fibers can hence form the units
      of 'noodle membranes' whose pores have sizes that the convention electrospinning
      method cannot achieve. We confirmed the potential of the noodle membrane to serve
      as a free-standing porous membrane in two simple experiments. Also, we found that
      noodle membranes have an advantage in loading different amounts of different
      materials in itself that it was also shown to be of use as a new type of scaffold
      for complex tissue regeneration. Therefore, the proposed noodle membrane can be
      an effective tool in tissue engineering applications and biological studies.

PMID- 28504243
TI  - Cancers of the appendix. Case report and literatures review.
AB  - : Cancers of appendix are very uncommon. As reported in the case of 85 years old
      man, that underwent right emicolectomy with restoration of bowel continuity, the
      appendix was found to be gangrenous and perforated during the surgery. The
      hystology that comes out was adenocarcinoma of appendix that after 1 yars of
      follow up ramanins asymptomatic. At last the emicolectomy rappresent the best
      surgical treatment for all appendix neoplasm, that could be recognised from the
      surgeon when possible wiht intraoperavite histological examination. KEY WORDS:
      Appendix, Cancer, Incidental diagnosis, Right emicolectomy.

PMID- 28504244
TI  - Mid-infrared coincidence measurements on twin photons at room temperature.
AB  - Quantum measurements using single-photon detectors are opening interesting new
      perspectives in diverse fields such as remote sensing, quantum cryptography and
      quantum computing. A particularly demanding class of applications relies on the
      simultaneous detection of correlated single photons. In the visible and near
      infrared wavelength ranges suitable single-photon detectors do exist. However,
      low detector quantum efficiency or excessive noise has hampered their mid
      infrared (MIR) counterpart. Fast and highly efficient single-photon detectors are
      thus highly sought after for MIR applications. Here we pave the way to quantum
      measurements in the MIR by the demonstration of a room temperature coincidence
      measurement with non-degenerate twin photons at about 3.1 MUm. The experiment is
      based on the spectral translation of MIR radiation into the visible region, by
      means of efficient up-converter modules. The up-converted pairs are then detected
      with low-noise silicon avalanche photodiodes without the need for cryogenic
      cooling.

PMID- 28504246
TI  - Diffusive and martensitic nucleation kinetics in solid-solid transitions of
      colloidal crystals.
AB  - Solid-solid transitions between crystals follow diffusive nucleation, or various
      diffusionless transitions, but these kinetics are difficult to predict and
      observe. Here we observed the rich kinetics of transitions from square lattices
      to triangular lattices in tunable colloidal thin films with single-particle
      dynamics by video microscopy. Applying a small pressure gradient in defect-free
      regions or near dislocations markedly transform the diffusive nucleation with an
      intermediate-stage liquid into a martensitic generation and oscillation of
      dislocation pairs followed by a diffusive nucleus growth. This transformation is
      neither purely diffusive nor purely martensitic as conventionally assumed but a
      combination thereof, and thus presents new challenges to both theory and the
      empirical criterion of martensitic transformations. We studied how pressure,
      density, grain boundary, triple junction and interface coherency affect the
      nucleus growth, shape and kinetic pathways. These novel microscopic kinetics cast
      new light on control solid-solid transitions and microstructural evolutions in
      polycrystals.

PMID- 28504245
TI  - Macrophage-derived IL-1alpha promotes sterile inflammation in a mouse model of
      acetaminophen hepatotoxicity.
AB  - The metabolic intermediate of acetaminophen (APAP) can cause severe hepatocyte
      necrosis, which triggers aberrant immune activation of liver non-parenchymal
      cells (NPC). Overzealous hepatic inflammation determines the morbidity and
      mortality of APAP-induced liver injury (AILI). Interleukin-1 receptor (IL-1R)
      signaling has been shown to play a critical role in various inflammatory
      conditions, but its precise role and underlying mechanism in AILI remain
      debatable. Herein, we show that NLRP3 inflammasome activation of IL-1beta is
      dispensable to AILI, whereas IL-1alpha, the other ligand of IL-1R1, accounts for
      hepatic injury by a lethal dose of APAP. Furthermore, Kupffer cells function as a
      major source of activated IL-1alpha in the liver, which is activated by damaged
      hepatocytes through TLR4/MyD88 signaling. Finally, IL-1alpha is able to
      chemoattract and activate CD11b+Gr-1+ myeloid cells, mostly neutrophils and
      inflammatory monocytes, to amplify deteriorated inflammation in the lesion.
      Therefore, this work identifies that MyD88-dependent activation of IL-1alpha in
      Kupffer cells plays a central role in the immunopathogenesis of AILI and
      implicates that IL-1alpha is a promising therapeutic target for AILI treatment.

PMID- 28504248
TI  - The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer
      cells via abrogating the function of the AHA1/Hsp90 complex.
AB  - The flavonoid quercetin exhibits significant anticancer activities with few side
      effects. In the current study, we characterized TL-2-8, a quercetin derivative,
      as a novel anticancer agent in vitro and in vivo. Cell proliferation and
      viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay,
      respectively. Cell death was examined using PI staining or a TUNEL assay.
      Mitophagy was determined by measuring autophagic flux and by confocal imaging.
      Protein expression was examined by Western blotting. We found that TL-2-8
      selectively inhibited the proliferation and decreased the viability of various
      cancer cells (the anti-proliferation IC50 values in MDA-MB-231, MDA-MB-468 and
      MCF-7 breast cancer cells at 72 h were 8.28, 8.56, and 9.58 MUmol/L,
      respectively), and it displayed only slight cytotoxicity against normal MCF-10A
      and HEK-293 cells. In MDA-MB-231 and MDA-MB-468 breast cancer cells, TL-2-8
      treatment induced the degradation of multiple Hsp90 client proteins without
      inducing Hsp70. TL-2-8 (3, 6, 12 MUmol/L) dose-dependently inhibited the
      expression of AHA1, an activator of Hsp90 ATPase, and decreased Hsp90-AHA1
      complex formation, leading to decreased Hsp90 chaperone function and reduced polo
      like kinase 1 (PLK1) signaling. Consequently, impaired mitophagy was induced via
      the downregulation of lysosomal-associated membrane protein 2 (LAMP2). The in
      vivo anticancer effects of TL-2-8 were evaluated in an MDA-MB-231 breast cancer
      xenograft model, which was treated with TL-2-8 (25, 50, 100 mg.kg-1.d-1, po).
      Administration of TL-2-8 resulted in tumor growth inhibition rates of 37.9%,
      58.9% and 70.9%, respectively, whereas quercetin treatment (100 mg.kg-1.d-1, po)
      produced only a lower tumor growth inhibition rate (49.5%). Furthermore, TL-2-8
      treatment significantly extended the lifespan of mice bearing MDA-MB-231 breast
      cancer cell xenografts. Our results demonstrate that TL-2-8 induces significant
      cell death and immature mitophagy in breast cancer cells in vitro and in vivo via
      AHA1 abrogation.

PMID- 28504247
TI  - Actomyosin meshwork mechanosensing enables tissue shape to orient cell force.
AB  - Sculpting organism shape requires that cells produce forces with proper
      directionality. Thus, it is critical to understand how cells orient the
      cytoskeleton to produce forces that deform tissues. During Drosophila
      gastrulation, actomyosin contraction in ventral cells generates a long, narrow
      epithelial furrow, termed the ventral furrow, in which actomyosin fibres and
      tension are directed along the length of the furrow. Using a combination of
      genetic and mechanical perturbations that alter tissue shape, we demonstrate that
      geometrical and mechanical constraints act as cues to orient the cytoskeleton and
      tension during ventral furrow formation. We developed an in silico model of two
      dimensional actomyosin meshwork contraction, demonstrating that actomyosin
      meshworks exhibit an inherent force orienting mechanism in response to mechanical
      constraints. Together, our in vivo and in silico data provide a framework for
      understanding how cells orient force generation, establishing a role for
      geometrical and mechanical patterning of force production in tissues.

PMID- 28504249
TI  - Treating breast cancer metastasis with cabazitaxel-loaded polymeric micelles.
AB  - Cancer metastasis is the primary cause of high mortality in breast cancer
      patients. In this study, we loaded an anti-cancer drug, cabazitaxel (CTX), into
      polymeric micelles (CTX-loaded polymeric micelles, PCMs), and explored their
      therapeutic efficacy in breast cancer metastasis. The characteristics of PCMs
      were investigated, and their anti-metastatic efficacy was assessed using in vitro
      and in vivo evaluations. PCMs had an average diameter of 50.13+/-11.96 nm with a
      CTX encapsulation efficiency of 97.02%+/-0.97%. PCMs could be effectively
      internalized into metastatic 4T1 breast cancer cells in vitro. CTX (10 ng/mL) or
      an equivalent concentration in PCMs did not significantly affected the viability
      of 4T1 cells, but dramatically decreased the cell migration activities. In an
      orthotopic metastatic breast cancer model, intravenously administered PCMs could
      be efficiently delivered to the tumor sites, resulting in a 71.6% inhibition of
      tumor growth and a 93.5% reduction of lung metastases. Taken together, our
      results verify the anti-metastatic efficacy of PCMs, thus providing an
      encouraging strategy for treating breast cancer metastasis.

PMID- 28504250
TI  - Curcumin enhances vascular contractility via induction of myocardin in mouse
      smooth muscle cells.
AB  - A variety of cardiovascular diseases is accompanied by the loss of vascular
      contractility. This study sought to investigate the effects of curcumin, a
      natural polyphenolic compound present in turmeric, on mouse vascular
      contractility and the underlying mechanisms. After mice were administered
      curcumin (100 mg.kg-1.d-1, ig) for 6 weeks, the contractile responses of the
      thoracic aorta to KCl and phenylephrine were significantly enhanced compared with
      the control group. Furthermore, the contractility of vascular smooth muscle (SM)
      was significantly enhanced after incubation in curcumin (25 MUmol/L) for 4 days,
      which was accompanied by upregulated expression of SM marker contractile proteins
      SM22alpha and SM alpha-actin. In cultured vascular smooth muscle cells (VSMCs),
      curcumin (10, 25, 50 MUmol/L) significantly increased the expression of
      myocardin, a "master regulator" of SM gene expression. Curcumin treatment also
      significantly increased the levels of caveolin-1 in VSMCs. We found that as a
      result of the upregulation of caveolin-1, curcumin blocked the activation of
      notch1 and thereby abolished Notch1-inhibited myocardin expression. Knockdown of
      caveolin-1 or activation of Notch1 signaling with Jagged1 (2 MUg/mL) diminished
      these effects of curcumin in VSMCs. These findings suggest that curcumin induces
      the expression of myocardin in mouse smooth muscle cells via a variety of
      mechanisms, including caveolin-1-mediated inhibition of notch1 activation and
      Notch1-mediated repression of myocardin expression. This may represent a novel
      pathway, through which curcumin protects blood vessels via the beneficial
      regulation of SM contractility.

PMID- 28504251
TI  - Programmable co-delivery of the immune checkpoint inhibitor NLG919 and
      chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric
      prodrug carrier.
AB  - To achieve synergistic therapeutic efficacy and prevent cancer relapse,
      chemotherapy and immunotherapy have been combined as a new modality for tumor
      treatment. In this work, we designed a redox-responsive immunostimulatory
      polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune
      checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG
      containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles
      that served as a carrier to load DOX (DOX/PSSN10 micelles). DOX/PSSN10 micelles
      displayed spherical morphology with a size of ~170 nm. DOX was effectively loaded
      into PSSN10 micelles with a loading efficiency of 84.0%. In vitro DOX release
      studies showed that rapid drug release could be achieved in the highly redox
      environment after intracellular uptake by tumor cells. In 4T1.2 tumor-bearing
      mice, DOX/PSSN10 micelles exhibited greater accumulation of DOX and NLG in the
      tumor tissues compared with other organs. The PSSN10 carrier dose-dependently
      enhanced T-cell immune responses in the lymphocyte-Panc02 co-culture experiments,
      and significantly inhibited tumor growth in vivo. DOX/PSSN10 micelles showed
      potent cytotoxicity in vitro against 4T1.2 mouse breast cancer cells and PC-3
      human prostate cancer cells comparable to that of DOX. In 4T1.2 tumor-bearing
      mice, DOX/PSSN10 mixed micelles (5 mg DOX/kg, iv) was more effective than DOXIL
      (a clinical formulation of liposomal DOX) or free DOX in inhibiting the tumor
      growth and prolonging the survival of the treated mice. In addition, a more
      immunoactive tumor microenvironment was observed in the mice treated with PSSN10
      or DOX/PSSN10 micelles compared with the other treatment groups. In conclusion,
      systemic delivery of DOX via PSSN10 nanocarrier results in synergistic anti-tumor
      activity.

PMID- 28504253
TI  - Dynamic diversity of synthetic supramolecular polymers in water as revealed by
      hydrogen/deuterium exchange.
AB  - Numerous self-assembling molecules have been synthesized aiming at mimicking both
      the structural and dynamic properties found in living systems. Here we show the
      application of hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to
      unravel the nanoscale organization and the structural dynamics of synthetic
      supramolecular polymers in water. We select benzene-1,3,5-tricarboxamide (BTA)
      derivatives that self-assemble in H2O to illustrate the strength of this
      technique for supramolecular polymers. The BTA structure has six exchangeable
      hydrogen atoms and we follow their exchange as a function of time after diluting
      the H2O solution with a 100-fold excess of D2O. The kinetic H/D exchange profiles
      reveal that these supramolecular polymers in water are dynamically diverse; a
      notion that has previously not been observed using other techniques. In addition,
      we report that small changes in the molecular structure can be used to control
      the dynamics of synthetic supramolecular polymers in water.

PMID- 28504255
TI  - Energy efficiency to reduce residential electricity and natural gas use under
      climate change.
AB  - Climate change could significantly affect consumer demand for energy in
      buildings, as changing temperatures may alter heating and cooling loads. Warming
      climates could also lead to the increased adoption and use of cooling
      technologies in buildings. We assess residential electricity and natural gas
      demand in Los Angeles, California under multiple climate change projections and
      investigate the potential for energy efficiency to offset increased demand. We
      calibrate residential energy use against metered data, accounting for differences
      in building materials and appliances. Under temperature increases, we find that
      without policy intervention, residential electricity demand could increase by as
      much as 41-87% between 2020 and 2060. However, aggressive policies aimed at
      upgrading heating/cooling systems and appliances could result in electricity use
      increases as low as 28%, potentially avoiding the installation of new generation
      capacity. We therefore recommend aggressive energy efficiency, in combination
      with low-carbon generation sources, to offset projected increases in residential
      energy demand.

PMID- 28504254
TI  - Neural circuits for long-term water-reward memory processing in thirsty
      Drosophila.
AB  - The intake of water is important for the survival of all animals and drinking
      water can be used as a reward in thirsty animals. Here we found that thirsty
      Drosophila melanogaster can associate drinking water with an odour to form a
      protein-synthesis-dependent water-reward long-term memory (LTM). Furthermore, we
      found that the reinforcement of LTM requires water-responsive dopaminergic
      neurons projecting to the restricted region of mushroom body (MB) beta' lobe,
      which are different from the neurons required for the reinforcement of learning
      and short-term memory (STM). Synaptic output from alpha'beta' neurons is required
      for consolidation, whereas the output from gamma and alphabeta neurons is
      required for the retrieval of LTM. Finally, two types of MB efferent neurons
      retrieve LTM from gamma and alphabeta neurons by releasing glutamate and
      acetylcholine, respectively. Our results therefore cast light on the cellular and
      molecular mechanisms responsible for processing water-reward LTM in Drosophila.

PMID- 28504256
TI  - Explosive eruption, flank collapse and megatsunami at Tenerife ca. 170 ka.
AB  - Giant mass failures of oceanic shield volcanoes that generate tsunamis
      potentially represent a high-magnitude but low-frequency hazard, and it is
      actually difficult to infer the mechanisms and dynamics controlling them. Here we
      document tsunami deposits at high elevation (up to 132 m) on the north-western
      slopes of Tenerife, Canary Islands, as a new evidence of megatsunami generated by
      volcano flank failure. Analyses of the tsunami deposits demonstrate that two main
      tsunamis impacted the coasts of Tenerife 170 kyr ago. The first tsunami was
      generated during the submarine stage of a retrogressive failure of the northern
      flank of the island, whereas the second one followed the debris avalanche of the
      subaerial edifice and incorporated pumices from an on-going ignimbrite-forming
      eruption. Coupling between a massive retrogressive flank failure and a large
      explosive eruption represents a new type of volcano-tectonic event on oceanic
      shield volcanoes and a new hazard scenario.

PMID- 28504258
TI  - Neuroimmunology: Macrophages help you burn energy.

PMID- 28504252
TI  - Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung
      cancers: challenges and opportunities.
AB  - Lung cancer is the second most prevalent and the deadliest among all cancer
      types. Chemotherapy is recommended for lung cancers to control tumor growth and
      to prolong patient survival. Systemic chemotherapy typically has very limited
      efficacy as well as severe systemic adverse effects, which are often attributed
      to the distribution of anticancer drugs to non-targeted sites. In contrast,
      inhalation routes permit the delivery of drugs directly to the lungs providing
      high local concentrations that may enhance the anti-tumor effect while
      alleviating systemic adverse effects. Preliminary studies in animals and humans
      have suggested that most inhaled chemotherapies are tolerable with manageable
      pulmonary adverse effects, including cough and bronchospasm. Promoting the
      deposition of anticancer drugs in tumorous cells and minimizing access to healthy
      lung cells can further augment the efficacy and reduce the risk of local
      toxicities caused by inhaled chemotherapy. Sustained release and tumor
      localization characteristics make nanoparticle formulations a promising candidate
      for the inhaled delivery of chemotherapeutic agents against lung cancers.
      However, the physiology of respiratory tracts and lung clearance mechanisms
      present key barriers for the effective deposition and retention of inhaled
      nanoparticle formulations in the lungs. Recent research has focused on the
      development of novel formulations to maximize lung deposition and to minimize
      pulmonary clearance of inhaled nanoparticles. This article systematically reviews
      the challenges and opportunities for the pulmonary delivery of nanoparticle
      formulations for the treatment of lung cancers.

PMID- 28504257
TI  - Early life factors that affect allergy development.
AB  - The incidence of allergic disease continues to rise in industrialized countries.
      The rapid increase in the incidence of allergic disease throughout the past half
      century suggests that recently altered environmental factors are driving allergy
      development. Accumulating evidence suggests that environmental experiences that
      occur during the first months of life can influence the risk of allergic
      sensitization. In this Review, we present the evidence relating to specific early
      life exposures that affect future allergy development, and discuss how these
      exposures may promote either tolerance or allergic sensitization.

PMID- 28504259
TI  - Controllable cyanation of carbon-hydrogen bonds by zeolite crystals over
      manganese oxide catalyst.
AB  - The synthesis of organic nitriles without using toxic cyanides is in great demand
      but challenging to make. Here we report an environmentally benign and cost
      efficient synthesis of nitriles from the direct oxidative cyanation of primary
      carbon-hydrogen bonds with easily available molecular oxygen and urea. The key to
      this success is to design and synthesize manganese oxide catalysts fixed inside
      zeolite crystals, forming a manganese oxide catalyst with zeolite sheath (MnOx@S
      1), which exhibits high selectivity for producing nitriles by efficiently
      facilitating the oxidative cyanation reaction and hindering the side hydration
      reaction. The work delineates a sustainable strategy for synthesizing nitriles
      while avoiding conventional toxic cyanide, which might open a new avenue for
      selective transformation of carbon-hydrogen bonds.

PMID- 28504261
TI  - Progressive approach to eruption at Campi Flegrei caldera in southern Italy.
AB  - Unrest at large calderas rarely ends in eruption, encouraging vulnerable
      communities to perceive emergency warnings of volcanic activity as false alarms.
      A classic example is the Campi Flegrei caldera in southern Italy, where three
      episodes of major uplift since 1950 have raised its central district by about 3 m
      without an eruption. Individual episodes have conventionally been treated as
      independent events, so that only data from an ongoing episode are considered
      pertinent to evaluating eruptive potential. An implicit assumption is that the
      crust relaxes accumulated stress after each episode. Here we apply a new model of
      elastic-brittle failure to test the alternative view that successive episodes
      promote a long-term accumulation of stress in the crust. The results provide the
      first quantitative evidence that Campi Flegrei is evolving towards conditions
      more favourable to eruption and identify field tests for predictions on how the
      caldera will behave during future unrest.

PMID- 28504260
TI  - New Blatter-type radicals from a bench-stable carbene.
AB  - Stable benzotriazinyl radicals (Blatter's radicals) recently attracted
      considerable interest as building blocks for functional materials. The existing
      strategies to derivatize Blatter's radicals are limited, however, and synthetic
      routes are complex. Here, we report that an inexpensive, commercially available,
      analytical reagent Nitron undergoes a previously unrecognized transformation in
      wet acetonitrile in the presence of air to yield a new Blatter-type radical with
      an amide group replacing a phenyl at the C(3)-position. This one-pot reaction of
      Nitron provides access to a range of previously inaccessible triazinyl radicals
      with excellent benchtop stabilities. Mechanistic investigation suggests that the
      reaction starts with a hydrolytic cleavage of the triazole ring followed by
      oxidative cyclization. Several derivatives of Nitron were prepared and converted
      into Blatter-type radicals to test the synthetic value of the new reaction. These
      results significantly expand the scope of using functionalized benzotriazinyls as
      stable radical building blocks.

PMID- 28504262
TI  - Density structure of Earth's lowermost mantle from Stoneley mode splitting
      observations.
AB  - Advances in our understanding of Earth's thermal evolution and the style of
      mantle convection rely on robust seismological constraints on lateral variations
      of density. The large-low-shear-wave velocity provinces (LLSVPs) atop the core
      mantle boundary beneath Africa and the Pacific are the largest structures in the
      lower mantle, and hence severely affect the convective flow. Here, we show that
      anomalous splitting of Stoneley modes, a unique class of free oscillations that
      are perturbed primarily by velocity and density variations at the core-mantle
      boundary, is explained best when the overall density of the LLSVPs is lower than
      the surrounding mantle. The resolved density variations can be explained by the
      presence of post-perovskite, chemical heterogeneity or a combination of the two.
      Although we cannot rule out the presence of a ~100-km-thick denser-than-average
      basal structure, our results support the hypothesis that LLSVPs signify large
      scale mantle upwelling in two antipodal regions of the mantle.

PMID- 28504263
TI  - Dehydration-driven stress transfer triggers intermediate-depth earthquakes.
AB  - Intermediate-depth earthquakes (30-300 km) have been extensively documented
      within subducting oceanic slabs, but their mechanics remains enigmatic. Here we
      decipher the mechanism of these earthquakes by performing deformation experiments
      on dehydrating serpentinized peridotites (synthetic antigorite-olivine
      aggregates, minerals representative of subduction zones lithologies) at upper
      mantle conditions. At a pressure of 1.1 gigapascals, dehydration of deforming
      samples containing only 5 vol% of antigorite suffices to trigger acoustic
      emissions, a laboratory-scale analogue of earthquakes. At 3.5 gigapascals,
      acoustic emissions are recorded from samples with up to 50 vol% of antigorite.
      Experimentally produced faults, observed post-mortem, are sealed by fluid-bearing
      micro-pseudotachylytes. Microstructural observations demonstrate that antigorite
      dehydration triggered dynamic shear failure of the olivine load-bearing network.
      These laboratory analogues of intermediate-depth earthquakes demonstrate that
      little dehydration is required to trigger embrittlement. We propose an
      alternative model to dehydration-embrittlement in which dehydration-driven stress
      transfer, rather than fluid overpressure, causes embrittlement.

PMID- 28504264
TI  - Absorptive pinhole collimators for ballistic Dirac fermions in graphene.
AB  - Ballistic electrons in solids can have mean free paths far larger than the
      smallest features patterned by lithography. This has allowed development and
      study of solid-state electron-optical devices such as beam splitters and quantum
      point contacts, which have informed our understanding of electron flow and
      interactions. Recently, high-mobility graphene has emerged as an ideal two
      dimensional semimetal that hosts unique chiral electron-optical effects due to
      its honeycomb crystalline lattice. However, this chiral transport prevents the
      simple use of electrostatic gates to define electron-optical devices in graphene.
      Here we present a method of creating highly collimated electron beams in graphene
      based on collinear pairs of slits, with absorptive sidewalls between the slits.
      By this method, we achieve beams with angular width 18 degrees  or narrower, and
      transmission matching classical ballistic predictions.

PMID- 28504267
TI  - An in-plane magnetic chiral dichroism approach for measurement of intrinsic
      magnetic signals using transmitted electrons.
AB  - Electron energy-loss magnetic chiral dichroism is a powerful technique that
      allows the local magnetic properties of materials to be measured quantitatively
      with close-to-atomic spatial resolution and element specificity in the
      transmission electron microscope. Until now, the technique has been restricted to
      measurements of the magnetic circular dichroism signal in the electron beam
      direction. However, the intrinsic magnetization directions of thin samples are
      often oriented in the specimen plane, especially when they are examined in
      magnetic-field-free conditions in the transmission electron microscope. Here, we
      introduce an approach that allows in-plane magnetic signals to be measured using
      electron magnetic chiral dichroism by selecting a specific diffraction geometry.
      We compare experimental results recorded from a cobalt nanoplate with simulations
      to demonstrate that an electron magnetic chiral dichroism signal originating from
      in-plane magnetization can be detected successfully.

PMID- 28504265
TI  - In vitro evolution of an influenza broadly neutralizing antibody is modulated by
      hemagglutinin receptor specificity.
AB  - The relatively recent discovery and characterization of human broadly
      neutralizing antibodies (bnAbs) against influenza virus provide valuable insights
      into antiviral and vaccine development. However, the factors that influence the
      evolution of high-affinity bnAbs remain elusive. We therefore explore the
      functional sequence space of bnAb C05, which targets the receptor-binding site
      (RBS) of influenza haemagglutinin (HA) via a long CDR H3. We combine saturation
      mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to
      H1 and H3 HAs. The C05 variants evolve up to 20-fold higher affinity but increase
      specificity to each HA subtype used in the selection. Structural analysis reveals
      that the fine specificity is strongly influenced by a highly conserved
      substitution that regulates receptor binding in different subtypes. Overall, this
      study suggests that subtle natural variations in the HA RBS between subtypes and
      species may differentially influence the evolution of high-affinity bnAbs.

PMID- 28504268
TI  - Observation of the universal magnetoelectric effect in a 3D topological
      insulator.
AB  - The electrodynamics of topological insulators (TIs) is described by modified
      Maxwell's equations, which contain additional terms that couple an electric field
      to a magnetization and a magnetic field to a polarization of the medium, such
      that the coupling coefficient is quantized in odd multiples of alpha/4pi per
      surface. Here we report on the observation of this so-called topological
      magnetoelectric effect. We use monochromatic terahertz (THz) spectroscopy of TI
      structures equipped with a semitransparent gate to selectively address surface
      states. In high external magnetic fields, we observe a universal Faraday rotation
      angle equal to the fine structure constant alpha=e2/2hc (in SI units) when a
      linearly polarized THz radiation of a certain frequency passes through the two
      surfaces of a strained HgTe 3D TI. These experiments give insight into axion
      electrodynamics of TIs and may potentially be used for a metrological definition
      of the three basic physical constants.

PMID- 28504266
TI  - Low phosphate activates STOP1-ALMT1 to rapidly inhibit root cell elongation.
AB  - Environmental cues profoundly modulate cell proliferation and cell elongation to
      inform and direct plant growth and development. External phosphate (Pi)
      limitation inhibits primary root growth in many plant species. However, the
      underlying Pi sensory mechanisms are unknown. Here we genetically uncouple two Pi
      sensing pathways in the root apex of Arabidopsis thaliana. First, the rapid
      inhibition of cell elongation in the transition zone is controlled by
      transcription factor STOP1, by its direct target, ALMT1, encoding a malate
      channel, and by ferroxidase LPR1, which together mediate Fe and peroxidase
      dependent cell wall stiffening. Second, during the subsequent slow inhibition of
      cell proliferation in the apical meristem, which is mediated by LPR1-dependent,
      but largely STOP1-ALMT1-independent, Fe and callose accumulate in the stem cell
      niche, leading to meristem reduction. Our work uncovers STOP1 and ALMT1 as a
      signalling pathway of low Pi availability and exuded malate as an unexpected
      apoplastic inhibitor of root cell wall expansion.

PMID- 28504270
TI  - Antiplatelet therapy: New score for predicting bleeding risk after DAPT.

PMID- 28504269
TI  - YAP regulates cell mechanics by controlling focal adhesion assembly.
AB  - Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing
      modifications in extracellular matrix (ECM) composition and mechanics. The
      regulation of their activity has been described by a hierarchical model in which
      elements of Hippo pathway are under the control of focal adhesions (FAs). Here we
      unveil the molecular mechanism by which cell spreading and RhoA GTPase activity
      control FA formation through YAP to stabilize the anchorage of the actin
      cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional
      function and involves the activation of genes encoding for integrins and FA
      docking proteins. Tuning YAP transcriptional activity leads to the modification
      of cell mechanics, force development and adhesion strength, and determines cell
      shape, migration and differentiation. These results provide new insights into the
      mechanism of YAP mechanosensing activity and qualify this Hippo effector as the
      key determinant of cell mechanics in response to ECM cues.

PMID- 28504271
TI  - Probing nanofriction and Aubry-type signatures in a finite self-organized system.
AB  - Friction in ordered atomistic layers plays a central role in various nanoscale
      systems ranging from nanomachines to biological systems. It governs transport
      properties, wear and dissipation. Defects and incommensurate lattice constants
      markedly change these properties. Recently, experimental systems have become
      accessible to probe the dynamics of nanofriction. Here, we present a model system
      consisting of laser-cooled ions in which nanofriction and transport processes in
      self-organized systems with back action can be studied with atomic resolution. We
      show that in a system with local defects resulting in incommensurate layers,
      there is a transition from sticking to sliding with Aubry-type signatures. We
      demonstrate spectroscopic measurements of the soft vibrational mode driving this
      transition and a measurement of the order parameter. We show numerically that
      both exhibit critical scaling near the transition point. Our studies demonstrate
      a simple, well-controlled system in which friction in self-organized structures
      can be studied from classical- to quantum-regimes.

PMID- 28504274
TI  - Link between light-triggered Mg-banding and chamber formation in the planktic
      foraminifera Neogloboquadrina dutertrei.
AB  - The relationship between seawater temperature and the average Mg/Ca ratios in
      planktic foraminifera is well established, providing an essential tool for
      reconstructing past ocean temperatures. However, many species display alternating
      high and low Mg-bands within their shell walls that cannot be explained by
      temperature alone. Recent experiments demonstrate that intrashell Mg variability
      in Orbulina universa, which forms a spherical terminal shell, is paced by the
      diurnal light/dark cycle. Whether Mg-heterogeneity is also diurnally paced in
      species with more complex shell morphologies is unknown. Here we show that high
      Mg/Ca-calcite forms at night in cultured specimens of the multi-chambered species
      Neogloboquadrina dutertrei. Our results demonstrate that N. dutertrei adds a
      significant amount of calcite, and nearly all Mg-bands, after the final chamber
      forms. These results have implications for interpreting patterns of calcification
      in N. dutertrei and suggest that diurnal Mg-banding is an intrinsic component of
      biomineralization in planktic foraminifera.

PMID- 28504273
TI  - Legionella effector Lpg1137 shuts down ER-mitochondria communication through
      cleavage of syntaxin 17.
AB  - During infection of macrophages, the pathogenic bacterium Legionella pneumophila
      secretes effector proteins that induce the conversion of the plasma membrane
      derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole.
      These ER-like vacuoles are ultimately fused with the ER, where the pathogen
      replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine
      protease that targets the mitochondria and their associated membranes. Lpg1137
      binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) protein that is known to participate in the
      regulation of mitochondrial dynamics through interaction with the mitochondrial
      fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L
      and other SNAREs in starved cells. Cleavage of syntaxin 17 inhibits not only
      autophagy but also staurosporine-induced apoptosis occurring in a Bax, Drp1
      dependent manner. Thus, L. pneumophila can shut down ER-mitochondria
      communication through cleavage of syntaxin 17.

PMID- 28504272
TI  - Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other
      proteins.
AB  - Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological
      functions, including stress resistance, adipogenesis, cell senescence and energy
      production. Sirt1 can be activated by energy deprivation, but the mechanism is
      poorly understood. Here, we report that Sirt1 is negatively regulated by ATP,
      which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1
      activity by impairing the CTD's ability to bind to the deacetylase domain as well
      as its ability to function as the substrate recruitment site. ATP, but not NAD+,
      causes a conformational shift to a less compact structure. Mutations that prevent
      ATP binding increase Sirt1's ability to promote stress resistance and inhibit
      adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to
      other proteins, thereby converting them into energy-regulated proteins. These
      discoveries provide insight into how extreme energy deprivation can impact Sirt1
      activity and underscore the complex nature of Sirt1 structure and regulation.

PMID- 28504275
TI  - Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between
      frog life history phases.
AB  - Anuran amphibians undergo major morphological transitions during development, but
      the contribution of their markedly different life-history phases to
      macroevolution has rarely been analysed. Here we generate testable predictions
      for coupling versus uncoupling of phenotypic evolution of tadpole and adult life
      history phases, and for the underlying expression of genes related to
      morphological feature formation. We test these predictions by combining evidence
      from gene expression in two distantly related frogs, Xenopus laevis and
      Mantidactylus betsileanus, with patterns of morphological evolution in the entire
      radiation of Madagascan mantellid frogs. Genes linked to morphological structure
      formation are expressed in a highly phase-specific pattern, suggesting uncoupling
      of phenotypic evolution across life-history phases. This gene expression pattern
      agrees with uncoupled rates of trait evolution among life-history phases in the
      mantellids, which we show to have undergone an adaptive radiation. Our results
      validate a prevalence of uncoupling in the evolution of tadpole and adult
      phenotypes of frogs.

PMID- 28504277
TI  - Role of dietary onion in modifying the faecal bile acid content in rats fed a
      high-cholesterol diet.
AB  - The determination of faecal bile patterns offers new opportunities in the search
      for non-invasive biomarkers of disease status. The objective of this study was to
      describe the shifts in faecal bile acid (BA) composition induced by feeding a
      high-cholesterol/cholic acid diet (HC) over 7 weeks of experimental feeding in
      Wistar rats, and to evaluate the effect of onion included as a functional
      ingredient (HCO). A HPLC-MS/MS method allowed the detection of 29 bile acids, 10
      of which were tentatively identified and 12 confirmed and quantified by means of
      standards and calibration curves. The excretion of bile acids revealed a
      discriminating bile acid profile between the HC and HCO groups compared with the
      C group. HCO feeding indicated significant changes in specific primary and
      secondary BA in both the unconjugated and conjugated forms caused by the addition
      of the onion ingredient to the diet. The results suggest that the induction of
      microbiome modifications by the HC and HCO diets acts as a critical modifier of
      the faecal bile acid composition. These modifications might reflect and be linked
      to changes in the reabsorption of BA at an intestinal level and the process of BA
      deconjugation in the course of hypercholesterolemia.

PMID- 28504278
TI  - High-frequency linear rheology of hydrogels probed by ultrasound-driven
      microbubble dynamics.
AB  - Ultrasound-driven microbubble dynamics are central to biomedical applications,
      from diagnostic imaging to drug delivery and therapy. In therapeutic
      applications, the bubbles are typically embedded in tissue, and their dynamics
      are strongly affected by the viscoelastic properties of the soft solid medium.
      While the behaviour of bubbles in Newtonian fluids is well characterised, a
      fundamental understanding of the effect on ultrasound-driven bubble dynamics of a
      soft viscoelastic medium is still being developed. We characterised the resonant
      behaviour in ultrasound of isolated microbubbles embedded in agarose gels,
      commonly used as tissue-mimicking phantoms. Gels with different viscoelastic
      properties were obtained by tuning agarose concentration, and were characterised
      by standard rheological tests. Isolated bubbles (100-200 MUm) were excited by
      ultrasound (10-50 kHz) at small pressure amplitudes (<1 kPa), to ensure that the
      deformation of the material and the bubble dynamics remained in the linear
      regime. The radial dynamics of the bubbles were recorded by high-speed video
      microscopy. Resonance curves were measured experimentally and fitted to a model
      combining the Rayleigh-Plesset equation governing bubble dynamics, with the
      Kelvin-Voigt model for the viscoelastic medium. The resonance frequency of the
      bubbles was found to increase with increasing shear modulus of the medium, with
      implications for optimisation of imaging and therapeutic ultrasound protocols. In
      addition, the viscoelastic properties inferred from ultrasound-driven bubble
      dynamics differ significantly from those measured at low frequency with the
      rheometer. Hence, rheological characterisation of biomaterials for medical
      ultrasound applications requires particular attention to the strain rate applied.

PMID- 28504276
TI  - Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour
      microenvironment.
AB  - Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs)
      is one of the most effective immunotherapies against haematological malignancies,
      but significant clinical success has not yet been achieved in solid tumours due
      in part to the strong immunosuppressive tumour microenvironment. Here, we show
      that suppression of CTL killing by CD4+CD25+Foxp3+ regulatory T cell (Treg) is in
      part mediated by TGFbeta-induced inhibition of inositol trisphosphate (IP3)
      production, leading to a decrease in T cell receptor (TCR)-dependent
      intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling
      in adoptively transferred CTLs enhances T cell activation and IFN-gamma
      production in vitro, leading to a significant reduction in tumour growth in mice.
      Altogether, our findings indicate that the targeted optogenetic stimulation of
      intracellular Ca2+ signal allows for the remote control of cytotoxic effector
      functions of adoptively transferred T cells with outstanding spatial resolution
      by boosting T cell immune responses at the tumour sites.

PMID- 28504279
TI  - The structural impact of water sorption on device-quality melanin thin films.
AB  - The melanins are a class of pigmentary bio-macromolecules ubiquitous in the
      biosphere. They possess an intriguing set of physico-chemical properties and have
      been shown to exhibit hybrid protonic-electronic electrical conductivity, a
      feature derived from a process termed chemical self-doping driven by the sorption
      of water. Although the mechanism underlying the electrical conduction has been
      established, how the sorbed water interacts with the melanin structure at the
      physical level has not. Herein we use neutron reflectometry to study changes in
      the structure of synthetic melanin thin films as a function of H2O and D2O vapour
      pressure. Water is found to be taken up evenly throughout the films, and by
      employing the contrast effect, the existence of labile protons through reversible
      deuterium exchange is demonstrated. Finally, we determine a sorption isotherm to
      enable quantification of the melanin-water interactions.

PMID- 28504284
TI  - Fabrication and characterization of self-folding thermoplastic sheets using
      unbalanced thermal shrinkage.
AB  - Self-folding or micro-origami technologies are actively investigated as a novel
      manufacturing process to fabricate three-dimensional macro/micro-structures. In
      this paper, we present a simple process to produce a self-folding structure with
      a biaxially oriented polystyrene sheet (BOPS) or Shrinky Dinks. A BOPS sheet is
      known to shrink to one-third of its original size in plane, when it is heated
      above 160  degrees C. A grid pattern is engraved on one side of the BOPS film
      with a laser engraver to decrease the thermal shrinkage of the engraved side. The
      thermal shrinkage of the non-engraved side remains the same and this unbalanced
      thermal shrinkage causes folding of the structure as the structure shrinks at
      high temperature. We investigated the self-folding mechanism and characterized
      how the grid geometry, the grid size, and the power of the laser engraver affect
      the bending curvature. The developed fabrication process to locally modulate
      thermomechanical properties of the material by engraving the grid pattern and the
      demonstrated design methodology to harness the unbalanced thermal shrinkage can
      be applied to develop complicated self-folding macro/micro structures.

PMID- 28504285
TI  - A van der Waals DFT study of chain length dependence of alkanethiol adsorption on
      Au(111): physisorption vs. chemisorption.
AB  - The energetics and structures of physisorbed and chemisorbed alkanethiols on
      Au(111) have been systematically investigated up to 10 carbon atoms using van der
      Waals (vdW) corrected density functional theory (DFT) calculations. The role of
      chain length, tilting angle and coverage on the adsorption characteristics has
      been examined to elucidate the energetics and plausible transformation mechanisms
      between lying down and standing up phases. Coverage and size dependent chain
      chain electronic interactions counteract with the alkyl chain-gold surface
      interactions and the surface relaxation of the metal in the formation of standing
      up monolayer structures. For the striped phases of long chain alkanethiols,
      however, our calculations on decanethiol indicate alkyl chain-gold surface
      interactions to be strong enough to force the molecule to be perfectly parallel
      to the surface by lifting a gold atom up, in agreement with the proposed models
      for this film in the literature.

PMID- 28504280
TI  - Metabolic profile and underlying improved bio-activity of Fructus aurantii
      immaturus by human intestinal bacteria.
AB  - Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L.
      or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the
      metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile
      to evaluate the antioxidant and anti-inflammatory activities of FAI and the
      transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was
      anaerobically incubated with human intestinal bacterial suspensions for 48 h at
      37  degrees C. Liquid chromatography-hybridised with quadrupole-time-of-flight
      mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total
      of 45 compounds were identified in FAI, eleven of which were metabolized by human
      intestinal bacteria. Nine major metabolites were identified as eriodictyol,
      naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin
      and diosmetin. The metabolic profile of FAI was elucidated on the basis of
      metabolite information. We found that the concentrations of acetic, propionic and
      butyric acids in FAI culture were all increased during fermentation relative to
      those of the control. Further bioactive evaluations showed that TFAI exhibited
      more potent antioxidant and anti-inflammatory abilities than FAI in vitro.
      Additionally, in vivo experiment confirmed that FAI significantly attenuated the
      blood endotoxin and TNF-alpha levels in the conventional rats compared to those
      of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a
      key role in the antioxidant and anti-inflammatory capacities of FAI.

PMID- 28504286
TI  - Ag-Catalyzed difluorohydration of beta-alkynyl ketones for diastereoselective
      synthesis of 1,5-dicarbonyl compounds.
AB  - A new catalytic difluorohydration of beta-alkynyl ketones using NFSI as the
      fluorinating reagent has been established, diastereoselectively furnishing a
      range of structurally diverse difluoride 1,5-dicarbonyl products through C(sp3)-H
      fluorination. Notably, the sterically encumbered t-butyl functionality located at
      the alpha-position of the carbonyl group of substrates 1 showed excellent
      diastereoselectivity (up to >99 : 1 dr). The reaction enabled multiple bond
      forming events including two C(sp3)-F formation through Ag-catalysis to provide a
      highly efficient and practical method toward difluoride 1,5-dicarbonyls, some of
      which were successfully converted into difluorinated isoquinolines.

PMID- 28504287
TI  - gamma-Oryzanol nanoemulsions produced by a low-energy emulsification method: an
      evaluation of process parameters and physicochemical stability.
AB  - gamma-Oryzanol is a natural antioxidant and nutraceutical compound, which makes
      it a good candidate for nutraceuticals, food supplements and pharmaceutical
      preparations. However, the incorporation of gamma-oryzanol into aqueous
      formulations is rather difficult and its bioavailability can be severely
      decreased because of its water-insoluble property. In this study, gamma-oryzanol
      enriched nanoemulsion based fish oil and medium-chain triglyceride as carrier
      oils were proposed. The main objective was to optimize process parameters to form
      stable nanoemulsions and evaluate their physicochemical stability. The
      formulations of stable gamma-oryzanol nanoemulsions were composed of 10% mixed
      carrier oils (weight ratio of fish oil to medium-chain triglyceride = 3 : 7) and
      10% mixed surfactants (weight ratio of Tween 80 to Span 20 = 3 : 1). The
      nanoemulsions were stable at a broad pH range of 2-7 and high salt concentrations
      (<=0.8 mol L-1) and sucrose levels (<=16%). The nanoemulsions were much more
      stable at heating temperatures below 50  degrees C than at elevated heating
      temperatures (60 and 70  degrees C). The nanoemulsions maintained their physical
      stability at various storage temperatures (5-37  degrees C) for 18 days.
      Nanoemulsions at 5 and 23  degrees C had lower peroxide values and anisidine
      values than those at an elevated storage temperature (37  degrees C). These
      results demonstrate that the low-energy emulsification method can produce gamma
      oryzanol-enriched nanoemulsions using fish oil and medium-chain triglyceride as
      carrier oils, and provide useful information for producing bioactive lipids
      loaded nanoemulsions for food systems, personal care and pharmaceutical products.

PMID- 28504288
TI  - Understanding nanoparticle porosity via nanoimpacts and XPS: electro-oxidation of
      platinum nanoparticle aggregates.
AB  - The porosity of platinum nanoparticle aggregates (PtNPs) is investigated
      electrochemically via particle-electrode impacts and by XPS. The mean charge per
      oxidative transient is measured from nanoimpacts; XPS shows the formation of PtO
      and PtO2 in relative amounts defined by the electrode potential and an average
      oxidation state is deduced as a function of potential. The number of platinum
      atoms oxidised per PtNP is calculated and compared with two models: solid and
      porous spheres, within which there are two cases: full and surface oxidation.
      This allows insight into extent to which the internal surface of the aggregate is
      'seen' by the solution and is electrochemically active.

PMID- 28504289
TI  - An ionic coordination hybrid hydrogel for bioseparation.
AB  - An ionic coordination hybrid hydrogel is formed with ionic and covalent
      crosslinked networks via one-step copolymation. It is demonstrated that the
      hybrid crosslinker gel is used as a separation matrix for bioseparation, showing
      high separation efficiency, in contrast to traditional polyacrylamide gels. The
      hydrogel might serve as a novel matrix for bioseparation.

PMID- 28504290
TI  - Effect of body deformability on microswimming.
AB  - In this work we consider the following question: given a mechanical microswimming
      mechanism, does increased deformability of the swimmer body hinder or promote the
      motility of the swimmer? To answer this we run immersed-boundary-lattice
      Boltzmann simulations of a microswimmer composed of deformable beads connected
      with springs. We find that the same deformations in the beads can result in
      different effects on the swimming velocity, namely an enhancement or a reduction,
      depending on the other parameters. To understand this we determine analytically
      the velocity of the swimmer, starting from the forces driving the motion and
      assuming that the deformations in the beads are known as functions of time and
      are much smaller than the beads themselves. We find that to the lowest order,
      only the driving frequency mode of the surface deformations contributes to the
      swimming velocity, and comparison to the simulations shows that both the velocity
      promoting and velocity-hindering effects of bead deformability are reproduced
      correctly by the theory in the limit of small bead deformations. For the case of
      active deformations we show that there are critical values of the spring constant
      - which for a general swimmer corresponds to its main elastic degree of freedom -
      which decide whether the body deformability is beneficial for motion or not.

PMID- 28504291
TI  - Strain-induced stiffening of nanocellulose-reinforced poly(vinyl alcohol)
      hydrogels mimicking collagenous soft tissues.
AB  - Soft tissues possess remarkable mechanical strength for their high water content,
      which is hard to mimic in synthetic materials. Here, we demonstrate how strain
      induced stiffening in hydrogels plays a major role in mimicking the mechanical
      properties of collagenous soft tissues. In particular, nanocellulose reinforced
      polyvinyl alcohol (PVA) hydrogels of exceptionally high water content (90-93 wt%)
      are shown to exhibit collagen-like mechanical behavior typical for soft tissues.
      High water content and co-existence of both soft and rigid domains in the gel
      network are the main factors responsible for strain-induced stiffening. This
      observed effect due to the alignment of rigid components of the hydrogel is
      simulated through modeling and visualized through strain-induced birefringence
      experiments. Design parameters such as nanocellulose aspect ratio and solvent
      composition are also shown to be important to control the mechanical properties.
      In addition, owing to their transparency (90-95% at 550 nm) and hyperelastic
      properties (250-350% strain), the described hydrogels are promising materials for
      biomedical applications, especially in ophthalmology.

PMID- 28504292
TI  - Microstructure degradation of Ni/CGO anodes for solid oxide fuel cells after long
      operation time using 3D reconstructions by FIB tomography.
AB  - Solid oxide fuel cells (SOFCs) are electrochemical conversion devices, which
      essentially consist of two porous electrodes separated by a dense, oxide ion
      conducting electrolyte. The performance and the durability of SOFCs strongly
      depend on the electrode microstructure. In this paper, the impact of a relatively
      long exposure time (up to 20 000 h) under realistic operation terms (temperature
      (T) = 850  degrees C, current density (J) = 190-250 mA cm-2) in the kinetics of
      microstructural degradation are investigated for porous nickel (Ni)/ceria
      gadolinium oxide (CGO) anodes, to understand the microstructural evolution in
      SOFC cermet anodes. A combined system of Focused Ion Beam (FIB) and Scanning
      Electron Microscope (SEM) tomography was used to analyze various anode
      microstructures aged during different operating times (2500 h, 15 000 h and 20
      000 h). The methodologies of image acquisition as well as the segmentation and
      the object recognition were improved, offering a reliable quantification of Ni
      grain growth, connectivity, tortuosity factor and triple phase boundary length
      (TPBL). The representative volume element (RVE) was also studied, and its
      dependence on aging time was confirmed. To construct a volume that can be
      accurate and representative for the whole sample, the necessary corresponding 3D
      reconstruction size was adjusted by increasing operating time, in order to
      suppress the influence of microstructure variation caused by Ni and CGO
      agglomeration. Statistically significant 3D microstructural changes were observed
      in the anode by increasing the operating time, including nickel particle size
      distribution, changes in connectivity of the ceramic part (CGO) and a significant
      decrease of contiguous triple phase boundary densities. Additional qualitative
      observations were done in order to gain a complete insight of the degradation
      phenomena in nickel based cermet anodes.

PMID- 28504293
TI  - Quantifying the sensitivity of the network structure and properties from
      simultaneous measurements during photopolymerization.
AB  - We present a method that combines experimental and computational approaches to
      assess a comprehensive set of structural and functional evolution during a
      network formation process via photopolymerization. Our work uses the simultaneous
      measurement of the degree of conversion, polymerization stress, the change in
      reaction temperature, and shrinkage strain in situ. These measurements are
      combined with the theory of viscoelastic materials to deduce the relaxation time
      and frequency-dependent modulus of the polymerizing network. The relaxation time
      and degree of conversion are used to demonstrate the effect of processing
      parameters (e.g. curing protocol adjusted by the light intensity) in creating
      different network structures for the same initial resin. We describe experimental
      trends using effective medium calculations on a cross-linked polymer network
      model. In particular, we show that the effect of curing conditions on the spatial
      heterogeneity in crosslink density can be quantified using multiparametric
      measurements and modeling. Collectively, the present method is a way to examine
      holistically the complex structural and functional evolution of the network
      formation process.

PMID- 28504295
TI  - Increased permeability of oxygen atoms through graphene with ripples.
AB  - Graphene is an ideal membrane for selective separation because of its unique
      properties and single-layer structure. Considerable efforts have been made to
      alter the permeability of graphene. In this study, we investigate the pathways
      for an oxygen atom to pass through graphene sheets. We also identify the effect
      of the ripple's curvature in graphene sheets on the energy barrier of permeation
      through density functional theory calculations. Results show that oxygen atoms
      can easily pass through the concave side of graphene ripples with a large
      curvature. The analysis of transition states reveals that the space where an
      oxygen atom passes through keeps an almost identical structure with similar bond
      lengths regardless of the curvature. We find that the Cu(111) substrate may draw
      out the C-C bond lengths of graphene at the Cu(111) surface because of the strong
      interaction between the graphene edge and copper atoms. Consequently, the energy
      barrier of the permeation of oxygen atoms through graphene is reduced. These
      results suggest that the rippling of graphene significantly affects its
      permeation.

PMID- 28504294
TI  - Ultrasensitive fluorescence detection of transcription factors based on
      kisscomplex formation and the T7 RNA polymerase amplification method.
AB  - Herein, we report a kisscomplex based protein fluorescence assay (KPFA) method,
      which employed the formation of a kisscomplex and the T7 RNA polymerase
      amplification method, for the assay of transcription factors with high
      sensitivity.

PMID- 28504296
TI  - Supplementation with n-3, n-6, n-9 fatty acids in an insulin-resistance animal
      model: does it improve VLDL quality?
AB  - : Insulin-resistance (IR), of increased cardiovascular risk, is characterized by
      the production of altered VLDL with greater atherogenicity. Dietary fatty acids
      influence the type of circulating VLDL. But, it is not clear how dietary fatty
      acids impact VLDL characteristics in IR. AIM: to evaluate the effects of n-3, n-6
      and n-9 fatty acid supplementation on preventing atherogenic alterations in VLDL,
      in a diet-induced IR rat model. Male Wistar rats (180-200 g) were fed: standard
      diet (control, n = 8) and a sucrose rich diet (30% sucrose in water/12 weeks,
      SRD; n = 24). Simultaneously, SRD was subdivided into SRD-C (standard diet), and
      three other groups supplemented (15% w/w) with: fish oil (SRD-n3), sunflower oil
      (SRD-n6) and high oleic sunflower oil (SRD-n9). Lipid profile, free fatty acids,
      glucose, and insulin were measured. Isolated VLDL (d < 1.006 g ml-1) was
      characterized by chemical composition and size (size exclusion-HPLC). In
      comparison with SRD-C: SRD-n3 showed an improved lipoprotein profile (p < 0.01),
      with lower levels of insulin and HOMA-IR (p < 0.05). SRD-n6 showed increased
      levels of HDL-cholesterol and lower insulin levels. SRD-n9 did not exhibit
      differences in lipid and IR profile, and even favored weight gain and visceral
      fat. Only SRD-n3 prevented the alterations in VLDL-TG% (54.2 +/- 4.4% vs. 68.6 +/
      8.2, p < 0.05) and showed lower large VLDL-% (22.5[19.7-35.6] vs. 49.1[15.5
      82.0], p < 0.05), while SRD-n6 and SRD-n9 did not show effects. CONCLUSION: In
      IR, while n-3 PUFA showed expected favorable effects, supplementation with n-6
      PUFA and n-9 MUFA did not prevent atherogenic alterations of VLDL. Thus, the
      recommendations of supplementation with these fatty acids in general diet should
      be revised.

PMID- 28504297
TI  - Elemental bioimaging by means of LA-ICP-OES: investigation of the calcium, sodium
      and potassium distribution in tobacco plant stems and leaf petioles.
AB  - Laser ablation-inductively coupled plasma-optical emission spectroscopy (LA-ICP
      OES) is presented as a valuable tool for elemental bioimaging of alkali and earth
      alkali elements in plants. Whereas LA-ICP-OES is commonly used for micro analysis
      of solid samples, laser ablation-inductively coupled plasma-mass spectrometry (LA
      ICP-MS) has advanced to the gold standard for bioimaging. However, especially for
      easily excitable and ubiquitous elements such as alkali and earth alkali
      elements, LA-ICP-OES holds some advantages regarding simultaneous detection,
      costs, contamination, and user-friendliness. This is demonstrated by determining
      the calcium, sodium and potassium distribution in tobacco plant stem and leaf
      petiole tissues. A quantification of the calcium contents in a concentration
      range up to 1000 MUg g-1 using matrix-matched standards is presented as well. The
      method is directly compared to a LA-ICP-MS approach by analyzing parallel slices
      of the same samples.

PMID- 28504298
TI  - Bio-inspired hierarchical micro- and nano-wrinkles obtained via mechanically
      directed self-assembly on shape-memory polymers.
AB  - Inspired by complex multi-functional leaf and petal surfaces, we introduce a
      mechanically directed self-assembly process to create linearly oriented micro-
      and nanosized surface wrinkles in an all-polymer bi-layer system based on a shape
      memory polymer substrate. By systematically investigating the influence of
      coating thickness and substrate programming strain on wrinkle period and height,
      we reveal how to control the structure size from a few hundred nanometers up to
      several microns. As a parameter unique to shape memory polymers, we demonstrate
      that the temperature during the recovery process can also be utilized to tailor
      the structure dimensions. Furthermore, we advance the method with a second
      structuring step to mimic the hierarchically structured petal surfaces of tulips
      and daisies. The presented structuring method provides a large-scale, mold-free,
      and very cost-effective way for the full-polymer fabrication of micro and sub
      microstructures with adjustable structure size and intrinsic irregularity.

PMID- 28504300
TI  - Effect of protection against hot climate on growth performance, physiological
      response and endocrine profile of growing lambs under semi-arid tropical
      environment.
AB  - In the hot semi-arid tropical region, extreme summer is a major constraint in
      sheep production. The growth performance of growing lambs is impaired during the
      summer. Therefore, the present study was conducted to assess the effect of
      protection against hot climate on growth performance, physiological response, and
      endocrine profile of growing lambs under semi-arid tropical environment. All the
      data in the experiment were presented as mean +/- SE. Thirty Malpura lambs with
      the age of 122.7 +/- 6.05 days and body weight of 19.52 +/- 0.42 kg were allotted
      into three groups, viz. G1 (control, lambs kept in open area under tree shade),
      G2 (lambs kept in conventional asbestos-roofed shed), and G3 (lambs kept in
      designed shed). The allotment was based on their initial body weight so that the
      mean body weight of each group was similar. In all three types of protection,
      lambs were provided with sufficient space to move and social interaction. In
      asbestos-roofed shed (G2), all the four sides from ground to the roof were fenced
      with strong galvanized iron chain link. But in G3, all the four sides were
      constructed in a manner that there was 0.13 m air space between inner and outer
      solid brick columns of the wall up to 1.37 m height, and rest up to the roof was
      fenced with bamboo splint net. The air space between the two columns of the wall
      was filled with sand, and it was kept in moist condition by continuous water
      drips which provide extra evaporative cooling. The designed shed was basically
      constructed with bamboo. Tree shade was assured under the natural shades of large
      trees. The shaded area was protected by wire fences. The experiment was conducted
      for 45 days during very high temperature (May-June). The lambs were provided with
      ad libitum green fodder, dry roughage, 300 g concentrate, and ad libitum drinking
      water. The respiration rate at morning and afternoon, pulse rate at morning and
      afternoon and rectal temperature at afternoon was significantly (P < 0.05) lower
      in lambs of G3 as compared to other groups. The final body weight did not differ
      significantly between the groups, but average daily gain (g/day) was higher in G3
      (150.06 +/- 11.13) as compared to the G1 (109.69 +/- 18.10). The feed conversion
      rate (FCR) was significantly (P < 0.05) better in G3 (5.49 +/- 0.08) as compared
      to G1 (7.65 +/- 0.08) and G2 (6.60 +/- 0.08). The hemoglobin level was
      significantly (P < 0.05) higher in G1. The endocrine profile did not vary
      significantly (P > 0.05) among the groups, but insulin-like growth factor-1 (IGF
      1) was higher in G3. It can be concluded from this study the lambs provided with
      better protection during summer remained in more comfortable condition, showed
      better FCR, and although not statistically significant showed better growth
      performance.

PMID- 28504302
TI  - Guidance to the International Medical Guide for Ships 3<sup>rd</sup> edition.

PMID- 28504299
TI  - What We Know About Stage II and III Colon Cancer: It's Still Not Enough.
AB  - The introduction of oxaliplatin as adjuvant treatment for stage III colon cancer
      in 2004 has been the last practice changing progress in adjuvant treatment for
      patients with early colon cancer. Since then, many prognostic and predictive
      biomarkers have been studied, but only DNA mismatch repair status has been
      validated as having an important prognostic value. Accordingly, TNM and clinical
      pathological patterns, such as pT4 lesions and lymph node sampling <12 nodes, are
      the main factors that guide physicians' choice regarding adjuvant treatment. More
      recently, many biomarkers showed promising results: POLE, ErbB2, CDX2, SMAD4,
      BRAF and KRAS. In addition to these, immune-contexture, molecular classification,
      and gene signatures could become new ways to better classify colon cancer
      patients with more discriminatory power than TNM. The aim of this review is to
      report the state-of-the-art of prognostic and predictive factors in the adjuvant
      setting and which of these could modify clinical practice and maybe replace TNM
      classification.

PMID- 28504301
TI  - First report on serological evidence of bovine viral diarrhea virus (BVDV)
      infection in farmed and free ranging mithuns (Bos frontalis).
AB  - Despite reports of BVDV infection in several domestic and wild ruminants, no
      information exists for mithun (Bos frontalis) species. Hence, this study was
      undertaken to determine prevalence of BVDV infection in mithuns, which contribute
      significantly to local economy in the North Eastern region of India. Blood and
      serum samples were collected between 2013 and 2016 from mithuns (n = 466)
      belonging to the states of Nagaland, Mizoram, and Arunachal Pradesh. Serum
      samples were tested for BVDV antibodies by a commercial ELISA and leukocytes were
      tested for BVDV by real-time RT-PCR. The overall true seroprevalence rate was
      13.1% (95% confidence interval, CI: 6.9-17.8%) with higher prevalence in mithuns
      reared under semi-intensive system (27.5%) than in free-ranging mithuns (7.6%).
      Among the three states, seroprevalence (16.2%) was highest in Nagaland, while
      prevalence rates varied markedly among geographical locations. Age-wise data
      showed highest seroprevalence rate in >6-year-old animals (20.6%) than 2-6 years
      old (16.9%), 6 months-2 years old (8.5%), and <6-month-old animals (11.3%). The
      seroprevalence was higher in males (20.9%) than in females (12.1%). Among the
      four mithun strains, higher prevalence was evident in Manipur (30.3%) than
      Arunachal (21.3%), Nagaland (11.7%), and Mizoram strain (10.2%). However, no BVDV
      genomic RNA could be detected. The results provide first serological evidence of
      BVDV infection in mithun species and extend the knowledge on BVDV host range. The
      baseline data will help further investigations on epidemiology of BVD in mithun
      and its impact on mithun production.

PMID- 28504303
TI  - Distracted Walking, Bicycling, and Driving: Systematic Review and Meta-Analysis
      of Mobile Technology and Youth Crash Risk.
AB  - This article examined the impact of mobile technology on young pedestrians,
      bicyclists, and drivers. A systematic search yielded 41 articles meeting
      inclusion criteria: peer-reviewed, published before February 1, 2016, behavioral
      outcome related to pedestrian, bicycling, or driving in the presence of mobile
      technology use, youth sample. Eleven studies were meta-analyzed to evaluate
      increased risk for crash/near-crash while distracted. Risk of bias and quality of
      research were assessed. Across methodologies, developmental stages, and type of
      distracting task, mobile technology use impairs youth safety on the road. Quality
      of evidence was low (pedestrian) to moderate (driving). Findings are discussed
      from the perspective of cognitive and visual distractions. Policy and behavioral
      efforts should continue to reduce mobile technology use in transportation
      settings.

PMID- 28504304
TI  - Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR
      B1.
AB  - Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors
      characterized by their capacity to remove extraneous or modified self
      macromolecules from circulation, thus avoiding the accumulation of noxious agents
      in the extracellular space. This scavenging activity makes SRs important
      molecules for host defense and homeostasis. In turn, SRs keep the activation of
      the steady-state immune response in check, and participate as co-receptors in the
      priming of the effector immune responses when the macromolecules are associated
      with a threat that might compromise host homeostasis. Therefore, SRs built up
      sophisticated sensor mechanisms controlling the immune system, which may be
      exploited to develop novel drugs for cancer immunotherapy. In this review, we
      focus on the regulation of the anti-tumor immune response by two paradigmatic
      SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger
      receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of
      SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of
      SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate
      both the complexity of targeting SRs in cancer immunotherapy and also the
      opportunities offered by such an approach.

PMID- 28504306
TI  - Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme
      EhDbr1 reveals a catalytic Zn2+ /Mn2+ heterobinucleation.
AB  - The RNA lariat debranching enzyme, Dbr1, is a metallophosphoesterase that cleaves
      2'-5' phosphodiester bonds within intronic lariats. Previous reports have
      indicated that Dbr1 enzymatic activity is supported by diverse metal ions
      including Ni2+ , Mn2+ , Mg2+ , Fe2+ , and Zn2+ . While in initial structures of
      the Entamoeba histolytica Dbr1 only one of the two catalytic metal-binding sites
      were observed to be occupied (with a Mn2+ ion), recent structures determined a
      Zn2+ /Fe2+ heterobinucleation. We solved a high-resolution X-ray crystal
      structure (1.8 A) of the E. histolytica Dbr1 and determined a Zn2+ /Mn2+
      occupancy. ICP-AES corroborate this finding, and in vitro debranching assays with
      fluorescently labeled branched substrates confirm activity.

PMID- 28504305
TI  - Intranuclear and higher-order chromatin organization of the major histone gene
      cluster in breast cancer.
AB  - Alterations in nuclear morphology are common in cancer progression. However, the
      degree to which gross morphological abnormalities translate into compromised
      higher-order chromatin organization is poorly understood. To explore the
      functional links between gene expression and chromatin structure in breast
      cancer, we performed RNA-seq gene expression analysis on the basal breast cancer
      progression model based on human MCF10A cells. Positional gene enrichment
      identified the major histone gene cluster at chromosome 6p22 as one of the most
      significantly upregulated (and not amplified) clusters of genes from the normal
      like MCF10A to premalignant MCF10AT1 and metastatic MCF10CA1a cells. This cluster
      is subdivided into three sub-clusters of histone genes that are organized into
      hierarchical topologically associating domains (TADs). Interestingly, the sub
      clusters of histone genes are located at TAD boundaries and interact more
      frequently with each other than the regions in-between them, suggesting that the
      histone sub-clusters form an active chromatin hub. The anchor sites of loops
      within this hub are occupied by CTCF, a known chromatin organizer. These histone
      genes are transcribed and processed at a specific sub-nuclear microenvironment
      termed the major histone locus body (HLB). While the overall chromatin structure
      of the major HLB is maintained across breast cancer progression, we detected
      alterations in its structure that may relate to gene expression. Importantly,
      breast tumor specimens also exhibit a coordinate pattern of upregulation across
      the major histone gene cluster. Our results provide a novel insight into the
      connection between the higher-order chromatin organization of the major HLB and
      its regulation during breast cancer progression.

PMID- 28504307
TI  - Family-based promotion of mental health in children affected by HIV: a pilot
      randomized controlled trial.
AB  - BACKGROUND: Children affected by HIV are at risk for poor mental health. We
      conducted a pilot randomized controlled trial (RCT) of the Family Strengthening
      Intervention (FSI-HIV), a family home-visiting intervention to promote mental
      health and improve parent-child relationships in families with caregivers living
      with HIV, hypothesizing that child and family outcomes would be superior to usual
      care social work services. METHODS: Eighty two families (N = 170 children, 48.24%
      female; N = 123 caregivers, 68.29% female) with at least one HIV-positive
      caregiver (n = 103, 83.74%) and school-aged child (ages 7-17) (HIV+ n = 21,
      12.35%) were randomized to receive FSI-HIV or treatment-as-usual (TAU). Local
      research assistants blind to treatment conducted assessments of child mental
      health, parenting practices, and family functioning at baseline, post
      intervention, and 3-month follow-up. Multilevel modeling assessed effects of FSI
      HIV on outcomes across three time points. TRIAL REGISTRATION: NCT01509573, 'Pilot
      Feasibility Trial of the Family Strengthening Intervention in Rwanda (FSI-HIV
      R).'
      https://clinicaltrials.gov/ct2/show/;NCT01509573?term=Pilot+Feasibility+Trial+of+
      he+Family+Strengthening+Intervention+in+Rwanda+%28FSI-HIV-R%29&rank=1. RESULTS:
      At 3-month follow-up, children in FSI-HIV showed fewer symptoms of depression
      compared to TAU by both self-report (beta = -.246; p = .009) and parent report
      (beta = -.174; p = .035) but there were no significant differences by group on
      conduct problems, functional impairment, family connectedness, or parenting.
      CONCLUSIONS: Family-based prevention has promise for reducing depression symptoms
      in children affected by HIV. Future trials should examine the effects of FSI-HIV
      over time in trials powered to examine treatment mediators.

PMID- 28504309
TI  - Deletion of the short N-terminal extension in OCP reveals the main site for FRP
      binding.
AB  - The orange carotenoid protein (OCP) plays a key role in cyanobacterial
      photoprotection. Photoconversion entails structural rearrangements in OCP that
      are required for its binding to phycobilisome, thereby inducing excitation energy
      dissipation. Detachment of OCP from phycobilisome requires the fluorescence
      recovery protein (FRP). It is considered that OCP interacts with FRP only in the
      photoactivated state; however, the binding site for FRP is currently unknown. As
      an important stabilizing element in orange OCP, the short alphaA-helix within the
      N-terminal extension (NTE) binds to the C-terminal domain (CTD), but unfolds upon
      photoactivation and interferes with phycobilisome binding. Here, we demonstrate
      that the NTE shares specific structural and functional similarities with FRP and
      discover the main site of OCP-FRP interactions in the OCP-CTD.

PMID- 28504308
TI  - Brainstem as a developmental gateway to social attention.
AB  - BACKGROUND: Evolution preserves social attention due to its key role in
      supporting survival. Humans are attracted to social cues from infancy, but the
      neurobiological mechanisms for the development of social attention are unknown.
      An evolutionary-based, vertical-hierarchical theoretical model of self-regulation
      suggests that neonatal brainstem inputs are key for the development of well
      regulated social attention. METHODS: Neonates born preterm (N = 44, GA 34 w.)
      were recruited and diagnosed at birth as a function of their auditory brainstem
      evoked responses (ABR). Participants enrolled in a prospective 8-year-long,
      double-blind, follow-up study comparing participants with brainstem dysfunctions
      and well-matched controls. Groups had comparable fetal, neonatal, and familial
      characteristics. Methods incorporated EEG power analysis and gaze tracking during
      the Attention Network Test (ANT, four cue types, and two targets) and a Triadic
      Gaze Engagement task (TGE, three social cue levels). RESULTS: Results showed that
      neonatal brainstem compromise is related to long-term changes in Alpha- and Theta
      band power asymmetries (p < .034, p < .016, respectively), suggesting suppressed
      bottom-up input needed to alert social attention. Gaze tracking indicated
      dysregulated arousal-modulated attention (p < .004) and difficulty in gaze
      engagement to socially neutral compared to nonsocial cues (p < .012).
      CONCLUSIONS: Integrating models of Autism and cross-species data with current
      long-term follow-up of infants with discrete neonatal brainstem dysfunction
      suggests neonatal brainstem input as a gateway for bottom-up regulation of social
      attention.

PMID- 28504311
TI  - Ultrasound-Guided Injection of the Temporalis Tendon: A Novel Technique.
AB  - A novel technique, ultrasound-guided injection of the temporalis tendon in
      adults, is described. Ultrasound-guided injection of the temporalis tendon is
      based on visualization of the temporalis muscle, temporalis tendon, and coronoid
      process. A practical step-by-step guide to doing the procedure is given. This
      technique is effective and reproducible. Two patients successfully treated with
      this technique will be briefly discussed. The anatomic location and size of the
      temporalis tendon make it mandatory to use ultrasound to ensure precision.

PMID- 28504310
TI  - Aerobic capacity mediates susceptibility for the transition from steatosis to
      steatohepatitis.
AB  - KEY POINTS: Low intrinsic aerobic capacity is associated with increased all-cause
      and liver-related mortality in humans. Low intrinsic aerobic capacity in the low
      capacity runner (LCR) rat increases susceptibility to acute and chronic high
      fat/high-sucrose diet-induced steatosis, without observed increases in liver
      inflammation. Addition of excess cholesterol to a high-fat/high-sucrose diet
      produced greater steatosis in LCR and high capacity runner (HCR) rats. However,
      the LCR rat demonstrated greater susceptibility to increased liver inflammatory
      and apoptotic markers compared to the HCR rat. The progressive non-alcoholic
      fatty liver disease observed in the LCR rats following western diet feeding was
      associated with further declines in liver fatty acid oxidation and mitochondrial
      respiratory capacity compared to HCR rats. ABSTRACT: Low aerobic capacity
      increases risk for non-alcoholic fatty liver disease and liver-related disease
      mortality, but mechanisms mediating these effects remain unknown. We recently
      reported that rats bred for low aerobic capacity (low capacity runner; LCR)
      displayed susceptibility to high fat diet-induced steatosis in association with
      reduced hepatic mitochondrial fatty acid oxidation (FAO) and respiratory capacity
      compared to high aerobic capacity (high capacity runner; HCR) rats. Here we
      tested the impact of aerobic capacity on susceptibility for progressive liver
      disease following a 16-week 'western diet' (WD) high in fat (45% kcal),
      cholesterol (1% w/w) and sucrose (15% kcal). Unlike previously with a diet high
      in fat and sucrose alone, the inclusion of cholesterol in the WD induced
      hepatomegaly and steatosis in both HCR and LCR rats, while producing greater
      cholesterol ester accumulation in LCR compared to HCR rats. Importantly, WD-fed
      low-fitness LCR rats displayed greater inflammatory cell infiltration, serum
      alanine transaminase, expression of hepatic inflammatory markers (F4/80, MCP-1,
      TLR4, TLR2 and IL-1beta) and effector caspase (caspase 3 and 7) activation
      compared to HCR rats. Further, LCR rats had greater WD-induced decreases in
      complete FAO and mitochondrial respiratory capacity. Intrinsic aerobic capacity
      had no impact on WD-induced hepatic steatosis; however, rats bred for low aerobic
      capacity developed greater hepatic inflammation, which was associated with
      reduced hepatic mitochondrial FAO and respiratory capacity and increased
      accumulation of cholesterol esters. These results confirm epidemiological reports
      that aerobic capacity impacts progression of liver disease and suggest that these
      effects are mediated through alterations in hepatic mitochondrial function.

PMID- 28504312
TI  - G-POEM with antro-pyloromyotomy for the treatment of refractory gastroparesis:
      mid-term follow-up and factors predicting outcome.
AB  - BACKGROUND: Gastric peroral endoscopic pyloromyotomy (G-POEM) was introduced for
      treating refractory gastroparesis. AIM: To present a series of patients focussed
      on clinical mid-term efficacy and predictive outcomes factors. METHODS: This was
      a single centre study of 29 patients operated on between January 2014 and April
      2016, with disturbed gastric emptying scintigraphy (GES) and/or elevated
      Gastroparesis Cardinal Symptoms Index (GCSI). The procedures were performed as
      previously described. The primary endpoint was the efficacy at 3 and 6 months,
      based on GCSI and symptoms. The secondary endpoints were GES evolution, procedure
      reproducibility and safety, and identification of predictive factors for success.
      RESULTS: There were 10 men, 19 women (mean age 52.8+/-18). The technical success
      rate was 100% (average 47 minutes). There were two complications managed
      conservatively: one bleeding and one abscess. The median follow-up was 10+/-6.4
      months. The clinical success rate was 79% at 3 months, 69% at 6 months, with a
      significant decrease in the mean GCSI compared to pre-operatively (3.3+/-0.9 vs
      1+/-1.2 and 1.1+/-0.9 respectively). The GES (n=23) normalised in 70% of cases,
      with a significant improvement of the mean half emptying time and retention at 2
      hours, and a discordance in 21% of the cases. In univariate analysis, diabetes
      and female gender were significantly associated with risk of failure, but not
      confirmed in multivariate analysis. CONCLUSIONS: The mid-term efficacy of G-POEM
      reaches 70% at 6 months. The procedure remains reproducible and safe. Diabetes
      and female gender were predictive of failure.

PMID- 28504313
TI  - Ultrasound-Guided Fine-Needle Aspiration in the Neck Region Using an Optical See
      Through Head-Mounted Display: A Randomized Controlled Trial.
AB  - OBJECTIVES: The purpose of this study was to examine the feasibility of an
      optical see-through head-mounted display (OST-HMD) to improve ergonomics during
      ultrasound-guided fine-needle aspiration (FNA) in the neck region. METHODS: This
      randomized controlled study compared an OST-HMD with a normal ultrasound monitor
      during an ultrasound-guided FNA in the neck region. Patients with a neck tumor
      were recruited and randomized into one of two groups. Two practitioners performed
      ultrasound-guided FNA with or without the HMD, as indicated. An independent
      researcher measured the procedure time, the number and time of head movements, as
      well as the number of needle redirections. In addition, practitioners completed
      questionnaires after performing the FNA on each patient. RESULTS: In 93% of the
      sessions with the OST-HMD, practitioners performed ultrasound-guided FNA without
      turning the patients' heads. There was no difference in procedural time and
      number of needle redirections between the two groups. Results from the
      questionnaire revealed not only good wearability and low fatigue, but also the
      practitioners' preference for the HMD. CONCLUSIONS: The OST-HMD improved the
      practitioners' ergonomics and can be adopted for performing ultrasound-guided
      interventional procedures in clinical settings.

PMID- 28504314
TI  - Next step in antibiotic stewardship: Pharmacist-provided penicillin allergy
      testing.
AB  - WHAT IS KNOWN: Penicillin allergy limits therapeutic options for patients but
      often disappears over time, leaving patients erroneously labelled allergic and
      leading to the utilization of broad-spectrum and more expensive antibiotics.
      Penicillin allergy can be effectively assessed via skin testing. OBJECTIVE: To
      improve patient access to penicillin allergy testing by implementing a pharmacist
      provided service in a hospital setting. COMMENT: Beta-lactams remain a mainstream
      therapy for many infections due to their effectiveness, low side effects and
      affordability. Typically, patient access to penicillin allergy testing is limited
      by the availability of allergy specialists, who traditionally perform such
      testing. A pharmacist-provided penicillin allergy testing service was implemented
      at our hospital in 2015 and became a powerful antibiotic stewardship tool.
      Removing penicillin allergy from patient profiles significantly expanded
      therapeutic options, expedited discharges and reduced costs of care. WHAT IS NEW:
      Pharmacists can expand patient access to penicillin allergy testing. CONCLUSION:
      Pharmacist-provided penicillin allergy testing permitted optimized antibiotic
      treatment and expedited discharges.

PMID- 28504315
TI  - Media Reporting on Suicide: Evaluating the Effects of Including Preventative
      Resources and Psychoeducational Information on Suicide Risk, Attitudes,
      Knowledge, and Help-Seeking Behaviors.
AB  - We evaluated the effects of exposure to a suicide news article on a variety of
      outcome variables and whether adhering to one specific media guideline (i.e.,
      including psychoeducational information and preventative resources) buffered any
      of the negative effects of exposure. Participants were randomly assigned to read
      one of three articles and then asked to complete a battery of self-report
      questionnaires. Overall, we found no effect of exposure to a suicide news
      article, regardless of the inclusion of resources and information, with a few
      minor exceptions. Although researchers have demonstrated the effectiveness of
      media guidelines in the aggregate at reducing imitative suicidal behavior, it
      remains unclear which guidelines in particular are responsible for this effect.

PMID- 28504316
TI  - Rational design of a pH-insensitive cyan fluorescent protein CyPet2 based on the
      CyPet crystal structure.
AB  - The emission spectrum of widely used CyPet is pH-sensitive. In order to
      synthesize a pH-insensitive cyan fluorescent protein by rational design, we
      solved the crystal structures of CyPet under different pH conditions. The indole
      group of the CyPet chromophore adopts a cis-coplanar conformation in acidic and
      neutral conditions, while it converts to trans-coplanar under basic conditions.
      His148 and Glu222 play a vital role in this isomerization. The pH-sensitive
      chromophore isomerization and change in the emission spectrum can be explained by
      the coexistence of several different fluorescent states. We trap the chromophore
      in the trans conformation by A167I mutation (CyPet2), which also prevents the
      multiconformation of the seventh beta-strand. CyPet2 exhibits an unchanged
      emission spectral shape as a function of pH.

PMID- 28504317
TI  - Adrenal cortex reactivity in dairy cows differs between lactational stages and
      between different feeding levels.
AB  - Changes in ACTH challenge test characteristics in dairy cows changing their
      physiological status at different lactational stages and different feeding levels
      were not investigated in terms of repeatability yet. In 23 multiparous Holstein
      cows (10 cows fed a sole fresh herbage diet without concentrate, 13 cows fed with
      concentrate), three ACTH challenge tests were performed: once during pregnancy
      shortly prior to drying off (T1), and in week 3 (T2) and 8 (T3) after
      parturition. Test characteristics were correlated to performance and metabolic
      parameters: DMI, BW, energy balance (EB), plasma concentrations of free fatty
      acids (NEFA) and beta-hydroxybutyrate (BHB). Basal plasma cortisol concentrations
      were higher at T1 compared with T2 and T3 (p < .05). The adrenal cortex
      sensitivity (expressed as total AUC (AUCt ) of cortisol response after ACTH
      application) was lowest at T2 compared with T1 and T3 (p < .05). Ranking of the
      individual animals' responses was not repeatable between time points of the ACTH
      tests. Enhancing the energy deficiency during early lactation by omission of
      concentrate did not affect baseline cortisol concentrations in plasma, but
      decreased peak height at T2 (p < .05). Baseline plasma cortisol concentrations
      were positively correlated with cortisol peak values after ACTH application,
      previous lactation performance, milk yield and BW (p < .05). The AUCt was
      positively correlated with baseline cortisol concentrations, EB and DMI. Cortisol
      release after ACTH injection was lower in animals with high plasma concentrations
      of NEFA, BHB and with higher contents of fat and free fatty acids in milk (p <
      .05). Cortisol peak height after ACTH administration was higher in cows with a
      more positive EB, higher DMI and lower plasma concentrations of NEFA and BHB. In
      summary, cortisol responses to ACTH challenges in this study were not repeatable
      in dairy cows changing their physiological status.

PMID- 28504318
TI  - Antifungal prophylaxis in newly diagnosed AML patients-Adherence to guidelines
      and feasibility in a real life setting.
AB  - Antifungal posaconazole prophylaxis for AML patients receiving induction
      chemotherapy has been routine at our centre since 2009. This retrospective study
      examined the feasibility and practicability of our prophylaxis guidelines in
      clinical practice. Data sets of 90 patients undergoing induction-chemotherapy for
      AML between 2011 and 2014 were evaluated regarding adherence to local guidelines
      for the administration of antifungal prophylaxis with posaconazole. 75.5% of the
      90 patients received posaconazole prophylaxis. All but eight patients received
      the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan
      measured twice weekly. Contradicting our guidelines, 89.70% of patients received
      concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis
      discontinued and started empirical antifungal treatment in the absence of
      diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven,
      probable and possible) with 7.35% of infections being classified as proven or
      probable. Although limited by a small sample size, our study demonstrates the
      feasibility of local guidelines in a real life setting and outlines areas for
      improvement in both guidelines and clinical practice. We also highlight the
      importance of ensuring awareness of guidelines and raise questions about a
      uniform approach to antifungal prophylaxis in AML patients.

PMID- 28504319
TI  - Biological response of commercially available different tricalcium silicate-based
      cements and pozzolan cement.
AB  - This study evaluated four root repair materials for cytotoxicity and cell
      attachment in vitro. Cell viability was determined at 24 hr, 3 days and 7 days by
      using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide
      (XTT) assay with material extracts. Cell adhesion was examined with a scanning
      electron microscope on the surface of materials at 24 and 48 hr. Angelus MTA
      displayed the lowest cell viabilities at all-day incubations. Endocem had high
      biocompatibility on the first day. After culturing for 3 days and 7 days, the
      cell viabilities of Biodentine, Endocem and MM-MTA had similar results, and their
      cell viability was significantly higher than that of Angelus. No definite
      relation was found between the incubation time and the relative cell viability in
      any group. In scanning electron micrographs, the cells were attached to the
      material surface for all materials, although the cells in the Biodentine group
      were attached better than the other groups on the second day. Cell viability and
      cell attachment was lower in the Angelus group. Endocem, Biodentine and MM-MTA
      were similar in biocompatibility and cytotoxicity.

PMID- 28504320
TI  - Photosensitization Priming of Tumor Microenvironments Improves Delivery of
      Nanotherapeutics via Neutrophil Infiltration.
AB  - Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles
      (NPs). This study shows that direct priming of a tumor tissue using
      photosensitization rapidly activates neutrophil infiltration that mediates
      delivery of nanotherapeutics into the tumor. A drug delivery platform is
      comprised of NPs coated with anti-CD11b antibodies (Abs) that target activated
      neutrophils. Intravital microscopy demonstrates that the movement of anti-CD11b
      Abs-decorated NPs (NPs-CD11b) into the tumor is mediated by neutrophil
      infiltration induced by photosensitization (PS) because the systemic depletion of
      neutrophils completely abolishes the nanoparticle tumor deposition. The
      neutrophil uptake of NPs does not alter neutrophil activation and transmigration.
      For cancer therapy in mice, tumor PS and photothermal therapy of anti-CD11b Abs
      linked gold nanorods (GNRs-CD11b) are combined to treat the carcinoma tumor. The
      result indicates that neutrophil tumor infiltration enhances nanoparticle cancer
      therapy. The findings reveal that promoting tumor infiltration of neutrophils by
      manipulating tumor microenvironments could be a novel strategy to actively
      deliver nanotherapeutics in cancer therapies.

PMID- 28504321
TI  - Hemodynamic responses and plasma phenylephrine concentrations associated with
      intranasal phenylephrine in children.
AB  - INTRODUCTION: Intranasal phenylephrine, an alpha-1 adrenergic agonist, causes
      vasoconstriction of the nasal mucosa and is used to reduce bleeding associated
      with nasotracheal intubation or endoscopic sinus surgery. The purpose of this
      study was to describe the hemodynamic effects associated with plasma
      phenylephrine concentrations following topical intranasal administration of 0.25%
      and 0.5% phenylephrine in children. METHODS: After Institutional Review Board and
      parental approval, 77 children between the ages of 2 and 12 years were studied in
      a prospective, double-blind manner and randomized into three groups. Group 1
      received intranasal saline, while groups 2 and 3 received 0.1 mL/kg of 0.25% or
      0.5% phenylephrine, respectively. All received the same anesthetic of halothane,
      N2 O, O2 , and vecuronium. After inhalation induction, endtidal halothane and
      PaCO2 were maintained at 1.5% and 35 mm Hg, respectively. Heart rate and rhythm,
      systolic, diastolic, and mean, noninvasive arterial blood pressures were recorded
      and venous blood was obtained for measurement of plasma phenylephrine
      concentration by high-performance liquid chromatography at baseline and at 2, 5,
      10, and 20 minutes following intranasal spray application of the study drug.
      Nasotracheal intubation was performed immediately following the 5-minute
      measurements, and the presence of bleeding was assessed. Hemodynamic data were
      compared by analysis of variance for repeated measures. Bleeding and arrhythmia
      incidence among groups were analyzed using chi-squared tests. Phenylephrine
      levels were correlated with hemodynamic values via regression analysis. RESULTS:
      Fifty-two patients received intranasal phenylephrine. Increases in blood pressure
      correlated with increasing plasma phenylephrine concentration. Systolic blood
      pressure increased 8%, and mean blood pressure increased 14%, which were
      statistically significant but clinically insignificant. Heart rate did not
      change, and the incidence of arrhythmia was low and similar among groups.
      Bleeding following nasotracheal intubation was less frequent in Group 3 (11/27
      subjects) than in Group 1 (17/25). Peak plasma phenylephrine concentrations were
      observed by 14+/-7 minutes following intranasal administration, and were highly
      variable among individuals (37.8+/-39.7 and 49.6+/-93.9 ng/mL [mean+/-SD] in
      Groups 2 and 3). DISCUSSION: Administration of intranasal phenylephrine, 0.25%
      and 0.50%, results in rapid but highly variable systemic absorption that is
      associated with mild increases of blood pressure that are clinically
      insignificant. Bleeding associated with nasotracheal intubation was less
      following administration of 0.5% intranasal phenylephrine than following
      intranasal saline.

PMID- 28504322
TI  - Racial differences in the pain management of children recovering from anesthesia.
AB  - BACKGROUND: When pain management has been studied in settings such as pediatric
      emergency departments, racial disparities have been clearly identified. To our
      knowledge, this has not been studied in the pediatric perioperative setting. We
      sought to determine whether there are differences based on race in the
      administration of analgesia to children suffering from pain in the postanesthesia
      care unit. METHODS: This is a prospective, observational, study of 771 children
      aged 4-17 years who underwent elective outpatient surgery. Racial differences in
      probability of receiving analgesia for pain in the recovery room were assessed
      using bivariable and multivariable logistic regression analyses. RESULTS: A total
      of 294 children (38.2%) received at least one class of analgesia (opioid or
      nonopioid); while 210 (27.2%) received intravenous (i.v.) opioid analgesia in the
      recovery room. Overall postanesthesia care unit analgesia utilization was similar
      between white and minority children (white children 36.8% vs minority children
      43.4%, OR 1.3; 95% CI=0.92-1.89; P=.134). We found no significant difference by
      racial/ethnic group in the likelihood of a child receiving i.v. opioid for severe
      postoperative pain (white children 76.0% vs 85.7%, OR 1.89; 95% CI=0.37-9.67;
      P=.437). However, minority children were more likely to receive i.v. opioid
      analgesia than their white peers (white children 24.5% vs minority children
      34.2%, OR 1.5; 95% CI=1.04-2.2; P=.03). On multivariable analysis, minority
      children had a 63% higher adjusted odds of receiving i.v. opioids in the recovery
      room (OR=1.63; 95% CI, 1.05-2.62; P=.03). CONCLUSIONS: Receipt of analgesia for
      acute postoperative pain was not significantly associated with a child's race.
      Minority children were more likely to receive i.v. opioids for the management of
      mild pain.

PMID- 28504323
TI  - The Systemic Interaction of Attachment on Psychophysiological Arousal in Couple
      Conflict.
AB  - Attachment in adult romantic relationships has long been linked to conflict
      styles. Psychophysiological measures have provided additional insight into this
      association by accessing less conscious and controlled responses to conflict. The
      aim of this study was to explore the relationship between attachment anxiety,
      attachment avoidance, and the interaction between attachment styles on skin
      conductance responses during conflict and recovery from conflict. Using dyadic
      analysis of 50 heterosexual couples, we found evidence of a systemic effect of
      attachment, where psychophysiological arousal increased when one partner had
      higher levels of attachment anxiety and the other partner had higher levels of
      attachment avoidance. Attachment avoidance was also negatively associated with
      increased levels of arousal. Relationship and clinical implications of these
      findings are discussed.

PMID- 28504324
TI  - Electromagnetic Fields, Pulsed Radiofrequency Radiation, and Epigenetics: How
      Wireless Technologies May Affect Childhood Development.
AB  - Mobile phones and other wireless devices that produce electromagnetic fields
      (EMF) and pulsed radiofrequency radiation (RFR) are widely documented to cause
      potentially harmful health impacts that can be detrimental to young people. New
      epigenetic studies are profiled in this review to account for some
      neurodevelopmental and neurobehavioral changes due to exposure to wireless
      technologies. Symptoms of retarded memory, learning, cognition, attention, and
      behavioral problems have been reported in numerous studies and are similarly
      manifested in autism and attention deficit hyperactivity disorders, as a result
      of EMF and RFR exposures where both epigenetic drivers and genetic (DNA) damage
      are likely contributors. Technology benefits can be realized by adopting wired
      devices for education to avoid health risk and promote academic achievement.

PMID- 28504325
TI  - Therapeutic ultrasound for venous leg ulcers.
AB  - BACKGROUND: Venous leg ulcers are a type of chronic, recurring, complex wound
      that is more common in people aged over 65 years. Venous ulcers pose a
      significant burden to patients and healthcare systems. While compression therapy
      (such as bandages or stockings) is an effective first-line treatment, ultrasound
      may have a role to play in healing venous ulcers. OBJECTIVES: To determine
      whether venous leg ulcers treated with ultrasound heal more quickly than those
      not treated with ultrasound. SEARCH METHODS: We searched the Cochrane Wounds
      Specialised Register (searched 19 September 2016); the Cochrane Central Register
      of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 8); Ovid MEDLINE
      (including In-Process & Other Non-Indexed Citations, MEDLINE Daily and Epub Ahead
      of Print) (1946 to 19 September 2016); Ovid Embase (1974 to 19 September 2016);
      and EBSCO CINAHL Plus (1937 to 19 September 2016). We also searched three
      clinical trials registries and the references of included studies and relevant
      systematic reviews. There were no restrictions based on language, date of
      publication or study setting. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) that compared ultrasound with no ultrasound. Eligible non-ultrasound
      comparator treatments included usual care, sham ultrasound and alternative leg
      ulcer treatments. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed the search results and selected eligible studies. Details from included
      studies were summarised using a data extraction sheet, and double-checked. We
      attempted to contact trial authors for missing data. MAIN RESULTS: Eleven trials
      are included in this update; 10 of these we judged to be at an unclear or high
      risk of bias. The trials were clinically heterogeneous with differences in
      duration of follow-up, and ultrasound regimens. Nine trials evaluated high
      frequency ultrasound; seven studies provided data for ulcers healed and two
      provided data on change in ulcer size only. Two trials evaluated low frequency
      ultrasound and both reported ulcers healed data.It is uncertain whether high
      frequency ultrasound affects the proportion of ulcers healed compared with no
      ultrasound at any of the time points evaluated: at seven to eight weeks (RR 1.21,
      95% CI 0.86 to 1.71; 6 trials, 678 participants; low quality evidence -
      downgraded once for risk of bias and once for imprecision); at 12 weeks (RR 1.26,
      95% CI 0.92 to 1.73; 3 trials, 489 participants; moderate quality evidence -
      downgraded once for imprecision); and at 12 months (RR 0.93, 95% CI 0.73 to 1.18;
      1 trial, 337 participants; low quality evidence - downgraded once for unclear
      risk of bias and once for imprecision).One trial (92 participants) reported that
      a greater percentage reduction in ulcer area was achieved at four weeks with high
      frequency ultrasound, while another (73 participants) reported no clear
      difference in change in ulcer size at seven weeks. We downgraded the level of
      this evidence to very low, mainly for risk of bias (typically lack of blinded
      outcome assessment and attrition) and imprecision.Data from one trial (337
      participants) suggest that high frequency ultrasound may increase the risk of non
      serious adverse events (RR 1.29, 95% CI 1.02 to 1.64; moderate quality evidence -
      downgraded once for imprecision) and serious adverse events (RR 1.21, 95% CI 0.78
      to 1.89; moderate quality evidence downgraded once for imprecision).It is
      uncertain whether low frequency ultrasound affects venous ulcer healing at eight
      and 12 weeks (RR 3.91, 95% CI 0.47 to 32.85; 2 trials, 61 participants; very low
      quality evidence (downgraded for risk of bias and imprecision)).High-frequency
      ultrasound probably makes little or no difference to quality of life (moderate
      quality evidence, downgraded for imprecision). The outcomes of adverse effects,
      quality of life and cost were not reported for low-frequency ultrasound
      treatment. AUTHORS' CONCLUSIONS: It is uncertain whether therapeutic ultrasound
      (either high or low frequency) improves the healing of venous leg ulcers. We
      rated most of the evidence as low or very low quality due to risk of bias and
      imprecision.

PMID- 28504328
TI  - Response to Miller and Johnston.

PMID- 28504326
TI  - Preoperative colonization in pediatric cardiac surgery and its impact on
      postoperative infections.
AB  - BACKGROUND: Patients with congenital heart defects are frequently hospitalized
      before surgery. This exposes them to a high risk for pathogen colonization. There
      are limited data on colonization prevalence in the pediatric cardiac population,
      and limited data concerning its potential role in the risk of developing
      infections after cardiac surgery. AIM: This study aimed to verify the impact of
      preoperative colonization on postoperative infections in a population of
      pediatric cardiac surgery patients coming from Italy and developing countries.
      METHODS: This was a retrospective study conducted in all the patients aged <=18
      years who underwent pediatric open-heart surgery in the year 2015. Clinical data
      were retrieved from the institutional database for cardiac surgery patients. Data
      on swab cultures were retrieved from the laboratory database. Swab colonization
      was tested for association with infection and other outcomes. RESULTS: Among 169
      children who performed the screening for pathogen colonization, 50% had at least
      one positive swab. Italian patients were (P=.001) less likely to be colonized
      with respect to foreign patients (relative risk 0.17, 95% CI 0.09-0.35).
      Postoperative infections in colonized patients occurred at a similar rate as in
      noncolonized patients (relative risk 1.24, 95% CI 0.64-2.39; P=.532). Colonized
      patients had a preoperative stay (P=.021) longer than noncolonized patients (mean
      difference 2 days, 95% CI 0.3-3.8 days). CONCLUSION: The results of our study
      suggest that the impact of preoperative colonization on outcome and postoperative
      infections may be negligible; larger series are required to clearly define this
      issue.

PMID- 28504329
TI  - Rediscovering the ritual technology of the placebo effect in analytical
      psychology.
AB  - Technology, viewed more generally, is a collection of skills and methods that are
      used to accomplish an objective of some kind. Modernity has produced many kinds
      of ever-expanding new technologies, but it is also evident that technologies can
      be lost or fall out of use. A cross-cultural survey of ritual reveals a rather
      startling observation: that while developed nations often exceed other cultures
      in terms of material technology, they often pale by comparison in their use of
      ritual technology. In this essay we will see how ritual is a powerful sort of
      technology that developed nations have mostly allowed to drift out of regular,
      vigorous use, despite its numerous psychological and biological effects. This
      tendency has left one of the rituals we still have - psychotherapy itself - to be
      bereft of some of the typical tools for concretizing the symbolic in recurrent
      patterns around the world. Jung himself could be accused of being somewhat anti
      ritual himself, enmeshed as he was in the post-Protestant, post-Enlightenment
      cultural environment that defines the West in many ways. But these under-utilized
      elements of ritual technology may be a natural fit for Jungian therapy due to its
      use of symbols.

PMID- 28504327
TI  - Preferences for prenatal diagnosis of sickle-cell disorder: A discrete choice
      experiment comparing potential service users and health-care providers.
AB  - BACKGROUND: Non-invasive prenatal diagnosis (NIPD) for sickle-cell disorder (SCD)
      is moving closer to implementation and studies considering stakeholder
      preferences are required to underpin strategies for offering NIPD in clinical
      practice. OBJECTIVE: Determine service user and provider preferences for key
      attributes of prenatal diagnostic tests for SCD and examine views on NIPD.
      METHOD: A questionnaire that includes a discrete choice experiment was used to
      determine the preferences of service users and providers for prenatal tests that
      varied across three attributes: accuracy, time of test and risk of miscarriage.
      RESULTS: Adults who were carriers of SCD or affected with the condition (N=67)
      were recruited from haemoglobinopathy clinics at two maternity units. Health
      professionals, predominately midwives, who offer antenatal care (N=62) were
      recruited from one maternity unit. No miscarriage risk was a key driver of
      decision making for both service users and providers. Service providers placed
      greater emphasis on accuracy than service users. Current uptake of invasive tests
      was 63%, whilst predicted uptake of NIPD was 93.8%. Many service users (55.4%)
      and providers (52.5%) think pressure to have prenatal testing will increase when
      NIPD for SCD becomes available. CONCLUSIONS: There are clear differences between
      service users and health professionals' preferences for prenatal tests for sickle
      cell disorder. The safety of NIPD is welcomed by parents and uptake is likely to
      be high. To promote informed choice, pretest counselling should be balanced and
      not exclusively focused on test safety. Counselling strategies that are sensitive
      to feelings of pressure to test will be essential.

PMID- 28504330
TI  - Analytical practice: do the new technologies have an impact?
AB  - Through commentary on four clinical vignettes, this article focuses on the
      anthropological transformations taking place in contemporary society, underlining
      their differences from the anthropologies of reference of the founding fathers of
      psychoanalysis. Hybridization between man and machine and the speeding up and
      alteration of communications which the new technologies promote are now crucial
      issues facing psychoanalysis. Social media and a 24/7 internet connection have
      produced deep changes in the way people live and perceive relationships.
      Analytical practice is not exempt from such issues, which can be particularly
      insidious, often subtle and difficult to recognize, or even underestimated or
      ignored by psychoanalysts outright, in order to preserve the illusion of a
      complete understanding of what unfolds in the analytical space. The authors
      suggest that such transformations, by (partially) rendering inadequate the
      theoretical and technical corpus on which the various depth psychologies are
      founded, require personal engagement on the part of psychoanalysts in the search
      for new strategies to treat their patients, with the consequent abandonment of
      the 'certainties' offered by sclerotic models of clinical procedure.

PMID- 28504331
TI  - A response to Steve Myers: The transcendent function is different in kind.

PMID- 28504332
TI  - Guest editorial: Jung and technology.

PMID- 28504334
TI  - Advances in functional brain imaging technology and developmental neuro
      psychology: their applications in the Jungian analytic domain.
AB  - Analytical psychology shares with many other psychotherapies the important task
      of repairing the consequences of developmental trauma. The majority of analytic
      patients come from compromised early developmental backgrounds: they may have
      experienced neglect, abuse, or failures of empathic resonance from their carers.
      Functional brain imagery techniques including Quantitative Electroencephalogram
      (QEEG), and functional Magnetic Resonance Imagery (fMRI), allow us to track
      mental processes in ways beyond verbal reportage and introspection. This
      independent perspective is useful for developing new psychodynamic hypotheses,
      testing current ones, providing diagnostic markers, and monitoring treatment
      progress. Jung, with the Word Association Test, grasped these principles 100
      years ago. Brain imaging techniques have contributed to powerful recent advances
      in our understanding of neurodevelopmental processes in the first three years of
      life. If adequate nurturance is compromised, a range of difficulties may emerge.
      This has important implications for how we understand and treat our psychotherapy
      clients. The paper provides an overview of functional brain imaging and advances
      in developmental neuropsychology, and looks at applications of some of these
      findings (including neurofeedback) in the Jungian psychotherapy domain.

PMID- 28504335
TI  - Tele-analysis: the use of media technology in psychotherapy and its impact on the
      therapeutic relationship.
AB  - A growing number of approaches in psychotherapy make use of internet- and other
      media-based interactions. This paper discusses the impact on the therapist-client
      relationship of using media technology and gives an overview of the current state
      of the debate. It is suggested that the technical conditions of internet-based
      interactions produce new forms of social relationships that differ significantly
      from face-to-face-interactions and that unconscious, nonverbal cues get lost.
      Research on the therapeutic interaction making use of 'discourse linguistic'
      methods is presented. The loss of nonverbal cues has implications for
      psychotherapy in general and especially for the treatment of patients who have
      difficulties relying on a secure therapeutic relationship. Emotional security in
      interactional relationships is transmitted to a much greater extent by nonverbal
      cues than by verbal content; psychoanalytic methods are specialized to refer to
      this level of interaction. Two alternative scenarios are discussed based on the
      psychoanalytic theories of Winnicott and Lacan: the risk of an illusionary,
      idealized image of the other and the possibility that cyberspace can be used for
      psychological development as a transitional space.

PMID- 28504337
TI  - Archaic man meets a marvellous automaton: posthumanism, social robots,
      archetypes.
AB  - Posthumanism is associated with critical explorations of how new technologies are
      rewriting our understanding of what it means to be human and how they might alter
      human existence itself. Intersections with analytical psychology vary depending
      on which technologies are held in focus. Social robotics promises to populate
      everyday settings with entities that have populated the imagination for
      millennia. A legend of A Marvellous Automaton appears as early as 350 B.C. in a
      book of Taoist teachings, and is joined by ancient and medieval legends of
      manmade humanoids coming to life, as well as the familiar robots of modern
      science fiction. However, while the robotics industry seems to be realizing an
      archetypal fantasy, the technology creates new social realities that generate
      distinctive issues of potential relevance for the theory and practice of
      analytical psychology.

PMID- 28504338
TI  - Plasmonic-Based Electrochemical Impedance Imaging of Electrical Activities in
      Single Cells.
AB  - Studying electrical activities in cells, such as action potential and its
      propagation in neurons, requires a sensitive and non-invasive analytical tool
      that can image local electrical signals with high spatial and temporal
      resolutions. Here we report a plasmonic-based electrochemical impedance imaging
      technique to study transient electrical activities in single cells. The technique
      is based on the conversion of the electrical signal into a plasmonic signal,
      which is imaged optically without labels. We demonstrate imaging of the fast
      initiation and propagation of action potential within single neurons, and
      validate the imaging technique with the traditional patch clamp technique. We
      anticipate that the plasmonic imaging technique will contribute to the study of
      electrical activities in various cellular processes.

PMID- 28504340
TI  - A Single Spherical Assembly of Protein Amyloid Fibrils Formed by Laser Trapping.
AB  - Protein amyloids have received much attention owing to their correlation with
      serious diseases and to their promising mechanical and optical properties as
      future materials. Amyloid formation has been conducted by tuning temperature and
      chemical conditions, so that its nucleation and the following growth are analyzed
      as ensemble dynamics. A single spherical assembly of amyloid fibrils of
      cytochrome c domain-swapped dimer was successfully generated upon laser trapping.
      The amyloid fibrillar structure was confirmed by fluorescence characterization
      and electron microscopy. The prepared spheres were further manipulated
      individually in solution to fabricate a three-dimensional microstructure and a
      line pattern. Amyloid formation dynamics and amyloid-based microstructure
      fabrication are demonstrated based on direct observation of a single spherical
      assembly, which foresees a new approach in amyloid studies.

PMID- 28504339
TI  - Mexneurin is a novel precursor of peptides in the central nervous system of
      rodents.
AB  - Endomorphins (EMs) have been proposed as the endogenous ligand agonists of the MU
      opioid receptor; however, no propeptide precursor protein for EMs has been
      identified. Here, to identify the presumed precursor of EMs, we designed an
      immunoscreening assay using specific affinity-purified rabbit antisera raised
      against synthetic EMs in a whole-mouse brain cDNA library. Following this
      approach, we identify a DNA sequence encoding a protein precursor, which we name
      proMexneurin, that contains three different peptide sequences: Mexneurin-1 (an EM
      like peptide), Mexneurin-2, and Mexneurin-3, a peptide which appears to be
      unrelated to EMs. RT-PCR analysis and in situ hybridization reveal a widespread
      distribution of proMexneurin mRNA throughout the mouse brain. Both Mexneurin-1
      and Mexneurin-3 peptides display biological activities in the mouse CNS.

PMID- 28504341
TI  - Breathing circuit compliance and accuracy of displayed tidal volume during
      pressure-controlled ventilation of infants: A quality improvement project.
AB  - INTRODUCTION: Anesthesia machines have evolved to deliver desired tidal volumes
      more accurately by measuring breathing circuit compliance during a preuse self
      test and then incorporating the compliance value when calculating expired tidal
      volume. The initial compliance value is utilized in tidal volume calculation
      regardless of whether the actual compliance of the breathing circuit changes
      during a case, as happens when corrugated circuit tubing is manually expanded
      after the preuse self-test but before patient use. We noticed that the anesthesia
      machine preuse self-test was usually performed on nonexpanded pediatric circuit
      tubing, and then the breathing circuit was subsequently expanded for clinical
      use. We aimed to demonstrate that performing the preuse self-test in that manner
      could lead to incorrectly displayed tidal volume on the anesthesia machine
      monitor. The goal of this quality improvement project was to change the usual
      practice and improve the accuracy of displayed tidal volume in infants undergoing
      general anesthesia. METHODS: There were four stages of the project: (i) gathering
      baseline data about the performance of the preuse self-test and using infant and
      adult test lungs to measure discrepancies of displayed tidal volumes when
      breathing circuit compliance was changed after the initial preuse self-test; (ii)
      gathering clinical data during pressure-controlled ventilation comparing
      anesthesia machine displayed tidal volume with actual spirometry tidal volume in
      patients less than 10 kg before (machine preuse self-test performed while the
      breathing circuit was nonexpanded) and after an intervention (machine preuse self
      test performed after the breathing circuit was fully expanded); (iii) performing
      department-wide education to help implement practice change; (iv) gathering
      postintervention data to determine the prevalence of proper machine preuse self
      test. RESULTS: At constant pressure-controlled ventilation through fully expanded
      circuit tubing, displayed tidal volume was 83% greater in the infant test lung
      (mean+/-SD TV 15+/-5 vs 9+/-4 mL; mean [95% CI] difference=6.3 [5.6, 7.1] mL,
      P<.0001) and 3% greater in the adult test lung (245+/-74 vs 241+/-72 mL;
      difference=5 [1, 10] mL, P=.0905) when circuit compliance had been measured with
      nonexpanded tubing compared to when circuit compliance was measured with fully
      expanded tubing. The clinical data in infants demonstrated that displayed tidal
      volume was 41% greater than actual tidal volume (difference of 10.4 [8.6, 12.2]
      mL) when the circuit was expanded after the preuse self-test (preintervention)
      and 7% greater (difference of 2.5 [0.7, 4.2] mL) in subjects when the circuit was
      expanded prior to the preuse self-test (postintervention) (P<.0001). Clinical
      practice was changed following an intervention of departmental education: the
      preuse self-test was performed on expanded circuit tubing 11% of the time prior
      to the intervention and 100% following the intervention. CONCLUSION: Performing a
      preuse self-test on a nonexpanded pediatric circuit that is then expanded leads
      to falsely elevated displayed tidal volume in infants less than 10 kg during
      pressure-controlled ventilation. Overestimation of reported tidal volume can be
      avoided by expanding the breathing circuit tubing to the length which will be
      used during a case prior to performing the anesthesia machine preuse self-test.
      After department-wide education and implementation, performing a correct preuse
      self-test is now the standard practice in our cardiac operating rooms.

PMID- 28504342
TI  - Sudden death in a pediatric heart transplant recipient with peripheral
      eosinophilia and eosinophilic myocardial infiltrates.
AB  - Eosinophilia has been rarely reported in pediatric heart transplant recipients
      and has been suggested to play a role in graft rejection. We report a case of a
      young female patient with peripheral blood eosinophilia who died suddenly 2 years
      following ABO-incompatible heart transplantation. She was found at autopsy to
      have myocardial infiltration of not only T-lymphocytes and macrophages expected
      in acute cellular rejection but also of eosinophils, B-lymphocytes, and plasma
      cells indicating myocarditis.

PMID- 28504343
TI  - Gas Diffusion in the CNS.
AB  - Gases have been long known to have essential physiological functions in the CNS
      such as respiration or regulation of vascular tone. Since gases have been
      classically considered to freely diffuse, research in gas biology has so far
      focused on mechanisms of gas synthesis and gas reactivity, rather than gas
      diffusion and transport. However, the discovery of gas pores during the last two
      decades and the characterization of diverse diffusion patterns through different
      membranes has raised the possibility that modulation of gas diffusion is also a
      physiologically relevant parameter. Here we review the means of gas movement into
      and within the brain through "free" diffusion and gas pores, notably aquaporins,
      discussing the role that gas diffusion may play in the modulation of gas
      function. We highlight how diffusion is relevant to neuronal signaling, volume
      transmission, and cerebrovascular control in the case of NO, one of the most
      extensively studied gases. We point out how facilitated transport can be
      especially relevant for gases with low permeability in lipid membranes like NH3
      and discuss the possible implications of NH3 -permeable channels in physiology
      and hyperammonemic encephalopathy. We identify novel research questions about how
      modulation of gas diffusion could intervene in CNS pathologies. This emerging
      area of research can provide novel and interesting insights in the field of gas
      biology.

PMID- 28504346
TI  - Harvesting and blending options for lower alcohol wines: a sensory and chemical
      investigation.
AB  - BACKGROUND: Lower alcohol wines often have a poor reputation among consumers, in
      part due to their unsatisfactory flavours such as reduced overall aroma intensity
      or herbaceous characters. The aim of this study, performed on Verdelho and Petit
      Verdot, was to quantify the effectiveness of a monovarietal blend in which wines
      made from less ripe grapes were blended with an equivalent volume of a wine
      vinified from riper fruit to produce wines with a lower alcohol content and
      desirable ripe fruit flavours. RESULTS: Eleven and 13 attributes, for Verdelho
      and Petit Verdot, respectively, were selected during sensory descriptive
      analysis. Intensities of perceived 'acidity', 'sweetness' and 'alcohol'
      attributes were significantly different (P <= 0.05) between the blend (8.8 +/-
      0.1% v/v) and mature Verdelho (10.3 +/- 0.1% v/v) wines, while no significant
      differences were found between the Petit Verdot blend (11.0 +/- 0.1% v/v) and
      mature (12.6 +/- 0.2% v/v) treatments. Volatile composition of wines was assessed
      using HS-SPME-GC-MS. Partial least square regression suggested relationships
      between sensory descriptors and chemical attributes in the wines, as well as the
      modifications of sensory and compositional profiles following blending.
      CONCLUSIONS: The blending practice described allowed the production of wines with
      lower alcohol content while retaining similar sensory profiles of the later
      harvested, riper fruit wines. (c) 2017 Society of Chemical Industry.

PMID- 28504344
TI  - Following Rapoport's Rule: the geographic range and genome size of bacterial taxa
      decline at warmer latitudes.
AB  - We sought to test whether stream bacterial communities conform to Rapoport's
      Rule, a pattern commonly observed for plants and animals whereby taxa exhibit
      decreased latitudinal range sizes closer to the equator. Using a DNA sequencing
      approach, we explored the biogeography of biofilm bacterial communities in 204
      streams across a ~1000 km latitudinal gradient. The range sizes of bacterial taxa
      were strongly correlated with latitude, decreasing closer to the equator, which
      coincided with a greater than fivefold increase in bacterial taxonomic richness.
      The relative richness and range size of bacteria were associated with spatially
      correlated variation in temperature and rainfall. These patterns were observed
      despite enormous variability in catchment environmental characteristics. Similar
      results were obtained when restricting the same analyses to native forest
      catchments, thereby controlling for spatial biases in land use. We analysed
      genomic data from ~500 taxa detected in this study, for which data were available
      and found that bacterial communities at cooler latitudes also tended to possess
      greater potential metabolic potential. Collectively, these data provide the first
      evidence of latitudinal variation in the range size distributions of freshwater
      bacteria, a trend which may be determined, in part, by a trade-off between
      bacterial genome size and local variation in climatic conditions.

PMID- 28504347
TI  - A rapid method to screen poisoning causative agents in an acute care hospital in
      Japan.
AB  - WHAT IS KNOWN AND OBJECTIVE: A simple, rapid analysis is required to
      simultaneously analyse medicinal toxicants in emergency medical care. In this
      regard, the analysis of blood samples by LC-MS/MS equipped with a spin column,
      involving a rapid, simple pretreatment, has attracted attention. In this study,
      sample pretreatment using a Monospin C18 column was performed to screen 11
      medicinal toxicants in blood samples by LC-MS/MS. METHODS: Serum samples
      supplemented with 11 medical toxicants-acetaminophen, salicylic acid, nitrazepam,
      diphenhydramine, bromvalerylurea, phenobarbital, amitriptyline, risperidone,
      fenitrothion, malathion and methomyl-were pretreated with the Monospin C18 column
      according to Pretreatment I and Pretreatment II, followed by LC-MS/MS analysis.
      RESULTS AND DISCUSSION: All toxicants were not detected by a single pretreatment
      method but were detected by two pretreatment methods. According to Pretreatment
      I, 10 medicinal toxicants-excluding salicylic acid-were detected. The recovery
      rates of all medicinal toxicants, except acetaminophen and methomyl, were greater
      than or equal to 80%. Salicylic acid was detected by Pretreatment II, with a
      recovery rate of 57.1%. Although the coefficient of variation was less than that
      reported in previous methods employing SPE, the recovery rates were better
      possibly because of the simultaneous adsorption of water- and lipid-soluble
      substances and evaporation by drying. WHAT IS NEW AND CONCLUSION: As LC-MS/MS
      analysis using Monospin C18 can simultaneously and rapidly screen several
      medicinal toxicants present in blood samples, it is expected to be highly
      suitable for clinical settings.

PMID- 28504348
TI  - Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability
      and In Vivo Efficacy.
AB  - In this study, antimicrobial polymers are synthesized by the organocatalytic ring
      opening polymerization of an eight-membered heterocyclic carbonate monomer that
      is subsequently quaternized with methyl iodide. These polymers demonstrate
      activity against clinically relevant Gram-positive Staphylococcus epidermidis and
      Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa,
      and fungus Candida albicans with fast killing kinetics. Importantly, the polymer
      efficiently inhibits biofilm growth and lyses existing biofilm, leading to a
      reduction in biomass and cell viability. In addition, the macromolecular
      antimicrobial is less likely to induce resistance as it acts via a membrane-lytic
      mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0
      +/- 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream
      infection mouse model, the polymer removes bacteria from the blood more rapidly
      than the antibiotic Augmentin. At the effective dose, the polymer treatment does
      not damage liver and kidney tissues or functions. In addition, blood electrolyte
      balance remains unchanged after the treatment. The low cost of starting
      materials, ease of synthesis, nontoxicity, broad spectrum activity with fast
      killing kinetics, and in vivo antimicrobial activity make these macromolecular
      antimicrobials ideal candidates for prevention of sepsis and treatment of
      infections.

PMID- 28504349
TI  - Polysome profiling of mAb producing CHO cell lines links translational control of
      cell proliferation and recombinant mRNA loading onto ribosomes with global and
      recombinant protein synthesis.
AB  - mRNA translation is a key process determining growth, proliferation and duration
      of a Chinese hamster ovary (CHO) cell culture and influences recombinant protein
      synthesis rate. During bioprocessing, CHO cells can experience stresses leading
      to reprogramming of translation and decreased global protein synthesis. Here we
      apply polysome profiling to determine reprogramming and translational
      capabilities in host and recombinant monoclonal antibody-producing (mAb) CHO cell
      lines during batch culture. Recombinant cell lines with the fastest cell specific
      growth rates were those with the highest global translational efficiency.
      However, total ribosomal capacity, determined from polysome profiles, did not
      relate to the fastest growing or highest producing mAb cell line, suggesting it
      is the ability to utilise available machinery that determines protein synthetic
      capacity. Cell lines with higher cell specific productivities tended to have
      elevated recombinant heavy chain transcript copy numbers, localised to the
      translationally active heavy polysomes. The highest titre cell line was that
      which sustained recombinant protein synthesis and maintained high recombinant
      transcript copy numbers in polysomes. Investigation of specific endogenous
      transcripts revealed a number that maintained or reprogrammed into heavy
      polysomes, identifying targets for potential cell engineering or those with 5'
      untranslated regions that might be utilised to enhance recombinant transcript
      translation.

PMID- 28504351
TI  - Oligonucleotide probes functionalization of nanogap electrodes.
AB  - Nanogap electrodes have attracted a lot of consideration as promising platform
      for molecular electronic and biomolecules detection. This is mainly for their
      higher aspect ratio, and because their electrical properties are easily accessed
      by current-voltage measurements. Nevertheless, application of standard current
      voltages measurements used to characterize nanogap response, and/or to modify
      specific nanogap electrodes properties, represents an issue. Since the strength
      of electrical fields in nanoscaled devices can reach high values, even at low
      voltages. Here, we analyzed the effects induced by different methods of surface
      modification of nanogap electrodes, in test-voltage application, employed for the
      electrical detection of a desoxyribonucleic acid (DNA) target. Nanogap electrodes
      were functionalized with two antisymmetric oligo-probes designed to have 20
      terminal bases complementary to the edges of the target, which after
      hybridization bridges the nanogap, closing the electrical circuit. Two methods of
      functionalization were studied for this purpose; a random self-assembling of a
      mixture of the two oligo-probes (OPs) used in the platform, and a selective
      method that controls the position of each OP at selected side of nanogap
      electrodes. We used for this aim, the electrophoretic effect induced on
      negatively charged probes by the application of an external direct current
      voltage. The results obtained with both functionalization methods where
      characterized and compared in terms of electrode surface covering, calculated by
      using voltammetry analysis. Moreover, we contrasted the electrical detection of a
      DNA target in the nanogap platform either in site-selective and in randomly
      assembled nanogap. According to our results, a denser, although not selective
      surface functionalization, is advantageous for such kind of applications.

PMID- 28504352
TI  - Optimizing psychosocial adjustment after deep brain stimulation of the
      subthalamic nucleus in Parkinson's disease.

PMID- 28504350
TI  - The ArfGAP protein MoGlo3 regulates the development and pathogenicity of
      Magnaporthe oryzae.
AB  - The ADP ribosylation factor (Arf) and the coat protein complex I (COPI) are
      involved in vesicle transport. Together with GTPase-activating proteins (ArfGAPs)
      and guanine exchange factors (ArfGEFs) that regulate the activity of Arf, they
      govern vesicle formation, COPI trafficking and the maintenance of the Golgi
      complex. In an ongoing effort to study the role of membrane trafficking in
      pathogenesis of the rice blast fungus Magnaporthe oryzae, we identified MoGlo3 as
      an ArfGAP protein that is homologous to Glo3p of the budding yeast Saccharomyces
      cerevisiae. As suspected, MoGlo3 partially complements the function of yeast
      Glo3p. Consistent with findings in S. cerevisiae, MoGlo3 is localized to the
      Golgi, and that the localization is dependent on the conserved BoCCS domain. We
      found that MoGlo3 is highly expressed during conidiation and early infection
      stages and is required for vegetative growth, conidial production and sexual
      development. We further found that the DeltaMoglo3 mutant is defective in
      endocytosis, scavenging of the reactive oxygen species, and in the response to
      endoplasmic reticulum (ER) stress. The combined effects result in failed
      appressorium function and decreased pathogenicity. Moreover, we provided evidence
      showing that the domains including the GAP, BoCCS and GRM are all important for
      normal MoGlo3 functions. Our studies further illustrate the importance of normal
      membrane trafficking in the physiology and pathogenicity of the rice blast
      fungus.

PMID- 28504353
TI  - CMIP haploinsufficiency in two patients with autism spectrum disorder and co
      occurring gastrointestinal issues.
AB  - Autism spectrum disorder (ASD) is a genetically heterogeneous group of disorders
      characterized by impairments in social communication and restricted interests.
      Though some patients with ASD have an identifiable genetic cause, the cause of
      most ASD remains elusive. Many ASD susceptibility loci have been identified
      through clinical studies. We report two patients with syndromic ASD and
      persistent gastrointestinal issues who carry de novo deletions involving the CMIP
      gene detected by genome-wide SNP microarray and fluorescence in situ
      hybridization (FISH) analysis. Patient 1 has a 517 kb deletion within
      16q23.2q23.3 including the entire CMIP gene. Patient 2 has a 1.59 Mb deletion
      within 16q23.2q23.3 that includes partial deletion of CMIP in addition to 12
      other genes, none of which have a known connection to ASD or other clinical
      phenotypes. The deletion of CMIP is rare in general population and was not found
      among a reference cohort of approximately 12,000 patients studied in our
      laboratory who underwent SNP array analysis for various indications. A 280 kb de
      novo deletion containing the first 3 exons of CMIP was reported in one patient
      who also demonstrated ASD and developmental delay. CMIP has previously been
      identified as a susceptibility locus for specific language impairment (SLI). It
      is notable that both patients in this study had significant gastrointestinal
      issues requiring enteral feedings, which is unusual for patients with ASD, in
      addition to unusually elevated birth length, further supporting a shared
      causative gene. These findings suggest that CMIP haploinsufficiency is the likely
      cause of syndromic ASD in our patients.

PMID- 28504354
TI  - New methodology to reconstruct in 2-D the cuspal enamel of modern human lower
      molars.
AB  - OBJECTIVES: In the last years different methodologies have been developed to
      reconstruct worn teeth. In this article, we propose a new 2-D methodology to
      reconstruct the worn enamel of lower molars. Our main goals are to reconstruct
      molars with a high level of accuracy when measuring relevant histological
      variables and to validate the methodology calculating the errors associated with
      the measurements. METHODS: This methodology is based on polynomial regression
      equations, and has been validated using two different dental variables: cuspal
      enamel thickness and crown height of the protoconid. In order to perform the
      validation process, simulated worn modern human molars were employed. The
      associated errors of the measurements were also estimated applying methodologies
      previously proposed by other authors. RESULTS: The mean percentage error
      estimated in reconstructed molars for these two variables in comparison with
      their own real values is -2.17% for the cuspal enamel thickness of the protoconid
      and -3.18% for the crown height of the protoconid. This error significantly
      improves the results of other methodologies, both in the interobserver error and
      in the accuracy of the measurements. CONCLUSIONS: The new methodology based on
      polynomial regressions can be confidently applied to the reconstruction of cuspal
      enamel of lower molars, as it improves the accuracy of the measurements and
      reduces the interobserver error. The present study shows that it is important to
      validate all methodologies in order to know the associated errors. This new
      methodology can be easily exportable to other modern human populations, the human
      fossil record and forensic sciences.

PMID- 28504355
TI  - Home high-flow nasal cannula as a treatment for severe tracheomalacia: A
      pediatric case report.
AB  - Tracheomalacia refers to a softness of the tracheal cartilage that makes the
      airway more susceptible to collapse. In contrast to milder cases where
      conservative therapy is preferred, severe tracheomalacia is often a life
      threatening condition requiring more aggressive management. For children with
      this condition, a variety of treatment options are available. To our knowledge,
      this is the first report of home high-flow nasal cannula as an alternative
      therapy to continuous positive airway pressure (CPAP) and surgical procedures in
      a pediatric patient with severe extensive tracheomalacia.

PMID- 28504356
TI  - Bronchoscopy in children with tetralogy of fallot, pulmonary atresia, and major
      aortopulmonary collaterals.
AB  - OBJECTIVE: Children with Tetralogy of Fallot, Pulmonary Atresia, and Major
      Aortopulmonary Collaterals (TOF/PA/MAPCAs) undergoing unifocalization surgery are
      at risk for developing more postoperative respiratory complications than children
      undergoing other types of congenital heart surgery. Bronchoscopy is used in the
      perioperative period for diagnostic and therapeutic purposes. In this study, we
      describe bronchoscopic findings and identify factors associated with selection
      for bronchoscopy. DESIGN: Retrospective case-control. PATIENTS AND METHODS: All
      patients with TOF/PA/MAPCAs who underwent unifocalization surgery from September
      2005 through March 2016 were included. Patients who underwent bronchoscopy in the
      perioperative period were compared to a randomly selected cohort of 172 control
      patients who underwent unifocalization without bronchoscopy during the study
      period. RESULTS: Forty-three children underwent perioperative bronchoscopy at a
      median of 9 days postoperatively. Baseline demographics were similar in
      bronchoscopy patients and controls. Patients who underwent bronchoscopy were more
      likely to have a chromosome 22q11 deletion and were more likely have undergone
      unifocalization surgery without intracardiac repair. These patients had a longer
      duration of mechanical ventilation, ICU duration, and length of hospitalization.
      Abnormalities were detected on bronchoscopy in 35 patients (81%), and 20 (35%) of
      bronchoscopy patients underwent a postoperative intervention related to
      abnormalities identified on bronchoscopy. CONCLUSION: Bronchoscopy is a useful
      therapeutic and diagnostic instrument for children undergoing unifocalization
      surgery, capable of identifying abnormalities leading to an additional
      intervention in over one third of patients. Special attention should be given to
      children with a 22q11 deletion to expedite diagnosis and intervention for
      possible airway complications.

PMID- 28504357
TI  - A nationwide seroprevalence screening for West Nile virus and Tick-borne
      encephalitis virus in the population of Bulgaria.
AB  - To assess local circulation and risk for human infections with West Nile virus
      (WNV) and Tick-borne encephalitis virus (TBEV) in Bulgaria, a nationwide
      seroprevalence study was conducted. In total, 1451 residents of all 28 districts
      in Bulgaria were tested for WNV-specific and TBEV-specific IgG antibodies. The
      survey found overall seroprevalence of 1.5% and 0.6%, respectively. The highest
      WNV seroprevalence was found in Sofia Province and districts near the river
      Danube. TBEV circulation was detected among residents of six districts. The
      results showed that the two virus infections seem to be more wide-spread in the
      country as has been described.

PMID- 28504358
TI  - Randomized controlled trial of Functional Family Therapy for offending and
      antisocial behavior in UK youth.
AB  - BACKGROUND: Youth offending and antisocial behavior (ASB) are associated with low
      quality mental health and relationships and usually lead to poor adult
      functioning; they are very costly for society. Family interventions are effective
      in children but there are few reliably effective and inexpensive interventions
      for adolescents. Functional Family Therapy (FFT) is an evidence-based
      intervention but seldom tested outside the United States. METHODS: One hundred
      and eleven adolescents (10-17 years of age, M = 15.0, SD = 1.63) and their
      families were randomized to FFT + Management As Usual (MAU) (n = 65) or to MAU (n
      = 46). Assessments were made at baseline 6, and 18 months after randomization and
      included interviews and questionnaires of parenting behaviors, conduct disorders
      (CDs) and offending. Parent-child interaction was directly observed and police
      records obtained. TRIAL REGISTRATION: ISRCTN27650478. RESULTS: Eighty-nine (80%)
      were followed-up. In both groups, there were large reductions over time in all
      measures of offending and antisocial behavior (e.g. primary outcome p < 0.001),
      but no significant changes over time in parenting behavior or the parent-child
      relationship. However, there were no differences between intervention and control
      groups at 6 or 18 months on self-reported delinquency, police records of
      offending, symptoms or diagnoses of CDs, parental monitoring or supervision,
      directly observed child negative behavior, or parental positive or negative
      behavior. Against predictions, the intervention group showed lower levels of
      directly observed child positive behavior at 18 months compared to controls.
      CONCLUSIONS: In contrast to most previous trials of FFT, FFT+MAU did not lead to
      greater reductions in youth ASB and offending compared to MAU alone, and did not
      lead to improvements in parenting or the parent-child relationship. This may be
      because the trial was more rigorously conducted than prior studies; equally, the
      possibility that MAU was effective requires further research.

PMID- 28504359
TI  - Changing the paradigm for diagnostic MRI in pediatrics: Don't hold your breath.
AB  - Increasingly complex pediatric patients and improvements in technology warrant
      reevaluation of the risk associated with anesthesia for diagnostic imaging.
      Although magnetic resonance imaging is the imaging modality of choice for
      children given the potentially harmful effects of computerized tomography
      associated ionizing radiation, we dare to suggest that certain patients would
      benefit from the liberalization of our current standard. Incorporating the use of
      newer computerized tomography technology may improve safety for those that are
      already at higher risk for adverse events. Furthermore, magnetic resonance
      imaging is not risk-free-what is often overlooked is the need for controlled
      ventilation and breath-holding to minimize motion artifact. As physicians at the
      forefront of the development and sustainability of the perioperative surgical
      home, anesthesiologists must work to not only optimize patients preoperatively
      but should also act as gatekeepers for procedural safety.

PMID- 28504360
TI  - Oxygen extraction fraction mapping at 3 Tesla using an artificial neural network:
      A feasibility study.
AB  - PURPOSE: The oxygen extraction fraction (OEF) is an important biomarker for
      tissue-viability. MRI enables noninvasive estimation of the OEF based on the
      blood-oxygenation-level-dependent (BOLD) effect. Quantitative OEF-mapping is
      commonly applied using least-squares regression (LSR) to an analytical tissue
      model. However, the LSR method has not yet become clinically established due to
      the necessity for long acquisition times. Artificial neural networks (ANNs)
      recently have received increasing interest for robust curve-fitting and might
      pose an alternative to the conventional LSR method for reduced acquisition times.
      This study presents in vivo OEF mapping results using the conventional LSR and
      the proposed ANN method. METHODS: In vivo data of five healthy volunteers and one
      patient with a primary brain tumor were acquired at 3T using a gradient-echo
      sampled spin-echo (GESSE) sequence. The ANN was trained with simulated BOLD data.
      RESULTS: In healthy subjects, the mean OEF was 36 +/- 2% (LSR) and 40 +/- 1%
      (ANN). The OEF variance within subjects was reduced from 8% to 6% using the ANN
      method. In the patient, both methods revealed a distinct OEF hotspot in the tumor
      area, whereas ANN showed less apparent artifacts in surrounding tissue.
      CONCLUSION: In clinical scan times, the ANN analysis enables OEF mapping with
      reduced variance, which could facilitate its integration into clinical protocols.
      Magn Reson Med 79:890-899, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 28504362
TI  - Synthesis and structure elucidation of polyphenols containing the N'
      methyleneformohydrazide scaffold as aurora kinase inhibitors.

PMID- 28504361
TI  - Alterations of resting-state fMRI measurements in individuals with cervical
      dystonia.
AB  - Cervical dystonia (CD) is a neurological disorder with typical symptoms of
      involuntary and abnormal movements and postures of the head. CD-associated
      alterations of functional brain networks have not been well characterized.
      Previous studies of CD using resting-state functional MRI (rfMRI) are limited in
      two aspects: (i) the analyses were not directly focused on the functional brain
      network related to head movement and (ii) rfMRI measurements other than
      functional connectivity (FC) were not investigated. The present study examined
      alterations of FC in CD by capitalizing on newly identified brain regions
      supporting isometric head rotation (Prudente et al.: J Neurosci 35 (2015) 9163
      9172). In addition to FC, which only reflects inter-regional signal
      synchronization, local, or intraregional alterations were also examined using
      rfMRI measurements of the fractional amplitude of low-frequency fluctuations and
      regional homogeneity (ReHo). Finally, with alterations of different rfMRI
      measures identified, a support vector machine (SVM) learning algorithm was
      implemented for group classification. The results revealed both inter- (FC) and
      intra-regional (ReHo) alterations extensively distributed in both cortical and
      subcortical structures; and common alterations of these measures were identified
      bilaterally in the postcentral gyrus as well as in the basal ganglia and
      thalamus. Of the rfMRI features examined, seven of them (four FC and three ReHo
      measures) survived the SVM procedure of recursive feature elimination and
      together provided the highest group classification accuracy of 90.6%. The present
      findings extend previous studies of rfMRI in CD and offer insight into the
      underlying pathophysiology of the disorder in relation to network dysfunction and
      somatosensory disturbances. Hum Brain Mapp 38:4098-4108, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28504363
TI  - Allergic contact dermatitis caused by (meth)acrylates in nail cosmetic products
      in users and nail technicians - a 5-year study.
AB  - BACKGROUND: The increasing use of long-lasting nail aesthetic products has led to
      a growing number of cases of allergic contact dermatitis (ACD) caused by
      (meth)acrylates in recent years. OBJECTIVES: To provide information on ACD caused
      by (meth)acrylates related to nail cosmetic products. METHODS: We retrospectively
      reviewed files of patients with ACD caused by (meth)acrylates related to nail
      cosmetic products, who were patch tested between January 2011 and December 2015
      in 13 departments of dermatology in Portugal. RESULTS: Two-hundred and thirty
      cases of ACD caused by (meth)acrylates (55 technicians, 56 consumers, and 119
      with mixed exposure) had been documented, mostly as chronic hand eczema (93%).
      The most common sensitizers were: 2-hydroxyethyl methacrylate (HEMA), which was
      positive in 90% of the tested patients, 2-hydroxypropyl methacrylate (HPMA),
      which was positive in 64.1%, and ethyleneglycol dimethacrylate, which was
      positive in 54.5%. CONCLUSION: HEMA and HPMA were the most frequent positive
      allergens. HEMA, which identified 90% of cases, can be considered to be a good
      screening allergen. The high number of cases of ACD caused by (meth)acrylates in
      nail cosmetic products certainly warrants better preventive measures at the
      occupational level, and specific regulation in the field of consumer safety.

PMID- 28504364
TI  - Mindfulness meditation regulates anterior insula activity during empathy for
      social pain.
AB  - Mindfulness has been shown to reduce stress, promote health, and well-being, as
      well as to increase compassionate behavior toward others. It reduces distress to
      one's own painful experiences, going along with altered neural responses, by
      enhancing self-regulatory processes and decreasing emotional reactivity. In order
      to investigate if mindfulness similarly reduces distress and neural activations
      associated with empathy for others' socially painful experiences, which might in
      the following more strongly motivate prosocial behavior, the present study
      compared trait, and state effects of long-term mindfulness meditation (LTM)
      practice. To do so we acquired behavioral data and neural activity measures using
      functional magnetic resonance imaging (fMRI) during an empathy for social pain
      task while manipulating the meditation state between two groups of LTM
      practitioners that were matched with a control group. The results show increased
      activations of the anterior insula (AI) and anterior cingulate cortex (ACC) as
      well as the medial prefrontal cortex and temporal pole when sharing others'
      social suffering, both in LTM practitioners and controls. However, in LTM
      practitioners, who practiced mindfulness meditation just prior to observing
      others' social pain, left AI activation was lower and the strength of AI
      activation following the mindfulness meditation was negatively associated with
      trait compassion in LTM practitioners. The findings suggest that current
      mindfulness meditation could provide an adaptive mechanism in coping with
      distress due to the empathic sharing of others' suffering, thereby possibly
      enabling compassionate behavior. Hum Brain Mapp 38:4034-4046, 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28504365
TI  - Cost-effectiveness of non-surgical periodontal therapy for patients with type 2
      diabetes in the UK.
AB  - AIM: Periodontal therapy has been shown to reduce glycated haemoglobin in
      patients with diabetes, although considerable uncertainty remains regarding the
      sustainability of such changes. We evaluate the cost-effectiveness of non
      surgical periodontal therapy and rigorous maintenance treatment in patients with
      type 2 diabetes and periodontitis from a provider perspective in the UK. METHOD:
      Lifetime costs relating to periodontal treatment were modelled for a cohort of
      patients with type 2 diabetes. The projected lifetime impact of changes in
      glycated haemoglobin on diabetes treatment costs and quality adjusted life
      expectancy were estimated from a published simulation model. Costs and outcomes
      were combined to estimate the Incremental Cost-Effectiveness Ratio for
      periodontal therapy in patients with type 2 diabetes. RESULTS: The Incremental
      Cost-Effectiveness Ratio was L28,000 per Quality Adjusted Life-Year for a man
      aged 58 with glycated haemoglobin of 7%-7.9%. The results were particularly
      sensitive to assumptions on the impact of periodontal therapy on glycated
      haemoglobin, the proportion of patients who comply with maintenance therapy and
      the proportion of compliant patients who respond to treatment. CONCLUSION:
      Assuming improvements in glycated haemoglobin can be maintained, periodontal
      therapy may be cost-effective for patients with type 2 diabetes at acceptable
      cost-per-Quality Adjusted Life-Year thresholds in the UK.

PMID- 28504366
TI  - Mechanochemical Synthesis of Phosphazane-Based Frameworks.
AB  - Mechanochemistry is emerging as a powerful solvent-free approach to chemical
      synthesis, having been applied to metal oxides, pharmaceutical materials, organic
      compounds and to a lesser extent, coordination complex synthesis. Notably,
      examples of applications of mechanochemical methodologies in the synthesis of
      main-group compounds are few and far between. Herein, we demonstrate that ball
      milling enabled the solvent-free synthesis of a range of phosphazane frameworks
      with a broad substrate scope, yielding seven new acyclic and macrocyclic species.
      The strength of this methodology is highlighted by a fast, selective and high
      conversion product generation from poorly soluble starting materials, thereby
      demonstrating mechanochemistry as a real alternative to solution-based methods in
      synthetic main-group chemistry.

PMID- 28504368
TI  - Chemical Institute of Canada and Canadian Society for Chemistry Awards.

PMID- 28504367
TI  - Neuroprotective Natural Products for the Treatment of Parkinson's Disease by
      Targeting the Autophagy-Lysosome Pathway: A Systematic Review.
AB  - The autophagy-lysosome pathway (ALP) is a primary means by which damaged
      organelles and long-lived proteins are removed from cells and their components
      recycled. Impairment of the ALP has been found to be linked to the pathogenesis
      of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized
      by the accumulation of protein aggregates and loss of dopaminergic neurons in the
      midbrain. In recent years, some active compounds derived from plants have been
      found to regulate the ALP and to exert neuroprotective effects in experimental
      models of PD, raising the possibility that autophagy enhancement may be an
      effective therapeutic strategy in PD treatment. In this review, we summarize
      recent findings of natural products that enhance ALP and thereby protect against
      PD. Research articles were retrieved from PubMed using relevant keywords in
      combination. Papers related to the topic were identified, and then the
      reliability of the experiments was assessed in terms of methodology. The results
      suggest that targeting the ALP with natural products is a promising strategy for
      PD treatment. However, risk of bias exists in some studies due to the defective
      methodology. Rigorous experimental design following the guidelines of autophagy
      assays, molecular target identification and in vivo efficacy evaluation is
      critical for the development of ALP enhancers for PD treatment in future studies.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28504370
TI  - Topical photodynamic therapy: the preferred choice for cutaneous field
      cancerization?

PMID- 28504371
TI  - Image Gallery: Massive localized lymphoedema.

PMID- 28504373
TI  - Psoriasis and osteoporosis: the debate continues.

PMID- 28504374
TI  - Melanoma risk in congenital melanocytic naevi.

PMID- 28504375
TI  - Image Gallery: Generalized mucosal and cutaneous papillomatosis, a unique sign of
      malignant acanthosis nigricans.

PMID- 28504377
TI  - Interleukin-10-producing B-cells in autoimmune bullous diseases.

PMID- 28504379
TI  - T-type calcium channels as potential biomarkers in melanoma.

PMID- 28504381
TI  - Estimating the future health service burden of keratinocyte cancers in the U.K.

PMID- 28504382
TI  - Further evidence for carotenoid antioxidants in photoprotection.

PMID- 28504384
TI  - Image Gallery: Mucormycosis.

PMID- 28504386
TI  - Corrigendum.

PMID- 28504387
TI  - Corrigenda.

PMID- 28504385
TI  - Home phototherapy in the U.K.'s National Health Service: time to reach out.

PMID- 28504388
TI  - Challenges of treating melanoma in situ, lentigo maligna type: is pathological
      clearance the gold standard?

PMID- 28504389
TI  - Research questions for the treatment of alopecia areata have been prioritized.

PMID- 28504390
TI  - Identification of pharmacogenetic markers of treatment response to biologic
      therapies in psoriasis - is there a benefit?

PMID- 28504391
TI  - The impact of skin conditions on generic health-related quality of life.

PMID- 28504392
TI  - Molecular diagnosis of xeroderma pigmentosum variant in an isolated population:
      the interface between precision medicine and public health.

PMID- 28504393
TI  - Incorporating hair follicle cells in artificial skin.

PMID- 28504394
TI  - Image Gallery: Acute primary cutaneous nocardiosis due to Nocardia brasiliensis.

PMID- 28504395
TI  - Corrigendum.

PMID- 28504396
TI  - Psoriasis: inequality or individualized care?

PMID- 28504397
TI  - Hair-follicle dermal papilla and sheath fibroblasts provide a supportive
      microenvironment for human skin regeneration.

PMID- 28504398
TI  - Image Gallery: Palmoplantar hyperkeratosis in dermatomyositis with anti-PM/Scl
      antibodies.

PMID- 28504399
TI  - Aggression and its associations in patients with skin disease.

PMID- 28504401
TI  - Image Gallery: A case of pemphigus vulgaris following Simulium spp. (Diptera)
      bites.

PMID- 28504402
TI  - Epidermal growth factor receptor gaining impact in cutaneous squamous cell
      carcinoma.

PMID- 28504403
TI  - Long methylaminolaevulinate application does not increase clinical efficacy of
      photodynamic therapy in actinic keratosis, but leads to collateral damage.

PMID- 28504404
TI  - Prognostic factors in mycosis fungoides: international advances in the validation
      of prognostic indices.

PMID- 28504405
TI  - Image Gallery: Resolution of lichen striatus in a patient with coexisting chronic
      plaque psoriasis and vitiligo during secukinumab treatment.

PMID- 28504406
TI  - Corrigendum.

PMID- 28504407
TI  - Effects of space allocations and energy levels on growth performance and nutrient
      digestibility in growing and finishing pigs.
AB  - Two experiments were conducted to investigate effects of different space
      allocations and different dietary metabolizable energy (ME) levels on growth
      performance and nutrient digestibility in growing and finishing pigs. In
      experiment 1, a total of 84 growing pigs [(Yorkshire * Landrace) * Duroc] with an
      initial body weight (BW) of 27.10 +/- 1.60 kg were used in a 5-week trial. Pigs
      were blocked based on initial BW into a 2 * 2 factorial design with the following
      factors: (i) 0.60 or 0.80 m2 /pig space allocations; and (ii) 3,400 or 3,550
      kcal/kg ME of diets. In experiment 2, a total of 84 finishing pigs with an
      initial BW of 67.43 +/- 1.97 kg were used in a 10-week trial. Pigs were allotted
      based on initial BW into a 2 * 2 factorial design with the following factors: (i)
      0.81 or 1.08 m2 /pig space allocations; and (ii) 3,300 or 3,450 kcal/kg ME of
      diet. In experiment 1, high ME diet improved gain-to-feed ratio (G:F) in pigs
      with low space allocation but not in pigs in high space allocation (p < .05).
      Additionally, high ME diet increased apparent total tract digestibility (ATTD) of
      nitrogen in low space allocation but decreased ATTD of nitrogen in high space
      allocation (p < .05). In experiment 2, high ME diet improved average daily gain
      (ADG) and G:F in early-finishing pigs with low space allocation but not in pigs
      with high space allocation (p < .05). In conclusion, the provision of high ME
      diets was not enough to overcome the reduction in growth performance due to low
      space allocation but can improve feed efficiency in growing pigs and daily gain
      and feed efficiency early-finishing pigs.

PMID- 28504408
TI  - Kv1.3 channels facilitate the connection between metabolism and blood flow in the
      heart.
AB  - The connection between metabolism and flow in the heart, metabolic dilation, is
      essential for cardiac function. We recently found redox-sensitive Kv1.5 channels
      play a role in coronary metabolic dilation; however, more than one ion channel
      likely plays a role in this process as animals null for these channels still
      showed limited coronary metabolic dilation. Accordingly, we examined the role of
      another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary
      metabolic dilation. We measured myocardial blood flow (contrast echocardiography)
      during norepinephrine-induced increases in cardiac work (heart rate x mean
      arterial pressure) in WT, WT mice given correolide (preferential Kv1.3
      antagonist), and Kv1.3-null mice (Kv1.3-/- ). We also measured relaxation of
      isolated small arteries mounted in a myograph. During increased cardiac work,
      myocardial blood flow was attenuated in Kv1.3-/- and in correolide-treated mice.
      In isolated vessels from Kv1.3-/- mice, relaxation to H2 O2 was impaired (vs WT),
      but responses to adenosine and acetylcholine were equivalent to WT. Correolide
      reduced dilation to adenosine and acetylcholine in WT and Kv1.3-/- , but had no
      effect on H2 O2 -dependent dilation in vessels from Kv1.3-/- mice. We conclude
      that Kv1.3 channels participate in the connection between myocardial blood flow
      and cardiac metabolism.

PMID- 28504410
TI  - Unpacking the Ontogeny of Gesture Understanding: How Movement Becomes Meaningful
      Across Development.
AB  - Gestures, hand movements that accompany speech, affect children's learning,
      memory, and thinking (e.g., Goldin-Meadow, 2003). However, it remains unknown how
      children distinguish gestures from other kinds of actions. In this study, 4- to 9
      year-olds (n = 339) and adults (n = 50) described one of three scenes: (a) an
      actor moving objects, (b) an actor moving her hands in the presence of objects
      (but not touching them), or (c) an actor moving her hands in the absence of
      objects. Participants across all ages were equally able to identify actions on
      objects as goal directed, but the ability to identify empty-handed movements as
      representational actions (i.e., as gestures) increased with age and was
      influenced by the presence of objects, especially in older children.

PMID- 28504411
TI  - Directed C-H Activation and Tandem Cross-Coupling Reactions Using Palladium
      Nanocatalysts with Controlled Oxidation.
AB  - Controlled oxidation of palladium nanoparticles provided high-valent PdIV oxo
      clusters which efficiently promote directed C-H halogenation reactions. In
      addition, palladium nanoparticles can undergo changes in oxidation states to
      provide both high-valent PdIV and low-valent Pd0 species within one system, and
      thus a tandem reaction of C-H halogenation and cross-coupling (C-N, C-C, and C-S
      bond formation) was successfully established.

PMID- 28504412
TI  - Globalism versus Nationalism in Medical Physics.

PMID- 28504413
TI  - [60]Fullerene-Based Macrocycle Ligands.
AB  - Macrocycle ligands have three or more donor sites. Selective replacement of
      skeleton carbon atoms by heteroatoms and vacancies in C60 could lead to various
      macrocycle ligands with a cage-shaped backbone. Theoretical calculations indicate
      that such C60 -based macrocycle ligands are as stable as C60 thermodynamically
      according to their similar HOMO-LUMO gaps. The synthesis of these ligands is a
      challenging task. Nevertheless important progresses have been reported. This
      concept article focuses on the structures of possible C60 -based macrocycle
      ligands and related synthetic results.

PMID- 28504409
TI  - Multifunctional Liposomes for Image-Guided Intratumoral Chemo-Phototherapy.
AB  - Intratumoral (IT) drug injections reduce systemic toxicity, but delivered volumes
      and distribution can be inconsistent. To improve IT delivery paradigms, porphyrin
      phospholipid (PoP) liposomes are passively loaded with three hydrophilic cargos:
      sulforhodamine B, a fluorophore; gadolinium-gadopentetic acid, a magnetic
      resonance (MR) agent; and oxaliplatin, a colorectal cancer chemotherapeutic.
      Liposome composition is optimized so that cargo is retained in serum and storage,
      but is released in less than 1 min with exposure to near infrared light. Light
      triggered release occurs with PoP-induced photooxidation of unsaturated lipids
      and all cargos release concurrently. In subcutaneous murine colorectal tumors,
      drainage of released cargo is delayed when laser treatment occurs 24 h after IT
      injection, at doses orders of magnitude lower than systemic ones. Delayed light
      triggering results in substantial tumor shrinkage relative to controls a week
      following treatment, although regrowth occurs subsequently. MR imaging reveals
      that over this time frame, pools of liposomes within the tumor migrate to
      adjacent regions, possibly leading to altered spatial distribution during
      triggered drug release. Although further characterization of cargo loading and
      release is required, this proof-of-principle study suggests that multimodal
      theranostic IT delivery approaches hold potential to both guide injections and
      interpret outcomes, in particular when combined with chemo-phototherapy.

PMID- 28504414
TI  - High-Molecular-Weight Polynucleotides by Transferase-Catalyzed Living Chain
      Growth Polycondensation.
AB  - We present terminal deoxynucleotidyl transferase-catalyzed enzymatic
      polymerization (TcEP) for the template-free synthesis of high-molecular-weight,
      single-stranded DNA (ssDNA) and demonstrate that it proceeds by a living chain
      growth polycondensation mechanism. We show that the molecular weight of the
      reaction products is nearly monodisperse, and can be manipulated by the feed
      ratio of nucleotide (monomer) to oligonucleotide (initiator), as typically
      observed for living polymerization reactions. Understanding the synthesis
      mechanism and the reaction kinetics enables the rational, template-free synthesis
      of ssDNA that can be used for a range of biomedical and nanotechnology
      applications.

PMID- 28504415
TI  - Highly Luminescent Folate-Functionalized Au22 Nanoclusters for Bioimaging.
AB  - Gold nanoclusters are emerging as new materials for biomedical applications
      because of promises offered by their ultrasmall size and excellent
      biocompatibility. Here, the synthesis and optical and biological
      characterizations of a highly luminescent folate-functionalized Au22 cluster
      (Au22 -FA) are reported. The Au22 -FA clusters are synthesized by functionalizing
      the surface of Au22 (SG)18 clusters, where SG is glutathione, with benzyl
      chloroformate and folate. The functionalized clusters are highly water-soluble
      and exhibit remarkably bright luminescence with a quantum yield of 42%,
      significantly higher than any other water-soluble gold clusters protected with
      thiolate ligands. The folate groups conjugated to the gold cluster give rise to
      additional luminescence enhancement by energy transfer sensitization. The
      brightness of Au22 -FA is found to be 4.77 mM-1 cm-1 , nearly 8-fold brighter
      than that of Au22 (SG)18 . Further biological characterizations have revealed
      that the Au22 -FA clusters are well-suited for bioimaging. The Au22 -FA clusters
      exhibit excellent photostability and low toxicity; nearly 80% cell viability at
      1000 ppm of the cluster. Additionally, the Au22 -FA clusters show target
      specificity to folate-receptor positive cells. Finally, the time-course in vivo
      luminescence images of intravenous-injected mice show that the Au22 -FA clusters
      are renal-clearable, leaving only 8% of them remained in the body after 24 h post
      injection.

PMID- 28504416
TI  - Characterization and circulation of seasonal influenza viruses in Madrid, 2010
      2016.
AB  - Influenza virus infection is a major health care burden and is associated with
      significant morbidity and mortality. The 2009 influenza pandemic highlighted the
      importance of influenza surveillance. The objective of this study was to assess
      the epidemiology and activity of influenza A and B viruses in adults and children
      in the post-pandemic period with a special focus on the pediatric population. We
      performed a retrospective descriptive study involving adults and children with
      influenza-like illness at the Clinico San Carlos Hospital (Madrid, Spain) over
      six influenza seasons, between August 2010 and April 2016. Respiratory specimens
      were collected from 3131 patients and routinely processed for influenza
      diagnosis. Epidemiological analysis was performed in terms of gender, age, and
      seasonal distribution. Globally, Influenza A and B viruses were detected in the
      respiratory specimens of 696 (22.2%) of the 3131 studied population. Among all
      influenza positive specimens, 142 (20.4%) were influenza A(H1N1)pdm09, 61 (8.8%)
      were influenza A(H3N2), 321 (46.1%) were untypeable influenza A viruses and 166
      (23.9%) were influenza B. Co-infection by both influenza A and B viruses was
      detected in six patients (0.9%). Meanwhile, co-infection with other non-influenza
      respiratory viruses was identified in 5 children and 20 adults. Influenza
      A(H1N1)pdm09 virus activity has been significantly high since the 2009 pandemic
      and has gradually replaced the previously circulating seasonal influenza A(H1N1)
      virus. Moreover, influenza A(H3N2) virus activity remained at low levels during
      the last winter season while influenza B virus isolates increased significantly
      over the past 2 years.

PMID- 28504417
TI  - Laser-preparation of geometrically optimised samples for X-ray nano-CT.
AB  - A robust and versatile sample preparation technique for the fabrication of
      cylindrical pillars for imaging by X-ray nano-computed tomography (nano-CT) is
      presented. The procedure employs simple, cost-effective laser micro-machining
      coupled with focused-ion beam (FIB) milling, when required, to yield mechanically
      robust samples at the micrometre length-scale to match the field-of-view (FOV)
      for nano-CT imaging. A variety of energy and geological materials are exhibited
      as case studies, demonstrating the procedure can be applied to a variety of
      materials to provide geometrically optimised samples whose size and shape are
      tailored to the attenuation coefficients of the constituent phases. The procedure
      can be implemented for the bespoke preparation of pillars for both lab- and
      synchrotron-based X-ray nano-CT investigations of a wide range of samples.

PMID- 28504418
TI  - High-Flux Carbon Molecular Sieve Membranes for Gas Separation.
AB  - Carbon membranes have great potential for highly selective and cost-efficient gas
      separation. Carbon is chemically stable and it is relative cheap. The controlled
      carbonization of a polymer coating on a porous ceramic support provides a 3D
      carbon material with molecular sieving permeation performance. The carbonization
      of the polymer blend gives turbostratic carbon domains of randomly stacked
      together sp2 hybridized carbon sheets as well as sp3 hybridized amorphous carbon.
      In the evaluation of the carbon molecular sieve membrane, hydrogen could be
      separated from propane with a selectivity of 10 000 with a hydrogen permeance of
      5 m3 (STP)/(m2 hbar). Furthermore, by a post-synthesis oxidative treatment, the
      permeation fluxes are increased by widening the pores, and the molecular sieve
      carbon membrane is transformed from a molecular sieve carbon into a selective
      surface flow carbon membrane with adsorption controlled performance and becomes
      selective for carbon dioxide.

PMID- 28504419
TI  - Congenital nephrogenic diabetes insipidus complicated with Hinman syndrome.

PMID- 28504420
TI  - Use of Supramolecular Assemblies as Lithographic Resists.
AB  - A new resist material for electron beam lithography has been created that is
      based on a supramolecular assembly. Initial studies revealed that with this
      supramolecular approach, high-resolution structures can be written that show
      unprecedented selectivity when exposed to etching conditions involving plasmas.

PMID- 28504421
TI  - Bioinformatics Analysis on Molecular Mechanism of Green Tea Compound
      Epigallocatechin-3-Gallate Against Ovarian Cancer.
AB  - Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active
      catechin in green tea, and it exerts multiple effects in humans through
      mechanisms that remain to be clarified. The present study used bioinformatics to
      identify possible mechanisms by which EGCG reduces the risk of ovarian cancer.
      Possible human protein targets of EGCG were identified in the PubChem database,
      possible human gene targets were identified in the National Center for
      Biotechnology Information database, and then both sets of targets were analyzed
      using Ingenuity Pathway Analysis (IPA). The results suggest that signaling
      proteins affected by EGCG in ovarian cancer, which include JUN, FADD, NFKB1, Bcl
      2, HIF1alpha, and MMP, are involved primarily in cell cycle, cellular assembly
      and organization, DNA replication, etc. These results identify several specific
      proteins and pathways that may be affected by EGCG in ovarian cancer, and they
      illustrate the power of integrative informatics and chemical fragment analysis
      for focusing mechanistic studies.

PMID- 28504422
TI  - Effects of Mobile Phones on Children's and Adolescents' Health: A Commentary.
AB  - The use of digital technology has grown rapidly during the last couple of
      decades. During use, mobile phones and cordless phones emit radiofrequency (RF)
      radiation. No previous generation has been exposed during childhood and
      adolescence to this kind of radiation. The brain is the main target organ for RF
      emissions from the handheld wireless phone. An evaluation of the scientific
      evidence on the brain tumor risk was made in May 2011 by the International Agency
      for Research on Cancer at World Health Organization. The scientific panel reached
      the conclusion that RF radiation from devices that emit nonionizing RF radiation
      in the frequency range 30 kHz-300 GHz is a Group 2B, that is, a "possible" human
      carcinogen. With respect to health implications of digital (wireless)
      technologies, it is of importance that neurological diseases, physiological
      addiction, cognition, sleep, and behavioral problems are considered in addition
      to cancer. Well-being needs to be carefully evaluated as an effect of changed
      behavior in children and adolescents through their interactions with modern
      digital technologies.

PMID- 28504424
TI  - The current state of postoperative imaging in the presence of deep brain
      stimulation electrodes.

PMID- 28504423
TI  - Genetic vulnerabilities to prenatal alcohol exposure: Limb defects in sonic
      hedgehog and GLI2 heterozygous mice.
AB  - BACKGROUND: Genetic factors influence the physical and neurobehavioral
      manifestations of prenatal alcohol exposure (PAE). Animal models allow the
      investigation of specific genes that confer vulnerability to, or protection from,
      birth defects associated with fetal alcohol spectrum disorders (FASDs). The
      objective of the present experiments was to determine if genetic alterations in
      the Sonic Hedgehog (Shh) signaling pathways affect the vulnerability to PAE
      induced skeletal defects involving the forelimbs and/or hindlimbs. METHOD: Wild
      type C57BL/6J female mice were bred with males in which one copy of the Shh or
      Gli2 genes had been knocked out, to produce litters with both wild-type (+/+) and
      heterozygous (+/-) embryos. Alcohol doses (two injections of 2.9 g/kg, 4 hours
      apart) or vehicles were administered starting at gestational day (GD) 9.25, 9.5,
      or 9.75, a critical exposure time for inducing limb defects. Limb defects were
      examined at GD 17 using a dysmorphology scale based on abnormalities ranging from
      increased interdigital spacing to the deletion of multiple fingers and the ulna.
      RESULTS: Alcohol treatment caused a high incidence of forelimb defects,
      particularly on the right side, that was higher in Shh+/- and Gli2+/- fetuses
      compared to wild-type fetuses. Dysmorphology scores were also significantly
      higher in the Shh+/- and Gli2+/- mice. CONCLUSIONS: These results extend previous
      findings demonstrating enhanced sensitivity to PAE-induced craniofacial
      dysmorphology and support the hypothesis that genetic alterations in the Shh
      signaling pathway influences the vulnerability to alcohol-induced birth defects.
      Moreover, these results emphasize the importance of understanding the
      interactions between genes and prenatal exposure to alcohol or other teratogens.
      Birth Defects Research 109:860-865, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28504425
TI  - Active surveillance to update county scale distribution of four tick species of
      medical and veterinary importance in Oklahoma.
AB  - The incidence of tick-borne disease continues to increase in humans and companion
      animals in the United States, yet distribution maps for several tick vectors in
      Oklahoma, including Dermacentor variabilis, Dermacentor albipictus, Ixodes
      scapularis, and Amblyomma maculatum, are not available or are outdated. To
      address this issue, county-scale tick records from peer-reviewed literature and
      passive collections were reviewed for Oklahoma. Additionally, dry ice traps, tick
      drags, and harvested deer were utilized to actively collect adult ticks
      throughout the state. Through these methods, D. variabilis, D. albipictus, I.
      scapularis, and A. maculatum were identified in 88% (68/77), 45.4% (35/77), 66.2%
      (51/77), and 64.9% (50/77) of the counties in Oklahoma, respectively. Baseline
      maps were developed for the distribution of D. variabilis and D. albipictus and
      distribution maps were updated for I. scapularis and A. maculatum. This data
      confirms that these four species of ticks continue to be widespread within
      Oklahoma with a western expansion of the range of I. scapularis within the state.
      These results assist efforts to better understand the epidemiology of the
      different diseases caused by pathogens transmitted by these tick species within
      the Great Plains region.

PMID- 28504426
TI  - Mosquito distribution in a saltmarsh: determinants of eggs in a variable
      environment.
AB  - Two saltmarsh mosquitoes dominate the transmission of Ross River virus (RRV,
      Togoviridae: Alphavirus), one of Australia's most prominent mosquito-borne
      diseases. Ecologically, saltmarshes vary in their structure, including habitat
      types, hydrological regimes, and diversity of aquatic fauna, all of which drive
      mosquito oviposition behavior. Understanding the distribution of vector
      mosquitoes within saltmarshes can inform early warning systems, surveillance, and
      management of vector populations. The aim of this study was to identify the
      distribution of Ae. camptorhynchus, a known vector for RRV, across a saltmarsh
      and investigate the influence that other invertebrate assemblage might have on
      Ae. camptorhynchus egg dispersal. We demonstrate that vegetation is a strong
      indicator for Ae. camptorhynchus egg distribution, and this was not correlated
      with elevation or other invertebrates located at this saltmarsh. Also, habitats
      within this marsh are less frequently inundated, resulting in dryer conditions.
      We conclude that this information can be applied in vector surveillance and
      monitoring of temperate saltmarsh environments and also provides a baseline for
      future investigations into understanding mosquito vector habitat requirements.

PMID- 28504428
TI  - The effect of inbreeding and larval feeding regime on immature development of
      Aedes albopictus.
AB  - The fundamental approach to the biological control of Aedes albopictus requires
      the mass rearing of mosquitoes and the release of highly competitive adults in
      the field. As the fitness of adults is highly dependent on the development of
      immatures, we aimed to identify the minimum feeding regime required to produce
      viable and competitive adults by evaluating three response parameters:
      development duration, immature mortality, and adult wing length. Our study
      suggests at least 0.60 mg/larva/day of larval diet composed of dog food, dried
      beef liver, yeast, and milk powder in a weight ratio of 2:1:1:1 is required to
      maximize adult fitness. With standardized protocols in mass rearing, intensive
      studies can be readily conducted on mosquito colonies to facilitate comparisons
      across laboratories. This study also evaluated the differences in response of
      laboratory and field strains under different feeding regimes. We found that
      strain alone did not exert substantial effects on all response parameters.
      However, the field strain exhibited significantly lower immature mortality than
      the laboratory strain under the minimum feeding regime. Females and males of the
      laboratory strain had longer wing lengths under nutritional constraint due to the
      higher mortality that resulted in reduced interactions with the remaining larvae.
      Meanwhile, the field strain exhibited heterogeneous duration of immature
      development compared with the laboratory strain. The disparities demonstrated by
      the two strains in this study suggest the effect of inbreeding surfaced after a
      long term of laboratory colonization. Despite the trade-offs resulting from
      laboratory colonization, the competitiveness of the laboratory strain of Ae.
      albopictus is comparable to the field strain, provided the larvae are fed
      optimally.

PMID- 28504429
TI  - Species composition and temporal distribution of adult ixodid ticks and
      prevalence of Borrelia burgdorferi sensu lato and Rickettsia species in Orange
      County, California.

PMID- 28504430
TI  - Variation of tsetse fly abundance in relation to habitat and host presence in the
      Maasai Steppe, Tanzania.
AB  - Human activities modify ecosystem structure and function and can also alter the
      vital rates of vectors and thus the risk of infection with vector-borne diseases.
      In the Maasai Steppe ecosystem of northern Tanzania, local communities depend on
      livestock and suitable pasture that is shared with wildlife, which can increase
      tsetse abundance and the risk of trypanosomiasis. We monitored the monthly tsetse
      fly abundance adjacent to Tarangire National Park in 2014-2015 using geo
      referenced, baited epsilon traps. We examined the effect of habitat types and
      vegetation greenness (NDVI) on the relative abundance of tsetse fly species. Host
      availability (livestock and wildlife) was also recorded within 100*100 m of each
      trap site. The highest tsetse abundance was found in the ecotone between Acacia
      Commiphora woodland and grassland, and the lowest in riverine woodland. Glossina
      swynnertoni was the most abundant species (68%) trapped throughout the entire
      study, while G. pallidipes was the least common (4%). Relative species abundance
      was negatively associated with NDVI, with greatest abundance observed in the dry
      season. The relationship with the abundance of wildlife and livestock was more
      complex, as we found positive and negative associations depending on the host and
      fly species. While habitat is important for tsetse distribution, hosts also play
      a critical role in affecting fly abundance and, potentially, trypanosomiasis
      risk.

PMID- 28504431
TI  - The mosquito fauna of the western region of Spain with emphasis on ecological
      factors and the characterization of Culex pipiens forms.
AB  - : This study updates the diversity, distribution, and seasonal trends of
      mosquitoes in a western region of Spain, assesses ecological determinants of
      Culex pipiens s.l., and determines form composition of Cx. pipiens s.s.
      POPULATIONS: A total of 1,495 mosquitoes of 16 species was collected during 2012
      2013, of which Cx. pipiens s.l. and Cx. theileri were the most abundant. Five new
      records for An. maculipennis s.s., Orthopodomyia pulcripalpis, Aedes
      (Ochlerotatus) punctor, Cx. europaeus, and Cx. modestus were found for this
      region. Cx. pipiens density varied across weather and habitat patterns,
      correlating positively with high temperatures and with a preference for urbanized
      areas and rural areas within a proximity of ovine farms. Moreover, molecular
      identification by CQ11FL was performed in 467 Cx. pipiens s.s., detecting both
      pipiens (66%) and molestus (8.4%) forms coexisting in different habitats (urban,
      peri-urban and rural) aboveground with a high degree of hybridization (25.7%).
      The abundance of Cx. pipiens in urban areas and farms, with the presence of
      hybrids, may increase their capacity to act as bridge vectors for the
      transmission of arboviral infections. These data will be helpful for further
      implementation of entomological programs focused on risk assessment for
      arboviruses or other mosquito-borne pathogens.

PMID- 28504432
TI  - Control of male Aedes albopictus Skuse (Diptera: Culicidae) using boric acid
      sugar bait and its impact on female fecundity and fertility.

PMID- 28504433
TI  - Influence of shading and pedestrian traffic on the preference of Aedes
      (Stegomyia) aegypti (Diptera: Culicidae) for oviposition microenvironments.
AB  - Aedes aegypti mosquitoes are highly adaptable to abiotic stimuli. To evaluate the
      influence of shading and pedestrian traffic on the preference of Ae. aegypti for
      oviposition microenvironments, 20 sites were sampled weekly using ovitraps within
      the perimeter of Universidade Federal do Espirito Santo, located in Sao Mateus,
      Espirito Santo, Brazil. A spatial and statistical analysis was performed in order
      to assess the relationship between shading time, pedestrian traffic, and the
      presence of biological forms of Ae. aegypti. A temporal analysis of temperature
      and precipitation influence on oviposition was also made. Between June, 2013 and
      June, 2014, 7,362 Ae. aegypti eggs were collected. Over a 12-month period, we
      made weekly collections of Ae. aegypti eggs from ovitraps. Pedestrian traffic and
      shading time influenced the number of positive ovitraps; precipitation and
      temperature were correlated with the number of positive ovitraps (p <0.05). We
      conclude that the influence of temperature and precipitation was not significant
      for the oviposition index, and the frequency of oviposition was directly
      proportional to the number of individuals moving close to the traps during
      periods of greater shading.

PMID- 28504435
TI  - An updated checklist of the Culicidae (Diptera) of Morocco, with notes on species
      of historical and current medical importance.
AB  - An updated checklist of the mosquito species (Diptera: Culicidae) recorded in
      Morocco from 1916 to 2016 is provided, including synonyms and synonymous usage
      for each species. Forty-three species belonging to seven genera are recorded so
      far: Anopheles (9), Aedes (12) Coquillettidia (2), Culex (12), Culiseta (5),
      Orthopodomyia (1) and Uranotaenia (2). Traditional and equivalent names in the
      polyphyletic concept of Aedes are provided for the aedine species. The historical
      importance and current potential threat of mosquitoes to human health in Morocco
      is reviewed.

PMID- 28504436
TI  - Mosquito species distribution across urban, suburban, and semi-rural residences
      in San Antonio, Texas.

PMID- 28504437
TI  - Seasonal variation of tsetse fly species abundance and prevalence of trypanosomes
      in the Maasai Steppe, Tanzania.
AB  - Tsetse flies, the vectors of trypanosomiasis, represent a threat to public health
      and economy in sub-Saharan Africa. Despite these concerns, information on
      temporal and spatial dynamics of tsetse and trypanosomes remain limited and may
      be a reason that control strategies are less effective. The current study
      assessed the temporal variation of the relative abundance of tsetse fly species
      and trypanosome prevalence in relation to climate in the Maasai Steppe of
      Tanzania in 2014-2015. Tsetse flies were captured using odor-baited Epsilon traps
      deployed in ten sites selected through random subsampling of the major vegetation
      types in the area. Fly species were identified morphologically and trypanosome
      species classified using PCR. The climate dataset was acquired from the African
      Flood and Drought Monitor repository. Three species of tsetse flies were
      identified: G. swynnertoni (70.8%), G. m. morsitans (23.4%), and G.pallidipes
      (5.8%). All species showed monthly changes in abundance with most of the flies
      collected in July. The relative abundance of G. m. morsitans and G. swynnertoni
      was negatively correlated with maximum and minimum temperature, respectively.
      Three trypanosome species were recorded: T. vivax (82.1%), T. brucei (8.93%), and
      T. congolense (3.57%). The peak of trypanosome infections in the flies was found
      in October and was three months after the tsetse abundance peak; prevalence was
      negatively correlated with tsetse abundance. A strong positive relationship was
      found between trypanosome prevalence and temperature. In conclusion, we find that
      trypanosome prevalence is dependent on fly availability, and temperature drives
      both tsetse fly relative abundance and trypanosome prevalence.

PMID- 28504438
TI  - Aedes aegypti (L.) mosquitoes in Trinidad, West Indies: longevity case studies.
AB  - Few laboratory and field studies have reported long survival periods for Ae.
      aegypti females and even fewer have designed experiments to characterize this
      important life history trait. This study was conducted under laboratory
      conditions to determine the number of blood meals taken by individual females,
      the number of eggs laid per individual female, the length of the gonotrophic
      cycle, and the duration of female survival. The results showed individual females
      oviposited between 670 and 1,500 eggs throughout their lifetimes, females
      undergoing large numbers of gonotrophic cycles and surviving up to 224 days.
      These results are discussed in the context of vector competence, unique
      alternating high and low oviposition patterns observed after week 14, and
      resource partitioning/allocation by older Ae. aegypti females after blood
      feeding.

PMID- 28504440
TI  - Corrigendum to: DNA-based identification and OspC serotyping in cultures of
      Borrelia burgdorferi s.l. isolated from ticks collected in the Moravia (Czech
      Republic).

PMID- 28504439
TI  - Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi sensu lato, and
      Toxoplasma gondii in Ixodes ricinus (Acari, Ixodida) ticks collected from
      Slowinski National Park (Northern Poland).

PMID- 28504442
TI  - Involvement of invasive eastern red cedar (Juniperus virginiana) in the expansion
      of Amblyomma americanum in Oklahoma.

PMID- 28504441
TI  - Vector bionomics and malaria transmission along the Thailand-Myanmar border: a
      baseline entomological survey.
AB  - Baseline entomological surveys were conducted in four sentinel sites along the
      Thailand-Myanmar border to address vector bionomics and malaria transmission in
      the context of a study on malaria elimination. Adult Anopheles mosquitoes were
      collected using human-landing catch and cow-bait collection in four villages
      during the rainy season from May-June, 2013. Mosquitoes were identified to
      species level by morphological characters and by AS-PCR. Sporozoite indexes were
      determined on head/thoraces of primary and secondary malaria vectors using real
      time PCR. A total of 4,301 anopheles belonging to 12 anopheline taxa were
      identified. Anopheles minimus represented >98% of the Minimus Complex members
      (n=1,683), whereas the An. maculatus group was composed of two dominant species,
      An. sawadwongporni and An. maculatus. Overall, 25 Plasmodium-positive mosquitoes
      (of 2,323) were found, representing a sporozoite index of 1.1% [95%CI 0.66-1.50].
      The transmission intensity as measured by the EIR strongly varied according to
      the village (ANOVA, F=17.67, df=3, P<0.0001). Our findings highlight the
      diversity and complexity of the biting pattern of malaria vectors along the
      Thailand-Myanmar border that represent a formidable challenge for malaria control
      and elimination.

PMID- 28504443
TI  - Bat ectoparasites (Nycteribiidae, Streblidae, Siphonaptera, Heteroptera,
      Mesostigmata, Argasidae, and Ixodidae) from Algeria.
AB  - Twenty two species of ectoparasites (Family Nycteribiidae: Nycteribia
      (Listropoda) schmidlii schmidlii, Nycteribia (Nycteribia) latreillii, Nycteribia
      (Nycteribia) pedicularia, Penicillidia (Penicillidia) dufourii, and Phthiridium
      biarticulatum; Family Streblidae: Brachytarsina (Brachytarsina) flavipennis and
      Raymondia huberi; Order Siphonaptera: Rhinolophopsylla unipectinata arabs,
      Nycteridopsylla longiceps, Araeopsylla gestroi, Ischnopsyllus intermedius, and
      Ischnopsyllus octactenus; Order Heteroptera: Cimex pipistrelli, Cimex
      lectularius, and Cacodmus vicinus; Class Arachnida: Order Mesostigmata:
      Spinturnix myoti and Eyndhovenia euryalis; Order Ixodida: Family Argasidae: Argas
      transgariepinus and Argas vespertilionis; Family Ixodidae: Hyalomma dromedarii,
      Ixodes ricinus, and Ixodes vespertilionis) were recovered from 19 bat species in
      Algeria. New host records for bats are recorded for the first time: N. schmidlii
      from Rh. clivosus and R. cystops; N. latreillii from Rh. blasii and P. gaisleri;
      R. huberi from Rh. clivosus; C. pipistrelli from E. isabellinus and H. savii; C.
      vicinus from E. isabellinus; S. myoti from P. gaisleri; E. euryalis from P.
      gaisleri and Rh. blasii; A. vespertilionis from P. gaisleri; I. ricinus from T.
      teniotis and Rh. hipposideros and H. dromedarii from P. kuhlii. Raymondia huberi
      is recorded for the first time from Algeria.

PMID- 28504444
TI  - Diversity, ecology, and seasonality of sand flies (Diptera: Psychodidae) of the
      Jenin District (Palestinian Territories).
AB  - The diversity, ecology, and seasonality for sand flies from two localities in
      Jenin District, the Palestinian Territories, were studied. A total of 12,579 sand
      flies (5,420 Phlebotomus and 7,159 Sergentomyia) were collected during the study
      period. The genera Phlebotomus and Sergentomyia are represented by 13 and nine
      species and subspecies, respectively. Species account was given for all collected
      species. CDC light traps yielded 7,649 (60.8%) of the total captured sand flies,
      while sticky traps and aspirators contributed to 36.4 and 2.8% of the total
      collected specimens, respectively. Phlebotomus sergenti and P. syriacus showed
      two peaks, one in July and one in October. Phlebotomus tobbi showed one peak
      towards the end of the summer in September and August, while P. papatasi showed a
      bimodal peaks pattern, one in June and one in October. Phlebotomus canaaniticus
      showed a peak in August. P. perfiliewi transcaucasicus and P. neglectus showed a
      peak in October. Sergentomyia dentata showed one peak in August and increasing
      numbers from June to August, declining afterwards. Other species, such as S.
      theodori, had one peak in June, S. taizi had steady numbers across the summer,
      and S. christophersi had a peak in August.

PMID- 28504445
TI  - First record of Anopheles daciae (Linton, Nicolescu & Harbach, 2004) in Poland.

PMID- 28504446
TI  - Effects of a larval mosquito biopesticide and Culex larvae on a freshwater
      nanophytoplankton (Selenastrum capricornatum) under axenic conditions.
AB  - The effects of microbial biopesticides used for mosquito control on autotrophic
      microorganisms such as nanophytoplankton are equivocal. We examined impacts of
      mosquito biopesticides and mosquito larvae on primary producers in two
      independent experiments. In the first experiment, we examined the effects of a
      commonly used microbial biopesticide formulation (VectoMax(r) CG) on a
      unicellular microalga, Selenastrum capricornatum Printz, under axenic laboratory
      conditions. The biopesticide treatments included two concentrations (0.008 and
      0.016 g liter-1 ) of VectoMax(r) CG and two controls (one untreated and another
      with autoclaved 0.016 g VectoMax(r) CG liter-1 ) in replicated axenic
      experimental microcosms. Spectrophotometric analysis of chlorophyll a (proxy for
      algal biomass) and direct enumeration of algal cells following the treatments
      revealed no significant effects of the microbial biopesticide on algal population
      growth during the four-week study. In the second experiment, we tested the
      effects of different densities of Culex larvae on the population of S.
      capricornatum. Effects of mosquito larvae feeding on S. capricornatum were
      significant with a curvilinear relationship between larval density and algal
      abundance in the water column. Together, these studies demonstrated a lack of
      direct cytological/toxicological effects of Bacillus-based microbial pesticides
      on freshwater primary production and support the hypothesis that the reduction in
      algal primary production previously reported when Bti products were applied to
      aquatic environments was likely independent of the Bacillus-based larvicidal
      toxins. Instead, it was likely mediated by microbial interactions in the water
      column and the trophic cascade effects that resulted from the removal of larval
      mosquitoes. These studies suggest that mosquito larvae independent of pesticide
      application can influence primary production. Our method of evaluating
      biopesticides against small photoautotrophs can be very useful for studying the
      unintended effects on autotrophic microorganisms of other pesticides, including
      herbicides and pesticides applied to aquatic environments.

PMID- 28504447
TI  - Tick infestation of small mammals in an English woodland.
AB  - Tick infestations on small mammals were studied from April to November, 2010, in
      deciduous woodland in southern England in order to determine whether co
      infestations with tick stages occurred on small mammals, a key requirement for
      endemic transmission of tick-borne encephalitis virus (TBEV). A total of 217
      small mammals was trapped over 1,760 trap nights. Yellow-necked mice (Apodemus
      flavicollis) made up the majority (52.5%) of animals, followed by wood mice (A.
      sylvaticus) 35.5% and bank voles (Myodes glareolus) 12%. A total of 970 ticks was
      collected from 169 infested animals; 96% of ticks were Ixodes ricinus and 3% I.
      trianguliceps. Over 98% of ticks were larval stages. Mean infestation intensities
      of I. ricinus were significantly higher on A. flavicollis (6.53 +/- 0.67) than on
      A. sylvaticus (4.96 +/- 0.92) and M. glareolus (3.25 +/- 0.53). Infestations with
      I. ricinus were significantly higher in August than in any other month. Co
      infestations with I. ricinus nymphs and larvae were observed on six (3.6%)
      infested individuals, and fifteen small mammals (8.9%) supported I. ricinus - I.
      trianguliceps co-infestations. This work contributes further to our understanding
      of European small mammal hosts that maintain tick populations and their
      associated pathogens, and indicates that co-infestation of larvae and nymph ticks
      does occur in lowland UK. The possible implications for transmission of tick
      borne encephalitis virus between UK ticks and small mammals are discussed.

PMID- 28504448
TI  - Efficacy of a fipronil bait in reducing the number of fleas (Oropsylla spp.)
      infesting wild black-tailed prairie dogs.
AB  - Bubonic plague (Yersinia pestis) is a deadly zoonosis with black-tailed prairie
      dogs (Cynomys ludovicianus) as a reservoir host in the United States. Systemic
      insecticides are a promising means of controlling the vectors, Oropsylla spp.
      fleas, infesting these prairie dogs, subsequently disrupting the Y. pestis cycle.
      The objective of this study was to conduct a field trial evaluating the efficacy
      of a grain rodent bait containing fipronil (0.005%) against fleas infesting
      prairie dogs. The study was performed in Larimer County, CO, where bait was
      applied to a treatment area containing a dense prairie dog population, three
      times over a three-week period. Prairie dogs were captured and combed for fleas
      during four study periods (pre-, mid-, 1st post-, and 2nd post-treatment).
      Results indicated the use of bait containing fipronil significantly reduced flea
      burden. The bait containing fipronil was determined to reduce the mean number of
      fleas per prairie dog >95% for a minimum of 52 days post-initial treatment
      application and 31 days post-final treatment application. These results suggest
      the potential for this form of treatment to reduce flea population density on
      prairie dogs, and subsequently plague transmission, among mammalian hosts across
      the United States and beyond.

PMID- 28504449
TI  - A decade of colonization: the spread of the Asian tiger mosquito in Pennsylvania
      and implications for disease risk.
AB  - In recent decades, the Asian tiger mosquito expanded its geographic range
      throughout the northeastern United States, including Pennsylvania. The
      establishment of Aedes albopictus in novel areas raises significant public health
      concerns, since this species is a highly competent vector of several arboviruses,
      including chikungunya, West Nile, and dengue. In this study, we used geographic
      information systems (GIS) to examine a decade of colonization by Ae. albopictus
      throughout Pennsylvania between 2001 and 2010. We examined the spatial and
      temporal distribution of Ae. albopictus using spatial statistical analysis and
      examined the risk of dengue virus transmission using a model that captures the
      probability of transmission. Our findings show that since 2001, the Ae.
      albopictus population in Pennsylvania has increased, becoming established and
      expanding in range throughout much of the state. Since 2010, imported cases of
      dengue fever have been recorded in Pennsylvania. Imported cases of dengue, in
      combination with summer temperatures conducive for virus transmission, raise the
      risk of local disease transmission.

PMID- 28504450
TI  - The influence of environmental management and animal shelters in vector control
      of Culicoides (Diptera, Ceratopogonidae) in northeastern Brazil.
AB  - We investigated whether biting midges in peridomestic environments are affected
      by environmental management practices and the presence of domestic animals. We
      used CDC light traps to collect midges in 112 residences across 24 locations
      along tourism routes of Maranhao, Brazil. The collection areas were characterized
      as follows: i) peridomestic area with domestic animals and without management
      (dirty); ii) peridomestic with domestic animals and management (clean); iii)
      peridomestic without animals and with management (clean); iv) peridomestic
      without animals and without management (dirty). The first two treatments had
      higher biting midge species richness and abundance, respectively. Generalized
      linear models indicated a positive correlation between the presence of domestic
      animals and midge abundance, with an approximate four-fold increase in Culicoides
      (Diptera: Ceratopogonidae) abundance in peridomestic areas with animals. The same
      model showed that domestic animals have no influence on richness. Environmental
      management does not appear to influence species richness or abundance of biting
      midges.

PMID- 28504451
TI  - Biological parameters of interbreeding populations of Meccus phyllosomus
      longipennis (Usinger), 1939 (Hemiptera: Reduviidae: Triatominae) in Mexico.

PMID- 28504452
TI  - Effect of CO2 concentration on mosquito collection rate using odor-baited suction
      traps.
AB  - Carbon dioxide (CO2 ) has been used for decades to enhance capture of host
      seeking mosquitoes when released in association with traps commonly used by
      mosquito and vector control agencies. However, there is little published work
      evaluating the effect of altering CO2 release rates relative to the number of
      mosquitoes captured in these traps. This study investigated how varying CO2
      concentration altered the mosquito collection rate at a freshwater wetlands in
      southern California. Host-seeking mosquitoes were captured in CDC-style traps
      baited with one of six CO2 release rates ranging from 0-1,495 ml/min from gas
      cylinders. Species captured were Aedes vexans, Anopheles franciscanus, An.
      hermsi, Culex erythrothorax, and Cx. tarsalis. A biting midge, Culicoides
      sonorensis, was also captured. For all species, increasing CO2 release rates
      resulted in increasing numbers of individual females captured, with the relative
      magnitude of this increase associated to some extent with known feeding
      preferences of these species. We found that variation in CO2 release rate can
      significantly alter mosquito capture rates, potentially leading to imprecise
      estimates of vector activity if the relationship of CO2 release rate to mosquito
      capture rate is not considered.

PMID- 28504453
TI  - Reduced productivity of Culex pipiens and Cx. restuans (Diptera: Culicidae)
      mosquitoes in parking area catch basins in the northeast Chicago metropolitan
      area.
AB  - From June to September, 2016, 100 catch basins in eight parking areas were
      monitored weekly for the presence of mosquito pupae in the operational area of
      the North Shore Mosquito Abatement District (NSMAD) located just north of
      Chicago, IL, U.S.A. Weekly results from these basins were compared to weekly
      samples taken from residential street catch basins, the most common type of catch
      basin treated seasonally by the NSMAD with larvicides. Over the 17 study weeks,
      residential street basins had a mean rate of productivity (pupae per basin-visit)
      12 times that of parking area catch basins. The two parking area sites with the
      highest mean rate of productivity were associated with county forest preserves.
      Productivity in both street and parking area basins was positively associated
      with the presence of three or more deciduous trees within 20 m of basins and if
      they were located directly adjacent to curbs. Alternatively, productivity was
      negatively associated with the proportion of impervious surface within 10 m of
      basins and weekly rainfall. Findings suggest that reduced catch basin larvicide
      applications may be appropriate in many parking area sites.

PMID- 28504454
TI  - Ruthenium Complexes with Strongly Electron-Donating Terpyridine Ligands: Effect
      of the Working Electrode on Electrochemical and Spectroelectrochemical
      Properties.
AB  - The combination of 2,2':6',2''-terpyridines (tpy) and RuII is known to deliver
      molecular and supramolecular assemblies with remarkable properties. Here new RuII
      complexes, with modified tpy ligands substituted with varying numbers of
      dimethlyamino groups, are presented. Electrochemistry shows that the
      incorporation of the strongly electron-donating groups on the tpy ligands leads
      to a negative shift of the RuII oxidation potential by close to 1 V. The
      reductive electrochemical responses are strongly dependent on the nature of the
      working electrode, with glassy carbon and gold working electrodes showing the
      best results. These observations led to the development of a modified Optically
      Transparent Thin Layer Electrochemical (OTTLE) cell, based on a gold working
      electrode. The use of UV/Vis/NIR spectroelectrochemical methods with that OTTLE
      cell, together with simulations of the cyclic voltammograms, allowed the
      characterization of four reduction steps in these complexes, the final two of
      which lead to bond activations at the ruthenium center. This observation is to
      the best of our knowledge unprecedented in coordinatively saturated complexes of
      type [Ru(tpy)2 ]2+ . The various redox states of the complexes were characterized
      by EPR spectroelectrochemistry and through DFT calculations. The results
      presented here establish these substituted tpy ligands as highly attractive
      ligands in coordination chemistry, and display the utility of a gold-based OTTLE
      cell for spectroelectrochemical measurements.

PMID- 28504455
TI  - Mycoplasma bovis isolates from dairy calves in Japan have less susceptibility
      than a reference strain to all approved macrolides associated with a point
      mutation (G748A) combined with multiple species-specific nucleotide alterations
      in 23S rRNA.
AB  - Erythromycin, tylosin and tilmicosin are approved for use in cattle in Japan, the
      latter two being used to treat Mycoplasma bovis infection. In this study, 58 M.
      bovis isolates obtained from Japanese dairy calves all exhibited reduced
      susceptibility to these macrolides, this widespread reduced susceptibility being
      attributable to a few dominant lineages. All 58 isolates contained the G748A
      variant in both the rrl3 and rrl4 alleles of 23S rRNA, whereas a reference strain
      (PG45) did not. G748 localizes in the central loop of domain II (from C744 to
      A753) of 23S rRNA, which participates in binding to mycinose, a sugar residue
      present in both tylosin and tilmicosin. A number of in vitro-selected mutants
      derived from M. bovis PG45 showed reduced susceptibility to tylosin and
      tilmicosin and contained a nucleotide insertion within the central loop of domain
      II of rrl3 (U747-G748Ins_CU/GU or A743-U744Ins_UA), suggesting that mutations
      around G748 confer this reduced susceptibility phenotype. However, other
      Mycoplasma species containing G748A were susceptible to tylosin and tilmicosin.
      Sequence comparison with Escherichia coli revealed that M. bovis PG45 and
      isolates harbored five nucleotide alterations (U744C, G745A, U746C, A752C and
      A753G) in the central loop of domain II of 23S rRNA, whereas other Mycoplasma
      species lacked at least two of these five nucleotide alterations. It was
      therefore concluded that G748 mutations in combination with species-specific
      nucleotide alterations in the central loop of domain II of 23S rRNA are likely
      sufficient to reduce susceptibility of M. bovis to tylosin and tilmicosin.

PMID- 28504457
TI  - Electronic cigarettes, quit attempts and smoking cessation: a 6-month follow-up.
AB  - BACKGROUND AND AIMS: There is conflicting evidence that use of e-cigarettes
      promotes cessation in regular smokers, but contrasting findings may be due to
      differing definitions of vaping. The aim was to assess whether regular use of e
      cigarettes while smoking is associated with subsequent smoking cessation. DESIGN:
      Baseline internet survey with outcomes measured at 6-month follow-up. SETTING:
      All French metropolitan territory. PARTICIPANTS: A total of 2057 smokers aged 15
      85 years were recruited through an access panel and responded to a 6-month follow
      up: 1805 exclusive tobacco smokers and 252 dual users (tobacco plus regular e
      cigarette users) at baseline. MEASUREMENTS: The three outcomes assessed at 6
      months were: a minimum 50% reduction in the number of cigarettes smoked per day,
      quit attempts of at least 7 days and smoking cessation of at least 7 days at the
      time of follow-up. Logistic regressions were performed to model the three
      outcomes according to regular e-cigarette use at baseline, adjusted for socio
      economic variables and smoking behaviours. FINDINGS: Baseline dual users were
      more likely than baseline exclusive tobacco smokers to have halved cigarette
      consumption [25.9 versus 11.2%, P < 0.001, adjusted odds ratio (aOR) = 2.6,
      confidence interval (CI) = 1.8-3.8]. Dual users at baseline were also more likely
      to have made a quit attempt of at least 7 days (22.8 versus 10.9%, P < 0.001, aOR
      = 1.8, CI = 1.2-2.6). No significant difference was found for 7-day cessation
      rates at 6 months (12.5 versus 9.5%, P = 0.18, aOR = 1.2, CI = 0.8-1.9).
      CONCLUSIONS: Among people who smoke, those also using an e-cigarette regularly
      are more likely to try to quit smoking and reduce their cigarette consumption
      during the next 6 months. It remains unclear whether regular e-cigarette users
      are also more likely to stop smoking.

PMID- 28504458
TI  - The burden of diabetes self-management in children and young adults.

PMID- 28504456
TI  - Performance of mycology and histopathology tests for the diagnosis of toenail
      onychomycosis due to filamentous fungi: Dermatophyte and non-dermatophyte moulds.
AB  - Improvement of laboratory diagnosis of onychomychosis is important so that
      adequate treatment can be safely implemented. To evaluate and compare the
      performance of mycological and histopathological examinations in onychomycoses
      caused by dermatophyte and non-dermatophyte moulds. Patients with lateral/distal
      subungual onychomycosis in at least one hallux were enrolled in the protocol and
      assessed via mycological and histopathological tests. The isolation of
      filamentous fungi was considered the gold standard. Test performance was
      evaluated through sensitivity, specificity and positive and negative predictive
      values. A total of 212 patients were enrolled in the study. Direct microscopy
      (DM) was positive in 57.5% patients, and cultures in 34.4%. Among these patients,
      23.3% were positive for dermatophytes, with Trichophyton rubrum the most
      frequently isolated, and 86.3% were positive for non-dermatophytes, with
      Neoscytalidium dimidiatum predominance. Histopathology was positive in 41.0%
      samples. Direct microscopy showed better sensitivity for non-dermatophyte moulds
      (P=.000) and nail clipping was more specific for dermatophyte (P=.018).
      Histopathology of the distal nail plate is a valuable complementary tool for the
      diagnosis of onychomycosis caused by dermatophytes and direct microscopy is
      especially useful for non-dermatophyte molds.

PMID- 28504460
TI  - The cyclin dependent kinase subunit Cks1 is required for infection-associated
      development of the rice blast fungus Magnaporthe oryzae.
AB  - Cell cycle regulation is pivotal for proper cell division and cellular
      differentiation in eukaryotic cells. The central regulators that govern
      eukaryotic cell cycle progression are cyclin-dependent kinases (CDKs) and their
      partners. Here, we report that Magnaporthe oryzae CKS1 encodes a cyclin-dependent
      kinase subunit, which plays a significant role in regulation of plant infection.
      We demonstrate that CKS1 is a functional homolog of CKS1/SUC1 and can physically
      interact with the CDK protein Cdc28, and Som1, a downstream regulator of the
      cyclic AMP-dependent Protein Kinase A pathway. CKS1 deletion mutants are severely
      impaired in hyphal growth, sexual reproduction, melanin pigmentation and
      conidiogenesis. Cks1 mutants are able to form appressoria from hyphal tips, but
      these are unable to re-polarize, and rice infection is impaired. CKS1 also
      affects chitin and glucan synthase activity during cell wall differentiation and
      fungal hydrophobin function. CKS1, therefore, encodes a conserved CDK-binding
      partner, essential for appressorium-mediated plant infection by the rice blast
      fungus.

PMID- 28504461
TI  - Ocular and nasal symptoms prior to acute skin graft-versus-host disease.

PMID- 28504459
TI  - Steatosis caused by experimental periodontitis is reversible after removal of
      ligature in rats.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis may promote harmful systemic effects such
      as changes in hepatic tissues. The purpose of this study was to investigate
      whether the steatosis and oxidative stress caused by experimental periodontitis
      are reversible in the liver. MATERIAL AND METHODS: Twenty-four rats were divided
      into three groups: control, periodontitis and P20-20 (20 days with experimental
      periodontitis and 20 days without experimental periodontitis, to verify the
      reversibility of hepatic injuries). The following parameters were assessed:
      gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar
      bone loss for periodontal tissues; liver weights, histopathological scores for
      steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde,
      total cholesterol and triglyceride concentrations in hepatic tissues; and blood
      levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma
      glutaryl transferase, total cholesterol and random glucose. RESULTS: Gingival
      bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss
      parameters demonstrated the development of periodontitis. There was a significant
      reduction in the steatosis score of animals from the P20-20 group when compared
      with the periodontitis group. P20-20 group presented significantly higher
      glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol
      (both in blood and hepatic tissue) and triglyceride concentrations compared with
      the periodontitis group. For levels of aspartate aminotransferase, alanine
      aminotransferase, albumin, gamma-glutaryl transferase and random glucose, a
      significant difference between the groups was not observed. CONCLUSION: Our
      results demonstrate that the microvesicular steatosis caused by periodontitis in
      rats is reversible after removal of the ligature, which is associated with the
      increase in oxidative stress and lipid peroxidation in the liver.

PMID- 28504463
TI  - Magnetocatalytic Graphene Quantum Dots Janus Micromotors for Bacterial Endotoxin
      Detection.
AB  - Magnetocatalytic hybrid Janus micromotors encapsulating phenylboronic acid (PABA)
      modified graphene quantum dots (GQDs) are described herein as ultrafast sensors
      for the detection of deadly bacteria endotoxins. A bottom-up approach was adopted
      to synthesize an oil-in-water emulsion containing the GQDs along with a high
      loading of platinum and iron oxide nanoparticles on one side of the Janus
      micromotor body. The two different "active regions" enable highly efficient
      propulsion in the presence of hydrogen peroxide or magnetic actuation without the
      addition of a chemical fuel. Fluorescence quenching was observed upon the
      interaction of GQDs with the target endotoxin (LPS), whereby the PABA tags acted
      as highly specific recognition receptors of the LPS core polysaccharide region.
      Such adaptive hybrid operation and highly specific detection hold considerable
      promise for diverse clinical, agrofood, and biological applications and
      integration in future lab-on-chip technology.

PMID- 28504462
TI  - Endocytic activity of HIV-1 Vpu: Phosphoserine-dependent interactions with
      clathrin adaptors.
AB  - HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication
      and provide immune-evasion, triggering ubiquitin-mediated degradation of some
      targets but also modulating endosomal trafficking to deplete them from the plasma
      membrane. Interactions between Vpu and the heterotetrameric clathrin adaptor
      protein (AP) complexes AP-1 and AP-2 have been described, yet the molecular basis
      and functional roles of such interactions are incompletely defined. To
      investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic
      domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8
      alpha-chain. CD8-VpuCD was rapidly endocytosed in a clathrin- and AP-2-dependent
      manner. Multiple determinants within the Vpu CD contributed to endocytic
      activity, including phosphoserines of the beta-TrCP binding site and a leucine
      based ExxxLV motif. Using recombinant proteins, we confirmed ExxxLV-dependent
      binding of the Vpu CD to the alpha/sigma2 subunit hemicomplex of AP-2 and showed
      that this is enhanced by serine-phosphorylation. Remarkably, the Vpu CD also
      bound directly to the medium (MU) subunits of AP-2 and AP-1; this interaction was
      dependent on serine-phosphorylation of Vpu and on basic residues in the MU
      subunits. We propose that the flexibility with which Vpu binds AP complexes
      broadens the range of cellular targets that it can misdirect to the virus'
      advantage.

PMID- 28504464
TI  - Skeletal maturity of the hand in an East African group from Sudan.
AB  - OBJECTIVES: Studies of skeletal maturity from Africa indicate a delay, reflected
      in a negative relative skeletal age (RSA). This study aims to evaluate the
      influence of age, socioeconomic status (SES) and nutritional status on skeletal
      maturation in a large sample of children from North Sudan. MATERIALS: The sample
      consisted 665 males and 1018 females from 3-25 years from Khartoum. Height,
      weight, age of menarche and, SES were recorded of patients attending for dental
      treatment. METHODS: Skeletal age was assigned from hand-wrist radiographs using
      the Greulich-Pyle (GP) atlas (1952). RSA (difference between skeletal and
      chronological ages) was compared in groups divided by age, sex, height-for-age
      and body-mass-index z scores, and SES. Spearman's correlation and student t-test
      was used to compare groups. RESULTS: Delayed skeletal age was noted across all
      age in boys. In girls, a delay was observed between ages 6-10, while advancement
      occurred between ages 13-18. Maturity was delayed in low height groups (p < .05)
      and low SES groups. RSA was negatively associated with HAZ in low SES males (R = 
      0.0.27, p < .001) and low SES females (R = -0.32, p < .001). CONCLUSIONS: There
      were statistically significant skeletal delays in North Sudanese males and most
      pre-menarche females, low height and low SES groups. Post-menarche females were
      advanced relative to males and GP references. Low SES impacts were statistically
      correlated to skeletal delay.

PMID- 28504465
TI  - Effects of SA237, a humanized anti-interleukin-6 receptor monoclonal antibody, on
      pre- and postnatal development in cynomolgus monkey.
AB  - BACKGROUND: SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal
      antibody in which the constant and variable regions have been engineered for a
      longer plasma half-life. According to literature, blocking of IL-6 related
      functions could have an influence on pregnancy sustainment, development of the
      immune system, and brain growth. METHODS: SA237 effects on dams, embryo-fetal
      development, parturition and postnatal development were investigated in an
      enhanced pre- and postnatal development study, in which SA237 was subcutaneously
      administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once
      weekly from gestation day 20 until parturition. Infant development, including
      immune function and learning ability tests, was comprehensively assessed at
      multiple examinations until approximately 10 months after birth. RESULTS: SA237
      plasma concentrations were almost equivalent between dams and their infants and
      dropped throughout the postnatal period, pharmacologically relevant exposure was
      maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to
      IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams
      and infants. However, there were no SA237-related adverse effects on dams,
      embryos, fetuses, or infants. SA237 pharmacological effects contributed to the
      suppression of plasma cell differentiation and antibody production by inhibiting
      IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed
      in infants, but physiological immunoglobulin class switching and general antibody
      production against a T cell-dependent antigen were maintained. CONCLUSION: The
      exposure to SA237 did not adversely affect dams, embryo-fetal development,
      parturition, and postnatal development, including immune function and neuronal
      development. Birth Defects Research 109:843-856, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28504467
TI  - Corona[5]arenes Accessed by a Macrocycle-to-Macrocycle Transformation Route and a
      One-Pot Three-Component Reaction.
AB  - Corona[5]arenes, a novel type of macrocyclic compound that is composed of
      alternating heteroatoms and para-arylenes, were synthesized efficiently by two
      distinct methods. In a macrocycle-to-macrocycle transformation approach, S6 
      corona[3]arene[3]tetrazine underwent sequential SN Ar reactions with HS-C6 H4 -X
      C6 H4 -SH (X=S, CH2 , CMe2 , SO2 , and O) to produce the corresponding
      corona[3]arene[2]tetrazines. Different corona[3]arene[2]tetrazine compounds were
      also constructed in a straightforward manner by a one-pot three-component
      reaction of HS-C6 H4 -X-C6 H4 -SH (X=S, CH2 , CMe2 , SO2 , and O) with diethyl
      2,5-dimercaptoterephthalate and 2 equiv of 3,6-dichlorotetrazine under very mild
      conditions. All corona[5]arenes adopted 1,2,4-alternate conformational structures
      in the crystalline state yielding similar nearly regular pentagonal cavities.
      Both the cavity size and the electronic property of the acquired macrocycles were
      fine-tuned by the nature of the bridging element X.

PMID- 28504466
TI  - Nepetoidin B, a Natural Product, Inhibits LPS-stimulated Nitric Oxide Production
      via Modulation of iNOS Mediated by NF-kappaB/MKP-5 Pathways.
AB  - Previous reports showed that nepetoidin B (NTB), a natural product isolated from
      many herbs, has anti-fungal and anti-bacterial effects. In this study, the
      antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)
      stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was
      determined by MTT assay. The nitric oxide (NO) production was detected by Griess
      assay. The TNF-alpha and IL-6 levels were determined by enzyme-linked
      immunosorbent assay kits. Protein expressions were tested by western blotting.
      The transcription activity of inducible nitric oxide synthase (iNOS) was detected
      by luciferase assay. Immunofluorescence assay was used to observe the
      visualization of NF-kappaB/p65 nuclear translocation. NTB and LPS showed no
      obvious cytotoxic effect on RAW 264.7 cells. NTB remarkably inhibited LPS-induced
      NO and TNF-alpha secretion in a concentration-dependent manner while showed no
      significant effect on IL-6 secretion. NTB inhibited LPS-induced iNOS protein
      expression and transcription activity without affecting cyclooxygenase-2.
      Furthermore, NTB suppressed LPS-stimulated NF-kappaB/p65 phosphorylation and
      nuclear translocation. In addition, NTB significantly inhibited LPS-induced
      phosphorylation of JNK1/2 and p38MAPK without affecting ERK1/2. LPS-induced
      inhibition of mitogen-activated protein kinase phosphatase-5 (MKP-5) was
      completely reversed by NTB. In conclusion, these results suggested that NTB
      inhibited LPS-stimulated NO production possibly via modulation of iNOS mediated
      by MKP-5/NF-kappaB pathways in RAW 264.7 cells. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28504468
TI  - Incubatory environment of the scalp impacts pre-emergent hair to affect post
      emergent hair cuticle integrity.
AB  - OBJECTIVES: To determine whether the oxidative stress transmitted to newly grown
      hair from an unhealthy scalp has physical consequences to the cuticular condition
      and function. METHODS: A uniquely designed 24-week clinical study included 8
      weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with
      either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo
      cosmetic shampoo. This clinical design allowed the growth and acquisition of hair
      samples under conditions of varying but known scalp health as a result of
      treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary
      methods were used to characterize the integrity of the cuticular surface. Hair
      surface hydrophobicity was assessed by quantifying water wetting force using a
      Wilhelmy balance method. Surface structure and porosity were assessed using
      dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. RESULTS:
      Chemical oxidative stress to pre-emergent hair has been shown to have negative
      consequences to hair surface structure. Compared to a placebo shampoo control,
      use of a potentiated ZPT shampoo improved scalp health and significantly improved
      the following attributes associated with healthy hair: hair surface
      hydrophobicity (surface energy) and cuticular moisture barrier effectiveness
      (dynamic vapor sorption). CONCLUSIONS: Pre-emergent hair can be negatively
      impacted by the oxidative stress that occurs with an unhealthy scalp, possibly
      due to metabolic activity of resident microbes. Manifestations of the oxidative
      stress include altered cuticle surface properties that are responsible for its
      protective function; these effects are similar in type to those observed by
      bleaching post-emergent hair. These alterations have the potential to make the
      hair, once emerged from the scalp, more susceptible to the cumulative physical
      and chemical insults responsible for hair feel and look, fiber integrity, and
      overall retention.

PMID- 28504469
TI  - Subtle but ubiquitous selection on body size in a natural population of collared
      flycatchers over 33 years.
AB  - Understanding the magnitude and long-term patterns of selection in natural
      populations is of importance, for example, when analysing the evolutionary impact
      of climate change. We estimated univariate and multivariate directional,
      quadratic and correlational selection on four morphological traits (adult wing,
      tarsus and tail length, body mass) over a time period of 33 years (~ 19 000
      observations) in a nest-box breeding population of collared flycatchers (Ficedula
      albicollis). In general, selection was weak in both males and females over the
      years regardless of fitness measure (fledged young, recruits and survival) with
      only few cases with statistically significant selection. When data were analysed
      in a multivariate context and as time series, a number of patterns emerged; there
      was a consistent, but weak, selection for longer wings in both sexes, selection
      was stronger on females when the number of fledged young was used as a fitness
      measure, there were no indications of sexually antagonistic selection, and we
      found a negative correlation between selection on tarsus and wing length in both
      sexes but using different fitness measures. Uni- and multivariate selection
      gradients were correlated only for wing length and mass. Multivariate selection
      gradient vectors were longer than corresponding vector of univariate gradients
      and had more constrained direction. Correlational selection had little
      importance. Overall, the fitness surface was more or less flat with few cases of
      significant curvature, indicating that the adaptive peak with regard to body size
      in this species is broader than the phenotypic distribution, which has resulted
      in weak estimates of selection.

PMID- 28504470
TI  - Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four
      pregnant Chinese women.
AB  - Hantavirus infection during pregnancy can influence both maternal and fetal
      outcomes. Here, we describe four cases of hemorrhagic fever with renal syndrome
      (HFRS) in pregnant Chinese women. The HFRS put these women at increased risk for
      severe illness, despite the patients' symptomologies in the onset phase were
      similar to those observed in non-pregnant HFRS patients, such as fever, headache,
      nausea, and thrombocytopenia. Pregnant women appeared to have a more severe
      status, presenting with severe complications, such as hypervolemia and pulmonary
      edema. Nevertheless, with appropriate management, mothers with HFRS may carry to
      full-term and breastfeeding maybe safe and feasible.

PMID- 28504471
TI  - Scedosporium apiospermum complex in cystic fibrosis; should we treat?
AB  - Species of the Scedosporium apiospermum complex are the second most frequent
      filamentous fungi after Aspergillus fumigatus that can be found in cystic
      fibrosis (CF). Mixed colonisation by S. apiospermum complex and A. fumigatus is
      also quite common. In this study we summarise all CF patients who were colonised
      by S. apiospermum complex during their childhood and we present two CF patients
      who were treated as fungal bronchitis due to S. apiospermum complex. The medical
      records of 400 CF patients were reviewed in order to identify those with positive
      respiratory cultures for S. apiospermum complex. Scedosporium apiospermum complex
      was isolated in 10 CF patients and six of them had more than two positive sputum
      cultures during the study period. By the time of first isolation, the median age
      was 14.5 years, the median BMI was 19.41 kg/m2 , the median predicted FEV1 % was
      78.65% and six patients had a history of A. fumigatus isolation. Two patients
      presented symptoms of infection while they were colonised by S. apiospermum
      complex. A rapid remission of their symptoms was observed only when antifungal
      therapy was administered. Antifungal treatment should be considered in CF
      patients who present symptoms of infection not responding to antibacterial
      therapy and S. apiospermum complex is persistently growing in sputum cultures.

PMID- 28504472
TI  - Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition
      to Support Model-Informed Drug Discovery and Development.
AB  - Pharmacometric analyses are complex and multifactorial. It is essential to check,
      track, and document the vast amounts of data and metadata that are generated
      during these analyses (and the relationships between them) in order to comply
      with regulations, support quality control, auditing, and reporting. It is,
      however, challenging, tedious, error-prone, and time-consuming, and diverts
      pharmacometricians from the more useful business of doing science. Automating
      this process would save time, reduce transcriptional errors, support the
      retention and transfer of knowledge, encourage good practice, and help ensure
      that pharmacometric analyses appropriately impact decisions. The ability to
      document, communicate, and reconstruct a complete pharmacometric analysis using
      an open standard would have considerable benefits. In this article, the
      Innovative Medicines Initiative (IMI) Drug Disease Model Resources (DDMoRe)
      consortium proposes a set of standards to facilitate the capture, storage, and
      reporting of knowledge (including assumptions and decisions) in the context of
      model-informed drug discovery and development (MID3), as well as to support
      reproducibility: "Thoughtflow." A prototype software implementation is provided.

PMID- 28504473
TI  - Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to
      Epithelial Cells.
AB  - Pathogens frequently rely on lectins for adhesion and cellular entry into the
      host. Since these interactions typically result from multimeric binding of
      lectins to cell-surface glycans, novel therapeutic strategies are being developed
      with the use of glycomimetics as competitors of such interactions. Herein we
      study the benefit of nucleic acid based oligomeric assemblies with PNA-fucose
      conjugates. We demonstrate that the interactions of a lectin with epithelial
      cells can be inhibited with conjugates that do not form stable assemblies in
      solution but benefit from cooperativity between ligand-protein interactions and
      PNA hybridization to achieve high affinity. A dynamic dimeric assembly fully
      blocked the binding of the fucose-binding lectin BambL of Burkholderia ambifaria,
      a pathogenic bacterium, to epithelial cells with an efficiency of more than 700
      fold compared to l-fucose.

PMID- 28504474
TI  - A Simple Post-Polymerization Modification Method for Controlling Side-Chain
      Information in Digital Polymers.
AB  - A three-step post-polymerization modification method was developed for the design
      of digitally encoded poly(phosphodiester)s with controllable side groups.
      Sequence-defined precursors were synthesized, either manually on polystyrene
      resins or automatically on controlled pore glass supports, using two
      phosphoramidite monomers containing either terminal alkynes or triisopropylsilyl
      (TIPS) protected alkyne side groups. Afterwards, these polymers were modified by
      stepwise copper-catalyzed azide-alkyne cycloaddition (CuAAC). The terminal
      alkynes were first reacted with a model azide compound, and after removal of the
      TIPS groups, the remaining alkynes were reacted with another organic azide. This
      simple method allows for quantitative side-chain modification, thus opening up
      interesting avenues for the preparation of a wide variety of digital polymers.

PMID- 28504475
TI  - MAP3K1-related gonadal dysgenesis: Six new cases and review of the literature.
AB  - Investigation of disorders of sex development (DSD) has resulted in the discovery
      of multiple sex-determining genes. MAP3K1 encodes a signal transduction regulator
      in the sex determination pathway and is emerging as one of the more common genes
      responsible for 46,XY DSD presenting as complete or partial gonadal dysgenesis.
      Clinical assessment, endocrine evaluation, and genetic analysis were performed in
      six individuals from four unrelated families with 46,XY DSD. All six individuals
      were found to have likely pathogenic MAP3K1 variants. Three of these individuals
      presented with complete gonadal dysgenesis, characterized by bilateral streak
      gonads with typical internal and external female genitalia, while the other three
      presented with partial gonadal dysgenesis, characterized by incomplete testicular
      development, resulting in clitoral hypertrophy with otherwise typical female
      external genitalia. Testing for MAP3K1 variants should be considered in patients
      with 46,XY complete or partial gonadal dysgenesis, particularly in families with
      multiple members affected with 46,XY DSD. Identification of a MAP3K1 variant
      should prompt an evaluation for DSD in female siblings of the proband.

PMID- 28504477
TI  - Corrigendum.

PMID- 28504476
TI  - Thirty years of interferon-tau research; Past, present and future perspective.
AB  - The year 2017 marks the 30th year since the discovery was made of amino acid and
      complementary DNA sequences of ovine trophoblast protein-1 (oTP-1), later renamed
      as interferon-tau (IFNtau). Ovine TP-1 was originally found as a secretory
      product of sheep conceptuses that rescues maternal corpus luteum (CL) and in
      fact, the uterine infusion of oTP-1 extended inter-estrous intervals. Finding
      this signaling molecule as an IFN-like sequence was surprising to the scientific
      community in reproduction because a homologous molecule in humans possesses anti
      viral and anti-prolific activity and is often used in human medicines. However,
      since its discovery was made, large efforts have been made in the elucidation of
      transcriptional regulation and functions of bovine and ovine IFNtaus, more
      importantly, the improvement of pregnancy rates in sheep and cattle, most of
      which resulted in unsuccessful outcomes. In this review, physiological, cellular
      and molecular events associated with continued secretion of progesterone,
      maternal recognition of pregnancy, identification, transcriptional regulation and
      function of IFNtau, and its future perspectives will be discussed.

PMID- 28504478
TI  - Reduced egg shell permeability affects embryonic development and hatchling traits
      in Lycodon rufozonatum and Pelodiscus sinensis.
AB  - The response of embryos to unpredictable hypoxia is critical for successful
      embryonic development, yet there remain significant gaps in our understanding of
      such responses in reptiles with different types of egg shell. We experimentally
      generated external regional hypoxia by sealing either the upper half or bottom
      half of the surface area of eggs in 2 species of reptiles (snake [Lycodon
      rufozonatum] with parchment egg shell and Chinese soft-shelled turtle [Pelodiscus
      sinensis] with rigid egg shell), then monitored the growth pattern of the opaque
      white patch in turtle eggs (a membrane that attaches the embryo to the egg shell
      and plays an important role in gas exchange), the embryonic heart rate, the
      developmental rate and the hatchling traits in turtle and snake eggs in response
      to external regional hypoxia. The snake embryos from the hypoxia treatments
      facultatively increased their heart rate during incubation, and turtle embryos
      from the upper-half hypoxia treatment enhanced their growth of the opaque white
      patch. Furthermore, the incubation period and hatching success of embryos were
      not affected by the hypoxia treatment in these 2 species. External regional
      hypoxia significantly affected embryonic yolk utilization and offspring size in
      the snake and turtle. Compared to sham controls, embryos from the upper-half
      hypoxia treatment used less energy from yolk and, therefore, developed into
      smaller hatchlings, but embryos from the bottom-half hypoxia treatment did not.

PMID- 28504479
TI  - Contribution of anthocyanin-rich foods in obesity control through gut microbiota
      interactions.
AB  - Obesity is characterized by low-grade inflammation and a number of metabolic
      disorders. Distal gut microbes' content (microbiota) is not yet fully understood
      but evidence shows that it is influenced by internal and external factors that
      modulate its composition and function. The evidence that gut microbiota
      composition can differ between healthy and obese individuals, as well as for
      those who maintain specific dietary habits, has led to the study of this
      environmental factor as a key link between the pathophysiology of obesity and gut
      microbiota. Data obtained about the role of anthocyanins (ACNs) in microbiota may
      lead to different strategies to manipulate bacterial populations and promote
      health. Anthocyanins have been identified as modulators of gut microbiota that
      contribute to obesity control and these bioactive compounds should be considered
      to have a prebiotic action. This review addresses the relevance of knowledge
      about the influence of anthocyanins-rich food consumption on microbiota, and
      their health-promoting potential in the pathophysiology of obesity. (c) 2017
      BioFactors, 43(4):507-516, 2017.

PMID- 28504480
TI  - Therapeutic effect of microneedling and autologous platelet-rich plasma in the
      treatment of atrophic scars: A randomized study.
AB  - BACKGROUND: New treatments and techniques were being added over the last few
      years to treat atrophic scars with variable results and adverse effects. AIM OF
      THE WORK: The aim of this study was to evaluate and compare the therapeutic
      efficacy and safety of microneedling, autologous platelet-rich plasma, and
      combination of both procedures in the treatment of atrophic scars. PATIENTS AND
      METHODS: This study included 90 patients with atrophic scars and were classified
      randomly into three groups: I: 28 patients treated with microneedling, one
      session every 4 weeks; II: 34 patients treated with intradermal injection of
      platelet-rich plasma, one session every 2 weeks; and III: 28 patients treated
      with alternative sessions of each microneedling and platelet-rich plasma, 2 weeks
      between each session, for a maximum of six sessions. RESULTS: There was a
      statistically significant improvement in the appearance of atrophic scars, with
      reduction in the scores associated with the clinical evaluation scale for
      atrophic scarring in all groups, but the improvement was more obvious in group
      III. CONCLUSIONS: Although a single treatment may give good results, combination
      between skin needling and platelet-rich plasma is more effective, safe with less
      number of sessions in all types of atrophic scars.

PMID- 28504481
TI  - Comprehensive mass cytometry analysis of cell cycle, activation and co-inhibitory
      receptors expression in CD4 T cells from healthy and HIV-infected individuals.

PMID- 28504482
TI  - Asymmetric Copper-Catalyzed Carbomagnesiation of Cyclopropenes.
AB  - The highly diastereo- and enantioselective formation of polysubstituted
      cyclopropanes was easily achieved through the asymmetric copper-catalyzed
      carbomagnesiation reaction of nonfunctionalized cyclopropene derivatives. The
      carbometalated species generated in situ readily undergo C-C and C-X bond-forming
      reactions with various electrophiles with complete retention of configuration.

PMID- 28504484
TI  - Disclosing errors to patients and parents, and apologizing.

PMID- 28504483
TI  - Comparison of a New Intranasal Naloxone Formulation to Intramuscular Naloxone:
      Results from Hypothesis-generating Small Clinical Studies.
AB  - Easy-to-use naloxone formulations are needed to help address the opioid overdose
      epidemic. The pharmacokinetics of i.v., i.m., and a new i.n. naloxone formulation
      (2 mg) were compared in six healthy volunteers. Relative to i.m. naloxone,
      geometric mean (90% confidence interval [CI]) absolute bioavailability of i.n.
      naloxone was modestly lower (55%; 90% CI, 43-70% vs. 41%; 90% CI, 27-62%),
      whereas average (+/-SE) mean absorption time was substantially shorter (74 +/-
      8.8 vs. 6.7 +/- 4.9 min). The opioid-attenuating effects of i.n. naloxone were
      compared with i.m. naloxone (2 mg) after administration of oral alfentanil (4 mg)
      to a separate group of six healthy volunteers pretreated with 240 mL of water or
      grapefruit juice. The i.m. and i.n. naloxone attenuated miosis by similar extents
      after water (40 +/- 15 vs. 41 +/- 21 h*%) and grapefruit juice (49 +/- 18 vs. 50
      +/- 22 h*%) pretreatment. Results merit further testing of this new naloxone
      formulation.

PMID- 28504485
TI  - Emotional exhaustion is associated with work related stressors: a cross-sectional
      multicenter study in Malaysian public hospitals.
AB  - INTRODUCTION: Emotional exhaustion is an important component of burnout. Burnout
      is common among doctors. It affects the physical and mental health of doctors,
      their performance and the quality of care they provide. This study aimed to
      investigate the level and factors associated with emotional exhaustion among
      doctors in pediatric practice in Malaysia. POPULATION AND METHODS: A self
      administered questionnaire was used in this multicenter cross-sectional study. It
      included questions on the socio-demographics, work characteristics, Emotional
      Exhaustion, Perceived Stress Scale and sources of job stress. Descriptive,
      univariate and multivariate analysis were conducted using the SPSS software.
      RESULTS: A total of 197 doctors working in the Pediatric department in eight
      hospitals returned complete questionnaire. High and moderate emotional exhaustion
      was reported by 25.4% and 24.4% doctors, respectively. In bivariate analysis, 29
      out of the 38 items of sources of stress showed significant association with
      emotional exhaustion (p <0.05).The significant predictors of emotional exhaustion
      in the multivariate analysis were: scoring higher on the Perceived Stress Score,
      dealing with patient's psychosocial problems, disrespectful interactions with
      colleagues/ subordinates, lack of appreciation from supervisors, lack of
      incentives and promotions, time pressures and deadlines to meet, and setting
      unrealistic goals of having them imposed on oneself (p <0.05). The most common
      source of stress was dealing with difficult parents (80.2%). CONCLUSIONS:
      Emotional exhaustion is associated with sources of stress in the workplace but
      not with socio-demographic factors.

PMID- 28504486
TI  - High prevalence of vitamin D deficiency among children with chronic kidney
      disease and kidney transplant.
AB  - INTRODUCTION: Vitamin D (25(OH)D) deficiency is common among patients with
      chronic kidney disease (CKD). Our objective was to establish the prevalence of
      25(OH)D deficiency among children with CKD and identify risk factors. A
      correlation was observed between 25(OH)D and parathormone intact molecule.
      POPULATION AND METHODS: Cross-sectional study conducted between January 2013 and
      December 2015. Patients younger than 19 years old with and without CKD were
      included. RESULTS: One hundred and sixty-seven patients were included. Group 1
      (healthy controls): 32 participants; group 2 (stage 2-4 CKD, glomerular
      filtration rate between 89 and 15 mL/min/1.73 m2): 34 patients; group 3 (stage 5
      CKD, dialysis): 46 patients; and group 4 (kidney transplant recipients): 55
      patients. Deficiency of 25(OH)D was detected in 12.5% of healthy controls and 32%
      of CKD patients (p= 0.025). Also, 23% of patients in group 2, 51% in group 3, and
      22% in group 4 had 25(OH)D deficiency; the mean 25(OH)D level of dialysis
      patients was significantly lower than that of the rest of the groups. Predictors
      of 25(OH)D deficiency included hypoalbuminemia, advanced CKD, and place of origin
      from the Northwest region of Argentina. The parathormone intact molecule was
      significantly higher in the group of patients with deficiency and was inversely
      correlated with 25(OH)D levels. CONCLUSION: Among CKD patients, 32% had 25(OH)D
      deficiency, which reached 51% among those with stage 5 CKD (dialysis). Predictors
      of deficiency included hypoalbuminemia, advanced CKD, and place of origin from
      the Northwest region of Argentina.

PMID- 28504487
TI  - Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of
      experience in a children's hospital.
AB  - INTRODUCTION: Haemophilus influenzae type B (Hib) used to be the main cause of
      bacterial meningitis in children younger than 5 years old. Following the
      introduction of the Hib vaccine in the immunization schedule (1998), its
      incidence reduced significantly but it has increased over the last years. The
      objectives of this study included describing the characteristics and analyzing
      the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing
      the pre- and postimmunization periods. MATERIALS AND METHODS: Time-series study.
      All patients hospitalized with Hib meningitis at Hospital de Ninos "R. Gutierrez"
      (January 1992-May 2016). Hospitalization rates were compared before (pre
      immunization) and after (post-immunization) the introduction of the Hib vaccine.
      The post-immunization period was divided into three similar periods. RESULTS:
      Eighty-five patients with Hib meningitis were admitted (73.3% in the pre
      immunization period). No differences were observed in relation to the clinical
      and sociodemographic characteristics of cases in both periods. Pre-immunization:
      10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has
      increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n=
      15): 40% had completed their primary immunization schedule, 40% were delayed on
      the immunization schedule for their age. Overall reduction in the hospital rate
      of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in
      the post-immunization period. The analysis of the different post-immunization
      periods shows a decline in reduction over time. CONCLUSIONS: A very significant
      reduction in hospitalizations due to Hib meningitis was observed after the Hib
      vaccine was introduced; however, over the past years, the number of cases has
      increased although no changes have been observed in patient characteristics.

PMID- 28504488
TI  - Argentine references for the assessment of body proportions from birth to 17
      years of age.
AB  - INTRODUCTION: Abnormal body proportions may indicate skeletal disorders;
      therefore, their detection has great clinical significance. OBJETIVES: To
      estimate centiles for head circumference/height (HC/H) and sitting height/height
      (SH/H) ratios, and assess their diagnostic usefulness among a group of children
      with skeletal dysplasia. METHODS: Centiles 3, 10, 25, 50, 75, 90 and 97 for HC/H
      and SH/H ratios were estimated with the LMS method using Box-Cox transformation
      to normalize data distribution for each age. Q-Q plot tests were applied to
      evaluate normality of residuals and the Q test to calculate goodness-of-fit.
      RESULTS: The sample included 4818 girls and4803 boys, all healthy, between 0-17
      years old. The median of the SH/H ratio for each age decreased from 0.67 at birth
      to 0.57 at age 4. At 12 years of age, values reached 0.52 and 0.53 for males and
      females, respectively, remaining unchanged until age 17. The median of the HC/H
      ratio decreased from 0.45 at 6 years old to 0.34 at 17 years old for both sexes.
      Z-scores for SH/H among 20 children diagnosed with hypochondroplasia were better
      at showing abnormal proportions than the SH/H ratio not adjusted by age.
      CONCLUSIONS: Estimated centiles for HC/H and SH/H ratios show that the most
      dramatic changes in body proportions occur in the prepubertal period. These
      references allow an earlier detection of abnormal body proportions in children
      with skeletal dysplasia.

PMID- 28504489
TI  - Psychometric properties of scales used for grading the severity of bronchial
      obstruction in pediatrics: A systematic review and meta-analysis.
AB  - INTRODUCTION: In pediatrics, identifying the severity of bronchial obstruction in
      an early manner is a decisive factor. OBJETIVE: To assess the psychometric
      properties of the scales for grading the severity of bronchial obstruction in
      pediatric patients. POPULATION AND METHOD: This was a systematic review of
      studies on the validity and reliability of scales for grading the severity of
      bronchial obstruction conducted in infants and children younger than 3 years old.
      The search was conducted in Medline, WoS, EMBASE, SciELO, and Google Scholar. The
      correlation coefficient corresponding to each article was included in a random
      effects model to establish the criterion validity and reliability using the
      weighted averages of coefficients as per the sample size. RESULTS: A total of 9
      articles were included, which accounted for 2699 children; 3 articles had an
      adequate or excellent methodological quality. Four articles established the
      concurrent criterion validity considering oxygen saturation, with a weighted
      correlation coefficient of -0.627 (95% confidence interval [CI]: -0.767 to 
      0.431, p < 0.001); 2 articles established the convergent criterion validity, with
      a weighted correlation coefficient of 0.809 (95% CI: 0.721 to 0.871, p < 0.001);
      6 articles established the inter-observer reliability, with a weighted
      correlation coefficient of0.500for kappa and 0.891 for the intraclass correlation
      coefficient. CONCLUSION: The assessment of psychometric properties to support the
      use of scales for grading the construct "severity of bronchial obstruction"
      showed a moderate to adequate criterion validity. The percentage of agreement
      among observers in terms of the studied measure (severity of bronchial
      obstruction) was adequate; however, weaknesses such as the article design should
      be taken into account since it may affect the internal validity of results.

PMID- 28504490
TI  - Additive effect of mesenchymal stem cells and defibrotide in an arterial rat
      thrombosis model.
AB  - BACKGROUND/AIM: In this study, we aimed to investigate the additive effect of
      mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral
      arterial thrombosis. METHODS: Thirty Sprague Dawley rats were included. An
      arterial thrombosis model by ferric chloride (FeCl3) was developed in the left
      femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated
      (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected;
      Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal
      injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd
      one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd
      injection. RESULTS: Although the use of human bone marrow-derived (hBM) hBM-MSC
      or DFT alone enabled partial resolution of the thrombus, combining them resulted
      in near-complete resolution. Neovascularization was two-fold better in hBM-MSC +
      DFT treated rats (11.6 +/- 2.4 channels) compared with the hBM-MSC (3.8 +/- 2.7
      channels) and DFT groups (5.5 +/- 1.8 channels) (P < 0.0001 and P= 0.002,
      respectively). CONCLUSION: The combined use of hBM-MSC and DFT in a rat model of
      arterial thrombosis showed additive effect resulting in near-complete resolution
      of the thrombus.

PMID- 28504491
TI  - Profile of spontaneous demand for services among infants younger than 30 days old
      at a children's tertiary care hospital.
AB  - INTRODUCTION: In recent years, admission of critical newborn infants (NBIs) to
      the neonatal intensive care unit of Hospital Garrahan (HG) has been limited due
      to the hospitalization of infants younger than 30 days old through spontaneous
      demand for services. This is probably a multifactorial situation, and one of its
      causes is a lack of regionalization, which results in an inadequate use of
      resources or a distorted use of resources intended for more complex care.
      OBJECTIVE: To establish the profile of NBIs who make a spontaneous demand for
      services at HG and to assess the level of care required based on their medical
      condition. MATERIALS AND METHODS: Cross-sectional study. All infants < 30 days
      old who sought care at HG in a period of 12 months were assessed. The analysis
      included clinical characteristics of NBIs, prior visits, parental reason for
      consultation at HG, and whether NBIs could have been seen at a primary or
      secondary care facility. RESULTS: A total of 307 consultations were analyzed; NBI
      age was 18 days +/- 7.6. Of these, 78% required hospitalization. The most common
      reason for hospitalization was acute respiratory tract infection. Thirty-five
      percent had health insurance coverage; 54% had sought care more than once at a
      different facility. Only 15% of NBIs had a highly complex condition that should
      have actually been solved at HG. CONCLUSION: Based on the analysis of NBIs seen
      at HG through spontaneous demand for services, a high requirement of
      hospitalization for low and medium complexity pathologies was observed.

PMID- 28504492
TI  - Salivary and serum cortisol levels in newborn infants.
AB  - INTRODUCTION: Given that serum cortisol level interpretation in newborn infants
      (NBIs) is hard, the objective of this study was to correlate baseline salivary
      and serum cortisol levels and to describe salivary cortisol levels in the first
      month of life. POPULATION AND METHODS: Descriptive, prospective, longitudinal,
      and correlational study. Term NBIs were selected from the Division of Neonatology
      of Hospital Nacional Profesor Alejandro Posadas in 2014. Cortisol was measured in
      saliva specimens while cortisol, cortisol-binding globulin, and albumin were
      measured in blood specimens. A linear correlation was performed to relate serum
      and salivary cortisol levels; Friedman test was conducted to compare cortisol
      levels during the first month of life, and the difference was used to analyze the
      performance of values equal to or lower than the first quartile. RESULTS: Fifty
      five NBIs were studied. Serum cortisol: 7.65 (1.0-18.1 gg/dL); salivary cortisol:
      35.88 (5.52-107.64 mmol/L); cortisol-binding globulin: 22.07 (16.5-33.0 gg/mL),
      expressed as median and range. The correlation coefficient between serum and
      salivary cortisol was 0.54, P = 0.001. Cortisol performance during the first
      month of life showed no statistically significant differences, and the difference
      between the second and the first specimen of values equal to or lower than the
      first quartile increased in 10 out of 12 patients. CONCLUSION: The measurement of
      cortisol in saliva reflects serum cortisol levels in normal NBIs. Some patients
      had low levels of cortisol at 36 hours of life and showed a trend towards a
      spontaneous increase during the first month of life.

PMID- 28504493
TI  - Neuropsychological assessment among children and adolescents with phenylketonuria
      and hyperphenylalaninemia and its relationship with plasma phenylalanine levels.
AB  - Although with early treatment phenylketonuria patients may have average
      intelligence levels, it is important to optimize the nutritional management to
      maintain adequate phenylalanine levels, so that patients can develop their
      intellectal potential free of abnormalities in their daily activities due to
      deficits of cognitive executive functions. This study presents a series of 26
      patients, diagnosed and treated early, who underwent a psychometric evaluation
      together with phenylalanine determinations along their lives, and at the time of
      doing the tests. A trend is observed towards a reverse relationship between IQ
      and concurrent phenylalanine concentration, phenylalanine median and
      phenylalanine/tyrosine ratio. Likewise, a trend towards a negative relationship
      is observed between executive functions and concurrent phenylalanine values along
      patients' lives.

PMID- 28504494
TI  - Staphylococcus aureus nasal carriage and its antibiotic resistance profiles in
      children in high altitude areas of Southwestern China.
AB  - BACKGROUND/AIM: To describe the epidemiological profile of nasal carriage of
      Staphylococcus aureus (S. aureus) strains, its antibiotic resistance and mecA and
      Panton Valentine leukocidin (PVL) genes presence, in school children residing in
      high altitude areas of Southwestern China. METHODS: The cross sectional study
      screened nasal swabs taken from students for S.aureus. PCR was performed to
      identify mecA and PVL genes. RESULTS: Of the total 314 children 5.10% (16/314)
      was detected S.aureus. The resistance of isolated strains to penicillin,
      erythromycin, clindamycin, rifampicin and cefoxitin was 100%, 81.3%, 81.3%, 0.0%,
      and 6.3% respectively. No strains demonstrated resistance to vancomycin;
      expression of mecA gene was detected in 3 isolates and 10 isolates were PVL
      positive. CONCLUSION: S. aureus was detected in 5.10% (16/314) of the study
      population; 0.96% (3/314) had methicillin resistant S.aureus (MRSA); expression
      of the mecA and PVL genes were detected in 3 and 10 isolates respectively.

PMID- 28504495
TI  - Early use of continuous positive airway pressure in the treatment of moderate to
      severe acute lower respiratory tract infections among patients younger than 2
      years old.
AB  - OBJETIVE: To analyze the characteristics of patients younger than 2 years old who
      had a moderate to severe acute lower respiratory tract infection and were treated
      early with bubble continuous positive airway pressure, and factors associated
      with a successful intervention. METHOD: Retrospective and descriptive study.
      Children younger than 2 years old admitted to the Pediatric Intermediate Care
      Unit of Hospital Provincial Neuquen between June 2009 and December 2010. Bubble
      continuous positive airway pressure was used, and the following outcomes were
      measured: heart rate, respiratory rate, Tal's score, oxygen saturation, and
      fraction of inspired oxygen at 0, 2, 6, 24, and 48 h. RESULTS: One hundred and
      twenty patients were included. Their median age was 3 months old. The
      intervention was successful in 72% of patients. At 2 h, a 15% reduction in
      respiratory rate, and a 2-point decrease in Tal's score were predictors of
      success, with an odds ratio of 6.41 (95% confidence interval: 2.68-15.36), and of
      9.07 (95% confidence interval: 3.72-22.19), respectively. CONCLUSIONS: A
      reduction in respiratory rate, heart rate, and Tal's score at 2 hours of starting
      the intervention were predictors of success.

PMID- 28504496
TI  - Echinococcosis in children: Experience in a tertiary care hospital outside the
      endemic area.
AB  - Echinococcosis is a zoonotic disease that is widely spread across Argentina and
      worldwide. It is acquired during childhood but it is more common during
      adulthood. The pediatric population accounts for 10-20% of all cases. This study
      included 47 children diagnosed with echinococcosis over a 20-year period. Their
      median age was 8 years old (range: 3-17); most patients had some epidemiological
      history, such as having lived or living in an endemic or rural area and/ or
      having dogs that are fed with viscera. Findings included 85% of single cysts in
      only one parenchyma. Cysts were most commonly located in the liver and lungs.
      Medical/surgical treatment was carried out in 45 patients (96%). Subsequent
      complications were observed in 13 patients (28%), which were more common in those
      with lung cysts. Three patients (6%) relapsed 1-24 months later and required a
      new surgery. No patient died as a result of the parasitic disease.

PMID- 28504497
TI  - Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase
      deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An
      update.
AB  - Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic
      disease with significant morbidity and mortality in children and adults. This
      document provides guidance on when to suspect LAL-D and how to diagnose it. It is
      recommended to add lysosomal acid lipase deficiency to the List of differential
      diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea,
      chronic malnutrition, and hemophagocytic lymphohistiocytosis. It should also be
      considered in young patients with dyslipidemia and atherosclerosis as well as
      diseases associated with fatty liver and/or hepatomegaly. LAL-D should be
      suspected in patients with hepatomegaly, hyperlipidemia and /or elevated
      transaminases found during routine checks or testing for other conditions, and in
      patients with cryptogenic cirrhosis. At present, there is the option of a
      specific enzyme replacement treatment.

PMID- 28504498
TI  - [Pediatric case report: Spinal epidural abscess].
AB  - Spinal epidural abscess is an uncommon pathology. It has an incidence of one case
      per 100 000 individuals. An increase is observed due to the raise of risk factors
      such as diabetes mellitus, spinal abnormalities, tattoos, acupuncture, epidural
      analgesia, and a greater availability of imaging methods. It is a purulent
      collection located between the dura and the medullary canal. The most common
      germs are Staphylococcus aureus and Gram-negative bacteria. Without timely
      treatment, it evolves to medullary compression and permanent neurological
      sequelae. An 11-year-old girl was admitted with fever of 48 hs evolution, left
      lower back pain, antalgic gait with lumbar stiffness. Neurological examination
      was normal. Blunt blistering lesions were observed on lower limbs. Magnetic
      resonance imaging showed an image compatible with spinal epidural abscess. The
      evolutionwas favorable. Treatment consisted of surgical drainage and antibiotics
      for 6 weeks. From the culture of the material obtained, methidllin-sensitive
      Staphylococcus aureus was isolated.

PMID- 28504499
TI  - [Transverse vaginal septum diagnosed in sisters. Cases report].
AB  - Transverse vaginal septum is a disorder that would arise from a failure in the
      fusion and/or channeling of the urogenital sinus and the mullerian ducts with low
      frequency but with a significant impact on the health of patients. The treatment
      is surgical and it will depend on the location and thickness of the septum.
      Sometimes, it described a female sex-limited autosomal recessive transmission but
      few cases of family association have been reported. We present the cases of two
      sisters who had this rare entity 5 years apart and were diagnosed by the
      presentation of an intense hypogastric abdominal pain at the age of 11 and 12
      years when they had a Tanner stage III pubertal development and primary
      amenorrhea.

PMID- 28504500
TI  - Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2
      mutation: a case report.
AB  - BACKGROUND: Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known
      as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural
      hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into
      the cells results from homozygous or compound heterozygous mutations in the
      SLC19A2 gene. CASE PRESENTATION: We report a girl which presented with
      sensorineural deafness treated with a hearing prosthesis, insulin requiring
      diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level
      improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day.
      CONCLUSION: Patients with TRMA must be evaluated for megaloblastic anemia,
      sensorineural hearing loss, and diabetes mellitus. They must be followed for
      response of hematologic and diabetic after thiamine therapy. It should be kept in
      mind that dose of thiamine therapy may be increased according to the clinical
      response. Genetic counseling should be given.

PMID- 28504501
TI  - [Bowel obstruction by hamartomatous polyp in a pediatric patient with tuberous
      sclerosis].
AB  - Tuberous sclerosis is an autosomal dominant disorder with a wide clinical
      spectrum of disease. It is characterized by development of benign tumors in
      multiple organs due to a disturbance in cellular growth and differentiation. It
      usually affects skin, brain, heart and kidney. Gastrointestinal involvement is
      rare and mainly restricted to adults and sigmoid colon and rectum. In children
      there are only two cases; our patient would be the third. We present a patient
      with tuberous sclerosis who began at the first month of life with repeated
      intestinal subocclusion. The videocolonoscopy showed a mass protruding into the
      lumen of the ascending colon. Right hemicolectomy was performed. The
      anatomopathological report corresponded to a hamartomatous polyp. The clinical
      and nutritional evolution in the postoperative period was very favorable.
      Although uncommon, the hamartomatous polyp should be considered in the
      differential diagnosis of intestinal occlusion in pediatrics.

PMID- 28504502
TI  - [Transient congenital hypothyroidism due to biallelic defects of DUOX2 gene. Two
      clinical cases].
AB  - Congenital hypothyroidism affects 1:2000-3000 newborns detected by neonatal
      screening programs. Dual oxidases, DUOX1 and 2, generate hydrogen peroxide needed
      for the thyroid hormone synthesis. Hipotiroidismo congenito transitorio por
      defectos bialelicos del gen DUOX2. Dos casos clinicos Transient congenital
      hypothyroidism due to biallelic defects of DUOX2 gene. Two clinical cases
      Mutations in the DUOX2 gene have been described in transient and permanent
      congenital hypothyroidism. Two brothers with congenital hypothyroidism detected
      by neonatal screening with eutopic gland and elevated thyroglobulin are
      described. They were treated with levothyroxine until it could be suspended in
      both during childhood, assuming the picture as transient. Organification disorder
      was confirmed. Both patients were compounds heterozygous for a mutation in exon 9
      of the paternal allele (c.1057_1058delTT, p.F353PfsX36 or p.F353fsX388) and in
      exon 11 of the maternal allele (c.1271T > G, p.Y425X) of DUOX2 gene. Our finding
      confirms that the magnitude of the defect of DUOX2 is not related to the number
      of inactivated alleles, suggesting compensatory mechanisms in the peroxide
      supply.

PMID- 28504503
TI  - [Cervicofacial actinomycosis as differential diagnosis of cavum carcinoma: case
      report].
AB  - Paediatric actinomycosis is an infrequent infectious disease caused by
      Actinomyces spp. Cervicofacial infections are usually related to disruption in
      oral mucosal membranes. We discuss the case of a 15-year-old girl who refers an 8
      month history of odynophagia and changes in her tone of voice after getting a
      tongue piercing. She received multiple antibiotic treatments with slight
      improvement. Nasopharyngeal carcinoma was diagnosed by endoscopic biopsy. The
      patient was referred to our Hospital for treatment but, when the biopsy was
      analyzed again, oncological pathology was excluded and oropharyngeal
      actinomycosis was diagnosed. She received a total of 6 months of antibiotic
      treatment with favorable evolution. While oral piercings have not been yet
      described as a risk factor for oropharyngeal actinomycosis, the mucosal
      disruption could favor the onset of this disease.

PMID- 28504504
TI  - [Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual
      association. Clinical case].
AB  - Cornelia de Lange syndrome is a genetic disease characterized by distinctive
      facial features, failure to thrive, microcephaly and several malformations
      associated. Its main endocrinological features are anomalies of the genitalia. We
      present a 13-year-old boy, who suffered from complicated aspiration pneumonia and
      showed Cornelia de Lange syndrome phenotype, with global developmental delay,
      suction-swallowing abnormalities, short stature and abnormal genitalia
      associated. His bone age was delayed, so he underwent full endocrinological
      panel. Central hypothyroidism, growth hormone deficiency and low luteinizing
      hormone-follicle-stimulating hormone levels were observed and multiple pituitary
      hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic
      hormone and prolactin levels were normal. He received thyroid hormonal
      substitution. Multiple pituitary hormone deficiencies are an unusual feature of
      De Lange syndrome. We suggest evaluating all different endocrine axes in these
      patients.

PMID- 28504505
TI  - Retinovascular findings in newborns with critical congenital heart disease: A
      case series.
AB  - Critical congenital heart disease (CCHD) may cause changes in retinal
      vasculature. However, there is lack of data in this issue in newborns. We
      evaluated retinovascular changes in a series of 43 newborn with CCHD. They were
      divided into 2 groups according to the type of CCHD; group 1 (n= 18): left
      obstructive CCHD and group 2 (n= 25): right obstructive CCHD. Retinovascular
      pathologies were detected in 21 patients (48.8%); it was more frequent in group 1
      (p= 0.04). The most common pathology was retinal vascular tortuosity in 6
      patients (33.3%) of group 1, and 4 (16.0%) in group 2. None of 21 patients with
      retinovascular changes required any therapy at follow-up. In multivariate
      analysis, only having a left obstructive CCHD was associated with the development
      of any retinovascular pathology (P= 0.03, OR: 2.8, CI95%: 1.1-7.4).
      Retinovascular changes are frequent in newborn patients with CCHD.

PMID- 28504506
TI  - [A very rare cause of peripheral precocious puberty in a girl: ovarian sex cord
      tumor with annular tubules].
AB  - Sex cord tumor with annular tubules is an extremely uncommon gonadal stromal
      neoplasm. It represents 0.05-0.6% of all ovarian tumors, according to series. An
      unusual case is presented in a 6-year-old girl, detected as a result of an
      isosexual peripheral precocious puberty. The highlight of this case is that no
      mass attached to the ovary was found, but only a gonadal asymmetry without
      radiological signs of malignancy. After confirming the presence of tumoral cells
      by intraoperative biopsy, unilateral salpingo-oophorectomy with ipsilateral para
      aortic and pelvic lymphadenectomy was performed. Afterwards, the evolution of the
      patient was favorable.

PMID- 28504507
TI  - [Mosaic trisomy 18. Series of cases].
AB  - Trisomy 18 syndrome (T18) is a clinical and genetic disorder, which has a full
      extra chromosome 18 in each cell, variant that is called free trisomy. In
      addition, it can occur in partial and mosaic form. It is characterized by
      intrauterine growth restriction, psychomotor and mental retardation,
      characteristic craniofacial findings, congenital heart disease, hypoplastic
      pelvis, clenched hand and rocker-bottom foot, among others. The mosaic T18 occurs
      when cells with T18 and normal cell lines exist in the same individual and
      correspond to 5% of cases. Trisomia 18 en mosaico. Serie de casos Mosaic trisomy
      18. Series of cases The phenotypic findings are highly variable and no
      correlation was evident between the percentage of trisomic cells and the findings
      found. The aim of this report is to present a series of five cases of mosaic T18
      with emphasis on clinical aspects in order to guide an interdisciplinary adequate
      medical care and provide timely genetic counseling.

PMID- 28504508
TI  - [Mistakes in drug prescription during simulated pediatric resuscitations and
      other urgency procedures].
AB  - INTRODUCTION: The probability of making mistakes in the prescription of medicines
      is high in pediatrics, and substantially increases in emergency situations.
      MATERIAL AND METHODS: This prospective observational study analyzed the
      prescriptions issued by physicians during 23 cardiopulmonary resuscitation
      pediatric emergency training sessions. RESULTS: During 94 simulated cases, 96
      physicians participated. Forty-four prescriptions on paper were analyzed (48%)
      including 120 doses. Twelve medication errors were found (10%, CI 95%: 5.517.2).
      Stress was identified as the primary cause of prescription mistakes. CONCLUSIONS:
      Drug prescription mistakes frequently occurred during pediatric emergency
      simulations.

PMID- 28504509
TI  - [Recommendation for therapeutic hypothermia in newborns with hypoxic-ischemic
      encephalopathy.

PMID- 28504510
TI  - [Guide for monitoring children's development in pediatric practice].
AB  - The pediatrician is the best-informed professional to whom many families look to
      be the expert, not only on childhood illnesses but also on development. Early
      identification, diagnosis and monitoring of these patients are a real challenge
      for physicians who serve children. This guide provides recommendations for
      development monitoring, evaluation, diagnosis and follow up of patients with
      developmental delays and disabilities.

PMID- 28504511
TI  - [Intrauterine growth restriction: endocrinological perspective. Update of the
      2007 version (Arch Argent Pediatr 2007;105(1):71-73)].
AB  - Most children born with low weight or intrauterine growth restriction develop
      catch-up growth that allows them to reach a final height according to their
      genetic target height. However, in about 15% of children this growth is
      insufficient. In both, children who have adequate compensatory growth and
      therefore normal height and children who remain low in childhood, it is necessary
      to take into account that if puberty starts early, the final height could be
      compromised. Timely and appropriate intervention could improve it. Control of
      body weight is also important, as an excessive gain in childhood is associated
      with metabolic complications in adolescence and adult life.

PMID- 28504512
TI  - Fully Printable Organic and Perovskite Solar Cells with Transfer-Printed Flexible
      Electrodes.
AB  - The perovskite solar cells (PSCs) and organic solar cells (OSCs) with high
      performance were fabricated with transfer-printed top metal electrodes. We have
      demonstrated that PSCs and OSCs with the top Au electrodes fabricated by using
      the transfer printing method have comparable or better performance than the
      devices with the top Au electrodes fabricated by using the conventional thermal
      evaporation method. The highest PCE of the PSCs and OSCs with the top electrodes
      fabricated using the transfer printing method achieved 13.72% and 2.35%,
      respectively. It has been investigated that fewer defects between the organic
      thin films and Au electrodes exist by using the transfer printing method which
      improved the device stability. After storing the PSCs and OSCs with the transfer
      printed electrodes in a nitrogen environment for 97 and 103 days without
      encapsulation, the PSCs and OSCs still retained 71% and 91% of their original
      PCEs, respectively.

PMID- 28504513
TI  - Photomanipulated Architecture and Patterning of Azopolymer Array.
AB  - Here reported is the approach to prepare the tunable 3D architecture and
      patterning through photoinduced orientation of azopolymer. The hemispherical
      PAzoMA array can be transformed into spindlelike, flat ellipsoidlike, thick
      spindlelike, near-hexagon, near-quadrangle, and near-rhombus arrays while being
      exposed to linearly polarized light (LPL). The size and alignment of the arrays
      can be precisely controlled by manipulating the irradiation time. Furthermore,
      complex 3D architectures of the PAzoMA array are readily fabricated through
      secondary irradiation along different direction. This technique is promising for
      functionalized surfaces and photonic devices.

PMID- 28504514
TI  - Why Life Cycle Assessment Does Not Work for Synthetic Biology.

PMID- 28504515
TI  - The Catalytically Lignan-Activation-Based Approach for the Synthesis of (epi)
      Podophyllotoxin Derivatives.
AB  - Under the effect of a catalytic amount of Au(I) complex, 4-O-(2
      cyclopropylethynyl)benzoyl-(epi)-podophyllotoxins, easily prepared via
      dehydrative condensation between (epi)-podophyllotoxin and ortho
      cyclopropylethynylbenzoic acid, could efficiently couple with a variety of
      nucleophiles including alcohol, phenol, aniline, and carbon nucleophiles, all to
      provide (epi)-podophyllotoxin derivatives. Thus, the first catalytic and lignan
      activation-based approach for (epi)-podophyllotoxin derivatization was
      established. Based on the new methodology, as well as the judicious choice of N3,
      AZMB, and Cbz protecting groups, an efficient approach forward was set. NK-611,
      an antitumoral agent at a phase II clinical trial was established, featuring an
      in situ anomerization of the hemiacetal OHs in the critical condensation step.
      Commencing from easily available starting material, the target molecule was
      obtained using the longest linear sequence of six steps and a 38% overall yield.

PMID- 28504516
TI  - Self-Associated Polyamide Alloys with Tailored Polymorphism Transition and
      Lamellar Thickening for Advanced Mechanical Application.
AB  - Long chain polyamides with various number of methylene units in recurring amide
      groups, PA1012 and PA612, were blended to combine their unique advantages. The
      Brill transition and accompanied lamellar thickening were investigated by in situ
      wide angle X-ray scattering (WAXS) and small angle X-ray scattering. From WAXS
      patterns, the transformation from the alpha- to gamma-crystalline phase, known as
      "Brill transition", can be independently observed in the constituent phases of
      the long chain polyamide alloys (LCPAs) during heating. A constant Tb (ca., 100 
      degrees C) irrespective of the blend composition and proportional variations of
      the phase content was obtained. Additionally, with elevated temperature, a
      gradual increase in both the crystalline layer (Lc) and amorphous layer (La) was
      detected in constituent polyamides. The compositional independence of the Brill
      transition in LCPAs and similar lamellar thickening originate from the complete
      immiscibility of both polyamides, which share stronger intramolecular rather than
      intermolecular hydrogen-bonding interaction and hence exhibit self-association.
      Contributed by the gamma phase, with less extended structure and increased
      lamellar thickness with compact stacking, LCPAs with controlled strength and
      flexible features can be achieved, which can be utilized in advanced mechanical
      applications, particularly for hoses of automobiles. The unusually linear
      compositional dependence of mechanical parameters makes it possible to tailor the
      polymorphic and tensile properties.

PMID- 28504517
TI  - Near-Infrared Fluorescent Turn-on Probe with a Remarkable Large Stokes Shift for
      Imaging Selenocysteine in Living Cells and Animals.
AB  - Selenocysteine (Sec) is the 21st naturally occurring amino acid and has emerged
      as an important sensing target in recent years. However, fluorescent detection of
      Sec in living systems is challenging. To date, very few fluorescent Sec probes
      have been reported and most of them respond fluorescence to Sec in the visible
      region. In this paper, a very promising near-infrared fluorescent probe for Sec
      was developed. This probe works in aqueous solution over a wide pH range under
      mild conditions and can be used for rapid, highly selective and sensitive
      detection of Sec with significant near-infrared fluorescent turn-on signal
      changes. In addition, it features a remarkable large Stokes shift (192 nm) and a
      low detection limit (60 nM) for Sec with a wide linear range (0-70 MUM).
      Moreover, this probe can be conveniently used to detect Sec in serum samples,
      living cells, and animals, indicating it holds great promise for biological
      applications.

PMID- 28504518
TI  - A Breakthrough Efficiency of 19.9% Obtained in Inverted Perovskite Solar Cells by
      Using an Efficient Trap State Passivator Cu(thiourea)I.
AB  - It is extremely significant to study the trap state passivation and minimize the
      trap states of perovskite to achieve high-performance perovskite solar cells
      (PSCs). Here, we have first revealed and demonstrated that a novel p-type
      conductor Cu(thiourea)I [Cu(Tu)I] incorporated in perovskite layer can
      effectively passivate the trap states of perovskite via interacting with the
      under-coordinated metal cations and halide anions at the perovskite crystal
      surface. The trap state energy level of perovskite can be shallowed from 0.35
      0.45 eV to 0.25-0.35 eV. In addition, the incorporated Cu(Tu)I can participate in
      constructing the p-i bulk heterojunctions with perovskite, leading to an increase
      of the depletion width from 126 to 265 nm, which is advantageous for accelerating
      hole transport and reducing charge carrier recombination. For these two
      synergistic effects, Cu(Tu)I can play a much better role than that of the
      traditional p-type conductor CuI, probably due to its identical valence band
      maximum with that of perovskite, which enables to not only lower the trap state
      energy level to a greater extent but also eliminate the potential wells for holes
      at the p-i heterojunctions. After optimization, a breakthrough efficiency of
      19.9% has been obtained in the inverted PSCs with Cu(Tu)I as the trap state
      passivator of perovskite.

PMID- 28504519
TI  - Longitudinal associations between adult children's relations with parents and
      intimate partners.
AB  - Drawing on 5 waves of multiple-informant data gathered from focal participants
      and their parents and intimate partners (n = 360 families) who completed annual
      surveys in the German Family Panel (pairfam) study, the present investigation
      examined bidirectional associations between the development of adults'
      conflictual and intimate interactions with their parents and intimate partners.
      Autoregressive cross-lagged latent change score modeling results revealed a
      robust pattern of coordinated development between parent-adult child and couple
      conflictual and intimate interactions: increases in conflict and intimacy in one
      relationship were contemporaneously intertwined with changes in the other
      relationship. Additionally, prior couple intimacy and conflict predicted future
      parent-adult child relations in 7 out of 14 cross-lagged pathways examined, but
      parent-adult child conflict and intimacy was only associated with future couple
      interactions in 1 pathway. These associations were not moderated by the gender of
      parents or the adult child or whether the adult child was a young adult or
      nearing midlife. Frequency of contact between parents and the adult child
      moderated some associations. Adults simultaneously juggle ties with parents and
      intimate partners, and this study provides strong evidence supporting the
      coordinated development of conflictual and intimate patterns of interaction in
      each relationship. (PsycINFO Database Record

PMID- 28504520
TI  - Prayer and forgiveness: Beyond relationship quality and extension to marriage.
AB  - The majority of the world population profess religious/spiritual beliefs and
      prayer is a form of spiritual activity common across numerous religious/spiritual
      belief systems. Three studies therefore examined the role of prayer in romantic
      relationships. Study 1 (n = 91) showed that prayer for a dating partner predicted
      lower aggressive tendencies and greater forgiveness of partner transgressions,
      independently of relationship closeness. Study 2 (n = 89 married couples) is
      among the first to examine the prayer-forgiveness association using dyadic data.
      Controlling for relationship satisfaction in the actor-partner interdependence
      model, prayer for the spouse predicted own forgiveness but not partner's reports
      of their own forgiveness. To obviate the problem of obtaining all the data from
      the same reporter, Study 3 (n = 91 married couples) used partner reports of the
      spouse's forgiveness in an actor-partner interdependence model analysis.
      Controlling for religiosity, the results showed that prayer for the partner
      predicted partner reports of the prayer's forgiveness. The implications of these
      results are then discussed. (PsycINFO Database Record

PMID- 28504522
TI  - The construct-behavior gap in behavioral decision research: A challenge beyond
      replicability.
AB  - Behavioral decision research compares theoretical constructs like preferences to
      behavior such as observed choices. Three fairly common links from constructs to
      behavior are (1) to tally, across participants and decision problems, the number
      of choices consistent with one predicted pattern of pairwise preferences; (2) to
      compare what most people choose in each decision problem against a predicted
      preference pattern; or (3) to enumerate the decision problems in which two
      experimental conditions generate a 1-sided significant difference in choice
      frequency 'consistent' with the theory. Although simple, these theoretical links
      are heuristics. They are subject to well-known reasoning fallacies, most notably
      the fallacy of sweeping generalization and the fallacy of composition. No amount
      of replication can alleviate these fallacies. On the contrary, reiterating
      logically inconsistent theoretical reasoning over and again across studies
      obfuscates science. As a case in point, we consider pairwise choices among simple
      lotteries and the hypotheses of overweighting or underweighting of small
      probabilities, as well as the description-experience gap. We discuss ways to
      avoid reasoning fallacies in bridging the conceptual gap between hypothetical
      constructs, such as, for example, "overweighting" to observable pairwise choice
      data. Although replication is invaluable, successful replication of hard-to
      interpret results is not. Behavioral decision research stands to gain much
      theoretical and empirical clarity by spelling out precise and formally explicit
      theories of how hypothetical constructs translate into observable behavior.
      (PsycINFO Database Record

PMID- 28504521
TI  - Family dinner frequency interacts with dinnertime context in associations with
      child and parent BMI outcomes.
AB  - For youth and parents, frequent family meals have been consistently associated
      with positive dietary outcomes but less consistently associated with lower body
      mass index (BMI). Researchers have speculated dinnertime context (dinnertime
      routines, parent dinnertime media use) may interact with family meal frequency to
      impact associations with BMI. The present study evaluates the associations and
      interactions between dinnertime context measures and family dinner frequency with
      parent and child BMI. This cross-sectional study uses baseline data from the
      Healthy Home Offerings via the Mealtime Environment (HOME) Plus randomized
      control trial that aimed to prevent childhood obesity. Participants (160 parent
      child dyads) completed psychosocial surveys and were measured for height and
      weight. General linear models tested associations and interactions between
      dinnertime context measures and family dinner frequency with parent and child
      BMI, adjusted for race and economic assistance. Lower parent dinnertime media use
      and higher dinnertime routines were significantly associated with lower child BMI
      z scores but not parent BMI scores. Interaction-moderation findings suggest
      higher family dinner frequency amplifies the healthful impact of the dinnertime
      context on child BMI z scores. Additionally, findings emphasize that promoting
      frequent family meals along with consistent routines and reduction in parent
      dinnertime media use may be important for the prevention of childhood obesity.
      (PsycINFO Database Record

PMID- 28504524
TI  - Healthy aging is associated with decreased risk-taking in motor decision-making.
AB  - Healthy aging is associated with changes in both cognitive abilities, including
      decision-making, and motor control. Previous research has shown that young
      healthy observers are close to optimal when they perform a motor equivalent of
      economic decision-making tasks that are known to produce suboptimal decision
      patterns. We tested both younger (age 20-29) and older (age 60-79) adults in such
      a task, which involved rapid manual aiming and monetary rewards and punishments
      contingent on hitting different areas on a touch screen. Older adults were as
      close to optimal as younger adults at the task, but differed from the younger
      adults in their strategy. Older adults appeared to be relatively less risk
      seeking, as evidenced by the fact that they adjusted their aiming strategy to a
      larger extent to avoid the penalty area. A model-based interpretation of the
      results suggested that the change in aiming strategy between younger and older
      adults was mainly driven by the fact that the first weighted monetary gains more
      than losses, rather than by a mis-estimation of one's motor variability. The
      results parallel the general finding that older adults tend to be less risk
      seeking than younger adults in economic decision-making and complement the
      observation that children are even more risk-seeking than younger adults in a
      similar motor decision-making paradigm. (PsycINFO Database Record

PMID- 28504523
TI  - Decomposition of a sensory prediction error signal for visuomotor adaptation.
AB  - To accomplish effective motor control, the brain contains an internal forward
      model that predicts the expected sensory consequence of a motor command. When
      this prediction is inaccurate, a sensory prediction error is produced which
      adapts the forward model to make more accurate predictions of future movements.
      Other types of errors, such as task performance errors or reward, play less of a
      role in adapting a forward model. This raises the following question: What unique
      information is conveyed by the sensory prediction error that results in forward
      model adaptation? sensory prediction errors typically contain both the magnitude
      and direction of the error, but it is unclear if both components are necessary
      for adaptation or a single component is sufficient. In this article, we address
      this by having participants learn to counter a visuomotor rotation, which induces
      an angular mismatch between movements of the hand and visual feedback. We
      manipulated the information content of the visual feedback, in the form of a
      line, which accurately represented only the magnitude (distance), direction, or
      both magnitude and direction, of the virtual cursor relative to the target. We
      demonstrate that sensorimotor adaptation does not occur, or is minimal, when
      feedback is limited to information about the magnitude of an error. In contrast,
      sensorimotor adaptation is present when feedback is limited only to the direction
      of an error or when it contains combined direction and magnitude information.
      This result stands in contrast to current computational models of cerebellar
      based sensorimotor adaptation that use error magnitude to drive adaptation.
      (PsycINFO Database Record

PMID- 28504525
TI  - Introspection of subjective feelings is sensitive and specific.
AB  - Conversely to behaviorist ideas, recent studies suggest that introspection can be
      accurate and reliable. However, an unresolved question is whether people are able
      to report specific aspects of their phenomenal experience, or whether they report
      more general nonspecific experiences. To address this question, we investigated
      the sensitivity and validity of our introspection for different types of
      conflict. Taking advantage of the congruency sequence effect, we dissociated
      response conflict while keeping visual conflict unchanged in a Stroop and in a
      priming task. Participants were subsequently asked to report on either their
      experience of urge to err or on their feeling of visual conflict. Depending on
      the focus of the introspection, subjective reports specifically followed either
      the response conflict or the visual conflict. These results demonstrate that our
      introspective reports can be sensitive and that we are able to dissociate
      specific aspects of our phenomenal experiences in a valid manner. (PsycINFO
      Database Record

PMID- 28504526
TI  - Endogenous formation of preferences: Choices systematically change willingness-to
      pay for goods.
AB  - Standard decision theory assumes that choices result from stable preferences.
      This position has been challenged by claims that the act of choosing between
      goods may alter preferences. To test this claim, we investigated in three
      experiments whether choices between equally valued snack food items can
      systematically shape preferences. We directly assessed changes in participants'
      willingness-to-pay for these items, some of which could be bought at an auction
      after the experiment, while others could not. We found that chosen items were
      valued higher, and nonchosen items were valued lower; yet this postdecisional
      refinement of preferences was only observed for choices and valuations that were
      relevant, that is, incentive-compatible for items that were available for
      consumption. Supplementary analyses revealed that incentive-incompatible
      elicitations of preferences were unreliable and may have masked potential effects
      of choices on preferences. In conclusion, we propose that preferences can change
      endogenously, that is, in the absence of external feedback or information, but
      rather as a function of previous relevant choices. (PsycINFO Database Record

PMID- 28504527
TI  - The testing effect under divided attention.
AB  - Memory retrieval often enhances later memory compared with restudying (i.e., the
      testing effect), indicating that retrieval does not simply reveal but also
      modifies memory representations. Dividing attention (DA) during encoding greatly
      disrupts later memory performance while DA during retrieval typically has modest
      effects-but what of the memory-modifying effects of retrieval? If these effects
      are similar to study-based encoding, they should be greatly disrupted by DA, a
      possibility consistent with elaborative and effortful accounts of the testing
      effect. Alternatively, the mnemonic consequences of retrieval may be largely
      resilient to distraction, like retrieval itself. In 3 experiments, participants
      studied word pairs (Phase 1) then engaged in restudy of some pairs and retrieval
      of others (Phase 2), followed by a final cued-recall test (Phase 3). Phase 2
      restudy and retrieval occurred under full attention (FA) or DA. The experiments
      were designed to induce either material-specific (Experiments 1 and 2) or
      material-general (Experiment 3) interference, as well as to produce comparable
      secondary task performance between the restudy and retrieval groups (Experiments
      2 and 3). Consistent with prior research, retrieval improved final recall (i.e.,
      the testing effect) whereas DA disrupted final recall. Critically, the 2 factors
      interacted such that the negative effect of DA on final recall was substantial in
      the restudy condition but quite modest in the retrieval condition-resulting in a
      larger testing effect in the DA than FA condition. The encoding effects of
      retrieval seem resilient to distraction which has implications for theories of
      the testing effect. (PsycINFO Database Record

PMID- 28504528
TI  - The importance of arousal for variation in working memory capacity and attention
      control: A latent variable pupillometry study.
AB  - A great deal of prior research has examined the relation between working memory
      capacity (WMC) and attention control. The current study explored the role of
      arousal in individual differences in WMC and attention control. Participants
      performed multiple WMC and attention control tasks. During the attention control
      tasks participants were periodically probed regarding their current attentional
      state and both baseline and task-evoked pupillary responses were recorded as
      indicators of tonic arousal and phasic arousal because of attentional effort,
      respectively. Latent variable analyses demonstrated that variability in both
      baseline pupil diameter and task-evoked responses was related to WMC, attention
      control, and off-task thinking. Furthermore, structural equation models suggested
      that variability in both baseline pupil diameter and task-evoked pupillary
      responses predicted off-task thinking, which in turn predicted variation in WMC
      and attention control. These results provide important evidence linking moment-to
      moment fluctuations in arousal to individual differences in WMC and attention
      control. (PsycINFO Database Record

PMID- 28504529
TI  - The cause of category-based distortions in spatial memory: A distribution
      analysis.
AB  - Recall of remembered locations reliably reflects a compromise between a target's
      true position and its region's prototypical position. The effect is quite robust,
      and a standard interpretation for these data is that the metric and categorical
      codings blend in a Bayesian combinatory fashion. However, there has been no
      direct experimental evidence that the 2 codings are actually combined. That is,
      at least 2 mechanisms can produce biased mean responses: (a) people may in fact
      take a weighted average of the metric and categorical representations, but (b)
      these 2 codings may instead compete for response, each winning with a certain
      probability. The present work investigated these 2 hypotheses for the cause of
      category-based distortions using a new distribution analysis. Participants viewed
      a target within a blank circle and reproduced its location after a short delay.
      The error data for individual participants were fit with a kernel curve, which
      provides a distribution without the assumption of normality. Almost all
      individual distributions displayed a clear biased main peak, indicating a
      weighted average between the representations, not an alteration between the 2
      representations. (PsycINFO Database Record

PMID- 28504530
TI  - Framing affects scale usage for judgments of learning, not confidence in memory.
AB  - Framing metacognitive judgments of learning (JOLs) in terms of the likelihood of
      forgetting rather than remembering consistently yields a counterintuitive
      outcome: The mean of participants' forget-framed JOLs is often higher (after
      reverse-scoring) than the mean of their remember-framed JOLs, suggesting greater
      confidence in memory. In the present experiments, we tested 2 competing
      explanations for this pattern of results. The optimistic-anchoring hypothesis
      suggests that forget-framed JOLs are associated with greater optimism about
      memory than are remember-framed JOLs, which leads to their greater magnitude. The
      differential-scaling hypothesis suggests that forget-framed JOLs and remember
      framed JOLs will often be distributed differently across the JOL scale, resulting
      in means that also often differ. Participants in 3 experiments studied simple
      memory materials and made JOLs predicting their memory performance for those
      items. They made their JOLs in terms of either the likelihood of remembering or
      forgetting. In contrast to the optimistic-anchoring hypothesis, the mean of
      participants' forget-framed JOLs was unaffected by information concerning the
      supposed difficulty of the task (Experiment 1), was lower than for remember
      framed JOLs in a task selected to evoke high JOLs (Experiment 2), and
      demonstrated equivalent confidence in memory when participants were restricted to
      a yes-no binary response (Experiment 3). In support of the differential-scaling
      hypothesis, participants' forget-framed JOLs were consistently symmetrically
      distributed across the JOL scale, resulting in a mean at the center of the
      judgment scale that was often higher than that for remember-framed JOLs. Framing
      therefore affects how participants scale their JOLs, not their confidence in
      their memory. (PsycINFO Database Record

PMID- 28504531
TI  - The role of familiarity in correcting inaccurate information.
AB  - People frequently continue to use inaccurate information in their reasoning even
      after a credible retraction has been presented. This phenomenon is often referred
      to as the continued influence effect of misinformation. The repetition of the
      original misconception within a retraction could contribute to this phenomenon,
      as it could inadvertently make the "myth" more familiar-and familiar information
      is more likely to be accepted as true. From a dual-process perspective,
      familiarity-based acceptance of myths is most likely to occur in the absence of
      strategic memory processes. Thus, we examined factors known to affect whether
      strategic memory processes can be utilized: age, detail, and time. Participants
      rated their belief in various statements of unclear veracity, and facts were
      subsequently affirmed and myths were retracted. Participants then rerated their
      belief either immediately or after a delay. We compared groups of young and older
      participants, and we manipulated the amount of detail presented in the
      affirmative or corrective explanations, as well as the retention interval between
      encoding and a retrieval attempt. We found that (a) older adults over the age of
      65 were worse at sustaining their postcorrection belief that myths were
      inaccurate, (b) a greater level of explanatory detail promoted more sustained
      belief change, and (c) fact affirmations promoted more sustained belief change in
      comparison with myth retractions over the course of 1 week (but not over 3
      weeks), This supports the notion that familiarity is indeed a driver of continued
      influence effects. (PsycINFO Database Record

PMID- 28504532
TI  - Orthography affects second language speech: Double letters and geminate
      production in English.
AB  - Second languages (L2s) are often learned through spoken and written input, and L2
      orthographic forms (spellings) can lead to non-native-like pronunciation. The
      present study investigated whether orthography can lead experienced learners of
      EnglishL2 to make a phonological contrast in their speech production that does
      not exist in English. Double consonants represent geminate (long) consonants in
      Italian but not in English. In Experiment 1, native English speakers and
      EnglishL2 speakers (Italians) were asked to read aloud English words spelled with
      a single or double target consonant letter, and consonant duration was compared.
      The EnglishL2 speakers produced the same consonant as shorter when it was spelled
      with a single letter, and longer when spelled with a double letter. Spelling did
      not affect consonant duration in native English speakers. In Experiment 2,
      effects of orthographic input were investigated by comparing 2 groups of
      EnglishL2 speakers (Italians) performing a delayed word repetition task with or
      without orthographic input; the same orthographic effects were found in both
      groups. These results provide arguably the first evidence that L2 orthographic
      forms can lead experienced L2 speakers to make a contrast in their L2 production
      that does not exist in the language. The effect arises because L2 speakers are
      affected by the interaction between the L2 orthographic form (number of letters),
      and their native orthography-phonology mappings, whereby double consonant letters
      represent geminate consonants. These results have important implications for
      future studies investigating the effects of orthography on native phonology and
      for L2 phonological development models. (PsycINFO Database Record

PMID- 28504533
TI  - Cue integration in spatial search for jointly learned landmarks but not for
      separately learned landmarks.
AB  - The authors investigated how humans use multiple landmarks to locate a goal.
      Participants searched for a hidden goal location along a line between 2 distinct
      landmarks on a computer screen. On baseline trials, the location of the landmarks
      and goal varied, but the distance between each of the landmarks and the goal was
      held constant, with 1 landmark always closer to the goal. In Experiment 1, some
      baseline trials provided both landmarks, and some provided only 1 landmark. On
      probe trials, both landmarks were shifted apart relative to the previously
      learned goal location. Participants searched between the locations specified by
      the 2 landmarks and their search locations were shifted more toward the nearer
      landmark, suggesting a weighted integration of the conflicting landmarks.
      Moreover, the observed variance in search responses when both cues were presented
      in their normal locations was reduced compared to the variance on tests with
      single landmarks. However, the variance reduction and the weightings of the
      landmarks did not always show Bayesian optimality. In Experiment 2, some
      participants were trained only with each of the single landmarks. On subsequent
      tests with the 2 cues in conflict, searching did not shift toward the nearer
      landmark and the variance of search responses of these single-cue trained
      participants was larger than their variance on single-landmark tests, and even
      larger than the variance predicted by using the 2 landmarks alternatively on
      different trials. Taken together, these results indicate that cue combination
      occurs only when the landmarks are presented together during the initial learning
      experience. (PsycINFO Database Record

PMID- 28504534
TI  - Food for happy thought: Glucose protects age-related positivity effects under
      cognitive load.
AB  - Older adults show a preference for positive information, which disappears under
      high task demands. We examined whether glucose can help older adults preserve
      their positivity effect (PE) under high cognitive load. One hundred twenty-two
      adults (40 young and 42 older in Experiment 1; 40 older in Experiment 2) consumed
      a glucose (25 g) or a taste-matched placebo drink and completed an immediate
      recall task of emotional word-lists presented under high- and low-load
      conditions. Older adults showed PEs for low-load lists. Whereas PEs disappeared
      for older-placebo participants for high-load lists, older-glucose participants
      retained their positive preference. Providing the brain with extra energy
      resources can help older adults achieve PEs even under demanding conditions.
      (PsycINFO Database Record

PMID- 28504535
TI  - Route repetition and route reversal: Effects of age and encoding method.
AB  - Previous research indicates age-related impairments in learning routes from a
      start location to a target destination. There is less research on age effects on
      the ability to reverse a learned path. The method used to learn routes may also
      influence performance. This study examined how encoding methods influence the
      ability of younger and older adults to recreate a route in a virtual reality
      environment in forward and reverse directions. Younger (n = 50) and older (n =
      50) adults learned a route either by self-navigation through the virtual
      environment or through studying a map. At test, participants recreated the route
      in the forward and reverse directions. Older adults in the map study condition
      had greater difficulty learning the route in the forward direction compared to
      younger adults. Older adults who learned the route by self-navigation were less
      accurate in traversing the route in the reverse compared to forward direction
      after a delay. In contrast, for older adults who learned via map study there were
      no significant differences between forward and reverse directions. Results
      suggest that older adults may not as readily develop and retain a sufficiently
      flexible representation of the environment during self-navigation to support
      accurate route reversal. Thus, initially learning a route from a map may be more
      difficult for older adults, but may ultimately be beneficial in terms of better
      supporting the ability to return to a start location. (PsycINFO Database Record

PMID- 28504536
TI  - A signal-detection analysis of eyewitness identification across the adult
      lifespan.
AB  - Middle-aged and older adults are frequently victims and witnesses of crime, but
      knowledge of how identification performance changes over the adult life span is
      sparse. The authors asked young (18-30 years), middle-aged (31-59 years), and
      older (60-95 years) adults (N = 2,670) to watch a video of a mock crime and to
      attempt to identify the culprit from a fair lineup (in which all of the lineup
      members matched the appearance of the suspect) or an unfair lineup (in which the
      suspect stood out). They also asked subjects to provide confidence ratings for
      their identification decisions. To examine identification performance, the
      authors used a standard response-type analysis, receiver operating characteristic
      analysis, and signal-detection process modeling. The results revealed that, in
      fair lineups, aging was associated with a genuine decline in recognition ability
      discriminability-and not an increased willingness to choose. Perhaps most
      strikingly, middle-aged and older adults were generally effective at regulating
      their confidence judgments to reflect the likely accuracy of their suspect
      identification decisions. Model-fitting confirmed that the older adults spread
      their decision criteria such that identifications made with high confidence were
      likely to be highly accurate, despite the substantial decline in discriminability
      with age. In unfair lineups, ability to discriminate between innocent and guilty
      suspects was poor in all age groups. The research enhances theoretical
      understanding of the ways in which identification behavior changes with age, and
      has important practical implications for how legal decision-makers should
      interpret identifications made by middle-aged and older eyewitnesses. (PsycINFO
      Database Record

PMID- 28504537
TI  - A tale of two measures: Concordance between the ARSMA-II and the BIQ
      acculturation scales among Latino immigrant families.
AB  - Acculturation refers to the extent to which an individual immigrant (or immigrant
      group) acquires the customs and characteristics of a new receiving society and/or
      retains the customs and characteristics of the person's or group's cultural
      heritage. Different acculturation measures are often assumed to be
      interchangeable, although this assumption is rarely tested empirically. The
      purpose of the present study was to examine the overlap between 2 commonly used
      measures of acculturation among individuals of Latino/Hispanic ancestry in the
      United States, the Acculturation Rating Scale for Mexican Americans II (ARSMA-II)
      and the Bicultural Involvement Questionnaire-Short Version (BIQ-S). Specifically,
      we examined the ways in which scores from the 2 measures relate to one another,
      as well as similarities versus differences in the ways they predict external
      variables of interest (e.g., family functioning, parenting, and youth adjustment)
      that acculturation is known to influence. Findings indicate distinct patterns of
      results for the 2 measures. For instance, though the BIQ-S focuses entirely on
      language use and other cultural practices, the ARSMA-II more consistently relates
      to language variables. Further, adolescent BIQ-S cultural heritage scores related
      negatively to risks for and engagement in alcohol use-supporting prior findings
      whereas ARSMA-II scores were unrelated to alcohol use. Given the largely
      nonoverlapping set of relationships of the BIQ-S and the ARSMA-II subscale scores
      with measures of language dominance and conflict, measures of parenting, and
      measures of youth outcomes, we recommend that studies utilize both of these
      measures to fully appraise acculturation in this population. (PsycINFO Database
      Record

PMID- 28504538
TI  - Self-efficacy for coping with cancer: Revision of the Cancer Behavior Inventory
      (Version 3.0).
AB  - Based on self-regulation and self-efficacy theories, the Cancer Behavior
      Inventory (CBI; Heitzmann et al., 2011; Merluzzi & Martinez Sanchez, 1997;
      Merluzzi, Nairn, Hegde, Martinez Sanchez, & Dunn, 2001) was developed as a
      measure of self-efficacy strategies for coping with cancer. In the latest
      revision, CBI-V3.0, a number of psychometric and empirical advances were made:
      (a) the reading level was reduced to 6th-grade level; (b) individual interviews
      and focus groups were used to revise items; (c) a new spiritual coping subscale
      was added; (d) data were collected from 4 samples (total N = 1,405) to conduct an
      exploratory factor analysis with targeted rotation, 2 confirmatory factor
      analyses, and differential item functioning; (e) item trimming was used to reduce
      the total number to 27; (f) internal consistency and test-retest reliability were
      computed; and (g) extensive validity testing was conducted. The results, which
      build upon the strengths of prior versions, confirm a structurally and
      psychometrically sound and unbiased measure of self-efficacy strategies for
      coping with cancer with a reduced number of items for ease of administration. The
      factors include Maintaining Activity and Independence, Seeking and Understanding
      Medical Information, Emotion Regulation, Coping With Treatment Related Side
      Effects, Accepting Cancer/Maintaining a Positive Attitude, Seeking Social
      Support, and Using Spiritual Coping. Internal consistency (alpha = .946), test
      retest reliability (r = .890; 4 months), and validity coefficients with a variety
      of relevant measures indicated strong psychometric properties. The new 27-item
      CBI-V3.0 has both research utility and clinical utility as a screening and
      treatment-planning measure of self-efficacy strategies for coping with cancer.
      (PsycINFO Database Record

PMID- 28504539
TI  - Identification of questionable data using validity indices and item response
      theory methods: Examinations with a teacher-rating scale.
AB  - To assess quality, psychological instruments often include additional scales or
      validity indices to alert users to the presence of questionable data. Although
      identified cases are often scrutinized further or removed, it is not fully
      understood how such cases may affect overall analyses if retained. Using a
      teacher-report instrument of child behavior, this study examined 5 different
      validity indices: F-Index, Consistency Index, Response Pattern Index, Rasch
      Outfit, and Rasch Infit. Results showed that methods largely did not identify
      similar cases. Removing flagged cases did not have a great effect on reliability
      estimates or validity coefficients. Hierarchical linear modeling illustrated that
      differences in validity indices were significantly related to years of teaching
      experience and level of education for the F-Index. In general, before using
      social-emotional screeners, teacher training may be useful to help minimize
      response effects. (PsycINFO Database Record

PMID- 28504540
TI  - Meta-analysis of cognitive-behavioral treatments for adult ADHD.
AB  - OBJECTIVE: We conducted a meta-analysis of cognitive-behavioral treatment (CBT)
      studies for adult attention-deficit/hyperactivity disorder (ADHD), examining
      effects versus control and effects pre-to-post treatment to maximize the clinical
      and research utility of findings from this growing literature. METHOD: Eligible
      studies tested adults meeting criteria for Diagnostic and Statistical Manual of
      Mental Disorders ADHD as determined by interview or using a standardized rating
      scale and measured ADHD symptoms or related impairment at baseline and
      posttreatment. We analyzed data from 32 studies from published and unpublished
      sources available through December 2015. Effect size calculations included up to
      896 participants. RESULTS: Using a random effects model, we found that CBTs had
      medium-to-large effects from pre- to posttreatment (self-reported ADHD symptoms:
      g = 1.00; 95% confidence interval [CI: 0.84, 1.16]; self-reported functioning g =
      .73; 95% CI [0.46, 1.00]) and small-to-medium effects versus control (g = .65;
      95% CI [0.44, 0.86] for symptoms, .51; 95% CI [0.23, 0.79] for functioning).
      Effect sizes were heterogeneous for most outcome measures. Studies with active
      control groups showed smaller effect sizes. Neither participant medication status
      nor treatment format moderated pre-to-post treatment effects, and longer
      treatments were not associated with better outcomes. CONCLUSIONS: Current CBTs
      for adult ADHD show comparable effect sizes to behavioral treatments for children
      with ADHD, which are considered well-established treatments. Future treatment
      development could focus on identifying empirically supported principles of
      treatment-related change for adults with ADHD. We encourage researchers to report
      future findings in a way that is amenable to meta-analytic review. (PsycINFO
      Database Record

PMID- 28504541
TI  - Interpersonal pathoplasticity and trajectories of change in routine adolescent
      and young adult residential substance abuse treatment.
AB  - BACKGROUND: Partnerships between mental health care stakeholders provide a
      context for generalizable clinical research with implications for quality
      improvement. In the context of a partnership between an adolescent residential
      substance abuse disorder (SUD) treatment center and clinical researchers,
      stakeholders identified knowledge gaps (internal and the field broadly) with
      regard to patient interpersonal factors that influence working alliance and acute
      SUD residential treatment outcome trajectories. OBJECTIVE: To (a) examine
      interpersonal pathoplasticity and identify interpersonal subtypes in a
      naturalistic sample of adolescent and young-adult patients presenting for routine
      residential SUD treatment and (b) investigate the association between identified
      interpersonal subtypes and working alliance and acute treatment outcome
      trajectories. METHOD: N = 100 patients (Mage = 17.39 years, 68% male, 84% White)
      completed self-reports of symptom and functioning outcomes, interpersonal
      problems, and the working alliance on multiple occasions between admission and
      discharge. Multiple methods were used to identify interpersonal subtypes and test
      pathoplasticity. Interpersonal subtype was entered as a predictor in respective
      multilevel models of working alliance and symptom outcome. RESULTS: Interpersonal
      subtypes of vindictive and exploitable patients demonstrated pathoplasticity.
      Subtype did not predict working alliance trajectories; however, a significant
      interaction between interpersonal subtype and a quadratic effect for time
      demonstrated that exploitable patients with longer than average treatment lengths
      experienced attenuated symptom change over the course of treatment whereas
      vindictive patients appeared to demonstrate steady progress. CONCLUSIONS:
      Interpersonal assessments should be integrated into residential SUD treatment to
      identify patients with an exploitable interpersonal style who might require
      additional attention or alternative interventions. (PsycINFO Database Record

PMID- 28504543
TI  - Clear Cell Renal Cell Carcinoma: Identifying the Loss of the Y Chromosome on
      Multiphasic MDCT.
AB  - OBJECTIVE: The objective of our study was to investigate whether multiphasic MDCT
      enhancement can help identify clear cell renal cell carcinomas (RCCs) with the
      loss of the Y chromosome. MATERIALS AND METHODS: We derived a cohort of 43 clear
      cell RCCs in men who underwent preoperative four-phase renal mass MDCT from
      October 2000 to August 2013. Each lesion was segmented in its entirety on axial
      images. A computer-assisted detection algorithm selected a 0.5-cm-diameter region
      of maximal attenuation within each lesion in each phase. A 0.5-cm-diameter ROI
      was manually placed on uninvolved renal cortex in each phase. The relative
      attenuation of each lesion was calculated as follows: [(maximal lesion
      attenuation - cortex attenuation) / cortex attenuation] * 100. Absolute
      attenuation and relative attenuation in each phase were compared using t tests.
      RESULTS: Both clear cell RCCs with the loss of the Y chromosome and clear cell
      RCCs without the loss of the Y chromosome exhibited peak enhancement in the
      corticomedullary phase. However, relative nephrographic attenuation of clear cell
      RCCs with the loss of Y was significantly less than that of clear cell RCCs
      without the loss of Y (mean, -8.9 vs 8.4 respectively; p = 0.013). A relative
      nephrographic attenuation threshold of -1.6 identified the loss of Y with an
      accuracy of 70% (30/43), sensitivity of 73% (16/22), and specificity of 67%
      (14/21). CONCLUSION: Multiphasic MDCT enhancement may assist in identifying the
      loss of the Y chromosome in clear cell RCCs; this result should be validated in a
      large prospective trial.

PMID- 28504545
TI  - Detection of Hemodynamically Significant Coronary Artery Stenosis With CT
      Enhancement Ratio: A Validation Study in a Porcine Model.
AB  - OBJECTIVE: Although numerous techniques that are based on CT number analysis have
      been proposed, the assessment of hemodynamically significant coronary artery
      stenosis remains a great challenge. The purpose of this study is to validate use
      of the CT enhancement ratio in the detection of hemodynamically significant
      coronary artery stenosis in a porcine model. MATERIALS AND METHODS: Experiments
      involving eight closed-chest swine were performed. A balloon catheter was placed
      into the left anterior descending coronary artery to simulate different degrees
      of luminal stenosis. The myocardial blood flow (MBF) ratio was measured using the
      colored microsphere technique. The fractional flow reserve was measured using an
      invasive pressure wire. CT scans were performed during the first-pass phase,
      while the pigs were undergoing adenosine stress tests. The CT enhancement ratio
      and the CT attenuation ratio were calculated using data from the CT images
      obtained. RESULTS: Results suggested that the CT enhancement ratio had a strong
      correlation (y = 0.07245 + 0.09963x; r2 = 0.898; p < 0.001) with the MBF ratio
      measured using the microsphere technique, whereas only moderate correlation (y = 
      1.5508 + 2.2684x; r2 = 0.498; p < 0.001) was noted between the CT attenuation
      ratio and the MBF ratio measured using the microsphere technique. In ROC curve
      analysis, the AUC values of the CT enhancement ratio and the CT attenuation ratio
      were 0.927 and 0.829, respectively, with regard to the detection of significant
      ischemia during adenosine stress tests, as defined by the fractional flow
      reserve. CONCLUSION: The CT enhancement ratio provides a reliable prediction of
      the MBF ratio measured using the microsphere technique, indicating that this
      metric has good diagnostic performance in the detection of hemodynamically
      significant coronary artery stenosis. The CT enhancement ratio may have potential
      for use as an imaging biomarker for the relative quantitative assessment of
      myocardial perfusion.

PMID- 28504542
TI  - Do changes in trauma-related beliefs predict PTSD symptom improvement in
      prolonged exposure and sertraline?
AB  - OBJECTIVE: Negative trauma-related belief change has been found to predict
      subsequent improvement in symptoms of posttraumatic stress disorder (PTSD) in
      prolonged exposure (PE) and other therapies, consistent with several
      psychological theories of treatment change (e.g., Foa & Kozak, 1986). However,
      belief change has not been examined in selective serotonin reuptake inhibitors
      such as sertraline. We examined processes associated with symptom improvement in
      2 treatments for PTSD, hypothesizing that belief change would robustly predict
      PTSD improvement in patients treated with PE but not those treated with
      sertraline, reflecting moderation by treatment. METHOD: Patients with chronic
      PTSD (N = 134; 78% women, 71.6% Caucasian, M = 38.1 years, SD = 11.8) received 10
      weeks of PE or sertraline in a randomized, controlled trial. Patients reported
      PTSD and depression symptoms, and trauma-related beliefs (Post-Traumatic
      Cognitions Inventory; Foa, Ehlers, Clark, D Tolin, & Orsillo, 1999) at
      pretreatment, every treatment session, and posttreatment. RESULTS: Using time
      lagged mixed regression models, change in trauma-related beliefs predicted
      subsequent PTSD symptom improvement, an effect moderated by treatment and
      particularly strong in PE (d = 0.93) compared with sertraline (d = 0.35). Belief
      change also predicted depressive symptom improvement but more modestly and
      bidirectionally, with no difference by treatment modality. CONCLUSIONS: Trauma
      related belief change precedes PTSD improvement more robustly in PE than in
      sertraline and with greater specificity compared with depressive symptoms. These
      findings highlight potentially divergent processes contributing to symptom change
      in these PTSD treatments, with belief change as a key mechanism of PE. (PsycINFO
      Database Record

PMID- 28504546
TI  - Use of a 3D-Printed Abdominal Compression Device to Facilitate CT Fluoroscopy
      Guided Percutaneous Interventions.
AB  - OBJECTIVE: The purpose of this article is to describe a handheld external
      compression device used to facilitate CT fluoroscopy-guided percutaneous
      interventions in the abdomen. CONCLUSION: The device was designed with computer
      aided design software to modify an existing gastrointestinal fluoroscopy
      compression device and was constructed by 3D printing. This abdominal compression
      device facilitates access to interventional targets, and its use minimizes
      radiation exposure of radiologists. Twenty-one procedures, including biopsies,
      drainage procedures, and an ablation, were performed with the device. Radiation
      dosimetry data were collected during two procedures.

PMID- 28504544
TI  - Radial Ultrashort TE Imaging Removes the Need for Breath-Holding in Hepatic Iron
      Overload Quantification by R2* MRI.
AB  - OBJECTIVE: The objective of this study is to evaluate radial free-breathing (FB)
      multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho
      gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron
      content (HIC) in sedated patients and subjects unable to perform breath-hold (BH)
      maneuvers. MATERIALS AND METHODS: FB multiecho GRE imaging and FB multiecho UTE
      imaging were conducted for 46 test group patients with iron overload who could
      not complete BH maneuvers (38 patients were sedated, and eight were not sedated)
      and 16 control patients who could complete BH maneuvers. Control patients also
      underwent standard BH multiecho GRE imaging. Quantitative R2* maps were
      calculated, and mean liver R2* values and coefficients of variation (CVs) for
      different acquisitions and patient groups were compared using statistical
      analysis. RESULTS: FB multiecho GRE images displayed motion artifacts and
      significantly lower R2* values, compared with standard BH multiecho GRE images
      and FB multiecho UTE images in the control cohort and FB multiecho UTE images in
      the test cohort. In contrast, FB multiecho UTE images produced artifact-free R2*
      maps, and mean R2* values were not significantly different from those measured by
      BH multiecho GRE imaging. Motion artifacts on FB multiecho GRE images resulted in
      an R2* CV that was approximately twofold higher than the R2* CV from BH multiecho
      GRE imaging and FB multiecho UTE imaging. The R2* CV was relatively constant over
      the range of R2* values for FB multiecho UTE, but it increased with increases in
      R2* for FB multiecho GRE imaging, reflecting that motion artifacts had a stronger
      impact on R2* estimation with increasing iron burden. CONCLUSION: FB multiecho
      UTE imaging was less motion sensitive because of radial sampling, produced
      excellent image quality, and yielded accurate R2* estimates within the same
      acquisition time used for multiaveraged FB multiecho GRE imaging. Thus, FB
      multiecho UTE imaging is a viable alternative for accurate HIC assessment in
      sedated children and patients who cannot complete BH maneuvers.

PMID- 28504547
TI  - Site-Specific Onset of Low Bone Density and Correlation of Bone Turnover Markers
      in Exclusive Breastfeeding Mothers.
AB  - PURPOSE: Lactation often affects calcium metabolism and induces bone loss.
      Calcium supplementation and a high calcium diet are recommended to prevent bone
      loss, especially during inadequate calcium intake. Our study aimed at determining
      bone loss in breastfeeding mothers, and if it occurred, whether it was site
      specific and there were correlations between serum bone turnover markers.
      MATERIALS AND METHODS: Since the 6-month exclusive breastfeeding is usually
      recommended in several countries, our study examined bone mineral density (BMD)
      in early (1-2 month), mid (3-4 month)-, and late (5-6 month) lactation compared
      with nonpregnant, nonlactating control women. Site-specific bone loss was
      monitored in lumbar vertebrae and femora. Bone turnover markers, that is, C
      terminal telopeptide of type 1 collagen and N-terminal propeptide of type 1
      collagen (P1NP), were determined by electrochemiluminescence immunoassays.
      RESULTS: The onset of bone loss in exclusive breastfeeding mothers was site
      specific, for example, in the lumbar bone at mid-lactation and in the femoral
      bone in late lactation. Serum ionized calcium levels in late lactation were lower
      than the normal levels. In addition, a correlation was found between bone
      turnover marker, P1NP, and femoral BMD. CONCLUSIONS: The onset of bone loss in
      exclusive breastfeeding mothers was site specific, and the lumbar bone was a
      vulnerable and perhaps better representative site for bone loss detection. It was
      suggested that the optimal starting time for calcium supplementation should be
      before the mid-lactation when the bone loss was observed. In addition, the
      biochemical marker that best predicted the onset of bone loss in lactating women
      was P1NP.

PMID- 28504548
TI  - The Lumbar Neural Foramen and Transforaminal Epidural Steroid Injections: An
      Anatomic Review With Key Safety Considerations in Planning the Percutaneous
      Approach.
AB  - OBJECTIVE: The purpose of this article is to review the anatomy of the lumbar
      neural foramen and to describe techniques of transforaminal epidural steroid
      injections with emphasis on safety. Rare cases of paraplegia have been reported.
      CONCLUSION: Although no consensus currently exists about which approach is the
      safest, knowledge of the foraminal anatomy is a key consideration when choosing a
      needle approach for transforaminal epidural steroid injections.

PMID- 28504549
TI  - Determination of naloxegol in human biological matrices.
AB  - AIM: Naloxegol is an oral peripherally acting MU-opioid receptor antagonist
      approved for the treatment of opioid-induced constipation. Sensitive, robust,
      bioanalytical methods were required to quantitate naloxegol in human biological
      matrices as part of the clinical development program. METHODOLOGY/RESULTS:
      Analytical plasma samples were prepared using Solid Phase Extraction (SPE)
      coupled with concentration. The method's linearity was established at 0.1-50
      ng/ml with up to 100-fold dilution. Urine samples were analyzed directly
      postdilution; dialysate samples were extracted by supported liquid extraction.
      Sensitive liquid chromatography/mass spectrometry (LC-MS/MS) assays were
      developed and validated, and demonstrated acceptable precision, accuracy and
      selectivity for naloxegol in the appropriate matrices. CONCLUSION: Methods for
      quantifying naloxegol in human biological matrices have been successfully
      validated.

PMID- 28504551
TI  - Memorial-Wilma C. Diner.

PMID- 28504550
TI  - Liver Abscesses: Factors That Influence Outcome of Percutaneous Drainage.
AB  - OBJECTIVE: The purpose of this study was to identify the details of percutaneous
      catheter drainage (PCD) of pyogenic liver abscesses, the etiologic factors, and
      the management techniques that contribute to successful treatment. MATERIALS AND
      METHODS: The records of 75 consecutively registered patients who underwent PCD of
      96 abscesses at a single institution between May 2009 and May 2014 were
      retrospectively reviewed. Thirty-nine patients (52%) were oncology patients, and
      36 (48%) had recently undergone abdominal surgery. Primary success was defined as
      abscess healing with the primary PCD intervention and 30-day postdrainage
      survival. Salvage success was defined as abscess healing with follow-up secondary
      PCD placement for symptomatic hepatic satellite collections or for clinical
      recurrence. Catheter adjustments were performed during follow-up to optimize
      existing drains. Univariate, multivariate, and general linear mixed model
      analyses were performed. The median follow-up time after catheter removal was 6
      months (range, 2-62 months). RESULTS: Drains were primarily successful in 54
      patients (72%), and 17 patients (23%) needed salvage PCD; thus, overall success
      was achieved in 71 patients (95%). The other four patients (5%) died of sepsis.
      The primary success rate was reduced in patients with unresectable malignancies
      (p = 0.01), multiple abscesses (p = 0.01), and output >= 15 mL/d at catheter
      endpoint (n = 7, p = 0.001). Only unresectable malignancies had slightly lower
      overall success. Large abscesses (> 150 cm3) required more catheter adjustments
      and longer drainage duration to reach abscess cavity closure. Successfully
      drained abscesses reached cavity closure a mean of 23 days (95% CI, 20-27 days)
      after treatment. CONCLUSION: PCD was effective first-line treatment of
      complicated pyogenic liver abscesses, which often require catheter adjustment and
      salvage drainage procedures to reliably achieve success.

PMID- 28504552
TI  - Validation of electrochemiluminescence assays for highly sensitive and
      reproducible quantification of alpha-synuclein in cerebrospinal fluid.
AB  - AIM: alpha-Synuclein (aSyn), a putative cerebrospinal fluid biomarker, may
      support the diagnosis of neurodegenerative diseases. Previous studies led to
      conflicting results due to different preanalytical and analytical procedures.
      Standardized assays are required to allow for comparison of results from
      different laboratories. MATERIALS & METHODS: We performed a side-by-side
      validation of a commercially available (MSD, MD, USA) and a 'homebrew' assay for
      quantification of aSyn according to published guidelines. RESULTS: The data
      showed high sensitivity and reproducibility for both assays. Preanalytical and
      analytical parameters did not affect the outcome of measurements. CONCLUSION: We
      conclude that both assays are very close in performance and suitable for research
      application of cerebrospinal fluid aSyn.

PMID- 28504553
TI  - AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.
AB  - Adeno-associated virus (AAV) producer cell lines are created via transfection of
      HeLaS3 cells with a single plasmid containing three components (the vector
      sequence, the AAV rep and cap genes, and a selectable marker gene). As this
      plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded
      by the rep gene) elements required for site-specific integration, it was
      predicted that plasmid integration might occur within the AAVS1 locus on human
      chromosome 19 (chr19). The objective of this study was to investigate whether
      integration in AAVS1 might be correlated with vector yield. Plasmid integration
      sites within several independent cell lines were assessed via Southern,
      fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern
      analyses, the presence of fragments detected by both rep- and AAVS1-specific
      probes suggested that for several mid- and high-producing lines, plasmid DNA had
      integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes
      suggested that integration in AAVS1 was a more widespread phenomenon. High
      producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82]
      and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1,
      and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278
      (neither in AAVS1), while a total of three sites were identified in MW82 (two in
      AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid-
      and high-producing lines. In summary, the FISH, Southern, and PCR data provide
      evidence of site-specific integration of the plasmid within AAVS1 in several AAV
      producer cell lines. The data also suggest that integration in AAVS1 is a general
      phenomenon that is not necessarily restricted to high producers. The results also
      suggest that plasmid integration within the AAVS1 locus is not an absolute
      requirement for a high vector yield.

PMID- 28504554
TI  - How is patient care for multiple myeloma advancing?
AB  - INTRODUCTION: Treatment of multiple myeloma has undergone profound changes in the
      past years thanks to the increased understanding of the biology of the disease
      and the new treatment options. New drugs and effective approaches are currently
      available for the treatment of multiple myeloma, including immunomodulatory
      agents, proteasome inhibitors and autologous stem cell transplantation. Areas
      covered: We have described the recent updated criteria to start treatment in
      multiple myeloma and summarized clinical data from major studies including most
      recent agents. Particularly, results with pomalidomide, carfilzomib, ixazomib,
      monoclonal antibodies such as elotuzumab, daratumumab, and checkpoint inhibitors
      have been reported. Both transplant and non-transplant settings have been
      covered. Expert commentary: Despite the successful improvement in overall
      survival and time to relapse, multiple myeloma still remains incurable.
      Therefore, there is still an unmet need for new treatment strategies with novel
      mechanisms of action, like monoclonal antibodies, novel immunomodulators, and
      novel proteasome inhibitors. Implementation of these novel drugs in rationally
      designed therapies with a good balance of efficacy and safety should be carefully
      considered in order to improve outcome.

PMID- 28504556
TI  - Evolution of Technique in Laparoscopic Donor Nephrectomy: A Single Center
      Experience.
AB  - BACKGROUND: Renal transplantation is the most successful therapy for improving
      survival and quality of life for end-stage renal disease (ESRD). Living donor
      kidney transplantation (LDKTx) has been used as an alternative to reduce the stay
      on the waiting list of patients with ESRD. Laparoscopic donor nephrectomy (LDN)
      has become the standard procedure for LDKTx. OBJECTIVE: This study aims to
      describe evolution of surgical technique with LDN at our institute. MATERIALS AND
      METHODS: We retrospectively analyzed our experience with LDN performed from
      January, 2003 to November, 2016, focusing on describing modifications of the
      surgical technique and devices made during those years. Demographics, operative
      factors, and postoperative complications of donors were reviewed. RESULTS: From
      the beginning of our experience with LDKTx we have performed 185 cases. From 2003
      to 2016, 144 LDN were performed. Modifying our technique in response to the
      learning curve, complications encountered, and technological advancements, we
      experienced low complication rates. CONCLUSIONS: Continual refinement with LDN
      techniques based on intraoperative observations and technological advances is
      necessary to keep complication rates low and reduce donor morbidity and time for
      recovery.

PMID- 28504555
TI  - Frequency and characteristics of infusion reactions during biosimilar infliximab
      treatment in inflammatory bowel diseases: results from Central European
      nationwide cohort.
AB  - BACKGROUND: Safety data of the 'real life' use of an infliximab biosimilar, CT
      P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess
      the frequency and characteristics of infusion reactions during CT-P13 therapy in
      13 Hungarian and 1 Czech IBD centres. METHODS: Clinical and safety data was
      registered at fixed appointments. Trough levels and anti-drug antibody (ADA)
      concentration were measured by ELISA. Association between demographic, clinical,
      laboratory parameters and infusion reaction rates were evaluated statistically.
      RESULTS: Three hundred and eighty-four IBD patients were included. Twenty-eight
      Hungarian IBD patients (9.6%) developed infusion reaction during the treatment,
      64.3% of them was previously exposed to anti TNF therapy. No infusion reaction
      occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients
      who developed infusion reaction and was switched to adalimumab in 12 patients.
      However in 39.3% of patients developing infusion reaction CT-P13 therapy was
      continued with the use of premedication. Cumulative ADA positivity rates were
      8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure
      (30% vs. 3.1%, p < 0.001, OR 6.3 (2.7-14.6)) and ADA positivity (32.6% vs. 4.1%,
      p < 0.001, OR 19(5-73)) during the induction therapy were predictive factors for
      infusion reactions. CONCLUSIONS: Patients with previous exposure to anti-TNF
      alpha and ADA positivity during the induction therapy were more likely to develop
      infusion reactions.

PMID- 28504558
TI  - Nanoformulated water-soluble paclitaxel to enhance drug efficacy and reduce
      hemolysis side effect.
AB  - Surgery, chemotherapy, and radiotherapy are the three top cancer treatment
      modalities. Paclitaxel (PTX) is one of the most widely used chemotherapy drugs.
      However, its clinical applications have been significantly limited due to: (i)
      serious hemolysis effect of currently available commercial paclitaxel
      formulations and (ii) its water insolubility. An easy way to deliver paclitaxel
      by a new nanocarrier system using pluronic copolymers of P123/F68 and Sorbitan
      monopalmitate (Span 40) was reported in our previous research article. The
      characterization of the formulation and analysis of drug release and cellular
      uptake were also presented. In this article, we reported discoveries of our
      follow-up in vivo antitumor and in vitro hemolytic study discoveries. The
      experimental results showed that the nanoformulated PTX achieved much better
      tumor suppression performance while reducing hemolysis side effects. This newly
      formulated drug can significantly improve patient outcomes in cancer
      chemotherapy.

PMID- 28504557
TI  - Carotid angioplasty-assisted mechanical thrombectomy without urgent stenting may
      be a better option in acute tandem occlusions.
AB  - Background The aim of the study was to assess the efficacy of balloon angioplasty
      assisted mechanical thrombectomy without urgent stenting in the carotid artery as
      another approach for endovascular treatment of tandem occlusions. Methods Fifteen
      consecutive cases of tandem occlusions treated with the endovascular approach
      between January 2014 and May 2016 were reviewed. The study cohort included
      patients with an etiology of large vessel atherosclerosis. Extracranial carotid
      stenting was performed in another session if post-thrombectomy mRS modified
      Rankin Score (mRS) was 0-2. Good clinical outcome was determined by follow-up at
      7-10, 30 and 90 days according to the mRS. Results Most patients (80%) were male.
      Eight (53.4%) patients received intravenous thrombolysis before angiography.
      Proximal revascularization was successful in 100% of cases with balloon
      angioplasty internal carotid artery (ICA) origin. Successful recanalization
      (modified thrombolysis in cerebral infarction (mTICI) 2b-3) (mTICI 2 b-3)
      occurred in 12 cases (80%) and good clinical outcomes were achieved in 10
      patients (66.7%). Cervical ICA stent placement was performed in 10 patients with
      good clinical outcomes. No symptomatic intracranial hemorrhage occurred after
      delayed ICA stenting Conclusions This is the first reported case series to
      evaluate this approach for endovascular treatment of tandem occlusions. Carotid
      angioplasty-assisted mechanical thrombectomy without urgent stenting seems to be
      a safer approach.

PMID- 28504559
TI  - Immobilization of native type I collagen on polypropylene fabrics as a substrate
      for HepG2 cell culture.
AB  - Background/aims The critical part of a bio-artificial liver device is
      establishment of a bioreactor filled with liver cells. However, it is still
      unclear how to maintain benign cell function while achieving the sufficient cell
      quantity. In the current study, we aim to establish a novel carrier for the
      culture of HepG2 cells, a liver cell line, by modifying polypropylene nonwoven
      fabrics with native type I collagen. Methods "Piranha" solution, KH-550 and
      glutaraldehyde subsequently were used to bridge native type I collagen and
      polypropylene nonwoven fabrics. The type I collagen-coupled polypropylene
      nonwoven fabric was characterized by XPS, SEM, ATR-FTIR and water contact angle
      measurement. Furthermore, the biocompatibility between HepG2 cells and fiber film
      is evaluated by the ability of cell proliferation, albumin secretion, as well as
      urea synthesis. Results The coating of collagen onto polypropylene fabrics was
      more efficient using the chemical covalent binding method than direct immersion,
      which was validated by the presence of collagen-related elements and chemical
      bond. The adding of collagen in polypropylene fabrics promoted hydrophilicity and
      HepG2 cell adherence. Additionally, enhanced cell proliferation, increased
      albumin secretion and urea synthesis were observed in HepG2 cells growing on
      collagen-coated polypropylene fabrics. Conclusions The collagen coated
      polypropylene nonwoven fabrics, acting as a feasible substrate for HepG2 cell
      culture, may be used as a promising liver cell carrier for artificial liver
      reactor.

PMID- 28504560
TI  - Small RNA Functions Are Required for Growth and Development of Magnaporthe
      oryzae.
AB  - RNA interference (RNAi) is conserved in eukaryotic organisms, and it has been
      well studied in many animal and plant species and some fungal species, yet it is
      not well studied in fungal plant pathogens. In the rice blast fungus Magnaporthe
      oryzae, we examined small RNA (sRNA) and their biogenesis in the context of
      growth and pathogenicity. Through genetic and genomic analyses, we demonstrate
      that loss of a single gene encoding Dicer, RNA-dependent RNA polymerase, or
      Argonaute reduces sRNA levels. These three proteins are required for the
      biogenesis of sRNA-matching genome-wide regions (coding regions, repeats, and
      intergenic regions). The loss of one Argonaute reduced both sRNA and fungal
      virulence on barley leaves. Transcriptome analysis of multiple mutants revealed
      that sRNA play an important role in transcriptional regulation of repeats and
      intergenic regions in M. oryzae. Together, these data support that M. oryzae sRNA
      regulate developmental processes including, fungal growth and virulence.

PMID- 28504561
TI  - Sexual Violence and Intimate Partner Violence in College Women with a Mental
      Health and/or Behavior Disability.
AB  - OBJECTIVES: We address questions about (1) how college women with a disability
      experience sexual violence (SV) and intimate partner violence (IPV) across
      partners, including disability-specific abuse and (2) how SV/IPV impacts
      psychological, behavioral, physical, and academic life domains. METHODS/DESIGN:
      Twenty-seven female college students (mean age, 21.2; 66.6% white; 66.6%
      heterosexual) were randomly sampled from university registrar records. To be
      eligible for the study, students had to have at least one experience of SV/IPV
      since age 18 and a disability (88.8% reported one or more mental health
      conditions; 11.1% reported other conditions, such as attention deficit and
      hyperactivity disorder; with the majority of women indicating their disability
      preceded SV/IPV victimization). Using the Centers for Disease Control and
      Prevention's definitions of SV/IPV as guides, clinically trained master's level
      interviewers conducted semistructured interviews to ascertain SV/IPV patterns
      across students' three most recent relationships and related life impacts.
      RESULTS: SV/IPV was pervasive in college women with a disability, within hookup
      settings and/or recurring SV/IPV with a long-term partner. For some women, SV
      spanned multiple abusive partners. For women in relationships marked by chronic
      abuse, in addition to SV, the relationship dynamic included disability-specific
      abuse, social isolation, threats/intimidation, and technology-related abuse. For
      women experiencing SV events within hookup settings, alcohol was a common
      facilitator, with some abusers using a disability to manipulate a sexual
      connection. All but one participant reported exacerbated adverse mental health
      consequences (e.g., depression, anxiety, post-traumatic stress disorder, suicidal
      ideation/attempts, stress) after victimization. These adverse mental health
      consequences coincided with adverse behavioral (e.g., becoming less social,
      avoiding usual study lounge areas on campus), physical (e.g., problems sleeping,
      bruising, pregnancy concerns, and sexually transmitted disease), and academic
      outcomes (e.g., skipping and/or dropping class, grades suffering). DISCUSSION:
      Our results underscore the need for continued investment in campus programs that
      improve response to SV/IPV, including prevention programs and support services
      tailored to the specific needs and vulnerabilities of women with underlying
      mental health conditions.

PMID- 28504562
TI  - The animacy advantage for free-recall performance is not attributable to greater
      mental arousal.
AB  - People often demonstrate better memory for animate concepts (e.g., lion and
      sailor) than for inanimate concepts (e.g., hammer and mountain). Researchers have
      attributed this effect to an adaptive memory mechanism that favours information
      relevant for survival, including information about living things. In the present
      experiment, we examined the hypothesis that people demonstrate better free-recall
      performance for animate than inanimate words because animate words tend to be
      associated with greater mental arousal than inanimate words, a factor that was
      not controlled for in previous experiments on this topic. To this end, we matched
      animate and inanimate word lists on mental arousal (and several other factors),
      and compared participants' free-recall performance for the two word types. We
      were able to replicate past findings that participants' free-recall of animate
      words exceeds their free-recall of inanimate words, but we found no support for
      the possibility that the effect stems from differences in mental arousal between
      animate and inanimate concepts, as this effect maintained even when the word
      lists were matched on mental arousal. The present results therefore indicate that
      mental arousal cannot explain the effects of animacy on free-recall performance.

PMID- 28504564
TI  - Cinematic Rendering in CT: A Novel, Lifelike 3D Visualization Technique.
AB  - OBJECTIVE: The purpose of this article is to present an overview of cinematic
      rendering, illustrating its potential advantages and applications. CONCLUSION:
      Volume-rendered reconstruction, obtaining 3D visualization from original CT
      datasets, is increasingly used by physicians and medical educators in various
      clinical and educational scenarios. Cinematic rendering is a novel 3D rendering
      algorithm that simulates the propagation and interaction of light rays as they
      pass through the volumetric data, showing a more photorealistic representation of
      3D images than achieved with standard volume rendering.

PMID- 28504565
TI  - Early, intensive statin treatment reduces 'hard' cardiovascular outcomes after
      acute coronary syndrome.
AB  - Background Early, intensive statin treatment is the standard of care after acute
      coronary syndrome (ACS). However, the benefit of this approach to prevent major
      adverse cardiovascular events has been demonstrated in only one randomised,
      placebo controlled trial. The Myocardial Ischemia Reduction with Aggressive
      Cholesterol Lowering (MIRACL) trial demonstrated that atorvastatin 80 mg daily,
      compared with placebo, reduced time to first occurrence of death, non-fatal
      myocardial infarction, resuscitated cardiac arrest, or hospitalisation for
      unstable angina (stroke not included) during the 16 week period following ACS.
      However, there were no significant effects on individual components of the
      composite endpoint except unstable angina. This led some to question whether
      early, intensive statin treatment reduces 'hard' events after ACS. Aim The burden
      of coronary heart disease after ACS, and therefore the efficacy of its treatment,
      depends not only on the occurrence of one ischaemic event, but rather on
      cumulative events experienced by patients. Accordingly, we conducted a post-hoc
      analysis of the MIRACL trial to examine the effect of atorvastatin on first as
      well as recurrent (i.e. total) hard cardiovascular events after ACS (death,
      myocardial infarction, stroke, and resuscitated cardiac arrest). Methods and
      Results In the 3086 patients who comprised the MIRACL trial, atorvastatin 80 mg
      did not reduce time to first hard event compared with placebo (hazard ratio 0.89,
      95% confidence interval 0.72-1.10, P = 0.27). However, atorvastatin significantly
      reduced total hard events (hazard ratio 0.80, 95% confidence interval 0.66-0.97,
      P = 0.03). To prevent one hard event during the 16 weeks following ACS, only 11
      patient-years of treatment with atorvastatin were required. Conclusion Early,
      intensive treatment with atorvastatin is an efficient intervention to reduce hard
      cardiovascular events after ACS.

PMID- 28504563
TI  - PET Molecular Imaging-Directed Biopsy: A Review.
AB  - OBJECTIVE: The purpose of this review is to summarize the applications of PET
      molecular imaging-directed biopsy of a variety of organs in the management of
      various diseases with a focus on cancers. CONCLUSION: PET can yield metabolic
      information at the cellular and molecular levels, and PET-directed biopsy is
      playing an increasing role in the diagnosis and staging of diseases.

PMID- 28504566
TI  - Influence of Lactobacillus reuteri L26 BiocenolTM on immune response against
      porcine circovirus type 2 infection in germ-free mice.
AB  - Probiotic bacteria are frequently used for prevention of bacterial infections of
      the gastrointestinal tract, but there are only limited studies on their efficacy
      against viral gut infections in animals. The aim of this study was to investigate
      the effect of probiotic Lactobacillus reuteri L26 BiocenolTM on the innate and
      adaptive immune responses in germ-free Balb/c mice, experimentally infected by
      porcine circovirus type 2 (PCV2), which confers immunosuppressive effect. A total
      of 30 six-week-old female mice were divided into 3 groups and animals in
      experimental group LPCV (n=10) were inoculated with L. reuteri L26, animals in
      the control group (C; n=10) and experimental group PCV (n=10) received sterile De
      Man-Rogosa-Sharpe broth for 7 days. Subsequently, mice from both experimental
      groups were infected with PCV2; however, mice in the control group received virus
      cultivation medium (mock). Virus load in faeces, ileum and mesenteric lymph nodes
      (MLN); as well as gene expression of selected cytokines, immunoglobulin A (IgA)
      and polymeric Ig receptor (PIgR) in the ileum, and percentage of CD8+, CD19+ and
      CD49b+CD8- cells in the MLN were evaluated. Our results showed that L. reuteri
      significantly decreased the amount of PCV2 in faeces and in the ileum, and up
      regulated the gene expression of chemokines, interferon (IFN)-gamma, IgA and PIgR
      in the ileum. Increased IFN-gamma mRNA level was accompanied by higher proportion
      of natural killer cells and up-regulated IgA and PIgR gene expressions were in
      accordance with significantly higher percentage of CD19+ lymphocytes in the MLN.
      These findings indicate that probiotic L. reuteri has an antiviral effect on PCV2
      in the intestine which is mediated by stimulation of local gut immune response.

PMID- 28504567
TI  - Effects of Lactobacillus casei CCFM419 on insulin resistance and gut microbiota
      in type 2 diabetic mice.
AB  - The antidiabetic effect of Lactobacillus is increasingly recognized worldwide. In
      this research, the hypoglycemic activity of Lactobacillus casei CCFM419 was
      investigated in mice with high-fat and low-dose streptozotocin induced type 2
      diabetes. Oral L. casei CCFM419 administration favourably regulated blood glucose
      balance, increased glucose tolerance and protected islets in the diabetic mice,
      accompanied by an improvement in lipid metabolism. The homeostasis model of
      insulin resistance, insulin level and insulin tolerance test and mRNA expression
      of PI3K/Akt signalling pathway indexes revealed that L. casei CCFM419 had a
      positive effect on insulin resistance. Furthermore, treatment with L. casei
      CCFM419 recovered the level of short-chain fatty acids and increased the
      abundance of butyrate-producing bacteria, such as Allobaculum and Bacteriodes.
      These results demonstrated that L. casei CCFM419 had the potential ability to
      ameliorate insulin resistance and hyperglycaemic in type 2 diabetic mice through
      underlying PI3K/Akt signalling pathway and short-chain fatty acids/gut microbiota
      pathways.

PMID- 28504568
TI  - Lactobacillus rhamnosus CRL1505 nasal administration improves recovery of T-cell
      mediated immunity against pneumococcal infection in malnourished mice.
AB  - Immunobiotic lactic acid bacteria have become an interesting alternative for the
      prevention of respiratory infections. Previously, we demonstrated that the nasal
      administration of Lactobacillus rhamnosus CRL1505, during repletion of
      malnourished mice, resulted in diminished susceptibility to the challenge with
      the respiratory pathogen Streptococcus pneumoniae. Considering the known
      alterations induced by malnutrition on T lymphocytes and the importance of this
      cell population on the protection against respiratory pathogens, we aimed to
      study the effect of L. rhamnosus CRL1505 nasal administration on the recovery of
      T cell-mediated defences against pneumococcal infection in malnourished mice
      under nutritional recovery. Malnourished mice received a balanced conventional
      diet (BCD) for seven days or BCD for seven days with nasal L. rhamnosus CRL1505
      supplementation during last two days of the treatment. After the treatments mice
      were infected with S. pneumoniae. Flow cytometry studies were carried out in bone
      marrow, thymus, spleen and lung to study T cells, and Th1/Th2 cytokine profiles
      were determined in broncho-alveolar lavages and serum. The administration of
      CRL1505 strain to malnourished mice under recovery reduced quantitative and
      qualitative alterations of CD4+ T cells in the bone marrow, thymus, spleen and
      lung induced by malnutrition. In addition, CRL1505 treatment augmented Th2
      cytokines (interleukin 10 and 4) in respiratory and systemic compartments after
      pneumococcal infection. These results show that modulation of CD4+ T lymphocytes
      induced by L. rhamnosus CRL1505 has an important role in the beneficial effect
      induced by this strain on the recovery of malnourished mice. These data also
      indicate that nasally administered L. rhamnosus CRL1505 may represent a non
      invasive alternative to modulate and improve the T cell-mediated immunity against
      respiratory pathogens in immunocompromised malnourished hosts.

PMID- 28504569
TI  - Comparisons for Effectiveness of Aromatherapy and Acupressure Massage on Quality
      of Life in Career Women: A Randomized Controlled Trial.
AB  - OBJECTIVES: This study was aimed to compare the effectiveness of aromatherapy and
      acupressure massage intervention strategies on the sleep quality and quality of
      life (QOL) in career women. DESIGN: The randomized controlled trial experimental
      design was used in the present study. One hundred and thirty-two career women (24
      55 years) voluntarily participated in this study and they were randomly assigned
      to (1) placebo (distilled water), (2) lavender essential oil (Lavandula
      angustifolia), (3) blended essential oil (1:1:1 ratio of L. angustifolia, Salvia
      sclarea, and Origanum majorana), and (4) acupressure massage groups for a 4-week
      treatment. The Pittsburgh Sleep Quality Index and Short Form 36 Health Survey
      were used to evaluate the intervention effects at pre- and postintervention.
      RESULTS: After a 4-week treatment, all experimental groups (blended essential
      oil, lavender essential oil, and acupressure massage) showed significant
      improvements in sleep quality and QOL (p < 0.05). Significantly greater
      improvement in QOL was observed in the participants with blended essential oil
      treatment compared with those with lavender essential oil (p < 0.05), and a
      significantly greater improvement in sleep quality was observed in the
      acupressure massage and blended essential oil groups compared with the lavender
      essential oil group (p < 0.05). CONCLUSIONS: The blended essential oil exhibited
      greater dual benefits on improving both QOL and sleep quality compared with the
      interventions of lavender essential oil and acupressure massage in career women.
      These results suggest that aromatherapy and acupressure massage improve the sleep
      and QOL and may serve as the optimal means for career women to improve their
      sleep and QOL.

PMID- 28504570
TI  - Saliva: a reliable sample matrix in bioanalytics.
AB  - Saliva is gaining increasing attention as a bioanalytical sample matrix. Mostly
      because of the easy and noninvasive collection, it is not only beneficial in
      endocrinological and behavioral science, but also in pediatrics. Saliva also has
      the advantage of being the only body fluid which can be collected even during
      physical exercise, for example, during sportive activities, and there are
      physiological characteristics that make it superior to serum/plasma or urine for
      specific scientific questions. This review provides an insight into the
      physiology of saliva formation, explaining how certain compounds enter this
      bodily fluid, and gives advice for collection, storage and analytical methods.
      Finally, it presents a number of reliable and proven applications for saliva
      analysis from scientific fields including endocrinology, sports medicine,
      forensics and immunology.

PMID- 28504571
TI  - The Legend of the Luschka Tubercle and Its Association With Snapping Scapulae:
      Osseous Morphology of Snapping Scapulae on CT Images.
AB  - OBJECTIVE: The purpose of this article is to determine the osseous morphology of
      snapping scapulae on CT images. MATERIALS AND METHODS: Retrospectively, 2D and 3D
      CT images of the scapulae of 35 patients with snapping scapula were compared with
      35 age-matched control group subjects. Two observers analyzed the following
      parameters: presence of the Luschka tubercle; abnormalities of the bones and
      periscapular soft tissues; shape, thickness, and length of the superior angle of
      the scapula; craniocaudal length of the scapula; minimum distance between the
      scapula and rib cage; depth of the subscapular fossa; and the superomedial angle.
      RESULTS: In patients with snapping scapulae, observer 1 did not find any Luschka
      tubercles, whereas observer 2 detected one; in the control group both observers
      found two Luschka tubercles (p > 0.49). One scapular osteochondroma was found in
      the group with snapping scapulae. No further abnormalities of the rib cage or
      periscapular soft tissues were found in that group. The superior angle of the
      scapula was significantly thicker in the snapping scapula group compared with the
      control group (4.8 +/- 1.3 mm vs 4.0 +/- 1.0 mm, p < 0.012). The subscapular
      fossa was significantly deeper in patients with snapping scapula than in control
      group subjects (25.7 +/- 5.2 mm vs 21.8 +/- 5.0 mm, p < 0.005). The remaining
      parameters did not differ significantly between the groups. CONCLUSION: The
      Luschka tubercle was rarely observed and not associated with a snapping scapula.
      However, the superior angle of the scapula was significantly thicker and the
      subscapular fossa was significantly deeper in patients with snapping scapula than
      in control group subjects.

PMID- 28504572
TI  - Screening Mammography for Women in Their 40s: The Potential Impact of the
      American Cancer Society and U.S. Preventive Services Task Force Breast Cancer
      Screening Recommendations.
AB  - OBJECTIVE: The purpose of this study was to review screening mammograms obtained
      in one practice with the primary endpoint of determining the rate of detection of
      breast cancer and associated prognostic features in women 40-44 and 45-49 years
      old. MATERIALS AND METHODS: The retrospective cohort study included women in
      their 40s with breast cancer detected at screening from June 2014 through May
      2016. The focus was on cancer detection rate, pathologic findings, and risk
      factors. RESULTS: A total of 32,762 screens were performed, and 808 biopsies were
      recommended. These biopsies yielded 224 breast cancers (cancer detection rate,
      6.84 per 1000 screens). Women 40-49 years old had 18.8% of cancers detected; 50
      59 years, 21.8%; 60-69 years, 32.6%; and 70-79 years, 21.4%. Among the 40- to 49
      year-old women, women 40-44 years old underwent 5481 (16.7%) screens, had 132
      biopsies recommended, and had 20 breast cancers detected (cancer detection rate,
      3.6/1000). Women 45-49 years old underwent 5319 (16.2%) screens, had 108 biopsies
      recommended, and had 22 breast cancers detected (cancer detection rate,
      4.1/1000). Thus, women 40-44 years old had 8.9% and women 45-49 years old had
      9.8% of all screen-detected breast cancers. Of these only a small percentage of
      women with detected cancers had a first-degree relative with breast cancer (40-44
      years, 15%; 45-49 years, 32%) or a BRCA mutation (40-44 years, 5%; 45-49 years,
      5%), and over 60% of the cancers were invasive. CONCLUSION: Women 40-49 years old
      had 18.8% of all screen-detected breast cancers. The two cohorts (40-44 and 45-49
      years old) had similar incidences of screen-detected breast cancer (8.9%, 9.8%)
      and cancer detection rates within performance benchmark standards, supporting a
      similar recommendation for both cohorts and the American College of Radiology
      recommendation of annual screening mammography starting at age 40.

PMID- 28504574
TI  - Gut dysbiosis following C-section instigates higher colonisation of toxigenic
      Clostridium perfringens in infants.
AB  - Herein we investigated the intestinal carriage of alpha-toxigenic and
      enterotoxigenic Clostridium perfringens during infancy, focusing on its
      association with other gut microbes and mode of delivery and feeding. Faecal
      samples from 89 healthy term infants were collected at age 7 days, 1 month, 3
      months, 6 months and 3 years. C. perfringens was quantified by qPCR; other gut
      bacteria were quantified by reverse-transcription-qPCR. Alpha-toxigenic C.
      perfringens was detected in 3.4% infants at day 7 but was present in 35-40%
      infants at subsequent time-points, with counts ranging from 103-107 cells/g
      faeces. Enterotoxigenic C. perfringens remained undetected at day 7 but was
      detected in 1.1, 4.5, 10.1 and 4.5% infants at 1 month, 3 months, 6 months and 3
      years, respectively. Intriguingly, infants carrying alpha-toxigenic C.
      perfringens had lower levels of Bacteroides fragilis group, bifidobacteria,
      lactobacilli and organic acids as compared to non-carriers. Further analyses
      revealed that, compared to vaginally-born infants, caesarean-born infants had
      higher carriage of C. perfringens and lower levels of B. fragilis group,
      bifidobacteria, lactobacilli and faecal organic acids during first 6 months.
      Compared to formula-fed infants, breast-fed infants were slightly less often
      colonised with C. perfringens; and within caesarean-born infants, breast-fed
      infants had slightly lower levels of C. perfringens and higher levels of B.
      fragilis group, bifidobacteria, and lactobacilli than formula-fed infants. This
      study demonstrates the quantitative dynamics of toxigenic C. perfringens
      colonisation in infants during the early years of life. Caesarean-born infants
      acquire a somewhat perturbed microbiota, and breast-feeding might be helpful in
      ameliorating this dysbiosis. Higher carriage of toxigenic C. perfringens in
      healthy infants is intriguing and warrants further investigation of its sources
      and clinical significance in infants, particularly the caesarean-born who may
      represent a potential reservoir of this opportunistic pathogen and might be more
      prone to associated illnesses.

PMID- 28504573
TI  - Human Norovirus and Its Surrogates Induce Plant Immune Response in Arabidopsis
      thaliana and Lactuca sativa.
AB  - Human norovirus is the leading cause of foodborne illness worldwide with the
      majority of outbreaks linked to fresh produce and leafy greens. It is essential
      that we thoroughly understand the type of relationship and interactions that take
      place between plants and human norovirus to better utilize control strategies to
      reduce transmission of norovirus in the field onto plants harvested for human
      consumption. In this study the expression of gene markers for the salicylic acid
      (SA) and jasmonic acid (JA) plant defense pathways was measured and compared in
      romaine lettuce (Lactuca sativa) and Arabidopsis thaliana Col-0 plants that were
      inoculated with Murine Norovirus-1, Tulane Virus, human norovirus GII.4, or
      Hank's Balanced Salt Solution (control). Genes involving both the SA and JA
      pathways were expressed in both romaine lettuce and A. thaliana for all three
      viruses, as well as controls. Studies, including gene expression of SA- and JA
      deficient A. thaliana mutant lines, suggest that the JA pathway is more likely
      involved in the plant immune response to human norovirus. This research provides
      the first pieces of information regarding how foodborne viruses interact with
      plants in the preharvest environment.

PMID- 28504576
TI  - Is the role of human female reproductive tract microbiota underestimated?
AB  - An issue that is currently undergoing extensive study is the influence of human
      vaginal microbiota (VMB) on the health status of women and their neonates.
      Healthy women are mainly colonised with lactobacilli such as Lactobacillus
      crispatus, Lactobacillus jensenii, and Lactobacillus iners; however, other
      bacteria may be elements of the VMB, particularly in women with bacterial
      vaginosis. The implementation of culture-independent molecular methods in VMB
      characterisation, especially next-generation sequencing, have provided new
      information regarding bacterial diversity in the vagina, revealing a large number
      of novel, fastidious, and/or uncultivated bacterial species. These molecular
      studies have contributed new insights regarding the role of bacterial community
      composition. In this study, we discuss recent findings regarding the reproductive
      tract microbiome. Not only bacteria but also viruses and fungi constitute
      important components of the reproductive tract microbiome. We focus on aspects
      related to the impact of the maternal microbiome on foetal development, as well
      as the establishment of the neonatal microbiomes, including the placenta
      microbiome, and the haematogenous source of intrauterine infection. We also
      discuss whether the role of the vaginal microbiome is currently understood and
      appreciated.

PMID- 28504575
TI  - Alleviation of enterotoxigenic Escherichia coli challenge by recombinant
      Lactobacillus plantarum expressing a FaeG- and DC-targeting peptide fusion
      protein.
AB  - FaeG is the major subunit of K88 fimbriae. These cell surface attachments are
      considered to be the major virulence factor of enterotoxigenic Escherichia coli
      (ETEC), which causes diarrhoea in piglets. The use of dendritic cell-targeting
      peptide (DCpep) has been demonstrated to be an effective approach to enhance the
      immunity of vaccines. Lactobacillus plantarum is an attractive candidate for oral
      vaccination owing to its beneficial effects and safety. In this study, L.
      plantarum was employed to deliver a FaeG-DCpep fusion antigen, and the immune
      response in mice was evaluated. The synthesis of FaeG-DCpep dramatically
      increased the adhesion of recombinant L. plantarum (RLP) to IPEC-J2 cell
      surfaces, resulting in direct competition between L. plantarum and ETEC during
      adhesion assays. Significantly higher levels of body weight gain, sera
      immunoglobulin G and intestinal immunoglobulin A were observed in BALB/c mice
      immunised with RLP. In addition, the number of CD19+ B cells and CD11c+DC cells
      and the expression levels of several cytokines in the spleen and lymph nodes
      increased significantly compared to non-immunised mice. The oral administration
      of RLP also alleviated the symptoms of ETEC challenge, as shown by haematoxylin
      eosin staining, indicating that RLP may be an efficient vaccine candidate.

PMID- 28504577
TI  - Lactobacillus fermentum IM12 attenuates inflammation in mice by inhibiting NF
      kappaB-STAT3 signalling pathway.
AB  - In the present study, we isolated Lactobacillus fermentum IM12 from human gut
      microbiota, which strongly inhibited interleukin (IL)-6 expression and STAT3
      activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages,
      and examined its anti-inflammatory effect in mice with carrageenan-induced hind
      paw oedema (CIE) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis
      (TIC). Oral administration of IM12 (0.2*109, 1*109 or 5*109 cfu/mouse, once a day
      for 3 days) in mice with CIE significantly suppressed the increase of oedema
      volume and thickness, as well as myeloperoxidase activity and IL-6, IL-17, NO,
      and prostaglandin E2 levels in the carrageenan-stimulated paw. Treatment with
      IM12 (1*109 cfu/mouse, once a day for 3 days) in mice with TIC significantly
      suppressed colon shortening, and myeloperoxidase activity and IL-6 and IL-17
      levels. Treatment with IM12 in mice with CIE or TIC also suppressed the
      expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, as well as
      activation of nuclear factor kappa beta (NF-kappaB) and signal transducer and
      activator of transcription 3 (STAT3). Furthermore, IM12 significantly inhibited
      the expression of iNOS, and COX-2, as well as activation of NF-kappaB in LPS
      stimulated mouse peritoneal macrophages. The inflammatory effect of heat
      inactivated IM12 was significantly different to that of live IM12 in mice with
      TIC, although anti-inflammatory effect of IM12 was reduced by heat treatment.
      Based on these findings, IM12 may attenuate inflammation by inhibiting NF-kappaB
      STAT3 signalling pathway.

PMID- 28504578
TI  - Effects of dietary chitosan on growth, lipid metabolism, immune response and
      antioxidant-related gene expression in Misgurnus anguillicaudatus.
AB  - This study was performed to evaluate the effects of dietary chitosan
      supplementation on growth performance, lipid metabolism, gut microbial,
      antioxidant status and immune responses of juvenile loach (Misgurnus
      anguillicaudatus). Five experimental diets were formulated to contain graded
      levels of chitosan (0 (control), 0.5, 1, 2 and 5% CHI) for 50 days. Results of
      the present study showed that body weight gain was significantly higher in fish
      fed chitosan supplemented diets in dose dependent manner than control group.
      Increasing dietary chitosan levels reduced gut lipid content. Meanwhile the mRNA
      expression levels of intestine lipoprotein lipase and fatty acid binding protein
      2 were significantly reduced with incremental dietary chitosan level. The
      percentages of total monounsaturated fatty acid decreased, while polyunsaturated
      fatty acid increased with dietary chitosan. The fish fed 0.5% CHI had higher
      mucus lysozyme activity (LZM) than those fed 0% CHI, but the LZM activity was
      significantly decreased with advancing chitosan supplement. The expression levels
      of superoxide dismutase, catalase and glutathione peroxidase revealed a similar
      trend, where the highest expressions were found in fish fed 5% CHI diet. In the
      term of intestine microbiota between 0 and 1% CHI groups, the proportion of
      bacteria in the phylum Bacteroidetes increased, whereas the proportion of
      bacteria in the phylum Firmicutes decreased as the fish supplemented chitosan. In
      conclusion, supplementation of chitosan improved growth performance, antioxidant
      status and immunological responses in loach.

PMID- 28504579
TI  - Exopolysaccharide-producing Streptococcus thermophilus CRL1190 reduces the
      inflammatory response caused by Helicobacter pylori.
AB  - This work evaluated the ability of the probiotic Streptococcus thermophilus
      CRL1190 strain and its exopolysaccharides to adhere to gastric mucosa. Probiotic
      bacteria attachment to the human stomach epithelium was confirmed in human
      stomach tissue samples and the gastric epithelial cell line AGS. In addition, it
      was demonstrated that S. thermophilus CRL1190 strain reduced Helicobacter pylori
      adhesion and attenuated inflammatory response in AGS cells. This is the first
      demonstration of the capacity of S. thermophilus CRL1190 to adhere to the stomach
      gastric mucosa, and improve protection against H. pylori through the reduction of
      its adhesion and the modulation of the inflammatory response. Therefore, S.
      thermophilus CRL1190 fermented milk is a good candidate for further in vivo
      studying of the protective effect of functional food against H. pylori infection
      and gastric inflammatory damage.

PMID- 28504580
TI  - Intragastric administration of Lactobacillus casei BL23 induces regulatory
      FoxP3+RORgammat+ T cells subset in mice.
AB  - Many studies have highlighted the immunomodulatory properties of the probiotic
      strain Lactobacillus casei BL23. Recently, we demonstrated the ability of this
      strain to modulate the Th2-oriented immune response in a mouse model of cow's
      milk allergy based on the induction of a Th17-biased immune response. The
      probiotic function of L. casei has been also linked to gut-microbiota
      modifications which could been potentially involved in the immune regulation;
      however, its precise mechanism of action remains poorly understood. In this
      regard, recent studies suggest that gut microbiota induces a specific subset of
      CD4+FoxP3+ Treg cells that also express RORgammat+, the specific transcription
      factor of Th17 cells. This new type of regulatory T cells, called type 3 Treg,
      displays suppressive function during intestinal inflammation, participating in
      inflammation control. We thus explored the ability of L. casei BL23 to
      specifically induce type 3 Treg cells, both in vitro and in vivo. Our results
      showed that intragastric administration of L. casei BL23 to mice induces local
      and systemic FoxP3+ RORgammat+ type 3 Treg cells that could then participate in
      the beneficial effects of L. casei BL23 in different intestinal-related
      disorders.

PMID- 28504581
TI  - Bacillus coagulans GBI-30, 6086 increases plant protein digestion in a dynamic,
      computer-controlled in vitro model of the small intestine (TIM-1).
AB  - The aim of this study was to assess the potential of the probiotic Bacillus
      coagulans GBI-30, 6086 [GanedenBC30] (BC30) to aid in protein digestion of
      alimentary plant proteins. To test this, three plant proteins, from pea, soy and
      rice, were digested in a validated in vitro model of the stomach and small
      intestine (TIM-1) in the absence and in the presence of BC30. Samples were taken
      from the TIM-1 fractions that mimic uptake of amino acids by the host and
      analysed for alpha-amino nitrogen (AAN) and total nitrogen (TN). Both were
      increased by BC30 for all three plant proteins sources. The ratio of TN/AAN
      indicated that for pea protein digestion was increased by BC30, but the degree of
      polymerisation of the liberated small peptides and free amino acids was not
      changed. For soy and rice, however, BC30 showed a 2-fold reduction in the TN/AAN
      ratio, indicating that the liberated digestion products formed during digestion
      in the presence of BC30 were shorter peptides and more free amino acids, than
      those liberated in the absence of BC30. As BC30 increased protein digestion and
      uptake in the upper gastrointestinal (GI) tract, it consequently also reduced the
      amount of protein that would be delivered to the colon, which could there be
      fermented into toxic metabolites by the gut microbiota. Thus, the enhanced
      protein digestion by BC30 showed a dual benefit: enhanced amino acid
      bioavailability from plant proteins in the upper GI tract, and a healthier
      environment in the colon.

PMID- 28504582
TI  - Endoscopic Clip MRI Screening: A Canada-Wide Policy Survey.
AB  - OBJECTIVE: Not all endoscopically placed clips are MRI compatible, so screening
      for endoscopic clips before MRI is recommended. The purpose of this study was to
      assess endoscopic clip screening practices at Canadian MRI centers, including
      number of centers that screen, specific screening methods, perceived safety of
      endoscopic clip models, and practices for dealing with confirmed gastrointestinal
      endoscopic clips. MATERIALS AND METHODS: A bilingual online survey was
      distributed to Canadian MRI centers to assess site demographics, endoscopic clip
      screening practices, safety considerations for different endoscopic clip models,
      protocols for dealing with patients with endoscopic clips, and the perceived
      value of screening. One year later, a secondary survey was distributed to the
      original participants to assess for changes made to screening policy after the
      initial survey and to assess awareness of any complications arising from the
      presence of endoscopic clips during MRI. RESULTS: Sixty-seven MRI centers
      completed the survey (55% response rate). Sixteen centers (24%) did not
      specifically screen for endoscopic clips, five because they were not aware that
      endoscopic clips may not be safe for MRI. Fifty-one centers (76%) did screen for
      endoscopic clips. At least 23% of screeners misclassified the safety of one or
      more MRI-unsafe clips. As many as 36% of screeners may perform MRI on patients
      with confirmed gastrointestinal endoscopic clips; 16% reschedule for more than 6
      weeks after endoscopy; and 18% limit the field strength to 1.5 T, the safety of
      which is uncertain. CONCLUSION: Many Canadians are undergoing MRI without
      screening for endoscopic clips. Although the risks of MRI to patients with
      endoscopic clips is unclear, the misclassification of some endoscopic clip models
      and inconsistent protocols for dealing with confirmed endoscopic clips call for
      further research and unified evidence-based endoscopic clip screening standards.

PMID- 28504583
TI  - Repeated failures to obtain selective directed forgetting in lab and online
      samples and variations in stimuli.
AB  - Previous research has produced mixed findings as to whether it is possible to
      selectively forget a subset of items while maintaining access to the remaining
      items from the same episode, using a modified version of the list-method directed
      forgetting (LMDF) paradigm. The present study includes six attempts to obtain the
      selective directed forgetting (SDF) effect with the aim of exploring its
      underlying mechanisms. However, despite variations in the stimuli and samples,
      which included both lab and online participants, we failed to obtain SDF across
      five experiments. In one of the experiments, we observed what appeared to be an
      SDF effect; however, the unexpected baseline differences across the conditions
      make the interpretation of this result equivocal. In contrast, standard directed
      forgetting effect was obtained when an LMDF condition was included in the design.
      An evaluation of the previous literature in combination with the present study
      raises questions about the reliability of the SDF phenomenon.

PMID- 28504584
TI  - Silvanus Phillips Thompson on Perception.

PMID- 28504585
TI  - Seven- to 11-Year-Olds' Developing Ability to Recognize Natural Facial
      Expressions of Basic Emotions.
AB  - Being able to recognize facial expressions of basic emotions is of great
      importance to social development. However, we still know surprisingly little
      about children's developing ability to interpret emotions that are expressed
      dynamically, naturally, and subtly, despite real-life expressions having such
      appearance in the vast majority of cases. The current research employs a new
      technique of capturing dynamic, subtly expressed natural emotional displays
      (happy, sad, angry, shocked, and disgusted). Children aged 7, 9, and 11 years
      (and adults) were systematically able to discriminate each emotional display from
      alternatives in a five-way choice. Children were most accurate in identifying the
      expression of happiness and were also relatively accurate in identifying the
      expression of sadness; they were far less accurate than adults in identifying
      shocked and disgusted. Children who performed well academically also tended to be
      the most accurate in recognizing expressions, and this relationship maintained
      independently of chronological age. Generally, the findings testify to a well
      developed ability to recognize very subtle naturally occurring expressions of
      emotions.

PMID- 28504587
TI  - A Single Intercostal Space Thoracoscopic Approach for Minimally Invasive Ivor
      Lewis Esophagectomy.
AB  - OBJECTIVE: We present a laparoscopic and single intercostal space thoracoscopic
      approach (SICS group) for Ivor Lewis minimally invasive esophagectomy (MIE) and
      provide postoperative analgesia with a continuous multiple intercostal nerve
      blocking technique. The characters of this technique are evaluated. MATERIALS AND
      METHODS: From October 2015 to April 2016, 18 consecutive patients with esophageal
      cancer were treated with Ivor Lewis MIE by a SICS group. Moreover, from July 2014
      to September 2015, 48 patients with esophageal cancer received Ivor Lewis MIE by
      four-port video-assisted thoracic surgery (VATS) approach. Among those patients,
      by using propensity-score matching, 18 matched patients who underwent four-port
      VATS MIE (four-port group) were retrospectively selected for further statistical
      analysis. Patient demographics, short-term postoperative outcomes were recorded.
      RESULTS: None of the patients in the SICS group required conversion to an open
      procedure. No failure of the intrathoracic esophagogastrostomy occurred. No
      perioperative mortality or readmission was observed in this series. No patient
      suffered from anastomotic leak or complained remarkable dysphasia during follow
      up. SICS group had a shorter duration of both docking procedure and closure of
      chest incisions compared with four-port group. The visual analog scale (VAS) pain
      scores on 24 hours after surgery was significantly lower in SICS group than in
      four-port group, while the values on 6 hours were comparable. The level of
      creatine kinase on postoperative day (POD) 1 was significantly lower in SICS
      group than in four-port group. CONCLUSION: Single intercostal space thoracoscopic
      procedure is safe and technically feasible and can therefore be viewed as an
      attractive alternative approach for performing Ivor Lewis MIE.

PMID- 28504588
TI  - The Impact of Corruption on Population Health.

PMID- 28504591
TI  - Theiler's Murine Encephalomyelitis Virus.

PMID- 28504590
TI  - Winning the BIG Medals.

PMID- 28504589
TI  - Analysis of Saliva Gene Expression during Head and Neck Cancer Radiotherapy: A
      Pilot Study.
AB  - Saliva, a biological fluid, is a promising candidate for novel approaches to
      prognosis, clinical diagnosis, monitoring and management of patients with both
      oral and systemic diseases. However, to date, saliva has not been widely
      investigated as a biomarker for radiation exposure. Since white blood cells are
      also present in saliva, it should theoretically be possible to investigate the
      transcriptional biomarkers of radiation exposure classically studied in whole
      blood. Therefore, we collected whole blood and saliva samples from eight head and
      neck cancer patients before the start of radiation treatment, at mid-treatment
      and after treatment. We then used a panel of five genes: BAX, BBC3, CDKN1A, DDB2
      and MDM2, designated for assessing radiation dose in whole blood to evaluate gene
      expression changes that can occur during radiotherapy. The results revealed that
      the expression of the five genes did not change in whole blood. However, in
      saliva, CDKN1A and DDB2 were significantly overexpressed at the end, compared to
      the start, of radiotherapy, and MDM2 was significantly underexpressed between mid
      treatment and at the end of treatment. Interestingly, CDKN1A and DDB2 expressions
      also showed an increasing monotonic relationship with total radiation dose
      received during radiotherapy. To our knowledge, these results show for the first
      time the ability to detect gene expression changes in saliva after head and neck
      cancer radiotherapy, and pave the way for further promising studies validating
      saliva as a minimally invasive means of biofluid collection to directly measure
      radiation dose escalation during treatment.

PMID- 28504592
TI  - Hungers that Need Feeding: On the Normativity of Mindful Nourishment.
AB  - Drawing on participant observation in a 'mindful weight loss' course offered in
      the Netherlands, this paper explores the normative register through which
      mindfulness techniques cast people in relation to concerns with overeating and
      body weight. The women seeking out mindfulness use eating to cope with troubles
      in their lives and are hindered by a preoccupation with the size of their bodies.
      Mindfulness coaches aim to help them let go of this 'struggle with eating' by
      posing as the central question: 'what do I really hunger after?' The self's
      hungers include 'belly hunger' but also stem from mouths, hearts, heads, noses
      and eyes. They cannot all be fed by food. The techniques detailed in this paper
      focus on recognizing and disentangling one's hungers; developing self-knowledge
      of and a sensitivity to what 'feeds' one's life; and the way one positions
      oneself in relation to oneself and the world. While introducing new norms, the
      course configures 'goods' and 'bads' in different ways altogether, shaping the
      worlds people come to inhabit through engaging in self-care. In particular, the
      hungering body is foregrounded as the medium through which life is lived. Taking
      a material semiotic approach, this paper makes an intervention by articulating
      the normative register of nourishment in contrast to normalization. Thus, it
      highlights anthropologists' potential strengthening of different ways of doing
      normativity.

PMID- 28504593
TI  - Comparison Between Digital and Synthetic 2D Mammograms in Breast Density
      Interpretation.
AB  - OBJECTIVE: The purpose of this study was to compare assessments of breast density
      on synthetic 2D images as compared with digital 2D mammograms. MATERIALS AND
      METHODS: This retrospective study included consecutive women undergoing screening
      with digital 2D mammography and tomosynthesis during May 2015 with a negative or
      benign outcome. In separate reading sessions, three radiologists with 5-25 years
      of clinical experience and 1 year of experience with synthetic 2D mammography
      read digital 2D and synthetic 2D images and assigned breast density categories
      according to the 5th edition of BI-RADS. Inter- and intrareader agreement was
      assessed for each BI-RADS density assessment and combined dense and nondense
      categories using percent agreement and Cohen kappa coefficient for consensus and
      all reads. RESULTS: A total of 309 patients met study inclusion criteria.
      Agreement between consensus BI-RADS density categories assigned for digital and
      synthetic 2D mammography was 80.3% (95% CI, 75.4-84.5%) with kappa = 0.73 (95%
      CI, 0.66-0.79). For combined dense and nondense categories, agreement reached
      91.9% (95% CI, 88.2-94.7%). For consensus readings, similar numbers of patients
      were shifted between nondense and dense categories (11 and 14, respectively) with
      the synthetic 2D compared with digital 2D mammography. Interreader differences
      were apparent; assignment to dense categories was greater with digital 2D
      mammography for reader 1 (odds ratio [OR], 1.26; p = 0.002), the same for reader
      2 (OR, 0.91; p = 0.262), and greater with synthetic 2D mammography for reader 3
      (OR, 0.86; p = 0.033). CONCLUSION: Overall, synthetic 2D mammography is
      comparable with digital 2D mammography in assessment of breast density, though
      there is some variability by reader. Practices can readily adopt synthetic 2D
      mammography without concern that it will affect density assessment and subsequent
      recommendations for supplemental screening.

PMID- 28504594
TI  - A Deep Dive into Asthma Transcriptomics. Lessons from U-BIOPRED.

PMID- 28504595
TI  - It's Bad-Really Bad-But Does it Matter? Medication Adherence in Chronic
      Obstructive Pulmonary Disease.

PMID- 28504596
TI  - Low Lung Function in Young Adult Life Is Associated with Early Mortality.

PMID- 28504597
TI  - Reply: Transpulmonary Pressure Meaning: Babel or Conceptual Evolution?

PMID- 28504598
TI  - Transpulmonary Pressure Meaning: Babel or Conceptual Evolution?

PMID- 28504599
TI  - Is Concomitant Use of Theophylline and Roflumilast Really Contraindicated?

PMID- 28504600
TI  - Adding Pedometers to Pulmonary Rehabilitation Did Not Result in Greater Physical
      Activity. An Important Answer, but What Was the Question?

PMID- 28504601
TI  - What's in a Number? Platelet Count Dynamics as a Novel Mediator of Acute
      Respiratory Distress Syndrome Survival.

PMID- 28504602
TI  - Eosinophils: Ancient Cells with New Roles in Chronic Lung Inflammation.

PMID- 28504603
TI  - Chronic Thromboembolic Pulmonary Hypertension: Part 1.

PMID- 28504604
TI  - Sputum Neutrophil Elastase as a Biomarker for Disease Activity in Bronchiectasis.

PMID- 28504606
TI  - Erratum: Objective Assessment of Adherence to Inhalers by Patients with Chronic
      Obstructive Pulmonary Disease.

PMID- 28504605
TI  - Learning Health Care System: Pragmatic Comparison of Crystalloid Choice in a
      Medical Intensive Care Unit.

PMID- 28504608
TI  - Interpretation of protein electrophoresis.

PMID- 28504607
TI  - Innate inflammatory gene expression profiling in potential brain-dead donors:
      detailed investigation of the effect of common corticosteroid therapy.
AB  - Our study aimed to assess the influence of common methylprednisolone therapy on
      innate inflammatory factors in potential brain-dead organ donors (BDDs). The
      study groups consisted of 50 potential BDDs who received 15 mg/kg/d
      methylprednisolone and 25 live organ donors (LDs) as control group. Innate
      immunity gene expression profiling was performed by RT-PCR array. Soluble serum
      cytokines and chemokines, complement components, heat shock protein 70 (HSP70)
      and high mobility group box-1 (HMGB1) were measured by ELISA. Surface expression
      of TLR2 and TLR4 were determined using flow cytometry. Gene expression profiling
      revealed up-regulation of TLRs 1, 2, 4, 5, 6, 7 and 8, MYD88, NF-kappaB, NF
      kappaB1A, IRAK1, STAT3, JAK2, TNF-alpha, IL-1beta, CD86 and CD14 in the BDD
      group. Remarkably, the serum levels of C-reactive protein and HSP70 were
      considerably higher in the BDD group. In addition, serum amounts of IL-1beta, IL
      6, TNF-alpha, HMGB1, HSP70, C3a and C5a, but not IL-8, sCD86 or monocyte
      chemoattractant protein-1, were significantly increased in the BDD group.
      Significant differences were observed in flow cytometry analysis of TLR2 and TLR4
      between the two groups. In summary, common methylprednisolone therapy in BDDs did
      not adequately reduce systemic inflammation, which could be due to inadequate
      doses or inefficient impact on other inflammatory-inducing pathways, for example
      oxidative stress or production of damage-associated molecules.

PMID- 28504609
TI  - Age and sex differences in serum adiponectin and its association with lipoprotein
      fractions.
AB  - Objective The correlation of adiponectin with cholesterol concentration of
      fractionated lipoproteins has not been well investigated. Methods This study
      included 174 subjects (79 men and 95 women) without diabetes. The medical record
      data were investigated retrospectively. The study subjects with adiponectin <8.3,
      > 8.3 but less 13.9, and >= 13.9 were classified into tertile groups: Groups A (
      n = 59), B ( n = 58) and C ( n = 57), respectively. Results In women, age and HDL
      C were higher in Group C than in Groups A and B, but BMI, TG, IDL-C and VLDL-C
      were lower in Group C than in Groups A and B. In men, BMI was lower in Group C
      than in Groups A and B, and HDL-C was higher in Group C than in Groups A and B.
      In multiple stepwise regression analysis, BMI and HDL-C were significantly
      correlated with adiponectin in whole, male and female subjects, but TG-rich
      lipoprotein cholesterol concentrations were not independently correlated.
      Conclusions HDL-C and BMI were independently correlated with adiponectin in non
      diabetic men and women. These results suggest that high adiponectin may play a
      role in the increased HDL-C concentrations, implicated in the reduction of
      cardiovascular disease risk, in non-diabetic subjects.

PMID- 28504610
TI  - Mind the gap: shortcomings of the osmotic gap and a possible solution.
AB  - Background Measured (MO) and calculated osmotic concentrations (CO) and the
      osmotic gap (OG) are commonly used in the investigation of electrolyte and volume
      disturbances as well as in cases of suspected volatile ingestion. Methods We
      compared 38 published formulae for CO with MO on a large data-set ( n = 9466) and
      adjusted the CO with the result of a Passing-Bablok regression procedure.
      Validation of this adjustment was performed with a separate data-set ( n = 2082).
      Results All but one of the CO formulae underestimate MO due to a proportional
      bias (slope 0.67 to 0.95) and the OG limits were therefore not applicable
      throughout the observed range. Using Passing-Bablok regression to adjust the CO:
      CO#3 = (2 * Na+urea+glucose-14.54)/0.93. After adjustment, the mean OG was 0.3
      mmol/L with a SD of 5.1 mmol/L across the measurement interval. The distribution
      of the OG could be fully explained by the analytical imprecision of the measured
      components. Conclusions Simple adjustment of the CO for the proportional
      underestimation of MO allows OG reference limits of approximately -10 to +10
      mmol/L to be used, even in the upper ranges of CO in patients with suspected
      volatile ingestion.

PMID- 28504611
TI  - Evolocumab and clinical outcomes in patients with cardiovascular disease.

PMID- 28504612
TI  - Changes in the albumin glycation site, plasma pentosidine and esRAGE
      concentrations before and after intensive diabetic treatment in patients with
      abnormally high glycated albumin levels.
AB  - Background We have reported that the blood glucose normalization treatment
      reduced the albumin glycation sites and the intensity of albumin AGE fluorescence
      in patients with abnormally high glycated albumin levels. To clarify the
      relationship between glycaemic control status and levels of glycated proteins and
      related markers, we studied the change of the markers of the DM patients with and
      without fatty liver, liver cirrhosis and dialysis before and after the intensive
      diabetic treatment. Methods Eight diabetic patients with abnormally high glycated
      albumin levels (no complications: 2, fatty liver: 3, liver cirrhosis: 2,
      dialysis: 1) were recruited. In the hypoglycaemic treatment for these patients,
      the HbA1c, glycated albumin, albumin AGE fluorescence, pentosidine, endogenous
      secretory receptors for AGE (esRAGE) and glycation sites of albumin were
      determined. Results Glycated albumin and HbA1c levels dropped after the
      treatment. Albumin glycation sites decreased in almost the same pattern,
      irrespective of the type of complications. The fluorescence intensity and
      pentosidine concentrations decreased significantly. However, post-treatment
      pentosidine concentrations were higher than the reference interval in all cases.
      Average esRAGE concentrations did not change and were lower than the reference
      interval. Conclusions Hypoglycaemic treatment reduced the glycated albumin
      levels, glycation sites of albumin and AGE concentrations but not esRAGE
      concentrations in diabetic patients with or without fatty liver, liver cirrhosis,
      and dialysis. Checking and maintaining low glycated albumin levels would prevent
      the formation of AGE and may be useful to prevent the onset or progression of
      diabetes complications.

PMID- 28504614
TI  - Quantifying the Effects of Water Temperature, Soap Volume, Lather Time, and
      Antimicrobial Soap as Variables in the Removal of Escherichia coli ATCC 11229
      from Hands.
AB  - The literature on hand washing, while extensive, often contains conflicting data,
      and key variables are only superficially studied or not studied at all. Some hand
      washing recommendations are made without scientific support, and agreement
      between recommendations is limited. The influence of key variables such as soap
      volume, lather time, water temperature, and product formulation on hand washing
      efficacy was investigated in the present study. Baseline conditions were 1 mL of
      a bland (nonantimicrobial) soap, a 5-s lather time, and 38 degrees C (100 degrees
      F) water temperature. A nonpathogenic strain of Escherichia coli (ATCC 11229) was
      the challenge microorganism. Twenty volunteers (10 men and 10 women) participated
      in the study, and each test condition had 20 replicates. An antimicrobial soap
      formulation (1% chloroxylenol) was not significantly more effective than the
      bland soap for removing E. coli under a variety of test conditions. Overall, the
      mean reduction was 1.94 log CFU (range, 1.83 to 2.10 log CFU) with the
      antimicrobial soap and 2.22 log CFU (range, 1.91 to 2.54 log CFU) with the bland
      soap. Overall, lather time significantly influenced efficacy in one scenario, in
      which a 0.5-log greater reduction was observed after 20 s with bland soap
      compared with the baseline wash (P = 0.020). Water temperature as high as 38
      degrees C (100 degrees F) and as low as 15 degrees C (60 degrees F) did not have
      a significant effect on the reduction of bacteria during hand washing; however,
      the energy usage differed between these temperatures. No significant differences
      were observed in mean log reductions experienced by men and women (both 2.08 log
      CFU; P = 0.988). A large part of the variability in the data was associated with
      the behaviors of the volunteers. Understanding what behaviors and human factors
      most influence hand washing may help researchers find techniques to optimize the
      effectiveness of hand washing.

PMID- 28504613
TI  - ChLpMab-23: Cancer-Specific Human-Mouse Chimeric Anti-Podoplanin Antibody
      Exhibits Antitumor Activity via Antibody-Dependent Cellular Cytotoxicity.
AB  - Podoplanin is expressed in many cancers, including oral cancers and brain tumors.
      The interaction between podoplanin and its receptor C-type lectin-like receptor 2
      (CLEC-2) has been reported to be involved in cancer metastasis and tumor
      malignancy. We previously established many monoclonal antibodies (mAbs) against
      human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23
      (IgG1, kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab.
      However, we have not shown the usefulness of LpMab-23 for antibody therapy
      against podoplanin-expressing cancers. In this study, we first determined the
      minimum epitope of LpMab-23 and revealed that Gly54-Leu64 peptide, especially
      Gly54, Thr55, Ser56, Glu57, Asp58, Arg59, Tyr60, and Leu64 of podoplanin, is a
      critical epitope of LpMab-23. We further produced human-mouse chimeric LpMab-23
      (chLpMab-23) and investigated whether chLpMab-23 exerts antibody-dependent
      cellular cytotoxicity (ADCC) and antitumor activity. In flow cytometry, chLpMab
      23 showed high sensitivity against a podoplanin-expressing glioblastoma cell
      line, LN319, and an oral cancer cell line, HSC-2. chLpMab-23 also showed ADCC
      activity against podoplanin-expressing CHO cells (CHO/podoplanin). In xenograft
      models with HSC-2 and CHO/podoplanin, chLpMab-23 exerts antitumor activity using
      human natural killer cells, indicating that chLpMab-23 could be useful for
      antibody therapy against podoplanin-expressing cancers.

PMID- 28504615
TI  - Perception Gaps on Food Additives among Various Groups in Korea: Food Experts,
      Teachers, Nutrition Teachers, Nongovernmental Organization Members, and General
      Consumers.
AB  - The purpose of this study was to determine the perceptions and information needs
      of food experts, teachers, nutrition teachers, members of nongovernmental
      organizations, and general consumers concerning food additives. Questions in a
      survey format included perceptions, information needs, and preferred
      communication channels. The survey was conducted both off-line and on-line via e
      mail and Google Drive in March 2015. The results indicated that most Korean
      consumers are concerned about the safety of using food additives in processed
      foods and do not recognize these additives as safe and useful materials as part
      of a modern diet. We also identified perception gaps among different groups
      regarding food additives. Nutrition teachers and members of nongovernmental
      organizations in Korea appeared to have a biased perception of food additives,
      which may cause general consumers to have a negative perception of food
      additives. The group of food experts did not have this bias. Governmental
      institutions must overcome the low confidence levels of various groups as an
      information provider about food additives. Based on the findings in this study,
      it will be possible to develop a strategy for risk communication about food
      additives for each group.

PMID- 28504616
TI  - Prevalence and Characterization of Campylobacter jejuni Isolated from Retail
      Chicken in Tianjin, China.
AB  - Campylobacter jejuni is an important foodborne pathogen worldwide; however, there
      is a lack of information on the prevalence and antibiotic-resistant profile of C.
      jejuni in the People's Republic of China. We determined the prevalence and
      characteristics of C. jejuni on the retail level in Tianjin, one of the five
      national central cities in China. A total of 227 samples of chicken wings, legs,
      and breasts were collected from supermarkets and wet markets; 42 of these samples
      were confirmed to be positive for Campylobacter contamination. The contamination
      rates of C. jejuni and other Campylobacter species were 13.7% (31 of 227 samples)
      and 5.7% (13 of 227 samples), respectively. A group of 31 C. jejuni isolates was
      subjected to antimicrobial susceptibility testing. All (100%) the selected
      isolates were resistant to ciprofloxacin and nalidixic acid; 77.4% were resistant
      to tetracycline, 67.7% to doxycycline, 35.5% to gentamicin, 25.8% to clindamycin
      and florfenicol, 19.4% to chloramphenicol, and 12.9% to erythromycin and
      azithromycin. A remarkably high proportion (41.9%) of multidrug-resistant
      isolates was identified. Multilocus sequence typing was conducted to study the
      population structure of the C. jejuni strains and their relationship to human
      isolates. The correlation between antimicrobial resistance traits and certain
      sequence types (STs) or clonal complexes was determined as well. A great genetic
      diversity of poultry isolates was identified, with 11 STs belonging to 6 clonal
      complexes and 11 singleton STs. The novel STs accounted for 40.9% (n = 9) of the
      22 STs. ST-21, ST-353, ST-354, ST-443, ST-607, and ST-828 complexes had been
      previously identified from human isolates. This study revealed an extensive level
      of antimicrobial resistance and genetic diversity in C. jejuni isolated from
      chicken products in Tianjin, highlighting the necessity of performing enforced
      interventions to reduce Campylobacter prevalence in China.

PMID- 28504619
TI  - Standard Area Diagrams for Aiding Severity Estimation: Scientometrics,
      Pathosystems, and Methodological Trends in the Last 25 Years.
AB  - Standard area diagrams (SAD) have long been used as a tool to aid the estimation
      of plant disease severity, an essential variable in phytopathometry. Formal
      validation of SAD was not considered prior to the early 1990s, when considerable
      effort began to be invested developing SAD and assessing their value for
      improving accuracy of estimates of disease severity in many pathosystems. Peer
      reviewed literature post-1990 was identified, selected, and cataloged in
      bibliographic software for further scrutiny and extraction of scientometric,
      pathosystem-related, and methodological-related data. In total, 105 studies (127
      SAD) were found and authored by 327 researchers from 10 countries, mainly from
      Brazil. The six most prolific authors published at least seven studies. The
      scientific impact of a SAD article, based on annual citations after publication
      year, was affected by disease significance, the journal's impact factor, and
      methodological innovation. The reviewed SAD encompassed 48 crops and 103 unique
      diseases across a range of plant organs. Severity was quantified largely by image
      analysis software such as QUANT, APS-Assess, or a LI-COR leaf area meter. The
      most typical SAD comprised five to eight black-and-white drawings of leaf
      diagrams, with severity increasing nonlinearly. However, there was a trend toward
      using true-color photographs or stylized representations in a range of color
      combinations and more linear (equally spaced) increments of severity. A two-step
      SAD validation approach was used in 78 of 105 studies for which linear regression
      was the preferred method but a trend toward using Lin's correlation concordance
      analysis and hypothesis tests to detect the effect of SAD on accuracy was
      apparent. Reliability measures, when obtained, mainly considered variation among
      rather than within raters. The implications of the findings and knowledge gaps
      are discussed. A list of best practices for designing and implementing SAD and a
      website called SADBank for hosting SAD research data are proposed.

PMID- 28504621
TI  - [A stroke mimic: hemichorea associated with non-ketotic hyperglycaemia].
AB  - An 85-year-old man with a history of diabetes was admitted with acute onset
      hemichorea. Laboratory findings confirmed poorly controlled diabetes. A brain
      computed tomography (CTC) revealed contralateral striatal hyperdensity. The
      findings were compatible with hyperglycaemia-induced hemichorea, and antidiabetic
      and symptomatic treatment was initiated. The symptoms remitted completely after
      six days, and a follow-up CTC showed partial resolution of the striatal changes.
      This case illustrates the importance of considering if hyperglycaemia is the
      cause of hemichorea, as early diagnosis and treatment yield an excellent
      prognosis.

PMID- 28504620
TI  - Identification of a distinctive phenotype for endocarditis-associated clonal
      complex 22 MRSA isolates with reduced vancomycin susceptibility.
AB  - PURPOSE: We previously identified an association between CC22 meticillin
      resistant Staphylococcus aureus (MRSA) bloodstream infection isolates with an
      elevated vancomycin MIC (V-MIC) in the susceptible range (1.5-2 mg l-1) and
      endocarditis. This study explores whether these isolates have a specific
      phenotype consistent with the clinical findings. METHODOLOGY: CC22 and CC30 MRSA
      isolates with high (1.5-2 mg l-1) and low (<=0.5 mg l-1) V-MICs were tested for
      fibrinogen and fibronectin binding, virulence in a Galleria mellonella
      caterpillar model, phenol soluble modulin production and accessory gene regulator
      (agr) expression. RESULTS: CC22 high V-MIC, but not CC30 high V-MIC isolates,
      showed sustained fibrinogen binding through a stationary growth phase and
      increased PSM production, specifically PSMalpha1, compared with respective low V
      MIC isolates. Expression was lower in both CC22 and CC30 high V-MIC isolates
      compared with respective low V-MIC isolates, although there was no associated
      reduction in virulence in the caterpillar model. CONCLUSIONS: The identification
      of a distinct phenotype for CC22 high V-MIC isolates supports the hypothesis that
      bacterial factors contribute to the mechanism underlying their association with
      endocarditis. Further study of these isolates could shed light on the molecular
      mechanism of endocarditis in humans.

PMID- 28504618
TI  - Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis
      and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice.
AB  - In this study, we investigated the effect of diet supplementation with sodium
      butyrate (5% w/w), a short-chain fatty acid produced by the intestinal
      microbiota, on metabolic parameters, body adiposity, hepatic and pancreatic lipid
      accumulation, beta cell function/mass as well as on the structure and function of
      the tight junction-mediated intestinal epithelial barrier in both normal and
      obese/prediabetic C57 mice fed a regular (control) or high-fat diet for 60 days,
      respectively. Butyrate treatment significantly inhibited all the high-fat-induced
      metabolic dysfunctions evaluated, i.e. significantly reduced the weight gain and
      body adiposity as well as the insulin resistant state, hyperglycemia and
      hyperinsulinemia, without changing food intake. In addition, high-fat-fed mice
      treated with this short-chain fatty acid displayed no compensatory hyperplasia of
      pancreatic beta cells nor marked hepatic steatosis as seen in prediabetic mice
      after high-fat diet only. Isolated pancreatic islets from high-fat-fed mice
      treated with butyrate showed improvement of the insulin secretion, which was
      associated with a significant decrease in lipid accumulation within the pancreas.
      Butyrate enhanced the intestinal epithelial barrier, as revealed by the FITC
      Dextran permeability assay, which was accompanied by a significant increase in
      the junctional content of the tight junction-associated claudin-1 in intestinal
      epithelia of jejunum, ileum, and colon of both control and high-fat mice. In
      conclusion, our results showed that diet supplementation with butyrate inhibits
      the deleterious effects of high-fat diet intake on metabolic parameters and
      structure/function of several tissues/organs associated with type 2 diabetes
      mellitus in a mouse model, suggesting a potential use of this short-chain fatty
      acid in the treatment of this endocrine-metabolic disorder. Impact statement
      Butyrate is a short-chain fatty acid produced by the intestinal microbiota
      through the fermentation of non-absorbable carbohydrates and proteins (e.g.
      fibers). Sodium butyrate incorporated into the diet displayed a protective action
      on metabolic, hepatic, pancreatic and intestinal alterations induced by high-fat
      diet in mice, resulting in significant inhibition of the development of a
      prediabetic state. Thus, our data suggest that butyrate may have a potential
      therapeutic use in the treatment of type 2 diabetes and related disorders.

PMID- 28504622
TI  - [Severe cervical kyphosis causing sudden inspiratory stridor].
AB  - An 85-year-old woman was brought to an accident and emergency department with
      breathing difficulties accompanied by inspiratory stridor. She was being treated
      for hypertension and severe osteoporosis which had caused thoracal and cervical
      fractures of the columna. Intubation was initiated as she desaturated and
      deteriorated despite maximum oxygen therapy. The intubation revealed a subglottic
      stenosis as a consequence of a recent osteoporotic fracture in the cervical
      columna. This represents a rare cause of respiratory failure as all other
      cardial, pulmonary and allergic aetiologies had been eliminated.

PMID- 28504617
TI  - Opportunities and challenges in the wider adoption of liver and interconnected
      microphysiological systems.
AB  - Liver disease represents a growing global health burden. The development of in
      vitro liver models which allow the study of disease and the prediction of
      metabolism and drug-induced liver injury in humans remains a challenge. The
      maintenance of functional primary hepatocytes cultures, the parenchymal cell of
      the liver, has historically been difficult with dedifferentiation and the
      consequent loss of hepatic function limiting utility. The desire for longer term
      functional liver cultures sparked the development of numerous systems, including
      collagen sandwiches, spheroids, micropatterned co-cultures and liver
      microphysiological systems. This review will focus on liver microphysiological
      systems, often referred to as liver-on-a-chip, and broaden to include platforms
      with interconnected microphysiological systems or multi-organ-chips. The
      interconnection of microphysiological systems presents the opportunity to explore
      system level effects, investigate organ cross talk, and address questions which
      were previously the preserve of animal experimentation. As a field,
      microphysiological systems have reached a level of maturity suitable for
      commercialization and consequent evaluation by a wider community of users, in
      academia and the pharmaceutical industry. Here scientific, operational, and
      organizational considerations relevant to the wider adoption of
      microphysiological systems will be discussed. Applications in which
      microphysiological systems might offer unique scientific insights or enable
      studies currently feasible only with animal models are described, and challenges
      which might be addressed to enable wider adoption of the technologies are
      highlighted. A path forward which envisions the development of microphysiological
      systems in partnerships between academia, vendors and industry, is proposed.
      Impact statement Microphysiological systems are in vitro models of human tissues
      and organs. These systems have advanced rapidly in recent years and are now being
      commercialized. To achieve wide adoption in the biological and pharmaceutical
      research communities, microphysiological systems must provide unique insights
      which translate to humans. This will be achieved by identifying key applications
      and making microphysiological systems intuitive to use.

PMID- 28504623
TI  - [Family psychoeducation for affective disorders].
AB  - The aim of this article was to examine the evidence of family psychoeducation
      (FPE) for affective disorders. Evidence indicates that FPE can be an effective
      supplement to the standard treatment of patients with affective disorders. FPE
      can effectively reduce the patients' risk of relapse and reduce the burden
      experienced by the relatives. However, current studies are very heterogeneous and
      therefore difficult to compare. Up to this point the evidence regarding the
      effect of FPE on unipolar depression is still very sparse and further research is
      needed.

PMID- 28504624
TI  - [Damage control surgery in patients with abdominal sepsis].
AB  - Damage control surgery (DCS) and resuscitation has improved the survival of
      trauma patients with decompensated physiology. In recent years, the principles of
      DCS have been used in the treatment of patients with abdominal sepsis, despite
      the fact that only a minimum of evidence exists. The aim is to optimize the
      physiology prior to definitive surgery. This implies a primary decontaminating
      surgical procedure with temporary abdominal closure without restoration of the
      intestinal continuity and avoidance of stoma formation in order to reduce time in
      the operating theatre.

PMID- 28504625
TI  - ?

PMID- 28504626
TI  - [Danish malaria research from the frail beginning to internationally acknowledged
      research].
AB  - Malaria - and particularly the disease caused by Plasmodium falciparum - remains
      a direct as well as indirect cause of poverty and immense human suffering.
      Research is imperative to alleviate this situation and to control and eventually
      eradicate the disease. Since the mid-1970s, Danish scientists have contributed
      increasingly to this effort by publishing more than 700 scientific papers and by
      training about 60 highly skilled malaria researchers. The efforts which continue
      to be thoroughly dependent on extensive external funding and public goodwill are
      briefly reviewed in this article.

PMID- 28504627
TI  - [High-isolation preparedness for very contagious and potential severely ill
      patients].
AB  - Ten and seven years ago respectively, the two high-isolation units in Denmark
      became prepared to receive highly contagious and potential severely ill patients.
      The units are located in the departments of infectious diseases in Hvidovre
      Hospital and Aarhus University Hospital. Both departments had little experience
      until the Ebola outbreak in West Africa, 2013-2015. Altogether, 15 possible Ebola
      patients were examined in the two departments, but the diagnosis was ruled out
      for all of them. Besides, a few possible candidates for Middle East respiratory
      syndrome patients were examined. Always being prepared in a busy clinical
      everyday environment is a challenge, and it takes regular training and exercises
      involving all personnel.

PMID- 28504628
TI  - [The current global tuberculosis state].
AB  - Despite an increase in the total number of tuberculosis (TB) patients globally,
      positive trends in reduction of prevalence and mortality are observed. However,
      high numbers of drug-resistant cases are threatening this trend. Multidrug
      resistant and extensively resistant cases constitute an increasing challenge in
      many parts of the world also within the European region - especially in former
      Sovjet Republic nations. Point-of-care test systems potentially replacing
      microscopy and urine antigen detection systems are currently launched in many TB
      high endemic countries improving TB detection rates. However, the effect on key
      indicators like mortality is still waiting to break through.

PMID- 28504629
TI  - [Acute malnutrition in children].
AB  - The prevalence of malnutrition has declined significantly over the last 30 years.
      Despite this, malnutrition remains a major cause of illness and death among
      children worldwide, particularly in low- and medium-income countries. Marasmus
      and kwashiorkor are the most life-threatening forms of malnutrition. Treatment
      protocols enable effective treatment, but only a minority of malnourished
      children have access to treatment. Furthermore, treating children with
      complicated malnutrition requiring hospitalization remains a clinical challenge.

PMID- 28504630
TI  - [Global differences in causes and diagnostics of cardio-metabolic diseases].
AB  - Cardio-metabolic diseases (CMDs) such as obesity, type 2 diabetes (T2D) and
      hypertension are now highly prevalent throughout low- and middle-income
      countries, even though half of the T2D cases cannot be explained by obesity. Non
      obese T2D individuals may have been exposed to foetal programming and/or be
      genetically susceptible to abdominal obesity. There is evidence for ethnic
      specific risks for cardiometabolic disease. This calls for expanding research
      collaboration with so-called South partners in order to qualify decision making
      on diagnosis and prevention of CMDs at global level.

PMID- 28504631
TI  - [Climate change, floods and health intervention].
AB  - Climate change and variability are considered some of the biggest threats to
      human health in the 21st century. Extreme weather events such as floods and
      storms are examples of natural hazards resulting in highest number of disasters
      and with considerable mortality and morbidity among vulnerable communities. A
      coordinated, well-planned management of health interventions must be taken for
      timely action in the response, recovery, prevention and preparedness phases of
      disasters. Roles and responsibilities of international as well as national
      organizations and authorities are discussed.

PMID- 28504632
TI  - [Medical tourism and its implications for patients and hospital services
      throughout the world].
AB  - This article provides a snapshot of global medical tourism and its positive and
      negative implications for healthcare around the world presented through selected
      examples. Medical tourism is an old phenomenon which has seen a rapid increase
      due to global technological advances thus enabling people to receive treatment
      anywhere in the world, often combined with a tropical vacation. Treatments are of
      a non-acute, voluntary nature and are driven largely by high prices and long
      waiting lists at the home countries and low prices and high service quality at
      the destination country.

PMID- 28504633
TI  - [Tick-borne infections in Denmark].
AB  - The castor bean tick, Ixodes ricinus, is common in woodlands in most of Denmark.
      Besides Borrelia burgdorferi, it can harbour a number of pathogenic
      microorganisms such as tick-borne encephalitis virus, Anaplasma phagocytophilum,
      Rickettsia helvetica, Francisella tularensis, Candidatus Neoehrlichia mikurensis,
      Bartonella spp., Borrelia miyamotoi and Babesia spp. These tick-borne infections
      should be a differential diagnostic consideration during the tick season in
      Denmark. We review the distribution, clinical manifestations, diagnosis and
      treatment of these microorganisms.

PMID- 28504634
TI  - [A burned-out seminoma lymph node metastasis to the neck of a patient treated for
      colon cancer].
AB  - The incidence of metastases to the neck in testicular cancer is 4-15%, and in 5%
      of these cases the metastasis is the only symptom. We present a 57-year-old
      asymptomatic male, who had previously been treated for colon cancer. A routine
      PET-CT showed enlarged lymph nodes in the retroperitoneum and at the neck. A core
      needle biopsy from the lymph node at the neck contained malignant cells, but not
      from colon cancer. The lymph node was extirpated, and pathological analysis
      proved it to be a metastasis from a testicular seminoma. A burned-out seminoma
      was subsequently found in the patient's right testicle.

PMID- 28504635
TI  - [Favism after ingestion of fava beans in a three-year-old child with glucose-6
      phosphate dehydrogenase deficiency].
AB  - A three-year-old Syrian boy was hospitalized with symptoms of acute haemolytic
      anaemia after ingestion of fava beans. He was stabilized by blood transfusion,
      and genetic examination revealed glucose-6-phosphate dehydrogenase (G6PD)
      deficiency. Oxidative stress, e.g. ingestion of fava beans, can induce acute
      haemolytic anaemia in affected individuals. Approximately 400 million people
      worldwide suffer from G6PD deficiency. The prevalence is high in African,
      Mediterranean and Middle East countries. Due to increased immigration, we might
      expect the condition to occur more often in Danish healthcare.

PMID- 28504636
TI  - [Eggs do not increase the risk of cardiovascular disease and can be safely
      consumed].
AB  - Eggs are nutrient dense, rich in essential amino- and fatty acids, and the most
      cholesterol containing food. Based on observational studies the consumption of
      eggs has since the 1970's been claimed to increase the risk of cardiovascular
      disease (CVD). Intervention studies on intake of eggs and plasma cholesterol do
      however not support causality. The higher incidence of CVD in egg eaters is more
      likely to be caused by the clustering of other CVD risk factors. Up to seven eggs
      per week can safely be consumed but in patients with CVD or diabetes only with
      special emphasis on a prudent diet and proper medical treatment.

PMID- 28504637
TI  - [Evidence of the effect of psychodynamic psychotherapy].
AB  - Evidence of the effect of psychodynamic psychotherapy (PDT) has been called into
      question. Thus, an updated review of the effect of short-term and long-term PDT
      (STPP and LTPP) for anxiety, depression and personality disorders seems
      necessary. A systematic search of randomized controlled studies of PDT published
      from January 2000 to May 2016 was conducted, and we found 57 single studies and
      13 meta-analyses fulfilling the criteria for inclusion. The studies show that PDT
      has therapeutic efficacy and effectiveness matching other forms of psychotherapy.
      LTPP shows better effect than STPP in the treatment of complex psychiatric
      disorders and long-term depression.

PMID- 28504638
TI  - Catecholaminergic challenge uncovers distinct Pavlovian and instrumental
      mechanisms of motivated (in)action.
AB  - Catecholamines modulate the impact of motivational cues on action. Such
      motivational biases have been proposed to reflect cue-based, 'Pavlovian' effects.
      Here, we assess whether motivational biases may also arise from asymmetrical
      instrumental learning of active and passive responses following reward and
      punishment outcomes. We present a novel paradigm, allowing us to disentangle the
      impact of reward and punishment on instrumental learning from Pavlovian response
      biasing. Computational analyses showed that motivational biases reflect both
      Pavlovian and instrumental effects: reward and punishment cues promoted
      generalized (in)action in a Pavlovian manner, whereas outcomes enhanced
      instrumental (un)learning of chosen actions. These cue- and outcome-based biases
      were altered independently by the catecholamine enhancer melthylphenidate.
      Methylphenidate's effect varied across individuals with a putative proxy of
      baseline dopamine synthesis capacity, working memory span. Our study uncovers two
      distinct mechanisms by which motivation impacts behaviour, and helps refine
      current models of catecholaminergic modulation of motivated action.

PMID- 28504639
TI  - Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a
      two-head-bound state on microtubules.
AB  - The detailed basis of walking by dimeric molecules of kinesin along microtubules
      has remained unclear, partly because available structural methods have been
      unable to capture microtubule-bound intermediates of this process. Utilizing
      novel electron cryomicroscopy methods, we solved structures of microtubule
      attached, dimeric kinesin bound to an ATP analog. We find that under these
      conditions, the kinesin dimer can attach to the microtubule with either one or
      two motor domains, and we present sub-nanometer resolution reconstructions of
      both states. The former structure reveals a novel kinesin conformation that
      revises the current understanding of how ATP binding is coupled to forward
      stepping of the motor. The latter structure indicates how tension between the two
      motor domains keeps their cycles out of phase in order to stimulate directional
      motility. The methods presented here pave the way for future structural studies
      of a variety of challenging macromolecules that bind to microtubules and other
      filaments.

PMID- 28504640
TI  - The Sec61 translocon limits IRE1alpha signaling during the unfolded protein
      response.
AB  - IRE1alpha is an endoplasmic reticulum (ER) localized endonuclease activated by
      misfolded proteins in the ER. Previously, we demonstrated that IRE1alpha forms a
      complex with the Sec61 translocon, to which its substrate XBP1u mRNA is recruited
      for cleavage during ER stress (Plumb et al., 2015). Here, we probe IRE1alpha
      complexes in cells with blue native PAGE immunoblotting. We find that IRE1alpha
      forms a hetero-oligomeric complex with the Sec61 translocon that is activated
      upon ER stress with little change in the complex. In addition, IRE1alpha
      oligomerization, activation, and inactivation during ER stress are regulated by
      Sec61. Loss of the IRE1alpha-Sec61 translocon interaction as well as severe ER
      stress conditions causes IRE1alpha to form higher-order oligomers that exhibit
      continuous activation and extended cleavage of XBP1u mRNA. Thus, we propose that
      the Sec61-IRE1alpha complex defines the extent of IRE1alpha activity and may
      determine cell fate decisions during ER stress conditions.

PMID- 28504642
TI  - Ion recombination correction factor in scanned light-ion beams for absolute dose
      measurement using plane-parallel ionisation chambers.
AB  - Based on international reference dosimetry protocols for light-ion beams, a
      correction factor (k s) has to be applied to the response of a plane-parallel
      ionisation chamber, to account for recombination of negative and positive charges
      in its air cavity before these charges can be collected on the electrodes. In
      this work, k s for IBA PPC40 Roos-type chambers is investigated in four scanned
      light-ion beams (proton, helium, carbon and oxygen). To take into account the
      high dose-rates used with scanned beams and LET-values, experimental results are
      compared to a model combining two theories. One theory, developed by Jaffe,
      describes the variation of k s with the ionization density within the ion track
      (initial recombination) and the other theory, developed by Boag, describes the
      variation of k s with the dose rate (volume recombination). Excellent agreement
      is found between experimental and theoretical k s-values. All results confirm
      that k s cannot be neglected. The solution to minimise k s is to use the
      ionisation chamber at high voltage. However, one must be aware that charge
      multiplication may complicate the interpretation of the measurement. For the
      chamber tested, it was found that a voltage of 300 V can be used without further
      complication. As the initial recombination has a logarithmic variation as a
      function of 1/V, the two-voltage method is not applicable to these scanned beams.

PMID- 28504643
TI  - Exploiting neurovascular coupling: a Bayesian sequential Monte Carlo approach
      applied to simulated EEG fNIRS data.
AB  - OBJECTIVE: Electrical and hemodynamic brain activity are linked through the
      neurovascular coupling process and they can be simultaneously measured through
      integration of electroencephalography (EEG) and functional near-infrared
      spectroscopy (fNIRS). Thanks to the lack of electro-optical interference, the two
      procedures can be easily combined and, whereas EEG provides electrophysiological
      information, fNIRS can provide measurements of two hemodynamic variables, such as
      oxygenated and deoxygenated hemoglobin. A Bayesian sequential Monte Carlo
      approach (particle filter, PF) was applied to simulated recordings of electrical
      and neurovascular mediated hemodynamic activity, and the advantages of a unified
      framework were shown. APPROACH: Multiple neural activities and hemodynamic
      responses were simulated in the primary motor cortex of a subject brain. EEG and
      fNIRS recordings were obtained by means of forward models of volume conduction
      and light propagation through the head. A state space model of combined EEG and
      fNIRS data was built and its dynamic evolution was estimated through a Bayesian
      sequential Monte Carlo approach (PF). MAIN RESULTS: We showed the feasibility of
      the procedure and the improvements in both electrical and hemodynamic brain
      activity reconstruction when using the PF on combined EEG and fNIRS measurements.
      SIGNIFICANCE: The investigated procedure allows one to combine the information
      provided by the two methodologies, and, by taking advantage of a physical model
      of the coupling between electrical and hemodynamic response, to obtain a better
      estimate of brain activity evolution. Despite the high computational demand,
      application of such an approach to in vivo recordings could fully exploit the
      advantages of this combined brain imaging technology.

PMID- 28504644
TI  - Direct reconstruction of parametric images for brain PET with event-by-event
      motion correction: evaluation in two tracers across count levels.
AB  - Parametric images for dynamic positron emission tomography (PET) are typically
      generated by an indirect method, i.e. reconstructing a time series of emission
      images, then fitting a kinetic model to each voxel time activity curve.
      Alternatively, 'direct reconstruction', incorporates the kinetic model into the
      reconstruction algorithm itself, directly producing parametric images from
      projection data. Direct reconstruction has been shown to achieve parametric
      images with lower standard error than the indirect method. Here, we present
      direct reconstruction for brain PET using event-by-event motion correction of
      list-mode data, applied to two tracers. Event-by-event motion correction was
      implemented for direct reconstruction in the Parametric Motion-compensation OSEM
      List-mode Algorithm for Resolution-recovery reconstruction. The direct
      implementation was tested on simulated and human datasets with tracers [11C]AFM
      (serotonin transporter) and [11C]UCB-J (synaptic density), which follow the 1
      tissue compartment model. Rigid head motion was tracked with the Vicra system.
      Parametric images of K 1 and distribution volume (V T  =  K 1/k 2) were compared
      to those generated by the indirect method by regional coefficient of variation
      (CoV). Performance across count levels was assessed using sub-sampled datasets.
      For simulated and real datasets at high counts, the two methods estimated K 1 and
      V T with comparable accuracy. At lower count levels, the direct method was
      substantially more robust to outliers than the indirect method. Compared to the
      indirect method, direct reconstruction reduced regional K 1 CoV by 35-48%
      (simulated dataset), 39-43% ([11C]AFM dataset) and 30-36% ([11C]UCB-J dataset)
      across count levels (averaged over regions at matched iteration); V T CoV was
      reduced by 51-58%, 54-60% and 30-46%, respectively. Motion correction played an
      important role in the dataset with larger motion: correction increased regional V
      T by 51% on average in the [11C]UCB-J dataset. Direct reconstruction of dynamic
      brain PET with event-by-event motion correction is achievable and dramatically
      more robust to noise in V T images than the indirect method.

PMID- 28504641
TI  - Helical jackknives control the gates of the double-pore K+ uptake system KtrAB.
AB  - Ion channel gating is essential for cellular homeostasis and is tightly
      controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK
      domains regulate ion fluxes. Until now, a single regulatory mechanism has been
      proposed for all RCK-regulated channels, involving signal transduction from the
      RCK domain to the gating area. Here, we present an inactive ADP-bound structure
      of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy,
      which, combined with EPR spectroscopy and molecular dynamics simulations,
      uncovers a novel regulatory mechanism for ligand-induced action at a distance.
      Exchange of activating ATP to inactivating ADP triggers short helical segments in
      the K+-translocating KtrB dimer to organize into two long helices that penetrate
      deeply into the regulatory RCK domains, thus connecting nucleotide-binding sites
      and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial
      pathogenicity factors, the discovery of this functionally relevant inactive
      conformation may advance structure-guided drug development.

PMID- 28504645
TI  - Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for
      epilepsy.
AB  - Approximately 30% of epilepsy patients do not respond to antiepileptic drugs,
      representing an unmet medical need. There is evidence that neuroinflammation
      plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1
      (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic
      injuries, and its activation contributes to seizure generation in animal models.
      However, further work is required to understand the role of HMGB1 and its
      isoforms in epileptogenesis and drug resistance. Using a combination of animal
      models and sera from clinically well-characterized patients, we have demonstrated
      that there are dynamic changes in HMGB1 isoforms in the brain and blood of
      animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform
      progressively increased in blood before epilepsy onset and prospectively
      identified animals that developed the disease. Consistent with animal data, we
      observed early expression of disulfide HMGB1 in patients with newly diagnosed
      epilepsy, and its persistence was associated with subsequent seizures. In
      contrast with patients with well-controlled epilepsy, patients with chronic, drug
      refractory epilepsy persistently expressed the acetylated, disulfide HMGB1
      isoforms. Moreover, treatment of animals with antiinflammatory drugs during
      epileptogenesis prevented both disease progression and blood increase in HMGB1
      isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for
      epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation
      in larger-scale prospective studies.

PMID- 28504646
TI  - The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged
      neutrophils during bacterial infection.
AB  - Protective responses against pathogens require a rapid mobilization of resting
      neutrophils and the timely removal of activated ones. Neutrophils are
      exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan
      of pathogen-engaged neutrophils is regulated differently from that in the
      circulating steady-state pool. Here, we have found that under homeostatic
      conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates
      apoptosis and the numbers of activated infiltrating murine neutrophils but not
      neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased
      apoptosis and enhanced accumulation at the infection site. In the context of
      myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment
      protected mice against lethal soft tissue infection with Streptococcus pyogenes
      and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed
      that decreased apoptosis of TTP-deficient neutrophils was specifically associated
      with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other
      antiapoptotic B cell leukemia/lymphoma 2 (Bcl2) family members. Higher Mcl1
      expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The
      low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to
      that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that
      posttranscriptional gene regulation by TTP schedules the termination of the
      antimicrobial engagement of neutrophils. The balancing role of TTP comes at the
      cost of an increased risk of bacterial infections.

PMID- 28504648
TI  - The SO(H)L(H) "O" drivers of oocyte growth and survival but not meiosis I.
AB  - The spermatogenesis/oogenesis helix-loop-helix (SOHLH) proteins SOHLH1 and SOHLH2
      play important roles in male and female reproduction. Although previous studies
      indicate that these transcriptional regulators are expressed in and have in vivo
      roles in postnatal ovaries, their expression and function in the embryonic ovary
      remain largely unknown. Because oocyte differentiation is tightly coupled with
      the onset of meiosis, it is of significant interest to determine how early oocyte
      transcription factors regulate these two processes. In this issue of the JCI,
      Shin and colleagues report that SOHLH1 and SOHLH2 demonstrate distinct expression
      patterns in the embryonic ovary and interact with each other and other oocyte
      specific transcription factors to regulate oocyte differentiation. Interestingly,
      even though there is a rapid loss of oocytes postnatally in ovaries with combined
      loss of Sohlh1 and Sohlh2, meiosis is not affected and proceeds normally.

PMID- 28504647
TI  - Identification of a nucleoside analog active against adenosine kinase-expressing
      plasma cell malignancies.
AB  - Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell
      origin with plasmacytic differentiation. Here, we report the identification of a
      highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is
      a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other
      lymphoma cell lines tested. We developed and performed resistome analysis, an
      unbiased approach based on RNA sequencing of resistant subclones, to discover the
      molecular mechanisms of sensitivity. We found different adenosine kinase
      inactivating (ADK-inactivating) alterations in all resistant clones and
      determined that ADK is required to phosphorylate and activate 6-ETI. Further, we
      observed that 6-ETI induces ATP depletion and cell death accompanied by S phase
      arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK
      served as a biomarker approach to identify 6-ETI-sensitive tumors, which we
      documented for other lymphoid malignancies with plasmacytic features. Notably,
      multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM
      cell lines and primary specimens and had a robust antitumor effect in a
      disseminated MM mouse model. Several nucleoside analogs are effective in treating
      leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment
      of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.

PMID- 28504649
TI  - Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth.
AB  - Targeted cancer therapies, which act on specific cancer-associated molecular
      targets, are predominantly inhibitors of oncogenic kinases. While these drugs
      have achieved some clinical success, the inactivation of kinase signaling via
      stimulation of endogenous phosphatases has received minimal attention as an
      alternative targeted approach. Here, we have demonstrated that activation of the
      tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple
      oncogenic signaling proteins, is a promising therapeutic approach for the
      treatment of cancers. Our group previously developed a series of orally
      bioavailable small molecule activators of PP2A, termed SMAPs. We now report that
      SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse
      xenografts and transgenic models. Mechanistically, we found that SMAPs act by
      binding to the PP2A Aalpha scaffold subunit to drive conformational changes in
      PP2A. These results show that PP2A can be activated in cancer cells to inhibit
      proliferation. Our strategy of reactivating endogenous PP2A may be applicable to
      the treatment of other diseases and represents an advancement toward the
      development of small molecule activators of tumor suppressor proteins.

PMID- 28504652
TI  - A SMAP in the face for cancer.
AB  - Observed deficits in protein phosphatase 2A (PP2A) function in a variety of human
      cancers have stimulated drug discovery efforts aimed at restoring PP2A function
      to inhibit tumor growth. Work published by Sangodkar et al. in this issue of the
      JCI describes the characterization of orally available small molecule activators
      of PP2A (SMAPs). These SMAPs attenuated mitogenic signaling and triggered
      apoptosis in KRAS-mutant lung cancer cells and inhibited tumor growth in murine
      models. Tumors with mutations in the SMAP-binding site of the PP2A A subunit
      displayed resistance to SMAPs. Future studies that identify the PP2A-regulated
      events targeted by SMAPs should guide critical decisions about which cancers
      might be best treated with these molecules. This study provides encouraging
      evidence in favor of SMAPs as potential anticancer drugs.

PMID- 28504650
TI  - Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated
      thrombocytosis and atherogenesis in diabetes.
AB  - Platelets play a critical role in atherogenesis and thrombosis-mediated
      myocardial ischemia, processes that are accelerated in diabetes. Whether
      hyperglycemia promotes platelet production and whether enhanced platelet
      production contributes to enhanced atherothrombosis remains unknown. Here we
      found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding
      proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end
      products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL
      6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis. IL-6
      acts on hepatocytes to enhance the production of thrombopoietin, which in turn
      interacts with its cognate receptor c-MPL on megakaryocytes and bone marrow
      progenitor cells to promote their expansion and proliferation, resulting in
      reticulated thrombocytosis. Lowering blood glucose using a sodium-glucose
      cotransporter 2 inhibitor (dapagliflozin), depleting neutrophils or Kupffer
      cells, or inhibiting S100A8/A9 binding to RAGE (using paquinimod), all reduced
      diabetes-induced thrombocytosis. Inhibiting S100A8/A9 also decreased
      atherogenesis in diabetic mice. Finally, we found that patients with type 2
      diabetes have reticulated thrombocytosis that correlates with glycated hemoglobin
      as well as increased plasma S100A8/A9 levels. These studies provide insights into
      the mechanisms that regulate platelet production and may aid in the development
      of strategies to improve on current antiplatelet therapies and to reduce
      cardiovascular disease risk in diabetes.

PMID- 28504651
TI  - Aging and the immune response to organ transplantation.
AB  - An increasing number of older people receive organ transplants for various end
      stage conditions. Although organ transplantation is an effective therapy for
      older patients (i.e., older than 65 years of age), such as in end-stage renal
      disease, this therapy has not been optimized for older patients because of our
      lack of understanding of the effect of aging and the immune response to organ
      transplantation. Here, we provide an overview of the impact of aging on both the
      allograft and the recipient and its effect on the immune response to organ
      transplantation. We describe what has been determined to date, discuss existing
      gaps in our knowledge, and make suggestions on necessary future studies to
      optimize organ transplantation for older people.

PMID- 28504653
TI  - Metabolic shifts in residual breast cancer drive tumor recurrence.
AB  - Tumor recurrence is the leading cause of breast cancer-related death. Recurrences
      are largely driven by cancer cells that survive therapeutic intervention. This
      poorly understood population is referred to as minimal residual disease. Here,
      using mouse models that faithfully recapitulate human disease together with
      organoid cultures, we have demonstrated that residual cells acquire a
      transcriptionally distinct state from normal epithelium and primary tumors. Gene
      expression changes and functional characterization revealed altered lipid
      metabolism and elevated ROS as hallmarks of the cells that survive tumor
      regression. These residual cells exhibited increased oxidative DNA damage,
      potentiating the acquisition of somatic mutations during hormonal-induced
      expansion of the mammary cell population. Inhibition of either cellular fatty
      acid synthesis or fatty acid transport into mitochondria reduced cellular ROS
      levels and DNA damage, linking these features to lipid metabolism. Direct
      perturbation of these hallmarks in vivo, either by scavenging ROS or by halting
      the cyclic mammary cell population expansion, attenuated tumor recurrence.
      Finally, these observations were mirrored in transcriptomic and histological
      signatures of residual cancer cells from neoadjuvant-treated breast cancer
      patients. These results highlight the potential of lipid metabolism and ROS as
      therapeutic targets for reducing tumor recurrence in breast cancer patients.

PMID- 28504654
TI  - Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to
      thrombocytosis and platelet reactivity.
AB  - Diabetes mellitus is associated with an increased risk for cardiovascular
      disease, but the link between hyperglycemia and atherothrombotic disease is not
      completely understood. Patients with diabetes often show hyporesponsiveness to
      antiplatelet therapies, and it has been suggested that hyperreactive reticulated
      platelets underlie this altered therapeutic response. In this issue of the JCI,
      Kraakman et al. uncover a previously unknown link between hyperglycemia and
      enhanced platelet production and reactivity. The authors demonstrate that high
      blood glucose levels trigger neutrophil release of S100 calcium-binding protein
      A8/A9 (S100A8/A9), which binds to the receptor for advanced glycation end
      products (RAGE) on Kupffer cells, ultimately leading to increased thrombopoietin
      (TPO) production in the liver. TPO causes megakaryocyte proliferation and
      increased platelet production. This study demonstrates the importance of glycemic
      control and identifies potential therapeutic targets in the normalization of
      platelet numbers and function in diabetes.

PMID- 28504655
TI  - Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without
      affecting meiosis I.
AB  - Following migration of primordial germ cells to the genital ridge, oogonia
      undergo several rounds of mitotic division and enter meiosis at approximately
      E13.5. Most oocytes arrest in the dictyate (diplotene) stage of meiosis circa
      E18.5. The genes necessary to drive oocyte differentiation in parallel with
      meiosis are unknown. Here, we have investigated whether expression of
      spermatogenesis and oogenesis bHLH transcription factor 1 (Sohlh1) and Sohlh2
      coordinates oocyte differentiation within the embryonic ovary. We found that
      SOHLH2 protein was expressed in the mouse germline as early as E12.5 and preceded
      SOHLH1 protein expression, which occurred circa E15.5. SOHLH1 protein appearance
      at E15.5 correlated with SOHLH2 translocation from the cytoplasm into the nucleus
      and was dependent on SOHLH1 expression. NOBOX oogenesis homeobox (NOBOX) and LIM
      homeobox protein 8 (LHX8), two important regulators of postnatal oogenesis, were
      coexpressed with SOHLH1. Single deficiency of Sohlh1 or Sohlh2 disrupted the
      expression of LHX8 and NOBOX in the embryonic gonad without affecting meiosis.
      Sohlh1-KO infertility was rescued by conditional expression of the Sohlh1
      transgene after the onset of meiosis. However, Sohlh1 or Sohlh2 transgene
      expression could not rescue Sohlh2-KO infertility due to a lack of Sohlh1 or
      Sohlh2 expression in rescued mice. Our results indicate that Sohlh1 and Sohlh2
      are essential regulators of oocyte differentiation but do not affect meiosis I.

PMID- 28504656
TI  - Effect of IL-1beta, TNF-alpha and IGF-1 on trans-endothelial passage of synthetic
      vectors through an in vitro vascular endothelial barrier of striated muscle.
AB  - When administrated in the blood circulation, plasmid DNA (pDNA) complexed with
      synthetic vectors must pass through a vascular endothelium to transfect
      underlying tissues. Under inflammatory condition, cytokines can modify the
      endothelium integrity. Here, the trans-endothelial passage (TEP) of DNA complexes
      including polyplexes, lipoplexes and lipopolyplexes was investigated in the
      presence of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)
      or insulin-like growth factor-1 (IGF-1). The experiments were performed by using
      an in vitro model comprising a monolayer of mouse cardiac endothelial cells
      (MCEC) seeded on a trans-well insert and the transfection of C2C12 myoblasts
      cultured on the lower chamber as read out of TEP. We report that polyplexes made
      with a histidinylated derivative of lPEI (His-lPEI) exhibit the highest capacity
      (10.5 MUg cm-2 h versus 0.324 MUg cm-2 h) to cross TNF-alpha-induced inflamed
      endothelium model, but this positive effect is counterbalanced by the presence of
      IL-1beta. His-lPEI polyplex TEP is also increased in the presence of IGF-1 (2.58
      MUg cm-2 h). TEP of lipid-based DNA complexes including lipoplexes and
      lipopolyplexes was lowest compared with polymer-based DNA complexes. Overall, the
      results indicate that under inflammation, His-lPEI polyplexes have a good profile
      to cross a vascular endothelium of striated muscle with low cytotoxicity and high
      transfection efficiency of C2C12 myoblasts. These data provide insights
      concerning the endothelial passage of vectors in inflammatory conditions and can
      serve as a basis towards in vivo studies.

PMID- 28504657
TI  - Engineering liposomal nanoparticles for targeted gene therapy.
AB  - Recent mechanistic studies have attempted to deepen our understanding of the
      process by which liposome-mediated delivery of genetic material occurs.
      Understanding the interactions between lipid nanoparticles and cells is still
      largely elusive. Liposome-mediated delivery of genetic material faces systemic
      obstacles alongside entry into the cell, endosomal escape, lysosomal degradation
      and nuclear uptake. Rational design approaches for targeted delivery have been
      developed to reduce off-target effects and enhance transfection. These
      strategies, which have included the modification of lipid nanoparticles with
      target-specific ligands to enhance intracellular uptake, have shown significant
      promise at the proof-of-concept stage. Control of physical and chemical
      specifications of liposome composition, which includes lipid-to-DNA charge, size,
      presence of ester bonds, chain length and nature of ligand complexation, is
      integral to the performance of targeted liposomes as genetic delivery agents.
      Clinical advances are expected to rely on such systems in the therapeutic
      application of liposome nanoparticle-based gene therapy. Here, we discuss the
      latest breakthroughs in the development of targeted liposome-based agents for the
      delivery of genetic material, paying particular attention to new ligand and
      cationic lipid design as well as recent in vivo advances.

PMID- 28504658
TI  - Cure SMA and our patient community celebrate the first approved drug for SMA.
AB  - Cure SMA is dedicated to the treatment and cure of spinal muscular atrophy (SMA)
      a disease affecting motor neurons, that robs patients of their ability to walk,
      eat and even breathe. Since 1984, we have directed and invested in comprehensive
      research that has shaped the scientific community's understanding of SMA. On 23
      December, 2016, the Food and Drug Administration (FDA) announced approval of
      Spinraza, a treatment developed by Biogen and Ionis, making it the first-ever
      approved therapy for SMA. Cure SMA provided early research funding in 2003
      leading to the discovery of ISS-N1 sequence, now targeted by Spinraza. We are
      pleased that our strategy of providing seed funding for research to either
      identify new therapeutic strategies or de-risk early stage ones, has proven
      successful with Spinraza's approval. The approval of Spinraza provides great hope
      to the SMA community and represents decades of hard work and perseverance by
      families, researchers, pharmaceutical companies and the FDA. Our hope is that
      Spinraza is the leading edge of a robust drug pipeline, and with our deep
      expertise in every aspect of SMA, we remain committed to do everything we can to
      support research and drug development to achieve the greatest possible effect for
      each and every SMA patient.

PMID- 28504660
TI  - Physiological evolution: Genomic redox footprints.

PMID- 28504659
TI  - Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.
AB  - The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that
      spans the cell envelope and actively extrudes substrates, including macrolide
      antibiotics and polypeptide virulence factors. These transport processes are
      energized by the ATPase MacB, a member of the ATP-binding cassette (ABC)
      superfamily. We present an electron cryo-microscopy structure of the ABC-type
      tripartite assembly at near-atomic resolution. A hexamer of the periplasmic
      protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer
      in the inner membrane, generating a quaternary structure with a central channel
      for substrate translocation. A gating ring found in MacA is proposed to act as a
      one-way valve in substrate transport. The MacB structure features an atypical
      transmembrane domain with a closely packed dimer interface and a periplasmic
      opening that is the likely portal for substrate entry from the periplasm, with
      subsequent displacement through an allosteric transport mechanism.

PMID- 28504661
TI  - Circulating tumor cells as a biomarker for response to therapy in multiple
      myeloma patients treated within the GMMG-MM5 trial.

PMID- 28504662
TI  - Association between pretransplant iron overload determined by bone marrow
      pathological analysis and bacterial infection.

PMID- 28504663
TI  - A new time-dependent approach for assessment of the impact of invasive
      aspergillosis shows effect on short- but not on long-term survival of patients
      with AML or high-risk MDS.
AB  - Invasive aspergillosis (IA) has been reported to yield high mortality rates.
      Patients with an unfavourable prognostic haematological disease not only have a
      higher probability of developing IA but are also more likely to die due to causes
      directly related to the underlying disease. This complexity of risk mechanisms
      confounds the causal interpretation of IA occurrence and mortality. Full
      consideration of the changing patient characteristics over time is necessary to
      obtain reliable estimates of the correlation of IA with mortality. We studied the
      effect of IA on mortality in 167 consecutive patients starting with remission
      induction therapy for AML or of whom most patients continued to haematopoietic
      stem cell transplantation (HSCT). No standard antifungal prophylaxis was
      administered in the period before HSCT. Survival analyses were performed to
      determine risk estimates of IA for different phases of treatment before and after
      HSCT. Time-dependent adjustment for confounding variables was performed using Cox
      proportional hazards models. In 55 of 167 enroled patients, IA was diagnosed.
      Before HSCT, adjusted hazard ratios and 95% confidence intervals on mortality
      after the diagnosis of IA were 3.5 (1.7-7.5), 2.0 (0.69-5.9), 2.3 (0.79-6.8) and
      0.80 (0.49-1.4) within 30 days, between 30 and 60 days, between 60 and 90 days or
      more than 90 days, respectively. A similar pattern was observed after HSCT. The
      occurrence of IA did not significantly influence the decision to follow through
      with HSCT. The results provide new insights in short- and long-term survival of
      patients diagnosed with IA. A significantly increased mortality risk was only
      observed in the first month after diagnosis of IA. No unfavourable association
      with mortality was observed in the later course of treatment. The occurrence of
      IA did not affect the probability of attaining HSCT in our population.

PMID- 28504665
TI  - Upper GI GVHD: similar outcomes to other grade II graft-versus-host disease.
AB  - The significance of upper gastrointestinal tract (UGI) acute GVHD (aGVHD)
      compared with other grade II aGVHD is not clearly defined. We compared the
      outcomes of patients with grade II aGVHD with or without biopsy-proven UGI
      involvement in three groups: grade II aGVHD without UGI (n=178), grade II aGVHD
      with UGI and other sites (n=102) and isolated UGI aGVHD (n=32). The overall
      response (ORR) to steroids at day 28 differed among the three groups (76, 67 and
      91%, respectively, P=0.01), but was only marginally different in direct
      comparison with those without or with UGI aGVHD (P=0.07) or with isolated UGI
      aGVHD (P=0.06). In multivariate analysis, as compared with grade II aGVHD
      patients without UGI involvement, those with UGI involvement and those with
      isolated UGI aGVHD had similar risks of chronic GVHD, relapse and non-relapse
      mortality and similar disease-free survival and overall survival. Our data
      suggest that patients with UGI aGVHD have similar outcomes as those without UGI
      involvement, supporting the view that UGI aGVHD should still be included as a
      grade II-defining event.

PMID- 28504664
TI  - Pre-transplant ferritin, albumin and haemoglobin are predictive of survival
      outcome independent of disease risk index following allogeneic stem cell
      transplantation.
AB  - Prognostic biomarkers are useful in allogeneic stem cell transplantation (SCT) to
      predict survival and relapse outcomes. We sought to derive a prognostic scoring
      system, which augmented the predictive power of the disease risk index (DRI) by
      incorporating biomarkers and validating their significance after SCT. The
      outcomes of overall survival (OS) and relapse were assessed with non-relapse
      mortality (NRM) treated as a competing risk to relapse. Six hundred and two
      patients were identified through a retrospective analysis of allogeneic SCT
      recipients for haematological malignancy between 2000 and 2013 in a single
      centre. Multivariate analysis confirmed the significant predictors of OS pre-SCT
      were serum ferritin >1000 MUg/L (hazard ratio (HR) 1.94, 95% comorbidity index
      (CI): 1.44-2.60), Hb <100 g/L (HR 1.71, 95% CI: 1.27-2.30) and albumin <30 g/L
      (HR 2.65, 95% CI: 1.30-5.40). In combination with DRI, these biomarkers
      significantly improved the Harrell's C statistic (excluding biomarkers: C=0.60,
      95% CI: 0.57-0.64; with biomarkers: C=0.65, 95% CI: 0.62-0.69, P<0.001). Four
      prognostic groups were derived at the pre-SCT time point: Group 1 (Scores 0-1,
      n=180, HR=1 (ref)), Group 2 (Scores 2-5, n=298, HR 2.7, 95% CI: 1.8-3.9), Group 3
      (Scores 6-7, n=87, HR 4.5, 95% CI: 3.0-6.9) and Group 4 (scores 8-10, n=9, HR
      13.4, 95% CI: 5.9-30.2). These prognostic models were also predictive of relapse
      and NRM and remained valid at day 100, 12 months and 24 months post SCT.

PMID- 28504666
TI  - Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute
      myeloid leukemia.
AB  - AML is currently the first indication for allogeneic hematopoietic stem cell
      transplantation (allo-HSCT), as shown by international transplant registries. The
      conditioning regimens are classified as myeloablative conditioning, non
      myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such
      as anti-CD45 antibody have also been added to the conditioning regimen in an
      attempt to improve tumor cell kill. Refinement of standard regimens has led to a
      reduction of non-relapse mortality, also in the older age group over 60 or 70
      years of age. Relapse post allo-HSCT remains an important issue, especially for
      patients who undergo transplant with residual or refractory disease. In these
      patients, pre- and post-transplant interventions need to be considered.

PMID- 28504667
TI  - Rapid cloning of genes in hexaploid wheat using cultivar-specific long-range
      chromosome assembly.
AB  - Cereal crops such as wheat and maize have large repeat-rich genomes that make
      cloning of individual genes challenging. Moreover, gene order and gene sequences
      often differ substantially between cultivars of the same crop species. A major
      bottleneck for gene cloning in cereals is the generation of high-quality sequence
      information from a cultivar of interest. In order to accelerate gene cloning from
      any cropping line, we report 'targeted chromosome-based cloning via long-range
      assembly' (TACCA). TACCA combines lossless genome-complexity reduction via
      chromosome flow sorting with Chicago long-range linkage to assemble complex
      genomes. We applied TACCA to produce a high-quality (N50 of 9.76 Mb) de novo
      chromosome assembly of the wheat line CH Campala Lr22a in only 4 months. Using
      this assembly we cloned the broad-spectrum Lr22a leaf-rust resistance gene, using
      molecular marker information and ethyl methanesulfonate (EMS) mutants, and found
      that Lr22a encodes an intracellular immune receptor homologous to the Arabidopsis
      thaliana RPM1 protein.

PMID- 28504668
TI  - HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by
      NK cells.
AB  - Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the
      rejection of pluripotent stem cell (PSC)-derived products in allogeneic
      recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface
      expression of all class I molecules, but leaves the cells vulnerable to lysis by
      natural killer (NK) cells. Here we show that this 'missing-self' response can be
      prevented by forced expression of minimally polymorphic HLA-E molecules. We use
      adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the
      B2M locus in human PSCs in a manner that confers inducible, regulated, surface
      expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M
      and a peptide antigen), without surface expression of HLA-A, B or C. These HLA
      engineered PSCs and their differentiated derivatives are not recognized as
      allogeneic by CD8+ T cells, do not bind anti-HLA antibodies and are resistant to
      NK-mediated lysis. Our approach provides a potential source of universal donor
      cells for applications where the differentiated derivatives lack HLA class II
      expression.

PMID- 28504669
TI  - Nitric oxide prevents a pathogen-permissive granulocytic inflammation during
      tuberculosis.
AB  - Nitric oxide contributes to protection from tuberculosis. It is generally assumed
      that this protection is due to direct inhibition of Mycobacterium tuberculosis
      growth, which prevents subsequent pathological inflammation. In contrast, we
      report that nitric oxide primarily protects mice by repressing an interleukin-1-
      and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes
      bacterial replication. Using M. tuberculosis mutants as indicators of the
      pathogen's environment, we inferred that granulocytic inflammation generates a
      nutrient-replete niche that supports M. tuberculosis growth. Parallel clinical
      studies indicate that a similar inflammatory pathway promotes tuberculosis in
      patients. The human 12/15-lipoxygenase orthologue, ALOX12, is expressed in
      cavitary tuberculosis lesions; the abundance of its products correlates with the
      number of airway neutrophils and bacterial burden and a genetic polymorphism that
      increases ALOX12 expression is associated with tuberculosis risk. These data
      suggest that M. tuberculosis exploits neutrophilic inflammation to preferentially
      replicate at sites of tissue damage that promote contagion.

PMID- 28504670
TI  - Longevity of major coenzymes allows minimal de novo synthesis in microorganisms.
AB  - Coenzymes are vital for cellular metabolism and act on the full spectrum of
      enzymatic reactions. Intrinsic chemical reactivity, enzyme promiscuity and high
      flux through their catalytic cycles make coenzymes prone to damage. To counteract
      such compromising factors and ensure stable levels of functional coenzymes, cells
      use a complex interplay between de novo synthesis, salvage, repair and
      degradation. However, the relative contribution of these factors is currently
      unknown, as is the overall stability of coenzymes in the cell. Here, we use
      dynamic 13C-labelling experiments to determine the half-life of major coenzymes
      of Escherichia coli. We find that coenzymes such as pyridoxal 5-phosphate,
      flavins, nicotinamide adenine dinucleotide (phosphate) and coenzyme A are
      remarkably stable in vivo and allow biosynthesis close to the minimal necessary
      rate. In consequence, they are essentially produced to compensate for dilution by
      growth and passed on over generations of cells. Exceptions are antioxidants,
      which are short-lived, suggesting an inherent requirement for increased renewal.
      Although the growth-driven turnover of stable coenzymes is apparently subject to
      highly efficient end-product homeostasis, we exemplify that coenzyme pools are
      propagated in excess in relation to actual growth requirements. Additional
      testing of Bacillus subtilis and Saccharomyces cerevisiae suggests that coenzyme
      longevity is a conserved feature in biology.

PMID- 28504671
TI  - Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in
      spinal muscular atrophy.
AB  - Behavioral deficits in neurodegenerative diseases are often attributed to the
      selective dysfunction of vulnerable neurons via cell-autonomous mechanisms.
      Although vulnerable neurons are embedded in neuronal circuits, the contributions
      of their synaptic partners to disease process are largely unknown. Here we show
      that, in a mouse model of spinal muscular atrophy (SMA), a reduction in
      proprioceptive synaptic drive leads to motor neuron dysfunction and motor
      behavior impairments. In SMA mice or after the blockade of proprioceptive
      synaptic transmission, we observed a decrease in the motor neuron firing that
      could be explained by the reduction in the expression of the potassium channel
      Kv2.1 at the surface of motor neurons. Chronically increasing neuronal activity
      pharmacologically in vivo led to a normalization of Kv2.1 expression and an
      improvement in motor function. Our results demonstrate a key role of excitatory
      synaptic drive in shaping the function of motor neurons during development and
      the contribution of its disruption to a neurodegenerative disease.

PMID- 28504672
TI  - Identification of a motor-to-auditory pathway important for vocal learning.
AB  - Learning to vocalize depends on the ability to adaptively modify the temporal and
      spectral features of vocal elements. Neurons that convey motor-related signals to
      the auditory system are theorized to facilitate vocal learning, but the identity
      and function of such neurons remain unknown. Here we identify a previously
      unknown neuron type in the songbird brain that transmits vocal motor signals to
      the auditory cortex. Genetically ablating these neurons in juveniles disrupted
      their ability to imitate features of an adult tutor's song. Ablating these
      neurons in adults had little effect on previously learned songs but interfered
      with their ability to adaptively modify the duration of vocal elements and
      largely prevented the degradation of songs' temporal features that is normally
      caused by deafening. These findings identify a motor to auditory circuit
      essential to vocal imitation and to the adaptive modification of vocal timing.

PMID- 28504673
TI  - A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during
      in vivo brain imaging.
AB  - Pericytes and smooth muscle cells are integral components of the brain
      microvasculature. However, no techniques exist to unambiguously identify these
      cell types, greatly limiting their investigation in vivo. Here we show that the
      fluorescent Nissl dye NeuroTrace 500/525 labels brain pericytes with specificity,
      allowing high-resolution optical imaging in the live mouse. We demonstrate that
      capillary pericytes are a population of mural cells with distinct morphological,
      molecular and functional features that do not overlap with precapillary or
      arteriolar smooth muscle actin-expressing cells. The remarkable specificity for
      dye uptake suggests that pericytes have molecular transport mechanisms not
      present in other brain cells. We demonstrate feasibility of longitudinal pericyte
      imaging during microvascular development and aging and in models of brain
      ischemia and Alzheimer's disease. The ability to easily label pericytes in any
      mouse model opens the possibility of a broad range of investigations of mural
      cells in vascular development, neurovascular coupling and neuropathology.

PMID- 28504674
TI  - Printable elastic conductors by in situ formation of silver nanoparticles from
      silver flakes.
AB  - Printable elastic conductors promise large-area stretchable sensor/actuator
      networks for healthcare, wearables and robotics. Elastomers with metal
      nanoparticles are one of the best approaches to achieve high performance, but
      large-area utilization is limited by difficulties in their processability. Here
      we report a printable elastic conductor containing Ag nanoparticles that are
      formed in situ, solely by mixing micrometre-sized Ag flakes, fluorine rubbers,
      and surfactant. Our printable elastic composites exhibit conductivity higher than
      4,000 S cm-1 (highest value: 6,168 S cm-1) at 0% strain, and 935 S cm-1 when
      stretched up to 400%. Ag nanoparticle formation is influenced by the surfactant,
      heating processes, and elastomer molecular weight, resulting in a drastic
      improvement of conductivity. Fully printed sensor networks for stretchable robots
      are demonstrated, sensing pressure and temperature accurately, even when
      stretched over 250%.

PMID- 28504675
TI  - Giant thermal Hall effect in multiferroics.
AB  - Multiferroics, in which dielectric and magnetic orders coexist and couple with
      each other, attract renewed interest for their cross-correlated phenomena,
      offering a fundamental platform for novel functionalities. Elementary excitations
      in such systems are strongly affected by the lattice-spin interaction, as
      exemplified by the electromagnons and the magneto-thermal transport. Here we
      report an unprecedented coupling between magnetism and phonons in multiferroics,
      namely, the giant thermal Hall effect. The thermal transport of insulating polar
      magnets (ZnxFe1-x)2Mo3O8 is dominated by phonons, yet extremely sensitive to the
      magnetic structure. In particular, large thermal Hall conductivities are observed
      in the ferrimagnetic phase, indicating unconventional lattice-spin interactions
      and a new mechanism for the Hall effect in insulators. Our results show that the
      thermal Hall effect in multiferroic materials can be an effective probe for
      strong lattice-spin interactions and provide a new tool for magnetic control of
      thermal currents.

PMID- 28504676
TI  - Developing Spindlin1 small-molecule inhibitors by using protein microarrays.
AB  - The discovery of inhibitors of methyl- and acetyl-binding domains has provided
      evidence for the 'druggability' of epigenetic effector molecules. The small
      molecule probe UNC1215 prevents methyl-dependent protein-protein interactions by
      engaging the aromatic cage of MBT domains and, with lower affinity, Tudor
      domains. Using a library of tagged UNC1215 analogs, we screened a protein-domain
      microarray of human methyllysine effector molecules to rapidly detect compounds
      with new binding profiles with either increased or decreased specificity. Using
      this approach, we identified a compound (EML405) that acquired a novel
      interaction with the Tudor-domain-containing protein Spindlin1 (SPIN1).
      Structural studies facilitated the rational synthesis of SPIN1 inhibitors with
      increased selectivity (EML631-633), which engage SPIN1 in cells, block its
      ability to 'read' H3K4me3 marks and inhibit its transcriptional-coactivator
      activity. Protein microarrays can thus be used as a platform to 'target-hop' and
      identify small molecules that bind and compete with domain-motif interactions.

PMID- 28504677
TI  - beta-Lactone formation during product release from a nonribosomal peptide
      synthetase.
AB  - Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic
      assembly lines that polymerize amino acids into a myriad of biologically active
      nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse
      release strategies for off-loading thioester-tethered polymeric peptides from
      termination modules typically via hydrolysis, aminolysis, or cyclization to
      provide mature antibiotics as carboxylic acids/esters, amides, and
      lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of
      a highly strained beta-lactone ring during TE-mediated cyclization of a beta
      hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly
      line. The Obi NRPS (ObiF) contains a type I TE domain with a rare catalytic
      cysteine residue that plays a direct role in beta-lactone ring formation. We
      present a detailed genetic and biochemical characterization of the entire Obi
      biosynthetic gene cluster in plant-associated Pseudomonas fluorescens ATCC 39502
      that establishes a general strategy for beta-lactone biogenesis.

PMID- 28504678
TI  - A conserved threonine prevents self-intoxication of enoyl-thioester reductases.
AB  - Enzymes are highly specific biocatalysts, yet they can promote unwanted side
      reactions. Here we investigated the factors that direct catalysis in the enoyl
      thioester reductase Etr1p. We show that a single conserved threonine is essential
      to suppress the formation of a side product that would otherwise act as a high
      affinity inhibitor of the enzyme. Substitution of this threonine with isosteric
      valine increases side-product formation by more than six orders of magnitude,
      while decreasing turnover frequency by only one order of magnitude. Our results
      show that the promotion of wanted reactions and the suppression of unwanted side
      reactions operate independently at the active site of Etr1p, and that the active
      suppression of side reactions is highly conserved in the family of medium-chain
      dehydrogenases/reductases (MDRs). Our discovery emphasizes the fact that the
      active destabilization of competing transition states is an important factor
      during catalysis that has implications for the understanding and the de novo
      design of enzymes.

PMID- 28504680
TI  - Nm-seq maps 2'-O-methylation sites in human mRNA with base precision.
AB  - The ribose of RNA nucleotides can be 2'-O-methylated (Nm). Despite advances in
      high-throughput detection, the inert chemical nature of Nm still limits
      sensitivity and precludes mapping in mRNA. We leveraged the differential
      reactivity of 2'-O-methylated and 2'-hydroxylated nucleosides to periodate
      oxidation to develop Nm-seq, a sensitive method for transcriptome-wide mapping of
      Nm with base precision. Nm-seq uncovered thousands of Nm sites in human mRNA with
      features suggesting functional roles.

PMID- 28504681
TI  - Fused cerebral organoids model interactions between brain regions.
AB  - Human brain development involves complex interactions between different regions,
      including long-distance neuronal migration or formation of major axonal tracts.
      Different brain regions can be cultured in vitro within 3D cerebral organoids,
      but the random arrangement of regional identities limits the reliable analysis of
      complex phenotypes. Here, we describe a coculture method combining brain regions
      of choice within one organoid tissue. By fusing organoids of dorsal and ventral
      forebrain identities, we generate a dorsal-ventral axis. Using fluorescent
      reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from
      ventral to dorsal forebrain and describe methodology for time-lapse imaging of
      human interneuron migration. Our results demonstrate that cerebral organoid
      fusion cultures can model complex interactions between different brain regions.
      Combined with reprogramming technology, fusions should offer researchers the
      possibility to analyze complex neurodevelopmental defects using cells from
      neurological disease patients and to test potential therapeutic compounds.

PMID- 28504679
TI  - Generation of pure GABAergic neurons by transcription factor programming.
AB  - Approaches to differentiating pluripotent stem cells (PSCs) into neurons
      currently face two major challenges-(i) generated cells are immature, with
      limited functional properties; and (ii) cultures exhibit heterogeneous neuronal
      subtypes and maturation stages. Using lineage-determining transcription factors,
      we previously developed a single-step method to generate glutamatergic neurons
      from human PSCs. Here, we show that transient expression of the transcription
      factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic
      neurons from human PSCs with a high degree of synaptic maturation. These AD
      induced neuronal (iN) cells represent largely nonoverlapping populations of
      GABAergic neurons that express various subtype-specific markers. We further used
      AD-iN cells to establish that human collybistin, the loss of gene function of
      which causes severe encephalopathy, is required for inhibitory synaptic function.
      The generation of defined populations of functionally mature human GABAergic
      neurons represents an important step toward enabling the study of diseases
      affecting inhibitory synaptic transmission.

PMID- 28504682
TI  - Testing for differential abundance in mass cytometry data.
AB  - When comparing biological conditions using mass cytometry data, a key challenge
      is to identify cellular populations that change in abundance. Here, we present a
      computational strategy for detecting 'differentially abundant' populations by
      assigning cells to hyperspheres, testing for significant differences between
      conditions and controlling the spatial false discovery rate. Our method
      (http://bioconductor.org/packages/cydar) outperforms other approaches in
      simulations and finds novel patterns of differential abundance in real data.

PMID- 28504683
TI  - Normalizing single-cell RNA sequencing data: challenges and opportunities.
AB  - Single-cell transcriptomics is becoming an important component of the molecular
      biologist's toolkit. A critical step when analyzing data generated using this
      technology is normalization. However, normalization is typically performed using
      methods developed for bulk RNA sequencing or even microarray data, and the
      suitability of these methods for single-cell transcriptomics has not been
      assessed. We here discuss commonly used normalization approaches and illustrate
      how these can produce misleading results. Finally, we present alternative
      approaches and provide recommendations for single-cell RNA sequencing users.

PMID- 28504684
TI  - Fully automated 5-plex fluorescent immunohistochemistry with tyramide signal
      amplification and same species antibodies.
AB  - The ability to simultaneously visualize the presence, abundance, location and
      functional state of many targets in cells and tissues has been described as a
      true next-generation approach in immunohistochemistry (IHC). A typical
      requirement for multiplex IHC (mIHC) is the use of different animal species for
      each primary (1 degrees Ab) and secondary (2 degrees Ab) antibody pair. Although
      1 degrees Abs from different species have been used with differently labeled
      species-specific 2 degrees Abs, quite often the appropriate combination of
      antibodies is not available. More recently, sequential detection of multiple
      antigens using 1 degrees Abs from the same species used a microwaving treatment
      between successive antigen detection cycles to elute previously bound 1 degrees
      Ab/2 degrees Ab complex and therefore to prevent the cross-reactivity of anti
      species 2 degrees Abs used in subsequent detection cycles. We present here a
      fully automated 1 degrees Ab/2 degrees Ab complex heat deactivation (HD) method
      on Ventana's BenchMark ULTRA slide stainer. This method is applied to detection
      using fluorophore-conjugated tyramide deposited on the tissue and takes advantage
      of the strong covalent bonding of the detection substrate to the tissue,
      preventing its elution in the HD process. The HD process was characterized for
      (1) effectiveness in preventing Ab cross-reactivity, (2) impact on the epitopes
      and (3) impact on the fluorophores. An automated 5-plex fluorescent IHC assay was
      further developed using the HD method and rabbit 1 degrees Abs for CD3, CD8,
      CD20, CD68 and FoxP3 immune biomarkers in human tissue specimens. The
      fluorophores were carefully chosen and the narrow-band filters were designed to
      allow visualization of the staining under fluorescent microscope with minimal
      bleed through. The automated 5-plex fluorescent IHC assay achieved staining
      results comparable to the respective single-plex chromogenic IHC assays. This
      technology enables automated mIHC using unmodified 1 degrees Abs from same
      species and the corresponding anti-species 2 degrees Ab on a clinically
      established automated platform to ensure staining quality, reliability and
      reproducibility.

PMID- 28504685
TI  - Spleen-derived lipocalin-2 in the portal vein regulates Kupffer cells activation
      and attenuates the development of liver fibrosis in mice.
AB  - The liver has an immune tolerance against gut-derived products from the portal
      vein (PV). A disruption of the gut-liver axis leads to liver injury and fibrosis.
      The spleen is connected to the PV and regulates immune functions. However,
      possible splenic effects on liver fibrosis development are unclear. Lipocalin-2
      (Lcn2) is an antimicrobial protein that regulates macrophage activation. To
      clarify the role of the spleen in liver fibrosis development, we induced liver
      fibrosis in mice after splenectomy, and investigated liver fibrosis development.
      Liver fibrosis resulted in significantly increased splenic Lcn2 levels, but all
      other measured cytokine levels were unchanged. Splenectomized mice showed
      enhanced liver fibrosis and inflammation accompanied by significantly decreased
      Lcn2 levels in PV. Lipopolysaccharide-stimulated primary Kupffer cells, resident
      liver macrophages, which were treated with recombinant Lcn2 (rLcn2) produced less
      tumor necrosis factor-alpha and Ccl2 and the activation of hepatic stellate
      cells, the effector cells for collagen production in the liver, was suppressed by
      co-culture with rLcn2-treated Kupffer cells. In addition, the involvement of gut
      derived products in splenectomized mice was evaluated by gut sterilization.
      Interestingly, gut sterilization blocked the effect of splenectomy on liver
      fibrosis development. In conclusion, spleen deficiency accelerated liver fibrosis
      development and decreased PV Lcn2 levels. The mechanism of splenic protection
      against liver fibrosis development may involve the splenic Lcn2, triggered by gut
      derived products that enter the liver through the PV, regulates Kupffer cells
      activated by the gut-liver axis. Thus, the splenic Lcn2 may have an important
      role in regulating the immune tolerance of the liver in liver fibrosis
      development.

PMID- 28504686
TI  - NDGA-P21, a novel derivative of nordihydroguaiaretic acid, inhibits glioma cell
      proliferation and stemness.
AB  - Nordihydroguaiaretic acid (NDGA) and its synthetic chiral analog dl
      nordihydroguaiaretic acid (Nordy) show collective benefits in anti-tumor, and
      defending against viral and bacterial infections. Here, we synthetized a new
      derivative-NDGA-P21 based on NDGA structure. Regardless of the structural
      similarity, NDGA-P21 exhibited stronger capability in suppression of glioblastoma
      (GBM) cell growth as compared to Nordy. Mechanically, NDGA-P21 is able to arrest
      cell cycle of GBM cells in G0/G1 phase, and to block cell proliferation
      sequentially. It is important to note that NDGA-P21 is able to impair the
      stemness of glioma stem-like cells (GSLCs) via measurement of colony formation
      and sphere formation. Taken together, the novel NDGA-based compound NDGA-P21
      exhibits potential therty -20 apeutic implications through inhibiting
      proliferation of glioma cells and self-renewal capability of GSLCs.

PMID- 28504687
TI  - The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14
      suppressed tumor proliferation and induced apoptosis.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At
      present, there is no well-established targeted drug for majority of patients. The
      kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and
      is dysregulated in multiple cancers. The objectives of this study were to
      evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate
      its biological functions in MB pathogenesis. By quantitative RT-PCR and
      immunohistochemistry, we found KIF14 was overexpressed in MB. Increased KIF14
      expression at protein level was strongly associated with shorter progression-free
      survival (P=0.0063) and overall survival (P=0.0083). Fluorescence in situ
      hybridization (FISH) analysis confirmed genomic gain of chromosome 1q in 17/93
      (18.3%) of MB. Combined genetic and immunohistochemical analyses revealed that
      76.5% of MB with 1q gain showed consistent overexpression of KIF14, and a tight
      link between chromosome 1q gain and KIF14 overexpression (P=0.03). Transient,
      siRNAs-mediated downregulation of KIF14 suppressed cell proliferation and induced
      apoptosis in two MB cell lines. Stably KIF14 knockdown by shRNAs inhibited cell
      viability, colony formation, migration and invasion, and tumor sphere formation
      in MB cells. We conclude that KIF14 is dysregulated in MB and is an adverse
      prognostic factor for survival. Furthermore, KIF14 is part of MB biology and is a
      potential therapeutic target for MB.

PMID- 28504689
TI  - Molecular signaling in multiple myeloma: association of RAS/RAF mutations and
      MEK/ERK pathway activation.
AB  - Multiple myeloma (MM) is a plasma cell malignancy that is still considered to be
      incurable in most cases. A dominant mutation cluster has been identified in
      RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK
      signaling as a therapeutic target. As yet, however, the clinical relevance of
      this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM
      have been mixed. We therefore assessed RAS/RAF mutation status and MEK/ERK
      pathway activation by both targeted sequencing and phospho-ERK
      immunohistochemistry in 180 tissue biopsies from 103 patients with newly
      diagnosed MM (NDMM) and 77 patients with relapsed/refractory MM (rrMM). We found
      a significant enrichment of RAS/BRAF mutations in rrMM compared to NDMM
      (P=0.011), which was mainly due to an increase of NRAS mutations (P=0.010). As
      expected, BRAF mutations were significantly associated with activated downstream
      signaling. However, only KRAS and not NRAS mutations were associated with pathway
      activation compared to RAS/BRAFwt (P=0.030). More specifically, only KRASG12D and
      BRAFV600E were consistently associated with ERK activation (P<0.001 and P=0.006,
      respectively). Taken together, these results suggest the need for a more specific
      stratification strategy consisting of both confirmation of protein-level pathway
      activation as well as detailed RAS/RAF mutation status to allow for a more
      precise and more effective application of targeted therapies, for example, with
      BRAF/MEK inhibitors in MM.

PMID- 28504688
TI  - Accelerated atherosclerosis development in C57Bl6 mice by overexpressing AAV
      mediated PCSK9 and partial carotid ligation.
AB  - Studying the role of a particular gene in atherosclerosis typically requires a
      time-consuming and often difficult process of generating double knockouts or
      transgenics on ApoE-/- or LDL receptor (LDLR)-/- background. Recently, it was
      reported that adeno-associated-virus-8 (AAV8)-mediated overexpression of PCSK9
      (AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6
      wild-type (C57) mice, it took ~3 months to develop atherosclerosis. Our partial
      carotid ligation model is used to rapidly develop atherosclerosis by inducing
      disturbed flow in the left common carotid artery within 2 weeks in ApoE-/- or
      LDLR-/- mice. Here, we combined these two approaches to develop an accelerated
      model of atherosclerosis in C57 mice. C57 mice were injected with AAV9-PCSK9 or
      AAV9-luciferase (control) and high-fat diet was initiated. A week later, partial
      ligation was performed. Compared to the control, AAV-PCSK9 led to elevated serum
      PCSK9, hypercholesterolemia, and rapid atherosclerosis development within 3 weeks
      as determined by gross plaque imaging, and staining with Oil-Red-O, Movat's
      pentachrome, and CD45 antibody. These plaque lesions were comparable to the
      atherosclerotic lesions that have been previously observed in ApoE-/- or LDLR-/-
      mice that were subjected to partial carotid ligation and high-fat diet. Next, we
      tested whether our method can be utilized to rapidly determine the role of a
      particular gene in atherosclerosis. Using eNOS-/- and NOX1-/y mice on C57
      background, we found that the eNOS-/- mice developed more advanced lesions, while
      the NOX1-/y mice developed less atherosclerotic lesions as compared to the C57
      controls. These results are consistent with the previous findings using double
      knockouts (eNOS-/-_ApoE-/- and NOX1-/y_ApoE-/-). AAV9-PCSK9 injection followed by
      partial carotid ligation is an effective and time-saving approach to rapidly
      induce atherosclerosis. This accelerated model is well-suited to quickly
      determine the role of gene(s) interest without generating double or triple
      knockouts.

PMID- 28504690
TI  - MicroRNA-645 is an oncogenic regulator in colon cancer.
AB  - Despite advances in early diagnosis and the development of molecularly targeted
      therapy, curative treatment of colon cancer once it has metastasized is yet to be
      accomplished. This is closely associated with deregulated CRC cell proliferation
      and resistance to apoptosis. Here we reveal that upregulation of microRNA-645
      (miR-645) through DNA copy number gain is responsible for enhanced proliferation
      and resistance to apoptosis in colon cancer. MiR-645 was upregulated in most
      colon cancer tissues related to adjacent normal mucosa. This appeared to be
      associated with amplification of a section of chromosome 20q13.13, where miR-645
      is located. Inhibition of miR-645 reduced proliferation and enhanced sensitivity
      to apoptosis triggered by the chemotherapeutic drugs 5-fluorouracil and cisplatin
      in CRC cells, and retarded colon cancer xenograft growth. Conversely,
      overexpression of miR-645 in normal colon epithelial cells enhanced proliferation
      and triggered anchorage-independent cell growth. Although SRY-related HMG-box 30
      (SOX30) was identified as a miR-645 target, its expression was only partially
      affected by miR-645, suggesting that miR-645 is a fine-tuning mechanism of SOX30
      expression. Moreover, overexpression of SOX30 only moderately inhibited promotion
      of CRC cell proliferation by miR-645, indicating that miR-645 may have more
      targets that contribute to its pro-proliferation effect in colon cancer.
      Together, this study reveals that miR-645 can regulate oncogenesis in colon
      cancer with SOX30 being one of its targets.

PMID- 28504691
TI  - CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in
      ovarian cancer patients.
AB  - Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian
      cancer (EOC), but the underlying mechanisms have not been fully elucidated. The
      CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites,
      but its role in ovarian cancer metastasis is largely unknown. Herein, we first
      screened two independent cohorts of high-grade serous ovarian cancers (HGSCs,
      discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3
      expression. In primary tumors, CXCR3 was particularly overexpressed by tumor
      cells at the invasive front. In intraabdominal metastases, tumor cells revealed a
      strong CXCR3 expression regardless of its expression in the corresponding primary
      tumor, suggesting a selection of CXCR3-overexpressing cancer cells into
      peritoneal niches. In support of this, CXCR3 mediated the migration of tumor cell
      lines OVCAR3 and SKOV3 toward malignant ascites, which was inhibited by a
      monoclonal anti-CXCR3 antibody in vitro. These results were prospectively
      validated in ascites-derived tumor cells from EOC patients ex vivo (n=9).
      Moreover, tumor cell-associated overexpression of CXCR3 in advanced ovarian
      cancer patients was associated with a reduced progression-free survival (PFS) and
      overall survival (OS), which remained independent of optimal debulking, age, FIGO
      stage and lymph node involvement (PFS: hazard ratio (HR) 2.11, 95% confidence
      interval (CI) 1.30-3.45, P=0.003; OS: HR 2.36, 95% CI 1.50-3.71, P<0.001). These
      results in ovarian cancer patients identify CXCR3 as a potential new target to
      confine peritoneal spread in ovarian cancer after primary cytoreductive surgery.

PMID- 28504692
TI  - Mint3-mediated L1CAM expression in fibroblasts promotes cancer cell proliferation
      via integrin alpha5beta1 and tumour growth.
AB  - Fibroblasts are some of the major cells in tumour tissues that influence tumour
      progression and drug resistance. However, our understanding on fibroblast
      mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3
      (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even
      during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3
      promotes ATP production via glycolysis by activating HIF-1 in cancer cells and
      macrophages, the biological role of Mint3-mediated HIF-1 activation in
      fibroblasts remains unclear. To address this, we examined whether Mint3 in
      fibroblasts contributes to tumour growth. Mint3 depletion in mouse embryonic
      fibroblasts (MEFs) decreased tumour growth of co-injected human breast cancer
      cells, MDA-MB-231 and epidermoid carcinoma A431 cells in mice. In MEFs, Mint3
      also promoted cancer cell proliferation in vitro in a cell-cell contact-dependent
      manner. Mint3-mediated cancer cell proliferation depended on HIF-1, and further
      gene expression analysis revealed that the cell adhesion molecule, L1 cell
      adhesion molecule (L1CAM), was induced by Mint3 and HIF-1 in fibroblasts. Mint3
      mediated L1CAM expression in fibroblasts stimulated the ERK signalling pathway
      via integrin alpha5beta1 in cancer cells, and promoted cancer cell proliferation
      in vitro and tumour growth. In cancer-associated fibroblasts (CAFs), knockdown of
      MT1-MMP, which promotes Mint3-mediated HIF-1 activation, or Mint3 decreased L1CAM
      expression. As MEFs, CAFs also promoted cancer cell proliferation in vitro, and
      tumour growth via Mint3 and L1CAM. In human breast cancer specimens, the number
      of fibroblasts expressing L1CAM, Mint3 and MT1-MMP was higher in cancer regions
      than in adjacent benign regions. In addition, more phospho-ERK1/2-positive cancer
      cells existed in the peripheral region surrounded by the stroma than in the
      central region of solid breast cancer nest. Thus, Mint3 in fibroblasts might be a
      good target for cancer therapy by regulating cancer cell-stromal cell
      communication.

PMID- 28504693
TI  - Cyclin-dependent kinase 7 is a therapeutic target in high-grade glioma.
AB  - High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells
      within HGG tumors are highly heterogeneous. This renders the tumors unresponsive
      or able to adapt to therapeutics targeted at single pathways, thereby causing
      treatment failure. To overcome this, we focused on cyclin-dependent kinase 7
      (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG
      pathogenesis: cell cycle progression and RNA polymerase-II-based transcription.
      We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient
      derived primary HGG cell lines and ex vivo HGG patient tissue slices, using
      proliferation assays, microarray analysis, high-resolution respirometry, cell
      cycle analysis and in vivo tumor orthografts. The cellular processes affected by
      CDK7 inhibition were analyzed by reverse transcriptase-quantitative PCR, western
      blot, flow cytometry and immunofluorescence. THZ1 perturbed the transcriptome and
      disabled CDK activation, leading to cell cycle arrest at G2 and DNA damage. THZ1
      halted transcription of the nuclear-encoded mitochondrial ribosomal genes,
      reducing mitochondrial translation and oxidative respiration. It also inhibited
      the expression of receptor tyrosine kinases such as epidermal growth factor
      receptor (EGFR) and platelet-derived growth factor receptor-alpha (PDGFR-alpha),
      reducing signaling flux through the AKT, extracellular-signal-regulated kinase
      1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3)
      downstream pathways. Finally, THZ1 disrupted nucleolar, Cajal body and nuclear
      speckle formation, resulting in reduced cytosolic translation and malfunction of
      the spliceosome and thus leading to aberrant mRNA processing. These findings
      indicate that CDK7 is crucial for gliomagenesis, validate CDK7 as a therapeutic
      target and provide new insight into the cellular processes that are affected by
      THZ1 and induce antitumor activity.

PMID- 28504694
TI  - The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen
      signalling in prostate cancer cells.
AB  - Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities
      across several cellular compartments including mitochondria, cell membrane and
      the nucleus. PHB and the steroid-activated androgen receptor (AR) have an
      interplay where AR downregulates PHB, and PHB represses AR. Additionally, their
      cellular locations and chromatin interactions are in dynamic opposition. We
      investigated the mechanisms of cell cycle inhibition by PHB and how this is
      modulated by AR in prostate cancer. Using a prostate cancer cell line
      overexpressing PHB, we analysed the gene expression changes associated with PHB
      mediated cell cycle arrest. Over 1000 gene expression changes were found to be
      significant and gene ontology analysis confirmed PHB-mediated repression of genes
      essential for DNA replication and synthesis, for example, MCMs and TK1, via an
      E2F1 regulated pathway-agreeing with its G1/S cell cycle arrest activity. PHB is
      known to inhibit E2F1-mediated transcription, and the PHB:E2F1 interaction was
      seen in LNCaP nuclear extracts, which was then reduced by androgen treatment.
      Upon two-dimensional western blot analysis, the PHB protein itself showed
      androgen-mediated charge differentiation (only in AR-positive cells), indicating
      a potential dephosphorylation event. Kinexus phosphoprotein array analysis
      indicated that Src kinase was the main interacting intracellular signalling hub
      in androgen-treated LNCaP cells, and that Src inhibition could reduce this AR
      mediated charge differentiation. PHB charge change may be associated with rapid
      dissociation from chromatin and E2F1, allowing the cell cycle to proceed. The AR
      and androgens may deactivate the repressive functions of PHB upon E2F1 leading to
      cell cycle progression, and indicates a role for AR in DNA replication licensing.

PMID- 28504695
TI  - Epigenetic pathway inhibitors represent potential drugs for treating pancreatic
      and bronchial neuroendocrine tumors.
AB  - Cancer is associated with alterations in epigenetic mechanisms such as histone
      modifications and methylation of DNA, and inhibitors targeting epigenetic
      mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors
      (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year
      survivals of <50% and as low as 5%, respectively, represent targets for such
      drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple
      endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies
      histones by interacting with histone methyltransferases. We assessed 9 inhibitors
      of epigenetic pathways, for their effects on proliferation, by CellTiter Blue
      assay, and apoptosis, by CaspaseGlo assay, using 1 PNET and 2 BNET cell lines.
      Two inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, targeting the bromo and
      extra terminal (BET) protein family which bind acetylated histone residues, were
      most effective in decreasing proliferation (by 40-85%, P<0.001) and increasing
      apoptosis (by 2-3.6 fold, P<0.001) in all 3 NET cell lines. The anti
      proliferative effects of JQ1 and PFI-1 remained present for at least 48 hours
      after removal of the compound. JQ1, but not PFI-1, had cell cycle effects,
      assessed by propidium iodide staining and flow cytometry, resulting in increased
      and decreased proportions of NET cells in G1, and S and G2 phases, respectively.
      RNA Sequencing analysis revealed that these JQ1 effects were associated with
      increased histone 2B expression, and likely mediated through altered activity of
      bromodomain-containing (Brd) proteins. Assessment of JQ1 in vivo, using a
      pancreatic beta cell-specific conditional Men1 knockout mouse model that develops
      PNETs, revealed that JQ1 significantly reduced proliferation (by ~50%, P<0.0005),
      assessed by bromodeoxyuridine incorporation, and increased apoptosis (by ~3 fold,
      P<0.0005), assessed by terminal deoxynucleotidyl transferase dUTP nick end
      labelling, of PNETs. Thus, our studies demonstrate that BET protein inhibitors
      may provide new treatments for NETs.

PMID- 28504696
TI  - 5-Formylcytosine does not change the global structure of DNA.
AB  - The mechanism by which the recently identified DNA modification 5-formylcytosine
      (fC) is recognized by epigenetic writer and reader proteins is not known.
      Recently, an unusual DNA structure, F-DNA, has been proposed as the basis for
      enzyme recognition of clusters of fC. We used NMR and X-ray crystallography to
      compare several modified DNA duplexes with unmodified analogs and found that in
      the crystal state the duplexes all belong to the A family, whereas in solution
      they are all members of the B family. We found that, contrary to previous
      findings, fC does not significantly affect the structure of DNA, although there
      are modest local differences at the modification sites. Hence, global
      conformation changes are unlikely to account for the recognition of this modified
      base, and our structural data favor a mechanism that operates at base-pair
      resolution for the recognition of fC by epigenome-modifying enzymes.

PMID- 28504699
TI  - Expansion of the redox-sensitive proteome coincides with the plastid
      endosymbiosis.
AB  - The redox-sensitive proteome (RSP) consists of protein thiols that undergo redox
      reactions, playing an important role in coordinating cellular processes. Here, we
      applied a large-scale phylogenomic reconstruction approach in the model diatom
      Phaeodactylum tricornutum to map the evolutionary origins of the eukaryotic RSP.
      The majority of P. tricornutum redox-sensitive cysteines (76%) is specific to
      eukaryotes, yet these are encoded in genes that are mostly of a prokaryotic
      origin (57%). Furthermore, we find a threefold enrichment in redox-sensitive
      cysteines in genes that were gained by endosymbiotic gene transfer during the
      primary plastid acquisition. The secondary endosymbiosis event coincides with
      frequent introduction of reactive cysteines into existing proteins. While the
      plastid acquisition imposed an increase in the production of reactive oxygen
      species, our results suggest that it was accompanied by significant expansion of
      the RSP, providing redox regulatory networks the ability to cope with fluctuating
      environmental conditions.

PMID- 28504697
TI  - The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17
      cells and Treg cells.
AB  - An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells)
      and the inflammatory TH17 subset of helper T cells leads to the development of
      autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of
      TEAD transcription factors of Hippo signaling, was expressed under TH17 cell
      inducing conditions and was required for TH17 differentiation and TH17 cell
      mediated inflammatory diseases. TAZ was a critical co-activator of the TH17
      defining transcription factor RORgammat. In addition, TAZ attenuated Treg cell
      development by decreasing acetylation of the Treg cell master regulator Foxp3
      mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for
      proteasomal degradation. In contrast, under Treg cell-skewing conditions, TEAD1
      expression and sequestration of TAZ from the transcription factors RORgammat and
      Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or
      overexpression of TEAD1 induced Treg cell differentiation, whereas expression of
      a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation.
      Our results demonstrate a pivotal role for TAZ in regulating the differentiation
      of Treg cells and TH17 cells.

PMID- 28504698
TI  - Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the
      endothelial receptor LYVE-1.
AB  - Trafficking of tissue dendritic cells (DCs) via lymph is critical for the
      generation of cellular immune responses in draining lymph nodes (LNs). In the
      current study we found that DCs docked to the basolateral surface of lymphatic
      vessels and transited to the lumen through hyaluronan-mediated interactions with
      the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup
      like structures. Furthermore, we show that targeted deletion of the gene Lyve1,
      antibody blockade or depletion of the DC hyaluronan coat not only delayed
      lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8+
      T cell responses in skin-draining LNs. Our findings uncovered a previously
      unknown function for LYVE-1 and show that transit through the lymphatic network
      is initiated by the recognition of leukocyte-derived hyaluronan.

PMID- 28504700
TI  - Lineage-specific functions of TET1 in the postimplantation mouse embryo.
AB  - The mammalian TET enzymes catalyze DNA demethylation. While they have been
      intensely studied as major epigenetic regulators, little is known about their
      physiological roles and the extent of functional redundancy following embryo
      implantation. Here we define non-redundant roles for TET1 at an early
      postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are
      not detectably expressed. TET1 regulates numerous genes defining differentiation
      programs in the epiblast and extraembryonic ectoderm. In epiblast cells, TET1
      demethylates gene promoters via hydroxymethylation and maintains telomere
      stability. Surprisingly, TET1 represses a majority of epiblast target genes
      independently of methylation changes, in part through regulation of the gene
      encoding the transcriptional repressor JMJD8. Dysregulated gene expression in the
      absence of TET1 causes embryonic defects, which are partially penetrant in an
      inbred strain but fully lethal in non-inbred mice. Collectively, our study
      highlights an interplay between the catalytic and non-catalytic activities of
      TET1 that is essential for normal development.

PMID- 28504701
TI  - Paused RNA polymerase II inhibits new transcriptional initiation.
AB  - RNA polymerase II (Pol II) pauses downstream of the transcription initiation site
      before beginning productive elongation. This pause is a key component of metazoan
      gene expression regulation. Some promoters have a strong disposition for Pol II
      pausing and often mediate faster, more synchronous changes in expression. This
      requires multiple rounds of transcription and thus cannot rely solely on pause
      release. However, it is unclear how pausing affects the initiation of new
      transcripts during consecutive rounds of transcription. Using our recently
      developed ChIP-nexus method, we find that Pol II pausing inhibits new initiation.
      We propose that paused Pol II helps prevent new initiation between transcription
      bursts, which may reduce noise.

PMID- 28504704
TI  - Glyphosate resistance: Of superweeds and survivors.

PMID- 28504702
TI  - PGBD5 promotes site-specific oncogenic mutations in human tumors.
AB  - Genomic rearrangements are a hallmark of human cancers. Here, we identify the
      piggyBac transposable element derived 5 (PGBD5) gene as encoding an active DNA
      transposase expressed in the majority of childhood solid tumors, including lethal
      rhabdoid tumors. Using assembly-based whole-genome DNA sequencing, we found
      previously undefined genomic rearrangements in human rhabdoid tumors. These
      rearrangements involved PGBD5-specific signal (PSS) sequences at their
      breakpoints and recurrently inactivated tumor-suppressor genes. PGBD5 was
      physically associated with genomic PSS sequences that were also sufficient to
      mediate PGBD5-induced DNA rearrangements in rhabdoid tumor cells. Ectopic
      expression of PGBD5 in primary immortalized human cells was sufficient to promote
      cell transformation in vivo. This activity required specific catalytic residues
      in the PGBD5 transposase domain as well as end-joining DNA repair and induced
      structural rearrangements with PSS breakpoints. These results define PGBD5 as an
      oncogenic mutator and provide a plausible mechanism for site-specific DNA
      rearrangements in childhood and adult solid tumors.

PMID- 28504705
TI  - Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of
      stem cell properties.
AB  - The epidermis is maintained by multiple stem cell populations whose progeny
      differentiate along diverse, and spatially distinct, lineages. Here we show that
      the transcription factor Gata6 controls the identity of the previously
      uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream
      transcription factor network that specifies a lineage switch between sebocytes
      and SD cells. During wound healing differentiated Gata6+ cells migrate from the
      SD into the interfollicular epidermis and dedifferentiate, acquiring the ability
      to undergo long-term self-renewal and differentiate into a much wider range of
      epidermal lineages than in undamaged tissue. Our data not only demonstrate that
      the structural and functional complexity of the junctional zone is regulated by
      Gata6, but also reveal that dedifferentiation is a previously unrecognized
      property of post-mitotic, terminally differentiated cells that have lost contact
      with the basement membrane. This resolves the long-standing debate about the
      contribution of terminally differentiated cells to epidermal wound repair.

PMID- 28504708
TI  - Receptor oligomerization guides pathway choice between proteasomal and autophagic
      degradation.
AB  - Abnormal or aggregated proteins have a strong cytotoxic potential and are
      causative for human disorders such as Alzheimer's, Parkinson's, Huntington's
      disease and amyotrophic lateral sclerosis. If not restored by molecular
      chaperones, abnormal proteins are typically degraded by proteasomes or eliminated
      by selective autophagy. The discovery that both pathways are initiated by
      substrate ubiquitylation but utilize different ubiquitin receptors incited a
      debate over how pathway choice is achieved. Here, we demonstrate in yeast that
      pathway choice is made after substrate ubiquitylation by competing ubiquitin
      receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)
      binding modules. Proteasome pathway receptors bind ubiquitin moieties more
      efficiently, but autophagy receptors gain the upper hand following substrate
      aggregation and receptor bundling. Indeed, by using sets of modular artificial
      receptors harbouring identical ubiquitin-binding modules we found that
      proteasome/autophagy pathway choice is independent of the ubiquitin-binding
      properties of the receptors but largely determined by their oligomerization
      potentials. Our work thus suggests that proteasomal degradation and selective
      autophagy are two branches of an adaptive protein quality control pathway, which
      uses substrate ubiquitylation as a shared degradation signal.

PMID- 28504706
TI  - The mitochondrial respiratory chain is essential for haematopoietic stem cell
      function.
AB  - Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype,
      which is required for maintenance of stemness; however, whether mitochondrial
      respiration is required to maintain HSC function is not known. Here we report
      that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein
      (RISP) in fetal mouse HSCs allows them to proliferate but impairs their
      differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs
      displayed impaired respiration resulting in a decreased NAD+/NADH ratio. RISP
      null fetal HSCs and progenitors exhibited an increase in both DNA and histone
      methylation associated with increases in 2-hydroxyglutarate (2HG), a metabolite
      known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs
      also impaired respiration resulting in loss of quiescence concomitant with severe
      pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal
      HSC proliferation, but essential for fetal HSC differentiation and maintenance of
      adult HSC quiescence.

PMID- 28504703
TI  - Polygenic transmission disequilibrium confirms that common and rare variation act
      additively to create risk for autism spectrum disorders.
AB  - Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo
      variation. We aimed to clarify the influence of polygenic risk for ASD and to
      identify subgroups of ASD cases, including those with strongly acting de novo
      variants, in which polygenic risk is relevant. Using a novel approach called the
      polygenic transmission disequilibrium test and data from 6,454 families with a
      child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater
      educational attainment is over-transmitted to children with ASD. These findings
      hold independent of proband IQ. We find that polygenic variation contributes
      additively to risk in ASD cases who carry a strongly acting de novo variant.
      Lastly, we show that elements of polygenic risk are independent and differ in
      their relationship with phenotype. These results confirm that the genetic
      influences on ASD are additive and suggest that they create risk through at least
      partially distinct etiologic pathways.

PMID- 28504707
TI  - Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated
      protein translation.
AB  - Advances in genomic profiling present new challenges of explaining how changes in
      DNA and RNA are translated into proteins linking genotype to phenotype. Here we
      compare the genome-scale proteomic and transcriptomic changes in human primary
      haematopoietic stem/progenitor cells and erythroid progenitors, and uncover
      pathways related to mitochondrial biogenesis enhanced through post
      transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are
      selectively regulated through protein translation during erythroid specification.
      Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to
      elevated histone acetylation, deregulated gene expression, and defective
      mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced
      to promote translation of mitochondria-associated transcripts through TOP-like
      motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1
      specifically impairs erythropoiesis in vitro and in vivo. Our studies support a
      mechanism for post-transcriptional control of erythroid mitochondria and may have
      direct relevance to haematologic defects associated with mitochondrial diseases
      and ageing.

PMID- 28504709
TI  - Food security is related to adult type 2 diabetes control over time in a United
      States safety net primary care clinic population.
AB  - BACKGROUND/OBJECTIVES: Successful Type 2 diabetes management requires adopting a
      high nutrient-density diet made up of food items that both meet dietary needs and
      preferences and can be feasibly obtained on a regular basis. However, access to
      affordable, nutrient-dense foods often is lacking in poorer neighbourhoods.
      Therefore, low food security should directly impair glucose control, even when
      patients have full access to and utilize comprehensive medical management. The
      present study sought to determine whether food security is related longitudinally
      to glucose control, over-and-above ongoing medication management, among Type 2
      diabetes patients receiving comprehensive care at a Midwestern multi-site
      federally qualified health centre (FQHC). SUBJECTS/METHODS: In this longitudinal
      observational study, we completed a baseline assessment of patients' food
      security (using the US Household Food Security Module), demographics (via Census
      items), and diabetes history/management (using a structured clinical encounter
      form) when patients began receiving diabetes care at the health centre. We then
      recorded those patients' A1C levels several times during a 24-month follow-up
      period. Three hundred and ninety-nine patients (56% with low food security) had a
      baseline A1c measurement; a subsample of 336 (median age=52 years; 56% female;
      60% Hispanic, 27% African American, and 9% White) also had at least one follow-up
      A1c measurement. RESULTS: Patients with lower (vs higher) food security were more
      likely to be on insulin and have higher A1c levels at baseline. Moreover, the
      disparity in glucose control by food security status persisted throughout the
      next 2 years. CONCLUSIONS: Although results were based on one multi-site FQHC,
      potentially limiting their generalizability, they seem to suggest that among Type
      2 diabetes patients, low food security directly impairs glucose control-even when
      patients receive full access to comprehensive medical management-thereby
      increasing their long-term risks of high morbidity, early mortality, and high
      health-care utilization and cost.

PMID- 28504710
TI  - A1 beta-casein milk protein and other environmental pre-disposing factors for
      type 1 diabetes.
AB  - Globally type 1 diabetes incidence is increasing. It is widely accepted that the
      pathophysiology of type 1 diabetes is influenced by environmental factors in
      people with specific human leukocyte antigen haplotypes. We propose that a
      complex interplay between dietary triggers, permissive gut factors and
      potentially other influencing factors underpins disease progression. We present
      evidence that A1 beta-casein cows' milk protein is a primary causal trigger of
      type 1 diabetes in individuals with genetic risk factors. Permissive gut factors
      (for example, aberrant mucosal immunity), intervene by impacting the gut's
      environment and the mucosal barrier. Various influencing factors (for example,
      breastfeeding duration, exposure to other dietary triggers and vitamin D) modify
      the impact of triggers and permissive gut factors on disease. The power of the
      dominant trigger and permissive gut factors on disease is influenced by timing,
      magnitude and/or duration of exposure. Within this framework, removal of a
      dominant dietary trigger may profoundly affect type 1 diabetes incidence. We
      present epidemiological, animal-based, in vitro and theoretical evidence for A1
      beta-casein and its beta-casomorphin-7 derivative as dominant causal triggers of
      type 1 diabetes. The effects of ordinary milk containing A1 and A2 beta-casein
      and milk containing only the A2 beta-casein warrant comparison in prospective
      trials.

PMID- 28504711
TI  - The stabilizing effect of an oligomeric proanthocyanidin on red blood cell
      membrane structure of poorly controlled Type II diabetes.
AB  - Type II diabetes (T2D) is a pandemic characterized by pathological circulating
      inflammatory markers, high-glucose levels and oxidative stress. The hematological
      system is especially vulnerable to these aberrant circulating molecules, and
      erythrocytes (RBCs) show aberrant rheology properties, owing to the direct
      contact with these molecules. Pathological levels of circulating inflammatory
      markers in T2D therefore have a direct effect on the molecular and cellular
      structure of RBCs. Previous research has suggested that antioxidants may reduce
      oxidative stress that results from the pathological inflammatory markers.
      Particularly, polyphenol antioxidants like oligomeric proanthocyanidins (OPCs)
      may act as a hydroxyl mopping agent, and may have a positive effect on the
      deformability and membrane protein structure of RBCs from T2D. In this paper, we
      look at the effect of one such agent, Pinus massoniana bark extract (standardized
      to 95% oligomeric proanthicyanidins), on the RBC membrane structures and RBC
      shape changes of T2D, after laboratory exposure at physiological levels. Our
      methods of choice were atomic force microscopy and scanning electron microscopy
      to study RBC elasticity and ultrastructure. Results showed that in our hands,
      this OPC could change both the eryptotic nature of the RBCs, as viewed with
      scanning electron microscopy, as well as the elasticity. We found a significant
      difference in variation between the elasticity measurement values between the
      RBCs before and after OPC exposure (P-value <0.0001). In conclusion, the data
      from both these techniques therefore suggest that OPC usage might contribute to
      the improvement of RBC functioning.

PMID- 28504712
TI  - Flavonoid intake is inversely associated with obesity and C-reactive protein, a
      marker for inflammation, in US adults.
AB  - Recent studies have demonstrated the importance of flavonoid intake and disease
      risk, however the association between flavonoid intake and obesity has not been
      evaluated in a nationally representative sample of US adults. The objective of
      the study was to evaluate the association between flavonoid consumption and
      established risk factors for obesity and obesity-related inflammation. Data from
      a nationally representative sample of 9551 adults who participated in the 2005
      2008 National Health and Nutrition Examination Survey (NHANES) were analyzed.
      Flavonoid consumption was inversely associated with obesity in both men and women
      in multivariate models. Adults in the highest quartile of flavonoid intake had
      significantly lower body mass index and waist circumference than those in the
      lowest quartile of flavonoid intake (P<0.03 and P<0.04, respectively), and
      flavonoid intake was inversely related to C-reactive protein levels in women (p
      trend, 0.01). These findings support a growing body of laboratory evidence that
      flavonoid consumption may be beneficial for disease prevention.

PMID- 28504714
TI  - Cytoplasmic translocation of MTA1 coregulator promotes de-repression of SGK1
      transcription in hypoxic cancer cells.
AB  - Chromatin remodeling factor metastatic tumor protein 1 (MTA1), one of the most
      upregulated oncogene in human cancer, has an important role in gene expression,
      cell survival and promoting hypoxic response. Successful cancer progression is
      dependent on the ability of cells to utilize its survival pathways for adapting
      to hypoxic microenvironment. Although MTA1 is a stress-responsive gene, but
      whether hypoxia modulates its function and its role in engaging other core stress
      responsive survival pathway(s) remains unknown. Here we have discovered that MTA1
      is a novel corepressor of serum and glucocorticoid-inducible kinase 1 (SGK1).
      Surprisingly, this regulatory corepressive function of MTA1 is lost under
      hypoxia, allowing upregulation of SGK1 expression and engaging the MTA1-SGK1 axis
      for the benefit of the cell survival. The underlying mechanism of the noticed
      stimulation of SGK1 expression by hypoxia includes de-repression of SGK1
      transcription because of hypoxia-triggered nucleus-to-cytoplasmic translocation
      of MTA1. In addition, the newly recognized cytoplasmic translocation of MTA1 was
      dependent on the chaperoning function of heat shock protein 90 (HSP90) and co
      accompanied by the formation of MTA1, HSP90 and HIF1alpha complex under hypoxic
      condition but not under normoxic condition. Hypoxia-triggered redistribution of
      MTA1, SGK1 upregulation and cell survival functions were compromised by a
      pharmacological SGK1 inhibitor. In summary, for the first time, we report MTA1
      regulation of SGK1 expression, hypoxia-dependent MTA1 translocation to the
      cytoplasm and de-repression of SGK1 transcription. These findings illustrate how
      cancer cells utilize a chromatin remodeling factor to engage a core survival
      pathway to support its cancerous phenotypes, and reveal new facets of MTA1-SGK1
      axis by a physiologic signal in cancer progression.

PMID- 28504713
TI  - Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage
      response genes in thyroid cancer.
AB  - The proto-oncogene PTTG and its binding partner PBF have been widely studied in
      multiple cancer types, particularly thyroid and colorectal, but their combined
      role in tumourigenesis is uncharacterised. Here, we show for the first time that
      together PTTG and PBF significantly modulate DNA damage response (DDR) genes,
      including p53 target genes, required to maintain genomic integrity in thyroid
      cells. Critically, DDR genes were extensively repressed in primary thyrocytes
      from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG
      overexpression. Irradiation exposure to amplify p53 levels further induced
      significant repression of DDR genes in Bi-Tg thyrocytes (P=2.4 * 10-4) compared
      with either PBF- (P=1.5 * 10-3) or PTTG-expressing thyrocytes (P=NS). Consistent
      with this, genetic instability was greatest in Bi-Tg thyrocytes with a mean
      genetic instability (GI) index of 35.8+/-2.6%, as well as significant induction
      of gross chromosomal aberrations in thyroidal TPC-1 cells following
      overexpression of PBF and PTTG. We extended our findings to human thyroid cancer
      using TCGA data sets (n=322) and found striking correlations with PBF and PTTG
      expression in well-characterised DDR gene panel RNA-seq data. In addition,
      genetic associations and transient transfection identified PBF as a downstream
      target of the receptor tyrosine kinase-BRAF signalling pathway, emphasising a
      role for PBF as a novel component in a pathway well described to drive neoplastic
      growth. We also showed that overall survival (P=1.91 * 10-5) and disease-free
      survival (P=4.9 * 10-5) was poorer for TCGA patients with elevated tumoural
      PBF/PTTG expression and mutationally activated BRAF. Together our findings
      indicate that PBF and PTTG have a critical role in promoting thyroid cancer that
      is predictive of poorer patient outcome.

PMID- 28504715
TI  - Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing
      and contributes to the suppression of cancer development.
AB  - The contribution of RNA processing to tumorigenesis is understudied. Here, we
      report that the human RNA debranching enzyme (hDBR1), when inappropriately
      regulated, induces oncogenesis by causing RNA processing defects, for example,
      splicing defects. We found that wild-type p53 and hypoxia-inducible factor 1 co
      regulate hDBR1 expression, and insufficient hDBR1 leads to a higher rate of exon
      skipping. Transcriptomic sequencing confirmed the effect of hDBR1 on RNA
      splicing, and metabolite profiling supported the observation that neoplasm is
      triggered by a decrease in hDBR1 expression both in vitro and in vivo. Most
      importantly, when modulating the expression of hDBR1, which was found to be
      generally low in malignant human tissues, higher expression of hDBR1 only
      affected exon-skipping activity in malignant cells. Together, our findings
      demonstrate previously unrecognized regulation and functions of hDBR1, with
      immediate clinical implications regarding the regulation of hDBR1 as an effective
      strategy for combating human cancer.

PMID- 28504716
TI  - VEGFA links self-renewal and metastasis by inducing Sox2 to repress miR-452,
      driving Slug.
AB  - Cancer stem cells (CSC) appear to have increased metastatic potential, but
      mechanisms underlying this are poorly defined. Here we show that VEGFA induction
      of Sox2 promotes EMT and tumor metastasis. In breast lines and primary cancer
      culture, VEGFA rapidly upregulates SOX2 expression, leading to SNAI2 induction,
      EMT, increased invasion and metastasis. We show Sox2 downregulates miR-452, which
      acts as a novel metastasis suppressor to directly target the SNAI2 3'
      untranslated region (3'-UTR). VEGFA stimulates Sox2- and Slug-dependent cell
      invasion. VEGFA increases lung metastasis in vivo, and this is abrogated by miR
      452 overexpression. Furthermore, SNAI2 transduction rescues metastasis
      suppression by miR-452. Thus, in addition to its angiogenic action, VEGFA
      upregulates Sox2 to drive stem cell expansion, together with miR-452 loss and
      Slug upregulation, providing a novel mechanism whereby cancer stem cells acquire
      metastatic potential. Prior work showed EMT transcription factor overexpression
      upregulates CSC. Present work indicates that stemness and metastasis are a two
      way street: Sox2, a major mediator of CSC self-renewal, also governs the
      metastatic process.

PMID- 28504717
TI  - Fibulin-3 promotes muscle-invasive bladder cancer.
AB  - Urothelial carcinoma is the most common type of bladder cancer and can be
      categorized as either non-muscle-invasive (Ta-T1) or muscle-invasive (?T2). The
      majority of bladder cancers are non-muscle-invasive at presentation; however, the
      recurrence rate for these tumors is high and a subset can progress to T2. In this
      study, we aimed to identify genes differentially expressed between T1 vs T2
      bladder cancer to identify key regulators of bladder cancer progression and/or
      invasion. We performed RNA-Seq on T1 and T2 bladder cancer tissues and used
      publicly available bladder cancer profiling studies to prioritize differentially
      expressed genes for validation and functional assessment. This integrative
      approach nominated an extracellular matrix glycoprotein, fibulin-3 (FBLN3, also
      known as EFEMP1), as being highly expressed in T2 vs T1 bladder cancer and
      aggressive vs indolent disease. We confirmed the overexpression of fibulin-3 in
      ?T2 vs non-muscle-invasive bladder cancer (NMIBC) by quantitative reverse
      transcriptase-PCR. Consistent with these findings, fibulin-3 expression level
      correlated with the invasive ability of several bladder cancer cell lines and
      modulation of fibulin-3 expression directly affected invasion. Fibulin-3
      knockdown in bladder cancer cells decreased the incidence of MIBCs in a murine
      orthotopic bladder cancer model and decreased the expression of insulin-like
      growth factor-binding protein-5 (IGFBP5). Restoring IGFBP5 in these cells rescued
      their invasive and migratory potential. These results indicate that fibulin-3
      serves as a pro-invasive factor in bladder cancer, which may be mediated through
      modulation of IGFBP5 expression. This also suggests fibulin-3 and IGFBP5 may have
      potential as biomarkers of aggressive bladder cancer or therapeutic targets.

PMID- 28504719
TI  - Novel MYC-driven medulloblastoma models from multiple embryonic cerebellar cells.
AB  - Group3 medulloblastoma (MBG3) that predominantly occur in young children are
      usually associated with MYC amplification and/or overexpression, frequent
      metastasis and a dismal prognosis. Physiologically relevant MBG3 models are
      currently lacking, making inferences related to their cellular origin thus far
      limited. Using in utero electroporation, we here report that MBG3 mouse models
      can be developed in situ from different multipotent embryonic cerebellar
      progenitor cells via conditional expression of Myc and loss of Trp53 function in
      several Cre driver mouse lines. The Blbp-Cre driver that targets embryonic neural
      progenitors induced tumors exhibiting a large-cell/anaplastic histopathology
      adjacent to the fourth ventricle, recapitulating human MBG3. Enforced co
      expression of luciferase together with Myc and a dominant-negative form of Trp53
      revealed that GABAergic neuronal progenitors as well as cerebellar granule cells
      give rise to MBG3 with their distinct growth kinetics. Cross-species gene
      expression analysis revealed that these novel MBG3 models shared molecular
      characteristics with human MBG3, irrespective of their cellular origin. We here
      developed MBG3 mouse models in their physiological environment and we show that
      oncogenic insults drive this MB subgroup in different cerebellar lineages rather
      than in a specific cell of origin.

PMID- 28504718
TI  - A tumor suppressor role for C/EBPalpha in solid tumors: more than fat and blood.
AB  - The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays
      a critical role during embryogenesis and is thereafter required for homeostatic
      glucose metabolism, adipogenesis and myeloid development. Its ability to regulate
      the expression of lineage-specific genes and induce growth arrest contributes to
      the terminal differentiation of several cell types, including hepatocytes,
      adipocytes and granulocytes. CEBPA loss of-function mutations contribute to the
      development of ~10% of acute myeloid leukemia (AML), stablishing a tumor
      suppressor role for C/EBPalpha. Deregulation of C/EBPalpha expression has also
      been reported in a variety of additional human neoplasias, including liver,
      breast and lung cancer. However, functional CEBPA mutations have not been found
      in solid tumors, suggesting that abrogation of C/EBPalpha function in non
      hematopoietic tissues is regulated by alternative mechanisms. Here we review the
      function of C/EBPalpha in solid tumors and focus on the molecular mechanisms
      underlying its tumor suppressive role.

PMID- 28504720
TI  - A clinical drug library screen identifies clobetasol propionate as an NRF2
      inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer.
AB  - The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor
      2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2
      activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers,
      suggesting that NRF2 inhibition could be a promising therapeutic strategy.
      However, no potent NRF2 inhibitors are clinically available to date. To develop
      potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical
      compounds and determined clobetasol propionate (CP) as the most potent NRF2
      inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted beta
      TrCP-dependent degradation of NRF2 in a glucocorticoid receptor- and a glycogen
      synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative
      stress and strongly suppressed the anchorage-independent growth of tumors with
      KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in
      combination with rapamycin strongly inhibited the in vitro and in vivo growth of
      tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently
      observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for
      cancers with high NRF2 activity. We also proposed that the use CP and rapamycin
      in combination could be a potential therapeutic strategy for tumors harboring
      both KEAP1 and LKB1 mutations.

PMID- 28504721
TI  - Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant
      phenotype and temozolomide chemoresistance in glioblastoma.
AB  - Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma
      (GBM) progression, and many fusion genes are strong driver mutations in neoplasia
      and are involved in tumorigenesis. However, the ability of fusion genes to be
      transduced by exosomes is unknown. We characterized exosomes from GBM cells
      harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined
      the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic
      secretions and showed that ZM exosomes are internalized by the recipient cells.
      In addition, we studied the effect of ZM exosome-mediated intercellular
      communication in the GBM microenvironment. MET proto-oncogene expression was
      higher in ZM exosomes. Moreover, phosphorylated MET was detected only in ZM
      exosomes and not in exosomes released by non-ZM fusion GBM cells. ZM exosomes
      transferred to non-ZM fusion GBM cells and normal human astrocytes altered gene
      expression and induced epithelial-mesenchymal transition. The uptake of ZM
      exosomes also induced an exosome-dependent phenotype defined by GBM cell
      migration and invasion, neurosphere growth and angiogenesis. In addition, ZM
      exosomes conferred temozolomide resistance to the GBM cells, and exosome-derived
      ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient
      cells within the GBM microenvironment. Our findings show that exosomes mediate
      the aggressive character of GBM and demonstrate the role of ZM fusion in the
      exacerbation of this effect. These findings have possible implications for the
      foundation of gene fusion-based therapy for managing GBM.

PMID- 28504722
TI  - Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing
      mitochondrial turnover.
AB  - Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular
      carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx)
      has critical role in the induction of carcinogenesis. Several studies have shown
      that thyroid hormone (TH) suppresses HCC development and protects hepatocytes
      from HBx-induced damage, thus it is of interest to examine whether TH can protect
      hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice
      with or without TH, we confirmed the protective effects of TH on HBx-induced
      hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species
      (ROS) inflicted DNA damage. We further found that TH induced biogenesis of
      mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously,
      consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using
      microarray data analysis, this protective effect of TH was found to be mediated
      via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn,
      activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx
      protein and trigger selective mitophagy. The pathological significance of the
      TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in
      expression of both TR and PINK1 in matched HCC tumor tissues and negatively
      correlated with aggressive progression of cancer and poor prognosis. Our data
      indicate that TH/PINK1/Parkin pathway has a critical role in protecting
      hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting
      therapeutic derivatives of TH facilitating prevention or therapy of steatosis
      have been identified. Furthermore, our proof-of-concept experiments suggest that
      application of T3 constitutes an effective novel therapeutic or preventive option
      for HCC. Thus, the utilization of the agonists of TRs could be the meaningful
      strategy in liver relative diseases, ranging from simple hepatic steatosis to
      HCC.

PMID- 28504723
TI  - CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine
      remodeling via TNF-alpha.
AB  - Impaired learning and cognitive function often occurs during systemic infection
      or inflammation. Although activation of the innate immune system has been linked
      to the behavioral and cognitive effects that are associated with infection, the
      underlying mechanisms remain poorly understood. Here we mimicked viral immune
      activation with poly(I:C), a synthetic analog of double-stranded RNA, and
      longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons
      in the mouse primary motor cortex using two-photon microscopy. We found that
      peripheral immune activation caused dendritic spine loss, impairments in learning
      dependent dendritic spine formation and deficits in multiple learning tasks in
      mice. These observed synaptic alterations in the cortex were mediated by
      peripheral-monocyte-derived cells and did not require microglial function in the
      central nervous system. Furthermore, activation of CX3CR1highLy6Clow monocytes
      impaired motor learning and learning-related dendritic spine plasticity through
      tumor necrosis factor (TNF)-alpha-dependent mechanisms. Taken together, our
      results highlight CX3CR1high monocytes and TNF-alpha as potential therapeutic
      targets for preventing infection-induced cognitive dysfunction.

PMID- 28504726
TI  - Multiple wavelength stabilization on a single optical cavity using the offset
      sideband locking technique.
AB  - We implemented a compact, robust, and stable device for simultaneous frequency
      stabilization of lasers with different wavelengths used for the cooling and
      trapping of Yb atoms in an optical lattice clock. The lasers at 399, 556, and 759
      nm are locked to a single ultra-stable cavity using the offset sideband locking
      technique, a modified version of the Pound-Drever-Hall method. For the most
      demanding stabilization here, the 556 nm laser, this system exhibits a 300 Hz
      linewidth for an integration time of 80 ms. We observed a long-term drift of less
      than 20 kHz per day at 759 nm that is suitable for operating the lattice laser
      with a light shift uncertainty below 1*10<sup>-18</sup>. We successfully tested
      the system for operating the clock during a typical working day by simultaneously
      locking the three lasers to the cavity.

PMID- 28504727
TI  - Reduced-symmetry LMA rod-type fiber for enhanced higher-order mode
      delocalization.
AB  - We present a novel design of a micro-structured large-pitch, large-mode-area
      (LMA) asymmetric rod-type fiber. By reducing the cladding symmetry through six
      high-refractive index germanium-doped silica inclusions, the fiber features
      strong higher-order mode (HOM) delocalization, leading to a potentially enhanced
      preferential gain for the fundamental mode in active fibers. In addition, high
      resolution spatially and spectrally (S<sup>2</sup>) resolved mode analysis
      measurements confirm HOM contributions below 1% and LP<sub>1m</sub>-like HOM
      contributions below the detection limit. This proposed fiber design enables
      single-mode operation, with near-diffraction-limited beam quality of
      M<sup>2</sup>=1.3 and an effective mode area of 2560  MUm<sup>2</sup> at 1064 nm.
      This design opens new insights into improving the threshold-like onset of modal
      instabilities in high-power fiber lasers and fiber amplifiers by efficiently
      suppressing LP<sub>11</sub> modes.

PMID- 28504728
TI  - Scalable Fourier transform system for instantly structured illumination in
      lithography.
AB  - We report the development of a unique scalable Fourier transform 4-f system for
      instantly structured illumination in lithography. In the 4-f system, coupled with
      a 1-D grating and a phase retarder, the +/-1st order of diffracted light from the
      grating serve as coherent incident sources for creating interference patterns on
      the image plane. By adjusting the grating and the phase retarder, the
      interference fringes with consecutive frequencies, as well as their orientations
      and phase shifts, can be generated instantly within a constant interference area.
      We demonstrate that by adapting this scalable Fourier transform system into
      lithography, the pixelated nano-fringe arrays with arbitrary frequencies and
      orientations can be dynamically produced in the photoresist with high variation
      resolution, suggesting its promising application for large-area functional
      materials based on space-variant nanostructures in lithography.

PMID- 28504725
TI  - Metformin ameliorates core deficits in a mouse model of fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum
      disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression,
      leading to hyperactivation of ERK and mTOR signaling upstream of mRNA
      translation. Here we show that metformin, the most widely used drug for type 2
      diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK
      signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is
      a potential FXS therapeutic.

PMID- 28504729
TI  - High-precision micro-displacement optical-fiber sensor based on surface plasmon
      resonance.
AB  - We propose and demonstrate a novel optical-fiber micro-displacement sensor based
      on surface plasmon resonance (SPR) by fabricating a Kretschmann configuration on
      graded-index multimode fiber (GIMMF). We employ a single-mode fiber to change the
      radial position of the incident beam as the displacement. In the GIMMF, the angle
      between the light beam and fiber axis, which is closely related to the resonance
      angle, is changed by the displacement; thus, the resonance wavelength of the
      fiber SPR shifts. This micro-displacement fiber sensor has a wide detection range
      of 0-25 MUm, a high sensitivity with maximum up to 10.32 nm/MUm, and a nanometer
      resolution with minimum to 2 nm, which transcends almost all of other optical
      fiber micro-displacement sensors. In addition, we also research that increasing
      the fiber polishing angle or medium refractive index can improve the sensitivity.
      This micro-displacement sensor will have a great significance in many industrial
      applications and provide a neoteric, rapid, and accurate optical measurement
      method in micro-displacement.

PMID- 28504730
TI  - Non-phase unwrapping interferometric approach for a real-time in-plane rotation
      measurement.
AB  - This Letter proposes a novel interferometric approach for the in-plane rotation
      measurement. With a simple and compact measurement system, the rotation angle and
      its direction can be determined simultaneously in real time by applying the
      spatial carrier frequency. Besides, the phase unwrapping process is not required
      for the angular evaluation, which simplifies the data processing procedure.
      Theoretically, the relationship between the in-plane rotation and the phase
      change distribution has been deduced to demonstrate the possibility of this
      interferometric method. Practically, the preliminary experiments have been
      carried out to verify the feasibility of this approach and quantify the
      measurement accuracy.

PMID- 28504724
TI  - Single-cell transcriptomics uncovers distinct molecular signatures of stem cells
      in chronic myeloid leukemia.
AB  - Recent advances in single-cell transcriptomics are ideally placed to unravel
      intratumoral heterogeneity and selective resistance of cancer stem cell (SC)
      subpopulations to molecularly targeted cancer therapies. However, current single
      cell RNA-sequencing approaches lack the sensitivity required to reliably detect
      somatic mutations. We developed a method that combines high-sensitivity mutation
      detection with whole-transcriptome analysis of the same single cell. We applied
      this technique to analyze more than 2,000 SCs from patients with chronic myeloid
      leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs,
      including the identification of a subgroup of CML-SCs with a distinct molecular
      signature that selectively persisted during prolonged therapy. Analysis of
      nonleukemic SCs from patients with CML also provided new insights into cell
      extrinsic disruption of hematopoiesis in CML associated with clinical outcome.
      Furthermore, we used this single-cell approach to identify a blast-crisis
      specific SC population, which was also present in a subclone of CML-SCs during
      the chronic phase in a patient who subsequently developed blast crisis. This
      approach, which might be broadly applied to any malignancy, illustrates how
      single-cell analysis can identify subpopulations of therapy-resistant SCs that
      are not apparent through cell-population analysis.

PMID- 28504732
TI  - Automated technique to inscribe reproducible long-period gratings using a
      CO<sub>2</sub> laser splicer.
AB  - We propose a technique to inscribe long period gratings (LPGs) in standard single
      mode fibers (SSMFs). The proposed method uses a commercial CO<sub>2</sub> splicer
      that allows for the rotation of the fiber during laser irradiation, enabling a
      uniform exposure around the fiber. LPGs inscribed in SSMFs with different periods
      are presented. Gratings can be reproduced with a maximum difference between
      resonant wavelength values of less than 1 nm. Furthermore, it is possible to
      inscribe gratings with attenuation dips of -25  dB while at the same time
      obtaining polarization-dependent losses as low as 2 dB.

PMID- 28504731
TI  - Non-reciprocal geometric phase in nonlinear frequency conversion.
AB  - We describe analytically and numerically the geometric phase arising from
      nonlinear frequency conversion and show that such a phase can be made non
      reciprocal by momentum-dependent photonic transition. Such non-reciprocity is
      immune to the shortcomings imposed by dynamic reciprocity in Kerr and Kerr-like
      devices. We propose a simple and practical implementation, requiring only a
      single waveguide and one pump, while the geometric phase is controllable by the
      pump and promises robustness against fabrication errors.

PMID- 28504733
TI  - Uncloaking diffusive-light invisibility cloaks by speckle analysis.
AB  - Within the range of validity of the stationary diffusion equation, an ideal
      diffusive-light invisibility cloak can make an arbitrary macroscopic object
      hidden inside of the cloak indistinguishable from the surroundings for all
      colors, polarizations, and directions of incident visible light. However, the
      diffusion equation for light is an approximation which becomes exact only in the
      limit of small coherence length. Thus, one expects that the cloak can be revealed
      by illumination with coherent light. The experiments presented here show that the
      cloaks are robust in the limit of large coherence length but can be revealed by
      analysis of the speckle patterns under illumination with partially coherent
      light. Experiments on cylindrical core-shell cloaks and corresponding theory are
      in good agreement.

PMID- 28504734
TI  - Stochastic mirage phenomenon in a random medium.
AB  - In the framework of geometric optics, we consider the problem of characterizing
      the ray trajectory in a random medium with a mean refractive index gradient. Such
      a gradient results in the mirage phenomenon where an object's observed location
      is displaced from its actual location. We derive formulas for the mean ray path
      in both the situation of isotropic stochastic fluctuations and an important
      anisotropic case. For the isotropic model, the mean squared displacement is also
      given by a simple formula. Our results could be useful for applications involving
      the propagation of electromagnetic waves through the atmosphere, where larger
      scale mean gradients and smaller-scale stochastic fluctuations are both present.

PMID- 28504735
TI  - High sensitivity narrowband wavelength mid-infrared detection at room
      temperature.
AB  - We report an upconversion experiment using an orientation-patterned gallium
      arsenide (OP-GaAs) crystal to detect small mid-infrared signals on an InGaAs
      avalanche photodiode. A conversion efficiency up to 20% with a nonpolarized
      pulsed fiber pump is demonstrated. Our uncooled setup is favorably compared in
      terms of noise equivalent power, dynamic range, and response time to
      cryogenically cooled HgCdTe detectors. Its dependence on the polarization of both
      the pump and signal beams is also investigated.

PMID- 28504736
TI  - Third-harmonic blue light generation from Kerr clustered combs and dispersive
      waves.
AB  - We demonstrated the deterministic generation of blue light emission (438 nm) via
      the third-harmonic process from an infrared pump by carefully engineering the
      dispersion of a high-quality-factor whispering gallery mode microcavity. We
      present two different approaches to obtaining broad bandwidth light. One is based
      on a clustered comb and the other employs a dispersive wave, and a broad Kerr
      comb spanning a half-octave is obtained. This allowed frequency conversion over a
      broad bandwidth ranging from 438 to 612 nm. This approach will enable the
      development of micro-scale light sources and frequency converters for future
      optical processing.

PMID- 28504738
TI  - Photonics sensing at the thermodynamic limit.
AB  - We report a slow-light fiber Bragg grating strain sensor with a resolution
      limited by the extremely low thermodynamic phase fluctuations of the fiber. This
      was accomplished by using a short grating (4.5 mm) to enhance the thermal phase
      noise, an ultra-stable interrogation laser to lower the laser frequency noise,
      and a slow-light mode with a high group index (~533) to suppress all other noise
      sources. We demonstrate that in a similar but longer grating (21 mm), the phase
      noise is suppressed in inverse proportion to the square root of the length, in
      accordance with theory, leading to a strain resolution as low as 130 
      fepsilon/?Hz and a minimum detectable length of ~3*10<sup>-15</sup>  m at 1.5
      kHz.

PMID- 28504737
TI  - Multi-petawatt laser facility fully based on optical parametric chirped-pulse
      amplification.
AB  - We report on a multi-petawatt 3-cascaded all-optical parametric chirped-pulse
      amplification laser facility. The experimental results demonstrate that the
      maximum energy after the final amplifier and after the compressor is 168.7 J and
      91.1 J, respectively. The pulse width (FWHM) is 18.6 fs in full width at half
      maximum after optimization of pulse compression. Therefore, 4.9 PW peak power has
      been achieved for the laser facility. To the best of our knowledge, this is the
      highest peak power reported so far for an all-optical parametric chirped-pulse
      amplification facility, and a compressed pulse shorter than 20 fs is achieved in
      a PW-class laser facility for the first time.

PMID- 28504739
TI  - Miniature multicore optical fiber vibration sensor.
AB  - We demonstrate a compact and versatile interferometric vibration sensor that
      operates in reflection mode. To build the device, a short segment of symmetric
      strongly coupled multicore optical fiber (MCF) is fusion spliced to a single-mode
      optical fiber (SMF). One end of the MCF segment is cleaved and placed in a
      cantilever position. Due to the SMF-MCF configuration, only two supermodes are
      excited in the MCF. Vibrations induce cyclic bending of the MCF cantilever which
      results in periodic oscillations of the reflected interference spectrum. In our
      device, the MCF itself is the inertial mass. The frequency range where our device
      is sensitive can be easily tailored from a few hertz to several kilohertz through
      the cantilever dimensions.

PMID- 28504740
TI  - Nonresonant modes in plasmonic holey metasurfaces for the design of artificial
      flat lenses.
AB  - This Letter discusses nonresonant modes excited on holey metasurfaces and their
      influence on the properties of spoof plasmonic states supported by the
      metasurface when a second surface is placed in its proximity. We consider here a
      metallic surface with periodic holes drilled in it. The field excited on each
      hole is projected onto a set of nonresonant modes in order to discuss their
      relative relevance. While previous simpler models assumed only the presence of
      the fundamental mode, we show that the simultaneous presence of several modes
      occurs when the surface is placed next to a metallic plate. Therefore, higher
      order modes are responsible for the peculiar physical properties of wave
      propagation of spoof plasmons between two surfaces, which can lead to new
      gradient-index flat lenses for transceivers for space communications.

PMID- 28504741
TI  - Real-time acquisition of complex optical fields by binary amplitude modulation.
AB  - We describe, through simulations and experiments, a real-time wavefront
      acquisition technique using random binary amplitude masks and an iterative phase
      retrieval algorithm based on the Fresnel propagator. By using a digital
      micromirror device, it is possible to recover an unknown complex object by
      illuminating with this set of masks and simultaneously recording the resulting
      intensity patterns with a high-speed camera, making this technique suitable for
      dynamic applications.

PMID- 28504742
TI  - Study of the interaction between graphene and planar terahertz metamaterial with
      toroidal dipolar resonance.
AB  - A planar terahertz metamaterial consisting of square split ring resonators is
      proposed, and the excitation of toroidal dipolar resonance is demonstrated.
      Moreover, we theoretically investigate the strong interaction between graphene
      and toroidal dipolar resonance of the metamaterial. By varying its Fermi energy,
      the simulations show that graphene can actively modulate the transmission
      amplitude of toroidal dipolar resonance and even switch it off. The interaction
      of the toroidal dipolar resonance with monolayer graphene further highlights the
      ultrasensitive sensing characteristic of the planar metamaterial, which can be
      utilized for other graphene-like two-dimensional materials. These intriguing
      properties of the proposed metamaterial may have potential applications in
      terahertz modulators and ultrasensitive sensors.

PMID- 28504743
TI  - Accumulation-layer surface plasmons in transparent conductive oxides.
AB  - A rigorous analytical study of the eigenmodes supported by a charge accumulation
      layer within a transparent conductive oxide (TCO) is presented. The new class of
      surface plasmons termed accumulation-layer surface plasmons (ASPs) is introduced.
      Near resonance ASPs are tightly bound and display a vast effective index
      tunability that could be of great practical interest. The suppression of ASPs in
      the presence of epsilon-near zero regions is discussed.

PMID- 28504744
TI  - Degenerate cavity supporting more than 31 Laguerre-Gaussian modes.
AB  - Photons propagating in Laguerre-Gaussian modes have characteristic orbital
      angular momenta, which are fundamental optical degrees of freedom. The orbital
      angular momentum of light has potential application in high-capacity optical
      communication and even in quantum information processing. In this work, we
      experimentally construct a ring cavity with four lenses and four mirrors that is
      completely degenerate for Laguerre-Gaussian modes. By measuring the transmitted
      peaks and patterns of different modes, the ring cavity is shown to support more
      than 31 Laguerre-Gaussian modes. The constructed degenerate cavity opens a new
      way for using the unlimited resource of available angular momentum states
      simultaneously.

PMID- 28504745
TI  - 16  MHz wavelength-swept and wavelength-stepped laser architectures based on
      stretched-pulse active mode locking with a single continuously chirped fiber
      Bragg grating.
AB  - We demonstrate a novel high-speed and broadband laser architecture based on
      stretched pulse active mode locking that provides a wavelength-swept and
      wavelength-stepped output. The laser utilizes a single intracavity 8.3 meter
      chirped fiber Bragg grating to generate positive and negative dispersion, and can
      be operated with or without an intracavity fixed Fabry-Perot etalon to generate
      wavelength-swept and wavelength-stepped (frequency comb) outputs, respectively.
      Using a four-path delay line at the output, we achieved 16.3 MHz repetition rates
      and a 62 nm lasing bandwidth centered at 1550 nm. Single-sided double-pass
      coherence lengths of 1.25 mm for the wavelength-swept configuration and more than
      30 mm for the wavelength-stepped configuration were obtained. Relative intensity
      noise was measured to be better than -140  dB/Hz. The stretched-pulse mode-locked
      architecture utilizing long chirped fiber Bragg gratings offers a simple and
      compact design for a broadband wavelength-tuned output at unprecedented speeds,
      and can address the need for fast sources in applications such as optical
      ranging, imaging, and sensing.

PMID- 28504746
TI  - Ultrabroadband out-of-loop characterization of the carrier-envelope phase noise
      of an offset-free Er:fiber frequency comb.
AB  - Recent demonstrations of passively phase-locked fiber-based combs motivate
      broadband characterization of the noise associated with the stabilized carrier
      envelope offset frequency. In our study, we analyze the phase noise of a 100 MHz
      Er:fiber system in a wide range spanning from microhertz to the Nyquist
      frequency. An interferometric detection method enables analysis of the high
      frequency output of an f-to-2f interferometer. The dominant contribution of a
      broadband white noise floor at high frequencies attests quantum-limited
      performance. An out-of-loop measurement of the carrier-envelope phase reveals its
      jitter to be as low as 250 mrad when integrated over 12 orders of magnitude of
      the radio-frequency spectrum.

PMID- 28504747
TI  - Ultra-slow light propagation by self-induced transparency in ruby in the
      superhyperfine limit.
AB  - Self-induced transparency is reported for circularly polarized light in the
      R<sub>1</sub>(-3/2) line of a 30 ppm ruby (alpha
      Al<sub>2</sub>O<sub>3</sub>:Cr<sup>3+</sup>) at 1.7 K in a magnetic field of
      B||c=4.5  T. In such a field and temperature, a 30 ppm ruby is in the so-called
      superhyperfine limit resulting in a long phase memory time, T<sub>M</sub>=50 
      MUs, and a thousand-fold slower pulse propagation velocity of ~300  m/s was
      observed, compared to the ~300  km/s measured in the first observation of self
      induced transparency (SIT) ~50 years ago, that employed a ruby with a 500 ppm
      chromium concentration in zero field and at 4.2 K. To date, this is the slowest
      pulse propagation ever observed in a SIT experiment.

PMID- 28504748
TI  - Terahertz multilevel phase Fresnel lenses fabricated by laser patterning of
      silicon.
AB  - Multilevel phase Fresnel lenses (MPFLs) with a high numerical aperture for 0.58
      THz frequencies were developed. The components based on a monocrystalline silicon
      wafer are prepared by patterning by a high-speed industrial-scale laser direct
      writing (LDW) system. Two consistent series of the terahertz-MPFLs with phase
      quantization levels varying between 2 and the continuous kinoform shape for the
      focal lengths of 5 and 10 mm were produced employing inherent flexibility of the
      LDW fabrication process. The focusing performance was studied at the optimal 0.58
      THz frequency using a Gaussian beam profile and scanning 2D intensity
      distribution with a terahertz detector along the optical axis. The efficiency of
      the terahertz-MPFL was found to be dependent of the number of subzones. The
      position and orientation angles of the patterned plane of the silicon wafer were
      considered to reduce the effect of standing waves formation in the experiment.

PMID- 28504749
TI  - Designing ultrabroadband absorbers based on Bloch theorem and optical topological
      transition.
AB  - In this Letter, we propose a method to design ultrabroadband near-perfect
      absorbers, consisting of a periodic dielectric-metal multilayer. In the method,
      the Bloch theorem and optical topological transition (OTT) of iso-frequency
      surfaces are employed to manipulate the start and end of the near-perfect
      spectral absorption band, respectively. Moreover, we design and fabricate an
      ultrabroadband near-perfect absorber utilizing the proposed method. The average
      absorption of the designed absorber is ~95% in the focused visible and near
      infrared range (0.4-2 MUm). This omnidirectional and polarization-independent
      near-perfect absorber is promising for solar energy harvesting, emissivity
      control, and thermal imaging.

PMID- 28504750
TI  - Self-compression of femtosecond deep-ultraviolet pulses by filamentation in
      krypton.
AB  - We demonstrate self-compression of deep-ultraviolet (DUV) pulses by filamentation
      in krypton. In contrast to self-compression in the near-infrared, that in the DUV
      is associated with a red-shifted sub-pulse appearing in the pulse temporal
      profile. The achieved pulse width of 15 fs is the shortest among demonstrated sub
      mJ deep-ultraviolet pulses.

PMID- 28504751
TI  - Highly scalable femtosecond coherent beam combining demonstrated with 19 fibers.
AB  - Coherent beam combining in the femtosecond regime of a record number of 19 fibers
      is demonstrated. The interferometric phase measurement technique, particularly
      well suited to phase-lock a very large number of fibers, is successfully
      demonstrated in the femtosecond regime. A servo loop is implemented to control
      piezoelectric fiber stretchers for both phase and delay variation compensation.
      The residual phase errors are below lambda/60  rms. Nearly 50% of the total
      energy is contained in the far-field central lobe. After compression, we obtain a
      combined pulse width of 300 fs identical to the master oscillator pulse width.

PMID- 28504752
TI  - Large-scale nanostructured low-temperature solar selective absorber.
AB  - A large-scale nanostructured low-temperature solar selective absorber is
      demonstrated experimentally. It consists of a silicon dioxide thin film coating
      on a rough refractory tantalum substrate, fabricated based simply on self
      assembled, closely packed polystyrene nanospheres. Because of the strong light
      harvesting of the surface nanopatterns and constructive interference within the
      top silicon dioxide coating, our absorber has a much higher solar absorption
      (0.84) than its planar counterpart (0.78). Though its absorption is lower than
      that of commercial black paint with ultra-broad absorption, the greatly
      suppressed absorption/emission in the long range still enables a superior heat
      accumulation. The working temperature is as high as 196.3 degrees C under 7-sun
      solar illumination in ambient conditions-much higher than those achieved by the
      two comparables.

PMID- 28504753
TI  - Second-harmonic focusing by a nonlinear turbid medium via feedback-based
      wavefront shaping.
AB  - Scattering has usually been considered detrimental for optical focusing or
      imaging. Recently, more and more research has shown that strongly scattering
      materials can be utilized to focus coherent light by controlling or shaping the
      incident light. Here, purposeful focusing of second-harmonic waves, which are
      generated and scattered from nonlinear turbid media via feedback-based wavefront
      shaping, is presented. This Letter shows a flexible manipulation of both
      disordered linear and nonlinear scattering signals, indicating more controllable
      degrees of freedom for the description of turbid media. This technique also
      provides a possible way to an efficient transmission of nonlinear signal at a
      desired location in the form of a focal point or other patterns. With the
      combination of random nonlinear optics and wavefront shaping methods, more
      interesting applications can be expected in the future, such as nonlinear
      transmission matrix, multi-frequency imaging, and phase-matching-free nonlinear
      optics.

PMID- 28504754
TI  - Performance comparison of pseudo-inverse and maximum-likelihood estimators of
      Stokes parameters in the presence of Poisson noise for spherical design-based
      measurement structures.
AB  - Estimation of the Stokes vector from N>4 intensity measurements is usually
      performed with the pseudo-inverse (PI) estimator, which is optimal when the noise
      that corrupts the measurements is additive and Gaussian. In the presence of
      Poisson shot noise, the maximum-likelihood (ML) estimator is different from the
      PI estimator, but is more complex to implement since it is not closed-form. We
      compare in this Letter the precisions obtained with the ML and the PI estimators
      in the presence of Poisson noise when using measurement structures based on
      spherical designs. We show that, in this case, the gain in precision brought by
      the ML estimator is real but modest, so that in applications where processing
      speed is an issue, the PI estimator can be considered sufficient. This result is
      important in the choice of the inversion strategy for Stokes polarimetry.

PMID- 28504755
TI  - Resolving 1 million sensing points in an optimized differential time-domain
      Brillouin sensor.
AB  - A differential pulse-width pair (DPP) Brillouin distributed fiber sensor is
      implemented to achieve centimetric spatial resolution over distances of several
      kilometers. The presented scheme uses a scanning method in which the spectral
      separation between the two probe sidebands is kept constant, while the optical
      frequency of the pump is swept to scan the Brillouin spectral response.
      Experimental results show that this method avoids detrimental temporal
      distortions of the pump pulses, which in a standard implementation prevent the
      DPP method from operating over mid-to-long distances. Such a novel scanning
      procedure allows the resolving, for the first time in pure time-domain Brillouin
      sensors, of 1,000,000 sensing points, i.e., 1 cm spatial resolution over 10 km in
      a conventional acquisition time.

PMID- 28504756
TI  - Active modulation of the terahertz spectra radiated from two air plasmas.
AB  - A simple and energy-saving method has been proposed to actively modulate the
      spectra of terahertz (THz) waves radiated from two serial plasmas, which uses the
      background light to generate one plasma to make full use of the energy of the
      femtosecond laser. With this method, the modulation of the central frequency,
      spectral bandwidth, and spectral profile of the output THz waves have been
      observed. The shifting of the amplitude dip has been manipulated by changing the
      distance of the two serial plasmas. The manipulation results agree with the ones
      simulated by the transition-Cherenkov model. This proposed method provides a
      useful tool for getting the modulated THz spectra that can be used in the THz
      remote sensing.

PMID- 28504757
TI  - Absolute frequency measurements of CHF<sub>3</sub> Doppler-free ro-vibrational
      transitions at 8.6  MUm.
AB  - We report on absolute measurements of saturated-absorption line-center
      frequencies of room-temperature trifluoromethane using a quantum cascade laser at
      8.6 MUm and the frequency modulation spectroscopy method. Absolute calibration of
      the laser frequency is obtained by direct comparison with a mid-infrared optical
      frequency comb synthesizer referenced to a radio-frequency Rb standard. Several
      sub-Doppler transitions falling in the upsilon<sub>5</sub> vibrational band are
      investigated at around 1158.9  cm<sup>-1</sup> with a fractional frequency
      precision of 8.6.10<sup>-12</sup> at 1-s integration time, limited by the Rb
      clock stability. The demonstrated frequency uncertainty of 6.6.10<sup>-11</sup>
      is mainly limited by the reproducibility of the frequency measurements.

PMID- 28504758
TI  - Pulse picker for synchrotron radiation driven by a surface acoustic wave.
AB  - A functional test for a pulse picker for synchrotron radiation was performed at
      Diamond Light Source. The purpose of a pulse picker is to select which pulse from
      the synchrotron hybrid-mode bunch pattern reaches the experiment. In the present
      work, the Bragg reflection on a Si/B<sub>4</sub>C multilayer was modified using
      surface acoustic wave (SAW) trains. Diffraction on the SAW alters the direction
      of the x rays and it can be used to modulate the intensity of the x rays that
      reach the experimental chamber. Using electronic modulation of the SAW amplitude,
      it is possible to obtain different scattering conditions for different x-ray
      pulses. To isolate the single bunch, the state of the SAW must be changed in the
      short time gap between the pulses. To achieve the necessary time resolution, the
      measurements have been performed in conical diffraction geometry. The achieved
      time resolution was 120 ns.

PMID- 28504759
TI  - Reconfigurable opto-thermal graded-index waveguiding in bulk chalcogenide
      glasses.
AB  - In the absence of suitable deposition processes, the fabrication of graded-index
      chalcogenide waveguides or fibers remains an outstanding challenge. Here, by
      exploiting the strong thermo-optic effect present in chalcogenide glasses, we
      experimentally demonstrate non-permanent optically-induced waveguides in bulk
      As<sub>2</sub>Se<sub>3</sub> rods using a 1.55 MUm wavelength laser. This single
      step process can be used not only to self-trap the writing beam, but also to
      guide another optical beam at a different wavelength in the opto-thermally
      inscribed waveguide channel. These results could pave the way towards harnessing
      nonlinear effects in graded-index chalcogenide guided settings.

PMID- 28504760
TI  - Programmable controlled mode-locked fiber laser using a digital micromirror
      device.
AB  - A digital micromirror device (DMD)-based arbitrary spectrum amplitude shaper is
      incorporated into a large-mode-area photonic crystal fiber laser cavity. The
      shaper acts as an in-cavity programmable filter and provides large tunable
      dispersion from normal to anomalous. As a result, mode-locking is achieved in
      different dispersion regimes with watt-level high output power. By programming
      different filter profiles on the DMD, the laser generates femtosecond pulse with
      a tunable central wavelength and controllable bandwidth. Under conditions of
      suitable cavity dispersion and pump power, design-shaped spectra are directly
      obtained by varying the amplitude transfer function of the filter. The results
      show the versatility of the DMD-based in-cavity filter for flexible control of
      the pulse dynamics in a mode-locked fiber laser.

PMID- 28504761
TI  - High-reflectance magnetron-sputtered scandium-based x-ray multilayer mirrors for
      the water window.
AB  - We present an experimental comparison of several Sc-based short period multilayer
      mirrors including Cr/Sc with B<sub>4</sub>C barrier layers and
      CrN<sub>x</sub>/Sc, and we propose a new material combination that provides high
      reflectance in the water window domain. Multilayer samples with period thickness
      in the range 1.5-1.7 nm have been deposited by magnetron sputtering and
      characterized by x-ray reflectometry with a Cu-Kalpha source and with synchrotron
      radiation near the Sc-L<sub>2,3</sub> edge. Best results are achieved by
      combining the nitridation of Cr layers and the addition of B<sub>4</sub>C barrier
      layers. Near normal incidence reflectance as high as 23% has been measured at
      photon energy of 397 eV. A simulation model of the multilayer structure is
      proposed and it predicts that reflectance higher than 32% is achievable with
      CrN<sub>x</sub>/B<sub>4</sub>C/Sc mirrors.

PMID- 28504762
TI  - Surface enhanced infrared absorption of chemisorbed carbon monoxide using
      plasmonic nanoantennas.
AB  - We report the enhancement of infrared absorption of chemisorbed carbon monoxide
      on platinum in the gap of plasmonic nanoantennas. Our method is based on the self
      assembled formation of platinum nanoislands on nanoscopic dipole antenna arrays
      manufactured via electron beam lithography. We employ systematic variations of
      the plasmonic antenna resonance to precisely couple to the molecular stretch
      vibration of carbon monoxide adsorbed on the platinum nanoislands. Ultimately, we
      reach more than 1500-fold infrared absorption enhancements, allowing for an
      ultrasensitive detection of a monolayer of chemisorbed carbon monoxide. The
      developed procedure can be adapted to other metal adsorbents and molecular
      species and could be utilized for coverage sensing in surface catalytic
      reactions.

PMID- 28504763
TI  - Mirrors with designed spherical aberration for multi-pass cavities.
AB  - We present a novel multi-pass cavity design based on the use of a rotationally
      symmetric end mirror having a specifically designed spherical aberration so that
      its focal length varies inversely as the ray height from the optical axis. We
      provide a detailed discussion of how ray tracing can be done for this system and
      show with numerical simulations that a very rich set of exotic spot patterns can
      be formed on the end mirrors. We further show a specific q-preserving
      configuration where the q-parameters of the input and output beams remain the
      same. Finally, we derive the polar form of the mirror surface profile that gives
      this offset-dependent focal length.

PMID- 28504764
TI  - Enhanced performance in serial-to-parallel data conversion via Raman-assisted
      time lens processing.
AB  - We have demonstrated a new approach to enhance the uniformity of conversion
      efficiency in serial-to-parallel data conversion via time lens processing. In our
      approach, Raman amplification is applied to enhance four-wave mixing in a highly
      nonlinear fiber. By carefully selecting the pump wavelength, the Raman gain
      profile can be exploited to compensate the roll-off in conversion efficiency
      resulted from the varying phase mismatch between the linearly chirped pump and
      the signal. With Raman amplification, improvement of sensitivity up to 6.8 dB has
      been experimentally obtained. The variation of sensitivity across the output
      channels has been reduced from 8.4 to 2.0 dB.

PMID- 28504765
TI  - Thermo-optic characteristic of DNA thin solid film and its application as a
      biocompatible optical fiber temperature sensor.
AB  - We report unique thermo-optical characteristics of DNA-Cetyl tri-methyl ammonium
      (DNA-CTMA) thin solid film with a large negative thermo-optical coefficient of 
      3.4*10<sup>-4</sup>/ degrees C in the temperature range from 20 degrees C to 70
      degrees C without any observable thermal hysteresis. By combining this thermo
      optic DNA film and fiber optic multimode interference (MMI) device, we
      experimentally demonstrated a highly sensitive compact temperature sensor with a
      large spectral shift of 0.15 nm/ degrees C. The fiber optic MMI device was a
      concatenated structure with single-mode fiber (SMF)-coreless silica fiber (CSF)
      single mode fiber (SMF) and the DNA-CTMA film was deposited on the CSF. The
      spectral shifts of the device in experiments were compared with the beam
      propagation method, which showed a good agreement.

PMID- 28504766
TI  - Direct stabilization of optomechanical oscillators.
AB  - We demonstrate a simple and effective technique for stabilizing the oscillation
      amplitude of a radiation pressure driven RF optomechanical oscillator (OMO). By
      controlling the optomechanical gain through a feedback loop that uses the
      oscillation amplitude itself as the feedback parameter, we have been able to
      suppress the amplitude fluctuations and drift. In contrast to more complex
      techniques that only lock the relative wavelength detuning, the proposed
      technique isolates the oscillation amplitude not only from laser wavelength
      variations, but also from laser power variations, ambient temperature variations,
      and coupling gap variations. The amplitude stabilization also improves the
      stability of the oscillation frequency (compared to free-running OMOs).

PMID- 28504767
TI  - Cavity-enhanced thermo-optic bistability and hysteresis in a graphene-on
      Si<sub>3</sub>N<sub>4</sub> ring resonator.
AB  - Cavity-enhanced thermo-optic bistability is studied in a graphene-on
      Si<sub>3</sub>N<sub>4</sub> ring resonator. By engineering the coverage of the
      monolayer graphene on top of the Si<sub>3</sub>N<sub>4</sub> ring resonator, we
      observed a two-fold enhancement in the thermo-optically induced resonance shift
      rate and an 18-fold increase in the effective thermal nonlinear refractive index
      compared with the devices without graphene. The thermo-optic hysteresis loop was
      also characterized in this hybrid structure, where the experimental results agree
      well with the theoretical calculations. This Letter paves the way for graphene-on
      Si<sub>3</sub>N<sub>4</sub>-based high-speed photodetectors, modulators, and
      devices for on-chip nonlinear optical applications.

PMID- 28504768
TI  - Spatial integration by a dielectric slab and its planar graphene-based
      counterpart.
AB  - In this contribution a new approach to perform spatial integration is presented
      using a dielectric slab. Our approach is indeed based on the fact that the
      transmission coefficient of a simple dielectric slab at its mode excitation angle
      matches the Fourier-Green's function of first-order integration. Inspired by the
      mentioned dielectric-based integrator, we further demonstrate its graphene-based
      counterpart. The latter is not only reconfigurable but also highly miniaturized
      in contrast to the previously reported designs [Opt. Commun.338, 457
      (2015)OPCOB80030-401810.1016/j.optcom.2014.11.007]. Such integrators have the
      potential to be used in ultrafast analog computation and signal processing.

PMID- 28504769
TI  - Semitransparent and flexible perovskite solar cell with high visible
      transmittance based on ultrathin metallic electrodes.
AB  - We have fabricated semitransparent and flexible indium-free perovskite solar
      cells (PeSCs) with high visible transmittance employing two kinds of composite
      ultrathin metallic electrodes, MoO<sub>3</sub>/Au and
      MoO<sub>3</sub>/Au/Ag/MoO<sub>3</sub>/Alq<sub>3</sub>, as the bottom and top
      electrodes, respectively. These electrodes show superb electrical conductivity,
      excellent mechanical robustness, and high optical transparency which are quite
      suitable for semitransparent and flexible PeSCs. An overall power conversion
      efficiency (PCE) of 6.96% and an average visible transmittance of 18.16% in the
      wavelength range of 380-790 nm were achieved. Furthermore, the devices maintained
      71% of their initial PCE after 1000 bending cycles with a bending radius of 4 mm.

PMID- 28504770
TI  - Umov effect in single-scattering dust particles: effect of irregular shape.
AB  - The Umov effect manifests itself as an inverse correlation between the light
      scattering maximum of positive polarization P<sub>max</sub> and the geometric
      albedo A of the target. In logarithmic scales, P<sub>max</sub> is linearly
      dependent on A. This effect has been long known in the optics of particulate
      surfaces and, recently, it was extended for the case of single-scattering dust
      particles whose size is comparable to the wavelength of the incident light. In
      this work, we investigate the effect of irregular shape on the Umov effect in
      single-scattering particles. Using the discrete dipole approximation (DDA), we
      model light scattering by two different types of irregularly shaped particles.
      Despite significant differences in their morphology, both types of particles
      reveal remarkably similar diagrams of log(P<sub>max</sub>) versus log(A).
      Moreover, in a power-law size distribution r<sup>-n</sup> with n=2.5-3.0, the
      Umov diagrams in both types of particles nearly coincide. This suggests little
      dependence on the shape of target particles in the retrieval of their reflectance
      using the Umov effect.

PMID- 28504771
TI  - Laguerre-Gaussian modal q-plates.
AB  - We propose space-variant uniaxial flat optical elements designed to generate pure
      Laguerre-Gaussian modes with arbitrary azimuthal and radial indices l and p from
      an incident Gaussian beam. This is done via the combined use of the dynamic and
      the geometric phases. Optimal design protocol for the mode conversion efficiency
      is derived, and the corresponding characteristics are given for -6<=l<=6 and
      0<=p<=5. The obtained "modal q-plates" may find many applications whenever the
      radial degree of freedom of a light field is at play.

PMID- 28504772
TI  - Patient flow in Acute Medical Units. A design approach to flow improvement.

PMID- 28504773
TI  - Challenges and 'obstacles': reframing our perspective on the transition into
      adulthood for young people with life-limiting and life-threatening conditions.

PMID- 28504774
TI  - Yoshinori Ohsumi's Nobel Prize for mechanisms of autophagy: from basic yeast
      biology to therapeutic potential.
AB  - On 3 October 2016, Japanese cell biologist Yoshinori Ohsumi was awarded the Nobel
      Prize in Physiology or Medicine 'for his discoveries of mechanisms for
      autophagy'; autophagy being an intracellular degradation pathway that helps
      maintain cytoplasmic homeostasis. This commentary discusses Ohsumi's Nobel prize
      winning work in context, before explaining the clinical relevance of autophagy.

PMID- 28504775
TI  - Efficacy of epidural blood patches for spontaneous low-pressure headaches: a case
      series.
AB  - Patients with a spontaneous cerebrospinal fluid leak, normally at a spinal level,
      typically present with low-pressure headache. In refractory cases, an epidural
      blood patch may be attempted. We aimed to assess the efficacy of lumbar epidural
      blood patching in spontaneous, low-pressure headaches. Methods We retrospectively
      analysed notes of patients who had an epidural blood patch performed for
      spontaneous low-pressure headaches in a single centre. Information regarding
      demographics, radiology and clinic follow-up was extracted from an electronic
      patient record system. Questionnaires regarding outcome were sent to patients a
      minimum of 6 months post-procedure. All patients received an epidural blood patch
      in the lumbar region irrespective of the site of cerebrospinal fluid leak.
      Results Sixteen patients who underwent lumbar epidural blood patching were
      analysed (11 female; mean age 43 years). The site of cerebrospinal fluid leak was
      evident in only 3/16 patients. Thirteen patients attended clinic follow-up; three
      reported complete headache resolution, four reported improvement in intensity or
      frequency and six described no change. Five of eight questionnaire respondents
      reported reduction in pain, and in these responders, mean headache severity
      improved from 9/10 to 3/10. Five of eight patients returning follow-up
      questionnaires reported sustained improvement in headache symptoms. Conclusion
      Epidural blood patch procedures can provide sustained improvement in headache
      symptoms in selected patients with spontaneous intracranial hypotension, but an
      untargeted approach has a lower success rate than reported in other case series.

PMID- 28504776
TI  - Insulin-mediated hypoglycaemia secondary to recurrent clear cell renal carcinoma.
AB  - Renal cell carcinoma has previously been associated with hypoglycaemia in the
      setting of non-islet cell tumours, caused by a paraneoplastic phenomenon relating
      to the production of insulin-like growth factor type II. We present a case of
      recurrent clear cell renal cell carcinoma, leading to an insulin-mediated
      paraneoplastic phenomenon causing severe recurrent hypoglycaemia. Hypoglycaemina
      was managed successfully using diazoxide therapy, in conjunction with pazopanib
      and radiotherapy to reduce tumour burden.

PMID- 28504777
TI  - Dengue fever with compartment syndrome of the right arm.
AB  - A 44-year-old woman was admitted to our hospital with dengue fever. She developed
      a haematoma in the right arm at the site of a previous arterial line insertion.
      Due to coexisting thrombocytopenia, the bleeding was severe enough to cause
      compartment syndrome. An emergency fasciotomy was performed and her limb
      salvaged. The case illustrates one important potential complication of this
      common infectious disease.

PMID- 28504778
TI  - Chorea in the older adult: a full blooded answer.
AB  - Chorea is a severe, distressing, movement disorder characterised by excessive,
      purposeless movements of the limbs, head and orofacial muscles in a generalised
      and irregularly-timed fashion. In young patients, neurodegenerative (Huntington's
      disease) and metabolic (Wilson's disease) aetiologies are most common. In the
      older population, the differential widens to include genetic, structural,
      metabolic and pharmacological causes. We present a case of an older man who
      developed progressive choreoathetosis secondary to polycythaemia vera which
      resolved with serial venesections. The treatment of his underlying condition is
      discussed.

PMID- 28504779
TI  - Unilateral retinal racemose haemangioma with cataract.

PMID- 28504780
TI  - Is tenofovir the answer to further preventing mother-to-child transmission of
      hepatitis B?

PMID- 28504781
TI  - Expanding the evidence base in the pharmacological management of vasovagal
      syncope - the next POST.

PMID- 28504782
TI  - Fatal Accident Inquiries: raising awareness of their role in relation to the
      medical profession in Scotland.

PMID- 28504783
TI  - Reading books and reading patients: can Book Clubs help both?

PMID- 28504784
TI  - Current clinical controversies in the management of sepsis.
AB  - Sepsis remains a challenging clinical problem requiring prompt diagnosis and
      optimal clinical management if the continuing high mortality is to be contained.
      In this brief review I consider four specific questions that are the subject of
      ongoing controversy. First, whether the new 'Sepsis-3' definitions will be
      helpful, in particular in improving diagnosis, or whether the rapid move towards
      precision medicine will make the definition redundant. Second, should we
      routinely use combinations of antibiotics for the empiric treatment of sepsis.
      Third, whether there is any clinical benefit in continuous rather than bolus
      administration of beta-lactam antibiotics. Finally, whether there is good
      evidence that biomarkers such as procalcitonin can help reduce the duration of
      antibiotic therapy.

PMID- 28504785
TI  - Addressing noncommunicable diseases in primary care: the case of type 2 diabetes.
AB  - The rapid growth of noncommunicable diseases represents a formidable global
      health challenge. Here we use type 2 diabetes as a case study to illustrate the
      rise of noncommunicable diseases and call attention to the important role of
      primary care systems in addressing these diseases in low- and middle-income
      countries. Comprehensive screening for diabetes should be implemented through
      primary care systems to increase early detection of prediabetes and undiagnosed
      diabetes - a first step to diabetes prevention and management. In addition,
      primary care systems should strengthen and expand capacity to link patients to
      appropriate interventions based on their diabetes status and provide care
      coordination (e.g. leveraging task-shifting and technology), and integrate clinic
      and community resources for diabetes prevention and control. Additional
      strategies should include continuous quality improvement, health systems
      strengthening, workforce development, and affordable and sustainable financing.
      Together, these actions could elevate the role of primary care in addressing
      diabetes in low- and middle-income countries and help advance global progress
      towards reducing diabetes complications, and also preventing or delaying diabetes
      among those at risk.

PMID- 28504786
TI  - The way we die now: a personal reflection.

PMID- 28504787
TI  - Medical humanities: some uses and problems.
AB  - The arts and humanities were allowed into the British medical curriculum in 1993
      when the General Medical Council re-structured it in a paper entitled 'Tomorrow's
      Doctors'. Since then many medical schools have developed humanities modules and
      the broad term 'medical humanities' refers to these. They can contribute to
      medical education in at least three ways: as a supplement to what is already in
      the curriculum, especially for ethics and communication; as an outside critique
      of medical practice; and to personal and professional development. Nevertheless,
      there are practical problems concerning appropriate teachers and methods of
      assessment. Moreover, the dominant interest is now academic research rather than
      education.

PMID- 28504788
TI  - Are medical eponyms really dying out? A study of their usage in the historical
      biomedical literature.
AB  - Eponyms are a prominent feature of medical language. Many feel they have had
      their time and serve only to complicate medical education and conversation.
      Others argue that eponyms can make unmemorable concepts memorable, can concisely
      label complex concepts, and promote a valuable interest in medical history. It is
      frequently assumed that medical eponyms are marching towards extinction. However,
      this hypothesis has not been adequately tested. The fate of 8,636 eponyms from
      contemporary and historical registers is presented here. The annual usage of each
      eponym in PubMed indexed articles since 1900 is analysed with metrics of eponym
      prevalence, coinage and extinction. The fate of eponyms named for those
      implicated in Nazi war crimes is also measured. The analysis shows that more
      publications used an eponym in their title in 2014 than ever before. However, the
      proportion using an eponym title has fallen from a peak of 3% in 1991 to 2%
      today, while annual extinction of eponyms overtook coinage in the 1980s. This
      suggests that, while not in dramatic decline, they are perhaps losing market
      share to more scientific descriptions. There is no ambiguity in the fate of
      eponyms related to Nazi war crimes which have almost entirely fallen out of use
      in the last decade.

PMID- 28504789
TI  - Personalised approach to anticoagulation

PMID- 28504790
TI  - Fast tuning of covalent triazine frameworks for photocatalytic hydrogen
      evolution.
AB  - A fast and facile route for the optimization of covalent triazine frameworks
      (CTFs) for photocatalytic hydrogen production is presented. Within 10 minutes a
      CTF with low photocatalytic activity can be converted into a highly active
      photocatalyst. Optimized CTF catalysts show an average hydrogen evolution rate of
      1072 MUmol h-1 g-1 under visible light (>420 nm).

PMID- 28504791
TI  - Mapping gas phase dipeptide motions in the far-infrared and terahertz domain.
AB  - Vibrational signatures of Ac-Phe-AA-NH2 dipeptides are recorded and analysed in
      the far IR/THz spectral domain (100-800 cm-1, 3-24 THz), with the 'AA' amino acid
      chosen within the series 'AA' = Gly, Ala, Pro, Cys, Ser, Val. Phe stands for
      phenylalanine. IR-UV ion dip experiments are conducted on the free electron laser
      FELIX and combined with DFT-based molecular dynamics simulations for the
      calculation of the dynamical anharmonic vibrational spectra. The excellent
      agreements between the experimental and theoretical spectra of the Ac-Phe-AA-NH2
      series allow us to make detailed and unambiguous mapping of the vibrational
      motions into three main domains: 700-800 cm-1 for C-H waggings, 400-700 cm-1 for
      N-H waggings, with a one-to-one signature per amide N-H backbone group, 0-400 cm
      1 for delocalized and large amplitude collective motions over the dipeptide
      backbone, with backbone torsional motions arising <100 cm-1.

PMID- 28504792
TI  - Cu(iii)triarylcorroles with asymmetric push-pull meso-substitutions: tunable
      molecular electrochemically catalyzed hydrogen evolution.
AB  - The synthesis of four low symmetry A2B type Cu(iii)triarylcorroles with meso-aryl
      substituents that provide electron donating (push) and withdrawing (pull)
      properties is reported, along with their structural characterization by NMR
      spectroscopy and X-ray crystallography. An analysis of the structure-property
      relationships in the optical and redox properties has been carried out by
      comparing their optical spectroscopy, electrochemistry, and
      spectroelectrochemistry to trends predicted in DFT and TD-DFT calculations. The
      results demonstrate that A2B type Cu(iii)triarylcorroles are highly efficient
      catalysts for electrocatalyzed hydrogen evolution reactions (HERs) and that their
      reactivity can be modulated by changing the nature of the B-position meso
      substituent.

PMID- 28504794
TI  - Reactive oligo(dimethylsiloxane) mesogens and their nanostructured thin films.
AB  - Oligo(dimethylsiloxane)-based reactive mesogens were prepared and shown to form
      room-temperature smectic phases which were 'frozen-in' by photopolymerization.
      Homeotropically aligned, nanostructured thin films were obtained by spincoating,
      and micropatterning was demonstrated. These hybrid reactive mesogens are suitable
      for the preparation of aligned nanostructured polymer thin films with potential
      applications ranging from stimuli responsive coatings to nanoporous membranes.

PMID- 28504793
TI  - Generating single metalloprotein crystals in well-defined redox states:
      electrochemical control combined with infrared imaging of a NiFe hydrogenase
      crystal.
AB  - We describe an approach to generating and verifying well-defined redox states in
      metalloprotein single crystals by combining electrochemical control with
      synchrotron infrared microspectroscopic imaging. For NiFe hydrogenase 1 from
      Escherichia coli we demonstrate fully reversible and uniform electrochemical
      reduction from the oxidised inactive to the fully reduced state, and temporally
      resolve steps during this reduction.

PMID- 28504796
TI  - Formation of high-molecular weight polyaminoborane by Fe hydride catalysed
      dehydrocoupling of methylamine borane.
AB  - The complex [(PNHP)Fe(H)(CO)(HBH3)] (PNHP = HN(CH2CH2Pi-Pr2)2) serves as a
      catalyst precursor for the selective dehydrocoupling of methylamine borane at
      room temperature, tentatively via an off-metal polymerisation pathway.

PMID- 28504797
TI  - Advancing polyethylene properties by incorporating NO2 moiety in 1,2
      bis(arylimino)acenaphthylnickel precatalysts: synthesis, characterization and
      ethylene polymerization.
AB  - A new family of nickel halides (bromides Ni1-Ni5 and chlorides Ni6-Ni10) ligated
      by 1-(2,6-dibenzhydryl-4-nitrophenylimino)-2-(arylimino)acenaphthylene (Aryl =
      2,6-Me2C6H3L1, 2,6-Et2C6H3L2, 2,6-iPr2C6H3L3, 2,4,6-Me3C6H2L4, and 2,6-Et2-4
      MeC6H2L5) have been prepared and well characterized, and the scope of their
      catalytic properties toward the polymerization of ethylene has been investigated.
      Upon activation with either Et2AlCl or EASC, the nickel bromide complexes
      displayed better activities than their nickel chloride counterparts and produced
      higher-molecular-weight polyethylene in the range of 106 g mol-1 with a very
      narrow range of molecular weight distributions. In comparison with reference
      precatalysts with non-nitro substituents (CH3, F or Cl), the title complexes
      experienced a modest negative effect on catalytic activity upon replacement with
      a NO2 moiety (activity up to 4.61 * 106 g PE (mol Ni)-1 h-1 at 20  degrees C).
      Conversely, the NO2 moiety exerted a positive effect to increase the molecular
      weight of the resulting polyethylene, and Ni4/Et2AlCl gave polyethylene with a
      maximum molecular weight of as high as 32.8 * 105 g mol-1, which is not only the
      highest among the title complexes but also higher than any literature values
      reported with 1,2-diiminoacenaphthylnickel halides.

PMID- 28504795
TI  - Label-free detection of DNA hybridization with a compact LSPR-based fiber-optic
      sensor.
AB  - A miniaturized, robust, localized surface plasmon resonance (LSPR)-coupled fiber
      optic (FO) nanoprobe providing an integrated and portable solution for detection
      of DNA hybridization and measurement of DNA concentrations has been demonstrated.
      The FO nanoprobe was created by constructing arrays of metallic nanostructures on
      the end facets of optical fibers utilizing nanofabrication technologies,
      including electron beam lithography and lift-off processes. The LSPR-FO nanoprobe
      device offers real-time, label-free, and low-sample-volume quantification of
      single-strand DNA in water with high sensitivity and selectivity, achieving a
      limit of detection around 10 fM. These results demonstrate the feasibility of the
      LSPR-FO nanoprobe device as a compact and low-cost biosensor for detection of
      short-strand DNA.

PMID- 28504798
TI  - A vacuum ultraviolet photoionization study on high-temperature decomposition of
      JP-10 (exo-tetrahydrodicyclopentadiene).
AB  - Two sets of experiments were performed to unravel the high-temperature pyrolysis
      of tricyclo[5.2.1.02,6] decane (JP-10) exploiting high-temperature reactors over
      a temperature range of 1100 K to 1600 K, Advanced Light Source (ALS), and 927 K
      to 1083 K, National Synchrotron Radiation Laboratory (NSRL), with residence times
      of a few tens of microseconds (ALS) to typically 144 ms (NSRL). The products were
      identified in situ in supersonic molecular beams via single photon vacuum
      ultraviolet (VUV) photoionization coupled with mass spectroscopic detection in a
      reflectron time-of-flight mass spectrometer (ReTOF). These studies were designed
      to probe the initial (ALS) and also higher order reaction products (NSRL) formed
      in the decomposition of JP-10 - including radicals and thermally labile closed
      shell species. Altogether 43 products were detected and quantified including C1
      C4 alkenes, dienes, C3-C4 cumulenes, alkynes, eneynes, diynes, cycloalkenes,
      cyclo-dienes, aromatic molecules, and most importantly, radicals such as ethyl,
      allyl, and methyl produced at shorter residence times. At longer residence times,
      the predominant fragments were molecular hydrogen (H2), ethylene (C2H4), propene
      (C3H6), cyclopentadiene (C5H6), cyclopentene (C5H8), fulvene (C6H6), and benzene
      (C6H6). Accompanied by electronic structure calculations, the initial JP-10
      decomposition via C-H bond cleavages resulting in the formation of the initial
      six C10H15 radicals was found to explain the formation of all products detected
      in both sets of experiments. These radicals are not stable under the experimental
      conditions and further decompose via C-C bond beta-scission processes. These
      pathways result in ring opening in the initial tricyclic carbon skeletons of JP
      10. Intermediates accessed after the first beta-scission can further isomerize or
      dissociate. Complex PAH products in the NRLS experiment (naphthalene,
      acenaphthylene, biphenyl) are likely formed via molecular growth reactions at
      elevated residence times.

PMID- 28504800
TI  - Experimental and computational study of the magnetic properties of ZrMn2
      xCoxGe4O12.
AB  - Polycrystalline samples in the solid solution ZrMn2-xCoxGe4O12 (x = 0.0, 0.5,
      1.0, 1.5 and 2.0) have been prepared using the ceramic method and characterised
      by a combination of magnetometry, X-ray diffraction and neutron diffraction. They
      all adopt the space group P4/nbm with a ~ 9.60, c ~ 4.82 A and show long-range
      magnetic order with transition temperatures, TC, in the range 2 <= TC/K <= 10.
      The underlying magnetic structure is the same in each case but the ordered spins
      lie along [001] when x = 0.0 and in the (001) plane for all other compositions.
      In all cases the magnetically-ordered phase is a weak ferromagnet although the
      magnitude of the spontaneous magnetisation and the strength of the coercive field
      are composition-dependent. The magnetic structure can be rationalized by
      considering the strengths of the interactions along the distinct M-O-Ge-O-M
      superexchange pathways in the crystal and the observed magnetic structure is
      entirely consistent with the predictions of ab initio calculations.

PMID- 28504801
TI  - A Pt(0) complex with cyclic (alkyl)(amino)silylene and 1,3-divinyl-1,1,3,3
      tetramethyldisiloxane ligands: synthesis, molecular structure, and catalytic
      hydrosilylation activity.
AB  - A platinum(0) complex bearing a cyclic (alkyl)(amino)silylene and a 1,3-divinyl
      1,1,3,3-tetramethyldisiloxane (DVTMS) was synthesized and isolated in the form of
      colorless crystals. The single-crystal X-ray diffraction analysis of this complex
      in combination with theoretical calculations indicated that the Pt->Si pi-back
      donation in this complex is weaker than that in the corresponding cyclic
      dialkylsilylene-ligated Pt complex. The performance of this complex in the
      catalytic hydrosilylation of (Me3SiO)2MeSi-H with various terminal alkenes that
      contain functional groups was comparable to that of the corresponding cyclic
      dialkylsilylene/DVTMS Pt(0) complex.

PMID- 28504802
TI  - A temperature-resolved assembly of a series of the largest scandium-containing
      polyoxotungstates.
AB  - We report a temperature-resolved assembly of a series of novel nanoscale
      hexameric Sc-containing polyoxometalates of {Sb6Sc11W60}, {Sb8Sc7W60}, and
      {Sb8Sc6W60}. These compounds include the largest Sc-containing polyoxotungstates
      and contain the largest number of Sc3+ ions of any polyoxotungstates reported to
      date.

PMID- 28504805
TI  - Monitoring of nanoparticle reactivity in solution: interaction of l-lysine and Ru
      nanoparticles probed by chemical shift perturbation parallels regioselective H/D
      exchange.
AB  - Thanks to new water-soluble Ru nanoparticles (NPs) stabilized by sulfonated NHC
      ligands, we demonstrate that it is possible to monitor the catalyst/substrate
      interaction using NMR chemical shift perturbations (CSPs), under conditions that
      closely resemble those applied during the enantiospecific C-H deuteration of l
      lysine. Correlating the pH dependence of the interaction of l-lysine with the
      surface of the RuNPs and its subsequent deuteration, our study underscores the
      importance of oriented binding to the surface as a critical factor for H/D
      exchange.

PMID- 28504807
TI  - Occupational class and working beyond the retirement age: a cohort study.
AB  - Objectives The aim of this study was to examine occupational class differences in
      working more than six months beyond the mandatory retirement age and factors that
      may contribute to these differences. Methods The study comprised a prospective
      cohort study of a total of 5331 Finnish municipal employees (73% women) who were
      not on work disability pension and reached the age eligible for old-age pension
      in 2005-2011. Occupational class included four categories: managers and
      professionals, lower grade non-manual, skilled manual, and elementary
      occupations. Survey responses while at work were linked to national health and
      pension registers. Results A total of 921 participants (17.3%) worked beyond the
      pensionable age. Compared with elementary workers, skilled manual workers had a
      similar probability [gender-adjusted risk ratio (RR) 0.95, 95% confidence
      interval (95% CI) 0.72-1.23] while lower grade non-manual workers had a 2.03-fold
      (95% CI 1.59-2.58), and managers and professionals had a 1.79-fold (95% CI 1.41
      2.27) probability of working beyond the pensionable age. Adjustment for physical
      workload (32.0% in lower non-manual, 36.7% in managers and professionals), work
      time control (20.4% and 11.4%) and perceived work ability (16.5% and 29.1%)
      contributed to the largest attenuation for these associations. Analyses using a
      counterfactual approach suggested greater mediated effects for physical workload
      and work time control than those observed in traditional mediation analyses.
      Conclusions Employees with higher occupational classes are two times more likely
      to continue working beyond the retirement age compared to those with lower
      occupational classes. A large proportion of these differences were explained by
      having physically light job, better work time control, and better self-rated work
      ability among employees with high occupational class.

PMID- 28504808
TI  - Outcome of Reverse Shoulder Arthroplasty for Patients With Parkinson's Disease: A
      Matched Cohort Study.
AB  - Parkinson's disease (PD) is a progressive neurologic disorder that affects the
      musculoskeletal system. Currently, the use of reverse shoulder arthroplasty (RSA)
      for patients with PD has not been adequately studied. The authors sought to
      determine if RSA provided similar functional outcomes for patients with PD
      compared with a matched cohort of patients without PD. Between 2004 and 2011, 10
      patients with PD (4 men, 6 women) underwent RSA. Patients with PD were matched to
      patients without PD at a 1:4 ratio based on age (average, 76 years; range, 63-85
      years), sex (16 men, 24 women), preoperative diagnosis, and length of follow-up
      (average, 43 months; range, 24-128 months). Outcome measures included range of
      motion, visual analog scale (VAS) score, Simple Shoulder Test (SST) score,
      American Shoulder and Elbow Society (ASES) score, and complication rates.
      Patients with PD had improvements in SST scores, ASES total scores, and forward
      flexion; however, they did not show statistically significant improvements in VAS
      scores, ASES function scores, or other range of motion parameters. There was a
      significant difference in postoperative functional outcome scores, SST scores,
      and internal/external rotation between the 2 groups, but no difference in
      postoperative pain scores, ASES total scores, forward flexion, or abduction.
      Complications occurred in 4 of 10 patients with PD and 6 of 40 patients without
      PD. Compared with the matched cohort, patients with PD achieved similar reduction
      of pain but inferior clinical function following RSA. Improvement in range of
      motion was less predictable and complication rates were significantly higher in
      patients with PD. [Orthopedics. 2017; 40(4):e675-e680.].

PMID- 28504809
TI  - Effect of Lymphedema Treatment for Management of Acute Pilon Fractures.
AB  - Pilon fractures are high-energy injuries that often result in considerable edema
      and compromise of the soft tissue envelope of the ankle. These injuries are
      typically staged with an external fixator until the soft tissue is amenable for
      definitive fixation. This study was conducted to determine the effects of
      lymphedema treatment for the management of pilon fractures. Patients who
      underwent open reduction and internal fixation of pilon fractures between 2007
      and 2014 at the authors' level II trauma center were identified by Current
      Procedural Terminology codes indicative of placement of an external fixator
      (20690) and open reduction and internal fixation of a pilon fracture (27826,
      27827, or 27828). The primary efficacy endpoint to determine negative outcomes
      was 90 days after definitive fixation. Eighty-two patients with 84 pilon
      fractures met inclusion criteria. Forty-eight ankles (57%) received lymphedema
      treatment. There were no significant differences in population demographics
      between the control and treatment groups. Median times to internal fixation in
      the control and treatment groups were 20 days (inter-quartile range, 15.5-30
      days) and 11 days (interquartile range, 6-18 days), respectively. This difference
      was statistically significant (P=.001). Additionally, there was no significant
      difference in the overall incidence of wound complications between the control
      and treatment groups (P=.246). Compression wrapping for posttraumatic edema was
      effective in reducing the time needed for soft tissues to be appropriate for
      definitive surgical fixation of pilon fractures without increasing the risk of
      wound complications. These promising results warrant future study. [Orthopedics.
      2017; 40(4):e668-e674.].

PMID- 28504810
TI  - Using a Structured Checklist to Improve the Orthopedic Ward Round: A Prospective
      Cohort Study.
AB  - Comprehensive and timely documentation on orthopedic ward rounds continues to be
      problematic, leading to delayed or inappropriate patient care and
      miscommunication between health care providers. The authors introduced a simple
      checklist to improve the documentation on orthopedic ward rounds in their
      institution. A prospective cohort study was performed. Standard care was provided
      for cohort A. During a 2-week period, the documentation of patient care by
      physicians following a ward round was assessed in terms of venous thromboembolism
      prophylaxis, fasting status, wound or dressing plan, weight-bearing status, and
      important surgical details. The physicians were blinded to this initial review.
      For cohort B, a structured ward round checklist was introduced during a 2-week
      period. A total of 132 patient encounters were recorded in cohort A. Important
      issues that were rarely discussed included vital signs (11.4%), venous
      thromboembolism prophylaxis (9.8%), and bowel status (3.8%). Issues that were
      poorly documented included fasting status (9.1%), wound or dressing plan (6.8%),
      and weight-bearing status (11.4%). After introduction of the checklist, daily
      documentation of surgical details improved from 38.6% to 85.3% of patient
      encounters. Fasting status documentation improved from 9.1% to 70.6% of patient
      encounters. Venous thromboembolism prophylaxis discussion increased from 9.8% to
      45.6% of the time, while its documentation improved from 6.8% to 92.6%.
      Documentation of weight-bearing status improved from 11.4% to 83.8% (all
      P<.0001). The use of a structured checklist during orthopedic ward rounds led to
      significant improvement in both the consideration and the documentation of key
      aspects of surgical care. [Orthopedics. 2017; 40(4):e663-e667.].

PMID- 28504811
TI  - Percutaneous Screw Fixation for Scaphoid Fractures.
AB  - Treatment of nondisplaced scaphoid waist fractures has evolved from conventional
      cast immobilization to percutaneous screw insertion. This study assessed clinical
      and radiologic outcomes of volar percutaneous screw fixation for 15 type B2
      scaphoid fractures (according to the Herbert and Fisher classification). All
      patients were followed for an average of 33 months (range, 6-50 months). All
      fractures achieved radiographic union at an average of 57 days (range, 35-70
      days), requiring no additional procedures. None of the patients showed
      radiographic signs of osteoarthritis, osteonecrosis of the scaphoid, or hardware
      related complications. For scaphoid waist fractures without collapse,
      percutaneous screw fixation provided satisfactory results with a high rate of
      union, early return of function, and minimal complications. [Orthopedics. 2017;
      40(4):e729-e734.].

PMID- 28504812
TI  - Overexpression of the YAP1 oncogene in clear cell renal cell carcinoma is
      associated with poor outcome.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70
      80%). Yes-associated protein 1 (YAP1) protein is a nuclear effector of the Hippo
      pathway and acts as a transcriptional co-activator of genes involved in the
      processes of growth and development of tissues. Hippo signaling, with its key
      kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant
      role in the negative regulation of the amount and activity of YAP1 protein.
      Components of the Hippo pathway and YAP1 levels are frequently dysregulated in a
      variety of tumors, suggestive of their possible involvement in carcinogenesis.
      Our aim was to evaluate gene and protein expression profiles of YAP1, MST2 and
      LATS1 and the methylation status of MST2 and LATS1 promoters in ccRCC. mRNA
      levels of MST2, LATS1 and YAP1 genes were assessed in the tumor and matched
      normal kidney tissues of 86 patients, and in 12 samples of local metastases by
      quantitative PCR (qPCR). Proteins were semi-quantified in 58 patient samples by
      western blotting. Hypermethylation of LATS1 and MST2 promoters was measured by
      methylation-specific high-resolution-melting qPCR. We found that LATS1 promoter
      hypermethylation, decreased LATS1 mRNA/protein and increased YAP1 mRNA/protein
      levels in tumor samples were associated with higher TNM and Fuhrman's stages and
      patient survival. Higher YAP1 mRNA levels were associated with poor outcome
      (HR=4.03, p=0.036). No changes in MST2 (promoter/mRNA/protein) were found. We
      propose that deregulation of LATS1 and YAP1 expression is associated with ccRCC
      progression and poor patient survival. Measurement of YAP1 mRNA levels in paired
      tumor-normal kidney tissue samples may serve as a new prognostic factor in ccRCC.

PMID- 28504813
TI  - Improved xenograft efficiency of esophageal adenocarcinoma cell lines through in
      vivo selection.
AB  - The present study aimed to investigate the orthotopic growth potential of two
      generally available esophageal adenocarcinoma cell lines, OE33 and OACM5 1.C, and
      a third in vivo selected subpopulation, OACM5 1.C SC1. One group of mice was
      subcutaneously injected in the hind legs. Tumor growth was measured with
      calipers. Another group was injected orthotopically in the distal esophageal wall
      through median laparotomy. Tumor development was evaluated macroscopically and
      confirmed microscopically. A subset of mice was evaluated with magnetic resonance
      imaging (MRI) to follow tumor progression. Additionally, functional cell line
      characteristics were evaluated in vitro (clonogenic, collagen invasion and sphere
      formation assays, and protein analysis of cell-cell adhesion and cytoskeletal
      proteins) to better understand xenograft behavior. OE33 cells were shown to be
      epithelial-like, whereas OACM5 1.C and OACM5 1.C SC1 were more mesenchymal-like.
      The three cell lines were non-invasive into native type I collagen gels. In vivo,
      OE33 cells led to 63.6 and 100% tumor nodules after orthotopic (n=12) and
      subcutaneous (n=8) injection, respectively. Adversely, OACM5 1.C cells did not
      lead to tumor formation after orthotopic injection (n=6) and only 50% of
      subcutaneous injections led to tumor nodules (n=8). However, the newly
      established cell line OACM5 1.C SC1 resulted in 33% tumor formation when
      orthotopically injected (n=6) and in 100% tumors when injected subcutaneously
      (n=8). The higher xenograft rate of OACM5 1.C SC1 (P<0.05) corresponded with a
      higher clonogenic potential compared to its parental cell line (P<0.0001). All
      models showed local tumor growth without metastasis formation. In conclusion,
      OACM5 1.C has a poor tumor take rate at an orthotopic and ectopic site. A
      subpopulation obtained through in vivo selection, OACM5 1.C SC1, gives a
      significant higher take rate, ectopically. Furthermore, OE33 establishes
      orthotopic (and subcutaneous) xenografts in mice. These models can be of interest
      for future studies, and their slow growth rates are a challenge for therapeutic
      intervention.

PMID- 28504814
TI  - MicroRNA-212 inhibits the metastasis of nasopharyngeal carcinoma by targeting
      SOX4.
AB  - MicroRNAs are important factors in the pathogenic processes of human types of
      cancers including nasopharyngeal carcinoma (NPC). In the present study, we
      confirmed that the microRNA-212 expression level was significantly decreased both
      in NPC tissues and NPC cell lines. Decreased expression of miR-212 was associated
      with advanced tumor-node-metastasis (TNM) stage and metastasis of NPC. Patients
      with a lower level of miR-212 had significantly decreased rates of overall and
      disease-free survival. Functional experiments showed that forced expression of
      miR-212 inhibited the migration and invasion of NPC cells while inhibition of miR
      212 increased the migration and invasion of NPC cells. Furthermore, the results
      of luciferase assay, qRT-PCR and western blotting showed that SOX4 was the direct
      downstream target of miR-212 in NPC cells. In addition, we further confirmed that
      miR-212 exerted its inhibitory influence on the migration and invasion of NPC
      cells by targeting SOX4.

PMID- 28504815
TI  - The Arago Laboratory of Banyuls and some of its Academicians.
AB  - Since its founding in 1881 by Henri de Lacaze-Duthiers (1821-1901), the Arago
      Laboratory of Banyuls has been one of the three marine stations of the University
      Pierre and Marie Curie-Paris 6. It is located in Banyuls (Banyuls-sur-Mer) in
      Northern Catalonia. The center hosts researchers and students from all over the
      world. Some became famous, including four Nobel Prize winners: Andre Lwoff
      (1965), Pierre-Gilles de Gennes (1991), Albert Fert (2007) and Jules Hoffmann
      (2011). This article focuses on five scientists closely related to the center.
      The first three are Henri de Lacaze-Duthiers (1821-1901), the founder; Edouard
      Chatton (1883-1947), eminent director of the center; and Andre Lwoff (1902-1994),
      who before being known for his work in bacterial genetics and virology was an
      outstanding protozoologist under the direction of Chatton. Lynn Margulis (1938
      2011), a great friend of the Arago Laboratory and personal friend of the author,
      is also remembered. Finally, there is a mention of Walter J. Gehring (1939-2014),
      professor at the University of Basel, Switzerland. [Int Microbiol 19(4): 183-190
      (2016)].

PMID- 28504816
TI  - Virulence factors and antimicrobial resistance in environmental strains of Vibrio
      alginolyticus.
AB  - Vibrio alginolyticus has acquired increasing importance because this
      microorganism may be pathogenic to aquatic animals and humans. It has been
      reported that some V. alginolyticus strains carry virulence genes derived from
      pathogenic V. cholerae and V. parahaemolyticus strains. In this work V.
      alginolyticus was isolated from oyster samples acquired from a food-market in
      Mexico City. Thirty isolates were identified as V. alginolitycus. Strains showed
      beta-haemolysis and proteolytic activity and produced a capsule. Strains
      displayed swimming and swarming motility and 93.3% of them produced siderophores.
      Several genes encoding virulence factors were detected using PCR amplification.
      These included proA, wza, vopD, vopB, hcp, vasH and vgrG genes, which were
      present in all strains. Other genes had a variable representation: tdh (86.6%),
      lafA (96.6%), pvsA (62%) and pvuA (16%). The trh gene could not be amplified from
      any of the strains. The antimicrobial resistance profile revealed that more than
      90% of the strains were resistant to beta-lactams antibiotics, 60% to cephalotin,
      45% to amikacin, 16% to cephotaxime, and 10% to pefloxacin, while 100% were
      susceptible to ceftriaxone. The V. alginolyticus strains isolated from oysters
      showed multiple resistance to antibiotics and several virulence factors described
      in well-characterized pathogenic vibrios. [Int Microbiol 19(4):191-198 (2016)].

PMID- 28504817
TI  - Biofilm formation in catheter-related infections by Panton-Valentine leukocidin
      producing Staphylococcus aureus.
AB  - The use of invasive techniques, such as intravascular catheter insertion, and the
      formation of biofilms in several devices by methicillin-resistant Staphylococcus
      aureus (MRSA) have contributed to the increased number of septic patients,
      morbidity and mortality. This study aimed to evaluate the virulence of strains
      through catheter colonization and identification of microbial biofilm, as well as
      pathological changes on the colonized skin. An experimental biofilm formation
      model utilized catheter fragments implanted subcutaneously in 25 Swiss mice. The
      technique consisted of inoculating a catheter fragment on the back of each
      animal, followed by intradermal inoculation of 50 MUl of bacterial suspension at
      1.0 * 107 colony forming units/ml. After 96 h, catheters were removed for
      macroscopic analysis and evaluated through culture. Local skin fragments were
      also extracted for histopathology analysis. Staphylococcus aureus can adhere to
      catheters, colonize and form biofilms. The high amount of viable bacterial cells
      colonizing catheters and virulence factors can lead to severe infections of skin
      and adjacent tissues. [Int Microbiol 19(4): 199-207 (2016)].

PMID- 28504819
TI  - Population-based cohort study of the effect of endometrial cancer classification
      and treatment criteria on long-term survival.
AB  - OBJECTIVE: To evaluate if increased individualization in endometrial cancer
      classification/treatment affected relative survival. METHODS: The present
      retrospective register-based population study included data from all women in the
      western Swedish healthcare region who were treated for endometrial cancer between
      January 1, 1995, and December 31, 2011. Outcomes and prognostic data were
      retrieved from the western Swedish healthcare region's cancer and clinical
      endometrial cancer registries. Patients were stratified based on two different
      treatment programs (cohort 1 January 1, 1995, to September 10, 2006, and cohort 2
      September 11, 2006, to December 31, 2011) and relative survival was compared.
      RESULTS: Data from 4338 patients were included; 2936 in cohort 1 and 1402 in
      cohort 2. Among endometrioid endometrial carcinomas, the 5-year relative survival
      rate for did not differ significantly between the groups (P=0.751); radiotherapy
      was used more frequently in cohort 1 (P<0.001). Among non-endometrioid
      endometrial carcinomas, relative survival was lower in cohort 1 (P=0.006);
      radiotherapy use was more frequent in cohort 1 and chemotherapy use was more
      frequent in cohort 2 (P=0.001). CONCLUSION: Increased individualization in
      endometrioid endometrial cancer management did not improve relative survival.
      Improved relative survival was observed for non-endometrioid endometrial cancer;
      possibly due to increased adjuvant chemotherapy use. This article is protected by
      copyright. All rights reserved.

PMID- 28504818
TI  - Characterization of Escherichia coli clinical isolates causing urinary tract
      infections in the community of Chilpancingo, Mexico.
AB  - Escherichia coli is the main cause of urinary tract infections (UTI) in
      ambulatory patients, especially strains belonging to the B2 phylogenetic group
      and ST131 clonal group. Antibiotic treatment is usually administered empirically;
      however, it is not always effective due to bacterial multidrug resistance and the
      production of extended spectrum beta-lactamases (ESBLs). The aim of this study
      was to characterize E. coli clinical isolates from patients with UTI in a
      community of the State of Guerrero, Mexico. From January to August 2014, 134
      clinical isolates of E. coli were recovered. Strain identification and antibiotic
      susceptibility were performed using the Vitek automated system. Phylogenetic and
      O25b-ST13 groups were determined by multiple PCR. Identification of the blaCTX-M,
      blaTEM, and blaSHV genes was performed by conventional PCR. We found that over
      50% of the isolates were resistant to betalactams and quinolones, while 0 to 33%
      were resistant to aminoglycosides and nitrofurans, and 56.49% of the strains were
      ESBL producers. B2 phylogenetic group was the most predominant (43%) compared to
      the other groups. The prevalence of bla genes was: blaCTX-M 64.3%, blaSHV 41.4%,
      and blaTEM 54.3%. These results show a high percentage (55%) of multidrug
      resistant strains isolated from UTI patients from the community in the city of
      Chilpancingo, Guerrero, Mexico. [Int Microbiol 19(4): 209-215 (2016)].

PMID- 28504821
TI  - Why you cannot transform your way out of trouble for small counts.
AB  - While data transformation is a common strategy to satisfy linear modeling
      assumptions, a theoretical result is used to show that transformation cannot
      reasonably be expected to stabilize variances for small counts. Under broad
      assumptions, as counts get smaller, it is shown that the variance becomes
      proportional to the mean under monotonic transformations g(.) that satisfy
      g(0)=0, excepting a few pathological cases. A suggested rule-of-thumb is that if
      many predicted counts are less than one then data transformation cannot
      reasonably be expected to stabilize variances, even for a well-chosen
      transformation. This result has clear implications for the analysis of counts as
      often implemented in the applied sciences, but particularly for multivariate
      analysis in ecology. Multivariate discrete data are often collected in ecology,
      typically with a large proportion of zeros, and it is currently widespread to use
      methods of analysis that do not account for differences in variance across
      observations nor across responses. Simulations demonstrate that failure to
      account for the mean-variance relationship can have particularly severe
      consequences in this context, and also in the univariate context if the sampling
      design is unbalanced.

PMID- 28504823
TI  - Centrifugal-driven, reduced-dimension, planar chromatography.
AB  - A fundamental problem with efficiency in capillary action driven planar
      chromatography results from diminishing flow rates as development proceeds,
      giving rise to molecular diffusion related band dispersion for most sample types.
      Overpressure and electrokinetic means to speed flow have been used successfully
      in TLC. We explore the use of centrifugal force (CF) to drive flow for reduced
      dimension planar platforms (ultra-TLC, low micrometer features, and nano-TLC,
      nanoscale features). The silicon wafer platforms have two forms of continuous 2D
      arrays created by either photolithography or metal dewetting followed by deep
      reactive ion etching and coated with porous SiO2 . The flow pattern is unusual
      with co-planar flows above and within the arrays. The effects of parameters such
      as spin rate, solvent type, and surface character on flow rates is established
      and can be substantially greater than capillary action flow. Using fluorescent
      dyes, we investigate retardation factors and chromatographic plate height; the
      latter falls in the low to sub-micrometer range. To the best of our knowledge, we
      demonstrate the first analytical separations performed in pillar arrays using CF
      to augment solvent flow.

PMID- 28504822
TI  - Equilibrium, Kinetic and Structural Properties of Gallium(III) and Some Divalent
      Metal Complexes Formed with the New DATAm and DATA5m Ligands.
AB  - The development of 68 Ge/68 Ga generators has made the positron-emitting 68 Ga
      isotope widely accessible and raised interest in new chelate complexes of Ga3+ .
      The hexadentate 1,4-di(acetate)-6-methyl[amino(methyl)acetate]perhydro-1,4
      diazepane (DATAm ) ligand and its bifunctional analogue, 1,4-di(acetate)-6
      pentanoic acid[amino(methyl)acetate]perhydro-1,4-diazepane (DATA5m ), rapidly
      form complexes with 68 Ga in high radiochemical yield. The stability constants of
      DATAm and DATA5m complexes formed with Ga3+ , Zn2+ , Cu2+ , Mn2+ and Ca2+ have
      been determined by using pH potentiometry, spectrophotometry (Cu2+ ) and 1 H and
      71 Ga NMR spectroscopy (Ga3+ ). The stability constants of Ga(DATAm ) and
      Ga(DATA5m ) complexes are slightly higher than those of Ga(AAZTA). The species
      distribution calculations indicated the predominance of Ga(L)OH mixed-hydroxo
      complexes at physiological pH. The 1 H and 71 Ga NMR spectroscopy studies
      provided information about the coordinated functional groups of ligands and on
      the kinetics of exchange between the Ga(L) and Ga(L)OH complexes. The
      transmetalation reactions between the Ga(L) complexes and Cu2+ citrate (6<pH<8.5)
      occur through both spontaneous and OH- -assisted dissociation of the Ga(L)OH
      species. At pH 7.4 and 25  degrees C, the half-lives of the dissociation of
      Ga(DATAm ), Ga(DATA5m ) and Ga(AAZTA) were 11, 44 and 24 h, respectively. Similar
      half-lives have been obtained for the ligand-exchange reactions between the
      Ga(L)OH complexes and transferrin. The equilibrium and kinetic data indicate that
      the Ga(DATA5m ) complex is a good 68 Ga-based radiodiagnostic candidate.

PMID- 28504824
TI  - Thyroid function after TSH suppression for thyroid cancer: When is optimal time
      to check?

PMID- 28504825
TI  - One-step simultaneous detection of Ureaplasma parvum and genotypes SV1, SV3 and
      SV6 from clinical samples using PlexPCR technology.
AB  - : Ureaplasma spp. are associated with preterm birth. In recent times, it has
      become apparent that Ureaplasma parvum, but not Ureaplasma urealyticum, is of
      most relevance. We recently demonstrated this in Australian pregnant women and
      using high-resolution melt (HRM) PCR, further showed that U. parvum genotype SV6
      was of particular significance. However, our assay was unable to identify
      multiple genotypes in the same sample, required a separate species-level qPCR for
      low titre samples and was not ideal for diagnostic laboratories due to the nature
      of HRM PCR result interpretation. Consequently, our current study developed a
      novel, one-step PlexPCR assay capable of detecting U. parvum and genotypes SV1,
      SV3 and SV6 in a single reaction directly from clinical samples. We then
      validated this using vaginal swab DNA from our Australian cohort of pregnant
      women. The PlexPCR was highly sensitive, detecting all targets to between 0.4 *
      10-5  ng DNA (SV3) and 0.4 * 10-6  ng DNA (U. parvum, SV1 and SV6). Compared to
      our HRM PCR, the PlexPCR defined genotype distribution in all seven cases
      previously reported as 'mixed', and detected another eight cases where multiple
      genotypes (two) were present in samples previously reported as single genotypes
      using HRM PCR. SIGNIFICANCE AND IMPACT OF THE STUDY: Ureaplasma spp. have been
      associated with prematurity for decades, however, only a minority of studies have
      examined this beyond the genus level. In those that have, Ureaplasma parvum has
      been strongly associated with preterm birth. We recently demonstrated this in
      Australian women and further showed that U. parvum genotype SV6 was of particular
      significance. Our PlexPCR assay allows rapid detection and concurrent genotyping
      of U. parvum in clinical samples and may be of particular interest to
      obstetricians, particularly those caring for women at a high risk of preterm
      birth, and any other disease phenotypes where U. parvum is of interest.

PMID- 28504826
TI  - Pigmented macules in Waardenburg syndrome type 2 due to KITLG mutation.

PMID- 28504827
TI  - A homozygous missense mutation in SLC25A16 associated with autosomal recessive
      isolated fingernail dysplasia in a Pakistani family.

PMID- 28504828
TI  - Improvement in solvent tolerance by exogenous glycerol in Pseudomonas sp. BCNU
      106.
AB  - : Solvent hypertolerant Pseudomonas sp. BCNU 106 still has some underlying growth
      limitation in solvents. Therefore, efficient mass cultivation methods are needed
      to pursue its applications in biotechnology. Pseudomonas sp. BCNU 106 was
      cultured in a medium supplemented with 0.05 mol l-1 glycerol and cell survival
      was monitored during its cultivation in the presence of 1% (v/v) toluene.
      Exogenously supplemented glycerol provided more protection against damage caused
      by toluene stress and conferred higher solvent tolerance of Pseudomonas sp. BCNU
      106 to toluene compared to control Pseudomonas sp. BCNU 106 without the
      supplementation of glycerol. This low-cost mass cultivation method can be used to
      efficiently apply solvent-tolerant bacteria in biotransformation and
      biodegradation. SIGNIFICANCE AND IMPACT OF THE STUDY: Protection against toluene
      and improvement in bacterial cell growth by supplementation of glycerol in the
      presence of toluene are demonstrated in this study. This result can be used to
      solve growth-related hindrances of solvent-tolerant bacteria and establish their
      low-cost mass cultivation, thereby broadening their industrial and environmental
      applications.

PMID- 28504829
TI  - Prediction of thrombophilia in patients with unexplained recurrent pregnancy loss
      using a statistical model.
AB  - OBJECTIVE: To establish a statistical model to predict thrombophilia in patients
      with unexplained recurrent pregnancy loss (URPL). METHODS: A retrospective case
      control study was conducted at Ren Ji Hospital, Shanghai, China, from March 2014
      to October 2016. The levels of D-dimer (DD), fibrinogen degradation products
      (FDP), activated partial thromboplastin time (APTT), prothrombin time (PT),
      thrombin time (TT), fibrinogen (Fg), and platelet aggregation in response to
      arachidonic acid (AA) and adenosine diphosphate (ADP) were collected. Receiver
      operating characteristic curve analysis was used to analyze data from 158 UPRL
      patients (>=3 previous first trimester pregnancy losses with unexplained
      etiology) and 131 non-RPL patients (no history of recurrent pregnancy loss). A
      logistic regression model (LRM) was built and the model was externally validated
      in another group of patients. RESULTS: The LRM included AA, DD, FDP, TT, APTT,
      and PT. The overall accuracy of the LRM was 80.9%, with sensitivity and
      specificity of 78.5% and 78.3%, respectively. The diagnostic threshold of the
      possibility of the LRM was 0.6492, with a sensitivity of 78.5% and a specificity
      of 78.3%. Subsequently, the LRM was validated with an overall accuracy of 83.6%.
      CONCLUSION: The LRM is a valuable model for prediction of thrombophilia in URPL
      patients.

PMID- 28504830
TI  - Exploring Planar-Chiral Amino Siloxides.
AB  - We present the synthesis, structure, and exemplary reactivity of siloxides with a
      planar-chiral N,N-dimethylaminomethylferrocene backbone. Several zinc complexes
      based on the racemic as well as the enantiomerically pure silanol were
      synthesized in the presence of water and crystallographically characterized, and
      their behavior in solution was examined. The chiral probe present in this system
      is a valuable tool for identifying the structure in solution. Furthermore, the
      zinc siloxides exhibit a comparable reactivity to the corresponding silanols.
      Therefore, they can be regarded as "masked" silanols, especially when the
      silanols are preparatively inaccessible.

PMID- 28504831
TI  - From Discrete Molecular Cages to a Network of Cages Exhibiting Enhanced CO2
      Adsorption Capacity.
AB  - We have adopted the concept of "cage to frameworks" to successfully produce a Na
      N connected coordination networked cage Na-NC1 by using a [3+6] porous imine
      linked organic cage NC1 (Nanjing Cage 1) as the precursor. It is found that Na
      NC1 exhibits hierarchical porosity (inherent permanent voids and interconnected
      channel) and gas sorption measurements reveal a significantly enhanced CO2 uptake
      (1093 cm3  g-1 at 23 bar and 273 K) than that of NC1 (162 cm3  g-1 under the same
      conditions). In addition, Na-NC1 exhibits very low CO2 adsorption enthalpy making
      it a good candidate for porous materials with both high CO2 storage and low
      adsorption enthalpy.

PMID- 28504832
TI  - Observation of Supramolecular Chirality in a Hierarchically Self-Assembled Mixed
      Stack Charge-Transfer Complex.
AB  - Supramolecular chirality was observed in a charge-transfer (CT) complex formed by
      self-assembly of beta-cyclodextrin-linked pyrene and adamantane-linked
      pyromellitic diimide in water. In the complex, the pyrene-pyromellitic diimide CT
      interaction is reinforced several-fold by the strong beta-cyclodextrin-adamantane
      inclusion binding interaction, as confirmed by 1 H NMR, absorption, fluorescence
      and isothermal titration calorimetry studies. The CT complex exhibited high
      stability, as inferred from the temperature-dependent absorption and NMR studies.
      The CT absorption band exhibited a positive Cotton effect indicative of
      supramolecular chirality for the complex. Twisted fibres were observed in TEM,
      AFM, and SEM experiments. A mechanism involving synergistic binding interactions
      leading to 2D sheets, followed by twisting of the sheet, is proposed for the
      formation of twisted fibres. This system offers a chance to investigate a
      combination of supramolecular CT and supramolecular chirality and explore their
      synergistic effects.

PMID- 28504833
TI  - The role of men in induced abortion decision making in an urban area of the
      Philippines.
AB  - OBJECTIVE: To understand beliefs about unintended pregnancy and abortion, and
      perceptions about male roles related to pregnancy decision-making among men in
      the Philippines. METHODS: Qualitative data were collected during in-depth
      interviews and focus group discussions with men in an urban area of the
      Philippines between October 2007 and July 2008. Interview participants were
      purposively sampled from a local survey based on their having reported being
      "afraid or troubled" or "afraid and planned to terminate" in response to a recent
      pregnancy. Focus group participants were selected from the same communities. Data
      were analyzed using the constant comparative method. RESULTS: In-depth interview
      data from 15 men-each interviewed twice-and five focus group discussions were
      included. Male interview participants reported feeling morally responsible for
      the pregnancy and as wanting to avoid the "sin" of induced abortion; however,
      they were concerned about being able to support a family financially.
      Participants expressed resentment towards partners who attempted or completed an
      induced abortion without their knowledge. In such cases, men would disparage
      their partner and cease interacting with them to avoid the "sin" of induced
      abortion. CONCLUSION: Participants described negative feelings towards women
      seeking induced abortions, and their own desire to avoid associated "sin". This
      highlights the effects of unintended pregnancy and induced abortion on young
      Filipino men, including their own experience of abortion stigma.

PMID- 28504834
TI  - Resource stoichiometry and availability modulate species richness and biomass of
      tropical litter macro-invertebrates.
AB  - High biodiversity and biomass of soil communities are crucial for litter
      decomposition in terrestrial ecosystems such as tropical forests. However, the
      leaf litter that these communities consume is of particularly poor quality as
      indicated by elemental stoichiometry. The impact of resource quantity, quality
      and other habitat parameters on species richness and biomass of consumer
      communities is often studied in isolation, although much can be learned from
      simultaneously studying both community characteristics. Using a dataset of 780
      macro-invertebrate consumer species across 32 sites in tropical lowland rain
      forest and agricultural systems on Sumatra, Indonesia, we investigated the
      effects of basal resource stoichiometry (C:X ratios of N, P, K, Ca, Mg, Na, S in
      local leaf litter), litter mass (basal resource quantity and habitat space),
      plant species richness (surrogate for litter habitat heterogeneity), and soil pH
      (acidity) on consumer species richness and biomass across different consumer
      groups (i.e. 3 feeding guilds and 10 selected taxonomic groups). In order to
      distinguish the most important predictors of consumer species richness and
      biomass, we applied a standardised model averaging approach investigating the
      effects of basal resource stoichiometry, litter mass, plant species richness and
      soil pH on both consumer community characteristics. This standardised approach
      enabled us to identify differences and similarities in the magnitude and
      importance of such effects on consumer species richness and biomass. Across
      consumer groups, we found litter mass to be the most important predictor of both
      species richness and biomass. Resource stoichiometry had a more pronounced impact
      on consumer species richness than on their biomass. As expected, taxonomic groups
      differed in which resource and habitat parameters (basal resource stoichiometry,
      litter mass, plant species richness and pH) were most important for modulating
      their community characteristics. The importance of litter mass for both species
      richness and biomass indicates that these tropical consumers strongly depend on
      habitat space and resource availability. Our study supports previous theoretical
      work indicating that consumer species richness is jointly influenced by resource
      availability and the balanced supply of multiple chemical elements in their
      resources.

PMID- 28504835
TI  - Electronic and Ligand Properties of Skeletally Substituted Cyclic
      (Alkyl)(Amino)Carbenes (CAACs) and Their Reactivity towards Small Molecule
      Activation: A Theoretical Study.
AB  - Quantum chemical calculations have been carried out to understand the ligand
      properties of skeletally modified cyclic alkyl amino carbenes. The stability of
      these carbenes has been assessed from an evaluation of their singlet-triplet and
      stabilization energy values. Ylide substituted carbenes are found to be more
      stable than non-ylidic ones in their optimized singlet state. Nucleophilicity and
      electrophilicity indices values were evaluated in order to further investigate
      the reactivity of these carbenes. The calculated values of proton affinities and
      the degree of gallium pyramidalization in the carbene-GaCl3 adducts correlate
      well with the sigma-basicity of these carbenes. The reactivity of non-ylidic
      carbenes toward the activation of both H2 and NH3 are calculated to be more
      favourable compared to that of parent CAAC. On the other hand, ylide anchored
      carbenes are found to be unsuccessful toward the activation of both H2 and NH3 .

PMID- 28504836
TI  - Simple and fast overidentified rank estimation for right-censored length-biased
      data and backward recurrence time.
AB  - Length-biased survival data subject to right-censoring are often collected from a
      prevalent cohort. However, informative right censoring induced by the sampling
      design creates challenges in methodological development. While certain
      conditioning arguments could circumvent the problem of informative censoring,
      related rank estimation methods are typically inefficient because the marginal
      likelihood of the backward recurrence time is not ancillary. Under a
      semiparametric accelerated failure time model, an overidentified set of log-rank
      estimating equations is constructed based on the left-truncated right-censored
      data and backward recurrence time. Efficient combination of the estimating
      equations is simplified by exploiting an asymptotic independence property between
      two sets of estimating equations. A fast algorithm is studied for solving non
      smooth, non-monotone estimating equations. Simulation studies confirm that the
      overidentified rank estimator can have a substantially improved estimation
      efficiency compared to just-identified rank estimators. The proposed method is
      applied to a dementia study for illustration.

PMID- 28504837
TI  - Immunotherapy for metastatic renal cell carcinoma.
AB  - BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma
      (mRCC) has experienced a paradigm shift from non-specific therapy with broad
      acting cytokines to specific regimens, which directly target the cancer, the
      tumour microenvironment, or both.Current guidelines recommend targeted therapies
      with agents such as sunitinib, pazopanib or temsirolimus (for people with poor
      prognosis) as the standard of care for first-line treatment of people with mRCC
      and mention non-specific cytokines as an alternative option for selected
      patients.In November 2015, nivolumab, a checkpoint inhibitor directed against
      programmed death-1 (PD-1), was approved as the first specific immunotherapeutic
      agent as second-line therapy in previously treated mRCC patients. OBJECTIVES: To
      assess the effects of immunotherapies either alone or in combination with
      standard targeted therapies for the treatment of metastatic renal cell carcinoma
      and their efficacy to maximize patient benefit. SEARCH METHODS: We searched the
      Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers
      of ongoing clinical trials in November 2016 without language restrictions. We
      scanned reference lists and contacted experts in the field to obtain further
      information. SELECTION CRITERIA: We included randomized controlled trials (RCTs)
      and quasi-RCTs with or without blinding involving people with mRCC. DATA
      COLLECTION AND ANALYSIS: We collected and analyzed studies according to the
      published protocol. Summary statistics for the primary endpoints were risk ratios
      (RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We
      rated the quality of evidence using GRADE methodology and summarized the quality
      and magnitude of relative and absolute effects for each primary outcome in our
      'Summary of findings' tables. MAIN RESULTS: We identified eight studies with 4732
      eligible participants and an additional 13 ongoing studies. We categorized
      studies into comparisons, all against standard therapy accordingly as first-line
      (five comparisons) or second-line therapy (one comparison) for mRCC.Interferon
      (IFN)-alpha monotherapy probably increases one-year overall mortality compared to
      standard targeted therapies with temsirolimus or sunitinib (RR 1.30, 95% CI 1.13
      to 1.51; 2 studies; 1166 participants; moderate-quality evidence), may lead to
      similar quality of life (QoL) (e.g. MD -5.58 points, 95% CI -7.25 to -3.91 for
      Functional Assessment of Cancer - General (FACT-G); 1 study; 730 participants;
      low-quality evidence) and may slightly increase the incidence of adverse events
      (AEs) grade 3 or greater (RR 1.17, 95% CI 1.03 to 1.32; 1 study; 408
      participants; low-quality evidence).There is probably no difference between IFN
      alpha plus temsirolimus and temsirolimus alone for one-year overall mortality (RR
      1.13, 95% CI 0.95 to 1.34; 1 study; 419 participants; moderate-quality evidence),
      but the incidence of AEs of 3 or greater may be increased (RR 1.30, 95% CI 1.17
      to 1.45; 1 study; 416 participants; low-quality evidence). There was no
      information on QoL.IFN-alpha alone may slightly increase one-year overall
      mortality compared to IFN-alpha plus bevacizumab (RR 1.17, 95% CI 1.00 to 1.36; 2
      studies; 1381 participants; low-quality evidence). This effect is probably
      accompanied by a lower incidence of AEs of grade 3 or greater (RR 0.77, 95% CI
      0.71 to 0.84; 2 studies; 1350 participants; moderate-quality evidence). QoL could
      not be evaluated due to insufficient data.Treatment with IFN-alpha plus
      bevacizumab or standard targeted therapy (sunitinib) may lead to similar one-year
      overall mortality (RR 0.37, 95% CI 0.13 to 1.08; 1 study; 83 participants; low
      quality evidence) and AEs of grade 3 or greater (RR 1.18, 95% CI 0.85 to 1.62; 1
      study; 82 participants; low-quality evidence). QoL could not be evaluated due to
      insufficient data.Treatment with vaccines (e.g. MVA-5T4 or IMA901) or standard
      therapy may lead to similar one-year overall mortality (RR 1.10, 95% CI 0.91 to
      1.32; low-quality evidence) and AEs of grade 3 or greater (RR 1.16, 95% CI 0.97
      to 1.39; 2 studies; 1065 participants; low-quality evidence). QoL could not be
      evaluated due to insufficient data.In previously treated patients, targeted
      immunotherapy (nivolumab) probably reduces one-year overall mortality compared to
      standard targeted therapy with everolimus (RR 0.70, 95% CI 0.56 to 0.87; 1 study;
      821 participants; moderate-quality evidence), probably improves QoL (e.g. RR
      1.51, 95% CI 1.28 to 1.78 for clinically relevant improvement of the FACT-Kidney
      Symptom Index Disease Related Symptoms (FKSI-DRS); 1 study, 704 participants;
      moderate-quality evidence) and probably reduces the incidence of AEs grade 3 or
      greater (RR 0.51, 95% CI 0.40 to 0.65; 1 study; 803 participants; moderate
      quality evidence). AUTHORS' CONCLUSIONS: Evidence of moderate quality
      demonstrates that IFN-alpha monotherapy increases mortality compared to standard
      targeted therapies alone, whereas there is no difference if IFN is combined with
      standard targeted therapies. Evidence of low quality demonstrates that QoL is
      worse with IFN alone and that severe AEs are increased with IFN alone or in
      combination. There is low-quality evidence that IFN-alpha alone increases
      mortality but moderate-quality evidence on decreased AEs compared to IFN-alpha
      plus bevacizumab. Low-quality evidence shows no difference for IFN-alpha plus
      bevacizumab compared to sunitinib with respect to mortality and severe AEs. Low
      quality evidence demonstrates no difference of vaccine treatment compared to
      standard targeted therapies in mortality and AEs, whereas there is moderate
      quality evidence that targeted immunotherapies reduce mortality and AEs and
      improve QoL.

PMID- 28504840
TI  - Clinical utility of a short resting-state MRI scan in differentiating bipolar
      from unipolar depression.
AB  - OBJECTIVE: Depression in bipolar disorder (BipD) requires a therapeutic approach
      that is from treating unipolar major depressive disorder (UniD), but to date, no
      reliable methods could separate these two disorders. The aim of this study was to
      establish the clinical validity and utility of a non-invasive functional MRI
      based method to classify BipD from UniD. METHOD: The degree of connectivity
      (degree centrality or DC) of every small unit (voxel) with every other unit of
      the brain was estimated in 22 patients with BipD and 22 age, gender, and
      depressive severity-matched patients with UniD and 22 healthy controls. Pattern
      classification analysis was carried out using a support-vector machine (SVM)
      approach. RESULTS: Degree centrality pattern from 8-min resting fMRI
      discriminated BipD from UniD with an accuracy of 86% and diagnostic odds ratio of
      9.6. DC was reduced in the left insula and increased in bilateral precuneus in
      BipD when compared to UniD. In this sample with a high degree of uncertainty (50%
      prior probability), positive predictive value of the DC test was 79%. CONCLUSION:
      Degree centrality maps are potential candidate measures to separate bipolar
      depression from unipolar depression. Test performance reported here requires
      further pragmatic evaluation in regular clinical practice.

PMID- 28504839
TI  - The pathological Trento variant of alpha-1-antitrypsin (E75V) shows nonclassical
      behaviour during polymerization.
AB  - Severe alpha-1-antitrypsin deficiency (AATD) is most frequently associated with
      the alpha-1-antitrypsin (AAT) Z variant (E342K). ZZ homozygotes exhibit
      accumulation of AAT as polymers in the endoplasmic reticulum of hepatocytes. This
      protein deposition can lead to liver disease, with the resulting low circulating
      levels of AAT predisposing to early-onset emphysema due to dysregulation of
      elastinolytic activity in the lungs. An increasing number of rare AAT alleles
      have been identified in patients with severe AATD, typically in combination with
      the Z allele. Here we report a new mutation (E75V) in a patient with severe
      plasma deficiency, which we designate Trento. In contrast to the Z mutant, Trento
      AAT was secreted efficiently when expressed in cellular models but showed
      compromised conformational stability. Polyacrylamide gel electrophoresis (PAGE)
      and ELISA-based analyses of the secreted protein revealed the presence of
      oligomeric species with electrophoretic and immunorecognition profiles different
      from those of Z and S (E264V) AAT polymers, including reduced recognition by
      conformational monoclonal antibodies 2C1 and 4B12. This altered recognition was
      not due to direct effects on the epitope of the 2C1 monoclonal antibody which we
      localized between helices E and F. Structural analyses indicate the likely basis
      for polymer formation is the loss of a highly conserved stabilizing interaction
      between helix C and the posthelix I loop. These results highlight this region as
      important for maintaining native state stability and, when compromised, results
      in the formation of pathological polymers that are different from those produced
      by Z and S AAT.

PMID- 28504841
TI  - Chemical Composition, Antibacterial, Schistosomicidal, and Cytotoxic Activities
      of the Essential Oil of Dysphania ambrosioides (L.) Mosyakin & Clemants
      (Chenopodiaceae).
AB  - We have investigated the chemical composition and the antibacterial activity of
      the essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants
      (Chenopodiaceae) (DA-EO) against a representative panel of cariogenic bacteria.
      We have also assessed the in vitro schistosomicidal effects of DA-EO on
      Schistosoma mansoni and its cytotoxicity to GM07492-A cells in vitro. Gas
      chromatography (GC) and gas chromatography-mass spectrometry (GC/MS) revealed
      that the monoterpenes cis-piperitone oxide (35.2%), p-cymene (14.5%),
      isoascaridole (14.1%), and alpha-terpinene (11.6%) were identified by as the
      major constituents of DA-EO. DA-EO displayed weak activity against Streptococcus
      sobrinus and Enterococcus faecalis (minimum inhibitory concentration (MIC) = 1000
      MUg/ml). On the other hand, DA-EO at 25 and 12.5 MUg/ml presented remarkable
      schistosomicidal action in vitro and killed 100% of adult worm pairs within 24
      and 72 h, respectively. The LC50 values of DA-EO were 6.50 +/- 0.38, 3.66 +/-
      1.06, and 3.65 +/- 0.76 MUg/ml at 24, 48, and 72 h, respectively. However, DA-EO
      at concentrations higher than 312.5 MUg/ml significantly reduced the viability of
      GM07492-A cells (IC50  = 207.1 +/- 4.4 MUg/ml). The selectivity index showed that
      DA-EO was 31.8 times more toxic to the adult S. mansoni worms than GM07492-A
      cells. Taken together, these results demonstrate the promising schistosomicidal
      potential of the essential oil of Dysphania ambrosioides.

PMID- 28504838
TI  - Human innate lymphoid cells (ILCs) in filarial infections.
AB  - Filarial infections are characteristically chronic and can cause debilitating
      diseases governed by parasite-induced innate and adaptive immune responses.
      Filarial parasites traverse or establish niches in the skin (migrating infective
      larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin
      (circulating microfilariae) where they intersect with the host immune response.
      While several studies have demonstrated that filarial parasites and their
      antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell
      subsets), T- and B-lymphocytes and skin resident cell populations, the role of
      innate lymphoid cells during filarial infections has only recently emerged.
      Despite the identification and characterization of innate lymphoid cells (ILCs)
      in murine helminth infections, little is actually known about the role of human
      ILCs during parasitic infections. The focus of this review will be to highlight
      the composition of ILCs in the skin, lymphatics and blood; where the host
      parasite interaction is well-defined and to examine the role of ILCs during
      filarial infections.

PMID- 28504844
TI  - Naphthalimide-Based Polyammonium Chemosensors for Anions: Study of Binding
      Properties and Sensing Mechanisms.
AB  - New naphthalimide-based receptors for anions have been synthesized. Efficient
      synthetic routes have been discovered to functionalize the naphthalimide core
      with branched polyamines. Binding and sensing properties of the receptors were
      studied by potentiometric, NMR and fluorescence titrations. The receptors bind
      selectively to the pyrophosphate anion in buffered aqueous solutions. The
      receptors with more than six amine groups in the structure demonstrated the
      highest affinities for pyrophosphate. The fluorescence response towards anions
      was found to be dependent on the position of the amine groups relative to the
      naphthalimide core, and on the pH of the buffered solution. Three sensing
      mechanisms have been found that explain fluorescence responses of receptors
      towards anions in an aqueous solution.

PMID- 28504843
TI  - A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in
      an in vivo rat model of oxidative stress.
AB  - In this study, we tested a novel synthetic pyrazole-containing compound, 5-amino
      1-phenyl-1H-pyrazole-4-carbonitrile (APPC), as an antioxidant in both in vitro
      and in vivo models of oxidative stress. In addition, the utility of covalently
      combining APPC with another well-established antioxidant, lipoic acid (LA), was
      also tested in both models. The in vitro results demonstrated that pretreatment
      with APPC in a mixed neuronal-glial culture exposed to oxygen-glucose deprivation
      (OGD) followed by reoxygenation-refeeding, resulted in significant
      neuroprotection at concentrations between 2.5 to 25 MUmol/L. In contrast, LA was
      not neuroprotective following OGD alone or following reoxygenation-refeeding.
      However, the synthetic covalent combination of APPC with LA, named "UPEI-800",
      resulted in significant neuroprotection at concentrations between 0.027 and 2.7
      MUmol/L (100-fold more potent than APPC alone), an effect shown to be correlated
      with increased cellular antioxidant capacity. Further, in an in vivo model of
      ischaemia-reperfusion injury following transient occlusion of the middle cerebral
      artery (tMCAO), both APPC (0.1 and 1.0 mg/kg) and UPEI-800 (1*10-3  mg/kg)
      provided significant neuroprotection. Consistent with the in vitro findings, the
      in vivo results following tMCAO also demonstrated a 100-fold increase in the
      potency of the covalently linked compound UPEI-800 compared to APPC alone.

PMID- 28504842
TI  - Safety and efficacy of current direct-acting antiviral regimens in kidney and
      liver transplant recipients with hepatitis C: Results from the HCV-TARGET study.
AB  - : Data outside of clinical trials with direct-acting antiviral regimens with or
      without ribavirin as treatment of chronic hepatitis C virus in solid organ
      transplant recipients are limited. Liver transplant (LT), kidney transplant (KT),
      and dual liver kidney (DLK) transplant recipients from the Hepatitis C
      Therapeutic Registry and Research Network database, a multicenter, longitudinal
      clinical care treatment cohort, treated with direct-acting antiviral regimens
      between January 1, 2014, and February 15, 2016, were included to assess safety
      and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK =
      36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had
      genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were
      treated with sofosbuvir (SOF)/ledipasvir +/- ribavirin (85%) followed by SOF +
      daclatasvir +/- ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir
      +/- ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were
      available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks:
      96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients,
      respectively. Ribavirin did not influence SVR rates and was more often used in
      those with higher BMI, higher estimated glomerular filtration rate and lower
      creatinine. Female gender, baseline albumin >=3.5 g/dL, baseline total bilirubin
      <=1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12
      weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during
      hepatitis C virus treatment in 4 and after cessation of treatment in 2.
      CONCLUSION: In a large prospective observational cohort study, direct-acting
      antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir +
      dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK
      transplant recipients; ribavirin did not influence SVR, and graft rejection was
      rare. (Hepatology 2017;66:1090-1101).

PMID- 28504845
TI  - Rhodium(I)-Catalyzed Tertiary Phosphine Directed C-H Arylation: Rapid
      Construction of Ligand Libraries.
AB  - Modification of commercially available monophosphine ligands with either aryl
      bromides or chlorides by rhodium(I)-catalyzed, tertiary phosphine directed C-H
      activation is described. A series of ligand libraries containing mono- and diaryl
      substituted groups, having different steric and electronic properties, were
      obtained in high yields. Based on the outstanding properties of their parent
      scaffolds, the modified ligands have been found to be powerful in organic
      reactions.

PMID- 28504847
TI  - Implementation of a digital preparation validation tool in dental skills
      laboratory training.
AB  - AIM: To describe the implementation of a digital tool for preparation validation
      and evaluate it as an aid in students' self-assessment. METHODS: Students at the
      final semester of skills laboratory training were asked to use a digital
      preparation validation tool (PVT) when performing two different tasks;
      preparation of crowns for teeth 11 and 21. The students were divided into two
      groups. Group A self-assessed and scanned all three attempts at 21 ("prep-and
      scan"). Group B self-assessed all attempts chose the best one and scanned it
      ("best-of-three"). The situation was reversed for 11. The students assessed five
      parameters of the preparation and marked them as approved (A) or failed (F).
      These marks were compared with the information from the PVT. The students also
      completed a questionnaire. Each question was rated from 1 to 5. Teachers'
      opinions were collected at staff meetings throughout the project. RESULTS: Most
      students in the "prep-and-scan" groups showed an increase in agreement between
      their self-assessment and the information from the PVT, whereas students in the
      "best-of-three" groups showed lower levels of agreement. All students rated the
      PVT positively. Most strongly agreed that the tool was helpful in developing
      skills (mean 4.15), easy to use (mean 4.23) and that it added benefits in
      comparison to existing assessment tools (mean 4.05). They did not however, fully
      agree that the tool is time efficient (mean 2.55), and they did not consider it a
      substitute for verbal teacher feedback. Teachers' feedback suggested advantages
      of the tool in the form of ease of use, visual aid and increasing interest and
      motivation during skills laboratory training however, they did not notice a
      reduction in need of verbal feedback. CONCLUSIONS: Within the limitations of the
      study, our conclusion is that a digital PVT may be a valuable adjunct to other
      assessment tools in skills laboratory training.

PMID- 28504846
TI  - Adverse event management in patients with relapsed and refractory multiple
      myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.
AB  - OBJECTIVES: Heavily pretreated patients with relapsed and refractory multiple
      myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs
      are important to ensure patients continue therapy long enough to receive the best
      clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to
      further characterize the safety profile of pomalidomide plus low-dose
      dexamethasone and AE management. METHODS: This analysis included 1088 patients
      who received >= 2 prior therapies, including lenalidomide and bortezomib, and
      progressed <= 60 days of last therapy. Patients received 28-day cycles of
      pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if
      aged > 75 years) weekly until disease progression or unacceptable toxicity.
      Thromboprophylaxis was required. RESULTS: The most common grade 3/4 AEs were
      neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred
      within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7%
      patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide
      dose reductions or interruptions were reported in 24.2% and 66.0% of patients,
      respectively. AEs were managed by dose modifications and/or supportive care.
      CONCLUSIONS: Pomalidomide plus low-dose dexamethasone showed an acceptable safety
      profile, and AEs were well managed according to study protocols and established
      guidelines.

PMID- 28504848
TI  - Association of traumatic head injuries and maxillofacial fractures: A
      retrospective study.
AB  - BACKGROUND/AIMS: The association of traumatic head injury (THI) with
      maxillofacial fractures (MFF) is a major health concern worldwide. In spite of
      the close anatomical proximity of maxillofacial bones to the cranium, the
      association of THI with MFF is controversial. The aim of this study was to assess
      the association between THI and MFF. Other factors associated with THI in
      patients with MFF were also investigated. MATERIALS AND METHODS: A hospital-based
      retrospective study was conducted at the OMFS Unit, Hospital USM, Kelantan,
      Malaysia. From 12 June 2013 to 31 December 2015, 473 patient records with MFF
      were reviewed to evaluate the association of THI and MFF. RESULTS: A total of 331
      patients (69.98%) presented with concomitant THI. The most common associated THI
      were cranial bone fractures (68.6%) followed by intracranial injuries and
      concussion. A significant association existed between the Glasgow coma scale
      (GCS) score and the presence of THI concomitant MFF with P-value <.001. The
      univariable logistic regression analysis revealed that age group (31-40 years),
      cause of injury (road traffic accident-RTA), all midface fracture types and most
      of the mandibular fracture types were statistically associated with the presence
      of THI. The multivariable logistic regression analysis revealed that the cause of
      the injury (RTA) and MFF types (nasal bone, zygomatic complex, zygomatic arch,
      orbital wall, maxillary sinus wall and the alveolar process of mandible
      fractures) were statistically significantly associated with THI in patients with
      MFF. CONCLUSION: There was a high prevalence of THI among patients with MFF
      (69.98%). RTA, nasal bone, zygomatic complex, zygomatic arch, orbital wall,
      maxillary sinus wall and mandibular alveolar process fractures were significantly
      associated with THI in patients who sustained a MFF.

PMID- 28504849
TI  - Diagnosis and treatment of cervical papillary squamous cell carcinoma with
      unknown depth of stromal invasion.
AB  - OBJECTIVE: To evaluate the diagnosis and treatment of papillary squamous cell
      carcinoma (PSCC) of the uterine cervix with unknown depth of stromal invasion.
      METHODS: In a retrospective study, the diagnostic and treatment strategies after
      colposcopy-guided biopsy sampling were assessed among patients seen at a
      university hospital in Shanghai, China, in 2008-2015. RESULTS: Among 55 patients,
      29 with clinically visible lesions underwent radical hysterectomy; the final
      pathologic diagnosis was invasive squamous cell carcinoma in all patients. Of
      these patients, eight had undergone loop electrosurgical excision procedure
      (LEEP) and two had undergone a second biopsy sampling before radical hysterectomy
      was performed. Of the 26 patients with no clinically visible lesions, 17 had
      cervical lesions as confirmed by medical imaging and 12 of these patients
      underwent LEEP. The pathologic examination showed lesions of varying severity but
      no cancer in situ. The remaining five patients underwent radical hysterectomy;
      one of these patients was found to have micro-invasive cancer. CONCLUSION:
      Patients with PSCC with unknown depth of stromal invasion and clinically visible
      lesions receive radical hysterectomy rather than undergoing a second biopsy
      sampling or LEEP. Less invasive surgery is recommended for patients with no
      clinically visible lesions.

PMID- 28504851
TI  - Identification of bacterial guanylate cyclases.

PMID- 28504850
TI  - Visualizing Biological Copper Storage: The Importance of Thiolate-Coordinated
      Tetranuclear Clusters.
AB  - Bacteria possess cytosolic proteins (Csp3s) capable of binding large quantities
      of copper and preventing toxicity. Crystal structures of a Csp3 plus increasing
      amounts of CuI provide atomic-level information about how a storage protein loads
      with metal ions. Many more sites are occupied than CuI equiv added, with binding
      by twelve central sites dominating. These can form [Cu4 (S-Cys)4 ] intermediates
      leading to [Cu4 (S-Cys)5 ]- , [Cu4 (S-Cys)6 ]2- , and [Cu4 (S-Cys)5 (O-Asn)]-
      clusters. Construction of the five CuI sites at the opening of the bundle lags
      behind the main core, and the two least accessible sites at the opposite end of
      the bundle are occupied last. Facile CuI cluster formation, reminiscent of that
      for inorganic complexes with organothiolate ligands, is largely avoided in
      biology but is used by proteins that store copper in the cytosol of prokaryotes
      and eukaryotes, where this reactivity is also key to toxicity.

PMID- 28504852
TI  - Highly Ordered Self-Assembly of Native Proteins into 1D, 2D, and 3D Structures
      Modulated by the Tether Length of Assembly-Inducing Ligands.
AB  - In nature, proteins self-assemble into various structures with different
      dimensions. To construct these nanostructures in laboratories, normally proteins
      with different symmetries are selected. However, most of these approaches are
      engineering-intensive and highly dependent on the accuracy of the protein design.
      Herein, we report that a simple native protein LecA assembles into one
      dimensional nanoribbons and nanowires, two-dimensional nanosheets, and three
      dimensional layered structures controlled mainly by small-molecule assembly
      inducing ligands RnG (n=1, 2, 3, 4, 5) with varying numbers of ethylene oxide
      repeating units. To understand the formation mechanism of the different
      morphologies controlled by the small-molecule structure, molecular simulations
      were performed from microscopic and mesoscopic view, which presented a clear
      relationship between the molecular structure of the ligands and the assembled
      patterns. These results introduce an easy strategy to control the assembly
      structure and dimension, which could shed light on controlled protein assembly.

PMID- 28504853
TI  - Deriving ICD-11 personality disorder domains from dsm-5 traits: initial attempt
      to harmonize two diagnostic systems.
AB  - OBJECTIVE: The personality disorder domains proposed for the ICD-11 comprise
      Negative Affectivity, Detachment, Dissociality, Disinhibition, and Anankastia,
      which are reasonably concordant with the higher-order trait domains in the
      Alternative DSM-5 Model for Personality Disorders. METHOD: We examined (i)
      whether designated DSM-5 trait facets can be used to describe the proposed ICD-11
      trait domains, and (ii) how these ICD-11 trait features are hierarchically
      organized. A mixed Danish derivation sample (N = 1541) of 615 psychiatric out
      patients and 925 community participants along with a US replication sample (N =
      637) completed the Personality Inventory for DSM-5 (PID-5). Sixteen PID-5 traits
      were designated to cover features of the ICD-11 trait domains. RESULTS:
      Exploratory structural equation modeling (ESEM) analyzes showed that the
      designated traits were meaningfully organized in the proposed ICD-11 five-domain
      structure as well as other recognizable higher-order models of personality and
      psychopathology. Model fits revealed that the five proposed ICD-11 personality
      disorder domains were satisfactorily resembled, and replicated in the independent
      US sample. CONCLUSION: The proposed ICD-11 personality disorder domains can be
      accurately described using designated traits from the DSM-5 personality trait
      system. A scoring algorithm for the ICD-11 personality disorder domains is
      provided in appendix.

PMID- 28504855
TI  - Relationships between digit ratio (2D:4D) and basketball performance in
      Australian men.
AB  - OBJECTIVE: To investigate relationships between the digit ratio (2D:4D) and
      competitive basketball performance in Australian men. METHODS: Using an
      observational cross-sectional design a total of 221 Australian basketball players
      who competed in the Olympic Games, International Basketball Federation World
      Championships/Cup, Australian National Basketball League, Central Australian
      Basketball League or socially had their 2D:4Ds measured. Analysis of variance was
      used to assess differences in mean 2D:4Ds between men playing at different
      competitive standards, with relationships between 2D:4Ds and basketball game
      related statistics assessed using Pearson's product moment correlations in men
      playing at a single competitive standard. RESULTS: There were significant
      differences between competitive standards for the left 2D:4D following Bonferroni
      correction, but not for the right 2D:4D, with basketballers who achieved higher
      competitive standards tending to have lower left 2D:4Ds. No important
      correlations between 2D:4D and basketball game-related statistics were found,
      with correlations typically negligible. CONCLUSIONS: This study indicated that
      the 2D:4D can discriminate between basketballers competing at different
      standards, but not between basketballers within a single competitive standard
      using objective game-related statistics.

PMID- 28504854
TI  - The risk of early occurrence and recurrence of hepatocellular carcinoma in
      hepatitis C-infected patients treated with direct-acting antivirals with and
      without pegylated interferon: A Belgian experience.
AB  - Recently, concerns were raised of high rates of HCC recurrence in patients
      treated with direct-acting antivirals (DAA) for hepatitis C infection. We
      investigated the HCC occurrence and recurrence rates within 6 months after
      treatment with DAA with or without pegylated interferon (PEG-IFN) in real life.
      This is a retrospective, multicenter cohort trial, executed in 15 hospitals
      distributed across Belgium. Populations were matched based on fibrosis score
      (Metavir F3-F4). Patients with a Child-Pugh score >= B were excluded. In total,
      567 patients were included, of whom 77 were treated with PEG-IFN+DAA between 2008
      and 2013 and 490 with DAA without PEG-IFN between 2013 and 2015. Patients treated
      with PEG-IFN+DAA (53+/-9y) were younger than patients treated with DAA without
      PEG-IFN (59+/-12y) (P=.001). 47% of patients treated with PEG-IFN+DAA were in the
      F4 stage vs 67% of patients treated with DAA without PEG-IFN (P=.001). Screening
      was inadequate in 20% of both patient groups (P=.664). The early occurrence rate
      of HCC was 1.7% and 1.1% in patients treated with DAA with and without PEG-IFN,
      respectively (P=.540). The early recurrence rate was 0% in patients treated with
      PEG-IFN+DAA and 15.0% in patients treated with DAA without PEG-IFN (P=.857).
      There is no difference in early occurrence of new HCC between patients treated
      with DAA with and without PEG-IFN. We did observe a high early recurrence rate of
      HCC in patients treated with DAA without PEG-IFN. However, these patients were at
      baseline more at risk for HCC. Finally, in 20%, screening for HCC was inadequate.

PMID- 28504856
TI  - Cell-free DNA copy number variations in plasma from colorectal cancer patients.
AB  - To evaluate the clinical utility of cell-free DNA (cfDNA), we performed whole
      genome sequencing to systematically examine plasma cfDNA copy number variations
      (CNVs) in a cohort of patients with colorectal cancer (CRC, n = 80), polyps (n =
      20), and healthy controls (n = 35). We initially compared cfDNA yield in 20
      paired serum-plasma samples and observed significantly higher cfDNA concentration
      in serum (median = 81.20 ng, range 7.18-500 ng.mL-1 ) than in plasma (median =
      5.09 ng, range 3.76-62.8 ng.mL-1 ) (P < 0.0001). However, tumor-derived cfDNA
      content was significantly lower in serum than in matched plasma samples tested.
      With ~10 million reads per sample, the sequencing-based copy number analysis
      showed common CNVs in multiple chromosomal regions, including amplifications on
      1q, 8q, and 5q and deletions on 1p, 4q, 8p, 17p, 18q, and 22q. Copy number
      changes were also evident in genes critical to the cell cycle, DNA repair, and
      WNT signaling pathways. To evaluate whether cumulative copy number changes were
      associated with tumor stages, we calculated plasma genomic abnormality in colon
      cancer (PGA-C) score by summing the most significant CNVs. The PGA-C score showed
      predictive performance with an area under the curve from 0.54 to 0.84 for CRC
      stages I-IV. Locus-specific copy number analysis identified nine genomic regions
      where CNVs were significantly associated with survival in stage III-IV CRC
      patients. A multivariate model using six of nine genomic regions demonstrated a
      significant association of high-risk score with shorter survival (HR = 5.33, 95%
      CI = 6.76-94.44, P < 0.0001). Our study demonstrates the importance of using
      plasma (rather than serum) to test tumor-related genomic variations. Plasma cfDNA
      based tests can capture tumor-specific genetic changes and may provide a
      measurable classifier for assessing clinical outcomes in advanced CRC patients.

PMID- 28504858
TI  - AJIPHASE(r): A Highly Efficient Synthetic Method for One-Pot Peptide Elongation
      in the Solution Phase by an Fmoc Strategy.
AB  - We previously reported an efficient peptide synthesis method, AJIPHASE(r), that
      comprises repeated reactions and isolations by precipitation. This method
      utilizes an anchor molecule with long-chain alkyl groups as a protecting group
      for the C-terminus. To further improve this method, we developed a one-pot
      synthesis of a peptide sequence wherein the synthetic intermediates were isolated
      by solvent extraction instead of precipitation. A branched-chain anchor molecule
      was used in the new process, significantly enhancing the solubility of long
      peptides and the operational efficiency compared with the previous method, which
      employed precipitation for isolation and a straight-chain aliphatic group.
      Another prerequisite for this solvent-extraction-based strategy was the use of
      thiomalic acid and DBU for Fmoc deprotection, which facilitates the removal of
      byproducts, such as the fulvene adduct.

PMID- 28504857
TI  - Hysteroscopic resection of a uterine caesarean scar defect (niche) in women with
      postmenstrual spotting: a randomised controlled trial.
AB  - OBJECTIVE: To compare the effectiveness of a hysteroscopic niche resection versus
      no treatment in women with postmenstrual spotting and a uterine caesarean scar
      defect. DESIGN: Multicentre randomised controlled trial. SETTING: Eleven
      hospitals collaborating in a consortium for women's health research in the
      Netherlands. POPULATION: Women reporting postmenstrual spotting after a caesarean
      section who had a niche with a residual myometrium of >=3 mm, measured during
      sonohysterography. METHODS: Women were randomly allocated to hysteroscopic niche
      resection or expectant management for 6 months. MAIN OUTCOME MEASURES: The
      primary outcome was the number of days of postmenstrual spotting 6 months after
      randomisation. Secondary outcomes were spotting at the end of menstruation,
      intermenstrual spotting, dysuria, sonographic niche measurements, surgical
      parameters, quality of life, women's satisfaction, sexual function, and
      additional therapy. Outcomes were measured at 3 months and, except for niche
      measurements, also at 6 months after randomisation. RESULTS: We randomised 52
      women to hysteroscopic niche resection and 51 women to expectant management. The
      median number of days of postmenstrual spotting at baseline was 8 days in both
      groups. At 6 months after randomisation, the median number of days of
      postmenstrual spotting was 4 days (interquartile range, IQR 2-7 days) in the
      intervention group and 7 days (IQR 3-10 days) in the control group (P = 0.04); on
      a scale of 0-10, discomfort as a result of spotting had a median score of 2 (IQR
      0-7) in the intervention group, compared with 7 (IQR 0-8) in the control group (P
      = 0.02). CONCLUSIONS: In women with a niche with a residual myometrium of >=3 mm,
      hysteroscopic niche resection reduced postmenstrual spotting and spotting-related
      discomfort. TWEETABLE ABSTRACT: A hysteroscopic niche resection is an effective
      treatment to reduce niche-related spotting.

PMID- 28504859
TI  - Anxiety: There is an app for that. A systematic review of anxiety apps.
AB  - BACKGROUND: Smartphones and mobile devices have become ubiquitous, and with the
      rapid advance of technology, the number of health applications (apps) that are
      available for consumers on these devices is constantly growing. In particular,
      there has been a recent proliferation of anxiety apps. However, there has been no
      review of the quality or content of these anxiety apps and little is known about
      their purpose, the features they contain, and their empirical support. The goal
      of this systematic review was to assess the commercially available anxiety apps.
      METHODS: A list of anxiety apps was collected in January 2017, using the Power
      Search function of iTunes and Google Play. Of 5,078 identified apps, 52 met our
      inclusion criteria (i.e., being defined as an anxiety/worry relief app, and
      offering psychological techniques aimed primarily at reducing anxiety) and were
      further reviewed. RESULTS: The majority (67.3%) of the currently available
      anxiety apps were found to lack the involvement of health care professionals in
      their development, and very few (3.8%) of them have been rigorously tested.
      CONCLUSIONS: At the moment, although anxiety apps have the potential to enhance
      access to mental health care, there is a marked discrepancy between the wealth of
      commercially available apps, and the paucity of data regarding their efficacy and
      effectiveness. Although the great promise of apps is their ability to increasing
      access to evidence-based mental health, the field is not quite there yet and the
      full potential of apps for treating anxiety has yet to be exploited.

PMID- 28504862
TI  - Polyadenine-Modulated DNA Conformation Monitored by Surface-Enhanced Raman
      Scattering (SERS) on Multibranched Gold Nanoparticles and Its Sensing
      Application.
AB  - This work proposes a facile way to modulate the conformation of DNA from the "Lie
      Down" to the "Stand-Up" conformation on the surface of multibranched gold
      nanoparticles (AuNPs). This is realized by regulating the length of polyadenine
      (polyA) linked to the DNA sequence and/or the hybridization of this sequence with
      the target DNA, and can be monitored by the Raman signal owing to the excellent
      performance of multibranched AuNPs (AuNSs) as a surface-enhanced Raman scattering
      (SERS) substrate and the distance change between the Raman reporter and the
      substrate. The probable mechanism, which depends on the repulsion of polyA from
      the sequence and the tip assembly, has also been probed through theoretical
      simulation using the finite difference time domain method. By virtue of this
      strategy, a conformation-transformation-based DNA@AuNS sensor is constructed for
      the identification of a specific oligonucleotide, which has been used for the
      detection of DNA sequences associated with Severe Acute Respiratory Syndrome
      (SARS). This strategy leads to a novel sensing platform with good extendibility
      for DNA analysis, and provides a powerful protocol for facilitating the cognition
      of DNA conformation on metal surfaces.

PMID- 28504860
TI  - Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for
      Treatment of Aplastic Anemia: A Multicenter Phase II Trial.
AB  - We conducted a phase II, noncomparative, multicenter study to assess the efficacy
      and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs)
      expanded in vitro for patients with aplastic anemia (AA) refractory to
      immunosuppressive therapy. Seventy-four patients from seven centers received
      allogeneic BM-MSCs at a dose of 1-2 * 106 cells/kg per week for 4 weeks.
      Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first
      cells infusion. Patients with response at 1 month continued to receive four
      infusions. All patients were evaluable. The overall response rate was 28.4% (95%
      confidence interval, 19%-40%), with 6.8% complete response and 21.6% partial
      response. The median times to response of leukocytic, erythrocytic, and
      megakaryocytic linages were 19 (range, 11-29), 17 (range, 12-25), and 31 (range,
      26-84) days, respectively. After median follow-up of 17 months, overall survival
      was 87.8%. Seven patients developed transitory and mild headache and fever, but
      no other adverse events were observed. Antithymocyte globulin used in previous
      treatment and no activated infection throughout treatment were predictors for
      response. Allogeneic BM-MSCs infusion is a feasible and effective treatment
      option for refractory AA. The trial was registered at www.clinicaltrials.gov as
      NCT00195624. Stem Cells Translational Medicine 2017;6:1569-1575.

PMID- 28504861
TI  - The efficacy of benzodiazepines as acute anxiolytics in children: A meta
      analysis.
AB  - OBJECTIVE: Current practice guidelines do not recommend benzodiazepines for acute
      management of anxiety disorders in pediatric patients. However, in procedural
      settings, benzodiazepines are commonly used to relieve acute preprocedural
      stress. This meta-analysis examines the efficacy and tolerability of
      benzodiazepines as short-term anxiolytics in children. METHOD: PubMed was
      searched for randomized controlled trials assessing the efficacy of
      benzodiazepines as short-term anxiolytics in pediatric patients. Twenty-one
      trials involving 1,416 participants were included. A fixed effects model was used
      to examine the standardized mean difference of improvement in anxiety levels
      compared to control conditions. In stratified subgroup and meta-regression, the
      effect of the specific agent, dose, timing, and setting of benzodiazepine
      treatment was examined. RESULTS: A significant benefit was seen for
      benzodiazepines compared to control (standardized mean difference = 0.71 [95%
      confidence interval, 0.60-0.82], k = 24, z = 12.7, P < .001). There was also
      funnel plot asymmetry in this meta-analysis, suggesting some evidence of
      publication bias. Moderator analyses found that when benzodiazepines were used in
      dental or nonoperating room procedures, they were more effective than when they
      were used in operating room procedures (test for subgroup differences Q2 = 6.34,
      P = .04). Tolerability analysis revealed there was no significant difference in
      the risk of developing irritability or behavioral changes between benzodiazepine
      and control groups. CONCLUSIONS: Benzodiazepines are effective and well-tolerated
      when used as short-term anxiolytics in procedural settings for pediatric
      patients. Further research is needed to determine whether benzodiazepines are
      effective in pediatric anxiety disorders.

PMID- 28504863
TI  - Diagnostic accuracy of polymerase chain reaction for intrapartum detection of
      group B streptococcus colonization.
AB  - INTRODUCTION: Many pregnant women are treated with antibiotics during labor to
      prevent transmission of group B streptococcus (GBS, Streptococcus agalactiae) to
      their baby during passage of the birth canal, and so reduce the risk of serious
      infection of the newborn. Methods for intrapartum testing for GBS have been
      introduced to select women to whom intrapartum antibiotic prophylaxis should be
      offered. For such an intrapartum test to be useful in clinical practice, it has
      to be specific as well as sensitive. The aim of the present study is to evaluate
      the accuracy of the polymerase chain reaction (PCR) assay compared with an
      optimized culture method for GBS. MATERIAL AND METHODS: In the period from 12 May
      2015 to 18 December 2015 we collected rectovaginal swabs from 106 women in the
      labor ward presenting in labor between gestational week 35+0 and 36+6 or
      presenting with prelabor/preterm prelabor rupture of membranes (PROM/PPROM) for >
      14 h after gestational week 34+0 . We performed GBS culture (reference standard)
      and a molecular GBS test (Xpert GBS, Cepheid Ltd., Sunnyvale, CA, USA). RESULTS:
      Based on intrapartum culture, 23.6% (25/106) were colonized with GBS. Intrapartum
      PCR showed a colonization rate of 25.7% (27/105). The sensitivity of the test was
      100% (86.28-100%). The specificity of the test was 97.5% (91.26-99.70%). The
      positive predictive value was 92.6%. In one case, we had no result with PCR
      testing, giving an invalid test rate of < 1%. CONCLUSION: The PCR test has
      sufficient accuracy to direct intrapartum antibiotic prophylaxis for GBS
      transmission during delivery.

PMID- 28504864
TI  - Nitrated Fatty Acids Modulate the Physical Properties of Model Membranes and the
      Structure of Transmembrane Proteins.
AB  - Nitrated fatty acids (NO2 -FAs) act as anti-inflammatory signal mediators, albeit
      the molecular mechanisms behind NO2 -FAs' influence on diverse metabolic and
      signaling pathways in inflamed tissues are essentially elusive. Here, we combine
      fluorescence measurements with surface-specific sum frequency generation
      vibrational spectroscopy and coarse-grained computer simulations to demonstrate
      that NO2 -FAs alter lipid organization by accumulation at the membrane-water
      interface. As the function of membrane proteins strongly depends on both, protein
      structure as well as membrane properties, we consecutively follow the structural
      dynamics of an integral membrane protein in presence of NO2 -FAs. Based on our
      results, we suggest a molecular mechanism of the NO2 -FA in vivo activity: Driven
      by the NO2 -FA-induced lipid layer reorganization, the structure and function of
      membrane-associated (signaling) proteins is indirectly affected.

PMID- 28504865
TI  - Real-time crystallographic studies of the adenine riboswitch using an X-ray free
      electron laser.
AB  - Structures of the four reaction states of the adenine riboswitch aptamer domain,
      including a transient intermediate state were solved by serial femtosecond
      crystallography. The structures not only demonstrate the use of X-ray free
      electron lasers for RNA crystallography but have also proven that transient
      states can be determined in real time by mix-and-inject crystallography. These
      results illustrate the structural basis for the ligand-induced conformational
      changes associated with the molecular 'switch'.

PMID- 28504866
TI  - A short report on current fertility preservation strategies for boys.
AB  - BACKGROUND: Advances in cancer treatment have led to improved long-term survival
      after childhood cancer, but often at a price of impaired future fertility.
      Fertility preservation (FP) in male children and early adolescents poses unique
      challenges as efficacy is unproven. OBJECTIVES: To describe characteristics of
      testicular tissue cryopreservation (TTCP) specimens taken from paediatric and
      adolescent patients, stratified by age, and prior chemotherapy, if any, and to
      demonstrate evidence for germ cells. MATERIALS AND METHODS: Retrospective review
      of gonadal biopsies and clinical records of patients consented into the Royal
      Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into
      blocks, with one section sent for histopathology prior to cryopreservation. In
      boys >=12 years where spermatogenesis could be expected, a portion of tissue was
      disaggregated completely to look for mature sperm and if found, additional tissue
      was dissected and the resulting suspension frozen. RESULTS: Testicular tissue
      cryopreservation specimens in 44 males (0.3-16.8 years) provided an average of
      7.8 slices per patient. All the specimens were taken at the same time as another
      necessary surgical procedure, under one general anaesthesic. There was only one
      complication of scrotal wound dehiscence. Seven of the forty-four (15.9%)
      patients had chemotherapy prior to testicular biopsy, while the rest were
      chemotherapy naive. Five of these were prepubertal, and two were pubertal
      patients. Eleven subjects had tissue dissected with mature sperm found in eight.
      Of these eight patients where sperm were found, all were pubertal with testicular
      size of more than 10 mL and showing histological evidence of spermatogenesis. No
      histologic specimen demonstrated any malignant cells. CONCLUSIONS: Testicular
      tissue cryopreservation can be performed in young patients without delay,
      preferably prior to cancer treatment. As testicular tissue contains germ cells
      from which haploid spermatozoa are ultimately derived, future technologies may
      allow their utilization for fertility in humans. This may be the only hope for
      biological offspring in some patients undergoing fertility compromising
      treatment. Retrieval of mature sperm from some pubertal patients, however, offers
      realistic hope to these patients of future fertility.

PMID- 28504867
TI  - The PTPN13 Y2081D (T>G) (rs989902) polymorphism is associated with an increased
      risk of sporadic colorectal cancer.
AB  - AIM: Colorectal cancer (CRC) is one of the most common cancers worldwide and,
      although the majority of cases are sporadic, its development and progression
      depends on a range of factors: environmental, genetic and epigenetic. A variety
      of genetic pathways have been described as being crucial in CRC, including
      protein tyrosine phosphatases (PTPs). PTPN13 (also called FAP-1) is a non
      receptor PTP and interacts with a number of important components of growth and
      apoptosis pathways. It is also involved in the inhibition of Fas-induced
      apoptosis. METHOD: The single nucleotide polymorphism genotype at Y2081D (T>G)
      (rs989902) of PTPN13 exon 39 was determined in DNA extracted from blood samples
      from 174 sporadic CRC patients and 176 healthy individuals. Also, a meta-analysis
      was performed based on three articles accessed via the PubMed and ResearchGate
      databases. RESULTS: The risk of CRC was 2.087 times greater for patients with the
      GG genotype than for those with the TT genotype (P = 0.0475). In the meta
      analysis, a significantly increased risk of cancer associated with the G allele
      was observed in the squamous cell carcinoma of the head and neck subgroup (TT vs
      GG+GT, OR 1.23, 95% CI [1.02, 1.47], P = 0.0258), and a significantly decreased
      risk in the breast cancer subgroup (TT vs GG+GT, OR 0.63, 95% CI [0.41, 0.96], P
      = 0.0334) and in the CRC subgroup (GT+TT vs GG, OR 0.51, 95% CI [0.41, 0.95], P =
      0.0333). CONCLUSION: PTPN13 rs989902 is significantly associated with the risk of
      CRC in the Polish population. Given that this report provides the first evidence
      of an association of PTPN13 rs989902 with the risk of CRC in a Caucasian
      population, further large scale studies are necessary to confirm this finding.

PMID- 28504868
TI  - Recognizing Latinos' range of skin pigment and phototypes to enhance skin cancer
      prevention.
AB  - Latinos in the United States may have the mistaken assumption that their natural
      pigmentation protects them from developing skin cancer that, effectively, serves
      as a barrier to Latinos receiving education in primary and secondary prevention
      of skin cancer. Latino adults of Mexican or Puerto Rican heritage attending
      community health fairs in the greater Chicago area responded to a culturally
      informed and sensitive measure for sunburn and tan, which was previously adapted
      to capture skin irritation with tenderness from the sun occurring in darker skin
      types (n = 350). By self-reported responses and spectrophotometry assessment of
      constitutive pigmentation, adapted Fitzpatrick skin types (FST) ranged from skin
      type I-IV in the Mexican American participants and from II to V in the Puerto
      Rican participants. The objectively measured proportion of adapted FST II skin
      type was greater than commonly perceived and demonstrated that many Latinos do
      indeed have sun-sensitive skin.

PMID- 28504869
TI  - Kidney outcomes in patients with liver cirrhosis and chronic kidney disease
      receiving an orthotopic liver transplant alone.
AB  - Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney
      disease (CKD) is controversial. We report 14 liver cirrhotic patients who had
      persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40
      mL/min/1.73 m2 for >=3 months and underwent either liver transplant alone (LTA;
      n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients
      with LTA compared with SLKT had lower serum creatinine (2.5+/-0.73 vs 4.6+/-0.52
      mg/dL, P=.001), higher MDRD-6 e-GFR (21.0+/-7.2 vs 10.3+/-2.0 mL/min/1.73 m2 ,
      P=.002), higher 24-hour urine creatinine clearance (34.2+/-8.8 vs 18.0+/-2.2
      mL/min, P=.002), lower proteinuria (133.2+/-117.7 vs 663+/-268.2 mg/24 h,
      P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA,
      the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1
      month (49.8+/-8.4), 3 months (49.6+/-8.7), 6 months (49.8+/-8.1), 12 months
      (47.6+/-9.2), 24 months (47.9+/-9.1), and 36 months (45.1+/-7.3) significantly
      higher compared to pre-LTA e-GFR (P<=.005 at all time points). One patient
      developed end-stage renal disease 9 years post-LTA and another patient expired 7
      years post-LTA. The low e-GFR alone in the absence of other markers or risk
      factors of CKD should not be an absolute criterion for SLKT in patients with
      liver cirrhosis.

PMID- 28504870
TI  - A critical evaluation of the current "p-value controversy".
AB  - This article has been triggered by the initiative launched in March 2016 by the
      Board of Directors of the American Statistical Association (ASA) to counteract
      the current p-value focus of statistical research practices that allegedly "have
      contributed to a reproducibility crisis in science." It is pointed out that in
      the very wide field of statistics applied to medicine, many of the problems
      raised in the ASA statement are not as severe as in the areas the authors may
      have primarily in mind, although several of them are well-known experts in
      biostatistics and epidemiology. This is mainly due to the fact that a large
      proportion of medical research falls under the realm of a well developed body of
      regulatory rules banning the most frequently occurring misuses of p-values.
      Furthermore, it is argued that reducing the statistical hypotheses tests nowadays
      available to the class of procedures based on p-values calculated under a
      traditional one-point null hypothesis amounts to ignoring important developments
      having taken place and going on within the statistical sciences. Although
      hypotheses testing is still an indispensable part of the statistical methodology
      required in medical and other areas of empirical research, there is a large
      repertoire of methods based on different paradigms of inference that provide
      ample options for supplementing and enhancing the methods of data analysis blamed
      in the ASA statement for causing a crisis.

PMID- 28504872
TI  - Comparing student and staff perceptions of the "Educational Climate" in Spanish
      Dental Schools using the Dundee Ready Education Environment Measure.
AB  - OBJECTIVE: To compare the perceptions of students and teachers of the
      "Educational Climate" (EC) in Spanish public dental schools. METHODS: A group of
      1064 students and 354 teachers from six Spanish public dental schools responded
      to the DREEM questionnaire. This has 50 items grouped into five subscales:
      perception of learning (Learning); perception of teachers (Teachers); academic
      self-perceptions (Academic); perception of the atmosphere in the faculty
      (Atmosphere); and social self-perceptions (Social). The DREEM scale provides
      results for each item, each subscale and the overall EC. RESULTS: The EC scores
      were 123.2 (61.6%) for the students and 134.1 (67.0%) for the teachers (P<.001).
      The scores of the students and teachers for the subscales were, respectively:
      27.9 (58.1%) and 30.2 (63.0 %) for Learning (P<.001); 26.8 (60.9%) and 32.6
      (74.1%) for Teachers (P<.001); 20.7 (64.7%) and 20.5 (64.0%) for Academic
      (P=.333); 29.9 (62.3%) and 33.7 (70.3%) for Atmosphere (P<.001); and 17.9 (64.0%)
      and 16.9 (60.5%) for Social (P<.001). The students identified six problematic
      items (12.0 %) compared to only two (4.0 %) highlighted by the teachers.
      CONCLUSION: The students and teachers considered the EC to be "more positive than
      negative" in Spanish public dental schools; and the different subscales to be
      "positive and acceptable." The teachers did, however, evaluate the EC, and
      specifically the learning-teaching process, more positively than their students,
      identifying fewer problematic educational aspects. Both groups agreed on the need
      to: improve support systems for students who suffer from stress and reduce
      teaching based on "factual learning."

PMID- 28504871
TI  - Pollination and breeding system of the enigmatic South African parasitic plant
      Mystropetalon thomii (Mystropetalaceae): rodents welcome, but not needed.
AB  - Unrelated plants adapted to particular pollinator types tend to exhibit
      convergent evolution in floral traits. However, inferences about likely
      pollinators from 'pollination syndromes' can be problematic due to trait overlap
      among some syndromes and unusual floral architecture in some lineages. An example
      is the rare South African parasitic plant Mystropetalon thomii
      (Mystropetalaceae), which has highly unusual brush-like inflorescences that
      exhibit features of both bird and rodent pollination syndromes. We used camera
      traps to record flower visitors, quantified floral spectral reflectance and
      nectar and scent production, experimentally determined self-compatibility and
      breeding system, and studied pollen dispersal using fluorescent dyes. The dark
      red inflorescences are usually monoecious, with female flowers maturing before
      male flowers, but some inflorescences are purely female (gynoecious).
      Inflorescences were visited intensively by several rodent species that carried
      large pollen loads, while visits by birds were extremely rare. Rodents prefer
      male- over female-phase inflorescences, likely because of the male flowers'
      higher nectar and scent production. The floral scent contains several compounds
      known to attract rodents. Despite the obvious pollen transfer by rodents, we
      found that flowers on both monoecious and gynoecious inflorescences readily set
      seed in the absence of rodents and even when all flower visitors are excluded.
      Our findings suggest that seed production occurs at least partially through
      apomixis and that M. thomii is not ecologically dependent on its rodent
      pollinators. Our study adds another species and family to the growing list of
      rodent-pollinated plants, thus contributing to our understanding of the floral
      traits associated with pollination by non-flying mammals.

PMID- 28504873
TI  - Controlling the Regioselectivity of Baeyer-Villiger Monooxygenases by Mutation of
      Active-Site Residues.
AB  - Baeyer-Villiger monooxygenase (BVMO)-mediated regiodivergent conversions of
      asymmetric ketones can lead to the formation of "normal" or "abnormal" lactones.
      In a previous study, we were able to change the regioselectivity of a BVMO by
      mutation of the active-site residues to smaller amino acids, which thus created
      more space. In this study, we demonstrate that this method can also be used for
      other BVMO/substrate combinations. We investigated the regioselectivity of 2-oxo
      Delta3 -4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase from Pseudomonas
      putida (OTEMO) for cis-bicyclo[3.2.0]hept-2-en-6-one (1) and trans-dihydrocarvone
      (2), and we were able to switch the regioselectivity of this enzyme for one of
      the substrate enantiomers. The OTEMO wild-type enzyme converted (-)-1 into an
      equal (50:50) mixture of the normal and abnormal products. The F255A/F443V
      variant produced 90 % of the normal product, whereas the W501V variant formed up
      to 98 % of the abnormal product. OTEMO F255A exclusively produced the normal
      lactone from (+)-2, whereas the wild-type enzyme was selective for the production
      of the abnormal product. The positions of these amino acids were equivalent to
      those mutated in the cyclohexanone monooxygenases from Arthrobacter sp. and
      Acinetobacter sp. (CHMOArthro and CHMOAcineto ) to switch their regioselectivity
      towards (+)-2, which suggests that there are hot spots in the active site of
      BVMOs that can be targeted with the aim to change the regioselectivity.

PMID- 28504875
TI  - Selection of Natural Peptide Ligands for Copper-Catalyzed Azide-Alkyne
      Cycloaddition Catalysis.
AB  - The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a powerful
      tool for making connections in both organic reactions and biological systems.
      However, the use of this ligation process in living cells is limited by the
      toxicity associated with unbound copper ions. As an initial attempt to create
      peptide-based accelerating ligands capable of cellular expression, we performed
      synthesis and selection for such species on solid-phase synthesis beads bearing
      both candidate ligand and alkyne substrate. A simple histidine-containing motif
      (HXXH) was identified, and found after solution-phase optimization to produce
      single-turnover systems showing moderate rate acceleration over the ligand-free
      reaction. CuAAC reaction rates and yields for different alkynes were found to
      respond to the peptide ligands, demonstrating a substrate scope beyond what was
      used for the selection steps, but also illustrating the potential difficulty in
      evolving a general CuAAC catalyst.

PMID- 28504876
TI  - Whispering Gallery Mode Laser from Carbon Dot-NaCl Hybrid Crystals.
AB  - Carbon dot (CD)-NaCl hybrid crystals are obtained by incorporating the CDs into
      NaCl matrix through a simple process. The embedded CDs have added the
      luminescence centers into NaCl, and as a result, the hybrid crystals present the
      fluorescence centered at 510 nm under the illumination of 365 nm light.
      Meanwhile, the phosphorescence with an average lifetime of 314 ms is achieved
      after the 365 nm light was turned off. Furthermore, optical gain and lasing
      phenomenon has been observed from hybrid crystals. When the pump power is low, a
      weak spontaneous emission can be observed from the hybrid crystal, whereas the
      lasing action was observed under high pump power. The lasing threshold is found
      to be 0.08 mW and corresponding Q factor is calculated to be 447. The tiny cubic
      crystal in hybrid crystals offers the whispering gallery mode (WGM) resonant
      cavity for lasing emission. That has provided a new approach for realizing lasing
      materials.

PMID- 28504877
TI  - Illuminating Superoxide Anion and pH Enhancements in Apoptosis of Breast Cancer
      Cells Induced by Mitochondrial Hyperfusion Using a New Two-Photon Fluorescence
      Probe.
AB  - Mitochondrial morphology regulated by fusion and fission processes determines
      mitochondrial function and cell fate. Some studies showed hyperfused mitochondria
      could induce apoptosis in cancer cells, but the relevant molecular mechanisms
      remain elusive. Superoxide (O2*-) and pH play vital roles in mitochondrial
      dysfunction and apoptosis. Therefore, it is worthwhile to explore if there is an
      intimate relationship between mitochondrial hyperfusion and simultaneous changes
      in O2*- and pH levels, which will be helpful to uncover relevant detailed
      mechanism. For this purpose, we have developed a new reversible two-photon
      fluorescent probe (CFT) to simultaneously monitor O2*- and pH in 4T1 cells and
      mice using dual-color imaging. With the assistance of probe, we found that
      inhibition of Dynamin-related protein 1 (Drp1) could transduce a signal through
      mitochondrial complexes I and II to enhance the O2*- and pH levels and eventually
      induced mitohyperfusion and apoptosis in breast cancer cells. Together, these
      data indicate that CFT provides a robust tool for unveiling the roles of O2*- and
      pH in signals associated with mitochondrial dysfunction in cells and in vivo.

PMID- 28504874
TI  - Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules
      and Supporting Mesh: Six-Year Clinical Follow-Up Results.
AB  - Several alternative techniques exist to reconstruct skull defects. The
      complication rate of the cranioplasty procedure is high and the search for
      optimal materials and techniques continues. To report long-term results of
      patients who have received a cranioplasty using autologous adipose-derived stem
      cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between
      10/2008 and 3/2010, five cranioplasties were performed (four females, one male;
      average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable
      meshes. The average defect size was 8.1 * 6.7 cm2 . Patients were followed both
      clinically and radiologically. The initial results were promising, with no
      serious complications. Nevertheless, in the long-term follow-up, three of the
      five patients were re-operated due to graft related problems. Two patients showed
      marked resorption of the graft, which led to revision surgery. One patient
      developed a late infection (7.3 years post-operative) that required revision
      surgery and removal of the graft. One patient had a successfully ossified graft,
      but was re-operated due to recurrence of the meningioma 2.2 years post
      operatively. One patient had an uneventful clinical follow-up, and the cosmetic
      result is satisfactory, even though skull x-rays show hypodensity in the borders
      of the graft. Albeit no serious adverse events occurred, the 6-year follow-up
      results of the five cases are unsatisfactory. The clinical results are not
      superior to results achieved by conventional cranial repair methods. The use of
      stem cells in combination with betaTCP granules and supporting meshes in cranial
      defect reconstruction need to be studied further before continuing with clinical
      trials. Stem Cells Translational Medicine 2017;6:1576-1582.

PMID- 28504878
TI  - Raspberry-like Nanostructured Silicon Composite Anode for High-Performance
      Lithium-Ion Batteries.
AB  - Adjusting the particle size and nanostructure or applying carbon materials as the
      coating layers is a promising method to hold the volume expansion of Si for its
      practical application in lithium-ion batteries (LIBs). Herein, the mild carbon
      coating combined with a molten salt reduction is precisely designed to synthesize
      raspberry-like hollow silicon spheres coated with carbon shells (HSi@C) as the
      anode materials for LIBs. The HSi@C exhibits a remarkable electrochemical
      performance; a high reversible specific capacity of 886.2 mAh g-1 at a current
      density of 0.5 A g-1 after 200 cycles is achieved. Moreover, even after 500
      cycles at a current density of 2.0 A g-1, a stable capacity of 516.7 mAh g-1
      still can be obtained.

PMID- 28504880
TI  - Navigating Past a Fork in the Road: Carbocation-pi Interactions Can Manipulate
      Dynamic Behavior of Reactions Facing Post-Transition-State Bifurcations.
AB  - Dynamics calculations are described for carbocation rearrangements involving
      product-forming pathways with post-transition-state bifurcations. We show that
      noncovalent interactions with associated benzene rings (a simple model of
      aromatic amino acid side chains) can switch inherent dynamical tendencies for
      competing modes of disrotation, establishing that meaningful changes in
      dynamically controlled product selectivity can be achieved with few weak
      noncovalent interactions.

PMID- 28504881
TI  - Compartmentalization Technologies via Self-Assembly and Cross-Linking of
      Amphiphilic Random Block Copolymers in Water.
AB  - Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random
      block copolymers in water afforded an approach to tailor-make well-defined
      compartments and domains in single polymer chains and nanoaggregates. For a
      double compartment single-chain polymer, an amphiphilic random block copolymer
      bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl,
      and olefin pendants was synthesized by living radical polymerization (LRP) and
      postfunctionalization; the dodecyl and benzyl units were incorporated into the
      different block segments, whereas PEG pendants were statistically attached along
      a chain. The copolymer self-folded via the orthogonal self-assembly of
      hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular
      cross-linking, to form a single-chain polymer carrying double yet distinct
      hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine
      terminal served as a globular macroinitiator for LRP to provide an amphiphilic
      tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic
      polymer tail; the tadpole thus self-assembled into multicompartment aggregates in
      water.

PMID- 28504879
TI  - Antitubercular Activity of Mycelium-Associated Ganoderma Lanostanoids.
AB  - In a continuation of our research into antitubercular lanostane triterpenoids
      from submerged cultures of Ganoderma species, three strains, Ganoderma orbiforme
      BCC 22325, Ganoderma sp. BCC 60695, and Ganoderma australe BCC 22314, have been
      investigated. Fourteen new lanostane triterpenoids, together with 35 known
      compounds, were isolated. Antitubercular activities of these mycelium-associated
      Ganoderma lanostanoids against Mycobacterium tuberculosis H37Ra were evaluated.
      Taken together with the assay data of previously isolated compounds, structure
      activity relationships of the antitubercular activity are proposed. Most
      importantly, 3beta- and 15alpha-acetoxy groups were shown to be critical for
      antimycobacterial activity. The most potent compound was (24E)-3beta,15alpha
      diacetoxylanosta-7,9(11),24-trien-26-oic acid (35).

PMID- 28504882
TI  - Visible-Light-Induced Tandem Radical Addition-Cyclization of Alkenyl Aldehydes
      Leading to Indanones and Related Compounds.
AB  - Herein we describe a novel, visible light-induced tandem radical addition
      cyclization of alkenyl aldehydes with alpha-bromocarbonyl compounds. A set of
      cyclic ketones, including indanones, cyclopentenones, 3,4-dihydronaphthalen-1(2H)
      ones, and chroman-4-ones, are synthesized at room temperature with high
      efficiency and good functional group compatibility. It represents the first
      report on the catalytic 1,2-acylalkylation of unactivated alkenes.

PMID- 28504883
TI  - Synergetic Effect of Monomer Functional Group Coordination in Catalytic Insertion
      Polymerization.
AB  - PhS- and PhNH-functionalized dienes are copolymerized efficiently with butadiene
      to stereoregular copolymers by [(mesitylene)Ni(allyl)][BArF4] (Ni-1). Overall
      polymerization rates and comonomer incorporations depend strongly on the linker
      length between the diene moiety and functional group, in, e.g., PhS-(CH2)xC(?CH2)
      CH?CH2 (PhS-x-BD, x = 3-7), in particular for certain linker lengths high
      comonomer reactivity ratios stand out. This effect is related to a favorable
      binding of the comonomer to the active site comprising coordination of its
      functional group, which significantly enhances comonomer incorporation in the
      growing polymer chain.

PMID- 28504884
TI  - d-alpha-Tocopheryl Succinate/Phosphatidyl Ethanolamine Conjugated Amphiphilic
      Polymer-Based Nanomicellar System for the Efficient Delivery of Curcumin and To
      Overcome Multiple Drug Resistance in Cancer.
AB  - Nanomedicines have emerged as a promising treatment strategy for cancer. Multiple
      drug resistance due to overexpression of various drug efflux transporters and
      upregulation of apoptotic inhibitory pathways in cancer cells are major barriers
      that limit the success of chemotherapy. Here, we developed a d-alpha-tocopherol
      (alpha-TOS)/lipid-based copolymeric nanomicellar system (VPM) by conjugating
      phosphatidyl ethanolamine (PE) and alpha-TOS with poly(ethylene glycol) (PEG) via
      an amino acid linkage. The synthesized polymers were characterized by Fourier
      transform IR, gas-phase chromatography, and 1H and 13C NMR spectroscopy. VPM
      exhibited mean hydrodynamic diameter of 141.0 +/- 0.94 nm with low critical
      micelles concentrations (CMC) of 15 MUM compared to plain PEG-PE micelles (PPM)
      with size of 23.9 +/- 0.34 nm and CMC 20 MUM. The bigger hydrophobic compartment
      in VPM resulted in improved loading of a potent chemotherapeutic drug, curcumin
      (Cur), and increased encapsulation efficiency (EE) (% drug loading 98.3 +/- 1.92,
      and 85.3 +/- 3.29; EE 14.8 +/- 0.16 and 12.8 +/- 0.09 for VPM and PPM,
      respectively). Curcumin loaded Vitamin E based micelles exhibited higher
      cytotoxicity compared to Curcumin loaded PEG-PE micelles in tested cancer cell
      lines. C-VPM demonstrated ~3.2 and ~2.7-fold higher ability to reverse multiple
      drug resistance compared to PPM and verapamil (concentration used 30 MUM),
      respectively. In the in vivo study by using B16F10 implanted C57Bl6/J mice, C-VPM
      reduced the tumor volume and weight more efficiently than C-PPM by inducing
      apoptosis as analyzed by TUNEL assay on tumor cryosections. The newly developed
      polymeric micelles, VPM with improved drug loadability and ability to reverse the
      drug resistance could successfully be utilized as a nanocarrier system for
      hydrophobic chemotherapeutic agents for the treatment of drug-resistant solid
      tumors.

PMID- 28504885
TI  - Uranyl Coordination by the 14-Membered Macrocycle
      Dibenzotetramethyltetraaza[14]annulene.
AB  - Reaction of [UO2(N(SiMe3)2)2(THF)2] with 1 equiv of
      dibenzotetramethyltetraaza[14]annulene (tmtaaH2) affords the uranyl complex
      [UO2(tmtaaH)(N(SiMe3)2) (THF)] (1) (THF = tetrahydrofuran) as red blocks in 83%
      yield. Similarly, thermolysis of a mixture of [UO2(N(SiMe3)2)2(THF)2] and 2 equiv
      of tmtaaH2 affords [UO2(tmtaaH)2] (2), which can be isolated as red-orange
      crystals in 67% yield after workup. Both 1 and 2 were fully characterized,
      including analysis by X-ray crystallography. The tmtaaH ligands in 1 and 2 are
      only coordinated to the uranium center via one beta-diketiminate fragment, while
      the protonated beta-diketimine portion of the ligand remains uncoordinated.
      Reaction of [UO2(N(SiMe3)2)2(THF)2] with 1 equiv of Li2(tmtaa) in C6H6 results in
      the formation of [Li(THF)]2[UO2(N(SiMe3)2)2(tmtaa)] (3), which can be isolated in
      55% yield as a red-brown crystalline solid. The tmtaa ligand in complex 3
      supports a dative interaction between an oxo ligand in the uranyl fragment and a
      lithium cation, suggesting that tmtaa could be a useful ligand for developing the
      oxo ligand functionalization chemistry of the uranyl ion.

PMID- 28504886
TI  - Nanoparticle-Delivered 2-PAM for Rat Brain Protection against Paraoxon Central
      Toxicity.
AB  - Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to
      target the blood-brain barrier (BBB) for drug delivery to the central nervous
      system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime
      chloride (2-PAM), in SLNs appears to be a suitable strategy for protection
      against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2
      PAM-loaded SLNs were developed for brain targeting and delivery via intravenous
      (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency
      (~90%) and loading capacity (maximum 30.8 +/- 1%). Drug-loaded particles had a
      mean hydrodynamic diameter close to 100 nm and high negative zeta potential (-54
      to -15 mV). These properties contribute to improve long-term stability of 2-PAM
      SLNs when stored both at room temperature (22  degrees C) and at 4  degrees C, as
      well as to longer circulation time in the bloodstream compared to free 2-PAM.
      Paraoxon-poisoned rats (2 * LD50) were treated with 2-PAM-loaded SLNs at a dose
      of 2-PAM of 5 mg/kg. 2-PAM-SLNs reactivated 15% of brain AChE activity. Our
      results confirm the potential use of SLNs loaded with positively charged oximes
      as a medical countermeasure both for protection against OPs poisoning and for
      postexposure treatment.

PMID- 28504887
TI  - CO2-Controlled One-Pot Synthesis of AB, ABA Block, and Statistical Terpolymers
      from beta-Butyrolactone, Epoxides, and CO2.
AB  - Terpolymerizations of (rac)-beta-butyrolactone (BBL), cyclohexene oxide (CHO),
      and carbon dioxide were realized in one-pot reactions utilizing a Lewis acid
      BDICF3-Zn-N(SiMe3)2 (1) catalyst. The type of polymerization can be regulated and
      switched between ring-opening polymerization (ROP) of BBL and CHO/CO2
      copolymerization by the presence of CO2 in the reaction mixture. Applying 3 bar
      CO2 to the three-component system leads to similar reaction rates for
      copolymerization and ROP and therefore to a terpolymer with a statistical
      composition, whereas 40 bar CO2 affords exclusive copolymerization of CHO/CO2.
      Two-dimensional NMR spectroscopy and polarimetry provided a deeper understanding
      of the underlying mechanism. Furthermore, copolymerization of cyclopentene oxide
      (CPO) and CO2 was performed, resulting in the highest reported TOF of 3200 h-1
      together with 99% polycarbonate selectivity. Terpolymerizations of CPO/CO2 and
      BBL were successfully conducted using the established reaction pathways.

PMID- 28504888
TI  - Cytotoxic Bagremycins from Mangrove-Derived Streptomyces sp. Q22.
AB  - New bagremycins C-E (3-5) and bagrelactone A (6), together with known bagremycins
      A (1) and B (2), 4-hydroxystyrene (7), and 4-hydroxystyrene 4-O-alpha-d
      galactopyranoside (8), were isolated from a mangrove-derived actinomycete,
      Streptomyces sp. Q22. Structures of these new compounds were elucidated based on
      their NMR and HRESIMS spectroscopic data as well as chemical degradation.
      Bagremycin C (3) is a unique analogue with an N-acetyl-(S)-cysteine moiety, while
      bagrelactone A (6) represents the first example of this type of bagremycin
      derived macrolide. Bagremycin C (3) was active against four glioma cell lines,
      with IC50 values in the range from 2.2 to 6.4 MUM, induced apoptosis in human
      glioma U87MG cells in a dose- and time-dependent manner, and arrested the U87MG
      cell cycle at the G0/G1 phase.

PMID- 28504889
TI  - Genetic Characterization of vanA-Enterococcus faecium Isolates from Wild Red
      Legged Partridges in Portugal.
AB  - Vancomycin-resistant enterococci (VRE) have been detected in wild animals
      representing a public health concern. The red-legged partridge (Alectoris rufa)
      is a common game bird and its meat is consumed in several countries, including
      Portugal. Three hundred five fecal samples of red-legged partridge from the north
      of Portugal were screened for VRE. Samples were cultured on Slanetz-Bartley agar
      supplemented with vancomycin (4 mg/L) and six vanA-Enterococcus faecium were
      recovered. Isolates were tested for antibiotic resistance and virulence genes.
      Multilocus sequence typing (MLST) was performed to study the genotypic diversity
      of vanA-containing E. faecium. The six isolates showed erythromycin resistance
      and harbored the erm(B) gene and the four that were tetracycline resistant showed
      the tet(M) gene. The C-terminal region of the pbp5 gene of the ampicillin
      resistant isolates (minimal inhibitory concentration range of 256 MUg/ml) was
      sequenced. Two different pbp5 alleles were detected when considering the changes
      of amino acid in 461-629 region. All isolates harbored the esp gene, whereas hyl,
      together with the esp gene, was detected in five isolates. MLST analysis grouped
      the isolates as ST448 (n = 1), ST139 (n = 1), and ST18 (n = 4). Our findings show
      that the red-legged partridges could be a reservoir of antimicrobial resistance
      genes and may contribute to the dissemination and transference of the resistance
      genes to other animals and humans.

PMID- 28504890
TI  - A brief perspective of drug resistance toward EGFR inhibitors: the crystal
      structures of EGFRs and their variants.
AB  - The EGFR is one of the most popular targets for anticancer therapies and many
      drugs, such as erlotinib and gefitinib, have got enormous success in clinical
      treatments of cancer in past decade. However, the efficacy of these agents is
      often limited because of the quick emergence of drug resistance. Fundamental
      structure researches of EGFR in recent years have generally elucidated the
      mechanism of drug resistance. In this review, based on systematic resolution of
      full structures of EGFR and their variants via single crystal x-ray
      crystallography, the working and drug resistance mechanism of EGFR-targeted drugs
      are fully illustrated. Moreover, new strategies for avoiding EGFR drug resistance
      in cancer treatments are also discussed.

PMID- 28504891
TI  - Intelligence and Fitness: The Mediating Role of Educational Level.
AB  - The evolutionary status of intelligence is not clear: It is positively related to
      various indicators of fitness but negatively to reproductive success as the most
      important fitness marker. In the present research, we explored the links between
      intelligence and three fitness indicators: number of children (short-term
      reproductive success), number of grandchildren (long-term reproductive success),
      and age at first birth. Participants were individuals in a postreproductive stage
      ( N = 191; mean age = 66.5 years). Intelligence had a positive correlation with
      short-term reproductive success and age at first birth but a negative correlation
      with long-term reproductive success. Participants' education turned out to be a
      significant mediator of the link between intelligence and criterion measures. The
      results showed that intelligence can elevate short-term reproductive success.
      Furthermore, individuals with higher intellectual abilities tended to delay
      reproduction, which negatively affected their long-term reproductive success.
      Education was revealed as a very important resource which affects the link
      between cognitive abilities and fitness, thus proving its evolutionary role in
      contemporary populations.

PMID- 28504892
TI  - Palliative Care Interventions before Left Ventricular Assist Device Implantation
      in Both Bridge to Transplant and Destination Therapy.
AB  - BACKGROUND: The optimal level of palliative care (PC) involvement in left
      ventricular assist device (LVAD) therapy has yet to be determined. OBJECTIVE:
      Describe the feasibility of PC intervention to elucidate patients' goals and
      values in LVAD therapy in both destination therapy (DT) and bridge to transplant
      (BTT). DESIGN: Single center, prospective, single-arm study. SETTING/SUBJECTS:
      All patients who received mandatory PC consultation, using a semistructured
      script, before LVAD implantation (PreVAD evaluation). MEASUREMENTS: We evaluated
      the feasibility of PreVAD evaluation and family awareness by analyzing responses
      and compared it between DT and BTT. We examined the association between
      withdrawal of LVAD therapy and family awareness in death cases. RESULTS: Between
      January 2014 and September 2016, 112 patients (DT, 75; BTT, 37) underwent PreVAD
      evaluation. All patients could express what makes their life meaningful, and 101
      (92.0%) could discuss possible complications. Seventy-nine patients (70.5%) could
      articulate their unacceptable health state. There was no difference between both
      groups. Family awareness increased significantly from 33.0% to 58.0% after PreVAD
      evaluation (p < 0.01). Five LVADs were deactivated among the 12 death cases, and
      they were all from the family-aware group (71.2% vs. 0%, p = 0.027). CONCLUSIONS:
      Integrated PC intervention was feasible for both BTT and DT patients. Such an
      intervention may increase family awareness of the patient's unique concerns and
      may have an impact on decision making at the end of life.

PMID- 28504893
TI  - Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's
      disease.
AB  - Accumulating evidence indicates a solid relationship between several enzymes and
      Alzheimer's disease. Cholinesterases and monoamine oxidases are closely
      associated with the disease symptomatology and progression and have been tackled
      simultaneously using several multifunctional ligands. This design strategy offers
      great chances to alter the course of Alzheimer's disease, in addition to
      alleviation of the symptoms. More than 15 years of research has led to the
      identification of various dual cholinesterase/monoamine oxidase inhibitors, while
      some showing positive outcomes in clinical trials, thus giving rise to additional
      research efforts in the field. The aim of this review is to provide an update on
      the novel dual inhibitors identified recently and to shed light on their
      therapeutic potential.

PMID- 28504894
TI  - Preventing Burdensome Transitions of Nursing Home Residents with Advanced
      Dementia: It's More than Advance Directives.
AB  - BACKGROUND: Although a palliative approach to care is recommended for people with
      advanced dementia, many nursing home (NH) residents with dementia experience
      burdensome interventions such as hospital transfers at the end of life.
      OBJECTIVE: The goal of this study was to examine how decisions to transfer NH
      residents with advanced dementia are made, from the perspective of NH nurses and
      physicians. METHODS: A qualitative, descriptive method was used. Purposive
      sampling was used to recruit 20 healthcare providers from 9 NHs. Data collection
      included semistructured, open-ended interviews. RESULTS: Decision making
      regarding hospital transfer comprised two phases. Phase one, laying the
      groundwork, was influenced by the ability of the providers to effectively
      establish trust, foreshadow, and illuminate hazards of hospitalization. Phase
      two, responding to an acute event, began at the start of an acute event and ended
      when a decision was made to either treat the resident in the NH or transfer to
      the hospital. Responding to the acute event was influenced by the ability to care
      for residents in the NH, the providers' comfort with end-of-life conversations,
      and surrogates' preferences. CONCLUSIONS: Advance care planning before an acute
      event is only the first step in a process of decision making. Attention to and
      support for decision making is needed at the time of each acute event to ensure
      that goals of care are maintained.

PMID- 28504896
TI  - Pulmonary Arterial Sarcoma Presenting as Acute Pulmonary Embolism.

PMID- 28504895
TI  - Progress toward inhibitors of metallo-beta-lactamases.
AB  - The global overuse of antibiotics has led to the emergence of drug-resistant
      pathogenic bacteria. Bacteria can combat beta-lactams by expressing beta
      lactamases. Inhibitors of one class of beta-lactamase, the serine-beta
      lactamases, are used clinically to prevent degradation of beta-lactam
      antibiotics. However, a second class of beta-lactamase, the metallo-beta
      lactamases (MBLs), function by a different mechanism to serine-beta-lactamases
      and no inhibitors of MBLs have progressed to be used in the clinic. Bacteria that
      express MBLs are an increasingly important threat to human health. This review
      outlines various approaches taken to discover MBL inhibitors, with an emphasis on
      the different chemical classes of inhibitors. Recent progress, particularly new
      screening methods and the rational design of potent MBL inhibitors are discussed.

PMID- 28504899
TI  - Metabolic Diversity and Novelties in the Oomycetes.
AB  - The eukaryotic microbes called oomycetes include many important saprophytes and
      pathogens, with the latter exhibiting necrotrophy, biotrophy, or obligate
      biotrophy. Understanding oomycete metabolism is fundamental to understanding
      these lifestyles. Genome mining and biochemical studies have shown that
      oomycetes, which belong to the kingdom Stramenopila, secrete suites of
      carbohydrate- and protein-degrading enzymes adapted to their environmental niches
      and produce unusual lipids and energy storage compounds. Despite having limited
      secondary metabolism, many oomycetes make chemicals for communicating within
      their species or with their hosts. Horizontal and endosymbiotic gene transfer
      events have diversified oomycete metabolism, resulting in biochemical pathways
      that often depart from standard textbook descriptions by amalgamating enzymes
      from multiple sources. Gene fusions and duplications have further shaped the
      composition and expression of the enzymes. Current research is helping us learn
      how oomycetes interact with host and environment, understand eukaryotic diversity
      and evolution, and identify targets for drugs and crop protection chemicals.

PMID- 28504900
TI  - Corrigendum: Costs of Selective Attention: When Children Notice What Adults Miss.

PMID- 28504897
TI  - Clonal Complexes and Antimicrobial Susceptibility Profiles of Staphylococcus
      pseudintermedius Isolates from Dogs in the United States.
AB  - Staphylococcus pseudintermedius is the primary cause of canine pyoderma and has
      been associated with diseases in other animals, including human beings. A high
      prevalence of methicillin and multidrug resistance has been reported in this
      bacterium in some geographic regions of the United States. Multilocus sequence
      type (MLST) 68 was implicated, initially, as the major clonal genotype based on a
      limited number of samples. The objectives of this study were to determine the
      population genetics of S. pseudintermedius isolated from a cross-section of the
      United States using a seven-locus multilocus sequence typing method, to identify
      clonal complexes (CCs), and to correlate sequence types with antimicrobial
      susceptibility profiles. A total of 190 S. pseudintermedius with 86 different
      MLSTs were detected and the constituents of three major CCs of methicillin
      resistant S. pseudintermedius (MRSP), CC68, CC71, and CC84, were identified.
      Different patterns of resistance were associated with each CC. CC71 from the
      United States had notable differences with CC71 studied on other continents with
      chloramphenicol, tetracycline, and trimethoprim/sulfamethoxazole resistance. Some
      isolates with resistance to the broadest range of drugs tested, including that to
      chloramphenicol, had STs unrelated to the major CCs, suggesting the potential for
      the emergence of new clonal populations of MRSP that are resistant to most
      therapeutically useful antimicrobials.

PMID- 28504898
TI  - Dissociable Contributions of Imagination and Willpower to the Malleability of
      Human Patience.
AB  - The ability to exercise patience is important for human functioning. Although it
      is known that patience can be promoted by using top-down control, or willpower,
      to override impatient impulses, patience is also malleable-in particular,
      susceptible to framing effects-in ways that are difficult to explain using
      willpower alone. So far, the mechanisms underlying framing effects on patience
      have been elusive. We investigated the role of imagination in these effects. In a
      behavioral experiment (Experiment 1), a classic framing manipulation (sequence
      framing) increased self-reported and independently coded imagination during
      intertemporal choice. In an investigation of neural responses during decision
      making (Experiment 2), sequence framing increased the extent to which patience
      was related to activation in brain regions associated with imagination, relative
      to activation in regions associated with willpower, and increased functional
      connectivity of brain regions associated with imagination, but not willpower,
      relative to regions associated with valuation. Our results suggest that sequence
      framing can increase the role of imagination in decision making without
      increasing the exertion of willpower.

PMID- 28504901
TI  - Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation,
      and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered
      Patients With Cancer and Chemotherapy-Induced Anemia.
AB  - PURPOSE: The US Food and Drug Administration (FDA) has approved epoetin and
      darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and
      darbepoetin dosing schedules were three times per week and weekly, respectively,
      although off-label, less frequent scheduling was common. In 2004, 2007, and 2008,
      a US Food and Drug Administration Advisory Committees warned of risks associated
      with erythropoiesis-stimulating agents. During this period, lawsuits alleging
      illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion
      in fines and settlements and one criminal conviction. No prior study, to our
      knowledge, has reported on the use of darbepoetin versus epoetin for CIA.
      METHODS: We evaluated the dosing, utilization, and costs of erythropoiesis
      stimulating agents among 3,761 South Carolina Medicaid patients with CIA.
      RESULTS: Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10%
      and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per
      administration epoetin and darbepoetin doses were 40,983 IU and 191 ug,
      respectively, in 2003 and 47,753 IU and 369 ug, respectively, in 2010. Mean
      monthly patient costs for epoetin and darbepoetin were $1,030 and $981,
      respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use
      decreased steadily between 2002 and 2010; darbepoetin use increased steadily
      between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing
      of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and
      monthly per-patient epoetin costs decreased 3% while the per-patients costs of
      darbepoetin increased 30% between 2003 and 2010. CONCLUSION: To our knowledge,
      our findings are the first data reporting on epoetin versus darbepoetin use for
      CIA and support recently concluded lawsuits involving allegations of illegal
      marketing practices of the manufacturer of darbepoetin.

PMID- 28504902
TI  - Reply to C.D. Woodrell et al.

PMID- 28504903
TI  - Hepatocellular Carcinoma: A Wrinkle in the Emerging Palliative Care/Oncology
      Paradigm.

PMID- 28504904
TI  - Application of Panel-Based Tests for Inherited Risk of Cancer.
AB  - Next-generation or massively parallel sequencing has transformed the landscape of
      genetic testing for cancer susceptibility. Panel-based genetic tests evaluate
      multiple genes simultaneously and rapidly. Because these tests are frequently
      offered in clinical settings, understanding their clinical validity and utility
      is critical. When evaluating the inherited risk of breast and ovarian cancers,
      panel-based tests provide incremental benefit compared with BRCA1/2 genetic
      testing. For inherited risk of other cancers, such as colon cancer and
      pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based
      testing are higher; in fact, simultaneous evaluation of multiple genes has been
      the historical standard for these diseases. Evaluating inherited risk with panel
      based testing has recently entered clinical practice for prostate and pancreatic
      cancers, with potential therapeutic implications. The resulting variants of
      uncertain significance and mutations with unclear actionability pose challenges
      to service providers and patients, underscoring the importance of genetic
      counseling and data-sharing initiatives. This review explores the evolving
      merits, challenges, and nuances of panel-based testing for cancer susceptibility.

PMID- 28504905
TI  - Antibiotics for Sepsis: Does Each Hour Really Count, or Is It Incestuous
      Amplification?

PMID- 28504906
TI  - The Epigenetics of Intrauterine Smoke Exposure: Can Maternal Vitamin C
      Supplementation Prevent Neonatal Respiratory Disease?

PMID- 28504907
TI  - Early Lung Function Decline in Cystic Fibrosis. Can Registry Data Explain
      Divergent Phenotypes?

PMID- 28504908
TI  - Mammea longifolia Planch. and Triana Fruit Extract Induces Cell Death in the
      Human Colon Cancer Cell Line, SW480, via Mitochondria-Related Apoptosis and
      Activation of p53.
AB  - The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia)
      fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer
      cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3
      (4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate
      dehydrogenase assays, respectively. One hundred MUg/mL of the extract killed
      ~82.4% of the cells; however, 2% of the death was related to necrosis. The
      morphological changes in M. longifolia-stimulated SW480 cells were observed
      directly by light microscopy. DNA fragmentation assay was employed to analyze the
      apoptosis induction. M. longifolia-treated SW480 cells promoted the expression of
      Bax, Bad, cleaved-poly-ADP-ribose polymerase (PARP), and p53 proteins and
      decreased the protein expression of pro-caspases Bcl-2 and Bcl-XL. The ratios of
      Bax/Bcl-2 and cleaved-PARP/PARP, predictive markers of apoptotic stimuli in
      cancer, increased and may play an important role in regulating the progression of
      apoptosis. The results suggested that M. longifolia induces cell death via
      mitochondrial-related apoptosis in SW480 cells.

PMID- 28504909
TI  - Ethanol Extract of Brassica rapa ssp. pekinensis Suppresses Tumor Necrosis Factor
      alpha-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells.
AB  - Brassica rapa L. ssp. pekinensis, commonly known as Chinese cabbage, is a
      cruciferous vegetable traditionally consumed in east Asia. Although its habitual
      consumption could account for the low incidence of chronic vascular inflammation,
      the therapeutic and protective potential of phytochemicals derived from Chinese
      cabbage has been poorly studied. In this study, we identified the phenolic
      compounds, kaempferol and quercetin, from the ethanol extract of Chinese cabbage
      (EtCC). We show for the first time that EtCC contains effective phytochemicals
      that suppress tumor necrosis factor (TNF)-alpha-induced inflammatory response in
      human umbilical vein endothelial cells. The EtCC inhibited TNF-alpha-induced
      monocyte adhesion to endothelial cells in a dose-dependent manner. The
      antiadhesive activity of EtCC directly correlated with downregulation of
      expression and transcription of vascular cell adhesion molecule-1 (VCAM-1). It
      was caused by an Nrf-2-dependent mechanism, leading to activation of antioxidant
      responsive element-driven promoter. Taken together, these results suggest that
      EtCC inhibits the expression of TNF-alpha-induced adhesion molecules through the
      indirect transcriptional modulation of VCAM-1 in endothelial cells. In
      conclusion, regular consumption of vegetables containing dietary phytochemicals
      might be a potential therapeutic strategy to protect against various stresses, to
      prevent several pathological conditions, and to treat chronic vascular
      inflammation, such as atherosclerosis.

PMID- 28504910
TI  - Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose
      Intolerance in High-Fat Diet-Induced Obese Mice.
AB  - Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver
      disease (NAFLD), are primary risk factors for life-threatening conditions such as
      diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical
      tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and
      anticancer effects. Fermentation can further improve the safety and nutritional
      value of certain foods. We investigated the efficacy of fermented M. oleifera
      extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic
      lipid accumulation and investigated the underlying mechanisms by analyzing
      expression of proteins and genes involved in glucose and lipid regulation.
      C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with
      distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for
      10 weeks. Although body weights were similar among HFD-fed treatment groups,
      liver weight was decreased, and glucose tolerance test (GTT) results improved in
      the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also
      lower in the FM group, and expressions of genes involved in liver lipid
      metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER)
      stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased
      by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in
      the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may
      decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER
      stress, oxidative stress, and inflammation.

PMID- 28504911
TI  - The Value of Sharing Information: A Neural Account of Information Transmission.
AB  - Humans routinely share information with one another. What drives this behavior?
      We used neuroimaging to test an account of information selection and sharing that
      emphasizes inherent reward in self-reflection and connecting with other people.
      Participants underwent functional MRI while they considered personally reading
      and sharing New York Times articles. Activity in neural regions involved in
      positive valuation, self-related processing, and taking the perspective of others
      was significantly associated with decisions to select and share articles, and
      scaled with preferences to do so. Activity in all three sets of regions was
      greater when participants considered sharing articles with other people rather
      than selecting articles to read themselves. The findings suggest that people may
      consider value not only to themselves but also to others even when selecting news
      articles to consume personally. Further, sharing heightens activity in these
      pathways, in line with our proposal that humans derive value from self-reflection
      and connecting to others via sharing.

PMID- 28504913
TI  - Neurodegenerative drug discovery: building on the past, looking to the future.

PMID- 28504914
TI  - G-protein-coupled receptor-based drugs rediscovered.

PMID- 28504912
TI  - Synthesis and biological assessment of racemic benzochromenopyrimidinetriones as
      promising agents for Alzheimer's disease therapy.
AB  - AIM: Due to the complex nature of Alzheimer's disease, there is a renewed search
      for multitarget directed drugs. RESULTS: This paper describes the synthesis and
      in vitro biological evaluation of six racemic 13-aryl-2,3,4,13-tetrahydro-1H,12H
      benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-triones (1a-6a), and six
      racemic 15-aryl-8,9,10,11,12,15-hexahydro-14H-benzo[6',7']chromeno[2',3:4,5] pyr
      imido [1,2-a]azepine-5,14,16-triones (1b-6b), showing antioxidant and
      cholinesterase inhibitory capacity. Among these compounds, 13-phenyl-2,3,4,13
      tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-trione
      (1a) is a nonhepatotoxic at 300 MUmol/l dose concentration, and a selective
      EeAChE inhibitor showing good antioxidant power. CONCLUSION: A new family of
      racemic benzochromenopyrimidinetriones has been investigated for their potential
      use in the treatment of Alzheimer's disease.

PMID- 28504915
TI  - Prevalence of Os Styloideum in National Hockey League Players.
AB  - BACKGROUND: Os styloideum describes an accessory carpal ossicle between the
      trapezoid, the capitate, and the second and third metacarpals. Injuries to this
      tissue have been described as part of the carpal boss syndrome. While the
      etiology of os styloideum remains uncertain, it may represent a physiologic
      response to altered loading forces in the wrist, similar to the development of
      cam-type deformity in the hips of ice hockey players or the Bennett lesion in the
      shoulders of baseball pitchers. HYPOTHESIS: Professional hockey players will have
      a higher prevalence of os styloideum compared with the general population. STUDY
      DESIGN: Case series. LEVEL OF EVIDENCE: Level 4. METHODS: A retrospective review
      of 16 professional hockey players from 4 different National Hockey League (NHL)
      teams who underwent unilateral imaging of the wrist was performed. Seventeen
      wrists were reviewed for the presence of os styloideum. RESULTS: Thirteen of 16
      players (81%) had an os styloideum, representing an increased prevalence compared
      with the general population. Previous clinical and cadaveric studies estimated a
      general prevalence of up to 19% ( P < 0.001). For the 10 players who had their
      leading wrist scanned, 9 had an os styloideum (90%). Ten of 11 (91%) players
      demonstrated a bone marrow edema pattern within the metacarpal and the os
      styloideum on magnetic resonance imaging. There was no significant association
      between the presence of an os styloideum and the player's position, leading
      wrist, or years in the league. CONCLUSION: There appears to be an increased
      prevalence of os styloideum among NHL players, and team physicians should
      consider this finding while formulating a differential diagnosis for dorsal wrist
      pain. CLINICAL RELEVANCE: This study identified NHL players as having an
      increased prevalence of os styloideum compared with the general population. By
      doing so, these findings represent an opportunity to enhance our understanding of
      the etiology, clinical significance, and treatment of os styloideum.

PMID- 28504916
TI  - Contribution of Type II Topoisomerase Mutations to Fluoroquinolone Resistance in
      Enterococcus faecium from Japanese Clinical Setting.
AB  - High-level fluoroquinolone resistance is conferred by the mutation of conserved
      serine and acidic amino acids in the quinolone resistance-determining region
      (QRDR) of the A subunits of the type II topoisomerases, DNA gyrase (GyrA) and
      topoisomerase IV (ParC). In Japan, fluoroquinolone-resistant Enterococcus faecium
      continues to emerge in clinical settings. We analyzed 131 Japanese E. faecium
      clinical isolates for susceptibility to levofloxacin (LVFX), and QRDR mutational
      status. The bacterial collection had a high percentage of resistance (79%) and
      showed elevated drug minimal inhibitory concentrations (MICs). Eighty-three
      isolates had single or combined mutations in gyrA and/or parC; all were resistant
      to LVFX. A strong correlation was evident between log-transformed MICs and the
      total number of QRDR mutations (r = 0.7899), confirming the involvement of QRDR
      mutations in drug resistance, as previously described. Three-dimensional modeling
      indicated that the amino acid change(s) in QRDR could disrupt the interaction
      between the enzymes and drugs: the most common cause of quinolone resistance.
      Interestingly, eight isolates had a single mutation on gyrA and exhibited
      significantly reduced susceptibility. These data imply that either DNA gyrase or
      topoisomerase IV can be the primary target of fluoroquinolones, although
      topoisomerase IV is commonly thought to be the primary target in gram-positive
      bacteria.

PMID- 28504917
TI  - Modulating 5-HT4 and 5-HT6 receptors in Alzheimer's disease treatment.
AB  - Alzheimer's disease (AD) is the most common form of dementia affecting millions
      of patients worldwide which can only be treated with symptomatic drugs. Among the
      numbers of biological targets which are today explored in order to prevent or
      limit the progression of AD, the modulation of 5-HT6R and 5-HT4R appeared to be
      promising. This modulation has been proved to enhance the cognition in AD through
      modulation of the neurotransmitter system but could also be beneficial in order
      to limit the amyloid pathology. This review will describe recent advances in the
      understanding of this modulation as well as the medicinal chemistry of 5-HT6R or
      5-HT4R ligands from synthesis to ongoing clinical trials.

PMID- 28504918
TI  - Sheep Placenta Cotyledons: A Noninvasive Source of Ovine Mesenchymal Stem Cells.
AB  - Sheep are one of the most frequently used large animal models in stem cell
      research. However, minimal invasive or noninvasive sources of mesenchymal stem
      cells (MSCs) in sheep are scarce. In the light of the principles of the 3Rs
      (reduce, refine, replace), it would therefore be desirable to identify a
      minimally invasive or noninvasive ovine MSC source. In humans, the chorionic
      villi of the placenta, which can be noninvasively harvested as part of the
      afterbirth, have been identified as a rich source of MSCs. Therefore, in the
      present study, ovine placenta cotyledons, which have similar function and
      structure to human chorionic villi, were tested for their potential use as a
      noninvasive source of ovine MSCs. Through mincing of the placental cotyledons,
      collagenase digestion, and Ficoll density gradient centrifugation, combined with
      plastic adherence selection, MSCs were successfully isolated. Their
      morphological, immunophenotypical, and cellular growth characteristics, as well
      as their proliferation, differentiation, and migration potential, were evaluated
      and compared to the currently best-researched MSC source, bone marrow-derived
      stem cells. Ovine cotyledons were shown to be a reliable, abundant source for the
      noninvasive, pain- and risk-free harvest of MSCs. The collection procedure does
      not interfere with partum or the initial bonding phase between ewes and lambs and
      is therefore exempt from ethical debate. Ovine placenta cotyledon-derived MSCs
      exhibit multipotential characteristics and can be cryopreserved for later use.

PMID- 28504919
TI  - Does Knowing Hurt? Perceiving Oneself as Overweight Predicts Future Physical
      Health and Well-Being.
AB  - Identifying oneself as being overweight may be associated with adverse health
      outcomes, yet prospective tests of this possibility are lacking. Over 7 years, we
      examined associations between perceptions of being overweight and subsequent
      health in a sample of 3,582 U.S. adults. Perceiving oneself as being overweight
      predicted longitudinal declines in subjective health ( d = -0.22, p < .001),
      increases in depressive symptoms ( d = 0.09, p < .05), and raised levels of
      physiological dysregulation ( d = 0.24, p < .001), as gauged by clinical
      indicators of cardiovascular, inflammatory, and metabolic functioning. These
      associations remained after controlling for a range of potential confounders and
      were observed irrespective of whether perceptions of being overweight were
      accurate or inaccurate. This research highlights the possibility that identifying
      oneself as overweight may act independently of body mass index to contribute to
      unhealthy profiles of physiological functioning and impaired health over time.
      These findings underscore the importance of evaluating whether weight-feedback
      interventions may have unforeseen adverse consequences.

PMID- 28504920
TI  - Silicon's Role in Abiotic and Biotic Plant Stresses.
AB  - Silicon (Si) plays a pivotal role in the nutritional status of a wide variety of
      monocot and dicot plant species and helps them, whether directly or indirectly,
      counteract abiotic and/or biotic stresses. In general, plants with a high root or
      shoot Si concentration are less prone to pest attack and exhibit enhanced
      tolerance to abiotic stresses such as drought, low temperature, or metal
      toxicity. However, the most remarkable effect of Si is the reduction in the
      intensities of a number of seedborne, soilborne, and foliar diseases in many
      economically important crops that are caused by biotrophic, hemibiotrophic, and
      necrotrophic plant pathogens. The reduction in disease symptom expression is due
      to the effect of Si on some components of host resistance, including incubation
      period, lesion size, and lesion number. The mechanical barrier formed by the
      polymerization of Si beneath the cuticle and in the cell walls was the first
      proposed hypothesis to explain how this element reduced the severity of plant
      diseases. However, new insights have revealed that many plant species supplied
      with Si have the phenylpropanoid and terpenoid pathways potentiated and have a
      faster and stronger transcription of defense genes and higher activities of
      defense enzymes. Photosynthesis and the antioxidant system are also improved for
      Si-supplied plants. Although the current understanding of how this overlooked
      element improves plant reaction against pathogen infections, pest attacks, and
      abiotic stresses has advanced, the exact mechanism(s) by which it modulates plant
      physiology through the potentiation of host defense mechanisms still needs
      further investigation at the genomic, metabolomic, and proteomic levels.

PMID- 28504922
TI  - Abstracts: International Society for Aerosols in Medicine e.V. 21st ISAM Congress
      Santa Fe, NM June 3-7, 2017.

PMID- 28504921
TI  - Plasminogen Activator Inhibitor-1 and Pericardial Fat in Individuals with Type 2
      Diabetes Mellitus.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is implicated in the
      pathophysiology of cardiovascular disease (CVD) and increased in individuals with
      type 2 diabetes mellitus (T2DM). Adipose tissue produces PAI-1, and pericardial
      fat is a CVD risk factor. We sought to determine the relationship between PAI-1
      and pericardial fat in males and females with well-controlled T2DM. METHODS: The
      study population consisted of 32 males and 19 females, aged 35-70 years with
      T2DM, without clinical evidence of CVD or other active medical problems except
      for hypertension. Subjects were studied under good cardiometabolic control. Study
      procedures included fasting blood work and cardiovascular imaging. Cardiac
      magnetic resonance imaging of the heart was used to identify and quantify
      pericardial fat from the bifurcation of the pulmonary trunk to the last slice
      containing cardiac tissue. RESULTS: PAI-1 was positively correlated with
      pericardial fat (beta = 0.72, r = 0.72, P < 0.001) as well as with homeostatic
      model assessment of insulin resistance (r = 0.31, P = 0.03) and serum
      triglycerides (r = 0.27, P = 0.05). In a multivariable regression model,
      controlling for insulin sensitivity, triglycerides, and body mass index,
      pericardial fat was independently associated with PAI-1 (beta = 0.80, P < 0.001).
      CONCLUSIONS: PAI-1 is positively associated with pericardial fat in individuals
      with T2DM.

PMID- 28504924
TI  - mRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2)
      and peroxisome proliferator-activated receptor gamma (PPARG) transcription
      factors in colorectal carcinoma.
AB  - Transcription factors are involved in cell cycle and apoptosis regulation and
      thus have a key role in the carcinogenesis of different tumors. Nuclear factor of
      activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated
      receptor gamma (PPARG) transcription factors are important in the carcinogenesis
      of colorectal cancer (CRC). In this study, we examined whether the expression of
      NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC.
      A total of 47 tumor samples and matched normal tissue margins were collected
      during surgery from patients with CRC. In addition, three CRC cell lines (HCT119,
      SW480, and HT29) and healthy cell line were used. After total RNA extraction and
      cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real
      time polymerase chain reaction. The results showed that NFATc2 is overexpressed
      in the tumor tissues compared with normal tissue margins (p <= 0.05). However,
      the mRNA expression levels of PPARG were not significantly different between the
      tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as
      an early diagnostic or predictive biomarker for CRC as well as a therapeutic
      target, providing that upcoming studies confirm these results.

PMID- 28504926
TI  - Accurate differentiation of Mycobacterium chimaera from Mycobacterium
      intracellulare by MALDI-TOF MS analysis.
AB  - PURPOSE: The increasing number of infections caused by nontuberculous
      mycobacteria (NTM) has prompted the need for rapid and precise identification
      methods of these pathogens. Several studies report the applicability of MALDI-TOF
      mass spectrometry (MS) for identification of NTM. However, some closely related
      species have very similar spectral mass fingerprints, and until recently,
      Mycobacterium chimaera and M. intracellulare could not be separated from each
      other by MALDI-TOF MS. METHODOLOGY: The conventional identification methods used
      in routine diagnostics have similar limitations. Recently, the differentiation of
      these two species within the Mycobacterium avium complex has become increasingly
      important due to reports of M. chimaera infections related to open heart surgery
      in Europe and in the USA. In this report, a method for the distinct
      differentiation of M. chimaera and M. intracellulare using a more detailed
      analysis of MALDI-TOF mass spectra is presented. KEY FINDINGS: Species-specific
      peaks could be identified and it was possible to assign all isolates (100 %) from
      reference strain collections as well as clinical isolates to the correct species.
      CONCLUSIONS: We have developed a model for the accurate identification of M.
      chimaera and M. intracellulare by MALDI-TOF MS. This approach has the potential
      for routine use in microbiology laboratories, as the model itself can be easily
      implemented into the software of the currently available systems by MALDI-TOF MS
      manufacturers.

PMID- 28504925
TI  - Comparative diagnostic test evaluation of serum procalcitonin and C-reactive
      protein in suspected bloodstream infections in children with cancer.
AB  - PURPOSE: To compute diagnostic test properties of C-reactive protein (CRP) and
      serum procalcitonin (PCT) levels in bloodstream infections in children with
      cancer and suspected sepsis, in comparison with blood culture as the gold
      standard. METHODOLOGY: Consecutive paediatric cancer patients, aged <=14 years,
      with clinically suspected bloodstream infections were evaluated with blood
      culture and assay of PCT and CRP levels. Blood culture was taken as the gold
      standard for comparison. Sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), likelihood ratio (LR) and receiver
      operating characteristic (ROC) with area under ROC curve (AUC) were calculated to
      assess the diagnostic test performance for PCT and CRP.Results/Key findings. The
      ROC curve for PCT was better than that for CRP, with an AUC of 0.751 for PCT at a
      cut-off of 2.25 ng ml-1. The AUC for CRP was 0.638 at a cut-off of 8.0 mg dl-1.
      Among the three cut-off values of PCT selected from the ROC curve applicable to
      the patients under study, the cut-off value of >=0.49 ng ml-1 had the maximum
      sensitivity of 81.4 % and an NPV of 94.67 %; >=2.25 ng ml-1 had a sensitivity and
      specificity of 65.12 and 71.6 %, respectively, and >=6.47 ng ml-1 had a maximum
      specificity of 82.10 %. For CRP, the cut-off value of >=5.3 mg dl-1 had the
      maximum sensitivity of 72.09 %; >=8.0 mg dl-1 had a sensitivity and specificity
      of 58.14 and 68.09 %, respectively, and >=8.4 mg dl-1 had the maximum specificity
      of 70.04 %. CONCLUSION: PCT is a better serological marker for excluding
      bloodstream infections than CRP. The cut-off value of 0.49 ng ml-1 with a
      negative predictive value of 94.67 % will be ideal in a clinical setting of
      immune-compromised children with suspected sepsis.

PMID- 28504927
TI  - Mechanisms of quinolone action and resistance: where do we stand?
AB  - Quinolone antibiotics represent one of the most important classes of anti
      infective agents and, although still clinically valuable, their use has been
      compromised by the increasing emergence of resistant strains, which has become a
      prevalent clinical problem. Quinolones act by inhibiting the activity of DNA
      gyrase and topoisomerase IV - two essential bacterial enzymes that modulate the
      chromosomal supercoiling required for critical nucleic acid processes. The
      acquisition of quinolone resistance is recognized to be multifactorial and
      complex. The main resistance mechanism consists of one or a combination of target
      site gene mutations that alter the drug-binding affinity of target enzymes.
      However, other mechanisms such as mutations that lead to reduced intracellular
      drug concentrations, by either decreased uptake or increased efflux, and plasmid
      encoded resistance genes producing either target protection proteins, drug
      modifying enzymes or multidrug efflux pumps are known to contribute additively to
      quinolone resistance. The understanding of these different resistance mechanisms
      has improved significantly in recent years; however, many details remain to be
      clarified and the contribution of less-studied mechanisms still needs to be
      better elucidated in order to fully understand this phenotype.

PMID- 28504930
TI  - Extracorporeal Stimulation of Sacral Nerve Roots for Observation of Pelvic
      Autonomic Nerve Integrity: Description of a Novel Methodological Setup.
AB  - INTRODUCTION: Neurophysiologic monitoring can improve autonomic nerve sparing
      during critical phases of rectal cancer surgery. OBJECTIVES: To develop a system
      for extracorporeal stimulation of sacral nerve roots. METHODS: Dedicated software
      controlled a ten-electrode stimulation array by switching between different
      electrode configurations and current levels. A built-in impedance and current
      level measurement assessed the effectiveness of current injection. Intra-anal
      surface electromyography (sEMG) informed on targeting the sacral nerve roots. All
      tests were performed on five pig specimens. RESULTS: During switching between
      electrode configurations, the system delivered 100% of the set current (25 mA, 30
      Hz, 200 MUs cathodic pulses) in 93% of 250 stimulation trains across all
      specimens. The impedance measured between single stimulation array contacts and
      corresponding anodes across all electrode configurations and specimens equaled
      3.7 +/- 2.5 kOmega. The intra-anal sEMG recorded a signal amplitude increase as
      previously observed in the literature. When the stimulation amplitude was tested
      in the range from 1 to 21 mA using the interconnected contacts of the stimulation
      array and the intra-anal anode, the impedance remained below 250 Omega and the
      system delivered 100% of the set current in all cases. Intra-anal sEMG showed an
      amplitude increase for current levels exceeding 6 mA. CONCLUSION: The system
      delivered stable electric current, which was proved by built-in impedance and
      current level measurements. Intra-anal sEMG confirmed the ability to target the
      branches of the autonomous nervous system originating from the sacral nerve
      roots. SIGNIFICANCE: Stimulation outside of the operative field during rectal
      cancer surgery is feasible and may improve the practicality of pelvic
      intraoperative neuromonitoring.

PMID- 28504931
TI  - Robust Real-Time Musculoskeletal Modeling Driven by Electromyograms.
AB  - OBJECTIVE: Current clinical biomechanics involves lengthy data acquisition and
      time-consuming offline analyses with biomechanical models not operating in real
      time for man-machine interfacing. We developed a method that enables online
      analysis of neuromusculoskeletal function in vivo in the intact human. METHODS:
      We used electromyography (EMG)-driven musculoskeletal modeling to simulate all
      transformations from muscle excitation onset (EMGs) to mechanical moment
      production around multiple lower-limb degrees of freedom (DOFs). We developed a
      calibration algorithm that enables adjusting musculoskeletal model parameters
      specifically to an individual's anthropometry and force-generating capacity. We
      incorporated the modeling paradigm into a computationally efficient, generic
      framework that can be interfaced in real-time with any movement data collection
      system. RESULTS: The framework demonstrated the ability of computing forces in 13
      lower-limb muscle-tendon units and resulting moments about three joint DOFs
      simultaneously in real-time. Remarkably, it was capable of extrapolating beyond
      calibration conditions, i.e., predicting accurate joint moments during six unseen
      tasks and one unseen DOF. CONCLUSION: The proposed framework can dramatically
      reduce evaluation latency in current clinical biomechanics and open up new
      avenues for establishing prompt and personalized treatments, as well as for
      establishing natural interfaces between patients and rehabilitation systems.
      SIGNIFICANCE: The integration of EMG with numerical modeling will enable
      simulating realistic neuromuscular strategies in conditions including
      muscular/orthopedic deficit, which could not be robustly simulated via pure
      modeling formulations. This will enable translation to clinical settings and
      development of healthcare technologies including real-time bio-feedback of
      internal mechanical forces and direct patient-machine interfacing.

PMID- 28504932
TI  - Generalizing Pooling Functions in CNNs: Mixed, Gated, and Tree.
AB  - In this paper, we seek to improve deep neural networks by generalizing the
      pooling operations that play a central role in the current architectures. We
      pursue a careful exploration of approaches to allow pooling to learn and to adapt
      to complex and variable patterns. The two primary directions lie in: (1) learning
      a pooling function via (two strategies of) combining of max and average pooling,
      and (2) learning a pooling function in the form of a tree-structured fusion of
      pooling filters that are themselves learned. In our experiments every generalized
      pooling operation we explore improves performance when used in place of average
      or max pooling. We experimentally demonstrate that the proposed pooling
      operations provide a boost in invariance properties relative to conventional
      pooling and set the state of the art on several widely adopted benchmark
      datasets. These benefits come with only a light increase in computational
      overhead during training (ranging from additional 5 to 15 percent in time
      complexity) and a very modest increase in the number of model parameters (e.g.,
      additional 1, 9, and 27 parameters for mixed, gated, and 2-level tree pooling
      operators, respectively). To gain more insights about our proposed pooling
      methods, we also visualize the learned pooling masks and the embeddings of the
      internal feature responses for different pooling operations. Our proposed pooling
      operations are easy to implement and can be applied within various deep neural
      network architectures.

PMID- 28504933
TI  - A Novel Linelet-Based Representation for Line Segment Detection.
AB  - This paper proposes a method for line segment detection in digital images. We
      propose a novel linelet-based representation to model intrinsic properties of
      line segments in rasterized image space. Based on this, line segment detection,
      validation, and aggregation frameworks are constructed. For a numerical
      evaluation on real images, we propose a new benchmark dataset of real images with
      annotated lines called YorkUrban-LineSegment. The results show that the proposed
      method outperforms state-of-the-art methods numerically and visually. To our best
      knowledge, this is the first report of numerical evaluation of line segment
      detection on real images.

PMID- 28504928
TI  - The murine catecholamine methyltransferase mTOMT is essential for
      mechanotransduction by cochlear hair cells.
AB  - Hair cells of the cochlea are mechanosensors for the perception of sound.
      Mutations in the LRTOMT gene, which encodes a protein with homology to the
      catecholamine methyltransferase COMT that is linked to schizophrenia, cause
      deafness. Here, we show that Tomt/Comt2, the murine ortholog of LRTOMT, has an
      unexpected function in the regulation of mechanotransduction by hair cells. The
      role of mTOMT in hair cells is independent of mTOMT methyltransferase function
      and mCOMT cannot substitute for mTOMT function. Instead, mTOMT binds to putative
      components of the mechanotransduction channel in hair cells and is essential for
      the transport of some of these components into the mechanically sensitive
      stereocilia of hair cells. Our studies thus suggest functional diversification
      between mCOMT and mTOMT, where mTOMT is critical for the assembly of the
      mechanotransduction machinery of hair cells. Defects in this process are likely
      mechanistically linked to deafness caused by mutations in LRTOMT/Tomt.

PMID- 28504929
TI  - Evolution of an intricate J-protein network driving protein disaggregation in
      eukaryotes.
AB  - Hsp70 participates in a broad spectrum of protein folding processes extending
      from nascent chain folding to protein disaggregation. This versatility in
      function is achieved through a diverse family of J-protein cochaperones that
      select substrates for Hsp70. Substrate selection is further tuned by transient
      complexation between different classes of J-proteins, which expands the range of
      protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the
      prevalence and evolutionary conservation of J-protein complexation and
      cooperation in disaggregation. We find the emergence of a eukaryote-specific
      signature for interclass complexation of canonical J-proteins. Consistently,
      complexes exist in yeast and human cells, but not in bacteria, and correlate with
      cooperative action in disaggregation in vitro. Signature alterations exclude some
      J-proteins from networking, which ensures correct J-protein pairing, functional
      network integrity and J-protein specialization. This fundamental change in J
      protein biology during the prokaryote-to-eukaryote transition allows for
      increased fine-tuning and broadening of Hsp70 function in eukaryotes.

PMID- 28504934
TI  - Vision-Based Surgical Field Defogging.
AB  - Fogged surgical field visualization that is a common and potentially harmful
      problem can lead to inappropriate device use and incorrectly targeted tissue and
      increase surgical risks in endoscopic surgery. This paper aims to remove fog or
      smoke on endoscopic video sequences to augment and maintain a direct and clear
      visualization of the operating field. A new visibility-driven fusion defogging
      framework is proposed for surgical endoscopic video processing. This framework
      first recovers the visibility and enhances the contrast of hazy images. To
      address the color infidelity problem introduced by the visibility recovery, the
      luminances of the recovered and enhanced images are fused in the gradient domain,
      and the fused luminance is reconstructed by solving the Poisson equation in the
      frequency domain. The proposed method is evaluated on clinical videos that were
      collected from prostate cancer surgery. The experimental results demonstrate that
      the proposed framework defogs endoscopic images more robustly than currently
      available methods. Additionally, our method also provides an effective way to
      improve the visual quality of medical or high-dynamic range images.

PMID- 28504935
TI  - Efficient 3-D Model-Based Reconstruction Scheme for Arbitrary Optoacoustic
      Acquisition Geometries.
AB  - Optimal optoacoustic tomographic sampling is often hindered by the frequency
      dependent directivity of ultrasound sensors, which can only be accounted for with
      an accurate 3-D model. Herein, we introduce a 3-D model-based reconstruction
      method applicable to optoacoustic imaging systems employing detection elements
      with arbitrary size and shape. The computational complexity and memory
      requirements are mitigated by introducing an efficient graphic processing unit
      (GPU)-based implementation of the iterative inversion. On-the-fly calculation of
      the entries of the model-matrix via a small look-up table avoids otherwise
      unfeasible storage of matrices typically occupying more than 300GB of memory.
      Superior imaging performance of the suggested method with respect to standard
      optoacoustic image reconstruction methods is first validated quantitatively using
      tissue-mimicking phantoms. Significant improvements in the spatial resolution,
      contrast to noise ratio and overall 3-D image quality are also reported in real
      tissues by imaging the finger of a healthy volunteer with a hand-held volumetric
      optoacoustic imaging system.

PMID- 28504936
TI  - Wave Mode Discrimination of Coded Ultrasonic Guided Waves Using Two-Dimensional
      Compressed Pulse Analysis.
AB  - Ultrasonic guided waves testing is a technique successfully used in many
      industrial scenarios worldwide. For many complex applications, the dispersive
      nature and multimode behavior of the technique still poses a challenge for
      correct defect detection capabilities. In order to improve the performance of the
      guided waves, a 2-D compressed pulse analysis is presented in this paper. This
      novel technique combines the use of pulse compression and dispersion compensation
      in order to improve the signal-to-noise ratio (SNR) and temporal-spatial
      resolution of the signals. The ability of the technique to discriminate different
      wave modes is also highlighted. In addition, an iterative algorithm is developed
      to identify the wave modes of interest using adaptive peak detection to enable
      automatic wave mode discrimination. The employed algorithm is developed in order
      to pave the way for further in situ applications. The performance of Barker-coded
      and chirp waveforms is studied in a multimodal scenario where longitudinal and
      flexural wave packets are superposed. The technique is tested in both synthetic
      and experimental conditions. The enhancements in SNR and temporal resolution are
      quantified as well as their ability to accurately calculate the propagation
      distance for different wave modes.

PMID- 28504937
TI  - Ultrasonic Fingerprint Sensor With Transmit Beamforming Based on a PMUT Array
      Bonded to CMOS Circuitry.
AB  - In this paper, we present a single-chip 65 *42 element ultrasonic pulse-echo
      fingerprint sensor with transmit (TX) beamforming based on piezoelectric
      micromachined ultrasonic transducers directly bonded to a CMOS readout
      application-specific integrated circuit (ASIC). The readout ASIC was realized in
      a standard 180-nm CMOS process with a 24-V high-voltage transistor option. Pulse
      echo measurements are performed column-by-column in sequence using either one
      column or five columns to TX the ultrasonic pulse at 20 MHz. TX beamforming is
      used to focus the ultrasonic beam at the imaging plane where the finger is
      located, increasing the ultrasonic pressure and narrowing the 3-dB beamwidth to
      [Formula: see text], a factor of 6.4 narrower than nonbeamformed measurements.
      The surface of the sensor is coated with a poly-dimethylsiloxane (PDMS) layer to
      provide good acoustic impedance matching to skin. Scanning laser Doppler
      vibrometry of the PDMS surface was used to map the ultrasonic pressure field at
      the imaging surface, demonstrating the expected increase in pressure, and
      reduction in beamwidth. Imaging experiments were conducted using both PDMS
      phantoms and real fingerprints. The average image contrast is increased by a
      factor of 1.5 when beamforming is used.

PMID- 28504938
TI  - Perceptual Real-Time 2D-to-3D Conversion Using Cue Fusion.
AB  - We propose a system to infer binocular disparity from a monocular video stream in
      real-time. Different from classic reconstruction of physical depth in computer
      vision, we compute perceptually plausible disparity, that is numerically
      inaccurate, but results in a very similar overall depth impression with plausible
      overall layout, sharp edges, fine details and agreement between luminance and
      disparity. We use several simple monocular cues to estimate disparity maps and
      confidence maps of low spatial and temporal resolution in real-time. These are
      complemented by spatially-varying, appearance-dependent and class-specific
      disparity prior maps, learned from example stereo images. Scene classification
      selects this prior at runtime. Fusion of prior and cues is done by means of
      robust MAP inference on a dense spatio-temporal conditional random field with
      high spatial and temporal resolution. Using normal distributions allows this in
      constant-time, parallel per-pixel work. We compare our approach to previous 2D-to
      3D conversion systems in terms of different metrics, as well as a user study and
      validate our notion of perceptually plausible disparity.

PMID- 28504939
TI  - Correlation-Preserving Photo Collage.
AB  - A new method is presented for producing photo collages that preserve content
      correlation of photos. We use deep learning techniques to find correlation among
      given photos to facilitate their embedding on the canvas, and develop an
      efficient combinatorial optimization technique to make correlated photos stay
      close to each other. To make efficient use of canvas space, our method first
      extracts salient regions of photos and packs only these salient regions. We allow
      the salient regions to have arbitrary shapes, therefore yielding informative, yet
      more compact collages than by other similar collage methods based on salient
      regions. We present extensive experimental results, user study results, and
      comparisons against the state-of-the-art methods to show the superiority of our
      method.

PMID- 28504940
TI  - Good Random Multi-Triangulation of Surfaces.
AB  - We introduce the Hierarchical Poisson Disk Sampling Multi-Triangulation (HPDS-MT)
      of surfaces, a novel structure that combines the power of multi-triangulation
      (MT) with the benefits of Hierarchical Poisson Disk Sampling (HPDS). MT is a
      general framework for representing surfaces through variable resolution triangle
      meshes, while HPDS is a well-spaced random distribution with blue noise
      characteristics. The distinguishing feature of the HPDS-MT is its ability to
      extract adaptive meshes whose triangles are guaranteed to have good shape
      quality. The key idea behind the HPDS-MT is a preprocessed hierarchy of points,
      which is used in the construction of a MT via incremental simplification. In
      addition to proving theoretical properties on the shape quality of the triangle
      meshes extracted by the HPDS-MT, we provide an implementation that computes the
      HPDS-MT with high accuracy. Our results confirm the theoretical guarantees and
      outperform similar methods. We also prove that the Hausdorff distance between the
      original surface and any (extracted) adaptive mesh is bounded by the sampling
      distribution of the radii of Poisson-disks over the surface. Finally, we
      illustrate the advantages of the HPDS-MT in some typical problems of geometry
      processing.

PMID- 28504941
TI  - Advanced Hierarchical Spherical Parameterizations.
AB  - Computing spherical parameterizations for genus-zero closed surfaces is a
      fundamental task for geometric processing and computer graphics. Existing methods
      usually suffer from a lack of practical robustness or poor quality. In this
      paper, we present a practically robust method to compute high-quality spherical
      parameterizations with bijection and low isometric distortion. Our method is
      based on the hierarchical scheme containing mesh decimation and parameterization
      refinement. The practical robustness of our method relies on two novel
      techniques. The first one is a flat-to-extrusive decimation strategy, which
      contains two decimation error metrics to alleviate the difficulty of further mesh
      refinement. The second is a flexible group refinement technique that consists of
      flexible vertex insertion and efficient volumetric distortion minimization to
      control the maximum distortion. We convert the task of volumetric distortion
      minimization to one of tetrahedral mesh improvement to make the vertices
      distribute uniformly for efficient refinement. Compared with state-of-the-art
      methods, our method is more practically robust and possesses better mapping
      qualities. We demonstrate the efficacy of our method in spherical
      parameterization computations on a data set containing over five thousand complex
      models.

PMID- 28504942
TI  - Interaction of Perceived Frequency and Intensity in Fingertip Electrotactile
      Stimulation: Dissimilarity Ratings and Multidimensional Scaling.
AB  - Sensations elicited by electrical stimulation of touch are multidimensional,
      varying in perceived intensity and quality in response to changes in stimulus
      current or waveform timing. This paper manipulated both current and frequency,
      while volunteer participants estimated the dissimilarity of all non-identical
      pairs of 16 stimulus conditions. Multidimensional scaling analysis revealed that
      a model having two perceptual dimensions was adequate in representing the
      electrotactile (electrocutaneous) sensations. The two dimensions were identified
      as perceptual frequency and intensity, and were strongly correlated with the two
      stimulus variables, frequency and current, although not in a 1:1 correspondence.
      Perception of frequency differences increased monotonically with stimulus
      intensity, which is consistent with other human sensory systems, such as hearing
      and vision. Our results are consistent with previously-reported research using a
      different methodology and cutaneous locus. Congruence across different methods
      and laboratories suggests similar underlying perceptual mechanisms.

PMID- 28504943
TI  - Toward Multimodal Human-Robot Interaction to Enhance Active Participation of
      Users in Gait Rehabilitation.
AB  - Robotic exoskeletons for physical rehabilitation have been utilized for
      retraining patients suffering from paraplegia and enhancing motor recovery in
      recent years. However, users are not voluntarily involved in most systems. This
      paper aims to develop a locomotion trainer with multiple gait patterns, which can
      be controlled by the active motion intention of users. A multimodal human-robot
      interaction (HRI) system is established to enhance subject's active participation
      during gait rehabilitation, which includes cognitive HRI (cHRI) and physical HRI
      (pHRI). The cHRI adopts brain-computer interface based on steady-state visual
      evoked potential. The pHRI is realized via admittance control based on
      electromyography. A central pattern generator is utilized to produce rhythmic and
      continuous lower joint trajectories, and its state variables are regulated by
      cHRI and pHRI. A custom-made leg exoskeleton prototype with the proposed
      multimodal HRI is tested on healthy subjects and stroke patients. The results
      show that voluntary and active participation can be effectively involved to
      achieve various assistive gait patterns.

PMID- 28504944
TI  - Perspective: It's All About Time.
AB  - New knowledge on multi-scale temporal dynamics linking nanobio-time series,
      seasonal changes, immune response, and gut mictobiota can milestone (neuro)
      science soon.

PMID- 28504945
TI  - A Bio-Inspired Hybrid Thermal Management Approach for 3-D Network-on-Chip
      Systems.
AB  - 3-D network-on-chip (NoC) systems are getting popular among the integrated
      circuit (IC) manufacturer because of reduced latency, heterogeneous integration
      of technologies on a single chip, high yield, and consumption of less
      interconnecting power. However, the addition of functional units in the 
      direction has resulted in higher on-chip temperature and appearance of local
      hotspots on the die. The increase in temperature degrades the performance,
      lifetime, and reliability, and increases the maintenance cost of 3-D ICs. To keep
      the heat within an acceptable limit, floorplanning is the widely accepted
      solution. Proper arrangement of functional units across different layers can lead
      to uniform thermal distribution in the chip. For systems with high density of
      elements, few hotspots cannot be eliminated in the floorplanning approach. To
      overcome, liquid microchannel cooling technology has emerged as an efficient and
      scalable solution for 3-D NoC. In this paper, we propose a novel hybrid algorithm
      combining both floorplanning, and liquid microchannel placement to alleviate the
      hotspots in high-density systems. A mathematical model is proposed to deal with
      heat transfer due to diffusion and convention. The proposed approach is
      independent of topology. Three different topologies: 3-D stacked homogeneous mesh
      architecture, 3-D stacked heterogeneous mesh architecture, and 3-D stacked
      ciliated mesh architecture are considered to check the effectiveness of the
      proposed algorithm in hotspot reduction. A thermal comparison is made with and
      without the proposed thermal management approach for the above architectures
      considered. It is observed that there is a significant reduction in on-chip
      temperature when the proposed thermal management approach is applied.

PMID- 28504946
TI  - Essential Protein Detection by Random Walk on Weighted Protein-Protein
      Interaction Networks.
AB  - Essential proteins are critical to the development and survival of cells.
      Identification of essential proteins is helpful for understanding the minimal set
      of required genes in a living cell and for designing new drugs. To detect
      essential proteins, various computational methods have been proposed based on
      protein-protein interaction (PPI) networks. However, protein interaction data
      obtained by highthroughput experiments usually contain high false positives,
      which negatively impacts the accuracy of essential protein detection. Moreover,
      most existing studies focused on the local information of proteins in PPI
      networks, while ignoring the influence of indirect protein interactions on
      essentiality. In this paper, we propose a novel method, called Essentiality
      Ranking (EssRank in short), to boost the accuracy of essential protein detection.
      To deal with the inaccuracy of PPI data, confidence scores of interactions are
      evaluated by integrating various biological information. Weighted edge clustering
      coefficient (WECC), considering both interaction confidence scores and network
      topology, is proposed to calculate edge weights in PPI networks. The weight of
      each node is evaluated by the sum of WECC values of its linking edges. A random
      walk method, making use of both direct and indirect protein interactions, is then
      employed to calculate protein essentiality iteratively. Experimental results on
      the yeast PPI network show that EssRank outperforms most existing methods,
      including the most commonly-used centrality measures (SC, DC, BC, CC, IC, EC),
      topology based methods (DMNC and NC) and the data integrating method IEW.

PMID- 28504947
TI  - Robust Wireless Power Transmission to mm-Sized Free-Floating Distributed
      Implants.
AB  - This paper presents an inductive link for wireless power transmission (WPT) to mm
      sized free-floating implants (FFIs) distributed in a large three-dimensional
      space in the neural tissue that is insensitive to the exact location of the
      receiver (Rx). The proposed structure utilizes a high-Q resonator on the target
      wirelessly powered plane that encompasses randomly positioned multiple FFIs, all
      powered by a large external transmitter (Tx). Based on resonant WPT fundamentals,
      we have devised a detailed method for optimization of the FFIs and explored
      design strategies and safety concerns, such as coil segmentation and specific
      absorption rate limits using realistic finite element simulation models in HFSS
      including head tissue layers, respectively. We have built several FFI prototypes
      to conduct accurate measurements and to characterize the performance of the
      proposed WPT method. Measurement results on 1-mm receivers operating at 60 MHz
      show power transfer efficiency and power delivered to the load at 2.4% and 1.3
      mW, respectively, within 14-18 mm of Tx-Rx separation and 7 cm2 of brain surface.

PMID- 28504948
TI  - Substructural Regularization With Data-Sensitive Granularity for Sequence
      Transfer Learning.
AB  - Sequence transfer learning is of interest in both academia and industry with the
      emergence of numerous new text domains from Twitter and other social media tools.
      In this paper, we put forward the data-sensitive granularity for transfer
      learning, and then, a novel substructural regularization transfer learning model
      (STLM) is proposed to preserve target domain features at substructural
      granularity in the light of the condition of labeled data set size. Our model is
      underpinned by hidden Markov model and regularization theory, where the
      substructural representation can be integrated as a penalty after measuring the
      dissimilarity of substructures between target domain and STLM with relative
      entropy. STLM can achieve the competing goals of preserving the target domain
      substructure and utilizing the observations from both the target and source
      domains simultaneously. The estimation of STLM is very efficient since an
      analytical solution can be derived as a necessary and sufficient condition. The
      relative usability of substructures to act as regularization parameters and the
      time complexity of STLM are also analyzed and discussed. Comprehensive
      experiments of part-of-speech tagging with both Brown and Twitter corpora fully
      justify that our model can make improvements on all the combinations of source
      and target domains.

PMID- 28504949
TI  - Cascaded Subpatch Networks for Effective CNNs.
AB  - Conventional convolutional neural networks use either a linear or a nonlinear
      filter to extract features from an image patch (region) of spatial size
      (typically, is small and is equal to , e.g., is 5 or 7). Generally, the size of
      the filter is equal to the size of the input patch. We argue that the
      representational ability of equal-size strategy is not strong enough. To overcome
      the drawback, we propose to use subpatch filter whose spatial size is smaller
      than . The proposed subpatch filter consists of two subsequent filters. The first
      one is a linear filter of spatial size and is aimed at extracting features from
      spatial domain. The second one is of spatial size and is used for strengthening
      the connection between different input feature channels and for reducing the
      number of parameters. The subpatch filter convolves with the input patch and the
      resulting network is called a subpatch network. Taking the output of one subpatch
      network as input, we further repeat constructing subpatch networks until the
      output contains only one neuron in spatial domain. These subpatch networks form a
      new network called the cascaded subpatch network (CSNet). The feature layer
      generated by CSNet is called the csconv layer. For the whole input image, we
      construct a deep neural network by stacking a sequence of csconv layers.
      Experimental results on five benchmark data sets demonstrate the effectiveness
      and compactness of the proposed CSNet. For example, our CSNet reaches a test
      error of 5.68% on the CIFAR10 data set without model averaging. To the best of
      our knowledge, this is the best result ever obtained on the CIFAR10 data set.

PMID- 28504950
TI  - Graph Regularized Restricted Boltzmann Machine.
AB  - The restricted Boltzmann machine (RBM) has received an increasing amount of
      interest in recent years. It determines good mapping weights that capture useful
      latent features in an unsupervised manner. The RBM and its generalizations have
      been successfully applied to a variety of image classification and speech
      recognition tasks. However, most of the existing RBM-based models disregard the
      preservation of the data manifold structure. In many real applications, the data
      generally reside on a low-dimensional manifold embedded in high-dimensional
      ambient space. In this brief, we propose a novel graph regularized RBM to capture
      features and learning representations, explicitly considering the local manifold
      structure of the data. By imposing manifold-based locality that preserves
      constraints on the hidden layer of the RBM, the model ultimately learns sparse
      and discriminative representations. The representations can reflect data
      distributions while simultaneously preserving the local manifold structure of
      data. We test our model using several benchmark image data sets for unsupervised
      clustering and supervised classification problem. The results demonstrate that
      the performance of our method exceeds the state-of-the-art alternatives.

PMID- 28504951
TI  - A Sequential Learning Approach for Scaling Up Filter-Based Feature Subset
      Selection.
AB  - Increasingly, many machine learning applications are now associated with very
      large data sets whose sizes were almost unimaginable just a short time ago. As a
      result, many of the current algorithms cannot handle, or do not scale to, today's
      extremely large volumes of data. Fortunately, not all features that make up a
      typical data set carry information that is relevant or useful for prediction, and
      identifying and removing such irrelevant features can significantly reduce the
      total data size. The unfortunate dilemma, however, is that some of the current
      data sets are so large that common feature selection algorithms-whose very goal
      is to reduce the dimensionality-cannot handle such large data sets, creating a
      vicious cycle. We describe a sequential learning framework for feature subset
      selection (SLSS) that can scale with both the number of features and the number
      of observations. The proposed framework uses multiarm bandit algorithms to
      sequentially search a subset of variables, and assign a level of importance for
      each feature. The novel contribution of SLSS is its ability to naturally scale to
      large data sets, evaluate such data in a very small amount of time, and be
      performed independently of the optimization of any classifier to reduce
      unnecessary complexity. We demonstrate the capabilities of SLSS on synthetic and
      real-world data sets.

PMID- 28504952
TI  - Exponential Synchronization of Networked Chaotic Delayed Neural Network by a
      Hybrid Event Trigger Scheme.
AB  - This paper is concerned with the exponential synchronization for master-slave
      chaotic delayed neural network with event trigger control scheme. The model is
      established on a network control framework, where both external disturbance and
      network-induced delay are taken into consideration. The desired aim is to
      synchronize the master and slave systems with limited communication capacity and
      network bandwidth. In order to save the network resource, we adopt a hybrid event
      trigger approach, which not only reduces the data package sending out, but also
      gets rid of the Zeno phenomenon. By using an appropriate Lyapunov functional, a
      sufficient criterion for the stability is proposed for the error system with
      extended ( , , )-dissipativity performance index. Moreover, hybrid event trigger
      scheme and controller are codesigned for network-based delayed neural network to
      guarantee the exponential synchronization between the master and slave systems.
      The effectiveness and potential of the proposed results are demonstrated through
      a numerical example.

PMID- 28504953
TI  - Adaptive Seizure Onset Detection Framework Using a Hybrid PCA-CSP Approach.
AB  - Epilepsy is one of the most common neurological disorders in the world. Prompt
      detection of seizure onset from electroencephalogram (EEG) signals can improve
      the treatment of epileptic patients. This paper presents a new adaptive patient
      specific seizure onset detection framework that dynamically selects a feature
      from enhanced EEG signals to discriminate seizures from normal brain activity.
      The proposed framework employs principal component analysis and common spatial
      patterns to enhance the EEG signals and uses the extracted discriminative feature
      as an input for adaptive distance-based change point detector to identify the
      seizure onsets. Experimental results from the Children's Hospital Boston
      Massachusetts Institute of Technology (CHB-MIT) dataset show the computational
      efficiency of the proposed method (analyzing EEG signals in a time window of 3 s
      within 0.1 s using a Core i7 PC) while providing comparable results to the
      existing methods in terms of average sensitivity, latency, and false detection
      rate. The proposed method is advantageous for real-time monitoring of epileptic
      patients and could be used to improve early diagnosis and treatment of patients
      suffering from recurrent seizures.

PMID- 28504954
TI  - Automatic Fetal Head Circumference Measurement in Ultrasound Using Random Forest
      and Fast Ellipse Fitting.
AB  - Head circumference (HC) is one of the most important biometrics in assessing
      fetal growth during prenatal ultrasound examinations. However, the manual
      measurement of this biometric by doctors often requires substantial experience.
      We developed a learning-based framework that used prior knowledge and employed a
      fast ellipse fitting method (ElliFit) to measure HC automatically. We first
      integrated the prior knowledge about the gestational age and ultrasound scanning
      depth into a random forest classifier to localize the fetal head. We further used
      phase symmetry to detect the center line of the fetal skull and employed ElliFit
      to fit the HC ellipse for measurement. The experimental results from 145 HC
      images showed that our method had an average measurement error of 1.7 mm and
      outperformed traditional methods. The experimental results demonstrated that our
      method shows great promise for applications in clinical practice.

PMID- 28504955
TI  - Three-Dimensional Intravascular Reconstruction Techniques Based on Intravascular
      Ultrasound: A Technical Review.
AB  - Intravascular ultrasound (IVUS) imaging provides two-dimensional (2-D) real-time
      luminal and transmural cross-sectional images of intravascular vessels with
      detailed pathological information. It has offered significant advantages in terms
      of diagnosis and guidance and has been increasingly introduced from coronary
      interventions into more generalized endovascular surgery. However, IVUS itself
      does not provide spatial pose information for its generated images, making it
      difficult to construct a 3-D intravascular visualization. To address this
      limitation, IVUS imaging-driven 3-D intravascular reconstruction techniques have
      been developed. These techniques enable accurate diagnosis and quantitative
      measurements of intravascular diseases to facilitate optimal treatment
      determination. Such reconstruction extends the IVUS imaging modality from pure
      diagnostic assistance to intraoperative navigation and guidance and supports both
      therapeutic options and interventional operations. This paper presents a
      comprehensive survey of technological advances and recent progress on IVUS
      imaging-based 3-D intravascular reconstruction and its state-of-the-art
      applications. Limitations of existing technologies and prospects of new
      technologies are also discussed.

PMID- 28504965
TI  - HDAC/IKK inhibition therapies in solid tumors.

PMID- 28504966
TI  - Functional characterization of the lysosomal membrane protein TMEM192 in mice.
AB  - The Transmembrane protein 192 (TMEM192) is a lysosomal/late endosomal protein
      initially discovered by organellar proteomics. TMEM192 exhibits four
      transmembrane segments with cytosolic N- and C-termini and forms homodimers.
      Devoid of significant homologies, the molecular function of TMEM192 is currently
      unknown. Upon TMEM192 knockdown in hepatoma cells, a dysregulation of autophagy
      and increased apoptosis were reported. Here, we aimed to define the physiological
      role of TMEM192 by analysing consequences of TMEM192 ablation in mice. Therefore,
      we compared the biochemical properties of murine TMEM192 to those of the human
      orthologue. We reveal lysosomal residence of murine TMEM192 and demonstrate
      ubiquitous tissue expression. In brain, TMEM192 expression was pronounced in the
      hippocampus but also present in the cortex and cerebellum, as analysed based on a
      lacZ reporter allele. Murine TMEM192 undergoes proteolytic processing in a tissue
      specific manner. Thereby, a 17 kDa fragment is generated which was detected in
      most murine tissues except liver. TMEM192 processing occurs after lysosomal
      targeting by pH-dependent lysosomal proteases. TMEM192-/- murine embryonic
      fibroblasts (MEFs) exhibited a regular morphology of endo-/lysosomes and were
      capable of performing autophagy and lysosomal exocytosis. Histopathological,
      ultrastructural and biochemical analyses of all major tissues of TMEM192-/- mice
      demonstrated normal lysosomal functions without apparent lysosomal storage.
      Furthermore, the abundance of the major immune cells was comparable in TMEM192-/-
      and wild type mice. Based on this, we conclude that under basal conditions in
      vivo the loss of TMEM192 can be efficiently compensated by alternative pathways.
      Further studies will be required to decipher its molecular function.

PMID- 28504972
TI  - Temperature dependent spectroscopic and excited state dynamics of 3
      hydroxychromones with electron donor and acceptor substituents.
AB  - We have studied the photophysical and photochemical behavior of three compounds
      derived from 3-hydroxychromone (3-HC), capable of undergoing excited state proton
      transfer (ESIPT). The compounds have two substituents, located in positions 2 and
      7, one on each ring of the 3-HC heterocycle. The substituent pattern shows
      different electron donating and acceptor features. The compounds were studied by
      absorption and emission spectroscopy, steady state anisotropy, and time resolved
      emission spectroscopy (TRES) as a function of temperature. Results were
      interpreted using time dependent density functional theory calculations. Compared
      to reference compounds of 3-HC substituted only in the 2 position, the compounds
      show similar absorption and emission spectra, shifted 20-30 nm to higher
      wavelengths due to extended conjugation. TRES shows the existence of ESIPT in the
      thermodynamic equilibrium regime. This process is endothermic in all three
      compounds. The different behavior compared to monosubstituted 3-HC is attributed
      to the extended conjugation and to the electron donor acceptor character of the
      substituents, which has a more pronounced effect when the electron acceptor is
      located in position 2.

PMID- 28504971
TI  - Robust tactile sensory responses in finger area of primate motor cortex relevant
      to prosthetic control.
AB  - OBJECTIVE: Challenges in improving the performance of dexterous upper-limb brain
      machine interfaces (BMIs) have prompted renewed interest in quantifying the
      amount and type of sensory information naturally encoded in the primary motor
      cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to
      tactile stimulation, as well as passive and active movement of the limbs.
      However, recent work in this area has focused primarily on proprioception. Here
      we examined instead how tactile somatosensation of the hand and fingers is
      represented in M1. APPROACH: We recorded multi- and single units and thresholded
      neural activity from macaque M1 while gently brushing individual finger pads at 2
      Hz. We also recorded broadband neural activity from electrocorticogram (ECoG)
      grids placed on human motor cortex, while applying the same tactile stimulus.
      MAIN RESULTS: Units displaying significant differences in firing rates between
      individual fingers (p  <  0.05) represented up to 76.7% of sorted multiunits
      across four monkeys. After normalizing by the number of channels with significant
      motor finger responses, the percentage of electrodes with significant tactile
      responses was 74.9%  +/-  24.7%. No somatotopic organization of finger preference
      was obvious across cortex, but many units exhibited cosine-like tuning across
      multiple digits. Sufficient sensory information was present in M1 to correctly
      decode stimulus position from multiunit activity above chance levels in all
      monkeys, and also from ECoG gamma power in two human subjects. SIGNIFICANCE:
      These results provide some explanation for difficulties experienced by motor
      decoders in clinical trials of cortically controlled prosthetic hands, as well as
      the general problem of disentangling motor and sensory signals in primate motor
      cortex during dextrous tasks. Additionally, examination of unit tuning during
      tactile and proprioceptive inputs indicates cells are often tuned differently in
      different contexts, reinforcing the need for continued refinement of BMI training
      and decoding approaches to closed-loop BMI systems for dexterous grasping.

PMID- 28504973
TI  - First-principles calculations of the magnetic and electronic structures of MnP
      under pressure.
AB  - Manganese monophosphide (MnP) shows complicated magnetic states varying with both
      temperature and pressure. We calculate the magnetic and electronic structures of
      MnP at different pressures using first-principles methods and obtain spiral
      ground states whose propagation vector changes from the c-axis at low pressure to
      the b-axis at high pressure. In between, we find a ferromagnetic state, as
      observed in the experimental phase diagram. The propagation vector of the spiral
      states is found to vary nonmonotonically with pressure, consistent with neutron
      measurements. Our results indicate that the complicated magnetic phase diagram
      originates from a delicate competition between neighboring exchange interactions
      between the Mn-ions. At all pressures, the electronic structures indicate the
      existence of quasi-one-dimensional charge carriers, which appear in the
      ferromagnetic state and become gapped in the spiral state, and anisotropic three
      dimensional charge carriers. We argue that this two-fluid behavior originates
      from the special crystal structure of MnP and may be relevant for understanding
      the pairing mechanism of the superconductivity at the border of the high pressure
      spiral phase.

PMID- 28504970
TI  - Osteoclast proton pump regulator Atp6v1c1 enhances breast cancer growth by
      activating the mTORC1 pathway and bone metastasis by increasing V-ATPase
      activity.
AB  - It is known that V-ATPases (vacuolar H+-ATPase) are involved in breast cancer
      growth and metastasis. Part of this action is similar to their role in
      osteoclasts, where they're involved in extracellular acidification and matrix
      destruction; however, the roles of their subunits in cancer cell proliferation,
      signaling, and other pro-tumor actions are not well established. Analysis of TCGA
      data shows that V-ATPase subunit Atp6v1c1 is overexpressed or amplified in 34% of
      human breast cancer cases, with a 2-fold decrease in survival at 12 years.
      Whereas other subunits, such as Atp6v1c2 and Atp6v0a3, are overexpressed or
      genomically amplified less often, 6% each respectively, and have less impact on
      survival. Experiments show that lentiviral-shRNA mediated ATP6v1c1 knockdown in
      4T1 mouse mammary cancer cells significantly reduces orthotopic and intraosseous
      tumor growth. ATP6v1c1 knockdown also significantly reduces tumor stimulated bone
      resorption through osteoclastogenesis at the bone and metastasis in vivo, as well
      as V-ATPase activity, proliferation, and mTORC1 activation in vitro. To
      generalize the effects of ATP6v1c1 knockdown on proliferation and mTORC1
      activation we used human cancer cell lines - MCF-7, MDA-MB-231, and MDA-MB-435s.
      ATP6V1C1 knockdown reduced cell proliferation and impaired mTORC1 pathway
      activation in cancer cells but not in the untransformed cell line C3H10T1/2. Our
      study reveals that V-ATPase activity may be mediated through mTORC1 and that
      ATP6v1c1 can be knocked down to block both V-ATPase and mTORC1 activity.

PMID- 28504974
TI  - Diffusion and aggregation of oxygen vacancies in amorphous silica.
AB  - Using density functional theory (DFT) calculations, we investigated oxygen
      vacancy diffusion and aggregation in relation to dielectric breakdown in
      amorphous silicon dioxide (a-SiO2). Our calculations indicate the existence of
      favourable sites for the formation of vacancy dimers and trimers in the amorphous
      network with maximum binding energies of approximately 0.13 eV and 0.18 eV,
      respectively. However, an average energy barrier height for neutral vacancy
      diffusion is found to be about 4.6 eV, rendering this process unfeasible. At
      Fermi level positions above 6.4 eV with respect to the top of the valence band,
      oxygen vacancies can trap up to two extra electrons. Average barriers for the
      diffusion of negative and double negatively charged vacancies are found to be 2.7
      eV and 2.0 eV, respectively. These barriers are higher than or comparable to
      thermal ionization energies of extra electrons from oxygen vacancies into the
      conduction band of a-SiO2. In addition, we discuss the competing pathways for
      electron trapping in oxygen deficient a-SiO2 caused by the existence of intrinsic
      electron traps and oxygen vacancies. These results provide new insights into the
      role of oxygen vacancies in degradation and dielectric breakdown in amorphous
      silicon oxides.

PMID- 28504975
TI  - CE: Original Research: The Experiences of Pregnant Smokers and Their Providers.
AB  - : : Background: The U.S. Department of Health and Human Services' initiative
      Healthy People 2020 targets tobacco use, including smoking during pregnancy, as a
      continuing major health concern in this country. Yet bringing the U.S. Public
      Health Service's 2008 clinical practice guideline, Treating Tobacco Use and
      Dependence, into routine prenatal care remains challenging. Our previous nurse
      managed intervention study of rural pregnant women found no significant cessation
      effect and significant discordance between self-reported smoker status and
      urinary cotinine levels. PURPOSE: The overall purpose of this follow-up study was
      to increase our understanding of the experiences of pregnant smokers and their
      providers. No qualitative studies could be found that simultaneously explored the
      experiences of both groups. DESIGN AND METHODS: This qualitative descriptive
      study used focus group methodology. Nine focus groups were held in two counties
      in upper New York State; six groups consisted of providers and three consisted of
      pregnant women. Four semistructured questions guided the group discussions, which
      were audiotaped and transcribed verbatim. Transcripts were read and coded
      independently by six investigators. Themes were identified using constant
      comparative analysis and were validated using the consensus process. RESULTS: The
      total sample consisted of 66 participants: 45 providers and 21 pregnant women.
      Most of the providers were white (93%) and female (93%). A majority worked as RNs
      (71%); the sample included perinatal and neonatal nursery nurses, midwives, and
      physicians. The pregnant women were exclusively white (reflecting the rural
      demographic); the average age was 24 years. All the pregnant women had smoked at
      the beginning of their pregnancies. Four common themes emerged in both the
      provider and the pregnant women groups: barriers to quitting, mixed messages,
      approaches and attitudes, and program modalities. These themes corroborate
      previous findings that cigarette smoking is used for stress relief, especially
      when pregnancy itself is a stressor, and that pregnant women may feel guilty but
      don't want to be nagged or preached to. CONCLUSIONS: These results have
      implications for how smoking cessation programs for pregnant women should be
      designed. Health care providers need to be cognizant of their approaches and
      attitudes when addressing the subject of smoking cessation. Specific educational
      suggestions include "putting a face" to the issue of tobacco use during
      pregnancy. More research is needed on how best to implement the 2008 clinical
      practice guideline in specific populations.

PMID- 28504976
TI  - CE: Antipsychotic Medications.
AB  - : Antipsychotic medications are primarily used to manage various symptoms of
      psychosis. In recent years, more adults-and teenagers-are taking at least one
      type of psychotropic medication, the majority of which are prescribed by primary
      care and family physicians. Because nurses are now caring for people of varying
      ages, and with varying diagnoses, who are taking these types of medications, they
      need to develop a working knowledge of the agents available and know when it's
      appropriate to prescribe them for mental health disorders as well as for
      disorders unrelated to mental health. This article is the first in a series on
      commonly used psychotropic medications.

PMID- 28504977
TI  - An Adolescent Male With Anorexia Nervosa Favorably Responded to Mirtazapine.

PMID- 28504978
TI  - Beyond Googling: The Ethics of Using Patients' Electronic Footprints in
      Psychiatric Practice.
AB  - Electronic communications are an increasingly important part of people's lives,
      and much information is accessible through such means. Anecdotal clinical reports
      indicate that mental health professionals are beginning to use information from
      their patients' electronic activities in treatment and that their data-gathering
      practices have gone far beyond simply searching for patients online. Both
      academic and private sector researchers are developing mental health applications
      to collect patient information for clinical purposes. Professional societies and
      commentators have provided minimal guidance, however, about best practices for
      obtaining or using information from electronic communications or other online
      activities. This article reviews the clinical and ethical issues regarding use of
      patients' electronic activities, primarily focusing on situations in which
      patients share information with clinicians voluntarily. We discuss the potential
      uses of mental health patients' electronic footprints for therapeutic purposes,
      and consider both the potential benefits and the drawbacks and risks. Whether
      clinicians decide to use such information in treating any particular patient-and
      if so, the nature and scope of its use-requires case-by-case analysis. But it is
      reasonable to assume that clinicians, depending on their circumstances and goals,
      will encounter circumstances in which patients' electronic activities will be
      relevant to, and useful in, treatment.

PMID- 28504979
TI  - Congenital Deafness Alters Sensory Weighting for Postural Control.
AB  - OBJECTIVES: The aim of this study was to examine sensory reweighting for postural
      control in congenitally deaf individuals. DESIGN: We studied 14 controls and 14
      deaf age-matched individuals using a force platform and the modified clinical
      test of sensory interaction and balance protocol. Both groups performed the
      postural tasks without auditory cues (with hearing protectors for controls or
      without hearing devices for the deaf). RESULTS: The results confirmed poorer
      postural stability in the deaf. More importantly, the data suggest that
      congenitally deaf individuals rely more on somatosensory information for postural
      control than controls. CONCLUSIONS: This increased somatosensory reliance may
      increase postural sway when it comes to more challenging postural conditions.

PMID- 28504980
TI  - Hyperchloremia Is Associated With Acute Kidney Injury in Patients With
      Subarachnoid Hemorrhage.
AB  - OBJECTIVE: To assess the prevalence of acute kidney injury in patients with
      subarachnoid hemorrhage patients. DESIGN: Retrospective analysis of all
      subarachnoid hemorrhage admissions. SETTINGS: Neurocritical care unit. PATIENTS:
      All patients with a diagnosis of subarachnoid hemorrhage between 2009 and 2014.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,267 patients included in
      this cohort, 16.7% developed acute kidney injury, as defined by Kidney Disease
      Improving Global Outcome criteria (changes in creatinine only). Compared to
      patients without acute kidney injury, patients with acute kidney injury had a
      higher prevalence of diabetes mellitus (21.2% vs 9.8%; p < 0.001) and
      hypertension (70.3% vs 50.5%; p < 0.001) and presented with higher admission
      creatinine concentrations (1.21 +/- 0.09 vs 0.81 +/- 0.01 mg/dL [mean +/- SD],
      respectively; p < 0.001). Patients with acute kidney injury also had higher mean
      serum chloride and sodium concentrations during their ICU stay (113.4 +/- 0.6 vs
      107.1 +/- 0.2 mmol/L and 143.3 +/- 0.4 vs 138.8 +/- 0.1 mmol/L, respectively; p <
      0.001 for both), but similar chloride exposure. The mortality rate was also
      significantly higher in patients with acute kidney injury (28.3% vs 6.1% in the
      non-acute kidney injury group [p < 0.001]). Logistic regression analysis revealed
      that only male gender (odds ratio, 1.82; 95% CI, 1.28-2.59), hypertension (odds
      ratio, 1.64; 95% CI, 1.11-2.43), diabetes mellitus (odds ratio, 1.88; 95% CI,
      1.19-2.99), abnormal baseline creatinine (odds ratio, 2.48; 95% CI, 1.59-3.88),
      and increase in mean serum chloride concentration (per 10 mmol/L; odds ratio,
      7.39; 95% CI, 3.44-18.23), but not sodium, were associated with development of
      acute kidney injury. Kidney recovery was noted in 78.8% of the cases. Recovery
      reduced mortality compared to non-recovering subgroup (18.6% and 64.4%,
      respectively; p < 0.001). CONCLUSIONS: Critically ill patients with subarachnoid
      hemorrhage show a strong association between hyperchloremia and acute kidney
      injury as well as acute kidney injury and mortality.

PMID- 28504981
TI  - Perianal Epidermodysplasia Verruciformis Associated With Human Papillomavirus 5
      After a Renal Transplant.

PMID- 28504982
TI  - Characteristics, in-hospital management and outcome of late acute ST-elevation
      myocardial infarction presenters.
AB  - BACKGROUND: Patients with delayed presentation of acute myocardial infarction
      with ST-segment elevation (STEMI) frequently have a poor prognosis but literature
      about acute complications in intensive cardiac care unit (ICCU) and in-hospital
      outcome are still limited. METHODS: All STEMI patients admitted to our
      institution between June 2007 and December 2013 were divided into patients
      presenting more than 12 h after symptom onset (lateSTEMI) and within 12 h
      (STEMI). Baselines clinical features including details about treatment of choice
      were collected. Major acute complications in ICCU and in-hospital mortality were
      the main end-points. RESULTS: A total of 1372 patients were included, 147 (10.8%)
      were lateSTEMI. In ICCU lateSTEMI patients compared with STEMI patients
      experienced more frequently heart failure (75, 51.2% vs. 298, 24.3%; P < 0.001),
      atrial fibrillation (26, 17.7% vs. 130, 10.6%; P = 0.011), complete
      atrioventricular block (16, 10.9% vs. 63, 5.1%; P = 0.005), stroke (5, 3.4% vs.
      5, 0.4%; P < 0.001), myocardial rupture (6, 4.1% vs. 3, 0.2%; P < 0.001), with
      higher administration of noninvasive ventilation support therapy (13, 9.8% vs.
      44, 3.6%; P = 0.001) and the intra-aortic balloon counter-pulsation use (14,
      10.3% vs. 102, 8.3%; P = 0.038). Intrahospital mortality was significantly higher
      in the lateSTEMI group (19, 13.4% vs. 69, 5.6%; P = 0.001). At the multiple
      regression analysis age [odds ratio (OR) 2.2 (1.46-2.92.; P = 0.01)], diabetes
      [OR 2.37 (1.38-4.07); P = 0.002] intra-aortic balloon counter-pulsation
      implantation [OR 2.78 (1.30-5.9); P = 0.03] and late presentation more than 12 h
      [2.52 (1.35-4.69); P = 0.001] resulted independently correlated with in-hospital
      mortality while a successful percutaneous coronary intervention procedure was
      protective [OR 0.15 (0.08-0.27); P = 0.003; all 95% confidence interval).
      CONCLUSION: Late presenters STEMI patients present a worse risk profile and
      prognosis compared with patients who arrive less than 12 h from onset of
      symptoms. Because of the presence of serious complications such as heart rupture
      or stroke a careful clinic and echocardiographic monitoring is strongly advisable
      in these population.

PMID- 28504983
TI  - Serum inhibitory factor 1, high-density lipoprotein and cardiovascular diseases.
AB  - PURPOSE OF REVIEW: The atheroprotective properties of HDL are supported by
      epidemiological and preclinical research. However, the results of interventional
      trials paradoxically indicate that drugs increasing HDL-cholesterol (HDL-C) do
      not reduce coronary artery disease (CAD) risk. Moreover, Mendelian randomization
      studies have shown no effect of HDL-C-modifying variants on CAD outcome. Thus,
      the protective effects of HDL particles are more governed by their functional
      status than their cholesterol content. In this context, any successful clinical
      exploitation of HDL will depend on the identification of HDL-related biomarkers,
      better than HDL-C level, for assessing cardiovascular risk and monitoring
      responses to treatment. RECENT FINDINGS: Recent studies have enlightened the role
      of ecto-F1-ATPase as a cell surface receptor for apoA-I, the major apolipoprotein
      of HDL, involved in the important metabolic and vascular atheroprotective
      functions of HDL. In the light of these findings, the clinical relevance of ecto
      F1-ATPase in humans has recently been supported by the identification of serum F1
      ATPase inhibitor (IF1) as an independent determinant of HDL-C, CAD risk and
      cardiovascular mortality in CAD patients. SUMMARY: Serum IF1 measurement might be
      used as a novel HDL-related biomarker to better stratify risk in high-risk
      populations or to determine pharmacotherapy.

PMID- 28504984
TI  - Melding a High-Risk Patient for Continuous Flow Left Ventricular Assist Device
      into a Low-Risk Patient.
AB  - The model for end-stage liver disease (MELD) has been used as a predictor of
      mortality after left ventricular assist device (LVAD) placement. However,
      improvement or worsening of MELD and how those changes affect outcomes is
      unknown. We performed a retrospective analysis of 244 patients implanted with a
      continuous flow (CF) LVAD. Patients were dichotomized at admission into low- or
      high-risk categories using a cutoff of MELD >= 19, and they were reclassified at
      day of implant forming four groups: Group LL (low to low, remained low risk), LH
      (low to high, worsened to high risk), HH (high to high, remained high risk), and
      HL (high to low, improved to low risk). Patients who improved to a low risk
      (group HL) had the same 1 year survival as those that remained low risk (group
      LL; 80% vs. 77%; p = 0.6). However, patients who were initially classified as low
      risk and worsened to a high risk (group LH) had a survival that was worse than
      those that were consistently high risk (group HH; 55% vs. 10%; p = 0.01). Model
      for end-stage liver disease reclassification after adjusting for commonly
      attributed risk factors remained an independent predictor for mortality,
      including patients classified as Interagency Registry for Mechanically Assisted
      Circulatory Support (INTERMACS) 1 and 2. In conclusion, our MELD score
      reclassification is an independent and powerful predictor of mortality in
      patients undergoing LVAD implantation.

PMID- 28504985
TI  - Current opinion in otolaryngology and head and neck surgery: frontal sinus
      fractures.
AB  - PURPOSE OF REVIEW: The purpose of this manuscript is to review the current
      literature regarding the management of frontal sinus fractures and offer the
      authors opinion on the current management of these traumatic injuries. We
      evaluate recently proposed management algorithms as well as novel surgical
      approaches reported within the last few years. RECENT FINDINGS: Patient selection
      for sinus sparing treatment modalities is balanced between fracture severity,
      involved structures, and reliable patient surveillance. Minimally invasive,
      aesthetically favorable approaches grow in diversity for anterior table
      fractures. For fractures of the posterior sinus wall and nasofrontal outflow
      tract, the literature focuses on sinus sparing surgery, as well as better
      defining the patients in which obliteration and/or cranialization is appropriate.
      SUMMARY: Lack of large patient cohorts and follow-up limits generalizability of
      frontal sinus fracture research, and the ability to develop national guidelines
      of management. Evidence-based literature shows growing support for conservative
      management and sinus preservation. Improvements in frontal sinus fracture
      classification schemes, surgical technique, and patient selection direct this
      treatment paradigm shift.

PMID- 28504986
TI  - Cosmetic bone contouring.
AB  - PURPOSE OF REVIEW: In recent years, cosmetic bone contouring surgery has become
      increasingly popular, especially in East Asian countries. These procedures are
      also being requested by patients in the United States at an increasing rate. The
      purpose of this study is to provide an overview of what is involved with these
      procedures and their potential complications. RECENT FINDINGS: In some cultures,
      a wide jaw and a square face are aesthetically unpleasing, whereas an ovoid or
      'melon seed face' is thought to be feminine, delicate and beautiful. Mandibular
      angloplasty, mandibular lateral cortex excision, reduction malarplasty, as well
      as genioplasty may be performed to alter the facial contour and bring about
      dramatic results. SUMMARY: Whether a surgeon choses to incorporate these
      procedures into practice or not, the craniofacial surgeons should be familiar
      with the procedures as well as the potential complications.

PMID- 28504987
TI  - Secondary reconstruction of maxillofacial trauma.
AB  - PURPOSE OF REVIEW: Craniomaxillofacial trauma is one of the most complex clinical
      conditions in contemporary maxillofacial surgery. Vital structures and possible
      functional and esthetic sequelae are important considerations following this type
      of trauma and intervention. Despite the best efforts of the primary surgery,
      there are a group of patients that will have poor outcomes requiring secondary
      reconstruction to restore form and function. The purpose of this study is to
      review current concepts on secondary reconstruction to the maxillofacial complex.
      RECENT FINDINGS: The evaluation of a posttraumatic patient for a secondary
      reconstruction must include an assessment of the different subunits of the upper
      face, middle face, and lower face. Virtual surgical planning and surgical guides
      represent the most important innovations in secondary reconstruction over the
      past few years. Intraoperative navigational surgery/computed-assisted navigation
      is used in complex cases. Facial asymmetry can be corrected or significantly
      improved by segmentation of the computerized tomography dataset and mirroring of
      the unaffected side by means of virtual surgical planning. Navigational
      surgery/computed-assisted navigation allows for a more precise surgical
      correction when secondary reconstruction involves the replacement of extensive
      anatomical areas. The use of technology can result in custom-made replacements
      and prebent plates, which are more stable and resistant to fracture because of
      metal fatigue. SUMMARY: Careful perioperative evaluation is the key to positive
      outcomes of secondary reconstruction after trauma. The advent of technological
      tools has played a capital role in helping the surgical team perform a given
      treatment plan in a more precise and predictable manner.

PMID- 28504988
TI  - The Labor Analgesia Requirements in Nulliparous Women Randomized to Epidural
      Catheter Placement in a High or Low Intervertebral Space.
AB  - BACKGROUND: We hypothesized that an epidural catheter placed in a lower vertebral
      interspace will require less medication for labor analgesia. METHODS: Nulliparous
      women requesting neuraxial labor analgesia were randomized to epidural catheter
      placement at the ultrasound-confirmed L1-2 or L4-5 interspace. Patient-controlled
      epidural analgesia and breakthrough manual epidural boluses of 10 mL of 0.125%
      bupivacaine with 50 ug of fentanyl or 8 mL of 2% lidocaine were utilized.
      Abdominal and perineal pain scores were assessed at 30 and 60 minutes after
      standardized initiation of epidural analgesia. Pain scores during pushing were
      assessed after delivery. The primary outcome was the proportion of patients
      requiring manual boluses and was compared using a chi test. Secondarily, we
      analyzed the number of boluses given in early (up to 4 hours before delivery)
      versus late labor using chi tests and the pain scores using Mann-Whitney U tests,
      with adjustment of P values for multiple testing. RESULTS: We analyzed 148
      patients. Overall, the percentage of patients in the low versus high groups who
      required manual boluses was 46% vs 51% (P = 1.0). For the 56 patients in each
      group who delivered vaginally, 22 (52%) vs 20 (48%) manual boluses were given to
      the low epidural group in early versus late labor, compared to 9 (20%) vs 36
      (80%) in the high epidural group (P = .014). There was no statistical difference
      in patient-controlled epidural analgesia requirements or patient satisfaction.
      Comparing the low versus high groups, the median (interquartile range) pain
      scores were: 3 (1, 6) vs 0 (0, 2) (P = .013) at 30 minutes and 1 (1, 3) vs 0 (0,
      1) (P = .013) at 60 minutes for abdominal pain; 0 (0, 2) vs 1 (1, 3) (P = .36)
      and 0 (0, 1) vs 1 (1, 3) (P = .014) at these same time points for perineal pain;
      and 1 (0, 5) vs 0 (0, 3) (P = .9) for abdominal and 2 (0, 5) vs 4 (1, 8) (P =
      .025) for perineal pain during pushing. The percentage of patients who underwent
      instrumental delivery was 15% vs 5% (P = .06) for the low versus high group.
      CONCLUSIONS: An L4-5 epidural catheter initially provides less relief of
      abdominal pain but more relief of perineal labor pain. Patients with an L4-5
      catheter require more manual boluses during early labor but less during late
      labor. The possible association of low epidural catheters with instrumental
      delivery merits further investigation.

PMID- 28504989
TI  - Structural Behavior of the Endothelial Glycocalyx Is Associated With
      Pathophysiologic Status in Septic Mice: An Integrated Approach to Analyzing the
      Behavior and Function of the Glycocalyx Using Both Electron and Fluorescence
      Intravital Microscopy.
AB  - BACKGROUND: The endothelial surface layer (ESL) regulates vascular permeability
      to maintain fluid homeostasis. The glycocalyx (GCX), which has a complex and
      fragile ultrastructure, is an important component of the ESL. Abnormalities of
      the GCX have been hypothesized to trigger pathological hyperpermeability. Here,
      we report an integrated in vivo analysis of the morphological and functional
      properties of the GCX in a vital organ. METHODS: We examined the behavior of the
      ESL and GCX, using both electron microscopy (EM) and intravital microscopy (IVM).
      We also compared morphological changes in the ESL of mouse skin in a glycosidase
      treated and control group. Combined approaches were also used to examine both
      morphology and function in a lipopolysaccharide-induced septic model and the
      pathophysiological features of leukocyte-endothelial interactions and in vivo
      vascular permeability. RESULTS: Using IVM, we identified an illuminated part of
      the ESL as the GCX and confirmed our observation using morphological and
      biochemical means. In septic mice, we found that the GCX was thinner than in
      nonseptic controls in both an EM image analysis (0.98 +/- 2.08 nm vs 70.68 +/-
      36.36 nm, P< .001) and an IVM image analysis (0.36 +/- 0.15 MUm vs 1.07 +/- 0.39
      MUm, P< .001). Under septic conditions, syndecan-1, a representative core protein
      of the GCX, was released into the blood serum at a higher rate in septic animals
      (7.33 +/- 3.46 ng/mL) when compared with controls (below the limit of detection,
      P< .001). Significant increases in leukocyte-endothelial interactions, defined as
      the numbers of rolling or firm-sticking leukocytes, and molecular
      hyperpermeability to the interstitium were also observed after GCX shedding in
      vivo. CONCLUSIONS: Using IVM, we visualized an illuminated part of the ESL layer
      that was subsequently confirmed as the GCX using EM. Severe sepsis induced
      morphological degradation of the GCX, accompanied by shedding of the syndecan-1
      core protein and an increase in leukocyte-endothelial interactions affecting the
      vascular permeability. Our in vivo model describes a new approach to deciphering
      the relationship between structural and functional behaviors of the GCX.

PMID- 28504990
TI  - A Structured Transfer of Care Process Reduces Perioperative Complications in
      Cardiac Surgery Patients.
AB  - INTRODUCTION: Serious complications are common during the intensive care of
      postoperative cardiac surgery patients. Some of these complications may be
      influenced by communication during the process of handover of care from the
      operating room to the intensive care unit (ICU) team. A structured transfer of
      care process may reduce the rate of communication errors and perioperative
      complications. METHODS: We hypothesized that a collaborative, comprehensive,
      structured handover of care from the intraoperative team to the ICU team would
      reduce a specific set of postoperative complications. We tested this hypothesis
      by developing and introducing a comprehensive multidisciplinary transfer of care
      process. We measured patient outcomes before and after the intervention using a
      linkage between 2 care databases: an Anesthesia Information Management System and
      a critical care complication registry database. RESULTS: There were 1127 total
      postoperative cardiac surgery admissions during the study period, 550 before and
      577 after the intervention. There was no statistical difference between overall
      complications before and after the intervention (P = .154). However, there was a
      statistically significant reduction in preventable complications after the
      intervention (P = .023). DISCUSSION: The main finding of this investigation is
      that the introduction of a collaborative, comprehensive transfer of care process
      from the operating room to the ICU was associated with patients suffering fewer
      preventable complications.

PMID- 28504991
TI  - Tablet e-Logbooks: Four Thousand Clinical Cases and Complications e-Logged by 14
      Nondoctor Anesthesia Providers in Nepal.
AB  - BACKGROUND: To meet the need for essential surgery across rural Nepal, anesthesia
      at district level is delivered by nondoctor anesthetists. They require support to
      maintain confidence and competence, and upgraded professional registration to
      secure their status. To meet these needs, a distance-blended learning course was
      pioneered and delivered. A core course requirement was to log all clinical cases;
      these were logged on a new e-logbook. METHODS: Fourteen nondoctor anesthesia
      providers working in 12 different districts across Nepal were enrolled in the 1
      year course. The course is based on self-completion on a tablet loaded with new
      learning modules, a resource library, and a case logbook. Continuous educational
      mentoring was provided by anesthesiologists by phone and email. The logbook
      included preanesthesia assessment and interventions, American Society of
      Anesthesiologists (ASA) grading, types of cases and anesthesia given, monitors
      used, complications, outcomes and free text remarks. Cases were uploaded monthly
      to a database, and mentors reviewed all logbook entries. RESULTS: The 14
      nondoctor anesthesia providers were widely distributed across the country in
      district, zonal, community, and mission hospitals, and had different levels of
      clinical experience and caseloads. Logbooks and uploads were regularly completed
      without difficulty; 1% cases were entered incompletely with no case details
      provided. A total of 4143 cases were recorded. Annual caseload per nondoctor
      anesthesia provider ranged from 50 to 788, the majority of which were under
      spinal anesthesia; 34% of the total cases were cesarean deliveries, of which 99%
      received spinal anesthesia. Fifty gastrointestinal laparotomies (1% total) were
      recorded. Ninety-one percent of cases were ASA I, 0.8% ASA III/IV. Pulse oximetry
      was used in 98% of cases. Complications were recorded in 6% of cases; the most
      common were circulation problems (69%) including hypotension and occasional
      bradycardia after spinal anesthesia. Airway complications were usually under
      ketamine anesthesia requiring basic airway maneuvers; 4 difficult intubations
      were recorded under general anesthesia. Anesthesia outcomes were good with
      overall mortality of 0.1% (total 4 cases). Causes of death included severe
      preeclampsia, sepsis postlaparotomy, and patients with multiorgan failure for
      minor procedure. CONCLUSIONS: The tablet-based electronic anesthesia logbook was
      successfully used to record cases, complications, and outcomes across rural
      Nepal. The nondoctor anesthesia providers had trust and confidence in recording
      outcomes. It remains to be tested whether an e-logbook would be routinely
      completed outside of a specific training course. Such a logbook could be
      incorporated into all continuous professional development programs for rural
      nondoctor anesthetists.

PMID- 28504992
TI  - Trends in Perioperative Practice and Resource Utilization in Patients With
      Obstructive Sleep Apnea Undergoing Joint Arthroplasty.
AB  - BACKGROUND: Emerging evidence associating obstructive sleep apnea (OSA) with
      adverse perioperative outcomes has recently heightened the level of awareness
      among perioperative physicians. In particular, estimates projecting the high
      prevalence of this condition in the surgical population highlight the necessity
      of the development and adherence to "best clinical practices." In this context, a
      number of expert panels have generated recommendations in an effort to provide
      guidance for perioperative decision-making. However, given the paucity of
      insights into the status of the implementation of recommended practices on a
      national level, we sought to investigate current utilization, trends, and the
      penetration of OSA care-related interventions in the perioperative management of
      patients undergoing lower joint arthroplasties. METHODS: In this population-based
      analysis, we identified 1,107,438 (Premier Perspective database; 2006-2013) cases
      of total hip and knee arthroplasties and investigated utilization and temporal
      trends in the perioperative use of regional anesthetic techniques, blood oxygen
      saturation monitoring (oximetry), supplemental oxygen administration, positive
      airway pressure therapy, advanced monitoring environments, and opioid
      prescription among patients with and without OSA. RESULTS: The utilization of
      regional anesthetic techniques did not differ by OSA status and overall <25% and
      15% received neuraxial anesthesia and peripheral nerve blocks, respectively.
      Trend analysis showed a significant increase in peripheral nerve block use by
      >50% and a concurrent decrease in opioid prescription. Interestingly, while the
      absolute number of patients with OSA receiving perioperative oximetry,
      supplemental oxygen, and positive airway pressure therapy significantly increased
      over time, the proportional use significantly decreased by approximately 28%,
      36%, and 14%, respectively. A shift from utilization of intensive care to
      telemetry and stepdown units was seen. CONCLUSIONS: On a population-based level,
      the implementation of OSA-targeted interventions seems to be limited with some of
      the current trends virtually in contrast to practice guidelines. Reasons for
      these findings need to be further elucidated, but observations of a dramatic
      increase in absolute utilization with a proportional decrease may suggest
      possible resource constraints as a contributor.

PMID- 28504993
TI  - Red Blood Cell Transfusion and Surgical Site Infection After Colon Resection
      Surgery: A Cohort Study.
AB  - BACKGROUND: Surgical site infections (SSIs) after colon surgery remain a critical
      safety issue. Patients with an SSI have an increased risk of death, prolonged
      hospitalization, and increased costs of care. Red blood cell (RBC) transfusion is
      given during the perioperative period to increase blood oxygen delivery, but it
      is associated with complications, including infection. We hypothesized that RBC
      transfusion would be associated with increased SSI risk in patients undergoing
      colon resection surgery. METHODS: A retrospective cohort study was performed
      using the 2014 National Surgical Quality Improvement Program participant use
      file. Patients who had colon resection surgery were identified using current
      procedural terminology codes. The association between perioperative RBC
      transfusion and superficial and deep incisional SSIs, organ space SSIs, and
      postoperative septic shock was modeled using logistic regression with propensity
      score analysis. RESULTS: Of 23,388 patients who had colon resection surgery, 1845
      (7.9%) received perioperative RBC transfusion. After controlling for confounders
      with propensity score analysis and inverse probability of treatment weighting,
      RBC transfusion had no apparent association with superficial incisional SSI (odds
      ratio [OR], 1.18; 99% confidence interval [CI], 0.48-2.88) or deep incisional SSI
      (OR, 1.47; 99% CI, 0.23-9.43). However, RBC transfusion appeared to be associated
      with increased risk of organ space SSI (OR, 2.93; 99% CI, 1.43-6.01) and septic
      shock (OR, 9.23; 99% CI, 3.53-24.09). CONCLUSIONS: RBC transfusion has no
      apparent association with increased risk for incisional SSIs, but may be
      associated with increased risk for organ space SSI and septic shock after colon
      resection surgery.

PMID- 28504994
TI  - Preoperative Low-Dose Aspirin Exposure and Outcomes After Emergency Neurosurgery
      for Traumatic Intracranial Hemorrhage in Elderly Patients.
AB  - BACKGROUND: Antiplatelet medications are usually discontinued before elective
      neurosurgery, but this is not an option for emergent neurosurgery. We performed a
      retrospective cohort study to examine whether preoperative aspirin use was
      associated with worse outcomes after emergency neurosurgery in elderly patients.
      METHODS: We analyzed all cases of emergency neurosurgical procedures for
      traumatic intracranial hemorrhage from 2008 to 2012 at a level 1 trauma center.
      Demographics, comorbidities, and outcomes were compared for patients >=65 years
      by preoperative aspirin exposure. Exclusion criteria were: (1) polytrauma, (2)
      concomitant use of other preoperative anticoagulants or antiplatelet agents, (3)
      surgical indication other than subdural, extradural, or intraparenchymal
      hemorrhage, and (4) repeat neurosurgical procedures within a single admission.
      Estimated intraoperative blood loss, postprocedural intracranial bleeding
      requiring reoperation, death in hospital, intensive care unit, and hospital
      lengths of stay and perioperative blood product transfusion from 48 hours before
      48 hours after surgery were the study outcomes. We also examined whether platelet
      transfusion had an impact on outcomes for patients on aspirin. RESULTS: The
      cohort included 171 patients. Patients receiving preoperative aspirin (n = 87,
      95% taking 81 mg/day) were the same age as patients not receiving aspirin (n =
      84; 78.3 +/- 7.8 vs 75.9 +/- 7.9 years, P > .05), had slightly higher admission
      Glasgow Coma Scale scores (12.8 +/- 3.4 vs 11.4 +/- 4, P = .02) and tended to
      have more coronary artery disease (P< .05). Adjusted for Glasgow Coma Scale and
      coronary artery disease, patients receiving preoperative aspirin had a higher
      odds of perioperative platelet transfusion (adjusted odds ratio 9.89, 95%
      confidence interval, 4.24-26.25). There were no other differences in outcomes
      between the 2 groups. Preoperative or intraoperative platelet transfusion was not
      associated with better outcomes among aspirin patients. CONCLUSIONS: In patients
      age >=65 years undergoing emergency neurosurgery for traumatic intracranial
      hemorrhage, preoperative low-dose aspirin treatment was not associated with
      increased perioperative bleeding, hospital lengths of stay, or in-hospital
      mortality.

PMID- 28504995
TI  - Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary
      Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.
AB  - BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is
      often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when
      the lung is re-expanded. We hypothesized that remote ischemic preconditioning
      (RIPC) would decrease oxidative lung damage and improve gas exchange in the
      postoperative period. METHODS: We conducted a single-center, randomized, double
      blind trial in patients with nonsmall cell lung cancer undergoing elective lung
      lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately
      after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion
      induced by an ischemia cuff applied on the thigh) and/or control therapy without
      RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC)
      and arterial blood immediately after anesthesia induction and before RIPC and
      surgery (T0, baseline); during operated lung collapse, immediately before
      resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2);
      and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane
      levels in EBC at T1, T2, and T3. Secondary outcomes included the following:
      NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and
      pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory
      index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels
      when compared with controls at T1, T2, and T3 (differences between means and 95%
      confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008;
      and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and
      H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P
      < .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at
      T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2
      hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for
      differences between means: 78 (10-146), 66 (14-118), and 58 (12-104),
      respectively. CONCLUSIONS: Limb RIPC decreased EBC 8-isoprostane levels and other
      oxidative lung injury markers during lung lobectomy. RIPC also improved
      postoperative gas exchange as measured by PaO2/FiO2 ratio.

PMID- 28504996
TI  - Stroke Volume Variation and Pulse Pressure Variation Are Not Useful for
      Predicting Fluid Responsiveness in Thoracic Surgery.
AB  - BACKGROUND: Stroke volume variation (SVV) and pulse pressure variation (PPV) are
      used as indicators of fluid responsiveness, but little is known about the
      usefulness of these dynamic preload indicators in thoracic surgery, which
      involves an open thoracic cavity and 1-lung ventilation (OLV). Therefore, we
      investigated whether SVV and PPV could predict fluid responsiveness, and whether
      the thresholds of these parameters should be adjusted for thoracic surgery.
      METHODS: This was a prospective, controlled study conducted in a tertiary care
      center. Eighty patients scheduled for an elective lobectomy requiring OLV were
      included (n = 40, video-assisted thoracoscopic surgery (VATS); n = 40, open
      thoracotomy). Twenty minutes after opening the thoracic cavity, 7 mL/kg
      hydroxyethyl starch was administered for 30 minutes. Various hemodynamic
      parameters were measured before and after fluid challenge. RESULTS: Among the 80
      patients enrolled in this study, 37% were fluid responders (increase in stroke
      volume index >=10%). SVV before fluid challenge was not different between
      nonresponders and responders (mean +/- SD: 7.1 +/- 2.7% vs 7.4 +/- 2.6%, P =
      .68). This finding was true regardless of whether the surgery involved open
      thoracotomy or VATS. PPV before fluid challenge showed the difference between
      nonresponders and responders (mean +/- SD: 6.9 +/- 3.0% vs 8.4 +/- 3.2%; P =
      .045); however, the sensitivity and specificity of the threshold value (PPV = 7%)
      were low (58% and 62%, respectively) and the area under the receiver operating
      characteristics curve was only 0.63 (95% confidence interval, 0.52-0.74; P =
      .041). CONCLUSIONS: Dynamic preload indicators are not useful for predicting
      fluid responsiveness in VATS or open thoracic surgery.

PMID- 28504998
TI  - Introduction.

PMID- 28504997
TI  - Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory
      Failure-Practice Variations and Outcomes.
AB  - OBJECTIVE: Describe practice variations in ventilator strategies used for lung
      rest during extracorporeal membrane oxygenation for respiratory failure in
      neonates, and assess the potential impact of various lung rest strategies on the
      duration of extracorporeal membrane oxygenation and the duration of mechanical
      ventilation after decannulation. DATA SOURCES: Retrospective cohort analysis from
      the Extracorporeal Life Support Organization registry database during the years
      2008-2013. STUDY SELECTION: All extracorporeal membrane oxygenation runs for
      infants less than or equal to 30 days of life for pulmonary reasons were
      included. DATA EXTRACTION: Ventilator type and ventilator settings used for lung
      rest at 24 hours after extracorporeal membrane oxygenation initiation were
      obtained. DATA SYNTHESIS: A total of 3,040 cases met inclusion criteria.
      Conventional mechanical ventilation was used for lung rest in 88% of cases and
      high frequency ventilation was used in 12%. In the conventional mechanical
      ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm
      H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High
      frequency ventilation was associated with an increased mean (SEM) hours of
      extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p < 0.001) and
      an increased mean (SEM) hours of mechanical ventilation after decannulation (135
      [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical
      ventilation among survivors. Within the conventional mechanical ventilation
      group, use of higher positive end-expiratory pressure was associated with a
      decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low:
      136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p =
      0.04) but increased duration of mechanical ventilation after decannulation in the
      high positive end-expiratory pressure group compared with low positive end
      expiratory pressure (p = 0.04) among survivors. CONCLUSIONS: Wide practice
      variation exists with regard to ventilator settings used for lung rest during
      neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency
      ventilation when compared with conventional mechanical ventilation and use of low
      positive end-expiratory pressure strategy when compared with mid positive end
      expiratory pressure and high positive end-expiratory pressure strategy is
      associated with longer duration of extracorporeal membrane oxygenation. Further
      research to provide evidence to drive optimization of pulmonary management during
      neonatal respiratory extracorporeal membrane oxygenation is warranted.

PMID- 28504999
TI  - Tumor Microenvironment and Checkpoint Molecules in Primary Cutaneous Diffuse
      Large B-Cell Lymphoma-New Therapeutic Targets.
AB  - Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse
      large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL
      (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples
      of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1,
      and CD33 expression and the cellular composition of the tumor microenvironment,
      focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated
      macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in
      all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10
      cases) were classified as activated B cell like type, with a higher PD-L1 score
      (21.9%) compared with that of the germinal center B cell like type (7.7%). The
      surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+)
      macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+)
      MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable
      degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with
      pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor
      microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield
      the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to
      inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a
      polarization to M2 macrophages, which may contribute to the poor prognosis of
      DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD
      L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this
      aggressive form of cutaneous B-cell lymphoma.

PMID- 28505001
TI  - The Impact of P16 Immunostaining in Reducing Anal Squamous Intraepithelial
      Lesions Indication for Treatment.

PMID- 28505000
TI  - H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign
      and Malignant Giant Cell Tumor of Bone.
AB  - Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor.
      Having recently reported that H3.3 G34W mutations are characteristic of this
      tumor type, we have now investigated the sensitivity and specificity of the anti
      histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors
      including histologic mimics of GCTB to assess its value as a diagnostic marker.
      We also determined the incidence of H3.3 G34 mutations in primary malignant bone
      tumors as assessed by genotype and H3.3 G34W immunostaining. A total of 3163
      tumors were tested. Totally, 213/235 GCTB (90.6%) showed nuclear H3.3 p.G34W
      immunoreactivity. This was not the case for the rare variants, p.G34L, M, and V,
      which occurred most commonly in the small bones of the hands, patella, and the
      axial skeleton. If these sites were excluded from the analysis, H3.3 G34W
      expression was found in 97.8% of GCTB. Malignant bone tumors initially classified
      as osteosarcomas were the only other lesions (n=11) that showed G34W expression.
      Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation
      were not immunoreactive for the antibody. A total of 11/13 of these malignant
      H3.3-mutant tumors exhibited an osteoclast-rich component: when imaging was
      available all but one presented at a subarticular site. We propose that
      subarticular primary malignant bone sarcoma with H3.3 mutations represent true
      malignant GCTB, even in the absence of a benign GCTB component.

PMID- 28505002
TI  - Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal
      Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and
      Highlights MUC5AC as a Strong Prognosticator.
AB  - Recently, immunohistochemistry-based classifications of ampullary carcinomas have
      been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID:
      23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20,
      MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on
      full-faced sections of 136 ampullary carcinoma resections with substantial (>5
      mm) invasion. Immunohistochemistry was correlated with both histologic
      classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on
      >=3/5 observer agreement) and clinical outcome. No prognostic correlation was
      found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative
      cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable
      correlation with histologic subclassification of tubular cases as INT versus PB
      with high specificity but low sensitivity and ambiguous category was large (29%)
      and included also some classical cases. Prognostically, Ang classification
      approached but did not reach statistical significance, even when their large
      "ambiguous" group was eliminated and only tubular cases were analyzed (Ang-INT
      vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT
      subcategory is not clearly defined, only marginally reached prognostic
      significance when tested as MUC1+/CDX2- versus MUC1-/CDX2+ and only by Wilcoxon
      test (P=0.0485) but 31% of the cases were "unclassifiable." The only individual
      marker that was found to have direct and strong correlation with the clinical
      outcome was MUC5AC (not used in the Ang or Chang panels), with statistically
      significant survival differences found with various cutoffs tested (for 20%
      cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly
      stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively),
      as well as Ang's ambiguous and Chang's unclassified cases (P=0.006 and 0.007,
      respectively). In conclusion, the widely used putative lineage markers,
      MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic
      correlation either individually or in combination of Ang and Chang panels. Ang
      panel is helpful as an adjunct in determining the cell lineage with a few
      caveats. MUC5AC proves to be a significant independent prognosticator and should
      be incorporated into evaluation of ampullary carcinomas.

PMID- 28505003
TI  - The Adequacy of Core Biopsy in the Assessment of Smooth Muscle Neoplasms of Soft
      Tissues: Implications for Treatment and Prognosis.
AB  - The grading of soft tissue sarcomas is one of the most important prognostic
      factors and determines patient management. Although grading of most adult-type
      soft tissue sarcomas on biopsies correlates highly with the final grading on the
      excision specimen, it appears less reliable for tumors of smooth muscle. We
      assessed the pathologic findings for smooth muscle neoplasms diagnosed by core
      biopsy at our tertiary sarcoma center, and compared them with those in the
      subsequent excision specimens. A total of 100 patients with leiomyosarcoma first
      diagnosed on core biopsy and with a subsequent excision were identified and the
      accuracy of the biopsy grade determined by comparison with the excision grade.
      Differences in other salient histologic parameters were also noted. A grade
      difference between biopsy and excision specimens of leiomyosarcomas was found in
      68% of cases, with all these cases showing an increase in grade from biopsy to
      excision specimen. Of the 3 parameters used for grading using the French
      Federation of Cancer Centers Sarcoma Group Grading System (FNCLCC), necrosis was
      the score that most commonly differed between biopsy and excision specimen (55%),
      closely followed by the mitotic count (51%). The grading of soft tissue smooth
      muscle tumor biopsies has a lower accuracy compared with other adult soft tissue
      sarcomas and should therefore be taken with caution, particularly as this may be
      an underrepresentation of the true tumor grade.

PMID- 28505005
TI  - Gastric Cancer With Primitive Enterocyte Phenotype: An Aggressive Subgroup of
      Intestinal-type Adenocarcinoma.
AB  - A primitive cell-like gene expression signature is associated with aggressive
      phenotypes of various cancers. We assessed the expression of phenotypic markers
      characterizing primitive cells and its correlation with clinicopathologic and
      molecular characteristics in gastric cancer. Immunohistochemical analysis of a
      panel of primitive phenotypic markers, including embryonic stem cell markers
      (OCT4, NANOG, SALL4, CLDN6, and LIN28) and known oncofetal proteins (AFP and
      GPC3), was performed using tissue microarray on 386 gastric cancers. On the basis
      of the expression profiles, the 386 tumors were clustered into 3 groups: group 1
      (primitive phenotype, n=93): AFP, CLDN6, GPC3, or diffuse SALL4 positive; group 2
      (SALL4-focal, n=56): only focal SALL4 positive; and group 3 (negative, n=237):
      all markers negative. Groups 1 and 2 predominantly consisted of intestinal-type
      adenocarcinoma, including 13 fetal gut-like adenocarcinomas exclusively in group
      1. Group 1 was significantly associated with higher T-stage, presence of vascular
      invasion and nodal metastasis when compared with groups 2 and 3. Group 1 was
      associated with patients' poor prognosis and was an independent risk factor for
      disease-free survival. Group 1 showed frequent TP53 overexpression and little
      association with Epstein-Barr virus or mismatch repair deficiency. Further
      analysis of the Cancer Genome Atlas data set validated our observations and
      revealed that tumors with primitive phenotypes were mostly classified as
      "chromosomal instability" in the Cancer Genome Atlas' molecular classification.
      We identified gastric cancer with primitive enterocyte phenotypes as an
      aggressive subgroup of intestinal-type/chromosomal instability gastric cancer.
      Therapeutic strategies targeting primitive markers, such as GPC3, CLDN6, and
      SALL4, are highly promising.

PMID- 28505004
TI  - A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent
      EWSR1/FUS-ATF1 Fusions.
AB  - Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with
      asbestos exposure and characterized by complex genetic abnormalities, including
      deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32
      has been reported in 2 patients over the age of 60 with peritoneal MM. However,
      the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion
      partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1
      fusions and sought to investigate the prevalence and clinicopathologic features
      associated with this abnormality. As both index cases occurred as intra-abdominal
      tumors in young adults, we searched our files for pleural and peritoneal MM
      occurring in adults younger than age of 40. All cases were tested by fluorescence
      in situ hybridization using custom bacterial artificial chromosomes probes for
      EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was
      performed. A total of 25 MM from patients aged 40 or less were screened, either
      from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40
      y). Two additional ATF1-rearranged tumors were identified at pleural and
      peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total
      of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid
      morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100.
      BAP1 expression was retained in the 3 fusion-positive cases with available
      material, and in 80% (12/15) of the fusion-negative cases. Our results expand the
      spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a
      subgroup of conventional epithelioid MM. Other features of this unique MM subset
      include young age at presentation, lack of asbestos exposure and retained BAP1
      expression.

PMID- 28505006
TI  - Myopericytomatosis: Clinicopathologic Analysis of 11 Cases With Molecular
      Identification of Recurrent PDGFRB Alterations in Myopericytomatosis and
      Myopericytoma.
AB  - Myopericytoma is a benign tumor of concentrically distributed perivascular myoid
      cells. Its molecular basis and relationship with myofibroma/myofibromatosis and
      other pericytic tumors are not fully understood. In our consultation/surgical
      files of over 1000 myopericytic lesions, we identified 11 cases with diffuse
      dermal/subcutaneous involvement by microscopic myopericytomatous nodules, a
      phenomenon we have termed myopericytomatosis. Myopericytomatosis affected mostly
      adults (female:male=8:3; median age, 37 y; range, 9 to 63 y) in the lower
      extremities (foot/ankle, 5; calf, 3; knee, 1; thigh, 1; neck, 1) over months to
      25 years, ranging from 1.5 to 11.0 (median, 6.0) cm in size. Histologically,
      myopericytomatosis displayed diffuse infiltration by innumerable discrete
      myopericytoma/myofibroma-like nodules of bland spindled-to-ovoid cells (smooth
      muscle actin positive), in a mainly perivascular distribution. No mitoses,
      atypia, or necrosis was noted. All patients were treated by surgical excision (1
      patient also received adjuvant radiation), with margins focally positive in 5 of
      6 known cases. Of the 6 cases with follow-up of 0.2 to 13.7 (median, 3.4) years,
      1 recurred locally twice, while 5 cases showed no recurrence. Targeted next
      generation DNA sequencing identified PDGFRB alterations in all cases of
      myopericytomatosis and conventional myopericytoma tested (5 cases each),
      including mutations in 4 cases of myopericytomatosis (N666K in 3; Y562-R565
      deletion in 1 case) and 3 myopericytomas (Y562C, K653E, and splice acceptor
      deletion in 1 case each), as well as low-level PDGFRB amplification in 2 cases of
      myopericytomatosis and 4 myopericytomas. No BRAF, NOTCH, or GLI1 alterations were
      detected. In summary, myopericytomatosis is a rare, strikingly diffuse, but
      apparently benign variant of myopericytoma that typically involves superficial
      soft tissue in adults with innumerable discrete microscopic myopericytomatous
      nodules. The strongly activating PDGFRB mutation N666K is noted in
      myopericytomatosis, but not in conventional myopericytoma, suggesting that PDGFRB
      mutation status may account for their pathogenetic differences. As PDGFRB
      alterations are present in myopericytoma/myopericytomatosis and infantile
      myofibromatosis/myofibroma, these entities indeed lie within a histogenetic
      continuum. Identification of PDGFRB alterations suggests tyrosine kinase
      inhibition as a potential therapeutic strategy in myopericytic neoplasms if
      needed.

PMID- 28505007
TI  - AL Amyloidoma of the Skin/Subcutis: Cutaneous Amyloidosis, Plasma Cell Dyscrasia
      or a Manifestation of Primary Cutaneous Marginal Zone Lymphoma?
AB  - It is unclear whether AL amyloidoma of the skin/subcutis represents a distinct
      entity, an indolent precursor of systemic amyloidosis, or a manifestation of
      cutaneous marginal zone lymphoma (cMZL). We collected 10 cases of cutaneous AL
      amyloidoma in order to better characterize the clinicopathologic features of this
      elusive entity (M:F=4:6; median age: 62.5 y, range: 31 to 82 y). Nine patients
      had a solitary nodule or plaque on the lower extremity (n=7), upper extremity
      (n=1), or chin (n=1). One patient had an AL amyloidoma on the right thigh and a
      second lesion on the right arm showing histopathologic features of cMZL without
      amyloid deposits. Clinical investigations excluded relevant systemic disease in
      all cases. Microscopically, dermal/subcutaneous deposits of amyloid were
      associated with sparse to moderate perivascular infiltrates of lymphocytes and
      monotypic plasma cells (7 with kappa and 3 with lambda light chain restriction).
      The plasma cells expressed CD56 in one of 9 studied cases. One case was
      characterized by a t(14;18)(q32;q21)/IGH-MALT1 translocation. Follow-up was
      available in 8 cases. All remain systemically well after a median time of 86.5
      months (range: 40 to 144 mo). Local recurrence of disease was observed in 3
      patients. A fourth patient presented with a cMZL without amyloid deposits 8 years
      after excision of the cutaneous AL amyloidoma. Although our series is small,
      careful categorization and follow-up of the cases, together with updated
      information in the literature, show clinical and biological links between AL
      amyloidomas of the skin/subcutis and cMZL, suggesting that at least a subset of
      cutaneous AL amyloidoma may represent an unusual manifestation of cMZL (cutaneous
      mucosa-associated lymphoid tissue lymphomas).

PMID- 28505008
TI  - Multinodular and Vacuolating Neuronal Tumor: A Rare Seizure-associated Entity.
AB  - Multinodular and vacuolating neuronal tumor is a recently described seizure
      associated entity with overlapping features of a malformative and neoplastic
      process. We report a case of multinodular and vacuolating neuronal tumor in a 29
      year-old man with a history of recent headaches and complex partial seizures.
      Neuroimaging revealed a nonenhancing, T2 and T2 fluid-attenuated inversion
      recovery hyperintense multinodular lesion in the right temporal lobe. Lesional
      tissue demonstrated well-demarcated nodules of ganglioid cells with vacuolation
      of both the perikarya and the fibrillary neuropil-like background. The ganglioid
      cells showed weak cytoplasmic reactivity for synaptophysin and were nonreactive
      for neurofilament and chromogranin. CD34-positive stellate cells were present
      within the nodules. A 50-gene next-generation sequencing panel did not identify
      any somatic mutations in genomic DNA extracted from the tumor.

PMID- 28505009
TI  - A Novel Grading System Based on Tumor Budding and Cell Nest Size Is a Strong
      Predictor of Patient Outcome in Esophageal Squamous Cell Carcinoma.
AB  - The determination of prognosis in patients with esophageal squamous cell
      carcinoma (ESCC) is primarily based on staging according to the TNM
      classification, whereas conventional grading is of minor clinical importance
      because of its deficiencies in prognostic patient stratification. Recently, a
      novel, highly prognostic grading scheme based on budding activity and cell nest
      size has been proposed for squamous cell carcinoma (SCC) of both pulmonary as
      well as oral origin. In order to investigate the utility and transferability of
      this approach to ESCC, we evaluated budding activity and cell nest size, as well
      as other histomorphologic characteristics, in a cohort of 135 primarily resected
      tumors and correlated the results with clinicopathologic and outcome parameters.
      High budding activity and small cell nest size showed a strong association with
      reduced overall, disease-specific, and disease-free survival (P<0.001,
      respectively) in ESCC. The combination of both markers in a 3-step grading system
      showed excellent prognostic separation of well-differentiated (G1), moderately
      differentiated (G2), and poorly differentiated (G3) carcinomas (P<0.001). The
      hazard ratio for disease-free survival in multivariate analysis under inclusion
      of stage was 2.97 for G2 and 5.42 for G3 ESCC (P<0.001). World Health
      Organization-based grading had no prognostic impact. Taken together, our data
      prove the value of tumor budding and cell nest size as excellent outcome
      predictors in ESCC and validate the utility of a previously established grading
      scheme proposed for oral and pulmonary SCC in this tumor entity. Ultimately,
      these combined efforts may result in a universal grading system for SCC
      regardless of the site of origin.

PMID- 28505010
TI  - Tackling immunomonitoring in gastrointestinal cancer.
AB  - PURPOSE OF REVIEW: The growing awareness that the immune system is a key player
      in the antitumoral response and the excellent clinical results achieved in some
      settings with anti-programmed cell death 1 (PD1)/programmed death ligand 1 (PDL1)
      and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) drugs has led to the
      rise of immunotherapy as a supplement or an alternative to conventional cancer
      treatment. The high costs associated with these therapies, their significant
      toxicity and the need to understand and circumvent immune escape mechanisms raise
      the urgent need for immunological assessment of therapy response. The study of
      the immunological parameters before, during and after treatment is referred to as
      immunomonitoring. This review discusses the current knowledge of immunomonitoring
      markers in gastrointestinal cancers. RECENT FINDINGS: The last decade has seen a
      collaborative effort to standardize the assays performed in clinical trials to
      assess response to immunotherapy. Since then, multiple studies have been
      conducted on blood samples, biopsies and surgical specimens to determine their
      immunological profiles leading to the identification of several immunological
      markers possessing a predictive value of response to treatment. SUMMARY: Future
      research will focus on detangling the predictive value of immune markers in
      different therapeutic models, and also to develop new noninvasive means to
      monitor the immune response of patients. VIDEO ABSTRACT:
      http://links.lww.com/COON/A20.

PMID- 28505011
TI  - In-vitro assessment of the effect of dabigatran on thrombosis of adult and
      neonatal plasma: comparisons using thromboelastography and microscopic
      visualization of fibrin clot structure.
AB  - : Thromboelastography (TEG) is a global assay used for evaluating features of
      clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin
      that has not been studied in neonates using a sophisticated global assay, such as
      TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and
      qualitative characteristics. Our aim was to compare the TEG clotting profile of
      neonatal and adult platelet-poor plasma when exposed to different concentrations
      of dabigatran. We used commercially collected adult pooled plasma and neonatal
      cord blood collected from placentas of healthy full term newborns. Platelet-poor
      plasma was isolated, pooled, and frozen. Prior to experiment, plasma was thawed
      and filtered. A reaction mixture of CaCl2, corn trypsin inhibitor, tissue factor,
      and dabigatran in imidazole buffer was mixed with plasma in a TEG cup. Time to
      clot initiation (R-time), speed of clot strengthening (alpha-angle), and maximum
      clot strength (maximal amplitude) were measured. Scanning electron microscopy was
      performed to evaluate fibrin clot structure. Without dabigatran, there was no
      significant difference in TEG measurements between neonatal and adult samples.
      However, neonatal plasma clotting with dabigatran had slower onset, slower speed,
      and weaker clots that were more porous with thicker fibers, compared with adult
      plasma clotting. Thus, neonatal plasma may be more sensitive to dabigatran as
      assessed by our in-vitro TEG study.

PMID- 28505012
TI  - CORRELATION OF CLINICAL AND STRUCTURAL PROGRESSION WITH VISUAL ACUITY LOSS IN
      MACULAR TELANGIECTASIA TYPE 2: MacTel Project Report No. 6-The MacTel Research
      Group.
AB  - PURPOSE: To evaluate progression of macular telangiectasia Type 2 lesions and
      their correlation with visual acuity. METHODS: An international multicenter
      prospective study with annual examinations including best-corrected visual acuity
      (BCVA), fundus photography, fluorescein angiography, and optical coherence
      tomography images graded centrally. Mixed models were used to estimate
      progression rates, and a generalized linear model to compute the relative risk of
      BCVA loss, loss of ellipsoid zone (EZ) reflectivity, development of pigment
      plaques, or neovascularization. RESULTS: One thousand and fourteen eyes of 507
      participants were followed for 4.2 +/- 1.6 years. Best-corrected visual acuity
      decreased 1.07 +/- 0.05 letters (mean +/- SE) per year. Of all eyes, 15% lost
      >=15 letters after 5 years. Of the eyes without EZ loss, 76% developed a
      noncentral loss. Of the eyes with noncentral loss, 45% progressed to central EZ
      loss. The rate of BCVA loss in eyes with noncentral EZ loss at baseline was
      similar to eyes without EZ loss. The rate of BCVA loss was significantly higher
      in eyes with central EZ loss at baseline (-1.40 +/- 0.14 letters, P < 0.001).
      CONCLUSION: Ellipsoid zone loss is frequently found in macular telangiectasia
      Type 2 and is an important structural component reflecting visual function. Its
      presence in the fovea significantly correlates with worse visual prognosis.

PMID- 28505013
TI  - DISEASE EXPRESSION IN NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION VARIES WITH
      CHOROIDAL THICKNESS.
AB  - PURPOSE: To investigate the relationship between subfoveal choroidal thickness
      and disease manifestation in a series of eyes with nonexudative age-related
      macular degeneration (AMD). METHODS: Retrospective study of eyes with
      nonexudative AMD. The extracellular deposits present, drusen and subretinal
      drusenoid deposits (SDD, pseudodrusen) along with a newly recognized form of
      drusen, pachydrusen, were graded and compared with choroidal thickness as
      determined by optical coherence tomography. Demographic and imaging information
      was evaluated with descriptive statistics and generalized estimating equations.
      RESULTS: There were 94 eyes of 71 patients, who had a mean age of 78.1 years.
      Soft drusen alone were found in 45 eyes (47.9%) and subretinal drusenoid deposit
      with or without drusen in 38 (40.4%). Pachydrusen, which were typically larger
      than 125 MUm, often had an irregular outer contour, showed a scattered
      distribution over the posterior pole and occurred in isolation or in groups of
      only a few drusen were found in 11 (11.7%). The mean subfoveal choroidal
      thickness in the soft drusen group was 227.9 MUm, in the subretinal drusenoid
      deposit group 167.3 MUm, and in the pachydrusen group 419 MUm. The differences
      between the groups were highly significant. CONCLUSION: Extracellular deposits,
      subretinal drusenoid deposits and drusen, which are on either side of the retinal
      pigment epithelium, respectively, are common in nonexudative AMD. A new form of
      drusen presentation could be differentiated from typical soft drusen and was
      associated with thicker choroids. Disease manifestation in nonexudative AMD seems
      to be associated with choroidal thickness. Each of these has potential to lead to
      specific forms of late AMD.

PMID- 28505014
TI  - Validation of a smartphone auscultatory blood pressure kit Accutension XYZ-110 in
      adults according to the ANSI/AAMI/ISO 81060-2: 2013 standard.
AB  - OBJECTIVE: The aim of this study was to validate the accuracy of the Accutension
      XYZ-110 blood pressure (BP) kit according to the American National Standards
      Institute/Association for the Advancement of Medical
      Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO)
      81060-2:2013 standard. PARTICIPANTS AND METHODS: Systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) were measured simultaneously on the same arm
      in 85 Chinese adults (female : male=48 : 37) with a mean age of 43.2 years using
      the mercury sphygmomanometer (two observers) and the Accutension XYZ-110 device
      (one supervisor). The ANSI/AAMI/ISO 81060-2:2013 standard for the validation of
      BP-measuring devices in adults was followed precisely. A total of 255 comparison
      pairs were obtained for analysis. RESULTS: The mean device-observer difference in
      the 255 separate BP data pairs was 2.45+/-2.24 mmHg for SBP and 0.69+/-2.09 mmHg
      for DBP. The data were in accordance with the criterion 1 of the ANSI/AAMI/ISO
      81060-2:2013 standard requirements (<=5+/-8 mmHg). In addition, the mean device
      observer difference of the 85 participants was 2.45+/-1.47 mmHg for SBP and
      0.69+/-1.36 mmHg for DBP. The device accuracy also fulfilled the criterion 2 with
      the SD of less than or equal to 6.47 for SBP and less than or equal to 6.90 mmHg
      for DBP. CONCLUSION: The Accutension XYZ-110 BP kit fulfilled the requirements of
      the ANSI/AAMI/ISO 81060-2:2013 standard, and hence could be recommended for both
      clinical and self/home BP measurement in adults.

PMID- 28505016
TI  - The Contemporary Microbiology of Osteoarticular Infections in Young Children.

PMID- 28505015
TI  - Virologic Response to First-line Efavirenz- or Nevirapine-based Antiretroviral
      Therapy in HIV-infected African Children.
AB  - BACKGROUND: Poorer virologic response to nevirapine- versus efavirenz-based
      antiretroviral therapy (ART) has been reported in adult systematic reviews and
      pediatric studies. METHODS: We compared drug discontinuation and viral load (VL)
      response in ART-naive Ugandan/Zimbabwean children >=3 years of age initiating ART
      with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors
      of suppression <80, <400 and <1000 copies/mL at 36, 48 and 144 weeks were
      identified using multivariable logistic regression with backwards elimination (P
      = 0.1). RESULTS: A total of 445 (53%) children received efavirenz and 391 (47%)
      nevirapine. Children receiving efavirenz were older (median age, 8.6 vs. 7.5
      years nevirapine, P < 0.001) and had higher CD4% (12% vs. 10%, P = 0.05), but
      similar pre-ART VL (P = 0.17). The initial non-nucleoside-reverse-transcriptase
      inhibitor (NNRTI) was permanently discontinued for adverse events in 7 of 445
      (2%) children initiating efavirenz versus 9 of 391 (2%) initiating nevirapine (P
      = 0.46); at switch to second line in 17 versus 23, for tuberculosis in 0 versus
      26, for pregnancy in 6 versus 0 and for other reasons in 15 versus 5. Early (36
      48 weeks) virologic suppression <80 copies/mL was superior with efavirenz,
      particularly in children with higher pre-ART VL (P = 0.0004); longer-term
      suppression was superior with nevirapine in older children (P = 0.05). Early
      suppression was poorer in the youngest and oldest children, regardless of NNRTI
      (P = 0.02); longer-term suppression was poorer in those with higher pre-ART VL
      regardless of NNRTI (P = 0.05). Results were broadly similar for <400 and <1000
      copies/mL. CONCLUSION: Short-term VL suppression favored efavirenz, but long-term
      relative performance was age dependent, with better suppression in older children
      with nevirapine, supporting World Health Organization recommendation that
      nevirapine remains an alternative NNRTI.

PMID- 28505017
TI  - Septic Arthritis due to Streptococcus dysgalactiae Subspecies equisimilis in a
      Healthy School Child.

PMID- 28505018
TI  - The variation of the 5-hydroxytryptamine system between chronic unpredictable
      mild stress rats and chronic fatigue syndrome rats induced by forced treadmill
      running.
AB  - The aim of this study was to observe the variation in the 5-hydroxytryptamine (5
      HT) system between a chronic unpredictable mild stress (CUMS) model and a chronic
      fatigue syndrome (CFS) model. The total distance, the crossing pieces, and
      rearing times in the open-field test of the CUMS group and the CFS group were all
      less than those of the control group to different degrees. The concentrations of
      tryptophan, 5-HT, and 5-HIAA of the CUMS group were obviously lower than those of
      the control group. In the CFS model, the concentrations of tryptophan, 5-HT, and
      5-HIAA were obviously higher than those of the control group. The expressions of
      tryptophan hydroxylase-2 (TPH-2) and 5-HT1A receptor in protein level and mRNA
      level were also different among the three groups. The expressions of TPH-2 and 5
      HT1A were higher in the CFS group than in the CUMS group. The expressions of TPH
      2 and 5-HT1A receptor were lower in the CUMS group than in the control group. We
      can find that in different situations of mood disorders, the variation of 5-HT
      system may also be opposite.

PMID- 28505019
TI  - What'S New in SHOCK, June 2017?

PMID- 28505020
TI  - The Role of Thioredoxin-1 in Suppression Sepsis Through Inhibiting Mitochondrial
      Induced Apoptosis in Spleen.
AB  - Sepsis is a serious public health issue and the leading cause of death in
      critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a
      protein of regulating redox, as well as a modulator of inflammation and
      apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum
      mediated inflammation involved in lung in a model of experimental sepsis.
      However, its effect on mitochondrial-mediated apoptosis in spleen has not been
      reported. We studied whether Trx-1 could prevent spleen cells apoptosis in
      sepsis. In the present study, we showed that the apoptosis in spleen was
      decreased in sepsis induced by cecal ligation and puncture (CLP) in Trx-1
      overexpression transgenic (Tg) mice compared with wild-type mice. Colony forming
      units in the peritoneal cavity and the level of procalcitonin in plasma were
      significantly decreased in Trx-1 Tg mice 12 h after CLP. The expressions of c-jun
      N-terminal kinase, Bax, caspase-9, and caspase-3 were increased in spleen, which
      were suppressed in Trx-1 Tg mice. However, the decreased Bcl-2 expression in
      sepsis was recovered in Trx-1 Tg mice. Our results suggest that overexpression of
      Trx-1 provides protection against sepsis through suppressing mitochondria-induced
      apoptosis pathway in spleen. This study may provide a new target for clinical
      intervention, as well potential strategies for treatment of sepsis.

PMID- 28505021
TI  - Use of a Short-Acting beta1 Blocker During Endotoxemia May Reduce Cerebral Tissue
      Oxygenation if Hemodynamics are Depressed by a Decrease in Heart Rate.
AB  - BACKGROUND: A decrease in heart rate (HR) using a short-acting beta blocker has
      potential benefits in sepsis; however, depression of hemodynamics and reduction
      of cerebral oxygenation may also occur in endotoxemia. METHODS: Seventeen swine
      were allocated to landiolol or control groups. In the landiolol group, the dose
      was sequentially changed from 0 to 40 to 200 MUg kg min, and stopped.
      Hemodynamics, blood variables, and the cerebral tissue oxygenation index (TOI)
      were recorded by near infrared spectroscopy at each dose. Lipopolysaccharide
      (LPS) was then administered continuously at 1 MUg kg h after a 100 MUg bolus
      administration. After 30 and 150 min, as two severity stages of endotoxemia
      (endotoxemia 1 and 2), landiolol was administered as above and measurements were
      made. In the control group, landiolol was not administered, but measurements were
      made. RESULTS: LPS increased HR and landiolol decreased HR, with similar effects
      in each endotoxemia stage. In endotoxemia 1, LPS decreased stroke volume (SV),
      but landiolol restored SV to a value similar to that before endotoxemia, and did
      not decrease cardiac output (CO), even at 200 MUg kg min. In contrast, landiolol
      did not restore SV in endotoxemia 2, resulting in a decrease in CO and mean
      arterial pressure, accompanied with a dose-dependent decrease in TOI.
      CONCLUSIONS: A short-acting beta blocker has various hemodynamic effects in
      endotoxemia. Use of a short-acting beta blocker during endotoxemia may reduce
      cerebral tissue oxygenation if hemodynamics are depressed by a decrease in HR.

PMID- 28505024
TI  - Autonomic Nervous System Pretransplant Malfunction Is a Powerful Predictor of
      Survival After Allogeneic Hematopoietic Cell Transplantation.
AB  - BACKGROUND: Autonomic nervous system function indexed by heart rate variability
      (HRV) has shown prognostic value for mortality in various cardiovascular and
      noncardiovascular diseases including cancer. The purpose of this study was to
      evaluate an association between HRV and outcomes of allogeneic hematopoietic cell
      transplantation (allo-HCT). METHODS: We prospectively measured HRV as a surrogate
      pretransplant marker of autonomic nervous system activity in consecutive allo
      HCTs with hematological diseases. RESULTS: We analyzed 112 allo-HCTs performed
      between July 2011 and July 2013 in our center. Univariate analysis showed that
      increased values of HRV components (low-frequency [LF] and high-frequency [HF]
      spectral component), SD of normal-to-normal RR interval (SDNN), and squares of
      the differences between adjacent normal-to-normal RR intervals (r-MSSD) were
      significantly associated with decreased probability of overall mortality (hazard
      ratio = 0.3 for LF, P < 0.001; hazard ratio = 0.3 for HF, P = 0.001; hazard ratio
      = 0.6 for SDNN, P = 0.004; and hazard ratio = 0.5 for r-MSSD, P = 0.014). Among
      these 4 indicators, the LF-added pretransplantation assessment of mortality,
      hematopoietic cell transplantation-comorbidity index, and disease risk index
      models showed the highest values of DeltaAkaike information criterion (16.5,
      22.2, and 11.4, respectively). When stratified into quartiles of LF groups, 2
      year overall survival was 92.9, 84.5, 59.7, and 33.2%, respectively (P < 0.001).
      LF alone represented a better discriminating variable for the prediction of
      mortality when compared with pretransplantation assessment of mortality,
      hematopoietic cell transplantation-comorbidity index, and disease risk index. In
      addition, from bivariate analyses, decreased LF was an independent and
      significant factor for higher overall mortality in all models. CONCLUSIONS:
      Indicators reflective of autonomic nervous system function might be a powerful
      predictor of survival after allo-HCT.

PMID- 28505025
TI  - A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers
      of Cardiac Viability During Ex Vivo Heart Perfusion.
AB  - BACKGROUND: Organ donation after circulatory death (DCD) is increasingly being
      used as a means of addressing the organ supply/demand mismatch in solid organ
      transplantation. There is reluctance to use DCD hearts, due to an inability to
      precisely identify hearts that have suffered irreversible injury. We investigated
      novel biomarkers and clinically relevant endpoints across a spectrum of warm
      ischemic times, before and during ex vivo heart perfusion (EVHP), to identify
      features associated with a nonviable cardiac phenotype. METHODS: Donor rats
      sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff
      periods (DCD groups). Left ventricular function, histochemical injury, and
      differences in left ventricular gene expression were studied before, and during,
      EVHP. RESULTS: As warm ischemic time exposure increased in DCD groups, fewer
      hearts were functional during EVHP, and ventricular function was increasingly
      impaired. Histochemical assessment identified severely injured hearts during
      EVHP. A novel gene expression signature identified severely injured hearts during
      EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72
      5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be
      useful in identifying high-risk hearts at the point of harvest (Hsp90).
      CONCLUSIONS: We demonstrate that our preclinical model recapitulates the cardio
      respiratory decompensation observed in humans, and that EVHP appears necessary to
      unmask distinguishing features of severely injured DCD hearts. Furthermore, we
      outline a clinically relevant multimodal approach to assessing candidate DCD
      hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in
      severely injured hearts during EVHP, and may also detect injury at the point of
      harvest.

PMID- 28505026
TI  - Combined Heart Lung Transplantation: An Updated Review of the Current Literature.
AB  - Heart lung transplantation is a viable treatment option for patients with many
      end-stage heart and lung pathologies. However, given the complex nature of the
      procedure, it is imperative that patients are selected appropriately, and the
      clinician is aware of the many unique aspects in management of this population.
      This review seeks to describe updated organ selection policies, perioperative and
      postoperative management strategies, monitoring of graft function, and clinical
      outcomes for patients after combined heart-lung transplantation in the current
      era.

PMID- 28505027
TI  - Automated surveillance of healthcare-associated infections: state of the art.
AB  - PURPOSE OF REVIEW: This review describes recent advances in the field of
      automated surveillance of healthcare-associated infections (HAIs), with a focus
      on data sources and the development of semiautomated or fully automated
      algorithms. RECENT FINDINGS: The availability of high-quality data in electronic
      health records and a well-designed information technology (IT) infrastructure to
      access these data are indispensable for successful implementation of automated
      HAI surveillance. Previous studies have demonstrated that reliance on stand-alone
      administrative data is generally unsuited as sole case-finding strategy. Recent
      attempts to combine multiple administrative and clinical data sources in
      algorithms yielded more reliable results. Current surveillance practices are
      mostly limited to single healthcare facilities, but future linkage of multiple
      databases in a network may allow interfacility surveillance. Although prior
      surveillance algorithms were often straightforward decision trees based on
      structured data, recent studies have used a wide variety of techniques for case
      finding, including logistic regression and various machine learning methods. In
      the future, natural language processing may enable the use of unstructured
      narrative data. SUMMARY: Developments in healthcare IT are rapidly changing the
      landscape of HAI surveillance. The electronic availability and incorporation of
      routine care data in surveillance algorithms enhances the reliability, efficiency
      and standardization of surveillance practices.

PMID- 28505028
TI  - Cytomegalovirus disease in hematopoietic stem cell transplant patients: current
      and future therapeutic options.
AB  - PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      has become one of the standard treatment for hematological diseases. Although the
      clinical outcome has improved significantly during the last decades, the
      morbidity and mortality after allo-HSCT are still obstacles to cure. Out of major
      morbidities, opportunistic virus infections such as cytomegalovirus (CMV)
      infection are important complications, in particular in patients who received
      human leukocyte antigen-mismatched HSCT. Here, we aim to summarize information
      about current and future therapeutic options in CMV disease after allo-HSCT.
      RECENT FINDINGS: Recently, not only new drugs but also adoptive T-cell therapy
      are tested in the setting of clinical trials. CMV prophylaxis using letermovir
      significantly reduced the incidence of CMV disease in comparison to placebo in a
      phase III clinical trial. Meanwhile, adoptive T-cell therapies which are fully
      adapted to good manufacturing practice (GMP) conditions are now available. A
      recent multicenter study in Germany showed a promising result using Streptamer
      isolated T-cell therapy. SUMMARY: With the recent development of CMV-targeted
      therapy, treatment strategies of CMV infection would be further sophisticated in
      the near future. VIDEO ABSTRACT: http://links.lww.com/COID/A19.

PMID- 28505029
TI  - Treatment Options for Failed Back Surgery Syndrome Patients With Refractory
      Chronic Pain: An Evidence Based Approach.
AB  - STUDY DESIGN: A significant number of lumbar postsurgical patients continue to
      suffer persistent pain and limited function and are termed to have "Failed back
      surgery syndrome" (FBSS). This review evaluates clinical trial data for the
      treatment of FBSS patients. OBJECTIVE: Using an evidence-based approach to
      evaluate FBSS treatments will assist clinicians in choosing the most effective
      options for FBSS patients. Furthermore, reducing the utilization of less
      effective therapies may result in substantial financial savings for this patient
      population. SUMMARY OF BACKGROUND DATA: Treatments for FBSS may be generally
      categorized as physical therapy and exercise, medications, interventional
      procedures, neuromodulation, and reoperation. Careful review and classification
      of the level of evidence available for each category of treatment for FBSS
      patients will help guide clinical decision-making. METHODS: A literature review
      was performed for FBSS treatments. The publications were arranged hierarchically
      according to the North American Spine Society's guidelines as randomized
      controlled trials (RCTs), prospective studies, retrospective chart, and
      systematic reviews. Book chapters, nonsystematic reviews, and expert opinions
      were excluded. The review focused on studies with at least 20 FBSS patients and 6
      month follow-up. RESULTS: Evidence is weak for medications and reoperation, but
      strong for active exercise and interventional procedures such as adhesiolysis.
      The strongest evidence for long-term treatment is for spinal cord stimulation
      (SCS), showing favorable Level I RCT results compared with conventional medical
      management and reoperation. In addition, high-frequency SCS at 10 kHz has
      demonstrated superiority over traditional, low-frequency SCS for treating low
      back and leg pain in a recent Level I RCT. CONCLUSION: Clinicians may
      increasingly utilize levels of evidence during their evaluation of each FBSS
      patient to render the best therapeutic plan, likely resulting in improved long
      term pain control and reducing costs by avoiding less effective modalities. New
      directions in SCS show promising results for the treatment of FBSS. LEVEL OF
      EVIDENCE: 1.

PMID- 28505030
TI  - Association Between Neurotrophic Factor Expression and Pain-Related Behavior
      Induced by Nucleus Pulposus Applied to Rat Nerve Root.
AB  - STUDY DESIGN: An experimental animal study. OBJECTIVE: To investigate the
      relationship between pain-related behavior and the expression of neurotrophic
      factors in the dorsal root ganglion (DRG) and spinal cord (SC) using a nucleus
      pulposus (NP) rat model. SUMMARY OF BACKGROUND DATA: Neurotrophic factors are
      released from activated glial cells and are associated with pain-related
      behavior. Nerve growth factor (NGF) is a neurotrophic factor that is induced by
      inflammation. METHODS: Rats were divided into an NP group (n = 94) and a sham
      operated group (n = 46). NP harvested from the tail was applied to the left L5
      DRG. Rats in the NP group were then divided into five subgroups: one non
      treatment and four treatment groups. In the treatment groups, a dose of anti-NGF
      antibody or phosphate-buffered saline was administered into the DRG. Behavioral
      testing was performed to investigate the mechanical withdrawal threshold of the
      left hind paw for all groups. Immunohistochemical localization of NGF,
      phosphorylated p38 (p38), and brain-derived neurotrophic factor (BDNF) in the
      DRGs and SCs was performed, and the numbers of immunoreactive (IR) cells were
      counted. RESULTS: The withdrawal threshold in the nontreatment NP group was
      significantly decreased for 35 days, and that of the middle- and high-dose
      treatment rats was significantly higher than the phosphate-buffered saline group
      values. In the DRG, NGF-IR, p38-IR, and BDNF-IR cells were increased for days 21.
      In the SC, BDNF-IR, and p38-IR cells were increased from days 7 to 21.
      CONCLUSION: In the DRG, NGF expression increased, mechanical thresholds were
      reduced, and p38 and BDNF expression was increased in the NP group. p38 and BDNF
      expression was increased in SC neurons during the same period. Inhibition of NGF
      may be a potential treatment for neuropathic pain due to lumbar disc herniation.
      LEVEL OF EVIDENCE: 5.

PMID- 28505031
TI  - Povidone-iodine Solutions Inhibit Cell Migration and Survival of Osteoblasts,
      Fibroblasts, and Myoblasts.
AB  - STUDY DESIGN: In vitro laboratory study. OBJECTIVE: The purpose of this study was
      to identify the effect of dilute povidone-iodine (PVI) solutions on human
      osteoblast, fibroblast and myoblast cells in vitro. SUMMARY OF BACKGROUND DATA:
      Dilute PVI wound lavage has been used successfully in spine and joint
      arthroplasty procedures to prevent postoperative surgical site infection, but
      their biologic effect on host cells is largely unknown. METHODS: Human primary
      osteoblasts, fibroblasts, and myoblasts were expanded in cell culture and
      subjected to various concentrations of PVI (0%, 0.001%, 0.01%, 0.1%, 0.35%, 1%)
      for 3 minutes. To assess the effect of PVI on cell migration, a scratch assay was
      performed, in which a "scratch" was made by a standard pipette tip in a cell
      monolayer following PVI exposure, and time to closure of the scratch was
      evaluated. Cell survival and proliferation was measured 48 hours post-PVI
      exposure using a cell viability and cytotoxicity assay. RESULTS: Closure of the
      scratch defect in all cell monolayers was achieved in <24 hours in untreated
      controls and following exposure to PVI concentrations <0.1%. The scratch defect
      remained open indefinitely following exposure to PVI concentrations of >=0.1%.
      PVI concentrations <0.1% did not have significant effect on survival rates
      compared with control for all cell types. Cells exposed to PVI >= 0.1% had cell
      survival rates of less than 6% (P < 0.05). CONCLUSIONS: Clinically used
      concentration of PVI (0.35%) exerts a pronounced cytotoxic effect on osteoblasts,
      fibroblast, and myoblasts in vitro. Further investigation is required to
      systematically study the effect of PVI on tissue healing in vivo and also
      determine a safe and clinically potent concentration for PVI lavage. LEVEL OF
      EVIDENCE: N/A.

PMID- 28505032
TI  - Do preventive interventions for children of mentally ill parents work? Results of
      a systematic review and meta-analysis.
AB  - PURPOSE OF REVIEW: The transgenerational transmission of mental disorders is one
      of the most significant causes of psychiatric morbidity. Several risk factors for
      children of parents with mental illness (COPMI) have been identified in numerous
      studies and meta-analyses. RECENT FINDINGS: Many interventions have been
      developed for this high-risk group, but data about their efficacy are
      heterogeneous. SUMMARY: The current meta-analysis reports on 96 articles
      including 50 independent samples from randomized controlled trials quantifying
      effects of preventive interventions for COPMI. Random effect models resulted in
      small, though significant Effect Sizes (ES) for programs enhancing the mother
      infant interaction (ES = 0.26) as well as mothers' (ES = 0.33) and children's (ES
      = 0.31) behavior that proved to be stable over the 12-month follow-up, except for
      infants' behavior. Interventions for children/adolescents resulted in significant
      small effects for global psychopathology (ES = 0.13), as well as internalizing
      symptoms (ES = 0.17), and increased significantly over time, with externalizing
      symptoms reaching significance in the follow-up assessments as well (ES = 0.17).
      Interventions addressing parents and children jointly produced overall larger
      effects. Higher study quality was associated with smaller effects. There is a
      dearth of high quality studies that effectively reduce the high risk of COPMI for
      the development of mental disorders.

PMID- 28505033
TI  - Minimally invasive brow lifting techniques.
AB  - PURPOSE OF REVIEW: Aesthetic concerns about upper eyelid and brow position are
      very common in ophthalmic practice. Management of brow descent and devolumization
      requires an approach customized to each patient taking into consideration
      preoperative examination and patient desires. This article will review several
      minimally invasive techniques that can be used to address the needs of patients
      with mild-to-moderate brow ptosis. RECENT FINDINGS: Recent publications describe
      and analyse efficacy of several variations of browpexy techniques. SUMMARY:
      Browpexy techniques provide a minimally invasive way to provide stabilization and
      modest elevation of the lateral brow. They can enhance outcomes of upper eyelid
      surgery in patients with both functional and cosmetic brow ptosis, who desire to
      avoid the cost and morbidity of more formal brow lifting techniques.

PMID- 28505034
TI  - Pediatric corneal transplants.
AB  - PURPOSE OF REVIEW: Pediatric keratoplasty poses unique challenges in clinical and
      surgical management. However, successful transplantation can afford a child
      vision in an otherwise poorly seeing eye. This review will provide an update on
      recent advances in pediatric keratoplasty. RECENT FINDINGS: Although children who
      receive corneal transplants remain at increased risk of rejection, infection, and
      graft dehiscence compared with adult corneal transplant recipients, new surgical
      techniques, and advances in clinical management have led to better outcomes.
      Surgical modifications in penetrating keratoplasty (PKP) offer increased
      stabilization of the delicate pediatric eye. Lamellar surgery, including
      endothelial keratoplasty and deep anterior lamellar keratoplasty, can target
      specific diseased tissue in children with potentially fewer complications. The
      keratoprosthesis can be used successfully in children when the chance of success
      with PKP is especially low. SUMMARY: As our knowledge of prognostic indicators
      and surgical techniques continues to grow, we can offer children safer and more
      targeted surgeries for some of the most challenging corneal diseases. Ultimately,
      successful transplantation with long-term graft survival can be obtained by a
      multidisciplinary approach, with care across ophthalmic specialties, and a
      commitment to long-term follow-up by the patient's family.

PMID- 28505036
TI  - Editorial.

PMID- 28505035
TI  - Invasive fungal sinusitis: treatment of the orbit.
AB  - PURPOSE OF REVIEW: To summarize diagnostic techniques for invasive fungal
      rhinosinusitis and provide a review of treatment options once disease has spread
      to the orbit. RECENT FINDINGS: Improved imaging criteria, polymerase chain
      reaction and other serologic tests show promise in advancing our ability to
      accurately diagnose invasive fungal disease. Currently, there exists three
      treatment options for infected orbital tissue: exenteration, conservative
      debridement and transcutaneous retrobulbar injection of amphotericin B.
      Exenteration, the most frequently reported intervention, has not been proven to
      enhance survival. Conservative debridement and transcutaneous retrobulbar
      injection of amphotericin B are increasingly considered reasonable first-line
      options. SUMMARY: Although investigative tools are improving, invasive fungal
      rhinosinusitis can still pose a diagnostic challenge. No one treatment option for
      the orbit has been proven superior to another. Therefore, it is justified to
      initiate therapy by prioritizing less morbid procedures. If deterioration is
      continually noted, more invasive interventions can then be employed. The
      treatment algorithm established at our institution is provided.

PMID- 28505037
TI  - Getting ready for the first robotic prostatectomy, from basics to real practice.
AB  - PURPOSE OF REVIEW: Robot-assisted radical prostatectomy (RARP) has been embraced
      by urologists and has become a treatment standard in many countries already.
      Learning how to perform a RARP is challenging and has not yet been standardized.
      The current review summarizes the latest concepts regarding the most effective
      way of training for RARP. RECENT FINDINGS: The strategy to learn RARP should
      comprise didactic activities, skills lab training, participating in surgeries and
      mentorship. Skills lab and virtual simulators are valuable tools to develop
      manual abilities and to overcome the initial technical learning curve.
      Participating in surgeries is crucial for familiarization with the robot
      installation, steps of the surgical procedure and is essential for
      troubleshooting. Mentorship improves learning and is the safest way to initiate
      real practice. Innate and individual background variances were suggested to
      influence the learning process; however, there is paucity of robust evidence
      correlating previous surgical experience and, for example videogame playing with
      faster learning of RARP. Structured curricula were proposed to orient the
      training for robotic surgery; currently, only one is focused exclusively on
      urology. SUMMARY: Systematic training is the most effective way to learn and
      surpass the possibly intense learning curve of RARP. Training activities should
      focus on developing cognitive and manual abilities. The existing curricula for
      robotic surgery training still require constant refinement; however, they offer
      good and structured guidance to train for RARP.

PMID- 28505038
TI  - Editorial.

PMID- 28505039
TI  - Patient-reported outcome measures in urology.
AB  - PURPOSE OF REVIEW: Many urologic treatments have similar clinical outcomes,
      necessitating alternative methods to discriminate between options. Patient
      reported outcome measures (PROMs) have become the new standard for evaluating the
      patient experience, and their use has drastically increased over the past decade.
      The purpose of this review is to discuss the status of PROMs in urology,
      highlight commonly used tools and address their future direction. RECENT
      FINDINGS: An increasing number of urology-specific PROMs tools have been
      developed and validated. An increased focus on patient-centered care has provided
      an impetus for their rise in use. Implementation of PROMs has transitioned from
      being primarily descriptive in nature to producing actionable findings. Many
      PROMs are now implemented in daily clinical practice. The future of PROMs will
      involve new instrument development, integration into clinical practice and the
      use of PROMs as performance measures. SUMMARY: PROMs are effective tools for
      characterizing symptom burden and health-related quality of life. With increasing
      clinical implementation, PROMs are playing an increasing role in patients'
      clinical decision-making.

PMID- 28505040
TI  - News and views - June 2017.

PMID- 28505042
TI  - Dissecting Leapfrog: How Well Do Leapfrog Safe Practices Scores Correlate With
      Hospital Compare Ratings and Penalties, and How Much Do They Matter?

PMID- 28505041
TI  - The Potential Return on Public Investment in Detecting Adverse Drug Effects.
AB  - BACKGROUND: Many countries lack fully functional pharmacovigilance programs, and
      public budgets allocated to pharmacovigilance in industrialized countries remain
      low due to resource constraints and competing priorities. OBJECTIVE: Using 3 case
      examples, we sought to estimate the public health and economic benefits resulting
      from public investment in active pharmacovigilance programs to detect adverse
      drug effects. RESEARCH DESIGN: We assessed 3 examples in which early signals of
      safety hazards were not adequately recognized, resulting in continued exposure of
      a large number of patients to these drugs when safer and effective alternative
      treatments were available. The drug examples studied were rofecoxib,
      cerivastatin, and troglitazone. Using an individual patient simulation model and
      the health care system perspective, we estimated the potential costs that could
      have been averted by early systematic detection of safety hazards through the
      implementation of active surveillance programs. RESULTS: We found that earlier
      drug withdrawal made possible by active safety surveillance would most likely
      have resulted in savings in direct medical costs of $773-$884 million for
      rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone
      in the United States through the prevention of adverse events. By contrast, the
      yearly public investment in Food and Drug Administration initiated population
      based pharmacovigilance activities in the United States is about $42.5 million at
      present. CONCLUSION: These examples illustrate a critical and economically
      justifiable role for active adverse effect surveillance in protecting the health
      of the public.

PMID- 28505043
TI  - Response to Letter to the Editor Regarding, Dissecting Leapfrog: How Well Do
      Leapfrog Safe Practices Score Correlate With Hospital Compare Ratings and
      Penalties, and How Much Do They Matter?

PMID- 28505044
TI  - New technological devices for the assessment of systemic inflammation in the
      primary prevention of cardiovascular disease.
AB  - PURPOSE OF REVIEW: The prediction of cardiovascular disease (CVD) events is of
      strategic importance for the primary prevention of one of the big killers in the
      world. Predictive models have a history of decades, but still the desired
      accuracy is not reached by any of the existing models. The inclusion of
      inflammatory factors in the models did not increase their accuracy. In this
      review, we discuss the possible reasons for that failure and we propose a
      paradigm shift. RECENT FINDINGS: Systemic inflammation is a very volatile
      phenomenon. The blood concentration of inflammatory biomarkers may change
      considerably in one individual with a timescale of seconds. Sudden changes in
      environmental conditions can trigger rapid modifications in the inflammatory
      profile of an individual. In routine clinical practice, the blood tests for
      inflammation are carried out at one point in time, not in standard environmental
      conditions, and are therefore inadequate. SUMMARY: We have to direct CVD research
      toward the understanding of the synchronic relationship between external
      environmental conditions and internal physiological reactions. CVD risk
      assessment must be carried out by using continuous real-time monitoring of
      external and internal parameters together, something that may become possible
      with the advent of new technological devices.

PMID- 28505045
TI  - Resistant hypertension in 2017.
AB  - PURPOSE OF REVIEW: Hypertension (HTN) is a ubiquitous condition and cause for
      significant morbidity and mortality. Over 400 000 deaths in the United States are
      related to HTN every year, more than all the Americans who died through all of
      World War II. As many as half the patients with HTN in the United States have
      resistant HTN, a blood pressure greater than 140/90 mmHg despite three
      medications including a diuretic. It appears that the prevalence of HTN and
      resistant HTN is increasing over time. There is a dire need for newer therapies
      that may reduce or eliminate the need for multiple pharmacologic agents, thus
      helping with compliance and reducing the possibility of their adverse events.
      RECENT FINDINGS: The current review summarizes the techniques and results
      reported in recent studies utilizing renal denervation technologies from the
      original Symplicity Trials to newer multipolar electrodes being used for optimal
      denervation. We also report the early experience with noninvasive renal
      denervation. Endovascular carotid body stimulation is also being investigated for
      resistant HTN. Renovascular HTN remains an underlying cause for resistant HTN,
      and revascularization may prove to be an effective treatment for many of these
      patients. SUMMARY: A multipronged approach utilizing lifestyle modification,
      pharmacologic therapy and tailored endovascular treatments may be the algorithm
      to treat the growing cohort of resistant HTN. However, most of the endovascular
      treatments remain to be validated, and renal revascularization for renovascular
      HTN has been set back by recent studies that did not appear to target the real
      renovascular cohort.

PMID- 28505046
TI  - South Asians: why are they at a higher risk for cardiovascular disease?
AB  - PURPOSE OF REVIEW: We comment on the high prevalence of cardiovascular disease
      (CVD) in South Asians (SA). The effect of various risk factors, for example
      biochemical, genetic, lifestyle, socioeconomic factors and psychosocial stress on
      CVD risk is discussed. RECENT FINDINGS: 'Prediabetes' is common in SA, but its
      relationship with coronary artery disease (CAD) is not significant unlike for the
      white population. At the same time, 'prediabetes' in SA is associated with an
      increased risk for cerebrovascular disease (CeVD). The differentiating factor
      could be the high lipids in Europeans and their relationship to CAD. Likewise,
      higher diastolic blood pressure in SA may explain the risk of CeVD. Small, dense,
      low-density lipoprotein (LDL), low high-density lipoprotein-cholesterol (HDL-C)
      concentration and high triglycerides may contribute to atherosclerosis.
      Thrombotic factors such as increased levels of plasminogen activator inhibitor,
      fibrinogen, lipoprotein (a) and homocysteine have been shown to be associated
      with increased CVD. Impaired cerebrovascular autoregulation and sympathovagal
      activity, increased arterial stiffness and endothelial dysfunction may increase
      CVD risk further. In addition, environmental and dietary factors may exaggerate
      the unfavourable cardiovascular profile through genetic factors. SUMMARY: The
      implications of the findings suggest comprehensive screening of SA for CVD.
      Cultural differences should be considered while designing prevention strategies
      specifically targeting barriers for uptake of preventive service.

PMID- 28505047
TI  - Advances in the management of dyslipidemia.
AB  - PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of morbidity and
      mortality in the United States and therapies aimed at lipid modification are
      important for the reduction of cardiovascular risk. There have been many exciting
      advances in lipid management over the recent years. This review discusses these
      recent advances as well as the direction of future studies. RECENT FINDINGS:
      Several recent clinical trials support low-density lipoprotein cholesterol (LDL
      c) reduction beyond maximal statin therapy for improved cardiovascular outcomes.
      Ezetimibe reduced LDL-c beyond maximal statin therapy and was associated with
      improved cardiovascular outcomes for high-risk populations. Further LDL-c
      reduction may also be achieved with proprotein convertase subtilisin/kexin type-9
      (PCSK9) inhibition and a recent trial, Further Cardiovascular Outcomes Research
      with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), was the first to
      show reduction in cardiovascular events for evolocumab. Additional outcome
      studies of monoclonal antibody and RNA-targeted PCSK9 inhibitors are underway.
      Quantitative high-density lipoprotein cholesterol (HDL-c) improvements have
      failed to have clinical impact to date; most recently, cholesteryl ester transfer
      protein inhibitors and apolipoprotein infusions have demonstrated disappointing
      results. There are still ongoing trials in both of these areas, but some newer
      therapies are focusing on HDL functionality and not just the absolute HDL-c
      levels. There are several ongoing studies in triglyceride reduction including
      fatty acid therapy, inhibition of apolipoprotein C-3 or ANGTPL3 and peroxisome
      proliferator-activated receptor-alpha agonists. SUMMARY: Lipid management
      continues to evolve and these advances have the potential to change clinical
      practice in the coming years.

PMID- 28505048
TI  - Long-term Follow-up of Adolescents Treated for Rumination Syndrome in an
      Inpatient Setting.
AB  - OBJECTIVES: Although several studies have demonstrated the short-term benefit of
      the behavioral treatment of rumination syndrome, few have investigated the long
      term outcomes. Studies reporting long-term benefit have involved combined
      pediatric and adult samples or have examined outcomes of patients involved in
      various types of treatment. The purpose of the present study was to examine
      several aspects of long-term outcome in adolescent patients who took part in the
      same intensive, interdisciplinary, inpatient behavioral treatment approach.
      METHODS: Self-report measures were completed by 47 adolescent patients (mean age
      = 15.9) around 1 year or more from discharge from our inpatient program. Measures
      indexed changes in rumination, medical outcomes (eg, use of supplemental
      nutrition), somatic symptoms, and quality of life. RESULTS: Most patients
      reported continued improvement in their rumination over time, with 20% reporting
      cessation of rumination for at least 6 months. The majority of patients no longer
      required supplemental nutrition and reported improvements in somatic symptoms and
      quality of life. Patients who reported greater improvement in rumination also
      reported more significant improvements in their somatic symptoms and quality of
      life. CONCLUSIONS: Intensive behavioral treatment of rumination syndrome leads to
      long-term improvement in rumination as well as other related factors, including
      somatic symptoms and quality of life.

PMID- 28505049
TI  - Perceived Impairment in Sports Participation in Adolescents With Inflammatory
      Bowel Diseases: A Preliminary Examination.
AB  - OBJECTIVE: Physical activity (PA) is important for adolescents with inflammatory
      bowel diseases (IBDs) given the increased risk of developing osteoporosis and the
      increased risk of IBD-related complications among those with IBD and obesity.
      Symptoms such as fatigue, abdominal pain, nausea, and frequent bowel movements
      can interfere with PA. Sports participation is an important source of PA for
      adolescents; however, the extent to which IBD interferes with sports
      participation is unstudied. The present study aimed to examine demographic,
      health-related, physical, and psychosocial correlates of perceived impairment in
      sports participation. METHOD: Seventy-six adolescents (M[SD] = 14.5 [1.8] years,
      45% girls) completed surveys of perceived impairment in sports participation,
      demographics, physical health, and psychosocial health. Physicians rated disease
      activity at enrolment. All participants were diagnosed with IBD for at least a
      year and prescribed a daily oral medication. RESULTS: Nearly half of participants
      reported at least occasional interference in sports participation because of
      their IBD. Active disease (P = 0.014), older age (P = 0.006), and poorer disease
      specific quality of life, and quality of life in physical health and psychosocial
      domains were associated with greater impairment in sports participation in
      bivariate analyses (P < 0.001). In regression analyses, systemic disease-related
      symptoms, body image concerns, and older age emerged as the strongest predictors
      of impairment in sports participation (P < 0.05). CONCLUSIONS: Older adolescents,
      those with greater systemic symptoms, and those with poorer body image may be
      particularly at risk for impairment in sports participation. Addressing barriers
      to sports participation may be a useful strategy in enhancing PA in this patient
      group.

PMID- 28505051
TI  - Nutritional Benefit of Recycling of Bowel Content in an Infant With Short Bowel
      Syndrome.

PMID- 28505050
TI  - Unsedated In-office Transgastrostomy Esophagoscopy to Monitor Therapy in
      Pediatric Esophageal Disease.
AB  - Monitoring therapy in esophageal inflammatory disorders such as eosinophilic
      esophagitis and reflux esophagitis often requires frequent endoscopic evaluation.
      We recently reported the effective use of unsedated in-office transnasal
      esophagoscopy that significantly decreased costs and anesthetic exposure
      associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we
      report a series of pediatric patients with esophagitis with gastrostomy tubes who
      underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting.
      Nine patients (ages 16 months-21 years) tolerated TGE without significant adverse
      events. Biopsy specimens were adequate for evaluation. This series confirms that
      unsedated in-office TGE can be used to successfully obtain mucosal biopsies to
      monitor esophageal inflammatory conditions in children without the use of
      sedation.

PMID- 28505052
TI  - Beyond Efficacy: The Acceptability of Antidepressant Treatment to Patients with
      Inflammatory Bowel Disease.

PMID- 28505053
TI  - Relationship Between Patient Knowledge and Medication Adherence in Inflammatory
      Bowel Disease.

PMID- 28505054
TI  - The Experience of Living With an Ileoanal Pouch: An Interpretative
      Phenomenological Analysis.
AB  - The purpose of this study was to explore the lived experiences of individuals
      living with an ileoanal pouch. A qualitative, phenomenological methodology was
      used to elicit detailed accounts of the impact of living with an ileoanal pouch.
      Ten individuals having an ileoanal pouch, formed as a consequence of ulcerative
      colitis, participated in the study. Semistructured interviews were conducted and
      analyzed using interpretative phenomenological analysis. The following 4 themes
      emerged from the analysis: "a flood of emotions"; "changed body image"; "changes
      in lifestyle"; and "intimacy and sexual relationships." Participants indicated
      that their quality of life after surgery has improved because they were no longer
      suffering from the devastating symptoms of ulcerative colitis. However, a
      considerable number of these participants disclosed that they are still living a
      restricted lifestyle and reported profound changes not only in their physical
      self but also in their social and sexual relationships. By acknowledging these
      experiences, healthcare professionals have the potential to improve the
      psychological, sexual, and social care that these individuals receive.

PMID- 28505055
TI  - GASTRIC INJURY FOLLOWING NASOGASTRIC INTUBATION: A Case Report.

PMID- 28505056
TI  - Relationship Between Psychological Safety and Reporting Nonadherence to a Safety
      Checklist.
AB  - Patient safety checklists are ubiquitous in health care. Nurses bear significant
      responsibility for ensuring checklist adherence. To report nonadherence to a
      checklist and stop an unsafe procedure, a workplace climate of psychological
      safety is needed. Thus, an analysis of organizational data was conducted to
      examine the relationship between psychological safety and reports of nonadherence
      to the central line bundle checklist. Results showed varied perceptions of
      psychological safety but no relationship with nonadherence. Considerations for
      this finding and assessing psychological safety are provided.

PMID- 28505057
TI  - Automated Medication Error Risk Assessment System (Auto-MERAS).
AB  - This study developed the Automated Medical Error Risk Assessment System (Auto
      MERAS), which was incorporated into the electronic health record system. The
      system itself maintained high predictive validity for medication errors at the
      area under the receiver operating characteristic curves of above 0.80 at the time
      of development and validation. This study has found possibilities to predict the
      risk of medication errors that are sensitive to situational and environmental
      risks without additional data entry from nurses.

PMID- 28505058
TI  - Organizational, Regional, and Community Factors Determining Protocol Compliance
      for Patients With Acute Myocardial Infarction.
AB  - This study examined factors determining hospital compliance to Hospital Quality
      Alliance's protocol for patients with myocardial infarction. Using a spatially
      matched sample of 132 Magnet and 264 non-Magnet hospitals, multivariate
      regressions determined significant hospital characteristics associated with
      compliance per Hospital Quality Alliance protocol. Adherence to the Hospital
      Quality Alliance protocols varied widely by hospital characteristics. Registered
      nurse staffing/bed was a key factor determining patient care quality variation.
      Quality of care practices such as protocol compliance should be measured and
      examined separately.

PMID- 28505059
TI  - Creation of an Adult Observation Unit: Improving Outcomes.
AB  - A growing segment of patients in hospitals are considered outpatients, classified
      as observation. These patients neither have the severity of illness nor the
      intensity of service to qualify as inpatients, yet are not well enough to be
      discharged. Hospitals have created observation units to address the clinical
      needs of this growing patient type to provide care in the right setting by
      managing emergency department throughput and utilizing the most efficient
      staffing resources. This article describes the change processes and improvements
      in quality, length of stay, and patient satisfaction, which occurred following
      the implementation of an adult observation unit.

PMID- 28505060
TI  - The APRN Role in Changing Nursing Home Quality: The Missouri Quality Improvement
      Initiative.

PMID- 28505061
TI  - Novel OFD1 frameshift mutation in a Chinese boy with Joubert syndrome: a case
      report and literature review.
AB  - Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of
      ciliopathy with a key diagnostic feature of 'molar tooth sign' in brain MRI. So
      far, over 20 causative genes have been identified, but only one gene (OFD1)
      results in X-linked Joubert syndrome 10 (JBTS10). Six mutations in the OFD1 gene
      have been found to cause JBTS10. In this study, we identified a novel OFD1
      mutation of c.2843_2844 delAA (p.Lys948ArgfsX) in a 3-month-old boy with a 'molar
      tooth sign' and clinical features of JBTS using targeted exome next-generation
      sequencing. The de-novo OFD1 mutation in exon 21 leads to a frameshift mutation
      generating a prematurely truncated protein and is predicted to partly reduce the
      function of the OFD1 protein. Our study expands the genotype-phenotype spectrum
      in JBTS and will have applications in prenatal and early diagnosis of the
      disorder. This is the first report of the OFD1 mutation causing JBTS in a Chinese
      population.

PMID- 28505062
TI  - Relationships between depression and anxiety symptoms scores and blood pressure
      in young adults.
AB  - BACKGROUND: Depression and anxiety are risk factors for cardiovascular disease,
      but their relationship to blood pressure (BP) is less clear. Age-related
      comorbidity and lifestyle factors may confound these relationships. This study
      aimed to assess the relationships among BP, depression and anxiety symptom scores
      and self-reported history of depression in young adults. METHOD: Data on 1014
      participants aged 20 years from the Western Australian Cohort (Raine) Study were
      analyzed for cross-sectional associations between clinic BP and Depression,
      Anxiety, Stress Scale questionnaire scores or a reported history of depression,
      accounting for relevant confounders. RESULTS: Multivariable adjusted analyses
      showed an inverse relationship between SBP with depression (coefficient = -0.10;
      P = 0.012) and anxiety (after excluding two outliers with SBP > 156 mmHg,
      coefficient = -0.13; P = 0.018) scores, independent of sex, BMI, female hormonal
      contraceptive use, alcohol consumption, birth weight and maternal hypertension in
      pregnancy. SBP was 1.6 mmHg lower for 2 SD (16 units) increase in depression
      score. There was an inverse association between self-reported history of
      depression (15.8% of participants) and SBP (coefficient = -1.91; P = 0.023), with
      an interaction with increasing BMI (interaction coefficient = -0.43; P = 0.002)
      enhancing this difference. CONCLUSION: Our findings show that SBP in young adults
      is inversely associated with depression and anxiety scores, independent of a
      range of lifestyle confounders. Despite a positive association between BMI and
      BP, adiposity enhanced the inverse association between self-reported history of
      depression and SBP. These findings contrast with the predisposition of depressed
      participants to cardiovascular disease in later life when decades of unhealthy
      lifestyle changes may dominate.

PMID- 28505063
TI  - Retinal vessel metrics: normative data and their use in systemic hypertension:
      results from the Gutenberg Health Study.
AB  - PURPOSE OF REVIEW: In-vivo measurement of retinal vascular calibers may be used
      as a tool to study the pathophysiology and clinical status of the
      microvasculature of the retina. The aim of this study was to generate normative
      data for retinal vessel parameters, and to evaluate the clinical relevance in
      systemic hypertension. METHODS: Fundus photographs from 4309 participants of the
      Gutenberg Health Study were assessed using the 'retinal vessel analyzer' software
      (IMEDOS). We generated age and sex-specific nomograms in a disease-free
      subpopulation of 890 participants for determining the central retinal arteriolar
      equivalent (CRAE), the central retinal venular equivalent, and the arteriovenous
      ratio (AVR). RESULTS: Women had higher values of CRAE, central retinal venular
      equivalent, and AVR than men, and the decrease in measures with increasing age
      was less steep in women than in men. Systemic hypertension was associated with
      lower values [odds ratio (OR), 95% confidence interval (CI) referring to area
      below the 5% percentile] of AVR (men: OR 2.41, 95% CI 1.669-3.490, P < 0.001;
      women: OR 3.01, 95% CI 2.126-4.268, P < 0.001) and CRAE (men: OR 2.60, 95% CI
      1.563-4.326, P < 0.001, women: OR 3.00, 95% CI 2.004-4.487, P < 0.001). Both
      median CRAE and AVR were lower in participants with uncontrolled hypertension
      (172.28, range 83.05-251.04; and 0.81, range 0.56-1.04) versus those with
      screening-detected hypertension (175.72, range 101.23-222.09, P < 0.001; and
      0.82, range 0.64-1.05, P = 0.001), and versus those with controlled (179.10,
      range 108.19-221.92, P < 0.001; and 0.84, range 0.60-1.08, P < 0.001)
      hypertension. CONCLUSION: The study provides sex and age-specific normative data
      for retinal vasculature. Persons with untreated or insufficiently treated
      hypertension are more likely to have retinal vessel equivalents outside the
      reference range.

PMID- 28505064
TI  - Changes in renal artery dimensions are associated with clinical response to
      radiofrequency renal denervation: a series of studies using quantitative
      angiography and intravascular ultrasound.
AB  - OBJECTIVE: Renal denervation (RDN) can cause focal (notches) and global (spasms)
      changes in renal artery dimensions. We quantified these changes and related them
      to renal norepinephrin tissue content in animals and to blood pressure (BP)
      changes in patients. METHODS: We measured renal artery dimensions pre-RDN and
      post-RDN, utilizing quantitative renal angiography (QRA) in a porcine model and
      in a retrospective patient cohort, and intravascular ultrasound (IVUS) in a
      prospective patient cohort. Focal and global measurements were minimum and mean
      diameter/area/volume with QRA, minimum lumen/vessel/wall area and volume with
      IVUS. BP was assessed with 24-h ambulatory monitoring, norepinephrin content with
      liquid chromatography. RESULTS: In 36 pigs treated unilaterally with RDN,
      norepinephrin content of the treated right kidney was 48.2% of the untreated left
      kidney. QRA measurements following RDN were associated with norepinephrin content
      only of the (treated) right kidney. In the human QRA study (n = 43 patients),
      mean 24-h BP fell by 8/4 and 12/6 mmHg at 1 and 12 months, respectively. More
      pronounced changes in QRA measurements were associated with a more pronounced BP
      drop. In multiple regression models, the change in minimum diameter was
      independently associated with BP changes at 12 months. In the prospective IVUS
      study (n = 17 patients), a larger decrease in minimum lumen/vessel area and
      larger increase of wall area/volume were associated with a larger BP drop.
      CONCLUSION: Focal and global changes in renal arteries following RDN can be
      quantified, using QRA or IVUS, and may serve as markers of a successful
      procedure.

PMID- 28505065
TI  - Arterial reservoir characteristics and central-to-peripheral blood pressure
      amplification in the human upper limb.
AB  - BACKGROUND: Arterial reservoir characteristics are related to blood pressure (BP)
      and independently predict cardiovascular events. It is unknown if arterial
      reservoir characteristics are modified from the central-to-peripheral large
      arteries and whether there is a contributory role to BP amplification. The aim of
      this study was to assess central-to-peripheral changes in arterial reservoir
      characteristics and determine associations with BP. METHODS: Reservoir pressure
      (RP) and excess pressure (XSP) were derived from intra-arterial BP waveforms
      among 51 participants (aged 63 +/- 13 years, 63% men) undergoing clinically
      indicated cardiac angiography. BP waveforms were recorded in the ascending aorta,
      brachial (mid-humerus) and radial (wrist) arteries via catheter pull-back.
      RESULTS: There was no significant difference in RP between arterial sites (54 +/-
      15, 53 +/- 15 and 52 +/- 17 mmHg for the aorta, brachial and radial artery,
      respectively; P = 0.68). Conversely, XSP increased stepwise from the aorta to the
      brachial and radial arteries (24 +/- 11, 42 +/- 14 and 53 +/- 16 mmHg; P <
      0.001), as did SBP (134 +/- 18, 141 +/- 16 and 146 +/- 19 mmHg; P = 0.004). There
      were highly significant associations between RP and SBP at all arterial sites (r
      = 0.821, 0.649 and 0.708; P < 0.001 for all), but the strength of associations
      between peak XSP and SBP increased significantly from the aorta to the radial
      artery (r = 0.121 and 0.508; z = 3.04; P = 0.004). CONCLUSION: Arterial reservoir
      characteristics are modified through the large arteries of the upper limb.
      Although RP remains relatively constant, XSP increases significantly and is
      highly related to BP (SBP and pulse pressure) amplification. These data provide a
      new understanding on arterial reservoir characteristics and large-artery BP
      physiology.

PMID- 28505066
TI  - Routine urinary detection of antihypertensive drugs for systematic evaluation of
      adherence to treatment in hypertensive patients.
AB  - BACKGROUND: Nonadherence to antihypertensive therapy is an important cause of
      poor blood pressure control. However, to date, few effective and accurate tools
      exist to routinely evaluate drug nonadherence. METHODS: In this observational
      study, performed under conditions of routine clinical practice, we included 174
      patients (aged 67 +/- 11 years) with treated essential hypertension who attended
      the outpatient hypertension clinic of a university hospital. Adherence to
      antihypertensive treatment was measured by using ultraperformance liquid
      chromatography-tandem mass spectrometry in spot urine at the time of clinical
      appointment and blood pressure measurement. Patients were also asked to report
      their adherence using a validated questionnaire (four-item Morisky Medication
      Adherence Scale). RESULTS: The prevalence of directly measured nonadherence by
      urine drug detection was approximately 10%. Compared with adherent patients,
      those who did not adhere to their treatment (n = 15) had a higher number of
      antihypertensive pills and drugs (P = 0.02), cotreatment with cardiovascular
      drugs (P < 0.05), and total concurrent medications and pills (P < 0.01). After
      adjustment for age, SBP and DBP were higher in nonadherent than adherent group
      (SBP: 146 +/- 18 vs. 131 +/- 14, respectively, P < 0.01; and DBP: 77 +/- 15 vs.
      73 +/- 9, respectively, P < 0.01). There was no significant association between
      four-item Morisky Medication Adherence Scale score and directly measured
      nonadherence. A longitudinal analysis, performed in a subpopulation of 105
      patients after a median follow-up of 11 months, showed that the adherence status
      remained unchanged in 88% of patients. CONCLUSION: These results indicate a good
      adherence to antihypertensive drugs in patients attending the outpatient clinics
      of a university hospital. They suggest that urine detection of antihypertensive
      drugs by ultraperformance liquid chromatography-tandem mass spectrometry is an
      accurate and practical tool for directly monitoring adherence. This direct
      information is not overlapping with self-report questionnaire.

PMID- 28505067
TI  - Risk Assessment of Florists Exposed to Pesticide Residues through Handling of
      Flowers and Preparing Bouquets.
AB  - Flowers are frequently treated with pesticides and, as a result, florists
      handling daily a large number of flowers can be exposed to pesticide residues. A
      study was conducted among twenty volunteer florists located in Namur Province and
      in the Brussels Capital Region of Belgium in order to assess their potential
      dermal exposure to dislodgeable pesticide residues transferred from flowers to
      hands. Two pairs of cotton gloves were worn during two consecutive half days
      while handling flowers and preparing bouquets (from min 2 h to max 3 h/day). The
      residual pesticide deposits on the glove samples were extracted with a multi
      residue Quick Easy Cheap Effective Rugged Safe (QuEChERS) method and analyzed by
      a combination of gas and liquid chromatography tandem mass spectrometry (GC-MS/MS
      and LC-MS/MS) by an accredited laboratory. A total of 111 active substances
      (mainly insecticides and fungicides) were detected, with an average of 37 active
      substances per sample and a total concentration per glove sample of 22.22 mg/kg.
      Several predictive levels of contamination were considered to assess the risk.
      The potential dermal exposures (PDE) of florists were estimated at the average,
      for different percentiles, and at the maximum concentration of residues in
      samples. At the PDE P90 and at the PDEMAX (or worst case) values, three and five
      active substances respectively exceed the Acceptable Operator Exposure Level
      (AOEL), indicating risk situations. For the systemic exposure (SE), one active
      substance (clofentezine) exceeds the AOEL at the P90 predictive level. In the
      worst case, SEMAX (at the maximum concentrations), four active substances
      (clofentezine, famoxadone, methiocarb, and pyridaben) exceed their respective
      AOEL values. Among the 14 most frequently detected active substances, two have
      SEMAX values exceeding the AOEL. Exposure could be particularly critical for
      clofentezine with an SEMAX value four times higher than the AOEL (393%). The
      exposure of florists appeared to be an example of a unique professional situation
      in which workers are exposed regularly to both a very high number of toxic
      chemicals and rather high concentration levels. Therefore the priority should be
      to raise the level of awareness among the florists who must change their habits
      and practices if they want to minimize their exposure.

PMID- 28505068
TI  - A New Method for the Fast Analysis of Trihalomethanes in Tap and Recycled Waters
      Using Headspace Gas Chromatography with Micro-Electron Capture Detection.
AB  - Chemical disinfection of water supplies brings significant public health benefits
      by reducing microbial contamination. The process can however, result in the
      formation of toxic compounds through interactions between disinfectants and
      organic material in the source water. These new compounds are termed disinfection
      by-products (DBPs). The most common are the trihalomethanes (THMs) such as
      trichloromethane (chloroform), dichlorobromomethane, chlorodibromomethane and
      tribromomethane (bromoform); these are commonly reported as a single value for
      total trihalomethanes (TTHMs). Analysis of DBPs is commonly performed via time-
      and solvent-intensive sample preparation techniques such as liquid-liquid and
      solid phase extraction. In this study, a method using headspace gas
      chromatography with micro-electron capture detection was developed and applied
      for the analysis of THMs in drinking and recycled waters from across Melbourne
      (Victoria, Australia). The method allowed almost complete removal of the sample
      preparation step whilst maintaining trace level detection limits (>1 ppb). All
      drinking water samples had TTHM concentrations below the Australian regulatory
      limit of 250 ug/L but some were above the U.S. EPA limit of 60 ug/L. The highest
      TTHM concentration was 67.2 ug/L and lowest 22.9 ug/L. For recycled water,
      samples taken directly from treatment plants held significantly higher
      concentrations (153.2 ug/L TTHM) compared to samples from final use locations
      (4.9-9.3 ug/L).

PMID- 28505070
TI  - Characterization of Fine Metal Particles Derived from Shredded WEEE Using a
      Hyperspectral Image System: Preliminary Results.
AB  - Waste of electric and electronic equipment (WEEE) is the fastest-growing waste
      stream in Europe. The large amount of electric and electronic products introduced
      every year in the market makes WEEE disposal a relevant problem. On the other
      hand, the high abundance of key metals included in WEEE has increased the
      industrial interest in WEEE recycling. However, the high variability of materials
      used to produce electric and electronic equipment makes key metals' recovery a
      complex task: the separation process requires flexible systems, which are not
      currently implemented in recycling plants. In this context, hyperspectral sensors
      and imaging systems represent a suitable technology to improve WEEE recycling
      rates and the quality of the output products. This work introduces the
      preliminary tests using a hyperspectral system, integrated in an automatic WEEE
      recycling pilot plant, for the characterization of mixtures of fine particles
      derived from WEEE shredding. Several combinations of classification algorithms
      and techniques for signal enhancement of reflectance spectra were implemented and
      compared. The methodology introduced in this study has shown characterization
      accuracies greater than 95%.

PMID- 28505069
TI  - B-Vitamin Intake from Diet and Supplements and Breast Cancer Risk in Middle-Aged
      Women: Results from the Prospective NutriNet-Sante Cohort.
AB  - Experimental studies suggest a protective effect of B-vitamins on breast cancer
      risk, potentially modulated by alcohol intake. However, epidemiological studies
      are limited, especially regarding non-folate B-vitamins. Furthermore, few studies
      included quantitative assessment of supplemental intake. This prospective study
      aimed to investigate the associations between intakes of B-vitamins (dietary,
      supplemental, total) and breast cancer risk. 27,853 women aged >=45 years from
      the NutriNet-Sante cohort (2009-2016) were included, with a median follow-up time
      of 4.2 years. Dietary data were collected using repeated 24 h records. A specific
      questionnaire assessed dietary supplement use over a 12-month period. A
      composition database of 8000 supplements was developed. Associations were
      characterized by multivariable Cox models, and 462 incident breast cancers were
      diagnosed. Dietary (HRQ4vs.Q1 = 0.74 (0.55, 0.99), P-trend = 0.05), supplemental
      (HRQ4vs.Q1 = 0.61 (0.38, 0.98), P-trend = 0.05), and total (HRQ4vs.Q1 = 0.67
      (0.50, 0.91), P-trend = 0.01) pyridoxine intakes were inversely associated with
      breast cancer risk. Total thiamin intake was borderline inversely associated with
      breast cancer risk (HRper 1-unit increment = 0.78 (0.61, 1.00), P = 0.05).
      Statistically significant interactions between alcohol consumption and B-vitamin
      (thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folate, and
      cobalamin) supplemental intake were observed, the latter being inversely
      associated with breast cancer risk in non-to-low alcohol drinkers but not in
      higher drinkers. This large prospective study, including quantitative assessment
      of supplemental intake, suggests a potential protective effect of pyridoxine and
      thiamin on breast cancer risk in middle-aged women.

PMID- 28505072
TI  - A Feasibility Study of Personalized Prescription Schemes for Glioblastoma
      Patients Using a Proliferation and Invasion Glioma Model.
AB  - Purpose: This study investigates the feasibility of personalizing radiotherapy
      prescription schemes (treatment margins and fractional doses) for glioblastoma
      (GBM) patients and their potential benefits using a proliferation and invasion
      (PI) glioma model on phantoms. Methods and Materials: We propose a strategy to
      personalize radiotherapy prescription schemes by simulating the proliferation and
      invasion of the tumor in 2D according to the PI glioma model. We demonstrate the
      strategy and its potential benefits by presenting virtual cases, where the
      standard and personalized prescriptions were applied to the tumor. Standard
      prescription was assumed to deliver 46 Gy in 23 fractions to the initial, gross
      tumor volume (GTV1) plus a 2 cm margin and an additional 14 Gy in 7 fractions to
      the boost GTV2 plus a 2 cm margin. The virtual cases include the tumors with a
      moving velocity of 0.029 (slow-move), 0.079 (average-move), and 0.13 (fast-move)
      mm/day for the gross tumor volume (GTV) with a radius of 1 (small) and 2 (large)
      cm. For each tumor size and velocity, the margin around GTV1 and GTV2 was varied
      between 0-6 cm and 1-3 cm, respectively. Equivalent uniform dose (EUD) to normal
      brain was constrained to the EUD value obtained by using the standard
      prescription. Various linear dose policies, where the fractional dose is linearly
      decreasing, constant, or increasing, were investigated to estimate the temporal
      effect of the radiation dose on tumor cell-kills. The goal was to find the
      combination of margins for GTV1 and GTV2 and a linear dose policy, which minimize
      the tumor cell-surviving fraction (SF) under a normal tissue constraint. The
      efficacy of a personalized prescription was evaluated by tumor EUD and the
      estimated survival time. Results: The personalized prescription for the slow-move
      tumors was to use 3.0-3.5 cm margins for GTV1, and a 1.5 cm margin for GTV2. For
      the average- and fast-move tumors, it was optimal to use a 6.0 cm margin for GTV1
      and then 1.5-3.0 cm margins for GTV2, suggesting a course of whole brain therapy
      followed by a boost to a smaller volume. It was more effective to deliver the
      boost sequentially using a linearly decreasing fractional dose for all tumors.
      Personalized prescriptions led to surviving fractions of 0.001-0.465% compared to
      the standard prescription, and increased the tumor EUDs by 25.3-49.3% and
      estimated survival times by 7.6-22.2 months. Conclusions: Personalizing treatment
      margins based on the measured proliferative capacity of GBM tumor cells can
      potentially lead to significant improvements in tumor cell kill and related
      clinical outcomes.

PMID- 28505073
TI  - Anti-Pigmentary Effect of (-)-4-Hydroxysattabacin from the Marine-Derived
      Bacterium Bacillus sp.
AB  - Bioactivity-guided isolation of a crude extract from a culture broth of Bacillus
      sp. has led to the isolation of (-)-4-hydroxysattabacin (1). The inhibitory
      effect of (-)-4-hydroxysattabacin (1) was investigated on melanogenesis in the
      murine melanoma cell line, B16F10, and human melanoma cell line, MNT-1, as well
      as a pigmented 3D-human skin model. (-)-4-Hydroxysattabacin treatment decreased
      melanin contents in a dose-dependent manner in alpha-melanocyte stimulating
      hormone (alpha-MSH)-stimulated B16F10 cells. Quantitative real time PCR (qRT-PCR)
      demonstrated that treatment with (-)-4-hydroxysattabacin down-regulated several
      melanogenic genes, including tyrosinase, tyrosinase-related protein 1 (TRP-1),
      and tyrosinase-related protein 2 (TRP-2) while their enzymatic activities were
      unaffected. The anti-melanogenic effects of (-)-4-hydroxysattabacin were further
      demonstrated in a pigmented 3D human epidermal skin model, MelanodermTM, and
      manifested as whitening and regression of melanocyte activation in the tissue.

PMID- 28505076
TI  - Comprehensive and Highly Accurate Measurements of Crane Runways, Profiles and
      Fastenings.
AB  - The process of surveying crane runways has been continually refined due to the
      competitive situation, modern surveying instruments, additional sensors,
      accessories and evaluation procedures. Guidelines, such as the International
      Organization for Standardization (ISO) 12488-1, define target values that must be
      determined by survey. For a crane runway these are for example the span, the
      position and height of the rails. The process has to be objective and
      reproducible. However, common processes of surveying crane runways do not meet
      these requirements sufficiently. The evaluation of the protocols, ideally by an
      expert, requires many years of experience. Additionally, the recording of crucial
      parameters, e.g., the wear of the rail, or the condition of the rail fastening
      and rail joints, is not regulated and for that reason are often not considered
      during the measurement. To solve this deficit the Advanced Rail Track Inspection
      System (ARTIS) was developed. ARTIS is used to measure the 3D position of crane
      rails, the cross-section of the crane rails, joints and, for the first time, the
      (crane-rail) fastenings. The system consists of a monitoring vehicle and an
      external tracking sensor. It makes kinematic observations with the tracking
      sensor from outside the rail run, e.g., the floor of an overhead crane runway,
      possible. In this paper we present stages of the development process of ARTIS,
      new target values, calibration of sensors and results of a test measurement.

PMID- 28505071
TI  - MYC-Master Regulator of the Cancer Epigenome and Transcriptome.
AB  - Overexpression of MYC is a hallmark of many human cancers. The MYC oncogene has
      long been thought to execute its neoplastic functions by acting as a classic
      transcription factor, deregulating the expression of a large number of specific
      target genes. However, MYC's influence on many of these target genes is rather
      modest and there is little overlap between MYC regulated genes in different cell
      types, leaving many mechanistic questions unanswered. Recent advances in the
      field challenge the dogma further, revealing a role for MYC that extends beyond
      the traditional concept of a sequence-specific transcription factor. In this
      article, we review MYC's function as a regulator of the cancer epigenome and
      transcriptome. We outline our current understanding of how MYC regulates
      chromatin structure in both a site-specific and genome-wide fashion, and
      highlight the implications for therapeutic strategies for cancers with high MYC
      expression.

PMID- 28505075
TI  - Knowledge about Iodine in Pregnant and Lactating Women in the Oslo Area, Norway.
AB  - BACKGROUND: Lack of knowledge about iodine may be a risk factor for iodine
      deficiency in pregnant and lactating women. The aim of this study was to assess
      knowledge about iodine and predictors of iodine knowledge scores among pregnant
      and lactating women. The study also examined whether iodine knowledge scores were
      associated with iodine status. METHODS: A cross-sectional study was performed on
      804 pregnant women and 175 lactating women from 18 to 44 years of age in 2016 in
      the Oslo area, Norway. Knowledge about iodine was collected through a self
      administered, paper-based questionnaire. Iodine concentrations in urine and
      breast milk were measured using an inductively coupled plasma mass spectrometer
      (ICPMS). RESULTS: 74% of the pregnant women and 55% of the lactating women
      achieved none to low iodine knowledge scores. Higher educated pregnant women and
      those who had received information about iodine had significantly higher
      knowledge scores. In lactating women, increased age was associated with higher
      knowledge scores. Knowledge scores were not associated with participants' iodine
      status. CONCLUSION: This study revealed a lack of knowledge about the importance
      of iodine in pregnant and lactating women, as well as about the most important
      dietary sources. Public education initiatives are required to increase the
      awareness about iodine in these population groups.

PMID- 28505074
TI  - NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement
      Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a
      High-Fat Diet.
AB  - Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of
      cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia,
      inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to
      atherosclerotic lesions. In the present study, the impact of a natural dietary
      supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid
      and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of
      action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice
      were simultaneously treated with a daily oral administration (os) of the NDS.
      NAFLD and atherogenic lesions in aorta and carotid artery (histological
      analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic
      angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma
      angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis,
      aortic lesions or carotid artery thickening was not observed. PCR array showed
      upregulation of some genes involved in lipid metabolism and anti-inflammatory
      activity (Cpt2, Ifng) and downregulation of some genes involved in pro
      inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT,
      AT1R mRNA and ANG II plasma levels were significantly lower with respect to the
      untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the
      untreated animals. Altogether, these results suggest that NDS prevents NAFLD and
      atherogenesis by modulating the expression of different genes involved in NAFLD
      and avoiding RAS imbalance.

PMID- 28505078
TI  - Intra-Minute Cloud Passing Forecasting Based on a Low Cost IoT Sensor-A Solution
      for Smoothing the Output Power of PV Power Plants.
AB  - Clouds moving at a high speed in front of the Sun can cause step changes in the
      output power of photovoltaic (PV) power plants, which can lead to voltage
      fluctuations and stability problems in the connected electricity networks. These
      effects can be reduced effectively by proper short-term cloud passing forecasting
      and suitable PV power plant output power control. This paper proposes a low-cost
      Internet of Things (IoT)-based solution for intra-minute cloud passing
      forecasting. The hardware consists of a Raspberry PI Model B 3 with a WiFi
      connection and an OmniVision OV5647 sensor with a mounted wide-angle lens, a
      circular polarizing (CPL) filter and a natural density (ND) filter. The
      completely new algorithm for cloud passing forecasting uses the green and blue
      colors in the photo to determine the position of the Sun, to recognize the
      clouds, and to predict their movement. The image processing is performed in
      several stages, considering selectively only a small part of the photo relevant
      to the movement of the clouds in the vicinity of the Sun in the next minute. The
      proposed algorithm is compact, fast and suitable for implementation on low cost
      processors with low computation power. The speed of the cloud parts closest to
      the Sun is used to predict when the clouds will cover the Sun. WiFi communication
      is used to transmit this data to the PV power plant control system in order to
      decrease the output power slowly and smoothly.

PMID- 28505079
TI  - Melatonin Secretion Is Increased in Children with Severe Traumatic Brain Injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and
      disability in children. Oxidative stress plays a significant role in brain damage
      and melatonin exhibits both direct and indirect antioxidant effects. The primary
      aim of the present study was to evaluate serum melatonin levels in children with
      severe TBI in comparison to critically ill children admitted to the Pediatric
      Intensive Care Unit for conditions other than TBI. METHODS: Twenty-four children
      were evaluated, equally divided into severe TBI and no-TBI. Blood samples for
      serum melatonin analysis were collected at 22:00, 01:00, 03:00, 05:00, 08:00, and
      12:00. RESULTS: Mean serum melatonin peaks in children of the TBI group were
      higher compared to the values of no-TBI critically ill children (495 +/- 102 vs.
      294 +/- 119 pg/mL, p = 0.0002). Furthermore, the difference was even more
      significant in comparison to values reported in literature for healthy age
      matched children (495 +/- 102 vs. 197 +/- 71 pg/mL, p < 0.0001). CONCLUSION: This
      study has shown that endogenous serum melatonin levels dramatically increase in
      children after severe TBI. This elevation is likely to represent a response to
      oxidative stress and/or inflammation due to severe head injury.

PMID- 28505077
TI  - Determination of Genes Related to Uveitis by Utilization of the Random Walk with
      Restart Algorithm on a Protein-Protein Interaction Network.
AB  - Uveitis, defined as inflammation of the uveal tract, may cause blindness in both
      young and middle-aged people. Approximately 10-15% of blindness in the West is
      caused by uveitis. Therefore, a comprehensive investigation to determine the
      disease pathogenesis is urgent, as it will thus be possible to design effective
      treatments. Identification of the disease genes that cause uveitis is an
      important requirement to achieve this goal. To begin to answer this question, in
      this study, a computational method was proposed to identify novel uveitis-related
      genes. This method was executed on a large protein-protein interaction network
      and employed a popular ranking algorithm, the Random Walk with Restart (RWR)
      algorithm. To improve the utility of the method, a permutation test and a
      procedure for selecting core genes were added, which helped to exclude false
      discoveries and select the most important candidate genes. The five-fold cross
      validation was adopted to evaluate the method, yielding the average F1-measure of
      0.189. In addition, we compared our method with a classic GBA-based method to
      further indicate its utility. Based on our method, 56 putative genes were chosen
      for further assessment. We have determined that several of these genes (e.g.,
      CCL4, Jun, and MMP9) are likely to be important for the pathogenesis of uveitis.

PMID- 28505081
TI  - Isolation of Rice Bran Lectins and Characterization of Their Unique Behavior in
      Caco-2 Cells.
AB  - Rice bran lectins, named as RBA1 and RBA2, were isolated from Oryza sativa in two
      chromatography steps: affinity chromatography and cation-exchange chromatography.
      RBA1 was found to be composed of a covalently linked heterodimer of 20- and 12
      kDa subunits, and RBA2 was a noncovalently linked dimer of 12-kDa subunits. Both
      RBA1 and RBA2 bound to desialylated complex glycoproteins such as fetuin, alpha1
      acid glycoprotein, and transferrin, and agalactosylated complex glycoproteins
      such as agalacto fetuin, agalacto-alpha1-acid glycoprotein, and agalacto
      transferrin, in addition to chitooligosacchrides. RBAs were heat stable up to 80 
      degrees C and stable at pH 4-10. RBA1 increased the transport of the fluorescent
      marker, rhodamine 123, which is known to be transported via the P-glycoprotein
      mediated efflux pathway across human intestinal Caco-2 cell monolayers.
      Furthermore, RBA1 itself was transported to the basolateral side of the
      monolayers via an endocytotic pathway.

PMID- 28505080
TI  - First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and
      Wound Microenvironment Assessment.
AB  - Fingertip response to trauma represents a fascinating example of tissue
      regeneration. Regeneration derives from proliferative mesenchymal cells
      (blastema) that subsequently differentiate into soft and skeletal tissues.
      Clinically, conservative treatment of the amputated fingertip under occlusive
      dressing can shift the response to tissue loss from a wound repair process
      towards regeneration. When analyzing by Immunoassay the wound exudate from
      occlusive dressings, the concentrations of brain-derived neurotrophic factor
      (BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates
      than in burn wounds (used as controls for wound repair versus regeneration).
      Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor
      (PDGF) were highly expressed in both samples in comparable levels. In our study,
      pro-inflammatory cytokines were relatively higher expressed in regenerative
      fingertips than in the burn wound exudates while chemokines were present in lower
      levels. Functional, vascular and mechanical properties of the regenerated
      fingertips were analyzed three months after trauma and the data were compared to
      the corresponding fingertip on the collateral uninjured side. While sensory
      recovery and morphology (pulp thickness and texture) were similar to uninjured
      sides, mechanical parameters (elasticity, vascularization) were increased in the
      regenerated fingertips. Further studies should be done to clarify the importance
      of inflammatory cells, immunity and growth factors in determining the outcome of
      the regenerative process and its influence on the clinical outcome.

PMID- 28505082
TI  - Supervised Clustering of Adipokines and Hormonal Receptors Predict Prognosis in a
      Population of Obese Women with Type 1 Endometrial Cancer.
AB  - Obesity is a major risk factor for endometrial cancer (EC). Yet, its impact on
      prognosis is controversial. Obesity is associated with metabolic and hormonal
      dysregulation as well as adipokines increase. The aim of this study was to
      characterize the expression of biological factors related to obesity within the
      tumor and evaluate their impact on prognosis. One hundred and thirty-six
      patients, including 55 obese patients, with endometrioid type I EC operated by
      total hysterectomy were included in this retrospective study conducted in a
      Tertiary teaching hospital between 2000 and 2013. Immunohistochemistry (IHC)
      study was performed on type I EC tumor samples using five adipokines (SPARC, RBP4
      (Retinol Binding Protein 4), adiponectin, TNF alpha, IL-6) and hormonal receptors
      (estrogen receptor and progesterone receptor). Supervised clustering of
      immunohistochemical markers was performed to identify clusters that could be
      associated with prognostic groups. The prognosis of the obese population was not
      different from the prognosis of the general population. Adipokine expression
      within tumors was not different in these two populations. In obese population, we
      found three clusters where co-expression was associated with a recurrence group
      in comparison with a non-recurrence group and four clusters where co-expression
      was associated with the high risk FIGO (International Federation of Gynecology
      and Obstetrics) stage I group in comparison of low risk FIGO stage I group. While
      obesity does not appear as a prognostic factor in endometrioid type I EC, the co
      expression of biological factors in IHC on hysterectomy specimens allowed to
      distinguish two prognostic groups in obese population.

PMID- 28505083
TI  - Family Planning and the Samburu: A Qualitative Study Exploring the Thoughts of
      Men on a Population Health and Environment Programme in Rural Kenya.
AB  - Population Health and Environment (PHE) strategies are argued to improve
      ecosystem and human health by addressing family size and its effects on natural
      resource use, food security, and reproductive health. This study investigates
      men's views on a PHE family planning (FP) programme delivered among the pastoral
      Samburu tribe in rural northern Kenya. Three focus group discussions and nine
      semi-structured interviews were conducted with 27 Samburu men. These discussions
      revealed support for environmentally-sensitised family planning promotion. Men
      highlighted their dependency on natural resources and challenges faced in
      providing for large families and maintaining livestock during drought. These
      practices were said to lead to natural resource exhaustion, environmental
      degradation, and wildlife dispersal, undermining key economic benefits of
      environmental and wildlife conservation. Relating family size to the environment
      is a compelling strategy to improve support for FP among Samburu men. Kenyan
      policy-makers should consider integrating community-based PHE strategies among
      underserved pastoral groups living in fragile ecosystems.

PMID- 28505085
TI  - Sparsity Adaptive Matching Pursuit Detection Algorithm Based on Compressed
      Sensing for Radar Signals.
AB  - In this paper, the application of the emerging compressed sensing (CS) theory and
      the geometric characteristics of the targets in radar images are investigated.
      Currently, the signal detection algorithms based on the CS theory require knowing
      the prior knowledge of the sparsity of target signals. However, in practice, it
      is often impossible to know the sparsity in advance. To solve this problem, a
      novel sparsity adaptive matching pursuit (SAMP) detection algorithm is proposed.
      This algorithm executes the detection task by updating the support set and
      gradually increasing the sparsity to approximate the original signal. To verify
      the effectiveness of the proposed algorithm, the data collected in 2010 at
      Pingtan, which located on the coast of the East China Sea, were applied.
      Experiment results illustrate that the proposed method adaptively completes the
      detection task without knowing the signal sparsity, and the similar detection
      performance is close to the matching pursuit (MP) and orthogonal matching pursuit
      (OMP) detection algorithms.

PMID- 28505084
TI  - Food Sources of Energy and Nutrients in Infants, Toddlers, and Young Children
      from the Mexican National Health and Nutrition Survey 2012.
AB  - Food sources of nutrients in Mexican children are not well known. To fill the
      knowledge gap, dietary intake was assessed in 2057 children using a 24-hour
      dietary recall. All reported foods and beverages were assigned to one of 76 food
      groups. Percent contribution of each food group to nutrient intake was estimated
      for four age groups: 0-5.9, 6-11.9, 12-23.9, and 24-47.9 months. Breast milk,
      infant formula, and cow's milk were the top sources of energy and nutrients,
      especially in younger groups. Among infants aged 6-11.9 months, the top food
      sources of energy included soups and stews, cookies, fruit, tortillas, eggs and
      egg dishes, and traditional beverages. The same foods plus sweetened breads,
      dried beans, and sandwiches and tortas were consumed as the top sources of energy
      among toddlers and young children. Milk, soups, and stews were the top
      contributors for all nutrients and tortillas, eggs, and egg dishes were among the
      top contributors for iron and zinc. This study showed that low nutrient-dense
      cookies, sweetened breads, and traditional beverages were among the core foods
      consumed early in life in Mexico. This compromises the intake of more nutritious
      foods such as vegetables and fortified cereals and increases the risk of obesity.

PMID- 28505086
TI  - Raspberry-Like Bismuth Oxychloride on Mesoporous Siliceous Support for Sensitive
      Electrochemical Stripping Analysis of Cadmium.
AB  - BiOCl-SiO2 KIT-6 composite materials with raspberry-like structures are facilely
      prepared under hydrothermal conditions. The mesoporous siliceous support of SiO2
      KIT-6-incorporated BiOCl with enlarged yet refined surface morphology
      characterized by physiochemical methods exhibits an improved electrochemical
      performance. A sensitive electrochemical detection method of cadmium
      concentration using square wave anodic stripping voltammetry was developed based
      on BiOCl-SiO2 KIT-6 composite-modified glassy carbon electrodes, which displayed
      wide linear ranges of 0.5 to 10 MUg/L and 10 to 300 MUg/L and a detection limit
      of 65 ng/L. The sensitive, versatile and eco-friendly sensor was successfully
      applied for the determination of cadmium-spiked human blood samples.

PMID- 28505088
TI  - 1,4-Naphthoquinone Triggers Nematode Lethality by Inducing Oxidative Stress and
      Activating Insulin/IGF Signaling Pathway in Caenorhabditis elegans.
AB  - Plant-parasitic nematodes are destructive pathogens causing enormous economic
      losses worldwide. With the withdrawal of fumigants, organophosphates and
      carbamates, pathogenic nematode control is more difficult. Phytochemicals are the
      plant secondary metabolites and are friendly for men and the environment. For
      developing new nematocidal candidates, we screened 790 phytochemicals using the
      model organism Caenorhabditis elegans and found 10 active compounds, 3 of which
      were further evaluated for their inhibitory activities against egg hatching of C.
      elegans and J2 Meloidogyne incognita. Among them, 1,4-naphthoquinone (1,4-NQ) was
      the only compound that could kill more than 50% of targets at 50 MUg/mL,
      prompting us to investigate how 1,4-NQ triggers nematode lethality. In C.
      elegans, we observed that 1,4-NQ could influence reactive oxygen production,
      superoxide dismutase activity, and the heat-shock transcription factor (HSF)-1
      pathway, which indicated that 1,4-NQ stimulated significant oxidative stress.
      Furthermore, using quantitative RT-PCR and transgenetic nematodes, we revealed
      that 1,4-NQ lethality was related to the Insulin/IGF signaling (IIS) pathway, and
      the effect of 1,4-NQ on IIS pathway related genes indicated that 1,4-NQ could
      activate this pathway and suppress the expression of DAF-16 target genes. The
      triggering of oxidative stress and activation of the IIS pathway indicated that
      1,4-NQ operates through the generation of oxygen radicals, which can be lethal to
      C. elegans, thus making it an interesting lead compound for the development of
      future nematocides.

PMID- 28505089
TI  - Squeeze-Film Air Damping of a Five-Axis Electrostatic Bearing for Rotary
      Micromotors.
AB  - Air-film damping, which dominates over other losses, plays a significant role in
      the dynamic response of many micro-fabricated devices with a movable mass
      suspended by various bearing mechanisms. Modeling the damping characteristics
      accurately will be greatly helpful to the bearing design, control, and test in
      various micromotor devices. This paper presents the simulated and experimental
      squeeze-film air damping results of an electrostatic bearing for use in a rotary
      high-speed micromotor. It is shown that the boundary condition to solve the three
      dimensional Reynolds equation, which governs the squeeze-film damping in the air
      gap between the rotor and its surrounding stator sealed in a three-layer
      evacuated cavity, behaves with strong cross-axis coupling characteristics. To
      accurately characterize the damping effect, a set of multiphysics finite-element
      simulations are performed by computing both the rotor velocity and the
      distribution of the viscous damping force acting on the rotor. The damping
      characteristics varying with several key structure parameters are simulated and
      discussed to optimize the device structure for desirable rotor dynamics. An
      electrical measurement method is also proposed and applied to validate the
      numerical results of the damping coefficients experimentally. Given that the
      frequency response of the electric bearing is critically dependent on the damping
      coefficients at atmospheric pressure, a solution to the air-film damping
      measurement problem is presented by taking approximate curve fitting of multi
      axis experimental frequency responses. The measured squeeze-film damping
      coefficients for the five-axis electric bearing agrees well with the numerical
      solutions. This indicates that numerical multiphysics simulation is an effective
      method to accurately examine the air-film damping effect for complex device
      geometry and arbitrary boundary condition. The accurate damping coefficients
      obtained by FEM simulation will greatly simplify the design of the five-axis
      bearing control system and facilitate the initial suspension test of the rotor
      for various micromotor devices.

PMID- 28505087
TI  - The Effect of Diet on the Survival of Patients with Chronic Kidney Disease.
AB  - The prevalence of chronic kidney disease (CKD) is high and it is gradually
      increasing. Individuals with CKD should introduce appropriate measures to hamper
      the progression of kidney function deterioration as well as prevent the
      development or progression of CKD-related diseases. A kidney-friendly diet may
      help to protect kidneys from further damage. Patients with kidney damage should
      limit the intake of certain foods to reduce the accumulation of unexcreted
      metabolic products and also to protect against hypertension, proteinuria and
      other heart and bone health problems. Despite the fact that the influence of
      certain types of nutrients has been widely studied in relation to kidney function
      and overall health in CKD patients, there are few studies on the impact of a
      specific diet on their survival. Animal studies demonstrated prolonged survival
      of rats with CKD fed with protein-restricted diets. In humans, the results of
      studies are conflicting. Some of them indicate slowing down of the progression of
      kidney disease and reduction in proteinuria, but other underline significant
      worsening of patients' nutritional state, which can be dangerous. A recent
      systemic study revealed that a healthy diet comprising many fruits and
      vegetables, fish, legumes, whole grains, and fibers and also the cutting down on
      red meat, sodium, and refined sugar intake was associated with lower mortality in
      people with kidney disease. The aim of this paper is to review the results of
      studies concerning the impact of diet on the survival of CKD patients.

PMID- 28505090
TI  - Evaluation of Ochratoxin Recognition by Peptides Using Explicit Solvent Molecular
      Dynamics.
AB  - Biosensing platforms based on peptide recognition provide a cost-effective and
      stable alternative to antibody-based capture and discrimination of ochratoxin-A
      (OTA) vs. ochratoxin-B (OTB) in monitoring bioassays. Attempts to engineer
      peptides with improved recognition efficacy require thorough structural and
      thermodynamic characterization of the binding-competent conformations. Classical
      molecular dynamics (MD) approaches alone do not provide a thorough assessment of
      a peptide's recognition efficacy. In this study, in-solution binding properties
      of four different peptides, a hexamer (SNLHPK), an octamer (CSIVEDGK), NFO4
      (VYMNRKYYKCCK), and a 13-mer (GPAGIDGPAGIRC), which were previously generated for
      OTA-specific recognition, were evaluated using an advanced MD simulation approach
      involving accelerated configurational search and predictive modeling. Peptide
      configurations relevant to ochratoxin binding were initially generated using
      biased exchange metadynamics and the dynamic properties associated with the in
      solution peptide-ochratoxin binding were derived from Markov State Models. Among
      the various peptides, NFO4 shows superior in-solution OTA sensing and also shows
      superior selectivity for OTA vs. OTB due to the lower penalty associated with
      solvating its bound complex. Advanced MD approaches provide structural and
      energetic insights critical to the hapten-specific recognition to aid the
      engineering of peptides with better sensing efficacies.

PMID- 28505092
TI  - Molecular Characterization and Expression Profiling of Tomato GRF Transcription
      Factor Family Genes in Response to Abiotic Stresses and Phytohormones.
AB  - Growth regulating factors (GRFs) are plant-specific transcription factors that
      are involved in diverse biological and physiological processes, such as growth,
      development and stress and hormone responses. However, the roles of GRFs in
      vegetative and reproductive growth, development and stress responses in tomato
      (Solanum lycopersicum) have not been extensively explored. In this study, we
      characterized the 13 SlGRF genes. In silico analysis of protein motif
      organization, intron-exon distribution, and phylogenetic classification confirmed
      the presence of GRF proteins in tomato. The tissue-specific expression analysis
      revealed that most of the SlGRF genes were preferentially expressed in young and
      growing tissues such as flower buds and meristems, suggesting that SlGRFs are
      important during growth and development of these tissues. Some of the SlGRF genes
      were preferentially expressed in fruits at distinct developmental stages
      suggesting their involvement in fruit development and the ripening process. The
      strong and differential expression of different SlGRFs under NaCl, drought, heat,
      cold, abscisic acid (ABA), and jasmonic acid (JA) treatment, predict possible
      functions for these genes in stress responses in addition to their growth
      regulatory functions. Further, differential expression of SlGRF genes upon
      gibberellic acid (GA3) treatment indicates their probable function in flower
      development and stress responses through a gibberellic acid (GA)-mediated
      pathway. The results of this study provide a basis for further functional
      analysis and characterization of this important gene family in tomato.

PMID- 28505095
TI  - Behavioural Profiles of Brown and Sloth Bears in Captivity.
AB  - Three brown bear (Ursusarctosarctos) individuals and two sloth bear
      (Melursusursinusinornatus) individuals were observed in captivity to produce
      behavioural profiles for each individual. Data collected through behavioural
      observations were used to produce activity budgets, and to identify space usage
      and certain aspects of social behavior. Behaviour monitoring allowed the
      researchers to evaluate the welfare of the animals by identifying the occurrence
      of stereotypic behaviours, which are sometimes associated with stress.
      Behavioural profiles were created using data obtained through behavioural
      observations (coding) and keeper questionnaires (rating). The behavioural
      observations indicated a number of stereotypic behaviours in sloth bears but not
      in brown bears. The uniformity of zone usage was calculated to investigate if the
      enclosure size and features were adequate for use, and a social aspect of
      otherwise solitary animals was also identified. The behavioural profiles
      generated through coding and rating were compared to determine the reliability
      between these two methods in Ursids. Profiles were not compared between
      individuals since this study is not a comparison between different personality
      types but rather an effort (one of the few ones existing in literature) to select
      a valid and reproducible methodology capable of assessing personality in bears.

PMID- 28505094
TI  - Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides
      var. fagaroides.
AB  - Giardiasis, a diarrheal disease, is highly prevalent in developing countries.
      Several drugs are available for the treatment of this parasitosis; unfortunately,
      all of them have variable efficacies and adverse effects. Bursera fagaroides has
      been known for its anti-inflammatory and antidiarrheal properties in Mexican
      traditional medicine. We investigated the in vitro anti-giardial activities of
      four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides,
      namely, 5'-desmethoxy-beta-peltatin-A-methylether (5-DES), acetylpodophyllotoxin
      (APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the
      Giardia adhesion and electron microscopy images revealed morphological
      alterations in the caudal region, ventral disk, membrane, and flagella, to
      different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the
      Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated
      that APOD displayed direct antigiardial killing activity and low toxicity on Caco
      2 cells. This finding makes it an attractive potential starting point for new
      antigiardial drugs.

PMID- 28505091
TI  - The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis.
AB  - Eukaryotic cells have to cope with the constant generation of reactive oxygen
      species (ROS). Although the excessive production of ROS might be deleterious for
      cell biology, there is a plethora of evidence showing that moderate levels of ROS
      are important for the control of cell signaling and gene expression. The family
      of the nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases or
      Nox) has evolved to produce ROS in response to different signals; therefore, they
      fulfil a central role in the control of redox signaling. The role of NADPH
      oxidases in vascular physiology has been a field of intense study over the last
      two decades. In this review we will briefly analyze how ROS can regulate
      signaling and gene expression. We will address the implication of NADPH oxidases
      and redox signaling in angiogenesis, and finally, the therapeutic possibilities
      derived from this knowledge will be discussed.

PMID- 28505093
TI  - The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function.
AB  - A neuron is unique in its ability to dynamically modify its transcriptional
      output in response to synaptic activity while maintaining a core gene expression
      program that preserves cellular identity throughout a lifetime that is longer
      than almost every other cell type in the body. A contributing factor to the
      immense adaptability of a neuron is its unique epigenetic landscape that elicits
      locus-specific alterations in chromatin architecture, which in turn influences
      gene expression. One such epigenetic modification that is sensitive to changes in
      synaptic activity, as well as essential for maintaining cellular identity, is DNA
      methylation. The focus of this article is on the importance of DNA methylation in
      neuronal function, summarizing recent studies on critical players in the
      establishment of (the "writing"), the modification or erasure of (the "editing"),
      and the mediation of (the "reading") DNA methylation in neurodevelopment and
      neuroplasticity. One "reader" of DNA methylation in particular, methyl-CpG
      binding protein 2 (MeCP2), is highlighted, given its undisputed importance in
      neuronal function.

PMID- 28505097
TI  - Nonlinear Parameter Identification of a Resonant Electrostatic MEMS Actuator.
AB  - We experimentally investigate the primary superharmonic of order two and
      subharmonic of order one-half resonances of an electrostatic MEMS actuator under
      direct excitation. We identify the parameters of a one degree of freedom (1-DOF)
      generalized Duffing oscillator model representing it. The experiments were
      conducted in soft vacuum to reduce squeeze-film damping, and the actuator
      response was measured optically using a laser vibrometer. The predictions of the
      identified model were found to be in close agreement with the experimental
      results. We also identified the noise spectral density of process (actuation
      voltage) and measurement noise.

PMID- 28505096
TI  - Attenuation of Drought Stress in Brassica Seedlings with Exogenous Application of
      Ca2+ and H2O2.
AB  - Drought is one of the most common abiotic stresses, affecting the growth and
      productivity of crop plants globally, particularly in arid and semi-arid regions.
      Different strategies are used to mitigate the impact of drought among crop
      plants. Exogenous application of different substances are known to decrease the
      effects of various abiotic stresses, including drought stress. The aim of this
      study was to evaluate the effect of Ca2+ and H2O2 in developing drought stress
      tolerance in Brassica napus "Bulbul-98" seedlings. Brassica napus "Bulbul-98"
      seedlings were exposed to 5, 10 and 15 mM Ca2+ and 2, 5 and 10 MUM H2O2
      concentrations twice at an interval of two days for up to 20 days after
      germination. Drought stress decreased relative water content (RWC), chlorophyll
      content and increased proline, H2O2, soluble protein and electrolyte leakage in
      Brassica seedlings. Exogenous Ca2+ (5, 10,15 mM) and H2O2 (2, 5, 10 MUM)
      supplementations, during drought stress induction, showed a significant increase
      in RWC by 5.4%, 18.06%, 26.2% and 6.87%, 13.9%, 18.3% respectively. Similarly,
      with the exogenous application of Ca2+ (5, 10, 15 mM) and H2O2 (2, 5, 10 MUM),
      chlorophyll content was increased by 15.03%, 22.2%, and 28.4%, and 9.6%, 23.3%,
      and 27.5% respectively. It was confirmed that the seedlings under drought stress
      that were supplemented with Ca2+ and H2O2 recovered from water content reduction
      and chlorosis, and were able to grow normally.

PMID- 28505098
TI  - Alcohols as Substrates and Solvents for the Construction of 3-Alkoxylated-2
      Oxindoles by Direct Alkoxylation of 3-Halooxindoles.
AB  - Described herein is an environmentally benign method for the synthesis of
      multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3
      halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole
      scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil
      bath at 35  degrees C for 24 h. A particularly valuable feature of this method
      was the development of environment-friendly chemistry using alcohols 2 as both
      the substrates and solvents in the presence of a catalytic amount of base.

PMID- 28505099
TI  - Mutational and Kinetic Analysis of Lesion Recognition by Escherichia coli
      Endonuclease VIII.
AB  - Escherichia coli endonuclease VIII (Endo VIII) is a DNA glycosylase with
      substrate specificity for a wide range of oxidatively damaged pyrimidine bases.
      Endo VIII catalyzes hydrolysis of the N-glycosidic bond and beta, delta
      elimination of 3'- and 5'-phosphate groups of an apurinic/apyrimidinic site.
      Single mutants of Endo VIII L70S, L70W, Y71W, F121W, F230W, and P253W were
      analyzed here with the aim to elucidate the kinetic mechanism of protein
      conformational adjustment during damaged-nucleotide recognition and catalytic
      complex formation. F121W substitution leads to a slight reduction of DNA binding
      and catalytic activity. F230W substitution slows the rate of the delta
      elimination reaction indicating that interaction of Phe230 with a 5'-phosphate
      group proceeds in the latest catalytic step. P253W Endo VIII has the same
      activity as the wild type (WT) enzyme. Y71W substitution slightly reduces the
      catalytic activity due to the effect on the later steps of catalytic-complex
      formation. Both L70S and L70W substitutions significantly decrease the catalytic
      activity, indicating that Leu70 plays an important role in the course of enzyme
      DNA catalytic complex formation. Our data suggest that Leu70 forms contacts with
      DNA earlier than Tyr71 does. Therefore, most likely, Leu70 plays the role of a
      DNA lesion "sensor", which is used by Endo VIII for recognition of a DNA damage
      site.

PMID- 28505100
TI  - Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming:
      State-of-the-Art and Challenges Ahead.
AB  - Animal-derived antivenoms constitute the mainstay in the therapy of snakebite
      envenoming. The efficacy of antivenoms to neutralize toxicity of medically
      relevant snake venoms has to be demonstrated through meticulous preclinical
      testing before their introduction into the clinical setting. The gold standard in
      the preclinical assessment and quality control of antivenoms is the
      neutralization of venom-induced lethality. In addition, depending on the
      pathophysiological profile of snake venoms, the neutralization of other toxic
      activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming,
      dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need
      to develop laboratory assays to evaluate neutralization of other relevant venom
      activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in
      Toxinology is of utmost importance, and some advances have been performed in
      their implementation. A significant leap forward in the study of the
      immunological reactivity of antivenoms against venoms has been the development of
      "antivenomics", which brings the analytical power of mass spectrometry to the
      evaluation of antivenoms. International partnerships are required to assess the
      preclinical efficacy of antivenoms against snake venoms in different regions of
      the world in order to have a detailed knowledge on the neutralizing profile of
      these immunotherapeutics.

PMID- 28505103
TI  - Neuronal Migration and AUTS2 Syndrome.
AB  - Neuronal migration is one of the pivotal steps to form a functional brain, and
      disorganization of this process is believed to underlie the pathology of
      psychiatric disorders including schizophrenia, autism spectrum disorders (ASD)
      and epilepsy. However, it is not clear how abnormal neuronal migration causes
      mental dysfunction. Recently, a key gene for various psychiatric diseases, the
      Autism susceptibility candidate 2 (AUTS2), has been shown to regulate neuronal
      migration, which gives new insight into understanding this question.
      Interestingly, the AUTS2 protein has dual functions: Cytoplasmic AUTS2 regulates
      actin cytoskeleton to control neuronal migration and neurite extension, while
      nuclear AUTS2 controls transcription of various genes as a component of the
      polycomb complex 1 (PRC1). In this review, we discuss AUTS2 from the viewpoint of
      human genetics, molecular function, brain development, and behavior in animal
      models, focusing on its role in neuronal migration.

PMID- 28505101
TI  - Dairy Propionibacteria: Versatile Probiotics.
AB  - Dairy propionibacteria are used as cheese ripening starters, as biopreservative
      and as beneficial additives, in the food industry. The main species,
      Propionibacterium freudenreichii, is known as GRAS (Generally Recognized As Safe,
      USA, FDA). In addition to another dairy species, Propionibacterium
      acidipropionici, they are included in QPS (Qualified Presumption of Safety) list.
      Additional to their well-known technological application, dairy propionibacteria
      increasingly attract attention for their promising probiotic properties. The
      purpose of this review is to summarize the probiotic characteristics of dairy
      propionibacteria reported by the updated literature. Indeed, they meet the
      selection criteria for probiotic bacteria, such as the ability to endure
      digestive stressing conditions and to adhere to intestinal epithelial cells. This
      is a prerequisite to bacterial persistence within the gut. The reported
      beneficial effects are ranked according to property's type: microbiota
      modulation, immunomodulation, and cancer modulation. The proposed molecular
      mechanisms are discussed. Dairy propionibacteria are described as producers of
      nutraceuticals and beneficial metabolites that are responsible for their
      versatile probiotic attributes include short chain fatty acids (SCFAs),
      conjugated fatty acids, surface proteins, and 1,4-dihydroxy-2-naphtoic acid
      (DHNA). These metabolites possess beneficial properties and their production
      depends on the strain and on the growth medium. The choice of the fermented food
      matrix may thus determine the probiotic properties of the ingested product. This
      review approaches dairy propionibacteria, with an interest in both technological
      abilities and probiotic attributes.

PMID- 28505102
TI  - Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and
      Possible Mechanisms.
AB  - Osteoporosis is an age-related chronic disease characterized by a loss of bone
      mass and quality, and is associated with an increased risk of fragility
      fractures. Postmenopausal women are at the greatest risk of developing
      osteoporosis due to the cessation in ovarian hormone production, which causes
      accelerated bone loss. As the demographic shifts to a more aged population, a
      growing number of postmenopausal women will be afflicted with osteoporosis.
      Certain lifestyle factors, including nutrition and exercise, are known to reduce
      the risk of developing osteoporosis and therefore play an important role in bone
      health. In terms of nutrition, accumulating evidence suggests that dried plum
      (Prunus domestica L.) is potentially an efficacious intervention for preventing
      and reversing bone mass and structural loss in an ovariectomized rat model of
      osteoporosis, as well as in osteopenic postmenopausal women. Here, we provide
      evidence supporting the efficacy of dried plum in preventing and reversing bone
      loss associated with ovarian hormone deficiency in rodent models and in humans.
      We end with the results of a recent follow-up study demonstrating that
      postmenopausal women who previously consumed 100 g dried plum per day during our
      one-year clinical trial conducted five years earlier retained bone mineral
      density to a greater extent than those receiving a comparative control.
      Additionally, we highlight the possible mechanisms of action by which bioactive
      compounds in dried plum exert bone-protective effects. Overall, the findings of
      our studies and others strongly suggest that dried plum in its whole form is a
      promising and efficacious functional food therapy for preventing bone loss in
      postmenopausal women, with the potential for long-lasting bone-protective
      effects.

PMID- 28505104
TI  - Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening
      Marker by Liquid Chromatography Tandem-mass Spectrometry.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into
      systemic inflammation and joint deformity. RA diagnosis is a complicated
      procedure, and early diagnostic methods are insufficient. Therefore, in this
      study, we attempted to identify new markers to improve the accuracy of RA
      prescreening. e identified differentially expressed proteins (DEPs) by using
      liquid chromatography tandem-mass spectrometry in health-prescreening sera with
      high rheumatoid factor (RF) values, and compared the findings with those from
      sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated,
      and 57 were downregulated in high-RF sera. Pathway analysis revealed that these
      DEPs were related to immune responses. Additionally, four DEPs were statistically
      analyzed by proteomic analysis; of these, SAA4 was significantly validated in
      individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly
      upregulated in RA patients (n = 40, 66.43 +/- 12.97 ng/mL) compared with normal
      controls (n = 40, 4.79 +/- 0.95 ng/mL) and had a higher area under the curve than
      C-reactive protein. Thus, we identified SAA4 as a protein that was positively
      correlated with RF and RA. SAA4 may represent a novel prescreening marker for the
      diagnosis of RA.

PMID- 28505106
TI  - Human Chorionic Gonadotropin: The Pregnancy Hormone and More.
AB  - To thoroughly review the uses of human chorionic gonadotropin (hCG) related to
      the process of reproduction and also assess new, non-traditional theories. Review
      of the international literature and research studies. hCG and its receptor,
      LH/CGR, are expressed in numerous sites of the reproductive tract, both in
      gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization,
      implantation and early embryo development. Moreover, hCG seems to have a
      potential role as an anti-rejection agent in solid organ transplantation. Future
      research needs to focus extensively on the functions of hCG and its receptor
      LH/CGR, in an effort to reveal known, as well as unknown clinical potentials.

PMID- 28505105
TI  - New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in
      Alzheimer's Disease.
AB  - The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates
      important processes in cells, such as the cell cycle, by targeting a set of
      substrates for degradation. In the last decade, APC/C has been related to several
      major functions in the nervous system, including axon guidance, synaptic
      plasticity, neurogenesis, and neuronal survival. Interestingly, some of the
      identified APC/C substrates have been related to neurodegenerative diseases.
      There is an accumulation of some degradation targets of APC/C in Alzheimer's
      disease (AD) brains, which suggests a dysregulation of the protein complex in the
      disorder. Moreover, recently evidence has been provided for an inactivation of
      APC/C in AD. It has been shown that oligomers of the AD-related peptide, Abeta,
      induce degradation of the APC/C activator subunit cdh1, in vitro in neurons in
      culture and in vivo in the mouse hippocampus. Furthermore, in the AD mouse model
      APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when
      compared to age-matched wildtype mice. In this review, we provide a complete list
      of APC/C substrates that are involved in the nervous system and we discuss their
      functions. We also summarize recent studies that show neurobiological effects in
      cdh1 knockout mouse models. Finally, we discuss the role of APC/C in the
      pathophysiology of AD.

PMID- 28505107
TI  - Raman Spectroscopy of Head and Neck Cancer: Separation of Malignant and Healthy
      Tissue Using Signatures Outside the "Fingerprint" Region.
AB  - The ability to rapidly and accurately discriminate between healthy and malignant
      tissue offers surgeons a tool for in vivo analysis that would potentially reduce
      operating time, facilitate quicker recovery, and improve patient outcomes. To
      this end, we investigate discrimination between diseased tissue and adjacent
      healthy controls from patients with head and neck cancer using near-infrared
      Raman spectroscopy. Our results indicate previously unreported peaks in the Raman
      spectra that lie outside the conventional "fingerprint" region (400 cm-1-1800 cm 
      1) played an important role in our analysis and in discriminating between the
      tissue classes. Preliminary multivariate statistical analyses of the Raman
      spectra indicate that discrimination between diseased and healthy tissue is
      possible based on these peaks.

PMID- 28505108
TI  - Measurement of Vibrations in Two Tower-Typed Assistant Personal Robot
      Implementations with and without a Passive Suspension System.
AB  - This paper presents the vibration pattern measurement of two tower-typed
      holonomic mobile robot prototypes: one based on a rigid mechanical structure, and
      the other including a passive suspension system. Specific to the tower-typed
      mobile robots is that the vibrations that originate in the lower part of the
      structure are transmitted and amplified to the higher areas of the tower, causing
      an unpleasant visual effect and mechanical stress. This paper assesses the use of
      a suspension system aimed at minimizing the generation and propagation of
      vibrations in the upper part of the tower-typed holonomic robots. The two robots
      analyzed were equipped with onboard accelerometers to register the acceleration
      over the X, Y, and Z axes in different locations and at different velocities. In
      all the experiments, the amplitude of the vibrations showed a typical Gaussian
      pattern which has been modeled with the value of the standard deviation. The
      results have shown that the measured vibrations in the head of the mobile robots,
      including a passive suspension system, were reduced by a factor of 16.

PMID- 28505109
TI  - The Vip3Ag4 Insecticidal Protoxin from Bacillus thuringiensis Adopts A Tetrameric
      Configuration That Is Maintained on Proteolysis.
AB  - The Vip3 proteins produced during vegetative growth by strains of the bacterium
      Bacillus thuringiensis show insecticidal activity against lepidopteran insects
      with a mechanism of action that may involve pore formation and apoptosis. These
      proteins are promising supplements to our arsenal of insecticidal proteins, but
      the molecular details of their activity are not understood. As a first step in
      the structural characterisation of these proteins, we have analysed their
      secondary structure and resolved the surface topology of a tetrameric complex of
      the Vip3Ag4 protein by transmission electron microscopy. Sites sensitive to
      proteolysis by trypsin are identified and the trypsin-cleaved protein appears to
      retain a similar structure as an octomeric complex comprising four copies each of
      the ~65 kDa and ~21 kDa products of proteolysis. This processed form of the toxin
      may represent the active toxin. The quality and monodispersity of the protein
      produced in this study make Vip3Ag4 a candidate for more detailed structural
      analysis using cryo-electron microscopy.

PMID- 28505111
TI  - Effects of Mead Wort Heat Treatment on the Mead Fermentation Process and
      Antioxidant Activity.
AB  - The effects of mead wort heat treatment on the mead fermentation process and
      antioxidant activity were tested. The experiment was conducted with the use of
      two different honeys (multiflorous and honeydew) collected from the Lower Silesia
      region (Poland). Heat treatment was performed with the use of a traditional
      technique (gently boiling), the more commonly used pasteurization, and without
      heat treatment (control). During the experiment fermentation dynamics were
      monitored using high performance liquid chromatography with refractive index
      detection (HPLC-RID). Total antioxidant capacity (TAC) and total phenolic content
      (TPC) were estimated for worts and meads using UV/Vis spectrophotometric
      analysis. The formation of 5-hydroxymethylfurfural (HMF) was monitored by HPLC
      analyses. Heat treatment had a great impact on the final antioxidant capacity of
      meads.

PMID- 28505110
TI  - Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate
      High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux.
AB  - Epidemiological and experimental studies reveal that Western dietary patterns
      contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary
      polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression
      of kidney injury. This study aimed to investigate the renal protective effects of
      GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly
      divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three
      diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group
      exhibited renal injuries by increased serum cystatin C levels and urinary N
      acetyl-beta-d-glucosaminidase activity, which can be ameliorated by GTPs.
      Meanwhile, autophagy impairment as denoted by autophagy-lysosome related
      proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1,
      was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities
      and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux
      suppression was detected in palmitic acid (PA)-treated human proximal tubular
      epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate
      (EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated
      protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells.
      These findings revealed that GTPs mimic the effects of DR to induce autophagy and
      exert a renal protective effect by alleviating HFD-induced autophagy suppression.

PMID- 28505112
TI  - Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand
      Bound Copper(I).
AB  - The CuAAC 'click' reaction was used to couple alkyne-functionalized lanthanide
      DOTA complexes to a range of fluorescent antennae. Screening of the antenna
      components was aided by comparison of the luminescent output of the resultant
      sensors using data normalized to account for reaction conversion as assessed by
      IR. A maximum 82-fold enhanced signal:background luminescence output was achieved
      using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is
      specific to the presence of copper(I). This optimized complex provides a new lead
      design for lanthanide-DOTA complexes which can act as irreversible 'turn-on'
      catalytic sensors for the detection of ligand-bound copper(I).

PMID- 28505113
TI  - Evaluation of Efficient and Practical Methods for the Preparation of
      Functionalized Aliphatic Trifluoromethyl Ethers.
AB  - The "chlorination/fluorination" technique for aliphatic trifluoromethyl ether
      synthesis was investigated and a range of products with various functional groups
      was prepared. The results were compared with oxidative desulfurization
      fluorination of xanthates with the same structure.

PMID- 28505115
TI  - Photosensor-Based Latency Measurement System for Head-Mounted Displays.
AB  - In this paper, a photosensor-based latency measurement system for head-mounted
      displays (HMDs) is proposed. The motion-to-photon latency is the greatest reason
      for motion sickness and dizziness felt by users when wearing an HMD system.
      Therefore, a measurement system is required to accurately measure and analyze the
      latency to reduce these problems. The existing measurement system does not
      consider the actual physical movement in humans, and its accuracy is also very
      low. However, the proposed system considers the physical head movement and is
      highly accurate. Specifically, it consists of a head position model-based rotary
      platform, pixel luminance change detector, and signal analysis and calculation
      modules. Using these modules, the proposed system can exactly measure the
      latency, which is the time difference between the physical movement for a user
      and the luminance change of an output image. In the experiment using a commercial
      HMD, the latency was measured to be up to 47.05 ms. In addition, the measured
      latency increased up to 381.17 ms when increasing the rendering workload in the
      HMD.

PMID- 28505114
TI  - Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient
      Min Mice.
AB  - Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional
      target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and
      is suggested to enhance cancer progression. In this study, the effect of
      deficiency of OPN on intestinal tumor development in Apc-deficient Min mice was
      investigated. At 16 weeks of age, the number of small intestinal polyps in
      Min/OPN(+/-) and Min/OPN(-/-) mice was lower than that of Min/OPN(+/+) mice.
      Colorectal tumor incidences and multiplicities in Min/OPN(+/-) and Min/OPN(-/-)
      mice were significantly lower than those in Min/OPN(+/+) mice, being 48% and 0.6
      +/- 0.8, 50% and 0.8 +/- 0.9 vs. 80% and 1.6 +/- 1.7, respectively. OPN
      expression in colorectal tumors was strongly upregulated in Min/OPN(+/+) compared
      to adjacent non-tumor parts, but was decreased in Min/OPN(+/-) and not detected
      in Min/OPN(-/-). Targets of OPN, matrix metalloproteinases (MMPs)-3, -9, and -13
      were lowered by OPN deficiency. Macrophage marker F4/80 in colorectal tumors was
      also lowered by OPN deficiency. MMP-9 expression was observed in tumor cells and
      tumor-infiltrating neutrophils. These results indicate that induction of OPN by
      aberrant Wnt signaling could enhance colorectal tumor development in part by
      upregulation of MMP-3, -9, and -13 and infiltration of macrophage and
      neutrophils. Suppression of OPN expression could contribute to tumor prevention,
      but complete deficiency of OPN may cause some adverse effects.

PMID- 28505116
TI  - Surface Modification and Damage of MeV-Energy Heavy Ion Irradiation on Gold
      Nanowires.
AB  - Gold nanowires with diameters ranging from 20 to 90 nm were fabricated by the
      electrochemical deposition technique in etched ion track polycarbonate templates
      and were then irradiated by Xe and Kr ions with the energy in MeV range. The
      surface modification of nanowires was studied by scanning electron microscopy
      (SEM) and transmission electron microscopy (TEM) characterizations. Different
      craters with and without protrusion on the gold nanowires were analyzed, and the
      two corresponding formation mechanisms, i.e., plastic flow and micro-explosion,
      were investigated. In addition, the sputtered gold nanoparticles caused by ion
      irradiation were studied and it was confirmed that the surface damage produced in
      gold nanowires was increased as the diameter of the nanowires decreased. It was
      also found that heavy ion irradiation can also create stacking fault tetrahedrons
      (SFTs) in gold nanowires and three different SFTs were confirmed in irradiated
      nanowires. A statistical analysis of the size distribution of SFTs in gold
      nanowires proved that the average size distribution of SFT was positively related
      to the nuclear stopping power of incident ions, i.e., the higher nuclear stopping
      power of incident ions could generate SFT with a larger average size in gold
      nanowires.

PMID- 28505118
TI  - Communicatively Constructing the Bright and Dark Sides of Hope: Family
      Caregivers' Experiences during End of Life Cancer Care.
AB  - (1) Background: The communication of hope is complicated, particularly for family
      caregivers in the context of cancer who struggle to maintain hope for themselves
      and their loved ones in the face of terminality. In order to understand these
      complexities, the current study examines the bright and dark sides of how hope is
      communicated across the cancer journey from the vantage point of bereaved family
      caregivers; (2) Methods: We analyzed interviews with bereaved family caregivers
      using qualitative thematic and case oriented strategies to identify patterns in
      the positive and negative lived experiences when communicating about hope at the
      end of life; (3) Results: Two overarching patterns of hope emerged. Those who
      experienced hope as particularized (focused on cure) cited communication about
      false hope, performing (faking it), and avoidance. Those who transitioned from
      particularized to generalized hope (hope for a good death) reported acceptance,
      the communication of hope as social support, prioritizing family, and balancing
      hope and honesty; (4) Conclusion: Family caregivers face myriad complexities in
      managing the bright and dark sides of hope. Interventions should encourage
      concurrent oncological and palliative care, increased perspective-taking among
      family members, and encourage the transition from particularized to generalized
      hope.

PMID- 28505119
TI  - Laxative Effects of Dietary Supplementation with Sujiaonori Algal Biomaterial in
      Japanese Adult Women with Functional Constipation: A Case Study.
AB  - Constipation is a gastrointestinal motility disorder that represents a major
      health problem in Japan. Approximately 26% of young Japanese adult women are
      reported to have this complaint. We report on the health effects of daily intake
      of Sujiaonori algal biomaterial (SBM) on constipation on 12 Japanese adult women.
      Data are from a four-week dietary intervention study on the health effects of
      daily Sujiaonori supplementation on cardiovascular, skin, and gastrointestinal
      health in which 32 adult Japanese volunteers (age range: 20-54 years)
      participated. They underwent clinical and laboratory investigations, and
      completed two study questionnaires (the brief diet history questionnaire (BDHQ)
      and the current health questionnaire) before and after dietary intervention. Of
      the 12 women volunteers with functional constipation, there were six SBM
      supplemented subjects who received 3 g of Sujiaonori powder twice daily during
      meal, whereas the six others (controls) were from the group of those who took 3 g
      of a power made of 70% corn starch and 30% Japanese spinach mixture. The analysis
      of data on daily nutrient intake showed no significant dietary changes for
      nutrients (minerals, proteins, fiber, fat) and calorie intake (except alcohol
      intake that was reduced) in both groups. In SBM group, a significant reduction of
      the proportion of women with constipation was observed (p < 0.001), whereas no
      significant change was noted within the control group (p > 0.05). When both
      groups were compared, SBM was more effective than the control product; 66.7%
      (4/6) of SBM-supplemented women had their constipation relieved, whereas only one
      control (16.7%) controls benefited from dietary intervention (p < 0.001). In
      addition, no adverse effect was reported in the SBM group, whereas two controls
      reported nausea at post-survey. These results suggest that Sujiaonori contains
      compounds that can improve gastrointestinal function and relieve constipation.

PMID- 28505117
TI  - HIV-Enhancing and HIV-Inhibiting Properties of Cationic Peptides and Proteins.
AB  - Cationic antimicrobial peptides and proteins have historically been ascribed
      roles in innate immunity that infer killing of microbial and viral pathogens and
      protection of the host. In the context of sexually transmitted HIV-1, we take an
      unconventional approach that questions this paradigm. It is becoming increasingly
      apparent that many of the cationic polypeptides present in the human genital or
      anorectal mucosa, or human semen, are capable of enhancing HIV-1 infection, often
      in addition to other reported roles as viral inhibitors. We explore how the in
      vivo environment may select for or against the HIV-enhancing aspects of these
      cationic polypeptides by focusing on biological relevance. We stress that the
      distinction between enhancing and inhibiting HIV-1 infection is not mutually
      exclusive to specific classes of cationic polypeptides. Understanding how virally
      enhancing peptides and proteins act to promote sexual transmission of HIV-1 would
      be important for the design of topical microbicides, mucosal vaccines, and other
      preventative measures.

PMID- 28505120
TI  - In Situ Raman Analysis of CO2-Assisted Drying of Fruit-Slices.
AB  - This work explores the feasibility of applying in situ Raman spectroscopy for the
      online monitoring of the supercritical carbon dioxide (SC-CO2) drying of fruits.
      Specifically, we investigate two types of fruits: mango and persimmon. The drying
      experiments were carried out inside an optical accessible vessel at 10 MPa and
      313 K. The Raman spectra reveal: (i) the reduction of the water from the fruit
      slice and (ii) the change of the fruit matrix structure during the drying
      process. Two different Raman excitation wavelengths were compared: 532 nm and 785
      nm. With respect to the quality of the obtained spectra, the 532 nm excitation
      wavelength was superior due to a higher signal-to-noise ratio and due to a
      resonant excitation scheme of the carotenoid molecules. It was found that the
      absorption of CO2 into the fruit matrix enhances the extraction of water, which
      was expressed by the obtained drying kinetic curve.

PMID- 28505122
TI  - Dynamic and Steady Characteristics of Polymer-Ceramic Pressure-Sensitive Paint
      with Variation in Layer Thickness.
AB  - Polymer-ceramic pressure-sensitive paint (PC-PSP) has been investigated as a
      surface-pressure sensor for unsteady aerodynamics and short duration
      measurements. This PSP provides a fast response to a change in pressures with a
      spray-coating ability. Because it is sprayed onto an aerodynamic surface, the
      thickness of PC-PSP may play an important role in determining the performance of
      this sensor. The thickness of other fast PSPs, such as anodized aluminum pressure
      sensitive paint, is a major factor in determining its performance. We vary the
      thickness of PC-PSP from 10 to 240 MUm in order to study its effects on PSP
      measurement characteristics including time response, signal level, pressure
      sensitivity, and temperature dependency. It is found that the thickness does
      affect these characteristics. However, a thickness over 80 MUm provides uniform
      performance in these characteristics.

PMID- 28505121
TI  - Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic
      Rats by Kaempferol.
AB  - There is growing evidence that chronic hyperglycemia leads to the formation of
      advanced glycation end products (AGEs) which exerts its effect via interaction
      with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation
      results in oxidative stress and inflammation. It is well known that this
      mechanism is involved in the pathogenesis of cardiovascular disease in diabetes.
      Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic,
      and anti-inflammatory activities. However, little is known about the effect of
      kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats.
      Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg;
      i.p.), and rats with glucose level >250 mg/dL were considered as diabetic.
      Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg;
      i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by
      one-stage ligation of the left anterior descending coronary artery for 45 min
      followed by reperfusion for 60 min. After completion of surgery, rats were
      sacrificed and the heart tissue was processed for biochemical, morphological, and
      molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia,
      maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized
      oxidative stress, and preserved morphological alterations. In addition, there was
      decreased level of inflammatory markers (tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), and NF-kappaB), inhibition of active c-Jun N-terminal
      kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated
      kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated
      apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase
      3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive
      cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion,
      kaempferol attenuated myocardial ischemia-reperfusion injury in diabetic rats by
      reducing AGE-RAGE/ mitogen activated protein kinase (MAPK) induced oxidative
      stress and inflammation.

PMID- 28505123
TI  - Perceived Health Benefits and Willingness to Pay for Parks by Park Users:
      Quantitative and Qualitative Research.
AB  - Whilst a growing body of evidence demonstrates people derive a range of health
      and wellbeing benefits from visiting parks, only a limited number of attempts
      have been made to provide a complementary economic assessment of parks. The aim
      of this exploratory study was to directly estimate the perceived health and
      wellbeing benefits attained from parks and the economic value assigned to parks
      by park users in Victoria, Australia. The research employed a mixed methods
      approach (survey and interviews) to collect primary data from a selection of 140
      park users: 100 from two metropolitan parks in Melbourne and 40 from a park on
      the urban fringe of Melbourne, Victoria. Our findings suggest that park users
      derive a range of perceived physical, mental/spiritual, and social health
      benefits, but park use was predominantly associated with physical health
      benefits. Overall, our exploratory study findings suggest that park users are
      willing to pay for parks, as they highly value them as places for exercising,
      socialising, and relaxing. Importantly, most people would miss parks if they did
      not exist. The findings aim to provide park managers, public health advocates,
      and urban policy makers with evidence about the perceived health and wellbeing
      benefits of park usage and the economic value park visitors place on parks.

PMID- 28505124
TI  - Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates
      Produced in Different Bioreactors.
AB  - Heparin and heparan sulfate are structurally-related carbohydrates with
      therapeutic applications in anticoagulation, drug delivery, and regenerative
      medicine. This study explored the effect of different bioreactor conditions on
      the production of heparin/heparan sulfate chains via the recombinant expression
      of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred
      tank reactors promoted the production of serglycin decorated with heparin/heparan
      sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in
      the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate
      chains. The serglycin produced in tissue culture flasks was effective in binding
      and signaling fibroblast growth factor 2, indicating the utility of this molecule
      in drug delivery and regenerative medicine applications in addition to its well
      known anticoagulant activity.

PMID- 28505125
TI  - Isolaurenidificin and Bromlaurenidificin, Two New C15-Acetogenins from the Red
      Alga Laurencia obtusa.
AB  - Chromatographic fractionation of the CH2Cl2/MeOH extract of the Red Sea red alga
      Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C15-acetogenins,
      namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures
      were elucidated based on extensive analyses of their spectral data. Compounds 1
      and 2 showed no toxicity (LC50 > 12 mM) using Artemia salina as test organism.
      Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and
      PC-3 cells, however, they exhibited a relatively potent cytotoxic activity
      against peripheral blood neutrophils. This can be attributed partly to induction
      of apoptosis.

PMID- 28505126
TI  - Unprocessed Meat Consumption and Incident Cardiovascular Diseases in Korean
      Adults: The Korean Genome and Epidemiology Study (KoGES).
AB  - Meat consumption has been shown to be associated with cardiovascular disease
      (CVD) risk in Western societies; however, epidemiological data are limited on the
      Korean population. Therefore, we examined the associations between unprocessed
      meat consumption and CVD incidence in Korea. Data were derived from the Ansung
      Ansan cohort (2001-2012), including 9370 adults (40-69 years) without CVD or
      cancer at baseline. Total unprocessed meat consumption was estimated as the sum
      of unprocessed red meat (beef, pork, and organ meat) and poultry consumption. In
      the fully adjusted Cox regression model, the relative risks of CVD across
      increasing quintiles of total unprocessed meat intake were 1.0 (reference), 0.72
      (95% confidence interval (CI): 0.55, 0.95), 0.57 (95% CI: 0.42, 0.78), 0.69 (95%
      CI: 0.51, 0.95), and 0.69 (95% CI: 0.48, 0.97), but no significant linear trend
      was detected (p for trend = 0.14). Frequent poultry consumption was significantly
      associated with a decreased CVD risk; this association showed a dose-response
      relationship (p for trend = 0.04). This study showed that a moderate intake of
      total unprocessed meat was inversely associated with CVD risk. A significant
      inverse association between poultry consumption and incident CVD was observed in
      Korean adults, requiring further confirmation in other populations.

PMID- 28505127
TI  - Variability of DNA Methylation within Schizophrenia Risk Loci across Subregions
      of Human Hippocampus.
AB  - Identification of 108 genomic regions significantly associated with schizophrenia
      risk by the Psychiatric Genomics Consortium was a milestone for the field, and
      much work is now focused on determining the mechanism of risk associated with
      each locus. Within these regions, we investigated variability of DNA methylation,
      a low-level cellular phenotype closely linked to genotype, in two highly similar
      cellular populations sampled from the human hippocampus, to draw inferences about
      the elaboration of genotype to phenotype within these loci enriched for
      schizophrenia risk. DNA methylation was assessed with the Illumina
      HumanMethylation450 BeadArray in tissue laser-microdissected from the stratum
      oriens of subfield CA1 or CA2/3, regions having unique connectivity with
      intrinsic and extrinsic fiber systems within the hippocampus. Samples consisted
      of postmortem human hippocampus tissue from eight schizophrenia patients, eight
      bipolar disorder patients, and eight healthy control subjects. Within these
      genomic regions, we observed far greater difference in methylation patterns
      between circuit locations within subjects than in a single subregion between
      subjects across diagnostic groups, demonstrating the complexity of genotype to
      phenotype elaboration across the diverse circuitry of the human brain.

PMID- 28505129
TI  - Assessment of Antimicrobial and Antioxidant Activities of Nepeta trachonitica:
      Analysis of Its Phenolic Compounds Using HPLC-MS/MS.
AB  - Continuing our work on the sources of natural bioactive compounds, we evaluated
      the antimicrobial and antioxidant activities of Nepeta trachonitica as well as
      its major phenolic content using the high-performance liquid chromatography-mass
      spectrometry/mass spectrometry (HPLC-MS/MS) technique. For antioxidant activity,
      ferric reducing antioxidant power (FRAP) and cupric ion reducing antioxidant
      capacity (CUPRAC) methods were performed to measure the reducing power and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) assay was employed to evaluate the radical
      scavenging activity of the sample. For antimicrobial activity, three Gram
      positive and four Gram-negative microbial species as well as three fungi species
      were tested. N. trachonitica appeared to have reasonable antioxidant activity and
      decent antimicrobial activity as indicated by the inhibition of the organisms'
      growth. The most susceptible species were Bacillus subtilis ATCC 6633 and
      Escherichia coli ATCC 11229 among the organisms tested. Ethanol extract of the
      plant has the highest effect on Saccharomyces cerevisiae but no effect on
      Yarrowia lipolytica. The HPLC-MS/MS analysis showed that at least 11 major
      phenolic compounds of N. trachonitica exist, the major ones being rosmarinic
      acid, chlorogenic acid and quinic acid. The obtained results suggest that N.
      trachonitica could be a promising source for food and nutraceutical industries
      because of its antimicrobial and antioxidant properties and phenolic compounds.

PMID- 28505130
TI  - A Review of Microwave Thermography Nondestructive Testing and Evaluation.
AB  - Microwave thermography (MWT) has many advantages including strong penetrability,
      selective heating, volumetric heating, significant energy savings, uniform
      heating, and good thermal efficiency. MWT has received growing interest due to
      its potential to overcome some of the limitations of microwave nondestructive
      testing (NDT) and thermal NDT. Moreover, during the last few decades MWT has
      attracted growing interest in materials assessment. In this paper, a
      comprehensive review of MWT techniques for materials evaluation is conducted
      based on a detailed literature survey. First, the basic principles of MWT are
      described. Different types of MWT, including microwave pulsed thermography,
      microwave step thermography, microwave pulsed phase thermography, and microwave
      lock-in thermography are defined and introduced. Then, MWT case studies are
      discussed. Next, comparisons with other thermography and NDT methods are
      conducted. Finally, the trends in MWT research are outlined, including new
      theoretical studies, simulations and modelling, signal processing algorithms,
      internal properties characterization, automatic separation and inspection
      systems. This work provides a summary of MWT, which can be utilized for material
      failures prevention and quality control.

PMID- 28505131
TI  - Reduction of the Influence of Laser Beam Directional Dithering in a Laser
      Triangulation Displacement Probe.
AB  - Directional dithering of a laser beam potentially limits the detection accuracy
      of a laser triangulation displacement probe. A theoretical analysis indicates
      that the measurement accuracy will linearly decrease as the laser dithering angle
      increases. To suppress laser dithering, a scheme for reduction of the influence
      of laser beam directional dithering in a laser triangulation displacement probe,
      which consists of a collimated red laser, a laser beam pointing control setup, a
      receiver lens, and a charge-coupled device, is proposed in this paper. The laser
      beam pointing control setup is inserted into the source laser beam and the
      measured object and can separate the source laser beam into two symmetrical laser
      beams. Hence, at the angle at which the source laser beam dithers, the positional
      averages of the two laser spots are equal and opposite. Moreover, a virtual
      linear function method is used to maintain a stable average of the positions of
      the two spots on the imaging side. Experimental results indicate that with laser
      beam pointing control, the estimated standard deviation of the fitting error
      decreases from 0.3531 mm to 0.0100 mm , the repeatability accuracy can be lowered
      from +/-7 mm to +/-5 MU m , and the nonlinear error can be reduced from +/-6 % FS
      (full scale) to +/-0.16 % FS.

PMID- 28505132
TI  - Preparation and Characterization of Chitosan Obtained from Shells of Shrimp
      (Litopenaeus vannamei Boone).
AB  - The main source of commercial chitosan is the extensive deacetylation of its
      parent polymer chitin. It is present in green algae, the cell walls or fungi and
      in the exoskeleton of crustaceans. A novel procedure for preparing chitosan from
      shrimp shells was developed. The procedure involves two 10-minutes bleaching
      steps with ethanol after the usual demineralization and deproteinization
      processes. Before deacetylation, chitin was immersed in 12.5 M NaOH, cooled down
      and kept frozen for 24 h. The obtained chitosan was characterized using scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), UV, X
      ray diffraction (XRD) and viscosimetry. Samples of white chitosan with
      acetylation degrees below 9 % were obtained, as determined by FTIR and UV-first
      derivative spectroscopy. The change in the morphology of samples was followed by
      SEM. The ash content of chitosan samples were all below 0.063 % . Chitosan was
      soluble in 1 % acetic acid with insoluble contents of 0.62 % or less. XRD
      patterns exhibited the characteristic peaks of chitosan centered at 10 and 20
      degrees in 2 theta . The molecular weight of chitosan was between 2.3 and 2.8 *
      10 5 g/mol. It is concluded that the procedure developed in the present work
      allowed obtaining chitosans with physical and chemical properties suitable for
      pharmaceutical applications.

PMID- 28505133
TI  - Macronutrient Intake and Risk of Crohn's Disease: Systematic Review and Dose
      Response Meta-Analysis of Epidemiological Studies.
AB  - Dietary intake is potentially associated with the onset of Crohn's disease (CD),
      but evidence from epidemiological studies has remained unclear. This study aimed
      to evaluate the role of macronutrient intake in the development of CD. A
      systematic search was conducted in PubMed and Web of Science to identify all
      relevant studies, and the role of macronutrients in the development of CD was
      quantitatively assessed by dose-response meta-analysis. Four case-control studies
      (a total of 311 CD cases and 660 controls) and five prospective cohort studies
      (238,887 participants and 482 cases) were identified. The pooled relative risks
      (RR) for per 10 g increment/day were 0.991 (95% confidence interval (CI): 0.978
      1.004) for total carbohydrate intake, 1.018 (95% CI: 0.969-1.069) for total fat
      intake, and 1.029 (95% CI: 0.955-1.109) for total protein intake. Fiber intake
      was inversely associated with CD risk (RR for per 10 g increment/day: 0.853, 95%
      CI: 0.762-0.955), but the association was influenced by study design and smoking
      adjustment. In subtypes, sucrose intake was positively related with CD risk (RR
      for per 10 g increment/day: 1.088, 95% CI: 1.020-1.160). Non-linear dose-response
      association was also found between fiber and sucrose intake and CD risk. In
      conclusion, this meta-analysis suggested a lack of association between total
      carbohydrate, fat or protein intake and the risk of CD, while high fiber intake
      might decrease the risk. In subtypes, high sucrose intake might increase the risk
      of CD.

PMID- 28505135
TI  - Sea Ice Detection Based on an Improved Similarity Measurement Method Using
      Hyperspectral Data.
AB  - Hyperspectral remote sensing technology can acquire nearly continuous spectrum
      information and rich sea ice image information, thus providing an important means
      of sea ice detection. However, the correlation and redundancy among hyperspectral
      bands reduce the accuracy of traditional sea ice detection methods. Based on the
      spectral characteristics of sea ice, this study presents an improved similarity
      measurement method based on linear prediction (ISMLP) to detect sea ice. First,
      the first original band with a large amount of information is determined based on
      mutual information theory. Subsequently, a second original band with the least
      similarity is chosen by the spectral correlation measuring method. Finally,
      subsequent bands are selected through the linear prediction method, and a support
      vector machine classifier model is applied to classify sea ice. In experiments
      performed on images of Baffin Bay and Bohai Bay, comparative analyses were
      conducted to compare the proposed method and traditional sea ice detection
      methods. Our proposed ISMLP method achieved the highest classification accuracies
      (91.18% and 94.22%) in both experiments. From these results the ISMLP method
      exhibits better performance overall than other methods and can be effectively
      applied to hyperspectral sea ice detection.

PMID- 28505128
TI  - A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in
      Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on
      Prognostic Factors and Personalised Medicine.
AB  - Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative
      colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis,
      psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune
      mediated uveitis, are treated with biologics targeting the pro-inflammatory
      molecule tumour necrosis factor-alpha (TNF) (i.e., TNF inhibitors). Approximately
      one-third of the patients do not respond to the treatment. Genetics and lifestyle
      may affect the treatment results. The aims of this multidisciplinary
      collaboration are to identify (1) molecular signatures of prognostic value to
      help tailor treatment decisions to an individual likely to initiate TNF inhibitor
      therapy, followed by (2) lifestyle factors that support achievement of optimised
      treatment outcome. This report describes the establishment of a cohort that aims
      to obtain this information. Clinical data including lifestyle and treatment
      response and biological specimens (blood, faeces, urine, and, in IBD patients,
      intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy.
      Both hypothesis-driven and data-driven analyses will be performed according to
      pre-specified protocols including pathway analyses resulting from candidate gene
      expression analyses and global approaches (e.g., metabolomics, metagenomics,
      proteomics). The final purpose is to improve the lives of patients suffering from
      CIDs, by providing tools facilitating treatment selection and dietary
      recommendations likely to improve the clinical outcome.

PMID- 28505134
TI  - A Novel Roseosiphophage Isolated from the Oligotrophic South China Sea.
AB  - The Roseobacter clade is abundant and widespread in marine environments and plays
      an important role in oceanic biogeochemical cycling. In this present study, a
      lytic siphophage (labeled vB_DshS-R5C) infecting the strain type of
      Dinoroseobacter shibae named DFL12T, which is part of the Roseobacter clade, was
      isolated from the oligotrophic South China Sea. Phage R5C showed a narrow host
      range, short latent period and low burst size. The genome length of phage R5C was
      77, 874 bp with a G+C content of 61.5%. Genomic comparisons detected no genome
      matches in the GenBank database and phylogenetic analysis based on DNA polymerase
      I revealed phylogenetic features that were distinct to other phages, suggesting
      the novelty of R5C. Several auxiliary metabolic genes (e.g., phoH gene, heat
      shock protein and queuosine biosynthesis genes) were identified in the R5C genome
      that may be beneficial to the host and/or offer a competitive advantage for the
      phage. Among siphophages infecting the Roseobacter clade (roseosiphophages), four
      gene transfer agent-like genes were commonly located with close proximity to
      structural genes, suggesting that their function may be related to the tail of
      siphoviruses. The isolation and characterization of R5C demonstrated the high
      genomic and physiological diversity of roseophages as well as improved our
      understanding of host-phage interactions and the ecology of the marine
      Roseobacter.

PMID- 28505137
TI  - Airborne Infrared and Visible Image Fusion Combined with Region Segmentation.
AB  - This paper proposes an infrared (IR) and visible image fusion method introducing
      region segmentation into the dual-tree complex wavelet transform (DTCWT) region.
      This method should effectively improve both the target indication and scene
      spectrum features of fusion images, and the target identification and tracking
      reliability of fusion system, on an airborne photoelectric platform. The method
      involves segmenting the region in an IR image by significance, and identifying
      the target region and the background region; then, fusing the low-frequency
      components in the DTCWT region according to the region segmentation result. For
      high-frequency components, the region weights need to be assigned by the
      information richness of region details to conduct fusion based on both weights
      and adaptive phases, and then introducing a shrinkage function to suppress noise;
      Finally, the fused low-frequency and high-frequency components are reconstructed
      to obtain the fusion image. The experimental results show that the proposed
      method can fully extract complementary information from the source images to
      obtain a fusion image with good target indication and rich information on scene
      details. They also give a fusion result superior to existing popular fusion
      methods, based on eithers subjective or objective evaluation. With good stability
      and high fusion accuracy, this method can meet the fusion requirements of IR
      visible image fusion systems.

PMID- 28505136
TI  - Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with
      Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.
AB  - Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our
      hospital, has shown beneficial effects in cancer patients. In this study, we
      investigated the molecular mechanisms underlying the beneficial effects of GYII
      on murine breast cancer models. GYII showed significant inhibitory effects on
      tumor growth and metastasis in the murine breast cancer model. Additionally, GYII
      suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A
      better inhibitory effect on 4T1 cell proliferation and migration was found in the
      decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree
      of angiogenesis were reduced in tumor tissues. Western blot analysis showed
      decreased expression of heparanase and growth factors in the cells treated with
      GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the
      phosphorylation of extracellular signal-regulated kinase (ERK) and serine
      threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth
      and anti-metastatic effects in the murine breast cancer model. The anti-tumor
      activity of GYII and its decomposed recipes is, at least partly, associated with
      decreased heparanase and growth factor expression, which subsequently suppressed
      the activation of the ERK and AKT pathways.

PMID- 28505138
TI  - Estimating Density and Temperature Dependence of Juvenile Vital Rates Using a
      Hidden Markov Model.
AB  - Organisms in the wild have cryptic life stages that are sensitive to changing
      environmental conditions and can be difficult to survey. In this study, I used
      mark-recapture methods to repeatedly survey Anaea aidea (Nymphalidae)
      caterpillars in nature, then modeled caterpillar demography as a hidden Markov
      process to assess if temporal variability in temperature and density influence
      the survival and growth of A. aidea over time. Individual encounter histories
      result from the joint likelihood of being alive and observed in a particular
      stage, and I have included hidden states by separating demography and
      observations into parallel and independent processes. I constructed a demographic
      matrix containing the probabilities of all possible fates for each stage,
      including hidden states, e.g., eggs and pupae. I observed both dead and live
      caterpillars with high probability. Peak caterpillar abundance attracted multiple
      predators, and survival of fifth instars declined as per capita predation rate
      increased through spring. A time lag between predator and prey abundance was
      likely the cause of improved fifth instar survival estimated at high density.
      Growth rates showed an increase with temperature, but the preferred model did not
      include temperature. This work illustrates how state-space models can include
      unobservable stages and hidden state processes to evaluate how environmental
      factors influence vital rates of cryptic life stages in the wild.

PMID- 28505140
TI  - Self-Management Group Exercise Extends Healthy Life Expectancy in Frail Community
      Dwelling Older Adults.
AB  - Preventing frailty and its adverse health outcomes is crucial in countries with a
      large elderly population, such as Japan. Since the long-term care insurance
      (LTCI) system was launched, the number of certified older adults with LTCI
      service requirement has continued to increase. This is a serious problem, because
      the LTCI service requirement certification is equivalent to disability. The aim
      of this study was to evaluate the effect of a self-management group intervention
      on new LTCI service requirement certifications in community-dwelling older adults
      in Japan. We analyzed the cohort data from a prospective study. In this study, we
      recruited community-dwelling adults aged 65 years and older who were independent
      in a city in Kyoto prefecture in 2012. The subjects in the participation group (n
      = 1620) attended 60-min group training sessions once or twice every two weeks
      from December 2012 to December 2016. The exercise sessions consisted of mild
      intensity aerobic exercise, mild strength training, flexibility and balance
      exercises, and cool-down activities. These exercise classes were facilitated by
      well-trained volunteer staff. The outcome measure was the number of new LTCI
      requirement certifications during a four-year follow-up period. During the four
      year follow-up period, 247 subjects (15.2%) in the participation group and 334
      (20.6%) in the control group were newly certified for LTCI service requirements.
      The hazard ratio for new LTCI service requirements in the participation group
      compared with the control group was 0.73 (95% CI = 0.62-0.86) in the four-year
      follow-up period. These results indicate the usefulness of self-management group
      exercise to reduce the incidence of disability in older adults. Thus, increasing
      self-management group activities in each community should be encouraged.

PMID- 28505139
TI  - Mental Health Problems and Related Factors in Ecuadorian College Students.
AB  - Although the mental health problems of college students have been the subject of
      increasing research, there are no studies about its prevalence in Ecuadorian
      college students. The aim of this study was to determine the mental health
      problems and their associated factors in Ecuadorian freshmen university students.
      A sample of 1092 students (53.7% women; mean age = 18.3 years) were recruited
      from the Technical Particular University of Loja (Ecuador). Socio-demographic,
      academic, and clinical characteristics were gathered, as well as information on
      the participants' mental health through a number of mental health screens.
      Prevalence of positive screens was 6.2% for prevalence of major depressive
      episodes, 0.02% for generalized anxiety disorders, 2.2% for panic disorders,
      32.0% for eating disorders, 13.1% for suicidal risk. Mental health problems were
      significantly associated with sex, area of study, self-esteem, social support,
      personality and histories of mental health problems. The findings offer a
      starting point for identifying useful factors to target prevention and
      intervention strategies aimed at university students.

PMID- 28505141
TI  - A Decade of Progress toward Ending the Intensive Confinement of Farm Animals in
      the United States.
AB  - In this paper, the Humane Society of the United States (HSUS) farm animal
      protection work over the preceding decade is described from the perspective of
      the organization. Prior to 2002, there were few legal protections for animals on
      the farm, and in 2005, a new campaign at the HSUS began to advance state ballot
      initiatives throughout the country, with a decisive advancement in California
      (Proposition 2) that paved the way for further progress. Combining legislative
      work with undercover farm and slaughterhouse investigations, litigation and
      corporate engagement, the HSUS and fellow animal protection organizations have
      made substantial progress in transitioning the veal, pork and egg industries away
      from intensive confinement systems that keep the animals in cages and crates.
      Investigations have become an important tool for demonstrating widespread
      inhumane practices, building public support and convincing the retail sector to
      publish meaningful animal welfare policies. While federal legislation protecting
      animals on the farm stalled, there has been steady state-by-state progress, and
      this is complemented by major brands such as McDonald's and Walmart pledging to
      purchase only from suppliers using cage-free and crate-free animal housing
      systems. The evolution of societal expectations regarding animals has helped
      propel the recent wave of progress and may also be driven, in part, by the work
      of animal protection organizations.

PMID- 28505142
TI  - Mitochondria Targeting with Luminescent Rhenium(I) Complexes.
AB  - Two new neutral fac-[Re(CO)3(phen)L] compounds (1,2), with phen = 1,10
      phenanthroline and L = O2C(CH2)5CH3 or O2C(CH2)4C=CH, were synthetized in one-pot
      procedures from fac-[Re(CO)3(phen)Cl] and the corresponding carboxylic acids, and
      were fully characterized by IR and UV-Vis absorption spectroscopy, 1H- and 13C
      NMR, mass spectrometry and X-ray crystallography. The compounds, which display
      orange luminescence, were used as probes for living cancer HeLa cell staining.
      Confocal microscopy revealed accumulation of both dyes in mitochondria. To
      investigate the mechanism of mitochondrial staining, a new non-emissive compound,
      fac-[Re(CO)3(phen)L], with L = O2C(CH2)3((C5H5)Fe(C5H4), i.e., containing a
      ferrocenyl moiety, was synthetized and characterized (3). 3 shows the same
      mitochondrial accumulation pattern as 1 and 2. Emission of 3 can only be possible
      when ferrocene-containing ligand dissociates from the metal center to produce a
      species containing the luminescent fac-[Re(CO)3(phen)]+ core. The release of
      ligands from the Re center was verified in vitro through the conjugation with
      model proteins. These findings suggest that the mitochondria accumulation of
      compounds 1-3 is due to the formation of luminescent fac-[Re(CO)3(phen)]+
      products, which react with cellular matrix molecules giving secondary products
      and are uptaken into the negatively charged mitochondrial membranes. Thus,
      reported compounds feature a rare dissociation-driven mechanism of action with
      great potential for biological applications.

PMID- 28505144
TI  - Microbiota and Particulate Matter Assessment in Portuguese Optical Shops
      Providing Contact Lens Services.
AB  - The aim of this work was to assess the microbiota (fungi and bacteria) and
      particulate matter in optical shops, contributing to a specific protocol to
      ensure a proper assessment. Air samples were collected through an impaction
      method. Surface and equipment swab samples were also collected side-by-side.
      Measurements of particulate matter were performed using portable direct-reading
      equipment. A walkthrough survey and checklist was also applied in each shop.
      Regarding air sampling, eight of the 13 shops analysed were above the legal
      requirement and 10 from the 26 surfaces samples were overloaded. In three out of
      the 13 shops fungal contamination in the analysed equipment was not detected. The
      bacteria air load was above the threshold in one of the 13 analysed shops.
      However, bacterial counts were detected in all sampled equipment. Fungi and
      bacteria air load suggested to be influencing all of the other surface and
      equipment samples. These results reinforce the need to improve air quality, not
      only to comply with the legal requirements, but also to ensure proper hygienic
      conditions. Public health intervention is needed to assure the quality and safety
      of the rooms and equipment in optical shops that perform health interventions in
      patients.

PMID- 28505143
TI  - The Transcriptome of Type I Murine Astrocytes under Interferon-Gamma Exposure and
      Remyelination Stimulus.
AB  - Astrocytes are considered to be an important contributor to central nervous
      system (CNS) disorders, particularly multiple sclerosis. The transcriptome of
      these cells is greatly affected by cytokines released by lymphocytes, penetrating
      the blood-brain barrier-in particular, the classical pro-inflammatory cytokine
      interferon-gamma (IFNgamma). We report here the transcriptomal profiling of
      astrocytes treated using IFNgamma and benztropine, a putative remyelinization
      agent. Our findings indicate that the expression of genes involved in antigen
      processing and presentation in astrocytes are significantly upregulated upon
      IFNgamma exposure, emphasizing the critical role of this cytokine in the
      redirection of immune response towards self-antigens. Data reported herein
      support previous observations that the IFNgamma-induced JAK-STAT signaling
      pathway may be regarded as a valuable target for pharmaceutical interventions.

PMID- 28505145
TI  - DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated
      with Survival Outcomes in Breast Cancer Patients.
AB  - Early postnatal exposures to Bisphenol A (BPA) and genistein (GEN) have been
      reported to predispose for and against mammary cancer, respectively, in adult
      rats. Since the changes in cancer susceptibility occurs in the absence of the
      original chemical exposure, we have investigated the potential of epigenetics to
      account for these changes. DNA methylation studies reveal that prepubertal BPA
      exposure alters signaling pathways that contribute to carcinogenesis. Prepubertal
      exposure to GEN and BPA + GEN revealed pathways involved in maintenance of
      cellular function, indicating that the presence of GEN either reduces or counters
      some of the alterations caused by the carcinogenic properties of BPA. We
      subsequently evaluated the potential of epigenetic changes in the rat mammary
      tissues to predict survival in breast cancer patients via the Cancer Genomic
      Atlas (TCGA). We identified 12 genes that showed strong predictive values for
      long-term survival in estrogen receptor positive patients. Importantly, two genes
      associated with improved long term survival, HPSE and RPS9, were identified to be
      hypomethylated in mammary glands of rats exposed prepuberally to GEN or to GEN +
      BPA respectively, reinforcing the suggested cancer suppressive properties of GEN.

PMID- 28505146
TI  - Upregulated Autophagy in Sertoli Cells of Ethanol-Treated Rats Is Associated with
      Induction of Inducible Nitric Oxide Synthase (iNOS), Androgen Receptor
      Suppression and Germ Cell Apoptosis.
AB  - This study was conducted to investigate the autophagic response of Sertoli cells
      (SCs) to acute ethanol toxicity using in vivo and in vitro models. Adult Wistar
      rats were intraperitoneally injected with either 5 g/kg ethanol or phosphate
      buffered saline (for the control group) and sacrificed 0, 3, 6 and 24 h after
      injection. Compared to the control group, enhanced germ cell apoptosis was
      observed in the ethanol-treated rats (ETRs) in association with upregulation of
      iNOS and reduced expression of androgen receptor protein levels in SCs, which
      were resistant to apoptosis. Meanwhile, autophagy was upregulated in ETR SCs
      (peaking at 24 h) compared to the control group, as evidenced by transcription
      factor EB (TFEB) nuclear translocation, enhanced expression of microtubule
      associated protein 1 light chain3-II (LC3-II), lysosome-associated membrane
      protein-2 (LAMP-2), pan cathepsin protein levels and reduced expression of p62.
      This upregulation of SC autophagy was confirmed ultrastructurally by enhanced
      formation of autophagic vacuoles and by immunofluorescent double labelling of
      autophagosomal and lysosomal markers. Study of cultured SCs confirmed enhanced
      autophagic response to ethanol toxicity, which was cytoprotective based on
      decreased viability of SCs upon blocking autophagy with 3-methyladenine (3-MA).
      The results highlighted the molecular mechanisms of prosurvival autophagy in ETR
      SCs for the first time, and may have significant implications for male fertility.

PMID- 28505147
TI  - Changes in the Sodium Content of Australian Processed Foods between 1980 and 2013
      Using Analytical Data.
AB  - The objective of this study was to obtain analytical data on the sodium content
      of a range of processed foods and compare the levels obtained with their label
      claims and with published data of the same or equivalent processed foods in the
      1980s and 1990s to investigate the extent of any change in sodium content in
      relation to reformulation targets. The sodium contents of 130 Australian
      processed foods were obtained by inductively coupled plasma optical emission
      spectrometry (ICP-OES) analysis and compared with previously published data. The
      sodium content between 1980 and 2013 across all products and by each product
      category were compared. There was a significant overall sodium reduction of 23%,
      181 mg/100 g (p <0.001, 95% CI (Confidence Interval), 90 to 272 mg/100 g), in
      Australian processed foods since 1980, with a 12% (83 mg/100 g) reduction over
      the last 18 years. The sodium content of convenience foods (p < 0.001, 95% CI, 94
      to 291 mg/100 g) and snack foods (p = 0.017, 95% CI, 44 to 398 mg/100 g) had
      declined significantly since 1980. Meanwhile, the sodium contents of processed
      meats (p = 0.655, 95% CI, -121 to 190) and bread and other bakery products (p =
      0.115, 95% CI, -22 to 192) had decreased, though not significantly. Conversely,
      the sodium content of cheese (p = 0.781, 95% CI, -484 to 369 mg/100 g) had
      increased but also not significantly. Of the 130 products analysed, 62% met
      Australian reformulation targets. Sodium contents of the processed foods and the
      overall changes in comparison with previous data indicate a decrease over the 33
      years period and suggest that the Australian recommended reformulation targets
      have been effective. Further sodium reduction of processed foods is still
      required and continuous monitoring of the reduction of sodium levels in processed
      foods is needed.

PMID- 28505148
TI  - Potential Pathogenesis and Biomarkers of Kidney Cancer-Related Stroke.
AB  - BACKGROUND Stroke risk and stroke recurrence are increased in cancer patients,
      but the pathogenesis and biomarkers of kidney cancer-related stroke (KCS) are
      generally unclear. The aim of the present research was to investigate the
      pathogenesis and plasma biomarkers of kidney cancer-related stroke. MATERIAL AND
      METHODS A retrospective review was conducted on acute stroke patients with kidney
      cancer (KC) who were admitted to the hospital between January 2006 and December
      2015. A total of 106 patients with KCS (active KC patients with acute stroke but
      without conventional vascular risks) were identified. In addition, 106 age- and
      sex-matched patients with KC alone were recruited. RESULTS KCS patients had
      higher plasma D-dimer, cancer antigen (CA) 125, and CEA levels and greater
      proteinuria levels than did KC patients. Multiple logistic regression analysis
      showed that the risk of stroke in patients with KC increased independently by
      0.8% (odds ratio [OR] 1.008; 95% confidence interval [CI] 1.002, 1.013; p=0.004)
      with a 1 ng/mL increase in D-dimer levels, by 1.2% (OR 1.012; 95% CI 1.007,
      1.018; p=0.000) with a 1 U/mL increase in CA125, by 2.5% (OR 1.025; 95% CI 1.012,
      1.038; p=0.000) with a 1 U/mL increase in CEA by 1.4% (OR 1.014; 95% CI 1.005,
      1.024; p=0.004) with a 1 mg increase in urine protein in 24 hours. CONCLUSIONS
      Elevated plasma D-dimer, CA125 and CEA levels, and increased urine protein levels
      might lead to hypercoagulability and then KCS; however, they may also be
      biomarkers of KCS.

PMID- 28505149
TI  - Distinct DNA-binding surfaces in the ATPase and linker domains of MutLgamma
      determine its substrate specificities and exert separable functions in meiotic
      recombination and mismatch repair.
AB  - Mlh1-Mlh3 (MutLgamma) is a mismatch repair factor with a central role in
      formation of meiotic crossovers, presumably through resolution of double Holliday
      junctions. MutLgamma has DNA-binding, nuclease, and ATPase activities, but how
      these relate to one another and to in vivo functions are unclear. Here, we
      combine biochemical and genetic analyses to characterize Saccharomyces cerevisiae
      MutLgamma. Limited proteolysis and atomic force microscopy showed that purified
      recombinant MutLgamma undergoes ATP-driven conformational changes. In vitro,
      MutLgamma displayed separable DNA-binding activities toward Holliday junctions
      (HJ) and, surprisingly, single-stranded DNA (ssDNA), which was not predicted from
      current models. MutLgamma bound DNA cooperatively, could bind multiple substrates
      simultaneously, and formed higher-order complexes. FeBABE hydroxyl radical
      footprinting indicated that the DNA-binding interfaces of MutLgamma for ssDNA and
      HJ substrates only partially overlap. Most contacts with HJ substrates were
      located in the linker regions of MutLgamma, whereas ssDNA contacts mapped within
      linker regions as well as the N-terminal ATPase domains. Using yeast genetic
      assays for mismatch repair and meiotic recombination, we found that mutations
      within different DNA-binding surfaces exert separable effects in vivo. For
      example, mutations within the Mlh1 linker conferred little or no meiotic
      phenotype but led to mismatch repair deficiency. Interestingly, mutations in the
      N-terminal domain of Mlh1 caused a stronger meiotic defect than mlh1Delta,
      suggesting that the mutant proteins retain an activity that interferes with
      alternative recombination pathways. Furthermore, mlh3Delta caused more chromosome
      missegregation than mlh1Delta, whereas mlh1Delta but not mlh3Delta partially
      alleviated meiotic defects of msh5Delta mutants. These findings illustrate
      functional differences between Mlh1 and Mlh3 during meiosis and suggest that
      their absence impinges on chromosome segregation not only via reduced formation
      of crossovers. Taken together, our results offer insights into the structure
      function relationships of the MutLgamma complex and reveal unanticipated genetic
      relationships between components of the meiotic recombination machinery.

PMID- 28505150
TI  - A question of fate.
AB  - Ever since the discovery of neural stem cells in the mammalian brain, the
      possibility of brain tissue regeneration has captured the minds of scientists,
      clinicians, and the public. Neural stem cells have been envisioned as a source of
      donor cells for transplantation and vectors for the delivery of gene therapy.
      Over the past decade, many researchers have contributed to characterizing these
      cells and their lineages, providing the foundation for their utilization as
      therapeutic devices. In a new study, Azim and colleagues took a different
      approach: using pharmacogenomics to focus on neural stem cell lineage, they
      identified specific compounds that can direct neural stem cell fate toward a
      specific lineage in vivo, both in physiological and pathological conditions.
      Their work opens new avenues for treatment of neurodegenerative and demyelinating
      disorders.

PMID- 28505151
TI  - Mixture models reveal multiple positional bias types in RNA-Seq data and lead to
      accurate transcript concentration estimates.
AB  - Accuracy of transcript quantification with RNA-Seq is negatively affected by
      positional fragment bias. This article introduces Mix2 (rd. "mixquare"), a
      transcript quantification method which uses a mixture of probability
      distributions to model and thereby neutralize the effects of positional fragment
      bias. The parameters of Mix2 are trained by Expectation Maximization resulting in
      simultaneous transcript abundance and bias estimates. We compare Mix2 to
      Cufflinks, RSEM, eXpress and PennSeq; state-of-the-art quantification methods
      implementing some form of bias correction. On four synthetic biases we show that
      the accuracy of Mix2 overall exceeds the accuracy of the other methods and that
      its bias estimates converge to the correct solution. We further evaluate Mix2 on
      real RNA-Seq data from the Microarray and Sequencing Quality Control (MAQC, SEQC)
      Consortia. On MAQC data, Mix2 achieves improved correlation to qPCR measurements
      with a relative increase in R2 between 4% and 50%. Mix2 also yields repeatable
      concentration estimates across technical replicates with a relative increase in
      R2 between 8% and 47% and reduced standard deviation across the full
      concentration range. We further observe more accurate detection of differential
      expression with a relative increase in true positives between 74% and 378% for 5%
      false positives. In addition, Mix2 reveals 5 dominant biases in MAQC data
      deviating from the common assumption of a uniform fragment distribution. On SEQC
      data, Mix2 yields higher consistency between measured and predicted concentration
      ratios. A relative error of 20% or less is obtained for 51% of transcripts by
      Mix2, 40% of transcripts by Cufflinks and RSEM and 30% by eXpress. Titration
      order consistency is correct for 47% of transcripts for Mix2, 41% for Cufflinks
      and RSEM and 34% for eXpress. We, further, observe improved repeatability across
      laboratory sites with a relative increase in R2 between 8% and 44% and reduced
      standard deviation.

PMID- 28505152
TI  - A predictive coding account of bistable perception - a model-based fMRI study.
AB  - In bistable vision, subjective perception wavers between two interpretations of a
      constant ambiguous stimulus. This dissociation between conscious perception and
      sensory stimulation has motivated various empirical studies on the neural
      correlates of bistable perception, but the neurocomputational mechanism behind
      endogenous perceptual transitions has remained elusive. Here, we recurred to a
      generic Bayesian framework of predictive coding and devised a model that casts
      endogenous perceptual transitions as a consequence of prediction errors emerging
      from residual evidence for the suppressed percept. Data simulations revealed
      close similarities between the model's predictions and key temporal
      characteristics of perceptual bistability, indicating that the model was able to
      reproduce bistable perception. Fitting the predictive coding model to behavioural
      data from an fMRI-experiment on bistable perception, we found a correlation
      across participants between the model parameter encoding perceptual stabilization
      and the behaviourally measured frequency of perceptual transitions, corroborating
      that the model successfully accounted for participants' perception. Formal model
      comparison with established models of bistable perception based on mutual
      inhibition and adaptation, noise or a combination of adaptation and noise was
      used for the validation of the predictive coding model against the established
      models. Most importantly, model-based analyses of the fMRI data revealed that
      prediction error time-courses derived from the predictive coding model correlated
      with neural signal time-courses in bilateral inferior frontal gyri and anterior
      insulae. Voxel-wise model selection indicated a superiority of the predictive
      coding model over conventional analysis approaches in explaining neural activity
      in these frontal areas, suggesting that frontal cortex encodes prediction errors
      that mediate endogenous perceptual transitions in bistable perception. Taken
      together, our current work provides a theoretical framework that allows for the
      analysis of behavioural and neural data using a predictive coding perspective on
      bistable perception. In this, our approach posits a crucial role of prediction
      error signalling for the resolution of perceptual ambiguities.

PMID- 28505153
TI  - Gene duplication and co-evolution of G1/S transcription factor specificity in
      fungi are essential for optimizing cell fitness.
AB  - Transcriptional regulatory networks play a central role in optimizing cell
      survival. How DNA binding domains and cis-regulatory DNA binding sequences have
      co-evolved to allow the expansion of transcriptional networks and how this
      contributes to cellular fitness remains unclear. Here we experimentally explore
      how the complex G1/S transcriptional network evolved in the budding yeast
      Saccharomyces cerevisiae by examining different chimeric transcription factor
      (TF) complexes. Over 200 G1/S genes are regulated by either one of the two TF
      complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and
      MCB, respectively. The difference in size and complexity of the G1/S
      transcriptional network across yeast species makes it well suited to investigate
      how TF paralogs (SBF and MBF) and DNA binding sequences (SCB and MCB) co-evolved
      after gene duplication to rewire and expand the network of G1/S target genes. Our
      data suggests that whilst SBF is the likely ancestral regulatory complex, the
      ancestral DNA binding element is more MCB-like. G1/S network expansion took place
      by both cis- and trans- co-evolutionary changes in closely related but distinct
      regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD)
      with that from more distantly related fungi leads to a contraction of the SBF
      regulated G1/S network in budding yeast, which also correlates with increased
      defects in cell growth, cell size, and proliferation.

PMID- 28505154
TI  - Dissecting the human serum antibody response to secondary dengue virus
      infections.
AB  - Dengue viruses (DENVs) are mosquito-borne flaviviruses and the causative agents
      of dengue fever and dengue hemorrhagic fever. As there are four serotypes of DENV
      (DENV1-4), people can be infected multiple times, each time with a new serotype.
      Primary infections stimulate antibodies that mainly neutralize the serotype of
      infection (type-specific), whereas secondary infections stimulate responses that
      cross-neutralize 2 or more serotypes. Previous studies have demonstrated that
      neutralizing antibodies induced by primary infections recognize tertiary and
      quaternary structure epitopes on the viral envelope (E) protein that are unique
      to each serotype. The goal of the current study was to determine the properties
      of neutralizing antibodies induced after secondary infection with a different
      (heterotypic) DENV serotypes. We evaluated whether polyclonal neutralizing
      antibody responses after secondary infections consist of distinct populations of
      type-specific antibodies to each serotype encountered or a new population of
      broadly cross-neutralizing antibodies. We observed two types of responses: in
      some individuals exposed to secondary infections, DENV neutralization was
      dominated by cross-reactive antibodies, whereas in other individuals both type
      specific and cross-reactive antibodies contributed to neutralization. To better
      understand the origins of type-specific and cross-reactive neutralizing
      antibodies, we analyzed sera from individuals with well-documented sequential
      infections with two DENV serotypes only. These individuals had both type-specific
      and cross-reactive neutralizing antibodies to the 2 serotypes responsible for
      infection and only cross-reactive neutralizing antibodies to other serotypes.
      Collectively, the results demonstrate that the quality of neutralizing (and
      presumably protective) antibodies are different in individuals depending on the
      number of previous exposures to different DENV serotypes. We propose a model in
      which low affinity, cross-reactive antibody secreting B-cell clones induced by
      primary exposure evolve during each secondary infection to secrete higher
      affinity and more broadly neutralizing antibodies.

PMID- 28505155
TI  - Oxidative stress and expression of insulin signaling proteins in the brain of
      diabetic rats: Role of Nigella sativa oil and antidiabetic drugs.
AB  - BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of
      type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a
      neuroprotective role against damaging conditions and Alzheimer's progression. The
      present study identifies the mediated emerging effects of the Nigella sativa oil
      (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase
      (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic
      activities. In addition, the possible role of some anti-diabetic drugs in the
      neuro-protection processes and their effect in combination with NSO and/or the
      insulin receptor inhibitor IOMe-AG538 were investigated. METHODS: T2DM-induced
      rats were orally and daily administrated 2.0 ml NSO, 100 mg metformin (MT), 0.8
      mg glimepiride (GI) and different combinations (100 mg MT & 2.0 ml NSO, 0.8 mg GI
      & 2.0 ml NSO and 2.0 ml NSO & intraperitoneal injection of 1/100 LD50 of IOMe
      AG538) per kg body weight for 21 days. RESULTS: A significant increase in the
      brain lipid peroxidation and decrease in the antioxidant status with peripheral
      and central production of pro-inflammatory mediators were observed in diabetes
      induced rats. The brain AChE was activated and associated with diminished brain
      glucose level and cholinergic function. In addition, the brain insulin resistance
      and the attenuated insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3beta) were
      accompanied by an augmentation in GSK-3beta level, which in turn may contribute
      in the extensive alterations of Tau phosphorylation along with changes in PP2A
      level. Furthermore, neuronal loss and elevation in Abeta-42 plaque formation were
      observed due to a low IDE formation and an increased expression of p53, BACE1 and
      APP with diminished ADAM10, SIRT1 and BDNF levels. The expression profile of AD
      related miRNAs in sera and brain tissues displayed its neuro-protection role. The
      treatment of diabetes-induced rats with NSO and the anti-diabetic drugs alone
      and/or in combination have the potential to suppress the oxidative stress, the
      pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the
      insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin
      signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque
      formation and Tau hyper-phosphorylation and restores AD-related miRNA normal
      levels. CONCLUSION: These data suggest that NSO or its combined treatments with
      anti-diabetic drugs have a possible benefit as disease modifying agents for the
      insulin resistance in the brain through enhancing brain insulin signaling
      pathway.

PMID- 28505156
TI  - An independent component analysis confounding factor correction framework for
      identifying broad impact expression quantitative trait loci.
AB  - Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have
      provided numerous insights into the genetics of both gene expression and complex
      diseases. While the majority of eQTL identified in genome-wide analyses impact a
      single gene, eQTL that impact many genes are particularly valuable for network
      modeling and disease analysis. To enable the identification of such broad impact
      eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent
      component analysis. CONFETI is designed to address two conflicting issues when
      searching for broad impact eQTL: the need to account for non-genetic confounding
      factors that can lower the power of the analysis or produce broad impact eQTL
      false positives, and the tendency of methods that account for confounding factors
      to model broad impact eQTL as non-genetic variation. The key advance of the
      CONFETI framework is the use of Independent Component Analysis (ICA) to identify
      variation likely caused by broad impact eQTL when constructing the sample
      covariance matrix used for the random effect in a mixed model. We show that
      CONFETI has better performance than other mixed model confounding factor methods
      when considering broad impact eQTL recovery from synthetic data. We also used the
      CONFETI framework and these same confounding factor methods to identify eQTL that
      replicate between matched twin pair datasets in the Multiple Tissue Human
      Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the
      Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in
      the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both
      cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or
      comparable performance to other mixed model confounding factor analysis methods
      when identifying such eQTL. In these analyses, we were able to identify and
      replicate a few broad impact eQTL although the overall number was small even when
      applying CONFETI. In light of these results, we discuss the broad impact eQTL
      that have been previously reported from the analysis of human data and suggest
      that considerable caution should be exercised when making biological inferences
      based on these reported eQTL.

PMID- 28505157
TI  - Structurally optimized analogs of the retrograde trafficking inhibitor Retro
      2cycl limit Leishmania infections.
AB  - In infected mammalian cells, Leishmania parasites reside within specialized
      compartments called parasitophorous vacuoles (LPVs). We have previously shown
      that Retro-2, a member of a novel class of small retrograde pathway inhibitors
      caused reduced LPV sizes and lower parasite numbers during experimental L.
      mexicana sp. infections. The purpose of this study was to determine if structural
      analogs of Retro-2cycl reported to have superior potency in the inhibition of
      retrograde pathway-dependent phenomena (i.e., polyomavirus cellular infection by
      polyomavrius and Shiga toxin trafficking in cells) are also more effective than
      the parent compound at controlling Leishmania infections. In addition to their
      effects on LPV development, we show that two optimized analogs of Retro-2cycl,
      DHQZ 36 and DHQZ 36.1 limit Leishmania amazonensis infection in macrophages at
      EC50 of 13.63+/-2.58MUM and10.57+/-2.66MUM, respectively, which is significantly
      lower than 40.15MUM the EC50 of Retro-2cycl. In addition, these analogs caused a
      reversal in Leishmania induced suppression of IL-6 release by infected cells
      after LPS activation. Moreover, we show that in contrast to Retro-2cycl that is
      Leishmania static, the analogs can kill Leishmania parasites in axenic cultures,
      which is a desirable attribute for any drug to treat Leishmania infections.
      Together, these studies validate and extend the published structure-activity
      relationship analyses of Retro-2cycl.

PMID- 28505158
TI  - Investigation of the effect of cochlear implant electrode length on speech
      comprehension in quiet and noise compared with the results with users of electro
      acoustic-stimulation, a retrospective analysis.
AB  - OBJECTIVES: This investigation evaluated the effect of cochlear implant (CI)
      electrode length on speech comprehension in quiet and noise and compare the
      results with those of EAS users. METHODES: 91 adults with some degree of residual
      hearing were implanted with a FLEX20, FLEX24, or FLEX28 electrode. Some subjects
      were postoperative electric-acoustic-stimulation (EAS) users; the other subjects
      were in the groups of electric stimulation-only (ES-only). Speech perception was
      tested in quiet and noise at 3 and 6 months of ES or EAS use. Speech
      comprehension results were analyzed and correlated to electrode length. RESULTS:
      While the FLEX20 ES and FLEX24 ES groups were still in their learning phase
      between the 3 to 6 months interval, the FLEX28 ES group was already reaching a
      performance plateau at the three months appointment yielding remarkably high test
      scores. EAS subjects using FLEX20 or FLEX24 electrodes outscored ES-only subjects
      with the same short electrodes on all 3 tests at each interval, reaching
      significance with FLEX20 ES and FLEX24 ES subjects on all 3 tests at the 3-months
      interval and on 2 tests at the 6- months interval. Amongst ES-only subjects at
      the 3- months interval, FLEX28 ES subjects significantly outscored FLEX20 ES
      subjects on all 3 tests and the FLEX24 ES subjects on 2 tests. At the-6 months
      interval, FLEX28 ES subjects still exceeded the other ES-only subjects although
      the difference did not reach significance. CONCLUSIONS: Among ES-only users, the
      FLEX28 ES users had the best speech comprehension scores, at the 3- months
      appointment and tendentially at the 6 months appointment. EAS users showed
      significantly better speech comprehension results compared to ES-only users with
      the same short electrodes.

PMID- 28505159
TI  - Infectious disease ward admission positively influences P. jiroveci pneumonia
      (PjP) outcome: A retrospective analysis of 116 HIV-positive and HIV-negative
      immunocompromised patients.
AB  - P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised
      patients and the factors associated with a bad outcome are poorly understood. A
      retrospective analysis on Pj pneumonia (PjP) cases occurring in Tor Vergata
      University Hospital, Italy, during the period 2011-2015. The patients'
      demographic, clinical and radiological characteristics and the Pj genotypes were
      considered. The study population included 116 patients, 37.9% of whom had
      haematological malignancy or underwent haematological stem cell transplantation
      (HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had
      a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining
      12.1% had a miscellaneous other condition. At univariate analysis, being older
      than 60 years was significantly correlated with a severe PjP (OR [95%CI] 2.52
      [0.10-5.76]; p = 0.031) and death (OR [95%CI] 2.44 [1.05-5.70]; p = 0.036), while
      a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly
      associated with a less severe pneumonia (OR[95%CI] 0.35 [0.15-0.84], p = 0.023);
      moreover, death due to PjP was significantly more frequent in patients with CLD
      (OR[95%CI] 3.26 [1.17-9.05]; p = 0.019) while, admission to the Infectious
      Diseases Unit was significantly associated with fewer deaths (OR[95%CI] 0.10
      [0.03-0.36], p = 0.002). At multivariate analysis, a better PjP outcome was
      observed in patients taking TMP/SMX prophylaxis and that were admitted to the
      Infectious Diseases Unit (OR[95%CI] 0.27 [0.07-1.03], p = 0.055, OR[95%CI] 0.16
      [0.05-0.55]; p = 0.004, respectively). In conclusion, in our study population,
      TMP/SMX prophylaxis and infectious disease specialist approach were variables
      correlated with a better PjP outcome.

PMID- 28505161
TI  - Effect on healthcare utilization and costs of spinal manual therapy for acute low
      back pain in routine care: A propensity score matched cohort study.
AB  - Spinal manual therapy (SMT) is a popular treatment option for low back pain
      (LBP). The aim of our analysis was to evaluate the effects of manual therapy
      delivered by general practitioners and ambulatory orthopedic surgeons in routine
      care on follow up consultations, sick leave, health service utilization and costs
      for acute LBP compared to matched patients not receiving manual therapy. This is
      a propensity score matched cohort study based on health claims data. We
      identified a total of 113.652 adult patients with acute LBP and no coded red
      flags of whom 21.021 (18%) received SMT by physicians. In the final analysis
      17.965 patients in each group could be matched. Balance on patients' coded
      characteristics, comorbidity and prior health service utilization was achieved.
      The provision of SMT for acute LBP had no relevant impact on follow up visits and
      days of sick leave for LBP in the index billing period and the following year.
      SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs.
      23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by
      replacing other health services for LBP. SMT for acute non-specific LBP in
      routine care was not clinically meaningful effective to reduce sick leave and
      reconsultation rates compared to no SMT and did not lead to meaningful savings by
      replacing other health services from the perspective of health insurance. This
      does not imply that SMT is ineffective but might reflect a problem with selection
      of suitable patients and the quality and quantity of SMT in routine care.
      National Manual Medicine societies should state clearly that imaging is not
      routinely needed prior to SMT in patients with low suspicion of presence of red
      flags and monitor the quality of provided services.

PMID- 28505160
TI  - Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid
      leukemia (AML) and the effect of pharmacological inhibition of Nrf2.
AB  - Cytarabine (Ara-C) and Daunorubicin (Dnr) forms the backbone of acute myeloid
      leukemia (AML) therapy. Drug resistance and toxic side effects pose a major
      threat to treatment success and hence alternate less toxic therapies are
      warranted. NF-E2 related factor-2 (Nrf2), a master regulator of antioxidant
      response is implicated in chemoresistance in solid tumors. However, little is
      known about the role of Nrf2 in AML chemoresistance and the effect of
      pharmacological inhibitor brusatol in modulating this resistance. Primary AML
      samples with high ex-vivo IC50 to Ara-C, ATO, Dnr had significantly high NRF2 RNA
      expression. Gene-specific knockdown of NRF2 improved sensitivity to these drugs
      in resistant AML cell lines by decreasing the expression of downstream
      antioxidant targets of Nrf2 by compromising the cell's ability to scavenge the
      ROS. Treatment with brusatol, a pharmacological inhibitor of Nrf2, improved
      sensitivity to Ara-C, ATO, and Dnr and reduced colony formation capacity. AML
      cell lines stably overexpressing NRF2 showed increased resistance to ATO, Dnr and
      Ara-C and increased expression of downstream targets. This study demonstrates
      that Nrf2 could be an ideal druggable target in AML, more so to the drugs that
      function through ROS, suggesting the possibility of using Nrf2 inhibitors in
      combination with chemotherapeutic agents to modulate drug resistance in AML.

PMID- 28505162
TI  - Gender differences in the transmission of risk for antisocial behavior problems
      across generations.
AB  - Previous studies have shown that children of alcohol use disorder (AUD) parents
      are more likely to develop alcohol problems as well as antisocial and other
      behavior problems. The purpose of this study was to examine gender discordance in
      the effect of early maternal and paternal influences on antisocial behaviors of
      boys and girls, as well as the environmental factors that moderate the parental
      effects. Specifically, we examined the effects of childhood and adulthood
      antisocial behavior of the parents on offspring antisocial behavior as young
      adults. We also examined whether mothers' and fathers' drinking problems when
      offspring were young children (6-8 years) affected offspring antisocial behavior
      as young adults (18-21 years). We evaluated 655 children from 339 families in the
      Michigan Longitudinal Study (MLS), a prospective study of AUD and non-AUD
      families. Path models were constructed in order to test for the parental
      contributions to offspring outcomes. We found that both mothers' and fathers'
      antisocial behavior contributed to the children's young adult antisocial
      behavior. Only mothers' drinking problems while their children were little had a
      significant effect on their sons' later drinking, but not on their daughters'.
      These different parental effects suggest that maternal and paternal influences
      may be mediated by different mechanisms.

PMID- 28505165
TI  - Determination of fruit maturity and its prediction model based on the pericarp
      index of absorbance difference (IAD) for peaches.
AB  - Harvest maturity is closely related to peach fruit quality and has a very
      important effect on the fresh fruit market. Unfortunately, at present, it is
      difficult to determine the maturity level of peach fruits by artificial methods.
      The objectives of this study were to develop quadratic polynomial regression
      models using near-infrared spectroscopy that could determine the peel color
      difference, fruit firmness, soluble solids content (SSC), soluble sugar, organic
      acid components, and their relationships with the absorbance of chlorophyll
      (index of absorbance difference, IAD) in late maturing 'Xiahui 8' peach and
      'Xiaguang' nectarine fruits. The analysis was based on data for fruits at
      veraison, fruits at harvesting maturity, and all fruits. The results showed that
      firmness has the highest correlation coefficient with IAD. Prediction models for
      fruit maturity were established between firmness and the IAD of the two cultivars
      using the quadratic polynomial regression method. Further variance analysis on
      the one degree term and quadratic term of each equation showed that every partial
      regression coefficient reached a significant or extremely significant level. No
      significant difference was observed between estimated and observed values after
      regression prediction. The regression equations seem to fit well. Other peach and
      nectarine varieties were used to test the feasibility of maturity prediction by
      this method, and it was found that maturity was successfully predicted in all the
      samples. The result indicated that the IAD can be used as an index to predict
      peach fruit maturity.

PMID- 28505163
TI  - Anti-citrullinated peptide antibodies are the strongest predictor of clinically
      relevant radiographic progression in rheumatoid arthritis patients achieving
      remission or low disease activity: A post hoc analysis of a nationwide cohort in
      Japan.
AB  - OBJECTIVES: To determine prognostic factors of clinically relevant radiographic
      progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission
      or low disease activity (LDA) in clinical practice. METHODS: Using data from a
      nationwide, multicenter, prospective study in Japan, we evaluated 198 biological
      disease-modifying antirheumatic drug (bDMARD)-naive RA patients who were in
      remission or had LDA at study entry after being treated with conventional
      synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of
      modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic
      regression analysis to explore the factors to predict CRRP at 1 year. We used
      receiver operating characteristic (ROC) curve to estimate the performance of
      relevant variables for predicting CRRP. RESULTS: The mean Disease Activity Score
      in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 +/- 0.58 at
      study entry. During the 1-year observation, remission or LDA persisted in 72% of
      the patients. CRRP was observed in 7.6% of the patients. The multiple logistic
      regression analysis revealed that the independent variables to predict the
      development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity
      at baseline (OR = 15.2, 95%CI 2.64-299), time-integrated DAS28-ESR during the 1
      year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45), and the mTSS
      at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42). CONCLUSIONS: ACPA
      positivity was the strongest independent predictor of CRRP in patients with RA in
      remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor
      regarding the radiographic outcome of RA, even among patients showing a
      clinically favorable response to DMARDs.

PMID- 28505164
TI  - Human decellularized bone scaffolds from aged donors show improved osteoinductive
      capacity compared to young donor bone.
AB  - To improve the safe use of allograft bone, decellularization techniques may be
      utilized to produce acellular scaffolds. Such scaffolds should retain their
      innate biological and biomechanical capacity and support mesenchymal stem cell
      (MSC) osteogenic differentiation. However, as allograft bone is derived from a
      wide age-range, this study aimed to determine whether donor age impacts on the
      ability an osteoinductive, acellular scaffold produced from human bone to promote
      the osteogenic differentiation of bone marrow MSCs (BM-MSC). BM-MSCs from young
      and old donors were seeded on acellular bone cubes from young and old donors
      undergoing osteoarthritis related hip surgery. All combinations resulted in
      increased osteogenic gene expression, and alkaline phosphatase (ALP) enzyme
      activity, however BM-MSCs cultured on old donor bone displayed the largest
      increases. BM-MSCs cultured in old donor bone conditioned media also displayed
      higher osteogenic gene expression and ALP activity than those exposed to young
      donor bone conditioned media. ELISA and Luminex analysis of conditioned media
      demonstrated similar levels of bioactive factors between age groups; however, IGF
      binding protein 1 (IGFBP1) concentration was significantly higher in young donor
      samples. Additionally, structural analysis of old donor bone indicated an
      increased porosity compared to young donor bone. These results demonstrate the
      ability of a decellularized scaffold produced from young and old donors to
      support osteogenic differentiation of cells from young and old donors.
      Significantly, the older donor bone produced greater osteogenic differentiation
      which may be related to reduced IGFBP1 bioavailability and increased porosity,
      potentially explaining the excellent clinical results seen with the use of
      allograft from aged donors.

PMID- 28505166
TI  - Brain activation of semantic category-based grouping in multiple identity
      tracking task.
AB  - Using Multiple Identity Tracking task and the functional magnetic resonance
      imaging (fMRI) technology, the present study aimed to isolate and visualize the
      functional anatomy of neural systems involved in the semantic category-based
      grouping process. Three experiment conditions were selected and compared: the
      category-based targets grouping (TG) condition, the targets-distractors grouping
      (TDG) condition and the homogenous condition. In the TG condition, observers
      could utilize the categorical distinction between targets and distractors, to
      construct a uniform presentation of targets, that is, to form a group of the
      targets to facilitate tracking. In the TDG condition, half the targets and half
      the distractors belonged to the same category. Observers had to inhibit the
      grouping of targets and distractors in one category to complete tracking. In the
      homogenous condition, where targets and distractors consisted of the same
      objects, no grouping could be formed. The "TG-Homogenous" contrast (p<0.01)
      revealed the activation of the left fusiform and the pars triangularis of
      inferior frontal gyrus (IFG). The "TG-TDG" contrast only revealed the activation
      of the left anterior cingulate gyrus (ACC). The fusiform and IFG pars
      triangularis might participate in the representation of semantic knowledge, IFG
      pars triangularis might relate intensely with the classification of semantic
      categories. The ACC might be responsible for the initiation and maintenance of
      grouping representation.

PMID- 28505168
TI  - Development and validation of reversed-phase HPLC gradient method for the
      estimation of efavirenz in plasma.
AB  - Efavirenz is an anti-viral agent of non-nucleoside reverse transcriptase
      inhibitor category used as a part of highly active retroviral therapy for the
      treatment of infections of human immune deficiency virus type-1. A simple,
      sensitive and rapid reversed-phase high performance liquid chromatographic
      gradient method was developed and validated for the determination of efavirenz in
      plasma. The method was developed with high performance liquid chromatography
      using Waters X-Terra Shield, RP18 50 x 4.6 mm, 3.5 MUm column and a mobile phase
      consisting of phosphate buffer pH 3.5 and Acetonitrile. The elute was monitored
      with the UV-Visible detector at 260 nm with a flow rate of 1.5 mL/min. Tenofovir
      disoproxil fumarate was used as internal standard. The method was validated for
      linearity, precision, accuracy, specificity, robustness and data obtained were
      statistically analyzed. Calibration curve was found to be linear over the
      concentration range of 1-300 MUg/mL. The retention times of efavirenz and
      tenofovir disoproxil fumarate (internal standard) were 5.941 min and 4.356 min
      respectively. The regression coefficient value was found to be 0.999. The limit
      of detection and the limit of quantification obtained were 0.03 and 0.1 MUg/mL
      respectively. The developed HPLC method can be useful for quantitative
      pharmacokinetic parameters determination of efavirenz in plasma.

PMID- 28505167
TI  - Relationship of hyperlipidemia to comorbidities and lung function in COPD:
      Results of the COSYCONET cohort.
AB  - Although hyperlipidemia is common in COPD, its relationship to comorbidities,
      risk factors and lung function in COPD has not been studied in detail. Using the
      baseline data of the COSYCONET cohort we addressed this question. Data from 1746
      COPD patients (GOLD stage 1-4; mean age 64.6 y, mean FEV1%pred 57%) were
      evaluated, focusing on the comorbidities hyperlipidemia, diabetes and
      cardiovascular complex (CVC; including arterial hypertension, cardiac failure,
      ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears
      of smoking. The results of linear and logistic regression analyses were
      implemented into a path analysis model describing the multiple relationships
      between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower
      intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second
      (FEV1) when adjusting for its multiple relationships to risk factors and other
      comorbidities. These findings were robust in various statistical analyses. The
      associations between comorbidities and risk factors were in accordance with
      previous findings, thereby underlining the validity of our data. In conclusion,
      hyperlipidemia was associated with less hyperinflation and airway obstruction in
      patients with COPD. This surprising result might be due to different COPD
      phenotypes in these patients or related to effects of medication.

PMID- 28505169
TI  - Molecular basis of targeted therapy in T/NK-cell lymphoma/leukemia: A
      comprehensive genomic and immunohistochemical analysis of a panel of 33 cell
      lines.
AB  - T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable
      outcome, in which targeted treatments are still at a preliminary phase. To gain
      deeper insights into the deregulated mechanisms promoting this disease, we
      searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell
      lines for predictive markers of response to targeted therapy. To this end,
      targeted sequencing was performed alongside the expression of specific biomarkers
      corresponding to potentially activated survival pathways. The study identified
      TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found
      common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical
      analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p
      STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of
      T/NK-cell lymphoproliferative processes samples, with the partial exception of
      AITL cases. Integrated mutational and immunohistochemical analysis shows that
      mutational changes cannot fully explain the activation of key survival pathways
      and the resulting phenotypes. The combined integration of mutational/expression
      changes forms a useful tool with which new compounds may be assayed.

PMID- 28505170
TI  - IFN-gamma fails to overcome inhibition of selected macrophage activation events
      in response to pathogenic mycobacteria.
AB  - According to most models of mycobacterial infection, inhibition of the pro
      inflammatory macrophage immune responses contributes to the persistence of
      bacteria. Mycobacterium avium subsp. paratuberculosis (MAP) is a highly
      successful pathogen in cattle and sheep and is also implicated as the causative
      agent of Crohn's disease in humans. Pathogenic mycobacteria such as MAP have
      developed multiple strategies to evade host defence mechanisms including
      interfering with the macrophages' capacity to respond to IFN-gamma, a feature
      which might be lacking in non-pathogenic mycobacteria such as M. smegmatis. We
      hypothesized that pre-sensitisation of macrophages with the pro-inflammatory
      cytokine IFN-gamma would help in overcoming the inhibitory effect of MAP or its
      antigens on macrophage inflammatory responses. Herein we have compared a series
      of macrophage activation parameters in response to MAP and M. smegmatis as well
      as mycobacterial antigens. While IFN-gamma did overcome the inhibition in immune
      suppressive mechanisms in response to MAP antigen as well as M. smegmatis, we
      could not find a clear role for IFN-gamma in overcoming the inhibition of
      macrophage inflammatory responses to the pathogenic mycobacterium, MAP. We
      demonstrate that suppression of macrophage defence mechanisms by pathogenic
      mycobacteria is unlikely to be overcome by prior sensitization with IFN-gamma
      alone. This indicates that IFN-gamma signaling pathway-independent mechanisms may
      exist for overcoming inhibition of macrophage effector functions in response to
      pathogenic mycobacteria. These findings have important implications in
      understanding the survival mechanisms of pathogenic mycobacteria directed towards
      finding better therapeutics and vaccination strategies.

PMID- 28505171
TI  - Rapid deployment of a mobile biosafety level-3 laboratory in Sierra Leone during
      the 2014 Ebola virus epidemic.
AB  - BACKGROUND: Ebola virus emerged in West Africa in December 2013. The high
      population mobility and poor public health infrastructure in this region led to
      the development of the largest Ebola virus disease (EVD) outbreak to date.
      METHODOLOGY/PRINCIPAL FINDINGS: On September 26, 2014, China dispatched a Mobile
      Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to
      Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which
      allowed the diagnosis of suspected EVD cases in less than 4 hours from the time
      of sample receiving. This laboratory was composed of three container vehicles
      equipped with advanced ventilation system, communication system, electricity and
      gas supply system. We strictly applied multiple safety precautions to reduce
      exposure risks. Personnel, materials, water and air flow management were the key
      elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly
      collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols
      was detected. Potentially contaminated objects were also tested by collecting
      swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635
      suspected EVD cases (824 positive [50.4%]) were tested from September 28 to
      November 11, 2014, and no member of the diagnostic team was infected with Ebola
      virus or other pathogens, including Lassa fever. The specimens tested included
      blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%,
      respectively. The China mobile laboratory was thus instrumental in the EVD
      outbreak response by providing timely and reliable diagnostics.
      CONCLUSIONS/SIGNIFICANCE: The MBSL-3 Lab significantly contributed to
      establishing a suitable laboratory response capacity during the emergence of EVD
      in Sierra Leone.

PMID- 28505172
TI  - Increased nucleoside diphosphate kinase activity induces white spot syndrome
      virus infection in Litopenaeus vannamei.
AB  - Nucleoside diphosphate kinase (NDK), which has the same sequence as oncoprotein
      (OP) in humans, can induce nucleoside triphosphates in DNA replication by
      maintenance of the deoxynucleotide triphosphate (dNTP's) and is known to be
      regulated by viral infection in the shrimp Litopenaeus vannamei. This paper
      describes the relationship between NDK and white spot syndrome virus (WSSV)
      infection. The recombinant NDK was produced by a prokaryotic expression system.
      WSSV copy numbers and mRNA levels of IE1 and VP28 were significantly increased in
      shrimp injected with recombinant NDK at 72 h after WSSV infection. After
      synthesizing dsRNA-NDK and confirming the efficacy of NDK silencing, we recorded
      the cumulative mortality of WSSV-infected shrimp injected with NDK and dsRNA-NDK.
      A comparison between the results demonstrated that silencing NDK delayed the
      death of shrimps. These findings indicate that NDK has an important role
      influencing the replication of WSSV replication in shrimp. Furthermore, NDK may
      have potential target as a new therapeutic strategy against WSSV infection in
      shrimp.

PMID- 28505173
TI  - Continental divide: Predicting climate-mediated fragmentation and biodiversity
      loss in the boreal forest.
AB  - Climate change threatens natural landscapes through shifting distribution and
      abundance of species and attendant change in the structure and function of
      ecosystems. However, it remains unclear how climate-mediated variation in
      species' environmental niche space may lead to large-scale fragmentation of
      species distributions, altered meta-population dynamics and gene flow, and
      disrupted ecosystem integrity. Such change may be especially relevant when
      species distributions are restricted either spatially or to a narrow
      environmental niche, or when environments are rapidly changing. Here, we use
      range-wide environmental niche models to posit that climate-mediated range
      fragmentation aggravates the direct effects of climate change on species in the
      boreal forest of North America. We show that climate change will directly alter
      environmental niche suitability for boreal-obligate species of trees, birds and
      mammals (n = 12), with most species ranges becoming smaller and shifting
      northward through time. Importantly, species distributions will become
      increasingly fragmented, as characterized by smaller mean size and greater
      isolation of environmentally-suitable landscape patches. This loss is especially
      pronounced along the Ontario-Quebec border, where the boreal forest is narrowest
      and roughly 78% of suitable niche space could disappear by 2080. Despite the
      diversity of taxa surveyed, patterns of range fragmentation are remarkably
      consistent, with our models predicting that spruce grouse (Dendragapus
      canadensis), boreal chickadee (Poecile hudsonicus), moose (Alces americanus) and
      caribou (Rangifer tarandus) could have entirely disjunct east-west population
      segments in North America. These findings reveal potentially dire consequences of
      climate change on population continuity and species diversity in the boreal
      forest, highlighting the need to better understand: 1) extent and primary drivers
      of anticipated climate-mediated range loss and fragmentation; 2) diversity of
      species to be affected by such change; 3) potential for rapid adaptation in the
      most strongly-affected areas; and 4) potential for invasion by replacement
      species.

PMID- 28505175
TI  - Structural insights into reptarenavirus cap-snatching machinery.
AB  - Cap-snatching was first discovered in influenza virus. Structures of the involved
      domains of the influenza virus polymerase, namely the endonuclease in the PA
      subunit and the cap-binding domain in the PB2 subunit, have been solved. Cap
      snatching endonucleases have also been demonstrated at the very N-terminus of the
      L proteins of mammarena-, orthobunya-, and hantaviruses. However, a cap-binding
      domain has not been identified in an arena- or bunyavirus L protein so far. We
      solved the structure of the 326 C-terminal residues of the L protein of
      California Academy of Sciences virus (CASV), a reptarenavirus, by X-ray
      crystallography. The individual domains of this 37-kDa fragment (L-Cterm) as well
      as the domain arrangement are structurally similar to the cap-binding and
      adjacent domains of influenza virus polymerase PB2 subunit, despite the absence
      of sequence homology, suggesting a common evolutionary origin. This enabled
      identification of a region in CASV L-Cterm with similarity to a cap-binding site;
      however, the typical sandwich of two aromatic residues was missing. Consistent
      with this, cap-binding to CASV L-Cterm could not be detected biochemically. In
      addition, we solved the crystal structure of the corresponding endonuclease in
      the N-terminus of CASV L protein. It shows a typical endonuclease fold with an
      active site configuration that is essentially identical to that of known
      mammarenavirus endonuclease structures. In conclusion, we provide evidence for a
      presumably functional cap-snatching endonuclease in the N-terminus and a
      degenerate cap-binding domain in the C-terminus of a reptarenavirus L protein.
      Implications of these findings for the cap-snatching mechanism in arenaviruses
      are discussed.

PMID- 28505174
TI  - Extracellular matrix nitration alters growth factor release and activates
      bioactive complement in human retinal pigment epithelial cells.
AB  - PURPOSE: We have shown previously that non-enzymatic nitration (NEN) of the
      extracellular matrix (ECM), which serves as a model of Bruch's membrane (BM)
      aging, has a profound effect on the behavior of the overlying retinal pigment
      epithelial (RPE) cells, including altered phagocytic ability, reduced cell
      adhesion, and inhibition of proliferation. We know that transplanted RPE
      monolayers will encounter a hostile sub-RPE environment, including age-related
      alterations in BM that may compromise cell function and survival. Here we use our
      previous NEN model of BM aging to determine the effects of NEN of the ECM on
      growth factor release and complement activation in RPE cells. METHODS: Human
      induced-pluripotent stem cells (iPSCs) were differentiated into RPE cells, and
      confirmed by immunohistochemistry, confocal microscopy, and polymerase chain
      reaction. IPSC-derived RPE cells were plated onto RPE-derived ECM under untreated
      or nitrite-modified conditions. Cells were cultured for 7 days and barrier
      function measured by transepithelial resistance (TER). Vascular endothelial
      growth factor (VEGF), pigment epithelium-derived factor (PEDF), and complement
      component C3a were measured using enzyme-linked immunosorbent assay (ELISA).
      RESULTS: On average nitrite-modified ECM increased VEGF release both apically and
      basally by 0.15 +/- 0.014 ng/mL (p <0.0001) and 0.21 +/- 0.022 ng/mL (p <0.0001),
      respectively, in iPSC-derived RPE cells. Nitrite-modified ECM increased PEDF
      release in iPSC-derived RPE cells apically by 0.16 +/- 0.031 ng/mL (p <0.0001),
      but not basally (0.27 +/- 0.015 vs. 0.32 +/- 0.029 ng/mL, (p >0.05)). Nitrite
      modified ECM increased production of C3a in iPSC-derived RPE cells by 0.52 +/-
      0.123 ng/mL (p <0.05). CONCLUSION: Nitrite-modified ECM increased VEGF, PEDF
      release, and C3a production in human iPSC-derived RPE cells. This model
      demonstrates changes seen in the basement membrane can lead to alterations in the
      cell biology of the RPE cells that may be related to the development of age
      related macular degeneration.

PMID- 28505176
TI  - Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular
      infection offers insight into coordinated virulence.
AB  - A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), the
      causative agent of tuberculosis, is the capacity to survive within host
      macrophages. Although several factors required for this survival have been
      identified, a comprehensive knowledge of such factors and how they work together
      to manipulate the host environment to benefit bacterial survival are not well
      understood. To systematically identify Mtb factors required for intracellular
      growth, we screened an arrayed, non-redundant Mtb transposon mutant library by
      high-content imaging to characterize the mutant-macrophage interaction. Based on
      a combination of imaging features, we identified mutants impaired for
      intracellular survival. We then characterized the phenotype of infection with
      each mutant by profiling the induced macrophage cytokine response. Taking a
      systems-level approach to understanding the biology of identified mutants, we
      performed a multiparametric analysis combining pathogen and host phenotypes to
      predict functional relationships between mutants based on clustering. Strikingly,
      mutants defective in two well-known virulence factors, the ESX-1 protein
      secretion system and the virulence lipid phthiocerol dimycocerosate (PDIM),
      clustered together. Building upon the shared phenotype of loss of the macrophage
      type I interferon (IFN) response to infection, we found that PDIM production and
      export are required for coordinated secretion of ESX-1-substrates, for phagosomal
      permeabilization, and for downstream induction of the type I IFN response.
      Multiparametric clustering also identified two novel genes that are required for
      PDIM production and induction of the type I IFN response. Thus, multiparametric
      analysis combining host and pathogen infection phenotypes can be used to identify
      novel functional relationships between genes that play a role in infection.

PMID- 28505178
TI  - A reverse dot blot assay for the screening of twenty mutations in four genes
      associated with NSHL in a Chinese population.
AB  - BACKGROUND: Congenital deafness is one of the most distressing disorders
      affecting humanity and exhibits a high incidence worldwide. Most cases of
      congenital deafness in the Chinese population are caused by defects in a limited
      number of genes. A convenient and reliable method for detecting common deafness
      related gene mutations in the Chinese population is required. METHODS: We
      developed a PCR-reverse dot blot (RDB) assay for screening 20 hotspot mutations
      of GJB2, GJB3, SLC26A4, and MT-RNR1, which are common non-syndromic hearing loss
      (NSHL)-associated genes in the Chinese population. The PCR-RDB assay consists of
      multiplex PCR amplifications of 10 fragments in the target sequence of the four
      above-mentioned genes in wild-type and mutant genomic DNA samples followed by
      hybridization to a test strip containing allele-specific oligonucleotide probes.
      We applied our method to a set of 225 neonates with deafness gene mutations and
      30 normal neonates. RESULTS: The test was validated through direct sequencing in
      a blinded study with 100% concordance. CONCLUSIONS: The results demonstrated that
      our reverse dot blot assay is a reliable and effective genetic screening method
      for identifying carriers and individuals with NSHL among the Chinese population.

PMID- 28505177
TI  - The clinico-radiological paradox of cognitive function and MRI burden of white
      matter lesions in people with multiple sclerosis: A systematic review and meta
      analysis.
AB  - BACKGROUND: Moderate correlation exists between the imaging quantification of
      brain white matter lesions and cognitive performance in people with multiple
      sclerosis (MS). This may reflect the greater importance of other features,
      including subvisible pathology, or methodological limitations of the primary
      literature. OBJECTIVES: To summarise the cognitive clinico-radiological paradox
      and explore the potential methodological factors that could influence the
      assessment of this relationship. METHODS: Systematic review and meta-analysis of
      primary research relating cognitive function to white matter lesion burden.
      RESULTS: Fifty papers met eligibility criteria for review, and meta-analysis of
      overall results was possible in thirty-two (2050 participants). Aggregate
      correlation between cognition and T2 lesion burden was r = -0.30 (95% confidence
      interval: -0.34, -0.26). Wide methodological variability was seen, particularly
      related to key factors in the cognitive data capture and image analysis
      techniques. CONCLUSIONS: Resolving the persistent clinico-radiological paradox
      will likely require simultaneous evaluation of multiple components of the complex
      pathology using optimum measurement techniques for both cognitive and MRI feature
      quantification. We recommend a consensus initiative to support common standards
      for image analysis in MS, enabling benchmarking while also supporting ongoing
      innovation.

PMID- 28505179
TI  - Food restriction increase the expression of mTORC1 complex genes in the skeletal
      muscle of juvenile pacu (Piaractus mesopotamicus).
AB  - Skeletal muscle is capable of phenotypic adaptation to environmental factors,
      such as nutrient availability, by altering the balance between muscle catabolism
      and anabolism that in turn coordinates muscle growth. Small noncoding RNAs, known
      as microRNAs (miRNAs), repress the expression of target mRNAs, and many studies
      have demonstrated that miRNAs regulate the mRNAs of catabolic and anabolic genes.
      We evaluated muscle morphology, gene expression of components involved in
      catabolism, anabolism and energetic metabolism and miRNAs expression in both the
      fast and slow muscle of juvenile pacu (Piaractus mesopotamicus) during food
      restriction and refeeding. Our analysis revealed that short periods of food
      restriction followed by refeeding predominantly affected fast muscle, with
      changes in muscle fiber diameter and miRNAs expression. There was an increase in
      the mRNA levels of catabolic pathways components (FBXO25, ATG12, BCL2) and
      energetic metabolism-related genes (PGC1alpha and SDHA), together with a decrease
      in PPARbeta/delta mRNA levels. Interestingly, an increase in mRNA levels of
      anabolic genes (PI3K and mTORC1 complex: mTOR, mLST8 and RAPTOR) was also
      observed during food restriction. After refeeding, muscle morphology showed
      similar patterns of the control group; the majority of genes were slightly up- or
      down-regulated in fast and slow muscle, respectively; the levels of all miRNAs
      increased in fast muscle and some of them decreased in slow muscle. Our findings
      demonstrated that a short period of food restriction in juvenile pacu had a
      considerable impact on fast muscle, increasing the expression of anabolic (PI3K
      and mTORC1 complex: mTOR, mLST8 and RAPTOR) and energetic metabolism genes. The
      miRNAs (miR-1, miR-206, miR-199 and miR-23a) were more expressed during refeeding
      and while their target genes (IGF-1, mTOR, PGC1alpha and MAFbx), presented a
      decreased expression. The alterations in mTORC1 complex observed during fasting
      may have influenced the rates of protein synthesis by using amino acids from
      protein degradation as an alternative mechanism to preserve muscle phenotype and
      metabolic demand maintenance.

PMID- 28505180
TI  - Empathic nonverbal behavior increases ratings of both warmth and competence in a
      medical context.
AB  - In medicine, it is critical that clinicians demonstrate both empathy (perceived
      as warmth) and competence. Perceptions of these qualities are often intuitive and
      are based on nonverbal behavior. Emphasizing both warmth and competence may prove
      problematic, however, because there is evidence that they are inversely related
      in other settings. We hypothesize that perceptions of physician competence will
      instead be positively correlated with perceptions of physician warmth and
      empathy, potentially due to changing conceptions of the physician's role. We test
      this hypothesis in an analog medical context using a large online sample,
      manipulating physician nonverbal behaviors suggested to communicate empathy (e.g.
      eye contact) and competence (the physician's white coat). Participants rated
      physicians displaying empathic nonverbal behavior as more empathic, warm, and
      more competent than physicians displaying unempathic nonverbal behavior,
      adjusting for mood. We found no warmth/competence tradeoff and, additionally, no
      significant effects of the white coat. Further, compared with male participants,
      female participants perceived physicians displaying unempathic nonverbal behavior
      as less empathic. Given the significant consequences of clinician empathy, it is
      important for clinicians to learn how nonverbal behavior contributes to
      perceptions of warmth, and use it as another tool to improve their patients'
      emotional and physical health.

PMID- 28505181
TI  - Overexpression of pyruvate dehydrogenase kinase 1 in retinoblastoma: A potential
      therapeutic opportunity for targeting vitreous seeds and hypoxic regions.
AB  - Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic
      reprogramming of tumors, is induced in several tumors including glioblastoma,
      breast cancer and melanoma. However, the role played by PDK1 is not studied in
      retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in
      RB clinical samples, and studied its inhibition as a strategy to decrease cell
      growth and migration. We show that PDK1 is specifically overexpressed in RB
      patient samples especially in vitreous seeds and hypoxic regions and cell lines
      compared to control retina using immunohistochemistry and real-time PCR. Our
      results further demonstrate that inhibition of PDK1 using small molecule
      inhibitors dichloroacetic acid (DCA) and dichloroacetophenone (DAP) resulted in
      reduced cell growth and increased apoptosis. We also confirm that combination
      treatment of DCA with chemotherapeutic agent carboplatin further enhanced the
      therapeutic efficacy compared to single drug treatment. In addition, we observed
      changes in glucose uptake, lactate and reactive oxygen species (ROS) levels as
      well as decreased cell migration in response to PDK1 inhibition. Additionally, we
      show that DCA treatment led to inhibition of PI3K/Akt pathway and reduction in
      PDK1 protein levels. Overall, our data suggest that targeting PDK1 could be a
      novel therapeutic strategy for RB.

PMID- 28505182
TI  - Using NextRAD sequencing to infer movement of herbivores among host plants.
AB  - Herbivores often move among spatially interspersed host plants, tracking high
      quality resources through space and time. This dispersal is of particular
      interest for vectors of plant pathogens. Existing molecular tools to track such
      movement have yielded important insights, but often provide insufficient genetic
      resolution to infer spread at finer spatiotemporal scales. Here, we explore the
      use of Nextera-tagmented reductively-amplified DNA (NextRAD) sequencing to infer
      movement of a highly-mobile winged insect, the potato psyllid (Bactericera
      cockerelli), among host plants. The psyllid vectors the pathogen that causes
      zebra chip disease in potato (Solanum tuberosum), but understanding and managing
      the spread of this pathogen is limited by uncertainty about the insect's host
      plant(s) outside of the growing season. We identified 1,978 polymorphic loci
      among psyllids separated spatiotemporally on potato or in patches of bittersweet
      nightshade (S. dulcumara), a weedy plant proposed to be the source of potato
      colonizing psyllids. A subset of the psyllids on potato exhibited genetic
      similarity to insects on nightshade, consistent with regular movement between
      these two host plants. However, a second subset of potato-collected psyllids was
      genetically distinct from those collected on bittersweet nightshade; this
      suggests that a currently unrecognized source, i.e., other nightshade patches or
      a third host-plant species, could be contributing to psyllid populations in
      potato. Oftentimes, dispersal of vectors of pathogens must be tracked at a fine
      scale in order to understand, predict, and manage disease spread. We demonstrate
      that emerging sequencing technologies that detect genome-wide SNPs of a vector
      can be used to infer such localized movement.

PMID- 28505183
TI  - High-order epistasis shapes evolutionary trajectories.
AB  - High-order epistasis-where the effect of a mutation is determined by interactions
      with two or more other mutations-makes small, but detectable, contributions to
      genotype-fitness maps. While epistasis between pairs of mutations is known to be
      an important determinant of evolutionary trajectories, the evolutionary
      consequences of high-order epistasis remain poorly understood. To determine the
      effect of high-order epistasis on evolutionary trajectories, we computationally
      removed high-order epistasis from experimental genotype-fitness maps containing
      all binary combinations of five mutations. We then compared trajectories through
      maps both with and without high-order epistasis. We found that high-order
      epistasis strongly shapes the accessibility and probability of evolutionary
      trajectories. A closer analysis revealed that the magnitude of epistasis, not its
      order, predicts is effects on evolutionary trajectories. We further find that
      high-order epistasis makes it impossible to predict evolutionary trajectories
      from the individual and paired effects of mutations. We therefore conclude that
      high-order epistasis profoundly shapes evolutionary trajectories through genotype
      fitness maps.

PMID- 28505184
TI  - SteadyCom: Predicting microbial abundances while ensuring community stability.
AB  - Genome-scale metabolic modeling has become widespread for analyzing microbial
      metabolism. Extending this established paradigm to more complex microbial
      communities is emerging as a promising way to unravel the interactions and
      biochemical repertoire of these omnipresent systems. While several modeling
      techniques have been developed for microbial communities, little emphasis has
      been placed on the need to impose a time-averaged constant growth rate across all
      members for a community to ensure co-existence and stability. In the absence of
      this constraint, the faster growing organism will ultimately displace all other
      microbes in the community. This is particularly important for predicting steady
      state microbiota composition as it imposes significant restrictions on the
      allowable community membership, composition and phenotypes. In this study, we
      introduce the SteadyCom optimization framework for predicting metabolic flux
      distributions consistent with the steady-state requirement. SteadyCom can be
      rapidly converged by iteratively solving linear programming (LP) problem and the
      number of iterations is independent of the number of organisms. A significant
      advantage of SteadyCom is compatibility with flux variability analysis. SteadyCom
      is first demonstrated for a community of four E. coli double auxotrophic mutants
      and is then applied to a gut microbiota model consisting of nine species, with
      representatives from the phyla Bacteroidetes, Firmicutes, Actinobacteria and
      Proteobacteria. In contrast to the direct use of FBA, SteadyCom is able to
      predict the change in species abundance in response to changes in diets with
      minimal additional imposed constraints on the model. By randomizing the uptake
      rates of microbes, an abundance profile with a good agreement to experimental gut
      microbiota is inferred. SteadyCom provides an important step towards the cross
      cutting task of predicting the composition of a microbial community in a given
      environment.

PMID- 28505187
TI  - Recurrence of Dupuytren's contracture: A consensus-based definition.
AB  - PURPOSE: One of the major determinants of Dupyutren disease (DD) treatment
      efficacy is recurrence of the contracture. Unfortunately, lack of agreement in
      the literature on what constitutes recurrence makes it nearly impossible to
      compare the multiple treatments alternatives available today. The aim of this
      study is to bring an unbiased pool of experts to agree upon what would be
      considered a recurrence of DD after treatment; and from that consensus establish
      a much-needed definition for DD recurrence. METHODS: To reach an expert consensus
      on the definition of recurrence we used the Delphi method and invited 43
      Dupuytren's research and treatment experts from 10 countries to participate by
      answering a series of questionnaire rounds. After each round the answers were
      analyzed and the experts received a feedback report with another questionnaire
      round to further hone in of the definition. We defined consensus when at least
      70% of the experts agreed on a topic. RESULTS: Twenty-one experts agreed to
      participate in this study. After four consensus rounds, we agreed that DD
      recurrence should be defined as "more than 20 degrees of contracture recurrence
      in any treated joint at one year post-treatment compared to six weeks post
      treatment". In addition, "recurrence should be reported individually for every
      treated joint" and afterwards measurements should be repeated and reported
      yearly. CONCLUSION: This study provides the most comprehensive to date definition
      of what should be considered recurrence of DD. These standardized criteria should
      allow us to better evaluate the many treatment alternatives.

PMID- 28505185
TI  - Combined treatment of miltefosine and paromomycin delays the onset of
      experimental drug resistance in Leishmania infantum.
AB  - BACKGROUND: Since miltefosine monotherapy against visceral leishmaniasis (VL)
      caused by Leishmania donovani has been discontinued in the Indian subcontinent
      due to an increase in the number of treatment failures, single dose liposomal
      amphotericin B is now advocated as a treatment option of choice. Paromomycin
      miltefosine combination therapy can be used as substitute first-line treatment in
      regions without cold-chain potential. Previous laboratory studies in the closely
      related species Leishmania infantum have demonstrated that paromomycin
      monotherapy fairly rapidly selects for resistance producing a phenotype with
      increased fitness. Given the possible clinical implications of these findings for
      the current field situation, the present study aimed to identify the potential
      hazards of paromomycin-miltefosine combination therapy. PRINCIPAL FINDINGS: Drug
      interaction studies using the fixed-ratio isobologram method revealed an
      indifferent interaction between paromomycin and miltefosine. In hamsters infected
      with L. infantum, the combination resulted in cumulative efficacy in reducing
      parasite burdens in the liver, spleen and bone marrow. Selected resistant lines
      against the single drugs did not display cross-resistance. When the intracellular
      amastigote stage was repeatedly exposed to the paromomycin-miltefosine
      combination, either in vitro or in vivo, no significant susceptibility decrease
      towards either drug was noted. CONCLUSIONS: These results suggest that
      implementation of paromomycin-miltefosine combination therapy indeed could
      represent a safe and affordable treatment option for L. donovani VL as
      miltefosine appears to overrule the anticipated rapid development of PMM
      resistance.

PMID- 28505186
TI  - In Situ complement activation and T-cell immunity in leprosy spectrum: An
      immunohistological study on leprosy lesional skin.
AB  - Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition
      worsens often during and long after treatment. Clearance of bacterial antigens
      including lipoarabinomannan (LAM) during and after treatment in leprosy patients
      is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves
      by in situ generation of the membrane attack complex (MAC). Investigating the
      role of complement activation in skin lesions of leprosy patients might provide
      insight into the dynamics of in situ immune reactivity and the destructive
      pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy
      patients, whether M. leprae antigen LAM deposition correlates with the deposition
      of complement activation products MAC and C3d on nerves and cells in the
      surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary
      leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n =
      6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The
      percentage of C3d, MAC and LAM deposition was significantly higher in the skin
      biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p =
      <0.001 and p = <0.001 respectively), with a significant association between LAM
      and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001
      and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary
      patients, MAC deposition was found on axons and co-localizing with LAM. In skin
      lesions of paucibacillary patients, we found C3d positive T-cells in and
      surrounding granulomas, but hardly any MAC deposition. In addition, MAC
      immunoreactivity was increased in both ENL and RR skin lesions compared to non
      reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present
      findings demonstrate that complement is deposited in skin lesions of leprosy
      patients, suggesting that inflammation driven by complement activation might
      contribute to nerve damage in the lesions of these patients. This should be
      regarded as an important factor in M. leprae nerve damage pathology.

PMID- 28505188
TI  - Early childhood lung function is a stronger predictor of adolescent lung function
      in cystic fibrosis than early Pseudomonas aeruginosa infection.
AB  - OBJECTIVE: Pseudomonas aeruginosa has been suggested as a major determinant of
      poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a
      role. Our objective was to investigate the association of early childhood
      Pseudomonas infection on differences in lung function in adolescence with CF.
      METHODS: Two populations of subjects with CF were studied: from the Gene Modifier
      Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung
      disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed
      with CF by newborn screening. Associations of Pseudomonas infection and lung
      function in early childhood with lung function in adolescence were investigated
      using multivariate linear regression analyses. RESULTS: Among GMS subjects, those
      with severe adolescent lung disease had worse lung function in childhood (FEV1 25
      percentage points lower) compared to subjects with mild adolescent lung disease,
      regardless of early childhood Pseudomonas status. Among NBS subjects, those with
      lowest adolescent lung function had significantly lower early childhood lung
      function and faster rate of decline in FEV1 than subjects with highest adolescent
      lung function; early Pseudomonas infection was not associated with rate of FEV1
      decline. The strongest predictor of adolescent lung function was early childhood
      lung function. Subjects with a higher percentage of cultures positive for
      Pseudomonas before age 6 or a lower BMI at 2-4 years old also had lower
      adolescent lung function, though these associations were not as strong as with
      early childhood lung function. CONCLUSIONS: In separate analyses of two distinct
      populations of subjects with CF, we found a strong correlation between lower lung
      function in early childhood and adolescence, regardless of early childhood
      Pseudomonas status. Factors in addition to early Pseudomonas infection have a
      strong impact on lung function in early childhood in CF. Further exploration may
      identify novel underlying genetic or environmental factors that predispose
      children with CF to early loss of lung function.

PMID- 28505189
TI  - Small and big Hodgkin-Reed-Sternberg cells of Hodgkin lymphoma cell lines L-428
      and L-1236 lack consistent differences in gene expression profiles and are
      capable to reconstitute each other.
AB  - The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly
      multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been
      shown that giant HRS cells evolve from small Hodgkin cells by incomplete
      cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this
      phenomenon particularly takes place in this lymphoma and what the differences
      between these cell types of variable sizes are. The aim of the present study was
      to characterize microdissected small and giant HRS cells by gene expression
      profiling and to assess differences of clonal growth behavior as well as
      susceptibility toward cytotoxic intervention between these different cell types
      to provide more insight into their distinct cellular potential. Applying
      stringent filter criteria, only two differentially expressed genes between small
      and giant HRS cells, SHFM1 and LDHB, were identified. With looser filter
      criteria, 13 genes were identified to be differentially overexpressed in small
      compared to giant HRS cells. These were mainly related to energy metabolism and
      protein synthesis, further suggesting that small Hodgkin cells resemble the
      proliferative compartment of cHL. SHFM1, which is known to be involved in the
      generation of giant cells, was downregulated in giant RS cells at the RNA level.
      However, reduced mRNA levels of SHFM1, LDHB and HSPA8 did not translate into
      decreased protein levels in giant HRS cells. In cell culture experiments it was
      observed that the fraction of small and big HRS cells was adjusted to the basic
      level several days after enrichment of these populations via cell sorting,
      indicating that small and big HRS cells can reconstitute the full spectrum of
      cells usually observed in the culture. However, assessment of clonal growth of
      HRS cells indicated a significantly reduced potential of big HRS cells to form
      single cell colonies. Taken together, our findings pinpoint to strong
      similarities but also some differences between small and big HRS cells.

PMID- 28505190
TI  - Dynamic interaction between fetal adversity and a genetic score reflecting
      dopamine function on developmental outcomes at 36 months.
AB  - BACKGROUND: Fetal adversity, evidenced by poor fetal growth for instance, is
      associated with increased risk for several diseases later in life. Classical cut
      offs to characterize small (SGA) and large for gestational age (LGA) newborns are
      used to define long term vulnerability. We aimed at exploring the possible
      dynamism of different birth weight cut-offs in defining vulnerability in
      developmental outcomes (through the Bayley Scales of Infant and Toddler
      Development), using the example of a gene vs. fetal adversity interaction
      considering gene choices based on functional relevance to the studied outcome.
      METHODS: 36-month-old children from an established prospective birth cohort
      (Maternal Adversity, Vulnerability, and Neurodevelopment) were classified
      according to birth weight ratio (BWR) (SGA <=0.85, LGA >1.15, exploring a wide
      range of other cut-offs) and genotyped for polymorphisms associated with dopamine
      signaling (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10- repeat,
      Met/Met-COMT), composing a score based on the described function, in which
      hypofunctional variants received lower scores. RESULTS: There were 251 children
      (123 girls and 128 boys). Using the classic cut-offs (0.85 and 1.15), there were
      no statistically significant interactions between the neonatal groups and the
      dopamine genetic score. However, when changing the cut-offs, it is possible to
      see ranges of BWR that could be associated with vulnerability to poorer
      development according to the variation in the dopamine function. CONCLUSION: The
      classic birth weight cut-offs to define SGA and LGA newborns should be seen with
      caution, as depending on the outcome in question, the protocols for long-term
      follow up could be either too inclusive-therefore most costly, or unable to
      screen true vulnerabilities-and therefore ineffective to establish early
      interventions and primary prevention.

PMID- 28505192
TI  - Large herbivores in novel ecosystems - Habitat selection by red deer (Cervus
      elaphus) in a former brown-coal mining area.
AB  - After centuries of range contraction, many megafauna species are recolonizing
      parts of Europe. One example is the red deer (Cervus elaphus), which was able to
      expand its range and is now found in half the areas it inhabited in the beginning
      of the 19th century. Herbivores are important ecosystem engineers, influencing
      e.g. vegetation. Knowledge on their habitat selection and their influence on
      ecosystems might be crucial for future landscape management, especially for
      hybrid and novel ecosystems emerging in post-industrial landscapes. In this
      study, red deer habitat selection was studied in a former brown-coal mining area
      in Denmark. Here, natural settings were severely changed during the mining
      activity and its current landscape is in large parts managed by hunters as
      suitable deer habitat. We assessed red deer habitat preferences through feces
      presence and camera traps combined with land cover data from vegetation sampling,
      remote sensing and official geographic data. Red deer occurrence was negatively
      associated with human disturbance and positively associated with forage
      availability, tree cover and mean terrain height. Apparently, red deer are
      capable of recolonizing former industrial landscapes quite well if key conditions
      such as forage abundance and cover are appropriate. In the absence of carnivores,
      human disturbance, such as a hunting regime is a main reason why deer avoid
      certain areas. The resulting spatial heterogeneity red deer showed in their
      habitat use of the study area might be a tool to preserve mosaic landscapes of
      forest and open habitats and thus promote biodiversity in abandoned post
      industrial landscapes.

PMID- 28505191
TI  - Lp25 membrane protein from pathogenic Leptospira spp. is associated with
      rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of
      leptospirosis.
AB  - Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo-
      or normokalemia. Higher serum potassium levels are observed in non-survivor
      patients and may have been caused by more severe AKI, metabolic disarrangement,
      or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level
      and maximum serum creatinine level has been observed in these patients, which
      suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32
      and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but
      these proteins have no known function. This study evaluated the effect of these
      proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that
      appears responsible for the development of oliguric AKI associated with
      hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum
      phosphate). This study is the first characterization of a leptospiral outer
      membrane protein that is associated with severe manifestations of leptospirosis.
      Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced
      AKI could protect animals and patients from severe forms of this disease and
      decrease mortality.

PMID- 28505193
TI  - The Drosophila orthologue of the INT6 onco-protein regulates mitotic microtubule
      growth and kinetochore structure.
AB  - INT6/eIF3e is a highly conserved component of the translation initiation complex
      that interacts with both the 26S proteasome and the COP9 signalosome, two
      complexes implicated in ubiquitin-mediated protein degradation. The INT6 gene was
      originally identified as the insertion site of the mouse mammary tumor virus
      (MMTV), and later shown to be involved in human tumorigenesis. Here we show that
      depletion of the Drosophila orthologue of INT6 (Int6) results in short mitotic
      spindles and deformed centromeres and kinetochores with low intra-kinetochore
      distance. Poleward flux of microtubule subunits during metaphase is reduced,
      although fluorescence recovery after photobleaching (FRAP) demonstrates that
      microtubules remain dynamic both near the kinetochores and at spindle poles.
      Mitotic progression is delayed during metaphase due to the activity of the
      spindle assembly checkpoint (SAC). Interestingly, a deubiquitinated form of the
      kinesin Klp67A (a putative orthologue of human Kif18A) accumulates near the
      kinetochores in Int6-depleted cells. Consistent with this finding, Klp67A
      overexpression mimics the Int6 RNAi phenotype. Furthermore, simultaneous
      depletion of Int6 and Klp67A results in a phenotype identical to RNAi of just
      Klp67A, which indicates that Klp67A deficiency is epistatic over Int6 deficiency.
      We propose that Int6-mediated ubiquitination is required to control the activity
      of Klp67A. In the absence of this control, excess of Klp67A at the kinetochore
      suppresses microtubule plus-end polymerization, which in turn results in reduced
      microtubule flux, spindle shortening, and centromere/kinetochore deformation.

PMID- 28505194
TI  - Comparative effectiveness of angiotensin-converting enzyme inhibitors versus
      angiotensin II receptor blockers for major renal outcomes in patients with
      diabetes: A 15-year cohort study.
AB  - BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II
      receptor blockers (ARBs) are considered to have similar renoprotective effects;
      so far there has been no consensus about their priorities. This study aimed to
      compare ACEIs and ARBs for major renal outcomes and survival in a 15-year cohort
      of adults with diabetes. METHODS: This study utilized Taiwan's medical and
      pharmacy claims data in the Longitudinal Cohort of Diabetes Patients. The primary
      outcome was long-term dialysis, and secondary outcomes were hospitalization for
      acute kidney injury, hospitalization for hyperkalemia, all-cause death,
      cardiovascular death, and non-cardiovascular death. Cox proportional hazards
      models were used to estimate the hazard ratios (HRs) and 95% confidence intervals
      (CIs) for outcomes comparing ACEIs with ARBs. We conducted subgroup analyses and
      interaction tests among patients with different age and comorbid diseases.
      RESULTS: A total of 34,043 patients received ACEIs and 23,772 patients received
      ARBs. No differences were found for primary or secondary outcomes in the main
      analyses. ACEIs showed significantly lower hazard than ARBs for long-term
      dialysis among patients with cardiovascular disease (HR 0.80, 95% CI 0.66-0.97,
      interaction P = 0.003) or chronic kidney disease (0.81, 0.71-0.93, interaction P
      = 0.001). CONCLUSIONS: Our analyses show similar effects of ACEIs and ARBs in
      patients with diabetes. However, ACEIs might provide additional renoprotective
      effects among patients who have cardiovascular disease or chronic kidney disease.

PMID- 28505195
TI  - Dose escalation study to evaluate safety, tolerability and efficacy of
      intravenous etoposide phosphate administration in 27 dogs with multicentric
      lymphoma.
AB  - Comparative oncology has shown that naturally occurring canine cancers are of
      valuable and translatable interest for the understanding of human cancer biology
      and the characterization of new therapies. This work was part of a comparative
      oncology project assessing a new, clinical-stage topoisomerase II inhibitor and
      comparing it with etoposide in dogs with spontaneous lymphoma with the objective
      to translate findings from dogs to humans. Etoposide is a topoisomerase II
      inhibitor widely used in various humans' solid and hematopoietic cancer, but
      little data is available concerning its potential antitumor efficacy in dogs.
      Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to
      be better tolerated in dogs. The objectives of this study were to assess the
      safety, the tolerability and the efficacy of intravenous etoposide phosphate in
      dogs with multicentric lymphoma. Seven dose levels were evaluated in a
      traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade
      multicentric lymphoma were enrolled and treated with three cycles of etoposide
      phosphate IV injections every 2 weeks. Adverse effects were graded according to
      the Veterinary Cooperative Oncology Group criteria. A complete end-staging was
      realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At
      this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only
      a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no
      hypersensitivity reaction were reported at this dose level. Beyond the
      characterization of etoposide clinical efficacy in dogs, this study underlined
      the clinical and therapeutic homologies between dog and human lymphomas.

PMID- 28505196
TI  - Unveiling a novel transient druggable pocket in BACE-1 through molecular
      simulations: Conformational analysis and binding mode of multisite inhibitors.
AB  - The critical role of BACE-1 in the formation of neurotoxic beta-amyloid peptides
      in the brain makes it an attractive target for an efficacious treatment of
      Alzheimer's disease. However, the development of clinically useful BACE-1
      inhibitors has proven to be extremely challenging. In this study we examine the
      binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed
      by synergistic combination of two fragments-huprine and rhein-that individually
      are endowed with very low activity against BACE-1. Examination of crystal
      structures reveals no appropriate binding site large enough to accommodate 1.
      Therefore we have examined the conformational flexibility of BACE-1 through
      extended molecular dynamics simulations, paying attention to the highly flexible
      region shaped by loops 8-14, 154-169 and 307-318. The analysis of the protein
      dynamics, together with studies of pocket druggability, has allowed us to detect
      the transient formation of a secondary binding site, which contains Arg307 as a
      key residue for the interaction with small molecules, at the edge of the
      catalytic cleft. The formation of this druggable "floppy" pocket would enable the
      binding of multisite inhibitors targeting both catalytic and secondary sites.
      Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds
      support the feasibility of this hypothesis. The results provide a basis to
      explain the high inhibitory potency of the two enantiomeric forms of 1, together
      with the large dependence on the length of the oligomethylenic linker.
      Furthermore, the multisite hypothesis has allowed us to rationalize the
      inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically
      regarding the apparent lack of sensitivity of the inhibition constant to the
      chemical modifications introduced in the chromene unit. Overall, these findings
      pave the way for the exploration of novel functionalities in the design of
      optimized BACE-1 multisite inhibitors.

PMID- 28505197
TI  - Structure of Ca2+-binding protein-6 from Entamoeba histolytica and its
      involvement in trophozoite proliferation regulation.
AB  - Cell cycle of Entamoeba histolytica, the etiological agent of amoebiasis, follows
      a novel pathway, which includes nuclear division without the nuclear membrane
      disassembly. We report a nuclear localized Ca2+-binding protein from E.
      histolytica (abbreviated hereafter as EhCaBP6), which is associated with
      microtubules. We determined the 3D solution NMR structure of EhCaBP6, and
      identified one unusual, one canonical and two non-canonical cryptic EF-hand
      motifs. The cryptic EF-II and EF-IV pair with the Ca2+-binding EF-I and EF-III,
      respectively, to form a two-domain structure similar to Calmodulin and Centrin
      proteins. Downregulation of EhCaBP6 affects cell proliferation by causing delays
      in transition from G1 to S phase, and inhibition of DNA synthesis and
      cytokinesis. We also demonstrate that EhCaBP6 modulates microtubule dynamics by
      increasing the rate of tubulin polymerization. Our results, including structural
      inferences, suggest that EhCaBP6 is an unusual CaBP involved in regulating cell
      proliferation in E. histolytica similar to nuclear Calmodulin.

PMID- 28505198
TI  - Strongyloides seroprevalence before and after an ivermectin mass drug
      administration in a remote Australian Aboriginal community.
AB  - BACKGROUND: Strongyloides seroprevalence is hyper-endemic in many Australian
      Aboriginal and Torres Strait Islander communities, ranging from 35-60%. We report
      the impact on Strongyloides seroprevalence after two oral ivermectin mass drug
      administrations (MDAs) delivered 12 months apart in a remote Australian
      Aboriginal community. METHODS: Utilizing a before and after study design, we
      measured Strongyloides seroprevalence through population census with sequential
      MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in
      serostatus. Serodiagnosis was undertaken by ELISA that used sonicated
      Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant
      participants weighing >=15 kg were administered a single 200 MUg/kg ivermectin
      dose, repeated after 10-42 days if Strongyloides and/or scabies was diagnosed;
      others followed a standard alternative algorithm. A questionnaire on clinical
      symptoms was administered to identify adverse events from treatment and self
      reported symptoms associated with serostatus. FINDINGS: We surveyed 1013
      participants at the baseline population census and 1060 (n = 700 from baseline
      cohort and 360 new entrants) at month 12. Strongyloides seroprevalence fell from
      21% (175/818) at baseline to 5% at month 6. For participants from the baseline
      cohort this reduction was sustained at month 12 (34/618, 6%), falling to 2% at
      month 18 after the second MDA. For new entrants to the cohort at month 12,
      seroprevalence reduced from 25% (75/297) to 7% at month 18. Strongyloides
      positive seroconversions for the baseline cohort six months after each MDA were
      2.5% (4/157) at month 6 and 1% at month 18, whilst failure to serorevert remained
      unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline
      seropositive participants and 89% of seropositive new entrants, compared with
      47%baseline seronegative participants and 51% seronegative new entrants.
      Seropositivity was not correlated with haemoglobin or any self-reported clinical
      symptoms. Clinical symptoms ascertained on the day of treatment and 24-72 hrs
      after, did not identify any adverse events. SIGNIFICANCE: Two community
      ivermectin MDAs delivered 12 months apart by trained Aboriginal researchers in
      collaboration with non-Indigenous researchers resulted in a sustained and
      significant reduction in Strongyloides seroprevalence over 18 months. Similar
      reductions were seen in the baseline cohort and new entrants.

PMID- 28505199
TI  - Stress and salivary cortisol in emergency medical dispatchers: A randomized
      shifts control trial.
AB  - Stress at work is a public health concern. Phone operators in emergency medical
      dispatch centers are particularly at risk. We aimed to demonstrate that the most
      stressful time for emergency medical dispatchers is the shift when they receive
      emergency incoming calls, with cortisol as a biomarker of stress. For each
      emergency medical dispatcher, we measured outcomes over a control day and during
      three types of shift: Incoming emergency call, Dispatch and Re-assessment. The
      pattern of shifts was randomized. Saliva was sampled every 15 minutes for 2
      hours, i.e. 6 consecutive times, starting 15 minutes after the first life-and
      death incoming emergency call between 2 and 5 pm during three types of shift. We
      measured saliva cortisol every 2 hours over a control day, from 7am to 9pm.
      Perceived stress was assessed by a visual analog scale. We recruited 22 phone
      operators aged 36.4+/-10.8 years old (14 women and 8 men). Cortisol values were
      higher during the Incoming emergency call shift than during the Dispatch (p =
      .04) and Re-assessment (p = .04) shifts. The increase in cortisol levels was
      greater in men than in women (p = .009). There were no differences between
      control values and those of the three shifts. The kinetics of cortisol increased
      with greater perceived stress overall (p < .001) and for each type of shift
      (Incoming emergency call, p = .02; Dispatch p = .03; Re-assessment: p < .001).
      The kinetics of cortisol in response to incoming emergency calls was greater when
      the call was an absolute emergency (p = .03), and also tended to further increase
      when a subsequent absolute incoming emergency call was received (p = 0.07). In
      conclusion, the incoming emergency call shift carries particular risk for
      dispatchers, who have greater perceived stress and a greater increase in cortisol
      levels.

PMID- 28505200
TI  - Using eDNA to detect the distribution and density of invasive crayfish in the
      Honghe-Hani rice terrace World Heritage site.
AB  - The Honghe-Hani landscape in China is a UNESCO World Natural Heritage site due to
      the beauty of its thousands of rice terraces, but these structures are in danger
      from the invasive crayfish Procambarus clarkii. Crayfish dig nest holes, which
      collapse terrace walls and destroy rice production. Under the current control
      strategy, farmers self-report crayfish and are issued pesticide, but this
      strategy is not expected to eradicate the crayfish nor to prevent their spread
      since farmers are not able to detect small numbers of crayfish. Thus, we tested
      whether environmental DNA (eDNA) from paddy-water samples could provide a
      sensitive detection method. In an aquarium experiment, Real-time Quantitative
      polymerase chain reaction (qPCR) successfully detected crayfish, even at a
      simulated density of one crayfish per average-sized paddy (with one false
      negative). In a field test, we tested eDNA and bottle traps against direct counts
      of crayfish. eDNA successfully detected crayfish in all 25 paddies where crayfish
      were observed and in none of the 7 paddies where crayfish were absent. Bottle
      trapping was successful in only 68% of the crayfish-present paddies. eDNA
      concentrations also correlated positively with crayfish counts. In sum, these
      results suggest that single samples of eDNA are able to detect small crayfish
      populations, but not perfectly. Thus, we conclude that a program of repeated eDNA
      sampling is now feasible and likely reliable for measuring crayfish geographic
      range and for detecting new invasion fronts in the Honghe Hani landscape, which
      would inform regional control efforts and help to prevent the further spread of
      this invasive crayfish.

PMID- 28505201
TI  - Assessment of antibody library diversity through next generation sequencing and
      technical error compensation.
AB  - Antibody libraries are important resources to derive antibodies to be used for a
      wide range of applications, from structural and functional studies to
      intracellular protein interference studies to developing new diagnostics and
      therapeutics. Whatever the goal, the key parameter for an antibody library is its
      complexity (also known as diversity), i.e. the number of distinct elements in the
      collection, which directly reflects the probability of finding in the library an
      antibody against a given antigen, of sufficiently high affinity. Quantitative
      evaluation of antibody library complexity and quality has been for a long time
      inadequately addressed, due to the high similarity and length of the sequences of
      the library. Complexity was usually inferred by the transformation efficiency and
      tested either by fingerprinting and/or sequencing of a few hundred random library
      elements. Inferring complexity from such a small sampling is, however, very
      rudimental and gives limited information about the real diversity, because
      complexity does not scale linearly with sample size. Next-generation sequencing
      (NGS) has opened new ways to tackle the antibody library complexity quality
      assessment. However, much remains to be done to fully exploit the potential of
      NGS for the quantitative analysis of antibody repertoires and to overcome current
      limitations. To obtain a more reliable antibody library complexity estimate here
      we show a new, PCR-free, NGS approach to sequence antibody libraries on Illumina
      platform, coupled to a new bioinformatic analysis and software (Diversity
      Estimator of Antibody Library, DEAL) that allows to reliably estimate the
      complexity, taking in consideration the sequencing error.

PMID- 28505202
TI  - Serum HBV surface antigen positivity is associated with low prevalence of
      metabolic syndrome: A meta-analysis.
AB  - BACKGROUND AND AIM: As there is conflicting evidence for the relationship between
      hepatitis B virus surface antigen (HBsAg) positivity and the prevalence of
      metabolic syndrome (MetS), we performed a meta-analysis to investigate whether
      HBsAg positivity affects the incidence of MetS. METHODS: Observational studies on
      the relationship between HBsAg positivity and MetS were obtained from PubMed, Web
      of Science, and the Cochrane Library in April 2016. The pooled odds ratios (ORs)
      of MetS and its components (central obesity, increased fasting glucose, increased
      blood pressure, dyslipidemia) for subjects with or without HBsAg positivity were
      synthesized. The standardized mean difference of MetS components between HBsAg
      positive participants and healthy controls was calculated. Heterogeneity was
      explored with subgroup analysis and sensitivity analysis. Publication bias was
      detected using Egger's test and Begg's test. RESULTS: Thirty studies were
      eligible for meta-analysis. The MetS OR for HBsAg-positive participants was
      significantly decreased compared with the controls [OR = 0.80, 95% confidence
      interval (CI), 0.70-0.90]. The negative effect of HBsAg positivity on elevated
      triglycerides (OR = 0.62, 95% CI, 0.59-0.64) was strong, while that for increased
      fasting blood glucose was weak (OR = 0.94, 95% CI, 0.90-0.98). The pooled ORs of
      central obesity (OR = 0.97, 95% CI, 0.91-1.04), reduced high-density lipoprotein
      cholesterol (OR = 0.98, 95% CI, 0.83-1.14), and elevated blood pressure (OR =
      1.00, 95% CI, 0.80-1.25) for HBsAg-positive participants were all not
      significantly different compared with the controls. No publication bias was
      detected. CONCLUSIONS: Serum HBsAg positivity is inversely associated with the
      prevalence of MetS. Among the five components of MetS, elevated triglycerides had
      the strongest inverse relationship with HBsAg positivity.

PMID- 28505203
TI  - Cytological and morphological analysis of hybrids between Brassicoraphanus, and
      Brassica napus for introgression of clubroot resistant trait into Brassica napus
      L.
AB  - Interspecific hybridization is a powerful tool for improvement of crop species,
      it has the potential to broaden the genetic base and create new plant forms for
      breeding programs. Synthetic allopolyploid is a widely-used model for the study
      of genetic recombination and fixed heterosis in Brassica. In Brassica napus
      breeding, identification and introgression of new sources of clubroot resistance
      trait from wild or related species into it by hybridization is a long-term crop
      management strategy for clubroot disease. Radish (Raphanus sativus L.) is a close
      relative of the Brassica and most radish accessions are immune to the clubroot
      disease. A synthesized allotetraploid Brassicoraphanus (RRCC, 2n = 36) between R.
      sativus cv. HQ-04 (2n = 18, RR) and Brassica oleracea var. alboglabra (L.H
      Bailey) (2n = 18, CC) proved resistant of multiple clubroot disease pathogen P.
      brassicae. To predict the possibility to transfer the clubroot resistance trait
      from the RR subgenome of allotetraploid Brassicoraphanus (RRCC, 2n = 36) into
      Brassica napus (AACC, 2n = 38), we analyzed the frequency of chromosome pairings
      in the F1 hybrids produced from a cross between B. napus cv. HS5 and the
      allotetraploid, characterize the genomic composition of some backcrossed progeny
      (BC1) using GISH, BAC-FISH and AFLP techniques. The level of intergenomic pairing
      between A and R genomes in the F1 hybrid was high, allosyndetic bivalents formed
      in 73.53% PMCs indicative of significant level of homeologous recombination
      between two genomes and high probability of incorporating chromosomal
      segments/genes from R-genome into A/C-genomes. The BC1 plants inherited variant
      extra R chromosomes or fragments from allotetraploid as revealed by GISH and AFLP
      analysis. 13.51% BC2 individuals were resistant to clubroot disease, and several
      resistance lines had high pollen fertility, Overall, the genetic material
      presented in this work represents a potential new genetic resource for practical
      use in breeding B. napus clubroot resistant cultivars.

PMID- 28505205
TI  - Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse
      pregnancy outcomes in high-risk Taiwanese women.
AB  - BACKGROUND: The objective of this study was to investigate the associations among
      the mid-pregnancy glycated hemoglobin A1c (HbA1c) level, gestational diabetes
      (GDM), and risk of adverse pregnancy outcomes in women without overt diabetes and
      with positive 50-g, 1-h glucose challenge test (GCT) results (140 mg/dL or
      greater). METHODS: This prospective study enrolled 1,989 pregnant Taiwanese
      women. A two-step approach, including a 50-g, 1-h GCT and 100-g, 3-h oral glucose
      tolerance test (OGTT), was employed for the diagnosis of GDM at weeks 23-32. The
      mid-pregnancy HbA1c level was measured at the time the OGTT was performed. A
      receiver operating characteristic (ROC) curve was used to determine the
      relationship between the mid-pregnancy HbA1c level and GDM. Multiple logistic
      regression models were implemented to assess the relationships between the mid
      pregnancy HbA1c level and adverse pregnancy outcomes. RESULTS: An ROC curve
      demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM,
      as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was
      5.7%. The area under the ROC curve of the mid-pregnancy HbA1c level for GDM was
      0.70. Compared with the levels of 4.5-4.9%, higher mid-pregnancy HbA1c levels
      (5.0-5.4, 5.5-5.9, 6.0-6.4, 6.5-6.9, and >7.0%) were significantly associated
      with increased risks of gestational hypertension or preeclampsia, preterm
      delivery, admission to the neonatal intensive care unit, low birth weight, and
      macrosomia (the odds ratio [OR] ranges were 1.20-9.98, 1.31-5.16, 0.88-3.15, 0.89
      4.10, and 2.22-27.86, respectively). CONCLUSIONS: The mid-pregnancy HbA1c level
      was associated with various adverse pregnancy outcomes in high-risk Taiwanese
      women. However, it lacked adequate sensitivity and specificity to replace the two
      step approach in the diagnosis of GDM. The current study comprised a single
      center prospective study; thus, additional, randomized control design studies are
      required.

PMID- 28505204
TI  - Compartment-specific distribution of human intestinal innate lymphoid cells is
      altered in HIV patients under effective therapy.
AB  - Innate lymphocyte cells (ILCs), a novel family of innate immune cells are
      considered to function as key orchestrators of immune defences at mucosal
      surfaces and to be crucial for maintaining an intact intestinal barrier.
      Accordingly, first data suggest depletion of ILCs to be involved in human
      immunodeficiency virus (HIV)-associated damage of the intestinal mucosa and
      subsequent microbial translocation. However, although ILCs are preferentially
      localized at mucosal surfaces, only little is known regarding distribution and
      function of ILCs in the human gastrointestinal tract. Here, we show that in HIV(
      ) individuals composition and functional capacity of intestinal ILCs is
      compartment-specific with group 1 ILCs representing the major fraction in the
      upper gastrointestinal (GI) tract, whereas ILC3 are the predominant population in
      ileum and colon, respectively. In addition, we present first data indicating that
      local cytokine concentrations, especially that of IL-7, might modulate
      composition of gut ILCs. Distribution of intestinal ILCs was significantly
      altered in HIV patients, who displayed decreased frequency of total ILCs in ileum
      and colon owing to reduced numbers of both CD127(+)ILC1 and ILC3. Of note,
      frequency of colonic ILC3 was inversely correlated with serum levels of I-FABP
      and sCD14, surrogate markers for loss of gut barrier integrity and microbial
      translocation, respectively. Both expression of the IL-7 receptor CD127 on ILCs
      as well as mucosal IL-7 mRNA levels were decreased in HIV(+) patients, especially
      in those parts of the GI tract with reduced ILC frequencies, suggesting that
      impaired IL-7 responses of ILCs might contribute to incomplete reconstitution of
      ILCs under effective anti-retroviral therapy. This is the first report comparing
      distribution and function of ILCs along the intestinal mucosa of the entire human
      gastrointestinal tract in HIV(+) and HIV(-) individuals.

PMID- 28505206
TI  - Effects of alphaTAT1 and HDAC5 on axonal regeneration in adult neurons.
AB  - The role of posttranslational modifications in axonal injury and regeneration has
      been widely studied but there has been little consensus over the mechanism by
      which each modification affects adult axonal growth. Acetylation is known to play
      an important role in a variety of neuronal functions and its homeostasis is
      controlled by two enzyme families: the Histone Deacetylases (HDACs) and Histone
      Acetyl Transferases (HATs). Recent studies show that HDAC5 deacetylates
      microtubules in the axonal cytoplasm as part of an injury-induced regeneration
      response, but little is known about how acetylation of microtubules plays a role.
      Alpha-tubulin acetyl transferase (alphaTAT1) is a microtubule specific acetyl
      transferase that binds to microtubules and directly affects microtubule stability
      in cells. We hypothesize that increasing tubulin acetylation may play an
      important role in increasing the rate of axonal growth. In this study, we
      infected cultured adult DRG neurons with alphaTAT1 and alphaTAT1-D157N, a
      catalytically inactive mutant, and HDAC5, using lentiviruses. We found that
      alphaTAT1 significantly increases tubulin acetylation in 293T cells and DRG
      neurons but alphaTAT1-D157N does not. Furthermore, in neurons infected with
      alphaTAT1, a significant increase in acetylated tubulin was detected towards the
      distal portion of the axon but this increase was not detected in neurons infected
      with alphaTAT1-D157N. However, we found a significant increase in axon lengths of
      DRG neurons after alphaTAT1 and alphaTAT1-D157N infection, but no effect on axon
      lengths after infection with HDAC5. Our results suggest that while alphaTAT1 may
      play a role in axon growth in vitro, the increase is not directly due to
      acetylation of axonal microtubules. Our results also show that HDAC5
      overexpression in the axonal cytoplasm does not play a crucial role in axonal
      regeneration of cultured DRG neurons. We expressed these genes in DRG neurons in
      adult rats and performed a sciatic nerve crush. We found that axons did not
      regenerate any better when infected with any of the constructs compared with
      control animals. Thus, while alphaTAT1 may be important for axonal growth in
      vitro, neither alphaTAT1 nor HDAC5 had an effect in vivo on the regeneration of
      sciatic nerves.

PMID- 28505208
TI  - Neuromuscular function of the quadriceps muscle during isometric maximal,
      submaximal and submaximal fatiguing voluntary contractions in knee osteoarthrosis
      patients.
AB  - INTRODUCTION: Knee osteoarthrosis (KOA) is commonly associated with a dysfunction
      of the quadriceps muscle which contributes to alterations in motor performance.
      The underlying neuromuscular mechanisms of muscle dysfunction are not fully
      understood. The main objective of this study was to analyze how KOA affects
      neuromuscular function of the quadriceps muscle during different contraction
      intensities. MATERIALS AND METHODS: The following parameters were assessed in 20
      patients and 20 healthy controls: (i) joint position sense, i.e. position control
      (mean absolute error, MAE) at 30 degrees  and 50 degrees  of knee flexion, (ii)
      simple reaction time task performance, (iii) isometric maximal voluntary torque
      (IMVT) and root mean square of the EMG signal (RMS-EMG), (iv) torque control,
      i.e. accuracy (MAE), absolute fluctuation (standard deviation, SD), relative
      fluctuation (coefficient of variation, CV) and periodicity (mean frequency, MNF)
      of the torque signal at 20%, 40% and 60% IMVT, (v) EMG-torque relationship at
      20%, 40% and 60% IMVT and (vi) performance fatigability, i.e. time to task
      failure (TTF) at 40% IMVT. RESULTS: Compared to the control group, the KOA group
      displayed: (i) significantly higher MAE of the angle signal at 30 degrees 
      (99.3%; P = 0.027) and 50 degrees  (147.9%; P < 0.001), (ii) no significant
      differences in reaction time, (iii) significantly lower IMVT (-41.6%; P = 0.001)
      and tendentially lower RMS-EMG of the rectus femoris (-33.7%; P = 0.054), (iv)
      tendentially higher MAE of the torque signal at 20% IMVT (65.9%; P = 0.068),
      significantly lower SD of the torque signal at all three torque levels and
      greater MNF at 60% IMVT (44.8%; P = 0.018), (v) significantly increased RMS-EMG
      of the vastus lateralis at 20% (70.8%; P = 0.003) and 40% IMVT (33.3%; P =
      0.034), significantly lower RMS-EMG of the biceps femoris at 20% (-63.6%; P =
      0.044) and 40% IMVT (-41.3%; P = 0.028) and tendentially lower at 60% IMVT (
      24.3%; P = 0.075) and (vi) significantly shorter TTF (-51.1%; P = 0.049).
      CONCLUSION: KOA is not only associated with a deterioration of IMVT and
      neuromuscular activation, but also with an impaired position and torque control
      at submaximal torque levels, an altered EMG-torque relationship and a higher
      performance fatigability of the quadriceps muscle. It is recommended that the
      rehabilitation includes strengthening and fatiguing exercises at maximal and
      submaximal force levels.

PMID- 28505207
TI  - Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case
      control study.
AB  - A small proportion of women who are exposed to infection with human
      papillomavirus (HPV) develop cervical cancer (CC). Genetic factors may affect the
      risk of progression from HPV infection to cervical precancer and cancer. We used
      samples from the International Agency for Research on Cancer (IARC) multicentric
      case-control study to evaluate the association of selected genetic variants with
      CC. Overall, 790 CC cases and 717 controls from Algeria, Morocco, India and
      Thailand were included. Cervical exfoliated cells were obtained from control
      women and cervical exfoliated cells or biopsy specimens from cases. HPV
      positivity was determined using a general primer GP5+/6+ mediated PCR.
      Unconditional logistic regression was used to estimate odds ratios (OR) and
      corresponding 95% confidence intervals (CI) of host genotypes with CC risk, using
      the homozygous wild type genotype as the referent category and adjusting by age
      and study centre. The association of polymorphisms with the risk of high-risk HPV
      positivity among controls was also evaluated. A statistically significant
      association was observed between single nucleotide polymorphism (SNP) CHR6
      rs2844511 and CC risk: the OR for carriers of the GA or GG genotypes was 0.70
      (95% CI: 0.43-1.14) and 0.61 (95% CI: 0.38-0.98), respectively, relative to
      carriers of AA genotype (p-value for trend 0.03). We also observed associations
      of borderline significance with the TIPARP rs2665390 polymorphism, which was
      previously found to be associated with ovarian and breast cancer, and with the
      EXOC1 rs13117307 polymorphism, which has been linked to cervical cancer in a
      large study in a Chinese population. We confirmed the association between CC and
      the rs2844511 polymorphism previously identified in a GWAS study in a Swedish
      population. The major histocompatibility region of chromosome 6, or perhaps other
      SNPs in linkage disequilibrium, may be involved in CC onset.

PMID- 28505209
TI  - Genetic identification and evolutionary trends of the seagrass Halophila
      nipponica in temperate coastal waters of Korea.
AB  - Although seagrass species in the genus Halophila are generally distributed in
      tropical or subtropical regions, H. nipponica has been reported to occur in
      temperate coastal waters of the northwestern Pacific. Because H. nipponica occurs
      only in the warm temperate areas influenced by the Kuroshio Current and shows a
      tropical seasonal growth pattern, such as severely restricted growth in low water
      temperatures, it was hypothesized that this temperate Halophila species diverged
      from tropical species in the relatively recent evolutionary past. We used a
      phylogenetic analysis of internal transcribed spacer (ITS) regions to examine the
      genetic variability and evolutionary trend of H. nipponica. ITS sequences of H.
      nipponica from various locations in Korea and Japan were identical or showed very
      low sequence divergence (less than 3-base pair, bp, difference), confirming that
      H. nipponica from Japan and Korea are the same species. Halophila species in the
      section Halophila, which have simple phyllotaxy (a pair of petiolate leaves at
      the rhizome node), were separated into five well-supported clades by maximum
      parsimony analysis. H. nipponica grouped with H. okinawensis and H. gaudichaudii
      from the subtropical regions in the same clade, the latter two species having
      quite low ITS sequence divergence from H. nipponica (7-15-bp). H. nipponica in
      Clade I diverged 2.95 +/- 1.08 million years ago from species in Clade II, which
      includes H. ovalis. According to geographical distribution and genetic
      similarity, H. nipponica appears to have diverged from a tropical species like H.
      ovalis and adapted to warm temperate environments. The results of divergence time
      estimates suggest that the temperate H. nipponica is an older species than the
      subtropical H. okinawensis and H. gaudichaudii and they may have different
      evolutionary histories.

PMID- 28505210
TI  - Whole exome sequencing of a consanguineous family identifies the possible
      modifying effect of a globally rare AK5 allelic variant in celiac disease
      development among Saudi patients.
AB  - Celiac disease (CD), a multi-factorial auto-inflammatory disease of the small
      intestine, is known to occur in both sporadic and familial forms. Together HLA
      and Non-HLA genes can explain up to 50% of CD's heritability. In order to
      discover the missing heritability due to rare variants, we have exome sequenced a
      consanguineous Saudi family presenting CD in an autosomal recessive (AR) pattern.
      We have identified a rare homozygous insertion c.1683_1684insATT, in the
      conserved coding region of AK5 gene that showed classical AR model segregation in
      this family. Sequence validation of 200 chromosomes each of sporadic CD cases and
      controls, revealed that this extremely rare (EXac MAF 0.000008) mutation is
      highly penetrant among general Saudi populations (MAF is 0.62). Genotype and
      allelic distribution analysis have indicated that this AK5 (c.1683_1684insATT)
      mutation is negatively selected among patient groups and positively selected in
      the control group, in whom it may modify the risk against CD development
      [p<0.002]. Our observation gains additional support from computational analysis
      which predicted that Iso561 insertion shifts the existing H-bonds between 400th
      and 556th amino acid residues lying near the functional domain of adenylate
      kinase. This shuffling of amino acids and their H-bond interactions is likely to
      disturb the secondary structure orientation of the polypeptide and induces the
      gain-of-function in nucleoside phosphate kinase activity of AK5, which may
      eventually down-regulates the reactivity potential of CD4+ T-cells against gluten
      antigens. Our study underlines the need to have population-specific genome
      databases to avoid false leads and to identify true candidate causal genes for
      the familial form of celiac disease.

PMID- 28505212
TI  - Disentangling niche competition from grazing mortality in phytoplankton dilution
      experiments.
AB  - The dilution method is the principal tool used to infer in situ microzooplankton
      grazing rates. However, grazing is the only mortality process considered in the
      theoretical model underlying the interpretation of dilution method experiments.
      Here we evaluate the robustness of mortality estimates inferred from dilution
      experiments when there is concurrent niche competition amongst phytoplankton.
      Using a combination of mathematical analysis and numerical simulations, we find
      that grazing rates may be overestimated-the degree of overestimation is related
      to the importance of niche competition relative to microzooplankton grazing. In
      response, we propose a conceptual method to disentangle the effects of niche
      competition and grazing by diluting out microzooplankton, but not phytoplankton.
      Our theoretical results suggest this revised "Z-dilution" method can robustly
      infer grazing mortality, regardless of the dominant phytoplankton mortality
      driver in our system. Further, we show it is possible to independently estimate
      both grazing mortality and niche competition if the classical and Z-dilution
      methods can be used in tandem. We discuss the significance of these results for
      quantifying phytoplankton mortality rates; and the feasibility of implementing
      the Z-dilution method in practice, whether in model systems or in complex
      communities with overlap in the size distributions of phytoplankton and
      microzooplankton.

PMID- 28505213
TI  - Dupuytren's disease: How to recognize its early signs.
AB  - Palmar skin dimpling and nodule or cord formation signal advancing disease.
      Treatments vary in effectiveness--in part, depending on condition severity.

PMID- 28505214
TI  - Publication and Reporting of the Results of Postmarket Studies for Drugs Required
      by the US Food and Drug Administration, 2009 to 2013.

PMID- 28505216
TI  - Could Albumin Be a Biomarker to Monitor the Effect of Intravenous Immunoglobulin
      on Guillain-Barre Syndrome?

PMID- 28505211
TI  - Fronto-temporal interactions are functionally relevant for semantic control in
      language processing.
AB  - Semantic cognition, i.e. processing of meaning is based on semantic
      representations and their controlled retrieval. Semantic control has been shown
      to be implemented in a network that consists of left inferior frontal (IFG), and
      anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt
      semantic control processes with continuous theta burst stimulation (cTBS) over
      left IFG and pMTG and to study whether behavioral effects are moderated by
      induced alterations in resting-state functional connectivity. To this end, we
      applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20
      healthy participants in a within-subject design. Stimulation was followed by
      resting-state functional magnetic resonance imaging and a semantic priming
      paradigm. Resting-state functional connectivity of regions of interest in left
      IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto
      temporal networks representing the semantic system. We did not find any
      significant direct modulation of either task performance or resting-state
      functional connectivity by effective cTBS. However, after sham cTBS, functional
      connectivity between IFG and pMTG correlated with task performance under high
      semantic control demands in the semantic priming paradigm. These findings provide
      evidence for the functional relevance of interactions between IFG and pMTG for
      semantic control processes. This interaction was functionally less relevant after
      cTBS over aIFG which might be interpretable in terms of an indirect disruptive
      effect of cTBS.

PMID- 28505215
TI  - Patient Dismissal by Primary Care Practices.

PMID- 28505218
TI  - Establishing and Achieving National Goals for Preventing Lead Toxicity and
      Exposure in Children.

PMID- 28505217
TI  - Effect of Combined Patient Decision Aid and Patient Navigation vs Usual Care for
      Colorectal Cancer Screening in a Vulnerable Patient Population: A Randomized
      Clinical Trial.
AB  - Importance: Colorectal cancer (CRC) screening is underused, especially among
      vulnerable populations. Decision aids and patient navigation are potentially
      complementary interventions for improving CRC screening rates, but their combined
      effect on screening completion is unknown. Objective: To determine the combined
      effect of a CRC screening decision aid and patient navigation compared with usual
      care on CRC screening completion. Design, Setting, and Participants: In this
      randomized clinical trial, data were collected from January 2014 to March 2016 at
      2 community health center practices, 1 in North Carolina and 1 in New Mexico,
      serving vulnerable populations. Patients ages 50 to 75 years who had average CRC
      risk, spoke English or Spanish, were not current with recommended CRC screening,
      and were attending primary care visits were recruited and randomized 1:1 to
      intervention or control arms. Interventions: Intervention participants viewed a
      CRC screening decision aid in English or Spanish immediately before their
      clinician encounter. The decision aid promoted screening and presented
      colonoscopy and fecal occult blood testing as screening options. After the
      clinician encounter, intervention patients received support for screening
      completion from a bilingual patient navigator. Control participants viewed a food
      safety video before the encounter and otherwise received usual care. Main
      Outcomes and Measures: The primary outcome was CRC screening completion within 6
      months of the index study visit assessed by blinded medical record review.
      Results: Characteristics of the 265 participants were as follows: their mean age
      was 58 years; 173 (65%) were female, 164 (62%) were Latino; 40 (15%) were white
      non-Latino; 61 (23%) were black or of mixed race; 191 (78%) had a household
      income of less than $20 000; 101 (38%) had low literacy; 75 (28%) were on
      Medicaid; and 91 (34%) were uninsured. Intervention participants were more likely
      to complete CRC screening within 6 months (68% vs 27%); adjusted-difference, 40
      percentage points (95% CI, 29-51 percentage points). The intervention was more
      effective in women than in men (50 vs 21 percentage point increase, interaction P
      = .02). No effect modification was observed across other subgroups. Conclusions
      and Relevance: A patient decision aid plus patient navigation increased the rate
      of CRC screening completion in compared with usual care invulnerable primary care
      patients. Trial Registration: clinicaltrials.gov Identifier: NCT02054598.

PMID- 28505219
TI  - 64Cu-DOTA-trastuzumab PET imaging for HER2-specific primary lesions of breast
      cancer.

PMID- 28505220
TI  - Multicenter Evaluation of the Bruker MALDI Biotyper CA System for the
      Identification of Clinically Important Bacteria and Yeasts.
AB  - Objectives: A report on the multicenter evaluation of the Bruker MALDI Biotyper
      CA System (MBT-CA; Bruker Daltonics, Billerica, MA) for the identification of
      clinically important bacteria and yeasts. Methods: In total, 4,399 isolates of
      medically important bacteria and yeasts were assessed in the MBT-CA. These
      included 2,262 aerobic gram-positive (AGP) bacteria, 792 aerobic gram-negative
      (AGN) bacteria 530 anaerobic (AnA) bacteria, and 815 yeasts (YSTs). Three
      processing methods were assesed. Results: Overall, 98.4% (4,329/4,399) of all
      bacterial and yeast isolates were correctly identified to the genus and
      species/species complex level, and 95.7% of isolates were identified with a high
      degree of confidence. The percentage correctly identified and the percentage
      identified correctly with a high level of confidence, respectively, were as
      follows: AGP bacteria (98.6%/96.5%), AGN bacteria (98.5%/96.8%), AnA bacteria
      (98.5%/97.4%), and YSTs (97.8%/87.6%). The extended direct transfer method was
      only minimally superior to the direct transfer method for bacteria (89.9% vs
      86.8%, respectively) but significantly superior for yeast isolates (74.0% vs
      48.9%, respectively). Conclusions: The Bruker MALDI Biotyper CA System accurately
      identifies most clinically important bacteria and yeasts and has optional
      processing methods to improve isolate characterization.

PMID- 28505221
TI  - Combining PI3K and PARP inhibitors for breast and ovarian cancer treatment.

PMID- 28505222
TI  - Discourse Characteristics in Aphasia Beyond the Western Aphasia Battery Cutoff.
AB  - Purpose: This study examined discourse characteristics of individuals with
      aphasia who scored at or above the 93.8 cutoff on the Aphasia Quotient subtests
      of the Western Aphasia Battery-Revised (WAB-R; Kertesz, 2007). They were compared
      with participants without aphasia and those with anomic aphasia. Method:
      Participants were from the AphasiaBank database and included 28 participants who
      were not aphasic by WAB-R score (NABW), 92 participants with anomic aphasia, and
      177 controls. Cinderella narratives were analyzed using the Computerized Language
      Analysis programs (MacWhinney, 2000). Outcome measures were words per minute,
      percent word errors, lexical diversity using the moving average type-token ratio
      (Covington, 2007b), main concept production, number of utterances, mean length of
      utterance, and proposition density. Results: Results showed that the NABW group
      was significantly different from the controls on all measures except MLU and
      proposition density. These individuals were compared to participants without
      aphasia and those with anomic aphasia. Conclusion: Individuals with aphasia who
      score above the WAB-R Aphasia Quotient cutoff demonstrate discourse impairments
      that warrant both treatment and special attention in the research literature.

PMID- 28505224
TI  - Muscle Bioenergetic Considerations for Intrinsic Laryngeal Skeletal Muscle
      Physiology.
AB  - Purpose: Intrinsic laryngeal skeletal muscle bioenergetics, the means by which
      muscles produce fuel for muscle metabolism, is an understudied aspect of
      laryngeal physiology with direct implications for voice habilitation and
      rehabilitation. The purpose of this review is to describe bioenergetic pathways
      identified in limb skeletal muscle and introduce bioenergetic physiology as a
      necessary parameter for theoretical models of laryngeal skeletal muscle function.
      Method: A comprehensive review of the human intrinsic laryngeal skeletal muscle
      physiology literature was conducted. Findings regarding intrinsic laryngeal
      muscle fiber complement and muscle metabolism in human models are summarized and
      exercise physiology methodology is applied to identify probable bioenergetic
      pathways used for voice function. Results: Intrinsic laryngeal skeletal muscle
      fibers described in human models support the fast, high-intensity physiological
      requirements of these muscles for biological functions of airway protection.
      Inclusion of muscle bioenergetic constructs in theoretical modeling of voice
      training, detraining, fatigue, and voice loading have been limited. Conclusions:
      Muscle bioenergetics, a key component for muscle training, detraining, and
      fatigue models in exercise science, is a little-considered aspect of intrinsic
      laryngeal skeletal muscle physiology. Partnered with knowledge of occupation
      specific voice requirements, application of bioenergetics may inform novel
      considerations for voice habilitation and rehabilitation.

PMID- 28505223
TI  - Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals
      With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE
      Cohort.
AB  - Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS)
      vary. The significance of this variation is unclear. Specifically, to our
      knowledge, the shortest effective administration-to-birth interval is unknown.
      Objective: To explore the associations between ANS administration-to-birth
      interval and survival and morbidity among very preterm infants. Design, Setting,
      and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study,
      a population-based prospective cohort study, gathered data from 19 regions in 11
      European countries in 2011 and 2012 on 4594 singleton infants with gestational
      ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated
      courses of ANS. Data were analyzed November 2016. Exposure: Time from first
      injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three
      outcomes were studied: in-hospital mortality; a composite of mortality or severe
      neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or
      greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis,
      or stage 3 or greater retinopathy of prematurity; and severe neonatal brain
      injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic
      periventricular leukomalacia. Results: Of the 4594 infants included in the
      cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was
      28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the
      662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of
      ANS was associated with an immediate and rapid decline in mortality, reaching a
      plateau with more than 50% risk reduction after an administration-to-birth
      interval of 18 to 36 hours. A similar pattern for timing was seen for the
      composite mortality or morbidity outcome, whereas a significant risk reduction of
      severe neonatal brain injury was associated with longer administration-to-birth
      intervals (greater than 48 hours). For all outcomes, the risk reduction
      associated with ANS was transient, with increasing mortality and risk for severe
      neonatal brain injury associated with administration-to-birth intervals exceeding
      1 week. Under the assumption of a causal relationship between timing of ANS and
      mortality, a simulation of ANS administered 3 hours before delivery to infants
      who did not receive ANS showed that their estimated decline in mortality would be
      26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even
      if given only hours before delivery. Therefore, the infants of pregnant women at
      risk of imminent preterm delivery may benefit from its use.

PMID- 28505226
TI  - OMTools: a software package for visualizing and processing optical mapping data.
AB  - Summary: Optical mapping is a molecular technique capturing specific patterns of
      fluorescent labels along DNA molecules. It has been widely applied in assisted
      scaffolding in sequence assemblies, microbial strain typing and detection of
      structural variations. Various computational methods have been developed to
      analyze optical mapping data. However, existing tools for processing and
      visualizing optical map data still have many shortcomings. Here, we present
      OMTools, an efficient and intuitive data processing and visualization suite to
      handle and explore large-scale optical mapping profiles. OMTools includes modules
      for visualization (OMView), data processing and simulation. These modules
      together form an accessible and convenient pipeline for optical mapping analyses.
      Availability and implementation: OMTools is implemented in Java 1.8 and released
      under a GPL license. OMTools can be downloaded from
      https://github.com/aldenleung/OMTools and run on any standard desktop computer
      equipped with a Java virtual machine. Contact: kevinyip@cse.cuhk.edu.hk or
      tf.chan@cuhk.edu.hk. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 28505225
TI  - Original Findings and Updated Meta-Analysis for the Association Between Maternal
      Diabetes and Risk for Congenital Heart Disease Phenotypes.
AB  - Maternal diabetes is associated with congenital heart defects (CHDs) as a group,
      but few studies have assessed risk for specific CHD phenotypes. We analyzed these
      relationships using data from the Texas Birth Defects Registry and statewide
      vital records for deliveries taking place in 1999-2009 (n = 48,249 cases). We
      used Poisson regression to calculate prevalence ratios for the associations
      between maternal diabetes (pregestational or gestational) and each CHD phenotype,
      adjusting for potential confounders. Analyses were repeated by type of diabetes.
      To address the potential for misclassification bias, we performed logistic
      regression, using malformed controls. We also conducted meta-analyses, combining
      our estimates of the association between pregestational diabetes and each CHD
      phenotype with previous estimates. The prevalence of every CHD phenotype was
      greater among women with pregestational diabetes than among nondiabetic women.
      Most of these differences were statistically significant (adjusted prevalence
      ratios = 2.47-13.20). Associations were slightly attenuated for many CHD
      phenotypes among women with gestational diabetes. The observed associations did
      not appear to be the result of misclassification bias. In our meta-analysis,
      pregestational diabetes was significantly associated with each CHD phenotype.
      These findings contribute to a better understanding of the teratogenic effects of
      maternal diabetes and improved counseling for risk of specific CHD phenotypes.

PMID- 28505227
TI  - Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of
      Skeletal Muscle in Older Men and Women.
AB  - Older men (n = 12) and women (n = 18) 65-80 years of age completed 12 weeks of
      exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the
      hypothesis that RSV treatment combined with exercise would increase mitochondrial
      density, muscle fatigue resistance, and cardiovascular function more than
      exercise alone. Contrary to our hypothesis, aerobic and resistance exercise
      coupled with RSV treatment did not reduce cardiovascular risk further than
      exercise alone. However, exercise added to RSV treatment improved the indices of
      mitochondrial density, and muscle fatigue resistance more than placebo and
      exercise treatments. In addition, subjects that were treated with RSV had an
      increase in knee extensor muscle peak torque (8%), average peak torque (14%), and
      power (14%) after training, whereas exercise did not increase these parameters in
      the placebo-treated older subjects. Furthermore, exercise combined with RSV
      significantly improved mean fiber area and total myonuclei by 45.3% and 20%,
      respectively, in muscle fibers from the vastus lateralis of older subjects.
      Together, these data indicate a novel anabolic role of RSV in exercise-induced
      adaptations of older persons and this suggests that RSV combined with exercise
      might provide a better approach for reversing sarcopenia than exercise alone.

PMID- 28505230
TI  - Degradation and Impurity Profile Study of Ciclopirox Olamine after Pre-column
      Derivatization: A Risk Based Approach.
AB  - The present study focus on ICH prescribed stress degradation of ciclopirox
      olamine after precolumn derivatization. For establishing stability-indicating
      assay, the reaction solutions in which different degradation products were formed
      were mixed, and the separation was optimized by applying principle of QbD. A risk
      analysis tools based on cause-effect risk assessment matrix with control-noise
      experimentation (CNX) approach was utilized for identifying the high risk
      variable affecting the analytical attributes. Plackett Burman and central
      composite design was then used to screen and optimize experimental variables for
      DOE studies to resolve ciclopirox olamine and four of its degradation related
      impurities with good peak asymmetry and theoretical plates using C18 column. The
      method was validated according to ICH and ISO guidelines. To ensure reliability
      of the result, evaluation of risk profile, combined standard uncertainty and
      expanded uncertainty were also studied. One process related and four unknown
      degradation products were identified and characterized by LC-MS/MS study. The
      degradation pathways of degradants were proposed based on m/z values.

PMID- 28505228
TI  - Associations of Musculoskeletal Pain With Mobility in Older Adults: Potential
      Cerebral Mechanisms.
AB  - Background: Musculoskeletal pain is highly prevalent and limits mobility in older
      adults. A potential mechanism by which pain affects mobility could be through its
      negative impact on the brain. We examined whether structural integrity of
      cerebral gray and white matter (WM) mediated the relationship between pain and
      mobility in community-dwelling older adults. Methods: Musculoskeletal pain, gait
      speed, and neuroimaging data were obtained concurrently from the Health ABC study
      (mean age = 83/56% female, n = 212). Microstructural gray matter integrity was
      measured by mean diffusivity (MD), WM microstructure and macrostructure were
      measured by fractional anisotropy (FA) and WM hyperintensities (WMH),
      respectively. Regression models were adjusted for gray matter atrophy, age,
      gender, medication use, and obesity. Bootstrapped mediation methods were used
      (1,000 bootstrapped samples, 95% confidence intervals). Results: The associations
      of musculoskeletal pain with WMH (beta = .19, p < .05) and FA (beta = -.18, p <
      .05) were robust to adjustment for gender, medication use, age, body mass index
      (BMI), and brain atrophy. Participants who experienced both knee and back pain
      had a significantly slower gait speed (~0.11 m/s) than those without knee or back
      pain (p < .05) independent of gender, medication, age, and BMI. WMH and FA
      significantly mediated the pain-gait speed relationship. Associations between
      pain and MD were not significant, and MD did not modify the association between
      pain and gait speed. Conclusions: Cerebral WM integrity may contribute to the
      detrimental effects of musculoskeletal pain on mobility, although pre-existing WM
      integrity may also simultaneously amplify pain and decrease mobility. Future
      studies are needed to further understand whether successful pain management may
      significantly improve both brain health and mobility.

PMID- 28505229
TI  - Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and
      Spine Density in the Adult Mouse Motor Cortex.
AB  - Nogo-A has been well described as a myelin-associated inhibitor of neurite
      outgrowth and functional neuroregeneration after central nervous system (CNS)
      injury. Recently, a new role of Nogo-A has been identified as a negative
      regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in
      neurons and oligodendrocytes. However, it is yet unclear which of these two pools
      regulate synaptic plasticity. To address this question we used newly generated
      mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes
      (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both
      oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic
      branching and spine densities in layer 2/3 cortical pyramidal neurons. These
      effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas
      oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser
      scanning microscopy to measure the spine turnover rate of adult mouse motor
      cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine
      remodeling after 4 days. Our results suggest relevant control functions of glial
      as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for
      more selective and targeted plasticity enhancing strategies.

PMID- 28505231
TI  - Autologous Stem Cell Transplantation for Refractory Crohn's Disease: Is it Time
      to Take a Long-Term View?

PMID- 28505232
TI  - Findings of an Observational Study of Neuraminidase Inhibitors Highly Sensitive
      to Decision to Exclude 1652 Treated Patients.

PMID- 28505233
TI  - Addition of droperidol to prophylactic ondansetron and dexamethasone in children
      at high risk for postoperative vomiting. A randomized, controlled, double-blind
      study.
AB  - Background: : The combination of dexamethasone (DEX), ondansetron (OND) and
      droperidol (DRO) is efficacious in preventing postoperative nausea and vomiting
      in adults, but has not been well assessed in children. Methods: : Children
      undergoing elective surgery under general anaesthesia and considered at high risk
      for postoperative vomiting (POV) were randomly assigned to receive a combination
      of DEX, OND and placebo (Group A) or a combination of DEX, OND and DRO (Group B).
      The primary outcome was the incidence of POV during the first 24 hours after
      surgery. We hypothesized that the addition of DRO to the standard antiemetic
      prophylaxis would provide a further 15% reduction in the residual risk for POV.
      The secondary outcome considered was any adverse event occurring during the
      study. Results: : One hundred and fifty-three children, aged three to 16 years,
      were randomized to Group A and 162 to Group B. The overall incidence of POV did
      not differ significantly between the two groups, with 16 patients in Group A
      (10.5%) and 18 in Group B (11.1%) presenting with one or more episodes of POV, P
      =0.86. Fewer patients presented with adverse events in Group A (2%) compared with
      Group B (8%), P =0.01. Drowsiness and headache were the principal adverse events
      reported. Conclusions: : The addition of DRO to a combination of OND and DEX did
      not decrease POV frequency below that obtained with the two-drug combination in
      children at high risk of POV, but increased the risk of drowsiness. The
      combination of DEX and OND should be recommended in children with a high risk of
      POV. Clinical trial registration.: NCT01739985.

PMID- 28505235
TI  - View-Independent Working Memory Representations of Artificial Shapes in
      Prefrontal and Posterior Regions of the Human Brain.
AB  - Traditional views of visual working memory postulate that memorized contents are
      stored in dorsolateral prefrontal cortex using an adaptive and flexible code. In
      contrast, recent studies proposed that contents are maintained by posterior brain
      areas using codes akin to perceptual representations. An important question is
      whether this reflects a difference in the level of abstraction between posterior
      and prefrontal representations. Here, we investigated whether neural
      representations of visual working memory contents are view-independent, as
      indicated by rotation-invariance. Using functional magnetic resonance imaging and
      multivariate pattern analyses, we show that when subjects memorize complex
      shapes, both posterior and frontal brain regions maintain the memorized contents
      using a rotation-invariant code. Importantly, we found the representations in
      frontal cortex to be localized to the frontal eye fields rather than dorsolateral
      prefrontal cortices. Thus, our results give evidence for the view-independent
      storage of complex shapes in distributed representations across posterior and
      frontal brain regions.

PMID- 28505234
TI  - Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the
      United States, 2012-2015.
AB  - Background: Several clusters of serogroup C meningococcal disease among men who
      have sex with men (MSM) have been reported in the United States in recent years.
      The epidemiology and risk of meningococcal disease among MSM is not well
      described. Methods: All meningococcal disease cases among men aged 18-64 years
      reported to the National Notifiable Disease Surveillance System between January
      2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases
      among MSM and men not known to be MSM (non-MSM) were described. Annualized
      incidence rates among MSM and non-MSM were compared through calculation of the
      relative risk and 95% confidence intervals. Isolates from meningococcal disease
      cases among MSM were characterized using standard microbiological methods and
      whole-genome sequencing. Results: Seventy-four cases of meningococcal disease
      were reported among MSM and 453 among non-MSM. Annualized incidence of
      meningococcal disease among MSM was 0.56 cases per 100000 population, compared to
      0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1
      5.1). Among the 64 MSM with known status, 38 (59%) were infected with human
      immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6)
      the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were
      serogroup C sequence type 11. Conclusions: MSM are at increased risk for
      meningococcal disease, although the incidence of disease remains low. HIV
      infection may be an important factor for this increased risk. Routine vaccination
      of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in
      accordance with Advisory Committee on Immunization Practices recommendations
      should be encouraged.

PMID- 28505237
TI  - Erratum.

PMID- 28505236
TI  - Could Albumin be a Biomarker to Monitor the Effect of Intravenous Immunoglobulin
      on Guillain-Barre Syndrome?-Reply.

PMID- 28505238
TI  - Analysis of Species, Subgroups, and Endosymbionts of Bemisia tabaci (Hemiptera:
      Aleyrodidae) From Southwestern Cotton Fields in Turkey.
AB  - Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is one of the most important
      insect pests worldwide including Turkey. Although there are substantial data
      regarding species composition of Turkish B. tabaci populations, the situation is
      still not clear and further investigations are needed. Therefore, in this study,
      species and subgroups of B. tabaci collected from cotton fields in southwestern
      part of Turkey (Antalya, Aydin, Denizli, and Mugla) were determined using
      microsatellite analysis, AluI-based mtCOI polymerase chain reaction-random length
      polymorphism, and sequencing. Secondary endosymbionts were also determined using
      diagnostic species-specific PCR. Middle East Asia Minor 1 (MEAM1), Mediterranean
      (MED) Q1, and MED Q2 were the species and subgroups found in this study. The MED
      species (85.3%) were found to be more dominant than MEAM1. Species status of B.
      tabaci varied depending on the location. Although all samples collected from
      Aydin were found to be Q1, three species and subgroups were found in Mugla.
      Secondary endosymbionts varied according to species and subgroups. Arsenophonus
      was found only from Q2, while Hamiltonella was detected in MEAM1 and Q1. In
      addition, high Rickettsia and low Wolbachia infections were detected in MEAM1 and
      Q1 populations, respectively. In conclusion, for the first time, we report the
      presence and symbiotic communities of Q1 from Turkey. We also found that the
      symbiont complement of the Q1 is more congruent with Q1 from Greece than other
      regions of the world, which may have some interesting implications for movement
      of this invasive subgroup.

PMID- 28505239
TI  - FoxO1 Promotes Mitophagy in the Podocytes of Diabetic Male Mice via the
      PINK1/Parkin Pathway.
AB  - We recently showed that forkhead-box class O1 (FoxO1) activation protects against
      high glucose-induced injury by preventing mitochondrial dysfunction in the rat
      kidney cortex. In addition, FoxO1 has been reported to mediate putative kinase 1
      (PINK1) transcription and promote autophagy in response to mitochondrial
      oxidative stress in murine cardiomyocytes. In this study, we ascertained whether
      overexpressing FoxO1 in the kidney cortex reverses preestablished diabetic
      nephropathy in animal models. The effect of FoxO1 on mitophagy signaling pathways
      was evaluated in mouse podocytes. In vivo experiments were performed in male KM
      mice. A mouse model of streptozotocin (STZ)-induced type 1 diabetes (T1D) was
      used, and lentiviral vectors were injected into the kidney cortex to overexpress
      FoxO1. A mouse podocyte cell line was treated with high concentrations of glucose
      and genetically modified using lentiviral vectors. We found aberrant
      mitochondrial morphology and reduced adenosine triphosphate production. These
      mitochondrial abnormalities were due to decreased mitophagy via reduced
      phosphatase/tensin homolog on chromosome 10-induced PINK1/Parkin-dependent
      signaling. FoxO1 upregulation and PINK1/Parkin pathway activation can
      individually restore injured podocytes in STZ-induced T1D mice. Our results link
      the antioxidative activity of FoxO1 with PINK1/Parkin-induced mitophagy,
      indicating a novel role of FoxO1 in diabetic nephropathy.

PMID- 28505240
TI  - Incidence of Gonorrhea and Chlamydia Following Human Immunodeficiency Virus
      Preexposure Prophylaxis Among Men Who Have Sex With Men: A Modeling Study.
AB  - Background: Preexposure prophylaxis (PrEP) is highly effective for preventing
      human immunodeficiency virus (HIV) infection, but risk compensation (RC) in men
      who have sex with men (MSM) raises concerns about increased sexually transmitted
      infections (STIs). The Center for Disease Control and Prevention's (CDC's) PrEP
      guidelines recommend biannual STI screening, which may reduce incidence by
      treating STIs that would otherwise remain undiagnosed. We investigated these two
      counteracting phenomena. Methods: With a network-based mathematical model of HIV,
      Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) transmission dynamics
      among MSM in the United States, we simulated PrEP uptake following the
      prescription indications and HIV/STI screening recommendations in the CDC
      guidelines. Scenarios varied PrEP coverage (the proportion of MSM indicated for
      PrEP who received it), RC (a reduction in the per-act probability of condom use),
      and the STI screening interval. Results: In our reference scenario (40% coverage,
      40% RC), 42% of NG and 40% of CT infections would be averted over the next
      decade. A doubling of RC would still result in net STI prevention relative to no
      PrEP. STIs declined because PrEP-related STI screening resulted in a 17% and 16%
      absolute increase in the treatment of asymptomatic and rectal STIs, respectively.
      Screening and timely treatment at quarterly vs biannual intervals would reduce
      STI incidence an additional 50%. Conclusions: Implementation of the CDC PrEP
      guidelines while scaling up PrEP coverage could result in a significant decline
      in STI incidence among MSM. Our study highlights the design of PrEP not only as
      antiretroviral medication but as combination HIV/STI prevention incorporating STI
      screening.

PMID- 28505242
TI  - RE: "RESPONSE AND FOLLOW-UP BIAS IN COHORT STUDIES".

PMID- 28505241
TI  - Tri-Ponderal Mass Index vs Body Mass Index in Estimating Body Fat During
      Adolescence.
AB  - Importance: Body mass index (BMI) is used to diagnose obesity in adolescents
      worldwide, despite evidence that weight does not scale with height squared in
      adolescents. To account for this, health care providers diagnose obesity using
      BMI percentiles for each age (BMI z scores), but this does not ensure that BMI is
      accurate in adolescents. Objective: To compare the accuracy of BMI vs other body
      fat indices of the form body mass divided by heightn in estimating body fat
      levels in adolescents. Design, Setting, and Participants: Cross-sectional data
      from the 1999 to 2006 US National Health and Nutrition Examination Survey were
      analyzed between September 2015 and December 2016. Main Outcomes and Measures:
      Dual-energy x-ray absorptiometry and anthropometric data were used to determine
      changes in body fat levels, body proportions, and the scaling relationships among
      body mass, height, and percent body fat. To assess the merits of each adiposity
      index, 3 criteria were used: stability with age, accuracy in estimating percent
      body fat, and accuracy in classifying adolescents as overweight vs normal weight.
      Results: Participants included 2285 non-Hispanic white participants aged 8 to 29
      years. Percent body fat varied with both age and height during adolescence,
      invalidating the standard weight-to-height regression as the way of finding the
      optimal body fat index. Because the correct regression model (percent body fat is
      proportional to mass divided by heightn) suggested that percent body fat scales
      to height with an exponent closer to 3, we therefore focused on the tri-ponderal
      mass index (TMI; mass divided by height cubed) as an alternative to BMI z scores.
      For ages 8 to 17 years, TMI yielded greater stability with age and estimated
      percent body fat better than BMI (R2 = 0.64 vs 0.38 in boys and R2 = 0.72 vs 0.66
      in girls). Moreover, TMI misclassified adolescents as overweight vs normal weight
      less often than BMI z scores (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 19.4%; 95% CI,
      17.8%-20.0%; P < .001) and performed equally as well as updated BMI percentiles
      derived from the same data set (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 8.0%; 95%
      CI, 6.9%-9.1%; P = .62). Conclusions and Relevance: The tri-ponderal mass index
      estimates body fat levels more accurately than BMI in non-Hispanic white
      adolescents aged 8 to 17 years. Moreover, TMI diagnoses adolescents as overweight
      more accurately than BMI z scores and equally as well as updated BMI percentiles
      but is much simpler to use than either because it does not involve complicated
      percentiles. Taken together, it is worth considering replacing BMI z scores with
      TMI to estimate body fat levels in adolescents.

PMID- 28505245
TI  - Atrial fibrillation: a left atrial neuro-myopathy?

PMID- 28505243
TI  - Association of Dual-Task Gait With Incident Dementia in Mild Cognitive
      Impairment: Results From the Gait and Brain Study.
AB  - Importance: Gait performance is affected by neurodegeneration in aging and has
      the potential to be used as a clinical marker for progression from mild cognitive
      impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive
      motor interface may predict dementia progression in older adults with MCI.
      Objective: To determine whether a dual-task gait test is associated with incident
      dementia in MCI. Design, Setting, and Participants: The Gait and Brain Study is
      an ongoing prospective cohort study of community-dwelling older adults that
      enrolled 112 older adults with MCI. Participants were followed up for 6 years,
      with biannual visits including neurologic, cognitive, and gait assessments. Data
      were collected from July 2007 to March 2016. Main Outcomes and Measures: Incident
      all-cause dementia was the main outcome measure, and single- and dual-task gait
      velocity and dual-task gait costs were the independent variables. A
      neuropsychological test battery was used to assess cognition. Gait velocity was
      recorded under single-task and 3 separate dual-task conditions using an
      electronic walkway. Dual-task gait cost was defined as the percentage change
      between single- and dual-task gait velocities: ([single-task gait velocity - dual
      task gait velocity]/ single-task gait velocity) * 100. Cox proportional hazard
      models were used to estimate the association between risk of progression to
      dementia and the independent variables, adjusted for age, sex, education,
      comorbidities, and cognition. Results: Among 112 study participants with MCI,
      mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to
      dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow
      single-task gait velocity (<0.8 m/second) was not associated with progression to
      dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual
      task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003)
      and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with
      dementia progression (incidence rate, 155 per 1000 person-years). The models
      remained robust after adjusting by baseline cognition except for dual-task gait
      cost when dichotomized. Conclusions and Relevance: Dual-task gait is associated
      with progression to dementia in patients with MCI. Dual-task gait testing is easy
      to administer and may be used by clinicians to decide further biomarker testing,
      preventive strategies, and follow-up planning in patients with MCI. Trial
      Registration: clinicaltrials.gov: NCT03020381.

PMID- 28505244
TI  - The Influence of Maternally Derived Antibody and Infant Age at Vaccination on
      Infant Vaccine Responses : An Individual Participant Meta-analysis.
AB  - Importance: The design of infant immunization schedules requires an understanding
      of the factors that determine the immune response to each vaccine antigen. Data
      Sources: Deidentified individual participant data from GlaxoSmithKline clinical
      trials were obtained through Clinical Study Data Request. The data were requested
      on January 2, 2015, and final data were received on April 11, 2016. Study
      Selection: Immunogenicity trials of licensed or unlicensed vaccines administered
      to infants were included if antibody concentrations in infants were measured
      prior to the first dose of vaccine. Data Extraction and Synthesis: The database
      was examined; studies that appeared to have appropriate data were reviewed. Main
      Outcomes and Measures: Antigen-specific antibody concentration measured 1 month
      after priming vaccine doses, before booster vaccination, and 1 month after
      booster vaccine doses. Results: A total of 7630 infants from 32 studies in 17
      countries were included. Mean (SD) age at baseline was 9.0 (2.3) weeks; 3906
      (51.2%) were boys. Preexisting maternal antibody inhibited infant antibody
      responses to priming doses for 20 of 21 antigens. The largest effects were
      observed for inactivated polio vaccine, where 2-fold higher maternal antibody
      concentrations resulted in 20% to 28% lower postvaccination antibody
      concentration (geometric mean ratios [GMRs], type 1: 0.80; 95% CI, 0.78-0.83;
      type 2: 0.72; 95% CI, 0.69-0.74; type 3: 0.78; 95% CI, 0.75-0.82). For acellular
      pertussis antigens, 2-fold higher maternal antibody was associated with 11% lower
      postvaccination antibody for pertussis toxoid (GMR, 0.89; 95% CI, 0.87-0.90) and
      filamentous hemagglutinin (GMR, 0.89; 95% CI, 0.88-0.90) and 22% lower pertactin
      antibody (GMR, 0.78; 95% CI, 0.77-0.80). For tetanus and diphtheria, these
      estimates were 13% (GMR, 0.87; 95% CI, 0.86-0.88) and 24% (GMR, 0.76; 95% CI,
      0.74-0.77), respectively. The influence of maternal antibody was still evident in
      reduced responses to booster doses of acellular pertussis, inactivated polio, and
      diphtheria vaccines at 12 to 24 months of age. Children who were older when first
      immunized had higher antibody responses to priming doses for 18 of 21 antigens,
      after adjusting for the effect of maternal antibody concentrations. The largest
      effect was seen for polyribosylribitol phosphate antibody, where responses were
      71% higher per month (GMR, 1.71; 95% CI, 1.52-1.92). Conclusions and Relevance:
      Maternal antibody concentrations and infant age at first vaccination both
      influence infant vaccine responses. These effects are seen for almost all
      vaccines contained in global immunization programs and influence immune response
      for some vaccines even at the age of 24 months. These data highlight the
      potential for maternal immunization strategies to influence established infant
      programs.

PMID- 28505246
TI  - Effects of long-term exogenous testosterone administration on ovarian morphology,
      determined by transvaginal (3D) ultrasound in female-to-male transsexuals.
AB  - STUDY QUESTION: Does long-term exogenous testosterone administration result in
      polycystic ovarian morphology (PCOM), determined by (3D) transvaginal ultrasound
      (TVU) in female-to-male transsexuals (FtMs). SUMMARY ANSWER: Long-term exogenous
      testosterone administration in FtMs does not result in PCOM determined by (3D)
      TVU. WHAT IS KNOWN ALREADY: The role of androgens in the pathophysiology of
      polycystic ovary syndrome (PCOS) is still unclear. From animal studies, intra
      ovarian androgens have been suggested to disturb folliculogenesis, through a pro
      atretic effect on growing follicles. It remains debatable whether exogenous
      androgens induce PCOM in humans. In the past histomorphologic studies indicated
      that androgen administration in FtMs could cause PCO-like changes. However,
      ultrasound morphology is an established criterion for PCOS, TVU data of ovaries
      after prolonged androgen exposure are lacking. STUDY DESIGN, SIZE, DURATION:
      Prospective, observational, case-control study, in an academic setting, performed
      in 2014-2015, including 56 FtMs and 80 controls. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The study population consisted of adult FtMs treated with long-term
      testosterone, as part of their cross-sex hormone treatment, and scheduled for sex
      reassignment surgery (bilateral salpingo-oophorectomy). Prior to the operation,
      under anaesthetics TVU measurements (3D transvaginal probe 3-9 MHz; HD11, Philips
      Ultrasound, Inc.) of the ovaries were performed. The control group consisted of
      females from a general population who underwent the same TVU and analysis. Antral
      follicle count (AFC) (3D) and ovarian volume (3D) were calculated using
      specialized software. PCOM was defined as AFC of 12 or more follicles (2-10 mm)
      in at least one ovary. MAIN RESULTS AND THE ROLE OF CHANCE: Prevalence rates of
      PCOM were not significantly different in the FtMs compared to controls,
      determined by (3D) TVU: 32.1% (17/53) versus 30.7% (23/75), P = 0.87.
      LIMITATIONS, REASONS FOR CAUTION: Testosterone levels in FtMs are
      supraphysiological, and may not be comparable to the testosterone levels in women
      with PCOS. However, we applied a unique and ethically acceptable opportunity of
      exploring the effects of androgens on human ovaries. WIDER IMPLICATIONS OF THE
      FINDINGS: This first explorative study shows that long-term exogenous
      testosterone administration in adult women does not seem to induce PCOM
      determined by TVU. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION
      NUMBER: The trial was registered at the Dutch Trial Register
      (www.trialregister.nl), registration number NTR4784.

PMID- 28505247
TI  - Single-cell regulome data analysis by SCRAT.
AB  - Summary: Emerging single-cell technologies (e.g. single-cell ATAC-seq, DNase-seq
      or ChIP-seq) have made it possible to assay regulome of individual cells. Single
      cell regulome data are highly sparse and discrete. Analyzing such data is
      challenging. User-friendly software tools are still lacking. We present SCRAT, a
      Single-Cell Regulome Analysis Toolbox with a graphical user interface, for
      studying cell heterogeneity using single-cell regulome data. SCRAT can be used to
      conveniently summarize regulatory activities according to different features
      (e.g. gene sets, transcription factor binding motif sites, etc.). Using these
      features, users can identify cell subpopulations in a heterogeneous biological
      sample, infer cell identities of each subpopulation, and discover distinguishing
      features such as gene sets and transcription factors that show different
      activities among subpopulations. Availability and implementation: SCRAT is freely
      available at https://zhiji.shinyapps.io/scrat as an online web service and at
      https://github.com/zji90/SCRAT as an R package. Contact: hji@jhu.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28505248
TI  - Lactobacilli-lactoferrin interplay in Chlamydia trachomatis infection.
AB  - In the cervicovaginal microenvironment, lactobacilli are known to protect against
      genital infections and, amongst the host defence compounds, lactoferrin has
      recently acquired importance for its anti-microbial and anti-inflammatory
      properties. An abnormal genital microenvironment facilitates the acquisition of
      pathogens like Chlamydia trachomatis, the leading cause of bacterial sexually
      transmitted infections worldwide. The aim of our study is to investigate the
      effects of Lactobacillus crispatus, Lactobacillus brevis and bovine lactoferrin
      on chlamydial infection, in order to shed light on the complex interplay between
      host defence mechanisms and C. trachomatis. We have also evaluated the effect of
      these defence factors to modulate the chlamydia-mediated inflammatory state. To
      this purpose, we have determined the infectivity and progeny production of C.
      trachomatis as well as interleukin-8 and interleukin-6 synthesis. The main result
      of our study is that the combination of L. brevis and bovine lactoferrin is the
      most effective in inhibiting the early phases (adhesion and invasion) of C.
      trachomatis infection of cervical epithelial cells and in decreasing the levels
      of both cytokines. In conclusion, the interaction between L. brevis and
      lactoferrin seems to play a role in the protection against C. trachomatis,
      reducing the infection and regulating the immunomodulatory activity, thus
      decreasing the risk of severe complications.

PMID- 28505250
TI  - Treating the Symptom but Not the Underlying Disease in Infective Endocarditis: A
      Teachable Moment.

PMID- 28505251
TI  - False discovery rate control incorporating phylogenetic tree increases detection
      power in microbiome-wide multiple testing.
AB  - Motivation: Next generation sequencing technologies have enabled the study of the
      human microbiome through direct sequencing of microbial DNA, resulting in an
      enormous amount of microbiome sequencing data. One unique characteristic of
      microbiome data is the phylogenetic tree that relates all the bacterial species.
      Closely related bacterial species have a tendency to exhibit a similar
      relationship with the environment or disease. Thus, incorporating the
      phylogenetic tree information can potentially improve the detection power for
      microbiome-wide association studies, where hundreds or thousands of tests are
      conducted simultaneously to identify bacterial species associated with a
      phenotype of interest. Despite much progress in multiple testing procedures such
      as false discovery rate (FDR) control, methods that take into account the
      phylogenetic tree are largely limited. Results: We propose a new FDR control
      procedure that incorporates the prior structure information and apply it to
      microbiome data. The proposed procedure is based on a hierarchical model, where a
      structure-based prior distribution is designed to utilize the phylogenetic tree.
      By borrowing information from neighboring bacterial species, we are able to
      improve the statistical power of detecting associated bacterial species while
      controlling the FDR at desired levels. When the phylogenetic tree is mis
      specified or non-informative, our procedure achieves a similar power as
      traditional procedures that do not take into account the tree structure. We
      demonstrate the performance of our method through extensive simulations and real
      microbiome datasets. We identified far more alcohol-drinking associated bacterial
      species than traditional methods. Availability and implementation: R package
      StructFDR is available from CRAN. Contact: chen.jun2@mayo.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28505252
TI  - Financing and Distribution of Pharmaceuticals in the United States.

PMID- 28505249
TI  - Sialic acid deficiency is associated with oxidative stress leading to muscle
      atrophy and weakness in GNE myopathy.
AB  - Sialic acids are monosaccharides found in terminal sugar chains of cell surfaces
      and proteins; they have various biological functions and have been implicated in
      health and disease. Genetic defects of the GNE gene which encodes a critical
      bifunctional enzyme for sialic acid biosynthesis, lead to GNE myopathy, a disease
      manifesting with progressive muscle atrophy and weakness. The likely mechanism of
      disease is a lack of sialic acids. There remains, however, an unexplained link
      between hyposialylation and the muscle atrophy and weakness. In this study, we
      found that muscle proteins were highly modified by S-nitrosylation, and that
      oxidative stress-responsive genes were significantly upregulated, in
      hyposialylated muscles from human GNE myopathy patients and model mice. In both
      in vitro and in vivo models, the production of reactive oxygen species (ROS) was
      elevated with cellular hyposialylation, and increasing overall sialylation by
      extrinsic sialic acid intake reduced ROS and protein S-nitrosylation. More
      importantly, the antioxidant, oral N-acetylcysteine led to amelioration of the
      muscle atrophy and weakness in Gne mutant mice. Our data provide evidence of
      additional important function of sialic acids as a ROS scavenger in skeletal
      muscles, expanding our understanding on how sialic acid deficiency contributes to
      disease pathology, and identify oxidative stress as a therapeutic target in GNE
      myopathy.

PMID- 28505253
TI  - Pulmonary venoplasty with a pericardial conduit in living-donor lobar lung
      retransplantation.
AB  - In living-donor lobar lung transplantation, donor lobectomies must be performed
      carefully for both donors and recipients. Furthermore, the recipients undergo
      pneumonectomies rather than lobectomies. Occasionally, anastomosis of the
      pulmonary vessels is difficult in living-donor lobar lung transplantation because
      of the limited length of the pulmonary vessels in the graft. This report
      describes a successful case of pulmonary venoplasty using an autologous
      pericardial conduit, which was interposed between the superior pulmonary vein of
      the recipient and the inferior pulmonary vein of the donor in living-donor lobar
      lung retransplantation. This technique may be required for the success of living
      donor lobar lung retransplantation.

PMID- 28505254
TI  - Building a Broader Consensus for Health Reform.

PMID- 28505255
TI  - Editorial: The many facets of Escherichia coli: from beneficial bug and genetic
      workhorse to dangerous menace for plant and creature.

PMID- 28505256
TI  - CRISPR/Cas system for yeast genome engineering: advances and applications.
AB  - The methods based on the clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated (Cas) system have quickly gained popularity
      for genome editing and transcriptional regulation in many organisms, including
      yeast. This review aims to provide a comprehensive overview of CRISPR application
      for different yeast species: from basic principles and genetic design to
      applications.

PMID- 28505258
TI  - Modelling and mathematical analysis of the M$_{2}$ receptor-dependent joint
      signalling and secondary messenger network in CHO cells.
AB  - The muscarinic M$_{2}$ receptor is a prominent member of the GPCR family and
      strongly involved in heart diseases. Recently published experimental work
      explored the cellular response to iperoxo-induced M$_{2}$ receptor stimulation in
      Chinese hamster ovary (CHO) cells. To better understand these responses, we
      modelled and analysed the muscarinic M$_{2}$ receptor-dependent signalling
      pathway combined with relevant secondary messenger molecules using mass action.
      In our literature-based joint signalling and secondary messenger model, all
      binding and phosphorylation events are explicitly taken into account in order to
      enable subsequent stoichiometric matrix analysis. We propose constraint flux
      sampling (CFS) as a method to characterize the expected shift of the steady state
      reaction flux distribution due to the known amount of cAMP production and PDE4
      activation. CFS correctly predicts an experimentally observable influence on the
      cytoskeleton structure (marked by actin and tubulin) and in consequence a change
      of the optical density of cells. In a second step, we use CFS to simulate the
      effect of knock-out experiments within our biological system, and thus to rank
      the influence of individual molecules on the observed change of the optical cell
      density. In particular, we confirm the relevance of the protein RGS14, which is
      supported by current literature. A combination of CFS with Elementary Flux Mode
      analysis enabled us to determine the possible underlying mechanism. Our analysis
      suggests that mathematical tools developed for metabolic network analysis can
      also be applied to mixed secondary messenger and signalling models. This could be
      very helpful to perform model checking with little effort and to generate
      hypotheses for further research if parameters are not known.

PMID- 28505259
TI  - Immune oncology and neuroendocrine tumors.

PMID- 28505257
TI  - MicroRNAs in dysfunctional adipose tissue: cardiovascular implications.
AB  - In this review, we focus on the emerging role of microRNAs, non-coding RNAs that
      regulate gene expression and signaling pathways, in dysfunctional adipose tissue.
      We highlight current paradigms of microRNAs involved in adipose differentiation
      and function in depots such as white, brown, and beige adipose tissues and
      potential implications of microRNA dysregulation in human disease such as
      obesity, inflammation, microvasculature dysfunction, and related cardiovascular
      diseases. We highlight accumulating studies indicating that adipocyte-derived
      microRNAs may not only serve as biomarkers of cardiometabolic disease, but also
      may directly regulate gene expression of other tissues. Finally, we discuss the
      future prospects, challenges, and emerging strategies for microRNA delivery and
      targeting for therapeutic applications in cardiovascular disease states
      associated with adipocyte dysfunction.

PMID- 28505260
TI  - Evolution of Two Short Interspersed Elements in Callorhinchus milii
      (Chondrichthyes, Holocephali) and Related Elements in Sharks and the Coelacanth.
AB  - Short interspersed elements (SINEs) are non-autonomous retrotransposons. Although
      they usually show fast evolutionary rates, in some instances highly conserved
      domains (HCDs) have been observed in elements with otherwise divergent sequences
      and from distantly related species. Here, we document the life history of two HCD
      SINE families in the elephant shark Callorhinchus milii, one specific to the
      holocephalan lineage (CmiSINEs) and another one (SacSINE1-CM) with homologous
      elements in sharks and the coelacanth (SacSINE1s, LmeSINE1s). The analyses of
      their relationships indicated that these elements share the same 3'-tail, which
      would have allowed both elements to rise to high copy number by exploiting the C.
      milii L2-2_CM long interspersed element (LINE) enzymes. Molecular clock analysis
      on SINE activity in C. milii genome evidenced two replication bursts occurring
      right after two major events in the holocephalan evolution: the end-Permian mass
      extinction and the radiation of modern Holocephali. Accordingly, the same
      analysis on the coelacanth homologous elements, LmeSINE1, identified a
      replication wave close to the split age of the two extant Latimeria species. The
      genomic distribution of the studied SINEs pointed out contrasting results: some
      elements were preferentially sorted out from gene regions, but accumulated in
      flanking regions, while others appear more conserved within genes. Moreover, data
      from the C. milii transcriptome suggest that these SINEs could be involved in
      miRNA biogenesis and may be targets for miRNA-based regulation.

PMID- 28505262
TI  - The Basal Ganglia Striosomes Affect the Modulation of Conflicts by Subliminal
      Information-Evidence from X-Linked Dystonia Parkinsonism.
AB  - Cognitive control is relevant when distracting information induces behavioral
      conflicts. Such conflicts can be produced consciously and by subliminally
      processed information. Interestingly, both sources of conflict interact
      suggesting that they share neural mechanisms. Here, we ask whether conjoint
      effects between different sources of conflict are modulated by microstructural
      basal ganglia dysfunction. To this end, we carried out an electroencephalography
      study and examined event-related potentials (ERPs) including source localization
      using a combined flanker-subliminal priming task in patients with X-linked
      dystonia Parkinsonism (XDP) and a group of healthy controls. XDP in its early
      stages is known to predominantly affect the basal ganglia striosomes. The results
      suggest that conjoint effects between subliminal and conscious sources of
      conflicts are modulated by the striosomes and were stronger in XDP patients. The
      neurophysiological data indicate that this effect is related to modulations in
      conflict monitoring and response selection (N2 ERP) mechanisms engaging the
      anterior cingulate cortex. Bottom-up perceptual gating, attentional selection,
      and motor response activation processes in response to the stimuli (P1, N1, and
      lateralized readiness potential ERPs) were unaffected. Taken together, these data
      indicate that striosomes modulate the processing of conscious and subliminal
      sources of conflict suggesting that microstructural basal ganglia properties are
      relevant for cognitive control.

PMID- 28505261
TI  - Survival and Causes of Death Among People With Clinically Diagnosed
      Synucleinopathies With Parkinsonism: A Population-Based Study.
AB  - Importance: To our knowledge, a comprehensive study of the survival and causes of
      death of persons with synucleinopathies compared with the general population has
      not been conducted. Understanding the long-term outcomes of these conditions may
      inform patients and caregivers of the expected disease duration and may help with
      care planning. Objective: To compare survival rates and causes of death among
      patients with incident, clinically diagnosed synucleinopathies and age- and sex
      matched referent participants. Design, Setting, and Participants: This population
      based study used the Rochester Epidemiology Project medical records-linkage
      system to identify all residents in Olmsted County, Minnesota, who received a
      diagnostic code of parkinsonism from 1991 through 2010. A movement-disorders
      specialist reviewed the medical records of each individual to confirm the
      presence of parkinsonism and determine the type of synucleinopathy. For each
      confirmed patient, an age- and sex-matched Olmsted County resident without
      parkinsonism was also identified. Main Outcomes and Measures: We determined the
      age- and sex-adjusted risk of death for each type of synucleinopathy, the median
      time from diagnosis to death, and the causes of death. Results: Of the 461
      patients with synucleinopathies, 279 (60.5%) were men, and of the 452 referent
      participants, 272 (60.2%) were men. From 1991 through 2010, 461 individuals
      received a diagnosis of a synucleinopathy (309 [67%] of Parkinson disease, 81
      [17.6%] of dementia with Lewy bodies, 55 [11.9%] of Parkinson disease dementia,
      and 16 [3.5%] of multiple system atrophy with parkinsonism). During follow-up,
      68.6% (n = 316) of the patients with synucleinopathies and 48.7% (n = 220) of the
      referent participants died. Patients with any synucleinopathy died a median of 2
      years earlier than referent participants. Patients with multiple system atrophy
      with parkinsonism (hazard ratio, 10.51; 95% CI, 2.92-37.82) had the highest risk
      of death compared with referent participants, followed by those with dementia
      with Lewy bodies (hazard ratio, 3.94; 95% CI, 2.61-5.94), Parkinson disease with
      dementia (hazard ratio, 3.86; 95% CI, 2.36-6.30), and Parkinson disease (hazard
      ratio, 1.75; 95% CI, 1.39-2.21). Neurodegenerative disease was the most frequent
      cause of death listed on the death certificate for patients, and cardiovascular
      disease was the most frequent cause of death among referent participants.
      Conclusions and Relevance: Individuals with multiple system atrophy with
      parkinsonism, dementia with Lewy bodies, and Parkinson disease dementia have
      increased mortality compared with the general population. The mortality among
      persons with Parkinson disease is only moderately increased compared with the
      general population.

PMID- 28505263
TI  - Substantial Impairment of Voriconazole Clearance by High-Dose Meropenem in a
      Patient With Renal Failure.
AB  - A critically ill patient with multiple postoperative infections repeatedly
      required profound voriconazole dose reductions whenever high-dose meropenem was
      added. Subsequent in vitro assessment confirmed inhibition of cytochrome P450
      (CYP) 2C19 and CYP3A4 by meropenem, suggesting that during meropenem treatment,
      narrow therapeutic index drugs metabolized by these CYPs require close
      monitoring.

PMID- 28505264
TI  - Geographical Information Systems in Determination of Cutaneous Leishmaniasis
      Spatial Risk Level Based on Distribution of Vector Species in Imamoglu Province,
      Adana.
AB  - The Imamoglu district located in the southeast of Adana province in Turkey is an
      endemic focus of cutaneous leishmaniasis (CL) owing to dominancy of Phlebotomus
      tobbi, which is a probable vector of Leishmania infantum. About 11.26% of CL
      cases reported each year are from Imamoglu, Adana, and between 2008 and 2015, 223
      cases of CL were reported. Leishmania infantum, which may be transmitted by P.
      tobbi, Phlebotomus neglectus/syriacus, and Phlebotomus perfiliewi, is referred as
      leishmaniasis factor in Adana. Thus, the aim of this study was to map the risk
      areas for each sand fly species using remote sensing images based on
      environmental factors and geographical characteristics. Two field works in two
      consecutive years (2013 and 2014) were conducted and six sand fly species were
      caught, four of which were identified as probable vector species. Field work
      results were compared with environmental data obtained from satellite images by
      univariate and binary logistic regression in PASW. ARCMAP 10.2 software was used
      for geographical adjustments, creating a database and estimating a risk model by
      using previous risk value formulas. The results showed that the distribution of
      three probable leishmaniasis vectors (P. tobbi, P. neglectus/syriacus, and P.
      perfiliewi) was associated with normalized difference vegetation index (NDVI),
      digital elevation model (DEM), night-time land surface temperature (LSTNIGHT),
      and emissivity (EMIS31) values, which were related to the local authorities, who
      take these findings into account when deciding on high risk areas for CL.

PMID- 28505267
TI  - Integrating Models of Neurologic and Psychiatric Disease.

PMID- 28505266
TI  - Guidance for Modifying the Definition of Diseases: A Checklist.
AB  - Importance: No guidelines exist currently for guideline panels and others
      considering changes to disease definitions. Panels frequently widen disease
      definitions, increasing the proportion of the population labeled as unwell and
      potentially causing harm to patients. We set out to develop a checklist of
      issues, with guidance, for panels to consider prior to modifying a disease
      definition. Observations: We assembled a multidisciplinary, multicontinent
      working group of 13 members, including members from the Guidelines International
      Network, Grading of Recommendations Assessment, Development and Evaluation
      working group, and the World Health Organisation. We used a 5-step process to
      develop the checklist: (1) a literature review of issues, (2) a draft outline
      document, (3) a Delphi process of feedback on the list of issues, (4) a 1-day
      face-to-face meeting, and (5) further refinement of the checklist. The literature
      review identified 12 potential issues. From these, the group developed an 8-item
      checklist that consisted of definition changes, number of people affected,
      trigger, prognostic ability, disease definition precision and accuracy, potential
      benefits, potential harms, and the balance between potential harms and benefits.
      The checklist is accompanied by an explanation of each item and the types of
      evidence to assess each one. We used a panel's recent consideration of a proposed
      change in the definition of gestational diabetes mellitus (GDM) to illustrate use
      of the checklist. Conclusions and Relevance: We propose that the checklist be
      piloted and validated by groups developing new guidelines. We anticipate that the
      use of the checklist will be a first step to guidance and better documentation of
      definition changes prior to introducing modified disease definitions.

PMID- 28505265
TI  - The Influence of the Topography of the Ailao Mountains on Congregated Landings of
      Airborne Sogatella furcifera (Hemiptera: Delphacidae) Populations.
AB  - The Sogatella furcifera (Horvath) is an important migrating rice pest whose
      outbreak may be caused by large-scale congregated landings. Hitherto, the
      meteorological factors that influence congregated landings were thought to be
      rainfall and downdraft. However, for migratory insects on a plateau, low
      temperature may be another key factor leading to congregated landings. However,
      no reports have been published. Therefore, this paper evaluates the reason for a
      large-scale congregated landing in the mountainous area in Yuanjiang via light
      trap monitoring. The meteorological backgrounds during light catch peaks were
      analyzed using the numeric simulation method. The results were as follows: 1)
      from May 7th to May 9th, 2012, the congregated landing of S. furcifera was caused
      by precipitation; 2) the congregated landing of S. furcifera on May 10th, 2012,
      was a result of low temperatures in the mountainous region. The driving airflow
      of S. furcifera climbed along the mountain terrain, which led to a decrease in
      temperature with the rise of the mountain terrain. Low temperature created
      physiological changes in S. furcifera, forcing S. furcifera to a lower flight
      altitude and eventually to a congregated landing; and 3) in the statistical
      analysis on 39 peak periods from 2010 to 2016 in the early spring, 20 peaks were
      caused by precipitation, and 19 peaks were caused by a low temperature barrier.
      Therefore, this study provided evidence of a plateau-migrating S. furcifera
      population congregated landing caused by low temperature.

PMID- 28505268
TI  - Pharmacodynamics of dose-escalated 'front-loading' polymyxin B regimens against
      polymyxin-resistant mcr-1-harbouring Escherichia coli.
AB  - Objectives: Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to
      the 'last-line' polymyxins and have been reported worldwide. Our objective was to
      define the impact of increasing the initial polymyxin B dose intensity against an
      mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin
      resistance on the dynamics of bacterial killing and resistance. Methods: A hollow
      fibre infection model (HFIM) was used to simulate polymyxin B regimens against an
      mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days. Four escalating
      polymyxin B 'front-loading' regimens (3.33, 6.66, 13.3 or 26.6 mg/kg for one dose
      followed by 1.43 mg/kg every 12 h starting 12 h later) simulating human
      pharmacokinetics were utilized in the HFIM. A mechanism-based, mathematical model
      was developed using S-ADAPT to characterize bacterial killing. Results: The 3.33
      mg/kg 'front-loading' regimen resulted in regrowth mirroring the growth control.
      The 6.66, 13.3 and 26.6 mg/kg 'front-loading' regimens resulted in maximal
      bacterial reductions of 1.91, 3.79 and 6.14 log 10 cfu/mL, respectively.
      Irrespective of the early polymyxin B exposure (24 h AUC), population analysis
      profiles showed similar growth of polymyxin B-resistant subpopulations. The HFIM
      data were well described by the mechanism-based model integrating three
      subpopulations (susceptible, intermediate and resistant). Compared with the
      susceptible subpopulation of mcr-1 -harbouring E. coli , the resistant
      subpopulation had an approximately 10-fold lower rate of killing due to polymyxin
      B treatment. Conclusions: Manipulating initial dose intensity of polymyxin B was
      not able to overcome plasmid-mediated resistance due to mcr-1 in E. coli . This
      reinforces the need to develop new combinatorial strategies to combat these
      highly resistant Gram-negative bacteria.

PMID- 28505269
TI  - New mutations in non-syndromic primary ovarian insufficiency patients identified
      via whole-exome sequencing.
AB  - STUDY QUESTION: Is it possible to identify new mutations potentially associated
      with non-syndromic primary ovarian insufficiency (POI) via whole-exome sequencing
      (WES)? SUMMARY ANSWER: WES is an efficient tool to study genetic causes of POI as
      we have identified new mutations, some of which lead to protein destablization
      potentially contributing to the disease etiology. WHAT IS KNOWN ALREADY: POI is a
      frequently occurring complex pathology leading to infertility. Mutations in only
      few candidate genes, mainly identified by Sanger sequencing, have been
      definitively related to the pathogenesis of the disease. STUDY DESIGN, SIZE,
      DURATION: This is a retrospective cohort study performed on 69 women affected by
      POI. PARTICIPANTS/MATERIALS, SETTING, METHODS: WES and an innovative
      bioinformatics analysis were used on non-synonymous sequence variants in a subset
      of 420 selected POI candidate genes. Mutations in BMPR1B and GREM1 were modeled
      by using fragment molecular orbital analysis. MAIN RESULTS AND THE ROLE OF
      CHANCE: Fifty-five coding variants in 49 genes potentially related to POI were
      identified in 33 out of 69 patients (48%). These genes participate in key
      biological processes in the ovary, such as meiosis, follicular development,
      granulosa cell differentiation/proliferation and ovulation. The presence of at
      least two mutations in distinct genes in 42% of the patients argued in favor of a
      polygenic nature of POI. LIMITATIONS, REASONS FOR CAUTION: It is possible that
      regulatory regions, not analyzed in the present study, carry further variants
      related to POI. WIDER IMPLICATIONS OF THE FINDINGS: WES and the in silico
      analyses presented here represent an efficient approach for mapping variants
      associated with POI etiology. Sequence variants presented here represents
      potential future genetic biomarkers. STUDY FUNDING/COMPETING INTEREST(S): This
      study was supported by the Universidad del Rosario and Colciencias (Grants
      CS/CIGGUR-ABN062-2016 and 672-2014). Colciencias supported Liliana Catherine
      Patino's work (Fellowship: 617, 2013). The authors declare no conflict of
      interest.

PMID- 28505270
TI  - HTSvis: a web app for exploratory data analysis and visualization of arrayed high
      throughput screens.
AB  - Summary: Arrayed high-throughput screens (HTS) cover a broad range of
      applications using RNAi or small molecules as perturbations and specialized
      software packages for statistical analysis have become available. However,
      exploratory data analysis and integration of screening results has remained
      challenging due to the size of the data sets and the lack of user-friendly tools
      for interpretation and visualization of screening results. Here we present
      HTSvis, a web application to interactively visualize raw data, perform quality
      control and assess screening results from single to multi-channel measurements
      such as image-based screens. Per well aggregated raw and analyzed data of various
      assay types and scales can be loaded in a generic tabular format. Availability
      and implementation: HTSvis is distributed as an open-source R package,
      downloadable from https://github.com/boutroslab/HTSvis and can also be accessed
      at http://htsvis.dkfz.de . Contact: m.boutros@dkfz.de. Supplementary information:
      Supplementary data are available at Bioinformatics online .

PMID- 28505271
TI  - Development and psychometric evaluation of a Persian version of the Death
      Depression Scale-Revised: a cross-cultural adaptation for patients with advanced
      cancer.
AB  - Objective: The surfacing of thoughts and depressive affect associated with the
      prospect of death are prevalent among patients with advanced cancer. Because
      death cognitions and associated negative affect occur along an adaptive-less
      adaptive continuum, it is essential that valid and reliable instruments are
      available to measure death depression. The present study aimed to determine the
      psychometric properties of the Death Depression Scale among Iranian patients with
      advanced cancer. Methods: About 497 cancer patients completed a Persian version
      of the 21-item Death Depression Scale-Revised. The face, content and construct
      validity of the scale were ascertained. Reliability was also assessed using
      internal consistency, construct reliability and intra-class correlation
      coefficient (ICC). Results: Construct validity determined one factor with an
      eigenvalue greater than 1. The model had a good fit (chi2 (179, N = 248) =
      520.345, P < 0.001; chi2/df = 2.907, CFI = 0.916, TLI = 0.902, IFI = 0.917, SRMR
      = 0.049 and RMSEA = 0.088 (90% confidence interval = 0.079-0.097)) with all
      factors loadings greater than 0.5 and statistically significant. The internal
      consistency, construct reliability and ICC were greater than 0.70. Convergent
      validity of the scale was demonstrated. Conclusions: Findings revealed that the
      Persian version of the Death Depression Scale-Revised is valid and reliable, and
      may be used to assess and evaluate death depression in Iranian patients with
      advanced cancer.

PMID- 28505272
TI  - T-tubule remodelling disturbs localized beta2-adrenergic signalling in rat
      ventricular myocytes during the progression of heart failure.
AB  - Aims: Cardiomyocyte beta2-adrenergic receptor (beta2AR) cyclic adenosine
      monophosphate (cAMP) signalling is regulated by the receptors' subcellular
      location within transverse tubules (T-tubules), via interaction with structural
      and regulatory proteins, which form a signalosome. In chronic heart failure (HF),
      beta2ARs redistribute from T-tubules to the cell surface, which disrupts
      functional signalosomes and leads to diffuse cAMP signalling. However, the
      functional consequences of structural changes upon beta2AR-cAMP signalling during
      progression from hypertrophy to advanced HF are unknown. Methods and results: Rat
      left ventricular myocytes were isolated at 4-, 8-, and 16-week post-myocardial
      infarction (MI), beta2ARs were stimulated either via whole-cell perfusion or
      locally through the nanopipette of the scanning ion conductance microscope. cAMP
      release was measured via a Forster Resonance Energy Transfer-based sensor Epac2
      camps. Confocal imaging of di-8-ANNEPS-stained cells and immunoblotting were used
      to determine structural alterations. At 4-week post-MI, T-tubule regularity,
      density and junctophilin-2 (JPH2) expression were significantly decreased. The
      amplitude of local beta2AR-mediated cAMP in T-tubules was reduced and cAMP
      diffused throughout the cytosol instead of being locally confined. This was
      accompanied by partial caveolin-3 (Cav-3) dissociation from the membrane. At 8
      week post-MI, the beta2AR-mediated cAMP response was observed at the T-tubules
      and the sarcolemma (crest). Finally, at 16-week post-MI, the whole cell beta2AR
      mediated cAMP signal was depressed due to adenylate cyclase dysfunction, while
      overall Cav-3 levels were significantly increased and a substantial portion of
      Cav-3 dissociated into the cytosol. Overexpression of JPH2 in failing cells in
      vitro or AAV9.SERCA2a gene therapy in vivo did not improve beta2AR-mediated
      signal compartmentation or reduce cAMP diffusion. Conclusion: Although changes in
      T-tubule structure and beta2AR-mediated cAMP signalling are significant even at 4
      week post-MI, progression to the HF phenotype is not linear. At 8-week post-MI
      the loss of beta2AR-mediated cAMP is temporarily reversed. Complete
      disorganization of beta2AR-mediated cAMP signalling due to changes in functional
      receptor localization and cellular structure occurs at 16-week post-MI.

PMID- 28505273
TI  - Factor Analysis of an Expanded Halstead-Reitan Battery and the Structure of
      Neurocognition.
AB  - Objective: The structure of neurocognition is explored by examining the
      neurocognitive domains underlying comprehensive neuropsychological assessment of
      cognitively healthy individuals. Method: Exploratory factor analysis was
      conducted on the adult normative dataset of an expanded Halstead-Reitan Battery
      (eHRB), comprising Caucasian and African American participants. The factor
      structure contributions of the original HRB, eHRB expansion, and Wechsler
      intelligence scales were compared. Demographic effects were examined on composite
      factor scores calculated using confirmatory factor analysis. Results: The full
      eHRB had an eight-factor structure, with latent constructs including: 'working
      memory', 'fluency', 'verbal episodic memory', 'visuospatial cognition'
      (visuospatial memory and problem solving), 'perceptual-motor speed' (speed for
      processing visual/tactile material and hand-motor execution), 'perceptual
      attention' (attention to sensory-perceptual information), 'semantic knowledge'
      (knowledge acquired through education and culturally-based experiences), and
      'phonological decoding' (grapheme-phoneme processing essential for sounding-out
      words). 'Perceptual-motor speed' and 'perceptual attention' were most negatively
      associated with age, whereas 'semantic knowledge' and 'phonological decoding'
      were most resistant to aging. 'Semantic knowledge' showed the greatest dependence
      on demographic background, including education and ethnicity. Gender differences
      in cognitive performances were negligible across all domains except 'phonological
      decoding' with women slightly outperforming men. The original HRB contributed
      four neurocognitive domains, the eHRB expansion three domains, and the Wechsler
      scales one additional domain but with restructuring of verbal factors.
      Conclusion: Eight neurocognitive domains underlie performance of healthy
      cognitive individuals during comprehensive neuropsychological assessment. These
      domains serve as framework for understanding the constructs measured by commonly
      used neuropsychological tests and may represent the structure of neurocognition.

PMID- 28505274
TI  - Migration Analysis of Sogatella furcifera (Hemiptera: Delphacidae) in the
      Northeastern Hunan Province in June.
AB  - The Sogatella furcifera (Horvath) is a notorious and destructive insect pest,
      targeting >4 million hectares of rice cultivated in the Hunan Province. To
      understand the immigration dynamics, we collected S. furcifera light trap catches
      from 2006 to 2012 at Niangxiang, Linxiang, and Hanshou. We conducted a migration
      analysis to estimate the immigration source for the northeastern Hunan Province
      in June. Moreover, we dissected the ovaries of S. furcifera to classify
      population characteristics. We found that the first appearance of S. furcifera
      occurred from late April to early May, with June as the primary time for
      migrations into the northeastern Hunan Province. The majority of June ovaries
      caught in light traps were Grade I and Grade II, whereas those collected in paddy
      fields were Grade III and Grade IV, suggesting that the majority of S. furcifera
      immigrated into the northeastern Hunan Province. Our analysis points toward the
      northern and central Indo China Peninsula, the southern Hunan Province, the
      Guangxi Zhuang Autonomous Region Province, the Guangdong Province, and the Hainan
      Province as possible immigration sources of S. furcifera in June for the
      northeastern Hunan Province. We propose terrain, loss of forward flow, and wind
      shear as causes for the difference observed in light trap catches between
      Ningxiang, Linxiang, and Hanshou monitoring stations in the June of 2009. Thus,
      our results suggest that monitoring and forecasting of S. furcifera should be
      done with particular emphasis in June.

PMID- 28505275
TI  - Maternal Stressors and Social Support and Risks of Delivering Babies With
      Gastroschisis or Hypospadias.
AB  - We examined the association of maternal stressful life events and social support
      with risks of gastroschisis and hypospadias, using data from the National Birth
      Defects Prevention Study, a population-based case-control study of US births
      taking place in 2006-2011. We examined maternal self-reports of 7 life events and
      3 sources of social support during the periconceptional period among mothers of
      593 gastroschisis cases, 1,142 male hypospadias cases, and 4,399 nonmalformed
      controls. Responses to the questions on stressful life events were summed to form
      an index (higher is worse), as were responses to questions on social support
      (higher is better). We used logistic regression to estimate adjusted odds ratios
      and 95% confidence intervals. The adjusted odds ratios for gastroschisis for a 4
      point increase in the stress index were 3.5 (95% confidence interval (CI): 2.6,
      4.8) among nonteenage mothers (age >=20 years) and 1.0 (95% CI: 0.5, 1.7) among
      teenage mothers (age <20 years). The odds ratio for hypospadias (among all
      mothers) was 0.8 (95% CI: 0.7, 1.1). Adjusted odds ratios for a social support
      score of 3 (versus 0) in the 3 respective groups were 0.6 (95% CI: 0.4, 1.0), 1.0
      (95% CI: 0.5, 2.3), and 0.6 (95% CI: 0.4, 0.9). Given the lack of prior research
      on these outcomes and stress, results should be interpreted with caution.

PMID- 28505276
TI  - African Tick Bite Fever Treated Successfully With Rifampin in a Patient With
      Doxycycline Intolerance.
AB  - African tick bite fever is the most commonly encountered travel-associated
      rickettsiosis, occurring in as many as 5% of travelers returning from rural
      subequatorial Africa. This case report illustrates that rifampin represents an
      effective alternative to doxycycline for treatment of African tick bite fever in
      some selective situations.

PMID- 28505277
TI  - Esterification of Ibuprofen in Soft Gelatin Capsules Formulations-Identification,
      Synthesis and Liquid Chromatography Separation of the Degradation Products.
AB  - Unknown impurities were identified in ibuprofen (IBU) soft gelatin capsules
      (SGCs) during long-term stability testing by a UHPLC method with UV detection and
      its chemical formula was determined using high resolution/accurate mass (HRAM) LC
      MS. Reference standards of the impurities were subsequently synthesized, isolated
      by semi-preparative HPLC and characterized using HRAM LC-MS, NMR and IR. Two
      impurities were formed by esterification of IBU with polyethylene glycol (PEG),
      which is used as a fill of the SGCs, and were identified as IBU-PEG monoester and
      IBU-PEG diester. Two other degradants arised from reaction of IBU with sorbitol
      and sorbitan, which are components of the shell and serves as plasticizers. Thus,
      IBU sorbitol monoester (IBU-sorbitol) and IBU sorbitan monoester (IBU-sorbitan
      ester) were identified. An UHPLC method was further optimized in order to
      separate, selectively detect and quantify the degradation products in IBU SGCs.

PMID- 28505278
TI  - Cost-effectiveness of outpatient parenteral antibiotic therapy: a simulation
      modelling approach.
AB  - Objectives: In the UK, patients who require intravenous antimicrobial (IVA)
      treatment may receive this in the community through outpatient parenteral
      antimicrobial therapy (OPAT) services. Services include: IVA administration at a
      hospital outpatient clinic (HO); IVA administration at home by a general nurse
      (GN) or a specialist nurse (SN); or patient self-administered (SA) IVA
      administration following training. There is uncertainty regarding which OPAT
      services represent value for money; this study aimed to estimate their cost
      effectiveness. Methods: A cost-effectiveness decision-analytic model was
      developed using a simulation technique utilizing data from hospital records and a
      systematic review of the literature. The model estimates cost per QALY gained
      from the National Health Service (NHS) perspective for short- and long-term
      treatment of infections and service combinations across these. Results: In short
      term treatments, HO was estimated as the most effective (0.7239 QALYs), but at
      the highest cost (L973). SN was the least costly (L710), producing 0.7228 QALYs.
      The combination between SN and HO was estimated to produce 0.7235 QALYs at a cost
      of L841. For long-term treatments, SN was the most effective (0.677 QALYs),
      costing L2379, while SA was the least costly at L1883, producing 0.666 QALYs. A
      combination of SA and SN was estimated to produce 0.672 QALYs at a cost of L2128.
      Conclusions: SN and SA are cost-effective for short- and long-term treatment of
      infections, while combining services may represent the second-best alternative
      for OPAT in the UK.

PMID- 28505280
TI  - Mining e-cigarette adverse events in social media using Bi-LSTM recurrent neural
      network with word embedding representation.
AB  - Objective: Recent years have seen increased worldwide popularity of e-cigarette
      use. However, the risks of e-cigarettes are underexamined. Most e-cigarette
      adverse event studies have achieved low detection rates due to limited subject
      sample sizes in the experiments and surveys. Social media provides a large data
      repository of consumers' e-cigarette feedback and experiences, which are useful
      for e-cigarette safety surveillance. However, it is difficult to automatically
      interpret the informal and nontechnical consumer vocabulary about e-cigarettes in
      social media. This issue hinders the use of social media content for e-cigarette
      safety surveillance. Recent developments in deep neural network methods have
      shown promise for named entity extraction from noisy text. Motivated by these
      observations, we aimed to design a deep neural network approach to extract e
      cigarette safety information in social media. Methods: Our deep neural language
      model utilizes word embedding as the representation of text input and recognizes
      named entity types with the state-of-the-art Bidirectional Long Short-Term Memory
      (Bi-LSTM) Recurrent Neural Network. Results: Our Bi-LSTM model achieved the best
      performance compared to 3 baseline models, with a precision of 94.10%, a recall
      of 91.80%, and an F-measure of 92.94%. We identified 1591 unique adverse events
      and 9930 unique e-cigarette components (ie, chemicals, flavors, and devices) from
      our research testbed. Conclusion: Although the conditional random field baseline
      model had slightly better precision than our approach, our Bi-LSTM model achieved
      much higher recall, resulting in the best F-measure. Our method can be
      generalized to extract medical concepts from social media for other medical
      applications.

PMID- 28505281
TI  - Application of Partially Substituted 3,5-Dimethylphenylcarbamate-(3-(2-O-beta
      Cyclodextrin)-2-Hydroxypropoxy)-Propylsilyl-Appended Silica Particles as Chiral
      Stationary Phase for Multi-mode High-performance Liquid Chromatography.
AB  - A new type of partially substituted 3,5-dimethylphenylcarbamate-(3-(2-O-beta
      cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MP-CD-HPS)
      have been prepared by a convenient post-immobilization derivazition procedure.
      The MP-CD-HPS has been successfully used as chiral stationary phase (CSP) for
      high-performance liquid chromatography (HPLC) under normal phase, reversed phase
      and polar organic mobile phase conditions. The chromatographic evaluation results
      show that the MP-CD-HPS has excellent selectivity for the separation of aromatic
      positional isomers and enantiomers of some chiral compounds. The multi-mode HPLC
      separation results also indicate that both the stable ether spacer linking to the
      wider torus rim of beta-cyclodextrin in the MP-CD-HPS phase and the hydroxyl
      residues in the partially substituted beta-cyclodextrin have important
      contributions to chiral recognitions and chromatographic separations.

PMID- 28505282
TI  - Survival and Locomotory Behavior of Earwigs After Exposure to Reduced-Risk
      Insecticides.
AB  - The conservation of natural enemies is an important tactic to promote biological
      control of arthropod pests. The earwig Doru luteipes (Sccuder) is the most
      important predator of the fall armyworm Spodoptera frugiperda (J.E. Smith) in
      corn fields. One way of conserving these predators in the field is by using only
      selective insecticides when the pest population reaches the economic threshold.
      Some recent insecticides such as azadirachtin, chlorantraniliprole, and novaluron
      have been claimed to pose reduced risk for natural enemies. Nevertheless, there
      is a dearth of information regarding the selectivity of these insecticides upon
      earwigs in specific. In this study, we carried out a series of laboratory assays
      to examine the survivorship and locomotory behavior of D. luteipes after exposure
      to fresh dry residue of azadirachtin, chlorantraniliprole, and novaluron. Our
      results show a significant survival reduction for D. luteipes nymphs exposed to
      fresh residues of chlorantraniliprole and novaluron. In the behavioral studies,
      adults of D. luteipes stopped more often, spent more time resting (inactive), and
      moved more slowly immediately after exposure to chlorantraniliprole residue.
      These results suggest that chlorantraniliprole may mediate an impaired movement
      and a behavior arrestment of earwigs after contact with this insecticide fresh
      residue. This could translate into reduced foraging efficiency, and increase
      exposure and insecticide uptake. Although chlorantraniliprole and novaluron
      showed a potential to undermine the biological control provided by earwigs, it is
      yet essential to conduct field trials in order to confirm our laboratory results.

PMID- 28505279
TI  - Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease.
AB  - Context: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have
      been recently identified as the most common genetic alteration in patients with
      Cushing disease (CD). However, the frequency of these mutations in the pediatric
      population has not been extensively assessed. Objective: We investigated the
      status of the USP8 gene at the somatic level in a cohort of pediatric patients
      with corticotroph adenomas. Design and Methods: The USP8 gene was fully sequenced
      in both germline and tumor DNA samples from 42 pediatric patients with CD.
      Clinical, biochemical, and imaging data were compared between patients with and
      without somatic USP8 mutations. Results: Five different USP8 mutations (three
      missense, one frameshift, and one in-frame deletion) were identified in 13
      patients (31%), all of them located in exon 14 at the previously described
      mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients
      with somatic mutations were older at disease presentation [mean 5.1 +/- 2.1
      standard deviation (SD) vs 13.1 +/- 3.6 years, P = 0.03]. Levels of urinary free
      cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as
      tumor size and frequency of invasion of the cavernous sinus, were not
      significantly different between the two groups. However, patients harboring
      somatic USP8 mutations had a higher likelihood of recurrence compared with
      patients without mutations (46.2% vs 10.3%, P = 0.009). Conclusion: Somatic USP8
      gene mutations are a common cause of pediatric CD. Patients harboring a somatic
      mutation had a higher likelihood of tumor recurrence, highlighting the potential
      importance of this molecular defect for the disease prognosis and the development
      of targeted therapeutic options.

PMID- 28505283
TI  - Oxidative Injury and Iron Redistribution Are Pathological Hallmarks of Marmoset
      Experimental Autoimmune Encephalomyelitis.
AB  - Oxidative damage and iron redistribution are associated with the pathogenesis and
      progression of multiple sclerosis (MS), but these aspects are not entirely
      replicated in rodent experimental autoimmune encephalomyelitis (EAE) models.
      Here, we report that oxidative burst and injury as well as redistribution of iron
      are hallmarks of the MS-like pathology in the EAE model in the common marmoset.
      Active lesions in the marmoset EAE brain display increased expression of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox,
      and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions
      with active inflammation and demyelination, coinciding with enhanced expression
      of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE
      lesion-associated liberation of iron (due to loss of iron-containing myelin) was
      associated with altered expression of the iron metabolic markers FtH1,
      lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative
      damage markers in inflammatory lesions indicates that the enhanced antioxidant
      enzyme expression could not counteract reactive oxygen and nitrogen species
      induced cellular damage, as is also observed in MS brains. This study
      demonstrates that oxidative injury and aberrant iron distribution are prominent
      pathological hallmarks of marmoset EAE thus making this model suitable for
      therapeutic intervention studies aimed at reducing oxidative stress and
      associated iron dysmetabolism.

PMID- 28505285
TI  - Defining Pediatric Diarrhea in Low-Resource Settings.
AB  - Differences in definitions of acute pediatric diarrhea result in variable
      estimates of morbidity and mortality, treatment coverage, and associations with
      risk factors and outcomes. We reviewed published literature and guidelines
      focused on acute pediatric diarrhea in low- and middle-income countries. Clinical
      guidelines most commonly defined diarrhea in terms of quantity of loose or watery
      stool with consideration of normal stool patterns, whereas research studies often
      relied exclusively on a quantitative definition. The most commonly used
      quantitative definition, >=3 loose or watery stools in a 24-hour period, has been
      compared to gold standards of caregiver perception and visual inspection of
      stool, with variable agreement. Age, breast-feeding status, and setting (facility
      vs household-based) influence the performance of quantitative diarrhea
      definitions in children. Universal adoption of a set of valid gold standard
      definitions specifically aligned with various programmatic and research goals
      will lead to more accurate coverage estimates and better-informed resource
      prioritization.

PMID- 28505284
TI  - Pathogenic Anti-Mullerian Hormone Variants in Polycystic Ovary Syndrome.
AB  - Context: Polycystic ovary syndrome (PCOS), a common endocrine condition, is the
      leading cause of anovulatory infertility. Objective: Given that common disease
      susceptibility variants account for only a small percentage of the estimated PCOS
      heritability, we tested the hypothesis that rare variants contribute to this
      deficit in heritability. Design, Setting, and Participants: Unbiased whole-genome
      sequencing (WGS) of 80 patients with PCOS and 24 reproductively normal control
      subjects identified potentially deleterious variants in AMH, the gene encoding
      anti-Mullerian hormone (AMH). Targeted sequencing of AMH of 643 patients with
      PCOS and 153 control patients was used to replicate WGS findings. Main Outcome
      Measures: Dual luciferase reporter assays measured the impact of the variants on
      downstream AMH signaling. Results: We found 24 rare (minor allele frequency <
      0.01) AMH variants in patients with PCOS and control subjects; 18 variants were
      specific to women with PCOS. Seventeen of 18 (94%) PCOS-specific variants had
      significantly reduced AMH signaling, whereas none of 6 variants observed in
      control subjects showed significant defects in signaling. Thus, we identified
      rare AMH coding variants that reduced AMH-mediated signaling in a subset of
      patients with PCOS. Conclusion: To our knowledge, this study is the first to
      identify rare genetic variants associated with a common PCOS phenotype. Our
      findings suggest decreased AMH signaling as a mechanism for the pathogenesis of
      PCOS. AMH decreases androgen biosynthesis by inhibiting CYP17 activity; a
      potential mechanism of action for AMH variants in PCOS, therefore, is to increase
      androgen biosynthesis due to decreased AMH-mediated inhibition of CYP17 activity.

PMID- 28505287
TI  - Anti-Helicobacter pylori activity of non-living, heat-killed form of lactobacilli
      including Lactobacillus johnsonii No.1088.
AB  - Some strains of lactic acid bacteria are reported to inhibit the growth of
      Helicobacter pylori and proposed to be useful to support so-called triple therapy
      for H. pylori. Although most strains must be alive to exert their anti-H. pylori
      activity, some lactobacilli strains are effective even when dead. One possible
      underlying mechanism of such an activity of non-living lactobacilli is reportedly
      co-aggregation with H. pylori. In this study, we found that a non-living heat
      killed form of Lactobacillus johnsonii No.1088 (HK-LJ88) and also that of some
      other lactobacilli inhibited the growth of H. pylori in vitro. Furthermore, the
      number of H. pylori in the infected stomach of germ-free mice was significantly
      decreased by the repeated oral administration of HK-LJ88. Observation by scanning
      electron microscopy revealed that no co-aggregation had occurred between H.
      pylori and HK-LJ88; instead, deformations of H. pylori (e.g. disappearance of
      spiral, bending of cell body, coccoid formation, degradations, etc.) appeared
      after incubation for 24 h with HK-LJ88. These results suggest that HK-LJ88
      inhibited H. pylori activity probably not by co-aggregation but by some unknown
      mechanism involving HK-LJ88's cell surface molecules and that even non-living
      lactobacilli are possibly useful to support H. pylori eradication therapy.

PMID- 28505288
TI  - Effect of different antibiotics on biofilm produced by uropathogenic Escherichia
      coli isolated from children with urinary tract infection.
AB  - Recurrent urinary tract infections (UTIs) occur frequently in children and women.
      Intracellular bacterial communities (IBCs) and biofilm formation by Escherichia
      coli are risk factors for recurrence. The aim of this study was to evaluate the
      effect of different antibiotics on biofilms by E. coli strains isolated from
      children with UTI and to correlate virulence factors and IBCs with biofilm
      formation. A total of 116 E. coli strains were tested for biofilm formation using
      the crystal violet microplate technique. 58.6% of the strains did not produce
      biofilm, while 16.4%, 18.1% and 6.8% formed weak, moderate and strong biofilms,
      respectively. No correlation was found between the ability to form biofilms and
      the presence of IBCs. Biofilm formation was significantly associated with pili P
      codifying genes, whereas other virulence factors were not statistically
      associated. Antibiotics, including ampicillin, cephalothin, ceftriaxone,
      ceftazidime, amikacin and ciprofloxacin, were evaluated at different
      concentrations after 48 h of biofilm formation. Except ampicillin, the other
      antibiotics tested induced a significant reduction of biofilm biomass. In the
      case of recurrent UTIs potentially associated with the presence of biofilm, the
      use of third-generation cephalosporin, fluoroquinolones and aminoglycosides could
      be recommended. These antibiotics demonstrated to reduce biofilm biomass produced
      even by resistant strains.

PMID- 28505286
TI  - PIXiE: an algorithm for automated ion mobility arrival time extraction and
      collision cross section calculation using global data association.
AB  - Motivation: Drift tube ion mobility spectrometry coupled with mass spectrometry
      (DTIMS-MS) is increasingly implemented in high throughput omics workflows, and
      new informatics approaches are necessary for processing the associated data. To
      automatically extract arrival times for molecules measured by DTIMS at multiple
      electric fields and compute their associated collisional cross sections (CCS), we
      created the PNNL Ion Mobility Cross Section Extractor (PIXiE). The primary
      application presented for this algorithm is the extraction of data that can then
      be used to create a reference library of experimental CCS values for use in high
      throughput omics analyses. Results: We demonstrate the utility of this approach
      by automatically extracting arrival times and calculating the associated CCSs for
      a set of endogenous metabolites and xenobiotics. The PIXiE-generated CCS values
      were within error of those calculated using commercially available instrument
      vendor software. Availability and implementation: PIXiE is an open-source tool,
      freely available on Github. The documentation, source code of the software, and a
      GUI can be found at https://github.com/PNNL-Comp-Mass-Spec/PIXiE and the source
      code of the backend workflow library used by PIXiE can be found at
      https://github.com/PNNL-Comp-Mass-Spec/IMS-Informed-Library . Contact:
      erin.baker@pnnl.gov or thomas.metz@pnnl.gov. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 28505289
TI  - Financial and environmental costs of reusable and single-use anaesthetic
      equipment.
AB  - Background.: An innovative approach to choosing hospital equipment is to consider
      the environmental costs in addition to other costs and benefits. Methods.: We
      used life cycle assessment to model the environmental and financial costs of
      different scenarios of replacing reusable anaesthetic equipment with single-use
      variants. The primary environmental costs were CO 2 emissions (in CO 2
      equivalents) and water use (in litres). We compared energy source mixes between
      Australia, the UK/Europe, and the USA. Results.: For an Australian hospital with
      six operating rooms, the annual financial cost of converting from single-use
      equipment to reusable anaesthetic equipment would be an AUD$32 033 (L19 220), 46%
      decrease. In Australia, converting from single-use to reusable equipment would
      result in an increase of CO 2 emissions from 5095 (95% CI: 4614-5658) to 5575 kg
      CO 2 eq (95% CI: 5542-5608), a 480 kg CO 2 eq (9%) increase. Using the
      UK/European power mix, converting from single-use (5575 kg CO 2 eq) to reusable
      anaesthetic equipment (802 kg CO 2 eq) would result in an 84% reduction (4873 kg
      CO 2 eq) in CO 2 emissions, whilst in the USA converting to reusables would have
      led to a 2427 kg CO 2 eq (48%) reduction. In Australia, converting from single
      use to reusable equipment would more than double water use from 34.4 to 90.6
      kilolitres. Conclusions.: For an Australian hospital with six operating rooms,
      converting from single-use to reusable anaesthetic equipment saved more than
      AUD$30 000 (L18 000) per annum, but increased the CO 2 emissions by almost 10%.
      The CO 2 offset is highly dependent on the power source mix, while water
      consumption is greater for reusable equipment.

PMID- 28505292
TI  - Effect of Auricular Point Acupressure on Axial Neck Pain After Anterior Cervical
      Discectomy and Fusion: A Randomized Controlled Trial.
AB  - Objectives: To evaluate the effect of auricular point acupressure (APA) on axial
      neck pain after anterior cervical discectomy and fusion (ACDF) surgery. Design: A
      prospective randomized controlled trial was performed. Subjects and setting:
      Twenty-nine participants were randomly divided into two groups, real or sham APA.
      Participants were enrolled from Shaoxing Hospital of Traditional Chinese
      Medicine, affiliated with Zhejiang Chinese Medical University. Methods: Eligible
      participants received a four-week real or sham APA treatment according to their
      assigned groups. The clinical outcomes were assessed by the criteria of Hosono et
      al., the Brief Pain Inventory Short Form (BPI), and the 36-item Short Form Health
      Survey (SF-36). In addition, plasma interleukin (IL)-1beta, IL-6, and tumor
      necrosis factor (TNF)-alpha were analyzed. Results: Patients with severe or
      moderate axial neck pain accounted for 28.6% and 35.7% in the real APA group at
      the end of treatment and one-month follow-up. BPI scores were decreased in the
      real APA group at the end of treatment and one-month follow-up. The total mean
      score of SF-36 was improved in the real APA group and significantly higher than
      in the sham APA group. Additional, the levels of IL-1beta, IL-6, and TNF-alpha
      were decreased in the real APA group. Conclusions: The findings supported the
      therapeutic effect of APA treatment on axial neck pain after ACDF surgery, and
      they exert the possible therapeutic effect on downregulating the levels of plasma
      IL-1beta, IL-6, and TNF-alpha.

PMID- 28505290
TI  - Supraphysiologic estradiol is an independent predictor of low birth weight in
      full-term singletons born after fresh embryo transfer.
AB  - STUDY QUESTION: Is supraphysiologic estradiol (E2) an independent predictor of
      low birth weight (LBW) in singletons born after fresh IVF-embryo transfer (ET)
      cycles? SUMMARY ANSWER: Our results suggest that E2 > 2500 pg/ml is an
      independent predictor for LBW in full-term singletons born to normal responder
      patients undergoing fresh IVF-ET cycles. WHAT IS KNOWN ALREADY: The pathogenesis
      of LBW in IVF singletons remains unknown. However, recent studies have suggested
      that the hyperestrogenic milieu generated during ovarian stimulation may create a
      sub-optimal peri-implantation environment, leading to placental dysfunction, and
      therefore, LBW. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of
      normal responder patients, <40 years old, undergoing fresh IVF-ET cycles
      resulting in live singleton births between January 2005 and June 2014.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 6419 patients had live
      births after fresh IVF-ET during the study period, of which 2348 (36.6%) patients
      were excluded due to multiple gestation, vanishing twins or incomplete records.
      Perinatal outcomes recorded for all patients included birth weight, gestational
      age (GA) at delivery, mode of delivery and gender. Term birth, preterm birth
      (PTB) and LBW incidence proportions were plotted against E2 level on the day of
      trigger. The term LBW incidence proportion (i.e. singletons born at GA >= 37
      weeks with birth weight <2500 g) was considered the primary outcome of interest.
      MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4071 patients with live singleton
      births were included. The median age, BMI, E2 level and birth weight for the
      study cohort was 36 (33-39) years, 22.3 (20.4-25.0) kg/m2, 1554 (1112.7-2179)
      pg/ml and 3289 (2920-3628) g, respectively. The incidence proportion of LBW rose
      from 6.4% (E2 2001-2500 pg/ml) to 20.7% (E2 3501-4000 pg/ml), without a
      corresponding rise in the incidence proportion of PTB. The odds of term LBW with
      E2 > 2500 pg/ml were 6.1-7.9 times higher compared to the referent E2 group.
      Multivariable logistic regression analysis revealed that E2 was an independent
      predictor for term LBW, even after adjusting for age, BMI, race, parity,
      infertility diagnosis, duration of ovarian stimulation, gonadotropin dosage and
      method of insemination (adjusted odds ratio 10.8, 95% CI 9.2-12.5). Receiver
      operating characteristic analysis generated an AUC estimate of 0.85 for E2 level
      as a predictor of LBW. LIMITATIONS REASONS FOR CAUTION: The current study did not
      include analyses of hypertensive disorders of pregnancy or placental
      abnormalities. Furthermore, all patients were normal responders and of normal
      BMI, possibly limiting the overall generalizability of the study. Finally, as
      with any retrospective study, prospective data are required to validate the role
      of E2 in predicting LBW. WIDER IMPLICATIONS OF THE FINDINGS: Our results
      emphasize the importance of minimizing the supraphysiologic elevations of E2
      levels during ovarian stimulation in fresh IVF-ET cycles. This, in turn, can
      optimize the early peri-implantation environment and mitigate adverse perinatal
      outcomes such as LBW. STUDY FUNDING/COMPETING INTEREST(S): Dr Paul J. Christos
      was partially supported by the following grant: Clinical and Translational
      Science Center at Weill Cornell Medical College (UL1-TR000457-06). TRIAL
      REGISTRATION NUMBER: N/A.

PMID- 28505293
TI  - Budesonide MMX in Paediatric Patients With Ulcerative Colitis.

PMID- 28505291
TI  - Comparison of the Simplified sWHI and the Standard CHS Frailty Phenotypes for
      Prediction of Mortality, Incident Falls, and Hip Fractures in Older Women.
AB  - Background: We compared the simplified Women's Health Initiative (sWHI) and the
      standard Cardiovascular Health Study (CHS) frailty phenotypes in predicting
      falls, hip fracture, and death in older women. Methods: Participants are from the
      WHI Clinical Trial. CHS frailty criteria included weight loss, exhaustion,
      weakness, slowness, and low physical activity. The sWHI frailty score used two
      items from the RAND-36 physical function and vitality subscales, one item from
      the WHI physical activity scale plus the CHS weight loss criteria. Specifically,
      level of physical function was the capacity to walk one block and scored as
      severe (2-points), moderate (1-point), or no limitation (0). Vitality was based
      on feeling tired most or all of the time (1-point) versus less often (0). Low
      physical activity was walking outside less than twice a week (1-point) versus
      more often (0). A total score of 3 resulted in a frailty classification, a score
      of 1 or 2 defined pre-frailty, and 0 indicated nonfrailty. Outcomes were modeled
      using Cox regression and Harrell C-statistics were used for comparisons. Results:
      Approximately 5% of the participants were frail based on the CHS or sWHI
      phenotype. The sWHI frailty phenotype was associated with higher rates of
      mortality (hazard ratio [HR] = 2.36, p <= .001) and falls (HR = 1.45, p = .005).
      Comparable HRs in CHS-phenotype were 1.97 (p < .001) and 1.36 (p = .03),
      respectively. Neither phenotype predicted hip fracture. Harrell C-statistics
      revealed nonsignificant differences in HRs between the CHS and sWHI frailty
      phenotypes. Conclusion: The sWHI phenotype, which is self-reported and brief,
      might be practical in settings with limited resources.

PMID- 28505294
TI  - Anticalcification effect of a combination of decellularization, organic solvents
      and amino acid detoxification on glutaraldehyde-fixed xenopericardial heart
      valves in a large-animal long-term circulatory model.
AB  - OBJECTIVES: We aimed to investigate the effect of a combination of
      anticalcification treatments, which were effective for preventing calcification
      in a small animal experiment, on glutaraldehyde-fixed xenopericardial valves
      using a large-animal long-term circulatory model. METHODS: Valved conduits were
      made of porcine pericardium as a leaflet and bovine pericardium as a conduit and
      were implanted into the right ventricular outflow tract of goats under
      cardiopulmonary bypass. The goats were divided into study (glutaraldehyde +
      combined anticalcification treatment, n = 6) and control (glutaraldehyde alone, n
      = 9) groups. Upon euthanization at 1 year, echocardiography and cardiac
      catheterization were performed. Explanted tissues were microscopically examined
      and analysed for measuring the calcium content. RESULTS: Haemodynamic data were
      obtained from 3 and 2 goats in the study and control groups, respectively. All
      valves, except 1, which was limited in motion, were functioning well on
      echocardiography; pressure gradients across the right ventricular outflow tract
      were lower in the study group on cardiac catheterization. On gross inspection,
      all leaflets remained mobile without calcific deposits in the study group, while
      most leaflets were heavily calcified in the control group. The calcium content in
      the leaflets remained low (<=4 ug/mg) in the study group. Among the leaflets
      explanted from goats that survived longer (>3 months), the calcium concentration
      was higher in the control group than in the study group [15.1 ug/mg (n = 5) vs
      2.7 ug/mg (n = 5), respectively; P = 0.008). CONCLUSIONS: Porcine pericardial
      leaflets treated with our anticalcification protocol showed better function and
      less calcification than those treated with glutaraldehyde alone in the pulmonary
      position.

PMID- 28505295
TI  - Phylogenetic distribution of tir-cytoskeleton coupling protein (tccP and tccP2)
      genes in atypical enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) strains employ the type III secretion
      system (T3SS) effector Tir to induce actin cytoskeletal rearrangements. While
      some EPEC require tyrosine phosphorylation (Y-P) of Tir to trigger actin
      assembling, certain strains whose Tir is not tyrosine phosphorylated utilize the
      T3SS effector Tir-cytoskeleton coupling protein (TccP/TccP2) for efficient actin
      polymerization. The presence of tccP/tccP2 in typical EPEC belonging to distinct
      evolutionary lineages is well established but, in contrast, little is known about
      the distribution of these genes in atypical EPEC (aEPEC) showing distinct
      phylogenetic background. In this study, we screened 72 pathogenic aEPEC for the
      presence of tccP/tccP2 genes, and further characterized positive strains
      regarding tir type, phylogroups and production of TccP/TccP2. The tccP and/or
      tccP2 genes were detected in 45.8% of the strains, with a predominance of tccP2
      allele. Most of these strains carried tirY-P, suggesting that can trigger actin
      polymerization using both Tir tyrosine phosphorylation and TccP/TccP2 pathways.
      aEPEC strains carrying tccP or tccP2 were significantly associated to phylogroups
      E and B1, respectively. We also observed a strain-to-strain variation regarding
      TccP/TccP2 production. Our results demonstrate a wide distribution of tccP/tccP2
      genes among pathogenic aEPEC strains, as well associations between specific
      alleles and phylogenetic backgrounds.

PMID- 28505297
TI  - Reply to Jones et al.

PMID- 28505296
TI  - Varenicline is associated with a modest limitation in weight gain in smokers
      after smoking cessation: a meta-analysis.
AB  - Objective: To assess the effect of treatment on limiting weight gain in
      abstainers using and not using varenicline and during the nontreatment phase.
      Methods: The PubMed, Medline, EMBASE and Cochrane Library databases were searched
      to identify relevant studies published in English or Chinese. A meta-analysis was
      performed to calculate pooled weighted mean differences (WMDs) in weight gain in
      smokers after smoking cessation between varenicline and control groups and their
      corresponding 95% CIs. The I2 statistic was used to measure heterogeneity.
      Publication bias was evaluated using Egger's regression asymmetry test. Results:
      A total of 10 studies were included. The WMD in weight gain in abstainers between
      varenicline and control groups was -0.23 kg (95% CI: -0.36 to -0.09, P < 0.05).
      Moreover, the result of the subgroup analysis by timepoint of weight measurement
      indicated that the WMD in weight gain in smokers after smoking cessation between
      varenicline and control groups after the 12-week treatment phase was -0.23 kg
      (95% CI: -0.37 to -0.08, P < 0.05), and the WMD observed during the nontreatment
      follow-up phase was -0.69 kg (95% CI: -2.15 to 0.77, P > 0.05). In addition, the
      result of the subgroup analysis by type of control showed that the WMD in weight
      gain in abstainers from smoking between the varenicline and placebo groups was 
      0.29 kg (95% CI: -0.46 to -0.12, P < 0.05), and the WMD between the varenicline
      and other control groups was -0.20 kg (95% CI: -0.77 to 0.37, P > 0.05).
      Conclusion: Varenicline was associated with a modest limitation in weight gain in
      smokers after smoking cessation; however, the impact of varenicline use was not
      long-term, and, in fact, no different from that of the placebo treatment.

PMID- 28505298
TI  - Early health outcome and 10-year survival in patients undergoing redo coronary
      surgery with or without cardiopulmonary bypass: a propensity score-matched
      analysis.
AB  - OBJECTIVES: To investigate the in-hospital health outcome and 10-year survival in
      patients undergoing redo coronary surgery with (redo-CABG) or without (redo
      OPCAB) cardiopulmonary bypass. METHODS: A total of 349 redo coronary surgery
      patients were identified from our registry. Of these, 143 redo-OPCAB patients
      (40.97%) were compared with 206 redo-CABG patients. To minimize the bias, we also
      conducted propensity score matching. In Matched Analysis A, 111 redo-OPCAB
      patients with any type of primary cardiac operation were compared with 111 redo
      CABG cases. In Matched Analysis B, 84 redo-OPCAB patients with isolated coronary
      surgery as their primary operation were compared with 84 redo-CABG patients. We
      assessed for all 3 analyses a composite of in-hospital mortality, acute kidney
      injury, stroke and severe low cardiac output requiring intra-aortic balloon pump.
      In addition, we assessed 1-, 5-, and 10-year survival. RESULTS: In the unmatched
      analysis, redo-CABG was associated with higher usage of intra-aortic balloon pump
      (10 vs 3%, P = 0.01) and composite compared with redo-OPCAB (25 vs 16%, P = 0.06)
      and similar 10-year survival (67.2 vs 68.5%, log-rank test: P = 0.78). Matched
      Analysis A showed similar rates of composite (15 vs 21%, P = 0.25) and 10-year
      survival (65.1 vs 60.8%, log-rank test: P = 0.5). Matched Analysis B showed
      reduction of the composite (19 vs 8%, P = 0.04), less in-hospital mortality (5 vs
      0%, P = 0.13), 4.5 times less need for intra-aortic balloon pump (2 vs 11%, P =
      0.02) favouring redo-OPCAB and a similar 10-year survival (71.6 vs 71.7%, log
      rank test: P = 0.61). CONCLUSIONS: Redo-OPCAB surgery is feasible, safe and
      effective with improved in-hospital outcome and similar 10-year survival compared
      to redo-CABG.

PMID- 28505299
TI  - Measuring vaccination coverage better will help achieve disease control.
AB  - Timely and accurate measurement of vaccination coverage is required to evaluate
      the success of vaccine programmes as well as identifying susceptible groups in
      order to better control disease. Estimating coverage requires knowledge of how
      many people are eligible for vaccination, and how many have received the vaccine.
      Achieving this presents a number of challenges in both high and low income
      settings. Investing in systems that record vaccination coverage better, as an
      integral part of vaccine strategies, will be a step towards better control of
      vaccine-preventable diseases.

PMID- 28505300
TI  - Impact of glutathione metabolism on zinc homeostasis in Saccharomyces cerevisiae.
AB  - Zinc is a crucial mineral for all organisms as it is an essential cofactor for
      the proper function of a plethora of proteins and depletion of zinc causes
      oxidative stress. Glutathione is the major redox buffering agent in the cell and
      therefore important for mitigation of the adverse effects of oxidative stress. In
      mammalian cells, zinc deficiency is accompanied by a glutathione depletion. In
      the yeast Saccharomyces cerevisiae, the opposite effect is observed: under low
      zinc conditions, an elevated glutathione concentration is found. The main
      regulator to overcome zinc deficiency is Zap1p. However, we show that Zap1p is
      not involved in this glutathione accumulation phenotype. Furthermore, we found
      that in glutathione-accumulating strains also the metal ion-binding phytochelatin
      2, which is an oligomer of glutathione, is accumulated. This increased
      phytochelatin concentration correlates with a lower free zinc level in the
      vacuole. These results suggest that phytochelatin is important for zinc buffering
      in S. cerevisiae and thus explains how zinc homeostasis is connected with
      glutathione metabolism.

PMID- 28505301
TI  - Two New Species of the Simulium (Simulium) variegatum Species-Group of Black
      Flies (Diptera: Simuliidae) From Thailand.
AB  - Two new species of black flies, Simulium (Simulium) srisukai and S. (S.)
      kiewmaepanense, are described from specimens collected in Thailand. Both species
      are assigned to the Simulium variegatum species-group of the subgenus Simulium
      (Simulium) Latreille. They are characterized by the darkened female femora and
      tibiae and six inflated pupal gill filaments, and the darkened female tibiae and
      six ordinary thread-like pupal gill filaments, respectively. Taxonomic notes are
      given to separate these new species from 10 related species among the group.
      These new species represent the third and fourth species of the S. variegatum
      species-group from Thailand.

PMID- 28505302
TI  - The Whole-Genome and Transcriptome of the Manila Clam (Ruditapes philippinarum).
AB  - The manila clam, Ruditapes philippinarum, is an important bivalve species in
      worldwide aquaculture including Korea. The aquaculture production of R.
      philippinarum is under threat from diverse environmental factors including
      viruses, microorganisms, parasites, and water conditions with subsequently
      declining production. In spite of its importance as a marine resource, the
      reference genome of R. philippinarum for comprehensive genetic studies is largely
      unexplored. Here, we report the de novo whole-genome and transcriptome assembly
      of R. philippinarum across three different tissues (foot, gill, and adductor
      muscle), and provide the basic data for advanced studies in selective breeding
      and disease control in order to obtain successful aquaculture systems. An
      approximately 2.56 Gb high quality whole-genome was assembled with various
      library construction methods. A total of 108,034 protein coding gene models were
      predicted and repetitive elements including simple sequence repeats and noncoding
      RNAs were identified to further understanding of the genetic background of R.
      philippinarum for genomics-assisted breeding. Comparative analysis with the
      bivalve marine invertebrates uncover that the gene family related to complement
      C1q was enriched. Furthermore, we performed transcriptome analysis with three
      different tissues in order to support genome annotation and then identified
      41,275 transcripts which were annotated. The R. philippinarum genome resource
      will markedly advance a wide range of potential genetic studies, a reference
      genome for comparative analysis of bivalve species and unraveling mechanisms of
      biological processes in molluscs. We believe that the R. philippinarum genome
      will serve as an initial platform for breeding better-quality clams using a
      genomic approach.

PMID- 28505303
TI  - Acute Effects of Aerobic Exercise on Affect and Smoking Craving in the Weeks
      Before and After a Cessation Attempt.
AB  - Introduction: Aerobic exercise may improve smoking abstinence via reductions in
      craving and negative affect and increases in positive moods. Acute changes in
      craving and affect before and after structured exercise sessions have not been
      examined during the weeks prior to and following quit attempts nor has smoking
      status been examined in relation to these effects. Given that regular cigarette
      smoking can be perceived as affect enhancing and craving reducing, it is not
      known whether exercise could contribute additional affective benefit beyond these
      effects. Method: Participants (N = 57; 68.4% women) were low-active daily smokers
      randomized to cessation treatments plus either group-based aerobic exercise (AE)
      or a health-education control (HEC). Mood, anxiety, and craving were assessed
      before and after each intervention session for each of the 12 weeks. Carbon
      monoxide (CO) breath samples <= 5ppm indicated smoking abstinence. Results:
      During the prequit sessions, significantly greater decreases in anxiety following
      AE sessions relative to HEC sessions were observed. Changes in mood and craving
      were similar after AE and HEC sessions prior to quitting. Postquit attempt,
      significant reductions in craving and anxiety were observed after AE sessions but
      not following HEC. During the postquit period, positive mood increased following
      AE sessions relative to HEC only among individuals who were abstinence on that
      day. Conclusions: AE may be effective in acutely reducing anxiety prior to a quit
      attempt and both anxiety and craving following the quit attempt regardless of
      abstinence status. The mood-enhancing effects of AE may occur only in the context
      of smoking abstinence. Implications: The current findings underscore the
      importance of examining the acute effects of aerobic exercise prior to and after
      a cessation attempt and as a function of smoking status. Given the equivocal
      results from previous studies on the efficacy of exercise for smoking cessation,
      increasing our understanding of how aerobic exercise produces its reinforcing
      benefits for smokers attempting to quit could potentially inform the refinement
      (e.g., timing/sequencing) of exercise interventions within smoking cessation
      programs.

PMID- 28505304
TI  - Phytoplasma-conserved phyllogen proteins induce phyllody across the Plantae by
      degrading floral MADS domain proteins.
AB  - ABCE-class MADS domain transcription factors (MTFs) are key regulators of floral
      organ development in angiosperms. Aberrant expression of these genes can result
      in abnormal floral traits such as phyllody. Phyllogen is a virulence factor
      conserved in phytoplasmas, plant pathogenic bacteria of the class Mollicutes. It
      triggers phyllody in Arabidopsis thaliana by inducing degradation of A- and E
      class MTFs. However, it is still unknown whether phyllogen can induce phyllody in
      plants other than A. thaliana, although phytoplasma-associated phyllody symptoms
      are observed in a broad range of angiosperms. In this study, phyllogen was shown
      to cause phyllody phenotypes in several eudicot species belonging to three
      different families. Moreover, phyllogen can interact with MTFs of not only
      angiosperm species including eudicots and monocots but also gymnosperms and a
      fern, and induce their degradation. These results suggest that phyllogen induces
      phyllody in angiosperms and inhibits MTF function in diverse plant species.

PMID- 28505305
TI  - Efficacy and Safety of Ledipasvir/Sofosbuvir for the Treatment of Chronic
      Hepatitis C in Persons With Sickle Cell Disease.
AB  - Patients with sickle cell disease are at high risk for chronic hepatitis C
      infection. Prior treatment has been limited due to the use of ribavirin causing
      hemolytic anemia and interferon causing cytopenias. We demonstrate the safety and
      efficacy of fixed-dose combination ledipasvir and sofosbuvir for 12 weeks in this
      population.

PMID- 28505307
TI  - Sexual Dimorphism and Retinal Mosaic Diversification following the Evolution of a
      Violet Receptor in Butterflies.
AB  - Numerous animal lineages have expanded and diversified the opsin-based
      photoreceptors in their eyes underlying color vision behavior. However, the
      selective pressures giving rise to new photoreceptors and their spectral tuning
      remain mostly obscure. Previously, we identified a violet receptor (UV2) that is
      the result of a UV opsin gene duplication specific to Heliconius butterflies. At
      the same time the violet receptor evolved, Heliconius evolved UV-yellow
      coloration on their wings, due to the pigment 3-hydroxykynurenine (3-OHK) and the
      nanostructure architecture of the scale cells. In order to better understand the
      selective pressures giving rise to the violet receptor, we characterized opsin
      expression patterns using immunostaining (14 species) and RNA-Seq (18 species),
      and reconstructed evolutionary histories of visual traits in five major lineages
      within Heliconius and one species from the genus Eueides. Opsin expression
      patterns are hyperdiverse within Heliconius. We identified six unique retinal
      mosaics and three distinct forms of sexual dimorphism based on ommatidial types
      within the genus Heliconius. Additionally, phylogenetic analysis revealed
      independent losses of opsin expression, pseudogenization events, and relaxation
      of selection on UVRh2 in one lineage. Despite this diversity, the newly evolved
      violet receptor is retained across most species and sexes surveyed.
      Discriminability modeling of behaviorally preferred 3-OHK yellow wing coloration
      suggests that the violet receptor may facilitate Heliconius color vision in the
      context of conspecific recognition. Our observations give insights into the
      selective pressures underlying the origins of new visual receptors.

PMID- 28505306
TI  - Secretion of 2,3-dihydroxyisovalerate as a limiting factor for isobutanol
      production in Saccharomyces cerevisiae.
AB  - Isobutanol is a superior biofuel compared to ethanol, and it is naturally
      produced by yeasts. Previously, Saccharomyces cerevisiae has been genetically
      engineered to improve isobutanol production. We found that yeast cells engineered
      for a cytosolic isobutanol biosynthesis secrete large amounts of the intermediate
      2,3-dihydroxyisovalerate (DIV). This indicates that the enzyme dihydroxyacid
      dehydratase (Ilv3) is limiting the isobutanol pathway and/or yeast exhibit
      effective transport systems for the secretion of the intermediate, competing with
      isobutanol synthesis. Moreover, we found that DIV cannot be taken up by the cells
      again. To identify the responsible transporters, microarray analysis was
      performed with a DIV producing strain compared to a wild type. Altogether, 19
      genes encoding putative transporters were upregulated under DIV-producing
      conditions. Thirteen of these were deleted together with five homologous genes. A
      yro2 mrh1 deletion strain showed reduced DIV secretion, while a hxt5 deletion
      mutant showed increased isobutanol production. However, a strain deleted for all
      the 18 genes secreted even slightly increased amounts of the intermediates and
      less isobutanol. The lactate transporter Jen1 turned out to transport the
      intermediate 2-ketoisovalerate, but not DIV. The results suggest that the
      transport of DIV is a rather complex process and several unspecific transporters
      seem to be involved.

PMID- 28505308
TI  - Diagnostic Performance of Ultrasound-Guided Fine-Needle Aspiration of Nonpalpable
      Breast Lesions in a Multidisciplinary Setting: The Institut Curie's Experience.
AB  - Objectives: To assess the diagnostic performance of ultrasound-guided fine-needle
      aspiration (USFNA) in nonpalpable breast lesions (NPBLs) in a multidisciplinary
      setting. Methods: In total, 2,601 NPBLs underwent USFNA by a radiologist
      pathologist team. Gold-standard diagnosis was based on surgery, core-needle
      biopsy, or 1-year imaging follow-up. USFNA's diagnostic performance was analyzed
      in different clinical and imaging subgroups. Results: USFNA's sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      were, respectively, 92.6% (95% confidence interval [CI], 90.8%-94.2%), 96.8% (95%
      CI, 95.8%-97.6%), 94.8% (95% CI, 93.2%-96.1%), and 95.4% (95% CI, 94.3%-96.4%).
      The best PPV was achieved in Breast-Imaging Reporting and Data System (BI-RADS)
      categories 4C and 5 and the best NPV in BI-RADS categories 2, 3, and 4A and in
      patients younger than 50 years. The mitotic count, BI-RADS categories, associated
      palpable cancer, and age (<50 or >=50 years) were statistically independent
      factors ( P  < .05) between USFNA's false-negative and true-positive results.
      Conclusions: USFNA is a robust diagnostic procedure in NPBLs. Age and the BI-RADS
      category of the lesion are important factors determining its performance.

PMID- 28505310
TI  - Fact Finders-Clinical Perspectives.

PMID- 28505311
TI  - Aspirin wears smart.

PMID- 28505309
TI  - The herpes viral transcription factor ICP4 forms a novel DNA recognition complex.
AB  - The transcription factor ICP4 from herpes simplex virus has a central role in
      regulating the gene expression cascade which controls viral infection. Here we
      present the crystal structure of the functionally essential ICP4 DNA binding
      domain in complex with a segment from its own promoter, revealing a novel homo
      dimeric fold. We also studied the complex in solution by small angle X-Ray
      scattering, nuclear magnetic resonance and surface-plasmon resonance which
      indicated that, in addition to the globular domain, a flanking intrinsically
      disordered region also recognizes DNA. Together the data provides a rationale for
      the bi-partite nature of the ICP4 DNA recognition consensus sequence as the
      globular and disordered regions bind synergistically to adjacent DNA motifs.
      Therefore in common with its eukaryotic host, the viral transcription factor ICP4
      utilizes disordered regions to enhance the affinity and tune the specificity of
      DNA interactions in tandem with a globular domain.

PMID- 28505312
TI  - SODA: prediction of protein solubility from disorder and aggregation propensity.
AB  - Solubility is an important, albeit not well understood, feature determining
      protein behavior. It is of paramount importance in protein engineering, where
      similar folded proteins may behave in very different ways in solution. Here we
      present SODA, a novel method to predict the changes of protein solubility based
      on several physico-chemical properties of the protein. SODA uses the propensity
      of the protein sequence to aggregate as well as intrinsic disorder, plus
      hydrophobicity and secondary structure preferences to estimate changes in
      solubility. It has been trained and benchmarked on two different datasets. The
      comparison to other recently published methods shows that SODA has state-of-the
      art performance and is particularly well suited to predict mutations decreasing
      solubility. The method is fast, returning results for single mutations in
      seconds. A usage example estimating the full repertoire of mutations for a human
      germline antibody highlights several solubility hotspots on the surface. The web
      server, complete with RESTful interface and extensive help, can be accessed from
      URL: http://protein.bio.unipd.it/soda.

PMID- 28505314
TI  - Diversity of Mosquitoes (Diptera: Culicidae) Attracted to Human Subjects in
      Rubber Plantations, Secondary Forests, and Villages in Luang Prabang Province,
      Northern Lao PDR.
AB  - The impact of the rapid expansion of rubber plantations in South-East Asia on
      mosquito populations is uncertain. We compared the abundance and diversity of
      adult mosquitoes using human-baited traps in four typical rural habitats in
      northern Lao PDR: secondary forests, immature rubber plantations, mature rubber
      plantations, and villages. Generalized estimating equations were used to explore
      differences in mosquito abundance between habitats, and Simpson's diversity index
      was used to measure species diversity. Over nine months, 24,927 female mosquitoes
      were collected, including 51 species newly recorded in Lao PDR. A list of the 114
      mosquito species identified is included. More mosquitoes, including vector
      species, were collected in the secondary forest than immature rubber plantations
      (rainy season, odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31-0.36; dry
      season, 0.46, 95% CI 0.41-0.51), mature rubber plantations (rainy season, OR
      0.25, 95% CI 0.23-0.27; dry season, OR 0.25, 95% CI 0.22-0.28), and villages
      (rainy season, OR 0.13, 95% CI 0.12-0.14; dry season, 0.20, 95% CI 0.18-0.23).
      All habitats showed high species diversity (Simpson's indexes between 0.82-0.86)
      with vectors of dengue, Japanese encephalitis (JE), lymphatic filariasis, and
      malaria. In the secondary forests and rubber plantations, Aedes albopictus
      (Skuse), a dengue vector, was the dominant mosquito species, while in the
      villages, Culex vishnui (Theobald), a JE vector, was most common. This study has
      increased the overall knowledge of mosquito fauna in Lao PDR. The high abundance
      of Ae. albopictus in natural and man-made forests warrants concern, with vector
      control measures currently only implemented in cities and villages.

PMID- 28505315
TI  - Plasmid transfer efficiency using Lactoccocus lactis strains depends on
      invasiveness status but also on plasmid copy number.
AB  - Lactic acid bacteria as Lactococcus lactis are used as vector for protein but
      also DNA delivery into intestinal cells in vitro and in vivo. For the plasmid
      delivery strategy, the plasmid copy number per bacteria (PCN) is thus of great
      importance. The aim of this paper is to determine the physiological conditions
      when PCN is the highest in the bacteria. PCN was characterized by qPCR in five
      different recombinant Lactococcus lactis strains, containing one (mono-) or two
      different plasmids (biplasmidic), at exponential or stationary phase. We showed
      that in all cases but one, PCN is higher at exponential than stationary phase.
      PCN seems to depend on (i) monoplasmidic or biplasmidic strain; (ii) origin of
      replication of the plasmid; and (iii) the DNA load of the bacteria. Then we
      studied plasmid transfer in vitro from recombinant L. lactis to eukaryotic COS-7
      cells using culture at exponential or stationary phase. We showed that plasmid
      transfer can be improved in vitro by using bacteria at exponential phase.

PMID- 28505313
TI  - Structural study of the Fox-1 RRM protein hydration reveals a role for key water
      molecules in RRM-RNA recognition.
AB  - The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM
      protein family. We report a 1.8 A X-ray structure of the free Fox-1 containing
      six distinct monomers. We use this and the nuclear magnetic resonance (NMR)
      structure of the Fox-1 protein/RNA complex for molecular dynamics (MD) analyses
      of the structured hydration. The individual monomers of the X-ray structure show
      diverse hydration patterns, however, MD excellently reproduces the most occupied
      hydration sites. Simulations of the protein/RNA complex show hydration consistent
      with the isolated protein complemented by hydration sites specific to the
      protein/RNA interface. MD predicts intricate hydration sites with water-binding
      times extending up to hundreds of nanoseconds. We characterize two of them using
      NMR spectroscopy, RNA binding with switchSENSE and free-energy calculations of
      mutant proteins. Both hydration sites are experimentally confirmed and their
      abolishment reduces the binding free-energy. A quantitative agreement between
      theory and experiment is achieved for the S155A substitution but not for the
      S122A mutant. The S155 hydration site is evolutionarily conserved within the RRM
      domains. In conclusion, MD is an effective tool for predicting and interpreting
      the hydration patterns of protein/RNA complexes. Hydration is not easily
      detectable in NMR experiments but can affect stability of protein/RNA complexes.

PMID- 28505316
TI  - Pancreas Atrophy and Islet Amyloid Deposition in Patients With Elderly-Onset Type
      2 Diabetes.
AB  - Context: With prolonged life expectancy, we often encounter patients with elderly
      onset type 2 diabetes mellitus (eT2DM). Although the clinical features of eT2DM
      are suggested to be different from those in patients with middle-age-onset type 2
      diabetes mellitus (mT2DM), the islet pathologic features in eT2DM have not been
      addressed. Objective: We attempted to characterize the pancreatic pathology in
      eT2DM and sought its clinical implications. Materials and Methods: Pancreata from
      13 young nondiabetic (age, 20 to 29 years), 27 patients with mT2DM (age, 45 to 87
      years), 22 middle-age subjects without T2DM, 15 subjects with eT2DM (age, 85 to
      100 years), and 30 elderly subjects without T2DM were investigated. Together with
      conventional microscopic observations, morphometric analysis on the islet, islet
      endocrine cells, and amyloid deposition was conducted on immunostained sections.
      Results: The estimated age of diabetes onset was 80.8 +/- 1.4 years (mean +/-
      standard error) in the eT2DM group and that of the mT2DM group was 48.3 +/- 2.4
      years. The pancreatic weight was nearly 50% less in the eT2DM group than in the
      other groups, showing duct obstruction with epithelial hyperplasia, marked acinar
      atrophy, fibrosis, and amyloid deposition in the islet. The islet mass was
      significantly reduced in the eT2DM group. The amyloid volume density correlated
      inversely with the beta-cell volume density but not with the body mass index in
      the eT2DM group. Laboratory data showed mild elevation of serum amylase in the
      eT2DM group, although clinical signs and symptoms of pancreatitis were not
      apparent. Conclusions: eT2DM is distinct from mT2DM and characterized by pancreas
      atrophy, ductal lesions, and amyloid deposition.

PMID- 28505317
TI  - Comparative assessment of conventional and light-curable fluoride varnish in the
      prevention of enamel demineralization during fixed appliance therapy: a split
      mouth randomized controlled trial.
AB  - Objective: To evaluate the effects of single application of a conventional versus
      light-curable fluoride varnish (LCFV) on prevention of enamel demineralization
      during fixed orthodontic treatment over a 4 month period. Design: The research
      was designed as a split-mouth, randomized control trial (RCT). Methods: Twenty
      two patients requiring fixed orthodontic treatment with premolar extractions were
      included in the RCT. In each patient, two diagonal quadrants (i.e. upper right
      and lower left, or vice versa) were randomly assigned to receive conventional
      fluoride varnish or LCFV. After allocation of one intervention, the other
      diagonal quadrants received the second intervention. At specific time intervals,
      premolars were extracted and sectioned, and the demineralized lesion was assessed
      in each group. Main outcome measures: The primary outcome was demineralized
      enamel lesion depth (DELD) at the end of 45, 90, and 120 days. Randomization: A
      simple complete randomization list using random allocation rule (restricted
      randomization) was computer generated to ensure homogeneity of application of
      conventional or LCFV to each contralateral quadrant in a split-mouth design.
      Allocation concealment was not employed. Blinding: Blinding was done only for
      outcome assessor because of clinical limitations. Results: Twenty-two patients
      with 88 teeth were enrolled in the trial. After excluding the drop-outs, primary
      analysis was performed on 66 teeth distributed among two interventional groups.
      Mean difference between DELD among two groups was 36.6 um [95 per cent confidence
      interval (CI) 34.61-38.55] and 58.5 um [95 per cent confidence interval (CI)
      55.65-61.43] at 90 and 120 days, respectively. Cluster level analysis performed
      by Paired t-test showed that DELD was significantly higher (P < 0.001) in the
      conventional fluoride varnish group at the end of 90 and 120 days as compared to
      LCFV group. No adverse effect was observed in any patient. Limitations: Being a
      histologic study, the role of fluoride varnish could be assessed only for 4
      months. Conclusion: The result of this study indicate that single application of
      LCFV (ClinproTM XT) can prevent enamel demineralization for longer duration (for
      up to 4 months) of time as compared to conventional fluoride varnish (DuraphatTM,
      45 days) during fixed appliance therapy. Registration: The trial was registered
      retrospectively in the Clinical Trial Registry-India, number CTRI/2016/09/007232.

PMID- 28505318
TI  - Calcified cerebral embolism: what the clinician needs to know.

PMID- 28505319
TI  - Spinal cord ischaemia after endovascular aneurysm repair.
AB  - We report the case of a patient who developed paraparesis 2 days after
      endovascular aneurysm repair for a right common iliac aneurysm. The patient had
      undergone thoracic endovascular aortic repair. The left subclavian artery was
      occluded, but the left internal iliac artery was preserved. The patient fully
      recovered from the paralysis within 3 months. This case illustrates the
      importance of collateral blood supply to the spinal cord from the lumbosacral
      region, especially when other sources are occluded.

PMID- 28505320
TI  - Graph-based semi-supervised learning with genomic data integration using
      condition-responsive genes applied to phenotype classification.
AB  - Objective: Data integration methods that combine data from different molecular
      levels such as genome, epigenome, transcriptome, etc., have received a great deal
      of interest in the past few years. It has been demonstrated that the synergistic
      effects of different biological data types can boost learning capabilities and
      lead to a better understanding of the underlying interactions among molecular
      levels. Methods: In this paper we present a graph-based semi-supervised
      classification algorithm that incorporates latent biological knowledge in the
      form of biological pathways with gene expression and DNA methylation data. The
      process of graph construction from biological pathways is based on detecting
      condition-responsive genes, where 3 sets of genes are finally extracted: all
      condition responsive genes, high-frequency condition-responsive genes, and P
      value-filtered genes. Results: The proposed approach is applied to ovarian cancer
      data downloaded from the Human Genome Atlas. Extensive numerical experiments
      demonstrate superior performance of the proposed approach compared to other state
      of-the-art algorithms, including the latest graph-based classification
      techniques. Conclusions: Simulation results demonstrate that integrating various
      data types enhances classification performance and leads to a better
      understanding of interrelations between diverse omics data types. The proposed
      approach outperforms many of the state-of-the-art data integration algorithms.

PMID- 28505321
TI  - Attention Problems as a Predictor of Type 1 Diabetes Adherence and Metabolic
      Control Across Adolescence.
AB  - Objective: Management of type 1 diabetes is a difficult self-regulatory process
      requiring continued attention to complex regimen tasks. The purpose of this study
      was to examine whether youths' attention problems were associated with poorer
      adherence and HbA1c across time, and whether higher parental involvement reduced
      these associations. Methods: Adolescents with type 1 diabetes (N = 199, M age  =
      12.43 years, SD = 1.50) and their mothers rated youths' attention problems and
      adherence at three time points. Adolescents rated parents' diabetes-specific
      monitoring and behavioral involvement. HbA1c was collected from medical records.
      Results: Adolescents' (but not mothers') greater reports of attention problems
      compared with their average related to lower adherence across time. Adolescents'
      (but not mothers') reports of greater attention problems compared with their
      average related to lower adherence across time. Conclusions: Youth attention
      problems may help us understand poor adherence, and interventions to promote
      parental involvement may buffer this risk.

PMID- 28505323
TI  - The perception of spiritual health differences between citizens and physicians in
      the Czech Republic.
AB  - This paper focuses on a phenomenon known as spiritual health. Although the
      scientific literature defines the concept of this health component (in relation
      to other dimensions, i.e. physical, mental and social health), there is no
      agreement concerning its relation to religiousness. The aim of this research is
      to find out the views of citizens (n = 1810) and physicians (n = 1200) in the
      Czech Republic on the potential dimension of health in its spiritual mode, and on
      the understanding of its content by those who acknowledge its existence. One of
      the main research findings is that physicians in the Czech Republic acknowledge
      the existence of spiritual health (47.0%) to a significantly greater extent than
      citizens of the country (26.4%). In both groups of respondents, the understanding
      varies in the discourse of psychology (psychiatry), theology, in the preference
      for harmony, and in medical care. The acknowledgement of spiritual health depends
      strongly on gender (women acknowledge the existence of this phenomenon more than
      men), religious belief (religious physicians, as well as religious citizens and
      members and non-members of churches and religious societies, acknowledge the
      existence of spiritual health significantly more compared with atheists) and
      education (with increasing education the proportion of citizens who acknowledge
      the existence of spiritual health rises considerably-the highest proportion is
      found in university graduates). Spiritual health is shown to be an important
      public health issue, even in a strongly secularized society.

PMID- 28505324
TI  - Inequalities in smoking prevalence: a missed opportunity for tobacco control in
      Pakistan.
AB  - Background: Pakistan is one of the highest tobacco consuming countries in South
      Asia and consumption is increasing. To implement equity orientated tobacco
      control policies, the most vulnerable groups must be identified. We aimed to
      identify these groups using the Pakistan Demographic and Health Survey (PDHS)
      2012-13. Methods: Descriptive statistics, univariate and multivariate analyses
      were used to explore household and participant characteristics associated with
      smoking inside the home or tobacco smoking, respectively. Survey weights were
      used to give nationally representative findings. Results: Data for 12 931
      households, 3132 men and 13 538 women were examined. About 58.3% of surveyed
      households were smoke-free, 39.1% were exposed to indoor tobacco smoke every day,
      2.6% less frequently. Significantly more rural households were exposed to indoor
      tobacco smoke than urban households (45.2% versus 34.9%). Of men, 28.3% reported
      smoking compared with 1.3% of women. Smoking prevalence was higher in older age
      groups. Increasing wealth was associated with lower smoking prevalence and indoor
      smoking. For men, but not women, increasing education was associated with reduced
      smoking. Conclusions: Inequalities in smoking behaviour impose harm to those who
      can least afford the financial and health costs. Future tobacco control policies
      in Pakistan must be sensitive to gender, geography and socio-economic status.

PMID- 28505325
TI  - Expert Opinion #5.

PMID- 28505322
TI  - Exosomes in Toxicology: Relevance to Chemical Exposure and Pathogenesis of
      Environmentally Linked Diseases.
AB  - Chronic exposure to environmental toxins has been known to initiate or aggravate
      various neurological disorders, carcinomas and other adverse health effects.
      Uptake by naive cells of pathogenic factors such as danger-associated molecules,
      mRNAs, miRNAs or aggregated proteins leads to disruption in cellular homeostasis
      further resulting in inflammation and disease propagation. Although early
      research tended to focus solely on exosomal removal of unwanted cellular
      contents, more recent reports indicate that these nano-vesicles play an active
      role in intercellular signaling. Not only is the exosomal cargo cell type
      specific, but it also differs between healthy and dying cells. Moreover,
      following exosome uptake by naive cells, the contents from these vesicles can
      alter the fate of recipient cells. Since exosomes can traverse long distances,
      they can influence distantly located cells and tissues. This review briefly
      explores the role played by environmental toxins in stimulating exosome release
      in the context of progressive neurodegenerative diseases such as Alzheimer's,
      Parkinson's, and Huntington's, as well as certain cancers such as lung, liver,
      ovarian, and tracheal carcinomas.

PMID- 28505326
TI  - Incidence of Bactericera cockerelli (Hemiptera: Triozidae) Under Different
      Pesticide Regimes in the Lower Columbia Basin.
AB  - Zebra chip is a potato disease transmitted by the potato psyllid Bactericera
      cockerelli (Sulc) and distributed across several regions of the United States.
      Because of its potentially devastating effects, the disease represents a threat
      to the potato production and the industry particularly in the Pacific Northwest,
      where it was first detected in 2011. Efforts to control the disease primarily
      focus on managing the vector using pesticides. In this study, the effectiveness
      of two pesticide spray programs in 2012 ("FULL" and "REDUCED") and three in 2013
      ("FULL 1," "FULL 2," and "REDUCED") against the potato psyllid was evaluated.
      Yellow sticky cards were used to monitor the adults, whereas immatures were
      evaluated by sampling the leaves. Overall, the vector infestation level in both
      years was low. The mean total number of adults per trap in 2012 was 1.5, 5, and
      12 for "FULL," "REDUCED," and the control, respectively, while in 2013 was 10.3,
      20.7, 17.7, and 52 for "FULL 1," "FULL 2," "REDUCED," and the control,
      respectively. For each particular year, season-long regimes were most effective
      at controlling the pest than targeted applications; however, there was no
      statistical difference among regimes ("FULL" or "REDUCED") after early July, when
      the first psyllids were detected, until mid-August. Moreover, this number was
      similar to the control. Also, psyllid density was uniform across sticky traps,
      and no clear relationship was found between the proportion of Lso-infective
      psyllids and zebra chip disease intensity.

PMID- 28505329
TI  - ERRATUM.

PMID- 28505327
TI  - Histone Deacetylase Inhibitor SAHA Is a Promising Treatment of Cushing Disease.
AB  - Context: Remission failure following transsphenoidal surgery in Cushing disease
      (CD) from pituitary corticotroph tumors (CtTs) remains clinically challenging.
      Histone deacetylase inhibitors (HDACis) are antitumor drugs approved for clinical
      use, with the potential to affect adrenocorticotropin hormone (ACTH)
      hypersecretion by inhibiting pro-opiomelanocortin (POMC) transcription.
      Objective: Testing the efficacy of suberoylanilide hydroxamic acid (SAHA) on
      human and murine ACTH-secreting tumor (AtT-20) cells. Design: Cell viability,
      ACTH secretion (enzyme-linked immunosorbent assay), apoptosis, and gene
      expression profile were investigated on AtT-20 cells. In vivo efficacy was
      examined in an athymic nude mouse AtT-20 xenograft model. SAHA efficacy against
      human-derived corticotroph tumor (hCtT) (n = 8) was tested in vitro. Setting:
      National Institutes of Health. Intervention: SAHA (0.5 to 8 uM). Main Outcome
      Measures: AtT-20 and hCtT cell survival, in vitro/invivo ACTH measurements.
      Results: SAHA (1 uM) reduced AtT-20 viability to 75% at 24 hours, 43% at 48 hours
      (analysis of variance; P = 0.002). Apoptosis was confirmed with elevated BAX/Bcl2
      ratio and FACS. Intriguingly, early (3-hour) significant decline (70%; P <
      0.0001) of secreted ACTH and diminished POMC transcription was observed with SAHA
      (1 uM). Microarray analysis revealed a direct association between liver X
      receptor alpha (LXRalpha) and POMC expression. Accordingly, SAHA reduced LXRalpha
      in AtT-20 cells but not in normal murine corticotrophs. Xenografted nude-mice
      tumor involution (126 +/- 33/160 +/- 35 vs 337 +/- 49 mm3; P = 0.0005) was
      observed with 5-day intraperitoneal SAHA, with reversal of elevated ACTH (P <
      0.0001). SAHA did not affect serum ACTH in nontumor mice. Lastly, we confirmed
      that SAHA (1 uM/24 h) decreased hCtT survival (78.92%; P = 0.0007) and ACTH
      secretion (83.64%; P = 0.03). Conclusion: Our findings demonstrate SAHA's
      efficacy in reducing survival and ACTH secretion in AtT-20 and hCtT cells,
      providing a potential intervention for recurrent/unremitting CD.

PMID- 28505330
TI  - Acinetobacter baumannii transfers the blaNDM-1 gene via outer membrane vesicles.
AB  - Objectives: To investigate the transmission of the gene encoding New Delhi
      metallo-beta-lactamase-1 ( bla NDM-1 ) through outer membrane vesicles (OMVs)
      released from an Acinetobacter baumannii strain (A_115). Methods: Isolation and
      purification of OMVs by density gradient from a carbapenem-resistant clinical
      strain of A. baumannii harbouring plasmid-mediated bla NDM-1 and aac(6')-Ib-cr
      genes was performed. DNA was purified from the OMVs and used for PCR and dot-blot
      analysis. Vesicles treated with DNase I and proteinase K were used to transform
      A. baumannii ATCC 19606 and Escherichia coli JM109 strains. MIC values for the
      transformants were determined, followed by PCR and restriction digestion of
      plasmids. PFGE was done for A_115 and transformants of ATCC 19606 and JM109.
      Results: The A. baumannii strain (ST 1462) released vesicles (25-100 nm) during
      in vitro growth at late log phase. PCR and dot-blot analysis confirmed the
      presence of bla NDM-1 and aac(6')-Ib-cr genes in intravesicular DNA. bla NDM-1
      and aac(6')-Ib-cr genes were transferred to both the A. baumannii ATCC 19606 and
      E. coli JM109 recipient cells. The transformation frequency of the purified OMVs
      was in the range of 10 -5 -10 -6 and gradually reduced with storage of OMVs. The
      sizes of the plasmids in the transformants and their restriction digestion
      patterns were identical to the plasmid in A_115. The transformants showed
      elevated MIC values of the beta-lactam group of antibiotics, which confirmed the
      presence of a bla NDM-1 -harbouring plasmid. Conclusions: This is the first
      experimental evidence of intra- and inter-species transfer of a plasmid
      harbouring a bla NDM-1 gene in A. baumannii via OMVs with high transformation
      frequency.

PMID- 28505328
TI  - Advanced Human Immunodeficiency Virus Disease in Botswana Following Successful
      Antiretroviral Therapy Rollout: Incidence of and Temporal Trends in Cryptococcal
      Meningitis.
AB  - Background: Botswana has a well-developed antiretroviral therapy (ART) program
      that serves as a regional model. With wide ART availability, the burden of
      advanced human immunodeficiency virus (HIV) and associated opportunistic
      infections would be expected to decline. We performed a nationwide surveillance
      study to determine the national incidence of cryptococcal meningitis (CM), and
      describe characteristics of cases during 2000-2014 and temporal trends at 2
      national referral hospitals. Methods: Cerebrospinal fluid data from all 37
      laboratories performing meningitis diagnostics in Botswana were collected from
      the period 2000-2014 to identify cases of CM. Basic demographic and laboratory
      data were recorded. Complete national data from 2013-2014 were used to calculate
      national incidence using UNAIDS population estimates. Temporal trends in cases
      were derived from national referral centers in the period 2004-2014. Results: A
      total of 5296 episodes of CM were observed in 4702 individuals; 60.6% were male,
      and median age was 36 years. Overall 2013-2014 incidence was 17.8 (95% confidence
      interval [CI], 16.6-19.2) cases per 100000 person-years. In the HIV-infected
      population, incidence was 96.8 (95% CI, 90.0-104.0) cases per 100000 person
      years; male predominance was seen across CD4 strata. At national referral
      hospitals, cases decreased during 2007-2009 but stabilized during 2010-2014.
      Conclusions: Despite excellent ART coverage in Botswana, there is still a
      substantial burden of advanced HIV, with 2013-2014 incidence of CM comparable to
      pre-ART era rates in South Africa. Our findings suggest that a key population of
      individuals, often men, is developing advanced disease and associated
      opportunistic infections due to a failure to effectively engage in care,
      highlighting the need for differentiated care models.

PMID- 28505331
TI  - Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to
      alternative antimicrobials with therapeutic potential.
AB  - Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally
      and represents a public health emergency. Development and approval of new anti
      gonococcal agents may take years. As a concurrent approach to developing new
      antimicrobials, the laboratory and clinical evaluation of currently licensed
      antimicrobials not widely used for the treatment of gonorrhoea may provide new
      options for the treatment of gonococcal infections. Objectives: To determine the
      in vitro activity of nine alternative, currently licensed and late-development
      antimicrobials with the potential to treat gonococcal infections against 112
      clinical isolates of N. gonorrhoeae resistant to one or multiple antimicrobials.
      Methods: The MICs of conventional anti-gonococcal antimicrobials (penicillin,
      ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline and
      spectinomycin) and alternative antimicrobials (ertapenem, gentamicin, netilmicin,
      tigecycline, eravacycline, fosfomycin, linezolid, ceftazidime/avibactam and
      ceftaroline) were determined by agar dilution. Results: Ertapenem and the novel
      cephalosporins demonstrated similar MIC values to the third-generation
      cephalosporins, but increased MICs were observed for isolates with increased
      cefixime and ceftriaxone MICs. Tigecycline and eravacycline had MIC values below
      expected serum concentrations for all isolates tested. The aminoglycosides
      gentamicin and netilmicin were generally more potent than spectinomycin, with
      netilmicin demonstrating the greatest potency. Fosfomycin MICs were elevated
      compared with other agents, but remained within the MIC range for susceptible
      organisms, while linezolid MICs were generally higher than those for organisms
      considered resistant. Conclusions: Among potentially therapeutically useful
      alternative agents, the aminoglycosides, eravacycline, tigecycline and fosfomycin
      had good in vitro activity. The novel cephalosporins and ertapenem had comparable
      activity to cefixime and ceftriaxone.

PMID- 28505332
TI  - A Comparative Benchmark Dose Study for N, N-Dimethylformamide Induced Liver
      Injury in a Chinese Occupational Cohort.
AB  - Widespread contamination of N,N-dimethylformamide (DMF) has been identified in
      the environment of leather industries and their surrounding residential areas.
      Few studies have assessed the dose-response relationships between internal
      exposure biomarkers and liver injury in DMF exposed populations. We assessed
      urinary N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl) cysteine
      (AMCC) and blood N-methylcarbmoylated hemoglobin (NMHb) levels in 698 Chinese DMF
      exposed workers and 188 nonDMF- exposed workers using ultraperformance liquid
      chromatography tandem mass-spectrometry. Liver injury was defined as having
      abnormal serum activities of any of the 3 liver enzymes, including alanine
      aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase.
      Higher liver injury rates were identified in DMF-exposed workers versus nonDMF
      exposed workers (9.17% vs 4.26%, P = .029) and in male versus female workers
      (11.4% vs 3.2%, P < .001). Positive correlations between environmental exposure
      categories and internal biomarker levels were identified with all 3 biomarkers
      undetectable in nonDMF-exposed workers. Lower confidence limit of benchmark dose
      (BMDL) was estimated using the benchmark dose (BMD) method. Within all study
      subjects, BMDLs of 14.0 mg/l for NMF, 155 mg/l for AMCC, and 93.3 nmol/g for NMHb
      were estimated based on dose-response relationships between internal levels and
      liver injury rates. Among male workers, BMDLs of 10.9 mg/l for NMF, 119 mg/l for
      AMCC, and 97.0 nmol/g for NMHb were estimated. In conclusion, NMF, AMCC, and NMHb
      are specific and reliable biomarkers and correlate well with DMF-induced
      hepatotoxicity. NMF correlates the best with liver injury, while NMHb may be the
      most stable indicator. Males have a greater risk of liver injury than females
      upon DMF exposure.

PMID- 28505334
TI  - DIRECTION: a machine learning framework for predicting and characterizing DNA
      methylation and hydroxymethylation in mammalian genomes.
AB  - Motivation: 5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major
      epigenetic modifications known to significantly alter mammalian gene expression.
      High-throughput assays to detect these modifications are expensive, labor
      intensive, unfeasible in some contexts and leave a portion of the genome
      unqueried. Hence, we devised a novel, supervised, integrative learning framework
      to perform whole-genome methylation and hydroxymethylation predictions in CpG
      dinucleotides. Our framework can also perform imputation of missing or low
      quality data in existing sequencing datasets. Additionally, we developed
      infrastructure to perform in silico, high-throughput hypotheses testing on such
      predicted methylation or hydroxymethylation maps. Results: We test our approach
      on H1 human embryonic stem cells and H1-derived neural progenitor cells. Our
      predictive model is comparable in accuracy to other state-of-the-art DNA
      methylation prediction algorithms. We are the first to predict hydroxymethylation
      in silico with high whole-genome accuracy, paving the way for large-scale
      reconstruction of hydroxymethylation maps in mammalian model systems. We designed
      a novel, beam-search driven feature selection algorithm to identify the most
      discriminative predictor variables, and developed a platform for performing
      integrative analysis and reconstruction of the epigenome. Our toolkit DIRECTION
      provides predictions at single nucleotide resolution and identifies relevant
      features based on resource availability. This offers enhanced biological
      interpretability of results potentially leading to a better understanding of
      epigenetic gene regulation. Availability and implementation:
      http://www.pradiptaray.com/direction, under CC-by-SA license. Contacts:
      pradiptaray@gmail.com or mchen@utdallas.edu or michael.zhang@utdallas.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28505335
TI  - Functional analysis of novel RUNX2 mutations in cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal disorder
      caused by mutation of runt-related transcription factor 2 (RUNX2) gene. The
      purpose of this study was to explore novel RUNX2 mutations in seven individuals
      with CCD and investigate the function of the mutant RUNX2 proteins. DNA samples
      were prepared from the peripheral blood of the CCD individuals, and then
      subjected to DNA sequencing. Conservation and secondary structure analysis were
      performed based on RUNX2 sequencing results. pEGFP-C1 plasmids containing GFP
      tagged wild-type RUNX2 and three novel RUNX2 mutations expression cassettes were
      constructed, and then transfected into HEK293T cells. Cell fluorescence,
      luciferase assay and western blotting were used to analyse the subcellular
      distribution and function of the mutant RUNX2 proteins. Three novel mutations
      (R193G, 258fs, Y400X) were found in the seven CCD patients. Conservation and
      structure analysis show one novel mutation (R193G) in Runt domain and two novel
      mutations (258fs and Y400X) in PST domain of RUNX2. Western blotting confirmed
      that the 258fs and Y400X mutations produced truncated proteins. Fluorescence
      detection showed that the three novel mutants localised exclusively in the
      nucleus. However, luciferase assay indicated all mutants severely impaired the
      transactivation activities of RUNX2 on osteocalcin promoter. Our results broaden
      the spectrum of RUNX2 mutations in CCD individuals and demonstrated that loss of
      function in RUNX2 is responsible for CCD.

PMID- 28505336
TI  - Financial Capacity and its Cognitive Predictors in Progressive Multiple
      Sclerosis.
AB  - Objective: Financial capacity is a cognitively-complex activity of daily living
      that has been shown to decline in a number of neurocognitive disorders. Although
      it has been well established that cognitive decline is common in multiple
      sclerosis (MS), little is known about possible financial capacity impairment in
      people with MS. Thus, the objective of the current study is to investigate
      financial capacity and its neurocognitive correlates in MS. Methods: Data from 22
      people with progressive MS and a healthy comparison group composed of 18 adults
      were analyzed. MS diagnoses were made by a board-certified neurologist with
      experience in MS. Study participants were administered the Financial Capacity
      Instrument, a performance-based measure of financial capacity, and
      neuropsychological battery. Results: Overall financial capacity and most complex
      financial domains were significantly poorer for people with progressive MS in
      relation to the healthy comparison group, and a number of cognitive variables
      were associated with financial capacity declines. Conclusions: Financial capacity
      is a complex cognitively-mediated functional ability that was impaired in 50% of
      the current sample of people with progressive MS. These results indicate that
      people with progressive MS are at greater risk for showing impairment in complex
      financial tasks and should be clinically monitored for possible deficits in
      financial capacity.

PMID- 28505333
TI  - Multiregional Age-Associated Reduction of Brain Neuronal Reserve Without
      Association With Neurofibrillary Degeneration or beta-Amyloidosis.
AB  - Increase in human life expectancy has resulted in the rapid growth of the elderly
      population with minimal or no intellectual deterioration. The aim of this
      stereological study of 10 structures and 5 subdivisions with and without
      neurofibrillary degeneration in the brains of 28 individuals 25-102-years-old was
      to establish the pattern of age-associated neurodegeneration and neuronal loss in
      the brains of nondemented adults and elderly. The study revealed the absence of
      significant neuronal loss in 7 regions and topographically selective reduction of
      neuronal reserve over 77 years in 8 brain structures including the entorhinal
      cortex (EC) (-33.3%), the second layer of the EC (-54%), cornu Ammonis sector 1
      (CA1) (-28.5%), amygdala, (-45.8%), thalamus (-40.5%), caudate nucleus (-35%),
      Purkinje cells (-48.3%), and neurons in the dentate nucleus (40.1%). A similar
      rate of neuronal loss in adults and elderly, without signs of accelerating
      neuronal loss in agers or super-agers, appears to indicate age-associated brain
      remodeling with significant reduction of neuronal reserve in 8 brain regions.
      Multivariate analysis demonstrates the absence of a significant association
      between neuronal loss and the severity of neurofibrillary degeneration and beta
      amyloidosis, and a similar rate of age-associated neuronal loss in structures
      with and without neurofibrillary degeneration.

PMID- 28505337
TI  - Sex Differences in Brain Regions Modulating Pain Among Older Adults: A Cross
      Sectional Resting State Functional Connectivity Study.
AB  - Objective: A long-standing hypothesis is that when compared with males, females
      may be at increased risk of experiencing greater pain sensitivity and
      unpleasantness. The purpose of this study was to examine sex differences in pain
      psychophysics and resting state functional connectivity (RSFC) in core pain
      regions in an age- and sex-matched sample of healthy older adults. Design:
      Between groups, cross-sectional. Setting: Vanderbilt University and Medical
      Center. Subjects: The sample in the analyses reported here consisted of 19
      cognitively intact males matched with 19 cognitively intact females of similar
      ages (median ages: females = 70 years, males = 68 years). Methods: Psychophysical
      assessment of experimental thermal pain and RSFC. Results: There were no
      significant differences in perceptual thresholds or unpleasantness ratings in
      response to thermal stimuli. Older males showed greater RSFC between the
      affective and sensory networks and between affective and descending modulatory
      networks. Conversely, older females showed greater RSFC between the descending
      modulatory network and both sensory and affective networks. The strongest
      evidence for sex differences emerged in the associations of thermal pain with
      RSFC between the anterior cingulate cortex (ACC) and amygdala and between the ACC
      and periaqueductal gray matter in older females relative to older males.
      Conclusions: We found no differences in pain sensitivity or pain affect between
      older males and older females. Additionally, we found that older females
      exhibited a greater association between thermal pain sensitivity and RSFC signal
      between regions typically associated with pain affect and the descending
      modulatory system. One interpretation of these findings is that older females may
      better engage the descending pain modulatory system. This better engagement
      possibly translates into older females having similar perceptual thresholds for
      temperature sensitivity and unpleasantness associated with mild and moderate
      pain. These findings contrast with studies demonstrating that younger females
      find thermal pain more sensitive and more unpleasant.

PMID- 28505338
TI  - Concordance Between Anal and Oral Human Papillomavirus Infections Among Young Men
      Who have Sex With Men.
AB  - Prevalence of human papillomavirus (HPV) infections was assessed among 1033 young
      men who have sex with men (MSM) aged 18-26 years. HPV (any type) was detected in
      742 (71.8%) anal specimens and 101 (9.8%) oral specimens. Although HPV was
      detected in specimens from both anatomical sites in 83 (8.0%) participants, type
      specific concordance for at least 1 HPV type was found in only 35 (3.4%)
      participants. HIV and smoking were associated with higher prevalence at both
      sites and frequency of concordant types. Coinfections of identical HPV types were
      rare, suggesting independent infection events and/or different modes of
      clearance.

PMID- 28505339
TI  - LabRS: A Rosetta stone for retrospective standardization of clinical laboratory
      test results.
AB  - Objective: Clinical laboratories in the United States do not have an explicit
      result standard to report the 7 billion laboratory tests results they produce
      each year. The absence of standardized test results creates inefficiencies and
      ambiguities for secondary data users. We developed and tested a tool to
      standardize the results of laboratory tests in a large, multicenter clinical data
      warehouse. Methods: Laboratory records, each of which consisted of a laboratory
      result and a test identifier, from 27 diverse facilities were captured from 2000
      through 2015. Each record underwent a standardization process to convert the
      original result into a format amenable to secondary data analysis. The
      standardization process included the correction of typos, normalization of
      categorical results, separation of inequalities from numbers, and conversion of
      numbers represented by words (eg, "million") to numerals. Quality control
      included expert review. Results: We obtained 1.266 * 109 laboratory records and
      standardized 1.252 * 109 records (98.9%). Of the unique unstandardized records
      (78.887 * 103), most appeared <5 times (96%, eg, typos), did not have a test
      identifier (47%), or belonged to an esoteric test with <100 results (2%).
      Overall, these 3 reasons accounted for nearly all unstandardized results (98%).
      Conclusion: Current results suggest that the tool is both scalable and
      generalizable among diverse clinical laboratories. Based on observed trends, the
      tool will require ongoing maintenance to stay current with new tests and result
      formats. Future work to develop and implement an explicit standard for test
      results would reduce the need to retrospectively standardize test results.

PMID- 28505340
TI  - Members of Microvirga and Bradyrhizobium genera are native endosymbiotic bacteria
      nodulating Lupinus luteus in Northern Tunisian soils.
AB  - The genetic diversity of bacterial populations nodulating Lupinus luteus (yellow
      lupine) in Northern Tunisia was examined. Phylogenetic analyses of 43 isolates
      based on recA and gyrB partial sequences grouped them in three clusters, two of
      which belong to genus Bradyrhizobium (41 isolates) and one, remarkably, to
      Microvirga (2 isolates), a genus never previously described as microsymbiont of
      this lupine species. Representatives of the three clusters were analysed in-depth
      by multilocus sequence analysis of five housekeeping genes (rrs, recA, glnII,
      gyrB and dnaK). Surprisingly, the Bradyrhizobium cluster with the two isolates
      LluI4 and LluTb2 may constitute a new species defined by a separate position
      between Bradyrhizobium manausense and B. denitrificans. A nodC-based phylogeny
      identified only two groups: one formed by Bradyrhizobium strains included in the
      symbiovar genistearum and the other by the Microvirga strains. Symbiotic
      behaviour of representative isolates was tested, and among the seven legumes
      inoculated only a difference was observed i.e. the Bradyrhizobium strains
      nodulated Ornithopus compressus unlike the two strains of Microvirga. On the
      basis of these data, we conclude that L. luteus root nodule symbionts in Northern
      Tunisia are mostly strains within the B. canariense/B. lupini lineages, and the
      remaining strains belong to two groups not previously identified as L. luteus
      endosymbionts: one corresponding to a new clade of Bradyrhizobium and the other
      to the genus Microvirga.

PMID- 28505342
TI  - Letter to the Editor: Author Response - Analysis of Rhizome Development in Oryza
      longistaminata, a Wild Rice Species.

PMID- 28505341
TI  - Association of Changes in Neighborhood-Level Racial Residential Segregation With
      Changes in Blood Pressure Among Black Adults: The CARDIA Study.
AB  - Importance: Despite cross-sectional evidence linking racial residential
      segregation to hypertension prevalence among non-Hispanic blacks, it remains
      unclear how changes in exposure to neighborhood segregation may be associated
      with changes in blood pressure. Objective: To examine the association of changes
      in neighborhood-level racial residential segregation with changes in systolic and
      diastolic blood pressure over a 25-year period. Design, Setting, and
      Participants: This observational study examined longitudinal data of 2280 black
      participants of the Coronary Artery Risk Development in Young Adults (CARDIA)
      study, a prospective investigation of adults aged 18 to 30 years who underwent
      baseline examinations in field centers in 4 US locations from March 25, 1985, to
      June 7, 1986, and then were re-examined for the next 25 years. Racial residential
      segregation was assessed using the Getis-Ord Gi* statistic, a measure of SD
      between the neighborhood's racial composition (ie, percentage of black residents)
      and the surrounding area's racial composition. Segregation was categorized as
      high (Gi* >1.96), medium (Gi* 0-1.96), and low (Gi* <0). Fixed-effects linear
      regression modeling was used to estimate the associations of within-person change
      in exposure to segregation and within-person change in blood pressure while
      tightly controlling for time-invariant confounders. Data analyses were performed
      between August 4, 2016, and February 9, 2017. Main Outcomes and Measures: Within
      person changes in systolic and diastolic blood pressure across 6 examinations
      over 25 years. Results: Of the 2280 participants at baseline, 974 (42.7%) were
      men and 1306 (57.3%) were women. Of these, 1861 (81.6%) were living in a high
      segregation neighborhood; 278 (12.2%), a medium-segregation neighborhood; and 141
      (6.2%), a low-segregation neighborhood. Systolic blood pressure increased by a
      mean of 0.16 (95% CI, 0.06-0.26) mm Hg with each 1-SD increase in segregation
      score after adjusting for interactions of time with age, sex, and field center.
      Of the 1861 participants (81.6%) who lived in high-segregation neighborhoods at
      baseline, reductions in exposure to segregation were associated with reductions
      in systolic blood pressure. Mean differences in systolic blood pressure were 
      1.33 (95% CI, -2.26 to -0.40) mm Hg when comparing high-segregation with medium
      segregation neighborhoods and -1.19 (95% CI, -2.08 to -0.31) mm Hg when comparing
      high-segregation with low-segregation neighborhoods after adjustment for time and
      interactions of time with baseline age, sex, and field center. Changes in
      segregation were not associated with changes in diastolic blood pressure.
      Conclusions and Relevance: Decreases in exposure to racial residential
      segregation are associated with reductions in systolic blood pressure. This study
      adds to the small but growing body of evidence that policies that reduce
      segregation may have meaningful health benefits.

PMID- 28505343
TI  - Training issues in ultrasound and the benefits of an International Fellowship.

PMID- 28505345
TI  - Cardio-oncology: a multidisciplinary approach for detection, prevention and
      management of cardiac dysfunction in cancer patients.
AB  - Cardiac dysfunction that develops during or after completion of cancer therapy is
      a growing health concern that should be addressed in a multidisciplinary setting.
      Cardio-oncology is a new discipline that focuses on screening, monitoring and
      treating cardiovascular disease during and after cancer treatment. A baseline
      cardiovascular risk assessment is essential. For high-risk patients, a tailored
      and detailed plan for cardiovascular management throughout treatment and beyond
      should also be established. Anthracycline and/or trastuzumab-containing
      chemotherapy and chest-directed radiation therapy are well known cardiotoxic
      cancer therapies. Monitoring for the development of subclinical cardiotoxicity is
      crucial for the prevention of clinical heart failure. Detecting a decreased left
      ventricular ejection fraction after cancer therapy might be a late finding;
      therefore, earlier markers of cardiac injury are being actively explored.
      Abnormal myocardial strain and increased serum cardiac biomarkers (e.g. troponins
      and natriuretic peptides) are possible candidates for this purpose. An important
      method for preventing heart failure is the avoidance or minimization of the use
      of cardiotoxic therapies. Decisions must balance the anti-tumor efficacy of the
      treatment with its potential cardiotoxicity. If patients develop cardiac
      dysfunction or heart failure, they should be treated in accordance with
      established guidelines for heart failure. Cancer survivors who have been exposed
      to cardiotoxic cancer therapies are at high risk of developing heart failure. The
      management of cardiovascular risk factors and periodic screening with cardiac
      imaging and biomarkers should be considered in high-risk survivors.

PMID- 28505346
TI  - Breast cancer screening (BCS) chart: a basic and preliminary model for making
      screening mammography more productive and efficient.
AB  - BACKGROUND: The breast cancer screening (BCS) chart is suggested as a basic and
      preliminary tool to improve efficiency of screening mammography. METHODS: We
      conducted this case-control study in 2016 and enrolled 1422 women aged 30-75
      years, including 506 women with breast cancer (cases) and 916 women without
      breast cancer (controls). We developed the BCS chart using a multiple logistic
      regression analysis. We combined the risks of breast cancer to predict the
      individual risk of breast cancer. Then, we stratified and colored the predicted
      risk probabilities as follows: <05% (green), 05-09% (yellow), 10-14% (orange), 15
      19% (red), 20-24% (brown) and >=25% (black). RESULTS: The BCS chart provides the
      risk probability of breast cancer, based on age, body mass index, late menopause,
      having a benign breast disease and a positive family history of breast cancer
      among the first-degree or the second/third-degree relatives. According to this
      chart, an individual can be classified in a category of low risk (green), medium
      risk (yellow and orange), high risk (red and brown) and very high risk (black)
      for breast cancer. CONCLUSIONS: This chart is a flexible and easy to use tool
      that can detect high-risk subjects and make the screening program more efficient
      and productive.

PMID- 28505347
TI  - Body-weight and psychological well-being in the UK general population.
AB  - Background: While the consequences of body weight for physical health are well
      explored, the evidence for psychological well-being is less straightforward. An
      instrumental variable approach is used to address the endogenous relationship
      between body weight and well-being in the UK general population. Methods: Data
      from the Health Survey for England (2003, 2004 and 2006) are used to fit linear
      and ordered probit instrument variable models for a sample of 13 862 individuals,
      with frequent white meat consumption instrumenting for body-weight. Non
      linearities in the relationship, robustness to weak instruments and relaxation of
      strict exogeneity assumption are further examined. Results: Accounting for
      endogeneity and conditional on health a protective effect on well-being is
      observed. A unit increase in body mass index (BMI) improves General Health
      Questionnaire (GHQ) by 0.17 (95% CI: 0.02-0.31) points and reduces the
      probability of reporting very low GHQ by 2.5% (95% CI: 0.01-0.05). Empirical
      testing showed that the instrument performs well, with increased meat consumption
      adding 0.58 points (95% CI: 0.42-0.74) to ones' BMI. Conclusions: We present
      support for the jolly-fat hypothesis, however, caution is recommended in drawing
      inferences. Further research needs to resolve the mixed findings in the
      literature.

PMID- 28505344
TI  - Genetics of glaucoma.
AB  - Genetic and genomic studies, including genome-wide association studies (GWAS)
      have accelerated the discovery of genes contributing to glaucoma, the leading
      cause of irreversible blindness world-wide. Glaucoma can occur at all ages, with
      Mendelian inheritance typical for the rare early onset disease (before age 40)
      and complex inheritance evident in common adult-onset forms of disease. Recent
      studies have suggested possible therapeutic targets for some patients with early
      onset glaucoma based on the molecular and cellular events caused by MYOC, OPTN
      and TBK1 mutations. Diagnostic genetic tests using early-onset glaucoma genes are
      also proving useful for pre-symptomatic disease detection and genetic counseling.
      Recent GWAS completed for three types of common adult-onset glaucoma have
      identified novel loci for POAG (primary-open-angle glaucoma) (ABCA1, AFAP1, GMDS,
      PMM2, TGFBR3, FNDC3B, ARHGEF12, GAS7, FOXC1, ATXN2, TXNRD2); PACG (primary angle
      closure glaucoma (EPDR1, CHAT, GLIS3, FERMT2, DPM2-FAM102); and exfoliation
      syndrome (XFS) glaucoma (CACNA1A). In total sixteen genomic regions have been
      associated with POAG (including the normal tension glaucoma (NTG) subgroup), 8
      with PACG and 2 with XFS. These studies are defining important biological
      pathways and processes that contribute to disease pathogenesis.

PMID- 28505350
TI  - Evidence of Altered Trigeminal Nociception in an Animal Model of Fibromyalgia.
AB  - Objective: Fibromyalgia (FM) is a debilitating chronic condition that
      significantly affects quality of life. A strong association has been demonstrated
      between FM and chronic pain in the trigeminal region in clinical studies. This
      study was performed to evaluate the response to acute and chronic noxious stimuli
      applied to the facial region. Methods: Adult male Wistar rats (250-270 g, N = 10
      for each group) were used in the current study. A subchronic swim stress model
      was used as the animal model of FM. Anxiety-like behaviors and response to acute
      and chronic noxious stimuli were assayed using the elevated plus maze, eye wiping
      test, and orofacial formalin test, respectively. Balance and motor function were
      evaluated using rotarod and wire grip tests. Results: An increased anxiety-like
      behavior was observed in swim stress rats in comparison with control and sham
      subjects. Response to acute and chronic noxious stimuli in the trigeminal region
      was increased in the stressed rats. Motor and balance function were not altered
      following stress. Conclusions: Results of the current study demonstrated a
      hyperalgesic state in the trigeminal region in a possible animal model of FM.
      This study provides a reliable animal model for further research on the possible
      mechanisms of orofacial pain in FM.

PMID- 28505349
TI  - Decline of Ecological Functions Performed by Dung Beetles in Areas of Atlantic
      Forest and Contribution of Rollers and Tunnellers in Organic Matter Removal.
AB  - The feeding behavior of the Scarabaeinae subfamily has positive implications on
      ecosystem functioning. We characterize the necrophagous and coprophagous dung
      beetle assemblages, and we quantify the removal of swine carrion and domestic dog
      dung in two areas with different degrees of environmental disturbance in an
      Atlantic Forest remnant located in Florianopolis, SC, Brazil. The experiment was
      setup at eight sampling points in each area, by installing one control and two
      collection and removal assessment arenas for collecting necrophagous dung beetles
      while simultaneously evaluating the removal of carrion (50 g of rotting pork for
      48 h). We used the same sample design with 50 g of domestic dog dung for
      evaluating the coprophagous dung beetle assemblage and dung removal. Our results
      indicated that necrophagous dung beetles were more sensitive to environmental
      disturbance owing to a lower richness and changes in species dominance, which
      resulted in a lower removal in the areas with greater disturbance and lower
      environmental quality (39.6% carrion removal) in relation to less disturbed areas
      (75.1% carrion removal). The dung beetle assemblages were similar in structure
      and removal rates between areas (80% of dung was removed). In assessing the
      influence of richness, abundance, and biomass of dung beetles on resource removal
      both for the whole assemblage and for each separate functional guild, only the
      abundance and biomass of rollers contributed significantly to dung removal. These
      results highlight the implications of environmental disturbances on the functions
      of dung beetles, which respond differently according to the resource they use.

PMID- 28505348
TI  - Implication of the box C/D snoRNP assembly factor Rsa1p in U3 snoRNP assembly.
AB  - The U3 box C/D snoRNA is one key element of 90S pre-ribosome. It contains a 5?
      domain pairing with pre-rRNA and the U3B/C and U3C?/D motifs for U3 packaging
      into a unique small nucleolar ribonucleoprotein particle (snoRNP). The RNA
      binding protein Snu13/SNU13 nucleates on U3B/C the assembly of box C/D proteins
      Nop1p/FBL and Nop56p/NOP56, and the U3-specific protein Rrp9p/U3-55K.
      Snu13p/SNU13 has a much lower affinity for U3C?/D but nevertheless forms on this
      motif an RNP with box C/D proteins Nop1p/FBL and Nop58p/NOP58. In this study, we
      characterized the influence of the RNP assembly protein Rsa1 in the early steps
      of U3 snoRNP biogenesis in yeast and we propose a refined model of U3 snoRNP
      biogenesis. While recombinant Snu13p enhances the binding of Rrp9p to U3B/C, we
      observed that Rsa1p has no effect on this activity but forms with Snu13p and
      Rrp9p a U3B/C pre-RNP. In contrast, we found that Rsa1p enhances Snu13p binding
      on U3C?/D. RNA footprinting experiments indicate that this positive effect most
      likely occurs by direct contacts of Rsa1p with the U3 snoRNA 5? domain. In light
      of the recent U3 snoRNP cryo-EM structures, our data suggest that Rsa1p has a
      dual role by also preventing formation of a pre-mature functional U3 RNP.

PMID- 28505351
TI  - Centre effects and peritoneal dialysis-related peritonitis.

PMID- 28505352
TI  - The Nodulin 26-like intrinsic membrane protein OsNIP3;2 is involved in arsenite
      uptake by lateral roots in rice.
AB  - Previous studies have shown that the Nodulin 26-like intrinsic membrane protein
      (NIP) Lsi1 (OsNIP2;1) is involved in arsenite [As(III)] uptake in rice (Oryza
      sativa). However, the role of other rice NIPs in As(III) accumulation in planta
      remains unknown. In the present study, we investigated the role OsNIP3;2 in
      As(III) uptake in rice. When expressed in Xenopus laevis oocytes, OsNIP3;2 showed
      a high transport activity for As(III). Quantitative real-time RT-PCR showed that
      the expression of OsNIP3;2 was suppressed by 5 uM As(III), but enhanced by 20 and
      100 uM As(III). Transgenic rice plants expressing OsNIP3;2pro-GUS showed that the
      gene was predominantly expressed in the lateral roots and the stele region of the
      primary roots. Transient expression of OsNIP3;2:GFP fusion protein in rice
      protoplasts showed that the protein was localized in the plasma membrane.
      Knockout of OsNIP3;2 significantly decreased As concentration in the roots, but
      had little effect on shoot As concentration. Synchrotron microfocus X-ray
      fluorescence showed decreased As accumulation in the stele of the lateral roots
      in the mutants compared with wild-type. Our results indicate that OsNIP3;2 is
      involved in As(III) uptake by lateral roots, but its contribution to As
      accumulation in the shoots is limited.

PMID- 28505353
TI  - Co-occurrence of mcr-1 and blaKPC-2 in a clinical isolate of Escherichia coli in
      Brazil.

PMID- 28505354
TI  - Psychological distress in men with prostate cancer and their partners before and
      after cancer diagnosis: a longitudinal study.
AB  - Objective: To examine the relative risk of psychological distress of men with
      prostate cancer and their partners during the period before and after prostate
      cancer diagnosis compared with men without prostate cancer and their partners.
      Methods: The participants reported questionnaires on psychological distress at
      four time points: before prostate cancer biopsy, and at 1, 3 and 6 months
      following prostate cancer diagnosis. We performed multiple logistic regression
      analyses to examine the relative risk of psychological distress. Results: A total
      of 115 couples answered the questionnaires at all four time points. Men with
      prostate cancer showed a significantly higher risk of psychological distress
      compared to men without prostate cancer at 1 (odds ratio [OR] = 4.8, 95%
      confidence interval [CI] = 1.9-13.1), 3 (OR = 3.2, 95% CI = 1.1-10.2) and 6
      months following prostate cancer diagnosis (OR = 6.9, 95% CI = 2.3-25.7). Their
      partners showed a significantly higher risk of psychological distress compared to
      the partners of men without prostate cancer at 1 month following prostate cancer
      diagnosis (OR = 2.6, 95% CI = 1.1-6.6). Conclusions: Men with prostate cancer
      showed psychological distress during the 6 months following the cancer diagnosis.
      Their partners also showed psychological distress at 1 month following the cancer
      diagnosis. Inviting both men with prostate cancer and their partners to speak to
      their concerns, empathizing with them, finding the solutions together and
      monitoring of their psychological status regularly should be regarded as
      important following prostate cancer diagnosis.

PMID- 28505357
TI  - Resilience and Vulnerability Factors When Pain is Acute as Predictors of
      Disability: Findings From a Two-Year Longitudinal Study.
AB  - Objective: To investigate the predictive power of resilience and vulnerability
      factors in relation to pain-related disability. Design: A two-year prospective
      study investigated whether back pain-related disability was predicted by the
      following variables, measured when pain was acute: 1) pain-related disability, 2)
      pain intensity, 3) depression, 4) fear avoidance beliefs, 5) anxiety sensitivity,
      and 6) resilience. Methods: Two hundred thirty-two patients treated in five
      primary care centers participated in this study. They were assessed at baseline
      during an acute back pain episode and at six, 12, 18, and 24 months. Ninety-nine
      patients completed all the assessment sessions. Linear mixed models were used to
      examine the trajectory of disability across the measurement occasions and its
      association with the predictors. Results: Individuals who had higher scores of
      disability and pain intensity when pain was acute also had higher scores of
      disability six months later; moreover, the increase in disability was greater
      over time in comparison with individuals with lower scores in disability and pain
      intensity when pain was acute. Individuals who had reported greater levels of
      fear avoidance beliefs when pain was acute also reported greater scores of
      disability six months later; however, no differences were found in the rate of
      change in disability. No associations were found between initial disability or
      rate of change and resilience, anxiety sensitivity, or depression. Conclusions:
      Patients with acute back pain who show high levels of pain-related disability,
      pain intensity, and fear avoidance beliefs are at risk of developing back pain
      related disability and should be the target of a preventive intervention.

PMID- 28505355
TI  - Uncovering the neuroanatomical correlates of cognitive, affective and conative
      theory of mind in paediatric traumatic brain injury: a neural systems
      perspective.
AB  - Deficits in theory of mind (ToM) are common after neurological insult acquired in
      the first and second decade of life, however the contribution of large-scale
      neural networks to ToM deficits in children with brain injury is unclear. Using
      paediatric traumatic brain injury (TBI) as a model, this study investigated the
      sub-acute effect of paediatric traumatic brain injury on grey-matter volume of
      three large-scale, domain-general brain networks (the Default Mode Network, DMN;
      the Central Executive Network, CEN; and the Salience Network, SN), as well as two
      domain-specific neural networks implicated in social-affective processes (the
      Cerebro-Cerebellar Mentalizing Network, CCMN and the Mirror Neuron/Empathy
      Network, MNEN). We also evaluated prospective structure-function relationships
      between these large-scale neural networks and cognitive, affective and conative
      ToM. 3D T1- weighted magnetic resonance imaging sequences were acquired sub
      acutely in 137 children [TBI: n = 103; typically developing (TD) children: n =
      34]. All children were assessed on measures of ToM at 24-months post-injury.
      Children with severe TBI showed sub-acute volumetric reductions in the CCMN, SN,
      MNEN, CEN and DMN, as well as reduced grey-matter volumes of several hub regions
      of these neural networks. Volumetric reductions in the CCMN and several of its
      hub regions, including the cerebellum, predicted poorer cognitive ToM. In
      contrast, poorer affective and conative ToM were predicted by volumetric
      reductions in the SN and MNEN, respectively. Overall, results suggest that
      cognitive, affective and conative ToM may be prospectively predicted by
      individual differences in structure of different neural systems-the CCMN, SN and
      MNEN, respectively. The prospective relationship between cerebellar volume and
      cognitive ToM outcomes is a novel finding in our paediatric brain injury sample
      and suggests that the cerebellum may play a role in the neural networks important
      for ToM. These findings are discussed in relation to neurocognitive models of
      ToM. We conclude that detection of sub-acute volumetric abnormalities of large
      scale neural networks and their hub regions may aid in the early identification
      of children at risk for chronic social-cognitive impairment.

PMID- 28505356
TI  - Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection
      and Risk in RTS,S/AS01E Vaccinees.
AB  - Background: The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in
      infants than children. Current efforts to enhance RTS,S/AS01E efficacy would
      benefit from learning about the vaccine-induced immunity and identifying
      correlates of malaria protection, which could, for instance, inform the choice of
      adjuvants. Here, we sought cellular immunity-based correlates of malaria
      protection and risk associated with RTS,S/AS01E vaccination. Methods: We
      performed a matched case-control study nested within the multicenter African
      RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria
      cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106
      RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex
      following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization.
      Crude concentrations and ratios of antigen to background control were analyzed.
      Results: Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E
      vaccination (adjusted P <= .01). IL-5 circumsporozoite protein (CSP) ratios, a
      helper T cell type 2 cytokine, correlated with higher odds of malaria in
      RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value
      adjusted for multiple testing = .03). In multimarker analysis, the helper T cell
      type 1 (TH1)-related markers interferon-gamma, IL-15, and granulocyte-macrophage
      colony-stimulating factor protected from subsequent malaria, in contrast to IL-5
      and RANTES, which increased the odds of malaria. Conclusions: RTS,S/AS01E-induced
      IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may
      be involved in protective mechanisms. Efforts to develop second-generation
      vaccine candidates may concentrate on adjuvants that modulate the immune system
      to support enhanced TH1 responses and decreased IL-5 responses.

PMID- 28505358
TI  - Hijab and Depression: Does the Islamic Practice of Veiling Predict Higher Levels
      of Depressive Symptoms?
AB  - Hijab or veiling is commonly practiced by Muslim women but remains controversial
      in the broader secular society. Some Western feminists argue that veiling is an
      oppressive behavior that negatively affects women by, for example, engendering
      depression. This article tests this hypothesis with a national sample of American
      Muslim women (N = 194). The results of the regression analysis did not support
      the hypothesis. Indeed, women who veiled more frequently reported lower, rather
      than higher, levels of depressive symptoms. In other words, wearing the hijab
      appears to be a protective factor in the area of depression. Given the prevalence
      of depression among women, the results have important implications for practice
      with Muslim women at both the micro and the macro levels.

PMID- 28505360
TI  - Comparative total and unbound pharmacokinetics of cefazolin administered by bolus
      versus continuous infusion in patients undergoing major surgery: a randomized
      controlled trial.
AB  - Background.: Perioperative administration of cefazolin reduces the incidence of
      perioperative infections. Intraoperative re-dosing of cefazolin is commonly given
      between 2 and 5 h after the initial dose. This study was undertaken to determine
      whether intraoperative continuous infusions of cefazolin achieve better
      probability of target attainment (PTA) and fractional target attainment (FTA)
      than intermittent dosing. Methods.: Patients undergoing major surgery received
      cefazolin 2 g before surgical incision. They were subsequently randomized to
      receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500
      mg h -1 ) of cefazolin until skin closure. Blood samples were analysed for total
      and unbound cefazolin concentrations using a validated chromatographic method.
      Population pharmacokinetic modelling was performed using Pmetrics (r) software.
      Calculations of PTA and FTA were performed for common pathogens. Results.: Ten
      patients were enrolled in each arm. A two-compartment linear model best described
      the time course of the total plasma cefazolin concentrations. The covariates that
      improved the model were body weight and creatinine clearance. Protein binding
      varied with time [mean (range) 69 (44-80)%] with a fixed 21% unbound value of
      cefazolin used for the simulations (120 min post-initial dosing). Mean ( sd )
      central volume of distribution was 5.73 (2.42) litres, and total cefazolin
      clearance was 4.72 (1.1) litres h -1 . Continuous infusions of cefazolin
      consistently achieved better drug exposures and FTA for different weight and
      creatinine clearances, particularly for less susceptible pathogens. Conclusions.:
      Our study demonstrates that intraoperative continuous infusions of cefazolin
      increase the achievement of target plasma concentrations, even with lower
      infusion doses. Renal function and body weight are important when considering the
      need for alternative dosing regimens. Clinical trial registration.: NCT02058979.

PMID- 28505359
TI  - Thoracoscopic anatomical lung segmentectomy using 3D computed tomography
      simulation without tumour markings for non-palpable and non-visualized small lung
      nodules.
AB  - OBJECTIVES: Although wedge resection can be curative for small lung tumours,
      tumour marking is sometimes required for resection of non-palpable or visually
      undetectable lung nodules as a method for identification of tumours. Tumour
      marking sometimes fails and occasionally causes serious complications. We have
      performed many thoracoscopic segmentectomies using 3D computed tomography
      simulation for undetectable small lung tumours without any tumour markings. The
      aim of this study was to investigate whether thoracoscopic segmentectomy planned
      with 3D computed tomography simulation could precisely remove non-palpable and
      visually undetectable tumours. METHODS: Between January 2012 and March 2016, 58
      patients underwent thoracoscopic segmentectomy using 3D computed tomography
      simulation for non-palpable, visually undetectable tumours. Surgical outcomes
      were evaluated. RESULTS: A total of 35, 14 and 9 patients underwent
      segmentectomy, subsegmentectomy and segmentectomy combined with adjacent
      subsegmentectomy, respectively. All tumours were correctly resected without
      tumour marking. The median tumour size and distance from the visceral pleura was
      14 +/- 5.2 mm (range 5-27 mm) and 11.6 mm (range 1-38.8 mm), respectively. Median
      values related to the procedures were operative time, 176 min (range 83-370 min);
      blood loss, 43 ml (range 0-419 ml); duration of chest tube placement, 1 day
      (range 1-8 days); and postoperative hospital stay, 5 days (range 3-12 days). Two
      cases were converted to open thoracotomy due to bleeding. Three cases required
      pleurodesis for pleural fistula. No recurrences occurred during the mean follow
      up period of 44.4 months (range 5-53 months). CONCLUSIONS: Thoracoscopic
      segmentectomy using 3D computed tomography simulation was feasible and could be
      performed to resect undetectable tumours with no tumour markings.

PMID- 28505361
TI  - The possible evolution and future of CO2-concentrating mechanisms.
AB  - CO2-concentrating mechanisms (CCMs), based either on active transport of
      inorganic carbon (biophysical CCMs) or on biochemistry involving supplementary
      carbon fixation into C4 acids (C4 and CAM), play a major role in global primary
      productivity. However, the ubiquitous CO2-fixing enzyme in autotrophs, Rubisco,
      evolved at a time when atmospheric CO2 levels were very much higher than today
      and O2 was very low and, as CO2 and O2 approached (by no means monotonically),
      today's levels, at some time subsequently many organisms evolved a CCM that
      increased the supply of CO2 and decreased Rubisco oxygenase activity. Given that
      CO2 levels and other environmental factors have altered considerably between when
      autotrophs evolved and the present day, and are predicted to continue to change
      into the future, we here examine the drivers for, and possible timing of,
      evolution of CCMs. CCMs probably evolved when CO2 fell to 2-16 times the present
      atmospheric level, depending on Rubisco kinetics. We also assess the effects of
      other key environmental factors such as temperature and nutrient levels on CCM
      activity and examine the evidence for evolutionary changes in CCM activity and
      related cellular processes as well as limitations on continuity of CCMs through
      environmental variations.

PMID- 28505364
TI  - Classification of Patients With GH Disorders May Vary According to the IGF-I
      Assay.
AB  - Context: Insulinlike growth factor I (IGF-I) measurement is essential for the
      diagnosis and management of growth hormone (GH) disorders. However, patient
      classification may vary substantially according to the assay technique.
      Objective: We compared individual patient data and classifications obtained with
      six different IGF-I assay kits in a group of patients with various GH disorders.
      Design: In this cross-sectional study, we measured IGF-I with six immunoassays in
      102 patients with active or treated acromegaly or GH deficiency. IGF-I normative
      data previously established for the same six assay kits were used to classify the
      patients (high, low, or normal IGF-I levels), using both raw data and standard
      deviation scores (SDSs). Pairwise concordance between assays was assessed with
      Bland-Altman plots and with the percentage of observed agreement and the weighted
      kappa coefficient for categorized IGF-I SDS. Results: We observed marked
      variability both across each individual's IGF-I raw data and across IGF-I SDS
      values obtained with each of the six immunoassays. Pairwise concordance between
      assay values, as assessed with the weighted kappa coefficient, ranged from 0.50
      (moderate) to 0.81 (excellent). Conclusion: Even when using normative data
      obtained in the same large population of healthy subjects and when using
      calculated IGF-I SDSs, agreement among IGF-I assay methods is only moderate to
      good. Differences in assay performance must be taken into account when evaluating
      and monitoring patients with GH disorders. This argues for the use of the same
      IGF-I assay for a given patient throughout follow-up.

PMID- 28505363
TI  - Impact of high iron intake on cognition and neurodegeneration in humans and in
      animal models: a systematic review.
AB  - Context: Accumulation of brain iron is linked to aging and protein-misfolding
      neurodegenerative diseases. High iron intake may influence important brain health
      outcomes in later life. Objective: The aim of this systematic review was to
      examine evidence from animal and human studies of the effects of high iron intake
      or peripheral iron status on adult cognition, brain aging, and neurodegeneration.
      Data Sources: MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of
      Clinical Trials, and OpenGrey databases were searched. Study Selection: Studies
      investigating the effect of elevated iron intake at all postnatal life stages in
      mammalian models and humans on measures of adult brain health were included. Data
      Extraction: Data were extracted and evaluated by two authors independently, with
      discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or
      behavioral/cognitive, biochemical, and brain morphologic findings were used to
      study the effects of iron intake or peripheral iron status on brain health. Risk
      of bias was assessed for animal and human studies. PRISMA guidelines for
      reporting systematic reviews were followed. Results: Thirty-four preclinical and
      14 clinical studies were identified from database searches. Thirty-three
      preclinical studies provided evidence supporting an adverse effect of
      nutritionally relevant high iron intake in neonates on brain-health-related
      outcomes in adults. Human studies varied considerably in design, quality, and
      findings; none investigated the effects of high iron intake in neonates/infants.
      Conclusions: Human studies are needed to verify whether dietary iron intake
      levels used in neonates/infants to prevent iron deficiency have effects on brain
      aging and neurodegenerative disease outcomes.

PMID- 28505366
TI  - Bacterioplankton assemblages in coastal ponds reflect the influence of hydrology
      and geomorphological setting.
AB  - The factors that shape microbial community assembly in aquatic ecosystems have
      been widely studied; yet it is still unclear how distinct communities within a
      connected landscape influence one another. Coastal lakes are recipients of, and
      thus are connected to, both marine and terrestrial environments. Thus, they may
      host microbial assemblages that reflect the relative degree of influence by, and
      connectivity to, either system. In order to address this idea, we interrogated
      microbial community diversity at 49 sites in seven ponds in two seasons in the
      Lake MacLeod basin, a system fed by seawater flowing inland through underground
      karst. Environmental and spatial variation within ponds explain <9% of the
      community structure, while identity of the pond that samples were taken from
      explains 50% of community variation. That is, ponds each host distinct
      assemblages despite similarities in size, environment and position in the
      landscape, indicating a dominant role for local species sorting. The ponds
      contain a substantial amount of previously unknown microbial taxa, reflecting the
      unusual nature of this inland system. Rare marine taxa, possibly dispersed from
      seawater assemblages via the underground karst connection, are abundant within
      the inland system, suggesting an important role for regional dispersal within the
      metacommunities.

PMID- 28505362
TI  - Lipidomic profiling reveals distinct differences in plasma lipid composition in
      healthy, prediabetic, and type 2 diabetic individuals.
AB  - The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been
      extensively reported, but the global lipid profiles, especially in the East Asia
      population, associated with the development of T2D remain to be characterized.
      Liquid chromatography coupled to tandem mass spectrometry was applied to detect
      the global lipidome in the fasting plasma of 293 Chinese individuals, including
      114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose
      tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual
      change in plasma lipid features with T2D patients exhibiting characteristics
      close to those of prediabetic individuals, whereas they differed significantly
      from individuals with NGT. We constructed and validated a random forest
      classifier with 28 lipidomic features that effectively discriminated T2D from NGT
      or prediabetes. Most of the selected features significantly correlated with
      diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with
      fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and
      insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as
      lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and
      lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The
      altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that
      lipid features may play a role in the pathogenesis of T2D and that such features
      may provide a basis for evaluating risk and monitoring disease development.

PMID- 28505365
TI  - Allograft Inflammatory Factor-1 Links T-Cell Activation, Interferon Response, and
      Macrophage Activation in Chronic Kawasaki Disease Arteritis.
AB  - Background: Kawasaki disease (KD) is widely viewed as an acute arteritis.
      However, our pathologic studies show that chronic coronary arteritis can persist
      long after disease onset and is closely linked with arterial stenosis.
      Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T
      lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes.
      We determined whether these immune responses persist in chronic KD arteritis, and
      we investigated the role of AIF1 in these responses. Methods: Gene expression in
      chronic KD and childhood control arteries was determined by real-time reverse
      transcriptase polymerase chain reaction, and arterial protein expression was
      determined by immunohistochemistry and immunofluorescence. Allograft inflammatory
      factor-1 small-interfering ribonucleic acid macrophage treatment was performed to
      investigate the role of AIF1 in macrophage and T lymphocyte activation. Results:
      Allograft inflammatory factor-1 protein was highly expressed in stenotic KD
      arteries and colocalized with the macrophage marker CD68. T lymphocyte and
      interferon pathway genes were significantly upregulated in chronic KD coronary
      artery tissues. Alpha interferon-induced macrophage expression of CD80 and major
      histocompatibility complex class II was dependent on AIF1, and macrophage
      expression of AIF1 was required for antigen-specific T lymphocyte activation.
      Conclusions: Allograft inflammatory factor-1, originally identified in
      posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial
      tissues. T lymphocyte and type I interferon responses persist in chronic KD
      arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I
      interferon response, macrophage activation, and antigen-specific T lymphocyte
      activation. These results suggest the likely importance of lymphocyte-myeloid
      cell cross-talk in the pathogenesis of KD arteritis and can inform selection of
      new immunotherapies for clinical trials in high-risk KD children.

PMID- 28505367
TI  - Effect of health information exchange on recognition of medication discrepancies
      is interrupted when data charges are introduced: results of a cluster-randomized
      controlled trial.
AB  - Objectives: To determine the effect of health information exchange (HIE) on
      medication prescribing for hospital inpatients in a cluster-randomized controlled
      trial, and to examine the prescribing effect of availability of information from
      a large pharmacy insurance plan in a natural experiment. Methods: Patients
      admitted to an urban hospital received structured medication reconciliation by an
      intervention pharmacist with (intervention) or without (control) access to a
      regional HIE. The HIE contained prescribing information from the largest
      hospitals and pharmacy insurance plan in the region for the first 10 months of
      the study, but only from the hospitals for the last 21 months, when data charges
      were imposed by the insurance plan. The primary endpoint was discrepancies
      between preadmission and inpatient medication regimens, and secondary endpoints
      included adverse drug events (ADEs) and proportions of rectified discrepancies.
      Results: Overall, 186 and 195 patients were assigned to intervention and control,
      respectively. Patients were 60 years old on average and took a mean of 7
      medications before admission. There was no difference between intervention and
      control in number of risk-weighted discrepancies (6.4 vs 5.8, P = .452),
      discrepancy-associated ADEs (0.102 vs 0.092 per admission, P = .964), or
      rectification of discrepancies (0.026 vs 0.036 per opportunity, P = .539).
      However, patients who received medication reconciliation with pharmacy insurance
      data available had more risk-weighted medication discrepancies identified than
      those who received usual care (8.0 vs 5.9, P = .038). Discussion and Conclusion:
      HIE may improve outcomes of medication reconciliation. Charging for access to
      medication information interrupts this effect. Efforts are needed to understand
      and increase prescribers' rectification of medication discrepancies.

PMID- 28505368
TI  - Editor's Highlight: Farnesoid X Receptor Protects Against Low-Dose Carbon
      Tetrachloride-Induced Liver Injury Through the Taurocholate-JNK Pathway.
AB  - Hepatotoxicity is of major concern for humans exposed to industrial chemicals and
      drugs. Disruption of farnesoid X receptor (FXR), a master regulator of bile acid
      (BA) metabolism, enhanced the sensitivity to liver injury in mice after toxicant
      exposure, but the precise mechanism remains unclear. In this study, the
      interconnection between BA metabolism, FXR, and chemically induced hepatotoxicity
      was investigated using metabolomics, Fxr-null mice (Fxr-/-) and hepatocytes, and
      recombinant adenoviruses. A single low-dose intraperitoneal injection of carbon
      tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more
      severe hepatocyte damage and higher induction of pro-inflammatory mediators, such
      as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-/-. Serum metabolomics analysis
      revealed marked increases in circulating taurocholate (TCA) and tauro-beta
      muricholate (T-beta-MCA) in these mice, and forced expression of bile salt export
      protein (BSEP) by recombinant adenovirus in Fxr-/- ameliorated CCl4-induced liver
      damage. Treatment of Fxr-null hepatocytes with TCA, but not T-beta-MCA,
      significantly increased c-Jun-N-terminal kinase (JNK) activation and Ccl2 mRNA
      levels, and up-regulation of Ccl2 mRNA was attenuated by co-treatment with a JNK
      inhibitor SP600125, indicating that TCA directly amplifies hepatocyte
      inflammatory signaling mainly mediated by JNK under FXR-deficiency. Additionally,
      pretreatment with SP600125 or restoration of FXR expression in liver by use of
      recombinant adenovirus, attenuated CCl4-induced liver injury. Collectively, these
      results suggest that the TCA-JNK axis is likely associated with increased
      susceptibility to CCl4-induced acute liver injury in Fxr-/-, and provide clues to
      the mechanism by which FXR and its downstream gene targets, such as BSEP,
      protects against chemically induced hepatotoxicity.

PMID- 28505370
TI  - The complete nucleotide sequence of an IncP-2 megaplasmid unveils a mosaic
      architecture comprising a putative novel blaVIM-2-harbouring transposon in
      Pseudomonas aeruginosa.
AB  - Objectives: In Pseudomonas aeruginosa , bla VIM-2 has been mostly associated with
      a chromosomal location and rarely with a plasmid backbone. Until now, only three
      complete bla VIM-2 -carrying plasmid sequences have been described in this
      species. Here we explore the modular structure of pJB37, the first bla VIM-2 
      carrying megaplasmid described in P. aeruginosa . Methods: The complete
      nucleotide sequence of plasmid pJB37 was determined with an Illumina HiSeq, with
      de novo assembly by SPAdes, annotation by RAST and searching for antimicrobial
      resistance genes and virulence factors. Conjugation assays were conducted.
      Results: Megaplasmid pJB37 (464 804 bp long and GC content of 57.2%) comprised:
      an IncP-2 repA-oriV-parAB region; a conjugative transfer region ( traF , traG ,
      virD2 and trbBCDEJLFGI genes); Tn 6356 , a new putative bla VIM-2 -carrying
      transposon; heavy metal (mercury and tellurite) resistance operons; and an
      arsenal of virulence genes. Plasmid pJB37 was transferable by conjugation to a
      spontaneous rifampicin-resistant mutant of P. aeruginosa PAO1. Here, a bla VIM-2 
      harbouring In58 integron was associated with a new complex transposable
      structure, herein named Tn 6356 , suggesting that In58 was most likely acquired
      by insertion of this element. Conclusions: The mosaic arrangement exhibited by
      the pJB37 IncP-2 megaplasmid, which highlights the vast assembly potential of
      distinct genetic elements in a Pseudomonas widespread plasmid platform, gives new
      insights into bacterial adaptation and evolution.

PMID- 28505369
TI  - Identification of an Early Male-Killing Agent in the Oriental Tea Tortrix, Homona
      magnanima.
AB  - Arthropods are frequently infected with inherited symbionts, which sometimes
      confer fitness benefits on female hosts or manipulate host reproduction. Early
      male killing, in which infected males die during embryogenesis, is induced by
      some bacteria, such as Wolbachia and Spiroplasma. A female-biased sex ratio has
      been found in Homona magnanima, collected from a tea plantation in Japan. Here,
      we examined the male-killing trait in H. magnanima and identified the agent that
      induces early male killing. The sex ratio distortion (SR) strain produced only
      females and no males, and its egg hatch rate was significantly lower than that of
      the normal (N) strain. The N strain was infected with only Wolbachia, whereas the
      SR strain was infected with both Wolbachia and Spiroplasma. Antibiotic treatment
      with 0.10% tetracycline restored the 1:1 sex ratio in the SR strain. Females
      treated with 0.05% tetracycline were positive for Spiroplasma but not for
      Wolbachia and showed a female-biased sex ratio, whereas Wolbachia-positive
      females did not revert to male killing. When inoculated with a homogenate of the
      SR strain female, females infected with only Spiroplasma produced female-biased
      offspring. Sequence analysis of the 16S rRNA gene revealed that Spiroplasma sp.
      of H. magnanima belonged to the ixodetis clade. These results indicate that
      Spiroplasma was responsible for male killing in H. magnanima. Late male killing
      is induced in H. magnanima by an RNA-like virus, and therefore this is the first
      case in which different male-killing agents expressed at different times in the
      life cycle have been found within one host species.

PMID- 28505371
TI  - The ARM Domain of ARMADILLO-REPEAT KINESIN 1 is Not Required for Microtubule
      Catastrophe But Can Negatively Regulate NIMA-RELATED KINASE 6 in Arabidopsis
      thaliana.
AB  - Microtubules are dynamic filaments, the assembly and disassembly of which are
      under precise control of various associated proteins, including motor proteins
      and regulatory enzymes. In Arabidopsis thaliana, two such proteins are the
      ARMADILLO-REPEAT KINESIN 1 (ARK1), which promotes microtubule disassembly, and
      the NIMA-RELATED KINASE 6 (NEK6), which has a role in organizing microtubule
      arrays. Previous yeast two-hybrid and in vitro pull-down assays determined that
      NEK6 can interact with ARK1 through the latter protein's Armadillo-repeat (ARM)
      cargo domain. To explore the function of the ARM domain, we generated fluorescent
      reporter fusion proteins to ARK1 lacking the ARM domain (ARK1DeltaARM-GFP) and to
      the ARM domain alone (ARM-GFP). Both of these constructs strongly associated with
      the growing plus ends of microtubules, but only ARK1DeltaARM-GFP was capable of
      inducing microtubule catastrophe and rescuing the ark1-1 root hair phenotype.
      These results indicate that neither the ARM domain nor NEK6's putative
      interaction with it is required for ARK1 to induce microtubule catastrophe. In
      further exploration of the ARK1-NEK6 relationship, we demonstrated that, despite
      evidence that NEK6 can phosphorylate ARK1 in vitro, the in vivo distribution and
      function of ARK1 were not affected by the loss of NEK6, and vice versa. Moreover,
      NEK6 and ARK1 were found to have overlapping but non-identical distribution on
      microtubules, and hormone treatments known to affect NEK6 activity did not
      stimulate interaction. These findings suggest that ARK1 and NEK6 function
      independently in microtubule dynamics and cell morphogenesis. Despite the results
      of this functional analysis, we found that overexpression of the ARM domain led
      to complete loss of NEK6 transcription, suggesting that the ARM domain might have
      a regulatory role in NEK6 expression.

PMID- 28505372
TI  - Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase
      center into an inactive state.
AB  - The emergence of multi-drug resistant bacteria is limiting the effectiveness of
      commonly used antibiotics, which spurs a renewed interest in revisiting older and
      poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors
      that target the peptidyl transferase center (PTC) on the large subunit of the
      ribosome. In this work, we have revealed the mode of action of the PTC inhibitor
      madumycin II, an alanine-containing streptogramin A antibiotic, in the context of
      a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the
      ribosome prior to the first cycle of peptide bond formation. It allows binding of
      the tRNAs to the ribosomal A and P sites, but prevents correct positioning of
      their CCA-ends into the PTC thus making peptide bond formation impossible. We
      also revealed a previously unseen drug-induced rearrangement of nucleotides U2506
      and U2585 of the 23S rRNA resulting in the formation of the U2506*G2583 wobble
      pair that was attributed to a catalytically inactive state of the PTC. The
      structural and biochemical data reported here expand our knowledge on the
      fundamental mechanisms by which peptidyl transferase inhibitors modulate the
      catalytic activity of the ribosome.

PMID- 28505374
TI  - Comment on: Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of
      healthcare/ventilator-associated MRSA pneumonia: a case-control study.

PMID- 28505373
TI  - Gene Duplication Leads to Altered Membrane Topology of a Cytochrome P450 Enzyme
      in Seed Plants.
AB  - Evolution of the phenolic metabolism was critical for the transition of plants
      from water to land. A cytochrome P450, CYP73, with cinnamate 4-hydroxylase (C4H)
      activity, catalyzes the first plant-specific and rate-limiting step in this
      pathway. The CYP73 gene is absent from green algae, and first detected in
      bryophytes. A CYP73 duplication occurred in the ancestor of seed plants and was
      retained in Taxaceae and most angiosperms. In spite of a clear divergence in
      primary sequence, both paralogs can fulfill comparable cinnamate hydroxylase
      roles both in vitro and in vivo. One of them seems dedicated to the biosynthesis
      of lignin precursors. Its N-terminus forms a single membrane spanning helix and
      its properties and length are highly constrained. The second is characterized by
      an elongated and variable N-terminus, reminiscent of ancestral CYP73s. Using as
      proxies the Brachypodium distachyon proteins, we show that the elongation of the
      N-terminus does not result in an altered subcellular localization, but in a
      distinct membrane topology. Insertion in the membrane of endoplasmic reticulum
      via a double-spanning open hairpin structure allows reorientation to the lumen of
      the catalytic domain of the protein. In agreement with participation to a
      different functional unit and supramolecular organization, the protein displays
      modified heme proximal surface. These data suggest the evolution of divergent C4H
      enzymes feeding different branches of the phenolic network in seed plants. It
      shows that specialization required for retention of gene duplicates may result
      from altered protein topology rather than change in enzyme activity.

PMID- 28505377
TI  - Performance of glomerular filtration rate estimating equations in a community
      based sample of Blacks and Whites: the multiethnic study of atherosclerosis.
AB  - Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equations are recommended for glomerular filtration rate (GFR) estimation in the
      general population. They have not been evaluated in community-based populations,
      including Blacks at higher levels of GFR, but are commonly applied in such
      populations. Methods: In an ancillary study of Multi-Ethnic Study of
      Atherosclerosis conducted at one site, we evaluated the performance of the CKD
      EPI equations for creatinine (eGFRcr), cystatin C (eGFRcys) or the combination
      (eGFRcr-cys) compared with GFR measured as plasma clearance of iohexol. Results:
      Among 294 participants, the mean age was 71 (SD 9) years, 47% were Black, 48%
      were women and the mean measured GFR (mGFR) was 72.6 (SD 18.8) mL/min/1.73 m2.
      The CKD-EPI equations overestimated mGFR with a larger median bias for eGFRcr and
      eGFRcr-cys than eGFRcys [-8.3 (95% confidence interval -9.7, -6.5), -7.8 (-9.2, 
      6.2) and -3.7 (-5.0, -1.8) mL/min/1.73 m2, respectively], with smaller bias for
      those with lower compared with higher eGFR and by race compared with sex.
      Conclusion: The small differential bias of the CKD-EPI equation between races
      suggests that they can be used in Blacks as well as Whites in older community
      based adults. The large differential bias in women versus men in all equations is
      in contrast to other studies and is unexplained. Further studies are required in
      multiracial and multiethnic community-based cohorts, taking into account
      differences in GFR measurement methods.

PMID- 28505378
TI  - Overweight and abdominal obesity in women of childbearing age of Russian, Somali
      and Kurdish origin and the general Finnish population.
AB  - Background: Migrant background and higher parity may increase the risk of being
      overweight. We compared the prevalence of overweight (body mass index >=25 kg/m2)
      and abdominal obesity (waist-to-height ratio >=0.5) between non-pregnant migrant
      and Finnish women aged 18-45 years. Methods: The participants were 165 Russian,
      164 Somali and 179 Kurdish origin women from the cross-sectional Migrant Health
      and Wellbeing study. The reference group included 388 women from the general
      Finnish population. Body anthropometrics were measured. The main statistical
      methods were logistic regression adjusted for sociodemographic and reproductive
      variables. Results: The unadjusted prevalence of overweight and obesity,
      respectively, were higher among Somali (32.9%, 30.9%, P < 0.001) and Kurdish
      women (41.1%, 19.5%, P < 0.001) than among Finnish women (19.9%, 9.8%). The
      adjusted odds ratios (95% CI) for overweight (including obesity) were 0.54 (0.33;
      0.89) for Russian, 2.89 (1.66; 5.03) for Somali and 2.56 (1.64; 4.00) for Kurdish
      women compared with Finnish women. Kurdish women had 2.96-fold (1.75; 5.00)
      adjusted odds ratio for abdominal obesity compared with Finnish women. Being
      parous was associated with overweight and abdominal obesity among Kurdish women.
      Conclusions: Overweight and obesity were very common among Somali and Kurdish
      origin women. Information on diet and physical activity in these groups is
      needed.

PMID- 28505375
TI  - Between a Pod and a Hard Test: The Deep Evolution of Amoebae.
AB  - Amoebozoa is the eukaryotic supergroup sister to Obazoa, the lineage that
      contains the animals and Fungi, as well as their protistan relatives, and the
      breviate and apusomonad flagellates. Amoebozoa is extraordinarily diverse,
      encompassing important model organisms and significant pathogens. Although
      amoebozoans are integral to global nutrient cycles and present in nearly all
      environments, they remain vastly understudied. We present a robust phylogeny of
      Amoebozoa based on broad representative set of taxa in a phylogenomic framework
      (325 genes). By sampling 61 taxa using culture-based and single-cell
      transcriptomics, our analyses show two major clades of Amoebozoa, Discosea, and
      Tevosa. This phylogeny refutes previous studies in major respects. Our results
      support the hypothesis that the last common ancestor of Amoebozoa was sexual and
      flagellated, it also may have had the ability to disperse propagules from a
      sporocarp-type fruiting body. Overall, the main macroevolutionary patterns in
      Amoebozoa appear to result from the parallel losses of homologous characters of a
      multiphase life cycle that included flagella, sex, and sporocarps rather than
      independent acquisition of convergent features.

PMID- 28505376
TI  - Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in
      keratinocytes and its potential implications on species-specific gene expression
      and phenotypes.
AB  - Although epidermal keratinocyte development and differentiation proceeds in
      similar fashion between humans and mice, evolutionary pressures have also wrought
      significant species-specific physiological differences. These differences between
      species could arise in part, by the rewiring of regulatory network due to changes
      in the global targets of lineage-specific transcriptional master regulators such
      as p63. Here we have performed a systematic and comparative analysis of the p63
      target gene network within the integrated framework of the transcriptomic and
      epigenomic landscape of mouse and human keratinocytes. We determined that there
      exists a core set of ~1600 genomic regions distributed among enhancers and super
      enhancers, which are conserved and occupied by p63 in keratinocytes from both
      species. Notably, these DNA segments are typified by consensus p63 binding motifs
      under purifying selection and are associated with genes involved in key
      keratinocyte and skin-centric biological processes. However, the majority of the
      p63-bound mouse target regions consist of either murine-specific DNA elements
      that are not alignable to the human genome or exhibit no p63 binding in the
      orthologous syntenic regions, typifying an occupancy lost subset. Our results
      suggest that these evolutionarily divergent regions have undergone significant
      turnover of p63 binding sites and are associated with an underlying inactive and
      inaccessible chromatin state, indicative of their selective functional activity
      in the transcriptional regulatory network in mouse but not human. Furthermore, we
      demonstrate that this selective targeting of genes by p63 correlates with subtle,
      but measurable transcriptional differences in mouse and human keratinocytes that
      converges on major metabolic processes, which often exhibit species-specific
      trends. Collectively our study offers possible molecular explanation for the
      observable phenotypic differences between the mouse and human skin and broadly
      informs on the prevailing principles that govern the tug-of-war between
      evolutionary forces of rigidity and plasticity over transcriptional regulatory
      programs.

PMID- 28505379
TI  - Analysis of CFB, a cytokinin-responsive gene of Arabidopsis thaliana encoding a
      novel F-box protein regulating sterol biosynthesis.
AB  - Protein degradation by the ubiquitin-26S proteasome pathway is important for the
      regulation of cellular processes, but the function of most F-box proteins
      relevant to substrate recognition is unknown. We describe the analysis of the
      gene Cytokinin-induced F-box encoding (CFB, AT3G44326), identified in a meta
      analysis of cytokinin-related transcriptome studies as one of the most robust
      cytokinin response genes. F-box domain-dependent interaction with the E3
      ubiquitin ligase complex component ASK1 classifies CFB as a functional F-box
      protein. Apart from F-box and transmembrane domains, CFB contains no known
      functional domains. CFB is expressed in all plant tissues, predominantly in root
      tissue. A ProCFB:GFP-GUS fusion gene showed strongest expression in the lateral
      root cap and during lateral root formation. CFB-GFP fusion proteins were mainly
      localized in the nucleus and the cytosol but also at the plasma membrane. cfb
      mutants had no discernible phenotype, but CFB overexpressing plants showed
      several defects, such as a white upper inflorescence stem, similar to the
      hypomorphic cycloartenol synthase mutant cas1-1. Both CFB overexpressing plants
      and cas1-1 mutants accumulated the CAS1 substrate 2,3-oxidosqualene in the white
      stem tissue, the latter even more after cytokinin treatment, indicating
      impairment of CAS1 function. This suggests that CFB may link cytokinin and the
      sterol biosynthesis pathway.

PMID- 28505382
TI  - Facile Phenylphosphinidene Transfer Reactions from Carbene-Phosphinidene Zinc
      Complexes.
AB  - Phosphinidenes [R-P] are convenient P1 building blocks for the synthesis of a
      plethora of organophosphorus compounds. Thus far, transition-metal-complexed
      phosphinidenes have been used for their singlet ground-state reactivity to
      promote selective addition and insertion reactions. One disadvantage of this
      approach is that after transfer of the P1 moiety to the substrate, a challenging
      demetallation step is required to provide the free phosphine. We report a simple
      method that enables the Lewis acid promoted transfer of phenylphosphinidene,
      [PhP], from NHC=PPh adducts (NHC=N-heterocyclic carbene) to various substrates to
      produce directly uncoordinated phosphorus heterocycles that are difficult to
      obtain otherwise.

PMID- 28505380
TI  - Potential reward reduces the adverse impact of negative distractor stimuli.
AB  - Knowledge about interactions between reward and negative processing is
      rudimentary. Here, we employed functional MRI to probe how potential reward
      signaled by advance cues alters aversive distractor processing during perception.
      Behaviorally, the influence of aversive stimuli on task performance was reduced
      during the reward compared to no-reward condition. In the brain, at the task
      phase, paralleling the observed behavioral pattern, we observed significant
      interactions in the anterior insula and dorsal anterior cingulate cortex, such
      that responses during the negative (vs neutral) condition were reduced during the
      reward compared to no-reward condition. Notably, negative distractor processing
      in the amygdala appeared to be independent of the reward manipulation. During the
      initial cue phase, we observed increased reward-related responses in the ventral
      striatum/accumbens, which were correlated with behavioral interference scores at
      the subsequent task phase, revealing that participants with increased reward
      related responses exhibited a greater behavioral benefit of reward in reducing
      the adverse effect of negative images. Furthermore, during processing of reward
      (vs no-reward) cues, the ventral striatum exhibited stronger functional
      connectivity with fronto-parietal regions important for attentional control.
      Together, our findings contribute to the understanding of how potential reward
      influences attentional control and reduces negative distractor processing in the
      human brain.

PMID- 28505383
TI  - Arboreal camera trapping expands Hyla versicolor complex (Hylidae) canopy use to
      new heights.

PMID- 28505381
TI  - Insulin Resistance Disrupts the Interaction Between AKT and the NMDA Receptor and
      the Inactivation of the CaMKIV/CREB Pathway in Minimal Hepatic Encephalopathy.
AB  - Hepatic cirrhosis-induced Minimal hepatic encephalopathy (MHE) has been
      characterized for cognitive dysfunction and central nervous system (CNS) insulin
      resistance (IR) has been acknowledged to be closely correlated with cognitive
      impairment while hepatic cirrhosis has been recognized to induce IR. Thus, this
      study aimed to investigate whether CNS IR occurred in MHE and induced MHE, as
      well as the underlying mechanism. We found IR in the MHE rats, an especially
      decreased level of the insulin receptor (InsR), and an increased serine
      phosphorylation of IRS1 in CNS. PI3K/AKT pathway signaling to the phosphorylation
      of N-Methyl-d-Aspartate receptors (NMDA receptors, NRs, NR1/NR2B) and downstream
      activation of the CaMKIV/CREB pathway and final production of neurotrophic
      factors were triggered by insulin, but impaired in the MHE rats. Additionally,
      CNS IR, memory impairment, the desensitization of the PI3K/AKT/NMDA receptor
      (NR)/CaMKIV/CREB pathway and decreased production of BDNF/NT3 in MHE rats were
      improved by rosiglitazone (RSG). These results suggested that IR, which induces
      the deficits in the insulin-mediated PI3K/AKT/NR/CaMKIV/CREB/neurotrophin pathway
      and subsequent memory decline, contributes to the pathogenesis of MHE.

PMID- 28505384
TI  - A Systematic Review of the Effect of Therapists' Internalized Models of
      Relationships on the Quality of the Therapeutic Relationship.
AB  - OBJECTIVE: Previous reviews have found equivocal evidence of an association
      between therapists' internalized relational models and the therapeutic
      relationship and have neglected empirical literature based on Sullivan's notion
      of introject. This review expanded upon previous reviews to examine the effect of
      therapist internalized relational models on a broader conceptualization of the
      therapeutic relationship. METHOD: Systematic search processes identified 22
      papers measuring therapist attachment and/or introject and therapeutic
      relationship: 19 on therapist attachment, 5 on introject with 2 overlapping.
      RESULTS: Overall, despite heterogeneity in design and variable methodological
      quality, evidence suggests that therapist attachment affects therapeutic
      relationship quality, observed in client-rated evaluation, therapist negative
      countertransference, empathy, and problems in therapy. Interaction effects
      between client and therapist attachment style were also found. Evidence
      suggesting that therapist introject also affects therapeutic relationship
      quality, including therapists' manner and feelings toward their clients, was
      stronger. CONCLUSION: Evidence clearly shows that therapists' internalized
      relational models affect the therapeutic relationship. More research is necessary
      to clarify exactly how therapist and client internalized relational models
      interact and translate these findings into clinical practice.

PMID- 28505385
TI  - Professional Burnout, Early Maladaptive Schemas, and Physical Health in Clinical
      and Counselling Psychology Trainees.
AB  - OBJECTIVE: Little is known about the personal factors that increase vulnerability
      to job-related stress and burnout among psychologists in training. This study was
      based on a large international sample and aimed to explore the role of early
      maladaptive schemas (EMS) in predicting vulnerability to burnout, as well as
      attendant effects on short-term physical health, in clinical and counseling
      postgraduate psychology trainees. METHOD: An online, quantitative, cross
      sectional survey method design was used to collect self-report data that measured
      burnout, EMS, and physical health from 1,297 trainees. RESULTS: Only the
      unrelenting standards (US) schema predicted high burnout among trainees. The most
      commonly endorsed physical health symptoms were back and neck pain and tiredness,
      and were more severe for those experiencing high burnout. CONCLUSION: The current
      study contributes to our understanding of the role of the US EMS in the evolution
      of burnout in trainees and has implications for the development of self-awareness
      training programs for this population.

PMID- 28505387
TI  - Interspecific combat observed among viperid snakes.

PMID- 28505388
TI  - Tuning Up or Down the Critical Thickness in LaAlO3 /SrTiO3 through In Situ
      Deposition of Metal Overlayers.
AB  - The quasi 2D electron system (q2DES) that forms at the interface between LaAlO3
      and SrTiO3 has attracted much attention from the oxide electronics community. One
      of its hallmark features is the existence of a critical LaAlO3 thickness of 4
      unit-cells (uc) for interfacial conductivity to emerge. In this paper, the
      chemical, electronic, and transport properties of LaAlO3 /SrTiO3 samples capped
      with different metals grown in a system combining pulsed laser deposition,
      sputtering, and in situ X-ray photoemission spectroscopy are investigated. The
      results show that for metals with low work function a q2DES forms at 1-2 uc of
      LaAlO3 and is accompanied by a partial oxidation of the metal, a phenomenon that
      affects the q2DES properties and triggers the formation of defects. In contrast,
      for noble metals, the critical thickness is increased above 4 uc. The results are
      discussed in terms of a hybrid mechanism that incorporates electrostatic and
      chemical effects.

PMID- 28505386
TI  - C/D-box snoRNAs form methylating and non-methylating ribonucleoprotein complexes:
      Old dogs show new tricks.
AB  - C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non-coding
      RNAs that have been long known to perform 2'-O-methylation of rRNAs. However,
      approximately half of human SNORDs have no predictable rRNA targets, and numerous
      SNORDs have been associated with diseases that show no defects in rRNAs, among
      them Prader-Willi syndrome, Duplication 15q syndrome and cancer. This apparent
      discrepancy has been addressed by recent studies showing that SNORDs can act to
      regulate pre-mRNA alternative splicing, mRNA abundance, activate enzymes, and be
      processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent
      biochemical studies have shown that a given SNORD can form both methylating and
      non-methylating ribonucleoprotein complexes, providing an indication of the
      likely physical basis for such diverse new functions. Thus, SNORDs are more
      structurally and functionally diverse than previously thought, and their role in
      gene expression is under-appreciated. The action of SNORDs in non-methylating
      complexes can be substituted with oligonucleotides, allowing devising therapies
      for diseases like Prader-Willi syndrome.

PMID- 28505389
TI  - Nitrogen and phosphorus availabilities interact to modulate leaf trait scaling
      relationships across six plant functional types in a controlled-environment
      study.
AB  - Nitrogen (N) and phosphorus (P) have key roles in leaf metabolism, resulting in a
      strong coupling of chemical composition traits to metabolic rates in field-based
      studies. However, in such studies, it is difficult to disentangle the effects of
      nutrient supply per se on trait-trait relationships. Our study assessed how high
      and low N (5 mM and 0.4 mM, respectively) and P (1 mM and 2 MUM, respectively)
      supply in 37 species from six plant functional types (PTFs) affected
      photosynthesis (A) and respiration (R) (in darkness and light) in a controlled
      environment. Low P supply increased scaling exponents (slopes) of area-based log
      log A-N or R-N relationships when N supply was not limiting, whereas there was no
      P effect under low N supply. By contrast, scaling exponents of A-P and R-P
      relationships were altered by P and N supply. Neither R : A nor light inhibition
      of leaf R was affected by nutrient supply. Light inhibition was 26% across
      nutrient treatments; herbaceous species exhibited a lower degree of light
      inhibition than woody species. Because N and P supply modulates leaf trait-trait
      relationships, the next generation of terrestrial biosphere models may need to
      consider how limitations in N and P availability affect trait-trait relationships
      when predicting carbon exchange.

PMID- 28505390
TI  - Correlation between Chiral Modifier Adsorption and Enantioselectivity in
      Hydrogenation Catalysis.
AB  - Infrared absorption spectroscopy performed in situ at the solid-liquid interface
      revealed that the adsorption on platinum supported catalysts of 1-(1-naphthyl)
      ethylamine, which is used as a chiral modifier in hydrogenation catalysis, occurs
      through the amine group, not the aromatic ring as is widely believed. Comparisons
      were performed against a set of related modifier compounds with targeted
      substitutions to help identify the key moiety involved in the adsorption. It was
      determined that neither naphthalene-based modifiers without amine groups nor
      those with tertiary amine moieties are capable of adsorbing on the metal surface
      to any significant extent. A direct correlation was also found between the
      ability of the amines to adsorb on the platinum surface and their performance as
      chiral modifiers that impart enantioselectivity to the hydrogenation of alpha
      keto esters such as ethyl pyruvate.

PMID- 28505391
TI  - Establishment of a novel quantum dots-encoded microbead-based flow cytometric
      method for quantification of soluble FcepsilonRIalpha in serum.
AB  - The soluble form of the transmembrane glycoprotein, FcepsilonRIalpha which
      corresponds to the high-affinity receptor for IgE, is found in serum. Growing
      evidence suggests the pathogenic role of IgE and FcepsilonRI in systemic lupus
      erythematosus (SLE). The goal of this study is to develop a sensitive and
      standardized cytometric assay for quantification of sFcepsilonRIalpha. A membrane
      emulsification technique was utilized to incorporate CuInS2 /ZnS quantum dots and
      Fe3 O4 nanoparticles into poly (styrene-co-maleic anhydride) microbeads. The
      beads were then carboxylated and coated with capture antibody monoclonal anti
      human FcepsilonRIalpha. This antibody binds to FcepsilonRIalpha but does not
      block the binding of FcepsilonRIalpha to IgE. After incubation with standards or
      serum samples, the microbeads were incubated with excessive native human IgE,
      followed by incubation with Phycoerythrin (PE) conjugated anti-human IgE. The
      resulting quantum dot microbeads were gated, and sFcepsilonRIalpha quantification
      was analyzed based on PE fluorescence intensity. The method exhibited good
      linearity (R2  > 0.99), and the limit of detection was established at 0.29 ng/mL
      with the dynamic range of up to 200 ng/mL. The precision of the assay validated
      by intra- and inter-assay variability met the acceptance criteria with the mean
      recovery falling within 80-110% of the theoretical concentration and a
      corresponding CV < 20%. We tested 149 serum samples which 89 were from SLE
      patients and 60 were from healthy volunteers. For the first time, we detected an
      increased sFcepsilonRIalpha level in the serum of SLE patients, which was
      confirmed by a commercial ELISA kit. Compared to ELISA, this novel method is more
      sensitive and efficient. It allows for the simple comparative analysis of
      sFcepsilonRIalpha levels in health and disease. (c) 2017 International Society
      for Advancement of Cytometry.

PMID- 28505392
TI  - Beneficial effects of ginger Zingiber officinale Roscoe on obesity and metabolic
      syndrome: a review.
AB  - In recent years, metabolic syndromes (MetSs), including diabetes mellitus,
      dyslipidemia, and cardiovascular diseases, have become a common health problem in
      both developed and developing countries. Accumulating data have suggested that
      traditional herbs might be able to provide a wide range of remedies in prevention
      and treatment of MetSs. Ginger (Zingiber officinale Roscoe, Zingiberaceae) has
      been documented to ameliorate hyperlipidemia, hyperglycemia, oxidative stress,
      and inflammation. These beneficial effects are mediated by transcription factors,
      such as peroxisome proliferator-activated receptors, adenosine monophosphate
      activated protein kinase, and nuclear factor kappaB. This review focuses on
      recent findings regarding the beneficial effects of ginger on obesity and related
      complications in MetS and discusses its potential mechanisms of action. This
      review provides guidance for further applications of ginger for personalized
      nutrition and medicine.

PMID- 28505393
TI  - The science behind One Health: at the interface of humans, animals, and the
      environment.
AB  - Humans face a grand quality-of-life challenge as growing demands for resources
      for an ever-expanding population threaten the existence of wildlife populations,
      degrade land, and pollute air and water. Public investment and policy decisions
      that will shape future interactions of humans, animals, and the environment need
      scientific input to help find common ground for durable and sustainable success.
      The Second International Conference on One Medicine One Science brought together
      a broad range of scientists, trainees, regulatory authorities, and health experts
      from 34 countries to inform and discuss the human impacts of air quality; the
      complexities of water quality, access, and conflicts; the opportunities and
      uncertainties in precision medicine; and the role of science communication in
      health policy formulation. Workshops focused on the roles and development of
      physician-scientists and multidisciplinary teams in complex problem solving, Big
      Data tools for analysis and visualization, international policy development
      processes, and health models that benefit animals and humans. Key realizations
      were that local and regional health challenges at the interface of humans,
      animals, and the environment are variations of the same overarching conflicts and
      that international gatherings provide new opportunities for investigation and
      policy development that are broadly applicable.

PMID- 28505394
TI  - 1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-beta
      lactamases.
AB  - Metallo-beta-lactamases (MBLs) cause resistance of Gram-negative bacteria to beta
      lactam antibiotics and are of serious concern, because they can inactivate the
      last-resort carbapenems and because MBL inhibitors of clinical value are still
      lacking. We previously identified the original binding mode of 4-amino-2,4
      dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the
      dizinc active site of the L1 MBL. Herein we present the crystallographic
      structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2
      dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding
      mode of IIIB was similar but reverse to that of IIIA. The 3 D structures
      suggested that the triazole-thione scaffold was suitable to bind to the catalytic
      site of dizinc metalloenzymes. On the basis of these results, we synthesized 54
      analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range
      toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1,
      and IMP-1). Five of these exhibited a significant inhibition of at least four
      enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured
      either halogen or bulky bicyclic aryl substituents. Finally, some compounds were
      also tested on several microbial dinuclear zinc-dependent hydrolases belonging to
      the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their
      activity toward structurally similar but functionally distinct enzymes. Whereas
      the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial
      glyoxalase II were in the 10 MUm range.

PMID- 28505395
TI  - Claudin peptidomimetics modulate tissue barriers for enhanced drug delivery.
AB  - The blood-brain barrier (BBB) formed by the microvascular endothelium limits
      cerebral drug delivery. The paraendothelial cleft is sealed by tight junctions
      (TJs) with a major contribution from claudin-5, which we selected as a target to
      modulate BBB permeability. For this purpose, drug-enhancer peptides were designed
      based on the first extracellular loop (ECL) of claudin-5 to allow transient BBB
      permeabilization. Peptidomimetics (C5C2 and derivatives, nanomolar affinity to
      claudin-5) size-selectively (<=40 kDa) and reversibly (12-48 h) increased the
      permeability of brain endothelial and claudin-5-transfected epithelial cell
      monolayers. Upon peptide uptake, the number of TJ strand particles diminished,
      claudin-5 was downregulated and redistributed from cell-cell contacts to the
      cytosol, and the cell shape was altered. Cellular permeability of doxorubicin
      (cytostatic drug, 580 Da) was enhanced after peptide administration. Mouse
      studies (3.5 MUmol/kg i.v.) confirmed that, for both C5C2 and a d-amino acid
      derivative, brain uptake of Gd-diethylene-triamine penta-acetic acid (547 Da) was
      enhanced within 4 h of treatment. On the basis of our functional data, circular
      dichroism measurements, molecular modeling, and docking experiments, we suggest
      an association model between beta-sheets flanked by alpha-helices, formed by
      claudin-5 ECLs, and the peptides. In conclusion, we identified claudin-5
      peptidomimetics that improve drug delivery through endothelial and epithelial
      barriers expressing claudin-5.

PMID- 28505401
TI  - The influence of a composite hospital volume on outcomes for gastric cancer
      surgery: A Dutch population-based study.
AB  - BACKGROUND: Volume-outcome associations for complex surgical procedures have
      motivated centralization of care worldwide. The aim of this study was to
      investigate the association between overall hospital experience with complex
      upper gastrointestinal (GI) cancer resections and outcomes after gastric cancer
      surgery. METHODS: Data on all patients (n = 4837) who underwent a resection for
      non metastatic invasive gastric cancer between 2005 and 2014 were obtained from
      the Netherlands Cancer Registry (NCR). Annual hospital volume categories were
      based on the combined volume of gastrectomies, esophagectomies, and
      pancreatectomies (composite hospital volume). Volume-outcome analyses were
      performed for lymph node yield, 30-day mortality, and overall survival. RESULTS:
      The proportion of gastric cancer resections performed in hospitals with an annual
      composite hospital volume of >=40 upper GI cancer resections increased from 6% in
      2005 to 80% in 2014. A higher composite hospital volume was univariably
      associated with a higher lymph node yield, lower 30-day mortality, and increased
      overall survival. Statistical significance was lost after adjusting for case mix.
      But, sub group analysis including only elderly patients (>=75 years) showed a
      significant association between composite hospital volume and 30-day mortality.
      CONCLUSION: In the Netherlands, an increasing proportion of gastric cancer
      resections is performed in hospitals with a high composite hospital volume of
      gastric, esophageal, and pancreatic cancer resections. Special attention is
      warranted to referral of elderly patients, as these patients might specifically
      benefit from this centralization.

PMID- 28505403
TI  - Prediction of the Wetting Behavior of Active and Hole-Transport Layers for
      Printed Flexible Electronic Devices Using Molecular Dynamics Simulations.
AB  - Molecular dynamics (MD) simulations were used to predict the wetting behavior of
      materials typical of active and hole-transport layers in organic electronics by
      evaluating their contact angles and adhesion energies. The active layer (AL) here
      consists of a blend of poly(3-hexylthiophene) and phenyl-C61-butyric acid methyl
      ester (P3HT:PCBM), whereas the hole-transport layer (HTL) consists of a blend of
      poly(3,4-ethylenedioxythiophene) and poly(styrenesulfonate) (PEDOT:PSS).
      Simulations of the wetting of these surfaces by multiple solvents show that
      formamide, glycerol, and water droplet contact angle trends correlate with
      experimental values. However, droplet simulations on surfaces are computationally
      expensive and would be impractical for routine use in printed electronics and
      other applications. As an alternative, contact angle measurements can be related
      to adhesion energy, which can be calculated more quickly and easily from
      simulations and has been shown to correlate with contact angles. Calculations of
      adhesion energy for 16 different solvents were used to rapidly predict the
      wetting behavior of solvents on the AL and HTL surfaces. Among the tested
      solvents, pentane and hexane exhibit low and similar adhesion energy on both of
      the surfaces considered. This result suggests that among the tested solvents,
      pentane and hexane exhibit strong potential as orthogonal solvent in printing
      electronic materials onto HTL and AL materials. The simulation results further
      show that MD can accelerate the evaluation of processing parameters for printed
      electronics.

PMID- 28505402
TI  - Influence of Asymmetric Contact Form on Contact Resistance and Schottky Barrier,
      and Corresponding Applications of Diode.
AB  - We have fabricated carbon nanotube and MoS2 field-effect transistors with
      asymmetric contact forms of source-drain electrodes, from which we found the
      current directionality of the devices and different contact resistances under the
      two current directions. By designing various structures, we can conclude that the
      asymmetric electrical performance was caused by the difference in the effective
      Schottky barrier height (PhiSB) caused by the different contact forms. A detailed
      temperature-dependent study was used to extract and compare the PhiSB for both
      contact forms of CNT and MoS2 devices; we found that the PhiSB for the metal-on
      semiconductor form was much lower than that of the semiconductor-on-metal form
      and is suitable for all p-type, n-type, or ambipolar semiconductors. This
      conclusion is meaningful with respect to the design and application of
      nanomaterial electronic devices. Additionally, using the difference in barrier
      height caused by the contact forms, we have also proposed and fabricated Schottky
      barrier diodes with a current ratio up to 104; rectifying circuits consisting of
      these diodes were able to work in a wide frequency range. This design avoided the
      use of complex chemical doping or heterojunction methods to achieve fundamental
      diodes that are relatively simple and use only a single material; these may be
      suitable for future application in nanoelectronic radio frequency or integrated
      circuits.

PMID- 28505404
TI  - Activated Porous Carbon Spheres with Customized Mesopores through Assembly of
      Diblock Copolymers for Electrochemical Capacitor.
AB  - A series of porous carbon spheres with precisely adjustable mesopores (4-16 nm),
      high specific surface area (SSA, ~2000 m2 g-1), and submicrometer particle size
      (~300 nm) was synthesized through a facile coassembly of diblock polymer micelles
      with a nontoxic dopamine source and a common postactivation process. The mesopore
      size can be controlled by the diblock polymer, polystyrene-block-poly(ethylene
      oxide) (PS-b-PEO) templates, and has an almost linear dependence on the square
      root of the degree of polymerization of the PS blocks. These advantageous
      structural properties make the product a promising electrode material for
      electrochemical capacitors. The electrochemical capacitive performance was
      studied carefully by using symmetrical cells in a typical organic electrolyte of
      1 M tetraethylammonium tetrafluoroborate/acetonitrile (TEA BF4/AN) or in an ionic
      liquid electrolyte of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4),
      displaying a high specific capacitance of 111 and 170 F g-1 at 1 A g-1,
      respectively. The impacts of pore size distribution on the capacitance
      performance were thoroughly investigated. It was revealed that large mesopores
      and a relatively low ratio of micropores are ideal for realizing high SSA
      normalized capacitance. These results provide us with a simple and reliable way
      to screen future porous carbon materials for electrochemical capacitors and
      encourage researchers to design porous carbon with high specific surface area,
      large mesopores, and a moderate proportion of micropores.

PMID- 28505405
TI  - Structural Basis for Xenosiderophore Utilization by the Human Pathogen
      Staphylococcus aureus.
AB  - Staphylococcus aureus produces a cocktail of metallophores (staphylopine,
      staphyloferrin A, and staphyloferrin B) to scavenge transition metals during
      infection of a host. In addition, S. aureus displays the extracellular surface
      lipoproteins FhuD1 and FhuD2 along with the ABC transporter complex FhuCBG to
      facilitate the use of hydroxamate xenosiderophores such as desferrioxamine B
      (DFOB) for iron acquisition. DFOB is used as a chelation therapy to treat human
      iron overload diseases and has been linked to an increased risk of S. aureus
      infections. We used a panel of synthetic DFOB analogs and a FhuD2-selective
      trihydroxamate sideromycin to probe xenosiderophore utilization in S. aureus and
      establish structure-activity relationships for Fe(III) binding, FhuD2 binding, S.
      aureus growth promotion, and competition for S. aureus cell entry. Fe(III)
      binding assays and FhuD2 intrinsic fluorescence quenching experiments revealed
      that diverse chemical modifications of the terminal ends of linear ferrioxamine
      siderophores influences Fe(III) affinity but not FhuD2 binding. Siderophore
      sideromycin competition assays and xenosiderophore growth promotion assays
      revealed that S. aureus SG511 and ATCC 11632 can distinguish between competing
      siderophores based exclusively on net charge of the siderophore-Fe(III) complex.
      Our work provides a roadmap for tuning hydroxamate xenosiderophore scaffolds to
      suppress (net negative charge) or enhance (net positive or neutral charge) uptake
      by S. aureus for applications in metal chelation therapy and siderophore-mediated
      antibiotic delivery, respectively.

PMID- 28505406
TI  - Electrolyte Volume Effects on Electrochemical Performance and Solid Electrolyte
      Interphase in Si-Graphite/NMC Lithium-Ion Pouch Cells.
AB  - This study aims to explore the correlations between electrolyte volume,
      electrochemical performance, and properties of the solid electrolyte interphase
      in pouch cells with Si-graphite composite anodes. The electrolyte is 1.2 M LiPF6
      in ethylene carbonate:ethylmethyl carbonate with 10 wt % fluoroethylene
      carbonate. Single layer pouch cells (100 mA h) were constructed with 15 wt % Si
      graphite/LiNi0.5Mn0.3CO0.2O2 electrodes. It is found that a minimum electrolyte
      volume factor of 3.1 times to the total pore volume of cell components (cathode,
      anode, and separator) is needed for better cycling stability. Less electrolyte
      causes increases in ohmic and charge transfer resistances. Lithium dendrites are
      observed when the electrolyte volume factor is low. The resistances from the
      anodes become significant as the cells are discharged. Solid electrolyte
      interphase thickness grows as the electrolyte volume factor increases and is
      nonuniform after cycling.

PMID- 28505408
TI  - Ion Mobility, Hydrogen/Deuterium Exchange, and Isotope Scrambling: Tools to Aid
      Compound Identification in 'Omics Mixtures.
AB  - Liquid chromatography tandem mass spectrometry (LC-MS/MS), a widely used method
      for comparative 'omics analysis, experiences challenges with compound
      identification due to matrix effects, difficulty in separating isomer and
      isobaric ions, and long analysis times. Ion mobility spectrometry (IMS) has
      proven to be useful in separating isomer and isobar ions; however, IMS-MS suffers
      from decreased peak capacity due to the correlation in ion size and mass. In
      proof-of-principle experiments, the use of gas-phase hydrogen/deuterium exchange
      (HDX) combined with IMS-MS/MS techniques is demonstrated to offer advantages for
      compound identification. Measurements providing unique information for ions
      include m/z value, drift time in He buffer gas, drift time in He and D2O buffer
      gases, deuterium incorporation pattern (isotopic distribution), deuterium
      incorporation pattern after collisional activation, and fragment ion deuterium
      incorporation pattern upon collision-induced dissociation (CID). These techniques
      are here shown to be highly reproducible (drift time coefficients of variation <
      1.0% and isotopic pattern root-mean-square deviations of 0.5-1.5%) while
      demonstrating an increased ability to distinguish individual molecules from
      diverse classes of compounds (peptides, catecholamines, nucleosides, amino acids,
      etc.). The concept of using such (and similar) information for rapid, high
      throughput molecular identification via database searching of standard libraries
      is briefly discussed, and an example of such usage is presented for a bonafide
      metabolite extract sample.

PMID- 28505407
TI  - N-Phenylacetylation and Nonribosomal Peptide Synthetases with Substrate
      Promiscuity for Biosynthesis of Heptapeptide Variants, JBIR-78 and JBIR-95.
AB  - JBIR-78 (1) and JBIR-95 (2), both of which are heptapeptide derivatives isolated
      from Kibdelosporangium sp. AK-AA56, have the same amino acid sequences except for
      the second amino acid: phenylacetic acid (Paa)-l-Val-d-Asp (1)/d-cysteic acid (2)
      l-Ala-(3S)-3-hydroxy-d-Leu-Gly-d-Ala-l-Phe. Heterologous expression of the
      biosynthetic gene cluster including genes encoding nonribosomal peptide
      synthetases (NRPS) and in vitro assays with recombinant Orf3, an l-cysteic acid
      synthase homologue, suggested the single A domain in module 2 activates both l
      Asp and l-cysteic acid to yield 1 and 2, respectively, although the substrate
      specificities of the A domains of NRPSs are usually strict. Biosynthetic
      mechanism of introduction of N-terminal Paa was also investigated. Recombinant
      Orf1 and Orf2 similar to subunits of pyruvate dehydrogenase complex catalyzed the
      conversion of phenylpyruvate into phenylacetyl-CoA together with dihydrolipoyl
      dehydrogenase whose encoding gene is located outside of the gene cluster.
      Moreover, we showed that phenylacetyl-CoA was directly condensed with l-Val,
      which was tethered to a peptidyl carrier protein, at the first condensation
      domain in the NRPS.

PMID- 28505409
TI  - Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated
      Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than
      Healthy Cells.
AB  - Although acute pulmonary toxicity of carbon nanotubes (CNTs) has been extensively
      investigated, the knowledge of potential health effects following chronic
      occupational exposure is currently limited and based only upon in vivo
      approaches. Our aim was to realistically mimic subchronic inhalation of
      multiwalled CNTs (MWCNTs) in vitro, using the air-liquid interface cell exposure
      (ALICE) system for aerosol exposures on reconstituted human bronchial tissue from
      healthy and asthmatic donors. The reliability and sensitivity of the system were
      validated using crystalline quartz (DQ12), which elicited an increased (pro
      )inflammatory response, as reported in vivo. At the administrated MWCNT doses
      relevant to human occupational lifetime exposure (10 MUg/cm2 for 5 weeks of
      repeated exposures/5 days per week) elevated cilia beating frequency (in both
      epithelial cultures), and mucociliary clearance (in asthmatic cells only)
      occurred, whereas no cytotoxic reactions or morphological changes were observed.
      However, chronic MWCNT exposure did induce an evident (pro-)inflammatory and
      oxidative stress response in both healthy and asthmatic cells. The latter
      revealed stronger and more durable long-term effects compared to healthy cells,
      indicating that individuals with asthma may be more susceptible to adverse
      effects from chronic MWCNT exposure. Our results highlight the power of
      occupationally relevant subchronic exposures on human in vitro models in
      nanosafety hazard assessment.

PMID- 28505410
TI  - New Prodigiosin Derivatives Obtained by Mutasynthesis in Pseudomonas putida.
AB  - The deeply red-colored natural compound prodigiosin is a representative of the
      prodiginine alkaloid family, which possesses bioactivities as antimicrobial,
      antitumor, and antimalarial agents. Various bacteria including the opportunistic
      human pathogen Serratia marcescens and different members of the Streptomycetaceae
      and Pseudoalteromonadaceae produce prodiginines. In addition, these microbes
      generally accumulate many structurally related alkaloids making efficient
      prodiginine synthesis and purification difficult and expensive. Furthermore, it
      is known that structurally different natural prodiginine variants display
      differential bioactivities. In the herein described mutasynthesis approach, 13
      different derivatives of prodigiosin were obtained utilizing the GRAS (generally
      recognized as safe) classified strain Pseudomonas putida KT2440. Genetic
      engineering of the prodigiosin pathway together with incorporation of synthetic
      intermediates thus resulted in the formation of a so far unprecedented structural
      diversity of new prodiginine derivatives in P. putida. Furthermore, the formed
      products allow reliable conclusions regarding the substrate specificity of PigC,
      the final condensing enzyme in the prodigiosin biosynthesis pathway of S.
      marcescens. The biological activity of prodigiosin toward modulation of autophagy
      was preserved in prodiginine derivatives. One prodiginine derivative displayed
      more potent autophagy inhibitory activity than the parent compound or the
      synthetic clinical candidate obatoclax.

PMID- 28505411
TI  - Quantification of Endogenous Cholesterol in Human Serum on Paper Using Direct
      Analysis in Real Time Mass Spectrometry.
AB  - Blood testing for endogenous small metabolites to determine physiological and
      biochemical states is routine for laboratory analysis. Here we demonstrate that
      by combining the commercial direct analysis in real time (DART) ion source with
      an ion trap mass spectrometer, native cholesterol in its free alcohol form is
      readily detected from a few hundred nanoliters of human serum loaded onto
      chromatography paper. Deuterium-labeled cholesterol was used as the internal
      standard to obtain the absolute quantity of the endogenous cholesterol. The
      amount of the cholesterol measured by this paper-loaded DART mass spectrometry
      (pDART-MS) is statistically comparable with that obtained by using commercially
      available fluorometric-enzymatic assay and liquid chromatography/mass
      spectrometry. Furthermore, sera from 21 participants at three different time
      points in an ultramarathon were collected to obtain their cholesterol levels. The
      test requires only very minimal sample preparation, and the concentrations of
      cholesterol in each sample were acquired within a minute.

PMID- 28505412
TI  - Diffraction-Free Bloch Surface Waves.
AB  - Here, we demonstrate a diffraction-free Bloch surface wave sustained on all
      dielectric multilayers that does not diffract after being passed through three
      obstacles or across a single mode fiber. It can propagate in a straight line for
      distances longer than 110 MUm at a wavelength of 633 nm and could be applied as
      an in-plane optical virtual probe both in air and in an aqueous environment. Its
      ability to be used in water, its long diffraction-free distance, and its
      tolerance to multiple obstacles make this wave ideal for certain applications in
      areas such as the biological sciences, where many measurements are made on glass
      surfaces or for which an aqueous environment is required, and for high-speed
      interconnections between chips, where low loss is necessary.

PMID- 28505414
TI  - Quantitative Online Liquid Chromatography-Surface-Enhanced Raman Scattering (LC
      SERS) of Methotrexate and its Major Metabolites.
AB  - The application of Raman spectroscopy as a detection method coupled with liquid
      chromatography (LC) has recently attracted considerable interest, although this
      has currently been limited to isocratic elution. The combination of LC with
      rapidly advancing Raman techniques, such as surface-enhanced Raman scattering
      (SERS), allows for rapid separation, identification and quantification, leading
      to quantitative discrimination of closely eluting analytes. This study has
      demonstrated the utility of SERS in conjunction with reversed-phase liquid
      chromatography (RP-LC), for the detection and quantification of the
      therapeutically relevant drug molecule methotrexate (MTX) and its metabolites 7
      hydroxy methotrexate (7-OH MTX) and 2,4-diamino-N(10)-methylpteroic acid (DAMPA)
      in pure solutions and mixtures, including spikes into human urine from a healthy
      individual and patients under medication. While the RP-LC analysis developed
      employed gradient elution, where the chemical constituents of the mobile phase
      were modified stepwise during analysis, this did not overtly interfere with the
      SERS signals. In addition, the practicability and clinical utility of this
      approach has also been demonstrated using authentic patients' urine samples.
      Here, the identification of MTX, 7-OH MTX and DAMPA are based on their unique
      SERS spectra, providing limits of detection of 2.36, 1.84, and 3.26 MUM
      respectively. Although these analytes are amenable to LC and LC-MS detection an
      additional major benefit of the SERS approach is its applicability toward the
      detection of analytes that do not show UV absorption or are not ionised for mass
      spectrometry (MS)-based detection. The results of this study clearly demonstrate
      the potential application of online LC-SERS analysis for real-time high
      throughput detection of drugs and their related metabolites in human biofluids.

PMID- 28505413
TI  - Protein Displacement by Herpes Helicase-Primase and the Key Role of UL42 during
      Helicase-Coupled DNA Synthesis by the Herpes Polymerase.
AB  - The herpes helicase-primase (UL5-UL8-UL52) very inefficiently unwinds double
      stranded DNA. To better understand the mechanistic consequences of this
      inefficiency, we investigated protein displacement activity by UL5-UL8-UL52, as
      well as the impact of coupling DNA synthesis by the herpes polymerase with
      helicase activity. While the helicase can displace proteins bound to the lagging
      strand template, bound proteins significantly impede helicase activity.
      Remarkably, UL5-UL8-UL52, an extremely inefficient helicase, disrupts the
      exceptionally tight interaction between streptavidin and biotin on the lagging
      strand template. It also unwinds DNA containing streptavidin bound to the leading
      strand template, although it does not displace the streptavidin. These data
      suggest that the helicase may largely or completely wrap around the lagging
      strand template, with minimal interactions with the leading strand template. We
      utilized synthetic DNA minicircles to study helicase activity coupled with the
      herpes polymerase-processivity factor (UL30-UL42). Coupling greatly enhances
      unwinding of DNA, although bound proteins still inhibit helicase activity.
      Surprisingly, while UL30-UL42 and two noncognate polymerases (Klenow Fragment and
      T4 DNA polymerase) all stimulate unwinding of DNA by the helicase, the isolated
      UL30 polymerase (i.e., no UL42 processivity factor) binds to the replication fork
      but in a manner that is incompetent in terms of coupled helicase-polymerase
      activity.

PMID- 28505415
TI  - Surface-Guided Core-Shell ZnSe@ZnTe Nanowires as Radial p-n Heterojunctions with
      Photovoltaic Behavior.
AB  - The organization of nanowires on surfaces remains a major obstacle toward their
      large-scale integration into functional devices. Surface-material interactions
      have been used, with different materials and substrates, to guide horizontal
      nanowires during their growth into well-organized assemblies, but the only guided
      nanowire heterostructures reported so far are axial and not radial. Here, we
      demonstrate the guided growth of horizontal core-shell nanowires, specifically of
      ZnSe@ZnTe, with control over their crystal phase and crystallographic
      orientations. We exploit the directional control of the guided growth for the
      parallel production of multiple radial p-n heterojunctions and probe their
      optoelectronic properties. The devices exhibit a rectifying behavior with
      photovoltaic characteristics upon illumination. Guided nanowire heterostructures
      enable the bottom-up assembly of complex semiconductor structures with controlled
      electronic and optoelectronic properties.

PMID- 28505416
TI  - High-Temperature-Short-Time Annealing Process for High-Performance Large-Area
      Perovskite Solar Cells.
AB  - Organic-inorganic hybrid metal halide perovskite solar cells (PSCs) are
      attracting tremendous research interest due to their high solar-to-electric power
      conversion efficiency with a high possibility of cost-effective fabrication and
      certified power conversion efficiency now exceeding 22%. Although many effective
      methods for their application have been developed over the past decade, their
      practical transition to large-size devices has been restricted by difficulties in
      achieving high performance. Here we report on the development of a simple and
      cost-effective production method with high-temperature and short-time annealing
      processing to obtain uniform, smooth, and large-size grain domains of perovskite
      films over large areas. With high-temperature short-time annealing at 400 
      degrees C for 4 s, the perovskite film with an average domain size of 1 MUm was
      obtained, which resulted in fast solvent evaporation. Solar cells fabricated
      using this processing technique had a maximum power conversion efficiency
      exceeding 20% over a 0.1 cm2 active area and 18% over a 1 cm2 active area. We
      believe our approach will enable the realization of highly efficient large-area
      PCSs for practical development with a very simple and short-time procedure. This
      simple method should lead the field toward the fabrication of uniform large-scale
      perovskite films, which are necessary for the production of high-efficiency solar
      cells that may also be applicable to several other material systems for more
      widespread practical deployment.

PMID- 28505417
TI  - Hierarchical Chitin Fibers with Aligned Nanofibrillar Architectures: A Nonwoven
      Mat Separator for Lithium Metal Batteries.
AB  - Here, we introduce regenerated fibers of chitin (Chiber), the second most
      abundant biopolymer after cellulose, and propose its utility as a nonwoven fiber
      separator for lithium metal batteries (LMBs) that exhibits an excellent
      electrolyte-uptaking capability and Li-dendrite-mitigating performance. Chiber is
      produced by a centrifugal jet-spinning technique, which allows a simple and fast
      production of Chibers consisting of hierarchically aligned self-assembled chitin
      nanofibers. Following the scrutinization on the Chiber-Li-ion interaction via
      computational methods, we demonstrate the potential of Chiber as a nonwoven mat
      type separator by monitoring it in Li-O2 and Na-O2 cells.

PMID- 28505418
TI  - How Mutations Can Resist Drug Binding yet Keep HIV-1 Protease Functional.
AB  - Human immunodeficiency virus-1 (HIV-1) protease is an important drug target for
      acquired immune deficiency syndrome therapy. Nearly 10 small molecule drugs have
      been approved by the Food and Drug Administration (FDA). However, prolonged use
      of these drugs produced protease mutants that are not susceptible to many of
      these drugs. The mutated proteases, however, continue to cleave the substrate
      peptides and thus remain largely functional. This poses a major challenge for the
      treatment strategies. Thus, it has become imperative to understand how these
      mutations induce drug resistance while maintaining the enzymatic activity of this
      protein. Here, we perform a comprehensive study of the wild type (WT) and
      clinically relevant mutated protease bound to a series of FDA-approved drugs and
      substrates of varying sequences to unravel the mechanism of unhindered activity
      of the drug-resistant protease variants. Our results from large molecular
      dynamics simulations suggest that while binding of the substrate to WT and
      protease mutants involves multiple H-bonding interactions between substrate
      subsites and the protease's main chain atoms, the drug binds primarily through
      the hydrophobic interactions with the side chains of protease's active site and
      flap residues. This implies that any side chain variations caused by mutations in
      protease could greatly modulate the binding affinity of inhibitors, but not of
      the substrates. The significantly weaker free energy of binding of the drugs
      could also be attributed to the limited number of interaction subsites present in
      the inhibitor structures compared to the substrates. These findings in
      combination with the identified protease flap and active site residues that
      contribute to ligand recognition and strong binding can help in the design of
      future resistance-evading HIV-1 protease inhibitors.

PMID- 28505419
TI  - Copper-Zinc-Tin-Sulfide Thin Films via Annealing of Ultrasonic Spray Deposited
      Nanocrystal Coatings.
AB  - Thin polycrystalline films of the solar absorber copper-zinc-tin-sulfide (CZTS)
      were formed by annealing coatings deposited on molybdenum-coated soda lime glass
      via ultrasonic spraying of aerosol droplets from colloidal CZTS nanocrystal
      dispersions. Production of uniform continuous nanocrystal coatings with
      ultrasonic spraying requires that the evaporation time is longer than the aerosol
      flight time from the spray nozzle to the substrate such that the aerosol droplets
      still have low enough viscosity to smooth the impact craters that form on the
      coating surface. In this work, evaporation was slowed by adding a high boiling
      point cosolvent, cyclohexanone, to toluene as the dispersing liquid. We analyzed,
      quantitatively, the effects of the solvent composition on the aerosol and coating
      drying dynamics using an aerosol evaporation model. Annealing coatings in sulfur
      vapor converts them into polycrystalline films with micrometer size grains, but
      the grains form continuous films only when Na is present during annealing to
      enhance grain growth. Continuous films are easier to form when the average
      nanocrystal size is 15 nm: using larger nanocrystals (e.g., 20 nm) sacrifices
      film continuity.

PMID- 28505420
TI  - Immobilization of l-Asparaginase on Carrier Materials: A Comprehensive Review.
AB  - There are two major applications of l-asparaginase (L-ASNase): leukemia therapy
      and the food industry. Especially, its chemotherapeutic effect has attracted
      interest from the scientific community and individual scientists. Therefore, to
      protect the intrinsic activity and half-time of L-ASNase, several carriers and
      immobilization techniques for immobilization of L-ASNase have been described in
      articles. Unfortunately, a comprehensive review about immobilization of L-ASNase
      has not been written until now. In this review, we have thoroughly discussed the
      carriers for L-ASNase by illustrating immobilization findings including both past
      and present applications. In addition, we have revealed advantages and
      disadvantages of immobilized enzyme and related it to free form. We believe that
      this review will not only provide background information, but also guide future
      developments.

PMID- 28505421
TI  - Development of High-Performance Chemical Isotope Labeling LC-MS for Profiling the
      Carbonyl Submetabolome.
AB  - Metabolites containing a carbonyl group represent several important classes of
      molecules including various forms of ketones and aldehydes such as steroids and
      sugars. We report a high-performance chemical isotope labeling (CIL) LC-MS method
      for profiling the carbonyl submetabolome with high coverage and high accuracy and
      precision of relative quantification. This method is based on the use of
      dansylhydrazine (DnsHz) labeling of carbonyl metabolites to change their chemical
      and physical properties to such an extent that the labeled metabolites can be
      efficiently separated by reversed phase LC and ionized by electrospray ionization
      MS. In the analysis of six standards representing different carbonyl classes,
      acetaldehyde could be ionized only after labeling and MS signals were
      significantly increased for other 5 standards with an enhancement factor ranging
      from ~15-fold for androsterone to ~940-fold for 2-butanone. Differential 12C- and
      13C-DnsHz labeling was developed for quantifying metabolic differences in
      comparative samples where individual samples were separately labeled with 12C
      labeling and spiked with a 13C-labeled pooled sample, followed by LC-MS analysis,
      peak pair picking, and peak intensity ratio measurement. In the replicate
      analysis of a 1:1 12C-/13C-labeled human urine mixture (n = 6), an average of
      2030 +/- 39 pairs per run were detected with 1737 pairs in common, indicating the
      possibility of detecting a large number of carbonyl metabolites as well as high
      reproducibility of peak pair detection. The average RSD of the peak pair ratios
      was 7.6%, and 95.6% of the pairs had a RSD value of less than 20%, demonstrating
      high precision for peak ratio measurement. In addition, the ratios of most peak
      pairs were close to the expected value of 1.0 (e.g., 95.5% of them had ratios of
      between 0.67 and 1.5), showing the high accuracy of the method. For metabolite
      identification, a library of DnsHz-labeled standards was constructed, including
      78 carbonyl metabolites with each containing MS, retention time (RT), and MS/MS
      information. This library and an online search program for labeled carbonyl
      metabolite identification based on MS, RT, and MS/MS matches have been
      implemented in a freely available Website, www.mycompoundid.org . Using this
      library, out of the 1737 peak pairs detected in urine, 33 metabolites were
      positively identified. In addition, 1333 peak pairs could be matched to the
      metabolome databases with most of them belonging to the carbonyl metabolites.
      These results show that 12C-/13C-DnsHz labeling LC-MS is a useful tool for
      profiling the carbonyl submetabolome of complex samples with high coverage.

PMID- 28505423
TI  - Simple Inkjet Process To Fabricate Microstructures of Chitinous Nanocrystals for
      Cell Patterning.
AB  - Structural polysaccharide nanocrystals (NCs) including cellulose nanocrystal have
      attracted attention. In order to broaden the range of application of the NCs, we
      can take advantage of their original characteristics by establishing simple and
      reasonable processing methods. We here demonstrate a micropatterning of animal
      cellular adhesion by inkjet printing of aqueous dispersions of cytocompatible
      chitinous NCs onto cellophane films. We display how to regulate the deposition
      form and two-dimensional shape of the chitinous NC micromoldings using a research
      inkjet printer. Adhesive capability of mouse fibroblasts onto the chitinous
      substrates was greatly improved by alkali deacetylation. The deacetylated
      products remained rod-like nanostructures, but the original chitin crystal form
      changed to that of chitosan by an intensive deacetylation. The adhered cells
      could be recovered glycolytically. The chitinous micropatterning substrates can
      be utilized for biomedical applications such as controlling of cellular shapes,
      precise monitoring molecular events in biochemistry, and drug screening.

PMID- 28505422
TI  - Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica
      Nanoparticles.
AB  - Oxygen homeostasis is important in the regulation of biological function. Disease
      progression can be monitored by measuring oxygen levels, thus producing
      information for the design of therapeutic treatments. Noninvasive measurements of
      tissue oxygenation require the development of tools with minimal adverse effects
      and facile detection of features of interest. Fluorine magnetic resonance imaging
      (19F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for
      anatomical imaging, cell tracking, and oxygen sensing. However, the highly
      hydrophobic and lipophobic properties of perfluorocarbons require the formation
      of emulsions for biological studies, though stabilizing these emulsions has been
      challenging. To enhance the stability and biological loading of perfluorocarbons,
      one option is to incorporate perfluorocarbon liquids into the internal space of
      biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon
      loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19F MRI
      detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles
      (UMNs) have large internal cavities (average = 1.8 cm3 g-1), facilitating an
      average 17% loading efficiency of PFCs, meeting the threshold fluorine
      concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs
      have the highest equivalent nuclei per PFC molecule and a spin-lattice (T1)
      relaxation-based oxygen sensitivity of 0.0032 mmHg-1 s-1 at 16.4 T. The option of
      loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell
      syntheses, allows for use of a broad range of PFC liquids from a single material.
      The biocompatible and tunable chemistry of UMNs combined with the intrinsic
      properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical
      imaging, cell tracking, and metabolic spectroscopy with improved stability.

PMID- 28505424
TI  - Addressing the Issue of Microplastics in the Wake of the Microbead-Free Waters
      Act-A New Standard Can Facilitate Improved Policy.
AB  - The United States Microbead-Free Waters Act was signed into law in December 2015.
      It is a bipartisan agreement that will eliminate one preventable source of
      microplastic pollution in the United States. Still, the bill is criticized for
      being too limited in scope, and also for discouraging the development of
      biodegradable alternatives that ultimately are needed to solve the bigger issue
      of plastics in the environment. Due to a lack of an acknowledged, appropriate
      standard for environmentally safe microplastics, the bill banned all plastic
      microbeads in selected cosmetic products. Here, we review the history of the
      legislation and how it relates to the issue of microplastic pollution in general,
      and we suggest a framework for a standard (which we call "Ecocyclable") that
      includes relative requirements related to toxicity, bioaccumulation, and
      degradation/assimilation into the natural carbon cycle. We suggest that such a
      standard will facilitate future regulation and legislation to reduce pollution
      while also encouraging innovation of sustainable technologies.

PMID- 28505425
TI  - Refined Crystal Structure of Samia cynthia ricini Silk Fibroin Revealed by Solid
      State NMR Investigations.
AB  - Samia cynthia ricini is one of the wild silkworms and its silk fibroin (SF)
      consists of alternatively repeating poly-l-alanine (PLA) sequences as crystalline
      domain and glycine-rich sequences as noncrystalline domain; the structure is
      similar to those of spider silk and other wild silkworm silks. In this paper, we
      proposed a new staggered model for the packing arrangement of the PLA sequence
      through the use of the Cambridge Serial Total Energy Package program and a
      comparison of the observed and calculated chemical shifts of the PLA sequence
      with the Gauge Including Projector Augmented Wave method. The new model was
      supported by the interatomic distance information from the cross peaks of Ala
      Cbeta dipolar-assisted rotational resonance (DARR) spectrum of the PLA sequences
      in S. c. ricini SF fiber. In addition, three 13C NMR peaks observed in the beta
      sheet region were assigned to the carbons with different environments in the same
      model, but not assigned to different beta-sheet structures.

PMID- 28505426
TI  - Tuning the Shell Number of Multishelled Metal Oxide Hollow Fibers for Optimized
      Lithium-Ion Storage.
AB  - Searching the long-life transition-metal oxide (TMO)-based materials for future
      lithium-ion batteries (LIBs) is still a great challenge because of the mechanical
      strain resulting from volume change of TMO anodes during the
      lithiation/delithiation process. To well address this challenging issue, we
      demonstrate a controlled method for making the multishelled TMO hollow
      microfibers with tunable shell numbers to achieve the optimal void for efficient
      lithium-ion storage. Such a particularly designed void can lead to a short
      diffusion distance for fast diffusion of Li+ ions and also withstand a large
      volume variation upon cycling, both of which are the key for high-performance
      LIBs. Triple-shelled TMO hollow microfibers are a quite stable anode material for
      LIBs with high reversible capacities (NiO: 698.1 mA h g-1 at 1 A g-1; Co3O4:
      940.2 mA h g-1 at 1 A g-1; Fe2O3: 997.8 mA h g-1 at 1 A g-1), excellent rate
      capability, and stability. The present work opens a way for rational design of
      the void of multiple shells in achieving the stable lithium-ion storage through
      the biomass conversion strategy.

PMID- 28505427
TI  - Modification of Sialic Acids on Solid Phase: Accurate Characterization of Protein
      Sialylation.
AB  - Sialic acids play many important roles in several physiological and pathological
      processes, including cancers, infection, and blood diseases. Sialic acids are
      fragile and prone to fragmentation under electrospray ionization and matrix
      assisted laser desorption/ionization. It is crucial to modify sialic acids for
      qualitative and quantitative identification of their change in abundance in
      complex biological samples. Permethylation is a method of choice for sialic acid
      stabilization, but the harsh conditions during permethylation may lead to the
      decomposition of O-acetyl groups. Esterification or amidation in solution
      effectively protects sialic acids, yet it is not trivial to purify glycans from
      their reagents. Quantitative analysis of glycans can be achieved by labeling
      their reducing end using fluorescent tags. Loss of sialic acids during labeling
      is a major concern. In this study, we demonstrated the utility of sialic acids
      modification for the analysis of sialyl oligosaccharides and glycopeptides.
      Without modification, sialic acids are partially or completely lost during sample
      preparation, leading to the presence of false glycans or glycopeptides in the
      sample. The stabilized sialic acids not only result in accurate identification of
      sialylated glycans but also improve the characterization of intact glycopeptides.
      The modification of sialic acids on the solid support facilitates analysis of
      glycans and their intact glycoproteins.

PMID- 28505428
TI  - Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in
      C1 Domains.
AB  - Conserved homology-1 (C1) domains are peripheral membrane domains that target
      their host proteins to diacylglycerol (DAG)-containing membranes. It has been
      previously shown that a conservative aromatic mutation of a single residue in the
      C1 domain has a profound effect on DAG affinity. We report that the "DAG
      toggling" mutation changes the conformational dynamics of the loop region that
      forms the binding site for the C1 activators. Moreover, there is a correlation
      among the residue identity at the mutation site, DAG affinity, and loop dynamics
      in four C1 variants. We propose that "toggling" of DAG affinity may occur through
      modulation of both protein-membrane interactions and the geometry of the
      activator-binding cleft, with the loop dynamics being responsible for the latter.

PMID- 28505431
TI  - Stepping Library-Based Post-SELEX Strategy Approaching to the Minimized Aptamer
      in SPR.
AB  - When evolved from SELEX (systematic evolution of ligands by exponential
      enrichment), aptamers are generally about 70-130 nucleotides in length and needed
      to be effectively truncated for further diagnosis or therapeutic uses. Post-SELEX
      optimization is then aroused to simplify the aptamer sequence and improve the
      affinity property. In this work, we report a new post-SELEX strategy based on a
      stepping library for the first time. With a hypothesis that one nucleobase can
      influence the whole binding affinity through its adjacent base stacking and
      potential steric hydrogen bonding interaction, we designed a stepping library
      composed of all probable nucleotide truncation directions. We employed an aptamer
      807-39nt toward EPO-alpha as a model, and surface plasmon resonance (SPR) as an
      efficient screening and evaluation method to optimize all label-free sequences in
      the library. We have successfully picked out In27 as the minimized aptamer from a
      mini library of only 35 sequences. Aptamer In27 has a sole loop, without the
      original stem portion of the initial aptamer, but retains the whole binding
      affinity. We have also defined the key nucleotide contribution by site
      mutagenesis with natural bases, and finally produced a degenerated sequence with
      higher or the same good affinities. Furthermore, we explored different binding
      behaviors between aptamer In27 and other recognition molecule such as agglutinin,
      monoclonal antibody, or receptor by competition or binding assays. Our work
      provides a new and efficient post-SELEX optimization strategy, as well as a
      minimized aptamer In27 with an explicit degenerated sequence and a defined
      binding behavior. That would enhance their great potential in future diagnosis
      and therapy.

PMID- 28505430
TI  - Proteins and Amino Acids in Fine Particulate Matter in Rural Guangzhou, Southern
      China: Seasonal Cycles, Sources, and Atmospheric Processes.
AB  - Water-soluble proteinaceous matter including proteins and free amino acids (FAAs)
      as well as some other chemical components was analyzed in fine particulate matter
      (PM2.5) samples collected over a period of one year in rural Guangzhou. Annual
      averaged protein and total FAAs concentrations were 0.79 +/- 0.47 MUg m-3 and
      0.13 +/- 0.05 MUg m-3, accounting for 1.9 +/- 0.7% and 0.3 +/- 0.1% of PM2.5,
      respectively. Among FAAs, glycine was the most abundant species (19.9%), followed
      by valine (18.5%), methionine (16.1%), and phenylalanine (13.5%). Both proteins
      and FAAs exhibited distinct seasonal variations with higher concentrations in
      autumn and winter than those in spring and summer. Correlation analysis suggests
      that aerosol proteinaceous matter was mainly derived from intensive agricultural
      activities, biomass burning, and fugitive dust/soil resuspension. Significant
      correlations between proteins/FAAs and atmospheric oxidant (O3) indicate that
      proteins/FAAs may be involved in O3 related atmospheric processes. Our
      observation confirms that ambient FAAs could be degraded from proteins under the
      influence of O3, and the stoichiometric coefficients of the reactions were
      estimated for FAAs and glycine. This finding provides a possible pathway for the
      production of aerosol FAAs in the atmosphere, which will improve the current
      understanding on atmospheric processes of proteinaceous matter.

PMID- 28505429
TI  - Control of the Yeast Mating Pathway by Reconstitution of Functional alpha-Factor
      Using Split Intein-Catalyzed Reactions.
AB  - Synthetic control strategies using signaling peptides to regulate and coordinate
      cellular behaviors in multicellular organisms and synthetic consortia remain
      largely underdeveloped because of the complexities necessitated by heterologous
      peptide expression. Using recombinant proteins that exploit split intein-mediated
      reactions, we presented here a new strategy for reconstituting functional
      signaling peptides capable of eliciting desired cellular responses in S.
      cerevisiae. These designs can potentially be tailored to any signaling peptides
      to be reconstituted, as the split inteins are promiscuous and both the peptides
      and the reactions are amenable to changes by directed evolution and other protein
      engineering tools, thereby offering a general strategy to implement synthetic
      control strategies in a large variety of applications.

PMID- 28505432
TI  - Development of a New Extraction Device Based on Parallel-Electromembrane
      Extraction.
AB  - A new device for parallel-electromembrane extraction (Pa-EME) was developed to
      enable simultaneous and high-throughput extraction of ionic and ionizable
      compounds from biofluids. The new system is composed of a reusable conductive
      well-plate used as an acceptor compartment and a filtration well-plate used as a
      donor compartment. A design of experiments was implemented to optimize the main
      experimental parameters (agitation, voltage, and time) with standard solutions in
      formic acid 50 mM. The stirring rate was found the primary influent parameter.
      The Pa-EME device showed excellent extraction yields from 84% to 101% with RSD
      lower than 7.5% on model compounds. Optimized parameters were then applied to
      plasma samples and process efficiencies from 59% to 62% and RSD of less than 8.0%
      were obtained. The whole extraction process took less than 20 min to prepare 8
      samples simultaneously, greatly enhancing the sample preparation throughput (<3
      min per sample).

PMID- 28505433
TI  - Do Environmental Fluoride Exposure and ESRalpha Genetic Variation Modulate
      Methylation Modification on Bone Changes in Chinese Farmers?
AB  - Although increasing evidence suggests that estrogen receptor alpha (ESRalpha)
      genetic variation could modify bone damage caused by environmental fluoride
      exposure, little is known about epigenetic mechanisms in relation to bone
      changes. A case-control study was conducted among farmers aged 18-55 years in
      Henan Province, China. X-ray was used to detect bone changes. Methylation status
      was determined by methylation-specific PCR. Genotypes were identified by Taqman
      probe and real-time PCR. In this study, we found that methylation status in the
      promoter region of the ESRalpha gene was lower in bone change cases than that in
      controls, which was only observed in male farmers after stratification by gender.
      Furthermore, methylation level was negatively associated with the urinary
      fluoride concentration in male farmers. No significant association was found
      between the distribution of ESRalpha rs2941740 genotypes and the risk of bone
      changes. Multivariate logistic regression analysis showed that after adjusting
      for age and gender, increased serum calcium and methylation status were
      protective factors for bone changes. No interaction effect was observed between
      fluoride exposure and ESRalpha rs2941740 polymorphism on bone changes. In
      conclusion, the current work suggests that bone changes are associated with
      methylation status, which might be modulated by fluoride exposure in male
      farmers. Methylation status and bone changes were not modified by ESRalpha gene
      rs2941740 polymorphism in the promoter region.

PMID- 28505434
TI  - Photolysis of Particulate Nitrate as a Source of HONO and NOx.
AB  - Photolysis of nitric acid on the surface has been found recently to be greatly
      enhanced from that in the gas phase. Yet, photolysis of particulate nitrate
      (pNO3) associated with atmospheric aerosols is still relatively unknown. Here,
      aerosol filter samples were collected both near the ground surface and throughout
      the troposphere on board the NSF/NACR C-130 aircraft. The photolysis rate
      constants of pNO3 were determined from these samples by directly monitoring the
      production rates of nitrous acid (HONO) and nitrogen dioxide (NO2) under UV light
      (>290 nm) irradiation. Scaled to the tropical noontime condition on the ground
      level (solar zenith angle = 0 degrees ), the normalized photolysis rate constants
      (jpNO3N) are in the range from 6.2 * 10-6 s-1 to 5.0 * 10-4 s-1 with a median of
      8.3 * 10-5 s-1 and a mean (+/-1 SD) of (1.3 +/- 1.2) * 10-4 s-1. Chemical
      compositions, specifically nitrate loading and organic matter, affect the rate of
      photolysis. Extrapolated to ambient pNO3 loading conditions, e.g. <= 10 nmol m-3,
      the mean jpNO3N value is over 1.8 * 10-4 s-1 in the suburban, rural, and remote
      environments. Photolysis of particulate nitrate is thus a source of HONO and NO2
      in the troposphere.

PMID- 28505436
TI  - Control of Heme Coordination and Catalytic Activity by Conformational Changes in
      Peptide-Amphiphile Assemblies.
AB  - Self-assembling peptide materials have gained significant attention, due to well
      demonstrated applications, but they are functionally underutilized. To advance
      their utility, we use noncovalent interactions to incorporate the biological
      cofactor heme-B for catalysis. Heme-proteins achieve differing functions through
      structural and coordinative variations. Here, we replicate this phenomenon by
      highlighting changes in heme reactivity as a function of coordination, sequence,
      and morphology (micelles versus fibers) in a series of simple peptide amphiphiles
      with the sequence c16-xyL3K3-CO2H where c16 is a palmitoyl moiety and xy
      represents the heme binding region: AA, AH, HH, and MH. The morphology of this
      peptide series is characterized using transmission electron and atomic force
      microscopies as well as dynamic light scattering. Within this small library of
      peptide constructs, we show that three spectroscopically (UV/visible and electron
      paramagnetic resonance) distinct heme environments were generated:
      noncoordinated/embedded high-spin, five-coordinate high-spin, and six-coordinate
      low-spin. The resulting material's functional dependence on sequence and
      supramolecular morphology is highlighted 2-fold. First, the heme active site
      binds carbon monoxide in both micelles and fibers, demonstrating that the heme
      active site in both morphologies is accessible to small molecules for catalysis.
      Second, peroxidase activity was observed in heme-containing micelles yet was
      significantly reduced in heme-containing fibers. We briefly discuss the
      implications these findings have in the production of functional, self-assembling
      peptide materials.

PMID- 28505437
TI  - Heteroaggregation of Graphene Oxide with Nanometer- and Micrometer-Sized Hematite
      Colloids: Influence on Nanohybrid Aggregation and Microparticle Sedimentation.
AB  - Heteroaggregation of graphene oxide (GO) with nanometer- and micrometer-sized
      hematite colloids, which are naturally present in aquatic systems, is
      investigated in this study. The heteroaggregation rates between GO and hematite
      nanoparticles (HemNPs) were quantified by dynamic light scattering, while the
      heteroaggregation between GO and micrometer-sized hematite particles (HemMPs) was
      examined through batch adsorption and sedimentation experiments. The
      heteroaggregation rates of GO with HemNPs first increased and then decreased with
      increasing GO/HemNP mass concentration ratios. The conformation of GO-HemNP
      heteroaggregates at different GO/HemNP mass concentration ratios was observed
      through transmission electron microscopy imaging. Initially, GO underwent
      heteroaggregation with HemNPs through electrostatic attraction to form primary
      heteroaggregates, which were further bridged by GO to form bigger clusters. At
      high GO/HemNP mass concentration ratios where GO outnumbered HemNPs,
      heteroaggregation resulted in the formation of stable GO-HemNP nanohybrids that
      have a critical coagulation concentration of 308 mM NaCl at pH 5.2. In the case
      of HemMPs, GO adsorbed readily on the microparticles and, at an optimal GO/HemMP
      ratio of ~0.002, the sedimentation of HemMPs was the fastest, most likely because
      of the formation of "electrostatic patches" leading to favorable aggregation of
      the microparticles.

PMID- 28505438
TI  - pH-Responsive Coassembly of Oligo(ethylene glycol)-Coated Gold Nanoparticles with
      External Anionic Polymers via Hydrogen Bonding.
AB  - Stimuli-responsive assembly of gold nanoparticles (AuNPs) with precise control of
      the plasmonic properties, assembly size, and stimuli responsivity has shown
      potential benefits with regard to biosensing devices and drug-delivery systems.
      Here we present a new pH-responsive coassembly system of oligo(ethylene glycol)
      (OEG)-coated AuNPs with anionic polymers as an external mediator via hydrogen
      bonding in water. Hydrogen-bond-driven coassemblies of OEG-AuNPs with
      poly(acrylic acid) (PAA) were confirmed by the monitoring of plasmonic peaks and
      hydrodynamic diameters. In this system, the protonation of anionic polymers on
      change in pH triggered the formation of hydrogen bond between the OEG-AuNPs and
      polymers, providing sensitive pH responsivity. The plasmonic properties and
      assembly size are affected by both the ratio of PAA to AuNPs and the molecular
      weight of PAAs. In addition, the attachment of hydrophobic groups to the surface
      ligand or anionic polymer changed the responsive pH range. These results
      demonstrated that the coassembly with an external mediator via hydrogen bonding
      provides a stimuli-responsive assembly system with tunable plasmonic properties,
      assembly size, and stimuli responsivity.

PMID- 28505439
TI  - Anthropogenic 236U in Danish Seawater: Global Fallout versus Reprocessing
      Discharge.
AB  - This work focuses on the occurrence of 236U in seawater along Danish coasts,
      which is the sole water-exchange region between the North Sea-Atlantic Ocean and
      the Baltic Sea. Seawater collected in 2013 and 2014 were analyzed for 236U (as
      well as 238U and 137Cs). Our results indicate that 236U concentrations in Danish
      seawater are distributed within a relatively narrow range of (3.6-8.2) * 107
      atom/L and, to a certain extent, independent of salinity. 236U/238U atomic ratios
      in Danish seawater are more than 4 times higher than the estimated global fallout
      value of 1* 10-9. The levels of 236U/238U atomic ratios obtained are comparable
      to those reported for the open North Sea and much higher than several other open
      oceans worldwide. This indicates that besides the global fallout input, the
      discharges from the two major European nuclear reprocessing plants are dominating
      sources of 236U in Danish seawater. However, unexpectedly high 236U/238U ratios
      as well as high 236U concentrations were observed at low-salinity locations of
      the Baltic Sea. While this feature might be interpreted as a clue for another
      significant 236U input in the Baltic Sea, it may also be caused by the complexity
      of water currents or slow turnover rate.

PMID- 28505440
TI  - Iterative Reconstruction of Memory Kernels.
AB  - In recent years, it has become increasingly popular to construct coarse-grained
      models with non-Markovian dynamics to account for an incomplete separation of
      time scales. One challenge of a systematic coarse-graining procedure is the
      extraction of the dynamical properties, namely, the memory kernel, from
      equilibrium all-atom simulations. In this article, we propose an iterative method
      for memory reconstruction from dynamical correlation functions. Compared to
      previously proposed noniterative techniques, it ensures by construction that the
      target correlation functions of the original fine-grained systems are reproduced
      accurately by the coarse-grained system, regardless of time step and
      discretization effects. Furthermore, we also propose a new numerical integrator
      for generalized Langevin equations that is significantly more accurate than the
      more commonly used generalization of the velocity Verlet integrator. We
      demonstrate the performance of the above-described methods using the example of
      backflow-induced memory in the Brownian diffusion of a single colloid. For this
      system, we are able to reconstruct realistic coarse-grained dynamics with time
      steps about 200 times larger than those used in the original molecular dynamics
      simulations.

PMID- 28505435
TI  - Fine-Tuning Strain and Electronic Activation of Strain-Promoted 1,3-Dipolar
      Cycloadditions with Endocyclic Sulfamates in SNO-OCTs.
AB  - The ability to achieve predictable control over the polarization of strained
      cycloalkynes can influence their behavior in subsequent reactions, providing
      opportunities to increase both rate and chemoselectivity. A series of new
      heterocyclic strained cyclooctynes containing a sulfamate backbone (SNO-OCTs)
      were prepared under mild conditions by employing ring expansions of silylated
      methyleneaziridines. SNO-OCT derivative 8 outpaced even a difluorinated
      cyclooctyne in a 1,3-dipolar cycloaddition with benzylazide. The various orbital
      interactions of the propargylic and homopropargylic heteroatoms in SNO-OCT were
      explored both experimentally and computationally. The inclusion of these
      heteroatoms had a positive impact on stability and reactivity, where electronic
      effects could be utilized to relieve ring strain. The choice of the heteroatom
      combinations in various SNO-OCTs significantly affected the alkyne geometries,
      thus illustrating a new strategy for modulating strain via remote substituents.
      Additionally, this unique heteroatom activation was capable of accelerating the
      rate of reaction of SNO-OCT with diazoacetamide over azidoacetamide, opening the
      possibility of further method development in the context of chemoselective,
      bioorthogonal labeling.

PMID- 28505441
TI  - Confined Pool-Buried Water-Soluble Nanoparticles from Reverse Micelles.
AB  - With the special nature of confined water pools, reverse micelles (RMs) have
      shown potential for a wide range of applications. However, the inherent water
      insolubility of RMs hinders their further application prospect especially for
      applications related to biology. We present herein the first successful
      transformation of water-insoluble RMs into water-soluble nanoparticles without
      changing the confined aqueous interiors by hydrolysis/aminolysis of arm-cleavable
      interfacial cross-linked reverse micelles formed from diester surfactant 1. The
      unique properties exhibited by the aqueous interiors of the resulting pool-buried
      water-soluble nanoparticles (PWNPs) were demonstrated both by the template
      synthesis of gold nanoparticles in the absence of external reductants and by the
      fluorescence enhancement of encapsulated thioflavin T (ThT). Importantly, the
      unique potential for PWNPs in biological applications was exemplified by the use
      of ThT@PWNPs and "cell targeted" ThT@PWNPs as effective optical imaging agents of
      living cells. This work conceptually overcomes the application bottleneck of RMs
      and opens an entry to a new class of functional materials.

PMID- 28505442
TI  - Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects.
AB  - The increasing understanding of the role of nitric oxide (NO) in cancer biology
      has generated significant progress in the use of NO donor-based therapy to fight
      cancer. These advances strongly suggest the potential adoption of NO donor-based
      therapy in clinical practice, and this has been supported by several clinical
      studies in the past decade. In this review, we first highlight several types of
      important NO donors, including recently developed NO donors bearing a
      dinitroazetidine skeleton, represented by RRx-001, with potential utility in
      cancer therapy. Special emphasis is then given to the combination of NO donor(s)
      with other therapies to achieve synergy and to the hybridization of NO donor(s)
      with an anticancer drug/agent/fragment to enhance the activity or specificity or
      to reduce toxicity. In addition, we briefly describe inducible NO synthase gene
      therapy and nanotechnology, which have recently entered the field of NO donor
      therapy.

PMID- 28505444
TI  - Explicit Incorporation of Hard and Soft Protein-Protein Interactions into Models
      for Crowding Effects in Protein Mixtures. 2. Effects of Varying Hard and Soft
      Interactions upon Prototypical Chemical Equilibria.
AB  - Previously derived approximate analytical relations for the activity coefficient
      of each solute in a mixture of up to three spherical solutes in a highly nonideal
      solution interacting via square well potentials of mean force (Hoppe, T.; Minton,
      A. P. J Phys Chem B. 2016, 120, 11866-11872) were used to explore the effect of
      heterogeneity in volume occupancy and intermolecular interactions upon
      prototypical schemes representing solubility, partitioning, conformational
      isomerization, and self-association in crowded solutions. Results generally
      indicate that all of the equilibria explored are exquisitely sensitive to
      variations in both volume occupancy and intermolecular interaction and have
      important implications for the design and execution of more detailed simulations
      of complex media.

PMID- 28505443
TI  - Defect Antiperovskite Compounds Hg3Q2I2 (Q = S, Se, and Te) for Room-Temperature
      Hard Radiation Detection.
AB  - The high Z chalcohalides Hg3Q2I2 (Q = S, Se, and Te) can be regarded as of
      antiperovskite structure with ordered vacancies and are demonstrated to be very
      promising candidates for X- and gamma-ray semiconductor detectors. Depending on
      Q, the ordering of the Hg vacancies in these defect antiperovskites varies and
      yields a rich family of distinct crystal structures ranging from zero-dimensional
      to three-dimensional, with a dramatic effect on the properties of each compound.
      All three Hg3Q2I2 compounds show very suitable optical, electrical, and good
      mechanical properties required for radiation detection at room temperature. These
      compounds possess a high density (>7 g/cm3) and wide bandgaps (>1.9 eV), showing
      great stopping power for hard radiation and high intrinsic electrical
      resistivity, over 1011 Omega cm. Large single crystals are grown using the vapor
      transport method, and each material shows excellent photo sensitivity under
      energetic photons. Detectors made from thin Hg3Q2I2 crystals show reasonable
      response under a series of radiation sources, including 241Am and 57Co radiation.
      The dimensionality of Hg-Q motifs (in terms of ordering patterns of Hg vacancies)
      has a strong influence on the conduction band structure, which gives the quasi
      one-dimensional Hg3Se2I2 a more prominently dispersive conduction band structure
      and leads to a low electron effective mass (0.20 m0). For Hg3Se2I2 detectors,
      spectroscopic resolution is achieved for both 241Am alpha particles (5.49 MeV)
      and 241Am gamma-rays (59.5 keV), with full widths at half-maximum (FWHM, in
      percentage) of 19% and 50%, respectively. The carrier mobility-lifetime MUtau
      product for Hg3Q2I2 detectors is achieved as 10-5-10-6 cm2/V. The electron
      mobility for Hg3Se2I2 is estimated as 104 +/- 12 cm2/(V.s). On the basis of these
      results, Hg3Se2I2 is the most promising for room-temperature radiation detection.

PMID- 28505445
TI  - Confining Potential as a Function of Polymer Stiffness and Concentration in
      Entangled Polymer Solutions.
AB  - We directly track the tubelike motion of individual fluorescently labeled polymer
      molecules in a concentrated solution of unlabeled polymers. We use a single
      molecule wide-field fluorescence microscopy technique that is able to determine
      characteristic properties of the polymer dynamics, such as the confining
      potential, the tube diameter, and the Rouse time. The use of synthetic polymers
      allows us to investigate the confined motion of the polymer chains not only as a
      function of polymer concentration (mesh size) but also versus the persistence
      length of the matrix polymers. Although the polymers used have a persistence
      length much smaller than their contour length, our experimental results lead to a
      dependence of the tube diameter on both the mesh size and the persistence length,
      which follows the theoretically predicted relation for semiflexible chains.

PMID- 28505446
TI  - Role of the C(2)-H Hydrogen Bond Donor in Gas-Phase Microsolvation of Imidazole
      Derivatives with ROH (R = CH3, C2H5).
AB  - Although the hydrogen-bonding properties of the protic solvents are comparable, a
      comparison of the gas-phase structures of water with those of the alcohols
      reveals certain similarities as well as differences. In this work we report the
      microsolvated clusters of imidazole derivatives, Benzimidazole (BIM) and N
      methylbenzimidazole (MBIM) by methanol (M) and ethanol (E) in supersonic jet
      using electronic and vibrational spectroscopy and compare them with their
      hydrated clusters. The cluster sizes up to 1:2 of BIM/MBIM with methanol and
      ethanol, and up to 1:3 in the case of MBIM-methanol were observed. Both the N
      H...O and O-H...N bound structures were observed for the BIM-M1 and BIM-E1
      complexes. The O-H...N bound structures of 1:1 complexes of MBIM were relatively
      more stable than their BIM counterparts by about ~0.25 kcal mol-1. Three distinct
      conformations (anti, gauche, and gauche') were identified for the O-H...N bound
      complexes of BIM-E1 and MBIM-E1. IR spectroscopy of the doubly and triply
      solvated clusters (namely BIM-M2, MBIM-M2,3 and MBIM-E2) gives unequivocal proof
      of H-bonded bridges that originate from the N acceptor and terminate at the C(2)
      H group, similar to the analogous water clusters. These studies confirm that the
      C(2)-H in imidazole plays an important role in its solvation, particularly in the
      case of polar solvents. Quantum chemical calculations performed at the DFT (B3LYP
      as well as dispersion-corrected functionals) and MP2 levels corroborate the
      experimental findings. Comparison of the QTAIM and NBO parameters for the
      pairwise solvent interactions in the clusters with those of methanol and ethanol
      homodimers reflects the co-operative nature of these H-bonding interactions.

PMID- 28505447
TI  - Interrogating the Roles of Post-Translational Modifications of Non-Histone
      Proteins.
AB  - Post-translational modifications (PTMs) allot versatility to the biological
      functions of highly conserved proteins. Recently, modifications to non-histone
      proteins such as methylation, acetylation, phosphorylation, glycosylation,
      ubiquitination, and many more have been linked to the regulation of pivotal
      pathways related to cellular response and stability. Due to the roles these
      dynamic modifications assume, their dysregulation has been associated with cancer
      and many other important diseases such as inflammatory disorders and
      neurodegenerative diseases. For this reason, we present a review and perspective
      on important post-translational modifications on non-histone proteins, with
      emphasis on their roles in diseases and small molecule inhibitors developed to
      target PTM writers. Certain PTMs' contribution to epigenetics has been
      extensively expounded; yet more efforts will be needed to systematically dissect
      their roles on non-histone proteins, especially for their relationships with
      nononcological diseases. Finally, current research approaches for PTM study will
      be discussed and compared, including limitations and possible improvements.

PMID- 28505448
TI  - Spectroscopic and Calorimetric Studies of Molecular Recognitions in a Dendrimer
      Surfactant Complex.
AB  - Molecular recognitions, causing supramolecular complex formation between a
      hyperbranched polymer molecule (polyamidoamine (PAMAM) dendrimer generation 3)
      with oppositely charged surfactant sodium dodecyl sulfate (SDS) in aqueous
      solution, were studied by using various spectroscopic techniques and calorimetric
      titration of heat change measurements. Spectroscopic measurements were performed
      using dynamic Stokes shift (DSS), rotational anisotropy decay, and translational
      diffusion of a fluorescent probe molecule coumarin 153 (C153) noncovalently
      attached to the dendrimer-surfactant complex. All these studies unanimously
      confirm that the critical aggregation concentration (CAC) of SDS falls to ~0.8 mM
      (from its critical micelle concentration (CMC) ~ 8 mM) in the presence of ~0.2 mM
      dendrimer. Further studies of isothermal titration calorimetry (ITC) measurement
      show that the CAC of SDS in the presence of dendrimer remains invariant to the
      dendrimer concentration. Complexation reaction between SDS and dendrimer is
      highly exothermic in nature. A maximum heat release (DeltaH~ -6.6 kJ/mol of SDS
      binding) was observed at a SDS-to-dendrimer mole ratio of ~3-5; where up to 3 to
      5 SDS molecules were encapsulated by one dendrimer molecule to form dendrimer-SDS
      encapsulation complex. When negatively charged SDS was replaced with a positively
      charged surfactant dodecyl-trimethylammonium-bromide (DTAB), we found that the
      DTAB hardly interacted with positively charged dendrimer due to the charge-charge
      repulsions.

PMID- 28505449
TI  - Interfacial Water Arrangement in the Ice-Bound State of an Antifreeze Protein: A
      Molecular Dynamics Simulation Study.
AB  - Molecular dynamics (MD) simulations have been carried out to study the
      heterogeneous ice nucleation on modeled peptide surfaces. Simulations show that
      large peptide surfaces made by TxT (threonine-x-threonine) motifs with the
      arrangements of threonine (Thr) residues identical to the periodic arrangements
      of waters on either the basal or prism plane of ice are capable of ice
      nucleation. Nucleated ice plane is the (0001) basal plane of hexagonal ice (Ih)
      or (111) plane of cubic ice (Ic). However, due to predefined simulation cell
      dimensions, the ice growth is only observed on the surface where the Thr residues
      are arranged like the water arrangement on the basal plane of ice Ih. The gamma
      methyl and gamma-hydroxyl groups of Thr residue are necessary for such ice
      formation. From this ice nucleation and growth simulation, the interfacial water
      arrangement in the ice-bound state of Tenebrio molitor antifreeze protein (TmAFP)
      has been determined. The interfacial water arrangement in the ice-bound state of
      TmAFP is characterized by five-membered hydrogen bonded rings, where each of the
      hydroxyl groups of the Thr residues on the ice-binding surface (IBS) of the
      protein is a ring member. It is found that the water arrangement at the protein
      ice interface is distorted from that in bulk ice. Our analysis further reveals
      that the hydroxyl groups of Thr residues on the IBS of TmAFP form maximum three
      hydrogen bonds each with the waters in the bound state and methyl groups of Thr
      residues occupy wider spaces than the normal grooves on the (111) plane of ice
      Ic. Methyl groups are also located above and along the 3-fold rotational axes of
      the chair-formed hexagonal hydrogen bonded water rings on the (111) plane.

PMID- 28505450
TI  - Asymmetric Spreading of a Drop upon Impact onto a Surface.
AB  - Study of the spreading of an impacting drop onto a surface has gained importance
      recently due to applications in printing, coating, and icing. Limited studies are
      conducted to understand asymmetric spreading of a drop seen upon drop impact onto
      a moving surface; there is no relation to describe such spreading. Here, we
      experimentally studied the spreading of a drop over a moving surface; such study
      also provides insights for systems where a drop impacts at an angle relative to a
      surface, i.e., drop has both normal and tangential velocities relative to the
      surface. We developed a model that for the first time allows prediction of time
      evolution for the asymmetric shape of the lamella during spreading. The developed
      model is demonstrated to be valid for a range of liquids and surface
      wettabilities as well as drop and surface velocities, making this study a
      comprehensive examination of the topic. We also found out how surface wettability
      can affect the recoil of the drop after spreading and explained the role of
      contact angle hysteresis and receding contact angle in delaying the recoil
      process.

PMID- 28505451
TI  - Toward Successful Cyclodextrin Based Solubility-Enabling Formulations for Oral
      Delivery of Lipophilic Drugs: Solubility-Permeability Trade-Off, Biorelevant
      Dissolution, and the Unstirred Water Layer.
AB  - The purpose of this work was to investigate key factors dictating the
      success/failure of cyclodextrin-based solubility-enabling formulations for oral
      delivery of low-solubility drugs. We have studied the solubility, the
      permeability, and the solubility-permeability interplay, of the highly lipophilic
      drug danazol, formulated with different levels (8.5, 10, 20, and 30%) of the
      commonly used hydroxypropyl-beta-cyclodextrin (HPbetaCD), accounting for the
      biorelevant solubilization of the drug along the gastrointestinal tract (GIT),
      the unstirred water layer (UWL) adjacent to the GI membrane, and the overall
      absorption. HPbetaCD significantly increased danazol solubility, and decreased
      the drugs' permeability, in a concentration-dependent manner. These Peff results
      were in good correlation (R2 = 0.977) to literature rat AUC data of the same
      formulations. Unlike vehicle without HPbetaCD, formulations containing 8.5%
      HPbetaCD and above were shown to successfully dissolve the drug dose during the
      entire biorelevant dissolution experiment. We conclude that CD-based solubility
      enabling formulations should contain the minimal amount of CD sufficient to
      dissolve the drug dose throughout the GIT, and not more than that; excess CD does
      not provide solubility gain but causes further permeability loss, and the overall
      absorption is then impaired. Moreover, a significant UWL effect was revealed in
      danazol intestinal permeability, and accounting for this effect allowed an
      excellent prediction of the solubility-permeability trade-off vs % HPbetaCD.
      Overall, this work assessed the contribution of each individual step of the
      absorption cascade to the success/failure of HPbetaCD-based formulation, allowing
      a more mechanistic development process of better solubility-enabling
      formulations.

PMID- 28505452
TI  - Deposition Patterns of Two Neighboring Droplets: Onsager Variational Principle
      Studies.
AB  - When two droplets containing nonvolatile components are sitting close to each
      other, asymmetrical ring-like deposition patterns are formed on the substrate. We
      propose a simple theory based on the Onsager variational principle to predict the
      deposition patterns of two neighboring droplets. The contact line motion and the
      interference effect of two droplets are considered simultaneously. We demonstrate
      that the gradients of evaporation rate along two droplets is the main reason for
      forming asymmetrical deposition patterns. By tracing the relative motion between
      the contact line and the solute particles, we found that the velocities of solute
      particles have no cylindrical symmetry anymore because of the asymmetrical
      evaporation rate, giving the underlying mechanism of forming asymmetrical
      patterns. Moreover, controlling the evaporation rate combined with varying the
      contact line friction, fan-like and eclipse-like deposition patterns are
      obtained. The theoretical results of pinned contact line cases are qualitatively
      consistent with the pervious experimental results.

PMID- 28505453
TI  - Adaptive and Specific Recognition of Telomeric G-Quadruplexes via Polyvalency
      Induced Unstacking of Binding Units.
AB  - Targeting DNA G-quadruplexes using small-molecule ligands has shown to modulate
      biological functions mediated by G-quadruplexes inside cells. Given >716 000 G
      quadruplex hosting sites in human genome, the specific binding of ligands to
      quadruplex becomes problematic. Here, we innovated a polyvalency based mechanism
      to specifically target multiple telomeric G-quadruplexes. We synthesized a
      tetrameric telomestatin derivative and evaluated its complex polyvalent binding
      with multiple G-quadruplexes by single-molecule mechanical unfolding in laser
      tweezers. We found telomestatin tetramer binds to multimeric telomeric G
      quadruplexes >40 times stronger than monomeric quadruplexes, which can be
      ascribed to the polyvalency induced unstacking of binding units (or PIU binding)
      for G-quadruplexes. While stacking of telomestatin units in the tetramer imparts
      steric hindrance for the ligand to access stand-alone G-quadruplexes, the
      stacking disassembles to accommodate the potent polyvalent binding between the
      tetramer ligand and multimeric G-quadruplexes. We anticipate this adaptive PIU
      binding offers a generic mechanism to selectively target polymeric biomolecules
      prevalent inside cells.

PMID- 28505454
TI  - Perturbation-Response Scanning Reveals Key Residues for Allosteric Control in
      Hsp70.
AB  - Hsp70 molecular chaperones play an important role in maintaining cellular
      homeostasis, and are implicated in a wide array of cellular processes, including
      protein recovery from aggregates, cross-membrane protein translocation, and
      protein biogenesis. Hsp70 consists of two domains, a nucleotide binding domain
      (NBD) and a substrate binding domain (SBD), each of which communicates via an
      allosteric mechanism such that the protein interconverts between two functional
      states, an ATP-bound open conformation and an ADP-bound closed conformation. The
      exact mechanism for interstate conversion is not as yet fully understood.
      However, the ligand-bound states of the NBD and SBD as well as interactions with
      cochaperones such as DnaJ and nucleotide exchange factor are thought to play
      crucial regulatory roles. In this study, we apply the perturbation-response
      scanning (PRS) method in combination with molecular dynamics simulations as a
      computational tool for the identification of allosteric hot residues in the large
      multidomain Hsp70 protein. We find evidence in support of the hypothesis that
      substrate binding triggers ATP hydrolysis and that the ADP-substrate complex
      favors interstate conversion to the closed state. Furthermore, our data are in
      agreement with the proposal that there is an allosterically active intermediate
      state between the open and closed states and vice versa, as we find evidence that
      ATP binding to the closed structure and peptide binding to the open structure
      allosterically "activate" the respective complexes. We conclude our analysis by
      showing how our PRS data fit the current opinion on the Hsp70 conformational
      cycle and present several allosteric hot residues that may provide a platform for
      further studies to gain additional insight into Hsp70 allostery.

PMID- 28505455
TI  - Interaction of Multiple Particles with a Solidification Front: From Compacted
      Particle Layer to Particle Trapping.
AB  - The interaction of solidification fronts with objects such as particles,
      droplets, cells, or bubbles is a phenomenon with many natural and technological
      occurrences. For an object facing the front, it may yield various fates, from
      trapping to rejection, with large implications regarding the solidification
      pattern. However, whereas most situations involve multiple particles interacting
      with each other and the front, attention has focused almost exclusively on the
      interaction of a single, isolated object with the front. Here we address
      experimentally the interaction of multiple particles with a solidification front
      by performing solidification experiments of a monodisperse particle suspension in
      a Hele-Shaw cell with precise control of growth conditions and real-time
      visualization. We evidence the growth of a particle layer ahead of the front at a
      close-packing volume fraction, and we document its steady-state value at various
      solidification velocities. We then extend single-particle models to the situation
      of multiple particles by taking into account the additional force induced on an
      entering particle by viscous friction in the compacted particle layer. By a force
      balance model this provides an indirect measure of the repelling mean
      thermomolecular pressure over a particle entering the front. The presence of
      multiple particles is found to increase it following a reduction of the thickness
      of the thin liquid film that separates particles and front. We anticipate the
      findings reported here to provide a relevant basis to understand many complex
      solidification situations in geophysics, engineering, biology, or food
      engineering, where multiple objects interact with the front and control the
      resulting solidification patterns.

PMID- 28505456
TI  - Self-Polymerization of Dopamine in Acidic Environments without Oxygen.
AB  - An alkaline environment and the presence of oxygen are essential requirements for
      dopamine polymerization. In this study, we are the first to demonstrate the self
      polymerization of dopamine through plasma-activated water (PAW) under acidic
      environments (pH < 5.5). Resulting poly(dopamine) (PDA) was characterized using
      Nanosizer, SEM, FTIR, UV-vis, 1H NMR, and fluorescence spectrophotometers and
      proved to have similar physical and chemical properties to those polymerized
      under a basic condition, except that the PDA particles formed in PAW were more
      stable and hardly aggregated at varied pHs. The PAW polymerization method avoids
      alkaline solutions and the presence of oxygen and thus extends the applications
      of dopamine polymerization, particularly in biomedical and pharmaceutical
      sciences.

PMID- 28505457
TI  - Molecular and Biocompatibility Characterization of Red Blood Cell Membrane
      Targeted and Cell-Penetrating-Peptide-Modified Polymeric Nanoparticles.
AB  - Red blood cells (RBCs) express a variety of immunomodulatory markers that enable
      the body to recognize them as self. We have shown that RBC membrane glycophorin A
      (GPA) receptor can mediate membrane attachment of protein therapeutics. A
      critical knowledge gap is whether attaching drug-encapsulated nanoparticles (NPs)
      to GPA and modification with cell-penetrating peptide (CPP) will impact binding,
      oxygenation, and the induction of cellular stress. The objective of this study
      was to formulate copolymer-based NPs containing model fluorescent-tagged bovine
      serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs),
      single-chain variable antibody (scFv TER-119, SNPs), and low-molecular-weight
      protamine-based CPP (LNPs) and to determine their biocompatibility using a
      variety of complementary high-throughput in vitro assays. Experiments were
      conducted by coincubating NPs with RBCs at body temperature, and biocompatibility
      was evaluated by Raman spectroscopy, hemolysis, complement lysis, and oxidative
      stress assays. Data suggested that LNPs effectively targeted RBCs, conferring 2
      fold greater uptake in RBCs compared to ENPs and SNPs. Raman spectroscopy results
      indicated no adverse effect of NP attachment or internalization on the
      oxygenation status of RBCs. Cellular stress markers such as glutathione,
      malondialdehyde, and catalase were within normal limits, and complement-mediated
      lysis due to NPs was negligible in RBCs. Under the conditions tested, our data
      demonstrates that molecular targeting of the RBC membrane is a feasible
      translational strategy for improving drug pharmacokinetics and that the proposed
      high-throughput assays can prescreen diverse NPs for preclinical and clinical
      biocompatibility.

PMID- 28505458
TI  - Position-Specific 13C Fractionation during Liquid-Vapor Transition Correlated to
      the Strength of Intermolecular Interaction in the Liquid Phase.
AB  - The relationship between the strength of the intermolecular interaction in liquid
      and the position-specific 13C fractionation observed during distillation was
      investigated. A range of molecules showing different intermolecular interactions
      in terms of mode and intensity were incorporated in the study. Although it had
      previously been suggested that during evaporation the diffusive 13C isotope
      effect in the thin liquid layer interfaced with vapor is not position-specific,
      herein we show that this is not the case. In particular, the position-specific
      effect was demonstrated for a series of alcohols. Our hypothesis is that
      intermolecular interactions in the liquid phase are the source of position
      specific 13C fractionation observed on the molecule. A clear trend is observed
      between the 13C isotope effect of the carbon bearing the heteroatom of chemical
      function and the relative permittivity, the solvent hydrogen bond acidity, and
      the solvent hydrogen bond basicity, while only a weak trend was observed when
      using the 13C content of the whole molecule. Furthermore, two families of
      products appeared when using the hydrogen bond acidity parameter for the
      correlation by distinguishing H-acceptor and H-donor molecules from those H
      acceptors only. This strongly reinforces the hypothesis of an important role of
      the 13C positioned close to the interaction center.

PMID- 28505459
TI  - Inhibition of Human Serum Albumin Fibrillation by Two-Dimensional Nanoparticles.
AB  - The formation and deposition of amyloid fibrils have been linked to the
      pathogenesis of numerous debilitating neurodegenerative disorders. Serum albumins
      serve as good model proteins for understanding the molecular mechanisms of
      protein aggregation and fibril formation. Graphene-based nanotherapeutics appear
      to be promising candidates for designing inhibitors of protein fibrillation. The
      inhibitory effect of graphene oxide (GO) nanoparticles on the fibrillation of
      human serum albumin (HSA) in an in vitro mixed solvent system has been
      investigated. The methods used include ThT fluorescence, ANS binding, Trp
      fluorescence, circular dichroism, fluorescence microscopy, field-emission
      scanning electron microscopy, and high-resolution transmission electron
      microscopy. It was observed that GO inhibits HSA fibrillation and forms
      agglomerates with beta-sheet rich prefibrillar species. Binding of GO prevents
      the formation of mature fibrils with characteristic cross-beta sheet but does not
      promote refolding to the native state.

PMID- 28505460
TI  - Thermal Management in Nanofiber-Based Face Mask.
AB  - Face masks are widely used to filter airborne pollutants, especially when
      particulate matter (PM) pollution has become a serious concern to public health.
      Here, the concept of thermal management is introduced into face masks for the
      first time to enhance the thermal comfort of the user. A system of nanofiber on
      nanoporous polyethylene (fiber/nanoPE) is developed where the nanofibers with
      strong PM adhesion ensure high PM capture efficiency (99.6% for PM2.5) with low
      pressure drop and the nanoPE substrate with high-infrared (IR) transparency
      (92.1%, weighted based on human body radiation) results in effective radiative
      cooling. We further demonstrate that by coating nanoPE with a layer of Ag, the
      fiber/Ag/nanoPE mask shows a high IR reflectance (87.0%) and can be used for
      warming purposes. These multifunctional face mask designs can be explored for
      both outdoor and indoor applications to protect people from PM pollutants and
      simultaneously achieve personal thermal comfort.

PMID- 28505461
TI  - Spatial-Temporal Imaging of Anisotropic Photocarrier Dynamics in Black
      Phosphorus.
AB  - As an emerging single elemental layered material with a low symmetry in-plane
      crystal lattice, black phosphorus (BP) has attracted significant research
      interest owing to its unique electronic and optoelectronic properties, including
      its widely tunable bandgap, polarization-dependent photoresponse and highly
      anisotropic in-plane charge transport. Despite extensive study of the steady
      state charge transport in BP, there has not been direct characterization and
      visualization of the hot carriers dynamics in BP immediately after
      photoexcitation, which is crucial to understanding the performance of BP-based
      optoelectronic devices. Here we use the newly developed scanning ultrafast
      electron microscopy (SUEM) to directly visualize the motion of photoexcited hot
      carriers on the surface of BP in both space and time. We observe highly
      anisotropic in-plane diffusion of hot holes with a 15 times higher diffusivity
      along the armchair (x-) direction than that along the zigzag (y-) direction. Our
      results provide direct evidence of anisotropic hot carrier transport in BP and
      demonstrate the capability of SUEM to resolve ultrafast hot carrier dynamics in
      layered two-dimensional materials.

PMID- 28505462
TI  - Giant Gating Tunability of Optical Refractive Index in Transition Metal
      Dichalcogenide Monolayers.
AB  - We report that the refractive index of transition metal dichacolgenide (TMDC)
      monolayers, such as MoS2, WS2, and WSe2, can be substantially tuned by >60% in
      the imaginary part and >20% in the real part around exciton resonances using
      complementary metal-oxide-semiconductor (CMOS) compatible electrical gating. This
      giant tunablility is rooted in the dominance of excitonic effects in the
      refractive index of the monolayers and the strong susceptibility of the excitons
      to the influence of injected charge carriers. The tunability mainly results from
      the effects of injected charge carriers to broaden the spectral width of
      excitonic interband transitions and to facilitate the interconversion of neutral
      and charged excitons. The other effects of the injected charge carriers, such as
      renormalizing bandgap and changing exciton binding energy, only play negligible
      roles. We also demonstrate that the atomically thin monolayers, when combined
      with photonic structures, can enable the efficiencies of optical absorption
      (reflection) tuned from 40% (60%) to 80% (20%) due to the giant tunability of the
      refractive index. This work may pave the way toward the development of field
      effect photonics in which the optical functionality can be controlled with CMOS
      circuits.

PMID- 28505464
TI  - Treatment of the cardiac hypertrophic response and heart failure with ginseng,
      ginsenosides, and ginseng-related products.
AB  - Heart failure is a major medical and economic burden throughout the world.
      Although various treatment options are available to treat heart failure, death
      rates in both men and women remain high. Potential adjunctive therapies may lie
      with use of herbal medications, many of which possess potent pharmacological
      properties. Among the most widely studied is ginseng, a member of the genus Panax
      that is grown in many parts of the world and that has been used as a medical
      treatment for a variety of conditions for thousands of years, particularly in
      Asian societies. There are a number of ginseng species, each possessing distinct
      pharmacological effects due primarily to differences in their bioactive
      components including saponin ginsenosides and polysaccharides. While experimental
      evidence for salutary effects of ginseng on heart failure is robust, clinical
      evidence is less so, primarily due to a paucity of large-scale well-controlled
      clinical trials. However, there is evidence from small trials that ginseng
      containing Chinese medications such as Shenmai can offer benefit when
      administered as adjunctive therapy to heart failure patients. Substantial
      additional studies are required, particularly in the clinical arena, to provide
      evidence for a favourable effect of ginseng in heart failure patients.

PMID- 28505465
TI  - Isomerization of glucose into fructose by environmentally friendly Fe/beta
      zeolite catalysts.
AB  - Herein, the environmentally friendly Fe/beta zeolite for glucose isomerization to
      fructose in aqueous media was reported for the first time. The effects of various
      reaction conditions including reaction temperature, reaction time, catalyst
      dosage, etc. on the isomerization reaction over Fe/beta zeolite were studied in
      detail. Under the optimized conditions, yield of fructose higher than 20% were
      obtained. Moreover, the Fe/beta zeolite catalysts were stable and remained
      constant catalytic activity after five consecutive runs. The possible active Fe
      species for isomerization of glucose in Fe/beta zeolite is also discussed.

PMID- 28505463
TI  - In Vivo Pretargeted Imaging of HER2 and TAG-72 Expression Using the HaloTag
      Enzyme.
AB  - A novel pretargeted SPECT imaging strategy based on the HaloTag enzyme has been
      evaluated for the first time in a living system. To determine the efficacy of
      this approach, two clinically relevant cancer biomarkers, HER2 and TAG-72, were
      selected to represent models of internalizing and noninternalizing antigens,
      respectively. In MDA-MB-231/H2N (HER2-expressing) and LS174T (TAG-72-expressing)
      xenograft tumors in mice, pretargeting experiments were performed in which
      HaloTag-conjugated derivatives of the antibodies trastuzumab (anti-HER2) or CC49
      (anti-TAG-72) were utilized as primary agents, and the small molecule HaloTag
      ligands 111In-HTL-1, -2, and -3 were evaluated as secondary agents. While this
      approach was not sufficiently sensitive to detect the internalizing HER2 antigen,
      pretargeting experiments involving the most optimal secondary agent, 111In-HTL-3,
      were successful in detecting the noninternalizing antigen TAG-72 and provided
      high-contrast SPECT images at 4 and 24 h postinjection.

PMID- 28505466
TI  - The conceptualization of emotion regulation difficulties, and its association
      with posttraumatic stress symptoms in traumatized refugees.
AB  - This study investigated the conceptualization of emotion regulation difficulties
      in a sample of refugees with varying levels of posttraumatic stress (PTS), and
      examined whether specific emotion regulation difficulties were associated with
      PTS severity. Refugees were administered an abbreviated version of the
      Difficulties in Emotion Regulation Scale, the PTSD Symptom Scale - Interview
      Version, and the Harvard Trauma Questionnaire. Confirmatory Factor Analysis was
      used to examine model fit for the 6-factor model originally proposed by the
      developers of the DERS and the more recently proposed 5-factor model that
      excludes the awareness subscale. Both models displayed adequate fit. After
      controlling for age, gender, time in Australia, and trauma exposure, the clarity
      and strategies subscales were significantly associated with PTS severity. The
      association between impaired emotional clarity and reduced agency related to
      accessing regulation strategies and PTS severity in this refugee sample
      highlights the need for further research to assess interventions that target
      these disruptions in refugees.

PMID- 28505467
TI  - Low cholesterol level as a risk marker of inpatient and post-discharge violence
      in acute psychiatry - A prospective study with a focus on gender differences.
AB  - Several studies indicate an association between low levels of serum cholesterol
      and aggressive behaviour, but prospective studies are scarce. In this
      naturalistic prospective inpatient and post-discharge study from an acute
      psychiatric ward, we investigated total cholesterol (TC) and high-density
      lipoprotein (HDL) as risk markers of violence. From March 21, 2012, to March 20,
      2013, 158 men and 204 women were included. TC and HDL were measured at admission.
      Violence was recorded during hospital stay and for the first 3 months post
      discharge. Univariate and multivariate binary logistic regression were used to
      estimate associations between low TC and low HDL and violence. Results showed
      that HDL level was significantly inversely associated with violence during
      hospital stay for all patients. For men, but not for women, HDL level was
      significantly inversely associated with violence the first 3 months post
      discharge. Results indicate that low HDL is a risk marker for inpatient and post
      discharge violence in acute psychiatry and also suggest gender differences in HDL
      as a risk marker for violence.

PMID- 28505468
TI  - Comparison of insight and clinical variables in homeless and non-homeless
      psychiatric inpatients in China.
AB  - There are no published data on insight in homeless patients with psychiatric
      disorders in China. This study examined insight in homeless and non-homeless
      Chinese psychiatric inpatients in relation to demographic and clinical variables.
      A total of 278 homeless and 222 non-homeless inpatients matched in age and gender
      were included in the study. Demographic and clinical characteristics were
      collected based on a review of medical charts and a clinical interview with
      standardized instruments. Insight was evaluated with the Insight and Treatment
      Attitudes Questionnaire. Altogether 20.5% of homeless inpatients and 43.7% of the
      non-homeless controls had good insight. Compared with homeless inpatients with
      impaired insight, homeless inpatients with good insight had higher physical
      quality of life, longer duration of illness and less severe positive and negative
      symptoms. Impaired insight appeared more common in homeless psychiatric
      inpatients in China. Further studies should address the need for effective
      therapeutic interventions that promote homeless patients' insight.

PMID- 28505469
TI  - The association between immune markers and recent suicide attempts in patients
      with serious mental illness: A pilot study.
AB  - Previous studies have identified elevations in markers of gastrointestinal
      inflammation in schizophrenia and mood disorders but studies have not measured
      the association between these markers and recent suicide attempts. We assessed
      210 patients receiving treatment for schizophrenia, bipolar disorder, or major
      depression. We employed the Columbia Suicide Severity Rating Scale to identify
      recent and lifetime suicide attempts (actual, aborted, and interrupted).
      Psychiatric participants and a control group of 72 individuals without a
      psychiatric disorder had a blood sample drawn from which were measured specific
      markers of gastrointestinal inflammation and also C-Reactive protein (CRP). A
      total of 20 (10%) of psychiatric participants had a suicide attempt in the
      previous one month and 95 (45%) an attempt during their lifetime but not in the
      previous one month. The recent attempters had significantly elevated levels of
      antibodies to yeast mannan from Saccharomyces cerevisiae (ASCA), the food antigen
      gliadin, and bacterial lipopolysaccharide (LPS) compared with the non-psychiatric
      group when adjusting for demographic and clinical variables. These markers were
      not elevated in individuals with a past, but not recent, suicide attempt history.
      Our study indicates that there is evidence of gastrointestinal inflammation in
      some individuals who have had a recent suicide attempt.

PMID- 28505471
TI  - A prospective examination of risk factors in the development of intrusions
      following a trauma analog.
AB  - Several factors have been linked to the severity of posttraumatic distress,
      although retrospective designs in much of the literature limit conclusions
      regarding the temporal relation between risk factors and corresponding symptoms.
      To address these concerns, the current project employed an analog trauma paradigm
      to assess the impact of background characteristics, stress response, and post
      stressor affect regulation on subjective distress and intrusive memories
      experienced during the subsequent processing of emotional stimuli. University
      students (N = 184; 56% female, 42% White/Non-Hispanic) were shown graphic scenes
      of a televised suicide. Physiological activation was recorded during exposure
      with emotion ratings collected following the film. Participants then viewed a
      sadness- or humor-eliciting prime under instructions to inhibit or naturally
      express emotion. Intrusions experienced during the priming film and residual
      distress at study's conclusion were rated prior to debriefing. Hierarchical
      regression identified reductions in emotional valence as a robust predictor of
      intrusions and distress. Sympathetic activation and exposure to the sadness prime
      were associated with intrusion frequency, whereas attenuated parasympathetic
      response predicted intrusion intensity. Expressive inhibition demonstrated a
      unique association with residual distress. Results suggest peritraumatic
      processes and post-exposure factors may hold more prominent relations with
      immediate trauma-related distress as compared to pre-existing survivor
      characteristics.

PMID- 28505470
TI  - Pilot test of a novel food response and attention training treatment for obesity:
      Brain imaging data suggest actions shape valuation.
AB  - Elevated brain reward and attention region response, and weaker inhibitory region
      response to high-calorie food images have been found to predict future weight
      gain. These findings suggest that an intervention that reduces reward and
      attention region response and increases inhibitory control region response to
      such foods might reduce overeating. We conducted a randomized pilot experiment
      that tested the hypothesis that a multi-faceted food response and attention
      training with personalized high- and low-calorie food images would produce
      changes in behavioral and neural responses to food images and body fat compared
      to a control training with non-food images among community-recruited
      overweight/obese adults. Compared to changes observed in controls, completing the
      intervention was associated with significant reductions in reward and attention
      region response to high-calorie food images (Mean Cohen's d = 1.54), behavioral
      evidence of learning, reductions in palatability ratings and monetary valuation
      of high-calorie foods (p = 0.009, d's = 0.92), and greater body fat loss over a 4
      week period (p = 0.009, d = 0.90), though body fat effects were not significant
      by 6-month follow-up. Results suggest that this multifaceted response and
      attention training intervention was associated with reduced reward and attention
      region responsivity to food cues, and a reduction in body fat. Because this
      implicit training treatment is both easy and inexpensive to deliver, and does not
      require top-down executive control that is necessary for negative energy balance
      obesity treatment, it may prove useful in treating obesity if future studies can
      determine how to create more enduring effects.

PMID- 28505472
TI  - Improvement of older-person-specific QOL after hearing aid fitting and its
      relation to social interaction.
AB  - PURPOSE: This study aimed to investigate whether hearing aids use is associated
      with improvement of older-person-specific QOL and whether social interactions
      modify the association. METHODS: The WHOQOL-OLD questionnaire was answered by 105
      older adults aged 60 to 90 years who were newly fitted hearing aids on the day of
      fitting and at 2 - 6 months afterward. The associations between the daily hours
      of hearing aid usage and social relations with changes in the WHOQOL-OLD total
      score after hearing aids fitting were estimated adjusting for possible
      confounders. RESULTS: Older persons with hearing loss experienced significant
      increases in WHOQOL-OLD total score after hearing aid fitting. Regular use of
      hearing aid was associated with a greater increase in the total score. The
      combined categorical variable of social relations and hearing aid usage revealed
      no separate effects of these two variables, but a combined effect; only those
      with frequent social interactions who used their hearing aid regularly had a
      significantly greater increase in WHOQOL-OLD total score. CONCLUSION: This
      study's findings indicate that hearing aid fitting may be associated with a
      subsequent improvement in older-person-specific QOL by improvements in hearing
      due to the hearing aid, and possibly enhanced communication opportunities.

PMID- 28505473
TI  - The protective study about alleviation of simvastatin on the damages of PEG-BNs
      in mice.
AB  - Boron nitride nanoparticles have been proved to cause various toxicities, damages
      or inflammations after entering into in vivo in previous reports. However, up to
      now, there are rare investigations about the alleviation of damages caused by
      nanoparticles in vivo through natural small molecule drugs. Therefore, in this
      work, PEG-BNs with high solubility was successfully synthesized, and then their
      biodistribution in mice were studied using radiolabeling technique. And the
      heart, lung, liver, spleen, kidney tissues and blood samples were done for
      histology and biochemical analysis. The results showed that PEG-BNs were mainly
      distributed in lung, liver, kidney and spleen with an obviouse decreasing
      distribution as the experimental time was increasing. Besides, significantly
      serum biochemical and tissue pathological changes induced by PEG-BNs were
      confirmed. Moreover, after simvastatin (SST) exposure to the PEG-BNs model mice,
      the damages and biochemical indexes were recovered significantly as compared to
      the single exposure group mice in serum, which indicates a good treatment effect
      on the toxicity of PEG-BNs in vivo in mice. This study provides some basic data
      and useful information for the treatment of damages caused by the nanoparticles
      in mice in the future.

PMID- 28505474
TI  - The effect of passive and active exposure to tobacco smoke on lipid profile
      parameters and the activity of certain membrane enzymes in the blood of women in
      the first trimester of pregnancy.
AB  - The effect of tobacco smoke on lipid peroxidation, the lipid profile and membrane
      bound enzymatic activity in the first trimester of pregnancy was investigated. In
      the plasma of women with active exposure to tobacco smoke, we have found
      increased lipid peroxidation and higher total concentrations of cholesterol,
      triglycerides and low-density lipoproteins in the blood, as well as a decreased
      concentration of high-density lipoproteins. A higher concentration of low-density
      lipoproteins and a lower concentration of high-density lipoproteins were also
      found in the plasma of passive smokers. In contrast, women who smoked before
      pregnancy had only a higher low-density lipoprotein concentration. In the group
      of active and passive smoking women, lower arylesterase and phosphotriesterase
      activities of paraoxonase were observed, while the lactonase activity of
      paraoxonase decreased only in the group of active smoking women. In women with
      active exposure to tobacco smoke, a higher activity level of alanine
      aminopeptidase and gamma-glutamyltransferase in the plasma was found. It is
      important to monitor the lipid profile during pregnancy, especially when exposure
      to tobacco smoke occurs.

PMID- 28505475
TI  - Colorectal cancer subtypes: Translation to routine clinical pathology.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer death in
      Europe. Although outcomes have improved, it is clear that from a genomic
      standpoint CRC is not one disease, but a heterogeneous group of malignancies that
      arise within one organ. Given that different subtypes have different outcomes,
      the ability to subtype tumours in the clinic would be highly favourable, enabling
      optimal treatment for individual patients. In 2015, a consortium proposed four
      consensus subtypes for CRC (MSI immune, canonical, metabolic, and mesenchymal)
      based on six classifications systems reported to have prognostic value. However,
      genomic assessment of tumours is not readily translated into routine pathology
      with a need for standardisation and reproducibility of assessment.
      Immunohistochemistry is widely used in routine pathology, and would present a
      more readily translatable method for subtyping CRC tumours. Therefore, the
      literature was reviewed to characterise the genomic and phenotypic features
      associated with each subtype, with the aim of enabling subtyping of CRC to be
      taken forward into routine clinical practice.

PMID- 28505476
TI  - Gender difference in the association between lower muscle mass and metabolic
      syndrome independent of insulin resistance in a middle-aged and elderly Taiwanese
      population.
AB  - BACKGROUND: Loss of muscle mass was reported to be associated with metabolic
      syndrome (MetS), but little is known about the gender difference. Thus, the aim
      of this study was to evaluate the relationship between lower muscle mass and MetS
      and determine whether there was any gender difference or not. METHODS: A total of
      394 middle-aged and elderly Taiwanese adults (138 males and 256 females) were
      enrolled and completed our health survey. They were stratified into three groups
      according to appendicular skeletal muscle mass divided by weight. Participants
      distributed into the lower tertile were defined as people having lower muscle
      mass. MetS was defined using the Adult Treatment Panel III Asian diagnostic
      criteria. Multivariate logistic regression analysis was performed to assess the
      association between muscle and MetS. RESULTS: We found an inverse association
      between MetS and muscle mass in both males and females. Participants with lower
      muscle mass had a higher risk of MetS in univariate analysis. The same results
      were observed when adjusted for age and when also adjusted for living condition
      factors. However, after additional adjustment for potential confounders and HOMA
      IR, we only found it to be statistically significant in the female group (OR in
      male=3.60; 95% CI=0.62-20.83, p=0.153; OR in female=3.03; 95% CI=1.16-7.94,
      p=0.024). CONCLUSIONS: We examined the relationship between lower muscle mass and
      metabolic syndrome in a middle-aged and elderly Taiwanese population. We found
      that lower muscle mass was associated with the risk of metabolic syndrome in the
      aged, particularly in females.

PMID- 28505477
TI  - Knowledge, behavioral practices, and experiences of outdoor fallers: Implications
      for prevention programs.
AB  - OBJECTIVE: Although the epidemiology and prevention of falls has been well
      studied, the focus has been on indoor rather than outdoor falls. Older adults'
      knowledge of outdoor risk factors and their outdoor fall prevention practices
      have not been examined. To fill this gap, and to inform the development of a
      prevention program, we sought to explore the experiences and fall prevention
      knowledge and practices of older adults who had sustained an outdoor fall.
      METHODS: A cross-sectional study using random digit telephone dialing was used to
      survey community dwelling seniors (N=120) across the five boroughs of New York
      City. We used the Outdoor Falls Questionnaire (OFQ), a valid and reliable tool as
      the survey instrument. Perceived outdoor fall risks, strategies used for
      prevention, and outdoor fall experiences were examined. SPSS version 21 was used
      for descriptive analysis of participant characteristics and to determine
      frequencies of perceived outdoor fall risks and strategies used for prevention.
      Phenomenological analysis was used with the qualitative data. Qualitative and
      quantitative data were analyzed separately and a mixed methods matrix was used to
      interpret and integrate the findings. RESULTS: Analysis revealed diverse unmet
      education and training needs including the importance of using single vision
      glasses, understanding the fall risks associated with recreational areas and
      parking lots, safe outdoor walking strategies, safe carrying of items on level
      and uneven surfaces, as well as when walking up and down stairs, and safety in
      opening/closing doors. CONCLUSIONS: Study findings are informative for outdoor
      fall prevention programs as well as practice.

PMID- 28505478
TI  - Dose assessment in environmental radiological protection: State of the art and
      perspectives.
AB  - Exposure to radiation is a potential hazard to humans and the environment. The
      Fukushima accident reminded the world of the importance of a reliable risk
      management system that incorporates the dose received from radiation exposures.
      The dose to humans from exposure to radiation can be quantified using a well
      defined system; its environmental equivalent, however, is still in a
      developmental state. Additionally, the results of several papers published over
      the last decade have been criticized because of poor dosimetry. Therefore, a
      workshop on environmental dosimetry was organized by the STAR (Strategy for
      Allied Radioecology) Network of Excellence to review the state of the art in
      environmental dosimetry and prioritize areas of methodological and guidance
      development. Herein, we report the key findings from that international workshop,
      summarise parameters that affect the dose animals and plants receive when exposed
      to radiation, and identify further research needs. Current dosimetry practices
      for determining environmental protection are based on simple screening dose
      assessments using knowledge of fundamental radiation physics, source-target
      geometry relationships, the influence of organism shape and size, and knowledge
      of how radionuclide distributions in the body and in the soil profile alter dose.
      In screening model calculations that estimate whole-body dose to biota the shapes
      of organisms are simply represented as ellipsoids, while recently developed
      complex voxel phantom models allow organ-specific dose estimates. We identified
      several research and guidance development priorities for dosimetry. For external
      exposures, the uncertainty in dose estimates due to spatially heterogeneous
      distributions of radionuclide contamination is currently being evaluated.
      Guidance is needed on the level of dosimetry that is required when screening
      benchmarks are exceeded and how to report exposure in dose-effect studies,
      including quantification of uncertainties. Further research is needed to
      establish whether and how dosimetry should account for differences in tissue
      physiology, organism life stages, seasonal variability (in ecology, physiology
      and radiation field), species life span, and the proportion of a population that
      is actually exposed. We contend that, although major advances have recently been
      made in environmental radiation protection, substantive improvements are required
      to reduce uncertainties and increase the reliability of environmental dosimetry.

PMID- 28505479
TI  - Women's self-reported experience of unplanned caesarean section: Results of a
      Swedish study.
AB  - BACKGROUND: women's experience of emergency caesarean section is often described
      as less positive compared to a vaginal birth or a planned caesarean section.
      Midwifery care for women where deviations from a normal birth process are present
      is a challenge. The aim of study was to compare self-reported birth outcomes for
      women undergoing birth through spontaneous onset of labour between those who
      actually had a vaginal birth and those who eventually had an emergency caesarean
      section. DESIGN AND SETTING: the study was part of a prospective longitudinal
      cohort study of parents' experiences, attitudes, and beliefs related to
      childbirth. METHOD AND FINDINGS: questionnaires were answered by 870 women in
      midpregnancy, two months postpartum and one year after birth. 766 women (88%) had
      a vaginal birth, and 104 (12%) had an emergency caesarean section. The most
      common indications of emergency caesarean section were dystocia, foetal distress,
      and malpresentation. Women in the emergency caesarean group were more likely to
      be primiparous (59.6%) and have a body mass index > 30 (10.7%). Childbirth fear
      was twice as common among these women, and they were more likely to have
      preferred a caesarean delivery when asked about birth preference in the middle of
      pregnancy (OR 3.7, Cl 1.8-7.5). Induction of labour (OR 2.5, Cl 1.6-4.0), the use
      of oxytocin for augmentation (OR 1.9, Cl 1.3-2.9), and the use of epidural as
      pain relief during labour (OR 5.6, Cl 3.6-8.7) were more common among women
      having an emergency caesarean section. Transport of the new-born to a neonatal
      intensive care unit was three times as common. More than a third (37%) of the
      women in the caesarean group preferred a caesarean section in case of another
      birth. Childbirth fear was more common one year after birth with 32% of these
      women describing their fear as moderate or strong (OR 3.6, CI 2.1-6.0). KEY
      CONCLUSIONS: women undergoing emergency caesarean section are more likely to
      experience fear and to have a negative birth experience. It is essential for the
      midwife to promote a sense of control, involve the woman in the procedure, and
      create security in a threatening situation. This is made possible in relationship
      characterized by mutuality, trust, on-going dialogue, shared responsibility, and
      enduring presence.

PMID- 28505480
TI  - Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable
      apoptosis mediated by reactive oxygen species.
AB  - The cytotoxic potency of a series of triphenyltin(IV) compounds of general
      composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231
      (human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3;
      isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6 are
      their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4
      (dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been
      characterized by elemental analysis and their spectroscopic properties were
      studied using IR and NMR (1H, 13C, 119Sn) techniques. The molecular structures of
      a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid
      (HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been
      determined by X-ray crystallography. Structural analyses of 2 and 5 revealed
      distorted tetrahedral geometries within C3O donor sets owing to monodentate modes
      of coordination of the respective carboxylate ligands, close intramolecular
      Sn...O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA
      MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for
      all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity
      most effectively towards MDA-MB-231 cells with a IC50 value of 1.19 and 1.44MUM,
      respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50
      value of 0.88MUM, yet the series of compounds had minimal cytotoxic effect on
      normal HEK 293 (human embryonic kidney) cell line. The underlying investigation
      suggested that the compounds exert potent antitumor effect by elevating
      intracellular reactive oxygen species generation and cause delay in cell cycle by
      inhibiting cells at G2/M phase. The results presented herein suggest further
      development of this class of triphenyltin(IV) compounds-based drugs as potential
      anti-cancer therapies should be pursued.

PMID- 28505481
TI  - Altered development, oxidative stress and DNA damage in Leptodactylus chaquensis
      (Anura: Leptodactylidae) larvae exposed to poultry litter.
AB  - Poultry litter (PL), which is usually used as organic fertilizer, is a source of
      nutrients, metals, veterinary pharmaceuticals and bacterial pathogens, which,
      through runoff, may end up in the nearest aquatic ecosystems. In this study,
      Leptodactylus chaquensis at different development stages (eggs, larval stages 28
      and 31 here referred to as stages I, II and III respectively) were exposed to PL
      test sediments as follows: 6.25% (T1), 12.5% (T2); 25% (T3); 50% (T4); 75% (T5);
      100% PL (T6) and to dechlorinated water as control. Larval survival, development
      endpoints (growth rate -GR-, development rate -DR-, abnormalities), antioxidant
      enzyme activities (Catalase -CAT- and Glutathione-S-Transferase -GST-), and
      genotoxic effect (DNA damage index by the Comet assay) were analyzed at different
      times. In stage I, no egg eclosion was observed in treatments T3-T6, and 50% of
      embryo mortality was recorded after 24h of exposure to T2. In stages II and III,
      mortality in treatments T3-T6 reached 100% between 24 and 48h. In the three
      development stages evaluated, the DR and GR were higher in controls than in PL
      treatments (T1, T2), except for those T1-treated larvae of stage II. Larvae of
      stage I showed five types of morphological abnormalities, being diamond body
      shape and lateral displacement of the intestine the most prevalent in T1, whereas
      larvae of stages II and III presented lower prevalence of abnormalities. In stage
      I, CAT activity was similar to that of control (p>0.05), whereas it was higher in
      T1- and T2- treated larvae of stages II and III than controls (p<0.05). In stages
      I and III, GST activity was similar to that of controls (p>0.05), whereas it was
      inhibited in T1-treated larvae of stage II (p<0.05). T1- and T2-treated larvae of
      stages II and III caused higher DNA damage respect to controls (p<0.05), varying
      from medium to severe damage (comet types II, III and IV). These results showed
      that PL treatments altered development and growth and induced oxidative stress
      and DNA damage, resulting ecotoxic for L. chaquensis larvae.

PMID- 28505482
TI  - Conservation efforts of captive golden takin (Budorcas taxicolor bedfordi) are
      potentially compromised by the elevated chemical elements exposure.
AB  - Chemical elements exposure of endangered golden takins (Budorcas taxicolor
      bedfordi) living in the Qinling Mountains and in a captive breeding center was
      assessed by analyzing fecal samples. Concentrations of As, Co, Cr, Cu, Ni and Se
      were significantly higher in the feces of captive golden takins than the wild.
      There was no significant difference in the fecal concentrations of Cd, Mn, Hg, Pb
      or Zn for wild and captive animals. The element concentration of fecal samples
      collected from captive animals varied seasonally, with concentrations being
      lowest in spring and highest in winter and/or autumn. The food provided to
      captive animals varied both in the composition and the concentration of element
      present. Consumptions of feedstuff and additional foods such as D. sanguinalis
      and A. mangostanus for the captive golden takins were identified as the possible
      sources of chemical element exposure. The estimations of dietary intake of most
      elements by captive takins were below the oral reference dose, except for As and
      Pb, indicating that As and Pb were the key components which contributed to the
      potential non-carcinogenic risk for captive golden takins. In conclusion, captive
      golden takins were exposed to higher concentrations of chemical elements compared
      with the wild, which were likely due to their dietary difference. Conservation
      efforts of captive golden takin are potentially compromised by the elevated
      chemical element exposure and effort should focus on providing uncontaminated
      food for captive animals.

PMID- 28505483
TI  - The effects of ingested aqueous aluminum on floral fidelity and foraging strategy
      in honey bees (Apis mellifera).
AB  - Pollinator decline is of international concern because of the economic services
      these organisms provide. Commonly cited sources of decline are toxicants, habitat
      fragmentation, and parasites. Toxicant exposure can occur through uptake and
      distribution from plant tissues and resources such as pollen and nectar. Metals
      such as aluminum can be distributed to pollinators and other herbivores through
      this route especially in acidified or mined areas. A free-flying artificial
      flower patch apparatus was used to understand how two concentrations of aluminum
      (2mg/L and 20mg/L) may affect the learning, orientation, and foraging behaviors
      of honey bees (Apis mellifera) in Turkey. The results show that a single dose of
      aluminum immediately affects the floral decision making of honey bees potentially
      by altering sucrose perception, increasing activity level, or reducing the
      likelihood of foraging on safer or uncontaminated resource patches. We conclude
      that aluminum exposure may be detrimental to foraging behaviors and potentially
      to other ecologically relevant behaviors.

PMID- 28505484
TI  - Arsenic speciation in the phloem exudates of rice and its role in arsenic
      accumulation in rice grains.
AB  - Arsenic (As) speciation in the phloem sap of rice plants and its role in As
      accumulation in rice grains remain largely uncharacterized. In the present study,
      we tested As chemical species in the phloem exudates of rice treated with
      arsenate [As(V)], arsenite [As(III)], monomethylarsonic acid [MMA(V)], or
      dimethylarsinic acid [DMA(V)]. As(V) was the main species (58%) in the phloem
      exudates of As(V)-exposed rice, whereas As(III) predominated (69%) in As(III)
      exposed rice. A large proportion of As(V) (41-45%) was observed in the phloem
      exudates when rice was treated with methylated As species. High concentrations of
      phytochelatins were detected in the phloem exudates when the As(V) treatment
      level was increased. The role of phloem transport was analyzed by applying a +/
      stem-girdling treatment to the rice plants, limiting phloem transport to the
      grain in rice pulsed with As(III), As(V), MMA(V), or DMA(V). The findings of the
      present study indicate that organic As is more mobile than inorganic As during
      phloem transport. Phloem transport accounted for 54% of As(III), 56% of As(V),
      100% of MMA(V), and 89% of DMA(V) transport to the grain. The total As
      concentration and As(III) percentage in rice phloem and grain were significantly
      affected by increasing the phosphate concentration in the medium.

PMID- 28505485
TI  - Interventions affecting mortality in critically ill and perioperative patients: A
      systematic review of contemporary trials.
AB  - PURPOSE: Confounders in randomized controlled trials (RCTs) reporting significant
      effects on mortality in critically ill patients using non-surgical techniques
      have not been systematically explored. We aimed to identify factors unrelated to
      the reported intervention that might have affected the findings and robustness of
      such trials. METHODS: We searched Pubmed/MEDLINE for all RCTs on any non-surgical
      interventions reporting an effect on unadjusted mortality in critically ill
      patients between 1/1/2000 and 1/12/2015. We assessed: the number needed to
      treat/harm (NNT or NNH), sample size, trial design (blinded/unblinded, single or
      multinational, single or multicenter (sRCT or mRCT)), intention to treat (ITT)
      analysis, and countries of origin. RESULTS: Almost half of RCTs were sRCTs.
      Median sample size was small, and 1/3 were not analyzed according to ITT
      principle. Lack of ITT analysis was associated with greater effect size
      (p=0.0028). Harm was more likely in mRCTs (p=0.002) and/or in blinded RCTs
      (p=0.003). Blinded RCTs had double sample size (p=0.007) and an increased NNT/NNH
      (p=0.002). Finally, mRCTs had higher NNT (p=0.005) and NNH (p=0.02), and harm was
      only detected in studies from Western countries (p=0.007). CONCLUSIONS: These
      observations imply that major systematic biases exist and affect trial findings
      irrespective of the intervention being studied.

PMID- 28505486
TI  - Respiratory support techniques to avoid desaturation in critically ill patients
      requiring endotracheal intubation: A systematic review and meta-analysis.
AB  - PURPOSE: To evaluate which respiratory support method for critically ill patients
      undergoing endotracheal intubation (ETI) is associated with less desaturation.
      METHODS: We searched PubMed, Cochrane Library, Scopus and CINAHL databases. We
      included randomized (RCT) and non-randomized (non-RCT) studies investigating any
      method of respiratory support before/during ETI compared to a reference control.
      RESULTS: Apneic oxygenation (ApOx) was the most commonly investigated respiratory
      support technique for critically ill patients undergoing intubation (4 RCTs, 358
      patients). Three of these studies investigated high-flow nasal cannula (HFNC) for
      ApOx while standard nasal cannula was used in one. Globally, ApOx was associated
      with higher minimum SpO2 value compared to those receiving ETI without ApOx (mean
      difference 2.31%, 95% CI 0.42 to 4.20, p=0.02, I2=0%) but there were not
      significant differences between groups in severe hypoxemia and intubation related
      - complications. Concerning other techniques, noninvasive ventilation (NIV) was
      compared to bag-valve mask in only one RCT and it reduced the degree of
      desaturation. CONCLUSIONS: ApOx was significantly associated with higher minimum
      SpO2 registered during the intubation procedure. Further studies are needed to
      increase the number of included patients and demonstrate the benefit of ApOx and
      of other respiratory support methods (e.g. NIV, HFNC).

PMID- 28505487
TI  - Heroin refusal self-efficacy and preference for medication-assisted treatment
      after inpatient detoxification.
AB  - OBJECTIVE: An individual's self-efficacy to refuse using heroin in high-risk
      situations is believed to minimize the likelihood for relapse. However, among
      individuals completing inpatient heroin detoxification, perceived refusal self
      efficacy may also reduce one's perceived need for medication-assisted treatment
      (MAT), an effective and recommended treatment for opioid use disorder. In the
      current study, we examined the relationship between heroin refusal self-efficacy
      and preference for MAT following inpatient detoxification. METHOD: Participants
      (N=397) were interviewed at the start of brief inpatient opioid detoxification.
      Multiple logistic regression was used to estimate the adjusted association of
      background characteristics, depressed mood, and perceived heroin refusal self
      efficacy with preference for MAT. RESULTS: Controlling for other covariates,
      depressed mood and lower perceived refusal self-efficacy were associated with a
      significantly greater likelihood of expressing preference for MAT (versus no
      MAT). CONCLUSIONS: Perceived ability to refuse heroin after leaving detox is
      inversely associated with a heroin user's desire for MAT. An effective continuum
      of care model may benefit from greater attention to patient's perceived refusal
      self-efficacy during detoxification which may impact preference for MAT and long
      term recovery.

PMID- 28505488
TI  - Predictors of buprenorphine treatment success of opioid dependence in two
      Baltimore City grassroots recovery programs.
AB  - INTRODUCTION: Despite evidence for the efficacy of buprenorphine treatment in
      primary care, few studies have identified factors associated with treatment
      success, nor have such factors been evaluated in community settings. Identifying
      correlates of treatment success can facilitate the development of treatment
      models tailored for distinct populations, including low-income communities of
      color. The current study examined client-level socio-demographic factors
      associated with treatment success in community-based buprenorphine programs
      serving vulnerable populations. METHODS: Data were abstracted from client records
      for participants (N=445) who met DSM-IV criteria for opioid dependence and sought
      treatment at one of Behavioral Health Leadership Institute's two community-based
      recovery programs in Baltimore City from 2010 to 2015. Logistic regression
      estimated the odds ratios of treatment success (defined as retention in treatment
      for >=90days) by sociodemographic predictors including age, race, gender,
      housing, legal issues and incarceration. RESULTS: The odds of being retained in
      treatment >=90days increased with age (5% increase with each year of age;
      p<0.001), adjusting for other sociodemographic factors. Clients who reported
      unstable housing had a 41% decreased odds of remaining in treatment for 90 or
      more days compared to clients who lived independently at intake. Treatment
      success did not significantly differ by several other client-level
      characteristics including gender, race, employment, legal issues and
      incarceration. CONCLUSIONS: In vulnerable populations, the age factor appears
      sufficiently significant to justify creating models formulated for younger
      populations. The data also support attention to housing needs for people in
      treatment. Findings from this paper can inform future research and program
      development.

PMID- 28505489
TI  - Anxiety sensitivity as a predictor of outcome in the treatment of obsessive
      compulsive disorder.
AB  - BACKGROUND AND OBJECTIVES: To address the fact that not all individuals who
      receive cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder
      (OCD) exhibit complete symptom reduction, research has examined factors that
      predict outcome; however, no studies have examined anxiety sensitivity (AS) as a
      predictor of outcome of CBT for OCD. AS refers to the fear of anxious arousal
      that results from mistaken beliefs about the dangerousness of anxiety-related
      body sensations. It is important to understand whether AS influences OCD
      treatment outcome, considering that (a) some obsessions directly relate to AS,
      and (b) OCD patients with high AS may be reluctant to engage in anxiety-provoking
      components of CBT for OCD. METHODS: Patients (N = 187) with a primary diagnosis
      of OCD who received residential CBT for OCD participated in this study, which
      involved completing a self-report battery at pre- and post-treatment. RESULTS:
      Results supported study hypotheses, in that (a) baseline AS positively correlated
      with baseline OCD severity, and (b) greater baseline AS prospectively predicted
      higher posttreatment OCD symptom severity even after controlling for pretreatment
      OCD and depression severity. LIMITATIONS: The study was limited by its use of an
      older measure of AS, reliance on self-report measures, and nonstandardized
      treatment across participants. CONCLUSIONS: Findings highlight the importance of
      AS in the nature and treatment of OCD. Clinical implications and future
      directions are discussed.

PMID- 28505491
TI  - Development of suitable method for large-scale urinary glucocorticoid analysis by
      liquid chromatography-mass spectrometry.
AB  - Levels of urinary glucocorticoids and their concentration ratios have been
      analyzed as potential markers for various pathological statuses. Large-scale
      studies may possibly accelerate the investigations; however, a suitable method
      needs to be established. Analytical conditions for measurement of urinary
      glucocorticoids with LCMS were examined. Electrospray ionization in the positive
      ion mode was applied for detection of cortisol (precursor>product ion:
      363.3>121.0), cortisol-d4 (internal standard, IS, 367.4>121.1), and cortisone
      (361.2>163.2). To maximize ionization, acetic acid-ammonium acetate buffer (18mM)
      at pH 5.3 was employed as eluent A. A C18 column (100mm*2.1mm, 2.7MUm) at 50
      degrees C was used for the 9.5min binary gradient separation starting with 60%
      eluent A with methanol being eluent B. Linear correlations were observed between
      the concentrations and the peak areas in the concentration range of 1-300ng/mL
      with correlation coefficients (r) of 0.998 and 0.997 for cortisol and cortisone,
      respectively, without IS adjustment, and 0.999 with IS adjustment for both
      cortisol and cortisone. Solid-phase extraction (SPE) using a 2mL centrifuge
      column was performed for the urine samples, with the original and final volumes
      being 100MUL. The SPE of 12 urine specimens could be performed within 30min. The
      effect of the sample matrix on the quantification of endogenous compounds present
      in the urine extract was limited (coefficient of variation (CV) of IS-adjusted
      matrix factor: 4.4-8.1%; urine extracts of 8 individuals); however, substantial
      peak reduction of cortisol was observed at low concentrations. Exogenous
      contaminants originating from the SPE centrifuge column seemed to be a main cause
      for this phenomenon because the pure-water extract showed similar peak reduction.
      A recovery of ~50% was obtained for both cortisol and cortisone. Adjustment with
      the IS improved the apparent recovery, with ~100% being obtained for both
      cortisol and cortisone. The recovery rate decreased when the urine samples were
      concentrated in the SPE step; the reduction was greater for cortisol than for
      cortisone. The lower limit of quantification (LLOQ) was set at 2.5ng/mL when the
      injection volume was 10MUL, based on the reproducibility of the standards which
      were measured (CV of 12 repetitions: 10.1% for 0.5ng/mL cortisol and 19.6% for
      1ng/mL cortisone), the matrix effect (-55% at 2ng/mL concentrations of cortisol),
      and the recovery rate (~50%). Furthermore an alternative approach for preparation
      of the cortisol standards was required for low concentration range (2.5-20ng/mL)
      because of the effect of the matrix. Degradation of original urine specimens at
      room temperature was minimal during the first 24h. The extracted urine samples
      degraded over time; however, their concentrations were corrected with the IS,
      allowing for analysis up to 5days after extraction. In conclusion, an analytical
      method for urinary glucocorticoids was established, which is fast, sensitive, and
      well suited for practical application to large-scale study.

PMID- 28505490
TI  - Heat induced temperature dysregulation and seizures in Dravet Syndrome/GEFS+
      Gabrg2+/Q390X mice.
AB  - It has been established that febrile seizures and its extended syndromes like
      generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome
      have been associated with mutations especially in SCN1A and GABRG2 genes. In
      patients, the onset of FS is likely due to the combined effect of temperature and
      inflammation in genetically vulnerable individuals because fever is often
      associated with infection. Much effort has been spent to understand the
      mechanisms underlying fever induction of seizures. In addition to the role of
      cytokines in FS, previous studies in Scn1a+/- knockout mice, a model of Dravet
      syndrome, indicated that temperature elevation alone could result in seizure
      generation, and the effect of elevated temperature inducing seizures was age
      dependent. Here, we report the thermal effect in a different mouse model of
      Dravet syndrome, the Gabrg2+/Q390X knockin mouse. We demonstrated age-dependent
      dysregulated temperature control and that temperature elevation produced
      myoclonic jerks, generalized tonic clonic seizures (GTCSs) and heightened anxiety
      like symptoms in Gabrg2+/Q390X mice. The study indicated that regardless of other
      inflammatory factors, brief heat alone increased brain excitability and induced
      multiple types of seizures in Gabrg2+/Q390X mice, suggesting that mutations like
      GABRG2(Q390X) may alter brain thermal regulation and precipitate seizures during
      temperature elevations.

PMID- 28505492
TI  - Comprehensive evaluation of SCFA production in the intestinal bacteria regulated
      by berberine using gas-chromatography combined with polymerase chain reaction.
AB  - Short-chain fatty acids (SCFAs) of intestine microbial have caught accumulating
      attention for their beneficial effects on human health. Botanic compounds with
      low bioavailability such as berberine (BBR) and resveratrol might interact with
      intestinal microbial ecosystem and promote gut bacteria to produce SCFA, which
      contribute to their biological effects. In the present study, a comprehensive
      assay system was built to detect SCFAs production in intestinal bacteria, in
      which stringent anaerobic culture was applied for in vitro bacterial
      fermentation, followed by direct-injection GC detection (chemical detection) in
      combination with real time polymerase chain reaction (RT-PCR, biological
      detection). BBR was used as positive reference. The direct injection GC method
      was calibrated and successfully applied to analyze the concentration of SCFAs in
      gut microbiota and BBR was proved to be effective in the dose- and time-dependent
      up-regulation of SCFAs production. As compared to the saline group, the
      concentration of acetic acid, propionate acid and butyric acid (the main SCFAs in
      gut microbiota) were increased by 17.7%, 11.1% and 30.5%, respectively, after
      incubating intestinal bacteria with 20MUg/mL BBR for 24h. The increase reached to
      34.9%, 22.4% and 51.6%, respectively when the BBR was 50MUg/mL. Additionally,
      consensus-degenerate hybrid oligonucleotide primers (CODEHOPs) were designed for
      the detection of acetate kinase (ACK), Methylmalonyl-CoA decarboxylase (MMD) and
      butyryl-CoA: acetate-CoA transferase (BUT), as they are the key enzymes in the
      synthetic pathway for acetic acid, propionate acid and butyric acid,
      respectively. After 24hr's incubation, BBR was shown to promote the gene
      expression of ACK, MMD and BUT significantly (86.5%, 27.2% and 60.4%,
      respectively, with 20MUg/mL BBR; 130.2%, 84.2% and 98.4%, respectively, with
      50MUg/mL BBR), showing a solid biological support for the chemical detection.
      This comprehensive assay system might be useful in identifying SCFAs promoting
      agents with information on their mechanism.

PMID- 28505493
TI  - Development of an analysis method for determination of sulfonamides and their
      five acetylated metabolites in baby foods by ultra-high performance liquid
      chromatography coupled to high-resolution mass spectrometry (Orbitrap-MS).
AB  - A high sensitive and reliable multiresidue method was developed and validated for
      determination of twelve sulfonamides and five acetylated metabolites in baby
      foods by using UHPLC-Orbitrap-MS. The sample preparation included two extraction
      methods as QuEChERS and ASE. The original QuEChERS method was performed, whereas
      ASE method was optimized to achieve the best recovery for all analytes. UHPLC
      Orbitrap-MS parameters were optimized to obtain good retention and separation in
      LC and high sensitivity and selectivity in MS. The performance of the method was
      evaluated according to the European Commision Decision 2002/657/EC. Matrix
      matched calibration curves showed good r2 (>=0.999) and LOQ was ranged from 0.10
      to 0.55MUg/kg. ASE was significantly more effective for extraction of the
      analytes (recovery ranged from 75.5 to 96.6% with RSD<=10.1%) than QuEChERS
      (recovery ranged from 60.9 to 85.9% with RSD<=19.1%). This method was applied to
      the analysis of 47 different baby foods and no positive samples were found.

PMID- 28505494
TI  - Melatonin protects mice against stress-induced inflammation through enhancement
      of M2 macrophage polarization.
AB  - Stress is known to cause neuropsychiatric diseases, and it has a detrimental
      impact on the function of the immune system. Melatonin (MLT), a pineal gland
      hormone, exhibits potent anti-inflammatory properties and it plays a fundamental
      role in neuroimmunomodulation. In the present study, we investigated the
      molecular mechanisms of MLT in stress-induced inflammation, focusing on
      macrophage polarization. MLT (50 and 100mg/kg) or a vehicle control (5% ethanol
      in saline) was intraperitoneally administered to mice once a day for 5days. After
      the last treatment, mice were subjected to restraint stress (RS) for 2h. MLT
      markedly decreased serum levels of corticosterone after RS. RS significantly
      increased serum interleukin (IL)-1beta and IL-6 levels, and it decreased serum IL
      10 levels. MLT administration attenuated these changes. After RS, MLT markedly
      decreased lipid peroxidation and increased hepatic glutathione content. In
      purified Kupffer cells (KCs) and peritoneal macrophages from mice exposed to RS,
      the expression levels of M1 marker genes (NOS2a and CD40) increased, while the
      expression levels of an M2 marker gene (Arg1) decreased. MLT attenuated this
      increase in expression of M1 marker genes and decrease in the expression levels
      of the M2 marker gene. Furthermore, in KCs and peritoneal macrophages exposed to
      RS, MLT decreased the number of F4/80+CD86+ cells and increased the number of
      F4/80+MRC1+ cells. In splenocytes exposed to RS, MLT inhibited the increase in
      mRNA expression of NOS2a. MLT downregulated expression of phosphorylated signal
      transducer and activator of transcription (STAT) 1 and upregulated STAT3 protein
      expression. Our findings suggest that MLT reduces stress-induced inflammatory
      responses by inducing an M1 to M2 phenotype switch in macrophages via activation
      of STAT3 signaling.

PMID- 28505495
TI  - Generalized Boussinesq-Scriven surface fluid model with curvature dissipation for
      liquid surfaces and membranes.
AB  - Curvature dissipation is relevant in synthetic and biological processes, from
      fluctuations in semi-flexible polymer solutions, to buckling of liquid columns,
      tomembrane cell wall functioning. We present a micromechanical model of curvature
      dissipation relevant to fluid membranes and liquid surfaces based on a parallel
      surface parameterization and a stress constitutive equation appropriate for
      anisotropic fluids and fluid membranes.The derived model, aimed at high curvature
      and high rate of change of curvature in liquid surfaces and membranes, introduces
      additional viscous modes not included in the widely used 2D Boussinesq-Scriven
      rheological constitutive equation for surface fluids.The kinematic tensors that
      emerge from theparallel surface parameterization are the interfacial rate of
      deformation and the surface co-rotational Zaremba-Jaumann derivative of the
      curvature, which are used to classify all possibledissipative planar and non
      planar modes. The curvature dissipation function that accounts for bending,
      torsion and twist rates is derived and analyzed under several constraints,
      including the important inextensional bending mode.A representative application
      of the curvature dissipation model to the periodic oscillation in nano-wrinkled
      outer hair cells show how and why curvature dissipation decreases with frequency,
      and why the 100kHz frequency range is selected. These results contribute to
      characterize curvature dissipation in membranes and liquid surfaces.

PMID- 28505496
TI  - Inactivation of Gram (-) bacteria Salmonella enterica by chlorophyllin-based
      photosensitization: Mechanism of action and new strategies to enhance the
      inactivation efficiency.
AB  - This study is focused on the enhancement of susceptibility of Gram (-) bacteria
      S. enterica to chlorophyllin-based (Chl) photosensitization combining it with
      other antimicrobial tools. In order to find best combinations, the mechanism by
      which Chl-based photosensitization inactivates bacteria must be identified. Data
      confirmed that photosensitization (Chl 1.5*10-5M, for 1-120min, 405nm, 0
      46.1J/cm2) reduced S. enterica population, just by 2.05 log (CFU/ml).
      Fluorimetric measurements indicated that just minor part of Chl was bound to
      Salmonella in suspension. Addition of sodium azide (NaN3) (10mM) protected
      bacteria from killing, what means that 1O2 took place in photochemical reactions.
      Gene expression data confirmed that Chl-based photosensitization induced
      oxidative stress in bacteria cells, since mostly genes responsible for
      detoxification of ROS (OxyR, AhpC, GrxA) have been expressed in Salmonella.
      Moreover, the expression of genes, responsible for the inhibition of oxidative
      respiration (AtpC), cell division and down-regulation of metabolism (SulA) have
      been detected. In addition, Chl-based photosensitization induced significant
      release of intracellular components (absorbing at lambda260 nm and lambda280 nm)
      in bacteria that indicated increased membrane permeability. Thus, the combination
      of two antimicrobials (Chl-based photosensitization and chitosan (CHS)) with the
      same target (cellular membrane) in the presence of light drastically reduced
      viable Salmonella population (by 7.28 log). Combined treatment of
      photosensitization and high power pulsed UV light (HPPL) was also very effective,
      since reduced viable Salmonella by 7.5 log. Bacterial regrowth experiments
      clearly indicated that after both combined treatments Salmonella lost its ability
      to proliferate, and SEM images confirmed that after both treatments no viable
      bacteria have been found at all.

PMID- 28505497
TI  - Binding of ciprofloxacin to bovine serum albumin: Photophysical and thermodynamic
      aspects.
AB  - The present work reveals the study of interaction of a promising chemotherapeutic
      drug ciprofloxacin (CFX) with a model transport protein bovine serum albumin
      (BSA). The occurrence of the drug-protein interaction is found to result in
      significant modulations of the fluorescence excitation and emission spectroscopic
      properties of CFX following interaction with BSA. However, the major focus of the
      study underlies a critical insight into the quantitation of the drug-protein
      interaction phenomenon. To this end, we have exploited the isothermal titration
      calorimetric (ITC) technique to quantify the affinity constant (Ka) and
      stoichiometry (n) of the CFX-BSA interaction with simultaneous revelation of the
      accompanying thermodynamics of the interaction process. In this context, our
      discussion also sheds light on the lacuna surrounding various experimental
      methodologies for evaluation of drug-protein binding parameters. Our endeavor
      also extends to elucidation of the kinetic parameters and energy of activation
      (Ea) of the CFX-BSA interaction. The present study also delineates the modulation
      of the dynamical aspects of CFX following interaction with BSA. The rotational
      relaxation dynamics of the protein-bound drug reveals the not-so-common "dip-rise
      dip" anisotropy decay. Furthermore, the effect of drug binding on the native
      protein conformation has been evaluated from circular dichroism (CD) spectroscopy
      which reveals partial rupture of the protein secondary structure.

PMID- 28505498
TI  - Ameliorative effects of rutin on hepatic encephalopathy-induced by thioacetamide
      or gamma irradiation.
AB  - Hepatic encephalopathy (HE) is a syndrome resulting from acute or chronic liver
      failure. This study was designed to evaluate the effect of rutin on thioacetamide
      (TAA) or gamma-radiation-induced HE model. Animals were received with TAA
      (200mg/kg, i.p.) twice weekly for four weeks or exposed to 6Gy of gamma-radiation
      to induce HE then groups orally treated with rutin (50mg/kg b.wt.) for four
      weeks. At the end of experiment, blood, liver and brain samples were collected to
      assess biochemical and biophysical markers as well histopathological
      investigations. TAA or gamma-radiation exposed rats experienced increases in
      serum activities of ALT, AST, ALP and ammonia level. Also an alteration in
      relative permeability and conductivity of erythrocytes was observed. Furthermore,
      cytokines levels and AChE activity were induced whereas the activities of HO-1
      and neurotransmitters contents were depleted. TAA or gamma-radiation caused
      distortion of hepatic and brain architecture as shown by histopathological
      examination. Treatment with rutin resulted in improvement in liver function by
      the decline in serum AST and ALT activities and reduction in serum ammonia level.
      In addition, the administration of rutin significantly modulated the alteration
      in cytokines levels and neurotransmitters content. Histopathological examinations
      of liver and brain tissues showed that administration of rutin has attenuate TAA
      or radiation-induced damage and improve tissue architecture. Consequently, rutin
      has been a powerful hepatoprotective effect to combat hepatic encephalopathy
      associated hyperammonemia and its consequential damage in liver and brain.

PMID- 28505499
TI  - Clinical predictors of acute response to transcranial direct current stimulation
      (tDCS) in major depression.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising
      neuromodulation intervention for poor-responding or refractory depressed
      patients. However, little is known about predictors of response to this therapy.
      The present study aimed to analyze clinical predictors of response to tDCS in
      depressed patients. METHODS: Clinical data from 3 independent tDCS trials on 171
      depressed patients (including unipolar and bipolar depression), were pooled and
      analyzed to assess predictors of response. Depression severity and the underlying
      clinical dimensions were measured using the Hamilton Depression Rating Scale
      (HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis
      (bipolar/unipolar depression) were also investigated as predictors of response.
      Linear mixed models were fitted in order to ascertain which HDRS factors were
      associated with response to tDCS. RESULTS: Age, gender and diagnosis did not show
      any association with response to treatment. The reduction in HDRS scores after
      tDCS was strongly associated with the baseline values of "Cognitive Disturbances"
      and "Retardation" factors, whilst the "Anxiety/Somatization" factor showed a mild
      association with the response. LIMITATIONS: Open-label design, the lack of
      control group, and minor differences in stimulation protocols. CONCLUSIONS: No
      differences in response to tDCS were found between unipolar and bipolar patients,
      suggesting that tDCS is effective for both conditions. "Cognitive disturbance",
      "Retardation", and "Anxiety/Somatization", were identified as potential clinical
      predictors of response to tDCS. These findings point to the pre-selection of the
      potential responders to tDCS, therefore optimizing the clinical use of this
      technique and the overall cost-effectiveness of the psychiatric intervention for
      depressed patients.

PMID- 28505500
TI  - Increase in the prescription rate of antidepressants after the Sewol Ferry
      disaster in Ansan, South Korea.
AB  - BACKGROUND: Previous pharmaco-epidemiological studies have reported increases in
      the prescription of psychotropic medications after a disaster, reflecting post
      disaster changes in psychiatric conditions and mental health service utilization.
      We investigated changes in the prescription of psychotropic medications in the
      Danwon district of Ansan city (Ansan Danwon) compared to a control community
      before and after the Sewol Ferry disaster on April 16, 2014. METHODS: Data was
      collected from the Korean Health Insurance Review and Assessment Service
      database. We analyzed the prescription rates of psychotropic medications
      including antidepressants, anxiolytics, and sedatives/hypnotics, and investigated
      whether the time-series pattern of monthly prescriptions per 100,000 people was
      different in Ansan Danwon compared to that in Cheonan city after the Sewol Ferry
      disaster through difference-in-differences regression analysis. RESULTS: Ansan
      Danwon showed a significantly greater increase (5.6%) in the prescription rate of
      antidepressants compared to Cheonan city following the Sewol Ferry disaster.
      There were no significant differences in changes in the prescription rates of
      anxiolytics or sedatives/hypnotics. In the secondary analysis, a significantly
      greater increase in the prescription rate of antipsychotics was observed in Ansan
      Danwon compared to a control community after the disaster. LIMITATIONS: We could
      not exclude the possibility that other events influenced changes in the
      prescription rates of psychotropic medications during the study period.
      CONCLUSIONS: Pharmaco-epidemiological studies on psychotropic medication
      prescription after a disaster provide important information about population
      level mental health. Our results suggest that the Sewol Ferry disaster exerted a
      harmful effect on the mental health status of the affected community.

PMID- 28505501
TI  - Cognitive-affective depression and somatic symptoms clusters are differentially
      associated with maternal parenting and coparenting.
AB  - BACKGROUND: Both depressive and somatic symptoms are significant predictors of
      parenting and coparenting problems. However, despite clear evidence of their co
      occurrence, no study to date has examined the association between depressive
      somatic symptoms clusters and parenting and coparenting. The current research
      sought to identify and cross-validate clusters of cognitive-affective depressive
      symptoms and nonspecific somatic symptoms, as well as to test whether clusters
      would differ on parenting and coparenting problems across three independent
      samples of mothers. METHOD: Participants in Studies 1 and 3 consisted of 409 and
      652 community mothers, respectively. Participants in Study 2 consisted of 162
      mothers exposed to intimate partner violence. All participants prospectively
      completed self-report measures of depressive and nonspecific somatic symptoms and
      parenting (Studies 1 and 2) or coparenting (Study 3). RESULTS: Across studies,
      three depression-somatic symptoms clusters were identified: no symptoms, high
      depression and low nonspecific somatic symptoms, and high depression and
      nonspecific somatic symptoms. The high depression-somatic symptoms cluster was
      associated with the highest levels of child physical maltreatment risk (Study 1)
      and overt-conflict coparenting (Study 3). No differences in perceived maternal
      competence (Study 2) and cooperative and undermining coparenting (Study 3) were
      found between the high depression and low somatic symptoms cluster and the high
      depression-somatic symptoms cluster. CONCLUSIONS: The results provide novel
      evidence for the strong associations between clusters of depression and
      nonspecific somatic symptoms and specific parenting and coparenting problems.
      Cluster stability across three independent samples suggest that they may be
      generalizable. The results inform preventive approaches and evidence-based
      psychotherapeutic treatments.

PMID- 28505502
TI  - Sleep in the northern fur seal.
AB  - The pattern of sleep in the fur seal, a semiaquatic pinniped, has several
      striking behavioral and physiological adaptations that allow this species to
      inhabit both the land and water environment. These features include
      unihemispheric slow wave sleep (USWS, also being unihemispheric waking), the
      ability to maintain movement for stabilization of the sleep posture and to
      briefly open one eye while having a sleep electroencephalogram (EEG) in one
      hemisphere. In vivo microdialysis studies suggest that acetylcholine release is
      required for cortical activation during USWS, and that monoamines are not
      required for USWS. The need to breathe, to maintain efficient thermoregulation,
      and to avoid predation have shaped the sleep patterns in semiaquatic fur seals as
      in fully aquatic cetaceans.

PMID- 28505503
TI  - Intracranial neurenteric cyst mimicking an ependymoma: imaging features,
      pathologic correlation and review of literature.
AB  - We present a case of a 57-year-old female with four-months of diplopia and
      vertigo. MRI revealed a mixed cystic and solid partially enhancing lesion of the
      4th ventricle, foramen of Luschka and cerebellopontine angle. Preoperative
      differential diagnosis favored ependymoma. Biopsy revealed a neurenteric cyst, a
      benign developmental lesion that rarely occurs intracranially. This case
      highlights several atypical manifestations of intracranial neurenteric cyst, with
      regions of histologically benign solid enhancement, multicompartmental extra
      axial location mimicking an ependymoma, and rapid recurrence without evidence of
      underlying malignancy.

PMID- 28505505
TI  - Measuring listening-related effort and fatigue in school-aged children using
      pupillometry.
AB  - Stress and fatigue from effortful listening may compromise well-being, learning,
      and academic achievement in school-aged children. The aim of this study was to
      investigate the effect of a signal-to-noise ratio (SNR) typical of those in
      school classrooms on listening effort (behavioral and pupillometric) and
      listening-related fatigue (self-report and pupillometric) in a group of school
      aged children. A sample of 41 normal-hearing children aged 8-11years performed a
      narrative speech-picture verification task in a condition with recommended levels
      of background noise ("ideal": +15dB SNR) and a condition with typical classroom
      background noise levels ("typical": -2dB SNR). Participants showed increased task
      evoked pupil dilation in the typical listening condition compared with the ideal
      listening condition, consistent with an increase in listening effort. No
      differences were found between listening conditions in terms of performance
      accuracy and response time on the behavioral task. Similarly, no differences were
      found between listening conditions in self-report and pupillometric markers of
      listening-related fatigue. This is the first study to (a) examine listening
      related fatigue in children using pupillometry and (b) demonstrate physiological
      evidence consistent with increased listening effort while listening to spoken
      narratives despite ceiling-level task performance accuracy. Understanding the
      physiological mechanisms that underpin listening-related effort and fatigue could
      inform intervention strategies and ultimately mitigate listening difficulties in
      children.

PMID- 28505506
TI  - A methodology for efficiency optimization of betavoltaic cell design using an
      isotropic planar source having an energy dependent beta particle distribution.
AB  - Nuclear batteries based on silicon carbide betavoltaic cells have been studied
      extensively in the literature. This paper describes an analysis of design
      parameters, which can be applied to a variety of materials, but is specific to
      silicon carbide. In order to optimize the interface between a beta source and
      silicon carbide p-n junction, it is important to account for the specific
      isotope, angular distribution of the beta particles from the source, the energy
      distribution of the source as well as the geometrical aspects of the interface
      between the source and the transducer. In this work, both the angular
      distribution and energy distribution of the beta particles are modeled using a
      thin planar beta source (e.g., H-3, Ni-63, S-35, Pm-147, Sr-90, and Y-90) with
      GEANT4. Previous studies of betavoltaics with various source isotopes have shown
      that Monte Carlo based codes such as MCNPX, GEANT4 and Penelope generate similar
      results. GEANT4 is chosen because it has important strengths for the treatment of
      electron energies below one keV and it is widely available. The model
      demonstrates the effects of angular distribution, the maximum energy of the beta
      particle and energy distribution of the beta source on the betavoltaic and it is
      useful in determining the spatial profile of the power deposition in the cell.

PMID- 28505504
TI  - Standardization of the apparent diffusion coefficient value of bladder cancer
      across different centers: Applicability in predicting aggressive pathologic
      phenotypes.
AB  - PURPOSE: We investigated whether the standardized apparent diffusion coefficient
      (ADC) value reflects bladder cancer characteristics across different centers.
      METHODS: Ninety-eight bladder cancer patients underwent MRI at two institutions.
      Standardized tumor ADC (sT-ADC) was calculated by dividing absolute tumor ADC (aT
      ADC) by that of gluteus maximus. We compared ADCs between MRI protocols according
      to grade and T-stage. RESULTS: The differences in aT-ADC between MRI protocols
      were negated by sT-ADC. The best sT-ADC cut-offs to predict cancer aggressiveness
      in the development cohort worked in the validation cohort compared to the
      development cohort. CONCLUSION: Standardized ADC overcomes the incompatibility
      between different MRI protocols.

PMID- 28505507
TI  - The effect of pH and heat treatments on the foaming properties of purified alpha
      lactalbumin from camel milk.
AB  - The effect of pH (4.3 or 6.5) and heat treatment (70 degrees C or 90 degrees C
      for 30min) on the foaming and interfacial properties of alpha-lactalbumin
      extracted from camel milk were studied. The increased temperature treatment
      changed the foaming properties of camel alpha-lactalbumin solution and its
      ability to unfold at the air-water interface. At neutral pH, heat treatment was
      found to improve foamability, whereas at acid pH (4.3) this property decreased.
      Foams were more stable after a heat treatment at pH 4.3 than at 6.5, due to
      higher levels of protein aggregation at low pH. Heat treatment at 90 degrees C
      for 30min affected the physicochemical properties of the camel alpha-lactalbumin
      by increasing free thiol group concentration at pH 6.5. Heat treatment also
      caused changes in alpha-lactalbumin's surface charge. These results also confirm
      the pronounced aggregation of heated camel alpha-lactalbumin solution at acid pH.

PMID- 28505508
TI  - Phosphatase activities of a microepiphytic community during a bloom of Ostreopsis
      cf. ovata in the northern Adriatic Sea.
AB  - It is becoming more apparent that increased organic nutrient loads deriving from
      anthropogenic activities and natural processes frequently cause the
      eutrophication of coastal waters. Concurrently, an increasing number of
      phototrophs have been shown to make use of organic nutrients, mainly through
      indirect studies of surface enzyme activities or through direct studies of growth
      in media containing organic-only nutrients. The potential utilization of
      dissolved organic phosphorus (DOP) by microepiphytic-mats associated with
      frequently problematic, toxic dinoflagellate Ostreopsis cf. ovata, was
      investigated throughout a full cycle of a bloom that occurs annually (over the
      last few decades) during summer along several stretches of the Mediterranean
      coast. Measurements of phosphomonoesterase (PMEase) and phosphodiesterase
      (PDEase) activities of the epiphytic mats (including cells and exopolymeric
      substances) and a range of chemico-physical parameters were made from late summer
      to early autumn at a eutrophic site. Analyses of ambient nutrient fractions
      revealed very high aquatic N:P values (TN:TP = 178 +/- 50), very low filterable
      reactive P (FRP) concentrations (13 out 19 under the limits of detection) and DOP
      concentrations that were on average 85% of the total dissolved P. We recorded a
      rapid increase in PMEase and PDEase activities in the epiphytic microalgal
      community that coincided with the onset of a proliferation of the Ostreopsis
      population. Chromogenic staining of samples showed that activity was closely
      associated with the Ostreopsis cells, located both extracellularly (cell surface
      and within the EPS) and intracellularly (ventral cytoplasm). The increase in both
      phosphatases indicates that Ostreopsis can utilise a wide range of DOP types. The
      intense activity in the EPS was suggested to aid in the efficient entrapment and
      processing of high concentration nutrient pulses, for extracellular processing of
      larger organic materials and to prevent loss of substrates and products to the
      surrounding water. Based on the present findings, Ostreopsis seems to have
      adaptations that allow it to thrive in P-limited environments where organic P is
      the main source of P.

PMID- 28505509
TI  - Fungal biocatalyst activated by an electric field: Improved mass transfer and non
      specificity for hydrocarbon degradation in an airlift bioreactor.
AB  - The combination of biological and electrochemical techniques enhances the
      bioremediation efficiency of treating oil-contaminated water. In this study a non
      growing fungal whole cell biocatalyst (BC; Aspergillus brasiliensis attached to
      perlite) pretreated with an electric field (EF), was used to degrade a
      hydrocarbon blend (hexadecane-phenanthrene-pyrene; 100:1:1w/w) in an airlift
      bioreactor (ALB). During hydrocarbon degradation, all mass transfer resistances
      (internal and external) and sorption capacity were experimentally quantified.
      Internal mass transfer resistances were evaluated through BC effectiveness factor
      analysis as a function of the Thiele modulus (using first order reaction
      kinetics, assuming a spherical BC, five particle diameters). External
      (interfacial) mass transfer resistances were evaluated by kLa determination. EF
      pretreatment during BC production promoted surface changes in BC and production
      of an emulsifier protein in the ALB. The BC surface modifications enhanced the
      affinity for hydrocarbons, improving hydrocarbon uptake by direct contact. The
      resulting emulsion was associated with decreased internal and external mass
      transfer resistances. EF pretreatment effects can be summarized as: a combined
      uptake mechanism (direct contact dominant followed by emulsified form dominant)
      diminishing mass transfer limitations, resulting in a non-specific hydrocarbon
      degradation in blend. The pretreated BC is a good applicant for oil-contaminated
      water remediation.

PMID- 28505510
TI  - A potential mechanism for degradation of 4,5-dichloro-2-(n-octyl)-3[2H]
      isothiazolone (DCOIT) by brown-rot fungus Gloeophyllum trabeum.
AB  - This study aims to investigate the biodegradation of 4,5-dichloro-2-(n-octyl)
      3[2H]-isothiazolone (DCOIT) by a brown-rot fungus Gloeophyllum trabeum as well as
      the involved mechanism. In the present study, the retentions of DCOIT in treated
      Masson pine (Pinus massoniana) (MP) chips were determined periodically after
      incubation with G. trabeum. Then a Fenton-like reaction, known as the chelator
      mediated Fenton (CMF) chemistry was used to degrade DCOIT that mimics the
      degradation pathway of DCOIT by typical brown-rot fungi, and the degradation
      intermediates were further analyzed. The results demonstrated that DCOIT was
      rapidly depleted in the early stages of incubation by G. trabeum. The CMF
      treatment was shown to oxidatively decompose DCOIT by producing reactive oxygen
      species. This evidence suggests that the CMF chemistry employed by brown-rot
      fungi contributes to the rapid depletion of DCOIT during G. trabeum exposure,
      although this does not rule out other possible mechanisms for the biodegradation
      of DCOIT. The new findings give new insights into the mechanism for the
      biodegradation of organic biocides, and potentially provide an efficient approach
      for the removal of organic pollutants in the contaminated water.

PMID- 28505511
TI  - Novel electrodialysis cation exchange membrane prepared by 2-acrylamido-2
      methylpropane sulfonic acid; heavy metal ions removal.
AB  - In the present work a novel heterogeneous cation exchange membrane (CEM) composed
      of poly vinyl chloride (PVC) and 2-acrylamido-2-methylpropane sulfonic acid based
      hydrogel (AMAH) was prepared. The membranes were fabricated with different
      fractions of AMAH to optimize the performance in desalination. The hydrogel was
      characterized by FT-IR to prove the successful synthesis. The membrane properties
      such as permselectivity, ionic permeability, flux, water content, electrical
      resistance, morphology, contact angle and dimensional stability were evaluated.
      Modified membranes showed acceptable dimensional stabilities, more hydrophilic
      surface, higher water content and porosity. SEM images revealed the formation of
      a more porous membrane structure. Membrane permselectivity and transport number
      showed a relatively constant then decreasing trend in Na+ and Ba2+ solutions. The
      experimental results showed that the incorporation of AMAH into the PVC matrix
      obviously improved ionic permeability and flux of Na (~9%) and Ba (~23%).
      Membrane electrical resistance was declined about 36% by adding AMAH in the
      membrane structure. Membranes' performance in potassium and heavy metal ions
      removal showed a remarkable separation capacity of K+ (99.9%), Pb2+ (99.9%) and
      Ni2+ (96.9%). Membranes showed desirable potential for scaling removal.

PMID- 28505512
TI  - Identifying the impacts of climate on the regional transport of haze pollution
      and inter-cities correspondence within the Yangtze River Delta.
AB  - Regional haze pollution has become an important environmental issue in the
      Yangtze River Delta (YRD) region. Regional transport and inter-influence of PM2.5
      among cities occurs frequently as a result of the subtropical monsoon climate.
      Backward trajectory statistics indicated that a north wind prevailed from October
      to March, while a southeast wind predominated from May to September. The temporal
      relationships of carbon and nitrogen isotopes among cities were dependent on the
      prevailing wind direction. Regional PM2.5 pollution was confirmed in the YRD
      region by means of significant correlations and similar cyclical characteristics
      of PM2.5 among Lin'an, Ningbo, Nanjing and Shanghai. Granger causality tests of
      the time series of PM2.5 values indicate that the regional transport of haze
      pollutants is governed by prevailing wind direction, as the PM2.5 concentrations
      from upwind area cities generally influence that of the downwind cities.
      Furthermore, stronger correlation coefficients were identified according to
      monsoon pathways. To clarify the impacts of the monsoon climate, a vector
      autoregressive (VAR) model was introduced. Variance decomposition in the VAR
      model also indicated that the upwind area cities contributed significantly to
      PM2.5 in the downwind area cities. Finally, we attempted to predict daily PM2.5
      concentrations in each city based on the VAR model using data from all cities and
      obtained fairly reasonable predictions. These indicate that statistical methods
      of the Granger causality test and VAR model have the potential to evaluate inter
      influence and the relative contribution of PM2.5 among cities, and to predict
      PM2.5 concentrations as well.

PMID- 28505513
TI  - Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991-2012.
AB  - BACKGROUND: Industrial discharges of perfluorooctanoic acid (PFOA) to the Ohio
      River, contaminating water systems near Parkersburg, WV, were previously
      associated with nearby residents' serum PFOA concentrations above US general
      population medians. Ohio River PFOA concentrations downstream are elevated,
      suggesting Mid-Ohio River Valley residents are exposed through drinking water.
      OBJECTIVES: Quantify PFOA and 10 other per- and polyfluoroalkyl substances (PFAS)
      in Mid-Ohio River Valley resident sera collected between 1991 and 2013 and
      determine whether the Ohio River and Ohio River Aquifer are exposure sources.
      METHODS: We measured eleven PFAS in 1608 sera from 931 participants. Serum PFOA
      concentration and water source associations were assessed using linear mixed
      effects models. We estimated between-sample serum PFOA using one-compartment
      pharmacokinetics for participants with multiple samples. RESULTS: In serum
      samples collected as early as 1991, PFOA (median = 7.6 ng/mL) was detected in
      99.9% of sera; 47% had concentrations greater than US population 95th
      percentiles. Five other PFAS were detected in greater than 82% of samples; median
      other PFAS concentrations were similar to the US general population. Serum PFOA
      was significantly associated with water source, sampling year, age at sampling,
      tap water consumption, pregnancy, gravidity and breastfeeding. Serum PFOA was 40
      60% lower with granular activated carbon (GAC) use. Repeated measurements and
      pharmacokinetics suggest serum PFOA peaked 2000-2006 for participants using water
      without GAC treatment; where GAC was used, serum PFOA concentrations decreased
      from 1991 to 2012. CONCLUSIONS: Mid-Ohio River Valley residents appear to have
      PFOA, but not other PFAS, serum concentrations above US population levels.
      Drinking water from the Ohio River and Ohio River Aquifer, primarily contaminated
      by industrial discharges 209-666 km upstream, is likely the primary exposure
      source. GAC treatment of drinking water mitigates, but does not eliminate, PFOA
      exposure.

PMID- 28505514
TI  - TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which
      decreases in contact hypersensitivity.
AB  - Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing
      immune responses and a splenic CD5+CD1dhi Breg subset identified earlier was
      shown to exert its regulatory functions through secretion of IL-10. Though FasL
      expression is an alternative mechanism of immune suppression used by B cells,
      little is known about the FasL expressing CD5+CD1dhi Bregs. In this study, we
      isolated splenocytes or splenic CD19+ B cells and compared the efficiency of toll
      like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40
      and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5+CD1dhi
      Bregs by flow cytometry. FasL expression in CD5+CD1dhi B cells was rapidly
      increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40
      combinations failed to stimulate FasL expression in CD5+CD1dhi B cells although
      the IL-10 production was up-regulated in this subset. In addition, LPS and other
      B10-cell inducers increased the expression of surface molecules like CD86 and
      CD25, which are correlated to the regulatory functions of B cells. Furthermore,
      NF-kappaB and NF-AT inhibitors decreased the TLR4-activated FasL expression in
      CD5+CD1dhi B cells. Then we sorted splenic CD5+CD1dhi Bregs using flow cytometry
      and found that TLR4-activated CD5+CD1dhi Bregs suppressed the proliferation of
      CFSE-labeled CD4+ T cells in vitro, which was partly blocked by anti-FasL
      antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL
      expression in splenic CD5+CD1dhi B cells was decreased compared to the control
      group after TLR4 ligation. Our findings suggest that the regulatory function of
      CD5+CD1dhi B cells could be partly mediated by Fas-FasL pathway and this FasL
      expressing CD5+CD1dhi Bregs might participate in the regulation of inflammatory
      diseases.

PMID- 28505515
TI  - RhoB induces the production of proinflammatory cytokines in TLR-triggered
      macrophages.
AB  - Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular
      patterns on microorganisms, thus acting as important components of innate
      immunity against invading pathogens. Many positive and negative regulators of TLR
      triggered signaling have been identified. The Rho GTPase RhoB plays a key role in
      cell migration, division and polarity; however, the function and regulatory
      mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be
      investigated. Here, we report that the expression of RhoB is induced by TLR
      agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages. Knockdown of
      RhoB expression markedly decreased TLR ligand-induced activation of mitogen
      activated protein kinases and nuclear factor-kappaB (NF-kappaB), and the
      production of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL
      1beta in macrophages stimulated with TLR ligands. Furthermore, we demonstrated
      that RhoB interacts with major histocompatibility complex class II (MHCII) alpha
      chain, but not beta chain, in endosomes of macrophages. Knockdown of MHCII
      expression greatly reduced the interaction of RhoB with Btk, and attenuated the
      induction of NF-kappaB and interferon beta activity by RhoB upon LPS stimulation.
      These findings suggest that RhoB is a positive physiological regulator of TLRs
      signaling via binding to MHCII in macrophages, and therefore RhoB may be a
      potential therapeutic target in inflammatory diseases.

PMID- 28505516
TI  - Induction of experimental autoimmune orchitis by immunization with xenogenic
      testicular germ cells in mice.
AB  - We previously showed that immunization of mice with syngeneic or allogeneic
      testicular germ cells (TGC) alone induces autoimmune inflammation in the testes
      without using any adjuvant. In the present study, we examined testicular
      autoimmune response against xenogenic TGC antigens in mice. The mice were
      immunized with murine, rat or guinea pig TGC and then the histopathology, delayed
      type hypersensitivity (DTH) response and humoral autoimmunity were investigated.
      The results showed that immunization with not only murine but also rat TGC caused
      experimental autoimmune orchitis (EAO) with hypospermatogenesis in mice, while
      that with guinea pig TGC could not. The DTH response to murine TGC was
      significantly elevated in mice that had been immunized with murine or rat but not
      guinea pig TGC. Serum autoantibody to murine TGC was immunohistochemically
      detected in the mice immunized with either murine, rat or guinea pig TGC,
      however, the level of autoantibody detected by ELISA revealed significant
      elevation when mice were immunized with murine and rat TGC. With the
      immunoblotting after electrophoresis, the murine TGC proteins at molecular masses
      around 55kDa and 70kDa can be detected when incubated with sera from m-TGC and r
      TGC groups. These results represent the cross-reactivity among TGC of the mouse,
      the rat and the guinea pig at the levels of humoral immunity and also demonstrate
      that the rat TGC could elicit significant DTH response to murine TGC with the
      resultant EAO. This is the first to succeed in EAO induction by the use of
      xenogenic TGC.

PMID- 28505517
TI  - A Modified Adenovirus Vector-Mediated Antibody Screening Method Identifies EphA2
      as a Cancer Target.
AB  - BACKGROUND: We constructed a genetically modified adenovirus vector incorporating
      an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33
      allows an antibody to redirect the vector to a target molecule on the cell
      surface. We attempted to search for target antigen candidates and antibodies that
      allowed highly selective gene transduction into malignant tumors. METHODS:
      Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that
      increased transduction efficiency in cancer cell lines after cross-linking with
      Adv-FZ33. Target antigens of the mAbs were identified by immunoprecipitation and
      mass spectrometry. Of these mAbs, we noted a clone, F2-27, that recognized the
      receptor tyrosine kinase EphA2. Next, we generated an adenovirus vector, Ax3CMTK
      FZ33, that expressed a herpes simplex virus thymidine kinase (HSV-TK). The
      therapeutic efficacy of F2-27-mediated HSV-TK gene transduction, followed by
      ganciclovir (GCV) administration, was studied in vitro. The inhibitory effect of
      F2-27 on cancer cell invasion was investigated by a three-dimensional spheroid
      formation assay. RESULTS: In vitro reporter gene expression after Adv-FZ33
      infection via F2-27 was 146 times higher than with control mAb in EphA2
      expressing cancer cell lines. F2-27-mediated Ax3CMTK-FZ33 infection induced the
      HSV-TK gene in an F2-27-dependent manner and had a highly effective cytotoxic
      effect in a GCV-dependent manner. Additionally, F2-27 independently inhibited
      migration of EphA2-positive breast cancer cell lines in three-dimensional
      culture. CONCLUSION: Our modified adenovirus and hybridoma screening system is
      useful for the development of targeted cancer therapy, and F2-27 has the
      potential to be an antibody-based therapy for various EphA2-positive cancers.

PMID- 28505518
TI  - Registered nurse buddies: Educators by proxy?
AB  - The informal clinical teaching role of the buddy nurse seems to be a uniquely
      Australian title, with little consistency in terminology for informal nurse
      educator roles internationally. Not all registered nurses are professionally
      developed for the informal role of facilitating the clinical learning of students
      in clinical settings, yet these roles are expected by nursing professional
      bodies. In Australia the registered nurses (RN) experience of being a buddy nurse
      has been reported as lacking clarity, being unsupported and structureless. Whist
      there is a plethora of literature published about formal RN educator roles,
      little is available on the informal buddy nurse role. A view of the buddy nurse
      role in reference to the limited but available literature in the Australian
      context is offered in this paper. International perspectives are also gathered
      describing informal clinical education RN's roles with similar responsibilities
      to the Australian buddy nurse. The significance of this dialogue is to ignite
      debate about the role, potentially informing policy for the improved support of
      the role within the Australian nursing landscape.

PMID- 28505519
TI  - Impact of interactive situated and simulated teaching program on novice nursing
      practitioners' clinical competence, confidence, and stress.
AB  - BACKGROUND: Novice nursing practitioners (NNPs) often struggle to make the
      transition to fully competent professionals. We sought to determine the impact of
      an interactive, situated learning workshop on a participant's clinical
      competence. OBJECTIVES: This work aimed to improve the clinical competence,
      promote the self-confidence, and reduce the number of work-related stressors of
      NNPs. METHODS: We randomly allocated 31 newly graduated NNPs into interactive
      situated and simulated teaching (ISST) and non-ISST groups, which were perceived
      as the homogeneity of the 2 groups based upon no significant difference at age,
      education level and work units. The ISST program comprised six follow-up
      interactive face-to-face support sessions over a three-month period following the
      standard orientation training course. We assessed the participants' competency,
      stress, and confidence levels in professional competence before and at the end of
      the study. RESULTS: At the end of the three-month study period, the ISST group
      demonstrated superior nursing competency (p=0.001), as well as reported lower
      stress levels (p=0.011), and increased confidence in professional competence
      (p=0.026) as compared with those in the control group. A multiple regression
      analysis revealed that clinical nursing competence was positively correlated with
      the use of ISST (p=0.02) and negatively correlated with stress (p=0.03).
      CONCLUSIONS: The ISST program for NNPs significantly improved their clinical
      competence. It may be helpful to ensure that new trainees have access to training
      programs that can facilitate their acclimation to their new working environments
      at the beginning of their careers.

PMID- 28505520
TI  - Nursing program evaluation for Nurse Educators.

PMID- 28505521
TI  - Short simulation exercises to improve emergency department nurses' self-efficacy
      for initial disaster management: Controlled before and after study.
AB  - INTRODUCTION: Head nurses at emergency departments often assume responsibility
      for managing the initial response to a major incident, and to create surge
      capacity. Training is essential to enable these nurses to perform an effective
      disaster response. Evaluating the effects of such training is however complicated
      as real skill only can be demonstrated during a real major incident. Self
      efficacy has been proposed as an alternative measure of training effectiveness.
      PURPOSE: The aim of this study was to examine if short, small-scale computer
      based simulation exercises could improve head emergency nurses' general and
      specific self-efficacy and initial incident management skills. METHOD: A within
      group pretest-posttest design was used to examine 13 head nurses' general and
      specific self-efficacy before and after an intervention consisting of three short
      computer based simulation exercises during a 1-h session. Management skills were
      assessed using the computer simulation tool DigEmergo. RESULTS: The exercises
      increased the head nurses' general self-efficacy but not their specific self
      efficacy. After completing the first two exercises they also exhibited improved
      management skills as indicated by shorter time to treatment for both trauma and
      in-hospital patients. CONCLUSION: This study indicates that short computer based
      simulation exercises provide opportunities for head nurses to improve management
      skills and increase their general self-efficacy.

PMID- 28505522
TI  - The Knowledge-about-Older-Patients - Quiz (KOP-Q) for nurses: Cross-cultural
      validation between the Netherlands and United States of America.
AB  - BACKGROUND: The Knowledge about Older Patients-Quiz (KOP-Q) is designed as a
      unidimensional scale measuring knowledge of hospital nurses about older patients.
      Furthermore, the KOP-Q measures a second unidimensional construct, certainty of
      hospital nurses about their knowledge. The KOP-Q is developed and validated in
      the Netherlands. Whether the KOP-Q can be used in other countries is unknown
      given the cultural and language differences. OBJECTIVES: Investigate the level of
      measurement invariance of the KOP-Q between the Netherlands and United States of
      America (USA). DESIGN: A multicenter international cross-sectional design.
      SETTINGS: Four general hospitals in the Netherlands and four general hospitals in
      the USA. PARTICIPANTS: Nurses from the Netherlands (n=201) and the USA (n=130)
      were invited to participate by email from the ward manager, distributing flyers
      and present messages on the online hospital communication boards. Questions of
      the KOP-Q were completed online. METHOD: The level of measurement invariance
      (configural, metric or scalar invariance) across countries was tested by running
      increasingly constrained structural equation models, and testing whether these
      models fitted the data. RESULTS: Both the knowledge and certainty construct of
      the KOP-Q proved unidimensional in the Netherlands and USA sample. Test results
      of the measurement invariance across the Netherlands and USA indicated a stable,
      partial scalar invariance (15 items full scalar invariance) for the knowledge
      items and full scalar invariance for the certainty items. CONCLUSIONS: The KOP-Q
      shows to function uniformly across both language groups and can therefore be used
      to assess nurses' knowledge and their certainty about this knowledge which can be
      important for educational and/or quality improvement programs in the USA.
      Furthermore, the KOP-Q is suitable to make comparisons between the Netherlands
      and the USA using latent variable models. Before the KOP-Q can be used in other
      countries, cross-cultural tests should again be performed.

PMID- 28505523
TI  - Trainers' perception of the learning environment and student competency: A
      qualitative investigation of midwifery and anesthesia training programs in
      Ethiopia.
AB  - BACKGROUND: Ethiopia has successfully expanded training for midwives and
      anesthetists in public institutions. This study explored the perceptions of
      trainers (instructors, clinical lab assistants and preceptors) towards the
      adequacy of students' learning experience and implications for achieving mastery
      of core competencies. METHODS: In-depth interviews with 96 trainers at 9 public
      universities and 17 regional health science colleges across Ethiopia were
      conducted to elicit their opinions about available resources, program curriculum
      suitability, and competence of graduating students. Using Dedoose, data were
      thematically analyzed using grounded theory. RESULTS: Perceptions of anesthesia
      and midwifery programs were similar. Common challenges included unpreparedness
      and poor motivation of students, shortages of skills lab space and equipment,
      difficulties ensuring students' exposure to sufficient and varied enough cases to
      develop competence, and lack of coordination between academic training
      institutions and clinical attachment sites. Additional logistical barriers
      included lack of student transport to clinical sites. Informants recommended
      improved recruitment strategies, curriculum adjustments, increased time in skills
      labs, and better communication across academic and clinical sites. CONCLUSIONS:
      An adequate learning environment ensures that graduating midwives and
      anesthetists are competent to provide quality services. Minimizing the human
      resource, infrastructural and logistical gaps identified in this study requires
      continued, targeted investment in health systems strengthening.

PMID- 28505525
TI  - Thrombin generation and intracranial atherosclerotic disease in patients with a
      transient ischaemic attack.
AB  - BACKGROUND: Intracranial atherosclerotic disease (ICAD) is responsible for at
      least 10% of transient ischaemic attacks (TIA). Thrombin generation has been
      shown to be associated with several atherosclerotic conditions and may be
      relevant in the pathogenesis of TIA from ICAD. OBJECTIVE: To evaluate the
      association between thrombin generation and ICAD in patients with TIA. MATERIALS
      AND METHODS: Consecutive patients with confirmed diagnosis of TIA by vascular
      neurologist were enrolled. Within 24h from diagnosis, all the patients underwent:
      blood samples including thrombin generation search, electrocardiography, brain CT
      scan, blood pressure (BP) measurement, supra-aortic echo-Doppler, transcranial
      Doppler (TCD) and standard echocardiogram. Thrombin generation was measured as
      endogenous thrombin potential (ETP) in platelet-rich plasma (PRP) and in platelet
      poor plasma (PPP), in the presence and in the absence of thrombomodulin (TM).
      RESULTS: 120 patients (male 52.5%), aged 69+/-16years were enrolled. Ten patients
      on warfarin treatment had significantly lower ETP than the others. Among the
      remaining, ETP in the presence or absence of TM did not differ according to TOAST
      classification aetiology (large vessel vs. cardioembolic vs. lacunar vs. others).
      In PRP, ETP was similar in patients with ICAD and in those without (1748+/-160
      vs. 1851+/-36nM.min, p=0.393), whereas, ETP measured in presence of
      thrombomodulin was higher in patients with than in those without ICAD (2045+/-99
      vs. 1715+/-41nM.min, p=0.011). In PPP, ETP was similar in patients with ICAD and
      in those without, whereas thrombin peak was higher in patients with ICAD than in
      those without both in the presence (165+/-17 vs. 130+/-5nM, p=0.036) and in the
      absence of TM (178+/-19 vs. 142+/-5nM, p=0.037). CONCLUSION: ETP measured in
      presence of TM is enhanced in patients with ICAD, supporting that thrombomodulin
      protein C pathways is relevant in TIA from ICAD. These hypothesis-generating data
      suggest that thrombin generation may be relevant in cerebral ischaemia from
      intracranial disease, and justify larger studies.

PMID- 28505526
TI  - Peripheral hearing loss reduces the ability of children to direct selective
      attention during multi-talker listening.
AB  - Restoring normal hearing requires knowledge of how peripheral and central
      auditory processes are affected by hearing loss. Previous research has focussed
      primarily on peripheral changes following sensorineural hearing loss, whereas
      consequences for central auditory processing have received less attention. We
      examined the ability of hearing-impaired children to direct auditory attention to
      a voice of interest (based on the talker's spatial location or gender) in the
      presence of a common form of background noise: the voices of competing talkers
      (i.e. during multi-talker, or "Cocktail Party" listening). We measured brain
      activity using electro-encephalography (EEG) when children prepared to direct
      attention to the spatial location or gender of an upcoming target talker who
      spoke in a mixture of three talkers. Compared to normally-hearing children,
      hearing-impaired children showed significantly less evidence of preparatory brain
      activity when required to direct spatial attention. This finding is consistent
      with the idea that hearing-impaired children have a reduced ability to prepare
      spatial attention for an upcoming talker. Moreover, preparatory brain activity
      was not restored when hearing-impaired children listened with their acoustic
      hearing aids. An implication of these findings is that steps to improve auditory
      attention alongside acoustic hearing aids may be required to improve the ability
      of hearing-impaired children to understand speech in the presence of competing
      talkers.

PMID- 28505527
TI  - Amino acid and acetylcholine chemistry in the central auditory system of young,
      middle-aged and old rats.
AB  - Older adults generally experience difficulties with hearing. Age-related changes
      in the chemistry of central auditory regions, especially the chemistry underlying
      synaptic transmission between neurons, may be of particular relevance for hearing
      changes. In this study, we used quantitative microchemical methods to map
      concentrations of amino acids, including the major neurotransmitters of the
      brain, in all the major central auditory structures of young (6 months), middle
      aged (22 months), and old (33 months old) Fischer 344 x Brown Norway rats. In
      addition, some amino acid measurements were made for vestibular nuclei, and
      activities of choline acetyltransferase, the enzyme for acetylcholine synthesis,
      were mapped in the superior olive and auditory cortex. In old, as compared to
      young, rats, glutamate concentrations were lower throughout central auditory
      regions. Aspartate and glycine concentrations were significantly lower in many
      and GABA and taurine concentrations in some cochlear nucleus and superior olive
      regions. Glutamine concentrations and choline acetyltransferase activities were
      higher in most auditory cortex layers of old rats as compared to young. Where
      there were differences between young and old rats, amino acid concentrations in
      middle-aged rats often lay between those in young and old rats, suggesting
      gradual changes during adult life. The results suggest that hearing deficits in
      older adults may relate to decreases in excitatory (glutamate) as well as
      inhibitory (glycine and GABA) neurotransmitter amino acid functions. Chemical
      changes measured in aged rats often differed from changes measured after
      manipulations that directly damage the cochlea, suggesting that chemical changes
      during aging may not all be secondary to cochlear damage.

PMID- 28505524
TI  - Inactivated influenza virus vaccines: the future of TIV and QIV.
AB  - Influenza viruses continue to be a major public health concern, despite the
      availability of vaccines. Currently licensed influenza vaccines aim at the
      induction of antibodies that target hemagglutinin, the major antigenic
      determinant on the surface of influenza virions that is responsible for
      attachment of the virus to the host cell that is to be infected. Currently
      licensed influenza vaccines come as inactivated or live attenuated influenza
      vaccines and are trivalent or quadrivalent as they contain antigens of two
      influenza A and one or two influenza B strains that circulate in the human
      population, respectively. In this review we briefly compare trivalent and
      quadrivalent inactivated influenza vaccines (TIV and QIV) with live attenuated
      influenza vaccines (LAIV). The use of the latter vaccine type in children age 2-8
      has been disrecommended recently by the American Centers for Disease Control and
      Prevention due to inferior vaccine effectiveness in this age group in recent
      seasons. This recommendation will favor the use of TIV and QIV over LAIV in the
      near future. However, there is much evidence from studies in humans that
      illustrate the benefit of LAIV and we discuss some of the mechanisms that
      contribute to broader protection against influenza viruses of different subtypes
      induced by natural infection and LAIV. The future challenge will be to apply
      these insights to allow induction of broader and long-lasting protection provided
      by TIV and QIV vaccines, for example, by the use of adjuvants or combining LAIV
      with TIV and QIV. Other immune factors than serum hemagglutination inhibiting
      antibodies have shown to correlate with protection provided by TIV and QIV, which
      illustrates the need for other correlates of protection than hemagglutination
      inhibition by serum antibodies and justifies more focus on influenza antigens in
      the TIV and QIV other than hemagglutinin.

PMID- 28505528
TI  - Acuity in ranging based on delay-tuned combination-sensitive neurons in the
      auditory cortex of mustached bats.
AB  - A 1.0-ms echo delay from an emitted bio-sonar pulse at 25  degrees C corresponds
      to a 17.3-cm target distance. In the auditory cortex of the mustached bat,
      Pteronotus parnellii, neurons tuned to a specific delay (best delay) of an echo
      from an emitted pulse are clustered in the FF, dorsal fringe and ventral fringe
      areas. ("FF" stands for the frequency-modulated components of a pulse and its
      echo.) Those delay-tuned neurons are systematically arranged in the FF area
      according to their best delays and form a 18-ms-long delay axis. Using the
      neurophysiological data, the theoretical acuity at a 75% correct level was
      computed as just-noticeable changes in (a) the location of maximally responding
      delay-tuned neurons, (b) the location of the center of all responses in the FF
      area, and (c) the weighted sum of responses of all delay-tuned neurons. The
      acuity is range-dependent: the shorter the target range, the higher the acuity
      is. The just-noticeable changes in target range are 7.57-46.2, 0.50-2.32 and 0.22
      2.53 mm at the target ranges of up to 140 cm for (a), (b) and (c), respectively.
      When the dorsal and ventral fringe areas are included in the computation, the
      just-noticeable changes become smaller than those in the FF area alone. Those
      acuities computed are comparable to certain behavioral acuities.

PMID- 28505529
TI  - Influence of Bisphenol A on the transport and deposition behaviors of bacteria in
      quartz sand.
AB  - The influence of Bisphenol A (BPA) on the transport and deposition behaviors of
      bacteria in quartz sand was examined in both NaCl (10 and 25 mM) and CaCl2
      solutions (1.2 and 5 mM) by comparing the breakthrough curves and retained
      profiles of cell with BPA in suspensions versus those without BPA. Gram-negative
      Escherichia coli and Gram-positive Bacillus subtilis were employed as model cells
      in the present study. The extended Derjaguin-Landau-Verwey-Overbeek interaction
      energy calculation revealed that the presence of BPA in cell suspensions led to a
      lower repulsive interaction between the cells and the quartz sand. This suggests
      that, theoretically, increased cell deposition on quartz sand would be expected
      in the presence of BPA. However, under all examined solution conditions, the
      presence of BPA in cell suspensions increased transport and decreased deposition
      of bacteria in porous media regardless of cell type, ionic strength, ion valence,
      the presence or absence of extracellular polymeric substances. We found that
      competition by BPA through hydrophobicity for deposition sites on the quartz sand
      surfaces was the sole contributor to the enhanced transport and decreased
      deposition of bacteria in the presence of BPA.

PMID- 28505530
TI  - Photocatalytic wastewater purification with simultaneous hydrogen production
      using MoS2 QD-decorated hierarchical assembly of ZnIn2S4 on reduced graphene
      oxide photocatalyst.
AB  - It is attractive to photocatalytically purify wastewater and simultaneously
      convert solar energy into clean hydrogen energy. However, it is still a challenge
      owing to the relatively low photocatalytic efficiency of photocatalysts. In this
      study, we synthesized a molybdenum disulfide (MoS2) quantum dot-decorated 3D
      nanoarchitecture (MoS2QDs) of indium zinc sulfide (ZnIn2S4) and reduced grapheme
      oxide (MoS2QDs@ZnIn2S4@RGO) photocatalyst using a simple solvothermal method. The
      RGO promotes the electron transfer, and the highly dispersed MoS2QDs provides
      numerous catalytic sites. The photocatalytic purification of rhodamine B (RhB),
      eosin Y (EY), fulvic acid (FA), methylene blue (MB) and p-nitrophenol (PNP) in
      simulated wastewaters were further tested. The degradation efficiencies and TOC
      removal were 91% and 75% for PNP, 92.2% and 72% for FA, 98.5% and 80% for MB,
      98.6% and 84% for EY, and 98.8% and 88% for RhB, respectively (Corganics = 20
      mg/L, Ccatalyst = 1.25 g/L, t = 12 h, Ilight = 3.36 * 10-5 E L-1 s-1). Among
      these tests, the highest hydrogen production was achieved (45 MUmol) during RhB
      degradation. Both experimental and calculational results prove that lower LUMO
      (lowest unoccupied molecular orbit) level of organic molecules was available for
      transferring electrons to catalysts, resulting in more efficient hydrogen
      production. Significantly, the removal efficiencies of natural organic substances
      in actual river water reached 76.3-98.4%, and COD reduced from 32 to 16 mg/L with
      13.8 MUmol H2 production after 12 h.

PMID- 28505531
TI  - Rapid degradation, mineralization and detoxification of pharmaceutically active
      compounds in aqueous solution during pulsed corona discharge treatment.
AB  - In the present study, plasma generated by pulsed corona discharge was used for
      the degradation of diclofenac, carbamazepine and ciprofloxacin. Pollutants in
      aqueous solution were plasma treated under two categories: single and mixed
      pollutant condition. Mixed pollutant condition showed an antagonistic behaviour
      and thus the degradation time was higher for mixed condition compared to the
      single condition. At different voltage and frequencies, degradation efficiency
      followed the trend, diclofenac>carbamazepine>ciprofloxacin. Acidic pH slightly
      favoured the degradation process whereas in presence of radical scavengers (HCO3
      , CO32- and humic acid) the degradation yield was significantly decreased. With
      an input power of 101.5 W, complete degradation was achieved within 4-16 min of
      plasma treatment for pharmaceutical's concentrations of 1-10 mg/L. As the
      pollutant concentration increased from 1 to 10 mg/L, the pseudo first order rate
      constant decreased, while yield increased. Complete degradation pathway of
      diclofenac, carbamazepine and ciprofloxacin in plasma treatment process are
      proposed by identifying the intermediates using LC-MS analysis. TOC analysis
      confirmed 80% mineralization within 10 min of plasma treatment for higher
      pharmaceutical's concentrations of 10 mg/L. The microalgae ecotoxicity study and
      disc diffusion test confirmed the complete detoxification of PACs that took place
      after 6 min of plasma treatment.

PMID- 28505532
TI  - Encapsulated Pseudomonas putida for phenol biodegradation: Use of a structural
      membrane for construction of a well-organized confined particle.
AB  - Phenols are toxic byproducts from a wide range of industry sectors. If not
      treated, they form effluents that are very hazardous to the environment. This
      study presents the use of a Pseudomonas putida F1 culture encapsulated within a
      confined environment particle as an efficient technique for phenol
      biodegradation. The innovative encapsulation technique method, named the "Small
      Bioreactor Platform" (SBP) technology, enables the use of a microfiltration
      membrane constructed as a physical barrier for creating a confined environment
      for the encapsulated culture. The phenol biodegradation rate of the encapsulated
      culture was compared to its suspended state in order to evaluate the
      effectiveness of the encapsulation technique for phenol biodegradation. A maximal
      phenol biodegradation rate (q) of 2.12/d was exhibited by encapsulated P. putida
      at an initial phenol concentration of 100 mg/L. The biodegradation rate decreased
      significantly at lower and higher initial phenol concentrations of 50 and up to
      3000 mg/L, reaching a rate of 0.1018/d. The results also indicate similar and up
      to double the degradation rate between the two bacterial states (encapsulated vs.
      suspended). High resolution scanning electron microscopy images of the SBP
      capsule's membrane morphology demonstrated a highly porous microfiltration
      membrane. These results, together with the long-term activity of the SBP capsules
      and verification that the culture remains pure after 60 days using 16S rRNA gene
      phylogenetic affiliation tests, provide evidence for a successful application of
      this new encapsulation technique for bioaugmentation of selected microbial
      cultures in water treatment processes.

PMID- 28505533
TI  - Discovery and characterization of selective human sphingomyelin synthase 2
      inhibitors.
AB  - Sphingomyelin synthase (SMS) is a membrane enzyme that catalyzes the synthesis of
      sphingomyelin, is required for the maintenance of plasma membrane microdomain
      fluidity, and has two isoforms: SMS1 and SMS2. Although these isoforms exhibit
      the same SMS activity, they are different enzymes with distinguishable
      subcellular localizations. It was reported that SMS2 KO mice displayed lower
      inflammatory responses and anti-atherosclerotic effects, suggesting that
      inhibition of SMS2 would be a potential therapeutic approach for controlling
      inflammatory responses and atherosclerosis. This study aimed to discover a novel
      small-molecule compound that selectively inhibits SMS2 enzymatic activity. We
      developed a human SMS2 enzyme assay with a high-throughput mass spectrometry
      based screening system. We characterized the enzymatic properties of SMS2 and
      established a high-throughput screening-compatible assay condition. To identify
      human SMS2 inhibitors, we conducted compound screening using the enzyme assay. We
      identified a 2-quinolone derivative as a SMS2 selective inhibitor with an IC50 of
      950 nM and >100-fold selectivity for SMS2 over SMS1. The 2-quinolone exhibited
      efficacy in a cell-based engagement assay. We demonstrated that a more potent
      derivative directly bound to SMS2-expressing membrane fractions in an affinity
      selection mass spectrometry assay. Mutational analyses revealed that the
      interaction of the inhibitor with SMS2 required the presence of the amino acids
      S227 and H229, which are located in the catalytic domain of SMS2. In conclusion,
      we discovered novel SMS2-selective inhibitors. 2-Quinolone SMS2 inhibitors are
      considered applicable for leading optimization studies. Further investigations
      using these SMS2 inhibitors would provide validation tools for SMS2-relevant
      pathways in vitro and in vivo.

PMID- 28505534
TI  - Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of
      cholinesterase inhibitors.
AB  - The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3
      dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two
      specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are
      here demonstrated for the first time to be reversible competitive inhibitors of
      cholinesterases. They showed Ki for electric eel acetylcholinesterase of 1.6-15.0
      MUM, for recombinant human acetylcholinesterase of 22.8-98.0 MUM, and for horse
      serum butyrylcholinesterase of 5.0-76.0 MUM. These values are promising when
      compared to the current cholinesterase inhibitors used for treatment of patients
      with Alzheimer's disease, to counteract the acetylcholine deficiency in the
      brain. Good correlation was obtained between IC50 data and results by molecular
      docking calculation on the binding interactions within the acetylcholinesterase
      active site, which also indicated the moieties in discorhabdin structures
      involved. To avoid unwanted peripheral side effects that can appear in patients
      using some acetylcholinesterase inhibitors, electrophysiological experiments were
      carried out on one of the most active of these compounds, discorhabdin G, which
      confirmed that it had no detectable undesirable effects on neuromuscular
      transmission and skeletal muscle function. These findings are promising for
      development of cholinesterase inhibitors based on the scaffold of discorhabdins,
      as potential new agents for treatment of patients with Alzheimer's disease.

PMID- 28505535
TI  - Thiosemicarbazones and 4-thiazolidinones indole-based derivatives: Synthesis,
      evaluation of antiproliferative activity, cell death mechanisms and topoisomerase
      inhibition assay.
AB  - In this study, we report the synthesis and structural characterization of a
      series of thiosemicarbazone and 4-thiazolidinones derivatives, as well as their
      in vitro antiproliferative activity against eight human tumor cell lines. For the
      most potent compound further studies were performed evaluating cell death
      induction, cell cycle profile, ctDNA interaction and topoisomerase IIalpha
      inhibition. A synthetic three-step route was established for compounds (2a-e and
      3a-d) with yields ranging from 32 to 95%. Regarding antiproliferative activity,
      compounds 2a-e and 3a-d showed mean GI50 values ranging between 1.1 MUM (2b) -
      84.65 MUM (3d). Compound 2b was the most promising especially against colorectal
      adenocarcinoma (HT-29) and leukemia (K562) cells (GI50 = 0.01 MUM for both cell
      lines). Mechanism studies demonstrated that 24 h-treatment with compound 2b (5
      MUM) induced phosphatidylserine residues exposition and G2/M arrest on HT-29
      cells. Moreover, 2b (50 MUM) was able to interact with ctDNA and inhibited
      topoisomerase IIalpha activity. These results demonstrate the importance of
      thiosemicarbazone, especially the derivative 2b, as a promising candidate for
      anticancer therapy.

PMID- 28505536
TI  - Design, synthesis, molecular docking and cytotoxic evaluation of novel 2
      furybenzimidazoles as VEGFR-2 inhibitors.
AB  - Inhibition of angiogenesis through inhibition of vascular endothelial growth
      factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its
      important role in promoting cancer growth and metastasis. In the presented study,
      a series of benzimidazol-furan hybrids was designed and synthesized through
      facile synthetic pathways. Evaluation of the synthesized compounds for their in
      vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2)
      carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and
      15, showed potent antiproliferative properties against MCF-7 cell line (IC50 =
      21.25, 21.35 MUM, respectively) in comparison to tamoxifen (IC50 = 21.57 MUM).
      Additionally, compounds 10a, 10b, 15 and 17 showed promising potency (IC50 =
      25.95, 22.58, 26.94 and 31.06 MUM, respectively) against liver carcinoma cell
      line HepG2 in contrast to cisplatin (IC50 = 31.16 MUM). Moreover, in vitro
      evaluation of the synthesized compounds for their effect on the level of VEGFR-2
      in MCF-7 cell line showed their potent inhibitory activity relative to control
      untreated cells. Four compounds 10a, 10b, 14 and 15 showed 92-96% reduction in
      VEGFR-2 level, compared with tamoxifen and sorafenib which showed inhibition
      percentage of 98% and 95.75%, respectively. Compound 10a was found to have
      promising VEGFR-2 inhibitory activity (IC50 = 0.64 MUM) in comparison to
      sorafenib (IC50 = 0.1 MUM). Molecular docking was performed to study the binding
      pattern of the newly synthesized compounds with VEGFR-2 active site. Molecular
      docking attributed their good VEGFR-2 inhibitory activity to their hydrogen
      bonding interaction with the key amino acids in VEGFR-2 active site, Glu885 and
      Asp1046, and their hydrophobic interaction by their 2-furylbenzimidazole moiety
      with the allosteric hydrophobic back pocket in a type III inhibitors-like binding
      mode. The binding interaction is augmented by a ring substituent with long chain
      extension at position 1 of the benzimidazole due to its hydrophobic interaction
      with the hydrophobic side chains of the amino acids at the interface between the
      ATP binding site and the allosteric back pocket. Structure-activity relationship
      (SAR) was inferred for future optimization based on the performed biological and
      docking studies.

PMID- 28505537
TI  - Investigation of pyrazolo-sulfonamides as putative small molecule oxytocin
      receptor agonists.
AB  - The neuropeptide oxytocin has been implicated in multiple central nervous system
      functions in mammalian species. Increased levels have been reported to improve
      trust, alleviate symptoms related to autism and social phobias, and reduce social
      anxiety. Hoffman-La Roche published a patent claiming to have found potent small
      molecule oxytocin receptor agonists, smaller than the first non-peptide oxytocin
      agonist reported, WAY 267,464. We selected two of the more potent compounds from
      the patent and, in addition, created WAY 267,464 hybrid structures and determined
      their oxytocin and vasopressin receptor activity. Human embryonic kidney and
      Chinese hamster ovary cells were used for the expression of oxytocin or
      vasopressin 1a receptors and activity assessed via IP1 accumulation assays and
      calcium FLIPR assays. The results concluded that the reported compounds in the
      patent and the hybrid structures have no activity at the oxytocin or vasopressin
      1a receptors.

PMID- 28505538
TI  - Synthesis and pharmacological evaluation of neurosteroid photoaffinity ligands.
AB  - Neuroactive steroids are potent positive allosteric modulators of GABAA receptors
      (GABAAR), but the locations of their GABAAR binding sites remain poorly defined.
      To discover these sites, we synthesized two photoreactive analogs of alphaxalone,
      an anesthetic neurosteroid targeting GABAAR, 11beta-(4-azido-2,3,5,6
      tetrafluorobenzoyloxy)allopregnanolone, (F4N3Bzoxy-AP) and 11-aziallopregnanolone
      (11-AziAP). Both photoprobes acted with equal or higher potency than alphaxalone
      as general anesthetics and potentiators of GABAAR responses, left-shifting the
      GABA concentration - response curve for human alpha1beta3gamma2 GABAARs expressed
      in Xenopus oocytes, and enhancing [3H]muscimol binding to alpha1beta3gamma2
      GABAARs expressed in HEK293 cells. With EC50 of 110 nM, 11-AziAP is one the most
      potent general anesthetics reported. [3H]F4N3Bzoxy-AP and [3H]11-AziAP, at
      anesthetic concentrations, photoincorporated into alpha- and beta-subunits of
      purified alpha1beta3gamma2 GABAARs, but labeling at the subunit level was not
      inhibited by alphaxalone (30 MUM). The enhancement of photolabeling by 3H
      azietomidate and 3H-mTFD-MPAB in the presence of either of the two steroid
      photoprobes indicates the neurosteroid binding site is different from, but
      allosterically related to, the etomidate and barbiturate sites. Our observations
      are consistent with two hypotheses. First, F4N3Bzoxy-AP and 11-aziAP bind to a
      high affinity site in such a pose that the 11-photoactivatable moiety, that is
      rigidly attached to the steroid backbone, points away from the protein. Second,
      F4N3Bzoxy-AP, 11-aziAP and other steroid anesthetics, which are present at very
      high concentration at the lipid-protein interface due to their high
      lipophilicity, act via low affinity sites, as proposed by Akk et al.
      (Psychoneuroendocrinology2009, 34S1, S59-S66).

PMID- 28505539
TI  - Revisiting bilateral thalamotomy for tremor.
AB  - MRI guided focused ultrasound surgery (MRgFUS) has been FDA approved for
      unilateral treatment of essential tremor (ET). Before this non-incisional
      lesioning method can be applied to the treatment of both hemispheres the previous
      experience with bilateral thalamic ablation must be addressed. In particular, the
      high incidence of worsening of speech and balance associated with bilateral
      surgical thalamotomy, a rationale for the development of deep brain stimulation.
      The highest incidence of these complication occurred in the early years of
      surgery for movement disorders, when neither MRI nor current stereotactic methods
      were available. The vast majority of these initial patients suffering these
      complications had Parkinson's disease where approximately 30% developed worsening
      dysarthria and ataxia after bilateral thalamotomy. Patients suffering these
      complications commonly had baseline abnormalities in speech and balance or
      worsening symptoms after a first unilateral procedure. The more contemporary
      experience with bilateral thalamotomy in the ET population is both much more
      limited in patient numbers (includes patients after Gamma Knife radiosurgery),
      and shows a much lower rate of these complications (approximately 5%). This more
      recent experience suggests that bilateral thalamotomy using closed incisionless
      methods such as MRgFUS has the potential to safely improve ET patients with axial
      or bilateral limb involvement, if done in a staged manner excluding patients with
      baseline dysarthria or ataxia or transient worsening of these symptoms following
      a unilateral procedure.

PMID- 28505540
TI  - Salivary protective factors in patients suffering from decompensated type 2
      diabetes.
AB  - PURPOSE: Defining the level of protective factors in saliva of patients suffering
      from decompensated type 2 diabetes. MATERIAL AND METHODS: 50 Patients with
      diagnosis of decompensated type 2 diabetes, including 32 women and 18 men at the
      age of 57.9+/-9.2 years. The control group consisted of 50 people among whom
      there were 38 women and 12 men whose average age was estimated at 51.2+/-9.9
      years. RESULTS: It was stated the increased concentration of total protein by 60%
      and decreased concentration of IgA by 70%, of lysozyme by 27% and of lactoferrin
      by 40% in resting saliva of patients with type 2 diabetes if compared to the
      control group. These outcomes were really statistically meaningful. The
      evaluation of dependences between the analyzed protective factors and the
      indicator of oral cavity condition proved the positive correlation between the
      concentration of total protein and the number of DMFT (i.e. the rate of caries
      intensity). The remaining coefficients of correlation being evaluated proved to
      be negative and statistically meaningless. CONCLUSION: The obtained outcomes
      prove a high influence of proteins included in saliva on the prevalence and
      development of caries at patients with decompensated type 2 diabetes.

PMID- 28505541
TI  - Retirement blues.
AB  - This paper analyses the short- and longer-term effects of retirement on mental
      health in ten European countries. It exploits thresholds created by state pension
      ages in an individual-fixed effects instrumental-variable set-up, borrowing
      intuitions from the regression-discontinuity design literature, to deal with
      endogeneity in retirement behaviour. The results display no short-term effects of
      retirement on mental health, but a large negative longer-term impact. This impact
      survives a battery of robustness tests, and applies to women and men as well as
      people of different educational and occupational backgrounds similarly. Overall,
      the findings suggest that reforms inducing people to postpone retirement are not
      only important for making pension systems solvent, but with time could also pay a
      mental health dividend among the elderly and reduce public health care costs.

PMID- 28505542
TI  - Computational modeling of protein assemblies.
AB  - Computational methods to predict the 3D structures of protein interactions fall
      into 3 categories-template based modeling, protein-protein docking and
      hybrid/integrative modeling. The two most important considerations for modeling
      methods are sampling and scoring conformations. Sampling has benefitted from
      techniques such as fast Fourier transforms (FFT), spherical harmonics and higher
      order manifolds. Scoring complexes to determine binding free energy is still a
      challenging problem. Rapid advances have been made in hybrid modeling where
      experimental data are amalgamated with computations. These methods have received
      a boost from the popularity of experimental methods such as electron microscopy
      (EM). While increasingly larger and complicated complexes are now getting
      elucidated by integrative methods, modeling conformational flexibility remains a
      challenge. Ongoing improvements to these techniques portend a future where
      organelles or even cells could be accurately modeled at a molecular level.

PMID- 28505543
TI  - Chronic administration of apple polyphenols ameliorates hyperglycaemia in high
      normal and borderline subjects: A randomised, placebo-controlled trial.
AB  - AIMS: We previously reported that apple polyphenols (AP) and their major active
      components, procyanidins, had beneficial effects on glucose homeostasis and
      diabetes in diabetic ob/ob mice. The present study was performed to evaluate the
      effects of chronic AP administration on glucose tolerance in high-normal and
      borderline human subjects. METHODS: Subjects (n=65) with a fasting plasma glucose
      (FPG) level of 100-125mg/dL determined during a recent health check-up were
      randomised to receive tablets containing AP (600mg/day) or placebo tablets for
      12weeks in a double-blinded, placebo-controlled clinical trial. The primary
      outcome was insulin resistance, assessed using a 75g oral glucose tolerance test
      (OGTT). RESULTS: The 12-week chronic administration of AP significantly reduced
      the increase in glucose at 30-min post-75g OGTT (OGTT30-min glucose) value,
      compared to the placebo regimen. Furthermore, in a subgroup of the high-normal
      (FPG value, 100-109mg/dL; 2-h post-75g OGTT glucose (OGTT2-h glucose) value,
      <140mg/dL) and borderline (FPG value, 110-125mg/dL; OGTT2-h glucose value,
      <140mg/dL and FPG value, <126mg/dL; OGTT2-h glucose value, 140-199mg/dL)
      subjects, OGTT30-min glucose value in the AP group (164.0+/-7.4mg/dL) was
      significantly lower than that of the placebo group (194.7+/-10.4mg/dL, p<0.05).
      No significant changes in the other lipid parameters and cytokine levels were
      observed. CONCLUSIONS: Chronic AP administration significantly improved impaired
      glucose tolerance in high-normal and borderline subjects. Larger and/or longer
      term scale human studies are required to confirm the potential glucose
      homeostasis of AP.

PMID- 28505544
TI  - Real-life experience of patients starting insulin degludec. A multicenter
      analysis of 1064 subjects from the German/Austrian DPV registry.
AB  - BACKGROUND: The long-acting insulin analogue degludec is a therapeutic option for
      patients with type 1 (T1D) or type 2 diabetes (T2D). Aim of this analysis was to
      investigate differences in clinical characteristics of patients before and after
      initiating degludec use in a cohort of German/Austrian patients. METHODS: 1064
      subjects with T1D/T2D and documented degludec use from the Diabetes-Patient
      Follow-Up (DPV) registry were included. The follow-up cohort (n=421) comprised
      patients with available data before and 3-15months after switching to degludec. A
      t-test for paired values was implemented to compare rates of severe
      hypoglycaemia, and mean values for HbA1C, BMI, basal insulin dose/kg
      bodyweight/day, and the number of basal insulin injections/day before and after
      switching to degludec Results were stratified by type of diabetes. In T1D,
      subgroup analyses were conducted (age, sex, basal insulin used before switching).
      P<0.05 was considered significant. FINDINGS: In T1D (n=360), basal insulin dose
      (0.43+/-0.17 to 0.38+/-0.13IU) and the number of basal injections/day (1.7+/-0.6
      to 1.1+/-0.3) decreased whereas BMI increased from 23.2+/-4.8 to 24.0+/-5.0kg/m2
      (all p<0.0001) after switching to degludec. No significant changes were observed
      regarding rates of severe hypoglycaemia or HbA1C-values. Findings were comparable
      for subgroups. In T2D (n=61), basal insulin dose (0.41+/-0.23 to 0.38+/-0.21;
      p=0.1730) and the number of basal injections/day (1.3+/-0.4 to 1.1+/-0.3;
      p=0.0097) decreased after switching to degludec. HbA1C improved from 7.9+/-1.6 to
      7.1+/-1.5% (p<0.0001). CONCLUSIONS: The DPV registry provides data from real-life
      diabetes care. Our analysis predominantly confirmed results from clinical trials
      and provides additional information complementing the clinical study program of
      degludec.

PMID- 28505545
TI  - Leg stiffness during sprinting in transfemoral amputees with running-specific
      prosthesis.
AB  - Carbon fiber running-specific prostheses are designed to reproduce the spring
      like stepping behavior of individuals similar to springs loaded by the entire
      body mass (i.e. spring-mass model). The aim of this study was to test whether leg
      stiffness would be modulated differently between intact and prosthetic legs in
      transfemoral amputees wearing RSP during sprinting. Eight unilateral transfemoral
      amputees performed maximum sprinting along an indoor overground runway. Leg
      stiffness was calculated from kinetic and kinematic data in intact and prosthetic
      legs. The results showed that leg stiffness was for the prosthetic limb
      approximately 12% decreased compared to the intact limb. Although there was no
      difference in leg compression between the legs, maximal vertical ground reaction
      force was significantly greater in the intact leg than in the prosthetic one.
      These results indicate that asymmetric modulation of leg stiffness in
      transfemoral amputees with running-specific prostheses is mainly associated with
      asymmetric ground reaction force.

PMID- 28505546
TI  - Quantifying sources of variability in gait analysis.
AB  - Measurements from gait analysis are affected by many sources of variability.
      Schwartz et al. [1] illustrated an experimental design and methods to estimate
      these variance components. However, the derivation contains errors which could
      severely bias the estimation of some components. Therefore, in this paper, we
      presented correction to this method using ANOVA and Likelihood methods.
      Furthermore, we demonstrated how commonly used reliability indices like CMC and
      ICC may be derived from the variance components. We advocate the use of the
      variance components, in preference to reliability indices, because the variance
      components are easier to interpret, with understandable units.

PMID- 28505547
TI  - Synthesis of indole analogs as potent beta-glucuronidase inhibitors.
AB  - Natural products are the main source of motivation to design and synthesize new
      molecules for drug development. Designing new molecules against beta
      glucuronidase inhibitory is utmost essential. In this study indole analogs (1-35)
      were synthesized, characterized using various spectroscopic techniques including
      1H NMR and EI-MS and evaluated for their beta-glucuronidase inhibitory activity.
      Most compounds were identified as potent inhibitors for the enzyme with IC50
      values ranging between 0.50 and 53.40MUM, with reference to standard d-saccharic
      acid 1,4-lactone (IC50=48.4+/-1.25MUM). Structure-activity relationship had been
      also established. The results obtained from docking studies for the most active
      compound 10 showed that hydrogen bond donor features as well as hydrogen bonding
      with (Oepsilon1) of nucleophilic residue Glu540 is believed to be the most
      importance interaction in the inhibition activity. It was also observed that
      hydroxyl at fourth position of benzylidene ring acts as a hydrogen bond donor and
      interacts with hydroxyl (OH) on the side chain of catalysis residue Tyr508. The
      enzyme-ligand complexed were being stabilized through electrostatic pi-anion
      interaction with acid-base catalyst Glu451 (3.96A) and thus preventing Glu451
      from functioning as proton donor residue.

PMID- 28505548
TI  - Enzymatic synthesis and semi-preparative isolation of N-acetylmuramic acid 6
      phosphate.
AB  - N-acetylmuramic acid 6-phosphate (MurNAc-6P) is a constituent of the bacterial
      peptidoglycan cell wall, serving as an anchor point of secondary cell wall
      polymers such as teichoic acids, and it is a key metabolite of the peptidoglycan
      recycling metabolism. Thus, there is a demand for MurNAc-6P as a standard for
      cell wall compositional and metabolic analyses and, in addition, as a substrate
      for peptidoglycan recycling enzymes, e.g. MurNAc-6P etherases (MurQ) and MurNAc
      6P phosphatases (MupP), or as an effector molecule of transcriptional MurR
      regulators. However, MurNAc-6P is commercially not available. We report here the
      facile enzymatic production of MurNAc-6P in mg-scale from MurNAc and ATP,
      applying Clostridium acetobutylicum kinase MurK, and purification by semi
      preparative HPLC. MurNAc-6P was quantified using a coupled enzyme assay,
      revealing 75-80% overall product yield, and high purity was confirmed by mass
      spectrometry and proton NMR.

PMID- 28505549
TI  - Intramammary inoculation of Panax ginseng plays an immunoprotective role in
      Staphylococcus aureus infection in a murine model.
AB  - The immunoprotective effect of Panax ginseng (Pg) extract was investigated in a
      mouse mastitis model. Lactating female mice were intramammarily inoculated with
      Pg or placebo, and then were challenged with S. aureus, while other group was
      inoculated with S. aureus alone. The number of bacteria recovered from mammary
      glands was significantly lower in Pg-treated S. aureus-infected mice (group I)
      compared with placebo-treated S. aureus-infected mice (group II) and S. aureus
      infected mice (group III). The mRNA expression of TLR2, TLR4, IL-1alpha and TNF
      alpha was influenced by treatment; being the transcript levels for all genes
      higher in group I compared with group II and III. Activation of NF-kappaB and the
      number of monocytes-macrophages in mammary gland tissue was significantly
      increased in group I compared with group II and III. Pg extract was able to
      trigger an adequate immune response to confront an infection demonstrating its
      protective effect and potential for preventing bovine intramammary infections.

PMID- 28505550
TI  - Histological differences in the adrenal glands and cortisol levels of suckling
      dairy goat kids in enriched and non-enriched environments.
AB  - Intensive production systems can negatively affect the welfare of goats.
      Environmental enrichment techniques can be used to reduce stress. The aim of this
      study was analyze the effect of environmental enrichment on the histological
      characteristics of adrenal glands, cortisol levels and weekly weight gain of
      suckling Alpine French male kids under confinement. A randomised design was used
      to test the effect of the treatment. The animals (n=20) were randomly assigned to
      two treatments (enriched and non-enriched) with two replicates each. Enrichment
      elements included elevated sacks of henequen, trunks, tires and coconuts. The
      cortisol levels were measured weekly. Male kids were euthanized when their weight
      reached 10kg, and immediately after euthanasia, samples of the adrenal glands
      were collected. The adrenal glands were weighed and measured, and histological
      sections were taken and fixed. Four hundred cells were measured from each animal,
      with two blind measurements taken from each sample. There were no significant
      differences between experimental groups (P>0.05) in the weigh, size, the area of
      cells from the glomerulosa and fasciculata areas of the adrenal glands, the
      cortisol levels and weekly weight gain. However, there were histological
      differences between the glomerular and fascicular zones of the left and right
      adrenal glands of the different groups (P<0.05). These findings suggest that
      adrenal glands of animals in non-enriched environment, contained histological
      changes, suggestive of increased activity. We suggest testing adrenal histology
      as an indicator of stress and recommend the use of environmental enrichment as a
      means to reduce stress.

PMID- 28505551
TI  - The "80 Joule criterion" reconsidered today.
AB  - The 80 Joule or 58 ft-lb injury criterion first mentioned by Rohne was read in
      his textbook and analyzed in detail. Additional review of early literature to
      this topic was performed. Neither Rohne nor ballisticians ten years later gave an
      indication how the 8mkg value validates immobilization and how immobilization was
      defined. The penetration performance of the bullet M/88 was successfully
      demonstrated in the 80 Joule status when fired in the 100m/s domain from the
      Gewehr 88. The bullets were fired into ballistic soap under laboratory firing
      conditions of today. The evaluation of measured velocities, depth of penetration
      and the recording with high speed camera and CT scan was performed. An acceptable
      correlation was found between the kinetic energy deposited and the penetration
      depth. The soap penetration in the 80 Joule status is surprisingly high and
      substantiates Rohne's allegation of a human's immobilization from the
      battlefield. A validation of the criterion was not possible and it is recommended
      not to use an energy limit value to define any sort of incapacitation.

PMID- 28505552
TI  - Probabilistic pharmacokinetic models of decompression sickness in humans, part 1:
      Coupled perfusion-limited compartments.
AB  - Decompression sickness (DCS) is a disease caused by gas bubbles forming in body
      tissues following a reduction in ambient pressure, such as occurs in scuba
      diving. Probabilistic models for quantifying the risk of DCS are typically
      composed of a collection of independent, perfusion-limited theoretical tissue
      compartments which describe gas content or bubble volume within these
      compartments. It has been previously shown that 'pharmacokinetic' gas content
      models, with compartments coupled in series, show promise as predictors of the
      incidence of DCS. The mechanism of coupling can be through perfusion or
      diffusion. This work examines the application of five novel pharmacokinetic
      structures with compartments coupled by perfusion to the prediction of the
      probability and time of onset of DCS in humans. We optimize these models against
      a training set of human dive trial data consisting of 4335 exposures with 223 DCS
      cases. Further, we examine the extrapolation quality of the models on an
      additional set of human dive trial data consisting of 3140 exposures with 147 DCS
      cases. We find that pharmacokinetic models describe the incidence of DCS for
      single air bounce dives better than a single-compartment, perfusion-limited
      model. We further find the U.S. Navy LEM-NMRI98 is a better predictor of DCS risk
      for the entire training set than any of our pharmacokinetic models. However, one
      of the pharmacokinetic models we consider, the CS2T3 model, is a better predictor
      of DCS risk for single air bounce dives and oxygen decompression dives.
      Additionally, we find that LEM-NMRI98 outperforms CS2T3 on the extrapolation
      data.

PMID- 28505553
TI  - Linking eating and weight control attitudes to relationship experiences: A large
      scale survey of adolescent females.
AB  - OBJECTIVE: To examine the extent to which family conflict, peer bullying and
      psychological distress account for eating and weight loss attitudes in adolescent
      females. This study examined the degree to which psychological distress mediated
      the association between family conflict and eating and weight loss attitudes, and
      the association of bullying and eating and weight loss attitudes. METHOD: Females
      aged between 11 and 17 years (N = 5125) were recruited from schools in the State
      of Victoria (Australia). Key measures included psychological distress, family
      conflict, and bullying victimisation. RESULTS: A structural model showed good
      fit, and all predictors were significant. Psychological distress mediated the
      association between eating and weight loss attitudes, and family problems and
      bullying. CONCLUSION: Family conflict and peer bullying were associated with
      eating and weight loss attitudes and this association may occur via psychological
      distress. Early intervention programs may benefit from a focus on family and peer
      relationships.

PMID- 28505555
TI  - Postcard Pick-me-up: The power of simple acts of kindness.

PMID- 28505554
TI  - A mixed-method evaluation of a New Zealand based midwifery education development
      unit.
AB  - The Midwifery Development Education Service was established in the Birthing Unit
      at Middlemore Hospital in South Auckland New Zealand in 2007. The service is
      unique in the New Zealand midwifery context for the way it operates as a
      collaboration between the education and health provider to optimise the clinical
      learning experience of student midwives. This paper reports on the evaluation of
      the Midwifery Development Education Service that was undertaken in 2015. The
      evaluation captured the views and experience of students and midwives who had
      been involved with, or had worked alongside, the service. A mixed-method approach
      was adopted for the evaluation study, comprising of an anonymous on-line survey,
      qualitative interviews and focus group discussion. Considerable satisfaction with
      the service was identified. This article draws attention to participants'
      perceptions of the service as supporting student midwives; the significance of
      quality time in the provision of the clinical midwifery education; the situating
      of the service at a unique vantage point (overseeing the needs of the university
      and the hospital) and its impact upon the learning culture of education within
      the unit. A potential tension is also identified between the provision of a
      supportive learning environment and the assessment of student performance.

PMID- 28505556
TI  - Building midwifery educator capacity using international partnerships: Findings
      from a qualitative study.
AB  - Midwifery educators play a critical role in strengthening the midwifery workforce
      globally, including in low and lower-middle income countries (LMIC) to ensure
      that midwives are adequately prepared to deliver quality midwifery care. The most
      effective approach to building midwifery educator capacity is not always clear.
      The aim of this study was to determine how one capacity building approach in
      Papua New Guinea (PNG) used international partnerships to improve teaching and
      learning. A qualitative exploratory case study design was used to explore the
      perspectives of 26 midwifery educators working in midwifery education
      institutions in PNG. Seven themes were identified which provide insights into the
      factors that enable and constrain midwifery educator capacity building. The study
      provides insights into strategies which may aid institutions and individuals
      better plan and implement international midwifery partnerships to strengthen
      context-specific knowledge and skills in teaching. Further research is necessary
      to assess how these findings can be transferred to other contexts.

PMID- 28505557
TI  - Follow-up of patients with localized breast cancer and first indicators of
      advanced breast cancer recurrence: A retrospective study.
AB  - We conducted a retrospective study to assess the follow-up of patients with
      localized breast cancer and the first indicators of advanced breast cancer
      recurrence. All patients with advanced breast cancer recurrence treated between
      January 2010 and June 2016 in our institution were registered. Among these
      patients, 303 patients initially treated for early breast cancer with curative
      intent were identified. After initial curative treatment, follow-up involved the
      oncologist, the general practitioner and the gynecologist in 68.0%, 48.9% and
      19.1% of cases, respectively. The median DFI was 4 years for luminal A, 3.8 years
      for luminal B, 3.7 years for HER2-positive and 1.5 years for TNBC (p = 0.07).
      Breast cancer tumor marker was prescribed for 164 patients (54.1%). No difference
      in terms of follow-up was observed according to the molecular subtype. Symptoms
      were the primary indicator of relapse for 143 patients (47.2%). Breast cancer
      recurrence was discovered by CA 15.3 elevation in 57 patients (18.8%) and by CAE
      elevation in 3 patients (1%). The rate of relapse diagnosed by elevation of CA
      15.3 or CAE was not statistically associated with the molecular subtype (p =
      0.65). Luminal A cases showed a significantly higher rate of bone metastases (p =
      0.0003). TNBC cases showed a significantly higher rate of local recurrence (p =
      0.002) and a borderline statistical significant higher rate of lung/pleural
      metastases (p = 0.07). Follow-up recommendations could be adapted in clinical
      practice according to the molecular subtype. General practitioners should be more
      involved by the specialists in breast cancer follow-up.

PMID- 28505558
TI  - Oncoplastic techniques: Attitudes and changing practice amongst breast and
      plastic surgeons in Great Britain.
AB  - PURPOSE: The availability, acceptability and practice of oncoplastic surgery has
      increased over the last 5 years. This study aims to describe how the breast and
      plastic surgical workforce has adapted to provide oncoplastic breast surgery.
      METHODS: A questionnaire was distributed to members of the Association of Breast
      Surgery and BAPRAS, and results compared to a survey completed in 2010. RESULTS:
      In 2010, 228 respondents completed the survey compared to 237 in 2015, of whom
      204 were consultants (105 General or Breast Surgeons and 99 Plastic Surgeons).
      The range of procedures performed by Plastic Surgeons has remained static, the
      General and Breast Surgeons are performing proportionally more therapeutic
      mammaplasty (p < 0.001), breast reduction/mastopexy, and latissimus dorsi
      reconstructions. In 2015, surgeons are less concerned about the risks of
      lipomodelling than in 2010, with an increase the proportion of breast (55% vs.
      26%) and plastic (91% vs. 58%) surgeons performing the technique. DISCUSSION:
      Specific concerns about oncoplastic surgery have decreased over the last five
      years, with a greater proportion of surgeons performing oncoplastic surgery
      including lipomodelling. The majority of breast surgeons in 2015 remain
      interested in further training in oncoplastic techniques (75%) but over the last
      5 years, plastic surgeons interest in further training in oncoplastic surgery has
      dropped from 62% to 27%. About half of all breast and plastic surgeons felt that
      oncoplastic surgery should be available for all women and oncological and wound
      healing concerns had significantly reduced between 2010 and 2015 (p < 0.05).

PMID- 28505559
TI  - A two phased study on health care professionals' perceptions of single or multi
      use of intermittent catheters.
AB  - AIMS: This two phase study aimed to explore health care professionals' teaching
      and prescribing practice related to intermittent catheterisation and to identify
      their perceptions about the possible implementation of a mixed (single and multi
      use) package for intermittent catheterization. INTRODUCTION: Single-use
      intermittent catheters are the norm in the UK although multi-use is common in
      some other countries. A recent Cochrane review found no difference in
      complications, including urinary tract infection rates, between those using
      single or multi-use catheters. A flexible option of both multi-use and single use
      intermittent catheters could provide users with more flexible choices in self
      care. However, understanding health care professionals' perspectives is one of
      the keys to developing a multi-use intervention. DESIGN: A qualitative research
      framework using in-depth interviews to inform an on line survey. METHOD: In-depth
      interviews were conducted with health care professionals based in the UK who
      prescribe catheters, teach intermittent catheterisation or manage an intermittent
      catheterisation service. The interviewees were selected to represent a range of
      clinical areas, experience and professions - continence advisors, urology,
      multiple sclerosis (MS) and spinal cord injury specialist nurses, and General
      Practitioners. Following framework analysis the themes and factors identified
      were used to develop an on-line survey which was disseminated through health care
      professional networks whose members saw patients who use intermittent catheters.
      RESULTS: Nineteen health care professionals participated in the telephone
      interviews; 206 completed the survey. A wide range of professionals in terms of
      experience and specialty afforded rich information regarding the contextual
      issues around the teaching and prescribing of intermittent catheters. The primary
      finding was that health care professionals were concerned about 'minimising
      health risk' and maximising 'normalcy' for those using intermittent self
      catheterisation. Health care professionals who worked in the acute setting or had
      no experience of re-use were most resistant to the re-use of catheters.
      Professionals requested evidence that a multi-use package would not increase the
      risk of developing a urinary tract infection or increase the burden of use to a
      patient before a mixed package would be considered. CONCLUSIONS: For multi-use to
      be acceptable, evidence based guidelines must be available for healthcare
      professionals and cleaning methods must be acceptable and safe for intermittent
      catheter users. Further evidence may be required to establish that a mixed
      catheter package is equivalent to single use only, particularly for outcomes such
      as urinary tract infection, urethral injury and quality of life. RELEVANCE TO
      CLINICAL PRACTICE: This paper highlights that if multi-use catheters are to be
      successfully introduced into clinical practice, the ease of use, safety and
      effectiveness of the cleaning technique will need to be convincingly demonstrated
      by a range of well-defined users.

PMID- 28505560
TI  - Integrated signal probe based aptasensor for dual-analyte detection.
AB  - For the multi-analyte detection, although the sensitivity has commonly met the
      practical requirements, the reliability, reproducibility and stability need to be
      further improved. In this work, two different aptamer probes labeled with redox
      tags were used as signal probe1 (sP1) and signal probe2 (sP2), which were
      integrated into one unity DNA architecture to develop the integrated signal probe
      (ISP). Comparing with the conventional independent signal probes for the
      simultaneous multi-analyte detection, the proposed ISP was more reproducible and
      accurate. This can be due to that ISP in one DNA structure can ensure the
      completely same modification condition and an equal stoichiometric ratio between
      sP1 and sP2, and furthermore the cross interference between sP1 and sP2 can be
      successfully prevented by regulating the complementary position of sP1 and sP2.
      The ISP-based assay system would be a great progress for the dual-analyte
      detection. Combining with gold nanoparticles (AuNPs) signal amplification, the
      ISP/AuNPs-based aptasensor for the sensitive dual-analyte detection was explored.
      Based on DNA structural switching induced by targets binding to aptamer, the
      simultaneous dual-analyte detection was simply achieved by monitoring the
      electrochemical responses of methylene blue (MB) and ferrocene (Fc) This proposed
      detection system possesses such advantages as simplicity in design, easy
      operation, good reproducibility and accuracy, high sensitivity and selectivity,
      which indicates the excellent application of this aptasensor in the field of
      clinical diagnosis or other molecular sensors.

PMID- 28505561
TI  - Class enzyme-based motors for "on the fly" enantiomer analysis of amino acids.
AB  - Here, two class-enzyme motors are properly designed allowing the rapid dispersion
      of the class-enzyme D-amino acid oxidase (DAO) and L-amino acid oxidase (LAO) for
      selective "on the fly" biodetection of D and L-amino acids (AAs), respectively.
      The efficient movement together with the continuous release of fresh class-enzyme
      leads to a greatly accelerated enzymatic reaction processes without the need of
      external stirring or chemical and physical attachment of the enzyme. Ultra-fast
      detection (<2min) and accurate quantifications of L-phenylalanine (L-Phe) in
      plasma and whole-blood newborns samples diagnosed with Phenylketonuria and total
      D-AAs in Vibrio cholera cultures are pioneer illustrated as relevant examples of
      each enantiomer determination. These results opens clearly novel avenues in
      biosensing for fast screening diagnostics, decentralized monitoring and design of
      future points of care.

PMID- 28505562
TI  - Ultra-fast electronic detection of antimicrobial resistance genes using
      isothermal amplification and Thin Film Transistor sensors.
AB  - A low cost thin-film transistor (TFT) nanoribbon (NR) sensor has been developed
      for rapid real-time detection of DNA amplification using an isothermal
      Recombinase Polymerase Amplification (RPA) method. The semiconductor chip
      measures DNA amplification through a pH change, rather than via fluorescence. The
      utility of the method was demonstrated by amplifying CTX-M and NDM, two genes
      that confer bacterial resistance to cephalosporins and carbapenems, respectively.
      It is shown that this approach provides extremely fast and sensitive detection.
      It can detect <10 copies of the gene in genomic DNA extracted from E. coli or K.
      pneumoniae clinical isolates within a few minutes. A differential readout system
      was developed to minimize the effect of primer-dimer amplification on the assay.
      The simple device has the potential for low cost, portable and real-time nucleic
      acid analysis as a Point of Care device.

PMID- 28505564
TI  - Niches after cesarean section in a population seeking hysteroscopic
      sterilization.
AB  - OBJECTIVE: To study the prevalence of hysteroscopically evaluated disruptions of
      the integrity of the uterine wall ('niches') in women with and without a previous
      cesarean section. STUDY DESIGN: A prospective cohort study was performed in a
      teaching hospital in the Netherlands. Women seeking hysteroscopic sterilization
      were included. A hysteroscopic evaluation of the anterior wall of the uterus and
      cervix to identify the existence of disruptions (niches) was performed in a
      standard manner. Primary outcome was the presence of a uterine niche, defined as
      any visible defect, disruption, or concavity (gap) in the anterior wall.
      Secondary outcome was to develop a registration form of niche features for
      hysteroscopic evaluation. RESULTS: In total, 713 women were included, 603 without
      and 110 with a previous cesarean section. In women with a previous cesarean
      Section 83 (75%) niches were observed using hysteroscopy. Anterior wall
      disruptions were not observed in women without a cesarean section. The following
      niche features were identified and incorporated in a registration form: polyps,
      cysts, myometrium defect, fibrotic tissue, (abnormal) vascular pattern, lateral
      branches, mucus production inside the defect, and bleeding. CONCLUSION: In a
      prospective cohort study among women undergoing hysteroscopic sterilization, a
      uterine niche could be detected by hysteroscopy in 75% of women with a previous
      cesarean section.

PMID- 28505563
TI  - Ultrasensitive magnetic field-assisted surface plasmon resonance immunoassay for
      human cardiac troponin I.
AB  - An ultrasensitive surface plasmon resonance (SPR) immunoassay was developed for
      the specific detection of human cardiac troponin I (cTnI), a principle diagnostic
      marker for myocardial damage. The thin gold film evaporated on a glass slate,
      which was employed as the SPR sensing film, was modified by hollow gold
      nanoparticles (HGNPs) and polydopamine (PDA) sequentially, and then was
      immobilized with antibodies for specific recognition of target analyte.
      Electronic coupling of the surface plasmon waves originating from the HGNPs and
      the gold film leads to the remarkable amplification of SPR response. The PDA film
      modified on the gold film via self-polymerization of dopamine (DA) facilitates
      the direct immobilization of capture antibodies (cAb). To separate and enrich the
      target analyte, PDA-wrapped magnetic multi-walled carbon nanotubes (MMWCNTs-PDA)
      were conjugated with detection antibodies (dAb) and used as the extracting agent
      for the magnetic extraction of cTnI in sample. Large surface area of MMWCNTs-PDA
      ensures its loading capacity for dAb, as well as its extraction efficiency for
      cTnI. By serving as the "vehicles" for fast delivering the concentrated analyte
      to the SPR sensing surface, MMWCNTs-PDA-dAb also overcomes the disadvantage of
      slow diffusion-limited mass transfer and matrix interference effect in regular
      patterns. The combination of the above improvements results in the significant
      sensitivity enhancement of the SPR immunoassay. The concentration of cTnI with
      minimum detectable SPR response obtained by the present assay is 1.25ngmL-1,
      which is 1000-fold lower than that obtained by the traditional SPR immunoassay
      based on PDA-modified gold film.

PMID- 28505565
TI  - DFT and TD-DFT theoretical studies on photo-induced electron transfer process on
      [Cefamandole].C60 nano-complex.
AB  - The C60 fullerene displays a considerable electronegativity. It has a unique
      photophysical and electrochemical behavior that can be used as a suitable drug
      carrier. In the present study, the interaction of C60 fullerene as an electron
      recipient with the Cefamandole antibiotic was investigated in both ground and
      excited states using DFT and TD-DFT methods. The study of the interaction of C60
      and Cefamandole via electron localization function (ELF) and reduced density
      gradient (RDG) revealed that the complex formation is of van der Waals type. The
      data from natural bonding orbitals (NBO) analysis also confirmed the interaction
      type. The study of absorption and emission spectrum via CAM-B3LYP in the TD-SCF
      state showed that the emission peak of C60 fullerene in the 591.73nm after the
      complex formation results in the extinction of this emission spectrum due to
      charge transfer (CT) from chelator to fluorophore. The photoinduced electron
      transfer (PET) process was investigated using the electron hole theory.

PMID- 28505567
TI  - One-step versus two-step mechanism of Diels-Alder reaction of 1-chloro-1
      nitroethene with cyclopentadiene and furan.
AB  - DFT computational study shows that Diels-Alder (DA) reactions of 1-chloro-1
      nitroethene with cyclopentadiene and furan have polar nature. However, their
      mechanism is substantially different. In particular, 1-chloro-1-nitroethene react
      with cyclopentadiene according to one-step mechanism. In the same time, more
      favourable channel associated with the P-DA reaction between furan and 1-chloro-1
      nitroethene is a domino process, that comprises an initial hetero-Diels-Alder
      reaction yielding a [2+4] cycloadduct, which experiences a subsequent [3,3]
      sigmatropic shift to yield the expected formal [4+2] cycloadduct. This is a
      consequence of more polar nature of reaction, due to higher nucleophilicity of
      furan in comparison to cyclopentadiene.

PMID- 28505566
TI  - Conformational Study of the Structure of dibenzo-18-crown-6. Comparison with 18
      crown-6.
AB  - We report for the first time the conformational analysis of dibenzo-18-crown-6,
      db18c6. The conformational search was carried out using the CONFLEX
      conformational search method of cyclic molecules. Energies were calculated for
      the low-lying predicted conformations at different levels of theory up to the
      G3MP2 level. At the G3MP2 level, the predicted ground state (GS) conformation was
      more stable than the experimental conformation by only 1.60kcal/mol. Strong
      similarity was found between the GS structure and experimental conformations of
      db18c6 and 18-crown-6, 18c6. The GS and experimental conformations of db18c6 are
      non-planar. This allows db18c6 to exist in optically active enantiomers. Similar
      to 18c6, it was concluded that the db18c6 structure is stabilized by
      intramolecular hydrogen bond. We also performed the computations for the water
      and chloroform solution phase, where the same conformation was predicted as the
      GS conformation.

PMID- 28505568
TI  - The structural relationship between early nutrition, cognitive skills and non
      cognitive skills in four developing countries.
AB  - This study provides evidence about how cognitive and non-cognitive skills are
      acquired during childhood in four developing countries (Ethiopia, India, Peru and
      Vietnam), highlighting the role of early nutrition as a determinant in this
      process. An increase of one standard deviation in height-for-age at the age of 1
      is found to have a total effect on cognitive skills at age 8 by 5.4 percent in
      Ethiopia, 9.0 percent in India, 7.6 percent in Peru and 8.4 percent in Vietnam.
      The corresponding total effect on non-cognitive skills is 1.1 percent in
      Ethiopia, 3.4 percent in India, 2.6 percent in Peru and 1.7 percent in Vietnam.
      The evidence suggests the effect of early nutrition on non-cognitive skills is
      indirect, mediated by cognitive skills. The effect is also relatively small in
      magnitude.

PMID- 28505569
TI  - Comparison of the Hologic Aptima HIV-1 Quant Dx Assay to the Roche COBAS
      Ampliprep/COBAS TaqMan HIV-1 Test v2.0 for the quantification of HIV-1 RNA in
      plasma samples.
AB  - BACKGROUND: HIV-RNA is the most important parameter for monitoring antiviral
      treatment in individuals infected with HIV-1. Knowledge of the performance of
      different tests for the quantification of HIV-1 RNA is therefore important for
      clinical care. OBJECTIVES: To compare the analytical performance of the Aptima
      HIV-1 Quant Dx Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HIV-1 Test
      v2.0 (CAPCTMv2) for the quantification of HIV-1 RNA in plasma samples. STUDY
      DESIGN: The performance of the two tests was compared on 216 clinical plasma
      samples, on dilutions series in seven replicates of five clinical samples of
      known subtype and on ten replicates of the Acrometrix High and Low Positive
      Control. RESULTS: Bland-Altman analysis of 130 samples that quantified in both
      tests did not show indications of gross mis-quantification of either test. A
      tendency of the Aptima assay to quantify higher at high viral load compared to
      the CAPCTMv2 was observed in Bland-Altman analysis, by Deming regression (Slope
      1.13) and in dilution series of clinical samples. Precision evaluated using the
      Acrometrix Positive Controls was similar for the High Control (CV: 1.2% vs. 1.3%;
      Aptima assay vs. CAPCTMv2 test, respectively), but differed for the Low control
      (CV: 17.9% vs. 7.1%; Aptima assay vs. CAPCTMv2 test, respectively). However, this
      did not impact clinical categorization of clinical samples at neither the 50
      cp/mL nor 200 cp/mL level. CONCLUSION: The Aptima assay and the CAPCTMv2 test are
      highly correlated and are useful for monitoring HIV-infected individuals.

PMID- 28505570
TI  - Clinical evaluation of the BioFire FilmArray(r) BioThreat-E test for the
      diagnosis of Ebola Virus Disease in Guinea.
AB  - BACKGROUND: The recent West Africa Ebola outbreak highlighted the need to provide
      access to rapid, safe and reliable Ebola Virus Disease diagnostics. OBJECTIVES:
      The objective of this field study was to assess the clinical performance of the
      FilmArray(r) BioThreat-E test for the detection of Ebola Zaire virus in whole
      blood in symptomatic patients suspected of Ebola Virus Disease in Conakry
      (Guinea) from March to July 2015. STUDY DESIGN: The BioThreat-E test was compared
      to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency
      context: an in-house developed quantitative one-step RT-PCR adapted from the
      Weidmann technique, and the RealStar(r) Filovirus RT-PCR Kit 1.0 (Altona
      Diagnostics). We also assessed the performance of this assay in noninvasive
      specimens (urine and saliva) to detect infected patients. RESULTS: Of 135
      patients enrolled and eligible for performance assessment on whole blood, the
      sensitivity was 95.7% [95% CI: 85.5-99.5] and specificity 100% [95% CI: 95.9
      100]. Of the 37 symptomatic infected patients able to provide saliva and/or urine
      samples, 34 of the 35 saliva samples and all 3 of the urine samples were positive
      with the BioThreat-E test. CONCLUSIONS: This study showed that the FilmArray
      BioThreat-E test performs comparably to conventional molecular tests under field
      conditions, providing results and interpretation in approximately 1h. Due to its
      operational characteristics, it can be easily deployed in the field during an
      epidemic and could also be a useful tool for post-outbreak surveillance.

PMID- 28505572
TI  - Challenges in using allylthiourea and chlorate as specific nitrification
      inhibitors.
AB  - Allylthiourea (ATU) and chlorate (ClO3-) are often used to selectively inhibit
      nitritation and nitratation. In this work we identified challenges with use of
      these compounds in inhibitory assays with filter material from a biological rapid
      sand filter for groundwater treatment. Inhibition was investigated in continuous
      flow lab-scale columns, packed with filter material from a full-scale filter and
      supplied with NH4+ or NO2-. ATU concentrations of 0.1-0.5 mM interfered with the
      indophenol blue method for NH4+ quantification leading to underestimation of the
      measured NH4+ concentration. Interference was stronger at higher ATU levels and
      resulted in no NH4+ detection at 0.5 mM ATU. ClO3- at typical concentrations for
      inhibition assays (1-10 mM) inhibited nitratation by less than 6%, while
      nitritation was instead inhibited by 91% when NH4+ was supplied. On the other
      hand, nitratation was inhibited by 67-71% at 10-20 mM ClO3- when NO2- was
      supplied, suggesting significant nitratation inhibition at higher NO2-
      concentrations. No chlorite (ClO2-) was detected in the effluent, and thus we
      could not confirm that nitritation inhibition was caused by ClO3- reduction to
      ClO2-. In conclusion, ATU and ClO3- should be used with caution in inhibition
      assays, because analytical interference and poor selectivity for the targeted
      process may affect the experimental outcome and compromise result interpretation.

PMID- 28505571
TI  - Re-evaluation of routine dengue virus serology in travelers in the era of Zika
      virus emergence.
AB  - BACKGROUND: Diagnostic requests for both Zika virus (ZIKV) and dengue virus
      (DENV) infections in returning travelers have significantly increased during the
      recent ZIKV outbreak in the Americas. These flaviviruses have overlapping
      clinical syndromes and geographical distribution, but diagnostic differentiation
      is important because of different clinical consequences. As flaviviruses are
      known to have a short viremic period, diagnostics often rely on serological
      methods, which are challenging due to extensive cross-reactive antibodies.
      OBJECTIVE: To re-evaluate the performance of DENV serological assays in
      laboratory confirmed ZIKV-infected travelers. STUDY DESIGN: The extent of cross
      reactivity of the DENV NS1 antigen, IgM and IgG ELISA was analyzed in 152
      clinical blood samples collected from 69 qRT-PCR and 24 virus neutralization
      titer (VNT) confirmed ZIKV-infected travelers. RESULTS: The majority of travelers
      in the presented cohort returned to the Netherlands from Suriname and presented
      with symptoms of fever and rash. Twenty-three percent of the female travelers
      were pregnant. None of the 39 ZIKV RNA positive blood samples were cross-reactive
      in the DENV NS1 antigen ELISA. The rates of cross-reactivity of the DENV IgM and
      IgG ELISAs were 31% and 54%, respectively, after excluding travelers with
      (potential) previous DENV exposure. CONCLUSIONS: Although the DENV NS1 antigen
      assay was highly specific in this cohort of laboratory confirmed ZIKV-infected
      travelers, we demonstrate high percentages of cross-reactivity of DENV IgM and
      IgG ELISAs of which diagnostic laboratories should be aware. In addition, the
      high rate of DENV IgG background of >25% complicates a proper serological
      diagnosis in this group.

PMID- 28505573
TI  - Effect of inorganic regenerant properties on pharmaceutical adsorption and
      desorption performance on polymer anion exchange resin.
AB  - This study investigated the potential effect of four frequently used inorganic
      regenerant properties (i.e., ionic strength, cation type, anion type, and
      regeneration solution volume) on the desorption and adsorption performance of 14
      pharmaceuticals, belonging to 12 therapeutic classes with different predominant
      chemical forms and hydrophobicities, using polymeric anion exchange resin (AER)
      packed fixed-bed column tests. After preconditioning with NaCl, NaOH, or saline
      alkaline (SA) solutions, all resulting mobile counterion types of AERs
      effectively adsorbed all 14 pharmaceuticals, where the preferential magnitude of
      OH--type = Cl- + OH--type > Cl--type. During regeneration, ionic strength (1 M
      versus 3 M NaCl) had no significant influence on desorption performance for any
      of the 14 pharmaceuticals, while no regenerant cation (HCl versus NaCl) or anion
      type (NaCl versus NaOH and SA) achieved higher desorption efficiencies for all
      pharmaceuticals. A volumetric increase in 1 M or 3 M NaCl solutions significantly
      improved the desorption efficiencies of most pharmaceuticals, irrespective of
      ionic strength. The results indicate that regeneration protocols, including
      regenerant cation type, anion type and volume, should be optimized to improve
      pharmaceutical removal by AERs.

PMID- 28505574
TI  - The effect of insecticides chlorpyrifos, alpha-cypermethrin and imidacloprid on
      primary DNA damage, TP 53 and c-Myc structural integrity by comet-FISH assay.
AB  - In parallel with the continuous use of conventional insecticides, introduction of
      more environmentally friendly substances continues to grow in modern agriculture.
      In the present study, we evaluated chlorpyrifos, and imidacloprid and alpha
      cypermethrin as two representatives of green insecticides for their genotoxic
      activity. We conducted a 14-day treatment in extended human lymphocytes cultures
      using real life exposure relevant concentrations. An alkaline comet assay was
      used to detect primary DNA damage. Simultaneously, the effect on the specific
      action towards the TP 53 and c-Myc genes in terms of fragmentation and copy
      number were determined. Both genes are responsible for cell cycle regulation;
      thus playing an active role in carcinogenesis. Contrary to what was expected,
      imidacloprid showed the highest genotoxicity potential, irrespective of the fact
      that none of the insecticides induced a significant level of primary DNA damage
      at all tested concentrations. Similar, no significant effect towards the TP 53
      and c-Myc gene was recorded. The present study indicates that low level use of
      chlorpyrifos as a conventional insecticide and imidacloprid and alpha
      cypermethrin as green insecticides does not pose a risk to DNA in general, nor to
      the TP 53 and c-Myc gene structural integrity.

PMID- 28505575
TI  - Synthesis, characterization and photocatalytic properties of nanostructured
      CoFe2O4 recycled from spent Li-ion batteries.
AB  - In this study, cobalt (Co) was recycled from spent lithium ion batteries (LIBs)
      and used to synthesize cobalt ferrite (CoFe2O4-LIBs), which was applied as a
      catalyst for heterogeneous photo Fenton reactions that discolored methylene blue
      (MB) dye. The co-precipitation method was used to synthesize CoFe2O4-LIBs and
      CoFe2O4-R nanoparticles with spinel structures using as raw materials of the LIB
      cathodes and commercial reagents. X-ray diffraction (XRD) identified the
      formation of spinel-type CoFe2O4, which formed clusters that could be seen under
      scanning electron microscopy (SEM) analysis and nanometric particles seen under
      transmission electron microscopy (TEM). Inductively Coupled Plasma Optical
      Emission Spectrometer (ICP OES) analysis was used to determine the concentrations
      of metals present in the ferrite, which reached 6.5% (w/w) of Co. The optimal
      conditions for discoloring the dye were evaluated using a factorial design. Using
      CoFe2O4 as a catalyst, the best conditions for catalytic reaction were pH 3, 30.0
      mg of catalyst, and 8.0 mL of H2O2 73% (v/v). Discoloration efficiencies of 87.3%
      and 87.7% were obtained from CoFe2O4-R and CoFe2O4-LIBs, respectively. Therefore,
      CoFe2O4-LIBs proved to be an efficient catalyst for discoloring MB dye using
      heterogeneous photo-Fenton reactions. This work is of scientific, social,
      economic, and environmental interest. It investigates the process of
      synthesizing,characterizing CoFe2O4LIBs and the efficiency of degrading MB dye,
      subjects that have economic and environmental, and therefore, social interest.
      The work has scientific interest particularly because of the correlation between
      the structure of the recycled material and its catalytic properties.

PMID- 28505576
TI  - Toxicity of environmentally realistic concentrations of chlorpyrifos and
      terbuthylazine in indoor microcosms.
AB  - Few studies have been conducted into the evaluation of environmentally realistic
      pesticide mixtures using model ecosystems. In the present study, the effects of
      single and combined environmentally realistic concentrations of the herbicide
      terbuthylazine and the insecticide chlorpyrifos were evaluated using laboratory
      microcosms. Direct toxic effects of chlorpyrifos were noted on copepod nauplii
      and cladocerans and the recovery of the latter was likely related with the
      decrease observed in rotifer abundances. Terbuthylazine potentiated the effect of
      chlorpyrifos on feeding rates of Daphnia magna, presumably by triggering the
      transformation of chlorpyrifos to more toxic oxon-analogs. Possible food-web
      interactions resulting from multiple chemical (and other) stressors likely to be
      present in edge-of-field water bodies need to be further evaluated.

PMID- 28505577
TI  - Evaluation of the photooxidation efficiency of As(III) applying the UVC/oxalate
      technique.
AB  - In this study, the photooxidation capacity of UVC/Oxalate (Ox) was evaluated
      using As(III) as a typical pollutant. The results show that the direct oxidation
      amount of As(III) induced by UVC in water was negligible, but the presence of Ox
      remarkably accelerated the oxidation rate of As(III). Under UVC irradiation, 50
      MUM As(III) can be completely oxidized to As(V) in the case of Ox concentration
      above 300 MUM within 60 min. As(III) oxidation was found greatly related with the
      photodecomposition of Ox. Much more Ox can be mineralized in more acidic
      solution. At the same time, the photooxidation of As(III) was significantly
      favored at decreased initial pH from 8.0 to 3.0. In this reaction system, the
      role of oxygen was indispensable for Ox photodecomposition and As(III)
      photooxidation, which can be ascribed to its special roles as a precursor of
      reactive superoxide and an electron acceptor. In oxygen-present atmosphere, the
      in situ production of H2O2 was detected during the photolysis of Ox and its
      photolysis product, i.e., OH primarily contributed to the oxidation of As(III).
      However, the photodecomposition of Ox and photooxidation of As(III) were
      significantly inhibited in the anaerobic environment. In general, the homogeneous
      photolysis of Ox in many commonly practiced UVC oxidation processes can be also
      proposed as a supplementary method of generating highly oxiditive species in
      aerobic condition.

PMID- 28505578
TI  - The use of reactive index of hydroxyl radicals to investigate the degradation of
      acid orange 7 by Fenton process.
AB  - This study suggested the amount of hydroxyl radicals (OH) reacting with organics
      as a new index to evaluate the reaction efficiency (RE) of Fenton process, and
      used it to investigate the degradation mechanism of target pollution, Acid Orange
      7 (AO7). The effects of initial concentrations of Fe(II), H2O2, and AO7 on RE
      were quantified by using response surface methodology (RSM). The main factors
      affecting RE were Fe(II), H2O2, and their interaction, and their percentage
      effects were 65.75, 11.99 and 22.23%, respectively. Moreover, based on the
      analysis result of RSM, a condition for good RE was proposed that it should
      ensure a higher amount of OH reacted with organics, and reduce the amount of OH
      scavenged by Fe(II). Liquid chromatography-mass spectrometry (LC/MS) analysis was
      used to identify the products of AO7 degradation in Fenton process, and there
      were three possible mechanisms to be observed, such as azo bond cleavage,
      hydroxylation, and oxidation of naphthalene ring. The trend of mechanisms might
      vary with the amount of OH attacks, and therefore the use of estimated RE could
      provide more particular information to better understand the relationship between
      organic degradation and OH attacks.

PMID- 28505579
TI  - Effect of Lupinus albus L. root activities on As and Cu mobility after addition
      of iron-based soil amendments.
AB  - Arsenic and Cu mobility was investigated in the rhizosphere of Lupinus albus L.
      grown in an iron-amended contaminated soil. White lupin was grown in rhizobags in
      contaminated soil either left untreated or amended with iron sulphate plus lime
      (Fe + lime) or biochar (Fe + BC). Porewater was monitored in rhizosphere and bulk
      soil throughout the experiment and the extractable fraction of several elements
      and As and Cu plant uptake was analysed after 48 days. The distribution of As,
      Cu, P and Fe in the lupin rhizosphere was evaluated with chemical images obtained
      by laser ablation-ICP-MS analysis of diffusive gradients in thin films (DGT)
      gels. The treatments effectively reduced the soluble and extractable As and Cu
      fractions in the bulk soil, but they did not affect plant uptake. In all cases,
      soluble As was slightly enhanced in the rhizosphere. This difference was more
      pronounced in the Fe + lime-treated rhizosphere soil, where an increase of pH as
      well as extractable As and Fe concentrations were also observed. Chemical imaging
      of the lupin rhizosphere also showed slightly higher As- and Fe-DGT fluxes around
      lupin roots grown in the non-amended soil. Our findings indicate As and Fe co
      solubilisation by lupin root exudates, likely as a response to P deficiency.
      Arsenic mobilisation occurred only in the rhizosphere and was not decreased by
      the amendments.

PMID- 28505580
TI  - Factors affecting perceived change in physical activity in pregnancy.
AB  - OBJECTIVE: reduction of physical activity (PA) during pregnancy is common but
      undesirable, as it is associated with negative outcomes, including excessive
      gestational weight gain. Our objective was to explore changes in five types of
      activity that occurred during pregnancy and the behavioural determinants of the
      reported changes in PA. DESIGN: we performed a secondary analysis of a cross
      sectional survey that was constructed using the ASE-Model - an approach to
      identifying the factors that drive behaviour change that focuses on Attitude,
      Social influence, and self-Efficacy. PARTICIPANTS: 455 healthy pregnant women of
      all gestational ages, receiving prenatal care from midwifery practices in the
      Netherlands. FINDINGS: more than half of our respondents reported a reduction in
      their PA during pregnancy. The largest reduction occurred in sports and brief
      rigorous activities, but other types of PA were reduced as well. Reduction of PA
      was more likely in women who considered themselves as active before pregnancy,
      women who experienced pregnancy-related barriers, women who were advised to
      reduce their PA, and multiparous women. Fewer than 5% increased their PA.
      Motivation to engage in PA was positively associated with enjoying PA. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: all pregnant women should be informed
      about the positive effects of staying active and should be encouraged to engage
      in, or to continue, moderately intensive activities like walking, biking or
      swimming. Our findings concerning the predictors of PA reduction can be used to
      develop an evidence-based intervention aimed at encouraging healthy PA during
      pregnancy.

PMID- 28505581
TI  - Spatiotemporal reorganization of the reading network in adult dyslexia.
AB  - Developmental dyslexia is characterized by impairments in reading fluency and
      spelling that persist into adulthood. Here, we hypothesized that high-achieving
      adult dyslexics (i.e., university students with a history of dyslexia) manage to
      cope with these deficits by relying to a greater extent on morphological
      information than do non-impaired adult readers. We used magnetoencephalography
      (MEG) in a primed lexical decision task, in which we contrasted orthographic,
      morphological and semantic processing. Behavioral results confirmed that adult
      dyslexics did indeed rely to a greater extent on the semantic properties of
      morphemes than controls. In line with this, MEG results showed early
      morphological effects (100-200 msec) in a frontal network, which reflected the
      contribution of semantic processing. The same effects occurred much later in
      controls (~400 msec). In contrast, controls showed early orthographic priming
      effects in posterior left inferior temporal gyrus (LITG) at around 130 msec,
      which were not seen in dyslexics. In the LITG, dyslexics showed only late
      activation of semantic and orthographic information. The present results suggest
      a spatiotemporal reorganization of the reading network, in which morphological
      information located in frontal regions is activated earlier in high-achieving
      adults dyslexics than controls.

PMID- 28505582
TI  - Plastic potential: how the phenotypes and adaptations of pathogens are influenced
      by microbial interactions within plants.
AB  - Predicting the effects of plant-associated microbes on emergence, spread, and
      evolution of plant pathogens demands an understanding of how pathogens respond to
      these microbes at two levels of biological organization: that of an individual
      pathogen and that of a pathogen population across multiple individual plants. We
      first examine the plastic responses of individual plant pathogens to microbes
      within a shared host, as seen through changes in pathogen growth and
      multiplication. We then explore the limited understanding of how within-plant
      microbial interactions affect pathogen populations and discuss the need to
      incorporate population-level observations with population genomic techniques.
      Finally, we suggest that integrating across levels will further our understanding
      of the ecological and evolutionary impacts of within-plant microbial interactions
      on pathogens.

PMID- 28505583
TI  - Immunity and starvation: new opportunities to elevate disease resistance in
      crops.
AB  - Plants use multiple mechanisms to defend themselves against invading microbes.
      Besides using their immune system to surveil and eliminate pathogens, plants
      actively block the pathogens' access to nutrients as an alternative way to
      prevent colonization. In this review, we focus on immunity and starvation as
      major obstacles for pathogens' adaptation. We summarize the key mechanisms
      employed by pathogens to modulate host immunity and to guarantee sugar uptake. In
      contrast to genes that deal with the immune system and show high levels of
      plasticity, pathogen genes involved in sugar acquisition are highly conserved,
      and may not have adapted to co-evolving interactions with the host. We propose a
      model to assess the durability of different control strategies based on the
      ability of pathogens to deal with host immunity or starvation. This analysis
      opens new opportunities to elevate disease resistance in crops by reducing the
      likelihood of pathogen adaptation.

PMID- 28505584
TI  - Development of a gold nanoparticle-based universal oligonucleotide microarray for
      multiplex and low-cost detection of foodborne pathogens.
AB  - Bacterial foodborne diseases remain major threats to food safety and public
      health, especially in developing countries. In this study a novel assay,
      combining gold nanoparticle (GNP)-based multiplex oligonucleotide ligation-PCR
      and universal oligonucleotide microarray technology, was developed for
      inexpensive, specific, sensitive, and multiplex detection of eight common
      foodborne pathogens, including Shigella spp., Campylobacter jejuni, Bacillus
      cereus, Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica,
      Staphylococcus aureus, and Vibrio parahaemolyticus. The target fragments of the
      eight pathogens were enriched by multiplex PCR and subjected to multiplex ligase
      detection reaction. Ligation products were enriched and labeled with GNPs by
      universal asymmetric PCR, using excess GNP-conjugated primers. The labeled single
      stranded amplicons containing complementary tag sequences were captured by the
      corresponding tag sequences immobilized on microarrays, followed by silver
      staining for signal enhancement. Black images of microarray spots were visualized
      by naked eyes or scanned on a simple flatbed scanner, and quantified. The results
      indicated that this assay could unambiguously discriminate all eight pathogens in
      single and multiple infections, with detection sensitivity of 3.3-85CFU/mL for
      pure cultures. Microarray results of ninety-five artificially contaminated and
      retail food samples were consistent with traditional culture, biochemical and
      real-time PCR findings. Therefore, the novel assay has the potential to be used
      for routine detection due to rapidity, low cost, and high specificity and
      sensitivity.

PMID- 28505585
TI  - Giant hepatocellular carcinoma with bone metastasis in a young adult, emerged
      from pigmented adenoma with beta-Catenin activation: A case report.
AB  - INTRODUCTION: Hepatocellular carcinomas (HCC) that are very large in size are a
      very rare finding in young adult. The malignant transformation of a pigmented
      hepatocellular adenoma (HCA) with beta-Catenin activation is a possible cause for
      appearance of HCC. PRESENTATION OF CASE: We present the case of a 33-year-old
      male with a huge HCC with bone metastasis, emerged from pigmented HCA with beta
      Catenin activation. As a two-stage surgical procedure, a left hepatectomy
      followed by a partial rib resection was performed. DISCUSSION: Giant
      hepatocellular carcinomas mostly develop in non-cirrhotic livers and at time of
      diagnosis an extrahepatic spread occurs in up to 15%. In the present case, the
      progression from a benign HCA to malignant HCC was documented, as a unique
      finding. Surgical resection is the only curative treatment and was successfully
      performed in this case. CONCLUSION: Hepatobiliary surgery with resection of
      metastases is the treatment with best long-term survival for patients with huge
      HCC. Molecular characterization as well as pigmentation analysis is useful tools
      for risk assessment of HCA.

PMID- 28505586
TI  - Oscillatory magnetic brain activity is related to dissociative symptoms and
      childhood adversities - A study in women with multiple trauma.
AB  - BACKGROUND: Individuals with trauma-related disorders are complex and
      heterogeneous; part of this complexity derives from additional psychopathology
      like dissociation as well as environmental adversities such as traumatic stress,
      experienced throughout the lifespan. Understanding the neurophysiological
      abnormalities in Post-traumatic stress disorder (PTSD) requires a simultaneous
      consideration of these factors. METHODS: Resting state magnetoencephalography
      (MEG) recordings were obtained from 41 women with PTSD and comorbid depressive
      symptoms, and 16 healthy women. Oscillatory brain activity was extracted for five
      frequency bands and 11 source locations, and analyzed in relation to shutdown
      dissociation and adversity-related measures. RESULTS: Dissociative symptoms were
      related to increased delta and lowered beta power. Adversity-related measures
      modulated theta and alpha oscillatory power (in particular childhood sexual
      abuse) and differed between patients and controls. LIMITATIONS: Findings are
      based on women with comorbid depressive symptoms and therefore may not be
      applicable for men or groups with other clinical profiles. In respect to
      childhood adversities, we had no reliable source for the early infancy.
      CONCLUSION: Trauma-related abnormalities in neural organization vary with both
      exposure to adversities as well as their potential to evoke ongoing shutdown
      responses.

PMID- 28505587
TI  - Dietary Bacillus subtilis-based direct-fed microbials alleviate LPS-induced
      intestinal immunological stress and improve intestinal barrier gene expression in
      commercial broiler chickens.
AB  - This study investigated the effects of Bacillus subtilis-based probiotics on the
      performance, modulation of host inflammatory responses and intestinal barrier
      gene expression of broilers subjected to LPS challenge. Chickens were randomly
      allocated to one of the 3 dietary treatment groups - control, antibiotic, or
      probiotic. At 14days, half of the chickens in each treatment were injected with
      LPS (1mg/kg body weight), and the other half injected with sterile PBS. Chickens
      fed probiotics weighed significantly more than controls at 15days of age,
      irrespective of immune challenge. LPS challenge significantly reduced weight gain
      at 24h post-injection, and the probiotics did not alleviate the LPS-induced
      reduction of weight gain. Serum alpha-1-AGP levels were significantly higher in
      LPS-injected chickens, and probiotic supplementation significantly reduced their
      levels. The percentages of CD4+ lymphocytes were significantly increased in
      probiotic groups in the absence of immunological challenge but were reduced
      during LPS challenge compared to controls. CD8+ lymphocytes were significantly
      reduced in probiotic-fed birds. The LPS-induced increase in the expression of
      cytokines IL8 and TNFSF15 was reduced by probiotic supplementation, and IL17F,
      iNOS expression was found to be significantly elevated in probiotic-fed birds
      subjected to LPS challenge. The reduced gene expression of tight junction
      proteins (JAM2, occludin and ZO1) and MUC2 induced by LPS challenge was reversed
      by probiotic supplementation. The results indicate that B. subtilis-based
      probiotics differentially regulate intestinal immune and tight junction protein
      mRNA expression during states of LPS-mediated immunological challenge.

PMID- 28505588
TI  - Hydroxylated 2-Ethylhexyl tetrabromobenzoate isomers in house dust and their
      agonistic potencies with several nuclear receptors.
AB  - In the current study, by combining ultra-high resolution (UHR) MS1 spectra, MS2
      spectra, and derivatization, three hydroxylated isomers of 2-ethylhexyl
      tetrabromobenzoate (OH-TBB) were identified in Firemaster(r) 550 and BZ-54
      technical products. Also, a new LC-UHRMS method, using atmospheric pressure
      chemical ionization (APCI), was developed for simultaneous analysis of OH-TBB,
      TBB, hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) and TBPH in 23
      samples of dust collected from houses in Saskatoon, SK, Canada. OH-TBBs were
      detected in 91% of samples, with a geometric mean concentration of 0.21 ng/g,
      which was slightly less than those of OH-TBPH (0.35 ng/g). TBB was detected in
      100% of samples of dust with a geometric mean concentration of 992 ng/g.
      Significant (p < 0.001) log-linear relationships between concentrations of OH
      TBBs, TBB, or OH-TBPHs and TBPH in dust support the hypothesis of a common source
      of these compounds. OH-TBBs were found to be strong agonists of peroxisome
      proliferator-activated receptor gamma (PPARgamma) and weaker agonists of the
      estrogen receptor (ER), but no agonistic potencies was observed with the androgen
      receptor (AR). Occurrence of OH-TBBs in technical products and house dust,
      together with their relatively strong PPARgamma potencies, indicated their
      potential risk to health of humans.

PMID- 28505589
TI  - Multi-platform metabolomics and a genetic approach support the authentication of
      agarwood produced by Aquilaria crassna and Aquilaria malaccensis.
AB  - Agarwood, the resinous heartwood produced by some Aquilaria species such as
      Aquilaria crassna, Aquilaria malaccensis and Aquilaria sinensis, has been
      traditionally and widely used in medicine, incenses and especially perfumes.
      However, up to now, the authentication of agarwood has been largely based on
      morphological characteristics, a method which is prone to errors and lacks
      reproducibility. Hence, in this study, we applied metabolomics and a genetic
      approach to the authentication of two common agarwood chips, those produced by
      Aquilaria crassna and Aquilaria malaccensis. Primary metabolites, secondary
      metabolites and DNA markers of agarwood were authenticated by 1H NMR
      metabolomics, GC-MS metabolomics and DNA-based techniques, respectively. The
      results indicated that agarwood chips could be classified accurately by all the
      methods illustrated in this study. Additionally, the pros and cons of each method
      are also discussed. To the best of our knowledge, our research is the first study
      detailing all the differences in the primary and secondary metabolites, as well
      as the DNA markers between the agarwood produced by these two species.

PMID- 28505590
TI  - Apoptosis induction activity and molecular docking studies of survivin siRNA
      carried by Fe3O4-PEG-LAC-chitosan-PEI nanoparticles in MCF-7 human breast cancer
      cells.
AB  - Delivery of small interfering RNAs (siRNAs) into cells still remains a challenge
      in gene delivery studies. Here, we investigated the ability of synthesized Fe3O4
      PEG-LAC-chitosan-PEI nanoparticles for siRNA delivery of survivin as the model
      gene into cells. The cellular uptake of survivin siRNA carried by synthesized
      nanoparticles into MCF-7 breast cancer cell line was evaluated by florescent
      microscopy and flowcytometry, both proving the efficacy of nanoparticles in
      delivery of up to 64.7% in comparison with lipofectamine 2000. Furthermore, the
      delivery of survivin siRNA by the nanoparticles (nanoplex) induced apoptosis that
      was assessed through DAPI staining and Annexin V/PI assays. In addition, we
      evaluated the efficacy of treatment with nanoplexes in the presence of
      mitoxantrone, as a chemotherapeutic agent. Our data indicated that inhibition of
      survivin expression increased the cell sensitivity to mitoxantrone. Real-time PCR
      and western blotting analysis revealed a significant reduction in mRNA and
      protein levels of survivin upon delivery of siRNA. Molecular docking studies
      showed that nanoparticles can bind to centeral BIR domain of survivin, exactly
      above zinc ion location with high affinity (DeltaG: -10.3Kcal/mol). Also,
      thermodynamic studies proved the experimental results theoretically, revealing
      that the siRNA-loaded nanoparticles have a suppressing effect on survivin mRNA.
      Therefore, delivery of survivin siRNA into MCF-7 cells using Fe3O4-PEG-LAC
      chitosan-PEI nanoparticles as a carrier enhances the cell death.

PMID- 28505591
TI  - Factors associated with serum thyroglobulin in a Ukrainian cohort exposed to
      iodine-131 from the accident at the Chernobyl Nuclear Plant.
AB  - BACKGROUND: Serum thyroglobulin (Tg) is associated with the presence of thyroid
      disease and has been proposed as a biomarker of iodine status. Few studies have
      examined factors related to serum Tg in populations environmentally exposed to
      ionizing radiation and living in regions with endemic mild-to-moderate iodine
      deficiency. METHODS: We screened 10,430 individuals who were living in Ukraine
      and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant
      accident for thyroid disease from 2001 to 2003. We estimated the percent change
      (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose,
      and indicators of thyroid structure and function using linear regression. We also
      examined these relationships for individuals with and without indications of
      thyroid abnormality. RESULTS: Mean and median serum Tg levels were higher among
      participants with abnormal thyroid structure/function. Percent change in serum Tg
      increased among females, smokers and with older age (p-values<0.001), and Tg
      increased with increasing thyroid volume, and serum thyrotropin (p-values for
      trend<0.001). We found no evidence of significant associations between iodine-131
      thyroid dose and Tg. Serum Tg levels were inversely associated with iodized salt
      intake (PC=-7.90, 95% confidence interval: -12.08, -3.52), and over the range of
      urinary iodine concentration, the odds of having elevated serum Tg showed a U
      shaped curve with elevated Tg at low and high urinary iodine concentrations.
      CONCLUSION: Serum Tg may be a useful indicator of population iodine status and a
      non-specific biomarker of structural and functional thyroid abnormalities in
      epidemiological studies.

PMID- 28505592
TI  - Human norovirus inhibition by a human milk oligosaccharide.
AB  - Human noroviruses are the leading cause of outbreaks of acute gastroenteritis.
      Norovirus interactions with histo-blood group antigens (HBGAs) are known to be
      important for an infection. In this study, we identified the HBGA binding pocket
      for an emerging GII genotype 17 (GII.17) variant using X-ray crystallography. The
      GII.17 variant bound the HBGA with an equivalent set of residues as the leading
      pandemic GII.4 variants. These structural data highlights the conserved nature of
      HBGA binding site between prevalent GII noroviruses. Noroviruses also interact
      with human milk oligosaccharides (HMOs), which mimic HBGAs and may function as
      receptor decoys. We previously showed that HMOs inhibited the binding of rarely
      detected GII.10 norovirus to HBGAs. We now found that an HMO, 2'-fucosyllactose
      (2'FL), additionally blocked both the GI.1 and GII.17 noroviruses from binding to
      HBGAs. Together, these findings provide evidence that 2'FL might function as a
      broadly reactive antiviral against multiple norovirus genogroups.

PMID- 28505593
TI  - Foot-ankle complex injury risk curves using calcaneus bone mineral density data.
AB  - OBJECTIVE: Biomechanical data from post mortem human subject (PMHS) experiments
      are used to derive human injury probability curves and develop injury criteria.
      This process has been used in previous and current automotive crashworthiness
      studies, Federal safety standards, and dummy design and development. Human bone
      strength decreases as the individuals reach their elderly age. Injury risk curves
      using the primary predictor variable (e.g., force) should therefore account for
      such strength reduction when the test data are collected from PMHS specimens of
      different ages (age at the time of death). This demographic variable is meant to
      be a surrogate for fracture, often representing bone strength as other parameters
      have not been routinely gathered in previous experiments. However, bone mineral
      densities (BMD) can be gathered from tested specimens (presented in this
      manuscript). The objective of this study is to investigate different approaches
      of accounting for BMD in the development of human injury risk curves. METHODS:
      Using simulated underbody blast (UBB) loading experiments conducted with the PMHS
      lower leg-foot-ankle complexes, a comparison is made between the two methods:
      treating BMD as a covariate and pre-scaling test data based on BMD. Twelve PMHS
      lower leg-foot-ankle specimens were subjected to UBB loads. Calcaneus BMD was
      obtained from quantitative computed tomography (QCT) images. Fracture forces were
      recorded using a load cell. They were treated as uncensored data in the survival
      analysis model which used the Weibull distribution in both methods. The width of
      the normalized confidence interval (NCIS) was obtained using the mean and +/- 95%
      confidence limit curves. PRINCIPAL RESULTS: The mean peak forces of 3.9kN and
      8.6kN were associated with the 5% and 50% probability of injury for the covariate
      method of deriving the risk curve for the reference age of 45 years. The mean
      forces of 5.4 kN and 9.2kN were associated with the 5% and 50% probability of
      injury for the pre-scaled method. The NCIS magnitudes were greater in the
      covariate-based risk curves (0.52-1.00) than in the risk curves based on the pre
      scaled method (0.24-0.66). The pre-scaling method resulted in a generally greater
      injury force and a tighter injury risk curve confidence interval. Although not
      directly applicable to the foot-ankle fractures, when compared with the use of
      spine BMD from QCT scans to pre-scale the force, the calcaneus BMD scaled data
      produced greater force at the same risk level in general. CONCLUSIONS: Pre
      scaling the force data using BMD is an alternate, and likely a more accurate,
      method instead of using covariate to account for the age-related bone strength
      change in deriving risk curves from biomechanical experiments using PMHS. Because
      of the proximity of the calcaneus bone to the impacting load, it is suggested to
      use and determine the BMD of the foot-ankle bone in future UBB and other loading
      conditions to derive human injury probability curves for the foot-ankle complex.

PMID- 28505594
TI  - The rheological behavior of a fast-setting calcium phosphate bone cement and its
      dependence on deformation conditions.
AB  - Calcium phosphate cements are osteoconductive biomaterials that are widely used
      for bone repair and regeneration applications, including spinal fusion,
      vertebroplasty, khyphoplasty, cranioplasty and periodontal surgeries. The flow
      and deformation behavior (rheology) and injectability of the calcium phosphate
      bone cements to the treatment site are governed by the setting kinetics of the
      cement during which the initially flowable, viscous cement paste transforms into
      a rigid elastic solid. Here time-dependent development of the linear viscoelastic
      properties of a brushite-forming calcium phosphate cement are characterized and
      linked to the mechanism and kinetics of the setting reaction and to the
      injectability window available during the surgical applications of the cement.
      The setting kinetics is shown to be a function of the deformation conditions that
      are utilized in rheological characterization, emphasizing the intimate
      relationships between setting kinetics, particle to particle network formation
      and deformation history. Furthermore, the preshearing of the calcium phosphate
      cement prior to injection and temperature are shown to alter the kinetics of the
      setting reaction and thus to provide additional degrees of freedom for the
      tailoring of the rheological behavior and injectability of the calcium phosphate
      cement.

PMID- 28505595
TI  - Epigenetic drug combination induces remission in mouse xenograft models of
      pediatric acute myeloid leukemia.
AB  - Aberrations in epigenetic modifications contribute to leukemogenesis in childhood
      acute myeloid leukemia (AML). We combined DNA hypomethylating agent azacitidine
      with histone deacetylase inhibitor panobinostat in preclinical models of
      childhood AML. Synergistic cytotoxic effect upon treatment with azacitidine and
      panobinostat with combination indices <1.0 was observed. Azacitidine and
      panobinostat increased median survival by 26 and 6days respectively in MV4;11
      xenografted mice. Mice treated with both drugs showed a drastic reduction in
      leukemic burden leading to complete remission sustained for the duration of the
      experimental period lasting more than 519days. Reduced leukemic burden and
      prolonged survival was also observed in AML-193 xenografted mice treated with
      azacitidine-panobinostat combination. Differential gene expression profiling was
      performed on AML cells treated with azacitidine, panobinostat or azacitidine
      panobinostat combination. Functional mapping of transcripts uniquely regulated by
      the azacitidine-panobinostat combination in MV4;11 cells identified p53 as an
      upstream regulator. A comparison of the uniquely modulated transcripts by
      azacitidine-panobinostat combination in MV4;11 cells versus AML-193 and THP-1
      cells, bearing mutated p53, also revealed p53 as the topmost upstream regulator.
      Finally, expression of mutant p53 in MV4;11 cells reduced sensitivity to
      azacitidine-panobinostat combination, suggesting that p53 may be a predictor of
      response to epigenetic therapy in pediatric AML.

PMID- 28505596
TI  - Engineered hydrogels increase the post-transplantation survival of encapsulated
      hESC-derived midbrain dopaminergic neurons.
AB  - Cell replacement therapies have broad biomedical potential; however, low cell
      survival and poor functional integration post-transplantation are major hurdles
      that hamper clinical benefit. For example, following striatal transplantation of
      midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease
      (PD), only 1-5% of the neurons typically survive in preclinical models and in
      clinical trials. In general, resource-intensive generation and implantation of
      larger numbers of cells are used to compensate for the low post-transplantation
      cell-survival. Poor graft survival is often attributed to adverse biochemical,
      mechanical, and/or immunological stress that cells experience during and after
      implantation. To address these challenges, we developed a functionalized
      hyaluronic acid (HA)-based hydrogel for in vitro maturation and central nervous
      system (CNS) transplantation of human pluripotent stem cell (hPSC)-derived neural
      progenitors. Specifically, we functionalized the HA hydrogel with RGD and heparin
      (hep) via click-chemistry and tailored its stiffness to encourage neuronal
      maturation, survival, and long-term maintenance of the desired mDA phenotype.
      Importantly, ~5 times more hydrogel-encapsulated mDA neurons survived after
      transplantation in the rat striatum, compared to unencapsulated neurons harvested
      from commonly used 2D surfaces. This engineered biomaterial may therefore
      increase the therapeutic potential and reduce the manufacturing burden for
      successful neuronal implantation.

PMID- 28505597
TI  - An interpenetrating network-strengthened and toughened hydrogel that supports
      cell-based nucleus pulposus regeneration.
AB  - Hydrogel is a suitable scaffold for the nucleus pulposus (NP) regeneration.
      However, its unmatched mechanical properties lead to implant failure in late
      stage disc degeneration because of structural failure and implant extrusion after
      long-term compression. In this study, we evaluated an interpenetrating network
      (IPN)-strengthened and toughened hydrogel for NP regeneration, using dextran and
      gelatin as the primary network while poly (ethylene glycol) as the secondary
      network. The aim of this study was to realize the NP regeneration using the
      hydrogel. To achieve this, we optimized its properties by adjusting the mass
      ratios of the secondary/primary networks and determining the best preparation
      conditions for NP regeneration in a series of biomechanical, cytocompatibility,
      tissue engineering, and in vivo study. We found the optimal formulation of the
      IPN hydrogel, at a secondary/primary network ratio of 1:4, exhibited high
      toughness (the compressive strain reached 86%). The encapsulated NP cells showed
      increasing proliferation, cell clustering and matrix deposition. Furthermore, the
      hydrogel could support long-term cell retention and survival in the rat IVDs. It
      facilitated rehydration and regeneration of porcine degenerative NPs. In
      conclusion, this study demonstrates the tough IPN hydrogel could be a promising
      candidate for functional disc regeneration in future.

PMID- 28505598
TI  - Interlocked DNA topologies for nanotechnology.
AB  - Interlocked molecular architectures are well known in supramolecular chemistry
      and are widely used for various applications like sensors, molecular machines and
      logic gates. The use of DNA for constructing these interlocked structures has
      increased significantly within the current decade. Because of Watson-Crick base
      pairing rules, DNA is an excellent material for the self-assembly of well-defined
      interlocked nanoarchitectures. These DNA nanostructures exhibit sufficient
      stability, good solubility in aqueous media, biocompatibility, and can be easily
      combined with other biomolecules in bio-hybrid nano-assemblies. Therefore, the
      study of novel DNA-based interlocked systems is of interest for nanotechnology,
      synthetic biology, supramolecular chemistry, biotechnology, and for sensing
      purposes. Here we summarize recent developments and applications of interlocked
      supramolecular architectures made of DNA. Examples illustrating that these
      systems can be precisely controlled by switching on and off the molecular motion
      of its mechanically trapped components are discussed. Introducing different
      triggers into such systems creates molecular assemblies capable of performing
      logic gate operations and/or catalytic activity control. Interlocked DNA-based
      nanostructures thus represent promising frameworks for building increasingly
      complex and dynamic nanomachines with highly controllable functionality.

PMID- 28505599
TI  - A new method for quantifying the performance of EEG blind source separation
      algorithms by referencing a simultaneously recorded ECoG signal.
AB  - Blind source separation (BSS) algorithms extract neural signals from
      electroencephalography (EEG) data. However, it is difficult to quantify source
      separation performance because there is no criterion to dissociate neural signals
      and noise in EEG signals. This study develops a method for evaluating BSS
      performance. The idea is neural signals in EEG can be estimated by comparison
      with simultaneously measured electrocorticography (ECoG). Because the ECoG
      electrodes cover the majority of the lateral cortical surface and should capture
      most of the original neural sources in the EEG signals. We measured real EEG and
      ECoG data and developed an algorithm for evaluating BSS performance. First, EEG
      signals are separated into EEG components using the BSS algorithm. Second, the
      EEG components are ranked using the correlation coefficients of the ECoG
      regression and the components are grouped into subsets based on their ranks.
      Third, canonical correlation analysis estimates how much information is shared
      between the subsets of the EEG components and the ECoG signals. We used our
      algorithm to compare the performance of BSS algorithms (PCA, AMUSE, SOBI, JADE,
      fastICA) via the EEG and ECoG data of anesthetized nonhuman primates. The results
      (Best case >JADE = fastICA >AMUSE = SOBI >= PCA >random separation) were common
      to the two subjects. To encourage the further development of better BSS
      algorithms, our EEG and ECoG data are available on our Web site
      (http://neurotycho.org/) as a common testing platform.

PMID- 28505600
TI  - God imagery and affective outcomes in a spiritually integrative inpatient
      program.
AB  - Religion and/or spirituality (R/S) can play a vital, multifaceted role in mental
      health. While beliefs about God represent the core of many psychiatric patients'
      meaning systems, research has not examined how internalized images of the divine
      might contribute to outcomes in treatment programs/settings that emphasize
      multicultural sensitivity with R/S. Drawing on a combination of qualitative and
      quantitative information with a religiously heterogeneous sample of 241 adults
      who completed a spiritually integrative inpatient program over a two-year period,
      this study tested direct/indirect associations between imagery of how God views
      oneself, religious comforts and strains, and affective outcomes (positive and
      negative). When accounting for patients' demographic and religious backgrounds,
      structural equation modeling results revealed: (1) overall effects for God
      imagery at pre-treatment on post-treatment levels of both positive and negative
      affect; and (2) religious comforts and strains fully mediated these links.
      Secondary analyses also revealed that patients' generally experienced reductions
      in negative emotion in God imagery over the course of their admission. These
      findings support attachment models of the R/S-mental health link and suggest that
      religious comforts and strains represent distinct pathways to positive and
      negative domains of affect for psychiatric patients with varying experiences of
      God.

PMID- 28505601
TI  - The association between attempted suicide and stock price movements: Evidence
      from Taiwan.
AB  - This study is the first comprehensive analysis to investigate the potential
      association between stock market fluctuations and attempted suicide events as
      measured by self-inflicted injuries treated in hospitalization. Using nationwide,
      15-year population-based data from 1998 through 2012, we observe that the
      occurrences for the hospitalizations of attempted suicides are apparently
      predicted by stock price movements. A low stock price index, a daily fall in the
      stock index, and consecutive daily falls in the stock index have been shown to be
      associated with increased risk of hospitalization in patients with attempted
      suicide. More specifically, stock price index is found to be significant impact
      on attempted suicide in the 45-54 age groups of both genders, whilst daily change
      is significant for both genders in the 25-34 and 55-64 age groups and accumulated
      change is only significant in female aged 25-44 and above 65. On the basis of the
      results, relevant organizations should consider the suicidal factors that relate
      prime-working-age and near-retirement-age people to better carry out specific
      suicide prevention measures, and, meanwhile, encourage those people to pay less
      attention towards daily stock price movements.

PMID- 28505603
TI  - Icariin protects against thioacetamide-induced liver fibrosis in rats:
      Implication of anti-angiogenic and anti-autophagic properties.
AB  - BACKGROUND: Liver fibrosis is a major health problem. The current study evaluated
      the potential of icariin (ICA) to guard against thioacetamide (TAA)-induced liver
      fibrosis in rats. METHODS: Four groups of male rats were treated as follows:
      group 1 was the control group, group 2 was given TAA (200mg/kg), group 3 was
      administered ICA (50mg/kg) and TAA (200mg/kg), and group 4 was given ICA
      (50mg/kg) alone. Animal treatment was continued for four weeks. RESULTS: Co
      administration of ICA guarded against TAA hepatotoxicity as indicated by
      significant inhibition in the rise of serum ALT and AST activities and albumin
      concentrations. This was accompanied by inhibition of reduced glutathione
      depletion, superoxide dismutase exhaustion, and lipid peroxide accumulation. In
      addition, ICA inhibited the pathological alterations in liver architecture
      induced by TAA. The antifibrotic activity of ICA was verified by reduced hepatic
      collagen deposition in liver sections stained with Masson's trichrome and hepatic
      Col-1alpha mRNA and hydroxyproline contents compared to the TAA-treated group.
      The antiangiogenic activity of ICA was evidenced by lowered levels of mRNA of Ang
      1 and protein expression of VEGF, PDGF-beta, and CTGF immunohistochemically.
      Further, the anti-autophagic property of ICA was evidenced by amelioration of the
      decrease in mTOR and p70S6 kinase expression and an increase in TLR4, NFkappaB,
      IL1-beta, and COX-2 immunohistochemically. Moreover, ICA antagonized the increase
      in HMGB1, TGF-beta, and Beclin-1 and the decrease in BAMBI hepatic mRNA levels.
      CONCLUSIONS: ICA inhibits TAA-induced liver fibrosis in rats, possibly via
      inhibition of angiogenesis and autophagy.

PMID- 28505602
TI  - Unusual antigen presentation offers new insight into HIV vaccine design.
AB  - Recent findings with a rhesus monkey cytomegalovirus based simian
      immunodeficiency virus vaccine have identified strong CD8+ T cell responses that
      are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E
      restricted, have been identified. MHC-E therefore can present a wide range of
      epitope peptides to CD8+ T cells, alongside its well defined role in presenting a
      conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural
      killer cells. Here we explore the antigen processing pathways involved in these
      atypical T cell responses.

PMID- 28505605
TI  - Thickness and optical constants calculation for chalcogenide-alkali metal
      Se80Te8(NaCl)12 thin film.
AB  - Chalcogenide-alkali metal semiconducting thin films of four different thicknesses
      of Se80Te8(NaCl)12 are deposited from bulk by thermal evaporation technique. The
      crystallinity of the film improves with increasing of thickness as indicated by
      the recorded X-ray diffraction patterns. The transmission and reflection spectra
      are measured in the wavelength range of the incident photons from 250 to 2500nm.
      The thickness and optical constants of the films are calculated based on
      Swanepeol method using the interference patterns appeared in the transmission
      spectra. It is found that the films have absorption mechanism which is an
      indirect allowed transition. The effect of the film thickness on the refractive
      index and the high-frequency dielectric constant are studied. With increasing the
      film thickness, both the absorption coefficient and high-frequency dielectric
      constant increase while the single-oscillator energy, optical band gap and
      extinction coefficient decrease.

PMID- 28505604
TI  - Nrf2 and NF-kappaB modulation by Plumbagin attenuates functional, behavioural and
      biochemical deficits in rat model of neuropathic pain.
AB  - BACKGROUND: Plumbagin is known to exhibit a broad range of biological activities
      including anti-cancer, antimicrobial and has been widely used traditionally.
      Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kappaB)
      inhibitory and Nuclear factor (erythroid derived-2) like-2 (Nrf2) modulatory
      activities of Plumbagin have been reported already. In nerve injury model of
      neuropathy in rats, the role of NF-kappaB upregulation and declined antioxidant
      defence has been well recognized. So, we evaluated neuroprotective potential of
      Plumbagin in chronic constriction injury (CCI) of sciatic nerve induced
      neuropathic pain in male Sprague-Dawley rats. METHODS: Animals were tested for
      functional, behavioural and biochemical changes. Various markers associated with
      oxidative stress and inflammatory changes were assessed in the sciatic nerve and
      dorsal root ganglion (DRG) of the animals exposed to CCI mediated nerve injury.
      RESULTS: CCI induced nerve injury led to long-lasting mechanical hyperalgesia,
      loss of hind limb function and abnormal pain sensation. Plumbagin treatment (10
      and 20mg/kg, po) significantly and dose-dependently reversed mechanical
      hyperalgesia and other functional deficits. There was a marked increase in NF
      kappaB and reduced Nrf2 levels in sciatic nerve and DRG following nerve injury.
      Plumbagin strengthened the antioxidant defence by improving Nrf2 levels and
      checked the neuroinflammation by decreasing NF-kappaB levels in sciatic nerve and
      DRG. CONCLUSIONS: Together, these results suggested that Plumbagin alleviated CCI
      induced neuropathic pain via antioxidant and anti-inflammatory mechanisms. Hence,
      the study suggests that Plumbagin may be useful for the management of trauma
      induced neuropathic pain.

PMID- 28505606
TI  - A new azine derivative colorimetric and fluorescent dual-channel probe for
      cyanide detection.
AB  - A novel azine derivative colorimetric and fluorescent dual-channel probe
      salicylaldehyde hydrazine-3,5-dibromosalicylaldehyde (1) has been designed,
      synthesized and characterized. The probe 1 is confirmed to have especial
      selectivity and good sensitivity on detecting CN- via UV-vis absorption and
      fluorescence spectrum in aqueous solution (H2O/DMSO, 1:4, v/v). This colorimetric
      and fluorescent dual-channel probe response to CN- owed to the deprotonation
      process and established the mechanism by using 1H NMR spectroscopy. Further
      researches showed that the detection limit of the probe 1 to CN- anions is
      8.01*10-9M, significantly lower than the maximum level 1.9*10-6M in potable water
      from WHO guidelines.

PMID- 28505607
TI  - A flat acoustic lens to generate a Bessel-like beam.
AB  - We report a flat acoustic lens with a periodical structure to transform a
      divergent beam into a Bessel-like beam. Using the Schlieren imaging technique,
      the propagation process of acoustic wave in the periodical structure was
      experimentally observed. The pressure distribution in the main lobe is in good
      agreement with the Bessel function and the positions of the side lobes are close
      to the peak of the Bessel function. To observe the directivity of the beam,
      simulations were performed using the finite-element method. The simulation
      results indicated that the transmitted acoustic intensity at the central axis was
      several times greater with the lens than without it. The applicability of the
      lens for detecting the location of an acoustic source was also investigated.

PMID- 28505608
TI  - A differential optical interferometer for measuring short pulses of surface
      acoustic waves.
AB  - The measurement of the displacements caused by the propagation of a short pulse
      of surface acoustic waves on a solid substrate is investigated. A stabilized time
      domain differential interferometer is proposed, with the surface acoustic wave
      (SAW) sample placed outside the interferometer. Experiments are conducted with
      surface acoustic waves excited by a chirped interdigital transducer on a
      piezoelectric lithium niobate substrate having an operational bandwidth covering
      the 200-400MHz frequency range and producing 10-ns pulses with 36nm maximum out
      of-plane displacement. The interferometric response is compared with a direct
      electrical measurement obtained with a receiving wide bandwidth interdigital
      transducer and good correspondence is observed. The effects of varying the path
      difference of the interferometer and the measurement position on the surface are
      discussed. Pulse compression along the chirped interdigital transducer is
      observed experimentally.

PMID- 28505609
TI  - Disentanglement of Discordant Monochorionic Monoamniotic Twins in a Triplet
      Pregnancy: An Innovative Approach Utilizing Fetoscopic Laser Coagulation with
      Micro-Laparoscopic Scissor Dissection.

PMID- 28505610
TI  - Predictors of Loss to Follow-Up among Children with Type 2 Diabetes.
AB  - BACKGROUND/AIMS: Youth with type 2 diabetes (T2D) have poor compliance with
      medical care. This study aimed to determine which demographic and clinical
      factors differ between youth with T2D who receive care in a pediatric diabetes
      center versus youth lost to follow-up for >18 months. METHODS: Data were analyzed
      from 496 subjects in the Pe-diatric Diabetes Consortium registry. Enrollment
      variables were selected a priori and analyzed with univariable and multivariable
      logistic regression models. RESULTS: After a median of 1.3 years from enrollment,
      55% of patients were lost to follow-up. The final model included age,
      race/ethnicity, parent education, and estimated distance to study site. The odds
      ratio (99% confidence interval) of loss to follow-up was 2.87 (1.34, 6.16) for
      those aged 15 to <18 years versus those aged 10 to <13 years and 6.57 (2.67,
      16.15) for those aged >=18 years versus those aged 10 to <13 years. Among
      patients living more than 50 miles from the clinic, the odds ra tio of loss to
      follow-up was 3.11 (1.14, 8.49) versus those living within 5 miles of the site.
      CONCLUSION: Older adolescents with T2D are more likely to be lost to follow-up,
      but other socioeconomic factors were not significant predictors of clinic follow
      up.

PMID- 28505611
TI  - Novel Insights in Fetal Cardiomyopathy due to in utero Herpes Simplex Virus
      Infection.
AB  - This is a case report of fatal cardiomyopathy in a fetus following maternal
      intrauterine infection with herpes simplex virus (HSV), despite the mother having
      no symptoms of an infection. The fetus showed signs of a disseminated infection
      affecting the heart, brain, lungs, liver, adrenal glands, and skin. HSV
      cardiomyopathy, characterized by vast necrosis, extensive calcifications, and
      inflammatory infiltration, was found to be the cause of intrauterine fetal death.
      To our knowledge, this is a unique report of an asymptomatic maternal nonprimary
      or recurrent HSV infection that induced a transmission of HSV resulting in
      extensive and fatal changes in the fetal heart.

PMID- 28505612
TI  - Behavioral Performance and Neural Systems Are Robust to Sensory Injury in Workers
      of the Ant Pheidole dentata.
AB  - Miniaturized nervous systems have been thought to limit behavioral ability, and
      animals with miniaturized brains may be less flexible when challenged by injuries
      resulting in sensory deficits that impact the development, maintenance, and
      plasticity of small-scale neural networks. We experimentally examined how
      injuries to sensory structures critical for olfactory ability affect behavioral
      performance in workers of the ant Pheidole dentata, which have minute brains
      (0.01 mm3) and primarily rely on the perception and processing of chemical
      signals and cues to direct their social behavior. We employed unilateral antennal
      denervation to decrease the olfactory perception ability of workers and
      quantified consequential neuroanatomical and behavioral performance effects.
      Postablation neuroanatomical metrics revealed a 25% reduction in the volume of
      the antennal lobe ipsilateral to the antennal lesion relative to the
      contralateral lobe, indicating atrophy of the input-deprived tissue. However,
      antennectomy did not affect the volumes of the mushroom body or its
      subcompartments or the number of mushroom body synaptic complexes
      (microglomeruli) in either brain hemisphere. Synapsin immunoreactivity, however,
      was significantly higher in the ipsilateral mushroom body calyces, which could
      reflect presynaptic potentiation and homeostatic compensation in higher-order
      olfactory regions. Despite tissue loss caused by antennal lesioning and resulting
      unilateral sensory deprivation, the ability of workers to perform behaviors that
      encompass the breadth of their task repertoire and meet demands for colony labor
      remained largely intact. The few behavioral deficits recorded were restricted to
      pheromone trail-following ability, a result that was expected due to the need for
      bilateral olfactory input to process spatial odor information. Our macroscopic
      and cellular neuroanatomical measurements and assessments of task performance
      demonstrate that the miniaturized brains of P. dentata workers and their
      sensorimotor functions are remarkably robust to injury-related size reduction and
      remain capable of generating behaviors required to respond appropriately to
      chemical social signals and effectively nurse immatures, as well as participate
      in coordinated foraging.

PMID- 28505613
TI  - To Prime or Not to Prime - Is That Still a Question? A Comment on the US
      Guidelines on Growth Hormone and Insulin-Like Growth Factor-I Treatment in
      Children and Adolescents.

PMID- 28505614
TI  - Pulmonary Involvement in Adult Patients with Inborn Errors of Metabolism.
AB  - Inborn errors of metabolism (IEM) are rare individually, but taken together, they
      affect 1 in 1,000 people. Most of the disease becomes apparent at the pediatric
      age; however, with the identification of late-onset forms, and with improved
      survival, several of these conditions may be found in adults of all ages. While
      the lung is not typically a primary site of clinical disease in patients with
      IEM, in some of them it can be a significantly affected organ with associated
      severe respiratory complications. Lung involvement can be a late- onset feature
      of a complex multisystemic disease, but sometimes it can also be the only
      manifestation of underlying IEM. The aim of this review is to focus on specific
      IEM associated with lung disease in adults and to provide the reader with an
      overview of the diagnostic workup, overall disease management, and specific
      treatments for the respiratory manifestations. Clinical suspicion, early
      recognition, prompt diagnosis, and appropriate care of the respiratory
      manifestation are crucial, as they can affect both the life expectancy and the
      quality of life of these patients.

PMID- 28505615
TI  - Acute Disseminated Intravascular Coagulation after Oxaliplatin Infusion.
AB  - Oxaliplatin is one of the most commonly used drugs for patients with colorectal
      cancer. It has rarely been associated with disseminated intravascular coagulation
      (DIC) with only 3 previously reported cases. In all those instances, the patients
      had started receiving oxaliplatin, developed evidence of DIC during the course of
      planned treatment, and recovered with supportive care. We report a case of a 71
      year-old man with colorectal cancer treated successfully with an oxaliplatin
      based regimen who had disease relapse after 3 years. When treated again with
      oxaliplatin, he developed signs of an acute hypersensitivity reaction, and
      eventually had signs and symptoms consistent with DIC despite appropriate
      management. This case is unique in that a DIC reaction evolving from a
      hypersensitivity reaction occurred after the patient had already tolerated the
      drug years earlier. It suggests a possible immune-mediated etiology to this rare
      occurrence that should be kept in mind while utilizing this commonly employed
      drug.

PMID- 28505616
TI  - Pleural Biopsies: Just Freeze It?

PMID- 28505617
TI  - Ganglion Cell Complex in Early and Intermediate Age-Related Macular Degeneration:
      Evidence by SD-OCT Manual Segmentation.
AB  - PURPOSE: To evaluate ganglion cell layer (GCL) and ganglion cell complex (GCC)
      thickness manually by spectral-domain optical coherence tomography in subjects
      with early and intermediate age-related macular degeneration (AMD) in 12
      locations on the horizontal meridian. METHODS: A total of 450 eyes (specifically,
      246 eyes classified as having early/intermediate AMD plus 204 control eyes) were
      studied. Mann-Whitney U and Kruskal-Wallis tests were used to compare values
      between the healthy controls and the AMD group and also between the subgroups
      under study. Diagnostic performance was also compared calculating the areas under
      the receiver operating characteristic curve. RESULTS: The manual layer
      segmentation showed clear boundaries between the GCL and the GCC. It was in the
      temporal GCC that more changes were found. CONCLUSIONS: The GCC, especially in
      the temporal region, allowed the discrimination of differences between various
      subgroups that have faint variations as well as between early AMD and the first
      signs of aging.

PMID- 28505618
TI  - Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the
      Beijing Pharmacovigilance Database.
AB  - BACKGROUND: Few studies assessing the use of epinephrine in drug-induced
      anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing
      Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine
      for DIA management. METHODS: DIA cases collected in the BPD from January 2004 to
      December 2014 were adjudicated and analyzed for demographics, causative drugs,
      clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular
      adverse events (CAE) of epinephrine. RESULTS: DIA was primarily caused by
      antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine
      injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients
      received epinephrine treatment. Patients who received epinephrine were more
      likely to experience wheezing (p < 0.001) and respiratory arrest (p < 0.001).
      Among 518 patients with a complete record of the epinephrine administration
      route, the percentage of patients receiving it by intramuscular (IM) injection,
      subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous
      infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients
      with a record of both the administration route and the dosing, an overdose was
      more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; p < 0.001)
      or SC injection (43.7%; p < 0.001). Among the patients analyzed for CAE (n =
      349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were
      overdosed with epinephrine. CONCLUSION: Underuse, inappropriate IV bolus use, and
      overdosing were the 3 major problems with epinephrine use in DIA in China.
      Educational training for health care professionals on the appropriate use of
      epinephrine in managing anaphylactic reactions is suggested.

PMID- 28505620
TI  - Should Hidradenitis Suppurativa Be Included in Dermatoses Showing Koebnerization?
      Is It Friction or Fiction?
AB  - BACKGROUND: The etiology of hidradenitis suppurativa (HS) involves genetic and
      environmental factors. Well-established associated systemic factors are obesity,
      smoking, inflammation, and bacteria. Whether localized environmental factors such
      as friction and pressure may also play a causative role is still unclear.
      OBJECTIVE: To describe the possible Koebner phenomenon (KP) in HS. METHODS: The
      case notes on 14 patients with typical HS and additional HS lesions in previously
      uninvolved skin areas exposed to mechanical stress, e.g., on the abdomen at the
      level of the waistband, were reviewed with regard to the clinical characteristics
      of the cohort. RESULTS: All 14 patients (7 females) were obese with a mean BMI of
      35.8 (range 30.1-45.0). All patients developed additional ectopic HS lesions at
      the sites of friction on the convex abdomen. The ectopic lesions were clinically
      and histopathologically similar to HS. CONCLUSION: Mechanical stress factors or
      trauma play a role in obese patients with HS. It is suggested that these new
      induced lesions fit the concept of the KP. This phenomenon seems to occur in the
      so-called frictional furunculoid type of HS and may explain the unique
      distribution at certain localizations on the body of this follicular cutaneous
      eruption. Removal in an early stage of HS of external stress factors that can
      lead to the KP should be part of the treatment, especially in obese patients.

PMID- 28505619
TI  - Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via
      ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage.
AB  - BACKGROUND/AIMS: Intracerebral hemorrhage (ICH) occurs in hypertensive patients
      and results in high rates of mortality and disability. This study determined
      whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal
      regeneration and examined the underlying mechanisms after the administration of
      PD98059 (p-ERK1/2 inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis
      that was intended to be tested was that BMSC transplantation regulates the
      expression of growth-associated protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt
      signaling pathways. METHODS: Seventy-five male rats (250-280 g) were subjected to
      intracerebral blood injection and then randomly received a vehicle, BMSCs,
      PD98059 or LY294002 treatment. Neurological deficits were evaluated prior to
      injury and at 1, 3 and 7 days post-injury. The expression of GAP-43, Akt, p-Akt,
      ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis. RESULTS:
      BMSC transplantation attenuated neurological deficits 3-7 days post-ICH. The
      expression of GAP-43 was increased 3 days following BMSC transplantation.
      However, this increase was inhibited by either PD98059 or LY294002 treatment.
      Treatment with both PD98059 and LY294002 was more effective than was treatment
      with an individual compound. CONCLUSION: BMSC transplantation could attenuate
      neurological deficits and activate axonal regeneration in this rat ICH model. The
      protective effects might be associated with increased GAP-43 expression by
      activating both the ERK1/2 and PI3K/Akt signaling pathways.

PMID- 28505621
TI  - GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of
      the HPG Axis and Fertility.
AB  - The gonadotropin-releasing hormone agonist (GnRHa; Buserelin) rescues fertility
      during adulthood in the majority of high infertility risk cryptorchid boys
      presenting with defective mini-puberty. However, the molecular events governing
      this effect are not understood. We report the outcome of an RNA profiling
      analysis of testicular biopsies from 4 operated patients who were treated with
      GnRHa for 6 months versus 3 operated controls who were not treated. GnRHa induces
      a significant transcriptional response, including protein-coding genes involved
      in pituitary development, the hypothalamic-pituitary-gonadal axis, and
      testosterone synthesis. Furthermore, we observed an increased abundance of long
      noncoding RNAs (lncRNAs) participating in epigenetic processes, including AIRN,
      FENDRR, XIST, and HOTAIR. These data are consistent with the hypothesis that
      hypogonadotropic hypogonadism in boys with altered mini-puberty is the
      consequence of a profoundly altered gene expression program involving protein
      coding genes and lncRNAs. Our results point to molecular mechanisms that underlie
      the ability of GnRHa to rescue fertility.

PMID- 28505623
TI  - Effect of a Low-Rank Denoising Algorithm on Quantitative Magnetic Resonance
      Imaging-Based Measures of Liver Fat and Iron.
AB  - PURPOSE: This study aimed to assess the effect of a low-rank denoising algorithm
      on quantitative magnetic resonance imaging-based measures of liver fat and iron.
      MATERIALS AND METHODS: This was an institutional review board-approved, Health
      Insurance Portability and Accountability Act-compliant, retrospective analysis of
      42 consecutive subjects who were imaged at 3T using a multiecho gradient echo
      sequence that was reconstructed using the multistep adaptive fitting algorithm to
      obtain quantitative proton density fat fraction (PDFF) and R2* maps (original
      maps). A patch-wise low-rank denoising algorithm was then applied, and PDFF and
      R2* maps were created (denoised maps). Three readers independently rated the PDFF
      maps in terms of vessel and liver edge sharpness and image noise using a 5-point
      scale. Two other readers independently measured mean and standard deviation of
      PDFF and R2* values for the original and denoised maps; values were compared
      using intraclass correlation coefficients (ICCs) and mean difference analyses.
      RESULTS: Qualitatively, the denoised maps were preferred by all 3 readers based
      on image noise (P < 0.001) and by 2 of 3 readers based on vessel edge sharpness
      (P < 0.001-0.99). No reader had a significant preference regarding liver edge
      sharpness (P = 0.16-0.48). Quantitatively, agreement was near perfect between the
      original and denoised maps for PDFF (ICC = 0.995) and R2* (ICC = 0.995) values.
      Mean quantitative values obtained from the original and denoised maps were
      similar for liver PDFF (7.6 +/- 7.7% vs 7.7 +/- 7.8%; P = 0.63) and R2* (52.9 +/-
      40.3s vs 52.8 +/- 41.1 s, P = 0.74). CONCLUSIONS: Applying the low-rank denoising
      algorithm to liver fat and iron quantification reduces image noise in PDFF and
      R2* maps without adversely affecting mean quantitative values or subjective image
      quality.

PMID- 28505624
TI  - Spectral Computed Tomography Imaging of Gastric Schwannoma and Gastric Stromal
      Tumor.
AB  - : Gastric schwannomas (GSs) and gastrointestinal stromal tumors (GSTs) are
      grossly similar submucosal neoplasms with different prognoses. We explored the
      value of spectral computed tomography (CT) to distinguish between them. METHODS:
      Patients diagnosed with GS or GST at Lanzhou University Second Hospital, China,
      between May 2013 and June 2015 were included retrospectively. The subjects
      underwent spectral CT examination before surgery and had histologically confirmed
      diagnosis of GS or GST. RESULTS: Twelve patients with GS (3 men; 9 women; mean
      [SD] age, 47.0 [11.5] years) and 20 with GST (7 men; 13 women; mean [SD] age,
      54.7 [9.9]) showed significant differences in terms of arterial phase (AP) at 70
      keV (P < 0.001), portal phase (PP) at 70 keV (P = 0.002), AP iodine
      concentration, PP iodine concentration, AP water concentration, AP slope of
      spectral curve, and PP slope of spectral curve (all P < 0.001). CONCLUSIONS:
      Spectral CT may be useful for noninvasive diagnosis of submucosal tumors.

PMID- 28505622
TI  - Fat Suppressed Contrast-Enhanced T1-Weighted Dynamic Magnetic Resonance Imaging
      at 3T: Comparison of Image Quality Between Spectrally Adiabatic Iversion Recovery
      and the Multiecho Dixon Technique in Imaging of the Prostate.
AB  - OBJECTIVE: To compare the quality of fat suppression and image quality between
      multiecho Dixon technique (mDixon) and spectrally adiabatic iversion recovery
      (SPAIR) in dynamic contrast-enhanced magnetic resonance imaging of the prostate.
      METHODS: This prospective study assigned thirty consecutive patients to scanning
      with SPAIR technique (SPAIR protocol) and another consecutive 30 patients to
      scanning with mDixon technique (mDixon protocol). We calculated the contrast,
      signal to noise ratio (SNR), contrast to noise ratio (CNR) and the coefficient of
      variation between the 2 protocols. Two readers compared homogeneity of fat
      suppression, image noise, image contrast, and image sharpness between the two
      protocols. RESULTS: The SNR, CNR, and contrast of mDixon protocol were
      significantly higher than those of the SPAIR protocol (SNR: 14.7 +/- 4.1 vs 11.0
      +/- 2.6; P < 0.05; CNR: 6.3 +/- 1.6 vs 0.5 +/- 1.5; P < 0.01; contrast: 4.4 +/-
      1.4 vs 1.3 +/- 0.5; P < 0.01), whereas the coefficient of variation of mDixon
      protocol was significantly lower than that of SPAIR protocol (34.7 +/- 15.5 vs
      43.7 +/- 23.1, P < 0.01). In qualitative image analysis, the image scores for the
      homogeneity of fat suppression, image noise, and image sharpness were
      significantly higher with mDixon protocol than those with SPAIR protocol (P <
      0.01). There was no significant difference in image contrast between 2 fat
      suppression protocols (P > 0.05). CONCLUSIONS: In dynamic contrast-enhanced
      magnetic resonance imaging of the prostate, mDixon technique improved the
      homogeneity of fat suppression without degrade of image quality compared with
      SPAIR technique.

PMID- 28505625
TI  - Metal Artifact Reduction on Chest Computed Tomography Examinations: Comparison of
      the Iterative Metallic Artefact Reduction Algorithm and the Monoenergetic
      Approach.
AB  - OBJECTIVE: The aim of the study was to compare iterative metallic artefact
      reduction (iMAR) and monochromatic imaging on metal artifact reduction. MATERIALS
      AND METHODS: Follow-up of 29 occluded pulmonary arteriovenous malformations was
      obtained with dual-energy computed tomography with reconstruction of averaged
      images using filtered back projection (group 1), iMAR (group 2), and creation of
      high-energy monoenergetic images (group 3). Two types of coils had been used: (a)
      nickel only (group A, n = 18) and (b) nickel and platinum (group B, n = 11).
      RESULTS: Compared with group 1, groups 2 and 3 images showed significant
      reduction in artifact severity. Compared with group 3, group 2 images showed less
      artifacts on subjective (artifact severity score: P = 0.0118; score of visibility
      of surrounding structures: P = 0.0056) and objective (artifact attenuation: P <
      0.0001) analyses. In group A, there was no significant difference in artifact
      severity between groups 2 and 3 images (P > 0.05). In group B, metal artifacts
      were only significantly reduced in group 2 images. CONCLUSIONS: Iterative
      metallic artefact reduction reduces metal artifacts more efficiently than
      monoenergetic imaging.

PMID- 28505626
TI  - Discrimination Between Patients With Alzheimer Disease and Healthy Subjects Using
      Layer Analysis of Cerebral Blood Flow and Xenon Solubility Coefficient in Xenon
      Enhanced Computed Tomography.
AB  - OBJECTIVE: The aim of this study was to develop a method for discriminating
      between patients with Alzheimer disease (AD) and healthy subjects using layer
      analysis of cerebral blood flow (CBF) and xenon solubility coefficient (lambda)
      in xenon-enhanced computed tomography (CT). METHODS: Xenon-enhanced CT was
      performed on 27 patients with AD (81.7 [3.3] years old) and 15 healthy volunteers
      (78.6 [4.0] years old) using a wide volume CT. For each subject, we created the
      first- (surface) to sixth-layer images of CBF and lambda for the 6 viewing
      directions (layer thickness, 5 mm). For the discriminant views, receiver
      operating characteristic curves for the ratio of CBF to lambda were created to
      identify patients with AD. RESULTS: For the third- and fourth-layer left lateral
      views, which were designated as the discriminant views, areas under the receiver
      operating characteristic curve were 96.8% and 97.4%, respectively. CONCLUSIONS:
      With the use of the discriminant views obtained by xenon-enhanced CT, we could
      effectively discriminate between patients with AD and healthy subjects using both
      CBF and lambda.

PMID- 28505627
TI  - Endothelial Damage Signals Refractory Acute Kidney Injury in Critically Ill
      Patients.
AB  - : Critically ill patients with acute kidney injury (AKI) are heterogeneous on
      pathophysiology and prognosis. The role of endothelial damage in the pathogenesis
      of refractory AKI has not been clarified. The aim was to determine if biomarkers
      of endothelial damage, independently of the inflammatory insult on the kidney,
      can predict recovery of acute kidney injury. METHODS: From the "Procalcitonin And
      Survival Study" multicenter intensive care unit cohort, followed for 28 days
      after admission, we included patients without chronic kidney disease, who
      survived >24 h after admission and with plasma samples at admission available for
      biomarker analysis. We defined AKI by the "Kidney Disease: Improving Global
      Outcomes" guidelines and recovery of prior kidney function as alive for five
      consecutive days after admission with no need for renal replacement therapy and
      creatinine levels consistently below *1.5 the level before admission. We adjusted
      models for age, gender, vasopressor treatment, mechanical ventilation and levels
      of creatinine, procalcitonin, platelets, and bilirubin at admission. RESULTS: Of
      a total 213 with AKI at admission, 99 recovered prior kidney function during
      follow-up. Endothelial damage on admission, measured by Soluble Thrombomodulin
      (sTM), was the strongest predictor of a reduced chance of recovery of prior
      kidney function (sTM in the highest vs. three lower quartiles hazard ratio 0.39;
      95% confidence interval 0.21-0.73, P = 0.003). In contrast, the degree of the
      initial inflammatory insult on the kidney, measured by neutrophil gelatinase
      associated lipocalin (NGAL), failed to predict this outcome (NGAL in highest vs.
      three lower quartiles hazard ratio = 1.20; 95% CI 0.72-2.00; P = 0.48).
      Procalcitonin, a specific marker of bacterial infection, was also associated with
      the rate of recovery (PCT in highest vs. three lower quartiles hazard ratio =
      0.59; 95% CI 0.36-0.98; P = 0.04). CONCLUSION: AKI patients with high levels of
      sTM had a reduced chance of recovering prior renal function. Our findings support
      disintegration of the endothelium as a critical point in the pathogenesis of AKI
      that is refractory to treatment.

PMID- 28505628
TI  - Markers of Intestinal Damage and their Relation to Cytokine Levels in Cardiac
      Surgery Patients.
AB  - OBJECTIVES: In patients undergoing cardiac surgery, both extracorporeal
      circulation (ECC) and intraoperative mesenterial hypoperfusion may account for
      increased cytokine levels and lead to postoperative gastrointestinal (GI)
      symptoms. METHODS: We investigated levels of the intestinal damage markers
      intestinal fatty acid binding protein (I-FABP in plasma [n = 72] and urine [n =
      37]), citrulline (in plasma [n = 35]), and claudin-3 (in urine [n = 37]) in
      patients undergoing aortic or mitral valve surgery with or without coronary
      artery bypass grafting. Furthermore, the relationship between these markers and
      the surgery-induced cytokine response was explored by measuring serial plasma
      levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 (n =
      35). Finally, the relationship between markers of intestinal damage and GI
      symptoms (abdominal pain, ileus, vomiting, diarrhea, time to first defecation)
      was assessed. RESULTS: Plasma and urinary I-FABP levels, and urinary claudin-3
      levels peaked at the end of surgery, while citrulline levels were not influenced
      by surgery. ECC duration correlated with plasma I-FABP levels (r = 0.31, P =
      0.007). Plasma levels of all measured cytokines increased during surgery, with
      peak levels observed either at the end of surgery or on the first postoperative
      day. While ECC duration correlated with IL-6 and IL-8 release (r = 0.43, P = 0.01
      and r = 0.36, P = 0.04 respectively), there was no direct relationship between I
      FABP and claudin-3 levels and cytokine concentrations. No patients developed
      significant GI or non-GI complications, and I-FABP and claudin-3 release appeared
      not to be related to postoperative GI symptoms, although the incidence of these
      symptoms may have limited a reliable assessment. CONCLUSIONS: Longer duration of
      ECC is associated with a more pronounced release of intestinal injury markers and
      inflammatory cytokines, but intestinal injury markers are not directly related to
      the observed increase in cytokine levels or GI-symptoms. These findings indicate
      that ECC duration contributes to the cytokine response observed in cardiac
      surgery patients and that intestinal injury itself is not a causative factor for
      this response.

PMID- 28505630
TI  - MACRA: Big Fix or Big Problem?

PMID- 28505629
TI  - Impacts and mitigation of excess diesel-related NOx emissions in 11 major vehicle
      markets.
AB  - Vehicle emissions contribute to fine particulate matter (PM2.5) and tropospheric
      ozone air pollution, affecting human health, crop yields and climate worldwide.
      On-road diesel vehicles produce approximately 20 per cent of global anthropogenic
      emissions of nitrogen oxides (NOx), which are key PM2.5 and ozone precursors.
      Regulated NOx emission limits in leading markets have been progressively
      tightened, but current diesel vehicles emit far more NOx under real-world
      operating conditions than during laboratory certification testing. Here we show
      that across 11 markets, representing approximately 80 per cent of global diesel
      vehicle sales, nearly one-third of on-road heavy-duty diesel vehicle emissions
      and over half of on-road light-duty diesel vehicle emissions are in excess of
      certification limits. These excess emissions (totalling 4.6 million tons) are
      associated with about 38,000 PM2.5- and ozone-related premature deaths globally
      in 2015, including about 10 per cent of all ozone-related premature deaths in the
      28 European Union member states. Heavy-duty vehicles are the dominant contributor
      to excess diesel NOx emissions and associated health impacts in almost all
      regions. Adopting and enforcing next-generation standards (more stringent than
      Euro 6/VI) could nearly eliminate real-world diesel-related NOx emissions in
      these markets, avoiding approximately 174,000 global PM2.5- and ozone-related
      premature deaths in 2040. Most of these benefits can be achieved by implementing
      Euro VI standards where they have not yet been adopted for heavy-duty vehicles.

PMID- 28505631
TI  - Cholesterol Evaluation in Young Adults: Absence of Clinical Trial Evidence Is Not
      a Reason to Delay Screening.

PMID- 28505633
TI  - Prevalence of Elevated Cardiovascular Risks in Young Adults.

PMID- 28505634
TI  - Guideline: Insufficient evidence exists on screening for obstructive sleep apnea
      in asymptomatic adults.

PMID- 28505632
TI  - Missed Opportunities for Measles, Mumps, Rubella Vaccination Among Departing U.S.
      Adult Travelers Receiving Pretravel Health Consultations.
AB  - Background: Measles outbreaks continue to occur in the United States and are
      mostly due to infections in returning travelers. Objective: To describe how
      providers assessed the measles immunity status of departing U.S. adult travelers
      seeking pretravel consultation and to assess reasons given for nonvaccination
      among those considered eligible to receive the measles, mumps, rubella (MMR)
      vaccine. Design: Observational study in U.S. pretravel clinics. Setting: 24 sites
      associated with Global TravEpiNet (GTEN), a Centers for Disease Control and
      Prevention-funded consortium. Patients: Adults (born in or after 1957) attending
      pretravel consultations at GTEN sites (2009 to 2014). Measurements: Structured
      questionnaire completed by traveler and provider during pretravel consultation.
      Results: 40 810 adult travelers were included; providers considered 6612 (16%) to
      be eligible for MMR vaccine at the time of pretravel consultation. Of the MMR
      eligible, 3477 (53%) were not vaccinated at the visit; of these, 1689 (48%) were
      not vaccinated because of traveler refusal, 966 (28%) because of provider
      decision, and 822 (24%) because of health systems barriers. Most MMR-eligible
      travelers who were not vaccinated were evaluated in the South (2262 travelers
      [65%]) or at nonacademic centers (1777 travelers [51%]). Nonvaccination due to
      traveler refusal was most frequent in the South (1432 travelers [63%]) and in
      nonacademic centers (1178 travelers [66%]). Limitation: These estimates could
      underrepresent the opportunities for MMR vaccination because providers accepted
      verbal histories of disease and vaccination as evidence of immunity. Conclusion:
      Of U.S. adult travelers who presented for pretravel consultation at GTEN sites,
      16% met criteria for MMR vaccination according to the provider's assessment, but
      fewer than half of these travelers were vaccinated. An increase in MMR
      vaccination of eligible U.S. adult travelers could reduce the likelihood of
      importation and transmission of measles virus. Primary Funding Source: Centers
      for Disease Control and Prevention, National Institutes of Health, and the Steve
      and Deborah Gorlin MGH Research Scholars Award.

PMID- 28505635
TI  - Review: In children and adults, vitamin D3 supplementation reduces risk for acute
      respiratory tract infection.

PMID- 28505636
TI  - Review: In COPD, injectable polyvalent pneumococcal vaccines reduce risk for
      community-acquired pneumonia.

PMID- 28505637
TI  - In C difficile infection, adding IV bezlotoxumab to standard antibiotics reduced
      recurrence at 12 weeks.

PMID- 28505638
TI  - Review: After coronary DES, <= 6 mo and 1 y of dual-antiplatelet therapy do not
      differ for CV events at 1 y.

PMID- 28505639
TI  - Review: Targeting SBP lowering to < 140 mm Hg reduces MACE more than targeting
      SBP to > 140 in hypertensive patients >= 65 y.

PMID- 28505640
TI  - In older men with low testosterone levels and age-associated memory impairment,
      testosterone did not improve memory.

PMID- 28505641
TI  - Bariatric surgery improved HbA1c at 5 y more than intensive medical care alone in
      obese patients with T2DM.

PMID- 28505642
TI  - Review: Strategies to improve provider adoption and implementation of clinical
      practice guidelines were assessed.

PMID- 28505643
TI  - Review: Interventions improve hospital antibiotic prescribing and reduce hospital
      stay but do not affect mortality.

PMID- 28505645
TI  - Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries
      Aged 70 to 79 Years.

PMID- 28505646
TI  - Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries
      Aged 70 to 79 Years.

PMID- 28505647
TI  - Management of Acute and Recurrent Gout.

PMID- 28505648
TI  - Management of Acute and Recurrent Gout.

PMID- 28505649
TI  - Management of Acute and Recurrent Gout.

PMID- 28505650
TI  - Patient-Centered Medical Homes and Adherence to Chronic Disease Medications.

PMID- 28505651
TI  - Patient-Centered Medical Homes and Adherence to Chronic Disease Medications.

PMID- 28505652
TI  - This Is Why.

PMID- 28505653
TI  - Forbidden Topics.

PMID- 28505654
TI  - The Clearing.

PMID- 28505655
TI  - Leg Braces, Bronzed, in a Dusty Box.

PMID- 28505657
TI  - Web Exclusives. Annals for Hospitalists Inpatient Notes - Predicting Codes-A
      Future With Fewer In-Hospital Cardiac Arrests.

PMID- 28505658
TI  - Web Exclusives. Annals Consult Guys - The Adult Survivor of Hodgkin Disease:
      Falling Through the Cracks.

PMID- 28505661
TI  - Why Aren't International Travelers Vaccinated for Measles?

PMID- 28505660
TI  - Prevalence of Elevated Cardiovascular Risks in Young Adults: A Cross-sectional
      Analysis of National Health and Nutrition Examination Surveys.
AB  - Background: The 2013 cholesterol management guidelines from the American College
      of Cardiology and American Heart Association (ACC/AHA) recommend lipid screening
      in all adults older than 20 years to identify those at increased risk for
      atherosclerotic cardiovascular disease (ASCVD). Statins may be considered for
      patients with elevated 10-year risk (>5%) or a low-density lipoprotein
      cholesterol (LDL-C) level of 4.92 mmol/L (190 mg/dL) or greater. Objective: To
      describe the prevalence of elevated ASCVD risk among nondiabetic adults younger
      than 50 years. Design: Cross-sectional. Setting: NHANES (National Health and
      Nutrition Examination Survey), 1999 to 2000 through 2011 to 2012. Participants:
      Adults aged 30 to 49 years without known ASCVD or diabetes. Measurements: 10-year
      ASCVD risk was estimated by using the 2013 ACC/AHA ASCVD risk calculator.
      Participants were subdivided by age, sex, and history of smoking and
      hypertension. The percentages of adults in each subgroup with a 10-year ASCVD
      risk greater than 5% and of those with an LDL-C level of 4.92 mmol/L (190 mg/dL)
      or greater were estimated. Low-prevalence subgroups were defined as those in
      which a greater than 1% prevalence of elevated cardiovascular risk could be ruled
      out (that is, the upper 95% confidence bound for prevalence was <=1%). Results:
      Overall, 9608 NHANES participants representing 67.9 million adults were included,
      with approximately half (47.12%, representing 32 million adults) in low
      prevalence subgroups. In the absence of smoking or hypertension, 0.09% (95% CI,
      0.02% to 0.35%) of adult men younger than 40 years and 0.04% (CI, 0.0% to 0.26%)
      of adult women younger than 50 years had an elevated risk. Among other subgroups,
      0% to 75.9% of participants had an increased risk. Overall, 2.9% (CI, 2.3% to
      3.5%) had an LDL-C level of 4.92 mmol/L (190 mg/dL) or greater. Limitation: No
      information was available regarding cardiovascular outcomes. Conclusion: In the
      absence of risk factors, the prevalence of increased ASCVD risk is low among
      women younger than 50 and men younger than 40 years. Primary Funding Source:
      None.

PMID- 28505662
TI  - Asymmetries between convergence and divergence reveal tonic vergence is dependent
      upon phasic vergence function.
AB  - Horizontal vergence eye movements are controlled by two processes, phasic and
      slow-tonic. Slow-tonic responses are hypothesized to be stimulated by the faster,
      pulse-step neural output of the phasic system. This suggests that the general
      behavior of each system should be similar; however, this relationship has yet to
      be investigated directly. We characterize the relationship between phasic and
      tonic vergence by quantifying directional asymmetries in the response properties
      of each mechanism to the same disparity amplitudes. Four subjects viewed
      symmetric steps in disparity dichoptically at 40 cm while eye movements were
      recorded with infrared oculography. First- and second-order phasic and slow-tonic
      convergence response properties increased linearly with disparity demand (p <
      0.01), whereas divergence responses did not (p > 0.05). Phasic divergence
      responses were slower than convergence (p = 0.012) and were associated with a
      higher frequency of saccades (p < 0.001). The average rate of slow-tonic change
      was correlated to the average peak velocity of phasic vergence at the same
      vergence demand in both directions, r = 0.78, p < 0.0001. Clear directional
      asymmetries were observed in phasic and tonic vergence responses. The response
      properties of the slow-tonic mechanism varied directly with the peak velocity of
      the complementary phasic system. These results provide empirical evidence of the
      relationship between phasic and slow-tonic vergence, suggesting that the latter
      depends on the motor function of the former, specifically the peak velocity. The
      recruitment of additional oculomotor mechanisms, such as saccades, improved the
      phasic response properties of the slower divergence mechanism but did not
      directly influence the response behavior of the slow-tonic mechanism.

PMID- 28505663
TI  - Possible role for recurrent interactions between expansion and contraction cells
      in MSTd during self-motion perception in dynamic environments.
AB  - Cortical area MSTd contains cells sensitive to the radial expansion and
      contraction motion patterns experienced during forward and backward self-motion.
      We investigated the open question of whether populations of MSTd cells tuned to
      expansion and contraction interact through recurrent connectivity, which may play
      important roles in postural control and resolving heading in dynamic
      environments. We used a neural model of MSTd to generate predictions about the
      consequences of different types of interactions among MSTd expansion and
      contraction cells for heading signals produced in the case of self-motion in the
      presence of a retreating object-a stimulus that recruits both expansion and
      contraction MSTd cell populations. Human heading judgments from a psychophysical
      experiment that we conducted were consistent only with the MSTd model that
      contained recurrent connectivity within and between expansion and contraction
      cell populations. The model and human heading judgments were biased in the
      direction of the object motion when the object crossed the observer's future path
      and biased in the opposite direction when the object did not cross the path. We
      conclude that recurrent interactions among expansion and contraction cells in
      MSTd provide a plausible mechanism to support robust self-motion through dynamic
      environments.

PMID- 28505664
TI  - Temporal brightness illusion changes color perception of "the dress".
AB  - "The dress" has provoked intensive commentary among psychophysicists, especially
      in relation to color vision. Researchers have shown that manipulating illuminance
      cues can influence the perceived colors of the dress. Here we investigate whether
      illusory shifts in brightness can shift color perception of the dress. Drifting
      achromatic gratings with fast off and fast on shading profiles are known to give
      an illusion of brightening or darkening, respectively. We superimposed rotating
      sawtooth gratings on a series of dress images that morphed from extreme
      white/gold through to blue/black. In a sample of 18 adults (11 with white/gold
      dress percept and seven with blue/black percept), a two-alternative, forced
      choice constant stimulus task measured the morphed image point at which each
      observer was equally likely to categorize the dress as white/gold or blue/black
      (the point of subjective equality or PSE). Despite manifest individual
      differences in the PSE, the two sawtooth temporal profiles consistently changed
      the perceived colors of the dress. Perceptual dimming shifted color
      categorization toward blue/black whereas perceptual brightening shifted color
      categorization toward white/gold. We conclude that color categorization is
      influenced substantially by illusory shifts in brightness.

PMID- 28505665
TI  - Visual wetness perception based on image color statistics.
AB  - Color vision provides humans and animals with the abilities to discriminate
      colors based on the wavelength composition of light and to determine the location
      and identity of objects of interest in cluttered scenes (e.g., ripe fruit among
      foliage). However, we argue that color vision can inform us about much more than
      color alone. Since a trichromatic image carries more information about the
      optical properties of a scene than a monochromatic image does, color can help us
      recognize complex material qualities. Here we show that human vision uses color
      statistics of an image for the perception of an ecologically important surface
      condition (i.e., wetness). Psychophysical experiments showed that overall
      enhancement of chromatic saturation, combined with a luminance tone change that
      increases the darkness and glossiness of the image, tended to make dry scenes
      look wetter. Theoretical analysis along with image analysis of real objects
      indicated that our image transformation, which we call the wetness enhancing
      transformation, is consistent with actual optical changes produced by surface
      wetting. Furthermore, we found that the wetness enhancing transformation operator
      was more effective for the images with many colors (large hue entropy) than for
      those with few colors (small hue entropy). The hue entropy may be used to
      separate surface wetness from other surface states having similar optical
      properties. While surface wetness and surface color might seem to be independent,
      there are higher order color statistics that can influence wetness judgments, in
      accord with the ecological statistics. The present findings indicate that the
      visual system uses color image statistics in an elegant way to help estimate the
      complex physical status of a scene.

PMID- 28505666
TI  - Acute Pancreatitis: How Soon Should We Feed Patients?

PMID- 28505667
TI  - Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic
      Review.
AB  - Background: Acute pancreatitis is among the most common and costly reasons for
      hospitalization in the United States. Bowel rest, pain control, and intravenous
      fluids are the cornerstones of treatment, but early feeding might also be
      beneficial. Purpose: To compare length of hospital stay, mortality, and
      readmission in adults hospitalized with pancreatitis who received early versus
      delayed feeding. Data Sources: MEDLINE via Ovid, EMBASE, the Cochrane Library,
      CINAHL, and Web of Science through January 2017. Study Selection: Two authors
      independently reviewed and selected studies if they were randomized clinical
      trials, included adults hospitalized with acute pancreatitis, and compared early
      versus delayed feeding (<=48 vs. >48 hours after hospitalization). Data
      Extraction: Two investigators independently extracted study data and rated risk
      of bias using the Cochrane Collaboration tool. Data Synthesis: Eleven randomized
      trials (8 peer-reviewed publications, 3 abstract-only presentations) that
      included 948 patients were eligible. Seven trials (3 with low risk of bias)
      enrolled patients with mild to moderate pancreatitis. Four trials (1 with low
      risk of bias) included patients with predicted severe pancreatitis. Routes used
      for early feeding included oral (4 studies), nasogastric (2 studies), nasojejunal
      (4 studies), and oral or nasoenteric (1 study). Among patients with mild to
      moderate pancreatitis, early feeding was associated with reduced length of stay
      in 4 of 7 studies (including 2 of 3 with low risk of bias). Other outcomes were
      heterogeneous and variably reported, but no study showed an increase in adverse
      events with early feeding. Among patients with severe pancreatitis, limited
      evidence revealed no statistically significant difference in outcomes between
      early and delayed feeding. Limitation: Heterogeneity of feeding protocols and
      outcomes, scant data, and unclear or high risk of bias in several studies.
      Conclusion: Limited data suggest that early feeding in patients with acute
      pancreatitis does not seem to increase adverse events and, for patients with mild
      to moderate pancreatitis, may reduce length of hospital stay. Primary Funding
      Source: None. (PROSPERO: CRD42015016193).

PMID- 28505668
TI  - Postmalaria Neurologic Syndrome-Autoimmune Encephalitis With Anti-Voltage-Gated
      Potassium-Channel Antibodies.

PMID- 28505670
TI  - The Increasing Genetic and Phenotypical Diversity of Congenital Myasthenic
      Syndromes.

PMID- 28505671
TI  - MEGDEL Syndrome: Expanding the Phenotype and New Mutations.

PMID- 28505672
TI  - ["Translational Research in Ophthalmology is Important!"]

PMID- 28505669
TI  - Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum
      Disorder - When, Who, and How?
AB  - The aim of this study was to evaluate antidepressant add-on treatment within the
      acute treatment of schizophrenia spectrum disorder patients. Antidepressant add
      on was evaluated in 365 patients within a naturalistic multicenter study.
      Patients with/without antidepressant add-on were compared regarding clinical and
      treatment-related variables, response and remission, and remission of depressive
      and negative symptoms. The efficacy of antidepressant add-on treatment was
      furthermore analyzed applying marginal structure models. Twenty-three percent of
      the patients received antidepressant add-on for a mean duration of 50.28 (33.42)
      days. Patients with the diagnosis of a schizoaffective disorder, multiple illness
      episodes, and a longer duration of their illness as well as those with
      significantly fewer baseline positive symptoms, more negative and depressive
      symptoms, more side effects, and less subjective well-being were augmented with
      antidepressants. At discharge no significant effect of antidepressant add-on
      treatment was observed in terms of a 25% improvement (p=0.2623), a 50%
      improvement (p=0.3946), remission (p=0.0552), or remission of depressive
      (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal
      structure models considering the diagnostic subgroups, no significant effect was
      found. Add-on with antidepressants is common. A final recommendation in terms of
      this strategy's efficacy cannot be given.

PMID- 28505673
TI  - [HLA-B27 Positive Acute Anterior Uveitis - A Translational Perspective].
AB  - Background HLA-B27 positive acute anterior uveitis is the most common type of
      uveitis, and it is an autoimmune disease that can be triggered by infections. The
      precise mechanism of the interaction between involved microbes (mostly gram
      negative bacteria) and the host immune system is not clear. The disease probably
      results from an imbalance between pro- and anti-inflammatory components. Project
      description This article gives a compact overview about the current knowledge of
      the clinic and the etiopathogenesis of acute anterior uveitis as a basis for
      future research approaches. The goal of the current research is to classify the
      cellular and molecular pathogenetic factors in acute anterior uveitis. In this
      regard, a project on uveitis within the clinical research unit FOR 2240
      "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye",
      examines the hypothesis that dysregulation of regulatory cell populations and
      anti-inflammatory cytokines, such as interleukin-10 (IL-10), might contribute to
      the development of ocular autoimmunity following infections. The goal is to
      establish new markers for individual susceptibility in the risk group of the HLA
      B27 positive population, because only about 1% of the HLA-B27 positive population
      will eventually develop acute anterior uveitis. Conclusions Translational
      research approaches to identify predisposed risk groups from the HLA-B27
      population could improve patient care both on a prophylactic and a therapeutic
      level.

PMID- 28505674
TI  - [Novel Adjuvant Therapy for Ocular Melanoma].
AB  - Background Malignant melanoma is the most common cancer of the eye in adults that
      originates either in the intra-ocular uveal tract or extra-ocular conjunctiva.
      Although the primary tumor can be treated successfully, no effective therapy for
      both metastatic conjunctival and uveal melanoma currently exits. Tumor-associated
      lymphangiogenesis and immune cell infiltration play a pivotal role in the
      development and therapeutic targeting of metastases. Project description Here, we
      provide an overview of current translational research on lymphangiogenesis and
      its therapeutic inhibition as well as modulation of immune cell infiltration by
      passive and active immunotherapy in melanoma of the eye. Specifically, our
      previous and ongoing work on lymphangiogenesis and immune cells in ocular
      melanoma within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and
      Cellular Immunity in Inflammatory Diseases of the Eye" is summarized. Conclusions
      Translational research on the modulation of tumor-associated lymphangiogenesis
      and immune cell infiltration could provide novel targets for adjuvant therapy in
      melanoma of the eye.

PMID- 28505675
TI  - [Anti(lymph)angiogenic Strategies to Improve Corneal Graft Survival].
AB  - Corneal transplantation (keratoplasty) is the most frequently performed form of
      transplantation worldwide. A rejection reaction against the transplant is the
      main complication occurring after transplantation in an already vascularized, so
      called "high-risk" recipient eye. Our group has shown that clinically invisible
      lymphatic vessels play a crucial role in the induction of a rejection reaction
      against the corneal graft, and that anti-(lymph)angiogenic therapies in the mouse
      model of keratoplasty can significantly improve transplant survival. The
      underlying mechanisms, which improve transplant survival through anti
      lymphangiogenic therapies have not been well understood. We assume that the
      blockade of lymph vessel sprouting leads to a tolerance (and not to a simple
      ignorance) of the transplant, in which the antigen-presenting cells are held
      longer in the cornea and, thus, an immunomodulation of these cells occurs.
      Therefore, an important goal of our project is to find out whether and when
      transplant tolerance comes from a corneal anti-lymphangiogenic therapy. We assume
      that the antigen-presenting cells will have a different maturity level and that
      more tolerogenic effector cells (regulatory T cells, Tregs) develop in the
      absence of lymphatic vessels. Current anti(lymph)angiogenic therapies have the
      disadvantage that they are primarily effective on actively growing vessels. Most
      patients who receive high-risk keratoplasty often present in the clinic with
      already established, mature corneal blood and lymphatic vessels. At present,
      there are no lymph vessel regressing strategies, and the mechanisms regulating
      the maturation of the lymphatics are largely unknown. Therefore, our second goal
      is to develop new strategies for the regression of existing, pathological
      lymphatic vessels in the cornea. We are testing both destructive strategies, such
      as photodynamic therapy and diathermy as well as strategies for the molecular
      destabilization of the lymph vessel endothelium. Thus, our project identifies the
      precise mechanisms by which anti-lymphangiogenic therapies improve transplant
      survival, and we are developing new strategies to push back mature lymphatics in
      the high-risk setting.

PMID- 28505677
TI  - [Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental
      Dry Eye Disease].
AB  - Purpose Aging is an important factor in dry-eye disease that has not been studied
      in the context of therapeutic measures. Aging-associated modifications of the
      ocular immune system implicate that anti-inflammatory therapies may act
      differently among younger individuals in terms of onset and effect of different
      substances. The goal of this study was to determine differences in clinical
      phenotype and topical anti-inflammatory therapy using a desiccating stress mouse
      model. Methods An experimental dry-eye disease (desiccating stress model) was
      induced in 12-week and 12-month-old female BALB/c mice. Topical therapy included
      0.05% cyclosporine/F4H5 (Novaliq), F4H5, 0.05% cyclosporine (Restasis(r),
      Allergan) and dexamethasone (Monodex(r), Thea Pharma) for 3 consecutive weeks. A
      control group received no therapy whatsoever. Readout parameters included tear
      secretion, corneal fluorescein staining at 5 timepoints and histological analysis
      of goblet cell count at the end of the experiments. Results The older mice
      demonstrated a significantly stronger dry eye phenotype than the younger mice.
      Following therapy, the older mice responded to topical anti-inflammatory therapy
      significantly later than the younger individuals. Regarding the different
      substances used, cyclosporine/F4H5 showed a significantly faster decrease in
      corneal fluoresceine staining after only 1 week of therapy in comparison to all
      other groups. This substance was also superior regarding tear secretion and
      goblet cell count in age matched groups and in comparison to younger mice.
      Conclusions These experimental data support the implication that aging should be
      considered as an important factor in daily clinical practice. Furthermore, the
      differences found between substance classes, such as calcineurin antagonists and
      steroids, as well as different drug formulations, should be considered in future
      pre-clinical and clinical trials.

PMID- 28505676
TI  - [New Therapeutic Approaches in Inflammatory Diseases of the Eye - Targeting
      Lymphangiogenesis and Cellular Immunity: Research Unit FOR 2240 Presents Itself].
AB  - Background Ophthalmology, principally, is a very successful subdiscipline in
      medicine. Nonetheless, there are still unmet medical needs which necessitate
      translational research. Methods The funding instrument of a Research Unit (RU) of
      the German Research Foundation (DFG) is presented as exemplified by the RU 2240
      at the Department of Ophthalmology at the University of Cologne. Results The
      Research Unit integrates different research groups working on pathologic ocular
      inflammation, macrophages/microglia and (lymph)angiogenesis to collaborate in a
      synergistic way. Rotation positions allow young clinicians to rotate into
      research labs for a defined period of time. A Research Unit is also a powerful
      strategic tool to strengthen clinical and experimental ophthalmology at
      individual medical faculties. Conclusions The funding instrument of a Research
      Unit is highly suitable for fostering translational research in a medical
      subdiscipline such as ophthalmology, supporting the next generation of
      (clinician) scientists in ophthalmology and finding new cures for our patients.

PMID- 28505678
TI  - Is the Correlation between Salivary Cortisol and Serum Cortisol Reliable Enough
      to Enable Use of Salivary Cortisol Levels in Preterm Infants?

PMID- 28505679
TI  - Achievement of Body Mass Index Specific Weight Gain Recommendations: Impact on
      Preterm Birth in Twin Pregnancies.

PMID- 28505680
TI  - The Role of Interleukin-6 and Interleukin-8 Circulating Cytokines in
      Differentiating between Feeding Intolerance and Necrotizing Enterocolitis in
      Preterm Infants.

PMID- 28505681
TI  - Prenatal Care Adherence and Neonatal Intensive Care Unit Admission or Stillbirth
      among Women with Gestational and Preexisting Diabetes Mellitus.
AB  - OBJECTIVE:  To determine if there was an association between prenatal care
      adherence and neonatal intensive care unit (NICU) admission or stillbirth, and
      adverse perinatal outcomes in women with preexisting diabetes mellitus (DM) and
      gestational DM (GDM). MATERIALS AND METHODS:  This is a retrospective cohort
      study among women with DM and GDM at a Diabetes in Pregnancy Program at an
      academic institution between 2006 and 2014. Adherence with prenatal care was the
      percentage of prenatal appointments attended divided by those scheduled.
      Adherence was divided into quartiles, with the first quartile defined as lower
      adherence and compared with the other quartiles. RESULTS:  There were 443 women
      with DM and 499 with GDM. Neonates of women with DM and lower adherence had
      higher rates of NICU admission or stillbirth (55 vs. 39%; p = 0.003). A
      multivariable logistic regression showed that the lower adherence group had
      higher likelihood of NICU admission (adjusted odds ratio: 1.61 [1.03-2.5]; p =
      0.035). Those with lower adherence had worse glycemic monitoring and more
      hospitalizations. Among those with GDM, most outcomes were similar between groups
      including NICU admission or stillbirth. CONCLUSION:  Women with DM with lower
      adherence had higher rates of NICU admission and worse glycemic control. Most
      outcomes among women with GDM with lower adherence were similar.

PMID- 28505682
TI  - [Implementation of a Laparoscopic Simulation Training in Undergraduate Medical
      Education - The Lubeck Toolbox-Curriculum].
AB  - BACKGROUND: Simulation-based training has become increasingly relevant in
      minimally invasive surgery (MIS). It is unclear whether or not the established
      Lubeck Toolbox (LTB) Curriculum for the acquisition of basic MIS skills can be
      implemented to supplement standard undergraduate education in surgery and how it
      would be accepted. MATERIALS UND METHODS: Since 04/2015, students at the medical
      school of the University of Lubeck have had the option to complete the highly
      standardized and validated LTB Curriculum. It consists of six subsequent tasks
      with pre-defined learning goals. Video tutorials allow for a self-educating
      approach. The individual training progress is documented continuously as
      scheduled by the curriculum. The program was evaluated in a standardized manner
      using an established online platform for the evaluation of university courses at
      the University of Lubeck. RESULTS: Between 04/2015 and 07/2016, 63 students
      completed the LTB Curriculum. The general interest in a surgical specialty rose
      from an average of 1.61 (SD 0.78) before to 1.12 after the curriculum. The
      numbers of required repetitions for the training tasks 1 - 6 were median 24 (6 -
      79), 23 (5 - 61), 7 (5 - 33), 15 (5 - 59), 16 (5 - 50), and 18 (7 - 48),
      respectively. None of the 63 students terminated the curriculum prematurely. On
      average, 4.35 (SD 1.58) hours per week were spent training with an overall
      duration of 4.1 (SD 1.2) weeks required to go through the LTB Curriculum.
      Evaluation results showed an overall rating of 1.0 (SD 0.17). The average
      learning progress, didactics and structure of the curriculum were rated as 1.0
      (SD 0.24), 1.14 (SD 0.36), and 1.0 (SD 0.24), respectively. The relevance for the
      following study years and the future professional activity was reported to be 1.2
      (SD 0.45) on average. CONCLUSION: As an addition to the regular undergraduate
      program, the Lubeck Toolbox Curriculum was well accepted by many students.
      Evaluation showed exceedingly positive results. Furthermore, the data suggest
      that the LTB Curriculum may increase the interest in a surgical specialty among
      medical students. This aspect seems to be relevant in times where surgeons should
      make every effort to recruit young doctors for surgical residency.

PMID- 28505683
TI  - Tranexamic Acid Effectively Reduces Blood Loss and Transfusion Rates during
      Simultaneous Bilateral Total Knee Arthroplasty.
AB  - Tranexamic acid (TXA) can reduce blood loss and decrease transfusion rates after
      total knee arthroplasty (TKA). The purpose of our study was to evaluate the
      efficacy of TXA in a homogenous, consecutive cohort of patients undergoing
      simultaneous bilateral primary TKA. This was a retrospective study of 50
      consecutive patients who underwent bilateral simultaneous primary TKA between
      2011 and 2015. Of these, 20 patients received TXA and 30 patients did not receive
      TXA and served as the control group. Primary outcome measurements were
      intraoperative estimated blood loss, hemoglobin (Hb) and Hematocrit (Hct) levels
      on postoperative day (POD) 1 and POD2, and blood transfusion rates. Secondary
      outcomes included length of stay (LOS), knee flexion/extension range of motion
      (ROM), and postoperative complications. There was no difference between groups
      for preoperative Hb and Hct (all p > 0.05). The TXA group demonstrate higher Hb
      levels at POD1 (11.7 in TXA vs. 10.4 controls; p < 0.001) and POD2 (10.5 in TXA
      vs. 9.6 controls; p < 0.001), as well as higher Hct levels at POD1 (35.6 in TXA
      vs. 32.1 controls; p < 0.001) and POD2 (31.9 in TXA vs. 29.3 controls; p <
      0.001). There was less percentage variation in Hb levels in the TXA group from
      preoperative to POD1 (17.7% in TXA vs. 25.7% controls; p < 0.0001) and POD2
      (26.1% TXA vs. 31.8% controls; p = 0.019). Similarly, less percentage variation
      in Hct levels in the TXA group from presurgery to POD1 (17.0% TXA vs. 25.7%
      controls; p < 0.0001) and POD2 (25.0% TXA vs. 31.3% controls; p = 0.005). A total
      of 23.3% of patients in the control group required transfusions compared with no
      patients in the TXA (p = 0.044). There were no differences in LOS, knee ROM, or
      number of complications. No thromboembolic events occurred. TXA in bilateral
      simultaneous TKA effectively reduces blood loss, maintains postoperative Hb and
      Hct levels, and significantly decreases blood transfusion rates. The level of
      evidence is level III (therapeutic study).

PMID- 28505684
TI  - Does Gender Influence How Patients Rate Their Patient Experience after Total Knee
      Arthroplasty?

PMID- 28505686
TI  - ?

PMID- 28505685
TI  - [Weaning Unit of the University Medicine Greifswald - Institutional Structure and
      Weaning Results from Prolonged Ventilation over 10 Years].
AB  - The increasing importance of intensive care medicine including mechanical
      ventilation has been accompanied by the demand of weaning opportunities for
      patients undergoing prolonged mechanical ventilation. Consequently, specialised
      clinical institutions, focusing on the weaning from mechanical ventilation, have
      been established since the 1980 s.The present article illustrates the structural
      development and results of such a specialised institution at the University
      Medicine Greifswald, using data of 616 patients collected within the past ten
      years (2006 - 2015). Across the years, a shift in the underlying disease leading
      to mechanical ventilation can be found, with rising numbers of patients suffering
      from pneumonia/sepsis and declining numbers of patients who underwent cardiac
      surgery in advance. The days with mechanical ventilation outside (p = 0.004) and
      within the investigated institution (p = 0.02) are significantly declining. The
      percentage of successfully weaned patients increased from 62.7 % (2006 - 2010) to
      77.3 % (2011 - 2015), p < 0.001. Consecutively, the percentage of patients who
      remained mechanically ventilated decreased from 16.4 % to 9.6 % (p < 0.001) and
      the share of in-hospital deceased patients significantly declined from 20.9 % to
      13.0 % (p < 0.001). Furthermore, the one-year-survival after hospital discharge
      in successful weaned patients was 72 percent. The present data, collected at the
      University Medicine Greifswald are quite comparable to data of other German
      institutions that are specialised on weaning from mechanical ventilation.

PMID- 28505687
TI  - [Exacerbation of COPD].
AB  - Acute worsenings of chronic obstructive pulmonary disease (COPD) were for a long
      time regarded as transient deteriorations, although occasionally life
      threatening. No connection to disease progression was recognized. Data emerging
      during the last decade showed that patients had a considerably worse survival
      outcome after severe exacerbations. This insight was consolidated in 2012 by a
      large population-based cohort analysis. At present, severe exacerbations are
      regarded as key risk factors for COPD disease progression. The present article
      summarises the current knowledge on exacerbations of COPD, as delineated during
      an expert workshop in February 2017. It comprises pathogenic mechanisms,
      exacerbation triggers, the characteristics of frequent exacerbators, and the
      predictors of worse survival outcome. The role of comorbidities is considered
      more closely. The presentation of the pharmacotherapy of acute exacerbation is
      supplemented by an overview of ventilatory support. Finally, pharmacological and
      nonpharmacological preventive measures are summarised.

PMID- 28505688
TI  - [Test Your Knowledge].

PMID- 28505690
TI  - Incidence of Low-Grade Testicular Injury in Orchidectomy Specimens Post
      testicular Torsion.
AB  - INTRODUCTION:  Following detorsion and orchidopexy for testicular torsion,
      predominantly animal studies have reported a risk of autoimmune and reperfusion
      injury to the contralateral testis. As a result, when testicular viability is
      compromised, orchidectomy is readily performed. This practice increases the
      likelihood of testes with potentially reversible injury being excised. We aim to
      determine the incidence of such occurrences and review the available evidence for
      and against early orchidectomy when testicular viability is doubtful. MATERIALS
      AND METHODS:  Data for a 15-year period from two pediatric institutions on
      testicular torsion in children younger than 16 years were reviewed. Using a
      previously published grading system, the orchidectomy specimens in this cohort
      with early low-grade injury were analyzed. Low-grade injury suggests the
      possibility of restitutio ad integrum implying restoration of exocrine and
      endocrine function of the affected testes. RESULTS:  Between both institutions,
      222 scrotal explorations were performed for testicular torsion; 20 neonatal and
      202 outside the neonatal period (age range [median]: 1-28 days [3 days] and 3
      months-16 years [13 years], respectively). Of these scrotal explorations, 17
      neonatal and 66 nonneonatal orchidectomies were required (85 vs. 33%,
      respectively; p < 0.0001). From these orchidectomy specimens, 5 (6%) were found
      to have low-grade injury. The ages of these five children ranged from 9 to 16
      years (median 15, mean 13.6 years). Their symptom duration ranged from 8 to 37
      hours (median 14, mean 18 hours) and two of these children had a preoperative
      ultrasound documenting no flow to the testis. CONCLUSION:  The finding of
      histopathological features that may represent salvageability of a torted testis
      occurs relatively rarely. Because of this possibility, appropriate intraoperative
      steps to check for reperfusion must be undertaken prior to orchidectomy. More
      evidence for the use of antioxidants and tunica albuginea decompression to
      improve testes salvage rates is required. The potential for exocrine and
      endocrine function if partial testicular atrophy occurs and the evidence for
      contralateral autoimmune testicular damage in pre- and postpubertal males require
      further investigation.

PMID- 28505689
TI  - [Pain Management in Palliative Care].
AB  - A consistent pain management together with treatment of dyspnoea belongs to the
      main issues in symptom control in particular in palliative thoracic oncology.
      Together with the medicamentous therapy the psychologic and social circumstances
      of the affected patients have to be considered as factors influencing the
      experience of pain. The therapeutic fundament according to the WHO guideline for
      cancer pain is the opiate based medicamentous adjustment combined with non
      opioids. In principle, this should be performed preferably orally, as simply as
      possible, according to a fix drug schedule and individually adjusted to the
      needed dosage. Breakthrough pain has to be treated with rapidly efficacious, non
      retarded analgetics. The typical adverse reaction profile for opiates like
      constipation and initial nausea should be considered prophylactically by applying
      concurrent medication with adjuvants. Co-analgesic drugs like anticonvulsiva or
      corticosteroids could support the analgetic effect and are used preferably in
      case of neuropathic pain. Primary aim in analgesic therapy is to achieve the best
      possible pain reduction and hence to safeguard quality of life.

PMID- 28505691
TI  - Laparoscopic Pyloromyotomy: A Study of the Learning Curve.
AB  - INTRODUCTION:  Laparoscopic pyloromyotomy (LPM) is a minimally invasive surgical
      technique used in pyloric stenosis treatment. This technique is safe, effective,
      and does not show more complications than laparotomy. Nevertheless, this
      technique requires an acquisition period to be optimally applied. This study
      analyses the learning curve of LPM. MATERIALS AND METHODS:  Seven surgeons were
      retrospectively evaluated on their 40 first LPM. Patient data were recorded,
      including peroperative data (operation length and complications) and
      postoperative recoveries (renutrition, vomiting, and complications). The learning
      curves were evaluated and each variable was compared with the different moments
      of the learning curve. RESULTS:  The mean operative time is 25 +/- 11 minutes. It
      significantly decreases with the learning curve (p < 0.01). Ten procedures were
      necessary to acquire the operative technics. However, postoperative complications
      with a necessary redo procedure appear after the 10th patient. There is no
      significant difference concerning long-term postoperative complications according
      to the learning curve and to surgeons. The best results are recorded after the
      20th patients. Hospital length of stay also decreases significantly after the
      10th procedure. The recorded postoperative vomiting is independent to the
      operative time as the ad libitum feedings recovery. CONCLUSION:  The learning
      curve of LPM is cut into three stages. Only 10 cases are needed to acquire the
      gesture. Complications appear after this acquirement period.

PMID- 28505692
TI  - Outcome after Hypospadias Repair: Evaluation Using the Hypospadias Objective
      Penile Evaluation Score.
AB  - INTRODUCTION:  The Hypospadias Objective Penile Evaluation Score (HOPE-Score) is
      a concise and reproducible way to describe hypospadias severity. We classified
      boys undergoing primary hypospadias repair to determine the correlation between
      the HOPE-Score and the severity of hypospadias first and the outcome after
      surgery second. MATERIALS AND METHODS:  Patients who underwent primary
      hypospadias repair from 2005 to 2014 were identified. An independent physician
      assessed retrospectively the HOPE-Score, using photographies of the patients
      before, after primary surgery, and after all necessary surgeries. The correlation
      between the HOPE-Score and the severity of hypospadias, on the one hand, and the
      outcome after surgery, on the other hand, were analyzed. RESULTS:  The HOPE-Score
      was assessed preoperatively for 79 boys, postoperatively for 66, and after all
      necessary surgeries for 21 patients. Mean HOPE-Score reached 30.2 +/- 5.9 before
      surgery, 42.2 +/- 6.1 after primary surgery, and 43.7 +/- 3.4 after all necessary
      surgeries. A significant correlation between the HOPE-Score and the severity of
      hypospadias before surgery was observed. The boys with glanular hypospadias
      scored significantly higher (36.3 +/- 5.4) than those with distal (29.6 +/- 4.4)
      and proximal hypospadias (21.1 +/- 3.5). Furthermore, a significant correlation
      between the HOPE-Score and the outcome after hypospadias repair was observed.
      Patients who needed no reintervention after primary hypospadias repair scored
      significantly higher postoperatively (45.1 +/- 5.4) than those who needed a
      second (40.8 +/- 4.2) or more than two surgeries (36.9 +/- 7.4). CONCLUSION:  The
      HOPE-Score is a good system to assess the severity of hypospadias and the
      cosmetic outcome after hypospadias repair.

PMID- 28505693
TI  - Pediatric Surgery: Job or Vocation?

PMID- 28505694
TI  - Acute Idiopathic Scrotal Edema: Systematic Literature Review.
AB  - INTRODUCTION:  Existing information on acute idiopathic scrotal edema relies on
      small case series and textbooks. METHODS:  We searched reports with no date
      limits on acute idiopathic scrotal edema. RESULTS:  Thirty-seven studies were
      included. Sixteen case series addressed the prevalence of acute idiopathic
      scrotal edema among males with acute scrotum: among 3,403 cases, the diagnosis of
      acute idiopathic scrotal edema was made in 413 cases (12%). Twenty-four reports
      addressed history, findings, management, and course of acute idiopathic scrotal
      edema in 311 patients. The patients mostly ranged in age from 5 to 8 years,
      presented with acute scrotal redness and swelling, associated or not with mild
      pain. Ninety percent or more of the cases developed in patients without atopic
      diathesis and were not preceded by inguinoscrotal surgery, acute febrile
      illnesses, or trauma. They were afebrile; in good general condition; and
      presented without pruritus, nausea or vomiting, or abdominal pain. The lesions
      were bilateral in two-thirds and unilateral in one-third of the cases. The
      condition resolved spontaneously within 2 to 3 days without sequelae.
      Approximately 10% of the cases experienced a recurrence. CONCLUSION:  Acute
      idiopathic scrotal edema is a self-limiting condition that accounts for >= 10% of
      cases of acute scrotum in children and adolescents.

PMID- 28505695
TI  - The Status of Junior Pediatric Surgeons in Europe: Old Challenges, New
      Opportunities.

PMID- 28505696
TI  - [Can the "Rule of Rescue" be rescued? A comment on Weyma Lubbe's "Rule of Rescue
      vs. Rescue of statistical life"].
AB  - In her article "Rule of Rescue vs. Rescue of statistical lives" [1] Weyma Lubbe
      elevates gut feelings supporting the "rule of rescue" to "civic judgments".
      Without doubt in a constitutional democracy ultimately the judgments and
      aspirations of citizens must be decisive. Yet, particularly in the field of
      health policy, the bias to overemphasize what are closer rather than more remote,
      concrete rather than abstract consequences, should be counteracted not supported.
      The utility forgone by observing the "rule of rescue" in health care must be held
      against it. Making the "opportunity costs" of applying the rule of rescue visible
      is part of the citizens' "health ethic information package" and not as such an
      attack on the "Rule of Rescue".

PMID- 28505697
TI  - [The Development of Palliative Care Hospital Support Teams (HPCTs) in Bavaria
      from 2011-2015: Tasks, Acceptance, Structure and Funding].
AB  - INTRODUCTION: Palliative care hospital support teams (HPCTs) provide inpatients
      from all departments palliative medical support. Seriously ill as well as dying
      patients, who are being treated in facilities that do not have their own
      palliative care unit, can benefit from these multi-professional teams just as
      much as patients who do not (yet) need to be admitted to a palliative care unit.
      At the end of 2015, 53 HPCTs, which were in accordance with the requirements
      established in the "Program for HPCTs" by the Bavarian Ministry of Health in
      2009, had been approved in Bavaria. METHODS: Using a questionnaire that was
      distributed by mail (2011) and an online survey (2015), we asked all Bavarian
      HPCTs, which had been approved up until then, to answer questions regarding their
      tasks, the level of acceptance within their hospital, the structure of their
      staff and funding. In addition to questions, which were rated on an applicability
      scale from 0 to 10, there was also room for written comments. RESULTS: The return
      rate in 2011 was 77% (17 questionnaires) and 53% (28) in 2015. In sum, HPCTs were
      widely regarded as a suitable instrument for improving in-house palliative care
      (2011: median 7.8 (0-10) +/-1.9, 2015: 7.2 (0-10) +/-2.3; n.s.). The level of
      acceptance among the other departments of the hospital was assessed as being
      significantly higher in 2015 (7.2+/-2.3) than it was 4 years earlier (5.7+/-2.2;
      p<0.05). HPCTs cover various tasks, most commonly including "supportive
      conversations," "accompaniment in the dying phase," "pain therapy" and "discharge
      management." However, a decline in multi-professionalism within the teams could
      be seen, especially in the fields of psychology/psycho-oncology and spiritual
      care (p<0.05). Both surveys showed that an essential aspect in funding the teams
      was the supplementary payment ZE 60 for "complex palliative medical treatments."
      However, funding in general was predominantly reported as being quite difficult:
      only 29% of the HPCTs of 2015 indicated that all of their costs were covered.
      CONCLUSION: HPCTs in Bavaria take over important tasks in caring for seriously
      ill and dying patients and their families. According to their own appraisal, the
      level of acceptance within hospitals is improving. The hope is that new
      regulations, such as the new OPS 8-98 h (specialized complex palliative
      treatments provided by a HPCT), which was introduced in 2017, will solidify
      funding without jeopardizing the multi-professionalism that characterizes HPCTs.

PMID- 28505698
TI  - [Internet Use by Oncology Outpatients: Results of a Survey in Germany].
AB  - Objective Internet has become an important source of information for cancer
      patients regarding disease and treatment. A national survey was conducted to
      assess the importance of Internet in the routine care of cancer patients in
      Germany. Method The cross-sectional survey included 5,984 outpatients (56.7%
      female, M=64.3 years, SD=12). 3 groups were identified: Internet users, non-users
      whose families/friends did online research for them, and "complete" non-users.
      The data was analyzed using descriptive statistics and group comparisons. Results
      1 patient in 2 used the Internet to research health-related information. Internet
      users considered this research to be helpful, felt better able to participate in
      health-related decisions, and less alone with their disease. However, the
      information found online contributed to a feeling of uncertainty. 72.5% of
      Internet users researched treatment options and 21.3% talked to their doctor
      about their research. Conclusion The Internet was shown to be an important source
      of information for cancer patients. For patients to be able to use Internet
      research meaningfully, it could be helpful that they receive support from their
      oncologist.

PMID- 28505699
TI  - [Psychological Stress in Hospital Nursing Staff: Effects of Status and
      Organizational Structures].
AB  - OBJECTIVE: The study investigates the impact of organizational structures in
      hospitals on nursing staff's psychological stress. The stress level that is
      caused by the specific working conditions of a major hospital is presented in a
      cross-sectional analysis differentiated by organizational categories with regard
      to effects of structure and status. METHODS: Data were collected via Impuls-Test
      and by a context-specific supplementary questionnaire among the registered
      nursing staff of a major maximum care hospital. For analysis of the data, we used
      the effort-reward-imbalance and the job-demand-control model as well as an
      average calculation of 13 different dimensions of working conditions,
      differentiated by organizational categories. RESULTS AND CONCLUSION: The results
      show that the nursing staff's level of psychological stress can only be
      understood against the background of their organizational involvement and
      position in the hospital. The effects clearly vary in terms of organizational
      unit, working hour model and status and position occupied.

PMID- 28505700
TI  - [The Role of Municipalities in Lower Saxony for Future Physician's Care - A
      Survey of Mayors and District Administrators].
AB  - BACKGROUND: Comprehensive outpatient medical care is being increasingly
      threatened due to the decreasing willingness of physicians to establish their
      practices in rural areas. Partly, municipalities feel impelled to support doctors
      setting up their practices with their own resources. The aim of this study was to
      get the community perspective on the ambulatory care situation and to examine the
      role and influence of the local authorities. METHODS: The mayors (n=411) and
      district administrators (n=38) in Lower Saxony received a self-developed written
      questionnaire in September 2015 (comprehensive survey). RESULTS: The response
      rate was 72%. Availability of general practitioners was considered as inadequate
      by 30% of those surveyed and 71% described specialist care as being insufficient.
      Two-thirds of respondents saw local problems with filling vacant doctors'
      offices. 42% of mayors and 65% of district administrators said they had already
      supported outpatient doctors. The most frequent measures carried out so far
      included financial support, consulting services and the development of
      cooperation and networks. The majority considered the model of medical care
      centers being operated under municipal sponsorship to be unsuitable in principle.
      CONCLUSIONS: Local governments prevalently see problems with filling vacant
      doctors' offices as well as a need for local support. A significant proportion of
      municipalities has already implemented various support measures. Community
      participation in the outpatient care with medical care centers under municipal
      sponsorship is assessed rather critically.

PMID- 28505701
TI  - [Compatibility of Work and Family Life: Survey of Physicians in the Munich
      Metropolitan Area].
AB  - Aim Investigation of the compatibility of work and family life for physicians in
      the Munich metropolitan area. Methods Survey of a representative sample of 1,800
      physicians using a questionnaire. Results Men were less satisfied (7% very
      satisfied vs. 21%) with compatibility between work and family life than women.
      The group least satisfied overall was hospital-based physicians (p=0.000, chi
      square=122.75). Women rather than men cut back their career due to children,
      perceived their professional advancement as impaired, desisted from establishing
      private practice or quit hospital employment altogether. Respondents strove for
      flexible childcare and makeshift solution if the established service failed. Most
      did not have that at their disposal. Hospital-based physicians wished for
      predictable working hours, and would like to have a say in the structure of their
      schedule. For the majority this was not the case. While for 80% it would be
      important to participate in the definition of their working hours, this was only
      possible in 17%. 86% found the opportunity to work part-time important, but many
      doctors (more than 30%) did not have that option. The biggest help for office
      based physicians would be an expedited procedure by the Bavarian Association of
      Statutory Health Insurance Physicians (KVB) when applying for a proxy. The second
      most important would be the ability to hand over on-call duties. 36% of
      respondents felt that compatibility of work and family life was best achieved
      outside of patient care, during residency 42% believed this to be the case. Only
      6% of physicians felt the best compatibility to be achieved in a hospital. Among
      the physician owners of practices, 34% considered their model to be the best way
      to reconcile both aspects of life. Conclusion More flexible options for childcare
      and more influence on the definition of working hours are necessary in order to
      better reconcile work and family life. For office-based physicians it must be
      made easier to find a substitute. Currently, especially women consider children
      as hindering their careers. Hospitals are perceived as extremely unfavorable
      workplaces for achieving compatibility between work and family life.

PMID- 28505702
TI  - [Recalculation of Tobacco-Attributable Mortality: National and Regional Data for
      Germany].
AB  - Introduction Tobacco use accounts for about 5 million annual premature deaths
      worldwide. Tobacco thus is the single most important preventable health risk. In
      this paper we present a recalculation of tobacco-attributable mortality in
      Germany, and examine gender and regional differences. Data and Methods The
      calculation is based on the prevalence of current and former smokers, the
      relative mortality risks for diseases for which tobacco use is associated with an
      increased mortality risk, and the number of deaths by ICD-10 diagnoses. For the
      first time, colorectal and liver cancer as well as type 2 diabetes and
      tuberculosis were taken into consideration. Results In 2013, 121 087 deaths were
      attributable to smoking (i. e. 13.5% of all deaths), including 84 782 deaths in
      men and 36 305 deaths in women. The tobacco-attributable mortality rate was
      higher in men than in women, and in terms of regional discrepancies a north-south
      gradient was observed. Conclusion The number of tobacco-attributable deaths is
      substantial and higher than previously predicted. Compared to 2007, numbers have
      increased in absolute terms, whereas in relative terms the tobacco-attributable
      mortality rate declined. Given processes of demographic aging, a continued rise
      in absolute numbers of tobacco-attributable mortality is to be expected in the
      future.

PMID- 28505703
TI  - [Benefit and Sustainability of Networks for workplace Health Promotion in SME
      Examined at the SME Networks "Bewegte Unternehmen" and "Vitale Unternehmen"].
AB  - PURPOSE: The purpose of the study was to analyze if 2 regional networks of small
      and medium enterprises (SME) for workplace health promotion are sustainable, and
      to find out the motivation of the enterprises to join the network. It was also
      examined if there is a stable culture of cooperation 6 -10 years after the
      founding of the network. Additionally, the study checked the current work and
      suggestions for improvement to the network structure, so that in the future,
      promotion of workplace health can be further improved. METHOD: 2 regional
      networks, founded in 2005 and 2009, were studied. Standardized telephone
      interviews carried out between September 2013 and January 2014 enabled data
      collection for this cross-sectional study. 42 interviews with 6 open questions
      were organized with the managers of the companies or the person responsible for
      workplace health promotion. RESULTS: The results of the study show that 88.1%
      (n=37) of the network company members profited from the exchange of experiences.
      50.0% (n=21) benefited from shared activities and 28.6% (n=12) from making new
      contacts. 9.5% (n=4) of the respondents expressed concerns about excessive
      bureaucracy resulting in too much effort for too little benefit and 7.1% (n=3)
      were also missing comprehensive structural measures. Suggestions for improvement
      were enhancement of practical work (26.2%, n=11) and the wish for stronger
      commitment (11.9%, n=5). 90.5% (n=38) considered their expectations as fulfilled
      and 66.7% (n=28) evaluated the current work as being quite positive. CONCLUSION:
      The networks have turned out to be sustainable, proven by the fact that the
      companies still are members of the networks for 6 and 10 years, respectively and
      are still satisfied with the network. The study shows that the majority of the
      members profits from the membership of these regional networks. Networks can help
      them to implement permanent workplace health promotion. To further improve the
      work of the network, a systematic and scientific workplace health promotion
      scheme is recommended.

PMID- 28505704
TI  - [Compilation of Second Opinion Programs in the German Statutory Health
      Insurance].
AB  - OBJECTIVE: According to a new legislation passed in 2016, patients with an
      indication for elective procedures have the right to obtain a second opinion. The
      Federal Joint Committee has not yet provided a list of indications that this
      legislation will cover. Independently of this, the statutory health insurances
      can, nonetheless, pay for a second opinion. The aim of this article is to give an
      overview of current second opinion programs delivered by the statutory health
      insurance schemes. METHODS: Websites of all German statutory health insurance
      schemes (n=117) were searched for second opinion programs and their features in
      November 2016. All data was extracted by one person and verified by a second
      person. RESULTS: In total, 78 second-opinion programs were identified. Half of
      all statutory health insurance schemes (50%, n=59) provide at least one second
      opinion program. The majority of them was in the field of orthopedics (78%, n=61)
      and oncology (58%, n=45). Multiple replies were possible. In most cases, second
      opinion programs were outsourced (58%; n=44), followed by forwarding patients to
      health service providers contracted with the statutory health insurance scheme
      (45% n=34). Only in 11% (n=8) was the second opinion delivered by staff of the
      statutory health insurance scheme. The second opinion was delivered based on
      submitted documents only (63%; n=48), direct patient-physician contact (43%;
      n=33), and contact by phone (14%; n=11). The delivery of the second opinion took
      7 days in median, while the delivery based on submitted documents only (median 7)
      was faster than the delivery by direct-physician contact (median 14).
      CONCLUSIONS: The majority of those living in Germany have the possibility to
      obtain a second opinion. However, second-opinion programs are very heterogeneous
      so that patients are confused about their rights to second opinion.

PMID- 28505705
TI  - Crossed ectopic kidney: prenatal diagnosis and postnatal follow-up.
AB  - OBJECTIVE: The objective of this study is to investigate prenatal diagnosis and
      postnatal outcome of fetuses with crossed ectopic kidney. METHOD: Cases referred
      for an empty renal fossa and diagnosed with crossed ectopic kidney confirmed
      postnatally were analyzed retrospectively over a period of 10 years. Prenatal
      diagnosis was established following the detection of one kidney in a normal
      position and a second ipsilateral kidney fed by abnormal blood vessels on Doppler
      flow RESULTS: Between 2005 and 2015, 185 fetuses were referred for an empty renal
      fossa. Crossed ectopic kidney was diagnosed in 10 of them. Associated congenital
      urological anomalies included two cases of double collecting system and bilateral
      hydronephrosis in one. Associated extra renal findings were single umbilical
      artery (4/10), ventricular septal defects (1/10), and persistent left superior
      vena cava (1/10). On postnatal follow-up, bilateral vesicoureteral reflux was
      diagnosed in a case who presented prenatally with bilateral hydronephrosis and
      two cases of mild hydronephrosis. All cases were managed conservatively.
      CONCLUSION: Crossed ectopic kidney should be suspected in cases presenting with
      an empty renal fossa and a normal positioned kidney. Thorough anatomical scan
      should be performed as well as periodic follow-up throughout pregnancy. Postnatal
      nephrological follow-up is recommended. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28505706
TI  - The three-vessel and trachea view (3VTV) in the first trimester of pregnancy: an
      additional tool in screening for congenital heart defects (CHD) in an unselected
      population.
AB  - OBJECTIVE: The aim of the study was to evaluate the feasibility of obtaining the
      three-vessel and trachea view (3VTV) in an unselected population undergoing first
      trimester screening for aneuploidy, and to investigate its role in the early
      detection of congenital heart defects (CHD). METHODS: Cardiac examination was
      performed by expert sonographers. Abnormal findings of 3VTV were classified in
      three different subgroups: number, size and spatial relationship of the vessels.
      RESULTS: We enrolled 6350 consecutive singleton pregnancies and included 5343
      cases. Examination of 3VTV was feasible in 94% of cases. Fifty-seven (1%) CHD
      were present in the study period; 24 cases were excluded because parents opted
      for termination of pregnancy. Of the remaining 33 cases, 25 were suspected at the
      first trimester and eight were detected only at the mid-trimester. An abnormal
      3VTV was suspected in 22 cases, and it was confirmed in 21. Five cases that were
      erroneously classified in the subgroup of abnormal vessel number were actually
      characterized by a diminutive size of one of the great arteries. The detection
      rate for CHD, including 4-CV and 3VTV, was 75.8%. CONCLUSIONS: Our study
      demonstrates that 3VTV is an easy plane to obtain by expert sonographers in an
      unselected population during first trimester. Typical suspicions include
      detection of abnormal number, size or spatial relationship of the vessels. (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28505708
TI  - Decomposition of strongly charged topological defects.
AB  - We study decomposition of geometrically enforced nematic topological defects
      bearing relatively large defect strengths m in effectively two-dimensional planar
      systems. Theoretically, defect cores are analyzed within the mesoscopic Landau-de
      Gennes approach in terms of the tensor nematic order parameter. We demonstrate a
      robust tendency of defect decomposition into elementary units where two
      qualitatively different scenarios imposing total defect strengths on a nematic
      region are employed. Some theoretical predictions are verified experimentally,
      where arrays of defects bearing charges m=+/-1 and even m=+/-2 are enforced
      within a plane-parallel nematic cell using an atomic force microscopy scribing
      method.

PMID- 28505707
TI  - Numerical heating of electrons in particle-in-cell simulations of fully
      magnetized plasmas.
AB  - The role of spatial resolution of the electron gyroradius in electrostatic
      particle-in-cell (PIC) simulations is studied. It is demonstrated that resolving
      the gyroradius is crucial for simulations of strongly magnetized plasmas and that
      nonresolving it results in substantial anisotropic heating of electrons. The
      numerical heating can, in some cases, be suppressed by the higher-order weighting
      to the grid, but it cannot be avoided. Possible mechanisms behind this numerical
      heating are discussed. The study is carried out with a fully three dimensional
      electrostatic PIC code with an external magnetic and electric fields.

PMID- 28505709
TI  - Causal influence in linear Langevin networks without feedback.
AB  - The intuition of causation is so fundamental that almost every research study in
      life sciences refers to this concept. However, a widely accepted formal
      definition of causal influence between observables is still missing. In the
      framework of linear Langevin networks without feedback (linear response models)
      we propose a measure of causal influence based on a new decomposition of
      information flows over time. We discuss its main properties and we compare it
      with other information measures like the transfer entropy. We are currently
      unable to extend the definition of causal influence to systems with a general
      feedback structure and nonlinearities.

PMID- 28505710
TI  - Temperature of a single chaotic eigenstate.
AB  - The onset of thermalization in a closed system of randomly interacting bosons at
      the level of a single eigenstate is discussed. We focus on the emergence of Bose
      Einstein distribution of single-particle occupation numbers, and we give a local
      criterion for thermalization dependent on the eigenstate energy. We show how to
      define the temperature of an eigenstate, provided that it has a chaotic structure
      in the basis defined by the single-particle states. The analytical expression for
      the eigenstate temperature as a function of both interparticle interaction and
      energy is complemented by numerical data.

PMID- 28505711
TI  - Critical behavior of hard squares in strong confinement.
AB  - We examine the phase behavior of a quasi-one-dimensional system of hard squares
      with side-length sigma, where the particles are confined between two parallel
      walls and only nearest-neighbor interactions occur. As in our previous work
      [Gurin, Varga, and Odriozola, Phys. Rev. E 94, 050603 (2016)]2470
      004510.1103/PhysRevE.94.050603, the transfer operator method is used, but here we
      impose a restricted orientation and position approximation to yield an analytic
      description of the physical properties. This allows us to study the parallel
      fluid-like to zigzag solid-like structural transition, where the compressibility
      and heat capacity peaks sharpen and get higher as H->H_{c}=2sqrt[2]-1~1.8284 and
      p->p_{c}=infinity. Here H is the width of the channel measured in sigma units and
      p is the pressure. We have found that this structural change becomes critical at
      the (p_{c},H_{c}) point. The obtained critical exponents belong to the
      universality class of the one-dimensional Ising model. We believe this behavior
      holds for the unrestricted orientational and positional case.

PMID- 28505712
TI  - Sugar export limits size of conifer needles.
AB  - Plant leaf size varies by more than three orders of magnitude, from a few
      millimeters to over one meter. Conifer leaves, however, are relatively short and
      the majority of needles are no longer than 6 cm. The reason for the strong
      confinement of the trait-space is unknown. We show that sugars produced near the
      tip of long needles cannot be exported efficiently, because the pressure required
      to drive vascular flow would exceed the greatest available pressure (the osmotic
      pressure). This basic constraint leads to the formation of an inactive region of
      stagnant fluid near the needle tip, which does not contribute to sugar flow.
      Remarkably, we find that the size of the active part does not scale with needle
      length. We predict a single maximum needle size of 5 cm, in accord with data from
      519 conifer species. This could help rationalize the recent observation that
      conifers have significantly smaller leaves than angiosperms, and provide a
      biophysical explanation for this intriguing difference between the two largest
      groups of plants.

PMID- 28505713
TI  - Molecular dynamics studies of electron-ion temperature equilibration in hydrogen
      plasmas within the coupled-mode regime.
AB  - We use classical molecular dynamics (MD) to study electron-ion temperature
      equilibration in two-component plasmas in regimes for which the presence of
      coupled collective modes has been predicted to substantively reduce the
      equilibration rate. Guided by previous kinetic theory work, we examine hydrogen
      plasmas at a density of n=10^{26}cm^{-3}, T_{i}=10^{5}K, and
      10^{7}K<T_{e}<10^{9}K. The nonequilibrium classical MD simulations are performed
      with interparticle interactions modeled by quantum statistical potentials (QSPs).
      Our MD results indicate (i) a large effect from time-varying potential energy,
      which we quantify by appealing to an adiabatic two-temperature equation of state,
      and (ii) a notable deviation in the energy equilibration rate when compared to
      calculations from classical Lenard-Balescu theory including the QSPs. In
      particular, it is shown that the energy equilibration rates from MD are more
      similar to those of the theory when coupled modes are neglected. We suggest
      possible reasons for this surprising result and propose directions of further
      research along these lines.

PMID- 28505714
TI  - Interactions of localized wave structures and dynamics in the defocusing coupled
      nonlinear Schrodinger equations.
AB  - We investigate the defocusing coupled nonlinear Schrodinger equations from a 3*3
      Lax pair. The Darboux transformations with the nonzero plane-wave solutions are
      presented to derive the newly localized wave solutions including dark-dark and
      bright-dark solitons, breather-breather solutions, and different types of new
      vector rogue wave solutions, as well as interactions between distinct types of
      localized wave solutions. Moreover, we analyze these solutions by means of
      parameters modulation. Finally, the perturbed wave propagations of some obtained
      solutions are explored by means of systematic simulations, which demonstrates
      that nearly stable and strongly unstable solutions. Our research results could
      constitute a significant contribution to explore the distinct nonlinear waves
      (e.g., dark solitons, breather solutions, and rogue wave solutions) dynamics of
      the coupled system in related fields such as nonlinear optics, plasma physics,
      oceanography, and Bose-Einstein condensates.

PMID- 28505715
TI  - Statistical properties of the one-dimensional Burridge-Knopoff model of
      earthquakes obeying the rate- and state-dependent friction law.
AB  - Statistical properties of the one-dimensional spring-block (Burridge-Knopoff)
      model of earthquakes obeying the rate- and state-dependent friction law are
      studied by extensive computer simulations. The quantities computed include the
      magnitude distribution, the rupture-length distribution, the main shock
      recurrence-time distribution, the seismic-time correlations before and after the
      main shock, the mean slip amount, and the mean stress drop at the main shock,
      etc. Events of the model can be classified into two distinct categories. One
      tends to be unilateral with its epicenter located at the rim of the rupture zone
      of the preceding event, while the other tends to be bilateral with enhanced
      "characteristic" features resembling the so-called "asperity." For both types of
      events, the distribution of the rupture length L_{r} exhibits an exponential
      behavior at larger sizes, ~exp[-L_{r}/L_{0}] with a characteristic "seismic
      correlation length" L_{0}. The mean slip as well as the mean stress drop tends to
      be rupture-length independent for larger events. The continuum limit of the model
      is examined, where the model is found to exhibit pronounced characteristic
      features. In the continuum limit, the characteristic rupture length L_{0} is
      estimated to be ~100 [km]. This means that, even in a hypothetical homogenous
      infinite fault, events cannot be indefinitely large in the exponential sense, the
      upper limit being of order ~10^{3} kilometers. Implications to real seismicity
      are discussed.

PMID- 28505716
TI  - Central loops in random planar graphs.
AB  - Random planar graphs appear in a variety of contexts and it is important for many
      different applications to be able to characterize their structure. Local
      quantities fail to give interesting information and it seems that path-related
      measures are able to convey relevant information about the organization of these
      structures. In particular, nodes with a large betweenness centrality (BC) display
      nontrivial patterns, such as central loops. We first discuss empirical results
      for different random planar graphs and we then propose a toy model which allows
      us to discuss the condition for the emergence of nontrivial patterns such as
      central loops. This toy model is made of a star network with N_{b} branches of
      size n and links of weight 1, superimposed to a loop at distance l from the
      center and with links of weight w. We estimate for this model the BC at the
      center and on the loop and we show that the loop can be more central than the
      origin if w<w_{c} where the threshold of this transition scales as w_{c}~n/N_{b}.
      In this regime, there is an optimal position of the loop that scales as
      l_{opt}~N_{b}w/4. This simple model sheds some light on the organization of these
      random structures and allows us to discuss the effect of randomness on the
      centrality of loops. In particular, it suggests that the number and the spatial
      extension of radial branches are the crucial ingredients that control the
      existence of central loops.

PMID- 28505717
TI  - Localized growth and branching random walks with time correlations.
AB  - We generalize a model of growth over a disordered environment, to a large class
      of Ito processes. In particular, we study how the microscopic properties of the
      noise influence the macroscopic growth rate. The present model can account for
      growth processes in large dimensions and provides a bed to understand better the
      tradeoff between exploration and exploitation. An additional mapping to the
      Schrodinger equation readily provides a set of disorders for which this model can
      be solved exactly. This mean-field approach exhibits interesting features, such
      as a freezing transition and an optimal point of growth, which can be studied in
      detail, and gives yet another explanation for the occurrence of the Zipf law in
      complex, well-connected systems.

PMID- 28505718
TI  - Mechanics of a granular skin.
AB  - Magic sand, a hydrophobic toy granular material, is widely used in popular
      science instructions because of its nonintuitive mechanical properties. A
      detailed study of the failure of an underwater column of magic sand shows that
      these properties can be traced to a single phenomenon: the system self-generates
      a cohesive skin that encapsulates the material inside. The skin, consisting of
      pinned air-water-grain interfaces, shows multiscale mechanical properties: they
      range from contact-line dynamics in the intragrain roughness scale, to plastic
      flow at the grain scale, all the way to sample-scale mechanical responses. With
      decreasing rigidity of the skin, the failure mode transforms from brittle to
      ductile (both of which are collective in nature) to a complete disintegration at
      the single-grain scale.

PMID- 28505719
TI  - Active rotational and translational microrheology beyond the linear spring
      regime.
AB  - Active particle tracking microrheometers have the potential to perform accurate
      broadband measurements of viscoelasticity within microscopic systems. Generally,
      their largest possible precision is limited by Brownian motion and low frequency
      changes to the system. The signal to noise ratio is usually improved by
      increasing the size of the driven motion compared to the Brownian as well as
      averaging over repeated measurements. New theory is presented here whereby error
      in measurements of the complex shear modulus can be significantly reduced by
      analyzing the motion of a spherical particle driven by nonlinear forces. In some
      scenarios error can be further reduced by applying a variable transformation
      which linearizes the equation of motion. This enables normalization that
      eliminates error introduced by low frequency drift in the particle's equilibrium
      position. Our measurements indicate that this can further resolve an additional
      decade of viscoelasticity at high frequencies. Using this method will easily
      increase the signal strength enough to significantly reduce the measurement time
      for the same error. Thus the method is more conducive to measuring
      viscoelasticity in slowly changing microscopic systems, such as a living cell.

PMID- 28505720
TI  - First-principles equation-of-state table of silicon and its effects on high
      energy-density plasma simulations.
AB  - Using density-functional theory-based molecular-dynamics simulations, we have
      investigated the equation of state for silicon in a wide range of plasma density
      and temperature conditions of rho=0.001-500g/cm^{3} and T=2000-10^{8}K. With
      these calculations, we have established a first-principles equation-of-state
      (FPEOS) table of silicon for high-energy-density (HED) plasma simulations. When
      compared with the widely used SESAME-EOS model (Table 3810), we find that the
      FPEOS-predicted Hugoniot is ~20% softer; for off-Hugoniot plasma conditions, the
      pressure and internal energy in FPEOS are lower than those of SESAME EOS for
      temperatures above T ~ 1-10 eV (depending on density), while the former becomes
      higher in the low-T regime. The pressure difference between FPEOS and SESAME 3810
      can reach to ~50%, especially in the warm-dense-matter regime. Implementing the
      FPEOS table of silicon into our hydrocodes, we have studied its effects on Si
      target implosions. When compared with the one-dimensional radiation-hydrodynamics
      simulation using the SESAME 3810 EOS model, the FPEOS simulation showed that (1)
      the shock speed in silicon is ~10% slower; (2) the peak density of an in-flight
      Si shell during implosion is ~20% higher than the SESAME 3810 simulation; (3) the
      maximum density reached in the FPEOS simulation is ~40% higher at the peak
      compression; and (4) the final areal density and neutron yield are, respectively,
      ~30% and ~70% higher predicted by FPEOS versus the traditional simulation using
      SESAME 3810. All of these features can be attributed to the larger
      compressibility of silicon predicted by FPEOS. These results indicate that an
      accurate EOS table, like the FPEOS presented here, could be essential for the
      precise design of targets for HED experiments.

PMID- 28505721
TI  - Criticality and mechanical enhancement in composite fiber networks.
AB  - Many biological materials consist of sparse networks of disordered fibers,
      embedded in a soft elastic matrix. The interplay between rigid and soft elements
      in such composite networks leads to mechanical properties that can go far beyond
      the sum of those of the constituents. Here we present lattice-based simulations
      to unravel the microscopic origins of this mechanical synergy. We show that the
      competition between fiber stretching and bending and elastic deformations of the
      matrix gives rise to distinct mechanical regimes, with phase transitions between
      them that are characterized by critical behavior and diverging strain
      fluctuations and with different mechanisms leading to mechanical enhancement.

PMID- 28505723
TI  - Effects of film growth kinetics on grain coarsening and grain shape.
AB  - We study models of grain nucleation and coarsening during the deposition of a
      thin film using numerical simulations and scaling approaches. The incorporation
      of new particles in the film is determined by lattice growth models in three
      different universality classes, with no effect of the grain structure. The first
      model of grain coarsening is similar to that proposed by Saito and Omura [Phys.
      Rev. E 84, 021601 (2011)PLEEE81539-375510.1103/PhysRevE.84.021601], in which
      nucleation occurs only at the substrate, and the grain boundary evolution at the
      film surface is determined by a probabilistic competition of neighboring grains.
      The surface grain density has a power-law decay, with an exponent related to the
      dynamical exponent of the underlying growth kinetics, and the average radius of
      gyration scales with the film thickness with the same exponent. This model is
      extended by allowing nucleation of new grains during the deposition, with
      constant but small rates. The surface grain density crosses over from the initial
      power law decay to a saturation; at the crossover, the time, grain mass, and
      surface grain density are estimated as a function of the nucleation rate. The
      distributions of grain mass, height, and radius of gyration show remarkable power
      law decays, similar to other systems with coarsening and particle injection, with
      exponents also related to the dynamical exponent. The scaling of the radius of
      gyration with the height h relative to the base of the grain show clearly
      different exponents in growth dominated by surface tension and growth dominated
      by surface diffusion; thus it may be interesting for investigating the effects of
      kinetic roughening on grain morphology. In growth dominated by surface diffusion,
      the increase of grain size with temperature is observed.

PMID- 28505722
TI  - Direct observation of coupling between orientation and flow fluctuations in a
      nematic liquid crystal at equilibrium.
AB  - To demonstrate coupling between orientation and flow fluctuations in a nematic
      liquid crystal at equilibrium, we simultaneously observe the intensity change due
      to director fluctuations under a polarizing microscope and the Brownian motion of
      a fluorescent particle trapped weakly by optical tweezers. The calculated cross
      correlation function of the particle position and the spatial gradient of the
      intensity is nonzero, clearly indicating the existence of coupling.

PMID- 28505724
TI  - Critical nucleus size for crystallization of supercooled liquids in two
      dimensions.
AB  - Using molecular dynamics simulations, we study the crystallization of supercooled
      liquids in two dimensions in which particles interact with other particles via
      the Lennard-Jones-Gauss potential. We first prepare supercooled liquids at
      various temperatures by rapid quenching from the melt. The simulations are
      performed with a crystalline seed inserted at the center of the initial system.
      We investigate the time evolution of the inserted nucleus and its surroundings
      and determine the critical nucleus size n_{c} defined as the smallest nucleus
      which survives. The results show that n_{c} scales as ~(T_{m}-T)^{-2} with the
      melting temperature T_{m}, as expected in the classical nucleation theory. We
      also obtain the crystallization time at various temperatures as a function of
      nucleus size and show that the presence of a crystalline seed significantly
      affects the crystallization time when the temperature is higher than the
      characteristic temperature T^{*} at which the crystallization time becomes the
      shortest. This indicates that the crystallization is controlled by thermodynamics
      in this temperature range. When the temperature is lower than T^{*}, the effect
      of the inserted nucleus on crystallization is less significant, which indicates
      that crystallization is controlled by emergence and merging of small crystalline
      nuclei.

PMID- 28505725
TI  - Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions
      from normal arousal states to epileptic seizures.
AB  - A physiologically based corticothalamic model of large-scale brain activity is
      used to analyze critical dynamics of transitions from normal arousal states to
      epileptic seizures, which correspond to Hopf bifurcations. This relates an
      abstract normal form quantitatively to underlying physiology that includes neural
      dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that
      enables normal forms to be used to interpret quantitative data. The normal form
      of the Hopf bifurcations with delays is derived using Hale's theory, the center
      manifold theorem, and normal form analysis, and it is found to be explicitly
      expressed in terms of transfer functions and the sensitivity matrix of a reduced
      open-loop system. It can be applied to understand the effect of each
      physiological parameter on the critical dynamics and determine whether the Hopf
      bifurcation is supercritical or subcritical in instabilities that lead to absence
      and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical
      nonlinearities on the bifurcation type are investigated, with implications for
      the roles of underlying physiology. The theoretical predictions about the
      bifurcation type and the onset dynamics are confirmed by numerical simulations
      and provide physiologically based criteria for determining bifurcation types from
      first principles. The results are consistent with experimental data from previous
      studies, imply that new regimes of seizure transitions may exist in clinical
      settings, and provide a simplified basis for control-systems interventions. Using
      the normal form, and the full equations from which it is derived, more complex
      dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the
      critical points of the subcritical Hopf bifurcations.

PMID- 28505726
TI  - Entrainment range of the suprachiasmatic nucleus affected by the difference in
      the neuronal amplitudes between the light-sensitive and light-insensitive
      regions.
AB  - Mammals not only can be synchronized to the natural 24-h light-dark cycle, but
      also to a cycle with a non-24-h period. The range of the period of the external
      cycle, for which the animals can be entrained to, is called the entrainment
      range, which differs among species. The entrainment range as a characteristic of
      the animal is determined by the main circadian clock, i.e., the suprachiasmatic
      nucleus (SCN) in the brain. The SCN is composed of ~10000 heterogeneous neurons,
      which can be divided into two subgroups, i.e., the ventrolateral subgroup (VL)
      directly receiving the light information from the retina and relaying the
      information to the dorsomedial subgroup (DM). Among the SCN neurons, the
      amplitudes are different; however, it is unclear that the amplitude is related to
      the location of the neurons in experiments. In the present study, we examined the
      effect of the difference in the neuronal amplitude between the VL and the DM on
      the entrainment range of the SCN, based on a mathematical model, i.e., the
      Poincare model, which is used to describe the circadian clock. We find that the
      maximal entrainment range is obtained when the difference is equal to a critical
      point. If the difference of the amplitudes of the VL neurons to the amplitudes of
      the DM neurons is smaller than a critical point, with the increase of the
      difference, the entrainment range of the SCN increases, while if the difference
      is larger than the critical point, the entrainment range decreases with the
      increase of the difference. Our finding may give a potential explanation for the
      diversity of the entrainment range among species.

PMID- 28505727
TI  - Multiple binding sites for transcriptional repressors can produce regular
      bursting and enhance noise suppression.
AB  - Cells may control fluctuations in protein levels by means of negative
      autoregulation, where transcription factors bind DNA sites to repress their own
      production. Theoretical studies have assumed a single binding site for the
      repressor, while in most species it is found that multiple binding sites are
      arranged in clusters. We study a stochastic description of negative
      autoregulation with multiple binding sites for the repressor. We find that
      increasing the number of binding sites induces regular bursting of gene products.
      By tuning the threshold for repression, we show that multiple binding sites can
      also suppress fluctuations. Our results highlight possible roles for the presence
      of multiple binding sites of negative autoregulators.

PMID- 28505729
TI  - Optimization of synchronizability in multiplex networks by rewiring one layer.
AB  - The mathematical framework of multiplex networks has been increasingly realized
      as a more suitable framework for modeling real-world complex systems. In this
      work, we investigate the optimization of synchronizability in multiplex networks
      by evolving only one layer while keeping other layers fixed. Our main finding is
      to show the conditions under which the efficiency of convergence to the most
      optimal structure is almost as good as the case where both layers are rewired
      during an optimization process. In particular, interlayer coupling strength
      responsible for the integration between the layers turns out to be a crucial
      factor governing the efficiency of optimization even for the cases when the layer
      going through the evolution has nodes interacting much more weakly than those in
      the fixed layer. Additionally, we investigate the dependency of synchronizability
      on the rewiring probability which governs the network structure from a regular
      lattice to the random networks. The efficiency of the optimization process
      preceding evolution driven by the optimization process is maximum when the fixed
      layer has regular architecture, whereas the optimized network is more
      synchronizable for the fixed layer having the rewiring probability lying between
      the small-world transition and the random structure.

PMID- 28505728
TI  - J-shaped stress-strain diagram of collagen fibers: Frame tension of triangulated
      surfaces with fixed boundaries.
AB  - We present Monte Carlo data of the stress-strain diagrams obtained using two
      different triangulated surface models. The first is the canonical surface model
      of Helfrich and Polyakov (HP), and the second is a Finsler geometry (FG) model.
      The shape of the experimentally observed stress-strain diagram is called J
      shaped. Indeed, the diagram has a plateau for the small strain region and becomes
      linear in the relatively large strain region. Because of this highly nonlinear
      behavior, the J-shaped diagram is far beyond the scope of the ordinary theory of
      elasticity. Therefore, the mechanism behind the J-shaped diagram still remains to
      be clarified, although it is commonly believed that the collagen degrees of
      freedom play an essential role. We find that the FG modeling technique provides a
      coarse-grained picture for the interaction between the collagen and the bulk
      material. The role of the directional degrees of freedom of collagen molecules or
      fibers can be understood in the context of FG modeling. We also discuss the
      reason for why the J-shaped diagram cannot (can) be explained by the HP (FG)
      model.

PMID- 28505730
TI  - Modeling mass transfer and reaction of dilute solutes in a ternary phase system
      by the lattice Boltzmann method.
AB  - In this work, we propose a general approach for modeling mass transfer and
      reaction of dilute solute(s) in incompressible three-phase flows by introducing a
      collision operator in lattice Boltzmann (LB) method. An LB equation was used to
      simulate the solute dynamics among three different fluids, in which the newly
      expanded collision operator was used to depict the interface behavior of dilute
      solute(s). The multiscale analysis showed that the presented model can recover
      the macroscopic transport equations derived from the Maxwell-Stefan equation for
      dilute solutes in three-phase systems. Compared with the analytical equation of
      state of solute and dynamic behavior, these results are proven to constitute a
      generalized framework to simulate solute distributions in three-phase flows,
      including compound soluble in one phase, compound adsorbed on single-interface,
      compound in two phases, and solute soluble in three phases. Moreover, numerical
      simulations of benchmark cases, such as phase decomposition, multilayered planar
      interfaces, and liquid lens, were performed to test the stability and efficiency
      of the model. Finally, the multiphase mass transfer and reaction in Janus droplet
      transport in a straight microchannel were well reproduced.

PMID- 28505732
TI  - Thermohydrodynamics of an evaporating droplet studied using a multiphase lattice
      Boltzmann method.
AB  - In this paper, the thermohydrodynamics of an evaporating droplet is investigated
      by using a single-component pseudopotential lattice Boltzmann model. The phase
      change is applied to the model by adding source terms to the thermal lattice
      Boltzmann equation in such a way that the macroscopic energy equation of
      multiphase flows is recovered. In order to gain an exhaustive understanding of
      the complex hydrodynamics during evaporation, a single droplet is selected as a
      case study. At first, some tests for a stationary (non-)evaporating droplet are
      carried out to validate the method. Then the model is used to study the
      thermohydrodynamics of a falling evaporating droplet. The results show that the
      model is capable of reproducing the flow dynamics and transport phenomena of a
      stationary evaporating droplet quite well. Of course, a moving droplet evaporates
      faster than a stationary one due to the convective transport. Our study shows
      that our single-component model for simulating a moving evaporating droplet is
      limited to low Reynolds numbers.

PMID- 28505731
TI  - Dewetting-mediated pattern formation inside the coffee ring.
AB  - The rearrangement of particles in the final stage of droplet evaporation has been
      investigated by utilizing differential interference contrast microscopy and the
      formation mechanism of a network pattern inside a coffee ring has been revealed.
      A tailored substrate with a circular hydrophilic domain is prepared to obtain
      thin liquid film containing monolayer particles. Real-time bottom-view images
      show that the evolution of a dry patch could be divided into three stages:
      rupture initiation, dry patch expansion, and drying of the residual liquid. A
      growing number of dry patches will repeat these stages to form the network
      patterns inside the ringlike stain. It can be shown that the suction effect
      promotes the rupture of the liquid film and the formation of the dry patch. The
      particle-assembling process is totally controlled by the liquid film dewetting
      and dominated by the surface tension of the liquid film, which eventually
      determine the ultimate deposition patterns.

PMID- 28505733
TI  - Reconstructing the structure of directed and weighted networks of nonlinear
      oscillators.
AB  - The formalism of complex networks is extensively employed to describe the
      dynamics of interacting agents in several applications. The features of the
      connections among the nodes in a network are not always provided beforehand,
      hence the problem of appropriately inferring them often arises. Here, we present
      a method to reconstruct directed and weighted topologies of networks of
      heterogeneous nonlinear oscillators. We illustrate the theory on a set of
      representative examples.

PMID- 28505734
TI  - Scaling dependence and synchronization of forced mercury beating heart systems.
AB  - We perform experiments on a nonautonomous Mercury beating heart system, which is
      forced to pulsate using an external square wave potential. At suitable
      frequencies and volumes, the drop exhibits pulsation with polygonal shapes having
      n corners. We find the scaling dependence of the forcing frequency nu_{n} on the
      volume V of the drop and establish the relationship nu_{n}?n/sqrt[V]. It is shown
      that the geometrical shape of substrate is important for obtaining closer match
      to these scaling relationships. Furthermore, we study synchronization of two
      nonidentical drops driven by the same frequency and establish that synchrony
      happens when the relationship n_{2}/n_{1}=sqrt[V_{2}/V_{1}] is satisfied.

PMID- 28505735
TI  - Statistical physics of the symmetric group.
AB  - Ordered chains (such as chains of amino acids) are ubiquitous in biological
      cells, and these chains perform specific functions contingent on the sequence of
      their components. Using the existence and general properties of such sequences as
      a theoretical motivation, we study the statistical physics of systems whose state
      space is defined by the possible permutations of an ordered list, i.e., the
      symmetric group, and whose energy is a function of how certain permutations
      deviate from some chosen correct ordering. Such a nonfactorizable state space is
      quite different from the state spaces typically considered in statistical physics
      systems and consequently has novel behavior in systems with interacting and even
      noninteracting Hamiltonians. Various parameter choices of a mean-field model
      reveal the system to contain five different physical regimes defined by two
      transition temperatures, a triple point, and a quadruple point. Finally, we
      conclude by discussing how the general analysis can be extended to state spaces
      with more complex combinatorial properties and to other standard questions of
      statistical mechanics models.

PMID- 28505736
TI  - Slip length of confined liquid with small roughness of solid-liquid interfaces.
AB  - We have studied the slip length of confined liquid with small roughness of solid
      liquid interfaces. Dyadic Green function and perturbation expansion have been
      applied to get the slip length quantitatively. In the slip length, both the
      effects of the roughness of the interfaces and the chemical interaction between
      the liquid and the solid surface are involved. For the numerical calculation,
      Monte Carlo method has been used to simulate the rough interfaces and the
      physical quantities are obtained statistically over the interfaces. Results show
      that the total slip length of the system is linearly proportional to the slip
      length contributed from the chemical interaction. And the roughness of the
      interfaces plays its role as the proportionality factor. For the roughness, the
      variance of the roughness decreases the total slip length while the correlation
      length of the roughness can enhance the slip length dramatically to a saturation
      value.

PMID- 28505737
TI  - Mechanism for Hall conductance of two-band systems against decoherence.
AB  - The Kubo formula expresses a linear response of the quantum system to weak
      classical fields. Previous studies showed that the environment degrades the
      quantum Hall conductance. By studying the dynamics of dissipative two-band
      systems, in this paper we find that the formation of system-environment bound
      states is responsible for the Hall conductance immune to the effect of the
      environment. The bound states can form only when the system-environment couplings
      are below a threshold. Our results may be of both theoretical and experimental
      interest in exploring dissipative topological insulators in realistic situations,
      and may open new perspectives for designing active quantum Hall devices working
      in realistic environments.

PMID- 28505738
TI  - Solution of the Lindblad equation for spin helix states.
AB  - Using Lindblad dynamics we study quantum spin systems with dissipative boundary
      dynamics that generate a stationary nonequilibrium state with a nonvanishing spin
      current that is locally conserved except at the boundaries. We demonstrate that
      with suitably chosen boundary target states one can solve the many-body Lindblad
      equation exactly in any dimension. As solution we obtain pure states at any
      finite value of the dissipation strength and any system size. They are
      characterized by a helical stationary magnetization profile and a ballistic spin
      current which is independent of system size, even when the quantum spin system is
      not integrable. These results are derived in explicit form for the one
      dimensional spin-1/2 Heisenberg chain and its higher-spin generalizations, which
      include the integrable spin-1 Zamolodchikov-Fateev model and the biquadratic
      Heisenberg chain.

PMID- 28505739
TI  - Avalanches dynamics in reaction fronts in disordered flows.
AB  - We report on numerical studies of avalanches of an autocatalytic reaction front
      in a porous medium. The front propagation is controlled by an adverse flow
      resulting in upstream, static, or downstream regimes. In an earlier study
      focusing on front shape, we identified three different universality classes
      associated with this system by following the front dynamics experimentally and
      numerically. Here, using numerical simulations in the vicinity of the second
      order transition, we identify an avalanche dynamics characterized by power-law
      distributions of avalanche sizes, durations, and lateral extensions. The related
      exponents agree well with the quenched-Kardar-Parisi-Zhang theory, which
      describes the front dynamics. However, the geometry of the propagating front
      differs slightly from that of the theoretical one. We show that this discrepancy
      can be understood in terms of the nonquasistatic correction induced by the finite
      front velocity.

PMID- 28505740
TI  - Weakly coupled map lattice models for multicellular patterning and collective
      normalization of abnormal single-cell states.
AB  - We present a weakly coupled map lattice model for patterning that explores the
      effects exerted by weakening the local dynamic rules on model biological and
      artificial networks composed of two-state building blocks (cells). To this end,
      we use two cellular automata models based on (i) a smooth majority rule (model I)
      and (ii) a set of rules similar to those of Conway's Game of Life (model II). The
      normal and abnormal cell states evolve according to local rules that are
      modulated by a parameter kappa. This parameter quantifies the effective weakening
      of the prescribed rules due to the limited coupling of each cell to its
      neighborhood and can be experimentally controlled by appropriate external agents.
      The emergent spatiotemporal maps of single-cell states should be of significance
      for positional information processes as well as for intercellular communication
      in tumorigenesis, where the collective normalization of abnormal single-cell
      states by a predominantly normal neighborhood may be crucial.

PMID- 28505741
TI  - Nonbacktracking expansion of finite graphs.
AB  - Message passing equations yield a sharp percolation transition in finite graphs,
      as an artifact of the locally treelike approximation. For an arbitrary finite,
      connected, undirected graph we construct an infinite tree having the same local
      structural properties as this finite graph, when observed by a nonbacktracking
      walker. Formally excluding the boundary, this infinite tree is a generalization
      of the Bethe lattice. We indicate an infinite, locally treelike, random network
      whose local structure is exactly given by this infinite tree. Message passing
      equations for various cooperative models on this construction are the same as for
      the original finite graph, but here they provide the exact solutions of the
      corresponding cooperative problems. These solutions are good approximations to
      observables for the models on the original graph when it is sufficiently large
      and not strongly correlated. We show how to express these solutions in the
      critical region in terms of the principal eigenvector components of the
      nonbacktracking matrix. As representative examples we formulate the problems of
      the random and optimal destruction of a connected graph in terms of our
      construction, the nonbacktracking expansion. We analyze the limitations and the
      accuracy of the message passing algorithms for different classes of networks and
      compare the complexity of the message passing calculations to that of direct
      numerical simulations. Notably, in a range of important cases, simulations turn
      out to be more efficient computationally than the message passing.

PMID- 28505742
TI  - Random versus maximum entropy models of neural population activity.
AB  - The principle of maximum entropy provides a useful method for inferring
      statistical mechanics models from observations in correlated systems, and is
      widely used in a variety of fields where accurate data are available. While the
      assumptions underlying maximum entropy are intuitive and appealing, its adequacy
      for describing complex empirical data has been little studied in comparison to
      alternative approaches. Here, data from the collective spiking activity of
      retinal neurons is reanalyzed. The accuracy of the maximum entropy distribution
      constrained by mean firing rates and pairwise correlations is compared to a
      random ensemble of distributions constrained by the same observables. For most of
      the tested networks, maximum entropy approximates the true distribution better
      than the typical or mean distribution from that ensemble. This advantage improves
      with population size, with groups as small as eight being almost always better
      described by maximum entropy. Failure of maximum entropy to outperform random
      models is found to be associated with strong correlations in the population.

PMID- 28505743
TI  - Complementary mode analyses between sub- and superdiffusion.
AB  - Several subdiffusive stochastic processes in nature, e.g., the motion of a tagged
      monomer in polymers, the height fluctuation of interfaces, particle dynamics in
      single-file diffusion, etc., can be described rigorously or approximately by the
      superposition of various modes whose relaxation times are broadly distributed. In
      this paper, we propose a mode analysis generating superdiffusion, which is paired
      with or complementary to subdiffusion. The key point in our discussion lies in
      the identification of a pair of conjugated variables, which undergo sub- and
      superdiffusion, respectively. We provide a simple interpretation for the sub- and
      superdiffusion duality for these variables using the language of polymer physics.
      The analysis also suggests the usefulness of looking at the force fluctuation in
      experiments, where a polymer is driven by a constant velocity.

PMID- 28505744
TI  - Equilibrium of fluid membranes endowed with orientational order.
AB  - Minimization of the low-temperature elastic free-energy functional of
      orientationlly ordered membranes involves independent variation of the membrane
      shape, while keeping the orientational order on it (its texture) fixed. We
      propose an operational, coordinate-independent method for implementing such a
      variation. Using the Nelson-Peliti formulation of elasticity that emphasizes the
      interplay between geometry, topology, and thermal fluctuations of orientationally
      ordered membranes, we minimize the elastic free energy to obtain equations
      governing their equilibrium shape, together with associated free boundary
      conditions. Our results are essential for understanding and predicting
      equilibrium shapes as well as textures of membranes and vesicles; particularly
      under conditions in which shape deformations are large.

PMID- 28505745
TI  - Ecological communities with Lotka-Volterra dynamics.
AB  - Ecological communities in heterogeneous environments assemble through the
      combined effect of species interaction and migration. Understanding the effect of
      these processes on the community properties is central to ecology. Here we study
      these processes for a single community subject to migration from a pool of
      species, with population dynamics described by the generalized Lotka-Volterra
      equations. We derive exact results for the phase diagram describing the dynamical
      behaviors, and for the diversity and species abundance distributions. A phase
      transition is found from a phase where a unique globally attractive fixed point
      exists to a phase where multiple dynamical attractors exist, leading to history
      dependent community properties. The model is shown to possess a symmetry that
      also establishes a connection with other well-known models.

PMID- 28505746
TI  - Alternative extrapolation-based symmetry boundary implementations for the
      axisymmetric lattice Boltzmann method.
AB  - In this study, alternative symmetry boundary implementations for the axisymmetric
      lattice Boltzmann (LB) method are proposed based on the nonequilibrium
      extrapolation and the direct extrapolation schemes. The proposed boundary schemes
      are directly implemented on the symmetry axis, and the postcollision distribution
      function and the macroscopic variables at the boundary nodes are extrapolated
      from the inner fluid nodes; thereby, the singularities arising at the symmetry
      axis (r=0) during the collision and the macroscopic variable calculations are
      completely avoided. The accuracy of the present schemes is consistent with the
      well-established axisymmetric LB model. Moreover, in comparison with previous
      symmetry boundary schemes, the present implementations are slightly more accurate
      than the symmetry scheme by Guo et al. [Phys. Rev. E 79, 046708
      (2009)10.1103/PhysRevE.79.046708] and numerically more stable than the specular
      reflection-based schemes.

PMID- 28505747
TI  - Influence of collective nonideal shielding on fusion reaction in partially
      ionized classical nonideal plasmas.
AB  - The collective nonideal effects on the nuclear fusion reaction process are
      investigated in partially ionized classical nonideal hydrogen plasmas. The
      effective pseudopotential model taking into account the collective and plasma
      shielding effects is applied to describe the interaction potential in nonideal
      plasmas. The analytic expressions of the Sommerfeld parameter, the fusion
      penetration factor, and the cross section for the nuclear fusion reaction in
      nonideal plasmas are obtained as functions of the nonideality parameter, Debye
      length, and relative kinetic energy. It is found that the Sommerfeld parameter is
      suppressed due to the influence of collective nonideal shielding. However, the
      collective nonideal shielding is found to enhance the fusion penetration factor
      in partially ionized classical nonideal plasmas. It is also found that the fusion
      penetration factors in nonideal plasmas represented by the pseudopotential model
      are always greater than those in ideal plasmas represented by the Debye-Huckel
      model. In addition, it is shown that the collective nonideal shielding effect on
      the fusion penetration factor decreases with an increase of the kinetic energy.

PMID- 28505748
TI  - Highly pressurized partially miscible liquid-liquid flow in a micro-T-junction.
      I. Experimental observations.
AB  - This is the first part of a two-part study on a partially miscible liquid-liquid
      flow (liquid carbon dioxide and deionized water) which is highly pressurized and
      confined in a microfluidic T-junction. Our main focuses are to understand the
      flow regimes as a result of varying flow conditions and investigate the
      characteristics of drop flow distinct from coflow, with a capillary number,
      Ca_{c}, that is calculated based on the continuous liquid, ranging from 10^{-3}
      to 10^{-2} (10^{-4} for coflow). Here in part I, we present our experimental
      observation of drop formation cycle by tracking drop length, spacing, frequency,
      and after-generation speed using high-speed video and image analysis. The drop
      flow is chronologically composed of a stagnating and filling stage, an elongating
      and squeezing stage, and a truncating stage. The common "necking" time during the
      elongating and squeezing stage (with Ca_{c}~10^{-3}) for the truncation of the
      dispersed liquid stream is extended, and the truncation point is subsequently
      shifted downstream from the T-junction corner. This temporal postponement effect
      modifies the scaling function reported in the literature for droplet formation
      with two immiscible fluids. Our experimental measurements also demonstrate the
      drop speed immediately following their generations can be approximated by the
      mean velocity from averaging the total flow rate over the channel cross section.
      Further justifications of the quantitative analysis by considering the mass
      transfer at the interface of the two partially miscible fluids are provided in
      part II.

PMID- 28505749
TI  - Highly pressurized partially miscible liquid-liquid flow in a micro-T-junction.
      II. Theoretical justifications and modeling.
AB  - This is the second part of a two-part study on a partially miscible liquid-liquid
      flow (carbon dioxide and deionized water) that is highly pressurized and confined
      in a microfluidic T-junction. In the first part of this study, we reported
      experimental observations of the development of flow regimes under various flow
      conditions and the quantitative characteristics of the drop flow including the
      drop length, after-generation drop speed, and periodic spacing development
      between an emerging drop and the newly produced one. Here in part II we provide
      theoretical justifications to our quantitative studies on the drop flow by
      considering (1) CO_{2} hydration at the interface with water, (2) the diffusion
      controlled dissolution of CO_{2} molecules in water, and (3) the diffusion
      distance of the dissolved CO_{2} molecules. Our analyses show that (1) the CO_{2}
      hydration at the interface is overall negligible, (2) a saturation scenario of
      the dissolved CO_{2} molecules in the vicinity of the interface will not be
      reached within the contact time between the two fluids, and (3) molecular
      diffusion does play a role in transferring the dissolved molecules, but the
      diffusion distance is very limited compared with the channel geometry. In
      addition, mathematical models for the drop length and the drop spacing are
      developed based on the observations in part I, and their predictions are compared
      to our experimental results.

PMID- 28505750
TI  - Convergence radius of perturbative Lindblad-driven nonequilibrium steady states.
AB  - We address the problem of analyzing the radius of convergence of perturbative
      expansion of nonequilibrium steady states of Lindblad-driven spin chains. A
      simple formal approach is developed for systematically computing the perturbative
      expansion of small driven systems. We consider the paradigmatic model of an open
      XXZ spin-1/2 chain with boundary-supported ultralocal Lindblad dissipators and
      treat two different perturbative cases: (i) expansion in the system-bath coupling
      parameter and (ii) expansion in the driving (bias) parameter. In the first case
      (i) we find that the radius of convergence quickly shrinks with increasing the
      system size, while in the second case (ii) we find that the convergence radius is
      always larger than 1, and in particular it approaches 1 from above as we change
      the anisotropy from an easy-plane (XY) to an easy-axis (Ising) regime.

PMID- 28505751
TI  - Anomalous scaling of stochastic processes and the Moses effect.
AB  - The state of a stochastic process evolving over a time t is typically assumed to
      lie on a normal distribution whose width scales like t^{1/2}. However, processes
      in which the probability distribution is not normal and the scaling exponent
      differs from 1/2 are known. The search for possible origins of such "anomalous"
      scaling and approaches to quantify them are the motivations for the work reported
      here. In processes with stationary increments, where the stochastic process is
      time-independent, autocorrelations between increments and infinite variance of
      increments can cause anomalous scaling. These sources have been referred to as
      the Joseph effect and the Noah effect, respectively. If the increments are
      nonstationary, then scaling of increments with t can also lead to anomalous
      scaling, a mechanism we refer to as the Moses effect. Scaling exponents
      quantifying the three effects are defined and related to the Hurst exponent that
      characterizes the overall scaling of the stochastic process. Methods of time
      series analysis that enable accurate independent measurement of each exponent are
      presented. Simple stochastic processes are used to illustrate each effect.
      Intraday financial time series data are analyzed, revealing that their anomalous
      scaling is due only to the Moses effect. In the context of financial market data,
      we reiterate that the Joseph exponent, not the Hurst exponent, is the appropriate
      measure to test the efficient market hypothesis.

PMID- 28505752
TI  - Surface switching statistics of rotating fluid: Disk-rim gap effects.
AB  - We examined the influence of internal noise on the irregular switching of the
      shape of the free surface of fluids in an open cylindrical vessel driven by a
      bottom disk rotating at constant speed [Suzuki, Iima, and Hayase, Phys. Fluids
      18, 101701 (2006)PHFLE61070-663110.1063/1.2359740]. A slight increase in the disk
      rim gap (less than 3% of the disk radius) was established experimentally to cause
      significant changes in this system, specifically, frequent appearance of the
      surface descending event connecting a nonaxisymmetric shape in strong mixing flow
      (turbulent flow) and an axisymmetric shape in laminar flow, as well as a shift in
      critical Reynolds number that define the characteristic states. The physical
      mechanism underlying the change is analyzed in terms of flow characteristics in
      the disk-rim gap, which acts as a noise source, and a mathematical model
      established from measurements of the surface height fluctuations with noise term.

PMID- 28505754
TI  - Generalized balance equations for charged particle transport via localized and
      delocalized states: Mobility, generalized Einstein relations, and fractional
      transport.
AB  - A generalized phase-space kinetic Boltzmann equation for highly nonequilibrium
      charged particle transport via localized and delocalized states is used to
      develop continuity, momentum, and energy balance equations, accounting explicitly
      for scattering, trapping and detrapping, and recombination loss processes.
      Analytic expressions detail the effect of these microscopic processes on mobility
      and diffusivity. Generalized Einstein relations (GER) are developed that enable
      the anisotropic nature of diffusion to be determined in terms of the measured
      field dependence of the mobility. Interesting phenomena such as negative
      differential conductivity and recombination heating and cooling are shown to
      arise from recombination loss processes and the localized and delocalized nature
      of transport. Fractional transport emerges naturally within this framework
      through the appropriate choice of divergent mean waiting time distributions for
      localized states, and fractional generalizations of the GER and mobility are
      presented. Signature impacts on time-of-flight current transients of
      recombination loss processes via both localized and delocalized states are
      presented.

PMID- 28505753
TI  - Forcing scheme analysis for the axisymmetric lattice Boltzmann method under
      incompressible limit.
AB  - Because the standard lattice Boltzmann (LB) method is proposed for Cartesian
      Navier-Stokes (NS) equations, additional source terms are necessary in the
      axisymmetric LB method for representing the axisymmetric effects. Therefore, the
      accuracy and applicability of the axisymmetric LB models depend on the forcing
      schemes adopted for discretization of the source terms. In this study, three
      forcing schemes, namely, the trapezium rule based scheme, the direct forcing
      scheme, and the semi-implicit centered scheme, are analyzed theoretically by
      investigating their derived macroscopic equations in the diffusive scale.
      Particularly, the finite difference interpretation of the standard LB method is
      extended to the LB equations with source terms, and then the accuracy of
      different forcing schemes is evaluated for the axisymmetric LB method.
      Theoretical analysis indicates that the discrete lattice effects arising from the
      direct forcing scheme are part of the truncation error terms and thus would not
      affect the overall accuracy of the standard LB method with general force term
      (i.e., only the source terms in the momentum equation are considered), but lead
      to incorrect macroscopic equations for the axisymmetric LB models. On the other
      hand, the trapezium rule based scheme and the semi-implicit centered scheme both
      have the advantage of avoiding the discrete lattice effects and recovering the
      correct macroscopic equations. Numerical tests applied for validating the
      theoretical analysis show that both the numerical stability and the accuracy of
      the axisymmetric LB simulations are affected by the direct forcing scheme, which
      indicate that forcing schemes free of the discrete lattice effects are necessary
      for the axisymmetric LB method.

PMID- 28505756
TI  - Interaction of Airy-Gaussian beams in photonic lattices with defects.
AB  - We investigate numerically the interaction between two finite Airy-Gaussian (AiG)
      beams in different media with the defected photonic lattices in one transverse
      dimension. We discuss that the beams with different intensities and phases launch
      into the different lattice structures but accelerate in opposite directions.
      During interactions, the interference fringe, breathers, and soliton pairs are
      observed. In the linear media, the initial deflection direction of the
      accelerated beams is changed by adjusting the phase shift and the beam interval.
      For a certain lattice period, the periodic interference fringe can form. A
      constructive or destructive interference can vary with the defect depth and phase
      shift. While the nonlinearity is introduced, the breathers is generated.
      Especially in the self-defocusing media, the appropriate AiG beam amplitude and
      lattice depth may lead to the formation of soliton pairs, On the contrary, the
      interaction of two Gaussian beams is diffraction.

PMID- 28505755
TI  - Dynamic scaling of island size distribution in submonolayer one-dimensional
      growth.
AB  - The dynamic scaling of the island size distribution (ISD) in the submonolayer
      growth regime of low-dimensional nanostructured systems is a long standing
      problem in epitaxial growth. In this study, kinetic Monte Carlo simulations of a
      realistic atomistic lattice-gas model describing the one-dimensional nucleation
      and growth of Al on Si(100):2*1 were performed to investigate the scaling
      behavior under varied growth conditions. Consistent with previous predictions,
      our results show that the shape of the scaled island size distribution can be
      altered by controlling the temperature and the C-defect density. The shifts in
      the scaled ISD are opposite to each other with temperature depending on the
      density of C-defects. For low C-defect density, a shift from a monomodal to a
      monotonically decreasing distribution as temperature increases is observed. We
      attribute the monomodal distribution to enhanced nucleation and aggregation
      whereas a monotonically decreasing distribution is attributed to restricted
      aggregation with defects playing only a minor role. At higher C-defect density,
      we show that the scaled ISD shift is from a monotonically decreasing to a
      monomodal distribution with increasing temperature. We argue that the reversal of
      the shift is due to competing effects introduced by high C-defect concentration.
      In addition, results show that the ISD is generally insensitive to flux
      variations and that at a high coverage regime the shift in the scaling behavior
      vanishes. Lastly, we posit that the shift in the scaled ISD indicates the
      departure of the island density's temperature dependence from predictions of
      classical nucleation theory.

PMID- 28505757
TI  - Explosive spreading on complex networks: The role of synergy.
AB  - In spite of the vast literature on spreading dynamics on complex networks, the
      role of local synergy, i.e., the interaction of elements that when combined
      produce a total effect greater than the sum of the individual elements, has been
      studied but only for irreversible spreading dynamics. Reversible spreading
      dynamics are ubiquitous but their interplay with synergy has remained unknown. To
      fill this knowledge gap, we articulate a model to incorporate local synergistic
      effect into the classical susceptible-infected-susceptible process, in which the
      probability for a susceptible node to become infected through an infected
      neighbor is enhanced when the neighborhood of the latter contains a number of
      infected nodes. We derive master equations incorporating the synergistic effect,
      with predictions that agree well with the numerical results. A striking finding
      is that when a parameter characterizing the strength of the synergy reinforcement
      effect is above a critical value, the steady-state density of the infected nodes
      versus the basic transmission rate exhibits an explosively increasing behavior
      and a hysteresis loop emerges. In fact, increasing the synergy strength can
      promote the spreading and reduce the invasion and persistence thresholds of the
      hysteresis loop. A physical understanding of the synergy promoting explosive
      spreading and the associated hysteresis behavior can be obtained through a mean
      field analysis.

PMID- 28505758
TI  - Machine learning applied to proton radiography of high-energy-density plasmas.
AB  - Proton radiography is a technique extensively used to resolve magnetic field
      structures in high-energy-density plasmas, revealing a whole variety of
      interesting phenomena such as magnetic reconnection and collisionless shocks
      found in astrophysical systems. Existing methods of analyzing proton radiographs
      give mostly qualitative results or specific quantitative parameters, such as
      magnetic field strength, and recent work showed that the line-integrated
      transverse magnetic field can be reconstructed in specific regimes where many
      simplifying assumptions were needed. Using artificial neural networks, we
      demonstrate for the first time 3D reconstruction of magnetic fields in the
      nonlinear regime, an improvement over existing methods, which reconstruct only in
      2D and in the linear regime. A proof of concept is presented here, with mean
      reconstruction errors of less than 5% even after introducing noise. We
      demonstrate that over the long term, this approach is more computationally
      efficient compared to other techniques. We also highlight the need for proton
      tomography because (i) certain field structures cannot be reconstructed from a
      single radiograph and (ii) errors can be further reduced when reconstruction is
      performed on radiographs generated by proton beams fired in different directions.

PMID- 28505759
TI  - Description of order-disorder transitions based on the phase-field-crystal model.
AB  - Order-disorder transition is an attractive topic in the research field of phase
      transformation. However, how to describe order-disorder transitions on atomic
      length scales and diffusional time scales is still challenging. Inspired from
      high-resolution transmission electron microscopy, we proposed an approach to
      describe ordered structures by introducing an order parameter into the original
      phase-field-crystal model to reflect the atomic potential distribution. This new
      order parameter contains information about kinds of atoms, showing that different
      kinds of sublattices in ordered structures can be distinguished by the amplitude
      of the order parameter. Two case studies, growth of ordered precipitations and
      evolution of antiphase domains, are also presented to demonstrate the
      capabilities of this approach.

PMID- 28505760
TI  - Proportional-integral control of propagating wave segments in excitable media.
AB  - Numerical simulations are performed to demonstrate that proportional-integral
      control, one of the most commonly used feedback schemes in control engineering,
      can stabilize propagating wave segments in excitable media to a desired size. The
      proportional-integral controller measures the size of a wave segment and applies
      a spatially uniform signal to the medium. This controller has the following
      features: difficult trial-and-error adjustment is not necessary, wave segments
      can be stabilized to different sizes without readjusting the controller, and the
      wave segment size can be maintained even in media having position-dependent
      parameters.

PMID- 28505761
TI  - Dispersive transport and symmetry of the dispersion tensor in porous media.
AB  - The macroscopic laws controlling the advection and diffusion of solute at the
      scale of the porous continuum are derived in a general manner that does not place
      limitations on the geometry and time evolution of the pore space. Special focus
      is given to the definition and symmetry of the dispersion tensor that is
      controlling how a solute plume spreads out. We show that the dispersion tensor is
      not symmetric and that the asymmetry derives from the advective derivative in the
      pore-scale advection-diffusion equation. When flow is spatially variable across a
      voxel, such as in the presence of a permeability gradient, the amount of
      asymmetry can be large. As first shown by Auriault [J.-L. Auriault et al. Transp.
      Porous Med. 85, 771 (2010)TPMEEI0169-391310.1007/s11242-010-9591-y] in the limit
      of low Peclet number, we show that at any Peclet number, the dispersion tensor
      D_{ij} satisfies the flow-reversal symmetry D_{ij}(+q)=D_{ji}(-q) where q is the
      mean flow in the voxel under analysis; however, Reynold's number must be
      sufficiently small that the flow is reversible when the force driving the flow
      changes sign. We also demonstrate these symmetries using lattice-Boltzmann
      simulations and discuss some subtle aspects of how to measure the dispersion
      tensor numerically. In particular, the numerical experiments demonstrate that the
      off-diagonal components of the dispersion tensor are antisymmetric which is
      consistent with the analytical dependence on the average flow gradients that we
      propose for these off-diagonal components.

PMID- 28505762
TI  - Asymptotic scaling properties and estimation of the generalized Hurst exponents
      in financial data.
AB  - We propose a method to measure the Hurst exponents of financial time series. The
      scaling of the absolute moments against the aggregation horizon of real financial
      processes and of both uniscaling and multiscaling synthetic processes converges
      asymptotically towards linearity in log-log scale. In light of this we found
      appropriate a modification of the usual scaling equation via the introduction of
      a filter function. We devised a measurement procedure which takes into account
      the presence of the filter function without the need of directly estimating it.
      We verified that the method is unbiased within the errors by applying it to
      synthetic time series with known scaling properties. Finally we show an
      application to empirical financial time series where we fit the measured scaling
      exponents via a second or a fourth degree polynomial, which, because of
      theoretical constraints, have respectively only one and two degrees of freedom.
      We found that on our data set there is not clear preference between the second or
      fourth degree polynomial. Moreover the study of the filter functions of each time
      series shows common patterns of convergence depending on the momentum degree.

PMID- 28505763
TI  - Comparative study of noise in low-current Townsend discharge in nitrogen and
      argon.
AB  - Noise in a low-current Townsend discharge in argon and nitrogen is studied.
      Experiments were performed in a "semiconductor-gas-discharge" structure
      constituted by a short plane-parallel discharge gap and a high-resistivity
      photosensitive semiconductor electrode. The noise of optical emission from gas
      excited by the discharge was investigated with a photomultiplier. Experiments
      were done at the room temperature of the discharge structure. According to the
      obtained data, the noise of discharge glow in Ar is astonishingly low-similar to
      that earlier found for the cryogenic discharge in this gas. At equal time-average
      photon fluxes emitted by discharges in both gases, the noise of gas glow in
      nitrogen substantially exceeds the corresponding value for argon. A statistical
      processing of signals of glow brightness for the two gases revealed the origin of
      this difference: While the power spectral density of noise in nitrogen is
      specified by a band of frequencies with the increased density, in argon it is
      nearly constant in an extended frequency range. At the same time, intensity of
      noise is practically the same for both gases in the ranges of low and high
      frequencies. The relationship of the increased noise in nitrogen with a low
      critical current density for oscillatory instability of the Townsend discharge in
      this gas is considered.

PMID- 28505764
TI  - Role of generosity and forgiveness: Return to a cooperative society.
AB  - One's reputation in human society depends on what and how one did in the past. If
      the reputation of a counterpart is too bad, we often avoid interacting with the
      individual. We introduce a selective cooperator called the goodie, who
      participates in the prisoner's dilemma game dependent on the opponent's
      reputation, and study its role in forming a cooperative society. We observe
      enhanced cooperation when goodies have a small but nonzero probability of playing
      the game with an individual who defected in previous rounds. Our finding implies
      that even this small generosity of goodies can provide defectors chances of
      encountering the better world of cooperation, encouraging them to escape from
      their isolated world of selfishness.

PMID- 28505765
TI  - Moment fluid equations for ions in weakly ionized plasma.
AB  - A one-dimensional fluid model for ions in weakly ionized plasma is proposed. The
      model differs from the existing ones in two aspects. First, a more accurate
      approximation of the collision terms in the fluid equations is suggested. For
      this purpose, the results obtained using the Monte Carlo kinetic model of the ion
      swarm experiments are considered. Second, the ion energy equation is taken into
      account. The fluid equations are closed using a simple model of the ion velocity
      distribution function. The accuracy of the fluid model is examined by comparing
      with the results of particle-in-cell Monte Carlo simulations. In particular,
      several test problems are considered using a parallel plate model of the
      capacitively coupled radio-frequency discharge. It is shown that the results
      obtained using the proposed fluid model are in good agreement with those obtained
      from the simulations over a wide range of discharge conditions. An approximation
      of the ion velocity distribution function for the problem under consideration is
      also discussed.

PMID- 28505766
TI  - Nucleation and growth of a core-shell composite nucleus by diffusion.
AB  - The critical radius of a core-shell-type nucleus grown by diffusion in a phase
      separated solution is studied. A kinetic critical radius rather than the
      thermodynamic critical radius of standard classical nucleation theory can be
      defined from the diffusional growth equations. It is shown that there exist two
      kinetic critical radii for the core-shell-type nucleus, for which both the inner
      core radius and the outer-shell radius will be stationary. Therefore, these two
      critical radii correspond to a single critical point of the nucleation path with
      a single energy barrier even though the nucleation looks like a two-step process.
      The two radii are given by formulas similar to that of classical nucleation
      theory if the Ostwald-Freundlich boundary condition is imposed at the surface of
      the inner nucleus and that of the outer shell. The subsequent growth of a core
      shell-type postcritical nucleus follows the classical picture of Ostwald's step
      rule. Our result is consistent with some of the experimental and numerical
      results which suggest the core-shell-type critical nucleus.

PMID- 28505767
TI  - Long-time predictability in disordered spin systems following a deep quench.
AB  - We study the problem of predictability, or "nature vs nurture," in several
      disordered Ising spin systems evolving at zero temperature from a random initial
      state: How much does the final state depend on the information contained in the
      initial state, and how much depends on the detailed history of the system? Our
      numerical studies of the "dynamical order parameter" in Edwards-Anderson Ising
      spin glasses and random ferromagnets indicate that the influence of the initial
      state decays as dimension increases. Similarly, this same order parameter for the
      Sherrington-Kirkpatrick infinite-range spin glass indicates that this information
      decays as the number of spins increases. Based on these results, we conjecture
      that the influence of the initial state on the final state decays to zero in
      finite-dimensional random-bond spin systems as dimension goes to infinity,
      regardless of the presence of frustration. We also study the rate at which spins
      "freeze out" to a final state as a function of dimensionality and number of
      spins; here the results indicate that the number of "active" spins at long times
      increases with dimension (for short-range systems) or number of spins (for
      infinite-range systems). We provide theoretical arguments to support these
      conjectures, and also study analytically several mean-field models: the random
      energy model, the uniform Curie-Weiss ferromagnet, and the disordered Curie-Weiss
      ferromagnet. We find that for these models, the information contained in the
      initial state does not decay in the thermodynamic limit-in fact, it fully
      determines the final state. Unlike in short-range models, the presence of
      frustration in mean-field models dramatically alters the dynamical behavior with
      respect to the issue of predictability.

PMID- 28505769
TI  - Controllability of giant connected components in a directed network.
AB  - When controlling a complex networked system it is not feasible to control the
      full network because many networks, including biological, technological, and
      social systems, are massive in size and complexity. But neither is it necessary
      to control the full network. In complex networks, the giant connected components
      provide the essential information about the entire system. How to control these
      giant connected components of a network remains an open question. We derive the
      mathematical expression of the degree distributions for four types of giant
      connected components and develop an analytic tool for studying the
      controllability of these giant connected components. We find that for both Erdos
      Renyi (ER) networks and scale-free (SF) networks with p fraction of remaining
      nodes, the minimum driver node density to control the giant component first
      increases and then decreases as p increases from zero to one, showing a peak at a
      critical point p=p_{m}. We find that, for ER networks, the peak value of the
      driver node density remains the same regardless of its average degree <k> and
      that it is determined by p_{m}<k>. In addition, we find that for SF networks the
      minimum driver node densities needed to control the giant components of networks
      decrease as the degree distribution exponents increase. Comparing the
      controllability of the giant components of ER networks and SF networks, we find
      that when the fraction of remaining nodes p is low, the giant in-connected, out
      connected, and strong-connected components in ER networks have lower
      controllability than those in SF networks.

PMID- 28505768
TI  - Community detection, link prediction, and layer interdependence in multilayer
      networks.
AB  - Complex systems are often characterized by distinct types of interactions between
      the same entities. These can be described as a multilayer network where each
      layer represents one type of interaction. These layers may be interdependent in
      complicated ways, revealing different kinds of structure in the network. In this
      work we present a generative model, and an efficient expectation-maximization
      algorithm, which allows us to perform inference tasks such as community detection
      and link prediction in this setting. Our model assumes overlapping communities
      that are common between the layers, while allowing these communities to affect
      each layer in a different way, including arbitrary mixtures of assortative,
      disassortative, or directed structure. It also gives us a mathematically
      principled way to define the interdependence between layers, by measuring how
      much information about one layer helps us predict links in another layer. In
      particular, this allows us to bundle layers together to compress redundant
      information and identify small groups of layers which suffice to predict the
      remaining layers accurately. We illustrate these findings by analyzing synthetic
      data and two real multilayer networks, one representing social support
      relationships among villagers in South India and the other representing shared
      genetic substring material between genes of the malaria parasite.

PMID- 28505770
TI  - Resonance phonon approach to phonon relaxation time and mean free path in one
      dimensional nonlinear lattices.
AB  - We extend a previously proposed resonance phonon approach that is based on the
      linear response theory. By studying the complex response function in depth, we
      work out the phonon relaxation time besides the oscillating frequency of the
      phonons in a few one-dimensional nonlinear lattices. The results in the large
      wave-number-k regime agree with the expectations of the effective phonon theory.
      However, in the small-k limit they follow different scaling laws. The phonon mean
      free path can also be calculated indirectly. It coincides well with that derived
      from the anharmonic phonon approach. A power-law divergent heat conduction, i.e.,
      the heat conductivity kappa depends on lattice length N by kappa~N^{beta} with
      beta>0, then is supported for the momentum-conserving lattices. Furthermore, this
      approach can be applied to diatomic lattices. So obtained relaxation time
      quantitatively agrees with that from the effective phonon theory. As for the mean
      free path, the resonance phonon approach can detect both the acoustic and the
      optical branches, whereas the anharmonic phonon approach can only detect a
      combined branch, i.e., the acoustic branch for small k and the optical branch for
      large k.

PMID- 28505771
TI  - Counterexamples to Moffatt's statements on vortex knots.
AB  - One of the well-known problems of hydrodynamics is studied: the problem of
      classification of vortex knots for ideal fluid flows. In the literature there are
      known Moffatt statements that all torus knots K_{m,n} for all rational numbers
      m/n (0<m/n<infinity) are realized as vortex knots for each one of the considered
      axisymmetric fluid flows. We prove that actually such a uniformity does not exist
      because it does not correspond to the facts. Namely, we derive a complete
      classification of all vortex knots realized for the fluid flows studied by
      Moffatt and demonstrate that the real structure of vortex knots is much more rich
      because the sets of mutually nonisotopic vortex knots realized for different
      axisymmetric fluid flows are all different. An exact formula for the limit of the
      hydrodynamic safety factor q_{h} at a vortex axis is derived for arbitrary
      axisymmetric fluid equilibria. Another exact formula is obtained for the limit of
      the magnetohydrodynamics safety factor q at a magnetic axis for the general
      axisymmetric plasma equilibria.

PMID- 28505772
TI  - Fame and obsolescence: Disentangling growth and aging dynamics of patent
      citations.
AB  - We present an analysis of citations accrued over time by patents granted by the
      United States Patent and Trademark Office in 1998. In contrast to previous
      studies, a disaggregation by technology category is performed, and exogenously
      caused citation-number growth is controlled for. Our approach reveals an
      intrinsic citation rate that clearly separates into an-in the long run,
      exponentially time-dependent-aging function and a completely time-independent
      preferential-attachment-type growth kernel. For the general case of such a
      separable citation rate, we obtain the time-dependent citation distribution
      analytically in a form that is valid for any functional form of its aging and
      growth parts. Good agreement between theory and long-time characteristics of
      patent-citation data establishes our work as a useful framework for addressing
      still open questions about knowledge-propagation dynamics, such as the observed
      excess of citations at short times.

PMID- 28505773
TI  - Relativistic laser hosing instability suppression and electron acceleration in a
      preformed plasma channel.
AB  - The hosing processes of a relativistic laser pulse, electron acceleration, and
      betatron radiation in a parabolic plasma channel are investigated in the direct
      laser acceleration regime. It is shown that the laser hosing instability would
      result in the generation of a randomly directed off-axis electron beam and
      radiation source with a large divergence angle. While employing a preformed
      parabolic plasma channel, the restoring force provided by the plasma channel
      would correct the perturbed laser wave front and thus suppress the hosing
      instability. As a result, the accelerated electron beam and the emitted photons
      are well guided and concentrated along the channel axis. The employment of a
      proper plasma density channel can stably guide the relativistically intense laser
      pulse and greatly improve the properties of the electron beam and radiation
      source. This scheme is of great interest for the generation of high quality
      electron beams and radiation sources.

PMID- 28505774
TI  - Crater formation during raindrop impact on sand.
AB  - After a raindrop impacts on a granular bed, a crater is formed as both drop and
      target deform. After an initial, transient, phase in which the maximum crater
      depth is reached, the crater broadens outwards until a final steady shape is
      attained. By varying the impact velocity of the drop and the packing density of
      the bed, we find that avalanches of grains are important in the second phase and
      hence affect the final crater shape. In a previous paper, we introduced an
      estimate of the impact energy going solely into sand deformation and here we show
      that both the transient and final crater diameter collapse with this quantity for
      various packing densities. The aspect ratio of the transient crater is however
      altered by changes in the packing fraction.

PMID- 28505775
TI  - Criteria for infinite avalanches in the zero-temperature nonequilibrium random
      field Ising model on a Bethe lattice.
AB  - We present general criteria for the occurrence of infinite avalanches and
      critical hysteresis in the zero-temperature nonequilibrium random-field Ising
      model on a Bethe lattice. Drawing upon extant results as well as a result on a
      dilute four-coordinated (z=4) lattice, we show that diverging avalanches can
      occur if an arbitrarily small fraction of sites on a spanning cluster have
      connectivity z>=4.

PMID- 28505776
TI  - Thermal conductance of a two-level atom coupled to two quantum harmonic
      oscillators.
AB  - We have determined the thermal conductance of a system consisting of a two-level
      atom coupled to two quantum harmonic oscillators in contact with heat reservoirs
      at distinct temperatures. The calculation of the heat flux as well as the atomic
      population and the rate of entropy production are obtained by the use of a
      quantum Fokker-Planck-Kramers equation and by a Lindblad master equation. The
      calculations are performed for small values of the coupling constant. The results
      coming from both approaches show that the conductance is proportional to the
      coupling constant squared and that, at high temperatures, it is proportional to
      the inverse of temperature.

PMID- 28505777
TI  - Impact of the dipole contribution on the terahertz emission of air-based plasma
      induced by tightly focused femtosecond laser pulses.
AB  - The present paper studies the generation mechanism of terahertz (THz) radiation
      from tightly focused femtosecond laser pulses in a gas medium. We measured the
      angular radiation pattern under different focusing conditions and observed that,
      with the deepening of focus, the angular radiation pattern changes and optical-to
      THz conversion efficiency increases. The analysis of the observed phenomena led
      to the assumption that the dipole radiation prevails in most cases despite the
      existing conception regarding the dominating role of the quadrupole mechanism of
      radiation. Based on these assumptions, the transient photocurrent theory of the
      phenomenon presented in this paper was developed by us and used for the numerical
      fit of the experimental data.

PMID- 28505778
TI  - Outcomes of the collapse of a large bubble in water at high ambient pressures.
AB  - Presented here are observations of the outcomes of the collapses of large single
      bubbles in H_{2}O and D_{2}O at high ambient pressures. Experiments were carried
      out in a high-pressure spherical resonator at ambient pressures of up to 30 MPa
      and acoustic pressures up to 35 MPa. Monitoring of the collapse events and their
      outcomes was accomplished using multiframe high-speed photography. Among the
      observations to be presented are the temporal and spatial evolution of light
      emissions produced by the collapse events, which were observed to last on the
      order of 30 ns and have time independent radii on the order of 30MUm; the
      production of Rayleigh-Taylor jets which were observed to travel distances of up
      to 70MUm at speeds in excess of 4500 m/s; the entrainment of the light emitting
      regions in the jets' remnants; the production of spheroidal objects around the
      collapse points of the bubbles, far from any surface of the resonator; and the
      traversal and emergence of the Rayleigh-Taylor jets through the spherical
      objects. These spheroidal objects appear to behave as amorphous solids and form
      at locations where hydrodynamics predicts pressures in excess of the known
      transition pressures of water into the high-pressure crystalline ices, Ice-VI and
      Ice-VII.

PMID- 28505779
TI  - Quantum entanglement and temperature fluctuations.
AB  - In this paper, we consider entanglement in a system out of equilibrium, adopting
      the viewpoint given by the formalism of superstatistics. Such an approach yields
      a good effective description for a system in a slowly fluctuating environment
      within a weak interaction between the system and the environment. For this
      purpose, we introduce an alternative version of the formalism within a quantum
      mechanical picture and use it to study entanglement in the Heisenberg XY model,
      subject to temperature fluctuations. We consider both isotropic and anisotropic
      cases and explore the effect of different temperature fluctuations (chi^{2}, log
      normal, and F distributions). Our results suggest that particular fluctuations
      may enhance entanglement and prevent it from vanishing at higher temperatures
      than those predicted for the same system at thermal equilibrium.

PMID- 28505780
TI  - How the site degree influences quantum probability on inhomogeneous substrates.
AB  - We investigate the effect of the node degree and energy E on the electronic wave
      function for regular and irregular structures, namely, regular lattices,
      disordered percolation clusters, and complex networks. We evaluate the dependency
      of the quantum probability for each site on its degree. For a class of biregular
      structures formed by two disjoint subsets of sites sharing the same degree, the
      probability P_{k}(E) of finding the electron on any site with k neighbors is
      independent of E?0, a consequence of an exact analytical result that we prove for
      any bipartite lattice. For more general nonbipartite structures, P_{k}(E) may
      depend on E as illustrated by an exact evaluation of a one-dimensional
      semiregular lattice: P_{k}(E) is large for small values of E when k is also
      small, and its maximum values shift towards large values of |E| with increasing
      k. Numerical evaluations of P_{k}(E) for two different types of percolation
      clusters and the Apollonian network suggest that this observed feature might be
      generally valid.

PMID- 28505781
TI  - Statistical inference for community detection in signed networks.
AB  - The problem of community detection in networks has received wide attention and
      proves to be computationally challenging. In recent years, with the surge of
      signed networks with positive links and negative links, to find community
      structure in such signed networks has become a research focus in the area of
      network science. Although many methods have been proposed to address the problem,
      their performance seriously depends on the predefined optimization objectives or
      heuristics which are usually difficult to accurately describe the intrinsic
      structure of community. In this study, we present a statistical inference method
      for community detection in signed networks, in which a probabilistic model is
      proposed to model signed networks and the expectation-maximization-based
      parameter estimation method is deduced to find communities in signed networks. In
      addition, to efficiently analyze signed networks without any a priori
      information, a model selection criterion is also proposed to automatically
      determine the number of communities. In our experiments, the proposed method is
      tested in the synthetic and real-word signed networks and compared with current
      methods. The experimental results show the proposed method can more efficiently
      and accurately find the communities in signed networks than current methods.
      Notably, the proposed method is a mathematically principled method.

PMID- 28505782
TI  - Nonequilibrium critical dynamics of the two-dimensional Ashkin-Teller model at
      the Baxter line.
AB  - We investigate the short-time universal behavior of the two-dimensional Ashkin
      Teller model at the Baxter line by performing time-dependent Monte Carlo
      simulations. First, as preparatory results, we obtain the critical parameters by
      searching the optimal power-law decay of the magnetization. Thus, the dynamic
      critical exponents theta_{m} and theta_{p}, related to the magnetic and electric
      order parameters, as well as the persistence exponent theta_{g}, are estimated
      using heat-bath Monte Carlo simulations. In addition, we estimate the dynamic
      exponent z and the static critical exponents beta and nu for both order
      parameters. We propose a refined method to estimate the static exponents that
      considers two different averages: one that combines an internal average using
      several seeds with another, which is taken over temporal variations in the power
      laws. Moreover, we also performed the bootstrapping method for a complementary
      analysis. Our results show that the ratio beta/nu exhibits universal behavior
      along the critical line corroborating the conjecture for both magnetization and
      polarization.

PMID- 28505783
TI  - Low-frequency dielectric response of charged oblate spheroidal particles immersed
      in an electrolyte.
AB  - We study the low-frequency polarization response of a surface-charged oblate
      spheroidal particle immersed in an electrolyte solution. Because the charged
      spheroid attracts counterions which form the electric double layer around the
      particle, using usual boundary conditions at the interface between the particle
      and electrolyte can be quite complicated and challenging. Hence, we generalize
      Fixman's boundary conditions, originally derived for spherical particles, to the
      case of the charged oblate spheroid. Given two different counterion distributions
      in the thin electric double-layer limit, we obtain analytic expressions for the
      polarization coefficients to the first nontrivial order in frequency. We find
      that the polarization response normal to the symmetry axis depends on the total
      amount of charge carried by the oblate spheroid while that parallel to the
      symmetry axis is suppressed when there is less charge on the edge of the
      spheroid. We further study the overall dielectric response for a dilute
      suspension of charged spheroids. We find that the dielectric enhancement at low
      frequency, which is driven by the presence of a large zeta potential (surface
      charge), is suppressed by high ion concentrations in the electrolyte and depends
      on the size of the suspended particles. In addition, spheroids with higher aspect
      ratios will also lead to a stronger dielectric enhancement due to the combination
      of the electric double layer and textural effects. The characteristic frequency
      associated with the dielectric enhancement scales inversely with the square of
      the particle size, the major radius of the spheroid, and it has a weak dependence
      on the shape of spheroids.

PMID- 28505784
TI  - Spreading dynamics of forget-remember mechanism.
AB  - We study extensively the forget-remember mechanism (FRM) for message spreading,
      originally introduced in Eur. Phys. J. B 62, 247 (2008)EPJBFY1434
      602810.1140/epjb/e2008-00139-4. The freedom of specifying forget-remember
      functions governing the FRM can enrich the spreading dynamics to a very large
      extent. The master equation is derived for describing the FRM dynamics. By
      applying the mean field techniques, we have shown how the steady states can be
      reached under certain conditions, which agrees well with the Monte Carlo
      simulations. The distributions of forget and remember times can be explicitly
      given when the forget-remember functions take linear or exponential forms, which
      might shed some light on understanding the temporal nature of diseases like flu.
      For time-dependent FRM there is an epidemic threshold related to the FRM
      parameters. We have proven that the mean field critical transmissibility for the
      SIS model and the critical transmissibility for the SIR model are the lower and
      the the upper bounds of the critical transmissibility for the FRM model,
      respectively.

PMID- 28505785
TI  - Noise-induced polarization switching in complex networks.
AB  - The combination of bistability and noise is ubiquitous in complex systems, from
      biology to social interactions, and has important implications for their
      functioning and resilience. Here we use a simple three-state dynamical process,
      in which nodes go from one pole to another through an intermediate state, to show
      that noise can induce polarization switching in bistable systems if dynamical
      correlations are significant. In large, fully connected networks, where dynamical
      correlations can be neglected, increasing noise yields a collapse of bistability
      to an unpolarized configuration where the three possible states of the nodes are
      equally likely. In contrast, increased noise induces abrupt and irreversible
      polarization switching in sparsely connected networks. In multiplexes, where each
      layer can have a different polarization tendency, one layer is dominant and
      progressively imposes its polarization state on the other, offsetting or
      promoting the ability of noise to switch its polarization. Overall, we show that
      the interplay of noise and dynamical correlations can yield discontinuous
      transitions between extremes, which cannot be explained by a simple mean-field
      description.

PMID- 28505786
TI  - Nonequilibrium nature of adaptation in bacterial chemotaxis: A fluctuation
      dissipation theorem approach.
AB  - Adaptation is a crucial biological function possessed by many sensory systems. In
      this paper, we show that the fluctuation-dissipation theorem (FDT) serves as an
      ideal mathematical tool to study adaptation. With the aid of the nonequilibrium
      FDT developed by Seifert and Speck [Europhys. Lett. 89, 10007 (2010)EULEEJ0295
      507510.1209/0295-5075/89/10007], we demonstrate the nonequilibrium nature of
      adaptation in bacterial chemotaxis. We further show that nonequilibrium is a
      necessary condition for adaptation even beyond the linear response regime using
      the spectral theory of generator matrices. In particular, the results of this
      paper are irrelevant to the specific functional forms of the model parameters.
      This suggests that the nonequilibrium nature of adaptation is a topological
      property, rather than a geometric property, of the underlying biochemical
      reaction network.

PMID- 28505787
TI  - Heat transport along a chain of coupled quantum harmonic oscillators.
AB  - I study the heat transport properties of a chain of coupled quantum harmonic
      oscillators in contact at its ends with two heat reservoirs at distinct
      temperatures. My approach is based on the use of an evolution equation for the
      density operator which is a canonical quantization of the classical Fokker-Planck
      Kramers equation. I set up the evolution equation for the covariances and obtain
      the stationary covariances at the stationary states from which I determine the
      thermal conductance in closed form when the interparticle interaction is small.
      The conductance is finite in the thermodynamic limit implying an infinite thermal
      conductivity.

PMID- 28505789
TI  - Manipulation and amplification of the Casimir force through surface fields using
      helicity.
AB  - We present both exact and numerical results for the behavior of the Casimir force
      in O(n) systems with a finite extension L in one direction when the system is
      subjected to surface fields that induce helicity in the order parameter. We show
      that for such systems, the Casimir force in certain temperature ranges is of the
      order of L^{-2}, both above and below the critical temperature, T_{c}, of the
      bulk system. An example of such a system would be one with chemically modulated
      bounding surfaces, in which the modulation couples directly to the system's order
      parameter. We demonstrate that, depending on the parameters of the system, the
      Casimir force can be either attractive or repulsive. The exact calculations
      presented are for the one-dimensional XY and Heisenberg models under twisted
      boundary conditions resulting from finite surface fields that differ in direction
      by a specified angle, and the three-dimensional Gaussian model with surface
      fields in the form of plane waves that are shifted in phase with respect to each
      other. Additionally, we present exact and numerical results for the mean-field
      version of the three-dimensional O(2) model with finite surface fields on the
      bounding surfaces. We find that all significant results are consistent with the
      expectations of finite-size scaling.

PMID- 28505788
TI  - Flow and evolution of ice-sucrose crystal mushes.
AB  - We study the rheology of suspensions of ice crystals at moderate to high volume
      fractions in a sucrose solution in which they are partially soluble, a model
      system for a wide class of crystal mushes or slurries. Under step changes in
      shear rate, the viscosity changes to a relaxed value over several minutes, in a
      manner well fitted by a single exponential. The behavior of the relaxed viscosity
      is power-law shear thinning with shear rate, with an exponent of -1.76+/-0.25, so
      that shear stress falls with increasing shear rate. On longer time scales, the
      crystals ripen (leading to a falling viscosity) so that the mean radius increases
      with time to the power 0.14+/-0.07. We speculate that this unusually small
      exponent is due to the interaction of classical ripening dynamics with abrasion
      or breakup under flow. We compare the rheological behavior to mechanistic models
      based on flow-induced aggregation and breakup of crystal clusters, finding that
      the exponents can be predicted from liquid phase sintering and breakup by brittle
      fracture.

PMID- 28505790
TI  - Multiparticle collision simulations of two-dimensional one-component plasmas:
      Anomalous transport and dimensional crossovers.
AB  - By means of hybrid multiparticle collsion-particle-in-cell (MPC-PIC) simulations
      we study the dynamical scaling of energy and density correlations at equilibrium
      in moderately coupled two-dimensional (2D) and quasi-one-dimensional (1D)
      plasmas. We find that the predictions of nonlinear fluctuating hydrodynamics for
      the structure factors of density and energy fluctuations in 1D systems with three
      global conservation laws hold true also for 2D systems that are more extended
      along one of the two spatial dimensions. Moreover, from the analysis of the
      equilibrium energy correlators and density structure factors of both 1D and 2D
      neutral plasmas, we find that neglecting the contribution of the fluctuations of
      the vanishing self-consistent electrostatic fields overestimates the interval of
      frequencies over which the anomalous transport is observed. Such violations of
      the expected scaling in the currents correlation are found in different regimes,
      hindering the observation of the asymptotic scaling predicted by the theory.

PMID- 28505791
TI  - Driven flow with exclusion and spin-dependent transport in graphenelike
      structures.
AB  - We present a simplified description for spin-dependent electronic transport in
      honeycomb-lattice structures with spin-orbit interactions, using generalizations
      of the stochastic nonequilibrium model known as the totally asymmetric simple
      exclusion process. Mean field theory and numerical simulations are used to study
      currents, density profiles, and current polarization in quasi-one-dimensional
      systems with open boundaries, and externally imposed particle injection (alpha)
      and ejection (beta) rates. We investigate the influence of allowing for double
      site occupancy, according to Pauli's exclusion principle, on the behavior of the
      quantities of interest. We find that double occupancy shows strong signatures for
      specific combinations of rates, namely high alpha and low beta, but otherwise its
      effects are quantitatively suppressed. Comments are made on the possible
      relevance of the present results to experiments on suitably doped graphenelike
      structures.

PMID- 28505792
TI  - Deffuant model on a ring with repelling mechanism and circular opinions.
AB  - We investigate a Deffuant model on a ring by introducing two modifications: the
      repelling mechanism and the circular opinions. The repelling mechanism drives the
      opinions of two individuals away from each other and the circular opinions are
      defined on a circle. We find that the repelling mechanism tends to polarize the
      opinions of adjacent individuals and the circular opinions bring up a
      spatiotemporal pattern in which all individuals take different opinions but the
      opinion difference between two neighboring individuals tends to zero in the limit
      of the population size. In the Deffuant model with both repelling mechanism and
      the circular opinions, opinion dynamics depends on both the bounded confidence
      and the convergence rate. The interplay between the repelling mechanism and the
      circular opinion may give rise to time-dependent opinion dynamics.

PMID- 28505793
TI  - Publisher's Note: Dynamics and thermodynamics of systems with long-range dipole
      type interactions [Phys. Rev. E 95, 022110 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.95.022110.

PMID- 28505794
TI  - How to desynchronize quorum-sensing networks.
AB  - In this paper we investigate how so-called quorum-sensing networks can be
      desynchronized. Such networks, which arise in many important application fields,
      such as systems biology, are characterized by the fact that direct communication
      between network nodes is superimposed to communication with a shared,
      environmental variable. In particular, we provide a new sufficient condition
      ensuring that the trajectories of these quorum-sensing networks diverge from
      their synchronous evolution. Then, we apply our result to study two applications.

PMID- 28505795
TI  - Parallelization of microfluidic flow-focusing devices.
AB  - Microfluidic flow-focusing devices offer excellent control over fluid flow,
      enabling formation of drops with a narrow size distribution. However, the
      throughput of microfluidic flow-focusing devices is limited and scale-up through
      operation of multiple drop makers in parallel often compromises the robustness of
      their operation. We demonstrate that parallelization is facilitated if the outer
      phase is injected from the direction opposite to that of the inner phase, because
      the fluid injection flow rate, where the drop formation transitions from the
      squeezing into the dripping regime, is shifted towards higher values.

PMID- 28505796
TI  - Effects of a local defect on one-dimensional nonlinear surface growth.
AB  - The slow-bond problem is a long-standing question about the minimal strength
      epsilon_{c} of a local defect with global effects on the Kardar-Parisi-Zhang
      (KPZ) universality class. A consensus on the issue has been delayed due to the
      discrepancy between various analytical predictions claiming epsilon_{c}=0 and
      numerical observations claiming epsilon_{c}>0. We revisit the problem via finite
      size scaling analyses of the slow-bond effects, which are tested for different
      boundary conditions through extensive Monte Carlo simulations. Our results
      provide evidence that the previously reported nonzero epsilon_{c} is an artifact
      of a crossover phenomenon which logarithmically converges to zero as the system
      size goes to infinity.

PMID- 28505797
TI  - Metastable memristive lines for signal transmission and information processing
      applications.
AB  - Traditional studies of memristive devices have mainly focused on their
      applications in nonvolatile information storage and information processing. Here,
      we demonstrate that the third fundamental component of information technologies
      the transfer of information-can also be employed with memristive devices. For
      this purpose, we introduce a metastable memristive circuit. Combining metastable
      memristive circuits into a line, one obtains an architecture capable of
      transferring a signal edge from one space location to another. We emphasize that
      the suggested metastable memristive lines employ only resistive circuit
      components. Moreover, their networks (for example, Y-connected lines) have an
      information processing capability.

PMID- 28505798
TI  - Modeling intra- and intermolecular correlations for linear and branched polymers
      using a modified test-chain self-consistent field theory.
AB  - A modified test-chain self-consistent field theory (SCFT) is presented to study
      the intra- and intermolecular correlations of linear and branched polymers in
      various solutions and melts. The key to the test-chain SCFT is to break the the
      translational symmetry by fixing a monomer at the origin of a coordinate. This
      theory successfully describes the crossover from self-avoiding walk at short
      distances to screened random walk at long distances in a semidilute solution or
      melt. The calculations indicated that branching enhances the swelling of polymers
      in melts and influences stretching at short distances. The test-chain SCFT
      calculations show good agreement with experiments and classic polymer theories.
      We highlight that the theory presented here provides a solution to interpret the
      polymer conformation and behavior under various conditions within the framework
      of one theory.

PMID- 28505799
TI  - Soliton excitations on a continuous-wave background in the modulational
      instability regime with fourth-order effects.
AB  - We study the correspondence between modulational instability and types of
      fundamental nonlinear excitation in a nonlinear fiber with both third-order and
      fourth-order effects. Some soliton excitations are obtained in the modulational
      instability regime which have not been found in nonlinear fibers with second
      order effects and third-order effects. Explicit analysis suggests that the
      existence of solitons is related to the modulation stability circle in the
      modulation instability regime, and they just exist in the modulational
      instability regime outside of the modulational stability circle. It should be
      emphasized that the solitons exist only with two special profiles on a continuous
      wave background at a certain frequency. The evolution stability of the solitons
      is tested numerically by adding some noise to initial states, which indicates
      that they are robust against perturbations even in the modulation instability
      regime. Further analysis indicates that solitons in the modulational instability
      regime are caused by fourth-order effects.

PMID- 28505800
TI  - Kramers problem for a dimer: Effect of noise correlations.
AB  - The Kramers problem for a dimer in a bistable piecewise linear potential is
      studied in the presence of correlated noise processes. The effect of such a
      correlation is to redistribute the thermal power between the dynamical degrees of
      freedom, and this leads to significant deviations in the dynamics of the system
      from the case of independent noise processes. The distribution of first passage
      times from one minima to the basin of attraction of the other minima is found to
      have exponentially decaying tails with the parameter dependent on the amount of
      correlation and the coupling between the particles. The strong coupling limit of
      the problem is analyzed using adiabatic elimination, where it is found that the
      initial probability density relaxes towards a stationary value on the same time
      scale as the mean escape time when the noise intensity of the system is low. For
      higher noise fluctuations, the relaxation towards the stationary state is slower
      in comparison to escape times. In the extreme limit of perfect anticorrelation,
      the random dynamical system behaves as a deterministic system in a steady state
      in which the center of mass starting from the unstable maxima moves down the hill
      and gets trapped in the potential minima. The implications for polymer dynamics
      in a potential are discussed.

PMID- 28505801
TI  - Finite-size scaling in the Kuramoto model.
AB  - We investigate the scaling properties of the order parameter and the largest
      nonvanishing Lyapunov exponent for the fully locked state in the Kuramoto model
      with a finite number N of oscillators. We show that, for any finite value of N,
      both quantities scale as (K-K_{L})^{1/2} with the coupling strength K
      sufficiently close to the locking threshold K_{L}. We confirm numerically these
      predictions for oscillator frequencies evenly spaced in the interval [-1,1] and
      additionally find that the coupling range deltaK over which this scaling is valid
      shrinks like deltaK~N^{-alpha} with alpha~1.5 as N->infinity. Away from this
      interval, the order parameter exhibits the infinite-N behavior r-r_{L}~(K
      K_{L})^{2/3} proposed by Pazo [Phys. Rev. E 72, 046211 (2005)]PLEEE81539
      375510.1103/PhysRevE.72.046211. We argue that the crossover between the two
      behaviors occurs because at the locking threshold, the upper bound of the
      continuous part of the spectrum of the fully locked state approaches zero as N
      increases. Our results clarify the convergence to the N->infinity limit in the
      Kuramoto model.

PMID- 28505802
TI  - Embryonic metabolism of the ornithischian dinosaurs Protoceratops andrewsi and
      Hypacrosaurus stebingeri and implications for calculations of dinosaur egg
      incubation times.
AB  - The embryonic metabolisms of the ornithischian dinosaurs Protoceratops andrewsi
      and Hypacrosaurus stebingeri have been determined and are in the range observed
      in extant reptiles. The average value of the measured embryonic metabolic rates
      for P. andrewsi and H. stebingeri are then used to calculate the incubation times
      for 21 dinosaurs from both Sauischia and Ornithischia using a mass growth model
      based on conservation of energy. The calculated incubation times vary from about
      70 days for Archaeopteryx lithographica to about 180 days for Alamosaurus
      sanjuanensis. Such long incubation times seem unlikely, particularly for the
      sauropods and large theropods. Incubation times are also predicted with the
      assumption that the saurischian dinosaurs had embryonic metabolisms in the range
      observed in extant birds.

PMID- 28505803
TI  - Simulating competitive egress of noncircular pedestrians.
AB  - We present a numerical framework to simulate pedestrian dynamics in highly
      competitive conditions by means of a force-based model implemented with
      spherocylindrical particles instead of the traditional, symmetric disks. This
      modification of the individuals' shape allows one to naturally reproduce recent
      experimental findings of room evacuations through narrow doors in situations
      where the contact pressure among the pedestrians was rather large. In particular,
      we obtain a power-law tail distribution of the time lapses between the passage of
      consecutive individuals. In addition, we show that this improvement leads to new
      features where the particles' rotation acquires great significance.

PMID- 28505804
TI  - Gauge-free cluster variational method by maximal messages and moment matching.
AB  - We present an implementation of the cluster variational method (CVM) as a message
      passing algorithm. The kind of message passing algorithm used for CVM, usually
      named generalized belief propagation (GBP), is a generalization of the belief
      propagation algorithm in the same way that CVM is a generalization of the Bethe
      approximation for estimating the partition function. However, the connection
      between fixed points of GBP and the extremal points of the CVM free energy is
      usually not a one-to-one correspondence because of the existence of a gauge
      transformation involving the GBP messages. Our contribution is twofold. First, we
      propose a way of defining messages (fields) in a generic CVM approximation, such
      that messages arrive on a given region from all its ancestors, and not only from
      its direct parents, as in the standard parent-to-child GBP. We call this approach
      maximal messages. Second, we focus on the case of binary variables,
      reinterpreting the messages as fields enforcing the consistency between the
      moments of the local (marginal) probability distributions. We provide a precise
      rule to enforce all consistencies, avoiding any redundancy, that would otherwise
      lead to a gauge transformation on the messages. This moment matching method is
      gauge free, i.e., it guarantees that the resulting GBP is not gauge invariant. We
      apply our maximal messages and moment matching GBP to obtain an analytical
      expression for the critical temperature of the Ising model in general dimensions
      at the level of plaquette CVM. The values obtained outperform Bethe estimates,
      and are comparable with loop corrected belief propagation equations. The method
      allows for a straightforward generalization to disordered systems.

PMID- 28505805
TI  - Hysteresis in relative permeabilities suffices for propagation of saturation
      overshoot: A quantitative comparison with experiment.
AB  - Traditional Darcy theory for two-phase flow in porous media is shown to predict
      the propagation of nonmonotone saturation profiles, also known as saturation
      overshoot. The phenomenon depends sensitively on the constitutive parameters, on
      initial conditions, and on boundary conditions. Hysteresis in relative
      permeabilities is needed to observe the effect. Two hysteresis models are
      discussed and compared. The shape of overshoot solutions can change as a function
      of time or remain fixed and time independent. Traveling-wave-like overshoot
      profiles of fixed width exist in experimentally accessible regions of parameter
      space. They are compared quantitatively against experiment.

PMID- 28505806
TI  - Kinetic discrimination of a polymerase in the presence of obstacles.
AB  - One of the causes of high fidelity of copying in biological systems is kinetic
      discrimination. In this mechanism larger dissipation and copying velocity result
      in improved copying accuracy. We consider a model of a polymerase which
      simultaneously copies a single-stranded RNA and opens a single- to double
      stranded junction serving as an obstacle. The presence of the obstacle slows down
      the motor, resulting in a change of its fidelity, which can be used to gain
      information about the motor and junction dynamics. We find that the motor's
      fidelity does not depend on details of the motor-junction interaction, such as
      whether the interaction is passive or active. Analysis of the copying fidelity
      can still be used as a tool for investigating the junction kinetics.

PMID- 28505807
TI  - Effect of fractional blood flow on plasma skimming in the microvasculature.
AB  - Although redistribution of red blood cells at bifurcated vessels is highly
      dependent on flow rate, it is still challenging to quantitatively express the
      dependence of flow rate in plasma skimming due to nonlinear cellular
      interactions. We suggest a plasma skimming model that can involve the effect of
      fractional blood flow at each bifurcation point. To validate the model, it is
      compared with in vivo data at single bifurcation points, as well as microvascular
      network systems. In the simulation results, the exponential decay of the plasma
      skimming parameter M along fractional flow rate shows the best performance in
      both cases.

PMID- 28505808
TI  - Publisher's Note: Effect of the salt-induced micellar microstructure on the
      nonlinear shear flow behavior of ionic cetylpyridinium chloride surfactant
      solutions [Phys. Rev. E 95, 032603 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.95.032603.

PMID- 28505809
TI  - Dissociation rates from single-molecule pulling experiments under large thermal
      fluctuations or large applied force.
AB  - Theories that are used to extract energy-landscape information from single
      molecule pulling experiments in biophysics are all invariably based on Kramers'
      theory of the thermally activated escape rate from a potential well. As is well
      known, this theory recovers the Arrhenius dependence of the rate on the barrier
      energy and crucially relies on the assumption that the barrier energy is much
      larger than k_{B}T (limit of comparatively low thermal fluctuations). As was
      shown already in Dudko et al. [Phys. Rev. Lett. 96, 108101 (2006)PRLTAO0031
      900710.1103/PhysRevLett.96.108101], this approach leads to the unphysical
      prediction of dissociation time increasing with decreasing binding energy when
      the latter is lowered to values comparable to k_{B}T (limit of large thermal
      fluctuations). We propose a theoretical framework (fully supported by numerical
      simulations) which amends Kramers' theory in this limit and use it to extract the
      dissociation rate from single-molecule experiments where now predictions are
      physically meaningful and in agreement with simulations over the whole range of
      applied forces (binding energies). These results are expected to be relevant for
      a large number of experimental settings in single-molecule biophysics.

PMID- 28505810
TI  - Effect of composition and pressure on the shear strength of sodium silicate
      glasses: An atomic scale simulation study.
AB  - The elastoplastic behavior of sodium silicate glasses is studied at different
      scales as a function of composition and pressure, with the help of quasistatic
      atomistic simulations. The samples are first compressed and then sheared at
      constant pressure to calculate yield strength and permanent plastic deformations.
      Changes occurring in the global response are then compared to the analysis of
      local plastic rearrangements and strain heterogeneities. It is shown that the
      plastic response results from the succession of well-identified localized
      irreversible deformations occurring in a nanometer-size area. The size and the
      number of these local rearrangements, as well as the amount of internal
      deviatoric and volumetric plastic deformation, are sensitive to the composition
      and to the pressure. In the early stages of the deformation, plastic
      rearrangements are driven by sodium mobility. Consequently, the elastic yield
      strength decreases when the sodium content increases, and the same when pressure
      increases. Finally, good correlation was found between global and local stress
      strain relationships, reinforcing again the role of sodium ions as local
      initiators of the plastic behavior observed at larger scales.

PMID- 28505811
TI  - Chaotic Lagrangian models for turbulent relative dispersion.
AB  - A deterministic multiscale dynamical system is introduced and discussed as a
      prototype model for relative dispersion in stationary, homogeneous, and isotropic
      turbulence. Unlike stochastic diffusion models, here trajectory transport and
      mixing properties are entirely controlled by Lagrangian chaos. The anomalous
      "sweeping effect," a known drawback common to kinematic simulations, is removed
      through the use of quasi-Lagrangian coordinates. Lagrangian dispersion statistics
      of the model are accurately analyzed by computing the finite-scale Lyapunov
      exponent (FSLE), which is the optimal measure of the scaling properties of
      dispersion. FSLE scaling exponents provide a severe test to decide whether model
      simulations are in agreement with theoretical expectations and/or observation.
      The results of our numerical experiments cover a wide range of "Reynolds numbers"
      and show that chaotic deterministic flows can be very efficient, and numerically
      low-cost, models of turbulent trajectories in stationary, homogeneous, and
      isotropic conditions. The mathematics of the model is relatively simple, and, in
      a geophysical context, potential applications may regard small-scale
      parametrization issues in general circulation models, mixed layer, and/or
      boundary layer turbulence models as well as Lagrangian predictability studies.

PMID- 28505812
TI  - Transient exchange fluctuation theorems for heat using a Hamiltonian framework:
      Classical and quantum regimes.
AB  - We investigate the statistics of heat exchange between a finite system coupled to
      reservoir(s). We have obtained analytical results for heat fluctuation theorems
      in the transient regime considering the Hamiltonian dynamics of the composite
      system consisting of the system of interest and the heat bath(s). The system of
      interest is driven by an external protocol. We first derive it in the context of
      a single heat bath. The result is in exact agreement with known result. We then
      generalize the treatment to two heat baths. We further extend the study to
      quantum systems and show that relations similar to the classical case hold in the
      quantum regime. For our study we invoke von Neumann two-point projective
      measurement in quantum mechanics in the transient regime. The study of quantum
      systems follows the same lines of argument as that of the classical system, and
      as a result the treatment used in the latter complements that used in the former.
      Our result is a generalization of Jarzynski-Wojcik heat fluctuation theorem.

PMID- 28505814
TI  - Optimal detrended fluctuation analysis as a tool for the determination of the
      roughness exponent of the mounded surfaces.
AB  - We present an optimal detrended fluctuation analysis (DFA) and apply it to
      evaluate the local roughness exponent in nonequilibrium surface growth models
      with mounded morphology. Our method consists in analyzing the height fluctuations
      computing the shortest distance of each point of the profile to a detrending
      curve that fits the surface within the investigated interval. We compare the
      optimal DFA (ODFA) with both the standard DFA and nondetrended analysis. We
      validate the ODFA method considering a one-dimensional model in the Kardar-Parisi
      Zhang universality class starting from a mounded initial condition. We applied
      the methods to the Clarke-Vvedensky (CV) model in 2+1 dimensions with thermally
      activated surface diffusion and absence of step barriers. It is expected that
      this model belongs to the nonlinear molecular beam epitaxy (nMBE) universality
      class. However, an explicit observation of the roughness exponent in agreement
      with the nMBE class was still missing. The effective roughness exponent obtained
      with ODFA agrees with the value expected for the nMBE class, whereas using the
      other methods it does not agree. We also characterize the transient anomalous
      scaling of the CV model and obtained that the corresponding exponent is in
      agreement with the value reported for other nMBE models with weaker corrections
      to the scaling.

PMID- 28505813
TI  - Devil's staircase continuum in the chiral clock spin glass with competing
      ferromagnetic-antiferromagnetic and left-right chiral interactions.
AB  - The chiral clock spin-glass model with q=5 states, with both competing
      ferromagnetic-antiferromagnetic and left-right chiral frustrations, is studied in
      d=3 spatial dimensions by renormalization-group theory. The global phase diagram
      is calculated in temperature, antiferromagnetic bond concentration p, random
      chirality strength, and right-chirality concentration c. The system has a
      ferromagnetic phase, a multitude of different chiral phases, a chiral spin-glass
      phase, and a critical (algebraically) ordered phase. The ferromagnetic and chiral
      phases accumulate at the disordered phase boundary and form a spectrum of devil's
      staircases, where different ordered phases characteristically intercede at all
      scales of phase-diagram space. Shallow and deep reentrances of the disordered
      phase, bordered by fragments of regular and temperature-inverted devil's
      staircases, are seen. The extremely rich phase diagrams are presented as
      continuously and qualitatively changing videos.

PMID- 28505815
TI  - Interaction of toroidal swimmers in Stokes flow.
AB  - A doughnut-shaped object supporting surface rotations was a hypothetical
      construct proposed by both Taylor and Purcell as a swimmer that would be able to
      propel itself in a Stokesian fluid because of the irreversibility of its stroke.
      Here we numerically examine the hydrodynamic interaction of pairs and trios of
      these free toroidal swimmers. First, we study the axisymmetric case of two
      toroidal swimmers placed in tandem, and show that a single torus of a corotating
      pair is more efficient than when it swims alone, but less efficient when paired
      with a counterrotating partner. Using a regularized Stokeslet framework, we study
      the nonaxisymmetric case of toroidal swimmers whose axes are initially parallel,
      but not collinear. These perturbed in tandem swimmers can exhibit qualitatively
      different trajectories that may, for instance, repel the swimmers or have them
      settle into a periodic state. We also illustrate interesting dynamics that occur
      for different initial configurations of three tori.

PMID- 28505816
TI  - Minimum energetic cost to maintain a target nonequilibrium state.
AB  - In the absence of external driving, a system exposed to thermal fluctuations will
      relax to equilibrium. However, the constant input of work makes it possible to
      counteract this relaxation and maintain the system in a nonequilibrium steady
      state. In this article, we use the stochastic thermodynamics of Markov jump
      processes to compute the minimum rate at which energy must be supplied and
      dissipated to maintain an arbitrary nonequilibrium distribution in a given energy
      landscape. This lower bound depends on two factors: the undriven probability
      current in the equilibrium state and the distance from thermal equilibrium of the
      target distribution. By showing the consequences of this result in a few simple
      examples, we suggest general implications for the required energetic costs of
      macromolecular repair and cytosolic protein localization.

PMID- 28505817
TI  - Fractal dimension and universality in avascular tumor growth.
AB  - For years, the comprehension of the tumor growth process has been intriguing
      scientists. New research has been constantly required to better understand the
      complexity of this phenomenon. In this paper, we propose a mathematical model
      that describes the properties, already known empirically, of avascular tumor
      growth. We present, from an individual-level (microscopic) framework, an
      explanation of some phenomenological (macroscopic) aspects of tumors, such as
      their spatial form and the way they develop. Our approach is based on competitive
      interaction between the cells. This simple rule makes the model able to reproduce
      evidence observed in real tumors, such as exponential growth in their early stage
      followed by power-law growth. The model also reproduces (i) the fractal-space
      distribution of tumor cells and (ii) the universal growth behavior observed in
      both animals and tumors. Our analyses suggest that the universal similarity
      between tumor and animal growth comes from the fact that both can be described by
      the same dynamic equation-the Bertalanffy-Richards model-even if they do not
      necessarily share the same biological properties.

PMID- 28505818
TI  - Anomalous temperature-dependent heat transport in one-dimensional momentum
      conserving systems with soft-type interparticle interaction.
AB  - We numerically investigate the heat transport problem in a one-dimensional
      momentum-conserving lattice with a soft-type (ST) anharmonic interparticle
      interaction. It is found that with the increase of the system's temperature,
      while the introduction of ST anharmonicity softens phonons and decreases their
      velocities, this type of nonlinearity like its hard type (HT) counterpart, can
      still not be able to fully damp the longest wavelength phonons. Therefore, a
      usual anomalous temperature dependence of heat transport with certain scaling
      properties similarly to those shown in the Fermi-Pasta-Ulam-beta-like systems
      with HT interactions can be seen. Our detailed examination from simulations
      verifies this temperature-dependent behavior well.

PMID- 28505819
TI  - Size dependence of static polymer droplet behavior from many-body dissipative
      particle dynamics simulation.
AB  - We used molecular simulation to study the static behavior of polymer droplets in
      vacuum and on solid surfaces, namely the size of the droplet and the contact
      angle, respectively. The effects of the polymer chain length and the total number
      of particles were calculated by the many-body dissipative particle dynamics
      method. For the spherical droplet containing the same number of particles, we
      show that its radius depends on the polymer chain length. The radius of the
      droplet is also proportional to one-third power of the total number of particles
      for all given chain lengths. For the hemispherical droplet, the contact angle
      increases with the number of particles in the droplet, and this effect is
      relatively strong, especially for longer polymer chains. The effect of
      wettability of the solid surface was also investigated by using polymerphobic
      (low-affinity) and polymerphilic (high-affinity) surfaces. As the chain length
      increases, the contact angle on the low-affinity surface decreases, while that on
      the hydrophilic surface increases. The simulation reveals that there is a
      critical affinity for the monomer on the solid surface; above and below which the
      wettability increases and decreases as the molecular length increases,
      respectively.

PMID- 28505820
TI  - Robustness of free and pinned spiral waves against breakup by electrical forcing
      in excitable chemical media.
AB  - We present an investigation on the breakup of free and pinned spiral waves under
      an applied electrical current in the Belousov-Zhabotinsky reaction. Spiral fronts
      propagating towards the negative electrode are decelerated. A breakup of the
      spiral waves occurs when some segments of the fronts are stopped by a
      sufficiently strong electrical current. In the absence of obstacles (i.e., free
      spiral waves), the critical value of the electrical current for the wave breakup
      increases with the excitability of the medium. For spiral waves pinned to
      circular obstacles, the critical electrical current increases with the obstacle
      diameter. Analysis of spiral dynamics shows that the enhancement of the
      robustness against the breakup of both free and pinned spiral waves is originated
      by the increment of wave speed when either the excitability is strengthened or
      the obstacle size is enlarged. The experimental findings are reproduced by
      numerical simulations using the Oregonator model. In addition, the simulations
      reveal that the robustness against the forced breakup increases with the
      activator level in both cases of free and pinned spiral waves.

PMID- 28505821
TI  - Stable swarming using adaptive long-range interactions.
AB  - Sensory mechanisms in biology, from cells to humans, have the property of
      adaptivity, whereby the response produced by the sensor is adapted to the overall
      amplitude of the signal, reducing the sensitivity in the presence of strong
      stimulus, while increasing it when it is weak. This property is inherently energy
      consuming and a manifestation of the nonequilibrium nature of living organisms.
      We explore here how adaptivity affects the effective forces that organisms feel
      due to others in the context of a uniform swarm, in both two and three
      dimensions. The interactions between the individuals are taken to be attractive
      and long-range and of power-law form. We find that the effects of adaptivity
      inside the swarm are dramatic, where the effective forces decrease (or remain
      constant) with increasing swarm density. Linear stability analysis demonstrates
      how this property prevents collapse (Jeans instability), when the forces are
      adaptive. Adaptivity therefore endows swarms with a natural mechanism for self
      stabilization.

PMID- 28505822
TI  - Symmetry breaking by heating in a continuous opinion model.
AB  - We study the critical behavior of a continuous opinion model, driven by kinetic
      exchanges in a fully connected population. Opinions range in the real interval [
      1,1], representing the different shades of opinions against and for an issue
      under debate. Individuals' opinions evolve through pairwise interactions, with
      couplings that are typically positive, but a fraction p of negative ones is
      allowed. Moreover, a social temperature parameter T controls the tendency of the
      individual responses toward neutrality. Depending on p and T, different
      collective states emerge: symmetry broken (one side wins), symmetric (tie of
      opposite sides), and absorbing neutral (indecision wins). We find the critical
      points and exponents that characterize the phase transitions between them. The
      symmetry breaking transition belongs to the usual Ising mean-field universality
      class, but the absorbing-phase transitions, with beta=0.5, are out of the
      paradigmatic directed percolation class. Moreover, ordered phases can emerge by
      increasing social temperature.

PMID- 28505823
TI  - Effect of internal mass in the lattice Boltzmann simulation of moving solid
      bodies by the smoothed-profile method.
AB  - A computational method for the simulation of particulate flows that can
      efficiently treat the particle-fluid boundary in systems containing many
      particles was developed based on the smoothed-profile lattice Boltzmann method
      (SPLBM). In our proposed method, which we call the improved SPLBM (iSPLBM), for
      an accurate and stable simulation of particulate flows, the hydrodynamic force on
      a moving solid particle is exactly formulated with consideration of the effect of
      internal fluid mass. To validate the accuracy and stability of iSPLBM, we
      conducted numerical simulations of several particulate flow systems and compared
      our results with those of other simulations and some experiments. In addition, we
      performed simulations on flotation of many lightweight particles with a wide
      range of particle size distribution, the results of which demonstrated the
      effectiveness of iSPLBM. Our proposed model is a promising method to accurately
      and stably simulate extensive particulate flows.

PMID- 28505824
TI  - Classification framework for partially observed dynamical systems.
AB  - We present a general framework for classifying partially observed dynamical
      systems based on the idea of learning in the model space. In contrast to the
      existing approaches using point estimates of model parameters to represent
      individual data items, we employ posterior distributions over model parameters,
      thus taking into account in a principled manner the uncertainty due to both the
      generative (observational and/or dynamic noise) and observation (sampling in
      time) processes. We evaluate the framework on two test beds: a biological pathway
      model and a stochastic double-well system. Crucially, we show that the
      classification performance is not impaired when the model structure used for
      inferring posterior distributions is much more simple than the observation
      generating model structure, provided the reduced-complexity inferential model
      structure captures the essential characteristics needed for the given
      classification task.

PMID- 28505825
TI  - First-principles simulations of warm dense lithium fluoride.
AB  - We perform first-principles path integral Monte Carlo (PIMC) and density
      functional theory molecular dynamics (DFT-MD) calculations to explore warm dense
      matter states of LiF. Our simulations cover a wide density-temperature range of
      2.08-15.70gcm^{-3} and 10^{4}-10^{9} K. Since PIMC and DFT-MD accurately treat
      effects of atomic shell structure, we find a pronounced compression maximum and a
      shoulder on the principal Hugoniot curve attributed to K-shell and L-shell
      ionization. The results provide a benchmark for widely used EOS tables, such as
      SESAME, LEOS, and models. In addition, we compute pair-correlation functions that
      reveal an evolving plasma structure and ionization process that is driven by
      thermal and pressure ionization. Finally, we compute electronic density of states
      of liquid LiF from DFT-MD simulations and find that the electronic gap can remain
      open with increasing density and temperature to at least 15.7 gcm^{-3}.

PMID- 28505826
TI  - Steepest-entropy-ascent nonequilibrium quantum thermodynamic framework to model
      chemical reaction rates at an atomistic level.
AB  - The steepest entropy ascent (SEA) dynamical principle provides a general
      framework for modeling the dynamics of nonequilibrium (NE) phenomena at any level
      of description, including the atomistic one. It has recently been shown to
      provide a precise implementation and meaning to the maximum entropy production
      principle and to encompass many well-established theories of nonequilibrium
      thermodynamics into a single unifying geometrical framework. Its original
      formulation in the framework of quantum thermodynamics (QT) assumes the simplest
      and most natural Fisher-Rao metric to geometrize from a dynamical standpoint the
      manifold of density operators, which represent the thermodynamic NE states of the
      system. This simplest SEAQT formulation is used here to develop a general
      mathematical framework for modeling the NE time evolution of the quantum state of
      a chemically reactive mixture at an atomistic level. The method is illustrated
      for a simple two-reaction kinetic scheme of the overall reaction F+H_{2}<=>HF+F
      in an isolated tank of fixed volume. However, the general formalism is developed
      for a reactive system subject to multiple reaction mechanisms. To explicitly
      implement the SEAQT nonlinear law of evolution for the density operator, both the
      energy and the particle number eigenvalue problems are set up and solved
      analytically under the dilute gas approximation. The system-level energy and
      particle number eigenvalues and eigenstates are used in the SEAQT equation of
      motion to determine the time evolution of the density operator, thus effectively
      describing the overall kinetics of the reacting system as it relaxes toward
      stable chemical equilibrium. The predicted time evolution in the near-equilibrium
      limit is compared to the reaction rates given by a standard detailed kinetic
      model so as to extract the single time constant needed by the present SEA model.

PMID- 28505827
TI  - Intermittent feedback induces attractor selection.
AB  - We present a method for attractor selection in multistable dynamical systems. It
      involves a feedback term that is active only when the dynamics of the system is
      in a particular fraction of state space of the attractor. We implement this
      method first on a simplest symmetric chaotic flow and then on a bistable neuronal
      system. We find that adding this space-dependent feedback term to the dynamical
      equations of these systems will drive the dynamics to the desired attractor by
      annihilating the other. We further demonstrate that the attractor selection due
      to this feedback term can be used in construction of logic gates, which is one of
      the practical applications of the proposed method.

PMID- 28505828
TI  - Applications of the first digit law to measure correlations.
AB  - The quasiempirical Benford law predicts that the distribution of the first
      significant digit of random numbers obtained from mixed probability distributions
      is surprisingly meaningful and reveals some universal behavior. We generalize
      this finding to examine the joint first-digit probability of a pair of two random
      numbers and show that undetectable correlations by means of the usual covariance
      based measure can be identified in the statistics of the corresponding first
      digits. We illustrate this new measure by analyzing the correlations and
      anticorrelations of the positions of two interacting particles in their quantum
      mechanical ground state. This suggests that by using this measure, the presence
      or absence of correlations can be determined even if only the first digit of
      noisy experimental data can be measured accurately.

PMID- 28505829
TI  - Control of amplitude chimeras by time delay in oscillator networks.
AB  - We investigate the influence of time-delayed coupling in a ring network of
      nonlocally coupled Stuart-Landau oscillators upon chimera states, i.e., space
      time patterns with coexisting partially coherent and partially incoherent
      domains. We focus on amplitude chimeras, which exhibit incoherent behavior with
      respect to the amplitude rather than the phase and are transient patterns, and we
      show that their lifetime can be significantly enhanced by coupling delay. To
      characterize their transition to phase-lag synchronization (coherent traveling
      waves) and other coherent structures, we generalize the Kuramoto order parameter.
      Contrasting the results for instantaneous coupling with those for constant
      coupling delay, for time-varying delay, and for distributed-delay coupling, we
      demonstrate that the lifetime of amplitude chimera states and related partially
      incoherent states can be controlled, i.e., deliberately reduced or increased,
      depending upon the type of coupling delay.

PMID- 28505830
TI  - Modeling and statistical analysis of non-Gaussian random fields with heavy-tailed
      distributions.
AB  - In this paper, we investigate and develop an alternative approach to the
      numerical analysis and characterization of random fluctuations with the heavy
      tailed probability distribution function (PDF), such as turbulent heat flow and
      solar flare fluctuations. We identify the heavy-tailed random fluctuations based
      on the scaling properties of the tail exponent of the PDF, power-law growth of
      qth order correlation function, and the self-similar properties of the contour
      lines in two-dimensional random fields. Moreover, this work leads to a
      substitution for the fractional Edwards-Wilkinson (EW) equation that works in the
      presence of MU-stable Levy noise. Our proposed model explains the configuration
      dynamics of the systems with heavy-tailed correlated random fluctuations. We also
      present an alternative solution to the fractional EW equation in the presence of
      MU-stable Levy noise in the steady state, which is implemented numerically, using
      the MU-stable fractional Levy motion. Based on the analysis of the self-similar
      properties of contour loops, we numerically show that the scaling properties of
      contour loop ensembles can qualitatively and quantitatively distinguish non
      Gaussian random fields from Gaussian random fluctuations.

PMID- 28505831
TI  - Fast-switching chiral nematic liquid-crystal mode with polymer-sustained twisted
      vertical alignment.
AB  - We demonstrate a fast-switching liquid-crystal mode with polymer-sustained
      twisted vertical alignment. By optimizing the polymerization condition, a polymer
      microstructure with controlled orientation is produced. The polymer
      microstructure not only synergistically suppresses the optical bounce during
      field-induced homeotropic-twist transition but also shortens the response time
      significantly. Theoretical analyses validate that the ground state free energy
      density is modified by the aligning field of the polymer microstructure, which
      affects the driving voltage of the device. The outcomes of this paper will enable
      the development of fast-switching and achromatic electro-optical and photonic
      devices.

PMID- 28505832
TI  - Analysis of force treatment in the pseudopotential lattice Boltzmann equation
      method.
AB  - In this paper, different force treatments are analyzed in detail for a
      pseudopotential lattice Boltzmann equation (LBE), and the contribution of third
      order error terms to pressure tensor with a force scheme is analyzed by a higher
      order Chapman-Enskog expansion technique. From the theoretical analysis, the
      performance of the original force treatment of Shan-Chen (SC), Ladd, Guo et al.,
      and the exact difference method (EDM) are E_{Ladd}<E_{Guo}<E_{EDM}<=E_{SC} with
      the relaxation time tau>=1, while E_{Ladd}<E_{Guo}<E_{SC}<E_{EDM} with tau<1;
      here E is a parameter related to the mechanical stability and the subscripts are
      the corresponding force scheme. To be consistent with the thermodynamic theory, a
      force term is introduced to modify the coefficients in the pressure tensor. Some
      numerical simulations are conducted to show that the predictions of modified
      force treatment of the pseudopotential LBE are all in good agreement with the
      analytical solution and other predictions.

PMID- 28505833
TI  - Percolation in three-dimensional fracture networks for arbitrary size and shape
      distributions.
AB  - The percolation threshold of fracture networks is investigated by extensive
      direct numerical simulations. The fractures are randomly located and oriented in
      three-dimensional space. A very wide range of regular, irregular, and random
      fracture shapes is considered, in monodisperse or polydisperse networks
      containing fractures with different shapes and/or sizes. The results are
      rationalized in terms of a dimensionless density. A simple model involving a new
      shape factor is proposed, which accounts very efficiently for the influence of
      the fracture shape. It applies with very good accuracy in monodisperse or
      moderately polydisperse networks, and provides a good first estimation in other
      situations. A polydispersity index is shown to control the need for a correction,
      and the corrective term is modelled for the investigated size distributions.

PMID- 28505834
TI  - Dynamic phases, clustering, and chain formation for driven disk systems in the
      presence of quenched disorder.
AB  - We numerically examine the dynamic phases and pattern formation of two
      dimensional monodisperse repulsive disks driven over random quenched disorder. We
      show that there is a series of distinct dynamic regimes as a function of
      increasing drive, including a clogged or pile-up phase near depinning, a
      homogeneous disordered flow state, and a dynamically phase separated regime
      consisting of high-density crystalline regions surrounded by a low density of
      disordered disks. At the highest drives the disks arrange into one-dimensional
      moving chains. The phase separated regime has parallels with the phase separation
      observed in active matter systems, but arises from a distinct mechanism
      consisting of the combination of nonequilibrium fluctuations with density
      dependent mobility. We discuss the pronounced differences between this system and
      previous studies of driven particles with longer-range repulsive interactions
      moving over random substrates, such as superconducting vortices or electron
      crystals, where dynamical phase separation and distinct one-dimensional moving
      chains are not observed. Our results should be generic to a broad class of
      systems in which the particle-particle interactions are short ranged, such as
      sterically interacting colloids or Yukawa particles with strong screening driven
      over random pinning arrays, superconducting vortices in the limit of small
      penetration depths, or quasi-two-dimensional granular matter flowing over rough
      landscapes.

PMID- 28505835
TI  - Self-organization of charged particles in circular geometry.
AB  - The basic principles of self-organization of one-component charged particles,
      confined in disk and circular parabolic potentials, are proposed. A system of
      equations is derived, which allows us to determine equilibrium configurations for
      an arbitrary, but finite, number of charged particles that are distributed over
      several rings. Our approach reduces significantly the computational effort in
      minimizing the energy of equilibrium configurations and demonstrates a remarkable
      agreement with the values provided by molecular dynamics calculations. With the
      increase of particle number n>180 we find a steady formation of a centered
      hexagonal lattice that smoothly transforms to valence circular rings in the
      ground-state configurations for both potentials.

PMID- 28505837
TI  - Electrophoresis of a polarizable charged colloid with hydrophobic surface: A
      numerical study.
AB  - We consider the electrophoresis of a charged colloid for a generalized situation
      in which the particle is considered to be polarizable and the surface exhibits
      hydrophobicity. The dielectric polarization of the particle creates a nonlinear
      dependence of the electrophoretic velocity on the applied electric field, and the
      core hydrophobicity amplifies the fluid convection in the Debye layer. Thus, a
      linear analysis is no longer applicable for this situation. The present analysis
      is based on the numerical solution of the nonlinear electrokinetic equations
      based on the Navier-Stokes-Nernst-Planck-Poisson equations coupled with the
      Laplace equation for the electric field within the dielectric particle. The
      hydrophobicity of the particle may influence its electric polarization by
      enhancing the convective transport of ions. The nonlinear effects, such as double
      layer polarization and relaxation, are also influenced by the hydrophobicity of
      the particle surface. The present results compare well for a lower range of the
      applied electric field and surface charge density with the existing results for a
      perfectly dielectric particle with a hydrophobic surface based on the first-order
      perturbation analysis due to Khair and Squires [Phys. Fluids 21, 042001
      (2009)PHFLE61070-663110.1063/1.3116664]. Dielectric polarization creates a
      reduction in particle electrophoretic velocity, and its impact is strong for a
      moderate range of Debye length. A quantitative measure of the nonlinear effects
      is demonstrated by comparing the electrophoretic velocity with an existing linear
      model.

PMID- 28505836
TI  - Stationary patterns in star networks of bistable units: Theory and application to
      chemical reactions.
AB  - We present theoretical and experimental studies on pattern formation with
      bistable dynamical units coupled in a star network configuration. By applying a
      localized perturbation to the central or the peripheral elements, we demonstrate
      the subsequent spreading, pinning, or retraction of the activations; such
      analysis enables the characterization of the formation of stationary patterns of
      localized activity. The results are interpreted with a theoretical analysis of a
      simplified bistable reaction-diffusion model. Weak coupling results in trivial
      pinned states where the activation cannot propagate. At strong coupling, a
      uniform state is expected with active or inactive elements at small or large
      degree networks, respectively. A nontrivial stationary spatial pattern,
      corresponding to an activation pinning, is predicted to occur at an intermediate
      number of peripheral elements and at intermediate coupling strengths, where the
      central activation of the network is pinned, but the peripheral activation
      propagates toward the center. The results are confirmed in experiments with star
      networks of bistable electrochemical reactions. The experiments confirm the
      existence of the stationary spatial patterns and the dependence of coupling
      strength on the number of peripheral elements for transitions between pinned and
      retreating or spreading fronts in forced network configurations (where the
      central or periphery elements are forced to maintain their states).

PMID- 28505838
TI  - Correlations induced by depressing synapses in critically self-organized networks
      with quenched dynamics.
AB  - In a recent work, mean-field analysis and computer simulations were employed to
      analyze critical self-organization in networks of excitable cellular automata
      where randomly chosen synapses in the network were depressed after each spike
      (the so-called annealed dynamics). Calculations agree with simulations of the
      annealed version, showing that the nominal branching ratio sigma converges to
      unity in the thermodynamic limit, as expected of a self-organized critical
      system. However, the question remains whether the same results apply to the
      biological case where only the synapses of firing neurons are depressed (the so
      called quenched dynamics). We show that simulations of the quenched model yield
      significant deviations from sigma=1 due to spatial correlations. However, the
      model is shown to be critical, as the largest eigenvalue of the synaptic matrix
      approaches unity in the thermodynamic limit, that is, lambda_{c}=1. We also study
      the finite size effects near the critical state as a function of the parameters
      of the synaptic dynamics.

PMID- 28505839
TI  - Explosive percolation on a scale-free multifractal weighted planar stochastic
      lattice.
AB  - In this article, we investigate explosive bond percolation (EBP) with the product
      rule, formally known as the Achlioptas process, on a scale-free multifractal
      weighted planar stochastic lattice. One of the key features of the EBP transition
      is the delay, compared to the corresponding random bond percolation (RBP), in the
      onset of the spanning cluster. However, when it happens, it happens so
      dramatically that initially it was believed, although ultimately proved wrong,
      that explosive percolation (EP) exhibits a first-order transition. In the case of
      EP, much effort has been devoted to resolving the issue of its order of
      transition and almost no effort has been devoted to finding the critical point,
      critical exponents, etc., to classify it into universality classes. This is in
      sharp contrast to the situation for classical random percolation. We do not even
      know all the exponents of EP for a regular planar lattice or for an Erdos-Renyi
      network. We first find the critical point p_{c} numerically and then obtain all
      the critical exponents, beta, gamma, and nu, as well as the Fisher exponent tau
      and the fractal dimension d_{f} of the spanning cluster. We also compare our
      results for EBP with those for RBP and find that all the exponents of EBP obey
      the same scaling relations as do those for RBP. Our findings suggest that EBP is
      not special except for the fact that the exponent beta is unusually small
      compared to that for RBP.

PMID- 28505840
TI  - Evolutionary fields can explain patterns of high-dimensional complexity in
      ecology.
AB  - One of the properties that make ecological systems so unique is the range of
      complex behavioral patterns that can be exhibited by even the simplest
      communities with only a few species. Much of this complexity is commonly
      attributed to stochastic factors that have very high-degrees of freedom. Orthodox
      study of the evolution of these simple networks has generally been limited in its
      ability to explain complexity, since it restricts evolutionary adaptation to an
      inertia-free process with few degrees of freedom in which only gradual,
      moderately complex behaviors are possible. We propose a model inspired by
      particle-mediated field phenomena in classical physics in combination with
      fundamental concepts in adaptation, which suggests that small but high
      dimensional chaotic dynamics near to the adaptive trait optimum could help
      explain complex properties shared by most ecological datasets, such as
      aperiodicity and pink, fractal noise spectra. By examining a simple predator-prey
      model and appealing to real ecological data, we show that this type of complexity
      could be easily confused for or confounded by stochasticity, especially when
      spurred on or amplified by stochastic factors that share variational and spectral
      properties with the underlying dynamics.

PMID- 28505841
TI  - Optimal strengthening of particle-loaded liquid foams.
AB  - Foams made of complex fluids such as particle suspensions have a great potential
      for the development of advanced aerated materials. In this paper, we study the
      rheological behavior of liquid foams loaded with granular suspensions. We focus
      on the effect of small particles, i.e., particle-to-bubble size ratio smaller
      than 0.1, and we measure the complex modulus as a function of particle size and
      particle volume fraction. With respect to previous work, the results highlight a
      new elastic regime characterized by unequaled modulus values as well as
      independence of size ratio. A careful investigation of the material
      microstructure reveals that particles organize through the network between the
      gas bubbles and form a granular skeleton structure with tightly packed particles.
      The latter is proven to be responsible for the reported new elastic regime.
      Rheological probing performed by strain sweep reveals a two-step yielding of the
      material: The first one occurs at small strain and is clearly attributed to
      yielding of the granular skeleton; the second one corresponds to the yielding of
      the bubble assembly, as observed for particle-free foams. Moreover, the elastic
      modulus measured at small strain is quantitatively described by models for solid
      foams in assuming that the granular skeleton possesses a bulk elastic modulus of
      order 100 kPa. Additional rheology experiments performed on the bulk granular
      material indicate that this surprisingly high value can be understood as soon as
      the magnitude of the confinement pressure exerted by foam bubbles on packed
      grains is considered.

PMID- 28505842
TI  - Spontaneous symmetry breaking due to the trade-off between attractive and
      repulsive couplings.
AB  - Spontaneous symmetry breaking is an important phenomenon observed in various
      fields including physics and biology. In this connection, we here show that the
      trade-off between attractive and repulsive couplings can induce spontaneous
      symmetry breaking in a homogeneous system of coupled oscillators. With a simple
      model of a system of two coupled Stuart-Landau oscillators, we demonstrate how
      the tendency of attractive coupling in inducing in-phase synchronized (IPS)
      oscillations and the tendency of repulsive coupling in inducing out-of-phase
      synchronized oscillations compete with each other and give rise to symmetry
      breaking oscillatory states and interesting multistabilities. Further, we provide
      explicit expressions for synchronized and antisynchronized oscillatory states as
      well as the so called oscillation death (OD) state and study their stability. If
      the Hopf bifurcation parameter (lambda) is greater than the natural frequency
      (omega) of the system, the attractive coupling favors the emergence of an
      antisymmetric OD state via a Hopf bifurcation whereas the repulsive coupling
      favors the emergence of a similar state through a saddle-node bifurcation. We
      show that an increase in the repulsive coupling not only destabilizes the IPS
      state but also facilitates the reentrance of the IPS state.

PMID- 28505843
TI  - Quantum resonant activation.
AB  - Quantum resonant activation is investigated for the archetype setup of an
      externally driven two-state (spin-boson) system subjected to strong dissipation
      by means of both analytical and extensive numerical calculations. The phenomenon
      of resonant activation emerges in the presence of either randomly fluctuating or
      deterministic periodically varying driving fields. Addressing the incoherent
      regime, a characteristic minimum emerges in the mean first passage time to reach
      an absorbing neighboring state whenever the intrinsic time scale of the
      modulation matches the characteristic time scale of the system dynamics. For the
      case of deterministic periodic driving, the first passage time probability
      density function (pdf) displays a complex, multipeaked behavior, which depends
      crucially on the details of initial phase, frequency, and strength of the
      driving. As an interesting feature we find that the mean first passage time
      enters the resonant activation regime at a critical frequency nu^{*} which
      depends very weakly on the strength of the driving. Moreover, we provide the
      relation between the first passage time pdf and the statistics of residence
      times.

PMID- 28505844
TI  - Equation of state, phonons, and lattice stability of ultrafast warm dense matter.
AB  - Using the two-temperature model for ultrafast matter (UFM), we compare the
      equation of state, pair-distribution functions g(r), and phonons using the
      neutral pseudoatom (NPA) model with results from density functional theory (DFT)
      codes and molecular dynamics (MD) simulations for Al, Li, and Na. The NPA
      approach uses state-dependent first-principles pseudopotentials from an "all
      electron" DFT calculation with finite-T exchange-correlation functional (XCF). It
      provides pair potentials, structure factors, the "bound" and "free" states, as
      well as a mean ionization Z[over -] unambiguously. These are not easily
      accessible via DFT+MD calculations which become prohibitive for T/T_{F} exceeding
      ~0.6, where T_{F} is the Fermi temperature. Hence, both DFT+MD and NPA methods
      can be compared up to ~8eV, while higher T can be addressed via the NPA. The high
      T_{e} phonon calculations raise the question of UFM lattice stability and surface
      ablation in thin UFM samples. The ablation forces in a UFM slab are used to
      define an "ablation time" competing with phonon formation times in thin UFM
      samples. Excellent agreement for all properties is found between NPA and standard
      DFT codes, even for Li where a strongly nonlocal pseudopotential is used in DFT
      codes. The need to use pseudopotentials appropriate to the ionization state
      Z[over -] is emphasized. The effect of finite-T XCF is illustrated via its effect
      on the pressure and the electron-density distribution at a nucleus.

PMID- 28505845
TI  - Thermodynamics of complexity and pattern manipulation.
AB  - Many organisms capitalize on their ability to predict the environment to maximize
      available free energy and reinvest this energy to create new complex structures.
      This functionality relies on the manipulation of patterns-temporally ordered
      sequences of data. Here, we propose a framework to describe pattern manipulators
      devices that convert thermodynamic work to patterns or vice versa-and use them to
      build a "pattern engine" that facilitates a thermodynamic cycle of pattern
      creation and consumption. We show that the least heat dissipation is achieved by
      the provably simplest devices, the ones that exhibit desired operational behavior
      while maintaining the least internal memory. We derive the ultimate limits of
      this heat dissipation and show that it is generally nonzero and connected with
      the pattern's intrinsic crypticity-a complexity theoretic quantity that captures
      the puzzling difference between the amount of information the pattern's past
      behavior reveals about its future and the amount one needs to communicate about
      this past to optimally predict the future.

PMID- 28505846
TI  - Traveling waves and worms in ac-driven electroconvection under external
      multiplicative noise.
AB  - In the presence of external multiplicative noise, ac-driven electroconvection
      (EC) in a nematic liquid crystal is investigated. Noise-induced traveling waves
      (TWs) including localized ones (worms) are found with a typical, stationary wave.
      Three kinds of TWs are classified by their dynamic features (e.g., noise
      intensity-dependent Hopf frequency and space-time map). Moreover, ac frequency
      dependent threshold voltages of EC are examined in high noise intensities causing
      abnormal charge redistribution of the EC cell, and the roles of ac and noise
      fields with respect to TWs are elucidated in successive pattern evolutions. The
      mechanism of TWs is discussed in terms of a locally perturbed dynamic
      conductivity due to the noise field additionally applied to the EC; such a
      conductivity can be related to a weak-electrolyte model for a Hopf bifurcation to
      a TW.

PMID- 28505847
TI  - Numerical analysis of the lattice Boltzmann method for simulation of linear
      acoustic waves.
AB  - We analyze a linear lattice Boltzmann (LB) formulation for simulation of linear
      acoustic wave propagation in heterogeneous media. We employ the single-relaxation
      time Bhatnagar-Gross-Krook as well as the general multirelaxation-time collision
      operators. By calculating the dispersion relation for various 2D lattices, we
      show that the D2Q5 lattice is the most suitable model for the linear acoustic
      problem. We also implement a grid-refinement algorithm for the LB scheme to
      simulate waves propagating in a heterogeneous medium with velocity contrasts. Our
      results show that the LB scheme performance is comparable to the classical second
      order finite-difference schemes. Given its efficiency for parallel computation,
      the LB method can be a cost effective tool for the simulation of linear acoustic
      waves in complex geometries and multiphase media.

PMID- 28505848
TI  - Emergent community agglomeration from data set geometry.
AB  - In the statistical learning language, samples are snapshots of random vectors
      drawn from some unknown distribution. Such vectors usually reside in a high
      dimensional Euclidean space, and thus the "curse of dimensionality" often
      undermines the power of learning methods, including community detection and
      clustering algorithms, that rely on Euclidean geometry. This paper presents the
      idea of effective dissimilarity transformation (EDT) on empirical dissimilarity
      hyperspheres and studies its effects using synthetic and gene expression data
      sets. Iterating the EDT turns a static data distribution into a dynamical process
      purely driven by the empirical data set geometry and adaptively ameliorates the
      curse of dimensionality, partly through changing the topology of a Euclidean
      feature space R^{n} into a compact hypersphere S^{n}. The EDT often improves the
      performance of hierarchical clustering via the automatic grouping information
      emerging from global interactions of data points. The EDT is not restricted to
      hierarchical clustering, and other learning methods based on pairwise
      dissimilarity should also benefit from the many desirable properties of EDT.

PMID- 28505849
TI  - Compaction of noncohesive and cohesive granular materials under vibrations:
      Experiments and stochastic model.
AB  - We study the time evolution of the compaction of a noncohesive or cohesive
      granular material submitted to shaking through experiments and a stochastic
      model. Beyond well-known empirical expressions, we show that the characteristic
      time scales depend on the number of objects in the assembly. For a noncohesive
      granular material, the compaction time scale is governed by the number of
      individual grains in the system. In the case of a cohesive granular material, a
      two-scale model (individual particles and clusters) allows one to mimic the time
      evolution of the compaction of an actual cohesive powder driven by horizontal
      vibrations. In this case, the two time scales are associated with the numbers of
      clusters and grains, respectively.

PMID- 28505850
TI  - Damage cluster distributions in numerical concrete at the mesoscale.
AB  - We investigate the size distribution of damage clusters in concrete under
      uniaxial tension loading conditions. Using the finite-element method, the
      concrete is modeled at the mesoscale by a random distribution of elastic
      spherical aggregates within an elastic mortar paste. The propagation and
      coalescence of damage zones are then simulated by means of dynamically inserted
      cohesive elements. Dynamic failure analysis shows that the size distribution of
      damage clusters follows a power law when a system-spanning cluster is first
      observed, with an exponent close to that of percolation theory. This is found for
      a range of selected mesostructural parameters, material defects, and applied
      strain rates. In all cases, the system-spanning cluster occurs prior to the onset
      of local decohesion, a regime of crack nucleation and propagation, and eventual
      material failure. The resulting fully damaged crack surfaces after failure are
      found to be only weakly correlated with the percolated damage region structures.

PMID- 28505851
TI  - Rogue waves in nonlocal media.
AB  - The generation of rogue waves is investigated in a class of nonlocal nonlinear
      Schrodinger (NLS) equations. In this system, modulation instability is suppressed
      as the effect of nonlocality increases. Despite this fact, there is a parameter
      regime where the number and amplitude of the rogue events increase as compared to
      the standard NLS equation, which is a limit of the system when nonlocality
      vanishes. Furthermore, the nature of these waves is investigated; while no
      analytical solutions are known to model these events, it is shown, numerically,
      that these rogue events differ significantly from the rational soliton
      (Peregrine) solution of the limiting NLS equation. The universal structure of the
      associated rogue waves is discussed and a local description is presented. These
      results can help in the experimental realization of rogue waves in these media.

PMID- 28505852
TI  - Generation of higher-order rogue waves from multibreathers by double degeneracy
      in an optical fiber.
AB  - In this paper, we construct a special kind of breather solution of the nonlinear
      Schrodinger (NLS) equation, the so-called breather-positon (b-positon for short),
      which can be obtained by taking the limit lambda_{j}->lambda_{1} of the Lax pair
      eigenvalues in the order-n periodic solution, which is generated by the n-fold
      Darboux transformation from a special "seed" solution-plane wave. Further, an
      order-n b-positon gives an order-n rogue wave under a limit lambda_{1}
      >lambda_{0}. Here, lambda_{0} is a special eigenvalue in a breather of the NLS
      equation such that its period goes to infinity. Several analytical plots of order
      2 breather confirm visually this double degeneration. The last limit in this
      double degeneration can be realized approximately in an optical fiber governed by
      the NLS equation, in which an injected initial ideal pulse is created by a
      frequency comb system and a programable optical filter (wave shaper) according to
      the profile of an analytical form of the b-positon at a certain position z_{0}.
      We also suggest a new way to observe higher-order rogue waves generation in an
      optical fiber, namely, measure the patterns at the central region of the higher
      order b-positon generated by above ideal initial pulses when lambda_{1} is very
      close to the lambda_{0}. The excellent agreement between the numerical solutions
      generated from initial ideal inputs with a low signal-to-noise ratio and
      analytical solutions of order-2 b-positon supports strongly this way in a
      realistic optical fiber system. Our results also show the validity of the
      generating mechanism of a higher-order rogue waves from a multibreathers through
      the double degeneration.

PMID- 28505853
TI  - Dynamic stabilization of Janus sphere trans-dimers.
AB  - We experimentally investigated the self-assembly of chemically active colloidal
      Janus spheres into dimers. The trans-dimer conformation, in which the two active
      sites are oriented roughly in opposite directions and the particles are osculated
      at their equators, becomes dominant as the hydrogen peroxide fuel concentration
      increases. Our observations suggest high spinning frequency combined with little
      translational motion is at least partially responsible for the stabilization of
      the trans-dimer as activity increases.

PMID- 28505854
TI  - Mean-field equations for neuronal networks with arbitrary degree distributions.
AB  - The emergent dynamics in networks of recurrently coupled spiking neurons depends
      on the interplay between single-cell dynamics and network topology. Most
      theoretical studies on network dynamics have assumed simple topologies, such as
      connections that are made randomly and independently with a fixed probability
      (Erdos-Renyi network) (ER) or all-to-all connected networks. However, recent
      findings from slice experiments suggest that the actual patterns of connectivity
      between cortical neurons are more structured than in the ER random network. Here
      we explore how introducing additional higher-order statistical structure into the
      connectivity can affect the dynamics in neuronal networks. Specifically, we
      consider networks in which the number of presynaptic and postsynaptic contacts
      for each neuron, the degrees, are drawn from a joint degree distribution. We
      derive mean-field equations for a single population of homogeneous neurons and
      for a network of excitatory and inhibitory neurons, where the neurons can have
      arbitrary degree distributions. Through analysis of the mean-field equations and
      simulation of networks of integrate-and-fire neurons, we show that such networks
      have potentially much richer dynamics than an equivalent ER network. Finally, we
      relate the degree distributions to so-called cortical motifs.

PMID- 28505855
TI  - Theoretical models for magneto-sensitive elastomers: A comparison between
      continuum and dipole approaches.
AB  - In the literature, different theoretical models have been proposed to describe
      the properties of systems which consist of magnetizable particles that are
      embedded into an elastomer matrix. It is well known that such magneto-sensitive
      elastomers display a strong magneto-mechanical coupling when subjected to an
      external magnetic field. Nevertheless, the predictions of available models often
      vary significantly since they are based on different assumptions and
      approximations. Up to now the actual accuracy and the limits of applicability are
      widely unknown. In the present work, we compare the results of a microscale
      continuum and a dipolar mean field approach with regard to their predictions for
      the magnetostrictive response of magneto-sensitive elastomers and reveal some
      fundamental relations between the relevant quantities in both theories. It turns
      out that there is a very good agreement between both modeling strategies,
      especially for entirely random microstructures. In contrast, a comparison of the
      finite-element results with a modified approach, which-similar to the continuum
      model-is based on calculations with discrete particle distributions, reveals
      clear deviations. Our systematic analysis of the differences shows to what extent
      the dipolar mean field approach is superior to other dipole models.

PMID- 28505856
TI  - Information thermodynamics for feedback processes with the appearance of
      overshooting.
AB  - We investigate feedback processes with measurement-induced protocols for
      particular tasks that drive systems in specified directions in state spaces. We
      focus on mutual information as a measure of correlation between system and
      memory, which has been known to play a crucial role for the second law of
      information thermodynamics. The performance of task is enhanced in the early
      stage of driving, along with the decrease of correlation and mutual information
      due to the passage from initial measurement. However, we find that the
      performance is suppressed if the time of driving exceeds a threshold, which we
      call feedback overshooting. We find that a type of correlation, anticorrelation,
      between system and memory is built up as a result of overshooting and gives rise
      to regaining mutual information. We examine the effect of overshooting in detail
      from two examples. We study the Szilard engine for the task of work extraction.
      We also study a recurrent feedback with finite time interval for the task to
      reduce the mean square distance of a colloid below the value by thermal
      fluctuation. We find that recurrent feedback is stable only for a moderate range
      of time intervals and the intensity of feedback protocol. We discuss the problem
      of divergence of mutual information for error-free measurement.

PMID- 28505857
TI  - Ising spin glasses in two dimensions: Universality and nonuniversality.
AB  - Following numerous earlier studies, extensive simulations and analyses were made
      on the continuous interaction distribution Gaussian model and the discrete
      bimodal interaction distribution Ising spin glass (ISG) models in two dimensions
      [Lundow and Campbell, Phys. Rev. E 93, 022119 (2016)1539
      375510.1103/PhysRevE.93.022119]. Here we further analyze the bimodal and Gaussian
      data together with data on two other continuous interaction distribution two
      dimensional ISG models, the uniform and the Laplacian models, and three other
      discrete interaction distribution models, a diluted bimodal model, an
      "antidiluted" model, and a more exotic symmetric Poisson model. Comparisons
      between the three continuous distribution models show that not only do they share
      the same exponent eta=0 but that to within the present numerical precision they
      share the same critical exponent nu also, and so lie in a single universality
      class. On the other hand the critical exponents of the four discrete distribution
      models are not the same as those of the continuous distributions, and the present
      data strongly indicate that they differ from one discrete distribution model to
      another. This is evidence that discrete distribution ISG models in two dimensions
      have nonzero values of the critical exponent eta and do not lie in a single
      universality class.

PMID- 28505858
TI  - Tricritical behavior of nonequilibrium Ising spins in fluctuating environments.
AB  - We investigate the phase transitions in a coupled system of Ising spins and a
      fluctuating network. Each spin interacts with q neighbors through links of the
      rewiring network. The Ising spins and the network are in thermal contact with the
      heat baths at temperatures T_{S} and T_{L}, respectively, so the whole system is
      driven out of equilibrium for T_{S}?T_{L}. The model is a generalization of the q
      neighbor Ising model [A. Jedrzejewski et al., Phys. Rev. E 92, 052105
      (2015)PLEEE81539-375510.1103/PhysRevE.92.052105], which corresponds to the
      limiting case of T_{L}=infinity. Despite the mean-field nature of the
      interaction, the q-neighbor Ising model was shown to display a discontinuous
      phase transition for q>=4. Setting up the rate equations for the magnetization
      and the energy density, we obtain the phase diagram in the T_{S}-T_{L} parameter
      space. The phase diagram consists of a ferromagnetic phase and a paramagnetic
      phase. The two phases are separated by a continuous phase transition belonging to
      the mean-field universality class or by a discontinuous phase transition with an
      intervening coexistence phase. The equilibrium system with T_{S}=T_{L} falls into
      the former case while the q-neighbor Ising model falls into the latter case. At
      the tricritical point, the system exhibits the mean-field tricritical behavior.
      Our model demonstrates a possibility that a continuous phase transition turns
      into a discontinuous transition by a nonequilibrium driving. Heat flow induced by
      the temperature difference between two heat baths is also studied.

PMID- 28505859
TI  - Interpolation between low and high temperatures of the specific heat for spin
      systems.
AB  - The high temperature expansion (HTE) of the specific heat of a spin system fails
      at low temperatures, even if it is combined with a Pade approximation. On the
      other hand, we often have information about the low-temperature asymptotics (LTA)
      of the system. Interpolation methods combine both kind of information, HTE and
      LTA, in order to obtain an approximation of the specific heat that holds for the
      whole temperature range. Here we revisit the entropy method that has been
      previously published and propose two variants that better cope with problems of
      the entropy method for gapped systems. We compare all three methods applied to
      the antiferromagnetic Haldane spin-one chain and especially apply the second
      variant, called log Z method, to the cuboctahedron for different spin quantum
      numbers. In particular, we demonstrate that the interpolation method is able to
      detect an extra low-temperature maximum in the specific heat that may appear if a
      separation of two energy scales is present in the considered system. Finally, we
      illustrate how interpolation also works for classical spin systems.

PMID- 28505860
TI  - Nonmonotonic DNA-length-dependent mobility in pluronic gels.
AB  - Two-dimensional electrophoresis was used to analyze the mobility of DNA fragments
      in micellar gels of pluronic F127 (EO_{100}PO_{70}EO_{100}) and pluronic P123
      (EO_{20}PO_{70}EO_{20}). The 20-3500 base pair DNA fragments were separated by
      size first in agarose gels, and then in pluronic gels at room temperature. In
      agarose gels, the DNA mobility decreases monotonically with increasing DNA
      length. In pluronic gels, however, the mobility varies nonmonotonically according
      to fragment lengths that are strongly correlated with the diameter of the
      spherical micelles. Brownian dynamics (BD) simulations with short-ranged intra
      DNA hydrodynamic interactions were performed to numerically calculate the length
      dependent mobility in pluronic lattices. The rising and falling trends, as well
      as the oscillations of mobility, were captured by the coarse-grained BD
      simulations. Molecular dynamics simulations in pluronic F127, with explicitly
      modeled micelle coronas, justified that the hydrodynamic interactions mediated by
      the complex fluid of hydrated poly(ethylene oxide) are a possible reason for the
      initial rise of mobility with DNA length.

PMID- 28505861
TI  - Landau-Zener tunneling of solitons.
AB  - We consider Landau-Zener tunneling of solitons in a weakly coupled two-channel
      system, for this purpose we construct a simple mechanical system using two weakly
      coupled chains of nonlinear oscillators with gradually decreasing (first chain)
      and increasing (second chain) masses. The model allows us to consider soliton
      propagation and Landau-Zener tunneling between the chains. It is shown that
      soliton tunneling characteristics become drastically dependent on its amplitude
      in nonlinear regime. The validity of the developed tunneling theory is justified
      via comparison with direct numerical simulations on oscillator ladder system.

PMID- 28505862
TI  - Thermodynamic state variables in quasiequilibrium ultracold neutral plasma.
AB  - The pressure and internal energy of an ultracold plasma in a state of
      quasiequilibrium are evaluated using classical molecular dynamics simulations.
      Coulomb collapse is avoided by modeling electron-ion interactions using an
      attractive Coulomb potential with a repulsive core. We present a method to
      separate the contribution of classical bound states, which form due to
      recombination, from the contribution of free charges when evaluating these
      thermodynamic state variables. It is found that the contribution from free
      charges is independent of the choice of repulsive core length scale when it is
      sufficiently short-ranged. The partial pressure associated with the free charges
      is found to closely follow that of the one-component plasma model, reaching
      negative values at strong coupling, while the total system pressure remains
      positive. This pseudopotential model is also applied to Debye-Huckel theory to
      describe the weakly coupled regime.

PMID- 28505863
TI  - Mixing and the fractal geometry of piecewise isometries.
AB  - Mathematical concepts often have applicability in areas that may have surprised
      their original developers. This is the case with piecewise isometries (PWIs),
      which transform an object by cutting it into pieces that are then rearranged to
      reconstruct the original object, and which also provide a paradigm to study
      mixing via cutting and shuffling in physical sciences and engineering. Every PWI
      is characterized by a geometric structure called the exceptional set, E, whose
      complement comprises nonmixing regions in the domain. Varying the parameters that
      define the PWI changes both the structure of E as well as the degree of mixing
      the PWI produces, which begs the question of how to determine which parameters
      produce the best mixing. Motivated by mixing of yield stress materials, for
      example granular media, in physical systems, we use numerical simulations of PWIs
      on a hemispherical shell and examine how the fat fractal properties of E relate
      to the degree of mixing for any particular PWI. We present numerical evidence
      that the fractional coverage of E negatively correlates with the intensity of
      segregation, a standard measure for the degree of mixing, which suggests that
      fundamental properties of E such as fractional coverage can be used to predict
      the effectiveness of a particular PWI as a mixing mechanism.

PMID- 28505864
TI  - Optimal subgrid scheme for shell models of turbulence.
AB  - We discuss a theoretical framework to define an optimal subgrid closure for shell
      models of turbulence. The closure is based on the ansatz that consecutive shell
      multipliers are short-range correlated, following the third hypothesis of
      Kolmogorov formulated for similar quantities for the original three-dimensional
      Navier-Stokes turbulence. We also propose a series of systematic approximations
      to the optimal model by assuming different degrees of correlations across scales
      among amplitudes and phases of consecutive multipliers. We show numerically that
      such low-order closures work well, reproducing all known properties of the large
      scale dynamics including anomalous scaling. We found small but systematic
      discrepancies only for a range of scales close to the subgrid threshold, which do
      not tend to disappear by increasing the order of the approximation. We speculate
      that the lack of convergence might be due to a structural instability, at least
      for the evolution of very fast degrees of freedom at small scales. Connections
      with similar problems for large eddy simulations of the three-dimensional Navier
      Stokes equations are also discussed.

PMID- 28505865
TI  - Critical behavior of the two-dimensional nonequilibrium zero-temperature random
      field Ising model on a triangular lattice.
AB  - We present a numerical study of the critical behavior of the nonequilibrium zero
      temperature random field Ising model in two dimensions on a triangular lattice.
      Our findings, based on the scaling analysis and collapse of data collected in
      extensive simulations of systems with linear sizes up to L=65536, show that the
      model is in a different universality class than the same model on a quadratic
      lattice, which is relevant for a better understanding of model universality and
      the analysis of experimental data.

PMID- 28505866
TI  - Spatial uniformity in the power-grid system.
AB  - Robust synchronization is indispensable for stable operation of a power grid.
      Recently, it has been reported that a large number of decentralized generators,
      rather than a small number of large power plants, provide enhanced
      synchronization together with greater robustness against structural failures. In
      this paper, we systematically control the spatial uniformity of the geographical
      distribution of generators and conclude that the more uniformly generators are
      distributed, the more enhanced synchronization occurs. In the presence of
      temporal failures of power sources, we observe that spatial uniformity helps the
      power grid to recover stationarity in a shorter time. We also discuss practical
      implications of our results in designing the structure of a power-grid network.

PMID- 28505867
TI  - Collective dynamics out of thermodynamic equilibrium.
AB  - Thorough numerical studies reveal that spatially extended dissipative systems
      with long-range interactions may give rise to a large-scale dynamics. This
      phenomenon, which generalizes mean-field chaos, can be interpreted as a form of
      subtle pattern formation, where a chaotic microscopic dynamics coexists with a
      macroscopic irregular behavior, sustained by the spontaneous emergence of long
      wavelength "hydrodynamic" modes. This regime can emerge only if the coupling is
      sufficiently long ranged, otherwise normal space-time chaos is observed. In
      Stuart-Landau oscillators a further regime is found, where the amplitude of the
      hydrodynamic modes exhibits an anomalous intermediate scaling between that of
      collective and standard space-time chaos.

PMID- 28505868
TI  - Limiting similarity of competitive species and demographic stochasticity.
AB  - The limiting similarity of competitive species and its relationship with the
      competitive exclusion principle is still one of the most important concepts in
      ecology. In the 1970s, May [R. M. May, Stability and Complexity in Model
      Ecosystems (Princeton University, Princeton, NJ, 1973)] developed a concise
      theoretical framework to investigate the limiting similarity of competitive
      species. His theoretical results show that no limiting similarity threshold of
      competitive species can be identified in the deterministic model system whereby
      species more similar than this threshold never coexist. Theoretically, for
      competitive species coexisting in an unvarying environment, deterministic
      interspecific interactions and demographic stochasticity can be considered two
      sides of a coin. To investigate how the "tension" between these two forces
      affects the coexistence of competing species, a simple two-species competitive
      system based only on May's model system is transformed into an equivalent
      replicator equation. The effect of demographic stochasticity on the system
      stability is measured by the expected drift of the Lyapunov function. Our main
      results show that the limiting similarity of competitive species should not be
      considered to be an absolute measure. Specifically, very similar competitive
      species should be able to coexist in an environment with a high productivity
      level but big differences between competitive species should be necessary in an
      ecosystem with a low productivity level.

PMID- 28505869
TI  - Instability onset and scaling laws of an auto-oscillating turbulent flow in a
      complex plasma.
AB  - We study a complex plasma under microgravity conditions that is first stabilized
      with an oscillating electric field. Once the stabilization is stopped, the so
      called heartbeat instability develops. We study how the kinetic energy spectrum
      changes during and after the onset of the instability and compare with the double
      cascade predicted by Kraichnan and Leith for two-dimensional turbulence. The
      onset of the instability manifests clearly in the ratio of the reduced rates of
      cascade of energy and enstrophy and in the power-law exponents of the energy
      spectra.

PMID- 28505871
TI  - Phase behavior of the thermotropic melt of asymmetric V-shaped molecules.
AB  - The phase behavior of the monodisperse melt of V-shaped molecules composed of two
      rigid segments of different lengths joined at their ends at an external angle
      alpha has been examined within the Landau-de Gennes approach. Each rigid segment
      consists of a sequence of monomer units; the anisotropic interactions in the
      system are assumed to be of the Maier-Saupe form. The coefficients of the Landau
      de Gennes free-energy expansion have been found from a microscopic model of V
      shaped molecule. A single Landau point at which the system undergoes direct
      continuous transition from isotropic to biaxial nematic phase is found for
      asymmetry parameter phi=1/3 or phi=2/3, where phi is the number fraction of
      monomer units in one of the segments. Two Landau points are found in a range
      1/3<phi<2/3. Only isotropic and nematic states are found to be stable for
      0<=phi<1/3 and 2/3<phi<=1. Regions of stability of isotropic, prolate uniaxial,
      and biaxial nematic phases are found for phi=1/3 and phi=2/3. In addition, a
      stable oblate uniaxial phase is revealed if asymmetry parameter falls in the
      range 1/3<phi<2/3. The region of stability of the biaxial nematic phase becomes
      smaller as parameter phi increases from 1/3 to 1/2 (or decreases from 2/3 to
      1/2). Coefficients of the gradient terms have been found; for certain values of
      asymmetry parameter these coefficients can become negative in some ranges of
      angles.

PMID- 28505870
TI  - First-order phase transition in a majority-vote model with inertia.
AB  - We generalize the original majority-vote model by incorporating inertia into the
      microscopic dynamics of the spin flipping, where the spin-flip probability of any
      individual depends not only on the states of its neighbors, but also on its own
      state. Surprisingly, the order-disorder phase transition is changed from a usual
      continuous or second-order type to a discontinuous or first-order one when the
      inertia is above an appropriate level. A central feature of such an explosive
      transition is a strong hysteresis behavior as noise intensity goes forward and
      backward. Within the hysteresis region, a disordered phase and two symmetric
      ordered phases are coexisting and transition rates between these phases are
      numerically calculated by a rare-event sampling method. A mean-field theory is
      developed to analytically reveal the property of this phase transition.

PMID- 28505872
TI  - Quantum corrections of the truncated Wigner approximation applied to an exciton
      transport model.
AB  - We modify the path integral representation of exciton transport in open quantum
      systems such that an exact description of the quantum fluctuations around the
      classical evolution of the system is possible. As a consequence, the time
      evolution of the system observables is obtained by calculating the average of a
      stochastic difference equation which is weighted with a product of
      pseudoprobability density functions. From the exact equation of motion one can
      clearly identify the terms that are also present if we apply the truncated Wigner
      approximation. This description of the problem is used as a basis for the
      derivation of a new approximation, whose validity goes beyond the truncated
      Wigner approximation. To demonstrate this we apply the formalism to a donor
      acceptor transport model.

PMID- 28505873
TI  - Restoration of dimensional reduction in the random-field Ising model at five
      dimensions.
AB  - The random-field Ising model is one of the few disordered systems where the
      perturbative renormalization group can be carried out to all orders of
      perturbation theory. This analysis predicts dimensional reduction, i.e., that the
      critical properties of the random-field Ising model in D dimensions are identical
      to those of the pure Ising ferromagnet in D-2 dimensions. It is well known that
      dimensional reduction is not true in three dimensions, thus invalidating the
      perturbative renormalization group prediction. Here, we report high-precision
      numerical simulations of the 5D random-field Ising model at zero temperature. We
      illustrate universality by comparing different probability distributions for the
      random fields. We compute all the relevant critical exponents (including the
      critical slowing down exponent for the ground-state finding algorithm), as well
      as several other renormalization-group invariants. The estimated values of the
      critical exponents of the 5D random-field Ising model are statistically
      compatible to those of the pure 3D Ising ferromagnet. These results support the
      restoration of dimensional reduction at D=5. We thus conclude that the failure of
      the perturbative renormalization group is a low-dimensional phenomenon. We close
      our contribution by comparing universal quantities for the random-field problem
      at dimensions 3<=D<6 to their values in the pure Ising model at D-2 dimensions,
      and we provide a clear verification of the Rushbrooke equality at all studied
      dimensions.

PMID- 28505874
TI  - General neck condition for the limit shape of budding vesicles.
AB  - The shape equation and linking conditions for a vesicle with two phase domains
      are derived. We refine the conjecture on the general neck condition for the limit
      shape of a budding vesicle proposed by Julicher and Lipowsky [Phys. Rev. Lett.
      70, 2964 (1993)PRLTAO0031-900710.1103/PhysRevLett.70.2964; Phys. Rev. E 53, 2670
      (1996)1063-651X10.1103/PhysRevE.53.2670], and then we use the shape equation and
      linking conditions to prove that this conjecture holds not only for axisymmetric
      budding vesicles, but also for asymmetric ones. Our study reveals that the mean
      curvature at any point on the membrane segments adjacent to the neck satisfies
      the general neck condition for the limit shape of a budding vesicle when the
      length scale of the membrane segments is much larger than the characteristic size
      of the neck but still much smaller than the characteristic size of the vesicle.

PMID- 28505875
TI  - Spatiotemporal canards in neural field equations.
AB  - Canards are special solutions to ordinary differential equations that follow
      invariant repelling slow manifolds for long time intervals. In realistic
      biophysical single-cell models, canards are responsible for several complex
      neural rhythms observed experimentally, but their existence and role in spatially
      extended systems is largely unexplored. We identify and describe a type of
      coherent structure in which a spatial pattern displays temporal canard behavior.
      Using interfacial dynamics and geometric singular perturbation theory, we
      classify spatiotemporal canards and give conditions for the existence of folded
      saddle and folded-node canards. We find that spatiotemporal canards are robust to
      changes in the synaptic connectivity and firing rate. The theory correctly
      predicts the existence of spatiotemporal canards with octahedral symmetry in a
      neural field model posed on the unit sphere.

PMID- 28505876
TI  - Intermittency-induced criticality in a resistor-inductor-diode circuit.
AB  - The current fluctuations of a driven resistor-inductor-diode circuit are
      investigated here looking for signatures of critical behavior monitored by the
      driving frequency. The experimentally obtained time series of the voltage drop
      across the resistor (as directly proportional to the current flowing through the
      circuit) were analyzed by means of the method of critical fluctuations in analogy
      to thermal critical systems. Intermittent criticality was revealed for a critical
      frequency band signifying the transition between the normal rectifier phase in
      the low frequencies and a full-wave conducting, capacitorlike phase in the high
      frequencies. The transition possesses critical characteristics with a
      characteristic exponent p_{l}=1.65. A fractal analysis in terms of the rescale
      range (R/RSS) and detrended fluctuation analysis methods yielded results fully
      compatible with the critical dynamics analysis. Suggestions for the
      interpretation of the observed behavior in terms of p-n junction operation are
      discussed.

PMID- 28505877
TI  - Destruction of Anderson localization in quantum nonlinear Schrodinger lattices.
AB  - The four-wave interaction in quantum nonlinear Schrodinger lattices with disorder
      is shown to destroy the Anderson localization of waves, giving rise to unlimited
      spreading of the nonlinear field to large distances. Moreover, the process is not
      thresholded in the quantum domain, contrary to its "classical" counterpart, and
      leads to an accelerated spreading of the subdiffusive type, with the dispersion
      <(Deltan)^{2}>~t^{1/2} for t->+infinity. The results, presented here, shed light
      on the origin of subdiffusion in systems with a broad distribution of relaxation
      times.

PMID- 28505879
TI  - Nitrogen utilization and environmental losses in organic greenhouse lettuce
      amended with two distinct biochars.
AB  - The potential of biochar to prevent nitrogen (N) losses and improve plant
      performance were studied across various levels of N input for two growing seasons
      in mesocosms simulating an organic lettuce production system. A silt loam soil
      was amended with pine chip (PC) and walnut shell (WS) biochar (10tha-1) in
      combination with five organic N fertilization rates (0, 56, 112, 168, and
      225kgNha-1). The N output through harvest, leachate, and N2O emissions were
      measured to assess N utilization and environmental losses of biochar-amended
      soils. For both biochars, only at the 100% N fertilization rate was lettuce
      biomass production improved with significant increases in N use efficiency (NUE);
      however, only PC biochar decreased N losses via leaching (at 100% N fertilization
      rate) and seasonal N2O emissions (at 50% N fertilization rate). Thus, due to
      increases in plant biomass and decreases in N losses, PC biochar significantly
      decreased the ratio of N lost over N exported in biomass. Findings from this
      study suggest that both WS and PC biochars can improve organic lettuce production
      but only at 225kgNha-1. Decreases in N losses via leachate and N2O emissions vary
      with fertilization level and biochar type.

PMID- 28505878
TI  - Suspended solid concentration reduces feeding in freshwater mussels.
AB  - We examined the effect of TSS concentration on the clearance rates (CR) of newly
      transformed juvenile and adult Lampsilis fasciola, L. siliquoidea, Ligumia
      nasuta, and Villosa iris, as increased total suspended solids (TSS) are thought
      to interfere with feeding processes. Mussel CR were measured in aerated (or
      swirled for juveniles) chambers at TSS concentrations up to 15mgL-1 for
      laboratory-transformed juveniles, and up to 100mgL-1 for adult mussels. The CR of
      one-week old animals increased with TSS concentration, likely due to ontological
      differences in feeding (pedal vs. suspension feeding) and gill development, but
      CR decreased monotonically with TSS concentration in older animals (two-, three-
      and four-week old juveniles). The CR of adult mussels were significantly lower at
      TSS concentrations >=8mgL-1, which represented a threshold in CR. Although this
      threshold occurred at similar concentrations across the four species, the decline
      in CR was largest in L. fasciola (46% compared to no-TSS control), and smallest
      in V. iris (21%). Differences among species are likely related to differences in
      the TSS and substrate found in their source rivers given that greater decline
      occurred for species in rivers with relatively lower TSS. The decrease in CR as
      TSS increased is consistent across marine and freshwater bivalves, at both
      juvenile and adult stages. The decrease in feeding was five times greater in
      juvenile compared to adult bivalves, which indicates how the vulnerability to
      environmental stressors differ across life stages. These results demonstrate that
      TSS reduces suspension feeding rates in freshwater unionids, therefore TSS should
      be managed to ensure their survival.

PMID- 28505881
TI  - Herbaceous or Salix miyabeana 'SX64' narrow buffer strips as a means to minimize
      glyphosate and aminomethylphosphonic acid leaching from row crop fields.
AB  - Glyphosate is the most widely used herbicide worldwide and is now frequently
      detected in surface waters of agricultural regions, notably in Quebec (Canada).
      Numerous legislations require vegetated riparian buffer strips (RBS) along
      agricultural streams. Quebec policy requires 3-meter-wide RBS. The present study
      evaluates the efficiency of narrow herbaceous and low- or high-density (33,333
      and 55,556stumps/ha) willow, Salix miyabeana 'SX64', RBS, to minimize leaching of
      glyphosate and its main degradation product (AMPA) from agricultural fields to
      streams. Our study compared triplicate treatments of herbaceous and willow
      planted RBS located in an organic-rich soil at Boisbriand (BB) and in a mineral
      soil at Saint-Roch-de-l'Achigan (SR). Runoff water was sampled with surface
      collectors and interstitial water was collected with 35cm or 70cm tension
      lysimeters. Potential efficiency of the RBS is reported as the percent reduction
      between edge-of-field and edge-of-stream concentrations in runoff and
      interstitial waters. Neither glyphosate nor AMPA in runoff were significantly
      intercepted by the RBS. After field herbicide spraying, glyphosate measured in SR
      surface soils (0-20cm) was on average 210MUg.kg-1 dw (range from undetected to
      <=317MUg.kg-1 dw). Glyphosate was found to be persistent and its infiltration
      towards groundwater may be enhanced by the RBS. Contrary to runoff trends, soil
      glyphosate was significantly less concentrated on the SR edge-of-stream compared
      to edge-of-field (27-54% potential efficiency). The potential efficiency of
      herbaceous, low- and high-density willow RBS were undifferentiated.

PMID- 28505882
TI  - Stemflow-induced spatial heterogeneity of radiocesium concentrations and stocks
      in the soil of a broadleaved deciduous forest.
AB  - The transport of radiocesium from the canopy and quantification of the spatial
      distribution of radiocesium in the soil of konara oak forests are important to
      better understand the variability of 137Cs stocks in the soil between proximal
      and distal stem areas as well as fine-scale variations around the tree trunk.
      Moreover, a better understanding of fine-scale spatial variabilities of 137Cs
      concentrations and stocks will provide insights for optimizing soil sampling
      strategies to provide a more robust estimation of contamination at the stand
      scale. This study aims to elucidate the transport of 137Cs by stemflow in a
      radioactively contaminated konara oak forest in Tsukuba, Japan by describing and
      quantifying the fine-scale spatial distribution of 137Cs in the soil and
      preferential flowpaths of stemflow on the tree stem by a dye tracing experiment.
      137Cs concentrations and stocks were higher in the soils of the proximal stem
      area than distal stem area when they corresponded with the preferential flowpaths
      of stemflow. There was a significant relationship between canopy projection area
      of individual trees and average soil 137Cs concentrations and stocks, even though
      canopies of the trees overlapped. Our results demonstrate that the spatiality of
      137Cs concentrations and stocks in the soil of the proximal stem area are
      governed (at least partially) by the preferential flowpaths of stemflow along the
      tree trunk. In addition, higher 137Cs concentrations and stocks in the near-trunk
      soils of trees with larger crown areas might be caused by an enhanced ability to
      capture dry deposition.

PMID- 28505883
TI  - Spatial patterns and temporal trends of trace metal mass budgets in the western
      Adriatic sediments (Mediterranean Sea).
AB  - Spatial patterns of major (Al, Fe and Ti) and trace metals (Cu, Cr, Mn, Ni, Pb
      and Zn) measured in surficial sediments collected within the Late-Holocene mud
      wedge in the western Adriatic Sea were analyzed to elucidate their sources,
      transport and mass budgets. Distributions of sedimentary trace metals, their
      fluvial inputs and accumulation loads reveal along-shore transport towards the
      southern Adriatic. Pb and to a lower extent Zn accumulation loads over time
      decreased significantly since 1988 in the North Adriatic, consistently with the
      implementation of regulations in the Western Europe, whereas Zn accumulation in
      the Po River prodelta remained unchanged since 1995. The Po River fluvial inputs
      accounted for half of Cr, Ni, Pb and Zn of the fluvial inputs into the western
      Adriatic Sea, contributing for the delivery of important amounts of Cr and Ni
      into the sediments, probably related to the natural occurrence of ultramafic
      rocks in the North sector. Collectively, ~30% of trace metal fluvial inputs
      discharged into the North sector are exported to the Central and South sectors.
      The Po River acts as both a bypass and an accumulation zone. In contrast, trace
      metal accumulation in the Central sector far exceed trace metal fluvial inputs,
      which suggested that this area is a preferential sink for particle-reactive river
      borne material from the North Adriatic. The North sector shows moderate
      enrichment of Zn and Pb mainly related to the Po River influence. The
      anthropogenic fraction of Pb shows a large drop of ~30% from the North sector
      southwards, whereas Zn proportions remain fairly the same up to the Central
      sector only decreasing in the South sector.

PMID- 28505880
TI  - Redox regulation of ischemic limb neovascularization - What we have learned from
      animal studies.
AB  - Mouse hindlimb ischemia has been widely used as a model to study peripheral
      artery disease. Genetic modulation of the enzymatic source of oxidants or
      components of the antioxidant system reveal that physiological levels of oxidants
      are essential to promote the process of arteriogenesis and angiogenesis after
      femoral artery occlusion, although mice with diabetes or atherosclerosis may have
      higher deleterious levels of oxidants. Therefore, fine control of oxidants is
      required to stimulate vascularization in the limb muscle. Oxidants transduce
      cellular signaling through oxidative modifications of redox sensitive cysteine
      thiols. Of particular importance, the reversible modification with abundant
      glutathione, called S-glutathionylation (or GSH adducts), is relatively stable
      and alters protein function including signaling, transcription, and cytoskeletal
      arrangement. Glutaredoxin-1 (Glrx) is an enzyme which catalyzes reversal of GSH
      adducts, and does not scavenge oxidants itself. Glrx may control redox signaling
      under fluctuation of oxidants levels. In ischemic muscle increased GSH adducts
      through Glrx deletion improves in vivo limb revascularization, indicating
      endogenous Glrx has anti-angiogenic roles. In accordance, Glrx overexpression
      attenuates VEGF signaling in vitro and ischemic vascularization in vivo. There
      are several Glrx targets including HIF-1alpha which may contribute to inhibition
      of vascularization by reducing GSH adducts. These animal studies provide a
      caution that excess antioxidants may be counter-productive for treatment of
      ischemic limbs, and highlights Glrx as a potential therapeutic target to improve
      ischemic limb vascularization.

PMID- 28505884
TI  - Experimental studies on combustion of composite biomass pellets in fluidized bed.
AB  - This work presents studies on the combustion of Composite Biomass Pellets (CBPS)
      in fluidized bed using bauxite particles as the bed material. Prior to the
      combustion experiment, cold-flow characterization and thermogravimetric analysis
      are performed to investigate the effect of air velocity and combustion mechanism
      of CBPS. The cold-state test shows that CBPs and bauxite particles fluidize well
      in the fluidized bed. However, because of the presence of large CBPs,
      optimization of the fluidization velocity is rather challenging. CBPs can gather
      at the bottom of the fluidized bed at lower gas velocities. On the contrary, when
      the velocity is too high, they accumulate in the upper section of the fluidized
      bed. The suitable fluidization velocity for the system in this study was found to
      be between 1.5-2.0m/s. At the same time, it is found that the critical
      fluidization velocity and the pressure fluctuation of the two-component system
      increase with the increase of CBPs mass concentration. The thermogravimetric
      experiment verifies that the combustion of CBPs is a first-order reaction, and it
      is divided into three stages: (i) dehydration, (ii) release and combustion of the
      volatile and (iii) the coke combustion. The combustion of CBPs is mainly based on
      the stage of volatile combustion, and its activation energy is greater than that
      of char combustion. During the combustion test, CBPS are burned at a 10kg/h feed
      rate, while the excess air is varied from 25% to 100%. Temperatures of the bed
      and flue gas concentrations (O2, CO, SO2 and NO) are recorded. CBPs can be burnt
      stably, and the temperature of dense phase is maintained at 765-780 degrees C.
      With the increase of the air velocity, the main combustion region has a tendency
      to move up. While the combustion is stable, O2 and CO2 concentrations are
      maintained at about 7%, and 12%, respectively. The concentration of SO2 in the
      flue gas after the initial stage of combustion is nearly zero. Furthermore, NO
      concentration is found to be closely related to O2: the NO reaches its peak value
      after initial stage and later decreases with the continued depletion of O2.
      Towards the end of combustion, NO increases with the increase of O2.

PMID- 28505885
TI  - Occurrence and environmental impact of pharmaceutical residues from conventional
      and natural wastewater treatment plants in Gran Canaria (Spain).
AB  - The presence and fate of pharmaceutical residues in environmental samples are of
      great interest. There is a vast number of studies published regarding their
      input, presence, effects and risks in ecosystems. Moreover, it has been
      demonstrated that the primary source of input of these contaminants in the
      environment is from Wastewater Treatment Plants (WWTPs). It is therefore
      essential to evaluate the efficiency of commonly used treatments and the
      necessity of applying novel purification processes in order to eliminate or
      reduce the concentration of pharmaceuticals from wastewater or from the effluent
      of WWTPs. The aim of this work was to quantify twenty-three pharmaceutical
      compounds in the aqueous phase at different stages of a conventional and a
      natural WWTP situated in Gran Canaria (Spain). The results indicate concentration
      levels in the range of 0.004+/-0.001 to 59.2+/-11.7MUgL-1 and 0.018+/-0.001 to
      148+/-14.7MUgL-1 from conventional and natural WWTPs, respectively. Better
      efficiency was, however, offered by the conventional WWTP with a removal median
      of 99.7%. In addition, the impact on different aquatic organisms (algae, daphnids
      and fish) was assessed in terms of risk quotients. The results reveal a possible
      highly harmful effect towards organisms by gemfibrozil, ibuprofen and ofloxacin.

PMID- 28505886
TI  - Modeling carbon emissions from urban traffic system using mobile monitoring.
AB  - Comprehensive analyses of urban traffic carbon emissions are critical in
      achieving low-carbon transportation. This paper started from the architecture
      design of a carbon emission mobile monitoring system using multiple sets of
      equipment and collected the corresponding data about traffic flow, meteorological
      conditions, vehicular carbon emissions and driving characteristics on typical
      roads in Shanghai and Wuxi, Jiangsu province. Based on these data, the emission
      model MOVES was calibrated and used with various sensitivity and correlation
      evaluation indices to analyze the traffic carbon emissions at microscopic,
      mesoscopic and macroscopic levels, respectively. The major factors that influence
      urban traffic carbon emissions were investigated, so that emission factors of CO,
      CO2 and HC were calculated by taking representative passenger cars as a case
      study. As a result, the urban traffic carbon emissions were assessed
      quantitatively, and the total amounts of CO, CO2 and HC emission from passenger
      cars in Shanghai were estimated as 76.95kt, 8271.91kt, and 2.13kt, respectively.
      Arterial roads were found as the primary line source, accounting for 50.49%
      carbon emissions. In additional to the overall major factors identified, the
      mobile monitoring system and carbon emission quantification method proposed in
      this study are of rather guiding significance for the further urban low-carbon
      transportation development.

PMID- 28505887
TI  - Emission and distribution of phosphine in paddy fields and its relationship with
      greenhouse gases.
AB  - Phosphine (PH3), as a gaseous phosphide, plays an important role in the
      phosphorus cycle in ecosystems. In this study, the emission and distribution of
      phosphine, carbon dioxide (CO2) and methane (CH4) in paddy fields were
      investigated to speculate the future potential impacts of enhanced greenhouse
      effect on phosphorus cycle involved in phosphine by the method of Pearson
      correlation analysis and multiple linear regression analysis. During the whole
      period of rice growth, there was a significant positive correlation between CO2
      emission flux and PH3 emission flux (r=0.592, p=0.026, n=14). Similarly, a
      significant positive correlation of emission flux was also observed between CH4
      and PH3 (r=0.563, p=0.036, n=14). The linear regression relationship was
      determined as [PH3]flux=0.007[CO2]flux+0.063[CH4]flux-4.638. No significant
      differences were observed for all values of matrix-bound phosphine (MBP), soil
      carbon dioxide (SCO2), and soil methane (SCH4) in paddy soils. However, there was
      a significant positive correlation between MBP and SCO2 at heading, flowering and
      ripening stage. The correlation coefficients were 0.909, 0.890 and 0.827,
      respectively. In vertical distribution, MBP had the analogical variation trend
      with SCO2 and SCH4. Through Pearson correlation analysis and multiple stepwise
      linear regression analysis, pH, redox potential (Eh), total phosphorus (TP) and
      acid phosphatase (ACP) were identified as the principal factors affecting MBP
      levels, with correlative rankings of Eh>pH>TP>ACP. The multiple stepwise
      regression model ([MBP]=0.456*[ACP]+0.235*[TP]-1.458*[Eh]-36.547*[pH]+352.298)
      was obtained. The findings in this study hold great reference values to the
      global biogeochemical cycling of phosphorus in the future.

PMID- 28505888
TI  - Fipronil washoff to municipal wastewater from dogs treated with spot-on products.
AB  - Fipronil and fipronil degradates have been reported in treated wastewater
      effluent at concentrations that exceed USEPA Aquatic Life Benchmarks, posing a
      potential risk to the surface waters to which they discharge. Fipronil is a
      common insecticide found in spot-on flea and tick treatment products that have
      the potential for down-the-drain transport and direct washoff into surface water.
      Volunteers currently treating their dogs with a fipronil-containing spot-on
      product were recruited. Dogs were washed either 2, 7, or 28days after product
      application, and rinsate from 34 discrete bathing events were analyzed by LC
      MS/MS for fipronil and fipronil degradates (collectively known as fiproles).
      Total fipronil application dosage ranged from 67.1-410.0mg per dog following
      manufacturers' recommendation based on dog body weight. Total mass of fiproles
      measured in rinsate ranged from 3.6-230.6mg per dog (0.2  86.0% of mass applied).
      Average percentage of fiproles detected in rinsate generally decreased with
      increasing time from initial application: 21+/-22, 16+/-13, and 4+/-5%
      respectively for 2, 7, and 28days post application. Fipronil was the dominant
      fiprole, >63% of total fiproles for all samples and >92% of total fiproles in 2
      and 7day samples. Results confirm a direct pathway of pesticides to municipal
      wastewater through the use of spot-on products on dogs and subsequent bathing by
      either professional groomers or by pet owners in the home. Comparisons of mass
      loading calculated using California sales data and recent wastewater monitoring
      results suggest fipronil-containing spot-on products are a potentially important
      source of fipronil to wastewater treatment systems in California. This study
      highlights the potential for other active ingredients (i.e., bifenthrin,
      permethrin, etofenprox, imidacloprid) contained in spot-on and other pet products
      (i.e., shampoos, sprays) to enter wastewater catchments through bathing
      activities, posing a potential risk to the aquatic organisms downstream of
      wastewater discharge.

PMID- 28505889
TI  - Vegetation dynamics and responses to climate change and human activities in
      Central Asia.
AB  - Knowledge of the current changes and dynamics of different types of vegetation in
      relation to climatic changes and anthropogenic activities is critical for
      developing adaptation strategies to address the challenges posed by climate
      change and human activities for ecosystems. Based on a regression analysis and
      the Hurst exponent index method, this research investigated the spatial and
      temporal characteristics and relationships between vegetation greenness and
      climatic factors in Central Asia using the Normalized Difference Vegetation Index
      (NDVI) and gridded high-resolution station (land) data for the period 1984-2013.
      Further analysis distinguished between the effects of climatic change and those
      of human activities on vegetation dynamics by means of a residual analysis trend
      method. The results show that vegetation pixels significantly decreased for
      shrubs and sparse vegetation compared with those for the other vegetation types
      and that the degradation of sparse vegetation was more serious in the Karakum and
      Kyzylkum Deserts, the Ustyurt Plateau and the wetland delta of the Large Aral Sea
      than in other regions. The Hurst exponent results indicated that forests are more
      sustainable than grasslands, shrubs and sparse vegetation. Precipitation is the
      main factor affecting vegetation growth in the Kazakhskiy Melkosopochnik.
      Moreover, temperature is a controlling factor that influences the seasonal
      variation of vegetation greenness in the mountains and the Aral Sea basin.
      Drought is the main factor affecting vegetation degradation as a result of both
      increased temperature and decreased precipitation in the Kyzylkum Desert and the
      northern Ustyurt Plateau. The residual analysis highlighted that sparse
      vegetation and the degradation of some shrubs in the southern part of the Karakum
      Desert, the southern Ustyurt Plateau and the wetland delta of the Large Aral Sea
      were mainly triggered by human activities: the excessive exploitation of water
      resources in the upstream areas of the Amu Darya basin and oil and natural gas
      extraction in the southern part of the Karakum Desert and the southern Ustyurt
      Plateau. The results also indicated that after the collapse of the Soviet Union,
      abandoned pastures gave rise to increased vegetation in eastern Kazakhstan,
      Kyrgyzstan and Tajikistan, and abandoned croplands reverted to grasslands in
      northern Kazakhstan, leading to a decrease in cropland greenness. Shrubs and
      sparse vegetation were extremely sensitive to short-term climatic variations, and
      our results demonstrated that these vegetation types were the most seriously
      degraded by human activities. Therefore, regional governments should strive to
      restore vegetation to sustain this fragile arid ecological environment.

PMID- 28505890
TI  - Functioning grouped soil microbial communities according to ecosystem type, based
      on comparison of fallows and meadows in the same region.
AB  - Predicting the composition and function of microbial communities at a bio
      geographical scale, across ecosystems, is challenging. We compared six abandoned
      fields to six meadows to see whether soil microbial community structure and
      activity are more similar within the ecosystem type than between the types. We
      implemented bacteria and fungi phylogenetic markers profiling, phospholipids
      analysis, fluorescence counts of total bacteria and algae and microscopy of
      arbuscular mycorrhizal fungi (AMF). The functional performance of microbial
      communities was assessed using enzymes activity measurements as well as culturing
      and incubation experiments. The studied fallows and meadows had similar biomass
      and general structure of soil microbial communities. However, the AMF root
      colonization frequency was higher in the meadows than in the fallows. The AMF
      colonization was promoted in meadows characterised by lower availability of NO3-,
      P and K as well as higher soil pH, which additionally hampered plant acquisition
      of P at the P-limited ecosystem. Fallow and meadow microbial communities showed
      characteristic functional traits. Meadow soils exhibited higher basal respiration
      rate, while cellulose decomposition and nitrogen mineralization were faster in
      fallows. Even when no major differences in community structure could have been
      detected soil microbial communities adapted to local and/or instantaneous
      environmental conditions and formed functionally-specific ecotypes. This work
      points out the relevance of preserving meadows as reservoirs of plant diversity,
      which cope excellent in nutrient depleted conditions and in mountain regions
      thanks to microbial components of ecosystem.

PMID- 28505892
TI  - Re: Oncologic Outcomes of Kidney-Sparing Surgery versus Radical
      Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by
      the EAU Non-Muscle Invasive Bladder Cancer Guidelines Panel.

PMID- 28505891
TI  - Modelling sediment fluxes in the Danube River Basin with SWAT.
AB  - Sediment management is of prior concern in the Danube Basin for provision of
      economic and environmental services. This study aimed at assessing current (1995
      2009) sediment fluxes of the Danube Basin with SWAT model and identifying
      sediment budget knowledge gaps. After hydrologic calibration, hillslope gross
      erosion and sediment yields were broadly calibrated using ancillary data
      (measurements in plots and small catchments, and national and European erosion
      maps). Mean annual sediment concentrations (SSC) from 269 gauging stations (2968
      station-year entries; median 19mg/L, interquartile range IQR 10-36mg/L) were used
      for calibrating in-stream sediments. SSC residuals (simulations-observations)
      median was 2mg/L (IQR -14; +22mg/L). In the validation dataset (172 gauging
      stations; 1457 data-entries, median 17mg/L, IQR 10-28), median residual was 9mg/L
      (IQR -9; +39mg/L). Percent bias in an independent dataset of annual sediment
      yields (SSY; 689 data-entries in 95 stations; median 52t/km2/y, IQR 20
      151t/km2/y) was -21.5%. Overall, basin-wide model performance was considered
      satisfactory. Sediment fluxes appeared overestimated in some regions (Sava and
      Velika Morava), and underestimated in others (Siret-Prut and Romanian Danube),
      but unbiased elsewhere. According to the model, most sediments were generated by
      hillslope erosion. Streambank degradation contributed about 5% of sediments, and
      appeared important in high stream power Alpine reaches. Sediment trapping in
      reservoirs and floodplain deposition was probably underestimated and
      counterbalanced by high stream deposition. Factor analysis showed that model
      underestimations were correlated to Alpine and karst areas, whereas
      underestimations occurred in high seismicity areas of the Lower Danube.
      Contemporary sediment fluxes were about one third of values reported for the
      1980s for several tributaries of the Middle and Lower Danube. Knowledge gaps
      affecting the sediment budget were identified in the contributions of some
      erosion processes (glacier erosion, gully erosion and mass movements), and in
      stream sediment dynamics.

PMID- 28505893
TI  - Re: Robot-Assisted vs Open Adrenalectomy: Evaluation of Cost-Effectiveness and
      Peri-Operative Outcome.

PMID- 28505894
TI  - Re: The Prognostic Significance of the Early Postoperative Neutrophil-to
      Lymphocyte Ratio in Patients with Urothelial Carcinoma of the Bladder Undergoing
      Radical Cystectomy.

PMID- 28505895
TI  - Re: Cytokine Panel for Response to Intravesical Therapy (CyPRIT): Nomogram of
      Changes in Urinary Cytokine Levels Predicts Patient Response to bacillus Calmette
      Guerin.

PMID- 28505896
TI  - Re: Advanced Small Cell Carcinoma of the Bladder: Clinical Characteristics,
      Treatment Patterns and Outcomes in 960 Patients and Comparison with Urothelial
      Carcinoma.

PMID- 28505897
TI  - Re: National Trends in Prostate Biopsy and Radical Prostatectomy Volumes
      following the US Preventive Services Task Force Guidelines against Prostate
      Specific Antigen Screening.

PMID- 28505898
TI  - Re: Mortality among Men with Advanced Prostate Cancer Excluded from the ProtecT
      Trial.

PMID- 28505899
TI  - Re: Urologist-Level Correlation in the Use of Observation for Low- and High-Risk
      Prostate Cancer.

PMID- 28505900
TI  - Re: Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of
      Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1
      Clinical Trial.

PMID- 28505901
TI  - Re: Activation of Notch1 Synergizes with Multiple Pathways in Promoting
      Castration-Resistant Prostate Cancer.

PMID- 28505902
TI  - Re: Robot-Assisted versus Open Radical Prostatectomy: A Contemporary Analysis of
      an All-Payer Discharge Database.

PMID- 28505903
TI  - Re: Androgen Receptor Antagonists Compromise T Cell Response against Prostate
      Cancer Leading to Early Tumor Relapse.

PMID- 28505904
TI  - Re: Spermatogenesis in Tumor-Bearing Testes in Germ Cell Testicular Cancer
      Patients.

PMID- 28505905
TI  - Re: Predictors of Sperm Recovery after Cryopreservation in Testicular Cancer.

PMID- 28505906
TI  - Re: Incidence and Management of Uncomplicated Recurrent Urinary Tract Infections
      in a National Sample of Women in the United States.

PMID- 28505907
TI  - Re: Small Intestine Early Innate Immunity Response during Intestinal Colonization
      by Escherichia coli Depends on its Extra-Intestinal Virulence Status.

PMID- 28505908
TI  - Re: Policies for Replacing Long-Term Indwelling Urinary Catheters in Adults.

PMID- 28505909
TI  - Re: Impact of Hair Removal on Surgical Site Infection Rates: A Prospective
      Randomized Noninferiority Trial.

PMID- 28505910
TI  - Re: A Randomised Phase I/II Trial to Evaluate the Efficacy and Safety of Orally
      Administered Oxalobacter formigenes to Treat Primary Hyperoxaluria.

PMID- 28505911
TI  - Re: Comprehensive Mutagenesis of the FimS Promoter Regulatory Switch Reveals
      Novel Regulation of Type 1 Pili in Uropathogenic Escherichia coli.

PMID- 28505914
TI  - Re: High-Frequency Dusting versus Conventional Holmium Laser Lithotripsy for
      Intrarenal and Ureteral Calculi.

PMID- 28505913
TI  - Re: Progress in Understanding the Genetics of Calcium-Containing Nephrolithiasis.

PMID- 28505912
TI  - Re: The Effect of a Pure Anti-Inflammatory Therapy on Reducing Prostate-Specific
      Antigen Levels in Patients Diagnosed with a Histologic Prostatitis.

PMID- 28505915
TI  - Re: RNA Interference in the Treatment of Renal Stone Disease: Current Status and
      Future Potentials.

PMID- 28505916
TI  - Re: Factors Associated with Compliance in Submitting 24-Hour Urine Collections in
      an Underserved Community.

PMID- 28505917
TI  - Re: A Large Retrospective Series of Pregnancy and Delivery after Midurethral
      Sling for Stress Urinary Incontinence.

PMID- 28505918
TI  - Re: Electronic Bladder Diaries of Differing Duration versus a Paper Diary for
      Data Collection in Overactive Bladder.

PMID- 28505920
TI  - Re: Is Self-Reported Adherence Associated with Clinical Outcomes in Women Treated
      with Anticholinergic Medication for Overactive Bladder?

PMID- 28505919
TI  - Re: OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary
      Incontinence in Women: A Randomized Clinical Trial.

PMID- 28505921
TI  - Re: Workforce Analysis of Female Pelvic Medicine and Reconstructive Surgery, 2015
      to 2045.

PMID- 28505922
TI  - Re: Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse
      Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

PMID- 28505923
TI  - Re: Lower Urinary Tract Symptoms and Metabolic Disorders: ICI-RS 2014.

PMID- 28505924
TI  - Re: Impact of Incontinence on the Quality of Life of Caregivers of Older Persons
      with Incontinence: A Qualitative Study in Four European Countries.

PMID- 28505925
TI  - Re: Ten-Year Prevalence and Incidence of Urinary Incontinence in Older Women: A
      Longitudinal Analysis of the Health and Retirement Study.

PMID- 28505926
TI  - Re: Effectiveness of Solifenacin and Trospium for Managing of Severe Symptoms of
      Overactive Bladder in Patients with Benign Prostatic Hyperplasia.

PMID- 28505927
TI  - Re: Safety and Efficacy of Bipolar versus Monopolar Transurethral Resection of
      the Prostate: A Comparative Study.

PMID- 28505928
TI  - Re: Moxibustion as an Adjuvant for Benign Prostatic Hyperplasia with Lower
      Urinary Tract Symptoms: A Protocol for a Parallel-Group, Randomised, Controlled
      Pilot Trial.

PMID- 28505929
TI  - Re: Interactions between Benign Prostatic Hyperplasia (BPH) and Prostate Cancer
      in Large Prostates: A Retrospective Data Review.

PMID- 28505930
TI  - Re: Testosterone Threshold for Increased Cardiovascular Risk in Middle-Aged and
      Elderly Men: A Locally Weighted Regression Analysis.

PMID- 28505931
TI  - Re: Skin Autofluorescence (a Marker for Advanced Glycation End Products) and
      Erectile Dysfunction in Diabetes.

PMID- 28505932
TI  - Re: Rasch Analysis of the Premature Ejaculation Diagnostic Tool (PEDT) and the
      International Index of Erectile Function (IIEF) in an Iranian Sample of Prostate
      Cancer Patients.

PMID- 28505933
TI  - Re: Self-Reported Sitting Time and Prevalence of Erectile Dysfunction in Japanese
      Patients with Type 2 Diabetes Mellitus: The Dogo Study.

PMID- 28505934
TI  - Re: Hematospermia Evaluation at MR Imaging.

PMID- 28505935
TI  - Re: Sexual Dysfunction among Females Receiving Psychotropic Medication: A
      Hospital-Based Cross-Sectional Study.

PMID- 28505936
TI  - Re: Relationship between Paternal Somatic Health and Assisted Reproductive
      Technology Outcomes.

PMID- 28505937
TI  - Re: Does Abstinence from Ejaculation before Prostate MRI Improve Evaluation of
      the Seminal Vesicles?

PMID- 28505938
TI  - Re: Cancer Risk in First- and Second-Degree Relatives of Men with Poor Semen
      Quality.

PMID- 28505939
TI  - Re: Influence of Increasing Body Mass Index on Semen and Reproductive Hormonal
      Parameters in a Multi-Institutional Cohort of Subfertile Men.

PMID- 28505940
TI  - Re: Treatment with Human, Recombinant FSH Improves Sperm DNA Fragmentation in
      Idiopathic Infertile Men Depending on the FSH Receptor Polymorphism p.N680S: A
      Pharmacogenetic Study.

PMID- 28505941
TI  - Re: Novel Device for Male Infertility Screening with Single-Ball Lens Microscope
      and Smartphone.

PMID- 28505942
TI  - Re: Gaining Coverage in 2014: New Estimates of Marketplace and Medicaid
      Transitions.

PMID- 28505943
TI  - Re: Marketplace Plans with Narrow Physician Networks Feature Lower Monthly
      Premiums than Plans with Larger Networks.

PMID- 28505944
TI  - Re: The Changing Financial Landscape of Renal Transplant Practice: A National
      Cohort Analysis.

PMID- 28505945
TI  - Re: Penile Appearance after Hypospadias Correction from a Parent's Point of View:
      Comparison of the Hypospadias Objective Penile Evaluation Score and Parents
      Penile Perception Score.

PMID- 28505946
TI  - Re: Clinical Pathway for Early Discharge after Complete Primary Repair of
      Exstrophy and Epispadias by Using a Spica Cast.

PMID- 28505947
TI  - Re: Reliance of Preoperative Scrotal Examination versus Final Operative Findings
      in the Evaluation of Non-Palpable Testes.

PMID- 28505949
TI  - Re: Undescended Testis: Level of Knowledge among Potential Referring Health-Care
      Providers.

PMID- 28505948
TI  - Re: Staged Laparoscopic Traction-Orchiopexy for Intraabdominal Testis (Shehata
      Technique): Stretching the Limits for Preservation of Testicular Vasculature.

PMID- 28505950
TI  - Prolotherapy: An effective therapy for Tietze syndrome.
AB  - PURPOSE: To compare the short-term effect of prolotherapy and conservative terapy
      for the Tietze syndrome. PATIENTS AND METHODS: From 2013 to 2014, twenty-one
      patients underwent prolotherapy (group 1) and thirteen underwent conservative
      therapy with analgesics (group 2). A visual analogue score (VAS) was recorded for
      measurement of pain intensity in all patients before (Pre VAS) and after
      injection first day (VAS1), first week (VAS2) and fourth week (VAS3). Group 2
      were received systemic nonsteroidal anti-inflammatory drug. VAS score was
      recorded similarly at the same times (Pre VAS, VAS1, VAS2, VAS3), and clinical
      affects were compared between the two groups. RESULTS: The mean VAS score (mm)
      before prolotherapy was 7.10 in patients who received prolotherapy, and 7.14 mm
      in patients who treated nonsteroidal anti-inflammatory drug. The mean VAS after
      the fist injection was 2.19 mm and dropped to 1.52 mm after the third injection.
      The mean VAS after the nonsteroidal anti-inflammatory drug treatment dropped 2.62
      mm and during the same scores to 3 weeks later. There was no significant
      difference between the group 1 and group 2 in the age, sex and comorbidity. Also
      there was no significant difference between the group 1 and group 2 in clinical
      and radiological evidence. The prolotherapy group showed a faster recovery,
      including significantly reduced clinic findings (p: 0.001). Third VAS is
      significant finding for the prolotherapy group. CONCLUSION: Prolotherapy could be
      performed safely and is a method with a favorable long term treatments for Tietze
      Syndrome. It may be the ideal procedure for patients with drugs side effects and
      advers events especially for those with limited liver and kidney reserve or
      significant comorbidities.

PMID- 28505951
TI  - Reliability of mechanomyographic amplitude measurements for trunk muscles during
      maximal voluntary isometric contraction.
AB  - BACKGROUND: Mechanomyography (MMG) has been used to investigate mechanical
      characteristics of muscle contraction in clinical and experimental settings.
      OBJECTIVE: The aim of this study was to determine the test-retest reliability of
      mechanomyographic amplitude (MMGRMS) measurements as a tool for measuring the
      maximal voluntary isometric contractions (MVICs) of trunk muscles in healthy
      participants. METHODS: There were ten young adults participating in this study.
      Accelerometers were used to detect surface MMG signals from three trials of 5-s
      MVICs of the rectus abdominis, external obliques, erector spinae, and multifidus
      in the vertical, transverse, and longitudinal directions. Intraclass correlation
      coefficient (ICC), standard error of measurement (SEM), and minimum detectable
      change were calculated. RESULTS: Good to excellent test-retest reliability of
      mechanomyographic amplitude (MMGRMS) measurements was achieved for all MVICs of
      trunk muscles in healthy participants, as indicated by ICCs ranging from 0.99 to
      0.64 for MMGRMS of the trunk muscles during MVIC. CONCLUSIONS: This study
      demonstrates that MMG is a reliable measurement to detect the activation
      amplitudes of trunk muscles during MVIC.

PMID- 28505952
TI  - Independent predictors of mortality in subacute and chronic stroke patients: A
      single center study in Turkey.
AB  - BACKGROUND: Although the long-term survival and related predictors have been
      identified in stroke patients, there is little evidence about the mortality rates
      and its associated factors in stroke patients treated in rehabilitation units.
      OBJECTIVE: To evaluate 5-year mortality rates of patients with stroke and its
      relationship with the clinical characteristics after inpatient subacute-chronic
      rehabilitation. METHODS: The files of 1016 stroke patients (482 male, 534 female)
      who received inpatient rehabilitation program were examined retrospectively.
      Patients' characteristics and functional ambulation category were recorded at the
      end of the rehabilitation program. The survival probability was estimated using
      the Kaplan-Meier method and the univariate effects of predictors were determined
      using the log-rank test. The possible factors determined with univariate analyses
      were checked in the Cox regression analysis. RESULTS: A total of 273 patients
      (32%) died within 5 years after stroke. Age (p< 0.001, RR: 1.06, 95% CI: 1.05
      1.08), presence of coronary artery disease (p= 0.003, RR: 1.53, 95% CI: 1.16
      2.03) and poor walking ability (p< 0.001, RR: 2.06, 95% CI: 1.49-2.86) were
      independent prognostic factors for increased mortality. CONCLUSIONS: About one
      third of the rehabilitation patients died within 5 years after stroke. As
      independent ambulation was a strong predictor for long-term survival, it should
      be provided via rehabilitation techniques. Future studies are proposed to
      determine the effects of rehabilitation methods on mortality rates.

PMID- 28505953
TI  - Understanding the complete pathophysiology of chronic mild to moderate neck pain:
      Implications for the inclusion of a comprehensive sensorimotor evaluation.
AB  - BACKGROUND: Inconsistencies in the literature concerning the effect of neck pain
      have led to a lack of understanding concerning the complete pathophysiology of
      neck pain. While the effect of neck pain on motor function as measured by active
      range of motion and isometric neck strength is well documented the effect of neck
      pain on sensory measures such as tactical acuity and neck reposition error (NRE)
      remain poorly understood. OBJECTIVE: The purpose of this study was to evaluate a
      combined sensorimotor evaluation to explore the potential benefits of
      incorporating both sensory and motor task into a physical evaluation of neck pain
      suffers to gain an added knowledge of the complete pathophysiology of their
      health status. METHODS: A cross-sectional study that measured neck joint
      reposition error, tactical acuity, neck isometric strength and range of motion in
      40 volunteer participants (22 pain, 18 control). RESULTS: A statistically
      significant increase in NRE in flexion (2.75?+/- 1.52? vs. 4.53?+/- 1.74? and in
      extension (3.78?+/- 1.95? vs 5.77?+/- 2.73? in participants suffering from neck
      pain was observed. Additionally, the dermatome C5 was found to be the most
      affected. No differences were found in neck strength or neck range of motion
      between healthy controls and patients with chronic moderate neck pain.

PMID- 28505954
TI  - Manipulative rehabilitation applied soon after lumbar disc surgery improves late
      post-operative functional disability: A preliminary 2-year follow-up study.
AB  - BACKGROUND: Studies have shown late post-operative physical disability and
      residual pain in patients following lumbar disc surgery despite growing evidence
      of its beneficial effects. Therefore, rehabilitation is required to minimise the
      late post-operative complications. OBJECTIVE: To assess the feasibility of
      manipulative rehabilitation to improve late post-operative outcomes. METHODS:
      Twenty-one patients aged 25-65 years undergoing lumbar microdiscectomy were
      randomly assigned to the rehabilitation group (n= 14) or active control group (n=
      7) by simple randomisation. Eight rehabilitation sessions were initiated 2-3
      weeks after surgery. Thirty-minute sessions were conducted twice weekly for four
      weeks. Post-operative physical disability and pain were assessed at baseline and
      at the two-year follow-up. RESULTS: Post-operative physical disability improved
      more in patients who had undergone rehabilitation than in those who had received
      control care (63% vs. -23%, P< 0.05). Post-operative residual low back and leg
      pain were alleviated in the treatment group (26% and 57%, respectively), but
      intensified in the control group (-5% and -8%, respectively). CONCLUSIONS: This
      study demonstrated the potential of manipulative rehabilitation and importance of
      post-operative management after lumbar disc surgery. Definitive trials with
      larger sample sizes are required to confirm the feasibility and potential
      therapeutic effectiveness of this approach.

PMID- 28505955
TI  - The immediate effects of manual stretching and cervicothoracic junction
      manipulation on cervical range of motion and upper trapezius pressure pain
      thresholds.
AB  - INTRODUCTION: Myofascial pain is a common impairment treated with various manual
      interventions including spinal thrust manipulation and stretching; however, the
      comparative efficacy of each intervention is uncertain. Therefore, the purpose of
      this investigation was to evaluate thrust manipulation targeting the
      cervicothoracic junction compared to a manual stretch of the upper trapezius
      muscle on cervical range of motion and upper trapezius pressure pain thresholds
      (PPTs). METHODS: Healthy participants with no significant history of neck pain
      were randomized into a thrust manipulation group, a stretching group, or a
      control group. Within group differences were evaluated via a dependent t-test,
      and group by time interactions were evaluated by a two-way repeated measures
      ANOVA. RESULTS: One hundred and two participants were recruited to participate.
      Baseline demographics revealed no significant differences between groups.
      Significant group by time interactions were found for changes in PPTs for both
      the right and left upper trapezius. Also, significant differences were found for
      changes in cervical extension, as well as right and left cervical side bending
      favoring the treatment groups. DISCUSSION: This study demonstrates the potential
      independent effectiveness of spinal thrust manipulation or stretching for
      reducing PPTs at the upper trapezius. Future research should further evaluate the
      limitation of PPTs as a measure of muscle sensitivity as well as factors that may
      contribute to variability in the measurements among individuals seeking care.

PMID- 28505956
TI  - Regression of lumbar disc herniation by physiotherapy. Does non-surgical spinal
      decompression therapy make a difference? Double-blind randomized controlled
      trial.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study determining whether or not Non
      invasive Spinal Decompression Therapy (NSDT) was effective in resorption of
      herniation, increasing disc height in patients with lumbar disc herniation
      (LHNP). METHODS: A total of twenty patients diagnosed as LHNP and suffering from
      pain at least 8 weeks were enrolled to the study. Patients were allocated in
      study (SG) and control groups (CG) randomly. Both groups received combination of
      electrotherapy, deep friction massage and stabilization exercise for fifteen
      session. SG received additionally NSDT different from CG. Numeric Anolog Scale,
      Straight leg raise test, Oswestry Disability Index (ODI) were applied at baseline
      and after treatment. Disc height and herniation thickness were measured on
      Magnetic Resonance Imagination which performed at baseline and three months after
      therapy. RESULTS: Both treatments had positive effect for improving pain,
      functional restoration and reduction in thickness of herniation. Although
      reduction of herniation size was higher in SG than CG, no significant differences
      were found between groups and any superiority to each other (p> 0.05).
      CONCLUSIONS: This study showed that patients with LHNP received physiotherapy had
      improvement based on clinical and radiologic evidence. NSDT can be used as
      assistive agent for other physiotherapy methods in treatment of lumbar disc
      herniation.

PMID- 28505958
TI  - Lateral ankle pain and peroneal tendon subluxation in a patient with peroneal
      quartus muscle and superior peroneal retinaculum injury.

PMID- 28505957
TI  - Spindle cell type malignant peripheral nerve sheath tumor arising in benign
      schwannoma with multiple intraosseous spinal metastasis: A case report.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) arising in benign
      schwannoma with multiple intraosseous spinal metastasis is extremely rare, having
      a highly aggressive progression and poor prognosis. In such cases, the malignant
      cells of MPNST usually have an epithelioid morphology. Here, the authors present
      a very rare case of spindle cell type MPNST arising in benign schwannoma. CASE: A
      47-year-old woman had a history of wide marginal excision of right buttock
      spindle cell sarcoma previously. However, metastatic lesions to C7, L1 body, and
      the right lung were detected during follow-up. Total spondylectomy and
      stabilization of the C7 and L1 tumors were performed within an interval of 5
      months. However, the patient expired 6 months after the last surgery. From
      analysis and study of three tumor specimens (right buttock, cervical and lumbar
      spine), the pathological diagnosis based on histomorphologic and
      immunohistochemical studies was spindle cell sarcoma, high grade, most consistent
      with MPNST arising in schwannoma. RESULTS: It is important that pathologists and
      surgeons recognize that spindle cell type MPNST may arise in benign schwannoma,
      as this recognition aids in assessment of patients with schwannoma and
      contributes to the pathologist making a more precise diagnosis, and the surgeon
      better determining the appropriate therapeutic options and surgical methods.

PMID- 28505959
TI  - The application of a pre-positioned upper cervical traction mobilization to
      patients with painful active cervical rotation impairment: A case series.
AB  - BACKGROUND: Cervical mobilization and manipulation have been shown to improve
      cervical range of motion and pain. Cervical rotatory thrust manipulation has been
      associated with adverse patient reaction and damage to the V3 segment of the
      vertebral artery (VA). OBJECTIVE: To document and describe the effects of an
      upper cervical (UC) traction based mobilization on participants with restricted
      and painful cervical rotation and to document if the mobilization changed blood
      flow velocity through the vertebral artery. METHODS: This case series examined
      the effects of a traction based spinal mobilization on two different groups of
      participants. Group I included 93 participants with restricted bilateral cervical
      rotation that was also painful at end range. Group II included 30 different
      participants whose VA blood flow velocity was examined during the same
      mobilization. Pre- and post-mobilization active cervical rotation, pain intensity
      levels, and VA blood flow velocity during mobilization was documented. RESULTS:
      Paired T-tests were used to determine statistical significance for changes in
      cervical rotation, and VA blood flow velocity during mobilization. Ninety-three
      participants in group I demonstrated an average increase of 16 degrees of
      cervical rotation. No participant demonstrated an increase in pain, and no
      participant in group II (N= 30) demonstrated a change in VA blood flow velocity.
      CONCLUSIONS: The application this UC traction based mobilization improved active
      cervical rotation, end range rotation pain response, did not cause pain during
      its application and did not alter blood flow through the VA during application.

PMID- 28505960
TI  - Normal aging of the lumbar spine in women.
AB  - BACKGROUND: Lumbar lordosis is required for bipedalism. OBJECTIVES: To
      investigate age-related changes in lumbar lordosis and to clarify the
      relationships between lumbar lordosis and vertebral wedging and disc
      degeneration. METHODS: A total of 300 women were included in this retrospective
      study, 50 in each of six age groups (20-, 30-, 40-, 50-, 60- and 70-year-olds).
      Patients with vertebral collapse, instable fracture or disc sequestration were
      excluded. In each patient, lumbar lordosis angle, posterior vertebral wedging, L5
      S1 intervertebral disc angle, L5/L1 vertebral height ratio and L5-S1
      intervertebral disc/L1-L2 intervertebral disc height ratio were examined.
      Significance level was set at p< 0.05 and two-sided tests were used. RESULTS:
      Significant differences were found in lumbar lordosis according to age group (p<
      0.001). Lumbar lordosis correlated most strongly with L4 posterior vertebral
      wedging, L5 posterior vertebral wedging and L5-S1 intervertebral disc angle, in
      that order (r= 0.50, r= 0.40, r= 0.32, respectively; p< 0.001). CONCLUSION: In
      this cohort, strong spinal structure was maintained during physiological aging
      from 20 to 40 years of age; lumbar lordosis increased by 50 years of age.
      Increased lordosis correlated with increased posterior vertebral wedging and loss
      of posterior disc height.

PMID- 28505961
TI  - Effects of dual-task conditions on cervical spine movement variability.
AB  - BACKGROUND: The potential to accurately perform cervical movements during more
      challenging tasks might be of importance to prevent dysfunctional motion
      characteristics. Although sensorimotor function during dual-task conditions are
      of increasing interest in biomedical and rehabilitation research, effects of such
      conditions on movement consistency of the neck have not yet been investigated.
      OBJECTIVE: In this crossover MiSpEx(Medicine in Spine Exercise)-diagnostic study,
      we aimed to explore differences between single and dual-task conditions on
      cervical movement variability. METHODS: Nineteen healthy participants (9 male;
      24.5 +/- 3.3 y) performed 10 repetitive maximal cervical movements in (1)
      flexion/extension and (2) lateral flexion, during one single- and during two dual
      task test conditions (cognitive, motor) in a randomised and cross-over sequence.
      Latter consisted of a working memory n-back task (n= 2) and a repetitive ankle
      movement task. Range of motion (RoM) was assessed using an external three
      dimensional ultrasonic movement analysis system. Coefficient of variation (CV)
      for repetitive RoM was analysed for differences between conditions and controlled
      for variances in intra-individual movement characteristics. RESULTS: Friedman and
      post-hoc Bonferroni-adjusted confidence intervals for differences from single- to
      dual-task values revealed changes in CV in flexion/extension from single-task to
      motor dual-task (+0.02 +/- 0.02 (97.5%CI: 0.01; 0.03); p< 0.05) but not to
      cognitive dual-task condition (+0.01 +/- 0.02 (97.5%CI: 0.003; 0.02)) nor for
      lateral flexion (p> 0.05). Pearson regression analyses revealed a linear negative
      (p< 0.01) influence of CV in flexion/extension on differences from single to both
      cognitive (R=2 0.47) and motor dual-task (R=2 0.55). Results for lateral flexion
      are comparable, baseline CV negatively impacts differences to cognitive (R=2 0.2)
      and motor dual-task performance (R=2 0.76; p< 0.01). CONCLUSIONS: Participants
      with comparable low cervical CV at single-task display a profound increase during
      dual-task conditions while participants with a higher variability remained almost
      stable or showed a decrease. The results point toward a complex interrelationship
      of motion patterns and adaptation processes during challenging tasks in respect
      of cervical CV.

PMID- 28505962
TI  - Assessment of body parameters' symmetry in child violinists.
AB  - BACKGROUND: Playing violin may lead to overload of the locomotor system.
      OBJECTIVE: The aim of this study was to assess body parameters for trunk symmetry
      in child violinists and compare with the control group. METHODS: We analyzed body
      posture of 101 children aged 7-12 years, mean age 11.09 +/- 9.46, 49 child
      violinists and control group of 52 children. RESULTS: We found statistically
      significant differences for the difference in depth of the lower corners of
      scapulae and upper posterior spina iliaca, though greater asymmetries were found
      in the clinical control group. The remaining parameter values are close to
      significance, which may suggest that the process of postural change among the
      children had just started and that the existing asymmetries were easy to correct.
      We found positive correlation between body height and the difference in distance
      of the lower corners of scapulae from the spine: OL (p= 0.029, correlation
      coefficient value was 0.167) and the Thales triangle height: (p= 0.018,
      correlation coefficient was 0.214). CONCLUSIONS: Position maintained while
      playing the violin changed some parameters characterizing the curvature of the
      spine in frontal plane. We found the importance of detailed analysis of children
      body posture and its critical assessment.

PMID- 28505963
TI  - Trunk muscle activation levels during eight stabilization exercises used in the
      functional kinetics concept: A controlled laboratory study.
AB  - BACKGROUND: To ensure accurate implementation of stabilization exercises in
      rehabilitation, physical therapists need to understand the muscle activation
      patterns of prescribed exercise. OBJECTIVE: Compare muscle activity during eight
      trunk and lumbar spine stabilization exercises of the Functional Kinetics concept
      by Klein-Vogelbach. METHODS: A controlled laboratory study with a single-group
      repeated-measures design was utilized to analyze surface electromyographic
      intensities of 14 female and 6 male young healthy participants performing eight
      exercises. Data were captured from the rectus abdominis, external/internal
      oblique and lumbar paraspinalis. The normalized muscle activation levels (maximum
      voluntary isometric contraction, MVIC) for three repetitions during each exercise
      and muscle were analyzed. RESULTS: Side bridging (28 +/- 20%MVIC) and advanced
      planking (29 +/- 20%MVIC) reached the highest activity in the rectus abdominis.
      For external and internal oblique muscles, side bridging also showed the greatest
      activity of 99 +/- 36%MVIC and 52 +/- 25%MVIC, respectively. Apart from side
      bridging (52 +/- 14%MVIC), the supine roll-out (31 +/- 12%MVIC) and prone roll
      out (31 +/- 9%MVIC) showed the greatest activity for the paraspinalis. The
      advanced quadruped, seated back extension and flexion on chair/Swiss Ball, prone
      roll-out and advanced one-leg back bridging only yielded negligible muscle
      activities for the rectus abdominis (< 5%MVIC). CONCLUSION: Based on the data
      obtained, recommendations for selective trunk muscle activation during eight
      stabilization exercises were established, which will guide physical therapists in
      the development of exercises tailored to the needs of their patients.

PMID- 28505965
TI  - Determining the IgM and IgG antibody titer against CMV and helicobacter pylori in
      the serum of multiple sclerosis patients comparing to the control group in
      Hamadan.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease that disables
      central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an
      important role in the MS pathology. The infection with helicobacter pylori also
      is recognized as a protective agent against MS in female. METHODS: Serum samples
      were isolated and frozen at -70?C. The earlier mentioned anti-virus antibodies
      and antibacterial antibodies were quantified by Elisa kit. RESULTS: The results
      showed that IgG antibody average value against cytomegalovirus in the blood of
      multiple sclerosis patients not only decreased but also was significant
      statistically (p< 0.05). IgM and IgG antibodies average value in the blood of
      multiple sclerosis patients against helicobacter pylori shown a statistically
      significant decrease (p< 0.05). CONCLUSION: Therefore it may be considered that
      probably helicobacter pylori presence in the individuals especially in female can
      alleviate MS signs. CMV infection can intensify the symptoms in multiple
      sclerosis patients.

PMID- 28505966
TI  - On the antigen-antibody interaction: A thermodynamic consideration.
AB  - Despite its relevance to many biomedical fields, relatively little effort has
      been put into a comprehensible quantitative description of the effect of reaction
      temperature on the interaction between antigens and their antibodies. In this
      article, a novel, straightforward mathematical model is proposed, which aims to
      describe the effect of temperature on antigen-antibody kinetics. The model
      proposed in this article could hopefully provide clinicians, immunologists, and
      biochemists with an improved insight into the kinetic effect of fluctuations in
      reaction temperature on antigen-antibody-dependent processes and therefore into
      the kinetics of the humoral adaptive immune response.

PMID- 28505968
TI  - Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with
      Longitudinal Changes in Cognition.
AB  - Amyloid deposition occurs in aging, even in individuals free from cognitive
      symptoms, and is often interpreted as preclinical Alzheimer's disease (AD)
      pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD,
      and hypothesized to interact with amyloid-beta (Abeta) in causing cognitive
      decline early in the cascade of AD pathophysiology. Whether and how Abeta and YKL
      40 affect brain and cognitive changes in cognitively healthy older adults is
      still unknown. We studied 89 participants (mean age: 73.1 years) with
      cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments
      from two time-points separated by two years. We tested how baseline levels of
      Abeta42 and YKL-40 correlated with changes in cortical thickness and cognition.
      Thickness change correlated with Abeta42 only in Abeta42+ participants (<600
      pg/mL, n = 27) in the left motor and premotor cortices. Abeta42 was unrelated to
      cognitive change. Increased YKL-40 was associated with less preservation of
      scores on the animal naming test in the total sample (r = -0.28, p = 0.012) and
      less preservation of a score reflecting global cognitive function for Abeta42+
      participants (r = -0.58, p = 0.004). Our results suggest a role for inflammation
      in brain atrophy and cognitive changes in cognitively normal older adults, which
      partly depended on Abeta accumulation.

PMID- 28505967
TI  - NFATc2 Modulates Microglial Activation in the AbetaPP/PS1 Mouse Model of
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-beta
      (Abeta) peptide containing plaques and associated reactive microglia. The
      proinflammatory phenotype of the microglia suggests that they may negatively
      affect disease course and contribute to behavioral decline. This hypothesis
      predicts that attenuating microglial activation may provide benefit against
      disease. Prior work from our laboratory and others has characterized a role for
      the transcription factor, nuclear factor of activated T cells (NFAT), in
      regulating microglial phenotype in response to different stimuli, including Abeta
      peptide. We observed that the NFATc2 isoform was the most highly expressed in
      murine microglia cultures, and inhibition or deletion of NFATc2 was sufficient to
      attenuate the ability of the microglia to secrete cytokines. In order to
      determine whether the NFATc2 isoform, in particular, was a valid immunomodulatory
      target in vivo, we crossed an NFATc2-/- line to a well-known AD mouse model, an
      AbetaPP/PS1 mouse line. As expected, the AbetaPP/PS1 x NFATc2-/- mice had
      attenuated cytokine levels compared to AbetaPP/PS1 mice as well as reduced
      microgliosis and astrogliosis with no effect on plaque load. Although some
      species differences in relative isoform expression may exist between murine and
      human microglia, it appears that microglial NFAT activity is a viable target for
      modulating the proinflammatory changes that occur during AD.

PMID- 28505969
TI  - Early Detection of Learning Difficulties when Confronted with Novel Information
      in Preclinical Alzheimer's Disease Stage 1.
AB  - We employed a highly demanding experimental associative learning test (the AFE-T)
      to explore memory functioning in Preclinical Alzheimer's Disease stage 1 (PreAD
      1) and stage 2 (PreAD-2). The task consisted in the learning of unknown
      object/name pairs and our comprehensive setup allowed the analysis of learning
      curves, immediate recall, long-term forgetting rates at one week, three months,
      and six months, and relearning curves. Forty-nine cognitively healthy subjects
      were included and classified according to the presence or absence of abnormal CSF
      biomarkers (Control, n = 31; PreAD-1, n = 14; PreAD-2, n = 4). Control and PreAD
      1 performances on the experimental test were compared by controlling for age and
      education. These analyses showed clear learning difficulties in PreAD-1 subjects
      (F = 6.98; p = 0.01). Between-group differences in long-term forgetting rates
      were less notable, reaching statistical significance only for the three-month
      cued forgetting rate (F = 4.83; p = 0.03). Similarly, relearning sessions showed
      only statistical trends between the groups (F = 3.22; p = 0.08). In the whole
      sample, significant correlations between CSF Abeta42/tau ratio and the AFE-T were
      found, both in the total learning score (r = 0.52; p < 0.001) and in the three
      month cued forgetting rate (r = -0.38; p < 0.01). Descriptive subanalyses
      involving PreAD-2 suggested greater learning and recall difficulties in these
      subjects when compared with the PreAD-1 group. The present results suggest that
      explicit learning difficulties when binding information could be one of the
      earliest signs of the future emergence of episodic memory difficulties on the
      Alzheimer's disease continuum. Our findings indicate that the AFE-T is a
      sensitive test, capable of detecting subtle memory difficulties in PreAD-1.

PMID- 28505970
TI  - Efficacy of Antidepressants for Depression in Alzheimer's Disease: Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Depression is common in people with Alzheimer's disease (AD)
      affecting overall outcomes and decreasing quality of life. Although depression in
      AD is primarily treated with antidepressants, there are few randomized controlled
      trials (RCTs) assessing efficacy and results have been conflicting. OBJECTIVES:
      To systematically review evidence on efficacy of antidepressant treatments for
      depression in AD. METHODS: Systematic review and meta-analysis of double blind
      RCTs comparing antidepressants versus placebo for depression in AD. We searched
      MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Controlled Trials Register and on
      line national and international registers. Primary outcomes were treatment
      response and depressive symptoms. Secondary outcomes were cognition,
      acceptability, and tolerability. Risk of bias was also assessed. RESULTS: Seven
      studies met inclusion criteria. Three compared sertraline with placebo; one
      compared both sertraline and mirtazapine to placebo; imipramine, fluoxetine, and
      clomipramine were evaluated in one study each. In terms of response to treatment
      (6 studies, 297 patients treated with antidepressants and 223 with placebo), no
      statistically significant difference between antidepressants and placebo was
      found (odds ratio (OR) 1.95, 95% CI 0.97-3.92). We found no significant drug
      placebo difference for depressive symptoms (5 studies, 311 patients, SMD -0.13;
      95% CI -0.49 to 0.24). Overall quality of the evidence was moderate because of
      methodological limitations in studies and the small number of trials. CONCLUSION:
      Despite the importance of depression in people with AD, few RCTs are available on
      efficacy of antidepressants, limiting clear conclusions of their potential role.
      There is a need for further high quality RCTs.

PMID- 28505972
TI  - Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not
      Correlate with CSF Volumes or CSF Production Rate.
AB  - BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by
      accumulation of a 42 amino acid peptide called amyloid-beta (Abeta42) in
      extracellular senile plaques together with intraneuronal inclusions of
      hyperphosphorylated tau protein in neurofibrillary tangles and neuronal
      degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the
      volumes and production rates of which vary considerably between individuals, by
      reduced concentration of Abeta42, increased concentration of phosphorylated tau
      (P-tau) protein, and increased concentration of total tau (T-tau) protein,
      respectively. OBJECTIVE: To examine the outstanding question if CSF
      concentrations of AD associated biomarkers are influenced by variations in CSF
      volumes, CSF production rate, and intracranial pressure in healthy individuals.
      METHODS: CSF concentrations of Abeta42, P-tau, and T-tau, as well as a number of
      other AD-related CSF biomarkers were analyzed together with intracranial
      subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic
      resonance imaging volumetric measurements, and CSF production rate in 19
      cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). RESULTS:
      Negative correlations were seen between the concentrations of three CSF
      biomarkers (albumin ratio, Abeta38, and Abeta40), and ventricular CSF volume, but
      apart from this finding, no significant correlations were observed. CONCLUSION:
      These results speak against inter-individual variations in CSF volume and
      production rate as important confounds in the AD biomarker research field.

PMID- 28505971
TI  - Lipid Peroxidation Markers in Coronary Artery Disease Patients with Possible
      Vascular Mild Cognitive Impairment.
AB  - This study examined associations between lipid peroxidation markers and
      cognition, and associations between these markers and cognitive response to an
      exercise intervention program, in adults with coronary artery disease at risk of
      dementia. Lipid peroxidation products were measured in serum in 118 patients (29
      possible vascular mild cognitive impairment and 89 controls). Ratios of early-
      (lipid hydroperoxides, LPH) to late-stage (8-isoprostane, 8-ISO; 4-hydroxy-2
      nonenal, 4-HNE) lipid peroxidation products were calculated. Cognitive
      performance was assessed before and at completion of a 24-week exercise
      intervention program. A global effect of group on lipid peroxidation markers was
      observed, adjusting for sex, years of education, and cardiopulmonary fitness
      (main effect of group F (3,102) = 2.957, p = 0.036). Lower lipid peroxidation at
      baseline, as determined by lower 8-ISO concentration, was associated with greater
      improvement in verbal memory (F (1, 64) = 4.738, p = 0.03) and executive function
      (F (1, 64) = 5.219, p = 0.026) performance. Similarly, higher ratios of 8-ISO/LPH
      (F (1, 65) = 6.592, p = 0.013) and (8-ISO+4-HNE) to LPH (F (1, 65) = 3.857, p =
      0.054), were associated with less improvement in executive function performance
      over a 24-week exercise intervention. Lipid peroxidation may be a biomarker of
      early vascular cognitive impairment, and elevated lipid peroxidation might limit
      the cognitive benefits of exercise in this high-risk population.

PMID- 28505974
TI  - State of Play in Alzheimer's Disease Genetics.
AB  - Alzheimer's disease (AD), the main form of dementia in the elderly, is the most
      common progressive neurodegenerative disease characterized by rapidly progressive
      cognitive dysfunction and behavior impairment. AD exhibits a considerable
      heritability and great advances have been made in approaches to searching the
      genetic etiology of AD. In AD genetic studies, methods have developed from
      classic linkage-based and candidate-gene-based association studies to genome-wide
      association studies (GWAS) and next generation sequencing (NGS). The
      identification of new susceptibility genes has provided deeper insights to
      understand the mechanisms underlying AD. In addition to searching novel genes
      associated with AD in large samples, the NGS technologies can also be used to
      shed light on the 'black matter' discovery even in smaller samples. The shift in
      AD genetics between traditional studies and individual sequencing will allow
      biomaterials of each patient as the central unit of genetic studies. This review
      will cover genetic findings in AD and consequences of AD genetic findings.
      Firstly, we will discuss the discovery of mutations in APP, PSEN1, PSEN2, APOE,
      and ADAM10. Then we will summarize and evaluate the information obtained from
      GWAS of AD. Finally, we will outline the efforts to identify rare variants
      associated with AD using NGS.

PMID- 28505975
TI  - Reduced Cardiovascular Functions in Patients with Alzheimer's Disease.
AB  - Previous studies have suggested that cardiovascular functions might play a
      critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship
      among heart function, blood flow of cerebral vessels, and AD remains unclear. In
      the present study, AD patients (n = 34) and age- and gender-matched cognitively
      normal controls (n = 34) were recruited. Demographic and comorbidity information
      was collected. The ejection fraction was measured using echocardiography, and the
      mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar
      artery (BA), left terminal internal carotid artery (LTICA), and right terminal
      internal carotid artery (RTICA) were measured using transcranial Doppler. The
      data of lacunae, white matter changes, and plaques in the aortic arch and carotid
      arteries were collected from brain magnetic resonance imaging and computed
      tomography angiography images. Compared with normal controls, AD patients had
      lower ejection fractions and cerebral blood flow velocities and higher RI and PI
      in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid
      arteries. In the multivariate logistic regression analysis, the ejection fraction
      and the mean velocity of the BA and LTICA were independently associated with AD
      after adjusting for age, gender, education, vascular risk factors, arterial
      plaques, and brain ischemic lesions detected in the brain images. These findings
      suggest that heart function and vascular condition may play important roles in AD
      pathogenesis. Improving cardiovascular functions could be a promising approach
      for the prevention and treatment of AD.

PMID- 28505973
TI  - Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The
      Rancho Bernardo Study.
AB  - BACKGROUND: Evidence of a role for vitamin D (VitD) in cognitive aging is mixed
      and based primarily on extreme VitD deficiency. We evaluated the association of
      VitD insufficiency with cognitive function in older, community-dwelling adults
      living in a temperate climate with year-round sunshine. METHODS: A population
      based longitudinal study of 1,058 adults (median age 75; 62% women) who had
      cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD)
      measured in 1997-99 and were followed for up to three additional cognitive
      function assessments over a 12-year period. RESULTS: Overall, 14% (n = 145) of
      participants had VitD insufficiency defined as 25OHD <30 ng/ml. Adjusting for
      age, sex, education, and season, VitD insufficiency was associated with poorer
      baseline performance on the Mini-Mental Status Exam (MMSE) (p = 0.013), Trails
      Making Test B (Trails B) (p = 0.015), Category Fluency (p = 0.006), and Long Term
      Retrieval (p = 0.019); differences were equivalent to 5 years of age. For those
      with VitD insufficiency, the odds of mildly impaired performance at baseline were
      38% higher for MMSE (p = 0.08), 78% higher for Trails B (p = 0.017), and 2-fold
      higher for Category Fluency and Long Term Retrieval (both p = 0.001). VitD
      insufficiency was not related to the rate of cognitive decline on any test or the
      risk of developing impaired performance during follow-up. CONCLUSION: In this
      population with little VitD deficiency, even moderately low VitD was associated
      with poorer performance on multiple domains of cognitive function. Low VitD did
      not predict 12-year cognitive decline. Clinical trials are essential to establish
      a causal link between VitD and cognitive well-being.

PMID- 28505976
TI  - In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of
      Alzheimer's Disease with Diffusion Tensor Imaging.
AB  - A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied
      by severe functional and cognitive decline, is based on clinical findings, with
      final confirmation of the disease at autopsy by the presence of amyloid-beta
      (Abeta) plaques and neurofibrillary tangles. Given that microstructural brain
      alterations occur years prior to clinical symptoms, efforts to detect brain
      changes early could significantly enhance our ability to diagnose AD sooner.
      Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude,
      orientation, and anisotropy of the diffusion of water in tissues, has been used
      to infer neuropathological changes in vivo. Its utility in AD, however, is still
      under investigation. The current study used DTI to examine brain regions
      susceptible to AD-related pathology; the cerebral cortex, entorhinal cortex, and
      hippocampus, in 12-14-month-old 3xTg AD mice that possess both Abeta plaques and
      neurofibrillary tangles. Mean diffusivity did not differ between 3xTg and control
      mice in any region. Decreased fractional anisotropy (p < 0.01) and axial
      diffusivity (p < 0.05) were detected only in the hippocampus, in which both
      congophilic Abeta plaques and hyperphosphorylated tau accumulation, consistent
      with neurofibrillary tangle formation, were detected. Pathological tau
      accumulation was seen in the cortex. The entorhinal cortex was largely spared
      from AD-related neuropathology. This is the first study to demonstrate DTI
      abnormalities in gray matter in a mouse model of AD in which both pathological
      hallmarks are present, suggesting the feasibility of DTI as a non-invasive means
      of detecting brain pathology in vivo in early-stage AD.

PMID- 28505977
TI  - Hippocampal and Clinical Trajectories of Mild Cognitive Impairment with Suspected
      Non-Alzheimer's Disease Pathology.
AB  - Suspected non-Alzheimer's disease pathology (SNAP) characterizes individuals
      showing neurodegeneration (e.g., hypometabolism) without amyloid-beta (Abeta).
      Findings from previous studies regarding clinical and structural trajectories of
      SNAP are inconsistent. Using data from the Alzheimer's Disease Neuroimaging
      Initiative, patients with amnestic mild cognitive impairment (MCI) were
      categorized into four groups: amyloid positive with hypometabolism (Abeta+ND+),
      amyloid only (Abeta+ND-), neither amyloid nor hypometabolism (Abeta-ND-), and
      SNAP (Abeta-ND+). Abeta+ND+(n = 33), Abeta+ND-(n = 32), and Abeta-ND-(n = 36)
      were matched to SNAP for age, gender, apolipoprotein E4 (apoE4) genotype, and
      scores on the Montreal Cognitive Assessment. Elderly controls (n = 40) were also
      matched to SNAP for age, gender, and apoE4 genotype. Longitudinal changes were
      compared across groups in terms of hippocampal volume, clinical symptoms, daily
      functioning, and cognitive functioning over a 2-year period. At baseline, no
      difference in cognition and functioning was observed between SNAP and
      Abeta+groups. SNAP showed worse clinical symptoms and impaired functioning at
      baseline compared to Abeta-ND-and controls. Two years of follow-up showed no
      differences in hippocampal volume changes between SNAP and any of the comparison
      groups. SNAP showed worse functional deterioration in comparison to Abeta-ND-and
      controls. However, Abeta+ND+ showed more severe changes in clinical symptoms in
      comparison to SNAP. Thus, patients with MCI and SNAP showed 1) more severe
      functional deterioration compared to Abeta-ND-and controls, 2) no differences
      with Abeta+ND-, and 3) less cognitive deterioration than Abeta+ND+. Future
      studies should investigate what causes SNAP, which is different from typical AD
      pathology and biomarker cascades.

PMID- 28505978
TI  - An Arabic Version of the Cognitive Subscale of the Alzheimer's Disease Assessment
      Scale (ADAS-Cog): Reliability, Validity, and Normative Data.
AB  - The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) is the
      most widely used instrument for screening cognitive dysfunction in Alzheimer's
      disease. The aim of the present study was to develop an Arabic version of this
      scale (A-ADAS-Cog), examine its psychometric properties (reliability and
      validity), and provide normative data. The A-ADAS-Cog), an Arabic version of the
      Mini-Mental State Examination (A-MMSE), and a Standardized Clinical Dementia
      Rating Scale (CDR) were administered to three Tunisian groups: 124 normal
      controls (NC), 33 patients with non-Alzheimer dementia (N-AD), and 25 patients
      with Alzheimer's disease (AD). The A-ADAS-Cog scores were significantly affected
      by age and education. A correction table was constructed to control these
      effects. The results showed that the A-ADAS-Cog has good internal consistency and
      reliability (alpha= 0.82 for AD). The test-retest reliability of the A-ADAS-Cog
      was stable over time (r = 0.97). An evaluation of the construct validity of the A
      ADAS-Cog using principal component analysis led to a solution with three factors
      (memory, language and praxis), which explained 72% of the variance. The
      concurrent validity of the A-ADAS-Cog was established using the A-MMSE score (r =
      -0.86), CDR Sum of Boxes score (CDR-SB; r = 0.87), and global CDR score (CDR
      Global; r = 0.74). Finally, the A-ADAS-Cog has an excellent discriminating power
      in the diagnosis of AD (ROC area = 0.92). A cut-off score of 10 (sensitivity =
      84% and specificity = 91%) is indicated for the screening of the AD. Overall, the
      results indicated that the A-ADAS-Cog is psychometrically reliable and valid and
      provides promising results for screening of dementia in Arabic speaking patients.

PMID- 28505979
TI  - A Systematic Review and Meta-Analysis of Prevalence Studies of Sporadic Inclusion
      Body Myositis.
AB  - BACKGROUND: Sporadic Inclusion Body Myositis (sIBM) is a rare and slowly
      progressive debilitating muscle disease with symptoms generally developing>=50
      years of age. OBJECTIVE: To conduct a systematic review and meta-analysis of the
      prevalence of sIBM literature, including a methodological quality assessment of
      the selected papers. METHODS: A systematic search of Medline, Embase, Cochrane
      Database of Systematic Reviews and major Myositis and Neurological conferences
      was conducted. Articles reporting prevalence and published in English up to March
      2017 were assessed for methodology quality using the Loney quality assessment,
      Downs & Black score, and the Methodological Evaluation of Observational Research
      checklists. Meta-analyses using random effects were completed on both general
      population and>=50 years prevalence estimates. RESULTS: 315 articles were
      retrieved and data were extracted from 10 relevant studies. One study was
      subsequently excluded due to methodological issues. The meta-prevalence estimate
      from 9 papers was 24.8/1,000,000 (95% CI: 20.0-29.6). The methodological quality
      results were consistent across assessment tools with four articles scoring 4 or 5
      out of 8 in the Loney assessment. The meta-prevalence of these four articles was
      45.6/ 1,000,000 (95% CI: 35.9-55.2). CONCLUSION: There was high variability in
      reported sIBM prevalence estimates and the quality of the studies conducted.
      Existing evidence suggests an increase of prevalence estimates over time, which
      may be explained by growing disease awareness, improvements in diagnostic
      criteria and study methodologies. Further high quality studies are needed to
      understand if prevalence varies across geographies or ethnicities.

PMID- 28505980
TI  - Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular
      Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy.
AB  - Duchenne muscular dystrophy is caused by mutations in DMD which disrupt the
      reading frame. Therapeutic strategies that restore DMD's reading frame, such as
      exon skipping and CRISPR/Cas9, need to be tested in the context of the human DMD
      sequence in vivo. We have developed a novel dystrophic mouse model by using
      CRISPR/Cas9 to delete exon 45 in the human DMD gene in hDMD mice, which places
      DMD out-of-frame. We have utilized this model to demonstrate that our clinically
      relevant CRISPR/Cas9 platform, which targets deletion of human DMD exons 45-55,
      can be directly applied in vivo to restore dystrophin.

PMID- 28505981
TI  - Severe Exacerbation of Myasthenia Gravis Associated with Checkpoint Inhibitor
      Immunotherapy.
AB  - Monoclonal antibodies that target either PD-1 or PD-L1 have recently been
      approved for treatment of advanced non-small cell lung cancer. These antibodies
      are immune checkpoint inhibitors which have been shown to exacerbate Myasthenia
      Gravis (MG) and other autoimmune diseases. While effective in preventing tumor
      cells from evading immune attack, immune checkpoint inhibitors such as nivolumab,
      an antibody directed against the programmed cell death protein-1 (PD-1) receptor
      located on T-cells, may also cause immune dysregulation and could cause or
      potentiate pre-existing autoimmune conditions. We present a patient with latent
      ocular MG treated with nivolumab for her stage IV non-small cell lung cancer who
      developed generalized MG and severe myasthenic crisis. Providers must be aware of
      the risks inherent to these novel therapies since they can have life-threatening
      effects.

PMID- 28505982
TI  - Factors Contributing to Perceived Walking Difficulties in People with Parkinson's
      Disease.
AB  - BACKGROUND: While walking difficulties are common in people with Parkinson's
      disease (PD), little is known about factors that independently contribute to
      their perceived walking difficulties. OBJECTIVE: To identify factors that
      independently contribute to perceived walking difficulties in people with PD.
      METHODS: This study involved 243 (62% men) participants; their mean (min-max) age
      and PD duration were 70 (45-93) and 8 (1-43) years, respectively. A postal survey
      preceded a home visit that included observations, clinical tests, questions and
      questionnaires that were administered as a structured interview. Perceived
      walking difficulties (dependent variable) were assessed with the self
      administered generic Walk-12 (Walk-12G, scored 0-42, higher = worse). Independent
      variables included personal (e.g., age and general self-efficacy) and social
      environmental factors (e.g., social support and living situation) as well as
      disease-related factors including motor (e.g., freezing of gait (FOG) and
      postural instability) and non-motor symptoms (e.g., fatigue and orthostatic
      hypotension). Linear multiple regression analysis was used to identify factors
      that independently contributed to perceived walking difficulties. RESULTS: Eight
      significant independent variables explained 56.3% of the variance in perceived
      walking difficulties. FOG was the strongest significant contributing factor to
      perceived walking difficulties, followed by general self-efficacy, fatigue, PD
      duration, lower extremity function, orthostatic hypotension, bradykinesia and
      postural instability. CONCLUSION: Motor and non-motor symptoms as well as
      personal factors (i.e., general self-efficacy) seem to be of importance for
      perceived walking difficulties in PD. These findings might nurture future
      interventions that address modifiable factors in order to enhance walking ability
      in people with PD.

PMID- 28505984
TI  - On a unique fellow and a good friend: Celebrating the life of Stefan Hesse and
      his contributions to rehabilitation robotics, 1960-2016.

PMID- 28505983
TI  - Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: The Effect of
      Varying Stimulation Parameters.
AB  - Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and
      effective treatment modality for selected patients with Parkinson's disease (PD).
      Since its advent, systematic exploration of the effect of stimulation parameters
      including the stimulation intensity, frequency, and pulse width have been carried
      out to establish optimal therapeutic ranges. This review examines published data
      on these stimulation parameters in terms of efficacy of treatment and adverse
      effects. Altering stimulation intensity is the mainstay of titration in DBS
      programming via alterations in voltage or current settings, and is characterised
      by a lower efficacy threshold and a higher side effect threshold which define the
      therapeutic window. In addition, much work has been done in exploring the effects
      of frequency modulation, which may help patients with gait freezing and other
      axial symptoms. However, there is a paucity of data on the use of ultra-short
      pulse width settings which are now possible with technological advances. We also
      discuss current evidence for the use of novel programming techniques including
      directional and adaptive stimulation, and highlight areas for future research.

PMID- 28505985
TI  - Upper limb robotics applied to neurorehabilitation: An overview of clinical
      practice.
AB  - BACKGROUND: During the last two decades, extensive interaction between clinicians
      and engineers has led to the development of systems that stimulate neural
      plasticity to optimize motor recovery after neurological lesions. This has
      resulted in the expansion of the field of robotics for rehabilitation. Studies in
      patients with stroke-related upper-limb paresis have shown that robotic
      rehabilitation can improve motor capacity. However, few other applications have
      been evaluated (e.g. tremor, peripheral nerve injuries or other neurological
      diseases). PURPOSE: This paper presents an overview of the current use of upper
      limb robotic systems for neurorehabilitation, and highlights the rationale behind
      their use for the assessment and treatment of common neurological disorders.
      CONCLUSIONS: Rehabilitation robots are little integrated in clinical practice,
      except after stroke. Although few studies have been carried out to evaluate their
      effectiveness, evidence from the neurosciences and indications from pilot studies
      suggests that upper limb robotic rehabilitation can be applied safely in various
      other neurological conditions. Rehabilitation robots provide an intensity,
      quality and dose of treatment that exceeds therapist-mediated rehabilitation.
      Moreover, the use of force fields, multi-sensory environments, feedback etc.
      renders such rehabilitation engaging and motivating. Future studies should
      evaluate the effectiveness of rehabilitation robots in neurological pathologies
      other than stroke.

PMID- 28505987
TI  - Improved grasp function with transcranial direct current stimulation in chronic
      spinal cord injury.
AB  - BACKGROUND: Recovering hand function has important implications for improving
      independence of patients with tetraplegia after traumatic spinal cord injury
      (SCI). Transcranial direct current stimulation (tDCS) is a noninvasive
      neuromodulation technique that has potential to improve motor function.
      OBJECTIVE: To investigate the effects of one session of 1 mA, 2 mA, and sham
      anodal tDCS (a-tDCS) in the upper extremity (hand) motor performance (grasp and
      lease) in patients with chronic cervical SCI. METHODS: Eleven participants with
      incomplete SCI were randomized to receive 20 minutes of 1 mA, 2 mA, or sham
      stimulation over the targeted motor cortex over three separated sessions. Hand
      motor performance was measured by a hand robotic evaluation (kinematics) and the
      Box and Blocks (BB) test before and after the stimulation period. RESULTS: A
      significant improvement on the grasp mean to peak speed ratio (GMP) was observed
      in the 2 mA group (pre: 0.38+/-0.02; post: 0.43+/-0.03; mean+/-SEM; p = 0.031).
      There was no statistically significant difference in BB test results, however the
      2 mA intervention showed a positive trend for improvement. CONCLUSIONS: A single
      session of 2 mA of a-tDCS showed gains in hand motor function in patients with
      chronic SCI that were not observed in functional clinical scales. The use of
      robotic kinematics showed promising results in assessing small changes in motor
      performance. Further studies are necessary to determine whether tDCS can be an
      effective long-term rehabilitation strategy for individuals with SCI.

PMID- 28505986
TI  - Combined transcranial direct current stimulation and robotic upper limb therapy
      improves upper limb function in an adult with cerebral palsy.
AB  - BACKGROUND: Robotic therapy can improve upper limb function in hemiparesis.
      Excitatory transcranial direct current stimulation (tDCS) can prime brain motor
      circuits before therapy. OBJECTIVE: We tested safety and efficacy of tDCS plus
      robotic therapy in an adult with unilateral spastic cerebral palsy (USCP).
      METHODS: In each of 36 sessions, anodal tDCS (2 mA, 20 min) was applied over the
      motor map of the affected hand. Immediately after tDCS, the participant completed
      robotic therapy, using the shoulder, elbow, and wrist (MIT Manus). The
      participant sat in a padded chair with affected arm abducted, forearm supported,
      and hand grasping the robot handle. The participant controlled the robot arm with
      his affected arm to move a cursor from the center of a circle to each of eight
      targets (960 movements). Motor function was tested before, after, and six months
      after therapy with the Wolf Motor Function Test (WMFT) and Fugl-Meyer (FM).
      RESULTS: Reaching accuracy on the robot task improved significantly after
      therapy. The WMFT and FM improved clinically meaningful amounts after therapy.
      The motor map of the affected hand expanded after therapy. Improvements were
      maintained six months after therapy. CONCLUSIONS: Combined tDCS and robotics
      safely improved upper limb function in an adult with USCP.

PMID- 28505988
TI  - Intensive seated robotic training of the ankle in patients with chronic stroke
      differentially improves gait.
AB  - BACKGROUND: Robotic driven treatment plans targeting isolated joints of the upper
      limb have improved the sensorimotor condition of patients with stroke. Similar
      intensive efforts to allay lower limb gait impairment have not been so
      successful. In patients with stroke, targeted robot assisted training of the
      ankle joint, in a seated position, has demonstrated significant alterations in
      ankle stiffness and foot-ankle orientation at foot strike which may provide a new
      treatment option for gait impairment. OBJECTIVE: To determine if isolated robot
      assisted training of the ankle joint improves chronic hemiparetic gait in
      patients with stroke who are categorized according to baseline gait impairment.
      METHODS: Patients with chronic stroke (>6mo) and hemiparetic gait (N = 29)
      received 18 sessions of isolated robot-assisted motor training of the ankle
      (3*/week for 6 weeks). All participants had stable clinical baseline scores
      across three admission measures, and no participant was receiving simultaneous
      outpatient rehabilitation. Baseline gait speed determined three impairment
      groups: high, >0.8 m/s; medium, 0.4-0.8 m/s; low, <0.4 m/s. Outcome measures
      included the Berg Balance Scale, the 6 Minute Walk Test, and the 10 Meter Walk
      Test, and were recorded upon admission, discharge, and 3 months following
      intervention. RESULTS: Three distinct and significant between-group patterns of
      recovery emerged for gait speed. The within-group analysis showed that the medium
      and high group exhibited significant improvements in gait speed and endurance
      upon discharge, that were maintained at 3-months. Gait speed improvements were
      clinically significant (>0.16 m/s) for the high function group across all gait
      speed and endurance measures at discharge and at 3 months. The moderate group
      also exhibited clinically significant improvements at follow-up on the 10 Meter
      Walk Test, fast pace (0.16 m/sec), and approached clinical significance for the
      10 Meter Walk comfortable pace (0.12 m/sec). The low group had small but
      significant improvements, at discharge on two of the three gait measures, and
      these improvements were maintained at 3 months. For balance measures, the low and
      moderate impairment groups had significant improvements at discharge that were
      robust on follow-up measure. The high function group demonstrated no significant
      change in balance. CONCLUSIONS: Joint-specific robotic training of the paretic
      ankle provided the most benefit to individuals with moderate or mild gait speed
      impairments after stroke. Baseline gait speed function (low, moderate, high) was
      associated with three distinct recovery profiles. This suggests that severity
      specific intervention may be critical to improving efficiency of stroke recovery.

PMID- 28505989
TI  - Pediatric robotic rehabilitation: Current knowledge and future trends in treating
      children with sensorimotor impairments.
AB  - BACKGROUND: Robot-aided sensorimotor therapy imposes highly repetitive tasks that
      can translate to substantial improvement when patients remain cognitively engaged
      into the clinical procedure, a goal that most children find hard to pursue.
      Knowing that the child's brain is much more plastic than an adult's, it is
      reasonable to expect that the clinical gains observed in the adult population
      during the last two decades would be followed up by even greater gains in
      children. Nonetheless, and despite the multitude of adult studies, in children we
      are just getting started: There is scarcity of pediatric robotic rehabilitation
      devices that are currently available and the number of clinical studies that
      employ them is also very limited. PURPOSE: We have recently developed the MIT's
      pedi-Anklebot, an adaptive habilitation robotic device that continuously
      motivates physically impaired children to do their best by tracking the child's
      performance and modifying their therapy accordingly. The robot's design is based
      on a multitude of studies we conducted focusing on the ankle sensorimotor
      control. In this paper, we briefly describe the device and the adaptive
      environment we built around the impaired children, present the initial clinical
      results and discuss how they could steer future trends in pediatric robotic
      therapy. CONCLUSIONS: The results support the potential for future interventions
      to account for the differences in the sensorimotor control of the targeted limbs
      and their functional use (rhythmic vs. discrete movements and mechanical
      impedance training) and explore how the new technological advancements such as
      the augmented reality would employ new knowledge from neuroscience.

PMID- 28505990
TI  - The features of Gait Exercise Assist Robot: Precise assist control and enriched
      feedback.
AB  - BACKGROUND: In a patient with severe hemiplegia, the risk of the knee giving way
      is high during the early stage of gait exercise with an ankle-foot orthosis.
      However, use of a knee-ankle-foot orthosis has many problems such as large amount
      of assistance and compensatory motions. To resolve these problems, we have
      engaged in the development of the Gait Exercise Assist Robot (GEAR). OBJECTIVE:
      To evaluate the improvement efficiency of walk with GEAR in a stroke patient.
      METHODS: The subject was a 70-year-old man presented with left thalamus
      hemorrhage and right hemiplegia. The patient underwent exercise with the GEAR 5
      days a week, for 40 minutes per day. We evaluated the Functional Independence
      Measure score for walk (FIM-walk score) every week. The control group consisted
      of 15 patients aged 20-75 years with hemiplegia after primary stroke, who had
      equivalent walking ability with the subject at start. As the primary outcome, we
      defined improvement efficiency of FIM-walk, which was gain of FIM-walk divided
      the number of required weeks. RESULTS: Improvement efficiency of FIM-walk of the
      subject was 1.5, while that of control group was 0.48+/-3.2 (mean+/-SD).
      CONCLUSIONS: GEAR is potentially useful for gait exercise in hemiplegic patients.

PMID- 28505991
TI  - Lower extremity robotic exoskeleton training: Case studies for complete spinal
      cord injury walking.
AB  - BACKGROUND: Recent advances in exoskeleton technology has made lower extremity
      powered exoskeletons (LEPE) a viable treatment tool to restore upright walking
      mobility to persons with spinal cord injury (SCI). OBJECTIVE: Evaluate ARKE
      exoskeleton training within a rehabilitation centre environment. METHODS: Case
      studies are presented for two male participants, age 41 and 30, motor complete
      SCI at T6 (N01) and T12 (N02), respectively, as they progress from new LEPE users
      to independent walking. The ARKE 2.0 LEPE (Bionik Laboratories Inc., Toronto,
      Canada) was used for all training (hip and knee powered, forearm crutches,
      control tablet). Data were collected on session times, activity metrics from ARKE
      system logs, and qualitative questionnaire feedback. RESULTS AND CONCLUSION: N01
      required 18, 30-minute training sessions to achieve independent walking. N01
      walked independently within the 12 session target. Foot strikes were frequently
      before the end of the programmed swing phase, which were handled by the ARKE
      control system. Subjective ratings of LEPE learning, comfort, pain, fatigue, and
      overall experience were high for sitting-standing and moderate to high for
      walking. This reflected the complexity of learning to safely walk. Qualitative
      feedback supported the continuation of LEPE use in rehabilitation settings based
      on end-user desire for upright mobility.

PMID- 28505992
TI  - The influence of a constraint and bimanual training program using a variety of
      modalities on endurance and on the cardiac autonomic regulation system of
      children with unilateral cerebral palsy: A self-control clinical trial.
AB  - BACKGROUND: An intensive hybrid program, combining constraint with bimanual
      training, improves upper extremity function as well as walking endurance of
      children with unilateral cerebral palsy (UCP). Endurance improvement may be
      associated with the cardiac autonomic regulation system (CARS) adaptation, known
      to be impaired among these children. OBJECTIVE: To examine the influence of an
      intensive hybrid program on CARS, walking endurance and the correlation with
      upper extremity function of children with UCP. METHODS: Twenty-four children aged
      6-10 years with UCP participated in a hybrid program, 10 days, 6 hours per day.
      Data were collected pre-, post- and 3-months post-intervention. Main outcome
      measures included the Polar RS800CX for heart rate (HR) and heart rate
      variability (HRV) data, the 6-Minute Walk Test (6MWT) for endurance, and the
      Assisting Hand Assessment (AHA) and Jebsen-Taylor Test of Hand Function (JTTHF)
      for bimanual and unimanual function. RESULTS: A significant reduction in HR and
      an increase in HRV at post- and 3-month post-intervention was noted (chi22= 8.3,
      p = 0.016) along with a significant increase in 6MWT with a median increase of 81
      meters (chi22= 11.0, p = 0.004) at the same interval. A significant improvement
      was noted in unimanual and bimanual performance following the intervention.
      CONCLUSIONS: An intensive hybrid program effectively improved CARS function as
      well as walking endurance and upper extremity function in children with UCP
      (213).

PMID- 28505993
TI  - Inter-rater reliability of two-point discrimination in acute stroke patients.
AB  - BACKGROUND: The two-point discrimination (2PD) test is widely used in clinical
      practice to assess tactile acuity and central somatosensory function in stroke
      patients. OBJECTIVES: The aim of this study was to evaluate the reliability of
      2PD test in fingers on the affected and non-affected sides in acute stroke
      patients. METHODS: This was a single group repeated-measures inter-rater
      reliability study. Thirty adults with completed ischemic stroke and left paresis
      participated in the study. Static 2PD sensation was assessed using a standardized
      Dellon discriminator. Two examiners performed measurements of 2PD sensation on
      both hands. Each examiner made three series of measurements at intervals of 1
      minute. After 15 minutes, the study was conducted in the same order by a second
      examiner. RESULTS: The ability for 2PD sensation was significantly reduced in all
      examined fingers on the affected side in comparison to the non-affected side. The
      difference was statistically significant (in each case, p < 0.0001). Inter-rater
      reliability (ICC2,1) for the first measurement at the affected site ranged from
      0.95 to 0.98; at the non-affected site ranged from 0.30 to 0.82. Analysis of the
      average value of three measurements (ICC2,3) yielded values for the affected site
      ranging from 0.98 to 0.99; at the non-affected site ranged from 0.81 to 0.95.
      CONCLUSIONS: The 2PD sensation values for all fingers were higher for the
      affected site in comparison to the non-affected site. Conducting three repeatable
      measurements ensures measurement reliability and repeatability when evaluating
      2PD sensation in fingers on both sides in acute stroke patients.

PMID- 28505994
TI  - Effect of three-dimensional spine stabilization exercise on trunk muscle strength
      and gait ability in chronic stroke patients: A randomized controlled trial.
AB  - BACKGROUND: Three-dimensional spine stabilization exercise can strengthen the
      trunk muscles with minimal spine movement. OBJECTIVE: To investigate the effects
      of the newly developed Spine Balance three-dimensional (3D) system on trunk
      strength and gait abilities of chronic stroke patients. METHODS: Twenty-four
      chronic stroke patients were randomly assigned to an experimental (n = 12) or
      control group (n = 12). The experimental and control groups performed spine
      stabilization exercise by using the newly developed Spine Balance 3D system and
      the well-known Bridge exercise thrice a week for 30 min per day for 7 weeks.
      Timed up and go (TUG) test, 10-m walking test (10-m WT), trunk muscle strength,
      and gait ability were evaluated before and after 7 weeks of intervention.
      RESULTS: The 10-m WT, TUG, walking speed, non-affected side step length, and
      distance in the experimental group, wherein trunk muscle strength was checked by
      using the Spine Balance 3D system evaluation program, showed more significant
      improvement than those in the control group (p < 0.05). CONCLUSION: We suggest
      that the newly developed Spine Balance 3D system can be a more useful therapeutic
      tool for rehabilitation of trunk muscle strength and gait abilities than bridge
      exercise-based spine stabilization exercise in chronic stroke patients.

PMID- 28505995
TI  - Prediction of post-stroke functional mobility from the initial assessment of
      cognitive function.
AB  - BACKGROUND: Cognitive impairment is frequently seen in patients with stroke. The
      possible correlation between cognitive function and functional mobility has been
      proposed; however, the prognostic importance of early cognitive function in
      recovery of mobility has not been investigated in patients with stroke.
      OBJECTIVE: The objective of this study is to investigate whether the cognitive
      function in the acute phase can independently predict the recovery of mobility
      after stroke, and to determine the cut-off value of each cognitive evaluation
      test for community ambulation at six months. METHODS: Seventy two patients
      underwent four domain-specific neuropsychological evaluation tests at about two
      weeks after stroke; these included the word list memory test (WMT), construction
      praxis test (CPT), verbal fluency test (VFT) and Boston naming test (BNT). The
      Functional Ambulation Category (FAC) and ambulatory zone (AZ) at six months after
      stroke were investigated as outcome variables. The domain-specific cognitive
      function, along with other possible predictors for functional mobility, was
      analyzed with regression analysis. RESULTS: The z-scores of WMT (p = 0.018) and
      VFT (p = 0.012) were related to the independence in ambulation. The z-scores of
      VFT (p = 0.006) and CPT (p = 0.009) were predictors for community ambulation,
      with the cut-off values of -2.215 for VFT, and of -0.845 for CPT. CONCLUSIONS:
      Cognitive impairment in the acute phase of stroke can be an independent
      prognostic factor of functional mobility. Domain-specific neuropsychological
      evaluation tests should be considered in the acute phase of stroke to predict the
      recovery of functional mobility.

PMID- 28505996
TI  - Depression one year after hemorrhagic stroke is associated with late worsening of
      outcomes.
AB  - BACKGROUND: Poststroke depression is the most common psychiatric sequelae of
      stroke, and it's independently associated with increased morbidity and mortality.
      Few studies have examined depression after intracranial hemorrhage (ICH).
      OBJECTIVE: To investigate the relationship between depression, ICH and outcomes.
      METHODS: A substudy of the prospective Diagnostic Accuracy of MRI in Spontaneous
      Intracerebral Hemorrhage (DASH) study, we included 89 subjects assessed for
      depression 1 year after hemorrhage. A Hamilton Depression Rating Scale score >10
      defined depression. Univariate, multivariable, and trend analyses evaluated
      relationships between depression, clinical, radiographic, and inflammatory
      factors and modified Rankin score (mRS) at 90 days and one year. RESULTS:
      Prevalence of depression at one year was 15%. Depression was not associated with
      hematoma volumes, presence of IVH or admission NIHSS, nor with demographic
      factors. Despite this, depressed patients had worse 1-year outcomes (p = 0.004)
      and were less likely to improve between 3 and 12 months, and more likely to
      worsen (p = 0.042). CONCLUSION: This is the first study to investigate depression
      one year after ICH. Post-ICH depression was common and associated with late
      worsening of disability unrelated to initial hemorrhage severity. Further
      research is needed to understand whether depression is caused by worsened
      disability, or whether the converse is true.

PMID- 28505997
TI  - Characteristics of individuals seeking activity-based restorative therapy
      following spinal cord injury: A focus on hope.
AB  - BACKGROUND: There is a lack of evidence regarding the psychosocial
      characteristics of individuals with spinal cord injury (SCI) undergoing activity
      based restorative therapy (ABRT) treatment. OBJECTIVES: This study seeks to
      describe the hopefulness of a sample of ABRT participants and describe the
      relationship between hopefulness and level of rehabilitation engagement. METHODS:
      A prospective cross-sectional cohort study was conducted using a convenience
      sample of 73 individuals with SCI (mean time since injury = 66.6 months) seeking
      out-patient, post-acute rehabilitation at a metropolitan ABRT center. Outcome
      measures included a demographic survey, The Hope Scale, the Patient Health
      Questionare-9 and the Hopkins Rehabilitation Engagement Rating Scale. RESULTS:
      The ABRT group reported higher levels of hope (M = 54.78, SD = 7.13) than have
      been reported in a sample of individuals with SCI seeking traditional
      rehabilitation in the acute (M = 24.58, SD = 4.06) setting. Rehabilitation
      engagement was not related to hopefulness in the ABRT group. CONCLUSIONS: The
      ABRT group demonstrated high levels of hopefulness. The difference in hopefulness
      noted between this group and previous studies could be due to the time elapsed
      since injury, the presence of choice in the rehabilitation process, or the
      possibility that individuals who chose to participate in ABRT may have inherently
      different hopefulness characteristics than the broader SCI population.

PMID- 28505998
TI  - "I really hope it comes back" - Olfactory impairment following traumatic brain
      injury: A longitudinal study.
AB  - BACKGROUND: Olfactory impairment (OI) can present in up to 66% of all individuals
      following traumatic brain injury (TBI) and can have significant implications for
      everyday life. OBJECTIVE: To investigate the predictive factors, natural
      progression and consequences of OI following TBI in individuals 12 months post
      injury. METHODS: In this prospective longitudinal study, 37 adults (28 males, 9
      females), mean age 42.3 years (SD 19.4), with predominately severe TBI (mean
      length of posttraumatic amnesia (PTA) 28.6 days, SD 22.6) were assessed using the
      University of Pennsylvania Smell Identification Test (UPSIT). Each participant
      also participated in an open ended interview to allow exploration of their
      experience of having OI. RESULTS: Thirty (83.33%) of the participants
      demonstrated persisting OI at 12 months. Nineteen of these participants
      demonstrated no change in their OI severity category and 4 produced a poorer
      performance. Thirteen participants (36.11%) demonstrated some recovery with 6 of
      these performing within the 'normal' range for age andgender. CONCLUSIONS: OI is
      an enduring impairment for a substantial proportion of individuals who experience
      it following severe TBI. It impacts a range of everyday activities, regardless of
      its severity, and requires comprehensive management during rehabilitation.

PMID- 28505999
TI  - Efficacy of a combined therapeutic approach in the management of Pisa Syndrome.
AB  - BACKGROUND: Pisa syndrome (PS) represents an important source of disability in
      Parkinson's disease (PD). Currently no consensus has been reached on its
      definition or diagnostic criteria, and therapeutic approaches are unspecific and
      often futile. Recently the role of abdominal muscles, and in particular of the
      external oblique (EO), in the pathogenesis of PS was hypothesized. OBJECTIVES: To
      evaluate the role of EO and propose a combined therapeutic approach in the
      management of PS. METHODS: Ten PD patients with PS underwent a combined protocol
      based on repeated lidocaine injection in EO and rehabilitation program. RESULTS:
      Our data confirm the primary role of EO muscles in PS pathogenesis and showed an
      improvement in truncal flexion and balance with a positive impact on patients'
      quality of life after treatment. CONCLUSIONS: These data highlight the need for
      accurate characterization of PS focusing on the role of abdominal muscles and the
      need for a specific rehabilitation protocol for PS management.

PMID- 28506000
TI  - Therapeutic effects of oral dimethyl fumarate on stroke induced by middle
      cerebral artery occlusion: An animal experimental study.
AB  - BACKGROUND: Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective
      characteristics that can be used for treatment of acute ischemic stroke.
      OBJECTIVE: To investigate the therapeutic effects of DMF on histological and
      functional recovery of rats after transient middle cerebral artery (MCA)
      occlusion. METHODS: 22 Sprague-Dawley male rats weighing 275-300 g were
      randomized into three groups by block randomization. In the sham group (n = 7),
      the neck was opened, but neither MCA was occluded, nor any drug was
      administered.The control group (n = 7) was treated with vehicle (methocel) by
      gavage for 14 days after MCA occlusion. In the DMF-treated group (n = 8),
      treatment was performed with 15 mg/kg body weight dimethyl fumarate twice a day
      for 14 days after MCA occlusion. Transient occlusion of the right MCA was
      performed by intraluminal thread method in the DMF-treated and the control group.
      Neurological deficit score (NDS), pole test, and adhesive removal test were
      performed before the surgery, and on post-operative Days 0, 3, 5, 7, 10, and 14.
      After the final behaviour test, the animals' brains were perfused and removed.
      Brains were frozen and sectioned serially and coronally using a cryostat. Infract
      volume and brain volume were estimated by stereology. RESULTS: The percentage of
      infarct volume was significantly lower in DMF-treated animals (5.76%) than in the
      control group (22.39%) (P < 0.0001). Regarding behavioural tests, the DMF-treated
      group showed better function in NDS on Days 7 (P = 0.041) and 10 (P = 0.046), but
      not in pole and adhesive removal tests. There was no significant correlation
      between behavioural tests and histological results. CONCLUSION: Dimethyl fumarate
      could be beneficial as a potential neuroprotective agent in the treatment of
      stroke.

PMID- 28506001
TI  - Motor cortex stimulation does not lead to functional recovery after experimental
      cortical injury in rats.
AB  - BACKGROUND: Motor impairments are among the major complications that develop
      after cortical damage caused by either stroke or traumatic brain injury. Motor
      cortex stimulation (MCS) can improve motor functions in animal models of stroke
      by inducing neuroplasticity. OBJECTIVE: In the current study, the therapeutic
      effect of chronic MCS was assessed in a rat model of severe cortical damage.
      METHODS: A controlled cortical impact (CCI) was applied to the forelimb area of
      the motor cortex followed by implantation of a flat electrode covering the
      lesioned area. Forelimb function was assessed using the Montoya staircase test
      and the cylinder test before and after a period of chronic MCS. Furthermore, the
      effect of MCS on tissue metabolism and lesion size was measured using [18F]
      fluorodesoxyglucose (FDG) MUPET scanning. RESULTS: CCI caused a considerable
      lesion at the level of the motor cortex and dorsal striatum together with a long
      lasting behavioral phenotype of forelimb impairment. However, MCS applied to the
      CCI lesion did not lead to any improvement in limb functioning when compared to
      non-stimulated control rats. Also, MCS neither changed lesion size nor
      distribution of FDG. CONCLUSION: The use of MCS as a standalone treatment did not
      improve motor impairments in a rat model of severe cortical damage using our
      specific treatment modalities.

PMID- 28506002
TI  - Transcranial direct current stimulation combined with visuo-motor training as
      treatment for chronic stroke patients.
AB  - BACKGROUND: Recent studies exploring the combined effect of motor learning and
      transcranial direct current stimulation (tDCS) for stroke rehabilitation have
      shown partially conflicting results. OBJECTIVE: To test the efficacy of an
      optimized hand training approach combined with tDCS in stroke patients. METHODS:
      In the present pilot study we investigated motor effects of four-week training
      with a visuomotor grip force tracking task combined with tDCS in 11 chronic
      stroke patients. Anodal (0.5 mA) or sham tDCS was applied over the primary motor
      cortex of the lesioned side for 20 minutes, twice a day, during training.
      RESULTS: No difference between the Active and Sham groups in the total upper
      extremity (UE) Fugl-Meyer Assessment (FMA) score was found. The most prominent
      recovery occurred in the shoulder-elbow FMA sub-score; in this segment a
      significantly greater improvement in the Active compared to the Sham group was
      observed up to two months after the intervention. Mean hold force during the
      first treatment session predicted the change in the total UE FMA score after
      treatment. CONCLUSION: Four-week visuo-motor training combined with tDCS showed
      no difference between the Active and Sham groups in the total UE FMA score, which
      may be explained by heterogeneity of the degree of recovery in the Active group.
      However, the shoulder-elbow FMA sub-score improved significantly more in the
      Active compared to the Sham group, which deserves further study.

PMID- 28506004
TI  - Relationships between geometrical parameters and mechanical properties for a
      helical braided flow diverter stent.
AB  - BACKGROUND: Although flow diversion is a promising procedure for aneurysm
      treatment, the safety and efficacy of this strategy have not been sufficiently
      characterized. Both mechanical properties and flow reduction effects are
      important factors in the design of an optimal stent. OBJECTIVE: We aimed to
      clarify the contributions of strut size and pitch to the mechanical properties
      (radial stiffness and longitudinal flexibility) and geometric characteristics
      (porosity and pore density) related to flow reduction effects. METHODS: Crimping
      and bending behaviors of the stents were simulated with the finite element
      method. The relationships between the mechanical properties and geometric
      characteristics were investigated by changing the strut size and pitch. RESULTS:
      Within the porosity range of 79-82%, the radial stiffness of the stent was
      similarly influenced by either the strut size or pitch. However, the longitudinal
      flexibility tended to be influenced more by strut size than by pitch.
      CONCLUSIONS: Adjusting the strut size rather than the pitch can change the
      mechanical properties while minimizing the change in porosity or pore density
      related to flow reduction effects.

PMID- 28506003
TI  - Synergy effects of combined multichannel EMG-triggered electrical stimulation and
      mirror therapy in subacute stroke patients with severe or very severe arm/hand
      paresis.
AB  - BACKGROUND: Neurorehabilitation requires the development of severity-dependent
      and successful therapies for arm/hand rehabilitation in stroke patients.
      OBJECTIVE: To evaluate the effectiveness of adding mirror therapy to bilateral
      EMG-triggered multi-channel electrostimulation for the treatment of severe
      arm/hand paresis in stroke patients. METHODS: The subjects of this randomized,
      controlled, multicentre study were stroke patients who had suffered their first
      insult between 1 and 6 months before study start and had severe or very severe
      arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly
      allocated to an intervention group (n = 16) or control group (n = 17). Both
      groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG
      triggered multi-channel electrostimulation. The intervention group additionally
      received mirror feedback of the unaffected limb. The primary outcome measure was
      motor recovery of the upper extremities, as measured by the Fugl-Meyer
      Assessment. RESULTS: The Intervention Group with very severe paresis had
      significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at
      a medium effect size (Cohen) of d = 0.7, due to a significant recovery of
      shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A
      subtest. For subjects with severe paresis, additional mirror therapy did not
      significantly influence outcome. CONCLUSION: Additional mirror therapy in
      combination with EMG-triggered multi-channel electrostimulation is
      therapeutically beneficial for post-acute stroke patients with very severe
      arm/hand paresis.

PMID- 28506005
TI  - Assessment of the dose distribution of Minibeam radiotherapy for lung tumors in
      an anthropomorphic phantom: A feasibility study.
AB  - BACKGROUND: Microbeam radiotherapy (MRT) is a treatment in which radiation field
      is divided into several separate fields of 10-100 MUm width and 100-400 MUm
      spacing. In this treatment, normal tissue can tolerate high doses that are
      delivered to its small volumes. OBJECTIVE: MCNPX 2.4 Monte Carlo code was used to
      calculate the dose distribution of MRT in a lung tumor in a simulated Rando
      phantom. METHODS: The effects of tissue inhomogeneities, using contrast media and
      changing the number of beams were investigated. Dose volume histograms and beam
      profiles of target and organs at risk were assessed and the dose uniformity in
      the target region was evaluated using homogeneity. The conformity indices also
      used to quantify the conformation of the shape of prescribed isodose volume to
      the shape and size of the target. RESULTS: Tissue inhomogeneity of this region
      did not interfere significantly with target dose homogeneity. The use of contrast
      media or increasing the number of beams improved target dose homogeneity and
      decreased the dose to surrounding tissues. CONCLUSIONS: The results suggest that
      further investigation and evaluation of MRT for treatment of chest tumors is
      worthwhile.

PMID- 28506006
TI  - Immediate responses to backpack carriage on postural angles in young adults: A
      crossover randomized self-controlled study with repeated measures.
AB  - BACKGROUND: Heavy backpacks have been associated with various postural changes
      and consequently musculoskeletal disorders. OBJECTIVE: We evaluated the immediate
      responses of varying backpack loads on cranio-vertebral angle (CVA), sagittal
      shoulder angle (SSA) and trunk forward lean (TFL) of young adults between the
      ages of 18-25 years. METHODS: This was a 3*3 cross over randomized controlled
      study with repeated measures among a convenience sample of young adults (n = 30;
      50% male, 50% female). Each participant in a standing posture was assessed at
      four different loads: no backpack, carrying backpack of 5%, 10%, and 15% of body
      weight (BW). A sagittal photograph was taken of the area of the body
      corresponding to spinal angle during each of these test conditions to allow for
      later analysis of postural deviations. Comparisons of the mean deviations of the
      different postural angles from baseline and between test conditions were made
      using ANOVA at p<=0.05. RESULTS: Generally, there was a trend toward a decrease
      in the CVA and TFL with increasing backpack loads. Specifically, a significant
      decrease was seen for TFL at10% and 15% BW loads when compared with no load
      condition. In contrast, the decrease in CVA was only significant between no load
      condition and 15% body weight load. The SSA remained unchanged with backpack
      weight within 15% BW. CONCLUSION: Whereas the SSA of young adults may not be
      upset by an acute loading with a backpack within 15% of body weight, a 15% BW
      backpack led to more forward posture of the head on the neck. In addition,
      backpack load as low as 10% BW is enough to cause an immediate forward lean of
      the trunk.

PMID- 28506007
TI  - Validation study of a Kinect based body imaging system.
AB  - BACKGROUND: Understanding the reliability and precision of the data obtained
      using three-dimensional body scanners is very important if it is intended to
      replace the traditional data collection methods. If the collection of
      anthropometric data with three-dimensional body scanners is a fast and reliable
      process that produces precise data at a low price, it could be used for numerous
      applications worldwide. Many studies have addressed data collected by white light
      and laser based scanners. OBJECTIVE: This study provides a comparative analysis
      between the anthropometric data collected using a Kinect body imaging system with
      the data collected using traditional manual methods. Moreover, a comparison is
      also made between the results obtained in this study and the results of previous
      studies of different types of body scanners. METHODS: The Mean Absolute
      Difference was calculated and all the values were compared to the maximum
      allowable error defined in ISO 20685. Additionally, an analysis of the
      significant differences between the two acquisition methods was also applied to a
      physical mannequin, to understand how the body movement and body stance variation
      in human participants impacts the results obtained. RESULTS: There are few body
      measurements that are close to this restricted allowable error. The results were
      better when the mannequin was measured. Although they were still above the ISO
      20685 limit, they were much closer than the results obtained for human
      participants. CONCLUSION: The main cause of the differences between the two
      methods is the time required for the 3D system to acquire the data. The
      involuntary body sway of human participants is more difficult to control when the
      time span is too long.

PMID- 28506008
TI  - Analysis of air temperature changes on blood pressure and heart rate and
      performance of undergraduate students.
AB  - BACKGROUND: The increase in air temperature has been associated with human
      deaths, some of which are related to cardiovascular dysfunctions, and with the
      reduction of physical and cognitive performance in humans. OBJECTIVE: To analyze
      the relationship between blood pressure (BP) and heart rate (HR) and the
      cognitive performance of students who were submitted to temperature changes in
      classrooms. METHODS: The university students answered a survey that was adapted
      from the Battery of Reasoning Tests over 3 consecutive days at different air
      temperatures while their thermal state and HR were measured. During those 3 days,
      BP and HR were evaluated before and after the cognitive test. RESULTS: The
      average and final HR increased at high temperatures; the tests execution time was
      reduced at high temperatures; and the cognitive tests was related to Mean BP at
      the beginning of the test, the maximum HR during the test and the air
      temperature. CONCLUSIONS: The cognitive performance of undergraduate students in
      the field of engineering and technology will increase while performing activities
      in a learning environment with an air temperature of approximately 23.3 degrees C
      (according to their thermal perception), if students have an initial MBP of 93.33
      mmHg and a 60 bpm HRmax.

PMID- 28506009
TI  - Structural equation model of interactions between risk factors and work-related
      musculoskeletal complaints among Iranian hospital nurses.
AB  - BACKGROUND: Statistics indicate a high risk of developing work-related
      musculoskeletal disorders among hospital nurses. The challenge is to understand
      the associations between musculoskeletal symptoms and various individual and
      occupational risk factors. OBJECTIVE: This study examined the direct and indirect
      interactions of various risk factors with musculoskeletal complaints in hospital
      nurses. METHOD: In a cross-sectional design, Iranian hospital nurses from Semnan
      University of Medical Sciences participated in a questionnaire survey reporting
      their perceived perceptions of various work-related risk factors and
      musculoskeletal symptoms. We tested our proposed structural equation model to
      evaluate the relations between latent and observed concepts and the relative
      importance and strength of exogenous variables in explaining endogenous
      musculoskeletal complaints. RESULTS: Measurement model fits the data relatively
      acceptable. Our findings showed direct effects of psychological, role-related and
      work posture stressors on musculoskeletal complaints. Fatigue mediated the
      adverse indirect relations of psychological, role-related, work posture and
      individual factors with musculoskeletal complaints. CONCLUSIONS: Structural
      equation modeling may provide methodological opportunities in occupational health
      research with a potential to explain the complexity of interactions among risk
      factors. Prevention of work-related musculoskeletal disorders among nurses must
      account for physical and psychosocial conditions.

PMID- 28506010
TI  - Re-evaluation of a LEED Platinum Building: Occupant experiences of health and
      comfort.
AB  - BACKGROUND: There is a need to better understand the perceived experiences of
      workers in green buildings as the literature to this point has been mixed.
      OBJECTIVES: To re-evaluate occupant experiences within a LEED platinum building
      and investigate current experiences in general. METHODS: An online post occupancy
      evaluation (POE) survey of 62 occupants of LEED Platinum building on a US college
      campus is reported. The online survey addressed indoor environmental quality in
      relation to health, productivity and satisfaction. RESULTS: Of the respondents,
      38.7% had participated in a prior POE of this building in 2011 and results were
      compared for this subgroup, as well as for overall results. There was a
      significant increase in satisfaction with office workstations and air freshness
      as compared to 3 years earlier. However, there was also a significant increase in
      reported frequency of all physical symptoms. When looking just at the current POE
      results, control over features of the workstation had a significant relationship
      with most outcomes of interest. CONCLUSION: While improvements have been noted,
      issues continue to exist that have implications for health, productivity and
      satisfaction. The results of this study have implications for the ergonomic
      design of workstations and indoor environmental quality within LEED buildings.

PMID- 28506011
TI  - Unemployment, life satisfaction and deprivation: Gender and partnership
      differences in the context of economic recession.
AB  - BACKGROUND: The economic recession produced a rapid rise of unemployment rates
      that was more visible in Southern European countries. There is evidence that
      unemployment correlates highly with individuals' poor life satisfaction.
      OBJECTIVE: To analyse the relationship between life satisfaction, household
      composition and socioeconomic deprivation in people facing unemployment during
      the economic recession. METHODS: A sample of 748 unemployed people from Lisbon
      (Portugal) completed a socio-demographic questionnaire, the Cantril's ladder of
      life scale, and the latent and manifest benefits of work scale (LAMB). Multiple
      regression analyses were used to test the associations between life satisfaction
      and all other variables. RESULTS: Partnered people report higher life
      satisfaction compared to singles. Financial deprivation and lack of structured
      time were the strongest factors negatively related to life satisfaction in both
      partnered and single people. Having children had a particular negative effect on
      the life satisfaction of partnered men; and living with an unemployed partner
      together with lack of social contact and high enforced activity had a negative
      effect on life satisfaction in partnered women. CONCLUSION: The heterogeneity of
      socioeconomic needs found by household composition bring practical policy
      implications for support actions targeting unemployed individuals in the unique
      context of economic recession.

PMID- 28506012
TI  - I see so I feel: Coping with workplace violence among victims and witnesses.
AB  - BACKGROUND: Workplace violence is a serious concern for workers' mental health
      and well-being in high risk work sectors. OBJECTIVE: This study examined victims'
      and witnesses' experiences after exposure to workplace violence, and the types of
      help they used to cope with the violent event. METHODS: Workers (n = 211) from
      five different work sectors participated in our study. Multiple mediation
      analysis was used to investigate the indirect effects through psychological and
      work consequences on victims' versus witnesses' differential likelihood of using
      formal, paraformal and informal helping. RESULTS: Results showed that workplace
      violence has detrimental effects on both victims and witnesses. Direct victims
      were more negatively affected psychologically and at work than witnesses. The
      indirect effect through psychological difficulty after experiencing workplace
      violence was significant in predicting formal helping. The indirect effect
      through reduced work functioning in predicting paraformal helping was also
      significant. No significant indirect effect was found in predicting informal
      helping. CONCLUSIONS: Both victims and witnesses used multiple types of helping
      to cope with the violent event. This study has practical implications on
      management and clinical practices for better organizations of resources in
      helping victims and witnesses to cope with workplace violence.

PMID- 28506014
TI  - Experiencing violence in a psychiatric setting: Generalized hypervigilance and
      the influence of caring in the fear experienced.
AB  - BACKGROUND: Exposure to violence in the mental health sector both affects
      employees and has implications for the quality of care provided. OBJECTIVE: This
      phenomenological study aims to describe and understand the ways in which acts of
      aggression from a patient might affect workers in a psychiatric institute, their
      relationships with the patients and the services offered. METHODS: Two semi
      structured interviews were conducted with each of the 15 participants from
      various professions within a psychiatric hospital. RESULTS: Our analysis reveals
      four themes: hypervigilance, caring, specific fear toward the aggressor and
      generalized fear of all patients. A state of hypervigilance is found among all
      participants. An emphasis on caring is present among the majority and unfolds as
      a continuum, ranging from being highly caring to showing little or no caring. A
      feeling of fear is expressed and is influenced by the participant's place on the
      caring continuum. Caring workers developed a specific fear of their aggressor,
      whereas those showing little or no caring developed a generalized fear of all
      patients. Following a violent event, caring participants maintained this outlook,
      whereas those demonstrating little to no caring were more inclined to disinvest
      from all patients. CONCLUSIONS: Hypervigilance and fear caused by experiences of
      violence impact the quality of care provided. Considerable interest should thus
      be paid to caring, which can influence fear and its effects.

PMID- 28506013
TI  - The effects of physical training without equipment on pain perception and balance
      in the elderly: A randomized controlled trial.
AB  - BACKGROUND: Research supports a link between exercise and falls prevention in the
      older population. OBJECTIVES: Our aims were to evaluate pain perception and
      balance skills in a group of elderly subjects and to examine the consequences of
      a standardized equipment-free exercise program intervention on these variables.
      The study utilized a randomized controlled trial method. METHODS: 92 subjects
      were recruited from a rural Sicilian village (Resuttano, Sicily, Italy). Subjects
      were randomly split into two groups, an experimental group (EG; n = 49) and a
      control group (CG; n = 43). Qualified fitness instructors delivered the
      standardized physical exercise program for the EG whilst the CG did not receive
      this exercise intervention. The Berg Balance Scale and the Oswestry Disability
      Index were administered in both groups before (T0) and after the intervention
      (T1). RESULTS: At T1, the EG group significantly improvement in balance (p <
      0.0001) and pain perception (p < 0.0001). No significant differences were found
      within the CG both in BBS and ODI, respectively. CONCLUSIONS: Our findings
      suggest that a 13-weeks standardized exercise equipment-free program is effective
      in improving balance and perception of pain in the elderly. This type of
      intervention can consequently provide a low cost strategy to counteract the rate
      of disability in elderly.

PMID- 28506015
TI  - Review on pen-and-paper-based observational methods for assessing ergonomic risk
      factors of computer work.
AB  - BACKGROUND: Computer works are associated with Musculoskeletal Disorders (MSDs).
      There are several methods have been developed to assess computer work risk factor
      related to MSDs. OBJECTIVE: This review aims to give an overview of current
      techniques available for pen-and-paper-based observational methods in assessing
      ergonomic risk factors of computer work. METHODS: We searched an electronic
      database for materials from 1992 until 2015. The selected methods were focused on
      computer work, pen-and-paper observational methods, office risk factors and
      musculoskeletal disorders. This review was developed to assess the risk factors,
      reliability and validity of pen-and-paper observational method associated with
      computer work. Two evaluators independently carried out this review. RESULTS:
      Seven observational methods used to assess exposure to office risk factor for
      work-related musculoskeletal disorders were identified. The risk factors involved
      in current techniques of pen and paper based observational tools were postures,
      office components, force and repetition. From the seven methods, only five
      methods had been tested for reliability. They were proven to be reliable and were
      rated as moderate to good. For the validity testing, from seven methods only four
      methods were tested and the results are moderate. CONCLUSION: Many observational
      tools already exist, but no single tool appears to cover all of the risk factors
      including working posture, office component, force, repetition and office
      environment at office workstations and computer work. Although the most important
      factor in developing tool is proper validation of exposure assessment techniques,
      the existing observational method did not test reliability and validity.
      Futhermore, this review could provide the researchers with ways on how to improve
      the pen-and-paper-based observational method for assessing ergonomic risk factors
      of computer work.

PMID- 28506016
TI  - Comparison of the strength endurance parameters for the Baltimore Therapeutic
      Equipment (BTE) Simulator II and the Jamar Handgrip Dynamometer.
AB  - BACKGROUND: The purpose of this study was to provide evidence regarding the
      Baltimore Therapeutic Equipment (BTE) Work Simulator II's recommended grip
      endurance protocol. The grip endurance protocol of the BTE Simulator II has never
      been validated, though it has been used often for the rehabilitation of work
      related injuries and other occupational dysfunctions. Without validation, the
      grip endurance protocol may or may not be providing skilled clinicians with
      appropriate evaluation results. This study evaluated a protocol comparing the BTE
      Simulator II to the Jamar Dynamometer to determine how the BTE compares to the
      Jamar device. OBJECTIVE: To establish whether the recommended grip endurance
      protocol for the BTE Simulator II is comparable to the parameters established for
      the Jamar handgrip dynamometer. METHODS: Data were gathered from 140 participants
      ages 18 to 40 at the time of the study. Participants completed protocols
      established for the BTE Simulator II and compared to a performance of a grip
      strength endurance protocol for the Jamar Handgrip Dynamometer. After
      establishing baseline strength levels for the participants, they were timed to
      see how long they could sustain a 30% maximum voluntary contraction (MVC) on each
      device. Sample t-tests were calculated to compare the results of the BTE
      Simulator II to the previously validated Jamar device. RESULTS: A dependent
      sample t-test found no statistically significant difference between the times a
      participant sustained 30% of their maximum voluntary contraction (MVC) on the BTE
      Simulator II with attachment #162 versus the Jamar Dynamometer when comparing the
      differences of the means. This provides possible evidence of validity for the BTE
      endurance protocol. The independent sample t-test found no statistically
      significant difference between the grip endurance of the males versus the
      females, however, the means indicate men sustained 30% of their MVC longer than
      their female counterparts on the BTE. CONCLUSIONS: The findings indicate that the
      30% MVC may be a reliable baseline for grip strength endurance testing following
      the BTE Simulator II protocol. This suggests that the BTE Simulator II's
      endurance protocol may be a useful tool to document client progression during
      rehabilitation after sustaining an upper extremity dysfunction. Further research
      is needed to validate this protocol using different populations.

PMID- 28506017
TI  - Prevalence of serious psychological distress among slaughterhouse workers at a
      United States beef packing plant.
AB  - BACKGROUND: Workers in the animal slaughter and processing industry in the United
      States experience high rates of occupational injury as well as stressful work
      conditions, yet mental health in this workforce remains largely unstudied.
      OBJECTIVE: To assess prevalence of serious psychological distress (SPD) in a
      sample of industrial US slaughterhouse workers. PARTICIPANTS: Workers at an
      industrial beef packing plant in Nebraska, United States (n = 137). METHODS: We
      interviewed workers using the Kessler-6, a well-validated measure of non-specific
      anxiety disorders, to assess SPD. We compared SPD prevalence with national
      estimates from 2009 CDC's Behavioral Risk Factor Surveillance Study. RESULTS:
      Prevalence of SPD among workers was 4.4%, compared to United States population
      wide prevalence of 3.6%. Prevalence of mild and moderate psychological distress
      among these workers (14.6%) was also higher than national estimates. Recent
      occupational injury, work area and job activities were not associated with
      elevated prevalence of SPD. Non-Hispanic white workers experienced elevated
      prevalence of SPD compared to Hispanic or Latino workers (prevalence odds ratio:
      6.4; CI: 1.3, 30.5; p = 0.012). CONCLUSION: Workers at a US industrial
      slaughterhouse experienced higher prevalence of SPD compared to United States
      population-wide estimates, but occupational risk factors for this outcome were
      not identified.

PMID- 28506018
TI  - Return to work predictors of stroke survivors and their spousal caregivers.
AB  - BACKGROUND: Return to work is an issue of concern for stroke survivors and their
      spouses. Ramifications may include loss of income and self-efficacy. OBJECTIVE:
      This study describes the return to work patterns of stroke survivors and their
      spousal caregivers post stroke. METHODS: One hundred fifty-nine dyads were
      examined for their return to work patterns at baseline (post hospital discharge)
      and then at 3 month intervals for one year. Relationships were determined between
      work and gender, age, ethnicity, education, type of insurance, type of stroke,
      location of stroke, motor and cognitive functional status, depression, mutuality,
      and life satisfaction. RESULTS: Low levels of return to work by stroke survivors
      (7.5%) and a small decrease in the amount of working caregivers (from 45.3% to
      40.35%) were found one year post baseline. Variables that predicted return to
      work changed over the five data points except for younger age for the caregiver,
      which was consistently significant across all data points. Three case scenarios
      representative of working patterns are offered. CONCLUSIONS: Further research is
      needed regarding the return to work needs of stroke survivors and their spousal
      caregivers, particularly what role the occupational therapist may play in
      facilitating that process.

PMID- 28506020
TI  - Rigid motion artifact reduction in CT using frequency domain analysis.
AB  - BACKGROUND: It is often unrealistic to assume that the subject remains stationary
      during a computed tomography (CT) imaging scan. A patient rigid motion can be
      decomposed into a translation and a rotation around an origin. How to minimize
      the motion impact on image quality is important. OBJECTIVE: To eliminate
      artifacts caused by patient rigid motion during a CT scan, this study
      investigated a new method based on frequency domain analysis to estimate and
      compensate motion impact. METHODS: Motion parameters was first determined by the
      magnitude correlation of projections in frequency domain. Then, the estimated
      parameters were applied to compensate for the motion effects in the
      reconstruction process. Finally, this method was extended to helical CT. RESULTS:
      In fan-beam CT experiments, the simulation results showed that the proposed
      method was more accurate and faster on the performance of motion estimation than
      using Helgason-Ludwig consistency condition method (HLCC). Furthermore, the
      reconstructed images on both simulated and human head experiments indicated that
      the proposed method yielded superior results in artifact reduction. CONCLUSIONS:
      The proposed method is a new tool for patient motion compensation, with a
      potential for practical application. It is not only applicable to motion
      correction in fan-beam CT imaging, but also to helical CT.

PMID- 28506021
TI  - Metal artifact reduction in spiral fan-beam CT using a new sinogram segmentation
      scheme.
AB  - Objective of this study is to present and test a new method for metal artifact
      reduction (MAR) by segmenting raw CT data (sinogram). The artifact suppression
      technique incorporates two steps namely, metal projection segmentation in the
      sinogram and replacement of segmented regions by new values using an
      interpolation method. The proposed segmentation algorithm uses the sinogram
      instead of reconstructed CT slices. First, one of the best and newest region
      based geometric active contour models is used to detect projection data affected
      by metal objects (missing projections). Then, the Hough-transform method is
      applied to detect all sinusoidal-like curves belonging to metal objects. Finally,
      a post image processing technique is used aiming to increase accuracy of the
      segmentation process. To provide a proof of performance, CT data of two patients
      with metallic teeth filling and pelvis prosthesis were included in the study as
      well as CT data of a phantom with metallic teeth inserts. Accuracy was determined
      by comparing mean, variance, mean squared error (MSE) and, peak signal to noise
      ratio (PSNR) as evaluation measurements of distortion in phantom images with
      respect to metallic teeth (original and suppressed) and without metallic teeth
      inserts. Quantitative results showed an average improvement of 12 dB in terms of
      PSNR and 517 in terms of MSE when the new MAR method was applied to remove metal
      artifacts. Qualitative improvement was also assessed by comparing uncorrected
      clinical images with artifact suppressed images. Moreover, qualitative comparison
      of the results of the proposed new method with the existing methods of MAR showed
      the superiority of the new method tested in this study.

PMID- 28506022
TI  - Breast osteoblastoma and recurrence after resection: Demonstration by color
      Doppler ultrasound.
AB  - Osteoblastoma is a rare benign primary bone tumor, which occurs in any part of
      the skeleton. Extraskeletal osteoblastoma is rather rare. We presented an
      extremely rare case of extraskeletal osteoblastoma located in the breast. The
      tumor recurred 7 months later after resection and transformed to aggressive
      osteoblastoma. The histopathological features, ultrasonic manifestations and
      ultrasonic differential diagnoses of the primary and recurrent tumors were
      discussed. The recommended treatment of the tumor is surgical excision. Due to
      its tendency of recurrence and potential malignant transformation, adequate
      resection and careful follow up is essential.

PMID- 28506023
TI  - Optimization method of MRI scan parameters of a double inversion recovery
      sequence using a T1 map and a developed analysis algorithm.
AB  - BACKGROUND: Optimizing scan parameters for double inversion recovery (DIR)
      sequences remains difficult. OBJECTIVE: To evaluate a new method for optimizing
      DIR sequence scan parameters using T1 mapping and a newly developed analysis
      algorithm. METHODS: Twelve healthy volunteers underwent T1 mapping and DIR
      magnetic resonance imaging. The following steps were used for image optimization
      including: 1) measurement of gray matter (GM), white matter (WM), and
      cerebrospinal fluid (CSF) T1 values to create a T1 map; 2) calculation of
      optimized scan parameters by using a developed analysis algorithm; 3) performance
      assessment of DIR magnetic resonance imaging by using the calculated optimized
      imaging parameters. Additionally, we used scan parameters from previous studies
      to obtain DIR images in order to evaluate our new method. The contrast between GM
      and suppressed tissues was compared between these images and those obtained using
      the optimized parameters. RESULTS: Using our optimization method, WM and CSF
      regions were suppressed uniformly for all scan conditions. The contrast was
      significantly higher in images obtained using this optimization method compared
      to those obtained using previously published parameters (p < 0.01). CONCLUSIONS:
      It is possible to obtain superior DIR images by using an optimization method that
      involves T1 mapping and a newly developed analysis algorithm.

PMID- 28506024
TI  - MicroRNA expression profiling in endometriosis-associated infertility and its
      relationship with endometrial receptivity evaluated by ultrasound.
AB  - OBJECTIVE: To investigate the microRNA expression profiling in endometriosis
      associate infertility, and relationship between the microRNA expression and
      endometrial receptivity evaluated by ultrasound. METHODS: First, miRNA expression
      profiling difference of ectopic endometrium between 8 endometriosis patients and
      6 endometriosis-free patients were compared. Bioinformatics analyses detected 61
      differentially expressed (DE) known miRNAs and 57 DE novel miRNAs. Next, other 24
      patients were selected for checking the microRNAs in differential expression by
      RT-PCR. Among them, case and control groups include 14 endometriosis and 10
      endometriosis-free infertility patients, respectively. Last, endometrial
      receptivity of other 20 endometriosis patients was evaluated by ultrasound. In
      this group of patients, 12 had high endometrial receptivity, in which infertility
      is caused by fallopian tube occlusion, and 8 had low endometrial receptivity. The
      study compared endometrial miRNAs expression between two groups, and also
      evaluated the relationship between the endometrial miRNAs expression and the
      endometrial receptivity. RESULTS: First, study indicated that "proteinaceous
      extracellular matrix," "laminin binding" and "extracellular matrix binding" were
      enriched in 6 up-regulated miRNA targets, while "cell proliferation" was enriched
      in the 4 down-regulated miRNA targets. Second, 10 miRNAs in different expression
      (miR-1304- 3p, miR-544b, miR-3684, miR-494-5p, miR-4683, miR-6747-3p; miR-3935,
      miR-4427, miR-652-5p, miR-205-5p) were detected by RT-PCR, and the results showed
      statistically significant differences between 2 groups in all 10 miRNAs. Third,
      the expression levels of miR-1304-3p, miR-494-5p, and miR-4427 were different
      between the two groups with different endometrial receptivity. But for the miR
      544b, there was no statistically significant difference between two groups.
      CONCLUSIONS: The study provided a comprehensive understanding to the current
      knowledge in the field of miRNAs in endometriosis and the relationship between
      them and the endometrial receptivity. miRNAs could be used as diagnostic
      biomarkers and therapeutic agents for this disease. The combination of ultrasound
      and miRNAs detection could be a better choice for the diagnosis of infertility in
      the future.

PMID- 28506025
TI  - Modified Pechini Processing of Barium and Lanthanum-Lithium Titanate
      Nanoparticles and Thin Films.
AB  - Barium-strontium titanate (BST) Ba0.6Sr 0.4 TiO3 and lanthanum-lithium titanate
      (LLT) La0.5Li0.5TiO3 nanopowders and thin films have been obtained via the
      modified Pechini route. Polyesterification and complexation processes of gel
      formation have been examined. Hypothetical models of coordinative polymers formed
      in sol-gel system have been suggested. It has been shown that BST and LLT solid
      solutions form in one step at relatively low temperature. X-ray diffraction
      confirms that the final products, which are single phases and have cubic shape,
      are formed at 600 and 700  degrees C for BST and LLT respectively. It has been
      found that use of thermal shock as pretreatment allows to increase the density of
      BST- and LLT-based thin films.

PMID- 28506026
TI  - Raman Submicron Spatial Mapping of Individual Mn-doped ZnO Nanorods.
AB  - ZnO nanorods (NRs) arrays doped with a large concentration of Mn synthesized by
      aqueous chemical growth and were characterized by SEM, photoluminescence, Raman
      scattering, magnetic force microscopy (MFM). By comparison of spectra taken on
      pure and Mn-doped ZnO NRs, a few new Raman impurity-related phonon modes,
      resulting from the presence of Mn in the investigated samples. We also present a
      vibrational and magnetic characterization of individual lying nanorods using
      Raman and MFM imaging. Confocal scanning micro-Raman mapping of the spatial
      distribution of intensity and frequency of phonon modes in single Mn-doped ZnO
      NRs nanorods is presented and analyzed for the first time. Mn-related local
      vibrational modes are also registered in Raman spectra of the single nanorod,
      confirming the incorporation of Mn into the ZnO host matrix. At higher Mn
      concentration the structural transformation toward the spinel phase ZnMn2O4 and
      Mn3O4 is observed mainly in 2D bottom layers. MFM images of Mn-doped ZnO NR
      arrays and single nanorod were studied in nanoscale at room temperature and
      demonstrate magnetic behavior. The circular domain magnetic pattern on top of
      single nanorod originated to superposition of some separate domains inside rod.
      This demonstrates that long-range ferromagnetic order is present at room
      temperature. Aligned Mn-doped ZnO NRs demonstrates that long-range ferromagnetic
      order and may be applied to future spintronic applications.

PMID- 28506027
TI  - Final Report of Unmet Needs of Interferon-Based Therapy for Chronic Hepatitis C
      in Korea: Basis for Moving into the Direct-Acting Antiviral Era.
AB  - Background/Aims: To evaluate the era of direct acting antivirals (DAAs), we must
      understand the treatment patterns and outcomes of interferon-based therapy for
      hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate,
      factors affecting treatment decisions, and efficacy of interferon- based therapy
      in a real-world setting. Methods: This nationwide cohort study included 1,191
      newly diagnosed patients with chronic HCV infection at seven tertiary hospitals
      in South Korea. Subjects were followed retrospectively until March 2015, which
      was just before the approval of DAA therapy. Results: In total, 48.2% and 49.3%
      of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy
      was initiated in 541 patients (45.4%). The major reasons for no treatment
      included ineligibility (18.9%), concern about adverse events (22.3%), cost
      (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued
      (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found
      that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients
      and 74.7% in nongenotype 1 patients. Conclusions: Approximately one-third of
      newly diagnosed HCV patients in South Korea received interferon-based therapy and
      showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a
      less advanced liver status and reducing the DAA therapy cost may fulfill unmet
      needs.

PMID- 28506029
TI  - Establishment of a Disease-Specific Graded Prognostic Assessment for
      Hepatocellular Carcinoma Patients with Spinal Metastasis.
AB  - Background/Aims: Hepatocellular carcinoma (HCC) patients with spinal metastasis
      (SM) show heterogeneous lengths of survival. In this study, we develop and
      propose a graded prognostic assessment for HCC patients with SM (HCC-SM GPA).
      Methods: We previously reported the outcomes of 192 HCC patients with SM who
      received radiotherapy from April 1992 to February 2012. Prognostic factors that
      significantly affected survival in that study were used to establish the HCC-SM
      GPA. Validation was performed using an independent cohort of 63 patients
      recruited from September 2011 to March 2016. Results: We developed the HCC-SM GPA
      using the following factors: Eastern Cooperative Oncology Group performance
      status (0-2, 0 point; 3-4, 1 point), controlled primary HCC (yes, 0 point; no, 2
      points), and extrahepatic metastases other than bone (no, 0 point; yes, 1 point).
      Patients were stratified into low (GPA=0), intermediate (GPA=1 to 2), and high
      risk (GPA=3 to 4). When applied to the validation cohort, the HCC-SM GPA
      determined median survival durations of 13.6, 4.8, and 2.6 months and 1-year
      overall survival rates of 58.3%, 17.8%, and 7.3% for the low-, intermediate-, and
      high-risk patient groups, respectively (p<0.001). Conclusions: Our newly proposed
      HCC-SM GPA successfully predicted survival outcomes.

PMID- 28506028
TI  - Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using
      Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists for Prophylaxis
      and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis.
AB  - Background/Aims: Although proton pump inhibitors (PPIs) have been widely used for
      the prevention and treatment of stress gastric ulcers in hospital settings, there
      are concerns that PPIs increase the risk of Clostridium difficile infection
      (CDI). However, little is known about the risk of CDI following PPI and histamine
      2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired
      CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs.
      Methods: A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing
      and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through
      August 19, 2016, identified 12 studies that reported the hospital-acquired CDI
      occurrence following H2RA and PPI use for the prevention and treatment of stress
      gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals
      were estimated. Heterogeneity was measured using I2, and a meta-regression
      analysis was conducted. The Grading of Recommendations Assessment, Development,
      and Evaluation (GRADE) system was used to assess the overall quality of the
      evidence. Results: A total of 74,132 patients from 12 observational studies were
      analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds
      ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I2=42.81%).
      Subgroup analyses of the purpose of study medication use, study site, and study
      design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs.
      The overall quality of evidence was rated as low. Conclusions: The use of PPIs
      for both the prevention and treatment of stress ulcers was associated with a
      38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.

PMID- 28506031
TI  - Identification and Characterization of Protein Arginine Methyltransferase 1 in
      Acanthamoeba castellanii.
AB  - Protein arginine methyltransferase (PRMT) is an important epigenetic regulator in
      eukaryotic cells. During encystation, an essential process for Acanthamoeba
      survival, the expression of a lot of genes involved in the encystation process
      has to be regulated in order to be induced or inhibited. However, the regulation
      mechanism of these genes is yet unknown. In this study, the full-length 1,059 bp
      cDNA sequence of Acanthamoeba castellanii PRMT1 (AcPRMT1) was cloned for the
      first time. The AcPRMT1 protein comprised of 352 amino acids with a SAM-dependent
      methyltransferase PRMT-type domain. The expression level of AcPRMT1 was highly
      increased during encystation of A. castellanii. The EGFP-AcPRMT1 fusion protein
      was distributed over the cytoplasm, but it was mainly localized in the nucleus of
      Acanthamoeba. Knock down of AcPRMT1 by synthetic siRNA with a complementary
      sequence failed to form mature cysts. These findings suggested that AcPRMT1 plays
      a critical role in the regulation of encystation of A. castellanii. The target
      gene of AcPRMT1 regulation and the detailed mechanisms need to be investigated by
      further studies.

PMID- 28506030
TI  - Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon alpha
      2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C
      Virus.
AB  - Background/Aims: The present study aimed to evaluate the safety and efficacy of
      simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG
      IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly
      and/or cirrhotic patients, and to elucidate the factors contributing to a
      sustained virologic response (SVR). Methods: One hundred IFN ineligible patients
      infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100
      mg) was given orally together with reduced doses of PEG-IFN-alpha 2a (90 MUg),
      and ribavirin (200 mg less than the recommended dose). Results: The patients'
      median age was 70 years, and 70 patients were cirrhotic. Three patients (3%)
      discontinued treatment due to adverse events. The SVR rate was 64%. Factors that
      significantly contributed to the SVR included the gamma-glutamyl transferase and
      alpha-fetoprotein levels, interleukin- 28B (IL28B) polymorphism status, and the
      level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed
      that the IL28B polymorphism status was the only independent factor that predicted
      the SVR, with a positive predictive value of 77%. Conclusions: Simeprevir-based
      triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective
      for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism
      status was a useful predictor of the SVR.

PMID- 28506032
TI  - DNA Methylation of Gene Expression in Acanthamoeba castellanii Encystation.
AB  - Encystation mediating cyst specific cysteine proteinase (CSCP) of Acanthamoeba
      castellanii is expressed remarkably during encystation. However, the molecular
      mechanism involved in the regulation of CSCP gene expression remains unclear. In
      this study, we focused on epigenetic regulation of gene expression during
      encystation of Acanthamoeba. To evaluate methylation as a potential mechanism
      involved in the regulation of CSCP expression, we first investigated the
      correlation between promoter methylation status of CSCP gene and its expression.
      A 2,878 bp of promoter sequence of CSCP gene was amplified by PCR. Three CpG
      islands (island 1-3) were detected in this sequence using bioinformatics tools.
      Methylation of CpG island in trophozoites and cysts was measured by bisulfite
      sequence PCR. CSCP promoter methylation of CpG island 1 (1,633 bp) was found in
      8.2% of trophozoites and 7.3% of cysts. Methylation of CpG island 2 (625 bp) was
      observed in 4.2% of trophozoites and 5.8% of cysts. Methylation of CpG island 3
      (367 bp) in trophozoites and cysts was both 3.6%. These results suggest that DNA
      methylation system is present in CSCP gene expression of Acanthamoeba. In
      addition, the expression of encystation mediating CSCP is correlated with
      promoter CpG island 1 hypomethylation.

PMID- 28506033
TI  - Differential Protein Expressions in Virus-Infected and Uninfected Trichomonas
      vaginalis.
AB  - Protozoan viruses may influence the function and pathogenicity of the protozoa.
      Trichomonas vaginalis is a parasitic protozoan that could contain a double
      stranded RNA (dsRNA) virus, T. vaginalis virus (TVV). However, there are few
      reports on the properties of the virus. To further determine variations in
      protein expression of T. vaginalis, we detected 2 strains of T. vaginalis; the
      virus-infected (V+) and uninfected (V-) isolates to examine differentially
      expressed proteins upon TVV infection. Using a stable isotope N-terminal labeling
      strategy (iTRAQ) on soluble fractions to analyze proteomes, we identified 293
      proteins, of which 50 were altered in V+ compared with V- isolates. The results
      showed that the expression of 29 proteins was increased, and 21 proteins
      decreased in V+ isolates. These differentially expressed proteins can be
      classified into 4 categories: ribosomal proteins, metabolic enzymes, heat shock
      proteins, and putative uncharacterized proteins. Quantitative PCR was used to
      detect 4 metabolic processes proteins: glycogen phosphorylase, malate
      dehydrogenase, triosephosphate isomerase, and glucose-6-phosphate isomerase,
      which were differentially expressed in V+ and V- isolates. Our findings suggest
      that mRNA levels of these genes were consistent with protein expression levels.
      This study was the first which analyzed protein expression variations upon TVV
      infection. These observations will provide a basis for future studies concerning
      the possible roles of these proteins in host-parasite interactions.

PMID- 28506034
TI  - Occurrence of Cryptosporidium and Giardia and the Relationship between Protozoa
      and Water Quality Indicators in Swimming Pools.
AB  - A total of 60 samples were collected from 35 swimming pools in Beijing, China,
      and the presence of Cryptosporidium and Giardia were investigated. The results
      showed that 16.7% and 15.0% of samples were positive for Cryptosporidium oocyst
      and Giardia cysts, respectively, with a mean concentration of 0.30 oocysts/10 L
      and 0.27 cysts/10 L. The oocysts and cysts were found to have higher rates of
      occurrence in August than in May. Genotyping confirmed the presence of
      Cryptosporidium hominis, C. parvum, and Giardia assemblages A and B, all of which
      were associated with human infections. The predominant species/assemblages were
      C. hominis and Giardia assemblage A. Analyses of the relationships between
      parasite oocysts/cysts, indicator bacteria, and physical-chemical parameters
      revealed that there was no correlation between 2 parasites and fecal bacterial
      indicators, whilst there was a significant correlation between protozoa and urea
      concentration, which indicates that urea concentration rather than fecal
      bacterial indicators might be an appropriate index for chlorine-resistant
      protozoa in swimming pools. This study provides useful information to improve the
      safety of swimming pool water and deduce the risk of protozoan infections.

PMID- 28506035
TI  - Simultaneous Molecular Detection of Cryptosporidium and Cyclospora from Raw
      Vegetables in Korea.
AB  - Cryptosporidium and Cyclospora are well-known coccidian protozoa that can cause
      waterborne and foodborne diarrheal illnesses. There have been a few reports
      regarding contamination in different vegetables with Cryptosporidium, but no data
      are available regarding the sources of Cyclospora infections in Korea. In the
      present study, we collected 6 kinds of vegetables (perilla leaves, winter-grown
      cabbages, chives, sprouts, blueberries, and cherry tomatoes) from July 2014 to
      June 2015, and investigated contamination by these 2 protozoa using multiplex
      quantitative real-time PCR. Among 404 vegetables, Cryptosporidium and Cyclospora
      were detected in 31 (7.7%) and 5 (1.2%) samples, respectively. In addition,
      Cryptosporidium was isolated from all 6 kinds of vegetables, whereas Cyclospora
      was detected in 4 kinds of vegetables (except perilla leaves and chives).
      Cryptosporidium (17.8%) and Cyclospora (2.9%) had the highest detection rates in
      chives and winter-grown cabbages, respectively. Cryptosporidium was detected all
      year long; however, Cyclospora was detected only from October to January. In 2
      samples (sprout and blueberry), both Cryptosporidium and Cyclospora were
      detected. Further investigations using TaqI restriction enzyme fragmentation and
      nested PCR confirmed Cryptosporidium parvum and Cyclospora cayetanensis,
      respectively. In conclusion, we detected C. cayetanensis in vegetables for the
      first time in Korea. This suggests that screening should be employed to prevent
      these protozoal infections in Korea.

PMID- 28506036
TI  - Influenza M1 Virus-Like Particles Consisting of Toxoplasma gondii Rhoptry Protein
      4.
AB  - Toxoplasma gondii infections occur throughout the world, and efforts are needed
      to develop various vaccine candidates expressing recombinant protein antigens. In
      this study, influenza matrix protein (M1) virus-like particles (VLPs) consisting
      of T. gondii rhoptry antigen 4 (ROP4 protein) were generated using baculovirus
      (rBV) expression system. Recombinant ROP4 protein with influenza M1 were cloned
      and expressed in rBV. SF9 insect cells were coinfected with recombinant rBVs
      expressing T. gondii ROP4 and influenza M1. As the results, influenza M1 VLPs
      showed spherical shapes, and T. gondii ROP4 protein exhibited as spikes on VLP
      surface under transmission electron microscopy (TEM). The M1 VLPs resemble
      virions in morphology and size. We found that M1 VLPs reacted with antibody from
      T. gondii-infected mice by western blot and ELISA. This study demonstrated that
      T. gondii ROP4 protein can be expressed on the surface of influenza M1 VLPs and
      the M1 VLPs containing T. gondii ROP4 reacted with T. gondii-infected sera,
      indicating the possibility that M1 VLPs could be used as a coating antigen for
      diagnostic and/or vaccine candidate against T. gondii infection.

PMID- 28506037
TI  - Diversity of vir Genes in Plasmodium vivax from Endemic Regions in the Republic
      of Korea: an Initial Evaluation.
AB  - Variant surface antigens (VSAs) encoded by pir families are considered to be the
      key proteins used by many Plasmodium spp. to escape the host immune system by
      antigenic variation. This attribute of VSAs is a critical issue in the
      development of a novel vaccine. In this regard, a population genetic study of vir
      genes from Plasmodium vivax was performed in the Republic of Korea (ROK). Eighty
      five venous blood samples and 4 of the vir genes, namely vir 27, vir 21, vir 12,
      and vir 4, were selected for study. The number of segregating sites (S), number
      of haplotypes (H), haplotype diversity (Hd), DNA diversity (pi and Thetaw), and
      Tajima's D test value were conducted. Phylogenetic trees of each gene were
      constructed. The vir 21 (S=143, H=22, Hd=0.827) was the most genetically diverse
      gene, and the vir 4 (S=6, H=4, Hd=0.556) was the opposite one. Tajima's D values
      for vir 27 (1.08530, P>0.1), vir 12 (2.89007, P<0.01), and vir 21 (0.40782,
      P>0.1) were positive, and that of vir 4 (-1.32162, P>0.1) was negative. All
      phylogenetic trees showed 2 clades with no particular branching according to the
      geographical differences and cluster. This study is the first survey on the vir
      genes in ROK, providing information on the genetic level. The sample sequences
      from vir 4 showed a clear difference to the Sal-1 reference gene sequence,
      whereas they were very similar to those from Indian isolates.

PMID- 28506038
TI  - PCR-RFLP for Rapid Subtyping of Plasmodium vivax Korean Isolates.
AB  - Vivax malaria reemerged in Korea in 1993 and the outbreak has been continued with
      fluctuating numbers of annual indigenous cases. Understanding the nature of the
      genetic population of Plasmodium vivax circulating in Korea is beneficial for the
      knowledge of the nationwide parasite heterogeneity and in the implementation of
      malaria control programs in the country. Previously, we analyzed polymorphic
      nature of merozoite surface protein-1 (MSP-1) and MSP-3alpha in Korean P. vivax
      population and identified the Korean P. vivax population has been diversifying
      rapidly, with the appearance of parasites with new genetic subtypes, despite the
      recent reduction of the disease incidence. In the present study, we developed
      simple PCR-RFLP methods for rapid subtyping of MSP-1 and MSP-3alpha of Korean P.
      vivax isolates. These PCR-RFLP methods were able to easily distinguish each
      subtype of Korean P. vivax MSP-1 and MSP-3alpha with high accuracy. The PCR-RFLP
      subtyping methods developed here would be easily applied to massive
      epidemiological studies for molecular surveillance to understand genetic
      population of P. vivax and to supervise the genetic variation of the parasite
      circulating in Korea.

PMID- 28506039
TI  - Plasma D-dimer Can Effectively Predict the Prospective Occurrence of Ascites in
      Advanced Schistosomiasis Japonica Patients.
AB  - China still has more than 30,000 patients of advanced schistosomiasis while new
      cases being reported consistently. D-dimer is a fibrin degradation product. As
      ascites being the dominating symptom in advanced schistosomiasis, the present
      study aimed to explore a prediction model of ascites with D-dimer and other
      clinical easy-achievable indicators. A case-control study nested in a prospective
      cohort was conducted in schistosomiasis-endemic area of southern China. A total
      of 291 patients of advanced schistosomiasis were first investigated in 2013 and
      further followed in 2014. Information on clinical history, physical examination,
      and abdominal ultrasonography, including the symptom of ascites was repeatedly
      collected. Result showed 44 patients having ascites. Most of the patients'
      ascites were confined in the kidney area with median area of 20 mm2. The level of
      plasma D-dimer and pertinent liver function indicators were measured at the
      initial investigation in 2013. Compared with those without ascites, cases with
      ascites had significantly higher levels of D-dimer (0.71+/-2.44 MUg/L vs 0.48+/
      2.12 MUg/L, P=0.005), as well ALB (44.5 vs 46.2, g/L) and Type IV collagen (50.04
      vs 44.50 MUg/L). Receiver operating characteristic curve analyses indicated a
      moderate predictive value of D-dimer by its own area under curve (AUC) of 0.64
      (95% CI: 0.54-0.73) and the cutoff value as 0.81 MUg/L. Dichotomized by the
      cutoff level, D-dimer along with other categorical variables generated a
      prediction model with AUC of 0.76 (95% CI: 0.68-0.89). Risks of patients with
      specific characteristics in the prediction model were summarized. Our study
      suggests that the plasma D-dimer level is a reliable predictor for incident
      ascites in advanced schistosomiasis japonica patients.

PMID- 28506040
TI  - Codon Usage Patterns of Tyrosinase Genes in Clonorchis sinensis.
AB  - Codon usage bias (CUB) is a unique property of genomes and has contributed to the
      better understanding of the molecular features and the evolution processes of
      particular gene. In this study, genetic indices associated with CUB, including
      relative synonymous codon usage and effective numbers of codons, as well as the
      nucleotide composition, were investigated in the Clonorchis sinensis tyrosinase
      genes and their platyhelminth orthologs, which play an important role in the
      eggshell formation. The relative synonymous codon usage patterns substantially
      differed among tyrosinase genes examined. In a neutrality analysis, the
      correlation between GC12 and GC3 was statistically significant, and the
      regression line had a relatively gradual slope (0.218). NC-plot, i.e., GC3 vs
      effective number of codons (ENC), showed that most of the tyrosinase genes were
      below the expected curve. The codon adaptation index (CAI) values of the
      platyhelminth tyrosinases had a narrow distribution between 0.685/0.714 and
      0.797/0.837, and were negatively correlated with their ENC. Taken together, these
      results suggested that CUB in the tyrosinase genes seemed to be basically
      governed by selection pressures rather than mutational bias, although the latter
      factor provided an additional force in shaping CUB of the C. sinensis and
      Opisthorchis viverrini genes. It was also apparent that the equilibrium point
      between selection pressure and mutational bias is much more inclined to selection
      pressure in highly expressed C. sinensis genes, than in poorly expressed genes.

PMID- 28506041
TI  - Identification of Tick Species Collected from Wild Boars and Habitats of Wild
      Boars and Domestic Pigs in the Republic of Korea.
AB  - Tick is one of the most important arthropods in the transmission of vector-borne
      diseases. In this study, we investigated the abundance and species of ticks
      associated with swine and their habitats to assess the risk of spread of tick
      borne diseases in host species, such as wild boars. Ticks were collected from 24
      grazing or traditionally reared domestic pig farms and 8 habitats of wild boars
      in 8 provinces and 1 city in the Republic of Korea, by using the dragging and
      flagging methods. Ticks were also collected directly from 49 wild boars by using
      fine forceps. A total of 9,846 hard ticks were collected, including 4,977
      Haemaphysalis longicornis, 4,313 Haemaphysalis flava, 508 Ixodes nipponensis, 1
      Ixodes turdus, and 47 Amblyomma testudinarium. A total of 240 hard ticks were
      collected from 49 wild boars, including 109 H. flava, 84 H. longicornis, and 47
      A. testudinarium. A total of 578 hard ticks were collected from areas around
      domestic pig farms. Only 2 hard tick species, 546 H. longicornis and 32 H. flava,
      were collected from these areas. A total of 9,028 hard ticks were collected from
      wild boars of 8 habitats, including 4,347 H. longicornis, 4,172 H. flava, 508 I.
      nipponensis, and 1 I. turdus. A. testudinarium was collected only from wild
      boars, and I. nipponensis and I. turdus were collected only from the habitats of
      wild boars.

PMID- 28506042
TI  - Life Cycle of Dermacentor everestianus Hirst, 1926 (Acari: Ixodidae) under
      Laboratory Conditions.
AB  - This study investigated the development characteristics of Dermacentor
      everestianus under laboratory conditions. The time taken for D. everestianus to
      complete the whole life cycle was 110.2 days on average, and the average
      developmental durations of larvae and nymphs were 17.1 days and 29.5 days,
      respectively. The summation of the prefeeding, feeding, and preoviposition
      periods of females was 17.8 days, and the oviposition and egg incubation lasted
      for 18.1 days and 27.7 days, respectively. A highly positive correlation was
      observed between the weight of engorged female and the number of egg mass laid
      (r=0.947). The reproductive efficiency index and the reproductive fitness index
      were 7.1 and 6.1, respectively.

PMID- 28506043
TI  - First Paleoparasitological Report on the Animal Feces of Bronze Age Excavated
      from Shahr-e Sukhteh, Iran.
AB  - Shahr-e Sukhteh (meaning burnt city in Persian) in Iran is an archeological site
      dated back to around 3,200-1,800 BC. It is located in Sistan and Baluchistan
      Province of Iran and known as the junction of Bronze Age trade routes crossing
      the Iranian plateau. It was appointed as current study area for
      paleoparasitological investigations. Excavations at this site have revealed
      various archeological materials since 1967. In the present study, sheep and
      carnivore coprolites excavated from this site were analyzed by means of
      rehydration technique using TSP solution for finding helminth eggs. Dicrocoelium
      dendriticum, Capillaria sp., and Taenia sp. eggs were identified, while some
      other objects similar to Anoplocephalidae and Toxocara spp. eggs were also
      retrieved from the samples but their measured parameters did not match those of
      these species. The present paper illustrates the first paleoparasitological
      findings of Bronze Age in eastern Iran supporting the economic activities,
      peopling, and communication as well as the appropriate condition for zoonotic
      helminthiasis life cycle in Shahr-e Sukhteh archeological site.

PMID- 28506044
TI  - Seroprevalence and Risk Factors of Toxoplasma gondii Infection among Cat Sitters
      in Korea.
AB  - The seroprevalence of human toxoplasmosis has been increasing in Korea, and it is
      controversial whether cats are an important infection source or not. This study
      was performed to evaluate the seroprevalence of Toxoplasma gondii infection in a
      high risk group (cat sitters) and to determine the possible importance of cats as
      an infection source in Korea. Risk factors, including the age, sex, and diet of
      cat sitters, their contact experience and contact frequency with stray cats, and
      origin, number, and outdoor activity of their pet cats, were analyzed using
      structured questionnaires. A total of 673 serum samples from people who have
      frequent contact with cats (high risk group) and 1,114 samples from general
      people (low risk group) were examined for specific IgG antibodies against T.
      gondii by ELISA. The results revealed that the overall seroprevalence of T.
      gondii infection was 7.4% (n=1,787). The seroprevalence among low risk group was
      8.0% (89/1,114), whereas that among high risk group was rather lower 6.4%
      (43/673), though this difference was statistically not significant (P=0.211).
      Among the risk factors, only the outdoor activity of pet cats was important;
      people having cats with outdoor activities revealed 2 times higher seroprevalence
      than people having cats with only indoor activities (P=0.027). In conclusion, the
      seroprevalence of T. gondii was not significantly different between the high risk
      group and low risk group, and the importance of cats as a source of infection in
      Korea is questionable.

PMID- 28506047
TI  - First Report of Clavinema mariae (Nematoda: Philometridae) in Cultured Rockfish,
      Sebastes schlegeli, in Cheonsuman (Bay), the Republic of Korea.
AB  - In July 2012, philometrid nematodes were discovered in cultured rockfish
      (Sebastes schlegeli) in Cheonsuman (Bay), the Republic of Korea. The nematodes
      were detected in the epithelial tissues of the rockfish and were identified as
      Clavinema mariae based on morphological studies using light and scanning electron
      microscopy. They revealed the characteristics same as previously identified C.
      mariae, notably having a long body with narrow posterior half, no caudal
      projection, a cylindrical-shaped esophagus, a well-developed anterior bulbous
      part of the esophagus, cephalic papillae, and a dorsal esophageal gland. This is
      the first confirmation of C. mariae infection in rockfish in Korea.

PMID- 28506048
TI  - Indoor Occurrence of the Ghost Ant Tapinoma melanocephalum (Hymenoptera:
      Formicidae) in Urban Homes in Korea.
AB  - The ghost ant Tapinoma melanocephalum is a common household pest worldwide. The
      present study examined the occurrence of the species in urban homes in Korea.
      During the period of September 2014 to January 2016, T. melanocephalum workers
      were collected from 58 homes at 29 different localities using bait traps with 10%
      sugar solution. The species was widely distributed throughout urban homes at 29
      different localities, and the indoor occurrence of T. melanocephalum was highest
      in Seoul (32.7%) and metropolitan areas of Gyeonggi-do (Province) (29.3%). The
      indoor incidence rate of T. melanocephalum peaked in September (22.8%), remained
      moderate from October through April, and peaked again in May (15.7%). In
      contrast, a low incidence was observed from June to August (7.0%). The present
      study provides evidence that native ants, such as T. melanocephalum, are
      potential indoor pests of homes in Korea throughout the year.

PMID- 28506045
TI  - Serological and Molecular Detection of Toxoplasma gondii and Babesia microti in
      the Blood of Rescued Wild Animals in Gangwon-do (Province), Korea.
AB  - Infections of Toxoplasma gondii and Babesia microti are reported in many wild
      animals worldwide, but information on their incidence and molecular detection in
      Korean wild fields is limited. In this study, the prevalence of T. gondii and B.
      microti infection in blood samples of 5 animal species (37 Chinese water deer, 23
      raccoon dogs, 6 roe deer, 1 wild boar, and 3 Eurasian badgers) was examined
      during 2008-2009 in Gangwon-do (Province), the Republic of Korea (=Korea) by
      using serological and molecular tests. The overall seropositivity of T. gondii
      was 8.6% (6/70); 10.8% in Chinese water deer, 4.3% in raccoon dogs, and 16.7% in
      roe deer. PCR revealed only 1 case of T. gondii infection in Chinese water deer,
      and phylogenic analysis showed that the positive isolate was practically
      identical to the highly pathogenetic strain type I. In B. microti PCR, the
      positive rate was 5.7% (4/70), including 2 Chinese water deer and 2 Eurasian
      badgers. Phylogenetic analysis results of 18S rRNA and the beta-tubulin gene
      showed that all positive isolates were US-type B. microti. To our knowledge, this
      is the first report of B. microti detected in Chinese water deer and Eurasian
      badger from Korea. These results indicate a potentially high prevalence of T.
      gondii and B. microti in wild animals of Gangwon-do, Korea. Furthermore, Chinese
      water deer might act as a reservoir for parasite infections of domestic animals.

PMID- 28506046
TI  - Interaction between Trichomonas vaginalis and the Prostate Epithelium.
AB  - Most men infected with Trichomonas vaginalis are asymptomatic and can remain
      undiagnosed and untreated. This has been hypothesized to result in chronic
      persistent prostatic infection. Adhesion of the protozoan organisms to mucosal
      cells is considered a first and prerequisite step for T. vaginalis infection.
      Adhesion of T. vaginalis to prostate epithelial cells has not yet been observed;
      however, there are several reports about inflammation of prostate epithelial
      cells induced by T. vaginalis. The aim of this study was to investigate whether
      adhesion and cytotoxicity of T. vaginalis are involved in inflammation of
      prostate epithelial cells. When RWPE-1 cells were infected with T. vaginalis
      (1:0.4 or 1:4), adhesion of T. vaginalis continuously increased for 24 hr or 3
      hr, respectively. The cytotoxicity of prostate epithelial cells infected with T.
      vaginalis (RWPE-1: T. vaginalis=1:0.4) increased at 9 hr; at an infection ratio
      of 1:4, cytotoxicity increased after 3 hr. When the RWPE-1 to T. vaginalis ratio
      was 1:0.4 or 1:4, production of IL-1beta, IL-6, CCL2, and CXCL8 also increased.
      Epithelial-mesenchymal transition (EMT) was verified by measuring decreased E
      cadherin and increased vimentin expression at 24 hr and 48 hr. Taken together,
      the results indicate that T. vaginalis adhered to prostate epithelial cells,
      causing cytotoxicity, pro-inflammatory cytokine production, and EMT. Our findings
      suggest for the first time that T. vaginalis may induce inflammation via adhesion
      to normal prostate epithelial cells.

PMID- 28506049
TI  - [Laparoscopic Non-Ischemic Partial Nephrectomy Using a Microwave Tissue
      Coagulator : A Single-Institutional Study].
AB  - We retrospectively investigated the surgical outcomes of renal cell carcinoma
      (RCC), perioperative complications, and residual renal function in patients
      receiving laparoscopic non-ischemic partial nephrectomy using a microwave tissue
      coagulator (MTC). Between January 2002 and December 2015, laparoscopic non
      ischemic partial nephrectomy using MTC was performed in 49 patients. The
      histological diagnosis was RCC in 38 patients, angiomyolipoma in 4, oncocytoma in
      2, and others in 5. A histologicallyproven positive surgical margin was observed
      in 1 (2.0%). Postoperative urine leakage occurred in 1, and it was treated
      conservatively. The mean follow-up period was 32.0 months. Although there was no
      patient who died of RCC, local recurrence occurred in 2 patients (4.1%) during
      the follow-up period. One of these 2 patients had a positive surgical margin.
      Deterioration of the residual renal function was not observed. Laparoscopic non
      ischemic partial nephrectomy using MTC was safe and useful in terms of cancer
      control and preservation of renal function.

PMID- 28506050
TI  - [A Clinicopathologic Study of 6 Patients with Histologically Pure Seminoma But
      Elevated Serum Alpha-Fetoprotein].
AB  - Histologically pure seminoma with elevated alpha-fetoprotein (AFP), so-called AFP
      positive seminoma, is rare. It is recommended that patients with AFP-positive
      seminoma be managed as non-seminoma, but the clinical features and prognosis of
      this disease are not fully understood. In this study, we retrospectively analyzed
      6 cases of metastatic AFP-positive seminoma at Tsukuba University Hospital (TUH).
      AFP was elevated before induction chemotherapy in 4 patients with an average of
      1,372 ng/ml. In the remaining 2 patients, AFP became elevated during or after
      induction chemotherapy. In all 4 patients examined, AFPL3% was abnormally
      increased. As induction chemotherapy, all patients received bleomycin, etoposide
      and cisplatin (BEP), which was then followed by etoposide, ifosfamide and
      cisplatin (VIP) in 3 patients. After or during induction chemotherapy, 3 patients
      suffered from disease progression accompanied by AFP elevation. All 3 were
      treated by salvage chemotherapy and surgery. Four patients underwent
      retroperitoneal lymph node dissection (RPLND) after induction chemotherapy ; the
      pathological findings were necrosis in 3 patients, and viable nonseminomatous
      cancer in 1 patient. Furthermore, RPLND was performed as salvage surgery in 3
      patients ; the pathological findings were necrosis, viable nonseminomatous cancer
      and teratoma with malignant transformation, respectively. The 5-year progression
      free survival rate of the 6 patients was 50%, which is somewhat inferior to that
      of poor-prognosis non-seminoma patients treated at TUH. One patient ultimately
      died of cancer, and the remaining 5 are in remission with a median follow-up of
      58 months. The present study demonstrates that AFP-positive seminoma patients
      have a higher risk of relapse compared to non-seminoma patients.

PMID- 28506051
TI  - [A Case of Thyroid-Like Follicular Carcinoma of the Kidney].
AB  - A 51-year-oldwoman with a right renal mass was referredto our hospital.
      Computedtomographic (CT) scan demonstrated a 30 mm-diameter renal mass with
      delayed enhancement. She underwent a robotassistedlaparoscopic right partial
      nephrectomy. The pathological examination showedthat tumor cells with
      eosinophilic, clear cytoplasm formedtubules of various sizes containing colloid
      like material, which resembled the findings of thyroidfollicular carcinoma. The
      tumor was immunoreactive for vimentin andcytokeratin (CK) 7, whereas it
      lackedreactivity for thyroidtranscription factor-1 (TTF-1) or thyroglobulin. No
      tumors were detectedin the thyroidglandor other organs of the patient.
      Subsequently, the diagnosis of thyroidlike follicular carcinoma of the kidney
      (TLFCK) was determined. At 4 months postoperatively, the patient is alive with no
      evidence of disease recurrence. TLFCK is an extremely rare subtype of renal
      cancer, and only 26 cases have been reportedpreviously. We provide a brief
      literature review on this cancer.

PMID- 28506052
TI  - [Renal Cell Carcinoma with Retroperitoneal Metastases and Renal Invasion from
      Breast Cancer : A Case Report].
AB  - A 67-year-old female was hospitalized with back pain. Computed tomography (CT)
      incidentally revealed a tumor in her left kidney tumor (33 mm) and bilateral
      breast tumors. She underwent a breast biopsy and was diagnosed with breast cancer
      (invasive lobular cancer, cT2N0M0). The renal tumor was suspected to be clear
      cell carcinoma, cT1aN0M0, based on contrast-enhanced CT. Surgery was considered
      necessary for both the breast cancer and renal tumor. First, laparoscopic radical
      nephrectomy was performed for the renal tumor. However, the lateroconal fascia
      adhered strongly to the perirenal fat, and so simple nephrectomy was carried out
      after conversion to open surgery. The perirenal fat was also excised after the
      nephrectomy. A histopathological examination revealed clear cell carcinoma and
      renal invasion by invasive lobular cancer cells. Also, scattered metastases were
      detected in the perirenal fat and the lateroconal fascia. So, it was considered
      that retroperitoneal metastases from the breast cancer had directly invaded the
      kidney. After the operation, the patient received hormonal therapy for her breast
      cancer, and she was still alive and symptom-free 5 months after the operation.

PMID- 28506053
TI  - [Laparoscopic Pyelolithotomy in a Horseshoe Kidney : A Case Report and Review of
      the Literature].
AB  - A 76-year-old man was introduced to our department with a right kidney stone. On
      the basis of further examination, he was diagnosed with a 23 mm right kidney
      stone accompanied with a horseshoe kidney. Retrograde pyelography and diuretic
      renogram revealed a non-obstructed right ureteropelvic junction. Finally, we
      chose laparoscopic pyelolithotomy via peritoneal approach because the stone was
      large and accompanied with a horseshoe kidney. The surgery took 165 minutes and
      the estimated blood loss was 25 ml. There were no minor or major complications.
      Because horseshoe kidney has anatomical abnormalities, it seems to be necessary
      to consider a different treatment strategy from that of an upper urinary tract
      stone in a healthy kidney. We assume that laparoscopic pyelolithotomy is an
      effective and safe procedure for renal pelvic stones in the case of a horseshoe
      kidney.

PMID- 28506054
TI  - [Penile Tuberculosis : A Case Report].
AB  - A 66-year-old man presented with a chief complaint of glans penis pain,
      induration, and discharge of pus. He was prescribed a course of antibiotics, but
      the condition persisted despite treatment. Thus, we differrentially diagnosed the
      patient with penile tuberculosis and pyoderma gangrenosum, and performed a biopsy
      of the penis. The biopsy result was thickening of the horny layer epidermis with
      only a foreign body granuloma composed of inflammatory cells, and did not lead to
      a definitive diagnosis. Thoraca-abdominal computed tomography revealed axillary
      lymphadenopathy with necrosis. Suspecting tuberculosis lymphadenitis, we
      performed T-spot and QuantiFERONtests. The result was T-spot negative and
      QuantiFERONpositive, so we diagnosed the patient with penile tuberculosis, and
      started antituberculosis medication. In about half a year after the start of
      treatment the symptoms subsided, and lymphadenopathy showed reduction.

PMID- 28506057
TI  - Liquid Spray Dielectric Barrier Discharge Induced Plasma-Chemical Vapor
      Generation for the Determination of Lead by ICPMS.
AB  - In the present study, a novel and sensitive liquid spray dielectric barrier
      discharge induced plasma-chemical vapor generation technique (LSDBD-CVG) is
      developed for the determination of lead concentration by inductively coupled
      plasma mass spectrometry (ICPMS). The dissolved Pb2+ is readily converted to
      volatile species by LSDBD plasma induced chemical processes in the presence of 5%
      (v/v) formic acid in a supporting electrolyte (HCl, 0.01 mol L-1). In this LSDBD
      approach, the sample solution is converted to aerosol and simultaneously mixed
      with the DBD plasma generated at the nozzle of a pneumatic nebulizer, which
      greatly facilitates Pb vapor generation because of the enhanced interaction of
      sprayed analytes and the plasma. Optimal conditions for LSDBD-CVG were
      identified, and the interference effects from other metal ions were assessed.
      Under optimized conditions, the detection limit of Pb was found to be 0.003 MUg L
      1. The repeatability, expressed as the relative standard deviation (RSD) of the
      peak height, for the five replicate measurements of 0.03 and 1 MUg L-1 lead
      standard, were 2.1% and 1.7%, respectively. Compared with other vapor generation
      methods, this new LSDBD-CVG offers several advantages including no requirement of
      unstable reagents, fast response, and easy coupling with flow injection, along
      with high tolerance for coexisting ions. The accuracy of the proposed method is
      demonstrated by successful analysis of Pb in reference material of stream
      sediment (GBW07311), soil (GBW07403), basalt (BCR-2), and simulated water sample
      (GBW08601). The proposed LSDBD-CVG extends the scope of elements accessible by
      plasma-CVG and provides an alternative efficient green approach for the vapor
      generation of Pb.

PMID- 28506055
TI  - Clinical features and outcomes of patients with hepatocellular carcinoma
      complicated with bile duct invasion.
AB  - BACKGROUND/AIMS: Little is known about the treatment or outcomes of
      hepatocellular carcinoma (HCC) complicated with bile duct invasion. METHODS: A
      total of 247 consecutive HCC patients with bile duct invasion at initial
      diagnosis were retrospectively included. RESULTS: The majority of patients had
      Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor
      thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months.
      Various modalities of treatment were initially employed including surgical
      resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and
      conservative management (42.9%). Among the patients with obstructive jaundice
      (n=88), successful biliary drainage was associated with better overall survival
      rate. Among the patients with BCLC stage C, overall survival differed depending
      on the initial treatment for HCC; surgical resection, TACE, systemic
      chemotherapy, and conservative management showed overall survival rates of 11.5,
      6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical
      resection and repeated TACE were significant prognostic factors for HCC patients
      with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively).
      CONCLUSIONS: The survival of HCC patients with bile duct invasion at initial
      diagnosis is generally poor. However, aggressive treatments for HCC such as
      resection or biliary drainage may be beneficial therapeutic options for patients
      with preserved liver function.

PMID- 28506058
TI  - Differential Protein Analysis of IPEC-J2 Cells Infected with Porcine Epidemic
      Diarrhea Virus Pandemic and Classical Strains Elucidates the Pathogenesis of
      Infection.
AB  - Porcine epidemic diarrhea (PED) re-emerged in China in late 2010 and has now
      become widespread. Accumulated evidence indicates that this large-scale outbreak
      of diarrhea was caused by variants of the highly virulent porcine epidemic
      diarrhea virus (PEDV). A pandemic PEDV YC2014 strain (YC2014) was isolated from
      clinical samples. An iTRAQ-based comparative quantitative proteomic study of IPEC
      J2 cells infected with YC2014 and a classical CV777 strain (CV777) was performed
      to determine the differences between pandemic and classical PEDV strain
      infection. Totals of 353 and 299 differentially expressed proteins were
      identified upon YC2014 and CV777 infection, respectively. The canonical pathways
      and functional networks involved in both PEDV infections were analyzed. The
      results indicated that the PEDV suppressed protein synthesis of IPEC-J2 cells
      through down-regulation of the PI3K-AKT/mTOR signaling pathways. Infection with
      YC2014 could activate the JAK-STAT signaling pathway and the NF-kappaB pathway
      more intensively than CV777. YC2014 could activate NF-kappaB pathway more
      intensively than CV777. On the basis of differentially expressed proteins, we
      propose that PEDV might disrupt apoptosis and may elicit stronger inflammatory
      cascades as well. This study might contribute to an understanding of the
      pathogenesis of PEDV infection and aid in the development of effective preventive
      and control vaccines.

PMID- 28506056
TI  - Risk score model for the development of hepatocellular carcinoma in treatment
      naive patients receiving oral antiviral treatment for chronic hepatitis B.
AB  - BACKGROUND/AIMS: This study aimed to develop and validate a risk prediction model
      for the development of hepatocellular carcinoma (HCC) in treatment-naive patients
      receiving oral antiviral treatment for chronic hepatitis B (CHB). METHODS: We
      investigated 2,061 Korean treatment-naive patients with CHB treated with
      entecavir as an initial therapy. A risk score model for HCC development was
      developed based on multivariable Cox regression model in a single center (n=990)
      and was validated using the time-dependent area under the receiver operating
      characteristic curve (AUROC) in three other centers (n=1,071). The difference of
      HCC development among risk groups (low, intermediate, and high) categorized by
      risk score was also investigated. RESULTS: The cumulative incidence rates of HCC
      at 5 years were 11.2% and 8.9% in the testing and validation cohorts,
      respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC
      RESCUE) is formulated as (age+15*gender [female=0 / male=1]+23*cirrhosis
      [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82,
      0.81, and 0.81, respectively, in the validation cohort. A significant difference
      of HCC development in each risk group was determined by the 5-year HCC risk score
      in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%;
      high risk group, 41.2%, p<0.001). CONCLUSIONS: The study presents a new risk
      score model with a good ability to predict HCC development and determine high
      risk patients for HCC development consisting of readily available clinical
      factors in treatment-naive CHB patients receiving entecavir.

PMID- 28506060
TI  - Remobilization Dynamics of Caffeine, Ciprofloxacin, and Propranolol following
      Evaporation-Induced Immobilization in Porous Media.
AB  - Changing weather conditions can cause cycles of wetting and drying in the
      unsaturated zone. When porewater evaporates, any nonvolatile solutes present in
      the pores will be driven to adsorb and ultimately precipitate on solid surfaces.
      When media are subsequently resaturated through rainfall infiltration, the
      remobilization of solutes likely depends on both the hydraulics of resaturation
      and the dynamics of dissolution processes. The focus of this work was to study
      the dynamics of remobilization of three different emerging contaminants
      (caffeine, ciprofloxacin, and propranolol) and two model compounds (fluorescein
      and sulforhodamine B) from porous media following evaporation of porewater.
      Remobilization column experiments were conducted to study this phenomenon and
      were evaluated using a finite difference model developed to simulate the
      adsorption-desorption dynamics during resaturation and elution. Results indicate
      that dissolution dynamics become increasingly important with increasing
      adsorption affinity for solid surfaces. Trends in observed elution behavior are
      not well-predicted from chemical properties, such as solubility. One of the most
      significant observations of the work is the presence of spikes in elution
      concentrations well above initial porewater concentration, resulting from the
      hydraulics of the resaturation process. The effect is most significant in highly
      mobile compounds that exhibit low adsorption affinity for solid surfaces.

PMID- 28506061
TI  - An Elastic Hydrogen-Bonded Cross-Linked Organic Framework for Effective Iodine
      Capture in Water.
AB  - A crystalline microporous hydrogen-bonded cross-linked organic framework has been
      developed through covalent photo-cross-linking of molecular monomers that are
      assembled in a crystalline state. The elastic framework expands its void space to
      adsorb iodine rapidly with a high uptake capacity in an aqueous environment as
      well as recovering its crystalline form after the release of iodine.

PMID- 28506062
TI  - LC-MS Untargeted Metabolomics To Explain the Signal Metabolites Inducing Browning
      in Fresh-Cut Lettuce.
AB  - Enzymatic browning is one of the main causes of quality loss in lettuce as a
      prepared and ready-to-eat cut salad. An untargeted metabolomics approach using
      UPLC-ESI-QTOF-MS was performed to explain the wound response of lettuce after
      cutting and to identify the metabolites responsible of browning. Two cultivars of
      Romaine lettuce with different browning susceptibilities were studied at short
      time intervals after cutting. From the total 5975 entities obtained from the raw
      data after alignment, filtration reduced the number of features to 2959, and the
      statistical analysis found that only 1132 entities were significantly different.
      Principal component analysis (PCA) clearly showed that these samples grouped
      according to cultivar and time after cutting. From those, only 15 metabolites
      belonging to lysophospholipids, oxylipin/jasmonate metabolites, and phenolic
      compounds were able to explain the browning process. These selected metabolites
      showed different trends after cutting; some decreased rapidly, others increased
      but decreased thereafter, whereas others increased during the whole period of
      storage. In general, the fast-browning cultivar showed a faster wound response
      and a higher raw intensity of some key metabolites than the slow-browning one.
      Just after cutting, the fast-browning cultivar contained 11 of the 15 browning
      associated metabolites, whereas the slow-browning cultivar only had 5 of them.
      These metabolites could be used as biomarkers in breeding programs for the
      selection of lettuce cultivars with lower browning potential for fresh-cut
      applications.

PMID- 28506059
TI  - Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine
      Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel
      Biomarker Approach for Assessing Recent Intakes?
AB  - Although the use of low-calorie sweeteners (LCSs) is widespread, methods of
      assessing consumption within free-living populations have inherent limitations.
      Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose,
      cyclamate, and steviol glycosides, are excreted via the urine, and therefore a
      urinary biomarker approach may provide more objective LCS intake data. A LC-ESI
      MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose,
      cyclamate, and the excretory metabolite of steviol glycosides, steviol
      glucuronide, in human urine was developed and validated. Linearity was observed
      over a concentration range of 10-1000 ng/mL with coefficients of determination
      ranging from 0.9969 to 0.9997. Accuracy ranged from 92 to 104%, and intrabatch
      and interday precisions were within acceptable limits with %CV below 8% for all
      compounds. A double-blind, randomized crossover dose-response study was conducted
      to assess the usefulness of urinary LCS excretions (from both fasting spot and a
      full 24-h urine collection) for investigating recent intakes. Both modes of
      sampling were useful for distinguishing between the three short-term intakes of
      acesulfame-K, saccharin, cyclamates, and steviol glycosides (p < 0.001), whereas
      for sucralose, urinary concentrations were useful for distinguishing between low
      (0.1% ADI) and high doses (10% ADI) only (p < 0.001). In summary, this biomarker
      approach may be useful for assessing intakes of five commonly consumed LCSs.

PMID- 28506064
TI  - Ice-Melting Dynamics: The Role of Protons and Interfacial Geometry.
AB  - The surface of ice plays a significant role in melting. To better understand the
      role of the surface, we studied the melting of ice using infrared imaging and pH
      sensitive dyes. Ice was allowed to melt in baths of water of varying depths. When
      the ice melted in a high level of room-temperature water, equal to the height of
      the ice, the conventional melting pattern appeared. When the ice melted in a
      chamber with a lower water level, the melting pattern was unexpected. Seconds
      after the ice was placed in the water, localized regions of low-temperature water
      appeared around the perimeter of the ice. These regions grew radially outward and
      seemed to originate as streams coming from inside the ice. Those streams
      contained high concentrations of protons, as indicated by the color change of a
      pH-sensitive dye initially placed in the water surrounding the ice. This
      observation, together with the temperature distribution and ice-shape changes
      during melting implied that the streams may be propelled by protons from inside
      the ice. In contrast to conventional melting, which progresses from the outer
      surface inward, the stream-melting pattern implies a melting process originating
      inside the ice.

PMID- 28506063
TI  - Extensive Transformation of the Pharmaceutical Carbamazepine Following Uptake
      into Intact Tomato Plants.
AB  - Carbamazepine (CBZ) is an antiepileptic drug which is persistent in wastewater
      treatment plants and the environment. It has been frequently detected in plant
      material after irrigation with treated wastewater. To date, little information
      is, however, available on the transformation of CBZ in plants. In the present
      study, the uptake, translocation, and transformation of CBZ was studied in
      hydroponically grown tomato plants. After 35 days of exposure >80% of the total
      spiked amount of CBZ was taken by the tomato plants and mainly stored in the
      leaves. A total of 11 transformation products (TP) (mainly phase-I) were
      quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and their
      total amount corresponded to 33% of the CBZ taken up. The ratio of CBZ
      metabolites to CBZ was highest in fruits (up to 2.5) and leaves (0.5), suggesting
      an intensive transformation of CBZ in these compartments. Further 10 TPs (phase-I
      and II) were identified by LC-high resolution mass spectrometry screening, likely
      comprising another 12% of CBZ. On the basis of these experiments and on an
      experiment with CBZ-10,11-epoxide a transformation pathway of CBZ in intact
      tomato plants is proposed that involves epoxidation, hydrolysis, hydroxylation,
      ring contraction, or loss of the carbamoyl group, followed by conjugation to
      glucose or cysteine, but also reduction of CBZ. This transformation pathway and
      analytical data of CBZ transformation products allow for their determination also
      in field grown vegetable and for the generation of more accurate exposure data of
      consumers of vegetable irrigated with treated municipal wastewater.

PMID- 28506065
TI  - Opening of an Accessible Microporosity in an Otherwise Nonporous Metal-Organic
      Framework by Polymeric Guests.
AB  - The development of highly porous metal-organic frameworks (MOFs) is greatly
      sought after, due to their wide range of applications. As an alternative to the
      development of new structures, we propose to obtain new stable configurations for
      flexible MOFs by insertion of polymeric guests. The guests prevent the otherwise
      spontaneous closing of the host frameworks and result in stable opened forms.
      Introduced at a fraction of the maximal capacity, polymer chains cause an opening
      of the occupied nanochannels, and because of the MOF reticular stiffness, this
      opening is propagated to the neighboring nanochannels that become accessible for
      adsorption. Composites were obtained by in situ polymerization of vinyl monomers
      in the nanochannels of an otherwise nonporous MOF, resulting in homogeneously
      loaded materials with a significant increase of porosity (SBET = 920 m2/g). In
      addition, by limiting the accessible configurations for the framework and
      forbidding the formation of a reactive intermediate, the polymeric guest
      prevented the thermal degradation of the host MOF even at very low loading (as
      low as 3 wt %) and increased its stability domain by more than 200  degrees C.

PMID- 28506066
TI  - De Novo Computational Design for Development of a Peptide Ligand Oriented to
      VEGFR-3 with High Affinity and Long Circulation.
AB  - The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer
      and has been regarded as a rational target for specific drug delivery. Here,
      VEGFR-3 homing peptide library was efficiently established by computational
      design. Strong fluorescent signals of selected peptides were observed in A549
      cells, but much weaker in other cells. The positive immunostaining overlapped
      with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7).
      In addition, cell uptake of FITC-CP-7 peptide was significantly blocked by
      coinjection of excess CP-7 peptide. After labeled with 131I, the profile of
      pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled
      CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a
      specific uptake of 18.04 +/- 2.04% ID/g at 0.5 h after injection to high VEGFR-3
      expressing A549 tumor mice. More importantly, lower uptake concentration in heart
      (1.06 +/- 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The
      high uptake in the kidneys revealed that renal clearance was the main route of
      131I-CP-7 peptide elimination from the body. Lower accumulation of 131I-CP-7
      peptide in VEGFR-3 negative HeLa tumor mice further indicated that CP-7 peptide
      exhibited a higher tumor-homing efficiency. These studies provided a
      straightforward analytical access to design and screen bioactive peptide based on
      protein structure and revealed that CP-7 peptide represented a promising homing
      peptide of VEGFR-3-positive cancer in vitro and in vivo which could be used as a
      novel target molecule to achieve efficient drug delivery.

PMID- 28506067
TI  - PPh3 Mediated Reductive Annulation Reaction between Isatins and Electron
      Deficient Dienes to Construct Spirooxindole Compounds.
AB  - A PPh3 mediated reductive annulation reaction between isatins and 4,4-dicyano-2
      methylenebut-3-enoates was developed. The reaction provided an alternative method
      for constructing five- and three-membered all-carbon spirooxindole compounds.
      Lithium chloride as a Lewis acid played a key role in the synthesis of
      spirocyclopentenyl oxindole compounds.

PMID- 28506068
TI  - Viologen-Based Conjugated Covalent Organic Networks via Zincke Reaction.
AB  - Morphology influences the functionality of covalent organic networks and
      determines potential applications. Here, we report for the first time the use of
      Zincke reaction to fabricate, under either solvothermal or microwave conditions,
      a viologen-linked covalent organic network in the form of hollow particles or
      nanosheets. The synthesized materials are stable in acidic, neutral, and basic
      aqueous solutions. Under basic conditions, the neutral network assumes radical
      cationic character without decomposing or changing structure. Solvent polarity
      and heating method determine product morphology. Depending upon solvent polarity,
      the resulting polymeric network forms either uniform self-templated hollow
      spheres (HS) or hollow tubes (HT). The spheres develop via an inside-out Ostwald
      ripening mechanism. Interestingly, microwave conditions and certain solvent
      polarities result in the formation of a robust covalent organic gel framework
      (COGF) that is organized in nanosheets stacked several layers thick. In the gel
      phase, the nanosheets are crystalline and form honeycomb lattices. The use of the
      Zincke reaction has previously been limited to the synthesis of small viologen
      molecules and conjugated viologen oligomers. Its application here expands the
      repertoire of tools for the fabrication of covalent organic networks (which are
      usually prepared by dynamic covalent chemistry) and for the synthesis of viologen
      based materials. All three materials-HT, HS, and COGF-serve as efficient
      adsorbents of iodine due to the presence of the cationic viologen linker and, in
      the cases of HT and HS, permanent porosity.

PMID- 28506069
TI  - Interplay between adsorbed peptide structure, trapped water, and surface
      hydrophobicity.
AB  - Atomistic molecular dynamics simulations were used to study the influence of
      interfacial water on the orientation and conformation of a facewise amphipathic
      alpha-helical peptide adsorbed to hydrophilic and hydrophobic substrates. Water
      behavior beneath the peptide adsorbed to a hydrophilic surface was observed to
      vary with the height of the peptide above the surface. In general, the
      orientation of water close to the peptide (with the oxygen atom pointing up
      toward the peptide) was complementary to that observed near the hydrophilic
      surface in the absence of peptide. That is, no change in orientation of water
      trapped between the peptide and a hydrophilic surface is required as the peptide
      approaches the surface. The adsorption of the peptide to the hydrophilic surface
      was observed to be mediated by a layer of ordered water. Water was found to be
      largely excluded on adsorption to the hydrophobic surface. However, the small
      amount of water present was observed to be highly ordered. At the closest point
      of contact to the hydrophobic surface, the peptide was observed to make direct
      contact. These findings shed light on the fundamental driving forces of peptide
      adsorption to hydrophobic and hydrophilic surfaces in aqueous environments.

PMID- 28506070
TI  - Hepatic hematoma after ERCP: two new case reports.
AB  - ERCP is an endoscopic procedure with a complication risk ranging from 2.5 to 8%.
      The most frequent complications are pancreatitis, cholangitis, hemorrhage or
      perforation. Hepatic hematoma after ERCP is a potentially serious, rare
      complication. Not many cases are reported in the literature. We present here two
      new cases of hepatic hematoma following ERCP along with a review of the
      literature and possible therapeutic options.

PMID- 28506071
TI  - Fecal microbiota transplantation in recurrent Clostridium difficile infection in
      a patient with concomitant inflammatory bowel disease.
AB  - The use of fecal microbiota transplantation in recurrent Clostridium difficile
      infection and coexistent inflammatory bowel disease remains unclear. A 61-year
      old man with ulcerative pancolitis was diagnosed with a third recurrence of
      Clostridium difficile infection, previously treated with metronidazole,
      vancomycin and fidaxomicin. Fecal microbiota transplantation of an unrelated
      healthy donor was performed by the lower route. After a twelve month follow-up,
      the patient remains asymptomatic without Clostridium difficile infection relapses
      or inflammatory bowel disease flare-ups. Fecal microbiota transplantation is
      relatively simple to perform, well-tolerated, safe and effective in recurrent
      Clostridium difficile infection with ulcerative pancolitis, as an alternative in
      case of antibiotic therapy failure.

PMID- 28506074
TI  - Primary peripancreatic lymph node tuberculosis as a differential diagnosis of
      pancreatic neoplasia.
AB  - Primary peripancreatic lymph node tuberculosis is an exceptional entity in
      immunocompetent patients, but its incidence is increasing in developed countries
      in recent years due to increasing immigration. It usually presents as a
      pancreatic mass and is misdiagnosed as pancreatic neoplasia in most cases, with
      the diagnosis of tuberculosis occurring after surgery. We report the case of a 38
      year old Pakistani man with abdominal pain of several months duration, who was
      initially diagnosed with a pancreatic neoplasm after detecting a mass in the
      pancreatic isthmus by computed tomography (CT) and abdominal magnetic resonance
      imaging (MRI). However, after performing an endoscopic ultrasound-guided fine
      needle aspiration biopsy (EUS-FNAB), the patient was diagnosed with
      peripancreatic lymph node tuberculosis. After receiving anti-tuberculous
      treatment, the patient presented clinical improvement, despite a small reduction
      in the lesion size. In conclusion, peripancreatic lymph node tuberculosis is part
      of the differential diagnosis of pancreatic neoplasia. Endoscopic ultrasound
      guided fine-needle aspiration biopsy (EUS-FNAB) represents a valuable and useful
      diagnostic tool for detecting this pathology, avoiding surgeries with a high
      morbidity and mortality.

PMID- 28506075
TI  - Cardiovascular Effects of Continuous Positive Airway Pressure Treatment in
      Patients With Obstructive Sleep Apnea: A Meta-Analysis.
AB  - Continuous positive airway pressure (CPAP) is the first-line treatment of
      obstructive sleep apnea (OSA). Obstructive sleep apnea is a predictor of
      cardiovascular (CV) events. In this meta-analysis, we evaluated the effect of
      CPAP on left ventricular ejection fraction (LVEF), CV events, CV mortality, and
      all-cause mortality in patients with OSA. Nine articles (n = 9610 patients) were
      analyzed. Four different meta-analyses were performed: evaluation of LVEF,
      assessment of all-cause mortality, CV mortality, and CV events. Continuous
      positive airway pressure treatment was associated with a significant increase in
      LVEF (mean difference: 2.1%, 95% confidence interval [CI]: 0.8%-3.4%). There was
      a nonsignificant reduction in all-cause mortality (hazard ratio [HR]: 0.92, 95%
      CI: 0.73-1.15) but a significant reduction of 66% in the risk of CV mortality
      associated with the CPAP treatment (HR: 0.34, 95% CI: 0.17-0.68, P = .002). There
      was a nonsignificant reduction in the risk of CV events in the CPAP-treated
      patients (HR: 0.84, 95% CI: 0.60-1.18, P = .31). Our meta-analyses showed that
      CPAP treatment improves LVEF and could have a beneficial effect on CV mortality.

PMID- 28506076
TI  - NOS2 as an Emergent Player in Progression of Cancer.
AB  - Although the inducible form of nitric oxide synthase (NOS2) was initially shown
      to be a major player as an antitumor component of the immune response, more
      recent data have shown that NOS2 expression in cancer cells often predicts poor
      outcome. Unlike growth factors associated with a single oncogenic pathway, nitric
      oxide (NO) has a ubiquitous nature wherein it simultaneously mediates major
      oncogenic pathways from Akt/PI3K and RAS/ERK to HIF1a and TGFb. These interactive
      loops perpetuate oncogenic mechanism that leads to increased cancer stemness,
      proliferation metastasis, chemoresistance, angiogenesis, and immunosuppression.
      Examination of a wide variety of patient tumors demonstrates that NOS2 expression
      is >50% for most cancers. In many cases, elevated NOS2 has been shown to predict
      poor outcome in cancer such as ER- breast cancer, glioma, melanoma, cervical,
      liver, ovarian, and pancreatic. Taken together, NOS2 may be one of the most
      powerful biomarker and predictors of poor prognosis and an ideal target for
      cancer therapy. Antioxid. Redox Signal. 26, 963-965.

PMID- 28506078
TI  - 'My husband is possessed by a jinn': a case study in transcultural mental health.
AB  - Objectives The objective of this study was to discuss jinn possession in Muslim
      culture, and the importance of understanding cultural differences in mental
      health. Conclusion It is important to understand cultural and religious
      differences in psychiatry, as it affects the way patients perceive and attribute
      symptoms. It also helps clinicians to reach an accurate diagnosis and provide
      appropriate treatments. Beliefs about jinn possession should not automatically be
      regarded as delusional. In alleged cases of jinn possession, clinicians should
      consider all the biopsychosocial, cultural and spiritual factors that are unique
      to the individual. Further research is still needed in this area.

PMID- 28506077
TI  - Successful clozapine re-challenge following myocarditis.
AB  - OBJECTIVE: To explore the evidence around clozapine re-challenge following
      myocarditis. CONCLUSION: This case adds to the 17 cases of clozapine re-challenge
      following myocarditis, of which 71% were successful (12 cases). This demonstrates
      that re-challenge could be performed safely and effectively in the context of
      clozapine-induced myocarditis, if accompanied by a strict and rigorous monitoring
      protocol.

PMID- 28506080
TI  - Hepatocellular carcinoma treatment: a comparative review of emerging growth
      factor receptor antagonists.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of death
      worldwide. Over the last decade, sorafenib has been the only available
      therapeutic option for advanced HCC, although regorafenib recently showed a
      survival benefit compared with placebo in a second-line setting. Areas covered:
      This review discusses key published and ongoing studies with targeted agents in
      HCC, molecular targets of HCC, the mechanism of resistance to sorafenib, and the
      role of biomarker-enriched clinical trials. Expert opinion: The multiplicity of
      drivers and the existence of substantial molecular heterogeneity limit the
      benefits of targeted therapies in HCC. Based on molecular biology developments, a
      few biomarker-enriched clinical trials that target candidate driver genes are
      ongoing, and the outcomes of these are highly anticipated. Poor availability of
      tumor tissue and tumor heterogeneity in patients with HCC make liquid biopsy a
      very attractive option, although this technique remains to be validated.

PMID- 28506079
TI  - The Neural Correlates of Emotional Lability in Children with Autism Spectrum
      Disorder.
AB  - Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical
      and physiopathological presentations. Clinical variability applies to ASD
      specific symptoms and frequent comorbid psychopathology such as emotional
      lability (EL). To date, the physiopathological underpinnings of the co-occurrence
      of EL and ASD are unknown. As a first step, we examined within-ASD inter
      individual variability of EL and its neuronal correlates using resting-state
      functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58
      children diagnosed with ASD (5-12 years) in relation to the Conners' Parent
      Rating Scale EL index. We performed both an a priori amygdala region-of-interest
      (ROI) analysis, and a multivariate unbiased whole-brain data-driven approach.
      While no significant brain-behavior relationships were identified regarding
      amygdala intrinsic functional connectivity (iFC), multivariate whole-brain
      analyses revealed an extended functional circuitry centered on two regions:
      middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and
      nonparametric ROI-analyses of these regions revealed relationships between EL and
      MFG- and PI-iFC with default, salience, and visual networks suggesting that
      higher-order cognitive and somatosensory processes are critical for emotion
      regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in
      ASD. However, exploratory whole-brain analyses identified large-scale networks
      that have been previously reported abnormal in ASD. Future studies should
      consider EL as a potential source of neuronal heterogeneity in ASD and focus on
      multinetwork interactions.

PMID- 28506081
TI  - Epidemiological characteristics of Chinese paediatric traumatic brain injury
      inpatients.
AB  - PRIMARY OBJECTIVE: To investigate the epidemiological characteristics of
      paediatric inpatients with traumatic brain injury (TBI) in China. RESEARCH
      DESIGN: The Chinese Trauma Database (CTD), a nationwide register system based on
      hospital admission data, contains diagnosis and treatment information for trauma
      inpatients in over 200 military-managed public-service hospitals in China. Using
      the ICD-9 coding, the data for children with TBI aged 0-17 years between 2001 and
      2007 were retrieved. METHODS AND PROCEDURES: The demographic characteristics,
      admission time, injury cause, severity and treatment outcomes of paediatric
      inpatients with TBI were analysed. MAIN OUTCOMES AND RESULTS: A total of 26,028
      paediatric inpatients with TBI (69.52% male, 30.48% female) were included in the
      CTD. Motor vehicle traffic (MVT) accidents, falls and assaults were the primary
      causes of injury. Falls were the leading cause of TBI in children aged 0-4 years,
      and MVT was the leading cause of TBI in children aged 5-17 years. According to
      the abbreviated injury scale, 37.20% of the TBI cases were mild, 25.15% were
      moderate, 24.81% were severe and 12.84% were critically severe. CONCLUSION:
      Chinese authorities should develop targeted measures to reduce children injuries
      based on the leading causes of TBI in the different age groups, particularly MVT,
      falls and assaults.

PMID- 28506082
TI  - Novel Use of Active Leptospermum Honey for Ringed Fixator Pin Site Care in
      Diabetic Charcot Deformity Patients.
AB  - INTRODUCTION: Open reduction with external fixation (OREF) utilizing fine wire
      ringed fixators for correction of Charcot deformity has gained popularity over
      the past decade. Pin site infections are a well-documented complication of
      external fixation as well as a driver of escalating health care costs. We aimed
      to demonstrate the safety and efficacy of a novel method of pin site care
      utilizing active Leptospermum honey-impregnated dressings (MediHoney) in diabetic
      patients undergoing deformity correction with OREF. METHODS: Twenty-one diabetic
      patients with Charcot deformities of the lower extremity were prospectively
      enrolled and followed for pin site complications following OREF for deformity
      correction. Active Leptospermum honey dressings were applied at metal-cutaneous
      interfaces at the end of the OREF procedure and replaced weekly for a total of 8
      weeks. Patients were monitored for pin site infections from the time of surgery
      until external fixator removal. Sixteen consecutive patients receiving standard
      OREF for Charcot deformities were evaluated retrospectively to serve as a control
      group. RESULTS: Of the 21 enrolled patients, 19 underwent OREF and followed up
      throughout the study period. Treated patients had a mean age of 58.5 years and
      mean body mass index measuring 33.3 kg/m2 as documented prior to surgery. The 15
      patients with hemoglobin A1c labs drawn in the 3 months preceding surgery
      averaged 7.5. Fixators were removed at an average of 12.1 weeks after adequate
      bony healing. Of the 244 pin sites in 19 patients, 3 pin sites (1.2% of pins) in
      2 patients (10.5% of patients) showed evidence of superficial infection. All
      infections resolved with oral antibiotics. Infection rates were significantly
      reduced when compared to the standard care control group. CONCLUSIONS: Pilot data
      in a prospectively collected case series demonstrate safety and efficacy of
      active Leptospermum honey-impregnated dressings when used for fine wire ringed
      fixator pin site care in diabetic Charcot deformity patients. Further
      investigation in the form of a prospective randomized controlled study is
      warranted to demonstrate the potential value of this novel intervention. LEVELS
      OF EVIDENCE: Level IV.

PMID- 28506083
TI  - Ultrasound-Guided Percutaneous Needle Fenestration and Corticosteroid Injection
      for Anterior and Anterolateral Ankle Impingement.
AB  - BACKGROUND: Ankle impingement is a common cause of chronic ankle pain. We
      retrospectively studied the effectiveness of ultrasound-guided percutaneous
      needle fenestration of the pathological soft tissues combined with corticosteroid
      injection to treat this condition. METHODS: We administered a telephone survey to
      patients who underwent the procedure. Patients were asked questions on the Foot
      Function Index and queried about their overall satisfaction with the procedure on
      a scale of 0 (completely unsatisfied) to 10 (very satisfied). RESULTS: Forty-nine
      patients participated in the survey: 26 women and 23 men, mean age 42.7 years
      (range, 19-65 years). Impingement was anterior in 26/49 (53.1%), anterolateral in
      14/49 (28.6%), and both in 9/49 (18.4%). Mean pain level before the procedure was
      6.76 +/- 1.84 and after the procedure was 2.73 +/- 2.21. Reported pain scale
      levels declined by 4.02 +/- 2 units after the procedure (P < .0001). Patient's
      overall satisfaction was 7.9 +/- 2.44. CONCLUSIONS: Ultrasound-guided
      percutaneous needle fenestration and corticosteroid injection appears to be an
      effective nonoperative alternative for treatment of anterior and/or anterolateral
      ankle impingement. LEVELS OF EVIDENCE: Level IV.

PMID- 28506084
TI  - Turmeric: old spice, new spice.
AB  - The history of chemical investigations into the yellow components of turmeric can
      be traced from 1815. Although the major yellow component of turmeric, curcumin,
      often is represented as a 1,3-diketone in the solid state and in nonaqueous
      solution, it exists in the enol form. The struggle to identify the chemical
      structure of curcumin continued for nearly a century and was complicated by the
      difficult purification of curcumin and by the presence of two additional yellow
      components. Food remains the main use for turmeric (old spice); its use as a dye
      has diminished since the 19th century, but it may have pharmaceutical uses (new
      spice).

PMID- 28506085
TI  - Long-term exposure to a continuous 900 MHz electromagnetic field disrupts
      cerebellar morphology in young adult male rats.
AB  - The pathological effects of exposure to an electromagnetic field (EMF) during
      childhood and adolescence may be greater than those from exposure during
      adulthood. We investigated possible pathological changes in the cerebellum of
      adolescent rats exposed to 900 MHz EMF daily for 25 days. We used three groups of
      six 21-day-old male rats as follows: unexposed control group (Non-EG), sham
      exposed group (Sham-EG) and an EMF-exposed group (EMF-EG). EMF-EG rats were
      exposed to EMF in an EMF cage for 1 h daily from postnatal days 21 through 46.
      Sham-EG rats were placed in the EMF cage for 1 h daily, but were not subjected to
      EMF. No procedures were performed on the Non-EG rats. The cerebellums of all
      animals were removed on postnatal day 47, sectioned and stained with cresyl
      violet for histopathological and stereological analyses. We found significantly
      fewer Purkinje cells in the EMF-EG group than in the Non-EG and Sham-EG groups.
      Histopathological evaluation revealed alteration of normal Purkinje cell
      arrangement and pathological changes including intense staining of neuron
      cytoplasm in the EMF-EG group. We found that exposure to continuous 900 MHz EMF
      for 1 h/day during adolescence can disrupt cerebellar morphology and reduce the
      number of Purkinje cells in adolescent rats.

PMID- 28506086
TI  - Invasive cardiopulmonary exercise testing in the evaluation of unexplained
      dyspnea: Insights from a multidisciplinary dyspnea center.
AB  - Background Unexplained dyspnea is a common diagnosis that often results in
      repeated diagnostic testing and even delayed treatments while a determination of
      the cause is being investigated. Through a retrospective study, we evaluated the
      diagnostic efficacy of a multidisciplinary dyspnea evaluation center (MDEC) using
      invasive cardiopulmonary exercise test to diagnose potential causes of
      unexplained dyspnea. Methods We reviewed the medical records of all patients
      referred with unexplained dyspnea to the MDEC between March 2011 and October
      2014. We assessed the diagnostic efficacy before and after presentation to the
      MDEC. Results During the study period a total of 864 patients were referred to
      the MDEC and, of those, 530 patients underwent further investigation with
      invasive cardiopulmonary exercise test and constituted the study sample. The
      median age was 57 (44-68) years, 67.2% were women, and median body mass index was
      26.22 (22.78-31.01). A diagnosis was made in 530 patients including: exercise
      pulmonary arterial hypertension of 88 (16.6%), heart failure with preserved
      ejection fraction of 94 (17.7%), dysautonomia 112 (21.1%), oxidative myopathy of
      130 (24.5%), primary hyperventilation of 43 (8.1%), and other 58 (10.9%). The
      time from initial presentation to referral was significantly longer than time to
      diagnosis after referral for non-standardized conventional methods versus
      diagnosis through MDEC using invasive cardiopulmonary exercise test (511 days
      (292-1095 days) vs. 27 days (13-53 days), p < 0.0001). In a subgroup analysis, we
      reviewed that patients referred from cardiovascular clinics were more likely to
      have a greater number of diagnostic tests performed and, conversely, patients
      referred from pulmonary clinics were more likely to have a greater number of
      treatments prescribed before referral to MDEC. Conclusions As a result of this
      retrospective study, we have evaluated that a multidisciplinary approach that
      includes invasive cardiopulmonary exercise test dramatically reduces the time to
      diagnosis compared with traditional treatment and testing methods.

PMID- 28506087
TI  - Differential variations of autophagy and apoptosis in permanent focal cerebral
      ischaemia rat model.
AB  - OBJECTIVE: Autophagy and apoptosis coexist in stroke, but the relationship
      between effects and complex is poorly understood. Herein, we investigated dynamic
      changes of autophagy and apoptosis at the penumbra in permanent cerebral
      ischaemia. METHODS: Sprague-Dawley rat models were prepared by middle cerebral
      artery occlusion. The autophagy and apoptosis were evaluated by Western blotting
      and immunofluorescence with LC3-II and cleaved caspase-3, respectively. The
      neurological deficit score and infarct volume were assessed. RESULTS: The results
      showed that the expressions of LC3-II and cleaved caspase-3 were gradually
      increased from 1 to 5 hours, and reached maximum at 5 hours after stroke. After
      that, LC3-II expression was significantly declined, but cleaved caspase-3
      expression was only mildly reduced from 6 hours to 3 days. Surprisingly, at 4
      days after stroke, the autophagy was abruptly increased again, but the apoptosis
      was considerably and continuously decreased. The severity of the neurological
      deficit was in accordance with the increase of infarct expansion. CONCLUSIONS:
      Our results showed that autophagy and apoptosis were simultaneously activated
      within 12 hours after stroke. Four days later, LC3-II expression was
      significantly increased, while cleaved caspase-3 expression was considerably
      decreased, implying that there might be a transition from apoptosis to autophagy
      at the subacute phase of stroke.

PMID- 28506088
TI  - Trends in white blood cell and platelet indices in a comparison of patients with
      papillary thyroid carcinoma and multinodular goiter do not permit differentiation
      between the conditions.
AB  - AIM: Carcinogenesis has been related to systematic inflammatory response. Our aim
      was to study white blood cell and platelet indices as markers of this
      inflammatory response in thyroid cancer and to associate them with various
      clinicopathological parameters. METHODS: We included 228 patients who underwent
      thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma
      and 139 with multinodular hyperplasia. We examined potential links between white
      blood cell and platelet indices on the one hand and the type thyroid pathology
      and various clinicopathological parameters on the other. RESULTS: No significant
      differences were detected between thyroid cancer and multinodular hyperplasia and
      no significant associations were detected with regard to lymphovascular invasion
      and tumor size. However, the mean platelet volume was higher in multifocal
      tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio
      were increased in cases with extrathyroidal extension and in T3 tumors.
      Additionally, T3 tumors had lower platelet distribution width. These associations
      demonstrated low accuracy in predicting these pathological features, but they
      were found to provide a satisfying negative predictive value, with the exception
      of the mean platelet volume. CONCLUSIONS: White blood cell and platelet indices
      cannot assist in distinguishing benign goiter from thyroid cancer. However, they
      can provide information about tumor multifocality, extrathyroidal extension, and
      presence of a T3 tumor, and they may be used as a means to exclude these
      pathological characteristics, especially the last two, in papillary thyroid
      carcinoma.

PMID- 28506089
TI  - Long-Term Oxygen Therapy in COPD Patients Who Do Not Meet the Actual
      Recommendations.
AB  - Chronic respiratory failure due to chronic obstructive pulmonary disease (COPD)
      is an increasing problem worldwide. Many patients with severe COPD develop
      hypoxemic respiratory failure during the natural progression of disease. Long
      term oxygen therapy (LTOT) is a well-established supportive treatment for COPD
      and has been shown to improve survival in patients who develop chronic hypoxemic
      respiratory failure. The degree of hypoxemia is severe when partial pressure of
      oxygen in arterial blood (PaO2) is <=55 mmHg and moderate if PaO2 is between 56
      and 69 mmHg. Although current guidelines consider LTOT only in patients with
      severe resting hypoxemia, many COPD patients with moderate to severe disease
      experience moderate hypoxemia at rest or during special circumstances, such as
      while sleeping or exercising. The efficacy of LTOT in these patients who do not
      meet the actual recommendations is still a matter of debate, and extensive
      research is still ongoing to understand the possible benefits of LTOT for
      survival and/or functional outcomes such as the sensation of dyspnea,
      exacerbation frequency, hospitalizations, exercise capacity, and quality of life.
      Despite its frequent use, the administration of "palliative" oxygen does not seem
      to improve dyspnea except for delivery with high-flow humidified oxygen. This
      narrative review will focus on current evidence for the effects of LTOT in the
      presence of moderate hypoxemia at rest, during sleep, or during exercise in COPD.

PMID- 28506091
TI  - Reaching the Unreachable: Novel Approaches to Telemedicine Screening of
      Underserved Populations for Vitreoretinal Disease.
AB  - Telemedicine involves electronic communication between a physician in one
      location and a patient in another location to provide remote medical care.
      Ophthalmologists are increasingly employing telemedicine, particularly in retinal
      disease screening and monitoring. Telemedicine has been utilized to decrease
      barriers to care and yield greater patient satisfaction and lower costs, while
      maintaining high sensitivity and specificity. This review discusses common
      patient barriers to eye care, innovative approaches to retinal disease screening
      and monitoring using telemedicine, and eye care policy initiatives needed to
      enact large-scale telemedicine eye disease screening programs.

PMID- 28506093
TI  - The Virtual Short Physical Performance Battery: Psychometric Properties and
      Validation in Older Adults With Multiple Sclerosis.
AB  - BACKGROUND: There are increasing numbers of older adults with multiple sclerosis
      (MS) who undergo declines in physical function that require attention of
      clinicians and researchers. Objective and perceived measures of disablement
      feasible for clinical and residential settings, such as the Short Physical
      Performance Battery and its virtual counterpart (vSPPB), are critical for
      defining the degree of disablement. OBJECTIVE: We evaluated the psychometric
      properties and validity of the vSPPB as a measure of perceived lower extremity
      physical function in older adults with MS (age >=60 years). METHOD: The sample
      included 35 older adults with MS and 35 age- and sex-matched healthy controls
      (age >=60 years) who completed a battery of assessments, including the vSPPB.
      RESULTS: The vSPPB performed satisfactorily in older adults with MS regarding
      data quality, scaling assumptions, and acceptability (i.e., psychometrics). The
      vSPPB further demonstrated criterion, known-groups, convergent, and discriminant
      construct validity. CONCLUSION: This report provides evidence for the validity of
      vSPPB scores as a measure of perceived lower extremity physical function in older
      adults with MS.

PMID- 28506092
TI  - Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of
      Disease Risk and Treatment Response.
AB  - The beta2-adrenergic receptor (ADRB2) is an important regulator of airway smooth
      muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair
      ADRB2 function could increase disease risk or reduce the response to endogenous
      and inhaled adrenergic agonists in COPD. We performed a systematic review and
      three meta-analyses to assess whether three functional variants (Thr164Ile,
      Arg16Gly, and Gln27Glu) in the ADRB2 gene are associated with elevated risk of
      disease or reduced therapeutic response to inhaled beta2-agonists in COPD. We
      searched the medical literature from 1966 to 2017 and found 16 relevant studies
      comprising 85381 study subjects. The meta-analyses found no significant
      association between ADRB2 genotype and COPD risk. The summary odds ratios (ORs)
      for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence
      interval (CI): 0.54-12.4) and 1.17 (95% CI: 0.96-1.44), respectively.
      Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were
      0.97 (95% CI: 0.76-1.22) and 1.01 (95% CI: 0.81-1.26), while summary ORs for COPD
      in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80-1.25) and 0.94
      (95% CI: 0.69-1.24), respectively. When stratified by ethnicity, the summary ORs
      for COPD did not differ from 1.0 for any of the ADRB2 variants among Asian,
      Caucasian, or African populations. We found no consistent associations between
      ADRB2 genotype and treatment response to inhaled beta2-agonists in COPD. This
      systematic review and meta-analyses found that COPD risk and response to inhaled
      beta2-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu
      genotypes. However, identified cases of Thr164Ile were few, and additional
      studies of rare ADRB2 genotypes are required.

PMID- 28506094
TI  - A preliminary study of youth sport concussions: Parents' health literacy and
      knowledge of return-to-play protocol criteria.
AB  - PRIMARY OBJECTIVE: To preliminarily explore parents' health literacy and
      knowledge of youth sport league rules involving concussion education and
      training, and return-to-play protocols. RESEARCH DESIGN AND METHODS: This study
      was guided by the Knowledge, Attitude and Practice (KAP) model of health
      knowledge to examine parents' concussion literacy, and understanding of
      concussion education and training, and return-to-play protocols in youth sports.
      The mixed-method design involved 119 participants; that included in-person (n=8)
      and telephone (n=4) interviews, and web-based surveys administered through
      Mechanical Turk via Qualtrics (n=98). MAIN OUTCOMES AND RESULTS: Most respondents
      were not familiar with concussion protocols, but trusted coaches' knowledge in
      return-to-play rules. More than half of the respondents report that the return-to
      play concussion criteria have not been clearly explained to them. The majority of
      respondents were not familiar with the CDC's 'Heads Up' online concussion
      training programme, nor were they familiar with any other educational/training
      tool. About one-fifth of the parents had conversations with a coach or medical
      staff about youth sport concussions. CONCLUSION: Parents have a general
      understanding of how to identify concussion symptoms, but lack knowledge of
      immediate steps to take following an incident other than seeking medical help.

PMID- 28506090
TI  - Rational design strategies for FimH antagonists: new drugs on the horizon for
      urinary tract infection and Crohn's disease.
AB  - INTRODUCTION: The bacterial adhesin FimH is a virulence factor and an attractive
      therapeutic target for urinary tract infection (UTI) and Crohn's Disease (CD).
      Located on type 1 pili of uropathogenic E. coli (UPEC), the FimH adhesin plays an
      integral role in the pathogenesis of UPEC. Recent efforts have culminated in the
      development of small-molecule mannoside FimH antagonists that target the mannose
      binding lectin domain of FimH, inhibiting its function and preventing UPEC from
      binding mannosylated host cells in the bladder, thereby circumventing infection.
      Areas covered: The authors describe the structure-guided design of mannoside
      ligands, and review the structural biology of the FimH lectin domain.
      Additionally, they discuss the lead optimization of mannosides for therapeutic
      application in UTI and CD, and describe various assays used to measure mannoside
      potency in vitro and mouse models used to determine efficacy in vivo. Expert
      opinion: To date, mannoside optimization has led to a diverse set of small
      molecule FimH antagonists with oral bioavailability. With clinical trials already
      initiated in CD and on the horizon for UTI, it is the authors, opinion that
      mannosides will be a 'first-in-class' treatment strategy for UTI and CD, and will
      pave the way for treatment of other Gram-negative bacterial infections.

PMID- 28506095
TI  - Understanding attitudes toward information and communication technology in home
      care: Information and communication technology as a market good within Norwegian
      welfare services.
AB  - The aim of this study was to better understand nurses' and other staff members'
      attitudes toward the usefulness of information and communication technology in
      home-care settings. Research has found that beliefs about the expected benefits
      of information and communication technology impact the use of technology.
      Furthermore, inexperience with using information and communication technology may
      cause negative attitudes. This article is based on a questionnaire to 155 nurses
      and other staff members in home-care in Sogn og Fjordane county in Norway. The
      results revealed minimal use of information and communication technology at work;
      however, participants had positive attitudes regarding the potential benefits of
      information and communication technology use in home-care. Individuals' extensive
      use of and familiarity with different solutions in private lives could be an
      important context for explaining employees' attitudes. Given that information and
      communication technology is both a welfare service and a market good, this may
      explain individuals' positive attitudes toward information and communication
      technology despite their lack of experience with it at work. Experiences with
      information and communication technology as a market good and the way new
      technologies can affect work routines will affect the implementation of
      information and communication technology in home-care.

PMID- 28506096
TI  - Response to: The cost of caring.

PMID- 28506097
TI  - A computational model of the [Formula: see text] transients and influence of
      buffering in guinea pig urinary bladder smooth muscle cells.
AB  - Many cellular events including electrical activity and muscle contraction are
      regulated and coordinated by intracellular [Formula: see text] concentration
      ([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells,
      [[Formula: see text]]i is normally maintained at very low levels and rises
      transiently during signalling processes as a result of (i) influx from the
      extracellular space (mainly via L-type and T-type [Formula: see text] channels)
      and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the
      cytoplasm. Intracellular [Formula: see text] buffers, both fixed and diffusible,
      play a vital role in shaping the radial distribution of free [Formula: see text].
      Our aim, in the work presented here, is to develop a mathematical model of
      [Formula: see text] buffering and diffusion and to generate [Formula: see text]
      transient in guinea pig DSM cells. The [Formula: see text] transient is generated
      using inward [Formula: see text] current that arises following voltage clamp and
      mediated by L-type and T-type [Formula: see text] channels. [Formula: see text]
      transient is obtained for different radial locations (or shells) of the DSM
      cytosol. This modeling study explores the levels of [[Formula: see text]]i
      achieved near the plasma membrane and in deeper locations. The [Formula: see
      text] transient generated in our model shows a high degree of similarity with
      experimental findings in terms of amplitude, duration and half-decay time. A
      number of different buffer properties such as concentration and mobility are
      tested for their effect on amplitude and shape of [Formula: see text] transient.
      The presence of fast buffer concentration in the cytosol markedly delays the rise
      of [[Formula: see text]]i in the core of the cell. Increase in the mobility of
      fast buffer slightly speeds up the redistribution of [Formula: see text]. To
      explore the model further, the role of plasma membrane [Formula: see text]-ATPase
      (PMCA) pump, sarcoplasmic/endoplasmic reticulum [Formula: see text]-ATPase
      (SERCA) pump and sodium calcium exchanger (NCX) on [Formula: see text] transient
      is studied and it is suggested that NCX may be of primary importance for the
      immediate lowering of [[Formula: see text]]i during the falling phase of a
      [Formula: see text] transient in DSM cells.

PMID- 28506098
TI  - Long-term influence of sialoadenectomy on the liver of male albino rat.
AB  - Epidermal growth factor is an endocrine product of the submandibular gland; the
      liver is an important target of its action and is affected by sialoadenectomy.
      Thirty rats were used in this study and divided into group I (sham-operated
      animals), group II (sialoadenectomy after 4 weeks), and group III
      (sialoadenectomy after 10 weeks). Liver samples were processed for light and
      electron microscope examination. Sialoadenectomy induced mild-to-moderate liver
      damage which persists up to 10 weeks after the operation. This damage is
      manifested morphologically rather than functionally, affecting the general
      structure, hepatocytes, hepatic stellate cells, and hepatic sinusoids.

PMID- 28506099
TI  - Propofol-Based Palliative Sedation to Treat Antipsychotic-Resistant Agitated
      Delirium.
AB  - Delirium is a common problem in terminally ill patients that is associated with
      significant distress and, hence, considered a palliative care emergency. The
      three subtypes of delirium are hyperactive, hypoactive, and mixed, depending on
      the level of psychomotor activity and arousal disturbance. When agitated delirium
      becomes refractory in the setting of imminent dying, the agitation may be so
      severe that palliative sedation (PS) is required. Palliative sedation involves
      the administration of sedative medications with the purpose of reducing level of
      consciousness for patients with refractory suffering in the setting of a terminal
      illness. Propofol is a sedative that has a short duration of action and a very
      rapid onset. These characteristics make it relatively easy to titrate. Reported
      doses range from 50 to 70 mg per hour. The authors present a case of
      antipsychotic-resistant agitated delirium treated with a propofol intravenous
      infusion.

PMID- 28506100
TI  - Diagnostic performance of CTLA-4, carcinoembryonic antigen and CYFRA 21-1 for
      malignant pleural effusion.
AB  - OBJECTIVES: The diagnosis of malignant pleural effusion (MPE) remains a clinical
      challenge. As a negative regulator of T-cell activation, cytotoxic T lymphocyte
      associated antigen-4 (CTLA-4) has been associated with many malignant diseases.
      However, there is limited data about the relationship between CTLA-4 and MPE. The
      present study aims to investigate whether CTLA-4 levels may correlate with
      presence of MPE and to assess its potential diagnostic accuracy relative to that
      of the established markers carcinoembryonic antigen (CEA) and cytokeratin 19
      fragment (CYFRA21-1). METHODS: Pleural effusion samples were collected from 36
      patients with MPE and 48 patients with benign pleural effusion (BPE). Pleural
      levels of CTLA-4 were measured by ELISA; levels of CEA and CYFRA 21-1, by
      electrochemiluminescence immunoassay. Receiver operating characteristic curves
      were calculated to evaluate the ability of CTLA-4, CEA and CYFRA 21-1 to
      differentiate MPE from BPE. RESULTS: Pleural levels of CTLA-4 were significantly
      higher in MPE than in BPE patients (471.73 +/- 378.86 vs. 289.22 +/- 173.67
      pg/ml, p = 0.004). At a cut-off value of 351.25 pg/ml, the sensitivity and
      specificity of CTLA-4 in diagnosing MPE were 58.30% and 83.30%, respectively, and
      the area under the curve was 0.72. Pleural levels of CEA and CYFRA 21-1 were also
      higher in MPE. Using the combination of CTLA-4, CEA and CYFRA 21-1 increased
      diagnostic sensitivity to 88.89% and the area under the curve to 0.92.
      CONCLUSION: The results of this preliminary study suggest that increased levels
      of CTLA-4 correlate with MPE, and that CTLA-4 may have some diagnostic usefulness
      when used in combination with conventional tumor markers such as CEA and CYFRA 21
      1. These results justify larger, more rigorous studies to validate our findings.

PMID- 28506102
TI  - Reappraising the Impact of Offending on Victimization: A Propensity Score
      Matching Approach.
AB  - Existing evidence clearly supports an empirical connection between offending and
      victimization. Often called the "victim-offender overlap," this relationship
      holds for both sexes, across the life course, and across a wide range of
      countries and cultural environments. In addition, the relationship is sustained
      regardless of the study sample and statistical methods applied in the analyses of
      the sample data. However, there has yet to be a study that examines this
      relationship for violent and property crime using quasi-experimental methods
      accounting for a wide range of potential confounders including individual
      differences and cultural contexts. This study subjects the victim-offender
      relationship to testing through propensity score matching for both violent and
      property crimes using an international dataset. The results show that previous
      violent and theft offending increases the odds of victimization when matching on
      individual and contextual factors. This finding supports previous literature and
      suggests that delinquent behavior may act as a "switch" that exposes one to
      subsequent violent and theft victimization.

PMID- 28506101
TI  - Evaluation of personal inhalable aerosol samplers with different filters for use
      during anthrax responses.
AB  - Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores
      has primarily been assessed using short-term, stationary sampling methods which
      may not accurately characterize the concentration of inhalable-sized spores
      reaching a person's breathing zone. While a variety of aerosol sampling methods
      have been utilized during previous anthrax responses, no consensus has yet been
      established for personal air sampling. The goal of this study was to determine
      the best sampler-filter combination(s) for the collection and extraction of B.
      anthracis spores. The study was designed to (1) evaluate the performance of four
      filter types (one mixed cellulose ester, MCE (pore size = 3 um), two
      polytetrafluoroethylene, PTFE (1 and 3 um), and one polycarbonate, PC (3 um));
      and (2) evaluate the best performing filters in two commercially available
      inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki
      [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The
      filters were assessed based on criteria such as ability to maintain low pressure
      drop over an extended sampling period, filter integrity under various
      environmental conditions, spore collection and extraction efficiencies, ease of
      loading and unloading the filters into the samplers, cost, and availability.
      Three of the four tested collection filters-except MCE-were found suitable for
      efficient collection and recovery of Bt(k) spores sampled from dry and humid as
      well as dusty and clean air environments for up to 8 hr. The PC (3 um) filter was
      identified as the best performing filter in this study. The PTFE (3 um)
      demonstrated a comparable performance, but it is more expensive. Slightly higher
      concentrations were measured with the IOM inhalable sampler which is the
      preferred sampler's performance criterion when detecting a highly pathogenic
      agent with no established "safe" inhalation exposure level. Additional studies
      are needed to address the effects of environmental conditions and spore
      concentration. The data obtained in this investigation are crucial for future
      efforts on the development and optimization of a method for assessing inhalation
      exposure to B. anthracis.

PMID- 28506103
TI  - Treatment-Seeking Behaviors of Persons With Rheumatoid Arthritis.
AB  - PURPOSE: Describe perceptions of patients with rheumatoid arthritis (RA)
      regarding disease-related pain, tendency to tell others about their pain, and
      treatments used since diagnosis. DESIGN: Cross sectional, exploratory. METHOD: A
      total of 63 participants responded to telephone interview about their treatments
      and tendency to tell others about their RA pain. They also responded to McGill
      Pain Questionnaire and Health Assessment Questionnaire (HAQ) items. Participants
      marked pain location on mailed body outlines. FINDINGS: RA diagnosis occurred an
      average of 11 years prior. Mean HAQ Standard Disability Index score was 1.26.
      Previous week symptoms were joint pain (97%), joint swelling (83%), decreased
      movement/function (83%), fatigue (70%), muscle weakness (65%). Mean morning
      stiffness duration was 120 +/- 137 minutes. Mean pain intensity was 1.15 +/- 0.6
      at its least and 3.8 +/- 1.1 at its worst. 65% were not satisfied with pain
      levels. 57% stated a tendency not to tell others about their pain; 43% tended to
      tell. 78% used medications and alternative therapies, none solely used
      alternative therapies, and 22% only used medications. CONCLUSIONS: RA patients
      reported high rates of alternative therapy use. Dissatisfaction with pain levels
      indicates need for improved pain management. Not talking about pain lends
      insights into the importance of teaching patients to communicate their pain to
      others.

PMID- 28506104
TI  - Application of weak ultrasonic treatment on sludge electro-osmosis dewatering.
AB  - Ultrasonic treatment is a good method of facilitating sewage sludge dewatering
      characteristics. It can also promote the potential of sludge electro-osmosis
      dewatering (EDW), which is an accepted method of deep dewatering, but the
      treatment method and optimizing conditions should be determined by performing
      experiments. In this study, we consider two treating methods: ultrasonic pre
      treatment, which uses ultrasonic treatment as sludge pre-treatment before electro
      osmosis dehydration, and ultrasonic coupling, which uses ultrasonic and electric
      fields simultaneously. Using sludge from the Tianjin Jizhuangzi sewage treatment
      plant, we analyze the influence of ultrasonic intensity and treatment time on
      sludge dewatering by performing two different methods. The results show that they
      effectively facilitated sludge EDW. Under the same conditions, i.e. 2 cm cake
      initial thickness, voltage of 60 V for 5 min, and 0.1 MPa mechanical pressure for
      5.5 min, the optimum processing conditions for ultrasonic pre-treatment were
      found to be 0.510 W/cm2 and 3.5 min, the dehydration rate reached 34.71%, and the
      optimum conditions for ultrasonic coupling were 0.255 W/cm2 and 3.5 min, while
      the dehydration rate reached 40.78%. The dehydration rates for both approaches
      were clearly better than 17.40%, which was obtained under pure electro-osmosis
      dehydration. To compare the effects of ultrasonic pre-treatment and ultrasonic
      coupling on the electro-osmosis dehydration process, in this paper, we present
      the curves of dehydration rate, electric current, electro-osmosis flow, and
      scanning electron microscopy for dewatered sludge. Compared with the ultrasonic
      pre-treatment method, the effect of ultrasonic coupling on electro-osmosis
      dehydration was more obvious.

PMID- 28506105
TI  - Evaluating the Types of Pharmacy Student Interventions Made During an
      Interprofessional 6-Week Adult Internal Medicine Rotation.
AB  - INTRODUCTION: The new standards for pharmacy education require that pharmacy
      students are involved in direct and interprofessional team-based care in multiple
      practice settings, which include "real-time" interactions with physician
      prescribers and medical students. METHODS: From April 2014 to December 2015,
      fourth-year Doctor of Pharmacy (PharmD) students at University Medical Center of
      El Paso, Texas were assigned to an interprofessional team that was comprised of
      physician prescribers, medical students, and a pharmacist faculty. They recorded
      their interventions that were analyzed for type, number, physician acceptance,
      clinical importance, and time requirements for intervention recommendation.
      Interventions were divided into 5 main types and further divided into specific
      categories. RESULTS: Twelve PharmD students contributed 531 interventions,
      resulting in an average of 44 interventions per student with a physician
      acceptance rate of 87%. The most common types of interventions performed by
      PharmD students were under the categories of Therapy Needed (29.8%), Too Low
      Dose/Frequency (21.1%), Too High Dose/Frequency (8.3%), Therapeutic Level
      Monitoring (6.8%), and IV to PO Conversion (4.9%). A majority of interventions
      were of moderate clinical importance (56.1%) and took approximately 15 minutes to
      complete (92.5%). CONCLUSION: PharmD students under the supervision of clinical
      faculty on an interprofessional internal medicine team are valuable collaborators
      and contributors in decreasing the number of drug-related problems that can
      negatively impact patient care.

PMID- 28506106
TI  - Management of Direct-Acting Oral Anticoagulants Surrounding Dental Procedures
      With Low-to-Moderate Risk of Bleeding.
AB  - The purpose of this article is to review the available evidence regarding how to
      safely manage direct-acting oral anticoagulant (DOAC) therapy in patients
      requiring dental procedures with low-to-moderate risk of bleeding. A literature
      search was performed using MEDLINE and PubMed. Each author performed an
      independent search to ensure all pertinent articles were identified. The
      reference sections of each article were also reviewed. Pertinent articles were
      evaluated by each author for inclusion. Articles were eligible for inclusion if
      the participants were taking DOAC therapy surrounding a dental procedure known to
      have low-to-moderate risk of bleeding. Studies could be prospective or
      retrospective and included case reports, case series, and clinical trials.
      Articles were excluded if they assessed dental procedures known to carry a high
      risk of bleeding or were review articles. Twenty-five articles were identified, 5
      of which met inclusion criteria including 2 case series, 1 retrospective study,
      and 2 prospective trials. Variation in the management of DOAC therapy surrounding
      these procedures was found. Among patients undergoing low-to-moderate risk dental
      procedures while receiving DOAC therapy, bleeding rates were low regardless of
      whether the DOAC was held or continued surrounding the procedure. Documented
      bleeding was mild and easily controlled by local hemostatic measures. Patients
      can safely continue DOAC therapy surrounding these dental procedures.

PMID- 28506107
TI  - Immunoassay approach for diagnosis of exposure to pyrrolizidine alkaloids.
AB  - Numerous pyrrolizidine alkaloid (PA) poisoning cases have been documented
      worldwide. Protein covalent binding with reactive metabolites generated from
      metabolic activation of PAs to form pyrrole-protein adducts is suggested to be a
      primary mechanism of PA-induced toxicities. The present study aimed to develop
      antibodies for diagnosis of PA exposure. Polyclonal antibodies were raised in
      rabbits and proven to specifically recognize pyrrole-protein adducts regardless
      of amino acid residues modified by the reactive metabolites of PAs. The developed
      antibodies were successfully applied to detect pyrrole-protein adducts in blood
      samples obtained from PA-treated rats and exhibited a potential for the clinical
      diagnosis of PA exposure.

PMID- 28506108
TI  - Age differences in self-set goal effects for memory.
AB  - Research has shown that goal setting leads to gains in memory performance and
      memory self-efficacy across adulthood when goals are set by experimenters and
      accompanied by positive feedback. However, self-set memory goals have had less
      consistent impact. This research extended past studies on aging and memory goals
      to examine the impact of self-set goals using anchors to guide goal selection.
      Two trials of name, text, and list recall were administered to younger and older
      adults, comparing goal and no-goal groups. After baseline, participants assigned
      to the goal group set personal goals for memory gain on a second, post-goal trial
      for each of the three tasks. Anchoring for goal-setting was used to encourage the
      selection of realistic, yet challenging goals. Younger and older participants set
      comparable goals. Only younger adults showed a motivational response (higher
      gains across trials for goals than no goals), even though older adults reported
      being just as committed to their personal goals. Older adults may have failed to
      show reliable goal-related gains because no positive feedback was offered or
      because they were unable to activate effective strategies for improved
      performance.

PMID- 28506109
TI  - Forgiveness, Attachment to God, and Mental Health Outcomes in Older U.S. Adults:
      A Longitudinal Study.
AB  - We analyze a sample of older U.S. adults with religious backgrounds in order to
      examine the relationships among two types of divine forgiveness and three
      indicators of psychological well-being (PWB) as well as the moderating role of
      attachment to God. Results suggest that (a) feeling forgiven by God and
      transactional forgiveness from God are not associated with changes in PWB over
      time, (b) secure attachment to God at baseline is associated with increased
      optimism and self-esteem, (c) feeling forgiven by God and transactional
      forgiveness from God are more strongly associated with increased PWB among the
      securely attached, and (d) among the avoidantly attached, PWB is associated with
      consistency in one's beliefs, that is, a decreased emphasis on forgiveness from
      God. Findings underscore the importance of subjective beliefs about God in the
      lives of many older adults in the United States.

PMID- 28506110
TI  - Evaluation of chemical mutagenicity using next generation sequencing: A review.
AB  - Mutations are heritable changes in the nucleotide sequence of DNA that can lead
      to many adverse effects. Genotoxicity assays have been used to identify chemical
      mutagenicity. Recently, next generation sequencing (NGS) has been used for this
      purpose. In this review, we present the progress in NGS application for assessing
      mutagenicity of chemicals, including the methods used for detecting the induced
      mutations, bioinformatics tools for analyzing the sequencing data, and chemicals
      whose mutagenicity has been evaluated using NGS. Available information suggests
      that NGS technology has unparalleled advantages for evaluating mutagenicity of
      chemicals can be applied for the next generation of mutagenicity tests.

PMID- 28506111
TI  - Re: "Comprehensive Survey Results of Childhood Thyroid Ultrasound Examinations in
      Fukushima in the First Four Years After the Fukushima Daiichi Nuclear Power Plant
      Accident" by Suzuki et al. (Thyroid 2016;26:843-851).

PMID- 28506112
TI  - Resting Bradycardia, Enhanced Postexercise Heart Rate Recovery and
      Cardiorespiratory Fitness in Recreational Ballroom Dancers.
AB  - PURPOSE: In a cross-sectional study design, we evaluated the resting heart rate
      (HRbaseline) and exercise and postexercise stress test-related chronotropic
      responses in male practitioners of recreational ballroom dancing (BD; n = 25,
      Mage = 26.6 +/- 6.1 years) compared to a control group of insufficiently active
      nondancers (CG; n = 25, Mage = 25.9 +/- 4.5 years). METHOD: All participants
      underwent a submaximal exercise test. At 85% of the maximal predicted HR, the
      recovery protocol was started, and heart rate recovery (HRR) was recorded during
      1-min intervals for 5 min. RESULTS: Compared with CG, BD showed lower HRbaseline
      (70 beats per minute [bpm] vs. 62 bpm, respectively, U = 143, p < .05, ES = .46),
      lower preexercise HR (94 bpm vs. 86 bpm, U = 157, p < .05, ES = .42), longer
      exercise test duration (346 s vs. 420 s, U = 95.5, p < .05, ES = .59), and higher
      HRR for 5 min postexercise (U = 1.29-1.89, p < .05, ES = .33-.50) as follows: 1st
      min (32 bpm vs. 40 bpm), 2nd min (45 bpm vs. 53 bpm), 3rd min (51 bpm vs. 58
      bpm), 4th min (55 bpm vs. 59 bpm), and 5th min (59 bpm vs. 63 bpm). The
      coefficient of HRR from the 1st min to the 5th min postexercise was similar in
      both groups (U = 229-311, p > .05, ES = < .10-.22). CONCLUSION: Heightened
      cardiovascular functional status characterized by favorable enhanced chronotropic
      dynamics appears to occur in practitioners of recreational ballroom dancing,
      which suggests that this modality of exercise may result in health benefits.

PMID- 28506113
TI  - The occurrence of ryegrass staggers and heat stress in sheep grazing ryegrass
      endophyte associations with diverse alkaloid profiles.
AB  - AIMS: To compare ryegrass pastures infected with endophytes producing diverse
      alkaloids for their ability to cause ryegrass staggers in grazing lambs; to
      compare respiration rates and rectal temperatures of these lambs after exposure
      to heat stress, and to compare liveweight gains during the study period. METHODS:
      Ryegrass pastures of cultivar Trojan infected with NEA endophytes, branded NEA2
      (T-NEA2), endophyte-free Trojan (T-NIL), Samson infected with standard endophyte
      (S-STD), Samson infected with AR37 endophyte (S-AR37) and endophyte-free Samson
      (S-NIL), were grazed by lambs (n=30 per cultivar) for up to 48 days in February
      and March of 2012 and 2013. Pasture samples were analysed for alkaloid
      concentrations and lambs were scored for ryegrass staggers at intervals during
      the study period. Liveweight was recorded at the start (Day 0) and end of the
      study, and rectal temperatures and respiratory rates were measured in lambs
      exposed to heat stress on Days 23 and 26, in 2012 and 2013, respectively.
      RESULTS: Concentrations of alkaloids were lower in 2012 than 2013, associated
      with warmer and drier conditions in 2013, and the prevalence of ryegrass staggers
      was low in 2012. In 2013, concentrations of ergovaline were similar in T-NEA2 and
      S-STD, but concentrations of lolitrem B were lower in T-NEA2 than S-STD. S-AR37
      produced epoxy-janthitrems but no lolitrem B or ergovaline. In 2013, by Day 20,
      9/30 (30%) sheep grazing S-STD had severe staggers (score >=4), and by Day 47 all
      sheep had been removed from this cultivar due to severe staggers. By Day 47,
      18/30 (60%), 4/30 (13%) and 0/30 (0%) sheep grazing S-AR37, T-NEA2 and T-NIL
      pastures, respectively, had severe staggers. There were no differences in mean
      daily weight gain of lambs between cultivars in either year. In both years, mean
      rectal temperature and respiration rate following exposure to heat stress were
      highest in sheep grazing S-STD and T-NEA2, and lowest in sheep grazing T-NIL.
      CONCLUSIONS: In lambs grazing different ryegrass pastures infected with
      endophytes, ryegrass staggers was most severe on S-STD, less severe on S-AR37 and
      least on T-NEA2. When under heat stress, lambs grazing ergovaline-producing S-STD
      and T-NEA2 pastures had increased respiration rates and rectal temperatures
      compared with lambs grazing T-NIL. CLINICAL RELEVANCE: If ambient temperatures
      are suitable, NEA2-branded endophytes have the potential to express
      concentrations of ergovaline sufficient to induce heat stress in grazing sheep.

PMID- 28506114
TI  - The Fatty Liver Index (FLI) Relates to Diabetes-Specific Parameters and an
      Adverse Lipid Profile in a Cohort of Nondiabetic, Dyslipidemic Patients.
AB  - BACKGROUND: Patients with hyperlipidemia are at high risk for developing a fatty
      liver. The fatty liver index (FLI) is a noninvasive and well-established method
      for the estimation of a fatty liver. However, little is known about the metabolic
      characterization of nondiabetic treated patients with hyperlipidemia who have
      different risk levels for a fatty liver. METHODS: In this study, 74 nondiabetic
      patients with hyperlipidemia were divided into 3 groups according to their fatty
      liver index. A comparison of metabolic characteristics was done. These
      characteristics included intima media thickness (IMT) and nutritional habits,
      which were further divided into FLI subgroups with low, intermediate, and high
      risk for a fatty liver. RESULTS: Patients with hyperlipidemia, with a high risk
      for a fatty liver (FLI >= 60), had subclinical elevations in parameters of
      carbohydrate metabolism (insulin, fasting plasma glucose, C-peptide) including a
      higher insulin resistance (quantitative insulin sensitivity check index, QUICKI)
      compared to lower FLI groups. These patients also presented a higher risk for a
      metabolic syndrome (p = 0.018), as well as an adverse lipid profile (e.g., high
      density lipoprotein [HDL] cholesterol, triglycerides [TG]-HDL ratio). FLI group 3
      was characterized by significantly lower levels of omega-3 fatty acids (p =
      0.048). CONCLUSION: The fatty liver index relates to diabetes-specific parameters
      and an adverse lipid profile and is an appropriate index for risk evaluation of
      metabolic syndrome.

PMID- 28506116
TI  - Intelligent Adaptive Systems: an interaction-centred design perspective.

PMID- 28506115
TI  - Predictors of work participation for Maori 3 months after injury.
AB  - An important rehabilitation outcome for injured Maori is a timely sustainable
      return to work. This article identifies the factors influencing working after
      injury in an attempt to reduce the individual, social, and economic costs. Maori
      participants in the Prospective Outcomes of Injury Study were interviewed about
      preinjury and injury-related factors. Among Maori participants, 521 were working
      for pay prior to injury; 64% were working 3 months postinjury. Factors
      identified, using modified Poisson regression, that predicted working include
      financial security (aRR = 1.34, 95% CI [1.12, 1.61]), an injury of low (aRR =
      1.76, 95% CI [1.26, 2.44]) or moderate severity (aRR = 1.86, 95% CI [1.34,
      2.59]), professional occupations (aRR = 1.22, 95% CI [1.03, 1.44]), and jobs with
      less repetitive hand movement (aRR = 1.17, 95% CI [1.01, 1.34]). These factors
      identified warrant attention when planning interventions to enable rehabilitation
      back to the workplace.

PMID- 28506117
TI  - Efficiency of a locally designed pilot-scale trickling biofilter (TBF) system in
      natural environment for the treatment of domestic wastewater.
AB  - In the present study, a cost-effective and simple stone media pilot-scale
      trickling biofilter (TBF) was designed, constructed and operated in a continuous
      recirculation mode for wastewater treatment with a hydraulic flow rate of 1.2
      L/min (Q = 0.072 m3/h) and hydraulic loading (Q/A) of 0.147 m3/day for 15 weeks
      at a temperature range of 14.5-36 degrees C. A substantial reduction in the
      average concentration of different pollution indicators, such as chemical oxygen
      demand (COD) (85.6%), biochemical oxygen demand (BOD5) (85.6%), total dissolved
      solid (TDS) (62.8%), total suspended solid (TSS) (99.9%), electrical conductivity
      (EC) (15.1%), phosphates (63.22%), sulfates (28.5%) and total nitrogen (TN)
      (34.4%), was observed during 15 weeks of operational period. Whereas a
      considerable average increase in the levels of dissolved oxygen (DO) (63.2%) was
      found after treatment of wastewater by the TBF system. No significant reduction
      in most probable number (MPN) index of fecal coliforms was observed in the
      effluent in first 9 weeks of operation. However, a significant reduction in the
      MPN of fecal coliforms was observed, i.e. 80-90% in the last few weeks of
      treatment. Thus, overall results suggest that pilot-scale TBF has a great
      potential to be transferred to field scale for treating sewage for small
      communities in developing countries, in order to produce effluent of good
      quality, which can be safely used for irrigation as well as ornamental purposes.

PMID- 28506118
TI  - Effect of a Diet Enriched with Fresh Coconut Saturated Fats on Plasma Lipids and
      Erythrocyte Fatty Acid Composition in Normal Adults.
AB  - OBJECTIVE: The objective of this study was to compare the effects of increased
      saturated fatty acid (SFA) (provided by fresh coconut) versus monounsaturated
      fatty acid (MUFA) intake (provided by a combination of groundnuts and groundnut
      oil) on plasma lipids and erythrocyte fatty acid (EFA) composition in healthy
      adults. MATERIAL AND METHODS: Fifty-eight healthy volunteers, randomized into 2
      groups, were provided standardized diet along with 100 g fresh coconut or
      groundnuts and groundnut oil combination for 90 days in a Yoga University.
      Fasting blood samples were collected before and after the intervention period for
      the measurement of plasma lipids and EFA profile. RESULTS: Coconut diet increased
      low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels
      significantly. In contrast, the groundnut diet decreased total cholesterol (TC),
      mainly due to a decrease in HDL levels. There were no differences in the major
      SFA of erythrocytes in either group. However, coconut consumption resulted in an
      increase in C14:0 and C24:0 along with a decrease in levels of C18:1 n9 (oleic
      acid). There was a significant increase in levels of C20:3 n6 (dihomo-gamma
      linolenic acid, DGLA). CONCLUSIONS: Consumption of SFA-rich coconut for 3 months
      had no significant deleterious effect on erythrocytes or lipid-related factors
      compared to groundnut consumption. On the contrary, there was an increase in the
      anti-atherogenic HDL levels and anti-inflammatory precursor DGLA in erythrocyte
      lipids. This suggests that coconut consumption may not have any deleterious
      effects on cardiovascular risk in normal subjects.

PMID- 28506120
TI  - Indigenous Peoples of Northern Russia: Anthropology and Health.

PMID- 28506119
TI  - Study of the genetic diversity of the aflatoxin biosynthesis cluster in
      Aspergillus section Flavi using insertion/deletion markers in peanut seeds from
      Georgia, USA.
AB  - Aflatoxins are among the most powerful carcinogens in nature. The major aflatoxin
      producing fungi are Aspergillus flavus and A. parasiticus. Numerous crops,
      including peanut, are susceptible to aflatoxin contamination by these fungi.
      There has been an increased use of RNA interference (RNAi) technology to control
      phytopathogenic fungi in recent years. In order to develop molecular tools
      targeting specific genes of these fungi for the control of aflatoxins, it is
      necessary to obtain their genome sequences. Although high-throughput sequencing
      is readily available, it is still impractical to sequence the genome of every
      isolate. Thus, in this work, the authors proposed a workflow that allowed
      prescreening of 238 Aspergillus section Flavi isolates from peanut seeds from
      Georgia, USA. The aflatoxin biosynthesis cluster (ABC) of the isolates was
      fingerprinted at 25 InDel (insertion/deletion) loci using capillary
      electrophoresis. All isolates were tested for aflatoxins using ultra-high
      performance liquid chromatography. The neighbor-joining, three-dimension (3D)
      principal coordinate, and Structure analyses revealed that the Aspergillus
      isolates sampled consisted of three main groups determined by their capability to
      produce aflatoxins. Group I comprised 10 non-aflatoxigenic A. flavus; Group II
      included A. parasiticus; and Group III included mostly aflatoxigenic A. flavus
      and the three non-aflatoxigenic A. caelatus. Whole genomes of 10 representative
      isolates from different groups were sequenced. Although InDels in Aspergillus
      have been used by other research groups, this is the first time that the cluster
      analysis resulting from fingerprinting was followed by whole-genome sequencing of
      representative isolates. In our study, cluster analysis of ABC sequences
      validated the results obtained with fingerprinting. This shows that InDels used
      here can predict similarities at the genome level. Our results also revealed a
      relationship between groups and their capability to produce aflatoxins. The
      database generated of Aspergillus spp. can be used to select target genes and
      assess the effectiveness of RNAi technology to reduce aflatoxin contamination in
      peanut.

PMID- 28506122
TI  - Examining transitions from youth to adult services for young persons with autism.
AB  - Autism Spectrum Disorder (ASD) presents pervasive challenges for individuals
      throughout their lifetime. Although some financial, community, and individual
      supports are available for children, there are fewer resources available for
      adults with ASD, their families, and/or caregivers. It is important to understand
      the multidimensional shifts associated with the transition from adolescence to
      adulthood for individuals with ASD. To better understand the transitional
      process, a qualitative study comprised 11 semi-structured interviews with
      individuals with ASD and their families. Interviews elicited the experiences of
      individuals and families impacted by ASD as they transition to adulthood and
      adult systems of care. This study found that individuals with ASD and their
      family are exposed to a "lifetime of difficult transitions" due to a limited
      number of service providers and resources including stringent and restrictive
      program and funding criteria. As a result, individuals with ASD and their
      families were concerned about the ability of some individuals with ASD to
      establish meaningful lives in adulthood. These findings challenge existing
      barriers and broader societal values and stigma that impede emerging adults with
      developmental disabilities.

PMID- 28506123
TI  - Jack'd, a Mobile Social Networking Application: A Site of Exclusion Within a Site
      of Inclusion.
AB  - User-generated smartphone applications have created a new level of virtual
      connectivity for gay males, one in which users can create profiles and meet other
      users as nearby or as far away as possible. For those within close proximity, the
      other users can be considered their "virtual neighbors." Although the
      applications are theoretically designed to be places of inclusion and not
      exclusion, where any gay male with economic means can download an application,
      many profiles have been created that exclude other users. Through an examination
      of profiles on one such application, Jack'd, exclusion is found in the way users
      celebrate and reinforce ideas of traditional masculinity and denigrate and
      reinforce stereotypic ideas of femininity embodied by some gay men. Jack'd, and
      other user-generated smartphone applications, can be read as virtual
      neighborhoods where one is excluded based on their gender performance.

PMID- 28506121
TI  - Mammalian Circadian Period, But Not Phase and Amplitude, Is Robust Against Redox
      and Metabolic Perturbations.
AB  - AIMS: Circadian rhythms permeate all levels of biology to temporally regulate
      cell and whole-body physiology, although the cell-autonomous mechanism that
      confers ~24-h periodicity is incompletely understood. Reports describing
      circadian oscillations of over-oxidized peroxiredoxin abundance have suggested
      that redox signaling plays an important role in the timekeeping mechanism. Here,
      we tested the functional contribution that redox state and primary metabolism
      make to mammalian cellular timekeeping. RESULTS: We found a circadian rhythm in
      flux through primary glucose metabolic pathways, indicating rhythmic NAD(P)H
      production. Using pharmacological and genetic perturbations, however, we found
      that timekeeping was insensitive to changes in glycolytic flux, whereas oxidative
      pentose phosphate pathway (PPP) inhibition and other chronic redox stressors
      primarily affected circadian gene expression amplitude, not periodicity. Finally,
      acute changes in redox state decreased PER2 protein stability, phase dependently,
      to alter the subsequent phase of oscillation. INNOVATION: Circadian rhythms in
      primary cellular metabolism and redox state have been proposed to play a role in
      the cellular timekeeping mechanism. We present experimental data testing that
      hypothesis. CONCLUSION: Circadian flux through primary metabolism is cell
      autonomous, driving rhythmic NAD(P)+ redox cofactor turnover and maintaining a
      redox balance that is permissive for circadian gene expression cycles. Redox
      homeostasis and PPP flux, but not glycolysis, are necessary to maintain clock
      amplitude, but neither redox nor glucose metabolism determines circadian period.
      Furthermore, cellular rhythms are sensitive to acute changes in redox balance, at
      least partly through regulation of PER protein. Redox and metabolic state are,
      thus, both inputs and outputs, but not state variables, of cellular circadian
      timekeeping. Antioxid. Redox Signal. 28, 507-520.

PMID- 28506124
TI  - Fluid intelligence: A brief history.
AB  - The concept of fluid and crystallized intelligence was introduced to the
      psychological community approximately 75 years ago by Raymond B. Cattell, and it
      continues to be an area of active research and controversy. The purpose of this
      paper is to provide a brief overview of the origin of the concept, early efforts
      to define intelligence and uses of intelligence tests to address pressing social
      issues, and the ongoing controversies associated with fluid intelligence and the
      structure of intelligence. The putative neuropsychological underpinnings and
      neurological substrates of fluid intelligence are discussed.

PMID- 28506125
TI  - Hemoglobin A1c as a Predictor of Postoperative Infection Following Elective
      Forefoot Surgery.
AB  - BACKGROUND: There remains little evidence to support a perioperative hemoglobin
      A1c (HbA1c) level that could serve as a threshold for a significantly increased
      risk of postoperative surgical site infection (SSI) following forefoot surgery.
      METHODS: A national database was queried for patients who underwent elective
      forefoot surgery with diabetes. Patients with a perioperative HbA1c level within
      3 months of surgery were identified and stratified based on HbA1c level in 0.5
      mg/dL increments. The incidence of SSI was determined by either a diagnosis or
      procedure for SSI within 1 year and a receiver operating characteristic (ROC)
      curve and area under the curve (AUC) analysis was performed to determine an
      optimal threshold value of HbA1c. RESULTS: A total of 4630 patients who underwent
      forefoot surgery with diabetes with a perioperative HbA1c were included. The rate
      of SSI ranged from 2.3% to 11.8%. The inflection point of the ROC curve
      corresponded to an HbA1c level above 7.5 mg/dL ( P < .0001; 95% confidence
      interval [CI] = 0.58-0.67; AUC = 0.631; specificity = 75%; sensitivity = 46%).
      After multivariate analysis, patients with an HbA1c level of 7.5 mg/dL or greater
      had a significantly higher risk for postoperative wound infection compared to
      patients below this threshold (OR = 1.92; 95% CI = 1.5-2.4; P < .0001).
      CONCLUSIONS: The risk of postoperative SSI following forefoot surgery increased
      as the perioperative HbA1c increased. ROC analysis determined that a
      perioperative HbA1c above 7.5 mg/dL could serve as a threshold for a
      significantly increased risk of postoperative SSI following forefoot surgery.
      LEVEL OF EVIDENCE: Level III, comparative series.

PMID- 28506126
TI  - Intergenerational Programs May Be Especially Engaging for Aged Care Residents
      With Cognitive Impairment: Findings From the Avondale Intergenerational Design
      Challenge.
AB  - Intergenerational programs are an authentic way to engage elders in meaningful
      activity and report benefits to both elders and youth. The Avondale
      Intergenerational Design Challenge (AVID) randomly assigned small teams of
      technology students aged 13 to 15 years (total N = 59) to 1 of 24 aged care
      residents with a range of cognitive impairment. Students met with the resident 4
      times over 15 weeks and ultimately crafted a personalized item for them. Students
      showed no change in self-reported attitudes to elders, empathy, or self-esteem
      post-AVID or at 3-month follow-up, compared to a 3-month within-subject control
      period pre-AVID. Compared to usual lifestyle activities, residents showed
      significant improvements in self-reported positive affect and negative affect
      after student visits and were observed to be significantly more engaged during
      visits, especially residents with greater cognitive impairment. The personal and
      guided nature of intergenerational programs may be especially effective in
      engaging elders with cognitive impairment in meaningful activity.

PMID- 28506127
TI  - Living into death: a case for an iterative, fortified and cross-sector approach
      to advance care planning.
AB  - Advance care planning (ACP) has been framed as best practice for quality
      palliative care, yet a growing body of literature affirms the need for an early
      iterative ACP process to begin when people are young and healthy. A significant
      gap appears to exist in the literature regarding the utility of death
      conversations outside the end-of-life context. Could 'death conversations' early
      in life be an effective tool by which doctor and patient can co-construct a more
      healthful way of life, and realistic relationship with death? And what variables
      must be taken into account for these conversations to proceed successfully? This
      paper provides a narrative exploration of the value of death conversations in the
      clinical context in New Zealand. Five exemplars are discussed, drawn from a
      sample of 21 semi-structured interviews with young older adults (54-65 years old)
      not receiving palliative care or diagnosed with a terminal illness. Together,
      these narratives indicate that further community consultation is required to
      determine culturally appropriate ways to initiate productive conversations around
      aging, death and dying and how to build patient/practitioner/family relationships
      which allow these conversations to happen safely. There is a need to acknowledge
      the important factor of culture related to age, generation, sex, faith and
      ethnicity when engaging in conversations about aging, death and dying. By doing
      so, health professionals will be best equipped to assist their patients to live
      well into death.

PMID- 28506128
TI  - A review of curcumin as a biological stain and as a self-visualizing
      pharmaceutical agent.
AB  - Curcumin has been widely used to color textiles but, unlike other natural dyes
      such as hematoxylin or saffron, it rarely has been discussed as a biological
      stain. Aspects of the physicochemistry of curcumin relevant to biological
      staining and self-visualization, i.e., its acidic properties, lipophilicity,
      metal and pseudometal complexes, and optical properties, are summarized briefly
      here. Reports of staining of non-living biological specimens in sections and
      smears, both fixed and unfixed, including specimens embedded in resin, are
      summarized here. Staining of amyloid, boron and chromatin are outlined and
      possible reaction mechanisms discussed. Use of curcumin as a vital stain also is
      described, both in cultured monolayers and in whole organisms. Staining
      mechanisms are considered especially for the selective uptake of curcumin into
      cancer cells. Staining with curcumin labeled nanoparticles is discussed. Toxicity
      and safety issues associated with the dye also are presented.

PMID- 28506129
TI  - Kidney injury in infants and children with iron-deficiency anemia before and
      after iron treatment.
AB  - BACKGROUND: Our study aimed to investigate the effects of iron-deficiency anemia
      (IDA) on renal tubular functions before and after iron treatment for infants and
      children with IDA. We measured urinary levels of two kidney injury markers:
      neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid
      binding protein (L-FABP). MATERIAL AND METHODS: Thirty-six infants and children
      with IDA and 20 matched healthy controls were included. We assessed different
      laboratory parameters, estimated glomerular filtration rate, urinary levels of
      NGAL, and L-FABP. Urinary kidney injury markers were measured in IDA patients
      before and after 3 months of oral iron therapy. RESULTS: IDA patients had
      significantly higher urinary NGAL and L-FABP levels compared to their healthy
      controls. After 3 months of oral iron treatment, there was a significant
      improvement (decrease) in urinary NGAL and L-FABP in infants and children with
      IDA. Urinary markers returned to normal levels (healthy control levels) in
      children with IDA, but not for infants with IDA compared to their healthy
      controls. CONCLUSION: Subclinical kidney injury was found in infants and children
      with IDA. This injury was completely reversible in older children with IDA and
      partially reversible in infants with IDA after iron therapy. Higher urinary
      levels of kidney injury molecules in IDA infants after iron treatment are
      suggestive of more sensitivity of these infants to oxidative stress caused by
      iron therapy or may be due to the immaturity of the kidney and more damage caused
      by IDA which may require more time to recover.

PMID- 28506130
TI  - Fullerenol nanoparticles decrease ischaemia-induced brain injury and oedema
      through inhibition of oxidative damage and aquaporin-1 expression in ischaemic
      stroke.
AB  - BACKGROUND: We examined the possible protective effects of fullerenol
      nanoparticles on brain injuries and oedema in experimental model of ischaemic
      stroke through inhibition of oxidative damage and aquaporin-1 (AQP-1) expression.
      METHODS: Experiment was done in three groups of rats (N = 66): sham, control
      ischaemia and ischaemic treatment. Ischaemia was induced by 90-minutes middle
      cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion. Rats
      received a dose of 10 mg/kg of fullerenol 30 minutes before MCAO. Infarction,
      brain oedema, malondialdehyde (MDA) and nitrate contents as well as mRNA level of
      AQP-1 were determined 24 hours after termination of MCAO. RESULTS: Administration
      of fullerenol before MCAO significantly reduced the infarction of cortex and
      striatum by 72 and 77%, respectively. MCAO induced brain oedema in control
      ischaemic rats (3.83 +/- 0.53%), whereas, fullerenol significantly reduced it
      (0.91 +/- 0.55%). The contents of MDA and nitrate increased in ischaemic
      hemispheres by 86 and 41%, respectively. Fullerenol considerably reduced the MDA
      and nitrate contents by 83 and 48%, respectively. Moreover, MCAO noticeably
      increased the mRNA level of AQP-1 in ischaemic hemispheres by 22%, whereas
      fullerenol significantly decreased it by 29%. DISCUSSION: Fullerenol is able to
      reduce ischaemia-induced brain injuries and oedema possibly through inhibition of
      oxidative damage and AQP-1 expression in ischaemic stroke.

PMID- 28506131
TI  - New drugs and allogeneic hematopoietic stem cell transplantation for
      hematological malignancies: do they have a role in bridging, consolidating or
      conditioning transplantation treatment?
AB  - INTRODUCTION: Novel targeted therapies and monoclonal antibodies can be combined
      with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1)
      before the transplant to reduce tumour burden, 2) as part of the conditioning in
      place of or in addition to conventional agents 3) after the transplant to allow
      long-term disease control. Areas covered: This review focuses on the current
      integration of new drugs with allo-SCT for the treatment of major hematological
      malignancies for which allo-SCT has been a widely-adopted therapy. Expert
      opinion: After having been used as single agent salvage treatments in relapsed
      patients after allo-SCT or in combination with donor lymphocyte infusions, many
      new drugs have also been safely employed before allo-SCT as a bridge to
      transplantation or after it as planned consolidation/maintenance. This era of new
      drugs has opened new important opportunities to 'smartly' combine 'targeted drugs
      and cell therapies' in new treatment paradigms that may lead to higher cure rates
      or longer disease control in patients with hematological malignancies.

PMID- 28506132
TI  - Lanreotide in the management of small bowel angioectasias: seven-year data from a
      tertiary centre.
AB  - BACKGROUND AND AIMS: Haemorrhage from small bowel angioectasias (SBAs) can be
      debilitating to patients who are very often elderly and have multiple
      comorbidities. Our aim was to assess the use of lanreotide in addition to
      endotherapy in patients with SBAs. METHOD: Patients with SBAs on capsule
      endoscopy (CE) who received lanreotide injections from January 2010 to till the
      present day at the Royal Hallamshire Hospital in Sheffield were included.
      Baseline demographics were recorded. Efficacy was evaluated in terms of
      improvement in mean haemoglobin, transfusion requirements and bleeding episodes.
      RESULTS: Twelve patients (67% males, mean age 74 SD +/- 15.5 years) were
      included. All patients had multiple comorbidities. Lanreotide was given at a
      dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week
      interval in 75% of patients and at a six-week interval in 17% of patients. One
      patient (8%) received a single dose. The mean duration of treatment was 19 months
      SD +/- 14.5. Only 17% of patients had their lanreotide stopped due to
      cholelithiasis. There was a significant improvement in mean haemoglobin: 86.8
      versus 98.0 (131-166 g/L, p = .012). The mean number of bleeding episodes (4.18
      versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received
      improved. Patients required less DBEs +/- APCs after starting lanreotide (19
      versus 11 p = .048). CONCLUSION: Lanreotide is a useful adjuvant treatment to
      therapeutic enteroscopy in patients with refractory obscure gastrointestinal
      bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion
      requirements, bleeding episodes and number of DBEs. Overall, it has a good safety
      profile.

PMID- 28506133
TI  - Clinical outcomes following surgically repaired bucket-handle meniscus tears.
AB  - OBJECTIVES: Meniscus tears are one of the most common knee injuries. Our goal is
      to investigate the failure rate for surgically repaired bucket-handle meniscus
      tears and compare clinical outcomes of repairs that failed versus those that did
      not, at a minimum 2-year follow-up interval. METHODS: 51 patients were identified
      in this retrospective cohort study who experienced bucket-handle meniscus tears
      that were isolated or with concomitant ACL injury. Inclusion criteria included
      age range from 13-55 years, confirmed bucket-handle meniscus tear by MRI and
      intraoperatively, and at least two-years of post-operative follow-up following
      index repair. Demographic data and outcome surveys were collected at a minimum of
      two-years follow-up after repair. RESULTS: Of the 51 patients that had a bucket
      handle meniscal repair, 12 (23.5%) were defined as failures (return of symptoms
      alongside re-tear in the same zone of the repaired meniscus within two years of
      surgery). No demographic variables (age, sex, and BMI smoking status, location of
      tear, or concomitant ACL tear) significantly correlated with failure. The mean of
      the Sports and Recreation KOOS was significantly lower between the non-failure
      (87 +/- 14.4) and failure (70 +/- 17.2) cohorts (p = 0.0072). The Quality of Life
      subscale was significantly lower between the non-failure (76 +/- 15.8) and
      failure (57 +/- 18.2) groups (p = 0.0058). There was a significant difference in
      the post-operative Lysholm scores (p = 0.0039) with a mean of 90 +/- 9.1 for the
      entire cohort and means of 92 +/- 8.4 and 83 +/- 8.6, for non-failure and failure
      groups, respectively. CONCLUSIONS: We found a higher failure rate (23.5%) for
      bucket-handle meniscus repairs at two-year follow up than has been cited in the
      literature, which is typically less than 20%, with significantly lower KOOS
      Quality of Life and Sports and Recreation subscales and Lysholm scores for the
      failure cohort. This is the first study to report these outcome scores solely for
      bucket-handle meniscus repairs, shedding light on the post-operative quality of
      life of patients with repair success or failure.

PMID- 28506134
TI  - Efficacy and safety of etanercept in psoriasis and psoriatic arthritis in the
      PRESTA study: analysis in patients from Central and Eastern Europe.
AB  - BACKGROUND: Data are limited on the effectiveness of anti-TNF and other biologics
      on psoriatric arthritis (PsA) in Central and Eastern Europe (CEE). The objective
      of this analysis was to evaluate the efficacy of etanercept (ETN) in PsA patients
      from CEE. METHODS: In PRESTA, patients were randomized to receive ETN 50 mg BIW
      or 50 mg QW for 12 weeks (double-blind phase) and ETN 50 mg QW for 12 additional
      weeks (open label). In this analysis, only patients from Czech Republic, Hungary,
      Poland and Serbia were included. The primary efficacy variable was the proportion
      of subjects achieving a physician global assessment (PGA) of psoriasis status:
      "clear" or "almost clear" at week 12. RESULTS: In the 307 patients, 54% BIW/QW
      compared with 40% (QW/QW) (p = .02), achieved "clear"/"almost clear" for PGA of
      psoriasis at week 12 increasing, to 68% and 60%, respectively (p = .134) by week
      24. Mean improvement from baseline in PASI were 59% versus 49% (p = .005) at week
      6 and 87% versus 81% (p < .05) at week 24, for the BIW/QW and QW/QW groups,
      respectively. ETN was well tolerated in both groups over 24 weeks. CONCLUSIONS:
      Both dose regimens of ETN provided significant improvements in efficacy in PsA
      treatment and were well tolerated.

PMID- 28506135
TI  - Emerging cell cycle inhibitors for acute myeloid leukemia.
AB  - INTRODUCTION: AML therapy remains very challenging despite our increased
      understanding of its molecular heterogeneity. Outcomes with chemotherapy and
      targeted therapy remain poor. Targeting cell cycle regulators might complement
      chemotherapy and targeted therapy and help in improving outcomes. Areas covered:
      Here we cover the pre-clinical and clinical data for both for cyclin dependent
      kinase (CDK) and cell-cycle checkpoint inhibitors. While CDK inhibition can
      inhibit proliferation, checkpoint inhibitors can facilitate cell cycle
      progression in presence of DNA damage and can induce mitotic catastrophe. Expert
      opinion: Though the preclinical data for cell cycle inhibitors in AML is
      compelling, the clinical translation so far has proven to be challenging. This is
      a reflection of the complexity of both, AML and cell cycle regulators. However,
      early introduction of cell-cycle active agents in combination with chemotherapy
      or targeted agents, identifying right sequence of use and identifying right
      biomarkers might pave the way into successful clinical translation.

PMID- 28506136
TI  - Predictors to Intravenous Fluid Responsiveness.
AB  - Management with intravenous fluids can improve cardiac output in some surgical
      patients. Management with static preload indicators, such as central venous
      pressure and pulmonary artery occlusion pressure, has not demonstrated a suitable
      relationship with changes in the cardiac output induced by intravenous fluid
      therapy. Dynamic indicators, such as the variability of arterial pulse pressure
      or stroke volume variation, have demonstrated a suitable relationship. Since
      improvement in cardiac output does not guarantee an adequate perfusion pressure,
      in patients with hypotension, it is also necessary to know whether arterial
      pressure will also increase with intravenous fluid therapy. In this regard, the
      functional assessment of arterial load by dynamic arterial elastance could help
      to determine which patients will improve not only their cardiac output but also
      their mean arterial pressure.

PMID- 28506137
TI  - Elevation of Serum PARK7 and IL-8 Levels Is Associated With Acute Lung Injury in
      Patients With Severe Sepsis/Septic Shock.
AB  - OBJECTIVE: Methods containing only clinical information fail to meet the needs of
      prediction of acute lung injury (ALI) because of the relatively low positive
      predictive value. This study aimed to investigate the feasibility of using
      biomarkers as predictors of ALI in populations with severe sepsis/septic shock
      and to explore difference among biomarkers after adjustment for potential
      confounders. METHODS: Serum specimens were collected from patients with severe
      sepsis/septic shock (n = 172) presented to the emergency department. Patients
      should be ruled out from the study if they were already suffering from ALI or if
      they deteriorated into ALI within 6 hours after specimen collection. The
      development of ALI of the remaining patients was tracked. RESULTS: Of all
      patients with severe sepsis/septic shock who encountered ALI more than 6 hours
      succeeding to specimen collection, 19 deteriorated into ALI. Elevation in serum
      interleukin 8 (IL-8) and Parkinson disease 7 (PARK7) levels had significant
      connection with higher risk of developing ALI ( P = .006; P = .0001). Sepsis
      treatment and vasopressor application led to a robust connection between PARK7
      and succeeding ALI development. Patients who deteriorated into ALI were
      distinguished accurately from patients who avoided ALI using PARK7 or Lung Injury
      Prediction Score (LIPS; area under the receiver operating characteristic curve
      [AUROC], 0.73 and 0.72 for each). Combination of PARK7 and LIPS ameliorated AUROC
      to 0.86 (vs 0.73, P = .05). On the contrary, serum soluble receptor for advanced
      glycation end products and von Willebrand factor made no contribution to the
      prediction of ALI development. CONCLUSIONS: Patients with PARK7 or IL-8 levels
      above normal are more vulnerable to ALI. Patients vulnerable to ALI can be
      distinguished with the combination of serum biomarkers and clinical prediction
      scores. In addition, the early rise in PARK7 emphasizes the importance of
      endothelial injury in the early pathogenesis of ALI.

PMID- 28506138
TI  - Responses to post-graduation surveys do not accurately reflect the workforce.

PMID- 28506139
TI  - Effects of aging and depression on mnemonic discrimination ability.
AB  - Aging and depression have been found to be associated with poorer performance in
      mnemonic discrimination. In the current study, a two-response format mnemonic
      similarity test, Cognitive Drug Research MST, was used to compare these effects.
      Seventy-six participants were tested; with 52 participants in the young group,
      aged 18-35 years, and 24 participants in the elderly group, aged 55 years or
      older. Twenty-two young participants and 10 elderly participants met DSM-IV
      criteria for MDD or dysthymia. Age-related deficits were found for lure
      identification and speed of response. Differences in speed of responses to lure
      images were found for younger depressed participants, and depressive symptom
      severity was found to be negatively associated with lure identification accuracy
      in the elderly. These findings may be viewed as putative behavioral correlates of
      decreased pattern separation ability, which may be indicative of altered
      hippocampal neurogenesis in aging and depression.

PMID- 28506140
TI  - A Multifaceted Hypnosis Smoking-Cessation Program: Enhancing Motivation and Goal
      Attainment.
AB  - Smoking cessation remains a major health priority. Despite public campaigns
      against smoking and widespread availability of smoking-cessation treatments, many
      people continue to smoke. The authors argue that the "problem of motivation,"
      that is, suboptimal or fluctuating motivation to resist smoking urges and to
      comply with the demands of treatment, commonly undermines treatment seeking and
      adherence, appreciably reducing the success rates of smoking-cessation programs.
      The authors describe the history of the Winning Edge smoking-cessation program
      and discuss ways to enhance motivation before, during, and after formal
      treatment. They illustrate how hypnotic suggestions, administered in the context
      of their program, can promote cognitive, behavioral, and emotional commitment to
      treatment and enhance motivation to live a smoke-free life.

PMID- 28506141
TI  - A Pragmatic Guide to the Setting up of Integrated Hypnotherapy Services in
      Primary Care and Clinical Settings.
AB  - Despite the continued debate and lack of a clear consensus about the true nature
      of the hypnotic phenomenon, hypnosis is increasingly being utilized successfully
      in many medical, health, and psychological spheres as a research method,
      motivational tool, and therapeutic modality. Significantly, however, although
      hypnotherapy is widely advertised, advocated, and employed in the private medical
      arena for the management and treatment of many physical and emotional disorders,
      too little appears to be being done to integrate hypnosis into primary care and
      national health medical services. This article discusses some of the reasons for
      the apparent reluctance of medical and scientific health professionals to
      consider incorporating hypnosis into their medical practice, including the
      practical problems inherent in using hypnosis in a medical context and some
      possible solutions.

PMID- 28506142
TI  - The Frustrated and Helpless Healer: Pathways Approaches to Posttraumatic Stress
      Disorders.
AB  - Posttraumatic stress disorder is a psychophysiological disorder, characterized by
      the following: chronic sympathetic nervous activation; persisting
      perceptual/sensory vigilance for threats; recurrent distressing memories of the
      event, including intrusive memories, flashbacks lived as if in the present
      moment, and nightmares; and a persisting negative emotional state including fear
      and shame. The psychophysiological basis for this disorder calls for
      psychophysiologically based interventions. This article presents the case
      narrative of a 29-year-old national guardsman, exposed to combat trauma and later
      to civilian trauma in public safety work. His treatment followed the Pathways
      model, comprised of multimodal interventions, beginning with self-directed
      behavioral changes, then the acquisition of skills (including self-hypnosis), and
      finally professional treatment including clinical hypnosis and EMDR.

PMID- 28506143
TI  - Future-Focused Therapeutic Strategies for Integrative Health.
AB  - For many years, the therapy field was dominated by a focus on the past. In this
      context, many clinicians were trained to use hypnosis as a tool to explore the
      past, and there is a rich literature documenting the use of hypnosis as a tool to
      induce age regression and the uncovering of traumatic memories. This article
      presents a therapeutic paradigm that focuses on the future. Hypnosis is used to
      induce creativity, flexibility, and openness to the future. In the context of
      health care, hypnosis is used to explore the best possible treatment outcome,
      which may be pharmacological, surgical, or a combination of both as well as other
      nonsurgical interventions. This article elaborates on the effective use of a
      therapeutic hypnosis strategy and technique focused on the future.

PMID- 28506145
TI  - Areas of Control Desired by Patients and Families Referred to Hospice Care:
      Perspectives of Hospice Admissions Staff.
AB  - Sense of control in end-of-life (EOL) care plays a critical role in the patient's
      well-being. However, little is known about the areas of control essential to
      patients and families at a specific time point in the illness trajectory: when
      patients stop curative treatments and are referred to hospice. This study
      qualitatively explored such areas. Sixteen admissions staff members from four
      hospice agencies were interviewed about their perceptions of areas in which
      patients and families worried about losing control by accepting hospice. The
      thematic analysis revealed four areas of control: changes to medical care, health
      care provider changes, use of life-sustaining treatments, and daily life.
      Participants of this study put a great emphasis on consistently communicating
      their willingness to honor patients' and families' control over their care
      decisions and lives. Future research should examine control in EOL care among
      diverse populations and effectiveness of hospice staff's strategies to address
      desire for control.

PMID- 28506144
TI  - Hypnosis for Symptom Control in Cancer Patients at the End-of-Life: A Systematic
      Review.
AB  - Hypnosis has been shown to alleviate symptoms and side effects of cancer and its
      treatment. However, less is known about the use of hypnosis at the end of life in
      individuals with cancer. Our goal was to systematically review the literature on
      the use of hypnosis to manage the most common symptoms of end-of-life cancer
      patients: fatigue, sleep disturbances, pain, appetite loss, and dyspnea. EMBASE,
      MEDLINE, COCHRANE, PsychINFO, and SCOPUS databases were searched from inception
      through November 7, 2016. No studies met the inclusion criteria. It appears that
      hypnosis has never been rigorously tested as a means to ameliorate the most
      common symptoms in individuals with cancer at the end of their lives. This
      finding is troubling, as it strongly implies that a population most in need has
      been largely neglected. However, a clear future research direction is revealed
      that may have significant clinical impact.

PMID- 28506146
TI  - The Impact of Shoulder Abduction Loading on Volitional Hand Opening and Grasping
      in Chronic Hemiparetic Stroke.
AB  - BACKGROUND: Up to 60% of individuals with moderate to severe chronic hemiparetic
      stroke experience excessive involuntary wrist/finger flexion that constrains
      functional hand movements including hand opening. It's not known how stroke
      induced brain injury impacts volitional hand opening and grasping forces as a
      result of the expression of abnormal coupling between shoulder abduction and
      wrist/finger flexion or the flexion synergy. OBJECTIVE: The goal of this study is
      to understand how shoulder abduction loading affects volitional hand opening and
      grasping forces in individuals with moderate to severe chronic hemiparetic
      stroke. METHODS: Thirty-six individuals (stroke, 26; control, 10) were recruited
      for this study. Each participant was instructed to perform maximal hand opening
      and grasping forces while the arm was either fully supported or lifted with a
      weight equal to 25% or 50% of the participant's maximal shoulder abduction
      torque. Hand pentagon area, defined as the area formed by the tips of thumb and
      fingers, was calculated during hand opening. Forces were recorded during
      grasping. RESULTS: In individuals with moderate stroke, increasing shoulder
      abduction loading reduced the ability to maximally open the hand. In individuals
      with severe stroke, who were not able to open the hand, grasping forces were
      generated and increased with shoulder abduction loading. Stroke individuals also
      showed a reduced ability to control volitional grasping forces due to the
      enhanced expression of flexion synergy. CONCLUSIONS: Shoulder abduction loading
      reduced the ability to volitionally open the hand and control grasping forces
      after stroke. Neural mechanisms and clinical implications of these findings are
      discussed.

PMID- 28506147
TI  - Long-term Outcome After Survival of a Cardiac Arrest: A Prospective Longitudinal
      Cohort Study.
AB  - BACKGROUND: A cardiac arrest can lead to hypoxic brain injury, which can affect
      all levels of functioning. OBJECTIVE: To investigate 1-year outcome and the
      pattern of recovery after surviving a cardiac arrest. METHODS: This was a
      multicenter, prospective longitudinal cohort study with 1 year of follow-up
      (measurements 2 weeks, 3 months, 1 year). On function level, physical/cardiac
      function (New York Heart Association Classification), cognition (Cognitive Log
      [Cog-log], Cognitive Failures Questionnaire), emotional functioning (Hospital
      Anxiety and Depression Scale, Impact of Event Scale), and fatigue (Fatigue
      Severity Scale) were assessed. In addition, level of activities (Frenchay
      Activities Index, FAI), participation (Community Integration Questionnaire [CIQ]
      and return to work), and quality of life (EuroQol 5D, EuroQol Visual Analogue
      Scale, SF-36, Quality of Life after Brain Injury) were measured. RESULTS: In this
      cohort, 141 cardiac arrest survivors were included. At 1 year, 14 (13%) survivors
      scored below cutoff on the Cog-log. Both anxiety and depression were present in
      16 (15%) survivors, 29 (28%) experienced posttraumatic stress symptoms and 55
      (52%), severe fatigue. Scores on the FAI and the CIQ were, on average,
      respectively 96% and 92% of the prearrest scores. Of those previously working, 41
      (72%) had returned to work. Most recovery of cognitive function and quality of
      life occurred within the first 3 months, with further improvement on some domains
      of quality of life up to 12 months. CONCLUSIONS: Overall, long-term outcome in
      terms of activities, participation, and quality of life after cardiac arrest is
      reassuring. Nevertheless, fatigue is common; problems with cognition and emotions
      occur; and return to work can be at risk.

PMID- 28506148
TI  - Large-Scale Phase Synchrony Reflects Clinical Status After Stroke: An EEG Study.
AB  - BACKGROUND AND PURPOSE: Stroke-induced focal brain lesions often exert remote
      effects via residual neural network activity. Electroencephalographic (EEG)
      techniques can assess neural network modifications after brain damage. Recently,
      EEG phase synchrony analyses have shown associations between the level of large
      scale phase synchrony of brain activity and clinical symptoms; however, few
      reports have assessed such associations in stroke patients. OBJECTIVE: The aim of
      this study was to investigate the clinical relevance of hemispheric phase
      synchrony in stroke patients by calculating its correlation with clinical status.
      METHODS: This cross-sectional study included 19 patients with post-acute ischemic
      stroke admitted for inpatient rehabilitation. Interhemispheric phase synchrony
      indices (IH-PSIs) were computed in 2 frequency bands (alpha [alpha], and beta
      [beta]), and associations between indices and scores of the Functional
      Independence Measure (FIM), the National Institutes of Health Stroke Scale
      (NIHSS), and the Fugl-Meyer Motor Assessment (FMA) were analyzed. For further
      assessments of IH-PSIs, ipsilesional intrahemispheric PSIs (IntraH-PSIs) as well
      as IH- and IntraH-phase lag indices (PLIs) were also evaluated. RESULTS: IH-PSIs
      correlated significantly with FIM scores and NIHSS scores. In contrast, IH-PSIs
      did not correlate with FMA scores. IntraH-PSIs correlate with FIM scores after
      removal of the outlier. The results of analysis with PLIs were consistent with IH
      PSIs. CONCLUSIONS: The PSIs correlated with performance on the activities of
      daily living scale but not with scores on a pure motor impairment scale. These
      results suggest that large-scale phase synchrony represented by IH-PSIs provides
      a novel surrogate marker for clinical status after stroke.

PMID- 28506150
TI  - Chronic Stroke Survivors Improve Reaching Accuracy by Reducing Movement
      Variability at the Trained Movement Speed.
AB  - BACKGROUND: Recovery from stroke is often said to have "plateaued" after 6 to 12
      months. Yet training can still improve performance even in the chronic phase.
      Here we investigate the biomechanics of accuracy improvements during a reaching
      task and test whether they are affected by the speed at which movements are
      practiced. METHOD: We trained 36 chronic stroke survivors (57.5 years, SD +/-
      11.5; 10 females) over 4 consecutive days to improve endpoint accuracy in an arm
      reaching task (420 repetitions/day). Half of the group trained using fast
      movements and the other half slow movements. The trunk was constrained allowing
      only shoulder and elbow movement for task performance. RESULTS: Before training,
      movements were variable, tended to undershoot the target, and terminated in
      contralateral workspace (flexion bias). Both groups improved movement accuracy by
      reducing trial-to-trial variability; however, change in endpoint bias (systematic
      error) was not significant. Improvements were greatest at the trained movement
      speed and generalized to other speeds in the fast training group. Small but
      significant improvements were observed in clinical measures in the fast training
      group. CONCLUSIONS: The reduction in trial-to-trial variability without an
      alteration to endpoint bias suggests that improvements are achieved by better
      control over motor commands within the existing repertoire. Thus, 4 days'
      training allows stroke survivors to improve movements that they can already make.
      Whether new movement patterns can be acquired in the chronic phase will need to
      be tested in longer term studies. We recommend that training needs to be
      performed at slow and fast movement speeds to enhance generalization.

PMID- 28506149
TI  - A Short and Distinct Time Window for Recovery of Arm Motor Control Early After
      Stroke Revealed With a Global Measure of Trajectory Kinematics.
AB  - BACKGROUND: Studies demonstrate that most arm motor recovery occurs within three
      months after stroke, when measured with standard clinical scales. Improvements on
      these measures, however, reflect a combination of recovery in motor control,
      increases in strength, and acquisition of compensatory strategies. OBJECTIVE: To
      isolate and characterize the time course of recovery of arm motor control over
      the first year poststroke. METHODS: Longitudinal study of 18 participants with
      acute ischemic stroke. Motor control was evaluated using a global kinematic
      measure derived from a 2-dimensional reaching task designed to minimize the need
      for antigravity strength and prevent compensation. Arm impairment was evaluated
      with the Fugl-Meyer Assessment of the upper extremity (FMA-UE), activity
      limitation with the Action Research Arm Test (ARAT), and strength with biceps
      dynamometry. Assessments were conducted at: 1.5, 5, 14, 27, and 54 weeks
      poststroke. RESULTS: Motor control in the paretic arm improved up to week 5, with
      no further improvement beyond this time point. In contrast, improvements in the
      FMA-UE, ARAT, and biceps dynamometry continued beyond 5 weeks, with a similar
      magnitude of improvement between weeks 5 and 54 as the one observed between weeks
      1.5 and 5. CONCLUSIONS: Recovery after stroke plateaued much earlier for arm
      motor control, isolated with a global kinematic measure, compared to motor
      function assessed with clinical scales. This dissociation between the time
      courses of kinematic and clinical measures of recovery may be due to the
      contribution of strength improvement to the latter. Novel interventions, focused
      on the first month poststroke, will be required to exploit the narrower window of
      spontaneous recovery for motor control.

PMID- 28506151
TI  - A new primary mobility tool for the visually impaired: A white cane-adaptive
      mobility device hybrid.
AB  - This article describes pilot testing of an adaptive mobility device-hybrid (AMD
      H) combining properties of two primary mobility tools for people who are blind:
      the long cane and adaptive mobility devices (AMDs). The long cane is the primary
      mobility tool used by people who are blind and visually impaired for independent
      and safe mobility and AMDs are adaptive devices that are often lightweight frames
      approximately body width in lateral dimension that are simply pushed forward to
      clear the space in front of a person. The prototype cane built for this study had
      a wing apparatus that could be folded around the shaft of a cane but when
      unfolded, deployed two wheeled wings 25 cm (9.8 in) to each side of the canetip.
      This project explored drop-off and obstacle detection for 6 adults with visual
      impairment using the deployed AMD-H and a standard long cane. The AMD-H improved
      obstacle detection overall, and was most effective for the smallest obstacles (2
      and 6 inch diameter). The AMD-H cut the average drop off threshold from 1.79
      inches (4.55 cm) to .96 inches (2.44 cm). All participants showed a decrease in
      drop off detection threshold and an increase in detection rate (13.9% overall).
      For drop offs of 1 in (2.54 cm) and 3 in (7.62 cm), all participants showed large
      improvements with the AMD-H, ranging from 8.4 to 50%. The larger drop offs of 5
      in (12.7 cm) and 7 in (17.8 cm) were well detected by both types of canes.

PMID- 28506152
TI  - A participatory systems approach to design for safer integrated medicine
      management.
AB  - It is recognised that whole systems approaches are required in the design and
      development of complex health care services. Application of a systems approach
      benefits from the involvement of key stakeholders. However, participation in the
      context of community based health care is particularly challenging due to busy
      and geographically distributed stakeholders. This study used action research to
      investigate what processes and methods were needed to successfully employ a
      participatory systems approach. Three participatory workshops planned and
      facilitated by method experts were held with 30 representative stakeholders.
      Various methods were used with them and evaluated through an audit of workshop
      outputs and a qualitative questionnaire. Findings on the method application and
      participation are presented and methodological challenges are discussed with
      reference to further research. Practitioner Summary: This study provides
      practical insights on how to apply a participatory systems approach to complex
      health care service design. Various template-based methods for systems thinking
      and risk-based thinking were efficiently and effectively applied with
      stakeholders.

PMID- 28506153
TI  - Design and experimental evaluation of yoked hand-clutching for a lever drive
      chair.
AB  - Lever-drive wheelchairs lower physical strain but are less maneuverable than push
      rim wheelchairs. Here, we study a possible solution in which the user
      simultaneously actuates clutches mounted between the levers and wheels each
      stroke via a clutch handle attached to one lever; this solution is of particular
      interest for user groups with only one functional hand. First, to demonstrate
      maneuverability, we show how this "yoked clutch" allows an experienced user to
      maneuver a constrained space. Then, we compared the difficulty of learning a
      yoked clutch chair to a conventional lever-drive transmission (i.e. a one-way
      bearing). Twenty-two unimpaired novice adults navigated a figure-eight track
      during six training sessions over two weeks. Participant mean speed improved
      roughly 60% for both chairs, with similar exponential improvement time constants
      (3 days) and final speeds. However, speed improvement mostly took place overnight
      rather than within the session for hand-clutching, and the physiological cost
      index was also about 40% higher. These results indicate that while hand-clutching
      is no more difficult to learn than a lever-drive, it is reliant on overnight
      improvement. Also, its increased maneuverability comes with decreased efficiency.
      We discuss how the yoked clutch may be particularly well suited for individuals
      with stroke during inpatient rehabilitation.

PMID- 28506155
TI  - Confounding by Symptomatic Mefloquine Exposure in Military Studies of Post
      Traumatic Stress Disorder.

PMID- 28506156
TI  - Flexor Digitorum Superficialis Tendon Sling Volar Plate Reconstruction for Swan
      Neck Deformity in the Spastic Finger.
AB  - The condition of proximal interphalangeal joint (PIPJ) locking in hyperextension
      may occur in the athetoid or spastic hand with moderate or severe swan-neck
      deformity at the 'opening' phase of prehension. The patient's complaints are of
      complete or incomplete locking that may require passive assistance to initiate
      PIPJ flexion. Surgical procedures to overcome this include rerouting the lateral
      band, stabilisation or reconstruction procedure for the volar instability of the
      PIPJ, etc. Volar stabilisation may be achieved by Flexor digitorum superficialis
      (FDS) tenodesis procedures or criss-cross tendon graft for volar plate
      reconstruction. We report a case of successful stabilisation using the criss
      cross tendon sling procedure for volar plate reconstruction using a slip of the
      FDS tendon instead of a free tendon graft. This is a simple and safe procedure
      that effectively corrects the swan-neck deformity and improves the prehension
      function in the hand.

PMID- 28506154
TI  - Seroadaptive Strategies of Vancouver Gay and Bisexual Men in a Treatment as
      Prevention Environment.
AB  - British Columbia's treatment as prevention policy has provided free access to
      highly active antiretroviral therapy (HAART) to all HIV-positive provincial
      residents since 1996. One outcome is an increase in HIV-positive gay and bisexual
      men (GBM) with suppressed viral loads. Previous cross-sectional analyses
      indicated that some Vancouver GBM now recognize condomless anal sex with men on
      HAART who report a suppressed viral load as a seroadaptive strategy. To test the
      hypothesis that this new strategy, termed viral load sorting (VLS), is recognized
      and used among by GBM in the Momentum Health Study, we analyzed longitudinal data
      for HIV-negative/unknown (n = 556) and HIV-positive (n = 218) serostatus
      participants. Analyses indicated that both groups reported VLS, and that
      serostatus and Treatment Optimism Scale scores were significant determinants in
      frequency and use. Results exemplify the medicalization of sex and Rogers'
      Diffusion Of Preventative Innovations Model, and they have important implications
      for HIV research and GBM sexual decision-making.

PMID- 28506158
TI  - Incidence of Carpal Coalition in an Asian Population - Preliminary Findings of a
      Study on Patients from a Distal Radius Fracture Database.
AB  - BACKGROUND: Congenital carpal coalition is usually seen as an incidental finding.
      The incidence of carpal coalition has been reported from 0.1 to 9.5 %; highest
      incidence has been reported in people of African descent. The purpose of our
      study is to evaluate the incidence and subtypes of carpal coalition in an Asian
      population. METHODS: Review of the radiographs of the patients in our distal
      radius fracture database from 2009 to 2014 was conducted to determine the
      incidence and type of carpal coalition. RESULTS: 4141 patients' wrist radiographs
      were reviewed. 2 cases of carpal coalition were identified; this leads to an
      incidence of 0.048%. One was of luno-triquetral type and the other was of capito
      hamate type. CONCLUSIONS: The preliminary results of our study indicate that
      carpal coalition in the Asian population is less common than that reported in the
      Western literature. Our results are inconclusive as to the type of carpal
      coalition that is more common.

PMID- 28506157
TI  - Motor and Sensory Cortical Changes after Contralateral Cervical Seventh Nerve
      Root (CC7) Transfer in Patients with Brachial Plexus Injuries.
AB  - BACKGROUND: Previous animal studies demonstrated that the sensory and motor
      functions in ipsilesional upper limbs that had been reconstructed by CC7 transfer
      eventually associated with the contralesional brain cortices that had originally
      mediated the functions of the ipsilesional upper limbs before brachial plexus
      injury (BPI). Our hypothesis was that the same findings would be seen in humans.
      METHODS: Four patients with total BPI treated with CC7 transfer were included.
      Changes in the locations of the activated areas in the primary motor (M1) and
      somatosensory (S1) cortices corresponding to the motor outputs to and sensory
      inputs from the ipsilesional limbs were investigated using functional near
      infrared spectroscopy (fNIRS) 2-3 years and 6-7 years after surgery. RESULTS: One
      patient was excluded from the evaluation of motor function after CC7 transfer.
      The motor and sensory functions of the ipsilesional upper limb in all patients
      were still controlled by the ipsilesional brain hemisphere 2-3 years after CC7
      transfer. The reconstructed motions of the ipsilesional upper limbs correlated
      with the contralesional M1 in one patient and the bilateral M1s in another
      patient (both of whom demonstrated good motor recovery in the ipsilesional upper
      limbs) and with the ipsilesional M1 in a third patient with poor motor recovery
      in the ipsilesional upper limb. Sensory stimulation of the ipsilesional hands 6-7
      years after CC7 transfer activated the contralesional S1 in two patients who
      achieved good sensory recovery in the ipsilesional hands but activated the
      ipsilesional S1 in the other two patients with poor sensory recovery of the
      ipsilesional hands. CONCLUSIONS: Transhemispheric transposition of the activated
      brain cortices associated with the recovery of motor and sensory functions of the
      ipsilesional upper limbs was seen in patients with CC7 transfer as has been
      reported for animal models of CC7 transfer.

PMID- 28506159
TI  - Progression from Injection to Surgery for Trigger Finger: A Statistical Analysis.
AB  - BACKGROUND: The purpose of this study was to identify predictive factors of poor
      response to intra-flexoral sheath corticosteroid injection, as well as to
      identify factors associated with patients' decisions to undergo surgical
      treatment. METHODS: Data from 112 patients who received steroid injection
      treatment for trigger finger were reviewed retrospectively. Logistic regression
      was used to assess the prognostic value of factors assumed to affect prognosis
      (age, sex, underlying disease, history of illness, presence of carpal tunnel
      syndrome, multiple digit involvement, and pre- and post-operative disability
      scores). RESULTS: Multiple digits were affected in 42 patients. Associated and
      underlying conditions were carpal tunnel syndrome (n = 36), hypertension (n =
      23), hyperlipidemia (n = 14), and history of malignant tumor (n = 10). Logistic
      regression analysis showed that multiple digit involvement and Froimson clinical
      severity score were factors significantly associated with surgical treatment
      after intra-flexoral sheath corticosteroid injection treatment. These two factors
      were also found to be associated with the patients' decisions to undergo surgical
      treatment. CONCLUSIONS: Although local corticosteroid injection is useful in most
      cases, providers need to counsel patients with multiple digit involvement and/or
      severe cases about the possibility of requiring additional surgical treatment.

PMID- 28506160
TI  - The Effect of Psychological Factors on the Outcomes of Carpal Tunnel Release: A
      Systematic Review.
AB  - BACKGROUND: Several studies report that psychological factors are associated with
      outcomes of carpal tunnel release. However, interpretation of the association is
      difficult as there are diverse outcome parameters and patient expectations are
      different. We performed a systematic review to assess the relationships between
      psychological factors and the various outcome parameters. METHODS: We identified
      611 papers and selected 8 papers that fit the inclusion criteria. Psychological
      factors assessed were anxiety, depression, pain catastrophizing, coping, and
      mental health status. Outcomes of interest included satisfaction and measures of
      perceived level of function, pain, and physical measures of recovery. RESULTS:
      For satisfaction and perceived level of function as the outcome, three studies
      reported a significant association, one study found an association approaching a
      value of significance, and one study reported no association. For pain as the
      outcome, two studies reported a significant association. For physical measures,
      one study reported no association. CONCLUSIONS: This systematic review found that
      depression correlates with postoperative pain, but that the association is less
      clear between psychological factors and outcomes such as satisfaction, perceived
      level of symptom and function, and physical measures of recovery. As pain may not
      be a primary symptom or outcome of CTS, we consider that the current literature
      does not strongly support the association between psychological factors and
      outcomes of CTR. This review could be of benefit during preoperative counseling
      in patients with psychological disturbances.

PMID- 28506161
TI  - Symmetric Peripheral Running Sutures are Superior to Asymmetric Peripheral
      Running Sutures for Increasing the Tendon Strength in Flexor Tendon Repair.
AB  - BACKGROUND: The fatigue strength of three peripheral suture techniques for flexor
      tendon repair was compared by cyclic loading of the repairs in the porcine flexor
      digitorum tendon. METHODS: Thirty-six tendons were sutured using only peripheral
      sutures with 6-0 Nylon. An initial cyclic load of 10 N for 500 cycles was applied
      and increased by 10 N for an additional 500 cycles at each new load until
      rupture. RESULTS: The fatigue strength of the symmetric running peripheral suture
      was 85.0% and 144.8% greater than that of the two kinds of the asymmetric running
      peripheral sutures. CONCLUSIONS: Symmetric running sutures can enhance the suture
      strength and appears to be a useful technique for increasing the strength of the
      peripheral suture.

PMID- 28506162
TI  - Brodie's Abscess of the Radius in a Child.
AB  - We herein report an unusual case of Brodie's abscess of the radius in a child. A
      13-year-old boy presented with pain on his right distal forearm. A plain
      radiograph showed an 8 cm translucent lesion in the distal radius. MRI showed a
      penumbra sign on the T1-weighted image, hyperintensity on T2-weighted images, and
      ring enhancement on the contrast-enhanced T1 image. 18F-FDG PET/CT images showed
      an uptake at the margin of the radius. Curettage and iliac cancellous bone
      grafting were undertaken for Brodie's abscess. Bacteriological examinations were
      found to be negative, however, the pathologic diagnosis showed chronic
      osteomyelitis. Eight months after surgery, the patient was asymptomatic and there
      was no sign of recurrence of infection. For Brodie's abscess in a child, thorough
      debridement is mandatory in addition to cancellous bone grafting. Brodie's
      abscess should be considered in the differential diagnosis of a patient who
      presents with forearm pain and exhibit the radiolucent osteolytic lesion on
      simple radiography.

PMID- 28506163
TI  - The Outcome of Treatment of Flexor Sheath (seed) Ganglia by a Percutaneous
      Partial Pulley Release.
AB  - BACKGROUND: The aims of this study were to assess the safety and efficacy of a
      technique of partial percutaneous pulley release. METHODS: A retrospective cohort
      study was undertaken treating adults with seed ganglia with a percutaneous pulley
      release. The patients were reviewed independently after a mean of 6 (range 6-36)
      months. RESULTS: We treated 24 patients over a 3 year period. There were 14 women
      and ten men. The mean age was 39 (range 17-65) years. We were able to assess 21
      patients with long term follow up. There was complete resolution in 14 (2/3) and
      partial resolution in four. The remaining three patients had persisting symptoms
      and requested open surgical excision. Apart from local tenderness and failure of
      resolution there were no complications of percutaneous pulley release.
      CONCLUSIONS: Bursting or aspiration of flexor sheath ganglia appears to be the
      best primary treatment. If the ganglion recurs, this study suggests a
      percutaneous release is safe and will resolve the symptoms in most patients.

PMID- 28506164
TI  - Screw Fixation and Autogenous Bone Graft for an Irreducible Distal Ulna Fracture
      Associated with Distal Radius Fracture.
AB  - Distal ulna fractures often occur with distal radius fractures, and their
      treatment method is still controversial. We considered reduction of the distal
      radio-ulnar joint (DRUJ) surface the most important factor when treating distal
      ulna fractures accompanied by residual dislocation. We herein presented a patient
      with a distal ulna fracture accompanied by dislocation of the DRUJ surface in
      whom an autogenous bone fragment collected from the radius was grafted onto the
      ulnar bone defect after open reduction and Herbert screw fixation. In this
      technique, the bone fragment was supported through the medullary cavity by
      inserting a Herbert screw, which was less likely to cause irritation between the
      screw and surrounding tissue, because the screw was almost entirely present in
      the bone. In addition, an autogenous bone graft from the same surgical field may
      be less invasive than that from another region.

PMID- 28506165
TI  - Cold Welding in a Trapeziometacarpal Ball and Socket Prosthesis: A Case Report.
AB  - While in revision hip surgery it has been described cold welding of the femoral
      component in titanium implants, no previous reports have been published in TMC
      prosthesis. We present a case report of a patient who sustained a TMC ARPE(r)
      dislocation 11 months after surgery and during revision surgery, cold welding of
      the neck with the metacarpal stem was observed. This may represent a problem when
      revising this prosthesis and alternative procedures should be advised and
      discussed with the patient when revising these implants.

PMID- 28506166
TI  - Pacinian Corpuscles Neuroma. An Exceptional Cause of Pain in the Hand.
AB  - Pacinian corpuscles are rapidly adapting mechanoreceptors mainly distributed in
      the dermis of the fingers and palm of the hand. A neuroma of the Pacinian
      corpuscle is a rare and extremely painful condition with a few cases reported in
      the literature, most of them, associated with local or repetitive trauma. We
      present a 71-year-old man with history of pain and swelling on his left index
      without history of previous trauma initially diagnosed as tenosynovitis resistant
      to conservative treatment in which we observed, directly in the subcutaneous
      plane, spherical, gray and in clusters lesions closer to the collateral nerve
      which were described by the pathological study as neuroma of the Pacinian
      corpuscles.

PMID- 28506167
TI  - Two-dimensional Morphological Characteristics of the Distal Radius on Axial
      Magnetic Resonance Image and the Effects on Distal Screw Length.
AB  - BACKGROUND: Detection of dorsal cortical penetration of distal locking screws is
      difficult owing to the irregular shape of the dorsal surface of the distal
      radius. This study was designed to analyze two-dimensional morphological
      characteristics of the distal radius on axial magnetic resonance image, and to
      suggest a guideline for evaluation of screw length in distal radius fractures on
      the fluoroscopic or plain X-ray true lateral image. METHODS: Anteroposterior
      length and lateral width of the distal radius, distance between the highest and
      the lowest point of the dorsal cortex (deceptive length), and widths of the first
      to second (hazard zone) and the third to fifth extensor compartments (safe zone)
      at the Lister tubercle level were measured on 104 axial magnetic resonance images
      by two hand surgeons. RESULTS: The mean length and width of the distal radius at
      the Lister tubercle level were 22.96 mm and 30.42 mm, respectively. The mean
      hazard zone and safe zone widths were 8.72 mm and 19.43 mm, respectively. The
      mean deceptive length was 4.07 mm and the deceptive length did not have a
      relationship with height, sex, and age of subjects. CONCLUSIONS: We suggest that
      4 mm be used as a reference value for the evaluation screw length at the safe
      zone. If the vertical distance between a distal screw tip and the peak of the
      Lister tubercle is lesser than 4 mm on a fluoroscopic or plain X-ray true lateral
      image, dorsal cortical penetration should be suspected. When dorsal cortical
      penetration at the hazard zone is suspected, both oblique or pro-supination views
      should be checked.

PMID- 28506168
TI  - Trigger Finger: An Atraumatic Medical Phenomenon.
AB  - Trigger finger is a mechanical problem with many etiological factors as possible
      causes, such as diabetes mellitus, carpal tunnel syndrome and repetitive finger
      movements. Although it can afflict anyone, it is much commoner in middle-aged
      women than men and the most commonly involved digit is reported to be the thumb.
      The diagnosis is mainly based on clinical symptoms during examination and first
      line treatment is conservative with splinting and corticosteroid injections.
      Surgical open release is the "gold standard" of trigger finger treatment because
      it allows more careful inspection of the surgical area and is highly effective
      with low complication rates.

PMID- 28506169
TI  - Painful Snapping of Thumb Caused by Osteochondroma of Trapezium.
AB  - Osteochondroma is the most common benign bone tumor. Lesions occurring at the
      carpal bones are extremely rare. There are very few cases of osteochondroma at
      the trapezium had been reported in the English literature. We reported a 47-year
      old patient with an osteochondroma of the left trapezium presented with painful
      snapping of abductor pollicis longus tendon.

PMID- 28506170
TI  - Osteoid Osteoma of the Distal Phalanx of the Ring Finger with Clubbed Finger
      Deformity: A Case Report.
AB  - Osteoid osteoma of the distal phalanx is very rare. We describe a case of osteoid
      osteoma of the distal phalanx of the ring finger with clubbed finger deformity
      that improved after tumour removal. A 50-year-old left-handed man presented with
      a history of right ring finger pain without any trauma. The distal phalanx of the
      ring finger had tender, redness, and a clubbed finger deformity. Plain
      radiography indicated a circular radiolucent area in the centre of the lesion.
      Computed tomography and gadolinium enhanced magnetic resonance imaging indicated
      presence of a nidus. The lesion was removed via the transungual approach.
      Histopathological examination confirmed the presence of an osteoid osteoma. His
      pain was immediately relieved after surgery. At the 2-year followup, he had no
      pain and the clubbed finger deformity had improved. In cases where clubbed finger
      deformity involves only one finger, the possibility of chronic osteomyelitis or
      osteoid osteoma should be considered.

PMID- 28506171
TI  - A Protocol for Evaluation and Rehabilitation of Distal Radius Fractures Using
      Sensorimotor Input: A Case Series.
AB  - BACKGROUND: Proprioception and sensorimotor input are used to treat neurological
      and joint injuries. Following distal radius fractures (DRF) there is a temporary
      loss of proprioception that should be addressed. We created a protocol for
      evaluation, and a treatment plan following wrist surgery that is based on
      proprioceptive and sensorimotor input. We describe a series of patients
      undergoing surgery for DRF that were evaluated and treated with these protocols.
      METHODS: Both evaluation and treatment protocols included comprehensive
      sensorimotor procedures performed with eyes open and closed. These included
      Semmes- Weinstein, static and moving 2-point discrimination, vibration,
      temperature testing, Moberg pick-up- test, stereognosis and proprioception.
      RESULTS: A series of twelve patients was evaluated and treated with the protocol
      following surgical treatment for DRF. Patients demonstrated significant
      sensorimotor deficits, which improved utilizing the comprehensive sensorimotor
      treatment protocol. CONCLUSIONS: Further study is necessary to validate the
      results of this pilot series. Use of proprioception and sensorimotor input may
      improve outcomes of rehabilitation following DRF.

PMID- 28506172
TI  - The Effect of Myostatin (GDF-8) on Proliferation and Tenocyte Differentiation of
      Rat Bone Marrow-Derived Mesenchymal Stem Cells.
AB  - BACKGROUND: The future in flexor tendon surgery involves tissue engineering
      approaches directed toward increasing early repair strength to accelerate tendon
      healing and to allow for earlier onset of rehabilitation. Previous work has shown
      that pluripotential mesenchymal stem cells may be successfully delivered to a
      tendon repair site using a suture carrier. The current work describes the use of
      Myostatin (GDF-8) to help guide these delivered pluripotential stem cells to
      differentiate down a tenocyte lineage to potentially maximize the reparative
      effects of these cells at the tendon repair site. METHODS: Primary rat bone
      marrow mesenchymal stem cells isolated from the long bones of male Sprague-Dawley
      rats were treated with 500 ng/ml myostatin for 24 h, 48 h, and 72 h. Collagen 1
      A, scleraxis (Scx), and tenomodulin (Tnmd) expression, indicative of tenogenesis,
      was analyzed using real time PCR and immunohistochemistry staining. A migration
      assay was performed to assess the functional activity of BMSCs after they were
      treated with myostatin. RESULTS: Compared to the control cells (without
      treatment), the cells treated with 500 ng/ml myostatin for 72 h exhibited higher
      expression of Col 1A, Scx, and Tnmd. The mRNA expression of Col1A, Scx, Tnmd
      increased 15.3, 13 and 7 times respectively. Immunohistochemistry staining showed
      Scx and Tnmd were expressed in the cellular cytoplasm. In response to myostatin,
      the cells also showed a tendency to proliferate and migrate more than the control
      cells. CONCLUSIONS: Myostatin (GDF-8) has the ability to increase rat bone marrow
      mesenchymal stem cell growth and differentiation toward a tenocyte lineage. This
      information could be useful for future studies regarding tendon repair.

PMID- 28506173
TI  - That Tendon is the Median Nerve: Perils of a Palmaris Longus Deficient Wrist.
AB  - BACKGROUND: To document the course of the median nerve in the distal forearm in
      palmaris longus (PL) deficient forearms and elucidate features that help
      distinguish it from the PL. METHODS: In the cadaveric study, 56 cadaveric
      forearms were dissected and the location and course of the median nerve were
      documented. In the clinical study, 20 healthy subjects with absent PL were
      examined with provocative tests to elucidate the PL (Schaeffer's test and
      Thompson's test), and modified Durkan's and Phalen's tests. In the imaging study,
      one subject with a clearly visible and palpable median nerve was further
      evaluated with MRI with a superficial fiducial marker. RESULTS: Cadaveric
      dissection revealed that the median nerve was deep to the antebrachial fascia and
      superficial to the FDS tendons in the distal forearm. In 9 specimens without a
      PL, the median nerve was the most superficial structure deep and lay draped over
      the FDS tendons. In the clinical study, PL absence was bilateral in 4 subjects
      and unilateral in 16. The nerve was visible and palpable in 4 forearms and
      palpable but not visible in 20 forearms. In all 24 forearms, the nerve was
      palpable as a lax, mobile, cord-like structure that could be rolled over the taut
      FDS tendons. Tinel's and Durkan's signs were positive in 11 subjects. In the
      imaging study, MRI confirmed that the palpable structure was the median nerve.
      CONCLUSIONS: Unlike the PL, the nerve is non-contractile and remains flaccid on
      provocative testing. It is usually palpable and may also be visible in thin
      forearms. Careful scrutiny may reveal it to be distinct from, and draped over
      underlying FDS tendons. These findings may help avoid inadvertent median nerve
      harvest in place of a PL tendon graft.

PMID- 28506174
TI  - X-ray Guided Steroid Injections for Proximal Interphalangeal Joint Osteoarthritis
      of the Fingers.
AB  - BACKGROUND: Osteoarthritis of the finger proximal interphalangeal joints (PIPJ's)
      is common and severely limits hand function. Intra-articular steroid injections
      are frequently used, but there is little research assessing this treatment
      option. METHODS: This was a prospective audit of patients undergoing intra
      articular steroid injections into the PIPJ under image intensifier guidance. The
      aims were to assess the duration of pain relief, hand function and range of
      movement following this procedure. Fifty injected joints were followed up at six
      weeks, three and six months. RESULTS: There were significant improvements in both
      pain scores and the range of movement for up to three months. Analgesia
      requirements decreased and hand function improved up to three months. By six
      months, patients were approaching their preinjection scores. CONCLUSIONS: X-ray
      guided injections are a simple procedure which can be effectively performed in
      the out- patient setting, resulting in satisfied patients with improved hand
      function and pain scores.

PMID- 28506175
TI  - Corrective Step-cut Osteotomy at the Affected Bone for Correction of Rotational
      Deformity Due to Fracture of the Middle Phalanx.
AB  - Malunion at the shaft of the middle phalanx yields less functional problems
      compared with malunion at the shaft of the proximal phalanx and metacarpal bones.
      In the present report, the patient sustained a minimally displaced fracture at
      the distal portion of the distal middle phalanx of the ring finger spraining the
      finger during playing flag football. Fracture was treated conservatively and
      fracture union was completed. However, the patient complained of functional
      problems in activities of daily living due to the malrotational deformity of the
      finger. We treated the malrotational deformity close to the distal
      interphalangeal joint of the middle phalanx with step-cut osteotomy at the
      affected bone successfully.

PMID- 28506176
TI  - Neurolysis with Amniotic Membrane Nerve Wrapping for Treatment of Secondary
      Wartenberg Syndrome: A Preliminary Report.
AB  - BACKGROUND: Entrapment of the superficial sensory branch of the radial nerve
      (SRN) commonly results in debilitating pain of the dorsoradial wrist. Symptom
      relief following SRN neurolysis is often incomplete or temporary due to recurrent
      perineural scarring. METHODS: We performed a retrospective review with
      prospective follow-up of all patients with SRN neuropathy who were treated with
      neurolysis and nerve wrapping using an amnion-based allograft adhesion barrier
      over a one-year interval. Measured outcomes included pain rated by Visual Analog
      Scale (VAS) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH)
      functional outcome scores. RESULTS: Three females satisfied inclusion. At mean
      follow-up of 28.9 months, all three patients exhibited improved pain (mean VAS
      change -4.7 +/- 0.6), function (mean QuickDASH change -40 +/- 5), and subjective
      satisfaction. No adverse events or reactions to the implanted tissue occurred.
      CONCLUSIONS: SRN entrapment neuropathy was safely and effectively treated with
      neurolysis and amnion nerve wrapping in this small series. Use of this technique
      for perineural scar prevention warrants additional study in larger groups of
      patients and in other upper extremity entrapment neuropathies.

PMID- 28506177
TI  - Metastasis of Renal Cell Carcinoma to the Trapezium.
AB  - Solitary metastasis of a carcinoma to carpal bone is extremely rare. Metastases
      of renal cell carcinoma (RCC) usually occur in a multiple fashion and there has
      been no report to date of a solitary metastasis to trapezium from RCC. The tumor
      was excised and reconstructed with iliac bone transplantation. 2 years and 6
      months after surgery, there is no local recurrence with minimal functional loss.

PMID- 28506178
TI  - Galeazzi-equivalent Fractures: Report of Two Cases and Literature Review.
AB  - The Galeazzi-equivalent fracture is a rare injury that occurs in children. The
      most important issue is the distal ulnar epiphyseal injury. Although there have
      been some case reports, most of them performed only short term follow-up. This
      article describes two cases of this fracture with long term follow-up until
      epiphyseal closure. First case is a 12-year-old girl who sustained a
      Galeazziequivalent fracture of her right forearm and underwent emergency surgery.
      At follow-up of 5 years and 10 months postsurgery, radiographs show ulnar growth
      arrest of one mm and she has mild pain. Second case is a 15-year-old boy who
      sustained an open Galeazzi-equivalent fracture of his left forearm and underwent
      emergency surgery. At follow-up of 3 years and 3 months postsurgery, radiographs
      show no growth arrest of the distal ulna. He has no residual complaint. Long term
      follow-up is absolutely necessary to monitor ulnar growth.

PMID- 28506179
TI  - Value of Soft Tissue Release Procedure around the Shoulder to Improve Shoulder
      Abduction in Birth Brachial Plexus Palsy and Analysis of the Factors Affecting
      Outcome.
AB  - BACKGROUND: A lack of shoulder abduction in spontaneously recovered birth
      brachial plexus palsy (BBPP) is a common presentation. We have performed a soft
      tissue release operation in these patients to remove the tethering effect of the
      tight and cocontracting shoulder adductors. This study was undertaken in order to
      assess the outcome of this surgical procedure. METHODS: We performed a
      retrospective analysis of 120 patients who displayed spontaneous recovery from
      BBPP and subsequently underwent soft tissue release procedure to improve shoulder
      abduction. The operation involved release of the pectoralis major, latissimus
      dorsi (LD) and teres major (TM) with axillary nerve neurolysis and transfer of LD
      and TM to teres minor at a lower position. Outcomes were assessed at a minimum
      follow up of two years. The primary outcome measures were range of shoulder
      abduction and Mallet score. Parents were interviewed and their satisfaction was
      graded on a Likert scale. We also explored prognostic factors responsible for
      better outcomes namely, age at operation, extent of involvement; preoperative
      shoulder abduction range, internal rotation deformity, triceps power and Mallet
      score. RESULTS: The average patient age was 5.8 years(range 1-17). Follow up
      ranged from 2-6 years. Average preoperative shoulder abduction was 85 degrees 
      (range 30 degrees -140 degrees ). Postoperatively the average shoulder abduction
      was 161 degrees  (range 80 degrees -180 degrees ). The mean improvement in
      abduction was 76 degrees  (range 20 degrees -110 degrees ) [p < 0.001]. Mallet
      score improved from 16.4 to 19.5 (p < 0.001). High parental satisfaction was
      recorded by Likert scale assessment. Regression analysis indicated a favourable
      outcome in patients who are younger, have a better preoperative abduction range
      and a preoperative triceps power > grade 3. CONCLUSIONS: Soft tissue release
      procedure employed in this series is effective in improving shoulder abduction.
      Patients who are of younger age, have better preoperative abduction and triceps
      power of > grade 3 are expected to achieve the best outcome.

PMID- 28506180
TI  - Midterm Follow-up of Treating Volar Marginal Rim Fractures with Variable Angle
      Lcp Volar Rim Distal Radius Plates.
AB  - BACKGROUND: Specific treatment of the volar marginal rim fragment of distal
      radius fractures avoids occurance of volar radiocarpal dislocation. Although
      several fixation systems are available to capture this fragment, adequately
      maintaining internal fixation is difficult. We present our experience of the
      first 10 cases using the 2.4 mm variable angle LCP volar rim distal radius plate
      (Depuy Synthes(r), West Chester, US), a low-profile volar rim-contouring plate
      designed for distal plate positioning and stable buttressing of the volar
      marginal fragment. METHODS: Follow-up patient satisfaction, range of motion,
      grips strength, functional scoring with the QuickDASH and residual pain with a
      numeric rating scale were assessed. Radiological evaluation consisted in
      evaluating fracture consolidation, ulnar variance, volar angulation and
      maintenance of the volar rim fixation. RESULTS: The female to male ratio was 5:5
      and the mean age was 52.2 (range, 17-80) years. The mean follow-up period was 11
      (range, 5-19) months postoperatively. Patient satisfaction was high. The mean
      total flexion/extension range was 144 degrees  (range, 100-180 degrees ) compared
      to the contralateral uninjured side 160 degrees  (range, 95-180 degrees ). The
      mean total pronation/supination range was 153 degrees  (range, 140-180 degrees )
      compared to the contralateral uninjured side 170 degrees  (range, 155-180 degrees
      ). Mean grip strength was 14 kg (range, 9-22), compared to the contralateral
      uninjured side 20 kg (range, 12-25 kg). Mean pre-injury level activity QuickDASH
      was 23 (range, 0-34.1), while post-recovery QuickDASH was 25 (range 0-43.2).
      Residual pain was 1.5 on the visual numerical pain rating scale. Radiological
      evaluation revealed in all cases fracture consolidation, satisfactory
      reconstruction of ulnar variance, volar angulation and volar rim. We encountered
      no flexor tendon complications, although plate removal was systematically
      performed after fracture consolidation. CONCLUSIONS: The 2.4 mm variable angle
      LCP volar rim distal radius plates is a valid treatment option for treating the
      volar marginal fragment in distal radius fractures.

PMID- 28506181
TI  - Intersectionality in the Lives of LGBTQ Youth: Identifying as LGBTQ and Finding
      Community in Small Cities and Rural Towns.
AB  - This article presents an analysis of the views of younger bisexual and lesbian
      women and transgender youth living in a western Canadian small city on their
      sexual and gender identities. Data were collected through focus groups and
      interviews and analyzed thematically through an intersectional lens. The
      purposive sample was composed of 13 youth who identified as lesbian, gay,
      bisexual, transgender, or queer (LGBTQ) and whose average age was 19.8 years. The
      analytical themes of (1) living in a small town, (2) identifying and being
      identified, and (3) talking intersectionality indicate that the sexual identities
      and gender identities and expressions of LGBTQ youth change across time and
      context and are impacted by often overlooked factors including faith, Indigenous
      ancestry, disability, and class. Further, the size and character of the community
      significantly impacts LGBTQ youth identity development and expression. This
      research demonstrates the uniqueness of individual youth's experiences-opposing
      notions of milestone events as singularly important in queer youth identity
      development.

PMID- 28506182
TI  - Elemental properties of copper slag and measured airborne exposures at a copper
      slag processing facility.
AB  - In 1974, the National Institute for Occupational Safety and Health recommended a
      ban on the use of abrasives containing >1% silica, giving rise to abrasive
      substitutes like copper slag. We present results from a National Institute for
      Occupational Safety and Health industrial hygiene survey at a copper slag
      processing facility that consisted of the collection of bulk samples for metals
      and silica; and full-shift area and personal air samples for dust, metals, and
      respirable silica. Carcinogens, suspect carcinogens, and other toxic elements
      were detected in all bulk samples, and area and personal air samples. Area air
      samples identified several areas with elevated levels of inhalable and respirable
      dust, and respirable silica: quality control check area (236 mg/m3 inhalable;
      10.3 mg/m3 respirable; 0.430 mg/m3 silica), inside the screen house (109 mg/m3
      inhalable; 13.8 mg/m3 respirable; 0.686 mg/m3 silica), under the conveyor belt
      leading to the screen house (19.8 mg/m3 inhalable), and inside a conveyor access
      shack (11.4 mg/m3 inhalable; 1.74 mg/m3 respirable; 0.067 mg/m3 silica). Overall,
      personal dust samples were lower than area dust samples and did not exceed
      published occupational exposure limits. Silica samples collected from a plant
      hand and a laborer exceeded the American Conference of Governmental Industrial
      Hygienist Threshold Limit Value of 0.025 ug/m3. All workers involved in copper
      slag processing (n = 5) approached or exceeded the Occupational Safety and Health
      Administration permissible exposure limit of 10 ug/m3 for arsenic (range: 9.12
      18.0 ug/m3). Personal total dust levels were moderately correlated with personal
      arsenic levels (Rs = 0.70) and personal respirable dust levels were strongly
      correlated with respirable silica levels (Rs = 0.89). We identified multiple
      areas with elevated levels of dust, respirable silica, and metals that may have
      implications for personal exposure at other facilities if preventive measures are
      not taken. To our knowledge, this is the first attempt to characterize exposures
      associated with copper slag processing. More in-depth air monitoring and health
      surveillance is needed to understand occupational exposures and health outcomes
      in this industry.

PMID- 28506183
TI  - Strategies and challenges for communicating the diagnosis of cancer in cross
      cultural clinical settings-Perspectives from South African healthcare
      professionals.
AB  - Communicating the diagnosis of cancer in cross-cultural clinical settings is a
      complex task. This qualitative research article describes the content and process
      of informing Zulu patients in South Africa of the diagnosis of cancer, using
      osteosarcoma as the index diagnosis. We used a descriptive research design with
      census sampling and focus group interviews. We used an iterative thematic data
      analysis process and Guba's model of trustworthiness to ensure scientific rigor.
      Our results reinforced the use of well-accepted strategies for communicating the
      diagnosis of cancer. In addition, new strategies emerged which may be useful in
      other cross-cultural settings. These strategies included using the stages of
      cancer to explain the disease and its progression and instilling hope using a
      multidisciplinary team care model. We identified several patients, professionals,
      and organizational factors that complicate cross-cultural communication. We
      conclude by recommending the development of protocols for communication in these
      cross-cultural clinical settings.

PMID- 28506184
TI  - Complications of Psychotropic and Pain Medications in an Ultrarapid Metabolizer
      Patient at the Upper 1% of Cytochrome P450 (CYP450) Function Quantified by
      Combinatorial CYP450 Genotyping.
AB  - A 44-year-old Caucasian woman presented with a history of empirical treatment
      with 20 pain and psychotropic medications, as well as dual comorbidity of
      intractable pain and depression. A multiple gain-of-function profile in the
      CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was
      discovered. The patient was a homozygote of suprafunctional alleles for both
      CYP2D6 (*35/*35) and CYP2C19 (*17/*17) genes and functional alleles for CYP2C9
      (*1/*1), which account for aggregate drug metabolism function at the upper 1% of
      the population. The patient improved clinically with discontinuation of
      psychotropics and pain medications that were substrates of CYP2D6 and/or CYP2C19,
      suggesting that much of her symptomatology was drug induced. Combinatorial
      genotyping of CYP450 genes is diagnostically useful in individuals with histories
      of multiple side effects or drug resistance, which could be avoided by
      genetically informed therapeutics in behavioral health.

PMID- 28506185
TI  - The cascading influence of multisensory processing on speech perception in
      autism.
AB  - It has been recently theorized that atypical sensory processing in autism relates
      to difficulties in social communication. Through a series of tasks concurrently
      assessing multisensory temporal processes, multisensory integration and speech
      perception in 76 children with and without autism, we provide the first
      behavioral evidence of such a link. Temporal processing abilities in children
      with autism contributed to impairments in speech perception. This relationship
      was significantly mediated by their abilities to integrate social information
      across auditory and visual modalities. These data describe the cascading impact
      of sensory abilities in autism, whereby temporal processing impacts multisensory
      information of social information, which, in turn, contributes to deficits in
      speech perception. These relationships were found to be specific to autism,
      specific to multisensory but not unisensory integration, and specific to the
      processing of social information.

PMID- 28506186
TI  - Response to Letter to the Editor: Confounding by Symptomatic Mefloquine Exposure
      in Military Studies of Post-Traumatic Stress Disorder.

PMID- 28506188
TI  - Corrigendum.

PMID- 28506187
TI  - Ten-Year Changes in Healthy Eating Attitudes in the SUN Cohort.
AB  - OBJECTIVE: The objective of this study was to assess the within-subject
      longitudinal changes in self-perceived healthy eating attitudes after 10 years of
      follow-up and to identify predictors of long-term changes in a middle-aged adult
      cohort. METHODS: Four thousand five hundred seventy-two participants completed a
      validated food frequency questionnaire (FFQ) at baseline and after 10 years of
      follow-up. The FFQ was expanded with a brief 10-item questionnaire about eating
      attitudes with 2 possible answers: yes or no. A baseline score and a 10-year
      score were calculated with these 10 items (range from 0 to 10). Participants were
      categorized into 3 groups according to this score. Linear and logistic
      regressions were used to examine changes at follow-up and associations between
      baseline characteristics and improvement in the score. RESULTS: After 10 years of
      follow-up, a statistically significant favorable change (p < 0.001) was achieved
      in all questions about eating attitudes, particularly in these items: "Do you try
      to eat less sweets and pastries?" (12%), "Do you try to eat less meat?" (11.1%),
      and "Do you try to reduce your fat intake?" (10%). Being female (odds ratio [OR]
      = 1.19, 95% confidence interval [CI], 1.02-1.39), being 35-50 or >= 50 years old
      (OR = 1.24, 95% CI, 1.07-1.44 and OR = 1.74, 95% CI, 1.38-2.18, respectively), a
      high level of physical activity (OR for third vs first tertile = 1.20, 95% CI,
      1.02-1.41), and a higher Mediterranean diet score (OR for second and third
      tertiles = 1.18, 95% CI, 1.01-1.37 and OR = 1.26, 95% CI, 1.04-1.52,
      respectively) were associated with a higher probability of improving the eating
      attitudes score, while a low body mass index (BMI; OR = 0.71, 95% CI, 0.51-1.00)
      and snacking between meals (OR = 0.84, 95% CI, 0.73-0.97) were associated with a
      lower probability of improving their score. CONCLUSIONS: The eating attitudes of
      the participants in the Seguimiento Universidad de Navarra (SUN) cohort became
      more favorable after 10 years of follow-up. Certain sociodemographic or clinical
      variables may predict a positive change.

PMID- 28506190
TI  - Comparison of Blood Glucose Monitoring Systems for Use in Insulin Clamp Studies
      During Either Intralipid or Glycerol Co-infusions.

PMID- 28506189
TI  - Conducting Biobehavioral Research in Patients With Advanced Cancer: Recruitment
      Challenges and Solutions.
AB  - Despite significant advances in cancer treatment and symptom management
      interventions over the last decade, patients continue to struggle with cancer
      related symptoms. Adequate baseline and longitudinal data are crucial for
      designing interventions to improve patient quality of life and reduce symptom
      burden; however, recruitment of patients with advanced cancer in longitudinal
      research is difficult. Our purpose is to describe challenges and solutions to
      recruitment of patients with advanced cancer in two biobehavioral research
      studies examining cancer-related symptoms. Study 1: Symptom data and peripheral
      blood for markers of inflammation were collected from newly diagnosed patients
      receiving chemotherapy on the first day of therapy and every 3-4 weeks for up to
      6 months. Study 2: Symptom data, blood, and skin biopsies were collected from
      cancer patients taking epidermal growth factor receptor inhibitors at specific
      time points over 4 months. Screening and recruitment results for both studies are
      summarized. Timing informed consent with baseline data collection prior to
      treatment initiation was a significant recruitment challenge for both the
      studies. Possible solutions include tailoring recruitment to fit clinic needs,
      increasing research staff availability during clinic hours, and adding
      recruitment sites. Identifying solutions to these challenges will permit the
      conduct of studies that may lead to identification of factors contributing to
      variability in symptoms and development of tailored patient interventions for
      patients with advanced cancer.

PMID- 28506191
TI  - Use of the Neuropsychiatric Inventory to Characterize the Course of
      Neuropsychiatric Symptoms in Progressive Supranuclear Palsy.
AB  - The aim of this study was to determine the neuropsychiatric profile in a cohort
      of progressive supranucelar palsy (PSP) patients and their dynamic changes over a
      follow-up period of 1 year. A total of 59 patients were assessed at baseline,
      while 25 of them were accessible after 1 year of the follow-up. The most common
      symptoms were apathy and depression, which were also found to be, among other
      variables, the independent determinants of increased Neuropsychiatric Inventory
      (NPI) total score. Moreover, apathy deteriorated most profoundly over the follow
      up period. The NPI seemed to be a sensitive measure of behavioral changes in PSP.

PMID- 28506192
TI  - The Expanding Prominence of Toxic Leukoencephalopathy.
AB  - Toxic leukoencephalopathy (TL) is a disorder of brain white matter caused by
      exposure to leukotoxic agents. Magnetic resonance imaging (MRI) can readily
      identify this syndrome, and, together with diffusion tensor imaging, MRI
      continues to offer important insights into its nature. Since the first formal
      description of TL in 2001, many new leukotoxic disorders have been recognized,
      and the range of leukotoxins has expanded to include more therapeutic drugs,
      drugs of abuse, and environmental insults. While the understanding of
      pathophysiology remains incomplete, TL is increasingly common in clinical
      practice, and the potential long-term cognitive sequelae of toxic white matter
      injury merit attention.

PMID- 28506193
TI  - Experiences of partners of prostate cancer survivors: A qualitative study.
AB  - Prostate cancer, Australia's leading cancer, has treatment side effects that
      reduce the quality of life for both survivors and partners. Limited partner
      research exists. This study aimed to address this gap in the literature by
      gathering data directly from partners to obtain a deeper understanding of their
      experiences of prostate cancer survivorship that helps inform healthcare service
      providers. A qualitative approach was taken to explore participant views (N = 16)
      through three focus groups and two in-depth interviews. Five themes emerged
      relating to caregiver burden, knowledge deficit, isolation, changes of sexual
      relations, and unmet needs. Possible implications for practice may include the
      need for specific partner-related information and interventions to assist couples
      to cope with the emotional distress caused by treatment side effects.

PMID- 28506194
TI  - The use of systemic therapies to prevent progression of inflammatory breast
      cancer: which targeted therapies to add on cytotoxic combinations?
AB  - INTRODUCTION: Inflammatory breast cancer is a rare but frequently fatal disease,
      essentially because of its high ability to develop distant metastases. Even
      though the prognosis of IBC was significantly improved by multimodal management,
      including the systematic use of cytotoxic-based induction, the prognosis remains
      largely dismal. Areas covered: This review presents the main achievements in the
      systemic treatment of IBC during the past 30 years. It focuses more specifically
      on recent results obtained with targeted therapies, including anti-HER2 and anti
      angiogenic agents. Novel approaches under investigation are presented. Expert
      commentary: Current management of IBC is subtype-specific and the largest benefit
      has been achieved in HER2-positive disease. The identification of breakthrough
      therapeutic advances is eagerly awaited and will require the development of IBC
      specific clinical trials. Future clinical investigations should not only aim to
      increase the pathological response rate but also to eradicate distant metastases,
      which ultimately lead to patient death.

PMID- 28506196
TI  - Sir William Harvey, Congenital Heart Disease and Anesthesia.

PMID- 28506197
TI  - High-resolution mass spectrometry confirms the presence of a hydroxyproline (Hyp)
      post-translational modification in the GGGGP linker of an Fc-fusion protein.
AB  - Flexible and protease resistant (G4S)n linkers are used extensively in protein
      engineering to connect various protein domains. Recently, several groups have
      observed xylose-based O-glycosylation at linker Ser residues that yield unwanted
      heterogeneity and may affect product quality. Because of this, an engineering
      effort was implemented to explore different linker sequence constructs. Here, we
      demonstrate the presence of an unexpected hydroxylation of a prolyl residue in
      the linker, made possible through the use of high-resolution mass spectrometry
      (HR-MS) and MSn. The discovery started with the detection of a poorly resolved
      ~+17 Da mass addition at the reduced protein chain level of an Fc-fusion
      construct by liquid chromatography-MS. Upon further investigation at the peptide
      level using HR-MS, the mass increase was determined to be +15.99 Da and was
      localized to the linker peptide SLSLSPGGGGGPAR [210-223]. This peptide
      corresponds to the C-terminus of Fc [210-216], the G4P linker [217-221], and
      first 2 amino acids of a growth factor [222-223]. The linker peptide was first
      subjected to MS2 with collision-induced dissociation (CID) activation. The
      fragmentation profile localized the modification to the GGGPA [218-222] portion
      of the peptide. Accurate mass measurement indicated that the modification is an
      addition of an oxygen and cannot be CH4, thus eliminating several possibilities
      such as Pro->Leu. However, other possibilities cannot be ruled out. Higher-energy
      collision-induced dissociation (HCD)-MS2 and MS3 using CID/CID were both unable
      to differentiate between Ala222-> Ser222 or Pro221-> Hyp221. Finally, MS3 using
      high-resolution CID/HCD confirmed the mass increase to be a Pro221->Hyp221 post
      translational modification.

PMID- 28506200
TI  - Welcome note.

PMID- 28506201
TI  - Abstracts for the 22nd Meeting of the European Society of Neurosonology and
      Cerebral Hemodynamics (ESNCH), 19-21 May 2017, Berlin.

PMID- 28506198
TI  - Naturally occurring benzoic acid derivatives retard cancer cell growth by
      inhibiting histone deacetylases (HDAC).
AB  - Histone deacetylases (HDACs), which modulate the expression of genes, are
      potential therapeutic targets in several cancers. Targeted inhibition of HDAC
      prevents the expression of oncogenes thereby help in the treatment of cancers.
      Hence, several pharmaceutical companies developed inhibitors of HDAC and tested
      them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic
      acid) is one such HDAC inhibitor developed for treating breast and colorectal
      carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA
      for treating cancers was discouraged. Similarly another HDAC inhibitor
      Trichostatin-A (TSA) also showed promising results in clinical trials but
      exhibited severe adverse effects, which dampened the interest of using this
      molecule for cancer treatment. Therefore, search for developing a potent HDAC
      inhibitor with minimal side effects still continues. Hence, in this study we have
      screened benzoic acid and benzoic acid derivatives with hydroxylic (-OH) groups
      and methoxy (-OCH3) groups for their efficacy to bind to the TSA binding site of
      HDAC using molecular docking studies. Molecules that showed much stronger
      affinity (than TSA) to HDAC were tested for inhibiting HDAC expressing cultured
      cancer cells. DHBA but not Dimethoxy Benzoic Acid (DMBA) inhibited HDAC activity,
      leading to cancer cell growth inhibition through the induction of ROS and
      cellular apoptosis mediated by Caspase-3. In addition, DHBA arrested cells in
      G2/M phase of the cell cycle and elevated the levels of sub-G0-G1 cell
      population. In summary, results of this study report that DHBA could be a strong
      HDAC inhibitor and inhibit cancer cell growth more effectively.

PMID- 28506202
TI  - Subtle and Severe: Microaggressions Among Racially Diverse Sexual Minorities.
AB  - In recent years, understanding prejudice and discrimination toward minorities has
      developed to include the investigation of microaggressions. Microaggressions are
      brief and commonplace verbal, behavioral, or environmental indignities. They are
      intentional or unintentional and communicate hostile, derogatory, or negative
      slights toward racial and sexual minorities. The purpose of this phenomenological
      study is to chronicle the prevalence and type of microaggressions experienced
      among a sample of 18 highly educated and racially diverse sexual minorities, 24
      65 years of age. The impact of microaggressions on physical and psychological
      health is central to our investigation. Thematic data analysis was used to
      analyze 14 interviews and one focus group, which resulted in the following themes
      of microaggressions: (a) discomfort/disapproval with LGBT experience, (b)
      assumption of universal experience, (c) traditional gender role stereotyping, (d)
      denial of personal privacy, (e) exoticization, (f) ascription of intelligence,
      (g) policing bodies, and (h) assumption of criminality. Research findings may
      have implications for the development of interventions that can serve clinicians
      in their therapeutic work with microaggressed sexual minorities across racial
      diversity.

PMID- 28506203
TI  - Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.
AB  - BACKGROUND: Triamcinolone is a long acting corticosteroid used in the treatment
      of arthritis, eczema, psoriasis and similar conditions which cause inflammation.
      Triamcinolone has half-life of 88min. Prolonged oral use is associated with
      gastrointestinal adverse effects as peptic ulcer, abdominal distention and
      ulcerative esophagitis as described in various patents. Microemulgel offers
      advantage of better stability, better loading capacity and controlled release
      especially for drug with short half life. OBJECTIVE: Objective of the present
      study was to optimize microemulgel based transdermal delivery of triamcinolone.
      METHOD: Saturated solubility of triamcinolone in various oils, surfactants and co
      surfactants is estimated. Pseudo-ternary phase diagrams were constructed to
      determine the region of transparent microemulsion. Microemulsion was evaluated
      for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity,
      conductivity etc. Design of experiment was used to optimize microemulsion based
      gel. Carbopol 971P and HPMC K100M were used as independent variables.
      Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters.
      RESULTS: Microemulsion was formulated with oleic acid, lauroglycol FCC and
      propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32
      factorial design gave batch F8 as optimized. Design expert suggested drug
      release; gel viscosity and bio-adhesive strength were three significant dependant
      factors affecting the transdermal delivery. F8 showed drug release 92.62.16+/
      1.22% through egg membrane, 95.23+/-1.44% through goat skin after 8hr and
      Korsmeyer-Peppas release model was followed. CONCLUSION: It can be concluded that
      a stable, effective controlled release transdermal microemulgel was optimised for
      triamcinolone. This would be a promising tool to deliver triamcinolone with
      enhanced bioavailability and reduced dosing frequency.

PMID- 28506204
TI  - Antibiotic Effects of Loperamide: Homology of Human Targets of Loperamide with
      Targets in Acanthamoeba spp.
AB  - BACKGROUND: Loperamide is an anti-diarrheal drug prescribed for non-infectious
      diarrhea. The drug is an opioid receptor agonist, blocker of voltage-dependent
      calcium channel (Cav) and calmodulin (CaM) inhibitor on human cells. Loperamide
      has been reported to exert anti-amoebic effects against pathogenic strains of
      Acanthamoeba castellanii. OBJECTIVES: The precise mode of antibiotic action,
      cellular target homology with human counterparts and the pattern of cell death
      induced by loperamide in Acanthamoeba castellanii remain to be established.
      Additionally, we attempt to establish the presence a primitive Cav in
      Acanthamoeba castellanii. METHODS: Bioinformatics, 3D structural modelling,
      ligand binding predictions and apoptotic/ amoebicidal assays were used in this
      study to answer the above queries. Amino acid sequences and structural models
      were compared between human and A. castellanii proteins that are involved in the
      regulation of calcium (Ca+2) homeostasis. RESULTS: Our results show that A.
      castellanii expresses similar, to near identical types of primitive calcium
      channels Cav Ac and CaM that are well known targets of loperamide in humans. The
      growth assays showed anti-amoebic effects of loperamide at different doses, both
      alone and in combinations with other Ca+2- CaM inhibitors. The synergistic
      actions of loperamide with haloperidol showed to be more amoebicidal than when
      either of them used alone. Imaging with Annexin V, Acridine orange and Propidium
      iodide showed apoptosis in A. castellanii at a dose of 100 ug/ml and necrosis at
      higher doses of 250 ug/ml. CONCLUSION: Though, Acanthamoeba does not express a
      homolog of the human mu-opioid receptor, but does shows evidence of the homologs
      for other known human targets of loperamide that are involved in Ca+2 uptake and
      Ca+2 signal transduction pathways. This suggests optimization of similar drug
      interactions with these targets may be useful in developing new approaches to
      control the growth of this parasite and possibly the diseases caused by it.

PMID- 28506205
TI  - In silico pathway analysis and tissue specific cis-eQTL for colorectal cancer
      GWAS risk variants.
AB  - BACKGROUND: Genome-wide association studies have identified 55 genetic variants
      associated with colorectal cancer risk to date. However, potential causal genes
      and pathways regulated by these risk variants remain to be characterized.
      Therefore, we performed gene ontology enrichment and pathway analyses to
      determine if there was an enrichment of genes in proximity to the colorectal
      cancer risk variants that could further elucidate the probable causal genes and
      pathways involved in colorectal cancer biology. RESULTS: For the 65 unique genes
      that either contained, or were immediately neighboring up- and downstream, of
      these variants there was a significant enrichment for the KEGG pathway, Pathways
      in Cancer (p-value = 2.67 * 10-5) and an enrichment for multiple biological
      processes (FDR < 0.05), such as cell junction organization, tissue morphogenesis,
      regulation of SMAD protein phosphorylation, and odontogenesis identified through
      Gene Ontology analysis. To identify potential causal genes, we conducted a cis
      expression quantitative trait loci (cis-eQTL) analysis using gene expression and
      genotype data from the Genotype-Tissue Expression (GTEx) Project portal in normal
      sigmoid (n = 124) and transverse (n = 169) colon tissue. In addition, we also did
      a cis-eQTL analysis on colorectal tumor tissue (n = 147) from The Cancer Genome
      Atlas (TCGA). We identified two risk alleles that were significant cis-eQTLs for
      FADS2 (rs1535) and COLCA1 and 2 (rs3802842) genes in the normal transverse colon
      tissue and two risk alleles that were significant cis-eQTLs for the CABLES2
      (rs2427308) and LIPG (rs7229639) genes in the normal sigmoid colon tissue, but
      not tumor tissue. CONCLUSIONS: Our data reaffirm the potential to identify an
      enrichment for biological processes and candidate causal genes based on
      expression profiles correlated with genetic risk alleles of colorectal cancer,
      however, the identification of these significant cis-eQTLs is context and tissue
      specific.

PMID- 28506206
TI  - Females of a gift-giving spider do not trade sex for food gifts: a consequence of
      male deception?
AB  - BACKGROUND: Polyandry is commonly maintained by direct benefits in gift-giving
      species, so females may remate as an adaptive foraging strategy. However, the
      assumption of a direct benefit fades in mating systems where male gift-giving
      behaviour has evolved from offering nutritive to worthless (non-nutritive) items.
      In the spider Paratrechalea ornata, 70% of gifts in nature are worthless. We
      therefore predicted female receptivity to be independent of hunger in this
      species. We exposed poorly-fed and well-fed females to multiple males offering
      nutritive gifts and well-fed females to males offering worthless gifts. RESULTS:
      Though the treatments strongly affected fecundity, females of all groups had
      similar number of matings. This confirms that female receptivity is independent
      of their nutritional state, i.e. polyandry does not prevail as a foraging
      strategy. CONCLUSIONS: In the spider Pisaura mirabilis, in which the majority
      (62%) of gifts in nature are nutritive, female receptivity depends on hunger. We
      therefore propose that the dependence of female receptivity on hunger state may
      have evolved in species with predominantly nutritive gifts but is absent in
      species with predominantly worthless gifts.

PMID- 28506207
TI  - The midgut transcriptome of Aedes aegypti fed with saline or protein meals
      containing chikungunya virus reveals genes potentially involved in viral midgut
      escape.
AB  - BACKGROUND: The mosquito Aedes aegypti is the primary vector for medically
      important arthropod-borne viruses, including chikungunya virus (CHIKV). Following
      oral acquisition, an arbovirus has to persistently infect several organs in the
      mosquito before becoming transmissible to another vertebrate host. A major
      obstacle an arbovirus has to overcome during its infection cycle inside the
      mosquito is the midgut escape barrier, representing the exit mechanism
      arboviruses utilize when disseminating from the midgut. To understand the
      transcriptomic basis of midgut escape and to reveal genes involved in the
      process, we conducted a comparative transcriptomic analysis of midgut samples
      from mosquitoes which had received a saline meal (SM) or a protein meal (PM)
      (not) containing CHIKV. RESULTS: CHIKV which was orally acquired by a mosquito
      along with a SM or PM productively infected the midgut epithelium and
      disseminated to secondary tissues. A total of 27 RNA-Seq libraries from midguts
      of mosquitoes that had received PM or SM (not) containing CHIKV at 1 and 2 days
      post-feeding were generated and sequenced. Fewer than 80 genes responded
      differentially to the presence of CHIKV in midguts of mosquitoes that had
      acquired the virus along with SM or PM. SM feeding induced differential
      expression (DE) of 479 genes at day 1 and 314 genes at day 2 when compared to
      midguts of sugarfed mosquitoes. By comparison, PM feeding induced 6029 DE genes
      at day 1 and 7368 genes at day 2. Twenty-three DE genes encoding trypsins,
      metalloproteinases, and serine-type endopeptidases were significantly upregulated
      in midguts of mosquitoes at day 1 following SM or PM ingestion. Two of these
      genes were Ae. aegypti late trypsin (AeLT) and serine collagenase 1 precursor
      (AeSP1). In vitro, recombinant AeLT showed strong matrix metalloproteinase
      activity whereas recombinant AeSP1 did not. CONCLUSIONS: By substituting a
      bloodmeal for SM, we identified midgut-expressed genes not involved in blood or
      protein digestion. These included genes coding for trypsins, metalloproteinases,
      and serine-type endopeptidases, which could be involved in facilitating midgut
      escape for arboviruses in Ae. aegypti. The presence of CHIKV in any of the
      ingested meals had relatively minor effects on the overall gene expression
      profiles in midguts.

PMID- 28506208
TI  - A strategy to apply quantitative epistasis analysis on developmental traits.
AB  - BACKGROUND: Genetic interactions are keys to understand complex traits and
      evolution. Epistasis analysis is an effective method to map genetic interactions.
      Large-scale quantitative epistasis analysis has been well established for single
      cells. However, there is a substantial lack of such studies in multicellular
      organisms and their complex phenotypes such as development. Here we present a
      method to extend quantitative epistasis analysis to developmental traits.
      METHODS: In the nematode Caenorhabditis elegans, we applied RNA interference on
      mutants to inactivate two genes, used an imaging system to quantitatively measure
      phenotypes, and developed a set of statistical methods to extract genetic
      interactions from phenotypic measurement. RESULTS: Using two different C. elegans
      developmental phenotypes, body length and sex ratio, as examples, we showed that
      this method could accommodate various metazoan phenotypes with performances
      comparable to those methods in single cell growth studies. Comparing with
      qualitative observations, this method of quantitative epistasis enabled detection
      of new interactions involving subtle phenotypes. For example, several sex-ratio
      genes were found to interact with brc-1 and brd-1, the orthologs of the human
      breast cancer genes BRCA1 and BARD1, respectively. We confirmed the brc-1
      interactions with the following genes in DNA damage response: C34F6.1, him-3
      (ortholog of HORMAD1, HORMAD2), sdc-1, and set-2 (ortholog of SETD1A, SETD1B,
      KMT2C, KMT2D), validating the effectiveness of our method in detecting genetic
      interactions. CONCLUSIONS: We developed a reliable, high-throughput method for
      quantitative epistasis analysis of developmental phenotypes.

PMID- 28506209
TI  - Peptides mimicking viral proteins of porcine circovirus type 2 were profiled by
      the spectrum of mouse anti-PCV2 antibodies.
AB  - BACKGROUND: Porcine circovirus 2 (PCV2) is a small, non-enveloped DNA virus
      causing swine lymphocyte depletion and severe impact on the swine industry. The
      aim of this study was to evaluate the antigenicity and immunogenicity of specific
      peptides, and seeking the potential candidate of PCV2 peptide-based vaccine. It's
      initiating from peptides reacting with PCV2-infected pig sera and peptide
      immunized mouse sera. RESULTS: The data showed that the sera from PCV2-infected
      pigs could react with the N-terminal (C1), middle region (C2), and C-terminal
      peptide (C3) of PCV2 capsid protein (CP), ORF3 protein (N1), ORF6 protein (N2)
      and ORF9 protein (N3). This study demonstrated that anti-PCV2 mouse antisera
      could be generated by specific synthetic peptides (C3 and N2) and recognized PCV2
      viral protein. We found that the tertiary or linear form C-terminal sequence (C3)
      of PCV2 capsid peptide only appeared a local distribution in the nucleus of PCV2
      infected PK cells, virus-like particles of PCV2 major appeared a local
      distribution in the cytoplasm, and ORF 6 protein of PCV2 were shown unusually in
      cytoplasm. Furthermore, most residues of the C1 and the C3 were presented on the
      surface of PCV2 CP, in the view of 3-D structure of the CP. Our data demonstrated
      that PCV2-infected pigs had higher OD405 value of anti-C3 IgG on Day 1, Month 3
      and Month 6 than in Month 1. These pigs had higher anti-C3 IgM level in Month 3
      and Month 6 than on Day 1 (P < 0.01). CONCLUSIONS: We demonstrated that the key
      peptide (C3) mimic the C-terminal of PCV2 capsid protein which were capable of
      inducing antibodies. The specific antibody against the C3 were confirmed as the
      serological marker in PCV2-infected pigs.

PMID- 28506210
TI  - Sucrose non-ferment 1 related protein kinase 2 (SnRK2) genes could mediate the
      stress responses in potato (Solanum tuberosum L.).
AB  - BACKGROUND: The SnRKs (sucrose non-fermenting 1 related protein kinase) are a
      gene family coding for Ser/Thr protein kinases and play important roles in
      linking the tolerance and metabolic responses of plants to abiotic stresses. To
      date, no genome-wide characterization of the sucrose non-ferment 1 related
      protein kinase 2 (SnRK2) subfamily has been conducted in potato (Solanum
      tuberosum L.). RESULTS: In this study, eight StSnRK2 genes (StSnRK2.1- StSnRK2.8)
      were identified in the genome of the potato (Solanum tuberosum L.) cultivar
      'Longshu 3', with similar characteristics to SnRK2 from other plant species in
      gene structure, motif distribution and secondary structures. The C-terminal
      regions were highly divergent among StSnRK2s, while they all carried the similar
      Ser/Thr protein kinase domain. The fluorescence of GFP fused with StSnRK2.1,
      StSnRK2.2, StSnRK2.6, StSnRK2.7 and StSnRK2.8 was detected in the nucleus and
      cytoplasm of onion epidermal cells with StSnRK2.3 and StSnRK2.4 mainly associated
      to the nucleus while StSnRK2.5 to subcellular organelles. Expression level
      analysis by qRT-PCR showed that StSnRK2.1, 2.2, 2.5 and 2.6 were more than 1 fold
      higher in the root than in the leaf, tuber and stem tissues. The expressions of
      StSnRK2.3, 2.7, and 2.8 were at least 1.5 folds higher in the leaf and stem than
      in the root, but lower in the tuber. The expression of StSnRK2.4 was also
      significantly (P < 0.05) higher in leaf, stem, and tuber than in the root. From
      the perspective of the relative expressions of StSnRK2 genes in potato, ABA
      treatment had a different effect from NaCl and PEG treatments. CONCLUSION: In the
      present study, we identified and characterized eight SnRK2s in the potato genome.
      The eight StSnRK2s exhibit similar gene structure and secondary structures in
      potato to the SnRK2s found in other plant species. The relative expression of
      eight genes varied among various tissues (roots, leaves, tubers, and stems) and
      abiotic stresses (ABA, NaCl and PEG-6000) with the prolongation of treatments.
      This study provides valuable information for the future functional dissection of
      potato SnRK2 genes in stress signal transduction, plant growth and development.

PMID- 28506211
TI  - Interstitial pneumonia pattern on day 7 chest radiograph predicts
      bronchopulmonary dysplasia in preterm infants.
AB  - BACKGROUND: Early identification of infants at higher risk of developing
      bronchopulmonary dysplasia (BPD) may enable a targeted approach to reduce BPD. We
      aimed to evaluate the hypothesis that the interstitial pneumonia pattern on the
      day 7 chest radiograph predicts BPD or death before 36 weeks postmenstrual age
      (PMA). METHODS: A retrospective cohort study was performed on 336 preterm infants
      (birth weight < 1500 g and gestational age < 32 postmenstrual weeks) who were
      admitted to a single tertiary academic center between January 2008 and December
      2014. Day 7 chest radiographs were independently reviewed by two pediatric
      radiologists who were unaware of the clinical information regarding each
      individual infant. RESULTS: Data from 304 infants who survived more than 7 days
      after birth were collected. The interstitial pneumonia pattern on the day 7 chest
      radiograph was independently associated with BPD or death before 36 weeks PMA
      (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.1-14.4). The interstitial
      pneumonia pattern on the day 7 chest radiograph predicted BPD or death with a
      specificity of 98%. Histologic chorioamnionitis was a preceding factor that was
      independently associated with the interstitial pneumonia pattern on the day 7
      chest radiograph (OR 3.7, 95% CI 1.3-10.3). CONCLUSIONS: The interstitial
      pneumonia pattern on the day 7 chest radiograph has a high specificity for
      predicting BPD or death and can be utilized to select high-risk preterm infants
      who will benefit from potentially preventive interventions against BPD.

PMID- 28506212
TI  - GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas
      nucleases.
AB  - BACKGROUND: Genome editing technologies developed around the CRISPR-Cas9 nuclease
      system have facilitated the investigation of a broad range of biological
      questions. These nucleases also hold tremendous promise for treating a variety of
      genetic disorders. In the context of their therapeutic application, it is
      important to identify the spectrum of genomic sequences that are cleaved by a
      candidate nuclease when programmed with a particular guide RNA, as well as the
      cleavage efficiency of these sites. Powerful new experimental approaches, such as
      GUIDE-seq, facilitate the sensitive, unbiased genome-wide detection of nuclease
      cleavage sites within the genome. Flexible bioinformatics analysis tools for
      processing GUIDE-seq data are needed. RESULTS: Here, we describe an open source,
      open development software suite, GUIDEseq, for GUIDE-seq data analysis and
      annotation as a Bioconductor package in R. The GUIDEseq package provides a
      flexible platform with more than 60 adjustable parameters for the analysis of
      datasets associated with custom nuclease applications. These parameters allow
      data analysis to be tailored to different nuclease platforms with different
      length and complexity in their guide and PAM recognition sequences or their DNA
      cleavage position. They also enable users to customize sequence aggregation
      criteria, and vary peak calling thresholds that can influence the number of
      potential off-target sites recovered. GUIDEseq also annotates potential off
      target sites that overlap with genes based on genome annotation information, as
      these may be the most important off-target sites for further characterization. In
      addition, GUIDEseq enables the comparison and visualization of off-target site
      overlap between different datasets for a rapid comparison of different nuclease
      configurations or experimental conditions. For each identified off-target, the
      GUIDEseq package outputs mapped GUIDE-Seq read count as well as cleavage score
      from a user specified off-target cleavage score prediction algorithm permitting
      the identification of genomic sequences with unexpected cleavage activity.
      CONCLUSION: The GUIDEseq package enables analysis of GUIDE-data from various
      nuclease platforms for any species with a defined genomic sequence. This software
      package has been used successfully to analyze several GUIDE-seq datasets. The
      software, source code and documentation are freely available at
      http://www.bioconductor.org/packages/release/bioc/html/GUIDEseq.html .

PMID- 28506214
TI  - Origins location of the outflow tract ventricular arrhythmias exhibiting qrS
      pattern or QS pattern with a notch on the descending limb in lead V1.
AB  - BACKGROUND: Ventricular outflow tract(VOT) ventricular arrhythmias(VAs)
      presenting qrS pattern or QS pattern with a notch on the descending limb in lead
      V1 were consistently thought of arising from the commissure between left and
      right coronary cusp (L-RCC) by previous studies. However, we found they could
      originate from other anatomic structures in VOT. This study aimed to investigate
      the exact origin of this kind VAs. METHODS: Forty-nine patients of VOT premature
      ventricular contrations/ventricular tachycardia(PVCs/VT) with lead V1 presenting
      qrS pattern or QS pattern with a notch on the descending limb undergoing
      successful radiofrequency catheter ablation(RFCA) in our center were analyzed.
      RESULTS: 12-lead electrocardiogram(ECG) of these PVCs/VT were summarized. Among
      these PVCs/VT, 37 cases exhibited qrS morphology in lead V1, 12 cases presented
      QS pattern with a notch on the descending limb in the same lead. Based on the
      successful ablation sites, these PVCs/VT were divided into 2 groups: (1)Right
      ventricular outflow tract(RVOT) group (26 cases), and (2) Left ventricular
      outflow tract (LVOT) group(23 cases, 4 cases originating from the left coronary
      cusp(LCC), 2 from the right coronary cusp(RCC), 16 from the L-RCC, 1 from the
      area inferior to LCC(ILCC)). The ECG characteristics of each PVCs/VT were
      analyzed. Among these PVCs/VT, applying the precordial transitional zone index(TZ
      index) < 0 to predict LVOT origin was demonstrated with sensitivity of 95.65%,
      specificity of 96.15%, positive predicting value(PPV) of 95.65% and negative
      predicting value(NPV) of 96.15%. In LVOT group, further applying the r, R, m,or
      Rs morphology in lead I to predict L-RCC and RCC origin was demonstrated with
      sensitivity of 94.44%, specificity of 60.00%, PPV of 89.47% and NPV of 75.00%.
      CONCLUSIONS: Ventricular outflow tract PVCs/VT with lead V1 presenting qrS
      pattern or QS pattern with a notch on descending limb not only arising from L
      RCC, but also RVOT, LCC, RCC and ILCC. Combining TZ index and QRS morphology in
      lead I to predict origin site of these kind VAs is a convenient, simple and
      reliable method and facilitates the RFCA procedure.

PMID- 28506213
TI  - Voxel-wise correlations between cognition and cerebral blood flow using arterial
      spin-labeled perfusion MRI in patients with Alzheimer's disease: a cross
      sectional study.
AB  - BACKGROUND: To analyze voxel-wise correlation between cerebral blood flow (CBF)
      measured using ASL-MRI and cognition in patients with Alzheimer's disease (AD).
      METHODS: Forty-one patients diagnosed with AD or mild cognitive impairment due to
      AD were recruited for this study. CBF images were obtained using ASL-MRI (n = 41)
      with a post-labeling delay (PLD) of 1.5 and 2.5 s (PLD1.5 and PLD2.5,
      respectively) using a 3 T scanner, in addition to brain perfusion SPECT with N
      isopropyl-4-[I-123]iodoamphetamine (n = 28). Voxel-based analyses were performed
      for ASL-MRI and SPECT using Mini-Mental State Examination (MMSE) scores as
      covariates. Differences in CBF between PLD1.5 and PLD2.5 were assessed using a
      paired t-test with SPM12. RESULTS: Significant positive correlations were
      observed between MMSE scores and CBF at PLD1.5 in the right posterior cingulate
      cortex (PCC), and both temporo-parietal association cortexes. At PLD2.5,
      significant positive correlations were determined for MMSE scores and CBF in the
      superior parietal lobule and the right temporo-parietal association cortex. SPECT
      showed significant positive correlations in the PCC and both temporo-parietal
      association cortexes (right-side dominant). PLD1.5 showed significantly higher
      CBF than PLD2.5 in the proximal areas of vascular territories of the anterior,
      middle, and posterior cerebral arteries. CONCLUSIONS: Significant positive
      correlations in CBF, measured with both ASL-MRI and SPECT, with cognition were
      found in the PCC and temporo-parietal association cortexes. PLD1.5 and PLD2.5
      showed similar correlations with cognition, although the CBF images had
      significant differences.

PMID- 28506215
TI  - Comparison of antibody responses against Mycobacterium tuberculosis antigen
      Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the
      Beijing genotype: a case control study.
AB  - BACKGROUND: Strains of the Beijing genotype of Mycobacterium tuberculosis (MTB)
      are reportedly associated with the virulence of tuberculosis (TB) infection,
      unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a
      hypothetical membrane protein related to host cell invasion, has a Beijing
      genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences
      between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously
      observed in mice antigen-antibody responses. However, the immune response to
      Rv0679c in humans remains unknown. Therefore, we aimed to investigate the anti
      Rv0679c immune response in TB patients from the endemic and non-endemic regions
      of the Beijing MTB genotype. METHODS: We analyzed the Rv0679c-specific antibody
      responses in 84 subjects from the endemic region of the Beijing genotype MTB in
      China, including 45 pulmonary TB patients (C-PTB) and 39 healthy controls (C-HC),
      and 81 subjects from the Philippines (the endemic region of the non-Beijing
      genotype), including 51 pulmonary TB patients (P-PTB) and 30 healthy controls (P
      HC). Anti-tuberculous-glycolipid (TBGL) antigen was used as the control antibody.
      RESULTS: TBGL IgG titers were higher in both C-PTB and P-PTB than those in their
      corresponding HC (C-PTB median 4.2, P-PTB median 11.2; C-PTB vs. P-PTB, p >
      0.05), suggesting immune response comparability in PTB from two different
      countries. C-PTB showed a higher response compared to C-HC for anti-K-type IgG
      (53.3%) than anti-N-type IgG (6.67%); this response was not observed in P-PTB
      (both N-type and K-type 9.80%). CONCLUSION: Dimorphic antigen Rv0679c was found
      to be associated with distinct immune response patterns, indicating the role of
      Beijing/non-Beijing genotype of MTB in stimulating specific responses in TB
      patients from the endemic region of Beijing MTB. Meanwhile, reactions to Rv0679c
      in patients and HC from non-endemic regions of the Beijing MTB may be caused by
      the response to the common epitope of Rv0679c N/K-type.

PMID- 28506216
TI  - Nutritional determinants of frailty in older adults: A systematic review.
AB  - BACKGROUND: Frailty is a geriatric syndrome that affects multiple domains of
      human functioning. A variety of problems contributes to the development of this
      syndrome; poor nutritional status is an important determinant of this condition.
      The purpose of this systematic review was to examine recent evidence regarding
      the association between nutritional status and frailty syndrome in older adults.
      METHODS: PubMed, Web of Science, and Scopus electronic databases were searched
      using specific key words, for observational papers that were published during the
      period from 2005 to February 2017 and that studied the association or
      relationship between nutritional status and frailty in older adults. The
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      Statement was followed to assess the quality of the included articles. RESULTS:
      Of the 2042 studies found, nineteen met the inclusion criteria. Of these studies,
      five provided data on micronutrients and frailty, and reported that frailty
      syndrome is associated with low intakes of specific micronutrients. Five studies
      provided data on macronutrients and frailty, and among those studies, four
      revealed that a higher protein intake was associated with a lower risk of
      frailty. Three studies examined the relationship between diet quality and
      frailty, and showed that the quality of the diet is inversely associated with the
      risk of being frail. Two studies provided data on the antioxidant capacity of the
      diet and frailty, and reported that a high dietary antioxidant capacity is
      associated with a lower risk of developing frailty. Finally, seven studies
      evaluated the relationship between scores on both the Mini Nutritional Assessment
      (MNA) and the MNA-SF (Short Form) and frailty, and revealed an association
      between malnutrition and/or the risk of malnutrition and frailty. CONCLUSIONS:
      This systematic review confirms the importance of both quantitative (energy
      intake) and qualitative (nutrient quality) factors of nutrition in the
      development of frailty syndrome in older adults. However, more longitudinal
      studies on this topic are required to further understand the potential role of
      nutrition in the prevention, postponement, or even reversion of frailty syndrome.

PMID- 28506217
TI  - Association between maternal social deprivation and prenatal care utilization:
      the PreCARE cohort study.
AB  - BACKGROUND: Maternal social deprivation is associated with an increased risk of
      adverse maternal and perinatal outcomes. Inadequate prenatal care utilization
      (PCU) is likely to be an important intermediate factor. The health care system in
      France provides essential health services to all pregnant women irrespective of
      their socioeconomic status. Our aim was to assess the association between
      maternal social deprivation and PCU. METHODS: The analysis was performed in the
      database of the multicenter prospective PreCARE cohort study. The population
      source consisted in all parturient women registered for delivery in 4 university
      hospital maternity units, Paris, France, from October 2010 to November 2011 (N =
      10,419). This analysis selected women with singleton pregnancies that ended after
      22 weeks of gestation (N = 9770). The associations between maternal deprivation
      (four variables first considered separately and then combined as a social
      deprivation index: social isolation, poor or insecure housing conditions, no work
      related household income, and absence of standard health insurance) and
      inadequate PCU were tested through multivariate logistic regressions also
      adjusted for immigration characteristics and education level. RESULTS: Attendance
      at prenatal care was poor for 23.3% of the study population. Crude relative risks
      and confidence intervals for inadequate PCU were 1.6 [1.5-1.8], 2.3 [2.1-2.6],
      and 3.1 [2.8-3.4], for women with a deprivation index of 1, 2, and 3,
      respectively, compared to women with deprivation index of 0. Each of the four
      deprivation variables was significantly associated with an increased risk of
      inadequate PCU. Because of the interaction observed between inadequate PCU and
      mother's country of birth, we stratified for the latter before the multivariate
      analysis. After adjustment for the potential confounders, this social gradient
      remained for women born in France and North Africa. The prevalence of inadequate
      PCU among women born in sub-Saharan Africa was 34.7%; the social gradient in this
      group was attenuated and no longer significant. Other factors independently
      associated with inadequate PCU were maternal age, recent immigration, and
      unplanned or unwanted pregnancy. CONCLUSION: Social deprivation is independently
      associated with an increased risk of inadequate PCU. Recognition of risk factors
      is an important step in identifying barriers to PCU and developing measures to
      overcome them.

PMID- 28506218
TI  - Investigation of the pathophysiology of cardiopulmonary bypass using rodent
      extracorporeal life support model.
AB  - BACKGROUND: Extracorporeal life support (ECLS) systems are life-saving devices
      used for treating patients with severe cardiopulmonary failure. In this study, we
      implemented a rat model of ECLS without the administration of inotropes or
      vasopressors. METHODS: The rats underwent 5 min of untreated asphyxial cardiac
      arrest and were resuscitated by ECLS for 30 min. The right external jugular vein
      and right femoral artery were separately cannulated to the ECLS outflow and
      inflow, respectively. Thereafter, ECLS was terminated, wounds were closed, and
      mechanical ventilation was provided for another 90 min. Subsequently, blood gas
      and hemodynamic analyses were performed. The plasma levels of C-reactive protein
      (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-alpha)
      were measured 120 min after reperfusion. RESULTS: The metabolic rate of lactate
      in the group of asphyxial cardiac arrest rescued by ECLS was slow; therefore, the
      pH at 120 min after reperfusion was significantly lower in this group than that
      in the group of normal rats treated with ECLS. The hemodynamic data showed no
      between-group differences. The plasma levels of CRP, IL-6, IL-10, and TNF-alpha
      increased after ECLS treatment. CONCLUSIONS: We successfully established a rodent
      ECLS model, which might be a useful approach for studying the pathophysiology
      induced by ECLS under clinical conditions.

PMID- 28506219
TI  - Sexual orientation differences in treatment expectation, alliance, and outcome
      among patients at risk for suicide in a public psychiatric hospital.
AB  - BACKGROUND: Sexual minority (SM) individuals (gay, lesbian, bisexual, or
      otherwise nonheterosexual) are at increased risk for mental disorders and suicide
      and adequate mental healthcare may be life-saving. However, SM patients
      experience barriers in mental healthcare that have been attributed to the lack of
      SM-specific competencies and heterosexist attitudes and behaviors on the part of
      mental health professionals. Such barriers could have a negative impact on common
      treatment factors such as treatment expectancy or therapeutic alliance,
      culminating in poorer treatment outcomes for SM versus heterosexual patients.
      Actual empirical data from general psychiatric settings is lacking, however.
      Thus, comparing the treatment outcome of heterosexual and SM patients at risk for
      suicide was the primary aim of this study. The secondary aim was to compare
      treatment expectation and working alliance as two common factors. METHODS: We
      report on 633 patients from a suicide prevention inpatient department within a
      public psychiatric hospital. Most patients were at risk for suicide due to a
      recent suicide attempt or warning signs for suicide, usually in the context of a
      severe psychiatric disorder. At least one indicator of SM status was reported by
      21% of patients. We assessed the treatment outcome by calculating the
      quantitative change in suicide ideation, hopelessness, and depression. We also
      ran related treatment responder analyses. Treatment expectation and working
      alliance were the assessed common factors. RESULTS: Contrary to the primary
      hypothesis, SM and heterosexual patients were comparable in their improvement in
      suicide ideation, hopelessness, or depression, both quantitatively and in
      treatment responder analysis. Contrary to the secondary hypothesis, there were no
      significant sexual orientation differences in treatment expectation and working
      alliance. When adjusting for sociodemographics, diagnosis, and length of stay,
      some sexual orientation differences became significant, indicating that SM
      patients have better outcomes. CONCLUSIONS: These unexpected but positive
      findings may be due to common factors of therapy compensating for SM-specific
      competencies. It may also be due to actual presence of SM competencies - though
      unmeasured - in the department. Replication in other treatment settings and
      assessment of SM-specific competencies are needed, especially in the field of
      suicide prevention, before these findings can be generalized.

PMID- 28506221
TI  - The association between urbanization and reduced renal function: findings from
      the China Health and Nutrition Survey.
AB  - BACKGROUND: While chronic kidney disease (CKD) is a growing public health concern
      in low- and middle-income countries, such as China, few studies have investigated
      the association between urbanization and the occurrence of CKD in those
      countries. METHODS: We investigated the association between urbanization and
      estimated glomerular filtration rate (eGFR), an important CKD risk marker. Data
      came from the China Health and Nutrition Survey wave 2009, in which we collected
      fasting serum, individual and household data along with community level
      urbanization data, which was used to derive a study-specific urbanization
      measure, in 218 communities across nine provinces. A total of 3644 men and 4154
      women participants aged 18 years or older were included in the analysis. Reduced
      renal function was defined as eGFR of less than 60 mL/min/1.73 m2 measured using
      serum creatinine concentration (mg/dL). RESULTS: After adjusting for socio
      demographic (e.g., age, education and household income), a sex-stratified
      multilevel logistic model revealed that living in a more urbanized community was
      associated with higher odds of reduced eGFR (odds ratio [OR] = 1.38 per one
      standard deviation [SD] increase in the CHNS specific urbanization index, 95%
      confidence interval [CI] = 1.11-1.73 for men; OR = 1.35, 95% CI = 1.11-1.62 for
      women). After adjusting for behavioral variables (i.e., alcohol consumption,
      smoking, physical activity and diet), as well as obesity and cardiometabolic risk
      factors, the association was attenuated in men (OR = 1.25, 95% CI = 0.98-1.59),
      but remained statistically significant in women (OR = 1.24, 95% CI = 1.01-1.52).
      CONCLUSION: Our findings suggest that living in an urban environment is linked
      with higher odds of reduced renal function independently of behavioral and
      cardiometabolic risk factors, which have been shown to increase along with
      urbanization.

PMID- 28506220
TI  - Does the number of previous mood episodes moderate the relationship between
      alcohol use, smoking and mood in bipolar outpatients?
AB  - BACKGROUND: Evidence suggests that alcohol use and smoking are negatively
      associated with mood in bipolar disorders (BD). It is unknown if this
      relationship is moderated by the number of previous mood episodes. Therefore,
      this paper aims to examine whether the number of previous mood episodes moderates
      the relationship between alcohol use and smoking, and mood. METHOD: This study
      assessed the outcomes of 108 outpatients with BD I and II in a prospective
      observational cohort study. For 1 year, subjects daily registered mood symptoms
      and substance use with the prospective Life Chart Method. The relationship
      between the average daily consumption of alcohol and tobacco units in the whole
      year and mood were examined by multiple linear regression analyses. Number of
      previous mood episodes, grouped into its quartiles, was added as effect
      moderator. Outcome was the number of depressive, hypomanic and manic days in that
      year. RESULTS: The number of depressive days in a year increased by 4% (adjusted
      beta per unit tobacco = 1.040; 95% CI 1.003-1.079; p = 0.033) per unit increase
      in average daily tobacco consumption in that same year. Interaction analyses
      showed that in those subjects with less than 7 previous mood episodes, the number
      of manic and hypomanic days increased by 100.3% per unit increase in alcohol
      consumption (adjusted beta per unit alcohol = 2.003; 95% CI 1.225-3.274; p =
      0.006). In those with 7 to 13 previous mood episodes, the number of manic and
      hypomanic days decreased by 28.7% per unit increase in alcohol consumption
      (adjusted beta per unit alcohol = 0.713; 95% CI 0.539-0.944; p = 0.019); and in
      subjects with 14 to 44 previous mood episodes, the number of manic and hypomanic
      days decreased by 7.2% per unit increase in tobacco consumption (adjusted beta
      per unit tobacco = 0.928; 95% CI 0.871-0.989; p = 0.021). CONCLUSIONS: The number
      of previous mood episodes moderates the relationship between alcohol use and
      smoking and mood; and smoking is adversely associated with the number of
      depressive days.

PMID- 28506222
TI  - Computational fluid dynamics study of intra-arterial chemotherapy for oral
      cancer.
AB  - BACKGROUND: Intra-arterial chemotherapy (IAC) for oral cancer can deliver a
      higher concentration of anticancer agent into a tumor-feeding artery than
      intravenous systemic chemotherapy. However, distribution of anticancer agent into
      several branches of the external carotid artery (ECA) in IAC has not demonstrated
      sufficient treatment efficacy. To improve the effectiveness of IAC, the flow
      distribution of anticancer agent into the branches of the ECA in several IAC
      methods was investigated using computational fluid dynamics (CFD). METHODS:
      Patient-specific three-dimensional vessel models were created from CT images of 2
      patients with tongue cancer. Catheter models were combined with the vessel
      models. Thirty-two models were generated with varying vertical and horizontal
      positions of the catheter tip. With the use of a zero-dimensional resistance
      model of the peripheral vessel network, conventional IAC and superselective IAC
      were simulated in 30 and 2 models, respectively. The flow distribution of
      anticancer agent into the branches of the ECA was investigated in 32 models.
      Additionally, the blood streamline was traced from the inlet of the common
      carotid artery toward each outlet to examine the flow of anticancer agent in all
      models, and the wall shear stress of the vessel was calculated for some models.
      RESULTS: The CFD simulations could be conducted within a reasonable computational
      time. In several models, the anticancer agent flowed into the target artery only
      when the catheter tip was located below the bifurcation of the ECA and each
      target artery. Furthermore, the anticancer agent tended to flow into the target
      artery when the catheter tip was shifted toward the target artery. In all ECA
      branches that had flow of anticancer agent, the blood streamlines to the target
      arteries contacted the catheter tip. Anticancer agent flowed into only the target
      artery in patients' models for superselective IAC. However, high wall shear
      stress was observed at the target artery in one patient's model. CONCLUSIONS:
      This CFD study showed that location of the catheter tip was important in
      controlling the anticancer agent in conventional IAC. The distribution rate of
      anticancer agent into the tumor-feeding artery tended to increase when the
      catheter tip was placed below and toward the target artery. Although
      superselective IAC can reliably supply anticancer agent to the target artery,
      high wall shear stress at the target artery can occur, depending on vessel
      geometry of the patient, which may cause serious complications during the
      treatment.

PMID- 28506223
TI  - Case of asteroid hyalosis that developed severely reduced vision after cataract
      surgery.
AB  - BACKGROUND: To report our findings in a patient with asteroid hyalosis (AH) who
      had a severe reduction of his visual acuity following cataract surgery. The
      vision was improved by vitreous surgery. CASE PRESENTATION: The patient was an 81
      year-old man. Following cataract surgery on his left eye, his decimal best
      corrected visual acuity (BCVA) was markedly reduced from 0.2 to 0.02. A large
      number of asteroid bodies (ABs) was observed to be concentrated on the posterior
      surface of the implanted intraocular lens. Ultrasound B-mode images showed
      turbidity of the vitreous that was denser in the anterior vitreous where the ABs
      were concentrated. During vitrectomy, the ABs were observed to be concentrated in
      the anterior vitreous cavity, and a complete posterior vitreous detachment (PVD)
      was present. After vitrectomy successfully removed the ABs, the visibility of the
      fundus improved and the BCVA recovered to 1.0. CONCLUSION: We suggest that the
      visual impairment after the cataract surgery was due to the concentrated ABs in
      the anterior vitreous cavity. The clustering of the ABs in the anterior vitreous
      cavity was most likely caused by the PVD that developed during the cataract
      surgery.

PMID- 28506224
TI  - Funding and remuneration of interdisciplinary primary care teams in Canada: a
      conceptual framework and application.
AB  - BACKGROUND: Reliance on interdisciplinary teams in the delivery of primary care
      is on the rise. Funding bodies strive to design financial environments that
      support collaboration between providers. At present, the design of financial
      arrangements has been fragmented and not based on evidence. The root of the
      problem is a lack of systematic evidence demonstrating the superiority of any
      particular financial arrangement, or a solid understanding of options. In this
      study we develop a framework for the conceptualization and analysis of financial
      arrangements in interdisciplinary primary care teams. METHODS: We use qualitative
      data from three sources: (i) interviews with 19 primary care decision makers
      representing 215 clinics in three Canadian provinces, (ii) a research roundtable
      with 14 primary care decision makers and/or researchers, and (iii) policy
      documents. Transcripts from interviews and the roundtable were coded thematically
      and a framework synthesis approach was applied. RESULTS: Our conceptual framework
      differentiates between team level funding and provider level remuneration, and
      characterizes the interplay and consonance between them. Particularly the notions
      of hierarchy, segregation, and dependence of provider incomes, and the link
      between funding and team activities are introduced as new clarifying concepts,
      and their implications explored. The framework is applied to the analysis of
      collaboration incentives, which appear strongest when provider incomes are
      interdependent, funding is linked to the team as a whole, and accountability does
      not have multiple lines. Emergent implementation issues discussed by respondents
      include: (i) centrality of budget negotiations; (ii) approaches to patient
      rostering; (iii) unclear funding sources for space and equipment; and (iv)
      challenges with community engagement. The creation of patient rosters is
      perceived as a surprisingly contentious issue, and the challenges of funding for
      space and equipment remain unresolved. CONCLUSIONS: The development and
      application of a conceptual framework is an important step to the systematic
      study of the best performing financial models in the context of interdisciplinary
      primary care. The identification of optimal financial arrangements must be
      contextualized in terms of feasibility and the implementation environment. In
      general, financial hierarchy, both overt and covert, is considered a barrier to
      collaboration.

PMID- 28506225
TI  - HealthRecSys: A semantic content-based recommender system to complement health
      videos.
AB  - BACKGROUND: The Internet, and its popularity, continues to grow at an
      unprecedented pace. Watching videos online is very popular; it is estimated that
      500 h of video are uploaded onto YouTube, a video-sharing service, every minute
      and that, by 2019, video formats will comprise more than 80% of Internet traffic.
      Health-related videos are very popular on YouTube, but their quality is always a
      matter of concern. One approach to enhancing the quality of online videos is to
      provide additional educational health content, such as websites, to support
      health consumers. This study investigates the feasibility of building a content
      based recommender system that links health consumers to reputable health
      educational websites from MedlinePlus for a given health video from YouTube.
      METHODS: The dataset for this study includes a collection of health-related
      videos and their available metadata. Semantic technologies (such as SNOMED-CT and
      Bio-ontology) were used to recommend health websites from MedlinePlus. A total of
      26 healths professionals participated in evaluating 253 recommended links for a
      total of 53 videos about general health, hypertension, or diabetes. The relevance
      of the recommended health websites from MedlinePlus to the videos was measured
      using information retrieval metrics such as the normalized discounted cumulative
      gain and precision at K. RESULTS: The majority of websites recommended by our
      system for health videos were relevant, based on ratings by health professionals.
      The normalized discounted cumulative gain was between 46% and 90% for the
      different topics. CONCLUSIONS: Our study demonstrates the feasibility of using a
      semantic content-based recommender system to enrich YouTube health videos.
      Evaluation with end-users, in addition to healthcare professionals, will be
      required to identify the acceptance of these recommendations in a nonsimulated
      information-seeking context.

PMID- 28506226
TI  - Institutional delivery service utilization and associated factors among women of
      reproductive age in the mobile pastoral community of the Liban District in Guji
      Zone, Oromia, Southern Ethiopia: a cross sectional study.
AB  - BACKGROUND: Globally, an estimated 289,000 maternal deaths occurred in 2013.
      Majority of these deaths occurred in sub-Saharan Africa and Southern Asia.
      Mobility of pastoralists is a well-recognized survival strategy in arid and semi
      arid land of sub-Saharan Africa. However governments often encourage settlement
      as a solution to the difficulty of providing health services for mobile
      pastoralists. This study aimed to assess utilization of institutional delivery
      and associated factors among women of reproductive age in the mobile pastoral
      community of the Liban District in Guji zone, Oromia, Ethiopia. METHODS: A
      Community based cross-sectional survey was conducted among the mobile pastoralist
      community of the Liban District. Seven hundred ninety-one (791) randomly selected
      women, who had birth within the last 2 years preceding the survey, were
      interviewed using a pretested structured questionnaire. Data were entered into
      Epi-Info version 3.5.4 and analyzed by Statistical Package for Social Science
      (SPSS) version 16. Bivariate and multivariate analyses were done. RESULTS: Out of
      791 women who gave birth within the last 2 years preceding the survey, only 110
      (13.9%) gave birth in health institutions. Majority (74.1%) of the women gave
      birth at their home. Ninety-one women (11.5%) gave birth at traditional birth
      attendant's home; assisted by traditional birth attendants. Multiple logistic
      regression shows that women who had readily available cash at the onset of labor
      (aOR 2.79, 95% CI: 1.29-6.25), delivered the birth preceding the most recent
      birth in a health institution (aOR 6.8, 95% CI: 3.44-13.45) and had birth related
      complications during the birth preceding the most recent birth (aOR 1.90, 95% CI:
      1.08-3.36) were more likely to deliver at health institutions. CONCLUSION:
      Majority of the pastoral women seek institutional delivery, only when labor
      related complications are perceived. Mechanisms of alleviating indirect health
      care costs affecting institutional delivery need to be addressed in future
      studies.

PMID- 28506227
TI  - Associations between disc space narrowing, anterior osteophytes and disability in
      chronic mechanical low back pain: a cross sectional study.
AB  - BACKGROUND: Radiographic features of lumbar disc degeneration (LDD) are common
      findings in patients with chronic mechanical low back pain; however, its role in
      disability and intensity of pain is debatable. This study aims to investigate the
      associations of the x-ray features of LDD and lumbar spondylolisthesis with
      severity of disability and intensity of pain. METHODS: A cross-sectional study
      was conducted on 439 patients with chronic mechanical low back pain who attended
      the rheumatology clinic, National Hospital of Sri Lanka, Colombo, from May 2012
      to May 2014. Severity of disability was measured using Modified Oswestry
      Disability Index and intensity of pain was assessed using numeric rating scale (0
      100). X-ray features of LDD (disc space narrowing, anterior osteophytes and
      overall LDD) and spondylolisthesis were assessed in lateral recumbent lumbar x
      rays (L1/L2 to L5/S1) and graded by a consultant radiologist blinded to clinical
      data. Generalised linear model with linear response was used to assess the
      associations of x-ray features of LDD with severity of disability and intensity
      of pain adjusting for age, gender, body mass index and pain radiating into legs.
      RESULTS: Mean age was 48.99 +/- 11.21 and 323 (73.58%) were females. 87 (19.82%)
      were obese. Mean severity of disability was 30.95 +/- 13.67 and mean intensity of
      pain was 45.50 +/- 20.37. 69 (15.72%), 26 (5.92%) and 85 (19.36%) patients had
      grade 2 disc space narrowing, anterior osteophytes and overall LDD, respectively.
      51 (11.62%) patients had lumbar spondylolisthesis. Grade of disc space narrowing
      and overall LDD were not associated with severity of disability or intensity of
      pain. The presence of lumbar spondylolisthesis was associated with severity of
      disability. Female gender and pain radiating into legs were associated with
      severity of disability and intensity of pain. Advancing age was associated with x
      ray features of LDD and lumbar spondylolisthesis. CONCLUSIONS: Lumbar
      spondylolisthesis is associated with severity of disability in patients with
      chronic mechanical low back pain. Associations of x-ray features of LDD with
      severity of disability and intensity of pain are inconclusive. Female gender and
      pain radiating into legs are significant confounders.

PMID- 28506228
TI  - Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat
      syndrome: a multi-center, double-blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: Traditional Chinese medicine (TCM) has a long history in the
      treatment of psoriasis vulgaris. We aimed to evaluate the clinical efficacy and
      safety of Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood
      heat syndrome. METHODS: A multicenter, randomized, double-blind, placebo
      controlled trial was conducted. Participants with psoriasis vulgaris of blood
      heat syndrome were blinded and randomized to receive Pulian ointment or placebo
      ointment twice daily for 4 weeks, with follow-up 8 weeks after treatment.
      Psoriasis Area Severity Index (PASI) scores, severity of each symptom and area of
      skin lesion and quality of life were assessed at baseline, 2 weeks, and 4 weeks.
      Adverse events were recorded during the study. SAS 9.4 software and SPSS 17.0
      software was applied for data analysis. RESULTS: A total of 300 participants with
      psoriasis vulgaris of blood-heat syndrome were assessed for eligibility, and 294
      were randomly assigned to the Pulian ointment and placebo group from six study
      centers. Full analysis set (FAS): after 4 weeks of treatment, there were
      significant differences between groups in PASI score and the separate score of
      skin lesion area, favoring Pulian ointment group (P < 0.05). However, no
      significant differences were observed in scores of scaling, erythema and
      induration/thickness (P > 0.05). Per protocol set (PPS): There was no
      statistically significant difference in PASI score and separate score of each
      symptom and area of skin lesion between two groups (P > 0.05). Quality of life
      measured by Hamilton Anxiety Rating Scale (HAMA) and 36-Item Short Form Health
      Survey (SF-36) improved after treatment in both groups, but there was no
      significant difference between the two groups (P > 0.05). After being followed up
      for 8 weeks, the total relapse rates of the Pulian Ointment group and placebo
      group were 5.88 and 8.45%, respectively, and the difference was not statistically
      significant between the two groups (P > 0.05). No adverse event was observed in
      both groups throughout the study. CONCLUSIONS: Pulian Ointment seems effective
      and well tolerated in improving the PASI score and separate score of skin lesion
      area for patients with psoriasis vulgaris of blood-heat syndrome. Further
      research could build on the current study to explore whether other preparation
      forms and greater intervention intensity are necessary for better therapeutic
      effects. TRIAL REGISTRATION: Chictr.org.cn Identifier ChiCTR-TRC-12002054 .

PMID- 28506229
TI  - Determinants of felt demand for dengue vaccines in the North Caribbean region of
      Colombia.
AB  - BACKGROUND: The increasing burden associated with dengue in Latin America makes
      it essential to understand the community's interest in acquiring vaccines, as an
      input to plan its introduction in endemic regions. The objective of this study is
      to learn the felt demand for dengue vaccines by estimating the willingness to pay
      and its associated factors in endemic communities of the North Caribbean region
      of Colombia. METHODS: A population survey was administered from October to
      December 2015, including 1037 families in 11 municipalities in Colombia. One
      adult per family was interviewed on their perception and history of dengue.
      Participants received a description of four hypothetical scenarios of dengue
      vaccines, administered in a single dose or in 3 doses, with an effectiveness of
      70% for 5 years or 95% for 30 years. The willingness to pay for each one of these
      vaccines was inquired vs. 5 hypothetical prices in Colombian pesos. RESULTS: Most
      participants recognized dengue as a serious disease in children (99.3%) and
      adults (98.6%). 33 (3.2%) of the total respondents reported having suffered
      dengue and 19 (57.6%) of them required hospitalization. The price of the vaccine
      was inversely related to the willingness to pay. In addition, single dose
      vaccines (compared to 3 doses) and one with a protection of 95% for 30 years
      (compared to an effectiveness of 70% for 5 years), were associated with greater
      willingness to pay. Greater willingness to pay was observed among the respondents
      who considered it likely to get the disease, either themselves (OR 1.56; CI 95%
      1.08-2.26) or their children (OR 1.89; CI 95% 1.28-2.81), in the next 5 years.
      The participants who have been diagnosed with dengue also showed greater
      willingness to pay (OR 1.89; CI 95% 1.01-3.54) compared to those who did not have
      this history. CONCLUSION: Factors such as price, number of doses and
      effectiveness can independently influence the decision to purchase a vaccine
      against an endemic disease, such as dengue. Additionally, this study reveals that
      background and perceptions of the disease can affect individuals' interest in
      acquiring this type of preventive interventions.

PMID- 28506230
TI  - Health literacy and primary health care use of ethnic minorities in the
      Netherlands.
AB  - BACKGROUND: In the Netherlands, ethnic minority populations visit their general
      practitioner (GP) more often than the indigenous population. An explanation for
      this association is lacking. Recently, health literacy is suggested as a possible
      explaining mechanism. Internationally, associations between health literacy and
      health care use, and between ethnicity and health literacy have been studied
      separately, but, so far, have not been linked to each other. In the Netherlands,
      some expectations have been expressed with regard to supposed low health literacy
      of ethnic minority groups, however, no empirical study has been done so far. The
      objectives of this study are therefore to acquire insight into the level of
      health literacy of ethnic minorities in the Netherlands and to examine whether
      the relationship between ethnicity and health care use can be (partly) explained
      by health literacy. METHODS: A questionnaire was sent to a sample of 2.116
      members of the Dutch Health Care Consumer Panel (response rate 46%, 89
      respondents of non-western origin). Health literacy was measured with the Health
      Literacy Questionnaire (HLQ) which covers nine different domains. The health
      literacy levels of ethnic minority groups were compared to the indigenous
      population. A negative binomial regression model was used to estimate the
      association between ethnicity and GP visits. To examine whether health literacy
      is an explaining factor in this association, health literacy and interaction
      terms of health literacy and ethnicity were added into the model. RESULTS:
      Differences in levels of health literacy were only found between the Turkish
      population and the indigenous Dutch population. This study also found an
      association between ethnicity and GP visits. Ethnic minorities visit their GP 33%
      more often than the indigenous population. Three domains of the HLQ (the ability
      to navigate the health care system, the ability to find information and to read
      and understand health information) partly explained the association between
      ethnicity and GP visits. CONCLUSIONS: In general, there are no differences in
      health literacy between most of the ethnic minority groups in the Netherlands and
      the indigenous Dutch population. Only the Turkish population scored significantly
      lower on several health literacy domains. Some domains of health literacy do
      explain the association between ethnicity and higher frequency of GP visits.
      Further research is recommended to understand the pathways through which health
      literacy impacts health care use.

PMID- 28506231
TI  - Optogenetic interrogation reveals separable G-protein-dependent and -independent
      signalling linking G-protein-coupled receptors to the circadian oscillator.
AB  - BACKGROUND: Endogenous circadian oscillators distributed across the mammalian
      body are synchronised among themselves and with external time via a variety of
      signalling molecules, some of which interact with G-protein-coupled receptors
      (GPCRs). GPCRs can regulate cell physiology via pathways originating with
      heterotrimeric G-proteins or beta-arrestins. We applied an optogenetic approach
      to determine the contribution of these two signalling modes on circadian phase.
      RESULTS: We employed a photopigment (JellyOp) that activates Galphas signalling
      with better selectivity and higher sensitivity than available alternatives, and a
      point mutant of this pigment (F112A) biased towards beta-arrestin signalling.
      When expressed in fibroblasts, both native JellyOp and the F112A arrestin-biased
      mutant drove light-dependent phase resetting in the circadian clock. Shifts
      induced by the two opsins differed in their circadian phase dependence and the
      degree to which they were associated with clock gene induction. CONCLUSIONS: Our
      data imply separable G-protein and arrestin inputs to the mammalian circadian
      clock and establish a pair of optogenetic tools suitable for manipulating Galphas
      and beta-arrestin-biased signalling in live cells.

PMID- 28506232
TI  - Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the
      embryonic mouse cerebral cortex.
AB  - BACKGROUND: During the development of the mammalian cerebral cortex, newborn
      postmitotic projection neurons are born from local neural stem cells and must
      undergo radial migration so as to position themselves appropriately to form
      functional neural circuits. The zinc finger transcriptional repressor Rp58 (also
      known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its
      underlying molecular mechanism remains to be better characterised. FINDINGS:
      Here, we demonstrate that the co-expression of Rp58 and the cyclin dependent
      kinase inhibitor (CDKI) p27kip1 is important for E14.5-born cortical neurons to
      coordinate cell cycle exit and initiate their radial migration. Notably, we find
      that the impaired radial positioning of Rp58-deficient cortical neurons within
      the embryonic (E17.5) mouse cortex, as well as their multipolar to bipolar
      transition from the intermediate zone to the cortical plate can be restored by
      forced expression of p27kip1 in concert with suppression of Rnd2, a downstream
      target gene of Rp58. Furthermore, the restorative effects of p27kip1 and Rnd2
      abrogation are reminiscent of suppressing RhoA signalling in Rp58-deficient
      cells. CONCLUSIONS: Our findings demonstrate functional interplay between a
      transcriptional regulator and a CDKI to mediate neuroprogenitor cell cycle exit,
      as well as to promote radial migration through a molecular mechanism consistent
      with suppression of RhoA signalling.

PMID- 28506233
TI  - Measurement and decomposition of socioeconomic inequality in single and
      multimorbidity in older adults in China and Ghana: results from the WHO study on
      global AGEing and adult health (SAGE).
AB  - BACKGROUND: Globally people are living longer and enduring non-communicable
      diseases (NCDs) many of which co-occur as multimorbidity. Demographic and
      socioeconomic factors are determinants of inequalities and inequities in health.
      There is a need for country-specific evidence of NCD inequalities in developing
      countries where populations are ageing rapidly amid economic and social change.
      The study measures and decomposes socioeconomic inequality in single and multiple
      NCD morbidity in adults aged 50 and over in China and Ghana. METHODS: The data
      source is the World Health Organization Study on Global AGEing and Adult Health
      (SAGE) Wave 1 (2007-2010). Nationally representative cross-sectional data
      collected from adults in China (n = 11,814) and Ghana (n = 4,050) are analysed.
      Country populations are ranked by a socioeconomic index based on ownership of
      household assets. The study uses a decomposed concentration index (CI) of single
      and multiple NCD morbidity (multimorbidity) covering arthritis, diabetes, angina,
      stroke, asthma, depression, chronic lung disease and hypertension. The CI
      quantifies the extent of overall inequality on each morbidity measure. The
      decomposition utilises a regression-based approach to examine individual
      contributions of demographic and socioeconomic factors, or determinants, to the
      overall inequality. RESULTS: In China, the prevalence of single and multiple NCD
      morbidity was 64.7% and 53.4%, compared with 65.9% and 55.5% respectively in
      Ghana. Inequalities were significant and more highly concentrated among the poor
      in China (single morbidity CI = -0.0365: 95% CI = -0.0689,-0.0040; multimorbidity
      CI = -0.0801: 95% CI = -0.1233,-0.0368;). In Ghana inequalities were significant
      and more highly concentrated among the rich (single morbidity CI = 0.1182; 95% CI
      = 0.0697, 0.1668; multimorbidity CI = 0.1453: 95% CI = 0.0794, 0.2083). In China,
      rural residence contributed most to inequality in single morbidity (36.4%) and
      the wealth quintiles contributed most to inequality in multimorbidity (39.0%). In
      Ghana, the wealth quintiles contributed 24.5% to inequality in single morbidity
      and body mass index contributed 16.2% to the inequality in multimorbidity.
      CONCLUSIONS: The country comparison reflects different stages of economic
      development and social change in China and Ghana. More studies of this type are
      needed to inform policy-makers about the patterning of socioeconomic inequalities
      in health, particularly in developing countries undergoing rapid epidemiological
      and demographic transitions.

PMID- 28506235
TI  - Single-staged uniportal VATS in the supine position for simultaneous bilateral
      primary spontaneous pneumothorax.
AB  - BACKGROUND: Simultaneous bilateral primary spontaneous pneumothorax (SBPSP) is
      rare, but requires surgery on both sides, in patients with definite bilateral
      bullae to prevent life-threatening conditions. Recently, uniportal video-assisted
      thoracoscopic surgery (VATS) has been widely accepted as a less invasive
      technique for the treatment of pneumothorax. Thus, we introduced single-staged
      uniportal VATS technique in the supine position, for the management of two cases
      of SBPSP. CASE PRESENTATION: A 17-year-old boy presented with bilateral
      spontaneous pneumothorax and he underwent single-staged uniportal VATS in the
      supine position. Single wide draping in consecutive bilateral approaches removes
      the needs of changing patients' position. Whole thoracoscopic procedure for wedge
      resection of bullae lesions was conducted without difficulty. The total operation
      time took 65 min and the patient discharged 3 days after the operation. The
      patient was followed for 24 months without recurrence of both sides. Another 18
      year-old boy was admitted with bilateral spontaneous pneumothorax and single
      staged uniportal VATS was also performed in the supine position. The total
      operation time took 79 min and the patient discharged on postoperative day 4. He
      was followed for 19 months without recurrence of both sides. CONCLUSIONS: Single
      staged uniportal VATS approach yielded satisfactory results from simplicity that
      not requires position change compared to conventional multi-ports VATS in the
      lateral position, and with better cosmetics. This technique is thought to be a
      feasible procedure in selective patients with SBPSP or with contralateral bullae
      for preventive role.

PMID- 28506236
TI  - Knowing where the nose is.
AB  - Improvements in imaging technology and the development of powerful machine
      learning algorithms are revolutionizing the study of animal behavior in the
      laboratory. These innovations promise to reveal both global and local features of
      action relevant to understanding how the brain functions. A study in BMC Biology
      describes one such tool called OptiMouse, which is an open source platform that
      uses video to capture key features of mouse behavior, including information
      relevant to olfactory investigation.See research article: 10.1186/s12915-017-0377
      3.

PMID- 28506234
TI  - Anti-malarial medicine quality field studies and surveys: a systematic review of
      screening technologies used and reporting of findings.
AB  - BACKGROUND: Assessing the quality of medicines in low-middle income countries
      (LMICs) relies primarily on human inspection and screening technologies, where
      available. Field studies and surveys have frequently utilized screening tests to
      analyse medicines sampled at the point of care, such as health care facilities
      and medicine outlets, to provide a snap shot of medicine quality in a specific
      geographical area. This review presents an overview of the screening tests
      typically employed in surveys to assess anti-malarial medicine quality,
      summarizes the analytical methods used, how findings have been reported and
      proposes a reporting template for future studies. METHODS: A systematic search of
      the peer-reviewed and grey literature available in the public domain (including
      national and multi-national medicine quality surveys) covering the period 1990
      2016 was undertaken. Studies were included if they had used screening techniques
      to assess the quality of anti-malarial medicines. As no standardized set of
      guidelines for the methodology and reporting of medicine quality surveys exist,
      the included studies were assessed for their standard against a newly proposed
      list of criteria. RESULTS: The titles and abstracts of 4621 records were screened
      and only 39 were found to meet the eligibility criteria. These 39 studies
      utilized visual inspection, disintegration, colorimetry and Thin Layer
      Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF)
      MiniLab(r) or as individual tests. Overall, 30/39 studies reported employing
      confirmatory testing described in international pharmacopeia to verify the
      quality of anti-malarials post assessment by a screening test. The authors
      assigned scores for the 23 criteria for the standard of reporting of each study.
      CONCLUSIONS: There is considerable heterogeneity in study design and
      inconsistency in reporting of field surveys of medicine quality. A lack of
      standardization in the design and reporting of studies of medicine quality
      increases the risk of bias and error, impacting on the generalizability and
      reliability of study results. The criteria proposed for reporting on the standard
      of studies in this review can be used in conjunction with existing medicine
      quality survey guidelines as a checklist for designing and reporting findings of
      studies. The review protocol has been registered with PROSPERO (CRD42015026782).

PMID- 28506237
TI  - Clinical and MRI outcome of cervical spine lesions in children with juvenile
      idiopathic arthritis treated with anti-TNFalpha drugs early in disease course.
AB  - BACKGROUNDS: The purpose of the study was to evaluate the clinical and magnetic
      resonance imaging (MRI) outcome of cervical spine arthritis in children with
      juvenile idiopathic arthritis (JIA), who received anti-TNFalpha early in the
      course of cervical spine arthritis. METHODS: Medical charts and imaging of JIA
      patients with cervical spine involvement were reviewed in this retrospective
      study. Data, including age at disease onset, JIA type, disease activity,
      treatment and clinical outcome were collected. Initial and followup MRI
      examinations of cervical spine were performed according to the hospital protocol
      to evaluate the presence of inflammation and potential chronic/late changes.
      RESULTS: Fifteen JIA patients with MRI proved cervical spine inflammation (11
      girls, 4 boys, median age 6.3y) were included in the study: 9 had polyarthritis,
      3 extended oligoarthritis, 2 persistent oligoarthritis and 1 juvenile psoriatic
      arthritis. All children were initially treated with high-dose steroids and
      methotrexate. In addition, 11 patients were treated with anti-TNFalpha drug
      within 3 months, and 3 patients within 7 months of cervical spine involvement
      confirmed by MRI. Mean observation time was 2.9y, mean duration of anti-TNFalpha
      treatment was 2.2y. Last MRI showed no active inflammation in 12/15 children,
      allowing to stop biological treatment in 3 patients, and in 3/15 significant
      reduction of inflammation. Mild chronic changes were found on MRI in 3 children.
      CONCLUSIONS: Early treatment with anti-TNFalpha drugs resulted in significantly
      reduced inflammation or complete remission of cervical spine arthritis proved by
      MRI, and prevented the development of serious chronic/late changes. Repeated MRI
      examinations are suggested in the follow-up of JIA patients with cervical spine
      arthritis.

PMID- 28506238
TI  - Ten-year survival rate after rotational acetabular osteotomy in adulthood hip
      dysplasia.
AB  - BACKGROUND: Rotational acetabular osteotomy (RAO) is an effective joint
      preserving surgical treatment for adulthood hip dysplasia (AHD). Despite
      sufficient correction of acetabular dysplasia, some patients still experience
      osteoarthritis (OA) progression and require total hip arthroplasty (THA). The
      purposes of the current study were to investigate the survival rate and the risk
      factors for OA progression or THA requirement after RAO and to explore whether
      acetabular overcorrection relates to OA progression. METHODS: Fifty-six patients
      (65 hips, mean age: 36.5 +/- 11.7 years) with AHD who underwent RAO and were
      followed up for >10 years (mean: 15.0 +/- 3.2 years) were enrolled in this study.
      A Kaplan-Meier survival analysis was performed to assess the non-OA progression
      rate and THA-free survival rate of RAO during the 10-year follow-up. To analyze
      the risk factors for OA progression and THA requirement, the Cox proportional
      hazards regression analysis was performed. RESULTS: No OA progression was found
      in 76.7% of the patients, and THA was not required in 92.3% during the 10-year
      follow-up. By multivariate regression analysis, older age at the time of surgery
      was a risk factor for both OA progression (hazard ratio [HR] = 1.047, 95%
      confidence interval [CI] = 1.005-1.091) and THA requirement (HR = 1.293, 95% CI =
      1.041-1.606). CONCLUSION: RAO is an effective surgical procedure for symptomatic
      patients with AHD that prevents OA progression and protects the hips from
      undergoing THA. However, older patients have a higher risk for both OA
      progression and THA requirement.

PMID- 28506239
TI  - Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer.
AB  - BACKGROUND: Patients with metastatic or relapsed gallbladder cancer generally
      have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic
      strategies to treat gallbladder cancer. METHODS: Levels of translationally
      controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by
      immunohistochemical staining. Wound healing, migration and invasion assays were
      used to investigate the motility of cells. Western blot assay was used to
      investigate the levels of TCTP and other proteins. Liver metastasis models and
      lung metastasis models were established to investigate the inhibitory effect of
      Dihydroartemisinin on gallbladder cancer metastasis. RESULTS: TCTP is aberrantly
      expressed in gallbladder cancer patients and associated with metastasis and a
      poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell
      migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of
      TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell
      division control protein 42 homolog (Cdc42) activation. In addition, in mice with
      xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder
      cancer cell metastases and improved survival. CONCLUSIONS: These findings provide
      new insights into the therapeutic activity of Dihydroartemisinin as a treatment
      for gallbladder cancer metastasis.

PMID- 28506240
TI  - Inhibitors compounds of the flavivirus replication process.
AB  - Flaviviruses are small viruses with single-stranded RNA, which include the yellow
      fever virus, dengue virus, West Nile virus, Japanese encephalitis virus, tick
      borne encephalitis virus, and Zika virus; and are causal agents of the most
      important emerging diseases that have no available treatment to date. In recent
      years, the strategy has focused on the development of replication inhibitors of
      these viruses designed to act mainly by affecting the activity of enzyme
      proteins, such as NS3 and NS5, which perform important functions in the viral
      replication process. This article describes the importance of flaviviruses and
      the development of molecules used as inhibitors of viral replication in this
      genus.

PMID- 28506241
TI  - Socio-demographic determinants of Toxoplasma gondii seroprevalence in migrant
      workers of Peninsular Malaysia.
AB  - BACKGROUND: The number of migrants working in Malaysia has increased sharply
      since the 1970's and there is concern that infectious diseases endemic in other
      (e.g. neighbouring) countries may be inadvertently imported. Compulsory medical
      screening prior to entering the workforce does not include parasitic infections
      such as toxoplasmosis. Therefore, this study aimed to evaluate the seroprevalence
      of T. gondii infection among migrant workers in Peninsular Malaysia by means of
      serosurveys conducted on a voluntary basis among low-skilled and semi-skilled
      workers from five working sectors, namely, manufacturing, food service,
      agriculture and plantation, construction and domestic work. METHODS: A total of
      484 migrant workers originating from rural locations in neighbouring countries,
      namely, Indonesia (n = 247, 51.0%), Nepal (n = 99, 20.5%), Bangladesh (n = 72,
      14.9%), India (n = 52, 10.7%) and Myanmar (n = 14, 2.9%) were included in this
      study. RESULTS: The overall seroprevalence of T. gondii was 57.4% (n = 278; 95%
      CI: 52.7-61.8%) with 52.9% (n = 256; 95% CI: 48.4-57.2%) seropositive for anti
      Toxoplasma IgG only, 0.8% (n = 4; 95% CI: 0.2-1.7%) seropositive for anti
      Toxoplasma IgM only and 3.7% (n = 18; 95% CI: 2.1-5.4%) seropositive with both
      IgG and IgM antibodies. All positive samples with both IgG and IgM antibodies
      showed high avidity (> 40%), suggesting latent infection. Age (being older than
      45 years), Nepalese nationality, manufacturing occupation, and being a newcomer
      in Malaysia (excepting domestic work) were positively and statistically
      significantly associated with seroprevalence (P < 0.05). CONCLUSIONS: The results
      of this study suggest that better promotion of knowledge about parasite
      transmission is required for both migrant workers and permanent residents in
      Malaysia. Efforts should be made to encourage improved personal hygiene before
      consumption of food and fluids, thorough cooking of meat and better disposal of
      feline excreta from domestic pets.

PMID- 28506243
TI  - Cost analysis of the very elderly admitted to intensive care units.
AB  - BACKGROUND: Very elderly patients are often admitted to intensive care units
      (ICUs) despite poor outcomes and frequent preference to avoid unnecessary
      prolongation of life. We sought to determine the cost of ICU admission for the
      very elderly and the factors influencing this cost. METHODS: This prospective,
      observational cohort study included patients >=80 years old admitted to 22
      Canadian ICUs from 2009 to 2013. A subset of consenting individuals comprised a
      longitudinal cohort followed over 12 months. Costs were calculated from ICU
      length of stay and unit costs for ICU admission from a Canadian academic
      hospital. A generalized linear model was employed to identify cost-predictive
      variables. RESULTS: In total, 1671 patients were included; 610 were enrolled in
      the longitudinal cohort. The average age was 85 years; median ICU length of stay
      was 4 days. Mortality was 35% (585/1671) in hospital and 41% (253/610) at 12
      months. The average cost of ICU admission per patient was $31,679 +/- 65,867.
      Estimated ICU costs were $48,744 per survivor to discharge and $61,783 per
      survivor at 1 year. For both decedents and survivors, preference for comfort
      measures over life support was an independent predictor for lower cost (P <
      0.01). CONCLUSIONS: Considering the poor clinical outcomes, and that many ICU
      admissions may be undesired by very elderly patients, ICU costs in this
      population are substantial. Our finding that a preference for comfort care
      predicted a lower cost independent of mortality reinforces the importance of
      early goals of care discussions to avoid both undesired and potentially non
      beneficial interventions, consequently reducing costs. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01293708 . Registered on 10 February 2011.

PMID- 28506242
TI  - An imprinted non-coding genomic cluster at 14q32 defines clinically relevant
      molecular subtypes in osteosarcoma across multiple independent datasets.
AB  - BACKGROUND: A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has
      been associated with outcome in osteosarcoma. We assessed the clinical utility of
      this miRNA set and their association with methylation status. METHODS: We
      integrated coding and non-coding RNA data from three independent annotated
      clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and
      methylation data from one in vitro (19 cell lines) and one clinical (NCI
      Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
      osteosarcoma dataset, n = 80) dataset. We used time-dependent receiver operating
      characteristic (tdROC) analysis to evaluate the clinical value of candidate miRNA
      profiles and machine learning approaches to compare the coding and non-coding
      transcriptional programs of high- and low-risk osteosarcoma tumors and high-
      versus low-aggressiveness cell lines. In the cell line and TARGET datasets, we
      also studied the methylation patterns of the MEG3 imprinting control region on
      14q32 and their association with miRNA expression and tumor aggressiveness.
      RESULTS: In the tdROC analysis, miRNA sets on 14q32 showed strong discriminatory
      power for recurrence and survival in the three clinical datasets. High- or low
      risk tumor classification was robust to using different microRNA sets or
      classification methods. Machine learning approaches showed that genome-wide miRNA
      profiles and miRNA regulatory networks were quite different between the two
      outcome groups and mRNA profiles categorized the samples in a manner concordant
      with the miRNAs, suggesting potential molecular subtypes. Further, miRNA
      expression patterns were reproducible in comparing high-aggressiveness versus low
      aggressiveness cell lines. Methylation patterns in the MEG3 differentially
      methylated region (DMR) also distinguished high-aggressiveness from low
      aggressiveness cell lines and were associated with expression of several 14q32
      miRNAs in both the cell lines and the large TARGET clinical dataset. Within the
      limits of available CpG array coverage, we observed a potential methylation
      sensitive regulation of the non-coding RNA cluster by CTCF, a known enhancer
      blocking factor. CONCLUSIONS: Loss of imprinting/methylation changes in the 14q32
      non-coding region defines reproducible previously unrecognized osteosarcoma
      subtypes with distinct transcriptional programs and biologic and clinical
      behavior. Future studies will define the precise relationship between 14q32
      imprinting, non-coding RNA expression, genomic enhancer binding, and tumor
      aggressiveness, with possible therapeutic implications for both early- and
      advanced-stage patients.

PMID- 28506244
TI  - Early EEG for outcome prediction of postanoxic coma: prospective cohort study
      with cost-minimization analysis.
AB  - BACKGROUND: We recently showed that electroencephalography (EEG) patterns within
      the first 24 hours robustly contribute to multimodal prediction of poor or good
      neurological outcome of comatose patients after cardiac arrest. Here, we confirm
      these results and present a cost-minimization analysis. Early prognosis
      contributes to communication between doctors and family, and may prevent
      inappropriate treatment. METHODS: A prospective cohort study including 430
      subsequent comatose patients after cardiac arrest was conducted at intensive care
      units of two teaching hospitals. Continuous EEG was started within 12 hours after
      cardiac arrest and continued up to 3 days. EEG patterns were visually classified
      as unfavorable (isoelectric, low-voltage, or burst suppression with identical
      bursts) or favorable (continuous patterns) at 12 and 24 hours after cardiac
      arrest. Outcome at 6 months was classified as good (cerebral performance category
      (CPC) 1 or 2) or poor (CPC 3, 4, or 5). Predictive values of EEG measures and
      cost-consequences from a hospital perspective were investigated, assuming EEG
      based decision- making about withdrawal of life-sustaining treatment in the case
      of a poor predicted outcome. RESULTS: Poor outcome occurred in 197 patients (51%
      of those included in the analyses). Unfavorable EEG patterns at 24 hours
      predicted a poor outcome with specificity of 100% (95% CI 98-100%) and
      sensitivity of 29% (95% CI 22-36%). Favorable patterns at 12 hours predicted good
      outcome with specificity of 88% (95% CI 81-93%) and sensitivity of 51% (95% CI 42
      60%). Treatment withdrawal based on an unfavorable EEG pattern at 24 hours
      resulted in a reduced mean ICU length of stay without increased mortality in the
      long term. This gave small cost reductions, depending on the timing of
      withdrawal. CONCLUSIONS: Early EEG contributes to reliable prediction of good or
      poor outcome of postanoxic coma and may lead to reduced length of ICU stay. In
      turn, this may bring small cost reductions.

PMID- 28506245
TI  - Comparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western
      blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis.
AB  - BACKGROUND: Currently, the reference standard assay for the serodiagnosis of
      neurocysticercosis (NCC) is the lentil lectin-bound glycoproteins/enzyme-linked
      immunoelectrotransfer blot (LLGP-EITB). The main disadvantage of this technique
      is the complexity of obtaining and purifying the LLGP extract. This could be
      solved by replacement with highly specific recombinant antigens from Taenia
      solium. Based on previous studies, we selected and produced the recombinant Ts8B2
      and T24H proteins and applied them to three diagnostic techniques: western blot
      (WB), enzyme-linked immunosorbent assay (ELISA) and the multiplex bead-based
      assay (MBA). METHODS: The Ts8B2 and T24H cDNA sequences were expressed in a
      prokaryotic system and the corresponding expression products purified; three
      recombinant proteins were further characterized: T24H-his, GST-T24H and GST
      Ts8B2. The proteins on WB, ELISA and MBA were tested against 149 sera from
      patients with NCC confirmed by brain imaging, 40 sera from patients with other
      parasitic diseases, and 131 sera from US. individuals without evidence of
      neurocysticercosis (clinical/serological/brain imaging). The sensitivity and
      specificity of each antigen by WB were calculated by counting the number of true
      positive, false positive, true negative and false negative results. Using the
      receiver operating characteristic (ROC) curves, the cut-off values for the ELISA
      and MBA were established as well as the sensitivity and specificity of each
      assay. RESULTS: All three antigens showed a high sensitivity on WB in active NCC
      cases with two or more viable cysts and low sensitivity for cases with single
      viable cyst or calcified lesions and inactive NCC. WB showed the highest
      specificity and sensitivity out of the three diagnostic techniques. The
      recombinant T24H-his was the best diagnostic reagent in WB (100% sensitivity,
      99.4% specificity), exhibiting similar results to the LLGP-EITB, against the same
      panel of NCC sera. The GST-T24H antigen worked better than the others in ELISA
      and MBA protocols (88.3 and 96.1% sensitivity, respectively and 96.5%
      specificity). CONCLUSIONS: The sensitivity and specificity that we obtained were
      similar to results from a previous study using a similar recombinant antigen
      (rT24H), suggesting that recombinant antigens may be good alternatives to crude
      extracts in a variety of diagnostic techniques. Furthermore, these antigens can
      be applied in the development of point-of-care tests which would be useful in NCC
      field studies.

PMID- 28506247
TI  - Erratum to: Evaluation of a technology-enhanced integrated care model for frail
      older persons: protocol of the SPEC study, a stepped-wedge cluster randomized
      trial in nursing homes.

PMID- 28506246
TI  - Vipie: web pipeline for parallel characterization of viral populations from
      multiple NGS samples.
AB  - BACKGROUND: Next generation sequencing (NGS) technology allows laboratories to
      investigate virome composition in clinical and environmental samples in a culture
      independent way. There is a need for bioinformatic tools capable of parallel
      processing of virome sequencing data by exactly identical methods: this is
      especially important in studies of multifactorial diseases, or in parallel
      comparison of laboratory protocols. RESULTS: We have developed a web-based
      application allowing direct upload of sequences from multiple virome samples
      using custom parameters. The samples are then processed in parallel using an
      identical protocol, and can be easily reanalyzed. The pipeline performs de-novo
      assembly, taxonomic classification of viruses as well as sample analyses based on
      user-defined grouping categories. Tables of virus abundance are produced from
      cross-validation by remapping the sequencing reads to a union of all observed
      reference viruses. In addition, read sets and reports are created after
      processing unmapped reads against known human and bacterial ribosome references.
      Secured interactive results are dynamically plotted with population and diversity
      charts, clustered heatmaps and a sortable and searchable abundance table.
      CONCLUSIONS: The Vipie web application is a unique tool for multi-sample
      metagenomic analysis of viral data, producing searchable hits tables, interactive
      population maps, alpha diversity measures and clustered heatmaps that are grouped
      in applicable custom sample categories. Known references such as human genome and
      bacterial ribosomal genes are optionally removed from unmapped ('dark matter')
      reads. Secured results are accessible and shareable on modern browsers. Vipie is
      a freely available web-based tool whose code is open source.

PMID- 28506248
TI  - Paraquat and Parkinson's disease: a systematic review protocol according to the
      OHAT approach for hazard identification.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition
      that has genetic susceptibility, aging, and exposure to certain chemicals as risk
      factors. In recent decades, epidemiological and experimental studies have
      investigated the role of pesticides in the development of PD, in particular that
      of the herbicide paraquat. Here, we, therefore, aim to systematically review the
      association between paraquat exposure and PD. METHODS: Observational studies
      (cohort, case-control, and cross-sectional) eligible for this systematic review
      will enroll any participant who was occupationally and/or environmentally exposed
      to paraquat. Experimental studies, including in vivo and in vitro assays designed
      to assess neurotoxicological endpoints or mechanisms of paraquat neurotoxicity,
      will also be eligible. Outcomes of interest include the following: PD diagnosis;
      neurobehavioral, biochemical, and/or morphological alterations; and cellular,
      biochemical, and/or molecular pathways to oxidative stress. Using terms to
      include all forms of paraquat combined with PD, the following electronic
      databases will be searched: PubMed, EMBASE, LILACS, Toxnet, and Web of Science,
      without restrictions as to language, year, or status of publication. A team of
      reviewers will independently select potential titles and abstracts, extract data,
      assess risk of bias, and determine the overall quality of evidence for each
      outcome using the Office of Health Assessment and Translation (OHAT) approach for
      systematic reviews and evidence integration. Dichotomous data will be summarized
      as odds ratios, and continuous data will be given as mean differences, both with
      their respective 95% confidence intervals. DISCUSSION: This is the first time
      that the OHAT systematic review protocol will be applied to investigate a
      possible causal association between exposure to paraquat and PD. Results from
      this study could serve as basis for regulatory agencies to define paraquat levels
      of concern, supporting its risk assessment process. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42016050861.

PMID- 28506249
TI  - An unusual case of proximal humeral simple bone cyst in an adult from secondary
      cystic change.
AB  - BACKGROUND: Simple bone cysts (SBC) have been documented to occur in adults with
      closed physeal plates, most commonly affecting the calcaneus in this patient
      subset. Although most authors theorize an association to trauma, etiology of
      simple bone cysts remains an enigma up to now. CASE PRESENTATION: A 26-year-old
      kickboxing coach sought consult for a painful right shoulder which on radiographs
      and magnetic resonance (MR) imaging showed a proximal humeral lesion with signs
      of ossification. The patient was lost to follow-up but again sought consult after
      3 years for the recurring complaint. On repeat radiographs, computed tomography
      (CT) scan, and MR images, tumor enlargement with cystic findings typical of
      simple bone cyst were documented. Diagnostic aspiration of the lesion was firstly
      done, revealing straw-colored fluid. The patient then underwent intralesional
      curettage with alpha-tricalcium phosphate cement reconstruction of the lytic
      defect. No perioperative complications were incurred, and on latest follow-up at
      3 years postoperatively, Musculoskeletal Tumor Society (MSTS) and visual analog
      scale (VAS) pain scores were 30/30 and 0/10, respectively. CONCLUSIONS: The
      authors believe their report provides support to a possible association to trauma
      of simple bone cysts occurring in the adult population with closed physes and
      suggest this subset of patients may require a different treatment approach from
      that for juvenile simple bone cysts.

PMID- 28506250
TI  - Antimicrobial resistance profile of staphylococcus aureus isolates isolated from
      ear discharges of patients at University of Hawassa comprehensive specialized
      hospital.
AB  - BACKGROUND: Drug-resistant microorganism are a growing global danger. Strains of
      S. aureus have developed resistance to many commonly used antimicrobials due to
      indiscriminate use of antimicrobials, and treatment becoming a challenge. Studies
      assessing pattern and determinants of S. aureus resistance in ear infection in
      Ethiopia are very scarce. This study presents overview of pattern and
      determinants S. aureus resistance from samples of ear discharge in Ethiopia.
      METHOD: A prospective cross-sectional study was conducted on patients who visit
      ENT clinic of University of Hawassa comprehensive specialized hospital from
      February 1, 2016 to November 1, 2016. 117 specimens were collected with sterile
      applicator cotton swab from 117 patients with ear discharge visiting the clinic.
      Data was fed and then edited, cleared, entered and analyzed using SPSS version
      20. RESULT: The prevalence of S.aureus infection was 28.2%. S. aureus isolates
      revealed up to 97.0% level of resistance pattern to the antimicrobials tested. In
      the determination of the susceptibility of S. aureus on nine selected antibiotics
      by disk diffusion technique, 97.0% of the isolates were resistant to cloxacilin
      and 74.2% showed resistance to vancomycin. The overall rate of MDR was 100%, all
      of the isolates were found to be resistant to more than two tested
      antimicrobials. CONCLUSION: S. aureus has gotten frighteningly resistant to many
      of common antimicrobials. Resistance rate to vancomyin is terrifyingly high. It
      urges us to take measures to delay resistance. Emergence of resistance highlights
      the value of prudent prescribing of antimicrobials and avoiding their irrational
      use. Further researches focusing on identifying dynamics promoting resistance,
      identifying high risk strains and molecular basis of resistance are required.

PMID- 28506252
TI  - The impact of residential status on cognitive decline among older adults in
      China: Results from a longitudinal study.
AB  - BACKGROUND: Residential status has been linked to numerous determinants of health
      and well-being. However, the influence of residential status on cognitive decline
      remains unclear. The purpose of this research was to assess the changes of
      cognitive function among older adults with different residential status (urban
      residents, rural-to-urban residents, rural residents, and urban-to-rural
      residents), over a 12-year period. METHODS: We used five waves of data (2002,
      2005, 2008/2009, 2011/2012, and 2014) from the Chinese Longitudinal Healthy
      Longevity Survey with 17,333 older adults age 65 and over who were interviewed up
      to five times. Cognitive function was measured by the Mini Mental State
      Examination (MMSE). Multilevel models were used regarding the effects of
      residential status after adjusting for demographic characteristics, socioeconomic
      factors, family support, health behaviors, and health status. RESULTS: After
      controlling for covariates, significant differences in cognitive function were
      found across the four groups: rural-to-urban and rural residents had a higher
      level of cognition than urban residents at baseline. On average, cognitive
      function decreased over the course of the study period. Rural-to-urban and rural
      residents demonstrated a faster decline in cognitive function than urban
      residents. CONCLUSIONS: This study suggests that residential status has an impact
      on the rate of changes in cognition among older adults in China. Results from
      this study provide directions for future research that addresses health
      disparities, particularly in countries that are undergoing significant
      socioeconomic transitions.

PMID- 28506251
TI  - Diversity, in-vitro virulence traits and antifungal susceptibility pattern of
      gastrointestinal yeast flora of healthy poultry, Gallus gallus domesticus.
AB  - BACKGROUND: Poultry farming and consumption of poultry (Gallus gallus domesticus)
      meat and eggs are common gastronomical practices worldwide. Till now, a detailed
      understanding about the gut colonisation of Gallus gallus domesticus by yeasts
      and their virulence properties and drug resistance patterns in available
      literature remain sparse. This study was undertaken to explore this prevalent
      issue. RESULTS: A total of 103 specimens of fresh droppings of broiler chickens
      (commercial G domesticus) and domesticated chickens (domesticated G domesticus)
      were collected from the breeding sites. The isolates comprised of 29 (33%)
      Debaryozyma hansenii (Candida famata), 12 (13.6%) Sporothrix catenata (C.
      ciferrii), 10 (11.4%) C. albicans, 8 (9.1%) Diutnia catenulata (C. catenulate), 6
      (6.8%) C. tropicalis, 3 (3.4%) Candida acidothermophilum (C. krusei), 2 (2.3%) C.
      pintolopesii, 1 (1.1%) C. parapsilosis, 9 (10.2%) Trichosporon spp. (T.
      moniliiforme, T. asahii), 4 (4.5%) Geotrichum candidum, 3 (3.4%) Cryptococcus
      macerans and 1 (1%) Cystobasidium minuta (Rhodotorula minuta). Virulence factors,
      measured among different yeast species, showed wide variability. Biofilm cells
      exhibited higher Minimum Inhibitory Concentration (MIC) values (MUg/ml) than
      planktonic cells against all antifungal compounds tested: (fluconazole, 8-512 vs
      0.031-16; amphotericin B, 0.5-64 vs 0.031-16; voriconazole 0.062-16 vs 0.062-8;
      caspofungin, 0.062-4 vs 0.031-1). CONCLUSIONS: The present work extends the
      current understanding of in vitro virulence factors and antifungal susceptibility
      pattern of gastrointestinal yeast flora of G domesticus. More studies with
      advanced techniques are needed to quantify the risk of spread of these potential
      pathogens to environment and human.

PMID- 28506253
TI  - Genome-wide identification of lncRNAs associated with chlorantraniliprole
      resistance in diamondback moth Plutella xylostella (L.).
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) are now considered important regulatory
      factors, with a variety of biological functions in many species including
      insects. Some lncRNAs have the ability to show rapid responses to diverse stimuli
      or stress factors and are involved in responses to insecticide. However, there
      are no reports to date on the characterization of lncRNAs associated with
      chlorantraniliprole resistance in Plutella xylostella. RESULTS: Nine RNA
      libraries constructed from one susceptible (CHS) and two chlorantraniliprole
      resistant P. xylostella strains (CHR, ZZ) were sequenced, and 1309 lncRNAs were
      identified, including 877 intergenic lncRNAs, 190 intronic lncRNAs, 76 anti-sense
      lncRNAs and 166 sense-overlapping lncRNAs. Of the identified lncRNAs, 1059 were
      novel. Furthermore, we found that 64 lncRNAs were differentially expressed
      between CHR and CHS and 83 were differentially expressed between ZZ and CHS, of
      which 22 were differentially expressed in both CHR and ZZ. Most of the
      differentially expressed lncRNAs were hypothesized to be associated with
      chlorantraniliprole resistance in P. xylostella. The targets of lncRNAs via cis-
      (<10 kb upstream and downstream) or trans- (Pearson's correlation, r > 0.9 or < 
      0.9, P < 0.05) regulatory effects were also identified; many of the differently
      expressed lncRNAs were correlated with various important protein-coding genes
      involved in insecticide resistance, such as the ryanodine receptor, uridine
      diphosphate glucuronosyltransferase (UGTs), cytochrome P450, esterase and the ATP
      binding cassette transporter. CONCLUSIONS: Our results represent the first global
      identification of lncRNAs associated with chlorantraniliprole resistance in P.
      xylostella. These results will facilitate future studies of the regulatory
      mechanisms of lncRNAs in chlorantraniliprole and other insecticide resistance and
      in other biological processes in P. xylostella.

PMID- 28506254
TI  - Reemergence of yellow fever in Ethiopia after 50 years, 2013: epidemiological and
      entomological investigations.
AB  - BACKGROUND: Yellow Fever (YF) is a viral hemorrhagic disease transmitted by aedes
      mosquito species. Approximately, 200,000 cases and 30,000 deaths occur worldwide
      every year. In Ethiopia, the last outbreak was reported in 1966 with 2200 cases
      and 450 deaths. A number of cases with deaths from unknown febrile illness
      reported from South Ari district starting from November 2012. This investigation
      was conducted to identify the causative agent, source of the outbreak and
      recommend appropriate interventions. METHODS: Medical records were reviewed and
      Patients and clinicians involved in managing the case were interviewed.
      Descriptive data analysis was done by time, person and place. Serum samples were
      collected for serological analysis it was done using Enzyme-linked Immunosorbent
      Assay for initial screening and confirmatory tests were done using Plaque
      Reduction and Neutralization Test. Breteau and container indices were used for
      the entomological investigation to determine the risk of epidemic. RESULTS: A
      total of 141 Suspected YF cases with 43 deaths (CFR = 30.5%) were reported from
      November 2012 to October 2013 from South Omo Zone. All age groups were affected
      (mean 27.5, Range 1-75 Years). Of the total cases, 85.1% cases had jaundice and
      56.7% cases had fever. Seven of the 21 samples were IgM positive for YF virus.
      Aedes bromeliae and Aedes aegypti were identified as responsible vectors of YF in
      affected area. The Breteau indices of Arkisha and Aykamer Kebeles were 44.4% and
      33.3%, whereas the container indices were 12.9% and 22.2%, respectively.
      CONCLUSION: The investigation revealed that YF outbreak was reemerged after 50
      years in Ethiopia. Vaccination should be given for the affected and neighboring
      districts and Case based surveillance should be initiated to detect every case.

PMID- 28506255
TI  - Retrospective study of nonmucinous appendiceal adenocarcinomas: role of systemic
      chemotherapy and cytoreductive surgery.
AB  - BACKGROUND: Mucinous appendiceal adenocarcinomas (AAs) are the most common
      histological subset of AAs. Nonmucinous AAs have been infrequently studied. We
      performed a single-center retrospective study to investigate this histological
      subtype. METHODS: We reviewed 172 patient records with nonmucinous AAs treated at
      MD Anderson Cancer Center from Jan, 1990 to Jun, 2015 and recorded patient
      demographics, tumor characteristics, treatment, and outcomes. Response rate (RR)
      was assessed semi-quantitatively (response/no response) according to the treating
      physician's findings. Survival outcomes were calculated using the Kaplan-Meier
      product-limit method and compared using the log-rank test. RESULTS: Median age at
      diagnosis was 52.9 years. Most patients presented with advanced-stage disease:
      stage I-II (35%), stage III (15%), and stage IV (50%). Moderate and poorly
      differentiated histology was seen in 56% and 44% tumors, respectively. Median
      overall survival (OS) of all patients was stage-dependent and was 88.5, 39.2, and
      28.3 months for stages I-II, stage III, and stage IV disease, respectively (p <
      0.0001). In patients with metastatic disease, only 10% had extraperitoneal
      disease without peritoneal involvement. Cytoreductive surgery (CRS) was attempted
      in 31/69 (45%) patients with disease confined to the peritoneum. Complete CRS was
      achieved in 18. Median OS for patients receiving complete CRS was 48.6 months.
      Systemic chemotherapy was administered to 109 (86%) patients with metastatic
      disease; a large majority of patients received either an oxaliplatin-based (55%)
      or irinotecan-based (27%) regimen. Chemotherapy resulted in a semi-quantitative
      RR of 54% and median time to progression (TTP) of 9.4 months (95% CI, 8.03
      11.50). Patients who received combination chemotherapy (either oxaliplatin or
      irinotecan-based) showed significantly longer median OS (p = 0.003), compared to
      those receiving fluoropyrimidine monotherapy. CONCLUSIONS: This is one of the
      first studies to report specifically on nonmucinous AAs. Nonmucinous AAs
      presented with moderate or poorly differentiated histology with a predilection
      for peritoneal metastasis. Systemic chemotherapy is active in this AA subtype.
      Though CRS was infrequently used, complete CRS appears beneficial and warrants
      further investigation.

PMID- 28506256
TI  - AAV vector distribution in the mouse respiratory tract following four different
      methods of administration.
AB  - BACKGROUND: Targeted delivery of gene therapy vectors to the mouse respiratory
      tract is often performed via intranasal or intratracheal administration; however,
      there can be a great deal of variability between these methods, which could
      potentially influence experimental results. Improving the accuracy and precision
      of lung delivery will not only reduce the number of animals required to detect
      statistically significant differences, but may reduce the variability of studies
      from different laboratories. RESULTS: Here we evaluated three different methods
      of adeno-associated virus (AAV) vector administration to the respiratory tract in
      mice (intranasal, intubation, and intratracheal injection) and discuss the
      advantages, challenges, and shortcomings of each. We also present a modified
      intranasal delivery technique that is superior to passive administration of
      vector into the nares of anesthetized supine animals. Transgene expression was
      consistently visible in the nasal cavity, trachea, and proximal to middle aspect
      of all lung lobes for all four methods, whereas transgene expression was
      consistently observed in the most distal aspect of lung lobes only with the
      intubation and intratracheal injection techniques. AAV vector genome copy numbers
      in the lung were approximately four-fold lower in mice that received vector via
      intranasal administration in comparison to the other three methods of vector
      delivery. The modified intranasal, intubation and intratracheal injection methods
      of vector administration did not yield statistical differences in AAV vector
      genome copy numbers in the lung. With regard to reproducibility of vector
      distribution within and between animals, the modified-intranasal technique was
      superior. CONCLUSION: Our results show that mode of AAV vector administration to
      the murine respiratory tract should be selected based on desired target site and
      skill of the researcher, and that appropriate technique selection may greatly
      influence experimental outcomes.

PMID- 28506258
TI  - Health care waste management in community-based care: experiences of community
      health workers in low resource communities in South Africa.
AB  - BACKGROUND: In South Africa, community health workers (CHWs) working in community
      based care (CBC) programmes provide care to patients most of whom are living with
      HIV/AIDS and tuberculosis (TB). Although studies have shown that the caregiving
      activities provided by the CHWs generate health care waste (HCW), there is
      limited information about the experiences of CHWs on health care waste management
      (HCWM) in CBC. This study explored HCWM in CBC in Durban, South Africa from the
      perspectives CHWs. METHODS: We used three ethnographic approaches to collect
      data: focus group discussions, participant observations and informal discussions.
      Data was collected from 85 CHWs working in 29 communities in the Durban
      metropolis, South Africa. Data collection took place from July 2013 to August
      2014. RESULTS: CHWs provided nursing care activities to patients many of whom
      were incontinent or bedridden. Some the patients were living with HIV/AIDS/TB,
      stroke, diabetes, asthma, arthritis and high blood pressure. These caregiving
      activities generate sharps and infectious waste but CHWs and family members did
      not segregate HCW according to the risk posed as stipulated by the HCWM policy.
      In addition, HCW was left with domestic waste. Major barriers to proper HCWM
      identified by CHWs include, lack of assistance from family members in assisting
      patients to use the toilet or change diapers and removing HCW from homes,
      irregular waste collection by waste collectors, inadequate water for practicing
      hygiene and sanitation, long distance between the house and the toilets and poor
      conditions of communal toilets and pit latrines. As a result of these barriers,
      HCW was illegally dumped along roads or in the bush, burnt openly and buried
      within the yards. Liquid HCW such as vomit, urine and sputum were disposed in
      open spaces near the homes. CONCLUSION: Current policies on primary health care
      (PHC) and HCWM in South Africa have not paid attention to HCWM. Findings suggest
      the need for primary health care reform to develop the competencies of CHWs in
      HCWM. In addition, PHC and HCWM policies should address the infrastructure
      deficit in low resource communities. In order for low-and-middle-income-countries
      (LMICs) to develop effective community health worker programmes, there is a need
      for synergies in PHC and HCWM policies.

PMID- 28506257
TI  - An overview of systematic reviews of complementary and alternative therapies for
      fibromyalgia using both AMSTAR and ROBIS as quality assessment tools.
AB  - BACKGROUND: Fibromyalgia (FM) is a chronic, debilitating pain disorder.
      Dissatisfaction with conventional medicine can lead people with FM to turn to
      complementary and alternative medicine (CAM). Two previous overviews of
      systematic reviews of CAM for FM have been published, but they did not assessed
      for risk of bias in the review process. METHODS: Five databases Medline, Embase,
      AMED (via OVID), Web of Science and Central were searched from their inception to
      December 2015. Reference lists were hand-searched. We had two aims: the first was
      to provide an up-to-date and rigorously conducted synthesis of systematic reviews
      of CAM literature on FM; the second was to evaluate the quality of the available
      systematic review evidence using two different tools: AMSTAR (Shea et al. BMC Med
      Res Methodol 15; 7:10, 2007) and a more recently developed tool ROBIS (Whiting et
      al. J Clin Epidemiol 69:225-34, 2016) specifically designed to assess risk of
      bias in systematic reviews. Any review that assessed one of eight CAM therapies
      for participants diagnosed with FM was considered. The individual studies had to
      be randomised controlled trials where the intervention was compared to placebo,
      treatment as usual or waitlist controls to be included. The primary outcome
      measure was pain, and the secondary outcome measure was adverse events. RESULTS:
      We identified 15 reviews that met inclusion criteria. There was low-quality
      evidence that acupuncture improves pain compared to no treatment or standard
      treatment, but good evidence that it is no better than sham acupuncture. The
      evidence for homoeopathy, spinal manipulation and herbal medicine was limited.
      CONCLUSIONS: Overall, five reviews scored 6 or above using the AMSTAR scale and
      the inter-rater agreement was good (83.6%), whereas seven reviews achieved a low
      risk of bias rating using ROBIS and the inter-rater agreement was fair (60.0%).
      No firm conclusions were drawn for efficacy of either spinal manipulation or
      homoeopathy for FM. There is limited evidence for topical Capsicum, but further
      research is required. There is some evidence to support the effectiveness of
      acupuncture for FM, but further high-quality trials are needed to investigate its
      benefits, harms and mechanisms of action, compared with no or standard treatment.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035846 .

PMID- 28506259
TI  - Detection of antibacterial activities of Miswak, Kalonji and Aloe vera against
      oral pathogens & anti-proliferative activity against cancer cell line.
AB  - BACKGROUND: Emerging drug resistance and hindrance of treatment is provoking
      scientists to search new, less expensive medicinally active compounds. Dental
      diseases caused by oral pathogens are very frequent chronic infections around the
      world. The medical potentials of a lot of Pakistani local herbs and herbal
      combinations is relatively unknown, hence attempted to explore. A study was
      designed to investigate potential role of local medicinal herbs for example
      Miswak, Kalonji & Aloe vera as antimicrobial, antioxidant and anti-proliferative
      agents against oral pathogens and cancer cell line. METHODS: Medicinal extracts
      were prepared in solvents of different polarities. Their antimicrobial activity
      was determined alone and in combination against oral pathogens. Antioxidant
      activity was evaluated through Catalase and Superoxide dismutase assay and anti
      proliferative activity was evaluated through 3-(4, 5-Dimethylthiazol-2-Yl)-2,5
      Diphenyltetrazolium Bromide) assay. RESULTS: Plant extracts alone and in
      combinations were found significantly effective as antimicrobial agent against
      standard ATCC strains of C. albicans and S. aureus (P ?0.001). Especially Miwak
      extract was found highly significant against fungus. Extracts of Kalonji were
      found significant in inhibiting growth of HeLa cell lines. Miswak and Kalonji
      showed significant levels of antioxidant activity. CONCLUSION: Medicinal herbs
      Miswak and Kalonji have potential to be used for therapeutic purposes. Results
      suggested that herbal medicinal composition can be prepared using these extracts
      after applying scientific standardization methods.

PMID- 28506261
TI  - A possible role of low regulatory T cells in anti-acetylcholine receptor antibody
      positive myasthenia gravis after bone marrow transplantation.
AB  - BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months
      following allogenic hematopoietic stem cell transplantation (HSCT) and is
      clinically analogous to autoimmune disorder. Polymyositis is a common
      neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely
      rare. Hence, its pathophysiology and treatment have not been elucidated. CASE
      PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with
      ptosis, dropped head, and dyspnea on exertion, which had worsened over the
      previous several months. He showed progressive decrement of compound muscle
      action potential in the deltoid muscle evoked by 3-Hz repetitive nerve
      stimulation, a positive edrophonium test, and elevated levels of serum anti
      acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG.
      No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of
      peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes).
      Administration of prednisolone and tacrolimus was insufficient to alleviate his
      symptoms; however, the use of rituximab successfully improved his condition.
      CONCLUSIONS: Myasthenic symptoms appeared in the process of tapering prednisolone
      for the treatment of chronic GVHD, supporting the diagnosis of MG associated with
      chronic GVHD. The present case proposes a possibility that reduction of Tregs
      might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy
      with rituximab is beneficial for treatment of refractory MG and GVHD.

PMID- 28506260
TI  - Atypical retinal pigment epithelial defects with retained photoreceptor layers: a
      so far disregarded finding in age related macular degeneration.
AB  - BACKGROUND: To report patients with age-related macular degeneration and atypical
      central retinal pigment epithelium (RPE) defects not attributable to geographic
      atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. METHODS:
      Multimodal imaging case-series evaluating the course of atypical RPE- defects in
      patients with AMD using Color fundus images, Optical coherence tomography (OCT),
      OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA).
      RESULTS: Ten patients were identified. Three patients had a prior RPE-rip and
      were excluded. Seven patients with a mean follow-up period of 47 +/- 38 months
      after the occurrence of the RPE-defect were included (age range 71-87 years).
      Mean distance Best corrected visual acuity (BCVA) at initial presentation was
      0.36 +/- 0.29logMAR and at last follow-up visit 0.51 +/- 0.43logMAR. Patients
      presented with clinically apparent GA on funduscopy and FAF, but preserved
      photoreceptor layers on optical coherence tomography (OCT). On FA there was early
      hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid
      material right above the Bruch's membrane with concomitant decrease of
      hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect
      was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid
      pigment epithelium detachment (PED) preceding the lesion. CONCLUSIONS: Beside GA
      and characteristic RPE-tears, another atypical form of RPE-defect with overlying
      preserved photoreceptor layers are found in AMD. This so far disregarded subgroup
      of patients present with reasonable visual function and long-term survival of
      photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid
      material and persistent subretinal fluid (SRF), but also a RPE-independent visual
      cycle for cone photopigment within the neurosensory retina may contribute to
      their favorable course.

PMID- 28506262
TI  - Identification and quantification of virulence factors of enterotoxigenic
      Escherichia coli by high-resolution melting curve quantitative PCR.
AB  - BACKGROUND: Diagnosis of enterotoxigenic E. coli (ETEC) associated diarrhea is
      complicated by the diversity of E.coli virulence factors. This study developed a
      multiplex quantitative PCR assay based on high-resolution melting curves analysis
      (HRM-qPCR) to identify and quantify genes encoding five ETEC fimbriae related to
      diarrhea in swine, i.e. K99, F41, F18, F6 and K88. METHODS: Five fimbriae
      expressed by ETEC were amplified in multiple HRM-qPCR reactions to allow
      simultaneous identification and quantification of five target genes. The assay
      was calibrated to allow quantification of the most abundant target gene, and
      validated by analysis of 30 samples obtained from piglets with diarrhea and
      healthy controls, and comparison to standard qPCR detection. RESULTS: The five
      amplicons with melting temperatures (Tm) ranging from 74.7 +/- 0.06 to 80.5 +/-
      0.15  degrees C were well-separated by HRM-qPCR. The area of amplicons under the
      melting peak correlated linearly to the proportion of the template in the
      calibration mixture if the proportion exceeded 4.8% (K88) or <1% (all other
      amplicons). The suitability of the method was evaluated using 30 samples from
      weaned pigs aged 6-7 weeks; 14 of these animals suffered from diarrhea in
      consequence of poor sanitary conditions. Genes encoding fimbriae and enterotoxins
      were quantified by HRM-qPCR and/or qPCR. The multiplex HRM-qPCR allowed accurate
      analysis when the total gene copy number of targets was more than 1 * 105 / g wet
      feces and the HRM curves were able to simultaneously distinguish fimbriae genes
      in the fecal samples. The relative quantification of the most abundant F18 based
      on melting peak area was highly correlated (P < 0.001; r2 = 0.956) with that of
      individual qPCR result but the correlation for less abundant fimbriae was much
      lower. CONCLUSIONS: The multiplex HRM assay identifies ETEC virulence factors
      specifically and efficiently. It correctly indicated the predominant fimbriae
      type and additionally provides information of presence/ absence of other fimbriae
      types and it could find broad applications for pathogen diagnosis.

PMID- 28506263
TI  - Mindfulness-based stress reduction in Parkinson's disease: a systematic review.
AB  - BACKGROUND: Mindfulness based stress reduction (MBSR) is increasingly being used
      to improve outcomes such as stress and depression in a range of long-term
      conditions (LTCs). While systematic reviews on MBSR have taken place for a number
      of conditions there remains limited information on its impact on individuals with
      Parkinson's disease (PD). METHODS: Medline, Central, Embase, Amed, CINAHAL were
      searched in March 2016. These databases were searched using a combination of MeSH
      subject headings where available and keywords in the title and abstracts. We also
      searched the reference lists of related reviews. Study quality was assessed based
      on questions from the Cochrane Collaboration risk of bias tool. RESULTS: Two
      interventions and three papers with a total of 66 participants were included. The
      interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study
      reported significantly increased grey matter density (GMD) in the brains of the
      MBSR group compared to the usual care group. Significant improvements were
      reported in one study for a number of outcomes including PD outcomes, depression,
      mindfulness, and quality of life indicators. Only one intervention was of
      reasonable quality and both interventions failed to control for potential
      confounders in the analysis. Adverse events and reasons for drop-outs were not
      reported. There was also no reporting on the costs/benefits of the intervention
      or how they affected health service utilisation. CONCLUSION: This systematic
      review found limited and inconclusive evidence of the effectiveness of MBSR for
      PD patients. Both of the included interventions claimed positive effects for PD
      patients but significant outcomes were often contradicted by other results.
      Further trials with larger sample sizes, control groups and longer follow-ups are
      needed before the evidence for MBSR in PD can be conclusively judged.

PMID- 28506264
TI  - An association between pulmonary Mycobacterium avium-intracellulare complex
      infections and biomarkers of Th2-type inflammation.
AB  - BACKGROUND: The rising incidence of pulmonary Mycobacterium avium-intracellulare
      complex (MAI) infection is unexplained but parallels the growing world-wide
      epidemic of allergic disease. We hypothesized an association between pulmonary
      MAI infection and Th2-type immune responses as seen in allergy. METHODS:
      Biomarkers of patient Th2-type immune responses (peripheral blood eosinophil
      counts and serum IgE levels) were compared between patients with positive
      pulmonary samples for tuberculosis and non-tuberculous mycobacterial (NTM)
      infection. A further comparison of clinical characteristics, including
      respiratory co-morbidities, and biomarkers, was conducted between patients
      culturing MAI NTM and those culturing NTM other than MAI. RESULTS: Patients
      culturing NTM from pulmonary samples had significantly higher peripheral blood
      eosinophil levels than those culturing Mycobacterium tuberculosis. Furthermore,
      patients culturing MAI compared to those culturing NTM other than MAI had higher
      eosinophil counts (mean 0.29x109/L vs 0.15x109/L, p = 0.010) and IgE levels
      (geometric mean 138kU/L vs 47kU/L, p = 0.021). However there was no significant
      difference in the frequency of asthma between the two NTM groups. CONCLUSIONS:
      There is an association between biomarkers of Th2-type immune responses and
      pulmonary MAI. Prospective and translational research could identify the
      direction of causation; and so determine whether our finding may be utilized
      within future management strategies for MAI.

PMID- 28506265
TI  - Determinants of poor utilization of antenatal care services among recently
      delivered women in Rwanda; a population based study.
AB  - BACKGROUND: In Rwanda, a majority of pregnant women visit antenatal care (ANC)
      services, however not to the extent that is recommended. Association between
      socio-demographic or psychosocial factors and poor utilization of antenatal care
      services (<=2 visits during the course of pregnancy irrespective of the timing)
      among recently pregnant women in Rwanda were investigated. METHODS: This
      population-based, cross sectional study included 921 women who gave birth within
      the past 13 months. Data was obtained using an interviewer-administered
      questionnaire. For the analyses, bi-and multivariable logistic regression was
      used and odds ratios were presented with their 95% confidence intervals. RESULTS:
      About 54% of pregnant women did not make the recommended four visits to ANC
      during pregnancy. The risk of poor utilization of ANC services was higher among
      women aged 31 years or older (AOR, 1.78; 95% CI: 1.14, 2.78), among single women
      (AOR, 2.99; 95% CI: 1.83, 4.75) and women with poor social support (AOR, 1.71;
      95% CI: 1.09, 2.67). No significant associations were found for school attendance
      or household assets (proxy for socio-economic status) with poor utilization of
      ANC services. CONCLUSION: Older age, being single, divorced or widowed and poor
      social support were associated with poor utilization of ANC services. General
      awareness in communities should be raised on the importance of the number and
      timing of ANC visits. ANC clinics should further be easier to access, transport
      should be available, costs minimized and opening hours may be extended to
      facilitate visits for pregnant women.

PMID- 28506267
TI  - A qualitative study on acceptable levels of risk for pregnant women in clinical
      research.
AB  - BACKGROUND: There is ambiguity with regard to what counts as an acceptable level
      of risk in clinical research in pregnant women and there is no input from
      stakeholders relative to such research risks. The aim of our paper was to explore
      what stakeholders who are actively involved in the conduct of clinical research
      in pregnant women deem an acceptable level of risk for pregnant women in clinical
      research. Accordingly, we used the APOSTEL VI study, a low-risk obstetrical
      randomised controlled trial, as a case-study. METHODS: We conducted a prospective
      qualitative study using 35 in-depth semi-structured interviews and one focus
      group. We interviewed healthcare professionals, Research Ethics Committee members
      (RECs) and regulators who are actively involved in the conduct of clinical
      research in pregnant women, in addition to pregnant women recruited for the
      APOSTEL VI case-study in the Netherlands. RESULTS: Three themes characterise the
      way stakeholders view risks in clinical research in pregnant women in general.
      Additionally, one theme characterises the way healthcare professionals and
      pregnant women view risks with respect to the case-study specifically. First,
      ideas on what constitutes an acceptable level of risk in general ranged from a
      preference for zero risk for the foetus up to minimal risk. Second, the
      desirability of clinical research in pregnant women in general was questioned
      altogether. Third, stakeholders proposed to establish an upper limit of risk in
      potentially beneficial clinical research in pregnant women in order to protect
      the foetus and the pregnant woman from harm. Fourth and finally, the case-study
      illustrates that healthcare professionals' individual perception of risk may
      influence recruitment. CONCLUSIONS: Healthcare professionals, RECs, regulators
      and pregnant women are all risk adverse in practice, possibly explaining the
      continuing underrepresentation of pregnant women in clinical research.
      Determining the acceptable levels of risk on a universal level alone is
      insufficient, because the individual perception of risk also influences behaviour
      towards pregnant women in clinical research. Therefore, bioethicists and
      researchers might be interested in changing the perception of risk, which could
      be achieved by education and awareness about the actual benefits and harms of
      inclusion and exclusion of pregnant women.

PMID- 28506266
TI  - Impact of preterm birth on infant mortality for newborns with congenital heart
      defects: The EPICARD population-based cohort study.
AB  - BACKGROUND: Congenital heart defects (CHD) and preterm birth (PTB) are major
      causes of infant mortality. However, limited data exist on risk of mortality
      associated with PTB for newborns with CHD. Our objective was to assess impact of
      PTB on risk of infant mortality for newborns with CHD, while taking into account
      the role of associated anomalies and other potentially confounding factors.
      METHODS: We used data on 2172 live births from a prospective population-based
      cohort study of CHD (the EPICARD Study) and compared neonatal, post-neonatal and
      overall infant mortality for infants born at <32, 32-34 and 35-36 weeks vs. those
      born at term (37-41 weeks). RESULTS: Preterm newborns had a 3.8-fold higher risk
      of infant death (17.9%) than term newborns (4.7%), RR 3.8, 95%CI 2.7-5.2; the
      risk associated with PTB was more than four-fold higher for neonatal (RR 4.3, 95%
      CI 2.9-6.6) and three-fold higher for post-neonatal deaths (RR 3.0, 95% CI 1.7
      5.2). Survival analysis showed that newborns <35 weeks had a higher risk of
      mortality, which decreased but persisted after exclusion of associated anomalies
      and adjustment for potential confounders. CONCLUSIONS: Preterm birth is
      associated with an approximately four-fold higher risk of infant mortality for
      newborns with CHD. This excess risk appears to be mostly limited to newborns <35
      weeks of gestation and is disproportionately due to early deaths.

PMID- 28506268
TI  - Ethnic differences in folic acid supplement use in a population-based cohort of
      pregnant women in Norway.
AB  - BACKGROUND: Peri-conceptional use of folic acid supplements is recommended to
      prevent neural tube defects. Correct supplement use seems to be less common among
      ethnic minorities. We examined ethnic differences in folic acid supplement use
      before and during pregnancy and possible effect modification by education or
      planning of pregnancy. METHODS: The participants were 811 healthy pregnant women
      from a population-based cohort study in Oslo, Norway in 2008-2010. Ethnicity was
      categorized to five groups (European, Middle Eastern, South Asian, East Asian,
      African). Data on folic acid supplement use were obtained from hospital records
      and remaining data by a questionnaire. Logistic regression analyses were adjusted
      for age, parity, planning of pregnancy, education and Norwegian language skills.
      RESULTS: Before pregnancy, 30.1% of European women and 7.1 to 13.6% of women in
      the other ethnic groups used folic acid supplements (p < 0.001). The adjusted
      odds ratio (OR) for supplement use was 0.55 (95% confidence interval 0.31; 0.96)
      for South Asian and 0.42 (95% confidence interval 0.19; 0.94) for Middle Eastern
      women compared with European women. During pregnancy, supplement use was most
      common in European women (65.7%) and least common in Middle Eastern (29.4%) and
      African women (29.0%) (p < 0.001). Compared with European women, all other ethnic
      groups had lower adjusted odds (OR 0.30 to 0.50, p < 0.05 for all) for supplement
      use among women with high school or less education, but not among more educated
      women. Planning of pregnancy did not modify the association between ethnicity and
      supplement use. CONCLUSIONS: Few women used folic acid supplements before
      pregnancy. Educational level modified the association between ethnicity and
      supplement use during pregnancy. Public health campaigns should focus on
      increasing awareness especially in ethnic minority groups with low educational
      level.

PMID- 28506270
TI  - Predictors of preferred location of care in middle-aged individuals of a
      municipality in Japan: a cross-sectional survey.
AB  - BACKGROUND: Japan has the highest rate of aging. To contain Long-Term Care (LTC)
      Insurance costs, the Japanese government is attempting to increase the proportion
      of individuals receiving home care services. However, demand for institutional
      care is increasing. These circumstances will decrease the sustainability of the
      LTC Insurance System. The objective of the present study was to identify
      predictors of the location of preference for LTC (home or a facility) in middle
      aged individuals in a municipality. METHODS: This was a cross-sectional study of
      middle-aged individuals (n = 906) in Tsukuba, Japan. Data primarily included
      individual or social factors (sex, age, household size, experience with caring
      for family, information sources about social services or municipality policy),
      factors about care prevention (self-reported health, efforts to promote health,
      motivation in life), and the preferred location of care. These variables were
      analysed with multiple logistic regression, using preferred location of care as
      the dependent variable. RESULTS: A total of 693 respondents were analysed. Of
      these, 440 (63.5%) preferred home and 253 (36.5%) preferred a facility. The
      results of logistic regression analysis showed that a preference for facility was
      significantly associated with female sex, younger age, experience with caring for
      family, fewer information sources about social services or municipality policies,
      selecting 'go to culture lessons/study to satisfy interests', and not selecting
      'spending time happily with family' under motivation in life. CONCLUSIONS: To
      support the selection of receiving home care services, municipalities must
      consider improving policies that reduce the burdens of present middle-aged
      caregivers, and promote the provision of care service information from multiple
      sources.

PMID- 28506269
TI  - The emerging roles and therapeutic potential of exosomes in epithelial ovarian
      cancer.
AB  - Ovarian cancer (OC) is one of the three types of malignant tumors in the female
      reproductive system, and epithelial ovarian cancer (EOC) is its most typical
      form. Due to the asymptomatic nature of the early stages and resistance to
      chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current
      treatments for OC are very limited, and the 5-years survival rate is
      approximately 30%. Exosomes, which are microvesicles ranging from approximately
      30-100 nm in size that are secreted by living cells, can be produced from
      different cell types and detected in various body fluids. Cancer cells can
      secrete more exosomes than healthy cells, and more importantly, the content of
      cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells
      are considered to be involved in tumor progression and metastasis. As such,
      exosomes are expected to be potential tools for tumor diagnosis and treatment. In
      this review, we briefly present the emerging roles of exosomes in OC and
      summarize related articles about their roles as diagnostic or prognostic
      biomarkers and in the treatment and drug resistance of OC.

PMID- 28506271
TI  - Agrobiodiversity and in situ conservation in ethnic minority communities of
      Xishuangbanna in Yunnan Province, Southwest China.
AB  - BACKGROUND: Xishuangbanna of Yunnan Province, southwest of China belongs to a
      global biodiversity and cultural hotspot. Agrobiodiversity plays an essential
      role in local livelihoods and traditional culture in the region. However,
      preliminary studies suggest that diversity of crop plants and livestock species
      is declining. We hypothesized that agrobiodiversity and traditional means of
      preserving agrobiodiversity are threatened because of changes in government
      policy in favor of commercial plantations, land use change and changes in
      traditional agricultural practices. We investigated whether or not
      agrobiodiversity was declining, the specific causes, and signs of active
      biodiversity conservation practices in ethnic minority communities of
      Xishuangbanna which could form the basis for extensive in situ conservation
      programmes. METHODS: A series of field studies to document trends in
      agrobiodiversity were conducted in different ethnic minority communities in
      Menghai County, Mengla County and Jinghong City of Xishuangbanna of Yunnan
      Province, southwest of China between July 2015 and February 2016. Data was
      obtained through the use of semi-structured questionnaires, field observation and
      participatory rural appraisal (PRA) tools. A total of 360 ethnic households
      provided information on current status, functions, characteristics, changes, and
      threatened factors of farming crop and livestock resources. Some measures for in
      situ conservation of agricultural biological resources were also researched using
      PRA methods. RESULTS: Two hundred twenty-six crop varieties belonging to 31
      families, 71 genera and 101 species were identified in Xishuangbanna, which
      included 83 vegetable crops, 77 food crops, 24 spice crops, 22 fruit crops, 13
      cash crops, 6 oil crops, and 1 cloth crop, respectively. There were 15 livestock
      varieties, belonging to 6 major species: cattle, pigs, goats, chickens, ducks,
      and geese. Different crop and livestock resources had their own characteristics,
      functions and threatened factors. Since 2002, agroecosystem, crop diversity and
      livestock diversity have declined greatly over the Xishuangbanna region as a
      whole under implementation of the Sloping Land Conversion Program (SLCP). Swidden
      agriculture was completely eliminated under this program and gradually replaced
      by large land areas devoted to rubber, tea and banana plantations. Villager
      numbers engaging in farming production and population of crops and livestock were
      greatly decreased, particularly in terms of production of local traditional
      varieties. However, some in situ conservation measures such as seeds
      preservation, planting of traditional crops and raising livestock have played an
      important role in local agrobiodiversity conservation. CONCLUSION: Abundant
      agricultural resources and agrobiodiversity are critical to the local livelihood
      and maintenance of traditional culture in Xishuangbanna. However,
      agrobiodiversity and related traditional culture have been greatly impacted by
      implementation of the SLCP since 2002. Therefore, in future conservation of
      agrobiodiversity, incorporating some sustainable protection measures based in
      local communities such as convening seed exchange fairs, conserving traditional
      varieties in permanent plots, making a visual documentary of indigenous
      cultivation, and providing traditional agricultural products to tourists should
      be carefully considered and adopted.

PMID- 28506272
TI  - Prevalence and clonal relationship of ESBL-producing Salmonella strains from
      humans and poultry in northeastern Algeria.
AB  - BACKGROUND: The aims of this study were to investigate Salmonella contamination
      in broiler chicken farms and slaughterhouses, to assess the antibiotic resistance
      profile in avian and human Salmonella isolates, and to evaluate the relationship
      between avian and human Extended Spectrum beta-Lactamase (ESBL)-producing
      isolates. Salmonella was screened in different sample matrices collected at
      thirty-two chicken farms and five slaughterhouses. The human isolates were
      recovered from clinical specimens at the University Teaching Hospital of
      Constantine (UTH). All suspected colonies were confirmed by MALDI-TOF (Matrix
      Assisted Laser Desorption Ionization Time OF light) and serotyped. Susceptibility
      testing against 13 antibiotics including, amoxicillin/clavulanic acid,
      ticarcillin, cefoxitin, cefotaxime, aztreonam, imipenem, ertapenem, gentamicin,
      amikacin, ciprofloxacin, colistin, trimethoprim/sulfamethoxazole and fosfomycin,
      was performed using the disk diffusion method on Mueller-Hinton agar. ESBL
      production was screened by the double-disk synergy test and confirmed by
      molecular characterization using PCR (polymerase chain reaction) amplification
      and sequencing of ESBL encoding genes. Clonality of the avian and human strains
      was performed using the Multi Locus Sequencing Typing method (MLST). RESULTS:
      Forty-five isolated avian Salmonella strains and 37 human collected ones were
      studied. Five S. enterica serotypes were found in avian isolates (mainly
      Kentucky) and 9 from human ones (essentially Infantis). 51.11% and 26.6% of the
      avian isolates were resistant to ciprofloxacin and cefotaxime, respectively,
      whereas human isolates were less resistant to these antibiotics (13.5% to
      ciprofloxacin and 16.2% to cefotaxime). Eighteen (12 avian and 6 human) strains
      were found to produce ESBLs, which were identified as bla CTX-M-1 (n = 12), bla
      CTX-M-15 (n = 5) and bla TEM group (n = 8). Interestingly, seven of the ESBL
      producing strains (5 avian and 2 human) were of the same ST (ST15) and clustered
      together, suggesting a common origin. CONCLUSION: The results of the combined
      phenotypic and genotypic analysis found in this study suggest a close
      relationship between human and avian strains and support the hypothesis that
      poultry production may play a role in the spread of multidrug-resistant
      Salmonella in the human community within the study region.

PMID- 28506273
TI  - Inertial measurement systems for segments and joints kinematics assessment:
      towards an understanding of the variations in sensors accuracy.
AB  - BACKGROUND: Joints kinematics assessment based on inertial measurement systems,
      which include attitude and heading reference system (AHRS), are quickly gaining
      in popularity for research and clinical applications. The variety of the tasks
      and contexts they are used in require a deep understanding of the AHRS accuracy
      for optimal data interpretation. However, published accuracy studies on AHRS are
      mostly limited to a single task measured on a limited number of segments and
      participants. This study assessed AHRS sensors kinematics accuracy at multiple
      segments and joints through a variety of tasks not only to characterize the
      system's accuracy in these specific conditions, but also to extrapolate the
      accuracy results to a broader range of conditions using the characteristics of
      the movements (i.e. velocity and type of motion). Twenty asymptomatic adults
      ([Formula: see text] = 49.9) performed multiple 5 m timed up and go.
      Participants' head, upper trunk, pelvis, thigh, shank and foot were
      simultaneously tracked using AHRS and an optical motion capture system (gold
      standard). Each trial was segmented into basic tasks (sit-to-stand, walk, turn).
      RESULTS: At segment level, results revealed a mean root-mean-squared-difference
      [Formula: see text] varying between 1.1 degrees  and 5.5 degrees  according to
      the segment tracked and the task performed, with a good to excellent agreement
      between the systems. Relative sensor kinematics accuracy (i.e. joint) varied
      between 1.6 degrees  and 13.6 degrees  over the same tasks. On a global scheme,
      analysis of the effect of velocity on sensor kinematics accuracy showed that AHRS
      are better adapted to motions performed between 50 degrees /s and 75 degrees /s
      (roughly thigh and shank while walking). CONCLUSION: Results confirmed that
      pairing of modules to obtain joint kinematics affects the accuracy compared to
      segment kinematics. Overall, AHRS are a suitable solution for clinical evaluation
      of biomechanics under the multi-segment tasks performed although the variation in
      accuracy should be taken into consideration when judging the clinical
      meaningfulness of the observed changes.

PMID- 28506274
TI  - Contextual and psychosocial factors predicting Ebola prevention behaviours using
      the RANAS approach to behaviour change in Guinea-Bissau.
AB  - BACKGROUND: The outbreak of the Ebola virus disease (EVD) in West Africa in
      December 2013 was the largest Ebola outbreak in history. This study aimed to
      measure the underlying contextual and psychosocial factors of intentions to
      perform Ebola prevention behaviours (not touching people who might be suffering
      from Ebola, reporting suspected cases to the National Ebola Hotline, NEH) in
      Guinea-Bissau. Geographical location, cross-border market activities, poor water,
      sanitation and hygiene (WASH) conditions, and burial practices in some
      communities pose a serious risk in terms of potential EVD outbreak and seriously
      hamper its prevention in Guinea-Bissau. METHODS: In July and August 2015,
      quantitative data from 1369 respondents were gathered by structured face-to-face
      interviews. The questionnaire was based on the psychosocial factors of the RANAS
      (risks, attitudes, norms, abilities, and self-regulation) model. Data were
      analyzed by multiple linear regression analyses. RESULTS: The most important
      predictors for the intention to call the NEH were believing that calling the
      Hotline would help the infected person, perceiving that important members from
      the household approve of calling the Hotline, thinking that calling the Hotline
      is something they should do, and believing that it is important to call the
      Hotline to report a suspected case. For the intention not to touch someone who
      might be suffering from Ebola, the most important predictors were health
      knowledge, the perception of risk with regard to touching a person who might be
      suffering from Ebola, and the belief that they were able not to touch a possibly
      infected person. Age in years was the only significant contextual predictor for
      one of the two behavioural intentions, the intention to call the Hotline. It
      seems that younger people are more likely to use a service like the NEH than
      older people. CONCLUSIONS: Strengths and gaps were identified in the study
      population in relation to the intention to perform prevention behaviours. These
      call for innovative ways of aligning existing hygiene programs with relevant
      psychosocial factors. This research is relevant to further outbreaks of
      contagious diseases as it sheds light on important aspects of the impact of
      public health interventions during emergencies and epidemics.

PMID- 28506276
TI  - Redo coronary bypass grafting for congenital left main coronary atresia: a case
      report.
AB  - BACKGROUND: Congenital left main coronary atresia is an extremely rare coronary
      anomaly. Long-term surgical outcomes and the optimal management strategies for
      recurrence of ischemia remain uncertain. Herein, we present a case involving
      successful redo coronary artery bypass grafting for unstable angina 27 years
      after the initial coronary artery bypass grafting for congenital left main
      coronary atresia. CASE PRESENTATION: A 33-year-old woman was referred to our
      department with unstable angina. At the age of 6, she had undergone coronary
      artery bypass grafting of the second diagonal branch using the left internal
      thoracic artery and the obtuse marginal branch using saphenous vein grafting for
      left main coronary atresia. Although a coronary angiogram showed a patent left
      internal thoracic artery graft to the second diagonal branch and a patent
      saphenous vein graft to the obtuse marginal branch, the left anterior descending
      artery was not being perfused by the grafts because of a disruption of blood flow
      to the left anterior descending artery from the left internal thoracic artery.
      Therefore, we performed a redo coronary artery bypass grafting using the in situ
      right internal thoracic artery to the first diagonal branch, which was to be
      connected to the left anterior descending artery, resulting in amelioration of
      the ischemia of the left anterior wall. The patient was discharged 10 days after
      the operation and has been in good health for over 3 years without recurrence of
      chest symptoms. CONCLUSIONS: Coronary revascularization using a saphenous vein
      and left internal thoracic artery grafts is effective in achieving an adequate
      blood supply to the distal coronary arteries, and this effect can last for
      decades. However, careful follow-up is necessary because recurrent myocardial
      ischemia due to the development of a coronary artery occlusion may occur in
      adulthood.

PMID- 28506275
TI  - Global survey of malaria rapid diagnostic test (RDT) sales, procurement and lot
      verification practices: assessing the use of the WHO-FIND Malaria RDT Evaluation
      Programme (2011-2014).
AB  - BACKGROUND: Malaria rapid diagnostic tests (RDTs) play a critical role in malaria
      case management, and assurance of quality is a key factor to promote good
      adherence to test results. Since 2007, the World Health Organization (WHO) and
      the Foundation for Innovative New Diagnostics (FIND) have coordinated a Malaria
      RDT Evaluation Programme, comprising a pre-purchase performance evaluation
      (product testing, PT) and a pre-distribution quality control of lots (lot
      testing, LT), the former being the basis of WHO recommendations for RDT
      procurement. Comprehensive information on malaria RDTs sold worldwide based on
      manufacturers' data and linked to independent performance data is currently not
      available, and detailed knowledge of procurement practices remains limited.
      METHODS: The use of the PT/LT Programme results as well as procurement and lot
      verification practices were assessed through a large-scale survey, gathering
      product-specific RDT sales and procurement data (2011-14 period) from a total of
      32 manufacturers, 12 procurers and 68 National Malaria Control Programmes
      (NMCPs). RESULTS: Manufacturers' reports showed that RDT sales had more than
      doubled over the four years, and confirmed a trend towards increased compliance
      with the WHO procurement criteria (from 83% in 2011 to 93% in 2014). Country
      level reports indicated that 74% of NMCPs procured only 'WHO-compliant' RDT
      products, although procurers' transactions datasets revealed a surprisingly
      frequent overlap of different products and even product types (e.g., Plasmodium
      falciparum-only and Plasmodium-pan) in the same year and country (60 and 46% of
      countries, respectively). Importantly, the proportion of 'non-complying' (i.e.,
      PT low scored or not evaluated) products was found to be higher in the private
      health care sector than in the public sector (32% vs 5%), and increasing over
      time (from 22% of private sector sales in 2011 to 39% in 2014). An estimated 70%
      of the RDT market was covered by the LT programme. The opinion about the PT/LT
      Programmes was positive overall, and quality of RDTs as per the PT Programme was
      rated as the number one procurement criteria. CONCLUSIONS: This survey provided
      in-depth information on RDT sales and procurement dynamics, including the largely
      unstudied private sector, and demonstrated how the WHO-FIND Programme has
      positively influenced procurement practices in the public sector.

PMID- 28506277
TI  - Quantifying the mapping precision of genome-wide association studies using whole
      genome sequencing data.
AB  - BACKGROUND: Understanding the mapping precision of genome-wide association
      studies (GWAS), that is the physical distances between the top associated single
      nucleotide polymorphisms (SNPs) and the causal variants, is essential to design
      fine-mapping experiments for complex traits and diseases. RESULTS: Using
      simulations based on whole-genome sequencing (WGS) data from 3642 unrelated
      individuals of European descent, we show that the association signals at rare
      causal variants (minor allele frequency <= 0.01) are very unlikely to be mapped
      to common variants in GWAS using either WGS data or imputed data and vice versa.
      We predict that at least 80% of the common variants identified from published
      GWAS using imputed data are within 33.5 Kbp of the causal variants, a resolution
      that is comparable with that using WGS data. Mapping precision at these loci will
      improve with increasing sample sizes of GWAS in the future. For rare variants,
      the mapping precision of GWAS using WGS data is extremely high, suggesting WGS is
      an efficient strategy to detect and fine-map rare variants simultaneously. We
      further assess the mapping precision by linkage disequilibrium between GWAS hits
      and causal variants and develop an online tool (gwasMP) to query our results with
      different thresholds of physical distance and/or linkage disequilibrium (
      http://cnsgenomics.com/shiny/gwasMP ). CONCLUSIONS: Our findings provide a
      benchmark to inform future design and development of fine-mapping experiments and
      technologies to pinpoint the causal variants at GWAS loci.

PMID- 28506278
TI  - A framework for evaluating epidemic forecasts.
AB  - BACKGROUND: Over the past few decades, numerous forecasting methods have been
      proposed in the field of epidemic forecasting. Such methods can be classified
      into different categories such as deterministic vs. probabilistic, comparative
      methods vs. generative methods, and so on. In some of the more popular
      comparative methods, researchers compare observed epidemiological data from the
      early stages of an outbreak with the output of proposed models to forecast the
      future trend and prevalence of the pandemic. A significant problem in this area
      is the lack of standard well-defined evaluation measures to select the best
      algorithm among different ones, as well as for selecting the best possible
      configuration for a particular algorithm. RESULTS: In this paper we present an
      evaluation framework which allows for combining different features, error
      measures, and ranking schema to evaluate forecasts. We describe the various
      epidemic features (Epi-features) included to characterize the output of
      forecasting methods and provide suitable error measures that could be used to
      evaluate the accuracy of the methods with respect to these Epi-features. We focus
      on long-term predictions rather than short-term forecasting and demonstrate the
      utility of the framework by evaluating six forecasting methods for predicting
      influenza in the United States. Our results demonstrate that different error
      measures lead to different rankings even for a single Epi-feature. Further, our
      experimental analyses show that no single method dominates the rest in predicting
      all Epi-features when evaluated across error measures. As an alternative, we
      provide various Consensus Ranking schema that summarize individual rankings, thus
      accounting for different error measures. Since each Epi-feature presents a
      different aspect of the epidemic, multiple methods need to be combined to provide
      a comprehensive forecast. Thus we call for a more nuanced approach while
      evaluating epidemic forecasts and we believe that a comprehensive evaluation
      framework, as presented in this paper, will add value to the computational
      epidemiology community.

PMID- 28506279
TI  - Uncovering the trimethylamine-producing bacteria of the human gut microbiota.
AB  - BACKGROUND: Trimethylamine (TMA), produced by the gut microbiota from dietary
      quaternary amines (mainly choline and carnitine), is associated with
      atherosclerosis and severe cardiovascular disease. Currently, little information
      on the composition of TMA producers in the gut is available due to their low
      abundance and the requirement of specific functional-based detection methods as
      many taxa show disparate abilities to produce that compound. RESULTS: In order to
      examine the TMA-forming potential of microbial communities, we established
      databases for the key genes of the main TMA-synthesis pathways, encoding choline
      TMA-lyase (cutC) and carnitine oxygenase (cntA), using a multi-level screening
      approach on 67,134 genomes revealing 1107 and 6738 candidates to exhibit cutC and
      cntA, respectively. Gene-targeted assays enumerating the TMA-producing community
      by quantitative PCR and characterizing its composition via Illumina sequencing
      were developed and applied on human fecal samples (n = 50) where all samples
      contained potential TMA producers (cutC was detected in all individuals, whereas
      only 26% harbored cntA) constituting, however, only a minor part of the total
      community (below 1% in most samples). Obtained cutC amplicons were associated
      with various taxa, in particular with Clostridium XIVa strains and Eubacterium
      sp. strain AB3007, though a bulk of sequences displayed low nucleotide identities
      to references (average 86% +/- 7%) indicating that key human TMA producers are
      yet to be isolated. Co-occurrence analysis revealed specific groups governing the
      community structure of cutC-exhibiting taxa across samples. CntA amplicons
      displayed high identities (~99%) to Gammaproteobacteria-derived references,
      primarily from Escherichia coli. Metagenomic analysis of samples provided by the
      Human Microbiome Project (n = 154) confirmed the abundance patterns as well as
      overall taxonomic compositions obtained with our assays, though at much lower
      resolution, whereas 16S ribosomal RNA gene sequence analysis could not adequately
      uncover the TMA-producing potential. CONCLUSIONS: In this study, we developed a
      diagnostic framework that enabled the quantification and comprehensive
      characterization of the TMA-producing potential in human fecal samples. The key
      players were identified, and together with predictions on their environmental
      niches using functional genomics on most closely related reference strains, we
      provide crucial information for the development of specific treatment strategies
      to restrain TMA producers and limit their proliferation.

PMID- 28506280
TI  - OptiMouse: a comprehensive open source program for reliable detection and
      analysis of mouse body and nose positions.
AB  - BACKGROUND: Accurate determination of mouse positions from video data is crucial
      for various types of behavioral analyses. While detection of body positions is
      straightforward, the correct identification of nose positions, usually more
      informative, is far more challenging. The difficulty is largely due to
      variability in mouse postures across frames. RESULTS: Here, we present OptiMouse,
      an extensively documented open-source MATLAB program providing comprehensive
      semiautomatic analysis of mouse position data. The emphasis in OptiMouse is
      placed on minimizing errors in position detection. This is achieved by allowing
      application of multiple detection algorithms to each video, including custom user
      defined algorithms, by selection of the optimal algorithm for each frame, and by
      correction when needed using interpolation or manual specification of positions.
      CONCLUSIONS: At a basic level, OptiMouse is a simple and comprehensive solution
      for analysis of position data. At an advanced level, it provides an open-source
      and expandable environment for a detailed analysis of mouse position data.

PMID- 28506281
TI  - A telephonic mindfulness-based intervention for persons with sickle cell disease:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: One of the most difficult symptoms for persons with sickle cell
      disease (SCD) to manage is chronic pain. Chronic pain impacts approximately one
      third of persons with SCD and is associated with increased pain intensity, pain
      behavior, and frequency and duration of hospital visits. A promising category of
      nonpharmacological interventions for managing both physical and affective
      components of pain are mindfulness-based interventions (MBIs). METHODS/DESIGN:
      The primary aim of this study is to conduct a randomized controlled study to
      evaluate the acceptability and feasibility, as well as to determine the
      preliminary efficacy, of a telephonic MBI for adults with SCD who have chronic
      pain. We will enroll 60 adult patients with SCD and chronic pain at an outpatient
      comprehensive SCD center in the southeastern United States. Patients will be
      randomized to either an MBI or a wait-listed control group. The MBI group will
      complete a six-session (60 minutes), telephonically delivered, group-based MBI
      program. The feasibility, acceptability, and efficacy of the MBI regarding pain
      catastrophizing will be assessed by administering questionnaires at baseline and
      weeks 1, 3, and 6. In addition, ten randomly selected MBI participants will
      complete semistructured interviews to help determine intervention acceptability.
      DISCUSSION: In this study protocol, we report detailed methods of the randomized
      controlled trial. Findings of this study will be useful to determine the
      acceptability, feasibility, and efficacy of an MBI for persons with SCD and
      chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02394587 .
      Registered on 9 February 2015.

PMID- 28506282
TI  - Under-triage in telephone consultation is related to non-normative symptom
      description and interpersonal communication: a mixed methods study.
AB  - BACKGROUND: Telephone consultation and triage are used to limit the workload on
      emergency departments. Lack of visual cues and clinical tests put telephone
      consultations to a disadvantage compared to face-to-face consultations increasing
      the risk of under-triage. Under-triage occurs in telephone triage; however why
      under-triage happens is not explored yet. The aim of the study was to describe
      situations of under-triage in context, to assess the quality of under-triaged
      calls, and to identify communication patterns contributing to under-triage in a
      regional OOH service in the capital region of Denmark. METHODS: Explanatory
      simultaneous mixed method with thematic analysis and descriptive statistics was
      chosen. The study was carried out in an Out-Of-Hours service (OOH) in the Capital
      Region of Denmark, Copenhagen. Under-triage was defined as Potentially Under
      Triaged Calls (PUTC) by specific criteria to an OOH Hotline, and identification
      by integration of three databases: Medical Hotline database, Emergency number
      database, including the Ambulance database, and electronic patient records.
      Distribution of PUTC were carried out using ICD-10 codes to identify diagnosis
      and main themes identified by qualitative analysis of audio recorded under
      triaged calls. Study period was October 15th to November 30th 2014. RESULTS:
      Three hundred twenty seven PUTC were identified, representing 0.04% of all calls
      (n = 937.056) to the OOH. Distribution of PUTC according to diagnoses was:
      digestive (24%), circulatory (19%), respiratory (15%) and all others (42%).
      Thematic analysis of the voice logs suggested that inadequate communication and
      non-normative symptom description contributed to under-triage. DISCUSSION: The
      incidence of potentially under-triage is low (0.04%). However, the over
      representation of digestive, circulatory, and respiratory diagnoses might suggest
      that under-triage is related to inadequate symptom description. We recommend that
      caller and call-handler collaborate systematically on problem identification and
      negotiate non-normative symptom description. CONCLUSION: The incidence of under
      triage is low (0.04%). However, the over-representation of digestive,
      circulatory, and respiratory diagnoses might suggest that under-triage is related
      to inadequate symptom description. We recommend that caller and call-handler
      collaborate systematically on problem identification and negotiate non-normative
      symptom description.

PMID- 28506285
TI  - Centralised versus local measurement of glycated haemoglobin in clinical trial
      settings: a comment on Arch et al., Trials. 2016.
AB  - Arch and colleagues in their 24 October 2016 paper in Trials focus on the issue
      of centralised versus local measurement of glycated haemoglobin (HbA1c) in
      clinical trial settings. Resolution of the debate is important: while local HbA1c
      measurement is less costly, and would thereby ease the stretched funding
      situations for clinical trials worldwide, it cannot be implemented at the expense
      of clinically unacceptable disparities between centralised and localised
      measurements. Arch and colleagues favour centralised measurement in their paper's
      conclusion. However, critical questions regarding the methods require a closer
      look. In this letter, we discuss some of the issues that the authors could
      clarify in order that the reader can agree (or disagree) to their inference with
      greater confidence.

PMID- 28506283
TI  - Prolactin blocks the expression of receptor activator of nuclear factor kappaB
      ligand and reduces osteoclastogenesis and bone loss in murine inflammatory
      arthritis.
AB  - BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and
      bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA).
      Here, we investigate the mechanism of PRL protection against bone loss in AIA and
      in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss,
      and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via
      osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not
      (Prlr+/+) for the PRL receptor. To help define target cells, synovial fibroblasts
      from Prlr+/+ mice were treated or not with proinflammatory cytokines ((Cyt),
      including TNFalpha, IL-1beta, and interferon (IFN)gamma) with or without PRL, and
      these synovial cells were co-cultured or not with bone marrow osteoclast
      progenitors from Prlr+/+ or Prlr-/- mice. RESULTS: In AIA, PRL treatment reduced
      joint swelling, increased trabecular bone area, lowered osteoclast density, and
      reduced mRNA levels of osteoclast-associated genes (tartrate-resistant acid
      phosphatase (Trap)), cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and
      receptor activator of nuclear factor kappaB or RANK (Tnfrsf11a)), of genes
      encoding cytokines with osteoclastogenic activity (Tnfa, Il1b, Il6, and receptor
      activator of nuclear factor kappaB ligand or RANKL (Tnfrsf11)), and of genes
      encoding for transcription factors and cytokines related to T helper (Th)17 cells
      (Rora, Rorc, Il17a, Il21, Il22) and to regulatory T cells (Foxp3, Ebi3, Il12a,
      Tgfb1, Il10). Prlr-/- mice with MAIA showed enhanced joint swelling, reduced
      trabecular bone area, increased osteoclast density, and elevated expression of
      Tnfa, Il1b, Il6, Trap, Tnfrsf11a, Tnfrsf11, Il17a, Il21, Il22, 1 l23, Foxp3, and
      Il10. The expression of the long PRL receptor form increased in arthritic joints,
      and in synovial membranes and cultured synovial fibroblasts treated with Cyt. PRL
      induced the phosphorylation/activation of signal transducer and activator of
      transcription-3 (STAT3) and inhibited the Cyt-induced expression of Il1b, Il6,
      and Tnfrsf11 in synovial fibroblast cultures. The STAT3 inhibitor S31-201 blocked
      inhibition of Tnfrsf11 by PRL. Finally, PRL acted on both synovial fibroblasts
      and osteoclast precursor cells to downregulate Cyt-induced osteoclast
      differentiation. CONCLUSION: PRL protects against osteoclastogenesis and bone
      loss in inflammatory arthritis by inhibiting cytokine-induced expression of RANKL
      in joints and synovial fibroblasts via its canonical STAT3 signaling pathway.

PMID- 28506284
TI  - The INVEST project: investigating the use of evidence synthesis in the design and
      analysis of clinical trials.
AB  - BACKGROUND: When designing and analysing clinical trials, using previous relevant
      information, perhaps in the form of evidence syntheses, can reduce research
      waste. We conducted the INVEST (INVestigating the use of Evidence Synthesis in
      the design and analysis of clinical Trials) survey to summarise the current use
      of evidence synthesis in trial design and analysis, to capture opinions of
      trialists and methodologists on such use, and to understand any barriers.
      METHODS: Our sampling frame was all delegates attending the International
      Clinical Trials Methodology Conference in November 2015. Respondents were asked
      to indicate (1) their views on the use of evidence synthesis in trial design and
      analysis, (2) their own use during the past 10 years and (3) the three greatest
      barriers to use in practice. RESULTS: Of approximately 638 attendees of the
      conference, 106 (17%) completed the survey, half of whom were statisticians.
      Support was generally high for using a description of previous evidence, a
      systematic review or a meta-analysis in trial design. Generally, respondents did
      not seem to be using evidence syntheses as often as they felt they should. For
      example, only 50% (42/84 relevant respondents) had used a meta-analysis to inform
      whether a trial is needed compared with 74% (62/84) indicating that this is
      desirable. Only 6% (5/81 relevant respondents) had used a value of information
      analysis to inform sample size calculations versus 22% (18/81) indicating support
      for this. Surprisingly large numbers of participants indicated support for, and
      previous use of, evidence syntheses in trial analysis. For example, 79% (79/100)
      of respondents indicated that external information about the treatment effect
      should be used to inform aspects of the analysis. The greatest perceived barrier
      to using evidence synthesis methods in trial design or analysis was time
      constraints, followed by a belief that the new trial was the first in the area.
      CONCLUSIONS: Evidence syntheses can be resource-intensive, but their use in
      informing the design, conduct and analysis of clinical trials is widely
      considered desirable. We advocate additional research, training and investment in
      resources dedicated to ways in which evidence syntheses can be undertaken more
      efficiently, offering the potential for cost savings in the long term.

PMID- 28506286
TI  - High protein intake without concerns?
AB  - The high fashion in nutrition for the critically ill is to recommend a high
      protein intake. Several opinion leaders are surfing on this wave, expanding the
      suggested protein allowance upwards. At the same time, there is no new evidence
      supporting this change in recommendations. Observational data show that in
      clinical practice protein intake is most often far below current ESPEN
      recommendations of 1.2-1.5 g/kg/day. Therefore, it may be in the best interests
      of our patients just to adhere to that guideline, and not to stretch them upwards
      for protein intake? Here we give arguments to stay conservative.

PMID- 28506287
TI  - Long-term outcomes of 307 patients after complete thymoma resection.
AB  - BACKGROUND: Thymoma is an uncommon tumor without a widely accepted standard care
      to date. We aimed to investigate the clinicopathologic variables of patients with
      thymoma and identify possible predictors of survival and recurrence after initial
      resection. METHODS: We retrospectively selected 307 patients with thymoma who
      underwent complete resection at the Cancer Hospital, Chinese Academy of Medical
      Sciences and Peking Union Medical College (Beijing, China) between January 2003
      and December 2014. The associations of patients' clinical characteristics with
      prognosis were estimated using Cox regression and Kaplan-Meier survival analyses.
      RESULTS: During follow-up (median, 86 months; range, 24-160 months), the 5- and
      10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and
      the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%,
      respectively. Masaoka stage (P < 0.001), World Health Organization (WHO)
      histological classification (P < 0.001), and postoperative radiotherapy after
      initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%).
      Multivariate analysis revealed that, after initial resection, WHO histological
      classification and Masaoka stage were independent predictors of DFS and OS. The
      pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional
      recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence
      pattern was an independent predictor of post-recurrence survival. Patients with
      recurrent thymoma who underwent repeated resection had increased post-recurrence
      survival rates compared with those who underwent therapies other than surgery (P
      = 0.017). CONCLUSIONS: Masaoka stage and WHO histological classification were
      independent prognostic factors of thymoma after initial complete resection. The
      recurrence pattern was an independent predictor of post-recurrence survival.
      Locoregional recurrence and repeated resection of the recurrent tumor were
      associated with favorable prognosis.

PMID- 28506288
TI  - Visualizing statistical significance of disease clusters using cartograms.
AB  - BACKGROUND: Health officials and epidemiological researchers often use maps of
      disease rates to identify potential disease clusters. Because these maps
      exaggerate the prominence of low-density districts and hide potential clusters in
      urban (high-density) areas, many researchers have used density-equalizing maps
      (cartograms) as a basis for epidemiological mapping. However, we do not have
      existing guidelines for visual assessment of statistical uncertainty. To address
      this shortcoming, we develop techniques for visual determination of statistical
      significance of clusters spanning one or more districts on a cartogram. We
      developed the techniques within a geovisual analytics framework that does not
      rely on automated significance testing, and can therefore facilitate visual
      analysis to detect clusters that automated techniques might miss. RESULTS: On a
      cartogram of the at-risk population, the statistical significance of a disease
      cluster is determinate from the rate, area and shape of the cluster under
      standard hypothesis testing scenarios. We develop formulae to determine, for a
      given rate, the area required for statistical significance of a priori and a
      posteriori designated regions under certain test assumptions. Uniquely, our
      approach enables dynamic inference of aggregate regions formed by combining
      individual districts. The method is implemented in interactive tools that provide
      choropleth mapping, automated legend construction and dynamic search tools to
      facilitate cluster detection and assessment of the validity of tested
      assumptions. A case study of leukemia incidence analysis in California
      demonstrates the ability to visually distinguish between statistically
      significant and insignificant regions. CONCLUSION: The proposed geovisual
      analytics approach enables intuitive visual assessment of statistical
      significance of arbitrarily defined regions on a cartogram. Our research prompts
      a broader discussion of the role of geovisual exploratory analyses in disease
      mapping and the appropriate framework for visually assessing the statistical
      significance of spatial clusters.

PMID- 28506289
TI  - A preliminary investigation to explore the cognitive resources of physicians
      experiencing difficulty in training.
AB  - BACKGROUND: Treating patients is complex, and research shows that there are
      differences in cognitive resources between physicians who experience
      difficulties, and those who do not. It is possible that differences in some
      cognitive resources could explain the difficulties faced by some physicians. In
      this study, we explore differences in cognitive resources between different
      groups of physicians (that is, between native (UK) physicians and International
      Medical Graduates (IMG); those who continue with training versus those who were
      subsequently removed from the training programme); and also between physicians
      experiencing difficulties compared with the general population. METHODS: A
      secondary evaluation was conducted on an anonymised dataset provided by the East
      Midlands Professional Support Unit (PSU). One hundred and twenty one postgraduate
      trainee physicians took part in an Educational Psychology assessment through PSU.
      Referrals to the PSU were mainly on the basis of problems with exam progression
      and difficulties in communication skills, organisation and confidence. Cognitive
      resources were assessed using the Wechsler Adult Intelligence Scale (WAIS-IV).
      Physicians were categorised into three PSU outcomes: 'Continued in training',
      'Removed from training' and 'Active' (currently accessing the PSU). RESULTS:
      Using a one-sample Z test, we compared the referred physician sample to a UK
      general population sample on the WAIS-IV and found the referred sample
      significantly higher in Verbal Comprehension (VCI; z = 8.78) and significantly
      lower in Working Memory (WMI; z = -4.59). In addition, the native sample were
      significantly higher in Verbal Comprehension than the UK general population
      sample (VCI; native physicians: z = 9.95, p < .001, d = 1.25), whilst there was a
      lesser effect for the difference between the IMG sample and the UK general
      population (z = 2.13, p = .03, d = 0.29). Findings also showed a significant
      difference in VCI scores between those physicians who were 'Removed from
      training' and those who 'Continued in training'. CONCLUSIONS: Our results suggest
      it is important to understand the cognitive resources of physicians to provide a
      more focussed explanation of those who experience difficulties in training. This
      will help to implement more targeted interventions to help physicians develop
      compensatory strategies.

PMID- 28506290
TI  - Pre-admission functional status impacts the performance of the APACHE IV model of
      mortality prediction in critically ill patients.
AB  - BACKGROUND: Functional status (FS) before intensive care unit (ICU) admission is
      associated with short-term and long-term outcomes among critically ill patients.
      However, measures of FS are generally not integrated into ICU-specific mortality
      prediction models. METHODS: This retrospective cohort study used prospectively
      collected data from 9638 consecutive patients admitted to a single ICU between 1
      October 2005 and 30 September 2015. For each ICU admission, FS was prospectively
      determined and classified into three discrete categories based on performance of
      basic daily living activities (FS1 - fully independent; FS2 - partly dependent;
      FS3 - completely dependent). We prospectively calculated Acute Physiology and
      Chronic Health Evaluation (APACHE) IV predicted mortality percentage (APIV PM)
      for each admission and calculated observed-expected mortality ratios (OEMR),
      stratified by FS category and APIV PM. We calculated area under the receiver
      operator characteristic curve (AUC) for APIV PM and mortality for the entire
      cohort and the three FS categories. RESULTS: Patients had a median (IQR) age of
      67 (52-80) years and mean (SD) APIV PM was 18.3% (24.3%). Of these, 7714 (80.0%)
      were classified as FS1, 1728 (17.9%) as FS2 and 196 (2.0%) as FS3. FS1 patients
      were younger, had less comorbid disease, and lower APIV PM compared to FS2 and
      FS3. The OEMR were significantly lower for FS1 (0.67) than FS2 (0.93) or FS3
      (0.90) (p < 0.0001 for both comparisons). Among patients with APIV PM 0-10%, 10
      25%, 25-50% and >=50% the OEMR for FS1 were 0.33, 0.49, 0.61 and 0.86. The AUC
      (95% CI) for APIV PM and mortality for FS1, FS2 and FS3 were 0.924 (0.914-0.933),
      0.837 (0.816-0.858) and 0.775 (0.705-0.8456), respectively (p < 0.001 for each
      comparison). Multivariable analysis demonstrated that FS2 (OR 2.18 (1.84-2.57) (p
      < 0.0001)) and FS3 (OR 1.99 (1.34-2.96) (p = 0.0006)) were independently
      associated with increased risk of mortality. CONCLUSIONS: Baseline FS prior to
      critical illness is a strong independent predictor of mortality and impacts the
      relationship between observed and APIV PM in those with lower illness severity.
      Future iterations of mortality prediction models should integrate a baseline
      measure of FS to improve performance.

PMID- 28506292
TI  - Normobaric hypoxia overnight impairs cognitive reaction time.
AB  - BACKGROUND: Impaired reaction time in patients suffering from hypoxia during
      sleep, caused by sleep breathing disorders, is a well-described phenomenon. High
      altitude sleep is known to induce periodic breathing with central apneas and
      oxygen desaturations, even in perfectly healthy subjects. However, deficits in
      reaction time in mountaineers or workers after just some nights of hypoxia
      exposure are not sufficiently explored. Therefore, we aimed to investigate the
      impact of sleep in a normobaric hypoxic environment on reaction time divided by
      its cognitive and motoric components. Eleven healthy non acclimatized students
      (5f, 6m, 21 +/- 2.1 years) slept one night at a simulated altitude of 3500 m in a
      normobaric hypoxic room, followed by a night with polysomnography at simulated
      5500 m. Preexisting sleep disorders were excluded via BERLIN questionnaire. All
      subjects performed a choice reaction test (SCHUHFRIED RT, S3) at 450 m and
      directly after the nights at simulated 3500 and 5500 m. RESULTS: We found a
      significant increase of cognitive reaction time with higher altitude (p = 0.026).
      No changes were detected in movement time (p = n.s.). Reaction time, the combined
      parameter of cognitive- and motoric reaction time, didn't change either (p =
      n.s.). Lower SpO2 surprisingly correlated significantly with shorter cognitive
      reaction time (r = 0.78, p = 0.004). Sleep stage distribution and arousals at
      5500 m didn't correlate with reaction time, cognitive reaction time or movement
      time. CONCLUSION: Sleep in hypoxia does not seem to affect reaction time to
      simple tasks. The component of cognitive reaction time is increasingly delayed
      whereas motoric reaction time seems not to be affected. Low SpO2 and arousals are
      not related to increased cognitive reaction time therefore the causality remains
      unclear. The fact of increased cognitive reaction time after sleep in hypoxia,
      considering high altitude workers and mountaineering operations with overnight
      stays, should be further investigated.

PMID- 28506291
TI  - Targeting CD22 with the monoclonal antibody epratuzumab modulates human B-cell
      maturation and cytokine production in response to Toll-like receptor 7 (TLR7) and
      B-cell receptor (BCR) signaling.
AB  - BACKGROUND: Abnormal B-cell activation is implicated in the pathogenesis of
      autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell
      surface molecule CD22, which regulates activation through the B-cell receptor
      (BCR), is a potential target for inhibiting pathogenic B cells; however, the
      regulatory functions of CD22 remain poorly understood. In this study, we
      determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22
      IgG1 monoclonal antibody, affects the activation of human B-cell subsets in
      response to Toll-like receptor 7 (TLR7) and BCR engagement. METHODS: B-cell
      subsets were isolated from human tonsils and stimulated with F(ab')2 anti-human
      IgM and/or the TLR7 agonist R848 in the presence of Emab or a human IgG1 isotype
      control. Changes in mRNA levels of genes associated with B-cell activation and
      differentiation were analyzed by quantitative PCR. Cytokine production was
      measured by ELISA. Cell proliferation, survival, and differentiation were
      assessed by flow cytometry. RESULTS: Pretreatment of phenotypically naive
      CD19+CD10-CD27- cells with Emab led to a significant increase in IL-10
      expression, and in some but not all patient samples to a reduction of IL-6
      production in response to TLR7 stimulation alone or in combination with anti-IgM.
      Emab selectively inhibited the expression of PRDM1, the gene encoding B
      lymphocyte-induced maturation protein 1 (Blimp-1) in activated CD10-CD27- B
      cells. CD10-CD27-IgD- cells were highly responsive to stimulation through TLR7 as
      evidenced by the appearance of blasting CD27hiCD38hi cells. Emab significantly
      inhibited the activation and differentiation of CD10-CD27-IgD- B cells into
      plasma cells. CONCLUSIONS: Emab can both regulate cytokine expression and block
      Blimp1-dependent B-cell differentiation, although the effects of Emab may depend
      on the stage of B-cell development or activation. In addition, Emab inhibits the
      activation of CD27-IgD- tonsillar cells, which correspond to so-called double
      negative memory B cells, known to be increased in SLE patients with more active
      disease. These data may be relevant to the therapeutic effect of Emab in vivo via
      modulation of the production of pro-inflammatory and anti-inflammatory cytokines
      by B cells. Because Blimp-1 is required by B cells to mature into antibody
      producing cells, inhibition of Blimp1 may reduce autoantibody production.

PMID- 28506293
TI  - Case report of unexpected gastrointestinal involvement in type 1 Gaucher disease:
      comparison of eliglustat tartrate treatment and enzyme replacement therapy.
AB  - BACKGROUND: Gastrointestinal involvement in Gaucher disease is very rare, and
      appears to be unresponsive to enzyme replacement therapy (ERT). CASE
      PRESENTATION: Here, we describe identical twin, splenectomized, non-neuronopathic
      Gaucher patients on long-term ERT for 9 years, who complained of epigastric
      discomfort due to Gaucher cell infiltration of the gastroduodenal mucosa. Rare
      compound heterozygous mutations (p.Arg48Trp and p.Arg257Gln) of the GBA gene were
      found in both. Improvement in the gastroduodenal infiltration and reduced
      chitotriosidase levels were observed in one who switched to eliglustat tartrate
      for 1 year, whereas the other one who maintained ERT showed no improvement of
      chitotriosidase level and persistent duodenal lesions. CONCLUSION: This shows
      that eliglustat might be an effective treatment for Gaucher disease patients
      having lesions resistant to ERT.

PMID- 28506294
TI  - hSSB1 associates with and promotes stability of the BLM helicase.
AB  - BACKGROUND: Maintenance of genome stability is critical in human cells. Mutations
      in or loss of genome stability pathways can lead to a number of pathologies
      including cancer. hSSB1 is a critical DNA repair protein functioning in the
      repair and signalling of stalled DNA replication forks, double strand DNA breaks
      and oxidised DNA lesions. The BLM helicase is central to the repair of both
      collapsed DNA replication forks and double strand DNA breaks by homologous
      recombination. RESULTS: In this study, we demonstrate that hSSB1 and BLM helicase
      form a complex in cells and the interaction is altered in response to ionising
      radiation (IR). BLM and hSSB1 also co-localised at nuclear foci following IR
      induced double strand breaks and stalled replication forks. We show that hSSB1
      depleted cells contain less BLM protein and that this deficiency is due to
      proteasome mediated degradation of BLM. Consequently, there is a defect in
      recruitment of BLM to chromatin in response to ionising radiation-induced DSBs
      and to hydroxyurea-induced stalled and collapsed replication forks. CONCLUSIONS:
      Our data highlights that BLM helicase and hSSB1 function in a dynamic complex in
      cells and that this complex is likely required for BLM protein stability and
      function.

PMID- 28506295
TI  - Gender-specific predictors of at-risk adolescents' hazardous alcohol use-a cohort
      study.
AB  - BACKGROUND: Previous research has found strong associations between adolescents'
      hazardous alcohol use and their perception of peer behavior, as well as own
      spending money and a range of antisocial behaviors. However, there is
      insufficient evidence of gender-specific predictors among adolescents with
      elevated antisocial behavior and alcohol use to design effective selective
      interventions. The aims of this study were to test short-term predictors of Heavy
      Episodic Drinking (HED) and risk-use of alcohol among 12-18-year-old females and
      males with elevated externalizing and delinquent behavior, and alcohol use.
      METHODS: Eighty-five females, 77 males, and their parents, originally recruited
      for a parent intervention, were assessed at baseline and 6 months later with
      several validated instruments measuring externalizing and internalizing behavior,
      alcohol use, psychosocial distress, and delinquency. RESULTS: The perception of
      peer drinking significantly predicted both genders' HED and risk-use, and also
      externalizing behavior predicted female risk-use. Rule-breaking behavior and
      social problems predicted both HED and risk-use among males, while rule-breaking
      predicted female HED and social problems predicted female risk-use. The parents'
      ratings of externalizing behavior predicted only their sons' risk-use. Lastly, no
      differences in prediction strength were found to be statistically significant
      differences between genders. CONCLUSIONS: Females and males shared several
      predictors of hazardous alcohol use, and perception of peer drinking emerged as a
      strong predictor. This suggests that interventions may target both genders'
      hazardous use of alcohol, and should address peer-resisting skills.

PMID- 28506296
TI  - Worlds apart? A scoping review addressing different stakeholder perspectives on
      barriers to family involvement in the care for persons with severe mental
      illness.
AB  - BACKGROUND: Empirical evidence shows that family involvement (FI) can play a
      pivotal role in the coping and recovery of persons with severe mental illness
      (SMI). Nevertheless, various studies demonstrate that FI in mental healthcare
      services is often not (sufficiently) realized. In order to develop more insights,
      this scoping review gives an overview of how various stakeholders conceptualize,
      perceive and experience barriers to FI. Central questions are: 1) What are the
      main barriers to FI reported by the different key stakeholders (i.e. the persons
      with SMI, their families and the professionals, and 2) What are the differences
      and similarities between the various stakeholders' perspectives on these
      barriers. METHODS: A systematic search into primary studies regarding FI was
      conducted in four databases: Medline/Pubmed, Cinahl, PsychInfo and Web of
      Knowledge with the use of a PICO scheme. Thematic analysis focused on stakeholder
      perspectives (i.e. which stakeholder group reports the barrier) and types of
      barriers (i.e. which types of barriers are addressed). RESULTS: Thirty three
      studies were included. The main barriers reported by the stakeholder groups
      reveal important similarities and differences between the stakeholder groups and
      were related to: 1) the person with SMI, 2) the family, 3) the professionals, 4)
      the organization of care and 5) the culture-paradigm. DISCUSSION: Our stakeholder
      approach elicits the different stakeholders' concepts, presuppositions and
      experiences of barriers to FI, and gives fundamental insights on how to deal with
      barriers to FI. The stakeholders differing interpretations and perceptions of the
      barriers related to FI is closely related to the inherent complexity involved in
      FI in itself. In order to deal better with these barriers, openly discussing and
      reflecting upon each other's normative understandings of barriers is needed.
      CONCLUSIONS: Differences in perceptions of barriers to FI can itself be a
      barrier. To deal with barriers to FI, a dialogical approach on how the different
      stakeholders perceive and value FI and its barriers is required. Methods such as
      moral case deliberation or systematic ethics reflections can be useful.

PMID- 28506297
TI  - Cervical cancer treatment costs and cost-effectiveness analysis of human
      papillomavirus vaccination in Vietnam: a PRIME modeling study.
AB  - BACKGROUND: Cervical cancer is currently the leading cause of cancer mortality
      among women in South Vietnam and the second leading cause of cancer mortality in
      North Vietnam. Human papillomavirus (HPV) vaccination has the potential to
      substantially decrease this burden. The World Health Organization (WHO)
      recommends that a cost-effectiveness analysis of HPV vaccination is conducted
      before nationwide introduction. METHODS: The Papillomavirus Rapid Interface for
      Modeling and Economics (PRIME) model was used to evaluate the cost-effectiveness
      of HPV vaccine introduction. A costing study based on expert panel discussions,
      interviews and hospital case note reviews was conducted to explore the cost of
      cervical cancer care. RESULTS: The cost of cervical cancer treatment ranged from
      US$368 - 11400 depending on the type of hospital and treatment involved. Under
      Gavi-negotiated prices of US$4.55, HPV vaccination is likely to be very cost
      effective with an incremental cost per disability-adjusted life year (DALY)
      averted in the range US$780 - 1120. However, under list prices for Cervarix and
      Gardasil in Vietnam, the incremental cost per DALY averted for HPV vaccination
      can exceed US$8000. CONCLUSION: HPV vaccine introduction appears to be
      economically attractive only if Vietnam is able to procure the vaccine at Gavi
      prices. This highlights the importance of initiating a nationwide vaccination
      programme while such prices are still available.

PMID- 28506298
TI  - FecX Bar a Novel BMP15 mutation responsible for prolificacy and female sterility
      in Tunisian Barbarine Sheep.
AB  - BACKGROUND: Naturally occurring mutations in growth and differentiation factor 9
      (GDF9) or bone morphogenetic protein 15 (BMP15) genes are associated with
      increased ovulation rate (OR) and litter size (LS) but also sterility. Observing
      the Tunisian Barbarine ewes of the "W" flock selected for improved prolificacy,
      we found prolific and infertile ewes with streaky ovaries. Blood genomic DNA was
      extracted from a subset of low-ovulating, prolific and infertile ewes of the "W"
      flock, and the entire coding sequences of GDF9 and BMP15 were sequenced. RESULTS:
      We evidenced a novel polymorphism in the exon 1 of the BMP15 gene associated with
      increased prolificacy and sterility. This novel mutation called FecX Bar is a
      composite polymorphism associating a single nucleotide substitution (c.301G > T),
      a 3 bp deletion (c.302_304delCTA) and a C insertion (c.310insC) in the ovine
      BMP15 cDNA leading to a frame shift at protein position 101. Calculated in the
      "W" flock, the FecX Bar allele increased OR by 0.7 ova and LS by 0.3 lambs (p =
      0.08). As for already identified mutations, homozygous females carrying FecX Bar
      exhibited streaky ovaries with a blockade at the primary stage of
      folliculogenesis as shown by histochemistry. CONCLUSIONS: Our investigation
      demonstrates a new mutation in the BMP15 gene providing a valuable genetic tool
      to control fecundity in Tunisian Barbarine, usable for diffusion program into
      conventional flocks looking for prolificacy improvement.

PMID- 28506299
TI  - Developmental hip dysplasia treated by total hip arthroplasty using a cementless
      Wagner cone stem in young adult patients with a small physique.
AB  - BACKGROUND: Developmental hip dysplasia (DDH) may lead to severe acetabular and
      femoral abnormalities that can render total hip arthroplasty (THA) challenging,
      especially in DDH patients with a small physique. Most conventional cemented or
      cementless femoral components are often difficult to implant in the narrow
      femoral canal and require slight version correction during surgery. The aim of
      this study was to present the mid-term results of THA in the treatment of DDH
      patients with a small physique using a cementless Wagner cone prosthesis
      (Zimmer(r), US). METHODS: Between January 2006 and March 2010, we retrospectively
      reviewed 50 patients who were treated at our center. A total of 50 patients (52
      hips; 45 women, five men; mean age 32.5 years; range 27 to 38 years) who
      underwent THA were observed. The mean femoral medullary canal dimension at the
      isthmus was 7.6 mm (range 6.0 to 8.7). According to the Crowe classification, 19
      hips presented dysplasia of grade I, while 33 presented dysplasia of grade II.
      All patients were treated with THA using a cementless Wagner cone prosthesis.
      Clinical and radiologic evaluations were performed on all patients. RESULTS: The
      mean duration of follow-up was 7.7 years (range 5.4 to 10.5). The Harris hip
      score (HHS) improved from 63 +/- 9 (range 55 to 70) pre-operatively to 92 +/- 8
      (range 88 to 100) at the last follow-up. The HHS at the most recent follow-up was
      excellent in 66% of patients (34 hips), good in 26% (14 hips), fair in 6% (3
      hips), and poor in 2% (1 hip). Radiographic evaluation demonstrated excellent
      osteointegration of the implants. Stem subsidence was present in three stems, and
      the range of stem subsidence was 2 mm in two stems (3.9%) and 3 mm in one stem
      (1.9%). Femoral osteolysis was observed in nine hips (18%) in the proximal zones,
      and no distal osteolysis was noted. Heterotopic ossification was observed in
      three hips (5.8%); of these, two were classified as Brooker's grade 1, and one
      was classified as Brooker's grade 2 at the most recent follow-up. None of the
      implants were revised. CONCLUSIONS: Based on the tapered shape and free setting
      of anteversion, the Wagner cone femoral stem facilitates its implantation in
      dysplastic hips. Therefore, this series of short stems with a smaller diameter
      can ensure safe implantation in narrow medullary canals, especially in young DDH
      patients with a small physique. TRIAL REGISTRATION: Registration Number: ChiCTR
      ORC-17011181 . Reg Date: 2017-04-19 00:44:59 Retrospective registration.

PMID- 28506301
TI  - Diffuse non-midline glioma with H3F3A K27M mutation: a prognostic and treatment
      dilemma.

PMID- 28506300
TI  - Cross-cultural adaptation and psychometric analysis of the Arabic version of the
      oxford knee score in adult male with knee osteoarthritis.
AB  - BACKGROUND: There are varieties of self-assessment questionnaire used for the
      evaluation of pain, functional disability, and health related quality of life in
      individuals with knee osteoarthritis (OA). The present study intended to adapt
      and translate the oxford knee score into the Arabic and investigated its
      psychometric properties in adult male with knee OA. METHODS: Ninety-seven adult
      male (mean age 57.55 +/- 11.49 years) with knee OA participated. Patients were
      requested to complete the adapted Arabic version of the Oxford knee score (OKS
      Ar), reduced "Western Ontario and McMaster Universities Index (WOMAC)", and the
      Visual analogue scale (VAS). Patients were requested to complete 2nd form of OKS
      Ar at least 1 week apart to assess the reproducibility of the score. The OKS was
      adapted and translated into Arabic by two independent Arabic native speakers (one
      rehabilitation professional having experience of knee OA patients and another one
      a trained translator) according to the international guidelines. RESULTS: All the
      participants completed the 2nd form of OKS-Ar (Response rate 100%). Reliability
      and internal consistency was high with an ICC of 0.97, and the Cronbach's alpha
      coefficient of 0.987, respectively. A significant relationship between the OKS-Ar
      and the WOMAC and VAS scores confirmed the construct validity (p < 0.001). The
      standard error of measurement (SEM) and the minimum detectable change (MDC) were
      2.2 and 6.2, respectively. CONCLUSIONS: The adapted Arabic version of the OKS
      demonstrated acceptable psychometric properties, including reliability, internal
      consistency, and the validity. The present study indicates that the OKS-Ar is a
      suitable questionnaire to measure pain and physical function in the Arabic
      speaking adult male patients with knee OA.

PMID- 28506303
TI  - Erratum to: Contribution of Candida biomarkers and DNA detection for the
      diagnosis of invasive candidiasis in ICU patients with severe abdominal
      conditions.

PMID- 28506302
TI  - Quantification of gait in mitochondrial m.3243A > G patients: a validation study.
AB  - BACKGROUND: More than half of the patients harbouring the m.3243A > G mutation
      were found to have trouble maintaining balance when walking in a recent study by
      our group. Others demonstrated that these patients had an abnormal gait pattern,
      as quantified by gait analysis. Gait analysis is an emerging method to quantify
      subtle changes in walking pattern, also during therapeutic interventions.
      Therefore, we aimed to test the reliability and reproducibility of gait analysis
      and select the most suitable protocol for this group of patients using a GAITRite
      electronic walkway. Four different protocols were tested: normal walking, dual
      task, post exercise and after a ten minutes of rest. RESULTS: In total 36
      patients with the m.3243A > G mutation and 50 healthy controls were enrolled in
      this study. Overall high intra class correlation coefficients were found in all
      experimental conditions for both patients and healthy controls indicating good
      reproducibility. Marked differences in gait between patients and controls were
      observed and were in line with the only available exploratory study performed.
      There was a good correlation between both the overall NMDAS score, NMDAS subscale
      scores, both markers for disease severity, and specific gait parameters.
      CONCLUSIONS: The observed reliability of the test makes GAITRite a suitable
      instrument for intervention studies in patients with mitochondrial disease.

PMID- 28506304
TI  - Characterization of genetic aberrations in a single case of metastatic thymic
      adenocarcinoma.
AB  - BACKGROUND: Thymic adenocarcinoma is an extremely rare subtype of thymic
      epithelial tumors. Due to its rarity, there is currently no sequencing approach
      for thymic adenocarcinoma. METHODS: We performed whole exome and transcriptome
      sequencing on a case of thymic adenocarcinoma and performed subsequent validation
      using Sanger sequencing. RESULTS: The case of thymic adenocarcinoma showed
      aggressive behaviors with systemic bone metastases. We identified a high
      incidence of genetic aberrations, which included somatic mutations in RNASEL,
      PEG10, TNFSF15, TP53, TGFB2, and FAT1. Copy number analysis revealed a complex
      chromosomal rearrangement of chromosome 8, which resulted in gene fusion between
      MCM4 and SNTB1 and dramatic amplification of MYC and NDRG1. Focal deletion was
      detected at human leukocyte antigen (HLA) class II alleles, which was previously
      observed in thymic epithelial tumors. We further investigated fusion transcripts
      using RNA-seq data and found an intergenic splicing event between the CTBS and
      GNG5 transcript. Finally, enrichment analysis using all the variants represented
      the immune system dysfunction in thymic adenocarcinoma. CONCLUSION: Thymic
      adenocarcinoma shows highly malignant characteristics with alterations in several
      cancer-related genes.

PMID- 28506305
TI  - Effect of chemotherapy counseling by pharmacists on quality of life and
      psychological outcomes of oncology patients in Malaysia: a randomized control
      trial.
AB  - BACKGROUND: Cancer is now becoming a leading cause of death. Chemotherapy is an
      important treatment for cancer patients. These patients also need consultation
      during their treatment to improve quality of life and decrease psychological
      disorders. The objectives of the study were to develop, implement and evaluate
      the effectiveness of a chemotherapy counseling module by pharmacists among
      oncology patients on their quality of life and psychological outcomes in
      Malaysia. METHOD: A single-blind randomized controlled trial was carried out
      among 162 oncology patients undergoing chemotherapy from July 2013 to February
      2014 in a government hospital with oncology facilities in Malaysia. Participants
      were randomized to either the intervention group or the control group.
      Chemotherapy counseling using the module on 'Managing Patients on Chemotherapy'
      by Pharmacists was delivered to the intervention group. The outcome measures were
      assessed at baseline, first follow-up and second follow-up and third follow-up
      post-intervention. Chi-square, independent samples t-test and two-way repeated
      measures ANOVA were conducted in the course of the data analyses. RESULTS: In
      assessing the impact of the chemotherapy counseling module, the study revealed
      that the module along with repetitive counseling showed significant improvement
      of quality of life in the intervention group as compared to the control group
      with a large effect size in physical health (p = 0.001, partial N2 = 0.66),
      psychological (p = 0.001, partial N2 = 0.65), social relationships (p = 0.001,
      partial N2 = 0.30), and environment (p = 0.001, partial N2 = 0.67) and decrease
      in the anxiety (p = 0.000; partial N2 = 0.23), depression (p = 0.000; partial N2
      = 0.40). CONCLUSION: The module on 'Managing Patients on Chemotherapy' along with
      repetitive counseling by pharmacists has been shown to be effective in improving
      quality of life and decreasing anxiety and depression among oncology patients
      undergoing chemotherapy. TRIAL REGISTRATION NUMBER: National Medical Research
      Register (NMRR) of Malaysia and given a registration number NMRR-12-1057-12,363
      on 21 December 2012.

PMID- 28506306
TI  - Predictors of physical and mental health in persons with morbid obesity attending
      a patient education course - a two-year follow-up study.
AB  - BACKGROUND: People with morbid obesity (body mass index >=40) may experience
      changes in their health after participating in a tailored patient education
      course. The aims of this study were to assess the changes in physical and mental
      health in persons with morbid obesity during the 2 years following an educational
      course and to explore possible socio-demographic, treatment, and personal
      predictors of physical and mental health outcomes. METHODS: In this prospective
      longitudinal cohort study, self-report questionnaire data were collected from
      people with morbid obesity at the beginning of mandatory educational courses
      while on a waiting list for gastric surgery and at two-year follow-up. Of the 185
      who attended the courses, 142 (77%) volunteered to participate in the study, and
      the 59 with complete data at the two-year follow-up were included in the
      analysis. Physical and mental health were measured with the physical and mental
      component summary scores from the Short Form 12v2. Self-esteem was measured by
      the Rosenberg Self-Esteem Scale, and self-efficacy by the General Self-Efficacy
      Scale. RESULTS: The participants reported better physical health at two-year
      follow-up than at baseline. Mental health did not change significantly over time.
      Receiving surgical treatment during the study period predicted better physical
      health at two-year follow-up, even after controlling for physical health at
      baseline. Mental health at baseline was the only significant baseline predictor
      of mental health at follow-up. However, increasing self-esteem and self-efficacy
      over the two-year study period independently predicted better mental health at
      follow up after controlling for mental health at baseline. CONCLUSION: Our study
      showed that people with morbid obesity on a waiting list for bariatric surgery
      improved their physical health during the 2 years after attending a tailored
      patient educational course. Improving self-esteem and self-efficacy may be
      important personal factors for maintaining mental health during this period.
      TRIAL REGISTRATION: NCT01336725 . Registered 14 April 2011.

PMID- 28506307
TI  - Intestinal parasitic infections and its association with undernutrition and CD4 T
      cell levels among HIV/AIDS patients on HAART in Butajira, Ethiopia.
AB  - BACKGROUND: Intestinal parasitic infections and HIV/AIDS have been the major
      public health problems and remain a vital cause of morbidity and mortality in
      developing countries. Both problems are linked in a vicious cycle. The magnitude
      of intestinal parasites was prevalent among people living with HIV/AIDS even in
      the HAART era. However, the pertinent risk factors associated with intestinal
      parasites among HIV/AIDS patients were not well investigated in Ethiopia
      particularly at Butajira town. Therefore, the aim of this study was to determine
      the prevalence of intestinal parasites and associated risk factors among HIV/AIDS
      patients on HAART in Butajira, Ethiopia. METHOD: A cross-sectional study was
      conducted, and a total of 323 study subjects was involved in the study. A
      systematic random sampling technique was used to select each participant during
      data collection. Stool specimen was collected and processed using direct wet
      mount, formol-ether concentration technique, and modified Ziehl-Neelson staining
      techniques to identify both common and opportunistic intestinal parasites.
      Structured questionnaire was used to collect socio-demographic, environmental,
      clinical, and nutritional data. Both bivariate and multivariate logistic
      regression analyses were used to assess the association of various explanatory
      factors on intestinal parasites. P value <=0.05 at 95% CI was considered
      statistically significant. RESULTS: The overall prevalence of intestinal
      parasites was 35.9% (95% CI 31.0-40.9%). Protozoa's (Entanmoeba
      histolytica/dispar trophozoite, E. histolytica/dispar cyst, Giardia lamblia
      trophozoite, and G. lamblia cyst), helminths (Tanea species, Ascaris
      lumbricoides, Strongyloid stercoralis, Hookworm species and H. nana), and
      opportunistic intestinal parasites (Cryptosporidium parvum, Isospora belli) were
      observed in 57 (17.1%), 46 (14.4%), and 28 (8.7%) study participants
      respectively. Multivariate logistic regression analysis revealed that the
      presence of animals (AOR 6. 14; 95% CI 3.13, 12.0); using river water (AOR 4.87;
      95% CI 1.14, 20.7); undernutrition (AOR 2.59; 95% CI 1.36-4.95); and level of
      immunosuppression (AOR 4.02; 95% CI 1.78-9.05 and AOR 2.84; 95% CI 1.37-5.89)
      were significantly associated with intestinal parasites. CONCLUSIONS: The
      prevalence of intestinal parasites found to be higher among HIV/AIDS patients
      receiving HAART at Butajira Hospital, southern Ethiopia. Presence of animals,
      using river water, lower CD4 T cell count, and undernutrition were significant
      factors affecting intestinal parasites. Therefore, consistent detection of
      intestinal parasites and deworming of patients should be performed as well as
      improving health education on personal hygiene, avoiding contact with pit or
      domestic animals, and using safe or treated water. Furthermore, improving
      nutritional support and household food access are recommended.

PMID- 28506308
TI  - Attenuating immune pathology using a microbial-based intervention in a mouse
      model of cigarette smoke-induced lung inflammation.
AB  - BACKGROUND: Cigarette smoke exposure is the major risk factor for developing
      COPD. Presently, available COPD treatments focus on suppressing inflammation and
      providing bronchodilation. However, these options have varying efficacy in
      controlling symptoms and do not reverse or limit the progression of COPD.
      Treatments strategies using bacterial-derived products have shown promise in
      diseases characterized by inflammation and immune dysfunction. This study
      investigated for the first time whether a novel immunotherapy produced from
      inactivated Klebsiella (hereafter referred to as KB) containing all the major
      Klebsiella macromolecules, could attenuate cigarette smoke exposure-induced
      immune responses. We hypothesized that KB, by re-directing damaging immune
      responses, would attenuate cigarette smoke-induced lung inflammation and
      bronchoalveolar (BAL) cytokine and chemokine production. METHODS: KB was
      administered via a subcutaneous injection prophylactically before initiating a 3
      week acute nose-only cigarette smoke exposure protocol. Control mice received
      placebo injection and room air. Total BAL and differential cell numbers were
      enumerated. BAL and serum were analysed for 31 cytokines, chemokines, and growth
      factors. Lung tissue and blood were analysed for Ly6CHI monocytes/macrophages and
      neutrophils. Body weight and clinical scores were recorded throughout the
      experiment. RESULTS: We demonstrate that KB treatment attenuated cigarette smoke
      induced lung inflammation as shown by reductions in levels of BAL IFNgamma,
      CXCL9, CXCL10, CCL5, IL-6, G-CSF, and IL-17. KB additionally attenuated the
      quantity of BAL lymphocytes and macrophages. In parallel to the attenuation of
      lung inflammation, KB induced a systemic immune activation with increases in
      Ly6CHI monocytes/macrophages and neutrophils. CONCLUSIONS: This is the first
      demonstration that subcutaneous administration of a microbial-based immunotherapy
      can attenuate cigarette smoke-induced lung inflammation, and modulate BAL
      lymphocyte and macrophage levels, while inducing a systemic immune activation and
      mobilization. These data provide a foundation for future studies exploring how KB
      may be used to either reverse or prevent progression of established emphysema and
      small airways disease associated with chronic cigarette smoke exposure. The data
      suggest the intriguing possibility that KB, which stimulates rather than
      suppresses systemic immune responses, might be a novel means by which the course
      of COPD pathogenesis may be altered.

PMID- 28506309
TI  - Social isolation and cancer management - advanced rectal cancer with patient
      delay following the 2011 triple disaster in Fukushima, Japan: a case report.
AB  - BACKGROUND: Little is known about the effects of social isolation in the elderly
      on their process of gaining health information and seeking health care. CASE
      PRESENTATION: In March 2011, Fukushima, Japan experienced an earthquake, tsunami,
      and nuclear disaster, also known as Japan's triple disaster. In June 2016, an 80
      year-old Japanese man, who lived alone after divorce at the age of 42, presented
      to our hospital with bloody stools and dizziness. Although his bloody stools
      initially occurred in May 2015, a year earlier, he did not pursue the possibility
      of malignancy. He was diagnosed as having stage IIIA rectal cancer. Detailed
      history taking revealed that he experienced social isolation after the disaster,
      due to the evacuation of his friends, losing his regular opportunities for
      socialization. He additionally reported that the current diagnosis of rectal
      cancer made him feel he had lost his health in addition to his social
      relationships. Although radical surgery was attempted, it failed to resect the
      lesion completely, and thereafter his disease gradually progressed. As support
      from family or friends was not available, he was not able to receive palliative
      radiation therapy or home-based care in his end-of-life period. He died at a long
      term care facility in February 2017. CONCLUSIONS: This case suggests that intense
      social isolation after the Fukushima disaster was a likely contributor to the
      patient delay, poor treatment course, and poor outcome of an elderly patient with
      rectal cancer. Direct communication with family and friends may play an
      indispensable role in increasing health awareness and promoting health-seeking
      behaviors, and in the midst of social isolation, elderly patients with cancer may
      lose these opportunities and experience increased risk of patient delay. Although
      health care providers may be able to alleviate isolation-induced delay by
      promoting cancer knowledge and awareness widely among local residents, policy-led
      interventions at the community level may be essential to reducing social
      isolation and its health consequences.

PMID- 28506310
TI  - Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin
      receptor and TGF-beta/pSmad3.
AB  - BACKGROUND: shRNA lentiviral vectors are extensively used for gene knockdowns in
      mammalian cells, and non-target shRNAs typically are considered the proper
      experimental control for general changes caused by RNAi. However, the effects of
      non-target lentivirus controls on the modulation of cell signaling pathways
      remain largely unknown. In this study, we evaluated the effect of control
      lentiviral transduction on oxytocin receptor (OXTR) expression through the
      ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity,
      and in vivo on mouse muscle regeneration. Furthermore, we mined published data
      for the influence of viral infections on OXTR levels in human populations and
      found that unrelated viral pathologies have a common consequence: diminished
      levels of OXTR. METHODS: We examined the change in OXTR mRNA expression upon
      transduction with control and Smad3-targeting viral vectors through real time RT
      PCR and Western blotting, and confirmed with immunofluorescence. Changes in Smad3
      and OXTR expression were examined both in vitro with mouse and human myoblasts
      and in vivo in mouse satellite cells. The general effects of viral infections on
      OXTR downregulation in humans were also examined by analyzing published Gene
      Expression Omnibus (GEO) datasets. The change in myoblast myogenic activity
      caused by the viral transduction (the percent of Pax7 + Ki67+ cells) was examined
      by immunofluorescence. RESULTS: Results shown in this work establish that
      lentiviral control vectors significantly downregulate OXTR expression at mRNA and
      protein levels and diminish key downstream effectors of OXTR, ERK signaling,
      reducing the myogenic proliferation of infected cells. This effect is
      evolutionarily conserved between mouse and human myogenic cells, and it manifests
      in satellite cells after control lentiviral transduction of mice in vivo.
      Furthermore, an examination of published datasets uncovered similar OXTR
      downregulation in humans that are afflicted with different viral infections.
      Additionally, cells transduced with Smad3-targeting shRNA downregulate OXTR even
      more than cells transduced with control viruses. CONCLUSIONS: Our work suggests
      that experimental cohorts transduced with control viruses may not behave the same
      as un-transduced cells and animals, specifically that control viral vectors
      significantly change the intensity of key cell-signaling pathways, such as
      OXTR/ERK. Our results further demonstrate that lentiviral transduction
      significantly decreases myogenic proliferation and suggest that viral infections
      in general may play a role in decreasing muscle health and regeneration, a
      decline in metabolic health, and a lower sense of well-being, as these rely on
      effective OXTR signaling. Additionally, our data suggest pathway crosstalk
      between TGF-beta/pSmad3 and OXTR, implying that sustained attenuation of the TGF
      beta/pSmad3 pathway will reduce pro-regenerative OXTR/pERK signaling.

PMID- 28506311
TI  - One-fourth of the prisoners are underweight in Northern Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Despite the fact that prisoners are exposed to different health
      problems, prison health problems are often overlooked by researchers and no
      previous study has investigated nutritional problems of prisoners in Ethiopia.
      METHODS: Cross-sectional data were collected from 809 prisoners from nine major
      prison setups in the Tigray region of Ethiopia. A proportional stratified
      sampling technique was used to select the total number of participants needed
      from each prison site. The outcome of this study was underweight defined as body
      mass index (BMI) of less than 18.5 kg/m2. Multivariable binary logistic
      regression was performed to identify determinants of underweight at a p-value of
      less than 0.05. RESULTS: The prevalence of underweight was 25.2% (95% CI; 22.3%-
      28.3%). Khat Chewing (OR = 2.08; 95% CI = 1.17, 3.70) and longer duration of
      incarceration (OR = 1.07; 95% CI = 1.01, 1.14) were associated with a
      significantly increased risk of underweight. Additionally, previous incarceration
      (OR = 1.54; 95% CI = 0.99, 2.42) was a relevant determinant of underweight with a
      borderline significance. In contrast, family support (OR = 0.61; 95% CI = 0.43,
      0.85) and farmer occupation (OR = 0.59; 95% CI = 0.36, 0.98) compared to those
      who were unemployed were important protective determinants significantly
      associated with lower risk of underweight. CONCLUSION: In summary, the burden of
      underweight was higher among prisoners in Tigray region who had respiratory tract
      infections. The study has enhanced our understanding of the determinants of
      underweight in the prison population. We strongly recommend that nutritional 
      support , such as therapeutic feeding programs for severely or moderately
      underweight prisoners, and environmental health interventions of the prison
      setups should be urgently implemented to correct the uncovered nutritional
      problem and its associated factors for improving the health status of prisoners.

PMID- 28506313
TI  - Latent variable mixture models to test for differential item functioning: a
      population-based analysis.
AB  - BACKGROUND: Comparisons of population health status using self-report measures
      such as the SF-36 rest on the assumption that the measured items have a common
      interpretation across sub-groups. However, self-report measures may be sensitive
      to differential item functioning (DIF), which occurs when sub-groups with the
      same underlying health status have a different probability of item response. This
      study tested for DIF on the SF-36 physical functioning (PF) and mental health
      (MH) sub-scales in population-based data using latent variable mixture models
      (LVMMs). METHODS: Data were from the Canadian Multicentre Osteoporosis Study
      (CaMos), a prospective national cohort study. LVMMs were applied to the ten PF
      and five MH SF-36 items. A standard two-parameter graded response model with one
      latent class was compared to multi-class LVMMs. Multivariable logistic regression
      models with pseudo-class random draws characterized the latent classes on
      demographic and health variables. RESULTS: The CaMos cohort consisted of 9423
      respondents. A three-class LVMM fit the PF sub-scale, with class proportions of
      0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with
      class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting
      greater limitations were consistently higher in classes 2 and 3 than class 1. For
      MH items, respondents in class 2 reported more health problems than in class 1.
      Differences in item thresholds and factor loadings between one-class and multi
      class models were observed for both sub-scales. Demographic and health variables
      were associated with class membership. CONCLUSIONS: This study revealed DIF in
      population-based SF-36 data; the results suggest that PF and MH sub-scale scores
      may not be comparable across sub-groups defined by demographic and health status
      variables, although effects were frequently small to moderate in size. Evaluation
      of DIF should be a routine step when analysing population-based self-report data
      to ensure valid comparisons amongst sub-groups.

PMID- 28506312
TI  - Pathomimetic avatars reveal divergent roles of microenvironment in invasive
      transition of ductal carcinoma in situ.
AB  - BACKGROUND: The breast tumor microenvironment regulates progression of ductal
      carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is
      unclear how interactions between breast epithelial and stromal cells can drive
      this progression and whether there are reliable microenvironmental biomarkers to
      predict transition of DCIS to IDC. METHODS: We used xenograft mouse models and a
      3D pathomimetic model termed mammary architecture and microenvironment
      engineering (MAME) to study the interplay between human breast myoepithelial
      cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression.
      RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in
      vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the
      size of 3D DCIS structures and their degradation of extracellular matrix. We
      further show that the tumor-suppressive effects of MEPs on DCIS are linked to
      inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen
      activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor
      1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by
      attenuating interleukin 6 (IL-6) signaling pathways. CONCLUSIONS: Our studies
      using MAME are, to our knowledge, the first to demonstrate a divergent interplay
      between MEPs and CAFs within the DCIS tumor microenvironment. We show that the
      tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor,
      uPAR, and are sustained even in the presence of the CAFs, which themselves
      enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor
      microenvironmental regulators of DCIS progression will be critical for defining a
      robust and predictive molecular signature for clinical use.

PMID- 28506314
TI  - Application of intraoperative limb-length measurement by a new osteotomy device
      in hemiarthroplasty for treating femoral neck fracture.
AB  - BACKGROUND: Limb length discrepancy is one of the most common complications after
      hip arthroplasty. We developed a device - intraoperative limb-length measurement
      and osteotomy device (ILMOD), and applied it to patients who were treated with
      hemiarthroplasty for femoral neck fracture to improve limb length discrepancy by
      providing an accurate osteotomy during hemi-arthroplasty. METHODS: Between April
      2012 and October 2013, 65 patients were treated with hip hemiarthroplasty for
      femoral neck fracture at our trauma center. 31 patients met the inclusion
      criteria and were randomly enrolled into two groups ILMOD group and control
      group. Hemiarthroplasty in this study was performed with cement fixation.
      Treatment-related measurements such as the operation time, attempts of osteotomy,
      and the volume of intra-operative blood loss were collected. In both groups,
      postoperative (1 month) radiologic analysis on anteroposterior weight-bearing
      pelvic view was performed to evaluate limb length discrepancy. RESULTS: The
      results showed significant improvement in limb length discrepancy in ILMOD group,
      and analysis of postoperative radiographs found the mean length difference is 2.1
      +/- 1.9 mm in ILMOD group compared to 8.8 +/- 5.1 mm in control group (P <
      0.0001). No complications associated with the use of the device were reported,
      and none of the patients complained of the discomfort related to limb-length
      discrepancy after surgery. The average intra-operative time was significantly
      longer in ILMOD group (84.9 +/- 9.2 min) compared to that in control group (70.9
      +/- 10.2 min) (P = 0.0004). CONCLUSIONS: The ILMOD is an effective device that
      can be used easily for intraoperative limb length measurement and osteotomy
      during hemiarthroplasty. This method is applicable with Kocher-Langenbeck
      approach, and the technique could also be used in total hip arthroplasty. TRIAL
      REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OOC-15005904 . Registered 30
      Junuary 2015.

PMID- 28506315
TI  - Molecular mechanisms underlying osteoarthritis development: Notch and NF-kappaB.
AB  - Osteoarthritis (OA) is a multi-factorial and highly prevalent joint disorder
      worldwide. Since the establishment of murine surgical knee OA models in 2005,
      many of the key molecules and signalling pathways responsible for OA development
      have been identified. Here we review the roles of two multi-functional signalling
      pathways in OA development: Notch and nuclear factor kappa-light-chain-enhancer
      of activated B cells. Previous studies have identified various aspects of
      articular chondrocyte regulation by these pathways. However, comprehensive
      understanding of the molecular networks regulating articular cartilage
      homeostasis and OA pathogenesis is needed.

PMID- 28506316
TI  - Characterization of novel Omp31 antigenic epitopes of Brucella melitensis by
      monoclonal antibodies.
AB  - BACKGROUND: Brucellosis is a severe zoonotic disease worldwide. Detection and
      identification of Brucella species are essential to prevent or treat brucellosis
      in humans and animals. The outer membrane protein-31 (Omp31) is a major protein
      of Brucellae except for B. abortus, while the Omp31 antigenic epitopes have not
      been extensively characterized yet. RESULTS: A total of 22 monoclonal antibodies
      (mAbs) were produced against Omp31 of Brucella (B.) melitensis, of which 13
      recognized five linear epitopes, 7 reacted with semi-conformational epitopes and
      2 reacted with conformational epitopes, respectively. The mAb isotypes were 11
      (50%) IgG2a, 5 (23%) IgG1 and 6 (27%) IgM. On the basis of epitope recognition
      and reactivity levels, 8 mAbs including 3 IgM and 5 IgG clones were considered as
      highly reactive and potentially diagnostic antibodies. Among these mAbs, 7A3
      (IgG1), 5B1 (IgG2a), 2C1 (IgG2a) and 5B3 (IgG2a) reacted with differently
      conserved linear epitopes of B. melitensis, B. ovis, B. suis and B. canis
      strains, while 5H3 (IgG2a) highly reacted with a conformational epitope of Omp31
      when tested with several immunoassays. CONCLUSIONS: These potent monoclonal
      antibodies can be used for identifying Omp31 antigens or detecting B. melitensis
      and other Brucella species beyond B. abortus in vitro or in vivo.

PMID- 28506317
TI  - Changes in microbial ecology after fecal microbiota transplantation for recurrent
      C. difficile infection affected by underlying inflammatory bowel disease.
AB  - BACKGROUND: Gut microbiota play a key role in maintaining homeostasis in the
      human gut. Alterations in the gut microbial ecosystem predispose to Clostridium
      difficile infection (CDI) and gut inflammatory disorders such as inflammatory
      bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor
      can restore gut microbial diversity and pathogen colonization resistance;
      consequently, it is now being investigated for its ability to improve
      inflammatory gut conditions such as IBD. In this study, we investigated changes
      in gut microbiota following FMT in 38 patients with CDI with or without
      underlying IBD. RESULTS: There was a significant change in gut microbial
      composition towards the donor microbiota and an overall increase in microbial
      diversity consistent with previous studies after FMT. FMT was successful in
      treating CDI using a diverse set of donors, and varying degrees of donor stool
      engraftment suggesting that donor type and degree of engraftment are not drivers
      of a successful FMT treatment of CDI. However, patients with underlying IBD
      experienced an increased number of CDI relapses (during a 24-month follow-up) and
      a decreased growth of new taxa, as compared to the subjects without IBD.
      Moreover, the need for IBD therapy did not change following FMT. These results
      underscore the importance of the existing gut microbial landscape as a decisive
      factor to successfully treat CDI and potentially for improvement of the
      underlying pathophysiology in IBD. CONCLUSIONS: FMT leads to a significant change
      in microbial diversity in patients with recurrent CDI and complete resolution of
      symptoms. Stool donor type (related or unrelated) and degree of engraftment are
      not the key for successful treatment of CDI by FMT. However, CDI patients with
      IBD have higher proportion of the original community after FMT and lack of
      improvement of their IBD symptoms and increased episodes of CDI on long-term
      follow-up.

PMID- 28506318
TI  - The association between time scarcity, sociodemographic correlates and
      consumption of ultra-processed foods among parents in Norway: a cross-sectional
      study.
AB  - BACKGROUND: Use of ultra-processed foods has expanded rapidly over the last
      decades and high consumption has been positively associated with risk of e.g.
      overweight, obesity and type 2 diabetes. Ultra-processed foods offer convenience
      as they require minimal time for preparation. It is therefore reasonable to
      assume that such foods are consumed more often among people who experience time
      scarcity. The main aim of this study was to investigate the association between
      time scarcity and consumption of ultra-processed foods among parents of 2-year
      olds in Norway. A secondary aim was to investigate the association between
      sociodemographic correlates, weight status and consumption of ultra-processed
      foods. METHODS: This cross-sectional study included 497 participants. Chi-square
      and cross tabulations were used to calculate proportions of high vs. low
      consumption of ultra-processed foods in relation to time scarcity,
      sociodemographic correlates and weight status. Binary logistic regression
      analyses were performed to test the relationship between independent variables
      and consumption of ultra-processed foods. RESULTS: Participants reporting medium
      and high time scarcity were more likely to have a high consumption of ultra
      processed dinner products (OR = 3. 68, 95% CI = 2. 32-5.84 and OR = 3.10, 1.80
      5.35, respectively) and fast foods (OR = 2.60, 1.62-4.18 and OR = 1.90, 1.08
      3.32, respectively) compared to those with low time scarcity. Further,
      participants with medium time scarcity were more likely to have a high
      consumption of snacks and soft drinks compared to participants with low time
      scarcity (OR = 1.63, 1.06-2.49). Finally, gender, ethnicity, educational level,
      number of children in the household and weight status were identified as
      important factors associated with the consumption of certain types of ultra
      processed foods. CONCLUSIONS: Results from the present study showed that time
      scarcity, various sociodemographic factors and weight status was associated with
      consumption of processed foods. Future studies with a longitudinal design are
      needed to further explore these patterns over a longer period of time.

PMID- 28506319
TI  - Validation of the Italian version of the Laval questionnaire: health-related
      quality of life in subjects with obesity.
AB  - BACKGROUND: Obesity is associated to increased risk of metabolic comorbidity as
      well as increased mortality. Notably, obesity is also associated to the
      impairment of the psychological status and of quality of life. Only three
      questionnaires are available in the Italian language evaluating the health
      related quality of life in subjects with obesity. The aim of the present study
      was to test the validity and reliability of the Italian version of the Laval
      Questionnaire. METHODS: The original French version was translated into Italian
      and back-translated by a French native speaker. 273 subjects with obesity (Body
      Mass Index >= 30 kg/m2) were enrolled; the Italian version of the Laval
      Questionnaire and the O.R.Well-97 questionnaire were administered in order to
      assess health- related quality of life. The Laval questionnaire consists of 44
      items distributed in 6 domains (symptoms, activity/mobility, personal
      hygiene/clothing, emotions, social interaction, sexual life). Disability and
      overall psychopathology levels were assessed through the TSD-OC test (SIO test
      for obesity correlated disabilities) and the SCL-90 (Symptom Checklist-90)
      questionnaire, respectively. To verify the validity of the Italian version, the
      analysis of internal consistency, test-retest reliability, and construct validity
      were performed. RESULTS: The observed proportion of agreement concordance of
      results was 50.2% with Cohen's K = 0.336 (CI 95%: 0.267-0.404), indicating a fair
      agreement between the two tests. Test-retest correlation was statistically
      significant (rho = 0.82; p < 0.01); validity (standardized Chronbach's alpha) was
      considered reliable (alpha > 0.70). The analysis of construct validity showed a
      statistically significant association in terms of both total score (rho = -0.66)
      and scores at each single domain (p < 0.01). A high correlation (p < 0.01) was
      observed between Laval questionnaire total and single domain scores and other
      related measures (Body Mass Index, TSD-OC scores, SCL-90 global severity index),
      revealing a high construct validity of the test. CONCLUSIONS: The Italian version
      of the Laval Questionnaire is a valid and reliable measure to assess the health
      related quality of life in subjects with obesity.

PMID- 28506321
TI  - Work Dissatisfaction and Sleep Problems among Canadians in the Latter Half of
      Life.
AB  - This study examined the relationship between work dissatisfaction and sleep
      problems among Canadian adults in the latter half of life, as well as how gender
      and social contact moderate this relationship. Data were obtained from the
      Canadian General Social Survey, Cycle 21 (2007), which sampled adults aged 45 and
      older in 2007. Analyses focused on individuals with employment as their main
      activity. Analyses show that work dissatisfaction positively predicts trouble
      sleeping. There are no significant gender differences in this relationship.
      Social contact with friends buffers this relationship, but social contact with
      family does not, and buffering does not vary significantly between men and women.
      This research contributes to knowledge on sleep problems by showing that work
      dissatisfaction is adversely associated with sleep problems among Canadians in
      the latter half of life, but social contact with friends can weaken this
      deleterious relationship.

PMID- 28506320
TI  - Costs associated with failure to respond to treatment among patients with
      rheumatoid arthritis initiating TNFi therapy: a retrospective claims analysis.
AB  - BACKGROUND: Tumor necrosis factor inhibitors (TNFi) are common second-line
      treatments for rheumatoid arthritis (RA). This study was designed to compare the
      real-world clinical and economic outcomes between patients with RA who responded
      to TNFi therapy and those who did not. METHODS: For this retrospective cohort
      analysis we used medical and pharmacy claims from members of 14 large U.S.
      commercial health plans represented in the HealthCore Integrated Research
      Database. Adult patients (aged >=18 years) diagnosed with RA and initiating TNFi
      therapy (index date) between 1 January 2007 and 30 April 2014 were included in
      the study. Treatment response was assessed using a previously developed and
      validated claims-based algorithm. Patients classified as treatment responders in
      the 12 months postindex were matched 1:1 to nonresponders on important baseline
      characteristics, including sex, age, index TNFi agent, and comorbidities. The
      matched cohorts were then compared on their all-cause and RA-related healthcare
      resource use, and costs were assessed from a payer perspective during the first,
      second, and third years postindex using parametric tests, regressions, and a
      nonparametric bootstrap. RESULTS: A total of 7797 patients met the study
      inclusion criteria, among whom 2337 (30%) were classified as treatment
      responders. The responders had significantly lower all-cause hospitalizations,
      emergency department visits, and physical/occupational therapy visits than
      matched nonresponders during the first-year postindex. Mean total all-cause
      medical costs were $5737 higher for matched nonresponders, largely driven by
      outpatient visits and hospitalizations. Mean all-cause pharmacy costs (excluding
      costs of biologics) were $354 higher for matched nonresponders. Mean RA-related
      pharmacy costs (conventional synthetic and biologic drugs), however, were $8579
      higher in the responder cohort, driven by higher adherence to their index TNFi
      agent (p < 0.01 for all comparisons). A similar pattern of cost differentiation
      was observed over years 2 and 3 of follow-up. CONCLUSIONS: In this real-world
      study we found that, compared with matched nonresponders, patients who responded
      to TNFi treatments had lower all-cause medical, pharmacy, and total costs
      (excluding biologics) up to 3 years from initiation of TNFi therapy. These cost
      differences between the two cohorts provide a considerable offset to the cost of
      RA medications and should encourage close monitoring of treatment response to
      minimize disease progression with appropriate therapy choices.

PMID- 28506322
TI  - Transcatheter closure of a membranous ventricular septal defect in a 1.8-kg
      infant using Amplatzer Duct Occluder II additional size device.
AB  - Catheter closure of membranous ventricular septal defects is generally not
      considered feasible in small infants. We report the successful closure of a
      membranous ventricular septal defect in a 1.8-kg infant with bilateral femoral
      artery occlusion using Amplatzer Duct Occluder II additional size device. The
      ventricular septal defect was crossed from the right ventricle, and the device
      was deployed using transthoracic echocardiographic guidance.

PMID- 28506323
TI  - Transcatheter correction of Scimitar syndrome: occlusion of abnormal pulmonary
      venous drainage and vascular supply in an infant.
AB  - Treatment of Scimitar syndrome is usually surgical; however, if there is "dual
      drainage" - that is, one to the inferior caval vein and the other to the left
      atrium - it is possible to successfully treat this anomaly via a less-invasive
      transcatheter approach. We report a case of Scimitar syndrome in a 21-month-old,
      male infant successfully treated with transcatheter embolisation.

PMID- 28506324
TI  - Preposition accuracy on a sentence repetition task in school age Spanish-English
      bilinguals.
AB  - Preposition knowledge is important for academic success. The goal of this project
      was to examine how different variables such as English input and output, Spanish
      preposition score, mother education level, and age of English exposure (AoEE) may
      have played a role in children's preposition knowledge in English. 148 Spanish
      English children between 7;0 and 9;11 produced prepositions in English and
      Spanish on a sentence repetition task from an experimental version of the
      Bilingual English Spanish Assessment Middle Extension (Pena, Bedore, Gutierrez
      Clellen, Iglesias & Goldstein, in development). English input and output
      accounted for most of the variance in English preposition score. The importance
      of language-specific experiences in the development of prepositions is discussed.
      Competition for selection of appropriate prepositions in English and Spanish is
      discussed as potentially influencing low overall preposition scores in English
      and Spanish.

PMID- 28506325
TI  - A proposed analytic framework for determining the impact of an antimicrobial
      resistance intervention.
AB  - Antimicrobial use (AMU) is increasingly threatened by antimicrobial resistance
      (AMR). The FDA is implementing risk mitigation measures promoting prudent AMU in
      food animals. Their evaluation is crucial: the AMU/AMR relationship is complex; a
      suitable framework to analyze interventions is unavailable. Systems science
      analysis, depicting variables and their associations, would help integrate
      mathematics/epidemiology to evaluate the relationship. This would identify
      informative data and models to evaluate interventions. This National Institute
      for Mathematical and Biological Synthesis AMR Working Group's report proposes a
      system framework to address the methodological gap linking livestock AMU and AMR
      in foodborne bacteria. It could evaluate how AMU (and interventions) impact AMR.
      We will evaluate pharmacokinetic/dynamic modeling techniques for projecting AMR
      selection pressure on enteric bacteria. We study two methods to model phenotypic
      AMR changes in bacteria in the food supply and evolutionary genotypic analyses
      determining molecular changes in phenotypic AMR. Systems science analysis
      integrates the methods, showing how resistance in the food supply is explained by
      AMU and concurrent factors influencing the whole system. This process is updated
      with data and techniques to improve prediction and inform improvements for
      AMU/AMR surveillance. Our proposed framework reflects both the AMR system's
      complexity, and desire for simple, reliable conclusions.

PMID- 28506326
TI  - A model to infer the demographic structure evolution of endangered donkey
      populations.
AB  - Stemming from The Worldwide Donkey Breeds Project, an initiative aiming at
      connecting international researchers and entities working with the donkey
      species, molecularly tested pedigree analyses were carried out to study the
      genetic diversity, structure and historical evolution of the Andalusian donkey
      breed since the 1980s to infer a model to study the situation of international
      endangered donkey breeds under the remarkably frequent unknown genetical
      background status behind them. Demographic and genetic variability parameters
      were evaluated using ENDOG (v4.8). Pedigree completeness and generation length
      were quantified for the four gametic pathways. Despite mean inbreeding was low,
      highly inbred animals were present in the pedigree. Average coancestry,
      relatedness, and non-random mating degree trends were computed. The effective
      population size based on individual inbreeding rate was about half when based on
      individual coancestry rate. Nei's distances and equivalent subpopulations number
      indicated differentiated farms in a highly structured population. Although
      genetic diversity loss since the founder generations could be considered small,
      intraherd breeding policies and the excessive contribution of few ancestors to
      the gene pool could lead to narrower pedigree bottlenecks. Long average
      generation intervals could be considered when reducing inbreeding. Wright's
      fixation statistics indicated slight inbreeding between farms. Pedigree
      shallowness suggested applying new breeding strategies to reliably estimate
      descriptive parameters and control the negative effects of inbreeding, which
      could indeed, mean the key to preserve such valuable animal resources avoiding
      the extinction they potentially head towards, making the present model become an
      international referent when assessing endangered donkey populations.

PMID- 28506328
TI  - The effect of dietary faba bean and non-starch polysaccharide degrading enzymes
      on the growth performance and gut physiology of young turkeys.
AB  - The aim of this study was to investigate the effect of dietary replacement of
      soya bean meal (SBM) with faba bean (FB) and a blend of non-starch polysaccharide
      (NSP) degrading enzymes on the gastrointestinal function, growth performance and
      welfare of young turkeys (1 to 56 days of age). An experiment with a 2*2
      factorial design was performed to compare the efficacy of four diets: a SBM-based
      diet and a diet containing FB, with and without enzyme supplementation (C, FB, CE
      and FBE, respectively). In comparison with groups C, higher dry matter content
      and lower viscosity of the small intestinal digesta were noted in groups FB. The
      content of short-chain fatty acids (SCFAs) in the small intestinal digesta was
      higher in groups FB, but SCFA concentrations in the caecal digesta were
      comparable in groups C and FB. In comparison with control groups, similar BW
      gains, higher feed conversion ratio (FCR), higher dry matter content of excreta
      and milder symptoms of footpad dermatitis (FPD) were noted in groups FB. Enzyme
      supplementation increased the concentrations of acetate, butyrate and total
      SCFAs, but it did not increase the SCFA pool in the caecal digesta. The enzymatic
      preparation significantly improved FCR, reduced excreta hydration and the
      severity of FPD in turkeys. It can be concluded that in comparison with the SBM
      based diet, the diet containing 30% of FB enables to achieve comparable BW gains
      accompanied by lower feed efficiency during the first 8 weeks of rearing. Non
      starch polysaccharide-degrading enzymes can be used to improve the nutritional
      value of diets for young turkeys, but more desirable results of enzyme
      supplementation were noted in the SBM-based diet than in the FB-based diet.

PMID- 28506327
TI  - The Seasonal Variability in Surgical Site Infections and the Association With
      Warmer Weather: A Population-Based Investigation.
AB  - OBJECTIVE To determine whether the seasonality of surgical site infections (SSIs)
      can be explained by changes in temperature. DESIGN Retrospective cohort analysis.
      SETTING The National Inpatient Sample database. PATIENTS All hospital discharges
      with a primary diagnosis of SSI from 1998 to 2011 were considered cases.
      Discharges with a primary or secondary diagnoses of specific surgeries commonly
      associated with SSIs from the previous and current month served as our "at risk"
      cohort. METHODS We modeled the national monthly count of SSI cases both
      nationally and stratified by region, sex, age, and type of institution. We used
      data from the National Climatic Data Center to estimate the monthly average
      temperatures for all hospital locations. We modeled the odds of having a primary
      diagnosis of SSI as a function of demographics, payer, location, patient
      severity, admission month, year, and the average temperature in the month of
      admission. RESULTS SSI incidence is highly seasonal, with the highest SSI
      incidence in August and the lowest in January. During the study period, there
      were 26.5% more cases in August than in January (95% CI, 23.3-29.7). Controlling
      for demographic and hospital-level characteristics, the odds of a primary SSI
      admission increased by roughly 2.1% per 2.8 degrees C (5 degrees F) increase in
      the average monthly temperature. Specifically, the highest temperature group,
      >32.2 degrees C (>90 degrees F), was associated with an increase in the odds of
      an SSI admission of 28.9% (95% CI, 20.2-38.3) compared to temperatures <4.4
      degrees C (<40 degrees F). CONCLUSIONS At population level, SSI risk is highly
      seasonal and is associated with warmer weather. Infect Control Hosp Epidemiol
      2017;38:809-816.

PMID- 28506329
TI  - What to do when a patient wants to record a patient-physician interaction in the
      emergency department.
AB  - Recent technological advances allow for instantaneous high quality video and
      audio recordings with the touch of a button. In Canada, patient privacy is highly
      regulated by provincial legislation, although patients themselves have little in
      the way of laws or regulations to observe. Patients taking video recordings of
      their own medical care does not currently fall under any of the provincial
      privacy laws. With no such governance for the general public, patients generally
      have greater freedom to record a patient-physician interaction. Unfortunately,
      there are no official policies from the provincial physician colleges regarding
      how best to proceed in these circumstances. Therefore, the onus is on individual
      hospitals and emergency departments (EDs) to develop their own policy on video
      recordings. A policy should ideally cover possible recording devices, locations,
      staff involved, and mandate that a written consent form be included with the
      patient's chart. While every request should be considered individually,
      physicians should generally not feel compelled to agree to the patient recording
      the clinical encounter. Patients are legally allowed to record a patient
      physician interaction without consent of their physician, because the patient can
      provide the "one-party consent" for the conversation to be recorded. Physicians
      should accept the possibility that they are being recorded at all times and
      should strive to communicate as clearly and effectively as possible. Physicians
      should strive to provide the same level of care that they would even if they were
      not being recorded, and not let it interfere with their clinical decision-making.

PMID- 28506330
TI  - Edwards valve-in-valve implantation in tricuspid position.
AB  - We present two cases of percutaneous Sapien XT valve-in-valve implantation in the
      tricuspid position: a 20-year-old man with severe congenital pulmonary stenosis
      and percutaneous valvuloplasty, who required surgical implantation of two
      protheses, pulmonary and tricuspid, and a 12-year-old boy with CHD and a
      degenerated tricuspid prosthesis. We implanted three Sapien XT valve-in-valves,
      two in the tricuspid position and one in the pulmonic position. Sapien XT valve
      in-valve implantation in the tricuspid position is feasible and can decrease the
      number of surgeries in CHD patients.

PMID- 28506331
TI  - Glucocorticoids for treating paediatric pulmonary hypertension: a novel use for a
      common medication.
AB  - Laboratory investigations have shown the role of inflammation in the pathogenesis
      of pulmonary hypertension and improvement after anti-inflammatory drugs. Despite
      these observations, reports on the use of steroids to treat pulmonary
      hypertension in humans are absent from the literature. In this article, we report
      the use of glucocorticoids in the treatment of two children with pulmonary
      hypertension, demonstrating its potential utility.

PMID- 28506332
TI  - Correspondence analysis to evaluate the transmission of Staphylococcus aureus
      strains in two New York State maximum-security prisons.
AB  - Prisons/jails are thought to amplify the transmission of Staphylococcus aureus
      (SA) particularly methicillin-resistant SA infection and colonisation. Two
      independently pooled cross-sectional samples of detainees being admitted or
      discharged from two New York State maximum-security prisons were used to explore
      this concept. Private interviews of participants were conducted, during which the
      anterior nares and oropharynx were sampled and assessed for SA colonisation. Log
      binomial regression and correspondence analysis (CA) were used to evaluate the
      prevalence of colonisation at entry as compared with discharge. Approximately 51%
      of admitted (N = 404) and 41% of discharged (N = 439) female detainees were
      colonised with SA. Among males, 59% of those admitted (N = 427) and 49% of those
      discharged (N = 393) were colonised. Females had a statistically significant
      higher prevalence (1.26: P = 0.003) whereas males showed no significant
      difference (1.06; P = 0.003) in SA prevalence between entry and discharge. CA
      demonstrated that some strains, such as spa types t571 and t002, might have an
      affinity for certain mucosal sites. Contrary to our hypothesis, the prison
      setting did not amplify SA transmission, and CA proved to be a useful tool in
      describing the population structure of strains according to time and/or mucosal
      site.

PMID- 28506333
TI  - @Home eTherapy Service for People with Common Mental Health Problems: an
      Evaluation.
AB  - BACKGROUND: Ensuring rapid access to psychological interventions is a priority of
      mental health services. The involvement of peer workers to support the delivery
      of more accessible treatment options such as computerized cognitive behaviour
      therapy (CCBT) is recognized. AIMS: To evaluate the implementation of a third
      sector remote CCBT @Home eTherapy service for people experiencing common mental
      health problems supported by individuals with lived experience. METHOD: Supported
      CCBT packages with telephone support were delivered over a 30-month period. Self
      complete measures identifying levels of depression, anxiety and functioning were
      administered at each treatment appointment. RESULTS: Over 2000 people were
      referred to the @Home eTherapy service; two-thirds attended an initial assessment
      and 53.4% of referrals assigned to CCBT completed treatment. Statistically
      significant improvements in anxiety, depression and functioning were found, with
      61.6% of treated clients meeting recovery criteria. CONCLUSIONS: The service
      meets Improving Access to Psychological Therapies (IAPT) key performance targets,
      and is comparable to other IAPT services using CCBT. Evidence for the successful
      implementation of such a service by a third sector organization is provided.

PMID- 28506334
TI  - [MECP2 duplication syndrome: a clinical analysis of three cases and literature
      review].
AB  - MECP2 duplication syndrome (MDS) is a rare pediatric disease and mainly manifests
      as delayed motor development, language loss or delay, recurrent infection, severe
      intellectual disability, epilepsy, autistic symptoms, and early infantile
      hypotonia. In this article, the three children with this disease were all boys.
      Cases 1 and 2 had delayed motor development, and language loss or delay as
      initial manifestations, and case 3 had recurrent infection as initial
      manifestation. Physical examination showed hypotonia and negative pathological
      signs in each case. Case 1 had tonic-clonic seizures and electroencephalography
      showed focal seizures, for which he was given oxcarbazepine, levetiracetam, and
      clonazepam as the antiepileptic treatment to control seizures. Case 3 experienced
      one absence seizure and three head-nodding seizures with normal
      electroencephalographic findings during these seizures, and therefore, he was not
      given antiepileptic treatment. In each case, recurrent infection was improved
      with the increase in age, but there were no significant improvements in language
      or intelligence. Array-based comparative genomic hybridization (aCGH) showed
      MECP2 duplication in X chromosome in each case, and so they were diagnosed with
      MDS. MDS should be considered for children with delayed development complicated
      by recurrent infection and epileptic seizures, and early aCGH helps with the
      diagnosis of this disease.

PMID- 28506335
TI  - [MECP2 gene and MECP2-related diseases].

PMID- 28506336
TI  - [Alpers-Huttenlocher syndrome caused by a novel compound heterozygous mutation of
      POLG gene: a case report].

PMID- 28506337
TI  - [Mitochondrial diseases and epilepsy].

PMID- 28506338
TI  - [Clinical efficacy of compound glycyrrhizin tablets in the treatment of children
      with nonalcoholic fatty liver disease].
AB  - Department of Pediatrics, First Affiliated Hospital of Nanjing Medical
      University, Nanjing 210029, China. zhuchuanlong@jsph.org.cn.

PMID- 28506339
TI  - [Effect of allergic rhinitis on disease condition and treatment in patients with
      juvenile-onset systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the effect of allergic rhinitis (AR) and its
      intervention on disease condition and medications in patients with juvenile-onset
      systemic lupus erythematosus (JSLE). METHODS: The clinical data of 96 children
      diagnosed with JSLE were collected, and according to the presence or absence of
      AR or other allergic diseases, they were divided into AR group (n=44), non-AR
      group (n=20), and non-allergic group (n=32). The children in the AR group were
      randomly administered with or without intervention (n=22 each). All the children
      were given standard JSLE treatment. The systemic lupus erythematosus disease
      active index (SLEDAI) and application of hormones and immunosuppressants were
      compared between groups. RESULTS: The AR and non-AR groups had significantly
      higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of
      types of immunosuppressants used than the non-allergic group before treatment
      (P<0.05), while there were no significant differences between the AR and non-AR
      groups (P>0.05). After one month of treatment, the AR group with intervention had
      significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids
      than the AR group without intervention (P<0.05), while there was no significant
      difference in the application of immunosuppressants between these two groups
      (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had
      significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and
      number of types of immunosuppressants than the AR group without intervention
      (P<0.05). CONCLUSIONS: JSLE combined with allergic diseases such as AR has an
      adverse effect on disease condition and treatment, and the intervention for AR
      helps with the control of JSLE.

PMID- 28506340
TI  - [Endocrine and metabolic features of female children with Prader-Willi syndrome:
      an analysis of 4 cases].
AB  - This article reports the clinical features and endocrine and metabolic features
      of 4 children with Prader-Willi syndrome (PWS). All the patients were female and
      aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity,
      unusual facies, developmental retardation, and intellectual disability. Genetic
      detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region,
      one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient
      had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of
      endocrine and metabolic disorders: 2 patients had short stature, among whom one
      had delayed appearance of secondary sex characteristics and the other one had
      type 2 diabetes; one patient had insulin resistance and no mammary gland
      development; one patient had a body height of P3-P10 and precocious puberty.
      Patients with PWS have various endocrine disorders, so long-term endocrine follow
      up and management is very important.

PMID- 28506341
TI  - [Effect of obesity on pulmonary function in asthmatic children of different age
      groups].
AB  - OBJECTIVE: To study the effect of obesity on pulmonary function in newly
      diagnosed asthmatic children of different age groups. METHODS: Two hundred and
      ninety-four children with newly diagnosed asthma were classified into preschool
      age (<6 years) and school-age (6 to 12.5 years) groups. They were then classified
      into obese, overweight, and normal-weight subgroups based on their body mass
      index (BMI). All the children underwent pulmonary function tests, including large
      airway function tests [forced vital capacity (FVC%) and forced expiratory volume
      in one second (FEV1%)] and small airway function tests [maximal expiratory flow
      at 25% of vital capacity (MEF25%), maximal expiratory flow at 50% of vital
      capacity (MEF50%), and maximal expiratory flow at 75% of vital capacity
      (MEF75%)]. RESULTS: The school-age group showed lower FEV1%, MEF25%, and MEF50%
      than the preschool-age group (P<0.05) after adjustment for sex and BMI. The
      normal-weight children in the school-age group had lower FEV1%, MEF25%, and
      MEF50% compared with their counterparts in the preschool-age group (P<0.05). The
      overweight children in the school-age group showed lower FVC% and MEF50% than
      those in the preschool-age group. However, all the pulmonary function parameters
      showed no significant differences between the obese children in the preschool-age
      and school-age groups. In the preschool-age group, FVC%, FEV1%, and MEF75% of the
      obese children were lower than those of the normal-weight children. In the school
      age group, only FVC% and FEV1% showed differences between the obese and normal
      weight children (P<0.05). CONCLUSIONS: The effect of obesity on the pulmonary
      function varies with age in children with asthma, and the effect is more obvious
      in those of preschool age.

PMID- 28506342
TI  - [Cardiac autonomic nerve function in obese school-age children].
AB  - OBJECTIVE: To analyze the deceleration capacity (DC) of heart rate, acceleration
      capacity (AC) of heart rate, and heat rate variability (HRV) in obese school-age
      children, and to observe the correlations of BMI with DC, AC, and HRV in these
      children. METHODS: A total of 108 obese school-age children were selected,
      including 75 cases of ortholiposis and 33 cases of dyslipidemia. A total of 103
      healthy school-age children were selected as control group. All the subjects
      underwent 24-hour ambulatory electrocardiography. The comparisons of DC, AC, and
      HRV were made between the obese and control groups, as well as between children
      with ortholiposis and dyslipidemia in the obese group. The correlations of BMI
      with DC, AC, and HRV were analyzed in the obese group. RESULTS: The obese group
      showed lower DC, standard deviation of normal-to-normal R-R intervals (SDNN),
      standard deviation of the average normal-to-normal intervals (SDANN), root mean
      square of successive differences (RMSSD), low-frequency power (LF), and high
      frequency power (HF) than the control group. The AC of the obese group was
      significantly higher than that of the control group (P<0.05). In the obese group,
      children with dyslipidemia had significantly lower DC, SDNN, SDANN, RMSSD, LF,
      and HF, but significantly higher AC and BMI, as compared with those with
      ortholiposis (P<0.01). In the obese group, BMI was negatively correlated with DC,
      SDNN, SDANN, RMSSD, and HF (P<0.05), but positively correlated with AC (P<0.05).
      CONCLUSIONS: Obese school-age children have impaired autonomic nerve function,
      presenting with reduced vagal tone, which is particularly prominent in those with
      dyslipidemia. The more obese the children, the lower the vagal tone, which may
      increase the risks of cardiovascular diseases.

PMID- 28506343
TI  - [Current status of research on infantile cholestatic liver disease in China: a
      visualization analysis].
AB  - OBJECTIVE: To investigate the current status of research on infantile cholestatic
      liver disease in China and future research trends. METHODS: A co-word analysis
      was performed in October 2016. Document retrieval and screening were performed in
      the Chinese databases CNKI and Wanfang Data using "cholestasis" and "infant" as
      key words. Excel 2010 was used to establish a co-occurrence matrix of high
      frequency key words, and Ucinet 6.0 and Netdraw were used to develop a visualized
      network of these high-frequency key words. RESULTS: A total of 383 articles were
      included. The co-occurrence analysis showed that "infant" and "cholestasis" were
      the core of research in this field, and "infantile hepatitis syndrome",
      "neonate", "intrahepatic", "biliary atresia", "heredity and metabolism",
      "hepatitis", "cytomegalovirus", "jaundice", and "conjugated bilirubin" were main
      research topics. Most of the other articles focused on "parenteral nutrition",
      "hepatobiliary imaging", "gene mutation", and "liver biopsy". There were
      relatively few articles on surgical diagnostic techniques and treatment for this
      disease. CONCLUSIONS: The research on infantile cholestatic liver disease in
      China focuses on etiology and differential diagnosis, and genetic diagnosis has
      become a hot topic in recent years. The research on treatment should be enhanced,
      and new diagnostic techniques are the research interest in future.

PMID- 28506344
TI  - [Novel PHEX gene mutations in patients with X-linked hypophosphatemic rickets: an
      analysis of 2 cases].
AB  - OBJECTIVE: To investigate PHEX gene mutations in 2 patients with X-linked
      hypophosphatemic rickets (XLH) and their families and to clarify the genetic
      etiology. METHODS: A retrospective analysis was performed for the clinical data
      of two patients with XLH. High-throughput sequencing was used to detect the PHEX
      gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the
      distribution of mutations in families. RESULTS: Both patients had novel mutations
      in the PHEX gene; one patient had a frameshift mutation, c.931dupC, which caused
      early termination of translation and produced the truncated protein
      p.Gln311Profs*13; the other patient had a splice site mutation, IVS14+1G>A, which
      caused the skipping of exon 15 and produced an incomplete amino acid chain. Their
      parents had normal gene phenotypes. CONCLUSIONS: c.931dupC and IVS14+1G>A are two
      novel mutations of the PHEX gene and might be the new pathogenic mutations of
      XLH.

PMID- 28506345
TI  - [Infantile hypophosphatasia caused by a novel compound heterozygous mutation: a
      case report and pedigree analysis].
AB  - This article reported the clinical features of one child with infantile
      hypophosphatasia (HPP) and his pedigree information. The proband was a 5-month
      old boy with multiple skeletal dysplasia (koilosternia, bending deformity of both
      radii, and knock-knee deformity of both knees), feeding difficulty, reduction in
      body weight, developmental delay, recurrent pneumonia and respiratory failure,
      and a significant reduction in blood alkaline phosphatase. Among his parents,
      sister, uncle, and aunt (other family members did not cooperate with us in the
      examination), his parents and aunt had a slight reduction in alkaline phosphatase
      and his aunt had scoliosis; there were no other clinical phenotypes or abnormal
      laboratory testing results. His ALPL gene mutation came from c.228delG mutation
      in his mother and c.407G>A compound heterozygous mutation in his father. His aunt
      carried c.228delG mutation. The c.407G>A mutation had been reported as the
      pathogenic mutation of HPP, and c.228delG mutation was a novel pathogenic
      mutation. Hypophosphatasia is caused by ALPL gene mutation, and ALPL gene
      detection is an effective diagnostic method. This study expands the mutation
      spectrum of ALPL gene and provides a theoretical basis for genetic diagnosis of
      this disease.

PMID- 28506346
TI  - [Role of short-latency somatosensory evoked potential in the diagnosis of chronic
      inflammatory demyelinating polyneuropathy].
AB  - OBJECTIVE: To investigate the role of short-latency somatosensory evoked
      potential (SSEP) in the diagnosis of chronic inflammatory demyelinating
      polyneuropathy (CIDP). METHODS: A total of 48 children with a confirmed or
      suspected CIDP and 40 healthy children were enrolled. Nerve electrophysiological
      examination and/or SSEP examination was performed (the children in the healthy
      control group only underwent SSEP examination). Four-lead electromyography was
      used for nerve electrophysiological examination, including at least 4 motor
      nerves and 2 sensory nerves. N6 (elbow potential), N13 (cervical cord potential),
      and N20 (cortex potential) of the median nerve and N8 (popliteal fossa
      potential), N22 (lumbar cord potential), and P39 (cortex potential) of the tibial
      nerve were observed by SSEP examination. RESULTS: Among the 48 children with
      CIDP, 35 had demyelination in both motor and sensory nerves, 8 had demyelination
      in sensory nerves, and 5 had axonal degeneration. SSEP examination showed that 7
      had conduction abnormality in the trunk of the brachial plexus and/or the
      posterior root and 33 had damage in the lumbosacral plexus and/or the posterior
      root. The 40 children with abnormal findings of SSEP examination included 8
      children with affected sensory nerves and 5 children with secondary axonal
      degeneration who did not meet the electrophysiological diagnostic criteria for
      CIDP. Compared with the healthy control group, the CIDP group had significantly
      prolonged latency periods of N13 and N22 (P<0.05). CONCLUSIONS: SSEP can be used
      for the auxiliary diagnosis of CIDP, especially in CIDP children with affected
      sensory nerves or secondary axonal degeneration.

PMID- 28506347
TI  - [Association between autism spectrum disorder and epilepsy in children].
AB  - OBJECTIVE: To examine the association between autism spectrum disorder (ASD) and
      epilepsy in children. METHODS: A total of 190 children with ASD were enrolled. A
      self-designed questionnaire, Childhood Autism Rating Scale, and Autism Behavior
      Checklist were used to determine the association between ASD and epilepsy.
      RESULTS: Among the 190 children with ASD, 20 (10.5%) had epileptic seizures and
      12 (6.3%) were diagnosed with epilepsy. The rates of abnormal physical
      development and hearing disorders before the age of one year were significantly
      higher in ASD children with epileptic seizures than in those without epileptic
      seizures (P<0.05). The ASD children diagnosed with epilepsy and those receiving
      epilepsy treatment had a significantly increased rate of abnormal physical
      development before the age of one year (P<0.05). The ASD children with epileptic
      seizures had poorer sensory responses and behavioral competencies than those
      without epileptic seizures (P<0.05). Epilepsy treatment have a positive effect on
      behavioral competencies in ASD children (P<0.05). CONCLUSIONS: There is a
      significant association between ASD and epilepsy in children. The possibility of
      the comorbidity between ASD and epilepsy may be assessed according to the status
      of growth and development before the age of one year, sensory responses and
      behavioral competencies, and the presence or absence of epileptic seizures.

PMID- 28506348
TI  - [Influence of home nurture environment on language development and social emotion
      in children with developmental language disorder].
AB  - OBJECTIVE: To investigate the influence of home nurture environment on language
      development and social emotion in children with developmental language disorder
      (DLD). METHODS: The 1-3 Years Child Home Nurture Environment Scale, Gesell
      Developmental Scale, and Infant-Toddler Social and Emotional Assessment Scale
      were used for the evaluation of 125 children with DLD. A total of 130 children
      with normal language development matched for age and sex were enrolled as control
      group. RESULTS: Compared with the control group, the DLD group had a
      significantly higher proportion of children in a bad home nurture environment and
      significantly lower scores of all domains of home nurture environment (P<0.05).
      In children with DLD, the home nurture environment score was positively
      correlated with the level of language development (r=0.536, P<0.01) and the score
      of ability domain in social emotion (r=0.397, P<0.01) and was negatively
      correlated with the scores of the domains of explicit behavior, covert behavior,
      and imbalance in social emotion (r=-0.455, -0.438, and -0.390 respectively,
      P<0.01). Home nurture environment had direct influence on language development in
      children with DLD and affected their language development via the mediating
      effect of social emotion. CONCLUSIONS: Home nurture environment influences
      language development and social emotion in children with DLD, and social emotion
      has a partial mediating effect between home nurture environment and language
      development.

PMID- 28506349
TI  - [Relationship between fever degree and prognosis in children with bacterial
      bloodstream infection].
AB  - OBJECTIVE: To study the relationship between the degree of fever within 48 hours
      of admission and the prognosis in children with bacterial bloodstream infection.
      METHODS: This study retrospectively analyzed the clinical data of all patients
      diagnosed with sepsis who were admitted to the pediatric intensive care unit
      (PICU) of Shengjing Hospital Affiliated to China Medical University between
      September 2008 and September 2016. The children with bacterial bloodstream
      infection were classified into 5 groups according to the maximum temperature
      within 48 hours of admission: <36.5 degrees C group, >=36.5 degrees C group
      (normal control), >=37.5 degrees C group, >=38.5 degrees C group, and >=39.5
      degrees C group. The mortality was compared between the five groups. Results A
      total of 213 children with bacterial bloodstream infection were enrolled,
      consisting of 5 cases in the <36.5 degrees C group, 44 cases in the >=36.5
      degrees C group, 73 cases in the >=37.5 degrees C group, 69 cases in the >=38.5
      degrees C group, and 22 cases in the >=39.5 degrees C group. A total of 48 cases
      died among the 213 patients. A significant difference was observed in the
      mortality between the five groups (P<0.01). The <36.5 degrees C group and >=39.5
      degrees C group had significantly higher mortality than the normal control group.
      However, there were no significant differences in the mortality between the
      >=37.5 degrees C and >=38.5 degrees C groups and the normal control group.
      Conclusions In children with bacterial bloodstream infection, those with a
      maximum temperature below 36.5 degrees C or above 39.5 degrees C within 48 hours
      of admission have a significantly increased mortality.

PMID- 28506350
TI  - [A preliminary study on the disappearance time of influenza virus antigen].
AB  - OBJECTIVE: To investigate the antigen clearance time, time to symptom
      disappearance, and the association between them using immunofluorescence assay
      for dynamic monitoring of influenza virus antigen in children with influenza.
      METHODS: A total of 1 063 children suspected of influenza who visited the Hunan
      People's Hospital from March to April, 2016 were enrolled. The influenza A/B
      virus antigen detection kit (immunofluorescence assay) was used for influenza
      virus antigen detection. The children with positive results were given
      oseltamivir as the antiviral therapy and were asked to re-examine influenza virus
      antigen at 5, 5-7, and 7 days after onset. RESULTS: Of all children suspected of
      influenza, 560 (52.68%) had an influenza virus infection. A total of 215 children
      with influenza virus infection were followed up. The clearance rate of influenza
      virus antigen was 9.8% (21 cases) within 5 days after onset. The cumulative
      clearance rate of influenza virus antigen was 32.1% (69 cases) within 5-7 days,
      and 98.1% (211 cases) within 7-10 days after onset. Among these children, 6
      children (2.8%) achieved the improvement in clinical symptoms within 3 days after
      onset. The cumulative rate of symptom improvement was 84.7% (182 cases) within 3
      5 days after onset, and 100% achieved the improvement after 5 days of onset.
      CONCLUSIONS: The time to improvement in symptoms after treatment is earlier than
      antigen clearance time. Almost all of the children achieve influenza virus
      antigen clearance 7-10 days after onset. Therefore, it is relatively safe for
      children to go back to school within 7-10 days after onset when symptoms
      disappear.

PMID- 28506351
TI  - [Clinical features and magnetic resonance imaging evaluation of encephalopathy in
      high-risk late preterm infants].
AB  - OBJECTIVE: To investigate the risk factors, clinical features, and magnetic
      resonance imaging (MRI) changes of encephalopathy in high-risk late preterm
      infants. METHODS: Head MRI scan was performed for late preterm infants with high
      risk factors for brain injury who were hospitalized between January 2009 and
      December 2014. The risk factors, clinical features, and head MRI features of
      encephalopathy in late preterm infants were analyzed. RESULTS: A total of 1 007
      late preterm infants underwent MRI scan, among whom 313 (31.1%) had imaging
      features in accordance with the features of encephalopathy of prematurity. Of all
      infants, 76.7% had white matter damage. There was no association between the
      development of encephalopathy and gestational age in late preterm infants, but
      the detection rate of encephalopathy gradually increased with the increasing
      birth weight (P<0.05). The logistic regression analysis showed that a history of
      resuscitation was an independent risk factor for encephalopathy of prematurity
      (P<0.01). CONCLUSIONS: Encephalopathy of prematurity is commonly seen in high
      risk late preterm infants, especially white matter damage. A history of
      resuscitation is an independent risk factor for encephalopathy in late preterm
      infants.

PMID- 28506352
TI  - [Effect of breastfeeding versus formula milk feeding on preterm infants in the
      neonatal intensive care unit].
AB  - OBJECTIVE: To investigate the importance of breastfeeding in preterm infants with
      various gestational ages. METHODS: A total of 639 preterm infants with a
      gestational age of 28+3-36+6 weeks were enrolled, and according to the feeding
      pattern, they were divided into exclusive breastfeeding group (n=237) and formula
      milk feeding group (fed with liquid milk for preterm infants; n=402). These two
      feeding patterns were compared in terms of their effects on weight gain,
      laboratory markers including albumin (Alb) and alkaline phosphatase (ALP),
      incidence rate of feeding intolerance, and incidence rates of complications
      including necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP).
      RESULTS: Compared with the formula milk feeding group, the breastfeeding group
      had a significantly faster increase in body weight, a significantly lower
      incidence rate of NEC, a significantly higher ALP level, and a significantly
      lower Alb level in the preterm infants with a gestational age of 28-30 weeks
      (P<0.05); there were no significant differences between the two groups in the
      incidence rates of anemia, ROP, bronchopulmonary dysplasia (BPD), and nosocomial
      infection and length of hospital stay (P>0.05). For the preterm infants with a
      gestational age of 31-33 weeks, the breastfeeding group had a significantly
      faster increase in body weight, a significantly lower incidence rate of feeding
      intolerance, a significantly shorter length of hospital stay, and a significantly
      higher ALP level (P<0.05); there were no significant differences between the two
      groups in the incidence rates of NEC, anemia, ROP, BPD, and nosocomial infection
      and the Alb level (P>0.05). For the preterm infants with a gestational age of 34
      36 weeks, there were no significant differences in these indices between the two
      groups (P>0.05). CONCLUSIONS: Breastfeeding plays an important role in increasing
      body weight, reducing the incidence rates of feeding intolerance and NEC, and
      shortening the length of hospital stay in preterm infants with a gestational age
      of 28-33 weeks.

PMID- 28506353
TI  - [Effect of baicalin on ATPase and LDH and its regulatory effect on the
      AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity
      disorder].
AB  - OBJECTIVE: To study the effect of baicalin on synaptosomal adenosine
      triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect
      on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein
      kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity
      disorder (ADHD). METHODS: A total of 40 SHR rats were randomly divided into five
      groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low
      dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin
      treatment (n=8 each). Eight WKY rats were selected as normal control group.
      Percoll density gradient centrifugation was used to prepare brain synaptosomes
      and an electron microscope was used to observe their structure. Colorimetry was
      used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used
      to measure the content of AC, cAMP, and PKA. RESULTS: Compared with the normal
      control group, the ADHD model group had a significant reduction in the ATPase
      activity, a significant increase in the LDH activity, and significant reductions
      in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group,
      the methylphenidate hydrochloride group and the medium- and high-dose baicalin
      groups had a significant increase in the ATPase activity (P<0.05), a significant
      reduction in the LDH activity (P<0.05), and significant increases in the content
      of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride
      group, the high-dose baicalin group had significantly greater changes in these
      indices (P<0.05). Compared with the low-dose baicalin group, the high-dose
      baicalin group had a significant increase in the ATPase activity (P<0.05); the
      medium- and high-dose baicalin groups had a significant reduction in the LDH
      activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA
      (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin
      group had a significant increase in the ATPase activity (P<0.05). CONCLUSIONS:
      Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase
      and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent,
      and high-dose baicalin has a significantly greater effect than methylphenidate
      hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating
      the AC/cAMP/PKA signaling pathway.

PMID- 28506354
TI  - [Immunoprotective effect of combined pneumococcal endopeptidase O and
      pneumococcal surface adhesin A vaccines against Streptococcus pneumoniae
      infection].
AB  - OBJECTIVE: To investigate the prokaryotic expression of proteins pneumococcal
      endopeptidase O (PepO) and pneumococcal surface adhesin A (PsaA) in Streptococcus
      pneumoniae and their immunoprotective effect as vaccine candidate proteins.
      METHODS: Specific primers of target gene fragments were designed, and then PCR
      amplification was performed to establish recombinant plasmids pET28a(+)-pepO and
      pET28a(+)-psaA, which were transformed into host cells, Escherichia coli BL21 and
      DE3, respectively, to induce expression. Highly purified target proteins PepO and
      PsaA were obtained after purification. Mucosal immunization was performed for
      BALB/c mice and specific antiserum was prepared. ELISA was used to measure the
      antibody titer, and Western blot was used to analyze the specificity of the
      antiserum of target proteins. The mice were randomly divided into negative
      control group, PepO group, PsaA group, and PepO+PsaA combined immunization group,
      with 18 mice in each group. The models of different serotypes of Streptococcus
      pneumoniae infection were established to evaluate the immunoprotective effect of
      target proteins used alone or in combination. RESULTS: The target proteins PepO
      and PsaA were successfully obtained and Western blot demonstrated that the
      antiserum of these proteins had good specificity. There was no significant
      difference in the titers of IgA in saliva and IgG in serum between the PepO group
      and the combined immunization group (P>0.05); however, these two groups had
      significantly higher antibody titers than the PsaA group (P<0.05). The PepO,
      PsaA, and combined immunization groups had significantly higher protection rates
      for mice infected with Streptococcus pneumoniae D39 and CMCC31436 in the nasal
      cavity than the negative control group (P<0.05). The PepO and combined
      immunization groups had a significantly higher protection rate for mice infected
      with Streptococcus pneumoniae D39 than the PsaA group (P<0.05). The results of
      colonization experiment showed that compared with the control group, the PepO,
      PsaA, and combined immunization groups showed a significant reduction in the
      colonization of Streptococcus pneumoniae (CMCC31693 and CMCC31207) in the
      nasopharynx and lung (P<0.05). The combined immunization group showed a better
      effect on reducing the colonization of CMCC31207 in the lung than the PepO and
      PsaA alone groups. CONCLUSIONS: Combined PepO/PsaA vaccines may produce a better
      protective effect by mucosal immunization compared with the vaccine used alone in
      mice. The combined vaccines can effectively reduce the colonization of
      Streptococcus pneumoniae in the nasopharynx and lung. Therefore, such protein
      vaccines may have a great potential for research and development.

PMID- 28506355
TI  - [Effects of adipose-derived stem cells and non-methylated CpG
      oligodeoxynucleotides on peripheral blood CD4+CD25+ regulatory T cells in young
      mice with food allergy].
AB  - OBJECTIVE: To investigate the effects of adipose-derived stem cells (ADSC) and
      non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of
      peripheral blood CD4+CD25+ regulatory T (Treg) cells in young mice with food
      allergy, as well as their immune intervention effects. METHODS: A total of 40
      female BALB/c mice were randomly divided into control group, allergic group, ADSC
      treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse
      model of food allergy was established by intraperitoneal injection and
      intragastric administration of ovalbumin (OVA) for sensitization and challenge.
      The mice in the control group were treated with normal saline at the same dose;
      the mice in the ADSC treatment group were given intraperitoneal injection of ADSC
      (1*106 cells for each mouse) before and after OVA challenge, and those in the CpG
      ODN treatment group were given intraperitoneal injection of non-methylated CpG
      ODN solution (40 MUg for each mouse) at 1 hour before challenge by gavage. The
      allergic symptom scores were determined for each group after model establishment.
      ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to
      measure the percentage of peripheral blood CD4+CD25+ Treg cells. Hematoxylin and
      eosin staining was used for the pathological analysis of the jejunum. RESULTS:
      The allergic group had significantly higher allergic symptom scores and serum
      level of OVA-IgE than the control group (P<0.05). There were no significant
      differences in the allergic symptom score and the serum level of OVA-IgE between
      the ADSC treatment group and the CpG-ODN treatment group (P>0.05), but these two
      groups had significantly lower allergic symptom scores and serum level of OVA-IgE
      than the allergic group and significantly higher allergic symptom scores and
      serum level of OVA-IgE than the control group (P<0.01). The allergic group had a
      significantly lower percentage of peripheral blood CD4+CD25+ Treg cells than the
      control group (P<0.05). The ADSC treatment group and the CpG-ODN treatment group
      had a significantly higher percentage of peripheral blood CD4+CD25+ Treg cells
      than the allergic group (P<0.05); there were no significant differences between
      these two groups or between them and the control group (P>0.05). Pathological
      results showed structural damage and edema in the jejunal villi, a large number
      of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC
      treatment group and the CpG-ODN treatment group had less structural damage and
      edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte
      infiltration. CONCLUSIONS: ADSC and non-methylated CpG-ODN have a certain effect
      in the treatment of food allergy and can increase the percentage of peripheral
      blood CD4+CD25+ Treg cells and reduce the level of OVA-IgE. They may be
      associated with the induction of immune tolerance and these two treatment have
      comparable effects. Detailed mechanisms of action still need further
      investigation.

PMID- 28506357
TI  - [Research advances in the association between maternal intake of methyl donor
      nutrients during pregnancy and DNA methylation in offspring].
AB  - Maternal nutrition during pregnancy plays a vital role in the health of the
      offspring. Methyl donor nutrients, including folate, vitamin B12, choline,
      betaine, and methionine, directly affect DNA methylation and are closely
      associated with the health of the offspring. As an important part of epigenetics,
      DNA methylation plays an important role in the maintenance of normal cellular
      function, gene expression regulation, and embryonic development. Recent studies
      have shown that maternal nutrition may have a long-lasting effect on the health
      of the offspring via the changes in genomic DNA and/or methylation level in the
      promoter region in specific genes. Therefore, this review article focuses on the
      effect of maternal intake of methyl donor nutrients during pregnancy on DNA
      methylation, in order to explore the effect of the changed methylation status on
      the health of the offspring at the molecular level.

PMID- 28506356
TI  - [Research advances in nutritional assessment methods in children with chronic
      liver diseases].
AB  - Malnutrition is commonly seen in children with chronic liver diseases, and there
      are interactions between them. Chronic liver diseases can cause malnutrition and
      this can affect the prognosis of children with chronic liver diseases. Due to the
      complexity of nutritional assessment in children with chronic liver diseases,
      there are still no unified standards for the diagnosis of malnutrition. Early
      identification of malnutrition and related intervention helps to improve the
      prognosis of children with chronic liver diseases. This article reviews the
      features of nutrition in children with chronic liver diseases and related
      nutritional assessment methods.

PMID- 28506358
TI  - [Research advances in noninvasive high-frequency oscillatory ventilation in
      neonates].
AB  - Noninvasive ventilation is an important respiratory management technique for the
      treatment of mild or moderate respiratory failure in the neonatal intensive care
      unit. Its reasonable application can effectively avoid the use of invasive
      ventilation and related complications. Recent studies have found that noninvasive
      high-frequency oscillatory ventilation has the advantages of both nasal
      continuous positive airway pressure and high-frequency ventilation and can
      rapidly improve oxygenation, effectively remove carbon dioxide, and improve
      respiratory failure. Therefore, it is considered a new and effective noninvasive
      ventilation mode. There are many studies on the rational use, efficacy, and
      safety of noninvasive high-frequency oscillatory ventilation in neonates around
      the world. This article reviews the advances in the clinical studies on
      noninvasive high-frequency oscillatory ventilation in neonates.

PMID- 28506359
TI  - Humans treat unreliable filled-in percepts as more real than veridical ones.
AB  - Humans often evaluate sensory signals according to their reliability for optimal
      decision-making. However, how do we evaluate percepts generated in the absence of
      direct input that are, therefore, completely unreliable? Here, we utilize the
      phenomenon of filling-in occurring at the physiological blind-spots to compare
      partially inferred and veridical percepts. Subjects chose between stimuli that
      elicit filling-in, and perceptually equivalent ones presented outside the blind
      spots, looking for a Gabor stimulus without a small orthogonal inset. In
      ambiguous conditions, when the stimuli were physically identical and the inset
      was absent in both, subjects behaved opposite to optimal, preferring the blind
      spot stimulus as the better example of a collinear stimulus, even though no
      relevant veridical information was available. Thus, a percept that is partially
      inferred is paradoxically considered more reliable than a percept based on
      external input. In other words: Humans treat filled-in inferred percepts as more
      real than veridical ones.

PMID- 28506361
TI  - IgG4-related Disease and the Liver.
AB  - Pathologists are likely to encounter IgG4-related disease in several organ
      systems. This article focuses on helping pathologists diagnose IgG4-related
      disease in the hepatobiliary system. Missing the diagnosis can result in
      unnecessary organ damage and/or unnecessary surgical and cancer therapy. In the
      liver, tumefactive lesion(s) involving the bile ducts with storiform fibrosis and
      an IgG4-enriched lymphoplasmacytic infiltrate are highly concerning for IgG4
      related disease. The recent identification of oligoclonal populations of T cells
      and B cells in IgG4-related disease may lead to molecular tests, new
      therapeutics, and a greater mechanistic understanding of the disease.

PMID- 28506362
TI  - Current Concepts in Pediatric Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disease. Its
      increasing prevalence is a direct result of historically high rates of obesity.
      Hepatocyte lipid accumulation is the first step in a cascade of metabolic and
      inflammatory events thought to precipitate NAFLD. Histologic findings provide
      insight into these events. Lifestyle modification remains the primary therapy in
      children. Current recommendations include vitamin E treatment in those with
      biopsy-proven NASH. Trials of novel drugs are ongoing in adults. As
      efficacy/safety are established, these therapies may be tenable for use in
      children. At the current time, biopsy-driven histology endpoints are necessary to
      establish whether future therapies can improve pediatric or adult-type NASH in
      children.

PMID- 28506363
TI  - Contemporary Evaluation of the Pediatric Liver Biopsy.
AB  - Liver disease in the neonate, infant, child, and adolescent may manifest
      differently depending on the type of disorder. These disorders show marked
      overlap clinically and on light microscopy. Histology and ultrastructural
      examination are used in tandem for the diagnosis of most disorders. A final
      diagnosis or interpretation of the pediatric liver biopsy depends on appropriate
      and adequate clinical history, laboratory test results, biochemical assays, and
      molecular analyses, as indicated by the light microscopic and ultrastructural
      examination.

PMID- 28506360
TI  - Plasmodium P36 determines host cell receptor usage during sporozoite invasion.
AB  - Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite,
      first infect the liver for an initial round of replication before the emergence
      of pathogenic blood stages. Sporozoites represent attractive targets for
      antimalarial preventive strategies, yet the mechanisms of parasite entry into
      hepatocytes remain poorly understood. Here we show that the two main species
      causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on
      two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR
      BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil
      redundant functions during infection by the rodent parasite P. berghei. Genetic
      analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a
      major parasite determinant of host cell receptor usage. Our data provide
      molecular insights into the invasion pathways used by different malaria parasites
      to infect hepatocytes, and establish a functional link between a sporozoite
      putative ligand and host cell receptors.

PMID- 28506364
TI  - Hepatocellular Adenomas: Morphology and Genomics.
AB  - Hepatocellular adenomas (HCAs) are rare benign tumors. This single entity has
      been split into 3 subtypes corresponding to specific mutations: HNF1alpha
      inactivated HCA; inflammatory HCA related to different mutations, all leading to
      activation of STAT3 pathway; and beta-catenin-activated HCA related to CTNNB1
      mutations. The risk of malignant transformation depends on the level of beta
      catenin activation, reported mainly for exon 3, including S45. It is possible
      using specific immunohistochemical markers to identify the 3 different HCA
      subtypes and the level of beta-catenin activation. Fewer than 10% of HCAs remain
      unclassified.

PMID- 28506366
TI  - Antibody-Mediated Rejection After Liver Transplant.
AB  - Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy
      compared with its allograft cohorts of the kidney and lung. Acute AMR is
      diagnosed based on specific clinical and histopathologic criteria: serum donor
      specific antibodies, C4d staining, histopathologic findings on liver biopsy, and
      exclusion of other entities. In contrast, the histologic features of chronic AMR
      are not as specific and it is a more challenging diagnosis to make. Treatments of
      acute and chronic AMR include some combination of steroids, immune-modulating
      agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors.

PMID- 28506365
TI  - Drug-induced Liver Injury: The Hepatic Pathologist's Approach.
AB  - The evaluation of liver biopsies in suspected drug-induced liver injury (DILI)
      can be complex. The biopsy may be approached systematically, by identification of
      histologic lesions and then identification of the overall pattern of injury.
      Potential DILI must be separated from concomitant non-DILI liver disease. The
      findings can be analyzed with respect to the various prescription and
      nonprescription medications and dietary supplements under suspicion to provide a
      complete interpretation of the findings. The pathologic findings, the histologic
      differential diagnosis, and expert interpretation are part of a complete biopsy
      assessment and provide information that is of greatest value in patient
      management.

PMID- 28506367
TI  - Immunohistochemistry in the Diagnosis of Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) can be difficult to distinguish from its mimics,
      including metastatic tumor, benign hepatocellular lesion, and high-grade
      dysplastic nodule, especially when limited biopsy material is available. Hence,
      the judicious use of immunohistochemical stains is necessary to establish a
      correct diagnosis. This article describes advantages and disadvantages of
      immunohistochemical markers that are most commonly used to distinguish between
      these lesions. Diagnostic workup of malignant liver mass (HCC and its histologic
      variants vs metastatic tumor) as well as well-differentiated hepatocellular
      lesion (well-differentiated HCC vs focal nodular hyperplasia vs hepatocellular
      adenoma) is also discussed.

PMID- 28506368
TI  - Human Immunodeficiency Virus Infection, Antiretroviral Therapy, and Liver
      Pathology.
AB  - The improvement in antiretroviral therapy has significantly impacted the lives of
      people living with human immunodeficiency virus (HIV). In high-income countries,
      HIV deaths are predominated by liver disease consequent to viral hepatitis
      coinfection, alcohol, and nonalcoholic fatty liver disease. Published liver
      pathology findings have shifted from being predominated by opportunistic
      infections to the metabolic effects of HIV and antiretroviral therapy as well as
      drug-induced liver injuries. Differences remain between high-income and low
      income countries, where opportunistic infections and immune reconstitution
      syndromes, dominate findings.

PMID- 28506369
TI  - Autoimmune Hepatitis Overlap Syndromes and Liver Pathology.
AB  - Autoimmune hepatitis (AIH) may have an atypical serum alkaline phosphatase
      elevation, antimitochondrial antibodies, histologic features of bile duct
      injury/loss, or cholangiographic findings of focal biliary strictures and
      dilations. These manifestations characterize the overlap syndromes. Patients can
      be classified as having AIH with features of primary biliary cholangitis, primary
      sclerosing cholangitis, or a cholestatic syndrome. The gold standard of diagnosis
      is clinical judgment. Histologic evaluation is a major diagnostic component.
      Treatment is based on algorithms; outcomes vary depending on the predominant
      disease component. Combination therapy has been the principal recommendation.

PMID- 28506370
TI  - Morphologic Subtypes of Hepatocellular Carcinoma.
AB  - Hepatocellular carcinomas can be further divided into distinct subtypes that
      provide important clinical information and biological insights. These subtypes
      are distinct from growth patterns and are on based on morphologic and molecular
      findings. There are 12 reasonably well-defined subtypes as well as 6 provisional
      subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes
      are discussed, with an emphasis on their definitions and the key morphologic
      findings.

PMID- 28506371
TI  - Hepatitis E Virus and the Liver: Clinical Settings and Liver Pathology.
AB  - Infection with hepatitis E virus (HEV) is a leading cause of acute hepatitis
      worldwide, now increasingly recognized also in nonendemic regions. Clinical
      manifestation of hepatitis E includes mostly asymptomatic/subclinical
      presentations or acute, self-limiting hepatitis, but also potentially fatal liver
      failure or chronic hepatitis in immunocompromised individuals. Accordingly,
      hepatitis E histolpathologic patterns range from an unremarkable histology over
      acute (cholestatic) hepatitis with variable degree of necrosis to chronic
      hepatitis with fibrosis. Awareness of hepatitis E and its differential diagnoses,
      knowledge of its clinico-pathologic manifestations and familiarity with its
      diagnostic tools will enable clinicians and pathologists to competently make this
      diagnosis.

PMID- 28506372
TI  - Hepatic Progenitor Cells: An Update.
AB  - Liver regeneration is a fascinating and complex process with many medical
      implications. An important component of this regenerative process is the hepatic
      progenitor cell (HPC). These appealing cells are able to participate in the
      renewal of hepatocytes and cholangiocytes when the normal homeostatic
      regeneration is exhausted. Moreover, the HPC niche is of vital importance toward
      the activation, differentiation, and proliferation of the HPC. This niche
      provides a rich microenvironment for the regulation of the HPC, thanks to the
      intercellular secretion of molecules. New findings indicate that the regenerative
      possibilities in the liver could provide a diverse basis for therapeutic targets.

PMID- 28506373
TI  - Heart Disease and the Liver: Pathologic Evaluation.
AB  - Liver injury due to acute and chronic heart failure has long been recognized.
      This article discusses the concepts of acute cardiogenic liver injury (ACLI) and
      cardiac or congestive hepatopathy (CH) along with their clinical manifestations
      and sequelae. Histologically, ACLI manifests as centrilobular hepatocellular
      necrosis, whereas CH is associated with centrilobular hepatocyte atrophy, dilated
      sinusoids, and perisinusoidal fibrosis, progressing to bridging fibrosis and
      ultimately cirrhosis. ACLI is associated with marked increases in
      aminotransferase levels, whereas CH is associated with a cholestatic pattern of
      laboratory tests. Certain cardiac medications have also been implicated as a
      cause of liver fibrosis.

PMID- 28506374
TI  - Liver Pathology.

PMID- 28506375
TI  - Erratum.

PMID- 28506376
TI  - Community-based pharmacy residents: Engaged at the intersection of health and
      medication needs.

PMID- 28506377
TI  - Beyond the PGY-1 community pharmacy residency: Characterizing career pathways of
      residency graduates.
AB  - OBJECTIVE: To characterize positions obtained upon graduation from Community
      Pharmacy Residency Programs (CPRPs). DESIGN: Descriptive nonexperimental study;
      online cross-sectional survey. SETTING: United States, February to April 2016.
      PARTICIPANTS: One hundred thirty-three community pharmacy residency program
      alumni. INTERVENTION: CPRP alumni identified by past program directors were
      surveyed using 3 contact attempts. MAIN OUTCOME MEASURES: Descriptive measures of
      demographics and information regarding post-CPRP employment including sex,
      region, degree status, number of positions offered, and further specialization
      were determined. Skills developed during CPRPs, such as research, teaching,
      management, advocacy, and clinical service provision during employment, were
      reported. RESULTS: E-mails were sent to 216 potential participants, and 133
      useable survey responses were gathered from CPRP alumni. When asked how many
      positions were offered upon residency graduation, 57% were offered 2 positions
      and 26% were offered 3 positions. Of those employed, 50% of respondents indicated
      employment at the practice site at which they completed their CPRP. The amount of
      time spent on traditional dispensing decreased from the initial post-residency
      position to the current position. The time CPRP graduates spent in roles
      involving research, management, and advocacy activities in their current position
      was increased. CONCLUSION: Graduates of CPRPs spend approximately 34% of their
      time dispensing, which is less than the national average reported by the National
      Pharmacist Workforce Survey. A contributing factor to the expansion of CPRPs
      largely depends on the ability of employment opportunities that embrace the value
      this unique skill set brings. CPRPs foster clinical innovation and leadership in
      the community setting, thus creating additional opportunities for pharmacists to
      demonstrate their value to the health care system.

PMID- 28506378
TI  - Pharmacist-to-prescriber intervention to close therapeutic gaps for statin use in
      patients with diabetes: A randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of a community pharmacist-led intervention on the
      proportion of patients with diabetes placed on statin therapy. DESIGN: The
      Pharmacy Quality Alliance endorsed a performance measure, Statin Use in Persons
      with Diabetes, which evaluates the percentage of patients aged 40-75 years who
      were dispensed a medication for diabetes and also received a statin medication.
      SETTING: This new measure has been implemented within the Electronic Quality
      Improvement Platform for Plans and Pharmacies (EQuIPP) dashboard. PARTICIPANTS:
      In this randomized controlled study, eligible patients identified in EQuIPP are
      those who received medications from a large chain community pharmacy in North
      Carolina, are 40-75 years, had >=2 prescription fills of a diabetes medication,
      and were not receiving statin therapy. INTERVENTION: The control group received
      no intervention. Primary care prescribers of patients in the intervention group
      were contacted by phone and fax to obtain a prescription for an appropriate
      statin. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients
      in each group who were dispensed a statin, calculated using Fisher exact test.
      Sub-analyses were performed to control for patient age, sex, and insurance type.
      RESULTS: The number of statins prescribed was statistically significant between
      intervention group (n = 221) versus control group (n = 199) with 46 statins
      versus 17 statins, respectively (P <0.001). The number of statins dispensed was
      also statistically significant between groups with 34 statins in the intervention
      group versus 15 statins in the control group (P = 0.015). The fourth most common
      (9.2%) reason prescribers rejected statin therapy initiation was "Patient has
      normal cholesterol" and this caused the greatest amount of discussion between
      pharmacist and prescriber. CONCLUSION: Through a brief pharmacist-to-provider
      intervention, a significant gap closure in statin therapy was seen in patients
      with diabetes. There is an opportunity for pharmacies, health plans, and
      prescribers to utilize the community pharmacist in achieving quality, evidence
      based patient care.

PMID- 28506379
TI  - Pharmacist-initiated hepatitis C virus screening in a community pharmacy to
      increase awareness and link to care at the medical center.
AB  - OBJECTIVE: To describe the design and implementation of a pharmacist-led
      hepatitis C virus (HCV) screening and education program in a community pharmacy
      with a protocol for linkage to care at the affiliated hepatology clinic for
      patients born between 1945 and 1965. SETTING: Outpatient pharmacy affiliated with
      the University of Illinois Hospital and Health Sciences System. PRACTICE
      DESCRIPTION: The community pharmacist resident conducted the HCV screening at the
      health system-based community pharmacy. PRACTICE INNOVATION: Community
      pharmacists provided patients with HCV screening and education while patients
      waited for their prescriptions to be ready or upon appointment. Patients were
      given a questionnaire before and after HCV education to assess the impact of
      pharmacist-provided education on patient knowledge. A protocol was developed to
      link patients with a positive HCV antibody test result to care with a
      hepatologist for confirmatory testing at a follow-up appointment at the medical
      center. EVALUATION: Investigators assessed the feasibility of providing the
      screening and education, recorded the number of patients screened, and recorded
      the differences in the questionnaire responses before and after education.
      RESULTS: Pharmacist-led HCV screening services were implemented successfully at
      the community pharmacy. All patients had a negative antibody result; therefore,
      linkage to care at the medical center, although available, was not necessary. The
      self-reported posttest HCV knowledge scores were significantly higher than
      pretest scores. CONCLUSION: This article outlines the methodology for providing a
      multidisciplinary HCV screening, education, and referral program in a community
      pharmacy affiliated with a medical center. Pharmacist-initiated HCV screening in
      a community pharmacy can assist with identifying patients at risk for HCV
      infection and provide patients with linkage to care in the health system. This
      report may encourage community pharmacists to conduct future prospective trials
      to evaluate clinical and economic outcomes of community-based HCV screenings.

PMID- 28506380
TI  - Use of communication tool within electronic medical record to improve primary
      nonadherence.
AB  - OBJECTIVES: The primary objective of this study was to determine if an online
      reminder decreased the rate of primary nonadherence for antihypertensive
      medications in patients seen in 2 primary care clinics in Omaha, NE. The
      secondary objectives were to determine if patients receiving the intervention
      achieved lower blood pressure values at follow-up visits and to determine if the
      intervention decreased the number of days between prescribing and prescription
      pick-up. METHODS: A report was generated in an electronic health record to
      identify patients prescribed a new antihypertensive medication from a physician
      at one of the primary care clinics. Patients that failed to pick up this new
      prescription from the pharmacy within 7 days were sent an electronic reminder via
      an online patient portal. A baseline comparator group was created with the use of
      retrospective chart reviews for the 6 months before prospective data collection.
      Primary nonadherence rate and blood pressure values at follow-up visits were
      compared between the prospective and baseline comparator groups. RESULTS: The
      primary nonadherence rate decreased from 65.5% to 22.2% when comparing the
      baseline and prospective groups, respectively. The mean days to prescription pick
      up decreased from 24.5 to 12.56 in the baseline and prospective groups. The
      prospective group showed a larger decrease in systolic blood pressure (17.33 mm
      Hg vs. 0.75 mm Hg) and diastolic blood pressure (6.56 mm Hg vs. 2.25 mm Hg)
      compared with the baseline group. CONCLUSION: An online reminder through the
      electronic medical record appears to improve patient primary nonadherence, number
      of days between prescribing and prescription pick-up, and blood pressure
      measurements at follow-up visits. This research shows that an online reminder may
      be a valuable tool to improve patient primary adherence and health outcomes.
      Further research is needed with the use of a larger sample population to support
      any hypotheses about the effectiveness of the intervention.

PMID- 28506382
TI  - A simplified pathway to proprotein convertase subtilisin/kexin type 9 inhibitor
      prior authorization approval: A lipid clinic experience.

PMID- 28506383
TI  - Can iPCSK9-induced hypocholesterolemia starve cancer cells?

PMID- 28506381
TI  - Description of drug therapy problem resolution in a statewide care management
      program.
AB  - OBJECTIVE: To describe drug therapy problem (DTP) resolution as part of a
      statewide, team-based care management program. METHODS: This was a retrospective,
      observational study of DTPs documented between March 1 and August 31, 2015. Data
      were retrieved from a Web-based platform 5 months after the observation period.
      DTPs were placed into groups based on the credentials of the person who
      documented the DTP. Next, they were identified as being documented in a
      transitional or nontransitional care setting. DTPs were further classified into 1
      of 3 categories: medication adherence, discrepancy, or optimization. Lastly, DTP
      resolution was assessed. Results were analyzed using descriptive statistics.
      RESULTS: During the 6-month study period, 135,100 DTPs were documented, with 99%
      (n = 133,847) being documented by social work care managers, nurse care managers,
      and pharmacy staff personnel. Pharmacy staff personnel documented the majority of
      DTPs (51.5%), and the majority of DTPs (55%) were identified in the transitional
      care setting. Nurse care managers resolved more discrepancy DTPs (59.3%), whereas
      pharmacy staff personnel resolved more optimization DTPs (47.2%). Social work
      care managers resolved more medication adherence DTPs (68.6%). CONCLUSIONS:
      Pharmacy staff personnel primarily identified and resolved opportunities to
      optimize medication use, whereas nurse care managers primarily identified and
      resolved medication discrepancies. Social work care managers primarily identified
      and resolved problems related to medication adherence. When each member of the
      interdisciplinary care team functioned at the top of their license, all types of
      DTPs were effectively identified and resolved.

PMID- 28506384
TI  - Managing the challenging homozygous familial hypercholesterolemia patient:
      Academic insights and practical approaches for a severe dyslipidemia, a National
      Lipid Association Masters Summit.
AB  - The following article represents material presented and discussed at a symposium
      hosted by the National Lipid Association hosted entitled "Managing the
      Challenging Homozygous Familial Hypercholesterolemia Patient-Academic Insights
      and Practical Approaches for a Severe Dyslipidemia" on November 7, 2015 in
      Orlando, FL. Presenters included G.K.H., A.C.G, and P.M.M. The diagnosis and
      genetic causes of extremely high low-density lipoprotein (LDL) cholesterol, which
      has become known as homozygous familial hypercholesterolemia, were discussed.
      This disorder in adults manifest often by LDL cholesterol in excess of 500 occurs
      in several populations with a prevalence of 1 in 300,000. In more sequestered
      areas, the frequency may be much greater due to founder effects of specific
      settlers carrying the responsible alleles. Although the great majority of these
      patients have a variant sequences in the LDL receptor gene, variants in the
      apolipoprotein B, proprotein convertase subtilisin kexin type 9, or LDL receptor
      adaptor protein gene loci can also be causative. Some individuals have additional
      genetic abnormalities, which have not been fully revealed. In most studies, the
      diagnosis has depended on predefined clinical findings in association with the
      very elevated LDL cholesterol. Standard lipid-lowering drugs such as statins,
      ezetimibe, or bile acid-binding resins are usually only partially beneficial and
      leave the patients at high risk. Lipoprotein apheresis has been a more effective
      therapy and is a mainstay in treatment of many patients. New therapies such as
      mipomersen and lomitapide have reduced LDL dramatically in some but are often
      ineffective in others. Inhibitors of proprotein convertase subtilisin kexin type
      9 can reduce LDL dramatically but in those with null genes for the LDL receptor,
      they are also ineffective. The availability of this battery of drugs has markedly
      improved the potential of pharmacotherapy to control LDL values and prolong the
      life of these patients.

PMID- 28506385
TI  - Hydrophilic vs lipophilic statins in coronary artery disease: A meta-analysis of
      randomized controlled trials.
AB  - INTRODUCTION: Some available experimental studies have reported that hydrophilic
      statins might have advantages compared with lipophilic statins in patients with
      coronary artery disease (CAD). Therefore, we performed a meta-analysis of
      randomized controlled trials (RCTs) investigating the potential differences of
      lipophilic and hydrophilic statins in patients with CAD. METHODS: We
      systematically searched selected electronic databases up to September 2016 to
      select RCTs, which compared clinical outcomes of hydrophilic vs lipophilic
      statins. Primary endpoints were cardiovascular (CV) events: major adverse cardiac
      events, myocardial infarction, cardiac revascularization, stroke, CV death, CV
      hospitalization, and all-cause mortality. Secondary endpoints were safety
      parameters: drug discontinuation, statin-associated muscle symptoms and alanine
      aminotransferase level increase. RESULTS: A total of 11,697 patients from 11
      RCTs, randomly allocated to lipophilic (n = 5736) or hydrophilic statins (n =
      5961), with a mean follow-up 14 months, were included in the meta-analysis. In
      comparison with hydrophilic, the lipophilic statins showed similar risk reduction
      for major adverse cardiac events (relative risk = 0.969, 95% confidence interval
      [CI], 0.835-1.125, P = .682), myocardial infarction (0.880, 95% CI: 0.731-1.058,
      P = .174), CV death (0.757, 95% CI: 0.486-1.180, P = .219), and all-cause
      mortality (0.797, 95% CI: 0.590-1.075, P = .137), as well as cardiac
      revascularization, stroke, drug discontinuation, and statin-associated muscle
      symptoms. CV hospitalization was lower (0.789, 95% CI: 0.643-0.969, P = .024) and
      alanine aminotransferase elevation was higher (2.689, 95% CI: 1.841-3.954, P <=
      .001) in lipophilic than in hydrophilic-treated patients. CONCLUSIONS: In
      conclusion, similarity between hydrophilic and lipophilic statins holds between
      various clinical CAD settings.

PMID- 28506386
TI  - Serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein B, and
      coronary heart disease in a Chinese population undergoing coronary angiography.
AB  - BACKGROUND: Increased serum triglyceride and apolipoprotein B (apoB) levels and
      decreased high-density lipoprotein cholesterol (HDL-C) levels are risk factors
      for cardiovascular diseases. The major types of dyslipidemia in Chinese
      population are hypertriglyceridemia and low HDL-C. OBJECTIVE: This study aimed to
      evaluate the effect of HDL-C, triglyceride, and apoB levels on the risk of
      coronary heart disease (CHD) in a Chinese population undergoing coronary
      angiography. METHODS: This was a cross-sectional study. A total of 1941
      consecutive patients who were referred to coronary angiography for the evaluation
      of suspected CHD were recruited. Lipid parameters were measured after an
      overnight fast. Patients were diagnosed with CHD and without CHD based on the
      findings of the coronary angiography. RESULTS: There were 1363 angiography
      confirmed CHD patients and 578 non-CHD patients. In nonstatin users, the major
      types of dyslipidemia were hypertriglyceridemia combined with low HDL-C, isolated
      low HDL-C, and isolated hypertriglyceridemia, accounting for 21.60%, 19.70%, and
      14.99%, respectively. In statin users, a low to moderate-intensity statin was
      effective in lowering low-density lipoprotein cholesterol (LDL-C). The proportion
      of reaching an LDL-C goal <2.6 mmol/L and <1.8 mmol/L in statin users was 83.20%
      and 55.19%, respectively. In nonstatin users, the triglyceride and apoB levels
      were higher and the HDL-C levels were lower in CHD patients compared with non-CHD
      patients after the adjustment of age, sex, body mass index, diabetes, smoking,
      and alcohol drinking (P = .002, .007, and .005, respectively). After adjusting
      for age, sex, body mass index, diabetes, hypertension, smoking and alcohol
      drinking, the quartiles of triglyceride, HDL-C, and apoB were associated with CHD
      (P for trend = .001, .005, and .003, respectively). CONCLUSION: Serum
      triglyceride, HDL-C, and apoB levels were independently associated with CHD in a
      Chinese population undergoing coronary angiography with a relatively low level of
      LDL-C and a high prevalence of hypertriglyceridemia and low HDL-C.

PMID- 28506387
TI  - Effects of atorvastatin treatment on left ventricular diastolic function in
      peritoneal dialysis patients-The ALEVENT clinical trial.
AB  - BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is common among
      patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory
      biomarkers, such as high-sensitivity C-reactive protein, predict the development
      of LVDD. OBJECTIVES: We hypothesized that PD patients with elevated high
      sensitivity C-reactive protein levels might benefit from statin treatment for
      LVDD and designed a randomized clinical trial to prove the hypothesis. METHODS:
      We screened 213 PD patients and randomly assigned 32 men and women with low
      density lipoprotein cholesterol levels <130 mg/dL, high-sensitivity C-reactive
      protein levels of >=1.5 mg/L, and LVDD, diagnosed by conventional and tissue
      Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg
      daily, or without. The primary end points were changes in TDI diastolic
      parameters or global strain imaging diastolic parameters. RESULTS: Atorvastatin
      reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C
      reactive protein levels by 45% (both P < .001). Follow-up TDI showed significant
      improvement of early mitral flow velocities divided by early diastolic peak
      velocities of the mitral annulus at the medial and lateral site (Nominal change
      for E/Emedial: -5.01 +/- 6.36 vs 1.80 +/- 6.59 for atorvastatin and control,
      respectively, P = .02). There was also a significant improvement in global strain
      imaging after atorvastatin treatment (global strain rate, -17.12 +/- 1.42 vs 
      14.61 +/- 1.78 for atorvastatin and control, respectively, P = .002 and E/SRIVR,
      462.35 +/- 110.54 vs 634.09 +/- 116.81, P = .003). CONCLUSIONS: In this trial of
      PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive
      protein levels and LVDD, atorvastatin significantly improved cardiac diastolic
      function (ClinicalTrials.gov number, NCT01503671).

PMID- 28506389
TI  - Proprotein convertase subtilisin/kexin 9 inhibition in patients with familial
      hypercholesterolemia: Initial clinical experience.
AB  - BACKGROUND: Despite optimal lipid-lowering therapy, a minority of patients with
      familial hypercholesterolemia (FH) reach low-density lipoprotein cholesterol (LDL
      c) target goals. In randomized trials, proprotein convertase subtilisin/kexin 9
      (PCSK9) inhibitors led to impressive LDL-c reductions and a favorable safety
      profile. However, data about the efficacy and safety outside clinical trials are
      not available yet. OBJECTIVE: The purpose of the study is to describe efficacy
      and side effects of PCSK9 inhibitors in FH patients in clinical practice.
      METHODS: Registry of all consecutive FH patients who started with a PCSK9
      inhibitor at a lipid clinic of a university hospital. RESULTS: We analyzed 83 FH
      patients (79 heterozygous FH [heFH]-65 with a genetically confirmed heFH and 14
      with clinical heFH-and 4 homozygous FH [hoFH]), with a mean age of 55.1 +/- 11.6
      years. Treatment with a PCSK9 inhibitor resulted in an additional reduction of
      55% +/- 21% in mean LDL-c levels. Patients with heFH had more LDL-c decrease than
      those with hoFH (56% vs 38%). Patients using ezetimibe monotherapy because of
      statin intolerance (n = 24, 29%) had less LDL-c decrease compared with patients
      who concurrently used statin therapy (47% and 58%, P = .03). Side effects of
      PCSK9 inhibitors were reported by 32 patients (39%). Flu-like symptoms (n = 12)
      and injection site reactions (n = 11) were most frequent. Seven patients (8%)
      discontinued treatment, 5 because of side effects and 2 because of nonresponse.
      CONCLUSION: Our initial experience of PCSK9 inhibition in FH patients in a
      clinical setting showed comparable reduction in LDL-c levels but more side
      effects compared with clinical trials.

PMID- 28506388
TI  - Discordant response of low-density lipoprotein cholesterol and lipoprotein(a)
      levels to monoclonal antibodies targeting proprotein convertase subtilisin/kexin
      type 9.
AB  - BACKGROUND: Clinical trials testing proprotein convertase subtilisin/kexin type 9
      inhibitors (PCSK9i) have demonstrated an unanticipated but significant
      lipoprotein (a) (Lp(a))-lowering effect, on the order of 25% to 30%. Although the
      50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C)
      achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR)
      preservation, the mechanism for Lp(a) lowering is unknown. OBJECTIVE: We sought
      to characterize the degree of concordance between LDL-C and Lp(a) lowering
      because of PCSK9i in a standard of care patient cohort. METHODS: Participants
      were selected from our Center for Preventive Cardiology, an outpatient referral
      center in a tertiary academic medical center. Subjects were included in this
      study if they had (1) at least 1 measurement of LDL-C and Lp(a) before and after
      initiation of the PCSK9i; (2) baseline Lp(a) > 10 mg/dL; and (3) continued
      adherence to PCSK9i therapy. They were excluded if (1) they were undergoing LDL
      apheresis; (2) pre- or post-PCSK9i LDL-C or Lp(a) laboratory values were
      censored; or (3) subjects discontinued other lipid-modifying therapies. In total,
      103 subjects were identified as taking a PCSK9i and 26 met all inclusion and
      exclusion criteria. Concordant response to therapy was defined as an LDL-C
      reduction >35% and an Lp(a) reduction >10%. RESULTS: The cohort consisted of 26
      subjects (15 females, 11 males, mean age 63 +/- 12 years). Baseline mean LDL-C
      and median Lp(a) levels were 167.4 +/- 72 mg/dL and 81 mg/dL (interquartile range
      38-136 mg/dL), respectively. The average percent reductions in LDL-C and Lp(a)
      were 52.8% (47.0-58.6) and 20.2% (12.2-28.1). The correlation between %LDL and
      %Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 (P < .01).
      All subjects except for 1 had a protocol-appropriate LDL-C response to therapy.
      However, only 16 of the 26 (62%; 95% confidence interval 41%-82%) subjects had a
      protocol-concordant Lp(a) response. Although some subjects demonstrated
      negligible Lp(a) reduction associated with PCSK9i, there were some whose Lp(a)
      decreased as much as 60%. CONCLUSIONS: In this standard-of-care setting, we
      demonstrate moderate correlation but large discordance (~40%) in these 2 lipid
      fractions in response to PCSK9i. The results suggest that pathways beyond the
      LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the
      potential to significantly lower Lp(a) in select patients, although confirmation
      in larger multicenter studies is required.

PMID- 28506391
TI  - Lipid profile, changes in laboratory prescriptions are necessary.

PMID- 28506390
TI  - Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and
      the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy
      volunteers.
AB  - BACKGROUND: Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. OM3
      CA is often prescribed concomitantly with a 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitor (statin). OBJECTIVE: The aim of the article was to assess the
      potential for pharmacokinetic interaction between OM3-CA and the statins
      rosuvastatin and simvastatin. METHODS: Data from 2 phase I studies (ECLIPSE III
      and OM-EPA-007 [NCT01486433]) were analyzed. In ECLIPSE III, 59 participants
      received OM3-CA 4 g once daily for 13 days, with rosuvastatin 40 mg (single dose)
      co-administered with the 11th dose. In OM-EPA-007, 52 participants received
      simvastatin 40 mg plus acetylsalicylic acid 81 mg daily for 14 days, with or
      without OM3-CA. Lack of a drug-drug interaction was declared if the 90%
      confidence interval (CI) of the geometric least-squares mean ratio of
      pharmacokinetic parameters was in the range 80% to 125%. RESULTS: For
      rosuvastatin, values for the geometric mean ratio (90% CI) with:without OM3-CA
      were 86.38% (80.68-92.48), 90.50% (85.99-95.25), and 89.01% (84.30-93.98),
      respectively, for maximum plasma concentration (Cmax), area under the
      concentration-time curve up to last measurable concentration (AUC0-t) and
      extrapolated to infinity (AUC0-inf). Co-administration with a single dose of
      rosuvastatin did not affect the multiple-dose pharmacokinetics of constituent OM3
      CA fatty acids eicosapentaenoic acid and docosahexaenoic acid. For simvastatin,
      values for steady state geometric mean ratio (90% CI) with:without OM3-CA were
      91.61% (82.82-101.33) and 87.47% (80.19-95.41), respectively, for Cmax and AUC0
      t. No deaths or serious adverse events occurred in either trial. CONCLUSION: OM3
      CA can be administered with either rosuvastatin or simvastatin without affecting
      the pharmacokinetics of these statins.

PMID- 28506392
TI  - Lipid profile, the world needs to change.

PMID- 28506394
TI  - Iron: Its complicated.

PMID- 28506393
TI  - Partial rescue of neuropathology in the murine model of PKU following
      administration of recombinant phenylalanine ammonia lyase (pegvaliase).
AB  - Pegylated recombinant phenylalanine ammonia lyase (pegvaliase) is an enzyme
      substitution therapy being evaluated for the treatment of phenylketonuria (PKU).
      PKU is characterized by elevated plasma phenylalanine, which is thought to lead
      to a deficiency in monoamine neurotransmitters and ultimately, neurocognitive
      dysfunction. A natural history evaluation in a mouse model of PKU demonstrated a
      profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain
      regions, beginning at 4weeks of age. Following treatment with pegvaliase, the
      number of TH positive neurons was increased in several brain regions compared to
      placebo treated ENU2 mice.

PMID- 28506395
TI  - An enhanced appreciation of cultural competency: Applying knowledge at home and
      abroad.

PMID- 28506396
TI  - An enhanced appreciation of cultural competency: Get off your island!

PMID- 28506397
TI  - An enhanced appreciation of cultural competency: Developing culturally competent
      practitioners.

PMID- 28506398
TI  - Integration of pharmacists into patient-centered medical homes in federally
      qualified health centers in Texas.
AB  - OBJECTIVES: To describe the integration and implementation of pharmacy services
      in patient-centered medical homes (PCMHs) as adopted by federally qualified
      health centers (FQHCs) and compare them with usual care (UC). SETTING: Four FQHCs
      (3 PCMHs, 1 UC) in Austin, TX, that provide care to the underserved populations.
      PRACTICE DESCRIPTION: Pharmacists have worked under a collaborative practice
      agreement with internal medicine physicians since 2005. All 4 FQHCs have
      pharmacists as an integral part of the health care team. Pharmacists have
      prescriptive authority to initiate and adjust diabetes medications. PRACTICE
      INNOVATION: The PCMH FQHCs instituted co-visits, where patients see both the
      physician and the pharmacist on the same day. PCMH pharmacists are routinely
      proactive in collaborating with physicians regarding medication management,
      compared with UC in which pharmacists see patients only when referred by a
      physician. EVALUATION: Four face-to-face, one-on-one semistructured interviews
      were conducted with pharmacists working in 3 PCMH FQHCs and 1 UC FQHC to compare
      the implementation of PCMH with emphasis on 1) structure and workflow, 2)
      pharmacists' roles, and 3) benefits and challenges. RESULTS: On co-visit days,
      the pharmacist may see the patient before or after physician consultation.
      Pharmacists in 2 of the PCMH facilities proactively screen to identify diabetes
      patients who may benefit from pharmacist services, although the UC clinic
      pharmacists see only referred patients. Strengths of the co-visit model include
      more collaboration with physicians and more patient convenience. Payment that
      recognizes the value of PCMH is one PCMH principle that is not fully implemented.
      CONCLUSION: PCMH pharmacists in FQHCs were integrated into the workflow to
      address specific patient needs. Specifically, full-time in-house pharmacists,
      flexible referral criteria, proactive screening, well defined collaborative
      practice agreement, and open scheduling were successful strategies for the
      underserved populations in this study. However, reimbursement plans and provider
      status for pharmacists should be established to sustain this model of care.

PMID- 28506399
TI  - Encouraging pharmacist intervention and standardization of labeling and
      dispensing of oral liquid medications.
AB  - OBJECTIVES: To initiate a call to action for community pharmacists and key
      pharmacy stakeholders in the standardization of oral-liquid dosage forms. DATA
      SOURCES: Not applicable. SUMMARY: Unintentional overdose of medication due to
      administration error results in thousands of pediatric hospitalizations yearly. A
      lack of prescription and dosage device standardization pertaining to oral-liquid
      medications continue to be a public health hazard. Multiple professional
      organizations have publicly endorsed the standardization of oral liquid dosage
      forms. Universal adoption will not be achieved until key-pharmacy stakeholders
      encourage their pharmacists to use best practices when verifying and preparing
      prescription medication. Specifically, these practices should include immediate
      conversion of prescriptions containing non-metric volumes into metric volumes,
      providing appropriate sized oral dosing syringes for all oral liquid
      prescriptions, writing dosing directions in the safest format, and counseling
      patients and caretakers of proper medication administration. CONCLUSION:
      Community pharmacists are uniquely positioned to lead the universal adoption of
      these best practices to ensure proper oral-liquid dosing administration for all
      patients.

PMID- 28506400
TI  - Distraction techniques for immunizations in children and adolescents.

PMID- 28506401
TI  - Plecanatide, Nusinersen, and Obeticholic acid.

PMID- 28506402
TI  - Pharmacists-resource-friendly outcome improvement partners in health care
      delivery.

PMID- 28506403
TI  - An on-road study of sleepiness in split shifts among city bus drivers.
AB  - Bus drivers often work irregular hours or split shifts and their work involves
      high levels of stress. These factors can lead to severe sleepiness and dangerous
      driving. This study examined how split shift working affects sleepiness and
      performance during afternoon driving. An experiment was conducted on a real road
      with a specially equipped regular bus driven by professional bus drivers. The
      study had a within-subject design and involved 18 professional bus drivers (9
      males and 9 females) who drove on two afternoons; one on a day in which they had
      driven early in the morning (split shift situation) and one on a day when they
      had been off duty until the test (afternoon shift situation). The hypothesis
      tested was that split shifts contribute to sleepiness during afternoon, which can
      increase the safety risks. The overall results supported this hypothesis. In
      total, five of the 18 drivers reached levels of severe sleepiness (Karolinska
      Sleepiness Scale >=8) with an average increase in KSS of 1.94 when driving in the
      afternoon after working a morning shift compared with being off duty in the
      morning. This increase corresponded to differences observed between shift workers
      starting and ending a night shift. The Psychomotor Vigilance Task showed
      significantly increased response time with split shift working (afternoon:
      0.337s; split shift 0.347s), as did the EEG-based Karolinska Drowsiness Score
      mean/max. Blink duration also increased, although the difference was not
      significant. One driver fell asleep during the drive. In addition, 12 of the 18
      bus drivers reported that in their daily work they have to fight to stay awake
      while driving at least 2-4 times per month. While there were strong individual
      differences, the study clearly showed that shift-working bus drivers struggle to
      stay awake and thus countermeasures are needed in order to guarantee safe driving
      with split shift schedules.

PMID- 28506404
TI  - [Dural sinus thrombosis following epidural analgesia for delivery: a clinical
      case].
AB  - BACKGROUND AND OBJECTIVES: Neurological complications of spinal anesthesia are
      rare conditions. Headache caused by low pressure of the cerebrospinal fluid is
      one of the most frequent, which occurs after post-dural puncture. A comprehensive
      history and physical exam must be carried out before making the diagnosis of Post
      Dural Puncture Headache (PDPH) and additional tests are necessary to exclude the
      possibility of developing serious neurological complications such as Dural Sinus
      Thrombosis (DST). According to the Case Report a differential diagnosis between
      Dural Sinus Thrombosis with PDPH is discussed. CASE REPORT: A 22 year-old lady,
      ASA Physical Status Class I was admitted at 39 weeks of gestation for delivery.
      For labor pain relief she requested epidural for analgesia, but unfortunately
      accidental dural puncture occurred. She developed an occipital headache and neck
      pain in the second day postpartum which was relieved by both lying down and
      supporting treatment such as rehydration, analgesics and caffeine. On day third
      postpartum she was discharged without complaints. On day fifth postpartum the
      pain returned and became more intense and less responsive to oral analgesics. She
      was admitted to the hospital to do a complete neurological and image
      investigation that showed a lesion consistent with the diagnosis of cortical vein
      thrombosis and Duhral Sinus Thrombosis (TSD). She was treated with oral
      anticoagulants. After two days, a repeated magnetic resonance image (MRI) showed
      partial canalization of the central sinus thrombus. The patient was discharged
      from hospital five days after her admission without any of the initial symptoms.
      CONCLUSION: The report describes a patient who developed severe headache
      following continuous epidural analgesia for delivery. Initially it was diagnosed
      as PDPH, however with the aid of an MRI the diagnosis of TSD was later
      established and treated. TSD is a rare condition and is often underdiagnosed.
      Because of its potentially lethal complications, it should always be considered
      in acute headache differential diagnosis.

PMID- 28506405
TI  - Focus on endocrine surgery.

PMID- 28506406
TI  - Adrenal ganglioneuroma: The Padua Endocrine Surgery Unit experience.
AB  - BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare tumor that originates from the
      gangliar cells of the sympathetic nervous system. It represents less than 5% of
      all adrenal masses. AGN occurs as a large mass, with benign behavior and no
      relevant symptoms and hormonal secretion, but it is often misdiagnosed because
      the preoperative radiological diagnosis is generally challenging. The aim of the
      present paper is to report the experience of a tertiary referral academic center
      regarding the management of AGN and review the relevant literature. METHODS: The
      demographic, diagnostic, surgical, and pathological findings of 666 consecutive
      patients who were adrenalectomized at the Padua Endocrine Surgery Unit between
      1990 and 2015 were retrospectively reviewed in order to focus on AGN. RESULTS:
      The pathology confirmed AGN in 10 patients (1.5% of cases; median age 35 years,
      range 19-73). The diagnosis was incidental and never available before surgery.
      Eight patients were asymptomatic, two presented lower back and abdominal pain.
      The mass was non-secreting in all cases. Preoperative imaging techniques were
      inconclusive about the nature of the mass in all cases. The median size of the
      tumor was 55 mm (range 30-80). The laparoscopic approach was performed in 60% of
      cases. No recurrences occurred after surgery at a median follow-up of 10 years
      (range 1.7-18.2). CONCLUSION: The diagnosis of AGN may be challenging and most
      often occurs after surgery, since it is frequently confirmed by histological
      examination. Radical excision may be achieved by laparoscopic adrenalectomy, with
      a subsequent definitive cure and excellent prognosis at long term follow up.

PMID- 28506407
TI  - Intraoperative neuromonitoring in thyroid surgery: Is the two-staged
      thyroidectomy justified?
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of
      intraoperative neuromonitoring (IONM) in predicting postoperative nerve function
      during thyroid surgery and its consequent ability to assist the surgeon in
      intraoperative decision making. MATERIALS AND METHODS: A total of 2365
      consecutive patients were submitted to thyroidectomy by the same surgical team.
      Group A included 1356 patients (2712 nerves at risk) in whom IONM was utilized,
      and Group B included 1009 patients (2018 nerves at risk) in whom IONM was not
      utilized. RESULTS: In Group A, loss of signal (LOS) was observed in 37 patients;
      there were 29 true positive, 1317 true negative, 8 false positive, and 2 false
      negative cases. Accuracy was 99.3%, positive predictive value was 78.4%, negative
      predictive value was 99.8%, sensitivity was 93.6%, and specificity was 99.4%. A
      total of 29 (2.1%) cases of unilateral paralysis were observed, 23 (1.7%) of
      which were transient and 6 (0.4%) of which were permanent. Bilateral palsy was
      observed in two (0.1%) cases requiring a tracheostomy. In Group A, 31 (2.3%)
      injuries were observed, 25 (1.8%) of which were transient and 6 (0.4%) of which
      were permanent. In Group B, 26 (2.6%) unilateral paralysis cases were observed,
      20 (2%) of which were transient and 6 (0.6%) of which were permanent; bilateral
      palsy was observed in 2 (0.2%) cases. In Group B, 28 (2.8%) injuries were
      observed, 21 (2.1%) of which were transient and 7 (0.7%) of which were permanent.
      Differences between the two groups were not statistically significant.
      CONCLUSIONS: Our results show that IONM has a very high sensitivity and negative
      predictive value, but also good specificity and positive predictive value. For
      these reasons, in selected patients with LOS, the surgical strategy should be
      reconsidered. However, patients need to be informed preoperatively about
      potential strategy changes during the planned bilateral surgery. Future larger
      and multicenter studies are needed to confirm the benefits of this therapeutic
      strategy.

PMID- 28506408
TI  - Genetics of medullary thyroid cancer: An overview.
AB  - : Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is
      sporadic and 25% is the dominant component of the hereditary multiple endocrine
      neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as
      MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or
      absence of hyperparathyroidism, pheocromocytoma and characteristic clinical
      features. Mutations of the RET proto-oncogene are implicated in the pathogenesis
      of MTC, but there are many other mutational patterns involved. In MEN2A, Codon
      634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular
      cysteine-rich domain, is the most commonly altered codon. Many other mutations
      include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs,
      Next-Generation Sequencing (NGS) is taking an increasingly important role. One of
      the most important benefit is the comprehensive analysis of molecular alterations
      in MTC, which allows rapidly to select patients with different risk levels. There
      is a difference in miRNA expression pathway between sporadic and hereditary MTCs.
      Among sporadic cases, expression of miR-127 was significantly lower in those who
      harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are
      associated with many clinical pictures of cancers, such as MEN4. V109G
      polymorphism is associated with sporadic MTCs negative for RET mutations, and
      might influence the clinical course of the patients affected by MTC. Although
      surgery (i.e. total thyroidectomy with neck lymph node dissection) is the
      elective treatment for MTCs, about 80% of patients have distant metastases at
      diagnosis and in this cases surgery is not enough and an additional treatment is
      needed. Interesting results come from two large phase III clinical trials with
      two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib.
      CONCLUSIONS: New genetical testings and therapeutical approaches open new
      perspectives in MTC management.

PMID- 28506409
TI  - The surgical approach to nodule Thyr 3-4 after the 2.2014 NCCN and 2015 ATA
      guidelines.
AB  - BACKGROUND: The incidence of palpables thyroid nodules in general population is
      5% and the prevalence of non -palpable nodules is higher (35-60%) in the endemic
      goiter area. In the last years the new guidelines and new classification related
      to thyroid nodule have changed the indication to treat it. MATERIAL AND METHOD:
      We analyzed the patients treated from January 2013 to June 2016 for Thyr 3 and
      Thyr 4 thyroid nodule sec. Bethesda system. We have divided in I and II period
      related to the 2.2014 and 2015 ATA guidelines and we have evaluated the
      indication to treat, the type of surgical procedure, the incidence of thyroid
      carcinoma and the adverse events. RESULTS: We selected from 909 cases, 252 cases
      surgically treated with preoperative diagnosis of Thyr 3(80 cases) and Thyr 4(172
      cases); carcinoma was found in 21/80 (26.2%) and in 62/172 (26.05%). The period
      was divided from January 2013 to December 2014 and from January 2015 to june 2016
      (first and second period). In II period we found carcinoma in 8/40 Thyr3 and in
      26/88 Thyr 4. The incidence of lobectomy in II period was higher than I period (p
      < 0.0001) sec.guidelines indications. No difference in adverse events. The number
      of cancer is lower in patients treated with lobectomy than those who underwent
      total thyroidectomy (12,5%vs 21,8% in Thyr 3; 15,3% vs 32% in Thyr 4).
      CONCLUSIONS: The indications to treat related to Thyr 3 and Thyr4 are changed in
      the two periods. The number of cancer is lower in patients treated with
      lobectomy. The new guidelines have changed the surgical approach to thyroid
      nodule.

PMID- 28506410
TI  - Effectiveness of Intraoperative Parathyroid Monitoring (ioPTH) in predicting a
      multiglandular or malignant parathyroid disease.
AB  - AIM: The main goal of our study was to confirm the usefulness of intra-operative
      parathyroid hormone (PTH) monitoring (ioPTH) when using minimally invasive
      techniques for treatment of sporadic Primary hyperparathyroidism (pHTP).
      Furthermore, we aimed to evaluate if ioPTH monitoring may help to predict the
      etiology of primary hyperparathyroidism, especially in malignant or
      multiglandular parathyroid disease. METHODS: A retrospective review of 125
      consecutive patients with pHPT who underwent parathyroidectomy between 2001 and
      2016 at the Department of General Surgery was performed. For each patient, the
      specific preoperative work-up consisted of: high-resolution US of the neck by a
      skilled sonographer, sestamibi parathyroid scan, laryngoscopy, and serum
      measurement of PTH, serum calcium levels, and serum 25(OH)D levels. RESULTS: The
      study included 125 consecutive patients who underwent surgery for pHPT. At the
      histological examination, we registered 113 patients with simple adenomatous
      pathology (90,4%), 5 atypical adenomas (4%), 3 cases of parathyroid carcinoma
      (2,4%),, , and 4 histological exams of different nature (3,2%). Overall, 6 cases
      (4,8%) of multiglandular disease were found. We reported 10 cases (8%) of
      recurrent/persistent hyperparathyroidism: 1/10 in a patient affected by atypical
      adenoma, 9/10 in patients with benign pathology. Regarding these 10 cases, in
      three (30%) patients, ioPTH wasn't dosed (only frozen section (FS) exam was
      taken), in 5 cases (50%) ioPTH dropped more than 50% compared to basal value
      (false negative results), and in 2 (20%) cases, ioPTH did not drop >50% from the
      first samples taken, the extemporary exam had confirmed the presence of adenoma
      and the probable second hyperfunctioning adenoma was not found. CONCLUSIONS:
      IoPTH determinations ensure operative success of surgical resection in almost all
      hyperfunctioning tissue; in particular it is very important during minimally
      invasive parathyroidectomy, as it allows avoiding bilateral neck exploration. The
      use of ioPTH monitoring offer increased sensitivity in detecting multiglandular
      disease and can minimize the need and risk associated with recurrent operations,
      and may facilitate cost-effective minimally invasive surgery. Moreover,
      intraoperative PTH monitoring could be a reliable marker to predict a malignant
      disease during parathyroidectomy, showing higher ioPTH baseline value and
      superior drop compared to benign disease.

PMID- 28506411
TI  - Partial thyroidectomy for papillary thyroid microcarcinoma: Is completion total
      thyroidectomy indicated?
AB  - AIM: Papillary thyroid microcarcinoma (PTMC) is increasing in incidence. Despite
      its excellent clinical outcomes, there is still debate regarding which surgical
      approach is more appropriate for PTMC, procedures including hemithyroidectomy
      (HT), total thyroidectomy (TT), and completion thyroidectomy (CT) after initial
      HT and histopathologic examination confirming a PTMC. Here we report our
      experience in the surgical management of PTMC. METHODS: We conducted a
      retrospective evaluation of all patients who received a postoperative diagnosis
      of PTMC between January 2001 and January 2016. Every patient was divided
      according to the type of surgery performed (TT or HT alone). Follow-up consisted
      of regular clinical and neck ultrasonographic examination. Clinical and
      histopathological parameters (e.g. age, sex, lesion size, histological features,
      multifocality, lymph node metastases, BRAF status when available) as well as
      clinical outcomes (e.g. complications rates, recurrence, overall survival) were
      analyzed. RESULTS: Group A consisted of 86 patients who underwent TT, whereas
      Group encompassed 19 patients who underwent HT. Mean follow-up period was 58.5
      months. In Group A, one patient (1.2%) experienced recurrence in cervical lymph
      nodes with need for reoperation. In Group B, eight patients (42%) underwent
      completion thyroidectomy after histopathological examination confirming PTMC,
      while one patient (5.3%) developed PTMC in the contralateral lobe with need for
      reoperation at 2 years after initial surgery. Multifocality was found in 19
      patients in Group A (22%). Of these, 14 presented bilobar involvement, whereas in
      3 cases multifocality involved only one lobe. 1 patient in Group B (5.3%)
      presented with unilateral multifocal PTMC (p = 0.11). CONCLUSIONS: Low-risk
      patients with PTMC may benefit from a more conservative treatment, e.g. HT
      followed by close follow-up. However, appropriate selection of patients based on
      risk stratification is the key to differentiate therapy options and gain better
      results.

PMID- 28506412
TI  - Rationality in prophylactic central neck dissection in clinically node-negative
      (cN0) papillary thyroid carcinoma: Is there anything more to say? A decade
      experience in a single-center.
AB  - AIM: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy.
      Despite its extremely favorable prognosis, cervical lymph node metastases are a
      common feature of PTC and a known independent risk factor for local recurrence.
      However, the role of prophylactic central neck dissection (PCND) remains a matter
      of debate in patients with clinically node-negative (cN0) PTC. To better clarify
      the current role of PCND in the surgical treatment of PTC, evaluating advantages
      and disadvantages of PCND and outcome of cN0 PTC patients who have been treated
      with either total thyroidectomy alone or in combination with PCND. A review of
      recent literature data is performed. METHODS: Between January 2000 and December
      2015, 186 consecutive patients with cN0 PTC were identified to be included in the
      present study. 74 of these underwent total thyroidectomy associated with PCND,
      while 112 patients underwent total thyroidectomy alone. The epidemiological and
      clinical-pathological data of all patients included were collected at diagnosis
      and during follow-up. RESULTS: Overall complication rate was significantly higher
      in the group of patients undergoing PCND (39.2% vs. 17.8%, p = 0.0006). To be
      specific, they presented a considerably increased risk of temporary recurrent
      laryngeal nerve injury (p = 0.009) and of permanent hypothyroidism (p = 0.016).
      Overall survival and recurrence rates did not differ between those undergoing
      PCND and those undergoing total thyroidectomy alone (p = 1.000 and p = 0.715,
      respectively). CONCLUSIONS: The results of the present study do not support the
      routine use of PCND in the treatment of cN0 PTC patients.

PMID- 28506413
TI  - Nasotracheal prolonged safe extubation in acute respiratory failure post
      thyroidectomy: An efficacious technique to avoid tracheotomy? A retrospective
      analysis of a large case series.
AB  - BACKGROUND: Acute respiratory failure is a rare life threatening complication
      following thyroid surgery and its incidence is reported as high as 0.9%. Clinical
      presentation of severe acute respiratory failure is characterized by dyspnea,
      inspiratory airways distress, hypoxia and its standard current management is the
      orotracheal intubation and safe extubation. In case of persistent distress,
      tracheotomy is mandatory. The Authors, analysing a large acute respiratory
      failure clinical series, describe an innovative treatment of this severe
      condition: the nasotracheal prolonged safe extubation. METHODS: Patients treated
      at our Intensive Care Unit for acute respiratory failure following thyroid
      surgery from January 2004 to December 2013, were reviewed. Demographic data
      including gender, age, clinical presentation, laryngoscopic findings, management
      and outcome during a 24-months follow-up after treatment were collected and
      evaluated. Moreover, the strategy for prolonged nasotracheal safe extubation was
      carefully described. RESULTS: Nineteen out of the 2853 patients scheduled for
      thyroid surgery (0.66%) at our University Hospital, developed post-operative
      acute respiratory failure. All of them were treated by nasotracheal prolonged
      safe extubation. The success rate in avoiding highly invasive treatment was of
      84.2%, since only 3 patients needed definitive tracheotomy (15.7%). CONCLUSIONS:
      In our series, the prolonged safe extubation reduced the almost totality of
      expected tracheotomies in patients with acute respiratory failure following
      thyroid surgery (84.2%), demonstrating its feasibility and efficacy. It was a
      well tolerated and minimal invasive procedure that allowed a good respiratory
      ability and a fast clinical resolution of the laryngeal functional impairment.

PMID- 28506414
TI  - Unintentional recurrent laryngeal nerve injuries following thyroidectomy: Is it
      the surgeon who pays the bill?
AB  - BACKGROUND: Thyroidectomy is one of the most common intervention in general
      surgery and, after the turn of the century, its rate has sharply increased, along
      with a worldwide increased incidence of differentiated thyroid cancers.
      Therefore, injuries of the recurrent laryngeal nerve have become one of the most
      frequent cause of surgical malpractice claims, mostly following surgery for
      benign pathology. MAIN BODY: Even if the incidence of definitive paralysis is
      generally lower than 3%, during the last 20 years in Italy, the number of claims
      for damages has sharply raised. As a consequence, a lot of defensive medicine has
      been caused by this issue, and a witch-hunt has been accordingly triggered, so
      determining mostly a painful and lasting frustration for the surgeons, who
      sometimes are compelled to pay a lot of money for increasing insurance premiums
      and lawyers fees. Recurrent laryngeal nerve injury should be considered as a
      potentially catastrophic predictable but not preventable event, rather than the
      result of a surgical mistake. CONCLUSION: Purposes of the Authors are analyzing
      incidence, conditions of risk, and mechanisms of recurrent laryngeal nerve
      injuries, underlining notes of surgical technique and defining medical practice
      recommendations useful to reduce the risk of malpractice lawsuits and judgments
      against surgeons.

PMID- 28506415
TI  - Risk of malignancy in thyroid nodules classified as TIR-3A: What therapy?
AB  - BACKGROUND: The aim of the present study was to assess the clinical applicability
      of the TIR3A category in managing thyroid nodules, to examine the malignancy
      rates of TIR 3A and TIR 3B nodules, and to suggest management guidelines for
      these nodules. MATERIALS AND METHODS: Thyroid cytologies performed in patients
      referred to our Department between January 2014 and August 2016 were classified
      according to the guidelines published by the SIAPEC. 102 cases were included in
      this retrospective study and were divided into two groups: 19 TIR3A were included
      in group A and 83 TIR3B in group B. RESULTS: In group A, malignancy was diagnosed
      in 4 (21.1%) cases, papillary thyroid cancer was found in 3 patients and
      follicular thyroid cancer in 1; one case was classified as microcarcinoma, in two
      cancer was multicentric and bilateral and in one central node metastases were
      observed. In Group B malignancy was diagnosed in 48 (57.8%) patients, papillary
      thyroid cancer was found in 36 patients and follicular cancer in 12;
      microcarcinoma was observed in 25 cases, 12 were unilateral multicentric and 7
      bilateral multicentric; in 3 cases central node metastases were present.
      CONCLUSION: Thyroid nodules with TIR3A cytology have a lower risk of malignancy
      than TIR3B cases, for which the new SIAPEC classification has proved accurate and
      effective. Malignancy rates in nodules with TIR3A cytology are higher than
      expected, although the real and accurate definition of the risk is extremely
      difficult. The recommendation to perform an accurate follow-up and repeat the
      fine-needle aspiration still appears the best option. For better management of
      patients with TIR3A cytology a careful assessment of risk factors and ultrasound
      characteristics is always needed. Further multicenter studies with longer follow
      up are needed to better define the efficacy of this classification, the actual
      cancer risk, and the best management of these lesions.

PMID- 28506416
TI  - Advancement of thyroid surgery video recording: A comparison between two full HD
      head mounted video cameras.
AB  - BACKGROUND: The aim of this study was to test two different video cameras and
      recording systems used in thyroid surgery in our Department. This is meant to be
      an attempt to record the real point of view of the magnified vision of surgeon,
      so as to make the viewer aware of the difference with the naked eye vision.
      MATERIALS AND METHODS: In this retrospective study, we recorded and compared
      twenty thyroidectomies performed using loupes magnification and microsurgical
      technique: ten were recorded with GoPro(r) 4 Session action cam (commercially
      available) and ten with our new prototype of head mounted video camera. RESULTS:
      Settings were selected before surgery for both cameras. The recording time is
      about from 1 to 2 h for GoPro(r) and from 3 to 5 h for our prototype. The average
      time of preparation to fit the camera on the surgeon's head and set the
      functionality is about 5 min for GoPro(r) and 7-8 min for the prototype, mostly
      due to HDMI wiring cable. Videos recorded with the prototype require no further
      editing, which is mandatory for videos recorded with GoPro(r) to highlight the
      surgical details. CONCLUSION: the present study showed that our prototype of
      video camera, compared with GoPro(r) 4 Session, guarantees best results in terms
      of surgical video recording quality, provides to the viewer the exact perspective
      of the microsurgeon and shows accurately his magnified view through the loupes in
      thyroid surgery. These recordings are surgical aids for teaching and education
      and might be a method of self-analysis of surgical technique.

PMID- 28506417
TI  - New perspectives in the diagnosis of thyroid follicular lesions.
AB  - Thyroid nodules are very common, affecting 19%-67% of the adult population.
      However, about 10% of them harbor a malignant lesion. Consequently, the first aim
      in their clinical evaluation is to exclude malignancy. Fine-needle aspiration
      cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid
      nodules. However, FNAC has a main diagnostic limit, namely cellular atypias of
      indeterminate significance, which require surgical excision and histological
      examination to differentiate benign from malignant lesions. Histology reports
      show that approximately 80% of these patients harbor a benign lesion. Therefore,
      in order to reduce unnecessary thyroidectomy, over the last years, the
      cytological classification of thyroid nodules has been revised and a number of
      new instrumental and molecular approaches have been proposed. In the present
      article, we will attempt to summarize the most recent cytological, molecular and
      echographic strategies to enhance the diagnostic accuracy of preoperative thyroid
      follicular lesions. In particular, we will discuss the new cytological
      classifications from the Bethesda System for Reporting Thyroid Cytopathology
      (BSRTC), the British Thyroid Association-Royal College of Pathologists (PTA
      RCPath) and the new Italian Society for Anatomic Pathology and Cytology (SIAPEC
      2014. We will review molecular tests evaluated to ameliorate follicular lesion
      diagnosis as well as the clinical utility of the new echographic Thyroid Imaging
      Reporting and Data System (TI-RADS) score.

PMID- 28506418
TI  - Timing and extension of lymphadenectomy in medullary thyroid carcinoma: A case
      series from a single institution.
AB  - BACKGROUND: Medullary thyroid carcinoma is an aggressive tumor and presents with
      significant morbidity and mortality and a high rate of lymph node metastases. The
      combination of total thyroidectomy and cervical lymphadenectomy is the essential
      treatment for those patients presenting with cervical lymph node metastases.
      MATERIALS AND METHODS: A retrospective analysis of 117 patients operated for
      medullary thyroid carcinoma over a period of 15 years at a single institution.
      Surgical complications and calcitonin levels were noted. RESULTS: Nodal
      metastases were detected in the central compartment in 72.6% patients. Positive
      lymph nodes were detected in the lateral compartment of 34 patients who had
      undergone ipsilateral dissection and in all 10 patients of those with bilateral
      surgery. We found 3 cases of unilateral transient recurrent laryngeal nerve
      palsy, 15 cases of temporary hypoparathyroidism, a permanent accessory nerve
      lesion and a case of chylous fistula. Normalization of post-operative calcitonin
      was found in 82.6% and of patients who underwent total thyroidectomy and central
      neck dissection alone compared to 35.4% in those with ipsilateral and bilateral
      neck dissection. CONCLUSIONS: Total thyroidectomy and cervical lymphadenectomy
      planned on the ultrasound preoperative study and on the calcitonin level
      represent the standard of treatment for medullary thyroid carcinoma.

PMID- 28506419
TI  - Radioguided thyroidectomy for follicular tumors: Multicentric experience.
AB  - BACKGROUND: The diagnosis of thyroid nodular diseases requires an integrated
      approach that has been widely established over the past years. This strategy
      includes: ultrasonography (US) with; implemented Color-Power-Doppler,
      conventional scintigraphy also with positive indicators, specific pathological
      studies targeted by immunohistochemically-assays, and the fine needle; aspiration
      biopsy (FNAB), which, usually, in case of "Follicular Lesions" (10-20%) findings
      is; unable to distinguish carcinoma from follicular adenoma, then indicating the
      necessity of surgery to; obtain a correct diagnosis. The aim of this study was to
      evaluate the role of the scintigraphy with; positive indicators, both
      preoperatively in diagnostic approach of the thyroid nodules and;
      intraoperatively as a guide to the extension of the surgical excision. METHODS:
      On 4482 Thyroidectomy performed, we selected 360 cases of follicular neoplasms
      (192; females and 168 males). In the preoperative phase, these patients underwent
      99 m Tc-sestaMIBI; scintigraphy with both early (10 min) and late (2 h) image
      acquisition, which were later; compared to the ones obtained by image subtraction
      of means 99 m Tc-pertechnetate. Following the; sestamibi administration before
      intervention, we selected the most up-taking nodularity with the; assistance of a
      specific surgical probe (Neoprobe), quantifying uptake with relation to the
      surgical pathology, for an amount of 324 total thyroidectomies and 36 hemi
      thyroidectomies. RESULTS: In all cases of multinodular goiter the benign nodules
      showed an intraoperative low sestamibi uptake whereas follicular carcinomas
      showed both a high preoperative uptake and, as a; percentage, the highest values
      of intraoperative uptake; on the other hand, follicular adenomas had; both pre
      and intraoperative mean values of uptake. On the contrary, papillary carcinomas
      only; showed a mild uptake. CONCLUSIONS: Preoperative sestamibi scintigraphy
      confirmed its importance in improving the information obtained through different
      diagnostic investigations. Also intraoperatively, it pointed; out high-risk
      nodules more accurately. Therefore, radio (Sestamibi) guided surgery could have
      an; interesting rule in the thyroid follicular lesion treatment.

PMID- 28506420
TI  - Update on the role of ultrasound guided radiofrequency ablation for thyroid
      nodule treatment.
AB  - Thyroid nodules can be frequently detected in general population, most of them
      are benign, however malignant cases are rising in the past decades. Ultrasound
      (US) is the most common imaging modality to assess thyroid nodular lesions, plan
      patient work-up and guide minimally invasive treatment. The present review paper
      has been researched to evaluate the current status of radiofrequency ablation
      (RFA) treatment in order to evaluate indications, techniques, complications,
      limitations and outcome assessment in benign solid, partially cystic nodules and
      recurrent malignant nodules. RFA comparison with other ablation techniques has
      been provided as well. US guided Radiofrequency ablation has been proved to be
      effective and safe in cases of benign thyroid nodules and a promising treatment
      method alternative to surgery for patients with recurrent papillary thyroid
      cancer. It's major role lies in significant reduction of thyroid nodule mean
      volume and improvement of the patient symptoms. However, future multicenter
      studies are warranted to better clarify the multi-parametric patient selection
      criteria and evaluate RFA technique efficacy, advantages and limitations in the
      variety of thyroid nodular disease.

PMID- 28506421
TI  - Swallowing disorders after thyroidectomy: What we know and where we are. A
      systematic review.
AB  - INTRODUCTION: Dysphagia and hoarseness are possible complications that can be
      observed in patients undergoing thyroidectomy or other neck surgery procedures.
      These complaints are usually related to superior and inferior laryngeal nerves
      dysfunction, but these can appear even after uncomplicated surgical procedure.
      METHODS: We reviewed the current literature available on MEDLINE database,
      concerning the swallowing disorders appearing after the thyroidectomy. The
      articles included in the review reported pathophysiology and diagnostic concerns.
      RESULTS: Twenty articles were selected for inclusion in the review. Depends on
      the possible causes of the difficulty swallowing (related to nerve damage or
      appearing after uncomplicated thyroidectomy), different types of diagnostic
      procedures could be used to study patient discomfort, as well as intraoperative
      nerve monitoring, fiber optic laryngoscopy, endoscopy, pH monitoring, esophageal
      manometry and videofluorography. Among all these procedures, videofluorography is
      considered the gold standard to evaluate the entire swallowing process, since
      that allows a real-time study of all the three phases of swallowing: oral phase,
      pharyngeal phase and esophageal phase. CONCLUSION: The diagnostic procedures
      described can help to identify the mechanisms involved in swallowing disorders,
      with the aim to choose the best therapeutic option. More studies are needed for
      understanding the causes of the dysphagia appearing after thyroidectomy.

PMID- 28506422
TI  - Epinephrine use and training in schools for food-induced anaphylaxis among non
      nursing staff.

PMID- 28506423
TI  - A case of recurrent facial angioedema associated with elevated tree pollen
      counts.

PMID- 28506424
TI  - Increased risk of systemic reactions extends beyond completion of rush
      immunotherapy.

PMID- 28506425
TI  - Fluoroquinolone resistance in Streptococcus pneumoniae isolates in Germany from
      2004-2005 to 2014-2015.
AB  - Streptococcus pneumoniae is a major cause of bacterial pneumonia, sepsis and
      meningitis worldwide. Prevalence of levofloxacin-resistant S. pneumoniae isolates
      in Germany and associated mutations in the quinolone resistance determining
      regions (QRDRs), as well as serotype distribution and multi locus sequence types
      (MLST) are shown. 21,764 invasive S. pneumoniae isolates from Germany, isolated
      in the epidemiological seasons from 2004/05 to 2014/15 were analyzed at the
      German National Reference Centre for Streptococci (GNRCS) for their levofloxacin
      resistance by micro broth dilution method. All resistant (minimal inhibitory
      concentration (MIC) >=8MUg/ml) and intermediate (MIC >2MUg/ml and <8MUg/ml)
      isolates were selected for the present study. Additionally, 29 susceptible
      isolates were randomly selected. A total of ninety isolates were tested for their
      levofloxacin-MIC by Etest, their serotype and sequence type, as well as for point
      mutations at the QRDRs in the genes parC, parE, gyrA and gyrB. Twenty-five
      isolates exhibited levofloxacin MICs <2MUg/ml (Etest) and no mutations in the
      QRDRs. Four isolates with MICs=2MUg/ml had one mutation in parC; isolates with
      MICs >2MUg/ml all had one or more mutations in the QRDRs. Four of nine
      intermediate isolates had a mutation in either parC or gyrA, and four isolates
      had mutations in both parC and gyrB. One isolate had mutations in both parC and
      gyrA. All isolates with MICs >=8MUg/ml (52) had mutations in both topoisomerase
      IV and gyrase. Serotypes associated with levofloxacin resistance shifted from a
      majority of PCV13 serotypes before the introduction of the PCV13 vaccine towards
      non-PCV serotypes. Resistant isolates were almost exclusively found among adults
      (98.1%).

PMID- 28506426
TI  - Heterogeneity of FHF1 related phenotype: Novel case with early onset severe
      attacks of apnea, partial mitochondrial respiratory chain complex II deficiency,
      neonatal onset seizures without neurodegeneration.
AB  - INTRODUCTION/OBJECTIVES: We report the case of a child prospectively followed in
      our institution for a severe, neonatal onset epilepsy presenting with severe
      attacks of apnea that were not initially recognized as seizure since they were
      not associated with any abnormal movement and since interictal EEG was normal.
      Recording of attacks using prolonged video-EEG recording allowed to confirm the
      diagnosis of epileptic seizures. RESULTS: Using whole exome sequencing we found a
      de novo heterozygous, missense mutation of FHF1 (p.Arg52His, NM_004113), a
      mutation that has been very recently described in 7 patients with an early onset
      epileptic encephalopathy. The initial workup showed a partial deficit of the
      complex II of the respiratory chain in muscle and liver. The prospective follow
      up demonstrated that 2 drugs seemed to be more effective than the others: sodium
      blocker carbamazepine, and serotonin reuptake blocker fluoxetine. GABAergic drugs
      seemed to be ineffective. No drug aggravated the epilepsy. DISCUSSION: This case
      report contributes to the description of an emerging phenotype for this
      condition.

PMID- 28506427
TI  - Italy introduces pre and post operation monitoring phases for offshore seismic
      exploration activities.
AB  - Concern is growing that marine fauna can be affected by noise such as naval
      sonar, pile driving or geophysical surveys, among others. Literature reports a
      variety of animal reactions to human noise (from apparently null or negligible to
      strong). However, conclusive results on its effects on marine mammals at
      individual and population level are still lacking. In 2015, the Italian
      Environmental Impact Assessment Commission mandated seismic operators apply a
      standard scientific protocol comparing marine mammal presence before, during, and
      after offshore seismic survey. For 60days before and after the survey, marine
      mammals are monitored using visual and acoustic methods. One or more acoustic
      autonomous recorders, depending on area size, must also be deployed throughout
      the three phases for continuous monitoring. Consistent data gathered from many
      surveys will enable robust statistical analysis of results. Diffusion of this
      monitoring method internationally would improve the study of far-reaching,
      intense, low frequency noise.

PMID- 28506428
TI  - Polycyclic aromatic hydrocarbons and heavy metals in the Cispata Bay, Colombia: A
      marine tropical ecosystem.
AB  - The concentrations of polycyclic aromatic hydrocarbons and heavy metals were
      evaluated in shallow sediments, water, fish and seabird samples from the Cispata
      Bay, Colombia. The heavy metals concentrations in the sediment was in the
      following order: Cu>Pb>Hg>Cd. The heavy metal concentration was different
      (p<0.05) in juvenile and adult birds. High concentrations of mercury were
      registered in the seabird (10.19+/-4.99mgkg-1) and fish (0.67MUgg-1) samples. The
      total concentration of polycyclic aromatic hydrocarbons ranged from 7.0-41ngg-1
      in sediment, 0.03-0.34ngmL-1 in water samples, 53.24ngg-1 in fish, and 66ngg-1 in
      seabirds. The high concentrations of heavy metals in seabirds may be explained by
      their feeding habits. The presence of polycyclic aromatic hydrocarbons in the
      Cispata Bay may be due to hydrocarbon spills during oil transport at the nearby
      oil port.

PMID- 28506429
TI  - Deteriorating respiratory health in Nepal: a call for action.

PMID- 28506430
TI  - George E. Palade memorial lecture: My life in pancreatic research-unexpected
      results may open the door.
AB  - The Palade Prize is the most distinguished award of the IAP for achievement in
      pancreatic research. It is named after George E. Palade, who in 1974 was awarded
      the Nobel Prize for his work on protein trafficking in pancreatic acinar cells.
      It is a great honor to be awarded the 2016 Palade Prize. While I was in graduate
      school, I was conducting research on hypothalamo-pituitary-thyroid axis; after
      finishing graduate school, I began research on amylase isoenzymes. This was the
      first step of my pancreatic research. Once I discovered that there are close
      relationships among blood glucose levels, amylase activity, and exocrine
      pancreatic function, I continued on to the next challenge. I performed research
      on the relationship between exocrine and endocrine aspects of the pancreas,
      pancreatic exocrine functions in diabetes mellitus, the role of cholecystokinin
      (CCK) and its synthetic analogue on exocrine and endocrine pancreas function, the
      role of CCK on the pathogenesis of pancreatitis, the cellular mechanisms of
      reversible and irreversible pancreatitis, and pancreatic stellate cell
      activation. In addition, I established guidelines for the diagnosis and
      management of acute, chronic and autoimmune pancreatitis as a chief investigator
      of the Research Committee of Intractable Pancreatic Diseases supported by the
      Ministry of Health, Labour and Welfare in Japan.

PMID- 28506431
TI  - Usefulness of three-dimensional magnetic resonance cholangiopancreatography with
      partial maximum intensity projection for diagnosing autoimmune pancreatitis.
AB  - PURPOSE: To compare three-dimensional magnetic resonance cholangiopancreatography
      (MRCP) with/without partial maximum intensity projection (MIP) and endoscopic
      retrograde cholangiopancreatography (ERCP) in patients with autoimmune
      pancreatitis (AIP). MATERIALS AND METHODS: Three-dimensional MRCP and ERCP images
      were retrospectively analyzed in 24 patients with AIP. We evaluated the narrowing
      length of the main pancreatic duct (NR-MPD), multiple skipped MPD narrowing (SK
      MPD), and side branches arising from the narrowed portion of the MPD (SB-MPD)
      using four MRCP datasets: 5 original images (MIP5), 10 original images (MIP10),
      all original images (full-MIP), and a combination of these three datasets (a
      MIP). The images were scored using a 3- or 5-point scale. The scores of the four
      MRCP datasets were statistically analyzed, and the positive rate of each finding
      was compared between MRCP and ERCP. RESULTS: The median scores for SB-MPD on MIP5
      and a-MIP were significantly higher than those on MIP10 and full-MIP. In other
      words, partial MIP is superior to full-MIP for visualization of detailed
      structures. The positive rate for SB-MPD on full-MIP was significantly lower than
      that on ERCP, whereas the positive rate on MIP5, MIP10, and a-MIP was not
      significantly different from that on ERCP. Moreover, the positive rate for NR-MPD
      and SK-MPD on the MRCP images was significantly higher than that on the ERCP
      images. CONCLUSION: Partial MIP is useful for evaluating the MPD and is
      comparable with ERCP for diagnosing AIP.

PMID- 28506432
TI  - The ICUC(r) app: Can it pave the way for quality control and transparency in
      medicine?

PMID- 28506433
TI  - Awareness in the crowd: Beta power and alpha phase of prestimulus oscillations
      predict object discrimination in visual crowding.
AB  - Visual crowding is among the factors that most hamper conscious object
      perception. However, we currently ignore the neural states that predispose to an
      accurate perception within different crowding regimes. Here, we performed single
      trial analyses of the electroencephalographical (EEG) oscillations, evaluating
      the prestimulus power and phase differences between correct and incorrect
      discrimination during a letter-crowding task, where irrelevant letters were
      placed nearby (strong crowding) or far (mid crowding) relative to the target.
      Results show that prestimulus alpha (8-12Hz) power was related to target
      discrimination in the mid, but not in the strong, crowding condition.
      Importantly, accurate discrimination in the strong crowding condition was
      predicted by the phase of alpha and by the power of beta (13-20Hz) oscillations.
      These evidence suggest that both periodic visual sampling mechanisms, reflected
      in the alpha phase, and network predisposition to extract local information,
      reflected in the beta power, predispose to object discrimination in a crowded
      scene.

PMID- 28506434
TI  - ERP signatures of conscious and unconscious word and letter perception in an
      inattentional blindness paradigm.
AB  - A three-phase inattentional blindness paradigm was combined with ERPs. While
      participants performed a distracter task, line segments in the background formed
      words or consonant-strings. Nearly half of the participants failed to notice
      these word-forms and were deemed inattentionally blind. All participants noticed
      the word-forms in phase 2 of the experiment while they performed the same
      distracter task. In the final phase, participants performed a task on the word
      forms. In all phases, including during inattentional blindness, word-forms
      elicited distinct ERPs during early latencies (~200-280ms) suggesting unconscious
      orthographic processing. A subsequent ERP (~320-380ms) similar to the visual
      awareness negativity appeared only when subjects were aware of the word-forms,
      regardless of the task. Finally, word-forms elicited a P3b (~400-550ms) only when
      these stimuli were task-relevant. These results are consistent with previous
      inattentional blindness studies and help distinguish brain activity associated
      with pre- and post-perceptual processing from correlates of conscious perception.

PMID- 28506435
TI  - A Practical Approach and Model of Care for HCV Treatment With Direct Acting
      Antivirals in an Urban Setting.

PMID- 28506436
TI  - Silence = Defunding, New Infections, Social Injustice, and Death.

PMID- 28506437
TI  - Association Between Interleukin-6 and Striatal Prediction-Error Signals Following
      Acute Stress in Healthy Female Participants.
AB  - BACKGROUND: Stress is widely known to alter behavioral responses to rewards and
      punishments. It is believed that stress may precipitate these changes through
      modulation of corticostriatal circuitry involved in reinforcement learning and
      motivation, although the intervening mechanisms remain unclear. One candidate is
      inflammation, which can rapidly increase following stress and can disrupt
      dopamine-dependent reward pathways. METHODS: Here, in a sample of 88 healthy
      female participants, we first assessed the effect of an acute laboratory stress
      paradigm on levels of plasma interleukin-6 (IL-6), a cytokine known to be both
      responsive to stress and elevated in depression. In a second laboratory session,
      we examined the effects of a second laboratory stress paradigm on reward
      prediction error (RPE) signaling in the ventral striatum. RESULTS: We show that
      individual differences in stress-induced increases in IL-6 (session 1) were
      associated with decreased ventral striatal RPE signaling during reinforcement
      learning (session 2), though there was no main effect of stress on RPE.
      Furthermore, changes in IL-6 following stress predicted intraindividual
      variability in perceived stress during a 4-month follow-up period. CONCLUSIONS:
      Taken together, these data identify a novel link between IL-6 and striatal RPEs
      during reinforcement learning in the context of acute psychological stress, as
      well as future appraisal of stressful life events.

PMID- 28506439
TI  - Clinical Review: Loperamide Toxicity.
AB  - Loperamide is a nonprescription opioid widely used for the treatment of diarrhea.
      Although it is relatively safe at therapeutic doses, increasing reports describe
      its misuse and abuse at very high doses either for euphoric effects or to
      attenuate symptoms of opioid withdrawal. Life-threatening loperamide toxicity can
      result from the relatively new clinical syndrome of loperamide-induced cardiac
      toxicity. These patients are often young and may present in cardiac arrest or
      with unheralded, recurrent syncope in conjunction with ECG abnormalities,
      including marked QT-interval prolongation, QRS-interval widening, and ventricular
      dysrhythmias. Features of conventional opioid toxicity may also be present. The
      mainstays of treatment include advanced cardiac life support and supportive care,
      although selected patients may be candidates for overdrive pacing, intravenous
      lipid emulsion, or extracorporeal membrane oxygenation. In patients who survive
      loperamide toxicity, consideration should be given to the treatment of an
      underlying opioid use disorder, if present.

PMID- 28506438
TI  - Prion-like Spreading in Tauopathies.
AB  - Tau is a microtubule-associated protein that functions in regulating cytoskeleton
      dynamics, especially in neurons. Misfolded and aggregated forms of tau produce
      pathological structures in a number of neurodegenerative diseases, including
      Alzheimer's disease (AD) and tauopathy dementias. These disorders can present
      with a sporadic etiology, such as in AD, or a familial etiology, such as in some
      cases of frontotemporal dementia with parkinsonism. Notably, the pathological
      features of tau pathology in these diseases can be very distinct. For example,
      the tau pathology in corticobasal degeneration is distinct from that of an AD
      patient. A wealth of evidence has emerged within the last decade to suggest that
      the misfolded tau in tauopathies possesses prion-like features and that such
      features may explain the diverse characteristics of tauopathies. The prion-like
      concept for tauopathies arose initially from the observation that the progressive
      accumulation of tau pathology as the symptoms of AD progress seemed to follow
      anatomically linked pathways. Subsequent studies in cell and animal models
      revealed that misfolded tau can propagate from cell to cell and from region to
      region in the brain through direct neuroanatomical connections. Studies in these
      cell and mouse models have demonstrated that experimentally propagated forms of
      misfolded tau can exist as conformationally distinct "strains" with unique
      biochemical, morphological, and neuropathological characteristics. This review
      discusses the clinical, pathological, and genetic diversity of tauopathies and
      the discoveries underlying the emerging view that the unique features of
      clinically distinct tauopathies may be a reflection of the strain of misfolded
      tau that propagates in each disease.

PMID- 28506440
TI  - The Wistar Audiogenic Rat (WAR) strain and its contributions to epileptology and
      related comorbidities: History and perspectives.
AB  - In the context of modeling epilepsy and neuropsychiatric comorbidities, we review
      the Wistar Audiogenic Rat (WAR), first introduced to the neuroscience
      international community more than 25years ago. The WAR strain is a genetically
      selected reflex model susceptible to audiogenic seizures (AS), acutely mimicking
      brainstem-dependent tonic-clonic seizures and chronically (by audiogenic
      kindling), temporal lobe epilepsy (TLE). Seminal neuroethological,
      electrophysiological, cellular, and molecular protocols support the WAR strain as
      a suitable and reliable animal model to study the complexity and emergent
      functions typical of epileptogenic networks. Furthermore, since epilepsy
      comorbidities have emerged as a hot topic in epilepsy research, we discuss the
      use of WARs in fields such as neuropsychiatry, memory and learning,
      neuroplasticity, neuroendocrinology, and cardio-respiratory autonomic regulation.
      Last, but not least, we propose that this strain be used in "omics" studies, as
      well as with the most advanced molecular and computational modeling techniques.
      Collectively, pioneering and recent findings reinforce the complexity associated
      with WAR alterations, consequent to the combination of their genetically
      dependent background and seizure profile. To add to previous studies, we are
      currently developing more powerful behavioral, EEG, and molecular methods,
      combined with computational neuroscience/network modeling tools, to further
      increase the WAR strain's contributions to contemporary neuroscience in addition
      to increasing knowledge in a wide array of neuropsychiatric and other
      comorbidities, given shared neural networks. During the many years that the WAR
      strain has been studied, a constantly expanding network of multidisciplinary
      collaborators has generated a growing research and knowledge network. Our current
      and major wish is to make the WARs available internationally to share our
      knowledge and to facilitate the planning and execution of multi-institutional
      projects, eagerly needed to contribute to paradigm shifts in epileptology. This
      article is part of a Special Issue entitled "Genetic and Reflex Epilepsies,
      Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

PMID- 28506441
TI  - Association of traumatic brain injury and Alzheimer disease onset: A systematic
      review.
AB  - BACKGROUND: Inconsistencies regarding the risk of developing Alzheimer disease
      after traumatic brain injury (TBI) remain in the literature. Indeed, why AD
      develops in certain TBI patients while others are unaffected is still unclear.
      OBJECTIVE: The aim of this study was to performed a systematic review to
      investigate whether certain variables related to TBI, such as TBI severity, loss
      of consciousness (LOC) and post-traumatic amnesia (PTA), are predictors of risk
      of AD in adults. METHODS: From 841 citations retrieved from MEDLINE via PubMed,
      EMBASE, PSYINFO and Cochrane Library databases, 18 studies were eligible for the
      review. RESULTS: The review revealed that about 55.5% of TBI patients may show
      deteriorated condition, from acute post-TBI cognitive deficits to then meeting
      diagnostic criteria for AD, but whether TBI is a risk factor for AD remains
      elusive. CONCLUSIONS: Failure to establish such a link may be related to
      methodological problems in the studies. To shed light on this dilemma, future
      studies should use a prospective design, define the types and severities of TBI
      and use standardized AD and TBI diagnostic criteria. Ultimately, an AD prediction
      model, based on several variables, would be useful for clinicians detecting TBI
      patients at risk of AD.

PMID- 28506442
TI  - Boosting syntax training with temporally regular musical primes in children with
      cochlear implants.
AB  - OBJECTIVES: Previous research has suggested the use of rhythmic structures
      (implemented in musical material) to improve linguistic structure processing
      (i.e., syntax processing), in particular for populations showing deficits in
      syntax and temporal processing (e.g., children with developmental language
      disorders). The present study proposes a long-term training program to improve
      syntax processing in children with cochlear implants, a population showing syntax
      processing deficits in perception and production. METHODS: The training program
      consisted of morphosyntactic training exercises (based on speech processing) that
      were primed by musical regular primes (8 sessions) or neutral baseline primes
      (environmental sounds) (8 sessions). A crossover design was used to train 10 deaf
      children with cochlear implants. Performance in grammatical processing, non-word
      repetition, attention and memory was assessed before and after training. RESULTS:
      Training increased performance for syntax comprehension after both prime types
      but for grammaticality judgements and non-word repetition only when musical
      primes were used during training. For the far-transfer tests, some effects were
      also observed for attention tasks, especially if fast and precise sequential
      analysis (sequencing) was required, but not for memory tasks. CONCLUSIONS: The
      findings extend the previously observed beneficial short-term effects of regular
      musical primes in the laboratory to long-term training effects. Results suggest
      that the musical primes improved the processing of the syntactic training
      material, thus enhancing the training effects on grammatical processing as well
      as phonological processing and sequencing of speech signals. The findings can be
      interpreted within the dynamic attending theory (postulating the modulation of
      attention over time) and associated oscillatory brain activity. Furthermore, the
      findings encourage the use of rhythmic structures (even in non-verbal materials)
      in language training programs and outline perspectives for rehabilitation.

PMID- 28506444
TI  - Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell
      function.
AB  - BACKGROUND AIMS: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19
      has demonstrated remarkable success in targeting B-cell malignancies but is often
      complicated by serious systemic toxicity in the form of cytokine release syndrome
      (CRS). CRS symptoms are primarily mediated by interleukin 6 (IL-6), and clinical
      management has focused on inhibition of IL-6 signaling. The cellular source and
      function of IL-6 in CRS remain unknown. METHODS: Using co-culture assays and data
      from patients on our clinical CAR T-cell trials, we investigated the cellular
      source of IL-6, as well as other CRS-associated cytokines, during CAR T-cell
      activation. We also explored the effect that IL-6 has on T-cell function.
      RESULTS: We demonstrated that IL-6 is secreted by monocyte-lineage cells in
      response to CAR T-cell activation in a contact-independent mechanism upon T-cell
      engagement of target leukemia. We observed that the presence of antigen
      presenting cell-derived IL-6 has no impact on CAR T-cell transcriptional profiles
      or cytotoxicity. Finally, we confirm that CAR T cells do not secrete IL-6 in vivo
      during clinical CRS. DISCUSSION: These findings suggest that IL-6 blockade will
      not affect CD19 CAR T-cell-driven anti-leukemic cytotoxicity, permitting enhanced
      control of CRS while maintaining CAR T-cell efficacy.

PMID- 28506445
TI  - Comparison of Features of Fatal Versus Nonfatal Cardiac Arrest in Patients With
      Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
AB  - Once arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      diagnosed, the incidence of sudden cardiac death (SCD) is rare and prognosis is
      favorable, highlighting the value of early disease recognition. To inform
      strategies to diagnose ARVD/C before SCD, we sought to characterize clinical,
      genetic, and family history features of ARVD/C cases first recognized after SCD
      or resuscitated SCD (sudden cardiac arrest [SCA]). We identified 66 ARVD/C cases
      submitted to the Johns Hopkins ARVD/C Registry in whom disease was first
      recognized after SCD (n = 45) or SCA (n = 21) and compared their clinical,
      genetic, and demographic features with 352 patients (227 probands) diagnosed with
      ARVD/C by 2010 Task Force Criteria before any arrest. SCD/SCA cases were 65% men
      and experienced their arrest at 29.3 +/- 13.8 years. Exertion precipitated 72% of
      arrests. Family history was recognized before arrest in 11 cases (17%), and 24
      cases (41%) had reported cardiac symptoms before arrest. The SCD/SCA cohort was
      disproportionately men (65% SCD/SCA vs 50% living, p = 0.03) and younger at both
      first reported symptom (27.7 +/- 13.5 years SCD/SCA vs 33.0 +/- 13.6 years
      living, p = 0.01) and first sustained ventricular arrhythmia (VA) (29.3 +/- 13.8
      years SCD/SCA vs 35.6 +/- 12.9 years living, p <0.001). In addition, survival
      from first symptom to VA was significantly shorter in SCD/SCA cases (p <0.001).
      These results suggest that the natural history of ARVD/C may be accelerated in
      SCD/SCA cases. In conclusion, although symptoms or family history provide a
      window of opportunity for diagnosis before death, time to intervene after symptom
      onset is limited.

PMID- 28506443
TI  - Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling
      and homeostasis.
AB  - The human selenoprotein family contains 25 members that share the common feature
      of containing the amino acid, selenocysteine (Sec). Seven selenoproteins are
      localized to the endoplasmic reticulum (ER) and exhibit different structural
      features contributing to a range of cellular functions. Some of these functions
      are either directly or indirectly related to calcium (Ca2+) flux or homeostasis.
      The presence of the unique Sec residue within these proteins allows some to exert
      oxidoreductase activity, while the function of the Sec in other ER selenoproteins
      remains unclear. Some functional insight has been achieved by identifying domains
      within the ER selenoproteins or through the identification of binding partners.
      For example, selenoproteins K and N (SELENOK AND SELENON) have been characterized
      through interactions detected with the inositol 1,4,5-triphosphate receptors
      (IP3Rs) and the SERCA2b pump, respectively. Others have been linked to chaperone
      functions related to ER stress or Ca2+ homeostasis. This review summarizes the
      details gathered to date regarding the ER-resident selenoproteins and their
      effect on Ca2+ regulated pathways and outcomes in cells.

PMID- 28506446
TI  - Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3
      Supplementation in patients with chronic kidney disease on hemodialysis.
AB  - BACKGROUND & AIMS: While vitamin D deficiency is common in patients with end
      stage renal disease on dialysis and treatment with Vitamin D2 and Vitamin D3 is
      becoming increasingly common in these patients, little is known about
      24,25(OH)2D3 metabolite production. Some authors report that the CYP24A1 enzyme
      is upregulated in CKD, but reports of low serum levels of 24,25(OH)2D3 in these
      patients bring this into question. Lack of substrate or increased clearance of
      the metabolite have been proposed as possible causes. We report serum
      24,25(OH)2D3 levels from three controlled trials of Vitamin D2 and Vitamin D3
      supplementation which reached adequate levels of 25(OH)D in patients with end
      stage renal disease on dialysis. METHODS: 680 samples from three controlled
      trials of Vitamin D2 or Vitamin D3 supplementation in CKD Stage 5D were available
      for analysis. The trials used single doses of 50,000 IU Vitamin D3, or 50,000 IU
      Vitamin D2, or weekly doses of 10,000 IU or 20,000 IU Vitamin D3. Blood samples
      were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D
      and 24,25(OH)2D3 levels were measured using a novel, very sensitive LC-MS/MS
      based method involving derivatization with DMEQ-TAD. Linear mixed effect
      regression models were used to compare the 3 studies and the interventions within
      studies over time. RESULTS: The subjects given Vitamin D3 had significant
      increases in 25(OH)D levels. Serum 24,25(OH)2D3 levels were low at baseline in
      the renal patients and rose slightly with native vitamin D supplementation, but
      these levels were lower than reports of 24,25(OH)2D3 in healthy populations.
      CONCLUSIONS: We conclude that the enzymatic activity of CYP24A1 is abnormal in
      end stage renal patients on dialysis. These trials were registered on
      clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and
      NCT01675557 on 8/28/2012.

PMID- 28506448
TI  - The differential effects of changes in individual macronutrient intake on changes
      in lipid concentrations during childhood: From the Ewha Birth & Growth Cohort.
AB  - BACKGROUND & AIMS: High carbohydrate or fat intake is responsible for abnormal
      lipid concentrations in adults, but few studies of children have been reported.
      Using data from a Korean children's cohort study, we assessed the association
      between macronutrient intake and lipid profile with a longitudinal association
      during a 4-year follow-up. METHODS: Using 2 days of 24-h dietary data obtained at
      3 (n = 323) and 7 (n = 292) years old from the Ewha Birth & Growth Cohort, we
      calculated changes (n = 103) in macronutrient intake in terms of energy-adjusted
      intake and percent total energy for nutrients. Changes in lipid profiles (TC:
      total cholesterol, TG: triglyceride, HDL-c: high-density lipoprotein cholesterol,
      LDL-c: low-density lipoprotein cholesterol) are the primary outcomes in this
      study. The effects of individual changes in macronutrient intake on changes in
      lipid profiles over time were assessed using multiple regression analyses.
      RESULTS: The percentages of total energy from carbohydrates and fat were 59.1%
      and 27.4% at baseline, respectively. Those in the highest tertile of carbohydrate
      intake showed the highest mean TG and lowest mean TC and HDL-c levels, regardless
      of observation time. By contrast, those with the highest fat intake indicated the
      lowest mean TG and highest mean TC and HDL-c at 7 years old. In addition,
      increased intake of carbohydrates had an unfavorable effect on TG, while
      increased intake of fat, especially animal-based fat, increased LDL-c levels over
      time. CONCLUSIONS: Our study showed that a relatively high intake of carbohydrate
      or fat among children had an unfavorable effect on lipid concentrations based on
      a longitudinal approach.

PMID- 28506447
TI  - Effects of continuous use of probiotics before liver transplantation: A
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND & AIMS: Although there is increasing evidence for the benefits of
      probiotics in patients with liver diseases, data on the benefits of pre-LT
      administration of probiotics are lacking. The aim of this study was to evaluate
      the effects of continuous administration of probiotics before liver
      transplantation (LT) on pre- and post-transplant patient outcomes. METHODS: In
      this randomized, double-blind, and placebo-controlled trial adult cirrhotic
      patients listed for LT received a 4-strain probiotic preparation or placebo daily
      from enrollment until LT. The primary outcome measures were postoperative
      mortality and infection rates. The secondary outcome measures were 5-day post
      transplant aspartate and alanine aminotransferase activities, bilirubin
      concentration, and international normalized ratio; waiting-list mortality; pre
      transplant Model for End-stage Liver Disease score and Child-Turcotte-Pugh class
      changes; and pre-transplant infections. RESULTS: A total of 55 patients were
      randomized. The 90-day postoperative mortality rates were 0% and 4.3% in the
      probiotic and placebo groups, respectively (p > 0.99). Patients receiving
      probiotics had significantly reduced 30-day (4.8% versus 34.8%, p = 0.02) and 90
      day (4.8% versus 47.8%, p = 0.002) infection rates, lower post-LT bilirubin
      concentration (p = 0.02), and more rapid decrease of aspartate (p = 0.03) and
      alanine (p = 0.03) aminotransferase activities. Probiotics did not have
      significant effects on other secondary outcome measures. CONCLUSIONS: Although
      continuous administration of probiotics before LT does not appear to affect
      postoperative mortality, it effectively prevents postoperative infections and
      improves early biochemical parameters of allograft function. CLINICALTRIALS. GOV
      IDENTIFIER: NCT01735591.

PMID- 28506450
TI  - Utility and versatility of the supraclavicular artery island flap in head and
      neck reconstruction.
AB  - INTRODUCTION: The supraclavicular island flap is a rotational pedicled flap and
      may have some advantages in head and neck reconstruction compared with free
      tissue transfer when this kind of reconstruction is not affordable or
      recommended. MATERIAL AND METHODS: We present our experience during the year 2016
      in the application of the supraclavicular island flap in five cases as an
      alternative to microvascular reconstruction in several defects after resection of
      head and neck tumours. In two patients, the flap was used to close the surgical
      pharyngostoma after total laryngectomy with partial pharyngectomy. In one
      patient, it was used in lateral facial reconstruction after partial resection of
      the temporal bone. In one case, it was used to close a skin defect after total
      laryngectomy with prelaryngeal tissue extension. And in the last case to close a
      neck skin defect after primary closure of a pharyngo-cutaneous fistula. There
      were no flap complications, and the result was satisfactory in all cases.
      RESULTS: The supraclavicular artery island flap is useful and versatile in head
      and neck reconstruction. Operating room time in aged patients or those with
      comorbidities will be reduced compared to free flaps. The surgical technique is
      relatively easy and can be used for skin and mucosal coverage. CONCLUSION: The
      supraclavicular island flap could be a recommended option in head and neck
      reconstruction, its use seems to be increasing and provides a safe and time
      saving option to free flaps in selected patients.

PMID- 28506449
TI  - Improved growth, tolerance and intake with an extensively hydrolysed peptide feed
      in infants with complex disease.
AB  - BACKGROUND & AIMS: Infants with complex medical conditions often display
      faltering growth due to elevated nutritional requirements, poor intake and
      intolerance of feeding with malabsorption and maldigestion. As a result their
      nutritional management can be extremely challenging and enteral nutritional
      support is required. This study aimed to investigate the effectiveness, tolerance
      and acceptability of nutritional support with a specially formulated, paediatric
      peptide feed in infants with complex disease and signs of growth faltering with
      their current nutritional management. METHODS: This prospective intervention
      study investigated gastrointestinal (GI) tolerance, nutritional intake and
      compliance with feeding, anthropometry and growth in 18 infants (mean age 6.11
      months +/- 4.69, mean weight 4.97 kg +/- 1.71) during 28 days of enteral
      nutritional support with a paediatric (1 kcal/ml) readymade peptide feed.
      RESULTS: GI tolerance to nutritional support with a peptide enteral feed was good
      and either improved or remained stable over the study. Compliance was excellent
      (94.0% +/- 12.6), total energy intake improved (+23 +/- 42 kcal/kg, p = 0.037)
      and mean weight (0.61 kg +/- 0.31, p = 0.0001), length (1.89 +/- 1.77 cm, p =
      0.0001), head circumference (1.33 +/- 1.29 cm, p = 0.001), weight for length Z
      score (p < 0.05), and weight for age Z score (p < 0.05) significantly improved.
      Sixty one percent (n = 11) of the infants showed signs of increased growth
      velocity, moving upwards in terms of their centiles. All 18 infants continued
      with the paediatric, peptide enteral feed once the study was complete.
      CONCLUSIONS: This prospective study showed that nutrition support with a
      specially formulated, paediatric peptide readymade feed was well tolerated,
      helped to promote growth, and can be considered suitable for use in infants with
      complex disease and faltering growth who are unable to tolerate a whole protein
      feed.

PMID- 28506451
TI  - Motor skill development in low-income, at-risk preschoolers: A community-based
      longitudinal intervention study.
AB  - OBJECTIVES: This study aimed to: (1) determine the status of fundamental movement
      skill (FMS) performance in low-income, at-risk preschoolers; and (2) evaluate the
      impact of the Food Friends Get Movin' with Mighty Moves (MM) program on improving
      children's FMS at two-year follow-up. DESIGN: Longitudinal, quasi-experimental
      study with matched controls. METHODS: The Colorado LEAP study was conducted in
      four Head Start/preschools (two intervention, two control) serving children aged
      3-5 years. MM was delivered to the intervention group during preschool. The
      Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) subtests
      for balance, running speed and agility, upper-limb coordination (object control
      (OC) skills) and strength were administered to children at baseline, post
      intervention in preschool, one-year follow-up (kindergarten), and two-year follow
      up (first grade). RESULTS: Compared to the normative sample's mean, the mean
      scaled score for all participants at baseline was significantly lower for balance
      (p=0.016) and OC skills (p<0.001). At two-year follow-up, the means of balance
      for all participants and OC skills for just the control group were significantly
      lower than those of the normative sample (p<=0.001). Hierarchical linear
      regression analyses revealed a significant intervention effect for OC skills with
      the overall model accounting for 41% of variance at two-year follow-up,
      F(6,165)=20.45, p<0.001. No intervention effects were found for the other three
      BOT-2 subtests. CONCLUSIONS: Delivering the MM program in preschool confers a
      lasting impact on FMS, specifically OC skills, in at-risk elementary school
      children. Results suggest that at-risk preschoolers are already behind in FMS
      development and these delays will continue through first grade.

PMID- 28506452
TI  - Performing nuclear medicine examinations in pregnant women.
AB  - The number of nuclear medicine examinations performed worldwide has been steadily
      increasing over the last few years. By consequence, an ever increasing number of
      pregnant women are likely to be exposed to radioisotopes. The range of doses
      encountered in nuclear medicine practice is well below the threshold for
      deterministic effects, such as embryonic death, birth defects or mental
      retardation. According to the linear no-threshold hypothesis, however, stochastic
      effects (e.g. an increased risk of cancer) remain possible even at this dose
      range. This purely hypothetical radiation risk to the fetus should however be put
      in perspective with the risk of having a scan of low diagnostic quality for a
      life-threatening medical condition. In recent years there has been a push to
      reduce as much as possible the dose from radiological imaging, for example by
      using acquisition protocols specific to pregnant women and by injecting lower
      activities. These approaches, in our opinion, overweigh the radiation risk and
      actually may put the life of both the mother and the fetus in danger. Since
      imaging protocols already seek to use the lowest possible dose compatible with a
      quality scan for all patients, pregnant women should be imaged using the
      protocols applied to any other patient. Encouraging bladder voiding by natural
      means after injection will significantly reduce fetal exposure without
      compromising image quality.

PMID- 28506453
TI  - Challenges of dosimetry of ultra-short pulsed very high energy electron beams.
AB  - Very high energy electrons (VHEE) in the range from 100 to 250MeV have the
      potential of becoming an alternative modality in radiotherapy because of their
      improved dosimetric properties compared with 6-20MV photons generated by clinical
      linear accelerators (LINACs). VHEE beams have characteristics unlike any other
      beams currently used for radiotherapy: femtosecond to picosecond duration
      electron bunches, which leads to very high dose per pulse, and energies that
      exceed that currently used in clinical applications. Dosimetry with conventional
      online detectors, such as ionization chambers or diodes, is a challenge due to
      non-negligible ion recombination effects taking place in the sensitive volumes of
      these detectors. FLUKA and Geant4 Monte Carlo (MC) codes have been employed to
      study the temporal and spectral evolution of ultrashort VHEE beams in a water
      phantom. These results are complemented by ion recombination measurements
      employing an IBA CC04 ionization chamber for a 165MeV VHEE beam. For comparison,
      ion recombination has also been measured using the same chamber with a
      conventional 20MeV electron beam. This work demonstrates that the IBA CC04
      ionization chamber exhibits significant ion recombination and is therefore not
      suitable for dosimetry of ultrashort pulsed VHEE beams applying conventional
      correction factors. Further study is required to investigate the applicability of
      ion chambers in VHEE dosimetry.

PMID- 28506454
TI  - Esophageal intramural pseudodiverticulosis, a rare cause of stenosis.

PMID- 28506455
TI  - Trauma morning report is the ideal environment to teach and evaluate resident
      communication and sign-outs in the 80 hour work week.
AB  - BACKGROUND: The 80h work week has raised concerns that complications may increase
      due to multiple sign-outs or poor communication. Trauma Surgery manages complex
      trauma and acute care surgical patients with rapidly changing physiology,
      clinical demands and a large volume of data that must be communicated to render
      safe, effective patient care. Trauma Morning Report format may offer the ideal
      situation to study and teach sign-outs and resident communication. MATERIALS AND
      METHODS: Surgery Residents were assessed on a 1-5 scale for their ability to
      communicate to their fellow residents. This consisted of 10 critical points of
      the presentation, treatment and workup from the previous night's trauma
      admissions. Scores were grouped into three areas. Each area was scored out of 15.
      Area 1 consisted of Initial patient presentation. Area 2 consisted of events in
      the trauma bay. Area 3 assessed clarity of language and ability to communicate to
      their fellow residents. The residents were assessed for inclusion of pertinent
      positive and negative findings, as well as overall clarity of communication. In
      phase 1, residents were unaware of the evaluation process. Phase 2 followed a
      series of resident education session about effective communication, sign-out
      techniques and delineation of evaluation criteria. Phase 3 was a resident-blinded
      phase which evaluated the sustainability of the improvements in resident
      communication. RESULTS: 50 patient presentations in phase 1, 200 in phase 2, and
      50 presentations in phase 3 were evaluated. Comparisons were made between the
      Phase 1 and Phase 2 evaluations. Area 1 (initial events) improved from 6.18 to
      12.4 out of 15 (p<0.0001). Area 2 (events in the trauma bay) improved from 9.78
      to 16.53 (p<0.0077). Area 3 (communication and language) improved from 8.36 to
      12.22 out of 15 (P<0.001). Phase 2 to Phase 3 evaluations were similar, showing
      no deterioration of skills. CONCLUSIONS: Trauma Surgery manages complex surgical
      patients, with rapidly changing physiologic and clinical demands. Trauma Morning
      Report, with diverse attendance including surgical attendings and residents in
      various training years, is the ideal venue for real-time teaching and evaluation
      of sign-outs and reinforcing good communication skills in residents.

PMID- 28506456
TI  - Prevalence of Asymptomatic Coronary Heart Disease in the Siblings of Young
      Myocardial Infarction Patients as Detected by Coronary Computer Tomography
      Angiography: A Pilot Study.
AB  - BACKGROUND: There is little data on the prevalence of coronary heart disease
      (CHD) in the young. The study aimed to estimate the prevalence of asymptomatic
      CHD in siblings of young patients with myocardial infarction (MI) using coronary
      computed tomography angiography (CCTA). METHODS: Prospective observational data
      was collected on siblings of patients aged <=55 years presenting with acute MI
      and having coronary stenosis >=50% on invasive coronary angiography in at least
      one epicardial coronary artery. Inclusion criteria included ages 30-55 and 30-60
      years for males and females respectively. Outcome of interest was obstructive CHD
      by coronary computer tomography angiography (CCTA), which was defined by either
      moderate (50-69% stenosis) and/or severe (>=70% stenosis). RESULTS: Fifty
      participants were studied of whom 20 (40%) were male. Thirty (60%) were current
      or ex-smokers, 4 (8%) had diabetes, 8 (16%) had hypertension and 26 (52%) had
      dyslipidaemia. Obstructive CHD by CCTA was detected in 9 (18%, 95% CI 9%-31%)
      participants and 3 (6%, 95% CI 1%-17%) participants were found to have severe
      luminal stenosis. The median radiation dose was 3.9 (IQR 0.9) mSv. CONCLUSIONS:
      Approximately a fifth of siblings of young MI patients were found to have
      asymptomatic but obstructive CHD detected on CCTA of which one third was severe.
      This is a group in whom screening for CHD warrants further investigation.

PMID- 28506457
TI  - Early Thrombosis and Non-Heparin-Coated Pulmonary Artery Catheters.

PMID- 28506458
TI  - Impact of Postoperative Hypothermia on Outcomes in Coronary Artery Bypass Surgery
      Patients.
AB  - OBJECTIVES: To determine the impact of postoperative hypothermia on outcomes in
      coronary artery bypass graft surgery (CABG) patients. DESIGN: A retrospective
      study was performed on patients who underwent isolated CABG between 2011 and
      2014. SETTING: Single-center study at a university hospital. PARTICIPANTS: All
      patients who underwent isolated CABG with cardiopulmonary bypass between 2011 and
      2014. INTERVENTIONS: Patients underwent isolated CABG on cardiopulmonary bypass.
      MEASUREMENTS AND MAIN RESULTS: Patients were propensity-score matched based on
      the likelihood of being hypothermic (<36oC) or normothermic (>=36oC) on arrival
      to the cardiac surgery intensive care unit (ICU) from the operating room. Total
      transfusion requirements, composite in-hospital morbidity and/or mortality
      endpoint, total hours in the ICU, and length of hospital stay were compared
      between the 2 groups. Of the 1,030 patients undergoing isolated CABG, 529 (51.3%)
      were hypothermic on arrival to the ICU. The hypothermic cohort were older, had
      more females, had lower body mass indices, had lower starting hematocrit values,
      were cooled to lower temperatures while on cardiopulmonary bypass, and had longer
      cardiopulmonary bypass runs compared with the normothermic group. Of the 748
      patients who were propensity matched, there were no differences in blood and
      blood product transfusion requirements, mortality and complication rates, time on
      the ventilator, length of ICU stay, and length of hospital stay between
      hypothermic and normothermic patients. CONCLUSIONS: Hypothermia at ICU admission
      after CABG was not associated with increased adverse outcomes, possibly
      suggesting that complete rewarming before separation from cardiopulmonary bypass
      may not be essential in all patients.

PMID- 28506459
TI  - Increased Mitral Gradient After Transcatheter Aortic Valve Replacement: Is It
      Anatomic Mitral Valve Obstruction Or Related to Hemodynamics?

PMID- 28506460
TI  - Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin
      Recruitment by RNF168/169 and RAD18.
AB  - The protein 53BP1 plays a central regulatory role in DNA double-strand break
      repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono
      ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated
      at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin
      ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance
      (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and
      histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to
      form a high-affinity complex. This conformational selection mechanism contrasts
      with the low-affinity binding mode of 53BP1, and it ensures 53BP1 displacement by
      RNF169 from NCP-ubme. We also show that RAD18 binds tightly to NCP-ubme through a
      ubiquitin-binding domain that contacts ubiquitin and nucleosome surfaces accessed
      by 53BP1. Our work uncovers diverse ubiquitin recognition mechanisms in the
      nucleosome, explaining how RNF168, RNF169, and RAD18 regulate 53BP1 chromatin
      recruitment and how specificity can be achieved in the recognition of a ubiquitin
      modified substrate.

PMID- 28506461
TI  - MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death.
AB  - TNF is an inflammatory cytokine that upon binding to its receptor, TNFR1, can
      drive cytokine production, cell survival, or cell death. TNFR1 stimulation causes
      activation of NF-kappaB, p38alpha, and its downstream effector kinase MK2,
      thereby promoting transcription, mRNA stabilization, and translation of target
      genes. Here we show that TNF-induced activation of MK2 results in global RIPK1
      phosphorylation. MK2 directly phosphorylates RIPK1 at residue S321, which
      inhibits its ability to bind FADD/caspase-8 and induce RIPK1-kinase-dependent
      apoptosis and necroptosis. Consistently, a phospho-mimetic S321D RIPK1 mutation
      limits TNF-induced death. Mechanistically, we find that phosphorylation of S321
      inhibits RIPK1 kinase activation. We further show that cytosolic RIPK1
      contributes to complex-II-mediated cell death, independent of its recruitment to
      complex-I, suggesting that complex-II originates from both RIPK1 in complex-I and
      cytosolic RIPK1. Thus, MK2-mediated phosphorylation of RIPK1 serves as a
      checkpoint within the TNF signaling pathway that integrates cell survival and
      cytokine production.

PMID- 28506462
TI  - A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates
      Circadian Rhythms.
AB  - The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like
      1) is a regulatory hub for transcriptional coactivators and repressors that
      compete for binding and, consequently, contributes to period determination of the
      mammalian circadian clock. Here, we report the discovery of two distinct
      conformational states that slowly exchange within the dynamic TAD to control
      timing. This binary switch results from cis/trans isomerization about a highly
      conserved Trp-Pro imide bond in a region of the TAD that is required for normal
      circadian timekeeping. Both cis and trans isomers interact with transcriptional
      regulators, suggesting that isomerization could serve a role in assembling
      regulatory complexes in vivo. Toward this end, we show that locking the switch
      into the trans isomer leads to shortened circadian periods. Furthermore,
      isomerization is regulated by the cyclophilin family of peptidyl-prolyl
      isomerases, highlighting the potential for regulation of BMAL1 protein dynamics
      in period determination.

PMID- 28506463
TI  - RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD
      Phosphorylation, and Transcriptional Direction.
AB  - Eukaryotic genes are marked by conserved post-translational modifications on the
      RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3'
      profiles of these marks are established is poorly understood. Using pol II
      mutants in human cells, we found that slow transcription repositioned specific co
      transcriptionally deposited chromatin modifications; histone H3 lysine 36
      trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4
      dimethyl (H3K4me2) extended farther upstream of start sites. Slow transcription
      also evoked a hyperphosphorylation of CTD Ser2 residues at 5' ends of genes that
      is conserved in yeast. We propose a "dwell time in the target zone" model to
      explain the effects of transcriptional dynamics on the establishment of co
      transcriptionally deposited protein modifications. Promoter-proximal Ser2
      phosphorylation is associated with a longer pol II dwell time at start sites and
      reduced transcriptional polarity because of strongly enhanced divergent antisense
      transcription at promoters. These results demonstrate that pol II dynamics help
      govern the decision between sense and divergent antisense transcription.

PMID- 28506466
TI  - Impaired steroidogenesis in the testis of leptin-deficient mice (ob/ob -/-).
AB  - The obesity and its comorbidities, including resistance to leptin, impacts the
      reproductive function. Testes express leptin receptors in the germ cells and
      Leydig cells. Then, leptin-deficient animals are obese and infertile. We aimed to
      evaluate the structure and steroidogenic pathway of the testis of deficient
      leptin mice. Three months old male C57BL/6 mice (wild-type, WT) and deficient
      leptin (ob/ob) mice had their testes dissected and prepared for analyses.
      Compared to the WT group, the ob/ob group showed a greater body mass with smaller
      testes, and alterations in the germinative epithelium: fewer spermatogonia,
      spermatocytes, and spermatids. The Sertoli cells and the germ cells showed
      condensed nuclei and nuclear fragmentation indicating cell death, in agreement
      with a low expression of the proliferating cell nuclear antigen and a high
      expression of Caspase3. In the ob/ob group, the sperm was absent in the
      seminiferous tubules, and the steroidogenic pathway was compromised (low 3Beta
      hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein).
      Further, all hormone receptors involved in the testicular function were down
      expressed (androgen, estrogen, follicle-stimulating, luteinizing, aromatase, and
      nicotinamide adenine dinucleotide phosphate). In conclusion, the findings
      indicate significant morphological, hormonal and enzymatic changes in the testis
      of the ob/ob mice. The shifts in the enzymatic steroidogenic pathway and the
      enzymes related to spermatic activity support the insights about the failures in
      the fertility of these animals. The study provides new evidence and contributes
      to the understanding of how the lack of leptin and obesity might negatively
      modulate the testicular function leading to infertility.

PMID- 28506464
TI  - Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following
      Pneumonectomy.
AB  - To investigate the role of immune cells in lung regeneration, we used a
      unilateral pneumonectomy model that promotes the formation of new alveoli in the
      remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+
      and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the
      peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss
      of function in mice and adoptive transfer studies revealed that bone marrow
      derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine
      axis and are required for optimal lung regeneration, along with Il4ra-expressing
      leukocytes. Our data suggest that these cells modulate AEC2 proliferation and
      differentiation. Finally, we provide evidence that group 2 innate lymphoid cells
      are a source of IL-13, which promotes lung regeneration. Together, our data
      highlight the potential for immunomodulatory therapies to stimulate
      alveologenesis in adults.

PMID- 28506469
TI  - Sur la vitesse d'extinction d'une population dans un environnement aleatoire.
AB  - This study focuses on the speed of extinction of a population living in a random
      environment that follows a continuous-time Markov chain. Each individual dies or
      reproduces at a rate that depends on the environment. The number of offspring
      during reproduction follows a given probability law that also depends on the
      environment. In the so-called subcritical case where the population goes for sure
      to extinction, there is an explicit formula for the speed of extinction. In some
      sense, environmental stochasticity slows down population extinction.

PMID- 28506467
TI  - Apoptosis of bovine granulosa cells: Intracellular pathways and differentiation.
AB  - Follicular atresia in granulosa and theca cells occurs by apoptosis through weak
      hormonal stimulation. We have previously proposed an in vitro model to study this
      process by inducing apoptosis in BGC-1, a bovine granulosa cell line, and in
      primary cultures from ovaries with or without corpus luteum (CPGB+ and CPGB-,
      respectively), with different doses of gonadotropin releasing hormone (GnRH)
      analogs (leuprolide acetate (LA) as agonist and antide as antagonist). BGC-1
      represent immature granulosa cells, whereas CPGB represent different degrees of
      luteinization. Our aim was to evaluate the intracellular pathways involved in the
      GnRH regulation of apoptosis in BGC-1. Treatment with LA 100nM but not with
      antide led to an increase in BAX over BCL-2 expression, showing antagonism of
      antide. All treatments inhibited phospholipase-D (PLD) activity compared to
      control, implying agonist behavior of antide. Progesterone in vitro production
      and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) expression revealed different
      degrees of luteinization: BGC-1 were immature, whereas CPGB+ were less
      differentiated than CPGB-. We concluded that LA-induced apoptosis in BGC-1 occurs
      by activation of the mitochondrial pathway and by inhibition of PLD activity and
      that antide might work both as an antagonist of the intrinsic pathway and as an
      agonist of the extrinsic protection pathway by inhibiting PLD activity.

PMID- 28506468
TI  - [Impact of cork oak management on the ectomycorrhizal fungal diversity associated
      with Quercus suber in the Maamora forest (Morocco)].
AB  - The cork oak forest is an ecosystem playing a major role in Moroccan socio
      economy and biodiversity conservation. However, this ecosystem is negatively
      impacted by extensive human- and climate-driven pressures, causing a strong
      decrease in its distribution and a worsening of the desertification processes.
      This study aims at characterising the impact of cork oak forest management on a
      major actor of its functioning, the ectomycorrhizal (EcM) fungal community
      associated with Quercus suber, and the determination of EcM bio-indicators. The
      EcM fungal community has been monitored during spring and winter seasons in two
      sites of the Moroccan Maamora forest, corresponding to a forest site either
      impacted by human activities or protected. A significant impact of cork oak
      forest management on the EcM fungal community has been revealed, with major
      differences during the summer season. The results confirmed the potential
      ecological significance of several EcM fungi (e.g., Cenococcum) in the
      sustainability of the cork oak forest functioning, but also the significant
      association of certain EcM fungi (Pachyphloeus, Russula, Tomentella) with a
      perturbation or a season, and consequently to the cork oak forest status or to
      climatic conditions, respectively. The development of study at the Mediterranean
      scale may improve the robustness of ecological models to predict the impact of
      global changes on this emblematic ecosystem of Mediterranean basin.

PMID- 28506465
TI  - Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.
AB  - A detailed understanding of the paths that stem cells traverse to generate mature
      progeny is vital for elucidating the mechanisms governing cell fate decisions and
      tissue homeostasis. Adult stem cells maintain and regenerate multiple mature cell
      lineages in the olfactory epithelium. Here we integrate single-cell RNA
      sequencing and robust statistical analyses with in vivo lineage tracing to define
      a detailed map of the postnatal olfactory epithelium, revealing cell fate
      potentials and branchpoints in olfactory stem cell lineage trajectories.
      Olfactory stem cells produce support cells via direct fate conversion in the
      absence of cell division, and their multipotency at the population level reflects
      collective unipotent cell fate decisions by single stem cells. We further
      demonstrate that Wnt signaling regulates stem cell fate by promoting neuronal
      fate choices. This integrated approach reveals the mechanisms guiding olfactory
      lineage trajectories and provides a model for deconstructing similar hierarchies
      in other stem cell niches.

PMID- 28506470
TI  - Coronary CT angiography in the emergency department utilizing second and third
      generation dual source CT.
AB  - BACKGROUND: Coronary computed tomography angiography (coronary CTA) allows
      efficient triage of low to intermediate risk patients with suspected acute
      coronary syndrome (ACS) in the emergency department (ED). Techniques for coronary
      CTA acquisition in the ED continue to evolve with the establishment of
      standardized scan protocols and the introduction of newer generations of CT
      hardware. OBJECTIVES: To evaluate qualitative and quantitative image quality and
      radiation dose exposure of coronary CTA acquired on 2nd versus 3rd generation
      dual source CT (DSCT) scanners using a standardized institutional scan protocol
      designed for the ED. METHODS: A retrospective observational case-control study
      was performed of 246 ED patients referred to coronary CTA with suspicion of ACS
      (56.5% male; mean age 53.3 +/- 11.6 years) between October 2013 and August
      2015.123 consecutive patients were scanned on 3rd generation DSCT, and a cohort
      of 123 patients matched by age, BMI and heart rate were identified who had
      undergone 2nd generation DSCT imaging utilizing the same standard clinical
      protocol. Qualitative and quantitative image quality parameters and radiation
      exposures were evaluated. RESULTS: Qualitative image quality was significantly
      higher using 3rd generation DSCT as compared to 2nd generation (p < 0.001). Mean
      attenuation in the proximal coronary arteries was also significantly higher on
      3rd generation DSCT than for 2nd generation (586 HU vs. 426 HU in the left main
      coronary artery (LM), p < 0.001). Signal-to-noise ratio (SNR) and contrast-to
      noise ratio (CNR) values, however, were lower in 3rd generation DSCT than 2nd
      generation (SNR 11.2 [9.9-13.4] vs 13.5 [11.0-15.5] and CNR 12.4 [10.9-14.8] vs
      15.2 [12.8-17.9] in the LM, p < 0.001). Median effective dose was also lower for
      3rd generation DSCT than for 2nd generation (2.9 [2.3-5.0] mSv and 3.7 mSv [2.5
      5.7], respectively) although this trend did not reach statistical significance (p
      = 0.065). CONCLUSION: Qualitative image quality and mean CT attenuation values of
      the assessed coronary segments were significantly higher using 3rd generation
      DSCT. SNR and CNR were lower on 3rd generation DSCT, however this was accompanied
      by a trend toward lower radiation dose exposure when using the same standard
      institutional protocol.

PMID- 28506472
TI  - Gadolinium accumulation after contrast-enhanced magnetic resonance imaging: Which
      implications in patients with Crohn's disease?
AB  - Crohn's disease (CD) is a chronic inflammatory condition of the bowel,
      characterized by an alternation of remission and relapse phases, leading to a
      progressive intestinal damage with loss of function. Magnetic resonance
      enterography has been widely used in the past for the evaluation of fistulizing
      disease, but its use increased over time, being considered helpful in different
      moments of disease course. Intravenous injection of Gadolinium-based contrast
      agents has been demonstrated to be crucial to assess mucosal inflammation,
      transmural involvement, and extraintestinal disease. Recently, Gadolinium
      accumulation in human tissues has been increasingly reported, although clinical
      implications of this event are still unclear. In the present paper, we review the
      main evidence on the topic, focusing on the potential implications for
      gastroenterological practice.

PMID- 28506473
TI  - [Congenital lamellar cataract].

PMID- 28506471
TI  - Genetics of gonadotropins and their receptors as markers of ovarian reserve and
      response in controlled ovarian stimulation.
AB  - Several controlled ovarian stimulation (COS) protocols have been developed to
      increase the yield of mature oocytes retrieved in assisted reproductive
      techniques (ARTs). The ovarian reserve (OR) influences the COS response, and it
      represents the main parameter that helps clinicians in refining clinical
      treatments in the perspective of a "personalized" ART. This approach is even more
      needed in particular conditions such as poor OR or polycystic ovary syndrome.
      Follicle-stimulating hormone, luteinizing hormone, and human chorionic
      gonadotropin are currently used in COS at different combinations and with
      different efficacies, even if the best approach definition is controversial.
      Differences in individual-specific ovarian response to gonadotropin stimulation
      can be due to alterations of genes encoding for hormones or their receptors. In
      particular, FSHB c.-211G>T, FSHR p.Asn680Ser, and c.-29G>A SNP allelic
      combinations may be used as OR and COS response markers. The purpose of this
      review is to highlight the evidence-based relevance of mutations and
      polymorphisms in gonadotropins and their receptor genes as predictive markers of
      OR and COS response to achieve fine-tuned therapeutic regimens.

PMID- 28506474
TI  - [Retinal inner nuclear layer microcysts on spectral-domain OCT in alcoholic optic
      neuropathy].

PMID- 28506475
TI  - A novel perfused porcine simulator for teaching aortic anastomosis increases
      resident interest in vascular surgery.
AB  - OBJECTIVE: This report describes a novel simulator, euthanized pigs on
      cardiopulmonary bypass, and validates this simulator with a controlled trial in
      general surgery residents learning aortic anastomosis. We evaluated this novel
      simulator with the following hypothesis: our porcine perfused simulator is as
      good as or better than the standard rubber tubing, low-fidelity models used for
      vascular anastomotic training. METHODS: Euthanized pigs were placed on
      cardiopulmonary bypass, creating a perfused, ex vivo model on which to perform
      surgical procedures. The participants in the study were postgraduate year 2, 3,
      and 4 general surgery residents. Residents were randomized to practice aortic
      anastomosis in the pig laboratory (PL) simulator or in a dry laboratory. The PL
      residents and control residents performed a first vascular anastomosis on the
      rubber tube model. Anastomosis creation was filmed. The anastomosis and video
      were stored for later grading. Next, all residents underwent an ungraded, one-on
      one training session with the attending vascular surgeon. After the training
      session, all residents completed a second videotaped rubber tubing anastomosis.
      The grading scales used were validated by other authors: Global Assessment Score,
      Final Product Score, and Checklist Scoring Instrument. Survey data describing
      this experience were collected using a 13-question prelaboratory and 16-question
      postlaboratory questionnaires consisting of yes/no, multiple selection, and 5
      point Likert-type scale questions. RESULTS: All residents had a statistically
      significant improvement in time to completion and in the Global Assessment Score
      with tutored practice. The PL residents showed statistically significant
      improvement in completion time between the first and second videotaped
      anastomosis; however, there was no statistically significant improvement in the
      scoring metrics. The control residents showed statistically significant
      improvement in all three scoring metrics, but no statistically significant
      difference was found in completion time. The survey data showed a statistically
      significant shift in considering vascular surgery as a career after the
      experience in the PL group (P = .05) compared with the control group, who had no
      change in interest (P = .91). CONCLUSIONS: Our prospective, randomized clinical
      trial shows that the porcine cardiopulmonary bypass model achieves similar
      results to a previously validated bench top model while improving general surgery
      resident interest in vascular surgery as a career.

PMID- 28506476
TI  - Adherence to lipid management guidelines is associated with lower mortality and
      major adverse limb events in patients undergoing revascularization for chronic
      limb-threatening ischemia.
AB  - OBJECTIVE: The 2013 American College of Cardiology/American Heart Association
      lipid management guidelines recommend high-intensity statins for all patients
      <=75 years old with chronic limb-threatening ischemia (CLTI) and moderate
      intensity statins for CLTI patients >75 years old without contraindications or on
      dialysis, but these recommendations are based primarily on coronary and stroke
      data. We aimed to validate these guidelines in patients with CLTI and to assess
      current adherence to these recommendations. METHODS: We identified all patients
      with CLTI who underwent first-time revascularization (endovascular or surgical)
      at Beth Israel Deaconess Medical Center from 2005 to 2014. Patients were
      classified as taking high-intensity, moderate-intensity, low-intensity, or no
      statin postoperatively. Outcomes included death and major adverse limb event
      (MALE). Propensity scores were calculated for the probability of receiving
      guideline-recommended intensity of statin therapy to account for nonrandom
      assignment of treatments. Cox regression models were constructed and adjusted for
      the propensity scores and further adjusted for strong potential confounders.
      RESULTS: After excluding patients on hemodialysis (n = 252), we identified 1019
      limbs from 931 patients with a median follow-up of 380 days. Patients discharged
      on the recommended statin intensity had higher rates of preoperative statin use,
      coronary artery disease, chronic kidney disease, stroke, atrial fibrillation,
      congestive heart failure, and coronary artery bypass grafting; they had lower
      smoking rates and were less likely to be ambulatory preoperatively. Overall, only
      35% were taking the recommended statin dosage: 55% of those >75 years old and 20%
      of those <=75 years old. In multivariable analysis including propensity scores
      where appropriate, discharge on any statin was associated with lower mortality
      (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.90; P < .01).
      Discharge on the recommended intensity of statin therapy was associated with
      lower mortality (HR, 0.73; 95% CI, 0.60-0.99; P < .05) and lower MALE rate (HR,
      0.71; 95% CI, 0.51-0.97; P < .05). Patients >75 years old and <=75 years old
      accrued similar benefit. In patients >75 years old, moderate-intensity statin
      therapy was associated with lower rates of death and MALE compared with high
      intensity therapy but did not reach statistical significance. CONCLUSIONS: Use of
      the recommended intensity of statin therapy in compliance with 2013 American
      College of Cardiology/American Heart Association lipid management guidelines is
      associated with significantly improved survival and lower MALE rate in patients
      undergoing revascularization for CLTI. Adherence to current guidelines is an
      appealing target for quality improvement.

PMID- 28506479
TI  - The spectrum and management of noniatrogenic vascular trauma in the pediatric
      population.
AB  - BACKGROUND: To describe the spectrum of noniatrogenic pediatric vascular injuries
      and their outcomes at a large tertiary pediatric hospital. METHODS: Retrospective
      review of a prospectively-maintained trauma database, identifying children with
      noniatrogenic vascular injuries managed between 1994 and 2014. RESULTS: A total
      of 198 patients were identified. Those patients with a digital or intracerebral
      vascular injury (92/198) were excluded from further analysis. The remaining 106
      patients represented 1.2% of all traumas managed at our institution during the 21
      year study period. The majority were male (75%), and between 1 and 12years of age
      (71% of all patients). Median time from trauma scene to any hospital was 48min
      (range 0-132), and most patients were transferred from another hospital (64%).
      Three patients were declared dead upon arrival (3%). Penetrating injuries
      accounted for most injuries (72%), while blunt injuries accounted for the
      remainder. Ulnar, radial, or brachial artery trauma accounted for 47% of
      injuries. Most vessels were treated operatively, by primary repair (49%), vessel
      ligation (15%), or interposition graft (12%). Fourteen patients (13%) were
      managed nonoperatively and most patients (74%) experienced no complications in
      hospital or during follow-up. CONCLUSION: Noniatrogenic pediatric vascular
      injuries are rare and represent a highly heterogeneous population. Most children
      recover well, with minimal perioperative complications. LEVEL OF EVIDENCE: IV
      (case series with no comparison group).

PMID- 28506478
TI  - Metformin treatment does not affect the risk of ruptured abdominal aortic
      aneurysms.
AB  - OBJECTIVE: Diabetes counteracts formation and rupture of abdominal aortic
      aneurysms, possibly through arterial matrix accumulation. Use of metformin, on
      the other hand, reduces arterial accumulation of matrix molecules. Consequently,
      we hypothesized that metformin treatment may reverse the protective role of
      diabetes on the development and course of aneurysms, that is, that metformin
      would be associated with aneurysm rupture among individuals with diabetes.
      METHODS: Using nationwide Danish registry data, we performed a nested case
      control study on the association between long-term use of metformin and ruptured
      abdominal aortic aneurysm (RAAA). The source population was defined as all
      individuals in Denmark with diabetes. Cases were all individuals within the
      source population who were hospitalized with a primary diagnosis of RAAA. For
      each case, 10 controls matched by age and sex were randomly selected from the
      source population by risk set sampling. The main exposure measure was a
      cumulative dispensing of 1000 g of metformin between January 1995 and the index
      date. RESULTS: We identified 362 cases of RAAA during 1998 to 2013, of which
      83.7% occurred in men with a median age of 74 years. In total, 22.4% of the case
      population were long-term metformin users compared with 28.8% of the controls. We
      found a statistically nonsignificant protective effect of long-term metformin use
      toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00).
      When adjusted for covariates, OR increased to 0.84 (confidence interval, 0.61
      1.17). None of the subgroups had ORs deviating substantially from the main
      result. CONCLUSIONS: Metformin use does not increase the risk of RAAA among
      individuals with diabetes.

PMID- 28506477
TI  - Medical therapy and intervention do not improve uncomplicated isolated mesenteric
      artery dissection outcomes over observation alone.
AB  - OBJECTIVE: Isolated dissection of the mesenteric vessels is rare but increasingly
      recognized. This study aimed to evaluate patient characteristics, primary
      treatment, and subsequent outcomes of mesenteric dissection using multi
      institutional data. METHODS: All patients at participant hospitals between
      January 2003 and December 2015 with dissection of the celiac artery (or its
      branches) or dissection of the superior mesenteric artery (SMA) were included.
      Patients with an aortic dissection were excluded. Demographic, treatment, and
      follow-up data were collected. The primary outcomes included late vessel
      thrombosis (LVT) and aneurysmal degeneration (AD). RESULTS: Twelve institutions
      identified 227 patients (220 with complete treatment records) with a mean age of
      55 +/- 12.5 years. Median time to last follow up was 15 months (interquartile
      range, 3.8-32). Most patients were men (82% vs 18% women) and symptomatic at
      presentation (162 vs 65 asymptomatic). Isolated SMA dissection was more common
      than celiac artery dissection (n = 158 and 81, respectively). Concomitant
      dissection of both arteries was rare (n = 12). The mean dissection length was
      significantly longer in symptomatic patients than in asymptomatic patients in
      both the celiac artery (27 vs 18 mm; P = .01) and the SMA (64 vs 40 mm; P <
      .001). Primary treatment was medical in 146 patients with oral anticoagulation or
      antiplatelet therapy (n = 76 and 70, respectively), whereas 56 patients were
      observed. LVT occurred in six patients, and 16 patients developed AD (3% and 8%,
      respectively). For symptomatic patients without evidence of ischemia (n = 134),
      there was no difference in occurrence of LVT with medical therapy compared with
      observation alone (9% vs 0%; P = .35). No asymptomatic patient (n = 64) had an
      episode of LVT at 5 years. AD rates did not differ among symptomatic patients
      without ischemia treated with medical therapy or observed (9% vs 5%; P = .95).
      Surgical or endovascular intervention was performed in 18 patients (3 ischemia,
      13 pain, 1 AD, 1 asymptomatic). Excluding the patients treated for ischemia,
      there was no difference in LVT with surgical intervention vs medical management
      (one vs five; P = .57). CONCLUSIONS: Asymptomatic patients with isolated
      mesenteric artery dissection may be observed and followed up with intermittent
      imaging. Symptomatic patients tend to have longer dissections than asymptomatic
      patients. Symptomatic isolated mesenteric artery dissection without evidence of
      ischemia does not require anticoagulation and may be treated with antiplatelet
      therapy or observation alone.

PMID- 28506481
TI  - Peri- and intraoperative cognitive and language assessment for surgical resection
      in brain eloquent structures.
AB  - Neuropsychological care of patients suffering from an infiltrative glioma and
      candidates for a neurosurgery under awake condition with intraoperative
      functional mapping is a critical and mandatory stage in therapeutic management.
      It enables to estimate the functional impact of the tumor and, consequently, the
      efficacy of functional reorganization typically observed in these patients, not
      only to better predict surgery outcomes and select appropriate tasks for
      intraoperative functional mapping, but also to plan efficient and individualized
      postoperative cognitive rehabilitation strategies. Neuropsychological care
      management also enables patients to benefit from a solid psychological
      preparation both to the surgery and its associated transitory functional
      consequences, as well as provide a personalized psychological and emotional long
      term support. Based on their solid experience in the peri-operative care of
      diffuse low-grade glioma patients, the authors thoroughly describe the different
      stages of neuropsychological management. Cognitive, emotional and language
      assessments typically used by the authors around and during surgery are reported,
      and different possible avenues of improvement are further discussed.

PMID- 28506480
TI  - The epidemiology of inpatient pediatric trauma in United States hospitals 2000 to
      2011.
AB  - BACKGROUND: This study provides important updates to the epidemiology of
      pediatric trauma in the United States. METHODS: Age-specific epidemiologic
      analysis of the Healthcare Cost and Utilization Project's Nationwide Inpatient
      Sample, representing 2.4 million pediatric traumatic injury discharges in the US
      from 2000 to 2011. We present yearly data with overlying loess smoothing lines,
      proportions of common injuries and surgical procedures, and survey-adjusted
      logistic regression analysis. RESULTS: From 2000 to 2011 there was a 21.7%
      decline in US pediatric trauma injury inpatient discharges from 273.2 to 213.7
      admissions per 100,000. Inpatient case-fatality decreased 5.5% from 1.26% (95% CI
      1.05-1.47) to 1.19% (95% CI 1.01-1.38). Severe injuries accounted for 26.5%
      (se=0.11) of all discharges in 2000 increasing to 31.3% (se=0.13) in 2011. The
      most common injury mechanism across all age groups was motor vehicle crashes
      (MVCs), followed by assaults (15-19years), sports (10-14), falls (5-9) and burns
      (<5). The total injury-related, inflation-adjusted cost was $21.7 billion,
      increasing 56% during the study period. CONCLUSIONS: The overall rate of
      inpatient pediatric injury discharges across the United States has been
      declining. While injury severity is increasing in hospitalized patients, case
      fatality rates are decreasing. MVCs remain a common source of all pediatric
      trauma. LEVELS OF EVIDENCE: Level III.

PMID- 28506482
TI  - Technical principles of direct bipolar electrostimulation for cortical and
      subcortical mapping in awake craniotomy.
AB  - INTRODUCTION: Intraoperative application of electrical current to the brain is a
      standard technique during brain surgery for inferring the function of the
      underlying brain. The purpose of intraoperative functional mapping is to reliably
      identify cortical areas and subcortical pathways involved in eloquent functions,
      especially motor, sensory, language and cognitive functions. MATERIAL AND
      METHODS: The aim of this article is to review the rationale and the
      electrophysiological principles of the use of direct bipolar electrostimulation
      for cortical and subcortical mapping under awake conditions. RESULTS: Direct
      electrical stimulation is a window into the whole functional network that
      sustains a particular function. It is an accurate (spatial resolution of about
      5mm) and a reproducible technique particularly adapted to clinical practice for
      brain resection in eloquent areas. If the procedure is rigorously applied, the
      sensitivity of direct electrical stimulation for the detection of cortical and
      subcortical eloquent areas is nearly 100%. The main disadvantage of this
      technique is its suboptimal specificity. Another limitation is the identification
      of eloquent areas during surgery, which, however, could have been functionally
      compensated postoperatively if removed surgically. CONCLUSION: Direct electrical
      stimulation is an easy, accurate, reliable and safe invasive technique for the
      intraoperative detection of both cortical and subcortical functional brain
      connectivity for clinical purpose. In our opinion, it is the optimal technique
      for minimizing the risk of neurological sequelae when resecting in eloquent brain
      areas.

PMID- 28506483
TI  - Cortical and subcortical functional neuroanatomy for low-grade glioma surgery.
AB  - Knowledge of the encephalon anatomy is crucial for neurosurgical practice,
      especially the main cortical functional structures and their connections. General
      organisation of the encephalon is presented with frontal, parietal, occipital,
      temporal, limbic and insular lobes and their Brodmann correspondence. Secondly,
      subcortical anatomy will be presented with main white matter fasciculi in three
      separated categories: association, commissural and projection fibers. Main
      association fibers are inferior occipitofrontal fasciculus, superior longitudinal
      fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, uncinate
      fasciculus, and cingulum. Commissural fibers include anterior commissure, corpus
      callosum and fornix. Projection fibers are internal capsule and optic radiations.

PMID- 28506484
TI  - A surgical approach to the anatomo-functional structure of language.
AB  - INTRODUCTION: Language is the most widely mapped cognitive function during brain
      surgery. Intraoperative language functional mapping using direct electrical
      stimulation under awake conditions is currently the gold standard technique for
      establishing the causal link between an area and a deficit that would be caused
      by its resection. It is also a powerful tool to investigate the anatomical
      correlates of current neuropsychological models of language. MATERIAL AND
      METHODS: The aim of this article is to reexamine the anatomo-functional structure
      of language that could be inferred from data obtained in direct electrical
      stimulation studies during awake surgery. RESULTS: Concomitantly with the
      development of new neuropsychological models of language, major advances have
      been made in our understanding of error patterns elicited by language network
      stimulation, both cortically and axonally. Following the recognition of visual
      information, the language network of picture naming is organized in parallel into
      two main dorsal phonological and ventral semantic subsystems that are sustained
      anatomically by two systems (arcuate fasciculus and inferior fronto
      occipital/inferior longitudinal/uncinate fasciculus respectively). Networks of
      articulatory and motor aspects of speech are now better depicted (aslant tract,
      third branch of longitudinal fasciculus). Finally, the links between the core
      language networks and the cognitive control networks are also emerging.
      CONCLUSION: Mastering the language map and its dynamical properties should be a
      basic prerequisite for any neurosurgeon who wishes to operate on the brain with
      the aim of optimizing the extent of resection while preserving language
      abilities.

PMID- 28506485
TI  - Surgery for dysembryoplastic neuroepithelial tumors and gangliogliomas in
      eloquent areas. Functional results and seizure control.
AB  - INTRODUCTION: Dysembryoplastic neuroepithelial tumors and gangliogliomas are
      developmental glioneuronal tumors usually revealed by partial epilepsy. High
      epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location,
      and seizure freedom after complete resection are common characteristics of both
      tumors. We report the specificity of surgical management, functional results and
      seizure outcome in cases of a tumor location in eloquent areas. METHODS: Among
      150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a
      glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial
      tumors=21; gangliogliomas=9) had a tumor located in an eloquent cortex (sensory
      motor, insular or language areas). Surgery was performed after a preoperative
      work-up, including stereo-electroencephalography in 48 patients (26%) and
      functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in
      extra-temporal location, whereas an additional corticectomy was performed in a
      temporal location. Tumor microsurgical resections were guided using
      neuronavigation and cortical/subcortical electrical stimulations. Multiple
      stereotactic thermocoagulations were performed in two insular tumors. RESULTS:
      New motor/language deficits related to eloquent areas occurred postoperatively in
      6/30 patients (20%) without any major permanent disability. Minor sensorimotor
      (n=2) and moderate language disturbance (n=1) persisted in three of them.
      Postoperative seizure-free outcome (mean follow-up>5 years) was obtained in 81%
      of the entire series, but significantly decreased to 60% in eloquent areas.
      Incomplete tumor resection was the main cause of surgical failure. However,
      unfavorable seizure outcome was also observed despite complete tumor resection.
      Malignant transformation occurred in one ganglioglioma. CONCLUSION: Epilepsy
      surgery for benign glioneuronal tumors in eloquent areas provides acceptable
      results regarding the functional risks. Complete tumor resection is crucial for
      long-term favorable outcome.

PMID- 28506486
TI  - Preoperative and intraoperative neurophysiological investigations for surgical
      resections in functional areas.
AB  - Brain regions are removed to treat lesions, but great care must be taken not to
      disturb or remove functional areas in the lesion and in surrounding tissue where
      healthy and diseased cells may be intermingled, especially for infiltrating
      tumors. Cortical functional areas and fiber tracts can be localized
      preoperatively by probabilistic anatomical tools, but mapping of functional
      integrity by neurophysiology is essential. Identification of the primary motor
      cortex seems to be more effectively performed with transcranial magnetic
      stimulation (TMS) than functional magnetic resonance imaging (fMRI). Language
      area localization requires auditory evoked potentials or TMS, as well as fMRI and
      diffusion tensor imaging for fiber tracts. Somatosensory cortex is most
      effectively mapped by somatosensory evoked potentials. Crucial eloquent areas,
      such as the central sulcus, primary somatomotor areas, corticospinal tract must
      be defined and for some areas that must be removed, potential compensations may
      be identified. Oncological/functional ratio must be optimized, resecting the
      tumor maximally but also sparingly, as far as possible, the areas that mediate
      indispensable functions. In some cases, a transient postoperative deficit may be
      inevitable. In this article, we review intraoperative exploration of motricity,
      language, somatosensory, visual and vestibular function, calculation, memory and
      components of consciousness.

PMID- 28506487
TI  - A review of monopolar motor mapping and a comprehensive guide to continuous
      dynamic motor mapping for resection of motor eloquent brain tumors.
AB  - Monopolar mapping of motor function differs from the most commonly used method of
      intraoperative mapping, i.e. bipolar direct electrical stimulation at 50-60Hz
      (Penfield technique mapping). Most importantly, the monopolar probe emits a
      radial, homogenous electrical field different to the more focused inter-tip
      bipolar electrical field. Most users combine monopolar stimulation with the short
      train technique, also called high frequency stimulation, or train-of-five
      techniques. It consists of trains of four to nine monopolar rectangular
      electrical pulses of 200-500MUs pulse length with an inter stimulus interval of 2
      4msec. High frequency short train stimulation triggers a time-locked motor-evoked
      potential response, which has a defined latency and an easily quantifiable
      amplitude. In this way, motor thresholds might be used to evaluate a current-to
      distance relation. The homogeneous electrical field and the current-to-distance
      approximation provide the surgeon with an estimate of the remaining distance to
      the corticospinal tract, enabling the surgeon to adjust the speed of resection as
      the corticospinal tract is approached. Furthermore, this stimulation paradigm is
      associated with a lower incidence of intraoperative seizures, allowing continuous
      stimulation. Hence, monopolar mapping is increasingly used as part of a strategy
      of continuous dynamic mapping: ergonomically integrated into the surgeon's tools,
      the monopolar probe reliably provides continuous/uninterrupted feedback on motor
      function. As part of this strategy, motor mapping is not any longer a time
      consuming interruption of resection but rather a radar-like, real-time
      information system on the spatial relationship of the current resection site to
      eloquent motor structures.

PMID- 28506488
TI  - Perioperative functional neuroimaging of gliomas in eloquent brain areas.
AB  - Surgical resection of gliomas involving eloquent brain areas must be maximal in
      order to improve patients' survival, and safe to prevent postoperative
      impairments. Therefore, the precise spatial relationship between the lesion and
      eloquent brain areas needs to be established. Functional magnetic resonance
      imaging and diffusion tensor imaging are robust methods with increasing
      indications in neurosurgery for past decade. The aim of this review article is
      not only to pinpoint the major limitations of these methods in order to avoid
      erroneous conclusions, but also to detail practical aspects associated with the
      main paradigms routinely used in functional magnetic resonance imaging, and to
      discuss recent validation of functional magnetic resonance imaging and diffusion
      tensor imaging results with direct electrical stimulation during awake surgery.

PMID- 28506489
TI  - Enhancement of rotator cuff tendon-bone healing with fibroblast growth factor 2
      impregnated in gelatin hydrogel sheets in a rabbit model.
AB  - BACKGROUND: Application of fibroblast growth factor 2 (FGF-2) may improve the
      healing response after rotator cuff (RC) surgical repair. This study aimed to
      determine whether FGF-2-impregnated gelatin hydrogel sheet (GHS) incorporation
      into the bony trough on the greater tuberosity facilitates healing after RC
      surgical repair in rabbits. METHODS: We assigned 120 adult male Japanese white
      rabbits treated with unilateral surgery for supraspinatus tendon repair into the
      following groups: suture-only group (suture); suture and GHS with phosphate
      buffered saline (carrier); suture and GHS with 3 ug of FGF-2 (F3); and suture and
      GHS with 30 ug of FGF-2 (F30). The effect of FGF-2 was assessed using histologic,
      biomechanical, and microcomputed tomography evaluations at 2, 6, and 12 weeks.
      RESULTS: At 12 weeks, loose fibrovascular tissues emerged at the repair site in
      the suture and carrier groups and dense tendon-like tissues in the F3 and F30
      groups, which demonstrated significantly higher ultimate load-to-failure and
      stress-to-failure at 12 weeks than that in the suture and carrier groups.
      Microcomputed tomography imaging showed ectopic calcification formation in some
      specimens from each group. Appearances or frequencies were similar among groups.
      The histologic and biomechanical effects of FGF-2 on RC healing were obvious at
      >=6 weeks postoperatively. CONCLUSION: FGF-2-impregnated GHS incorporation into
      the bony trough on the greater tuberosity before RC surgical repair is feasible
      and results in histologic and biomechanical improvements during RC healing in
      rabbits. No detrimental effect on ectopic calcification was observed.

PMID- 28506490
TI  - Early range of motion exercise in pediatric patients with olecranon fractures
      treated with tension band suture with double loops and double knots.
AB  - BACKGROUND: Pediatric patients with olecranon fractures are uncommon. The tension
      band suture technique was introduced to reduce the burden of implant removal and
      other complications. However, to our knowledge, early range of motion (ROM)
      exercise has not been introduced in this population of patients. Double Vicryl
      loops and knots with 2 cross-pins are used to maintain the benefits of the
      tension band suture technique and to enhance fixation tensile strength. We
      believe that early ROM exercises could be achieved without nonunion or fixation
      failure. METHODS: Twelve pediatric patients with olecranon fractures were treated
      with tension band suture with double loops and knots between 2004 and 2015.
      Vicryl No. 1 was used for wiring. ROM exercises were initiated 1 week
      postoperatively with a customized functional brace. Early functional outcomes
      were evaluated by the Mayo Elbow Performance Score at every visit after 8 weeks
      postoperatively. RESULTS: Nine boys and 3 girls (average age, 10.6 years; range,
      5 years 7 months-16 years 2 months) were included in the study. Initial
      displacement and angulation of the fractures were 5 mm (2-7 mm) and 12 degrees 
      (4 degrees -25 degrees ), respectively. Two cases had radial neck fractures of
      the ipsilateral elbow. All patients had a perfect Mayo Elbow Performance Score
      after 8 weeks postoperatively. Pin removals were performed at 13.1 weeks. No
      complications, including growth arrest, were observed. DISCUSSION/CONCLUSION:
      Tension band suture with double loops and knots, combined with early ROM
      exercise, may be a complete alternative to tension band wiring.

PMID- 28506492
TI  - Editorial.

PMID- 28506491
TI  - Mapping of glenoid bone loss in recurrent anterior shoulder instability: is there
      a particular deficit pattern?
AB  - BACKGROUND: Glenoid bone loss in recurrent anterior shoulder instability is a
      challenging problem for shoulder surgeons, and knowledge about the anatomy of
      glenoid deficits is scarce. In this study, we tried to evaluate the pattern of
      this pathology. METHODS: Our analysis included 44 shoulders from 44 patients with
      recurrent anterior shoulder instability accompanied by a clinically relevant
      glenoid bone loss. The defect size, the localization of the inferior defect edge,
      and the defect angle were measured, and osseous landmarks were identified. An en
      face view on 2-dimensional computed tomography scans of each patient was fitted
      onto a template to create a deficit map for small (<23%) and large (>23%)
      defects. RESULTS: The study cohort consisted of 9 women and 35 men with a mean
      age of 33 +/- 11 years at the date of the scan. The defect size and localization
      of the inferior defect edge showed significant differences between both groups,
      indicating a more posterior position of larger defects. The defect angle,
      however, showed no significant difference between small and large defects. Both
      groups showed a vertical defect pattern. CONCLUSION: The osseous glenoid deficit
      in recurrent anterior shoulder instability shows a vertical pattern with no
      remarkable differences between small and large defects. This finding can
      influence biomechanical models as well as surgical reconstruction.

PMID- 28506493
TI  - Strategies for investigating the maternal-fetal interface in the first trimester
      of pregnancy: What can we learn about pathology?
AB  - The pathologies of the pregnancy complications pre-eclampsia (PE) and fetal
      growth restriction (FGR) are established in the first trimester of human
      pregnancy. In a normal pregnancy, decidual spiral arteries are transformed into
      wide diameter, non-vasoactive vessels capable of meeting the increased demands of
      the developing fetus for nutrients and oxygen. Disruption of this transformation
      is associated with PE and FGR. Very little is known of how these first trimester
      changes are regulated normally and even less is known about how they are
      compromised in complicated pregnancies. Interactions between maternal and
      placental cells are essential for pregnancy to progress and this review will
      summarise the challenges in investigating this area. We will discuss how first
      trimester studies of pregnancies with an increased risk of developing PE/FGR have
      started to provide valuable information about pregnancy at this most dynamic and
      crucial time. We will discuss where there is scope to progress these studies
      further by refining the ability to identify compromised pregnancies at an early
      stage, by integrating information from many cell types from the same pregnancy,
      and by improving our methods for modelling the maternal-fetal interface in vitro.

PMID- 28506494
TI  - Sociomics: Using Omic Approaches to Understand Social Evolution.
AB  - All of life is social, from genes cooperating to form organisms, to animals
      cooperating to form societies. Omic approaches offer exceptional opportunities to
      solve major outstanding problems in the study of how sociality evolves. First,
      omics can be used to clarify the extent and form of sociality in natural
      populations. This is especially useful in species where it is difficult to study
      social traits in natural populations, such as bacteria and other microbes.
      Second, omics can be used to examine the consequences of sociality for genome
      evolution and gene expression. This is especially useful in cases where there is
      clear variation in the level of sociality, such as the social insects. Major
      tasks for the future are to apply these approaches to a wider range of non-model
      organisms, and to move from exploratory analyses to the testing of evolutionary
      theory.

PMID- 28506495
TI  - Relationship between patient group participation and self-care agency among
      patients with a history of cardiac surgery: A cross-sectional study.
AB  - BACKGROUND: Little is known regarding the influence of participation in patient
      groups on self-care in patients with a cardiac surgery history. OBJECTIVES: To
      investigate the relationship between patient group participation and self-care
      among patients with a cardiac surgery history. METHODS: Participants were 956
      patients with cardiac surgery history from a patient group. Information on self
      care agency, patient group participation, and health status was collected through
      a self-administered questionnaire. RESULTS: There were 566 valid responses.
      Participants were mostly male (76.4%), and the mean age was 70.6 years. A high
      social support level from a patient group was associated with each subscale of
      the self-care agency as follows: self-care operations (odds ratio [OR] 1.08, 95%
      confidence interval [CI] 1.04-1.12), adjusting one's condition (OR 1.04, 95% CI
      1.01-1.07), and attention to self-care (OR 1.05, 95% CI 1.02-1.07). CONCLUSIONS:
      Patient group participation may promote self-care performance in patients with a
      cardiac surgery history.

PMID- 28506496
TI  - Twins labeling-liquid chromatography/mass spectrometry based metabolomics for
      absolute quantification of tryptophan and its key metabolites.
AB  - Tryptophan metabolism plays a crucial role in mediating gastrointestinal
      function. Here, in order to absolutely quantify tryptophan and its metabolites, a
      liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomics
      approach was developed using N-dimethyl-/N-diethyl-amino naphthalene-1-sulfonyl
      chloride (Dns/Dens-Cl) as twins labeling (TL) reagents. Dns-Cl is famous in amine
      and phenol derivations, and structure is similar with Dens-Cl. The introduction
      of easily protonated moiety of tertiary ammonium-containing part in the
      derivatives from Dns to tryptophan and its metabolites not only improved the LC
      separation but also enhanced their MS response. In addition, the Dens labeled
      standards were used as internal standards to compensate for matrix effects and
      ensure accurate quantifications. With the proposed method, twelve metabolites in
      tryptophan pathway could be detected at sub-ng/mL levels using only 20MUL rat
      serum (the limit of detection could reach 3pg/mL for tryptamine, N-acetyl
      serotonin and 6-hydroxymelatonin). The sensitivity was enhanced about 1-2 orders
      of magnitude compared with non-derivatization method. Focusing on tryptophan
      pathway, the method was successfully applied to determine the absolute serum
      concentrations of twelve tryptophan metabolites in a vincristine-induced ileus
      rat model. A significant down-regulation of the tryptophan metabolism along the
      kynurenine pathway and up-regulation of serotonin pathway were uncovered. Our
      findings provide a deeper insight into the mechanism of gastrointestinal
      dysfunction.

PMID- 28506497
TI  - Comparison of enzymatic hydrolysis in a centrifugal partition chromatograph and
      stirred tank reactor.
AB  - Recently the Centrifugal Partition Chromatography (CPC) device is investigated as
      a reactor for biocatalytic reactions, as it enables biocatalyst immobilization
      without solid support and continuous operation of biphasic reaction systems.
      However, a detailed determination of the enzymes behavior in the CPC reactor and
      comparison to a classical stirred tank reactor (STR) for biphasic enzyme
      catalysis is not shown yet. In this study, the performance of an enzymatic
      biphasic hydrolysis reaction using lipase from Candida rugosa is systematically
      evaluated using a STR. The results are compared to different experiments
      conducted in the CPC reactor and used to evaluate the reaction performance in
      each. The same characteristics and limitations were observed in STR and CPC. At
      all states the CPC provided a similar reaction performance. However, the reaction
      in the CPC runs faster into limitations and was not easily scalable due to
      complex effects of the flow pattern. Although the enzyme was immobilized
      successfully and the activity of the lipase was preserved during CPC operation
      optimizations are needed to make the CPC reactor more competitive. For instance,
      scaling up the chamber geometry seems to be mandatory to increase the reaction
      performance, which may promote this reactor concept as an alternative to common
      devices for continuous biphasic biocatalytic reactions.

PMID- 28506499
TI  - Determination of butyltins, phenyltins and octyltins in foods with preservation
      of their moieties: A critical review on analytical methods.
AB  - Tributyltin and triphenyltin have been extensively applied in anti-fouling paints
      since the 1960s. Hence, organotin compounds (OTCs), especially butyltins and
      phenyltins, in seafood has been of concern for decades. Even though the
      "International Convention on the Control of Harmful Anti-Fouling Systems on
      Ships, 2001" entered into force internationally in 2008 and prohibited the use of
      OTCs in anti-fouling paints used on ships, the analysis of OTCs in seafood was
      not commonly included in routine monitoring programmes. Besides, species of
      triphenyltin, including triphenyltin hydroxide and acetate, have been used as
      pesticides and may accumulate in food. Moreover, the European Food Safety Agency
      established a group tolerable daily intake for tributyltin, dibutyltin,
      triphenyltin and dioctyltin in 2004 as they exert their immunotoxic effects by
      similar mode of action and potency. Therefore, suitable methods are needed to
      analyze butyl-, phenyl- and octyl-tins simultaneously in food without affecting
      their moieties. This review aims to provide background information in this area.

PMID- 28506498
TI  - Sweet spot matching: A thin-layer chromatography-based countercurrent solvent
      system selection strategy.
AB  - TLC-based strategies were proposed in 1979 (Hostettmann et al.) and 2005 (Friesen
      & Pauli; GUESS method) to minimize the number of partitioning experiments
      required for countercurrent separation (CCS) solvent system selection. As semi
      empirical approaches, both proposed that the K values defining the sweet spot of
      optimal CCS corresponded to a matching Rf value range from the silica gel TLC
      plate developed in the organic phase of a biphasic or a corresponding monophasic
      solvent system. Despite their simplicity, there has been an absence of
      theoretical support and a deficiency of reported experimental evidence. The
      present study explores the theory required to develop correlations between Rf and
      K. All theoretical models surmise that the optimal Rf value range should be
      centered at 0.5. In order to validate the feasibility of the concept of matching
      Rf and K values, 43 natural products and six solvent system families were
      investigated. Out of 62 correlations, 45 resulted in matched Rf and K values.
      Based on this study, practical guidelines for the TLC-based prediction strategy
      are provided. These approaches will equip CCS users with an updated understanding
      of how to apply the TLC-based solvent system selection strategy to accelerate a
      targeted selection of CCS conditions.

PMID- 28506501
TI  - Sympathetic control of the brain circulation: Appreciating the complexities to
      better understand the controversy.
AB  - Although the human cerebral circulation is richly innervated with sympathetic
      nerve fibers, the role of sympathetic nerve activity (SNA) on the regulation of
      cerebral blood flow (CBF) remains debated. Several issues may be responsible for
      the conflicting conclusions reported in the animal vs. human literature in
      regards to the sympathetic control of the brain circulation. Furthermore, due to
      the physiological consequences associated with SNA blockade (e.g. changes in
      blood pressure and cardiac output), and differences in methodology (e.g.
      assessment of CBF), interpretation of the role of SNA in CBF regulation in humans
      is challenging. The goals of this brief review are to provide an overview of the
      role of neural control in the regulation of CBF, with a focus on SNA and discuss
      the likely reasons behind the controversial influence of SNA on CBF regulation. A
      final objective of this article is to critically review the various methods
      available to measure CBF and highlight their strengths and weaknesses to provide
      insight in SNA regulation of CBF.

PMID- 28506500
TI  - Autonomic and electrocardiographic findings in Parkinson's disease.
AB  - Parkinson disease (PD) is a progressive neurodegenerative disorder characterized
      by motor and non-motor symptoms and signs. Many reports suggest that diminished
      heart rate variability occurs early, even prior to the cardinal signs of PD. In a
      longitudinal study of PD, we evaluated whether heart rate variability (HRV)
      obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval
      would be associated with PD severity and progression. Subjects were derived from
      a longitudinal study of 1741 individuals with early, stable PD. The severity of
      PD was measured using the global statistical test (GST). In a subset, the heart
      rate corrected QT-interval (QTcB) was calculated for each electrocardiogram
      (ECG). The HRV was measured for each ECG and then transformed to fit a normal
      distribution. The baseline analysis included 653 subjects, with 256 completing
      the 5-year follow up study. There was an association (P<0.05) between QTcB and PD
      severity in individuals that were taking QT-interval affecting drugs. A longer QT
      interval at baseline was associated with more advanced PD at 5years (P<0.05), and
      greater disease progression over 5years (P<0.05). There was an association
      between diminished HRV and an orthostatic decrease in standing blood pressure at
      baseline in individuals with PD (P<0.05). HRV was not associated with PD severity
      or progression. In conclusion, we were able to detect measurable associations
      between the QTcB interval and PD severity, PD severity 5years later, and the
      change in disease over time. However, routine ECG tracings appear inadequate for
      the evaluation of autonomic function in PD.

PMID- 28506503
TI  - Extended Clinical Spectrum of Anti-N-Methyl-d-Aspartate Receptor Encephalitis in
      Children: A Case Series.
AB  - OBJECTIVE: There is a wide spectrum of clinical manifestations in children with
      anti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis from two
      different health care settings. METHODS: We describe our experience with 13
      patients (median age, 7 years; range, 5 months to 19 years) presenting to
      tertiary referral centers in India and the United States. RESULTS: Initial
      manifestations were neurological (seizures or movement disorders) in eight
      patients, and psychiatric (e.g., emotional lability and hallucination) in five
      patients. Symptoms during the clinical course included seizures in ten patients,
      movement disorders (dyskinesia and choreiform movements) in 11 patients, and
      behavioral changes (aggressiveness and insomnia) in ten patients. Concomitant
      infections (herpes simplex virus 1, tuberculous meningitis, and influenza A) were
      present in three patients. Analysis of the cerebrospinal fluid in all except two
      cases preceded by infection (herpes simplex virus encephalitis and tuberculous
      meningitis) was unremarkable. Treatment included intravenous
      immunoglobulin/methylprednisolone (11 patients), rituximab (eight patients),
      plasmapheresis (two patients), and cyclophosphamide (two patients). Six patients
      recovered completely. Two patients had mild residual neurological deficits,
      whereas four had severe residual neurological deficits. Two patients had profound
      autonomic instability, which was the cause of death for one of them. Two patients
      relapsed at two and six months after the initial recovery. CONCLUSIONS: We
      describe the differences and similarities of clinical presentation, test results,
      and response to treatment of children with anti-N-methyl-d-aspartate receptor
      encephalitis from India and the United States. Included is a description of one
      of the youngest patients with anti-N-methyl-d-aspartate receptor encephalitis
      (five months) and the first patient to be reported in association with
      tuberculous meningitis.

PMID- 28506504
TI  - Anti-N-Methyl-d-Aspartate Receptor Encephalitis Appearing as a New-Onset
      Psychosis: Disease Course in Children and Adolescents Within the California
      Encephalitis Project.
AB  - BACKGROUND: Given that psychiatric symptoms are common, not only during the
      course of the illness but also on presentation, in children and adolescents with
      anti-N-methyl-d-aspartate receptor encephalitis, it is important that
      practitioners possess an adequate understanding of the clinical features and
      potential treatment of this disease. We describe the clinical characteristics of
      24 patients who presented to the California Encephalitis Project. METHODS:
      Patients were referred by physicians, and standardized forms were used to gather
      demographic, clinical, and laboratory data. RESULTS: Twenty-four patients between
      ages two and 18 years were identified. Psychosis was a primary presenting symptom
      in two thirds of patients, and just over 20% of these were admitted to an
      inpatient psychiatric facility. Ultimately, all patients developed psychiatric
      symptoms during the course of the illness. There was a characteristic progression
      of symptoms that was consistent with that noted in other studies, with prominent
      psychiatric symptoms initially, which then progressed to seizures and autonomic
      instability in most patients. All of those examined developed movement
      abnormalities, which included primarily orofacial dyskinesias and choreiform
      movements. CONCLUSIONS: Anti-N-methyl-d-aspartate receptor encephalitis, unlike
      other paraneoplastic or autoimmune encephalitides, affects those 18 years and
      under an estimated 40% of the time based on prior studies. Recognizing the signs
      and symptoms of this condition is essential to making a diagnosis and initiating
      timely treatment. Child psychiatrists have an important role in this disorder.

PMID- 28506505
TI  - The Utility of Surveillance Electroencephalography to Guide Early Antiepileptic
      Drug Therapy in Infants With Tuberous Sclerosis Complex.
AB  - BACKGROUND: Seizures are a common early presentation in infants with tuberous
      sclerosis complex (TSC) and can be preceded by electrographic changes on
      electroencephalography (EEG) before clinical seizure onset. A limited number of
      studies have addressed the initial EEG findings in TSC and the outcome of early
      treatment with antiepileptic medication prior to clinical seizure onset. METHODS:
      We describe two infants with tuberous sclerosis complex whose surveillance EEG
      showed focal seizures that were not previously recognized by caregivers. We
      review previously reported patients with TSC with early EEG findings. Our
      patients were started on vigabatrin after the onset of focal seizures with the
      aim of preventing seizure recurrence, halting the possible progression to
      infantile spasms or focal seizures, and preventing neurodevelopmental decline.
      RESULTS: Both patients remain seizure free and have reached appropriate
      developmental milestones. CONCLUSIONS: We recommend early serial EEG monitoring
      once a diagnosis of TSC is suspected or confirmed in infants. Additional
      prospective studies are needed to assess the long-term outcome of early
      antiepileptic drug initiation as soon as electrographic seizure activity is
      detected.

PMID- 28506502
TI  - Autonomic dysreflexia after spinal cord injury: Systemic pathophysiology and
      methods of management.
AB  - Traumatic spinal cord injury (SCI) has widespread physiological effects beyond
      the disruption of sensory and motor function, notably the loss of normal
      autonomic and cardiovascular control. Injury at or above the sixth thoracic
      spinal cord segment segregates critical spinal sympathetic neurons from
      supraspinal modulation which can result in a syndrome known as autonomic
      dysreflexia (AD). AD is defined as episodic hypertension and concomitant
      baroreflex-mediated bradycardia initiated by unmodulated sympathetic reflexes in
      the decentralized cord. This condition is often triggered by noxious yet
      unperceived visceral or somatic stimuli below the injury level and if severe
      enough can require immediate medical attention. Herein, we review the
      pathophysiological mechanisms germane to the development of AD, including
      maladaptive plasticity of neural circuits mediating abnormal sympathetic reflexes
      and hypersensitization of peripheral vasculature that collectively contribute to
      abnormal hemodynamics after SCI. Further, we discuss the systemic effects of
      recurrent AD and pharmacological treatments used to manage such episodes.
      Contemporary research avenues are then presented to better understand the
      relative contributions of underlying mechanisms and to elucidate the effects of
      recurring AD on cardiovascular and immune functions for developing more targeted
      and effective treatments to attenuate the development of this insidious syndrome
      following high-level SCI.

PMID- 28506506
TI  - Endovascular rewarming in the emergency department for moderate to severe
      accidental hypothermia.
AB  - BACKGROUND: Endovascular temperature control catheters can be utilized for
      emergent rewarming in accidental hypothermia. The purpose of this study was to
      compare patients with moderate to severe hypothermia rewarmed with an
      endovascular temperature control catheter versus usual care at our institution.
      METHODS: We conducted a retrospective, observational cohort study of patients
      with moderate to severe accidental hypothermia (core body temperature less than
      32 degrees C) in the Emergency Department of an urban, tertiary care medical
      center. We identified the rewarming techniques utilized for each patient,
      including those who had an endovascular temperature control catheter placed
      (Quattro(c) or Icy(c) catheter, CoolGuard(c) 3000 regulation system, Zoll
      Medical). Rewarming rates and outcomes were compared for patients with and
      without the endovascular temperature control catheter. We systematically screened
      for procedural complications. RESULTS: There were 106 patients identified with an
      initial core temperature less than or equal to 32 degrees C; 52 (49%) patients
      rewarmed with an endovascular temperature control catheter. Other methods of
      rewarming included external forced-air rewarming (85, 80%), bladder lavage (17,
      16%), gastric lavage (10, 9%), closed pleural lavage (6, 6%), and peritoneal
      lavage (3, 3%). Rate of rewarming did not differ between the groups with and
      without catheter-based rewarming (1.3 degrees C/h versus 1.0 degrees C/h,
      difference 0.3 degrees C, 95% confidence interval [CI] of the difference 0-0.6
      degrees C) and neither did survival (70% versus 71%, difference 1%, 95% CI -17 to
      20%). We did not identify any significant vascular injuries resulting from
      endovascular catheter use. CONCLUSION: The endovascular temperature control
      system was not associated with an increased rate of rewarming in this cohort with
      moderate to severe hypothermia; however, this technique appears to be safe and
      feasible.

PMID- 28506507
TI  - Syndrome surveillance of fentanyl-laced heroin outbreaks: Utilization of EMS,
      Medical Examiner and Poison Center databases.
AB  - OBJECTIVE: Describe surveillance data from three existing surveillance systems
      during an unexpected fentanyl outbreak in a large metropolitan area. METHODS: We
      performed a retrospective analysis of three data sets: Chicago Fire Department
      EMS, Cook County Medical Examiner, and Illinois Poison Center. Each included data
      from January 1, 2015 through December 31, 2015. EMS data included all EMS
      responses in Chicago, Illinois, for suspected opioid overdose in which naloxone
      was administered and EMS personnel documented other criteria indicative of opioid
      overdose. Medical Examiner data included all deaths in Cook County, Illinois,
      related to heroin, fentanyl or both. Illinois Poison Center data included all
      calls in Chicago, Illinois, related to fentanyl, heroin, and other prescription
      opioids. Descriptive statistics using Microsoft Excel(r) were used to analyze the
      data and create figures. RESULTS: We identified a spike in opioid-related EMS
      responses during an 11-day period from September 30-October 10, 2015. Medical
      Examiner data showed an increase in both fentanyl and mixed fentanyl/heroin
      related deaths during the months of September and October, 2015 (375% and 550%
      above the median, respectively.) Illinois Poison Center data showed no
      significant increase in heroin, fentanyl, or other opioid-related calls during
      September and October 2015. CONCLUSION: Our data suggests that EMS data is an
      effective real-time surveillance mechanism for changes in the rate of opioid
      overdoses. Medical Examiner's data was found to be valuable for confirmation of
      EMS surveillance data and identification of specific intoxicants. Poison Center
      data did not correlate with EMS or Medical Examiner data.

PMID- 28506508
TI  - The influence of substance misuse on clinical outcomes following burn.
AB  - INTRODUCTION: Ongoing increases in the prevalence of substance misuse among burn
      injured patients necessitate a contemporary analysis of the association between
      substance misuse and clinical outcomes in burn-injured adults. METHODS: We
      conducted a retrospective cohort study of 1199 patients admitted to a regional
      burn center. History of substance misuse was derived from a prospective clinical
      registry and categorized as alcohol, illicit drug, or both. The primary outcome
      was hospital length of stay; association of substance misuse and inpatient
      complications were secondary outcomes. Multivariable logistic regression was used
      to model the association between categories of substance misuse and each outcome,
      adjusting for patient and injury characteristics. RESULTS: The incidence of
      substance misuse was 34% overall. After adjustment for patient and injury
      characteristics, drug misuse was associated with a significantly longer length of
      stay (RR 1.12; 95% CI 1.00-1.25), as was alcohol misuse (RR 1.32; 95% CI 1.14
      1.52), and drug/alcohol misuse (RR 1.34; 95% CI 1.16-1.56). Drug/alcohol misuse
      was associated with significantly higher rates of bacteremia (OR 3.84; 95% CI
      1.83-8.04) and sepsis (OR 2.50; CI 1.13-5.53). CONCLUSIONS: A history of
      substance misuse is associated with an increased risk of inpatient complications
      and longer hospital stay. Providers should be cognizant of increased
      complications in this cohort with a view to improving outcomes.

PMID- 28506509
TI  - Sub fascial flap based on the supraclavicular artery in reconstruction of neck
      burn contractures.
AB  - This study presents 3 cases of women ages ranged from 25 to 52 years with
      anterior cervical contractures caused by burns that resulted in functional and
      aesthetic deficit. Contracture release in 3 patients and reconstruction was done
      using a sub-fascial flap whose main pedicle was the supraclavicular artery and
      the occipito-postero-cervical vessels that were preserved. The flap was designed
      differently from the classically described that uses the skin of the shoulder but
      which presents differences of color and texture with relation to the skin of the
      neck. The results were satisfactory and no complications such as infections or
      necrosis.

PMID- 28506510
TI  - Can Occult Invasive Disease in Ductal Carcinoma In Situ Be Predicted Using
      Computer-extracted Mammographic Features?
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine whether mammographic
      features assessed by radiologists and using computer algorithms are prognostic of
      occult invasive disease for patients showing ductal carcinoma in situ (DCIS) only
      in core biopsy. MATERIALS AND METHODS: In this retrospective study, we analyzed
      data from 99 subjects with DCIS (74 pure DCIS, 25 DCIS with occult invasion). We
      developed a computer-vision algorithm capable of extracting 113 features from
      magnification views in mammograms and combining these features to predict whether
      a DCIS case will be upstaged to invasive cancer at the time of definitive
      surgery. In comparison, we also built predictive models based on physician
      interpreted features, which included histologic features extracted from biopsy
      reports and Breast Imaging Reporting and Data System-related mammographic
      features assessed by two radiologists. The generalization performance was
      assessed using leave-one-out cross validation with the receiver operating
      characteristic curve analysis. RESULTS: Using the computer-extracted mammographic
      features, the multivariate classifier was able to distinguish DCIS with occult
      invasion from pure DCIS, with an area under the curve for receiver operating
      characteristic equal to 0.70 (95% confidence interval: 0.59-0.81). The physician
      interpreted features including histologic features and Breast Imaging Reporting
      and Data System-related mammographic features assessed by two radiologists showed
      mixed results, and only one radiologist's subjective assessment was predictive,
      with an area under the curve for receiver operating characteristic equal to 0.68
      (95% confidence interval: 0.57-0.81). CONCLUSIONS: Predicting upstaging for DCIS
      based upon mammograms is challenging, and there exists significant interobserver
      variability among radiologists. However, the proposed computer-extracted
      mammographic features are promising for the prediction of occult invasion in
      DCIS.

PMID- 28506511
TI  - An Abbreviated Protocol for High-risk Screening Breast Magnetic Resonance
      Imaging: Impact on Performance Metrics and BI-RADS Assessment.
AB  - RATIONALE AND OBJECTIVES: Annual breast magnetic resonance imaging (MRI) is
      recommended to screen high-risk populations for breast cancer, although costs are
      significant. This study assesses the performance of an abbreviated MRI protocol
      as a resource-efficient approach for screening patients at high-risk of breast
      cancer, and assesses whether the abbreviated protocol alters the assigned Breast
      Imaging Reporting and Data System (BI-RADS) category. MATERIALS AND METHODS: This
      is a prospective paired cohort study performed in an academic ambulatory setting.
      MRI images of women at high risk of breast cancer were reviewed using an
      abbreviated MRI protocol, followed by an immediate review of additional sequences
      included in a full diagnostic protocol. BI-RADS assessments, including all
      changes and interpretation times, were recorded for both the abbreviated and full
      protocol reviews. Cancer detection rate, positive predictive value 3 (PPV3),
      sensitivity, and specificity were calculated. RESULTS: A total of 1052 MRI cases
      were reviewed. The cancer detection rate was 13.3 per 1000 with a PPV3 of 30.4%
      based on the full protocol. Review of sequences included in the full protocol
      resulted in a change in the final BI-RADS assessments in 3.4% of the cases, the
      majority of which did not change clinical management with respect to biopsy. The
      sensitivity and specificity of the abbreviated and full protocols were not
      significantly different. CONCLUSIONS: This pilot study of an abbreviated MRI
      protocol demonstrates effective performance in cancer detection. BI-RADS
      assessments were rarely altered with the additional information afforded by the
      full protocol. The abbreviated protocol holds promise for resource-efficient
      breast cancer screening in high-risk women.

PMID- 28506512
TI  - Clinical Workflow Can Threaten Resident Education.

PMID- 28506513
TI  - Letter to the Editor: Use of Publicly Available Image Resources.

PMID- 28506514
TI  - A Novel Cooling Method and Comparison of Active Rewarming of Mildly Hypothermic
      Subjects.
AB  - OBJECTIVE: To compare the effectiveness of arteriovenous anastomosis (AVA) vs
      heated intravenous fluid (IVF) rewarming in hypothermic subjects. Additionally,
      we sought to develop a novel method of hypothermia induction. METHODS: Eight
      subjects underwent 3 cooling trials each to a core temperature of 34.8+/-0.6
      (32.7 to 36.3 degrees C [mean+/-SD with range]) by 14 degrees C water immersion
      for 30 minutes, followed by walking on a treadmill for 5 minutes. Core
      temperatures (Deltates) and rates of cooling ( degrees C/h) were measured.
      Participants were then rewarmed by 1) control: shivering only in a sleeping bag;
      2) IVF: shivering in sleeping bag and infusion of 2 L normal saline warmed to 42
      degrees C at 77 mL/min; and 3) AVA: shivering in sleeping bag and circulation of
      45 degrees C warmed fluid through neoprene pads affixed to the palms and soles of
      the feet. RESULTS: Cold water immersion resulted in a decrease of 0.5+/-0.5
      degrees C Deltates and 1+/-0.3 degrees C with exercise (P < .01); with an
      immersion cooling rate of 0.9+/-0.8 degrees C/h vs 12.6+/-3.2 degrees C/h with
      exercise (P < .001). Temperature nadir reached 35.0+/-0.5 degrees C. There were
      no significant differences in rewarming rates between the 3 conditions
      (shivering: 1.3+/-0.7 degrees C/h, R2 = 0.683; IVF 1.3+/-0.7 degrees C/h, R2 =
      0.863; and AVA 1.4+/-0.6 degrees C/h, R2 = 0.853; P = .58). Shivering inhibition
      was greater with AVA but was not significantly different (P = .07). CONCLUSIONS:
      This study developed a novel and efficient model of hypothermia induction through
      exercise-induced convective afterdrop. Although there was not a clear benefit in
      either of the 2 active rewarming methods, AVA rewarming showed a nonsignificant
      trend toward greater shivering inhibition, which may be optimized by an improved
      interface.

PMID- 28506515
TI  - Combined semi-empirical screening and design of experiments (DOE) approach to
      identify candidate formulations of a lyophilized live attenuated tetravalent
      viral vaccine candidate.
AB  - A combination experimental approach, utilizing semi-empirical excipient screening
      followed by statistical modeling using design of experiments (DOE), was
      undertaken to identify stabilizing candidate formulations for a lyophilized live
      attenuated Flavivirus vaccine candidate. Various potential pharmaceutical
      compounds used in either marketed or investigative live attenuated viral vaccine
      formulations were first identified. The ability of additives from different
      categories of excipients, either alone or in combination, were then evaluated for
      their ability to stabilize virus against freeze-thaw, freeze-drying, and
      accelerated storage (25 degrees C) stresses by measuring infectious virus titer.
      An exploratory data analysis and predictive DOE modeling approach was
      subsequently undertaken to gain a better understanding of the interplay between
      the key excipients and stability of virus as well as to determine which
      combinations were interacting to improve virus stability. The lead excipient
      combinations were identified and tested for stabilizing effects using a
      tetravalent mixture of viruses in accelerated and real time (2-8 degrees C)
      stability studies. This work demonstrates the utility of combining semi-empirical
      excipient screening and DOE experimental design strategies in the formulation
      development of lyophilized live attenuated viral vaccine candidates.

PMID- 28506516
TI  - Waning protection following 5 doses of a 3-component diphtheria, tetanus, and
      acellular pertussis vaccine.
AB  - BACKGROUND: The effectiveness of diphtheria, tetanus, and acellular pertussis
      (DTaP) vaccines wanes substantially after the 5th dose given at ages 4-6years,
      but has not been described following 5 doses of the same type of DTaP vaccine. We
      investigated waning effectiveness against pertussis in California over nearly
      10years, which included large pertussis outbreaks, following 5 doses of GSK DTaP
      vaccines (DTaP3). METHODS: We conducted a case-control study (NCT02447978) of
      children who received 5 doses of DTaP at Kaiser Permanente Northern California
      from 01/2006 through 03/2015. We compared time since the 5th dose in confirmed
      pertussis polymerase chain reaction (PCR)-positive cases with pertussis PCR
      negative controls. We used logistic regression adjusted for calendar time, age,
      sex, race, and service area to estimate the effect of time since the 5th DTaP
      dose on the odds of pertussis. Our primary analysis evaluated waning after 5
      doses of DTaP3. We also examined waning after 5 doses of any type of DTaP
      vaccines. RESULTS: Our primary analysis compared 340 pertussis cases diagnosed at
      ages 4-12years with 3841 controls. The any DTaP analysis compared 462 pertussis
      cases with 5649 controls. The majority of all DTaP doses in the study population
      were DTaP3 (86.8%). Children who were more remote from their 5th dose were less
      protected than were children whose 5th dose was more recent; the adjusted odds of
      pertussis increased by 1.27 per year (95% CI 1.10, 1.46) after 5 doses of DTaP3
      and by 1.30 per year (95% CI 1.15, 1.46) after any 5 DTaP vaccines doses.
      CONCLUSIONS: Waning protection after DTaP3 was similar to that following 5 doses
      of any type of DTaP vaccines. This finding is not unexpected as most of the DTaP
      vaccines administered were DTaP3. Following 5 doses of DTaP3 vaccines, protection
      from pertussis waned 27% per year on average. NCT number: NCT02447978.

PMID- 28506517
TI  - Fish oil supplementation benefits the murine host during the acute phase of a
      parasitic infection from Trypanosoma cruzi.
AB  - Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are known to
      modulate a variety of immune cell functions. On occasion, this has led to
      diminished host resistance to certain viral and bacterial infections. Little is
      known about the impact of n-3 PUFA on host resistance to parasitic infection,
      however, based on results from a small study conducted more than two decades ago,
      we hypothesized that providing mice LC n-3 PUFA will diminish host resistance to
      Trypanosoma cruzi, the parasitic pathogen responsible for Chagas disease. To
      investigate this, C57BL/6 mice were supplemented by gavage (0.6% v/w) with
      phosphate-buffered saline, corn oil (CO), or menhaden fish oil (FO, a fat source
      rich in LC n-3 PUFA) for 15 days prior to T cruzi (Y strain) challenge and
      throughout the acute phase of infection. FO supplementation was associated with a
      transient 2-fold greater peak of blood parasitemia at 7 days postinfection (dpi),
      whereas subsequent cardiac parasitemia was ~60% lower at 12 dpi. FO treatment
      also ameliorated the leukopenia and thrombocytopenia observed in the early stages
      of a T cruzi infection. FO supplementation reduced circulating and cardiac nitric
      oxide at 7 and 12 dpi, respectively. FO supplementation altered ex vivo
      prostaglandin E2 and cytokine and chemokine production by splenocytes isolated
      from uninfected and infected mice. Overall, our results suggest that oral
      administration of LC n-3 PUFA from FO can have beneficial effects on the host in
      the early course of a T cruzi infection.

PMID- 28506518
TI  - The addition of peanuts to habitual diets is associated with lower consumption of
      savory non-core snacks by men and sweet non-core snacks by women.
AB  - Snacking is associated with intakes of non-core foods which may predispose to
      obesity. Peanuts have potential satiety benefits and may assist with weight
      management; we hypothesized that peanut consumption would reduce intake of non
      core snack foods due to compensation. We investigated the effects of adding
      peanuts to a habitual diet on snacking habits and energy intake. Sixty-one
      healthy participants (65+/-7years, body mass index 31+/-4kg/m2) consumed their
      habitual diet with or without peanuts (56g/d for 32 women, 84g/d for 29 men) for
      12weeks each in a randomized crossover design. Food diaries were analyzed at
      baseline and after each 12-week period for meal and snack content and timing.
      Total energy intake was higher (17% for men [P<.001], 9% for women [P<.001])
      during the peanut phase. Body weight was 0.5+/-0.2kg (P=.010) greater during the
      peanut phase. Snacking occasions increased during the peanut phase (53% for men
      [P=.001], 14% for women [P=.01]). Servings of other snack foods did not change
      during the peanut phase (P=.6) compared with control. However, sex-specific
      analysis revealed that men and women consumed less savory (P<.001) and sweet
      (P=.01) non-core snacks, respectively, during the peanut phase. Despite increased
      energy intake and snacking frequency, peanuts may improve the diet through sex
      specific reductions of non-core foods; for optimal energy balance, peanuts should
      be substituted rather than added to the diet.

PMID- 28506519
TI  - Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology.
AB  - Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human
      kidney, where it executes reabsorption of filtered glucose with a high capacity;
      it may be overactive in patients with diabetes, especially in the early,
      hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been
      successfully engaged by orally active, selective agents. Initially developed as
      antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo
      actions. Consequences of their primary effect, i.e., profuse glycosuria and
      natriuresis, involve hemodynamic (plasma volume and blood pressure reduction) and
      metabolic pathways (increase in lipid oxidation and ketogenesis at the expense of
      carbohydrate utilization); the hormonal mediation extends to insulin, glucagon,
      and gastrointestinal peptides. Their initial trial in high-risk patients with
      diabetes has provided evidence for marked reduction of cardiovascular risk. This
      review focuses on the quantitative pharmacology of SGLT2 inhibitors, which can be
      exploited to discover new physiology, in the heart, kidney, and brain.

PMID- 28506520
TI  - The Evolving Role of Proton Beam Therapy for Sarcomas.
AB  - As an alternative to conventional photon-based radiotherapy, radiation with
      protons is recognised to offer considerable advantages. Today, central nervous
      system tumours, various sarcomatous tumours, childhood cancer and head and neck
      tumours are commonly treated with proton therapy. This review evaluates current
      data from clinical and dosimetric trials on the treatment of selected sarcomatous
      tumours like rhabdomyosarcoma, osteosarcoma, chordoma, chondrosarcoma and Ewing
      sarcoma. Special considerations for paediatric tumours and future prospects of
      proton therapy are outlined. Proton therapy is already an internal part in the
      multidisciplinary management of childhood sarcomas in contiguity to sensitive
      structures, especially at the base of skull, spine and pelvis. It offers special
      advantages for tumours requiring high-precision radiotherapy, particularly when
      total resection seems not feasible. Previous and ongoing research is generating
      evidence for the benefit of protons in sarcoma patients. Up to now, proton
      therapy has been safely applied with encouraging results. For future research,
      prospective, multi-institutional, large registries are required to answer open
      questions. Modern radiotherapy techniques, such as pencil beam scanning and
      intensity modulation are increasingly established in proton therapy. More
      research is needed to understand protons' limitations and potential.

PMID- 28506521
TI  - Role of Imaging in Response Assessment and Individualised Treatment for Sarcomas.
AB  - The first systematic response evaluation criteria were established by WHO, based
      on the tumor size changes shortly after the computed tomography (CT) technique
      became available to the daily practice. RECIST, a simplified version of WHO
      criteria, and its newer version, RECIST1.1 are the currently available
      international response evaluation criteria in solid tumors and remains based on
      tumor size changes. While the introduction of molecularly targeted drugs has
      significantly improved the survival in patient with sarcomas, the evaluation of
      tumor response has become more complicated. Increasing number of studies have
      reported the lack of shrinkage in responding tumors and raised concerns of
      significant underestimation of responses using RECIST. The first such observation
      was made on gastrointestinal stromal tumor (GIST) treated with imatinib. In GISTs
      responding to imatinib, the degree of contrast enhancement on CT typically
      decreases significantly compared with the baseline, and, regardless of whether
      tumors shrink, heterogeneous hyperattenuating tumors become homogeneous
      hypoattenuating tumors with a smaller enhancing solid component. In current
      oncology practice, CT is a widely accepted method of evaluating tumor response.
      CT images are relatively simple to acquire and can be reasonably reproduced with
      no significant technical obstacles. FDG-PET is highly sensitive and specific in
      identifying responding sarcomas. It has mostly been used as a problem solver and
      for those with marginally resectable GIST. More recently, the utility of whole
      body MRI is undergoing exploration. This article discusses the traditional size
      based response evaluation criteria, and introduces new evidence based response
      evaluation based on changes in morphology in addition to changes in tumor size on
      CT images, and whole body imaging is introduced at the end.

PMID- 28506522
TI  - Thick tumor capsule is a valuable risk factor for distant metastasis in
      follicular thyroid carcinoma.
AB  - OBJECTIVE: While the biological behavior of follicular thyroid carcinoma (FTC)
      has been studied in great detail using clinical experience, few studies have
      investigated pre- or intraoperative factors related to the risk of distant
      metastasis (DM) among patients with FTC. The aim of this study was to analyze the
      characteristics of FTC with DM. METHODS: This study retrospectively investigated
      102 patients with FTC who underwent surgery between 1988 and 2013. We compared
      clinicopathological characteristics between FTC with and without DM. RESULTS:
      Univariate analysis revealed nodal metastasis (p=0.045), serum thyroglobulin (Tg)
      at initial operation (>=1000ng/ml; p<0.0001), widely invasive appearance
      according to macroscopic findings (p<0.0001), thick tumor capsule (>=1mm;
      p<0.0001), vascular invasion (p=0.0003), extrathyroidal invasion (p=0.047), and
      venous tumor embolism (p=0.045) as significant risk factors for DM. Multivariate
      analysis conducted using pre- and intraoperative factors identified thick tumor
      capsule (>=1mm), serum Tg at initial operation (>=1000ng/ml), and macroscopically
      widely invasive appearance as risk factors independently associated with
      development of DM. CONCLUSION: Patients with these risk factors should undergo
      total thyroidectomy and radioactive iodine ablation.

PMID- 28506523
TI  - Integration of population census and water point mapping data-A case study of
      Cambodia, Liberia and Tanzania.
AB  - Sustainable Development Goal (SDG) 6 has expanded the Millennium Development
      Goals' focus from improved drinking-water to safely managed water services. This
      expanded focus to include issues such as water quality requires richer monitoring
      data and potentially integration of datasets from different sources. Relevant
      data sets include water point mapping (WPM), the survey of boreholes, wells and
      other water points, census and household survey data. This study examined
      inconsistencies between population census and WPM datasets for Cambodia, Liberia
      and Tanzania, and identified potential barriers to integrating the two datasets
      to meet monitoring needs. Literatures on numbers of people served per water point
      were used to convert WPM data to population served by water source type per area
      and compared with census reports. For Cambodia and Tanzania, discrepancies with
      census data suggested incomplete WPM coverage. In Liberia, where the data sets
      were consistent, WPM-derived data on functionality, quantity and quality of
      drinking water were further combined with census area statistics to generate an
      enhanced drinking-water access measure for protected wells and springs. The
      process revealed barriers to integrating census and WPM data, including exclusion
      of water points not used for drinking by households, matching of census and WPM
      source types; temporal mismatches between data sources; data quality issues such
      as missing or implausible data values, and underlying assumptions about
      population served by different water point technologies. However, integration of
      these two data sets could be used to identify and rectify gaps in WPM coverage.
      If WPM databases become more complete and the above barriers are addressed, it
      could also be used to develop more realistic measures of household drinking-water
      access for monitoring.

PMID- 28506524
TI  - Contemporary Incidence and Cancer Control Outcomes of Primary Neuroendocrine
      Prostate Cancer: A SEER Database Analysis.
AB  - INTRODUCTION: Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity.
      We aimed at providing contemporary data on incidence and survival figures of de
      novo NEPC. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End
      Results (SEER) database, we identified 309 individuals with de-novo NEPC
      diagnosed between 2004 and 2013. We evaluated age-adjusted incidence rates over
      the study. Kaplan-Meier analyses assessed overall survival (OS) after
      stratification according to histologic subtype, metastatic status, and treatment.
      Cox regression analyses tested the predictors of overall mortality, after
      adjusting for confounders. RESULTS: A total of 309 cases of NEPC were identified
      from 510,913 cases of prostate cancer. Metastatic disease was identified in 198
      (64.1%) cases. The most common histologic subtype (n = 186; 60.2%) was small-cell
      carcinoma (SCC). The age-adjusted incidence of NEPC significantly increased over
      the study span. However, this increase only affected SCC (from 0.13/1,000,000
      person-years in 2004 to 0.30/1,000,000 person-years in 2013; P = .001). Median
      survival for NEPC was 10 months. After stratification by metastatic status, no
      difference was observed according to SCC versus non-SCC. Treatment with radical
      prostatectomy improved OS only among individuals with non-metastatic disease,
      whereas radiation therapy did not affect OS rates. In multivariable Cox
      regression analyses predicting overall mortality, metastatic stage (hazard ratio,
      1.52; 95% confidence interval, 1.12-2.06; P < .01) and radical prostatectomy
      (hazard ratio, 0.38; 95% confidence interval, 0.20-0.74; P < .01) achieved
      independent predictor status. CONCLUSION: De-novo NEPC is extremely rare and will
      be encountered in clinical practice by few urologists. Most cases are metastatic
      at diagnosis. Prognosis is poor regardless of histologic type, especially in
      metastatic stage.

PMID- 28506526
TI  - Molecular Simulation and Biochemical Studies Support an Elevator-type Transport
      Mechanism in EIIC.
AB  - Enzyme IIC (EIIC) is a membrane-embedded sugar transport protein that is part of
      the phosphoenolpyruvate-dependent phosphotransferases. Crystal structures of two
      members of the glucose EIIC superfamily, bcChbC in the inward-facing conformation
      and bcMalT in the outward-facing conformation, were previously solved. Comparing
      the two structures led us to the hypothesis that sugar translocation could be
      achieved by an elevator-type transport mechanism in which a transport domain
      binds to the substrate and, through rigid body motions, transports it across the
      membrane. To test this hypothesis and to obtain more accurate descriptions of
      alternate conformations of the two proteins, we first performed collective
      variable-based steered molecular dynamics (CVSMD) simulations starting with the
      two crystal structures embedded in model lipid bilayers, and steered their
      transport domain toward their own alternative conformation. Our simulations show
      that large rigid-body motions of the transport domain (55 degrees  in rotation
      and 8 A in translation) lead to access of the substrate binding site to the
      alternate side of the membrane. H-bonding interactions between the sugar and the
      protein are intact, although the side chains of the binding-site residues were
      not restrained in the simulation. Pairs of residues in bcMalT that are far apart
      in the crystal structure become close to each other in the simulated model. Some
      of these pairs can be cross-linked by a mercury ion when mutated to cysteines,
      providing further support for the CVSMD-generated model. In addition, bcMalT
      binds to maltose with similar affinities before and after the cross-linking,
      suggesting that the binding site is preserved after the conformational change. In
      combination, these results support an elevator-type transport mechanism in EIIC.

PMID- 28506525
TI  - How Does Mg2+ Modulate the RNA Folding Mechanism: A Case Study of the G:C W:W
      Trans Basepair.
AB  - Reverse Watson-Crick G:C basepairs (G:C W:W Trans) occur frequently in different
      functional RNAs. This is one of the few basepairs whose gas-phase-optimized
      isolated geometry is inconsistent with the corresponding experimental geometry.
      Several earlier studies indicate that through post-transcriptional modification,
      direct protonation, or coordination with Mg2+, accumulation of positive charge
      near N7 of guanine can stabilize the experimental geometry. Interestingly, recent
      studies reveal significant variation in the position of putatively bound Mg2+.
      This, in conjunction with recently raised doubts regarding some of the Mg2+
      assignments near the imino nitrogen of guanine, is suggestive of the existence of
      multiple Mg2+ binding modes for this basepair. Our detailed investigation of Mg2+
      bound G:C W:W Trans pairs occurring in high-resolution RNA crystal structures
      shows that they are found in 14 different contexts, eight of which display Mg2+
      binding at the Hoogsteen edge of guanine. Further examination of occurrences in
      these eight contexts led to the characterization of three different Mg2+ binding
      modes: 1) direct binding via N7 coordination, 2) direct binding via O6
      coordination, and 3) binding via hydrogen-bonding interaction with the first
      shell water molecules. In the crystal structures, the latter two modes are
      associated with a buckled and propeller-twisted geometry of the basepair.
      Interestingly, respective optimized geometries of these different Mg2+ binding
      modes (optimized using six different DFT functionals) are consistent with their
      corresponding experimental geometries. Subsequent interaction energy calculations
      at the MP2 level, and decomposition of its components, suggest that for G:C W:W
      Trans , Mg2+ binding can fine tune the basepair geometries without compromising
      with their stability. Our results, therefore, underline the importance of the
      mode of binding of Mg2+ ions in shaping RNA structure, folding and function.

PMID- 28506527
TI  - Ancestral Interactions of Ribosomal RNA and Ribosomal Proteins.
AB  - We have proposed that the ancient ribosome increased in size during early
      evolution by addition of small folding-competent RNAs. In this Accretion Model,
      small RNAs and peptides were subsumed onto subunit surfaces, gradually encasing
      and freezing previously acquired components. The model predicts that appropriate
      rRNA fragments have inherited local autonomy of folding and local autonomy of
      assembly with ribosomal proteins (rProteins), and that the rProtein and rRNA are
      co-chaperones. To test these predictions, we investigate the rRNA interactions of
      rProtein uL23 and its tail, uL23tail, which is a beta-hairpin that penetrates
      deep into the core of the large ribosomal subunit. In the assembled ribosome,
      uL23tail associates with Domain III of the rRNA and a subdomain called
      "DIIIcore". Here using band shift assays, fluorescence Job plots, and yeast three
      hybrid assays, we investigate the interactions of rProtein uL23 and its tail with
      Domain III and with DIIIcore rRNA. We observe rRNA1-uL23tail1 complexes in the
      absence of Mg2+ ions and rRNA1-uL23tailn (n > 1) complexes in the presence of
      Mg2+ ions. By contrast, the intact uL23 rProtein binds in slightly
      anticooperative complexes of various stoichiometries. The globular and tail
      regions of rProtein uL23 are distinctive in their folding behaviors and the ion
      dependences of their association with rRNA. For the globular region of the
      rProtein, folding is independent of rRNA, and rRNA association is predominantly
      by nonelectrostatic mechanisms. For the tail region of the protein, folding
      requires rRNA, and association is predominantly by electrostatic mechanisms. We
      believe these protein capabilities could have roots in ancient evolution and
      could be mechanistically important in co-chaperoning the assembly of the
      ribosome.

PMID- 28506528
TI  - Emerging roles of basophils in allergic inflammation.
AB  - Basophils have long been neglected in immunological studies because they were
      regarded as only minor relatives of mast cells. However, recent advances in
      analytical tools for basophils have clarified the non-redundant roles of
      basophils in allergic inflammation. Basophils play crucial roles in both IgE
      dependent and -independent allergic inflammation, through their migration to the
      site of inflammation and secretion of various mediators, including cytokines,
      chemokines, and proteases. Basophils are known to produce large amounts of IL-4
      in response to various stimuli. Basophil-derived IL-4 has recently been shown to
      play versatile roles in allergic inflammation by acting on various cell types,
      including macrophages, innate lymphoid cells, fibroblasts, and endothelial cells.
      Basophil-derived serine proteases are also crucial for the aggravation of
      allergic inflammation. Moreover, recent reports suggest the roles of basophils in
      modulating adaptive immune responses, particularly in the induction of Th2
      differentiation and enhancement of humoral memory responses. In this review, we
      will discuss recent advances in understanding the roles of basophils in allergic
      inflammation.

PMID- 28506529
TI  - Guillain-Barre syndrome in a patient with renal cell carcinoma following the
      first course of pazopanib therapy.
AB  - Pazopanib, one of the antiangiogenic drugs, has recently become a first-line
      treatment for metastatic renal cell carcinoma. The most common adverse effects of
      pazopanib include diarrhea, fatigue, and nausea, but neuropathic complication has
      not been documented. Here, we report the first case of a patient with metastatic
      renal cell carcinoma who developed acute neuropathy mimicking Guillain-Barre
      syndrome following the first course of pazopanib therapy. A 75-year-old man with
      a metastatic renal cell carcinoma was admitted for rapidly progressive weakness
      and numbness in the extremities after the first course of pazopanib therapy.
      Neurological examination revealed symmetrical distal limb weakness, sensory
      disturbance, and areflexia. Based on the clinical pictures, conduction slowing on
      the nerve conduction studies of the extremities and albuminocytologic
      dissociation on the cerebrospinal fluid examination, a diagnosis of Guillain
      Barre syndrome was made. After discontinuation of pazopanib and a subsequent high
      dose intravenous immunoglobulin therapy, symptoms rapidly resolved and the
      patient became ambulatory with a cane. Serological and neuroradiological
      examinations failed to reveal any possible causes for the neuropathy other than
      pazopanib. While the benefits of pazopanib for metastatic renal cell carcinoma
      far outweigh this neurotoxic effect, physicians prescribing this drug should be
      aware of this rare complication of neuropathy.

PMID- 28506530
TI  - Ipsilateral proximal and shaft femoral fractures.
AB  - PURPOSE: To study the management and evaluate anatomical and functional outcomes
      of patients with ipsilateral proximal and shaft femoral fractures. METHODS: A
      retrospective, descriptive and analytic study lasted for ten years and a half
      ranging from January 1, 2005 to June 30, 2015. The following parameters were
      studied: epidemiology, fracture characteristics, therapeutic, anatomical and
      functional outcomes. The correlation between different parameters was analyzed
      with Fischer test. The significant threshold was defined for p value <0.05.
      RESULTS: Ten medical files were registered. There were 7 men and 3 women, with a
      sex ratio of 2.33. The average age was 46 years (range: 29-62 years). It was
      about traffic road accidents in all cases. Motorcycle-motorcycle and motorcycle
      car collision were most frequent. Average admission delay was 7 h (range: 1.5-24
      h). Left side was most reached in 8 cases. According to Garden classification,
      there was type III cervical fracture in 2 cases, type II in 1 case and type IV in
      1 case. According to Ender classification, there was type I trochanteric fracture
      in 3 cases, type VI in 2 cases and type VII in 1 case. According to AO
      classification, there was type A shaft fracture in 6 cases (A2 in 4 cases and A3
      in 2 cases), type B in 2 cases (B1 in 1 case and B2 in 1 case) and type C in 2
      cases (C1 in 1 case and C2 in 1 case). Average surgical delay was 28.7 days
      (range: 11-61 days). For proximal femoral fracture, Moore prosthesis was used in
      1 case, blade plate 130 degrees  in 2 cases, long Gamma nail in 4 cases, double
      screwing in 2 cases and dynamic hip screw in 1 case. For shaft femoral fracture,
      blade plate 95 degrees  was used in 3 cases, low compressive plate in 2 cases.
      Osseous contention was achieved in 4 cases with long Gamma nail and in 1 case
      with long blade plate 130 degrees . Nonunion of cervical fracture was achieved in
      2 cases. The average osseous healing delay was 5.14 months (range: 3-12 months)
      for proximal femoral fracture and 5 months (range: 3-8 months) for shaft femoral
      fractures. According to Friedman and Wyman criteria, functional results were good
      in 4 cases, average in 4 cases and bad in 2 cases. Regarding implants, healing
      delay showed no statistic difference between one-implant group and two-implant
      group (p = 0.52), and among the patients with different functional outcomes (p =
      0.52). Functional outcomes showed no statistic difference between one-implant
      group and two-implant group (p = 0.46). CONCLUSION: Ipsilateral proximal and
      shaft femoral fractures are relatively uncommon in our daily activities. It is
      difficult to recognize proximal femoral fractures which are unnoticed. Results
      are generally good if the doctors take the two fractures into account in the
      management.

PMID- 28506531
TI  - Parkinson's disease and pregnancy: An updated review.
AB  - Pregnancy does not often occur in the setting of Parkinson's disease (PD) as the
      most common age of onset is beyond the childbearing years, yet management of
      these two conditions is crucial for the health of both mother and child. Here we
      review treatment data of PD during pregnancy, primarily from case reports and
      drug registries, and focus on available evidence regarding the pregnancy risks
      for patient and fetus. Historically, it was reported that many women had
      worsening of symptoms during pregnancy but this may be because anti-parkinsonian
      medications were not recommended or were under dosed. Levodopa has the best
      safety data for use in pregnancy and amantadine should be avoided in women who
      are pregnant or trying to become pregnant. The data for other pharmacological and
      surgical treatments is less clear. There is no evidence that women with PD have
      higher rates of birth or fetal complications.

PMID- 28506532
TI  - Accreditation of Biosafe Clinical-Grade Human Embryonic Stem Cells According to
      Chinese Regulations.
AB  - Human embryonic stem cells (hESCs) are promising in regenerative medicine.
      Although several hESC-based clinical trials are under way, a widely accepted
      standard of clinical-grade cells remains obscure. To attain a completely xeno
      free clinical-grade cell line, the system must be free of xenogenic components,
      the cells must have a comprehensive set of functions, and good manufacturing
      practice conditions must be used. In this study, following these criteria, we
      successfully derived two hESC lines, which were thereby considered "clinical
      grade embryonic stem cells". In addition to the primary capacity for
      pluripotency, these two cell lines were efficiently differentiated into various
      types of clinical-grade progeny. Importantly, the cells were recognized by the
      National Institutes for Food and Drug Control of China for further eligible
      accreditation. These data indicate that we have established completely xeno-free
      clinical-grade hESC lines and their derivatives, which will be valuable for the
      foundation of an international standard for clinical-grade cells for therapy.

PMID- 28506534
TI  - NEUROD1 Instructs Neuronal Conversion in Non-Reactive Astrocytes.
AB  - Currently, all methods for converting non-neuronal cells into neurons involve
      injury to the brain; however, whether neuronal transdifferentiation can occur
      long after the period of insult remains largely unknown. Here, we use the
      transcription factor NEUROD1, previously shown to convert reactive glial cells to
      neurons in the cortex, to determine whether astrocyte-to-neuron
      transdifferentiation can occur under physiological conditions. We utilized adeno
      associated virus 9 (AAV9), which crosses the blood-brain barrier without injury,
      to deliver NEUROD1 to astrocytes through an intravascular route. Interestingly,
      we found that a small, but significant number of non-reactive astrocytes
      converted to neurons in the striatum, but not the cortex. Moreover, astrocytes
      cultured to minimize their proliferative potential also exhibited limited
      neuronal transdifferentiation with NEUROD1 expression. Our results show that a
      single transcription factor can induce astrocyte-to-neuron conversion under
      physiological conditions, potentially facilitating future clinical approaches
      long after the acute injury phase.

PMID- 28506533
TI  - Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential
      Therapeutic Target for Myelin Repair.
AB  - Schwann cells play a crucial role in successful nerve repair and regeneration by
      supporting both axonal growth and myelination. However, the sources of human
      Schwann cells are limited both for studies of Schwann cell development and
      biology and for the development of treatments for Schwann cell-associated
      diseases. Here, we provide a rapid and scalable method to produce self-renewing
      Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using
      combined sequential treatment with inhibitors of the TGF-beta and GSK-3 signaling
      pathways, and with neuregulin-1 for 18 days under chemically defined conditions.
      Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann
      cells that were functionally confirmed by their secretion of neurotrophic factors
      and their myelination capacity in vitro and in vivo. We propose that hPSC-derived
      SCPs are a promising, unlimited source of functional Schwann cells for treating
      demyelination disorders and injuries to the peripheral nervous system.

PMID- 28506536
TI  - Checkpoint inhibition and melanoma: Considerations in treating the older adult.
AB  - The incidence of melanoma and associated mortality rate from advanced disease in
      older adults is increasing over time. Checkpoint inhibitors have demonstrated a
      survival benefit for the treatment of stage IV or unresectable stage III disease
      and have become one of the standards of care. Data suggests that adults aged 65
      and older benefit from treatment with checkpoint inhibitors without an increased
      incidence in adverse events. However, clinicians should be aware of the potential
      side effects of this class of medications and how to manage them in older adults.

PMID- 28506537
TI  - Epitope-specific immunotherapy: a vaccine for coeliac disease?

PMID- 28506535
TI  - SCA-1 Expression Level Identifies Quiescent Hematopoietic Stem and Progenitor
      Cells.
AB  - Blood cell generation depends on continuous cellular output by the sequential
      hierarchy of hematopoietic stem cell (HSC) and progenitor populations that all
      contain quiescent and actively cycling cells. Hematopoietic stem and progenitor
      cells (HSPCs) express the surface molecule Stem cell antigen 1 (SCA-1/LY6A).
      Using histone 2B-red fluorescent fusion protein label retention and cell-cycle
      reporter mice, we demonstrate that high SCA-1 expression (SCA-1hi) identifies not
      only quiescent HSCs but quiescent cells on all hierarchical levels within the
      lineage-SCA-1+KIT+ (LSK) population. Each transplanted SCA-1hi HSPC population
      also displayed self-renewal potential superior to that of the respective SCA-1lo
      population. SCA-1 expression is inducible by type I interferon (IFN). We show,
      however, that quiescence and high self-renewal capacity of cells with brighter
      SCA-1 expression at steady state were independent of type I IFN signaling. We
      conclude that SCA-1 expression levels can be used to prospectively isolate
      functionally heterogeneous HSPC subpopulations.

PMID- 28506539
TI  - Description of a new soft tick species (Acari: Argasidae: Ornithodoros)
      associated with stream-breeding frogs (Anura: Cycloramphidae: Cycloramphus) in
      Brazil.
AB  - In this study, we present a morphological description of immature and adult
      specimens of Ornithodoros saraivai n. sp., a tick associated with the frog
      Cycloramphus boraceiensis (Cycloramphidae) at Sao Sebastiao island, located in
      the Sao Paulo state seaboard, Brazil. While larvae of O. saraivai are
      ecologically related to Ornithodoros faccinii, another soft tick associated with
      cycloramphids, the combination of 7 sternal pairs, 16 dorsal pairs, a pyriform
      dorsal plate and a partially toothed hypostome constitute unique characters of
      the O. saraivai larvae. One undetermined nymphal instar and adults of O. saraivai
      are similar to mature specimens of the Ornithodoros talaje species group;
      however, the O. saraivai specimens can be recognized by the presence of a robust
      bean-shaped spiracle with a large spiracular plate and more than two long seta in
      palpal article I. Identical partial sequences of the mitochondrial 16S rDNA gene
      confirmed the identity for all collected stages and for two cohorts of laboratory
      reared larvae of O. saraivai. A Bayesian and Maximum Parsimony inferred
      phylogenetic trees support the position of O. saraivai in a clade with O.
      faccinii, suggesting the existence of an Ornithodoros lineage that evolved in
      association with amphibians.

PMID- 28506540
TI  - A randomized controlled trial of an intervention program to Brazilian mothers who
      use corporal punishment.
AB  - This study evaluated a positive parenting program to Brazilian mothers who used
      corporal punishment with their children. The intervention was conducted in four
      agencies serving vulnerable children, and at a home replica laboratory at the
      University. Mothers who admitted using corporal punishment were randomly assigned
      between experimental (n=20) and control group (n=20). The program consisted of 12
      individual sessions using one unit from Projeto Parceria (Partnership Project),
      with specific guidelines and materials on positive parenting, followed by
      observational sessions of mother-child interaction with live coaching and a video
      feedback session in the lab. The study used an equivalent group experimental
      design with pre/post-test and follow-up, in randomized controlled trials.
      Measures involved: Initial Interview; Strengths and Difficulties Questionnaire
      (SDQ) - parent and child versions; Beck Depression Inventory (BDI); observational
      sessions with a protocol; and a Program Evaluation by participants. Analysis of
      mixed models for repeated measures revealed significant positive effects on the
      BDI and SDQ total scores, as well as less Conduct problems and Hyperactivity in
      SDQ measures from the experimental group mothers, comparing pre with post-test.
      Observational data also indicated significant improvement in positive interaction
      from the experimental group mothers at post-test, in comparison with controls. No
      significant results were found, however, in children's observational measures.
      Limitations of the study involved using a restricted sample, among others.
      Implications for future research are suggested.

PMID- 28506538
TI  - Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease:
      two randomised, double-blind, placebo-controlled phase 1 studies.
AB  - BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a
      permanent immune intolerance to gluten. We developed a therapeutic vaccine,
      Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of
      three peptides that include immunodominant epitopes for gluten-specific CD4
      positive T cells. The vaccine is intended to engage and render gluten-specific
      CD4-positive T cells unresponsive to further antigenic stimulation. We assessed
      the safety and pharmacodynamics of the vaccine in patients with coeliac disease
      on a gluten-free diet. METHODS: We did two randomised, double-blind, placebo
      controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and
      the USA, in HLA-DQ2.5-positive patients aged 18-70 years who had coeliac disease
      and were on a gluten-free diet. In the screening period for ascending dose
      cohorts, participants were randomly assigned (1:1) by central randomisation with
      a simple block method to a double-blind crossover, placebo-controlled oral gluten
      challenge. Participants with a negative interferon gamma release assay to Nexvax2
      peptides after the screening oral gluten challenge were discontinued before
      dosing. For the biopsy cohorts, the screening period included an endoscopy, and
      participants with duodenal histology who had a Marsh score of greater than 1 were
      discontinued before dosing. Participants were subsequently randomly assigned to
      either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts
      (1:1) by central randomisation with a simple block method. In the three-dose
      study, participants received either Nexvax2 60 MUg, 90 MUg, or 150 MUg weekly, or
      placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2
      at the maximum tolerated dose (MTD) or placebo. In the 16-dose study,
      participants received Nexvax2 150 MUg or 300 MUg or placebo twice weekly over 53
      days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD
      or placebo. In the 4-week post-treatment period, ascending dose cohorts underwent
      a further double-blind crossover, placebo-controlled oral gluten challenge, which
      had a fixed sequence, and biopsy cohorts had a gastroscopy with duodenal biopsies
      and quantitative histology within 2 weeks without oral gluten challenge.
      Participants, investigators, and study staff were masked to the treatment
      assignment, except for the study pharmacist. The primary endpoint was the number
      and percentage of adverse events in the treatment period in an intention-to-treat
      analysis. Both trials were completed and closed before data analysis. Trials were
      registered with the Australian New Zealand Clinical Trials Registry, numbers
      ACTRN12612000355875 and ACTRN12613001331729. FINDINGS: Participants were enrolled
      from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3,
      2012, to Sept 10, 2013, in the 16-dose study. Overall, 62 (57%) of 108
      participants were randomly assigned after oral gluten challenge and 20 (71%) of
      28 participants were randomly assigned after endoscopy. In the three-dose study,
      nine participants were randomly allocated to Nexvax2 60 MUg and three to placebo
      (first cohort), nine were allocated to Nexvax2 90 MUg and four to placebo (second
      cohort), eight were allocated to Nexvax2 150 MUg and four to placebo (third
      cohort), and three were allocated to Nexvax2 150 MUg and three to placebo (biopsy
      cohort). In the 16-dose study, eight participants were randomly allocated to
      Nexvax2 150 MUg and four to placebo (first cohort), ten were allocated to Nexvax2
      300 MUg and three to placebo (second cohort), and seven were allocated to Nexvax2
      150 MUg and seven to placebo (biopsy cohort). The MTD for Nexvax2 was 150 MUg
      because of transient, acute gastrointestinal adverse events with onset 2-5 h
      after initial doses of the vaccine, similar to those caused by gluten ingestion.
      In the ascending dose cohorts in the three-dose study, six (55%) of 11 placebo
      recipients, five (56%) of nine who received Nexvax2 60 MUg, seven (78%) of nine
      who received Nexvax2 90 MUg, and five (63%) of eight who received Nexvax2 150 MUg
      had at least one treatment-emergent adverse event, as did all three (100%)
      placebo recipients and one (33%) of three Nexvax2 150 MUg recipients in the
      biopsy cohort. In the ascending dose cohorts of the 16-dose study, five (71%) of
      seven placebo-treated participants, six (75%) of eight who received Nexvax2 150
      MUg, and all ten (100%) who received Nexvax2 300 MUg had at least one treatment
      emergent adverse event, as did six (86%) of seven placebo recipients and five
      (71%) of seven Nexvax2 150 MUg recipients in the biopsy cohort. Vomiting, nausea,
      and headache were the only treatment-emergent adverse events that occurred in at
      least 5% of participants in either study. Among participants given the MTD, eight
      gastrointestinal treatment-emergent adverse events occurred in four (50%) of
      eight participants in the third cohort and none (0%) of three participants in the
      biopsy cohort in the three-dose study, and five events occurred in five (63%) of
      eight participants in the first cohort and three events in two (29%) of seven
      participants in the biopsy cohort of the 16-dose study. Median villous height to
      crypt depth ratio in distal duodenal biopsies was not significantly different
      between those who received the vaccine at the MTD on either schedule and those
      who received placebo. Of the participants who completed the post-treatment oral
      gluten challenge per protocol, interferon gamma release assay to Nexvax2 peptides
      was negative (responders to treatment) in two (22%) of nine placebo-treated
      participants in the three-dose study versus two (33%) of six who received Nexvax2
      60 MUg, five (63%) of eight who received Nexvax2 90 MUg, and six (100%) of six
      who received Nexvax2 150 MUg (p=0.007); in the 16-dose study, none (0%) of five
      placebo-treated participants had a negative assay versus six (75%) of eight who
      received Nexvax2 150 MUg (p=0.021). INTERPRETATION: The MTD of Nexvax2 was 150
      MUg for twice weekly intradermal administration over 8 weeks, which modified
      immune responsiveness to Nexvax2 peptides without deterioration in duodenal
      histology. The gastrointestinal symptoms that followed the first intradermal
      administration of the vaccine resembled those associated with oral gluten
      challenge. These findings support continued clinical development of this
      potential therapeutic vaccine for coeliac disease. FUNDING: ImmusanT.

PMID- 28506541
TI  - Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta
      analysis Comparing Preoperative and Intraoperative Assessments During Cardiac
      Surgery.
AB  - OBJECTIVE: To assess differences in mitral regurgitation (MR) grade between the
      preoperative and the intraoperative evaluations. DESIGN: Systematic review and
      meta-analysis of 6 observational studies found from MEDLINE and EMBASE. SETTING:
      Cardiac surgery. PARTICIPANTS: One hundred thirty-seven patients. INTERVENTION:
      Comparison between the preoperative MR assessment and the intraoperative
      evaluation conducted under general anesthesia (GA), with or without "hemodynamic
      matching" (HM) (artificial increase of afterload). MEASUREMENTS AND MAIN RESULTS:
      The primary outcome was the difference between the preoperative and
      intraoperative MR grade under "GA-only" or "after-HM." Secondary analyses
      addressed differences according to effective regurgitant orifice area (EROA),
      regurgitant volume (RVol), color-jet area, and vena contracta width. Risk of MR
      underestimation was found under "GA-only" (SMD: 0.55; 95% confidence interval
      [CI], 0.31-0.79, p < 0.00001), but not "after-HM" (SMD: -0.16; 95% CI, -0.46 to
      0.13, p = 0.27). Under "GA-only", EROA had a trend toward underestimation (p =
      0.07), RVol was reliable (p = 0.17), while reliance on color-jet area and vena
      contracta width incur risk of underestimation (both p = 0.003). After HM, EROA
      accurately reflected preoperative MR (p = 0.68) while RVol had a trend toward
      overestimation (p = 0.05). The overall reported incidence of misdiagnoses was
      slightly more common under "GA-only" (mean 48%, 39% underestimation, 9%
      overestimation; range: 32%-57%) than "after-HM" (mean 41%, 12% underestimation,
      29% overestimation; range: 33%-50%). Only the minority of misdiagnoses were
      clinically relevant: underestimation was around 10% (both approaches), but 18%
      had clinically significant overestimation "after-HM" as compared with 3% under GA
      only. CONCLUSIONS: Intraoperative assessment under "GA-only" significantly
      underestimated MR. A more accurate intraoperative evaluation can be obtained with
      afterload manipulation, although HM strategy carries high risk of clinically
      significant overestimation.

PMID- 28506542
TI  - Coronary Sinus Isoflurane Concentration in Cardiac Surgery.
AB  - OBJECTIVE: Volatile anesthetic agents such as isoflurane may be associated with
      fewer adverse myocardial events compared with total intravenous anesthesia in
      cardiac surgery. The authors aimed to determine whether reasonable isoflurane
      concentrations at tissue level were being achieved to protect the myocardium
      using this agent. The isoflurane concentration in myocardium has never been
      measured. The primary aim was to sample coronary sinus (CS) blood and measure its
      isoflurane concentration. Secondary aims were to determine whether the CS blood
      concentration would equilibrate with the arterial blood concentration and the
      relationship of CS blood concentration with oxygenator exhaust isoflurane
      concentrations during cardiopulmonary bypass (CPB). DESIGN: Prospective,
      observational study. SETTING: Single-center university hospital. PARTICIPANTS:
      The study comprised 23 patients undergoing cardiac surgery using CPB and
      isoflurane. MEASUREMENTS AND MAIN RESULTS: Shortly after initiation of CPB and
      insertion of a CS retrograde cardioplegia catheter but before aortic cross
      clamping, CS blood was aspirated, followed by radial artery blood, which then
      were analyzed for isoflurane with gas chromatography and mass spectrometry. The
      oxygenator exhaust isoflurane level was measured with an anesthetic gas analyzer.
      The mean arterial and CS isoflurane concentrations were 87.7 +/- 50.1 and 73.0 +/
      42.9 MUg/mL, respectively. There was a significant mean difference of 14.7
      MUg/mL (95% confidence interval 6.7-22.8) between CS and arterial isoflurane
      concentrations. Oxygenator exhaust isoflurane levels were correlated positively
      with those in the CS blood (r = 0.68, p < 0.001) and arterial blood (r = 0.72, p
      < 0.001). CONCLUSIONS: This was the first study in which CS blood was sampled and
      measured for isoflurane concentration. The CS isoflurane concentration could be
      estimated from the isoflurane concentration in the oxygenator exhaust gas.
      However, the value of this relationship is limited because the CS isoflurane
      concentration does not accurately represent its myocardial levels during CPB.

PMID- 28506543
TI  - Implementing a pharmacist-led, individualized medication assessment and planning
      (iMAP) intervention to reduce medication related problems among older adults with
      cancer.
AB  - OBJECTIVES: Medication-related problems (MRP) affecting older adults are a
      significant healthcare concern and account for billions in medication-related
      morbidity. Cancer therapies can increase the prevalence of MRP. The objective of
      this study was to test the feasibility and effectiveness of implementing a
      pharmacist-led individualized medication assessment and planning (iMAP)
      intervention on the number and prevalence of MRP. MATERIALS AND METHODS: This
      prospective pilot study enrolled oncology outpatients aged >=65years.
      Intervention feasibility encompassed recommendation acceptance rate and
      intervention delivery time. The intervention was facilitated by pharmacists where
      patients received comprehensive medication management at baseline and at the 30-
      and 60-day follow-up. RESULTS: Forty-eight eligible patients enrolled and 41
      patients (85.4%) were included in the analysis. Mean age was 79.1years [range 65
      101]; 66% women, 83% Caucasian, mean comorbidity count was 7.76. Forty-six
      percent of the pharmacist recommendations were accepted and the prevalence of MRP
      at baseline versus 60-day follow-up decreased by 20.5%. The average time to
      conduct the initial session was 22min versus 15min for the follow-up sessions.
      Resources needed included a tracking system for scheduling follow-up calls and a
      database for tracking acceptance of recommendations. A total of 123 MRP were
      identified in 95% of patients (N=39) with a mean of 3 MRP per patient. The mean
      reduction in number of MRP (3 at baseline versus 1.6 at 60-day follow-up) was
      45.5%. CONCLUSIONS: The pharmacist-led iMAP intervention was feasible and
      effective at reducing MRP. Additional inter-professional medication safety based
      interventions measuring patient-reported outcomes are still needed.

PMID- 28506545
TI  - Travel for Abortion Services in Alabama and Delays Obtaining Care.
AB  - BACKGROUND: In 2013, Alabama required women seeking abortion to have a
      consultation visit followed by a 24-hour waiting period. These requirements may
      adversely affect return for timely care among those traveling long distances for
      services. METHODS: Using de-identified billing data from two Alabama clinics for
      all abortion encounters in 2013, we calculated the distance traveled from women's
      residential zip code and the number of days between their in-person consultation
      and procedure visits. To assess the associations between distance traveled and
      return for an abortion visit and length of interval between visits, we used
      logistic and ordinal logistic regression, respectively. RESULTS: Of the 2,730
      women attending a consultation visit, 58% traveled less than 25 miles one way to
      the clinic, 13% traveled 25 to 49 miles, 21% traveled 50 to 100 miles, and 8%
      traveled more than 100 miles. Overall, 19% of women did not return to either
      clinic for an abortion procedure after their consultation. Distance traveled was
      not associated with return for an abortion visit (odds ratio, 1.04; 95%
      confidence interval, 0.76-1.42). Among women who returned, 59% had less than 7
      days, 29% had 7 to 13 days, and 12% had 14 or more days between their
      consultation and procedure visits. Compared with women traveling less than 25
      miles, those traveling 50 to 100 miles had significantly longer intervals between
      visits (odds ratio, 1.25; 95% confidence interval, 1.01-1.56). CONCLUSIONS:
      Although most women returned for their abortion procedure, many traveling long
      distances had a week or more between visits. Because delays may limit women's
      options for affordable abortion care, evidence-based policies should be adopted
      to facilitate women's timely receipt of services.

PMID- 28506544
TI  - Development of the Vanderbilt Assessment for Delirium in Infants and Children to
      Standardize Pediatric Delirium Assessment By Psychiatrists.
AB  - BACKGROUND: Pediatric delirium assessment is complicated by variations in
      baseline language and cognitive skills, impairment during illness, and absence of
      pediatric-specific modifiers within the Diagnostic and Statistical Manual of
      Mental Disorders delirium criterion. OBJECTIVE: To develop a standardized
      approach to pediatric delirium assessment by psychiatrists. METHODS: A
      multidisciplinary group of clinicians used Diagnostic and Statistical Manual
      criterion as the foundation for the Vanderbilt Assessment for Delirium in Infants
      and Children (VADIC). Pediatric-specific modifiers were integrated into the
      delirium criterion, including key developmental and assessment variations for
      children. The VADIC was used in clinical practice to prospectively assess
      critically ill infants and children. The VADIC was assessed for content validity
      by the American Academy of Child and Adolescent Psychiatry Delirium Special
      Interest Group. RESULTS: The American Academy of Child and Adolescent Psychiatry
      Delirium Special Interest Group determined that the VADIC demonstrated high
      content validity. The VADIC (1) preserved the core Diagnostic and Statistical
      Manual delirium criterion, (2) appropriately paired interactive assessments with
      key criterion based on development, and (3) addressed confounders for delirium. A
      cohort of 300 patients with a median age of 20 months was assessed for delirium
      using the VADIC. Delirium prevalence was 47%. CONCLUSION: The VADIC provides a
      comprehensive framework to standardize pediatric delirium assessment by
      psychiatrists. The need for consistency in both delirium education and diagnosis
      is highlighted given the high prevalence of pediatric delirium.

PMID- 28506546
TI  - A Model for Electronic Handoff Between the Emergency Department and Inpatient
      Units.
AB  - BACKGROUND: Patient handoffs between units can introduce risk and time delays.
      Verbal communication is the most common mode of handoff, but requires
      coordination between different parties. OBJECTIVE: We present an asynchronous
      patient handoff process supported by a structured electronic signout for
      admissions from the emergency department (ED) to the inpatient medicine service.
      METHODS: A retrospective review of patients admitted to the medical service from
      July 1, 2011 to June 30, 2015 at a tertiary referral center with 520 inpatient
      beds and 57,000 ED visits annually. We developed a model for structured
      electronic, asynchronous signout that includes an option to request verbal
      communication after review of the electronic handoff information. RESULTS: During
      the 2010 academic year (AY) all admissions used verbal communication for signout.
      The following academic year, electronic signout was implemented and 77.5% of
      admissions were accepted with electronic signout. The rate increased to 87.3% by
      AY 2014. The rate of transfer from floor to an intensive care unit within 24 h
      for the year before and 4 years after implementation of the electronic signout
      system was collected and calculated with 95% confidence interval. There was no
      statistically significant difference between the year prior and the years after
      the implementation. CONCLUSIONS: Our handoff model sought to maximize the
      opportunity for asynchronous signout while still providing the opportunity for
      verbal signout when deemed necessary. The process was rapidly adopted with the
      majority of patients being accepted electronically.

PMID- 28506547
TI  - Transcatheter mitral valve interventions for mitral regurgitation, with special
      focus on MitraClip: The position of Spanish, Portuguese and Italian
      interventional societies.
AB  - Mitral regurgitation is a common valvular heart disease and its prevalence is
      expected to increase with population ageing. In the recent years we have
      witnessed the evolution of several transcatheter devices to correct mitral
      regurgitation in patients at high-risk for surgery. Most of the evidence of the
      safety and efficacy of this new therapy comes from MitraClip studies. However,
      new alternatives have emerged with promising results. The aim of this position
      paper is to review the current evidence regarding patient selection, expected
      results and timing for transcatheter mitral valve interventions from the
      perspective of three European interventional societies.

PMID- 28506549
TI  - Impact of chronic obstructive pulmonary disease on in-hospital morbidity and
      mortality in patients with ST-segment elevation myocardial infarction treated by
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) presenting
      with ST-segment elevation myocardial infarction (STEMI) are less likely to
      beneficiate of primary percutaneous coronary intervention (pPCI), and have poorer
      prognosis. We aimed to evaluate the impact of COPD on the in-hospital outcomes of
      pPCI-treated STEMI patients. METHODS: Data were collected from 418 STEMI patients
      treated by pPCI. Inotropics and diuretics usage, cardiogenic shock, asystole,
      kidney dysfunction, and left ventricular ejection fraction were used as markers
      of hemodynamic complications. Atrial and ventricular fibrillation, conduction
      disorders, and antiarrhythmics usage were used as markers of arrhythmic
      complications. In-hospital mortality was evaluated. The associations between
      these parameters and COPD were assessed. RESULTS: COPD was present in 7.42% of
      STEMI patients. COPD patients were older (p=0.02) and less likely to receive beta
      blockers (OR 0.29; 95%CI 0.13-0.64; p<0.01). They had higher Killip class on
      admission (p<0.001), received more often inotropics (p<0.001) and diuretics
      (p<0.01), and presented more often atrial (p=0.01) and ventricular fibrillation
      (p=0.02). Unadjusted in-hospital mortality was higher in COPD patients (OR 4.18,
      95%CI 1.55-11.30, p<0.01). After adjustment for potentially confounding factors
      except beta-blockers, COPD remained an independent predictor of in-hospital
      mortality (p=0.02). After further adjustment with beta-blocker therapy, no excess
      mortality was noted in COPD patients. CONCLUSIONS: Despite being treated by pPCI,
      COPD patients with STEMI are more likely to develop hemodynamic and arrhythmic
      complications, and have higher in-hospital mortality. This appears to be due to
      lower beta-blockers usage in COPD patients. Increasing beta-blockers usage in
      COPD patients with STEMI may improve survival.

PMID- 28506548
TI  - Antiarrhythmic medication is superior to catheter ablation in suppressing
      supraventricular ectopic complexes in patients with atrial fibrillation.
AB  - BACKGROUND: Supraventricular ectopic complexes (SVEC) originating in the
      pulmonary veins are known triggers of atrial fibrillation (AF) which led to the
      development of pulmonary vein isolation for AF. However, the long-term prevalence
      of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication
      (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and
      CA and to estimate the association between baseline SVEC burden and AF burden
      during 24months of follow-up. METHODS: Patients with paroxysmal AF (N=260)
      enrolled in the MANTRA PAF trial were treated with AAD (N=132) or CA (N=128). At
      baseline and 3, 6, 12, 18 and 24months follow-up patients underwent 7-day Holter
      monitoring to assess SVEC and AF burden. We compared SVEC burden between
      treatments with Wilcoxon sum rank test. RESULTS: Patients treated with AAD had
      significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19
      [6-58] versus CA: 39 [14-125], p=0.003). SVEC burden increased post-procedurally
      followed by a decrease after CA whereas after AAD SVEC burden decreased and
      stabilized after 3months of follow-up. Patients with low SVEC burden had low AF
      burden after both treatments albeit this was more pronounced after CA at 24months
      of follow-up. CONCLUSION: AAD was superior to CA in suppressing SVEC burden after
      treatment of paroxysmal AF. After CA SVEC burden increased immediately post
      procedural followed by a decrease whereas after AAD an early decrease was
      observed. Lower SVEC burden was highly associated with lower AF burden during
      follow-up especially after CA.

PMID- 28506551
TI  - Early in-hospital variation of red blood cell distribution width predicts
      mortality in patients with acute heart failure.
AB  - BACKGROUND: Some studies showed that the value of red blood cell distribution
      width (RDW) at admission may predict clinical outcomes in patients with acutely
      decompensated heart failure (ADHF). Therefore, this study was planned to
      investigate whether in-hospital variations of RDW may also predict mortality in
      this condition. METHODS: The final study population consisted of 588 patients
      admitted to the local Emergency Department (ED), who were hospitalized for ADHF.
      The RDW was measured at ED admission and after 48h and 96h of hospital stay. In
      hospital variations from admission value, expressed as absolute variation
      (DeltaRDW) or percent variation (Delta%RDW), were then correlated with 30- and 60
      day mortality. RESULTS: Overall, 87 (14.8%) and 118 (20.1%) patients with ADHF
      died at 30 or 60days of follow-up. Delta%RDW after 96h of hospital stay
      independently predicted 30-day mortality (odds ratio, 1.12; 95% CI, 1.07-1.18).
      An increase >1% of Delta%RDW after 96h of hospital stay independently predicted
      both 30-day (odds ratio, 2.86; 95% CI, 1.67-4.97) and 60-day (odds ratio, 3.06;
      95% CI, 1.89-4.96) mortality. A similar trend was observed for DeltaRDW, since an
      increase after 96h of hospital stay was associated with a nearly 4-fold higher 30
      day mortality (odds ratio, 3.65; 95% CI, 2.02-6.15). CONCLUSION: Despite it
      remains unclear whether RDW is a real risk factor or an epiphenomenon in ADHF,
      these results suggest that more aggressive management may be advisable in ADHF
      patients with increasing anisocytosis during the first days of hospitalization.

PMID- 28506550
TI  - Cardioprotective efficacy of sevoflurane vs. propofol during induction and/or
      maintenance in patients undergoing coronary artery revascularization surgery
      without pump: A randomized trial.
AB  - PURPOSE: Pre and post-operative administration of sevoflurane in myocardial
      revascularization surgery provides enhanced cardioprotective effects exerted by
      pharmacologic pre- and post-conditioning, as compared to propofol. The
      identification of the enzymes involved in conditioning mechanisms is crucial to
      the understanding of the effects of sevoflurane in cardiac surgery patients. The
      impact of sevoflurane on another crucial target organ-the kidney-was also
      assessed. METHODS: Ninety patients undergoing off-pump myocardial
      revascularization surgery were allocated to receive either intra- and
      postoperative sevoflurane (SS), intraoperative sevoflurane and postoperative
      propofol (SP), or intra- and postoperative propofol (PP)). Troponin I and
      hemodynamic parameters were monitored during the first 48 postoperative hours;
      blood and urine samples were collected at baseline and at 24h to determine Akt,
      ERK1/2, PKG, iNO, bradykinin receptor, caspase 3, NT proBNP and urinary NGAL.
      RESULTS: The enzymes were overexpressed in the SS group, remained unchanged in
      the SP group, and decreased in the PP group. Renal function was best preserved in
      the SS group. CONCLUSIONS: The overexpression of enzymes induced by
      intraoperative anesthesia and postoperative sedation with sevoflurane reduces
      myocardial damage and improves renal function in patients undergoing off-pump
      myocardial revascularization surgery.

PMID- 28506552
TI  - The natural terthiophene alpha-terthienylmethanol induces S phase cell cycle
      arrest of human ovarian cancer cells via the generation of ROS stress.
AB  - Ovarian cancer is the most lethal gynecological malignancy worldwide. Thiophenes
      such as terthiophene have been shown to have anti-tumor effects on several cancer
      cell lines, including ovarian cancer cells. However, the underlying mechanisms
      behind the anti-proliferative effect of thiophenes are poorly understood. In this
      study, we investigated the molecular mechanisms underlying the anti-proliferative
      effect of alpha-terthienylmethanol, a terthiophene isolated from Eclipta
      prostrata (False Daisy), on human ovarian cancer cells. We found that alpha
      terthienylmethanol is a more potent inhibitor of cell growth than is cisplatin in
      human ovarian cancer cells. alpha-Terthienylmethanol induces cell cycle arrest in
      ovarian cancer cells, as shown by the accumulation of cells in S phase. In
      addition, alpha-terthienylmethanol induced a change in S phase-related proteins
      cyclin A, cyclin-dependent kinase 2, and cyclin D2. Knockdown of cyclin A using
      specific siRNAs significantly compromised alpha-terthienylmethanol-induced S
      phase arrest. We further demonstrated that alpha-terthienylmethanol induced an
      increase in intracellular ROS, and the antioxidant N-acetyl-l-cysteine
      significantly reversed the S phase arrest induced by alpha-terthienylmethanol.
      Moreover, alpha-terthienylmethanol significantly increased the levels of p-H2AX,
      a DNA damage marker. These results suggest that alpha-terthienylmethanol inhibits
      the growth of human ovarian cancer cells by S phase cell cycle arrest via
      induction of ROS stress and DNA damage.

PMID- 28506553
TI  - Inhibition of 12/15-LO ameliorates CVB3-induced myocarditis by activating Nrf2.
AB  - Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated
      and involved in the development of heart failure. Nuclear factor E2-related
      factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to
      oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and
      its underlying molecular mechanism have not yet been elucidated. Here, we
      demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in
      coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes. Baicalein, the
      specific inhibitor of 12/15-LO, was employed to investigate the role of 12/15-LO
      and its underlying mechanism in VMC. We found that baicalein treatment alleviated
      CVB3-induced VMC mouse models, as demonstrated by less inflammatory lesions in
      the heart tissues and less CK-MB level. Moreover, baicalein treatment attenuated
      CVB3-induced inflammatory cytokine production and oxidative stress. Mechanistic
      analysis suggested that baicalein treatment relieved CVB3-induced reduction of
      Nrf2 and heme oxygenase-1 (HO-1) expressions. Taken together, our study indicated
      that inhibition of 12/15-LO ameliorates VMC by activating Nrf2, providing a new
      therapeutic strategy for the therapy of VMC.

PMID- 28506554
TI  - Selective dopamine receptor 4 activation mediates the hippocampal neuronal
      calcium response via IP3 and ryanodine receptors.
AB  - Intracellular calcium is a key factor in most cellular processes, including cell
      growth, differentiation, proliferation and neurotransmitter release. Dopamine
      (DA) mediates synaptic transmission by regulating the intracellular calcium
      content. It is not clear, however, which specific subunit of the DA receptor
      contributes to DA modulation of intracellular calcium content changes. Through
      the traditional technique of Fura-2 calcium imaging, this study demonstrated that
      the DA can induce transient calcium in cultured hippocampal neurons and that this
      response can be mimicked by a selective dopamine receptor 4 (DR4) agonist
      PD168077 (PD). PD-induced calcium transience can be blocked by a calcium
      chelator, such as BAPTA-AM, or by pre-treatment of neurons with thapsigargin, a
      IP3 receptor antagonist, or a micromolar concentration of ryanodine, a ryanodine
      receptor (RyR) antagonist. However PD-induced calcium transience cannot be
      blocked by pre-treatment of neurons with a free-calcium medium or a cocktail of
      NMDA receptor, L-type calcium channel and alpha7 nicotinic acetylcholine receptor
      blockers. These results indicate that the calcium response induced by DR4
      activation is mainly through activation of IP3 receptor in internal stores, which
      is likely to contribute to the DA modulation of synaptic transmission and
      cognitive function.

PMID- 28506555
TI  - Gut microbiota in Parkinson disease in a northern German cohort.
AB  - Pathologic and epidemiologic studies suggest that Parkinson disease (PD) may in
      some cases start in the enteric nervous system and spread via the vagal nerve to
      the brainstem. Mounting evidence suggests that the gut microbiome plays an
      important role in the communication between gut and brain and that alteration of
      the gut microbiome is involved in the pathogenesis of numerous diseases,
      including Parkinson disease. The aim of this study was to determine whether
      Parkinson disease is associated with qualitative or quantitative changes in the
      gut microbiome. We analyzed the gut microbiome in 29 PD cases and 29 age-matched
      controls by next-generation-sequencing of the 16S rRNA gene and compared
      diversity indices and bacterial abundances between cases and controls. Alpha
      diversity measures and the abundance of major phyla did not differ between cases
      and controls. Beta diversity analyses and analysis on the bacterial family level
      revealed significant differences between cases and controls for four bacterial
      families. In keeping with recently published studies, Lactobacillaceae were more
      abundant in cases. Barnesiellaceae and Enterococcacea were also more abundant in
      cases in this study but not in other studies. Larger studies, accounting for drug
      effects and further functional investigations of the gut microbiome are necessary
      to delineate the role of the gut microbiome in the pathogenesis of PD.

PMID- 28506556
TI  - Pfizer to make palbociclib temporarily free on NHS.

PMID- 28506558
TI  - Switch to exemestane effective in early breast cancer.

PMID- 28506557
TI  - Brigatinib effective in ALK-positive non-small-cell lung cancer.

PMID- 28506559
TI  - A novel electron mirror pulse compressor.
AB  - An electron mirror-based pulse compressor design has been developed for improving
      the temporal resolution of dynamic/ultrafast transmission electron microscopes
      and ultrafast electron diffraction cameras. The improvement will enable electron
      microscopes and diffraction cameras to better resolve the dynamics of reactions
      in the areas of solid state physics, chemistry, and biology. The design utilizes
      a combination of mirror optics and a magnetic beam separator, which exploits the
      symmetry inherent in reversing the electron trajectory in the mirror in order to
      compress the pulse. This system can also simultaneously correct the spherical and
      chromatic aberration of the objective lens for improved spatial resolution. For
      pulsed experiments with a practical bunch charge, the correction of the chromatic
      aberration coefficient counters the spread in the electron energies induced by
      the space charge of the pulse to make possible the probing of the sample with
      high spatial resolution. The pulse compressor can accommodate pulses with a range
      of electron densities and energy spreads. Furthermore, it is designed to fit into
      both ultrafast electron diffraction cameras and dynamic/ultrafast transmission
      electron microscopes. Consequently, this instrument is suitable for enhancing the
      study of the structure, composition, and bonding states of new materials at
      ultrafast time scales.

PMID- 28506560
TI  - A Rare Clinical Entity in Bladder Cancer: Paraneoplastic Cerebellar Degeneration.

PMID- 28506561
TI  - The Consequences of Real Life Practice of Early Abdominal Aortic Aneurysm Repair:
      A Cost-Benefit Analysis.
AB  - BACKGROUND: The reported 54 mm median intervention diameter for endovascular
      aneurysm repair (EVAR) in the Vascular Quality Initiative and European data from
      the Pharmaceutical Aneurysm Stabilisation Trial (PHAST) implies that in real life
      the majority of abdominal aortic aneurysm (AAA) repairs occur at diameters
      smaller than the consensus intervention threshold of 55 mm. This study explores
      the potential consequences of this practice. METHODS: The differences between
      real life AAA repair and consensus based intervention threshold were explored in
      reported data from vascular quality initiatives and PHAST. The subsequent
      consequences of advancement of endovascular aneurysm repair (EVAR) were estimated
      using a multistate model based on life tables for the EVAR Medicare population.
      RESULTS: There appears an approximate 5 mm difference in AAA diameter between
      real life practice and consensus intervention threshold. Assuming a 2.5 mm annual
      growth rate, this results in an approximately 2 year advancement of AAA repair.
      According to the model used, early repair reduces overall small aneurysm patient
      mortality by 2.3%, it results in 21.9% more EVAR procedures, more EVAR related
      deaths, and 42.3% and 36.8% more open and endovascular re-interventions,
      respectively. Cost-benefit estimates imply 482 fewer AAA related deaths, but 140
      extra EVAR related deaths for a population of more than 30,000 AAA patients, and
      a 300 million USD increase in health costs for the 8 year observation period in
      the Medicare population. CONCLUSIONS: In the real life situation a large
      proportion of EVAR procedures appear to occur before reaching the consensus
      threshold. Although this reduces mortality, it comes at a cost of approximately 1
      million USD per prevented rupture related death.

PMID- 28506562
TI  - The Impact of System Factors on Quality and Safety in Arterial Surgery: A
      Systematic Review.
AB  - OBJECTIVE: A systems approach to patient safety proposes that a wide range of
      factors contribute to surgical outcome, yet the impact of team, work environment,
      and organisational factors, is not fully understood in arterial surgery. The aim
      of this systematic review is to summarize and discuss what is already known about
      the impact of system factors on quality and safety in arterial surgery. DATA
      SOURCES: A systematic review of original research papers in English using
      MEDLINE, Embase, PsycINFO, and Cochrane databases, was performed according to
      PRISMA guidelines. REVIEW METHODS: Independent reviewers selected papers
      according to strict inclusion and exclusion criteria, and using predefined data
      fields, extracted relevant data on team, work environment, and organisational
      factors, and measures of quality and/or safety, in arterial procedures. RESULTS:
      Twelve papers met the selection criteria. Study endpoints were not consistent
      between papers, and most failed to report their clinical significance. A variety
      of tools were used to measure team skills in five papers; only one paper measured
      the relationship between team factors and patient outcomes. Two papers reported
      that equipment failures were common and had a significant impact on operating
      room efficiency. The influence of hospital characteristics on failure-to-rescue
      rates was tested in one large study, although their conclusions were limited to
      the American Medicare population. Five papers implemented changes in the patient
      pathway, but most studies failed to account for potential confounding variables.
      CONCLUSIONS: A small number of heterogenous studies have evaluated the
      relationship between system factors and quality or safety in arterial surgery.
      There is some evidence of an association between system factors and patient
      outcomes, but there is more work to be done to fully understand this
      relationship. Future research would benefit from consistency in definitions, the
      use of validated assessment tools, measurement of clinically relevant endpoints,
      and adherence to national reporting guidelines.

PMID- 28506563
TI  - Challenges to delivery and effectiveness of adjuvant radiation therapy in elderly
      patients with node-positive vulvar cancer.
AB  - OBJECTIVE: To examine adjuvant radiation therapy (RT) use, patterns of RT
      delivery, and clinical outcomes in older patients with node-positive vulvar
      cancer. METHODS: Using SEER-Medicare linked data, we identified 444 patients
      (age>=66years) with node-positive squamous cell vulvar carcinoma, without distant
      metastases, and treated with primary surgery between 1991 and 2009. We used
      claims to examine RT use and the following delivery metrics: 1) completion of
      >=20 fractions, 2) treatment duration <8weeks, 3) <1week of intra-treatment
      break, and 4) treatment interval from surgery to start of RT <8weeks. We tested
      associations between RT use and metrics with overall (OS) and cause-specific
      survival (CSS) using multivariate proportional hazards regression. RESULTS:
      Median age was 78years (interquartile range [IQR]=74-83). Median follow-up was
      17months (IQR=9-40). Three hundred six patients (69%) received RT. Three delivery
      metrics were associated with improved outcomes: completion of >=20 fractions,
      treatment duration <8weeks, and <1week of intra-treatment break. Patients who
      achieved these 3 metrics demonstrated better disease outcomes compared with
      surgery alone (OS hazard ratio [HR] for death=0.62, 95% confidence interval
      [CI]=0.46-0.82, P=0.001; CSS HR=0.58, 95% CI=0.40-0.85,P=0.005). Patients not
      achieving RT metrics demonstrated marginal improvements in disease outcomes over
      surgery alone (OS HR=0.73, 95% CI=0.55-0.99,P=0.04; CSS HR=0.76, 95% CI=0.52
      1.11, P=0.16). Notably, only 51% of patients who received RT achieved all
      benchmarks. CONCLUSIONS: In this cohort of older women with node-positive vulvar
      cancer, achieving metrics for RT delivery was an important factor for optimizing
      disease benefits from treatment.

PMID- 28506564
TI  - Contamination of cockroaches (Insecta: Blattaria) to medically fungi: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: Fungal infections have emerged worldwide. Cockroaches have been
      proved vectors of medically fungi. METHODS: A systematic meta-analysis review
      about cockroach fungal contamination was investigated. Relevant topics were
      collected between January 2016 and January 2017. After a preliminary review among
      392 collected papers, 156 were selected to become part of the detailed systematic
      meta-analysis review. RESULTS: Cockroaches contaminated to 38 fungi species
      belonging to 19 families and 12 orders. About 38, 25 and 13 fungal species were
      recovered from the American, German and brown-banded cockroaches, respectively
      with a variety of medical importance. Except the fungi isolated from German and
      brown-banded cockroaches, 15 species have been isolated only from the American
      cockroaches. The global world mean and trend of cockroach fungal contamination
      were 84.1 and 50.6-100%, respectively in the human dwelling environments. There
      is a significant difference between cockroach fungal contamination in the urban
      and rural environments (P<0.05) without a significant difference between hospital
      and household environments (P>0.05). The external and internal cockroach fungal
      contamination is more dangerous than entire surfaces, while the internal is more
      dangerous than the external surface. The German and brown-banded cockroach fungal
      contamination are more dangerous than the American cockroaches in the hospital
      environments. CONCLUSION: The study indicates that globally cockroach fungal
      contamination has been increased recognizing as agents of human infections and
      associating with high morbidity and mortality in immune-compromised patients.
      These facts, along with insecticide resistance emergence and increasing globally
      cockroach infestation, reveal importance of cockroaches and need for their
      control more than ever.

PMID- 28506565
TI  - The antifungal activity of Moroccan plants and the mechanism of action of
      secondary metabolites from plants.
AB  - This review is based on a comprehensive literature search for existing knowledge
      about antifungal mechanisms of different secondary metabolites from plants. The
      secondary metabolites have been grouped into three major groups according to
      their biosynthetic origin. On another side, this review represents studies on
      antifungal activity of essential oils and extracts from Moroccan plants, against
      fungal species involved in human or plant diseases.

PMID- 28506566
TI  - Trends in racial/ethnic disparities of new AIDS diagnoses in the United States,
      1984-2013.
AB  - PURPOSE: In the United States, human immunodeficiency virus (HIV)/acquired immune
      deficiency syndrome (AIDS) disproportionately impacts racial/ethnic minorities.
      We describe and evaluate trends in the Black-White and Hispanic-White disparities
      of new AIDS diagnoses from 1984 to 2013 in the United States. METHODS: AIDS
      diagnosis rates by race/ethnicity for people >=13 years were calculated using
      national HIV surveillance and Census data. Black-White and Hispanic-White
      disparities were measured as rate ratios. Joinpoint Regression was used to
      identify time periods across which to estimate rate-ratio trends. We calculated
      the estimated annual percent change in disparities for each time period using log
      normal linear regression modeling. RESULTS: Black-White disparity increased from
      1984 to 1990, followed by a large increase from 1991 to 1996, and a smaller
      increase from 1997 to 2001. Black-White disparity moderated from 2002 to 2005 and
      rose again from 2006 to 2013. Hispanic-White disparity increased from 1984 to
      1997 but declined after 1998. Black-White and Hispanic-White disparities
      increased for men who have sex with men during 2008 to 2013. CONCLUSIONS: Recent
      increases in racial/ethnic disparities of AIDS diagnoses were observed and may be
      due in part to care continuum inequalities. We suggest assessing disparities in
      AIDS diagnoses as a high-level measure to capture changes at multiple stages of
      the care continuum collectively. Future research should examine determinants of
      racial/ethnic differences at each step of the continuum to better identify
      characteristics driving disparities.

PMID- 28506567
TI  - The impact of walk-in centres and GP co-operatives on emergency department
      presentations: A systematic review of the literature.
AB  - BACKGROUND: Internationally, non-urgent presentations are increasing the pressure
      on Emergency Department (ED) staff and resources. This systematic review aims to
      identify the impact of alternative emergency care pathways on ED presentations -
      specifically GP cooperatives and walk-in clinics. METHODS: Based on a structured
      PICO enquiry with either walk-in clinic or GP cooperative as the intervention, a
      search was made for peer-reviewed publications in English, between 2000 and 2014.
      Medline plus, OVID, PubMed, and Google Scholar were searched. The Critical
      Appraisal Skills Program (CASP) guidelines were used to assess study quality and
      data was extracted using an adapted JBI Qualitative Assessment and Review
      Instrument (QARI). Subsequent reporting followed the PRISMA guideline. RESULTS:
      Eleven high quality quantitative studies met the inclusion criteria. Walk-in
      clinics do have the potential to reduce non-urgent emergency department
      presentations, however evidence of this effect is low. GP cooperatives offer an
      alternative care stream for patients presenting to the ED and do significantly
      reduce local ED attendances. Community members need to be made aware of these
      options in order to make informed treatment choices. CONCLUSION: GP cooperatives
      in particular do have the potential to reduce ED workload. Further research is
      required to uncover recent trends and patient outcomes for walk-in clinics and GP
      cooperatives.

PMID- 28506568
TI  - Adverse pathologic features in early oral squamous cell carcinoma and the role of
      postoperative radiotherapy-a review.
AB  - The use of postoperative radiotherapy (PORT) in early stage oral cancer with
      adverse pathologic features (APFs) is controversial. Prognostically relevant APFs
      reviewed were perineural invasion, lymphovascular invasion, depth of invasion,
      worst pattern of invasion, and margin status. The current literature remains
      divided with regard to the benefit of treatment escalation in these patients;
      although these patients are at high risk for recurrence, the morbidity of PORT
      needs to be balanced against the likely benefit in disease control. A wide
      heterogeneity in the literature exists, likely as a result of differences in
      treatment protocols. We performed a literature review of the role of PORT in
      early-stage oral cancer with APFs. Based on the current evidence, the decision to
      administer adjuvant therapy needs to be made on an individual basis; patients
      with >1 APF are likely to benefit from PORT, and the use of risk-scoring systems
      may help in decision making.

PMID- 28506569
TI  - [Identifying potentially inappropriate prescriptions in patients over 65 years
      old using original Beers criteria and their Spanish adaptation].
AB  - OBJECTIVE: To compare the detection of potentially inappropriate medication (PIM)
      using the original Beers criteria, a global reference for evaluating
      prescriptions in the elderly, and their Spanish version. DESIGN: Retrospective
      observational study LOCATION: A Primary Care area in the province of Murcia,
      Spain. PARTICIPANTS: A total of 7,856 subjects aged 65 and over, with at least
      one drug prescribed in a Primary Care Area of Spain during study period. METHOD:
      Illnesses and treatments registered in the Primary Care computerised medical
      history of patients were analysed during a 12month study period (2012). The
      original Beers criteria and their Spanish adaptation were used to evaluate PIM,
      considering both sets of criteria overall, and individually. RESULTS: The median
      age of the patients was 76.0years, with the majority females (56.6%). Patients
      received a median of 13 active substances and 66 medical prescriptions. The
      percentage of patients prescribed PIM ranged from 44.8% according to the original
      Beers criteria to 49.4% with the Spanish adaptation. CONCLUSIONS: PIMs are
      frequent in our context. The original Beers criteria, if not adapted to the local
      drug catalogue, underestimated the frequency of PIM in the elderly population
      studied.

PMID- 28506570
TI  - The local liver ablation with pulsed electric field stimulate systemic immune
      reaction against hepatocellular carcinoma (HCC) with time-dependent cytokine
      profile.
AB  - AIM: How irreversible electroporation (IRE) affect immune status is still kept
      unknown. This preclinical study is to investigate its local and systemic immune
      reaction both on tumor-bearing and tumor free animals. METHODS: Liver ablation
      was performed by a standard IRE instrument and proposal. Altogether 57 tumor
      bearing mice and 10 tumor-free porcine livers were ablated. The reaction of
      survival, radiology image, pathologically and immunologically were followed up.
      The detailed cytokines and chemokines responses were recorded dynamically post
      IRE ablation. RESULTS: IRE ablation induced coagulation and necrosis in liver. It
      caused macrophages infiltration, in ablation zone. IRE ablation caused cellular
      inflammation. It, corrected the abnormal drifted Th2 in HCC back to Th1 status,
      promoting tumor eradication and host survival. The quantified cytokines and
      chemokines indicate IRE can stimulate both local immune reaction and systemic
      immune reaction. CONCLUSION: Local IRE ablation changes the abnormal drifted Th2
      in HCC back to Th1 status, facilitating tumor eradication and host survival.

PMID- 28506571
TI  - Tumor necrosis factor receptor-associated factor (TRAF) 6 inhibition mitigates
      the pro-inflammatory roles and proliferation of rheumatoid arthritis fibroblast
      like synoviocytes.
AB  - BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a
      crucial role in RA through producing inflammatory cytokines and proteases which
      could cause cartilage destruction. We showed previously that elevated expression
      of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium
      correlated significantly with the severity of synovitis and the number of
      infiltrated inflammatory cells. The aims of this study are to detect the roles of
      TRAF6 in RA-FLSs. METHODS: Synovium were collected by closed needle biopsy from
      inflamed knees of active RA patients, and FLSs were isolated by modified tissue
      culture method. Expression of TRAF6 and CD55 in RA synivium was tested by double
      immunofluorescence (IF) staining. TRAF6 in RA-FLSs was inhibited using Lentiviral
      TRAF6-shRNA transfection. Real-time PCR and ELISA were used to detect the mRNA
      expression and secretion of matrix metalloproteinase (MMP) and pro-inflammatory
      cytokines. Cell Counting Kit-8 was used to detect cell proliferation, flow
      cytometry was used to detect cell cycle, and Annexin V assay was used to detect
      cell apoptosis. RESULTS: We showed that in the intimal and subintimal area of RA
      synovium, TRAF6 was expressed obviously not only in CD55+ cells, but also in some
      other CD55- cells. TRAF6 expression in RA-FLSs was suppressed effectively by
      Lentiviral-TRAF6-shRNA transfection. Inhibition of TRAF6 in RA-FLSs mitigated the
      mRNA levels and secretion of pro-inflammatory cytokines and MMPs, such as IL
      1beta, IL-8, IL-6, TNF-alpha, MMP-13, and MMP-3. In addition, it decreased the
      proliferation of RA-FLSs, blocked RA-FLSs in G0/G1-phase, and inhibited the cells
      to go into S-phase and G2/M-phase, but not facilitated apoptosis of RA-FLSs.
      CONCLUSION: TRAF6 plays direct roles in the pro-inflammatory effects and
      proliferation of RA-FLSs. TRAF6 may serve as a potential treatment target in RA.

PMID- 28506572
TI  - Inflammatory cytokines and oxidative stress biomarkers in irritable bowel
      syndrome: Association with digestive symptoms and quality of life.
AB  - A growing body of evidence suggests a possible role for low-grade inflammation in
      the pathogenesis of irritable bowel syndrome (IBS). The objectives of this study
      were to measure serum levels of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-17, interleukin (IL)-10, malondialdehyde (MDA) and total antioxidant
      capacity (TAC) in IBS patients and healthy controls (HCs), and to evaluate
      possible correlations of such markers with gastrointestinal (GI) symptoms and
      quality of life (QoL). Ninety Rome III positive IBS patients and 90 sex and age
      matched HCs were recruited. GI symptoms, IBS-QoL, IBS severity score system
      (IBSSS), and the serum levels of inflammatory cytokines and oxidative stress
      biomarkers were evaluated. In IBS patients, TNFalpha, IL-17 and MDA cytokines
      were significantly (P<0.05) higher, and IL-10 cytokine and TAC were significantly
      (P<0.05) lower vs. HCs. When comparing IBS subtypes, TNFalpha and IL-17 were
      significantly (P<0.05) higher, and IL-10 was significantly (P<0.05) lower in
      diarrhea predominant IBS (IBS-D) compared to HCs, whereas the inflammatory
      cytokine profile of other subtypes more closely resembled that of HCs. The serum
      levels of MDA and TAC were significantly different (P<0.05) in all the subtypes
      vs. HCs. All the inflammatory cytokines had significant (P<0.05) correlations
      with GI symptoms, IBSSS and IBS-QoL, whereas no significant association was found
      between oxidative stress biomarkers and these symptoms. IBS-D patients display
      increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines.
      Present study demonstrated a correlation between inflammatory cytokines and both
      IBS symptoms and QoL.

PMID- 28506573
TI  - Nanogenerators for Human Body Energy Harvesting.
AB  - Humans generate remarkable quantities of energy while performing daily
      activities, but this energy usually dissipates into the environment. Here, we
      address recent progress in the development of nanogenerators (NGs): devices that
      are able to harvest such body-produced biomechanical and thermal energies by
      exploiting piezoelectric, triboelectric, and thermoelectric physical effects. In
      designing NGs, the end-user's comfort is a primary concern. Therefore, we focus
      on recently developed materials giving flexibility and stretchability to NGs. In
      addition, we summarize common fabrics for NG design. Finally, the mid-2020s
      market forecasts for these promising technologies highlight the potential for the
      commercialization of NGs because they may help contribute to the route of
      innovation for developing self-powered systems.

PMID- 28506574
TI  - The degree of integration of non-dispensing pharmacists in primary care practice
      and the impact on health outcomes: A systematic review.
AB  - BACKGROUND: A non-dispensing pharmacist conducts clinical pharmacy services aimed
      at optimizing patients individual pharmacotherapy. Embedding a non-dispensing
      pharmacist in primary care practice enables collaboration, probably enhancing
      patient care. The degree of integration of non-dispensing pharmacists into
      multidisciplinary health care teams varies strongly between settings. The degree
      of integration may be a determinant for its success. OBJECTIVES: This study
      investigates how the degree of integration of a non-dispensing pharmacist impacts
      medication related health outcomes in primary care. METHODS: In this literature
      review we searched two electronic databases and the reference list of published
      literature reviews for studies about clinical pharmacy services performed by non
      dispensing pharmacists physically co-located in primary care practice. We
      assessed the degree of integration via key dimensions of integration based on the
      conceptual framework of Walshe and Smith. We included English language studies of
      any design that had a control group or baseline comparison published from 1966 to
      June 2016. Descriptive statistics were used to correlate the degree of
      integration to health outcomes. The analysis was stratified for disease-specific
      and patient-centered clinical pharmacy services. RESULTS: Eighty-nine health
      outcomes in 60 comparative studies contributed to the analysis. The accumulated
      evidence from these studies shows no impact of the degree of integration of non
      dispensing pharmacists on health outcomes. For disease specific clinical pharmacy
      services the percentage of improved health outcomes for none, partial and fully
      integrated NDPs is respectively 75%, 63% and 59%. For patient-centered clinical
      pharmacy services the percentage of improved health outcomes for none, partial
      and fully integrated NDPs is respectively 55%, 57% and 70%. CONCLUSIONS: Full
      integration adds value to patient-centered clinical pharmacy services, but not to
      disease-specific clinical pharmacy services. To obtain maximum benefits of
      clinical pharmacy services for patients with multiple medications and
      comorbidities, full integration of non-dispensing pharmacists should be promoted.

PMID- 28506575
TI  - [Therapeutic education in primary cardiovascular prevention: 4 years sustained
      interest].
AB  - BACKGROUND: Our patient therapeutic education program yields improvements in
      health after one year. But what can we see after 4 years, when the patient alone
      is responsible for following the program? PATIENTS AND METHODS: Two hundred and
      ninety-one patients participated in the first part of our study and were followed
      during one year. Four years into the ongoing study, we reviewed the progress of
      the first 200 patients. We compared the already published Risk Factors and Eating
      Habits scores between the beginning of the study (T0), one year later (T1) and
      after 4 years (T4). RESULTS: The Risk Factor score at T0 is 9.5+/-7.8, moving to
      7+/-7.5 at T1, and then to 6.8+/-7.8 at T4 (P<0.001 between T0 and T1 and T0 and
      T4). Endurance physical activities saw the greatest improvement: 0.79+/-5 at T0, 
      1.07+/-4.5 at T1 and -1.61+/-4.5 at T4 (P<0.001 between T0 and T1 and T0 and T4).
      The Eating Habits score went from -18.2+/-7.3 to -22.2+/-6.4 and then to -23.5+/
      6.4 (P<0.001 between T0 and T1 and T0 and T4). The best results were obtained
      through increased consumption of whole grains, green vegetables and fish.
      CONCLUSION: The positive results of the progress of risk factors and eating
      habits, noted after one year, are even greater four years after the end of the
      therapeutic education program.

PMID- 28506576
TI  - [Clinical characteristics and follow-up of patients with magnetic resonance
      imaging confirmed myopericarditis: A retrospective study].
AB  - INTRODUCTION: Pericarditis are frequently associated with some degree of
      concomitant myocardial involvement. Predominant pericarditis with limited
      myocardial involvement are named myopericarditis. Data regarding myopericarditis
      are scarce. PATIENTS AND METHODS: Retrospective chart review of all patients
      admitted between 2002 and 2011 with magnetic resonance imaging confirmed
      myopericarditis. RESULTS: Twenty-seven patients were included. Eighty-one percent
      were men, with median age of 32 years. Infectious disease preceded
      hospitalization in 55% of cases. Mean left ventricle ejection fraction at
      admission was 55% with focal myocardial impairment mainly localized in lateral
      and inferior walls. Coronary angiogram was performed in 37% of cases to rule out
      an ischaemic aetiology. We identified 5 cases (19%) of myopericarditis preceded
      by an episode of streptococcus group A throat infection. Non-sustained
      ventricular tachycardia was observed in 15% of cases. After a 2-year follow-up
      period, mortality rate was zero and recurrence rate was 15%. CONCLUSIONS: In our
      series, myopericarditis was a benign disease affecting mostly young men, and
      prognosis was good. A significant proportion of cases was preceded by group A
      streptococcus infection.

PMID- 28506577
TI  - [Oral anticoagulants adherence in elderly patients treated for atrial
      fibrillation in the era of direct oral anticoagulants].
AB  - BACKGROUND: The aim of this study was to determine the level of adherence to oral
      anticoagulants in the population of elderly patients treated for a non-valvular
      atrial fibrillation (AF) in the era of direct oral anticoagulants. PATIENTS AND
      METHOD: This transversal study used Morisky scale to assess adherence to oral
      anticoagulants. We also collected patients' reviews about the treatment and
      factors explaining a poor adherence. RESULTS: Between January and June 2015, 64
      patients were included in Loire Atlantique. Average age was 77.8 years, CHA2DS2
      VASc score was 4.06 and treatment (vitamin K antagonists [VKAs] in 78% patients)
      was prescribed since 4.3 years. According to Morisky scale, 84.4% of patients had
      a good adherence. There was 88% of good adherence with AVK versus 71% with direct
      oral anticoagulant, there was no statistically significant difference. The
      prescriber and the knowledge of anticoagulant treatment role seemed to be
      determinant factors. CONCLUSIONS: The level of adherence for oral anticoagulant
      appears higher than in most published studies. Diversification of therapeutic
      options could constitute an aid to personalize the prescription in order to
      improve it.

PMID- 28506578
TI  - [Congenital heart disease in adolescents and adults: Management in a general
      cardiology department in Senegal].
AB  - BACKGROUND: Congenital heart diseases in adults include malformations treated in
      childhood that decompensate secondarily and those asymptomatic at birth, appear
      later. This study aims to identify congenital heart diseases in adults in general
      cardiology department of Senegal and to assess clinical presentations, treatment
      and outcomes. METHODS: We conducted a cross-sectional and descriptive study based
      on the records of patients aged at least 16 years and followed for congenital
      heart disease in the cardiology department of the General Hospital of Grand-Yoff
      in Dakar between May 2003 and March 2015. Diagnosis of heart disease was based on
      echocardiography. RESULTS: We have registered 50 dossiers of patients equivalent
      to a prevalence of 0.75%, with a female predominance (64%). The average age of
      patients was 36.2+/-18.4 years (16-79 years), and mean age of diagnosis was
      29.76+/-22.58 years. Dyspnea was the main sign (60%). Main malformations were the
      atrial septal defect (38%), pulmonary stenosis (14%), the ventricular septal
      defect (12%) and patent ductus arteriosus (10%). According to the classification
      of Bethesda, heart disease was simple complexity (42%), intermediate (58%) or
      severe (10%). The treatment was medical in 43 patients and 7 patients had
      surgical repair. Main complications were infective endocarditis (10%), atrial
      fibrillation (12%), heart failure (24%) and pulmonary arterial hypertension
      (50%). CONCLUSION: Congenital heart diseases in adults seem underestimated in our
      countries. Surgical repair is rare. It is necessary to ensure a good management
      of the transition between pediatric and adult age.

PMID- 28506579
TI  - [Initial management of ST-elevation myocardial infarction in 2014: From
      guidelines to practices, survey of 176 French interventional cardiologists].
AB  - BACKGROUND: Real life management of myocardial infarction has not recently been
      evaluated in France. AIMS: To describe ST-elevation myocardial infarction
      management in France in 2014 and to compare it with current guidelines. METHODS:
      A multicentre study was performed. An e-mail questionnaire was sent to French
      interventional cardiologists. Demographic data of interventional cardiologists,
      procedural aspects of percutaneous coronary intervention, antithrombotic
      treatments and patient rehabilitation have been investigated. RESULTS: One
      hundred and seventy-six answers were analysed. Most of centres realized more than
      600 annual angioplasties. An average of 209 myocardial infarctions were managed
      per centre in 2014, more often in academic than in general or private centres
      (respectively 51, 32 and 17% of infarctions). Anti-GPIIbIIIa (34% of the cases)
      and thromboaspiration were not systematic but depend on patient's
      characteristics, according to guidelines. Radial access was favoured in 85% of
      the cases and increased for the last decade. Drug eluting stents were used in 62%
      of cases. Unfractionated heparin and enoxaparine accounted for more than 80% of
      anticoagulants treatments. Overall, use of clopidogrel was as high as that of
      prasugrel or ticagrelor although clopidogrel is recommended in second-line.
      Cardiovascular rehabilitation was proposed to more than 50% of patients.
      CONCLUSION: In spite of heterogeneity of ST-elevation myocardial infarction
      management in 2014, real-life practices generally comply with current guidelines.

PMID- 28506580
TI  - [Hyponatremic-hypertensive syndrome successfully treated by endovascular therapy:
      A case report].
AB  - INTRODUCTION: Hyponatremic-hypertensive syndrome (HHS) is characterized by
      hypertension and hyponatremia. CASE PRESENTATION: We report a case of HHS in a 73
      year-old woman, revealed by a hyponatremia leading to status epilepticus, without
      initial hypertension due to hypovolemia. She was successfully treated by
      endovascular therapy without any long-term supplementation or anti-hypertensive
      medication. CONCLUSION: Physiopathology hypothesis of HHS implicate pressure
      natriuresis, in this case, hypertension is not initially found and we discuss
      other hyponatremia mechanisms.

PMID- 28506581
TI  - [Sudden death in Versailles: A review of a cardiovascular treatrise by Dionis
      (1710)].
AB  - In 1710, the surgeon Pierre Dionis publishes a Dissertation on sudden death.
      Echoing and expanding the work of his Roman colleague Jean Marie Lancisi, he
      describes and analyzes dozens of cases of sudden death observed by him. A large
      number of cases was followed by autopsies allowing clinicopathological
      confrontation. Are proposed causes of death (pulmonary embolism, myocardial
      infarction, hemorrhagic stroke, arterial rupture, etc.), pathophysiological
      mechanisms based on the ancient theory of humors, and preventive actions to avoid
      these unexpected deaths. In this article, we oppose these old data to those of
      current literature.

PMID- 28506582
TI  - Dual functional small molecule fluorescent probes for image-guided estrogen
      receptor-specific targeting coupled potent antiproliferative potency for breast
      cancer therapy.
AB  - A strategy by integrating biological imaging into early stages of the drug
      discovery process can improve our understanding of drug activity during
      preclinical and clinical study. In this article, we designed and synthesized
      coumarin-based nonsteroidal type fluorescence ligands for drug-target binding
      imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER
      binding affinity and 3e (IC50=0.012MUM) exhibited excellent ERalpha antagonistic
      activity, its antiproliferative potency in breast cancer MCF-7 cells is
      equipotent to the approved drug tamoxifen. The fluorescence of compounds 3e and
      3f depended on the solvent properties and showed significant changes when mixed
      with ERalpha or ERbeta in vitro. Furthermore, target molecule 3e could cross the
      cell membrane, localize and image drug-target interaction in real time without
      cell washing. Thus, the coumarin-based platform represents a promising new ER
      targeted delivery vehicle with potential imaging and therapeutic properties.

PMID- 28506583
TI  - Synthesis of enantiomerically enriched drug precursors and an insect pheromone
      via reduction of ketones using commercially available carbonyl reductase
      screening kit "Chiralscreen(r) OH".
AB  - Commercially available "Chiralscreen(r) OH" starter kit containing five types of
      carbonyl reductases (E001, E007, E031, E039, and E078) was used for the reduction
      of several aromatic and aliphatic ketones to obtain enantiomerically enriched
      drug precursors and an insect pheromone. Almost stereochemically pure secondary
      alcohols, used in the synthesis of drugs such as (R)-rasagiline mesylate, (S)
      rivastigmine, (R)-chlorphenesin carbamate, and (R)-mexiletine, and the insect
      pheromone (4S,5R)-sitophilure, were conveniently obtained. The enzymes worked
      well with ketones containing at least one non-bulky substituent at the carbonyl
      group. The diverse stereochemical preference of the above five carbonyl
      reductases was clarified.

PMID- 28506584
TI  - Development of nonsteroidal glucocorticoid receptor modulators based on N-benzyl
      N-(4-phenoxyphenyl)benzenesulfonamide scaffold.
AB  - N-Benzyl-N-(4-phenoxyphenyl)benzenesulfonamide derivatives were developed as a
      novel class of nonsteroidal glucocorticoid receptor (GR) modulators, which are
      promising drug candidates for treating immune-related disorders. Focusing on the
      similarity of the GR and progesterone receptor (PR) ligand-binding domain (LBD)
      structures, we adopted our recently developed PR antagonist 10 as a lead compound
      and synthesized a series of derivatives. We found that the N-(4
      phenoxyphenyl)benzenesulfonamide skeleton serves as a versatile scaffold for GR
      antagonists. Among them, 4-cyano derivative 14m was the most potent, with an IC50
      value of 1.43MUM for GR. This compound showed good selectivity for GR; it
      retained relatively weak antagonistic activity toward PR (IC50 for PR: 8.00MUM;
      250-fold less potent than 10), but showed no activity toward AR, ERalpha or
      ERbeta. Interestingly, the 4-amino derivative 15a exhibited transrepression
      activity toward NF-kappaB in addition to GR-antagonistic activity, whereas 14m
      did not. The structure-activity relationship for transrepression was different
      from that for GR-antagonistic activity. Computational docking simulations
      suggested that 15a might bind to the ligand-binding pocket of GR in a different
      manner from 14m. These findings open up new possibilities for developing novel
      nonsteroidal GR modulators with distinctive activity profiles.

PMID- 28506585
TI  - C21-steroidal pregnane sapogenins and their derivatives as anti-inflammatory
      agents.
AB  - During the screening of natural anti-inflammatory agent, we identified some C21
      steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4
      initiatedinflammatory responses respectively. Treatment with active compounds 10,
      2j and 3p failed to impact tumor necrosis factor-alpha (TNF-alpha) induced
      nucleus translocation of NF-kappaB p65 subunit. However, these compounds
      regulated distinct canonical or non-canonical NF-kappaB family members. Ectopic
      expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory
      activity of the compounds on production of pro-inflammatory cytokines downstream
      of TLR4. These results suggested that compounds 10, 2j, and 3p suppressed TLR
      initiated innate immunity through TRAF6 with differential regulation of NF-kappaB
      family proteins.

PMID- 28506586
TI  - Corrigendum to "Airborne Asbestos Exposures Associated with Gasket and Packing
      Replacement: A Simulation Study of Flange and Valve Repair Work and an Assessment
      of Exposure Variables" [Regul. Toxicol. Pharmacol. 71 (1) (2014) 35-51].

PMID- 28506587
TI  - The Art of Feedback in Medical Practice.

PMID- 28506588
TI  - Double-balloon enteroscopy: Indications, approaches, diagnostic and therapeutic
      yield, and safety. Early experience at a single center.
AB  - INTRODUCTION AND AIMS: Double-balloon enteroscopy has been improving the
      visualization of the entire intestine for more than a decade. It is a
      complementary method in the study of intestinal diseases that enables biopsies to
      be taken and treatments to be administered. Our aim was to describe its main
      indications, insertion routes, diagnostic/therapeutic yield, and complications.
      MATERIALS AND METHODS: All patients referred to our unit with suspected small
      bowel pathology were included. The insertion route (oral/anal) was determined
      through diagnostic suspicion. The variables measured were: insertion route, small
      bowel examination extent, endoscopic diagnosis/treatment, biopsy/histopathology
      report, complications, and surgical findings. RESULTS: The study included 28
      double-balloon enteroscopies performed on 23 patients, of which 10 were women and
      13 were men (mean age of 52.95 years). The oral approach was the most widely used
      (n=21), the main indication was overt small bowel bleeding (n=16), and the
      general diagnostic yield was 65.21%. The therapeutic intervention rate was 39.1%
      and the procedure was effective in all the cases. The most widely used treatment
      was argon plasma therapy (n=7). The complication rate was 8.6%; one patient
      presented with low blood pressure due to active bleeding and another had deep
      mucosal laceration caused by the argon plasma. CONCLUSIONS: Double-balloon
      enteroscopy is a safe and efficacious method for the study and management of
      small bowel diseases, with an elevated diagnostic and therapeutic yield.

PMID- 28506589
TI  - The relationship between dosimetric factors, side effects, and survival in
      patients with non-small cell lung cancer treated with definitive radiotherapy.
AB  - The patients with non-small cell lung cancer (NSCLC) treated with definitive
      conformal radiotherapy (RT) were evaluated in terms of side effects and survival.
      Normal tissue complication probability (NTCP) was calculated for 68 patients
      treated between 2009 and 2012. Clinical and dosimetric factors were analyzed. The
      median dose of 63 Gy (range: 54 to 70 Gy) was given with conformal RT with blocks
      (n = 37), 3-dimensional conformal RT (3DCRT) (n = 11), or intensity-modulated RT
      (IMRT) (n = 20). Acute grade 1 to 2 radiation pneumonitis (RP) was seen in 13% of
      the patients. No significant relationship was found between RP and treatment and
      dosimetric factors (p > 0.05). There was a positive correlation between median
      "mean lung dose" (MLD) (17 Gy), lung V30 (20.5%), and NTCP (14%) (p < 0.001).
      Median and 2-year overall survival (OS) and progression-free survival (PFS) were
      27 and 18 months and 51% and 42%, respectively. In univariate analysis,
      significant dose range for survival was found between 59.4 and 63 Gy (p < 0.01).
      In multivariate analysis, response (p = 0.001), fraction dose of 1.8 Gy (p =
      0.002), MLD <18 Gy (p = 0.04) for OS and response (p < 0.001), total dose > 59.4
      Gy (p = 0.01), and tumor biologically effective dose (BED)3(Gy) <= 100.8 (p =
      0.01) for PFS were found to be favorable factors. In our study, we found a linear
      correlation between NTCP and MLD for RP risk estimation in patients with NSCLC.
      Therapeutic dose range where MLD can be kept under 20 Gy with significant
      survival benefit was found between 59.4 and 63 Gy. Increased therapeutic efficacy
      will be possible using risk-adaptive RT techniques.

PMID- 28506590
TI  - RNF213 p.R4810K Variant and Intracranial Arterial Stenosis or Occlusion in
      Relatives of Patients with Moyamoya Disease.
AB  - BACKGROUND: This study aimed to determine the effectiveness of genetic testing
      for the p.R4810K variant (rs112735431) of the Mysterin/RNF213 gene, which is
      associated with moyamoya disease and other intracranial vascular diseases, in the
      family members of patients with moyamoya disease. METHODS: We performed
      genotyping of the RNF213 p.R4810K polymorphism and magnetic resonance angiography
      on 59 relatives of 18 index patients with moyamoya disease. Nineteen individuals
      had follow-up magnetic resonance angiography with a mean follow-up period of 7.2
      years. RESULTS: Six of the 34 individuals with the GA genotype (heterozygotes for
      p.R4810K) showed intracranial steno-occlusive lesions in the magnetic resonance
      angiography, whereas none of the 25 individuals with the GG genotype (wild type)
      showed any abnormalities. Follow-up magnetic resonance angiography revealed de
      novo lesions in 2 and disease progression in 1 of the 11 individuals with the GA
      genotype, despite none of the 8 individuals with the GG genotype showing any
      changes. Accordingly, 8 individuals had steno-occlusive lesions at the last
      follow-up, and all had the p.R4810K risk variant. The prevalence of steno
      occlusive intracranial arterial diseases in family members with the p.R4810K
      variant was 23.5% (95% confidence interval: 9.27%-37.78%), which was
      significantly higher than in those without the variant (0%, P = .0160).
      CONCLUSIONS: Genotyping of the p.R4810K missense variant is useful for
      identifying individuals with an elevated risk for steno-occlusive intracranial
      arterial diseases in the family members of patients with moyamoya disease.

PMID- 28506591
TI  - Early Echocardiography Has a Low Yield in Patients with Transient Ischemic
      Attack.
AB  - STUDY OBJECTIVE: Current guidelines recommend patients presenting with transient
      ischemic attack (TIA) undergo echocardiography to evaluate for a cardiac source.
      However, echocardiography is not available daily at many centers. We assessed the
      yield from early transthoracic echocardiography (TTE) in consecutive patients
      with TIA evaluated in an emergency department observation unit (EDOU) protocol.
      METHODS: This observational cohort study took place in an academic medical center
      from January 1, 2011 to July 31, 2013. Patients seen in the emergency department,
      assigned to the EDOU for a TIA accelerated diagnostic protocol and discharged
      with a diagnosis of TIA were included. We retrospectively collected baseline
      patient characteristics, ABCD2 score, neuroimaging, telemetry, TTE, and 3-month
      clinical outcomes. RESULTS: Of 236 subjects (mean age 62 +/- 15 years, 68%
      female, 57% African American, 17% with history of stroke, 27% with history of
      cardiac disease, mean ABCD2 score 3.8 +/- 1.5, mean EDOU length of stay 18.6 +/-
      6.2 hours), abnormal bedside cardiac examination was identified in 19 (8%)
      patients, abnormal electrocardiogram (ECG)/telemetry in 41 (17%), and abnormal
      TTE in 64 (27%), 41 of which suggested a patent foramen ovale. Among 136 (58%)
      patients with no previous cardiac disease or stroke, a normal bedside cardiac
      examination, and normal ECG/telemetry, TTE identified no high-risk cardiac
      causes. CONCLUSION: In patients with TIA presenting to an EDOU with no previous
      cardiac disease or stroke, normal cardiac examination, and normal ECG/telemetry,
      early TTE had a low yield for identifying high-risk cardiac causes. In EDOUs
      where TTE is not available daily, outpatient TTE for this patient subgroup may be
      considered to limit prolonged lengths of stay.

PMID- 28506592
TI  - Trends in Long-Term Mortality and Morbidity in Patients with No Early
      Complications after Stroke and Transient Ischemic Attack.
AB  - BACKGROUND: Advances in acute management and secondary prevention have reduced
      mortality and early recurrent risk after stroke and transient ischemic attack
      (TIA). However, whether improved outcomes are sustained long term among those
      without early adverse complications is not clear. We describe trends in long-term
      mortality and morbidity in patients with ischemic stroke or TIA who are
      clinically stable at 90 days. METHODS: This is a longitudinal cohort registry
      study (2003-2013) of patients presenting to stroke centers in Ontario, Canada,
      with a stroke or TIA, with no hospitalization, stroke, myocardial infarction
      (MI), institutionalization, or death within 90 days (N = 26,698). Primary
      outcomes were 1-, 3-, and 5-year age-adjusted composite rates of death, stroke or
      MI, and institutionalization, and secondary analyses evaluated outcomes
      individually. Trend tests were used to evaluate change over time. RESULTS: One
      year adjusted composite rates decreased from 9.3% in 2003 to 7.4% in 2012 (trend
      test P = .02). Significant decreases in 3-year (P < .001) and 5-year (P = .002)
      composite rates were also observed. Rates of recurrent stroke decreased at 1 and
      3 years (P < .01), but not 5 years (P = .21), whereas death rates declined across
      follow-up times. Conversely, rates of institutionalization increased at 3 and 5
      years (P < .01). CONCLUSIONS: Long-term mortality and morbidity post stroke and
      TIA have declined, confirming trends for improved long-term outcomes for patients
      clinically stable during the initial high-risk period. However, increased long
      term rates of institutionalization also suggest that stroke and TIA patients are
      at risk of long-term functional decline, despite improved clinical outcomes.
      Further studies evaluating challenges for sustaining functional gains after
      stroke and TIA are required.

PMID- 28506593
TI  - A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric
      Antigen Receptors by Affinity Optimization.
AB  - Chimeric antigen receptors (CARs) can effectively redirect cytotoxic T cells
      toward highly expressed surface antigens on tumor cells. The low expression of
      several tumor-associated antigens (TAAs) on normal tissues, however, hinders
      their safe targeting by CAR T cells due to on-target/off-tumor effects. Using the
      multiple myeloma (MM)-associated CD38 antigen as a model system, here, we present
      a rational approach for effective and tumor-selective targeting of such TAAs.
      Using "light-chain exchange" technology, we combined the heavy chains of two high
      affinity CD38 antibodies with 176 germline light chains and generated ~124 new
      antibodies with 10- to >1,000-fold lower affinities to CD38. After categorizing
      them into three distinct affinity classes, we incorporated the single-chain
      variable fragments of eight antibodies from each class into new CARs. T cells
      carrying these CD38-CARs were extensively evaluated for their on-tumor/off-tumor
      cytotoxicity as well as CD38-dependent proliferation and cytokine production. We
      identified CD38-CAR T cells of ~1,000- fold reduced affinity, which optimally
      proliferated, produced Th1-like cytokines, and effectively lysed CD382+ MM cells,
      but spared CD38+ healthy hematopoietic cells in vitro and in vivo. Thus, this
      systematic approach is highly suitable for the generation of optimal CARs for
      effective and selective targeting of TAAs.

PMID- 28506595
TI  - Plumbagin suppresses the migration and invasion of glioma cells via
      downregulation of MMP-2/9 expression and inaction of PI3K/Akt signaling pathway
      in vitro.
AB  - Plumbagin is a natural naphthoquinone constituent isolated from the roots of
      medicinal plant Plumbago zeylanica L., and has demonstrated anti-proliferative
      and anti-invasion activities in various cancer cells. However, its effect on the
      migration and invasion of glioma cells has not been elucidated. Therefore, human
      glioma U87 and U251 cells were treated with plumbagin at 1.0 and 2.0 MUM for 24
      h, and cell migration and invasion were assessed with scratch wound healing and
      invasion assays. The results showed that plumbagin significantly inhibited the
      migration and invasion of U87 and U251 cells, suppressed the activity and
      expression of MMP-2/-9, and inhibited the nuclear translocation of transcription
      factors Sp1 in the U87 and U251 cells. Moreover, plumbagin reduced the level of p
      PI3K and p-Akt in these cells. The combined treatment with plumbagin and PI3K/Akt
      agonist insulin-like growth factor-1 (IGF-1) reversed plumbagin-mediated
      inhibitory effects on MMP-2/-9 expression, cell migration and invasion. These
      findings suggest that the plumbagin-induced inhibition of glioma cell migration
      and invasion is closely associated with the downregulation of MMP-2/-9 expression
      and activity, and suppression of PI3K/Akt signaling pathway activation. Thus,
      plumbagin might be a potential anti-invasive agent in the treatment of glioma.

PMID- 28506594
TI  - Fingolimod and Teriflunomide Attenuate Neurodegeneration in Mouse Models of
      Neuronal Ceroid Lipofuscinosis.
AB  - CLN diseases are rare lysosomal storage diseases characterized by progressive
      axonal degeneration and neuron loss in the CNS, manifesting in disability,
      blindness, and premature death. We have previously demonstrated that, in animal
      models of infantile and juvenile forms of CLN disease (CLN1 and CLN3,
      respectively), secondary neuroinflammation in the CNS substantially amplifies
      neural damage, opening the possibility that immunomodulatory treatment might
      improve disease outcome. First, we recapitulated the inflammatory phenotype,
      originally seen in mice in autopsies of CLN patients. We then treated mouse
      models of CLN1 and CLN3 disease with the clinically approved immunomodulatory
      compounds fingolimod (0.5 mg/kg/day) and teriflunomide (10 mg/kg/day) by
      consistent supply in the drinking water for 5 months. The treatment was well
      tolerated and reduced T cell numbers and microgliosis in the CNS of both models.
      Moreover, axonal damage, neuron loss, retinal thinning, and brain atrophy were
      substantially attenuated in both models, along with reduced frequency of
      myoclonic jerks in Ppt1-/- mice. Based on these findings, and because side
      effects were not detected, we suggest that clinically approved immune modulators
      such as fingolimod and teriflunomide may be suitable to attenuate progression of
      CLN1 and CLN3 disease and, possibly, other orphan diseases with pathogenically
      relevant neuroinflammation.

PMID- 28506597
TI  - A practice pattern assessment of members of the Society of Pediatric Urology for
      evaluation and treatment of urinary tract dilation.
AB  - INTRODUCTION: Over the last decade the literature, including a multidisciplinary
      consensus statement, has supported a paradigm shift in management of urinary
      tract dilation, yet the impact on practice patterns has not been well documented.
      OBJECTIVE: This study aims to elucidate specific practice patterns for treatment
      of prenatal unilateral urinary tract dilation and to assess surgical intervention
      patterns for ureteropelvic junction obstruction. STUDY DESIGN: An online survey
      was distributed to 234 pediatric urologists through the Society of Pediatric
      Urology. The survey was composed of five clinical case scenarios addressing
      evaluation and management of unilateral urinary tract dilation. RESULTS: The
      response rate was 71% (n = 168). Circumcision status, gender, and grade were
      significant factors in recommending prophylactic antibiotics for newborn urinary
      tract dilation. Prophylactic antibiotic use in the uncircumcised male and female
      was twice that of a circumcised male for grade 3 (Table). This difference was
      minimized for grade 4. Use of VCUG was high for circumcised males with grade 3 or
      4 (Table). The choice of minimally invasive surgery for ureteropelvic junction
      repair increased with age from 19% for a 5-month-old, 49% for a 2-year-old, and
      85% for a 10-year-old. Notably, 44% of respondents would observe a 10-year-old
      with intermittent obstruction. Retrograde pyelography was recommended in
      conjunction with repair in 65% of respondents. Antegrade stent placement was the
      most common choice (38-47%) for urinary diversion after pyeloplasty. Regarding
      postoperative imaging, only 5% opted for routine renal scan whereas most would
      perform renal ultrasound alone. DISCUSSION: Practice patterns seen for use of
      prophylactic antibiotics are in agreement with the literature, which promotes
      selective use in those at highest risk for urinary tract infections.
      Interestingly, use of aggressive screening was not concordant with this
      literature. Several studies have indicated an increased usage of robotic
      pyeloplasty; however, results indicate that minimally invasive surgery is not
      preferred in those younger than 6 months. Study limitations include use of
      clinical case scenarios as opposed to actual clinical practice. CONCLUSION:
      Practice patterns for prophylactic antibiotic use for neonatal urinary tract
      dilation are dependent on gender, circumcision status, and grade. The use of
      minimally invasive surgery for ureteropelvic junction repair increased with
      patient age, with 50% preferring this modality at 2 years.

PMID- 28506598
TI  - Long-term dynamics in a soft-bottom amphipod community and the influence of the
      pelagic environment.
AB  - The processes and patterns seen in coastal benthic communities can be strongly
      influenced by the overlying pelagic environmental conditions. Integrating long
      term biological and environmental data (both benthic and pelagic) can give
      insight into the specific relationships between key benthic functional groups and
      natural temporal changes in the marine environment. The identity and abundance of
      amphipod species found at Station L4 (Western English Channel) were tracked for 7
      years (2008-2014), whilst simultaneously, annual changes in phytoplankton
      biomass, water temperature, salinity and chlorophyll a concentration were also
      characterized. The main species were persistent and showed little variability
      along the study period. Overall, however, there were significant changes in the
      structure of the whole community between sampling times, highlighting the
      importance of less numerically-dominant species in driving temporal variability.
      Surprisingly, the current study did not detect a significant influence of the
      phytoplankton biomass on benthic amphipod dynamics. On the other hand, there was
      a clear and constant correlation between bottom water temperatures and amphipod
      abundance. This pattern is different from that observed in other detritivorous
      species at L4, highlighting the complexity of benthic-pelagic coupling and the
      high variability of the response to pelagic conditions among different groups. As
      a result of the biogeographic position of the Western English Channel, the key
      role of amphipods in benthic communities, the influence of the temperature in
      their populations dynamics, as well as the solid baseline provided here and in
      previous studies, the monitoring of long-term amphipod dynamics in the English
      Channel could be a valuable tool to evaluate the biological effect of climate
      change over marine benthic communities.

PMID- 28506599
TI  - Application of vadose-zone monitoring system for real-time characterization of
      leachate percolation in and under a municipal landfill.
AB  - Leachates from solid-waste landfills are considered a severe threat to
      groundwater quality. The fate of pollutants in the waste and underlying
      unsaturated zone is crucial for evaluating environmental risks and selecting a
      restoration strategy. In this study, a vadose-zone monitoring system (VMS)
      installed in a municipal landfill was used, for the first time, to continuously
      track leachates percolation dynamics and assess their chemical transformation
      across the entire thickness of the waste body (15m) and underlying unsaturated
      zone (16m) to the water table. Winter rains were found to quickly infiltrate
      through the waste and underlying vadose zone despite a clay cover that was
      implemented as part of a restoration and leachate-prevention strategy. Within the
      waste body, the flow pattern was controlled by preferential flow paths, which
      changed frequently. It is hypothesized that ongoing decomposition of the waste
      creates dynamic variations in the waste's physical structure and flow pattern.
      Water samples collected from the waste layer indicated the formation of highly
      polluted leachates. The chemical composition in the waste body showed extreme
      variability between sampling points with respect to DOC (407-31,464mg/L), BOD/COD
      ratios (0.07-0.55), Fe2+ (6.8-1154mg/L), ammonium (68-2924mg/L) and heavy metal
      concentrations. Environmental hot spots creating concentrated, aggressive, "acid
      phase" leachates still exist in the waste more than 13years after closing the
      landfill. However, continuous changes in the flow pattern and moisture
      distribution affected the creation and decay of such environments. In the
      underlying sandy vadose zone, some sections repeatedly exhibited stronger and
      faster flow characteristics than others. These local fluxes of concentrated
      leachates rapidly transported heavy contaminant loads toward the groundwater.
      However results showed evidence of continual attenuation processes in the deep
      vadose zone, with the anaerobic digestion of organic matter, as well as the
      significant retention of heavy metals.

PMID- 28506601
TI  - A flatline Lead I in a neonate with suspected congenital heart disease.
AB  - In a neonate with bradycardia and hypoxia, and clinical concern for critical
      congenital heart disease (CCHD), highly unusual ECG findings were present. These
      included a flatline Lead 1, and identical Leads 2, 3, and AVF. These
      abnormalities were due to bilateral arm to leg lead exchanges and not to heart
      disease. Complete cardiac workup including echocardiogram was normal.

PMID- 28506600
TI  - Cardiac hemangioma caused ventricular arrhythmia: A rare case and literature
      review.
AB  - Cardiac hemangioma is a rare primary cardiac tumor. We reported the case of
      patient with left ventricular hemangioma who was referred to our hospital
      complaining of palpitation for one week. 24 h Holter revealed high episode of
      ventricular arrhythmia. Echocardiography showed a mass at left ventricle, which
      was also confirmed by MRI. The mass was successfully resected and postoperative
      pathology confirmed cardiac capillary hemangioma. The patient recovered well with
      no cardiac arrhythmia after surgery over 12 months of follow-up.

PMID- 28506596
TI  - Advances in medical imaging for the diagnosis and management of common
      genitourinary cancers.
AB  - Medical imaging of the 3 most common genitourinary (GU) cancers-prostate
      adenocarcinoma, renal cell carcinoma, and urothelial carcinoma of the bladder-has
      evolved significantly during the last decades. The most commonly used imaging
      modalities for the diagnosis, staging, and follow-up of GU cancers are computed
      tomography, magnetic resonance imaging (MRI), and positron emission tomography
      (PET). Multiplanar multidetector computed tomography and multiparametric MRI with
      diffusion-weighted imaging are the main imaging modalities for renal cell
      carcinoma and urothelial carcinoma, and although multiparametric MRI is rapidly
      becoming the main imaging tool in the evaluation of prostate adenocarcinoma,
      biopsy is still required for diagnosis. Functional and molecular imaging using 18
      fluorodeoxyglucose-PET and sodium fluoride-PET are essential for the diagnosis,
      and especially follow-up, of metastatic GU tumors. This review provides an
      overview of the latest advances in the imaging of these 3 major GU cancers.

PMID- 28506602
TI  - Ventricular tachycardia score - A novel method for wide QRS complex tachycardia
      differentiation - Explained.
AB  - Philosophy, merits and limitations of a novel method for wide QRS complex
      tachycardia differentiation, based on a scoring system and called the ventricular
      tachycardia (VT) score, were explained. The following criteria were assigned one
      point: initial dominant R wave in V1; initial r>40 ms in V1 or V2; notched S in
      V1; initial R wave in aVR; lead II RWPT>=50 ms; and absence of an RS in leads V1
      V6. Atrioventricular dissociation (including fusion/capture beats and partial
      dissociation) was assigned two points. We recommend >=3 VT score points for a
      firm diagnosis of VT. A cut-off >=1 point can be used for diagnosis of VT when
      highest overall accuracy rather than error-free diagnosis is desired. However, in
      case of VT score of 0-2 (i.e., not fully diagnostic ECG), we recommend using
      other options (electrophysiological study, clinical data, previous and following
      ECGs, etc.) for confirming the diagnosis.

PMID- 28506603
TI  - Exudative retinal detachment.
AB  - Exudative retinal detachment develops when fluid collects in the subretinal
      space. The subretinal space between the photoreceptors and the retinal pigment
      epithelium is the remnant of the embryonic optic vesicle. In the developed eye
      the subretinal space is of minimal size, but it can reopen under pathological
      conditions that disrupt the integrity of blood-retinal barrier. Inflammatory,
      infectious, infiltrative, neoplastic, vascular, and degenerative conditions may
      be associated with blood-retinal barrier breakdown and the sequential development
      of exudative retinal detachment. We elaborate on the pathogenesis and the
      differential diagnosis of exudative retinal detachment and specifically discuss
      the spectrum of diseases associated with exudative retinal detachment in uveitis
      clinics.

PMID- 28506604
TI  - The supraciliary space as a suitable pathway for glaucoma surgery: Ho-hum or home
      run?
AB  - The supraciliary space is a physiological route for aqueous humor outflow located
      anteriorly between the outer surface of the ciliary body and the internal surface
      of the sclera. Posteriorly, the suprachoroidal space is located between the
      choroid and the internal surface of the sclera. These spaces have been targeted
      as suitable and helpful pathways for glaucoma treatment, alternatives to the
      traditional subconjunctival space. The subconjunctival surgical pathway is
      affected by several limitations such as poor cosmesis, a lifetime risk for
      endophthalmitis, and an unpredictable wound healing response. Because of these
      limitations, the supraciliary space has gained growing interest as a possible
      target for new glaucoma drainage devices such as: Gold Micro Shunt (SOLX Inc.;
      Waltham, MA, USA), iStent Supra (Glaukos Corporation, Laguna Hills, CA, USA),
      CyPass Micro-Stent (Transcend Medical Inc., Menlo Park, CA, USA), Aquashunt (OPKO
      health Inc., Miami, FL, USA), STARflo (iSTAR Medical, Isnes, Belgium), and
      Esnoper-Clip implant (AJL Ophthalmics, Alava, Spain). We review the current
      literature concerning the supraciliary space to evaluate its safety and efficacy
      as a suitable pathway for glaucoma surgical treatment.

PMID- 28506606
TI  - Metabolic syndrome and in-hospital outcomes among pancreatic cancer patients.
AB  - AIMS: Metabolic Syndrome (MetS) is an important etiologic and prognostic factor
      for pancreatic cancer, but few studies have assessed health outcomes among
      hospitalized pancreatic cancer patients. We examined the associations between
      MetS and in-hospital outcomes, i.e. pancreatic resection, post-surgery
      complications, in-hospital mortality and discharge disposition among hospitalized
      patients with pancreatic cancer. METHODS: Using the Healthcare Cost and
      Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) dataset from 2007 to
      2011, we obtained data on 47,386 patients hospitalized with a primary diagnosis
      of pancreatic cancer. Descriptive statistics and multivariable regression models
      were used to compute estimates, odds ratios and 95% confidence intervals
      adjusting for age, race/ethnicity, and socioeconomic status. RESULTS: Pancreatic
      cancer patients with MetS were more likely to undergo pancreatic resection (OR:
      1.14, 95% CI: 1.04-1.25) compared to those without MetS. However they were less
      likely to experience post-surgical complications (OR: 0.90, 95% CI: 0.81-0.99),
      discharge to a skilled nursing facility (OR: 0.90, 95% CI: 0.83-0.93), and less
      likely to experience in-hospital mortality (OR: 0.52, 95% CI: 0.44-0.61) compared
      to those without MetS. CONCLUSION: Hospitalized pancreatic cancer patients with a
      clinical diagnosis of MetS were more likely to receive pancreatic resection, and
      had reduced odds of post-surgical complications and in-hospital mortality. If
      confirmed in future studies, then better understanding of the biological
      mechanisms underlying this association will be needed, potentially leading to the
      development of clinical and/or molecular biomarkers to improve early diagnosis of
      pancreatic cancer and identify patients that may benefit from pancreatic
      resection.

PMID- 28506607
TI  - Corrigendum to "The role of Ntcp, Oatp2, Bsep and Mrp2 in liver injury induced by
      Dioscorea bulbifera L. and Diosbulbin B in mice" [Environ. Toxicol. Pharmacol. 51
      (2017) 16-22].

PMID- 28506605
TI  - Post-Traumatic Stress Disorder among Older Adults Experiencing Motor Vehicle
      Collision: A Multicenter Prospective Cohort Study.
AB  - OBJECTIVE: To characterize risk factors for and consequences of post-traumatic
      stress disorder (PTSD) among older adults evaluated in the emergency department
      (ED) following motor vehicle collision (MVC). DESIGN: Prospective multicenter
      longitudinal study (2011-2015). SETTING: 9 EDs across the United States.
      PARTICIPANTS: Adults aged 65 years and older who presented to an ED after MVC
      without severe injuries. MEASUREMENTS: PTSD symptoms were assessed 6 months after
      the ED visit using the Impact of Event Scale-Revised. RESULTS: Of 223 patients,
      clinically significant PTSD symptoms at 6 months were observed in 21% (95% CI 16%
      26%). PTSD symptoms were more common in patients who did not have a college
      degree, had depressive symptoms prior to the MVC, perceived the MVC as life
      threatening, had severe ED pain, and expected their physical or emotional
      recovery time to be greater than 30 days. Three factors (ED pain severity [0-10
      scale], perceived life-threatening MVC [0-10 scale], and pre-MVC depressive
      symptoms [yes to either of two questions]), predicted 6-month PTSD symptoms with
      an area under the curve of 0.76. Compared to patients without PTSD symptoms,
      those with PTSD symptoms were at higher risk for persistent pain (72% versus
      30%), functional decline (67% versus 42%), and new disability (49% versus 18%).
      CONCLUSIONS: Among older adults treated in the ED following MVC, clinically
      significant PTSD symptoms at 6 months were present in 21% of patients and were
      associated with adverse health outcomes. Increased risk for PTSD development can
      be identified with moderate accuracy using information readily available in the
      ED.

PMID- 28506608
TI  - PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive
      interface.
AB  - OBJECTIVE: To characterize and deliver fabricated CHX-loaded PLGA-nanoparticles
      inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin
      dentin interface. METHODS: Nanoparticles fabricated by emulsion evaporation were
      assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles
      to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo
      CHX-release profiles using extracted teeth connected to experimental setup
      simulating pulpal hydrostatic pressure were investigated. Furthermore,
      nanoparticles association/interaction with a commercial dentin-adhesive applied
      to demineralized dentin substrates were examined. RESULTS: The results showed
      that the formulated nanoparticles demonstrated attractive physicochemical
      properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation
      and gradual CHX release profiles. Nanoparticles delivered efficiently inside
      dentinal-tubules structure to sufficient depth (>10MUm) against the simulated
      upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and
      were attached/retained on collagen-fibrils. These results verified the potential
      significance of this newly introduced drug-delivery therapeutic strategy for
      future clinical applications and promote for a new era of future dental research.
      SIGNIFICANCE: This innovative drug-delivery strategy has proven to be a reliable
      method for delivering treatments that could be elaborated for other clinical
      applications in adhesive and restorative dentistry.

PMID- 28506609
TI  - Ageing kinetics and strength of airborne-particle abraded 3Y-TZP ceramics.
AB  - OBJECTIVE: The combined effects of alumina airborne-particle abrasion and
      prolonged in vitro ageing on the flexural strength of 3Y-TZP ceramic have been
      studied. The aim was to identify the different effects on the surface and
      subsurface regions that govern the performance of this popular bioceramic known
      for its susceptibility to low-temperature degradation (LTD). METHODS: As-sintered
      or airborne-particle abraded 3Y-TZP discs were subjected to ageing at 134 degrees
      C for up to 480h. Biaxial flexural strength was measured and the relative amount
      of monoclinic phase determined using X-ray diffraction. The transformed zone
      depth (TZD) was observed on cross-sections with scanning electron microscopy
      coupled with a focused ion beam. Segmented linear regression was used to analyze
      the flexural strength and TZD as functions of the ageing time. RESULTS: A two
      step linear ageing kinetics was detected in airborne-particle abraded specimens,
      reflecting the different microstructures through which the LTD proceeds into the
      bulk. A 10MUm thick altered zone under the abraded surface was involved in both
      the surface strengthening and the increased ageing resistance. When the zone was
      annihilated by the LTD, the strength of the ceramic specimens and the speed of
      LTD returned to the values measured before abrasion. Even at prolonged ageing
      times, the strength of abraded groups was not lower than that of as-sintered
      groups. SIGNIFICANCE: Both the ageing kinetics and the flexural strength were
      prominently affected by airborne-particle abrasion, which altered the subsurface
      microstructure and phase composition. Airborne-particle abrasion was not harmful
      to the 3Y-TZP ceramics' stability.

PMID- 28506610
TI  - Decreased Serum Sirtuin-1 in COPD.
AB  - BACKGROUND: The protein deacetylase sirtuin-1 (SIRT1) is an antiaging molecule
      that is decreased in the lung in patients with COPD. Recently, SIRT1 was reported
      to be detectable in serum, but serum SIRT1 (s120S) levels have not yet been
      reported in patients with COPD. METHODS: Serum SIRT1 protein of all samples was
      measured by Western blot, and the SIRT1 protein band densities were calculated
      and compared with clinical parameters. RESULTS: Several molecular sizes of SIRT1,
      including 120 kDa (actual size) and fragments (102 and 75 kDa) were quantified by
      Western blot. Among them, only the 120-kDa s120S was significantly decreased in
      patients with COPD compared with the control subjects without COPD (s120S ratio
      in healthy subjects = 0.90 +/- 0.34 vs those with COPD = 0.68 +/- 0.24; P = .014)
      and was positively correlated with airway obstruction (FEV1/FVC, r = 0.31; P =
      .020); its severity measured by FEV1 % predicted (r = 0.29; P = .029). s120S also
      showed a positive correlation with BMI (r = 0.36; P = .0077) and diffusing
      capacity of the lung per unit volume (the carbon monoxide transfer coefficient:
      KCO%) (r = 0.32; P = .025). It was also significantly decreased with increasing
      severity of lung emphysema (r = -0.40; P = .027) and with a clinical history of
      frequent COPD exacerbations (infrequent vs frequent, 0.76 +/- 0.20 vs 0.56 +/-
      0.26; P = .027). SIRT1 was not detected in supernatant of A549 and primary
      epithelial cells in normal culture conditions. CONCLUSIONS: s120S was decreased
      in the patients with COPD, potentially as reflected by the reduced SIRT1 within
      cells as a result of oxidative stress, and might be a potential biomarker for
      certain disease characteristics of COPD.

PMID- 28506612
TI  - Identification of Pulmonary Hypertension Caused by Left-Sided Heart Disease
      (World Health Organization Group 2) Based on Cardiac Chamber Volumes Derived From
      Chest CT Imaging.
AB  - BACKGROUND: Evaluations of patients with pulmonary hypertension (PH) commonly
      include chest CT imaging. We hypothesized that cardiac chamber volumes calculated
      from the same CT scans can yield additional information to distinguish PH related
      to left-sided heart disease (World Health Organization group 2) from other PH
      subtypes. METHODS: Patients who had PH confirmed by right heart catheterization
      and contrast-enhanced chest CT studies were enrolled in this retrospective
      multicenter study. Cardiac chamber volumes were calculated using automated
      segmentation software and compared between group 2 and non-group 2 patients with
      PH. RESULTS: This study included 114 patients with PH, 27 (24%) of whom were
      classified as group 2 based on their pulmonary capillary wedge pressure. Patients
      with group 2 PH exhibited significantly larger median left atrial (LA) volumes
      (118 mL vs 63 mL; P < .001), larger median left ventricular (LV) volumes (90 mL
      vs 76 mL; P = .02), and smaller median right ventricular (RV) volumes (173 mL vs
      210 mL; P = .005) than did non-group 2 patients. On multivariate analysis
      adjusted for age, sex, and mean pulmonary arterial pressure, group 2 PH was
      significantly associated with larger median LA and LV volumes (P < .001 and P =
      .008, respectively) and decreased volume ratios of RA/LA, RV/LV, and RV/LA (P =
      .001, P = .004, and P < .001, respectively). Enlarged LA volumes demonstrated a
      high discriminatory ability for group 2 PH (area under the curve, 0.92; 95% CI,
      0.870-0.968). CONCLUSIONS: Volumetric analysis of the cardiac chambers from
      nongated chest CT scans, particularly with findings of an enlarged left atrium,
      exhibited high discriminatory ability for identifying patients with PH due to
      left-sided heart disease.

PMID- 28506613
TI  - Effect of high pressure on the saccharification of starch in the tuberous root of
      sweet potato (Ipomoea batatas).
AB  - We analyzed the effect of high hydrostatic pressure (HHP) treatment on reducing
      sugar production in the tuberous root of sweet potato (Ipomoea batatas), based on
      pressure-gelatinization of starch and subsequent saccharification by internal
      amylases. HHP treatment at up to 600MPa at ambient temperature for 10min did not
      apparently affect the reducing sugar concentration in tuberous root. However, HHP
      treatment at 100 to 500MPa and 60 degrees C or 70 degrees C for 10min increased
      reducing sugar concentration as both the pressure and temperature increased. The
      reducing sugar concentration after HHP treatment at 500MPa and 70 degrees C for
      10min was roughly comparable to that of the thermal treatment control (80 degrees
      C for 10min under atmospheric pressure). HHP treatment enabled the gelatinization
      and enzymatic saccharification of starch in the tuberous root of sweet potato, at
      a lower temperature than required by thermal treatment at atmospheric pressure.

PMID- 28506614
TI  - Retrospective analysis of skin complications related to bone-anchored hearing aid
      implant: association with surgical technique, quality of life, and audiological
      benefit.
AB  - INTRODUCTION: The bone-anchored hearing aid is an effective form of auditory
      rehabilitation. Due to the nature of the implant, the most common complications
      are skin related. A number of alternative surgical implantation techniques have
      been used to reduce the frequency and severity of skin complications, including
      the U-shaped graft and the linear incision. OBJECTIVE: To assess skin
      complications and their association with surgical technique, quality of life, and
      audiological benefit in patients with bone-anchored hearing aids. METHODS: This
      was a retrospective study conducted in a tertiary referral center in Bogota,
      Colombia. Patients who had been fitted with a bone-anchored hearing aid implant
      (unilaterally or bilaterally) for at least 6 months were included in the study.
      The Holgers classification was used to classify skin complications (Grade 0=none;
      Grade 1=erythema; Grade 2=erythema and discharge; Grade 3=granulation tissue; and
      Grade 4=inflammation/infection resulting in the removal of the abutment). The
      Glasgow Benefit Inventory questionnaire was used to determine quality of life,
      and the Abbreviated Profile of Hearing Aid Benefit questionnaire was used to
      determine the subjective audiological benefit. RESULTS: A total of 37 patients
      were included in the study (30 with unilateral implants and 7 with bilateral
      implant). Of the 44 implants evaluated, 31 (70.3%) were associated with skin
      complications (7 [15.9%] Grade 1; 4 [9.1%] Grade 2; 15 [34.1%] Grade 3, 5 [11.4%]
      Grade 4). The U-shaped graft was statistically associated with major
      complications (Grades 3 and 4) compared with the linear incision technique
      (p=0.045). No statistically significant differences were found between
      Abbreviated Profile of Hearing Aid Benefit scores and severity of complications.
      Similarly, no differences were found between Glasgow Benefit Inventory physical
      health questions and skin complications. CONCLUSION: Despite the high frequency,
      skin complications did not seem to affect quality of life or subjective
      audiological benefits of patients with bone-anchored hearing aids.

PMID- 28506611
TI  - Clinical and Genetic Associations of Objectively Identified Interstitial Changes
      in Smokers.
AB  - BACKGROUND: Smoking-related lung injury may manifest on CT scans as both
      emphysema and interstitial changes. We have developed an automated method to
      quantify interstitial changes and hypothesized that this measurement would be
      associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B)
      polymorphism. METHODS: Using CT scans from the Genetic Epidemiology of COPD
      Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated
      the percentage of the lung occupied by interstitial subtypes. RESULTS: A total of
      8,345 participants had clinical and CT scanning data available. A 5% absolute
      increase in interstitial changes was associated with an absolute decrease in FVC
      % predicted of 2.47% (P < .001) and a 1.36-point higher St. George's Respiratory
      Questionnaire score (P < .001). Among the 6,827 participants with mortality data,
      a 5% increase in interstitial changes was associated with a 29% increased risk of
      death (P < .001). These associations were present in a subgroup without visually
      defined interstitial lung abnormalities, as well as in those with normal
      spirometric test results, and in those without chronic respiratory symptoms. In
      non-Hispanic whites, for each copy of the minor allele of the MUC5B promoter
      polymorphism, there was a 0.64% (P < .001) absolute increase in the percentage of
      lung with interstitial changes. CONCLUSIONS: Objective interstitial changes on CT
      scans were associated with impaired lung function, worse quality of life,
      increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting
      that these changes may be a marker of susceptibility to smoking-related lung
      injury, detectable even in those who are healthy by other measures.

PMID- 28506615
TI  - Modelling asymmetric somitogenesis: Deciphering the mechanisms behind species
      differences.
AB  - Somitogenesis is one of the major hallmarks of bilateral symmetry in vertebrates.
      This symmetry is lost when retinoic acid (RA) signalling is inhibited, allowing
      the left-right determination pathway to influence somitogenesis. In all three
      studied vertebrate model species, zebrafish, chicken and mouse, the frequency of
      somite formation becomes asymmetric, with slower gene expression oscillations
      driving somitogenesis on the right side. Still, intriguingly, the resulting left
      right asymmetric phenotypes differ significantly between these model species.
      While somitogenesis is generally considered as functionally equivalent among
      different vertebrates, substantial differences exist in the subset of oscillating
      genes between different vertebrate species. Variation also appears to exist in
      the way oscillations cease and somite boundaries become patterned. In addition,
      in absence of RA, the FGF8 gradient thought to constitute the determination
      wavefront becomes asymmetric in zebrafish and mouse, extending more anteriorly to
      the right, while remaining symmetric in chicken. Here we use a computational
      modelling approach to decipher the causes underlying species differences in
      asymmetric somitogenesis. Specifically, we investigate to what extent differences
      can be explained from observed differences in FGF asymmetry and whether
      differences in somite determination dynamics may also be involved. We demonstrate
      that a simple clock-and-wavefront model incorporating the observed left-right
      differences in somitogenesis frequency readily reproduces asymmetric
      somitogenesis in chicken. However, incorporating asymmetry in FGF signalling was
      insufficient to robustly reproduce mouse or zebrafish asymmetry phenotypes. In
      order to explain these phenoptypes we needed to extend the basic model,
      incorporating species-specific details of the somitogenesis determination
      mechanism. Our results thus demonstrate that a combination of differences in FGF
      dynamics and somite determination cause species differences in asymmetric
      somitogenesis. In addition,they highlight the power of using computational models
      as well as studying left-right asymmetry to obtain more insight in somitogenesis.

PMID- 28506616
TI  - Outcomes of Hip Arthroscopy in Competitive Athletes.
AB  - PURPOSE: To evaluate the minimum 2-year postoperative clinical outcomes and the
      rate of return to sports in athletes who underwent capsular plication for the
      treatment of ligamentous laxity and/or borderline dysplasia during hip
      arthroscopy for the treatment of femoroacetabular impingement and labral
      pathology. METHODS: Since 2008, data were prospectively collected on patients who
      underwent hip arthroscopy for the treatment of femoroacetabular impingement
      and/or labral tears. Inclusion criteria were as follows: athlete at the high
      school, collegiate, or professional levels preoperatively, underwent capsular
      plication, and preoperatively recorded patient-reported outcome scores including
      modified Harris hip score (mHHS), nonarthritic athletic hip score (NAHS), hip
      outcome score-sports-specific subscale (HOS-SSS), and visual analog scale (VAS).
      Exclusion criteria were as follows: <16 years old, preoperative Tonnis grade >1,
      and previous hip conditions. Sports activity and competitive levels were
      collected at a minimum of 2 years postoperatively. RESULTS: Fifty-one hips (49
      patients) met the inclusion criteria, and 41 hips (39 patients) had minimum 2
      year follow-up (80.4% follow-up). Mean mHHS increased from 67.1 preoperatively to
      83.5 (P < .0001). Mean NAHS increased from 66.8 to 88.8 (P < .0001). Mean HOS-SSS
      improved from 46.8 to 80.1 (P < .0001). Mean VAS decreased from 5.1 to 1.7 (P <
      .0001). Thirty-five (85.4%) hip arthroscopies allowed the patients to return to
      sports at follow-up. Thirty-four (82.9%) hip arthroscopies allowed the patients
      to maintain their competitive physical abilities at follow-up. CONCLUSIONS:
      Patient-reported outcomes and VAS in athletes significantly improved at a minimum
      of 2 years after capsular plication as a part of hip arthroscopy addressing
      varying pathologies. In addition, most patients returned to sports at similar or
      higher competitive levels. These results suggest that capsular plication is a
      favorable treatment option in athletes with ligamentous laxity and/or borderline
      dysplasia. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 28506617
TI  - Arthroscopic Treatment of Hip Pain in Adolescent Patients With Borderline
      Dysplasia of the Hip: Minimum 2-Year Follow-Up.
AB  - PURPOSE: To examine arthroscopic treatment of hip pain in patients with
      borderline hip dysplasia (lateral center edge angle [LCEA] between 20 degrees 
      and 25 degrees ). METHODS: From 2008 to 2013, patients below 18 years of age who
      underwent arthroscopic hip surgery with an LCEA between 20 degrees  and 25
      degrees  were retrospectively matched 1:1 to a control group without dysplasia
      (LCEA >=25 degrees ) based on age, gender, femoroplasty, labral treatment, and
      capsular plication. Indications for surgery included failure to improve with
      nonoperative treatments and anti-inflammatory medications after 3 months. Patient
      reported outcome data were collected using modified Harris hip score, hip outcome
      score-activities of daily living subscale, hip outcome score-sports-specific
      subscale, nonarthritic athletic hip score, and visual analog scale. RESULTS: From
      2008 to 2013, 168 patients below the age of 18 underwent arthroscopic hip
      surgery. Twenty-one patients met inclusion criteria and were matched 1:1 to a
      control group. Follow-up was achieved for 17 patients in both groups (81%). Mean
      follow-up time, age, and LCEA were 2.19 years, 15.5 years, and 22.3 degrees  for
      the dysplastic group and 2.16 years, 16.0 years, and 31.2 degrees  for the
      control group, respectively. Preoperative patient-reported outcomes between
      groups were not statistically different. At the latest follow-up, both groups
      showed statistically significant improvement over baseline in modified Harris hip
      score, hip outcome score-activities of daily living subscale, hip outcome score
      sports-specific subscale, nonarthritic athletic hip score, and visual analog
      scale (P < .001). Latest follow-up scores were not statistically different
      between groups. CONCLUSIONS: This study shows favorable 2-year outcomes in
      adolescent patients with borderline dysplasia undergoing labral treatment and
      capsular plication. Outcomes in the borderline dysplastic patients were as good
      as those of a control group. Although adolescents with borderline dysplasia have
      traditionally been a challenging group of patients to treat, these results
      suggest that an arthroscopic approach that addresses both labral pathology and
      instability may be beneficial. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 28506618
TI  - The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and
      aberrant activity amongst VTA dopamine neurons in both familiar and novel space.
AB  - Recurrent seizures that define epilepsy are often accompanied by psychosocial
      problems and cognitive deficits with incompletely understood aetiology. We
      therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to
      examine potential seizure-associated neuropathologies, focusing on motivation,
      memory and novel-environment-induced activation of midbrain dopaminergic neurons.
      In addition to recurrent seizures, we found that PTZ kindling led to a strong
      suppression of novelty-driven exploration while largely sparing fear-driven
      exploration. The deficits in exploratory drive may be relevant for other
      cognitive impairments since reduced unassisted rearing in a learning arena
      correlated with poorer spatial memory of object location. Using c-Fos
      immunofluorescence as a marker of neuronal activity, we observed that dopamine
      neurons within the ventral tegmental area (VTA) of PTZ kindled mice demonstrate
      hyperactivity at baseline and hypoactivity in response to a novel environment
      compared to saline-injected cagemate controls. These data extend previous
      findings of PTZ kindling-mediated disruptions of hippocampal processes important
      for novel environment recognition and learning by demonstrating PTZ kindling also
      induces motivational deficits that are associated with reduced stimulus-evoked
      activation of VTA dopamine neurons. More broadly, these data help understand the
      aetiology of complex behavioural changes in the PTZ kindling model, and may
      assist in the development of superior diagnoses and treatments for epilepsy.

PMID- 28506619
TI  - Long-term reliability of the visual EEG Poffenberger paradigm.
AB  - The Poffenberger paradigm is a simple perception task that is used to estimate
      the speed of information transfer between the two hemispheres, the so-called
      interhemispheric transfer time (IHTT). Although the original paradigm is a
      behavioral task, it can be combined with electroencephalography (EEG) to assess
      the underlying neurophysiological processes during task execution. While older
      studies have supported the validity of both paradigms for investigating
      interhemispheric interactions, their long-term reliability has not been assessed
      systematically before. The present study aims to fill this gap by determining
      both internal consistency and long-term test-retest reliability of IHTTs produced
      by using the two different versions of the Poffenberger paradigm in a sample of
      26 healthy subjects. The results show high reliability for the EEG Poffenberger
      paradigm. In contrast, reliability measures for the behavioral Poffenberger
      paradigm were low. Hence, our results indicate that electrophysiological measures
      of interhemispheric transfer are more reliable than behavioral measures; the
      later should be used with caution in research investigating inter-individual
      differences of neurocognitive measures.

PMID- 28506620
TI  - Bombesin administration impairs memory and does not reverse memory deficit caused
      by sleep deprivation.
AB  - Sleep deprivation impairs performance in emotional memory tasks, however this
      effect on memory is not completely understood. Possible mechanisms may involve an
      alteration in neurotransmission systems, as shown by the fact that many drugs
      that modulate neural pathways can prevent memory impairment by sleep loss.
      Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory
      molecule of emotional memory through the modulation of other neurotransmission
      systems. Thus, the present study addressed the effect of intraperitoneal (IP)
      administration of bombesin (BB) (2.5, 5.0 and 10.0MUg/kg), a GRP agonist, on the
      performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task,
      after sleep deprivation, using the modified multiple platforms method (MMPM).
      Sleep deprived animals exhibited acquisition and retention impairment that was
      not prevented by BB injection. In addition, non-sleep deprived animals treated
      with BB before and after the training session, but not before the test, have
      shown a retention deficit. In summary, BB did not improve the memory impairment
      by sleep loss and, under normal conditions, produced a memory consolidation
      deficit.

PMID- 28506621
TI  - ZENK expression following conspecific and heterospecific playback in the zebra
      finch auditory forebrain.
AB  - Zebra finches (Taeniopygia guttata) are sexually dimorphic songbirds, not only in
      appearance but also in vocal production: while males produce both calls and
      songs, females only produce calls. This dimorphism provides a means to contrast
      the auditory perception of vocalizations produced by songbird species of varying
      degrees of relatedness in a dimorphic species to that of a monomorphic species,
      species in which both males and females produce calls and songs (e.g., black
      capped chickadees, Poecile atricapillus). In the current study, we examined
      neuronal expression after playback of acoustically similar hetero- and
      conspecific calls produced by species of differing phylogenetic relatedness to
      our subject species, zebra finch. We measured the immediate early gene (IEG) ZENK
      in two auditory areas of the forebrain (caudomedial mesopallium, CMM, and
      caudomedial nidopallium, NCM). We found no significant differences in ZENK
      expression in either male or female zebra finches regardless of playback
      condition. We also discuss comparisons between our results and the results of a
      previous study conducted by Avey et al. [1] on black-capped chickadees that used
      similar stimulus types. These results are consistent with the previous study
      which also found no significant differences in expression following playback of
      calls produced by various heterospecific species and conspecifics [1]. Our
      results suggest that, similar to black-capped chickadees, IEG expression in zebra
      finch CMM and NCM is tied to the acoustic similarity of vocalizations and not the
      phylogenetic relatedness of the species producing the vocalizations.

PMID- 28506622
TI  - Meta-analyses of RELN variants in neuropsychiatric disorders.
AB  - Reelin is a critical extracellular matrix glycoprotein and implicated in
      neurodevelopment and psychiatric disorders in animal model studies. The genetic
      polymorphism of RELN has also been reported to be associated with several
      psychiatric disorders, but the results remain controversial. Here, we conducted
      meta-analyses of RELN gene SNPs and related neuropsychiatric disorders
      (schizophrenia, autistic spectrum disorders, attention-deficit hyperactivity
      disorder, Alzheimer's disease and bipolar disorders). A total of 12 SNPs
      (rs736707, rs362691, rs607755, rs2229864, rs7341475, rs262355, rs362719,
      rs11496125, g.-888G>C, rs2299356, rs528528, and rs4298437) in RELN gene were
      included into meta-analyses. Subgroup analyses based on ethnicity were performed.
      We found that RELN rs736707 was significantly related with psychiatric disorders
      (schizophrenia, autism spectrum disorders and attention-deficit hyperactivity
      disorder) in Asian group (C vs T, OR=1.26, 95% CI=1.13-1.41, P<0.01, FDR<0.01),
      and rs7341475 was only significantly associated with reduced risk of
      schizophrenia in Caucasian (A vs G, OR=0.88, 95% CI=0.82-0.95, P<0.01, FDR<0.01).
      No association of other SNPs and psychiatric disorders is found. These findings
      suggest a role of RELN SNPs in psychiatric diseases, and indicate that further
      researches in populations with different genetic background and studies with
      larger sample size are of great value.

PMID- 28506623
TI  - MeCP2-deficient mice have reduced alpha4 and alpha6 nicotinic receptor mRNA and
      altered behavioral response to nicotinic agonists.

PMID- 28506624
TI  - Emerging Pathogenic Respiratory Mycoplasma hominis Infections in Lung Transplant
      Patients: Time to Reassesses it's Role as a Pathogen?

PMID- 28506625
TI  - Differences between GesEPOC and GOLD in 2017.

PMID- 28506626
TI  - Major Changes in the Spanish COPD Guidelines (GesEPOC) 2017: Crossing Bridges.

PMID- 28506628
TI  - Corrections.

PMID- 28506629
TI  - Hippocampal information processing across sleep/wake cycles.
AB  - According to a two-stage memory consolidation model, during waking theta states,
      afferent activity from the neocortex to the hippocampus induces transient
      synaptic modification in the hippocampus, where the information is deposited as a
      labile form of memory trace. During subsequent sharp-wave ripples (SPW-Rs), the
      newly acquired hippocampal information is transferred to the neocortex and stored
      as a long-lasting memory trace. Consistent with this hypothesis, waking theta
      states and SPW-Rs distinctly control information flow in the hippocampal
      entorhinal loop. Although both waking theta states and rapid eye movement (REM)
      sleep are characterized by prominent hippocampal theta oscillations, the two
      brain states involve distinct temporal coordination and oscillatory coupling in
      the hippocampal-entorhinal circuit. While distinct brain states have distinct
      network dynamics, firing rates of individual neurons in the hippocampal
      entorhinal circuitry follow lognormal-like distributions in all states. Firing
      rates of the same neurons are positively correlated across brain states and
      testing environments, suggesting that memory is allocated in preconfigured,
      rather than tabula rasa-type, skewed neuronal networks. The fast-firing minority
      and slow-firing majority neurons, which can support network stability and
      flexibility, are under distinct homeostatic regulations that are initiated by
      spindles and SPW-Rs during slow wave sleep and implemented during subsequent REM
      sleep.

PMID- 28506627
TI  - RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I
      Antibody-Positive Systemic Sclerosis.
AB  - Systemic sclerosis is a systemic autoimmune and connective tissue disorder
      associated with the human leukocyte antigen locus. However, the functional
      relationship between human leukocyte antigen gene(s) and disease development
      remains unknown. To elucidate major histocompatibility complex-linked systemic
      sclerosis genetics, we performed genotyping of major histocompatibility complex
      borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti
      topoisomerase I antibody-positive patients and 561 healthy controls, all of
      Japanese descent. Those results revealed two major histocompatibility complex
      haplotypes associated with systemic sclerosis. Exome sequencing and targeted
      analysis of these risk haplotypes identified rs17847931 in RXRB as a
      susceptibility variant (P = 1.3 * 10-15; odds ratio [OR] = 9.4) with amino acid
      substitution p.V95A on the risk haplotype harboring HLA-DPB1*13:01. No identical
      variant in the other haplotype including DPB1*09:01 was observed, though that
      haplotype also showed a significant association (P = 8.5 * 10-22; OR = 4.3) with
      systemic sclerosis. Furthermore, the number of risk factors was shown to be a
      predominant factor, as individuals with two factors had elevated risk (P = 6.7 *
      10-13; OR = 30.2). We concluded that RXRB may be involved in antifibrotic
      activity in skin and chromatin remodeling.

PMID- 28506630
TI  - Cost-effective HIV-1 virological monitoring in resource-limited settings using a
      modified commercially available qPCR RNA assay.
AB  - Virological monitoring through plasma viral load (PVL) quantification is
      essential for clinical management of HIV patients undergoing antiretroviral
      treatment (ART), and for detecting treatment failure. Quantitative PCR (qPCR)
      based tests are the gold standard for measuring PVL. Largely because of their
      high cost, however, implementation of these tests in low- and middle-income
      countries fails to cover the testing demand. In this study, we aimed at reducing
      the running cost of the commercially available Abbott RealTimeTM HIV-1 assay by
      minimizing the reagent consumption. To this end, a modified version of the assay
      was obtained by reducing the assay's reagents volume to about a half, and
      validated using a panel of 104 plasma samples. Compared to the standard version,
      the modified Abbott assay allowed for a 50% reduction in running costs. At the
      same time, it showed a 100% concordance in identifying samples with detectable
      viral load, strong correlation (Pearson's r=0.983, P<0.0001), and a high
      agreement between PVL values (mean percent difference between PVL values+/
      standard deviation=0.76+/-3.18%). In detecting viral failure (PVL>1000copiesmL
      1), the modified assay showed a sensitivity of 94.6%, a specificity of 93.8%, and
      a negative and positive predictive values of 93.8% and 94.6%, respectively. The
      modified assay therefore reliably quantifies PVL, predicts viral failure, and
      allows for a ca. 50% reduction in the assay's running costs. It may thus be
      implemented as an ART monitoring tool in resource-limited settings and for
      research purposes.

PMID- 28506631
TI  - Susceptibility of neuroblastoma cells to rabies virus may be affected by passage
      number.
AB  - Maintaining a healthy, continuous immortalized cell line is essential for rabies
      laboratories that perform virus isolation assays and test for the presence of
      viral neutralizing antibodies. Individuals who routinely work with rabies virus,
      such as rabies laboratory employees, or those who may have a high potential for
      exposure to rabies virus, including veterinarians, should be tested for the
      presence of anti-rabies viral neutralizing antibodies (VNA) every 6-24 months,
      depending on potential exposure level. The gold standard for serum neutralization
      assays require the use of live rabies virus and cells that are sensitive to
      rabies virus infection. Additionally, virus isolation assays are routinely
      performed in rabies laboratories as a back-up for the direct fluorescent antibody
      test (dFAT). Currently there are no guidelines or publications recommending the
      use of low, intermediate, or high passage cell lines in rabies assays. In this
      study, we compared the sensitivity of intermediate, high, and extremely high
      passaged neuroblastomas to rabies virus using virus isolation, serum
      neutralization, and real time RT-PCR techniques. Additionally, cells were
      examined microscopically to determine changes in morphology and dissemination of
      rabies virus antigen between intermediate, high, and extremely high passage
      cells. No significant difference was found between cell passage numbers and viral
      susceptibility between intermediate and high passaged cells. However, extremely
      high passaged cells (>=1200 passages) were less susceptible to viral infection
      and/or produced less virus following inoculation. As a result, rabies
      laboratories that use viral isolation and serum neutralization assays should
      regularly assess cell susceptibility to ensure the integrity and repeatability of
      the test.

PMID- 28506632
TI  - Evaluation of HBsAg and anti-HBc assays in saliva and dried blood spot samples
      according HIV status.
AB  - Influence of HIV status in HBV markers detection in saliva and dried blood spots
      (DBS) was not well established. This study aims to evaluate the performance of
      optimized commercial immunoassay for identifying HBsAg and anti-HBc in saliva and
      DBS according HIV status. A sum of 535 individuals grouped as HIV+, HBV+,
      HIV/HBV+ and HIV/HBV- were recruited where 347 and 188 were included for HBsAg
      and anti-HBc evaluation, respectively. Serum, DBS collected in Whatman 903 paper
      and saliva obtained using salivette device were analyzed using EIA. Increased
      sample volume and ROC curve analysis for cut off determination were used for DBS
      and saliva testing. HBsAg detection in saliva and DBS exhibited sensitivities of
      80.9% and 85.6% and specificities of 86.8% and 96.3%. Sensitivity of anti-HBc in
      saliva and DBS were 82.4% and 76.9% and specificities in saliva and DBS were
      96.9% and 91.7%. Low sensitivities were observed for HBsAg (62%) and anti-HBc
      (47%) detection in saliva of HIV/HBV+ individuals. OD values were also lower for
      HBsAg detection in DBS and saliva of HIV/HBV+ individuals compared to their serum
      samples. Statistical significance was found for sensitivities in HBsAg detection
      between saliva and DBS demonstrating high sensitivity for DBS specimens. In
      conclusion, HIV status or antiretroviral treatment appears to interfere in the
      performance of HBsAg and anti-HBc detection in DBS and saliva samples using the
      adapted commercial EIA.

PMID- 28506633
TI  - [Anaerobiospirillum succiniciproducens and Desulfovibrio desulfuricans in 2 cases
      of insidious bacteremia].
AB  - Two cases of insidious bacteremia by uncommon curve and spiral-shaped, motile
      anaerobic gram-negative rods are presented. Both of them were of an unclear
      origin and occurred in immunosuppressed patients with simultaneous diseases. The
      key tests for the identification of Anaerobiospirillum were its micromorphology,
      a strictly anaerobic condition, negative catalase activity, the special-potency
      disk profile, glucose fermentation, and beta-NAG production. Desulfovibrio
      species was identified by all the above preliminary tests but with a different
      disk profile, as well as for being asaccharolytic and desulfoviridin and H2S
      producer. We here alert about the resistance or intermediate susceptibility of
      Anaerobiospirillum succiniciproducens against antimicrobial agents, such as
      metronidazole, one of the first-line drugs used for the treatment of anaerobic
      gram-negative infections. Aminopenicillins with beta-lactamase-inhibitor
      combinations and imipenem were active for this agent. Desulfovibrio desulfuricans
      was beta-lactamase producer and resistant to cephalosporins, while metronidazole,
      imipenem and levofloxacin were active. A reliable identification of these
      microorganisms is important for establishing the best therapeutic scheme.

PMID- 28506634
TI  - [Antimicrobial susceptibility of Helicobacter pylori strains isolated from
      gastric lesions].
AB  - Antimicrobial susceptibility was evaluated by two diffusion methods: E-test
      strips to determine minimum inhibitory concentration (MIC) and disk diffusion for
      amoxicillin, clarithromycin, metronidazole and ciprofloxacin in 30 Helicobacter
      pylori strains isolated from gastric biopsies. No strains were resistant to
      amoxicillin, 17% (5/30) were resistant to clarithromycin, 20% (6/30)
      ciprofloxacin by both methods, and 37% (11/30) to metronidazole by the E-test.
      Although the number of strains studied was reduced, there was a single mismatch
      in interpreting susceptibility when both methods were compared; the same mismatch
      was observed for metronidazole, being categorized as sensitive by the E-test and
      as intermediate by disk diffusion. No association between the histological type
      of lesion and the resistance pattern found could be determined.

PMID- 28506636
TI  - Multiple DNA Interactions Contribute to the Initiation of Telomerase Elongation.
AB  - Telomerase maintains telomere length and chromosome integrity by adding short
      tandem repeats of single-stranded DNA to the 3' ends, via reverse transcription
      of a defined template region of its RNA subunit. To further understand the
      telomerase elongation mechanism, we studied the primer utilization and extension
      activity of the telomerase from the budding yeast Naumovozyma castellii
      (Saccharomyces castellii), which displays a processive nucleotide and repeat
      addition polymerization. For the efficient initiation of canonical elongation,
      telomerase required 4-nt primer 3' end complementarity to the template RNA. This
      DNA-RNA hybrid formation was highly important for the stabilization of an
      initiation-competent telomerase-DNA complex. Anchor site interactions with the
      DNA provided additional stabilization to the complex. Our studies indicate three
      additional separate interactions along the length of the DNA primer, each
      providing different and distinct contributions to the initiation event. A
      sequence-independent anchor site interaction acts immediately adjacent to the
      base-pairing 3' end, indicating a protein anchor site positioned very close to
      the catalytic site. Two additional anchor regions further 5' on the DNA provide
      sequence-specific contributions to the initiation of elongation. Remarkably, a
      non-telomeric sequence in the distal 25- to 32-nt region negatively influences
      the initiation of telomerase elongation, suggesting an anchor site with a
      regulatory role in the telomerase elongation decision.

PMID- 28506635
TI  - CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody-Antigen
      Interface.
AB  - Structure-based vaccine design depends on extensive structural analyses of
      antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can
      circumvent some of the problems of x-ray crystallography as a pipeline for
      obtaining the required structures. We have examined the potential of single
      particle cryoEM for determining the structure of influenza-virus hemagglutinin
      (HA):single-chain variable-domain fragment complexes, by studying a complex we
      failed to crystallize in pursuing an extended project on the human immune
      response to influenza vaccines.The result shows that a combination of cryoEM and
      molecular modeling can yield details of the antigen-antibody interface, although
      small variation in the twist of the rod-likeHA trimer limited the overall
      resolution to about 4.5A.Comparison of principal 3D classes suggests ways to
      modify the HA trimer to overcome this limitation. A closely related antibody from
      the same donor did yield crystals when bound with the same HA, giving us an
      independent validation of the cryoEM results.The two structures also augment our
      understanding of receptor-binding site recognition by antibodies that neutralize
      a wide range of influenza-virus variants.

PMID- 28506637
TI  - Thiamine and benfotiamine prevent stress-induced suppression of hippocampal
      neurogenesis in mice exposed to predation without affecting brain thiamine
      diphosphate levels.
AB  - Thiamine is essential for normal brain function and its deficiency causes
      metabolic impairment, specific lesions, oxidative damage and reduced adult
      hippocampal neurogenesis (AHN). Thiamine precursors with increased
      bioavailability, especially benfotiamine, exert neuroprotective effects not only
      for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As
      it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice
      to predator stress for 5 consecutive nights and studied the proliferation (number
      of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn
      immature neurons in the subgranular zone of the dentate gyrus. In stressed mice,
      the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed
      animals. This reduction was prevented when the mice were treated (200mg/kg/day in
      drinking water for 20days) with thiamine or benfotiamine, that were recently
      found to prevent stress-induced behavioral changes and glycogen synthase kinase
      3beta (GSK-3beta) upregulation in the CNS. Moreover, we show that thiamine and
      benfotiamine counteract stress-induced bodyweight loss and suppress stress
      induced anxiety-like behavior. Both treatments induced a modest increase in the
      brain content of free thiamine while the level of thiamine diphosphate (ThDP)
      remained unchanged, suggesting that the beneficial effects observed are not
      linked to the role of this coenzyme in energy metabolism. Predator stress
      increased hippocampal protein carbonylation, an indicator of oxidative stress.
      This effect was antagonized by both thiamine and benfotiamine. Moreover, using
      cultured mouse neuroblastoma cells, we show that in particular benfotiamine
      protects against paraquat-induced oxidative stress. We therefore hypothesize that
      thiamine compounds may act by boosting anti-oxidant cellular defenses, by a
      mechanism that still remains to be unveiled. Our study demonstrates, for the
      first time, that thiamine and benfotiamine prevent stress-induced inhibition of
      hippocampal neurogenesis and accompanying physiological changes. The present data
      suggest that thiamine precursors with high bioavailability might be useful as a
      complementary therapy in several neuropsychiatric disorders.

PMID- 28506638
TI  - Ionic liquid-based reagents improve the stability of midterm fecal sample
      storage.
AB  - Fecal samples are widely used in metagenomic research, which aims to elucidate
      the relationship between human health and the intestinal microbiota. However, the
      best conditions for stable and reliable storage and transport of these samples at
      room temperature are still unknown, and whether samples stored at room
      temperature for several days will maintain their microbiota composition is still
      unknown. Here, we established and tested a preservation method using reagents
      containing imidazolium- or pyridinium-based ionic liquids. We stored human fecal
      samples in these reagents for up to 7 days at different temperatures.
      Subsequently, all samples were sequenced and compared with fresh samples and/or
      samples treated under other conditions. The 16S rRNA sequencing results suggested
      that ionic liquid-based reagents could stabilize the composition of the
      microbiota in fecal samples during a 7-day storage period, particularly when
      stored at room temperature. Thus, this method may have implications in the
      storage of fecal samples for metagenomic research.

PMID- 28506639
TI  - Increased C-reactive protein plasma levels are not involved in the onset of post
      operative atrial fibrillation.
AB  - BACKGROUND: Increased inflammation biomarkers plasma levels, including C-reactive
      protein (CRP), have been associated with the initiation and perpetuation of
      atrial fibrillation (AF). However, it is not known whether an increased CRP
      plasma level, without concomitant inflammation, is sufficient to induce AF. We
      investigated whether higher CRP plasma levels, determined by the presence of
      +219G>A CRP gene polymorphism, is associated with an increased risk of post
      operative AF. METHODS: One hundred and fifteen adult patients submitted to
      elective coronary surgery were genotyped for the CRP +219G>A polymorphism. CRP
      plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: CRP
      plasma levels before surgery were higher in GG than in GA+AA patients (3.4+/-3.1
      vs. 1.7+/-1.8, p<0.015). Thirteen percent of the patients presented post
      operative AF. Despite the positive correlation between the polymorphism and CRP
      levels, there was no significant difference in the occurrence of post-operative
      AF between the different genotypes. CONCLUSIONS: These results suggest that
      increased CRP plasma levels that are not associated with an inflammatory process
      are not sufficient to trigger AF after cardiac surgery.

PMID- 28506640
TI  - Diagnostic accuracy of the Embolic Risk French Calculator for symptomatic
      embolism with infective endocarditis among Japanese population.
AB  - BACKGROUND: Recently, the Embolic Risk French Calculator (ER-Calculator) was
      designed to predict symptomatic embolism (SE) associated with infective
      endocarditis (IE), but external validation has not been reported. This study
      aimed to determine predictors of SE and the diagnostic accuracy of the ER
      Calculator in left-sided active IE among a Japanese population. METHODS: This
      retrospective cohort study included 166 consecutive patients with a definite
      diagnosis of left-sided IE from 1994 to 2015 in our institution. SE during the
      period after initiation of antibiotic therapy was defined as new SE and embolism
      during the period before initiation of antibiotic therapy was defined as previous
      embolism. The primary endpoint was new SE. RESULTS: The mean age of patients was
      63+/-17 years. New SE occurred in 23 (14%) patients at a median of 6 days
      (interquartile range: 2.5-12.5 days) after initiation of antibiotic therapy. The
      cumulative incidence of new SE at 12 weeks was 18.2%. The 2-week probability by
      the ER-Calculator as well as previously reported predictors, such as previous
      embolism, vegetation length (>10mm), and their combination, were associated with
      a high risk of new SE. By receiver operating characteristic analysis, the area
      under the curve of the 2-week probability by the ER-Calculator for prediction of
      new SE was 0.75 and the optimal cut-off value was 8%. A 2-week probability >8% by
      the ER-Calculator was the most useful predictor of new SE (hazard ratio 3.63, 95%
      confidence interval 1.50-8.37; p=0.006), which was more remarkable for fatal
      embolic events (hazard ratio 13.9, 95% confidence interval 3.19-95.4; p=0.004).
      CONCLUSIONS: The ER-Calculator is a useful predictor of new SE. Predictive
      ability is more remarkable for critical embolic events.

PMID- 28506641
TI  - Guiding multimodal registration with learned optimization updates.
AB  - In this paper, we address the multimodal registration problem from a novel
      perspective, aiming to predict the transformation aligning images directly from
      their visual appearance. We formulate the prediction as a supervised regression
      task, with joint image descriptors as input and the output are the parameters of
      the transformation that guide the moving image towards alignment. We model the
      joint local appearance with context aware descriptors that capture both local and
      global cues simultaneously in the two modalities, while the regression function
      is based on the gradient boosted trees method capable of handling the very large
      contextual feature space. The good properties of our predictions allow us to
      couple them with a simple gradient-based optimization for the final registration.
      Our approach can be applied to any transformation parametrization as well as a
      broad range of modality pairs. Our method learns the relationship between the
      intensity distributions of a pair of modalities by using prior knowledge in the
      form of a small training set of aligned image pairs (in the order of 1-5 in our
      experiments). We demonstrate the flexibility and generality of our method by
      evaluating its performance on a variety of multimodal imaging pairs obtained from
      two publicly available datasets, RIRE (brain MR, CT and PET) and IXI (brain MR).
      We also show results for the very challenging deformable registration of
      Intravascular Ultrasound and Histology images. In these experiments, our approach
      has a larger capture range when compared to other state-of-the-art methods, while
      improving registration accuracy in complex cases.

PMID- 28506642
TI  - No-waiting dentine self-etch concept-Merit or hype.
AB  - OBJECTIVE: A recently-launched universal adhesive, G-Premio Bond, provides
      clinicians with the alternative to use the self-etch technique for bonding to
      dentine without waiting for the adhesive to interact with the bonding substrate
      (no-waiting self-etch; Japanese brochure), or after leaving the adhesive
      undisturbed for 10s (10-s self-etch; international brochure). The present study
      was performed to examine in vitro performance of this new universal adhesive
      bonded to human coronal dentine using the two alternative self-etch modes.
      METHODS: One hundred and ten specimens were bonded using two self-etch
      application modes and examined with or without thermomechanical cycling (10,000
      thermal cycles and 240,000 mechanical cycles) to simulate one year of intraoral
      functioning. The bonded specimens were sectioned for microtensile bond testing,
      ultrastructural and nanoleakage examination using transmission electron
      microscopy. Changes in the composition of mineralised dentine after adhesive
      application were examined using Fourier transform infrared spectroscopy. RESULTS:
      Both reduced application time and thermomechanical cycling resulted in
      significantly lower bond strengths, thinner hybrid layers, and significantly more
      extensive nanoleakage after thermomechanical cycling. Using the conventional 10-s
      application time improved bonding performance when compared with the no-waiting
      self-etch technique. Nevertheless, nanoleakage was generally extensive under all
      testing parameters employed for examining the adhesive. CONCLUSION: Although
      sufficient bond strength to dentine may be achieved using the present universal
      adhesive in the no-waiting self-etch mode that does not require clinicians to
      wait prior to polymerisation of the adhesive, this self-etch concept requires
      further technological refinement before it can be recommended as a clinical
      technique. CLINICAL SIGNIFICANCE: Although the surge for cutting application time
      to increase user friendliness remains the most frequently sought conduit for
      advancement of dentine bonding technology, the use of the present universal
      adhesive in the no-waiting self-etch mode may not represent the best use of the
      adhesive.

PMID- 28506643
TI  - Epithelial basement membrane injury and regeneration modulates corneal fibrosis
      after pseudomonas corneal ulcers in rabbits.
AB  - The purpose of this study was to investigate whether myofibroblast-related
      fibrosis (scarring) after microbial keratitis was modulated by the epithelial
      basement membrane (EBM) injury and regeneration. Rabbits were infected with
      Pseudomonas aeruginosa after epithelial scrape injury and the resultant severe
      keratitis was treated with topical tobramycin. Corneas were analyzed from one to
      four months after keratitis with slit lamp photos, immunohistochemistry for alpha
      smooth muscle actin (alpha-SMA) and monocyte lineage marker CD11b, and
      transmission electron microscopy. At one month after keratitis, corneas had no
      detectible EBM lamina lucida or lamina densa, and the central stroma was packed
      with myofibroblasts that in some eyes extended to the posterior corneal surface
      with damage to Descemet's membrane and the endothelium. At one month, a nest of
      stromal cells in the midst of the SMA + myofibroblasts in the stroma that were
      CD11b+ may be fibrocyte precursors to myofibroblasts. At two to four months after
      keratitis, the EBM fully-regenerated and myofibroblasts disappeared from the
      anterior 60-90% of the stroma of all corneas, except for one four-month post
      keratitis cornea where anterior myofibroblasts were still present in one
      localized pocket in the cornea. The organization of the stromal extracellular
      matrix also became less disorganized from two to four months after keratitis but
      remained abnormal compared to controls at the last time point. Myofibroblasts
      persisted in the posterior 10%-20% of posterior stroma even at four months after
      keratitis in the central cornea where Descemet's membrane and the endothelium
      were damaged. This study suggests that the EBM has a critical role in modulating
      myofibroblast development and fibrosis after keratitis-similar to the role of EBM
      in fibrosis after photorefractive keratectomy. Damage to EBM likely allows
      epithelium-derived transforming growth factor beta (TGFbeta) to penetrate the
      stroma and drive development and persistence of myofibroblasts. Eventual repair
      of EBM leads to myofibroblast apoptosis when the cells are deprived of requisite
      TGFbeta to maintain viability. The endothelium and Descemet's membrane may serve
      a similar function modulating TGFbeta penetration into the posterior stroma-with
      the source of TGFbeta likely being the aqueous humor.

PMID- 28506644
TI  - Affinity purification of Car9-tagged proteins on silica matrices: Optimization of
      a rapid and inexpensive protein purification technology.
AB  - Car9, a dodecapeptide identified by cell surface display for its ability to bind
      to the edge of carbonaceous materials, also binds to silica with high affinity.
      The interaction can be disrupted with l-lysine or l-arginine, enabling a broad
      range of technological applications. Previously, we reported that C-terminal Car9
      extensions support efficient protein purification on underivatized silica. Here,
      we show that the Car9 tag is functional and TEV protease-excisable when fused to
      the N-termini of target proteins, and that it supports affinity purification
      under denaturing conditions, albeit with reduced yields. We further demonstrate
      that capture of Car9-tagged proteins is enhanced on small particle size silica
      gels with large pores, that the concomitant problem of nonspecific protein
      adsorption can be solved by lysing cells in the presence of 0.3% Tween 20, and
      that efficient elution is achieved at reduced l-lysine concentrations under
      alkaline conditions. An optimized small-scale purification kit incorporating the
      above features allows Car9-tagged proteins to be inexpensively recovered in
      minutes with better than 90% purity. The Car9 affinity purification technology
      should prove valuable for laboratory-scale applications requiring rapid access to
      milligram-quantities of proteins, and for preparative scale purification schemes
      where cost and productivity are important factors.

PMID- 28506645
TI  - Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in
      cancer biology-Involvement in tumour suppression, tumour growth, multidrug
      resistance and target for chemotherapy.
AB  - Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all
      human cells. It catalyses the glutathione-dependent removal of the endogenous
      reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side
      product of anaerobic glycolysis. It modifies protein and DNA to form mainly
      hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal
      accumulation of MG, dicarbonyl stress, increases adduct levels which may induce
      apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a
      tumour suppressor protein and small molecule inducers of Glo1 expression may find
      use in cancer prevention. Increased Glo1 expression is permissive for growth of
      tumours with high glycolytic activity and is thereby a biomarker of tumour
      growth. High Glo1 expression is a cause of multi-drug resistance. It is produced
      by over-activation of the Nrf2 pathway and GLO1 amplification. Glo1 inhibitors
      are antitumour agents, inducing apoptosis and necrosis, and anoikis. Tumour stem
      cells and tumours with high flux of MG formation and Glo1 expression are
      sensitive to Glo1 inhibitor therapy. It is likely that MG-induced cell death
      contributes to the mechanism of action of current antitumour agents. Common
      refractory tumours have high prevalence of Glo1 overexpression for which Glo1
      inhibitors may improve therapy.

PMID- 28506646
TI  - Virtual Resting Pd/Pa From Coronary Angiography and Blood Flow Modelling:
      Diagnostic Performance Against Fractional Flow Reserve.
AB  - BACKGROUND: Fractional flow reserve (FFR) has been established as a useful
      diagnostic tool. The distal coronary pressure to aortic pressure (Pd/Pa) ratio at
      rest is a simpler physiologic index but also requires the use of the pressure
      wire, whereas recently proposed virtual functional indices derived from coronary
      imaging require complex blood flow modelling and/or are time-consuming. Our aim
      was to test the diagnostic performance of virtual resting Pd/Pa using routine
      angiographic images and a simple flow model. METHODS: Three-dimensional
      quantitative coronary angiography (3D-QCA) was performed in 139 vessels (120
      patients) with intermediate lesions assessed by FFR. The resting Pd/Pa for each
      lesion was assessed by computational fluid dynamics. RESULTS: The discriminatory
      power of virtual resting Pd/Pa against FFR (reference: <=0.80) was high (area
      under the receiver operator characteristic curve [AUC]: 90.5% [95% CI: 85.4
      95.6%]). Diagnostic accuracy, sensitivity and specificity for the optimal virtual
      resting Pd/Pa cut-off (<=0.94) were 84.9%, 90.4% and 81.6%, respectively. Virtual
      resting Pd/Pa demonstrated superior performance (p<0.001) versus 3D-QCA %area
      stenosis (AUC: 77.5% [95% CI: 69.8-85.3%]). There was a good correlation between
      virtual resting Pd/Pa and FFR (r=0.69, p<0.001). CONCLUSIONS: Virtual resting
      Pd/Pa using routine angiographic data and a simple flow model provides fast
      functional assessment of coronary lesions without requiring the pressure-wire and
      hyperaemia induction. The high diagnostic performance of virtual resting Pd/Pa
      for predicting FFR shows promise for using this simple/fast virtual index in
      clinical practice.

PMID- 28506647
TI  - Acute Structural Failure of the Trifecta Aortic Valve Bioprosthesis.
AB  - Advancements in bioprosthetic valve technology have greatly enhanced the
      haemodynamic performance and long-term durability of tissue valves. These
      features, along with the key advantage of avoiding lifelong anticoagulation, have
      made bioprosthetic valves increasingly attractive for clinicians and patients
      alike. The St Jude Trifecta valve is a novel, bovine pericardial bioprosthesis
      with promising early data for performance and safety. However, no prosthetic
      valve is perfect and prosthesis failure can occur with even the most reliable and
      well-designed devices. We report a case of early and acute structural
      deterioration (stent-post leaflet rupture) of the Trifecta valve, explanted after
      33 months, in a 76-year-old male.

PMID- 28506648
TI  - Antegrade Versus Continuous Retrograde del Nido Cardioplegia in the David I
      Operation.
AB  - BACKGROUND: The efficacy of continuous retrograde del Nido cardioplegia for
      myocardial protection is still controversial. We hypothesised that antegrade and
      retrograde cardioplegia offer equivalent safety for myocardial protection in the
      David I procedure. METHODS: We retrospectively reviewed 33 patients undergoing
      the David I operation with antegrade or retrograde del Nido solution from June
      2014 to January 2016. The outcomes were compared. The follow-up was 1 month to 15
      months. RESULTS: There was no hospital mortality or reoperation in both groups.
      Cardiopulmonary bypass, and aortic clamp times were similar. Troponin I level
      (TnI), creatine kinase level (CKMB), left ventricular ejection fraction (LVEF),
      ventilation times, intensive care unit (ICULOS) and hospital stay times (THLOS)
      were similar between the two groups. The lactate level was slightly higher
      (9.26+/-2.56 vs 7.17+/-1.58, p=0.01) in the antegrade group compared with the
      retrograde group. The incidence of heart block was higher (four patients) in the
      retrograde group (26.7% vs 0%, p=0.019). Only one patient (6.7%) required
      implantation of a permanent cardiac pacemaker. CONCLUSION: Antegrade and
      continuous retrograde del Nido cardioplegia can be used safely and effectively in
      the David I operation. The continuous retrograde del Nido cardioplegia is
      associated with a higher rate of temporary AV block which does not require
      permanent pacing, and a lower lactate level.

PMID- 28506649
TI  - Dose optimization in cardiac CT.
AB  - Rapid progress in the field of Cardiac CT is fostered by the advances in CT
      scanner technology as well as multiple clinical trials demonstrating its role in
      coronary artery disease and other indications like congenital heart disease,
      pulmonary vein assessment and pre transcatheter aortic valve replacement. The
      cardiovascular imager today is responsible for delivering diagnostic image
      quality while striking a balance with optimized radiation dose. Radiation dose is
      the result of multiple scanner and patient related factors. Achieving a
      justifiable radiation dose according to the ALARA principle requires an adept
      understanding of the factors affecting radiation dose. We review different scan
      factors and their effect on radiation dose and present strategies for radiation
      dose optimization in cardiac CT.

PMID- 28506651
TI  - A load-to-fracture and strain analysis of monolithic zirconia cantilevered
      frameworks.
AB  - STATEMENT OF PROBLEM: The dimensions of implant-supported fixed cantilevered
      prostheses are important to prevent mechanical and biological complications.
      Information on the optimum thickness and cantilever length for improving the
      strength of zirconia cantilevered frameworks is limited in the literature.
      PURPOSE: The purpose of this in vitro study was to investigate the effect of
      cantilever length and occlusocervical thickness on the load-to-fracture and
      strain distribution of zirconia frameworks. MATERIAL AND METHODS: Twenty-seven
      rectangular prism-shaped specimens (6 mm thick buccolingually) were fabricated
      using a computer-aided design and computer-aided manufacturing (CAD-CAM) milling
      technique. The specimens were prepared in 9 groups (n=3) according to their
      vertical dimensions (6*6 mm, 8*6 mm, and 10*6 mm) and cantilever loading distance
      (7 mm, 10 mm, and 17 mm). All specimens were heat treated in a porcelain furnace
      and thermocycled for 20000 cycles before the tests. Each framework was secured
      using a clamp attached to the first 20 mm of the framework. A 3-dimensional image
      correlation technique was used for a full-field measurement of strain during
      testing. A load-to-fracture test was used until the specimens fractured. Maximum
      force and principal strain data were analyzed by 2-way analysis of variance using
      the maximum likelihood estimation method (alpha=.05). RESULTS: No statistically
      significant effects (P>.05) were found for occlusocervical thickness and
      cantilever length or between them on the strain distribution. The results showed
      that the effect of occlusocervical thickness and cantilever length was
      significant on the load to fracture (P<.001). No statistically significant
      interaction was observed between the 2 factors (P>.05). CONCLUSIONS: Increased
      occlusocervical thickness and decreased cantilever length allowed the cantilever
      to withstand higher loads. The occlusocervical thicknesses and cantilever lengths
      of zirconia frameworks tested withstood the maximum reported occlusal force. The
      properties of components in the implant-abutment framework assembly should be
      considered in the interpretation of these results.

PMID- 28506652
TI  - Comparison of denture tooth movement between CAD-CAM and conventional fabrication
      techniques.
AB  - STATEMENT OF PROBLEM: Data comparing the denture tooth movement of computer-aided
      design and computer-aided manufacturing (CAD-CAM) and conventional denture
      processing techniques are lacking. PURPOSE: The purpose of this in vitro study
      was to compare the denture tooth movement of pack-and-press, fluid resin,
      injection, CAD-CAM-bonded, and CAD-CAM monolithic techniques for fabricating
      dentures to determine which process produces the most accurate and reproducible
      prosthesis. MATERIAL AND METHODS: A total of 50 dentures were evaluated, 10 for
      each of the 5 groups. A master denture was fabricated and milled from
      prepolymerized poly(methyl methacrylate). For the conventional processing
      techniques (pack-and-press, fluid resin, and injection) a polyvinyl siloxane
      putty mold of the master denture was made in which denture teeth were placed and
      molten wax injected. The cameo surface of each wax-festooned denture was laser
      scanned, resulting in a standard tessellation language (STL) format file. The CAD
      CAM dentures included 2 subgroups: CAD-CAM-bonded teeth in which the denture
      teeth were bonded into the milled denture base and CAD-CAM monolithic teeth in
      which the denture teeth were milled as part of the denture base. After all
      specimens had been fabricated, they were hydrated for 24 hours, and the cameo
      surface laser scanned. The preprocessing and postprocessing scan files of each
      denture were superimposed using surface-matching software. Measurements were made
      at 64 locations, allowing evaluation of denture tooth movement in a buccal,
      lingual, mesial-distal, and occlusal direction. The use of median and
      interquartile range values was used to assess accuracy and reproducibility.
      Levene and Kruskal-Wallis analyses of variance were used to evaluate differences
      between processing techniques (alpha=.05). RESULTS: The CAD-CAM monolithic
      technique was the most accurate, followed by fluid resin, CAD-CAM-bonded, pack
      and-press, and injection. CAD-CAM monolithic technique was the most reproducible,
      followed by pack-and-press, CAD-CAM-bonded, injection, and fluid resin.
      Techniques involving compression during processing showed increased positive
      occlusal tooth movement compared with techniques not involving compression.
      CONCLUSIONS: CAD-CAM monolithic dentures produced the best combination of
      accuracy and reproducibility of the tested techniques. The results from this
      study demonstrate that varying amounts of tooth movement can be expected
      depending on the processing technique. However, the clinical significance of
      these differences is unknown.

PMID- 28506653
TI  - Inhibition of denture plaque deposition on complete dentures by 2
      methacryloyloxyethyl phosphorylcholine polymer coating: A clinical study.
AB  - STATEMENT OF PROBLEM: Denture plaque-associated infections are regarded as a
      source of serious dental and medical complications in the elderly population.
      Methods of managing this problem are needed. PURPOSE: The purpose of this
      clinical study was to evaluate the effects of treatment with a 2
      methacryloyloxyethyl phosphorylcholine polymer, PMBPAz, on plaque deposition in
      complete dentures. MATERIAL AND METHODS: The study protocol was approved by the
      Ethics Committee of Showa University (#2013-013). Eleven individuals with
      maxillary complete dentures participated in this study. Their dentures were
      treated with PMBPAz, and the amount of denture plaque accumulation was evaluated
      by staining the denture surfaces with methylene blue after 2 weeks of denture
      usage. The same procedures were repeated to evaluate the original denture
      surfaces as a control. The image of the stained denture surface was captured
      using a digital camera, and the percentage of stained area, quantified as a pixel
      based density, of the whole denture area (percentage of plaque index) was
      calculated for the mucosal and polished surfaces. To quantify the biofilm on the
      dentures, denture plaque biofilm was detached by ultrasonic vibration,
      resuspended in diluent, and measured with a microplate reader at an optical
      density of 620 nm. The effects of PMBPAz treatment on these variables were
      statistically analyzed with ANOVA (alpha=.05). RESULTS: The mean +/-SD percentage
      of plaque index was 40.7% +/-19.9% on the mucosal surfaces and 28.0% +/-16.8% on
      the polished surfaces of the control denture. The mean percentage of plaque index
      of PMBPAz-treated dentures significantly decreased to 17.4%% +/-12.0% on the
      mucosal surfaces (P<.001) and 15.0% +/-9.9% on the polished surfaces (P<.05). The
      quantification of plaque deposition agreed with the results of these image
      analyses. CONCLUSIONS: These results demonstrated the effectiveness of the
      treatment with the PMBPAz to inhibit the bacterial plaque deposition on complete
      dentures.

PMID- 28506654
TI  - Effect of number of firings on the color and translucency of ceramic core
      materials with veneer ceramic of different thicknesses.
AB  - STATEMENT OF PROBLEM: Whether masking or translucency should be the goal for
      achieving an esthetic restoration with ceramic materials is unknown. PURPOSE: The
      purpose of this in vitro study was to examine the effect of the number of firings
      on the color and translucency of ceramic core material with different thicknesses
      of veneer ceramic. MATERIAL AND METHODS: Three different ceramic systems were
      used: IPS Empress (IE), IPS e.max Press (IEP), and Turkom Cera (TC). Ninety disk
      shaped cores, 10 mm in diameter and 0.8 mm in thickness were prepared using each
      system (n=30). The specimens were divided into 3 subgroups (n=10) according to
      the thickness of the veneering ceramic: 0.5, 1.0, and 1.5 mm. The specimens were
      fired 1, 3, and 5 times, and the color parameters of the specimens were measured.
      The color measurements were repeated, and the data were statistically evaluated
      using 2-way and multifactorial analysis of variance, the Duncan test, and the
      Bonferroni post hoc test. RESULTS: The number of firings affected the
      translucency parameter and CIELab values. Increased porcelain thickness led to
      decreased translucency parameter and L* values and increased a* and b* values
      (P<.05). The IE system was the most translucent (P<.001). The changes with
      increased firing periods were not statistically significant (P>.05). The number
      of firings affected the color change of the IE and IEP systems but not of the
      translucency parameter system. CONCLUSIONS: Repeated firings and porcelain
      thickness affected the final color and translucency of the ceramic systems
      tested. These 2 factors adversely affected the esthetic result and should be
      considered in both the preparation and the laboratory phase.

PMID- 28506655
TI  - Fiber-reinforced composite fixed dental prostheses: A 4-year prospective clinical
      trial evaluating survival, quality, and effects on surrounding periodontal
      tissues.
AB  - STATEMENT OF PROBLEM: Although fiber-reinforced composite fixed dental prostheses
      (FRC FDPs) are a reliable treatment option for the restoration of single missing
      teeth, comparatively few prospective clinical trials (PCT) exist. PURPOSE: The
      purpose of this PCT was to evaluate the survival, quality outcome, and effect of
      FRC FDPs on periodontal health over 4 years. MATERIAL AND METHODS: Twenty-six
      consecutive patients (16 men, 10 women) receiving FRC FDPs with preimpregnated
      unidirectional fiber reinforcement were included in the trial. Eighteen FRC FDPs
      were placed in the maxilla and 8 in the mandible. Data from baseline, 12-, 36-,
      and 48-months of follow-up were recorded, and the prostheses were classified as
      "success," "survival," or "failure." Periodontal parameters (probing depth,
      clinical attachment level, plaque index, and bleeding index were assessed, and
      the quality was rated according to modified United States Public Health Service
      (USPHS)/Ryge or World Dental Federation (FDI) criteria. RESULTS: Functional
      survival at 4 years was 73.5% (95% confidence interval [CI], 52.9-87.3) with 17
      FRC FDPs still functioning. Twelve of these were classified as "success" and 5 as
      "survival." Overall survival was 53.0% (95% CI, 30.4-74.4). Six FRC FPDs failed
      completely. Periodontal parameters did not change over the observation period.
      Regression analysis showed that probing depth and clinical attachment level did
      not influence the survival of FRC FDPs. According to USPHS/Ryge/FDI criteria only
      "wear" and "surface luster" increased significantly over 4 years. CONCLUSIONS:
      The survival rate of FRC FPDs confirms existing data. Negative effects on
      periodontal health were not seen over the period of observation. Aging effects
      such as wear were recorded and indicated that FRC FPDs are at risk of
      disintegration, as they are composed of a fiber framework and veneering composite
      resin.

PMID- 28506656
TI  - Colorizing titanium-6aluminum-4vanadium alloy using electrochemical anodization:
      Developing a color chart.
AB  - Colorizing titanium alloys by electrochemical anodization is used in dentistry
      especially for identification purposes. Colorization is the result of distinct
      voltage applications to specific titanium alloys when placed in an electrolyte.
      Titanium and titanium alloys differ in their ability to be anodized. As titanium
      6aluminum-4vanadium is commonly used as an abutment material, we have developed a
      specific color reference scale relating color to the voltage applied.

PMID- 28506658
TI  - [Cognitive neuroscience of aging: explanatory models].
AB  - The aim of the cognitive neuroscience of aging is the study of brain activity and
      the cognitive processes associated with age. In order to understand the dynamics
      of neurocognitive activity in older people, the present review highlights four
      explanatory models. The first one (HAROLD) highlights brain bilaterality, mainly
      in the pre-frontal cortex. The second paradigm (PASA) places special emphasis on
      neuronal polarisation (anterior-posterior). The third model (CRUNCH) relates the
      manifest activity of the brain to the level of complexity of the task. The last
      one (ELSA) emphasises the spatial and temporal distribution of brain activity in
      the different phases of recovery. Although different in their content, the four
      explanatory models are perfectly compatible with the findings reported by
      neuroimaging techniques, suggesting the use of compensation strategies and
      cognitive reserve for interventions that may help to optimise the performance of
      older people.

PMID- 28506659
TI  - Comparison of density and output of sweat gland in tropical Africans and
      temperate Koreans.
AB  - Modification of sweating could be due to changes in activated sweat gland density
      (ASGD) and/or activated sweat gland output (ASGO). The present study determined
      regional and inter-ethnic differences in ASGD and ASGO during passive heating
      between tropical natives (African, n=22) and temperate natives (Republic of
      Korean, n=25). Heat load was carried out by immersing the half body into a hot
      water bath for 30min. Tympanic temperature (Tty) and skin temperature (Ts) were
      measured. Mean body temperature (mTb) was calculated. Sudomotor activities
      including sweat onset time, sweat rate, ASGD, and ASGO were examined in eight
      regions of the skin. Africans had smaller increase in mTb during passive heating
      than Koreans. The onset time of sweating was much more delayed in Africans
      compared to Koreans. In response to thermal load, ASGD and ASGO differed between
      body regions in Africans and Koreans. In most skin regions, ASGD and ASGO were
      lower in tropical Africans compared to those in temperate Koreans. Trunk portion
      including chest, upper back, lower back, abdomen had greater swear rate, ASGD,
      and ASGO compared to peripheral segments including upper arm, forearm, leg, and
      thigh in both ethnic groups. Distribution patterns of ASGD over the body appeared
      to be similar in both Africans and Koreans at the peak of thermal loading. In
      conclusion, the present study demonstrates that sudomotor activity in tropical
      Africans is reduced with lower ASGD and ASGO over the body surface compared to
      temperate Koreans.

PMID- 28506657
TI  - Understanding pre-mRNA splicing through crystallography.
AB  - Crystallography is a powerful tool to determine the atomic structures of proteins
      and RNAs. X-ray crystallography has been used to determine the structure of many
      splicing related proteins and RNAs, making major contributions to our
      understanding of the molecular mechanism and regulation of pre-mRNA splicing.
      Compared to other structural methods, crystallography has its own advantage in
      the high-resolution structural information it can provide and the unique
      biological questions it can answer. In addition, two new crystallographic methods
      - the serial femtosecond crystallography and 3D electron crystallography - were
      developed to overcome some of the limitations of traditional X-ray
      crystallography and broaden the range of biological problems that crystallography
      can solve. This review discusses the theoretical basis, instrument requirements,
      troubleshooting, and exciting potential of these crystallographic methods to
      further our understanding of pre-mRNA splicing, a critical event in gene
      expression of all eukaryotes.

PMID- 28506660
TI  - Specific clones of Staphylococcus lugdunensis may be associated with colon
      carcinoma.
AB  - Staphylococcus lugdunensis produces a tannase with activity that may be
      associated with the onset of colon carcinoma. To clarify this feature of colon
      carcinoma-associated S. lugdunensis, we obtained isolates from healthy subjects
      and patients with colon adenomas and carcinomas and analyzed their genetic
      backgrounds. In total, 40 S. lugdunensis isolates from 288 rectal swabs collected
      between 2002 and 2008 were used. These isolates were classified into four groups
      according to the diseases of the subjects: healthy (n=13), colon carcinoma
      (n=13), colon adenoma (n=9), and unknown (n=5). The isolates were also classified
      by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. In
      addition, an antimicrobial susceptibility test and detection of resistance genes
      were performed for all isolates. According to the PFGE analysis, 40 isolates
      could be classified into five groups. Among the groups, carcinoma and colon
      adenoma patients were significantly more frequently (40.9%) classified into group
      D (p<0.05), whereas healthy subjects were more frequently (38.5%) classified into
      group A. All isolates in group D were typed as ST27, which was clearly different
      than isolates in the other groups. All isolates were susceptible to the
      antimicrobial agents tested, including beta-lactams, although seven strains
      produced beta-lactamase. Our data suggest that a specific clone of S. lugdunensis
      might be associated with colon carcinoma and colon adenoma. This clone showed
      high susceptibility to many antimicrobial agents. Therefore, eradication therapy
      may lead to a decreased risk of colon carcinoma.

PMID- 28506661
TI  - TRPA1 receptors in chronic cough.

PMID- 28506662
TI  - Adiponectin down-regulates CREB and inhibits proliferation of A549 lung cancer
      cells.
AB  - INTRODUCTION: Adipokines are known to play a relevant role in a number of cancer
      related molecular pathways. Adiponectin is a major adipokine with anti
      inflammatory and beneficial metabolic actions. Furthermore, it has been shown to
      exert anti-carcinogenic effects in various tumor models and some clinical studies
      suggested an inverse relationship between circulating levels of adiponectin and
      an increased risk for development of malignancies. On the other hand, the cyclic
      AMP response element binding (CREB) transcription factor has been clearly linked
      to lung cancer. METHODS: we analyzed cell proliferation, cell cycle of A549 cells
      treated with adiponectin as well as CREB activation status in human lung
      adenocarcinoma A549 cells and in non-small cell lung cancer (NSCLC) samples.
      RESULTS: adiponectin treatment, at concentrations ranging between 5 and 50 MUg/ml
      mimicking human serum levels, has a significant effect on reducing tumor cell
      proliferation of A549 cells, mainly by altering cell cycle progression.
      Importantly, we provide evidence that adiponectin clearly inhibits in a dose- and
      time-dependent manner CREB phosphorylation (activation) and, at least in part,
      also the level of CREB protein itself, preceding and accompanying the anti
      proliferative effects in response to adiponectin. Moreover, in agreement with
      previous studies demonstrating that CREB over-expression occurs in many tumors,
      we also show by western-blotting from lung specimen that CREB is significantly up
      regulated in NSCLC samples compared to adjacent normal tissues from six patients.
      CONCLUSIONS: Overall, our results represent the first evidence of CREB inhibition
      by adiponectin and may provide new insight into therapeutic strategies for lung
      cancer.

PMID- 28506663
TI  - Cough associated with gastro-oesophageal reflux disease (GORD): Japanese
      experience.
AB  - Differences in the aetiology as well as patient background of chronic cough have
      been recognised among US, UK, and Japan. One of the marked differences has been
      the prevalence of gastro-oesophageal reflux disease (GORD), which has been one of
      the top three causes in Western countries. It was indeed uncommon or rare in
      Japan, but, with the increasing prevalence of GOR itself, chronic cough
      associated with GORD seems to have become more common. In this article, cough
      associated with GORD will be reviewed based on literature and our Japanese
      experience. Further, potentially broader relevance of GORD in chronic cough will
      also be mentioned, highlighting the potential importance of dysmotiliy/non-acid
      reflux.

PMID- 28506664
TI  - Heliox delivered by high flow nasal cannula improves oxygenation in infants with
      respiratory syncytial virus acute bronchiolitis.
AB  - OBJECTIVE: The objective of this study is to evaluate the hypothesis that use of
      heliox would result in improvement of gas exchange when used with high flow nasal
      cannula in infants with RSV acute bronchiolitis. METHODS: All patients that met
      the inclusion criteria were randomized to either heliox (70:30) or air-oxygen
      mixture 30% via high flow nasal cannula at 8L/min for a continuous 24h.
      Measurements were taken at baseline, after 2h, and at the end of the 24h.
      RESULTS: This prospective study included 48 patients. After 2h of treatment with
      heliox, the oxygen saturation and PaO2 significantly improved when compared with
      the air-oxygen group, 98.3% vs. 92.9%, 62.0mmHg vs. 43.6mmHg (p=0.04 and 0.01),
      respectively. Furthermore, PaO2/FiO2 ratio was significantly higher in the heliox
      group when compared with the air-oxygen group, 206.7 vs. 145.3. Nevertheless, CO2
      showed better elimination when heliox was used, without significance. MWCA score
      dropped significantly in the heliox group, 2.2 points vs. 4.0 points in air
      oxygen (p=0.04), 2h after starting the therapy. CONCLUSION: Transient improvement
      of oxygenation in infants with RSV acute bronchiolitis during the initial phase
      of the therapy is associated with heliox when provided with HFNC, may provide a
      precious time for other therapeutic agents to work or for the disease to resolve
      naturally, avoiding other aggressive interventions.

PMID- 28506665
TI  - Motor development of preterm infants assessed by the Alberta Infant Motor Scale:
      systematic review article.
AB  - OBJECTIVE: Premature newborns are considered at risk for motor development
      deficits, leading to the need for monitoring in early life. The aim of this study
      was to systematically review the literature about gross motor development of
      preterm infants, assessed by the Alberta Infant Motor Scale (AIMS) to identify
      the main outcomes in development. DATA SOURCE: Systematic review of studies
      published from 2006 to 2015, indexed in Pubmed, Scielo, Lilacs, and Medline
      databases in English and Portuguese. The search strategy included the keywords:
      Alberta Infant Motor Scale, prematurity, preterm, motor development, postural
      control, and follow-up. DATA SUMMARY: A total of 101 articles were identified and
      23 were selected, according to the inclusion criteria. The ages of the children
      assessed in the studies varied, including the first 6 months up to 15 or 18
      months of corrected age. The percentage variation in motor delay was identified
      in the motor outcome descriptions of ten studies, ranging from 4% to 53%,
      depending on the age when the infant was assessed. The studies show significant
      differences in the motor development of preterm and full-term infants, with a
      description of lower gross scores in the AIMS results of preterm infants.
      CONCLUSIONS: It is essential that the follow-up services of at-risk infants have
      assessment strategies and monitoring of gross motor development of preterm
      infants; AIMS is an assessment tool indicated to identify atypical motor
      development in this population.

PMID- 28506666
TI  - Prevalence and factors associated with body mass index in children aged 9-11
      years.
AB  - OBJECTIVE: This study aimed to identify the prevalence and factors associated
      with body mass index (BMI) in children aged 9-11 years. METHODS: The study is
      part of the International Study of Childhood Obesity Lifestyle and the
      Environment (ISCOLE). Body composition was determined using the bipolar
      bioimpedance technique. The mean BMI value was categorized as recommended by the
      World Health Organization. For seven consecutive days, participants used an
      accelerometer to objectively monitor sedentary behavior (SB) and moderate to
      vigorous physical activity. Individual factors (anthropometric and behavioral),
      family aspects, and family and school environment were provided by participants
      and parents and were analyzed by multilevel linear regression adjusted for
      gender, ethnicity, school, number of siblings, and total annual family income.
      RESULTS: The mean BMI was 20.1kg/m2, and 51.8% of the children were
      overweight/obese (50.3% boys, 53.4% girls, p=0.014). Considering all
      participants, the associated factors of BMI were body fat percentage (BF%,
      beta=0.0216, p<0.001) and screen time (ST, beta=0.0050, p=0.006). In boys, the
      associated factors were BF% (beta=0.0209, p<0.001), ST (beta=0.006, p=0.036), and
      healthy eating policies or practices (beta=0.0276, p=0.025). In girls, only BF%
      was associated (beta=0.0221, p<0.001) with BMI. CONCLUSIONS: High prevalence of
      overweight/obesity was observed in children from Sao Caetano do Sul. Different
      associated factors were identified between the genders, with only BF% being
      common in both genders.

PMID- 28506667
TI  - Is There an Upper Limit to Genome Size?
AB  - At 50-fold the size of the human genome (3 Gb), the staggeringly huge genome of
      147.3 Gb recently discovered in the fern Tmesipteris obliqua is comparable in
      size to those of the other plant and animal record-holders (i.e., Paris japonica,
      a flowering plant with a genome size of 148.8 Gb, and Protopterus aethiopicus, a
      lungfish with a genome of 130 Gb). The synthesis of available information on
      giant genomes suggests that the biological limit to genome size expansion in
      eukaryotes may have been reached. We propose several explanations for why the
      genomes of ferns, flowering plants, and lungfish, all of which have independently
      undergone dramatic increases in genome size through a variety of mechanisms, do
      not exceed 150 Gb.

PMID- 28506668
TI  - Characterization of selected municipal solid waste components to estimate their
      biodegradability.
AB  - Biological treatments of Residual Municipal Solid Waste (RMSW) allow to divert
      biodegradable materials from landfilling and recover valuable alternative
      resources. The biodegradability of the waste components needs however to be
      assessed in order to design the bioprocesses properly. The present study
      investigated complementary approaches to aerobic and anaerobic biotests for a
      more rapid evaluation. A representative sample of residual MSW was collected from
      a Mechanical Biological Treatment (MBT) plant and sorted out into 13 fractions
      according to the French standard procedure MODECOMTM. The different fractions
      were analyzed for organic matter content, leaching behavior, contents in
      biochemical constituents (determined by Van Soest's acid detergent fiber method),
      Biochemical Oxygen Demand (BOD) and Bio-Methane Potential (BMP). Experimental
      data were statistically treated by Principal Components Analysis (PCA).
      Cumulative oxygen consumption from BOD tests and cumulative methane production
      from BMP tests were found to be positively correlated in all waste fractions. No
      correlation was observed between the results from BOD or BMP bioassays and the
      contents in cellulose-like, hemicelluloses-like or labile organic compounds. No
      correlation was observed either with the results from leaching tests (Soluble
      COD). The contents in lignin-like compounds, evaluated as the non-extracted RES
      fraction in Van Soest's method, was found however to impact negatively the
      biodegradability assessed by BOD or BMP tests. Since cellulose, hemicelluloses
      and lignin are the polymers responsible for the structuration of lignocellulosic
      complexes, it was concluded that the structural organization of the organic
      matter in the different waste fractions was more determinant on biodegradability
      than the respective contents in individual biopolymers.

PMID- 28506669
TI  - Recycling and characterization of carbon fibers from carbon fiber reinforced
      epoxy matrix composites by a novel super-heated-steam method.
AB  - In order to manufacture high quality recycled carbon fibers (R-CFs), carbon fiber
      reinforced composite wastes were pyrolysed with super-heated steam at 550 
      degrees C in a fixed bed reactor for varying reaction times. The mechanical and
      surface properties of the R-CFs were characterized with a single fiber tensile
      test, interface shear strength (IFSS), scanning electron microscopy (SEM), and X
      ray photoelectron spectroscopy (XPS). The surface analysis showed that there was
      no matrix char residue on the fiber surfaces. The tensile strength and IFSS
      values of the R-CFs were 90% and 115% compared to those of virgin carbon fibers
      (V-CFs), respectively. The recycling efficiency of the R-CFs from the composites
      were strongly dependent on the pyrolysis temperature, reaction time, and super
      heated steam feeding rate.

PMID- 28506670
TI  - Effect of simulated mechanical recycling processes on the structure and
      properties of poly(lactic acid).
AB  - The aim of this work is to study the effects of different simulated mechanical
      recycling processes on the structure and properties of PLA. A commercial grade of
      PLA was melt compounded and compression molded, then subjected to two different
      recycling processes. The first recycling process consisted of an accelerated
      ageing and a second melt processing step, while the other recycling process
      included an accelerated ageing, a demanding washing process and a second melt
      processing step. The intrinsic viscosity measurements indicate that both
      recycling processes produce a degradation in PLA, which is more pronounced in the
      sample subjected to the washing process. DSC results suggest an increase in the
      mobility of the polymer chains in the recycled materials; however the degree of
      crystallinity of PLA seems unchanged. The optical, mechanical and gas barrier
      properties of PLA do not seem to be largely affected by the degradation suffered
      during the different recycling processes. These results suggest that, despite the
      degradation of PLA, the impact of the different simulated mechanical recycling
      processes on the final properties is limited. Thus, the potential use of recycled
      PLA in packaging applications is not jeopardized.

PMID- 28506671
TI  - Modeling of flux, binding and substitution of urea molecules in the urea
      transporter dvUT.
AB  - Urea transporters (UTs) are transmembrane proteins that transport urea molecules
      across cell membranes and play a crucial role in urea excretion and water
      balance. Modeling the functional characteristics of UTs helps us understand how
      their structures accomplish the functions at the atomic level, and facilitates
      future therapeutic design targeting the UTs. This study was based on the crystal
      structure of Desulfovibrio vulgaris urea transporter (dvUT). To model the binding
      behavior of urea molecules in dvUT, we constructed a cooperative binding model.
      To model the substitution of urea by the urea analogue N,N'-dimethylurea (DMU) in
      dvUT, we calculated the occupation probability of DMU along the urea pore and the
      ratio of the occupation probabilities of DMU at the external (Sext) and internal
      (Sint) binding sites, and we established the mutual substitution rule for binding
      and substitution of urea and DMU. Based on these calculations and modelings,
      together with the use of the Monte Carlo (MC) method, we further modeled the urea
      flux in dvUT, equilibrium urea binding to dvUT, and the substitution of urea by
      DMU in the dvUT. Our modeling results are in good agreement with the existing
      experimental functional data. Furthermore, the modelings have discovered the
      microscopic process and mechanisms of those functional characteristics. The
      methods and the results would help our future understanding of the underlying
      mechanisms of the diseases associated with impaired UT functions and rational
      drug design for the treatment of these diseases.

PMID- 28506672
TI  - Comparison of the Nosocomial Pneumonia Mortality Prediction (NPMP) model with
      standard mortality prediction tools.
AB  - BACKGROUND: Severity or mortality prediction of nosocomial pneumonia could aid in
      the effective triage of patients and assisting physicians. AIM: To compare
      various severity assessment scoring systems for predicting intensive care unit
      (ICU) mortality in nosocomial pneumonia patients. METHODS: A prospective cohort
      study was conducted in a tertiary care university-affiliated hospital in Manipal,
      India. One hundred patients with nosocomial pneumonia, admitted in the ICUs who
      developed pneumonia after >48h of admission, were included. The Nosocomial
      Pneumonia Mortality Prediction (NPMP) model, developed in our hospital, was
      compared with Acute Physiology and Chronic Health Evaluation II (APACHE II),
      Mortality Probability Model II (MPM72 II), Simplified Acute Physiology Score II
      (SAPS II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure
      Assessment (SOFA), Clinical Pulmonary Infection Score (CPIS), Ventilator
      Associated Pneumonia Predisposition, Insult, Response, Organ dysfunction (VAP
      PIRO). Data and clinical variables were collected on the day of pneumonia
      diagnosis. The outcome for the study was ICU mortality. The sensitivity and
      specificity of the various scoring systems was analysed by plotting receiver
      operating characteristic (ROC) curves and computing the area under the curve for
      each of the mortality predicting tools. FINDINGS: NPMP, APACHE II, SAPS II, MPM72
      II, SOFA, and VAP-PIRO were found to have similar and acceptable discrimination
      power as assessed by the area under the ROC curve. The AUC values for the above
      scores ranged from 0.735 to 0.762. CPIS and MODS showed least discrimination.
      CONCLUSION: NPMP is a specific tool to predict mortality in nosocomial pneumonia
      and is comparable to other standard scores.

PMID- 28506673
TI  - High frequency of silver resistance genes in invasive isolates of Enterobacter
      and Klebsiella species.
AB  - BACKGROUND: Silver-based products have been marketed as an alternative to
      antibiotics, and their consumption has increased. Bacteria may, however, develop
      resistance to silver. AIM: To study the presence of genes encoding silver
      resistance (silE, silP, silS) over time in three clinically important
      Enterobacteriaceae genera. METHODS: Using polymerase chain reaction (PCR), 752
      bloodstream isolates from the years 1990-2010 were investigated. Age, gender, and
      ward of patients were registered, and the susceptibility to antibiotics and
      silver nitrate was tested. Clonality and single nucleotide polymorphism were
      assessed with repetitive element sequence-based PCR, multi-locus sequence typing,
      and whole-genome sequencing. FINDINGS: Genes encoding silver resistance were
      detected most frequently in Enterobacter spp. (48%), followed by Klebsiella spp.
      (41%) and Escherichia coli 4%. Phenotypical resistance to silver nitrate was
      found in Enterobacter (13%) and Klebsiella (3%) isolates. The lowest carriage
      rate of sil genes was observed in blood isolates from the neonatology ward (24%),
      and the highest in blood isolates from the oncology/haematology wards (66%).
      Presence of sil genes was observed in international high-risk clones. Sequences
      of the sil and pco clusters indicated that a single mutational event in the silS
      gene could have caused the phenotypic resistance. CONCLUSION: Despite a
      restricted consumption of silver-based products in Swedish health care, silver
      resistance genes are widely represented in clinical isolates of Enterobacter and
      Klebsiella species. To avoid further selection and spread of silver-resistant
      bacteria with a high potential for healthcare-associated infections, the use of
      silver-based products needs to be controlled and the silver resistance monitored.

PMID- 28506674
TI  - Removal of an Infected Hip Arthroplasty Is a High-Risk Surgery: Putting Morbidity
      Into Context With Other Major Nonorthopedic Operations.
AB  - BACKGROUND: Two-stage revision remains the most common approach to periprosthetic
      joint infection of total hip arthroplasty (THA) in the United States. The
      postoperative risks associated with removal of an infected prosthesis and
      placement of a spacer have not been thoroughly studied. METHODS: Patients who
      underwent THA implant removal and spacer placement for infection were identified
      in a large administrative database. Morbidity and mortality rates were assessed
      for the 90-day postoperative period and readmission rates were assessed at 30
      days postoperatively. These outcomes were then compared with those after coronary
      artery bypass grafting, carotid endarterectomy, prostatectomy,
      pancreatoduodenectomy (Whipple procedure), and kidney transplant. RESULTS:
      Implant removal and spacer placement for THA periprosthetic joint infection (n =
      10,386) had a 30-day readmission rate of 11.1% and 90-day mortality rate of 2.6%.
      Major complications were seen in 15.3% patients. Postoperative morbidity was
      often higher in these patients when compared with other procedures studied.
      Ninety-day mortality rates were significantly higher compared with carotid
      endarterectomy, prostatectomy, and kidney transplant (odds ratio [ORs] between
      2.1 and 12.5; P < .0001). Readmission rates at 30 days were significantly higher
      than all other groups including coronary artery bypass grafting and Whipple (ORs
      between 1.4 and 8.2; P < .0001). CONCLUSION: Removal of an infected THA with
      spacer placement is a high-risk surgery. This large study that includes over
      10,000 patients helps quantify the risks of readmission, morbidity, and
      mortality. The rates of adverse outcomes are higher than those for many
      nonorthopedic operations typically considered to be major surgery.

PMID- 28506675
TI  - Impact of Comorbidities on Outcome After Total Hip Arthroplasty.
AB  - BACKGROUND: Patient-reported outcome scores gain increasing importance in
      quantifying clinical success and procedure remuneration. Our aim was to evaluate
      the impact of comorbidity on joint-specific outcome and general health in
      patients undergoing elective total hip arthroplasty (THA). METHODS: Longitudinal
      data on THA procedures were used to evaluate the association between comorbidity
      and surgical outcome in terms of joint-specific measures and general health
      (Forgotten Joint Score-12 [FJS-12], Oxford Hip Score [OHS], and Short Form-12) at
      1-year follow-up. Comorbidities comprised the Charlson comorbidity index (CCI),
      low back pain (LBP), pain from other joints (POJ), and body mass index. RESULTS:
      We analyzed data from 251 THA patients (age: 67.7 +/- 11.8 years; 58.2% female).
      Most common conditions were POJ (75.9%), LBP (55.1%), connective tissue disease
      (12.1%), and diabetes (5.6%). With regard to postoperative improvement, we did
      not find statistically significant differences between patients with or without
      CCI comorbidities (FJS-12, +38.7 vs +43.2, P = .370; OHS, +15.6 vs +17.9, P =
      .100) or POJ (FJS-12, +39.9 vs +45.1, P = .325; OHS, +17.3 vs +16.6, P = .645).
      Patients with LBP showed less improvement on the FJS-12 than those without LBP
      (+35.6 vs +49.1; P = .002), whereas no difference was found for the OHS (+17.9 vs
      +16.5; P = .266). CONCLUSION: Patients with comorbid conditions report lower
      preoperative and postoperative outcome scores compared with patients with no such
      conditions; however, there was no statistically significant association of CCI
      comorbidities and POJ with postoperative improvement in joint-specific outcomes.
      LBP was found to have a negative impact on postoperative improvement in terms of
      joint awareness.

PMID- 28506677
TI  - Controller design for a class of nonlinear MIMO coupled system using multiple
      models and second level adaptation.
AB  - In this paper, an adaptive control method using multiple models with second level
      adaptation is proposed for a class of nonlinear multi-input multi-output (MIMO)
      coupled systems. Multiple estimation models are used to tune the unknown
      parameters at the first level. The second level adaptation provides a single
      parameter vector for the controller. A feedback linearization technique is used
      to design a state feedback control. The efficacy of the designed controller is
      validated by conducting real time experiment on a laboratory setup of twin rotor
      MIMO system (TRMS). The TRMS setup is discussed in detail and the experiments
      were performed for regulation and tracking problem for pitch and yaw control
      using different reference signals. An Extended Kalman Filter (EKF) has been used
      to observe the unavailable states of the TRMS.

PMID- 28506676
TI  - Bile acids and gestation.
AB  - There are numerous profound maternal physiological changes that occur from
      conception onwards and adapt throughout gestation in order to support a healthy
      pregnancy. By the time of late gestation, when circulating pregnancy hormones are
      at their highest concentrations, maternal adaptations include relative
      hyperlipidemia, hypercholanemia and insulin resistance. Bile acids have now been
      established as key regulators of metabolism, and their role in gestational
      changes in metabolism is becoming apparent. Bile acid homeostasis is tightly
      regulated by the nuclear receptor FXR, which has been shown to have reduced
      activity during pregnancy. This review focuses on the gestational alterations in
      bile acid homeostasis that occur in normal pregnancy, which in some women can
      become pathological, leading to the development of intrahepatic cholestasis of
      pregnancy. As well as their important role in maternal metabolic health, we will
      review bile acid metabolism in the feto-placental unit.

PMID- 28506678
TI  - Adaptive super-twisting sliding mode control for a three-phase single-stage grid
      connected differential boost inverter based photovoltaic system.
AB  - This paper presents an adaptive super-twisting sliding mode control (STC) along
      with double-loop control for voltage tracking performance of three-phase
      differential boost inverter and DC-link capacitor voltage regulation in grid
      connected PV system. The effectiveness of the proposed control strategies are
      demonstrated under realistic scenarios such as variations in solar insolation,
      load power demand, grid voltage, and transition from grid-connected to standalone
      mode etc. Additional supplementary power quality control functions such as
      harmonic compensation, and reactive power management are also investigated with
      the proposed control strategy. The results are compared with conventional
      proportional-integral controller, and PWM sliding mode controller. The system
      performance is evaluated in simulation and in real-time.

PMID- 28506679
TI  - Scoping Review of the Mental Health of Parents of Infants in the NICU.
AB  - OBJECTIVE: To synthesize and summarize evidence regarding the mental health of
      parents of infants in the NICU. DATA SOURCES: Thirteen electronic databases were
      searched in October 2014 using the following terms individually and in
      combination: postpartum woman, mother, NICU, preterm birth, depression, anxiety,
      acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and parental
      stress. STUDY SELECTION: We examined the published research regarding the
      experiences of parents who have infants admitted to the NICU, the mental health
      problems that parents may develop, the tools that have been used to identify such
      problems, and factors related to parental mental health. DATA EXTRACTION: After
      the exclusion of articles according to preset criteria, we included 66 articles
      in the full review. DATA SYNTHESIS: Mental health issues are common in parents of
      infants in the NICU across diverse ethnocultural groups and countries. Parents
      report feelings of guilt and shame, high levels of stress, mood and anxiety
      symptoms, and the positive influence of specific coping strategies and social
      support. The ethnocultural meanings of these experience and thus nursing
      interventions may differ widely. CONCLUSION: Ongoing assessments of the mental
      health of parents should be part of routine NICU care. Identification of mood and
      anxiety symptoms and testing innovative interventions to address at-risk or
      affected parents is imperative to ensure that there are culturally appropriate
      policies and services in place to respond to the mental health needs of NICU
      families.

PMID- 28506681
TI  - Evaluation of carotid intima-media thickness with vascular endothelial growth
      factor and malondialdehyde levels in patients with sarcoidosis.
AB  - PURPOSE: To assess the impact of sarcoidosis on endothelial function by measuring
      carotid intima-media thickness (CIMT) and serum levels of malondialdehyde and
      vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: We
      prospectively analyzed 41 patients with sarcoidosis (9 men, 32 women) with a mean
      age of 44.9+/-10.2 (SD) years and 34 healthy subjects (9 men, 24 women) with a
      mean age of 37.26+/-8.9 (SD) years who served as a control group. Sarcoidosis
      patients receiving steroids were included in Group 1 while those not under
      steroid treatment were included in Group 2. CIMT measurements were performed
      using B-mode ultrasound. Malondialdehyde and VEGF serum levels were obtained in
      all sarcoidosis patients and control subjects. RESULTS: Both right and left CIMT
      was significantly higher in Group 1 and Group 2 than in control subjects. Serum
      levels of malondialdehyde and VEGF in Group 1 and Group 2 were significantly
      higher than in healthy subjects. No differences in CIMT, malondialdehyde and VEGF
      were found between Group 1 and Group 2. CONCLUSION: Sarcoidosis results in
      increased CIMT, VEGF and malondialdehyde serum levels. However, there was no
      difference in terms of CIMT, VEGF and malondialdehyde levels between sarcoidosis
      patients with or without steroid treatment, suggesting that new treatment
      strategies for sarcoidosis vascular involvement should consider this result.

PMID- 28506680
TI  - Expanding role of percutaneous cholecystostomy and interventional radiology for
      the management of acute cholecystitis: An analysis of 144 patients.
AB  - PURPOSE: To investigate the rates of interval cholecystectomy and recurrent
      cholecystitis after initial percutaneous cholecystostomy (PC) and identify
      predictors of patient outcome after PC. MATERIALS AND METHODS: A total of 144
      patients with acute cholecystitis who were treated with PC were included. There
      were 96 men and 48 women, with a mean age of 71+/-13 (SD) years (range: 25-100
      years). Patient characteristics, diagnostic imaging studies and results of
      laboratory tests at initial presentation, clinical outcomes after the initial PC
      treatment were reviewed. RESULTS: Among the 144 patients, 56 patients were
      referred for acute acalculous and 88 patients for calculus cholecystitis. Five
      procedure-related major complications (3.6%) were observed including bile
      peritonitis (n=3), hematoma (n=1) and abscess formation (n=1). Recurrent acute
      cholecystitis after initial clinical resolution and PC tube removal was observed
      in 8 patients (6.0%). The rate of interval cholecystectomy was 33.6% (47/140)
      with an average interval period of 100+/-482 (SD) days (range: 3-1017 days). PC
      was a definitive treatment in 85 patients (60.7%) whereas 39 patients (27.9%) had
      elective interval cholecystectomy without having recurrent cholecystitis. The
      clinical outcomes after PC did not significantly differ between patients with
      calculous cholecystitis and those with acalculous cholecystitis. Multiple prior
      abdominal operations were associated with higher rates of recurrent
      cholecystitis. CONCLUSION: For both acute acalculous and calculous cholecystitis,
      PC is an effective and definitive treatment modality for more than two thirds of
      our study patients over 3.5-year study period with low rates of recurrent disease
      and interval cholecystectomy.

PMID- 28506682
TI  - Colorectal cancer-inflammatory bowel disease nexus and felony of Escherichia
      coli.
AB  - Colorectal cancer (CRC) has a multifactorial etiology. Although the exact cause
      of CRC is still elusive, recent studies have indicated microbial involvement in
      its etiology. Escherichia coli has emerged as an important factor in CRC
      development since the bacterium can cause changes in the gut that lead to
      cancerous transformation. A number of studies indicate that chronic inflammation
      induced by microorganisms, including E. coli, during inflammatory bowel disease
      (IBD) predisposes an individual to CRC. The evidence that support the role of E.
      coli in the etiology of CRC, through IBD, is not limited only to chronic
      inflammation. The growth of E. coli as an intracellular pathogen during IBD and
      CRC enable the bacteria to modulate the host cell cycle, induce DNA damage and
      accumulate mutations. These are some of the contributing factors behind the
      etiology of CRC. The present article considers the current status of the
      involvement of E. coli, through IBD, in the etiology of CRC. We discuss how
      intracellular E. coli infection can cause changes in the gut that can eventually
      lead to cellular transformation. In addition, the recent management strategies
      that target E. coli for prevention of CRC are also discussed.

PMID- 28506683
TI  - The caspase-1 inhibitor CARD18 is specifically expressed during late
      differentiation of keratinocytes and its expression is lost in lichen planus.
AB  - BACKGROUND: CARD18 contains a caspase recruitment domain (CARD) via which it
      binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro
      inflammatory cytokine interleukin (IL)-1beta. OBJECTIVES: To determine the
      expression profile and the role of CARD18 during differentiation of keratinocytes
      and to compare the expression of CARD18 in normal skin and in inflammatory skin
      diseases. METHODS: Human keratinocytes were induced to differentiate in monolayer
      and in 3D skin equivalent cultures. In some experiments, CARD18-specific siRNAs
      were used to knock down expression of CARD18. CARD18 mRNA levels were determined
      by quantitative real-time PCR, and CARD18 protein was detected by Western blot
      and immunofluorescence analyses. In situ expression was analyzed in skin biopsies
      obtained from healthy donors and patients with psoriasis and lichen planus.
      RESULTS: CARD18 mRNA was expressed in the epidermis at more than 100-fold higher
      levels than in any other human tissue. Within the epidermis, CARD18 was
      specifically expressed in the granular layer. In vitro CARD18 was strongly
      upregulated at both mRNA and protein levels in keratinocytes undergoing terminal
      differentiation. In skin equivalent cultures the expression of CARD18 was
      efficiently suppressed by siRNAs without impairing stratum corneum formation.
      Epidermal expression of CARD18 was increased after ultraviolet (UV)B irradiation
      of skin explants. In skin biopsies of patients with psoriasis no consistent
      regulation of CARD18 expression was observed, however, in lesional epidermis of
      patients with lichen planus, CARD18 expression was either greatly diminished or
      entirely absent whereas in non-lesional areas expression was comparable to normal
      skin. CONCLUSIONS: Our results identify CARD18 as a differentiation-associated
      keratinocyte protein that is altered in abundance by UV stress. Its
      downregulation in lichen planus indicates a potential role in inflammatory
      reactions of the epidermis in this disease.

PMID- 28506684
TI  - Study of Preanalytic and Analytic Variables for Clinical Next-Generation
      Sequencing of Circulating Cell-Free Nucleic Acid.
AB  - Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next
      generation sequencing (NGS) has opened up new possibilities for monitoring
      treatment response and disease progression in patients with solid tumors.
      However, implementation of cfDNA genotyping in diagnostic laboratories requires
      systematic assessment of preanalytical parameters and analytical performance of
      NGS platforms. We assessed the effects of peripheral blood collection tube and
      plasma separation time on cfDNA yield and integrity and performance of the Ion
      PGM, Proton, and MiSeq NGS platforms. cfDNA from 31 patients with diverse
      advanced cancers and known tumor mutation status was deep sequenced using
      targeted hotspot panels. Forty-five of 52 expected mutations and two additional
      mutations (KRAS p.Q61H and EZH2 p.Y646F) were detected in plasma through a custom
      bioinformatics pipeline. We observed comparable cfDNA concentration/integrity
      between collection tubes within 16 hours of plasma separation and equal
      analytical performance among NGS platforms, with 1% detection sensitivity for
      cfDNA genotyping.

PMID- 28506685
TI  - Simultaneous Genotyping of alpha-Thalassemia Deletional and Nondeletional
      Mutations by Real-Time PCR-Based Multicolor Melting Curve Analysis.
AB  - alpha-Thalassemia, which is caused by defective synthesis of the hemoglobin alpha
      globin chains, is the most commonly inherited recessive hemoglobin abnormality.
      Genetic detection of a defective alpha-globin gene is challenging because of a
      variety of large deletions of the alpha-globin gene cluster and nondeletional
      mutations. Separate detections of them are often required using complex and error
      prone open-tube methods. We report a novel real-time PCR-based assay that can
      simultaneously genotype four major deletional and three common nondeletional
      mutations in two parallel reactions by using multicolor melting curve analysis.
      The turnaround time of this closed-tube assay was within 3.5 hours, the limit of
      detection was 5 ng of human genomic DNA per reaction, and as low as 5% mutant DNA
      could be detected in the mosaic samples. The assay was evaluated using 1213
      precharacterized genomic DNA samples in a double-blind manner. All seven alpha
      thalassemia mutations were accurately genotyped, yielding a 99.3% concordance
      with the comparison assays. The 14 discordant samples contained the HKalphaalpha
      allele that was undetected by the traditional methods. Considering its rapidity,
      ease of use, and accuracy, we concluded that our real-time PCR assay may be
      recommended as an alternative screening and diagnostic tool for alpha
      thalassemia.

PMID- 28506686
TI  - Excessively delayed maternal reaction after their perception of decreased fetal
      movements in stillbirths: Population-based study in Japan.
AB  - BACKGROUND: Fetal movement is the most common method to evaluate fetal well
      being. Furthermore, maternal perception of decreased fetal movements is
      associated with perinatal demise. Previously, we showed that perception of
      decreased fetal movements was the most common reason for mothers visiting the
      outpatient department among those who had stillbirths in our region. Further
      investigation of stillbirths with decreased fetal movements is essential to find
      a possible way of preventing stillbirth. AIM: To investigate maternal reaction
      time after their perceiving decreased fetal movements among stillbirths in our
      region of Japan. METHODS: This is a population-based study of stillbirths in
      Shiga Prefecture, Japan conducted from 2007 to 2011. We sent a questionnaire to
      each obstetrician who had submitted the stillbirth certificate. We reviewed and
      evaluated the questionnaires returned from the obstetricians. FINDINGS: There
      were 66 cases (35%) with decreased fetal movements among 188 stillbirths in Shiga
      during the study period. The number of maternal visits to outpatient department
      after perception of decreased fetal movements within 24h was only seven (11%)
      among 64 stillbirths diagnosed at outpatient department. CONCLUSION: We conclude
      that delayed maternal visit after perceiving decreased fetal movements is
      frequently observed in stillbirths. Promoting more thorough maternal education on
      fetal movements, including emphasizing earlier visitation after perceiving
      decreased fetal movements, may prevent stillbirths.

PMID- 28506687
TI  - Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) related
      lymphomas, pathology view point.
AB  - The contribution of Epstein Barr virus (EBV) and Kaposi sarcoma herpes virus
      (KSHV) to the development of specific types of malignant lymphomas occurring in
      the human immunodeficiency virus (HIV) setting has been extensively studied since
      the beginning of the HIV epidemic 35 years ago. The introduction of highly active
      antiretroviral therapies (HAART) in 1996 has changed dramatically the incidence
      of HIV-related malignancies. Nevertheless, malignant lymphomas continue to be the
      major group of malignances observed in HIV infected individuals, and the most
      common cause of cancer related-deaths. Common features of the predominant B-cell
      lymphomas in the HIV+ setting are the frequent plasmacytoid morphology of the
      neoplastic cells, advanced stage, aggressive disease and frequent extranodal
      involvement. In this article, we review the evolving concepts and definitions of
      the various EBV-associated lymphomas in HIV+ patients, including diffuse large B
      cell lymphoma, Burkitt lymphoma, classical Hodgkin lymphoma, plasmablastic
      lymphoma and primary effusion lymphoma. The current knowledge regarding the
      pathogenesis of these malignancies, the interplay between HIV and EBV co
      infection in the development of certain HIV related lymphomas, and the emerging
      paradigm that suggests that HIV may play a direct role in lymphomagenesis are
      explored as well.

PMID- 28506688
TI  - Human immunodeficiency virus and fungal infections.
AB  - The discovery of HIV was largely due to the presence of Pneumocystis pneumonia
      (PCP) in young patients that did not have the usual known causes of immune
      deficiencies in the early 1980s. Currently, treatment with highly active anti
      retroviral therapy (HAART) and the use of prophylaxis for PCP have lowered the
      frequency of fungal infections; however, these infections continue to cause
      morbidity and mortality in those patients that fall out or are not in care. The
      frequency of specific fungal diseases in HIV patients will depend on the
      prevalence of fungi in the particular geographic location. Nowadays, superficial
      and invasive Candida infections, PCP, and cryptococci are the most frequent
      fungal infections seen in HIV positive patients worldwide. The role of pathology
      in diagnosing fungal infections is crucial because a lesion may be biopsied
      without obtaining mycology cultures, certain organisms may take several weeks to
      grow, or the sample sent to the mycology laboratory may not have the organism.
      Following we will describe fungal infections that are particularly frequent in
      HIV infected patients and their key pathological features.

PMID- 28506690
TI  - Romidepsin induces caspase-dependent cell death in human neuroblastoma cells.
AB  - Neuroblastoma is the most common extracranial pediatric solid tumor, arising from
      the embryonic sympathoadrenal lineage of the neural crest, and is responsible for
      15% of childhood cancer deaths. Although survival rates are good for some
      patients, those children diagnosed with high-risk neuroblastoma have survival
      rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge
      and the development of novel therapeutic strategies is essential. Given that
      there is widespread epigenetic dysregulation in neuroblastoma, epigenetic
      pharmacotherapy holds promise as a therapeutic approach. In recent years, histone
      deacetylase (HDAC) inhibitors, which cause selective activation of gene
      expression, have been shown to be potent chemotherapeutics for the treatment of a
      wide range of cancers. Here we examined the ability of the FDA-approved drug
      Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in
      neuroblastoma cells. Treatment with Romidepsin at concentrations in the low
      nanomolar range induced neuroblastoma cell death through caspase-dependent
      apoptosis. Romidepsin significantly increased histone acetylation, and
      significantly enhanced the cytotoxic effects of the cytotoxic agent 6
      hydroxydopamine, which has been shown to induce cell death in neuroblastoma cells
      through increasing reactive oxygen species. Romidepsin was also more potent in
      MYCN-amplified neuroblastoma cells, which is an important prognostic marker of
      poor survival. This study has thus demonstrated that the FDA-approved
      chemotherapeutic drug Romidepsin has a potent caspase-dependent cytotoxic effect
      on neuroblastoma cells, whose effects enhance cell death induced by other
      cytotoxins, and suggests that Romidepsin may be a promising chemotherapeutic
      candidate for the treatment of neuroblastoma.

PMID- 28506689
TI  - Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel
      Disease in Humans and Mice.
AB  - BACKGROUND & AIMS: The role of tobacco smoke in the etiology of inflammatory
      bowel disease (IBD) is unclear. We investigated interactions between genes and
      smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and
      ulcerative colitis (UC) in a case-only study of patients and in mouse models of
      IBD. METHODS: We used 55 Immunochip-wide datasets that included 19,735 IBD cases
      (10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta
      analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never
      vs ever smokers, never vs current smokers, and never vs former smokers. We
      studied the effects of exposure to cigarette smoke in Il10-/- and Nod2-/- mice,
      as well as in Balb/c mice without disruption of these genes (wild-type mice).
      Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8
      weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines
      were collected and analyzed histologically and by reverse transcription
      polymerase chain reaction. RESULTS: We identified 64 single nucleotide
      polymorphisms (SNPs) for which the association between the SNP and IBD were
      modified by smoking behavior (meta-analysis Wald test P < 5.0 * 10-5;
      heterogeneity Cochrane Q test P > .05). Twenty of these variants were located
      within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from
      SNP genotypes) revealed an interaction with smoking. We replicated the
      interaction of a variant in NOD2 with current smoking in relation to the risk for
      CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the
      same genomic region (rs2270368 and rs17221417) that interact with smoking in
      relation to CD risk. Approximately 45% of the SNPs that interact with smoking
      were in close vicinity (<=1 Mb) to SNPs previously associated with IBD; many were
      located near or within genes that regulate mucosal barrier function and immune
      tolerance. Smoking modified the disease risk of some variants in opposite
      directions for CD vs UC. Exposure of Interleukin 10 (il10)-deficient mice to
      cigarette smoke accelerated development of colitis and increased expression of
      interferon gamma in the small intestine compared to wild-type mice exposed to
      smoke. NOD2-deficient mice exposed to cigarette smoke developed ileitis,
      characterized by increased expression of interferon gamma, compared to wild-type
      mice exposed to smoke. CONCLUSIONS: In an analysis of 55 Immunochip-wide
      datasets, we identified 64 SNPs whose association with risk for IBD is modified
      by tobacco smoking. Gene-smoking interactions were confirmed in mice with
      disruption of Il10 and Nod2-variants of these genes have been associated with
      risk for IBD. Our findings from mice and humans revealed that the effects of
      smoking on risk for IBD depend on genetic variants.

PMID- 28506692
TI  - Sex differences in microglial appetites during development: Inferences and
      implications.

PMID- 28506691
TI  - Urinary lysophopholipids are increased in diabetic patients with nephropathy.
AB  - Diabetic nephropathy (DN) is a major cause of chronic kidney disease that
      frequently leads to end stage renal failure. Lysophosphatidic acid (LPA) and
      lysophosphatidylcholine (LPC) are lysophospholipid mediators shown to accumulate
      in kidney and to promote renal inflammation and tubulo-interstitial fibrosis in
      diabetic rodent models. Here we assessed whether LPA and LPC were associated to
      the development of nephropathy in diabetic human patients. Several molecular
      species of LPA and LPC were quantified by LC/MS-MS in urine and plasma from type
      2 diabetic patients with (cases; n=41) or without (controls, n=41) nephropathy
      symptoms (micro/macro-albuminuria and eGFR<60ml/min/1.73m2). Cases and controls
      were matched for sex, age and diabetes duration. Six species were detected in
      urine for both LPA and LPC, LPA16:0, LPA20:4, LPC16:0, LPC18:0, LPC18:1, and
      LPC18:2 that were significantly more concentrated in cases than in controls.
      Total LPC and LPA (sum of detected species) were significantly and exclusively
      associated with albuminuria (P<0.0001 and P=0.0009 respectively) and were
      significantly higher in the 3rd when compared to the 1st albuminuria tertile in
      cases. Plasma lysophospholipids showed a different species profile urine and
      their concentrations were not different between cases and controls. In
      conclusion, urine concentration of lysophospholipids increases in diabetic
      patients with DN as the likely result of their co-excretion with albumin combined
      with possible local production by kidney. Because LPA and LPC are known to
      promote renal inflammation and tubulo-interstitial fibrosis, their increased
      production in DN could participate to the development of kidney damage associated
      with diabetes.

PMID- 28506693
TI  - Survival prediction of non-small cell lung cancer patients using radiomics
      analyses of cone-beam CT images.
AB  - BACKGROUND AND PURPOSE: In this study we investigated the interchangeability of
      planning CT and cone-beam CT (CBCT) extracted radiomic features. Furthermore, a
      previously described CT based prognostic radiomic signature for non-small cell
      lung cancer (NSCLC) patients using CBCT based features was validated. MATERIAL
      AND METHODS: One training dataset of 132 and two validation datasets of 62 and
      94stage I-IV NSCLC patients were included. Interchangeability was assessed by
      performing a linear regression on CT and CBCT extracted features. A two-step
      correction was applied prior to model validation of a previously published
      radiomic signature. Results 13.3% (149 out of 1119) of the radiomic features,
      including all features of the previously published radiomic signature, showed an
      R2 above 0.85 between intermodal imaging techniques. For the radiomic signature,
      Kaplan-Meier curves were significantly different between groups with high and low
      prognostic value for both modalities. Harrell's concordance index was 0.69 for CT
      and 0.66 for CBCT models for dataset 1. Conclusions The results show that a
      subset of radiomic features extracted from CT and CBCT images are interchangeable
      using simple linear regression. Moreover, a previously developed radiomics
      signature has prognostic value for overall survival in three CBCT cohorts,
      showing the potential of CBCT radiomics to be used as prognostic imaging
      biomarker.

PMID- 28506694
TI  - Optogenetics gets to the heart: A guiding light beyond defibrillation.
AB  - Optogenetics provides a tool for controlling the electrical activity of excitable
      cells by means of the interaction of light with light-gated ion channels. Despite
      the fact that optogenetics has been intensively utilized in the neurosciences, it
      has been more rarely employed as an instrument for studying cardiac
      pathophysiology. However, the advantages of optical approaches to perturb cardiac
      electrical activity are numerous, especially when the spatio-temporal qualities
      of light are utterly exploited. Here, we review the main breakthroughs employing
      optogenetics to perturb cardiac pathophysiology and attempt a comparison of
      methods and procedures that have employed optogenetics in the heart. We
      particularly focus on light-based defibrillation strategies that represent one of
      the latest achievements in this field. We highlight the important role of
      advanced optical methods for detecting and stimulating electrical activity for
      optimizing defibrillation strategies and, more generally, for dissecting novel
      insights in cardiac physiology. Finally, we discuss the main future perspectives
      that we envision for optogenetics in the heart, both in terms of translational
      applications and for addressing fundamental questions of cardiac function.

PMID- 28506695
TI  - D816V mutation in the KIT gene activation loop has greater cell-proliferative and
      anti-apoptotic ability than N822K mutation in core-binding factor acute myeloid
      leukemia.
AB  - In core-binding factor acute myeloid leukemia (CBF-AML), there have been
      conflicting reports regarding the status as an unfavorable prognostic factor of
      mutation in the KIT gene, the significance of which remains unclear. We
      previously reported that prognoses differ between the KIT D816V and N822K
      mutations. In the present study, we compared in vitro the cell-proliferative and
      anti-apoptotic ability of D816V and N822K. We transduced these KIT mutations into
      the interleukin-3-dependent cell line TF-1 (TF-1 KITD816V, TF-1 KITN822K). When
      these KIT mutations were transduced into TF-1 cells, the cells acquired a
      proliferative ability independent of growth factor, which was significantly
      higher in TF-1 KITD816V than in TF-1 KITN822K (p = 0.022). When Ara-C was added
      in the absence of growth factor, Annexin V assay revealed that TF-1 KITD816V was
      associated with a significantly lower proportion of apoptotic cells than TF-1
      KITN822K (p < 0.001). Regarding signal transduction pathways, both KIT D816V and
      KIT N822K underwent autophosphorylation in the absence of growth factor. This was
      followed in KIT D816V by downstream activation of the SRC family kinase pathway
      in addition to the Janus kinase/signal transducers and activators of
      transcription (JAK/STAT) pathway, and in KIT N822K by downstream activation of
      the mitogen-activated protein kinase (MAPK) pathway in addition to the JAK/STAT
      pathway. These findings establish that D816V and N822K mutations are situated
      closely on the KIT receptor activation loop, but D816V has greater cell
      proliferative and anti-apoptotic ability than N822K.

PMID- 28506696
TI  - Current approaches for avoiding the limitations of circulating tumor cells
      detection methods-implications for diagnosis and treatment of patients with solid
      tumors.
AB  - Eight million people die of cancer each year and 90% of deaths are caused by
      systemic disease. Circulating tumor cells (CTCs) contribute to the formation of
      metastases and thus are the subject of extensive research and an abiding interest
      to biotechnology and pharmaceutical companies. Recent technological advances have
      resulted in greatly improved CTC detection, enumeration, expansion, and culture
      methods. However, despite the fact that nearly 150 years have passed since the
      first detection and description of CTCs in human blood and enormous technological
      progress that has taken place in this field, especially within the last decade,
      few CTC detection methods have been approved for routine clinical use. This
      reflects the substantial methodological problems related to the nature of these
      cells, their heterogeneity, and diverse metastatic potential. Here, we provide an
      overview of CTC phenotypes, including the plasticity of CTCs and the relevance of
      inflammation and cell fusion phenomena for CTC biology. We also review the
      literature on CTC detection methodology-its recent improvements, clinical
      significance, and efforts of its clinical application in cancer patients
      management. At present, CTC detection remains a challenging diagnostic approach
      as a result of numerous current methodological limitations. This is especially
      problematic during the early stages of the disease due to the small numbers of
      CTCs released into the blood of cancer patients. Nonetheless, the rapid
      development of novel techniques of CTC detection and enumeration in peripheral
      blood is expected to expedite their implementation in the clinical setting. It is
      of utmost importance to understand the biology of CTCs and their distinct
      populations as a prerequisite for achieving this ultimate goal.

PMID- 28506697
TI  - Inflammation and hemostasis in older octogenarians: implication in 5-year
      survival.
AB  - Social changes and medical advances have increased longevity, but the conditions
      governing healthy vs unhealthy cardiovascular (CV) aging are not fully known.
      Factors beyond classical CV risk factors may have an important unrecognized
      value. We sought to identify proteins differentially expressed in healthy
      octogenarians (HOs) without a history of cardiovascular disease (CVD) and
      preserved functional and cognitive state compared with octogenarians with a
      history of CVD and cognitive decline (UHOs) using a systems biology approach, and
      investigated how these proteins relate to CV mortality at 5-year follow-up.
      Plasmas obtained from older octogenarians (87 +/- 0 years) were analyzed by 2-DE
      + MS and bioinformatic pathway analysis in HOs (N = 38) and UHOs with cognitive
      (MEC<25) and functional (Barthel<90) decline and a previous ischemic event (acute
      myocardial infarction and/or stroke; N = 27). Results were validated by ELISA in
      HOs and UHOs and in an additional group of older octogenarians without cognitive
      impairment but with a previous CVD manifestation (HO-CVD; N = 35). UHOs showed a
      coordinated change in several inflammation-related proteins (AMBP, RBP4, and
      ITIH4; P < 0.05), together with a significant increase in the major inducer of
      the acute-phase reaction, interleukin-6 (P = 0.03). UHOs also showed a
      coordinated increase in hemostatic proteins that was associated with an
      impairment of fibrinolysis and an increased 5-year CV mortality (P = 0.003). The
      combination of inflammation (ITIH4 and interleukin-6) and hemostatic markers (D
      dimer, A2AP, and coagulation factor XIII) was able to discriminate the presence
      of an unhealthy phenotype in the elderly (AUC = 0.750; P = 0.001). Unhealthy
      older octogenarians show increased levels of several plasma proteins of
      inflammation and coagulation. In older octogenarians, the increase in hemostatic
      markers indicated an increase in 5-year CV mortality at follow-up.

PMID- 28506698
TI  - Antiproliferative and cytotoxic effects of green coffee and yerba mate extracts,
      their main hydroxycinnamic acids, methylxanthine and metabolites in different
      human cell lines.
AB  - : This work aimed at studying the effects of green coffee bean (GCBE) and yerba
      mate (YME) extracts, their main phenolic components (5-caffeoylquinic acid, 5
      CQA; 3,5-dicaffeoylquinic acid, 3,5-DCQA) and metabolites (ferulic acid, FA;
      caffeic acid, CA; dihydrocaffeic acid, DHCA; and dihydroferulic acid, DHFA) along
      with caffeine (CAF) on the viability and proliferation of different human cell
      lines. Extracts (10-1000 MUg/mL) and standards (10-1000 MUM) were assayed in
      colon (Caco-2), lung (A549), oesophageal (OE-33), urinary bladder (T24) human
      carcinoma cells, and a non-cancer cell line (CCD-18Co). YME significantly reduced
      viability of cancer cells at all assayed concentrations, the higher doses also
      reducing cell proliferation. GCBE effects on cell viability were more effective
      at 100 and 1000 MUg/mL, showing modest effects on cell proliferation. The highest
      doses of 5-CQA and 3,5-DCQA reduced cell viability and proliferation in all cell
      lines, whereas FA, DHCA and DHFA had lower and variable effects. Caffeine had no
      effect. Dietary-attainable concentrations (0.1, 1 and 10 MUg/mL) of YME were
      tested for cytotoxicity and reactive oxygen species generation, showing no
      cytotoxic effect. Low concentrations of all tested compounds were non-cytotoxic
      to CCD-18Co cells. CONCLUSION: YME and to a lower degree GCBE, their phenolic
      components and metabolites may decrease cancer cell viability and proliferation.

PMID- 28506700
TI  - Synergistic antimutagenic effect of isothiocyanates against varied mutagens.
AB  - Although plant foods provide an array of nutrients in the human diet, our
      knowledge of how these nutrients are interacting among each other at molecular
      level is limited. Among these, glucosinolates are the most important secondary
      metabolites, which are readily hydrolyzed to a variety of products including
      isothiocyanates. The current study emphasizes on the antimutagenic potential of
      three isothiocyanates (ITCs) viz. allyl, benzyl and 3-butenyl ITCs (individually
      and in binary combinations) in Ames Salmonella histidine reversion assay using
      Salmonella typhimurium TA98 and TA100 tester strains. Three different mutagens
      were used in the study including two direct acting mutagens [4-nitro-o
      phenylenediamine (frame shift mutagen) and sodium azide (base substitution
      mutagen)] and one indirect acting mutagen [2-aminofluorene]. Furthermore, S9
      fraction from rat liver microsomes was used to mimic the mammalian system. The
      study points towards the ability of ITCs to act as potent inhibitors of
      mutagenicity induced by different mutagens. Benzyl ITC was found to be the most
      effective among the three. Computation of combination effects was done on the
      basis of combination index values. It was observed that ITCs in combination
      induced a stronger antimutagenic response and that too at relatively low
      concentrations, without any signs of toxicity.

PMID- 28506699
TI  - CRA(Crosolic Acid) isolated from Actinidia valvata Dunn.Radix induces apoptosis
      of human gastric cancer cell line BGC823 in vitro via down-regulation of the NF
      kappaB pathway.
AB  - A natural ursolic compound, 2alpha,3beta-dihydroxy-urs-12-en-28-oic acid
      (corosolic acid, CRA) was isolated from the root of Actinidia valvata Dunn. (A.
      valvata Radix). Since a large number of triterpenoid compound has marked
      anticancer effects toward various types of cancer cell lines in vitro, this study
      was carried out to investigate the anticancer effect of CRA in human gastric
      cancer cell line BGC823 cells and the underlying apoptotic mechanism of CRA was
      examined in BGC823 cell lines. The results showed that CRA significantly
      suppressed the viability of BGC823 cells in a concentration- and time-dependent
      manner. CRA also significantly increased the sub G1 population by cell cycle
      analysis in a concentration dependent manner. Exposure to CRA decreased p65, bcl
      2, Fas, smac mRNA and protein expression, and increased IkappaBalpha, bax,
      survivin mRNA and protein expression. Results of immunofluorescence staining and
      EMSA further indicated CRA induced apoptosis by inhibiting nuclear translocation
      of nuclear factor NF-kappaB subunit p65. Consistently overall, our findings
      suggest that CRA induces apoptosis via inhibition of NF-kappaB (p65) expression
      level and activation of IkappaBalpha in BGC cells as a potent anticancer
      candidate for gastric cancer treatment.

PMID- 28506701
TI  - Case-Control Study of Intra-arterial Verapamil for Intraprostatic Anastomoses to
      Extraprostatic Arteries in Prostatic Artery Embolization for Benign Prostatic
      Hypertrophy.
AB  - PURPOSE: It is hypothesized that intra-arterial administration of verapamil is a
      safe and effective way to reverse the flow in intraprostatic anastomoses to
      extraprostatic arteries without compromising treatment outcomes in prostatic
      artery embolization (PAE) for benign prostatic hypertrophy (BPH). MATERIALS AND
      METHODS: A prospective study of 62 prostate sides in 31 consecutive patients
      (median age, 66 y; range, 60-71 y) with symptomatic BPH was undertaken. Median
      prostate volume was 72.4 mL (range, 48.8-85.8 mL), median International Prostate
      Symptom Score was 21 (range, 15-23), and median urine peak flow rate was 4 mL/s
      (range, 2-6 mL/s). The arterial anastomoses were classified as types I-III
      according to vascular morphology. Treatment safety was assessed in terms of
      adverse events and complications, and treatment effectiveness was assessed in
      terms of success rate of angiographic flow reversal. RESULTS: The PAE procedure
      was successfully completed in all 31 patients (100%). Adverse events in both
      groups were transient and mild and did not necessitate prolonged hospitalization.
      There was no clinical evidence of any significant nontarget ischemic complication
      in either group. Intraprostatic anastomosis was diagnosed in 19 of 31 patients
      (61.3%) and 22 of 62 prostate sides (35.5%). Success rates of verapamil treatment
      were 88.9% overall (20 of 22) and 100% (19 of 19) in type II and III anastomoses.
      There was no difference between the treatment group and the control group in
      clinical, urologic, and imaging outcomes of PAE. CONCLUSIONS: Intra-arterial
      verapamil treatment was probably safe and effective in causing flow reversal in
      type II and III intraprostatic anastomoses and in preventing ischemic
      complications in PAE for BPH without compromising PAE outcomes.

PMID- 28506702
TI  - Cognitive and adaptive measurement endpoints for clinical trials in
      mucopolysaccharidoses types I, II, and III: A review of the literature.
AB  - Sensitive, reliable measurement instruments are critical for the evaluation of
      disease progression and new treatments that affect the brain in the
      mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical
      phenotypes that affect the brain during development and result in devastating
      cognitive decline and ultimately death without treatment. Comparisons of outcomes
      are hindered by diverse protocols and approaches to assessment including
      applicability to international trials necessary in rare diseases. We review both
      cognitive and adaptive measures with the goal of providing evidence to a Delphi
      panel to come to a consensus about recommendations for clinical trials for
      various age groups. The results of the consensus panel are reported in an
      accompanying article. The following data were gathered (from internet resources
      and from test manuals) for each measure and summarized in the discussion:
      reliability, validity, date and adequacy of normative data, applicability of the
      measure's metrics, cross cultural validity including translations and
      adaptations, feasibility in the MPS population, familiarity to sites, sensitivity
      to change, and interpretability. If, resulting from this consensus, standard
      protocols are used for both natural history and treatment studies, patients,
      their families, and health care providers will benefit from the ability to
      compare study outcomes.

PMID- 28506703
TI  - Abnormal asymmetry of white matter tracts between ventral posterior cingulate
      cortex and middle temporal gyrus in recent-onset schizophrenia.
AB  - INTRODUCTION: Previous studies have reported abnormalities in the ventral
      posterior cingulate cortex (vPCC) and middle temporal gyrus (MTG) in
      schizophrenia patients. However, it remains unclear whether the white matter
      tracts connecting these structures are impaired in schizophrenia. Our study
      investigated the integrity of these white matter tracts (vPCC-MTG tract) and
      their asymmetry (left versus right side) in patients with recent onset
      schizophrenia. METHOD: Forty-seven patients and 24 age-and sex-matched healthy
      controls were enrolled in this study. We extracted left and right vPCC-MTG tract
      on each side from T1W and diffusion MRI (dMRI) at 3T. We then calculated the
      asymmetry index of diffusion measures of vPCC-MTG tracts as well as volume and
      thickness of vPCC and MTG using the formula: 2*(right-left)/(right+left). We
      compared asymmetry indices between patients and controls and evaluated their
      correlations with the severity of psychiatric symptoms and cognition in patients
      using the Positive and Negative Syndrome Scale (PANSS), video-based social
      cognition scale (VISC) and the Wechsler Adult Intelligence Scale (WAIS-III).
      RESULTS: Asymmetry of fractional anisotropy (FA) and radial diffusivity (RD) in
      the vPCC-MTG tract, while present in healthy controls, was not evident in
      schizophrenia patients. Also, we observed that patients, not healthy controls,
      had a significant FA decrease and RD increase in the left vPCC-MTG tract. There
      was no significant association between the asymmetry indices of dMRI measures and
      IQ, VISC, or PANSS scores in schizophrenia. CONCLUSION: Disruption of asymmetry
      of the vPCC-MTG tract in schizophrenia may contribute to the pathophysiology of
      schizophrenia.

PMID- 28506704
TI  - A method to achieve extended cannabis abstinence in cannabis dependent patients
      with schizophrenia and non-psychiatric controls.
AB  - BACKGROUND: Cannabis use disorders (CUD) are common in schizophrenia (~25%)
      compared to the general population (~3%). Tetrahydrocannabinol (THC), the
      principal psychoactive component in cannabis is fat-soluble, resulting in an
      extended period for cannabinoid elimination. While detection of cannabinoids in
      urine is indicative of prior cannabis exposure, time of last use is difficult to
      verify sustained abstinence for extended periods (e.g., 28-days) in chronic
      cannabis users. Therefore, we evaluated the utility of a sustained cannabis
      abstinence paradigm in patients with schizophrenia and non-psychiatric controls.
      METHODS: Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days
      of monitored cannabis abstinence facilitated with contingency management. Urine
      samples were taken twice weekly. Abstinence was evaluated using 1) Self-report;
      2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of
      participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass
      spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized
      carboxy-THC (THC-COOH) metabolite levels <20ng/mL). Subjective assessments were
      used to assess behavioral correlates of cannabis abstinence and further supported
      time-dependent abstinence trajectories. RESULTS: Abstinence rates of 42.1% (8/19)
      in patients and 55% (11/19) in controls (p=0.53) were observed. Increased
      cannabis withdrawal symptoms in both patients and controls supported abstinence.
      DISCUSSION: Our results suggest a feasible method for identification of short
      term cannabis abstinence in individuals with schizophrenia at rates comparable to
      controls. Monitoring sustained abstinence may have implications for potential
      interventions for CUDs in schizophrenia.

PMID- 28506705
TI  - The interaction of gender and cannabis in early phase psychosis.
AB  - Cannabis is the third most common recreational drug used world-wide after tobacco
      and alcohol. Globally, cannabis legalization is becoming more common. In light of
      its known link to psychosis development, it is imperative that we are well
      informed regarding the impact of cannabis on the course of psychosis, in both
      males and females. However, the majority of the work to date on the role of
      cannabis in psychosis outcomes has not had a gender focus, important when
      considering patient specific treatments. This review examines what is currently
      known, from gender focused studies, about the interaction of gender, cannabis use
      and psychotic disorders.

PMID- 28506706
TI  - Cognitive and functional deficits in people with schizophrenia: Evidence for
      accelerated or exaggerated aging?
AB  - Cognitive and functional deficits are commonly seen in people with schizophrenia.
      The profile of these impairments has a resemblance to the cognitive changes seen
      in healthy aging. In specific, many of the cognitive ability domains that change
      the most with aging in healthy people are the most salient of these deficits seen
      in people with schizophrenia, including prominent deficits in processing speed,
      working memory, and episodic memory. Functional deficits seen in schizophrenia
      are also similar to those seen in healthy aging. There is a relationship between
      multiple psychotic relapses and treatment resistance and longitudinal cognitive
      and functional changes in schizophrenia, with this relationship starting early in
      the course of illness. Cognitive performance in people with schizophrenia may be
      consistent with accelerated or premature aging. People with schizophrenia perform
      similarly to healthy people who are 3 or more decades older on indices of both
      cognition and their everyday functional skills. Some people with schizophrenia
      show exaggerated cognitive changes as well. Cognitive and functional performance
      worsens at the outset of the illness in schizophrenia compared to premorbid
      functioning, meaning that these deficits are not due to development disabilities.
      There are multiple medical and substance abuse comorbidities in schizophrenia and
      although these comorbidities affect cognitive functioning, they are not
      completely responsible for age-related changes.

PMID- 28506707
TI  - Complex mismatch negativity to tone pair deviants in long-term schizophrenia and
      in the first-episode schizophrenia spectrum.
AB  - Mismatch negativity (MMN) is an event-related potential to stimulus change. MMN
      to infrequent deviant tones that differs in a simple physical parameter from
      repetitive standard tones is reduced in patients with long-term schizophrenia
      (Sz; d=~1). However, this simple MMN is not uniformly reduced at the first
      episode of schizophrenia-spectrum psychosis (FESz; d<0.1 for pitch; <0.4 for
      duration). Deviant stimuli that violate pattern rules also evoke MMN. This
      complex MMN is evoked by deviations in the relation of sounds to each other. The
      simplest pattern involves tone pairs. Although the pitch of first tone in the
      pair varies, the second tone's pitch always follows a rule (e.g., always 3
      semitones higher). We measured complex MMN to deviant tone pairs that descended
      in pitch among standard tone pairs that ascended in pitch, never before examined
      in Sz or in FESz. Experiment 1 showed significant reductions in complex MMN in 20
      Sz compared to 22 matched controls. Experiment 2 replicated smaller complex MMN
      in a shorter protocol in 24 Sz compared to 21 matched controls, but showed no
      significant complex MMN reduction in 21 FESz compared to 21 matched controls.
      Although reduced in Sz, indicating deficits in generation of a simple acoustic
      pattern rule, the tone pair complex MMN was within normal limits in FESz. This
      suggests that more complex perceptual pattern analysis processes are, at least
      partially, still intact at the first break. Future work will determine at what
      point of pattern complexity subtle auditory perception pathophysiology will be
      revealed in FESz.

PMID- 28506708
TI  - Electron microscopy approach for the visualization of the epithelial and
      endothelial glycocalyx.
AB  - This study presents a methodological approach for the visualization of the
      glycocalyx by electron microscopy. The glycocalyx is a three dimensional network
      mainly composed of glycolipids, glycoproteins and proteoglycans associated with
      the plasma membrane. Since less than a decade, the epithelial and endothelial
      glycocalyx proved to play an important role in physiology and pathology,
      increasing its research interest especially in vascular functions. Therefore,
      visualization of the glycocalyx requires reliable techniques and its preservation
      remains challenging due to its fragile and dynamic organization, which is highly
      sensitive to the different process steps for electron microscopy sampling. In
      this study, chemical fixation was performed by perfusion as a good alternative to
      conventional fixation. Additional lanthanum nitrate in the fixative enhances
      staining of the glycocalyx in transmission electron microscopy bright field and
      improves its visualization by detecting the elastic scattered electrons, thus
      providing a chemical contrast.

PMID- 28506709
TI  - Behavior of macrophage and osteoblast cell lines in contact with the beta-TCP
      biomaterial (beta-tricalcium phosphate).
AB  - Beta-tricalcium phosphate (beta-TCP) is a synthetic ceramic used for filling bone
      defects. It is a good alternative to autologous grafts since it is biocompatible,
      resorbable and osteoconductive. Previous in vivo studies have shown that
      macrophages are one of the first cells coming in contact with the biomaterial
      followed by osteoclasts and osteoblasts that will elaborate new bone packets.
      Studies have focused on osteoclast morphology and very few of them have
      investigated the role of macrophages. The aims of this study were to characterize
      (i) the biomaterial surface; (ii) the in vitro behavior of macrophages (J774.2
      and Raw264.7 cells) using the description of cell morphology by scanning electron
      microscopy (SEM) at 7 and 14 days; (iii) the behavior of osteoblasts (SaOs-2 and
      MC3T3-E1 cells) seeded at the surface of the biomaterial 24, 48 and 72hours by
      SEM and confocal microscopy. Cell proliferation was analyzed by MTT assays.
      Viability and affinity of the macrophages for beta-TCP were found significantly
      increased after 7 and 14d. MC3T3-E1 cells were anchored and stretched onto the
      beta-TCP surface as early as 24h with a high proliferation rate (+190%) when
      compared to the surface of a well plate. SaOs-2 exhibited the same morphological
      profile at 72h. Proliferation became significantly higher compared to the plastic
      surface at only 72h (+129%). This study emphasises the importance of choice of
      the cell line used in exploring the osteoconductive and osteoinductive properties
      of a biomaterial. Additional studies are needed to analyze differentiation of
      macrophages into giant multinucleated cells and how the biomaterial surface
      influences osteoblast differentiation.

PMID- 28506710
TI  - Outcomes after repeat ablation of ventricular tachycardia in structural heart
      disease: An analysis from the International VT Ablation Center Collaborative
      Group.
AB  - BACKGROUND: Data evaluating repeat radiofrequency ablation (>1RFA) of ventricular
      tachycardia (VT) are limited. OBJECTIVE: The purpose of this study was to
      determine the safety and outcomes of VT >1RFA in patients with structural heart
      disease. METHODS: Patients with structural heart disease undergoing VT RFA at 12
      centers with data on prior RFA history were included. Characteristics and
      outcomes were compared between first-time (1RFA) and >1RFA patients. RESULTS: Of
      1990 patients, 740 had >1RFA (mean 1.4 +/- 0.9, range 1-10). >1RFA vs 1RFA
      patients did not differ with regard to age (62 +/- 13 years vs 62 +/- 13 years),
      left ventricular ejection fraction (33% +/- 13% vs 34% +/- 13%), or sex (88% vs
      87% men), but they more often were nonischemic (53% vs 41%), had implantable
      cardioverter-defibrillator shocks (70% vs 63%) or VT storm (38% vs 33%), and had
      been treated with amiodarone (55% vs 48%) or >=2 antiarrhythmic drugs (22% vs
      14%). >1RFA procedures were longer (300 +/- 122 minutes vs 266 +/- 110 minutes),
      involved more epicardial access (41% vs 21%), induced VTs (2.4 +/- 2.2 vs 1.9 +/-
      1.6) and only unmappable VTs (15% vs 9%), and VT was more often inducible after
      RFA (42% vs 33%, all P <.03). Total complications were higher for >1RFA vs 1RFA
      (8% vs 5%, P <.01), mostly related to pericardial effusion (2.4% vs 1.3%, P =
      .07) and venous thrombosis (0.8% vs 0.2%, P = .06). VT recurrence was higher for
      >1RFA vs 1RFA (29% vs 24%, P <.001). Survival was worse for >1RFA vs 1RFA if VT
      recurred (67% vs 78%, P = .003) but was equivalent if successful (93% vs 92%, P =
      .96). CONCLUSION: Patients requiring repeat VT ablation differ significantly from
      those undergoing first-time ablation. Despite more challenging ablation
      characteristics, VT-free survival after repeat ablations is encouraging.
      Mortality is comparable if VT does not recur after RFA at specialized centers.

PMID- 28506711
TI  - Screening for sepsis in general hospitalized patients: a systematic review.
AB  - BACKGROUND: Sepsis is a condition widely observed outside critical care areas.
      AIM: To examine the application of sepsis screening tools for early recognition
      of sepsis in general hospitalized patients to: (i) identify the accuracy of these
      tools; (ii) determine the outcomes associated with their implementation; and
      (iii) describe the implementation process. METHODS: A systematic review method
      was used. PubMed, CINAHL, Cochrane, Scopus, Web of Science, and Embase databases
      were systematically searched for primary articles, published from January 1990 to
      June 2016, that investigated screening tools or alert mechanisms for early
      identification of sepsis in adult general hospitalized patients. The review
      protocol was registered with PROSPERO (CRD42016042261). FINDINGS: More than 8000
      citations were screened for eligibility after duplicates had been removed. Six
      articles met the inclusion criteria testing two types of sepsis screening tools.
      Electronic tools can capture, recognize abnormal variables, and activate an alert
      in real time. However, accuracy of these tools was inconsistent across studies
      with only one demonstrating high specificity and sensitivity. Paper-based, nurse
      led screening tools appear to be more sensitive in the identification of septic
      patients but were only studied in small samples and particular populations. The
      process of care measures appears to be enhanced; however, demonstrating improved
      outcomes is more challenging. Implementation details are rarely reported.
      Heterogeneity of studies prevented meta-analysis. CONCLUSION: Clinicians,
      researchers and health decision-makers should consider these findings and
      limitations when implementing screening tools, research or policy on sepsis
      recognition in general hospitalized patients.

PMID- 28506712
TI  - Lung Metastases from Esophageal Granular Cell Tumor: An Undoubted Criterion for
      Malignancy.

PMID- 28506713
TI  - The Emperor's new topology: Comment on "Topodynamics of metastable brains" by
      Arturo Tozzi et al.

PMID- 28506714
TI  - The Physics Inside our Brain: Comment on "Topodynamics of Metastable Brains" by
      Arturo Tozzi et al.

PMID- 28506716
TI  - MEK Retinopathy. Clinical case reports.
AB  - CASE REPORTS: Three clinical cases are presented of MEK retinopathy associated
      with the combination of cobimetinib and vemurafenib characterised by alteration
      of the retinal pigment epithelium and neurosensory detachment. Two of the cases
      conserved the vision of the unit, and the third developed a large bilateral
      neurosensory detachment with final visual acuity of 0.6 for the right eye and 0.1
      for the left one. DISCUSSION: The new therapeutic strategies against metastatic
      cutaneous melanoma condition the appearance of alterations of the pigmentary
      epithelium of the retina with serous detachments, leading to close monitoring
      with macular optical coherence tomography.

PMID- 28506717
TI  - Torpedo maculopathy with serous detachment of retinal pigment epithelium.

PMID- 28506715
TI  - Geographic and population-level disparities in colorectal cancer testing: A
      multilevel analysis of Medicaid and commercial claims data.
AB  - Morbidity and mortality from colorectal cancer (CRC) can be attenuated through
      guideline concordant screening and intervention. This study used Medicaid and
      commercial claims data to examine individual and geographic factors associated
      with CRC testing rates in one state (Oregon). A total of 64,711 beneficiaries
      (4516 Medicaid; 60,195 Commercial) became newly age-eligible for CRC screening
      and met inclusion criteria (e.g., continuously enrolled, no prior history) during
      the study period (January 2010-December 2013). We estimated multilevel models to
      examine predictors for CRC testing, including individual (e.g., gender,
      insurance, rurality, access to care, distance to endoscopy facility) and
      geographic factors at the county level (e.g., poverty, uninsurance). Despite
      insurance coverage, only two out of five (42%) beneficiaries had evidence of CRC
      testing during the four year study window. CRC testing varied from 22.4% to 46.8%
      across Oregon's 36 counties; counties with higher levels of socioeconomic
      deprivation had lower levels of testing. After controlling for age, beneficiaries
      had greater odds of receiving CRC testing if they were female (OR 1.04, 95% CI
      1.01-1.08), commercially insured, or urban residents (OR 1.14, 95% CI 1.07-1.21).
      Accessing primary care (OR 2.47, 95% CI 2.37-2.57), but not distance to endoscopy
      (OR 0.98, 95% CI 0.92-1.03) was associated with testing. CRC testing in newly age
      eligible Medicaid and commercial members remains markedly low. Disparities exist
      by gender, geographic residence, insurance coverage, and access to primary care.
      Work remains to increase CRC testing to acceptable levels, and to select and
      implement interventions targeting the counties and populations in greatest need.

PMID- 28506718
TI  - G-Quadruplex surveillance in BCL-2 gene: a promising therapeutic intervention in
      cancer treatment.
AB  - Recently, therapeutic implications of BCL-2 quadruplex invigorated the field of
      clinical oncology. This Keynote review discusses how a BCL-2 quadruplex-selective
      approach circumvents the limitations of existing therapeutics; and which
      improvisations might ameliorate the recent trends of quadruplex-based treatment.

PMID- 28506719
TI  - Two fatalities associated with synthetic opioids: AH-7921 and MT-45.
AB  - In this study, two fatalities associated with the synthetic opioids AH-7921 and
      MT-45 are reported. Within the last few years, both compounds have emerged on the
      recreational drug market and are sold as "research chemicals" on the internet. In
      the first case, a 22-year-old woman was found dead in the bedroom of her
      apartment by two of her friends. A plastic bag labeled "AH-7921" was found in the
      apartment and the two friends stated that the deceased had consumed AH-7921 prior
      to her death. The woman was a known drug addict. In the second case, a 24-year
      old man was found dead in his room by his mother. The deceased was sitting on a
      chair in front of his desk slumped over. Several bags of white powder labeled "MT
      45", "Methoxmetamine" and "Methoxphenidine" were found in his room. Toxicological
      analyses of femoral blood, heart blood, liver, pericardial fluid, urine, vitreous
      humor and stomach content of the deceased were performed using liquid
      chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Time-of
      flight mass spectrometry was carried out on an LC-Triple TOF 5600 system (AB
      Sciex) with electrospray ionization operated in positive mode. In the first case,
      additional hair analysis was performed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and LC-QTOF-MS. In both cases, the relevant synthetic
      opioid could be detected in all analyzed samples. The concentration of AH-7921
      was determined to be 450MUg/L in femoral blood. MT-45 was present at a
      concentration of 2900MUg/L in femoral blood. Besides methoxmetamine which could
      qualitatively be detected in femoral blood, urine and stomach content no
      methoxphenidine was found. In summary, deaths of the young individuals could be,
      by exclusion of other causes of death, attributed to the consumption of an
      overdose of AH-7921 and MT-45, respectively.

PMID- 28506720
TI  - Sunlight-activated near-infrared phosphorescence as a viable means of latent
      fingermark visualisation.
AB  - The chromium-doped zinc gallogermanate, Zn3Ga2Ge2O10:0.5%Cr3+, was prepared and
      modified for use as a near-infrared (NIR) luminescent fingerprint dusting powder.
      The optical properties of this material are illustrated and have been shown to
      offer versatility and promise in terms of overcoming troublesome backgrounds
      during latent fingermark examination and imaging. The highly fluorescent NIR
      emission of the powder allows inherently fluorescent and patterned substrate
      backgrounds to be mitigated, whilst the phosphorescent nature of the material
      allows all conceivable background interference to be removed, whilst also
      constituting the first reported use of a NIR phosphor for latent fingermark
      enhancement and imaging.

PMID- 28506721
TI  - First report of NDM-1-producing clinical isolate of Leclercia adecarboxylata in
      Spain.
AB  - We describe the case of NDM-1-producing Leclercia adecarboxylata recovered from
      the clinical sample of a patient hospitalized for a trauma-related injury to his
      foot. The isolate was resistant to all beta-lactams, quinolones, trimetroprim
      sulfametoxazol, gentamicin and tobramicyn. The blaNDM-1 gene was located in a
      conjugative plasmid that also contained the blaSHV-12 gene and was preceded by a
      disrupted insertion sequence of ISAba125. The plasmid belongs to the
      incompatibility group X3, which is known to be an important vector for NDM-1
      dissemination in China. This is the first reported case of NDM-1L. adecarboxylata
      in our country and evidences that species of uncertain clinical relevance can act
      as hidden sources of clinically important resistance determinants.

PMID- 28506722
TI  - Primary Helicobacter pylori resistance in elderly patients over 20 years: A
      Bulgarian study.
AB  - We evaluated the antibiotic susceptibility of 233 Helicobacter pylori strains
      isolated in the period 2011-2016, involving 62 strains from elderly patients aged
      66-93years and 171 strains from younger adults. To assess resistance evolution,
      primary resistance rates in 92 strains from as many patients aged >=60years in
      1996-2003 were compared with those in 85 strains from infected patients in the
      same age group in 2011-2016. In the patients aged >65years evaluated during the
      last 6 years, amoxicillin resistance according to EUCAST and prior breakpoints
      was 1.6 and 0%, respectively. Resistance rates were the same by both breakpoint
      systems to metronidazole (35.5%), clarithromycin (22.6%), tetracycline (1.6%) and
      levofloxacin (32.3%). In 2011-2016, there were no significant differences between
      resistance rates in the subjects aged >65years and the younger adults. Notably,
      during the last 6 years, double/triple resistance was found in 21.0% of the
      subjects aged >65years. Moreover, the prevalence of quinolone primary resistance
      (30.0%) was significantly (3.4-fold) higher than that (8.9%) observed in 1996
      2003. Briefly, the presence of both combined resistance and a strikingly high
      primary levofloxacin resistance in the elderly implies a cautious antibiotic
      choice for H. pylori eradication. In vitro susceptibility testing of the strains
      is highly important in this age group. The results can be linked to more frequent
      comorbidities and co-infection treatment in older compared with younger patients
      and, additionally, to the national antibiotic consumption. The high prevalence of
      quinolone resistance in the elderly patients is an alarming finding.

PMID- 28506723
TI  - A chronicle of surgical thinking and doing for exotropia: innovations and
      rediscoveries.
AB  - PURPOSE: To review the evolution of theories and practices concerning surgery for
      exotropia over the last approximately 200 years. METHODS: Major ophthalmology
      texts and relevant references were reviewed to discover experience and thinking
      concerning the causes of comitant intermittent and constant exotropia and
      corrective surgical approaches. RESULTS: The concept that excessive divergence is
      the cause of comitant exotropia has given way to one recognizing that this
      disorder is a position of rest modified by convergence. Some operations discarded
      as unreliable or dangerous remain so today. Others continue to be well accepted,
      whether or not relating to advances in understanding of this condition. Several
      procedures practiced at former times have regained popularity. CONCLUSIONS:
      Concern for the characteristics of extraocular muscle structure and function has
      led to surgical thinking that goes beyond consideration only of direction and
      magnitude of deviation. Sophisticated devices now provide heretofore unavailable
      information consistent with this new approach. The history of progress in surgery
      for exotropia is mixed. Although some procedures now employed are new, others
      currently in favor had been well known and formerly utilized by ophthalmologists
      for many decades. These should be regarded as rediscoveries or revivals rather
      than as novel. This review also suggests a need to address how to better report
      retrospective studies.

PMID- 28506724
TI  - Validation of WINROP for detecting retinopathy of prematurity in a North American
      cohort of preterm infants.
AB  - BACKGROUND: WINROP (weight, insulin-like growth factor 1, neonatal, retinopathy
      of prematurity) is a web-based retinopathy of prematurity (ROP) risk algorithm
      that uses postnatal weight gain as a surrogate of insulin-like growth factor-1
      (IGF-1) to predict the risk of severe ROP in premature infants. The purpose of
      this study was to validate the web-based algorithm WINROP in detecting severe
      (type 1 or type 2) ROP in a North American cohort of infants. METHODS: The
      records of consecutive infants who underwent ROP examinations between 2008 and
      2011 were reviewed retrospectively. Infants were classified into categories of
      "alarm" (at risk for developing severe ROP) and "no alarm" (minimal risk for
      severe ROP). RESULTS: A total of 483 were included. Alarm occurred in 241
      neonates (50%), with the median time from birth to alarm of 2 weeks. WINROP had a
      sensitivity of 81.8% (95% CI, 67.3%-91.8%) and specificity of 53.3% (95% CI,
      48.5%-58.0%) for identifying infants with severe ROP. Eight of the 44 infants
      with severe ROP were not detected (5 with type 1 and 3 with type 2). Of these 8
      infants, 7 (88%) had birth weight in excess of the 70th pecentile. With
      additional weight data entry, sensitivity of WINROP rose to 88.6%. CONCLUSIONS:
      Very preterm infants (gestational age of <=27 weeks) with relatively high birth
      weight for gestational age may not be detected by WINROP as high risk for
      developing severe ROP.

PMID- 28506725
TI  - The first invertebrate NFIL3 transcription factor with role in immune defense
      identified from the Hong Kong oyster, Crassostrea hongkongensis.
AB  - NFIL3 (nuclear factor interleukin 3-regulated) is a basic leucine zipper type
      transcription factor that mediates a variety of immune responses in vertebrates.
      However, the sequence information and function of NFIL3 homologs in
      invertebrates, especially mollusks, remains unknown. In the present study, the
      first NFIL3 homolog was identified in a marine mollusk, Crassostrea hongkongensis
      (designated as ChNFIL3), followed by its functional characterization. The full
      length cDNA of ChNFIL3 is 2221 bp and consists of an open reading frame (ORF) of
      1536 bp that encodes a polypeptide of 551 amino acids. Simple Modular
      Architecture Research Tool (SMART) analysis indicated that ChNFIL3 has two basic
      leucin zipper domains, similar to the other known NFIL3 family proteins. Tissue
      distribution analysis of NFIL3 in this mollusk revealed high expression in
      digestive glands and hemocytes. A significant induction in the mRNA level of
      ChNFIL3 was observed following bacterial stimulation. ChNFIL3 was found to be
      localized in the nucleus and over expression of ChNIFL3 led to upregulation of
      transcriptional activity of an NF-kappaB reporter gene in HEK 293T cells,
      indicating its role in innate immunity. Furthermore, addition of exogenous
      recombinant ChNFIL3 proteins resulted in enhanced mRNA level of hemocyte
      interleukin 17 in vitro. In conclusion, our findings revealed that NFIL3 in
      molluscs, plays a conserved role in host defense, similar to its mammalian
      homolog.

PMID- 28506726
TI  - Influence of xanthan, guar, CMC and gum acacia on functional properties of water
      chestnut (Trapa bispinosa) starch.
AB  - This study was performed to determine the effect of xanthan, guar, CMC and gum
      acacia on functional and pasting properties of starch isolated from water
      chestnut (Trapa bispinosa). Morphological properties of water chestnut starch
      with CMC were studied by scanning electron microscopy (SEM). The addition of
      hydrocolloids significantly enhanced the solubility of water chestnut starch
      (WCS) while reduced swelling power and freeze-thaw stability. The hydrophilic
      tendency of WCS was increased by xanthan gum; however, with addition of gum
      acacia it decreased significantly. Starch was modified with guar and gum acacia
      exhibited highest% syneresis. Guar gum was found to be effective in increasing
      the clarity of water chestnut starch paste. The addition of CMC significantly
      reduced the pasting temperature of WCS indicating ease of gelatinization. The
      setback was accelerated in the presence of xanthan gum but gum acacia delayed
      this effect during the cooling of the starch paste. Only xanthan gum was found to
      be effective in increasing breakdown showing good paste stability of WCS.

PMID- 28506727
TI  - [Differences and similarities between occupational and tobacco induced COPD].
AB  - Chronic obstructive pulmonary disease (COPD) most often results from the
      inhalation of toxic agents. Cigarette smoking still remains the principal cause
      but the pertinence of occupational COPD is now clearly established. After a brief
      overview of the epidemiology of this "other COPD", the clinical and functional
      characteristics are summarized, taking into account recent advances in this
      field. The combined effects of occupational exposure and tobacco are also
      considered, providing evidence of the need to continuously reinforce campaigns of
      education and prevention in occupational COPD.

PMID- 28506728
TI  - [The effects of inhaled steroids withdrawal in COPD].
AB  - The key pathophysiological feature of chronic obstructive pulmonary disease
      (COPD) is an abnormal inflammatory bronchial reaction after inhalation of toxic
      substances. The priority is the avoidance of such toxic inhalations, but the use
      of anti-inflammatory drugs also seems appropriate, especially corticosteroids
      that are the sole anti-inflammatory drug available for this purpose in France.
      The risks associated with the prolonged use of these parenteral drugs are well
      known. Inhalation is therefore the optimal route, but inhaled drugs may also lead
      to adverse consequences. In COPD, there is an inhaled corticosteroids overuse,
      and a non-satisfactory respect of the guidelines. Consequently, their withdrawal
      should be considered. We reviewed seven clinical studies dealing with inhaled
      corticosteroids withdrawal in patients with COPD and found that included
      populations were heterogenous with different concomitant treatments. In non
      frequent exacerbators receiving inhaled corticosteroids outside the
      recommendations, withdrawal appears to be safe under a well-managed
      bronchodilator treatment. In patients with severe COPD and frequent
      exacerbations, the risk of acute respiratory event is low when they receive
      concomitant optimal inhaled bronchodilators. However, other risks may be observed
      (declining lung function, quality of life) and a discussion of each case should
      be performed, especially in case of COPD and asthma overlap.

PMID- 28506729
TI  - [The role of extracorporeal removal of CO2 (ECCO2R) in the management of
      respiratory diseases].
AB  - INTRODUCTION: The aim of extracorporeal removal of CO2 (ECCO2R) is to ensure the
      removal of CO2 without any significant effect on oxygenation. ECCO2R makes use of
      low to moderate extracorporeal blood flow rates, whereas extracorporeal membrane
      oxygenation (ECMO) requires high blood flows. STATE OF THE ART: For each ECCO2R
      device it is important to consider not only performance in terms of CO2 removal,
      but also cost and safety, including the incidence of hemolysis and of hemorrhagic
      and thrombotic complications. In addition, it is possible that the benefits of
      such techniques may extend beyond simple removal of CO2. There have been
      preliminary reports of benefits in terms of reduced respiratory muscle workload.
      Mobilization of endothelial progenitor cells could also occur, in analogy to the
      data reported with ECMO, with a potential benefit in term of pulmonary repair.
      The most convincing clinical experience has been reported in the context of the
      acute respiratory distress syndrome (ARDS) and severe acute exacerbations of
      chronic obstructive pulmonary disease (COPD), especially in patients at high risk
      of failure of non-invasive ventilation. PERSPECTIVES: Preliminary results prompt
      the initiation of randomized controlled trials in these two main indications.
      Finally, the development of these technologies opens new perspectives in terms of
      long-term ventilatory support.

PMID- 28506730
TI  - [The human gut microbiota: Interactions with the host and dysfunctions].
AB  - The human intestinal microbiota is composed of approximately 100,000 billion
      microorganisms with the average total number of different commensal bacterial
      species estimated at over 500 per individual. The human intestinal microbiota can
      be considered as an organ within another, which co-evolved with its host to
      achieve a symbiotic relationship leading to physiological homeostasis. The host
      provides an environment enriched in nutrients and the microbiota provides
      essential functions. Dysbiosis of the intestinal microbiota (changes in bacterial
      composition) has been associated with local dysfunctions of the gastrointestinal
      tract, such as inflammatory bowel disease or irritable bowel syndrome but also
      with obesity and metabolic diseases. However, a better understanding of the human
      intestinal ecosystem is still needed to understand the exact role of the
      microbiota in health and disease. Most intestinal bacteria are anaerobic and
      therefore, for the large majority, impossible to culture at present.
      Consequently, their function cannot be inferred from data on their composition.
      Today, with the help of a metagenomic approach, the bacterial genomic content of
      an ecosystem and the associated functions can be directly accessed from the
      environment without culture.

PMID- 28506731
TI  - Risk of Heart Failure in Obese Patients With and Without Bariatric Surgery in
      Sweden-A Registry-Based Study.
AB  - BACKGROUND: Obesity is a known risk factor for heart failure. The prevalence of
      both conditions has increased in Sweden during the past several decades. Obesity
      surgery has been shown to improve cardiac function. We therefore investigated
      whether the risk of heart failure was lower in obese patients after bariatric
      surgery compared with obese patients without surgical intervention. METHODS AND
      RESULTS: From the Swedish National Patient Registry. we created a cohort
      including 47,859 patients aged 18-74 years with a primary diagnosis of obesity
      from 2000 to 2011. Of these, 22,295 (46.6%) underwent bariatric surgery (mean age
      40.7 (standard deviation [SD] 10.7) years, 75.9% female). There were 25,564
      (53.4%) nonsurgical obese patients (mean age 44.3 (SD 13.2) years, 66.8% female).
      Patients who underwent bariatric surgery had a markedly reduced risk of heart
      failure compared with nonsurgical obese patients (age- and sex-adjusted hazard
      ratio [HR] 0.37, 95% confidence interval [CI] 0.29-0.46). The lower risk
      persisted after further adjustment for baseline differences in known risk factors
      for heart failure (HR 0.37, 95% CI 0.30-0.46). CONCLUSION: Patients who underwent
      bariatric surgery had a reduced risk of heart failure after surgery compared with
      nonsurgical obese patients.

PMID- 28506732
TI  - Primary seminal vesicle carcinoma. The usefulness of PAX8 immunohistochemical
      expression for the differential diagnosis.
AB  - Primary seminal vesicle carcinoma is a rare entity whose diagnosis can be
      achieved by ruling out the main carcinomas that commonly invade the seminal
      vesicles. Although a panel of immunohistochemical markers (cancer antigen 125,
      cytokeratin [CK] 7, CK20, prostate-specific antigen, and prostate-specific acid
      phosphatase) has been proposed as unique for primary seminal vesicle carcinoma, a
      reliable positive marker is lacking. In this article, we report a case of primary
      seminal vesicle carcinoma in a 57-year-old man. The tumor was localized to the
      left seminal vesicle and histologically characterized by papillae lined by broad
      eosinophilic cells with pleomorphic nuclei. The neoplastic cells expressed cancer
      antigen 125 and CK7, whereas CK20, prostate-specific antigen, and prostate
      specific acid phosphatase were negative. A strong and diffuse nuclear labeling
      for PAX8 was detected. Because carcinomas of the colon, bladder, and prostate,
      the main differential diagnosis in this setting, have been reported consistently
      to be PAX8 negative, this marker may be very useful for a prompt diagnosis of
      seminal vesicle carcinoma.

PMID- 28506733
TI  - Variant morphology in upper urinary tract urothelial carcinoma: a 14-year case
      series of biopsy and resection specimens.
AB  - Upper urinary tract urothelial carcinoma exhibiting variant morphology,
      especially in higher-grade tumors, is a recognized phenomenon but has not been
      comparatively studied in biopsy versus resection material. We studied the
      morphologic patterns and clinicopathological features, and provide a comparison
      between biopsy and resection specimens. Consultation cases were evaluated
      separately to investigate for possible consultation bias. A total of 383 in-house
      cases from 352 patients including 314 resection specimens and 69 biopsies from
      2001 to 2014 were reviewed from a single institution. Histologic type, tumor
      grade, invasion, pathologic stage, nodal status, metastasis, and the presence and
      type of variant morphology for each case were evaluated. Variant morphology was
      identified in 5 biopsy specimens (7.2%) and 42 resection specimens (13.4%). The
      most common variant morphologic pattern was squamous differentiation (16 cases,
      4.5%) followed by an inverted growth pattern (8 cases, 2.2%). The presence of
      variant morphology in resection specimens had a significant association with
      higher tumor grade, higher pT stage, and nonpapillary configuration. Of 69
      patients with biopsies, 31 had a subsequent resection. In comparison, 181
      consultation cases from 168 patients showed variant morphology in 6 biopsies
      (7.1%) and 27 resections (28.1%). In conclusion, the frequency of recognizing
      variant morphology in biopsies is about one-half of that in resections. The
      inclusion of consultation cases can inflate the incidence of variant morphology.
      As a result, the frequency of variant morphology in our in-house cases is lower
      than the percentage reported in the literature, most likely secondary to a
      consultation bias.

PMID- 28506736
TI  - Editorial Comment.

PMID- 28506734
TI  - mTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma.
AB  - Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular
      neoplasm with no known cure, high recurrence rates, and potential for wide
      dissemination. Low efficacy and high toxicity limit current therapeutic options
      for advanced disease. Activation of mammalian target of rapamycin (mTOR),
      platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF),
      and c-kit signaling pathways has been implicated in KS pathogenesis and may
      suggest a role for targeted inhibitors. KS cases were retrospectively retrieved
      (N=274), most (90%) associated with human immunodeficiency virus. Tissue
      microarray slides were stained with human herpes virus-8, Friend leukemia
      integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF
      receptor-beta, VEGF, and phospho-mTOR. Both intensity and extent of staining were
      scored. Multiplying these scores for each core yielded total staining H-scores.
      Human herpes virus-8 was positive in 87% and Friend leukemia integration 1
      transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+
      (95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were
      phospho-mTOR+. There was no significant difference in staining among patients
      with low (<500 cells/mm3) or preserved CD4 T-cell counts. Immunohistochemistry
      confirms upregulation of the mTOR, PDGF, VEGF, and c-kit pathways in a large
      cohort of KS samples. Of proteins tested, pS6, downstream of mTOR, demonstrated
      the highest proportion of strong positivity (67.1%). These results support the
      possibility of using targeted inhibitors in KS. Overexpression was independent of
      CD4 count, suggesting that even patients with low counts may be targeted therapy
      candidates.

PMID- 28506735
TI  - A proposal for standardization of transgenic reference sequences used in food
      forensics.

PMID- 28506737
TI  - Detection of genital chlamydial and gonococcal infection using urine samples: A
      community-based study from India.
AB  - Sexually transmitted infections (STI) have a major impact on the reproductive
      health of women. Among the different etiological agents of STIs, Chlamydia
      trachomatis and Neisseria gonorrhoeae are the main bacterial pathogens that cause
      sexually transmitted infections in women. The aim of the study was to estimate
      the prevalence of genital chlamydial and gonococcal infection among women in the
      age group of 18-65 years from a community-based setting. A community-based cross
      sectional study was performed using the archived urine samples (n=811) of women
      in the age group of 18-65 years for C. trachomatis and N. gonorrhoeae using a
      multiplex conventional Polymerase Chain Reaction (PCR). Out of 811 samples tested
      in the present study, 2 (0.24%) were tested positive for C. trachomatis and none
      were positive for N. gonorrhoeae. The study demonstrates the very low prevalence
      of C. trachomatis and N. gonorrhoeae infection in a rural community. For large
      population-based screening, urine samples were observed to be more socially
      acceptable and cost-effective.

PMID- 28506738
TI  - [Mental disorders and their underdiagnosis in primary care].
AB  - : Despite its high prevalence, mental disorders are often underdiagnosed.
      OBJECTIVE: To determine the magnitude of the underdiagnosis mental disorders and
      its associated characteristics. METHODOLOGY: A descriptive cross-sectional study
      performed in Lanzarote (2011) on 310 patients selected by cluster random
      sampling. A self-completed questionnaire was used that contained the General
      Health Questionnaire-28, as well as structured interview using the Mini
      International Neuropsychiatric Interview to confirm the diagnosis of mental
      disorder. The current diagnosis registered in the DRAGO-AP electronic medical
      record was also recorded. RESULTS: Of the 75 patients detected with the
      interview, 14 (18.67%) had a diagnosis recorded in the medical record
      (sensitivity=0.19; IC 95% CI; 0.09-28). The positive predictive value of being in
      the medical record was 0.56. With respect to sensitivity, only the "number of
      visits made to the health centre in the last 3 months" was significantly higher
      in the group of patients also with a diagnosis of any mental disorder in the
      medical record (5 vs. 2.77; p=.002). CONCLUSIONS: There is an important
      underdiagnosis of the mental disorders in our environment. More visits to the
      health centre are associated with this diagnosis.

PMID- 28506739
TI  - [Hyperglycaemia as an unusual manifestation of small cell lung carcinoma with
      ectopic adrenocorticotropic hormone secretion].

PMID- 28506740
TI  - [Cause of acute non-surgical abdomen: omental infarction].

PMID- 28506741
TI  - Evaluation of a sound environment intervention in an ICU: A feasibility study.
AB  - BACKGROUND: Currently, it is well known that the sound environment in intensive
      care units (ICU) is substandard. Therefore, there is a need of interventions
      investigating possible improvements. Unfortunately, there are many challenges to
      consider in the design and performance of clinical intervention studies including
      sound measurements and clinical outcomes. OBJECTIVES: (1) explore whether it is
      possible to implement a full-scale intervention study in the ICU concerning sound
      levels and their impact on the development of ICU delirium; (2) discuss
      methodological challenges and solutions for the forthcoming study; (3) conduct an
      analysis of the presence of ICU delirium in the study group; and (4) describe the
      sound pattern in the intervention rooms. METHODS: A quasi-randomized clinical
      trial design was chosen. The intervention consisted of a refurbished two-bed ICU
      patient room (experimental) with a new suspended wall-to-wall ceiling and a low
      frequency absorber. An identical two-bed room (control) remained unchanged.
      INCLUSION CRITERIA: Patients >18 years old with ICU lengths of stay (LoS) >48h.
      The final study group consisted of 31 patients: six from the rebuilt experimental
      room and 25 from the control room. Methodological problems and possible solutions
      were continuously identified and documented. RESULTS: Undertaking a full-scale
      intervention study with continuous measurements of acoustic data in an ICU is
      possible. However, this feasibility study demonstrated some aspects to consider
      before start. The randomization process and the sound measurement procedure must
      be developed. Furthermore, proper education and training are needed for
      determining ICU delirium. CONCLUSION: This study raises a number of points that
      may be helpful for future complex interventions in an ICU. For a full-scale study
      to be completed a continuously updated cost calculation is necessary.
      Furthermore, representatives from the clinic need to be involved in all stages
      during the project.

PMID- 28506742
TI  - Investigation of gene expression and serum levels of PIN1 and eNOS with high
      blood pressure in patients with Alzheimer disease.
AB  - According to evidence, Alzheimer's disease is known as one of the most serious
      neurodegenerative diseases, for which hypertension has been observed to be a key
      risk factor. Therefore, this study aims to examine the relationship between the
      PIN1 and eNOS genes expression, as well as serum levels and hypertension in
      Alzheimer's disease sufferers. Blood samples were obtained from subjects who were
      divided into four groups: the control group, normotensive Alzheimer's patients,
      the Alzheimer's sufferers group with hypertension, and the healthy group with
      only hypertension, considering the inhibition of confounding factors. Thereafter,
      eNOS and PIN1 genes expression along with serum levels were studied. Based on the
      obtained results, a statistically significant correlation didn't exist between
      serum level of PIN1 and the systolic and diastolic blood pressure, between serum
      level of eNOS and diastolic blood pressure in the norm tension Alzheimer's
      disease patients, between serum levels of PIN1, eNOS and systolic blood pressure,
      and between serum eNOS and systolic and diastolic blood pressure in the patients
      with hypertension (p<0.05). According to the results obtained from this study,
      measuring the serum levels of eNOS and Pin1 may contribute to the prognosis,
      prevention, and monitoring of hypertension and also to the reduction of death
      rates from cardiovascular diseases in Alzheimer's disease.

PMID- 28506743
TI  - Peptide ligand-modified nanomedicines for targeting cells at the tumor
      microenvironment.
AB  - Since their initial discovery more than 30years ago, tumor-homing peptides have
      become an increasingly useful tool for targeted delivery of therapeutic and
      diagnostic agents into tumors. Today, it is well accepted that cells at the tumor
      microenvironment (TME) contribute in many ways to cancer development and
      progression. Tumor-homing peptide-decorated nanomedicines can interact
      specifically with surface receptors expressed on cells in the TME, improve
      cellular uptake of nanomedicines by target cells, and impair tumor growth and
      progression. Moreover, peptide ligand-modified nanomedicines can potentially
      accumulate in the target tissue at higher concentrations than would small
      conjugates, thus increasing overall target tissue exposure to the therapeutic
      agent, enhance therapeutic efficacy and reduce side effects. This review
      describes the most studied peptide ligands aimed at targeting cells in the TME,
      discusses major obstacles and principles in the design of ligands for drug
      targeting and provides an overview of homing peptides in ligand-targeted
      nanomedicines that are currently in development for cancer therapy and diagnosis.

PMID- 28506746
TI  - The NAD+-dependent deacetylase, Bifidobacterium longum Sir2 in response to
      oxidative stress by deacetylating SigH (sigmaH) and FOXO3a in Bifidobacterium
      longum and HEK293T cell respectively.
AB  - Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent
      protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3
      and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium
      longum(B.longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene
      family and have antioxidant activity in human body. it remains unknown whether
      probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we
      knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L.acidophilus) in low oxygen
      level. The antioxidant activities of two sir2 deficient strains was decreased,
      while when reintroduction of BL-sir2 and LA-sir2, the antioxidant activities were
      recoveried. In order to understand the regulation mechanism of probiotics Sir2
      oxidation response. Then, we screened 65 acetylated protein, and found that SigH
      (sigmaH) was a substrate of BL-Sir2. In addition, the acetylation level of sigmaH
      decreased with the increase of BL-Sir2 level in B. longum. Thus, BL-Sir2
      deacetylated sigmaH in response to oxidative stress. Next, we transfected BL-Sir2
      into H2O2-induced oxidative damage of 293T cells, BL-Sir2 increased the activity
      of manganese superoxide dismutase (MnSOD/SOD2) and catalase (CAT) and reduced
      reactive oxygen species(ROS). Then, we analyzed the differential gene by RNA
      sequencing and Gene ontology (GO) and found that BL-Sir2 regulated forkhead
      transcription factor (FOXO3a) mediated antioxidant genes in overexpressed BL-Sir2
      HEK293T cells. Our study is the first to link probiotics Sir2 with oxidative
      stress and uncover the antioxidant mechanism of BL-Sir2 in B. longum itself and
      human body.

PMID- 28506747
TI  - Reply.

PMID- 28506748
TI  - Copy number variation analysis of patients with intellectual disability from
      North-West Spain.
AB  - Intellectual disability (ID) is a complex and phenotypically heterogeneous
      neurodevelopmental disorder characterized by significant deficits in cognitive
      and adaptive skills, debuting during the developmental period. In the last
      decade, microarray-based copy number variation (CNV) analysis has been proved as
      a strategy particularly useful in the discovery of loci and candidate genes
      associated with these phenotypes and is widely used in the clinics with a
      diagnostic purpose. In this study, we evaluated the usefulness of two genome-wide
      high density SNP microarrays -Cytogenetics Whole-Genome 2.7M SNP array (n=126
      patients; Group 1) and CytoScan High-Density SNP array (n=447 patients; Group 2)-
      in the detection of clinically relevant CNVs in a cohort of ID patients from
      Galicia (NW Spain). In 159 (27.7%) patients, we detected 186 rare exonic
      chromosomal imbalances, that were grouped into the following classes: Clinically
      relevant (67/186; 36.0%), of unknown clinical significance (93/186; 50.0%) and
      benign (26/186; 14.0%). The 67 pathogenic CNVs were identified in 64 patients,
      which means an overall diagnostic yield of 11.2%. Overall, we confirmed that ID
      is a genetically heterogeneous condition and emphasized the importance of using
      genome-wide high density SNP microarrays in the detection of its genetic causes.
      Additionally, we provided clinical and molecular data of patients with pathogenic
      or likely pathogenic CNVs and discussed the potential implication in
      neurodevelopmental disorders of genes located within these variants.

PMID- 28506749
TI  - Minority College Students' HPV Knowledge, Awareness, and Vaccination History.

PMID- 28506750
TI  - Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines
      of cassaine diterpenoids from the bark of Erythrophleum fordii.
AB  - A phytochemical investigation into the bark of Erythrophleum fordii yielded four
      new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and
      two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as
      nine known compounds. We report for the first time the isolation of erythrofordin
      V (3) from a natural source and that of the remaining eight known diterpenoids (4
      5, 8-13) from E. fordii. All structures were elucidated using spectroscopic
      analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in
      vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and
      NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13)
      exhibited potent cytotoxic activity against all three cell lines with IC50 values
      between 0.4MUM and 5.9MUM. Erythroformine B (7) significantly induced apoptosis
      in all three cancer cells in a concentration-dependent manner.

PMID- 28506751
TI  - Recent progress towards clinically relevant ATP-competitive Akt inhibitors.
AB  - The frequency of PI3K/Akt/mTOR (PAM) Pathway mutations in human cancers sparked
      interest to determine if the pathway is druggable. The modest clinical benefit
      observed with mTOR rapalogs (temsirolimus and everolimus) provided further
      motivation to identify additional nodes of pathway inhibition that lead to
      improved clinical benefit. Akt is a central signaling node of the PAM pathway and
      could be an ideal target for improved pathway inhibition. Furthermore, inhibitors
      of Akt may be especially beneficial in tumors with Akt1 mutations. Recently,
      multiple ATP-competitive Akt inhibitors have been identified and are currently in
      clinical development. This review details the medicinal chemistry efforts towards
      identification of these molecules, highlights relevant preclinical data
      supporting clinical evaluation, and summarizes current clinical development
      plans.

PMID- 28506752
TI  - Thio-functionalized carbohydrate thiosemicarbazones and evaluation of their
      anticancer activity.
AB  - Thiosemicarbazides and their analogs have shown potential medical applications as
      antiviral, antibacterial and anticancer drugs. We designed, synthesized and
      evaluated in vitro anticancer activity against ovarian (A2780), cervix (HeLa),
      colon (LoVo), breast (MCF-7) and brain (MO59J) human cancer cell lines of seven
      novel compounds -S-glycosylated thiosemicarbazones. We assessed the cyto- and
      genotoxic properties of all novel compounds using a variety of methods including
      comet assay, XTT assay, various fluorescent assays and toxicology PathwayFinder
      expression array. We tried to evaluate their possible mechanism of action with
      particular attention to induction of DNA damage and repair, apoptosis, oxidative
      stress analysis and cellular response in terms of changes in gene expression. The
      most sensitive cell line was human ovarian cancer. The results revealed that the
      major activity against A2780 cancer cell line displayed by our compounds is
      induction of DNA damage. This effect is not associated with apoptosis or
      oxidative stress induction and the resulting damage will not lead to cell cycle
      arrest. We also observed up-expression of heat shock related genes and NQO1 gene
      in response to our compounds. The second effect seems to be specific to
      glycosylated S-bond compounds as we observed it earlier. Upregulation of heat
      shock protein encoding genes suggest that our compounds induce stressful
      conditions. The nature of this phenomena (heat shock, pH shift or hypoxia) needs
      further study.

PMID- 28506745
TI  - Applying nanomedicine in maladaptive inflammation and angiogenesis.
AB  - Inflammation and angiogenesis drive the development and progression of multiple
      devastating diseases such as atherosclerosis, cancer, rheumatoid arthritis, and
      inflammatory bowel disease. Though these diseases have very different phenotypic
      consequences, they possess several common pathophysiological features in which
      monocyte recruitment, macrophage polarization, and enhanced vascular permeability
      play critical roles. Thus, developing rational targeting strategies tailored to
      the different stages of the journey of monocytes, from bone marrow to local
      lesions, and their extravasation from the vasculature in diseased tissues will
      advance nanomedicine. The integration of in vivo imaging uniquely allows studying
      nanoparticle kinetics, accumulation, clearance, and biological activity, at
      levels ranging from subcellular to an entire organism, and will shed light on the
      fate of intravenously administered nanomedicines. We anticipate that convergence
      of nanomedicines, biomedical engineering, and life sciences will help to advance
      clinically relevant therapeutics and diagnostic agents for patients with chronic
      inflammatory diseases.

PMID- 28506753
TI  - Phenylbenzenesulfonates and -sulfonamides as 17beta-hydroxysteroid dehydrogenase
      type 2 inhibitors: Synthesis and SAR-analysis.
AB  - 17beta-Hydroxysteroid dehydrogenase type 2 (17beta-HSD2) converts the potent
      estrogen estradiol into the weakly active keto form estrone. Because of its
      expression in bone, inhibition of 17beta-HSD2 provides an attractive strategy for
      the treatment of osteoporosis, a condition that is often caused by a decrease of
      the active sex steroids. Currently, there are no drugs on the market targeting
      17beta-HSD2, but in multiple studies, synthesis and biological evaluation of
      promising 17beta-HSD2 inhibitors have been reported. Our previous work led to the
      identification of phenylbenzenesulfonamides and -sulfonates as new 17beta-HSD2
      inhibitors by ligand-based pharmacophore modeling and virtual screening. In this
      study, new molecules representing this scaffold were synthesized and tested in
      vitro for their 17beta-HSD2 activity to derive more profound structure-activity
      relationship rules.

PMID- 28506754
TI  - Synthesis, biological evaluation and molecular docking studies of chromone
      hydrazone derivatives as alpha-glucosidase inhibitors.
AB  - A series of chromone hydrazone derivatives 4a-4p have been synthesized,
      characterized by 1H NMR and 13C NMR and evaluated for theirinvitro alpha
      glucosidase inhibitory activity. Out of these tested compounds, six (4a, 4b, 4d,
      4j, 4o and 4p) displayed potent alpha-glucosidase inhibitory activity with IC50
      values in the range of 20.1+/-0.19MUM to 45.7+/-0.23MUM, as compared to the
      standard drug acarbose (IC50=817.38+/-6.27MUM). Among this series, compound 4d
      (IC50=20.1+/-0.19MUM) with 4-sulfonamide substitution at phenyl part of hydrazide
      was found to be the most active compound. Lineweaver-Burk plot analysis indicated
      that compound 4d is a non-competitive inhibitor of alpha-glucosidase. The binding
      interactions of the most active analogs were confirmed through molecular docking
      studies. Docking studies showed 4d are interacting with the residues Glu-276, Asp
      214, Asp-349 and Arg-439 through hydrogen bonds, arene-anion and arene-cation
      interactions. In summary, our studies shown that these chromone hydrazone
      derivatives are a new class of alpha-glucosidase inhibitors.

PMID- 28506744
TI  - Hepatic stellate cells as key target in liver fibrosis.
AB  - Progressive liver fibrosis, induced by chronic viral and metabolic disorders,
      leads to more than one million deaths annually via development of cirrhosis,
      although no antifibrotic therapy has been approved to date. Transdifferentiation
      (or "activation") of hepatic stellate cells is the major cellular source of
      matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis.
      Paracrine signals from injured epithelial cells, fibrotic tissue
      microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis,
      and hepatitis viral products can directly or indirectly induce stellate cell
      activation. Dysregulated intracellular signaling, epigenetic changes, and
      cellular stress response represent candidate targets to deactivate stellate cells
      by inducing reversion to inactivated state, cellular senescence, apoptosis,
      and/or clearance by immune cells. Cell type- and target-specific pharmacological
      intervention to therapeutically induce the deactivation will enable more
      effective and less toxic precision antifibrotic therapies.

PMID- 28506755
TI  - [Analysis of the quality of life in patients affected by scoliosis].
AB  - OBJECTIVES: To assess the quality of life using the SRS 22 test in patients with
      scoliosis of 20 or more degrees Cobb. MATERIAL AND METHODS: A prospective
      descriptive study was conducted between April and May 2016 on patients with
      scoliosis of at least 20 degrees Cobb and aged between 10 and 20 years. A record
      was made of weight, height, body mass index, and the SR 22 specific quality of
      life questionnaire for patients with scoliosis was completed. Patients were
      divided into two groups for analysis: a) scoliosis between 20 and 29 degrees Cobb
      (n=44); and b) scoliosis with a Cobb of 30 degrees or greater (n=32). RESULTS:
      There were significant differences in the dimensions that assess pain, image self
      perception, and satisfaction with treatment, being valued worse when the degree
      of scoliosis Cobb is 30 degrees or higher. There were no significant differences
      in function/activity or mental health. The overall score of the questionnaire was
      also worse in the group with the highest degree of scoliosis. The weight, height,
      and BMI showed no significant differences due to the varying degrees of
      scoliosis. CONCLUSIONS: Scoliosis significantly affects the quality of life of
      people who suffer it, and there is a negative correlation between the severity of
      scoliosis measured by degrees Cobb and quality of life.

PMID- 28506756
TI  - [Estimation of the population attributable fraction due to obesity in hospital
      admissions for flu valued according to Body Mass Index (BMI) and CUN-BAE].
AB  - INTRODUCTION: The obesity pandemic together with the influenza pandemic could
      lead to a significant burden of disease. The body mass index (BMI) does not
      discriminate obesity appropriately. The CUN-BAE has recently been used as an
      estimate of body fatness for Caucasians, including BMI, gender, and age. The aim
      of this study is to assess the population attributable fraction of hospital
      admissions due to influenza, due to the body fatness measured with the BMI, and
      the CUN-BAE. METHODS: A multicentre study was conducted using matched case
      controls. Cases were hospital admissions with the influenza confirmed by the RT
      PCR method between 2009 and 2011. The risk of hospital admission and the
      population attribuible fraction were calculated using the BMI or the CUN-BAE for
      each adiposity category in a conditional logical regression analysis adjusted for
      confounding variables. The analyzes were estimated in the total sample, in
      unvaccinated people, and those less than 65 years-old. RESULTS: A total of 472
      hospitalised cases and 493 controls were included in the study. Compared to
      normal weight, the aOR of influenza hospital admissions increases with each level
      of BMI (aOR=1.26; 2.06 and 11.64) and CUN-BAE (aOR=2.78; 4.29; 5.43 and 15.18).
      The population attributable fraction of influenza admissions using CUN-BAE is 3
      times higher than that estimated with BMI (0,72 vs. 0,27), with the differences
      found being similar the non-vaccinated and under 65 year-olds. CONCLUSION: The
      BMI could be underestimating the burden of disease attributable to obesity in
      individuals hospitalised with influenza. There needs to be an appropriate
      assessment of the impact of obesity and vaccine recommendation criteria.

PMID- 28506757
TI  - [Refractory iron deficiency anaemia].

PMID- 28506759
TI  - Complement C1q is hydroxylated by collagen prolyl 4 hydroxylase and is sensitive
      to off-target inhibition by prolyl hydroxylase domain inhibitors that stabilize
      hypoxia-inducible factor.
AB  - Complement C1q is part of the C1 macromolecular complex that mediates the
      classical complement activation pathway: a major arm of innate immune defense.
      C1q is composed of A, B, and C chains that require post-translational prolyl 4
      hydroxylation of their N-terminal collagen-like domain to enable the formation of
      the functional triple helical multimers. The prolyl 4-hydroxylase(s) that
      hydroxylate C1q have not previously been identified. Recognized prolyl 4
      hydroxylases include collagen prolyl-4-hydroxylases (CP4H) and the more recently
      described prolyl hydroxylase domain (PHD) enzymes that act as oxygen sensors
      regulating hypoxia-inducible factor (HIF). We show that several small-molecule
      prolyl hydroxylase inhibitors that activate HIF also potently suppress C1q
      secretion by human macrophages. However, reducing oxygenation to a level that
      activates HIF does not compromise C1q hydroxylation. In vitro studies showed that
      a C1q A chain peptide is not a substrate for PHD2 but is a substrate for CP4H1.
      Circulating levels of C1q did not differ between wild-type mice or mice with
      genetic deficits in PHD enzymes, but were reduced by prolyl hydroxylase
      inhibitors. Thus, C1q is hydroxylated by CP4H, but not the structurally related
      PHD hydroxylases. Hence, reduction of C1q levels may be an important off-target
      side effect of small molecule PHD inhibitors developed as treatments for renal
      anemia.

PMID- 28506758
TI  - Decreased homodimerization and increased TIMP-1 complexation of uteroplacental
      and uterine arterial matrix metalloproteinase-9 during hypertension-in-pregnancy.
AB  - Preeclampsia is a complication of pregnancy manifested as hypertension-in
      pregnancy (HTN-Preg) and often intrauterine growth restriction (IUGR). Placental
      ischemia could be an initiating event, but the molecular mechanisms are unclear.
      To test the hypothesis that dimerization of matrix metalloproteinases (MMPs)
      plays a role in HTN-Preg and IUGR, the levels/activity of MMP-9, tissue inhibitor
      of metalloproteinase (TIMP-1), and their dimerization forms were measured in the
      placenta, uterus, and uterine artery of normal pregnant (Preg) rats and a rat
      model of reduced uteroplacental perfusion pressure (RUPP). Consistent with our
      previous report, blood pressure (BP) was higher, pup weight was lower, and
      gelatin zymography showed different gelatinolytic activity for pro-MMP-9, MMP-9,
      pro-MMP-2 and MMP-2 in RUPP vs Preg rats. Careful examination of the zymograms
      showed additional bands at 200 and 135kDa. Western blots with MMP-9 antibody
      suggested that the 200kDa band was a MMP-9 homodimer. Western blots with TIMP-1
      antibody as well as reverse zymography suggested that the 135kDa band was a MMP
      9/TIMP-1 complex. The protein levels and gelatinase activity of MMP-9 homodimer
      were decreased while MMP-9/TIMP-1 complex was increased in placenta, uterus and
      uterine artery of RUPP vs Preg rats. The epidermal growth factor (EGF) receptor
      blocker erlotinib and protein kinase C (PKC) inhibitor bisindolylmaleimide
      decreased MMP-9 homodimer and increased MMP-9/TIMP-1 complex in placenta, uterus
      and uterine artery of Preg rats. EGF and the PKC activator phorbol-12,13
      dibutyrate (PDBu) reversed the decreases in MMP-9 homodimer and the increases in
      MMP-9/TIMP-1 complex in tissues of RUPP rats. Thus, the increased BP and
      decreased pup weight in placental ischemia model of HTN-Preg are associated with
      a decrease in MMP-9 homodimer and an increase in MMP-9/TIMP-1 complex in
      placenta, uterus, and uterine artery, which together would cause a net decrease
      in MMP-9 activity and reduce uteroplacental and vascular remodeling in the
      setting of HTN-Preg and IUGR. Enhancing EGFR/PKC signaling may reverse the MMP-9
      unfavorable dimerization patterns and thereby promote uteroplacental and vascular
      remodeling in preeclampsia.

PMID- 28506761
TI  - The decline in kidney function with chromium exposure is exacerbated with co
      exposure to lead and cadmium.
AB  - Environmental factors contribute significantly to the pathogenesis of chronic
      kidney disease. However, these factors, and particularly the toxic effects of
      heavy metals, have not been completely evaluated. Chromium is a widespread
      industrial contaminant that has been linked to nephrotoxicity in animal and
      occupational population studies. Nevertheless, its role in population renal
      health and its potential interactions with other nephrotoxic metals, such as lead
      and cadmium, remain unknown. We assessed the association between exposure to
      chromium, lead, and cadmium with renal function using estimated glomerular
      filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19-84 years
      from the National Nutrition and Health Survey in Taiwan (2005-2008). Doubling of
      urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m2 (95%
      confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after
      adjusting for age, sex, body mass index, hypertension, diabetes, cigarette
      smoking, sodium intake, education, urinary volume, and other metals. For those in
      the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73
      m2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m2 (-17.01, 
      5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a
      significant and independent association between chromium exposure and decreased
      renal function. Furthermore, co-exposure to chromium with lead and cadmium is
      potentially associated with additional decline in the glomerular filtration rate
      in Taiwanese adults.

PMID- 28506760
TI  - Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal
      survival, frequency of relapse, and outcomes compared to single-seropositive
      patients.
AB  - Co-presentation with both ANCA and anti-GBM antibodies is thought to be
      relatively rare. Current studies of such 'double-positive' cases report small
      numbers and variable outcomes. To study this further we retrospectively analyzed
      clinical features and long-term outcomes of a large cohort of 568 contemporary
      patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and
      37 double-positive patients with ANCA and anti-GBM disease from four European
      centers. Double-positive patients shared characteristics of ANCA-associated
      vasculitis (AAV), such as older age distribution and longer symptom duration
      before diagnosis, and features of anti-GBM disease, such as severe renal disease
      and high frequency of lung hemorrhage at presentation. Despite having more
      evidence of chronic injury on renal biopsy compared to patients with anti-GBM
      disease, double-positive patients had a greater tendency to recover from being
      dialysis-dependent after treatment and had intermediate long-term renal survival
      compared to the single-positive patients. However, overall patient survival was
      similar in all three groups. Predictors of poor patient survival included
      advanced age, severe renal failure, and lung hemorrhage at presentation. No
      single-positive anti-GBM patients experienced disease relapse, whereas
      approximately half of surviving patients with AAV and double-positive patients
      had recurrent disease during a median follow-up of 4.8 years. Thus, double
      positive patients have a truly hybrid disease phenotype, requiring aggressive
      early treatment for anti-GBM disease, and careful long-term follow-up and
      consideration for maintenance immunosuppression for AAV. Since double-positivity
      appears common, further work is required to define the underlying mechanisms of
      this association and define optimum treatment strategies.

PMID- 28506763
TI  - Neonatal hyperoxia disrupts the intestinal barrier and impairs intestinal
      function in rats.
AB  - Animal studies have demonstrated that neonatal hyperoxia injures the distal small
      intestine and disrupts the intestinal barrier. This study evaluated the effects
      of brief hyperoxia exposure on intestinal function in newborn rats. Newborn
      Sprague-Dawley rat pups were exposed to room air or normobaric hyperoxia (85% O2)
      for 1week. The rats were euthanized on Postnatal Day 7, and their terminal ilea
      and sera were collected for histological analyses and intestinal permeability
      measurements, respectively. Bacterial translocation to the liver and spleen under
      aerobic and anaerobic conditions was determined. The expression and localization
      of epithelial injury markers [intestinal fatty acid binding protein (I-FABP)],
      intestinal barrier proteins [occludin and zonula occludens (ZO)-1], and
      inflammation biomarkers [Toll-like receptor 4 (TLR4) and nuclear factor-kappaB
      (NF-kappaB)] were analyzed through immunofluorescence staining. The body weight
      at birth was comparable between the two groups. On Postnatal Day 7, the rats in
      the hyperoxic group exhibited significantly lower body weights, higher intestinal
      injury scores, lower numbers of goblet cells, higher I-FABP expression, lower
      occludin and ZO-1 expression, higher TLR4 and NF-kappaB expression, and higher
      intestinal permeability and bacterial translocation than did those in the room
      air group. The rats reared in O2-enriched air displayed indistinct tight junction
      with widening of the paracellular spaces. Hyperoxia exposure injured the distal
      small intestine, disrupted the intestinal barrier, and impaired intestinal
      function in newborn rats. Hyperoxia-induced intestinal injury may be attributable
      to increased activity of the TLR4/NF-kappaB pathway during the postnatal period.

PMID- 28506762
TI  - The nuclear phosphatase SCP4 regulates FoxO transcription factors during muscle
      wasting in chronic kidney disease.
AB  - Chronic kidney disease (CKD) and related inflammatory responses stimulate protein
      energy wasting, a complication causing loss of muscle mass. Primarily, muscle
      wasting results from accelerated protein degradation via autophagic/lysosomal and
      proteasomal pathways, but mechanisms regulating these proteolysis pathways remain
      unclear. Since dephosphorylation of FoxOs regulates ubiquitin/proteasome protein
      metabolism, we tested whether a novel nuclear phosphatase, the small C-terminal
      domain phosphatase (SCP) 4, regulates FoxOs signaling and, in turn, muscle
      wasting. In cultured mouse myoblast cells, SCP4 overexpression stimulated
      proteolysis, while knockdown of SCP4 prevented the proteolysis stimulated by
      inflammatory cytokines. SCP4 overexpression led to nuclear accumulation of
      FoxO1/3a followed by increased expression of catabolic factors including
      myostatin, Atrogin-1, and MuRF-1, and induction of lysosomal-mediated
      proteolysis. Treatment of C2C12 myotubes with proinflammatory cytokines
      stimulated SCP4 expression in an NF-kappaB-dependent manner. In skeletal muscle
      of mice with CKD, SCP4 expression was up-regulated. Similarly, in skeletal muscle
      of patients with CKD, SCP4 expression was significantly increased. Knockdown of
      SCP4 significantly suppressed FoxO1/3a-mediated expression of Atrogin-1 and MuRF
      1 and prevented muscle wasting in mice with CKD. Thus, SCP4 is a novel regulator
      of FoxO transcription factors and promotes cellular proteolysis. Hence, targeting
      SCP4 may prevent muscle wasting in CKD and possibly other catabolic conditions.

PMID- 28506764
TI  - Specific localization of LC3B in autophagosome: A correlative labelling study
      with nanoparticle in oral squamous cell carcinoma.

PMID- 28506765
TI  - Augmenter of liver regeneration (ALR) exhibits a dual signaling impact on hepatic
      acute-phase response.
AB  - The acute-phase response (APR) is an inflammatory process triggered mainly by IL
      6 in response to neoplasm, tissue injury, infection or inflammation. Signaling of
      IL-6 is transduced by activating STAT3 which rapidly results in production of
      acute-phase proteins (APPs) such as fibrinogen beta (FGB) and haptoglobin (HP).
      Augmenter of liver regeneration (ALR), a hepatotrophic factor supporting liver
      regeneration, was reported to be upregulated after liver damage. In this study we
      analyzed the role of ALR for IL-6 signaling and APR. Thus, we investigated the
      expression and release of APPs in human liver cells under conditions of increased
      exogenous or endogenous ALR. HepG2 cells and ALR-reexpressing HepG2 cells were
      treated with IL-6 in the presence or absence of exogenous ALR for different time
      points. The mRNA expression and release of both FGB and HP were measured by RT
      PCR and ELISA. We found that exogenously applied ALR attenuated the IL-6-induced
      mRNA expression and protein secretion of both FGB and HP. In contrast, IL-6
      stimulation in HepG2 cells which re-express ALR, revealed elevated APR shown by
      increased mRNA expression and secretion of FGB and HP. Furthermore, we found that
      ALR-mediated regulation of IL-6-induced APP production is accompanied by altered
      STAT3 activity. While exogenous ALR reduced the IL-6-induced phosphorylation of
      STAT3, endogenous ALR enhanced STAT3 activity in liver cells. In conclusion, ALR,
      dependent on its localization, changes APR at least in part, by modifying STAT3
      activation. This study shows a dual signaling of ALR and suggests that ALR is
      pivotal for the regulation of APR, a crucial event in liver injury and
      regeneration.

PMID- 28506766
TI  - Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation,
      migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by
      targeting MTA1.
AB  - OBJECTIVE: This study aims to explore effects of miR-183 on epithelial
      mesenchymal transition (EMT) and invasion by targeting MTA1 in human pancreatic
      cancer (PC) cells. METHODS: Totally, 108 PC patients admitted in Wenzhou Central
      Hospital and Wenzhou People's Hospital, The Dingli Clinical Institute of Wenzhou
      Medical University from March 2010 to March 2014 were enrolled. qRT-PCR and
      immunohistochemistry were applied to examine expression of MTA1 mRNA and protein.
      Samples were divided into 6 groups: blank, NC, miR-183 mimics, miR-183
      inhibitors, MTA1-siRNA and miR-183 inhibitors +MTA1-siRNA groups. CCK8 method was
      employed for determining cell proliferation rate, flow cytometry for cell
      apoptosis rate, scratch test for cell migration and Transwell assay for cell
      invasion. qRT-PCR and Western blotting were used to determine expression of MTA1,
      E-cadherin and Vimentin mRNA and protein. RESULTS: Positive expression rate of
      MTA1 was upregulated in PC tissues, and expression of miR-183 and MTA1 was
      associated with differentiation, migration, tumor size, TNM. The miR-183 mimics
      and MTA1-siRNA groups showed a decrease in proliferation, migration and invasion,
      whereas increased apoptosis, in comparison with blank and NC groups, as
      expression of MTA1 and Vimentin mRNA and protein were reduced, expression of E
      cadherin mRNA and protein was elevated. Compared to blank and NC groups, the miR
      183 inhibitors group exhibited enhanced proliferation, migration and invasion and
      inhibited apoptosis; increased expressions of MTA1 and Vimentin mRNA and protein
      and decreased expressions of E-cadherin mRNA and protein. CONCLUSION: Our study
      supported that miR-183 could repress EMT and invasion of human PC cells through
      inhibition of MTA1 expression.

PMID- 28506768
TI  - Low expression of long non-coding RNA GAS5 is associated with poor prognosis of
      patients with thyroid cancer.
AB  - The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in
      the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A
      total of 212 patients with TC and 61 patients with benign thyroid tumor were
      enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR)
      was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues.
      All TC patients were categorized into high-risk and low-risk groups according to
      the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was
      conducted in order to determine the disease free survival (DFS) rates and overall
      survival (OS) rates. The associations between lncRNA GAS5 expression and
      prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and
      the Cox regression models. There was a decrease in the lncRNA GAS5 expression in
      TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5
      showed significant association with tumor node metastasis (TNM) staging, lymph
      node metastasis and the multiple cancer foci of TC. AMES high-risk patients
      showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk
      patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5
      expression than low-risk patients. The survival rate of TC patients with high
      lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5
      expression during the DFS and OS periods. Cox regression analysis indicated that
      lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer
      foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5
      may be closely related to the diagnosis and prognosis of TC.

PMID- 28506767
TI  - Mig-6 is down-regulated in HCC and inhibits the proliferation of HCC cells via
      the P-ERK/Cyclin D1 pathway.
AB  - The ablation of Mig-6 has been shown to induce tumor formation in various
      tissues. However, the relationships between Mig-6 expression, clinical
      pathological factors, and prognosis have not been clarified in hepatocellular
      carcinoma (HCC), and the mechanism by which Mig-6 regulates the proliferation of
      HCC cells has not been reported. In this study, we investigated the clinical
      significance of the loss of Mig-6 expression in HCC and the mechanism underlying
      the inhibition of cell proliferation by Mig-6. The down-regulation of Mig-6
      correlated significantly with large tumors, a more advanced BCLC stage, and a
      more advanced TNM stage, and low Mig-6 expression predicted significantly reduced
      survival. Low Mig-6 expression and high Cyclin D1 expression were independent
      predictors for survival. The overexpression of Mig-6 led to significant G1 arrest
      and growth inhibition in HCC cells, possibly through the inhibition P-ERK and
      Cyclin D1. These results indicate that Mig-6 expression is low in HCC, which
      predicts a poor prognosis. Mig-6 may regulate cell proliferation and the cell
      cycle through the P-ERK/Cyclin D1 pathway.

PMID- 28506769
TI  - Molecular biomarkers for an early diagnosis, effective treatment and prognosis of
      colorectal cancer: Current updates.
AB  - Colorectal cancer (CRC) is the third most prevalent cancer in the world.
      Globally, it has been estimated that about 1.4 million new cases of colorectal
      cancer are diagnosed every year. CRC is a multifactorial disease that arises due
      to genetics as well as epigenetic alterations in a number of oncogenes, tumor
      suppressor genes, mismatch repair genes, as well as cell cycle regulating genes
      in colon mucosal cells. These molecular alterations have been considered as
      potential CRC biomarkers because they can provide the physicians with diagnostic,
      prognostic and treatment response information. The goal is to identify relevant,
      cheap and applicable biomarkers that contribute to patient management decisions,
      resulting in direct benefits to patients. In this review, we will outline the
      most currently available and developing tumor tools, and blood molecular
      biomarkers. Also, we will illustrate their diagnostic, therapeutic and prognostic
      applications.

PMID- 28506770
TI  - Prognostic role of telomere length in malignancies: A meta-analysis and meta
      regression.
AB  - Telomere length (TL) has been associated with several health conditions including
      cancer. To quantify the effect of TL on outcomes in malignancies and explore the
      role of type of TL measurement we conducted a librarian-led systematic search of
      electronic databases identified publications exploring the prognostic role of TL
      on cancer outcomes. Overall survival (OS) was the primary outcome measure while
      other time-to-event endpoints were secondary outcomes. Data from studies
      reporting a hazard ratio (HR) with 95% confidence interval (CI) and/or p-value
      were pooled in a meta-analysis. HRs were weighted by generic inverse variance and
      computed by random effects modeling. All statistical tests were two-sided. Sixty
      one studies comprising a total of 14,720 patients were included of which 41 (67%)
      reported OS outcomes. Overall, the pooled HR for OS was 0.88 (95%CI=0.69-1.11,
      p=0.28). Long (versus short) telomeres were associated with improved outcomes in
      chronic lymphatic leukemia (CLL) and urothelial cancer (HR=0.45, 95%CI=0.29-0.71
      and HR=0.68, 95%CI=0.46-1.00, respectively), conversely worse OS was seen with
      hepatocellular carcinoma (HR=1.90, 95%CI=1.51-2.38). Pooled HRs (95% CI) for
      progression-free survival, relapse/disease-free survival, cancer-specific
      survival, and treatment-free survival were 0.56 (0.41-0.76), 0.76 (0.53-1.10),
      0.72 (0.48-1.10), and 0.48 (0.39-0.60), respectively. There was substantial
      heterogeneity of tissues and methods used for TL measurement and no clear
      association between TL and outcome was identified in subgroups. In conclusion,
      there is inconsistent effect of TL on cancer outcomes possibly due to variable
      methods of measurement. Standardization of measurement and reporting of TL is
      warranted before the prognostic value of TL can be accurately assessed.

PMID- 28506772
TI  - Treatment of Epithelioid angiosarcoma with Topical ALA-PDT in the course of
      surgery.
AB  - BACKGROUND: Epithelioid angiosarcoma is a high grade malignancy sarcoma of soft
      tissue, which is hard to diagnose and completely excise without causing
      functional and cosmetic problems. Moreover, the high rate of recurrence is hard
      to salvage. Photodynamic therapy is a novel treatment protocol which can
      selectively destroy tumor cell with good functional and cosmetic outcomes.
      METHODS: This is a case about a 81 years old patient with Epithelioid
      angiosarcoma in the right medial angle of eye, which received surgery and ALA
      photodynamic therapy. RESULTS: There is no recurrence in one year after treatment
      of surgery and photodynamic therapy in the course of surgery. CONCLUSIONS:
      Excision combined with photodynamic therapy during operation is a promising
      strategy towards tumors which are hard to resect thoroughly and have a high risk
      of recurrence.

PMID- 28506771
TI  - 15d-PGJ2 as an endoplasmic reticulum stress manipulator in multiple myeloma in
      vitro and in vivo.
AB  - Multiple myeloma (MM) is characterised by intense protein folding and,
      consequently endoplasmic reticulum (ER) stress. The prostaglandin 15d-PGJ2 is
      able to raise oxidative stress levels within the cell and potentially trigger
      cell death. The aim of this study was to evaluate the antineoplastic effect of
      15d-PGJ2 on MM in vitro and in vivo via ER and oxidative stress pathways. MM.1R
      and MM.1S cell lines were treated with 15d-PGJ2 at 1-10MUM and evaluated with
      regard to proliferation, mRNA expression of PRDX1, PRDX4, GRP78, GRP94, CHOP, BCL
      2 and BAX. Stress data was validated via oxidized glutathione assays. MM.1R cells
      were inoculated into NOD/SCID mice, which were subsequently treated daily with
      15d-PGJ2 at 4mg/kg or vehicle (control), with tumour volume being monitored for
      14days. 15d-PGJ2 reduced cell proliferation, induced cell death and apoptosis at
      5MUM and 10MUM and Stress-related genes were upregulated at the same doses.
      Oxidized glutathione levels were also increased. 15d-PGJ2 at 4mg/kg in vivo
      halted tumour growth. In conclusion, 15d-PGJ2 induced myeloma cell death via ER
      stress in vitro. 15d-PGJ2 in vivo also inhibited tumour growth.

PMID- 28506774
TI  - Immunomodulatory and protective effects of adipose tissue-derived mesenchymal
      stem cells in an allograft islet composite transplantation for experimental
      autoimmune type 1 diabetes.
AB  - BACKGROUND: Allogeneic islet transplantation could be an ideal alternative
      therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal
      Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may
      have the potential to improve the outcome of this highly immunogenic transplant.
      METHODS: Syngenic AT-MSCs along with allograft islets embedded in hydrogelic
      composite and transplanted intraperitoneally in Streptozotocin (STZ) induced
      diabetic C57BL/6 mice. RESULTS: In vitro experiments of co-imbedded islets and AT
      MSCs in a hydrogel revealed AT-MSCs are able to significantly increase insulin
      secretion. During a 32 days of post-transplant period, blood glucose monitoring
      showed a decrease from over 400mg/dl to less than 150mg/dl and at the end of 32
      days, mice have been dissected and assessed. Graft histopathology demonstrated
      that hydrogel makes an artificial immune isolation site and AT-MSCs contribute
      greatly to the reduction of the immune cells infiltration. Analyses of
      mononuclear cells isolated from Mesenteric Lymph Nodes (MLNs) and spleen showed
      that AT-MSCs co-transplanted with allograft decreased pro-inflammatory cytokines
      and increased regulatory cytokines (for both MLNs and spleen) and regulatory T
      cells (Treg) population (only for MLNs). In addition, real time-PCR assays
      revealed that transcript levels of IDO, iNOS, and PDX1, significantly increased
      in allograft islets in the presence of AT-MSCs. CONCLUSIONS: according to
      results, this investigation indicates that AT-MSCs can be regarded as promising
      complementary candidates for engineered-cell therapy using hydrogel composites in
      islet transplantation.

PMID- 28506773
TI  - Antimicrobial photodynamic therapy with photosensitizer in ethanol improves
      oxidative status and gingival collagen in a short-term in periodontitis.
AB  - BACKGROUND: This study evaluated the antimicrobial photodynamic therapy (aPDT)
      effects using the methylene blue (MB) in ethanol 20% on systemic oxidative status
      and collagen content from gingiva of rats with periodontitis. METHODS: Rats were
      divided into five experimental groups: NC (negative control; no periodontitis);
      PC (positive control; periodontitis without any treatment); SRP (periodontitis
      and scaling and root planing), aPDT I (periodontitis and SRP+aPDT+MB solubilized
      in water), and aPDT II (periodontitis and SRP+aPDT+MB solubilized in ethanol
      20%). After 7days of removal of the ligature, the periodontal treatments were
      performed. At 7/15/30days, gingival tissue was removed for morphometric analysis.
      The erythrocytes were used to evaluate systemic oxidative status. RESULTS: PC
      group showed higher lipoperoxidation levels at 7/15/30days. aPDT indicated a
      protective influence in erythrocytes at 15days observed by the elevation in
      levels of systemic antioxidant defense. aPDT II group was the only one that
      restored the total collagen area in 15days, and recovered the type I collagen
      area at the same time point. CONCLUSIONS: aPDT as an adjunct to the SRP can
      induce the systemic protective response against oxidative stress periodontitis
      induced and recover the gingival collagen, thus promoting the healing
      periodontal, particularly when the MB is dissolved in ethanol 20%.

PMID- 28506775
TI  - Supervised or Unsupervised Rehabilitation After Total Hip Replacement Provides
      Similar Improvements for Patients: A Randomized Controlled Trial.
AB  - OBJECTIVE: To determine whether patients do better with unsupervised (home-based)
      physiotherapy or in an outpatient setting. SETTING: Acute care public hospital in
      the region, supporting a population of ~540,000. DESIGN: Single-blind randomized
      controlled trial. PARTICIPANTS: Adult patients (N=98) after unilateral elective
      total hip replacement (THR) were randomly assigned to a supervised (center-based)
      exercise (n=56) or a unsupervised (home-based) exercise (n=42) program and
      followed for 6 months postsurgery. INTERVENTIONS: The supervised group attended a
      4-week outpatient rehabilitation program supervised by a physiotherapist. The
      unsupervised group was given written and pictorial instructions to perform
      rehabilitation independently at home. MAIN OUTCOME MEASURES: Western Ontario and
      McMaster Universities Osteoarthritis Index; Short-Form 36-item Health
      Questionnaire (SF-36) mental and physical component summary measures; University
      of California, Los Angeles activity scale; and timed Up and Go test. RESULTS:
      There were no differences between the groups for any measure. The overall
      differences between the adjusted means were as follows: Western Ontario and
      McMaster Universities Osteoarthritis Index, 0.50 (95% confidence interval [CI], 
      6.8 to 5.7); SF-36 physical component summary, 0.8 (95% CI, -6.5 to 8.1); SF-36
      mental component summary, 1.7 (95% CI, -4.1 to 7.4); University of California,
      Los Angeles activity scale, 0.3 (95% CI, 5.2 to 6.1); and timed Up and Go test, 0
      seconds (95% CI, -1.4 to 1.3s). CONCLUSIONS: The results demonstrated that
      outcomes in response to rehabilitation after THR are clinically and statistically
      similar whether the program was supervised or not. The results suggest that early
      rehabilitation programs can be effectively delivered unsupervised in the home to
      low-risk patients discharged home after THR. However, the relative effect of late
      stage rehabilitation was not tested.

PMID- 28506777
TI  - Beyond Negative Pain-Related Psychological Factors: Resilience Is Related to
      Lower Pain Affect in Healthy Adults.
AB  - : Resilience, a characteristic that enhances adaptation in response to stressful
      events, is a positive psychological factor that can predict and modulate health
      outcomes. However, resilience is rarely considered in pain research. Conversely,
      negative psychological factors (eg, anxiety, depression) are known to be related
      to the affective dimension of pain. It is critical to understand all potential
      psychological drivers of pain affect, a prominent component of chronic pain. We
      tested the hypothesis that higher resilience is associated with lower pain
      affect, above and beyond the predictive value of negative psychological factors.
      Healthy adults underwent psychophysical testing to acquire ratings of heat pain
      intensity and unpleasantness and completed the Resilience Scale, the State-Trait
      Anxiety Inventory (trait form), Beck Depression Inventory, Pain Catastrophizing
      Scale, and the Pain Vigilance and Attention Questionnaire. Multiple regression
      modeling (n = 68) showed resilience to be a negatively associated with pain
      affect (unpleasantness). Furthermore, in individuals with higher anxiety scores,
      resilience was protective against higher pain affect. This highlights the
      importance of resilience, a positive psychological factor, in the affective
      dimension of pain. This study is the first to assess a positive psychological
      factor and experimental pain affect, and has the potential to improve prediction
      of and treatment strategies for clinical pain. PERSPECTIVE: We report that
      resilience, a positive psychological factor, interacts with anxiety and is
      associated with heat pain affect (unpleasantness) in healthy individuals.
      Resilience may provide predictive value of chronic pain affect and treatment
      outcomes, and could be a target for behavioral therapy.

PMID- 28506778
TI  - Genetic Factors Explain the Association Between Pain Catastrophizing and Chronic
      Widespread Pain.
AB  - : This study aimed to clarify whether there are shared genetic and/or
      environmental factors explaining the strong link between pain catastrophizing
      (PC) and chronic widespread pain (CWP). Data were available for N = 1,109 female
      twins from TwinsUK. Information on self-reported CWP and PC was subject to
      variance component twin analysis. Heritabilities were 40% for PC and 77% for CWP.
      The genetic correlation between PC and CWP was .40%, whereas no evidence of an
      environmental correlation could be detected (.0). According to the best-fitting
      additive genetic, non-shared environmental (AE) Cholesky model, an additive
      genetic factor loading on PC as well as CWP, as well as an additive genetic
      factor loading on CWP alone was found. In terms of environmental influences, 2
      individual environmental factors could be identified, loading separately on PC
      and CWP. Overall, the results add to the knowledge on the nature of CWP and the
      basis of its close relationship with PC by suggesting a shared genetic
      etiological structure. The findings highlight a potential avenue for future
      research and may provide useful insight for the clinical management of pain and
      pain coping. PERSPECTIVE: Results suggest a shared genetic etiological structure
      between CWP and PC with no shared influence of environmental factors. Clinicians
      should be aware of this biological link within the context of clinical management
      of pain and pain coping.

PMID- 28506776
TI  - Mindfulness Is Associated With Treatment Response From Nonpharmacologic Exercise
      Interventions in Knee Osteoarthritis.
AB  - OBJECTIVE: To examine the association between baseline mindfulness and response
      from exercise interventions in knee osteoarthritis (OA). DESIGN: Cohort study;
      responder analysis of a clinical trial subset. SETTING: Urban tertiary care
      academic hospital. PARTICIPANTS: Participants with symptomatic, radiographic knee
      OA (N=86; mean age, 60y; 74% female; 48% white). INTERVENTIONS: Twelve weeks
      (twice per week) of Tai Chi or physical therapy exercise. MAIN OUTCOME MEASURES:
      Treatment response was defined using Osteoarthritis Research Society
      International criteria indicating meaningful improvements in the Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC function, or
      Patient Global Assessment scores. At baseline, participants completed the Five
      Facet Mindfulness Questionnaire (mean total score, 142+/-17) and were grouped
      into 3 categories of total mindfulness: higher, medium, or lower. Relative risk
      (RR) ratios were used to compare treatment response across groups. RESULTS:
      Participants with higher total mindfulness were 38% (95% confidence interval
      [CI], 1.05-1.83) more likely to meet responder criteria than those with lower
      mindfulness. We found no significant difference between medium and lower
      mindfulness groups (RR=1.0; 95% CI, 0.69-1.44). Among the 5 mindfulness facets,
      medium acting-with-awareness was 46% (95% CI, 1.09-1.96) more likely to respond
      than lower acting-with-awareness, and higher acting-with-awareness was 34% more
      likely to respond, but this did not reach significance (95% CI, 0.97-1.86).
      CONCLUSIONS: In this study, higher mindfulness, primarily driven by its acting
      with-awareness facet, was significantly associated with a greater likelihood of
      response to nonpharmacologic exercise interventions in knee OA. This suggests
      that mindfulness-cultivating interventions may increase the likelihood of
      response from exercise.

PMID- 28506779
TI  - This Gut Ain't Big Enough for Both of Us. Or Is It? Helminth-Microbiota
      Interactions in Veterinary Species.
AB  - Gastrointestinal helminth parasites share their habitat with a myriad of other
      organisms, that is, the commensal microbiota. Increasing evidence, particularly
      in humans and rodent models of helminth infection, points towards a multitude of
      interactions occurring between parasites and the gut microbiota, with a profound
      impact on both host immunity and metabolic potential. Despite this information,
      the exploration of the effects that parasite infections exert on populations of
      commensal gut microbes of veterinary species is a field of research in its
      infancy. In this article, we summarise studies that have contributed to current
      knowledge of helminth-microbiota interactions in species of veterinary interest,
      and identify possible avenues for future research in this area, which could
      include the exploitation of such relationships to improve parasite control and
      delay or prevent the development of anthelmintic resistance.

PMID- 28506780
TI  - A novel approach for regional anaesthesia of the auricular region in horses: an
      anatomic and imaging study.
AB  - OBJECTIVE: To investigate the anatomy of the ear innervation in horses and
      develop a new approach for the block of the internal and external pinna and
      acoustic meatus. STUDY DESIGN: Prospective, descriptive, cadaveric study.
      ANIMALS: A total of 25 heads and necks from horse cadavers. METHODS: Phase I:
      anatomical dissection and dye deposition on 19 heads. With the head positioned in
      lateral recumbency, 10 mL methylene blue (1:1 sterile water) for the internal
      auricular and 2 mL for the great auricular nerve block were injected in 21 ears
      (seven left, 10 right and two bilaterally). The anatomy of all the ears
      (bilaterally) and the accuracy of dye deposition (successful nerve staining
      defined as > 2 cm) was assessed following dissection. Occurrence of intraparotid,
      intravascular, or intraneural injection was recorded. Phase II: the same
      technique and volumes were applied, bilaterally, using a lidocaine 2%:iohexol
      solution mixture (3:1) in six different cadavers. Computed tomography was
      performed and the needle position and spread of the mixture evaluated and
      recorded. RESULTS: Phase I: Inter- and intraindividual differences were found in
      the anatomy of the great auricular nerve, but not in the internal and lateral
      auricular nerve branches and the caudal auricular nerve. No auriculotemporal
      nerve was found. Nerve staining was successful in 95% of the cases for the great
      auricular nerve, 85% of the cases for the internal auricular nerve, and 100% of
      the cases for the lateral auricular branch and caudal auricular nerve. Failure
      was observed in horses with abundant periauricular fat. No intravascular,
      intraparotid or intraneural injections occurred. Phase II: A 100% success rate
      was recorded from computed tomography images. CONCLUSIONS AND CLINICAL RELEVANCE:
      The described approach seems suitable for blockade of the sensory innervation of
      the equine ear.

PMID- 28506781
TI  - Implementation of quality management for clinical bacteriology in low-resource
      settings.
AB  - BACKGROUND: The declining trend of malaria and the recent prioritization of
      containment of antimicrobial resistance have created a momentum to implement
      clinical bacteriology in low-resource settings. Successful implementation relies
      on guidance by a quality management system (QMS). Over the past decade
      international initiatives were launched towards implementation of QMS in
      HIV/AIDS, tuberculosis and malaria. AIMS: To describe the progress towards
      accreditation of medical laboratories and to identify the challenges and best
      practices for implementation of QMS in clinical bacteriology in low-resource
      settings. SOURCES: Published literature, online reports and websites related to
      the implementation of laboratory QMS, accreditation of medical laboratories and
      initiatives for containment of antimicrobial resistance. CONTENT: Apart from the
      limitations of infrastructure, equipment, consumables and staff, QMS are
      challenged with the complexity of clinical bacteriology and the healthcare
      context in low-resource settings (small-scale laboratories, attitudes and
      perception of staff, absence of laboratory information systems). Likewise, most
      international initiatives addressing laboratory health strengthening have focused
      on public health and outbreak management rather than on hospital based patient
      care. Best practices to implement quality-assured clinical bacteriology in low
      resource settings include alignment with national regulations and public health
      reference laboratories, participating in external quality assurance programmes,
      support from the hospital's management, starting with attainable projects,
      conducting error review and daily bench-side supervision, looking for locally
      adapted solutions, stimulating ownership and extending existing training
      programmes to clinical bacteriology. IMPLICATIONS: The implementation of QMS in
      clinical bacteriology in hospital settings will ultimately boost a culture of
      quality to all sectors of healthcare in low-resource settings.

PMID- 28506782
TI  - The misleading effect of serum galactomannan testing in high-risk haematology
      patients receiving prophylaxis with micafungin.
AB  - OBJECTIVES: To investigate the performance of the routine serum galactomannan
      (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk
      haematology patients receiving prophylaxis with micafungin. METHODS:
      Retrospective study including all haematological patients who received
      prophylaxis with micafungin during high-risk IA episodes (neutropenic patients
      after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome;
      allogeneic haematopoietic stem-cell transplantation during early neutropenic
      phase or graft-versus-host disease requiring high prednisone doses) and for whom
      at least one sGM result was available. Episodes were classified as follows: true
      positive (positive GM in the context of IA), false-positive (positive GM result
      in patients who had no evidence of IA), true-negative (negative GM test results
      and no IA), or false-negative (negative GM test in the context of IA). Non
      evaluable patients were excluded. RESULTS: Among 146 evaluable episodes, four
      were true-positive in the context of probable breakthrough IA (incidence of
      breakthrough IA, 2.7%); 111/146 high-risk episodes (76%) were considered true
      negative and 31/146 (21.2%) were considered false-positive. No false-negative
      episodes were detected. All but one of the false-positive episodes were detected
      in surveillance GM tests, leading to high-resolution CT scans in eight cases
      (8/31; 25.8%), all of which were negative. The positive predictive and negative
      predictive values of sGM for surveillance and diagnostic approaches were 3.2%
      (1/31) and 100% (110/110) and 75% (3/4) and 100% (1/1), respectively.
      CONCLUSIONS: Surveillance of asymptomatic patients receiving prophylaxis with
      micafungin using sGM is unnecessary, because the results are either negative or
      false-positive. However, sGM remains useful in the diagnosis of breakthrough IA
      in symptomatic patients during prophylaxis.

PMID- 28506783
TI  - The professional status of infectious disease physicians in China: a nationwide
      cross-sectional survey.
AB  - OBJECTIVES: The evolution of infectious diseases (IDs) poses a challenge to many
      ID physicians, who must either adapt or transition to another career track. This
      national cross-sectional study assessed the current working conditions and
      problems faced by ID professionals in China. METHODS: A national questionnaire
      survey of ID physicians and their facilities throughout China was performed in
      May-June 2016 using stratified random sampling. RESULTS: A total of 156/300
      (52.0%) ID departments and 1071/2250 (47.6%) physicians from 21 provinces
      participated in the survey. Overall, 151 (96.2%) of 156 hospitals had ID wards
      and 141 (90.4%) provided outpatient consultations. The average number of ID
      physicians per department was 10.32 +/- 6.57. The ratio of patient beds to
      doctors was 5: 1, and the ratio of patient beds to nurses was 5: 1.85. Training
      in IDs was available in 126 (80.8%), and ID research was performed in 108
      (69.2%), of the 156 departments. The main service provided by ID physicians was
      the management of legally notifiable communicable diseases. The annual income of
      942 (88.0%) of the 1071 physicians was below $15 000. Of these physicians, 870
      (81.2%) felt high or very high pressure in their work, whereas only 514 (48.0%)
      were satisfied or very satisfied with their jobs. CONCLUSIONS: The limited
      medical service provided by ID physicians is poorly aligned with current
      healthcare demands. Moreover, the heavy workloads, high stress, poor compensation
      and limited career prospects for ID physicians in China impede the continued
      development of specialists and places them in a career dilemma. ID physicians
      should work to develop and diversify the field and to enhance their capacities by
      learning new technologies and collaborating with other medical disciplines.

PMID- 28506784
TI  - Healthcare personnel intestinal colonization with multidrug-resistant organisms.
AB  - OBJECTIVES: This study aims to assess the association between patient contact and
      intestinal carriage of multidrug-resistant organisms (MDRO) by sampling
      healthcare personnel (HCP) and staff without patient contact. METHODS: For this
      observational study, we recruited 400 HCP who worked in our 200-bed research
      hospital and 400 individuals without patient contact between November 2013 and
      February 2015. Participants submitted two self-collected perirectal swabs and a
      questionnaire. Swabs were processed for multidrug-resistant Gram-negative
      bacteria and vancomycin-resistant enterococci (VRE). Questionnaires explored
      occupational and personal risk factors for MDRO carriage. RESULTS: Among 800
      participants, 94.4% (755/800) submitted at least one swab, and 91.4% (731/800)
      also submitted questionnaires. Extended spectrum beta-lactamase-producing
      organisms were recovered from 3.4% (26/755) of participants, and only one
      carbapenemase-producing organism was recovered. No VRE were detected. The
      potential exposure of 68.9% (250/363) of HCP who reported caring for MDRO
      colonized patients did not result in a rate of MDRO carriage among HCP (4.0%;
      15/379) significantly higher than that of staff without patient contact (3.2%;
      12/376; p 0.55). CONCLUSIONS: This is the largest US study of HCP intestinal MDRO
      carriage. The low colonization rate is probably reflective of local community
      background rates, suggesting that HCP intestinal colonization plays a minor role
      in nosocomial spread of MDROs in a non-outbreak setting. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01952158.

PMID- 28506785
TI  - What can we learn from our peer reviewers.

PMID- 28506786
TI  - Diagnostic test accuracy of antigenaemia assay for PCR-proven cytomegalovirus
      infection-systematic review and meta-analysis.
AB  - OBJECTIVES: We aimed to assess diagnostic test accuracy of antigenaemia assay for
      PCR-proven cytomegalovirus (CMV) infection. METHODS: We systematically searched
      studies that provide data both on sensitivity and specificity of the CMV
      antigenaemia assay using the PCR as the reference standard. Adults, children,
      infants, individuals who were immunocompromised for any reason, symptomatic
      patients and asymptomatic individuals were all included. A hierarchical summary
      receiver operating characteristics model was used for diagnostic meta-analysis.
      Study quality was assessed by Revised Tool for the Quality Assessment of
      Diagnostic Accuracy Studies. Protocol registration identification is
      CRD42016035892. RESULTS: We identified 75 eligible articles including 9058 CMV
      PCR-positive individuals and 22 232 PCR-negative individuals. The diagnostic odds
      ratio for positive antigenaemia was 30 (95% CI 24-38, I2 = 28%) and the area
      under the hierarchical summary receiver operating characteristic curve was 0.86
      (95% CI 0.83-0.88). The summary estimates of sensitivity and specificity were
      0.65 (95% CI 0.59-0.70) and 0.94 (95% CI 0.93-0.95), respectively. The positive
      likelihood ratio of 10.9 (95% CI 8.5-14.0) suggested that a positive result from
      the antigenaemia assay greatly increased the probability of PCR-proven CMV
      infection, but a negative likelihood ratio of 0.38 (95% CI 0.32-0.44) indicated
      that a negative result led to a small decrease in the probability of PCR-proven
      CMV infection. Sensitivity and subgroup analyses replicated these results.
      CONCLUSIONS: The antigenaemia assay overlooked 35% of PCR-proven CMV infections;
      hence, a negative result of an antigenaemia assay could not rule out a CMV
      infection.

PMID- 28506788
TI  - In Reply to 'Assessing the Effect of Spironolactone on Acute Kidney Injury After
      Cardiac Surgery'.

PMID- 28506789
TI  - Assessing the Effect of Spironolactone on Acute Kidney Injury After Cardiac
      Surgery.

PMID- 28506787
TI  - Empyema thoracis caused by an optrA-positive and linezolid-intermediate
      Enterococcus faecalis strain.

PMID- 28506790
TI  - Single particle labeling of RNA virus in live cells.
AB  - Real-time and visual tracking of viral infection is crucial for elucidating the
      infectious and pathogenesis mechanisms. To track the virus successfully, an
      efficient labeling method is necessary. In this review, we first discuss the
      practical labeling techniques for virus tracking in live cells. We then describe
      the current knowledge of interactions between RNA viruses (especially influenza
      viruses, immunodeficiency viruses, and Flaviviruses) and host cellular
      structures, obtained using single particle labeling techniques combined with real
      time fluorescence microscopy. Single particle labeling provides an easy system
      for understanding the RNA virus life cycle.

PMID- 28506791
TI  - Enterovirus 71-induced has-miR-21 contributes to evasion of host immune system by
      targeting MyD88 and IRAK1.
AB  - Enterovirus71(EV71), the etiological agent of hand-foot-and-mouth disease, has
      increasingly become a public health challenge around the world. Type I
      interferons (IFNs) are an important family of cytokines that regulate innate and
      adaptive immune responses to pathogens.These pathways are tightly regulated by
      the host to prevent an inappropriate cellular response, but viruses can modulate
      these pathways to proliferate and spread. In this study, we demonstrated that
      EV71 evades the immune surveillance system to proliferate by activating microRNA
      21. We demonstrated that EV71 infection upregulates miR-21, which in turn
      suppresses EV71-triggered type I IFN production, thus promoting EV71 replication.
      Furthermore, we demonstrated that miR-21 targets the myeloid differentiation
      factor 88(MyD88) and interleukin-1 receptor-associated kinase 1(IRAK1), which are
      involved in EV71-induced type I IFN production.

PMID- 28506792
TI  - Discovery of a novel canine respiratory coronavirus support genetic recombination
      among betacoronavirus1.
AB  - Although canine respiratory coronavirus (CRCoV) is an important respiratory
      pathogen that is prevalent in many countries, only one complete genome sequence
      of CRCoV (South Korea strain K37) has been obtained to date. Genome-wide analyses
      and recombination have rarely been conducted, as small numbers of samples and
      limited genomic characterization have previously prevented further analyses.
      Herein, we report a unique CRCoV strain, denoted strain BJ232, derived from a
      CRCoV-positive dog with a mild respiratory infection. Phylogenetic analysis based
      on complete genome of all available coronaviruses consistently show that CRCoV
      BJ232 is most closely related to human coronavirus OC43 (HCoV-OC43) and BCoV,
      forming a separate clade that split off early from other Betacoronavirus 1. Based
      on the phylogenetic and SimPlot analysis we propose that CRCoV-K37 was derived
      from genetic recombination between CRCoV-BJ232 and BCoV. In detail, spike (S)
      gene of CRCoV-K37 clustered with CRCoV-BJ232. However orf1ab, membrane (M) and
      nucleocapsid (N) genes were more related to Bovine coronavirus (BCoV) than CRCoV
      B232. Molecular epidemic analysis confirmed the prevalence of CRCoV-BJ232 lineage
      around the world for a long time. Recombinant events among Betacoronavirus 1 may
      have implications for CRCoV transmissibility. All these findings provide further
      information regarding the origin of CRCoV.

PMID- 28506793
TI  - Frequency and risk-factors analysis of Escherichia coli O157:H7 in Bali-cattle.
AB  - Cattle are known as the main reservoir of zoonotic agents verocytotoxin-producing
      Escherichia coli. These bacteria are usually isolated from calves with diarrhea
      and/or mucus and blood. Tolerance of these agents to the environmental conditions
      will strengthen of their transmission among livestock. A total of 238 cattle
      fecal samples from four sub-districts in Badung, Bali were used in this study.
      Epidemiological data observed include cattle age, sex, cattle rearing system, the
      source of drinking water, weather, altitude, and type of cage floor, the
      cleanliness of cage floor, the slope of cage floor, and the level of cattle
      cleanliness. The study was initiated by culturing of samples onto eosin methylene
      blue agar, then Gram stained, and tested for indole, methyl-red, voges proskauer,
      and citrate, Potential E.coli isolates were then cultured onto sorbitol MacConkey
      agar, and further tested using O157 latex agglutination test and H7 antisera.
      Molecular identification was performed by analysis of the 16S rRNA gene, and
      epidemiological data was analyzed using STATA 12.0 software. The results showed,
      the prevalence of E. coli O157:H7 in cattle at Badung regency was 6.30% (15/238)
      covering four sub districts i.e. Petang, Abiansemal, Mengwi, and Kuta which their
      prevalence was 8.62%(5/58), 10%(6/60), 3.33%(2/60), and 3.33(2/60)%,
      respectively. The analysis of 16S rRNA gene confirmed of isolates as an E. coli
      O157:H7 strain with 99% similarities. Furthermore, the risk factors analysis
      showed that the slope of the cage floor has a highly significant effect (P<0.05)
      to the distribution of infection. Consequently, implementing this factor must be
      concerned in order to decrease of infection.

PMID- 28506794
TI  - Life-shortening Wolbachia infection reduces population growth of Aedes aegypti.
AB  - Wolbachia bacteria are being introduced into natural populations of vector
      mosquitoes, with the goal of reducing the transmission of human diseases such as
      Zika and dengue fever. The successful establishment of Wolbachia infection is
      largely dependent on the effects of Wolbachia infection to host fitness, but the
      effects of Wolbachia infection on the individual life-history traits of immature
      mosquitoes can vary. Here, the effects of life-shortening Wolbachia (wMelPop) on
      population growth of infected individuals were evaluated by measuring larval
      survival, developmental time and adult size of Aedes aegypti in intra- (infected
      or uninfected only) and inter-group (mixed with infected and uninfected) larval
      competition assays. At low larval density conditions, the population growth of
      wMelPop infected and uninfected individuals was similar. At high larval
      densities, wMelPop infected individuals had a significantly reduced population
      growth rate relative to uninfected individuals, regardless of competition type.
      We discuss the results in relation to the invasion of the wMelPop Wolbachia
      infection into naturally uninfected populations.

PMID- 28506795
TI  - Parallel ELISAs using crude soluble antigen and excretory-secretory antigen for
      improved serodiagnosis of amoebic liver abscess.
AB  - Crude soluble antigen (CSA) produced from Entamoeba histolytica trophozoite is
      conventionally used for serodiagnosis of invasive amoebiasis. However, high
      background seropositivities by CSA-assay in endemic areas complicate the
      interpretation of positive result in clinical settings. Instead, incorporating a
      second assay which indicates active or recent infection into the routine amoebic
      serology could possibly complement the limitations of CSA-assay. Hence, the
      present study aimed to evaluate the diagnostic efficacies of indirect ELISAs
      using CSA and excretory-secretory antigen (ESA) for serodiagnosis of amoebic
      liver abscess (ALA). Reference standard for diagnosis of ALA at Hospital
      Universiti Sains Malaysia is based on clinical presentation, radiological imaging
      and positive indirect haemagglutination assay (titer >=256). Five groups of human
      serum samples collected from the hospital included Group I - ALA diagnosed by the
      reference standard and pus aspirate analysis using real-time PCR (n=10), Group II
      - ALA diagnosed by the reference standard only (n=41), Group III - healthy
      control (n=45), Group IV - other diseases control (n=51) and Group V - other
      infectious diseases control (n=31). For serodiagnosis of ALA serum samples (Group
      I and II), CSA-ELISA showed sensitivities of 100% for both groups, while ESA
      ELISA showed sensitivities of 100% and 88%, respectively. For serodiagnosis of
      non-ALA serum samples (Group III, IV and V), CSA-ELISA showed specificities of
      91%, 75% and 100%, respectively; while ESA-ELISA showed specificities of 96%, 98%
      and 100%, respectively. Indirect ELISAs using CSA and ESA have shown distinct
      strength for serodiagnosis of ALA, in terms of sensitivity and specificity,
      respectively. In conclusion, parallel analysis by both assays improved the
      overall efficacies of amoebic serology as compared to either single assay.

PMID- 28506797
TI  - [Systematic proposal of fertility preservation by mature oocyte cryopreservation
      for recurrent benign ovarian tumors].
AB  - OBJECTIVES: To investigate prospectively the pattern of the follicular growth and
      to characterize the COH outcome in terms of oocyte number and maturity in
      patients with voluminous recurrent benign ovarian tumors with a high surgical
      risk of significant reduction of the ovarian follicular content. METHODS: The
      inclusion criteria were: age between 18 and 36, presence of at least one benign
      ovarian tumor (>= 5cm) with high risk of recurrence. The fertility preservation
      cycle was performed at least 3 months after the cyst surgery. The controlled
      ovarian stimulation was performed after the ovarian reserve was assessed (AMH
      measurement and sonographic antral follicle count). Triggering was performed by
      hCG when at least 3 follicles reached 18mm of diameter. Metaphase II oocytes were
      cryopreserved by the vitrification technique. RESULTS: Twenty-four women with
      dermoid, endometrioma or seromucinous cysts were included from January 2015 to
      July 2016. All of them had previous ovarian surgery. Mean AMH levels were
      15.3pmol/L. The mean number of total oocytes retrieved was 7+/-5. The mean number
      of metaphase II oocytes was 4.4+/-4. The incidence of low ovarian response was
      38%. Among the patients, 86% had less than 8 metaphase II oocytes vitrified.
      Seven patients asked for a second cycle in order to have more oocytes.
      CONCLUSION: We demonstrated the feasibility of the systematic proposal of
      fertility preservation by oocyte cryopreservation in this group of young patients
      with recurrent ovarian benign tumors. Taking into account history of previous
      surgery and high incidence of low ovarian reserve, the ovarian response under
      stimulation was frequently poor with, as consequence, low retrieved oocyte number
      per cycle. An oocyte accumulation strategy is then proposed to enhance further
      pregnancy chances.

PMID- 28506796
TI  - From head to toe: Sex and gender differences in the treatment of ischemic
      cerebral disease.
AB  - Stroke is a major cause of mortality and morbidity, particularly in the older
      ages. Women have a longer life expectancy and are more likely to experience
      stroke than men. Interestingly, the increased risk of ischemic stroke in women
      seems to be independent from age or classical cardiovascular risk factors.
      Notwithstanding the fact that stroke outcomes and survival are usually poorer in
      women, current evidence suggests that thrombolysis, antiplatelet and
      anticoagulant therapies are more beneficial in women than in men. A possible
      explanation of this paradox might be that females are often undertreated and they
      have fewer chances to be submitted to an effective and timely treatment for
      stroke than the male counterpart. The first step in the attempt to solve this
      obvious discrimination is surely to emphasize any reasons for differences in the
      therapeutic approach in relation to gender and then to denounce the lack of a
      sustainable motivation for them. In this article, we aimed to review the existing
      literature about gender-related differences on efficacy, administration and side
      effects of the most common drugs used for the treatment of ischemic stroke. The
      most striking result was the evidence that the therapeutic approach for stroke is
      often different according to patients' gender with a clear detrimental prognostic
      effect for women. A major effort is necessary to overcome this problem in order
      to ensure equal right to treatment without any sexual discrimination.

PMID- 28506799
TI  - Diffusion-weighted imaging in quiescent Crohn's disease: correlation with
      inflammatory biomarkers and video capsule endoscopy.
AB  - AIM: To investigate the role of restricted diffusion in quiescent Crohn's disease
      (CD) patients and its association with inflammatory biomarkers and endoscopic
      disease. MATERIAL AND METHODS: Fifty-two quiescent CD patients prospectively
      underwent magnetic resonance enterography (MRE) and video capsule endoscopy (VCE)
      and were tested for the inflammatory biomarkers, faecal calprotectin (FCP) and C
      reactive protein (CRP). Restricted diffusion in the distal ileum was
      qualitatively (absence/presence) and quantitatively (apparent diffusion
      coefficient [ADC]) assessed by two readers. The VCE-based Lewis score was
      calculated for the distal ileum. Restricted diffusion sensitivity and specificity
      for VCE ulcerations were assessed for patients with elevated (>100 MUg/g) or
      normal (<100 MUg/g) FCP. Receiver operating characteristic (ROC) curve was used
      to assess the ability of ADC to identify patients with concurrent VCE ulceration
      and elevated FCP. RESULTS: The sensitivity and specificity of restricted
      diffusion for patients with VCE ulceration were higher in patients with elevated
      FCP (reader 1: 71.4%, 80%, reader 2: 76.2%, 100%, respectively) compared to
      patients with normal FCP (reader 1: 46.2%, 61.5%; reader 2: 15.4%, 76.9%,
      respectively). The ADC had a high diagnostic accuracy for identifying patients
      that had concurrent VCE ulceration and elevated FCP (reader 1: AUC=0.819, reader
      2: AUC=0.832). CONCLUSION: In quiescent CD patients, the presence of restricted
      diffusion is suggestive of an active inflammation, associated with elevated FCP.
      Thus, DWI may serve as a clinical tool in the follow-up of these patients,
      implying subclinical inflammatory flares.

PMID- 28506798
TI  - Evaluation of a semi-automated software program for the identification of
      vertebral fractures in children.
AB  - AIM: To assess observer reliability and diagnostic accuracy in children, of a
      semi-automated six-point technique developed for vertebral fracture (VF)
      diagnosis in adults, which records percentage loss of vertebral body height.
      MATERIALS AND METHODS: Using a semi-automated software program, five observers
      independently assessed T4 to L4 from the lateral spine radiographs of 137
      children and adolescents for VF. A previous consensus read by three paediatric
      radiologists using a simplified algorithm-based qualitative technique (i.e., no
      software involved) served as the reference standard. RESULTS: Of a total of 1,781
      vertebrae, 1,187 (67%) were adequately visualised according to three or more
      observers. Interobserver agreement in vertebral readability for each vertebral
      level for five observers ranged from 0.05 to 0.47 (95% CI: -0.19, 0.76). Intra
      observer agreement using the intraclass correlation coefficient (ICC) ranged from
      0.25 to 0.61. The overall sensitivity and specificity were 18% (95% CI: 14-22)
      and 97% (95% CI: 97-98), respectively. CONCLUSION: In contrast to adults, the six
      point technique assessing anterior, middle, and posterior vertebral height ratios
      is neither satisfactorily reliable nor sensitive for VF diagnosis in children.
      Training of the software on paediatric images is required in order to develop a
      paediatric standard that incorporates not only specific vertebral body height
      ratios but also the age-related physiological changes in vertebral shape that
      occur throughout childhood.

PMID- 28506800
TI  - Behaviour of silver nanoparticles in simulated saliva and gastrointestinal
      fluids.
AB  - Continuously increasing application of silver nanoparticles (AgNPs) requires
      information on their safety and performance under biological conditions.
      Assessment of AgNPs in biological systems is also related to availability of
      robust toxicological methods for evaluation of toxic potential of AgNPs and
      information on their physicochemical state. Silver nanoparticles were subjected
      to action of simulated saliva, gastric and intestinal fluids, appropriately
      supplemented with digestive enzymes pepsin or pancreatin. The behaviour of AgNPs
      was determined using dynamic light scattering and transmission electron
      microscopy, and their toxicity as well as capability to induce inflammatory
      reactions were assessed using reconstructed human tissue models (EpiOral,
      EpiGingival, EpiIntestinal). The study revealed that during exposure to the
      fluids, AgNPs size and morphology changed and depended on composition and pH of
      the respective fluid. If present, the change in terms of growth of AgNPs size
      occurred immediately after contact of AgNPs with the respective fluid and
      continued with prolonged time of contact. A pilot study on reconstituted human
      tissue models revealed low toxicity and inflammatory effects of AgNPs and
      confirmed the suitability of 3-D models for toxicological studies including
      bioavailability.

PMID- 28506801
TI  - Old drug, new wrapping - A possible comeback for chloramphenicol?
AB  - The antimicrobial drug chloramphenicol (CAM) exhibits activity against resistant
      bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). However,
      its use has been limited due to its toxicity. As the threat of antibiotic
      resistance continues to grow, a promising approach might be to increase the use
      of historical antimicrobial agents that demonstrate clinical efficacy, but are
      hampered by toxicity. We therefore aimed to prepare a liposome-in-hydrogel system
      for dermal delivery of CAM. Chitosan (CS) was used as the hydrogel vehicle due to
      its antimicrobial activity and excellent biocompatibility. All critical
      preparation steps were carried out by dual centrifugation (DC). The DC-method
      proved to be fast and simple, and organic solvents were avoided in all processing
      steps. Liposomes with high drug entrapment (49-56%), low polydispersity and a
      size of approximately 120nm were produced. Mixing of liposomes into CS-hydrogel
      by DC produced a homogenous liposomes-in-hydrogel system. Bioadhesive properties
      were good and comparable to plain CS-hydrogel formulations. Ex vivo permeation
      studies using pig skin indicated a sustained release of CAM and limited skin
      permeation. The in vitro antimicrobial activity of CAM in the new liposome-in
      hydrogel formulation was similar or better as compared to CAM in solution. Thus,
      the new formulation was considered highly promising.

PMID- 28506802
TI  - Stealth magnetic nanocarriers of siRNA as platform for breast cancer
      theranostics.
AB  - The endogenous mechanism of RNA interference is more and more used in research to
      obtain specific down-regulation of gene expression in diseases such as breast
      cancer. Currently, despite the new fields of study open up by RNA interference,
      the rapid degradation of siRNA by nucleases and their negative charges prevent
      them from crossing cell membranes. To overcome these limitations,
      superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising
      alternative for nucleic acid delivery. Previously, we reported the magnetic siRNA
      nanovectors (MSN) formulation using electrostatic assembly of (1) SPIONs, also
      able to act as contrast agents for magnetic resonance imaging (MRI), (2) siRNA
      and (3) chitosan aiming at their protection and enhancing their transfection
      efficacy. However, these nanoparticles displayed low stability in biological
      suspensions and inefficient transfection of active siRNA. This work aimed at
      upgrading MSN to Stealth MSN (S-MSN) by adding a polyethylene glycol coating to
      ensure colloidal stability and stealth properties. Furthermore, another polymer
      (poly-L-arginine) was added for efficient siRNA transfection and the quantitative
      composition of the formulation was adapted for biological purposes. Results
      showed that S-MSN provide high siRNA complexation and protection against
      enzymatic degradation. Green fluorescent protein (GFP) specific down-regulation
      on MDA-MB231/GFP cells was comparable to that of commercially available reagents,
      without observable cytotoxicity. According to our works, S-MSN appears as an
      effective formulation for in vitro siRNA specific delivery.

PMID- 28506803
TI  - PEG coated and doxorubicin loaded multimodal Gadolinium oxide nanoparticles for
      simultaneous drug delivery and imaging applications.
AB  - We report water-in-oil microemulsion mediated synthesis of PEG1 coated Gd2O3 NPs2
      loaded with fluorescent anti-cancer drug dox3 for synchronous drug delivery,
      optical and MR4 imaging applications. These PEG covered Gd2O3 NPs loaded with dox
      (Gd-PEG-dox NPs) were found to possess spherical morphology with 13nm size as
      measured from TEM and the hydrodynamic diameter comes out to be 37nm as
      determined from DLS. Fluorescence spectra and fluorescence microscopy images
      confirmed optical activity of the NPs. The paramagnetic nature of NPs was
      affirmed by NMR line broadening effect on the spectrum of surrounding water
      protons. Therefore, these particles can be efficiently used as CA5 in MR imaging.
      In vitro analysis showed significant cellular uptake of particles by A-549 cells.
      A pH dependent drug release pattern was observed for the NPs. Cell viability
      assay performed on A-549, PANC-1 and U-87 cancerous cell lines revealed that Gd
      PEG-dox NPs are cytotoxic. On the basis of these observations, it can be
      concluded that these multi-modal paramagnetic NPs promise potential cancer
      therapy along with optical and MR imaging applications.

PMID- 28506804
TI  - Chloroquine enhances the antimycobacterial activity of isoniazid and pyrazinamide
      by reversing inflammation-induced macrophage efflux.
AB  - Mycobacterium tuberculosis (MTB) is notorious for persisting within host
      macrophages. Efflux pumps decrease intracellular drug levels, thus fostering
      persistence of MTB during therapy. Isoniazid (INH) and pyrazinamide (PZA) are
      substrates of the efflux pump breast cancer resistance protein-1 (BCRP-1), which
      is inhibited by chloroquine (CQ). In this study, BCRP-1 was found to be expressed
      on macrophages of human origin and on foamy giant cells at the site of MTB
      infection. In the current in vitro study, interferon-gamma (IFNgamma) increased
      the expression of BCRP-1 in macrophages derived from the human monocytic
      leukaemia cell line THP-1. Using a BCRP-1-specific fluorescent dye and
      radioactively labelled INH, it was demonstrated that efflux from macrophages
      increased upon activation with IFNgamma. CQ was able to inhibit active efflux and
      augmented the intracellular concentrations both of INH and the dye. In agreement,
      CQ and specific inhibition of BCRP-1 increased the antimycobacterial activity of
      INH against intracellular MTB. Although PZA behaved differently, CQ had
      comparable advantageous effects on the intracellular pharmacokinetics and
      activity of PZA. The adjunctive effects of CQ on intracellular killing of MTB
      were measurable at concentrations achievable in humans at approved therapeutic
      doses. Therefore, CQ, a widely used and worldwide available drug, may potentiate
      the efficacy of standard MTB therapy against bacteria in the intracellular
      compartment.

PMID- 28506805
TI  - HDL abnormalities in familial hypercholesterolemia: Focus on biological
      functions.
AB  - Although a selective strong elevation in the plasma level of low-density
      lipoprotein (LDL) cholesterol is the hallmark of familial hypercholesterolemia
      (FH), also other plasma lipoprotein and lipid subspecies are changed in these
      patients. Several studies in FH patients have pointed to the qualitative
      abnormalities of high-density lipoprotein (HDL) particles, including their
      triglyceride and sphingomyelin enrichment, reduced capacity to promote
      cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant
      activities, and reduced plasma levels of miRs regulating HDL-dependent
      cholesterol efflux from macrophage foam cells, typical of atherosclerotic
      lesions. Thus, accurate understanding of HDL functionality and its disturbances
      in FH may serve a better estimation of the prognosis and also provide additional
      clues when searching for novel therapeutic choices in this disease. In spite of
      such a potential promise, there has been no prior comprehensive review focusing
      on indices of HDL function in FH patients. In the present review, we aim to
      fulfill this gap by identifying measures of HDL function that are impaired in FH,
      and by providing a concise summary on the impact of different lipid-modifying
      therapies on HDL functionality in FH.

PMID- 28506806
TI  - Selective associative phonagnosia after right anterior temporal stroke.
AB  - We report the case of a 48 year old men who developed a selective impairment in
      famous voice recognition after ischemic stroke in right subcortical structures
      (lenticular nucleus and head of the caudate) and right anterior temporal lobe. He
      underwent fibrinolytic treatment. During the following days he progressively
      recovered and was discharged without neurological focal sign. Patent foramen
      ovale was found. When he got back to his house he noticed that he was unable to
      recognize the voice of his favoured singers and needed to ask who was the singer
      to his relatives. Neuropsychological examination revealed a selective impairment
      in famous voice recognition in the absence of alteration of voice perception,
      face perception and famous face recognition. All other neuropsychological domains
      were spared. In particular language, memory and executive functions were intact.
      Neuroimaging carried out by means of PET and MRI revealed two small ischemic
      lesions in the right subcortical region, involving lenticular and caudate nuclei
      and in the right temporal pole. To our knowledge, this is the first case
      described in literature of a patient showing a selective associative phonagnosia
      after right anterior temporal stroke. The present case helps to clarify the brain
      circuits underlying famous voice recognition and adds evidence in favour of a
      right hemisphere involvement in processing knowledge of familiar voices. These
      findings are discussed in relation to current models of brain organization of
      person-specific and general semantic knowledge.

PMID- 28506807
TI  - Phoneme processing skills are reflected in children's MMN responses.
AB  - Phonological awareness (PA), the core contributor in phoneme processing
      abilities, has a link to later reading skills in children. However, the
      associations between PA and neural auditory discrimination are not clear. We used
      event-related potential (ERP) methodology and neuropsychological testing to
      monitor the neurocognitive basis of phonological awareness in typically
      developing children. We measured 5-6-year-old children's (N=70) phoneme
      processing, word completion and perceptual reasoning skills and compared their
      test results to their brain responses to phonemic changes, separately for each
      test. We found that children performing better in Phoneme processing test showed
      larger mismatch negativity (MMN) responses than children scoring lower in the
      same test. In contrast, no correspondence between test scores and brain responses
      was found for Auditory closure. Thus, the results suggest that automatic auditory
      change detection is linked to phoneme awareness in preschool children.

PMID- 28506808
TI  - Should subcutaneous implantable cardioverter-defibrillators be implanted in
      patients who are candidates for continuous flow left ventricular assist device?

PMID- 28506809
TI  - Women with atrial fibrillation and type 2 diabetes have a higher incidence of
      hospitalization and undergo ablation or pacemaker implantation less frequently
      than men.
AB  - BACKGROUND: We reviewed trends from 2004 to 2013 in the incidence and outcomes
      for atrial fibrillation (AF) in Spanish patients with type 2 diabetes mellitus
      (T2DM) comparing women and men. METHODS: We used national hospital discharge data
      including all T2DM patients discharged from the hospital after AF. Patients with
      AF in the primary diagnosis field were selected. Discharges were grouped by sex.
      Incidence was calculated overall and stratified by sex. We analyzed diagnostic
      and therapeutic procedures, patient comorbidities, CHA2DS2-VASc score, length of
      hospital stay, readmission rates and in-hospital mortality (IHM). RESULTS: We
      identified a total of 214,457 admissions for AF. Patients with T2DM accounted for
      21.1% (19,505 men and 25,954 women). Women with T2DM had a significantly higher
      incidence of AF compared to men over the study period (IRR 1.33;95%CI 1.31-1.35).
      Women were significantly older (77.24+/-8.69years) than men (72.62+/-10.28years),
      had higher prevalences of obesity and hypertension, and higher CHA2DS2-VASc
      score. Women less frequently underwent ablation (3.21% vs. 1.54%; p<0.001) and
      received an implanted pacemaker (14.3% vs. 8.16%; p<0.001) than men. Crude IHM
      was 2.81% for women and 2.48% for men (p=0.030). Sex was not associated with a
      higher IHM after multivariable adjustment. CONCLUSIONS: Our study demonstrates an
      increase in hospitalization for AF in diabetic women. Women were older, had a
      higher comorbidity index and had CHAD2DS2-VASc score than men. Women with AF and
      T2DM undergo ablation or pacemaker implantation less frequently than their male
      counterparts. After multivariable adjustment sex did not predict mortality during
      admissions for AF.

PMID- 28506810
TI  - A man with dyspnea, chest pain and leukocytosis.

PMID- 28506811
TI  - A young woman with fever and low visual acuity.

PMID- 28506812
TI  - A 33year-old woman with calciphylaxis, diabetic kidney disease and abdominal
      pain.

PMID- 28506813
TI  - The Effects of Natural Clinoptilolite and Nano-Sized Clinoptilolite
      Supplementation on Glucose Levels and Oxidative Stress in Rats With Type 1
      Diabetes.
AB  - OBJECTIVE: Oxidative stress has a major role in development of diabetic
      complications. In this study we investigated whether clinoptilolite and nano
      sized clinoptilolite could reduce hyperglycemia and oxidative stress in
      streptozotocin-induced diabetic rats and attempted to determine which
      intervention was more effective. METHODS: Thirty-six rats were randomly allocated
      to 2 groups; 1 group was randomly chosen as a diabetic group and injected with
      streptozotocin (60 mg/kg body weight in 0.1 mol/L sodium citrate buffer, pH 4.5)
      to induce diabetes. Three days after diabetes induction, each group (diabetic
      group and nondiabetic group) was randomly divided into 3 subgroups of 6 animals
      each ([1] control, [2] 1% clinoptilolite/food, [3] 1% nano-sized
      clinoptilolite/food). Supplementation was continued for 28 days. Blood glucose
      was measured 3 times, at the beginning of the study and on the 14th and 28th
      days. Activity of antioxidant enzymes, including glutathione peroxidase and
      superoxide dismutase, and levels of total antioxidant capacity, as well as
      malondialdehyde, were evaluated. RESULTS: Blood glucose and malondialdehyde were
      significantly elevated, but there were no statistically significant changes in
      superoxide dismutase, glutathione peroxidase or total antioxidant capacity in
      diabetic rats. In diabetic rats treated with nano-sized clinoptilolite, blood
      glucose decreased to near normal levels (12.4 vs. 27.5 mmol/L). No significant
      changes were found in the other groups. None of the oxidative stress indices
      showed significant changes in either the treated or untreated rats. CONCLUSION:
      Nano-sized clinoptilolite exerted a hypoglycemic effect in streptozotocin-induced
      diabetic rats but had no significant influence on oxidative stress markers.

PMID- 28506815
TI  - Postpartum Diabetes Testing Rates after Gestational Diabetes Mellitus in Canadian
      Women: A Population-Based Study.
AB  - OBJECTIVES: We assessed the rate and type of postpartum glycemic testing in women
      with impaired glucose tolerance of pregnancy (IGTp) and gestational diabetes
      mellitus (GDM). We examined whether the likelihood of testing was modulated by
      patients' characteristics and pregnancy outcomes. METHODS: Our population-level
      cohort study included data from 132,905 pregnancies between October 1, 2008, and
      December 31, 2011, in Alberta, Canada. Laboratory data within 270 days before and
      1 year after delivery were used to identify pregnancies involving IGTp/GDM and
      postpartum glycemic testing, respectively. Logistic regression was used to
      identify maternal and pregnancy factors associated with postpartum testing.
      RESULTS: A total of 8,703 pregnancies were affected by IGTp (n=3669) or GDM
      (n=5034) as defined by the prevailing Canadian Diabetes Association 2008 Clinical
      Practice Guidelines for the Prevention and Management of Diabetes in Canada. By 1
      year postpartum, 55.1% had undergone glycemic assessments. Of those, 59.7% had
      had 75 g oral glucose tolerance tests, 17.4% had had glycated hemoglobin tests
      without oral glucose tolerance tests and 22.9% had had only fasting or random
      glucose tests. Women with IGTp or GDM, respectively, who were younger, smokers
      and residing in rural areas and whose labours were not induced were less likely
      to be tested postpartum. Having large for gestational age infants was also
      associated with a lower likelihood of postpartum testing in women with GDM.
      CONCLUSIONS: Despite a universal health-care system in Canada, many women with
      IGTp or GDM do not undergo postpartum glucose testing. Maternal and pregnancy
      characteristics influence postpartum testing and provide valuable information for
      creating targeted strategies to improve postpartum testing in this group of high
      risk women.

PMID- 28506814
TI  - The Relation of Type 2 Diabetes and Breast Cancer Incidence in Asian, Hispanic
      and African American Populations-A Review.
AB  - In addition to rising type 2 diabetes and breast cancer incidence rates
      worldwide, diabetes may also increase breast cancer risk, and the association may
      vary by ethnicity. This review summarizes published data evaluating the
      association between diabetes and breast cancer in women of Asian, Hispanic and
      African American ancestry while considering a measure of obesity, body mass index
      (BMI). Published reports were identified through a search of PubMed and previous
      publications. Of 15 age-adjusted studies, 11 reported on Asian women from various
      countries, 3 on Hispanics and 1 on African Americans. The studies of Asian women
      described significant associations in 8 reports, with risk estimates of 1.5 to
      8.4, but 3 were case-control studies and 6 did not adjust for BMI. The 3 case
      control studies of Hispanic people included BMI, but only 1 detected a weak
      association between diabetes and breast cancer risk and was limited to
      postmenopausal women. The only study of African American women was a prospective
      cohort, and it showed no significant association between diabetes and breast
      cancer. In contrast to a 10% to 20% higher risk for breast cancer associated with
      diabetes reported for Caucasian women, there is little evidence for an
      association in Hispanics and African Americans. Although several studies of Asian
      women included in our review reported a higher risk for breast cancer with
      diabetes, methodologic shortcomings, such as lack of adjustment for obesity, use
      of a general population as controls, case-control design and small sample sizes,
      raise questions about the validity of the findings.

PMID- 28506817
TI  - In vitro CYP-mediated drug metabolism in the zebrafish (embryo) using human
      reference compounds.
AB  - The increasing use of zebrafish embryos as an alternative model for toxicological
      and pharmacological studies necessitates a better understanding of xenobiotic
      biotransformation in this species. As cytochrome P450 enzymes (CYPs) play an
      essential role in this process, in vitro drug metabolism of four human CYP
      specific substrates, i.e. dextromethorphan (DXM), diclofenac (DIC), testosterone
      (TST) and midazolam (MDZ) was investigated in adult male and female zebrafish,
      and in zebrafish embryos and larvae up to 120hours post-fertilization. Substrate
      depletion and production of their respective metabolites were measured using
      tandem quadrupole UPLC-MS/MS. Human liver microsomes were used as positive
      control. Adult zebrafish produced the two major human metabolites of DIC and DXM.
      For DIC the metabolite ratio was similar to that in man, whereas it was different
      for DXM. For TST, the major human metabolite could not be detected and MDZ was
      not metabolized. No sex-related differences were detected, except for the higher
      TST depletion rate in adult females. Zebrafish embryos and larvae showed no or
      only low biotransformation capacity. In conclusion, in vitro CYP-mediated drug
      metabolism in adult zebrafish shows differences compared to man and appears to be
      lacking in the early zebrafish life stages. As CYP-mediated drug metabolism in
      zebrafish may not be predictive for the one in man, we recommend including the
      zebrafish in metabolic stability testing of new compounds when considering non
      clinical species for human risk assessment.

PMID- 28506818
TI  - Measuring inhibition of monoamine reuptake transporters by new psychoactive
      substances (NPS) in real-time using a high-throughput, fluorescence-based assay.
AB  - The prevalence and use of new psychoactive substances (NPS) is increasing and
      currently over 600 NPS exist. Many illicit drugs and NPS increase brain monoamine
      levels by inhibition and/or reversal of monoamine reuptake transporters (DAT, NET
      and SERT). This is often investigated using labor-intensive, radiometric endpoint
      measurements. We investigated the applicability of a novel and innovative assay
      that is based on a fluorescent monoamine mimicking substrate. DAT, NET or SERT
      expressing human embryonic kidney (HEK293) cells were exposed to common drugs
      (cocaine, dl-amphetamine or MDMA), NPS (4-fluoroamphetamine, PMMA, alpha-PVP, 5
      APB, 2C-B, 25B-NBOMe, 25I-NBOMe or methoxetamine) or the antidepressant
      fluoxetine. We demonstrate that this fluorescent microplate reader-based assay
      detects inhibition of different transporters by various drugs and discriminates
      between drugs. Most IC50 values were in line with previous results from
      radiometric assays and within estimated human brain concentrations. However,
      phenethylamines showed higher IC50 values on hSERT, possibly due to experimental
      differences. Compared to radiometric assays, this high-throughput fluorescent
      assay is uncomplicated, can measure at physiological conditions, requires no
      specific facilities and allows for kinetic measurements, enabling detection of
      transient effects. This assay is therefore a good alternative for radiometric
      assays to investigate effects of illicit drugs and NPS on monoamine reuptake
      transporters.

PMID- 28506816
TI  - Ghrelin suppresses cholecystokinin (CCK), peptide YY (PYY) and glucagon-like
      peptide-1 (GLP-1) in the intestine, and attenuates the anorectic effects of CCK,
      PYY and GLP-1 in goldfish (Carassius auratus).
AB  - Ghrelin is an important gut-derived hormone with an appetite stimulatory role,
      while most of the intestinal hormones, including cholecystokinin (CCK), peptide
      YY (PYY) and glucagon-like peptide-1 (GLP-1), are appetite-inhibitors. Whether
      these important peptides with opposing roles on food intake interact to regulate
      energy balance in fish is currently unknown. The aim of this study was to
      characterize the putative crosstalk between ghrelin and CCK, PYY and GLP-1 in
      goldfish (Carassius auratus). We first determined the localization of CCK, PYY
      and GLP-1 in relation to ghrelin and its main receptor GHS-R1a (growth hormone
      secretagogue 1a) in the goldfish intestine by immunohistochemistry.
      Colocalization of ghrelin/GHS-R1a and CCK/PYY/GLP-1 was found primarily in the
      luminal border of the intestinal mucosa. In an intestinal explant culture, a
      significant decrease in prepro-cck, prepro-pyy and proglucagon transcript levels
      was observed after 60min of incubation with ghrelin, which was abolished by
      preincubation with the GHS-R1a ghrelin receptor antagonist [D-Lys3]-GHRP-6
      (except for proglucagon). The protein expression of PYY and GLP-1 was also
      downregulated by ghrelin. Finally, intraperitoneal co-administration of CCK, PYY
      or GLP-1 with ghrelin results in no modification of food intake in goldfish.
      Overall, results of the present study show for the first time in fish that
      ghrelin exerts repressive effects on enteric anorexigens. It is likely that these
      interactions mediate the stimulatory effects of ghrelin on feeding and metabolism
      in fish.

PMID- 28506819
TI  - Prediction of delivery of organic aerosols onto air-liquid interface cells in
      vitro using an electrostatic precipitator.
AB  - To better characterize biological responses to atmospheric organic aerosols, the
      efficient delivery of aerosol to in vitro lung cells is necessary. In this study,
      chamber generated secondary organic aerosol (SOA) entered the commercialized
      exposure chamber (CULTEX(r) Radial Flow System Compact) where it interfaced with
      an electrostatic precipitator (ESP) (CULTEX(r) Electrical Deposition Device) and
      then deposited on a particle collection plate. This plate contained human lung
      cells (BEAS-2B) that were cultured on a membrane insert to produce an air-liquid
      interface (ALI). To augment in vitro assessment using the ESP exposure device,
      the particle dose was predicted for various sampling parameters such as particle
      size, ESP deposition voltage, and sampling flowrate. The dose model was evaluated
      against the experimental measured mass of collected airborne particles. The high
      flowrate used in this study increased aerosol dose but failed to achieve cell
      stability. For example, RNA in the ALI BEAS-2B cells in vitro was stable at
      0.15L/minute but decayed at high flowrates. The ESP device and the resulting
      model were applied to in vitro studies (i.e., viability and IL-8 expression) of
      toluene SOA using ALI BEAS-2B cells with a flowrate of 0.15L/minute, and no
      cellular RNA decay occurred.

PMID- 28506820
TI  - Seasonal variation of hospital violence, seclusion and restraint in a forensic
      psychiatric hospital.
AB  - Several epidemiological studies have reported seasonal patterns in both violent
      and self-destructive behaviour. However, a few studies on hospital violence have
      found contradictory results. The aim of this study was to investigate whether
      there was any seasonal variation of violence in a forensic psychiatric hospital
      providing care for persons suffering from psychotic disorders and violent or self
      destructive behaviour. Seasonal variation of the prevalence of seclusion and
      restraint was also investigated. Reports of violent incidents and seclusion and
      restraint statistics from between 2007 and 2012 were examined with Poisson
      regression analysis. There was significant variation in the prevalence of
      seclusion and restraint between months (p<0.001), and between seasons (p<0.001).
      Monthly prevalence of seclusion and restraint was the lowest in January compared
      to other months. In comparison, the prevalence of seclusion and restraint was
      lower in winter than in other seasons. In a hospital with persons suffering from
      psychotic disorders, no significant variation of violence or self-destructive
      behaviour was found, similarly as in the society. By contrast, the prevalence of
      seclusion and restraint showed marked seasonality. Variation in the prevalence of
      seclusion and restraint was not consistent with the variance in violence, which
      implies that the use of coercive measures is related to seasonal variation among
      staff.

PMID- 28506821
TI  - Development of a bioassay as a measure of drozitumab-mediated apoptosis induced
      by soluble Fc gamma receptors.
AB  - Drozitumab is an agonistic therapeutic monoclonal antibody (mAb) against the pro
      apoptotic death receptor 5 (DR5). In vitro cell killing assays using drozitumab
      have traditionally required cross-linking with anti-Fc antibody to amplify the
      pro-apoptotic signal, although drozitumab shows activity in in vivo tumor models
      without artificial cross-linking. Recently it has been shown that FcgammaR
      expressing cells play an important role in the activity of drozitumab by
      mediating cross-linking in vivo (Wilson et al., 2011). To provide a more
      biologically relevant alternative to cross-linking with anti-Fc antibody in in
      vitro bioassays, methods for cross-linking with soluble FcgammaR extracellular
      domain (ECD) were developed in this work. FcgammaR cross-linking methods
      developed in this work were assessed in solution, bead-bound, and plate-bound
      assay formats, as well as a cell-based assay format. The assays showed
      reproducible drozitumab dose-response curves in the concentration range of 5
      20,000ng/mL and had acceptable precision and accuracy. The assays are also able
      to detect degradative changes in drozitumab samples subjected to thermal stress.
      The data suggest that FcgammaR cross-linking of drozitumab is a viable
      alternative to anti-Fc cross-linking of drozitumab to measure effector mediated
      apoptosis of drozitumab in vitro.

PMID- 28506822
TI  - The effect of prophylactic vertebroplasty on the incidence of proximal junctional
      kyphosis and proximal junctional failure following posterior spinal fusion in
      adult spinal deformity: a 5-year follow-up study.
AB  - BACKGROUND CONTEXT: The incidence of proximal junctional kyphosis (PJK) ranges
      from 5% to 46% following adult spinal deformity surgery. Approximately 66% to 76%
      of PJK occurs within 3 months of surgery. A subset of these patients, reportedly
      26% to 47%, develop proximal junctional failure (PJF) within 6 months
      postoperatively. To date, there are no studies evaluating the impact of
      prophylactic vertebroplasty on PJK and PJF incidence at long-term follow-up.
      PURPOSE: The purpose of this study is to evaluate the long-term radiographic and
      clinical outcomes, and incidence of PJK and PJF, after prophylactic
      vertebroplasty for long-segment thoracolumbar posterior spinal fusion (PSF).
      STUDY DESIGN: This is a prospective cohort study. PATIENT SAMPLE: Thirty-nine
      patients, of whom 87% were female, who underwent two-level prophylactic
      vertebroplasty at the upper instrumented and supra-adjacent vertebrae at the time
      of index PSF were included in this study. OUTCOME MEASURES: Clinical outcomes
      were assessed using the Scoliosis Research Society-22 (SRS-22), and Short-Form
      (SF) 36 questionnaires, and the Oswestry Disability Index (ODI). Radiographic
      parameters including PJK angle, and coronal and sagittal alignment, were
      calculated, along with relevant perioperative complications and revision rates.
      METHODS: Of the 41 patients who received two-level prophylactic vertebroplasty at
      the upper instrumented and supra-adjacent vertebrae at the time of index PSF, and
      comprised a cohort with previously published 2-year follow-up data, 39 (95%)
      completed 5-year follow-up (average: 67.6 months). Proximal junctional kyphosis
      was defined as a change in the PJK angle >=10 degrees  between the immediate
      postoperative and final follow-up radiograph. Proximal junctional failure was
      defined as acute proximal junctional fracture, fixation failure, or kyphosis
      requiring extension of fusion within the first 6 months postoperatively. RESULTS:
      Thirty-nine patients with a mean age of 65.6 (41-87) years were included in this
      study. Of the 39 patients, 28.2% developed PJK (11: 7.7% at 2 years, 20.5%
      between 2 and 5 years), and 5.1% developed acute PJF. Two of the 11 PJK patients
      required revision for progressive worsening of the PJK. There were no proximal
      junctional fractures. There was no significant difference in preoperative,
      immediate postoperative, and final follow-up measurements of thoracic kyphosis,
      lumbar lordosis, and coronal or sagittal alignment between patients who developed
      PJK, PJF, or neither (p>.05). There was no significant difference in ODI, SRS-22,
      or SF-36 scores between those with and without PJK or PJF (p>.05). CONCLUSIONS:
      This long-term follow-up demonstrates that prophylactic vertebroplasty may
      minimize the risk for junctional failure in the early postoperative period.
      However, it does not appear to decrease the incidence of PJK at 5 years.

PMID- 28506823
TI  - Hyperammonemia compromises glutamate metabolism and reduces BDNF in the rat
      hippocampus.
AB  - Ammonia is putatively the major toxin associated with hepatic encephalopathy
      (HE), a neuropsychiatric manifestation that results in cognitive impairment, poor
      concentration and psychomotor alterations. The hippocampus, a brain region
      involved in cognitive impairment and depressive behavior, has been studied less
      than neocortical regions. Herein, we investigated hippocampal astrocyte
      parameters in a hyperammonemic model without hepatic lesion and in acute
      hippocampal slices exposed to ammonia. We also measured hippocampal BDNF, a
      neurotrophin commonly related to synaptic plasticity and cognitive deficit, and
      peripheral S100B protein, used as a marker for brain damage. Hyperammonemia
      directly impaired astrocyte function, inducing a decrease in glutamate uptake and
      in the activity of glutamine synthetase, in turn altering the glutamine-glutamate
      cycle, glutamatergic neurotransmission and ammonia detoxification itself.
      Hippocampal BDNF was reduced in hyperammonemic rats via a mechanism that may
      involve astrocyte production, since the same effect was observed in astrocyte
      cultures exposed to ammonia. Ammonia induced a significant increase in S100B
      secretion in cultured astrocytes; however, no significant changes were observed
      in the serum or in cerebrospinal fluid. Data demonstrating hippocampal
      vulnerability to ammonia toxicity, particularly due to reduced glutamate uptake
      activity and BDNF content, contribute to our understanding of the
      neuropsychiatric alterations in HE.

PMID- 28506824
TI  - Hypoxia and nicotine effects on Pituitary adenylate cyclase activating
      polypeptide (PACAP) and its receptor 1 (PAC1) in the developing piglet brainstem.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate
      receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden
      Infant Death Syndrome (SIDS). Two main risk factors for SIDS are prone sleeping
      and cigarette smoke exposure. Using piglet models of these risk factors,
      intermittent hypercapnic hypoxia (IHH-mimicking rebreathing in prone position)
      and nicotine (main reinforcing element of cigarettes), this study aimed to
      determine their effects on PACAP and PAC1 protein expression in the medulla. IHH
      was delivered for 1 (n=7), 2 (n=6), 3 (n=6) and 4 (n=7) days prior to euthanasia
      at 13-14days of age, while nicotine (n=7) was continuous for the first 14days of
      life. An additional group of combined nicotine and 1day IHH (1DIHH) was studied
      to determine the combined effects of the risk factors. Changes in expression were
      seen after the acute 1DIHH exposure (none after repeated daily exposures) and
      included a decrease in PACAP in the dorsal motor nucleus of vagus (DMNV;
      p=0.024), nucleus of the solitary tract (NTS; p=0.024) and the gracile nucleus
      (GRAC; p=0.001), and a decrease in PAC1 in the NTS (p=0.01). No PACAP change was
      noted in the nicotine-exposed piglets, however, a decrease in PAC1 was found in
      the DMNV (p=0.02). IHH exposure in piglets with pre-exposure to nicotine led to a
      significant decrease in PACAP in the Grac (p=0.04) but had no effect on PAC1.
      These findings show for the first time, the vulnerability of PACAP in the
      brainstem during early development to an acute hypercapnic hypoxic exposure and
      that those effects are greater than from nicotine exposure.

PMID- 28506825
TI  - Multiple drug resistance in Haemophilus influenzae isolated from patients in
      Bangkok, Thailand.

PMID- 28506826
TI  - An X-chromosome linked mouse model (Ndufa1S55A) for systemic partial Complex I
      deficiency for studying predisposition to neurodegeneration and other diseases.
AB  - The respiratory chain Complex I deficiencies are the most common cause of
      mitochondrial diseases. Complex I biogenesis is controlled by 58 genes and at
      least 47 of these cause mitochondrial disease in humans. Two of these are X
      chromosome linked nuclear (nDNA) genes (NDUFA1 and NDUFB11), and 7 are
      mitochondrial (mtDNA, MT-ND1-6, -4L) genes, which may be responsible for sex
      dependent variation in the presentation of mitochondrial diseases. In this study,
      we describe an X-chromosome linked mouse model (Ndufa1S55A) for systemic partial
      Complex I deficiency. By homologous recombination, a point mutation T > G within
      55th codon of the Ndufa1 gene was introduced. The resulting allele Ndufa1S55A
      introduced systemic serine-55-alanine (S55A) mutation within the MWFE protein,
      which is essential for Complex I assembly and stability. The S55A mutation caused
      systemic partial Complex I deficiency of ~50% in both sexes. The mutant males
      (Ndufa1S55A/Y) displayed reduced respiratory exchange ratio (RER) and produced
      less body heat. They were also hypoactive and ate less. They showed age-dependent
      Purkinje neurons degeneration. Metabolic profiling of brain, liver and serum from
      males showed reduced heme levels in mutants, which correlated with altered
      expressions of Fech and Hmox1 mRNAs in tissues. This is the first genuine X
      chromosome linked mouse model for systemic partial Complex I deficiency, which
      shows age-dependent neurodegeneration. The effect of Complex I deficiency on
      survival patterns of males vs. females was different. We believe this model will
      be very useful for studying sex-dependent predisposition to both spontaneous and
      stress-induced neurodegeneration, cancer, diabetes and other diseases.

PMID- 28506827
TI  - How tumor growth can be influenced by delayed interactions between cancer cells
      and the microenvironment?
AB  - Although recent advances in oncology emphasized the role of microenvironment in
      tumor growth, the role of delays for modeling tumor growth is still uncertain. In
      this paper, we considered a model, describing the interactions of tumor cells
      with their microenvironment made of immune cells and host cells, in which we
      inserted, as suggested by the clinicians, two time delays, one in the
      interactions between tumor cells and immune cells and, one in the action of
      immune cells on tumor cells. We showed analytically that the singular point
      associated with the co-existence of the three cell populations loses its
      stability via a Hopf bifurcation. We analytically calculated a range of the
      delays over which tumor cells are inhibited by immune cells and over which a
      period-1 limit cycle induced by this Hopf bifurcation is observed. By using a
      global modeling technique, we investigated how the dynamics observed with two
      delays can be reproduced by a similar model without delays. The effects of these
      two delays were thus interpreted in terms of interactions between the cell
      populations.

PMID- 28506828
TI  - Stringency of bacterial prolipoprotein signal peptidase (LspA) in recognition of
      signal peptides - Structure-function correlation.
AB  - Bacterial lipid modification of proteins is an essential post-translational event
      committed by Phosphatidylglycerol: prolipoprotein diacylglyceryl transferase
      (Lgt) by catalysing diacyglyceryl transfer from Phosphatidylglycerol to cysteine
      present in the characteristic 'lipobox' ([LVI] (-3) [ASTVI] (-2) [GAS] (-1) C
      (+1)) of prolipoprotein signal peptides. This is then followed by the cleavage of
      the signal peptide by lipoprotein-specific signal peptidase (LspA). It had been
      known for long that threonine at the -1 position allows diacylglyceryl
      modification by Lgt, but not signal peptide cleavage by LspA. We have addressed
      this unexplained stringency by computational analysis of the recently published
      3D structure of LspA with its competitive inhibitor as well as transition state
      analogue, globomycin using PyMoL viewing tool and VADAR (Volume, Area, Dihedral
      Angle Reporter) web server. The propensity to form hydrogen bond (2.9a) between
      the hydroxyl group of threonine (not possible with serine) and the NH of the
      lipid-modified cysteine, possible only in the transition state, will prevent the
      protonation of NH of the leaving peptide and therefore its cleavage. This
      knowledge could be useful for designing inhibitors of this essential pathway in
      bacteria or for engineering LspA.

PMID- 28506829
TI  - An asymmetric dimeric structure of TrmJ tRNA methyltransferase from Zymomonas
      mobilis with a flexible C-terminal dimer.
AB  - The tRNA methyltransferase J (TrmJ) and D (TrmD) catalyze the transferring
      reaction of a methyl group to the tRNA anticodon loop. They commonly have the N
      terminal domain (NTD) and the C-terminal domain (CTD). Whereas two monomeric CTDs
      symmetrically interact with a dimeric NTD in TrmD, a CTD dimer has exhibited an
      asymmetric interaction with the NTD dimer in the presence of a product. The
      elucidated apo-structure of the full-length TrmJ from Zymomonas mobilis ZM4 shows
      a dimeric CTD that asymmetrically interacts with the NTD dimer, thereby
      distributing non-symmetrical potential charge on the both side of the protein
      surface. Comparison with the product-bound structures reveals a local re
      orientation of the two arginine-containing loop at the active site, which
      interacts with the product. Further, the CTD dimers have diverse orientations
      compared to the NTD dimers, suggesting their flexibility. These data indicate
      that an asymmetric interaction between the NTD dimer and the CTD dimer is a
      common structural feature among TrmJ proteins, regardless of the presence of a
      substrate or a product.

PMID- 28506830
TI  - Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via
      affecting APC-Th1 development in mice.
AB  - Gut microbiota is critical for maintaining body immune homeostasis and thus
      affects tumor growth and therapeutic efficiency. Here, we investigated the link
      between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell
      transplantation, and explored the underlying mechanism. We found disruption of
      gut microbiota by pretreating mice with antibiotics promote tumor growth and
      remodeling the immune compartment within the primary tumor. Indeed, gut microbial
      dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor,
      together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as
      well as defective Th1 cytokines, including IFNgamma, TNFalpha, IL12p40, and
      IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell
      proliferation and IFNgamma secretion. However, oral administration of LPS
      restored the immune surveillance effects and thus inhibited tumor growth in the
      antibiotics induced gut microbiota dysbiosis group. Taken together, these data
      highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor
      initiation, while LPS supplementation would restore the effective immune
      surveillance and repress tumor initiation.

PMID- 28506831
TI  - Alpha B-crystallin promotes the invasion and metastasis of colorectal cancer via
      epithelial-mesenchymal transition.
AB  - Alpha B-crystallin (CRYAB, HSPB5) is a protein that was first discovered in the
      lens of the eye. It is a member of the small heat-shock protein family (sHsps).
      CRYAB functions primarily as a molecular chaperone to prevent the aggregation and
      degradation of damaged unfolded proteins due to cellular damage resulting from
      heat shock, radiation, oxidative stress, and other insults, thereby promoting
      cell survival and preventing apoptosis. In recent years, the role of CRYAB in
      tumorigenesis, tumor invasion, and metastasis has received increasing attention.
      CRYAB is highly expressed in a variety of cancers, including breast cancer, head
      and neck cancer, and kidney cancer, and is likely associated with the prognosis
      of cancer. However, few studies have examined CRYAB in colorectal cancer (CRC).
      To study the effect of CRYAB on CRC, we transfected the CRC cell line SW480,
      which expresses high levels of CRYAB, with a lentiviral vector that inhibits
      CRYAB expression. The messenger RNA (mRNA) and protein expression of CRYAB was
      examined in the transfected SW480 cells (Si-CRYAB) using quantitative real-time
      polymerase chain reaction (qPCR) and Western blotting (WB) assays. Moreover, a
      growth curve was plotted to examine the proliferation of Si-CRYAB cells, and
      transwell assays were used to examine the migration of Si-CRYAB cells. Apoptosis
      and the cell cycle were examined in Si-CRYAB cells using flow cytometry (FCM),
      and the tumorigenic capability of Si-CRYAB cells was assessed in a nude mouse
      tumor model. Immunohistochemistry (IHC) was employed to examine CRYAB protein
      expression and the markers of epithelial-mesenchymal transition (EMT), such as E
      cadherin, fibronectin, vimentin, and slug, in tumor tissues from nude mice and
      clinical invasive CRC and hepatic metastasis specimens. The qPCR and WB results
      showed that CRYAB was downregulated at the protein and mRNA level in Si-CRYAB
      cells, and the growth curve indicated that the proliferation of Si-CRYAB cells
      was reduced. Moreover, Si-CRYAB cells exhibited reduced migration capability in
      the transwell assay as well as increased apoptosis and G1 arrest in the FCM
      assay. The tumorigenesis study in nude mice showed that Si-CRYAB cells formed
      smaller tumors, indicating decreased tumorigenic capability. IHC results showed
      reduced CRYAB expression and lower levels of EMT in Si-CRYAB cells, whereas
      clinical specimens of invasive CRC and hepatic metastases exhibited elevated
      CRYAB expression and enhanced levels of EMT. These results demonstrated that
      CRYAB promoted the invasion and metastasis of CRC tumor cells via EMT.

PMID- 28506832
TI  - Regarding "Proximal Tubal Patency Demonstrated Through Air Infusion During
      Flexible Office Hysteroscopy Is Predictive of Whole Tubal Patency".

PMID- 28506833
TI  - Response to Letter to the Editor: Author's Reply.

PMID- 28506834
TI  - Safety evaluation of dermal exposure to phthalates: Metabolism-dependent
      percutaneous absorption.
AB  - Phthalates, known as reproductive toxicants and endocrine disruptors, are widely
      used as plasticizers in polyvinyl chloride products. The present study was
      conducted for risk identification of dermal exposure to phthalates. When dibutyl
      phthalate was applied to the skin of hairless rats and humans, only monobutyl
      phthalate appeared through the skin, and the permeability of the skin was higher
      than that after the application of the monoester directly. The inhibition of skin
      esterases made the skin impermeable to the metabolite following dermal exposure
      to dibutyl ester, whereas removal of the stratum corneum from the skin did not
      change the skin permeation behavior. Similar phenomena were observed for benzyl
      butyl phthalate. The skin permeability of monobenzyl phthalate was higher than
      that of monobutyl phthalate in humans, although the reverse was observed in rats.
      Species difference in skin permeation profile corresponded to the esterase
      activity of the skin homogenate. Di(2-ethylhexyl) phthalate, which was not
      metabolized by esterases in the skin, was not transported across the skin. These
      results suggest that highly lipophilic phthalates may be transported easily
      across the stratum corneum lipids. The water-rich viable layer may become
      permeable to these phthalates by their metabolism into monoesters, which are
      relatively hydrophilic. Skin metabolism is essential to the percutaneous
      absorption of phthalates. Because esterase activity has large inter-individual
      differences, further study will be needed for individual risk identification of
      dermal exposure to phthalates.

PMID- 28506835
TI  - Impact of common clandestine structural modifications on synthetic cathinone
      "bath salt" pharmacokinetics.
AB  - Since 2009, the synthetic cathinones ("bath salts") have risen in popularity as
      drugs of abuse. However, there are a paucity of studies that have determined the
      impact of functional group modifications in the synthetic cathinone chemical
      structures on plasma and central nervous system (CNS) pharmacokinetics. In the
      present study, we investigated the in vivo plasma and CNS pharmacokinetics of
      three synthetic cathinones whose structures differ by lengthening of the alpha
      alkyl chain: methylone (-CH3), butylone (-CH2CH3), and pentylone (-CH2CH2CH3).
      Male Sprague-Dawley rats were treated with a 20mg/kg subcutaneous dose of the
      individual synthetic cathinone. Blood samples were obtained at specific times
      from a jugular vein cannula over an 8hour period. Over a separate three-hour
      period, CNS samples were obtained using a microdialysis cannula surgically
      implanted into the lateral ventricle. In the plasma, pentylone, with the longest
      alpha-alkyl chain, displayed the highest Cmax and AUC0-infinity, and the longest
      t1/2. Decreasing the alpha-alkyl chain length as in butylone and methylone
      significantly decreased the Cmax, AUC0-infinity, and t1/2. The plasma
      pharmacokinetic values are consistent with the greater lipophilicity associated
      with alpha-alkyl side chain lengthening. Conversely, in the CNS, methylone and
      butylone displayed higher Cmax and AUC0-infinity values than pentylone. These
      contrary findings in the CNS and plasma demonstrate that lengthening of the alpha
      alkyl chain of methylone, butylone, and pentylone yields differential
      pharmacokinetic properties in the CNS as compared to the plasma.

PMID- 28506836
TI  - A comprehensive review of metal-induced cellular transformation studies.
AB  - In vitro transformation assays not only serve practical purposes in screening for
      potential carcinogenic substances in food, drug, and cosmetic industries, but
      more importantly, they provide a means of understanding the critical biological
      processes behind in vivo cancer development. In resemblance to cancer cells in
      vivo, successfully transformed cells display loss of contact inhibition, gain of
      anchorage independent growth, resistant to proper cell cycle regulation such as
      apoptosis, faster proliferation rate, potential for cellular invasion, and
      ability to form tumors in experimental animals. Cells purposely transformed using
      metal exposures enable researchers to examine molecular changes, dissect various
      stages of tumor formation, and ultimately elucidate metal induced cancer mode of
      action. For practical purposes, this review specifically focuses on studies
      incorporating As-, Cd-, Cr-, and Ni-induced cell transformation. Through
      investigating and comparing an extensive list of studies using various methods of
      metal-induced transformation, this review serves to bridge an information gap and
      provide a guide for avoiding procedural discrepancies as well as maximizing
      experimental efficiency.

PMID- 28506837
TI  - The roles of actin cytoskeleton and actin-associated protein Crn1p in trap
      formation of Arthrobotrys oligospora.
AB  - Nematode-trapping fungi include a variety of species capable of generating
      specific trapping devices to capture nematodes and the production of devices is
      also an indicator of a switch from saprophytic to predacious lifestyles. Traps
      are developed from vegetative mycelia, but they are quite different from hyphae
      in both morphological and physiological characteristics. Therefore, the molecular
      mechanisms underlying their formation have attracted much attention. In this
      investigation, Arthrobotrys oligospora, a nematode-trapping fungus, has three
      dimensional networks and genomics and proteomics were recently performed, so as
      to reveal the relationship between actin cytoskeleton and trap formation. Both
      actin staining via FITC-phalloidin and treatment of actin polymerization
      inhibitor Lat-B illustrated that the actin cytoskeleton played an important role
      in trap development. Furthermore, absence of the conserved actin-associated
      protein Crn1p caused a structural defect of traps and failure to infect
      nematodes. It was observed that mutant Deltacrn1 represented a reduced number of
      rings and a lower complexity of three-dimensional networks, likely due to the
      disturbance of actin branching. Collectively, our study confirmed the involvement
      of the actin cytoskeleton as well as the conserved actin-associated protein Crn1p
      in trap formation. It further suggested the manners in which Crn1p influences the
      development of three-dimensional networks in A. oligospora.

PMID- 28506838
TI  - Phylogenomic analysis of the complete sequence of a gastroenteritis-associated
      cetacean adenovirus (bottlenose dolphin adenovirus 1) reveals a high degree of
      genetic divergence.
AB  - Adenoviruses are common pathogens in vertebrates, infecting a wide range of
      hosts, but only having rarely been detected and correlated with disease in
      cetaceans. This article describes the first complete genomic sequence of a
      cetacean adenovirus, bottlenose dolphin adenovirus 1 (BdAdV-1), detected in
      captive bottlenose dolphin population (Tursiops truncatus) suffering from self
      limiting gastroenteritis. The complete genome sequence of BdAdV-1 was recovered
      from data generated by high-throughput sequencing and validated by Sanger
      sequencing. The genome is 34,080bp long and has 220 nucleotides long inverted
      terminal repeats. A total of 29 coding sequences were identified, 26 of which
      were functionally annotated. Among the unusual features of this genome is a
      remarkably long 4380bp E3 ORF1, that displays no sequence homology with the
      corresponding E3 regions of other adenoviruses. In addition, the fiber protein
      only has 26% identity with fiber proteins described in other adenoviruses. Three
      hypothetical proteins were predicted. The phylogenetic analysis indicates that
      the closest known relative to BdAdV-1 is an adenovirus detected in bottlenose
      dolphin (KR024710), with an amino acid sequence identity between 36 and 79%
      depending on the protein. Based on the phylogenic analysis, the BdAdV-1 appears
      to have co-evolved with its host. The results indicate that BdAdV-1 belongs to
      the Mastadenovirus genus of the Adenoviridae family, however, it is clearly
      different from other adenoviruses, especially in the 3'-end of the viral genome.
      The high degree of sequence divergence suggests that BdAdV-1 should be considered
      as a novel species in the Mastadenovirus genus. The study also demonstrates the
      usefulness of high-throughput sequencing to obtain full-length genomes of
      genetically divergent viruses.

PMID- 28506840
TI  - Characterization of genome segments 2, 3 and 6 of epizootic hemorrhagic disease
      virus strains isolated in Japan in 1985-2013: Identification of their serotypes
      and geographical genetic types.
AB  - We characterized genome segments 2, 3 and 6 (Seg-2, Seg-3 and Seg-6) of 11
      Japanese strains of epizootic hemorrhagic disease (EHD) virus (EHDV) isolated in
      1985-2013. The Japanese strains were divisible into two groups based on
      phylogenetic analyses of the nucleotide sequences of Seg-2 and Seg-6. In both of
      the phylogenetic trees based on Seg-2 and Seg-6, seven of the 11 Japanese strains
      were grouped together with EHDV-2 and EHDV-7 strains, and the other four Japanese
      strains were grouped with EHDV-1 strains. The phylogenetic analysis of Seg-2
      among EHDV strains identified 10 of the 11 Japanese strains as EHDV-1, EHDV-2 or
      EHDV-7. The other Japanese strain, ON-4/B/98, isolated from an asymptomatic cow
      in 1998 was in the same group as the EHDV-2 and EHDV-7 strains in the
      phylogenetic trees based on Seg-2 and Seg-6, but the results suggested that the
      strain belongs to another serotype. We thus conducted a serum neutralization test
      to identify that serotype by using anti-EHDV-2 and anti-EHDV-7 rabbit sera. We
      observed that the ON-4/B/98 strain was not sufficiently neutralized by any of the
      antisera, which suggests that the strain could be assigned into a new serotype,
      tentatively named 'EHDV-10.' Sequences of Seg-3 were also determined, and all of
      the Japanese strains were grouped together with Australian strains, suggesting
      that the Japanese strains are a part of EHDV distributed in the Asia-Pacific
      region. The data obtained herein would be beneficial for the diagnosis and
      prevention of EHD in Japan and neighboring countries.

PMID- 28506839
TI  - Evolutionary relationships among protein lysine deacetylases of parasites causing
      neglected diseases.
AB  - The availability of the genomic data of diverse parasites provides an opportunity
      to identify new drug candidates against neglected tropical diseases affecting
      people worldwide. Histone modifying enzymes (HMEs) are potential candidates since
      they play key roles in the regulation of chromatin modifications, thus globally
      regulating gene expression. Furthermore, aberrant epigenetic states are often
      associated with human diseases, leading to great interest in HMEs as therapeutic
      targets. Our work focused on two families of protein lysine deacetylases (HDACs
      and sirtuins). First, we identified potential homologues in the predicted
      proteomes of selected taxa by using hidden Markov model profiles. Then, we
      reconstructed the evolutionary relationships of protein sequences by Bayesian
      inference and maximum likelihood method. In addition, we constructed homology
      models for five parasite HDACs to provide information for experimental validation
      and structure-based optimization of inhibitors. Our results showed that parasite
      genomes code for diverse HDACs and sirtuins. The evolutionary pattern of protein
      deacetylases with additional experimental data points to these enzymes as common
      drug targets among parasites. This work has improved the functional annotation of
      approximately 63% HDACs and 51% sirtuins in the selected taxa providing insights
      for experimental design. Homology models pointed out structural conservation and
      differences among parasite and human homologues and highlight potential
      candidates for further inhibitor development. Some of these parasite proteins are
      undergoing RNA interference or knockout analyses to validate the function of
      their corresponding genes. In the future, we will investigate the main functions
      performed by these proteins, related phenotypes, and their potential as
      therapeutic targets.

PMID- 28506841
TI  - Definition of a Critical Size Osteochondral Knee Defect and its Negative Effect
      on the Surrounding Articular Cartilage in the Rat.
AB  - BACKGROUND: Joint trauma is predisposing to the incidence of osteoarthritis (OA)
      of the knee. There is a limited knowledge on the impact of posttraumatic
      osteochondral defects on the whole joint. This study was designed to define a
      critical size osteochondral defect in the knee of rats and to investigate a
      possible association between osteochondral defects and degeneration of the
      surrounding joint surface. METHODS: Cylindrical osteochondral defects of
      different sizes were created in the knee joint of rats. The natural course of
      these lesions was studied by macroscopic observation, histology, and
      immunohistochemistry. Gene expression of the articular cartilage surrounding the
      defects in vivo and of articular chondrocytes cultured in vitro in IL1beta and
      fibroblast growth factor 2 (FGF2) supplemented media was evaluated by
      quantitative polymerase chain reaction (qPCR). RESULTS: In defects of 0.9 mm
      diameter, spontaneous joint surface healing was observed but also upward
      advancing of the subchondral bone plate at 16 weeks. Larger 1.4 mm diameter
      defects were critical size, not resulting in successful healing at any time
      point. Importantly, the articular cartilage surrounding the defects expressed
      FGF2 and IL1beta, but not ACAN and Col2. Chondrocytes cultured in IL1beta and
      FGF2 supplemented media lost the natural fibroblast growth factor receptors -
      FGFr1/FGFr3 balance and showed decreased viability. CONCLUSIONS: A critical size
      osteochondral defect was defined as 1.4 mm in diameter in rat. Subchondral bone
      plate advancement occured rapidly. The articular cartilage surrounding
      osteochondral defects showed catabolic activity with expression of IL1beta, FGF2
      and a disturbed FGFr1/FGFr3 balance, potentially initiating a process of early
      osteoarthritic disease.

PMID- 28506842
TI  - Diagnostic and prognostic value of delayed Gadolinium Enhanced Magnetic Resonance
      Imaging of Cartilage (dGEMRIC) in early osteoarthritis of the hip.
AB  - BACKGROUND: Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage
      (dGEMRIC) can detect glycosaminoglycan loss in the acetabular cartilage of
      asymptomatic individuals with cam morphology. The aims of this study were to
      explore the relationship between cam morphology and dGEMRIC values, and to
      explore whether baseline dGEMRIC can predict the development of radiographic hip
      osteoarthritis. METHODS: Prospective cohort (SibKids) study with clinical,
      radiographic, and MRI assessment at baseline and five-year follow-up (n = 34).
      The dGEMRIC values of cartilage regions were correlated with measures of cam
      morphology. Receiver operating characteristic (ROC) analysis was applied to
      baseline variables to predict radiographic loss of joint space width. RESULTS:
      Superolateral acetabular cartilage dGEMRIC values were significantly lower in
      participants with cam morphology (P < 0.001), defined as an alpha angle greater
      than 60 degrees . There was a negative correlation between alpha angle and the
      dGEMRIC value of adjacent acetabular cartilage. This relationship was strongest
      superoanteriorly (r = -0.697 P < 0.001). There was a positive correlation between
      baseline dGEMRIC and the magnitude of joint space width narrowing (r = 0.398 P =
      0.030). ROC analysis of combined baseline variables (positive impingement test,
      alpha angle, dGEMRIC ratio) gave an Area Under the Curve (AUC) of 0.75 for
      predicting joint space width narrowing greater than 0.5 mm within 5 years.
      CONCLUSIONS: The size and position of cam morphology determines the severity and
      location of progressive cartilage damage, supporting the biomechanical aetiology
      of femoroacetabular impingement. Baseline dGEMRIC is able to predict the
      development of radiographic osteoarthritis. Compositional MRI offers the
      potential to identify patients who may benefit from early intervention to prevent
      the development of osteoarthritis.

PMID- 28506844
TI  - Proarrhythmic risk assessment using conventional and new in vitro assays.
AB  - Drug-induced QT prolongation is a major safety issue in the drug discovery
      process. This study was conducted to assess the electrophysiological responses of
      four substances using established preclinical assays usually used in regulatory
      studies (hERG channel or Purkinje fiber action potential) and a new assay (human
      induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)-field
      potential). After acute exposure, moxifloxacin and dofetilide concentration
      dependently decreased IKr amplitude (IC50 values: 102 MUM and 40 nM,
      respectively) and lengthened action potential (100 MUM moxifloxacin: +23% and 10
      nM dofetilide: +18%) and field potential (300 MUM moxifloxacin: +76% and 10 nM
      dofetilide: +38%) durations. Dofetilide starting from 30 nM induced arrhythmia in
      hiPSC-CMs. Overnight application of pentamidine (10 and 100 MUM) and arsenic (1
      and 10 MUM) decreased IKr, whereas they were devoid of effects after acute
      application. Long-term pentamidine incubation showed a time- and concentration
      dependent effect on field potential duration. In conclusion, our data suggest
      that hiPSC-CMs represent a fully functional cellular electrophysiology model
      which may significantly improve the predictive validity of in vitro safety
      studies. Thereafter, lead candidates may be further investigated in patch-clamp
      assays for mechanistic studies on individual ionic channels or in a multicellular
      Purkinje fiber preparation for confirmatory studies on cardiac conduction.

PMID- 28506843
TI  - Longitudinal association between foot and ankle symptoms and worsening of
      symptomatic radiographic knee osteoarthritis: data from the osteoarthritis
      initiative.
AB  - OBJECTIVE: To assess whether foot and/or ankle symptoms are associated with an
      increased risk of worsening of knee pain and radiographic change in people with
      knee osteoarthritis (OA). METHODS: The presence and laterality of foot/ankle
      symptoms were recorded at baseline in 1368 participants from the Osteoarthritis
      Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity
      (measured using the Western Ontario and McMaster Universities Osteoarthritis
      Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width
      measured on X-ray were assessed yearly over the subsequent 4 years. Associations
      between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee
      pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using
      logistic regression. RESULTS: Foot/ankle symptoms in either foot/ankle
      significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI
      1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI
      1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and
      bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all
      associated with knee pain worsening in the follow up period. There was no
      association between foot/ankle symptoms and worsening of symptomatic radiographic
      knee OA. CONCLUSION: The presence of foot/ankle symptoms in people with
      symptomatic radiographic knee OA was associated with increased risk of knee pain
      worsening, but not worsening of symptomatic radiographic knee OA, over the
      subsequent 4 years. Future studies should investigate whether treatment of
      foot/ankle symptoms reduces the risk of knee pain worsening in people with knee
      OA.

PMID- 28506846
TI  - Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr
      cells.

PMID- 28506845
TI  - Ex Vivo Mesenchymal Precursor Cell-Expanded Cord Blood Transplantation after
      Reduced-Intensity Conditioning Regimens Improves Time to Neutrophil Recovery.
AB  - We previously showed the safety of using cord blood (CB) expanded ex vivo in
      cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative
      conditioning with faster recovery of neutrophils and platelets compared with
      historical controls. Herein, we report the transplantation outcomes of 27
      patients with hematologic cancers who received 1 CB unit expanded ex vivo with
      MPCs in addition to an unmanipulated CB (MPC group) after reduced-intensity
      conditioning (RIC). The results in this group were compared with 51 historical
      controls who received 2 unmanipulated CB units (control group). The analyses were
      stratified for 2 RIC treatment groups: (1) total body irradiation 200 cGy +
      cyclophosphamide + fludarabine) (TCF), and (2) fludarabine + melphalan  (FM).
      Coculture of CB with MPCs led to an expansion of total nucleated cells by a
      median factor of 12 and of CD34+ cells by a median factor of 49. In patients in
      whom engraftment occurred, the median time to neutrophil engraftment was 12 days
      in the MPC group, as compared with 16 days in controls (P = .02). The faster
      neutrophil engraftment was observed in both RIC groups. The cumulative incidence
      of neutrophil engraftment on day 26 was 75% with expansion versus 50% without
      expansion in patients who received FM as the RIC regimen (P = .03). Incidence of
      neutrophil engraftment was comparable in MPC and control groups if treated with
      TCF (82% versus 79%, P = .40). Transplantation of CB units expanded with MPCs is
      safe and effective with faster neutrophil engraftment even after RIC regimens.

PMID- 28506848
TI  - Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4
      inhibitor treatment.

PMID- 28506847
TI  - A short course of gamma-tocopherol mitigates LPS-induced inflammatory responses
      in humans ex vivo.

PMID- 28506849
TI  - Phase 2 to phase 3 clinical trial transitions: Reasons for success and failure in
      immunologic diseases.

PMID- 28506851
TI  - ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD)
      epitopes and can cause false-positive test results in patients with high anti-CCD
      IgE antibody levels.
AB  - BACKGROUND: Cross-reactive carbohydrate determinants (CCDs) in plants and insect
      venoms are a common cause of irrelevant positive test results during in vitro
      allergy diagnosis. We observed that some CCD-positive sera show nonspecific IgE
      binding even with CCD-free recombinant allergens when using the Phadia ImmunoCAP
      platform. OBJECTIVE: We investigated whether cellulose used as an allergen
      carrier in ImmunoCAP harbors residual N-glycans, causing nonspecific background
      binding in CCD-positive sera. METHODS: IgE binding to 6 samples of blank
      ImmunoCAPs coupled to either streptavidin (SA-CAP-1 or 2) or nonallergenic
      maltose-binding protein (MBP; MBP-CAP-1 to 4) and binding to a panel of 4
      recombinant allergens were compared in CCD-positive sera before and after
      inhibition with a CCD inhibitor (MUXF3-human serum albumin). RESULTS: Of 52 CCD
      positive sera (bromelain, 1.01-59.6 kilounits of antigen per liter [kUA/L])
      tested on SA-CAP-1, 35 (67%) showed IgE binding of greater than 0.35 kUA/L (0.41
      4.22 kUA/L). Among those with anti-CCD IgE levels of greater than 7.0 kUA/L, 90%
      (26/29) were positive. IgE binding to SA-CAP-1 correlated with IgE binding to
      bromelain (r = 0.68) and was completely abolished by serum preincubation with the
      CCD inhibitor (n = 15). Binding scores with SA-CAP-2 and MBP-CAP-1 to MBP-CAP-4
      were generally lower but strongly correlated with those of SA-CAP-1 and
      bromelain. IgE reactivity of 10 CCD-positive sera (14.0-52.5 kUA/L) with the
      recombinant allergens rPhl p 12, rFel d 1, rAra h 2, and rPru p 3 was positive to
      at least 1 allergen in 8 of 10 (0.36-1.63 kUA/L) and borderline in 2 of 10 (0.21
      0.25 kUA/L). Binding correlated with antibody binding to bromelain (r = 0.61) and
      to all blank ImmunoCAPs (r > 0.90) and could be completely blocked by the CCD
      inhibitor. Overall, mean background binding to cellulose CCDs corresponded to 2%
      to 3% of the reactivity seen with bromelain. CONCLUSIONS: Cellulose used as a
      solid-phase allergen carrier can contain varying amounts of CCDs sufficient to
      cause false-positive test results up to 2 kUA/L with nonglycosylated recombinant
      allergens in patients with high levels of anti-CCD IgE antibodies.

PMID- 28506852
TI  - Pulmonary inflammation in patients with chronic obstructive pulmonary disease
      with higher blood eosinophil counts.

PMID- 28506850
TI  - Neutrophil extracellular traps are associated with disease severity and
      microbiota diversity in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Neutrophil extracellular traps (NETs) have been observed in the
      airway in patients with chronic obstructive pulmonary disease (COPD), but their
      clinical and pathophysiologic implications have not been defined. OBJECTIVE: We
      sought to determine whether NETs are associated with disease severity in patients
      with COPD and how they are associated with microbiota composition and airway
      neutrophil function. METHODS: NET protein complexes (DNA-elastase and histone
      elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in
      soluble sputum and serum from patients with COPD during periods of disease
      stability and during exacerbations and compared with clinical measures of disease
      severity and the sputum microbiome. Peripheral blood and airway neutrophil
      function were evaluated by means of flow cytometry ex vivo and experimentally
      after stimulation of NET formation. RESULTS: Sputum NET complexes were associated
      with the severity of COPD evaluated by using the composite Global Initiative for
      Obstructive Lung Disease scale (P < .0001). This relationship was due to modest
      correlations between NET complexes and FEV1, symptoms evaluated by using the COPD
      assessment test, and higher levels of NET complexes in patients with frequent
      exacerbations (P = .002). Microbiota composition was heterogeneous, but there was
      a correlation between NET complexes and both microbiota diversity (P = .009) and
      dominance of Haemophilus species operational taxonomic units (P = .01). Ex vivo
      airway neutrophil phagocytosis of bacteria was reduced in patients with increased
      sputum NET complexes. Consistent results were observed regardless of the method
      of quantifying sputum NETs. Failure of phagocytosis could be induced
      experimentally by incubating healthy control neutrophils with soluble sputum from
      patients with COPD. CONCLUSION: NET formation is increased in patients with
      severe COPD and associated with more frequent exacerbations and a loss of
      microbiota diversity.

PMID- 28506853
TI  - Expression of semaphorin 3E is suppressed in severe asthma.

PMID- 28506854
TI  - Long-Term Safety and Efficacy of Solifenacin in Children and Adolescents with
      Overactive Bladder.
AB  - PURPOSE: We evaluated the long-term safety and efficacy of once daily oral
      solifenacin suspension in children (5 to less than 12 years old) and adolescents
      (12 to less than 18 years old) with overactive bladder. MATERIALS AND METHODS: We
      conducted a 40-week, open label extension of a 12-week double-blind, placebo
      controlled trial. Outcome measures included incidence and severity of adverse
      events (primary end point), laboratory variables, vital signs, 12-lead
      electrocardiogram, post-void residual volume, and change from baseline to end of
      treatment in mean number of micturitions and incontinence episodes per 24 hours,
      number of incontinence-free days per 7 days and number of grade 3 or 4 urgency
      episodes per 24 hours (adolescents only). RESULTS: A total of 119 children and 29
      adolescents were enrolled in the study. The incidence of drug related treatment
      emergent adverse events was 34.7% (children) and 37.9% (adolescents), the most
      common of which were constipation (11.9%), electrocardiogram QT prolonged (8.5%)
      and dry mouth (4.2%) in children, and electrocardiogram QT prolonged (13.8%) and
      nausea (6.9%) in adolescents. Adverse events resulted in 10.2% (children) and
      13.8% (adolescents) of participants discontinuing treatment. There were no cases
      of urinary retention or increases in post-void residual volume and no clinically
      relevant changes in laboratory variables or vital signs. Two cases of dizziness
      but no other central nervous system drug related treatment emergent adverse
      events were reported. Improvements in all efficacy parameters and grade 3 or 4
      urgency episodes observed by 3 weeks were further improved and/or maintained
      during the study. CONCLUSIONS: Once daily solifenacin oral suspension was well
      tolerated for up to 52 weeks in children 5 to less than 12 years old and
      adolescents 12 to less than 18 years old diagnosed with overactive bladder, with
      constipation and electrocardiogram QT prolonged as the most common adverse
      reactions, respectively. Improvements in efficacy at 3 weeks were sustained
      during the study.

PMID- 28506855
TI  - Rates and Risk Factors for Opioid Dependence and Overdose after Urological
      Surgery.
AB  - PURPOSE: Effective pain management is a critical component of the perioperative
      process with opioids representing a mainstay of therapy. The opioid epidemic is a
      growing concern in the United States. The goal of this study was to quantify the
      risk of opioid dependence or overdose among patients undergoing urological
      surgery and to identify risk factors of opioid dependence or overdose. MATERIALS
      AND METHODS: We retrospectively reviewed data on urological surgery from 2007 to
      2011. Data sources included the HCUP (Healthcare Cost and Utilization Project)
      inpatient, ambulatory surgery and emergency department data sets. Outcomes of
      postoperative opioid dependence and overdose were identified by previously
      validated ICD-9 codes. Multivariable logistic regression adjusted for surgical
      procedure was performed to identify predictors of opioid dependence or overdose
      following urological surgery. RESULTS: Overall 675,527 patients underwent
      urological surgery, of whom 0.09% were diagnosed with opioid dependence or
      overdose. Patients in whom opioid dependence or overdose developed were younger
      (median age 51 vs 62 years), carried nonprivate insurance (69.6% vs 66%),
      underwent an inpatient procedure (81.0% vs 42.4%) and had a longer length of stay
      (median 3 vs 0 days) and a history of depression (14.4% vs 3.4%) or chronic
      obstructive pulmonary disease (20.3% vs 8.9%, all p <0.001). On adjusted
      multivariable analysis these factors remained independent risk factors for opioid
      dependence or overdose. CONCLUSIONS: Postoperative opioid dependence or overdose
      affects 1 of 1,111 urological surgery patients. Risk factors for opioid
      dependence or overdose included younger age, inpatient surgery and increasing
      hospitalization duration, baseline depression, tobacco use and chronic
      obstructive pulmonary disease as well as insurance provider, including Medicaid,
      Medicare (age less than 65 years) and noninsured status.

PMID- 28506856
TI  - Bariatric surgery revisions and private health insurance.
AB  - OBJECTIVE: To identify: 1. The percentage of bariatric procedures that are
      revisions; 2. What proportion of bariatric revision procedures in public
      hospitals are for patients whose primary weight loss procedure occurred in a
      private hospital; 3. The age, sex and level of socioeconomic disadvantage of
      patients needing revisions. METHODS: An analysis of patient level admission data
      from the Integrated South Australian Activity Collection (ISAAC) was performed.
      Data were collected on all revisions for weight loss related procedures at all
      South Australian public and private hospitals, between 2000-2015 using the ISAAC
      codes for revision procedures. RESULTS: 12,606 bariatric procedures occurred in
      hospitals; ~27% of which represent a revision (n=3366). Of these revisions, ~82%
      occurred in a private hospital (n=2771), and ~18% occurred in a public hospital
      (n=595). Of the 595 revisions in a public hospital, 51% of patients had their
      original bariatric procedure performed in a private hospital. The majority of
      patients who had a revision procedure are female (>=82%) with a mean age of ~45.
      Individuals from the lowest 2 IRSD quintiles were over-represented for public
      hospital revisions and primary bariatric procedures. CONCLUSION: Further
      investigation is needed to identify: 1. Why 27% of bariatric procedures are
      revisions; 2. Why at least 51% of revisions in public hospitals are on patients
      whose original primary bariatric procedure was done in a private hospital; 3. The
      impact that revision procedures in public hospitals, particularly for originally
      private weight loss procedures, is having on public hospital wait times; 4. The
      impact of socioeconomic disadvantage on weight loss procedure outcomes.

PMID- 28506857
TI  - FOXK2, regulted by miR-1271-5p, promotes cell growth and indicates unfavorable
      prognosis in hepatocellular carcinoma.
AB  - The forkhead transcription factor FOXK2 has been implicated in the progression of
      human cancers, but its role and clinical significance in hepatocellular carcinoma
      (HCC) have not been explored. Here we showed that FOXK2 expression was increased
      and associated with tumor size, TNM stage and vascular invasion. High FOXK2
      expression was correlated with poor overall and disease-free survival in two
      independent cohorts consisting of 864 patients with HCC. The prognostic value of
      FOXK2 was validated by stratified survival analyses in subgroups difined by
      factors contributing to worse survival. Multivariate Cox regression model
      revealed that FOXK2 served as an independent factor for overall survival. The
      FOXK2 expression was reversely connected with miR-1271-5p in clinical samples. Re
      introduction of miR-1271 decreased FOXK2 at both mRNA and protein levels.
      Luciferase assay confirmed that FOXK2 was a direct target of miR-1271 in HCC
      cells. Overexpression of FOXK2 enhanced the cell growth and migration, whereas
      FOXK2 silence resulted in the opposite phenotypes. Further studies demonstrated
      that FOXK2 exerted oncogenic activity via activation of PI3K/AKT signaling
      pathway. Collectively, our data suggest FOXK2 as an oncogene and a promising
      prognostic biomarker in HCC. Targeting the newly identified miR-1271/FOXK2/AKT
      axis may represent a potential strategy for HCC intervention.

PMID- 28506858
TI  - Accuracy of 1H magnetic resonance spectroscopy for quantification of 2
      hydroxyglutarate using linear combination and J-difference editing at 9.4T.
AB  - Non-invasive detection of 2-hydroxyglutarate (2HG) by magnetic resonance
      spectroscopy is attractive since it is related to tumor metabolism. Here, we
      compare the detection accuracy of 2HG in a controlled phantom setting via widely
      used localized spectroscopy sequences quantified by linear combination of
      metabolite signals vs. a more complex approach applying a J-difference editing
      technique at 9.4T. Different phantoms, comprised out of a concentration series of
      2HG and overlapping brain metabolites, were measured with an optimized point
      resolved-spectroscopy sequence (PRESS) and an in-house developed J-difference
      editing sequence. The acquired spectra were post-processed with LCModel and a
      simulated metabolite set (PRESS) or with a quantification formula for J
      difference editing. Linear regression analysis demonstrated a high correlation of
      real 2HG values with those measured with the PRESS method (adjusted R-squared:
      0.700, p<0.001) as well as with those measured with the J-difference editing
      method (adjusted R-squared: 0.908, p<0.001). The regression model with the J
      difference editing method however had a significantly higher explanatory value
      over the regression model with the PRESS method (p<0.0001). Moreover, with J
      difference editing 2HG was discernible down to 1mM, whereas with the PRESS method
      2HG values were not discernable below 2mM and with higher systematic errors,
      particularly in phantoms with high concentrations of N-acetyl-asparate (NAA) and
      glutamate (Glu). In summary, quantification of 2HG with linear combination of
      metabolite signals shows high systematic errors particularly at low 2HG
      concentration and high concentration of confounding metabolites such as NAA and
      Glu. In contrast, J-difference editing offers a more accurate quantification even
      at low 2HG concentrations, which outweighs the downsides of longer measurement
      time and more complex postprocessing.

PMID- 28506859
TI  - The Obstructed Bladder: Expression of Collagen, Matrix Metalloproteinases,
      Muscarinic Receptors, and Angiogenic and Neurotrophic Factors in Patients With
      Benign Prostatic Hyperplasia.
AB  - OBJECTIVE: To evaluate the gene expression of collagen, matrix metalloproteinases
      (MMPs) and inhibitors, cholinergic muscarinic receptors (CHRMs), and angiogenic
      and nerve growth factors (NGFs) in the bladder of patients with bladder outlet
      obstruction caused by benign prostatic hyperplasia (BPH). METHODS: We analyzed
      bladder specimens from 43 patients with obstructive BPH undergoing transurethral
      resection of the prostate as compared to 10 age-matched controls with an
      International Prostatic Symptom Score of <8 and a prostate volume of <30 g. A
      bladder biopsy was performed for relative gene expression analysis with
      quantitative real-time polymerase chain reaction of collagens I and III, MMP-1,
      MMP-2, and MMP-9; tissue inhibitors of metalloproteinases (TIMPs) TIMP-1, TIMP-2,
      and reversion-inducing cysteine-rich protein with kazal motifs (RECK); CHRM2 and
      CHRM3; VEGF and CD105; and NGF and nerve growth factor receptor (NGFr). RESULTS:
      Patients with bladder outlet obstruction presented a statistically significant
      overexpression of collagens I and III, VEGF, CHRM2, and CHRM3. CD105, MMP-9, and
      TIMP-1 were underexpressed. Expressions of NGF, NGFr, MMP-1, MMP-2, TIMP-2, and
      RECK were heterogeneous. CHRM2 and CHRM3 were overexpressed in patients with
      persistent detrusor overactivity. Smokers presented an upregulation of NGFr and
      VEGF; dyslipidemic patients had an overexpression of NGFr. CONCLUSION: Bladder
      upregulation of collagens I and III on transcriptional level appears to be
      relevant in BPH. Muscarinic receptors CHRM2 and CHRM3 are also overexpressed,
      more so in patients with persistent detrusor overactivity. Upregulation of VEGF
      and NGFr, particularly in subjects with risk factors for atherosclerosis,
      reinforces the role of ischemia in BPH-induced modifications of the bladder.

PMID- 28506860
TI  - Characterization of Late Recurrence After Radical Cystectomy in a Large
      Multicenter Cohort of Bladder Cancer Patients.
AB  - OBJECTIVE: To investigate the characteristics and outcomes of late recurrence
      (LR) in patients with bladder cancer (BCa) treated with radical cystectomy (RC)
      and to identify clinicopathologic predictors of LR and postrecurrence survival.
      MATERIALS AND METHODS: This multicenter study included 1652 BCa patients. LR was
      defined as occurring more than 5 years after RC. Differences in postrecurrence
      overall survival according to the timing of disease recurrence and the location
      of recurrence were calculated using the log-rank test. A logistic regression
      model was used to identify predictors of LR, and Cox regression models were used
      to evaluate variables associated with postrecurrence overall survival (OS).
      RESULTS: Overall, 548 patients experienced disease recurrence. Of these, 67
      patients (12.2%) experienced LR, with a median time to recurrence of 86 months
      (interquartile range 70.5-107.2). LR was more likely to be located in the
      urothelium (P = .005). On multivariable analysis, younger age (P = .008) and non
      organ confined disease (P = .03) were found to be predictors of LR.
      Postrecurrence 5-year OS was worse in patients who experienced early recurrence
      compared with those with LR (12% vs 25%, P = .02) and in those with nonurothelial
      recurrence compared to those with disease recurrence in the remaining urothelium
      (12% vs 51%, P < .001). Older age (P < .001), non-organ confined disease at RC (P
      = .02), and nonurothelial recurrence site (P = .002) were independently
      associated with postrecurrence OS. CONCLUSION: LR after RC is an uncommon but non
      negligible event that harbors unique characteristics. LR is associated with
      better OS compared to early recurrence. Our findings reinforce the need for
      lifelong follow-up of BCa patients after RC.

PMID- 28506861
TI  - Do Urinary Leakage Circumstances in Women With Urinary Incontinence Correlate
      With Physician Diagnosis and Urodynamic Results? A Questionnaire Validation
      Study.
AB  - OBJECTIVE: To investigate if leakage circumstances collected using the Urinary
      Leakage Circumstances Questionnaire (ULCQ) are correlated with physician
      diagnosis and urodynamic results and resolve after surgery. MATERIALS AND
      METHODS: The ULCQ was developed to investigate leakage circumstances encountered
      by women with incontinence. Women completed both the ULCQ and the International
      Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form before
      clinical and urodynamic examination. Those who underwent a suburethral sling
      procedure completed both questionnaires postoperatively. We performed a principal
      component analysis and evaluated the questionnaire's external properties
      including construct validity and responsiveness. RESULTS: One hundred and eighty
      six women were included in the validation phase, and 168 underwent suburethral
      sling procedure. Mean postoperative follow-up was 51 months. Principal component
      analysis identified 4 dimensions from the 23 leakage circumstances listed in the
      ULCQ: effort, stimulation, postural, and intercourse; the internal consistency of
      each dimension was excellent (Cronbach alpha: 0.87, 0.86, 0.82, and 0.79,
      respectively). Effort (+0.39), stimulation (+0.24), and postural (+0.47)
      dimensions were correlated with the International Consultation on Incontinence
      Questionnaire-Urinary Incontinence Short Form score; the effort dimension was
      correlated with greater stress incontinence severity assessed by the physician;
      the stimulation dimension with urgency and urge incontinence severity assessed by
      the physician, and with lower volumes during cystometry; and the postural
      dimension with higher age and lower urethral closure pressure. Each dimension
      recorded a significant improvement after surgery, with the largest effect size
      for effort dimension (2.29 [confidence interval 95%: 1.96-2.62]). CONCLUSION: The
      ULCQ is a useful tool for investigating female urinary incontinence and detecting
      changes after surgery.

PMID- 28506862
TI  - A Relevant Midterm (12 Months) Placebo Effect on Lower Urinary Tract Symptoms and
      Maximum Flow Rate in Male Lower Urinary Tract Symptom and Benign Prostatic
      Hyperplasia-A Meta-analysis.
AB  - OBJECTIVE: To assess the mid- to long-term placebo effect of the medical and
      instrumental management of male lower urinary tract symptoms. This is generally a
      long-term treatment strategy. Therefore, knowledge on the mid- to long-term
      placebo effect is of considerable interest. The paucity of data on this topic
      prompted us to investigate this issue in a meta-analysis. METHODS: All randomized
      controlled trials (RCTs) with the indication of benign prostatic hyperplasia and
      lower urinary tract symptoms containing a placebo- or sham treatment arm and with
      a follow-up of 12 months were eligible. The 12-month effect of placebo or sham
      treatment on the International Prostate Symptom Score (the quality-of-life
      question was not analyzed herein) and the American Urological Association Symptom
      Score and on the maximum flow rate was quantified. RESULTS: A total of 25 RCTs
      with 10.587 patients were eligible. Twenty-three studies were placebo controlled
      (plant extracts: n = 4, 5alpha-reductase inhibitors [5ARIs]: n = 9, alpha
      blocker: n = 5, combination therapy of 5ARI and alpha-blocker: n = 3, and
      intraprostatic botulinum toxin A injection: n = 2), and 2 RCTs with transurethral
      microwave thermotherapy (TUMT) had a sham treatment arm. At 12 months, the mean
      International Prostate Symptom Score improved by a mean of 4.4 points under
      placebo or sham treatment with a range of 0.7-6.8 points: plant extracts, -3.6;
      5ARI, -3.4; alpha-blocker, -4.3; combination therapy, -4.3; botulinum toxin A, 
      3.9; and TUMT, -6.8. The mean maximum flow rate improvement at 12 months under
      placebo or sham was not relevant (+0.8 mL/s), yet there were remarkable
      differences between trials: plant extracts, -0.3 mL/s; 5ARI, +0.8 mL/s; alpha
      blocker, +1.1 mL/s; combination therapy, +1.4 mL/s; and TUMT, +1.0 mL/s.
      CONCLUSION: This meta-analysis demonstrates the mid-term placebo effect on lower
      urinary tract function, particularly concerning subjective improvement. The
      degree of the placebo effect varies considerable between studies even at 12
      months.

PMID- 28506863
TI  - The Null-Test for peptide identification algorithm in Shotgun proteomics.
AB  - : The present research proposed general evaluation strategy named Null-Test for
      peptide identification algorithm in Shotgun proteomics. The Null-Test method
      based on random matching can be utilized to check whether the algorithm has a
      tendency to make a mistake or has potential bugs, faultiness, errors etc., and to
      validate the reliability of the identification algorithm. Unfortunately, none of
      the five famous identification software could pass the most stringent Null-Test.
      PatternLab had good performance in both Null-Test and routine search by making a
      good control on the overfitting with sound design. The fuzzy logics based method
      presented as another candidate strategy could pass the Null-Test and has
      competitive efficiency in peptide identification. Filtering the results by
      appropriate FDR would increase the number of discoveries in an experiment, at the
      cost of losing control of Type I errors. Thus, it is necessary to utilize some
      more stringent criteria when someone wants to design or analyze an
      algorithm/software. The more stringent criteria will facilitate the discovery of
      latent bugs, faultiness, errors etc. in the algorithm/software. It would be
      recommended to utilize independent search combining random database with
      statistics theorem to estimate the accurate FDR of the identified results.
      BIOLOGICAL SIGNIFICANCE: In the past decades, considerable effort has been
      devoted to developing a sensitive algorithm for peptide identification in Shotgun
      proteomics. However, little attention has been paid to controlling the
      reliability of the identification algorithm at the design stage. The Null-Test
      based on random matching can be utilized to check whether the algorithm has a
      tendency to make a mistake or has potential bugs, faultiness, errors etc.
      However, it turns out that none of the five famous identification software could
      pass the most stringent Null-Test in the present study, which should be taken
      into account seriously. Accordingly, a candidate strategy based on fuzzy logics
      has been demonstrated the possibility that an identification algorithm can pass
      the Null-Test. PatternLab shows that earlier control on overfitting is valuable
      for designing an efficient algorithm.

PMID- 28506864
TI  - Asking the right questions.

PMID- 28506865
TI  - Protocol-driven neurological prognostication and withdrawal of life-sustaining
      therapy after cardiac arrest and targeted temperature management.
AB  - BACKGROUND: Brain injury is reportedly the main cause of death for patients
      resuscitated after out-of-hospital cardiac arrest (OHCA). However, the majority
      may actually die following withdrawal of life-sustaining therapy (WLST) with a
      presumption of poor neurological recovery. We investigated how the protocol for
      neurological prognostication was used and how related treatment recommendations
      might have affected WLST decision-making and outcome after OHCA in the targeted
      temperature management (TTM) trial. METHODS: Analyses of prospectively recorded
      data: details of neurological prognostication; recommended level-of-care; WLST
      decisions; presumed cause of death; and cerebral performance category (CPC) 6
      months following randomization. RESULTS: Of 939 patients, 452 (48%) woke and 139
      (15%) died, mostly for non-neurological reasons, before a scheduled time point
      for neurological prognostication (72h after the end of TTM). Three hundred and
      thirteen (33%) unconscious patients underwent prognostication at a median 117
      (IQR 93-137) hours after arrest. Thirty-three (3%) unconscious patients were not
      neurologically prognosticated and for 2 patients (1%) data were missing. Related
      care recommendations were: continue in 117 (37%); not escalate in 55 (18%); and
      withdraw in 141 (45%). WLST eventually occurred in 196 (63%) at median day 6 (IQR
      5-8). At 6 months, only 2 patients with WLST were alive and 248 (79%) of
      prognosticated patients had died. There were significant differences in time to
      WLST and death after the different recommendations (log rank <0.001). CONCLUSION:
      Delayed prognostication was relevant for a minority of patients and related to
      subsequent decisions on level-of-care with effects on ICU length-of-stay,
      survival time and outcome.

PMID- 28506866
TI  - Non-maturational covariates for dynamic systems pharmacology models in neonates,
      infants, and children: Filling the gaps beyond developmental pharmacology.
AB  - Pharmacokinetics and -dynamics show important changes throughout childhood.
      Studies on the different maturational processes that influence developmental
      pharmacology have been used to create population PK/PD models that can yield
      individualized pediatric drug dosages. These models were subsequently translated
      to semi-physiologically or physiology-based PK (PBPK) models that support
      predictions in pediatric patient cohorts and other special populations. Although
      these translational efforts are crucial, these models should be further improved
      towards individual patient predictions by including knowledge on non-maturational
      covariates. These efforts are needed to ultimately get to systems pharmacology
      models for children. These models take developmental changes relating to the
      pediatric dynamical system into account but also other aspects that may be of
      importance such as abnormal body composition, pharmacogenetics, critical illness
      and inflammatory status.

PMID- 28506867
TI  - Towards personalized treatment of pain using a quantitative systems pharmacology
      approach.
AB  - Pain is a complex biopsychosocial phenomenon of which the intensity, location and
      duration depends on various underlying components. Treatment of pain is
      associated with considerable inter-individual variability, and as such, requires
      a personalized approach. However, a priori prediction of optimal analgesic
      treatment for individual patients is still challenging. Another challenge is the
      assessment and treatment of pain in patients unable to self-report pain. In this
      mini-review, we first provide a brief overview of the various components
      underlying pain, and their associated biomarkers. These include clinical,
      psychosocial, neurophysiological, and biochemical components. We then discuss the
      use of empirical and mechanism-based pharmacokinetic-pharmacodynamic modelling to
      support personalized treatment of pain. Finally, we propose how these concepts
      can be extended to a quantitative systems pharmacology (QSP) approach that
      integrates the components of clinical pain and treatment response. This
      integrative approach can support predictions of optimal pharmacotherapy of pain,
      compared with approaches that focus on single components of pain. Moreover,
      combination of QSP modelling with state-of-the-art metabolomics approaches may
      offer unique possibilities to identify novel pain biomarkers. Such biomarkers
      could support both the personalized treatment of pain and translational drug
      development of novel analgesic agents. In conclusion, a QSP approach will likely
      improve our ability to predict pain and treatment response, paving the way for
      personalized treatment of pain.

PMID- 28506868
TI  - Drug-disease modeling in the pharmaceutical industry - where mechanistic systems
      pharmacology and statistical pharmacometrics meet.
AB  - Modeling & simulation (M&S) methodologies are established quantitative tools,
      which have proven to be useful in supporting the research, development (R&D),
      regulatory approval, and marketing of novel therapeutics. Applications of M&S
      help design efficient studies and interpret their results in context of all
      available data and knowledge to enable effective decision-making during the R&D
      process. In this mini-review, we focus on two sets of modeling approaches:
      population-based models, which are well-established within the pharmaceutical
      industry today, and fall under the discipline of clinical pharmacometrics (PMX);
      and systems dynamics models, which encompass a range of models of (patho
      )physiology amenable to pharmacological intervention, of signaling pathways in
      biology, and of substance distribution in the body (today known as
      physiologically-based pharmacokinetic models) - which today may be collectively
      referred to as quantitative systems pharmacology models (QSP). We next describe
      the convergence - or rather selected integration - of PMX and QSP approaches into
      'middle-out' drug-disease models, which retain selected mechanistic aspects,
      while remaining parsimonious, fit-for-purpose, and able to address variability
      and the testing of covariates. We further propose development opportunities for
      drug-disease systems models, to increase their utility and applicability
      throughout the preclinical and clinical spectrum of pharmaceutical R&D.

PMID- 28506869
TI  - Model-based clinical dose optimization for phenobarbital in neonates: An
      illustration of the importance of data sharing and external validation.
AB  - BACKGROUND: Particularly in the pediatric clinical pharmacology field, data
      sharing offers the possibility of making the most of all available data. In this
      study, we utilize previously collected therapeutic drug monitoring (TDM) data of
      term and preterm newborns to develop a population pharmacokinetic model for
      phenobarbital. We externally validate the model using prospective phenobarbital
      data from an ongoing pharmacokinetic study in preterm neonates. METHODS: TDM data
      from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2.7 (0.45
      4.5) kg; postnatal age (PNA): 4.5 (0-22) days) contained information on dosage
      histories, concentration and covariate data (including birth weight, actual
      weight, post-natal age (PNA), postmenstrual age, GA, sex, liver and kidney
      function, APGAR-score). Model development was carried out using NONMEM(r) 7.3.
      After assessment of model fit, the model was validated using data of 17 neonates
      included in the DINO (Drug dosage Improvement in NeOnates)-study. RESULTS:
      Modelling of 229 plasma concentrations, ranging from 3.2 to 75.2mg/L, resulted in
      a one compartment model for phenobarbital. Clearance (CL) and volume (Vd) for a
      child with a birthweight of 2.6kg at PNA day 4.5 was 0.0091L/h (9%) and 2.38L
      (5%), respectively. Birthweight and PNA were the best predictors for CL
      maturation, increasing CL by 36.7% per kg birthweight and 5.3% per postnatal day
      of living, respectively. The best predictor for the increase in Vd was actual
      bodyweight (0.31L/kg). External validation showed that the model can adequately
      predict the pharmacokinetics in a prospective study. CONCLUSION: Data-sharing can
      help to successfully develop and validate population pharmacokinetic models in
      neonates. From the results it seems that both PNA and bodyweight are required to
      guide dosing of phenobarbital in term and preterm neonates.

PMID- 28506870
TI  - Development of solid SEDDS, VII: Effect of pore size of silica on drug release
      from adsorbed self-emulsifying lipid-based formulations.
AB  - PURPOSE: Lipid-based self-emulsifying drug delivery systems (SEDDS) are usually
      liquids, and they can be converted into solid dosage forms by adsorbing onto
      silicates. However, most commercially available silicates are mesoporous with
      small pore sizes of 1 to 50nm that lead to incomplete emulsification of SEDDS
      inside the pores and thus incomplete drug release. The objective of this study
      was to investigate the impact of silica pore size on the extent of drug release
      from SEDDS solidified by adsorbing onto macroporous silicas with different pore
      sizes. METHODS: Silicas with average pore sizes of approx. 150nm, 500nm and 5MUm
      were synthesized using the colloidal crystal templating method. A model poorly
      water-soluble drug, probucol, was dissolved in liquid SEDDS containing different
      lipid to surfactant ratios, and the formulations were then adsorbed onto equal
      weights of silicas (1:1 w/w ratio). Drug release from freshly prepared
      formulations and after storing at 40 degrees C/60% RH for up to 6months was
      studied using a modified USP type 2 method with mini paddles and 50mL of 0.01M
      HCl (pH~2) at 37 degrees C. Drug release was also studied similarly from silicas
      that were precoated with PVP K-30 at 5, 10, 20 and 30% w/w levels before
      adsorption of SEDDS. RESULTS: Freshly prepared formulations containing relatively
      higher lipid:surfactant ratio of 7:3% w/w exhibited 17, 40 and 60% drug release
      from uncoated (neat) silicas with pore sizes of 150nm, 500nm and 5MUm,
      respectively, while the more hydrophilic formulations containing 3:7 w/w
      lipid:surfactant ratio had, respectively, 50, 65 and 85% drug release. No
      decrease in drug release was observed when the formulations were exposed to 40
      degrees C/60% RH for up to 6months. When the silicas were precoated with 20% PVP,
      the drug release was almost complete (>80%), which remained unchanged even after
      6months of storage irrespective of the composition of adsorbed liquid SEDDS.
      CONCLUSIONS: Both pore size and composition of SEDDS had major impacts on drug
      release from silicas. Increased drug release was observed with the increase in
      pore size of silicas and hydrophilicity of formulations. Since the silicas
      synthesized were macroporous with no mesopores present, there was no decrease in
      drug release upon storage. Complete drug release was observed when silicas were
      precoated with PVP as it increased the penetration of water into the pores.

PMID- 28506871
TI  - The role of hyaluronan as a drug carrier to enhance the bioavailability of
      extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a
      model case.
AB  - The aim of this work was to obtain information concerning the properties of
      ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the
      factors that determine the onset, intensity and duration of the
      pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium
      hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and
      presented a counterionic condensation higher than 75%. For comparison a similar
      complex obtained with hyaluronic acid (HyH) was also prepared. Although the
      viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro
      release of TM from both complexes showed a similar extended drug release profile
      (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular
      pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM
      complex exhibited attractive bioavailability properties in the aqueous humor (AUC
      and Cmax significantly higher and later Tmax) compared to commercial TM eye
      drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h)
      and a more intense hypotensive activity was observed after instillation of a drop
      of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer
      pre-corneal residence times (400%) observed with HyNa-TM complex. No significant
      changes in rabbit transcorneal permeation were detected upon complexation. These
      results demonstrate that the ability of HyNa to modulate TM release, together
      with its mucoadhesiveness related to the viscosity, affected both the
      pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a
      potentially useful carrier for ocular drug delivery, which could improve the TM
      efficacy and reduce the frequency of administration to improve patient
      compliance.

PMID- 28506872
TI  - Unreliability of putative fMRI biomarkers during emotional face processing.
AB  - There is considerable need to develop tailored approaches to psychiatric
      treatment. Numerous researchers have proposed using functional magnetic resonance
      imaging (fMRI) biomarkers to predict therapeutic response, in particular by
      measuring task-evoked subgenual anterior cingulate (sgACC) and amygdala
      activation in mood and anxiety disorders. Translating this to the clinic relies
      on the assumption that blood-oxygen-level dependent (BOLD) responses in these
      regions are stable within individuals. To test this assumption, we scanned a
      group of 29 volunteers twice (mean test-retest interval=14.3 days) and calculated
      the within-subject reliability of the amplitude of the amygdalae and sgACC BOLD
      responses to emotional faces using three paradigms: emotion identification;
      emotion matching; and gender classification. We also calculated the reliability
      of activation in a control region, the right fusiform face area (FFA). All three
      tasks elicited robust group activations in the amygdalae and sgACC (which changed
      little on average over scanning sessions), but within-subject reliability was
      surprisingly low, despite excellent reliability in the control right FFA region.
      Our findings demonstrate low statistical reliability of two important putative
      treatment biomarkers in mood and anxiety disorders.

PMID- 28506874
TI  - Impact of acquisition and analysis strategies on cortical depth-dependent fMRI.
AB  - Functional MRI at ultra-high magnetic fields (>= 7T) provides the opportunity to
      probe columnar and laminar processing in the human brain in vivo at sub
      millimeter spatial scales. However, fMRI data only indirectly reflects the
      neuronal laminar profile due to a bias to ascending and pial veins inherent in
      gradient- and spin-echo BOLD fMRI. In addition, accurate delineation of the
      cortical depths is difficult, due to the relatively large voxel sizes and lack of
      sufficient tissue contrast in the functional images. In conventional depth
      dependent fMRI studies, anatomical and functional data are acquired with
      different image read-out modules, the fMRI data are distortion-corrected and
      vascular biases are accounted for by subtracting the depth-dependent activation
      profiles of different stimulus conditions. In this study, using high-resolution
      gradient-echo fMRI data (0.7 mm isotropic) of the human visual cortex, we propose
      instead, that depth-dependent functional information is best preserved if data
      analysis is performed in the original functional data space. To achieve this, we
      acquired anatomical images with high tissue contrast and similar distortion to
      the functional images using multiple inversion-recovery time EPI, thereby
      eliminating the need to un-distort the fMRI data. We demonstrate higher spatial
      accuracy for the cortical layer definitions of this approach as compared to the
      more conventional approach using MP2RAGE anatomy. In addition, we provide
      theoretical arguments and empirical evidence that vascular biases can be better
      accounted for using division instead of subtraction of the depth-dependent
      profiles. Finally, we show that the hemodynamic response of grey matter has
      relatively stronger post-stimulus undershoot than the pial vein voxels. In
      summary, we show that the choice of fMRI data acquisition and processing can
      impact observable differences in the cortical depth profiles and present evidence
      that cortical depth-dependent modulation of the BOLD signal can be resolved using
      gradient-echo imaging.

PMID- 28506873
TI  - Transcranial manganese delivery for neuronal tract tracing using MEMRI.
AB  - There has been a growing interest in the use of manganese-enhanced MRI (MEMRI)
      for neuronal tract tracing in mammals, especially in rodents. For this MEMRI
      application, manganese solutions are usually directly injected into specific
      brain regions. Recently it was reported that manganese ions can diffuse through
      intact rat skull. Here the local manganese concentrations in the brain tissue
      after transcranial manganese application were quantified and the effectiveness of
      tracing from the area under the skull where delivery occurred was determined. It
      was established that transcranially applied manganese yields brain tissue
      enhancement dependent on the location of application on the skull and that
      manganese that enters the brain transcranially can trace to deeper brain areas.

PMID- 28506875
TI  - Deubiquitinase USP33 is negatively regulated by beta-TrCP through ubiquitin
      dependent proteolysis.
AB  - Ubiquitin-mediated proteolysis regulates cellular levels of various proteins, and
      therefore plays important roles in controlling cell signaling and disease
      progression. The Skp1-Cul1-F-box ubiquitin ligase beta-TrCP is recognized as an
      important negative regulator for numerous key signaling proteins. Recently, the
      deubiquitinases (DUBs) have turned out to be essential to regulate signaling
      pathways related to human diseases. However, whether beta-TrCP is able to
      regulate the deubiquitinase family members remains largely unexplored. Here, we
      found that beta-TrCP downregulated cellular levels of endogenous USP33. We also
      revealed that beta-TrCP interacted with USP33 independently of the classic
      binding motif for beta-TrCP, and mediated USP33 degradation via the ubiquitin
      proteasome pathway. Furthermore, we found that the WD40 motif of beta-TrCP and
      201-400 amino acid motif of USP33 are required for the interaction between beta
      TrCP and USP33. Consequently, beta-TrCP attenuated USP33-mediated inhibition of
      cell proliferation and cell invasion. Taken together, our study clarified that
      the E3 ligase beta-TrCP regulates cellular USP33 levels by the ubiquitin
      proteasomal proteolysis.

PMID- 28506876
TI  - Role of prostacyclin synthase in carcinogenesis.
AB  - Prostacyclin (PGI2) synthase (PGIS) and microsomal prostaglandin (PG) E synthase
      1 (PGES-1) functionally couple with inducible cyclooxygenase-2 (COX-2) as their
      upstream enzymes to produce PGI2 and PGE2, respectively. Non-steroidal anti
      inflammatory drugs exert their pharmacological effects including antitumor
      effects by the inhibition of COX-2 and thereby suppress this PG biosynthesis.
      PGIS is abundantly expressed in vascular endothelial and smooth muscle cells and
      was shown to be critical for the regulation of platelet aggregation and vascular
      tone. In addition to its role in vascular regulation, PGIS was shown to be
      frequently down-regulated in several types of cancers, and the involvement of
      PGIS in carcinogenesis has been suggested. In this review, we summarize the
      current understanding of the roles of PGIS and PGIS-derived PGI2 in
      carcinogenesis.

PMID- 28506877
TI  - Clinical Practice Guidelines: Synthesis of the guidelines for the surgical
      treatment of primary pelvic organ prolapse in women by the AFU, CNGOF, SIFUD-PP,
      SNFCP, and SCGP.

PMID- 28506878
TI  - Pain-motor integration in the primary motor cortex in Parkinson's disease.
AB  - BACKGROUND: In Parkinson's disease (PD), the influence of chronic pain on motor
      features has never been investigated. We have recently designed a technique that
      combines nociceptive system activation by laser stimuli and primary motor cortex
      (M1) activation through transcranial magnetic stimulation (TMS), in a laser
      paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces
      long-term changes in motor evoked potentials reflecting M1 long-term potentiation
      like plasticity, arising from pain-motor integration. OBJECTIVE: We here examined
      the possible influence of chronic pain on motor responses to Laser-PAS in
      patients with PD, with and without chronic pain. METHODS: We compared motor
      responses to Laser-PAS in healthy subjects and in patients with PD, with and
      without chronic pain. RESULTS: Unlike controls, we found reduced responses to
      Laser-PAS in patients with PD, with and without pain. Patients off and on
      dopaminergic therapy had similar responses to Laser-PAS. When comparing responses
      to Laser-PAS in patients with and without pain, the two patients' subgroups had
      similar abnormalities. When we compared patients with pain in the body region
      investigated with Laser-PAS, with those with pain in other body regions, we found
      prominent changes in patients with homotopic pain. Finally, when comparing Laser
      PAS with the original PAS protocol, which combines electric peripheral nerve
      stimuli and TMS, in patients without pain and those with homotopic pain, we found
      similar responses to both techniques in patients without pain, whereas Laser-PAS
      induced greater abnormalities than PAS in patients with pain. CONCLUSIONS: In PD,
      chronic pain degrades response to Laser-PAS through abnormal pain-motor
      integration.

PMID- 28506879
TI  - A new platform for long-term tracking and recording of neural activity and
      simultaneous optogenetic control in freely behaving Caenorhabditis elegans.
AB  - BACKGROUND: Real-time recording and manipulation of neural activity in freely
      behaving animals can greatly advance our understanding of how neural circuits
      regulate behavior. Ca2+ imaging and optogenetic manipulation with optical probes
      are key technologies for this purpose. However, integrating the two optical
      approaches with behavioral analysis has been technically challenging. NEW METHOD:
      Here, we developed a new imaging system, ICaST (Integrated platform for Ca2+
      imaging, Stimulation, and Tracking), which combines an automatic worm tracking
      system and a fast-scanning laser confocal microscope, to image neurons of
      interest in freely behaving C. elegans. We optimized different excitation
      wavelengths for the concurrent use of channelrhodopsin-2 and G-CaMP, a green
      fluorescent protein (GFP)-based, genetically encoded Ca2+ indicator. RESULTS:
      Using ICaST in conjunction with an improved G-CaMP7, we successfully achieved
      long-term tracking and Ca2+ imaging of the AVA backward command interneurons
      while tracking the head of a moving animal. We also performed all-optical
      manipulation and simultaneous recording of Ca2+ dynamics from GABAergic motor
      neurons in conjunction with behavior monitoring. COMPARISON WITH EXISTING
      METHOD(S): Our system differs from conventional systems in that it does not
      require fluorescent markers for tracking and can track any part of the worm's
      body via bright-field imaging at high magnification. Consequently, this approach
      enables the long-term imaging of activity from neurons or nerve processes of
      interest with high spatiotemporal resolution. CONCLUSION: Our imaging system is a
      powerful tool for studying the neural circuit mechanisms of C. elegans behavior
      and has potential for use in other small animals.

PMID- 28506881
TI  - Altered circadian patterns of salivary cortisol in individuals with
      schizophrenia: A critical literature review.
AB  - This article focuses on stress vulnerability in schizophrenia through an
      integrated clinical and biological approach. The objective of this article is to
      better understand the relationships between vulnerability, stress and
      schizophrenia. First, the concept of vulnerability is defined and several models
      of vulnerability in schizophrenia are reviewed. Second, a section is developed on
      the biology of stress, and more specifically on the stress responses of the
      hypothalamo-pitutary adrenal (HPA) axis. Then, studies of cortisol circadian
      rhythms are summarized, suggesting hyper-reactivity of the HPA axis in patients
      with schizophrenia and high risk individuals for schizophrenia. The results
      support the models of stress vulnerability in schizophrenia and the hypothesis of
      high cortisol levels as an endophenotype in this disorder. In conclusion, this
      article highlights the interest of studying the cortisol circadian rhythms in
      schizophrenia and opens the perspective to identify high risk individuals for
      schizophrenia by measuring circadian patterns of salivary cortisol.

PMID- 28506880
TI  - Advanced correlation grid: Analysis and visualisation of functional connectivity
      among multiple spike trains.
AB  - BACKGROUND: This study analyses multiple spike trains (MST) data, defines its
      functional connectivity and subsequently visualises an accurate diagram of
      connections. This is a challenging problem. For example, it is difficult to
      distinguish the common input and the direct functional connection of two spike
      trains. NEW METHOD: The new method presented in this paper is based on the
      traditional pairwise cross-correlation function (CCF) and a new combination of
      statistical techniques. First, the CCF is used to create the Advanced Correlation
      Grid (ACG) correlation where both the significant peak of the CCF and the
      corresponding time delay are used for detailed analysis of connectivity. Second,
      these two features of functional connectivity are used to classify connections.
      Finally, the visualization technique is used to represent the topology of
      functional connections. RESULTS: Examples are presented in the paper to
      demonstrate the new Advanced Correlation Grid method and to show how it enables
      discrimination between (i) influence from one spike train to another through an
      intermediate spike train and (ii) influence from one common spike train to
      another pair of analysed spike trains. COMPARISON WITH EXISTING METHODS: The ACG
      method enables scientists to automatically distinguish between direct connections
      from spurious connections such as common source connection and indirect
      connection whereas existing methods require in-depth analysis to identify such
      connections. CONCLUSIONS: The ACG is a new and effective method for studying
      functional connectivity of multiple spike trains. This method can identify
      accurately all the direct connections and can distinguish common source and
      indirect connections automatically.

PMID- 28506882
TI  - Examination of the superoxide/hydrogen peroxide forming and quenching potential
      of mouse liver mitochondria.
AB  - Pyruvate dehydrogenase (PDHC) and alpha-ketoglutarate dehydrogenase complex
      (KGDHC) are important sources of reactive oxygen species (ROS). In addition, it
      has been found that mitochondria can also serve as sinks for cellular hydrogen
      peroxide (H2O2). However, the ROS forming and quenching capacity of liver
      mitochondria has never been thoroughly examined. Here, we show that mouse liver
      mitochondria use catalase, glutathione (GSH), and peroxiredoxin (PRX) systems to
      quench ROS. Incubation of mitochondria with catalase inhibitor 3-amino-1,2,4
      triazole (triazole) induced a significant increase in pyruvate or alpha
      ketoglutarate driven O2-/H2O2 formation. 1-Choro-2,4-dinitrobenzene (CDNB), which
      depletes glutathione (GSH), elicited a similar effect. Auranofin (AF), a
      thioredoxin reductase-2 (TR2) inhibitor which disables the PRX system, did not
      significantly change O2-/H2O2 formation. By contrast catalase, GSH, and PRX were
      all required to scavenging extramitochondrial H2O2. In this study, the ROS
      forming potential of PDHC, KGDHC, Complex I, and Complex III was also profiled.
      Titration of mitochondria with 3-methyl-2-oxovaleric acid (KMV), a specific
      inhibitor for O2-/H2O2 production by KGDHC, induced a ~86% and ~84% decrease in
      ROS production during alpha-ketoglutarate and pyruvate oxidation. Titration of
      myxothiazol, a Complex III inhibitor, decreased O2-/H2O2 formation by ~45%.
      Rotenone also lowered ROS production in mitochondria metabolizing pyruvate or
      alpha-ketoglutarate indicating that Complex I does not contribute to ROS
      production during forward electron transfer from NADH. Taken together, our
      results indicate that KGDHC and Complex III are high capacity sites for O2-/H2O2
      production in mouse liver mitochondria. We also confirm that catalase plays a
      role in quenching either exogenous or intramitochondrial H2O2.

PMID- 28506883
TI  - Effects of cardiotonic steroids on isolated perfused kidney and NHE3 activity in
      renal proximal tubules.
AB  - Cardiotonic steroids (CS) are known as modulators of sodium and water
      homeostasis. These compounds contribute to the excretion of sodium under overload
      conditions due to its natriuretic property related to the inhibition of the renal
      Na+/K+-ATPase (NKA) pump alpha1 isoform. NHE3, the main route for Na+
      reabsorption in the proximal tubule, depends on the Na+ gradient generated by the
      NKA pump. In the present study we aimed to investigate the effects of
      marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated
      perfused rat kidney and on the inhibition of NKA activity. Furthermore, we
      investigated the mechanisms for the cardiotonic steroid-mediated natriuretic
      effect, by evaluating and comparing the effects of bufalin (BUF), ouabain (OUA),
      MBG and TBG on NHE3 activity in the renal proximal tubule in vivo. TBG
      significantly increased GFR, UF, natriuresis and kaliuresis in isolated perfused
      rat kidney, and inhibits the activity of NKA at a much higher rate than MBG. By
      stationary microperfusion technique, the perfusion with BUF, OUA, TBG or MBG
      promoted an inhibitory effect on NHE3 activity, whereas BUF was the most
      effective agent, and demonstrated a dose-dependent response, with maximal
      inhibition at 50nM. Furthermore, our data showed the role of NKA-Src kinase
      pathway in the inhibition of NHE3 by CS. Finally, a downstream step, MEK1/2
      ERK1/2 was also investigated, and, similar to Src inhibition, the MEK1/2
      inhibitor (U0126) suppressed the BUF effect. Our findings indicate the
      involvement of NKA-SRc-Kinase-Ras-Raf-ERK1/2 pathway in the downregulation of
      NHE3 by cardiotonic steroids in the renal proximal tubule, promoting a reduction
      of proximal sodium reabsorption and natriuresis.

PMID- 28506884
TI  - Enhancing effect of 50 Hz rotating magnetic field on induction of Shiga toxin
      converting lambdoid prophages.
AB  - Studies aimed at investigating factors and mechanism of induction of prophages, a
      major pathogenesis factor of Shiga toxin-producing Escherichia coli (STEC), are
      considered important to develop an effective treatment for STEC infections. In
      this study, we demonstrated the synergistic effect of the rotating magnetic field
      (RMF) of induction B = 34 mT and frequency f = 50 Hz at a constant temperature of
      37  degrees C and mitomycin C (MMC), that resulted in a higher level of induction
      of stx-carrying lambdoid Stx prophages. This is a first report on the induction
      of lambdoid Stx prophages in response to the enhancing effect of popular inductor
      (mitomycin C) under the influence of RMF.

PMID- 28506885
TI  - High proportions of Staphylococcus epidermidis in dental caries harbor multiple
      classes of antibiotics resistance, significantly increase inflammatory
      interleukins in dental pulps.
AB  - Staphylococcus epidermidis is one of most prevalent in dental caries or dental
      pulp which has the capability of horizontal genetic transfer between different
      bacterial species in the oropharynx, suggesting that it may evolve with the
      dissemination of resistant determinants, This study was performed to molecularly
      characterize and differentiate S. epidermidis isolated from dental caries and
      healthy individual. Also, two important cytokines in inflammation were assayed
      caused due to S. epidermidis of health and dental caries sources. Dental caries
      strains were more resistant with high MIC 50 and MIC 90 value. These isolates
      also showed the presence of mecA gene and another virulence gene i. e sea and seb
      comparatively more than healthy individual isolates. SCCmec types, III and IV was
      more prevalent in dental caries isolates where an as healthy individual was more
      non-typable. Additionally, the quantity of IL-1beta and IL-8 caused due to dental
      caries isolates was seen more which indicate dental caries isolates are able to
      induce. This study showed that S. epidermidis a normal flora of oropharyngeal are
      more diverse to those strains which cause dental caries. S. epidermidis owns a
      prodigious genetic plasticity that permits to obtain, lose or regulate genetic
      elements that provide compensations to improve its colonization in the host.

PMID- 28506887
TI  - Molecular investigation of virulence factors of Brucella melitensis and Brucella
      abortus strains isolated from clinical and non-clinical samples.
AB  - Brucella is zoonotic pathogen that induces abortion and sterility in domestic
      mammals and chronic infections in humans called Malta fever. It is a facultative
      intracellular potential pathogen with high infectivity. The virulence of Brucella
      is dependent upon its potential virulence factors such as enzymes and cell
      envelope associated virulence genes. The aim of this study was to investigate the
      Brucella virulence factors among strains isolated from humans and animals in
      different parts of Iran. Seventy eight strains of Brucella species isolated from
      suspected human and animal cases from several provinces of Iran during 2015-2016
      and identified by phenotypic and molecular methods. The multiplex-PCR (M-PCR)
      assay was performed in order to detect the ure, wbkA, omp19, mviN, manA and perA
      genes by using gene specific primers. Out of 78 isolates of Brucella spp., 57
      (73%) and 21 (27%) isolates were detected as B. melitensis and B. abortus,
      respectively, by molecular method. The relative frequency of virulence genes ure,
      wbkA, omp19, mviN, manA and perA were 74.4%, 89.7%, 93.6%, 94.9%, 100% and 92.3%,
      respectively. Our results indicate that the most of Brucella strains isolated
      from this region possess high percent of virulence factor genes (ure, wbkA,
      omp19, mviN, manA and perA) in their genome. So, each step of infection can be
      mediated by a number of virulence factors and each strain may have a unique
      combination of these factors that affected the rate of bacterial pathogenesis.

PMID- 28506886
TI  - Experimental mouse lethality of Escherichia coli strains isolated from free
      ranging Tibetan yaks.
AB  - The present study has examined the virulence potential of Escherichia coli
      isolates harboring at least one virulence gene (associated with ExPEC or InPEC
      pathotype and belonging to different phylogenetic groups: A, B1, B2 or D),
      isolated from free ranging Tibetan yak feces. The E. coli isolates (n = 87) were
      characterized for different serogroups and a mouse model of subcutaneous
      infection was used to envisage the virulence within these E. coli strains. Of the
      87 E. coli isolates examined, 23% of the E. coli isolates caused lethal
      infections in a mouse model of subcutaneous infection and were classified as
      killer. Moreover, the majority of the killer strains belonged to phylogroup A
      (65%) and serogroup O60 or O101 (35%). Phylogroup B1, serogroups O60 and O101
      were statistically associated with the killer status (P < 0.05). However,
      positive associations (OR >1) were observed between the killer status isolates
      and all other bacterial virulence traits. This study comprises the first report
      on the virulence potential of E. coli strains isolated from free-ranging Tibetan
      yaks feces. Our findings suggest that pathogenic E. coli of free ranging yaks is
      highly worrisome, as these feces are used as manures by farmers and therewith
      pose a health risk to humans upon exposure.

PMID- 28506888
TI  - Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of
      human dental pulp cells.
AB  - Activation of the G protein-coupled calcium-sensing receptor (CaSR) has crucial
      roles in skeletal development and bone turnover. Our recent study has identified
      a role for activated CaSR in the osteogenic differentiation of human periodontal
      ligament stem cells. Furthermore, odontoblasts residing inside the tooth pulp
      chamber play a central role in dentin formation. However, it remains unclear how
      CaSR activation affects the odontoblastic differentiation of human dental pulp
      cells (HDPCs). We have investigated the odontoblastic differentiation of HDPCs
      exposed to elevated levels of extracellular calcium (Ca) and strontium (Sr), and
      the contribution of CaSR and the L-type voltage-dependent calcium channel (L
      VDCC) to this process. Immunochemical staining of rat dental pulp tissue
      demonstrated that CaSR was expressed at high levels in the odontoblastic layer,
      moderate levels in the sublayer, and low levels in the central pulp tissue.
      Although normal HDPCs expressed low levels of CaSR, stimulation with Ca or Sr
      promoted both CaSR expression and odontoblastic differentiation of HDPCs along
      with increased expression of odontoblastic makers. These effects were inhibited
      by treatment with a CaSR antagonist, whereas treatment with an L-VDCC inhibitor
      had no effect. Additionally, knockdown of CaSR with siRNA suppressed
      odontoblastic differentiation of Ca- and Sr-treated HDPCs. ERK1/2 phosphorylation
      was observed in Ca- and Sr-treated HDPCs, whereas CaSR antagonist treatment or
      CaSR knockdown blocked ERK1/2 phosphorylation. Furthermore, inhibition of ERK1/2
      suppressed mineralization of Ca- and Sr-treated HDPCs. These results suggest that
      elevated concentrations of extracellular Ca and Sr induce odontoblastic
      differentiation of HDPCs through CaSR activation and the ERK1/2 phosphorylation.

PMID- 28506890
TI  - Biomechanics of the transport barrier in the nuclear pore complex.
AB  - The nuclear pore complex (NPC) is the selective gateway through which all
      molecules must pass when entering or exiting the nucleus. It is a cog in the gene
      expression pathway, an entrance to the nucleus exploited by viruses, and a highly
      tuned nanoscale filter. The NPC is a large proteinaceous assembly with a central
      lumen occluded by natively disordered proteins, known as FG-nucleoporins (or FG
      nups). These FG-nups, along with a family of soluble proteins known as nuclear
      transport receptors (NTRs), form the selective transport barrier. Although much
      is known about the transport cycle and the necessity of NTRs for chaperoning
      cargo molecules through the NPC, the mechanism by which NTRs and NTR*cargo
      complexes translocate the selective transport barrier is not well understood. How
      can disordered FG-nups and soluble NTRs form a transport barrier that is
      selective, ATP-free, and fast? In this work, we review various mechanical
      approaches - both experimental and theoretical/computational - employed to better
      understand the morphology of the FG-nups, and their role in nucleocytoplasmic
      transport. Recent experiments on FG-nups tethered to planar surfaces, coupled
      with quantitative modelling work suggests that FG-nup morphologies are the result
      of a finely balanced system with significant contributions from FG-nup
      cohesiveness and entropic repulsion, and from NTR*FG-nup binding avidity; whilst
      AFM experiments on intact NPCs suggest that the FG-nups are sufficiently cohesive
      to form condensates in the centre of the NPC lumen, which may transiently
      dissolve to facilitate the transport of larger cargoes.

PMID- 28506889
TI  - NFAM1 signaling enhances osteoclast formation and bone resorption activity in
      Paget's disease of bone.
AB  - Paget's disease of bone (PDB) is marked by the focal activity of abnormal
      osteoclasts (OCLs) with excess bone resorption. We previously detected measles
      virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB.
      Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the
      mechanism by which MVNP induces excess OCLs/bone resorption activity in PDB is
      unclear. Microarray analysis identified MVNP induction of NFAM1 (NFAT activating
      protein with ITAM motif 1) expression. Therefore, we hypothesize that MVNP
      induction of NFAM1 enhances OCL differentiation and bone resorption in PDB. MVNP
      transduced normal human PBMC showed an increased NFAM1 mRNA expression without
      RANKL treatment. Further, bone marrow cells from patients with PDB demonstrated
      elevated levels of NFAM1 mRNA expression. Interestingly, shRNA suppression of
      NFAM1 inhibits MVNP induced OCL differentiation and bone resorption activity in
      mouse bone marrow cultures. Live cell widefield fluorescence microscopy analysis
      revealed that MVNP induced intracellular Ca2+ oscillations and levels were
      significantly reduced in NFAM1 suppressed preosteoclasts. Further, western blot
      analysis demonstrates that shRNA against NFAM1 inhibits MVNP stimulated PLCgamma,
      calcineurin, and Syk activation in preosteoclast cells. Furthermore, NFAM1
      expression controls NFATc1, a critical transcription factor expression and
      nuclear translocation in MVNP transuded preosteoclast cells. Thus, our results
      suggest that MVNP modulation of the NFAM1 signaling axis plays an essential role
      in pagetic OCL formation and bone resorption activity.

PMID- 28506891
TI  - Viral mechanisms for docking and delivering at nuclear pore complexes.
AB  - Some viruses possess the remarkable ability to transport their genomes across
      nuclear pore complexes (NPCs) for replication inside the host cell's intact
      nuclear compartment. Viral mechanisms for crossing the restrictive NPC passageway
      are highly complex and astonishingly diverse, requiring in each case stepwise
      interaction between incoming virus particles and components of the nuclear
      transport machinery. Exactly how a large viral genome loaded with accessory
      proteins is able to pass through the relatively narrow central channel of the NPC
      without causing catastrophic structural damage is not yet fully understood. It
      appears likely, however, that the overall structure of the NPC changes in
      response to the cargo. Translocation may result in nucleic acids being
      misdelivered to the cytoplasm. Here we consider in detail the diverse strategies
      that viruses have evolved to target and subvert NPCs during infection. For
      decades, this process has both captivated and confounded researchers in the
      fields of virology, cell biology, and structural biology.

PMID- 28506893
TI  - MACPF/CDC proteins in development: Insights from Drosophila torso-like.
AB  - The Membrane Attack Complex Perforin-like/Cholesterol-Dependent Cytolysin (MACPF)
      superfamily is an ancient and biologically diverse group of proteins that are
      best known for pore-forming roles in mammalian immunity and bacterial
      pathogenesis. Intriguingly, however, some eukaryotic proteins which contain the
      MACPF domain that defines this family do not act in attack or defence, and
      instead have distinct developmental functions. It remains unclear whether these
      proteins function via pore formation or have a different mechanism of action. Of
      these, by far the best characterised is Torso-like (Tsl), the only MACPF member
      that has been identified in the fruit fly, Drosophila melanogaster. While it has
      long been known to have a role in embryonic patterning, recent studies have shown
      that Tsl in fact has multiple roles in development. As such, it presents an
      excellent opportunity to investigate how the MACPF domain functions in a
      developmental context. Here, we review what is known about Tsl in Drosophila and
      other insects, and discuss the potential molecular mechanism by which Tsl and
      thus other developmental MACPF proteins may function.

PMID- 28506894
TI  - The functional versatility of the nuclear pore complex proteins.
AB  - Over the past few decades, it is increasingly evident that nucleoporins are multi
      functional proteins that are not only pivotal for the formation of the nuclear
      pore complex. They also have key roles in mitosis, gene expression, development
      and disease. In this review, the versatility and functions of nucleoporins
      outside the NPC will be discussed.

PMID- 28506895
TI  - The Node and beyond-using social media in cell and developmental biology.
AB  - Traditionally, strong scientific communities have been at least partly built
      around physical proximity - either by members of the same department or
      institute, or through regular meetings and conferences. The online environment
      and the rise of social media platforms now make it easier to build virtual
      communities of geographically dispersed people with a common interest. In this
      article, we explore how such networks can be nurtured, focussing on the Node - a
      community blog for and by developmental biologists. We also discuss the value of
      social media outlets like Twitter in building and maintaining scientific
      communities online.

PMID- 28506892
TI  - The roles of the nuclear pore complex in cellular dysfunction, aging and disease.
AB  - The study of the Nuclear Pore Complex (NPC), the proteins that compose it
      (nucleoporins), and the nucleocytoplasmic transport that it controls have
      revealed an unexpected layer to pathogenic disease onset and progression. Recent
      advances in the study of the regulation of NPC composition and function suggest
      that the precise control of this structure is necessary to prevent diseases from
      arising or progressing. Here we discuss the role of nucleoporins in a diverse set
      of diseases, many of which directly or indirectly increase in occurrence and
      severity as we age, and often shorten the human lifespan. NPC biology has been
      shown to play a direct role in these diseases and therefore in the process of
      healthy aging.

PMID- 28506896
TI  - Neurodevelopmental MACPFs: The vertebrate astrotactins and BRINPs.
AB  - Astrotactins (ASTNs) and Bone morphogenetic protein/retinoic acid inducible
      neural-specific proteins (BRINPs) are two groups of Membrane Attack
      Complex/Perforin (MACPF) superfamily proteins that show overlapping expression in
      the developing and mature vertebrate nervous system. ASTN(1-2) and BRINP(1-3)
      genes are found at conserved loci in humans that have been implicated in
      neurodevelopmental disorders (NDDs). Here we review the tissue distribution and
      cellular localization of these proteins, and discuss recent studies that provide
      insight into their structure and interactions. We highlight the genetic
      relationships and co-expression of Brinps and Astns; and review recent knock-out
      mouse phenotypes that indicate a possible overlap in protein function between
      ASTNs and BRINPs.

PMID- 28506897
TI  - Aegerolysins: Lipid-binding proteins with versatile functions.
AB  - Proteins of the aegerolysin family span many kingdoms of life. They are
      relatively widely distributed in bacteria and fungi, but also appear in plants,
      protozoa and insects. Despite being produced in abundance in cells at specific
      developmental stages and present in secretomes, only a few aegerolysins have been
      studied in detail. In particular, their organism-specific physiological roles are
      intriguing. Here, we review published findings to date on the distribution,
      molecular interactions and biological activities of this family of structurally
      and functionally versatile proteins, the aegerolysins.

PMID- 28506898
TI  - Chromane isolated from leaves of Dillenia indica improves the neuronal
      dysfunction in STZ-induced diabetic neuropathy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: According to the Indian traditional medicine,
      Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and
      leaves of the plant possess anti-oxidant and anti-inflammatory properties.
      Reactive oxygen species, formation of advanced glycation end products (AGEs) and
      apoptosis are implicated in the pathogenesis of diabetic neuropathy. AIM OF THE
      STUDY: The aim of the present study was to explore the effect of D. indica and
      its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia,
      MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental
      diabetes. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal
      administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic
      neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5
      and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ
      administration. Development of neuropathy was evident from a marked hyperalgesia
      and allodynia; reduced MNCV associated with increased formation of AGEs and
      reactive oxygen species. RESULTS: significantly attenuated behavioral and
      biochemical changes associated with diabetic neuropathy. Present study suggested
      that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via
      modulation of oxidative-nitrosative stress and reduction in AGEs formation in the
      diabetic rats. CONCLUSION: Thus D. indica might be beneficial in chronic
      diabetics, ameliorate the progression of diabetic neuropathy and may also find
      application in diabetic neuropathic pain.

PMID- 28506899
TI  - Hepatoprotective activities of Antrodia camphorata and its triterpenoid compounds
      against CCl4-induced liver injury in mice.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Antrodia camphorata (AC) is a rare and precious
      fungus indigenous to Taiwan used as a traditional medicine for the treatment of
      liver injury. Triterpenoids are the major bioactive constituents of A. camphorata
      and have been reported to possess hepatoprotective activities. To meet the
      increasing demand, artificial cultivation techniques have been developed. AIM OF
      THE STUDY: This study aims to evaluate the hepatoprotective activities of AC
      samples derived from different cultivation techniques and to dissect the main
      active triterpenoid compounds. MATERIALS AND METHODS: The ethanol extracts of
      five batches of AC samples, including wild growing fruiting bodies, cutting wood
      culture fruiting bodies, dish cultures, cutting wood culture mycelia, and
      submerged fermentation mycelia were orally administered (50mg/kg or 200mg/kg) to
      ICR mice for 7 days. On the last day, CCl4 (0.2%, 7mL/kg, i.p.) was used to
      induce liver injury, and the activities of serum alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) were determined 24h after the injection.
      Moreover, a HepG2 cell model treated with CCl4 (0.35%) was used to screen the
      protective activities of 29 AC triterpenoids. After incubation for 6h,
      viabilities of the cells were tested using MTS assay. The in vivo
      hepatoprotective activities of antcin B and antcin K were further studied on the
      mice model by ALT and AST tests and histopathologic examinations. To elucidate
      the mechanisms, the mRNA levels of iNOS, COX2, TNF-alpha and IL-1beta, and the
      protein levels of NF-kappaB (p65/p-p65), iNOS and COX2 in liver tissues were
      determined. RESULTS: The wild growing or cutting wood culture fruiting bodies,
      and the dish cultures of AC showed more potent activities than the mycelia
      (P<0.001). At 20MUM, 16 of 29 triterpenoids showed significant protective
      activities, increasing HepG2 cell viability from 46% of the CCl4 group to >90%.
      Antcin B and antcin K could dose-dependently (10 or 50mg/kg, 7 days, i.g.)
      decrease the serum levels of ALT and AST, and decrease the incidence of liver
      necrosis. The effects of 50mg/kg of antcin K or antcin B were almost identical to
      those of 100mg/kg silymarin. Furthermore, qRT-PCR and Western blotting analyses
      revealed they could down-regulate IL-1beta, TNF-alpha, iNOS, COX-2 and NF-kappaB
      in liver tissues at both transcriptional and translational levels. CONCLUSION:
      The results indicate that cultivation techniques remarkably affect the
      hepatoprotective activities of AC. Antcin K and antcin B are the major
      hepatoprotective compounds of A. camphorata, and the mechanism is related with
      anti-inflammation. Given its high natural abundance and good oral absorption,
      antcin K could be a promising drug candidate for liver injury.

PMID- 28506900
TI  - Chinese materia medica used in medicinal diets.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal diets have a history of more than 2000
      years. Locally referred to as yaoshan (Chinese: ), a medicinal diet is understood
      in China as a dietary product that combines herbs and food with the purpose of
      preventing and treating diseases or improving health under the guidance of
      traditional Chinese medicine theory. Medicinal diets are used in Chinese people's
      daily life and in specialized restaurants. Hundreds of Chinese materia medica
      (CMM) are used in medicinal diets; however, a comprehensive evaluation of
      medicinal diets is lacking. AIMS OF THE STUDY: This is an exploratory study that
      aims to identify the CMM that are most frequently used in medicinal diets and to
      provide an updated view of the current situation of medicinal diets in China.
      MATERIALS AND METHODS: A field study of 1221 people in 32 Chinese provinces was
      conducted over a period of approximately 6 months and included various types of
      interviews as well as a written questionnaire. Two approaches were used to
      analyse the data collected in the survey: (1) estimating the frequency of CMM
      consumed in daily diets; and (2) collecting CMM used in medicinal diet
      restaurants. Complementary information on the selected CMM was obtained from
      relevant databases, including PubMed, Google Scholar, Baidu Scholar, CNKI, and
      Web of Science. RESULTS: Ten CMM were reported as commonly used by more than 50%
      of the participants. Among these 10 species, most medicinally used parts were
      seeds and fruits. Pharmacological data from the literature revealed that these
      species are associated with a wide spectrum of biological properties, including
      antitumour (80%), antioxidant (50%), anti-diabetic (40%), antilipemic (40%), anti
      aging (40%), antimicrobial (40%) and cardioprotective (40%) activities. Our
      survey shows that most medicinal diet restaurants are located in the eastern part
      of China, with the greatest numbers being found in Beijing and Guangzhou. Only
      Dioscoreae Rhizoma, Lycii Fructus, Chrysanthemi Flos and Longan Arillus were
      frequently consumed both in daily diets and at medicinal diet restaurants. Some
      of the similarities shared by these 4 species include an extensive history of use
      (>2000 years); a sweet flavour; and antioxidant, antidiabetic, antilipemic and
      cardioprotective effects. CONCLUSIONS: The 10 most commonly consumed CMM possess
      various biological effects that are currently target the most frequent health
      problems for the majority of the population. The development of medicinal diet
      restaurants has certain regional restrictions and is associated with the local
      climate environment and dietary culture. The data revealed by this study provided
      useful information for commercial exploitation of medicinal diets and their
      components and serve as a basis for further studies on various aspects of
      medicinal diets.

PMID- 28506901
TI  - New Isoflavonoids from the extract of Rhynchosia precatoria (Humb. & Bonpl. ex
      Willd.) DC. and their antimycobacterial activity.
AB  - ETHNOPHARMACOLOGY RELEVANCE: The evaluation of the antimycobacterial activity of
      extracts of medicinal plants used by Mayos against tuberculosis and respiratory
      problems, allowed the identification of Rhynchosia precatoria (Humb. & Bonpl. ex
      Willd.) DC (Fabaceae) as the best candidate to find new antimycobacterial
      compounds. AIM OF THE STUDY: To isolate and characterize the compounds of R.
      precatoria responsible for the inhibitory and bactericidal activity against
      Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis ATCC 700084. To
      determine antimycobacterial synergistic effect of pure compounds and their
      selectivity index towards Vero cells. MATERIALS AND METHODS: A total of six
      flavonoids were purified by silica gel column chromatography. Structural
      elucidation of the isolated compounds was achieved by using 1D and 2D NMR
      spectroscopy techniques. The configuration at the C-3 chiral center was
      established by quantum mechanical calculation of the electronic circular
      dichroism (ECD) spectrum. In vitro inhibitory and bactericidal activity against
      M. tuberculosis and M. smegmatis were determined with the redox indicator Alamar
      Blue (resazurin). Synergy was determined by X/Y quotient. Cytotoxicity was
      measured by MTT assay. RESULTS: The isolated compounds were identified as
      precatorin A (1), precatorin B (2), precatorin C (3), lupinifolin (4), cajanone
      (5) and lupinifolinol (6). Compounds 1-3 are new. Compounds 1 to 5 inhibited the
      growth of M. tuberculosis (MIC >=31.25ug/mL); compounds 1, 2, 4 and 5 killed the
      bacteria (MBC >=31.25ug/mL) and also inhibited M. smegmatis (MIC >=125ug/mL),
      while 1 and 4 also resulted bactericidal (MBC >=125ug/mL). Compounds 4 and 5
      presented synergistic effect (X/Y quotient value <0.5) at a concentration of 1/2
      MIC of each compound in the combination. Cytotoxicity in murine macrophages (RAW
      264.7 cells) gave IC50 values of 13.3-46.98uM, for compounds 1-5. CONCLUSIONS: In
      this work we isolated two new isoflavanones (1 and 2), and one new isoflavone (3)
      with a weak antimycobacterial activity. The (3R) absolute configuration was
      assigned to 1 by computational analysis of its ECD spectrum and to 2 and 5 by
      similarity of their ECD spectra with that of 1. We are also reporting by first
      time, activity against virulent strain of M. tuberculosis for compounds 4 and 5
      and their antimycobacterial synergistic effect.

PMID- 28506902
TI  - SKI3301, a purified herbal extract from Sophora tonkinensis, inhibited airway
      inflammation and bronchospasm in allergic asthma animal models in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sophora tonkinensis (Leguminosae, ST) is a
      traditional herbal plant in Korea and China. Its roots and rhizomes have been
      used to dissipate heat, to clear toxic material and to treat acute
      pharyngolaryngeal infections and sore throats. AIM OF STUDY: In this study, we
      tried to investigate the anti-inflammatory and anti-asthmatic effects of a
      purified extract (SKI3301) from Sophora tonkinensis using in vitro enzyme assay
      models and ovalbumin (OVA)-induced asthma animal models. MATERIALS AND METHODS:
      The effect of SKI3301 on pro-inflammatory enzymes such as 5-lipoxygenase,
      phosphodiesterase 3 & 4, and thromboxane synthase was assayed in vitro. BALB/c
      mice were sensitized with OVA/Alum ip injection and nebulized with OVA to induce
      airway inflammation. Bronchoalveolar lavage (BAL) fluid was collected and
      analyzed for leukocytes infiltration and IL-5 production along with lung
      histopathology. Guinea pigs passively sensitized with anti-OVA antiserum were
      used to investigate the effect of SKI3301 on bronchospasm in vitro and in vivo.
      RESULTS: SKI3301 potently inhibited the activities of 5-lipoxygenase,
      phosphodiesterase 3 & 4, and thromboxane synthase. Orally administered SKI3301
      attenuated the total leukocytes and eosinophil infiltration and IL-5 level in BAL
      fluids. Histopathological changes associated with lung inflammation were also
      reduced by SKI3301. SKI3301 inhibited OVA-induced contraction of isolated trachea
      from sensitized guinea pigs. SKI3301 also protected OVA-induced
      bronchoconstriction in the sensitized guinea pigs. Maackiain, one of 3 major
      components of SKI3301, was effective in inhibiting 5-lipoxygenase and OVA-induced
      airway inflammation. CONCLUSION: In this study, SKI3301 potently inhibited pro
      inflammatory enzymes and attenuated OVA-induced bronchospasm in animal model of
      allergic asthma. These results suggest that SKI3301 may have therapeutic
      potential for allergic asthma.

PMID- 28506903
TI  - Ethnozoological assessment of animals used by Mon traditional medicine vendors at
      Kyaiktiyo, Myanmar.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Wild animals are widely used in traditional Asian
      medicine but information from Myanmar is lacking. We show that a wide range of
      animals are used at a pilgrimage site, mostly for their rendered fats and oils to
      be used in mixed concoctions. The majority of species were sold to be used to
      treat aching joints, muscle ache and skin diseases. AIM OF THE STUDY: To assess
      wildlife for sale for medicinal purposes, and document their medicinal use at
      Kyaiktiyo, a pilgrimage site at a 1100m tall mountain, with many of the pilgrims
      climbing to the top. In addition we address legal issues relating to the
      production and sale of traditional medicine that contain legally protected
      animals. MATERIAL AND METHODS: Four visits were made to Kyaiktiyo, Myanmar,
      between 2000 and 2017 to quantify animal parts on display and through discussions
      with vendors to obtain information on medicinal use of these parts. RESULTS:
      Twenty-three species, mostly mammals, were recorded to be used for traditional
      medicine. The most common were Chinese serow Capricornis milneedwardsii, Asian
      elephant Elephas maximus, and Asiatic black bear Ursus thibetanus. Over 600
      bodies or body parts were present. Combined, these parts purportedly provided
      cures or relief for at least 15 ailments or diseases. The most commonly mentioned
      treatment was that of using rendered animal fats/oils externally to relieve/cure
      aching joints or muscles. This treatment allegedly provides instant relief to
      pilgrims after an arduous climb up the mountain. Purported cures for various skin
      diseases was the next common use for the animal species on offer. Ten of the
      species observed for sale at Kyaiktiyo are listed as globally threatened, and 15
      are protected and cannot be legally traded. Ambiguities in Myanmar's legislation
      mean that protected animals or their body parts cannot be traded, however
      traditional medicines can be made out of them provided rules relating to the
      manufacturing of traditional medicines are adhered to. CONCLUSION: This study
      indicated that animals and their parts continue to be openly offered for sale at
      Kyaiktiyo to treat various illnesses. Despite these products potential medical,
      traditional or cultural importance, solutions have to been found on how to ensure
      that, in line with Myanmar's laws, use of traditional local medicine does not
      impede the conservation of imperilled species.

PMID- 28506904
TI  - Ordinal convolutional neural networks for predicting RDoC positive valence
      psychiatric symptom severity scores.
AB  - BACKGROUND: The CEGS N-GRID 2016 Shared Task in Clinical Natural Language
      Processing (NLP) provided a set of 1000 neuropsychiatric notes to participants as
      part of a competition to predict psychiatric symptom severity scores. This paper
      summarizes our methods, results, and experiences based on our participation in
      the second track of the shared task. OBJECTIVE: Classical methods of text
      classification usually fall into one of three problem types: binary, multi-class,
      and multi-label classification. In this effort, we study ordinal regression
      problems with text data where misclassifications are penalized differently based
      on how far apart the ground truth and model predictions are on the ordinal scale.
      Specifically, we present our entries (methods and results) in the N-GRID shared
      task in predicting research domain criteria (RDoC) positive valence ordinal
      symptom severity scores (absent, mild, moderate, and severe) from psychiatric
      notes. METHODS: We propose a novel convolutional neural network (CNN) model
      designed to handle ordinal regression tasks on psychiatric notes. Broadly
      speaking, our model combines an ordinal loss function, a CNN, and conventional
      feature engineering (wide features) into a single model which is learned end-to
      end. Given interpretability is an important concern with nonlinear models, we
      apply a recent approach called locally interpretable model-agnostic explanation
      (LIME) to identify important words that lead to instance specific predictions.
      RESULTS: Our best model entered into the shared task placed third among 24 teams
      and scored a macro mean absolute error (MMAE) based normalized score (100.(1
      MMAE)) of 83.86. Since the competition, we improved our score (using basic
      ensembling) to 85.55, comparable with the winning shared task entry. Applying
      LIME to model predictions, we demonstrate the feasibility of instance specific
      prediction interpretation by identifying words that led to a particular decision.
      CONCLUSION: In this paper, we present a method that successfully uses wide
      features and an ordinal loss function applied to convolutional neural networks
      for ordinal text classification specifically in predicting psychiatric symptom
      severity scores. Our approach leads to excellent performance on the N-GRID shared
      task and is also amenable to interpretability using existing model-agnostic
      approaches.

PMID- 28506906
TI  - Controlling liver cancer mortality on a global scale: Still a long way to go.

PMID- 28506905
TI  - Eight millimetre covered TIPS does not compromise shunt function but reduces
      hepatic encephalopathy in preventing variceal rebleeding.
AB  - BACKGROUND & AIMS: Currently, there are no recommendations in guidelines
      concerning the preferred diameter of stents for transjugular intrahepatic
      portosystemic shunt (TIPS), owing to the lack of adequate evidence. We therefore
      compared 8mm stents with 10mm stents, to evaluate whether 8mm stents would
      achieve similar shunt function, with less hepatic encephalopathy (HE) and better
      liver function. METHODS: Cirrhotic patients were randomly assigned to receive
      TIPS with an 8mm or 10mm covered stent to prevent variceal rebleeding. The
      primary endpoint was shunt dysfunction. All-cause rebleeding, orthotopic liver
      transplantation (OLT)-free survival, their composite endpoint, overt HE (overall
      and spontaneous) and liver function were designated as the secondary endpoints.
      RESULTS: From July 2012 to January 2014, 64 and 63 patients were allocated to the
      8mm and 10mm groups, respectively. During a median follow-up of 27months in both
      arms, dysfunction rates (16% vs. 16% at two years, p=0.62), two-year rebleeding
      (16% vs. 17%, p=0.65), OLT-free survival (95% vs. 86%, p=0.37), and the composite
      endpoint (p=0.62) were not statistically different between the groups. Despite a
      marginal decrease in overall overt HE, there were significantly fewer spontaneous
      overt HE incidents in the 8mm group within two years (27% vs. 43%, p=0.03), with
      a risk reduction of 47%. Notably, patients receiving 8mm stents also developed
      less hepatic impairment. CONCLUSIONS: TIPS with 8mm covered stents showed similar
      shunt function to TIPS with 10mm stents, but halved the risk of spontaneous overt
      HE and reduced hepatic impairment. Therefore, 8mm TIPS stents should be preferred
      for the prevention of variceal rebleeding in cirrhotic patients. Lay summary: The
      optimal diameter for transjugular intrahepatic portosystemic shunt (TIPS)
      remained uncertain. This study showed that TIPS with 8mm covered stents did not
      compromise shunt patency, or influence the efficacy of variceal rebleeding
      prevention compared to TIPS with 10mm stents, but reduced the risk of spontaneous
      overt hepatic encephalopathy and the incidence of severe encephalopathy.
      Moreover, liver function reserve was also better in the 8mm stents group,
      suggesting that 8mm TIPS stents should be preferred for the prevention of
      variceal rebleeding in cirrhotic patients.

PMID- 28506907
TI  - Validity criteria for the diagnosis of fatty liver by M probe-based controlled
      attenuation parameter.
AB  - BACKGROUND & AIMS: Controlled attenuation parameter (CAP) can be performed
      together with liver stiffness measurement (LSM) by transient elastography (TE)
      and is often used to diagnose fatty liver. We aimed to define the validity
      criteria of CAP. METHODS: CAP was measured by the M probe prior to liver biopsy
      in 754 consecutive patients with different liver diseases at three centers in
      Europe and Hong Kong (derivation cohort, n=340; validation cohort, n=414; 101
      chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver
      disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3
      4; age 52+/-14; body mass index 27.2+/-5.3kg/m2). The primary outcome was the
      diagnosis of fatty liver, defined as steatosis involving >=5% of hepatocytes.
      RESULTS: The area under the receiver-operating characteristics curve (AUROC) for
      CAP diagnosis of fatty liver was 0.85 (95% CI 0.82-0.88). The interquartile range
      (IQR) of CAP had a negative correlation with CAP (r=-0.32, p<0.001), suggesting
      the IQR-to-median ratio of CAP would be an inappropriate validity parameter. In
      the derivation cohort, the IQR of CAP was associated with the accuracy of CAP
      (AUROC 0.86, 0.89 and 0.76 in patients with IQR of CAP <20 [15% of patients], 20
      39 [51%], and >=40dB/m [33%], respectively). Likewise, the AUROC of CAP in the
      validation cohort was 0.90 and 0.77 in patients with IQR of CAP <40 and >=40dB/m,
      respectively (p=0.004). The accuracy of CAP in detecting grade 2 and 3 steatosis
      was lower among patients with body mass index >=30kg/m2 and F3-4 fibrosis.
      CONCLUSIONS: The validity of CAP for the diagnosis of fatty liver is lower if the
      IQR of CAP is >=40dB/m. Lay summary: Controlled attenuation parameter (CAP) is
      measured by transient elastography (TE) for the detection of fatty liver. In this
      large study, using liver biopsy as a reference, we show that the variability of
      CAP measurements based on its interquartile range can reflect the accuracy of
      fatty liver diagnosis. In contrast, other clinical factors such as adiposity and
      liver enzyme levels do not affect the performance of CAP.

PMID- 28506908
TI  - Effects of the fibroblast activation protein inhibitor, PT100, in a murine model
      of pulmonary fibrosis.
AB  - Bleomycin (BLM) induced lung injury is detectable in C57BL/6 mice using magnetic
      resonance imaging (MRI). We investigated the effects of the fibroblast activation
      protein (FAP) inhibitor, PT100, in this model. BLM (0.5mg/kg/day) was
      administered on days -7, -6, -5, -2, -1, 0 in the nostrils of male mice. PT100
      (40ug/mouse) or vehicle (0.9%NaCl) was dosed per os twice daily from day 1-14.
      MRI was performed before BLM and at days 0, 7 and 14. After the last MRI
      acquisition, animals were euthanised and the lungs harvested for histological and
      quantitative real-time polymerase chain reaction (qRT-PCR) analyses. As evidenced
      longitudinally by MRI, the BLM-elicited lesions in the lungs of vehicle-treated
      mice progressed over time. In contrast, responses elicited by BLM did not
      progress in animals receiving PT100. Histology demonstrated significant less
      fibrosis in PT100- than in vehicle-treated, BLM-challenged mice. Significant
      correlation (R=0.91, P<0.001, N=24) was found between the volumes of BLM-induced
      lesions detected in vivo by MRI and the collagen content determined
      histologically (picrosirius staining). FAP was overexpressed in the lungs of BLM
      challenged mice. Upon PT100 treatment, FAP expression was reduced. Significant
      differences in the MMP-12, MIP-1alpha, and MCP-3 mRNA expression levels in the
      lungs of PT100- compared to vehicle-treated mice were also revealed by qRT-PCR.
      The IBA-1 level determined histologically was higher in the lungs of PT100-
      compared to vehicle-treated mice. Taken together, these observations suggest that
      treatment with PT100 in this murine model of pulmonary fibrosis had an anti-fibro
      proliferative effect and increased macrophage activation.

PMID- 28506909
TI  - The selective effect of glycyrrhizin and glycyrrhetinic acid on topoisomerase
      IIalpha and apoptosis in combination with etoposide on triple negative breast
      cancer MDA-MB-231 cells.
AB  - Triple negative breast cancer(TNBC) has generated growing interests due to its
      aggressive biologic behavior and absence of targeted therapy approach.
      Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA)
      have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA
      have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition
      of cell proliferation, GA at non-cytotoxic concentration showed synergistic
      effect in combination with anti-cancer drug, etoposide(VP-16). Specifically, GA
      enhanced cytotoxicity through regulating topoisomerase IIalpha(TOPO 2A) targeted
      by etoposide. GA sensitized the cells to etoposide through elevating TOPO 2A with
      a 2.4 fold rate at 12h. From 12 to 48h, GA halved the expression of TOPO 2A and
      stimulated apoptosis, which exhibited its antineoplastic effect. Our experiments
      showed that GSH depletion, modulation of MAPK and AKT pathways accounted for the
      regulation of topoisomerase IIalpha and apoptosis. However, GL showed protection
      and detoxication by decreasing reactive oxygen species generation, maintaining
      GSH and differentially modulating apoptosis, AKT pathway, ERK and JNK of MAPK
      pathway. Collectively, our results demonstrate that GA, instead of GL, is a
      better candidate for TNBC treatment because of its anti-cancer effect and
      sensitization of topoisomerase IIalpha inhibitor.

PMID- 28506910
TI  - Omecamtiv mecarbil activates ryanodine receptors from canine cardiac but not
      skeletal muscle.
AB  - Due to the limited results achieved in the clinical treatment of heart failure, a
      new inotropic strategy of myosin motor activation has been developed. The lead
      molecule of myosin activator agents is omecamtiv mecarbil, which binds directly
      to the heavy chain of the cardiac beta-myosin and enhances cardiac contractility
      by lengthening the lifetime of the acto-myosin complex and increasing the number
      of the active force-generating cross-bridges. In the absence of relevant data,
      the effect of omecamtiv mecarbil on canine cardiac ryanodine receptors (RyR 2)
      has been investigated in the present study by measuring the electrical activity
      of single RyR 2 channels incorporated into planar lipid bilayer. When applying
      100nM Ca2+ concentration on the cis side ([Ca2+]cis) omecamtiv mecarbil (1-10uM)
      significantly increased the open probability and opening frequency of RyR 2,
      while the mean closed time was reduced. Mean open time was increased moderately
      by 10uM omecamtiv mecarbil. When [Ca2+]cis was elevated to 322 and 735nM, the
      effect of omecamtiv mecarbil on open probability was evident only at higher (3
      10uM) concentrations. All effects of omecamtiv mecarbil were fully reversible
      upon washout. Omecamtiv mecarbil (up to 10uM) had no effect on the open
      probability of RyR 1, isolated from either canine or rabbit skeletal muscles. It
      is concluded that the direct stimulatory action of omecamtiv mecarbil on RyR 2
      has to be taken into account when discussing the mechanism of action or the
      potential side effects of the compound.

PMID- 28506911
TI  - Mangiferin protects against ?intestinal ischemia/reperfusion-induced ?liver
      injury: ??Involvement of PPAR-?gamma, GSK-3beta and Wnt/beta-catenin
      pathway????????????????????????????????????????????????.
AB  - AIM: Mangiferin (MF), a xanthonoid from Mangifera indica, possesses anti
      inflammatory, immunomodulatory, and potent antioxidant effects; however, its
      protective effect against mesenteric ischemia/reperfusion (I/R)-induced liver
      injury has not been fully clarified. The study was designed to assess the
      possible mechanism of action of MF against mesenteric I/R model. MAIN METHODS:
      Male Wister rats were treated with MF (20mg/kg, i.p) or the vehicle for 3 days
      before I/R, which was induced by clamping the superior mesenteric artery for
      30min followed by declamping for 60min. KEY FINDINGS: The mechanistic studies
      revealed that MF protected the 2 organs studied, viz., liver and intestine partly
      via increasing the content of beta-catenin and PPAR-gamma along with decreasing
      that of GSK-3beta and the phosphorylated NF-?B-p65. MF antioxidant effect was
      evidenced by increasing contents of total antioxidant capacity and GST, besides
      normalizing that of MDA. Regarding the anti-inflammatory effect, MF reduced IL
      1beta and IL-6, effects that were mirrored on the tissue content of MPO.
      Moreover, MF possessed anti-apoptotic character evidenced by elevating Bcl-2
      content and reducing that of caspase-3. In the serum, intestinal I/R increased
      the activity of ALT, AST, and creatine kinase. SIGNIFICANCE: The intimated
      protective mechanisms of MF against mesenteric I/R are mediated, partially, by
      modulation of oxidative stress, inflammation, and apoptosis possibly via the
      involvement of Wnt/beta-catenin/NF-?beta/ PPAR-gamma signaling pathways.

PMID- 28506912
TI  - Characterization and comparison of SGLT2 inhibitors: Part 3. Effects on diabetic
      complications in type 2 diabetic mice.
AB  - In this study, we investigated and compared the effects of all six sodium-glucose
      cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes
      related diseases and complications in type 2 diabetic mice. Following 4-week
      repeated administration to diabetic mice, all SGLT2 inhibitors showed significant
      improvement in diabetes-related diseases and complications, including obesity;
      abnormal lipid metabolism; steatohepatitis; inflammation; endothelial
      dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable
      effects in reducing hyperglycemia, improvement of these diabetes-related diseases
      and complications was more potent with the two long-acting drugs (ipragliflozin
      and dapagliflozin) than with the four intermediate-acting four drugs
      (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without
      statistical significance. These findings demonstrate that SGLT2 inhibitors
      alleviate various diabetic pathological conditions in type 2 diabetic mice, and
      suggest that SGLT2 inhibitors, particularly long-acting drugs, might be useful
      not only for hyperglycemia but also in diabetes-related diseases and
      complications, including nephropathy in type 2 diabetes.

PMID- 28506914
TI  - Compliant endovascular balloon reduces the lethality of superior vena cava tears
      during transvenous lead extractions.
AB  - BACKGROUND: Superior vena cava (SVC) lacerations have been identified as the most
      lethal complication encountered during cardiac implantable electronic device lead
      extraction. The case fatality rate of these events approximates 50% due to rapid
      exsanguination. A novel, compliant balloon specifically designed for use in the
      SVC may provide hemostasis in the event of endovascular perforation. By
      temporarily occluding the compromised vessel, the endovascular balloon should
      delay hemodynamic collapse, provide a more controlled surgical field for repair,
      and thereby reduce the mortality of SVC tears complicating transvenous lead
      extraction. OBJECTIVE: To assess the early impact of the compliant endovascular
      balloon on the management of SVC tears and survival outcomes. METHODS: We
      searched a publicly available, United States Food and Drug Administration
      maintained database for adverse events from 1 manufacturer of lead extraction
      tools. Reports from July 1, 2016, to December 31, 2016 were reviewed by 2
      physicians to identify instances of SVC tears. Extracting physicians were
      contacted for further case details. Confirmed SVC tears were analyzed for patient
      demographics, repair strategies, and index hospitalization mortality. RESULTS: Of
      the complications reported, 35 cases of surgically confirmed SVC tears were
      identified. One hundred percent of patients (9/9) were discharged alive when the
      endovascular balloon was properly utilized, compared to 50% of patients (13/26)
      when the device was not used (P = .0131). Differences between all other variables
      analyzed were statistically insignificant. CONCLUSION: During the study period,
      we observed a reduction in mortality in patients who suffered SVC tears while
      undergoing lead extraction when treatment included an endovascular balloon.

PMID- 28506913
TI  - Predicting Determinants of Atrial Fibrillation or Flutter for Therapy Elucidation
      in Patients at Risk for Thromboembolic Events (PREDATE AF) Study.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common clinically significant
      cardiac rhythm disorder. There is considerable interest in screening for AF, as
      it is a leading cause of stroke, and oral anticoagulants (OACs) have been shown
      to significantly reduce the risk of stroke in patients with AF. Improved
      screening for AF with subsequent treatment may help improve long-term outcomes,
      but the optimal patient population and screening intensity are unknown.
      OBJECTIVES: In this study, we prospectively evaluated the use of the CHA2DS2-VASc
      score for the prediction of new-onset AF using insertable cardiac monitors (ICMs)
      and examined whether this screening led to the initiation of OAC therapy.
      METHODS: We enrolled 245 subjects with no history of AF and CHA2DS2-VASc score
      >=2 to be screened for AF with an ICM. The ICMs were programmed to record AF
      episodes >=6 minutes in duration. Subjects were followed for 18 months with
      monthly remote interrogations and all events adjudicated by cardiologists. In
      subjects diagnosed with AF, medical records were reviewed to determine subsequent
      care. RESULTS: During a mean follow-up of 451 +/- 185 days, the incidence of AF
      was 22.4% (95% confidence interval 17.2%-27.7%) with a mean time to detection of
      141.3 +/- 139.5 days. Among subjects newly diagnosed with AF, 76.4% were
      prescribed anticoagulation with either a novel OAC (n = 38) or warfarin (n = 4).
      CONCLUSION: In this large prospective cohort of subjects with CHA2DS2-VASc scores
      >=2, 22.4% were newly diagnosed with AF and the majority of these subjects were
      given OACs, suggesting a potential role of ICMs in AF screening.

PMID- 28506915
TI  - Long QT syndrome: Who needs a transplant?

PMID- 28506918
TI  - Cardiac resynchronization therapy using permanent His-bundle pacing: Are we there
      yet?

PMID- 28506917
TI  - Atrial antitachycardia pacing and atrial remodeling: A substudy of the
      international, randomized MINERVA trial.
AB  - BACKGROUND: Atrial tachycardia (AT) and atrial fibrillation (AF) are common in
      pacemaker patients and are associated with bad prognoses. OBJECTIVE: The purpose
      of this study was to evaluate atrial antitachycardia pacing impact on AT/AF
      induced atrial remodeling, measured by early recurrence of AT/AF (ERAF) and by
      change in left atrial diameter (LAD), and to evaluate the impact of AT/AF
      duration on ERAF incidence. METHODS: Pacemaker patients were randomized to dual
      chamber pacing (Control DDDR: 385 patients), managed ventricular pacing (MVP: 398
      patients), or atrial antitachycardia pacing plus MVP (DDDRP+MVP: 383 patients).
      LAD change, estimated by echocardiography, was considered significant if the
      relative difference between baseline and 24-month measurements was >10%. RESULTS:
      At median follow-up of 34 months, ERAF incidence was significantly lower in the
      DDDRP+MVP arm for all AT/AF durations, in particular, ERAF followed AT/AF longer
      than 3 hours in 53% cases in Control DDDR, in 51% cases in MVP, and in 39% cases
      in DDDRP+MVP (P <.001 vs other groups). ERAF incidence showed a U-shaped pattern
      when evaluated as a function of previous AT/AF duration, decreasing for durations
      from 5 minutes to 12 hours and increasing for longer durations. Among patients
      with significant LAD change, the proportion of patients with a reduction in LAD
      was 35% in Control DDDR, 37% in MVP, and 70% in DDDRP+MVP (P <.05 vs other
      groups). CONCLUSION: Our data suggest that atrial electrical remodeling becomes
      important after about 12 hours of continuous arrhythmia. Compared to DDDR or MVP,
      DDDRP+MVP reduces ERAF and favors LAD reduction, suggesting that atrial
      antitachycardia pacing may reverse electrical and mechanical remodeling.

PMID- 28506919
TI  - Novel dyeless and fluoro-less approach to cryoballoon pulmonary vein occlusion
      assessment.
AB  - BACKGROUND: Pulmonary vein (PV) occlusion is essential for PV isolation (PVI)
      using the cryoballoon. Currently occlusion is arbitrarily determined using
      fluoroscopy and contrast media. This study aimed to create an objective measure
      without utilizing excessive fluoroscopy and using no contrast media. OBJECTIVE:
      To ensure PV occlusion without fluoroscopy and contrast dye. METHODS: In 4 in
      vivo hearts 113 PV occlusions were tested with a 50% cold dye saline mix at 4
      degrees C. Occlusions were rated Good, Fair, and Poor by dye dissipation seen via
      fluoroscopy and correlated to temperature profiles recorded concurrently. Using
      these temperature profiles and no dye, cryoablations were placed in 12 additional
      hearts (56 unique veins, 126 occlusions). Two 180-second cryoablation
      applications were placed per vein with occlusion testing in between. PVI was
      defined by electrophysiology mapping, gross pathology, and histology after >=4
      weeks recovery. RESULTS: Dye results were as follows: With Good, Fair, and Poor
      the maximal postinjection PV temperature dropped (DeltaT) by 6.2 +/- 4.2 degrees
      C, 5.1 +/- 3.7 degrees C, and 2.4 +/- 2.0 degrees C. At 5 seconds post nadir
      temperature, injection temperature recovered 18% +/- 14%, 36% +/- 23%, and 50% +/
      33%. Console thaw time to 0 degrees C was 11.5 +/- 4.8 seconds, 8.5 +/- 2.1
      seconds, and 4.3 +/- 1.3 seconds. Success rate for PVI was 100%, 97%, and 0%.
      With no dye: DeltaT: 7.7 +/- 4.4 degrees C, 5.8 +/- 5.0 degrees C, and 3.4 +/-
      2.3 degrees C; % recovery at 5 seconds: 15% +/- 12%, 31% +/- 23%, 45% +/- 30%;
      thaw time to 0 degrees C: 11.9 +/- 4.8 seconds, 10.5 +/- 5.2 seconds, 6.0 +/- 2.8
      seconds; success rate: 97%, 91%, and 10%. CONCLUSION: PV occlusion profile
      determination using 4 degrees C cold saline injection is an effective approach to
      define the occlusion grade. Quality occlusions correlate strongly with PVI
      success.

PMID- 28506920
TI  - Regulatory B cells in rheumatoid arthritis: Alterations in patients receiving
      anti-TNF therapy.
AB  - : Cytokines, including tumor necrosis factor alpha (TNFalpha) are involved in
      Rheumatoid arthritis (RA) pathogenesis by augmenting autoimmunity, sustaining
      long term inflammation in the synovium, and promoting joint damage. Anti-TNF
      therapy is one of the most efficient and widely used therapies for RA, although
      its mechanism is not clarified yet. Earlier we demonstrated that RA patients have
      a reduced number of IL-10 producing regulatory B cells (B10 cells) as compared to
      healthy individuals and they are functionally impaired. Our aim was to study the
      influence of anti-TNF therapy on B10 cells in RA, to follow the alteration of B
      cell activation markers (CD25, CD69) and to monitor the level of citrullinated
      peptid-specific antibodies and the secreted IL-10 in patients' sera during the
      therapy. We have observed that at six month after starting the therapy the
      frequency of B10 cells remarkably increased, while the expression of the
      activation marker, CD69 decreased on B cells. In contrast, serum levels of IL-10
      and anti-citrullinated peptide antibodies did not change post-treatment.
      CONCLUSION: The reduced activation state of B cells and the increasing number of
      regulatory B10. cells might contribute to the therapeutic efficacy of anti-TNF
      agents in RA.

PMID- 28506921
TI  - Decrease of blood anti-alpha1,3 Galactose Abs levels in multiple sclerosis (MS)
      and clinically isolated syndrome (CIS) patients.
AB  - The etiology of multiple sclerosis (MS) remains elusive. Among the possible
      causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of
      Infectious mononucleosis (IMN) may damage the integrity of the blood-brain
      barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell
      clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti
      alpha1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated
      syndrome (CIS) patients, as well as age/gender-matched healthy individuals. Anti
      Gal and anti-Neu5Gc are significantly increased during IMN (p=0.02 and p<1.10-4
      respectively), but not in acute CMV primo-infection. We show that, whereas there
      was no change in anti-Neu5Gc in MS/CIS, the two populations exhibit a significant
      decrease in anti-Gal (combined p=2.7.10-3), in contrast with patients with non
      MS/CIS central nervous system pathologies. Since anti-Gal result from an
      immunization against alpha1,3 Gal, lacking in humans but produced in the gut, our
      data suggest that CIS and MS patients have an altered microbiota or an altered
      response to this microbiotic epitope.

PMID- 28506923
TI  - Core, social and moral disgust are bounded: A review on behavioral and neural
      bases of repugnance in clinical disorders.
AB  - Disgust is a multifaceted experience that might affect several aspects of life.
      Here, we reviewed research on neurological and psychiatric disorders that are
      characterized by abnormal disgust processing to test the hypothesis of a shared
      neurocognitive architecture in the representation of three disgust domains: i)
      personal experience of 'core disgust'; ii) social disgust, i.e., sensitivity to
      others' expressions of disgust; iii) moral disgust, i.e., sensitivity to ethical
      violations. Our review provides some support to the shared neurocognitive
      hypothesis and suggests that the insula might be the "hub" structure linking the
      three domains of disgust sensitivity, while other brain regions may subserve
      specific facets of the multidimensional experience. Our review also suggests a
      role of serotonin core and moral disgust, supporting "neo-sentimentalist"
      theories of morality, which posit a causal role of affect in moral judgment.

PMID- 28506924
TI  - Olfactory and gustatory functions in bipolar disorders: A systematic review.
AB  - Olfactory and gustatory dysfunctions have been described in different psychiatric
      disorders. Several studies have found gustatory and olfactory function change in
      bipolar disorders with various results. The aim of this study is to have a
      systematic review of studies evaluating gustatory and olfactory function in
      bipolar disorders. After a systematic search, 15 studies on olfaction and 5
      studies on taste were included in this review. The UPSIT (University of
      Pennsylvania Smell Identification Test) and Sniffin' Sticks were the most widely
      used tests to evaluate smell. Some studies on olfaction described dysfunctions in
      smell identification as potential markers for bipolar disorders. Moreover,
      olfactory acuity was associated with psychosocial and cognitive performances. For
      taste, only few studies used standardized tests to evaluate gustation. These
      studies showed that patients with Bipolar disorders had more gustatory
      dysfunction compared to controls, and to non-bipolar depressed patients.

PMID- 28506925
TI  - Social connectedness, mental health and the adolescent brain.
AB  - Social relationships promote health and wellbeing. Brain regions regulating
      social behavior continue to develop throughout adolescence, as teens learn to
      navigate their social environment with increasing sophistication. Adolescence is
      also a time of increased risk for the development of psychiatric disorders, many
      of which are characteristically associated with social dysfunction. In this
      review, we consider the links between adolescent brain development and the
      broader social environment. We examine evidence that individual differences in
      social ability, partly determined by genetic influences on brain structure and
      function, impact the quality and quantity of social ties during adolescence and
      that, conversely, the structure of one's social network exerts complex yet
      profound influences on individual behavior and mental health. In this way, the
      brain and social environment sculpt each other throughout the teenage years to
      influence one's social standing amongst peers. Reciprocal interactions between
      brain maturation and the social environment at this critical developmental stage
      may augment risk or promote resilience for mental illness and other health
      outcomes.

PMID- 28506927
TI  - Connecting minds and sharing emotions through mimicry: A neurocognitive model of
      emotional contagion.
AB  - During social interactions, people tend to automatically align with, or mimic
      their interactor's facial expressions, vocalizations, postures and other bodily
      states. Automatic mimicry might be implicated in empathy and affiliation and is
      impaired in several pathologies. Despite a growing body of literature on its
      phenomenology, the function and underlying mechanisms of mimicry remain poorly
      understood. The current review puts forward a new Neurocognitive Model of
      Emotional Contagion (NMEC), demonstrating how basic automatic mimicry can give
      rise to emotional contagion. We combine neurological, developmental and
      evolutionary insights to argue that automatic mimicry is a precursor to healthy
      social development. We show that (i) strong synchronization exists between
      people, (ii) that this resonates on different levels of processing and (iii)
      demonstrate how mimicry translates into emotional contagion. We conclude that our
      synthesized model, built upon integrative knowledge from various fields, provides
      a promising avenue for future research investigating the role of mimicry in human
      mental health and social development.

PMID- 28506922
TI  - Oxytocin effects in schizophrenia: Reconciling mixed findings and moving forward.
AB  - Schizophrenia is a severe mental illness that causes major functional impairment.
      Current pharmacologic treatments are inadequate, particularly for addressing
      negative and cognitive symptoms of the disorder. Oxytocin, a neuropeptide known
      to moderate social behaviors, has been investigated as a potential therapeutic
      for schizophrenia in recent years. Results have been decidedly mixed, leading to
      controversy regarding oxytocin's utility. In this review, we outline several
      considerations for interpreting the extant literature and propose a focused
      agenda for future work that builds on the most compelling findings regarding
      oxytocin effects in schizophrenia to date. Specifically, we examine underlying
      causes of heterogeneity in randomized clinical trials (RCTs) conducted thus far
      and highlight the complexity of the human oxytocin system. We then review
      evidence of oxytocin's effects on specific deficits in schizophrenia, arguing for
      further study using objective, precise outcome measures in order to determine
      whether oxytocin has the potential to improve functional impairment in
      schizophrenia.

PMID- 28506928
TI  - Distinct phosphodiesterase 5A-containing compartments allow selective regulation
      of cGMP-dependent signalling in human arterial smooth muscle cells.
AB  - Cyclic GMP (cGMP) translates and integrates much of the information encoded by
      nitric oxide (NO.) and several natriuretic peptides, including the atrial
      natriuretic peptide (ANP). Previously, we reported that integration of a cGMP
      specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A
      (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor
      (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control
      of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER
      Ca2+ in human platelets. Herein, we report that PDE5A integrates into an
      analogous signalosome in human arterial smooth muscle cells (HASMC), wherein it
      regulates muscarinic agonist-dependent Ca2+ release and is activated selectively
      by PKG-dependent phosphorylation. In addition, we report that PDE5A also
      regulates HASMC functions via events independent of PKG, but rather through
      actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by
      the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A).
      Indeed, we show that ANP increases both cGMP and cAMP levels in HASMC and
      promotes phosphorylation of vasodilator-stimulated phospho-protein (VASP) at each
      the PKG and PKA phospho-acceptor sites. Since selective inhibition of PDE5
      decreased DNA synthesis and chemotaxis of HASMC, and that PDE3A knockdown
      obviated these effects, our findings are consistent with a role for a PDE5A-PDE3A
      PKA axis in their regulation. Our findings provide insight into the existence of
      distinct "pools" of PDE5A in HASMC and support the idea that these discrete
      compartments regulate distinct cGMP-dependent events. As a corollary, we suggest
      that it may be possible to target these distinct PDE5A-regulated pools and in so
      doing differentially impact selected cGMP-regulated functions in these cells.

PMID- 28506926
TI  - High times for cannabis: Epigenetic imprint and its legacy on brain and behavior.
AB  - Extensive debates continue regarding marijuana (Cannabis spp), the most commonly
      used illicit substance in many countries worldwide. There has been an exponential
      increase of cannabis studies over the past two decades but the drug's long-term
      effects still lack in-depth scientific data. The epigenome is a critical
      molecular machinery with the capacity to maintain persistent alterations of gene
      expression and behaviors induced by cannabinoids that have been observed across
      the individual's lifespan and even into the subsequent generation. Though
      mechanistic investigations regarding the consequences of developmental cannabis
      exposure remain sparse, human and animal studies have begun to reveal specific
      epigenetic disruptions in the brain and the periphery. In this article, we focus
      attention on long-term disturbances in epigenetic regulation in relation to
      prenatal, adolescent and parental germline cannabinoid exposure. Expanding
      knowledge about the protracted molecular memory could help to identify novel
      targets to develop preventive strategies and treatments for behaviors relevant to
      neuropsychiatric risks associated with developmental cannabis exposure.

PMID- 28506929
TI  - Inhibition of cell proliferation and induction of autophagy by KDM2B/FBXL10
      knockdown in gastric cancer cells.
AB  - Gastric cancer is difficult to cure due to its clinical heterogeneity and the
      complexity of its molecular mechanisms. KDM2B, a member of the JHDM family,
      functions as a histone lysine demethylase. However, the role and mechanisms of
      KDM2B in gastric cancer have not been elucidated. Here, we showed that KDM2B is
      commonly expressed in gastric cancer cells. The downregulation of KDM2B
      immediately induces autophagy, followed by the inhibition of proliferation. The
      compound 3-methyladenine (3-MA), an inhibitor of autophagy, largely rescues
      autophagy and the inhibition of cell proliferation induced by KDM2B knockdown. In
      this process, we observed a downregulation of the phosphorylation of Akt and its
      downstream effectors mTOR and p70S6K and an upregulation of Erk phosphorylation
      after KDM2B knockdown. In a xenograft model, the downregulation of KDM2B can
      inhibit tumour growth. The conversion of LC3-I to LC3-II also decreased
      concomitantly in vivo, which is a hallmark of autophagy. Taken together, our
      study was the first to demonstrate a novel regulatory role of KDM2B in autophagy
      and cell growth in gastric cancer cells. Our findings suggest that KDM2B may
      serve as a novel therapeutic target for gastric cancer therapy.

PMID- 28506931
TI  - In vitro affinity of Deinococcus radiodurans MutS towards mismatched DNA exceeds
      that of its orthologues from Escherichia coli and Thermus thermophilus.
AB  - The mismatch binding protein MutS is responsible for the recognition of mispaired
      and unpaired bases, which is the initial step in DNA repair. Among the MutS
      proteins most extensively studied in vitro are those derived from Thermus
      thermophilus, Thermus aquaticus and Escherichia coli. Here, we present the first
      report on the in vitro examination of DNA mismatch binding activity of MutS
      protein from Deinococcus radiodurans and confront this with the properties of
      those from E. coli and T. thermophilus. The analyses which included mobility gel
      shift assay, colorimetric and qPCR estimation of MutS-bound DNA clearly showed
      that D. radiodurans MutS exhibited much higher affinity towards mismatched DNA in
      vitro than its counterparts from E. coli and T. thermophilus. In addition, D.
      radiodurans MutS displayed a significantly higher specificity of DNA mismatch
      binding than the two other orthologues. The specificity expressed as the ratio of
      mismatched to fully complementary DNA bound reached over 4 and 20-fold higher
      values for D. radiodurans than for T. thermophilus and E. coli MutS,
      respectively. The results demonstrate mainly the biotechnological potential of D.
      radiodurans MutS but the in vitro characteristics of the MutS orthologues could
      reflect substantial differences in DNA mismatch binding activities existing in
      vivo.

PMID- 28506930
TI  - Rewiring the reductive tricarboxylic acid pathway and L-malate transport pathway
      of Aspergillus oryzae for overproduction of L-malate.
AB  - Aspergillus oryzae finds wide application in the food, feed, and wine industries,
      and is an excellent cell factory platform for production of organic acids. In
      this work, we achieved the overproduction of L-malate by rewiring the reductive
      tricarboxylic acid (rTCA) pathway and L-malate transport pathway of A. oryzae
      NRRL 3488. First, overexpression of native pyruvate carboxylase and malate
      dehydrogenase in the rTCA pathway improved the L-malate titer from 26.1gL-1 to
      42.3gL-1 in shake flask culture. Then, the oxaloacetate anaplerotic reaction was
      constructed by heterologous expression of phosphoenolpyruvate carboxykinase and
      phosphoenolpyruvate carboxylase from Escherichia coli, increasing the L-malate
      titer to 58.5gL-1. Next, the export of L-malate from the cytoplasm to the
      external medium was strengthened by overexpression of a C4-dicarboxylate
      transporter gene from A. oryzae and an L-malate permease gene from
      Schizosaccharomyces pombe, improving the L-malate titer from 58.5gL-1 to 89.5gL
      1. Lastly, guided by transcription analysis of the expression profile of key
      genes related to L-malate synthesis, the 6-phosphofructokinase encoded by the pfk
      gene was identified as a potential limiting step for L-malate synthesis.
      Overexpression of pfk with the strong sodM promoter increased the L-malate titer
      to 93.2gL-1. The final engineered A. oryzae strain produced 165gL-1 L-malate with
      a productivity of 1.38gL-1h-1 in 3-L fed-batch culture. Overall, we constructed
      an efficient L-malate producer by rewiring the rTCA pathway and L-malate
      transport pathway of A. oryzae NRRL 3488, and the engineering strategy adopted
      here may be useful for the construction of A. oryzae cell factories to produce
      other organic acids.

PMID- 28506932
TI  - Refined annotation of the complete genome of the phytopathogenic and xanthan
      producing Xanthomonas campestris pv. campestris strain B100 based on RNA sequence
      data.
AB  - Bioinformatics tools and gene expression data were applied to identify new genes
      and to enhance the accuracy in genomic feature predictions for Xanthomonas
      campestris pv. campestris (Xcc) B100, a pathogen of cruciferous plants and model
      strain for the biosynthesis of xanthan, a polysaccharide with a multitude of
      commercial applications as a thickening agent. Results from 5'-enriched end RNA
      sequencing (RNA-seq) and total transcriptome RNA-seq experiments were used for
      this purpose. Functional gene annotations were updated where new evidence had
      emerged and start codon predictions were enhanced for 153 protein-coding genes
      (CDS). In total, 32 novel CDS, and 176 novel RNA genes and features were
      predicted, among them 77 isogenes of the small non-coding RNA sX9. Furthermore,
      the RNA-seq data facilitated the identification of 848 operons that included a
      total of 2551 CDS besides 1667 CDS that were mono-cistronically expressed.

PMID- 28506933
TI  - Effective estimation of the minimum number of amino acid residues required for
      functional divergence between duplicate genes.
AB  - One of hot research foci has always been predicting amino acid residues
      underlying functional divergence after gene duplication, as those predicted sites
      can be used as candidates for further functional experimentations. It is
      important and interesting to know how many sites, on average, may have been
      responsible for the functional divergence between duplicate genes. In this
      article, we studied two basic types of functional divergence (type-I and type-II)
      in depth in order to give an accurate estimation of functional divergence-related
      sites. Type-I divergences result from altered functional constraints (i.e.,
      different evolutionary rates) between duplicate genes, whereas type-II
      divergences refer to residues that are conserved by functional constraints but
      exhibit different physicochemical properties (e.g., charge or hydrophobicity)
      between duplicates. An effective site number (NE) strategy was applied in our
      study, which implements a stepwise regression model to calculate the minimum
      number of residues responsible for functional divergence without choosing preset
      threshold. We found that NE-determined cut-off value varies among different
      duplicate pairs, suggesting that empirical cutoff value is not suitable for every
      case. Under our standard NE calculation method, we estimated less than 15% of
      residues that are required for paralogous gene functional divergence. Finally, we
      established a database, DIVERGE-D, as a public resource for the predicted NE
      sites between two paralogs in this study, which can be used as candidates for
      further biological engineering and experimentation.

PMID- 28506935
TI  - Retrosynthesis of CaCO3 via amorphous precursor particles using gastroliths of
      the Red Claw lobster (Cherax quadricarinatus).
AB  - Gastroliths are highly calcified structures formed in the cardiac stomach wall of
      crustaceans for the temporary storage of amorphous CaCO3 (ACC). The gastrolithic
      ACC is stabilized by the presence of biomolecules, and represents a novel model
      for research into biomineralization. For the first time, an in vitro biomimetic
      retrosynthesis of scaffolds of gastrolithic matrices with CaCO3 is presented.
      With the help of synthetic polyacrylic (PAA) and phytic (PA) acids, amorphous
      precursor particles were stabilized in double (DD) and gas (GD) diffusion
      crystallization assays. The presence of these synthetic molecules as efficient
      inhibitors of nucleation and growth of CaCO3, and the use of biological
      gastrolith scaffolds as confined reaction environments determined the kinetics of
      crystallization, and controlled the morphogenesis of CaCO3. The formation of ACC
      particles was demonstrated and their crystallization was followed by light
      microscopy, scanning and transmission electron microscopy, and electron
      diffraction.

PMID- 28506934
TI  - Dynamic Regulation of DELLA Protein Activity: SPINDLY and SECRET AGENT Unmasked!

PMID- 28506936
TI  - Assessment of long-term mortality in patients with complex coronary artery
      disease undergoing percutaneous intervention: comparison of multiple anatomical
      and clinical prognostic risk scores.
AB  - AIMS: Three-vessel and left main coronary artery disease (CAD) have important
      prognostic implications. Consequently, numerous risk scores have been developed
      to stratify patients with complex CAD. The aim of the present study was to
      compare the predictive performance of six risk scores for occurrence of fouryear
      all-cause mortality. METHODS AND RESULTS: From March 2008 to December 2012, 348
      consecutive patients with complex CAD undergoing percutaneous coronary
      intervention (PCI) in a tertiary centre in Sao Paulo, Brazil, were analysed. Four
      year mortality was assessed. The scores compared were: baseline SYNTAX score
      (SS), residual SYNTAX score (rSS), ACEF score, clinical SYNTAX score (cSS),
      SYNTAX revascularisation index (SRI) and SYNTAX score II (SSII). SSII had the
      best predictive performance, AUC 0.82, Brier score 0.10, surpassing all the other
      scores for long-term mortality prediction. Moreover, SSII discriminated well PCI
      patients in risk groups with p<0.01 for four-year all-cause mortality. The ACEF
      score (AUC 0.77) and the cSS (AUC 0.78) were significantly better than the SS
      (AUC 0.65), SRI (AUC 0.60) or the rSS (AUC 0.55). CONCLUSIONS: For patients with
      complex CAD treated by PCI, the combination of baseline clinical and angiographic
      factors provided better risk assessment. The SSII demonstrated the most precise
      predictive performance for long-term mortality.

PMID- 28506938
TI  - Dynamic transcatheter mitral valve repair: a new concept to treat functional
      mitral regurgitation using an adjustable spacer.
AB  - We report the first-in-man implantation of the Mitra-Spacer. The device was
      implanted transapically. FMR was reduced to moderate. At two months, while in
      NYHA Class II, LVEF had improved, but FMR increased and 2 mL was added, reducing
      FMR to mild. Despite anticoagulation, thrombi developed around the device and the
      valve was replaced at eight months. The Mitra-Spacer successfully bridged this
      patient to surgery after LVEF had recovered.

PMID- 28506937
TI  - Bivalirudin infusion to reduce ventricular infarction: the open-label, randomised
      Bivalirudin Infusion for Ventricular InfArction Limitation (BIVAL) study.
AB  - AIMS: The aim of the study was to investigate whether bivalirudin versus
      unfractionated heparin (UFH) reduces infarct size (IS) for primary percutaneous
      coronary intervention (PPCI) in large acute myocardial infarction (AMI). METHODS
      AND RESULTS: This multicentre open-label trial randomised 78 patients undergoing
      PPCI for large AMI to bivalirudin or UFH. The primary endpoint was IS, assessed
      by cardiac magnetic resonance (CMR) five days after PPCI. Secondary endpoints
      included index of microcirculatory resistance (IMR), CMR-assessed microvascular
      obstruction (MVO) and ejection fraction, and biomarkers for thrombin activity and
      cell injury. No difference was observed in mean IS at five days (25.0+/-19.7 g
      for bivalirudin vs. 27.1+/-20.7 g for UFH; p=0.75). Early MVO was numerically
      lower with bivalirudin (5.3+/-5.8 g vs. 7.7+/-6.3 g; p=0.17), with no significant
      difference in ejection fraction at 90 days (54.6+/-12.0% vs. 49.1+/-12.1%;
      p=0.11). In the biomarkers, thrombin-antithrombin complexes were reduced by 4.8
      ug/L over the first day for bivalirudin versus an increase of 1.9 ug/L in the
      heparin arm (p=0.0003). Acute IMR was lower (43.5+/-21.6 vs. 68.7+/-35.8 mmHg*s,
      respectively; p=0.014). In a planned interim analysis, an approximate 11%
      reduction in IS was observed with bivalirudin; the trial was discontinued for
      futility. CONCLUSIONS: This study did not achieve its primary endpoint of
      significant infarct size reduction in PPCI by prolonged bivalirudin infusion
      compared to UFH, even though complete thrombin inhibition was achieved in the
      acute phase, with a lower myocardial microcirculation resistance at the end of
      the procedure.

PMID- 28506939
TI  - Printed MDCT 3D models for prediction of left atrial appendage (LAA) occluder
      device size: a feasibility study.
AB  - AIMS: Transoesophageal echocardiography (TEE) and multidetector computed
      tomography (MDCT) currently serve as imaging modalities for left atrial appendage
      (LAA) occlusion preprocedural planning. We assessed the feasibility of MDCT-based
      models to predict the correct size of device for LAA occlusion procedures.
      METHODS AND RESULTS: Patients planned for LAA occlusion underwent MDCT before
      implantation, which was used for creating and printing 3D LAA models. Three
      cardiologists evaluated the 3D models and predicted the correct size of the
      device by manual manipulation. These predictions were compared with the actual
      device implanted during the procedure. Twenty-nine patients were included in this
      study. AMPLATZER and WATCHMAN devices were deployed in 12 and 17 patients,
      respectively. Two procedures were aborted due to failure of occlusion; all three
      physicians predicted it. There was good correlation between the 3D models and the
      inserted device for AMPLATZER devices with a concordance correlation coefficient
      of 0.778 (p=0.001) and poor agreement for WATCHMAN devices - concordance
      correlation coefficient of 0.315 (p=0.203). Agreement among the three physicians
      for AMPLATZER and WATCHMAN devices was excellent, with a calculated average intra
      class correlation of 0.915 and 0.816, respectively. CONCLUSIONS: We found LAA
      printed 3D models to be accurate for prediction of LAA occluder device size for
      the AMPLATZER device but not for the WATCHMAN device.

PMID- 28506941
TI  - Left distal transradial access in the anatomical snuffbox for coronary
      angiography (ldTRA) and interventions (ldTRI).
AB  - AIMS: The aim of this technical report is to demonstrate the feasibility of the
      left distal transradial approach for patients in whom left radial access is
      preferred over right radial access for coronary angiography and interventions.
      This procedure is more convenient for the operator. For the right-handed patient,
      the left radial access is more convenient because of the free use of the right
      hand after the procedure. In addition, this technique reduces the chance of
      radial artery occlusion at the site of the distal forearm. METHODS AND RESULTS:
      Coronary access via the left distal radial artery at the anatomical snuffbox
      allows comfortable positioning of the dorsal side of the patient's left hand near
      the right groin. The operator can puncture the artery and perform the coronary
      cannulation at a safe distance from the radiation source and without the need to
      bend over the patient. This technique will be described in detail. Procedural and
      clinical results in the first 70 patients are described. Out of 118 consecutive
      patients assigned to the author's operation programme, 70 patients were
      considered suitable for left distal radial access. There were eight procedural
      failures, requiring crossover to traditional right radial or left radial
      approach. All other procedures were successful, without major discomfort for the
      patient and operator. No radial artery occlusions at the site of the forearm were
      encountered. CONCLUSIONS: Left distal transradial coronary access via the
      anatomical snuffbox, as default technique for patients who need or prefer left
      radial access over right radial access, deserves further exploration.

PMID- 28506940
TI  - COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial
      to assess cooling as an adjunctive therapy to percutaneous intervention in
      patients with acute myocardial infarction.
AB  - AIMS: We aimed to investigate the rapid induction of therapeutic hypothermia
      using the ZOLL Proteus Intravascular Temperature Management System in patients
      with anterior ST-elevation myocardial infarction (STEMI) without cardiac arrest.
      METHODS AND RESULTS: A total of 50 patients were randomised; 22 patients (88%;
      95% confidence interval [CI]: 69-97%) in the hypothermia group and 23 patients
      (92%; 95% CI: 74-99) in the control group completed cardiac magnetic resonance
      imaging at four to six days and 30-day follow-up. Intravascular temperature at
      coronary guidewire crossing after 20.5 minutes of endovascular cooling decreased
      to 33.6 degrees C (range 31.9-35.5 degrees C). There was a 17-minute (95% CI: 4.6
      29.8 min) cooling-related delay to reperfusion. In "per protocol" analysis,
      median infarct size/left ventricular mass was 16.7% in the hypothermia group
      versus 23.8% in the control group (absolute reduction 7.1%, relative reduction
      30%; p=0.31) and median left ventricular ejection fraction (LVEF) was 42% in the
      hypothermia group and 40% in the control group (absolute reduction 2.4%, relative
      reduction 6%; p=0.36). Except for self-terminating paroxysmal atrial fibrillation
      (32% versus 8%; p=0.074), there was no excess of adverse events in the
      hypothermia group. CONCLUSIONS: We rapidly and safely cooled patients with
      anterior STEMI to 33.6 degrees C at the time of coronary guidewire crossing. This
      is >=1.1 degrees C lower than in previous cooling studies. Except for self
      terminating atrial fibrillation, there was no excess of adverse events and no
      clinically important cooling-related delay to reperfusion. A statistically non
      significant numerical 7.1% absolute and 30% relative reduction in infarct size
      warrants a pivotal trial powered for efficacy.

PMID- 28506942
TI  - Insights into the need for permanent pacemaker following implantation of the
      repositionable LOTUS valve for transcatheter aortic valve replacement in 250
      patients: results from the REPRISE II trial with extended cohort.
AB  - AIMS: This analysis aimed to evaluate the incidence and predictors of the need
      for permanent pacemaker (PPM) implantation following implantation of the
      repositionable and fully retrievable LOTUS Aortic Valve Replacement System.
      METHODS AND RESULTS: The prospective, single-arm, multicentre REPRISE II study
      with extended cohort enrolled 250 symptomatic, high surgical risk patients with
      severe aortic stenosis for transfemoral transcatheter aortic valve implantation
      (TAVI) with a 23 mm or 27 mm LOTUS valve. Echocardiography, computed tomography,
      and electrocardiography data were evaluated by independent core labs. Post TAVI,
      32.0% (72/225) of pacemaker-naive patients underwent new PPM implantation at 30
      days. Most (59/72, 82%) patients were implanted for third-degree atrioventricular
      block, and >10% overstretch of the LVOT by area was observed in 59.7% (43/72) of
      PPM patients. Significant independent predictors of PPM at 30 days included
      baseline RBBB (odds ratio [OR] 12.7, 95% CI: 4.5, 36.2; p<0.001) and LVOT
      overstretch >10% (OR 3.4, 95% CI: 1.7, 6.7; p<0.001). There was a trend towards a
      lower 30-day PPM rate in patients with a shallower (<=5 mm) implant depth (23.9%
      <=5 mm vs. 36.9% >5 mm depth from LCS; p=0.06). CONCLUSIONS: Careful attention to
      valve sizing and implant depth may help to reduce the rate of PPM with the LOTUS
      valve.

PMID- 28506943
TI  - Do clinical data and human papilloma virus genotype influence spontaneous
      regression in grade I cervical intraepithelial neoplasia?
AB  - OBJECTIVE: To determine whether medical history, clinical examination and human
      papilloma virus (HPV) genotype influence spontaneous regression in cervical
      intraepithelial neoplasia grade I (CIN-I). MATERIAL AND METHODS: We
      retrospectively evaluated 232 women who were histologically diagnosed as have CIN
      I by means of Kaplan-Meier curves, the pattern of spontaneous regression
      according to the medical history, clinical examination, and HPV genotype.
      RESULTS: Spontaneous regression occurred in most patients and was influenced by
      the presence of multiple HPV genotypes but not by the HPV genotype itself. In
      addition, regression frequency was diminished when more than 50% of the cervix
      surface was affected or when an abnormal cytology was present at the beginning of
      follow-up. CONCLUSION: The frequency of regression in CIN-I is high, making long
      term follow-up and conservative management advisable. Data from clinical
      examination and HPV genotyping might help to anticipate which lesions will
      regress.

PMID- 28506944
TI  - Effect of sacrocolpopexy and retropubic sling on overactive bladder symptoms.
AB  - OBJECTIVE: In this study, we aimed to evaluate the effect of sacrocolpopexy and
      retropubic midurethral sling, or transvaginal tape (TVT) procedure, on overactive
      bladder (OAB) symptoms. Our null hypothesis was that concomitant sacrocolpopexy
      and TVT exacerbate OAB symptoms. MATERIAL AND METHODS: This is a prospective
      cohort study. All subjects had apical/anterior prolapse and underwent robotic
      assisted sacrocolpopexy and TVT, with or without concomitant hysterectomy. All
      subjects completed a standardized one-year follow-up between 2009 and 2014. To
      assess for OAB symptoms, we used the Urogenital Distress Inventory subscale
      questions #15 and/or question #16. Reponses to these questions are based on a
      five-point 0 to 4 Likert scale (0 represents a negative response or no symptoms,
      and 4 represents the most problems). Any patient who answered 1 or higher on the
      Likert scale, either on the frequency or urge incontinence question, was defined
      as having OAB symptoms. RESULTS: Sixty-six subjects completed 12 months of
      visits. Preoperatively, 54 patients (83%) had OAB symptoms, and postoperatively
      29 patients (45%) had OAB symptoms (p<0.001). Patients with postoperative OAB had
      a lower patient global impression of improvement (PGI-I) scores, PGI-I 5.8 with
      OAB, and PGI-I 6.6 without OAB (p<0.003). CONCLUSION: We found that
      sacrocolpopexy and concomitant retropubic midurethral sling does not contribute
      to additive OAB symptoms, and symptoms actually resolved in 38% of women in our
      cohort. The presence of postoperative OAB contributes to lower global impression
      of improvement.

PMID- 28506945
TI  - Urinary fistula-A continuing problem with changing trends.
AB  - OBJECTIVE: Urinary fistula is a distressing complication after difficult vaginal
      deliveries, obstetric, and gynecologic surgeries. The present study describes a
      single center's experience in the management of urinary fistula at a tertiary
      care hospital. It was performed to analyze the etiology of genitourinary fistula,
      to assess the outcome after surgical repair, and to determine the changing trends
      in the etiology and management of urinary fistula. MATERIAL AND METHODS: This
      retrospective study was conducted over 5 years in the department of obstetrics
      and gynecology, All India Institute of Medical Sciences, New Delhi. Twenty
      patients who underwent surgical repair of urinary fistula were included in the
      study and analyzed for their etiology, presentation, site, size, previous failed
      repair, approach of surgical repair, and outcome. The findings of the present
      study were compared with a previous study at our center to determine the changing
      trends of urinary fistula. RESULTS: The mean age of the study population was
      37.05+/-8.08 years. The majority (65%) of the fistulae occurred following
      gynecologic surgeries, whereas 25% were due to obstructed labor, and 10% after
      cesarean section for other indications. The vaginal approach was used in all
      except one case of uterovesical fistula, which was repaired abdominally. The
      outcome was successful in 85% of cases. The success rate was similar in primary
      versus previous failed repair (p=0.270). CONCLUSION: The most common cause of
      urinary fistula in the present study was gynecologic surgery. The vaginal
      approach can be used even in cases with previous failed repairs with a high
      success rate.

PMID- 28506947
TI  - Comparison of bilateral transversus abdominis plane block and wound infiltration
      with bupivacaine for postoperative analgesia after cesarean delivery.
AB  - OBJECTIVE: The study aimed to compare efficacy, safety, pain intensity and
      analgesic consumption in patients receiving either bilateral transversus
      abdominis plane (TAP) block or wound infiltration with bupivacaine after cesarean
      delivery (CD). MATERIAL AND METHODS: A total of 216 parturient women undergoing
      CD under general anesthesia were randomly allocated into five groups: i) controls
      (group 1), ii) TAP placebo (group 2), iii) TAP (group 3), iv) wound infiltration
      placebo (group 4), and, v) wound infiltration (group 5). Pain intensity was
      assessed using a visual analogue scale (VAS). Analgesic consumptions were
      recorded by a blinded nurse at 6, 12, and 18 hours postoperatively. RESULTS: The
      baseline characteristics of the five groups were similar in terms of age, history
      of CD, and body mass indices (p>0.05). There were significant intergroup
      differences in VAS scores between all groups at the zero time-point (p=0.03), at
      the 6th hour (p=0.02), 12th hour (p=0.02), and at the 18th hour (p=0.02). Group 3
      patients had lower pain scores and consumed less diclofenac than group 2 patients
      only within 12 hours postoperatively whereas pain intensity and analgesic
      consumption were not different between group 5 and group 4 patients. Group 5
      patients received significantly less pethidine than group 4 and group 1 patients
      (p<0.001). CONCLUSION: TAP block provided better pain relief and less analgesic
      requirement than bupivacaine wound infiltration early after CD. Given the similar
      amounts of diclofenac but lower amounts of pethidine administered in the wound
      infiltration group, wound infiltration of bupivacaine seems promising in terms of
      reducing opioid use after CD under general anesthesia, especially when TAP block
      is not used.

PMID- 28506946
TI  - Maternal mortality due to hypertensive disorders in pregnancy, childbirth, and
      the puerperium between 2012 and 2015 in Turkey: A nation-based study.
AB  - OBJECTIVE: To analyze maternal deaths in Turkey due to hypertensive disorders.
      MATERIAL AND METHODS: In this retrospective study 812 maternal deaths were
      analyzed. Maternal demographic features, presence of antenatal care, medical and
      obstetric history, mode of delivery, and use emergency antihypertensive therapy
      were recorded. The delay model for each case was investigated. RESULTS:
      Hypertensive disorders accounted for 15.5% (n=126) out of all maternal mortality.
      They were the third most frequent cause among all causes and the 2nd among direct
      causes of maternal deaths. Sixty-one (48.4%) cases were in severe preeclampsia or
      pre-existing hypertensive disorder with increased/superimposed proteinuria, 30.1%
      were in eclampsia, 9.5% cases were diagnosed as hemolysis, elevated liver
      enzymes, low platelet count syndrome, and 11.1% in pre-existing hypertension
      complicating pregnancy, childbirth, and puerperium without increased or
      superimposed proteinuria. The median age was 32 years, 37.3% women were >=35
      years. All deaths except for 2 cases occurred during the postpartum period.
      Twenty-three percent of deaths occurred in the first 48 hours postpartum, and
      51.6% between 8-42 days. Intracranial hemorrhage was the major final cause of
      death with a rate of 41.3%. With the exception of fifteen patients with
      intracranial hemorrhage, emergency antihypertensive agents were not implemented
      in optimal dose and/or duration. A first and/or third delay was identified in
      36.5% of cases. CONCLUSION: Approximately one third of maternal death due to
      hypertensive disorders could be prevented. The importance of acute
      antihypertensive treatment should be emphasized because of most frequent cause of
      death was intracranial hemorrhage.

PMID- 28506948
TI  - Stage IIIC transitional cell carcinoma and serous carcinoma of the ovary have
      similar outcomes when treated with platinum-based chemotherapy.
AB  - OBJECTIVE: Previous studies reported better outcomes for transitional cell
      carcinoma (TCC) of the ovary when compared with more common histologic types such
      as serous epithelial ovarian cancers (EOCs). The aim of this study was to compare
      the survival outcomes of platinum- based chemotherapy in patients with stage IIIC
      TCCs and serous EOCs. MATERIAL AND METHODS: Clinicopathologic features and
      survival data of patients with FIGO stage IIIC TCC and serous EOC who had
      undergone primary surgery followed by six cycles of intravenous platinum/taxane
      between 2007 and 2015 were retrieved from the database of Hacettepe University
      Hospital. RESULTS: We identified 14 (10.9%) TCCs and 114 (89.1%) serous EOCs. The
      median follow-up duration was 28 months (range, 3-101 months). Univariate
      analysis revealed that the TCCs and serous EOCs had similar progression-free
      survival (PFS) and overall survival (OS). Patients with residual disease less
      than 1 cm had longer OS than patients with residual disease greater than 1 cm
      (75.0 vs. 45.0 months, p=0.012). Cox regression analysis of all potential
      prognostic factors showed that the only independent prognostic factor
      significantly associated with OS was residual disease less than 1 cm [hazard
      ratio=0.38; 95% confidence interval: (0.19-0.77); p=0.007]. CONCLUSION:
      Surgically treated advanced stage TCCs did not have a significantly better
      prognosis after platinum/taxane-based chemotherapy when compared with serous
      EOCs. Residual tumor volume after primary surgery was the only independent
      predictor of OS in patients with EOC. Our results demonstrate the significance of
      achieving optimal cytoreduction in all histologic subtypes of EOC.

PMID- 28506949
TI  - Frozen embryo transfer prevents the detrimental effect of high estrogen on
      endometrium receptivity.
AB  - OBJECTIVE: To investigate whether serum levels of estradiol affect reproductive
      outcomes of normoresponder women undergoing fresh embryo transfer (ET) versus
      frozen-thawed ET (FET). MATERIAL AND METHODS: Two hundred fifty-five
      normoresponder women underwent fresh ET in their first or second in vitro
      fertilization cycle. Ninety-two women with negative pregnacy test results
      underwent FET. Clinical and ongoing pregnancy rates, implantation, and live birth
      rates of women undergoing fresh ET versus FET were compared. RESULTS: One hundred
      forty-seven (57.65%) out of the 255 normoresponder women receiving FET had
      positive beta-human chorionic gonadotrophin (hCG) results. The remaining 108
      women had negative beta-hCG results. The clinical pregnancy rates of the fresh ET
      group were found as 55.69% (n=142). Ninety-two of the 108 women with failed
      pregnancies underwent FET; 72.83% had positive beta-hCG results (n=67), and
      70.65% had clinical pregnancy (n=65). Both biochemical and clinical pregnancy
      rates of women undergoing FET increased significantly (p<0.012 and p<0.013,
      respectively). Ongoing pregnancy (60.87% vs. 52.94%) and live birth rates (59.87%
      vs. 48.63%) were similar in both fresh and FET groups. Serum E2 levels of women
      who failed to conceive were significantly higher than those women did conceive.
      Serum progesterone levels of women who conceived versus those that did not were
      similar. CONCLUSION: The detrimental effect of high serum estradiol levels on
      endometrial receptivity could be prevented by FET.

PMID- 28506950
TI  - Fertility sparing approach as the standard of care in young patients with
      immature teratomas.
AB  - Immature teratomas are quite rare tumors arising in young women. They are usually
      diagnosed in early stage and grade and have a good prognosis. In these young
      patients, fertility-sparing management is suggested as the standard of care.
      Bilateral immature teratoma is a rare condition with an incidence of 10%, with a
      five-year survival rate of 80%. The majority of patients received fertility
      sparing treatment followed by adjuvant chemotherapy in 78%. Older age, advanced
      stage, and high grade are negative prognostic factors. The surgery-only, watch
      and-wait approach was evaluated; however, after a median follow-up time of 42
      months, 50% of patients experienced recurrence, but they were successfully
      salvaged with chemotherapy. In a retrospective study, 12 out of 27 patients tried
      to conceive, resulting in 10 pregnancies (8 after chemotherapy). We present a
      narrative review of the current literature regarding the essential
      multidisciplinary approach of such patients in order to achieve the best
      oncologic and fertility-sparing outcome.

PMID- 28506951
TI  - Pharmacokinetic, pharmacodynamic, and clinical aspects of ovulation induction
      agents: A review of the literature.
AB  - Controlled ovarian hyperstimulation is a key step for successful outcomes of
      assisted reproductive technique cycle outcomes. Many medications are available,
      which are commonly useed solely or in combination to achieve multiple follicular
      development. Pharmacokinetic, pharmacodynamic, and clinical information of
      ovulation induction drugs deserve to be elucidated for every individual patient
      before commencing infertility treatment. New concepts and new treatment protocols
      are introduced as ovulation physiology is understood by infertility specialists.
      Increasing treatment success by minimizing aderse effects is a milestone of all
      ovarian stimulation protocols that use these novel interventions. Achievement of
      a satisfactory cycle outcome includes retrieval of sufficient oocytes, a single
      clinical pregnancy, and avoidance of ovarian hyperstimulation syndrome. In this
      review, we evaluate the current literature to determine the most reliable and
      relevant information about the most used ovulation induction drugs.

PMID- 28506952
TI  - Retrospective evaluation of pregnant women with celiac disease.
AB  - OBJECTIVE: To show celiac disease (CD) and its poor pregnancy outcome
      relationship, and to demonstrate the importance of a gluten-free diet together
      with low-dose low-molecular-weight heparin (LMWH) and low-dose corticosteroid
      (LDC) in the management of pregnancies with CD. MATERIAL AND METHODS: This study
      consisted of 2 groups of patients. Six patients with CD (control group) on a
      gluten-free diet were monitored during their first pregnancies within the
      framework of antenatal care program and their pregnancy outcomes were compared
      with eight poorly-treated pregnant patients with CD (study group) who were
      referred from other medical institutions. LMWH (enoxaparine 1x2000 Anti-XA IU/0.2
      mL/day), and LDC (methylprednisolone 1x4 mg p.o/day) were used in the control
      group. Their obstetric histories and outcomes of their last pregnancies were
      compared. The patients' obstetric risk levels were evaluated using the "Beksac
      Obstetrics Index" (BOI). RESULTS: There were miscarriages in 50% of the study
      group. There were also 50% and 75% preterm deliveries in the control and study
      groups, respectively. The BOI of the study group was significantly worse than the
      control group (1.31 vs. 0.31+/-0.21, p<0.01). There were no statistically
      significant differences between age (24+/-4.7 vs 31.7+/-6 years, p=0.448),
      gestational day of birth (259.3+/-8.5 vs 246.6+/-24.3), birthweight (2691+/-698
      vs 2262+/-359 g, p=0.394), and cesarean section rates (p=0.118). CONCLUSION: CD
      is a risk factor for adverse pregnancy outcome. Miscarriage and preterm labor are
      critical complications in pregnancies complicated by CD. A gluten-free diet is
      important in the treatment. LMWH and LDC seem to be helpful in the management of
      pregnant women with CD.

PMID- 28506953
TI  - What is your diagnosis?

PMID- 28506954
TI  - EpxMedTracking: Feasibility Evaluation of an SMS-Based Medication Adherence
      Tracking System in Community Practice.
AB  - BACKGROUND: Medication adherence remains a difficult problem to both assess and
      improve in patients. It is a multifactorial problem that goes beyond the commonly
      cited reason of forgetfulness. To date, eHealth (also known as mHealth and
      telehealth) interventions to improve medication adherence have largely been
      successful in improving adherence. However, interventions to date have used time-
      and cost-intensive strategies or focused solely on medication reminding, leaving
      much room for improvement in using a modality as flexible as eHealth. OBJECTIVE:
      Our objective was to develop and implement a fully automated short message
      service (SMS)-based medication adherence system, EpxMedTracking, that reminds
      patients to take their medications, explores reasons for missed doses, and alerts
      providers to help address problems of medication adherence in real time. METHODS:
      EpxMedTracking is a fully automated bidirectional SMS-based messaging system with
      provider involvement that was developed and implemented through Epharmix, Inc.
      Researchers analyzed 11 weeks of de-identified data from patients cared for by
      multiple provider groups in routine community practice for feasibility and
      functionality. Patients included were those in the care of a provider purchasing
      the EpxMedTracking tool from Epharmix and were enrolled from a clinic by their
      providers. The primary outcomes assessed were the rate of engagement with the
      system, reasons for missing doses, and self-reported medication adherence.
      RESULTS: Of the 25 patients studied over the 11 weeks, 3 never responded and
      subsequently opted out or were deleted by their provider. No other patients opted
      out or were deleted during the study period. Across the 11 weeks of the study
      period, the overall weekly engagement rate was 85.9%. There were 109 total
      reported missed doses including "I forgot" at 33 events (30.3%), "I felt better"
      at 29 events (26.6%), "out of meds" at 20 events (18.4%), "I felt sick" at 19
      events (17.4%), and "other" at 3 events (2.8%). We also noted an increase in self
      reported medication adherence in patients using the EpxMedTracking system.
      CONCLUSIONS: EpxMedTracking is an effective tool for tracking self-reported
      medication adherence over time. It uniquely identifies actionable reasons for
      missing doses for subsequent provider intervention in real time based on patient
      feedback. Patients enrolled on EpxMedTracking also self-report higher rates of
      medication adherence over time while on the system.

PMID- 28506955
TI  - Text Messaging and Mobile Phone Apps as Interventions to Improve Adherence in
      Adolescents With Chronic Health Conditions: A Systematic Review.
AB  - BACKGROUND: The number of adolescents with chronic health conditions (CHCs)
      continues to increase. Medication nonadherence is a global challenge among
      adolescents across chronic conditions and is associated with poor health
      outcomes. While there has been growing interest in the use of mHealth technology
      to improve medication adherence among adolescents with CHCs, particularly text
      messaging and mobile phone apps, there has been no prior systematic review of
      their efficacy. OBJECTIVE: The purpose of this review was to systematically
      evaluate the most recent evidence for the efficacy of text messaging and mobile
      phone apps as interventions to promote medication adherence among adolescents
      with CHCs. METHODS: PubMed, Embase, CENTRAL, PsycINFO, Web of Science, Google
      Scholar, and additional databases were searched from 1995 until November 2015. An
      additional hand search of related themes in the Journal of Medical Internet
      Research was also conducted. The Preferred Reporting Results of Systematic
      Reviews and Meta-Analyses guidelines were followed. Two reviewers independently
      screened titles/abstracts, assessed full-text articles, extracted data from
      included articles, and assessed their quality using Grades of Recommendation,
      Assessment, Development, and Evaluation criteria. Included studies were described
      in original research articles that targeted adherence in adolescents with CHCs
      (12-24 years-old). RESULTS: Of the 1423 records examined, 15 met predefined
      criteria: text messaging (n=12) and mobile phone apps (n=3). Most studies were
      performed in the United States (11/15, 73%), were randomized-controlled trials
      (8/15, 53%), had a sample size <50 (11/15, 73%), and included adherence self
      report and/or biomarkers (9/15, 60%). Only four studies were designed based on a
      theoretical framework. Approaches for text messaging and mobile phone app
      interventions varied across studies. Seven articles (7/15, 47%) reported
      significant improvement in adherence with moderate to large standardized mean
      differences. Most of the included studies were of low or moderate quality.
      Studies varied in sample size, methods of adherence assessment, and definition of
      adherence, which prohibited performing a meta-analysis. CONCLUSIONS: The use of
      text messaging and mobile phone app interventions to improve medication adherence
      among adolescents with CHCs has shown promising feasibility and acceptability,
      and there is modest evidence to support the efficacy of these interventions.
      Further evaluation of short- and long-term efficacy and cost-effectiveness of
      these interventions is warranted given the early and evolving state of the
      science.

PMID- 28506956
TI  - Web-Based Cognitive Behavior Therapy for Depression in People With Diabetes
      Mellitus: A Randomized Controlled Trial.
AB  - BACKGROUND: Depression is twice as common in diabetes mellitus (DM) as the
      general population and is associated with adverse health outcomes, but access to
      evidence-based therapies such as cognitive behavioral therapy (CBT) is limited in
      routine diabetes care. Past research has shown that generic Internet-based
      cognitive behavioral therapy (iCBT) is an effective treatment for depression in
      the general population, but it has never been evaluated in people with comorbid
      depression and DM. OBJECTIVE: The aim of our study was to examine the efficacy of
      a generic 6-lesson iCBT delivered over 10 weeks in people with major depressive
      disorder (MDD) and DM. METHODS: Participants with comorbid MDD and DM (type 1 or
      2) were recruited online and randomized to an iCBT program with therapist support
      provided by phone and email (n=42) or a treatment as usual (TAU, n=49) control
      group. Outcomes were assessed through Web-based self-report questionnaires and
      the trial was Web-based with no face-to-face components. Primary outcomes were
      self-reported depression (patient health questionnaire-9, PHQ-9), diabetes
      related distress (problem areas in diabetes, PAID), and self-reported glycemic
      control (hemoglobin A1c, HbA1c). Secondary outcomes were general distress
      (Kessler 10-item psychological distress scale, K-10) and disability (short form
      12-item, SF-12), generalized anxiety (generalized anxiety disorder 7-item, GAD
      7), and somatization (PHQ-15). The iCBT group was assessed at 3 months. RESULTS:
      A total of 27 participants (66%; 27/41) completed the iCBT program. Analyses
      indicated between-group superiority of iCBT over TAU at posttreatment on PHQ-9
      (g=0.78), PAID (g=0.80), K-10 (g=1.06), GAD-7 (g=0.72), and SF-12 mental well
      being scores (g=0.66), but no significant differences in self-reported HbA1c
      levels (g=0.14), SF-12 physical well-being, or PHQ-15 scores (g=0.03-0.21). Gains
      were maintained at 3-month follow-up in the iCBT group, and the 87% (27/31) of
      iCBT participants who were interviewed no longer met criteria for MDD. Clinically
      significant change following iCBT on PHQ-9 scores was 51% (21/41) versus 18%
      (9/49) in TAU. CONCLUSIONS: iCBT for depression is an efficacious, accessible
      treatment option for people with diabetes. Future studies should explore whether
      tailoring of iCBT programs improves acceptability and adherence, and evaluate the
      long-term outcomes following iCBT. TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry (ACTRN): 12613001198718;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365208&isReview=
      rue (Archived by WebCite at http://www.webcitation.org/6qCR8Fi9V).

PMID- 28506957
TI  - Computer Administered Safety Planning for Individuals at Risk for Suicide:
      Development and Usability Testing.
AB  - BACKGROUND: Safety planning is a brief intervention that has become an accepted
      practice in many clinical settings to help prevent suicide. Even though it is
      quick compared to other approaches, it frequently requires 20 min or more to
      complete, which can impede adoption. A self-administered, Web-based safety
      planning application could potentially reduce clinician time, help promote
      standardization and quality, and provide enhanced ability to share the created
      plan. OBJECTIVE: The aim of this study was to design, build, and test the
      usability of a Web-based, self-administered safety planning application. METHODS:
      We employed a user-centered software design strategy led by a multidisciplinary
      team. The application was tested for usability with a target sample of suicidal
      patients. Detailed observations, structured usability ratings, and Think Aloud
      procedures were used. Suicidal ideation intensity and perceived ability to cope
      were assessed pre-post engagement with the Web application. RESULTS: A total of
      30 participants were enrolled. Usability ratings were generally strong, and all
      patients successfully built a safety plan. However, the completeness of the
      safety plan varied. The mean number of steps completed was 5.5 (SD 0.9) out of 6,
      with 90% (27/30) of participants completing at least 5 steps and 67% (20/30)
      completing all 6 steps. Some safety planning steps were viewed as inapplicable to
      some individuals. Some confusion in instructions led to modifications to improve
      understandability of each step. Ratings of suicide intensity after completion of
      the application were significantly lower than preratings, pre: mean 5.11 (SD 2.9)
      versus post: mean 4.46 (SD 3.0), t27=2.49, P=.02. Ratings of ability to cope with
      suicidal thoughts after completion of the application were higher than
      preratings, with the difference approaching statistical significance, pre: mean
      5.93 (SD 2.9), post: mean 6.64 (SD 2.4), t27=-2.03, P=.05. CONCLUSIONS: We have
      taken the first step toward identifying the components needed to maximize
      usability of a self-administered, Web-based safety planning application. Results
      support initial consideration of the application as an adjunct to clinical
      contact. This allows for the clinician or other personnel to provide
      clarification, when needed, to help the patient build the plan, and to help
      review and revise the draft.

PMID- 28506958
TI  - Enhancing Comparative Effectiveness Research With Automated Pediatric Pneumonia
      Detection in a Multi-Institutional Clinical Repository: A PHIS+ Pilot Study.
AB  - BACKGROUND: Community-acquired pneumonia is a leading cause of pediatric
      morbidity. Administrative data are often used to conduct comparative
      effectiveness research (CER) with sufficient sample sizes to enhance detection of
      important outcomes. However, such studies are prone to misclassification errors
      because of the variable accuracy of discharge diagnosis codes. OBJECTIVE: The aim
      of this study was to develop an automated, scalable, and accurate method to
      determine the presence or absence of pneumonia in children using chest imaging
      reports. METHODS: The multi-institutional PHIS+ clinical repository was developed
      to support pediatric CER by expanding an administrative database of children's
      hospitals with detailed clinical data. To develop a scalable approach to find
      patients with bacterial pneumonia more accurately, we developed a Natural
      Language Processing (NLP) application to extract relevant information from chest
      diagnostic imaging reports. Domain experts established a reference standard by
      manually annotating 282 reports to train and then test the NLP application.
      Findings of pleural effusion, pulmonary infiltrate, and pneumonia were
      automatically extracted from the reports and then used to automatically classify
      whether a report was consistent with bacterial pneumonia. RESULTS: Compared with
      the annotated diagnostic imaging reports reference standard, the most accurate
      implementation of machine learning algorithms in our NLP application allowed
      extracting relevant findings with a sensitivity of .939 and a positive predictive
      value of .925. It allowed classifying reports with a sensitivity of .71, a
      positive predictive value of .86, and a specificity of .962. When compared with
      each of the domain experts manually annotating these reports, the NLP application
      allowed for significantly higher sensitivity (.71 vs .527) and similar positive
      predictive value and specificity . CONCLUSIONS: NLP-based pneumonia information
      extraction of pediatric diagnostic imaging reports performed better than domain
      experts in this pilot study. NLP is an efficient method to extract information
      from a large collection of imaging reports to facilitate CER.

PMID- 28506959
TI  - Health-Related Internet Use in People With Cancer: Results From a Cross-Sectional
      Study in Two Outpatient Clinics in Sweden.
AB  - BACKGROUND: The access to various forms of support during the disease trajectory
      is crucial for people with cancer. The provision and use of Internet health
      services is increasing, and it is important to further investigate the
      preferences and demographical characteristics of its users. Investigating the
      uptake and perceived value of Internet health services is a prerequisite to be
      able to meet the needs in the targeted group. OBJECTIVE: The objective of this
      study was to investigate health-related Internet use among people with cancer.
      METHODS: The health online support questionnaire (HOSQ), examining the incentives
      for health-related Internet support use, was administered in two Swedish
      outpatient hospital clinics. Of the 350 copies of the questionnaire handed out,
      285 (81.4%) were returned, answered by persons with cancer who had completed
      treatment or were under active surveillance or another medical treatment.
      RESULTS: A total of 215 (76.2%, 215/282) participants reported Internet use since
      being diagnosed with cancer. Internet-users were younger (P<.001), more likely to
      have a partner (P=.03), and had a higher level of education than nonusers
      (P<.001). The most common health-related activity on the Internet was searching
      for information (77.2%, 166/215), and users searched significantly more
      immediately after diagnosis compared with later on (P<.001). Use of My Healthcare
      Contacts was considered the most valuable Internet activity. Having a university
      degree (P ?.001) and being younger in age (P=.01) were associated with a
      significantly higher frequency of health- related Internet use. CONCLUSIONS:
      People with cancer turn to the Internet for informational support that enables
      them to influence their care and to stay in touch with friends and relatives.
      Demographical differences regarding the uptake of Web-based support remains. This
      indicates a need for research on how to bridge this digital gap. By learning more
      about the use of health-related support on the Web among people with cancer,
      adequate support can be offered and potential strain reduced.

PMID- 28506961
TI  - Gene Team in Blood Pressure Genetics.

PMID- 28506960
TI  - Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the
      Renin-Angiotensin-Aldosterone System and Blood Pressure.
AB  - BACKGROUND: Renin-angiotensin-aldosterone system genes have been inconsistently
      associated with blood pressure, possibly because of unrecognized influences of
      sex-dependent genetic effects or gene-gene interactions (epistasis). METHODS AND
      RESULTS: We tested association of systolic blood pressure with single-nucleotide
      polymorphisms (SNPs) at renin (REN), angiotensinogen (AGT), angiotensin
      converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and aldosterone
      synthase (CYP11B2), including sex-SNP or SNP-SNP interactions. Eighty-eight
      tagSNPs were tested in 2872 white individuals in 809 pedigrees from the Victorian
      Family Heart Study using variance components models. Three SNPs (rs8075924 and
      rs4277404 at ACE and rs12721297 at AGTR1) were individually associated with lower
      systolic blood pressure with significant (P<0.00076) effect sizes ~1.7 to 2.5 mm
      Hg. Sex-specific associations were seen for 3 SNPs in men (rs2468523 and
      rs2478544 at AGT and rs11658531 at ACE) and 1 SNP in women (rs12451328 at ACE).
      SNP-SNP interaction was suggested (P<0.005) for 14 SNP pairs, none of which had
      shown individual association with systolic blood pressure. Four SNP pairs were at
      the same gene (2 for REN, 1 for AGT, and 1 for AGTR1). The SNP rs3097 at CYP11B2
      was represented in 5 separate pairs. CONCLUSIONS: SNPs at key renin-angiotensin
      aldosterone system genes associate with systolic blood pressure individually in
      both sexes, individually in one sex only and only when combined with another SNP.
      Analyses that incorporate sex-dependent and epistatic effects could reconcile
      past inconsistencies and account for some of the missing heritability of blood
      pressure and are generally relevant to SNP association studies for any phenotype.

PMID- 28506963
TI  - Aspirin and Pancreatic Cancer-Response.

PMID- 28506964
TI  - Population-Based Precision Cancer Screening-Letter.

PMID- 28506962
TI  - Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails
      Markers of beta-Cell Dedifferentiation in db/db Mice.
AB  - beta-Cell failure is a hallmark of type 2 diabetes. Among several cellular
      biological mechanisms of cellular dysfunction, we and others have recently
      proposed that dedifferentiation of beta-cells can explain the slowly progressive
      onset and partial reversibility of beta-cell failure. Accordingly, we provided
      evidence of such processes in humans and experimental animal models of insulin
      resistant diabetes. In this study, we asked whether beta-cell dedifferentiation
      can be prevented with diet or pharmacological treatment of diabetes. db/db mice,
      a widely used model of insulin-resistant diabetes and obesity, were either pair
      fed or treated with the Sglt inhibitor phloridzin, the insulin-sensitizer
      rosiglitazone, or insulin. All treatments were equally efficacious in reducing
      plasma glucose levels. Pair feeding and phloridzin also resulted in significant
      weight loss. However, pair feeding among the four treatments resulted in a
      reduction of beta-cell dedifferentiation, as assessed by Foxo1 and Aldh1a3
      immunohistochemistry. The effect of diet to partly restore beta-cell function is
      consistent with data in human diabetes and provides another potential mechanism
      by which lifestyle changes act as an effective intervention against diabetes
      progression.

PMID- 28506966
TI  - Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer
      Letter.

PMID- 28506967
TI  - Aspirin and Pancreatic Cancer-Letter.

PMID- 28506965
TI  - Explaining the Obesity Paradox: The Association between Body Composition and
      Colorectal Cancer Survival (C-SCANS Study).
AB  - Background: Body composition may partially explain the U-shaped association
      between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and
      adiposity at colorectal cancer diagnosis and survival were examined in a
      retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and
      restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%)
      patients. Sarcopenia was defined using optimal stratification and sex- and BMI
      specific cut points. High adiposity was defined as the highest tertile of sex
      specific total adipose tissue (TAT). Primary outcomes were overall mortality and
      colorectal cancer-specific mortality (CRCsM).Results: Slightly over 42% patients
      were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including
      433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95%
      confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those
      who were not sarcopenic. Females with both low muscle and high adiposity had a
      64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females
      with adequate muscle and lower adiposity. The lowest risk of overall mortality
      was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with
      the greatest number of patients (58.6%) who were not at increased risk of overall
      mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is
      prevalent among patients with non-metastatic colorectal cancer, and should, along
      with adiposity be a standard oncological marker.Impact: Our findings suggest a
      biologic explanation for the obesity paradox in colorectal cancer and refute the
      notion that the association between overweight and lower mortality is due solely
      to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. (c)2017
      AACR.

PMID- 28506968
TI  - The Obesity Paradox in Cancer-Moving beyond BMI-Response.

PMID- 28506969
TI  - The Obesity Paradox and Cancer-Letter.

PMID- 28506970
TI  - Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer
      Response.

PMID- 28506972
TI  - Career and research outcomes of the physician-scientist training program at the
      University of Calgary: a retrospective cohort study.
AB  - BACKGROUND: Physician-scientists are integral to medical research, with medical
      programs throughout Canada invested in training hybrid physician-scientists. Few
      data exist as to whether these programs are generating the diversity, gender
      equity and numbers of trainees essential for the future of medical research and
      teaching. We aimed to identify factors that contribute to research productivity,
      diversity and retention of individuals as physician-scientists. METHODS: We
      completed a retrospective cohort study, for the period 1973 to 2015, of the
      University of Calgary Leaders in Medicine Program in Calgary, Alberta.
      Participants were coregistered in graduate (master's or PhD) and medical degree
      programs. Primary outcomes included number of publications and the eventual
      career paths of graduates, with individuals characterized as physicians or
      physician-scientists on the basis of these metrics. RESULTS: Of the 307
      individuals who were coregistered in or had completed a joint graduate and
      medical degree, 125 (40.7%) were PhD students/graduates, and 182 (59.3%) were
      master's trainees/graduates. While in the joint program, male PhD students
      consistently published more frequently than female PhD students. There was no
      significant difference in publication records between male and female master's
      students. Of the 172 individuals who were 5 years or more beyond graduation, 47
      (27.3%) were classified as physician-scientists; these individuals consisted of
      28 (40.6%) of the 69 PhD graduates and 19 (18.4%) of the 103 master's graduates.
      INTERPRETATION: Overall, our study shows that graduates receiving both clinical
      and research training, through master's or PhD programs, continue to be involved
      in research in their subsequent careers.

PMID- 28506974
TI  - Assessment of reimbursement in a community hospital-based pharmacist-managed
      outpatient transition clinic.
AB  - PURPOSE: The assessment of reimbursement for and time spent on patient visits in
      a newly implemented, outpatient pharmacist-managed transition clinic (TC) was
      studied. METHODS: A retrospective chart review was conducted on clinic visits
      that occurred during January 1 to December 31, 2015. Patients who had at least
      one TC visit during the study period were included. Any visit with no response
      from insurance by March 31, 2016, was excluded. Services provided by the TC were
      billed using a facility fee billing model. The following data were collected:
      number of visits, time length of individual visits, billed amount, level of
      service, type of insurance, and amount reimbursed (from primary insurance,
      secondary insurance, and total amount). Data were analyzed using descriptive
      statistics. RESULTS: One hundred eight patients were eligible for inclusion in
      the study, with a total of 306 eligible visits. Each patient had a mean of 2.82
      visits. The mean +/- S.D. time spent per visit was 55 minutes. Visits were billed
      at level 2 (2%), level 3 (36%), and level 4 (62%). Two hundred seventy-two visits
      (89%) were partially or completely reimbursed by insurance, whereas 34 visits
      (11%) provided no reimbursement. The mean +/- S.D. reimbursement was $99 +/-
      $51.88 per visit. CONCLUSION: A pharmacist-managed TC service based in a
      community hospital achieved a positive return on investment through insurer
      reimbursement over a 12-month period.

PMID- 28506975
TI  - National survey of comprehensive pharmacy services provided in cancer clinical
      trials.
AB  - PURPOSE: Pharmacy services provided in clinical trials at National Cancer
      Institute (NCI)-designated centers were assessed. METHODS: This was a cross
      sectional survey of 61 NCI-designated cancer centers. Directors of pharmacy were
      contacted and data were collected electronically via Qualtrics over 2 months.
      Trial participants were asked to estimate the frequency that their sites
      performed 26 services and the perceived importance of these services. Services
      were examined with respect to the difference between their reported performance
      and their reported importance. Eight of the 26 services showed a difference of at
      least 40% between the proportion of respondents performing the activities "often"
      or "almost always" and the proportion considering them "important" or "very
      important." Demographic information was collected, as well as perceived barriers.
      RESULTS: Survey response rate was 59% (36 out of 61). The majority of services
      for clinical trials (19 out of 26) were viewed as important for pharmacists to
      perform; however, less than half (10 out of 26) were performed more than 50% of
      the time. Eight services had a gap of more than 40% when comparing the importance
      versus extent of implementation. Some of the largest gaps were reported in
      investigator-initiated trials development, medication reconciliation, therapeutic
      drug monitoring, and oral chemotherapy adherence assessment. Future studies can
      assist with cost justification by demonstrating the regulatory, safety, and
      financial benefits of pharmacist involvement in cancer trials. CONCLUSION: A
      survey of pharmacy directors at cancer centers revealed gaps between what
      respondents considered important pharmacist services in the provision of cancer
      clinical trials and the actual performance of those services in their
      institution.

PMID- 28506976
TI  - Implementation of postdischarge follow-up telephone calls at a comprehensive
      cancer center.
AB  - PURPOSE: The development and implementation of a pharmacy-driven, postdischarge
      follow-up telephone call program to assess medication adherence, provide
      education, and address medication-related concerns are discussed. SUMMARY: Many
      readmissions are avoidable through effective discharge planning and patient
      follow-up after hospitalization. However, there is limited information on how to
      effectuate this process. To address this barrier, a team consisting of a clinical
      pharmacy specialist, a clinical pharmacy manager, a postgraduate year 1 pharmacy
      resident, and an education specialist at The University of Texas MD Anderson
      Cancer Center collaborated to create a postdischarge telephone call program
      within a transitions-of-care (TOC) pilot program. Various education and training
      materials were created to ensure trainees were competent. As of February 2016, 23
      outpatient pharmacists and students have completed training, earning a median
      pretest and posttest score of 6 and 9, respectively, out of 10. There have been
      206 calls completed; 150 patients (73%) were successfully reached, and 20
      patients (9%) declined the telephone call. Medication adherence assessed during
      the telephone follow-up identified that 134 patients (89%) received their new
      medications within 72 hours, and 87 patients (58%) were recognized as having one
      or more discrepancies. CONCLUSION: Developing a TOC program similar to this pilot
      program requires several resources including time, collaboration, and support
      from the management team. Pharmacy is well positioned to complete an accurate
      medication review and conduct postdischarge telephone calls to address medication
      related issues. By providing these services, patients will receive continuity of
      care and positively impact emergency room visitation rates and hospital
      readmission rates.

PMID- 28506971
TI  - Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and
      Risk for Coronary Heart Disease.
AB  - RATIONALE: Therapies that inhibit CETP (cholesteryl ester transfer protein) have
      failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human
      DNA sequence variants that truncate the CETP gene may provide insight into the
      efficacy of CETP inhibition. OBJECTIVE: To test whether protein-truncating
      variants (PTVs) at the CETP gene were associated with plasma lipid levels and
      CHD. METHODS AND RESULTS: We sequenced the exons of the CETP gene in 58 469
      participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free
      controls). We defined PTV as those that lead to a premature stop, disrupt
      canonical splice sites, or lead to insertions/deletions that shift frame. We also
      genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control
      studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of
      CETP PTV carrier status with both plasma lipids and CHD. Among 58 469
      participants with CETP gene-sequencing data available, average age was 51.5 years
      and 43% were women; 1 in 975 participants carried a PTV at the CETP gene.
      Compared with noncarriers, carriers of PTV at CETP had higher high-density
      lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27;
      P<1.0*10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95%
      confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95%
      confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was
      associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence
      interval, 0.54-0.90; P=5.1*10-3). CONCLUSIONS: Compared with noncarriers,
      carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol,
      lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk
      for CHD.

PMID- 28506977
TI  - Development of a medication review service for patients with enteral tubes in a
      community teaching hospital.
AB  - PURPOSE: The results of a study to develop a hospital-wide medication review
      service for patients with enteral tubes to improve patient safety are presented.
      SUMMARY: Inappropriate enteral administration of medications can result in
      occluded tubes, altered clinical response, and an increase in adverse effects. At
      Saint Barnabas Medical Center, a 600-bed community teaching hospital located in
      Livingston, New Jersey, a medication review service for patients with an enteral
      tube was developed. A phased approach was used. In phase 1, a retrospective chart
      review revealed that 43% of our patients with enteral tubes received at least one
      medication that should not be crushed. In phase 2, we identified formulary
      medications that should not be crushed based on guidance from the Institute for
      Safe Medication Practices. We added a "do not crush" warning to the identified
      medications in our electronic medication administration record and automated
      medication dispensing system. In phase 3, we created an automatic substitution
      list of medications. Phase 4 involved the development of the program in our
      health information technology platform. An electronic task list alerted
      pharmacists about patients with enteral tubes who required medication review and
      potential medication substitutions, as well as patients with newly removed
      enteral tubes who can be placed back on their original medications. In phase 5,
      we provided education to prescribers, nurses, and pharmacists. CONCLUSION: A
      hospital-wide medication review service for patients with enteral tubes at our
      community teaching medical center was developed.

PMID- 28506916
TI  - 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and
      surgical ablation of atrial fibrillation.

PMID- 28506978
TI  - Addition of Blood Pressure and Weight Transmissions to Standard Remote Monitoring
      of Implantable Defibrillators and its Association with Mortality and
      Rehospitalization.
AB  - BACKGROUND: Among patients with implantable defibrillators (ICD), use of remote
      patient monitoring (RPM) is associated with lower risk of death and
      rehospitalization. Standard ICD RPM can be supplemented with weight and blood
      pressure data. It is not known whether standard RPM plus routine weight and blood
      pressure transmission (RPM+) is associated with better outcomes. METHODS AND
      RESULTS: RPM+ patients (n=4106) were compared with patients who only transmitted
      standard ICD RPM data (n=14 183). Logistic regression models identified patient,
      physician, and hospital characteristics associated with RPM+ utilization.
      Mortality and rehospitalization were examined using landmark analyses at 180 days
      after ICD implant in Medicare fee-for-service patients. In these analyses, we
      examined the independent association between RPM+ utilization and times to events
      up to 3 years after device implantation with Cox regression models. We further
      examined whether the association between RPM+ and outcomes varied by frequency or
      type of transmissions. Determinants of RPM+ utilization included impaired
      ejection fraction, cardiac resynchronization therapy, and institutional practice.
      The risk of mortality of RPM+ patients was similar to standard ICD RPM patients
      (hazard ratio, 1.06; 95% confidence interval, 0.94-1.19; P=0.34). RPM+ patients
      also had similar risks of all-cause hospitalization (subdistribution hazard
      ratio, 1.03; 95% confidence interval, 0.94-1.14; P=0.52), cardiovascular
      hospitalization (subdistribution hazard ratio, 0.92; 95% confidence interval,
      0.83-1.02; P=0.15), or heart failure hospitalizations (subdistribution hazard
      ratio, 0.90; 95% confidence interval, 0.78-1.05; P=0.18). RPM+ transmission
      frequency was not associated with outcomes. CONCLUSIONS: In patients using
      standard ICD RPM, the added transmission of weight and blood pressure data was
      not associated with improved outcomes.

PMID- 28506979
TI  - Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and
      Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results
      From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy
      International Trial).
AB  - BACKGROUND: Ezetimibe, when added to simvastatin therapy, reduces cardiovascular
      events after recent acute coronary syndrome. However, the impact of ezetimibe on
      cardiovascular-related hospitalizations and associated costs is unknown. METHODS
      AND RESULTS: We used patient-level data from the IMPROVE-IT (Improved Reduction
      of Outcomes: Vytorin Efficacy International Trial) to examine the impact of
      simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related
      hospitalizations and related costs (excluding drug costs) over 7 years follow-up.
      Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular
      hospitalizations. Hospital costs were estimated using Medicare reimbursement
      rates for 2013. Associated physician costs were estimated as a percentage of
      hospital costs. The impact of treatment assignment on hospitalization rates and
      costs was estimated using Poisson and linear regression, respectively. There was
      a significantly lower cardiovascular hospitalization rate with ezetimibe compared
      with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99; P=0.031),
      mainly attributable to fewer hospitalizations for percutaneous coronary
      intervention, angina, and stroke. Consequently, cardiovascular-related
      hospitalization costs over 7 years were $453 per patient lower with ezetimibe
      (95% confidence interval, -$38 to -$869; P=0.030). Although all prespecified
      subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus,
      patients aged >=75 years, and patients at higher predicted risk for recurrent
      ischemic events had even greater cost offsets. CONCLUSIONS: Addition of ezetimibe
      to statin therapy in patients with a recent acute coronary syndrome leads to
      reductions in cardiovascular-related hospitalizations and associated costs, with
      the greatest cost offsets in high-risk patients. These cost reductions may
      completely offset the cost of the drug once ezetimibe becomes generic, and may
      lead to cost savings from the perspective of the healthcare system, if treatment
      with ezetimibe is targeted to high-risk patients. CLINICAL TRIAL REGISTRATION:
      URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878.

PMID- 28506982
TI  - Social Risk Factors and Performance Under Medicare's Value-Based Purchasing
      Programs.

PMID- 28506983
TI  - Riskier Business: Atrial Fibrillation Stroke Prevention in the CHA2DS2-VASc Era.

PMID- 28506984
TI  - Even on a Large Scale, Weight May Not Matter.

PMID- 28506981
TI  - Contemporary Trends in Oral Anticoagulant Prescription in Atrial Fibrillation
      Patients at Low to Moderate Risk of Stroke After Guideline-Recommended Change in
      Use of the CHADS2 to the CHA2DS2-VASc Score for Thromboembolic Risk Assessment:
      Analysis From the National Cardiovascular Data Registry's Outpatient Practice
      Innovation and Clinical Excellence Atrial Fibrillation Registry.
AB  - BACKGROUND: Use of the CHA2DS2-VASc score instead of the CHADS2 score for
      thromboembolic risk stratification and initiation of oral anticoagulation (OAC)
      was recommended in the 2014 American Heart Association/American College of
      Cardiology/Heart Rhythm Society atrial fibrillation (AF) guidelines. We sought to
      define the proportion of patients with AF qualifying for and receiving OAC in
      contemporary practice by applying the CHA2DS2-VASc score to patients with a low
      CHADS2 score. METHODS AND RESULTS: Among patients with AF enrolled in the
      American College of Cardiology National Cardiovascular Data Registry's outpatient
      Practice Innovation and Clinical Excellence registry (2008-2014) CHADS2 score of
      0 or 1, we calculated the impact of adoption of the CHA2DS2-VASc score on the
      proportion of patients with an indication for OAC. We examined trends in
      prescription of OAC overall, direct OAC (dabigatran/rivaroxaban/apixaban), and
      multivariable associations between clinical characteristics and OAC use. Of 346
      068 patients with AF aged 65+/-12 years, 61% were men and 65% were white. In
      total, 24% of those with CHADS2=0 and 81% of those with a CHADS2=1 were
      reclassified as having a definite indication for OAC (CHA2DS2-VASc score >=2).
      OAC use increased from 37% to 48% during the study period, and direct OAC use
      increased from 5% to 30%. Increasing CHA2DS2-VASc score (odds ratio, 2.07; 95%
      confidence interval, 1.97-2.19 for score of 4 versus 0) and rhythm control
      strategy (odds ratio, 1.34; 95% confidence interval, 1.30-1.39) were associated
      with increased OAC use. CONCLUSIONS: Adoption of the CHA2DS2-VASc score
      reclassifies 64.5% of patients with AF with low CHADS2 scores into a class I
      indication for OAC prescription. Overall OAC prescription increased between 2011
      and 2014.

PMID- 28506980
TI  - Sex Differences in Trajectories of Risk After Rehospitalization for Heart
      Failure, Acute Myocardial Infarction, or Pneumonia.
AB  - BACKGROUND: Women have an increased risk of rehospitalization in the immediate
      postdischarge period; however, few studies have determined how readmission risk
      dynamically changes on a day-to-day basis over the full year after
      hospitalization by sex and how these differences compare with the risk for
      mortality. METHODS AND RESULTS: We identified >3 000 000 hospitalizations of
      patients with a principal discharge diagnosis of heart failure, acute myocardial
      infarction, or pneumonia and estimated sex differences in the daily risk of
      rehospitalization/death 1 year after discharge from a population of Medicare fee
      for-service beneficiaries aged 65 years and older. We calculated the (1) time
      required for adjusted rehospitalization/mortality risks to decline 50% from
      maximum values after discharge, (2) time required for the adjusted readmission
      risk to approach plateau periods of minimal day-to-day change, and (3) extent to
      which adjusted risks are greater among recently hospitalized patients versus
      Medicare patients. We identified 1 392 289, 530 771, and 1 125 231
      hospitalizations for heart failure, acute myocardial infarction, and pneumonia,
      respectively. The adjusted daily risk of rehospitalization varied by admitting
      condition (hazard rate ratio for women versus men, 1.10 for acute myocardial
      infarction; hazard rate ratio, 1.04 for heart failure; and hazard rate ratio,
      0.98 for pneumonia). However, for all conditions, the adjusted daily risk of
      death was higher among men versus women (hazard rate ratio women versus with men,
      <1). For both sexes, there was a similar timing of peak daily risk, half daily
      risk, and reaching plateau. CONCLUSIONS: Although the association of sex with
      daily risk of rehospitalization varies across conditions, women are at highest
      risk after discharge for acute myocardial infarction. Future studies should focus
      on understanding the determinants of sex differences in rehospitalization risk
      among conditions.

PMID- 28506985
TI  - Histone acetyltransferase KAT8 is essential for mouse oocyte development by
      regulating reactive oxygen species levels.
AB  - Proper oocyte development is crucial for female fertility and requires timely and
      accurate control of gene expression. K (lysine) acetyltransferase 8 (KAT8), an
      important component of the X chromosome dosage compensation system in Drosophila,
      regulates gene activity by acetylating histone H4 preferentially at lysine 16. To
      explore the function of KAT8 during mouse oocyte development, we crossed
      Kat8flox/flox mice with Gdf9-Cre mice to specifically delete Kat8 in oocytes.
      Oocyte Kat8 deletion resulted in female infertility, with follicle development
      failure in the secondary and preantral follicle stages. RNA-seq analysis revealed
      that Kat8 deficiency in oocytes results in significant downregulation of
      antioxidant genes, with a consequent increase in reactive oxygen species.
      Intraperitoneal injection of the antioxidant N-acetylcysteine rescued defective
      follicle and oocyte development resulting from Kat8 deficiency. Chromatin
      immunoprecipitation assays indicated that KAT8 regulates antioxidant gene
      expression by direct binding to promoter regions. Taken together, our findings
      demonstrate that KAT8 is essential for female fertility by regulating antioxidant
      gene expression and identify KAT8 as the first histone acetyltransferase with an
      essential function in oogenesis.

PMID- 28506986
TI  - SoxNeuro and Shavenbaby act cooperatively to shape denticles in the embryonic
      epidermis of Drosophila.
AB  - During development, extracellular signals are integrated by cells to induce the
      transcriptional circuitry that controls morphogenesis. In the fly epidermis,
      Wingless (Wg)/Wnt signaling directs cells to produce either a distinctly shaped
      denticle or no denticle, resulting in a segmental pattern of denticle belts
      separated by smooth, or 'naked', cuticle. Naked cuticle results from Wg
      repression of shavenbaby (svb), which encodes a transcription factor required for
      denticle construction. We have discovered that although the svb promoter responds
      differentially to altered Wg levels, Svb alone cannot produce the morphological
      diversity of denticles found in wild-type belts. Instead, a second Wg-responsive
      transcription factor, SoxNeuro (SoxN), cooperates with Svb to shape the
      denticles. Co-expressing ectopic SoxN with svb rescued diverse denticle
      morphologies. Conversely, removing SoxN activity eliminated the residual
      denticles found in svb mutant embryos. Furthermore, several known Svb target
      genes are also activated by SoxN, and we have discovered two novel target genes
      of SoxN that are expressed in denticle-producing cells and that are regulated
      independently of Svb. We conclude that proper denticle morphogenesis requires
      transcriptional regulation by both SoxN and Svb.

PMID- 28506987
TI  - Development of the larval lymphatic system in zebrafish.
AB  - The lymphatic vascular system is a hierarchically organized complex network
      essential for tissue fluid homeostasis, immune trafficking and absorption of
      dietary fats in the human body. Despite its importance, the assembly of the
      lymphatic network is still not fully understood. The zebrafish is a powerful
      model organism that enables study of lymphatic vessel development using high
      resolution imaging and sophisticated genetic and experimental manipulation.
      Although several studies have described early lymphatic development in the fish,
      lymphatic development at later stages has not been completely elucidated. In this
      study, we generated a new Tg(mrc1a:egfp)y251 transgenic zebrafish that uses a
      mannose receptor, C type 1 (mrc1a) promoter to drive strong EGFP expression in
      lymphatic vessels at all stages of development and in adult zebrafish. We used
      this line to describe the assembly of the major vessels of the trunk lymphatic
      vascular network, including the later-developing collateral cardinal, spinal,
      superficial lateral and superficial intersegmental lymphatics. Our results show
      that major trunk lymphatic vessels are conserved in the zebrafish, and provide a
      thorough and complete description of trunk lymphatic vessel assembly.

PMID- 28506988
TI  - Dmrt1 induces the male pathway in a turtle species with temperature-dependent sex
      determination.
AB  - The molecular mechanism underlying temperature-dependent sex determination (TSD)
      has been a long-standing mystery; in particular, the thermosensitive genetic
      triggers for gonadal sex differentiation are largely unknown. Here, we have
      characterized a conserved DM domain gene, Dmrt1, in the red-eared slider turtle
      Trachemys scripta (T. scripta), which exhibits TSD. We found that Dmrt1 has a
      temperature-dependent, sexually dimorphic expression pattern, preceding gonadal
      sex differentiation, and is capable of responding rapidly to temperature shifts
      and aromatase inhibitor treatment. Most importantly, loss- and gain-of-function
      analyses provide solid evidence that Dmrt1 is both necessary and sufficient to
      initiate male development in T. scripta Furthermore, the DNA methylation dynamics
      of the Dmrt1 promoter are tightly correlated with temperature and could mediate
      the impact of temperature on sex determination. Collectively, our findings
      demonstrate that Dmrt1 is a candidate master male sex-determining gene in this
      TSD species, consistent with the idea that DM domain genes are conserved during
      the evolution of sex determination mechanisms.

PMID- 28506990
TI  - COUP-TFI mitotically regulates production and migration of dentate granule cells
      and modulates hippocampal Cxcr4 expression.
AB  - Development of the dentate gyrus (DG), the primary gateway for hippocampal
      inputs, spans embryonic and postnatal stages, and involves complex morphogenetic
      events. We have previously identified the nuclear receptor COUP-TFI as a novel
      transcriptional regulator in the postnatal organization and function of the
      hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in
      either granule cell progenitors or granule neurons. Loss of COUP-TFI function in
      progenitors leads to decreased granule cell proliferative activity, precocious
      differentiation and increased apoptosis, resulting in a severe DG growth defect
      in adult mice. COUP-TFI-deficient cells express high levels of the chemokine
      receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of
      differentiated granule cells along their paths. Conversely, high COUP-TFI
      expression levels downregulate Cxcr4 expression, whereas increased Cxcr4
      expression in wild-type hippocampal cells affects cell migration. Finally, loss
      of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities,
      and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is
      required predominantly in DG progenitors for modulating expression of the Cxcr4
      receptor during granule cell neurogenesis and migration.

PMID- 28506989
TI  - FGF signaling refines Wnt gradients to regulate the patterning of taste papillae.
AB  - The patterning of repeated structures is a major theme in developmental biology,
      and the inter-relationship between spacing and size of such structures is an
      unresolved issue. Fungiform papillae are repeated epithelial structures that
      house taste buds on the anterior tongue. Here, we report that FGF signaling is a
      crucial regulator of fungiform papillae development. We found that mesenchymal
      FGF10 controls the size of the papillary area, while overall patterning remains
      unchanged. Our results show that FGF signaling negatively affects the extent of
      canonical Wnt signaling, which is the main activation pathway during fungiform
      papillae development; however, this effect does not occur at the level of gene
      transcription. Rather, our experimental data, together with computational
      modeling, indicate that FGF10 modulates the range of Wnt effects, likely via
      induction of Sostdc1 expression. We suggest that modification of the reach of Wnt
      signaling could be due to local changes in morphogen diffusion, representing a
      novel mechanism in this tissue context, and we propose that this phenomenon might
      be involved in a broader array of mammalian developmental processes.

PMID- 28506992
TI  - Reduced MAD2 levels dampen the apoptotic response to non-exchange sex chromosomes
      and lead to sperm aneuploidy.
AB  - In meiosis, non-exchange homologous chromosomes are at risk for mis-segregation
      and should be monitored by the spindle assembly checkpoint (SAC) to avoid
      formation of aneuploid gametes. Sex chromosome mis-segregation is particularly
      common and can lead to sterility or to aneuploid offspring (e.g. individuals with
      Turner or Klinefelter syndrome). Despite major implications for health and
      reproduction, modifiers of meiotic SAC robustness and the subsequent apoptotic
      response in male mammals remain obscure. Levels of SAC proteins, e.g. MAD2, are
      crucial for normal checkpoint function in many experimental systems, but
      surprisingly, apparently not in male meiosis, as indicated by the lack of
      chromosome segregation defects reported earlier in Mad2+/- spermatocytes. To
      directly test whether MAD2 levels impact the meiotic response to mis-segregating
      chromosomes, we used Spo11beta-onlymb mice that are prone to non-exchange X-Y
      chromosomes. We show that reduced MAD2 levels attenuate the apoptotic response to
      mis-segregating sex chromosomes and allow the formation of aneuploid sperm. These
      findings demonstrate that SAC protein levels are crucial for the efficient
      elimination of aberrant spermatocytes.

PMID- 28506991
TI  - Sonic hedgehog regulation of Foxf2 promotes cranial neural crest mesenchyme
      proliferation and is disrupted in cleft lip morphogenesis.
AB  - Cleft lip is one of the most common human birth defects, yet our understanding of
      the mechanisms that regulate lip morphogenesis is limited. Here, we show in mice
      that sonic hedgehog (Shh)-induced proliferation of cranial neural crest cell
      (cNCC) mesenchyme is required for upper lip closure. Gene expression profiling
      revealed a subset of Forkhead box (Fox) genes that are regulated by Shh signaling
      during lip morphogenesis. During cleft pathogenesis, reduced proliferation in the
      medial nasal process mesenchyme paralleled the domain of reduced Foxf2 and Gli1
      expression. SHH ligand induction of Foxf2 expression was dependent upon Shh
      pathway effectors in cNCCs, while a functional GLI-binding site was identified
      downstream of Foxf2 Consistent with the cellular mechanism demonstrated for cleft
      lip pathogenesis, we found that either SHH ligand addition or FOXF2
      overexpression is sufficient to induce cNCC proliferation. Finally, analysis of a
      large multi-ethnic human population with cleft lip identified clusters of single
      nucleotide polymorphisms in FOXF2 These data suggest that direct targeting of
      Foxf2 by Shh signaling drives cNCC mesenchyme proliferation during upper lip
      morphogenesis, and that disruption of this sequence results in cleft lip.

PMID- 28506995
TI  - Apical constriction is driven by a pulsatile apical myosin network in
      delaminating Drosophila neuroblasts.
AB  - Cell delamination is a conserved morphogenetic process important for the
      generation of cell diversity and maintenance of tissue homeostasis. Here, we used
      Drosophila embryonic neuroblasts as a model to study the apical constriction
      process during cell delamination. We observe dynamic myosin signals both around
      the cell adherens junctions and underneath the cell apical surface in the
      neuroectoderm. On the cell apical cortex, the nonjunctional myosin forms flows
      and pulses, which are termed medial myosin pulses. Quantitative differences in
      medial myosin pulse intensity and frequency are crucial to distinguish
      delaminating neuroblasts from their neighbors. Inhibition of medial myosin pulses
      blocks delamination. The fate of a neuroblast is set apart from that of its
      neighbors by Notch signaling-mediated lateral inhibition. When we inhibit Notch
      signaling activity in the embryo, we observe that small clusters of cells undergo
      apical constriction and display an abnormal apical myosin pattern. Together,
      these results demonstrate that a contractile actomyosin network across the apical
      cell surface is organized to drive apical constriction in delaminating
      neuroblasts.

PMID- 28506993
TI  - MAPK pathway control of stem cell proliferation and differentiation in the
      embryonic pituitary provides insights into the pathogenesis of papillary
      craniopharyngioma.
AB  - Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and
      disease of numerous organs, its role during pituitary development and
      tumourigenesis remains largely unknown. Here, we show that the over-activation of
      the MAPK pathway, through conditional expression of the gain-of-function alleles
      BrafV600E and KrasG12D in the developing mouse pituitary, results in severe
      hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell
      lineage commitment and terminal differentiation are disrupted, leading to a
      significant reduction in numbers of most of the hormone-producing cells before
      birth, with the exception of corticotrophs. Of note, Sox2+ stem cells and
      clonogenic potential are drastically increased in the mutant pituitaries.
      Finally, we reveal that papillary craniopharyngioma (PCP), a benign human
      pituitary tumour harbouring BRAF p.V600E also contains Sox2+ cells with sustained
      proliferative capacity and disrupted pituitary differentiation. Together, our
      data demonstrate a crucial function of the MAPK pathway in controlling the
      balance between proliferation and differentiation of Sox2+ cells and suggest that
      persistent proliferative capacity of Sox2+ cells may underlie the pathogenesis of
      PCP.

PMID- 28506994
TI  - Gain-of-function mutations in Aqp3a influence zebrafish pigment pattern formation
      through the tissue environment.
AB  - The development of the pigmentation pattern in zebrafish is a tightly regulated
      process that depends on both the self-organizing properties of pigment cells and
      extrinsic cues from other tissues. Many of the known mutations that alter the
      pattern act cell-autonomously in pigment cells, and our knowledge about external
      regulators is limited. Here, we describe novel zebrafish mau mutants, which
      encompass several dominant missense mutations in Aquaporin 3a (Aqp3a) that lead
      to broken stripes and short fins. A loss-of-function aqp3a allele, generated by
      CRISPR-Cas9, has no phenotypic consequences, demonstrating that Aqp3a is
      dispensable for normal development. Strikingly, the pigment cells from dominant
      mau mutants are capable of forming a wild-type pattern when developing in a wild
      type environment, but the surrounding tissues in the mutants influence pigment
      cell behaviour and interfere with the patterning process. The mutated amino acid
      residues in the dominant alleles line the pore surface of Aqp3a and influence
      pore permeability. These results demonstrate an important effect of the tissue
      environment on pigment cell behaviour and, thereby, on pattern formation.

PMID- 28506997
TI  - The phosphatase Pgam5 antagonizes Wnt/beta-Catenin signaling in embryonic
      anterior-posterior axis patterning.
AB  - The scaffold protein Dishevelled is a central intracellular component of Wnt
      signaling pathways. Various kinases have been described that regulate and
      modulate Wnt signaling through phosphorylation of Dishevelled. However, besides
      general protein phosphatases 1 and 2 (PP1 and PP2), no specific protein
      phosphatases have been identified. Here, we report on the identification and
      functional characterization of the protein phosphatase Pgam5 in vitro and in vivo
      in Xenopus Pgam5 is a novel antagonist of Wnt/beta-Catenin signaling in human
      cells and Xenopus embryogenesis. In early development, Pgam5 is essential for
      head formation, and for establishing and maintaining the Wnt/beta-Catenin
      signaling gradient that patterns the anterior-posterior body axis. Inhibition of
      Wnt/beta-Catenin signaling and developmental function depend on Pgam5 phosphatase
      activity. We show that Pgam5 interacts with Dishevelled2 and that Dishevelled2 is
      a substrate of Pgam5. Pgam5 mediates a marked decrease in Dishevelled2
      phosphorylation in the cytoplasm and in the nucleus, as well as decreased
      interaction between Dishevelled2, Tcf1 and beta-Catenin, indicating that Pgam5
      regulates Dishevelled function upstream and downstream of beta-Catenin
      stabilization.

PMID- 28506996
TI  - RET-mediated glial cell line-derived neurotrophic factor signaling inhibits mouse
      prostate development.
AB  - In humans and rodents, the prostate gland develops from the embryonic urogenital
      sinus (UGS). The androgen receptor (AR) is thought to control the expression of
      morphogenetic genes in inductive UGS mesenchyme, which promotes proliferation and
      cytodifferentiation of the prostatic epithelium. However, the nature of the AR
      regulated morphogenetic genes and the mechanisms whereby AR controls prostate
      development are not understood. Glial cell line-derived neurotrophic factor
      (GDNF) binds GDNF family receptor alpha1 (GFRalpha1) and signals through
      activation of RET tyrosine kinase. Gene disruption studies in mice have revealed
      essential roles for GDNF signaling in development; however, its role in prostate
      development is unexplored. Here, we establish novel roles of GDNF signaling in
      mouse prostate development. Using an organ culture system for prostate
      development and Ret mutant mice, we demonstrate that RET-mediated GDNF signaling
      in UGS increases proliferation of mesenchyme cells and suppresses androgen
      induced proliferation and differentiation of prostate epithelial cells,
      inhibiting prostate development. We also identify Ar as a GDNF-repressed gene and
      Gdnf and Gfralpha1 as androgen-repressed genes in UGS, thus establishing
      reciprocal regulatory crosstalk between AR and GDNF signaling in prostate
      development.

PMID- 28506998
TI  - Fgf10 and Sox9 are essential for the establishment of distal progenitor cells
      during mouse salivary gland development.
AB  - Salivary glands are formed by branching morphogenesis with epithelial progenitors
      forming a network of ducts and acini (secretory cells). During this process,
      epithelial progenitors specialise into distal (tips of the gland) and proximal
      (the stalk region) identities that produce the acini and higher order ducts,
      respectively. Little is known about the factors that regulate progenitor
      expansion and specialisation in the different parts of the gland. Here, we show
      that Sox9 is involved in establishing the identity of the distal compartment
      before the initiation of branching morphogenesis. Sox9 is expressed throughout
      the gland at the initiation stage before becoming restricted to the distal
      epithelium from the bud stage and throughout branching morphogenesis. Deletion of
      Sox9 in the epithelium results in loss of the distal epithelial progenitors, a
      reduction in proliferation and a subsequent failure in branching. We demonstrate
      that Sox9 is positively regulated by mesenchymal Fgf10, a process that requires
      active Erk signalling. These results provide new insights into the factors
      required for the expansion of salivary gland epithelial progenitors, which can be
      useful for organ regeneration therapy.

PMID- 28506999
TI  - Btbd7 is essential for region-specific epithelial cell dynamics and branching
      morphogenesis in vivo.
AB  - Branching morphogenesis of developing organs requires coordinated but poorly
      understood changes in epithelial cell-cell adhesion and cell motility. We report
      that Btbd7 is a crucial regulator of branching morphogenesis in vivo. Btbd7
      levels are elevated in peripheral cells of branching epithelial end buds, where
      it enhances cell motility and cell-cell adhesion dynamics. Genetic ablation of
      Btbd7 in mice disrupts branching morphogenesis of salivary gland, lung and
      kidney. Btbd7 knockout results in more tightly packed outer bud cells, which
      display stronger E-cadherin localization, reduced cell motility and decreased
      dynamics of transient cell separations associated with cleft formation; inner bud
      cells remain unaffected. Mechanistic analyses using in vitro MDCK cells to mimic
      outer bud cell behavior establish that Btbd7 promotes loss of E-cadherin from
      cell-cell adhesions with enhanced migration and transient cell separation. Btbd7
      can enhance E-cadherin ubiquitination, internalization, and degradation in MDCK
      and peripheral bud cells for regulating cell dynamics. These studies show how a
      specific regulatory molecule, Btbd7, can function at a local region of developing
      organs to regulate dynamics of cell adhesion and motility during epithelial
      branching morphogenesis.

PMID- 28507000
TI  - The cell wall-localized atypical beta-1,3 glucanase ZERZAUST controls tissue
      morphogenesis in Arabidopsis thaliana.
AB  - Orchestration of cellular behavior in plant organogenesis requires integration of
      intercellular communication and cell wall dynamics. The underlying signaling
      mechanisms are poorly understood. Tissue morphogenesis in Arabidopsis depends on
      the receptor-like kinase STRUBBELIG. Mutations in ZERZAUST were previously shown
      to result in a strubbelig-like mutant phenotype. Here, we report on the molecular
      identification and functional characterization of ZERZAUST We show that ZERZAUST
      encodes a putative GPI-anchored beta-1,3 glucanase suggested to degrade the cell
      wall polymer callose. However, a combination of in vitro, cell biological and
      genetic experiments indicate that ZERZAUST is not involved in the regulation of
      callose accumulation. Nonetheless, Fourier-transformed infrared-spectroscopy
      revealed that zerzaust mutants show defects in cell wall composition.
      Furthermore, the results indicate that ZERZAUST represents a mobile apoplastic
      protein, and that its carbohydrate-binding module family 43 domain is required
      for proper subcellular localization and function whereas its GPI anchor is
      dispensable. Our collective data reveal that the atypical beta-1,3 glucanase
      ZERZAUST acts in a non-cell-autonomous manner and is required for cell wall
      organization during tissue morphogenesis.

PMID- 28507003
TI  - Surgeon is struck off after three "never events".

PMID- 28507001
TI  - p38 MAPK as an essential regulator of dorsal-ventral axis specification and
      skeletogenesis during sea urchin development: a re-evaluation.
AB  - Dorsal-ventral axis formation in the sea urchin embryo relies on the asymmetrical
      expression of the TGFbeta Nodal. The p38-MAPK pathway has been proposed to be
      essential for dorsal-ventral axis formation by acting upstream of nodal
      expression. Here, we report that, in contrast to previous studies that used
      pharmacological inhibitors of p38, manipulating the activity of p38 by genetic
      means has no obvious impact on morphogenesis. Instead, we discovered that p38
      inhibitors strongly disrupt specification of all germ layers by blocking
      signalling from the Nodal receptor and by interfering with the ERK pathway.
      Strikingly, while expression of a mutant p38 that is resistant to SB203580 did
      not rescue dorsal-ventral axis formation or skeletogenesis in embryos treated
      with this inhibitor, expression of mutant Nodal receptors that are resistant to
      SB203580 fully restored nodal expression in SB203580-treated embryos. Taken
      together, these results establish that p38 activity is not required for dorsal
      ventral axis formation through nodal expression nor for skeletogenesis. Our
      results prompt a re-evaluation of the conclusions of several recent studies that
      linked p38 activity to dorsal-ventral axis formation and to patterning of the
      skeleton.

PMID- 28507002
TI  - Neuregulin 1 Allosterically Enhances the Antitumor Effects of the Noncompeting
      Anti-HER3 Antibody 9F7-F11 by Increasing Its Binding to HER3.
AB  - Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly
      suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a
      predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized
      that in NRG1-expressing tumors, where the ligand is present before antibody
      treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor
      binding have a higher receptor-neutralizing action than antibodies competing with
      the ligand for binding to HER3. Using time-resolved-fluorescence energy transfer
      (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of
      9F7-F11 (a nonligand-competing anti-HER3 antibody) to HER3 is increased, whereas
      that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6,
      Mab205.10.2, and MOR09825) is decreased. Moreover, 9F7-F11 showed higher efficacy
      than antibodies that compete with the ligand for binding to HER3. Specifically,
      9F7-F11 inhibition of cell proliferation and of HER3/AKT/ERK1/2 phosphorylation
      as well as 9F7-F11-dependent cell-mediated cytotoxicity were higher in cancer
      cells preincubated with recombinant NRG1 compared with cells directly exposed to
      the anti-HER3 antibody. This translated in vivo into enhanced growth inhibition
      of NRG1-expressing BxPC3 pancreatic, A549 lung, and HCC-1806 breast cell tumor
      xenografts in mice treated with 9F7-F11 compared with H4B-121. Conversely, both
      antibodies had similar antitumor effect in NRG1-negative HPAC pancreatic
      carcinoma cells. In conclusion, the allosteric modulator 9F7-F11 shows increased
      anticancer effectiveness in the presence of NRG1 and thus represents a novel
      treatment strategy for NRG1-addicted tumors. Mol Cancer Ther; 16(7); 1312-23.
      (c)2017 AACR.

PMID- 28507005
TI  - Perspective: What Makes It So Difficult to Mitigate Worldwide Anemia Prevalence?
AB  - Anemia can be related to decreased production or increased loss of erythrocytes,
      or both, leading to many underlying and often overlapping causes. A largely
      cereal-based diet with plenty of phytates, polyphenols, and other ligands that
      inhibit intestinal iron absorption predominated in preindustrial Europe and
      predominates in present-day developing countries alike. In both situations, we
      find poor hygienic conditions, which frequently lead to anemia of inflammation.
      The large number of possible causes and their interaction shows why it is so
      difficult to mitigate anemia prevalence. Diagnostic biomarkers are required to
      differentiate the different types of anemia and to treat them appropriately. Some
      of them are well established in adults [e.g., concentrations of serum ferritin,
      soluble transferrin receptor (sTfR), and serum iron or the ratio of sTfR to log
      ferritin]. Others, such as serum hepcidin, hold considerable promise, although
      they are not yet widely used. A particular issue is to establish reference values
      for biomarkers in infants and children at different ages. The fact that resource
      rich postindustrial societies have a very low prevalence of iron-deficiency
      anemia offers hope that common types of anemia can be eliminated. In contrast,
      inborn forms of anemia, such as thalassemia, and anemias related to underlying
      diseases (e.g., bleeding tumors or peptic ulcers, gynecologic blood losses, or
      renal diseases) require an operational health system to be addressed
      appropriately.

PMID- 28507006
TI  - Perspective: Gluten-Free Products for Patients with Celiac Disease Should Not
      Contain Trace Levels.

PMID- 28507008
TI  - Flavones: Food Sources, Bioavailability, Metabolism, and Bioactivity.
AB  - Flavones are a class of flavonoids that are a subject of increasing interest
      because of their biological activities in vitro and in vivo. This article reviews
      the major sources of flavones and their concentrations in food and beverages,
      which vary widely between studies. It also covers the roles of flavones in
      plants, the influence of growing conditions on their concentrations, and their
      stability during food processing. The absorption and metabolism of flavones are
      also reviewed, in particular the intestinal absorption of both O- and C
      glycosides. Pharmacokinetic studies in both animals and humans are described,
      comparing differences between species and the effects of glycosylation on
      bioavailability. Biological activity in animal models and human dietary
      intervention studies is also reviewed. A better understanding of flavone sources
      and bioavailability is needed to understand mechanisms of action and nutritional
      intervention.

PMID- 28507007
TI  - Perspective: A Historical and Scientific Perspective of Sugar and Its Relation
      with Obesity and Diabetes.
AB  - Fructose-containing added sugars, such as sucrose and high-fructose corn syrup,
      have been experimentally, epidemiologically, and clinically shown to be involved
      in the current epidemics of obesity and diabetes. Here we track this history of
      intake of sugar as it relates to these epidemics. Key experimental studies that
      have identified mechanisms by which fructose causes obesity and diabetes are
      reviewed, as well as the evidence that the uricase mutation that occurred in the
      mid-Miocene in ancestral humans acted as a "thrifty gene" that increases our
      susceptibility for fructose-associated obesity today. We briefly review recent
      evidence that obesity can also be induced by nondietary sources of fructose, such
      as from the metabolism of glucose (from high-glycemic carbohydrates) through the
      polyol pathway. These studies suggest that fructose-induced obesity is driven by
      engagement of a "fat switch" and provide novel insights into new approaches for
      the prevention and treatment of these important diseases.

PMID- 28507009
TI  - A Systematic Examination of the Association between Parental and Child Obesity
      across Countries.
AB  - Childhood obesity has become a global epidemic. Parents can have an important
      influence on their children's health behaviors and weight status. Many studies
      have examined the association between parental and childhood weight status.
      However, much heterogeneity between studies exists, and the parent-child (P-C)
      association in obesity has varied. The purpose of this systematic examination and
      meta-analysis was to examine the strength and variation of the P-C association in
      obesity and to identify factors (e.g., demographic characteristics and country's
      economic level) that may influence this association. PubMed was searched for
      relevant studies published between January 2000 and July 2015. Thirty-two studies
      from 21 countries met inclusion criteria; 27 reported ORs for the P-C obesity
      association and were included in a meta-analysis. The meta-analysis showed a
      strong P-C obesity association (pooled OR: 2.22; 95% CI: 2.09, 2.36), which
      varied by type of P-C pair (i.e., parents-child, father-child, and mother-child),
      child age, parent and child weight status, and the country's economic level.
      Stronger associations were shown in older children than in younger children (beta
      +/- SE: 0.02 +/- 0.01), in both parents than in father only (beta +/- SE: 0.51 +/
      0.11) or mother only (beta +/- SE: 0.38 +/- 0.11), in parental obesity (beta +/-
      SE: 0.26 +/- 0.10) and child obesity (beta +/- SE: 0.28 +/- 0.12) than in
      parental and child overweight, and in high- than in middle-income countries (beta
      +/- SE: 0.23 +/- 0.08). Thus, research from multiple countries shows significant
      P-C associations in weight status, but this association varies by child age, type
      of P-C pair, weight status, and the country's economic level. Results suggest
      that families and parents should be a key target for obesity intervention
      efforts.

PMID- 28507010
TI  - A Systematic Review of Application and Effectiveness of mHealth Interventions for
      Obesity and Diabetes Treatment and Self-Management.
AB  - The use of mobile and wireless technologies and wearable devices for improving
      health care processes and outcomes (mHealth) is promising for health promotion
      among patients with chronic diseases such as obesity and diabetes. This study
      comprehensively examined published mHealth intervention studies for obesity and
      diabetes treatment and management to assess their effectiveness and provide
      recommendations for future research. We systematically searched PubMed for
      mHealth-related studies on diabetes and obesity treatment and management
      published during 2000-2016. Relevant information was extracted and analyzed.
      Twenty-four studies met inclusion criteria and varied in terms of sample size,
      ethnicity, gender, and age of the participating patients and length of follow-up.
      The mHealth interventions were categorized into 3 types: mobile phone text
      messaging, wearable or portable monitoring devices, and applications running on
      smartphones. Primary outcomes included weight loss (an average loss ranging from 
      1.97 kg in 16 wk to -7.1 kg in 5 wk) or maintenance and blood glucose reduction
      (an average decrease of glycated hemoglobin ranging from -0.4% in 10 mo to -1.9%
      in 12 mo); main secondary outcomes included behavior changes and patient
      perceptions such as self-efficacy and acceptability of the intervention programs.
      More than 50% of studies reported positive effects of interventions based on
      primary outcomes. The duration or length of intervention ranged from 1 wk to 24
      mo. However, most studies included small samples and short intervention periods
      and did not use rigorous data collection or analytic approaches. Although some
      studies suggest that mHealth interventions are effective and promising, most are
      pilot studies or have limitations in their study designs. There is an essential
      need for future studies that use larger study samples, longer intervention (>= 6
      mo) and follow-up periods (>= 6 mo), and integrative and personalized innovative
      mobile technologies to provide comprehensive and sustainable support for patients
      and health service providers.

PMID- 28507011
TI  - Influence of Diet in Multiple Sclerosis: A Systematic Review.
AB  - Nutrition is considered to be a possible factor in the pathogenesis of the
      neurological disease multiple sclerosis (MS). Nutrition intervention studies
      suggest that diet may be considered as a complementary treatment to control the
      progression of the disease; a systematic review of the literature on the
      influence of diet on MS was therefore conducted. The literature search was
      conducted by using Medlars Online International Literature (MEDLINE) via PubMed
      and Scopus. Forty-seven articles met the inclusion criteria. The reviewed
      articles assessed the relations between macro- and micronutrient intakes and MS
      incidence. The patients involved used alternative therapies (homeopathy),
      protocolized diets that included particular foods (herbal products such as grape
      seed extract, ginseng, blueberries, green tea, etc.), or dietary supplements such
      as vitamin D, carnitine, melatonin, or coenzyme Q10. Current studies suggest that
      high serum concentrations of vitamin D, a potent immunomodulator, may decrease
      the risk of MS and the risk of relapse and new lesions, while improving brain
      lesions and timed tandem walking. Experimental evidence suggests that serum
      vitamin D concentration is lower during MS relapses than in remission and is
      associated with a greater degree of disability [Expanded Disability Status Scale
      (EDSS) score >3]. The findings suggest that circulating vitamin D concentrations
      can be considered a biomarker of MS and supplemental vitamin D can be used
      therapeutically. Other studies point to a negative correlation between serum
      vitamin B-12 concentrations and EDSS score. Vitamin B-12 has fundamental roles in
      central nervous system function, especially in the methionine synthase-mediated
      conversion of homocysteine to methionine, which is essential for DNA and RNA
      synthesis. Therefore, vitamin B-12 deficiency may lead to an increase in the
      concentration of homocysteine. Further research is clearly necessary to determine
      whether treatment with vitamin B-12 supplements delays MS progression.

PMID- 28507012
TI  - Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis.
AB  - Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity
      to dissociate cellular respiration from ATP utilization, resulting in the release
      of stored energy as heat. Adult humans possess a substantial amount of BAT in the
      form of constitutively active brown fat or inducible beige fat. BAT activity in
      humans is inversely correlated with adiposity, blood glucose concentrations, and
      insulin sensitivity; this suggests that strategies aimed at BAT-mediated
      bioenergetics are an attractive therapeutic target in combating the continuing
      epidemic of obesity and diabetes. Despite advances in knowledge regarding the
      developmental lineage and transcriptional regulators of brown and beige
      adipocytes, our current understanding of environmental modifiers of BAT
      thermogenesis, such as diet, is limited. In this review, we consolidated the
      latest research on dietary molecules that may serve to promote BAT thermogenesis.
      Here, we summarized the thermogenic function of selected phytochemicals (e.g.,
      capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids
      (e.g., fish oil and conjugated linoleic acids), and all-trans retinoic acid, a
      vitamin A metabolite. We also delineated the proposed mechanisms whereby these
      dietary molecules promote BAT activity and/or browning of white adipose tissue.
      Characterizing thermogenic dietary factors may offer novel insight into revising
      nutritional intervention strategies aimed at obesity and diabetes prevention and
      management.

PMID- 28507017
TI  - Erratum for Rippe. The metabolic and endocrine response and health implications
      of consuming sugar-sweetened beverages: findings from recent randomized
      controlled trials. Adv Nutr 2013;4:677-86.

PMID- 28507018
TI  - Erratum for Rippe and Angelopoulos. Fructose-containing sugars and cardiovascular
      disease. Adv Nutr 2015;6:430-9.

PMID- 28507016
TI  - Manganese.

PMID- 28507013
TI  - Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut
      Motility and Constipation.
AB  - Constipation is a common and burdensome gastrointestinal disorder that may result
      from altered gastrointestinal motility. The effect of probiotics on constipation
      has been increasingly investigated in both animal and human studies, showing
      promising results. However, there is still uncertainty regarding the mechanisms
      of action of probiotics on gut motility and constipation. Several factors are
      vital to normal gut motility, including immune and nervous system function, bile
      acid metabolism and mucus secretion, and the gastrointestinal microbiota and
      fermentation; an imbalance or dysfunction in any of these components may
      contribute to aberrant gut motility and, consequently, symptoms of constipation.
      For example, adults with functional constipation have significantly decreased
      numbers of bifidobacteria (with one study showing a mean difference of 1 log10/g)
      and lactobacilli (mean difference, 1.4 log10/g) in stool samples, as well as
      higher breath methane, compared with control subjects. Modifying the gut luminal
      environment with certain probiotic strains may affect motility and secretion in
      the gut and, hence, provide a benefit for patients with constipation. Therefore,
      this review explores the mechanisms through which probiotics may exert an effect
      on gut motility and constipation. Nevertheless, the majority of current evidence
      is derived from animal studies, and therefore, further human studies are needed
      to determine the mechanisms through specific probiotic strains that might be
      effective in constipation.

PMID- 28507014
TI  - Associations between Breastfeeding and Maternal Responsiveness: A Systematic
      Review of the Literature.
AB  - Recent recommendations and prevention programs have focused on the promotion of
      responsive feeding during infancy, but more research is needed to understand best
      practices for fostering responsive feeding during early life. The objective of
      this systematic review was to synthesize the accumulating bodies of evidence
      aimed at understanding associations between mothers' feeding experiences and
      responsive feeding in an attempt to clarify the nature of associations between
      feeding mode and responsive feeding. A literature search was conducted between
      January and October 2016; articles were collected from PsychINFO, Medline, and
      CINAHL, as well as from references in published research and reviews. Article
      inclusion criteria were as follows: 1) empirical research, 2) included a measure
      of infant feeding, 3) included a measure of maternal responsiveness, 4) study
      conducted in human participants, 5) available in English, and 6) study conducted
      in a developed and/or high-income country. Forty-three studies were identified.
      Cross-sectional observational studies consistently reported greater
      responsiveness among breastfeeding mothers than among formula-/bottle-feeding
      mothers. In addition, longitudinal studies showed that longer breastfeeding
      durations predicted lower use of nonresponsive feeding practices during later
      childhood, and some, but not all, found that breastfeeding mothers showed greater
      increases in responsiveness across infancy than did formula-/bottle-feeding
      mothers. However, a limited number of longitudinal studies also reported that
      greater responsiveness during early infancy predicted longer breastfeeding
      durations. A common limitation among these studies is the correlational nature of
      their designs and lack of prenatal measures of maternal responsiveness, which
      hinders our understanding of causal mechanisms. Although 2 randomized clinical
      trials aimed at promoting maternal responsiveness did not find effects of the
      intervention on breastfeeding outcomes, these findings were limited by the way in
      which breastfeeding outcomes were assessed. In sum, although there is consistent
      evidence for an association between breastfeeding and responsive feeding, more
      research is needed to better understand the mechanisms underlying this
      association.

PMID- 28507019
TI  - Major global cyber-attack hits NHS and delays treatment.

PMID- 28507015
TI  - Preserving Healthy Muscle during Weight Loss.
AB  - Weight loss is the cornerstone of therapy for people with obesity because it can
      ameliorate or completely resolve the metabolic risk factors for diabetes,
      coronary artery disease, and obesity-associated cancers. The potential health
      benefits of diet-induced weight loss are thought to be compromised by the weight
      loss-associated loss of lean body mass, which could increase the risk of
      sarcopenia (low muscle mass and impaired muscle function). The objective of this
      review is to provide an overview of what is known about weight-loss-induced
      muscle loss and its implications for overall physical function (e.g., ability to
      lift items, walk, and climb stairs). The currently available data in the
      literature show the following: 1) compared with persons with normal weight, those
      with obesity have more muscle mass but poor muscle quality; 2) diet-induced
      weight loss reduces muscle mass without adversely affecting muscle strength; 3)
      weight loss improves global physical function, most likely because of reduced fat
      mass; 4) high protein intake helps preserve lean body and muscle mass during
      weight loss but does not improve muscle strength and could have adverse effects
      on metabolic function; 5) both endurance- and resistance-type exercise help
      preserve muscle mass during weight loss, and resistance-type exercise also
      improves muscle strength. We therefore conclude that weight-loss therapy,
      including a hypocaloric diet with adequate (but not excessive) protein intake and
      increased physical activity (particularly resistance-type exercise), should be
      promoted to maintain muscle mass and improve muscle strength and physical
      function in persons with obesity.

PMID- 28507020
TI  - TGF-beta Family Signaling in Mesenchymal Differentiation.
AB  - Mesenchymal stem cells (MSCs) can differentiate into several lineages during
      development and also contribute to tissue homeostasis and regeneration, although
      the requirements for both may be distinct. MSC lineage commitment and progression
      in differentiation are regulated by members of the transforming growth factor
      beta (TGF-beta) family. This review focuses on the roles of TGF-beta family
      signaling in mesenchymal lineage commitment and differentiation into osteoblasts,
      chondrocytes, myoblasts, adipocytes, and tenocytes. We summarize the reported
      findings of cell culture studies, animal models, and interactions with other
      signaling pathways and highlight how aberrations in TGF-beta family signaling can
      drive human disease by affecting mesenchymal differentiation.

PMID- 28507022
TI  - Loss of E-Cadherin-Dependent Cell-Cell Adhesion and the Development and
      Progression of Cancer.
AB  - Classical cadherins are the key molecules that control cell-cell adhesion.
      Notwithstanding this function, it is also clear that classical cadherins are more
      than just the "glue" that keeps the cells together. Cadherins are essential
      regulators of tissue homeostasis that govern multiple facets of cellular function
      and development, by transducing adhesive signals to a complex network of
      signaling effectors and transcriptional programs. In cancer, cadherins are often
      inactivated or functionally inhibited, resulting in disease development and/or
      progression. This review focuses on E-cadherin and its causal role in the
      development and progression of breast and gastric cancer. We provide a summary of
      the biochemical consequences and consider the conceptual impact of early
      (mutational) E-cadherin loss in cancer. We advocate that carcinomas driven by E
      cadherin loss should be considered "actin-diseases," caused by the specific
      disruption of the E-cadherin-actin connection and a subsequent dependence on
      sustained actomyosin contraction for tumor progression. Based on the available
      data from mouse and human studies we discuss opportunities for targeted clinical
      intervention.

PMID- 28507021
TI  - Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease.
AB  - Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium
      establishes a selectively permeable barrier that supports nutrient absorption and
      waste secretion while preventing intrusion by luminal materials. Intestinal
      epithelia therefore play a central role in regulating interactions between the
      mucosal immune system and luminal contents, which include dietary antigens, a
      diverse intestinal microbiome, and pathogens. The paracellular space is sealed by
      the tight junction, which is maintained by a complex network of protein
      interactions. Tight junction dysfunction has been linked to a variety of local
      and systemic diseases. Two molecularly and biophysically distinct pathways across
      the intestinal tight junction are selectively and differentially regulated by
      inflammatory stimuli. This review discusses the mechanisms underlying these
      events, their impact on disease, and the potential of using these as paradigms
      for development of tight junction-targeted therapeutic interventions.

PMID- 28507023
TI  - Increases in Biomarkers of Hyperglycemia With Age in the Atherosclerosis Risk in
      Communities (ARIC) Study.

PMID- 28507024
TI  - Cutting Edge: Differential Fine-Tuning of IL-2- and IL-15-Dependent Functions by
      Targeting Their Common IL-2/15Rbeta/gammac Receptor.
AB  - Interleukin 2 and IL-15 are two closely related cytokines, displaying important
      functions in the immune system. They share the heterodimeric CD122/CD132 receptor
      to deliver their signals within target cells. Their specificity of action is
      conferred by their alpha receptor chains, IL-2Ralpha and IL-15Ralpha. By
      combining an increased affinity for CD122 and an impaired recruitment of CD132,
      we have generated an original molecule named IL-2Rbeta/gamma (CD122/CD132)
      inhibitor (BiG), targeting the CD122/CD132 receptor. BiG efficiently inhibited IL
      15- and IL-2-dependent functions of primary cells, including CD8 T and NK cells,
      in vitro and in vivo. We also report a differential dynamic of action of these
      cytokines by highlighting a major role played by the IL-2Ralpha receptor.
      Interestingly, due to the presence of IL-2Ralpha, BiG had no impact on IL-2
      dependent regulatory T cell proliferation. Thus, by acting as a fine switch in
      the immune system, BiG emphasizes the differential roles of these two cytokines.

PMID- 28507025
TI  - Cutting Edge: Defective Aerobic Glycolysis Defines the Distinct Effector Function
      in Antigen-Activated CD8+ Recent Thymic Emigrants.
AB  - Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have
      completed thymic selection and egress to the lymphoid periphery. RTEs are
      functionally distinct from their more mature but still naive T cell counterparts,
      because they exhibit dampened proliferation and reduced cytokine production upon
      activation. In this article, we show that, compared with more mature but still
      naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis
      following activation. Impaired metabolism underlies the reduced IFN-gamma
      production observed in activated RTEs. This failure to undergo Ag-induced aerobic
      glycolysis is caused by reduced mTORC1 activity and diminished Myc induction in
      RTEs. Critically, exogenous IL-2 restores Myc expression in RTEs, driving aerobic
      glycolysis and IFN-gamma production to the level of mature T cells. These results
      reveal a previously unknown metabolic component to postthymic T cell maturation.

PMID- 28507027
TI  - Mycobacterium tuberculosis Lipoprotein MPT83 Induces Apoptosis of Infected
      Macrophages by Activating the TLR2/p38/COX-2 Signaling Pathway.
AB  - Tuberculosis caused by Mycobacterium tuberculosis continues to pose a serious
      global health threat. The attenuated Mycobacterium bovis bacillus Calmette
      Guerin, as the only licensed vaccine, has limited protective efficacy against TB.
      The development of more effective antituberculosis vaccines is urgent and demands
      for further identification and understanding of M. tuberculosis Ags. MPT83
      (Rv2873), a secreted mycobacterial lipoprotein, has been applied into subunit
      vaccine development and shown protective effects against M. tuberculosis
      infection in animals; however, the understanding of the underlying mechanism is
      limited. In present study, we systematically studied the effect of MPT83 on
      macrophage apoptosis by constructing Mycobacterium smegmatis strain
      overexpressing MPT83 (MS_MPT83) and purifying rMPT83 protein. We found that MPT83
      induced apoptosis in both human and mouse macrophages. MPT83 induced
      cyclooxygenase-2 (COX-2) expression at both the transcriptional and protein
      levels in macrophages, whereas silencing or inhibiting COX-2 blocked rMPT83
      induced apoptosis or the enhanced apoptotic response to MS_MPT83 in comparison
      with M. smegmatis transfected with pMV261 vector (MS_Vec), indicating that COX-2
      is required for MPT83-induced apoptosis. Additionally, tlr2 deficiency led to
      significant reduction of COX-2 expression, accompanied by less apoptosis in
      macrophages stimulated with rMPT83 or infected with MS_MPT83. Moreover, the
      activation of p38 accounted for MPT83-induced COX-2 expression. Finally, lower
      bacteria burdens in the lungs and spleens and enhanced survival were observed in
      mice i.v. infected with MS_MPT83 compared with MS_Vec. Taken together, our
      results established a proapoptotic effect of MPT83 and identified the
      TLR2/p38/COX-2 axis in MPT83-induced macrophage apoptosis.

PMID- 28507028
TI  - RIG-I-like Receptor Triggering by Dengue Virus Drives Dendritic Cell Immune
      Activation and TH1 Differentiation.
AB  - Dengue virus (DENV) causes 400 million infections annually and is one of several
      viruses that can cause viral hemorrhagic fever, which is characterized by
      uncontrolled immune activation resulting in high fever and internal bleeding.
      Although the underlying mechanisms are unknown, massive cytokine secretion is
      thought to be involved. Dendritic cells (DCs) are the main target cells of DENV,
      and we investigated their role in DENV-induced cytokine production and adaptive
      immune responses. DENV infection induced DC maturation and secretion of IL-1beta,
      IL-6, and TNF. Inhibition of DENV RNA replication abrogated these responses.
      Notably, silencing of RNA sensors RIG-I or MDA5 abrogated DC maturation, as well
      as cytokine responses by DENV-infected DCs. DC maturation was induced by type I
      IFN responses because inhibition of IFN-alpha/beta receptor signaling abrogated
      DENV-induced DC maturation. Moreover, DENV infection of DCs resulted in CCL2,
      CCL3, and CCL4 expression, which was abrogated after RIG-I and MDA5 silencing.
      DCs play an essential role in TH cell differentiation, and we show that RIG-I and
      MDA5 triggering by DENV leads to TH1 polarization, which is characterized by high
      levels of IFN-gamma. Notably, cytokines IL-6, TNF, and IFN-gamma and chemokines
      CCL2, CCL3, and CCL4 have been associated with disease severity, endothelial
      dysfunction, and vasodilation. Therefore, we identified RIG-I and MDA5 as
      critical players in innate and adaptive immune responses against DENV, and
      targeting these receptors has the potential to decrease hemorrhagic fever in
      patients.

PMID- 28507026
TI  - Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the
      Demyelinating Central Nervous System.
AB  - Multiple sclerosis (MS) is a disease that is characterized by immune-mediated
      destruction of CNS myelin. Current MS therapies aim to block peripheral immune
      cells from entering the CNS. Although these treatments limit new inflammatory
      activity in the CNS, no treatment effectively prevents long-term disease
      progression and disability accumulation in MS patients. One explanation for this
      paradox is that current therapies are ineffective at targeting immune responses
      already present in the CNS. To this end, we sought to understand the metabolic
      properties of T cells that mediate ongoing inflammation in the demyelinating CNS.
      Using experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a well
      studied model of MS, we showed that the CD4+ and CD8+ T cells that invade the EAE
      CNS are highly glycolytic. Elevated glycolytic rates in T cells isolated from the
      EAE CNS correlate with upregulated expression of glycolytic machinery and is
      essential for inflammatory responses to myelin. Surprisingly, we found that an
      inhibitor of GAPDH, 3-bromopyruvic acid (3-BrPa), blocks IFN-gamma, but not IL
      17A, production in immune cells isolated from the EAE CNS. Indeed, in vitro
      studies confirmed that the production of IFN-gamma by differentiated Th1 cells is
      more sensitive to 3-BrPa than is the production of IL-17A by Th17 cells. Finally,
      in transfer models of EAE, 3-BrPa robustly attenuates the encephalitogenic
      potential of EAE-driving immune cells. To our knowledge, these data are among the
      first to demonstrate the metabolic properties of T cells in the demyelinating CNS
      in vivo.

PMID- 28507029
TI  - CD63-Mediated Antigen Delivery into Extracellular Vesicles via DNA Vaccination
      Results in Robust CD8+ T Cell Responses.
AB  - DNA vaccines are attractive immunogens for priming humoral and cellular immune
      responses to the encoded Ag. However, their ability to induce Ag-specific CD8+ T
      cell responses requires improvement. Among the strategies for improving DNA
      vaccine immunogenicity are booster vaccinations, alternate vaccine formulations,
      electroporation, and genetic adjuvants, but few, such as extracellular vesicles
      (EVs), target natural Ag delivery systems. By focusing on CD63, a tetraspanin
      protein expressed on various cellular membranes, including EVs, we examined
      whether a DNA vaccine encoding an Ag fused to CD63 delivered into EVs would
      improve vaccine immunogenicity. In vitro transfection with plasmid DNA encoding
      an OVA Ag fused to CD63 (pCD63-OVA) produced OVA-carrying EVs. Immunizations with
      the purified OVA-carrying EVs primed naive mice to induce OVA-specific CD4+ and
      CD8+ T cells, whereas immunization with EVs purified from cells transfected with
      control plasmids encoding OVA protein alone or a calnexin-OVA fusion protein
      delivered into the endoplasmic reticulum failed to do so. Vaccinating mice with
      pCD63-OVA induced potent Ag-specific T cell responses, particularly those from
      CD8+ T cells. CD63 delivery into EVs led to better CD8+ T cell responses than
      calnexin delivery into the endoplasmic reticulum. When we used a mouse tumor
      implantation model to evaluate pCD63-OVA as a therapeutic vaccine, the EV
      delivered DNA vaccination significantly inhibited tumor growth compared with the
      control DNA vaccinations. These results indicate that EV Ag delivery via DNA
      vaccination offers a new strategy for eliciting strong CD8+ T cell responses to
      the encoded Ag, making it a potentially useful cancer vaccine.

PMID- 28507030
TI  - CCR2 Regulates the Immune Response by Modulating the Interconversion and Function
      of Effector and Regulatory T Cells.
AB  - Chemokines and chemokine receptors establish a complex network modulating immune
      cell migration and localization. These molecules were also suggested to mediate
      the differentiation of leukocytes; however, their intrinsic, direct regulation of
      lymphocyte fate remained unclear. CCR2 is the main chemokine receptor inducing
      macrophage and monocyte recruitment to sites of inflammation, and it is also
      expressed on T cells. To assess whether CCR2 directly regulates T cell responses,
      we followed the fates of CCR2-/- T cells in T cell-specific inflammatory models.
      Our in vitro and in vivo results show that CCR2 intrinsically mediates the
      expression of inflammatory T cell cytokines, and its absence on T cells results
      in attenuated colitis progression. Moreover, CCR2 deficiency in T cells promoted
      a program inducing the accumulation of Foxp3+ regulatory T cells, while
      decreasing the levels of Th17 cells in vivo, indicating that CCR2 regulates the
      immune response by modulating the effector/regulatory T ratio.

PMID- 28507031
TI  - Memory consolidation within the central amygdala is not necessary for modulation
      of cerebellar learning.
AB  - Amygdala lesions impair, but do not prevent, acquisition of cerebellum-dependent
      eyeblink conditioning suggesting that the amygdala modulates cerebellar learning.
      Two-factor theories of eyeblink conditioning posit that a fast-developing memory
      within the amygdala facilitates slower-developing memory within the cerebellum.
      The current study tested this hypothesis by impairing memory consolidation within
      the amygdala with inhibition of protein synthesis, transcription, and NMDA
      receptors in rats. Rats given infusions of anisomycin or DRB into the central
      amygdala (CeA) immediately after each eyeblink conditioning session were severely
      impaired in contextual and cued fear conditioning, but were completely unimpaired
      in eyeblink conditioning. Rats given the NMDA antagonist ifenprodil into the CeA
      before each eyeblink conditioning session also showed impaired fear conditioning,
      but no deficit in eyeblink conditioning. The results indicate that memory
      formation within the CeA is not necessary for its modulation of cerebellar
      learning mechanisms. The CeA may modulate cerebellar learning and retention
      through an attentional mechanism that develops within the training sessions.

PMID- 28507033
TI  - Response-specific sex difference in the retention of fear extinction.
AB  - Fear conditioning studies in rodents allow us to assess vulnerability factors
      which might underlie fear-based psychopathology such as post-traumatic stress
      disorder (PTSD). Despite PTSD being more prevalent in females than males, very
      few fear conditioning studies in rodents have tested females. Our study assessed
      fear conditioning and extinction in male and female rats using both fear
      potentiated startle and freezing behavior as measures. Rats were trained to fear
      cues that predicted the occurrence of shock and then subsequently exposed to an
      extinction training procedure where the cue was presented repeatedly in the
      absence of shock. Retention of the extinction memory was assessed the next day.
      Our results showed that females exhibited less retention of fear extinction, but
      only when measured by fear-potentiated startle. Our results highlight the
      importance of using multiple indices of fear behavior, particularly when
      comparing sexes on measures of extinction learning.

PMID- 28507034
TI  - Sleep supports inhibitory operant conditioning memory in Aplysia.
AB  - Sleep supports memory consolidation as shown in mammals and invertebrates such as
      bees and Drosophila. Here, we show that sleep's memory function is preserved in
      Aplysia californica with an even simpler nervous system. Animals performed on an
      inhibitory conditioning task ("learning that a food is inedible") three times, at
      Training, Retrieval 1, and Retrieval 2, with 17-h intervals between tests.
      Compared with Wake animals, remaining awake between Training and Retrieval 1,
      Sleep animals with undisturbed post-training sleep, performed significantly
      better at Retrieval 1 and 2. Control experiments testing retrieval only after ~34
      h, confirmed the consolidating effect of sleep occurring within 17 h after
      training.

PMID- 28507032
TI  - alpha2* Nicotinic acetylcholine receptors influence hippocampus-dependent
      learning and memory in adolescent mice.
AB  - The absence of alpha2* nicotinic acetylcholine receptors (nAChRs) in oriens
      lacunosum moleculare (OLM) GABAergic interneurons ablate the facilitation of
      nicotine-induced hippocampal CA1 long-term potentiation and impair memory. The
      current study delineated whether genetic mutations of alpha2* nAChRs
      (Chrna2L9'S/L9'S and Chrna2KO) influence hippocampus-dependent learning and
      memory and CA1 synaptic plasticity. We substituted a serine for a leucine (L9'S)
      in the alpha2 subunit (encoded by the Chrna2 gene) to make a hypersensitive
      nAChR. Using a dorsal hippocampus-dependent task of preexposure-dependent
      contextual fear conditioning, adolescent hypersensitive Chrna2L9'S/L9'S male mice
      exhibited impaired learning and memory. The deficit was rescued by low-dose
      nicotine exposure. Electrophysiological studies demonstrated that hypersensitive
      alpha2 nAChRs potentiate acetylcholine-induced ion channel flux in oocytes and
      acute nicotine-induced facilitation of dorsal/intermediate CA1 hippocampal long
      term potentiation in Chrna2L9'S/L9'S mice. Adolescent male mice null for the
      alpha2 nAChR subunit exhibited a baseline deficit in learning that was not
      reversed by an acute dose of nicotine. These effects were not influenced by
      locomotor, sensory or anxiety-related measures. Our results demonstrated that
      alpha2* nAChRs influenced hippocampus-dependent learning and memory, as well as
      nicotine-facilitated CA1 hippocampal synaptic plasticity.

PMID- 28507035
TI  - Long-term sensitization training in Aplysia decreases the excitability of a
      decision-making neuron through a sodium-dependent mechanism.
AB  - In Aplysia, long-term sensitization (LTS) occurs concurrently with a suppression
      of feeding. At the cellular level, the suppression of feeding is accompanied by
      decreased excitability of decision-making neuron B51. We examined the
      contribution of voltage-gated Na+ and K+ channels to B51 decreased excitability.
      In a pharmacologically isolated Na+ channels environment, LTS training
      significantly increased B51 firing threshold, compared with untrained controls.
      Conversely, in a pharmacologically isolated K+ channels environment, no
      differences were observed between trained and untrained animals in either
      amplitude or area of B51 K+-dependent depolarizations. These findings suggest
      that Na+ channels contribute to the decrease in B51 excitability induced by LTS
      training.

PMID- 28507036
TI  - Medial prefrontal cortex and dorsomedial striatum are necessary for the trial
      unique, delayed nonmatching-to-location (TUNL) task in rats: role of NMDA
      receptors.
AB  - The trial-unique, delayed nonmatching-to-location (TUNL) task is a recently
      developed behavioral task that measures spatial working memory and a form of
      pattern separation in touchscreen-equipped operant conditioning chambers. Limited
      information exists regarding the neurotransmitters and neural substrates involved
      in the task. The present experiments tested the effects of systemic and
      intracranial injections of NMDA receptor antagonists on the TUNL task. After
      training, male Long Evans rats systemically injected with the competitive NMDA
      receptor antagonist CPP (10 mg/kg) had impaired accuracy regardless of the degree
      of stimuli separation or length of delay between the sample and test phases.
      Injections of Ro 25-6981 (6 or 10 mg/kg), an antagonist selective for GluN2B
      subunit-containing NMDA receptors, did not affect accuracy on the task. Direct
      infusion of the competitive NMDA receptor antagonist AP5 into mPFC or dmSTR
      reduced overall accuracy on the TUNL task. These results demonstrate that TUNL
      task performance depends on NMDA receptors within the mPFC and dmSTR.

PMID- 28507037
TI  - Systemic Activation of NRF2 Alleviates Lethal Autoimmune Inflammation in Scurfy
      Mice.
AB  - The transcription factor NRF2 (nuclear factor [erythroid-derived 2]-like 2) plays
      crucial roles in the defense mechanisms against oxidative stress and mediates
      anti-inflammatory actions under various pathological conditions. Recent studies
      showed that the dysfunction of regulatory T cells (Tregs) is directly linked to
      the initiation and progression of various autoimmune diseases. To determine the
      Treg-independent impact of NRF2 activation on autoimmune inflammation, we
      examined scurfy (Sf) mice, which are deficient in Tregs and succumb to severe
      multiorgan inflammation by 4 weeks of age. We found that systemic activation of
      NRF2 by Keap1 (Kelch-like ECH-associated protein 1) knockdown ameliorated tissue
      inflammation and lethality in Sf mice. Activated T cells and their cytokine
      production were accordingly decreased by Keap1 knockdown. In contrast, NRF2
      activation through cell lineage-specific Keap1 disruption (i.e., in T cells,
      myeloid cells, and dendritic cells) achieved only partial or no improvement in
      the inflammatory status of Sf mice. Our results indicate that systemic activation
      of NRF2 suppresses effector T cell activities independently of Tregs and that
      NRF2 activation in multiple cell lineages appears to be required for sufficient
      anti-inflammatory effects. This study emphasizes the possible therapeutic
      application of NRF2 inducers in autoimmune diseases that are accompanied by Treg
      dysfunction.

PMID- 28507038
TI  - High-affinity pan-specific monoclonal antibodies that target cysteinyl
      leukotrienes and show efficacy in an acute model of colitis.
AB  - Cysteinyl leukotrienes (CysLTs) are a small family of biological signaling lipids
      produced by active leukocytes that contribute to diverse inflammatory disease
      states as a consequence of their engagement with dedicated G protein-coupled
      receptors. Immunization of mice with a CysLT-modified hapten carrier protein
      yielded novel monoclonal antibodies that display variable binding affinity to
      CysLTs. Solution binding assays indicated differing specificities among the
      antibodies tested, with antibody 10G4 displaying a preference for leukotriene C4
      (LTC4). X-ray crystallography of a humanized 10G4 Fab fragment in complex with
      LTC4 revealed that binding induces a hook-like conformation within the
      hydrocarbon tail of the lipid arachidonic acid moiety. Specific hydrogen bonding
      to the LTC4 carboxylate groups further stabilized the complex, while a water
      molecule mediated a hydrogen bond network that connected the N-terminal arm of l
      glutathione to both the arachidonyl carboxylate of LTC4 and the antibody heavy
      chain. Prophylactic administration of two anti-CysLT antibodies in mice followed
      by challenge with LTC4 demonstrated their in vivo efficacy against acute
      inflammation in a vascular permeability model. 10G4 ameliorated the effects of
      acute dextran sulfate sodium-induced colitis, suggesting that anti-CysLT
      antibodies could provide a therapeutic benefit in the treatment of inflammatory
      diseases.

PMID- 28507041
TI  - Publisher's Note - Relating to the retraction of: Oxidative stress inactivates
      VEGF survival signaling in retinal endothelial cells via PI 3-kinase tyrosine
      nitration. Azza B. El-Remessy, Manuela Bartoli, Danial H. Platt, David Fulton,
      Ruth B. Caldwell. J. Cell Sci. doi:10.1242/jcs.195966.

PMID- 28507039
TI  - Do Aspirin and Other NSAIDs Confer a Survival Benefit in Men Diagnosed with
      Prostate Cancer? A Pooled Analysis of NIH-AARP and PLCO Cohorts.
AB  - Prostate cancer is one of the leading causes of cancer-related death in U.S. men.
      There is an unmet need to identify modifiable risk factors for prostate cancer
      survival. Experimental studies have suggested that nonsteroidal anti-inflammatory
      drugs (NSAIDs) may improve prostate cancer survival through antithrombotic and
      anti-inflammation mechanisms. Results from previous observational studies have
      been equivocal, and few have assessed whether an etiologically relevant time
      window of exposure exists. We sampled incident prostate cancer cases from two
      large U.S. prospective cohorts, NIH-AARP Diet and Health Study and PLCO Cancer
      Screening Trial, to investigate whether pre- and postdiagnostic aspirin and non
      aspirin NSAID use were associated with prostate cancer-specific and all-cause
      mortality. Cox proportional hazards regression models estimated hazard ratios
      (HRs) and 95% confidence intervals (CIs). Study-specific results were meta
      analyzed using fixed-effects models. Pre- and postdiagnostic aspirin or non
      aspirin NSAID use were not statistically significantly associated with prostate
      cancer-specific mortality. However, occasional (less than daily) and daily
      aspirin users five years or more before prostate cancer diagnosis had 18% (HR =
      0.82; 95% CI = 0.75-0.90) and 15% (HR = 0.85; 95% CI = 0.77-0.94) reduced all
      cause mortality versus nonusers. Similarly, postdiagnostic occasional and daily
      aspirin use were associated with 17% (HR = 0.83; 95% CI=0.72-0.95) and 25% (HR =
      0.75; 95% CI = 0.66-0.86) reduced all-cause mortality, independent of
      prediagnostic aspirin use. This study suggests that aspirin or non-aspirin NSAIDs
      are not associated with prostate cancer survival. However, aspirin use both
      before and after prostate cancer diagnosis was associated with longer overall
      survival, highlighting the importance of comorbidity prevention among prostate
      cancer survivors. Cancer Prev Res; 10(7); 410-20. (c)2017 AACR.

PMID- 28507049
TI  - Models in Translational Oncology: A Public Resource Database for Preclinical
      Cancer Research.
AB  - The devastating diseases of human cancer are mimicked in basic and translational
      cancer research by a steadily increasing number of tumor models, a situation
      requiring a platform with standardized reports to share model data. Models in
      Translational Oncology (MiTO) database was developed as a unique Web platform
      aiming for a comprehensive overview of preclinical models covering genetically
      engineered organisms, models of transplantation, chemical/physical induction, or
      spontaneous development, reviewed here. MiTO serves data entry for metastasis
      profiles and interventions. Moreover, cell lines and animal lines including tool
      strains can be recorded. Hyperlinks for connection with other databases and file
      uploads as supplementary information are supported. Several communication tools
      are offered to facilitate exchange of information. Notably, intellectual property
      can be protected prior to publication by inventor-defined accessibility of any
      given model. Data recall is via a highly configurable keyword search. Genome
      editing is expected to result in changes of the spectrum of model organisms, a
      reason to open MiTO for species-independent data. Registered users may deposit
      own model fact sheets (FS). MiTO experts check them for plausibility.
      Independently, manually curated FS are provided to principle investigators for
      revision and publication. Importantly, noneditable versions of reviewed FS can be
      cited in peer-reviewed journals. Cancer Res; 77(10); 2557-63. (c)2017 AACR.

PMID- 28507051
TI  - Correction: Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and
      Autophagy in Ovarian Cancer and Melanoma.

PMID- 28507052
TI  - Correction: Pulsed High-Intensity Focused Ultrasound Enhances Delivery of
      Doxorubicin in a Preclinical Model of Pancreatic Cancer.

PMID- 28507053
TI  - Correction: Metastatic Progression of Prostate Cancer Is Mediated by Autonomous
      Binding of Galectin-4-O-Glycan to Cancer Cells.

PMID- 28507050
TI  - Tumor Dormancy and Relapse: From a Natural Byproduct of Evolution to a Disease
      State.
AB  - Species evolve by mutations and epigenetic changes acting on individuals in a
      population; tumors evolve by similar mechanisms at a cellular level in a tissue.
      This article reviews growing evidence about tumor dormancy and suggests that (i)
      cellular malignancy is a natural byproduct of evolutionary mechanisms, such as
      gene mutations and epigenetic modifications, which is manifested in the form of
      tumor dormancy in healthy individuals as well as in cancer survivors; (ii) cancer
      metastasis could be an early dissemination event that could occur during
      malignant dormancy even before primary cancer is clinically detectable; and (iii)
      chronic inflammation is a key factor in awakening dormant malignant cells at the
      primary site, leading to primary cancer development, and at distant sites,
      leading to advanced stage diseases. On the basis of this evidence, it is
      reasonable to propose that we are all cancer survivors rather than cancer-free
      individuals because of harboring dormant malignant cells in our organs. A better
      understanding of local and metastatic tumor dormancy could lead to novel cancer
      therapeutics for the prevention of cancer. Cancer Res; 77(10); 2564-9. (c)2017
      AACR.

PMID- 28507055
TI  - Adhesion and friction of the smooth attachment system of the cockroach
      Gromphadorhina portentosa and the influence of the application of fluid
      adhesives.
AB  - Two different measurement techniques were applied to study the attachment of the
      smooth foot pads of the Madagascar hissing cockroach Gromphadorhina portentosa
      The attachment of the non-manipulated adhesive organs was compared with that of
      manipulated ones (depletion or substitution by artificial secretions). From
      measurements of the friction on a centrifuge, it can be concluded that on
      nanorough surfaces, the insect appears to benefit from employing emulsions
      instead of pure oils to avoid excessive friction. Measurements performed with a
      nanotribometer on single attachment organs showed that, in the non-manipulated
      euplantulae, friction was clearly increased in the push direction, whereas the
      arolium of the fore tarsus showed higher friction in the pull direction. The
      surface of the euplantulae shows an imbricate appearance, whereupon the ledges
      face distally, which might contribute to the observed frictional anisotropy in
      the push direction. Upon depletion of the tarsal adhesion-mediating secretion or
      its replacement by oily fluids, in several cases, the anisotropic effect of the
      euplantula disappeared due to the decrease of friction forces in push-direction.
      In the euplantulae, adhesion was one to two orders of magnitude lower than
      friction. Whereas the tenacity was slightly decreased with depleted secretion, it
      was considerably increased after artificial application of oily liquids. In terms
      of adhesion, it is concluded that the semi-solid consistence of the natural
      adhesion-mediating secretion facilitates the detachment of the tarsus during
      locomotion. In terms of friction, on smooth to nanorough surfaces, the insects
      appear to benefit from employing emulsions instead of pure oils to avoid
      excessive friction forces, whereas on rougher surfaces the tarsal fluid rather
      functions in improving surface contact by keeping the cuticle compliable and
      compensating surface asperities of the substratum.

PMID- 28507056
TI  - Parallel in vivo monitoring of pH in gill capillaries and muscles of fishes using
      microencapsulated biomarkers.
AB  - Tracking physiological parameters in different organs within the same organism
      simultaneously and in real time can provide an outstanding representation of the
      organism's physiological status. The state-of-the-art technique of using
      encapsulated fluorescent molecular probes (microencapsulated biomarkers) is a
      unique tool that can serve as a platform for the development of new methods to
      obtain in vivo physiological measurements and is applicable to a broad range of
      organisms. Here, we describe a novel technique to monitor the pH of blood inside
      the gill capillaries and interstitial fluid of muscles by using microencapsulated
      biomarkers in a zebrafish model. The functionality of the proposed technique is
      shown by the identification of acidification under anesthesia-induced coma and
      after death. The pH in muscles reacts to hypoxia faster than that in the gill
      bloodstream, which makes both parameters applicable as markers of either local or
      bodily reactions.

PMID- 28507054
TI  - Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in
      Prostate Cancer.
AB  - Despite the known importance of androgen receptor (AR) signaling in prostate
      cancer, the processes downstream of AR that drive disease development and
      progression remain poorly understood. This knowledge gap has thus limited the
      ability to treat cancer. Here, it is demonstrated that androgens increase the
      metabolism of glutamine in prostate cancer cells. This metabolism was required
      for maximal cell growth under conditions of serum starvation. Mechanistically, AR
      signaling promoted glutamine metabolism by increasing the expression of the
      glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in
      prostate cancer. Correspondingly, gene expression signatures of AR activity
      correlated with SLC1A4 and SLC1A5 mRNA levels in clinical cohorts. Interestingly,
      MYC, a canonical oncogene in prostate cancer and previously described master
      regulator of glutamine metabolism, was only a context-dependent regulator of
      SLC1A4 and SLC1A5 levels, being unable to regulate either transporter in PTEN
      wild-type cells. In contrast, rapamycin was able to decrease the androgen
      mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating
      that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake
      and prostate cancer cell growth. Taken together, these data indicate that three
      well-established oncogenic drivers (AR, MYC, and mTOR) function by converging to
      collectively increase the expression of glutamine transporters, thereby promoting
      glutamine uptake and subsequent prostate cancer cell growth.Implications: AR,
      MYC, and mTOR converge to increase glutamine uptake and metabolism in prostate
      cancer through increasing the levels of glutamine transporters. Mol Cancer Res;
      15(8); 1017-28. (c)2017 AACR.

PMID- 28507057
TI  - Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function.
AB  - Efficacy of statin-based therapies in reducing cardiovascular mortality in
      individuals with CKD seems to diminish as eGFR declines. The strongest evidence
      supporting the cardiovascular benefit of statins in individuals with CKD was
      shown with ezetimibe plus simvastatin versus placebo. However, whether
      combination therapy or statin alone resulted in cardiovascular benefit is
      uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT
      (ezetimibe plus simvastatin versus simvastatin alone in individuals with
      cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc
      the relationship of eGFR with end points across treatment arms. For the primary
      end point of cardiovascular death, major coronary event, or nonfatal stroke, the
      relative risk reduction of combination therapy compared with monotherapy differed
      by eGFR (P=0.04). The difference in treatment effect was observed at eGFR<=75
      ml/min per 1.73 m2 and most apparent at levels <=60 ml/min per 1.73 m2 Compared
      with individuals receiving monotherapy, individuals receiving combination therapy
      with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction
      (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those
      with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87;
      95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary
      syndrome, combination therapy seemed to be more effective than monotherapy in
      individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further
      studies examining potential benefits of combination lipid-lowering therapy in
      individuals with CKD are needed.

PMID- 28507058
TI  - Hepatocyte Nuclear Factor-1beta Regulates Urinary Concentration and Response to
      Hypertonicity.
AB  - The transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) is essential
      for normal kidney development and function. Inactivation of HNF-1beta in mouse
      kidney tubules leads to early-onset cyst formation and postnatal lethality. Here,
      we used Pkhd1/Cre mice to delete HNF-1beta specifically in renal collecting ducts
      (CDs). CD-specific HNF-1beta mutant mice survived long term and developed slowly
      progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared
      with wild-type littermates, HNF-1beta mutant mice exhibited polyuria and
      polydipsia. Before the development of significant renal structural abnormalities,
      mutant mice exhibited low urine osmolality at baseline and after water
      restriction and administration of desmopressin. However, mutant and wild-type
      mice had similar plasma vasopressin and solute excretion levels. HNF-1beta mutant
      kidneys showed increased expression of aquaporin-2 mRNA but mislocalized
      expression of aquaporin-2 protein in the cytoplasm of CD cells. Mutant kidneys
      also had decreased expression of the UT-A urea transporter and collectrin, which
      is involved in apical membrane vesicle trafficking. Treatment of HNF-1beta mutant
      mIMCD3 cells with hypertonic NaCl inhibited the induction of osmoregulated genes,
      including Nr1h4, which encodes the transcription factor FXR that is required for
      maximal urinary concentration. Chromatin immunoprecipitation and sequencing
      experiments revealed HNF-1beta binding to the Nr1h4 promoter in wild-type
      kidneys, and immunoblot analysis revealed downregulated expression of FXR in HNF
      1beta mutant kidneys. These findings reveal a novel role of HNF-1beta in
      osmoregulation and identify multiple mechanisms, whereby mutations of HNF-1beta
      produce defects in urinary concentration.

PMID- 28507059
TI  - Change in Physical Activity and Sitting Time After Myocardial Infarction and
      Mortality Among Postmenopausal Women in the Women's Health Initiative
      Observational Study.
AB  - BACKGROUND: How physical activity (PA) and sitting time may change after first
      myocardial infarction (MI) and the association with mortality in postmenopausal
      women is unknown. METHODS AND RESULTS: Participants included postmenopausal women
      in the Women's Health Initiative-Observational Study, aged 50 to 79 years who
      experienced a clinical MI during the study. This analysis included 856 women who
      had adequate data on PA exposure and 533 women for sitting time exposures.
      Sitting time was self-reported at baseline, year 3, and year 6. Self-reported PA
      was reported at baseline through year 8. Change in PA and sitting time were
      calculated as the difference between the cumulative average immediately following
      MI and the cumulative average immediately preceding MI. The 4 categories of
      change were: maintained low, decreased, increased, and maintained high. The cut
      points were >=7.5 metabolic equivalent of task hours/week versus <7.5 metabolic
      equivalent of task hours/week for PA and >=8 h/day versus <8 h/day for sitting
      time. Cox proportional hazard models estimated hazard ratios and 95% CIs for all
      cause, coronary heart disease, and cardiovascular disease mortality. Compared
      with women who maintained low PA (referent), the risk of all-cause mortality was:
      0.54 (0.34-0.86) for increased PA and 0.52 (0.36-0.73) for maintained high PA.
      Women who had pre-MI levels of sitting time <8 h/day, every 1 h/day increase in
      sitting time was associated with a 9% increased risk (hazard ratio=1.09, 95% CI:
      1.01, 1.19) of all-cause mortality. CONCLUSIONS: Meeting the recommended PA
      guidelines pre- and post-MI may have a protective role against mortality in
      postmenopausal women.

PMID- 28507060
TI  - Alogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Alleviates Atrial Remodeling and
      Improves Mitochondrial Function and Biogenesis in Diabetic Rabbits.
AB  - BACKGROUND: There is increasing evidence implicating atrial mitochondrial
      dysfunction in the pathogenesis of atrial fibrillation. In this study, we
      explored whether alogliptin, a dipeptidyl peptidase-4 inhibitor, can prevent
      mitochondrial dysfunction and atrial remodeling in a diabetic rabbit model.
      METHODS AND RESULTS: A total of 90 rabbits were randomized into 3 groups as
      follows: control group (n=30), alloxan-induced diabetes mellitus group (n=30),
      and alogliptin-treated (12.5 mg/kg per day for 8 weeks) diabetes mellitus group
      (n=30). Echocardiographic and hemodynamic assessments were performed in vivo. The
      serum concentrations of glucagon-like peptide-1, insulin, and inflammatory and
      oxidative stress markers were measured. Electrophysiological properties of
      Langendorff-perfused rabbit hearts were assessed. Mitochondrial morphology,
      respiratory function, membrane potential, and reactive oxygen species generation
      rate were assessed. The protein expression of transforming growth factor beta1,
      nuclear factor kappaB p65, and mitochondrial biogenesis-related proteins were
      measured by Western blot analysis. Diabetic rabbits exhibited left ventricular
      hypertrophy and left atrial dilation without obvious hemodynamic abnormalities,
      and all of these changes were attenuated by alogliptin. Compared with the control
      group, higher atrial fibrillation inducibility in the diabetes mellitus group was
      observed, and markedly reduced by alogliptin. Alogliptin decreased mitochondrial
      reactive oxygen species production rate, prevented mitochondrial membrane
      depolarization, and alleviated mitochondrial swelling in diabetic rabbits. It
      also improved mitochondrial biogenesis by peroxisome proliferator-activated
      receptor-gamma coactivator 1alpha/nuclear respiratory factor-1/mitochondrial
      transcription factor A signaling regulated by adiponectin/AMP-activated protein
      kinase. CONCLUSIONS: Dipeptidyl peptidase-4 inhibitors can prevent atrial
      fibrillation by reversing electrophysiological abnormalities, improving
      mitochondrial function, and promoting mitochondrial biogenesis.

PMID- 28507061
TI  - RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and
      tumorigenesis.
AB  - Disassembly of nucleosomes in which genomic DNA is packaged with histone
      regulates gene expression. However, the mechanisms underlying nucleosome
      disassembly for gene expression remain elusive. We show here that epidermal
      growth factor receptor activation results in the binding of the RNF8 forkhead
      associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to
      K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome
      dependent protein degradation. In addition, H3 polyubiquitylation induces histone
      dissociation from chromatin, nucleosome disassembly, and binding of RNA
      polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated
      histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation
      and brain tumorigenesis. Our findings uncover the role of RNF8-mediated histone
      H3 polyubiquitylation in the regulation of histone H3 stability and chromatin
      modification, paving the way to gene expression regulation and tumorigenesis.

PMID- 28507062
TI  - Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to
      intestinal helminths.
AB  - Immunity to intestinal helminth infections requires the rapid activation of T
      helper 2 cells (Th2 cells). However, simultaneous expansion of CD4+Foxp3+
      regulatory T cells (T reg cells) impedes protective responses, resulting in
      chronic infections. The ratio between T reg and effector T cells can therefore
      determine the outcome of infection. The redifferentiation of T reg cells into Th
      cells has been identified in hyperinflammatory diseases. In this study, we asked
      whether ex-T reg Th2 cells develop and contribute to type-2 immunity. Using
      multigene reporter and fate-reporter systems, we demonstrate that a significant
      proportion of Th2 cells derive from Foxp3+ cells after Heligmosomoides polygyrus
      infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2
      effector functions and provide immunity to H. polygyrus Through selective
      deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for
      the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that
      converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and
      limit T reg cell-mediated suppression.

PMID- 28507064
TI  - Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Mediates
      Ubiquitination-Dependent STAT3 Activation upon Salmonella enterica Serovar
      Typhimurium Infection.
AB  - Salmonella enterica serovar Typhimurium can inject effector proteins into host
      cells via type III secretion systems (T3SSs). These effector proteins modulate a
      variety of host transcriptional responses to facilitate bacterial growth and
      survival. Here we show that infection of host cells with S Typhimurium
      specifically induces the ubiquitination of tumor necrosis factor receptor
      associated factor 6 (TRAF6). This TRAF6 ubiquitination is triggered by the
      Salmonella pathogenicity island 1 (SPI-1) T3SS effectors SopB and SopE2. We also
      demonstrate that TRAF6 is involved in the SopB/SopE2-induced phosphorylation of
      signal transducer and activator of transcription 3 (STAT3), a signaling event
      conducive to the intracellular growth of S Typhimurium. Specifically, TRAF6
      mediates lysine-63 ubiquitination within the Src homology 2 (SH2) domain of
      STAT3, which is an essential step for STAT3 membrane recruitment and subsequent
      phosphorylation in response to S Typhimurium infection. TRAF6 ubiquitination
      participates in STAT3 phosphorylation rather than serving as only a hallmark of
      E3 ubiquitin ligase activation. Our results reveal a novel strategy in which S
      Typhimurium T3SS effectors broaden their functions through the activation of host
      proteins in a ubiquitination-dependent manner to manipulate host cells into
      becoming a Salmonella-friendly zone.

PMID- 28507063
TI  - The Mycobacterium tuberculosis MmpL11 Cell Wall Lipid Transporter Is Important
      for Biofilm Formation, Intracellular Growth, and Nonreplicating Persistence.
AB  - The mycobacterial cell wall is crucial to the host-pathogen interface, because it
      provides a barrier against antibiotics and the host immune response. In addition,
      cell wall lipids are mycobacterial virulence factors. The mycobacterial membrane
      protein large (MmpL) proteins are cell wall lipid transporters that are important
      for basic mycobacterial physiology and Mycobacterium tuberculosis pathogenesis.
      MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria,
      a feature consistent with an important role in the basic physiology of the
      bacterium. MmpL3 is essential and transports trehalose monomycolate to the
      mycobacterial surface. In this report, we characterize the role of MmpL11 in M.
      tuberculosis. M. tuberculosismmpL11 mutants have altered biofilms associated with
      lower levels of mycolic acid wax ester and long-chain triacylglycerols than those
      for wild-type bacteria. While the growth rate of the mmpL11 mutant is similar to
      that of wild-type M. tuberculosis in macrophages, the mutant exhibits impaired
      survival in an in vitro granuloma model. Finally, we show that the survival or
      recovery of the mmpL11 mutant is impaired when it is incubated under conditions
      of nutrient and oxygen starvation. Our results suggest that MmpL11 and its cell
      wall lipid substrates are important for survival in the context of adaptive
      immune pressure and for nonreplicating persistence, both of which are critically
      important aspects of M. tuberculosis pathogenicity.

PMID- 28507065
TI  - Mutations in the beta-Subunit of the RNA Polymerase Impair the Surface-Associated
      Motility and Virulence of Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a major cause of antibiotic-resistant nosocomial
      infections worldwide. In this study, several rifampin-resistant spontaneous
      mutants obtained from the A. baumannii ATCC 17978 strain that differed in their
      point mutations in the rpoB gene, encoding the beta-subunit of the RNA
      polymerase, were isolated. All the mutants harboring amino acid substitutions in
      position 522 or 540 of the RpoB protein were impaired in surface-associated
      motility and had attenuated virulence in the fertility model of Caenorhabditis
      elegans The transcriptional profile of these mutants included six downregulated
      genes encoding proteins homologous to transporters and metabolic enzymes
      widespread among A. baumannii clinical isolates. The construction of knockout
      mutants in each of the six downregulated genes revealed a significant reduction
      in the surface-associated motility and virulence of four of them in the A.
      baumannii ATCC 17978 strain, as well as in the virulent clinical isolate MAR002.
      Taken together, our results provide strong evidence of the connection between
      motility and virulence in this multiresistant nosocomial pathogen.

PMID- 28507066
TI  - Microbiomes of Site-Specific Dental Plaques from Children with Different Caries
      Status.
AB  - The oral microbiota associated with the initiation and progression of dental
      caries has yet to be fully characterized. The Human Oral Microbe Identification
      Using Next-Generation Sequencing (HOMINGS) approach was used to analyze the
      microbiomes of site-specific supragingival dental plaques from children with
      different caries status. Fifty-five children (2 to 7 years of age) were assessed
      at baseline and at 12 months and grouped as caries free (CF), caries active with
      enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque
      samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE)
      and dentin carious lesions (PD) were collected. 16S community profiles were
      obtained by HOMINGS, and 408 bacterial species and 84 genus probes were assigned.
      Plaque bacterial communities showed temporal stability, as there was no
      significant difference in beta diversity values between the baseline and 12-month
      samples. Irrespective of collection time points, the microbiomes of healthy tooth
      surfaces differed substantially from those found during caries activity. All
      pairwise comparisons of beta diversity values between groups were significantly
      different (P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE
      groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most
      frequently detected taxa across the plaque groups, followed by Streptococcus
      sanguinis, which was highly abundant in CF-PF. Well-known acidogenic/aciduric
      species such as Streptococcus mutans, Scardovia wiggsiae, Parascardovia
      denticolens, and Lactobacillus salivarius were found almost exclusively in CA-PD.
      The microbiomes of supragingival dental plaque differ substantially among tooth
      surfaces and children of different caries activities. In support of the
      ecological nature of caries etiology, a steady transition in community species
      composition was observed with disease progression.

PMID- 28507069
TI  - SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative
      Biofilm Formation in Staphylococcus aureus.
AB  - Biofilms are multicellular communities of microorganisms living as a quorum
      rather than as individual cells. The bacterial human pathogen Staphylococcus
      aureus uses oxygen as a terminal electron acceptor during respiration. Infected
      human tissues are hypoxic or anoxic. We recently reported that impaired
      respiration elicits a programmed cell lysis (PCL) phenomenon in S. aureus leading
      to the release of cellular polymers that are utilized to form biofilms. PCL is
      dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB
      two-component regulatory system (TCRS). In the current study, we report that the
      SaeRS TCRS also governs fermentative biofilm formation by positively influencing
      AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA)
      also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent
      biofilm formation occurred in response to changes in cellular respiratory status.
      Genetic evidence presented suggests that a high cellular titer of phosphorylated
      SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and
      SrrAB influence biofilm formation independently of one another. Analyses using a
      mouse model of orthopedic implant-associated biofilm formation found that both
      SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the
      dominant system driving biofilm formation in vivo We propose a model wherein
      impaired cellular respiration stimulates SaeRS via an as yet undefined signal
      molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm
      formation.

PMID- 28507067
TI  - Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in
      the Control of Virulence Traits in Chromobacterium violaceum.
AB  - A major pathway for the detoxification of organic hydroperoxides, such as cumene
      hydroperoxide (CHP), involves the MarR family transcriptional regulator OhrR and
      the peroxidase OhrA. However, the effect of these peroxides on the global
      transcriptome and the contribution of the OhrA/OhrR system to bacterial virulence
      remain poorly explored. Here, we analyzed the transcriptome profiles of
      Chromobacterium violaceum exposed to CHP and after the deletion of ohrR, and we
      show that OhrR controls the virulence of this human opportunistic pathogen. DNA
      microarray and Northern blot analyses of CHP-treated cells revealed the
      upregulation of genes related to the detoxification of peroxides (antioxidant
      enzymes and thiol-reducing systems), the degradation of the aromatic moiety of
      CHP (oxygenases), and protection against other secondary stresses (DNA repair,
      heat shock, iron limitation, and nitrogen starvation responses). Furthermore, we
      identified two upregulated genes (ohrA and a putative diguanylate cyclase with a
      GGDEF domain for cyclic di-GMP [c-di-GMP] synthesis) and three downregulated
      genes (hemolysin, chitinase, and collagenase) in the ohrR mutant by transcriptome
      analysis. Importantly, we show that OhrR directly repressed the expression of the
      putative diguanylate cyclase. Using a mouse infection model, we demonstrate that
      the ohrR mutant was attenuated for virulence and showed a decreased bacterial
      burden in the liver. Moreover, an ohrR-diguanylate cyclase double mutant
      displayed the same virulence as the wild-type strain. In conclusion, we have
      defined the transcriptional response to CHP, identified potential virulence
      factors such as diguanylate cyclase as members of the OhrR regulon, and shown
      that C. violaceum uses the transcriptional regulator OhrR to modulate its
      virulence.

PMID- 28507068
TI  - Genome-Wide Survey of Pseudomonas aeruginosa PA14 Reveals a Role for the
      Glyoxylate Pathway and Extracellular Proteases in the Utilization of Mucin.
AB  - Chronic airway infections by the opportunistic pathogen Pseudomonas aeruginosa
      are a major cause of mortality in cystic fibrosis (CF) patients. Although this
      bacterium has been extensively studied for its virulence determinants, biofilm
      growth, and immune evasion mechanisms, comparatively little is known about the
      nutrient sources that sustain its growth in vivo Respiratory mucins represent a
      potentially abundant bioavailable nutrient source, although we have recently
      shown that canonical pathogens inefficiently use these host glycoproteins as a
      growth substrate. However, given that P. aeruginosa, particularly in its biofilm
      mode of growth, is thought to grow slowly in vivo, the inefficient use of mucin
      glycoproteins may be relevant to its persistence within the CF airways. To this
      end, we used whole-genome fitness analysis, combining transposon mutagenesis with
      high-throughput sequencing, to identify genetic determinants required for P.
      aeruginosa growth using intact purified mucins as a sole carbon source. Our
      analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway
      and amino acid biosynthetic machinery are required for mucin utilization.
      Secondary analyses confirmed the simultaneous liberation and consumption of
      acetate during mucin degradation and revealed a central role for the
      extracellular proteases LasB and AprA. Together, these studies describe a
      molecular basis for mucin-based nutrient acquisition by P. aeruginosa and reveal
      a host-pathogen dynamic that may contribute to its persistence within the CF
      airways.

PMID- 28507070
TI  - Limited Colonization Undermined by Inadequate Early Immune Responses Defines the
      Dynamics of Decidual Listeriosis.
AB  - The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease
      in pregnant women, which can lead to preterm labor, stillbirth, or severe
      neonatal disease. Colonization of the maternal decidua appears to be an initial
      step in the maternal component of the disease as well as bacterial transmission
      to the placenta and fetus. Host-pathogen interactions in the decidua during this
      early stage of infection remain poorly understood. Here, we assessed the dynamics
      of L. monocytogenes infection in primary human decidual organ cultures and in the
      murine decidua in vivo A high inoculum was necessary to infect both human and
      mouse deciduas, and the data support the existence of a barrier to initial
      colonization of the murine decidua. If successful, however, colonization in both
      species was followed by significant bacterial expansion associated with an
      inability of the decidua to mount appropriate innate cellular immune responses.
      The innate immune deficits included the failure of bacterial foci to attract
      macrophages and NK cells, cell types known to be important for early defenses
      against L. monocytogenes in the spleen, as well as a decrease in the tissue
      density of inflammatory Ly6Chi monocytes in vivo These results suggest that the
      infectivity of the decidua is not the result of an enhanced recruitment of L.
      monocytogenes to the gestational uterus but rather is due to compromised local
      innate cellular immune responses.

PMID- 28507072
TI  - Recruitment of Neutrophils Mediated by Vgamma2 gammadelta T Cells Deteriorates
      Liver Fibrosis Induced by Schistosoma japonicum Infection in C57BL/6 Mice.
AB  - Conventional adaptive T cell responses contribute to the pathogenesis of
      Schistosoma japonicum infection, leading to liver fibrosis. However, the role of
      gamma-delta (gammadelta) T cells in this disease is less clear. gammadelta T
      cells are known to secrete interleukin-17 (IL-17) in response to infection,
      exerting either protective or pathogenic functions. In the present study, mice
      infected with S. japonicum are used to characterize the role of gammadelta T
      cells. Combined with the infection of S. japonicum, an extremely significant
      increase in the percentage of neutrophils in the CD45+ cells was detected (from
      approximately 2.45% to 46.10% in blood and from 0.18% to 7.34% in spleen).
      Further analysis identified two different gammadelta T cell subsets that have
      different functions in the formation of granulomas in S. japonicum-infected mice.
      The Vgamma1 T cells secrete gamma interferon (IFN-gamma) only, while the Vgamma2
      T cells secrete both IL-17A and IFN-gamma. Both subtypes lose the ability to
      secrete cytokine during the late stage of infection (12 weeks postinfection).
      When we depleted the Vgamma2 T cells in infected mice, the percentage of
      neutrophils in blood and spleen decreased significantly, the liver fibrosis in
      the granulomas was reduced, and the level of IL-17A in the serum decreased (P <
      0.05). These results suggest that during S. japonicum infection, Vgamma2 T cells
      can recruit neutrophils and aggravate liver fibrosis by secreting IL-17A. This is
      the first report that a subset of gammadelta T cells plays a partial role in the
      pathological process of schistosome infection.

PMID- 28507074
TI  - British Thoracic Society Oxygen Guidelines: another clinical brick in the wall.

PMID- 28507071
TI  - Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by
      Leishmania major via the Exosome Pathway.
AB  - Similar to other intracellular pathogens, Leishmania parasites are known to evade
      the antimicrobial effector functions of host immune cells. To date, however, only
      a few virulence factors have been described for Leishmania major, one of the
      causative agents of cutaneous leishmaniasis. Here, we have characterized the
      expression and function of an L. major phosphatase, which we termed LmPRL-1. This
      enzyme shows a strong structural similarity to the human phosphatases of
      regenerating liver (PRL-1, -2, and -3) that regulate the proliferation,
      differentiation, and motility of cells. The biochemical characterization of the
      L. major phosphatase revealed that the enzyme is redox sensitive. When analyzing
      the subcellular localization of LmPRL-1 in promastigotes, amastigotes, and
      infected macrophages, we found that the phosphatase was predominantly expressed
      and secreted by promastigotes via the exosome route. Finally, we observed that
      ectopic expression of LmPRL-1 in L. major led to an increased number of parasites
      in macrophages. From these data, we conclude that the L. major phosphatase LmPRL
      1 contributes to the intracellular survival of the parasites in macrophages.

PMID- 28507077
TI  - Correction.

PMID- 28507075
TI  - Metalworking fluids: a new cause of occupational non-asthmatic eosinophilic
      bronchitis.

PMID- 28507073
TI  - Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against
      Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei.
AB  - Burkholderia mallei, a facultative intracellular bacterium and tier 1 biothreat,
      causes the fatal zoonotic disease glanders. The organism possesses multiple genes
      encoding autotransporter proteins, which represent important virulence factors
      and targets for developing countermeasures in pathogenic Gram-negative bacteria.
      In the present study, we investigated one of these autotransporters, BatA, and
      demonstrate that it displays lipolytic activity, aids in intracellular survival,
      is expressed in vivo, elicits production of antibodies during infection, and
      contributes to pathogenicity in a mouse aerosol challenge model. A mutation in
      the batA gene of wild-type strain ATCC 23344 was found to be particularly
      attenuating, as BALB/c mice infected with the equivalent of 80 median lethal
      doses cleared the organism. This finding prompted us to test the hypothesis that
      vaccination with the batA mutant strain elicits protective immunity against
      subsequent infection with wild-type bacteria. We discovered that not only does
      vaccination provide high levels of protection against lethal aerosol challenge
      with B. mallei ATCC 23344, it also protects against infection with multiple
      isolates of the closely related organism and causative agent of melioidosis,
      Burkholderia pseudomallei Passive-transfer experiments also revealed that the
      protective immunity afforded by vaccination with the batA mutant strain is
      predominantly mediated by IgG antibodies binding to antigens expressed
      exclusively in vivo Collectively, our data demonstrate that BatA is a target for
      developing medical countermeasures and that vaccination with a mutant lacking
      expression of the protein provides a platform to gain insights regarding
      mechanisms of protective immunity against B. mallei and B. pseudomallei,
      including antigen discovery.

PMID- 28507079
TI  - Distance constraints on activation of TRPV4 channels by AKAP150-bound PKCalpha in
      arterial myocytes.
AB  - TRPV4 (transient receptor potential vanilloid 4) channels are Ca2+-permeable
      channels that play a key role in regulating vascular tone. In arterial myocytes,
      opening of TRPV4 channels creates local increases in Ca2+ influx, detectable
      optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the
      action of the vasoconstrictor angiotensin II (AngII). This modulation depends on
      the activation of subcellular signaling domains that comprise protein kinase C
      alpha (PKCalpha) bound to the anchoring protein AKAP150. Here, we used super
      resolution nanoscopy, patch-clamp electrophysiology, Ca2+ imaging, and
      mathematical modeling approaches to test the hypothesis that AKAP150-dependent
      modulation of TRPV4 channels is critically dependent on the distance between
      these two proteins in the sarcolemma of arterial myocytes. Our data show that the
      distance between AKAP150 and TRPV4 channel clusters varies with sex and arterial
      bed. Consistent with our hypothesis, we further find that basal and AngII-induced
      TRPV4 channel activity decays exponentially as the distance between TRPV4 and
      AKAP150 increases. Our data suggest a maximum radius of action of ~200 nm for
      local modulation of TRPV4 channels by AKAP150-associated PKCalpha.

PMID- 28507081
TI  - Reversion of anergy signatures in clonal CD21low B cells of mixed
      cryoglobulinemia after clearance of HCV viremia.
AB  - Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal
      expansion of IgM+CD27+ B cells. These cells display both the features of anergy
      induced by continual engagement of the B-cell receptor (BCR), such as high
      expression of phosphorylated extracellular signal-regulated kinase (pERK) and
      reduced lifespan, and of virus-specific exhaustion, such as CD21low phenotype and
      a defective response to ligation of BCR and Toll-like receptor 9 (TLR9). MC
      usually regresses after eradication of HCV with interferon, whose
      immunomodulatory activity might contribute to this effect. We investigated the
      phenotypic and functional changes in clonal B cells of MC patients with sustained
      virologic responses to direct-acting antivirals (DAAs), which lack
      immunomodulatory properties. We found that high pERK expression and accelerated
      apoptosis revert within 4 weeks after beginning therapy, whereas clonal B cells
      unresponsive to TLR9 stimulation persist for at least 24 weeks, although they may
      partially rescue normal CD21 expression. Thus, similar to mouse models, features
      of anergy in MC B cells rapidly revert after disengagement from HCV, whereas
      virus-specific exhaustion imparts a durable inhibitory imprint on cell function.
      Treatment of HCV+ MC with DAAs provides a valuable tool for untangling the
      molecular mechanisms of anergy and exhaustion in human B cells.

PMID- 28507080
TI  - Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors.
AB  - Ionotropic glutamate receptors (iGluRs), including AMPA receptor (AMPAR) and NMDA
      receptor (NMDAR) subtypes, are ligand-gated ion channels that mediate signaling
      at the majority of excitatory synapses in the nervous system. The iGluR pore
      domain is structurally and evolutionarily related to an inverted two
      transmembrane K+ channel. Peripheral to the pore domain in eukaryotic iGluRs is
      an additional transmembrane helix, the M4 segment, which interacts with the pore
      domain of a neighboring subunit. In AMPARs, the integrity of the alignment of a
      specific face of M4 with the adjacent pore domain is essential for receptor
      oligomerization. In contrast to AMPARs, NMDARs are obligate heterotetramers
      composed of two GluN1 and typically two GluN2 subunits. Here, to address the
      function of the M4 segments in NMDARs, we carry out a tryptophan scan of M4 in
      GluN1 and GluN2A subunits. Unlike AMPARs, the M4 segments in NMDAR subunits makes
      only a limited contribution to their biogenesis. However, the M4 segments in both
      NMDAR subunits are critical for receptor activation, with mutations at some
      positions, most notably at the extreme extracellular end, completely halting the
      gating process. Furthermore, although the AMPAR M4 makes a minimal contribution
      to receptor desensitization, the NMDAR M4 segments have robust and subunit
      specific effects on desensitization. These findings reveal that the functional
      roles of the M4 segments in AMPARs and NMDARs have diverged in the course of
      their evolution and that the M4 segments in NMDARs may act as a transduction
      pathway for receptor modulation at synapses.

PMID- 28507084
TI  - Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.

PMID- 28507085
TI  - Endothelial basement membrane laminin 511 is essential for shear stress response.

PMID- 28507082
TI  - Association between diffuse myocardial fibrosis and diastolic dysfunction in
      sickle cell anemia.
AB  - Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic
      dysfunction and hyperdynamic features. Diastolic dysfunction portends early
      mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial
      fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA
      is unknown. We used cardiac magnetic resonance measurements of extracellular
      volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25
      individuals with SCA (mean age, 23 +/- 13 years) and determine the association
      between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated
      from pre- and post-gadolinium T1 measurements of blood and myocardium, and
      diastolic function was assessed by echocardiography. ECV was markedly increased
      in all participants compared with controls (0.44 +/- 0.08 vs 0.26 +/- 0.02, P <
      .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen
      patients (71%) had diastolic abnormalities, and 7 patients (29%) met the
      definition of diastolic dysfunction. Participants with diastolic dysfunction had
      higher ECV (0.49 +/- 0.07 vs 0.37 +/- 0.04, P = .01) and N-terminal pro-brain
      natriuretic peptide (NT-proBNP; 191 +/- 261 vs 33 +/- 33 pg/mL, P = .04) but
      lower hemoglobin (8.4 +/- 0.3 vs 10.9 +/- 1.4 g/dL, P = .004) compared with
      participants with normal diastolic function. Participants with the highest ECV
      values (>=0.40) were more likely to have diastolic dysfunction (P = .003) and
      increased left atrial volume (57 +/- 11 vs 46 +/- 12 mL/m2, P = .04) compared
      with those with ECV <0.4. ECV correlated with hemoglobin (r = -0.46, P = .03) and
      NT-proBNP (r = 0.62, P = .001). In conclusion, diffuse myocardial fibrosis,
      determined by ECV, is a common and previously underappreciated feature of SCA
      that is associated with diastolic dysfunction, anemia, and high NT-proBNP.
      Diffuse myocardial fibrosis is a novel mechanism that appears to underlie
      diastolic dysfunction in SCA.

PMID- 28507083
TI  - Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in
      acquired and congenital hemophilia A.
AB  - Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies
      (inhibitors) in patients with acquired hemophilia A (AHA) and congenital
      hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study,
      the frequency and epitope specificity of anti-C1 antibodies were analyzed in
      acquired and congenital hemophilia inhibitor patients (n = 178). The domain
      specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with
      single human domain human/porcine fVIII proteins and antibody binding to human
      A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins.
      The analysis with HSA-fVIII domain proteins confirmed the results of the HSM
      approach but resulted in higher detection levels. The higher detection levels
      with HSA-fVIII domain proteins are a result of antibody cross-reactivity with
      human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-,
      and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with
      AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63).
      Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed
      overlapping epitopes with murine C1-specific group A mAbs including 2A9.
      Mutational analyses identified distinct crucial binding residues for LE2E9
      (E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in
      patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies
      was particularly observed in patients with AHA. Overall, our study demonstrates
      that the C1 domain, in addition to the A2 and C2 domains, contributes
      significantly to the humoral anti-fVIII immune response in acquired and
      congenital hemophilia inhibitor patients.

PMID- 28507086
TI  - The role and impact of cost-sharing mechanisms for prescription drug coverage.

PMID- 28507088
TI  - Impact of income-based deductibles on drug use and health care utilization among
      older adults.
AB  - BACKGROUND: Income-based deductibles are present in several provincial public
      drug plans in Canada and have been the subject of extensive debate. We studied
      the impact of such deductibles in British Columbia's Fair PharmaCare plan on drug
      and health care utilization among older adults. METHODS: We used a quasi
      experimental regression discontinuity design to compare the impact of deductibles
      in BC's PharmaCare plan between older community-dwelling adults registered for
      the plan who were born in 1928 through 1939 (no deductible) and those born in
      1940 through 1951 (deductible equivalent to 2% of household income). We used 1.2
      million person-years of data between 2003 and 2015 to study public drug plan
      expenditures, overall drug use, and physician and hospital resource utilization
      in these 2 groups. RESULTS: The income-based deductible led to a 28.6% decrease
      in person-years in which public drug plan benefits were received (95% confidence
      interval [CI] -29.7% to -27.5%) and to a reduction in the per capita extent of
      annual benefits by $205.59 (95% CI -$247.81 to -$163.37). Despite this difference
      in public subsidy, we found no difference in the number of drugs received or in
      total drug spending once privately paid amounts were accounted for (p = 0.4 and
      0.8, respectively). Further, we found only small or nonexistent changes in health
      care resource utilization at the 1939 threshold. INTERPRETATION: A modest income
      based deductible had a considerable impact on the extent of public subsidy for
      prescription drugs. However, it had only a trivial impact on overall access to
      medicines and use of other health services. Unlike copayments, modest income
      based deductibles may safely reduce public spending on drugs for some population
      groups.

PMID- 28507089
TI  - Atypical pneumonia due to human bocavirus in an immunocompromised patient.

PMID- 28507090
TI  - Ocular surface squamous neoplasia in a patient with AIDS.

PMID- 28507087
TI  - Influence of environmental temperature on risk of gestational diabetes.
AB  - BACKGROUND: Cold-induced thermogenesis is known to improve insulin sensitivity,
      which may become increasingly relevant in the face of global warming. The aim of
      this study was to examine the relation between outdoor air temperature and the
      risk of gestational diabetes mellitus. METHODS: We identified all births in the
      Greater Toronto Area from 2002 to 2014 using administrative health databases.
      Generalized estimating equations were used to examine the relation between the
      mean 30-day outdoor air temperature before the time of gestational diabetes
      mellitus screening and the likelihood of diagnosis of gestational diabetes
      mellitus based on a validated algorithm using hospital records and physician
      service claims. RESULTS: Over the 12-year period, there were 555 911 births among
      396 828 women. Prevalence of gestational diabetes mellitus was 4.6% among women
      exposed to extremely cold mean outdoor air temperatures (<= -10 degrees C) in the
      30-day period before screening and increased to 7.7% among those exposed to hot
      mean 30-day temperatures (>= 24 degrees C). Each 10 degrees C increase in mean 30
      day temperature was associated with a 1.06 (95% confidence interval [CI] 1.04
      1.07) times higher odds of gestational diabetes mellitus, after adjusting for
      maternal age, parity, neighbourhood income quintile, world region and year. A
      similar effect was seen for each 10 degrees C rise in outdoor air temperature
      difference between 2 consecutive pregnancies for the same woman (adjusted odds
      ratio 1.06, 95% CI 1.03-1.08). INTERPRETATION: In our setting, there was a direct
      relation between outdoor air temperature and the likelihood of gestational
      diabetes mellitus. Future climate patterns may substantially affect global
      variations in the prevalence of diabetes, which also has important implications
      for the prevention and treatment of gestational diabetes mellitus.

PMID- 28507091
TI  - Liam Durcan: neurological narrative.

PMID- 28507092
TI  - List of essential medicines for Canada.

PMID- 28507093
TI  - A priority-setting framework is needed to understand the value of investing in a
      universal drug plan.

PMID- 28507094
TI  - CIHR announces winners of health research awards.

PMID- 28507095
TI  - Reducing inappropriate prescribing easier said than done.

PMID- 28507096
TI  - Back to the Future in Alberta.

PMID- 28507098
TI  - Cargo engagement protects protease adaptors from degradation in a substrate
      specific manner.
AB  - Protein degradation in bacteria is a highly controlled process involving
      proteolytic adaptors that regulate protein degradation during cell cycle
      progression or during stress responses. Many adaptors work as scaffolds that
      selectively bind cargo and tether substrates to their cognate proteases to
      promote substrate destruction, whereas others primarily activate the target
      protease. Because adaptors must bind their cognate protease, all adaptors run the
      risk of being recognized by the protease as substrates themselves, a process that
      could limit their effectiveness. Here we use purified proteins in a reconstituted
      system and in vivo studies to show that adaptors of the ClpXP protease are
      readily degraded but that cargo binding inhibits this degradation. We found that
      this principle extends across several adaptor systems, including the hierarchical
      adaptors that drive the Caulobacter bacterial cell cycle and the quality control
      adaptor SspB. We also found that the ability of a cargo to protect its adaptor is
      adaptor substrate-specific, as adaptors with artificial degradation tags were not
      protected even though cargo binding is unaffected. Our work points to an
      optimization of inherent adaptor degradation and cargo binding that ensures that
      robust adaptor activity is maintained when high amounts of substrate must be
      delivered and that adaptors can be eliminated when their tasks have been
      completed.

PMID- 28507097
TI  - Gene duplication and neo-functionalization in the evolutionary and functional
      divergence of the metazoan copper transporters Ctr1 and Ctr2.
AB  - Copper is an essential element for proper organismal development and is involved
      in a range of processes, including oxidative phosphorylation, neuropeptide
      biogenesis, and connective tissue maturation. The copper transporter (Ctr) family
      of integral membrane proteins is ubiquitously found in eukaryotes and mediates
      the high-affinity transport of Cu+ across both the plasma membrane and
      endomembranes. Although mammalian Ctr1 functions as a Cu+ transporter for Cu
      acquisition and is essential for embryonic development, a homologous protein,
      Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal
      Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary
      relationship to Ctr1 is unclear. Here we report a biochemical, genetic, and
      phylogenetic comparison of metazoan Ctr1 and Ctr2, suggesting that Ctr2 arose
      over 550 million years ago as a result of a gene duplication event followed by
      loss of Cu+ transport activity. Using a random mutagenesis and growth selection
      approach, we identified amino acid substitutions in human and mouse Ctr2 proteins
      that support copper-dependent growth in yeast and enhance copper accumulation in
      Ctr1-/- mouse embryonic fibroblasts. These mutations revert Ctr2 to a more
      ancestral Ctr1-like state while maintaining endogenous functions, such as
      stimulating Ctr1 cleavage. We suggest key structural aspects of metazoan Ctr1 and
      Ctr2 that discriminate between their biological roles, providing mechanistic
      insights into the evolutionary, biochemical, and functional relationships between
      these two related proteins.

PMID- 28507099
TI  - Carbon dioxide-dependent regulation of NF-kappaB family members RelB and p100
      gives molecular insight into CO2-dependent immune regulation.
AB  - CO2 is a physiological gas normally produced in the body during aerobic
      respiration. Hypercapnia (elevated blood pCO2 >~50 mm Hg) is a feature of several
      lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is
      associated with increased susceptibility to bacterial infections and suppression
      of inflammatory signaling. The NF-kappaB pathway has been implicated in these
      effects; however, the molecular mechanisms underpinning cellular sensitivity of
      the NF-kappaB pathway to CO2 are not fully elucidated. Here, we identify several
      novel CO2-dependent changes in the NF-kappaB pathway. NF-kappaB family members
      p100 and RelB translocate to the nucleus in response to CO2 A cohort of RelB
      protein-protein interactions (e.g. with Raf-1 and IkappaBalpha) are altered by
      CO2 exposure, although others are maintained (e.g. with p100). RelB is processed
      by CO2 in a manner dependent on a key C-terminal domain located in its
      transactivation domain. Loss of the RelB transactivation domain alters NF-kappaB
      dependent transcriptional activity, and loss of p100 alters sensitivity of RelB
      to CO2 Thus, we provide molecular insight into the CO2 sensitivity of the NF
      kappaB pathway and implicate altered RelB/p100-dependent signaling in the CO2
      dependent regulation of inflammatory signaling.

PMID- 28507100
TI  - The microRNA machinery regulates fasting-induced changes in gene expression and
      longevity in Caenorhabditis elegans.
AB  - Intermittent fasting (IF) is a dietary restriction regimen that extends the
      lifespans of Caenorhabditis elegans and mammals by inducing changes in gene
      expression. However, how IF induces these changes and promotes longevity remains
      unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs),
      small non-coding RNAs (~22 nucleotides) that repress gene expression and whose
      expression can be altered by fasting. To test this proposition, we examined the
      role of the miRNA machinery in fasting-induced transcriptional changes and
      longevity in C. elegans We revealed that fasting up-regulated the expression of
      the miRNA-induced silencing complex (miRISC) components, including Argonaute and
      GW182, and the miRNA-processing enzyme DRSH-1 (the ortholog of the Drosophila
      Drosha enzyme). Our lifespan measurements demonstrated that IF-induced longevity
      was suppressed by knock-out or knockdown of miRISC components and was completely
      inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting
      induced changes in the expression of the target genes of DAF-16, the insulin/IGF
      1 signaling effector in C. elegans Fasting-induced transcriptome alterations were
      substantially and modestly suppressed in the drsh-1 null mutant and the null
      mutant of ain-1, a gene encoding GW182, respectively. Moreover, miRNA array
      analyses revealed that the expression levels of numerous miRNAs changed after 2
      days of fasting. These results indicate that components of the miRNA machinery,
      especially the miRNA-processing enzyme DRSH-1, play an important role in
      mediating IF-induced longevity via the regulation of fasting-induced changes in
      gene expression.

PMID- 28507101
TI  - Human myosin VIIa is a very slow processive motor protein on various cellular
      actin structures.
AB  - Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human
      Usher syndrome (USH) type 1B, which causes human congenital hearing and visual
      loss. Although it has been thought that the role of human myosin VIIa is critical
      for USH1 protein tethering with actin and transportation along actin bundles in
      inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we
      studied the motor function of the tail-truncated human myosin VIIa dimer
      (HM7ADeltaTail/LZ) at the single-molecule level. We found that the
      HM7ADeltaTail/LZ moves processively on single actin filaments with a step size of
      35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4
      s, yielding ~0.3 s-1 for the mechanical turnover rate; hence, the velocity of
      HM7ADeltaTail/LZ was extremely slow, at 11 nm.s-1 We also examined
      HM7ADeltaTail/LZ movement on various actin structures in demembranated cells.
      HM7ADeltaTail/LZ showed unidirectional movement on actin structures at cell
      edges, such as lamellipodia and filopodia. However, HM7ADeltaTail/LZ frequently
      missed steps on actin tracks and exhibited bidirectional movement at stress
      fibers, which was not observed with tail-truncated myosin Va. These results
      suggest that the movement of the human myosin VIIa motor protein is more
      efficient on lamellipodial and filopodial actin tracks than on stress fibers,
      which are composed of actin filaments with different polarity, and that the actin
      structures influence the characteristics of cargo transportation by human myosin
      VIIa. In conclusion, myosin VIIa movement appears to be suitable for
      translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells.

PMID- 28507104
TI  - Genetic Characterization of Broad-Host-Range IncQ Plasmids Harboring blaVEB-18 in
      Vibrio Species.

PMID- 28507103
TI  - Nicotinic Acid Phosphoribosyltransferase Regulates Cancer Cell Metabolism,
      Susceptibility to NAMPT Inhibitors, and DNA Repair.
AB  - In the last decade, substantial efforts have been made to identify NAD+
      biosynthesis inhibitors, specifically against nicotinamide
      phosphoribosyltransferase (NAMPT), as preclinical studies indicate their
      potential efficacy as cancer drugs. However, the clinical activity of NAMPT
      inhibitors has proven limited, suggesting that alternative NAD+ production routes
      exploited by tumors confer resistance. Here, we show the gene encoding nicotinic
      acid phosphoribosyltransferase (NAPRT), a second NAD+-producing enzyme, is
      amplified and overexpressed in a subset of common types of cancer, including
      ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression
      signature. Both NAPRT and NAMPT increased intracellular NAD+ levels. NAPRT
      silencing reduced energy status, protein synthesis, and cell size in ovarian and
      pancreatic cancer cells. NAPRT silencing sensitized cells to NAMPT inhibitors
      both in vitro and in vivo; similar results were obtained with the NAPRT inhibitor
      2-hydroxynicotinic acid. Reducing NAPRT levels in a BRCA2-deficient cancer cell
      line exacerbated DNA damage in response to chemotherapeutics. In conclusion,
      NAPRT-dependent NAD+ biosynthesis contributes to cell metabolism and to the DNA
      repair process in a subset of tumors. This knowledge could be used to increase
      the efficacy of NAMPT inhibitors and chemotherapy. Cancer Res; 77(14); 3857-69.
      (c)2017 AACR.

PMID- 28507102
TI  - The FOXO3/PGC-1beta signaling axis is essential for cancer stem cell properties
      of pancreatic ductal adenocarcinoma.
AB  - In 95% of patients with pancreatic ductal adenocarcinoma, recurrence is observed
      following chemotherapy. Findings from several studies have indicated that cancer
      stem cells (CSCs) are resistant to anticancer agents and may be involved in
      cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and
      CD44 also plays an indispensable role in the CSC properties in several cancers,
      including pancreatic cancer; however, no clinical approach exists to inhibit CD44
      activity. Here, we have performed knock-in/knockdown experiments, and we
      demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated
      protein kinase/peroxisome proliferator-activated receptor-gamma co-activator
      1beta (PGC-1beta)/pyruvate dehydrogenase-A1 pathway is essential for CD44
      expression and CSC properties. We observed that patients exhibiting high pyruvate
      dehydrogenase-A1 expression have a poor prognosis. Systemic PGC-1beta knock-out
      mice are fertile and viable and do not exhibit an overt phenotype under normal
      conditions. This suggests that cGMP induction and PGC-1beta inhibition represent
      potential strategies for treating patients with pancreatic ductal adenocarcinoma.

PMID- 28507105
TI  - Reduced Vancomycin Susceptibility of Methicillin-Susceptible Staphylococcus
      aureus Has No Significant Impact on Mortality but Results in an Increase in
      Complicated Infection.
AB  - Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections
      (BSIs) often lead to severe complications despite the availability of effective
      antibiotics. It remains unclear whether elevated vancomycin MICs are associated
      with worse outcomes. We conducted a 2-year retrospective cohort study (n = 252)
      of patients with MSSA BSIs at a tertiary care hospital. We defined reduced
      vancomycin susceptibility (RVS) as a Microscan MIC of 2 mg/liter. All strains
      were genotyped (spa) and assessed for agr functionality. Multivariable logistic
      regression models were used to examine the impact of RVS phenotype and strain
      genotype on 30-day all-cause mortality and complicated bacteremia (metastatic
      spread, endovascular infection, or duration >=3 days). One-third of patients
      (84/252) were infected with RVS isolates. RVS Infections were more frequently
      associated with metastatic or embolic sites of infection (36% versus 17%, P <
      0.001), and endovascular infection (26% versus 12%, P = 0.004). These infections
      occurred more often in patients with fewer underlying comorbidities (Charlson
      comorbidity index of >=3 [73% versus 88%, P = 0.002]). Genotyping identified 127
      spa-types and 14 Spa-clonal complexes (Spa-CCs). Spa-CC002 and Spa-CC008 were
      more likely to exhibit the RVS phenotype versus other Spa-CCs (OR = 2.2, P <
      0.01). The RVS phenotype was not significantly associated with 30-day mortality;
      however, it was associated with complicated bacteremia (adjusted odds ratio of
      2.35 [range, 1.26 to 4.37]; P = 0.007) in adjusted analyses. The association of
      RVS strains with complicated infection and fewer underlying comorbidities
      suggests the phenotype as a potential marker of strain virulence in MSSA BSIs.
      The RVS phenotype itself was not a significant predictor of mortality in this
      patient cohort. Further studies are necessary to explore this host-pathogen
      relationship.

PMID- 28507106
TI  - Efficacy and Pharmacokinetics of the Combination of OP0595 and Cefepime in a
      Mouse Model of Pneumonia Caused by Extended-Spectrum-Beta-Lactamase-Producing
      Klebsiella pneumoniae.
AB  - OP0595 (RG6080) is a novel diazabicyclooctane that inhibits class A and C serine
      beta-lactamases. Although the combination of OP0595 and cefepime (FEP) showed
      good in vitro activity against extended-spectrum-beta-lactamase (ESBL)-producing
      pathogens, the effect of the combination therapy against severe infections, such
      as pneumonia or bacteremia, remains unknown in vivo In this study, we
      investigated the efficacy and pharmacokinetics of the combination therapy of
      OP0595 and FEP in a mouse model of pneumonia caused by Klebsiella pneumoniae
      harboring SHV- and CTX-M-9-type ESBLs. The infected BALB/c mice were
      intraperitoneally administered saline (control), 100 mg/kg of body weight of FEP,
      20 mg/kg of OP0595, or both FEP and OP0595, twice a day. The MIC of FEP against
      the bacteria was 8 mg/liter and markedly improved to 0.06 mg/liter with the
      addition of 0.5 mg/ml of OP0595. In the survival study, the combination of FEP
      and OP0595 significantly improved the survival rate compared with that reported
      with either OP0595 or FEP alone (P < 0.001). The number of bacteria in the lungs
      and blood significantly decreased in the combination therapy group compared to
      that reported for the monotherapy groups (P < 0.001). In addition, the in vivo
      effect depended on the dose of FEP. However, pharmacokinetic analysis revealed
      that the percentage of time above MIC remained constant when increasing the dose
      of FEP in combination with 20 mg/kg of OP0595. The results of our study
      demonstrated the in vivo effectiveness of the combination of OP0595 and FEP.

PMID- 28507107
TI  - In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150,
      Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical
      Development for the Prevention of HIV-1 Infection.
AB  - Rilpivirine (RPV), dapivirine (DPV), and MIV-150 are in development as
      microbicides. It is not known whether they will block infection of circulating
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant human
      immunodeficiency virus type 1 (HIV-1) variants. Here, we demonstrate that the
      activity of DPV and MIV-150 is compromised by many resistant viruses containing
      single or double substitutions. High DPV genital tract concentrations from DPV
      ring use may block replication of resistant viruses. However, MIV-150 genital
      tract concentrations may be insufficient to inhibit many resistant viruses,
      including those harboring K103N or Y181C.

PMID- 28507108
TI  - Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral,
      ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized,
      Controlled Study.
AB  - We investigated the safety and antiviral effects of an anti-HIV compound (ABX464)
      with a unique mechanism of viral replication inhibition. This was a randomized,
      double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV
      infected patients. Participants were assigned to eight groups; each group
      included eight subjects receiving either the study compound, ABX464 (n = 6), or
      the corresponding placebo (n = 2), according to a randomization code. The first
      dose administered was 25 mg, given once or 3 times a day over a 2- to 3-week
      period. Ascending doses of up to 150 mg were delivered after review of the safety
      data. The primary objective of the study was to assess the safety and
      tolerability of ABX464 after repeated oral administrations in subjects infected
      by HIV. Sixty-six subjects were enrolled and were randomized. Sixty-three
      subjects completed the study according to the study protocol. Twenty-one adverse
      events (AEs) were reported by 7 subjects out of 16 (44%) who received placebo,
      and 158 AEs were reported by 39 subjects out of 50 (78%) who received the study
      drug. In the ABX464 treatment group, all of these adverse events were mild to
      moderate. No subjects discontinued treatment due to drug-related AEs.
      Administration of ABX464 at up to 150 mg once a day was safe and well tolerated
      in HIV-infected subjects. An efficacy signal with respect to a reduction of the
      viral load by ABX464 was detected, mainly in subjects treated at the highest
      dose. Further studies will be required to demonstrate antiviral effects in HIV
      infected subjects in combination with other antiretroviral therapies. (This study
      is registered on the ClinicalTrials.gov website under registration no.
      NCT02452242.).

PMID- 28507110
TI  - Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material
      for Inhibition of Staphylococcus aureus Biofilm.
AB  - Staphylococcus aureus is a major human pathogen in catheter-related infections.
      Modifying catheter material with interpenetrating polymer networks is a novel
      material technology that allows for impregnation with drugs and subsequent
      controlled release. Here, we evaluated the potential for combining this system
      with plectasin derivate NZ2114 in an attempt to design an S. aureus biofilm
      resistant catheter. The material demonstrated promising antibiofilm properties,
      including properties against methicillin-resistant S. aureus, thus suggesting a
      novel application of this antimicrobial peptide.

PMID- 28507109
TI  - ERG11 Gene Mutations and MDR1 Upregulation Confer Pan-Azole Resistance in Candida
      tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia
      Patient on Posaconazole Prophylaxis.
AB  - In this study, we present a rare case of fatal breakthrough Candida tropicalis
      infection in a patient with acute lymphoblastic leukemia (ALL) while on
      posaconazole prophylaxis. Then, we explore the mechanisms underlying azole
      resistance by focusing on enhanced efflux pumps and changes in the azole target
      enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that
      Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan
      azole resistance mechanisms in Candida tropicalis.

PMID- 28507111
TI  - Real-Life Assessment of the Safety and Effectiveness of the New Tablet and
      Intravenous Formulations of Posaconazole in the Prophylaxis of Invasive Fungal
      Infections via Analysis of 343 Courses.
AB  - Posaconazole is the preferred mold-active azole for prophylaxis against invasive
      fungal infections (IFIs) in patients with hematological malignancy. Delayed
      release tablet and intravenous formulations of posaconazole have recently become
      available, but clinical data are limited. We sought to examine the real-world
      pharmacokinetics and prophylactic effectiveness of the new formulations of
      posaconazole given as prophylaxis for patients with hematological malignancy. A
      retrospective cohort of all consecutive adult inpatients with hematological
      malignancy who received >=3 days of tablet or intravenous posaconazole therapy
      for primary IFI prophylaxis at the M. D. Anderson Cancer Center between 1
      December 2013 and 31 December 2015 was established. Clinical information was
      collected and correlated with low posaconazole serum levels (<700 ng/ml). Rates
      of IFIs and safety events were assessed. A total of 1,321 courses of posaconazole
      were administered at the M. D. Anderson Cancer Center during the study period, of
      which 343 courses were assessed for prophylactic safety and effectiveness.
      Seventy-nine patients (23%) had posaconazole serum level measurements available
      for interpretation. Acute myeloid leukemia was the primary malignancy (62%), with
      20% of all patients having previously received a stem cell transplant. The median
      posaconazole level was 1,380 ng/ml (interquartile range, 864 to 1,860 ng/ml). Low
      posaconazole levels (<700 ng/ml) were observed for 14 patients (18%). Proven or
      probable breakthrough IFIs occurred in 8 patients (2%); posaconazole therapeutic
      drug monitoring (TDM) was performed for 6 of those patients, all with levels
      above 700 ng/ml. Overall, 19% of patients experienced grade 3 or 4 liver injury,
      manifesting primarily as hyperbilirubinemia and being correlated with serum
      levels of >1,830 ng/ml. Although hepatotoxicity in a small percentage of patients
      is of concern, posaconazole tablets appeared to be generally safe and effective.
      As all breakthrough IFIs for which TDM was performed occurred in patients with
      levels of >700 ng/ml, and a posaconazole level of >1,830 ng/ml was correlated
      with grade 3 or 4 liver toxicity, further studies are needed to assess the role
      of TDM.

PMID- 28507112
TI  - MCR-1 and OXA-48 In Vivo Acquisition in KPC-Producing Escherichia coli after
      Colistin Treatment.
AB  - The spread of mcr-1-encoding plasmids into carbapenem-resistant
      Enterobacteriaceae raises concerns about the emergence of untreatable bacteria.
      We report the acquisition of mcr-1 in a carbapenem-resistant Escherichia coli
      strain after a 3-week course of colistin in a patient repatriated to France from
      Portugal. Whole-genome sequencing revealed that the Klebsiella pneumoniae
      carbapenemase-producing E. coli strain acquired two plasmids, an IncL OXA-48
      encoding plasmid and an IncX4 mcr-1-encoding plasmid. This is the first report of
      mcr-1 in carbapenemase-encoding bacteria in France.

PMID- 28507114
TI  - Antiviral Activity of Nordihydroguaiaretic Acid and Its Derivative Tetra-O-Methyl
      Nordihydroguaiaretic Acid against West Nile Virus and Zika Virus.
AB  - Flaviviruses are positive-strand RNA viruses distributed all over the world that
      infect millions of people every year and for which no specific antiviral agents
      have been approved. These viruses include the mosquito-borne West Nile virus
      (WNV), which is responsible for outbreaks of meningitis and encephalitis.
      Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to
      inhibit the multiplication of the related dengue virus and hepatitis C virus, we
      have evaluated the effect of NDGA, and its methylated derivative tetra-O-methyl
      nordihydroguaiaretic acid (M4N), on the infection of WNV. Both compounds
      inhibited the infection of WNV, likely by impairing viral replication. Since
      flavivirus multiplication is highly dependent on host cell lipid metabolism, the
      antiviral effect of NDGA has been previously related to its ability to disturb
      the lipid metabolism, probably by interfering with the sterol regulatory element
      binding proteins (SREBP) pathway. Remarkably, we observed that other structurally
      unrelated inhibitors of the SREBP pathway, such as PF-429242 and fatostatin, also
      reduced WNV multiplication, supporting that the SREBP pathway may constitute a
      druggable target suitable for antiviral intervention against flavivirus
      infection. Moreover, treatment with NDGA, M4N, PF-429242, and fatostatin also
      inhibited the multiplication of the mosquito-borne flavivirus Zika virus (ZIKV),
      which has been recently associated with birth defects (microcephaly) and
      neurological disorders. Our results point to SREBP inhibitors, such as NDGA and
      M4N, as potential candidates for further antiviral development against medically
      relevant flaviviruses.

PMID- 28507115
TI  - Sensitivity of White and Opaque Candida albicans Cells to Antifungal Drugs.
AB  - White and opaque cells of Candida albicans have the same genome but differ in
      gene expression patterns, metabolic profiles, and host niche preferences. We
      tested whether these differences, which include the differential expression of
      drug transporters, resulted in different sensitivities to 27 antifungal agents.
      The analysis was performed in two different strain backgrounds; although there
      was strain-to-strain variation, only terbinafine hydrochloride and caspofungin
      showed consistent, 2-fold differences between white and opaque cells across both
      strains.

PMID- 28507113
TI  - Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous
      Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and
      Its Inhibitory Effect on Topoisomerase 1B.
AB  - Leishmaniasis is a disease found throughout the (sub)tropical parts of the world
      caused by protozoan parasites of the Leishmania genus. Despite the numerous
      problems associated with existing treatments, pharmaceutical companies continue
      to neglect the development of better ones. The high toxicity of current drugs
      combined with emerging resistance makes the discovery of new therapeutic
      alternatives urgent. We report here the evaluation of a binuclear cyclopalladated
      complex containing Pd(II) and N,N'-dimethylbenzylamine (Hdmba) against Leishmania
      amazonensis The compound [Pd(dmba)(MU-N3)]2 (CP2) inhibits promastigote growth
      (50% inhibitory concentration [IC50] = 13.2 +/- 0.7 MUM) and decreases the
      proliferation of intracellular amastigotes in in vitro incubated macrophages
      (IC50 = 10.2 +/- 2.2 MUM) without a cytotoxic effect when tested against
      peritoneal macrophages (50% cytotoxic concentration = 506.0 +/- 10.7 MUM). In
      addition, CP2 was also active against T. cruzi intracellular amastigotes (IC50 =
      2.3 +/- 0.5 MUM, selective index = 225), an indication of its potential for use
      in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c
      showed an 80% reduction in parasite load compared to infected and nontreated
      animals. Also, compared to amphotericin B treatment, CP2 did not show any side
      effects, which was corroborated by the analysis of plasma levels of different
      hepatic and renal biomarkers. Furthermore, CP2 was able to inhibit Leishmania
      donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this
      parasite. (This study has been registered at ClinicalTrials.gov under identifier
      NCT02169141.).

PMID- 28507116
TI  - Toxic Electrophiles Induce Expression of the Multidrug Efflux Pump MexEF-OprN in
      Pseudomonas aeruginosa through a Novel Transcriptional Regulator, CmrA.
AB  - The multidrug efflux system MexEF-OprN is produced at low levels in wild-type
      strains of Pseudomonas aeruginosa However, in so-called nfxC mutants, mutational
      alteration of the gene mexS results in constitutive overexpression of the pump,
      along with increased resistance of the bacterium to chloramphenicol,
      fluoroquinolones, and trimethoprim. In this study, analysis of in vitro-selected
      chloramphenicol-resistant clones of strain PA14 led to the identification of a
      new class of MexEF-OprN-overproducing mutants (called nfxC2) exhibiting
      alterations in an as-yet-uncharacterized gene, PA14_38040 (homolog of PA2047 in
      strain PAO1). This gene is predicted to encode an AraC-like transcriptional
      regulator and was called cmrA (for chloramphenicol resistance activator). In
      nfxC2 mutants, the mutated CmrA increases its proper gene expression and
      upregulates the operon mexEF-oprN through MexS and MexT, resulting in a multidrug
      resistance phenotype without significant loss in bacterial virulence.
      Transcriptomic experiments demonstrated that CmrA positively regulates a small
      set of 11 genes, including PA14_38020 (homolog of PA2048), which is required for
      the MexS/T-dependent activation of mexEF-oprN PA2048 codes for a protein sharing
      conserved domains with the quinol monooxygenase YgiN from Escherichia coli
      Interestingly, exposure of strain PA14 to toxic electrophilic molecules (glyoxal,
      methylglyoxal, and cinnamaldehyde) strongly activates the CmrA pathway and
      upregulates MexEF-OprN and, thus, increases the resistance of P. aeruginosa to
      the pump substrates. A picture emerges in which MexEF-OprN is central in the
      response of the pathogen to stresses affecting intracellular redox homeostasis.

PMID- 28507117
TI  - Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant
      Tuberculosis Patients.
AB  - Pharmacodynamics are especially important in the treatment of multidrug- and
      extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the
      concentration time curve in relation to MIC (fAUC/MIC) is the most relevant
      pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy
      of levofloxacin (LFX). The objective of our study was to assess LFX PK
      variability in M/XDR-TB patients and its potential consequence for fAUC/MIC
      ratios. Patients with pulmonary M/XDR-TB received LFX as part of the treatment
      regimen at a dose of 15 mg/kg administered once daily. Blood samples obtained at
      steady state before and 1, 2, 3, 4, 7, and 12 h after drug administration were
      measured by validated liquid chromatography-tandem mass spectrometry. The MIC
      values of LFX were determined by the agar dilution method on Middlebrook 7H10 and
      the MGIT960 system. Twenty patients with a mean age of 31 years (interquartile
      range [IQR] = 27 to 35 years) were enrolled in this study. The median AUC0-24 was
      98.8 mg/h/liter (IQR = 84.8 to 159.6 mg/h/liter). The MIC median value for LFX
      was 0.5 mg/liter with a range of 0.25 to 2.0 mg/liter, and the median fAUC0
      24/MIC ratio was 109.5 (IQR = 48.5 to 399.4). In 4 of the 20 patients, the value
      was below the target value of >=100. When MICs of 0.25, 0.5, 1.0, and 2.0
      mg/liter were applicable, 19, 18, 3, and no patients, respectively, had an
      fAUC/MIC ratio that exceeded 100. We observed a large variability in AUC. An
      fAUC0-24/MIC of >=100 was only observed when the MIC values for LFX were 0.25 to
      0.5 mg/liter. Dosages exceeding 15 mg/kg should be considered for target
      attainment if exposures are assumed to be safe. (This study has been registered
      at ClinicalTrials.gov under registration no. NCT02169141.).

PMID- 28507118
TI  - Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by
      Chromosomal Integration of Plasmid DNA.
AB  - Here we describe the spread of colistin resistance in clinical isolates of
      carbapenem-resistant Klebsiella pneumoniae in Medellin, Colombia. Among 32
      isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB
      Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus
      variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25,
      indicating a clonal expansion of the resistant strain. The insertion region
      showed 100% identity to several plasmids, suggesting that the colistin resistance
      is mediated by chromosomal integration of plasmid DNA.

PMID- 28507120
TI  - Highly active catalyst derived from a 3D foam of Fe(PO3)2/Ni2P for extremely
      efficient water oxidation.
AB  - Commercial hydrogen production by electrocatalytic water splitting will benefit
      from the realization of more efficient and less expensive catalysts compared with
      noble metal catalysts, especially for the oxygen evolution reaction, which
      requires a current density of 500 mA/cm2 at an overpotential below 300 mV with
      long-term stability. Here we report a robust oxygen-evolving electrocatalyst
      consisting of ferrous metaphosphate on self-supported conductive nickel foam that
      is commercially available in large scale. We find that this catalyst, which may
      be associated with the in situ generated nickel-iron oxide/hydroxide and iron
      oxyhydroxide catalysts at the surface, yields current densities of 10 mA/cm2 at
      an overpotential of 177 mV, 500 mA/cm2 at only 265 mV, and 1,705 mA/cm2 at 300
      mV, with high durability in alkaline electrolyte of 1 M KOH even after 10,000
      cycles, representing activity enhancement by a factor of 49 in boosting water
      oxidation at 300 mV relative to the state-of-the-art IrO2 catalyst.

PMID- 28507119
TI  - Regulation of the sperm calcium channel CatSper by endogenous steroids and plant
      triterpenoids.
AB  - The calcium channel of sperm (CatSper) is essential for sperm hyperactivated
      motility and fertility. The steroid hormone progesterone activates CatSper of
      human sperm via binding to the serine hydrolase ABHD2. However, steroid
      specificity of ABHD2 has not been evaluated. Here, we explored whether steroid
      hormones to which human spermatozoa are exposed in the male and female genital
      tract influence CatSper activation via modulation of ABHD2. The results show that
      testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents,
      whereas the neurosteroid pregnenolone sulfate exerted similar effects as
      progesterone, likely binding to the same site. However, physiological
      concentrations of testosterone and hydrocortisone inhibited CatSper activation by
      progesterone. Additionally, testosterone antagonized the effect of pregnenolone
      sulfate. We have also explored whether steroid-like molecules, such as the plant
      triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both
      compounds competed with progesterone and pregnenolone sulfate and significantly
      reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol
      considerably diminished hyperactivation of capacitated spermatozoa. These results
      indicate that (i) pregnenolone sulfate together with progesterone are the main
      steroids that activate CatSper and (ii) pristimerin and lupeol can act as
      contraceptive compounds by averting sperm hyperactivation, thus preventing
      fertilization.

PMID- 28507121
TI  - Essential information: Uncertainty and optimal control of Ebola outbreaks.
AB  - Early resolution of uncertainty during an epidemic outbreak can lead to rapid and
      efficient decision making, provided that the uncertainty affects prioritization
      of actions. The wide range in caseload projections for the 2014 Ebola outbreak
      caused great concern and debate about the utility of models. By coding and
      running 37 published Ebola models with five candidate interventions, we found
      that, despite this large variation in caseload projection, the ranking of
      management options was relatively consistent. Reducing funeral transmission and
      reducing community transmission were generally ranked as the two best options.
      Value of information (VoI) analyses show that caseloads could be reduced by 11%
      by resolving all model-specific uncertainties, with information about model
      structure accounting for 82% of this reduction and uncertainty about caseload
      only accounting for 12%. Our study shows that the uncertainty that is of most
      interest epidemiologically may not be the same as the uncertainty that is most
      relevant for management. If the goal is to improve management outcomes, then the
      focus of study should be to identify and resolve those uncertainties that most
      hinder the choice of an optimal intervention. Our study further shows that
      simplifying multiple alternative models into a smaller number of relevant groups
      (here, with shared structure) could streamline the decision-making process and
      may allow for a better integration of epidemiological modeling and decision
      making for policy.

PMID- 28507123
TI  - Large-moment antiferromagnetic order in overdoped high-Tc superconductor
      154SmFeAsO1-x D x.
AB  - In iron-based superconductors, high critical temperature (Tc) superconductivity
      over 50 K has only been accomplished in electron-doped hREFeAsO (hRE is heavy
      rare earth (RE) element). Although hREFeAsO has the highest bulk Tc (58 K),
      progress in understanding its physical properties has been relatively slow due to
      difficulties in achieving high-concentration electron doping and carrying out
      neutron experiments. Here, we present a systematic neutron powder diffraction
      study of 154SmFeAsO1-x D x , and the discovery of a long-range antiferromagnetic
      ordering with x >= 0.56 (AFM2) accompanying a structural transition from
      tetragonal to orthorhombic. Surprisingly, the Fe magnetic moment in AFM2 reaches
      a magnitude of 2.73 MUB/Fe, which is the largest in all nondoped iron pnictides
      and chalcogenides. Theoretical calculations suggest that the AFM2 phase
      originates in kinetic frustration of the Fe-3dxy orbital, in which the nearest
      neighbor hopping parameter becomes zero. The unique phase diagram, i.e., highest
      Tc superconducting phase adjacent to the strongly correlated phase in electron
      overdoped regime, yields important clues to the unconventional origins of
      superconductivity.

PMID- 28507125
TI  - Effective control of complex turbulent dynamical systems through statistical
      functionals.
AB  - Turbulent dynamical systems characterized by both a high-dimensional phase space
      and a large number of instabilities are ubiquitous among complex systems in
      science and engineering, including climate, material, and neural science. Control
      of these complex systems is a grand challenge, for example, in mitigating the
      effects of climate change or safe design of technology with fully developed shear
      turbulence. Control of flows in the transition to turbulence, where there is a
      small dimension of instabilities about a basic mean state, is an important and
      successful discipline. In complex turbulent dynamical systems, it is impossible
      to track and control the large dimension of instabilities, which strongly
      interact and exchange energy, and new control strategies are needed. The goal of
      this paper is to propose an effective statistical control strategy for complex
      turbulent dynamical systems based on a recent statistical energy principle and
      statistical linear response theory. We illustrate the potential practical
      efficiency and verify this effective statistical control strategy on the 40D
      Lorenz 1996 model in forcing regimes with various types of fully turbulent
      dynamics with nearly one-half of the phase space unstable.

PMID- 28507124
TI  - Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes
      with DNA gyrase.
AB  - A paucity of novel acting antibacterials is in development to treat the rising
      threat of antimicrobial resistance, particularly in Gram-negative hospital
      pathogens, which has led to renewed efforts in antibiotic drug discovery.
      Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by
      stabilizing DNA-cleavage complexes, but their clinical utility has been
      compromised by resistance. We have identified a class of antibacterial thiophenes
      that target DNA gyrase with a unique mechanism of action and have activity
      against a range of bacterial pathogens, including strains resistant to
      fluoroquinolones. Although fluoroquinolones stabilize double-stranded DNA breaks,
      the antibacterial thiophenes stabilize gyrase-mediated DNA-cleavage complexes in
      either one DNA strand or both DNA strands. X-ray crystallography of DNA gyrase
      DNA complexes shows the compounds binding to a protein pocket between the winged
      helix domain and topoisomerase-primase domain, remote from the DNA. Mutations of
      conserved residues around this pocket affect activity of the thiophene
      inhibitors, consistent with allosteric inhibition of DNA gyrase. This druggable
      pocket provides potentially complementary opportunities for targeting bacterial
      topoisomerases for antibiotic development.

PMID- 28507122
TI  - Control of metastatic niche formation by targeting APBA3/Mint3 in inflammatory
      monocytes.
AB  - Cancer metastasis is intricately orchestrated by both cancer and normal cells,
      such as endothelial cells and macrophages. Monocytes/macrophages, which are often
      co-opted by cancer cells and promote tumor malignancy, acquire more than half of
      their energy from glycolysis even during normoxic conditions. This glycolytic
      activity is maintained during normoxia by the functions of hypoxia inducible
      factor 1 (HIF-1) and its activator APBA3. The mechanism by which APBA3 inhibition
      partially suppresses macrophage function and affects cancer metastasis is of
      interest in view of avoidance of the adverse effects of complete suppression of
      macrophage function during therapy. Here, we report that APBA3-deficient mice
      show reduced metastasis, with no apparent effect on primary tumor growth. APBA3
      deficiency in inflammatory monocytes, which strongly express the chemokine
      receptor CCR2 and are recruited toward chemokine CCL2 from metastatic sites,
      hampers glycolysis-dependent chemotaxis of cells toward metastatic sites and
      inhibits VEGFA expression, similar to the effects observed with HIF-1 deficiency.
      Host APBA3 induces VEGFA-mediated E-selectin expression in the endothelial cells
      of target organs, thereby promoting extravasation of cancer cells and
      micrometastasis formation. Administration of E-selectin-neutralizing antibody
      also abolished host APBA3-mediated metastatic formation. Thus, targeting APBA3 is
      useful for controlling metastatic niche formation by inflammatory monocytes.

PMID- 28507126
TI  - Direct observation of structure and dynamics during phase separation of an
      elastomeric protein.
AB  - Despite its growing importance in biology and in biomaterials development, liquid
      liquid phase separation of proteins remains poorly understood. In particular, the
      molecular mechanisms underlying simple coacervation of proteins, such as the
      extracellular matrix protein elastin, have not been reported. Coacervation of the
      elastin monomer, tropoelastin, in response to heat and salt is a critical step in
      the assembly of elastic fibers in vivo, preceding chemical cross-linking. Elastin
      like polypeptides (ELPs) derived from the tropoelastin sequence have been shown
      to undergo a similar phase separation, allowing formation of biomaterials that
      closely mimic the material properties of native elastin. We have used NMR
      spectroscopy to obtain site-specific structure and dynamics of a self-assembling
      elastin-like polypeptide along its entire self-assembly pathway, from monomer
      through coacervation and into a cross-linked elastic material. Our data reveal
      that elastin-like hydrophobic domains are composed of transient beta-turns in a
      highly dynamic and disordered chain, and that this disorder is retained both
      after phase separation and in elastic materials. Cross-linking domains are also
      highly disordered in monomeric and coacervated ELP3 and form stable helices only
      after chemical cross-linking. Detailed structural analysis combined with dynamic
      measurements from NMR relaxation and diffusion data provides direct evidence for
      an entropy-driven mechanism of simple coacervation of a protein in which
      transient and nonspecific intermolecular hydrophobic contacts are formed by
      disordered chains, whereas bulk water and salt are excluded.

PMID- 28507128
TI  - Exceptional and rapid accumulation of anthropogenic debris on one of the world's
      most remote and pristine islands.
AB  - In just over half a century plastic products have revolutionized human society
      and have infiltrated terrestrial and marine environments in every corner of the
      globe. The hazard plastic debris poses to biodiversity is well established, but
      mitigation and planning are often hampered by a lack of quantitative data on
      accumulation patterns. Here we document the amount of debris and rate of
      accumulation on Henderson Island, a remote, uninhabited island in the South
      Pacific. The density of debris was the highest reported anywhere in the world, up
      to 671.6 items/m2 (mean +/- SD: 239.4 +/- 347.3 items/m2) on the surface of the
      beaches. Approximately 68% of debris (up to 4,496.9 pieces/m2) on the beach was
      buried <10 cm in the sediment. An estimated 37.7 million debris items weighing a
      total of 17.6 tons are currently present on Henderson, with up to 26.8 new
      items/m accumulating daily. Rarely visited by humans, Henderson Island and other
      remote islands may be sinks for some of the world's increasing volume of waste.

PMID- 28507127
TI  - Development of visual category selectivity in ventral visual cortex does not
      require visual experience.
AB  - To what extent does functional brain organization rely on sensory input? Here, we
      show that for the penultimate visual-processing region, ventral-temporal cortex
      (VTC), visual experience is not the origin of its fundamental organizational
      property, category selectivity. In the fMRI study reported here, we presented 14
      congenitally blind participants with face-, body-, scene-, and object-related
      natural sounds and presented 20 healthy controls with both auditory and visual
      stimuli from these categories. Using macroanatomical alignment, response mapping,
      and surface-based multivoxel pattern analysis, we demonstrated that VTC in blind
      individuals shows robust discriminatory responses elicited by the four categories
      and that these patterns of activity in blind subjects could successfully predict
      the visual categories in sighted controls. These findings were confirmed in a
      subset of blind participants born without eyes and thus deprived from all light
      perception since conception. The sounds also could be decoded in primary visual
      and primary auditory cortex, but these regions did not sustain generalization
      across modalities. Surprisingly, although not as strong as visual responses,
      selectivity for auditory stimulation in visual cortex was stronger in blind
      individuals than in controls. The opposite was observed in primary auditory
      cortex. Overall, we demonstrated a striking similarity in the cortical response
      layout of VTC in blind individuals and sighted controls, demonstrating that the
      overall category-selective map in extrastriate cortex develops independently from
      visual experience.

PMID- 28507129
TI  - Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy
      symptoms in mouse models.
AB  - Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a
      loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or
      pharmacologic orexin replacement ameliorates symptoms in mouse models of
      narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R
      selective agonist, YNT-185. This study validates the pharmacological activity of
      this compound in OX2R-transfected cells and in OX2R-expressing neurons in brain
      slice preparations. Intraperitoneal, and intracerebroventricular, administration
      of YNT-185 suppressed cataplexy-like episodes in orexin knockout and orexin
      neuron-ablated mice, but not in orexin receptor-deficient mice. Peripherally
      administered YNT-185 also promotes wakefulness without affecting body temperature
      in wild-type mice. Further, there was no immediate rebound sleep after YNT-185
      administration in active phase in wild-type and orexin-deficient mice. No
      desensitization was observed after repeated administration of YNT-185 with
      respect to the suppression of cataplexy-like episodes. These results provide a
      proof-of-concept for a mechanistic therapy of narcolepsy-cataplexy by OX2R
      agonists.

PMID- 28507130
TI  - Spatially restricted dental regeneration drives pufferfish beak development.
AB  - Vertebrate dentitions are extraordinarily diverse in both morphology and
      regenerative capacity. The teleost order Tetraodontiformes exhibits an
      exceptional array of novel dental morphologies, epitomized by constrained beak
      like dentitions in several families, i.e., porcupinefishes, three-toothed
      pufferfishes, ocean sunfishes, and pufferfishes. Modification of tooth
      replacement within these groups leads to the progressive accumulation of tooth
      generations, underlying the structure of their beaks. We focus on the dentition
      of the pufferfish (Tetraodontidae) because of its distinct dental morphology.
      This complex dentition develops as a result of (i) a reduction in the number of
      tooth positions from seven to one per quadrant during the transition from first
      to second tooth generations and (ii) a dramatic shift in tooth morphogenesis
      following the development of the first-generation teeth, leading to the
      elongation of dental units along the jaw. Gene expression and 1,1'-Dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) lineage tracing reveal a
      putative dental epithelial progenitor niche, suggesting a highly conserved
      mechanism for tooth regeneration despite the development of a unique dentition.
      MicroCT analysis reveals restricted labial openings in the beak, through which
      the dental epithelium (lamina) invades the cavity of the highly mineralized beak.
      Reduction in the number of replacement tooth positions coincides with the
      development of only four labial openings in the pufferfish beak, restricting
      connection of the oral epithelium to the dental cavity. Our data suggest the
      spatial restriction of dental regeneration, coupled with the unique extension of
      the replacement dental units throughout the jaw, are primary contributors to the
      evolution and development of this unique beak-like dentition.

PMID- 28507132
TI  - Identification of Cav2-PKCbeta and Cav2-NOS1 complexes as entities for ultrafast
      electrochemical coupling.
AB  - Voltage-activated calcium (Cav) channels couple intracellular signaling pathways
      to membrane potential by providing Ca2+ ions as second messengers at sufficiently
      high concentrations to modulate effector proteins located in the intimate
      vicinity of those channels. Here we show that protein kinase Cbeta (PKCbeta) and
      brain nitric oxide synthase (NOS1), both identified by proteomic analysis as
      constituents of the protein nano-environment of Cav2 channels in the brain,
      directly coassemble with Cav2.2 channels upon heterologous coexpression. Within
      Cav2.2-PKCbeta and Cav2.2-NOS1 complexes voltage-triggered Ca2+ influx through
      the Cav channels reliably initiates enzymatic activity within milliseconds. Using
      BKCa channels as target sensors for nitric oxide and protein phosphorylation
      together with high concentrations of Ca2+ buffers showed that the complex
      mediated Ca2+ signaling occurs in local signaling domains at the plasma membrane.
      Our results establish Cav2-enzyme complexes as molecular entities for fast
      electrochemical coupling that reliably convert brief membrane depolarization into
      precisely timed intracellular signaling events in the mammalian brain.

PMID- 28507131
TI  - Involvement of a gut-retina axis in protection against dietary glycemia-induced
      age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the major cause of blindness in
      developed nations. AMD is characterized by retinal pigmented epithelial (RPE)
      cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate
      important contributions of dietary patterns to the risk for AMD, but the
      mechanisms relating diet to disease remain unclear. Here we investigate the
      effect on AMD of isocaloric diets that differ only in the type of dietary
      carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia
      (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation
      and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas
      consumption of the lower-glycemia (LG) diet did not. Critically, switching from
      the HG to the LG diet late in life arrested or reversed AMDf. LG diets limited
      the accumulation of advanced glycation end products, long-chain polyunsaturated
      lipids, and their peroxidation end-products and increased C3-carnitine in retina,
      plasma, or urine. Untargeted metabolomics revealed microbial cometabolites,
      particularly serotonin, as protective against AMDf. Gut microbiota were
      responsive to diet, and we identified microbiota in the Clostridiales order as
      being associated with AMDf and the HG diet, whereas protection from AMDf was
      associated with the Bacteroidales order and the LG diet. Network analysis
      revealed a nexus of metabolites and microbiota that appear to act within a gut
      retina axis to protect against diet- and age-induced AMDf. The findings indicate
      a functional interaction between dietary carbohydrates, the metabolome, including
      microbial cometabolites, and AMDf. Our studies suggest a simple dietary
      intervention that may be useful in patients to arrest AMD.

PMID- 28507133
TI  - Cholinergic shaping of neural correlations.
AB  - A primary function of the brain is to form representations of the sensory world.
      Its capacity to do so depends on the relationship between signal correlations,
      associated with neuronal receptive fields, and noise correlations, associated
      with neuronal response variability. It was recently shown that the behavioral
      relevance of sensory stimuli can modify the relationship between signal and noise
      correlations, presumably increasing the encoding capacity of the brain. In this
      work, we use data from the visual cortex of the awake mouse watching naturalistic
      stimuli and show that a similar modification is observed under heightened
      cholinergic modulation. Increasing cholinergic levels in the cortex through
      optogenetic stimulation of basal forebrain cholinergic neurons decreases the
      dependency that is commonly observed between signal and noise correlations.
      Simulations of correlated neural networks with realistic firing statistics
      indicate that this change in the correlation structure increases the encoding
      capacity of the network.

PMID- 28507134
TI  - Dopaminergic modulation of basal ganglia output through coupled excitation
      inhibition.
AB  - Learning and maintenance of skilled movements require exploration of motor space
      and selection of appropriate actions. Vocal learning and social context-dependent
      plasticity in songbirds depend on a basal ganglia circuit, which actively
      generates vocal variability. Dopamine in the basal ganglia reduces trial-to-trial
      neural variability when the bird engages in courtship song. Here, we present
      evidence for a unique, tonically active, excitatory interneuron in the songbird
      basal ganglia that makes strong synaptic connections onto output pallidal
      neurons, often linked in time with inhibitory events. Dopamine receptor activity
      modulates the coupling of these excitatory and inhibitory events in vitro, which
      results in a dynamic change in the synchrony of a modeled population of basal
      ganglia output neurons receiving excitatory and inhibitory inputs. The excitatory
      interneuron thus serves as one biophysical mechanism for the introduction or
      modulation of neural variability in this circuit.

PMID- 28507135
TI  - Parallel memory traces are built after an experience containing aversive and
      appetitive components in the crab Neohelice.
AB  - The neurobiology of learning and memory has been mainly studied by focusing on
      pure aversive or appetitive experiences. Here, we challenged this approach
      considering that real-life stimuli come normally associated with competing
      aversive and appetitive consequences and that interaction between conflicting
      information must be intrinsic part of the memory processes. We used Neohelice
      crabs, taking advantage of two well-described appetitive and aversive learning
      paradigms and combining them in a single training session to evaluate how this
      affects memory. We found that crabs build separate appetitive and aversive
      memories that compete during retrieval but not during acquisition. Which memory
      prevails depends on the balance between the strength of the unconditioned stimuli
      and on the motivational state of the animals. The results indicate that after a
      mix experience with appetitive and aversive consequences, parallel memories are
      established in a way that appetitive and aversive information is stored to be
      retrieved in an opportunistic manner.

PMID- 28507136
TI  - OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and
      stereotypic behavior.
AB  - Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with
      inadequate treatment options that leave most patients with substantial residual
      symptoms. Structural, neurochemical, and behavioral findings point to a
      significant role for basal ganglia circuits and for the glutamate system in OCD.
      Genetic linkage and association studies in OCD point to SLC1A1, which encodes the
      neuronal glutamate/aspartate/cysteine transporter excitatory amino acid
      transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1). However, no
      previous studies have investigated EAAT3 in basal ganglia circuits or in relation
      to OCD-related behavior. Here, we report a model of Slc1a1 loss based on an
      excisable STOP cassette that yields successful ablation of EAAT3 expression and
      function. Using amphetamine as a probe, we found that EAAT3 loss prevents
      expected increases in (i) locomotor activity, (ii) stereotypy, and (iii)
      immediate early gene induction in the dorsal striatum following amphetamine
      administration. Further, Slc1a1-STOP mice showed diminished grooming in an SKF
      38393 challenge experiment, a pharmacologic model of OCD-like grooming behavior.
      This reduced grooming is accompanied by reduced dopamine D1 receptor binding in
      the dorsal striatum of Slc1a1-STOP mice. Slc1a1-STOP mice also exhibit reduced
      extracellular dopamine concentrations in the dorsal striatum both at baseline and
      following amphetamine challenge. Viral-mediated restoration of Slc1a1/EAAT3
      expression in the midbrain but not in the striatum results in partial rescue of
      amphetamine-induced locomotion and stereotypy in Slc1a1-STOP mice, consistent
      with an impact of EAAT3 loss on presynaptic dopaminergic function. Collectively,
      these findings indicate that the most consistently associated OCD candidate gene
      impacts basal ganglia-dependent repetitive behaviors.

PMID- 28507137
TI  - Arabidopsis glycosylphosphatidylinositol-anchored protein LLG1 associates with
      and modulates FLS2 to regulate innate immunity.
AB  - Plants detect and respond to pathogen invasion with membrane-localized pattern
      recognition receptors (PRRs), which recognize pathogen-associated molecular
      patterns (PAMPs) and activate downstream immune responses. Here we report that
      Arabidopsis thaliana LORELEI-LIKE GPI-ANCHORED PROTEIN 1 (LLG1), a coreceptor of
      the receptor-like kinase FERONIA, regulates PRR signaling. In a forward genetic
      screen for suppressors of enhanced disease resistance 1 (edr1), we identified the
      point mutation llg1-3, which suppresses edr1 disease resistance but does not
      affect plant growth and development. The llg1 mutants show enhanced
      susceptibility to various virulent pathogens, indicating that LLG1 has an
      important role in plant immunity. LLG1 constitutively associates with the PAMP
      receptor FLAGELLIN SENSING 2 (FLS2) and the elongation factor-Tu receptor, and
      forms a complex with BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1
      in a ligand-dependent manner, indicating that LLG1 functions as a key component
      of PAMP-recognition immune complexes. Moreover, LLG1 contributes to accumulation
      and ligand-induced degradation of FLS2, and is required for downstream innate
      immunity responses, including ligand-induced phosphorylation of BOTRYTIS-INDUCED
      KINASE 1 and production of reactive oxygen species. Taken together, our findings
      reveal that LLG1 associates with PAMP receptors and modulates their function to
      regulate disease responses. As LLG1 functions as a coreceptor of FERONIA and
      plays central roles in plant growth and development, our findings indicate that
      LLG1 participates in separate pathways, and may suggest a potential connection
      between development and innate immunity in plants.

PMID- 28507138
TI  - Stem cell migration and mechanotransduction on linear stiffness gradient
      hydrogels.
AB  - The spatial presentation of mechanical information is a key parameter for cell
      behavior. We have developed a method of polymerization control in which the
      differential diffusion distance of unreacted cross-linker and monomer into a
      prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell
      matrix interface. This simple, low-cost, robust method was used to produce
      polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and
      8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical
      landscape. Importantly, three of these gradients were found to be nondurotactic
      for human adipose-derived stem cells (hASCs), allowing the presentation of a
      continuous range of stiffnesses in a single well without the confounding effect
      of differential cell migration. Using these nondurotactic gradient gels,
      stiffness-dependent hASC morphology, migration, and differentiation were studied.
      Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF
      B were analyzed on these gradients, providing higher-resolution data on stiffness
      dependent expression and localization.

PMID- 28507140
TI  - Linkage disequilibrium matches forensic genetic records to disjoint genomic
      marker sets.
AB  - Combining genotypes across datasets is central in facilitating advances in
      genetics. Data aggregation efforts often face the challenge of record matching
      the identification of dataset entries that represent the same individual. We show
      that records can be matched across genotype datasets that have no shared markers
      based on linkage disequilibrium between loci appearing in different datasets.
      Using two datasets for the same 872 people-one with 642,563 genome-wide SNPs and
      the other with 13 short tandem repeats (STRs) used in forensic applications-we
      find that 90-98% of forensic STR records can be connected to corresponding SNP
      records and vice versa. Accuracy increases to 99-100% when ~30 STRs are used. Our
      method expands the potential of data aggregation, but it also suggests privacy
      risks intrinsic in maintenance of databases containing even small numbers of
      markers-including databases of forensic significance.

PMID- 28507139
TI  - Long-read sequencing uncovers the adaptive topography of a carnivorous plant
      genome.
AB  - Utricularia gibba, the humped bladderwort, is a carnivorous plant that retains a
      tiny nuclear genome despite at least two rounds of whole genome duplication (WGD)
      since common ancestry with grapevine and other species. We used a third
      generation genome assembly with several complete chromosomes to reconstruct the
      two most recent lineage-specific ancestral genomes that led to the modern U.
      gibba genome structure. Patterns of subgenome dominance in the most recent WGD,
      both architectural and transcriptional, are suggestive of allopolyploidization,
      which may have generated genomic novelty and led to instantaneous speciation.
      Syntenic duplicates retained in polyploid blocks are enriched for transcription
      factor functions, whereas gene copies derived from ongoing tandem duplication
      events are enriched in metabolic functions potentially important for a
      carnivorous plant. Among these are tandem arrays of cysteine protease genes with
      trap-specific expression that evolved within a protein family known to be useful
      in the digestion of animal prey. Further enriched functions among tandem
      duplicates (also with trap-enhanced expression) include peptide transport
      (intercellular movement of broken-down prey proteins), ATPase activities (bladder
      trap acidification and transmembrane nutrient transport), hydrolase and chitinase
      activities (breakdown of prey polysaccharides), and cell-wall dynamic components
      possibly associated with active bladder movements. Whereas independently
      polyploid Arabidopsis syntenic gene duplicates are similarly enriched for
      transcriptional regulatory activities, Arabidopsis tandems are distinct from
      those of U. gibba, while still metabolic and likely reflecting unique adaptations
      of that species. Taken together, these findings highlight the special importance
      of tandem duplications in the adaptive landscapes of a carnivorous plant genome.

PMID- 28507141
TI  - Pulses of Ca2+ coordinate actin assembly and exocytosis for stepwise cell
      extension.
AB  - Many eukaryotic cells grow by extending their cell periphery in pulses. The
      molecular mechanisms underlying this process are not yet fully understood. Here
      we present a comprehensive model of stepwise cell extension by using the unique
      tip growth system of filamentous fungi. Live-cell imaging analysis, including
      superresolution microscopy, revealed that the fungus Aspergillus nidulans extends
      the hyphal tip in an oscillatory manner. The amount of F-actin and secretory
      vesicles (SV) accumulating at the hyphal tip oscillated with a positive temporal
      correlation, whereas vesicle amounts were negatively correlated to the growth
      rate. The intracellular Ca2+ level also pulsed with a positive temporal
      correlation to the amount of F-actin and SV at the hyphal tip. Two Ca2+ channels,
      MidA and CchA, were needed for proper tip growth and the oscillations of actin
      polymerization, exocytosis, and the growth rate. The data indicate a model in
      which transient Ca2+ pluses cause depolymerization of F-actin at the cortex and
      promote SV fusion with the plasma membrane, thereby extending the cell tip. Over
      time, Ca2+ diffuses away and F-actin and SV accumulate again at the hyphal tip.
      Our data provide evidence that temporally controlled actin polymerization and
      exocytosis are coordinated by pulsed Ca2+ influx, resulting in stepwise cell
      extension.

PMID- 28507143
TI  - Controllable load sharing for soft adhesive interfaces on three-dimensional
      surfaces.
AB  - For adhering to three-dimensional (3D) surfaces or objects, current adhesion
      systems are limited by a fundamental trade-off between 3D surface conformability
      and high adhesion strength. This limitation arises from the need for a soft,
      mechanically compliant interface, which enables conformability to nonflat and
      irregularly shaped surfaces but significantly reduces the interfacial fracture
      strength. In this work, we overcome this trade-off with an adhesion-based soft
      gripping system that exhibits enhanced fracture strength without sacrificing
      conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric
      microfibrillar adhesive membrane supported by a pressure-controlled deformable
      gripper body, the proposed soft-gripping system controls the bonding strength by
      changing its internal pressure and exploiting the mechanics of interfacial equal
      load sharing. The soft adhesion system can use up to ~26% of the maximum adhesion
      of the fibrillar membrane, which is 14* higher than the adhering membrane without
      load sharing. Our proposed load-sharing method suggests a paradigm for soft
      adhesion-based gripping and transfer-printing systems that achieves area scaling
      similar to that of a natural gecko footpad.

PMID- 28507142
TI  - Quantitative assessment of passive electrical properties of the cardiac T-tubular
      system by FRAP microscopy.
AB  - Well-coordinated activation of all cardiomyocytes must occur on every heartbeat.
      At the cell level, a complex network of sarcolemmal invaginations, called the
      transverse-axial tubular system (TATS), propagates membrane potential changes to
      the cell core, ensuring synchronous and uniform excitation-contraction coupling.
      Although myocardial conduction of excitation has been widely described, the
      electrical properties of the TATS remain mostly unknown. Here, we exploit the
      formal analogy between diffusion and electrical conductivity to link the latter
      with the diffusional properties of TATS. Fluorescence recovery after
      photobleaching (FRAP) microscopy is used to probe the diffusion properties of
      TATS in isolated rat cardiomyocytes: A fluorescent dextran inside TATS lumen is
      photobleached, and signal recovery by diffusion of unbleached dextran from the
      extracellular space is monitored. We designed a mathematical model to correlate
      the time constant of fluorescence recovery with the apparent diffusion
      coefficient of the fluorescent molecules. Then, apparent diffusion is linked to
      electrical conductivity and used to evaluate the efficiency of the passive spread
      of membrane depolarization along TATS. The method is first validated in cells
      where most TATS elements are acutely detached by osmotic shock and then applied
      to probe TATS electrical conductivity in failing heart cells. We find that acute
      and pathological tubular remodeling significantly affect TATS electrical
      conductivity. This may explain the occurrence of defects in action potential
      propagation at the level of single T-tubules, recently observed in diseased
      cardiomyocytes.

PMID- 28507144
TI  - Critical roles of DNA demethylation in the activation of ripening-induced genes
      and inhibition of ripening-repressed genes in tomato fruit.
AB  - DNA methylation is a conserved epigenetic mark important for genome integrity,
      development, and environmental responses in plants and mammals. Active DNA
      demethylation in plants is initiated by a family of 5-mC DNA glycosylases/lyases
      (i.e., DNA demethylases). Recent reports suggested a role of active DNA
      demethylation in fruit ripening in tomato. In this study, we generated loss-of
      function mutant alleles of a tomato gene, SlDML2, which is a close homolog of the
      Arabidopsis DNA demethylase gene ROS1 In the fruits of the tomato mutants,
      increased DNA methylation was found in thousands of genes. These genes included
      not only hundreds of ripening-induced genes but also many ripening-repressed
      genes. Our results show that SlDML2 is critical for tomato fruit ripening and
      suggest that active DNA demethylation is required for both the activation of
      ripening-induced genes and the inhibition of ripening-repressed genes.

PMID- 28507146
TI  - Further evidence for localized, short-term anthropogenic forest alterations
      across pre-Columbian Amazonia.

PMID- 28507145
TI  - In vivo photolabeling of tumor-infiltrating cells reveals highly regulated egress
      of T-cell subsets from tumors.
AB  - Immune therapy is rapidly gaining prominence in the clinic as a major weapon
      against cancer. Whereas much attention has been focused on the infiltration of
      tumors by immune cells, the subsequent fate of these infiltrates remains largely
      unexplored. We therefore established a photoconversion-based model that allowed
      us to label tumor-infiltrating immune cells and follow their migration. Using
      this system, we identified a population of tumor-experienced cells that emigrate
      from primary tumors to draining lymph nodes via afferent lymphatic vessels.
      Although the majority of tumor-infiltrating cells were myeloid, T cells made up
      the largest population of tumor-egressing leukocytes. Strikingly, the subset
      composition of tumor-egressing T cells was greatly skewed compared with those
      that had infiltrated the tumor and those resident in the draining lymph node.
      Some T-cell subsets such as CD8+ T cells emigrated more readily; others including
      CD4-CD8- T cells were preferentially retained, suggesting that specific
      mechanisms guide immune cell egress from tumors. Furthermore, tumor-egressing T
      cells were more activated and displayed enhanced effector function in comparison
      with their lymph node counterparts. Finally, we demonstrated that tumor
      infiltrating T cells migrate to distant secondary tumors and draining lymph
      nodes, highlighting a mechanism whereby tumor-experienced effector T cells may
      mediate antitumor immunity at metastatic sites. Thus, our results provide
      insights into migration and function of tumor-infiltrating immune cells and the
      role of these cells in tumor immunity outside of primary tumor deposits.

PMID- 28507147
TI  - Plate tectonic regulation of global marine animal diversity.
AB  - Valentine and Moores [Valentine JW, Moores EM (1970) Nature 228:657-659]
      hypothesized that plate tectonics regulates global biodiversity by changing the
      geographic arrangement of continental crust, but the data required to fully test
      the hypothesis were not available. Here, we use a global database of marine
      animal fossil occurrences and a paleogeographic reconstruction model to test the
      hypothesis that temporal patterns of continental fragmentation have impacted
      global Phanerozoic biodiversity. We find a positive correlation between global
      marine invertebrate genus richness and an independently derived quantitative
      index describing the fragmentation of continental crust during supercontinental
      coalescence-breakup cycles. The observed positive correlation between global
      biodiversity and continental fragmentation is not readily attributable to
      commonly cited vagaries of the fossil record, including changing quantities of
      marine rock or time-variable sampling effort. Because many different
      environmental and biotic factors may covary with changes in the geographic
      arrangement of continental crust, it is difficult to identify a specific causal
      mechanism. However, cross-correlation indicates that the state of continental
      fragmentation at a given time is positively correlated with the state of global
      biodiversity for tens of millions of years afterward. There is also evidence to
      suggest that continental fragmentation promotes increasing marine richness, but
      that coalescence alone has only a small negative or stabilizing effect. Together,
      these results suggest that continental fragmentation, particularly during the
      Mesozoic breakup of the supercontinent Pangaea, has exerted a first-order control
      on the long-term trajectory of Phanerozoic marine animal diversity.

PMID- 28507148
TI  - Correction for Hobbie et al., Contrasting nitrogen and phosphorus budgets in
      urban watersheds and implications for managing urban water pollution.

PMID- 28507150
TI  - Trust and the poverty trap.

PMID- 28507151
TI  - Assembly and function of bHLH-PAS complexes.

PMID- 28507149
TI  - Identification of XAF1-MT2A mutual antagonism as a molecular switch in cell-fate
      decisions under stressful conditions.
AB  - XIAP-associated factor 1 (XAF1) is a tumor suppressor that is commonly
      inactivated in multiple human neoplasms. However, the molecular mechanism
      underlying its proapoptotic function remains largely undefined. Here, we report
      that XAF1 induction by heavy metals triggers an apoptotic switch of stress
      response by destabilizing metallothionein 2A (MT2A). XAF1 directly interacts with
      MT2A and facilitates its lysosomal degradation, resulting in the elevation of the
      free intercellular zinc level and subsequent activation of p53 and inactivation
      of XIAP. Intriguingly, XAF1 is activated as a unique transcription target of
      metal-regulatory transcription factor-1 (MTF-1) in signaling apoptosis, and its
      protein is destabilized via the lysosomal pathway by MTF-1-induced MT2A under
      cytostatic stress conditions, indicating the presence of mutual antagonism
      between XAF1 and MT2A. The antagonistic interplay between XAF1 and MT2A acts as a
      key molecular switch in MTF-1-mediated cell-fate decisions and also plays an
      important role in cell response to various apoptotic and survival factors. Wild
      type (WT) XAF1 but not MT2A binding-deficient mutant XAF1 increases the free
      intracellular zinc level and accelerates WT folding of p53 and degradation of
      XIAP. Consistently, XAF1 evokes a more drastic apoptotic effect in p53+/+ versus
      isogenic p53-/- cells. Clinically, expression levels of XAF1 and MT2A are
      inversely correlated in primary colon tumors and multiple cancer cell lines. XAF1
      depleted xenograft tumors display an increased growth rate and a decreased
      apoptotic response to cytotoxic heavy metals with strong MT2A expression.
      Collectively, this study uncovers an important role for XAF1-MT2A antagonism as a
      linchpin to govern cell fate under various stressful conditions including heavy
      metal exposure.

PMID- 28507153
TI  - Overexplaining or underexplaining methane's role in climate change.

PMID- 28507154
TI  - Information socialtaxis and efficient collective behavior emerging in groups of
      information-seeking agents.
AB  - Individual behavior, in biology, economics, and computer science, is often
      described in terms of balancing exploration and exploitation. Foraging has been a
      canonical setting for studying reward seeking and information gathering, from
      bacteria to humans, mostly focusing on individual behavior. Inspired by the
      gradient-climbing nature of chemotaxis, the infotaxis algorithm showed that
      locally maximizing the expected information gain leads to efficient and
      ethological individual foraging. In nature, as well as in theoretical settings,
      conspecifics can be a valuable source of information about the environment.
      Whereas the nature and role of interactions between animals have been studied
      extensively, the design principles of information processing in such groups are
      mostly unknown. We present an algorithm for group foraging, which we term
      "socialtaxis," that unifies infotaxis and social interactions, where each
      individual in the group simultaneously maximizes its own sensory information and
      a social information term. Surprisingly, we show that when individuals aim to
      increase their information diversity, efficient collective behavior emerges in
      groups of opportunistic agents, which is comparable to the optimal group
      behavior. Importantly, we show the high efficiency of biologically plausible
      socialtaxis settings, where agents share little or no information and rely on
      simple computations to infer information from the behavior of their conspecifics.
      Moreover, socialtaxis does not require parameter tuning and is highly robust to
      sensory and behavioral noise. We use socialtaxis to predict distinct optimal
      couplings in groups of selfish vs. altruistic agents, reflecting how it can be
      naturally extended to study social dynamics and collective computation in general
      settings.

PMID- 28507155
TI  - Reply to Piperno et al.: It is too soon to argue for localized, short-term human
      impacts in interfluvial Amazonia.

PMID- 28507152
TI  - Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.
AB  - The estrogen receptor (ER) drives the growth of most luminal breast cancers and
      is the primary target of endocrine therapy. Although ER blockade with drugs such
      as tamoxifen is very effective, a major clinical limitation is the development of
      endocrine resistance especially in the setting of metastatic disease. Preclinical
      and clinical observations suggest that even following the development of
      endocrine resistance, ER signaling continues to exert a pivotal role in tumor
      progression in the majority of cases. Through the analysis of the ER cistrome in
      tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER
      complex that stimulates the transcription of a set of genes, including most
      notably the stem cell factor SOX9, that promote proliferation and a metastatic
      phenotype. We show that up-regulation of SOX9 is sufficient to cause relative
      endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with
      tamoxifen resistance was validated in a unique set of clinical samples supporting
      the need for the development of improved ER antagonists.

PMID- 28507156
TI  - RNA primer-primase complexes serve as the signal for polymerase recycling and
      Okazaki fragment initiation in T4 phage DNA replication.
AB  - The opposite strand polarity of duplex DNA necessitates that the leading strand
      is replicated continuously whereas the lagging strand is replicated in discrete
      segments known as Okazaki fragments. The lagging-strand polymerase sometimes
      recycles to begin the synthesis of a new Okazaki fragment before finishing the
      previous fragment, creating a gap between the Okazaki fragments. The mechanism
      and signal that initiate this behavior-that is, the signaling mechanism-have not
      been definitively identified. We examined the role of RNA primer-primase
      complexes left on the lagging ssDNA from primer synthesis in initiating early
      lagging-strand polymerase recycling. We show for the T4 bacteriophage DNA
      replication system that primer-primase complexes have a residence time similar to
      the timescale of Okazaki fragment synthesis and the ability to block a holoenzyme
      synthesizing DNA and stimulate the dissociation of the holoenzyme to trigger
      polymerase recycling. The collision with primer-primase complexes triggering the
      early termination of Okazaki fragment synthesis has distinct advantages over
      those previously proposed because this signal requires no transmission to the
      lagging-strand polymerase through protein or DNA interactions, the mechanism for
      rapid dissociation of the holoenzyme is always collision, and no unique
      characteristics need to be assigned to either identical polymerase in the
      replisome. We have modeled repeated cycles of Okazaki fragment initiation using a
      collision with a completed Okazaki fragment or primer-primase complexes as the
      recycling mechanism. The results reproduce experimental data, providing insights
      into events related to Okazaki fragment initiation and the overall functioning of
      DNA replisomes.

PMID- 28507158
TI  - Impact of International Monetary Fund programs on child health.
AB  - Parental education is located at the center of global efforts to improve child
      health. In a developing-country context, the International Monetary Fund (IMF)
      plays a crucial role in determining how governments allocate scarce resources to
      education and public health interventions. Under reforms mandated by IMF
      structural adjustment programs, it may become harder for parents to reap the
      benefits of their education due to wage contraction, welfare retrenchment, and
      generalized social insecurity. This study assesses how the protective effect of
      education changes under IMF programs, and thus how parents' ability to guard
      their children's health is affected by structural adjustment. We combine cross
      sectional stratified data (countries, 67; children, 1,941,734) from the
      Demographic and Health Surveys and the Multiple Indicator Cluster Surveys. The
      sample represents ~2.8 billion (about 50%) of the world's population in year
      2000. Based on multilevel models, our findings reveal that programs reduce the
      protective effect of parental education on child health, especially in rural
      areas. For instance, in the absence of IMF programs, living in an household with
      educated parents reduces the odds of child malnourishment by 38% [odds ratio
      (OR), 0.62; 95% CI, 0.66-0.58]; in the presence of programs, this drops to 21%
      (OR, 0.79; 95% CI, 0.86-0.74). In other words, the presence of IMF conditionality
      decreases the protective effect of parents' education on child malnourishment by
      no less than 17%. We observe similar adverse effects in sanitation, shelter, and
      health care access (including immunization), but a beneficial effect in
      countering water deprivation.

PMID- 28507159
TI  - Investigation of hindwing folding in ladybird beetles by artificial elytron
      transplantation and microcomputed tomography.
AB  - Ladybird beetles are high-mobility insects and explore broad areas by switching
      between walking and flying. Their excellent wing transformation systems enabling
      this lifestyle are expected to provide large potential for engineering
      applications. However, the mechanism behind the folding of their hindwings
      remains unclear. The reason is that ladybird beetles close the elytra ahead of
      wing folding, preventing the observation of detailed processes occurring under
      the elytra. In the present study, artificial transparent elytra were transplanted
      on living ladybird beetles, thereby enabling us to observe the detailed wing
      folding processes. The result revealed that in addition to the abdominal
      movements mentioned in previous studies, the edge and ventral surface of the
      elytra, as well as characteristic shaped veins, play important roles in wing
      folding. The structures of the wing frames enabling this folding process and
      detailed 3D shape of the hindwing were investigated using microcomputed
      tomography. The results showed that the tape spring-like elastic frame plays an
      important role in the wing transformation mechanism. Compared with other beetles,
      hindwings in ladybird beetles are characterized by two seemingly incompatible
      properties: (i) the wing rigidity with relatively thick veins and (ii) the
      compactness in stored shapes with complex crease patterns. The detailed wing
      folding process revealed in this study is expected to facilitate understanding of
      the naturally optimized system in this excellent deployable structure.

PMID- 28507157
TI  - Translation and folding of single proteins in real time.
AB  - Protein biosynthesis is inherently coupled to cotranslational protein folding.
      Folding of the nascent chain already occurs during synthesis and is mediated by
      spatial constraints imposed by the ribosomal exit tunnel as well as self
      interactions. The polypeptide's vectorial emergence from the ribosomal tunnel
      establishes the possible folding pathways leading to its native tertiary
      structure. How cotranslational protein folding and the rate of synthesis are
      linked to a protein's amino acid sequence is still not well defined. Here, we
      follow synthesis by individual ribosomes using dual-trap optical tweezers and
      observe simultaneous folding of the nascent polypeptide chain in real time. We
      show that observed stalling during translation correlates with slowed peptide
      bond formation at successive proline sequence positions and electrostatic
      interactions between positively charged amino acids and the ribosomal tunnel. We
      also determine possible cotranslational folding sites initiated by hydrophobic
      collapse for an unstructured and two globular proteins while directly measuring
      initial cotranslational folding forces. Our study elucidates the intricate
      relationship among a protein's amino acid sequence, its cotranslational nascent
      chain elongation rate, and folding.

PMID- 28507160
TI  - Emergent magnetism at transition-metal-nanocarbon interfaces.
AB  - Charge transfer at metallo-molecular interfaces may be used to design
      multifunctional hybrids with an emergent magnetization that may offer an eco
      friendly and tunable alternative to conventional magnets and devices. Here, we
      investigate the origin of the magnetism arising at these interfaces by using
      different techniques to probe 3d and 5d metal films such as Sc, Mn, Cu, and Pt in
      contact with fullerenes and rf-sputtered carbon layers. These systems exhibit
      small anisotropy and coercivity together with a high Curie point. Low-energy muon
      spin spectroscopy in Cu and Sc-C60 multilayers show a quick spin depolarization
      and oscillations attributed to nonuniform local magnetic fields close to the
      metallo-carbon interface. The hybridization state of the carbon layers plays a
      crucial role, and we observe an increased magnetization as sp3 orbitals are
      annealed into sp2-pi graphitic states in sputtered carbon/copper multilayers. X
      ray magnetic circular dichroism (XMCD) measurements at the carbon K edge of C60
      layers in contact with Sc films show spin polarization in the lowest unoccupied
      molecular orbital (LUMO) and higher pi*-molecular levels, whereas the dichroism
      in the sigma*-resonances is small or nonexistent. These results support the idea
      of an interaction mediated via charge transfer from the metal and dz-pi
      hybridization. Thin-film carbon-based magnets may allow for the manipulation of
      spin ordering at metallic surfaces using electrooptical signals, with potential
      applications in computing, sensors, and other multifunctional magnetic devices.

PMID- 28507161
TI  - Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and
      TAB3.
AB  - Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin
      (K63-Ub) chains, which are thought to activate the 'master' protein kinase
      TGFbeta-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2)
      and TAB3 subunits. Here, we report that IL-1beta can also activate the TAB1-TAK1
      heterodimer present in TAB2/TAB3 double knockout (DKO) IL-1 receptor-expressing
      cells. The IL-1beta-dependent activation of the TAB1-TAK1 heterodimer in TAB2/3
      DKO cells is required for the expression and E3 ligase activity of tumor necrosis
      factor receptor-associated factor 6 (TRAF6) and is reduced by the small
      interfering RNA (siRNA) knockdown of ubiquitin conjugating 13 (Ubc13), an E2
      conjugating enzyme that directs the formation of K63-Ub chains. IL-1beta
      signaling was restored to TAB1/2/3 triple KO cells by the re-expression of either
      TAB1 or TAB2, but not by an ubiquitin binding-defective mutant of TAB2. We
      conclude that IL-1beta can induce the activation of TAK1 in two ways, only one of
      which requires the binding of K63-Ub chains to TAB2/3. The early IL-1beta
      stimulated, TAK1-dependent activation of p38alpha mitogen-activated protein (MAP)
      kinase and the canonical IkappaB kinase (IKK) complex, as well as the NF-kappaB
      dependent transcription of immediate early genes, was similar in TAB2/3 DKO cells
      and TAB2/3-expressing cells. However, in contrast with TAB2/3-expressing cells,
      IL-1beta signaling was transient in TAB2/3 DKO cells, and the activation of c-Jun
      N-terminal kinase 1 (JNK1), JNK2 and p38gamma was greatly reduced at all times.
      These observations indicate a role for TAB2/3 in directing the TAK1-dependent
      activation of MAP kinase kinases that switch on JNK1/2 and p38gamma MAP kinases.
      These observations and the transient activation of the TAB1-TAK1 heterodimer may
      explain why IL-1beta-dependent IL-8 mRNA formation was abolished in TAB2/3 DKO
      cells.

PMID- 28507162
TI  - Lipophagy prevents activity-dependent neurodegeneration due to dihydroceramide
      accumulation in vivo.
AB  - Dihydroceramide desaturases are evolutionarily conserved enzymes that convert
      dihydroceramide (dhCer) to ceramide (Cer). While elevated Cer levels cause
      neurodegenerative diseases, the neuronal activity of its direct precursor, dhCer,
      remains unclear. We show that knockout of the fly dhCer desaturase gene,
      infertile crescent (ifc), results in larval lethality with increased dhCer and
      decreased Cer levels. Light stimulation leads to ROS increase and apoptotic cell
      death in ifc-KO photoreceptors, resulting in activity-dependent
      neurodegeneration. Lipid-containing Atg8/LC3-positive puncta accumulate in ifc-KO
      photoreceptors, suggesting lipophagy activation. Further enhancing lipophagy
      reduces lipid droplet accumulation and rescues ifc-KO defects, indicating that
      lipophagy plays a protective role. Reducing dhCer synthesis prevents
      photoreceptor degeneration and rescues ifc-KO lethality, while supplementing
      downstream sphingolipids does not. These results pinpoint that dhCer accumulation
      is responsible for ifc-KO defects. Human dhCer desaturase rescues ifc-KO larval
      lethality, and rapamycin reverses defects caused by dhCer accumulation in human
      neuroblastoma cells, suggesting evolutionarily conserved functions. This study
      demonstrates a novel requirement for dhCer desaturase in neuronal maintenance in
      vivo and shows that lipophagy activation prevents activity-dependent degeneration
      caused by dhCer accumulation.

PMID- 28507164
TI  - Reliability of low-power cycling efficiency in energy expenditure phenotyping of
      inactive men and women.
AB  - Standardized approaches to assess human energy expenditure (EE) are well defined
      at rest and at moderate to high-intensity exercise, but not at light intensity
      physical activities energetically comparable with those of daily life (i.e., 1.5
      4 times the resting EE, i.e., 1.5-4 METs). Our aim was to validate a graded
      exercise test for assessing the energy cost of low-intensity dynamic work in
      physically inactive humans, that is, those who habitually do not meet the
      guidelines for moderate-to-vigorous aerobic physical activity levels. In healthy
      and inactive young men and women (n = 55; aged 18-32 years), EE was assessed in
      the overnight-fasted state by indirect calorimetry at rest and during graded
      cycling between 5 and 50W for 5 min at each power output on a bicycle ergometer.
      Repeatability was investigated on three separate days, and the effect of cadence
      was investigated in the range of 40-90 rpm. Within the low power range of
      cycling, all subjects perceived the exercise test as "light" on the Borg scale,
      the preferred cadence being 60 rpm. A strong linearity of the EE-power
      relationship was observed between 10 and 50 W for each individual (r > 0.98), and
      the calculation of delta efficiency (DE) from the regression slope indicated that
      DE was similar in men and women (~29%). DE showed modest inter-individual
      variability with a coefficient of variation (CV) of 11%, and a low intra
      individual variability with a CV of ~ 5%. No habituation or learning effect was
      observed in DE across days. In conclusion, the assessment of the efficiency of
      low power cycling by linear regression - and conducted within the range of EE
      observed for low-intensity movements of everyday life (1.5-4 METs) - extends the
      capacity for metabolic phenotyping in the inactive population.

PMID- 28507163
TI  - Ca2+ binding to F-ATP synthase beta subunit triggers the mitochondrial
      permeability transition.
AB  - F-ATP synthases convert the electrochemical energy of the H+ gradient into the
      chemical energy of ATP with remarkable efficiency. Mitochondrial F-ATP synthases
      can also undergo a Ca2+-dependent transformation to form channels with properties
      matching those of the permeability transition pore (PTP), a key player in cell
      death. The Ca2+ binding site and the mechanism(s) through which Ca2+ can
      transform the energy-conserving enzyme into a dissipative structure promoting
      cell death remain unknown. Through in vitro, in vivo and in silico studies we (i)
      pinpoint the "Ca2+-trigger site" of the PTP to the catalytic site of the F-ATP
      synthase beta subunit and (ii) define a conformational change that propagates
      from the catalytic site through OSCP and the lateral stalk to the inner membrane.
      T163S mutants of the beta subunit, which show a selective decrease in Ca2+-ATP
      hydrolysis, confer resistance to Ca2+-induced, PTP-dependent death in cells and
      developing zebrafish embryos. These findings are a major advance in the molecular
      definition of the transition of F-ATP synthase to a channel and of its role in
      cell death.

PMID- 28507165
TI  - Reliability and validity of an agility-like incremental exercise test with
      multidirectional change-of-direction movements in response to a visual stimulus.
AB  - The aim of the study was to evaluate the reliability and validity of
      cardiorespiratory and metabolic variables, that is, peak oxygen uptake (V'O2peak)
      and heart rate (HRpeak), obtained from an agility-like incremental exercise test
      for team sport athletes. To investigate the test-retest reliability, 25 team
      sport athletes (age: 22 +/- 3 years, body mass: 75 +/- 7 kg, height: 182 +/- 6
      cm) performed an agility-like incremental exercise test on the SpeedCourt (SC)
      system incorporating multidirectional change-of-direction (COD) movements twice.
      For each step of the incremental SC test, the athletes covered a 40-m distance
      interspersed with a 10-sec rest period. Each 40 m distance was split into short
      sprints (2.25-6.36 m) separated by multidirectional COD movements (0 degrees -180
      degrees ), which were performed in response to an external visual stimulus. All
      performance and physiological data were validated with variables obtained from a
      ramp-like treadmill and Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2). The
      incremental SC test revealed high test-retest reliability for the time to
      exhaustion (ICC = 0.85, typical error [TE] = 0.44, and CV% = 3.88), V'O2peak,
      HRpeak, ventilation, and breathing frequency (ICC = 0.84, 0.72, 0.89, 0.77,
      respectively). The time to exhaustion (r = 0.50, 0.74) of the incremental SC test
      as well as the peak values for V'O2 (r = 0.59, 0.52), HR (r = 0.75, 0.78),
      ventilation (r = 0.57, 0.57), and breathing frequency (r = 0.68, 0.68) were
      significantly correlated (P <= 0.01) with the ramp-like treadmill test and the Yo
      Yo IR2, respectively. The incremental SC test represents a reliable and valid
      method to assess peak values for V'O2 and HR with respect to the specific demand
      of team sport match play by incorporating multidirectional COD movements,
      decision making, and cognitive components.

PMID- 28507166
TI  - Matrix stiffness regulates migration of human lung fibroblasts.
AB  - In patients with pulmonary diseases such as idiopathic pulmonary fibrosis and
      severe acute respiratory distress syndrome, progressive pulmonary fibrosis is
      caused by dysregulated wound healing via activation of fibroblasts after lung
      inflammation or severe damage. Migration of fibroblasts toward the fibrotic
      lesions plays an important role in pulmonary fibrosis. Fibrotic tissue in the
      lung is much stiffer than normal lung tissue. Emerging evidence supports the
      hypothesis that the stiffness of the matrix is not only a consequence of
      fibrosis, but also can induce fibroblast activation. Nevertheless, the effects of
      substrate rigidity on migration of lung fibroblasts have not been fully
      elucidated. We evaluated the effects of substrate stiffness on the morphology,
      alpha-smooth muscle actin (alpha-SMA) expression, and cell migration of primary
      human lung fibroblasts by using polyacrylamide hydrogels with stiffnesses ranging
      from 1 to 50 kPa. Cell motility was assessed by platelet-derived growth factor
      (PDGF)-induced chemotaxis and random walk migration assays. As the stiffness of
      substrates increased, fibroblasts became spindle-shaped and spread. Expression of
      alpha-SMA proteins was higher on the stiffer substrates (25 kPa gel and plastic
      dishes) than on the soft 2 kPa gel. Both PDGF-induced chemotaxis and random walk
      migration of fibroblasts precultured on stiff substrates (25 kPa gel and plastic
      dishes) were significantly higher than those of cells precultured on 2 kPa gel.
      Transfection of the fibroblasts with short interfering RNA for alpha-SMA
      inhibited cell migration. These findings suggest that fibroblast activation
      induced by a stiff matrix is involved in mechanisms of the pathophysiology of
      pulmonary fibrosis.

PMID- 28507168
TI  - Nutritional interventions and the IL-6 response to exercise.
AB  - IL-6 is a pleiotropic cytokine with a wide range of biologic effects. In response
      to prolonged exercise, IL-6 is synthesized by contracting skeletal muscle and
      released into circulation. Circulating IL-6 is thought to maintain energy status
      during exercise by acting as an energy sensor for contracting muscle and
      stimulating glucose production. If tissue damage occurs, immune cells infiltrate
      and secrete cytokines, including IL-6, to repair skeletal muscle damage. With
      adequate rest and nutrition, the IL-6 response to exercise is attenuated as
      skeletal muscle adapts to training. However, sustained elevations in IL-6 due to
      repeated bouts of unaccustomed activities or prolonged exercise with limited rest
      may result in untoward physiologic effects, such as accelerated muscle
      proteolysis and diminished nutrient absorption, and may impair normal adaptive
      responses to training. Recent intervention studies have explored the role of
      mixed meals or carbohydrate, protein, omega-3 fatty acid, or antioxidant
      supplementation in mitigating exercise-induced increases in IL-6. Emerging
      evidence suggests that sufficient energy intake before exercise is an important
      factor in attenuating exercise-induced IL-6 by maintaining muscle glycogen. We
      detail various nutritional interventions that may affect the IL-6 response to
      exercise in healthy human adults and provide recommendations for future research
      exploring the role of IL-6 in the adaptive response to exercise.-Hennigar, S. R.,
      McClung, J. P., Pasiakos, S. M. Nutritional interventions and the IL-6 response
      to exercise.

PMID- 28507167
TI  - Early activation of deleterious molecular pathways in the kidney in experimental
      heart failure with atrial remodeling.
AB  - Heart failure (HF) is a major health problem with worsening outcomes when renal
      impairment is present. Therapeutics for early phase HF may be effective for
      cardiorenal protection, however the detailed characteristics of the kidney in
      early-stage HF (ES-HF), and therefore treatment for potential renal protection,
      are poorly defined. We sought to determine the gene and protein expression
      profiles of specific maladaptive pathways of ES-HF in the kidney and heart.
      Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but
      not ventricular fibrosis, was induced by right ventricular pacing for 10 days.
      Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA)
      tissues from ES-HF versus normal canines (n = 4 of each) were analyzed using RT
      PCR microarrays and protein assays to assess genes and proteins related to
      inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by
      increased circulating natriuretic peptides and components of the renin
      angiotensin-aldosterone system and decreased sodium and water excretion with mild
      renal injury and up-regulation of CNP and renin genes in the kidney. Compared to
      normals, widespread genes, especially genes of the inflammatory pathways, were up
      regulated in KC similar to increases seen in LA Protein expressions related to
      inflammatory cytokines were also augmented in the KC Gene and protein changes
      were less prominent in the LV and KM The ES-HF displayed mild renal injury with
      widespread gene changes and increased inflammatory cytokines. These changes may
      provide important clues into the pathophysiology of ES-HF and for therapeutic
      molecular targets in the kidney of ES-HF.

PMID- 28507169
TI  - Human neutrophil elastase induces endothelial cell apoptosis by activating the
      PERK-CHOP branch of the unfolded protein response.
AB  - Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing
      apoptosis in endothelial cells. Our aim was to investigate the proapoptotic
      mechanism of elastase on endothelial cells and to evaluate the presence of
      elastase in human plaque material. Human endothelial cells were treated with
      purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7
      activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response
      (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein
      kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was
      analyzed by RT-PCR, immunocytochemistry, and Western blot. Genetic silencing of
      CHOP was achieved by small interfering RNA. Elastase induces autophagic-apoptotic
      forms of endothelial cell death in a time- and dose-dependent manner, in
      conjunction with a significant increase in phosphorylation/expression of the
      canonical UPR-activation markers PERK and CHOP. By using CHOP knockdown, we
      identified CHOP as a key mediator of elastase-induced endothelial cell death.
      Immunohistochemical analysis of human rupture-prone plaque specimens confirmed
      the presence of elastase and colocalization with apoptosis. We have demonstrated
      for the first time that the PERK-CHOP branch of the UPR is causally involved in
      elastase-induced apoptosis of endothelial cells. Ex vivo analysis of human
      rupture-prone plaques confirmed the presence of elastase and its colocalization
      with markers of apoptosis. This novel role of elastase underlines the potential
      of combined targeting of elastase and endoplasmic reticulum stress in the
      prevention of plaque progression and cardiovascular events.-Grechowa, I., Horke,
      S., Wallrath, A., Vahl, C.-F., Dorweiler, B. Human neutrophil elastase induces
      endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded
      protein response.

PMID- 28507170
TI  - Hypertension-Causing Mutation in Peroxisome Proliferator-Activated Receptor gamma
      Impairs Nuclear Export of Nuclear Factor-kappaB p65 in Vascular Smooth Muscle.
AB  - Selective expression of dominant negative (DN) peroxisome proliferator-activated
      receptor gamma (PPARgamma) in vascular smooth muscle cells (SMC) results in
      hypertension, atherosclerosis, and increased nuclear factor-kappaB (NF-kappaB)
      target gene expression. Mesenteric SMC were cultured from mice designed to
      conditionally express wild-type (WT) or DN-PPARgamma in response to Cre
      recombinase to determine how SMC PPARgamma regulates expression of NF-kappaB
      target inflammatory genes. SMC-specific overexpression of WT-PPARgamma or agonist
      induced activation of endogenous PPARgamma blunted tumor necrosis factor alpha
      (TNF-alpha)-induced NF-kappaB target gene expression and activity of an NF-kappaB
      responsive promoter. TNF-alpha-induced gene expression responses were enhanced by
      DN-PPARgamma in SMC. Although expression of NF-kappaB p65 was unchanged, nuclear
      export of p65 was accelerated by WT-PPARgamma and prevented by DN-PPARgamma in
      SMC. Leptomycin B, a nuclear export inhibitor, blocked p65 nuclear export and
      inhibited the anti-inflammatory action of PPARgamma. Consistent with a role in
      facilitating p65 nuclear export, WT-PPARgamma coimmunoprecipitated with p65, and
      WT-PPARgamma was also exported from the nucleus after TNF-alpha treatment.
      Conversely, DN-PPARgamma does not bind to p65 and was retained in the nucleus
      after TNF-alpha treatment. Transgenic mice expressing WT-PPARgamma or DN
      PPARgamma specifically in SMC (S-WT or S-DN) were bred with mice expressing
      luciferase controlled by an NF-kappaB-responsive promoter to assess effects on NF
      kappaB activity in whole tissue. TNF-alpha-induced NF-kappaB activity was
      decreased in aorta and carotid artery from S-WT but was increased in vessels from
      S-DN mice. We conclude that SMC PPARgamma blunts expression of proinflammatory
      genes by inhibition of NF-kappaB activity through a mechanism promoting nuclear
      export of p65, which is abolished by DN mutation in PPARgamma.

PMID- 28507173
TI  - Resistant Hypertension: An Update of Experimental and Clinical Findings.

PMID- 28507174
TI  - Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B
      Receptor Signaling in Preeclampsia.
AB  - Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and
      fetal morbidity and mortality. Emerging evidence indicates that global placental
      DNA hypomethylation is observed in patients with preeclampsia and is linked to
      altered gene expression and disease development. However, the molecular basis
      underlying placental epigenetic changes in preeclampsia remains unclear. Using 2
      independent experimental models of preeclampsia, adenosine deaminase-deficient
      mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we
      demonstrate that elevated placental adenosine not only induces hallmark features
      of preeclampsia but also causes placental DNA hypomethylation. The use of genetic
      approaches to express an adenosine deaminase minigene specifically in placentas,
      or adenosine deaminase enzyme replacement therapy, restored placental adenosine
      to normal levels, attenuated preeclampsia features, and abolished placental DNA
      hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73
      (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of
      placental adenosine in the autoantibody-induced preeclampsia mouse model and
      ameliorated preeclampsia features and placental DNA hypomethylation.
      Immunohistochemical studies revealed that elevated placental adenosine-mediated
      DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine
      trophoblasts and that this effect is independent of A2B adenosine receptor
      activation in both preeclampsia models. Extending our mouse findings to humans,
      we used cultured human trophoblasts to demonstrate that adenosine functions
      intracellularly and induces DNA hypomethylation without A2B adenosine receptor
      activation. Altogether, both mouse and human studies reveal novel mechanisms
      underlying placental DNA hypomethylation and potential therapeutic approaches for
      preeclampsia.

PMID- 28507171
TI  - First-in-Man Demonstration of Direct Endothelin-Mediated Natriuresis and
      Diuresis.
AB  - Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in
      chronic kidney disease and resistant hypertension, but their use is complicated
      by sodium and water retention. In animal studies, this side effect arises from
      ETB receptor blockade in the renal tubule. Previous attempts to determine whether
      this mechanism operates in humans have been confounded by the hemodynamic
      consequences of ET receptor stimulation/blockade. We aimed to determine the
      effects of ET signaling on salt transport in the human nephron by administering
      subpressor doses of the ET-1 precursor, big ET-1. We conducted a 2-phase
      randomized, double-blind, placebo-controlled crossover study in 10 healthy
      volunteers. After sodium restriction, subjects received either intravenous
      placebo or big ET-1, in escalating dose (<=300 pmol/min). This increased plasma
      concentration and urinary excretion of ET-1. Big ET-1 reduced heart rate (~8
      beats/min) but did not otherwise affect systemic hemodynamics or glomerular
      filtration rate. Big ET-1 increased the fractional excretion of sodium (from 0.5
      to 1.0%). It also increased free water clearance and tended to increase the
      abundance of the sodium-potassium-chloride cotransporter (NKCC2) in urinary
      extracellular vesicles. Our protocol induced modest increases in circulating and
      urinary ET-1. Sodium and water excretion increased in the absence of significant
      hemodynamic perturbation, supporting a direct action of ET-1 on the renal tubule.
      Our data also suggest that sodium reabsorption is stimulated by ET-1 in the thick
      ascending limb and suppressed in the distal renal tubule. Fluid retention
      associated with ET receptor antagonist therapy may be circumvented by
      coprescribing potassium-sparing diuretics.

PMID- 28507172
TI  - Hemodynamic and Mechanical Properties of the Proximal Aorta in Young and Middle
      Aged Adults With Isolated Systolic Hypertension: The Dallas Heart Study.
AB  - The aim of this study was to assess characteristic impedance (Zc) of the proximal
      aorta in young and middle-aged individuals with isolated systolic hypertension
      (ISH). Zc is an index of aortic stiffness relative to aortic size. In the Dallas
      Heart Study, 2001 untreated participants 18 to 64 years of age (mean age: 42.3
      years; 44% black race) were divided into the following groups based on office
      blood pressure (BP) measurements: (1) optimal BP (systolic BP [SBP] <120 mm Hg
      and diastolic BP [DBP] <80 mm Hg; n=837); (2) prehypertension (SBP 120-139 mm Hg
      and DBP 80-89 mm Hg; n=821); (3) ISH (SBP >=140 mm Hg and DBP <90 mm Hg; n=121);
      (4) isolated diastolic hypertension (SBP <140 mm Hg and DBP >=90 mm Hg; n=44);
      and (5) systolic-diastolic hypertension (SBP >=140 mm Hg and DBP >=90 mm Hg;
      n=178). Zc, aortic arch pulse wave velocity, and minimum ascending aortic size
      were quantified using cardiovascular magnetic resonance. In multivariable
      adjusted linear models, Zc was highest in the ISH group compared with the optimal
      BP, isolated diastolic hypertension, or systolic-diastolic hypertension groups
      (103.2+/-4.0 versus 68.3+/-2.1, 75.4+/-6.0, and 88.9+/-4.8 dyne*seconds/cm5,
      respectively; all P<0.05). The Zc-ISH association did not differ by race. Aortic
      pulse wave velocity was highest in the ISH group compared with the optimal BP,
      isolated diastolic hypertension, or systolic-diastolic hypertension groups (6.3+/
      0.3 versus 4.3+/-0.1, 4.4+/-0.4 and 5.5+/-0.3 m/s, respectively; all P<0.05),
      whereas aortic size was similar across groups (all P>0.2). Results were similar
      in a subgroup of 1551 participants 18 to 49 years of age. In a multiracial
      population-based sample, we found evidence of a mismatch between proximal aortic
      stiffness and diameter in young and middle-aged adults with ISH.

PMID- 28507175
TI  - A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR
      Dependent Mechanism for Stomatal Development.
AB  - The asymmetric cell divisions necessary for stomatal lineage initiation and
      progression in Arabidopsis (Arabidopsis thaliana) require the function of the
      basic helix-loop-helix (bHLH) transcription factor SPEECHLESS (SPCH). Mutants
      lacking SPCH do not produce stomata or lineages. Here, we isolated a new spch-5
      allele carrying a point mutation in the bHLH domain that displayed normal growth,
      but had an extremely low number of sometimes clustered stomata in the leaves,
      whereas the hypocotyls did not have any stomata. In vivo tracking of leaf
      epidermal cell divisions, combined with marker lines and genetic analysis, showed
      that the spch-5 leaf phenotype is dosage dependent and results from the decreased
      ability to initiate and amplify lineages, defects in asymmetric cell fate
      allocation, and misorientation of asymmetric division planes. Notably,
      application of brassinosteroids (BRs) partly rescued the stomatal leaf phenotype
      of spch-5 Transcriptomic analysis combining spch-5 with BR treatments revealed
      that the expression of a set of SPCH target genes was restored by BRs. Our
      results also show that BR-dependent stomata formation and expression of some, but
      not all, SPCH target genes require the integrity of the bHLH domain of SPCH.

PMID- 28507176
TI  - BTS guideline for oxygen use in adults in healthcare and emergency settings.

PMID- 28507177
TI  - Evidence for a Derangement of the Microvascular System in Patients with a Very
      Early Diagnosis of Systemic Sclerosis.
AB  - OBJECTIVE: To investigate whether patients with a very early diagnosis of
      systemic sclerosis (VEDOSS) may already present circulating markers and in vitro
      signs of microvascular dysfunction. METHODS: Serum samples were obtained from 55
      patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched
      healthy controls (HC). Serum levels of pan-vascular endothelial growth factor
      (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal
      microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc,
      VEDOSS, and HC sera. Protein expression of NRP-1 was analyzed by Western
      blotting, cell proliferation by 5'-bromodeoxyuridine assay, migration capacity by
      wound-healing assay, and capillary-like tube formation by Matrigel assay.
      RESULTS: Serum levels of pan-VEGF were increased in patients with VEDOSS and SSc
      versus HC (p = 0.05 and p = 0.003, respectively). Serum levels of sNRP-1 were
      significantly reduced in patients with VEDOSS and SSc compared with controls (p =
      0.012 and p = 0.027, respectively). NRP-1 expression was decreased in H-MVEC
      stimulated with VEDOSS sera (p < 0.001 vs HC). Proliferation was reduced in H
      MVEC stimulated either with VEDOSS or SSc sera in comparison with HC sera (p =
      0.015 and p = 0.043, respectively). Wound healing was compromised in H-MVEC
      stimulated with VEDOSS and SSc sera versus HC sera (p < 0.01 for both).
      Capillarogenesis was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.01)
      and SSc sera (p < 0.001) compared with cells stimulated with HC sera. CONCLUSION:
      Similar to patients with SSc, patients with VEDOSS already present biological
      signs of endothelial dysfunction. Our data demonstrate that VEDOSS sera
      significantly modify endothelial cell behavior and impair the angiogenic
      potential of the microvascular system.

PMID- 28507178
TI  - Anti-carbamylated Protein Antibodies Are Detectable in Various Connective Tissue
      Diseases.
AB  - OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are possible
      diagnostic biomarkers of anticitrullinated protein antibody (ACPA)-negative
      rheumatoid arthritis (RA). We aimed to elucidate the prevalence of anti-CarP
      antibodies in non-RA connective tissue diseases (CTD) because CTD are important
      in the differential diagnosis of ACPA-negative RA. METHODS: The sera from 266
      patients with RA and 616 patients with CTD and 80 healthy controls were examined
      using an in-house anti-CarP ELISA. RESULTS: The prevalence and the level of anti
      CarP antibodies in several CTD were comparable to those in ACPA-negative RA.
      CONCLUSION: Anti-CarP antibodies are not useful for differentiating ACPA-negative
      RA from CTD.

PMID- 28507180
TI  - Outcome Measures Used in Arthroplasty Trials: Systematic Review of the 2008 and
      2013 Literature.
AB  - OBJECTIVE: Previously published literature assessing the reporting of outcome
      measures used in joint replacement randomized controlled trials (RCT) has
      revealed disappointing results. It remains unknown whether international
      initiatives have led to any improvement in the quality of reporting and/or a
      reduction in the heterogeneity of outcome measures used. Our objective was to
      systematically assess and compare primary outcome measures and the risk of bias
      in joint replacement RCT published in 2008 and 2013. METHODS: We searched
      MEDLINE, EMBASE, and CENTRAL for RCT investigating adult patients undergoing
      joint replacement surgery. Two authors independently identified eligible trials,
      extracted data, and assessed risk of bias using the Cochrane tool. RESULTS:
      Seventy RCT (30 in 2008, 40 in 2013) met the eligibility criteria. There was no
      significant difference in the number of trials judged to be at low overall risk
      of bias (n = 6, 20%) in 2008 compared with 2013 [6 (15%); chi-square = 0.302, p =
      0.75]. Significantly more trials published in 2008 did not specify a primary
      outcome measure (n = 25, 83%) compared with 18 trials (45%) in 2013 (chi-square =
      10.6316, p = 0.001). When specified, there was significant heterogeneity in the
      measures used to assess primary outcomes. CONCLUSION: While less than a quarter
      of trials published in both 2008 and 2013 were judged to be at low overall risk
      of bias, significantly more trials published in 2013 specified a primary outcome.
      Although this might represent a temporal trend toward improvement, the overall
      frequency of primary outcome reporting and the wide heterogeneity in primary
      outcomes reported remain suboptimal.

PMID- 28507179
TI  - Elevated Expression of the NLRP3 Inflammasome and Its Correlation with Disease
      Activity in Adult-onset Still Disease.
AB  - OBJECTIVE: The dysregulation of the NLRP3 (NLR containing a pyrin domain)
      inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease
      (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic
      involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in
      AOSD are currently unknown. METHODS: The mRNA expression of NLRP3 inflammasome
      signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD
      and 14 healthy subjects was determined using quantitative-PCR (qPCR). The changes
      in mRNA and protein levels of NLRP3 inflammasome signaling in PBMC treated with
      the potential activator [imiquimod (IMQ)] or inhibitor of NLRP3 were evaluated
      using qPCR and immunoblotting, respectively. The supernatant levels of
      interleukin (IL)-1beta and IL-18 were determined by ELISA. RESULTS: Significantly
      higher mRNA levels of NLRP3 inflammasome signaling were observed in patients with
      AOSD compared with healthy controls. NLRP3 expressions were positively correlated
      with disease activity in patients with AOSD. IMQ (an effective Toll-like receptor
      7 ligand; 10 ug/ml and 25 ug/ml) stimulation of PBMC from patients with AOSD
      induced dose-dependent increases of mRNA expression of NLRP3 (mean +/- standard
      error of the mean, 2.06 +/- 0.46 and 6.05 +/- 1.84, respectively), caspase-1
      (1.81 +/- 0.23 and 4.25 +/- 0.48), IL-1beta (5.68 +/- 1.51 and 12.13 +/- 3.71),
      and IL-18 (2.32 +/- 0.37 and 4.81 +/- 0.51) compared with controls (all p <
      0.005). IMQ stimulation of PBMC from patients similarly induced greater increases
      in protein expressions of NLRP3 inflammasome compared with controls. The protein
      expressions of NLRP3, IL-1beta, and IL-18 on PBMC significantly decreased after
      treatment with NLRP3 inhibitor in patients with AOSD. CONCLUSION: Increased
      expression of NLRP3 inflammasome and its positive correlation with disease
      activity in AOSD suggest its involvement in disease pathogenesis. IMQ upregulated
      expressions of NLRP3 inflammasome signaling, and IMQ might be an activator of
      NLRP3 inflammasome in AOSD.

PMID- 28507181
TI  - Fli1 Deficiency Induces CXCL6 Expression in Dermal Fibroblasts and Endothelial
      Cells, Contributing to the Development of Fibrosis and Vasculopathy in Systemic
      Sclerosis.
AB  - OBJECTIVE: CXCL6, a chemokine with proangiogenic property, is reported to be
      involved in vasculopathy associated with systemic sclerosis (SSc). We
      investigated the contribution of CXCL6 to SSc development by focusing on the
      association of friend leukemia virus integration 1 (Fli1) deficiency, a potential
      predisposing factor of SSc, with CXCL6 expression and clinical correlation of
      serum CXCL6 levels. METHODS: mRNA levels of target genes and the binding of Fli1
      to the CXCL6 promoter were evaluated by quantitative reverse transcription-PCR
      and chromatin immunoprecipitation, respectively. Serum CXCL6 levels were
      determined by ELISA. RESULTS: FLI1 siRNA significantly enhanced CXCL6 mRNA
      expression in human dermal fibroblasts and human dermal microvascular endothelial
      cells, while Fli1 haploinsufficiency significantly suppressed CXCL6 mRNA
      expression in murine peritoneal macrophages stimulated with lipopolysaccharide.
      Supporting a critical role of Fli1 deficiency to induce SSc-like phenotypes,
      CXCL6 mRNA expression was higher in SSc dermal fibroblasts than in normal dermal
      fibroblasts. Importantly, Fli1 bound to the CXCL6 promoter in dermal fibroblasts,
      endothelial cells, and THP-1 cells. In patients with SSc, serum CXCL6 levels
      correlated positively with the severity of dermal and pulmonary fibrosis and were
      elevated in association with cardiac and pulmonary vascular involvement and
      cutaneous vascular symptoms, including Raynaud phenomenon, digital ulcers
      (DU)/pitting scars, and telangiectasia. Especially, serum CXCL6 levels were
      associated with DU/pitting scars and heart involvement by multiple regression
      analysis. CONCLUSION: CXCL6 expression is upregulated by Fli1 deficiency in
      fibroblasts and endothelial cells, potentially contributing to the development of
      fibrosis and vasculopathy in the skin, lung, and heart of SSc.

PMID- 28507182
TI  - Association between Dairy Product Consumption and Incidence of Total Hip
      Arthroplasty for Osteoarthritis.
AB  - OBJECTIVE: The aim of this prospective cohort study was to determine whether
      dairy product consumption was associated with the incidence of total hip
      arthroplasty for osteoarthritis (OA). METHODS: There were 38,924 participants
      from the Melbourne Collaborative Cohort Study who had dairy product consumption
      recorded in 1990-1994. The incidence of total hip arthroplasty for OA during 2001
      2013 was determined by linking cohort records to the Australian Orthopaedic
      Association National Joint Replacement Registry. RESULTS: Over an average of 11.8
      years of followup, 1505 total hip arthroplasties for OA were identified (524 in
      men, 981 in women). In men, a 1 SD increase in dairy product consumption was
      associated with a 21% increased incidence of total hip arthroplasty for OA (HR
      1.21, 95% CI 1.10-1.33), with a dose-response relationship observed for quartiles
      of dairy product consumption (p for trend = 0.001). These results were
      independent of age, body mass index, country of birth, education, smoking status,
      vigorous physical activity, calcium supplementation, energy consumption,
      circulating 25-hydroxy vitamin D, hypertension, and diabetes. No significant
      association was observed for women (HR 1.02, 95% CI 0.95-1.09). CONCLUSION:
      Increasing dairy product consumption was associated with an increased risk of
      total hip arthroplasty for men with OA, with no significant association observed
      for women. Understanding the mechanisms may help identify strategies to prevent
      hip OA, particularly for men.

PMID- 28507183
TI  - Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive
      Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with
      Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with an increased
      risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin
      (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the
      effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy
      of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE.
      METHODS: Patients consecutively admitted to our center who, at admission,
      satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus
      Collaborating Clinics classification criteria for SLE, and had not experienced
      any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c
      HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ
      associated with a lower incidence of CVE. Cox regression analysis served to
      identify factors associated with a first CVE. RESULTS: For the study, 189
      patients with SLE were enrolled and monitored for 13 years (median). Ten CVE
      occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher
      in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at
      least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g
      (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that
      antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047,
      respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR
      18.054) increased the risk of a first CVE. CONCLUSION: Our results suggest that
      prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional
      evidence for its continued use in patients with SLE.

PMID- 28507184
TI  - Importance of Obtaining Remission for Work Productivity and Activity of Patients
      with Rheumatoid Arthritis.
AB  - OBJECTIVE: To identify the factors relevant to work and activity impairment in
      patients with rheumatoid arthritis. METHODS: In total, 1274 consecutive patients
      were included. Work and activity impairment were measured by the Work
      Productivity and Activity Impairment questionnaire, and related clinical factors
      were examined. RESULTS: Work and activity impairment was reported by 67.4% of the
      patients. Multivariable linear regression analyses revealed pain and non
      remission to be associated with activity impairment and presenteeism. Patients in
      remission had significantly less activity impairment and presenteeism than those
      with low disease activity. CONCLUSION: Remission achievement is essential for
      ensuring work performance and activity.

PMID- 28507186
TI  - Zygapophyseal Joint Fusion in Ankylosing Spondylitis Assessed by Computed
      Tomography: Associations with Syndesmophytes and Spinal Motion.
AB  - OBJECTIVE: Because zygapophyseal joints (ZJ) are difficult to visualize on
      radiographs, little is known about the relationship of ZJ fusion to other
      features of spinal damage in ankylosing spondylitis (AS). We used computed
      tomography (CT) to investigate the concordance of ZJ fusion and syndesmophytes,
      and examined the contribution of both features to spinal motion. METHODS: We
      performed thoracolumbar CT scans (T10-T11 to L3-L4) on 55 patients. Two readers
      scored scans for ZJ fusion, which were compared to syndesmophyte height and
      extent of bridging, measured by computer algorithm at the same levels. We used
      multiple regression analysis to evaluate the relative contributions of ZJ fusion
      and syndesmophytes to spinal mobility. RESULTS: Fifty-one percent of patients had
      ZJ fusion in at least 1 vertebral level. Fusion was present in 129 of 652
      individual ZJ. Syndesmophytes and bridging were often present in vertebral levels
      without ZJ fusion, suggesting that syndesmophytes most often develop first. ZJ
      fusion was present in 34% of vertebral levels with syndesmophytes and 55.9% of
      levels with bridging, suggesting a closer association with bridging.
      Syndesmophytes and ZJ fusion had similar associations with the modified Schober
      test, but syndesmophytes were more strongly associated with limitations in
      lateral thoracolumbar flexion. ZJ rarely showed new fusion over 4 years.
      CONCLUSION: Thoracolumbar ZJ fusion in AS is rarely present at vertebral levels
      without syndesmophytes. Syndesmophytes, therefore, likely appear before ZJ fusion
      at a given vertebral level. Both syndesmophytes and ZJ fusion contribute to
      limited forward lumbar flexion, but syndesmophytes contribute more to limited
      lateral flexion.

PMID- 28507185
TI  - The OMERACT First-time Participant Program: Fresh Eye from the New Guys.
AB  - OBJECTIVE: To describe the experience of the first-time participant (newbie)
      training program at the Outcome Measures in Rheumatology (OMERACT) 2016 meeting.
      METHODS: We conducted new participant sessions at OMERACT 2016, including a 2-h
      introductory session on Day 1 followed by 1-h evening followup sessions on days 1
      4. Pre- and post-meeting surveys assessed participants' levels of comfort with
      the principles of the OMERACT Filter 2.0 (the essential tools for OMERACT
      methodology) and the different types of OMERACT sessions, and whether
      participants felt welcome. In addition, on the final day, a nominal group
      technique was used to elicit problematic components of the meeting and to develop
      solutions to those problems. RESULTS: Of the 43 new attendees, 38 participated in
      the introductory session and 14-18 attended the followup sessions. Comparing Day
      1 (preintroductory session) to days 1-3 (post), a similar proportion understood
      different types of sessions extremely well [45% (pre) versus 47%, 44%, and 36%
      (post), respectively], and a higher proportion understood principles of the
      OMERACT filter extremely well [22% (pre) versus 55%, 44%, and 40% (post),
      respectively]. Most reported feeling welcome (86.7%) and felt they contributed to
      breakout sessions (93.3%) on the evening of Day 1; results were sustained on days
      2-3. The most commonly reported "best" experience included the OMERACT culture
      and the most common reported experience needing improvement included facilitation
      issues during breakouts. CONCLUSION: The first-time participants came to OMERACT
      2016 with a high baseline level of understanding. They rapidly attained a high
      comfort level with participation and provided concrete and innovative solutions
      to the most commonly reported experiences needing improvement.

PMID- 28507187
TI  - Measuring Disease Exacerbation and Flares in Rheumatoid Arthritis: Comparison of
      Commonly Used Disease Activity Indices and Individual Measures.
AB  - OBJECTIVE: To evaluate and compare the utility of commonly used outcome measures
      for assessing disease exacerbation or flare in patients with rheumatoid arthritis
      (RA). METHODS: Data from the Dutch Potential Optimalisation of (Expediency) and
      Effectiveness of Tumor necrosis factor-alpha blockers (POET) study, in which 462
      patients discontinued their tumor necrosis factor-alpha inhibitor, were used. The
      ability of different measures to discriminate between those with and without
      physician-reported flare or medication escalation at the 3-month visit (T2) was
      evaluated by calculating effect size (ES) statistics. Responsiveness to increased
      disease activity was compared between measures by standardizing change scores
      (SCS) from baseline to the 3-month visit. Finally, the incremental validity of
      individual outcome measures beyond the Simplified Disease Activity Score was
      evaluated using logistic regression analysis. RESULTS: The SCS were greater for
      disease activity indices than for any of the individual measures. The 28-joint
      Disease Activity Score, Clinical Disease Activity Index, and Simplified Disease
      Activity Index performed similarly. Pain and physician's (PGA) and patient's
      global assessment (PtGA) of disease activity were the most responsive individual
      measures. Similar results were obtained for discriminative ability, with greatest
      ES for disease activity indices followed by pain, PGA, and PtGA. Pain was the
      only measure to demonstrate incremental validity beyond SDAI in predicting 3
      month flare status. CONCLUSION: These results support the use of composite
      disease activity indices, patient-reported pain and disease activity, and
      physician-reported disease activity for measuring disease exacerbation or
      identifying flares of RA. Physical function, acute-phase response, and the
      auxiliary measures fatigue, participation, and emotional well-being performed
      poorly.

PMID- 28507188
TI  - Cryoglobulinemia in Sjogren Syndrome: A Disease Subset that Links Higher Systemic
      Disease Activity, Autoimmunity, and Local B Cell Proliferation in Mucosa
      associated Lymphoid Tissue.
AB  - OBJECTIVE: To compare systemic disease activity by validated tools, i.e., the
      European League Against Rheumatism Sjogren Syndrome Disease Activity Index
      (ESSDAI) and the Clinical ESSDAI (ClinESSDAI) scores, between primary Sjogren
      syndrome (pSS) with positive serum cryoglobulins and pSS without serum
      cryoglobulins. METHODS: There were 825 consecutive patients with pSS who were
      retrospectively evaluated. RESULTS: The ESSDAI and the ClinESSDAI scores were
      significantly higher in cryoglobulin-positive patients (p < 0.0001, for both
      scores). Cryoglobulinemia was significantly associated with these domains:
      constitutional (p = 0.003), lymphadenopathy (p = 0.007), glandular (p = 0.0002),
      cutaneous (p < 0.0001), peripheral nervous system (p < 0.0001), hematological (p
      = 0.004), and biological (p < 0.0001). CONCLUSION: Cryoglobulin-positive patients
      show the highest systemic activity in pSS.

PMID- 28507189
TI  - Oxidative stress affects sperm performance and ejaculate redox status in
      subordinate house sparrows.
AB  - Oxidative stress is the result of random cellular damage caused by reactive
      oxygen species that leads to cell death, ageing or illness. Most physiological
      processes can result in oxidative stress, which in turn has been identified as a
      major cause of infertility. In promiscuous species, the fertilizing ability of
      the ejaculate partly determines the male reproductive success. When dominance
      determines access to fertile females, theory predicts that lower ranking males
      should increase resource investment into enhancing ejaculate quality. We
      hypothesized that subordinate males should thus prioritize antioxidant protection
      of their ejaculates to protect them from oxidative stress. We put this hypothesis
      to the test by chronically dosing wild house sparrows with diquat (~1 mg kg-1), a
      herbicide that increases pro-oxidant generation. We found that, although they
      increased their antioxidant levels in the ejaculate, diquat-treated males
      produced sperm with reduced velocity. Importantly, and contrary to our
      hypothesis, males at the bottom of the hierarchy suffered the largest reduction
      in sperm velocity. We suggest that resource access hinders individuals' ability
      to cope with environmental hazards. Our results point at oxidative stress as a
      likely physiological mechanism mediating ejaculate quality, while individual
      ability to access resources may play a role in constraining the extent to which
      such resources can be allocated into the ejaculate.

PMID- 28507190
TI  - The effect of thermal acclimation on aerobic scope and critical swimming speed in
      Atlantic salmon, Salmo salar.
AB  - The Atlantic salmon is extensively studied owing to conservation concerns and its
      economic importance in aquaculture. However, a thorough report of their aerobic
      capacity throughout their entire thermal niche has not been described. In this
      study, Atlantic salmon (~450 g) were acclimated for 4 weeks at 3, 8, 13, 18 or 23
      degrees C, and then tested in a large Brett-type swimming respirometer in groups
      of 10 per trial. Both standard metabolic rate and active metabolic rate continued
      to increase with temperature, which resulted in an aerobic scope that also
      increased with temperature, but was statistically similar between 13, 18 and 23
      degrees C. The critical swimming speed peaked at 18 degrees C (93.1+/-1.2 cm s
      1), and decreased significantly at the extreme temperatures to 74.8+/-0.5 and
      84.8+/-1.6 cm s-1 at 3 and 23 degrees C, respectively. At 23 degrees C, the
      accumulated mortality reached 20% over 4 weeks, while no fish died during
      acclimation at colder temperatures. Furthermore, fish at 23 degrees C had poor
      appetite and lower condition factor despite still having a high aerobic scope,
      suggesting that oxygen uptake was not the limiting factor in the upper thermal
      niche boundary. In conclusion, Atlantic salmon were able to maintain a high
      aerobic capacity and good swimming capabilities throughout the entire thermal
      interval tested, thus demonstrating a high level of flexibility in respiratory
      capacity towards different temperature exposures.

PMID- 28507191
TI  - Lowering metabolic rate mitigates muscle atrophy in western fence lizards.
AB  - Extended periods of skeletal muscle disuse can cause a significant loss of
      contractile proteins, which compromises the ability to generate force, mechanical
      work or power, thus compromising locomotor performance. Several hibernating
      organisms can resist muscle atrophy despite months of inactivity. This resistance
      has been attributed to a reduction in body temperature and metabolic rate and
      activation of physiological pathways that counteract pathways of protein
      degradation. However, in these systems, such strategies are not mutually
      exclusive and the effects of these mechanisms can be difficult to separate. In
      this study, we used the western fence lizard, Sceloporus occidentalis, as an
      ectothermic model to determine whether a reduction in metabolic rate is
      sufficient to resist muscle atrophy. We induced atrophy through sciatic
      denervation of the gastrocnemius muscle and housed lizards at either 15 or 30
      degrees C for 6-7 weeks. Following treatment, we used muscle ergometry to measure
      maximum isometric force, the force-velocity relationship and contractile dynamics
      in the gastrocnemius. This approach allowed us to relate changes in the size and
      morphology to functional metrics of contractile performance. A subset of samples
      was used to histologically determine muscle fiber types. At 30 degrees C,
      denervated muscles had a larger reduction in muscle mass, physiological cross
      sectional area and maximum isometric force than at 15 degrees C. Maximum
      shortening velocity of the muscle decreased slightly in animals housed at 30
      degrees C but did not change in those housed at 15 degrees C. Our results suggest
      that metabolic rate alone can influence the rate of muscle atrophy and that
      ectothermic vertebrates may have an intrinsic mechanism to resist muscle atrophy
      during seasonal periods of inactivity.

PMID- 28507192
TI  - Performance Fatigability: Mechanisms and Task Specificity.
AB  - Performance fatigability is characterized as an acute decline in motor
      performance caused by an exercise-induced reduction in force or power of the
      involved muscles. Multiple mechanisms contribute to performance fatigability and
      originate from neural and muscular processes, with the task demands dictating the
      mechanisms. This review highlights that (1) inadequate activation of the
      motoneuron pool can contribute to performance fatigability, and (2) the demands
      of the task and the physiological characteristics of the population assessed,
      dictate fatigability and the involved mechanisms. Examples of task and population
      differences in fatigability highlighted in this review include contraction
      intensity and velocity, stability and support provided to the fatiguing limb, sex
      differences, and aging. A future challenge is to define specific mechanisms of
      fatigability and to translate these findings to real-world performance and
      exercise training in healthy and clinical populations across the life span.

PMID- 28507193
TI  - Current and Future Prospects for Preventing Malaria Transmission via the Use of
      Insecticides.
AB  - Malaria vectors have developed resistance to all classes of insecticides that are
      used to target the adult mosquito to prevent parasite transmission. The number of
      resistant mosquito populations has increased dramatically in recent years, most
      likely as a result of the scale-up of vector control activities, and the
      intensity of this resistance is increasing rapidly and compromising the
      performance of vector control tools. Bednets and indoor residual spray
      formulations containing alternative active ingredients have shown promise in
      field trials but are still several years away from implementation. As existing
      insecticides become less effective at killing mosquitoes in the countries with
      the highest burden of malaria, there is growing concern that the advances made in
      reducing malaria transmission will be eroded by insecticide resistance. The
      likelihood of this scenario, and strategies that may help mitigate against this,
      are reviewed below.

PMID- 28507194
TI  - Molecular Basis of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis:
      Historical Advances, Current Knowledge, and Future Challenges.
AB  - We provide an overview of groundbreaking studies that laid the foundation for our
      current understanding of exercise-induced mitochondrial biogenesis and its
      contribution to human skeletal muscle fitness. We highlight the mechanisms by
      which skeletal muscle responds to the acute perturbations in cellular energy
      homeostasis evoked by a single bout of endurance-based exercise and the
      adaptations resulting from the repeated demands of exercise training that
      ultimately promote mitochondrial biogenesis through hormetic feedback loops.
      Despite intense research efforts to elucidate the cellular mechanisms
      underpinning mitochondrial biogenesis in skeletal muscle, translating this basic
      knowledge into improved metabolic health at the population level remains a future
      challenge.

PMID- 28507196
TI  - Health Benefits of Exercise.
AB  - Overwhelming evidence exists that lifelong exercise is associated with a longer
      health span, delaying the onset of 40 chronic conditions/diseases. What is
      beginning to be learned is the molecular mechanisms by which exercise sustains
      and improves quality of life. The current review begins with two short
      considerations. The first short presentation concerns the effects of endurance
      exercise training on cardiovascular fitness, and how it relates to improved
      health outcomes. The second short section contemplates emerging molecular
      connections from endurance training to mental health. Finally, approximately half
      of the remaining review concentrates on the relationships between type 2
      diabetes, mitochondria, and endurance training. It is now clear that physical
      training is complex biology, invoking polygenic interactions within cells,
      tissues/organs, systems, with remarkable cross talk occurring among the former
      list.

PMID- 28507195
TI  - Molecular Signaling Involved in Entry and Exit of Malaria Parasites from Host
      Erythrocytes.
AB  - During the blood stage, Plasmodium spp. merozoites invade host red blood cells
      (RBCs), multiply, exit, and reinvade uninfected RBCs in a continuing cycle that
      is responsible for all the clinical symptoms associated with malaria. Entry into
      (invasion) and exit from (egress) RBCs are highly regulated processes that are
      mediated by an array of parasite proteins with specific functional roles. Many of
      these parasite proteins are stored in specialized apical secretory vesicles, and
      their timely release is critical for successful invasion and egress. For example,
      the discharge of parasite protein ligands to the apical surface of merozoites is
      required for interaction with host receptors to mediate invasion, and the timely
      discharge of proteases and pore-forming proteins helps in permeabilization and
      dismantling of limiting membranes during egress. This review focuses on our
      understanding of the signaling mechanisms that regulate apical organelle
      secretion during host cell invasion and egress by malaria parasites. The review
      also explores how understanding key signaling mechanisms in the parasite can open
      opportunities to develop novel strategies to target Plasmodium parasites and
      eliminate malaria.

PMID- 28507197
TI  - Muscle-Adipose Tissue Cross Talk.
AB  - Exercise training results in adaptations to both skeletal muscle and white
      adipose tissue (WAT) and protects against metabolic disorders including obesity
      and type 2 diabetes. Exercise-induced adaptations include an altered profile of
      secreted proteins, both myokines (from skeletal muscle) and adipokines (from
      adipose tissue). These secreted proteins may act in an endocrine manner to
      facilitate tissue-to-tissue communication and "cross talk," likely working
      together to improve overall metabolic health. Some studies suggest that
      contracting skeletal muscles release myokines that may function to alter the
      phenotype of WAT, including WAT "beiging," in which there is increased expression
      of beige marker genes and increased presence of multilocular cells within the
      WAT.

PMID- 28507198
TI  - Modern Vector Control.
AB  - The rapid spread of mosquito resistance to currently available insecticides, and
      the current lack of an efficacious malaria vaccine are among many challenges that
      affect large-scale efforts for malaria control. As goals of malaria elimination
      and eradication are put forth, new vector-control paradigms and tools and/or
      further optimization of current vector-control products are required to meet
      public health demands. Vector control remains the most effective measure to
      prevent malaria transmission and present gains against malaria mortality and
      morbidity may be maintained as long as vector-intervention strategies are
      sustained and adapted to underlying vector-related transmission dynamics. The
      following provides a brief overview of vector-control strategies and tools either
      in use or under development and evaluation that are intended to exploit key
      entomological parameters toward driving down transmission.

PMID- 28507199
TI  - Whole body vibration exercise combined with an extract of Coriandrum sativum
      modify some biochemical/physiological parameters in rats.
AB  - The aim of the present study was to evaluate the effect of the association of
      whole body vibration (WBV) exercise with an aqueous extract of coriander on the
      biodistribution of the radiopharmaceutical sodium pertechnetate, on the
      concentration of some plasma biomarker, on the feed intake, on the body mass, and
      on the stool consistency in rats. Rats were divided in four groups and submitted
      to different treatments for 40 days. The control group (CON) received deionized
      water. The group treated with coriander (COR) received the extract of coriander.
      The rats that were exposed to WBV exercises (WBV-E) also received deionized
      water. A group of animals received coriander and was exposed to WBV (COR + WBV
      E). We found in testis a decrease (0.13 +/- 0.01 to 0.06 +/- 0.03) of the
      percentages of injected radioactivity per gram (%ATI/g) in the WBV-E in
      comparison with the COR. There is no significant alteration on the concentrations
      of the plasma biomarkers. The feed intake showed a statistically significant
      increase in WBV-E. No significant difference on the body mass was found. The
      stool analysis showed a statistical difference on the consistency between COR
      (hard and dry, darker) and all the other groups (normal). In conclusion, it was
      verified that possible modifications in some biochemical/physiological parameters
      of the rats submitted to WBV exercise would be capable to increase the feed
      intake without changing the body mass, and normalizing the stool consistency
      altered by the coriander supplementation. Further studies are needed to try to
      understand better the biological effects involving the association of WBV
      exercise and coriander.

PMID- 28507200
TI  - Effects of microvirin monomers and oligomers on hepatitis C virus.
AB  - Microvirin (MVN) is a carbohydrate-binding protein which shows high specificity
      for high-mannose type N-glycan structures. In the present study, we tried to
      identify whether MVN could bind to high-mannose containing hepatitis C virus
      (HCV) envelope glycoproteins, which are heavily decorated high-mannose glycans.
      In addition, recombinantly expressed MVN oligomers in di-, tri- and tetrameric
      form were evaluated for their viral inhibition. MVN oligomers bound more
      efficiently to HCV virions, and displayed in comparison with the MVN monomer a
      higher neutralization potency against HCV infection. The antiviral effect was
      furthermore affected by the peptide linker sequence connecting the MVN monomers.
      The results indicate that MVN oligomers such as trimers and tetramers may be used
      as future neutralization agents against HCV infections.

PMID- 28507201
TI  - Sensitivity of non-small cell lung cancer to erlotinib is regulated by the
      Notch/miR-223/FBXW7 pathway.
AB  - Recent evidence supports a role for microRNA-223 (miR-223) in modulating tumor
      cell sensitivity to chemotherapeutic drugs; however, its role in cellular
      resistance to the effects of epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs) used in treatment of non-small cell lung cancer (NSCLC)
      remains to be elucidated. The levels of miR-223 in parental cell line (HCC827)
      and erlotinib resistant HCC827 cell line (HCC827/ER) were detected by qRT-PCR.
      HCC827/ER cells were treated with MK-2206 to block the Akt signaling pathway or
      RO4929097 to block the Notch signaling pathway, and then transfected with an miR
      223 inhibitor or interference expression plasmid of F-Box/WD repeat-containing
      protein 7 (FBXW7) or insulin-like growth factor 1 receptor (IGF1R). HCC827 cells
      were transfected with miR-223 mimics. Next, CCK-8, colony formation, and flow
      cytometric apoptosis assays were used to assess cell resistance to erlotinib.
      When compared with its expression in HCC827 cells, miR-223 expression was
      significantly up-regulated in HCC827/ER cells. Blocking either the Akt or Notch
      signaling pathway and reducing miR-223 expression resulted in decreased
      resistance in HCC827/ER cells. Conversely, increasing miR-223 expression induced
      cell resistance to erlotinib in HCC827 cells. miR-223 enhanced resistance to
      erlotinib by down-regulating FBXW7 expression. Reducing FBXW7 expression lowered
      resistance to erlotinib in HCC827/ER cells, while interference with expression of
      IGF1R produced no significant effect. This study demonstrated that NSCLC cells
      can up-regulate their levels of miR-223 expression via the Akt and Notch
      signaling pathways. miR-223 may serve as an important regulator of erlotinib
      sensitivity in NSCLC cells by targeting FBXW7.

PMID- 28507202
TI  - Determination of volatile organic compounds exhaled by cell lines derived from
      hematological malignancies.
AB  - : Background: The gas human exhaled contains many volatile organic compounds
      (VOCs), which is related to the health status of body. Analysis of VOCs has been
      proposed as a noninvasive diagnostic tool for certain cancers. Detailed research
      on the VOCs in gas exhaled by cell can characterize cell type specific
      metabolites and may be helpful to detect the cancer markers in clinical
      practice.Methods: Solid-phase microextraction (SPME) gas chromatography-mass
      spectrometry was used to detect VOCs in the headspace of tissue culture flask in
      non-Hodgkin's lymphoma (NHL) cell line JEKO and acute mononuclear leukemia cell
      line SHI-1, to elaborate the characteristic gaseous biomarkers of hematological
      malignancies. While macrophage cells and lymphocytic cells were acted as control.
      The blank group was only the RPMI 1640 medium containing 10% fetal calf serum
      that without cells.Results: Comparing with control group, the concentration of
      dimethyl sulfide, 2,4-dimethylheptane, methylbenzene, o-xylene, dodecane, and 1,3
      di-tert-butylbenzene in JEKO cells was relatively higher, while the concentration
      of ethanol, hexanal, and benzaldehyde was lower. In SHI-1 cells, the levels of
      2,4-dimethylheptane, benzene, 4-methyldecane, chloroform, 3,7-dimethyl dodecane,
      and hexadecane were significantly elevated, but the levels of hexanol and
      cyclohexanol were distinctly reduced. CONCLUSIONS: This pilot study revealed that
      the malignant hematological cells could change the components of VOCs in the cell
      culture flask in a cell type-specific pattern. The traits of VOCs in our setting
      offered new strategy for hematological malignancies tracing, and would act as
      potential biomarkers in diagnosis of malignant hematological diseases.

PMID- 28507203
TI  - Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and
      Emerging Therapeutic Options.
AB  - : Advances in the field of cancer immunotherapy have occurred rapidly over the
      past decade. Exciting results from clinical trials have led to new treatment
      options and improved survival for patients with a myriad of solid tumor
      pathologies. However, questions remain unanswered regarding duration and timing
      of therapy, combination regimens, appropriate biomarkers of disease, and optimal
      monitoring of therapeutic response. This article reviews emerging
      immunotherapeutic agents and significant clinical trials that have led to
      advancements in the field of immuno-oncology for patients with head and neck
      squamous cell carcinoma. IMPLICATIONS FOR PRACTICE: This review article
      summarizes recently developed agents that harness the immune system to fight head
      and neck squamous cell carcinoma. A brief review of the immune system and its
      role in cancer development is included. Recently completed and emerging
      therapeutic trials centering on the immune system and head and neck cancer are
      reviewed.

PMID- 28507204
TI  - Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture-Based Assay
      of Circulating Tumor DNA.
AB  - : ALK rearrangements have been observed in 0.05%-2.5% of patients with colorectal
      cancers (CRCs) and are predicted to be oncogenic drivers largely mutually
      exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a
      patient with metastatic CRC who was treatment naive at the time of molecular
      testing. Initial ALK immunohistochemistry (IHC) staining was negative, but
      parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using
      similar hybrid capture-based assays each identified an identical STRN-ALK fusion.
      Subsequent ALK IHC staining of the same specimens was positive, suggesting that
      the initial result was a false negative. This report is the first instance of an
      ALK fusion in CRC detected using a ctDNA assay. KEY POINTS: Current guidelines
      for colorectal cancer (CRC) only recommend genomic assessment of KRAS, NRAS,
      BRAF, and microsatellite instability (MSI) status.ALK rearrangements are rare in
      CRC, but patients with activating ALK fusions have responded to targeted
      therapiesALK rearrangements can be detected by genomic profiling of ctDNA from
      blood or tissue, and this methodology may be informative in cases where
      immunohistochemistry (IHC) or other standard testing is negative.

PMID- 28507209
TI  - In This Issue of Diabetes.

PMID- 28507207
TI  - Role of osteocytes in mediating bone mineralization during hyperhomocysteinemia.
AB  - Hyperhomocysteinemia (HHCY) is a risk factor for osteoporosis but whether HHCY
      affects bone mineralization or not is still ambiguous. Herein we evaluated
      whether homocysteine affects tissue mineral density (TMD) of cortical bone and if
      so the role of osteocytes. CD1 mice administered with homocysteine (5 mg/100 g
      body weight, i.p.) for 7, 15 and 30 days showed temporal changes in TMD and
      osteocyte lacunar density in femoral cortices. Short-term administration of
      homocysteine (day 7) increased osteocyte lacunar density and reduced TMD
      evidenced by microCT50 while prolonged administration of homocysteine (day 30)
      reinstated TMD and lacunar density to baseline values. Major differences were
      decreased number of nucleated osteocyte lacunae, increased number of empty
      lacunae and cleaved caspase 3-positive osteocyte lacunae in day 30 HHCY bone
      evidenced by H&E staining and immunohistochemistry. Other differences were
      induction in mineralization genes like Dmp1, Phex and Sost in cortical bone by
      real-time PCR and increased number of Dmp1- and Sost-positive osteocyte lacunae
      in day 30 HHCY bone evidenced by immunohistochemistry. Both HHCY day 7 and day 30
      samples showed reduced Young's modulus demonstrating that biomechanical property
      of bone was lost during early HHCY itself, which did not improve with recovery of
      TMD. Our results thus demonstrate occurrence of two phases in cortical bone upon
      HHCY: the early phase that involved loss of TMD and increase in osteocyte numbers
      and a late phase that involved osteocyte reprogramming, apoptosis and
      mineralization, which reinstated TMD but compromised biomechanical property. To
      conclude, osteocytes have a potential role in arbitrating bone pathogenesis
      during HHCY.

PMID- 28507205
TI  - A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and
      Diffuse Brain Metastases.
AB  - : A challenge in precision medicine requires identification of actionable driver
      mutations. Critical to such effort is the deployment of sensitive and well
      validated assays for mutation detection. Although identification of such
      alterations within the tumor tissue remains the gold standard, many advanced non
      small cell lung cancer cases have only limited tissue samples, derived from small
      biopsies or fine-needle aspirates, available for testing. More recently,
      noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA)
      have become an alternative method for identifying molecular biomarkers and
      screening patients eligible for targeted therapies. In this article, we present a
      case of a 52-year-old never-smoking male who presented with widely metastatic
      atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping
      using DNA harvested from a bone metastasis was unsuccessful due to limited
      material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical
      significance of the mutation in this particular cancer type and therapeutic
      strategies are discussed. KEY POINTS: To our knowledge, this index case
      represents the first reported ALK translocation identified in an atypical
      carcinoid tumor.Liquid biopsy such as circulating tumor DNA is a feasible
      alternative platform for identifying sensitizing genomic alterations.Second
      generation ALK inhibitors represent a new paradigm for treating ALK-positive
      patients with brain metastases.

PMID- 28507206
TI  - Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation
      Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line
      Gefitinib.
AB  - BACKGROUND: This study aimed to identify independent prognostic factors for
      overall survival (OS) of patients with advanced non-small cell lung cancer
      (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation
      and receiving gefitinib as first-line treatment in real-world practice. MATERIALS
      AND METHODS: We enrolled 226 patients from June 2011 to May 2013. During this
      period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the
      Bureau of National Health Insurance of Taiwan. RESULTS: The median progression
      free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7
      14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards
      regression model revealed that postoperative recurrence, performance status
      (Eastern Cooperative Oncology Grade [ECOG] >=2), smoking index (>=20 pack-years),
      liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV)
      infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3
      [0.11-0.83], p = .02; 2.69 [1.60-4.51], p < .001; 1.92 [1.24-2.97], p = .003;
      2.26 [1.34-3.82], p = .002; 3.38 [1.85-7.78], p < .001, respectively). However,
      brain metastasis (BM) at initial diagnosis or intracranial progression during
      gefitinib treatment had no impact on OS (1.266 [0.83-1.93], p = .275 and 0.75
      [0.48-1.19], p = .211, respectively). CONCLUSION: HCV infection, performance
      status (ECOG >=2), newly diagnosed advanced NSCLC without prior operation, and
      liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC
      patients treated with first-line gefitinib; however, neither BM at initial
      diagnosis nor intracranial progression during gefitinib treatment had an impact
      on OS. IMPLICATIONS FOR PRACTICE: The finding that chronic hepatitis C virus
      (HCV) infection might predict poor overall survival (OS) in epidermal growth
      factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC)
      patients treated with first-line gefitinib may raise awareness of benefit from
      anti-HCV treatment in this patient population. Brain metastasis in the initial
      diagnosis or intracranial progression during gefitinib treatment is not a
      prognostic factor for OS. This study, which enrolled a real-world population of
      NSCLC patients, including sicker patients who were not eligible for a clinical
      trial, may have impact on guiding usual clinical practice.

PMID- 28507211
TI  - Autologous Pluripotent Stem Cell-Derived beta-Like Cells for Diabetes Cellular
      Therapy.
AB  - Development of stem cell technologies for cell replacement therapy has progressed
      rapidly in recent years. Diabetes has long been seen as one of the first
      applications for stem cell-derived cells because of the loss of only a single
      cell type-the insulin-producing beta-cell. Recent reports have detailed
      strategies that overcome prior hurdles to generate functional beta-like cells
      from human pluripotent stem cells in vitro, including from human induced
      pluripotent stem cells (hiPSCs). Even with this accomplishment, addressing
      immunological barriers to transplantation remains a major challenge for the
      field. The development of clinically relevant hiPSC derivation methods from
      patients and demonstration that these cells can be differentiated into beta-like
      cells presents a new opportunity to treat diabetes without immunosuppression or
      immunoprotective encapsulation or with only targeted protection from
      autoimmunity. This review focuses on the current status in generating and
      transplanting autologous beta-cells for diabetes cell therapy, highlighting the
      unique advantages and challenges of this approach.

PMID- 28507210
TI  - Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer.
AB  - The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC)
      are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic
      cancer, but increasing epidemiological data point to PDAC as also a cause of
      diabetes due to unknown mechanisms. New-onset diabetes is of particular interest
      to the oncology community as the differentiation of new-onset diabetes caused by
      PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address
      these relationships and raise awareness of the relationships between PDAC and
      diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic
      Cancer was held at the American Diabetes Association's 76th Scientific Sessions
      in June 2016. This article summarizes the data presented at that symposium,
      describing the current understanding of the interrelationships between diabetes,
      diabetes management, and pancreatic cancer, and identifies areas where additional
      research is needed.

PMID- 28507212
TI  - Adiponectin and beta-Cell Adaptation in Pregnancy.

PMID- 28507213
TI  - Postprandial Suppression of Glucagon Secretion: A Puzzlement.

PMID- 28507215
TI  - Comment on Adam et al. Metformin Effect on Nontargeted Metabolite Profiles in
      Patients With Type 2 Diabetes and in Multiple Murine Tissues. Diabetes
      2016;65:3776-3785.

PMID- 28507216
TI  - Response to Comment on Adam et al. Metformin Effect on Nontargeted Metabolite
      Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues.
      Diabetes 2016;65:3776-3785.

PMID- 28507217
TI  - Comment on Ussar et al. Regulation of Glucose Uptake and Enteroendocrine Function
      by the Intestinal Epithelial Insulin Receptor. Diabetes 2017;66:886-896.

PMID- 28507218
TI  - Response to Comment on Ussar et al. Regulation of Glucose Uptake and
      Enteroendocrine Function by the Intestinal Epithelial Insulin Receptor. Diabetes
      2017;66:886-896.

PMID- 28507220
TI  - Celebrating 35 Years of the AJNR: May 1982 edition.

PMID- 28507221
TI  - Allocation of antiretroviral drugs to HIV-infected patients in Togo: perspectives
      of people living with HIV and healthcare providers.
AB  - AIM: To explore the way people living with HIV and healthcare providers in Togo
      judge the priority of HIV-infected patients regarding the allocation of
      antiretroviral drugs. METHOD: From June to September 2015, 200 adults living with
      HIV and 121 healthcare providers living in Togo were recruited for the study.
      They were presented with stories of a few lines depicting the situation of an HIV
      infected patient and were instructed to judge the extent to which the patient
      should be given priority for antiretroviral drugs. The stories were composed by
      systematically varying the levels of four factors: (a) the severity of HIV
      infection, (b) the financial situation of the patient, (c) the patient's family
      responsibilities and (d) the time elapsed since the first consultation. RESULTS:
      Five clusters were identified: 65% of the participants expressed the view that
      patients who are poor and severely sick should be treated as a priority, 13%
      prioritised treatment of patients who are poor and parents of small children, 12%
      expressed the view that the poor should be treated as a priority, 4% preferred
      that the sickest be treated as a priority and 6% wanted all patients to get
      treatment. CONCLUSIONS: WHO's guideline regarding antiretroviral therapy
      allocation (the sickest first as the sole criterion) currently in use in many
      African countries does not reflect the preferences of Togolese people living with
      HIV. For most HIV-infected patients in Togo, patients who cannot get treatment on
      their own should be treated as a priority.

PMID- 28507219
TI  - Subcutaneous golimumab for children with active polyarticular-course juvenile
      idiopathic arthritis: results of a multicentre, double-blind, randomised
      withdrawal trial.
AB  - OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and
      efficacy of subcutaneous golimumab in active polyarticular-course juvenile
      idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double
      blinded placebo-controlled withdrawal trial, all patients received open-label
      golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks
      together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at
      least 30% improvement per American College of Rheumatology Criteria for JIA (JIA
      ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1
      randomisation to continue golimumab or start placebo. In Part 3, golimumab was
      continued or could be restarted as in Part 1. The primary outcome was JIA flares
      in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical
      remission, PK and safety. RESULTS: Among 173 patients with polyJIA enrolled,
      89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA
      ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as
      treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41%
      vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab
      vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event
      rates were similar in the treatment groups during Part 2. Injection site
      reactions occurred with <1% of all injections. PK analysis confirmed adequate
      golimumab dosing for polyJIA. CONCLUSION: Although the primary endpoint was not
      met, golimumab resulted in rapid, clinically meaningful, improvement in children
      with active polyJIA. Golimumab was well tolerated, and no unexpected safety
      events occurred. CLINICAL TRIAL REGISTRATION: NCT01230827; Results.

PMID- 28507222
TI  - Meeting the goal of concurrent adolescent and adult licensure of HIV prevention
      and treatment strategies.
AB  - The ability of adolescents to access safe and effective new products for HIV
      prevention and treatment is optimised by adolescent licensure at the same time
      these products are approved and marketed for adults. Many adolescent product
      development programmes for HIV prevention or treatment products may proceed
      simultaneously with adult phase III development programmes. Appropriately
      implemented, this strategy is not expected to delay licensure as information
      regarding product efficacy can often be extrapolated from adults to adolescents,
      and pharmacokinetic properties of drugs in adolescents are expected to be similar
      to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention
      and treatment research can be considered adults, based on US Food and Drug
      Administration (FDA) regulations and the appropriate application of state law.
      The FDA permits local jurisdictions to apply state and local HIV/sexually
      transmitted infection minor treatment laws so that adolescents who are HIV
      positive or at risk of contracting HIV may be enrolled in therapeutic or
      prevention trials without obtaining parental permission.

PMID- 28507223
TI  - Should neurotechnological treatments offered to offenders always be in their best
      interests?
AB  - The paper critically discusses the moral view that neurotechnological behavioural
      treatment for criminal offenders should only be offered if it is in their best
      interests. First, I show that it is difficult to apply and assess the notion of
      the offender's best interests unless one has a clear idea of what 'best
      interests' means. Second, I argue that if one accepts that harmful punishment of
      offenders has a place in the criminal justice system, it seems inconsistent not
      to accept the practice of offering offenders treatment even when the state will
      harm them in applying the treatment. Finally, leading penal theories like
      consequentialists and retributivists would not accept that the offender's best
      interests, at least in certain situations, impose a necessary condition for the
      treatment of an offender.

PMID- 28507224
TI  - c-MYC mRNA tail tale about glutamine control of transcription.

PMID- 28507226
TI  - Peripheral retinopathy associated with Waldenstrom's macroglobulinaemia.

PMID- 28507227
TI  - When two wrongs make a right: synchronized neuronal bursting from combined
      electrical and inhibitory coupling.
AB  - Synchronized cortical activities in the central nervous systems of mammals are
      crucial for sensory perception, coordination and locomotory function. The
      neuronal mechanisms that generate synchronous synaptic inputs in the neocortex
      are far from being fully understood. In this paper, we study the emergence of
      synchronization in networks of bursting neurons as a highly non-trivial, combined
      effect of electrical and inhibitory connections. We report a counterintuitive
      find that combined electrical and inhibitory coupling can synergistically induce
      robust synchronization in a range of parameters where electrical coupling alone
      promotes anti-phase spiking and inhibition induces anti-phase bursting. We reveal
      the underlying mechanism, which uses a balance between hidden properties of
      electrical and inhibitory coupling to act together to synchronize neuronal
      bursting. We show that this balance is controlled by the duty cycle of the self
      coupled system which governs the synchronized bursting rhythm.This article is
      part of the themed issue 'Mathematical methods in medicine: neuroscience,
      cardiology and pathology'.

PMID- 28507225
TI  - Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin
      tumorigenesis.
AB  - Tissue homeostasis of skin is sustained by epidermal progenitor cells localized
      within the basal layer of the skin epithelium. Post-translational modification of
      the proteome, such as protein phosphorylation, plays a fundamental role in the
      regulation of stemness and differentiation of somatic stem cells. However, it
      remains unclear how phosphoproteomic changes occur and contribute to epidermal
      differentiation. In this study, we survey the epidermal cell differentiation in a
      systematic manner by combining quantitative phosphoproteomics with mammalian
      kinome cDNA library screen. This approach identified a key signaling event,
      phosphorylation of a desmosome component, PKP1 (plakophilin-1) by RIPK4 (receptor
      interacting serine-threonine kinase 4) during epidermal differentiation. With
      genome-editing and mouse genetics approach, we show that loss of function of
      either Pkp1 or Ripk4 impairs skin differentiation and enhances epidermal
      carcinogenesis in vivo Phosphorylation of PKP1's N-terminal domain by RIPK4 is
      essential for their role in epidermal differentiation. Taken together, our study
      presents a global view of phosphoproteomic changes that occur during epidermal
      differentiation, and identifies RIPK-PKP1 signaling as novel axis involved in
      skin stratification and tumorigenesis.

PMID- 28507228
TI  - Understanding principles of integration and segregation using whole-brain
      computational connectomics: implications for neuropsychiatric disorders.
AB  - To survive in an ever-changing environment, the brain must seamlessly integrate a
      rich stream of incoming information into coherent internal representations that
      can then be used to efficiently plan for action. The brain must, however, balance
      its ability to integrate information from various sources with a complementary
      capacity to segregate information into modules which perform specialized
      computations in local circuits. Importantly, evidence suggests that imbalances in
      the brain's ability to bind together and/or segregate information over both space
      and time is a common feature of several neuropsychiatric disorders. Most studies
      have, however, until recently strictly attempted to characterize the principles
      of integration and segregation in static (i.e. time-invariant) representations of
      human brain networks, hence disregarding the complex spatio-temporal nature of
      these processes. In the present Review, we describe how the emerging discipline
      of whole-brain computational connectomics may be used to study the causal
      mechanisms of the integration and segregation of information on behaviourally
      relevant timescales. We emphasize how novel methods from network science and
      whole-brain computational modelling can expand beyond traditional neuroimaging
      paradigms and help to uncover the neurobiological determinants of the abnormal
      integration and segregation of information in neuropsychiatric disorders.This
      article is part of the themed issue 'Mathematical methods in medicine:
      neuroscience, cardiology and pathology'.

PMID- 28507229
TI  - Spread of competing viruses on heterogeneous networks.
AB  - In this paper, we propose a model where two strains compete with each other at
      the expense of common susceptible individuals on heterogeneous networks by using
      pair-wise approximation closed by the probability-generating function (PGF). All
      of the strains obey the susceptible-infected-recovered (SIR) mechanism. From a
      special perspective, we first study the dynamical behaviour of an SIR model
      closed by the PGF, and obtain the basic reproduction number via two methods. Then
      we build a model to study the spreading dynamics of competing viruses and discuss
      the conditions for the local stability of equilibria, which is different from the
      condition obtained by using the heterogeneous mean-field approach. Finally, we
      perform numerical simulations on Barabasi-Albert networks to complement our
      theoretical research, and show some dynamical properties of the model with
      competing viruses.This article is part of the themed issue 'Mathematical methods
      in medicine: neuroscience, cardiology and pathology'.

PMID- 28507231
TI  - Biological modelling of a computational spiking neural network with neuronal
      avalanches.
AB  - In recent years, an increasing number of studies have demonstrated that networks
      in the brain can self-organize into a critical state where dynamics exhibit a
      mixture of ordered and disordered patterns. This critical branching phenomenon is
      termed neuronal avalanches. It has been hypothesized that the homeostatic level
      balanced between stability and plasticity of this critical state may be the
      optimal state for performing diverse neural computational tasks. However, the
      critical region for high performance is narrow and sensitive for spiking neural
      networks (SNNs). In this paper, we investigated the role of the critical state in
      neural computations based on liquid-state machines, a biologically plausible
      computational neural network model for real-time computing. The computational
      performance of an SNN when operating at the critical state and, in particular,
      with spike-timing-dependent plasticity for updating synaptic weights is
      investigated. The network is found to show the best computational performance
      when it is subjected to critical dynamic states. Moreover, the active-neuron
      dominant structure refined from synaptic learning can remarkably enhance the
      robustness of the critical state and further improve computational accuracy.
      These results may have important implications in the modelling of spiking neural
      networks with optimal computational performance.This article is part of the
      themed issue 'Mathematical methods in medicine: neuroscience, cardiology and
      pathology'.

PMID- 28507230
TI  - Computational design of treatment strategies for proactive therapy on atopic
      dermatitis using optimal control theory.
AB  - Atopic dermatitis (AD) is a common chronic skin disease characterized by
      recurrent skin inflammation and a weak skin barrier, and is known to be a
      precursor to other allergic diseases such as asthma. AD affects up to 25% of
      children worldwide and the incidence continues to rise. There is still
      uncertainty about the optimal treatment strategy in terms of choice of treatment,
      potency, duration and frequency. This study aims to develop a computational
      method to design optimal treatment strategies for the clinically recommended
      'proactive therapy' for AD. Proactive therapy aims to prevent recurrent flares
      once the disease has been brought under initial control. Typically, this is done
      by using an anti-inflammatory treatment such as a potent topical corticosteroid
      intensively for a few weeks to 'get control', followed by intermittent weekly
      treatment to suppress subclinical inflammation to 'keep control'. Using a hybrid
      mathematical model of AD pathogenesis that we recently proposed, we
      computationally derived the optimal treatment strategies for individual virtual
      patient cohorts, by recursively solving optimal control problems using a
      differential evolution algorithm. Our simulation results suggest that such an
      approach can inform the design of optimal individualized treatment schedules that
      include application of topical corticosteroids and emollients, based on the
      disease status of patients observed on their weekly hospital visits. We
      demonstrate the potential and the gaps of our approach to be applied to clinical
      settings.This article is part of the themed issue 'Mathematical methods in
      medicine: neuroscience, cardiology and pathology'.

PMID- 28507232
TI  - Energy landscape analysis of neuroimaging data.
AB  - Computational neuroscience models have been used for understanding neural
      dynamics in the brain and how they may be altered when physiological or other
      conditions change. We review and develop a data-driven approach to neuroimaging
      data called the energy landscape analysis. The methods are rooted in statistical
      physics theory, in particular the Ising model, also known as the (pairwise)
      maximum entropy model and Boltzmann machine. The methods have been applied to
      fitting electrophysiological data in neuroscience for a decade, but their use in
      neuroimaging data is still in its infancy. We first review the methods and
      discuss some algorithms and technical aspects. Then, we apply the methods to
      functional magnetic resonance imaging data recorded from healthy individuals to
      inspect the relationship between the accuracy of fitting, the size of the brain
      system to be analysed and the data length.This article is part of the themed
      issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

PMID- 28507234
TI  - Modelling far field pacing for terminating spiral waves pinned to ischaemic
      heterogeneities in cardiac tissue.
AB  - In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be
      unpinned (and eventually terminated) using electric far field pulses and
      recruiting the heterogeneity as a virtual electrode. While for isotropic media
      the process of unpinning is much better understood, the case of an anisotropic
      substrate with different conductivities in different directions still needs
      intensive investigation. To study the impact of anisotropy on the unpinning
      process, we present numerical simulations based on the bidomain formulation of
      the phase I of the Luo and Rudy action potential model modified due to the
      occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave
      pinned to an ischaemic heterogeneity, we compare the success of sequences of far
      field pulses in the isotropic and the anisotropic case for spirals still in
      transient or in steady rotation states. Our results clearly indicate that the
      range of pacing parameters resulting in successful termination of pinned spiral
      waves is larger in anisotropic tissue than in an isotropic medium.This article is
      part of the themed issue 'Mathematical methods in medicine: neuroscience,
      cardiology and pathology'.

PMID- 28507233
TI  - Transient sequences in a hypernetwork generated by an adaptive network of spiking
      neurons.
AB  - We propose a model of an adaptive network of spiking neurons that gives rise to a
      hypernetwork of its dynamic states at the upper level of description. Left to
      itself, the network exhibits a sequence of transient clustering which relates to
      a traffic in the hypernetwork in the form of a random walk. Receiving inputs the
      system is able to generate reproducible sequences corresponding to stimulus
      specific paths in the hypernetwork. We illustrate these basic notions by a simple
      network of discrete-time spiking neurons together with its FPGA realization and
      analyse their properties.This article is part of the themed issue 'Mathematical
      methods in medicine: neuroscience, cardiology and pathology'.

PMID- 28507235
TI  - Assessing the strength of cardiac and sympathetic baroreflex controls via
      transfer entropy during orthostatic challenge.
AB  - The study assesses the strength of the causal relation along baroreflex (BR) in
      humans during an incremental postural challenge soliciting the BR. Both cardiac
      BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches
      from spontaneous fluctuations of heart period (HP), systolic arterial pressure
      (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity
      (MSNA). A model-based transfer entropy method was applied to quantify the
      strength of the coupling from SAP to HP and from DAP to MSNA. The confounding
      influences of respiration were accounted for. Twelve young healthy subjects (20
      36 years, nine females) were sequentially tilted at 0 degrees , 20 degrees , 30
      degrees  and 40 degrees . We found that (i) the strength of the causal relation
      along the cBR increases with tilt table inclination, while that along the sBR is
      unrelated to it; (ii) the strength of the causal coupling is unrelated to the
      gain of the relation; (iii) transfer entropy indexes are significantly and
      positively associated with simplified causality indexes derived from BR sequence
      analysis. The study proves that causality indexes are complementary to
      traditional characterization of the BR and suggests that simple markers derived
      from BR sequence analysis might be fruitfully exploited to estimate causality
      along the BR.This article is part of the themed issue 'Mathematical methods in
      medicine: neuroscience, cardiology and pathology'.

PMID- 28507236
TI  - Dynamics of the cell-mediated immune response to tumour growth.
AB  - Using a hybrid cellular automaton, we investigate the transient and asymptotic
      dynamics of the cell-mediated immune response to tumour growth. We analyse the
      correspondence between this dynamics and the three phases of the theory of
      immunoedition: elimination, equilibrium and escape. Our results demonstrate that
      the immune system can keep a tumour dormant for long periods of time, but that
      this dormancy is based on a frail equilibrium between the mechanisms that spur
      the immune response and the growth of the tumour. Thus, we question the capacity
      of the cell-mediated immune response to sustain long periods of dormancy, as
      those appearing in recurrent disease. We suggest that its role might be rather to
      synergize with other types of tumour dormancy.This article is part of the themed
      issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

PMID- 28507237
TI  - Multiscale ordinal network analysis of human cardiac dynamics.
AB  - In this study, we propose a new information theoretic measure to quantify the
      complexity of biological systems based on time-series data. We demonstrate the
      potential of our method using two distinct applications to human cardiac
      dynamics. Firstly, we show that the method clearly discriminates between segments
      of electrocardiogram records characterized by normal sinus rhythm, ventricular
      tachycardia and ventricular fibrillation. Secondly, we investigate the multiscale
      complexity of cardiac dynamics with respect to age in healthy individuals using
      interbeat interval time series and compare our findings with a previous study
      which established a link between age and fractal-like long-range correlations.
      The method we use is an extension of the symbolic mapping procedure originally
      proposed for permutation entropy. We build a Markov chain of the dynamics based
      on order patterns in the time series which we call an ordinal network, and from
      this model compute an intuitive entropic measure of transitional complexity. A
      discussion of the model parameter space in terms of traditional time delay
      embedding provides a theoretical basis for our multiscale approach. As an
      ancillary discussion, we address the practical issue of node aliasing and how
      this effects ordinal network models of continuous systems from discrete time
      sampled data, such as interbeat interval time series.This article is part of the
      themed issue 'Mathematical methods in medicine: neuroscience, cardiology and
      pathology'.

PMID- 28507238
TI  - Clustering: how much bias do we need?
AB  - Scientific investigations in medicine and beyond increasingly require
      observations to be described by more features than can be simultaneously
      visualized. Simply reducing the dimensionality by projections destroys essential
      relationships in the data. Similarly, traditional clustering algorithms introduce
      data bias that prevents detection of natural structures expected from generic
      nonlinear processes. We examine how these problems can best be addressed, where
      in particular we focus on two recent clustering approaches, Phenograph and
      Hebbian learning clustering, applied to synthetic and natural data examples. Our
      results reveal that already for very basic questions, minimizing clustering bias
      is essential, but that results can benefit further from biased post
      processing.This article is part of the themed issue 'Mathematical methods in
      medicine: neuroscience, cardiology and pathology'.

PMID- 28507239
TI  - Pulsatile flow in ventricular catheters for hydrocephalus.
AB  - The obstruction of ventricular catheters (VCs) is a major problem in the standard
      treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF)
      being one important factor thereof. As a first approach to this problem, some of
      the authors studied previously the CSF flow through VCs under time-independent
      boundary conditions by means of computational fluid dynamics in three-dimensional
      models. This allowed us to derive a few basic principles which led to designs
      with improved flow patterns regarding the obstruction problem. However, the flow
      of the CSF has actually a pulsatile nature because of the heart beating and blood
      flow. To address this fact, here we extend our previous computational study to
      models with oscillatory boundary conditions. The new results will be compared
      with the results for constant flows and discussed. It turns out that the
      corrections due to the pulsatility of the CSF are quantitatively small, which
      reinforces our previous findings and conclusions.This article is part of the
      themed issue 'Mathematical methods in medicine: neuroscience, cardiology and
      pathology'.

PMID- 28507240
TI  - Mathematical methods in medicine: neuroscience, cardiology and pathology.
AB  - The application of mathematics, natural sciences and engineering to medicine is
      gaining momentum as the mutual benefits of this collaboration become increasingly
      obvious. This theme issue is intended to highlight the trend in the case of
      mathematics. Specifically, the scope of this theme issue is to give a general
      view of the current research in the application of mathematical methods to
      medicine, as well as to show how mathematics can help in such important aspects
      as understanding, prediction, treatment and data processing. To this end, three
      representative specialties have been selected: neuroscience, cardiology and
      pathology. Concerning the topics, the 12 research papers and one review included
      in this issue cover biofluids, cardiac and virus dynamics, computational
      neuroscience, functional magnetic resonance imaging data processing, neural
      networks, optimization of treatment strategies, time-series analysis and tumour
      growth. In conclusion, this theme issue contains a collection of fine
      contributions at the intersection of mathematics and medicine, not as an exercise
      in applied mathematics but as a multidisciplinary research effort that interests
      both communities and our society in general.This article is part of the themed
      issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

PMID- 28507242
TI  - An RpoHI-Dependent Response Promotes Outgrowth after Extended Stationary Phase in
      the Alphaproteobacterium Rhodobacter sphaeroides.
AB  - Under unfavorable growth conditions, bacteria enter stationary phase and can
      maintain cell viability over prolonged periods with no increase in cell number.
      To obtain insights into the regulatory mechanisms that allow bacteria to resume
      growth when conditions become favorable again (outgrowth), we performed global
      transcriptome analyses at different stages of growth for the alphaproteobacterium
      Rhodobacter sphaeroides The majority of genes were not differentially expressed
      across growth phases. After a short stationary phase (about 20 h after growth
      starts to slow down), only 7% of the genes showed altered expression (fold change
      of >1.6 or less than -1.6, corresponding to a log2 fold change of >0.65 or less
      than -0.65, respectively) compared to expression at exponential phase. Outgrowth
      induced a distinct response in gene expression which was strongly influenced by
      the length of the preceding stationary phase. After a long stationary phase
      (about 64 h after growth starts to slow down), a much larger number of genes
      (15.1%) was induced in outgrowth than after a short stationary phase (1.7%). Many
      of those genes are known members of the RpoHI/RpoHII regulons and have
      established functions in stress responses. A main effect of RpoHI on the
      transcriptome in outgrowth after a long stationary phase was confirmed. Growth
      experiments with mutant strains further support an important function in
      outgrowth after prolonged stationary phase for the RpoHI and RpoHII sigma
      factors.IMPORTANCE In natural environments, the growth of bacteria is limited
      mostly by lack of nutrients or other unfavorable conditions. It is important for
      bacterial populations to efficiently resume growth after being in stationary
      phase, which may last for long periods. Most previous studies on growth-phase
      dependent gene expression did not address outgrowth after stationary phase. This
      study on growth-phase-dependent gene regulation in a model alphaproteobacterium
      reveals, for the first time, that the length of the stationary phase strongly
      impacts the transcriptome during outgrowth. The alternative sigma factors RpoHI
      and RpoHII, which are important regulators of stress responses in
      alphaproteobacteria, play a major role during outgrowth following prolonged
      stationary phase. These findings provide the first insight into the regulatory
      mechanisms enabling efficient outgrowth.

PMID- 28507241
TI  - An Amino Acid Substitution in RNA Polymerase That Inhibits the Utilization of an
      Alternative Sigma Factor.
AB  - Sigma (sigma) factors direct gene transcription by binding to and determining the
      promoter recognition specificity of RNA polymerase (RNAP) in bacteria. Genes
      transcribed under the control of alternative sigma factors allow cells to respond
      to stress and undergo developmental processes, such as sporulation in Bacillus
      subtilis, in which gene expression is controlled by a cascade of alternative
      sigma factors. Binding of sigma factors to RNA polymerase depends on the coiled
      coil (or clamp helices) motif of the beta' subunit. We have identified an amino
      acid substitution (L257P) in the coiled coil that markedly inhibits the function
      of sigmaH, the earliest-acting alternative sigma factor in the sporulation
      cascade. Cells with this mutant RNAP exhibited an early and severe block in
      sporulation but not in growth. The mutant was strongly impaired in sigmaH
      directed gene expression but not in the activity of the stress-response sigma
      factor sigmaB Pulldown experiments showed that the mutant RNAP was defective in
      associating with sigmaH but could still associate with sigmaA and sigmaB The
      differential effects of the L257P substitution on sigma factor binding to RNAP
      are likely due to a conformational change in the beta' coiled coil that is
      specifically detrimental for interaction with sigmaH This is the first example,
      to our knowledge, of an amino acid substitution in RNAP that exhibits a strong
      differential effect on a particular alternative sigma factor.IMPORTANCE In
      bacteria, all transcription is mediated by a single multisubunit RNA polymerase
      (RNAP) enzyme. However, promoter-specific transcription initiation necessitates
      that RNAP associates with a sigma factor. Bacteria contain a primary sigma factor
      that directs transcription of housekeeping genes and alternative sigma factors
      that direct transcription in response to environmental or developmental cues. We
      identified an amino acid substitution (L257P) in the B. subtilis beta' subunit
      whereby RNAPL257P associates with some sigma factors (sigmaA and sigmaB) and
      enables vegetative cell growth but is defective in utilization of sigmaH and is
      consequently blocked for sporulation. To our knowledge, this is the first
      identification of an amino acid substitution within the core enzyme that affects
      utilization of a specific sigma factor.

PMID- 28507243
TI  - Modular Organization of the NusA- and NusG-Stimulated RNA Polymerase Pause Signal
      That Participates in the Bacillus subtilis trp Operon Attenuation Mechanism.
AB  - The Bacillus subtilis trpEDCFBA operon is regulated by a transcription
      attenuation mechanism in which tryptophan-activated TRAP binds to the nascent
      transcript and blocks the formation of an antiterminator structure such that the
      formation of an overlapping intrinsic terminator causes termination in the 5'
      untranslated region (5' UTR). In the absence of bound TRAP, the antiterminator
      forms and transcription continues into the trp genes. RNA polymerase pauses at
      positions U107 and U144 in the 5' UTR. The general transcription elongation
      factors NusA and NusG stimulate pausing at both positions. NusG-stimulated
      pausing at U144 requires sequence-specific contacts with a T tract in the
      nontemplate DNA (ntDNA) strand within the paused transcription bubble. Pausing at
      U144 participates in a trpE translation repression mechanism. Since U107 just
      precedes the critical overlap between the antiterminator and terminator
      structures, pausing at this position is thought to participate in attenuation.
      Here we carried out in vitro pausing and termination experiments to identify
      components of the U107 pause signal and to determine whether pausing affects the
      termination efficiency in the 5' UTR. We determined that the U107 and U144 pause
      signals are organized in a modular fashion containing distinct RNA hairpin, U
      tract, and T-tract components. NusA-stimulated pausing was affected by hairpin
      strength and the U-tract sequence, whereas NusG-stimulated pausing was affected
      by hairpin strength and the T-tract sequence. We also determined that pausing at
      U107 results in increased TRAP-dependent termination in the 5' UTR, implying that
      NusA- and NusG-stimulated pausing participates in the trp operon attenuation
      mechanism by providing additional time for TRAP binding.IMPORTANCE The expression
      of several bacterial operons is controlled by regulated termination in the 5'
      untranslated region (5' UTR). Transcription attenuation is defined as situations
      in which the binding of a regulatory molecule promotes transcription termination
      in the 5' UTR, with the default being transcription readthrough into the
      downstream genes. RNA polymerase pausing is thought to participate in several
      attenuation mechanisms by synchronizing the position of RNA polymerase with RNA
      folding and/or regulatory factor binding, although this has only been shown in a
      few instances. We found that NusA- and NusG-stimulated pausing participates in
      the attenuation mechanism controlling the expression of the Bacillus subtilis trp
      operon by increasing the TRAP-dependent termination efficiency. The pause signal
      is organized in a modular fashion containing RNA hairpin, U-tract, and T-tract
      components.

PMID- 28507247
TI  - The Long and Winding Road After FDA Approval: A Medical Device Industry
      Perspective.

PMID- 28507244
TI  - Inhibition of Staphylococcus aureus Cell Wall Biosynthesis by Desleucyl
      Oritavancin: a Quantitative Peptidoglycan Composition Analysis by Mass
      Spectrometry.
AB  - Oritavancin is a lipoglycopeptide antibiotic that exhibits potent activities
      against vancomycin-resistant Gram-positive pathogens. Oritavancin differs from
      vancomycin by a hydrophobic side chain attached to the drug disaccharide, which
      forms a secondary binding site to enable oritavancin binding to the cross-linked
      peptidoglycan in the cell wall. The mode of action of secondary binding site was
      investigated by measuring the changes in the peptidoglycan composition of
      Staphylococcus aureus grown in the presence of desleucyl-oritavancin at
      subinhibitory concentration using liquid chromatography-mass spectrometry (LC
      MS). Desleucyl-oritavancin is an Edman degradation product of oritavancin that
      exhibits potent antibacterial activities despite the damaged d-Ala-d-Ala binding
      site due to its functional secondary binding site. Accurate quantitative
      peptidoglycan composition analysis based on 83 muropeptide ions determined that
      cell walls of S. aureus grown in the presence of desleucyl-oritavancin showed a
      reduction of peptidoglycan cross-linking, increased muropeptides with a
      tetrapeptide-stem structure, decreased O-acetylation of MurNAc, and increased N
      deacetylation of GlcNAc. The changes in peptidoglycan composition suggest that
      desleucyl-oritavancin targets the peptidoglycan template to induce cell wall
      disorder and interferes with cell wall maturation.IMPORTANCE Oritavancin is a
      lipoglycopeptide antibiotic with a secondary binding site that targets the cross
      linked peptidoglycan bridge structure in the cell wall. Even after the loss of
      its primary d-Ala-d-Ala binding site through Edman degradation, desleucyl
      oritavancin exhibits potent antimicrobial activities through its still
      functioning secondary binding site. In this study, we characterized the mode of
      action for desleucyl-oritavancin's secondary binding site using LC-MS.
      Peptidoglycan composition analysis of desleucyl-oritavancin-treated S. aureus was
      performed by determining the relative abundances of 83 muropeptide ions matched
      from a precalculated library through integrating extracted ion chromatograms. Our
      work highlights the use of quantitative peptidoglycan composition analysis by LC
      MS to provide insights into the mode of action of glycopeptide antibiotics.

PMID- 28507245
TI  - Conformational Changes of an Interdomain Linker Mediate Mechanical Signal
      Transmission in Sensor Kinase BvgS.
AB  - The whooping cough agent, Bordetella pertussis, controls the expression of its
      large virulence regulon in a coordinated manner through the two-component system
      BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in
      succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane
      segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional
      phosphorelay domains. BvgS shifts between kinase and phosphatase modes of
      activity in response to chemical modulators that modify the clamshell motions of
      the VFT domains. We have shown previously that this regulation involves a shift
      between distinct states of conformation and dynamics of the two-helix coiled-coil
      linker preceding the enzymatic module. In this work, we determined the mechanism
      of signal transduction across the membrane via a first linker, which connects the
      VFT and PAS domains of BvgS, using extensive cysteine cross-linking analyses and
      other approaches. Modulator perception by the periplasmic domains appears to
      trigger a small, symmetrical motion of the transmembrane segments toward the
      periplasm, causing rearrangements of the noncanonical cytoplasmic coiled coil
      that follows. As a consequence, the interface of the PAS domains is modified,
      which affects the second linker and eventually causes the shift of enzymatic
      activity. The major features of this first linker are well conserved among BvgS
      homologs, indicating that the mechanism of signal transduction unveiled here is
      likely to be generally relevant for this family of sensor
      kinases.IMPORTANCEBordetella pertussis produces virulence factors coordinately
      regulated by the two-component system BvgAS. BvgS is a sensor kinase, and BvgA is
      a response regulator that activates gene transcription when phosphorylated by
      BvgS. Sensor kinases homologous to BvgS are also found in other pathogens. Our
      goal is to decipher the mechanisms of BvgS signaling, since these sensor kinases
      may represent new targets for antibacterial agents. Signal perception by the
      sensor domains of BvgS triggers small motions of the helical linker region
      underneath. The protein domain that follows this linker undergoes a large
      conformational change that amplifies the initial signal, causing a shift of
      activity from kinase to phosphatase. Because BvgS homologs harbor similar
      regions, these signaling mechanisms are likely to apply generally to that family
      of sensor kinases.

PMID- 28507248
TI  - New Hope For People With Dysglycemia and Cardiovascular Disease Manifestations:
      Reduction of Acute Coronary Events With Pioglitazone.

PMID- 28507249
TI  - Response to Outlier Status: Lessons From Public Reporting for Percutaneous
      Coronary Intervention.

PMID- 28507246
TI  - The Pneumococcal Type 1 Pilus Genes Are Thermoregulated and Are Repressed by a
      Member of the Snf2 Protein Family.
AB  - In Streptococcus pneumoniae, the type 1 pilus is involved in many steps of
      pathogenesis, including adherence to epithelial cells, mediation of inflammation,
      escape from macrophages, and the formation of biofilms. The type 1 pilus genes
      are expressed in a bistable fashion with cells switching between "on" and "off"
      expression states. Bistable expression of these genes is due to their control by
      RlrA, a positive regulator subject to control by a positive-feedback loop. The
      type 1 pilus genes are also thought to be negatively regulated by a large number
      of repressors. Here we show that expression of the type 1 pilus genes is
      thermosensitive and switched off at growth temperatures below 31 degrees C. We
      also report that the on expression state of the type 1 pilus genes is highly
      stable, a phenomenon which we show likely contributed to the erroneous
      identification of many proteins as negative regulators of these genes. Finally,
      we exploited the effect of low temperature on pilus gene expression to help
      identify SP_1523, an Snf2-type protein, as a novel negative regulator of the
      pilus genes. Our findings establish that the type 1 pilus genes are
      thermoregulated and are repressed by a member of the Snf2 protein family. They
      also refute the notion that these genes are controlled by 8 previously described
      negative regulators.IMPORTANCEStreptococcus pneumoniae is the leading cause of
      death from respiratory infections in children. Many bacterial factors contribute
      to pneumococcal virulence and nasopharyngeal colonization. The type 1
      pneumococcal pilus plays an important role in mouse models and in epithelial
      adherence and is expressed in a bistable fashion. Here we show that the "on"
      state is highly stable, which may explain the prior misidentification of negative
      regulators of pilus expression. We also show that expression of pilus genes is
      thermosensitive: virtually no expression can be detected at temperatures found in
      the anterior nares of humans. We took advantage of this property to identify a
      negative regulator of pilus expression, a member of a family of proteins widely
      conserved across Gram-positive bacteria.

PMID- 28507250
TI  - A Rock and a Hard Place: Chiseling Away at the Multiple Mechanisms of Aortic
      Stenosis.

PMID- 28507251
TI  - Stress Testing in Asymptomatic Aortic Stenosis.
AB  - Aortic stenosis is 1 of the most common heart valve diseases among adults. When
      symptoms develop, prognosis is poor, and current guidelines recommend prompt
      aortic valve replacement. Depending of the severity of the aortic stenosis and
      the presence of concomitant heart disease and medical comorbidities, stress
      testing represents a reasonable strategy to help better risk stratify
      asymptomatic patients. The present report provides a comprehensive review of the
      current available data on stress testing in aortic stenosis and subsequently
      summarizes its potential for guiding the optimal timing of aortic valve
      replacement.

PMID- 28507252
TI  - Winter Is Coming After a Cardiac Arrest.

PMID- 28507253
TI  - Primary Stable Microvascular Angina: A Long-Term Clinical Follow-Up Study.

PMID- 28507254
TI  - Letter by Ma et al Regarding Article, "Neuroprotective Effects of the Glucagon
      Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A
      Randomized Controlled Trial".

PMID- 28507255
TI  - Response by Wiberg et al to Letter Regarding Article, "Neuroprotective Effects of
      the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac
      Arrest: A Randomized Controlled Trial".

PMID- 28507256
TI  - Letter by Tuncez et al Regarding Article, "Identifying Patients at Risk for
      Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction:
      The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies Therapeutiques
      des infarctus du myocarde)".

PMID- 28507258
TI  - Letter by Rottenberg Regarding Article, "Conventional Versus Compression-Only
      Versus No Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital
      Cardiac Arrest".

PMID- 28507257
TI  - Response by Karam et al to Letter Regarding Article, "Identifying Patients at
      Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial
      Infarction: The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies
      Therapeutiques des infarctus du myocarde)".

PMID- 28507259
TI  - Spotlight on the May 16 issue.

PMID- 28507262
TI  - Editors' Note.

PMID- 28507260
TI  - Reprogramming cells from Gulf War veterans into neurons to study Gulf War
      illness.
AB  - Gulf War illness (GWI), which afflicts at least 25% of veterans who served in the
      1990-1991 war in the Persian Gulf, is thought to be caused by deployment
      exposures to various neurotoxicants, including pesticides, anti-nerve gas pills,
      and low-level nerve agents including sarin/cyclosarin. GWI is a multisymptom
      disorder characterized by fatigue, joint pain, cognitive problems, and
      gastrointestinal complaints. The most prominent symptoms of GWI (memory problems,
      poor attention/concentration, chronic headaches, mood alterations, and impaired
      sleep) suggest that the disease primarily affects the CNS. Development of
      urgently needed treatments depends on experimental models appropriate for testing
      mechanistic hypotheses and for screening therapeutic compounds. Rodent models
      have been useful thus far, but are limited by their inability to assess the
      contribution of genetic or epigenetic background to the disease, and because
      disease-vulnerable proteins and pathways may be different in humans relative to
      rodents. As of yet, no postmortem tissue from the veterans has become available
      for research. We are moving forward with a paradigm shift in the study of GWI,
      which utilizes contemporary stem cell technology to convert somatic cells from
      Gulf War veterans into pluripotent cell lines that can be differentiated into
      various cell types, including neurons, glia, muscle, or other relevant cell
      types. Such cell lines are immortal and will be a resource for GWI researchers to
      pursue mechanistic hypotheses and therapeutics.

PMID- 28507261
TI  - Pure sensory ganglionopathy as the first sign of relapse in non-Hodgkin lymphoma.

PMID- 28507264
TI  - Author response: Mystery Case: CSF-1R mutation is a cause of intracranial
      cerebral calcifications, cysts, and leukoencephalopathy.

PMID- 28507263
TI  - Letter re: Mystery Case: CSF-1R mutation is a cause of intracranial cerebral
      calcifications, cysts, and leukoencephalopathy.

PMID- 28507266
TI  - Mystery Case: CSF-1R mutation is a cause of intracranial cerebral calcifications,
      cysts, and leukoencephalopathy.

PMID- 28507265
TI  - Summary author response: Mystery Case: CSF-1R mutation is a cause of intracranial
      cerebral calcifications, cysts, and leukoencephalopathy.

PMID- 28507267
TI  - Teaching NeuroImages: Takayasu arteritis: Neuroimaging progression after
      immunosuppressant treatment.

PMID- 28507268
TI  - Teaching NeuroImages: Prominent spinal cord atrophy and white matter changes in
      adult polyglucosan body disease.

PMID- 28507271
TI  - Correction: Integration of Novel Agents into the Care of Patients with Multiple
      Myeloma.

PMID- 28507269
TI  - Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue
      Plasminogen Activator for Acute Stroke).
AB  - BACKGROUND AND PURPOSE: We conducted a randomized exploratory study to assess
      safety and the probability of a favorable outcome with adjunctive argatroban, a
      direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen
      activator (r-tPA)-treated ischemic stroke patients. METHODS: Patients treated
      with standard-dose r-tPA, not receiving endovascular therapy, were randomized to
      receive no argatroban or argatroban (100 MUg/kg bolus) followed by infusion of
      either 1 (low dose) or 3 MUg/kg per minute (high dose) for 48 hours. Safety was
      incidence of symptomatic intracerebral hemorrhage. Probability of clinical
      benefit (modified Rankin Scale score 0-1 at 90 days) was estimated using a
      conservative Bayesian Poisson model (neutral prior probability centered at
      relative risk, 1.0 and 95% prior intervals, 0.33-3.0). RESULTS: Ninety patients
      were randomized: 29 to r-tPA alone, 30 to r-tPA+low-dose argatroban, and 31 to r
      tPA+high-dose argatroban. Rates of symptomatic intracerebral hemorrhage were
      similar among control, low-dose, and high-dose arms: 3/29 (10%), 4/30 (13%), and
      2/31 (7%), respectively. At 90 days, 6 (21%) r-tPA alone, 9 (30%) low-dose, and
      10 (32%) high-dose patients were with modified Rankin Scale score 0 to 1. The
      relative risks (95% credible interval) for modified Rankin Scale score 0 to 1
      with low, high, and either low or high dose argatroban were 1.17 (0.57-2.37),
      1.27 (0.63-2.53), and 1.34 (0.68-2.76), respectively. The probability that
      adjunctive argatroban was superior to r-tPA alone was 67%, 74%, and 79% for low,
      high, and low or high dose, respectively. CONCLUSIONS: In patients treated with r
      tPA, adjunctive argatroban was not associated with increased risk of symptomatic
      intracerebral hemorrhage and provides evidence that a definitive effectiveness
      trial is indicated. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique Identifier: NCT01464788.

PMID- 28507274
TI  - Targeted next generation sequencing identifies somatic mutations and gene fusions
      in papillary thyroid carcinoma.
AB  - 138 papillary thyroid carcinoma (PTC) samples were assessed for somatic mutation
      profile and fusion genes by targeted resequencing using a cancer panel
      (ThyGenCapTM) targeting 244 cancer-related genes and 20 potential fusion genes.
      At least one genetic alteration (including mutations and fusion genes) was
      observed in 118/138 (85.5%) samples. The most frequently mutated gene was BRAF
      V600E (57.2%). Moreover, we identified 11 fusion genes including eight previously
      reported ones and three novel fusion genes, UEVLD-RET, OSBPL9-BRAF, and SQSTM1
      NTRK3. Alterations affecting the mitogen-activated protein kinase (MAPK)
      signaling pathway components were seen in 69.6% of the PTC cases and all of these
      driver mutations were mutually exclusive. Univariate analysis ascertained that
      the fusion genes were strongly associated with distinct clinicopathological
      characteristics, such as young age, local invasion, extensive metastasis, and
      disease stage. In conclusion, our approach facilitated simultaneous high
      throughput detection of gene fusions and somatic mutations in PTC samples.

PMID- 28507272
TI  - Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics
      during clathrin-mediated endocytosis.
AB  - Endocytic turnover is essential for the regulation of the protein composition and
      function of the plasma membrane, and thus affects the plasma membrane levels of
      many receptors. In Drosophila melanogaster photoreceptors, photon absorption by
      the G-protein-coupled receptor (GPCR) rhodopsin 1 (Rh1; also known as NinaE)
      triggers its endocytosis through clathrin-mediated endocytosis (CME). We find
      that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase
      (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded
      endomembranes within the cell body. This mislocalization of Rh1 was dependent on
      the formation of an expanded Rab5-positive compartment. The Rh1-trafficking
      defect in PIP4K-depleted cells could be suppressed by downregulating Rab5
      function or by selectively reconstituting PIP4K in the PI3P-enriched early
      endosomal compartment of photoreceptors. We also found that loss of PIP4K was
      associated with increased CME and an enlarged Rab5-positive compartment in
      cultured Drosophila cells. Collectively, our findings define PIP4K as a novel
      regulator of early endosomal homeostasis during CME.

PMID- 28507275
TI  - Quantitative proteomics profiling reveals activation of mTOR pathway in
      trastuzumab resistance.
AB  - Trastuzumab is an antibody-based therapy drug targeting HER2-overexpressing
      tumors. While it has been proven to be very successful initially, most patients
      eventually develop resistance to trastuzumab. The mechanism of drug resistance is
      not well understood. Identifying pathways that mediate trastuzumab resistance
      will improve our understanding of the underlying mechanism and is crucial for the
      development of therapeutic strategies to overcome resistance.Here we report a
      quantitative proteomics profiling of a trastuzumab-sensitive (T-S) gastric cancer
      cell line NCI N87 and a trastuzumab-resistant NCI N87 (T-R) subline generated by
      low-dose, continuous trastuzumab treatment. By identifying proteins
      differentially expressed in these two cell lines, we show that multiple pathways
      including mTOR, Wnt, DNA damage response and metabolic pathways are significantly
      altered. We further confirm by western blotting that protein levels of multiple
      components of the mTOR pathway, including mTOR, AKT and RPS6KB1, are increased,
      whereas AKT1S1 is decreased, suggesting the activation of mTOR pathway.
      Importantly, treatment of AZD8055, an mTOR inhibitor, leads to the decreased
      phosphorylation levels of mTOR downstream molecules RPS6KB1 at Thr421/Ser424 and
      AKT at Ser473. Furthermore, AZD8055 also preferentially reduces viability, and
      inhibits migration and invasion abilities of the T-R cells. Together, our
      findings indicate that mTOR pathway is among multiple signaling pathways that
      mediate trastuzumab resistance in NCI N87 T-R cells, and that mTOR inhibitors may
      be used to treat trastuzumab resistant, HER2-positive gastric cancer tumors.

PMID- 28507277
TI  - Notch1 regulates the JNK signaling pathway and increases apoptosis in
      hepatocellular carcinoma.
AB  - Notch1-induced pathways are involved in cell growth, apoptosis, motility, and
      invasion in many cancers. In the present study, the expression of Notch1 and
      NICD1 was detected in hepatocellular carcinoma (HCC) tissues using in-vitro
      assays. And then, we explored cell biology and signaling pathways using Notch1
      siRNA or plasmids. Here, the expression of Notch1 and NICD1 was significantly
      decreased in HCC tissues. In-vitro, Notch1 plasmids inhibited cell proliferation,
      migration and invasion, but enhanced apoptosis of HepG2 and Hep3B cells.
      Conversely, si-Notch1 enhanced cell proliferation, migration and invasion, but
      inhibited apoptosis of HepG2 and Hep3B cells. Mechanically, Notch1 decreased the
      expression of cyclin D1, MMP-9 and Bcl-2, but increased the expression of p-JNK,
      Bax and cleaved caspase 3 in HepG2 and Hep3B cells. Besides, si-JNK or JNK
      inhibitor SP600125 affected the activation of Notch1 signaling pathway, and
      prevents cell apoptosis. In conclusion, Notch1 regulates the JNK signaling
      pathway and increases apoptosis in HCC. Because patients with HCC have a poor
      prognosis, Notch1 pathway may provide a novel treatment strategy.

PMID- 28507278
TI  - Regulation of CD44v6 expression in gastric carcinoma by the IL-6/STAT3 signaling
      pathway and its clinical significance.
AB  - As a cancer stem cell marker, CD44 variant 6 (CD44v6) has been implicated in
      carcinogenesis, tumor progression, and metastasis in a variety of human
      carcinomas. However, little is known about the expression of CD44v6 in Gastric
      Carcinoma (GC). Therefore we investigated CD44v6 expression in clinical specimen
      and further explore the underlying molecular mechanisms.In this study, we
      systemically investigated CD44v6 expression by immunohistochemistry in normal,
      premalignant gastric mucosa (low and high grade intraepithelial neoplasia), and
      GC at various stages. The correlation of CD44v6 expression with
      clinicopathological characteristics, and prognosis in GC was also analyzed. Next,
      we investigated cell proliferation, migration and invasion in GC cell lines.
      Furthermore, we explored a novel mechanism by which CD44V6 was upregulated in GC
      cell.The immunohistochemistry results showed that enhanced expression of CD44v6
      was closely associated with tumor differentiation, lymph node metastasis, TNM
      stage and poor prognosis in GC patients. In gastric cancer cell lines, CD44v6
      involved in cell proliferation, invasion and metastasis in Next, report on a
      novel mechanism by which interleukin-6/signal transducer and activator of
      transcription 3 (IL-6/STAT3) signaling up-regulates expression of CD44v6. RNA
      interference silencing of STAT3 resulted in decrease of CD44v6 levels. We also
      found that STAT3 inhibitor AG490 decrease expression of CD44v6 by blocking
      activation of STAT3, even in the presence of IL-6. Targeting STAT3-mediated
      CD44v6 up-regulation may represent a novel, effective treatment by eradicating
      the stomach tumor microenvironment.

PMID- 28507279
TI  - Prognostic significance of soluble mesothelin in malignant pleural mesothelioma:
      a meta-analysis.
AB  - BACKGROUND: Soluble mesothelin is beneficial to detect the progression and the
      treatment response of malignant pleural mesothelioma. However, the prognostic
      value of soluble mesothelin in malignant pleural mesothelioma remains unclear.
      METHODS: Hazard ratio with 95% CI was used to evaluate the prognostic value of
      soluble mesothelin and the effect of clinicopathological characteristics on the
      survival of malignant pleural mesothelioma. RESULTS: Eight eligible studies
      involving 579 patients were selected for this meta-analysis. The results showed
      that soluble mesothelin level was significantly correlated with the survival of
      malignant pleural mesothelioma (pooled HR: 1.958, 95%CI: 1.531-2.504, p = 0.000;
      heterogeneity test: I2 = 1.1%, p = 0.421). In addition, the survival of malignant
      pleural mesothelioma was significantly correlated with some clinicopathological
      characteristics such as tumor histology (HR = 3.214, 95% CI = 2.071-4.988, p =
      0.000; heterogeneity test: I2 = 0.0%, p = 0.623) and tumor stage (HR = 2.007; 95%
      CI = 1.477-2.727; p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.966).
      CONCLUSIONS: The survival of malignant pleural mesothelioma is significantly
      correlated with tumor histology and tumor stage. Furthermore, high soluble
      mesothelin level may lead to a poor prognosis for malignant pleural mesothelioma
      patients.

PMID- 28507281
TI  - High expression of long non-coding RNA NEAT1 indicates poor prognosis of human
      cancer.
AB  - The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA.
      Many studies have reported that NEAT1 plays critical oncogenic roles and
      facilitates tumorigenesis of various human cancers. High NEAT1 expression is
      associated with a poor prognosis in cancer patients. This meta-analysis was
      conducted to assess the association between NEAT1 levels and survival times of
      cancer patients. Overall survival (OS) was the primary endpoint. Thirteen
      publications with 1,496 cancer patients from 5 databases (PubMed, EMBASE,
      Cochrane Library, Wiley Online Library, and Medline) met the criteria for this
      meta-analysis. Results of the analysis showed that NEAT1 expression in human
      cancer was significantly associated with OS (hazard ratio [HR]=1.53, 95%
      confidence interval [CI]: 1.39-1.68), including digestive system tumor (HR=1.54,
      95% CI: 1.37-1.73) and respiratory carcinomas (HR=1.44, 95% CI: 1.11-1.85). The
      results also indicated that NEAT1 expression was highly associated with tumor
      size (>3 cm vs. <=3 cm; odds ratio [OR]=2.51, 95% CI: 1.27-4.99; p=0.009), TNM
      stage (III+IV vs. I+II; OR=4.17, 95% CI: 2.42-7.18; p=0.00001), and distant
      metastasis (OR=2.73, 95% CI: 1.28-5.79; p=0.01). However, there was no
      significant association with differentiation (poor vs. well + moderate, OR=1.45,
      95% CI: 0.72-2.91) and lymph node metastasis (OR=1.39, 95% CI: 0.54-3.60). This
      meta-analysis showed that NEAT1 expression may be a useful biomarker for
      predicting a poor prognosis in patients with cancer.

PMID- 28507280
TI  - Molecular dissection of effector mechanisms of RAS-mediated resistance to anti
      EGFR antibody therapy.
AB  - Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR),
      cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC)
      treatment. However, a significant number of patients suffer from primary or
      acquired resistance. RAS mutations are negative predictors of clinical efficacy
      of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK
      and PI3K/AKT pathways, which are considered the main effectors of resistance.
      However, the relative impact of these pathways in RAS-mutant CRC is less defined.
      A better mechanistic understanding of RAS-mediated resistance may guide
      development of rational intervention strategies. To this end we developed cancer
      models for functional dissection of resistance to anti-EGFR therapy in vitro and
      in vivo. To selectively activate MAPK- or AKT-signaling we expressed
      conditionally activatable RAF-1 and AKT in cancer cells. We found that either
      pathway independently protected sensitive cancer models against anti-EGFR
      antibody treatment in vitro and in vivo. RAF-1- and AKT-mediated resistance was
      associated with increased expression of anti-apoptotic BCL-2 proteins. Biomarkers
      of MAPK and PI3K/AKT pathway activation correlated with inferior outcome in a
      cohort of mCRC patients receiving cetuximab-based therapy. Dual pharmacologic
      inhibition of PI3K and MEK successfully sensitized primary resistant CRC models
      to anti-EGFR therapy. In conclusion, combined targeting of MAPK and PI3K/AKT
      signaling, but not single pathways, may be required to enhance the efficacy of
      anti-EGFR antibody therapy in patients with RAS-mutated CRC as well as in RAS
      wild type tumors with clinical resistance.

PMID- 28507283
TI  - MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its
      Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by
      Targeting Methylene Tetrahydrofolate Reductase (MTHFR).
AB  - BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a worldwide health
      problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The
      objective of our study was to explore the effect of polymorphism in miR-149 on
      the pathogenesis of NAFLD. MATERIAL AND METHODS Real-time PCR was performed to
      explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and
      methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and
      luciferase assay were investigated to verify MTHFR was the target gene of miR
      149. Finally, Western-blot analysis and real-time PCR were performed to confirm
      the control of MTHFR by miR-149. RESULTS In this study, we found that miR-149 was
      apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR
      in hepatocytes genotyped as TT treated with FFA was evidently downregulated
      compared to control. Whereas, FFA had no obvious effect on MTHFR level in
      hepatocytes genotyped as CC. We searched an online miRNA database and found that
      miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase
      assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149
      mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose
      dependently increased the level of MTHFR. And in hepatocytes genotyped as CC
      treated with or without FFA exhibited a similar inhibition effect of miR-149 on
      expression of MTHFR. CONCLUSIONS The data suggested that the polymorphism in miR
      149 played an important role in the development of NAFLD via altering the
      expression of miR-149 as well as its target, MTHFR.

PMID- 28507282
TI  - P53 suppresses ribonucleotide reductase via inhibiting mTORC1.
AB  - Balanced deoxyribonucleotides pools are essential for cell survival and genome
      stability. Ribonucleotide reductase is the rate-limiting enzyme for the
      production of deoxyribonucleotides. We report here that p53 suppresses
      ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian
      target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse
      embryonic fibroblast cells were treated with different concentrations of
      pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30
      cell tumor-bearing mice were treated with rapamycin or AZD8055. Protein levels
      and phosphorylation status were assessed by immunoblotting and mRNA levels were
      determined by real time RT-PCR. Pharmacological inhibition of mTORC1 with
      rapamycin, mTOR kinase with AZD8055 or protein kinase B with MK2206 resulted in
      decrease of RRM1 and RRM2 in Rh30 cells both in vitro and in mouse tumor
      xenografts. Moreover, eukaryotic translational initiation factor 4E-binding
      proteins 1 and 2 double knockout mouse embryonic fibroblast cells demonstrated an
      elevation of RRM1 and RRM2. Furthermore, down-regulation of mTOR-protein kinase B
      signaling or cyclin dependent kinase 4 led to decrease of RRM1 and RRM2 mRNAs. In
      addition, TP53 mutant cancer cells had elevation of RRM1 and RRM2, which was
      reduced by rapamycin. Importantly, human double minute 2 inhibitor nutlin-3
      decreased RRM1 and RRM2 in TP53 wild type rhabdomyosarcoma Rh18 but not in TP53
      mutated Rh30 cells. Our data demonstrated that mTOR enhances the cap-dependent
      protein translation and gene transcription of RRM1 and RRM2. Our findings might
      provide an additional mechanism by which p53 maintains genome stability.

PMID- 28507284
TI  - Melanoma Masquerading as a Zosteriform Rash.
AB  - BACKGROUND Primary care physicians and internal medicine specialists frequently
      encounter a variety of rashes. Many of these cases look and feel typical of
      common entities, resulting in the potential for misdiagnosis. CASE REPORT This is
      a case of a zosteriform rash where the surprising true diagnosis of metastatic
      melanoma was confirmed with bedside skin punch biopsy. Possible mechanisms
      involve direct cutaneous injury, neuronal, and dorsal root ganglia involvement in
      metastases. CONCLUSIONS Skin biopsy is indispensable especially when there is a
      lack of clinical response or deterioration in the clinical condition. The
      pathophysiology of zosteriform metastasis is unclear.

PMID- 28507285
TI  - Multivariate EEG analyses support high-resolution tracking of feature-based
      attentional selection.
AB  - The primary electrophysiological marker of feature-based selection is the N2pc, a
      lateralized posterior negativity emerging around 180-200 ms. As it relies on
      hemispheric differences, its ability to discriminate the locus of focal attention
      is severely limited. Here we demonstrate that multivariate analyses of raw EEG
      data provide a much more fine-grained spatial profile of feature-based target
      selection. When training a pattern classifier to determine target position from
      EEG, we were able to decode target positions on the vertical midline, which
      cannot be achieved using standard N2pc methodology. Next, we used a forward
      encoding model to construct a channel tuning function that describes the
      continuous relationship between target position and multivariate EEG in an eight
      position display. This model can spatially discriminate individual target
      positions in these displays and is fully invertible, enabling us to construct
      hypothetical topographic activation maps for target positions that were never
      used. When tested against the real pattern of neural activity obtained from a
      different group of subjects, the constructed maps from the forward model turned
      out statistically indistinguishable, thus providing independent validation of our
      model. Our findings demonstrate the power of multivariate EEG analysis to track
      feature-based target selection with high spatial and temporal precision.

PMID- 28507286
TI  - Complexes of DNA with fluorescent dyes are effective reagents for detection of
      autoimmune antibodies.
AB  - To date, there are multiple assays developed that detect and quantify antibodies
      in biofluids. Nevertheless, there is still a lack of simple approaches that
      specifically detect autoimmune antibodies to double-stranded DNA. Herein we
      investigate the potential of novel nucleic acid complexes as targets for these
      antibodies. This is done in a simple, rapid and specific immunofluorescence
      assay. Specifically, employing 3D nanostructures (DNA origami), we present a new
      approach in the detection and study of human antibodies to DNA. We demonstrate
      the detection of anti-DNA antibodies that are characteristic of systemic lupus
      erythematosus, a chronic autoimmune disease with multiple manifestations. We
      tested the most potent non-covalent pairs of DNA and fluorescent dyes. Several
      complexes showed specific recognition of autoimmune antibodies in human samples
      of lupus patients using a simple one-step immunofluorescence method. This makes
      the novel assay developed herein a promising tool for research and point-of-care
      monitoring of anti-DNA antibodies. Using this method, we for the first time
      experimentally confirm that the disease-specific autoimmune antibodies are
      sensitive to the 3D structure of nucleic acids and not only to the nucleotide
      sequence, as was previously thought.

PMID- 28507287
TI  - Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of
      endometrial epithelial cell receptivity for blastocyst implantation.
AB  - Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst
      first interacts with the luminal endometrial epithelial cells during its
      implantation; therefore, we have investigated the signaling of ITGB8 via FAK and
      VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated
      in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5,
      0500 h) stages of endometrial receptivity period in the mouse. Integrins
      downstream molecule FAK has demonstrated an increased expression and
      phosphorylation (Y397) in the endometrium as well as in the isolated endometrial
      epithelial cells during receptive and post-receptive stages. Integrin beta8 can
      functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK,
      and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the
      endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly
      active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK
      for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of
      ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered
      poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1
      signaling axis via FAK to facilitate the endometrial epithelial cell receptivity
      for the attachment of blastocyst.

PMID- 28507288
TI  - Identifying individuals with physician-diagnosed chronic obstructive pulmonary
      disease in primary care electronic medical records: a retrospective chart
      abstraction study.
AB  - : Little is known about using electronic medical records to identify patients
      with chronic obstructive pulmonary disease to improve quality of care. Our
      objective was to develop electronic medical record algorithms that can accurately
      identify patients with obstructive pulmonary disease. A retrospective chart
      abstraction study was conducted on data from the Electronic Medical Record
      Administrative data Linked Database (EMRALD(r)) housed at the Institute for
      Clinical Evaluative Sciences. Abstracted charts provided the reference standard
      based on available physician-diagnoses, chronic obstructive pulmonary disease
      specific medications, smoking history and pulmonary function testing. Chronic
      obstructive pulmonary disease electronic medical record algorithms using
      combinations of terminology in the cumulative patient profile (CPP; problem
      list/past medical history), physician billing codes (chronic
      bronchitis/emphysema/other chronic obstructive pulmonary disease), and
      prescriptions, were tested against the reference standard. Sensitivity,
      specificity, and positive/negative predictive values (PPV/NPV) were calculated.
      There were 364 patients with chronic obstructive pulmonary disease identified in
      a 5889 randomly sampled cohort aged >= 35 years (prevalence = 6.2%). The
      electronic medical record algorithm consisting of >= 3 physician billing codes
      for chronic obstructive pulmonary disease per year; documentation in the CPP;
      tiotropium prescription; or ipratropium (or its formulations) prescription and a
      chronic obstructive pulmonary disease billing code had sensitivity of 76.9% (95%
      CI:72.2-81.2), specificity of 99.7% (99.5-99.8), PPV of 93.6% (90.3-96.1), and
      NPV of 98.5% (98.1-98.8). Electronic medical record algorithms can accurately
      identify patients with chronic obstructive pulmonary disease in primary care
      records. They can be used to enable further studies in practice patterns and
      chronic obstructive pulmonary disease management in primary care. CHRONIC LUNG
      DISEASE: NOVEL ALGORITHM SEARCH TECHNIQUE: Researchers develop an algorithm that
      can accurately search through electronic health records to find patients with
      chronic lung disease. Mining population-wide data for information on patients
      diagnosed and treated with chronic obstructive pulmonary disease (COPD) in
      primary care could help inform future healthcare and spending practices. Theresa
      Lee at the University of Toronto, Canada, and colleagues used an algorithm to
      search electronic medical records and identify patients with COPD from doctors'
      notes, prescriptions and symptom histories. They carefully adjusted the algorithm
      to improve sensitivity and predictive value by adding details such as specific
      medications, physician codes related to COPD, and different combinations of
      terminology in doctors' notes. The team accurately identified 364 patients with
      COPD in a randomly-selected cohort of 5889 people. Their results suggest
      opportunities for broader, informative studies of COPD in wider populations.

PMID- 28507289
TI  - Cells reprogramming to stem cells inhibit the reprogramming of adjacent cells in
      the moss Physcomitrella patens.
AB  - Under certain circumstances differentiated cells can be reprogrammed to form stem
      cells in land plants, but only a portion of the cells reprograms successfully. A
      long-distance inhibitory signal from reprogrammed cells to surrounding cells has
      been reported in some ferns. Here we show the existence of anisotropic inhibitory
      signal to regulate stem cell formation in the moss Physcomitrella patens. When
      single cells were isolated from a gametophore leaf, over 90% of them were
      reprogrammed to stem cells with characteristic nuclear expansion. By contrast,
      when two adjacent cells were isolated, the nuclei of both cells expanded, but
      successful reprogramming of both cells occurred only in approximately one fifth
      of the pairs. When three aligned cells were isolated, the reprogramming rate of
      both edge cells decreased with a living middle cell but did not with a dead
      middle cell. Furthermore, unequal conversion into stem cells was more prominent
      in cell pairs aligned parallel to the proximal-distal leaf axis than in those
      perpendicular to the axis. This study gives an insight into the role of the
      inhibitory signal in development and evolution as well as the efficient stem cell
      induction from differentiated cells.

PMID- 28507290
TI  - Effects of the non-parabolic kinetic energy on non-equilibrium polariton
      condensates.
AB  - In the study of non-equilibrium polariton condensates it is usually assumed that
      the dispersion relation of polaritons is parabolic in nature. We show that
      considering the true non-parabolic kinetic energy of polaritons leads to
      significant changes in the behaviour of the condensate due to the curvature of
      the dispersion relation and the possibility of transfer of energy to high
      wavenumber components in the condensate spatial profile. We present explicit
      solutions for plane waves and linear excitations, and identify the differences in
      the theoretical predictions between the parabolic and non-parabolic mean-field
      models, showing the possibility of symmetry breaking in the latter. We then
      consider the evolution of wavepackets and show that self-localisation effects may
      be observed due to the curvature of the dispersion relation. Finally, we revisit
      the dynamics of dark soliton trains and show that additional localized density
      excitations may emerge in the dynamics due to the excitation of high frequency
      components, mimicking the appearance of near-bright solitary waves over short
      timescales.

PMID- 28507291
TI  - Construction of genotyping-by-sequencing based high-density genetic maps and QTL
      mapping for fusarium wilt resistance in pigeonpea.
AB  - Fusarium wilt (FW) is one of the most important biotic stresses causing yield
      losses in pigeonpea. Genetic improvement of pigeonpea through genomics-assisted
      breeding (GAB) is an economically feasible option for the development of high
      yielding FW resistant genotypes. In this context, two recombinant inbred lines
      (RILs) (ICPB 2049 * ICPL 99050 designated as PRIL_A and ICPL 20096 * ICPL 332
      designated as PRIL_B) and one F2 (ICPL 85063 * ICPL 87119) populations were used
      for the development of high density genetic maps. Genotyping-by-sequencing (GBS)
      approach was used to identify and genotype SNPs in three mapping populations. As
      a result, three high density genetic maps with 964, 1101 and 557 SNPs with an
      average marker distance of 1.16, 0.84 and 2.60 cM were developed in PRIL_A,
      PRIL_B and F2, respectively. Based on the multi-location and multi-year
      phenotypic data of FW resistance a total of 14 quantitative trait loci (QTLs)
      including six major QTLs explaining >10% phenotypic variance explained (PVE) were
      identified. Comparative analysis across the populations has revealed three
      important QTLs (qFW11.1, qFW11.2 and qFW11.3) with upto 56.45% PVE for FW
      resistance. This is the first report of QTL mapping for FW resistance in
      pigeonpea and identified genomic region could be utilized in GAB.

PMID- 28507292
TI  - Growth, Properties, and Theoretical Analysis of M2LiVO4 (M = Rb, Cs) Crystals:
      Two Potential Mid-Infrared Nonlinear Optical Materials.
AB  - Mid-Infrared nonlinear optical (Mid-IR NLO) crystals with excellent performances
      play a particularly important role for applications in areas such as
      telecommunications, laser guidance, and explosives detection. However, the design
      and growth of high performance Mid-IR NLO crystals with large NLO efficiency and
      high laser-damage threshold (LDT) still face numerous fundamental challenge. In
      this study, two potential Mid-IR NLO materials, Rb2LiVO4 (RLVO) and Cs2LiVO4
      (CLVO) with noncentrosymmetric structures (Orthorhombic, Cmc21) were synthesized
      by high-temperature solution method. Thermal analysis and powder X-ray
      diffraction demonstrate that RLVO and CLVO melt congruently. Centimeter sized
      crystals of CLVO have been grown by the top-seeded solution growth method. RLVO
      and CLVO exhibit strong second harmonic generation (SHG) effects (about 4 and 5
      times that of KH2PO4, respectively) with a phase-matching behavior at 1.064 MUm,
      and a wide transparency range (0.33-6.0 MUm for CLVO). More importantly, RLVO and
      CLVO possess a high LDT value (~28 * AgGaS2). In addition, the density functional
      theory (DFT) and dipole moments studies indicate that the VO4 anionic groups have
      a dominant contribution to the SHG effects in RLVO and CLVO. These results
      suggest that the title compounds are promising NLO candidate crystals applied in
      the Mid-IR region.

PMID- 28507293
TI  - Exploring optoelectronic properties and mechanisms of layered ferroelectric
      K4Nb6O17 nanocrystalline films and nanolaminas.
AB  - Two-dimensional layered K4Nb6O17 (KN) was easily formed as a secondary phase
      caused by the volatilization of alkali metal ions, when preparing ferroelectric K
      x Na1-x NbO3 based ceramics and films. In this work, it was believed that KN film
      is with weak ferroelectricity and has a little effect on the ferroelectric
      properties of K x Na1-x NbO3 based films. Moreover, temperature dependent (77-500
      K) dielectric functions of KN film have been firstly extracted by fitting
      ellipsometric spectra with the Adachi dielectric function model and a four-phase
      layered model. The high-frequency dielectric constant linearly increases and
      optical band gap slightly decreases with increasing the temperature. We also
      research its photoelectrochemical properties and its application in high
      efficient light-induced H2 evolution. In addition, X-ray photoelectron
      spectroscopy, Raman scattering, temperature dependent transmittance and infrared
      reflectance spectra, and first-principles calculation were conjointly performed
      to further reveal the intrinsic optoelectronic features and relevant mechanisms
      of KN.

PMID- 28507295
TI  - Self-assembled levitating clusters of water droplets: pattern-formation and
      stability.
AB  - Water forms ordered hexagonally symmetric structures (snow crystals) in its solid
      state, however not as liquid. Typically, mists and clouds are composed of
      randomly moving small droplets lacking any ordered structure. Self-organized
      hexagonally patterned microdroplet clusters over locally heated water surfaces
      have been recently observed. However, many aspects of the phenomenon are far from
      being well understood including what determines droplets size, arrangement, and
      the distance between them. Here we show that the Voronoi entropy of the cluster
      tends to decrease indicating to their self-organization, while coupling of
      thermal effects and mechanical forces controls the stability of the clusters. We
      explain the balance of the long-range attraction and repulsion forces which
      stabilizes the cluster patterns and established the range of parameters, for
      which the clusters are stable. The cluster is a dissipative structure similar to
      self-organized Rayleigh-Benard convective cells. Microdroplet formation plays a
      role in a variety effects from mist and clouds to aerosols. We anticipate that
      the discovery of the droplet cluster phenomenon and its explanation will provide
      new insights on the fundamental physical and chemical processes such as
      microdroplet role in reaction catalysis in nature as well as new tools for
      aerosol analysis and microfluidic applications.

PMID- 28507294
TI  - Laparoscopic versus opengastric surgery for the treatment of pathological T1N0M0
      gastric cancer in elderly patients: a matched study.
AB  - The aim of this study was to compare the outcomes of laparoscopic surgery (LAP)
      and open gastric surgery (OP) in early gastric cancer patients aged >=70 years.We
      conducted a retrospectively analysis among patientswith pathological T1N0M0
      gastric cancer,who underwent LAP or OP between January 1, 2001 and December 31,
      2008. We identified a well-balanced cohort of 2,360 patients (1180 patients in
      each group). LAP has been shown to offer a superior perioperative results to OP,
      including lower blood loss, shorter time to oral intake, walk and bowel function
      recovery, shorter time of hospital stay, and less blood transfusion required.
      However, the intraoperative and postoperative complications, local recurrence,
      and metastasis didn't show statistically significant differences between groups.
      The 5-year overall survival (OS), disease-free survival (DFS), and cancer
      specific survival (CSS) were 60.1% vs.63.2%, 80.8% vs. 83.3%, and 87.6% vs. 89.5%
      in the LAP group and OP group, respectively. The hazard ratios (HR) for OS, DFS,
      and CSS were 1.09(95% confidence interval [CI]: 0.95-1.25; P = 0.215), 1.03(95%
      CI: 0.91-1.18; P = 0.636), and 1.07 (95% CI: 0.88-1.30; P = 0.484), respectively,
      compared LAP group with OP group. In conclusion, LAP is an acceptable alternative
      to OP in elderly patients with early gastric cancer.

PMID- 28507296
TI  - Sleep disorder, an independent risk associated with arterial stiffness in
      menopause.
AB  - As women age and go through menopause, they suffer a higher incidence of sleep
      disorder, cardiovascular morbidity and mortality. In addition, evidences
      suggested that sleep disorder was an important pathological indicator for
      coronary heart disease. However, the relationship between different menopausal
      status, sleep disorder and cardiovascular diseases was unclear. Thus, we aim to
      assess the association between sleep disorder with arterial stiffness in females
      of 40-60 years free of cardiovascular diseases through self-administered
      Pittsburgh Sleep Quality Index (PSQI) and brachial-ankle pulse wave velocity
      (baPWV). Logistic regression revealed that sleep disorder (PSQI score >= 8) was
      an independent indicator for higher risk of elevated arterial stiffness (baPWV >=
      1465.5 cm/s, upper tertile) beyond other established cardiovascular confounders
      in peri-postmenopause (OR 2.83, 95% confidence interval (CI) 2.00-4.00, p <
      0.001), but not in premenopause (OR 1.67, 95% CI 0.71-3.90, p = 0.223).
      Collectively, it clearly indicates that sleep disorder in menopausal women is of
      prominent value to predict arterial stiffness.

PMID- 28507297
TI  - A One-Pot Three-Component Double-Click Method for Synthesis of [67Cu]-Labeled
      Biomolecular Radiotherapeutics.
AB  - A one-pot three-component double-click process for preparing tumor-targeting
      agents for cancer radiotherapy is described here. By utilizing DOTA (or NOTA)
      containing tetrazines and the TCO-substituted aldehyde, the two click reactions,
      the tetrazine ligation (an inverse electron-demand Diels-Alder cycloaddition) and
      the RIKEN click (a rapid 6pi-azaelectrocyclization), could simultaneously proceed
      under mild conditions to afford covalent attachment of the metal chelator DOTA or
      NOTA to biomolecules such as to albumin and anti-IGSF4 antibody without altering
      their activities. Subsequently, radiolabeling of DOTA- or NOTA-attached albumin
      and anti-IGSF4 antibody (an anti-tumor-targeting antibody) with [67Cu], a beta-
      emitting radionuclide, could be achieved in a highly efficient manner via a
      simple chelation with DOTA proving to be a more superior chelator than NOTA. Our
      work provides a new and operationally simple method for introducing the [67Cu]
      isotope even in large quantities to biomolecules, thereby representing an
      important process for preparations of clinically relevant tumor-targeting agents
      for radiotherapy.

PMID- 28507301
TI  - Erratum: Molecular characterization reveals the complexity of previously
      overlooked coral-exosymbiont interactions and the implications for coral-guild
      ecology.

PMID- 28507298
TI  - Protective effects of APOE e2 against disease progression in subcortical vascular
      mild cognitive impairment patients: A three-year longitudinal study.
AB  - Although the association between apolipoprotein E (APOE) genotype and disease
      progression is well characterized in patients with Alzheimer's disease, such a
      relationship is unknown in patients with subcortical vascular cognitive
      impairment. We evaluated whether APOE genotype is associated with disease
      progression in subcortical vascular mild cognitive impairment (svMCI) patients.
      We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3
      homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with
      brain MRI and neuropsychological tests for three years and underwent a second
      Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-beta
      burden was quantified by PiB standardized uptake value ratio (SUVR), and the
      amount of small vessel disease was quantified by number of lacune and small
      vessel disease score on MRI. We also measured cortical thickness. During the
      three years of follow-up, compared to the APOE3 homozygotes, there was less
      increase in PiB SUVR among APOE2 carriers (p = 0.023), while the APOE genotype
      did not show significant effects on small vessel disease progression. APOE2
      carriers also showed less cortical thinning (p = 0.023) and a slower rate of
      cognitive decline (p = 0.009) compared to those with APOE3 homozygotes. Our
      findings suggest that, in svMCI patients, APOE2 has protective effects against
      amyloid-beta accumulation, cortical thinning, and cognitive decline.

PMID- 28507299
TI  - The Fatty Acid beta-Oxidation Pathway is Activated by Leucine Deprivation in
      HepG2 Cells: A Comparative Proteomics Study.
AB  - Leucine (Leu) is a multifunctional essential amino acid that plays crucial role
      in various cellular processes. However, the integral effect of Leu on the hepatic
      proteome remains largely unknown. Here, we for the first time applied an isobaric
      tags for relative and absolute quantification (iTRAQ)-based comparative
      proteomics strategy to investigate the proteome alteration induced by Leu
      deprivation in human hepatocellular carcinoma (HepG2) cells. A total of 4,111
      proteins were quantified; 43 proteins were further identified as differentially
      expressed proteins between the normal and Leu deprivation groups. Bioinformatics
      analysis showed that the differentially expressed proteins were involved in
      various metabolic processes, including amino acid and lipid metabolism, as well
      as degradation of ethanol. Interestingly, several proteins involved in the fatty
      acid beta-oxidation pathway, including ACSL1, ACADS, and ACOX1, were up-regulated
      by Leu deprivation. In addition, Leu deprivation led to the reduction of cellular
      triglycerides in HepG2 cells. These results reveal that the fatty acid beta
      oxidation pathway is activated by Leu deprivation in HepG2 cells, and provide new
      insights into the regulatory function of Leu in multiple cellular processes,
      especially fatty acid metabolism.

PMID- 28507302
TI  - Impedance self-matching ultra-narrow linewidth fiber resonator by use of a
      tunable pi-phase-shifted FBG.
AB  - In this paper, we present a novel ultra-narrow linewidth fiber resonator formed
      by a tunable polarization maintaining (PM) pi-phase-shifted fiber Bragg grating
      and a PM uniform fiber Bragg grating with a certain length of PM single mode
      fiber patch cable between them. Theoretical prediction shows that this resonator
      has ultra-narrow linewidth resonant peaks and is easy to realize impedance
      matching. We experimentally obtain 3 MHz narrow linewidth impedance matched
      resonant peak in a 7.3 m ultra-long passive fiber cavity. The impedance self
      matching characteristic of this resonator also makes itself particularly suitable
      for use in ultra-sensitive sensors, ultra-narrow band rejection optical filters
      and fiber lasers applications.

PMID- 28507300
TI  - Minimum toe clearance: probing the neural control of locomotion.
AB  - Minimum toe clearance (MTC) occurs during a highly dynamic phase of the gait
      cycle and is associated with the highest risk of unintentional contact with
      obstacles or the ground. Age, cognitive function, attention and visual feedback
      affect foot clearance but how these factors interact to influence MTC control is
      not fully understood. We measured MTC in 121 healthy individuals aged 20-80 under
      four treadmill walking conditions; normal walking, lower visual field restriction
      and two Stroop colour/word naming tasks of two difficulty levels. Competition for
      cognitive and attentional resources from the Stroop task resulted in
      significantly lower mean MTC in older adults, with the difficult Stroop task
      associated with a higher frequency of extremely low MTC values and subsequently
      an increased modelled probability of tripping in this group. While older adults
      responded to visual restriction by markedly skewing MTC distributions towards
      higher values, this condition was also associated with frequent, extremely low
      MTC values. We reveal task-specific, age-dependent patterns of MTC control in
      healthy adults. Age-related differences are most pronounced during heavy,
      distracting cognitive load. Analysis of critically-low MTC values during dual
      task walking may have utility in the evaluation of locomotor control and fall
      risk in older adults and patients with motor control deficits.

PMID- 28507303
TI  - Silver Nanoparticles-Decorated Titanium Oxynitride Nanotube Arrays for Enhanced
      Solar Fuel Generation.
AB  - We demonstrate, for the first time, the synthesis of highly ordered titanium
      oxynitride nanotube arrays sensitized with Ag nanoparticles (Ag/TiON) as an
      attractive class of materials for visible-light-driven water splitting. The
      nanostructure topology of TiO2, TiON and Ag/TiON was investigated using FESEM and
      TEM. The X-ray photoelectron spectroscopy (XPS) and the energy dispersive X-ray
      spectroscopy (EDS) analyses confirm the formation of the oxynitride structure.
      Upon their use to split water photoelectrochemically under AM 1.5 G illumination
      (100 mW/cm2, 0.1 M KOH), the titanium oxynitride nanotube array films showed
      significant increase in the photocurrent (6 mA/cm2) compared to the TiO2
      nanotubes counterpart (0.15 mA/cm2). Moreover, decorating the TiON nanotubes with
      Ag nanoparticles (13 +/- 2 nm in size) resulted in exceptionally high
      photocurrent reaching 14 mA/cm2 at 1.0 VSCE. This enhancement in the photocurrent
      is related to the synergistic effects of Ag decoration, nitrogen doping, and the
      unique structural properties of the fabricated nanotube arrays.

PMID- 28507304
TI  - Thickness-dependent conductance in Sb2SeTe2 topological insulator nanosheets.
AB  - The conductivity increases as thickness decreases in a series of Sb2SeTe2
      topological insulator nanosheets with thickness ranging from 80 to 200 nm, where
      the sheet conductance is proportional to the thickness. The corresponding sheet
      conductance of the surface state is 8.7 e2/h which is consistent with the values
      extracted from the temperature dependent Shubnikov-de Haas oscillations at high
      magnetic fields. The extracted Fermi momentum is the same as the results from the
      ARPES value, and the Berry phase is pi. These support that the thickness
      dependent sheet conductance originates from the combination of the surface state
      and the bulk state.

PMID- 28507305
TI  - Overcoming thermal noise in non-volatile spin wave logic.
AB  - Spin waves are propagating disturbances in magnetically ordered materials,
      analogous to lattice waves in solid systems and are often described from a
      quasiparticle point of view as magnons. The attractive advantages of Joule-heat
      free transmission of information, utilization of the phase of the wave as an
      additional degree of freedom and lower footprint area compared to conventional
      charge-based devices have made spin waves or magnon spintronics a promising
      candidate for beyond-CMOS wave-based computation. However, any practical
      realization of an all-magnon based computing system must undergo the essential
      steps of a careful selection of materials and demonstrate robustness with respect
      to thermal noise or variability. Here, we aim at identifying suitable materials
      and theoretically demonstrate the possibility of achieving error-free clocked non
      volatile spin wave logic device, even in the presence of thermal noise and clock
      jitter or clock skew.

PMID- 28507306
TI  - Long-term increases in soil carbon due to ecosystem fertilization by atmospheric
      nitrogen deposition demonstrated by regional-scale modelling and observations.
AB  - Fertilization of nitrogen (N)-limited ecosystems by anthropogenic atmospheric
      nitrogen deposition (Ndep) may promote CO2 removal from the atmosphere, thereby
      buffering human effects on global radiative forcing. We used the biogeochemical
      ecosystem model N14CP, which considers interactions among C (carbon), N and P
      (phosphorus), driven by a new reconstruction of historical Ndep, to assess the
      responses of soil organic carbon (SOC) stocks in British semi-natural landscapes
      to anthropogenic change. We calculate that increased net primary production due
      to Ndep has enhanced detrital inputs of C to soils, causing an average increase
      of 1.2 kgCm-2 (c. 10%) in soil SOC over the period 1750-2010. The simulation
      results are consistent with observed changes in topsoil SOC concentration in the
      late 20th Century, derived from sample-resample measurements at nearly 2000 field
      sites. More than half (57%) of the additional topsoil SOC is predicted to have a
      short turnover time (c. 20 years), and will therefore be sensitive to future
      changes in Ndep. The results are the first to validate model predictions of Ndep
      effects against observations of SOC at a regional field scale. They demonstrate
      the importance of long-term macronutrient interactions and the transitory nature
      of soil responses in the terrestrial C cycle.

PMID- 28507307
TI  - A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC.
AB  - Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is
      interest in evaluating alternate dosing schedules and novel combinations of pano
      for the treatment of upper aerodigestive and lung malignancies; thus we evaluated
      it in combination with Taxol, a chemotherapeutic with activity in both diseases.
      Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and
      Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to
      senescence rather than potentiation of cell death. Senescence occurred following
      cisplatin- or Taxol-treatment in cell lines from both cancer types and was
      associated with decreased histone 3 (H3) acetylation and increased Bcl-xL
      expression: the latter a biomarker of senescence and target of anti-senescence
      therapeutics, or senolytics. Since H3 acetylation and Bcl-xL expression were
      altered in senescence, we subsequently evaluated pano as a senolytic in
      chemotherapy-treated cancer cells enriched for senescent cells. Pano caused cell
      death at significantly higher rates compared to repeat dosing with chemotherapy.
      This was associated with decreased expression of Bcl-xL and increased acetylated
      H3, reversing the expression patterns observed in senescence. These data support
      evaluating pano as a post-chemotherapy senolytic with the potential to kill
      persistent senescent cells that accumulate during standard chemotherapy in NSCLC
      and HNSCC.

PMID- 28507308
TI  - Barriers to breastfeeding in Lebanon: A policy analysis.
AB  - Although the issue of breastfeeding in Lebanon has risen on the political agenda,
      the country does not meet international recommendations for early breastfeeding
      practices. This study analysed barriers to dissemination, implementation, and
      enforcement of key policies to improve early breastfeeding practices. We
      conducted interviews with stakeholders in breastfeeding policy in Lebanon and
      used a framework approach for analysing data. We found a disconnect between
      policy endorsement and translation on the ground, weak engagement of professional
      associations and governmental institutions, undue influence by the breast milk
      substitute industry, and competing priorities-most notably the current refugee
      crisis. This study highlights the potential policy opportunities to counter these
      barriers and points to the role of international organisations and grassroots
      advocacy in pushing, monitoring, and implementing policies that protect
      breastfeeding, where government capacity is limited, and the private sector is
      strong.

PMID- 28507309
TI  - PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia.
AB  - The gene of protein interacting with C kinase 1 alpha (PICK1) has been implicated
      in schizophrenia, nevertheless, conflicting results existed. However, its role in
      cognitive function remains unclear. Besides, cognitive deficits impair the long
      term outcome. We explored whether the polymorphisms of PICK1 (rs2076369, rs3952)
      affected cognitive functions in schizophrenic patients. We analyzed 302 patients
      and tested the differences of cognitive functions, clinical symptoms between
      genetic groups. We also used general linear model to analyze the effect of PICK1
      genetic polymorphisms on cognitive functions. After adjustment for gender, age,
      education, the patients with rs2076369 G/T genotype showed better performance
      than T/T homozygotes in the summary score, global composite score, neurocognitive
      composite score, category fluency subtest, WAIS-III-Digit Symbol Coding subtest,
      working memory, WMS-III-Spatial Span (backward) subtest, MSCEIT-managing emotions
      branch (p = 0.038, 0.025, 0.046, 0.036, 0.025, 0.027, 0.035, 0.028,
      respectively). G/G homozygotes performed better than T/T in category fluency
      subtest (p = 0.049). A/A homozygotes of rs3952 performed better than G/G in trail
      making A subtest (p = 0.048). To our knowledge, this is the first study to
      indicate that PICK1 polymorphisms may associate with cognitive functions in
      schizophrenic patients. Further replication studies in healthy controls or other
      ethnic groups are warranted.

PMID- 28507310
TI  - Molecular and functional characterization of the BMPR2 gene in Pulmonary Arterial
      Hypertension.
AB  - Pulmonary arterial hypertension is a progressive disease that causes the
      obstruction of precapillary pulmonary arteries and a sustained increase in
      pulmonary vascular resistance. The aim was to analyze functionally the variants
      found in the BMPR2 gene and to establish a genotype-phenotype correlation. mRNA
      expression studies were performed using pSPL3 vector, studies of subcellular
      localization were performed using pEGFP-N1 vector and luciferase assays were
      performed using pGL3-Basic vector. We have identified 30 variants in the BMPR2
      gene in 27 of 55 patients. In 16 patients we detected pathogenic mutations.
      Minigene assays revealed that 6 variants (synonymous, missense) result in
      splicing defect. By immunofluorescence assay, we observed that 4 mutations affect
      the protein localization. Finally, 4 mutations located in the 5'UTR region showed
      a decreased transcriptional activity in luciferase assays. Genotype-phenotype
      correlation, revealed that patients with pathogenic mutations have a more severe
      phenotype (sPaP p = 0.042, 6MWT p = 0.041), a lower age at diagnosis (p = 0.040)
      and seemed to have worse response to phosphodiesterase-5-inhibitors (p = 0.010).
      Our study confirms that in vitro expression analysis is a suitable approach in
      order to investigate the phenotypic consequences of the nucleotide variants,
      especially in cases where the involved genes have a pattern of expression in
      tissues of difficult access.

PMID- 28507311
TI  - Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and
      sensitizes DDP treatment.
AB  - Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression,
      and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and
      renders a therapeutic interference option to lung cancer patients with poor
      prognosis. In this study, we screened and evaluated the specificity of a Chinese
      herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling
      pathway to block NSCLC progression. Our study confirmed that aberrant activation
      of the SHH signal pathway conferred more proliferative and invasive phenotypes to
      human lung cancer cells. This study revealed that SBE specifically repressed SHH
      signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis
      via arresting cell cycle progression. We also found that SBE significantly
      sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH
      components in vitro and in vivo. Mechanistic investigations indicated that SBE
      transcriptionally and specifically downregulated SMO and consequently attenuated
      the activities of GLI1 and its downstream targets in SHH signaling pathway, which
      interacted with cell cycle checkpoint enzymes to arrest cell cycle progression
      and lead to cellular growth inhibition and migration blockade. Collectively, our
      results suggest SBE as a novel drug candidate for NSCLC which specifically and
      sensitively targets SHH signaling pathway.

PMID- 28507312
TI  - Design and evaluation of EphrinA1 mutants with cerebral protective effect.
AB  - The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood
      brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in
      ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective
      agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4,
      respectively. The computational analysis showed that these four mutants were
      capable of interacting with EphA2. Their potential neuroprotective effects were
      examined in mouse focal ischemia/reperfusion (I/R) model. EM2 exhibited strong
      neuroprotective effects, including reduced brain infarct volume, neuronal
      apoptosis, cerebral edema, and improved neurological scores. The EM2-mediated
      protection was associated with a comparative decrease in BBB leakage,
      inflammatory infiltration, and higher expression levels of tight junction
      proteins, such as zonula occludens-1 and Occludin. I/R-induced high expression of
      Rho-associated protein kinase 2 (ROCK2) was down-regulated after EM2 treatment.
      Moreover, EM2 reduced agonist doxazosin-induced EphA2 phosphorylation and cells
      rounding in PC3 cells, indicating EphA2-antagonizing activity of EM2. These
      finding provided evidences of the neuroprotection of EphA2 antagonist and a novel
      approach for ischemic stroke treatment. These results also suggested that a
      receptor agonist can be switched to an antagonist by substituting one or more
      relevant residues.

PMID- 28507313
TI  - Chronic intrahypothalamic rather than subcutaneous liraglutide treatment reduces
      body weight gain and stimulates the melanocortin receptor system.
AB  - BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity
      treatment where it induces body weight reduction possibly via the hypothalamus,
      which regulates energy homeostasis. In animal studies, acute liraglutide
      treatment triggers satiety, weight loss and activates thermogenesis in adipose
      tissue. However, the precise mechanisms how liraglutide affects in particular
      chronic weight loss are still under investigation. OBJECTIVES: We aimed to
      evaluate whether chronic hypothalamic or chronic subcutaneous administration of
      liraglutide induces sustained weight loss through altered adipose tissue function
      and to what extent hypothalamic neuronal appetite regulators are involved in the
      liraglutide-induced weight loss in healthy lean rats on a normal diet.
      MATERIALS/METHODS: We continuously administered liraglutide either
      intrahypothalamically (10 MUg per day) or subcutaneously (200 MUg kg-1 per day)
      for 28 days to lean Sprague Dawley rats (n=8 each). We assessed changes in body
      weight, adipose tissue mass, adipocyte size and adipose tissue volume in the
      abdominal region by using micro-CT. We analyzed genetic expression patterns of
      browning, thermogenic and adipocyte differentiation regulators in adipose tissues
      as well as particular neuronal appetite regulators in the hypothalamus. RESULTS:
      Intrahypothalamic liraglutide administration induced an 8% body weight reduction
      at day 9 compared with the control group (P<0.01) and a 7% body weight loss at
      day 9 compared with subcutaneous liraglutide treatment (P<0.01), supported by a
      significant reduction in adipose tissue mass and volume with intrahypothalamic
      liraglutide administration (P<0.05). Our data show that chronic intrahypothalamic
      liraglutide treatment triggered an 18-fold induction of the hypothalamic mc4r
      gene (P<0.01) accompanied by a significant increase in circulating thyroxine (T4)
      levels (P<0.05). CONCLUSIONS: Chronic intrahypothalamic liraglutide
      administration resulted in a profound reduction in body weight and fat mass loss
      most likely mediated by the hypothalamic melanocortin system rather than by
      adipose tissue browning or improved thermogenesis.

PMID- 28507314
TI  - Metabolic imaging of energy metabolism in traumatic brain injury using
      hyperpolarized [1-13C]pyruvate.
AB  - Traumatic brain injury (TBI) is known to cause perturbations in the energy
      metabolism of the brain, but current tests of metabolic activity are only
      indirect markers of energy use or are highly invasive. Here we show that
      hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as
      a direct, non-invasive method for studying the effects of TBI on energy
      metabolism. Measurements were performed on rats with moderate TBI induced by
      controlled cortical impact on one cerebral hemisphere. Following injection of
      hyperpolarized [1-13C]pyruvate, the resulting 13C-bicarbonate signal was found to
      be 24 +/- 6% lower in the injured hemisphere compared with the non-injured
      hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 +/- 8%
      lower in the injured hemisphere. In a control group, no significant difference in
      signal was found between sides of the brain. The results suggest an impairment in
      mitochondrial pyruvate metabolism, resulting in a decrease in aerobic respiration
      at the location of injury following TBI.

PMID- 28507315
TI  - The Herpesvirus Nuclear Egress Complex Component, UL31, Can Be Recruited to Sites
      of DNA Damage Through Poly-ADP Ribose Binding.
AB  - The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the
      herpesvirus nuclear egress complex that not only functions in the egress of DNA
      containing capsids from the nucleus, but is also required for optimal replication
      of viral DNA and its packaging into capsids. Here we report that the UL31 protein
      from HSV-2 can be recruited to sites of DNA damage by sequences found in its N
      terminus. The N-terminus of UL31 contains sequences resembling a poly (ADP
      ribose) (PAR) binding motif suggesting that PAR interactions might mediate UL31
      recruitment to damaged DNA. Whereas PAR polymerase inhibition prevented UL31
      recruitment to damaged DNA, inhibition of signaling through the ataxia
      telangiectasia mutated DNA damage response pathway had no effect. These findings
      were further supported by experiments demonstrating direct and specific
      interaction between HSV-2 UL31 and PAR using purified components. This study
      reveals a previously unrecognized function for UL31 and may suggest that the
      recognition of PAR by UL31 is coupled to the nuclear egress of herpesvirus
      capsids, influences viral DNA replication and packaging, or possibly modulates
      the DNA damage response mounted by virally infected cells.

PMID- 28507316
TI  - Autism spectrum disorders and autistic traits share genetics and biology.
AB  - Autism spectrum disorders (ASDs) and autistic traits in the general population
      may share genetic susceptibility factors. In this study, we investigated such
      potential overlap based on common genetic variants. We developed and validated a
      self-report questionnaire of autistic traits in adults. We then conducted genome
      wide association studies (GWASs) of six trait scores derived from the
      questionnaire through exploratory factor analysis in 1981 adults from the general
      population. Using the results from the Psychiatric Genomics Consortium GWAS of
      ASDs, we observed genetic sharing between ASDs and the autistic traits 'childhood
      behavior', 'rigidity' and 'attention to detail'. Gene-set analysis subsequently
      identified 'rigidity' to be significantly associated with a network of ASD gene
      encoded proteins that regulates neurite outgrowth. Gene-wide association with the
      well-established ASD gene MET reached significance. Taken together, our findings
      provide evidence for an overlapping genetic and biological etiology underlying
      ASDs and autistic population traits, which suggests that genetic studies in the
      general population may yield novel ASD genes.

PMID- 28507317
TI  - Elevation of p11 in lateral habenula mediates depression-like behavior.
AB  - The lateral habenula (LHb) is a key brain region involved in the pathophysiology
      of depression. It is activated by stimuli associated with negative experiences
      and is involved in encoding aversive signals. Hyperactivity of LHb is found in
      both rodent models of depression and human patients with depression. However,
      little is known about the underlying molecular mechanisms. Here we show that in
      LHb neurons, p11, a multifunctional protein implicated in depression, is
      significantly upregulated by chronic restraint stress. Knockdown of p11
      expression in LHb alleviates the stress-induced depression-like behaviors.
      Moreover, chronic restraint stress induces bursting action potentials in LHb
      neurons, which are abolished by p11 knockdown. Overexpression of p11 in dopamine
      D2 receptor-containing LHb neurons of control mice induces depression-like
      behaviors. These results have identified p11 in LHb as a key molecular
      determinant regulating negative emotions, which may help to understand the
      molecular and cellular basis of depression.

PMID- 28507319
TI  - Longitudinal changes of tau PET imaging in relation to hypometabolism in
      prodromal and Alzheimer's disease dementia.
AB  - The development of tau-specific positron emission tomography (PET) tracers allows
      imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD)
      and other tauopathies. Eighteen patients with baseline investigations enroled in
      a 17-month follow-up study, including 16 with AD (10 had mild cognitive
      impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD
      dementia) and two with corticobasal syndrome. All patients underwent PET scans
      with [18F]THK5317 (tau deposition) and [18F]FDG (glucose metabolism) at baseline
      and follow-up, neuropsychological assessment at baseline and follow-up and a scan
      with [11C]PIB (amyloid-beta deposition) at baseline only. At a group level,
      patients with AD (prodromal or dementia) showed unchanged [18F]THK5317 retention
      over time, in contrast to significant decreases in [18F]FDG uptake in
      temporoparietal areas. The pattern of changes in [18F]THK5317 retention was
      heterogeneous across all patients, with qualitative differences both between the
      two AD groups (prodromal and dementia) and among individual patients. High
      [18F]THK5317 retention was significantly associated over time with low episodic
      memory encoding scores, while low [18F]FDG uptake was significantly associated
      over time with both low global cognition and episodic memory encoding scores.
      Both patients with corticobasal syndrome had a negative [11C]PIB scan, high
      [18F]THK5317 retention with a different regional distribution from that in AD,
      and a homogeneous pattern of increased [18F]THK5317 retention in the basal
      ganglia over time. These findings highlight the heterogeneous propagation of tau
      pathology among patients with symptomatic AD, in contrast to the homogeneous
      changes seen in glucose metabolism, which better tracked clinical progression.

PMID- 28507318
TI  - Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a
      multisite mega-analysis of 983 patients and 1349 healthy controls.
AB  - Although cerebellar involvement across a wide range of cognitive and
      neuropsychiatric phenotypes is increasingly being recognized, previous large
      scale studies in schizophrenia (SZ) have primarily focused on supratentorial
      structures. Hence, the across-sample reproducibility, regional distribution,
      associations with cerebrocortical morphology and effect sizes of cerebellar
      relative to cerebral morphological differences in SZ are unknown. We addressed
      these questions in 983 patients with SZ spectrum disorders and 1349 healthy
      controls (HCs) from 14 international samples, using state-of-the-art image
      analysis pipelines optimized for both the cerebellum and the cerebrum. Results
      showed that total cerebellar grey matter volume was robustly reduced in SZ
      relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar
      regions showing functional connectivity with frontoparietal cortices (d=-0.40).
      Effect sizes for cerebellar volumes were similar to the most consistently
      reported cerebral structural changes in SZ (e.g., hippocampus volume and
      frontotemporal cortical thickness), and were highly consistent across samples.
      Within groups, we further observed positive correlations between cerebellar
      volume and cerebral cortical thickness in frontotemporal regions (i.e.,
      overlapping with areas that also showed reductions in SZ). This cerebellocerebral
      structural covariance was strongest in SZ, suggesting common underlying disease
      processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar
      volume reduction in SZ was highly consistent across the included age span (16-66
      years) and present already in the youngest patients, a finding that is more
      consistent with neurodevelopmental than neurodegenerative etiology. Taken
      together, these novel findings establish the cerebellum as a key node in the
      distributed brain networks underlying SZ.

PMID- 28507320
TI  - The microbiome regulates amygdala-dependent fear recall.
AB  - The amygdala is a key brain region that is critically involved in the processing
      and expression of anxiety and fear-related signals. In parallel, a growing number
      of preclinical and human studies have implicated the microbiome-gut-brain in
      regulating anxiety and stress-related responses. However, the role of the
      microbiome in fear-related behaviours is unclear. To this end we investigated the
      importance of the host microbiome on amygdala-dependent behavioural readouts
      using the cued fear conditioning paradigm. We also assessed changes in neuronal
      transcription and post-transcriptional regulation in the amygdala of naive and
      stimulated germ-free (GF) mice, using a genome-wide transcriptome profiling
      approach. Our results reveal that GF mice display reduced freezing during the
      cued memory retention test. Moreover, we demonstrate that under baseline
      conditions, GF mice display altered transcriptional profile with a marked
      increase in immediate-early genes (for example, Fos, Egr2, Fosb, Arc) as well as
      genes implicated in neural activity, synaptic transmission and nervous system
      development. We also found a predicted interaction between mRNA and specific
      microRNAs that are differentially regulated in GF mice. Interestingly, colonized
      GF mice (ex-GF) were behaviourally comparable to conventionally raised (CON)
      mice. Together, our data demonstrates a unique transcriptional response in GF
      animals, likely because of already elevated levels of immediate-early gene
      expression and the potentially underlying neuronal hyperactivity that in turn
      primes the amygdala for a different transcriptional response. Thus, we
      demonstrate for what is to our knowledge the first time that the presence of the
      host microbiome is crucial for the appropriate behavioural response during
      amygdala-dependent memory retention.

PMID- 28507321
TI  - PET imaging of dopamine-D2 receptor internalization in schizophrenia.
AB  - Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)
      D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and
      preclinical studies have shown agonist-induced D2R internalization can be imaged
      with positron emission tomography (PET) using D2R radiotracers combined with
      psychostimulant challenge. This is feasible if radiotracer binding is measured
      when postchallenge DA levels have returned to baseline, following the initial
      competition phase between DA and radiotracer for binding to D2R. Here we used
      'late-phase' imaging after challenge to test the hypothesis that impaired D2R
      internalization in SZ leads to blunted late-phase displacement, or a faster
      return to baseline, in patients compared with healthy controls (HCs). We imaged
      10 patients with SZ and 9 HCs with PET and [11C]raclopride at baseline and two
      times (3-5 and 6-10 h) following 0.5 mg kg-1 dextroamphetamine. We measured
      binding potential relative to non-displaceable compartment (BPND) and derived
      percent reduction from baseline (DeltaBPND) for each postamphetamine scan. To
      test the hypothesis that time course of return of striatal BPND to baseline
      differed between SZ and HCs, we implemented a linear model with DeltaBPND as
      dependent variable, time after amphetamine as repeated measure and time after
      amphetamine and diagnostic group as fixed effects. Neither diagnostic group nor
      interaction of diagnostic group-by-time after amphetamine significantly affected
      striatal DeltaBPND (F=1.38, P=0.26; F=0.51, P=0.61). These results show similar
      pattern of return of BPND to baseline as a function of time in patients with SZ
      and HC, suggesting that striatal D2R internalization as measured by our imaging
      paradigm is normal in patients with SZ.

PMID- 28507323
TI  - Increasing phenological asynchrony between spring green-up and arrival of
      migratory birds.
AB  - Consistent with a warming climate, birds are shifting the timing of their
      migrations, but it remains unclear to what extent these shifts have kept pace
      with the changing environment. Because bird migration is primarily cued by
      annually consistent physiological responses to photoperiod, but conditions at
      their breeding grounds depend on annually variable climate, bird arrival and
      climate-driven spring events would diverge. We combined satellite and citizen
      science data to estimate rates of change in phenological interval between spring
      green-up and migratory arrival for 48 breeding passerine species across North
      America. Both arrival and green-up changed over time, usually in the same
      direction (earlier or later). Although birds adjusted their arrival dates, 9 of
      48 species did not keep pace with rapidly changing green-up and across all
      species the interval between arrival and green-up increased by over half a day
      per year. As green-up became earlier in the east, arrival of eastern breeding
      species increasingly lagged behind green-up, whereas in the west-where green-up
      typically became later-birds arrived increasingly earlier relative to green-up.
      Our results highlight that phenologies of species and trophic levels can shift at
      different rates, potentially leading to phenological mismatches with negative
      fitness consequences.

PMID- 28507322
TI  - Rapid susceptibility profiling of carbapenem-resistant Klebsiella pneumoniae.
AB  - The expanding global distribution of multi-resistant Klebsiella pneumoniae
      demands faster antimicrobial susceptibility testing (AST) to guide antibiotic
      treatment. Current ASTs rely on time-consuming differentiation of resistance and
      susceptibility after initial isolation of bacteria from a clinical specimen. Here
      we describe a flow cytometry workflow to determine carbapenem susceptibility from
      bacterial cell characteristics in an international K. pneumoniae isolate
      collection (n = 48), with a range of carbapenemases. Our flow cytometry-assisted
      susceptibility test (FAST) method combines rapid qualitative susceptible/non
      susceptible classification and quantitative MIC measurement in a single process
      completed shortly after receipt of a primary isolate (54 and 158 minutes
      respectively). The qualitative FAST results and FAST-derived MIC (MICFAST)
      correspond closely with broth microdilution MIC (MICBMD, Matthew's correlation
      coefficient 0.887), align with the international AST standard (ISO 200776-1;
      2006) and could be used for rapid determination of antimicrobial susceptibility
      in a wider range of Gram negative and Gram positive bacteria.

PMID- 28507325
TI  - Corrigendum: Characterisation of mental health conditions in social media using
      Informed Deep Learning.

PMID- 28507326
TI  - Tunability of Band Gap and Photoluminescence in CH3NH3PbI3 Films by Anodized
      Aluminum Oxide Templates.
AB  - Hybrid organic-inorganic halide CH3NH3PbI3 perovskite films are deposited on
      anodized aluminum oxide templates with the different pore diameters via one-step
      spin coating method. The obvious 0.082 eV blue shift of optical band gap is
      observed in films with decreasing the diameters of pores from 400 to 30 nm. And
      numerical simulations based on finite element modeling are carried out to
      represent the absorption edge and consistent with the experiment results. It is
      interesting that the films show the intense photoluminescence with the excitation
      intensity of less than 1 MUW. Moreover, the photoluminescence intensity is
      increased with increasing pore diameters, which is attributed to the radiative
      recombination rate of photogenerated electrons and holes. These results pave a
      way for the further understanding of tunable photophysical properties of
      perovskite films.

PMID- 28507324
TI  - A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF
      alpha and TGF-beta1 pathways.
AB  - Renal fibrosis is closely related to chronic inflammation and is under the
      control of epigenetic regulations. Because the signaling of transforming growth
      factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) play key
      roles in progression of renal fibrosis, dual blockade of TGF-beta1 and TNF-alpha
      is desired as its therapeutic approach. Here we screened small molecules showing
      anti-TNF-alpha activity in the compound library of indole derivatives. 11 out of
      41 indole derivatives inhibited the TNF-alpha effect. Among them, Mitochonic Acid
      35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent
      effect. The anti-TNF-alpha activity was mediated by inhibiting IkappaB kinase
      phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in
      the mice. Additionally, MA-35 concurrently showed an anti-TGF-beta1 effect by
      inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-beta1
      induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney,
      which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis
      with the downregulation of inflammatory cytokines and fibrotic gene expressions.
      Furthermore, MA-35 inhibited TGF-beta1-induced H3K4me1 histone modification of
      the fibrotic gene promoter, leading to a decrease in the fibrotic gene
      expression. MA-35 affects multiple signaling pathways involved in the fibrosis
      and may recover epigenetic modification; therefore, it could possibly be a novel
      therapeutic drug for fibrosis.

PMID- 28507327
TI  - PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell
      properties in pancreatic ductal adenocarcinoma.
AB  - Recurrence following chemotherapy is observed in the majority of patients with
      pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem
      cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an
      efficient approach to targeting pancreatic CSCs remains to be established. Here
      we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)
      dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a
      phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the
      Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of
      PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly
      suppressed tumour formation and liver metastasis in vivo. We also found that a
      synthesized EGCG analog capable of inducing strong cGMP production drastically
      suppressed the CSC properties of PDAC and extended the survival period in vivo.
      In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong
      cGMP inducer could be a potential treatment candidate for the eradication of CSCs
      of PDAC.

PMID- 28507328
TI  - Pro-inflammatory Ca++-activated K+ channels are inhibited by hydroxychloroquine.
AB  - Antimalarials have demonstrated beneficial effects in Systemic Lupus
      Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular
      players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ)
      is a known ion channel inhibitor, this property has not been linked to its anti
      inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion
      channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca++
      activated K+ conductance in THP-1 macrophages in a dose-dependent manner. In
      macrophages, ATP-induced K+ efflux plays a key role in activating the NLRP3
      inflammasome. ATP-induced IL-1beta secretion was controlled by the KCa1.1
      inhibitor iberiotoxin. NS1619 and NS309 (KCa1.1 and KCa3.1 activators
      respectively) induced the secretion of IL-1beta. This effect was inhibited by HCQ
      and also by iberiotoxin and clotrimazol (KCa3.1 inhibitor), arguing against off
      target effect. In vitro, HCQ inhibited IL-1beta and caspase 1 activation induced
      by ATP in a dose-dependent manner. HCQ impaired K+ efflux induced by ATP. In
      vivo, HCQ inhibited caspase 1-dependent ATP-induced neutrophil recruitment. Our
      results show that HCQ inhibits Ca++-activated K+ channels. This effect may lead
      to impaired inflammasome activation. These results are the basis for i) a novel
      anti-inflammatory mechanism for HCQ and ii) a new strategy to target pro
      rheumatic Ca++-activated K+ channels.

PMID- 28507329
TI  - Breeding histories and selection criteria for oilseed rape in Europe and China
      identified by genome wide pedigree dissection.
AB  - Selection breeding has played a key role in the improvement of seed yield and
      quality in oilseed rape (Brassica napus L.). We genotyped Tapidor (European),
      Ningyou7 (Chinese) and their progenitors with the Brassica 60 K Illumina Infinium
      SNP array and mapped a total of 29,347 SNP markers onto the reference genome of
      Darmor-bzh. Identity by descent (IBD) refers to a haplotype segment of a
      chromosome inherited from a shared common ancestor. IBDs identified on the C
      subgenome were larger than those on the A subgenome within both the Tapidor and
      Ningyou7 pedigrees. IBD number and length were greater in the Ningyou7 pedigree
      than in the Tapidor pedigree. Seventy nine QTLs for flowering time, seed quality
      and root morphology traits were identified in the IBDs of Tapidor and Ningyou7.
      Many more candidate genes had been selected within the Ningyou7 pedigree than
      within the Tapidor pedigree. These results highlight differences in the transfer
      of favorable gene clusters controlling key traits during selection breeding in
      Europe and China.

PMID- 28507330
TI  - Flatbed epi relief-contrast cellular monitoring system for stable cell culture.
AB  - Consistent cell preparation is a fundamental preliminary step for understanding
      complex cellular mechanisms in various cell-based research fields, including
      basic cell biology, cancer research, and tissue engineering. However, certain
      elusive factors, such as cellular de-differentiation and contamination with
      mycoplasma or other types of cells, have compromised the reproducibility and
      reliability of cell-based approaches. Here, we propose an epi relief-contrast
      cellular monitoring system (eRC-CMS) that allows images of cells in a typical
      culture plate to be acquired, stored, and analysed for daily cell quality
      control. Due to its full flatbed nature and automated system, cells placed at any
      location on the stage can be analysed without special attention. Using this
      system, changes in the size, circularity, and proliferation of endothelial cells
      in subculture were recorded. Analyses of images of ~9,930,000 individual cells
      revealed that the growth activity and cell circularity in subcultures were
      closely correlated with their angiogenic activity in a subsequent hydrogel assay,
      demonstrating that eRC-CMS is useful for assessing cell quality in advance. We
      further demonstrated that eRC-CMS was feasible for the imaging of neurite
      elongation and spheroid formation. This system may provide a robust and versatile
      approach for daily cell preparation to facilitate reliable and reproducible cell
      based studies.

PMID- 28507331
TI  - Mycoviruses of an endophytic fungus can replicate in plant cells: evolutionary
      implications.
AB  - So far there is no record of a specific virus able to infect both fungal and
      plant hosts in nature. However, experimental evidence shows that some plant virus
      RdRPs are able to perform replication in trans of genomic or DI RNAs in the yeast
      Saccharomyces cerevisiae. Furthermore, tobacco mosaic virus was recently shown to
      replicate in a filamentous ascomycetous fungus. Thus, at least experimentally,
      some plant viruses can infect some fungi. Endophytic fungi have been reported
      from many plants and several of these fungi have been shown to contain viruses.
      Here we tested if mycoviruses derived from a marine plant endophyte can replicate
      in plant cells. For this purpose, we used partially purified viral particles from
      isolate MUT4330 of Penicillium aurantiogriseum var. viridicatum which harbors six
      virus species, some having dsRNA and some positive-strand ssRNA genomes. These
      were transfected into three distinct plant protoplast cell systems. Time-course
      analysis of absolute RNA accumulation provided for the first time evidence that
      viruses of two species belonging to the Partitiviridae and Totiviridae families,
      can replicate in plant cells without evidence of host adaptation, i.e, changes in
      their nucleotide sequence.

PMID- 28507333
TI  - Janus monolayers of transition metal dichalcogenides.
AB  - Structural symmetry-breaking plays a crucial role in determining the electronic
      band structures of two-dimensional materials. Tremendous efforts have been
      devoted to breaking the in-plane symmetry of graphene with electric fields on AB
      stacked bilayers or stacked van der Waals heterostructures. In contrast,
      transition metal dichalcogenide monolayers are semiconductors with intrinsic in
      plane asymmetry, leading to direct electronic bandgaps, distinctive optical
      properties and great potential in optoelectronics. Apart from their in-plane
      inversion asymmetry, an additional degree of freedom allowing spin manipulation
      can be induced by breaking the out-of-plane mirror symmetry with external
      electric fields or, as theoretically proposed, with an asymmetric out-of-plane
      structural configuration. Here, we report a synthetic strategy to grow Janus
      monolayers of transition metal dichalcogenides breaking the out-of-plane
      structural symmetry. In particular, based on a MoS2 monolayer, we fully replace
      the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly
      by means of scanning transmission electron microscopy and energy-dependent X-ray
      photoelectron spectroscopy, and prove the existence of vertical dipoles by second
      harmonic generation and piezoresponse force microscopy measurements.

PMID- 28507332
TI  - A solid-state single-photon filter.
AB  - A strong limitation of linear optical quantum computing is the probabilistic
      operation of two-quantum-bit gates based on the coalescence of indistinguishable
      photons. A route to deterministic operation is to exploit the single-photon
      nonlinearity of an atomic transition. Through engineering of the atom-photon
      interaction, phase shifters, photon filters and photon-photon gates have been
      demonstrated with natural atoms. Proofs of concept have been reported with
      semiconductor quantum dots, yet limited by inefficient atom-photon interfaces and
      dephasing. Here, we report a highly efficient single-photon filter based on a
      large optical nonlinearity at the single-photon level, in a near-optimal quantum
      dot cavity interface. When probed with coherent light wavepackets, the device
      shows a record nonlinearity threshold around 0.3 +/- 0.1 incident photons. We
      demonstrate that 80% of the directly reflected light intensity consists of a
      single-photon Fock state and that the two- and three-photon components are
      strongly suppressed compared with the single-photon one.

PMID- 28507334
TI  - Energy-dependent path of dissipation in nanomechanical resonators.
AB  - Energy decay plays a central role in a wide range of phenomena, such as optical
      emission, nuclear fission, and dissipation in quantum systems. Energy decay is
      usually described as a system leaking energy irreversibly into an environmental
      bath. Here, we report on energy decay measurements in nanomechanical systems
      based on multilayer graphene that cannot be explained by the paradigm of a system
      directly coupled to a bath. As the energy of a vibrational mode freely decays,
      the rate of energy decay changes abruptly to a lower value. This finding can be
      explained by a model where the measured mode hybridizes with other modes of the
      resonator at high energy. Below a threshold energy, modes are decoupled,
      resulting in comparatively low decay rates and giant quality factors exceeding 1
      million. Our work opens up new possibilities to manipulate vibrational states,
      engineer hybrid states with mechanical modes at completely different frequencies,
      and to study the collective motion of this highly tunable system.

PMID- 28507336
TI  - Divergent functional isoforms drive niche specialisation for nutrient acquisition
      and use in rumen microbiome.

PMID- 28507335
TI  - BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-beta
      Smad2/3 pathway.
AB  - Fibrosis is an important, structurally damaging event that occurs in pathological
      cardiac remodeling, leading to cardiac dysfunction. BNIP3L is up-regulated in
      pressure overload-induced heart failure and has been reported to play an
      important role in cardiomyocyte apoptosis; however, its involvement in cardiac
      fibroblasts (CFs) remains unknown. We prove for the first time that the
      expression of BNIP3L is significantly increased in the CFs of rats undergoing
      pressure overload-induced heart failure. Furthermore, this increased BNIP3L
      expression was confirmed in cultured neonatal rat CFs undergoing proliferation
      and extracellular matrix (ECM) protein over-expression that was induced by
      norepinephrine (NE). The overexpression or suppression of BNIP3L promoted or
      inhibited NE-induced proliferation and ECM expression in CFs, respectively. In
      addition, [Ca2+]i, transforming growth factor beta (TGF-beta) and the nuclear
      accumulation of Smad2/3 were successively increased when BNIP3L was overexpressed
      and reduced when BNIP3L was inhibited. Furthermore, the down-regulation of TGF
      beta by TGF-beta-siRNA attenuated the increase of BNIP3L-induced fibronectin
      expression. We also demonstrated that the increase of BNIP3L in CFs was regulated
      by NE-AR-PKC pathway in vitro and in vivo. These results reveal that BNIP3L is a
      novel mediator of pressure overload-induced cardiac fibrosis through the [Ca2+]i
      TGF-beta-Smad2/3 pathway in CFs.

PMID- 28507338
TI  - Impact of Trace Minerals on Wound Healing of Footpad Dermatitis in Broilers.
AB  - Footpad dermatitis (FPD) is used in the poultry industry as an animal welfare
      criterion to determine stocking density. Trace minerals (TM) play a role in skin
      integrity and wound healing. This study evaluated the impact of TM on FPD and
      consisted of 3 treatments supplemented with 0 (NTM), low (LTM) and high (HTM) TM
      levels in the same basal diet. On d21, 71% birds in all treatments developed mild
      FPD and pens were top-dressed with dry litter to promote FPD healing. Compared to
      NTM, LTM reduced area under the curve (AUC) of FPD lesion scores during d21-42,
      HTM reduced the AUC of FPD lesion scores during d7-21 and d21-42. LTM improved
      growth performance on d14, HTM improved growth performance on d14 and d28. LTM
      and/or HTM increased gene expression of VEGF, TIMP3, TIMP4, MMP13, ITGA2, ITGA3
      and CD40, which promoted collagen synthesis, deposition and organization; cell
      migration, matrix remodeling, and angiogenesis. LTM and/or HTM increased
      inflammation by upregulating TNFalpha and IL-1beta during the early wound healing
      phase and reduced inflammation by downregulating IL-1beta during the late wound
      healing phase. Our findings showed that TM not only improved growth performance
      but also reduced FPD development by promoting FPD wound healing.

PMID- 28507337
TI  - Identification and comparative analysis of the ovarian microRNAs of prolific and
      non-prolific goats during the follicular phase using high-throughput sequencing.
AB  - The kidding rate is one of the most important economic traits for goat
      production, but the genetic mechanism that is associated with ovulation rate is
      poorly understood. Recently, increasing evidence has suggested that microRNAs
      (miRNAs) influence ovarian biological processes. The present study provides the
      first comparison of the ovarian miRNAs of prolific Jintang black goats (JTGs) and
      non-prolific Tibetan goats (TBGs) during the follicular phase using RNA-Seq
      technology. We generated 11.19 million (M) and 11.34 M clean reads from the TBG
      and JTG libraries, respectively, from which a total of 389 known miRNAs were
      identified and 142 novel miRNAs were predicted. A total of 191 miRNAs were
      differentially expressed between the two breeds. Among the 10 most abundant
      miRNAs, miR-21-5p was defined as differentially expressed miRNA with a higher
      level in the JTG library than in the TBG library, but the other miRNAs were not
      different between the breeds. The predicted miRNA-targeted genes were further
      analyzed by Gene Ontology and KEGG pathway analyses. The results revealed that
      miR-21, miR-99a, miRNA-143, let-7f, miR-493 and miR-200b may affect follicular
      development. These findings will increase the current understanding of the role
      of ovarian miRNAs in the regulation of ovulation rate in goats.

PMID- 28507340
TI  - Erratum: Stereopsis deficits in patients with schizophrenia in a Han Chinese
      population.

PMID- 28507339
TI  - Efficacy and tolerability of chemotherapy in Chinese patients with AIDS-related
      Burkitt lymphoma and diffuse large B-cell lymphoma: An observational study.
AB  - We evaluated the efficacy and tolerability of chemotherapy in HIV-infected
      patients with diffuse large B-cell lymphoma (DLBCL) receiving CHOP +/- R (n = 17)
      or Burkitt lymphoma (BL) receiving CODOX-M/IVAC +/- R (n = 15). The study was
      conducted in Beijing Ditan Hospital from January 2009 to August 2015. The
      following grade 4 adverse effects were observed in BL and DLBCL patients,
      respectively: neutropenia (80% versus 47.1%), anaemia (46.7% versus 5.9%),
      thrombocytopenia (53.3% versus 11.8%), bacterial pneumonia (33.3% versus 5.9%),
      and sepsis (20% versus 5.9%) (p < 0.05). In the BL group, 10 (66.7%) patients
      died from treatment-related or tumour-related causes, 5 (33.3%) achieved complete
      response, 1 achieved partial response (6.7%), and 7 developed progressive
      disease. The 1-year overall survival and progression-free survival rates were
      33.3%. Of the DLBCL patients, 3 (17.6%) died from treatment-related causes, 14
      (82.4%) achieved complete response, and 3 had progressive disease. The 1-year
      overall survival and progression-free survival rates were 82.4%. The strongest
      risk factor for death was relapse between chemotherapy cycles (adjusted hazard
      ratio = 47.3; 95%CI, 4.2-528.6, p = 0.002). Initiating antiretroviral therapy
      before chemotherapy failed to improve overall survival. DLBCL patients
      demonstrated good responses and survival outcomes, while BL patients could not
      tolerate chemotherapy due to more severe toxicity, and showed poor responses and
      survival outcomes.

PMID- 28507341
TI  - Increased leukotoxin production: Characterization of 100 base pairs within the
      530 base pair leukotoxin promoter region of Aggregatibacter
      actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) is a major virulence
      factor that kills leukocytes permitting it's escape from host immune
      surveillance. A. actinomycetemcomitans strains can produce high or low levels of
      toxin. Genetic differences reside in the "so called JP2" ltxA promoter region.
      These hyper-leukotoxin producing strains with the 530 bp deletion have been
      studied in detail. However, regions contained within the 530 bp deletion that
      could be responsible for modulation of leukotoxin production have not been
      defined. Here, we report, for the first time, on regions within the 530 bp that
      are responsible for high-levels of ltxA expression. We constructed a deletion of
      530 bps in a primate isolate of A. actinomycetemcomitans, which produced
      leukotoxin equivalent to the JP2 strain. We then constructed sequential deletions
      in regions that span the 530 bps. Results indicated that expression of the ltxA
      transcript was reduced by a potential transcriptional terminator in promoter
      region 298 to 397 with a DeltaG = -7.9 kcal/mol. We also confirmed previous
      findings that transcriptional fusion between the orfX region and ltxC increased
      ltxA expression. In conclusion, we constructed a hyper-leukotoxin producing A.
      actinomycetemcomitans strain and identified a terminator located in the promoter
      region extending from 298-397 that alters ltxA expression.

PMID- 28507342
TI  - Effects of dietary methionine on breast muscle growth, myogenic gene expression
      and IGF-I signaling in fast- and slow-growing broilers.
AB  - This study investigated the responses of fast- (FG) and slow- (SG) growing
      broilers to dietary methionine (Met) status. The broilers were subjected to low
      (LM, 0.38 and 0.28 g/100 g), adequate (AM, 0.51 and 0.42 g/100 g) and high (HM,
      0.65 and 0.52 g/100 g) Met during 1-21 and 22-42 d, respectively. Compared with
      the LM diets, the AM and HM diets increased body weight gain only in the FG
      broilers. The HM diets increased breast muscle yield only in the FG broilers,
      although insulin-like growth factor-I (IGF-I) concentration was increased in both
      strains of broilers. The HM diets increased mRNA levels of myogenic regulatory
      factors (MRF4, Myf5) and myocyte enhancer factor 2 (MEF2A and MEF2B) in the FG
      broilers, and increased MEF2A and decreased myostatin mRNA level in the SG
      broilers. Extracellular signal-regulated kinase (ERK) phosphorylation of breast
      muscle was increased by the HM diets in both strains of broilers, but mechanistic
      target of rapamycin (mTOR) phosphorylation was increased by the AM and HM diets
      only in the FG broilers. These results reflect a strain difference in broiler
      growth and underlying mechanism in response to dietary Met.

PMID- 28507344
TI  - Mesporous 3C-SiC Hollow Fibers.
AB  - In the present work, for the first time, we reported the exploration of
      mesoporous 3C-SiC hollow fibers via single-spinneret electrospinning of
      polyureasilazane (PSN) and polyvinylpyrrolidone (PVP) solution followed by high
      temperature pyrolysis treatment. The resultant products were characterized by X
      ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high
      resolution transmission electron microscopy (HRTEM) and N2 adsorption. The as
      prepared hollow fibers with totally mesoporous walls were uniformly sized in
      diameter and high purity in morphology. They were composed of single-crystalline
      3C-SiC nanoparticles with a surface area of 21.75 m2/g and average pore diameter
      of ~34 nm. The PSN concentration played a determined role on the formation of
      hollow fibers rather than the conventional solid counterparts, enabling their
      growth in a tunable manner. A possible mechanism was proposed for the formation
      of mesoporous SiC hollow fiber.

PMID- 28507343
TI  - Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance
      are exacerbated by TRAIL deletion in mice.
AB  - Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic
      steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and
      cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is
      protective of CVD. We aimed to determine whether TRAIL protects against insulin
      resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail 
      /- mice had increased plasma cholesterol, insulin and glucose compared to
      wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt,
      GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride
      content, inflammation and fibrosis were increased with TRAIL-deletion, with
      elevated expression of genes regulating lipogenesis and gluconeogenesis.
      Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired
      insulin signaling, and >20-fold increased mRNA expression for IL-1beta, IL-6, and
      TNF-alpha. In vitro, palmitate treatment of hepatocytes increased lipid
      accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced.
      TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake.
      Finally, patients with NASH had significantly reduced plasma TRAIL compared to
      control, simple steatosis or obese individuals. These findings suggest that TRAIL
      protects against insulin resistance, NAFLD and vascular inflammation. Increasing
      TRAIL levels may be an attractive therapeutic strategy, to reduce features of
      diabetes, as well as liver and vascular injury, so commonly observed in
      individuals with NAFLD.

PMID- 28507346
TI  - Eliminating wrong blood transfusions - recent advances.

PMID- 28507347
TI  - Performance of TUBEX(r) TF in the diagnosis of enteric fever in private tertiary
      care Hospital Peshawar, Pakistan.
AB  - OBJECTIVE: To evaluate the performance of TUBEX(r) TF in diagnosing enteric
      fever. METHODS: The retrospective study was performed at the Northwest General
      Hospital and Research Centre, Peshawar, Pakistan, and comprised data of all
      patients who had blood cultures and TUBEX(r)TF performed as part of their
      evaluation from April 2011 to November 2015. SPSS 16 was used for data analysis.
      RESULTS: Of the 970 patients, salmonella typhi was isolated in 43(4.43%),
      paratyphi in 9(0.93%) and other organisms in 162(16.7%). TUBEX(r) TF was positive
      in 18(1.86%) cases and negative in 25(2.58%). Of the culture-negative patients,
      TUBEX(r) TF was positive in 35(3.6%) and negative in 136(14%). In cases where no
      organism was cultured, TUBEX(r) TF was positive in 4(0.4%) and negative in
      752(77.5%). The positive predictive value of TUBEX(r) TF was 31.58% and the
      negative predictive value was 97.26%. The sensitivity of TUBEX(r) TF was 41.86%
      while specificity was 95.97%. CONCLUSIONS: TUBEX(r) TF with its low sensitivity
      and positive predictive value was a poor tool for diagnosing enteric fever.

PMID- 28507345
TI  - Genetic variation and phylogeographic structure of the cotton aphid, Aphis
      gossypii, based on mitochondrial DNA and microsatellite markers.
AB  - Aphis gossypii, one of the most important agricultural pests in the world, can
      cause serious economic losses in the main crop-producing areas. To clarify issues
      such as the genetic differentiation, genetic structure, and demographic history
      of A. gossypii populations, we used 10 nuclear microsatellite loci (SSR) and two
      mitochondrial gene sequences (COI and Cytb) to investigate genetic diversity and
      population structure of A. gossypii populations that were collected from 33
      sampling sites in China from different climatic zones. SSR and mtDNA data
      suggested low to moderate levels of genetic diversity. A star-shaped network of
      mtDNA haplotypes indicated that the maternal ancestor of China cotton aphids
      likely originated in Xinjiang. The POPTREE, STRUCTURE and principal coordinate
      analysis (PCoA) revealed two genetic clusters: an eastern and a western region
      group. Isolation by distance (IBD) results showed a positive correlation between
      geographic distance and genetic distance in the vast eastern region but not in
      the western region. Neutrality testing and mismatch distribution analysis
      provided strong evidence for a recent rapid expansion in most populations.
      Genetic bottleneck was not detected in A. gossypii populations of China. The
      present work can help us to develop strategies for managing this pest.

PMID- 28507348
TI  - Microbiological pattern of diabetic foot infections at a tertiary care center in
      a developing country.
AB  - OBJECTIVE: To determine the microbiological profile and antibiotic susceptibility
      patterns of organisms isolated from diabetic foot ulcers in a tertiary care
      hospital Karachi, Pakistan. METHODS: This descriptive study was conducted at the
      Baqai Institute of Diabetology and Endocrinology (BIDE), from January 2013 to
      March 2014. Bone, pus and tissue samples were collected from 342 patients with
      diabetic foot infections and inoculated on appropriate media. Antibiotic
      susceptibility tests were done by Kirby Bauer disk diffusion method. RESULTS: A
      total of 671 aerobic bacteria were isolated from 473 specimens with an average of
      1.45 isolates per specimen. Poly-microbial infection was 56.87%. Gram- negative
      isolates were predominant 76.27%.Staphylococcus aureus was most frequent among
      Gram-positive 20.7% and Escherichia coli 15.72% in Gram negative isolates. MRSA
      was found in 26.76% Staphylococcus aureus. About 33.48% of antimicrobial
      resistant isolates were observed. CONCLUSIONS: In our study, Gram negative
      aerobes were predominant in the diabetic foot infections. A significant number of
      MDR isolates were also observed in this cohort. Delayed referral and
      inappropriate use of broad spectrum antibiotics may be the main cause of increase
      in the frequency of MDR isolates.

PMID- 28507349
TI  - Antibiotics in acute calculous cholecystitis - do Tokyo guidelines influence the
      surgeons' practices?
AB  - OBJECTIVE: To observe changes in surgeons' practice of antibiotic usage in
      patients with acute cholecystitis before and after the implementation of Tokyo
      Guidelines. METHODS: This retrospective, descriptive study was conducted at the
      Aga Khan University Hospital, Karachi, and comprised the medical records of all
      patients with the diagnosis of acute calculus cholecystitis who presented in 2009
      and those who presented in 2014 after the implementation of Tokyo Guidelines. The
      major variables included patients' demographics, antibiotics used and surgical
      outcomes. SPSS 19 was used for data analysis. RESULTS: Of the 356 patients,
      96(27%) were treated in 2009 and 260(73%) in 2014. The overall mean age was
      48.9+/-14 years. There were 185(52%) females and 171(48%) males. Comparison of
      the data from 2 years showed no difference in gender, American Society of
      Anaesthesiologists level, grade of acute cholecystitis and frequency of use of
      empiric antibiotics (p>0.05 each). However, there was significantly less use of
      combination therapy (p=0.00) and metronidazole (p=0.00) in 2014than in 2009.
      Interval cholecystectomy was significantly less practised in 2014 (p=0.03)
      resulting in shorter hospital stay (p=0.00). Despite improvement in antibiotic
      usage practices, post-operative infection rates remained the same in both the
      groups (p=0.58). CONCLUSIONS: Implementation of Tokyo Guidelines not only greatly
      influenced but also standardised the choice of antibiotics in patients without
      compromising the infective and surgical outcomes.

PMID- 28507350
TI  - Amplification of Mitochondrial DNA for detection of Plasmodiumvivax in
      Balochistan.
AB  - OBJECTIVE: To access a new step using PCR to amplify the targeted mtDNA sequence
      for detecting specifically Plasmodium vivax and its co-infections, false positive
      and false negative results with Plasmodium falciparum. METHODS: In this study we
      have standardized a new technical approach in which the target mitochondrial DNA
      sequence (mtDNA) was amplified by using a PCR technique as a tool to detect
      Plasmodium spp. Species specific primers were designed to hybridize with
      cytochrome c oxidase gene of P. vivax (cox I) and P. falciparum (cox III). Two
      hundred blood samples were collected on the basis of clinical symptoms which were
      initially examined through microscopic analysis after preparing Giemsa stained
      thick and thin blood smears. Afterwards genomic DNA was extracted from all
      samples and was then subjected to PCR amplification by using species specific
      primers and amplified segments were sequenced for confirmation of results.
      RESULTS: One-hundred and thirty-two blood samples were detected as positive for
      malaria by PCR, out of which 64 were found to be positive by PCR and 53 by both
      microscopy and PCR for P.vivax infection. Nine samples were found to be false
      negative, one P.vivax mono infection was declared as co infection by PCR and 3
      samples identified as having P.falciparum gametes were confirmed as P.vivax by
      PCR amplification. Sensitivity and specificity were found to be 85% and 92%
      respectively. CONCLUSIONS: Results obtained through PCR method were comparatively
      better and reliable than microscopy.

PMID- 28507351
TI  - Practice of breastfeeding and Immunisation in a periurban community in Pakistan.
AB  - OBJECTIVE: To assess the practice of breastfeeding and immunisation in a peri
      urban community and correlate it with maternal care during pregnancy of the index
      child. METHODS: This community-based, cross-sectional survey was conducted at
      Shifa Tameer-e-Millat University and Shifa College of Medicine, Islamabad,
      Pakistan, from June 2014 to January 2016, using a self-generated questionnaire.
      Systemic random sampling method was used to collect data. SPSS 21 was used to
      analyse the data and to find associations between maternal care and practices of
      breastfeeding. RESULTS: There were 1,275 participants in the study. The mean age
      of the participants was 31.61+/-8.026 years and the mean number of family members
      was 7.28+/-3.42. Overall, 1,121(87.9%) women had exclusively breastfed all their
      children while 906(71.1%) women had their children fully vaccinated. The mean
      duration of exclusive breastfeeding was 5.30+/-1.31 months while the mean
      duration of mixed breastfeeding was 16.70+/-8.62 months. Mothers who were given
      prenatal care were 2.60 and 2.91 times more likely to do exclusive breastfeeding
      and immunisation, respectively, compared to women who were not given prenatal
      care (p<0.05). CONCLUSIONS: There is a dire need to focus more on routine
      services compared to massive immunisation and breastfeeding campaigns.

PMID- 28507352
TI  - Candidiasis: Prevalence and resistance profiling in a tertiary care hospital of
      Pakistan.
AB  - OBJECTIVE: To determine Candida colonisation/infection in renal transplant
      patients and to determine the resistance pattern against antifungal drugs.
      METHODS: This prospective, observational study was conducted at Al-Sayyed
      Hospital, Rawalpindi, Pakistan, from January to October 2014, in collaboration
      with the Microbiology and Public Health Laboratory's, Islamabad campus..The
      clinical specimens investigated included respiratory tract secretions, blood,
      urine, high vaginal swab, skin scrapings, and plastic devices samples. RESULTS:
      Of the 7,850 samples, 164(2.08%) were positive for Candida. Candida albicans were
      most prevalent as they were found in 114(69%) samples. Besides, 56(34%) of the
      positive samples were resistant to one or more antifungal agents. Highest
      resistance was obtained against fluconazole. We found only 5(3.04%) positive
      samples of Candida glabrata; of them, 3(60%)were resistant. In case of Candida
      spp, 27(48%) resistance was observed. In Candida albicans, 23(41%) of the samples
      were found to be resistant. Most of the Candida isolates was recovered from
      bronchial alveolar lavage. CONCLUSIONS: Although Candida albicans remained the
      main responsible species for Candida infections, but non-albican Candida species
      are also emerging.

PMID- 28507353
TI  - Comparison of ketamine-propofol and ketamine-dexmedetomidine combinations in
      children for sedation during tooth extraction.
AB  - OBJECTIVE: To evaluate the efficiency of ketamine-propofol and ketamine
      dexmedetomidine drugs in children for sedation during tooth extraction. METHODS:
      The randomised, prospective study was conducted at the Department of Oral and
      Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, Turkey,
      from September to November 2013, and comprised children who were due to undergo
      tooth extraction. Non-invasive blood pressures (systolic and diastolic),
      peripheral oxygen saturation, heart and respiratory rates and Ramsay Sedation
      Scores were assessed at baseline, after applying the drugs and then every 5
      minutes thereafter. Further, the ketamine-propofol group received 1mg kg-1 of
      ketamine and propofol, and the ketamine-dexmedetomidine group received 1mg kg-1
      of ketamine + 0.5 ug kg1 of dexmedetomidine. RESULTS: Of the 60 participants,
      there were 30 (50%) in each group. No statistically significant differences were
      found in terms of heart rate, non-invasive blood pressures at any time and the
      number of drug repetitions (p>0.05). Nausea-vomiting was statistically higher in
      the ketamine-dexmedetomidine group (p<0.05). CONCLUSIONS: Ketamine-propofol might
      be a better option due to lower vomiting and nausea episodes and higher surgeon
      satisfaction levels.

PMID- 28507354
TI  - The bilobed flap - a better option for soft tissue release in the management of
      Radial Club Hand.
AB  - OBJECTIVE: To establish that the bilobed flap as soft tissue release component
      for the radial club hand is superior to the z-plasty technique in type III and IV
      radial club hands. METHODS: This study was conducted at the Shifa International
      Hospital, Islamabad, Pakistan, from 2009 to 2015, and comprised patients with
      radial club hands operated by a single consultant plastic surgeon. Soft tissue
      release was performed at 08 months. The extremity was then casted for 08 weeks
      and kept in a long-arm cast for 3 to 6 months. RESULTS: Twelve radial club hands
      of 9 patients treated successfully during the study period showed good to
      excellent results. Z-plasty was used on the radial side to correct the soft
      tissue deficiency in 5(42%) hands, and a bilobed flap in 7(58%) hands for soft
      tissue rearrangement on the radial side. Of all hands, 1(8.3%) z-plasty flap
      developed partial flap necrosis and 1(8.3%) each developed infection and needed
      implant (Kirschner wire removal), which were dealt with efficiently with no long
      term sequelae. CONCLUSIONS: The bilobed flap was found to be superior to the z
      plastytechnique since the flap had better predictability and no tissue was
      wasted.

PMID- 28507355
TI  - Estimation of uncertainty measurement - A prerequisite of ISO1589 accreditation
      for clinical laboratories.
AB  - OBJECTIVE: To estimate relative expanded uncertainty measurement of routine
      clinical chemistry analytes for international organisation for standardisation
      15189 accreditation. METHODS: This cross-sectional study was conducted at Dow
      International Medical College, Karachi, from September 2013 to May 2014. During
      the process of international organisation for standardisation 15189
      accreditation, measurement uncertainty was estimated for 13 clinical chemistry
      analytes using top-down approach. Relative combined uncertainty of each analyte
      was calculated by combining uncertainties of imprecision, bias and calibrators.
      Results of estimated imprecision, bias and expanded uncertainties were observed
      for allowable imprecision, bias and total analytical error for the respective
      analyte.. RESULTS: Uncertainties of imprecision were found within acceptable
      limits for all analytes except total protein (2.4% vs. 1.3%). Uncertainties of
      bias of all analytes were found within allowable limits. Relative expended
      uncertainties of all analytes were found acceptable except total protein (4.7%vs
      3.63%). CONCLUSIONS: The approach used to estimate the measurement uncertainty
      may be found simple and feasible by clinical laboratories interested in getting
      the relevant accreditation.

PMID- 28507356
TI  - School going adolescents' perception of family climate and mental problems:
      Results from Kocaeli, Turkey.
AB  - OBJECTIVE: To investigate the association between the perception of expressed
      emotion and psychopathology of school-going adolescents in a non-clinical sample.
      METHODS: The cross-sectional field study was conducted in Kocaeli, Turkey, and
      comprised high-school students during the 2014-15 school years. Data was
      collected using the Information Collection Form, Strengths and Difficulties
      Questionnaire and Shortened Level of Expressed Emotion Scale. SPSS 21 was used
      for data analysis. RESULTS: Of the 487 subjects, 295(60.57%) were girls and
      192(39.43%) were boys. The overall median age was 16 (inter-quartile range: 15-17
      years). There were significant positive relationships between the scales in terms
      of emotional problems (p<0.001), behavioural problems (p<0.001), Attention
      deficit/hyperactivity disorder (p<0.001), and peer relationship problems
      (p<0.001). There was also a negative significant relationship between pro-social
      behaviours and expressed emotion (p<0.001). CONCLUSIONS: The concept of perceived
      expressed emotion in non-clinical adolescents is useful in alarming clinicians
      and preventing mental disorders.

PMID- 28507357
TI  - Effect of skill laboratory training on academic performance of medical students.
AB  - OBJECTIVE: To observe the effect of skill lab training on academic performance of
      final year medical students in terms of marks obtained in long case, short case,
      objective structured clinical examination and viva. METHODS: The cross-sectional
      comparative study was conducted at Army Medical College, Rawalpindi from February
      to April 2015. Two batches of final year MBBS were recruited for the study. Batch
      1 received conventional training, and Batch 2 received skill lab training. The
      performance of students was assessed by comparing the marks obtained in long
      case, short case, objective structured clinical examination and viva. Data was
      analysed using SPSS 23. RESULTS: Of the 335 subjects, 168(50.1%) were male and
      167(49.9%) were female students with a mean age of 21.79+/-1.02 years. Batch 1
      had 151(45%) students and Batch 2 had 184(55%). Batch 2 got significantly higher
      marks in long case, short case and objective structured clinical examination
      (p<0.05 each). Viva result was not found to be related to training (p>0.05).
      CONCLUSIONS: Acquisition of clinical skills significantly improved when medial
      students were trained in skill laboratories.

PMID- 28507358
TI  - Effect of Citrullus colocynthis aqueous seed extract on beta cell regeneration
      and intra-islet vasculature in alloxan induced diabetic male albino rats.
AB  - OBJECTIVE: To observe the effect of Citrullus colocynthis on beta cell
      regeneration and intra-islet vasculature. METHODS: This experimental study was
      conducted at the University of Health Sciences, Lahore, Pakistan, from February
      2013 to January 2014. It comprised male wistar rats weighing 100-150gand aged 6-8
      weeks. The animals were divided into 6 groups. Group A1 served as control.
      Diabetes was induced in groups A2, B2 and C2 using single intravenous injection
      of 50mg/kg of alloxan. Animals having fasting blood glucose>250mg/dl were
      considered diabetic. Diabetic rats in groups B2 and C2 and their controls B1 and
      C1 were given 1ml/kg and 2ml/kg of Citrullus colocynthis aqueous seed extract
      orally per day for 14 days. Animals were sacrifised on day 15. RESULTS: Of the 48
      rats, there were 8(16.7%) in each group. Citrullus colocynthis has stabilized the
      body weight of rats and difference was statistically significant on days
      7(p<0.013) and 14(p<0.001). Citrullus colocynthis significantly reduced (p<0.001)
      the fasting blood sugar levels in a dose- and time-dependent manner. It increased
      the islet diameter (p<0.001) and beta cell count (p<0.001). The number of intra
      islet capillaries was increased in group C2, but the difference was not
      statistically significant (p>0.05). CONCLUSIONS: Citrullus colocynthis aqueous
      seed extract stabilised animal body weight and ameliorated hyperglycaemia in a
      dose- and time-dependent manner which was attributable to regenerative effect on
      beta cells and intra-islet vasculature.

PMID- 28507359
TI  - Under-representation of women in the editorial boards of medical and dental
      journals of Pakistan.
AB  - OBJECTIVE: To explore the representation of females in the field of medical
      journal editing in Pakistan. METHODS: This cross-sectional study was conducted
      from July 3 to 15, 2015 at Combined Military Hospital, Lahore. After exploring
      the website of Pakistan Medical and Dental Council, we surveyed the website of
      each journal and from their latest available edition discerned the editorial
      board's gender composition. Designations of female members were noted. Data was
      analysed using SPSS 20. RESULTS: A total of 2342 members served on the editorial
      boards of 79 journals of which 410(17.51%) were females. The maximum strength of
      women in a single journal was 23/30(76.6%). There were no women in the editorial
      boards of 11 (13.92%) journals. Among others, there were 188 (45.9%) Members of
      Editorial Board, 39 (9.5%) Editors, 39 (9.5%) Associate Editors, 34 (8.3 %)
      Members Advisory Board, 22 (5.4%) Subject Editors, 10 (2.4%) Editors-in-chief, 8
      (2.0%) Student Editors, 7 (1.7%) Statisticians, 3 (0.7%) Bibliographers, 2 (0.5%)
      Deputy Editors-in-chief, 1 (0.2%) Trainee Editor and 1(0.2%) epidemiologist.
      CONCLUSIONS: There was a low representation of women in the field of journal
      editing. A number of factors may be incriminated for this poor visibility.

PMID- 28507360
TI  - Psychometric properties of Conversion Disorder Scale- Revised (CDS) for children.
AB  - OBJECTIVE: To revise conversion disorder scale and to establish the psychometric
      properties of the revised scale. METHODS: This case-control study was conducted
      from February to June, 2014, at the Government College University, Lahore,
      Pakistan, and comprised schoolchildren and children with conversion disorder. In
      order to generate items for revised version of conversion disorder scale, seven
      practising mental health professionals were consulted. A list of 42 items was
      finalised for expert ratings. After empirical validation, a scale of 40 items was
      administered on the participants and factor analysis was conducted. RESULTS: Of
      the240 participants, 120(50%) were schoolchildren (controls group) and
      120(50%)were children with conversion disorder (clinical group).The results of
      factor analysis revealed five factors (swallowing and speech symptoms, motor
      symptoms, sensory symptoms, weakness and fatigue, and mixed symptoms) and
      retention of all 40 items of revised version of conversion disorder scale.
      Concurrent validity of the revised scale was found to be 0.81 which was
      significantly high. Similarly, discriminant validity of the scale was also high
      as both clinical and control groups had significant difference (p<0.001) in
      scores. Cronbach's alpha of scale was a=0.91 while item total correlation ranged
      from 0.50 to 0.80. The sensitivity and specificity analysis indicated that the
      revised conversion disorder scale was 76% sensitive to predicting conversion
      disorder while specificity showed that the scale was 73% accurate in specifying
      participants of the control group. CONCLUSIONS: The revised version of conversion
      disorder scale was a reliable and valid tool to be used for screening of children
      with conversion disorder.

PMID- 28507361
TI  - Self-related factors and decision making styles among early adults.
AB  - OBJECTIVE: To examine the effect of self-related factors, including self
      regulation, self-esteem and self-efficacy, on decision-making styles of early
      adults. METHODS: The cross-sectional study was conducted from February to August,
      2014 at four universities of Islamabad, Pakistan, and comprised adult students of
      both Social and Natural sciences. Data was collected through Self-Regulation
      Questionnaire, Self-Esteem Scale, Self-Efficacy Scale and the General Decision
      Making Styles Questionnaire. Data was subjected to multivariate regression
      analysis. RESULTS: Of the 300 participants, 160(53%) were men and 140(47%) were
      women. The overall mean age was 22.68+/-5.96 years. Besides, 170(56%) were
      studying Social sciences and 130(44%) Natural sciences. Self-regulation, self
      esteem and self-efficacy positively predicted rational and intuitive style and
      negatively predicted avoidant and spontaneous style. Self-efficacy and self
      regulation negatively predicted dependent style. CONCLUSIONS: Ensuring positive
      self-related factors affected adults' effective decision-making choices.

PMID- 28507362
TI  - Visual outcome of retinal vein occlusion in patients residing at high altitude.
AB  - OBJECTIVE: To study visual outcome in patients of high altitude retinopathy
      presenting with retinal venous occlusion. METHODS: The randomised clinical trial
      study was conducted at the Armed Forces Institute of Ophthalmology, Rawalpindi,
      Pakistan, from January 2013 to December 2015, and comprised eyes of lowlanders.
      Patients staying at high altitude (>8,000 feet above sea level) as part of their
      service duty and presented with retinal venous occlusive disease were included.
      Patients with history of diabetes, hypertension, glaucoma, any pre-existing
      retinal disease or age-related conditions responsible for decreased vision were
      excluded. Detailed ocular as well as systemic examination was carried out to
      establish the diagnosis of retinal venous occlusion. Patients were divided into
      two groups. First group was observed over a period of 6 months and labelled as
      control group, whereas the second group was treated with intravitrealbevacizumab
      and labelled as intervention group. Complete ocular examination was carried out
      in all patients at 4 weeks, 3 months and 6 months. SPSS 21 was used for data
      analysis. Results: A series of 32 eyes of 28 male patients were included. The
      overall mean age was 31.40+/-3.40 years. The mean altitude of their temporary
      stay was 4,120+/-941 metres above sea level and the mean duration of stay was
      6.80+/-4.13months. Besides, 21(75%) subjects were smokers. Moreover, 26(81.25%)
      eyes had central retinal vein occlusion while branch retinal vein occlusion was
      seen in 6(18.75%) eyes. The mean visual acuity in the control group was 0.70+/
      0.56 on Logarithm of the Minimum Angle of Resolution chart at the presentation
      while it was 0.26+/-0.87, 0.20+/-0.32 and 0.15+/-0.23 after 4 weeks, 3 months and
      6 months, respectively. The mean best corrected visual acuity in intervention
      group was 0.68 +/- 0.46 before treatment and 0.15+/-0.11, 0.12+/-0.11 and 0.10+/
      0.08 at 4 weeks, 3 months and 6 months, respectively. Significant post
      intervention change was observed in best corrected visual acuity at 6 months
      (p<0.05) in patients who presented with severe visual loss. CONCLUSIONS:
      Treatment with intravitrealbevacizumab may be considered in patients with severe
      visual loss at presentation.

PMID- 28507364
TI  - Evaluation of a communication skills training course for medical students using
      peer role-play.
AB  - OBJECTIVE: To evaluate the effect of using peer role-playing in learning the
      communication skills as a step in the development of the communication skills
      training course delivered to pre-clinical medical students. METHODS: This study
      was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, between
      September 2014 and February 2015 and comprised medical students. Mixed methods
      design was used to evaluate the developed communication skills training course.
      Tests were conducted before and after the communication skills training course to
      assess the students' self-reported communication. After the course, the students
      completed a satisfaction survey. Focus groups were conducted to assess the
      behavioural and organisational changes induced by the course. SPSS 16 was used
      for data analysis.. RESULTS: Of the293 respondents, 246(84%) were satisfied with
      the course. Overall, 169(58%) subjects chose the lectures as the most helpful
      methods for learning the communication skills while 124(42%) considered practical
      sessions as the most helpful method. Besides, 237(81%) respondents reported that
      the role-play was beneficial for their learning, while 219(75%) perceived the
      video-taped role-play as an appropriate method for assessing the communication
      skills. CONCLUSIONS: Peer role-play was found to be a feasible and well-perceived
      alternative method in facilitating the acquisition of communication skills..

PMID- 28507363
TI  - Status of cold chain in routine immunisation centres of the Expanded Programme on
      Immunisation in Quetta, Pakistan.
AB  - OBJECTIVE: To determine the status of cold chain and knowledge and practices of
      health workers about cold chain maintenance in routine immunisation health
      centres. METHODS: This cross-sectional study was conducted in Quetta, Pakistan,
      from May to July 2012, and comprised health facilities in the district. We
      interviewed the staff responsible for vaccine storage and cold chain maintenance
      and used a checklist to assess cold chain maintenance of routine expanded
      programme on immunisation vaccines. SPSS 16 was used for data analysis.. RESULTS:
      Of the 42 health facilities, staff of 13(30%) wrongly indicated that measles and
      Bacillus Calmette-Guerin were cold sensitive vaccines. Temperature of the ice
      lined refrigerators was not maintained twice daily in 18(43%) centres. There were
      no voltage stabilisers and standby power generators in 31(74%) and 38(90%)
      centres, respectively. Vaccine arrangement was found to be inappropriate in ice
      lined refrigerators of 38(90%) centres and ice packs were incorrectly used in
      carriers in 22(52%) centres. Vaccine stock was not charted in 39(93%) centres.
      Moreover, 4(10%) facilities did not have dedicated expanded programme on
      immunisation rooms whereas about 5(12%) and 33(79%) had no vaccinator and
      separate expanded programme on immunisation incharge appointed. Also, 32(76%)
      centres did not have a female vaccinator appointed. CONCLUSIONS: Although the
      majority of health staff had adequate knowledge, there were weaknesses in
      practice of maintaining the cold chain.

PMID- 28507365
TI  - Frequency and predictors of metabolic syndrome in adolescents /first year medical
      students of a public sector medical college Quetta, Pakistan.
AB  - Objective: To determine the prevalence of metabolic syndrome in medical students.
      METHODS: This cross-sectional study was conducted at the Bolan Medical College,
      Quetta, Pakistan, from August 2015 to January 2016, and comprised healthy first
      year medical students. Demographic data was assessed using a self-administered
      questionnaire. Height, weight and waist circumference were measured along with
      fasting blood sugar, high-density lipoprotein and triglycerides by using
      automated biochemistry analyser. SPSS 20 was used for data analysis. RESULTS: Of
      the 225 participants, 127(56.4%) were females. The overall mean age was 18.80+/
      0.426 years. Frequency of metabolic syndrome was 32(14.2%). Increased waist
      circumference, fasting blood sugar and triglycerides were associated with an
      increased likelihood of exhibiting metabolic syndrome (p<0,05 each). Male gender
      and high-density lipoprotein were found to be protective against metabolic
      syndrome (p<0.05 each).. CONCLUSIONS: The prevalence of metabolic syndrome is
      increasing in our adolescent population which demands screening from childhood
      and early adolescence..

PMID- 28507366
TI  - Over a decade of changing trends in surgical mortality; audit from a tertiary
      care hospital.
AB  - OBJECTIVE: A retrospective audit of the trend of mortality in the general surgery
      service at our hospital over the last decade was conducted to reflect the
      complexity of cases being seen. METHODS: Mortalities of 8 separate years, a
      decade apart, namely 1997, 1998, 1999, and 2000 as initial years (Group-I) and
      2011, 2012, 2013 and 2014 as recent years (Group-II) were reviewed. RESULTS:
      Total number of admissions in the service and surgeries performed during these
      two periods experienced an increase of 50.7% & 64.2 % respectively. The total
      mortalities showed an increase with 139 (mortality rate 0.96%) seen in Group I to
      285 (mortality rate 1.31%) seen in Group II a percentage increase of 105%.
      Comparing the operative mortality, separately, mortality rate dropped from 1.21%
      to 1.16% of all surgeries. Analyzing non-operative mortality showed a significant
      increase from six deaths in Group-I comprising 4.3% to 76 non-operative deaths in
      Group-II corresponding to 26.7% (p=0.000). Deaths due to Trauma increased from
      12.9% to 25.3%, p=0.04, a reversed trend was seen in deaths due to GI Bleeding
      11.5% to 3.2%, p=0.001. Significantly more patients in Group-II had higher ASA
      levels as compared to Group-I (62% vs. 46%, p<0.005). CONCLUSIONS: This study
      shows an increase in total mortality rate over the years, change was mainly due
      to an increase in non-operative mortality. Trauma became the predominant cause of
      death.

PMID- 28507367
TI  - Management of cervical trauma: A Brief review.
AB  - Cervical injury is not uncommon in any trauma, especially in road traffic
      accident. A standard approach, towards, transport, workup, and management is
      required for best outcomes, and decrease morbidity. We tried to review the recent
      literature and briefly discuss the management protocols concluded that in our
      setting, emergency ambulance personnel and Emergency Room doctors should be
      trained in dealing with all kinds of cervical spine trauma, they should be aware
      of recent guidelines and should refrain from using steroids routinely. By
      following guidelines, large numbers of cervical spine injury patients can
      benefit.

PMID- 28507368
TI  - The confounding factors leading to plagiarism in academic writing and some
      suggested remedies: A systematic review.
AB  - There is a staggering upsurge in the incidence of plagiarism of scientific
      literature. Literature shows divergent views about the factors that make
      plagiarism reprehensible. This review explores the causes and remedies for the
      perennial academic problem of plagiarism. Data sources were searched for full
      text English language articles published from 2000 to 2015. Data selection was
      done using medical subject headline (MeSH) terms plagiarism, unethical writing,
      academic theft, retraction, medical field, and plagiarism detection software.
      Data extraction was undertaken by selecting titles from retrieved references and
      data synthesis identified key factors leading to plagiarism such as unawareness
      of research ethics, poor writing skills and pressure or publish mantra.
      Plagiarism can be managed by a balance among its prevention, detection by
      plagiarism detection software, and institutional sanctions against proven
      plagiarists. Educating researchers about ethical principles of academic writing
      and institutional support in training writers about academic integrity and
      ethical publications can curtail plagiarism.

PMID- 28507369
TI  - Nature, scope and use of economic evaluation of healthcare programmes: with
      special reference to Pakistan.
AB  - Economic evaluation (EE)/cost effectiveness analysis(CEA) of healthcare
      programmes is an emerging area, yet the resource base to apprehend EE/CEA is very
      limited in Pakistan. This paper attempts to fill this gap by providing a basic
      text in the field of EE with special reference to Pakistan. We used four
      dimensional criteria (available, relevant, complete and accurate) for reviewing
      the EE contents in the locally available textbooks and reading material on public
      health. We find CEA as core competency and skill of medical doctors in
      undergraduate medical curricula yet we could not find EE contents in the
      recommended textbooks. We find that economic evaluation entails two rules: both
      cost and effectiveness should be included in the analysis, and there must be a
      comparison of at least two drugs or medical intervention. We describe EE/CEA in
      this article and recommend that EE content should be included in the medical and
      public health curriculum in Pakistan.

PMID- 28507370
TI  - A comparative study of dynamic soft tissue mobilization vs. passive stretching
      technique to improve the flexibility of hamstrings in cricket players.
AB  - Different therapies are available for correcting the tightness of hamstring
      muscles. Objective of this study was to compare the effectiveness of Dynamic Soft
      Tissue Mobilization DSTM technique and Passive Stretching PS to improve the
      flexibility of tight hamstrings in cricket players. A total of 120 cricket
      players having tightness of hamstrings were enrolled and randomized into two
      groups A and B using lottery method. Group-A was treated with DSTM and group-B
      with PS to improve the flexibility of hamstrings. Active Knee Extension Angle
      AKEA test was used to measure the hamstring tightness as it is a gold standard
      test for this purpose. The mean value of AKEA, pre-treatment score deficient to
      180 degrees for DSTM was 25.66 +/- 6.90, and that of PS was 25.46 +/- 6.89, while
      the post-treatment score was 10.81 +/- 4.30, and 18.63 +/- 7.06 respectively.
      Post-treatment score for DSTM was statistically lower than PS. (p-value < 0.05).
      So it was concluded that it is better to use DSTM for acquiring better results.

PMID- 28507371
TI  - Intellectual wellness in medical university teachers: Gender based comparison.
AB  - A cross section, questionnaire based study was carried out from January 2012 till
      December 2014 to compare intellectual wellness (IW) awareness on the basis of
      gender in teachers of basic sciences at medical universities of Karachi,
      Pakistan. Data was collected from 3 public and 5 private medical universities of
      Karachi, Pakistan. Questionnaire was tailored from "Wellness Wheel" and responses
      were aggregated for eight questions in the dimension of IW to obtain aggregate IW
      score. Reliability of the questionnaire was measured using Cronbach's alpha. The
      average intellectual score was 24.99 +/- 3.93 with a minimum score of 8 and
      maximum 32.The frequency of keeping informed about research updates was
      significantly higher in males (p = 0.043) that emphasized significantly better IW
      awareness of male medical teachers involved in teaching of medical sciences in
      both public and private medical universities of Pakistan.

PMID- 28507372
TI  - Medicinal role of papaya seeds on thrombocyte count tested on healthy rabbits.
AB  - The main objective of the current study is to evaluate the medicinal role of
      Papaya seeds on thrombocyte count and hepatic parameter on healthy rabbits.
      Experimental and Interventional study, at the Department of pharmacology Baqai
      Medical University Karachi. Rabbits (18 in number different age and both sex)
      were included, subsequently subdivided into three group (n=6). Group A (Control),
      B and C (sample fed dose 250 & 500mg OD, oral route). Blood were drawn 0 time,
      subsequently samples were drawn at 15, 30, 45 days. Data was analyzed by using
      SPSS 19.0. Analysis of results showed increase in the Platelet level 19.2%,
      65.5%. No significant change seen in the SGPT, Alkaline Phosphatase, WBC,
      Neutrophil, Lymphocytes, Eosinophils and Monocytes as compared with the controls.
      It can be concluded that the administration of Papaya seeds powder dose rapidly
      increase platelet count and may play an important therapeutic role in
      thrombocytopenia.

PMID- 28507373
TI  - Comparison of low level laser therapy and interferential current on post stroke
      shoulder pain.
AB  - The objective of the study was to compare the effects of LASER therapy and
      Interferential current on post stroke shoulder pain. Diagnosed patients (n=38) of
      post stroke shoulder pain were randomly divided into two groups i.e., LASER group
      (LG =20 patients) and Interferential current group (IFCG=18 patients). The
      variables under study were pain, satisfaction, disability, and function level
      before and after treatment. Improvement in pain and satisfaction level after
      LASER therapy was significant (p<0.001). However improvement in functional level
      was not significant (p> 0.05). The study findings revealed that LASER therapy is
      more effective than Interferential current in decreasing pain and increasing
      satisfaction level of stroke patients having shoulder pain.

PMID- 28507375
TI  - Twin abdominal pregnancy - A rare scenario.
AB  - Twin abdominal pregnancy is rarely encountered by gynaecologists throughout their
      professional career. It poses a challenge in terms of diagnosis and management.
      This case report is about a patient who was diagnosed and successfully managed
      for this complication at a peripheral hospital of Pakistan Armed Forces.

PMID- 28507374
TI  - Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous
      albinism through whole exome sequencing.
AB  - Oculocutaneous albinism (OCA) is a disorder of defective melanin biosynthesis
      that is characterized by hypo-pigmentation of skin, hair and retinal pigment
      epithelium. Phenotypically, OCA patients exhibit white milky skin, whitish to
      golden hair and deterioration of retinal cells. Until recently, genetic studies
      have reported seven causative genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11
      and MCIR) and an uncharacterized OCA5 locus. Herein we present the medico-genetic
      study of three Pakistani patients inheriting autosomal recessive OCA. Whole exome
      sequencing, followed by Sanger DNA sequencing for segregation analysis, revealed
      recurrent mutations c.346C>T (p.Arg116*) and c.1255G>A (p.Gly419Arg) (family A
      and B respectively) in TYR gene, while the patient from family C did not reveal
      any known gene mutation, which suggests the involvement of some novel genetic
      factor. It is the first report of mapping c.346C>T mutation in a Pakistani
      patient. Our study further extends the evidence of genetic hotspots regions in
      TYR gene causing OCA in Pakistani population.

PMID- 28507376
TI  - Extraoral approach of the surgical treatment of sublingual epidermoid cyst: A
      case report.
AB  - Epidermoid and dermoid cysts account for <0.01% of all oral cavity lesions with
      dermoid cyst which is twice as common to epidermoid. Epidermoid cysts are benign
      lesions that occur rarely in children. They usually present early in life as an
      asymptomatic mass. The treatment option is surgical and intraoral or extraoral
      approaches can be performed according to the localization and size of the mass.
      This report presents an 11 year old child with a sublingual epidermoid cyst
      treated extraorally.

PMID- 28507377
TI  - Spontaneous evisceration of umbilical hernia in a patient with congenital
      nephrotic syndrome.
AB  - Congenital nephrotic syndrome is a term used to describe a condition in babies
      who develop severe proteinuria and hypoalbuminaemia within their first three
      months of life. They generally have oedema and ascites from birth which, because
      of increased intra-abdominal pressure, can result in an umbilical hernia. The
      report presents a five-month old infant with congenital nephrotic syndrome who
      had spontaneous umbilical hernia rupture with evisceration. The approach to
      umbilical hernias is usually conservative, but in selected cases elective surgery
      may be indicated.

PMID- 28507378
TI  - Case series of rare Interstitial Lung Disease (ILD).
AB  - Pulmonary alveolar proteinosis (PAP) is a rare lung disease where periodic acid
      Schiff (PAS)-positive eosinophilic material accumulates in the alveoli of the
      lungs. Here we describe two cases of young males who presented with dynpnoea and
      weight loss. The HRCT scan of the chest in both cases showed the typical "crazy
      paving" pattern and lung biopsies confirmed the diagnosis of PAP. They showed
      remarkable symptomatic improvement with therapeutic whole lung lavage.

PMID- 28507379
TI  - Accuracy of frozen sections in oral cancer resections, an experience of a
      tertiary care hospital.
AB  - The aim our study was to determine the accuracy of frozen sections in oral cancer
      resections. Patients who underwent oral cancer resection at Patel Hospital were
      included in the study. Tissues for frozen sections were obtained from the mucosal
      margins and tumour bed. Frozen sections were compared with the paraffin embedded
      sections which served as the gold standard in our study. Sensitivity,
      specificity, positive predictive value, negative predictive value, accuracy and
      kappa statistics were calculated. A total of 299 frozen sections were obtained
      from 77 patients who underwent oral cancer resection, mean (3.88+/-0.76). Frozen
      sections' sensitivity in relation to permanent sections was 72.7% and specificity
      of 93.9%. The overall accuracy of the test was 90.9%. Kappa value was calculated
      to be 0.642, which showed a moderate agreement. Frozen sections are accurate
      enough to be used in assessing intraoperative margin assessment for tumour
      clearance.

PMID- 28507380
TI  - Malaria and diabetes.
AB  - Both malaria and diabetes are more common in the developing world, and are major
      public health challenges. A direct relationship between these 2 conditions has
      not been evaluated. This review article assessed the literature guaging the
      relationship between these two conditions, and suggests a pragmatic approach to
      management. References for this review were identified through searches of
      PubMed, Medline, and Embase for articles published to October 2016 using the
      terms "diabetes" [MeSH Terms] AND "malaria" [All Fields]. The reference lists of
      the articles thus identified were also searched. The search was not restricted to
      English-language literature. Malaria has been documented to be more common in
      diabetes, in several studies from Africa. Malarial infection during pregnancy is
      an important cause of low birth weight and anaemia, and may contribute to the
      intra-uterine hypothesis explanation for the diabetes epidemic. Prevention and
      timely/effective management of malaria during pregnancy may therefore be viewed
      as a primordial preventive strategy against diabetes. Patients with diabetes have
      atypical malaria presentations. Glucose-6-phosphate dehydrogenase deficiency,
      which is associated with primaquine failure for radical cure is also associated
      with dysglycaemia. Type 2 Diabetic mice infected with malaria are more efficient
      at infecting mosquitoes. A similar synergy in humans warrants evaluation, which
      would then make "diabetic malaria" a public health problem. Metformin has well
      known anti-malarial properties. There is significant literature available
      highlighting the link between diabetes and malaria, an area warranting active
      further research. Metformin as a prophylactic agent for malaria prevention
      warrants evaluation.

PMID- 28507381
TI  - Sleep hygiene and diabetes: Suggestions for primary care.
AB  - Sleep problems are common in chronic disorders like diabetes and are the result
      of poor diet and unhealthy lifestyles. Comprehensive management of diabetes
      entails lifestyle management and restoration of good habits. Sleep hygiene
      maintenance helps persons living with diabetes enjoy a better quality of life by
      restoring normal sleep patterns and thereby improving glycaemic control.

PMID- 28507382
TI  - Prognostic significance of IDH 1 mutation in patients with glioblastoma
      multiforme.
AB  - Focus of brain tumour research is shifting towards tumour genesis and genetics,
      and possible development of individualized treatment plans. Genetic analysis
      shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most
      Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic
      significance of IDH 1 mutation on the basis of published evidence. Multiple
      retrospective clinical analyses correlate the presence of IDH1 mutation in GBM
      with good prognostic outcomes compared to wild-type IDH1. A systematic review
      reported similar results. Based on the review of current literature IDH1 mutation
      is an independent factor for longer overall survival (OS) and progression free
      survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic
      significance opens up new avenues for treatment.

PMID- 28507383
TI  - Short-term antibacterial efficacy of a new silver nanoparticle-containing
      toothbrush.

PMID- 28507384
TI  - Intraosseous access over central venous or peripheral venous line as an initial
      means of resuscitation- A possible measure for improving outcomes of cardiac
      arrests.

PMID- 28507385
TI  - Higher education needs more improvement: The case of Pakistan.

PMID- 28507386
TI  - Publish or perish: A sign of caution for authors to avoid predatory journals.

PMID- 28507387
TI  - Multidisciplinary approach to the prenatal diagnosis and Post natal management of
      a large suprasellar arachnoid cyst: A case report.
AB  - Arachnoid cysts are intra-arachnoid sacs filled with cerebrospinal fluid
      representing a rare occurence in neonates. We report the case of a suprasellar
      arachnoid cyst diagnosed prenatally at 21 weeks gestation on routine obstetric
      ultrasound. A cystic lesion was picked up incidentally at routine antenatal scan.
      The cyst was noted to be increasing in size over a series of radiological scans.
      The cyst was diagnosed as a suprasellar arachnoid cyst compressing the third
      ventricle and bilateral lateral ventricles. A left pteryonal craniotomy for
      cystocisternostomy of large suprasellar cyst was performed initially. Within a
      month the cyst recurred with clinical and radiological evidence. An Endoscopic
      Third Ventriculostomy (ETV) with fenestration was performed.The patient was
      shifted to the NICU and discharged after 3 days in a stable condition. Patient
      was followed after 1 week and reassured and advised for one year follow-up.

PMID- 28507389
TI  - Bouncing back across the board: Results of the 2016 CVMA Practice Owners Economic
      Survey.

PMID- 28507388
TI  - Congenital nuclear cataracts in a Holstein dairy herd.
AB  - This report describes congenital nuclear cataracts and posterior lenticonus in a
      closed purebred Holstein dairy herd in Canada. Ophthalmic examinations were
      completed on 30 male and 249 female cattle aged newborn to 10 years old.
      Nutritional, infectious, and toxic etiologies were investigated. Necropsies of 3
      affected calves were performed and eyes of 2 additional affected calves were
      examined with light microscopy. Bilateral nuclear cataracts were identified in
      53/279 (19%) animals. Additional congenital anomalies observed included posterior
      lenticonus, iris to lens persistent pupillary membranes (n = 7), and lenticular
      colobomata (n = 1). Heifers did not give birth to calves with congenital nuclear
      cataracts (0/105), whereas the incidence of affected calves born to multiparous
      cows was 31% (53/171). The animals with nuclear cataracts ranged from newborn to
      8 years old. The cataracts appeared to be non- or minimally progressive. Light
      microscopic examination of 10 affected globes confirmed nuclear cataract with
      posterior lenticonus (n = 10). Pedigree analysis was inconclusive. Polymerase
      chain reaction and sequence analysis for the NID1 gene deletion were negative.
      The etiology of the congenital lenticular anomalies was not determined.

PMID- 28507390
TI  - High-quality PVD graphene growth by fullerene decomposition on Cu foils.
AB  - We present a new protocol to grow large-area, high-quality single-layer graphene
      on Cu foils at relatively low temperatures. We use C60 molecules evaporated in
      ultra high vacuum conditions as carbon source. This clean environment results in
      a strong reduction of oxygen-containing groups as depicted by X-ray photoelectron
      spectroscopy (XPS). Unzipping of C60 is thermally promoted by annealing the
      substrate at 800oC during evaporation. The graphene layer extends over areas
      larger than the Cu crystallite size, although it is changing its orientation with
      respect to the surface in the wrinkles and grain boundaries, producing a
      modulated ring in the low energy electron diffraction (LEED) pattern. This
      protocol is a self-limiting process leading exclusively to one single graphene
      layer. Raman spectroscopy confirms the high quality of the grown graphene. This
      layer exhibits an unperturbed Dirac-cone with a clear n-doping of 0.77 eV, which
      is caused by the interaction between graphene and substrate. Density functional
      theory (DFT) calculations show that this interaction can be induced by a coupling
      between graphene and substrate at specific points of the structure leading to a
      local sp3 configuration, which also contribute to the D-band in the Raman
      spectra.

PMID- 28507391
TI  - Electrical Characterization of Glycerin: Water Mixtures: Implications for Use as
      a Coupling Medium in Microwave Tomography.
AB  - We examine the broadband behavior of complex electrical properties of glycerin
      and water mixtures over the frequency range of 0.1 - 25.0 GHz, especially as they
      relate to using these liquids as coupling media for microwave tomographic
      imaging. Their combination is unique in that they are mutually miscible over the
      full range of concentrations which allows them to be tailored to dielectric
      property matching for biological tissues. While the resultant mixture properties
      are partially driven by differences in the inherent low frequency permittivity of
      each constituent, relaxation frequency shifts play a disproportionately larger
      role in increasing the permittivity dispersion while also dramatically increasing
      the effective conductivity over the frequency range of 1 to 3 GHz. For the full
      range of mixture ratios, the relaxation frequency shifts from 17.5 GHz for 0%
      glycerin to less than 0.1 GHz for 100% glycerin. Of particular interest is the
      fact that the conductivity stays above 1.0 S/m over the 1-3 GHz range for
      glycerin mixture ratios (70-90% glycerin) we use for microwave breast tomography.
      The high level of attenuation is critical for suppressing unwanted multipath
      signals. This paper presents a full characterization of these liquids along with
      a discussion of their benefits and limitations in the context of microwave
      tomography.

PMID- 28507392
TI  - Consumer medicine information.

PMID- 28507393
TI  - Treating patients on new anticoagulant drugs.

PMID- 28507394
TI  - Treating dental patients on new anticoagulant drugs.

PMID- 28507395
TI  - Correcting iron deficiency.

PMID- 28507396
TI  - Oral supplements and iron deficiency.

PMID- 28507397
TI  - Managing the drug treatment of rheumatoid arthritis.

PMID- 28507398
TI  - Managing acute pulmonary oedema.

PMID- 28507399
TI  - Managing hepatitis C in general practice.

PMID- 28507401
TI  - Economic evaluation of medicines.

PMID- 28507400
TI  - Prescribing for people with acute rheumatic fever.

PMID- 28507402
TI  - Proton pump inhibitor-associated hypomagnesaemia and hypocalcaemia.

PMID- 28507403
TI  - App Review: Drug names.

PMID- 28507404
TI  - Ceritinib for non-small cell lung cancer.

PMID- 28507405
TI  - Erratum: Long-term prescribing of new oral anticoagulants.
AB  - [This corrects the article on p. 200 in vol. 39, PMID: 27990047.].

PMID- 28507406
TI  - Evaluation of different agroindustrial waste on the effect of different carcass
      characteristics and physiological and biochemical parameters in broilers chicken.
AB  - AIM: This study was conducted to evaluate the physiological and biochemical
      effect in chickens of the Ross breed of a food enriched with agroindustrial
      waste. MATERIALS AND METHODS: The food is one of the main components of the total
      cost for the production of chickens. Rations should be formulated to provide the
      correct balance of energy, protein, amino acids, minerals, vitamins and essential
      fatty acids, to allow optimal growth and performance. This study was intended to
      evaluate a natural feed for chicken, made from corn, yucca meal, eggshells,
      orange peel, soybean meal, salt and garlic, enriched with agroindustrial waste
      (molasses, milk whey and ferment of coffee). The weight gain was evaluated in
      broilers using a diet enriched with different agroindustrial wastes, with respect
      to a control food of the same composition but not containing residue. To develop
      the experiment 120 male Ross 308 chicks were used, these were evaluated for 6
      weeks. Physicochemical test for the food and the agroindustrial waste were
      performed; moisture was determined; organic carbon, organic material and the ash,
      to characterize the agroindustrial wastes, the reducing sugars content using a
      spectrophotometer at 540 nm and proteins through the Kjeldahl method was
      evaluated. During the experiment, the weight gain of chickens and feed conversion
      was evaluated; the end of the experiment the weight of eviscerated channel
      relative weight breast, thighs, pancreas, and abdominal fat was determined,
      besides including blood chemistries as determination of cholesterol,
      triglycerides, and glucose. Finally, the microbiological analyzes to detect the
      presence of Escherichia coli in the cecum was determinate. Data were analyzed by
      InfoStat statistical program using the generalized linear model procedure. The
      statistical comparison was made by Tukey test at the 95% probability level.
      RESULTS: After the evaluation, fed chickens with the treatments food + milk whey
      (FMW) and food + ferment of coffee (FFC) demonstrated increased from 1949 to 1892
      g, respectively, to the 42 days of evaluation, showing the best treatment for
      weight gain. However, the FFC treatment showed the best feed conversion reaching
      values of 1.79 related to levels of blood glucose (249 mg/dl). Even so the
      eviscerated channel yields were higher for the treatment FFC reaching 1810.1 g
      unlike the treatment FMW which it reached a weight of 1718.2 g with increased
      formation of abdominal fat (7.4 g) unlike other treatments. From the results, it
      is concluded that food enriched with coffee ferment allows an increase in weight,
      better feed conversion in addition to high production of lean meat. CONCLUSION:
      It was shown that the best treatment was the food enriched with the ferment of
      coffee, due to increased intake and weight gain at the end of 42 days of the
      experiment.

PMID- 28507407
TI  - Study on postpartum estrus of guinea pigs (Cavia cobaya) using Anredera
      cordifolia leaf extract.
AB  - AIM: The purpose of this study was to determine the postpartum estrus cycle of
      guinea pigs (Cavia cobaya) using Anredera cordifolia leaf extract. MATERIALS AND
      METHODS: Materials used were 8 males and 8 females of C. cobaya with body weight
      ranged 400-450 g. Mating ratio applied was 1:1. Treatments given were 0, 10, 50
      and 90 mg of A. cordifolia leaf extract/head, designated as T0, T1, T2 and T3,
      respectively. Two females were subjected for each treatment. A. cordifolia leaf
      extract was administered orally from 10 days prepartum to 10 days postpartum.
      Observation of mating behavior, vulva morphology, and vaginal smear preparation
      was done in the afternoon for 10 days subsequence postpartum. Data were analyzed
      by univariate method and descriptively. RESULTS: The results showed that the
      addition of A. cordifolia leaf extract 50 mg orally could accelerate the time of
      postpartum estrus based on the average frequency of mating behavior consisting of
      behavioral approach, allow the buck to sniffing her, mating positions, standing
      heat, lordosis position, and copulation. During estrus, vulva morphology was red
      color, had much mucus and no thin membrane covering vagina. There were a lot of
      superficial cells on vagina. CONCLUSION: The best treatment to accelerate
      occurring postpartum estrus was the addition of A. cordifolia leaf extract as
      many as 50 mg/head weight (T2) orally.

PMID- 28507408
TI  - Effect of dietary supplementation of fermented fish silage on serum biochemical
      parameters of broiler Japanese quails (Coturnix coturnix japonica).
AB  - AIM: The objective of this study was to evaluate the effect of feeding fermented
      fish silage (FFS) on serum biochemical parameters of Japanese quails (Coturnix
      coturnix japonica). MATERIALS AND METHODS: A total of 192, 7-day-old broiler
      Japanese quail chicks of either sex, were randomly distributed into four dietary
      treatments with four replicates in each group having 12 chicks in each replicate
      pen. The dietary treatments were T1 - Control diet, T2 - Diet containing 5% FFS,
      T3 - Diet containing 10% FFS, and T4 - Diet containing 15% FFS. Group body weight
      and feed consumption were recorded at weekly intervals. Feed conversion ratio
      (FCR) was derived by dividing the feed consumed with the weekly body weight gain.
      At the end of the experiment, 8 birds from each treatment were selected randomly
      and sacrificed by cervical dislocation to study the carcass traits expressed as %
      pre-slaughter live weight. At 5 weeks of age, about 2 ml of blood was taken from
      the jugular vein of each selected bird, and serum samples were separated after
      centrifugation. Total protein, albumin/globulin (A/G) ratio, calcium, phosphorus,
      triglyceride, total cholesterol, high density lipoprotein-cholesterol (HDL-C),
      very low density lipoprotein-cholesterol (VLDL-C), low density lipoprotein
      cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate
      aminotransferase (AST) were estimated in the serum. RESULT: The cumulative body
      weight gains from 1 to 5 weeks of age did not vary significantly between control
      and 5% FFS group. However, a linear decrease in body weight gain was observed by
      increasing the levels of FFS beyond 5% in the diet. The cumulative feed
      consumption was significantly higher in case of birds under control group during
      1-5 weeks of age as compared to birds fed FFS based diet (5%, 10%, and 15%). No
      statistical difference in cumulative feed conversion ratio could be noticed
      during 1-5 weeks of age. The eviscerated yield decreased and giblet weight
      increased due to the dietary supplementation of FFS at 15% level. The breast meat
      yield decreased due to dietary supplementation of FFS at 10% and 15% level in the
      diet of broiler Japanese quails. The effect of FFS was found to be nonsignificant
      (p>0.05) with respect to serum total protein, globulin and A/G ratio under
      different treatments whereas significant difference observed in serum albumin
      concentration. Dietary supplementation of FFS at 10% and 15% level significantly
      increased the AST concentration in serum. There was no significant difference
      among the treatments regarding the parameters such as ALT, calcium, phosphorous,
      triglyceride, total cholesterol, HDL-C, VLDL-C, and LDL-C. CONCLUSION: The serum
      biochemical parameters are influenced by the dietary supplementation of FFS in
      broiler Japanese quails.

PMID- 28507409
TI  - Toxoplasma gondii Type I, predominant genotype isolated from sheep in South of
      Iran.
AB  - AIM: This study was performed to determine the genetic diversity of Toxoplasma
      gondii in sheep using nested-polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) in Southern Iran. MATERIALS AND METHODS: The
      tissue samples of diaphragm and heart from 125 sheep were collected from the main
      slaughterhouses of Jahrom district in South of Fars province, Iran, between
      Aprils and June 2013. The DNA were extracted and analyzed by nested-PCR using
      specific primers for SAG2 and GRA6 loci. RFLP was used to classify strains into
      one of the three major lineages of T. gondii. RESULTS: T. gondii Type I was
      predominant in this area. The data obtained from both loci demonstrated that the
      frequency of each genotype was 72% Type I, 2.4% Type III, 7.2% mixed Type I and
      II, 16.8% mixed Type I and III, 0.8% mixed Type II and III, and 0.8% mixed Type
      I, II and III. CONCLUSIONS: Although the previously published data indicated that
      Type II is the predominant T. gondii genotype in sheep in the other parts of the
      world, this study showed that genotype I is the dominant genotype of T. gondii in
      the southern Iran; however, other genotypes were detected. High diversity of T.
      gondii genotypes including mix genotypes in lambs is of importance for the public
      health. These studies depict a new mapping of T. gondii genotypes pattern which
      could be very helpful in toxoplasmosis control and prevention.

PMID- 28507410
TI  - Isolation and identification of fungi associated with spoilt fruits vended in
      Gwagwalada market, Abuja, Nigeria.
AB  - AIM: Annual reports have shown that 20% of fruits and vegetables produced are
      lost to spoilage. This study was undertaken to isolate and identify fungi that
      are associated with spoilt fruits commonly sold in Gwagwalada market, Abuja, and
      recommend appropriate control measure. MATERIALS AND METHODS: The study was
      conducted in Gwagwalada metropolis, Gwagwalada Area Council of the Federal
      Capital Territory, Abuja, Nigeria. A total of 100 spoilt fruits which include
      pawpaw (Carica papaya), orange (Citrus sinensis), tomato (Lycopersicon
      esculentum), pineapple (Ananas comosus), and watermelon (Citrullus vulgaris) were
      purchased and examined for the presence of fungal organisms using standard
      methods. The data collected were analyzed using simple descriptive statistics
      (frequency and mean) and analysis of variance (p<0.05). RESULTS: Aspergillus
      niger had the highest occurrence in pineapple, watermelon, oranges, pawpaw, and
      tomatoes with a frequency of 38%. Fusarium avenaceum followed with the frequency
      of occurrence of 31% in fruits such as pineapple, watermelon, oranges, pawpaw,
      and tomatoes while Penicillium digitatum and Rhizopus stolonifer had the least
      frequency of 4% each in tomato; and orange and tomato, respectively. Other fungal
      species were identified as yeast (Saccharomyces species) (10%), Fusarium solani
      (8%), and Aspergillus flavus (5%). The highest prevalence rate was 70% of A.
      niger from orange followed by F. avenaceum of which 65% isolates were recovered
      from pawpaw. Other fungal organisms such as yeast (Saccharomyces species), P.
      digitatum and R. stolonifer were isolated with varying prevalence (40%, 20%, and
      5%) from watermelon, tomato, and orange, respectively. However, there was no
      significant difference in the fungal load of the various fruits studied (analysis
      of variance=478.2857, p<0.05, F=4.680067 and df=34). CONCLUSION: The pathogenic
      fungi species associated with fruits spoilage in this study are of economical and
      public health significance. A. niger causes black mold in certain fruits and
      vegetables. Some strains of A. niger have been reported to produce potent
      mycotoxins called ochratoxins that can be harmful to human beings and animals.
      Care should be taken during handling of these fruits and improved technology
      based preservation methods are suggested to enhance the keeping quality of
      fruits.

PMID- 28507411
TI  - Cross-sectional study on bovine mastitis and its associated risk factors in Ambo
      district of West Shewa zone, Oromia, Ethiopia.
AB  - AIM: A cross-sectional study was conducted to estimate the prevalence and
      associated risk factors of mastitis in dairy cows. MATERIALS AND METHODS: A total
      of 302 dairy cows were selected from all volunteer dairy farms in Ambo district
      of West Shewa Zone, Oromia region. Thorough clinical examination was made on all
      lactating cows for evidence of signs of clinical mastitis followed by collection
      of milk sample for examination of gross changes of milk secretion and California
      mastitis test. RESULT: About 126 (41.7%) cows had mastitis, of which 9.9%
      (30/302) were clinical and 32.8% (96/302) were subclinical mastitis cases. The
      quarter level prevalence was 44.4% (536/1208), comprising 9.3% (112/1208),
      clinical and 32.8% (396/1208) subclinical forms of mastitis. In addition, 5.5%
      (66/1208) of teats were found to be blind on the clinical examination of udder
      and teat. The Chi-square analysis of intrinsic risk factors revealed
      significantly (p<0.05) higher prevalence of mastitis in crossbred cattle (47.2%)
      than indigenous (15.4%), in cattle above 7 years (75%) than less than 2-6 years
      of age (28%) and cows given more than 4 calves (81.3%) than those with less than
      4 calves (31.1%) irrespective to their lactation stage. There was also
      significantly (p<0.05) higher mastitis prevalence in larger (46.6%) than smaller
      herds (24.2%) and among the farming systems in semi-intensive (47.1%) and
      intensive (42.3%) than extensive (8.1%) management system. CONCLUSION: This study
      indicated a higher prevalence of mastitis linked with several risk factors. Thus,
      early diagnosis and regular screening of cows for subclinical mastitis together
      with proper therapeutic management of clinical cases are of paramount importance.
      Moreover, control and prevention strategies should be designed and implemented
      with great emphasis given to risk factors to reduce bovine mastitis and its
      impact on milk production and food security.

PMID- 28507412
TI  - The effects of quercetin on microRNA and inflammatory gene expression in
      lipopolysaccharide-stimulated bovine neutrophils.
AB  - AIM: To investigate gene expression of microRNA (miRNA) milieus (MIRLET7E, MIR17,
      MIR24-2, MIR146A, and MIR181C), inflammatory cytokine genes (interleukin 1beta
      [IL1B], IL6, CXCL8, and tumor necrosis factor [TNF]), and the pathogen receptor
      toll-like receptor (TLR4) in bovine neutrophils under quercetin supplementation.
      MATERIALS AND METHODS: Isolated bovine neutrophils were incubated with bacterial
      lipopolysaccharide under quercetin treatment or left untreated. Real-time
      polymerase chain reaction was performed to determine the expression of the miRNAs
      and messenger RNA (mRNA) transcripts in neutrophils. RESULTS: Quercetin-treated
      neutrophils exhibited a remarkable suppression in MIR24-2, MIR146A, and MIR181C
      expression. Similarly, mRNA expression of IL1B, IL6, CXCL8, TLR4, and TNF genes
      noticeably declined in the quercetin group. Many proinflammatory genes (IL1B,
      IL6, and CXCL8) and the pathogen receptor TLR4 had a negative correlation with
      MIR146A and MIR181C as revealed by Pearson correlation. CONCLUSIONS: Interaction
      between cognate mRNAs and miRNAs under quercetin supplementation can be
      summarized as a positive or negative correlation. This finding may help
      understand the effects of quercetin either on miRNA or gene expression during
      inflammation, especially as a potentially applicable indicator in bovine
      mastitis.

PMID- 28507413
TI  - Prevalence of echinococcosis and Taenia hydatigena cysticercosis in slaughtered
      small ruminants at the livestock-wildlife interface areas of Ngorongoro,
      Tanzania.
AB  - AIM: Echinococcosis or hydatidosis (due to the larval stage of Echinococcus spp.)
      and cysticercosis (due to the larval stage of Taenia hydatigena) pose a
      significant economic losses due to slaughter condemnation and risk to public
      health in developing countries such as Tanzania where sanitation is poor and
      people live in close proximity with each other and with animals. This study was
      conducted to determine the prevalence of and to identify the predisposing factors
      for echinococcosis and cysticercosis in sheep and goats at three slaughter slabs
      located in the livestock-wildlife interface areas of Ngorongoro, Tanzania.
      MATERIALS AND METHODS: A cross-sectional based survey was conducted, from January
      2013 to April 2013, whereby a total of 180 animals comprising 90 goats and 90
      sheep of both sexes were examined at postmortem for the evidence of larval stages
      of Echinococcus spp. (hydatid cyst) and T. hydatigena (Cysticercus tenuicollis)
      through visual inspection, incision and palpation of organs and viscera. RESULTS:
      The prevalence of echinococcosis was 22.2% and 16.6%, in goats and sheep,
      respectively, while the overall infection rates for cysticercosis were 61.1% in
      goats and 42.2% in sheep. The result of this study revealed that goats and sheep
      in Malambo slaughter slab had significantly higher prevalence of T. hydatigena
      (C. tenuicollis) and hydatid cysts (p<0.05) compared to other slab points. T.
      hydatigena (C. tenuicollis) cysts were more frequently detected in the omentum
      than other visceral organs among the animals examined. CONCLUSION: In conclusion,
      the observed high prevalence of the two metacestodes larval stages leads to high
      condemnation rates of edible offals and raises significant public health
      concerns. This underscores for the need to undertake more extensive
      epidemiological investigations to better determine the causal factors, economic
      impact, and public health importance of the disease in this livestock-wildlife
      interface setting.

PMID- 28507414
TI  - A reducing trend of fasciolosis in slaughtered animals based on abattoir data in
      South of Iran.
AB  - AIM: Fascioliasis is a zoonosis infection caused by the liver trematodes
      (Fasciola spp.) which have been considered to be an important disease in
      livestock. After several large outbreaks, fascioliasis remains one of the serious
      health concerns of Iran. This study was conducted to evaluate the prevalence and
      possible trends of fascioliasis in slaughtered animals in South of Iran based on
      abattoir data during a period of 5 years. MATERIALS AND METHODS: The daily
      records for cattle, sheep, and goats slaughtered in the abattoir were extracted
      from the archived documents of the recent 5 years (2011-2015) and used as the
      source of data. The collected data were statistically analyzed for finding any
      probable correlation between the various factors associated with fasciolosis.
      RESULTS: Our results showed that 3.44% of all slaughtered animals during 2011
      2015 were infected with Fasciola spp. The mean prevalence of fasciolosis for
      cattle, sheep, and goat was 11.15%, 5.22%, and 2.15%, respectively. In addition,
      the highest infection rate was in winter (4.02%), and the lowest were entered in
      summer (2.86%). CONCLUSION: Our findings showed a reducing trend during the 5
      years. Improving the animal husbandry and increasing the awareness through
      fasciolosis may be a logical explanation for this trend. Since there have been
      suggested numerous factors associated with the epidemiology of fasciolosis,
      further studies seem essential for better clarifying the various aspects of
      fasciolosis in areas.

PMID- 28507415
TI  - Prospects of complete feed system in ruminant feeding: A review.
AB  - Effective utilization of available feed resources is the key for economical
      livestock rearing. Complete feed system is one of the latest developments to
      exploit the potential of animal feed resources in the best possible way. The
      complete feed is a quantitative mixture of all dietary ingredients, blended
      thoroughly to prevent separation and selection, fed as a sole source of nutrients
      except water and is formulated in a desired proportion to meet the specific
      nutrient requirements. The concentrate and roughage levels may vary according to
      the nutrient requirement of ruminants for different production purposes. The
      complete feed with the use of fibrous crop residue is a noble way to increase the
      voluntary feed intake and thus animal's production performance. In this system of
      feeding, the ruminant animals have continuous free choice availability of uniform
      feed mixture, resulting in more uniform load on the rumen and less fluctuation in
      release of ammonia which supports more efficient utilization of ruminal non
      protein nitrogen. Feeding complete diet stabilizes ruminal fermentation, thereby
      improves nutrient utilization. This feeding system allows expanded use of agro
      industrial by-products, crop residues and nonconventional feeds in ruminant
      ration for maximizing production and minimizing feeding cost, thus being
      increasingly appreciated. However, to extend the concept extensively to the field
      and make this technology successful and viable for farmers, more efforts are
      needed to be taken.

PMID- 28507416
TI  - Pathotypic characterization of Newcastle disease virus isolated from vaccinated
      chicken in West Java, Indonesia.
AB  - AIM: This research was conducted to differentiate and characterize eight
      Newcastle disease virus (NDV) isolates collected from vaccinated chicken at
      commercial flocks in West Java, Indonesia, in 2011, 2014 and 2015 by pathotype
      specific primers. MATERIALS AND METHODS: A total of eight NDV isolates collected
      from clinical outbreaks among commercial vaccinated flocks in West Java,
      Indonesia, in 2011, 2014, and 2015 were used in this study. Reverse transcription
      polymerase chain reaction was used to detect and differentiate virulence of NDV
      strains, using three sets of primers targeting their M and F gene. First primers
      were universal primers to detect NDV targeting matrix (M) gene. Other two sets of
      primers were specific for the fusion (F) gene cleavage site sequence of virulent
      and avirulent NDV strains. RESULTS: Our results showed that three isolates belong
      to NDV virulent strains, and other five isolates belong to NDV avirulent strains.
      The nucleotide sequence of the F protein cleavage site showed 112K/R-R-Q/R-K-R/G
      F117 on NDV virulent strains and 112G-K/R-Q-G-R-L117 on NDV avirulent strain.
      CONCLUSION: Result from the current study suggested that NDV virulent strain were
      circulating among vaccinated chickens in West Java, Indonesia; this might possess
      a risk of causing ND outbreaks and causing economic losses within the poultry
      industry.

PMID- 28507417
TI  - Molecular detection of Taenia spp. in dogs' feces in Zanjan Province, Northwest
      of Iran.
AB  - AIM: Echinococcus and Taenia spp. are important but neglected zoonotic helminths
      of dogs. Dogs as the most relevant definitive hosts harbor several species of
      Taenia and Echinococcus simultaneously in their gastrointestinal lumen which are
      morphologically indistinguishable. In this study, we used a multiplex polymerase
      chain reaction (PCR) method to identify Taeniid infections which seem to be
      highly distributed in the study region. MATERIALS AND METHODS: A total of 450 dog
      fecal samples were collected from eight different areas of Zanjan province,
      northwest of Iran, and examined using a flotation method followed by multiplex
      PCR for detection and identification of parasites' eggs. RESULTS:
      Gastrointestinal parasites were found in 86 out of 450 fecal samples (19.1%) by
      microscopic examination. Taeniid eggs were observed in 5.6% of samples,
      containing 0.45%, 3.8%, and 1.3% Echinococcus granulosus, Taenia spp., and mix
      infection of both E. granulosus and Taenia spp., respectively. Echinococcus
      multilocularis was absent in the samples. CONCLUSION: A relatively low rate of E.
      granulosus (1.8%) was observed in this study. However, risks of this parasite
      should not be overlooked, and control programs need to be extended for this
      species and other Taeniid spp. In particular, dogs are recommended to be dewormed
      more frequently.

PMID- 28507418
TI  - Spatial pattern of foot-and-mouth disease virus serotypes in North Central
      Nigeria.
AB  - AIM: This study aimed to determine the foot-and-mouth disease virus (FMDV)
      serotypes circulating, the prevalence of FMDV serotypes, and the spatial
      distribution of FMDV among sedentary and pastoral cattle herds in the North
      Central Nigeria. MATERIALS AND METHODS: A cross-sectional study was undertaken,
      during which a total of 155 sera that tested positive for foot-and-mouth disease
      (FMD) 3ABC non-structural protein antibodies were selected and screened for FMD
      structural protein serotypes, A, O, SAT 1, and SAT 2 using a solid-phase
      competitive enzyme-linked immunosorbent assay (ELISA). Epithelial tissue
      specimens were collected during outbreak investigations which were tested for FMD
      using an antigen capture ELISA for serotype A, O, SAT 1, and SAT 2. RESULTS: An
      overall serotype-specific prevalence of 79.35 (95% confidence interval [CI]: 72.4
      85.18) was recorded for serotype O, 65.2% (95% CI: 57.41-72.3) for serotype A,
      52.9% (95% CI: 45.03-60.67) for SAT 2, and 33.55% (95% CI: 26.45-41.26) for SAT
      1. Evidence of exposure to multiple FMDV serotypes showed that 12.26% of the sera
      samples had antibodies against four serotypes circulating, 30.97% had antibodies
      against three serotypes circulating, 22.58% had antibodies against two serotypes,
      and 17% showed exposure to only one serotype. Clinical specimens (epithelial
      tissue) collected during outbreak investigations showed that serotype O has the
      highest proportion of 50% with serotype A - 25%; SAT 2 - 20.8%; and SAT 1 - 4.1%.
      CONCLUSION: The study detected diffuse and co-circulation of serotypes A, O, SAT
      1, and SAT 2 within the study area, and hence the need for the appropriately
      matched multivalent vaccine is strongly advocated for FMD control in Nigeria.

PMID- 28507420
TI  - Some hematological and biochemical parameters of different goat breeds in
      Sultanate of Oman "A preliminary study".
AB  - AIM: In Sultanate of Oman, goats are considered as one of the most important
      livestock in which there are many breeds of goat such as Batinah, Jabali,
      Dhofari, Jabal Al-Akhdar, Sahrawi, and Sahrawi Musandam. Little hematological and
      biochemical information is known on Omani goat breeds; therefore, the main
      purpose of this study was to determine reference baseline data regarding
      hematological and biochemical values of different Omani goat breeds. MATERIALS
      AND METHODS: A total of 30 healthy animals of different Omani goat breeds
      (Jabali, Jabal Al-Akhdar, Sahrawi, and Sahrawi Musandam) were selected randomly
      from different areas in Sultanate of Oman. The blood samples were collected from
      the jugular vein into two tubes for blood hematology and biochemical analysis.
      Statistical analysis was applied by using GraphPad Prism 7 software to calculate
      the minimum and maximum values to determine the range, mean, standard deviation
      of the mean and the p value. RESULTS: No statistically significant variation in
      most hematological and biochemical parameters was found among the Omani goat
      breeds. The results of blood hematology revealed that the mean white blood cells
      (14.6+/-3.32 *103/uL), and the percentage of neutrophils in Omani goats (60.87+/
      8.46%) were higher than that in most goat breeds. Higher values of red blood
      cells (12.8+/-1.28 *106/uL), hemoglobin (10.4+/-1.92 g/dl), hematocrit (38.29+/
      4.06%), and lower values of mean corpuscular HGB concentration (27.05+/-3.5 g/dl)
      were observed in Omani goat breeds comparing to that in the other goat breeds.
      Lower values of total bilirubin (0.22+/-0.03 mg/dl), blood urea nitrogen (14.62+/
      2.66 mg/dl), and cholesterol (48.58+/-19.05 mg/dl) were found in Omani goat
      breeds when compared to that of the other goat breeds. CONCLUSION: The obtained
      results are considered as the first values to be published for the different
      Omani goat breeds. This study is considered as preliminary study which can be
      used as a reference for further studies to determine reference values for the
      studied breeds to aid the veterinarians in the interpretation of the laboratory
      data and for the selection of the appropriate treatment.

PMID- 28507419
TI  - Exploring the potential hazard of Mycobacterium avium subspecies paratuberculosis
      as a cause for Crohn's disease.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is the
      causative agent of Johne's disease (JD), or paratuberculosis in ruminants has
      been suspected to be implicated in the pathogenesis of Crohn's disease (CD) in
      humans with chronic inflammatory intestinal changes. As the hypothesis is now
      fast being recognized that MAP could possibly be the etiological agent of CD
      which is found to be excreted in milk of dairy animals subclinically or
      terminally ill with JD. AIM: The present study was aimed to detect MAP in milk by
      polymerase chain reaction (PCR) targeting IS900 and to describe the excretion
      pattern of MAP in milk from asymptomatic lactating cows and does with relevance
      to the public health significance. MATERIALS AND METHODS: A total of 77 milk
      samples were collected randomly from lactating animals which include cows (45)
      and does (32). All the 77 milk samples were processed to identify the presence of
      MAP by employing the direct IS900 PCR as per the standard protocol. RESULTS: Out
      of 77 milk samples from asymptomatic lactating animals, 12 (15.58%) were showed
      positivity for IS900 PCR in which 5 (11.11%) were from lactating cows and 7
      (21.87%) were from lactating does. CONCLUSION: In our study, 15.58% of milk
      samples showed IS900 positivity which indicates the presence of subclinical MAP
      infection in lactating animals. Hence, there is a possibility for excretion of
      MAP through milk which can be a potential threat for CD in humans by raw milk
      consumption. Therefore, the prevention of MAP in the food chain need to be
      assured by sourcing raw products from animal herds free of MAP infection.

PMID- 28507421
TI  - Orthopaedic tumors: What problems are we solving, and are universities and major
      medical centers doing enough?
AB  - Little has been published about the complexity of orthopaedic tumors compared to
      others tumors. The current study in the literature treated this problem in terms
      of classification, surgical intervention and impact on the patient. In this
      article, factors risks of tumors will be we identified. A strategy based on three
      dimensional simulations will be explained in order to improve the clinical
      trials.

PMID- 28507422
TI  - Understanding the Spectrum of SLC2A1-Associated Disorders.
AB  - Investigators from the Danish Epilepsy Center the frequency of SLC2A1 mutations
      in a cohort of patients with different types of epilepsies.

PMID- 28507423
TI  - Lacosamide in Pediatric Status Epilepticus.
AB  - Investigators from Baylor College of Medicine studied the efficacy of lacosamide
      in pediatric status epilepticus (SE).

PMID- 28507424
TI  - Migraine, Celiac Disease and Intestinal Microbiota.
AB  - Investigators from four European tertiary care hospitals (in Paris, France;
      Milan, Udine and Perugia, Italy) performed a case-control study of children and
      adolescents aged 6 to 17 years diagnosed with primary headaches in the emergency
      department by a pediatric neurologist using the validated ICHD-3 criteria.

PMID- 28507425
TI  - A Multigroup, Longitudinal Study of Truant Youths, Marijuana Use, Depression, and
      STD-Associated Sexual Risk Behavior.
AB  - Truant youth are likely to engage in a number of problem behaviors, including
      sexual risky behaviors. Previous research involving non-truant youth has found
      sexual risk behaviors to be related to marijuana use and depression, with
      differential effects for male and female youth. Using data collected in a NIDA
      funded, prospective intervention project, results are reported of a male-female,
      multi-group, longitudinal analysis of the relationships among truant youth
      baseline sexual risk behavior, marijuana use, and depression, and their sexual
      risk behavior over four follow-up time points. Results indicated support for the
      longitudinal model, with female truants having higher depression scores, and
      showing stronger relationships between baseline depression and future engagement
      in sexual risk behavior, than male truants. Findings suggest that incorporating
      strategies to reduce depression and marijuana use may decrease youth sexual risk
      behavior.

PMID- 28507427
TI  - The Sensimed Triggerfish contact lens sensor: efficacy, safety, and patient
      perspectives.
AB  - Intraocular pressure, a major modifiable risk factor for glaucoma, has been shown
      to fluctuate throughout the day in patients with glaucoma. The detection and
      measurement of this fluctuation may help guide the clinical management of
      glaucomatous individuals. The Sensimed Triggerfish contact lens sensor (CLS),
      which has recently gained approval for marketing in the USA, is designed to
      detect intraocular pressure-related changes in an eye over a 24-hour period. This
      review will provide an overview of the Triggerfish CLS, as well as summarize
      current clinical data pertaining to the device. Overall, the current evidence
      suggests that the Triggerfish CLS is safe and well tolerated, and provides
      reproducible results. One challenge of using the Triggerfish CLS is that it may
      only provide data on relative changes in intraocular pressure rather than
      absolute intraocular pressure. In addition, its validity at estimating
      intraocular pressure compared to other methods is still controversial. Despite
      these limitations, recent studies suggest a myriad of potential indications for
      the Triggerfish CLS, including predicting glaucomatous progression and predicting
      efficacy of glaucoma treatment. With further research, the Triggerfish CLS may
      become a useful tool for eye care practitioners.

PMID- 28507426
TI  - Performance of High School Students in a Laparoscopic Training Program.
AB  - BACKGROUND AND OBJECTIVES: We hypothesized that high school students can be
      subjected to the same laparoscopic surgical training curriculum used by surgeons
      and successfully complete it. The goal of this study was to evaluate the
      appropriateness of early training in minimally invasive surgical techniques.
      METHODS: Thirteen high school students, ages 15-18, participated in the validated
      Top Gun Surgeon Laparoscopic Skills and Suturing program. The students performed
      3 preparatory drills 10 times each. The students' scores were then compared to a
      database of 393 surgeons. Performance graphs were prepared to allow comparison of
      skills acquisition between the 2 training groups. RESULTS: All 13 students
      successfully completed the tasks. The Students' performance (expressed as
      time/percentile range/average percentile) for each task were as follows: rope
      pass 101.8 seconds/3.8-47.1/11.8; bean drop 149.5 seconds/18.7-96.0/59.4;
      triangle transfer 303.2 seconds/1.3-16.0/5.8. The students started each drill
      with slower times, but their average improvement (decreased time to complete
      tasks) was more rapid than that of the surgeons between the first and second
      trials for each drill (-83 seconds vs -25 seconds, -120 seconds vs -53 seconds, 
      100 seconds vs -60 seconds). Average student times compared to average surgeon
      times during the last trials measured were not significantly different in the
      triangle transfer and rope pass drills (P = .40 and .18, respectively). Students'
      times were significantly faster than surgeons' in the last measured trial of the
      bean drop (P = .039). CONCLUSIONS: Despite the small sample size, this
      investigation suggests that high school students can successfully complete skill
      building programs in minimally invasive surgery. Further study is needed to
      evaluate the appropriateness of starting surgical training of future residents at
      an earlier stage of their careers.

PMID- 28507429
TI  - Factors associated with the attitudes of oncology nurses toward hospice care in
      China.
AB  - OBJECTIVE: To examine factors that are associated with the apprehension levels of
      oncology nurses toward hospice care. Factors examined in this study included
      demographics, nursing experience, education levels, title and post, personal
      experiences, and attitudes toward end-of-life care. METHODS: Questionnaires were
      provided to nurses (n=201) from three first-tier hospitals in China. A
      quantitative scale, Professional End-of-life Care Attitude Scale (PEAS), was used
      to assess personal and professional apprehension levels toward hospice care. The
      PEAS was translated to Chinese with terms adapted to the cultural environment in
      China. Statistical analyses were performed to examine the relationships between
      the apprehension levels and various factors. RESULTS: The total PEAS scores
      exhibited internal consistency and reliability, with a Cronbach alpha=0.897 and
      Pearson's r=0.9030. Of the 201 nurses, 184 provided a valid response (91.5%).
      Education level was significantly correlated with personal (P<0.01) and
      professional apprehension levels (P<0.05). Higher apprehension level was found in
      nurses with less education. CONCLUSION: The PEAS quantitative survey is useful
      for evaluating apprehension levels of nurses toward hospice care. Nurses with
      more education experienced less anxiety when providing care for terminally ill
      patients. The findings suggested that education programs on hospice care could be
      strengthened to help nurses cope with negative attitudes toward end-of-life care.

PMID- 28507430
TI  - Investigating the feasibility of text message reminders to improve adherence to
      nebulized medication in children and adolescents with cystic fibrosis.
AB  - BACKGROUND: Children with cystic fibrosis (CF) often have suboptimal adherence
      rates to nebulized medication. Adherence barriers cited include forgetting to
      take the nebulizers, due to busy home and social lives. Text message reminders
      have been shown to be effective at improving adherence rates in other chronic
      diseases such as asthma and diabetes. OBJECTIVE: The objective of this study was
      to assess the feasibility and efficacy of sending text reminders for a prolonged
      period of time to children with CF. MATERIALS AND METHODS: Children with CF aged
      5-16 years taking at least one medication via a nebulizer with an electronic
      adherence monitor were consented for the study. Text message reminders were sent
      to participants and/or parents via the hospital's automated text service, up to
      twice a day, for 6 months. The adherence rates for the 6-month text period were
      compared to the previous 6 months before the study. Rates were calculated for
      weekdays, weekends, and school holidays. RESULTS: Seventeen participants were
      recruited to the study, with a mean age of 12 years and a mean forced expiratory
      volume in 1 second (FEV1) of 81% predicted. Fifteen children completed the 6
      month text period, and I-neb data were accurately analyzed for 13 participants.
      The mean adherence rate in the 6 months receiving texts was 80%, compared to 81%
      in the prior 6 months. Overall adherence rates on weekdays, weekends, and school
      holidays were equivalent during the 2 time periods. A subgroup of patients with
      moderate baseline adherence showed increased adherence during the text period,
      particularly at weekends. CONCLUSION: It is feasible to send text message
      reminders to children with CF, and they are amenable to this approach. Although
      text reminders do not increase rates in patients with existing optimal adherence,
      they may be of value in patients with more moderate baseline rates.

PMID- 28507428
TI  - Propranolol therapy for infantile hemangioma: our experience.
AB  - OBJECTIVE: Hemangiomas are the most common benign vascular tumors of infancy.
      Although most infantile hemangiomas (IHs) have the ability to involute
      spontaneously after initial proliferation and resolve without consequence,
      intervention is required in a subset of IHs, which develop complications
      resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment
      for this subset of IHs is pharmacological intervention, and propranolol has
      become the new first-line treatment for complicated hemangiomas. Here, we
      evaluated the efficacy of propranolol on proliferation IH in a clinical cohort
      including 578 patients. METHODS: We retrospectively reviewed a total of 578 IH
      patients who were treated with oral propranolol from January 2010 to December
      2012. Responses to the propranolol treatment were graded as: excellent, good,
      poor, or no response. Based on the response to propranolol treatment (once daily
      at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily
      total dose of 2 mg/kg for patients older than 2 months), additional
      pharmacotherapies or surgery were used for IH patients for satisfactory clinical
      outcome. RESULTS: Five hundred and sixty (96.9%) of 578 IH patients in our study
      responded to oral propranolol treatment, and the response rate was significantly
      different for different ages of patients (P<0.05), with the youngest patients
      having the highest response rate. The mean time of treatment was 6 months (range,
      3-12 months). For example, response rate to propranolol was 98.1% in patients
      younger than 2 months, compared with 93.3% in patients older than 2 months and
      younger than 8 months, and 73.7% in patients older than 8 months. One hundred and
      thirty one patients who exhibited incompletely involuted hemangiomas were further
      treated with timolol maleate (n=89) or pulsed dye laser (n=42). One hundred and
      seventeen (89.3%) of 131 patients showed a positive response. There were no
      instances of life-threatening complications after propranolol. However, minor
      side effects were observed including 10 (1.73%) cases of sleep disturbance, 7
      (1.21%) cases of diarrhea, and 5 (0.86%) cases of bronchospasm. CONCLUSION: IH
      requires early intervention. During the involution phase, tapering propranolol
      dosage can be done to minimize side effects before discontinuing treatment. For
      patients exhibiting telangiectasia and chromatosis after propranolol treatment,
      administration of a 0.5% solution of timolol maleate or pulse dye laser is an
      effective therapeutic approach for complete involution.

PMID- 28507431
TI  - Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32
      randomized clinical trials.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease and
      ultimately leads to right heart failure and premature death. A total of four
      classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs),
      phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase
      stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics
      compared to placebo; however, direct head-to-head comparisons of these drugs are
      lacking. This network meta-analysis was conducted to comprehensively compare the
      efficacy of these targeted drugs for PAH. METHODS: Medline, the Cochrane Library,
      and other Internet sources were searched for randomized clinical trials exploring
      the efficacy of targeted drugs for patients with PAH. The primary effective end
      point of this network meta-analysis was a 6-minute walk distance (6MWD). RESULTS:
      Thirty-two eligible trials including 6,758 patients were identified. There was a
      statistically significant improvement in 6MWD, mean pulmonary arterial pressure,
      pulmonary vascular resistance, and clinical worsening events associated with each
      of the four targeted drugs compared with placebo. Combination therapy improved
      6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003) vs
      prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008) vs ERAs. PDE-5Is improved
      6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028) vs prostanoids, with a similar
      result with combination therapy. In addition, combination therapy reduced mean
      pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001) vs
      prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001) vs ERAs, 3.38 mmHg (95%
      CI: -6.30, -0.47; P=0.023) vs PDE-5Is, and 3.94 mmHg (95% CI: -6.99, -0.88;
      P=0.012) vs sGCS. There were no significant differences in all-cause mortality
      and severe adverse events between prostanoids, ERAs, PDE-5Is, sGCS, combination
      therapy, and placebo. CONCLUSION: All targeted drugs for PAH are associated with
      improved clinical outcomes, especially combination therapy. However, all these
      drugs seem to show less favorable effects on survival in the short-term follow
      up, suggesting further clinical trials are required.

PMID- 28507432
TI  - The effects of patient and physician characteristics on early outpatient
      satisfaction with substance dependence care: results of the SUBUSQOL study.
AB  - BACKGROUND: Although patient perceptions of health care have increasingly been
      explored in the literature, little is known about care satisfaction among
      individuals with substance dependence. This exploratory study assessed the
      relationships between patient and physician characteristics and early outpatient
      satisfaction with care for alcohol and opioid dependence. METHODS: Satisfaction
      was assessed using a multidimensional, self-administered and validated
      questionnaire during the early care process among a prospective outpatient
      cohort. In addition to measuring satisfaction and obtaining sociodemographic and
      clinical data, this study collected data on the self-reported health status and
      physician characteristics at inclusion. Cross-sectional analysis with multiple
      linear regression was performed to identify the variables associated with
      satisfaction level. RESULTS: A total of 249 outpatients were included, and 63.8%
      completed the satisfaction questionnaire. Patients without a history of previous
      care for substance dependence were more satisfied with the appointment-making
      process (beta=7.2; P=0.029) and with the doctor consultation (beta=10.3; P=0.003)
      than those who had received care previously. Neither sociodemographic
      characteristics nor self-reported health status was associated with outpatient
      satisfaction. CONCLUSION: The factors that affect patients' ratings of early
      satisfaction with the care that they receive should be studied further because
      increased understanding of the factors that negatively affect these ratings might
      enable caregivers and outpatient management facilities to improve the patient
      experience during the early stages of care, which might in turn improve treatment
      adherence, continuity of care, and other health-related outcomes.

PMID- 28507433
TI  - Effect of pharmaceutical care on clinical outcomes of outpatients with type 2
      diabetes mellitus.
AB  - BACKGROUND: In the People's Republic of China, outpatients have limited time with
      their physicians. Thus, compared to inpatients, outpatients have lower medication
      adherence and are less knowledgeable about their disease. OBJECTIVE: The
      objective of this study was to evaluate the effect of pharmaceutical care on
      clinical outcomes of outpatients with type 2 diabetes mellitus (T2DM). PATIENTS
      AND METHODS: A randomized, controlled, prospective clinical trial was conducted
      recruiting a total of 240 T2DM outpatients from Zhongda Hospital, Southeast
      University. The control group (CG) received only common care from medical staff,
      whereas the inter vention group (IG) received extra pharmaceutical care from
      clinical pharmacists. Biochemical data such as blood pressure (BP), fasting blood
      glucose (FBG), glycosylated hemoglobin A1 (HbA1c), and blood lipid were collected
      before and after 6-month intervention. The primary end points in this study were
      FBG and HbA1c. RESULTS: After the intervention, most of the baseline clinical
      outcomes of the patients in IG significantly improved, while only body mass
      index, diastolic BP, low-density lipoprotein cholesterol, and total cholesterol
      (TC) improved significantly in patients in the CG. Compared to CG, in IG, there
      were significant improvements in FBG, HbA1c, TC, the target attainment rates of
      HbA1c, and BP. CONCLUSION: Pharmaceutical care provided by clinical pharmacists
      could improve the control of diabetes of outpatients, and clinical pharmacists
      could play an important role in diabetes management.

PMID- 28507434
TI  - Enhanced oral bioavailability of valsartan using a polymer-based supersaturable
      self-microemulsifying drug delivery system.
AB  - A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was
      successfully formulated to enhance the dissolution and oral absorption of
      valsartan (VST), a poorly water-soluble drug, while reducing the total quantity
      for administration. Poloxamer 407 is a selectable, supersaturating agent for VST
      containing SMEDDS composed of 10% Capmul(r) MCM, 45% Tween(r) 20, and 45%
      Transcutol(r) P. The amounts of SMEDDS and Poloxamer 407 were chosen as
      formulation variables for a 3-level factorial design. Further optimization was
      established by weighting different levels of importance on response variables for
      dissolution and total quantity, resulting in an optimal S-SMEDDS in large
      quantity (S-SMEDDS_LQ; 352 mg in total) and S-SMEDDS in reduced quantity (S
      SMEDDS_RQ; 144.6 mg in total). Good agreement was observed between predicted and
      experimental values for response variables. Consequently, compared with VST
      powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed
      excellent in vitro dissolution and in vivo oral bioavailability in rats. The
      magnitude of dissolution and absorption-enhancing capacities using quantity-based
      comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or
      suspension. Thus, we concluded that, in terms of developing an effective SMEDDS
      preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate.

PMID- 28507437
TI  - Changing health care culture: a prerequisite to improving patient safety.

PMID- 28507436
TI  - Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (epsilon
      caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer
      metastasized to bone.
AB  - Treatment of cancer metastasized to bone is still a challenge due to
      hydrophobicity, instability, and lack of target specificity of anticancer drugs.
      Poly (ethylene glycol)-poly (epsilon-caprolactone) polymer (PEG-PCL) is an
      effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks
      bone specificity. Polyaspartic acid with eight peptide sequences, that is,
      (Asp)8, has a strong affinity to bone surface. The aim of this study was to
      synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic
      drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance,
      Fourier transform infrared spectroscopy, and transmission electron microscopy
      data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized
      successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte
      aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded
      (Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did
      not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at
      the concentration of 10-800 MUg/mL. (Asp)8-PEG-PCL nanoparticles bound with
      hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL
      nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG
      PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties.
      Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading
      capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded
      (Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for
      >8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong
      antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion,
      (Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent
      carrier, and an efficient releaser of hydrophobic anticancer drug and were bone
      specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong
      antitumorigenic ability in vitro. Therefore, (Asp)8-PEG-PCL nanoparticles could
      be a potent carrier of hydrophobic anticancer drugs to treat the cancer
      metastasized to bone.

PMID- 28507435
TI  - Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and
      perturb neuronal network activity in a size- and time-dependent manner.
AB  - PURPOSE: Mesoporous silica nanoparticles (MSNPs) are excellent candidates for
      biomedical applications and drug delivery to different human body areas, the
      brain included. Although toxicity at cellular level has been investigated, we are
      still far from using MSNPs in the clinic, because the mechanisms involved in the
      cellular responses activated by MSNPs have not yet been elucidated. MATERIALS AND
      METHODS: This study used an in vitro multiparametric approach to clarify
      relationships among size, dose, and time of exposure of MSNPs (0.05-1 mg/mL dose
      range), and cellular responses by analyzing the morphology, viability, and
      functionality of human vascular endothelial cells and neurons. RESULTS: The
      results showed that 24 hours of exposure of endothelial cells to 250 nm MSNPs
      exerted higher toxicity in terms of mitochondrial activity and membrane integrity
      than 30 nm MSN at the same dose. This was due to induced cell autophagy (in
      particular mitophagy), probably consequent to MSNP cellular uptake (>20%).
      Interestingly, after 24 hours of treatment with 30 nm MSNPs, very low MSNP uptake
      (<1%) and an increase in nitric oxide production (30%, P<0.01) were measured.
      This suggests that MSNPs were able to affect endothelial functionality from
      outside the cells. These differences could be attributed to the different protein
      corona composition of the MSNPs used, as suggested by sodium dodecyl sulfate
      polyacrylamide-gel electrophoresis analysis of the plasma proteins covering the
      MSNP surface. Moreover, doses of MSNPs up to 0.25 mg/mL perturbed network
      activity by increasing excitability, as detected by multielectrode-array
      technology, without affecting neuronal cell viability. CONCLUSION: These results
      suggest that MSNPs may be low-risk if prepared with a diameter <30 nm and if they
      reach human tissues at doses <0.25 mg/mL. These important advances could help the
      rational design of NPs intended for biomedical uses, demonstrating that careful
      toxicity evaluation is necessary before using MSNPs in patients.

PMID- 28507438
TI  - Pulmonary hypertension in Nigerian adults with sickle cell anemia.
AB  - BACKGROUND: Sickle cell anemia (SCA) is the commonest hemoglobinopathy and is
      associated with high morbidity and mortality. Pulmonary hypertension (PH) is
      reported to play a significant role in this regard. There is very limited
      literature on PH in SCA in Nigeria. OBJECTIVES: The objectives of this study were
      to determine the prevalence of Doppler-derived PH in SCA, assess its influence on
      exercise capacity, and determine the correlates and predictors of measures of
      estimated pulmonary pressure. METHODS: A total of 92 SCA subjects had
      echocardiography and 6-minute self-paced walking exercise. PH was diagnosed by
      Doppler echocardiography on finding a tricuspid regurgitant velocity (TRV) of
      >=2.5 m/s. The pulmonary flow profile was also assessed to estimate mean
      pulmonary arterial pressure (MPAP). RESULTS: Doppler-derived PH was detected in
      23.9% of adults with SCA. The 6-minute walking distance (6MWD) was significantly
      lower in SCA adults with PH than in those without PH (380.33 +/- 63.17 m vs
      474.28 +/- 76.74 m; p = 0.014). TRV and estimated MPAP had a significant inverse
      correlation with the 6MWD (r = -0.442; p < 0.001 and r = -0.571; p < 0.001,
      respectively). CONCLUSION: PH as derived by Doppler is common in Nigerian adults
      with SCA and has a significantly negative influence on exercise capacity.
      Screening for PH should be encouraged to optimize management and thus improve
      their quality of life and life expectancy.

PMID- 28507440
TI  - Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and
      treatment.
AB  - Basal cell carcinoma (BCC) is a common malignant tumor throughout the world. One
      of the known risk factors of BCC is intense exposure to ultraviolet radiation.
      More than 50% of BCCs of the eyelid initially occur on the lower lid. The gold
      standard of diagnosis of BCC is histopathology. Treatment options for BCC consist
      of surgery, vismodegib, radiotherapy and imiquimod. Surgical excision using Mohs
      micrographic surgery or wide surgical excision with frozen section margin control
      is the first consideration for treatment of periocular BCC. Eyelid reconstruction
      should be carefully considered as both function and esthetic outcome in patients
      are important after clear excision of tumors. Exenteration is considered in the
      case of extensive orbital invasion or high-risk aggressive tumors in order to
      reduce the rate of recurrence.

PMID- 28507441
TI  - Clinicopathological significance of p14ARF expression in lung cancer: a meta
      analysis.
AB  - BACKGROUND: p14ARF, a tumor suppressor protein, encoded by the p16 tumor
      suppressor gene, has been reported to be associated with the clinicopathological
      features of lung cancer. However, the evaluated outcomes were inconsistent and
      remained inconclusive. In this study, we conducted a meta-analysis to clarify the
      significance of p14ARF expression in lung cancer pathogenesis. MATERIALS AND
      METHODS: Electronic databases, PubMed, Web of Knowledge, Embase, and CNKI, were
      retrieved to collect relevant articles with inclusion and exclusion criteria.
      Using Stata 12.0 software, 95% confidence intervals (CIs) and odds ratios (ORs)
      were calculated. RESULTS: A total of 15 eligible case-control studies that
      evaluated the relationship between p14ARF expression and lung cancer were
      included in the meta-analysis. The results demonstrated that there were
      significant associations between p14ARF expression and the risk of non-small-cell
      lung cancer (NSCLC), lung adenocarcinoma, and lung squamous carcinoma (for NSCLC,
      OR =11.02, 95% CI =5.30-22.92; for lung adenocarcinoma, OR =7.28, 95% CI =3.92
      13.50; and for lung squamous carcinoma, OR =14.40, 95% CI =2.83-73.24). In the
      stratified analysis based on race, significant associations between p14ARF
      expression and lung cancer risk were found in Chinese population and Caucasians
      (for Chinese population, OR = 7.02, 95% CI =4.48-11.00 and for Caucasians, OR
      =4.19, 95% CI =1.42-12.38). Furthermore, the expression of p14ARF was
      significantly associated with the TNM-stage of lung cancer in Chinese population
      (OR =2.07, 95% CI =1.38-3.10). CONCLUSION: p14ARF expression was significantly
      associated with the risk of lung cancer. In addition, the data of the meta
      analysis showed that there was a significant correlation between p14ARF
      expression and the TNM-stage of lung cancer in Chinese population.

PMID- 28507439
TI  - Infrainguinal open reconstruction: a review of surgical considerations and
      expected outcomes.
AB  - Infrainguinal arterial occlusive disease can lead to potentially disabling and
      limb-threatening conditions. Revascularization may be indicated for claudication,
      rest pain, or tissue loss. Although endovascular interventions are becoming more
      prevalent, open surgeries such as endarterectomy and bypass are still needed and
      performed regularly. Open reconstruction has been associated with postoperative
      morbidity, both at the local and at the systemic levels. Local complications
      include surgical site infections (SSIs 0-5.3%), graft failure (12-60%), and
      amputation (5.7-27%), and more systemic issues include cardiac (2.6-18.4%),
      respiratory (2.5%), renal (4%), neurovascular (1.5%), and thromboembolic (0.2-1%)
      complications. While such outcomes present an additional challenge to the
      postoperative management of surgical patients, it may be possible to minimize
      their occurrence through careful risk stratification and preoperative assessment.
      Therefore, individualized selection of candidates for open repair requires
      weighing the need for intervention against the likelihood of adverse outcomes
      based on preoperative risk factors. This review provides an overview of open
      reconstruction, focusing on identifying the clinical indications for surgery and
      perioperative morbidity and mortality.

PMID- 28507443
TI  - Erratum: Retinoic acid and arsenic trioxide in the treatment of acute
      promyelocytic leukemia: current perspectives [Corrigendum].
AB  - [This corrects the article on p. 1585 in vol. 10, PMID: 28352191.].

PMID- 28507442
TI  - Aberrant promoter methylation profiles and association with survival in patients
      with hepatocellular carcinoma.
AB  - The aim of this study was to investigate the prognostic and diagnostic value of
      genes with promoter methylation in hepatocellular carcinoma (HCC) patients. On
      the basis of The Cancer Genome Atlas data, we identified genes with
      differentially methylated promoters in HCC tissues and adjacent non-tumor
      tissues, using the linear models for microarray data approach. Cox proportional
      hazard regression analysis was applied to access the prognostic value of
      identified differentially methylated genes. The diagnostic value of the genes was
      evaluated through receiver operating characteristic. Pathway analyses were
      performed to illustrate biological functions of the identified genes. Compared to
      adjacent tissues, 77 genes with hypermethylated promoters and 2,412 genes with
      hypomethylated promoters were identified in HCC. The promoter hypomethylations of
      RNA5SP38, IL21, SDC4P, and MIR4439 were found to be associated with HCC patient
      survival (P=0.035, 0.040, 0.004, and 0.024, respectively). Hypomethylated SDC4P
      was associated with a better prognosis (hazard ratio, 0.482; 95% confidence
      interval [CI], -0.147-1.110; P=0.007). The combination of the promoter
      hypomethylations with RNA5SP38, IL21, and SDC4P showed an area under receiver
      operating characteristic curves of 0.975 (95% CI, 0.962-0.989; P=4.811E-25).
      Several pathways, including olfactory transduction, cytokine-cytokine receptor
      interaction, natural killer cell-mediated cytotoxicity, as well as inflammation
      mediated by chemokine and cytokine signaling pathway, were annotated with the
      hypomethylated promoter genes. SDC4P promoter hypomethylation may be a potential
      prognosis biomarker. A panel of promoter methylations in RNA5SP38, IL21, and
      SDC4P was proven a novel approach to diagnosis HCC. The pathway analysis defined
      the extensive functional role of DNA hypomethylation in cancer.

PMID- 28507444
TI  - Antibodies against glutamic acid decarboxylase and indices of insulin resistance
      and insulin secretion in nondiabetic adults: a cross-sectional study.
AB  - BACKGROUND: Autoimmunity against insulin-producing beta cells from pancreatic
      islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes
      in adults. Some reports have also related beta-cell autoimmunity to insulin
      resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity
      against components of beta cells is present and relates to IR and insulin
      secretion in nondiabetic adults is uncertain. AIM: To explore the association
      between antibodies against glutamic acid decarboxylase (GADA), a major antigen
      from beta cells, and indices of whole-body IR and beta-cell capacity/insulin
      secretion in adults who do not have diabetes. METHODS: We studied 81 adults of
      both sexes aged 30-70, without known diabetes or any autoimmune disease.
      Participants underwent an oral glucose tolerance test (OGTT) with determination
      of plasma glucose and insulin at 0, 30, 60, 90, and 120 minutes. From these
      results we calculated indices of insulin resistance (homeostasis model assessment
      of insulin resistance [HOMA-IR] and incremental area under the insulin curve
      [iAUCins]) and insulin secretion (corrected insulin response at 30 minutes and
      HOMA beta-cell%). GADAs were measured in fasting plasma using immunoenzymatic
      methods. RESULTS: We found an overall prevalence of GADA positivity of 21.3%,
      without differences by sex and no correlation with age. GADA titers did not
      change monotonically across quartiles of any of the IR or insulin secretion
      indices studies. GADA did not correlate linearly with fasting IR expressed as
      HOMA-IR (Spearman's r=-0.18, p=0.10) or postabsorptive IR expressed as iAUCins
      (r=-0.15, p=0.18), but did show a trend toward a negative correlation with
      insulin secretory capacity expressed by the HOMA-beta cell% index (r=-0.20,
      p=0.07). Hemoglobin A1c, body mass index, and waist circumference were not
      associated with GADA titers. CONCLUSION: GADA positivity is frequent and likely
      related to impaired beta-cell function among adults without known diabetes.

PMID- 28507446
TI  - Methotrexate: an effective monotherapy for refractory generalized morphea.
AB  - INTRODUCTION: Morphea is an inflammatory skin disorder characterized by excessive
      collagen deposition. Although treatment algorithms for morphea subtypes have been
      suggested, no consistent recommendations are available. This study attempts to
      evaluate the clinical efficacy of methotrexate (MTX) as monotherapy in refractory
      generalized morphea. METHODS: It is a retrospective study, including 20 patients
      who had already been treated with various topical and systemic therapies with
      minimal clinical improvement. Patients received orally MTX at a of dosage 15 mg
      once weekly. Duration of the use, dosage of MTX, and adverse events were
      recorded. Clinical assessment of skin lesions was performed and documented.
      RESULTS: The mean disease duration was 27 months before the initiation of MTX
      treatment. After 12 months of therapy, very good response was achieved in 6
      patients (30%), good response in 10 patients (50%), and fair response in 2
      patients (10%), while 2 patients (10%) had failed treatment. Patients were
      followed up for a mean time interval of 21 months. No serious adverse event was
      recorded. CONCLUSION: MTX has been already proved to be an effective and well
      tolerated treatment in pediatric patients with morphea. The majority of the group
      of adult patients showed very good and good improvement when treated with MTX.
      Although this is an uncontrolled study, MTX monotherapy was considered a safe and
      effective treatment for the management of this specific clinical subset of
      morphea in adults.

PMID- 28507445
TI  - Evaluation of fatigue and its correlation with quality of life index, anxiety
      symptoms, depression and activity of disease in patients with psoriatic
      arthritis.
AB  - BACKGROUND: Psoriatic arthritis is associated with psychosocial morbidity and
      decrease in quality of life. Psychiatric comorbidity also plays an important role
      in the impairment of quality of life and onset of fatigue. OBJECTIVES: This study
      aimed to assess the prevalence of fatigue in psoriatic arthritis patients and to
      correlate it to quality of life indexes, functional capacity, anxiety, depression
      and disease activity. PATIENTS AND METHODS: This cross-sectional study was
      performed on outpatients with psoriatic arthritis. Functional Assessment of
      Chronic Illness Therapy - Fatigue (FACIT-F; version 4) was used to measure
      fatigue; 36-Item Short Form Health Survey (SF-36) and Psoriasis Disability Index
      (PDI) to measure quality of life; Health Assessment Questionnaire (HAQ) to assess
      functional capacity; Hospital Anxiety and Depression (HAD) scale to measure
      anxiety and depression symptoms; Psoriasis Area and Severity Index (PASI), Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease
      Activity Index (CDAI) to evaluate clinical activity. RESULTS: In all, 101
      patients with mean age of 50.77 years were included. The mean PDI score was 8.01;
      PASI score, 9.88; BASDAI score, 3.59; HAQ score, 0.85; HAD - Anxiety (HAD A)
      score, 7.39; HAD Depression (HAD D) score, 5.93; FACIT-Fatigue Scale (FACIT-FS)
      score, 38.3 and CDAI score, 2.65. FACIT-FS was statistically associated with PASI
      (rs -0.345, p<0.001), PDI (rs -0.299, p<0.002), HAQ (rs -0.460, p<0.001), HAD A
      (rs -0.306, p=0.002) and HAD D (rs -0.339, p<0.001). The correlations with CDAI
      and BASDAI were not confirmed. There was statistically significant correlation
      with all of the domains of SF-36 and FACIT-F (version 4). CONCLUSION: Prevalence
      of fatigue was moderate to intense in <25% of patients with psoriatic arthritis.
      Fatigue seems to be more related to the emotional and social aspects of the
      disease than to joint inflammatory aspects, confirming that the disease's
      visibility is the most disturbing aspect for the patient and that "skin pain" is
      more intense than the joint pain.

PMID- 28507447
TI  - Managing refractory cryoglobulinemic vasculitis: challenges and solutions.
AB  - Cryoglobulinemia is thought to be a rare condition. It may be an isolated
      disorder or secondary to a particular disease. According to immunoglobulin
      composition, cryoglobulinemia is classified into three types. In mixed
      cryoglobulinemia (types II and III), vascular deposition of cryoglobulin
      containing immune complexes and complement may induce a clinical syndrome,
      characterized by systemic vasculitis and inflammation - cryoglobulinemic
      vasculitis (CryoVas). Most common clinical manifestations in CryoVas are skin
      lesions (orthostatic purpura and ulcers), weakness, peripheral neuropathy,
      Raynaud's phenomenon, sicca syndrome, membranoproliferative glomerulonephritis,
      and arthralgia and seldom arthritis. In patients with mixed cryoglobulinemia,
      prevalence of anti-hepatitis C virus (HCV) antibodies and/or HCV RNA, detected by
      polymerase chain reaction (PCR), is reported to be up to 90%, indicating a
      significant role of HCV in the development of this condition. The goals of
      therapy for mixed cryoglobulinemia include immunoglobulin level reduction and
      antigen elimination. CryoVas not associated with HCV infection should be treated
      according to treatment recommendations for small-vessel vasculitides. CryoVas
      associated with chronic HCV infection should be treated with antivirals along
      with immunosuppressive drugs, with or without plasmapheresis, depending on
      disease severity and organ involvement. Patients who do not respond to first-line
      therapy may achieve remission when treatment with rituximab is started as second
      line therapy. In HCV-related CryoVas, antiviral therapy should be given along
      with rituximab in order to achieve complete or partial remission. Moreover,
      rituximab has proven to be a glucocorticoid-sparing medication. Other potential
      therapies for refractory CryoVas include mycophenolate mofetil and belimumab,
      while tumor necrosis factor (TNF) inhibitors are not effective.

PMID- 28507448
TI  - Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia,
      inflammatory bowel disease and autoimmune disorders: influence on treatment
      response.
AB  - The thiopurine S-methyltransferase (TPMT) gene encodes for the TPMT enzyme that
      plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms
      in this gene can affect the activity of the TPMT enzyme and have been correlated
      with variability in response to treatment with thiopurines. Advances in the
      pharmacogenetics of TPMT allowed the development of dosing recommendations and
      treatment strategies to optimize and individualize prescribing thiopurine in an
      attempt to enhance treatment efficacy while minimizing toxicity. The influence of
      genetic polymorphisms in the TPMT gene on clinical outcome has been well
      documented and replicated in many studies. In this review, we provide an overview
      of the evolution, results, conclusions and recommendations of selected studies
      that investigated the influence of TPMT pharmacogenetics on thiopurine treatment
      in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune
      disorders. We focus mainly on prospective studies that explored the impact of
      individualized TPMT-based dosing of thiopurines on clinical response. Together,
      these studies demonstrate the importance of preemptive TPMT genetic screening and
      subsequent dose adjustment in mitigating the toxicity associated with thiopurine
      treatment while maintaining treatment efficacy and favorable long-term outcomes.
      In addition, we briefly address the cost-effectiveness of this pharmacogenetics
      approach and its impact on clinical practice as well as the importance of recent
      breakthrough advances in sequencing and genotyping techniques in refining the
      TPMT genetic screening process.

PMID- 28507450
TI  - Patient safety attitudes of pharmacy students in an Ethiopian university: a cross
      sectional study.
AB  - INTRODUCTION: Patient safety is a major health care concern and is being included
      in an undergraduate curriculum as it plays a major role in lessening harm.
      Therefore, we aim to assess the attitude of pharmacy students toward patient
      safety. METHODS: A cross-sectional study using a self-administered questionnaire
      containing 21 items was conducted at the University of Gondar among fourth and
      fifth year students. Data analysis was performed to calculate mean, standard
      deviation, percentages, and logistic regressions using SPSS software version 22
      (IBM Corporation, Armonk, NY, USA). Statistical significance was set at P<0.05.
      RESULTS: A total of 83 pharmacy students (fourth year groups=50, fifth year
      groups=33) participated in the study with response rate of 92%. Majority of the
      students 70/83 (84.33%) had the overall positive attitude of patient safety. Most
      of the respondents (80.7%) agree or strongly agree that after an error occurs, an
      effective strategy is to work hard to be more careful. Most of them (79.6%)
      believe that pharmacists should routinely spend part of their professional time
      working to improve patient care. About half (48.2%) of pharmacy students disagree
      or strongly disagree that pharmacists should discuss and report errors to an
      affected patient and their family even if the patient is not harmed. No
      significant association between the attitude of pharmacy students toward patient
      safety and their age, sex and year of study was found. CONCLUSION: Pharmacy
      students have the overall good attitude to patient safety. However, they claimed
      the culture and attitude within the pharmacy workplace lacked for patient safety.
      Moreover, standardized patient safety course should be considered in the
      curriculum for junior pharmacy students to improve their attitude toward patient
      safety.

PMID- 28507449
TI  - Perirenal fat stranding is not a powerful diagnostic tool for acute
      pyelonephritis.
AB  - PURPOSE: Pyelonephritis, an upper urinary tract infection, is a serious infection
      that often requires hospitalization. However, the accurate diagnosis of acute
      pyelonephritis can be difficult, especially among older individuals who can
      present with unusual symptoms. Imaging with computed tomography (CT) is not
      unusual in the diagnosis of pyelonephritis, with some clinicians regarding
      perirenal fat stranding (PFS) as a characteristic finding. However, the
      sensitivity and specificity of PFS in diagnosing pyelonephritis are currently
      unknown. We therefore sought to clarify the relevance of PFS in diagnosing acute
      pyelonephritis. PATIENTS AND METHODS: We conducted a case-controlled
      retrospective analysis of medical records. The pyelonephritis group included 89
      patients who had been diagnosed with acute pyelonephritis, while the control
      group included 319 patients who had undergone percutaneous renal biopsy. CT
      findings were available for both groups. The frequency of PFS and its sensitivity
      and specificity for the diagnosis of acute pyelonephritis were investigated.
      RESULTS: The mean ages of the pyelonephritis and control groups were 74+/-15
      years and 63+/-16 years, respectively. A total of 28% of men were in the
      pyelonephritis group vs 61% of men in the control group. The frequency of PFS was
      72% in the pyelonephritis group vs 39% in the control group. Age and renal
      dysfunction were associated with an increased frequency of PFS. After adjusting
      for age, sex, and renal function using a propensity score analysis, the
      sensitivity, specificity, and positive likelihood ratio of PFS for diagnosing
      acute pyelonephritis were 72%, 58%, and 1.7, respectively. CONCLUSION: The
      presence of PFS was not useful in diagnosing acute pyelonephritis.

PMID- 28507452
TI  - Consulted ethical problems of clinical nursing practice: perspective of faculty
      members in Japan.
AB  - BACKGROUND: There are several studies that have targeted student nurses, but few
      have clarified the details pertaining to the specific ethical problems in
      clinical practice with the viewpoint of the nursing faculty. This study was to
      investigate the ethical problems in clinical practice reported by student nurses
      to Japanese nursing faculty members for the purpose of improving ethics education
      in clinical practice. METHOD: The subjects comprised 705 nursing faculty members
      (we sent three questionnaires to one university) who managed clinical practice
      education at 235 Japanese nursing universities. We performed a simple tabulation
      of the four items shown in the study design. 1) the details of student nurse
      consultations regarding ethics in clinical practice (involving the students
      themselves, nurses, care workers, clinical instructors, and nursing faculty
      members); 2) the methods of ethics education in clinical practice; 3) the
      difficulties experienced by the nursing faculty members who received the
      consultations; and 4) the relationship between clinical practice and lectures on
      ethics. Furthermore, the analysis was based on the idea of ethical principles,
      respect for persons, beneficence, and justice. RESULTS: The response rate was 28%
      (198 questionnaires). The nursing faculty members were consulted for various
      problems by student nurses. The details of these consultations were characterized
      by the principles of respect for patient by nurses, the principles of benevolence
      by faculty and clinical instructors, and the principle of justice pertaining to
      evaluations. The results indicate that there is an awareness among the nursing
      faculty regarding the necessity of some sort of ethics education at clinical
      settings. Moreover, based on the nature of the contents of the consultations
      regarding the hospital and staff, it was evident that the nursing faculty
      struggled in providing responses. More than half of subjects exhibited an
      awareness of the relationship between the classroom lectures on ethics and
      clinical practice. CONCLUSION: The results suggest the need for analyzing the
      ethical viewpoints of student nurses, prior learning, and collaboration with
      related courses as part of ethics education in clinical practice.

PMID- 28507453
TI  - Erratum to: Suppression of Spry4 enhances cancer stem cell properties of human
      MDA-MB-231 breast carcinoma cells.
AB  - [This corrects the article DOI: 10.1186/s12935-016-0292-7.].

PMID- 28507454
TI  - Hypoxia and TGF-beta1 induced PLOD2 expression improve the migration and invasion
      of cervical cancer cells by promoting epithelial-to-mesenchymal transition (EMT)
      and focal adhesion formation.
AB  - BACKGROUND: Intra-tumoral hypoxia and increases in extracellular level of
      transforming growth factor beta1 (TGF-beta1), which are common findings in
      cancer, are associated with an increased risk of metastasis and mortality.
      Moreover, metastasis is the leading cause of death of patients with cervical
      cancer. PLOD2 is an intracellular enzyme required for the biogenesis of collagen
      and its expression can be induced by hypoxia and TGF-beta1. Specifically, PLOD2
      is up-regulated in several types of cancer, including cervical cancer, and is
      associated with cancer metastasis. Thus, in this research, we aimed to
      investigate the role of PLOD2 in the motility of cervical cancer cells and to
      show the molecular mechanism underlying this effect. METHODS: siRNA was used to
      knockdown PLOD2 in the cervical cancer cell lines HeLa and SiHa. The ability of
      cells to migrate and invade, their adhesion to type I collagen, and their
      capacity for epithelial-to-mesenchymal transition (EpsilonMUTau) and focal
      adhesion formation were analyzed. Gene expression changes were validated by qRT
      PCR, Western blotting and Immunocytochemistry. The morphological status of cells
      was examined using phalloidin staining. Differences in PLOD2 expression among
      patients with cervical cancer were identified by referring to public databases,
      including Oncomine and TCGA. RESULTS: Hypoxia and TGF-beta1 enhanced the
      expression of PLOD2 in HeLa and SiHa cells, and knockdown of PLOD2 inhibited cell
      motility and EMT. Moreover, the depletion of PLOD2 attenuated hypoxia-mediated
      cell migration and invasion and inhibited TGF-beta1-induced phenotypic EMT-like
      changes by preventing beta-catenin from entering the nucleus. In addition, PLOD2
      depletion decreased cell adhesion to extracellular collagen by inhibiting the
      formation of focal adhesions. Moreover, a database analysis showed that PLOD2
      expression is associated with human cervical cancer progression. CONCLUSIONS:
      Overall, our results indicated that hypoxia- and TGF-beta1-induced PLOD2
      expression promotes the migratory, invasive and adhesive capacities of cervical
      cancer cells by participating in TGF-beta1 induced EMT and the formation of focal
      adhesions.

PMID- 28507455
TI  - Neoadjuvant chemoradiotherapy of the rectal carcinoma - The correlation between
      the findings on the restaging multiparametric 3T MRI scanning and the surgical
      findings.
AB  - AIM: To figure out how to correlate the findings on functional MRI and carried
      out after neoadjuvant CRT of rectal carcinoma with final histology after surgery.
      BACKGROUND: Neoadjuvant CRT is the standard treatment of locally advanced rectal
      carcinoma. Its use leads to the downstaging of the disease and in 15-42% of
      patients even to the detection of pCR after TME. The use of functional MRI
      improves the sensitivity and specificity of pCR detection up to 52-64% and 89
      98%, respectively. MATERIALS AND METHODS: Between January 2013 and June 2016, 67
      patients suffering from histologically proven locally advanced rectal cancer
      underwent neoadjuvant RT or CRT. We selected for further investigation only
      patients (33 patients) who underwent pelvic staging and restaging using
      multiparametric imaging on 3T MRI scanner. We compared the findings on functional
      MRI after neoadjuvant CRT with final histology after surgery. RESULTS: In 15
      patients pathologic staging of primary tumor differed from expected staging
      assessed according to preoperative MRI. In 5 patients pathologic complete
      remission was achieved. In none of these 5 patients pCR was predicted using
      preoperative MRI. Sensitivity and specificity of MRI in predicting pCR were 0%
      and 96%. Accuracy of MRI in predicting pT and pN was 79% and 74%. CONCLUSIONS: We
      have verified that the use of neoadjuvant CRT in the treatment of locally
      advanced rectal carcinoma leads to a possible achievement of pCR. But in our
      group of patients this was not predictable nor was it with the use of
      multiparametric 3T MRI.

PMID- 28507458
TI  - Effect of tumor amplitude and frequency on 4D modeling of Vero4DRT system.
AB  - BACKGROUND: An important issue in indirect dynamic tumor tracking with the
      Vero4DRT system is the accuracy of the model predictions of the internal target
      position based on surrogate infrared (IR) marker measurement. We investigated the
      predictive uncertainty of 4D modeling using an external IR marker, focusing on
      the effect of the target and surrogate amplitudes and periods. METHODS: A
      programmable respiratory motion table was used to simulate breathing induced
      organ motion. Sinusoidal motion sequences were produced by a dynamic phantom with
      different amplitudes and periods. To investigate the 4D modeling error, the
      following amplitudes (peak-to-peak: 10-40 mm) and periods (2-8 s) were
      considered. The 95th percentile 4D modeling error (4D-E95%) between the detected
      and predicted target position (MU + 2SD) was calculated to investigate the 4D
      modeling error. RESULTS: 4D-E95% was linearly related to the target motion
      amplitude with a coefficient of determination R2 = 0.99 and ranged from 0.21 to
      0.88 mm. The 4D modeling error ranged from 1.49 to 0.14 mm and gradually
      decreased with increasing target motion period. CONCLUSIONS: We analyzed the
      predictive error in 4D modeling and the error due to the amplitude and period of
      target. 4D modeling error substantially increased with increasing amplitude and
      decreasing period of the target motion.

PMID- 28507456
TI  - Adjuvant intraoperative radiotherapy for selected breast cancers in previously
      irradiated women: Evidence for excellent feasibility and favorable outcomes.
AB  - BACKGROUND: The present report provides preliminary outcomes with intraoperative
      radiotherapy delivered to women with breast cancer included in a re-irradiation
      program. MATERIALS AND METHODS: From October 2010 to April 2014, thirty women
      were included in a re-irradiation protocol by exploiting IORT technique. The
      median time between the two irradiations was 10 years (range 3-50). All patients
      underwent conservative surgery, sentinel lymph node excision and IORT with
      electron beam delivered by a mobile linear accelerator. Primary endpoint was
      esthetic result and consequential/late toxicity; secondary endpoints were local
      control (LC), disease free survival (DFS) and overall survival (OS). RESULTS:
      With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1
      lost at follow up). Twenty-seven patients (90%) had presented breast cancer local
      relapse or a new primary cancer in the same breast after a previous conservative
      surgery plus radiation treatment; three patients (10%) had previously received
      irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent
      in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts
      (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC,
      DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION:
      Although we analyzed a small number of patients, our results are satisfactory and
      this approach is feasible even if it could not be considered the standard
      treatment. Further clinical trials exploring IORT are needed to identify possible
      subgroups of patients that might be suitable for this type of approach.

PMID- 28507457
TI  - Evaluating the performance of TG-43 protocol in esophageal HDR brachytherapy
      viewpoint to trachea inhomogeneity.
AB  - AIM: The aim of this study is to evaluate the effect of air within trachea on
      dose calculations of esophageal HDR brachytherapy treatment planning. BACKGROUND:
      Dose calculations in esophageal HDR brachytherapy treatment planning systems are
      greatly based on TG-43 protocol which in all materials are considered to be water
      equivalent. MATERIALS AND METHODS: A cylindrical PMMA phantom with a tube in the
      center (neck equivalent phantom) accompanied by Flexitron HDR brachytherapy
      system was used in this study. Brachytherapy applicators with various diameters
      were placed inside the esophageal tube and EDR2 film was used for dosimetry. The
      absorbed dose by reference point of esophageal HDR brachytherapy and anterior
      wall of trachea were measured and compared with those calculated by Flexiplan
      treatment planning system. RESULTS: Based on the performed statistical analysis
      (t-test) with 95% confidence level (t-value >1.96), there was a meaningful
      difference between the results of film dosimetry and treatment planning at all of
      the points understudy. CONCLUSION: The meaningful difference between the results
      of film dosimetry and treatment planning indicates that the trachea inhomogeneity
      has a considerable effect on dose calculations of Flexiplan treatment planning
      software featuring the TG-43 dose calculation algorithm. This mismatch can affect
      the accuracy of performed treatment plan and irradiation.

PMID- 28507459
TI  - Spironolactone ameliorates the cardiovascular toxicity induced by concomitant
      trastuzumab and thoracic radiotherapy.
AB  - AIM: We aimed to evaluate impact of spironolactone (S) on cardiovascular toxicity
      of concomitant use of radiotherapy (RT) and trastuzumab (T). BACKGROUND: S, an
      aldosterone receptor antagonist, is known to ameliorate the cardiac damage. S
      ameliorates anthracycline -induced cardiotoxicity, there is no data regarding to
      effect of S on both T and radiation-induced cardiotoxicity. MATERIALS/METHODS:
      Eighty rats were divided into eight groups: group (G) 1 was defined as control
      group. G2, G3 and G4 were RT, S and T groups respectively. G5, G6, G7 and G8 were
      RT + T, T + S, RT + S and RT + T + S groups respectively. Rats were sacrificed at
      6th hour; 21st and 100th days after RT. Heart and thoracic aorta samples were
      taken for microscopical examination. RESULTS: Cardiac inflammation and fibrosis
      scores and; TGF-beta expression were not significantly different within study
      groups at 6th hour and 21st days of RT. By 100th days of RT fibrosis scores and
      TGF-beta expression in cardiac samples were significantly different between study
      groups (p values were 0.004 and 0.002 respectively). Pair-wise comparisons
      revealed that both cardiac fibrosis scores and TGF-beta expression levels were
      higher in G5 when compared to G8 (p values were 0.046 and 0.028 respectively).
      Moreover the TGF-beta expression was higher in G5 when compared to G2 (p =
      0.046). We could not demonstrate any significant differences with respect to
      inflammation, fibrosis and TGF-beta expression in thoracic aorta samples between
      study groups. CONCLUSIONS: Although S had a protective effect on cardiac tissue
      it had no protective effect on thoracic aorta when administered with RT + T.

PMID- 28507460
TI  - Validation of the liver mean dose in terms of the biological effective dose for
      the prevention of radiation-induced liver damage.
AB  - AIM: The purpose of this study was to determine the optimal mean liver
      biologically effective dose (BED) to prevent radiation-induced liver disease
      (RILD) in stereotactic body radiation therapy (SBRT). BACKGROUND: The actual mean
      doses appropriate for liver irradiation in modern radiotherapy techniques have
      not been adequately investigated, although SBRT is sometimes alternatively
      performed using fractionated regimens. MATERIALS AND METHODS: SBRT treatment
      plans for liver tumors in 50 patients were analyzed. All distributions of the
      physical doses were transformed to BED2 using the linear-quadratic model. The
      relationship between physical doses and the BED2 for the liver were then
      analyzed, as was the relationship between the mean BED2 for the liver and the
      planning target volume (PTV). RESULTS: A significantly positive correlation was
      observed between the mean physical dose for the background liver and the mean
      BED2 for the whole liver (P < 0.0001, r = 0.9558). Using the LQ model, a mean
      BED2 of 73 and 16 Gy for the whole liver corresponded to the hepatic tolerable
      mean physical dose of 21 and 6 Gy for Child-Pugh A- and B-classified patients,
      respectively. Additionally, the PTV values were positively correlated with the
      BEDs for the whole liver (P < 0.0001, r = 0.8600), and the background liver (P <
      0.0001, r = 0.7854). CONCLUSION: A mean BED2 of 73 and 16 Gy for the whole liver
      appeared appropriate to prevent RILD in patients with Child-Pugh classes A and B,
      respectively. The mean BED2 for the liver correlated well with the PTV.

PMID- 28507461
TI  - Washed Away; How Not to Lose Your RNA during Isolation.
AB  - Cryptosporidium oocysts have extremely robust walls that protect the parasite
      against environmental pressures. Analyses must be sensitive to detect the few
      organisms (if any) present in environmental samples. After a series of negative
      nucleic acid amplification results on spiked samples, following a standard RNA
      isolation protocol, it seemed probable that oocyst RNA had been lost in the
      washing steps of the isolation protocol. By reducing both the volume of wash
      buffer and the number of washing steps, positive results could be re-established.
      Insufficient washing, however, seemed to prevent downstream analysis, probably
      because of inhibitory substances remaining in the RNA isolate. Nucleic acid
      isolation protocols for low numbers of "difficult" organisms should be adapted,
      according to the material to optimize the balance between removal of inhibitors
      and retention of target, thereby improving the performance of the technique.

PMID- 28507462
TI  - Comparative Analysis of Non-viral Transfection Methods in Mouse Embryonic
      Fibroblast Cells.
AB  - Mouse embryonic fibroblast (MEF) cells are an important in vitro model for
      developmental biology, disease, and reprogramming studies. However, as with other
      primary cells, they are challenging to transfect. Although viral gene-delivery
      methods achieve high gene-delivery efficiency, challenges with cell mutagenesis
      and safety among others have led to the use and improvement of non-viral gene
      delivery methods in MEF cells. Despite the importance of gene delivery in MEF
      cells, there is limited comparison of method/reagent efficacy. In this study, we
      compared the effectiveness of different gene-delivery methods and several
      reagents currently available in MEF cells by introducing a plasmid containing
      enhanced green fluorescent protein (EGFP). We analyze transfection efficiency by
      EGFP fluorescence. Our results suggest that two gene-delivery methods
      electroporation and magnetofection in combination with a lipid reagent, are the
      most efficient transfection methods in MEF cells. This study provides a
      foundation for the selection of transfection methods or reagents when using MEF
      cells.

PMID- 28507464
TI  - Chemical composition and biological activities of Salvia officinalis essential
      oil from Tunisia.
AB  - The aim of this study is to evaluate the chemical composition, antioxidant,
      antimicrobial, insecticidal and allelopathic activities of Tunisia Salvia
      officinalis essential oil (SoEO). The SoEO was characterized by the presence of
      49 components with camphor (25.14 %), alpha-thujone (18.83 %), 1,8-cineole (14.14
      %), viridiflorol (7.98 %), beta-thujone (4.46 %) and beta-caryophyllene (3.30 %)
      as the major components, determined by gas chromatography-mass spectrometry. The
      level of antioxidant activity, determined by complementary tests, namely 2,2
      diphenyl-1-picrylhydrazyl radical-scavenging (IC50= 6.7 mg/mL), linoleic acid
      peroxidation (IC50= 9.6 mg/mL) and ferric reducing assays (IC50= 28.4 mg/mL), was
      relatively moderate. The SoEO was also screened for its antimicrobial activity.
      Good to moderate inhibitions were recorded for most of tested microorganisms. It
      also exhibited important insecticidal activity against Spodoptera littoralis
      larvae and Tribolium castaneum adults with LC50 values of 55.99 and 97.43 ul/L
      air, respectively. The effect of the SoEO on seeds germination and growth showed
      different activities against radical and hypocotyl elongation of the tested
      species. These results suggest the potential use of the SoEO as natural
      antimicrobial preservative in cosmetic, pharmaceutical industry and in pest
      management.

PMID- 28507463
TI  - Radiotherapy-Induced Skin Reactions Induce Fibrosis Mediated by TGF-beta1
      Cytokine.
AB  - PURPOSE: This study aimed to investigate radiation-induced lesions on the skin in
      an experimental animal model. Methods and Materials: Cutaneous wounds were
      induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose
      rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin
      was observed 5, 10, and 25 days (D) after ionizing radiation exposition. RESULTS:
      Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60
      Gy groups, and a progressive increase of transforming growth factor beta1 is
      associated with this process. It could also be noted a mischaracterization of
      collagen fibers at the high-dose groups. CONCLUSION: It was observed that the
      lesions caused by ionizing radiation in rats were very similar to radiodermatitis
      in patients under radiotherapy treatment. ADVANCES IN KNOWLEDGE: This study is
      important to develop strategies to prevent radiation-induced skin reactions.

PMID- 28507466
TI  - High level of miR-196b at newly diagnosed pediatric acute myeloid leukemia
      predicts a poor outcome.
AB  - Differential expression of microRNAs (miRNAs) has been implicated in
      leukemogenesis. We investigate the expression pattern of miR-196b. Using
      quantitative real-time PCR (qRT-PCR), we detected the expression of miR-196b and
      its correlated genes (SMC1A/MLH1) in initial pediatric AML. A significant
      association was observed between overexpression of miR-196b and inferior overall
      survival of pediatric AML (Log Rank P<0.0001). AML M4/5 subtype, high white blood
      cell (WBC) count at presentation, MLL rearrangement, or FLT3-ITD mutation at
      diagnosis and non-remission group after the first induction chemotherapy
      possessed higher miR-196b expression. Furthermore, a positive relationship was
      found between the expression of miR-196b and SMC1A/MLH1 (Spearman's r=0.37 and
      0.44, P=0.001 and <0.0001, respectively). Taken together, these findings suggest
      that differentially high expression of miR-196b in diagnostic marrow samples of
      pediatric AML is associated with unfavorable outcome, and miR-196b potentially
      can be a novel biomarker for the diagnosis, prognosis and treatment in pediatric
      AML.

PMID- 28507467
TI  - Preparation and characterization of beta-glucan particles containing a payload of
      nanoembedded rifabutin for enhanced targeted delivery to macrophages.
AB  - beta-glucan particles (GP) are polymeric carbohydrates, mainly found as
      components of cell wall fungi, yeast, bacteria and also in cereals such as barley
      and oat, and have been recently shown to have application in macrophage-targeted
      drug delivery. The aim of this study was to prepare and characterize GP
      containing a large payload of Rifabutin (RB), an anti-tuberculosis drug effective
      against MDR-TB at lower MIC than Rifampicin. GP were prepared from yeast cells by
      acidic and alkaline extraction were either spray dried or lyophilized, prior to
      RB loading and alginate sealing. The FTIR and 13C-NMR spectra of the GP confirmed
      a beta-(1->3) linked glucan structure, with a triple-helical conformation. The
      spray dried GP exhibited better characteristics in terms of uniformity, size
      range (2.9 to 6.1 um) and more than 75 % particles were below 3.5 MUm. The RP
      HPLC analysis of spray dried GP revealed drug entrapment and drug loading up to
      81.46 +/- 4.9 % and ~40.5 +/- 1.9 %, respectively, as compared to those dried by
      lyophilization. Electron microscopy showed nearly spherical and porous nature of
      GP, and the presence of drug 'nanoprecipitates' filling the pore spaces. The
      formulation showed adequate thermal stability for pharmaceutical application. The
      particles were readily phagocytosed by macrophage(s) within 5 min of exposure.
      Drug release occurred in a sustained manner via diffusion, as the release
      kinetics best fit for drug release was obtained using Higuchi's equation. Thus,
      the spray dried GP-based-formulation technology holds promise for enhanced
      targeted delivery of anti-TB drug(s) to macrophage within a therapeutic window
      for the clearance of intracellular bacteria.

PMID- 28507468
TI  - Paradoxical effect of minocycline on established neuropathic pain in rat.
AB  - Neuropathic pain occurs after peripheral nerve damage, inflammation or infection.
      In this situation, microglial cells become activated and play a key role in
      producing pain. Minocycline (microglia inhibitor), was reported to reduce pain
      when used preventively. However, it seems that, when used after nerve injury,
      results in its pain reducing effects are different. In this regard, to assess the
      pain reducing differences of minocycline, neuropathic pain was induced by the
      ligation of the sciatic nerve in the rat which is recognized as chronic
      constriction injury (CCI) and minocycline was administered before and after
      sciatic nerve injury. Wistar male rats (200-250 g, n=6) were used in these
      experiments. Rats were distributed in various groups: vehicle-treated CCI
      (control), sham-operated and minocycline-treated CCI groups. In the first part of
      the experiment (pre-injury study), minocycline (10, 20, 30 and 40 mg/kg,) was
      injected one hour before surgery and then daily for two weeks. In the second part
      (post injury study), minocycline was administered: 1: at day one after nerve
      damage once a day to day 14, 2: at day seven after surgery and continued daily
      until day 14. Analgesimeter for thermal hyperalgesia and von Frey hairs for
      mechanical allodynia were used to evaluate pain behavior. Thermal hyperalgesia
      and mechanical allodynia were attenuated significantly, when minocycline used
      before surgery, while it was not able to reduce pain behavior administered after
      surgery. It seems that, in spite of what some previous studies have reported,
      here, minocycline is not able to attenuate established neuropathic pain.

PMID- 28507465
TI  - Distribution of polymorphic variants of CYP2A6 and their involvement in nicotine
      addiction.
AB  - Tobacco consumption has become a major public health issue, which has motivated
      studies to identify and understand the biological processes involved in the
      smoking behavior for prevention and smoking cessation treatments. CYP2A6 has been
      identified as the main gene that codifies the enzyme that metabolizes nicotine.
      Many alleles have been identified after the discovery of CYP2A6, suggesting a
      wide interethnic variability and a diverse smoking behavior of the allele
      carrying individuals. The main purpose of this review is to update and highlight
      the effects of the CYP2A6 gene variability related to tobacco consumption
      reported from diverse human populations. The review further aims to consider
      CYP2A6 in future studies as a possible genetic marker for the prevention and
      treatment of nicotine addiction. Therefore, we analyzed several population
      studies and their importance at addressing and characterizing a population using
      specific parameters. Our efforts may contribute to a personalized system for
      detecting, preventing and treating populations at a higher risk of smoking to
      avoid diseases related to tobacco consumption.

PMID- 28507469
TI  - Lungs deposition and pharmacokinetic study of submicron budesonide particles in
      Wistar rats intended for immediate effect in asthma.
AB  - The purpose of the present investigation was to study the aerosolization, lungs
      deposition and pharmacokinetic study of inhalable submicron particles of
      budesonide in male Wistar rats. Submicron particles were prepared by antisolvent
      nanoprecipitation method and freeze-dried to obtain free flowing powder. The
      freeze-drying process yielded dry powder with desirable aerodynamic properties
      for inhalation therapy. An in-house model inhaler was designed to deliver
      medicine to lungs, optimized at dose level of 10 mg for 30 sec of fluidization.
      The in vitro aerosolization study demonstrates that submicron particles dissolve
      faster with improved aerosolization effect as compared to micronized budesonide.
      Both submicron and micron particles were compared for in vivo lungs deposition.
      The results showed that relatively high quantity of submicron particles reaches
      deep into the lungs as compared to micron particles. Most pronounced effect
      observed with submicron particles from pharmacokinetic parameters was the
      enhancement in peak plasma concentration (Cmax) by 28.85 %, and increase in area
      under concentration curve (AUC0-8h) by 30.33 % compared to micron sized
      particles. The results suggested that developed submicronized formulation of
      budesonide can be used for pulmonary drug delivery for high deposition to deep
      lungs tissues.

PMID- 28507470
TI  - Evaluating the relationship of blood pressure, plasma angiotensin peptides and
      aldosterone with cognitive functions in patients with hypertension.
AB  - Renin Angiotensin Aldosterone System (RAAS) plays an important role in the
      development of hypertension. On the other hand, hypertension is a well-known and
      independent risk factor for cognitive impairment. The aim of the present study
      was to evaluate the relationship of blood pressure control, plasma angiotensin
      peptides and aldosterone with cognitive functions. Forty-one patients who were
      under treatment with the same antihypertensive medications for at least three
      months were included in the study. Plasma angiotensin II, angiotensin 1-7,
      angiotensin IV, and aldosterone concentrations were analyzed using an enzyme
      linked immunosorbent assay (ELISA). Standardized Mini Mental State Examination
      (SMMSE) was used to evaluate cognitive functions. When the participants were
      grouped according to their SMMSE scores (cut-off value: 26 points), we determined
      significant differences between systolic blood pressure (SBP) levels, diastolic
      blood pressure levels, plasma angiotensin II and angiotensin 1-7 concentrations
      of the groups. When the participants were stratified according to their SBP
      levels (cut-off value: 140 mm Hg), we found significant differences in SMMSE
      scores and plasma angiotensin IV concentrations of the groups. A negative
      correlation between SBP and SMMSE scores and strong linear correlations among
      angiotensin peptides levels were determined. The relationship found between SBP
      and SMMSE in the present study was compatible with the literature. Our 33
      patients were using at least one angiotensin II receptor blocker (ARB). Regarding
      AT1 receptor blockage, the significant association between higher SMMSE scores
      and increased angiotensin peptides may support a finding that ARBs prevent
      dementia and improve cognitive function. Further larger studies are needed to
      confirm and prove the relation of RAAS biochemical parameters with cognitive
      function.

PMID- 28507471
TI  - Seroepidemiological study of Toxoplasma gondii infection in a population of
      Iranian epileptic patients.
AB  - Epilepsy is one of the most common neurologic disorders. Underlying cause of
      epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an
      intracellular parasite which is capable of forming tissue cysts in brain of
      chronically infected hosts including humans. Some epidemiological studies
      suggested an association between toxoplasmosis and acquisition of epilepsy. In
      this study we determined seroprevalence of latent Toxoplasma infection in a
      population of Iranian epileptic patients. Participants were classified in three
      groups as Iranian epileptic patients (IEP, n = 414), non-epileptic patients who
      had other neurologic disorders (NEP, n = 150), and healthy people without any
      neurologic disorders (HP, n = 63). The presence of anti-Toxoplasma IgG antibodies
      and IgG titer in the sera were determined by ELISA method. Anti-T. gondii IgG
      seroprevalence obtained 35.3 %, 34.7 % and 38.1 % in IEP, NEP and HP,
      respectively. The seroprevalence rate was not significantly different among the
      three groups (P = 0.88). Anti-T. gondii IgG titer was 55.7 +/- 78, 52.4 +/- 74
      and 69.7 +/- 92 IU/ml in IEP, NEP and HP, respectively. There was not any
      statistically significant difference in the antibody titer between the study
      groups (P = 0.32). The rate of T. gondii infection in epileptic patients was not
      higher than non-epileptic patients and healthy people in the Iranian population.

PMID- 28507472
TI  - Schisandrae Fructus ethanol extract ameliorates inflammatory responses and
      articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in
      rats.
AB  - Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely
      used in traditional medicine for the treatment of a number of chronic diseases.
      Although, Schisandrae Fructus was recently reported to attenuate the interleukin
      (IL)-1beta-induced inflammatory response in chondrocytes in vitro, its protective
      and therapeutic potential against osteoarthritis (OA) in an animal model remains
      unclear. Therefore, we investigated the effects of the ethanol extract of
      Schisandrae Fructus (SF) on inflammatory responses and cartilage degradation in a
      monosodium iodoacetate (MIA)-induced OA rat model. Our results demonstrated that
      administration with SF had a tendency to attenuate MIA-induced damage of
      articular cartilage as determined by a histological grade of OA. SF significantly
      suppressed the production of pro-inflammatory cytokines such as interleukin (IL)
      1beta, IL-6, and tumor necrosis factor-alpha in MIA-induced OA rats. SF also
      effectively inhibited expression of inducible nitric oxide (NO) synthase and
      cyclooxygenase-2, thereby inhibiting the release of NO and prostaglandin E2. In
      addition, the elevated levels of matrix metalloproteinases-13 and two biomarkers
      for diagnosis and progression of OA, such as cartilage oligomeric matrix protein
      and C-telopeptide of type II collagen, were markedly ameliorated by SF
      administration. These findings indicate that SF could be a potential candidate
      for the treatment of OA.

PMID- 28507473
TI  - Effects of symbiotic and vitamin E supplementation on blood pressure, nitric
      oxide and inflammatory factors in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) has been suggested to be well
      correlated with altered blood pressure. This study was conducted to determine the
      effects of symbiotic and vitamin E supplementation on blood pressure and
      inflammatory indices of patients with NAFLD. This randomized, double-blind,
      placebo-controlled trial was performed among 60 NAFLD patients aged 25 to 64
      years old. Participants were randomly divided into four groups to receive a 400
      IU alpha-tocopherol and 2 * 108 CFU/g symbiotic supplement for 8 weeks. The
      anthropometric parameters, systolic blood pressure (SBP) and diastolic blood
      pressure (DBP), serum malondialdehyde (MDA), nitric oxide (NO) and tumor necrosis
      factor alpha (TNFalpha) were assessed at baseline and after 8 weeks of
      intervention. After 8 weeks of intervention, combined symbiotic and alpha
      tocopherol, symbiotic and alpha-tocopherol alone administration, compared with
      the placebo, resulted in significant decreases in SBP (-17.07+/-2.1, -16.07+/
      3.56, -1.73+/-2.25 and -1.55+/-3.01 mmHg, P=0.01), serum MDA (-1.19+/-0.5, 
      0.12+/-0.65, 0.14 +/- 0.64 and 0.16+/-0.34 nmol/mL, P<0.001), serum TNFalpha (
      15.62+/-13.93, -9.24+/-7.12, -11.44 +/- 15.47 and 3.01+/-1.71 pg/ml, P<0.001)
      concentrations. A significant decrease in serum AST (-11.36+/-4.52, -7.43+/-8.58,
      -5.93+/-6.61 and 2.5+/-5.75 MUmol/L, P <0.001), ALT (-12.79+/-3.65, -3.66+/-6.81,
      -6.54+/-7.66 and 4.16+/-3.43 MUmol/L, P <0.001) and ALP (-26.8+/-11.1, -4.56+/
      9.22, -14.48+/-12.22 and 5.19+/-2.64 MUmol/L, P <0.001) was seen. Variations in
      DBP and serum NO concentration were not significant. Alpha-tocopherol and
      symbiotic supplementation among patients with NAFLD resulted in decreased SBP,
      serum MDA, TNFalpha levels and enzymes liver; however, they did not affect DBP
      and serum NO concentration.

PMID- 28507474
TI  - Anacardium microcarpum extract and fractions protect against paraquat-induced
      toxicity in Drosophila melanogaster.
AB  - Anacardium microcarpum Ducke (Anacardiaceae) is a native species of Brazil used
      in folk medicine for the treatment of several illnesses although its antioxidant
      activity has been reported in vitro, there is no evidence of this effect in an in
      vivo model. Here, we investigated the potential protective effect of
      hydroalcoholic extract (AMHE), methanol (AMMF) and acetate (AMAF) fraction of A.
      microcarpum against paraquat toxicity on survivorship, locomotor performance,
      antioxidant enzymes activity and reactive species using Drosophila melanogaster.
      Flies were exposed to the extract or fractions (1 and 10 mg/ml) in the presence
      or absence of paraquat (5 mM) in sucrose solution for 72 h. In addition, total
      phenolic content of extract and fractions was evaluated as well as ABTS radical
      scavenging capacity. Our results demonstrated that AMAF presented higher content
      of phenols and ABTS chelating potential. Treatment of flies with the extract or
      fractions did not alter the survivorship, locomotor ability, and
      acetylcholinesterase (AchE) activity per se. Paraquat caused 85 % mortality of
      flies and 30 % increase in reactive species generation, which were significantly
      attenuated by AMHE and AMMF. AAMF increased catalase activity (from 66.77 +/-
      6.64 to 223.94 +/- 25.92 mU/mg of protein), while AMAF increased GST activity
      (from 477.76 +/- 92 to 770.19 +/- 147.92 mU/mg of protein) and catalase activity
      (from 66.77 +/- 6.64 to 220.54 +/- 26.63 mU/mg of protein). AMHE and AMMF were
      more effective in protecting against paraquat toxicity. Taken together, the data
      indicate the potential of this plant in acting as a protective and antioxidant
      agent in vivo.

PMID- 28507475
TI  - Macrophage migration inhibitory factor -173 G > C polymorphism and risk of
      tuberculosis: A meta-analysis.
AB  - The aim of the present meta-analysis was to find out the impact of MIF -173 G > C
      polymorphism on risk of tuberculosis (TB). We conducted a search of case-control
      studies on the associations of -173 G > C variant of MIF with susceptibility to
      tuberculosis in PubMed, ISI Web of Science, and Scopus. We extracted the data
      from eligible studies and achieved a meta-analysis to examine the relationship
      between MIF -173 G > C polymorphism and the risk of TB. Odds ratios (ORs) with
      the corresponding 95 % confidence intervals (CIs) were pooled to find out the
      impact of MIF -173G > C promoter polymorphism on TB risk. The pooled ORs were
      calculated for the codominant, dominant, recessive, and allelic model comparison.
      The findings revealed that MIF -173 G > C variant increased the risk of TB in
      codominant (OR = 1.54, 95 %CI = 1.26-1.88, p < 0.0001; CG vs GG), and dominant
      (OR = 1.62, 95 %CI = 1.33-1.96, p < 0.00001; GC+CC vs GG) inheritance models
      tested. The results suggested that the MIF -173 C allele significantly increased
      the risk of PTB (OR = 1.49, 95 %CI = 1.28-1.74, p < 0.00001). The findings of
      this meta-analysis propose that MIF -173 G > C variant is associated with the
      risk of TB. More case-control studies with well-designed in different ethnic
      groups and larger sample size are needed to confirm the findings.

PMID- 28507476
TI  - Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole: A
      single dose study in healthy human volunteers.
AB  - Based upon the known potential interaction between omeprazole (OMP) and
      clopidogrel (CLOP), the current study was designed to evaluate the effect of CLOP
      on disposition of OMP and its two major metabolites, 5-hydroxyomeprazole (5-OH
      OMP) and omeprazole sulfone (OMP-S) in healthy clinical subjects. A randomized,
      open label, 2-period, crossover study was designed. Twelve volunteers were
      selected, of whom eight were extensive metabolizers (EM) of CYP2C19 and 4 were
      poor metabolizers (PM). They received single dose of OMP either alone or in
      combination with CLOP (single dose) and samples were collected periodically to
      calculate various pharmacokinetic parameters. Changes in most of the
      pharmacokinetic parameters of OMP, 5-OH-OMP and OMP-S were insignificant (P ?
      0.05) both in EM and PM except for the maximum concentration (Cmax) of 5-OH-OMP
      and OMP-S in EM. The OMP Cmax and AUC0-infinity was increased both in EM and PM
      after concomitant administration of OMP with CLOP. The 5-OH-OMP Cmax was
      decreased in both EM and PM, demonstrating that CLOP inhibits hydroxylation of
      OMP. The OMP-S Cmax and AUC0-infinity were increased both in EM and PM showing
      that CLOP may induce sulfoxidation of OMP. It was concluded that CLOP may inhibit
      hydroxylation of OMP to a greater extent in EM than in PM, leading to higher OMP
      Cmax and AUC0-infinity. Furthermore, the sulfoxidation of OMP may also be induced
      by CLOP. So, it is suggested that both these drugs should be carefully prescribed
      together to avoid any harm to the patients. (Application number13/EC/Pharm. Ref
      number 12/Pharm).

PMID- 28507477
TI  - Enzymatic hydrolysate from velvet antler suppresses adipogenesis in 3T3-L1 cells
      and attenuates obesity in high-fat diet-fed mice.
AB  - The purpose of the current study was to investigate the potential anti-obesity
      activity of an enzymatic hydrolysate of velvet antler in inhibiting adipogenesis
      in 3T3-L1 cells and in high-fat diet (HFD)-fed obese mice. The enzymatic
      hydrolysate was prepared using the commercial food grade protease, Protamex. The
      velvet antler Protamex hydrolysate (VAPH) indicated profound inhibitory effects
      on adipogenesis dose-dependently by decreasing the accumulation of triglycerides
      and down-regulating expression levels of adipogenesis-related proteins
      C/EBPalpha, SREBP-1, and PPARgamma. In a mouse model of HFD-induced obesity, oral
      administration of VAPH (100 and 300 mg/kg for 13 weeks) significantly reduced the
      body weight gain that had resulted from the HFD. VAPH treatment also lowered the
      serum glucose and triglyceride levels, while increasing the HDL-C level.
      Furthermore, the treatment greatly reduced hepatic lipid droplet accumulation as
      well as the size of adipocytes. Current findings demonstrate that VAPH has
      profound anti-obesity effects and could be an effective candidate for preventing
      obesity and obesity-related chronic diseases.

PMID- 28507479
TI  - Knockdown of lncRNA-PANDAR suppresses the proliferation, cell cycle and promotes
      apoptosis in thyroid cancer cells.
AB  - Long non-coding RNAs (lncRNAs) have been found to show important regulatory roles
      in various human cancers. Lnc-RNA PANDAR is a novel identified lncRNA that was
      previously reported to show abnormal expression pattern in various cancers.
      However, little is known of its expression and biological function in thyroid
      cancer. Here, we used the quantitative real-time PCR (qRT-PCR) to determine the
      expression of PANDAR in 64 thyroid cancer tissues. We found that expression of
      PANDAR was up-regulated in thyroid cancer tissues compared with adjacent non
      tumor tissues. Functional assays in vitro demonstrated that knockdown of PANDAR
      could inhibit proliferation, cell cycle progression, induces the apoptosis,
      inhibit invasion of thyroid cancer cells. Thus, our study provides evidence that
      PANDAR may function as a potential target for treatment for patients with thyroid
      cancer.

PMID- 28507478
TI  - Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1
      FOXO1 pathway.
AB  - Sirtuin1 (SIRT1) and forkhead box transcription factor O subfamily 1 (FOXO1) play
      vital roles in the maintenance of hippocampal neuronal homeostasis during aging.
      Our previous study showed that melatonin, a hormone mainly secreted by the pineal
      gland, restored the impaired memory of aged mice. Age-related neuronal energy
      deficits contribute to the pathogenesis of several neurodegenerative disorders.
      An attempt has been made to determine whether the effect of melatonin is mediated
      through the SIRT1-FOXO1 pathways. The present results showed that aged mice (22
      months old) exhibited significantly downregulated SIRT1, FOXO1, and melatonin
      receptors MT1 and MT2 protein expression but upregulated tumor suppressor protein
      53 (p53), acetyl-p53 protein (Ac-p53), mouse double minute 2 homolog (MDM2),
      Dickkopf-1 (DKK1) protein expression in mouse hippocampus compared with the young
      group. Melatonin treatment (10 mg/kg, daily in drinking water for 6 months) in
      aged mice significantly attenuated the age-induced downregulation of SIRT1,
      FOXO1, MT1 and MT2 protein expression and attenuated the age-induced increase in
      p53, ac-p53, MDM2, and DKK1 protein and mRNA expression. Melatonin decreased p53
      and MDM2 expression, which led to a decrease in FOXO1 degradation. These present
      results suggest that melatonin may help the hippocampal neuronal homeostasis by
      increasing SIRT1, FOXO1 and melatonin receptors expression while decreasing DKK1
      expression in the aging hippocampus. DKK1 can be induced by the accumulation of
      amyloid beta (Abeta) which is the major hallmark of Alzheimer's disease.

PMID- 28507480
TI  - Electro-acupuncture promotes the proliferation of neural stem cells and the
      survival of neurons by downregulating miR-449a in rat with spinal cord injury.
AB  - The aim of this study is to investigate the mechanism of electro-acupuncture (EA)
      on the recovery of injured spinal cord. Rats were randomly divided into normal
      control, sham-operated, SCI, SCI+EA group and T10 segment spinal cord injury
      (SCI) rat model was established by the modified Allen's method. After 7 days, the
      mRNA and protein expression of Nestin, neuron specific nuclear protein (NeuN) and
      calcitonin gene related peptide (CGRP) were detected by real time RT-PCR, Western
      blot and immunohistochemistry respectively. The protein expression of cleaved
      caspase 3, Bax, Bcl-2, TNF-alpha and IL-1beta were also detected by Western blot.
      MicroRNA 449a (miR-449a) expression was also compared. Further, 12 SCI rats were
      randomly divided into EA and miR subgroups (EA + miR-449a agomir injection). The
      expression of Nestin, NeuN, CGRP, cleaved caspase 3, Bax, Bcl-2, TNF-alpha, IL
      1beta and miR-449a was compared. The direct interaction of miR-449a and CGRP mRNA
      was assessed by dual luciferase reporter assay. At day 7, compared with sham
      operated group, miR-449a expression in SCI group was significantly increased (P <
      0.05), and NeuN and CGRP mRNA and protein expression was markedly decreased (P <
      0.05), but protein levels of Nestin, cleaved caspase 3, TNF-alpha, IL-1beta and
      the ratio of Bax/Bcl-2 in SCI group were significantly increased (P < 0.05). The
      EA treatment significantly reduced miR-449a level and cleaved caspase 3, TNF
      alpha, IL-1beta level and the ratio of Bax/Bcl-2 (P < 0.01), but substantially
      increased Nestin, NeuN and CGRP expression (P < 0.05 or 0.01). High level of miR
      449a in miR subgroup was accompanied by decreased expression of Nestin, NeuN and
      CGRP and increased expression of cleaved caspase 3, TNF-alpha, IL-1beta and
      elevation of the ratio of Bax/Bcl-2 (P < 0.05), suggesting miR-449a inhibits the
      effects of EA on NSCs and neurons. Luciferase reporter assay showed that miR-449a
      bound to the 3' UTR of CGRP, and thereby regulated CGRP expression. In
      conclusion, EA promotes proliferation of neural stem cells and the survival of
      neurons by downregulation of miR-449a expression.

PMID- 28507481
TI  - Isolation and characterization of phthalates from Brevibacterium mcbrellneri that
      cause cytotoxicity and cell cycle arrest.
AB  - Bacteria belonging to the family Brevibacterieae are ubiquitous Gram positive
      organisms that are responsible for the feet odour and cheese aroma.
      Brevibacterium mcbrellneri is a relatively new member belonging to
      Brevibacterieae. In the current manuscript we discuss isolation of biologically
      active metabolites from Brevibacterium mcbrellneri. Two aromatic esters were
      isolated from Brevibacterium mcbrellneri by "Bioassay guided fractionation
      strategy" and identified as di-(2-ethylhexyl) phthalate and dibutyl phthalate by
      chemical characterization using biophysical techniques. The phthalate compounds
      show broad spectrum antibacterial activity and mosquito larvicidal activity.
      Mosquito larvicidal activity has been attributed to inhibition of
      acetylcholinesterase enzyme activity. These compounds were found to be cytotoxic
      in multiple cell lines causing cell cycle arrest in G1 phase.

PMID- 28507482
TI  - Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives.
AB  - Due to high relative blood flow the kidney is prone to drug-induced damage.
      Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug
      induced nephrotoxicity. In recent years gentamicin nephrotoxicity is
      significantly reduced by shifting to once daily dosage as well as by eliminating
      known risk factors. Application of gentamicin is still related to serious side
      effects which are reported more often compared to other antibiotics. Because
      gentamicin is still heavily used and is highly efficient in treating infections,
      it is important to find mechanisms to reduce its nephrotoxicity. This aim can
      only be achieved through better understanding of kidney metabolism of gentamicin.
      This problem has been extensively researched in the last 20 years. The
      experimental results have provided evidence for almost complete understanding of
      mechanisms responsible for gentamicin nephrotoxicity. We now have well described
      morphological, biochemical and functional changes in kidney due to gentamicin
      application. During the years, this model has become so popular that now it is
      used as an experimental model for nephrotoxicity per se. This situation can
      mislead an ordinary reader of scientific literature that we know everything about
      it and there is nothing new to discover here. But quite opposite is true. The
      precise and complete mechanism of gentamicin nephrotoxicity is still point of
      speculation and an unfinished story. With emerge of new and versatile technics in
      biomedicine we have an opportunity to reexamine old beliefs and discover new
      facts. This review focuses on current knowledge in this area and gives some
      future perspectives.

PMID- 28507484
TI  - Imaging and Analysis of Encapsulated Objects through Self-Assembled Electron and
      Optically Transparent Graphene Oxide Membranes.
AB  - We demonstrate a technique for facile encapsulation and adhesion of micro- and
      nano objects on arbitrary substrates, stencils, and micro structured surfaces by
      ultrathin graphene oxide membranes via a simple drop casting of graphene oxide
      solution. A self-assembled encapsulating membrane forms during the drying process
      at the liquid-air and liquid-solid interfaces and consists of a water-permeable
      quasi-2D network of overlapping graphene oxide flakes. Upon drying and
      interlocking between the flakes, the encapsulating coating around the object
      becomes mechanically robust, chemically protective, and yet highly transparent to
      electrons and photons in a wide energy range, enabling microscopic and
      spectroscopic access to encapsulated objects. The characteristic encapsulation
      scenarios were demonstrated on a set of representative inorganic and organic
      micro and nano-objects and microstructured surfaces. Different coating regimes
      can be achieved by controlling the pH of the supporting solution, and the
      hydrophobicity and morphology of interfaces. Several specific phenomena such as
      compression of encased objects by contracting membranes as well as hierarchical
      encapsulations were observed. Finally, electron as well as optical microscopy and
      analysis of encapsulated objects along with the membrane effect on the image
      contrast formation, and signal attenuation are discussed.

PMID- 28507483
TI  - Effects of hesperidin on formaldehyde-induced toxicity in pregnant rats.
AB  - This experimental study aimed to investigate the protective effect of a
      bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological
      and behavioral outcomes in pregnant rats and developmental aspects in their
      offspring. Female Wistar rats were subjected to perigestational exposure to FA (2
      mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os).
      Pregnant rats were weighed throughout gestation and tested in two behavioral
      paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and
      19 to evaluate the anxiety-like behavior and locomotive alterations. Another
      subset of rats was decapitated at GD19 to determine the hematological profile
      along with cortisol, 17beta-estradiol, and progesterone plasma levels.
      Reproductive and fetal measures and observations were also performed to check for
      developmental deformities. Significant body weight loss, hemato-immune decline,
      hormonal changes, anxiety and lethargy signs, locomotor disabilities,
      reproductive failure and fetal weight decrease were observed in FA-exposed rats.
      Treatment with HP alleviated the reproductive and fetal weight defects. Its
      behavioral benefits were only seen at GD1 and 10. This flavanone ameliorated some
      hematological parameters, decreased cortisol levels and increased 17beta
      estradiol rates. A potential preventive impact of HP was found against FA
      toxicity in pregnant rats.

PMID- 28507486
TI  - Melanin and lipofuscin as hallmarks of skin aging.
AB  - Discoloration are symptoms of skin aging. They are connected with presence of
      melanin and lipofuscin, whose excess and abnormal distribution in the skin cause
      dark spots to appear. Melanin is formed under the influence of tyrosinase during
      melanogenesis. Its content changes with age, which may be a result of menopause.
      Lipofuscin is another example of the age pigment. It is composed of proteins,
      lipids and carbohydrates. It is described as an age pigment because its content
      increases with age. The formation and accumulation of lipofuscin is inevitable
      and leads to cell and homeostasis dysfunction because it reduces the proteasome
      activity.

PMID- 28507485
TI  - The influence of dietary immunomodulatory factors on development of food allergy
      in children.
AB  - In the last few years many studies have been conducted on the role of dietary and
      environmental factors in the prevention of allergic diseases among children. Many
      studies have shown that the diet of pregnant women and children in their early
      postnatal life, rich in antioxidants, vitamin D, and fatty acids is beneficial as
      it reduces the risk of allergy in their future life. Moreover, there are many
      reports about the main role of gut microbiota and probiotics in the allergy
      prevention, what can indicate new ways of procedures in allergic diseases.

PMID- 28507488
TI  - Microbiological analysis of acute infections of the nail fold on the basis of
      bait thread test.
AB  - INTRODUCTION: An acute infection of the nail fold, called paronychia, is a common
      clinical problem. The basis for the implementation of the treatment is the result
      of microbiological examination. Due to the rapid and painful course of infection,
      usually an empirical antimicrobial treatment prior to obtaining microbiological
      test results is introduced. AIM: The microbial analysis of acute infections of
      the nail fold. MATERIAL AND METHODS: The study included 32 tests conducted on 31
      patients of the Department of Dermatology. Microbiological analysis was performed
      with the use of the so-called bait thread test. RESULTS: In 73% of analyzed cases
      microbiological examination revealed mixed microbiological flora. Most cultured
      microorganisms were: Enterococcus faecalis (14%), Staphylococcus aureus (12%),
      Candida albicans (9%), Enterobacter cloacae (8%), and Klebsiella pneumoniae (7%).
      Most cultured bacteria belonged to the families or genera of Enterobacteriaceae
      (36%), other cultured bacteria were staphylococci (26%), enterococci (16%),
      Candida species (14%), and Gram-negative non-fermenting bacilli (8%).
      CONCLUSIONS: The acute infection of the nail fold in the vast majority of cases
      is caused by mixed bacterial flora. A profile of isolated microorganisms suggests
      that the cause of the infection can be associated with neglect of hygiene.
      Fluoroquinolone and fusidic acid are recommended as the empirical therapy.
      Microbiological examination is the basis for the appropriate final treatment.

PMID- 28507487
TI  - Demographic characteristics, aetiology, and assessment of treatment options in
      leukocytoclastic vasculitis.
AB  - INTRODUCTION: Vasculitides are a heterogeneous group of diseases characterized by
      inflammation of the blood vessel walls. Etiological factors include infections,
      drugs, connective tissue diseases, and malignancies. AIM: To examine the
      demographic characteristics, etiological factors, and treatment options in 75
      patients with leukocytoclastic vasculitis. MATERIAL AND METHODS: The study
      included 75 patients diagnosed with leukocytoclastic vasculitis at our clinic.
      The patients' medical records were reviewed to determine their age, sex, presence
      of systemic symptoms, possible etiological factors, laboratory results, types of
      cutaneous lesions, locations of the lesions, treatment options, and disease
      course. RESULTS: There were 43 women and 32 men. Cutaneous lesions affected only
      the lower limbs in 60 of the 75 patients (80%) and usually presented as palpable
      purpura (64%, n = 48). Arthralgia (26.7%, n = 20) was the most frequent
      extracutaneous symptom. Of the patients with secondary vasculitis, the most
      common causes were infections and drugs. The mean age of the patients with Henoch
      Schonlein purpura was 26.8 years. There was no significant association between
      age and renal, gastrointestinal, or joint involvement. CONCLUSIONS: The most
      common form of vasculitis in our study was cutaneous leukocytoclastic vasculitis.
      In most of the patients it appeared to be idiopathic. Among drugs, antibiotics
      were the most common etiological factor. In 4 patients, the cutaneous
      leukocytoclastic vasculitis behaved like the paraneoplastic syndrome.

PMID- 28507489
TI  - Evaluation of the serum zinc level in patients with vitiligo.
AB  - INTRODUCTION: Vitiligo is an acquired, idiopathic disorder characterized by
      circumscribed depigmented macules and patches, which affects approximately 0.1-2%
      of the general population worldwide. Zinc is an essential trace element that is
      necessary for growth and development at all stages of life. Some studies have
      reported an association between serum zinc levels and vitiligo. AIM: To measure
      the serum zinc level in patients with vitiligo compared to healthy subjects.
      MATERIAL AND METHODS: One hundred patients with vitiligo and 100 healthy controls
      were referred to our clinic. The two groups were matched for age and sex. Atomic
      absorption spectrophotometry was used to measure serum zinc levels. The
      statistical analysis was performed using SPSS software. RESULTS: The mean serum
      level of zinc in vitiligo patients and controls was 80.11 +/-17.10 MUg/dl and
      96.10 +/-16.16 MUg/dl, respectively. The serum zinc level in patients with
      vitiligo was significantly lower than in healthy controls (p = 0.0001).
      CONCLUSIONS: The results of our study revealed a significant association between
      vitiligo and serum zinc levels. A relative decrease in the serum zinc level in
      vitiligo patients can highlight the role of zinc in the pathogenesis of vitiligo,
      and large-scale studies need to be conducted to confirm these findings and assess
      the effect of oral zinc supplements in patients with low zinc levels.

PMID- 28507490
TI  - Cognitive impairment in patients with severe psoriasis.
AB  - INTRODUCTION: Psoriasis is a chronic inflammatory skin disease, in which an
      important role is played by psychological factors. AIM: To evaluate the frontal
      cognitive functions in patients with psoriasis. MATERIAL AND METHODS: The study
      included 188 subjects (97 patients with psoriasis and 91 healthy controls). To
      assess the dorsolateral prefrontal cortex functions, the Trail Making Test and
      the Stroop test were applied. Severity of psoriasis was assessed by means of the
      PASI index. RESULTS: Compared to healthy subjects, psoriatics scored lower in
      neuropsychological tests assessing memory and executive functions. CONCLUSIONS:
      Cognitive dysfunction disclosed by neuropsychological assessment of frontal
      functions was evident in patients with psoriasis.

PMID- 28507491
TI  - Association between mean platelet volume and disease severity in patients with
      psoriasis and psoriatic arthritis.
AB  - INTRODUCTION: Mean platelet volume (MPV) is an important marker that shows the
      activation and function of the platelets, which is effective in the inflammatory
      diseases. AIM: To show the relationship between MPV and the development of
      psoriatic arthritis (PA) in patients with psoriasis vulgaris (PV) and the
      correlation between MPV and psoriasis severity score (PASI). MATERIAL AND
      METHODS: Our study included 116 patients with psoriatic arthritis (68 female, 48
      male) and 41 patients in the psoriasis group (19 female, 22 male) and 90 subjects
      in the control group (55 female, 35 male). The demographic data of the patients,
      duration of disease, PASI, the nature of the disease were evaluated
      retrospectively. RESULTS: Mean platelet volume levels of both the PV group (8.79
      +/-0.86 fl) and the PA group (9.18 +/-1.26 fl) were significantly higher compared
      to the control group (8.42 +/-0.74 fl). There was a weak statistically positive
      correlation between the PASI and the MPV according to the correlation analysis (r
      = 0.165; p = 0.046). CONCLUSIONS: Our results show that MPV may be helpful as an
      indicator of the clinical course of PV and PA. In this regard, that study should
      be supported by prospective studies to find strong correlations.

PMID- 28507492
TI  - Long-term treatment of chronic plaque psoriasis with biological drugs can control
      platelet activation: targeting the bridge between inflammation and
      atherothrombosis.
AB  - INTRODUCTION: Platelet activation is elevated in moderate to severe psoriasis,
      and the reduction in platelet activation during short-term treatment has already
      been demonstrated. Soluble P-selectin is a well-established marker of platelet
      activation. AIM: To show whether the long-term treatment of psoriasis with
      biological drugs can reduce elevated platelet activation. MATERIAL AND METHODS:
      An observational study of 27 patients with chronic plaque psoriasis, treated with
      infliximab, adalimumab, etanercept, or ustekinumab for up to 12 months was
      conducted. Psoriasis area and severity index (PASI), serum P-selectin and
      interleukin (IL)-6 were monitored throughout the treatment. RESULTS: There was no
      significant correlation between PASI and platelet activation in our patients.
      After 3 months of treatment, a significant reduction in PASI and IL-6 was found,
      while P-selectin was not significantly reduced. When a cohort of patients who had
      shown elevated P-selectin prior to the treatment was evaluated, a significant
      reduction in P-selectin was observed in all 8 patients following 3 months; a
      reduction that was sustained after 6 and 12 months of therapy. CONCLUSIONS: We
      conclude that PASI is not a good predictor of platelet activity in patients with
      PASI near to 10. Biological drugs reduce platelet activation in patients who have
      increased platelet activation prior to treatment, and this effect is stable
      during chronic therapy.

PMID- 28507493
TI  - Comparison of the incidence of skin cancers in patients on dialysis and after
      kidney transplantation.
AB  - INTRODUCTION: Kidney transplant (KTx) patients on immunosuppressive therapy are
      predisposed to the development of infections and cancers. AIM: To compare the
      incidence and type of malignant skin lesions in kidney transplant patients and
      the dialyzed population based on the initiated dermatologic screening. MATERIAL
      AND METHODS: The study included 598 patients: 486 kidney transplant recipients
      and 112 patients on maintenance dialysis. All the patients underwent
      dermatological examination. Only histologically confirmed cancers were included
      in this study. Age, gender and immunosuppressive therapy administration were also
      considered. Patients were followed up by a dermatologist for a period of 5 years.
      RESULTS: Fifty-eight skin cancers; 39 basal cell carcinomas (BCC), 13 squamous
      cell carcinomas (SCC), 1 Bowen disease, 2 Kaposi sarcoma, 1 malignant melanoma, 1
      Merkel cell carcinoma, and 1 fibrosarcoma protuberans were diagnosed in 30 (6.2%)
      kidney transplant patients, and 8 lesions (7 BCC and 1 SCC) were found in 4
      (3.6%) patients on dialysis. CONCLUSIONS: The initiated dermatologic screening
      program indicates that the risk of skin cancer incidence in post kidney
      transplant patients receiving immunosuppressive therapy was significantly higher
      than in patients on dialysis.

PMID- 28507494
TI  - Sleep patterns of young children with newly diagnosed atopic dermatitis.
AB  - INTRODUCTION: Even though atopic dermatitis (AD) most often begins in the first
      year of life, it is not well known whether sleep disturbances occur following the
      onset of the disease or whether they develop later. AIM: To determine the sleep
      patterns of young children already diagnosed with AD in comparison to a control
      group by using a validated questionnaire, the Brief Infant Sleep Questionnaire
      (BISQ). MATERIAL AND METHODS: Forty-six children with a new diagnosis of AD and
      60 healthy children, aged 3-36 months, participated in the study. Their sleep
      behaviors were assessed using the BISQ along with a structured sociodemographic
      data form. RESULTS: It was found that when compared with healthy children,
      children with AD did not have decreased daily total sleep duration (p = 0.1);
      however, it was found that they woke up more frequently at night (52.2% vs. 40%,
      p = 0.4) and they stayed awake significantly longer than 60 min when they woke up
      (41.3% vs. 11.7%, p < 0.05). In addition, mothers of children with AD reported
      that their children had three times as many sleep problems compared to the
      reports of mothers of healthy children. CONCLUSIONS: The findings of this study
      showed that sleep disturbance was more common in young children with already
      diagnosed AD, and the BISQ provided a practical way to assess the sleep patterns.
      The use of a screening tool to enable early identification and treatment of
      childhood sleep problems among patients with AD should be encouraged.

PMID- 28507495
TI  - The pharmacotherapy preferred by doctors in treatment of patients diagnosed with
      asthma or chronic obstructive pulmonary disease or allergic rhinitis and
      concomitant diseases: an epidemiological analysis.
AB  - INTRODUCTION: The clinical course of asthma and chronic obstructive pulmonary
      disease (COPD) is influenced by the co-occurrence of other chronic diseases and
      their pharmacotherapy. There are no data associated with the doctors'
      pharmacotherapy preferences in treatment of patients with asthma, COPD or
      allergic rhinitis and concomitant diseases. AIM: The assessment of doctors'
      preferences in pharmacotherapy of asthma, COPD or allergic rhinitis in relation
      to concomitant diseases. MATERIAL AND METHODS: General practitioners,
      pulmonologists, allergists, laryngologists and paediatricians (n = 319)
      participated in a questionnaire survey concerning their preferences in
      pharmacotherapy of asthma, COPD and allergic rhinitis in relation to concomitant
      diseases enrolling 11,310 patients with asthma, COPD and allergic rhinitis.
      RESULTS: The concomitant diseases were reported in 58.5% of patients with asthma,
      80.8% of patients with COPD and 46.4% of patients with allergic rhinitis.
      Patients with asthma were most frequently treated with inhaled
      glucocorticosteroids. However, in the subgroups with concomitant diseases, an
      increased usage of inhaled long-acting beta2-mimetics was noted. Regardless of
      comorbidities, patients with COPD were most frequently treated with inhaled long
      acting beta2-mimetics whereas patients with allergic rhinitis - with nasal
      glucocorticosteroids and third-generation antihistamines. CONCLUSIONS: The co
      occurrence of chronic diseases was most frequent among patients diagnosed with
      COPD. The treatment of asthma, COPD and allergic rhinitis is consistent with
      international recommendations and the occurrence of concomitant diseases did not
      significantly influence therapeutic preferences and decisions.

PMID- 28507498
TI  - Pruritus ani and perianal eczema as a manifestation of systemic contact
      dermatitis.

PMID- 28507496
TI  - Safety and efficacy of venom immunotherapy: a real life study.
AB  - INTRODUCTION: Venom immunotherapy (VIT) is recommended as the first-line
      treatment for patients allergic to Hymenoptera venom. AIM: To analyze the safety
      and efficacy of VIT in a real life setting. MATERIAL AND METHODS: One hundred and
      eighty patients undergoing VIT were studied to evaluate the safety, efficacy,
      incidence and nature of symptoms after field stings and adverse reactions to VIT.
      RESULTS: Significantly more patients were allergic to wasp than bee venom (146
      vs. 34, p < 0.0001). Early and late side effects were more common during the
      maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients,
      17.8%), were more frequent in patients allergic to bees, and were not associated
      with angiotensin convertase inhibitors (ACEi) or beta-adrenergic antagonists use.
      Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6
      patients allergic to bees (17.65%). The VIT was efficacious as most patients
      reported no reactions (50%) or reported only mild local reactions (43.75%) to
      field stings. The decrease in sIgE at completion of VIT correlated with the dose
      of vaccine received (r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001)
      and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom
      allergy. CONCLUSIONS: Venom immunotherapy is highly efficacious and safe as most
      of the adverse events during the induction and maintenance phase are mild and
      local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and
      female sex are associated with a higher risk of allergy to Hymenoptera venom.

PMID- 28507497
TI  - Sense of coherence as a protective factor in chronic urticaria.
AB  - INTRODUCTION: Chronic urticaria (CU) seems to be perceived as a
      psychodermatological disorder. Different psychological factors play an important
      role in CU triggering and course. One of them is a sense of coherence (SOC),
      which is believed to be a protective factor against anxiety and depression. AIM:
      To investigate quality of life (QoL) in CU patients and to compare selected
      psychological parameters (anxiety, depression and sense of coherence) between CU
      individuals and the control group. MATERIAL AND METHODS: The study comprised 46
      female patients with chronic urticaria and 33 healthy females as a control group.
      The following methods were employed: Urticaria Activity Score (UAS), Hospital
      Anxiety and Depression Scale (HADS), Sense of Coherence Questionnaire (SOC-29)
      and Dermatology Life Quality Index (DLQI). RESULTS: The CU patients presented a
      significantly higher anxiety level in comparison to the control group (z = 4.488;
      p < 0.001). There were no statistically significant differences regarding
      depression intensity and SOC. In both groups anxiety and depression negatively
      correlated with global SOC and all its components. Disease severity positively
      correlated with QoL (rho = 0.46, p < 0.01) and negatively with global SOC (rho = 
      0.33, p < 0.05). CONCLUSIONS: Bearing in mind higher prevalence of anxiety and
      depressive symptoms in our CU group, it would be useful to perform screening of
      these aspects in all CU patients and subsequently develop respective
      psychological interventions, based on enhancement of personal resources.

PMID- 28507500
TI  - The coexistence of Darier's disease and Hailey-Hailey disease symptoms.

PMID- 28507499
TI  - Linear cutaneous lupus erythematosus/discoid lupus erythematosus in an adult.

PMID- 28507501
TI  - Supermedicus Award for Professor Cezary Kowalewski.

PMID- 28507502
TI  - Node Identification Using Inter-Regional Correlation Analysis for Mapping
      Detailed Connections in Resting State Networks.
AB  - Brain function is often characterized by the connections and interactions between
      highly interconnected brain regions. Pathological disruptions in these networks
      often result in brain dysfunction, which manifests as brain disease. Typical
      analysis investigates disruptions in network connectivity based correlations
      between large brain regions. To obtain a more detailed description of disruptions
      in network connectivity, we propose a new method where functional nodes are
      identified in each region based on their maximum connectivity to another brain
      region in a given network. Since this method provides a unique approach to
      identifying functionally relevant nodes in a given network, we can provide a more
      detailed map of brain connectivity and determine new measures of network
      connectivity. We applied this method to resting state fMRI of Alzheimer's disease
      patients to validate our method and found decreased connectivity within the
      default mode network. In addition, new measure of network connectivity revealed a
      more detailed description of how the network connections deteriorate with disease
      progression. This suggests that analysis using key relative network hub regions
      based on regional correlation can be used to detect detailed changes in resting
      state network connectivity.

PMID- 28507503
TI  - Improving Challenge/Skill Ratio in a Multimodal Interface by Simultaneously
      Adapting Game Difficulty and Haptic Assistance through Psychophysiological and
      Performance Feedback.
AB  - In order to harmonize robotic devices with human beings, the robots should be
      able to perceive important psychosomatic impact triggered by emotional states
      such as frustration or boredom. This paper presents a new type of biocooperative
      control architecture, which acts toward improving the challenge/skill relation
      perceived by the user when interacting with a robotic multimodal interface in a
      cooperative scenario. In the first part of the paper, open-loop experiments
      revealed which physiological signals were optimal for inclusion in the feedback
      loop. These were heart rate, skin conductance level, and skin conductance
      response frequency. In the second part of the paper, the proposed controller,
      consisting of a biocooperative architecture with two degrees of freedom,
      simultaneously modulating game difficulty and haptic assistance through
      performance and psychophysiological feedback, is presented. With this setup, the
      perceived challenge can be modulated by means of the game difficulty and the
      perceived skill by means of the haptic assistance. A new metric (FlowIndex) is
      proposed to numerically quantify and visualize the challenge/skill relation. The
      results are contrasted with comparable previously published work and show that
      the new method afforded a higher FlowIndex (i.e., a superior challenge/skill
      relation) and an improved balance between augmented performance and user
      satisfaction (higher level of valence, i.e., a more enjoyable and satisfactory
      experience).

PMID- 28507504
TI  - Effects of alpha2A Adrenoceptors on Norepinephrine Secretion from the Locus
      Coeruleus during Chronic Stress-Induced Depression.
AB  - Chronic stressors can often lead to the development of psychological disorders,
      such as depression and anxiety. The locus coeruleus (LC) is a stress sensitive
      brain region located in the pons, with noradrenergic neurons that project to the
      hypothalamus, especially the paraventricular nucleus (PVN) of the hypothalamus.
      The purpose of this paper is to better understand how alpha 2A-adrenoceptors
      (alpha2A-ARs) and LC-hypothalamus noradrenergic system participate in the
      pathophysiological mechanism of depression. In vivo norepinephrine (NE) release
      in the PVN triggered by electrical stimulation in the LC was detected with carbon
      fiber electrodes in depression model of rats induced by chronic unpredictable
      mild stress (CUMS). Also, the extracellular level of NE in the PVN was measured
      by microdialysis in vivo without any stimulation in the LC. The alpha 2
      adrenoceptor (alpha2-AR) antagonist yohimbine and alpha2A-ARs antagonist BRL
      44408 maleate were systemically administered to rats to determine the effects of
      alpha2A-ARs on NE release in the PVN. The peak value of elicited NE release
      signals in the PVN induced by electrical stimulation in the LC in the CUMS rats
      were lower than that in the control rats. The extracellular levels of NE in the
      PVN of the CUMS rats were significantly less than that of the control rats.
      Intraperitoneal injection of yohimbine or BRL-44408 maleate significantly
      potentiated NE release in the PVN of the CUMS rats. The CUMS significantly
      increased protein expression levels of alpha2A-AR in the hypothalamus, and BRL
      44408 maleate significantly reversed the increase of alpha2A-AR protein
      expression levels in the CUMS rats. Our results suggest that the CUMS could
      significantly facilitate the effect of alpha2-adrenoceptor-mediated presynaptic
      inhibition and decrease the release of NE in the PVN from LC. Blockade of the
      inhibitory action of excessive alpha2A-adrenergic receptors in the CUMS rats
      could increase the level of NE in the PVN, which is effective in the treatment of
      depressive disorders.

PMID- 28507506
TI  - Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by
      Calmodulin.
AB  - HIGHLIGHTS - Calmodulin-dependent Kv7.2 current density without the need of
      binding calcium.- Kv7.2 current density increase is accompanied with resistance
      to PI(4,5)P2 depletion.- Kv7.3 current density is insensitive to calmodulin
      elevation.- Kv7.3 is more sensitive to PI(4,5)P2 depletion in the presence of
      calmodulin.- Apo-calmodulin influences PI(4,5)P2 dependence in a subunit specific
      manner. The identification and understanding of critical factors regulating M
      current functional density, whose main components are Kv7.2 and Kv7.3 subunits,
      has profound pathophysiological impact given the important role of the M-current
      in neuronal excitability control. We report the increase in current density of
      Kv7.2 channels by calmodulin (CaM) and by a mutant CaM unable to bind Ca2+
      (CaM1234) revealing that this potentiation is calcium independent. Furthermore,
      after co-expressing a CaM binding protein (CaM sponge) to reduce CaM cellular
      availability, Kv7.2 current density was reduced. Current inhibition after
      transient depletion of the essential Kv7 co-factor phosphatidylinositol-4,5
      bisphosphate (PI(4,5)P2) by activating Danio rerio voltage sensitive phosphatase
      (DrVSP) was blunted by co-expressing CaM1234 or the CaM sponge. In addition, CaM
      dependent potentiation was occluded by tonic elevation of PI(4,5)P2 levels by
      PI(4)P5-kinase (PIP5K) expression. In contrast to the effect on homomeric Kv7.2
      channels, CaM1234 failed to potentiate heteromeric Kv7.2/3 or homomeric Kv7.3
      channels. Sensitivity to PI(4,5)P2 depletion of Kv7.2/3 channels was increased
      after expression of CaM1234 or the CaM sponge, while that of homomeric Kv7.3 was
      unaltered. Altogether, the data reveal that apo-CaM influences PI(4,5)P2
      dependence of Kv7.2, Kv7.2/3, and of Kv7.3 channels in a subunit specific manner.

PMID- 28507505
TI  - Protein-Protein Interaction Among the FoxP Family Members and their Regulation of
      Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System.
AB  - The Forkhead transcription factor FOXP2 is implicated in speech perception and
      production. The avian homolog, FoxP2 contributes to song learning and production
      in birds. In human cell lines, transcriptional activity of FOXP2 requires homo
      dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP
      dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2
      and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song
      control region in zebra finches. We now report on dimer- and oligomerization of
      zebra finch FoxPs and how this affects transcription. In cell lines and in the
      brain we identify homo- and hetero-dimers, and an oligomer composed of FoxP1/2/4.
      We further show that FoxP1/2 but not FoxP4 bind to the regulatory region of the
      target gene Contactin-associated protein-like 2 (CNTNAP2). In addition, we
      demonstrate that FoxP1/4 bind to the regulatory region of very low density
      lipoprotein receptor (VLDLR), as has been shown for FoxP2 previously.
      Interestingly, FoxP1/2/4 individually or in combinations regulate the promoters
      for SV40, zebra finch VLDLR and CNTNAP2 differentially. These data exemplify the
      potential for complex transcriptional regulation of FoxP1/2/4, highlighting the
      need for future functional studies dissecting their differential regulation in
      the brain.

PMID- 28507508
TI  - Improving Focal Photostimulation of Cortical Neurons with Pre-derived Wavefront
      Correction.
AB  - Recent progress in neuroscience to image and investigate brain function has been
      made possible by impressive developments in optogenetic and opto-molecular tools.
      Such research requires advances in optical techniques for the delivery of light
      through brain tissue with high spatial resolution. The tissue causes distortions
      to the wavefront of the incoming light which broadens the focus and consequently
      reduces the intensity and degrades the resolution. Such effects are detrimental
      in techniques requiring focal stimulation. Adaptive wavefront correction has been
      demonstrated to compensate for these distortions. However, iterative derivation
      of the corrective wavefront introduces time constraints that limit its
      applicability to probe living cells. Here, we demonstrate that we can pre
      determine and generalize a small set of Zernike modes to correct for aberrations
      of the light propagating through specific brain regions. A priori identification
      of a corrective wavefront is a direct and fast technique that improves the
      quality of the focus without the need for iterative adaptive wavefront
      correction. We verify our technique by measuring the efficiency of two-photon
      photolysis of caged neurotransmitters along the dendrites of a whole-cell patched
      neuron. Our results show that encoding the selected Zernike modes on the
      excitation light can improve light propagation through brain slices of rats as
      observed by the neuron's evoked excitatory post-synaptic potential in response to
      localized focal uncaging at the spines of the neuron's dendrites.

PMID- 28507510
TI  - Enhanced Axonal Extension of Subcortical Projection Neurons Isolated from Murine
      Embryonic Cortex using Neuropilin-1.
AB  - The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)
      derived neurons can survive in the brain and extend axons to the spinal cord. For
      efficient cell integration to the corticospinal tract (CST) after
      transplantation, the induction or selection of cortical motor neurons is
      important. However, precise information about the appropriate cell population
      remains unclear. To address this issue, we isolated cells expressing Neuropilin-1
      (NRP1), a major axon guidance molecule receptor during the early developmental
      stage, from E14.5 mouse embryonic frontal cortex by fluorescence-activated cell
      sorting. Aggregates of NRP1+ cells gradually expressed subcortical projection
      neuron markers, Ctip2 and VGluT1, and axon guidance molecule receptors, Robo1 and
      deleted in colorectal calcinoma (Dcc), in vitro, suggesting that they contained
      early-stage subcortical projection neurons. We transplanted NRP1+ cells into the
      frontal cortex of P2 neonatal mice. Compared with grafts derived from NRP1- or
      unsorted cells, those derived from NRP1+ cells extended a larger number of axons
      to the spinal cord along the CST. Our data suggest that sorting NRP1+ cells from
      the embryonic cerebral cortex enriches subcortical projection neurons to
      reconstruct the CST.

PMID- 28507509
TI  - Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the
      Developing Cerebral Cortex.
AB  - The Elongator complex is required for proper development of the cerebral cortex.
      Interfering with its activity in vivo delays the migration of postmitotic
      projection neurons, at least through a defective alpha-tubulin acetylation.
      However, this complex is already expressed by cortical progenitors where it may
      regulate the early steps of migration by targeting additional proteins. Here we
      report that connexin-43 (Cx43), which is strongly expressed by cortical
      progenitors and whose depletion impairs projection neuron migration, requires
      Elongator expression for its proper acetylation. Indeed, we show that Cx43
      acetylation is reduced in the cortex of Elp3cKO embryos, as well as in a
      neuroblastoma cell line depleted of Elp1 expression, suggesting that Cx43
      acetylation requires Elongator in different cellular contexts. Moreover, we show
      that histones deacetylase 6 (HDAC6) is a deacetylase of Cx43. Finally, we report
      that acetylation of Cx43 regulates its membrane distribution in apical
      progenitors of the cerebral cortex.

PMID- 28507507
TI  - PINK1/Parkin-Dependent Mitochondrial Surveillance: From Pleiotropy to Parkinson's
      Disease.
AB  - Parkinson's disease (PD) is one of the most frequent neurodegenerative disease
      caused by the preferential, progressive degeneration of the dopaminergic (DA)
      neurons of the substantia nigra (SN) pars compacta. PD is characterized by a
      multifaceted pathological process involving protein misfolding, mitochondrial
      dysfunction, neuroinflammation and metabolism deregulation. The molecular
      mechanisms governing the complex interplay between the different facets of this
      process are still unknown. PARK2/Parkin and PARK6/PINK1, two genes responsible
      for familial forms of PD, act as a ubiquitous core signaling pathway, coupling
      mitochondrial stress to mitochondrial surveillance, by regulating mitochondrial
      dynamics, the removal of damaged mitochondrial components by mitochondria-derived
      vesicles, mitophagy, and mitochondrial biogenesis. Over the last decade,
      PINK1/Parkin-dependent mitochondrial quality control emerged as a pleiotropic
      regulatory pathway. Loss of its function impinges on a number of physiological
      processes suspected to contribute to PD pathogenesis. Its role in the regulation
      of innate immunity and inflammatory processes stands out, providing compelling
      support to the contribution of non-cell-autonomous immune mechanisms in PD. In
      this review, we illustrate the central role of this multifunctional pathway at
      the crossroads between mitochondrial stress, neuroinflammation and metabolism. We
      discuss how its dysfunction may contribute to PD pathogenesis and pinpoint major
      unresolved questions in the field.

PMID- 28507511
TI  - Distribution of ELOVL4 in the Developing and Adult Mouse Brain.
AB  - ELOngation of Very Long chain fatty acids (ELOVL)-4 is essential for the
      synthesis of very long chain-fatty acids (fatty acids with chain lengths >= 28
      carbons). The functions of ELOVL4 and its very long-chain fatty acid products are
      poorly understood at present. However, mutations in ELOVL4 cause
      neurodevelopmental or neurodegenerative diseases that vary according to the
      mutation and inheritance pattern. Heterozygous inheritance of different ELOVL4
      mutations causes Stargardt-like Macular Dystrophy or Spinocerebellar Ataxia type
      34. Homozygous inheritance of ELOVL4 mutations causes more severe disease
      characterized by seizures, intellectual disability, ichthyosis, and premature
      death. To better understand ELOVL4 and very long chain fatty acid function in the
      brain, we examined ELOVL4 expression in the mouse brain between embryonic day 18
      and postnatal day 60 by immunolabeling using ELOVL4 and other marker antibodies.
      ELOVL4 was widely expressed in a region- and cell type-specific manner, and was
      restricted to cell bodies, consistent with its known localization to endoplasmic
      reticulum. ELOVL4 labeling was most prominent in gray matter, although labeling
      also was present in some cells located in white matter. ELOVL4 was widely
      expressed in the developing brain by embryonic day 18 and was especially
      pronounced in regions underlying the lateral ventricles and other neurogenic
      regions. The basal ganglia in particular showed intense ELOVL4 labeling at this
      stage. In the postnatal brain, cerebral cortex, hippocampus, cerebellum,
      thalamus, hypothalamus, midbrain, pons, and medulla all showed prominent ELOVL4
      labeling, although ELOVL4 distribution was not uniform across all cells or
      subnuclei within these regions. In contrast, the basal ganglia showed little
      ELOVL4 labeling in the postnatal brain. Double labeling studies showed that
      ELOVL4 was primarily expressed by neurons, although presumptive oligodendrocytes
      located in white matter tracts also showed labeling. Little or no ELOVL4 labeling
      was present in astrocytes or radial glial cells. These findings suggest that
      ELOVL4 and its very long chain fatty acid products are important in many parts of
      the brain and that they are particularly associated with neuronal function.
      Specific roles for ELOVL4 and its products in oligodendrocytes and myelin and in
      cellular proliferation, especially during development, are possible.

PMID- 28507512
TI  - Changes in Dopamine Transmission in the Nucleus Accumbens Shell and Core during
      Ethanol and Sucrose Self-Administration.
AB  - Ethanol, like other substances of abuse, preferentially increases dopamine (DA)
      transmission in the rat nucleus accumbens (NAc) following passive administration.
      It remains unclear, however, whether ethanol also increases NAc DA transmission
      following operant oral self-administration (SA). The NAc is made-up of a ventro
      medial compartment, the shell and a dorso-lateral one, the core, where DA
      transmission responds differentially following exposure to drugs of abuse.
      Previous studies from our laboratory investigated changes in dialysate DA in the
      NAc shell and core of rats responding for sucrose pellets and for drugs of abuse.
      As a follow up to these studies, we recently investigated the changes in NAc
      shell and core DA transmission associated to oral SA of a 10% ethanol solution.
      For the purpose of comparison with literature studies utilizing sucrose + ethanol
      solutions, we also investigated the changes in dialysate DA associated to SA of
      20% sucrose and 10% ethanol + 20% sucrose solutions. Rats were trained to acquire
      oral SA of the solutions under a Fixed Ratio 1 (FR1) schedule of nose-poking.
      After training, rats were monitored by microdialysis on three consecutive days
      under response contingent (active), reward omission (extinction trial) and
      response non-contingent (passive) presentation of ethanol, sucrose or ethanol +
      sucrose solutions. Active and passive ethanol administration produced a similar
      increase in dialysate DA in the two NAc subdivisions, while under extinction
      trial DA increased preferentially in the shell compared to the core. Conversely,
      under sucrose SA and extinction DA increased exclusively in the shell. These
      observations provide unequivocal evidence that oral SA of 10% ethanol increases
      dialysate DA in the NAc, and also suggest that stimuli conditioned to ethanol
      exposure contribute to the increase of dialysate DA observed in the NAc following
      ethanol SA. Comparison between the pattern of DA changes detected in the NAc
      subdivisions under sucrose and ethanol SA likewise suggests that the NAc shell
      and core DA play different roles in sucrose as compared to ethanol reinforcement.

PMID- 28507514
TI  - Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord
      Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized
      Cat.
AB  - In a previous study we developed a Machine Learning procedure for the automatic
      identification and classification of spontaneous cord dorsum potentials (CDPs).
      This study further supported the proposal that in the anesthetized cat, the
      spontaneous CDPs recorded from different lumbar spinal segments are generated by
      a distributed network of dorsal horn neurons with structured (non-random)
      patterns of functional connectivity and that these configurations can be changed
      to other non-random and stable configurations after the noceptive stimulation
      produced by the intradermic injection of capsaicin in the anesthetized cat. Here
      we present a study showing that the sequence of identified forms of the
      spontaneous CDPs follows a Markov chain of at least order one. That is, the
      system has memory in the sense that the spontaneous activation of dorsal horn
      neuronal ensembles producing the CDPs is not independent of the most recent
      activity. We used this markovian property to build a procedure to identify
      portions of signals as belonging to a specific functional state of connectivity
      among the neuronal networks involved in the generation of the CDPs. We have
      tested this procedure during acute nociceptive stimulation produced by the
      intradermic injection of capsaicin in intact as well as spinalized preparations.
      Altogether, our results indicate that CDP sequences cannot be generated by a
      renewal stochastic process. Moreover, it is possible to describe some functional
      features of activity in the cord dorsum by modeling the CDP sequences as
      generated by a Markov order one stochastic process. Finally, these Markov models
      make possible to determine the functional state which produced a CDP sequence.
      The proposed identification procedures appear to be useful for the analysis of
      the sequential behavior of the ongoing CDPs recorded from different spinal
      segments in response to a variety of experimental procedures including the
      changes produced by acute nociceptive stimulation. They are envisaged as a useful
      tool to examine alterations of the patterns of functional connectivity between
      dorsal horn neurons under normal and different pathological conditions, an issue
      of potential clinical concern.

PMID- 28507513
TI  - Appetitive Olfactory Learning and Long-Term Associative Memory in Caenorhabditis
      elegans.
AB  - Because of the relative simplicity of its nervous system, Caenorhabditis elegans
      is a useful model organism to study learning and memory at cellular and molecular
      levels. For appetitive conditioning in C. elegans, food has exclusively been used
      as an unconditioned stimulus (US). It may be difficult to analyze neuronal
      circuits for associative memory since food is a multimodal combination of
      olfactory, gustatory, and mechanical stimuli. Here, we report classical
      appetitive conditioning and associative memory in C. elegans, using 1-nonanol as
      a conditioned stimulus (CS), and potassium chloride (KCl) as a US. Before
      conditioning, C. elegans innately avoided 1-nonanol, an aversive olfactory
      stimulus, and was attracted by KCl, an appetitive gustatory stimulus, on assay
      agar plates. Both massed training without an intertrial interval (ITI) and spaced
      training with a 10-min ITI induced significant levels of memory of association
      regarding the two chemicals. Memory induced by massed training decayed within 6
      h, while that induced by spaced training was retained for more than 6 h. Animals
      treated with inhibitors of transcription or translation formed the memory induced
      by spaced training less efficiently than untreated animals, whereas the memory
      induced by massed training was not significantly affected by such treatments. By
      definition, therefore, memories induced by massed training and spaced training
      are classified as short-term memory (STM) and long-term memory (LTM),
      respectively. When animals conditioned by spaced training were exposed to 1
      nonanol alone, their learning index was lower than that of untreated animals,
      suggesting that extinction learning occurs in C. elegans. In support of these
      results, C. elegans mutants defective in nmr-1, encoding an NMDA receptor
      subunit, formed both STM and LTM less efficiently than wild-type animals, while
      mutations in crh-1, encoding a ubiquitous transcription factor CREB required for
      memory consolidation, affected LTM, but not STM. The paradigm established in the
      present study should allow us to elucidate neuronal circuit plasticity for
      appetitive learning and memory in C. elegans.

PMID- 28507515
TI  - Reusable Client-Side JavaScript Modules for Immersive Web-Based Real-Time
      Collaborative Neuroimage Visualization.
AB  - In this paper we present a web-based software solution to the problem of
      implementing real-time collaborative neuroimage visualization. In both clinical
      and research settings, simple and powerful access to imaging technologies across
      multiple devices is becoming increasingly useful. Prior technical solutions have
      used a server-side rendering and push-to-client model wherein only the server has
      the full image dataset. We propose a rich client solution in which each client
      has all the data and uses the Google Drive Realtime API for state
      synchronization. We have developed a small set of reusable client-side object
      oriented JavaScript modules that make use of the XTK toolkit, a popular open
      source JavaScript library also developed by our team, for the in-browser
      rendering and visualization of brain image volumes. Efficient realtime
      communication among the remote instances is achieved by using just a small JSON
      object, comprising a representation of the XTK image renderers' state, as the
      Google Drive Realtime collaborative data model. The developed open-source
      JavaScript modules have already been instantiated in a web-app called MedView, a
      distributed collaborative neuroimage visualization application that is delivered
      to the users over the web without requiring the installation of any extra
      software or browser plugin. This responsive application allows multiple
      physically distant physicians or researchers to cooperate in real time to reach a
      diagnosis or scientific conclusion. It also serves as a proof of concept for the
      capabilities of the presented technological solution.

PMID- 28507518
TI  - Beneficial Effects of Sulforaphane Treatment in Alzheimer's Disease May Be
      Mediated through Reduced HDAC1/3 and Increased P75NTR Expression.
AB  - Alzheimer's disease is an irreversible, progressive neurodegenerative disorder.
      The accumulation of Abeta in the brain is thought to play a causative role in the
      development of cognitive dysfunction in Alzheimer's disease. The p75 neurotrophin
      receptor is of great importance to protect against the Abeta burden and its
      expression is regulated by histone acetylation. This study investigated whether
      the phytochemical sulforaphane, a pan-histone deacetylase inhibitor, up-regulates
      the p75 neurotrophin receptor expression via affecting histone acetylation in
      protection against Alzheimer's disease. We found that sulforaphane ameliorated
      behavioral cognitive impairments and attenuated brain Abeta burden in Alzheimer's
      disease model mice. Additionally, sulforaphane reduced the expression of histone
      deacetylase1, 2, and 3, up-regulated p75 neurotrophin receptor, and increased
      levels of acetylated histone 3 lysine 9 and acetylated histone 4 lysine 12 in the
      cerebral cortex of Alzheimer's disease model mice as well as in Abeta-exposed SH
      SY5Y cells. Furthermore, silencing of histone deacetylase1 and 3, but not histone
      deacetylase2, gene expression with small interfering RNA caused up-regulation of
      p75 neurotrophin receptor in SH-SY5Y cells. In conclusion, this study
      demonstrates that sulforaphane can ameliorate neurobehavioral deficits and reduce
      the Abeta burden in Alzheimer's disease model mice, and the mechanism underlying
      these effects may be associated with up-regulation of p75 neurotrophin receptor
      mediated, apparently at least in part, via reducing the expression of histone
      deacetylase1 and 3.

PMID- 28507517
TI  - The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase
      Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases.
AB  - Prion diseases are neurodegenerative pathologies characterized by the
      accumulation of a protease-resistant form of the cellular prion protein named
      prion protein scrapie (PrPSc) in the brain. PrPSc accumulation in the endoplasmic
      reticulum (ER) result in a dysregulated calcium (Ca2+) homeostasis and subsequent
      initiation of unfolded protein response (UPR) leading to neuronal dysfunction and
      apoptosis. The molecular mechanisms for the transition between adaptation to ER
      stress and ER stress-induced apoptosis are still unclear. Mitogen-activated
      protein kinases (MAPKs) are serine/threonine protein kinases that rule the
      signaling of many extracellular stimuli from plasma membrane to the nucleus.
      However the identification of numerous points of cross talk between the UPR and
      MAPK signaling pathways may contribute to our understanding of the consequences
      of ER stress in prion diseases. Indeed the MAPK signaling network is known to
      regulate cell cycle progression and cell survival or death responses following a
      variety of stresses including misfolded protein response stress. In this article,
      we review the UPR signaling in prion diseases and discuss the triad of MAPK
      signaling pathways. We also describe the role played by MAPK signaling cascades
      in Alzheimer's (AD) and Parkinson's disease (PD). We will also overview the
      mechanisms of cell death and the role of MAPK signaling in prion disease
      progression and highlight potential avenues for therapeutic intervention.

PMID- 28507519
TI  - Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing
      Link in Endotoxin-Induced Hypotension?
AB  - The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory
      cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a
      putative endothelium-derived relaxing factor, and has been hypothesized to play a
      causative role in the pathophysiology of inflammation-induced hypotension. Here,
      we show that xanthurenic acid (XA), the transamination product of 3
      hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of
      a resistance artery, but fails to relax pre-contracted aortic rings. In the
      mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric
      oxide synthase (NOS), and the relaxing action of XA was abrogated by
      pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor.
      Systemic injection of XA reduced blood pressure in mice, and serum levels of XA
      increased by several fold in response to a pulse with the endotoxin,
      lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre
      treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which
      lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648,
      another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data
      identify XA as a novel vasoactive compound and suggest that formation of XA is a
      key event in the pathophysiology of inflammation-induced hypotension.

PMID- 28507520
TI  - In Vitro and In Silico Antidiabetic and Antimicrobial Evaluation of Constituents
      from Kickxia ramosissima (Nanorrhinum ramosissimum).
AB  - Background and Aims:Kickxia ramosissima (Wall.) Janch (or Nanorrhinum
      ramosissimum (Wall.) Betsche is a well-known medicinal plant in Pakistan that is
      traditionally used in diabetic and inflammatory conditions. Because little
      information is available on its phytochemical composition, a range of
      constituents were isolated and evaluated in vitro in assays related to the
      traditional use. Methods: Dried whole plant material was extracted and
      chromatographically fractionated. Isolated constituents were evaluated in silico
      and in vitro in assays related to the traditional use against diabetes
      (inhibition of alpha-glucosidase activity; inhibition of advanced glycation
      endproducts) and in inflammatory conditions (inhibition of AAPH induced linoleic
      acid peroxidation, inhibition of 15-LOX, antimicrobial activity). Results:
      Phytochemical analysis of the extracts and fractions led to isolation of 7
      compounds, including the iridoids kickxiasine (being a new compound),
      mussaenosidic acid, mussaenoside and linarioside; the flavonoids pectolinarigenin
      and pectolinarin; and 4-hydroxy-benzoic acid methyl ester. The iridoids showed
      weak antiglycation activity. The flavonoids, however, showed interesting results
      as pectolinarigenin was highly active compared to pectolinarin. In the alpha
      glucosidase inhibition assay, only weak activity was observed for the iridoids.
      However, the flavonoid pectolinarigenin showed good activity, followed by
      pectolinarin. In the 15-LOX experiment, moderate inhibition was recorded for most
      compounds, the iridoids mussaenosidic acid and mussaenoside being the most
      active. In the AAPH assay, weak or no inhibition was recorded for all compounds.
      The in silico assays for the alpha-glucosidase and 15-LOX assays confirmed the
      results of respective in vitro assays. Pectolinarigenin showed moderate
      antimicrobial activity against Staphylococcus aureus, Plasmodium falciparum K1,
      and Trypanosoma cruzi, but it was not cytotoxic on a human MRC-5 cell line.
      Conclusion: Our findings may in part contribute to explain the traditional use of
      K. ramosissima.

PMID- 28507516
TI  - Body-Brain Connections: The Effects of Obesity and Behavioral Interventions on
      Neurocognitive Aging.
AB  - Obesity is a growing public health problem in the United States, particularly in
      middle-aged and older adults. Although the key factors leading to a population
      increase in body weight are still under investigation, there is evidence that
      certain behavioral interventions can mitigate the negative cognitive and brain
      ("neurocognitive") health consequences of obesity. The two primary behaviors most
      often targeted for weight loss are caloric intake and physical activity. These
      behaviors might have independent, as well as overlapping/synergistic effects on
      neurocognitive health. To date obesity is often described independently from
      behavioral interventions in regards to neurocognitive outcomes, yet there is
      conceptual and mechanistic overlap between these constructs. This review
      summarizes evidence linking obesity and modifiable behaviors, such as physical
      activity and diet, with brain morphology (e.g., gray and white matter volume and
      integrity), brain function (e.g., functional activation and connectivity), and
      cognitive function across the adult lifespan. In particular, we review evidence
      bearing on the following question: Are associations between obesity and brain
      health in aging adults modifiable by behavioral interventions?

PMID- 28507521
TI  - Prime Time Light Exposures Do Not Seem to Improve Maximal Physical Performance in
      Male Elite Athletes, but Enhance End-Spurt Performance.
AB  - Many sports competitions take place during television prime time, a time of the
      day when many athletes have already exceeded their time of peak performance. We
      assessed the effect of different light exposure modalities on physical
      performance and melatonin levels in athletes during prime time. Seventy-two
      young, male elite athletes with a median (interquartile range) age of 23 (21; 29)
      years and maximum oxygen uptake (VO2max) of 63 (58; 66) ml/kg/min were randomly
      assigned to three different light exposure groups: bright light (BRIGHT), blue
      monochromatic light (BLUE), and control light (CONTROL). Each light exposure
      lasted 60 min and was scheduled to start 17 h after each individual's midpoint of
      sleep (median time: 9:17 pm). Immediately after light exposure, a 12-min time
      trial was performed on a bicycle ergometer. The test supervisor and participants
      were blinded to the light condition each participant was exposed to. The median
      received light intensities and peak wavelengths (photopic lx/nm) measured at eye
      level were 1319/545 in BRIGHT, 203/469 in BLUE, and 115/545 in CONTROL. In a
      multivariate analysis adjusted for individual VO2max, total work performed in 12
      min did not significantly differ between the three groups. The amount of exposure
      to non-image forming light was positively associated with the performance gain
      during the time trial, defined as the ratio of the work performed in the first
      and last minute of the time trial, and with stronger melatonin suppression.
      Specifically, a tenfold increase in the exposure to melanopic light was
      associated with a performance gain of 8.0% (95% confidence interval: 2.6, 13.3; P
      = 0.004) and a melatonin decrease of -0.9 pg/ml (95% confidence interval: -1.5, 
      0.3; P = 0.006). Exposure to bright or blue light did not significantly improve
      maximum cycling performance in a 12-min all-out time trial. However, it is
      noteworthy that the estimated difference of 4.1 kJ between BRIGHT and CONTROL
      might represent an important performance advantage justifying further studies. In
      conclusion, we report novel evidence that evening light exposure, which strongly
      impacts the human circadian timing system, enables elite athletes to better
      maintain performance across a 12-min cycling time trial.

PMID- 28507522
TI  - Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans.
AB  - Preclinical research documents that, aside from the primary and secondary
      reinforcing effects of nicotine intake itself, nicotine also acutely enhances the
      reinforcing efficacy of non-drug reinforcers ("rewards"). Study of these effects
      in humans has largely been overlooked, but very recent findings suggest they may
      have clinical implications for more fully understanding the persistence of
      tobacco dependence. This overview first outlines the topic and notes some recent
      human studies indirectly addressing nicotine effects on related responses (e.g.,
      subjective ratings), explaining why those findings do not directly confirm
      enhancement of behavioral reinforcement per se due to nicotine. Then, the
      methodology used in the subsequently presented studies is described,
      demonstrating how those studies specifically did demonstrate enhancement of
      reinforced responding for non-drug rewards. The main section focuses on the
      limited controlled research to date directly assessing nicotine's acute
      reinforcement-enhancing effects in humans, particularly as it relates to
      reinforced behavioral responding for non-drug rewards in non-human animal models.
      After detailing those few existing human studies, we address potential
      consequences of these effects for dependence and tobacco cessation efforts and
      then suggest directions for future research. This research indicates that
      nicotine per se increases responding in humans that is reinforced by some rewards
      (auditory stimuli via music, visual stimuli via video), but perhaps not by others
      (e.g., money). These reinforcement-enhancing effects in smokers are not due to
      dependence or withdrawal relief and can be restored by a small amount of nicotine
      (similar to a smoking lapse), including from e-cigarettes, a non-tobacco nicotine
      product. Future clinical research should examine factors determining which types
      of rewards are (or are not) enhanced by nicotine, consequences of the loss of
      these nicotine effects after quitting smoking, potential individual differences
      in these effects, and the possibility that nicotine via nicotine replacement
      therapy and non-nicotine quit medications may attenuate loss of these effects
      upon quitting. Further study with humans of nicotine's reinforcement-enhancing
      effects may provide a more complete understanding of smoking persistence and
      added mechanisms of cessation medication efficacy.

PMID- 28507523
TI  - Autism Spectrum Disorders and Schizophrenia Spectrum Disorders:
      Excitation/Inhibition Imbalance and Developmental Trajectories.
AB  - Autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) share
      clinical and genetic components that have long been recognized. The two disorders
      co-occur more frequently than would be predicted by their respective prevalence,
      suggesting that a complex, multifactor association is involved. However, DSM-5
      maintains the distinction between ASD, with core social and communication
      impairments, and SSD, including schizophrenia (SCZ), with hallucinations,
      delusions, and thought disorder as essential features. ASD and SSD have common
      biological underpinnings that may emerge early in development and unfold over
      time. One of the hypotheses supporting the similarities in the social and
      cognitive disturbances of ASD and SSD relates to abnormalities in the ratio of
      excitatory to inhibitory cortical activity (E/I imbalance). E/I imbalance in
      neurodevelopmental disorders could be the consequence of abnormalities in genes
      coding for glutamatergic and GABAergic receptors or synaptic proteins followed by
      system derangements. SSD and ASD have been characterized as polygenic disorders
      in which to the onset and progression of disease is triggered by interactions
      among multiple genes. Mammalian target of rapamycin signaling is under intense
      investigation as a convergent altered pathway in the two spectrum disorders.
      Current understanding of shared and divergent patterns between ASD and SSD from
      molecular to clinical aspects is still incomplete and may be implemented by the
      research domain criteria approach.

PMID- 28507525
TI  - Modernizing Relationship Therapy through Social Thermoregulation Theory:
      Evidence, Hypotheses, and Explorations.
AB  - In the present article the authors propose to modernize relationship therapy by
      integrating novel sensor and actuator technologies that can help optimize
      people's thermoregulation, especially as they pertain to social contexts.
      Specifically, they propose to integrate Social Thermoregulation Theory (IJzerman
      et al., 2015a; IJzerman and Hogerzeil, 2017) into Emotionally Focused Therapy by
      first doing exploratory research during couples' therapy, followed by Randomized
      Clinical Trials (RCTs). The authors thus suggest crafting a Social
      Thermoregulation Therapy (STT) as enhancement to existing relationship therapies.
      The authors outline what is known and not known in terms of social
      thermoregulatory mechanisms, what kind of data collection and analyses are
      necessary to better understand social thermoregulatory mechanisms to craft
      interventions, and stress the need to conduct RCTs prior to implementation. They
      further warn against too hastily applying these theoretical perspectives. The
      article concludes by outlining why STT is the way forward in improving
      relationship functioning.

PMID- 28507524
TI  - Changing What You See by Changing What You Know: The Role of Attention.
AB  - Attending is a cognitive process that incorporates a person's knowledge, goals,
      and expectations. What we perceive when we attend to one thing is different from
      what we perceive when we attend to something else. Yet, it is often argued that
      attentional effects do not count as evidence that perception is influenced by
      cognition. I investigate two arguments often given to justify excluding
      attention. The first is arguing that attention is a post-perceptual process
      reflecting selection between fully constructed perceptual representations. The
      second is arguing that attention as a pre-perceptual process that simply changes
      the input to encapsulated perceptual systems. Both of these arguments are highly
      problematic. Although some attentional effects can indeed be construed as post
      perceptual, others operate by changing perceptual content across the entire
      visual hierarchy. Although there is a natural analogy between spatial attention
      and a change of input, the analogy falls apart when we consider other forms of
      attention. After dispelling these arguments, I make a case for thinking of
      attention not as a confound, but as one of the mechanisms by which cognitive
      states affect perception by going through cases in which the same or similar
      visual inputs are perceived differently depending on the observer's cognitive
      state, and instances where cuing an observer using language affects what one
      sees. Lastly, I provide two compelling counter-examples to the critique that
      although cognitive influences on perception can be demonstrated in the
      laboratory, it is impossible to really experience them for oneself in a
      phenomenologically compelling way. Taken together, the current evidence strongly
      supports the thesis that what we know routinely influences what we see, that the
      same sensory input can be perceived differently depending on the current
      cognitive state of the viewer, and that phenomenologically salient demonstrations
      are possible if certain conditions are met.

PMID- 28507527
TI  - Perceived Insider Status and Feedback Reactions: A Dual Path of Feedback
      Motivation Attribution.
AB  - Many studies have evaluated how the characteristics of feedback receiver,
      feedback deliverer and feedback information influence psychological feedback
      reactions of the feedback receiver while largely neglecting that feedback
      intervention is a kind of social interaction process. To address this issue, this
      study proposes that employees' perceived insider status (PIS), as a kind of
      employee-organization relationship, could also influence employees' reactions to
      supervisory feedback. In particular, this study investigates the influence of PIS
      focusing on affective and cognitive feedback reactions, namely feedback
      satisfaction and feedback utility. Surveys were conducted in a machinery
      manufacturing company in the Guangdong province of China. Samples were collected
      from 192 employees. Data analysis demonstrated that PIS and feedback utility
      possessed a U-shaped relationship, whereas PIS and feedback satisfaction
      exhibited positively linear relationships. The analysis identified two kinds of
      mediating mechanisms related to feedback satisfaction and feedback utility.
      Internal feedback motivation attribution partially mediated the relationship
      between PIS and feedback satisfaction but failed to do the same with respect to
      the relationship between PIS and feedback utility. In contrast, external feedback
      motivation attribution partially mediated the relationship between PIS and
      feedback utility while failing to mediate the relationship between PIS and
      feedback satisfaction. Theoretical contributions and practical implications of
      the findings are discussed at the end of the paper.

PMID- 28507526
TI  - Behavioral and Neural Manifestations of Reward Memory in Carriers of Low
      Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor.
AB  - Dopamine is critically important in the neural manifestation of motivated
      behavior, and alterations in the human dopaminergic system have been implicated
      in the etiology of motivation-related psychiatric disorders, most prominently
      addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor
      (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T
      (rs6277) genetic polymorphisms have previously been linked to individual
      differences in striatal dopamine metabolism and clinical risk for alcohol and
      nicotine dependence. Here, we investigated the hypothesis that the variants of
      these polymorphisms would show increased reward-related memory formation, which
      has previously been shown to jointly engage the mesolimbic dopaminergic system
      and the hippocampus, as a potential intermediate phenotype for addiction memory.
      To this end, we performed functional magnetic resonance imaging (fMRI) in 62
      young, healthy individuals genotyped for DRD2 TaqIA and C957T variants.
      Participants performed an incentive delay task, followed by a recognition memory
      task 24 h later. We observed effects of both genotypes on the overall recognition
      performance with carriers of low-expressing variants, namely TaqIA A1 carriers
      and C957T C homozygotes, showing better performance than the other genotype
      groups. In addition to the better memory performance, C957T C homozygotes also
      exhibited a response bias for cues predicting monetary reward. At the neural
      level, the C957T polymorphism was associated with a genotype-related modulation
      of right hippocampal and striatal fMRI responses predictive of subsequent
      recognition confidence for reward-predicting items. Our results indicate that
      genetic variations associated with DRD2 expression affect explicit memory,
      specifically for rewarded stimuli. We suggest that the relatively better memory
      for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an
      intermediate phenotype of addiction memory.

PMID- 28507528
TI  - Cognitive Impairments in Occupational Burnout - Error Processing and Its Indices
      of Reactive and Proactive Control.
AB  - The presented study refers to cognitive aspects of burnout as the effects of long
      term work-related stress. The purpose of the study was to investigate
      electrophysiological correlates of burnout to explain the mechanisms of the core
      burnout symptoms: exhaustion and depersonalization/cynicism. The analyzed error
      related electrophysiological markers shed light on impaired cognitive mechanisms
      and the specific changes in information-processing in burnout. In the EEG study
      design (N = 80), two components of error-related potential (ERP), error-related
      negativity (ERN), and error positivity (Pe), were analyzed. In the non-clinical
      burnout group (N = 40), a significant increase in ERN amplitude and a decrease in
      Pe amplitude were observed compared to controls (N = 40). Enhanced error
      detection, indexed by increased ERN amplitude, and diminished response
      monitoring, indexed by decreased Pe amplitude, reveal emerging cognitive problems
      in the non-clinical burnout group. Cognitive impairments in burnout subjects
      relate to both reactive and unconscious (ERN) and proactive and conscious (Pe)
      aspects of error processing. The results indicate a stronger 'reactive control
      mode' that can deplete resources for proactive control and the ability to
      actively maintain goals. The analysis refers to error processing and specific
      task demands, thus should not be extended to cognitive processes in general. The
      characteristics of ERP patterns in burnout resemble psychophysiological indexes
      of anxiety (increased ERN) and depressive symptoms (decreased Pe), showing to
      some extent an overlapping effect of burnout and related symptoms and disorders.
      The results support the scarce existing data on the psychobiological nature of
      burnout, while extending and specifying its cognitive characteristics.

PMID- 28507529
TI  - Parkinson Disease: An Evolutionary Perspective.
AB  - There are two central premises to this evolutionary view of Parkinson disease
      (PD). First, PD is a specific human disease. Second, the prevalence of PD has
      increased over the course of human history. Several lines of evidence may explain
      why PD appears to be restricted to the human species. The major manifestations of
      PD are the consequence of degeneration in the dopamine-synthesizing neurons of
      the mesostriatal neuronal pathway. It is of note the enormous expansion of the
      human dopamine mesencephalic neurons onto the striatum compared with other
      mammals. Hence, an evolutionary bottle neck was reached with the expansion of the
      massive nigrostriatal axonal arborization. This peculiar nigral overload may
      partly explain the selective fragility of the human dopaminergic mesencephalic
      neurotransmission and the unique presence of PD in humans. On the other hand,
      several facts may explain the increasing prevalence of PD over the centuries. The
      apparently low prevalence of PD before the twentieth century may be related to
      the shorter life expectancy and survival compared to present times. In addition,
      changes in lifestyle over the course of human history might also account for the
      increasing burden of PD. Our hunter-gatherers ancestors invested large energy
      expenditure on a daily basis, a prototypical physical way of life for which our
      genome remains adapted. Technological advances have led to a dramatic reduction
      of physical exercise. Since the brain release of neurotrophic factors (including
      brain-derived neurotrophic factor) is partially exercise related, the marked
      reduction in exercise may contribute to the increasing prevalence of PD.

PMID- 28507530
TI  - Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism Impacts on Migraine
      Susceptibility: A Meta-analysis of Case-Control Studies.
AB  - Inconclusive results have been reported in studies investigating the association
      between the brain-derived neurotrophic factor (BDNF) rs6265 polymorphism and
      migraine. In the present study, we conducted a systematic review and meta
      analysis on the published data in order to quantitatively estimate the
      relationship between rs6265 and migraine susceptibility. A comprehensive search
      was performed through PubMed, Web of Knowledge, and Cochrane databases up to
      October 2016. The pooled odds ratio (OR) with the corresponding 95% confidence
      interval (CI) was calculated to estimate the strength of the association with
      rs6265 under an additive, dominant, or recessive model of inheritance. A total of
      five studies including 1,442 cases and 1,880 controls were identified for the
      meta-analysis. The pooled data showed an increased risk of migraine for the
      allelic (OR: 1.17, 95% CI: 1.03-1.34, p = 0.014) or the dominant model of rs6265
      (OR: 1.22, 95% CI: 1.05-1.41, p = 0.011). Statistical significance of rs6265 was
      lost when one single study was excluded from the analysis (dominant OR: 1.17, 95%
      CI: 1.00-1.38, p = 0.054; allelic OR: 1.14, 95% CI: 0.99-1.31, p = 0.067),
      suggesting lack of robustness of pooled estimates. When stratified by migraine
      type, a similar trend of association was detected with both MA and MO, but a
      statistically significant association of rs6265 was reached only with the MA
      subtype in the dominant model (OR: 1.22, 95% CI: 1.00-1.47, p = 0.047). The
      present meta-analysis supports that BDNF rs6265 may act as a genetic
      susceptibility factor for migraine. Nevertheless, large-scale studies are
      required to confirm our findings and to assess potential modifiers of the
      relationship between rs6265 and migraine.

PMID- 28507531
TI  - Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation
      of Genioglossus in Chronic Intermittent Hypoxic Rats.
AB  - Neuromuscular compensation of the genioglossus muscle can be induced by chronic
      intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway
      stability. Noradrenergic activation of hypoglossal nucleus plays a critical role
      in the central control of the genioglossus. However, it remains unknown whether
      norepinephrine takes part in the central regulation of the genioglossus during
      CIH. Adult male Wistar rats (n = 32) were studied to explore the influence of
      noradrenergic activation of hypoglossal nucleus on the central control of the
      genioglossus at different stages of CIH. The rats were divided into four groups:
      normal control or normoxic (NO) group, CIH group, CIH + normal saline (NS) group,
      and CIH + prazosin (PZ, alpha1-adrenergic antagonist) group. PZ (0.2 mM, 60 nl)
      and NS (0.9%, 60 nl) were microinjected into the hypoglossal nucleus. The
      responses of the genioglossus corticomotor area to transcranial magnetic
      stimulation (TMS) were recorded on the 1st, 7th, 14th, and 21st day of CIH. The
      CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85
      +/- 0.37 vs. 4.58 +/- 0.42, 3.93 +/- 0.17 vs. 4.49 +/- 0.55, 3.79 +/- 0.38 vs.
      4.39 +/- 0.30 ms, P < 0.05), and higher TMS amplitudes on day 1 (2.74 +/- 0.87
      vs. 1.60 +/- 0.52 mV, P < 0.05) of CIH than the NO group. Compared to the CIH +
      NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and
      lower amplitudes) only on the 14th day of CIH (3.99 +/- 0.28 vs. 4.61 +/- 0.48
      ms, 2.51 +/- 0.67 vs. 1.18 +/- 0.62 mV, P < 0.05). These results indicated that
      noradrenergic activation of the hypoglossal nucleus played a role in the central
      compensation of genioglossus through alpha1-adrenoceptor on the 14th day of CIH.

PMID- 28507532
TI  - Spectral Domain-Optical Coherence Tomography As a New Diagnostic Marker for
      Idiopathic Normal Pressure Hydrocephalus.
AB  - PURPOSE: Characterized by a progressive onset of gait disturbances, dementia, and
      urinary incontinence, idiopathic normal pressure hydrocephalus (iNPH) is
      considered a rare, but under-diagnosed disease. Non-invasive diagnostic markers
      are still insufficient to enable the diagnosis of iNPH with certainty and yet
      early treatment with ventriculoperitoneal (VP) shunting can reverse symptoms and
      stop disease progression. Vascular circulation abnormalities in iNPH may be
      reflected by changes in subfoveal and peripapillary choroidal thickness (PPChT).
      This study uses spectral domain-optical coherence tomography (SD-OCT)-based
      measures of retinal and choroidal thickness to test this hypothesis and to assess
      ophthalmological non-invasive markers for iNPH. METHODS: Twelve patients who
      displayed neurological and neuroradiological characteristics of iNPH were subject
      to a full ophthalmological examination including enhanced depth imaging (EDI) SD
      OCT. Of the 12 included iNPH patients, 6 had undergone VP shunting with
      beneficial outcome. Parameters studied with EDI SD-OCT were macular retinal
      thickness (MT), subfoveal choroidal thickness (SFChT), retinal nerve fiber layer
      thickness (RNFL), and PPChT. Results were compared with 13 healthy, age-matched
      controls. RESULTS: Macular thickness and RNFL and MT values of iNPH patients did
      not reflect atrophy. Non-shunted iNPH patients showed significantly lowered
      median PPChT and SFChT values compared to healthy controls. Shunted iNPH patients
      displayed a significantly higher median PPChT and SFChT compared to non-shunted
      iNPH patients. SFChT and PPChT values in shunted patients were not significantly
      different to values in healthy controls. CONCLUSION: Although limited by small
      sample size, SD-OCT measures in this study reveal significant changes of
      choroidal thickness and support the hypothesis of choroidal susceptibility to
      hemodynamic alterations in iNPH. Non-shunted iNPH patients in this study show
      choroidal thinning in combination with normal RNFL and MT values. In addition to
      neurological and neuroradiological exams, this pattern may aid in the challenging
      diagnosis of iNPH.

PMID- 28507535
TI  - Bioreactor Scalability: Laboratory-Scale Bioreactor Design Influences
      Performance, Ecology, and Community Physiology in Expanded Granular Sludge Bed
      Bioreactors.
AB  - Studies investigating the feasibility of new, or improved, biotechnologies, such
      as wastewater treatment digesters, inevitably start with laboratory-scale trials.
      However, it is rarely determined whether laboratory-scale results reflect full
      scale performance or microbial ecology. The Expanded Granular Sludge Bed (EGSB)
      bioreactor, which is a high-rate anaerobic digester configuration, was used as a
      model to address that knowledge gap in this study. Two laboratory-scale
      idealizations of the EGSB-a one-dimensional and a three- dimensional scale-down
      of a full-scale design-were built and operated in triplicate under near-identical
      conditions to a full-scale EGSB. The laboratory-scale bioreactors were seeded
      using biomass obtained from the full-scale bioreactor, and, spent water from the
      distillation of whisky from maize was applied as substrate at both scales. Over
      70 days, bioreactor performance, microbial ecology, and microbial community
      physiology were monitored at various depths in the sludge-beds using 16S rRNA
      gene sequencing (V4 region), specific methanogenic activity (SMA) assays, and a
      range of physical and chemical monitoring methods. SMA assays indicated dominance
      of the hydrogenotrophic pathway at full-scale whilst a more balanced activity
      profile developed during the laboratory-scale trials. At each scale,
      Methanobacterium was the dominant methanogenic genus present. Bioreactor
      performance overall was better at laboratory-scale than full-scale. We observed
      that bioreactor design at laboratory-scale significantly influenced spatial
      distribution of microbial community physiology and taxonomy in the bioreactor
      sludge-bed, with 1-D bioreactor types promoting stratification of each. In the 1
      D laboratory bioreactors, increased abundance of Firmicutes was associated with
      both granule position in the sludge bed and increased activity against acetate
      and ethanol as substrates. We further observed that stratification in the sludge
      bed in 1-D laboratory-scale bioreactors was associated with increased richness in
      the underlying microbial community at species (OTU) level and improved overall
      performance.

PMID- 28507534
TI  - Stress and Alterations in Bones: An Interdisciplinary Perspective.
AB  - Decades of research have demonstrated that physical stress (PS) stimulates bone
      remodeling and affects bone structure and function through complex
      mechanotransduction mechanisms. Recent research has laid ground to the hypothesis
      that mental stress (MS) also influences bone biology, eventually leading to
      osteoporosis and increased bone fracture risk. These effects are likely exerted
      by modulation of hypothalamic-pituitary-adrenal axis activity, resulting in an
      altered release of growth hormones, glucocorticoids and cytokines, as
      demonstrated in human and animal studies. Furthermore, molecular cross talk
      between mental and PS is thought to exist, with either synergistic or
      preventative effects on bone disease progression depending on the characteristics
      of the applied stressor. This mini review will explain the emerging concept of MS
      as an important player in bone adaptation and its potential cross talk with PS by
      summarizing the current state of knowledge, highlighting newly evolving notions
      (such as intergenerational transmission of stress and its epigenetic
      modifications affecting bone) and proposing new research directions.

PMID- 28507533
TI  - Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent
      Roles of PI3K.
AB  - Type I and II cytokine receptors are cell surface sensors that bind cytokines in
      the extracellular environment and initiate intracellular signaling to control
      processes such as hematopoiesis, immune function, and cellular growth and
      development. One key mechanism that regulates signaling from cytokine receptors
      is through receptor endocytosis. In this mini-review, we describe recent advances
      in endocytic regulations of cytokine receptors, focusing on new paradigms by
      which PI3K controls receptor endocytosis through both kinase activity-dependent
      and -independent mechanisms. These advances underscore the notion that the p85
      regulatory subunit of PI3K has functions beyond regulating PI3K kinase activity,
      and that PI3K plays both positive and negative roles in receptor signaling. On
      the one hand, the PI3K/Akt pathway controls various aspects downstream of
      cytokine receptors. On the other hand, it stimulates receptor endocytosis and
      downregulation, thus contributing to signaling attenuation.

PMID- 28507536
TI  - Temporal Genomic Phylogeny Reconstruction Indicates a Geospatial Transmission
      Path of Salmonella Cerro in the United States and a Clade-Specific Loss of
      Hydrogen Sulfide Production.
AB  - Salmonella Cerro has become one of the most prevalent Salmonella serotypes
      isolated from dairy cattle in several U.S. states, including New York where it
      represented 36% of all Salmonella isolates of bovine origin in 2015. This
      serotype is commonly isolated from dairy cattle with clinical signs of
      salmonellosis, including diarrhea and fever, although it has also been identified
      in herds without evidence of clinical disease or decreased production. To better
      understand the transmission patterns and drivers of its geographic spread, we
      have studied the genomic similarity and microevolution of S. Cerro isolates from
      the northeast U.S. and Texas. Eighty-three out of 86 isolates were confirmed as
      multilocus sequence type 367. We identified core genome SNPs in 57 upstate New
      York (NY), 2 Pennsylvania (PA), and 27 Texas S. Cerro isolates from dairy cattle,
      farm environments, raw milk, and one human clinical case and used them to
      construct a tip-dated phylogeny. S. Cerro isolates clustered in three distinct
      clades, including (i) clade I (n = 3; 2013) comprising isolates from northwest
      Texas (NTX), (ii) clade II (n = 14; 2009-2011, 2014) comprising isolates from NY,
      and (iii) clade III comprising isolates from NY, PA, and central Texas (CTX) in
      subclade IIIa (n = 45; 2008-2014), and only CTX isolates in subclade IIIb (n =
      24; 2013). Temporal phylogenetic analysis estimated the divergence of these three
      clades from the most recent common ancestor in approximately 1980. The CTX clade
      IIIb was estimated to have evolved and diverged from the NY ancestor around 2004.
      Furthermore, gradual temporal loss of genes encoding a D-alanine transporter,
      involved in virulence, was observed. These genes were present in the isolates
      endemic to NTX clade I and were gradually lost in clades II and III. The
      virulence gene orgA, which is part of the Salmonella Pathogenicity Island 1, was
      lost in a subgroup of Texas isolates in clades I and IIIb. All S. Cerro isolates
      had an additional cytosine inserted in a cytosine-rich region of the virulence
      gene sopA, resulting in premature termination of translation likely responsible
      for loss of pathogenic capacity in humans. A group of closely related NY isolates
      was characterized by the loss of hydrogen sulfide production due to the
      truncation or complete loss of phsA. Our data suggest the ability of Salmonella
      to rapidly diverge and adapt to specific niches (e.g., bovine niche), and to
      modify virulence-related characteristics such as the ability to utilize
      tetrathionate as an alternative electron acceptor, which is commonly used to
      detect Salmonella. Overall, our results show that clinical outcome data and
      genetic data for S. Cerro isolates, such as truncations in virulence genes
      leading to novel pheno- and pathotypes, should be correlated to allow for
      accurate risk assessment.

PMID- 28507538
TI  - Candida lipolytica UCP0988 Biosurfactant: Potential as a Bioremediation Agent and
      in Formulating a Commercial Related Product.
AB  - The aim of the present study was to investigate the potential application of the
      biosurfactant from Candida lipolytica grown in low-cost substrates, which has
      previously been produced and characterized under optimized conditions as an
      adjunct material to enhance the remediation processes of hydrophobic pollutants
      and heavy metals generated by the oil industry and propose the formulation of a
      safe and stable remediation agent. In tests carried out with seawater, the crude
      biosurfactant demonstrated 80% oil spreading efficiency. The dispersion rate was
      50% for the biosurfactant at a concentration twice that of the CMC. The
      biosurfactant removed 70% of motor oil from contaminated cotton cloth in
      detergency tests. The crude biosurfactant also removed 30-40% of Cu and Pb from
      standard sand, while the isolated biosurfactant removed ~30% of the heavy metals.
      The conductivity of solutions containing Cd and Pb was sharply reduced after
      biosurfactants' addition. A product was prepared through adding 0.2% potassium
      sorbate as preservative and tested over 120 days. The formulated biosurfactant
      was analyzed for emulsification and surface tension under different pH values,
      temperatures, and salt concentrations and tested for toxicity against the fish
      Poecilia vivipara. The results showed that the formulation had no toxicity and
      did not cause significant changes in the tensoactive capacity of the biomolecule
      while maintaining activity demonstrating suitability for potential future
      commercial product formulation.

PMID- 28507537
TI  - Deep Sea Actinomycetes and Their Secondary Metabolites.
AB  - Deep sea is a unique and extreme environment. It is a hot spot for hunting marine
      actinomycetes resources and secondary metabolites. The novel deep sea
      actinomycete species reported from 2006 to 2016 including 21 species under 13
      genera with the maximum number from Microbacterium, followed by Dermacoccus,
      Streptomyces and Verrucosispora, and one novel species for the other 9 genera.
      Eight genera of actinomycetes were reported to produce secondary metabolites,
      among which Streptomyces is the richest producer. Most of the compounds produced
      by the deep sea actinomycetes presented antimicrobial and anti-cancer cell
      activities. Gene clusters related to biosynthesis of desotamide, heronamide, and
      lobophorin have been identified from the deep sea derived Streptomyces.

PMID- 28507539
TI  - New Insight into Inter-kingdom Communication: Horizontal Transfer of Mobile Small
      RNAs.
AB  - Small RNAs (sRNAs), including small interfering RNAs (siRNAs) and microRNAs
      (miRNAs), are conventionally regarded as critical molecular regulators of various
      intracellular processes. However, recent accumulating evidence indicates that
      sRNAs can be transferred within cells and tissues and even across species. In
      plants, nematodes and microbes, these mobile sRNAs can mediate inter-kingdom
      communication, environmental sensing, gene expression regulation, host-parasite
      defense and many other biological functions. Strikingly, a recent study by our
      group suggested that ingested plant miRNAs are transferred to blood, accumulate
      in tissues and regulate transcripts in consuming animals. While our and other
      independent groups' subsequent studies further explored the emerging field of
      sRNA-mediated crosstalk between species, some groups reported negative results
      and questioned its general applicability. Thus, further studies carefully
      evaluating the horizontal transfer of exogenous sRNAs and its potential
      biological functions are urgently required. Here, we review the current state of
      knowledge in the field of the horizontal transfer of mobile sRNAs, suggest its
      future directions and key points for examination and discuss its potential
      mechanisms and application prospects in nutrition, agriculture and medicine.

PMID- 28507540
TI  - Microbial Population Dynamics and Ecosystem Functions of Anoxic/Aerobic Granular
      Sludge in Sequencing Batch Reactors Operated at Different Organic Loading Rates.
AB  - The granular sludge process is an effective, low-footprint alternative to
      conventional activated sludge wastewater treatment. The architecture of the
      microbial granules allows the co-existence of different functional groups, e.g.,
      nitrifying and denitrifying communities, which permits compact reactor design.
      However, little is known about the factors influencing community assembly in
      granular sludge, such as the effects of reactor operation strategies and influent
      wastewater composition. Here, we analyze the development of the microbiomes in
      parallel laboratory-scale anoxic/aerobic granular sludge reactors operated at low
      (0.9 kg m-3d-1), moderate (1.9 kg m-3d-1) and high (3.7 kg m-3d-1) organic
      loading rates (OLRs) and the same ammonium loading rate (0.2 kg NH4-N m-3d-1) for
      84 days. Complete removal of organic carbon and ammonium was achieved in all
      three reactors after start-up, while the nitrogen removal (denitrification)
      efficiency increased with the OLR: 0% at low, 38% at moderate, and 66% at high
      loading rate. The bacterial communities at different loading rates diverged
      rapidly after start-up and showed less than 50% similarity after 6 days, and
      below 40% similarity after 84 days. The three reactor microbiomes were dominated
      by different genera (mainly Meganema, Thauera, Paracoccus, and Zoogloea), but
      these genera have similar ecosystem functions of EPS production, denitrification
      and polyhydroxyalkanoate (PHA) storage. Many less abundant but persistent taxa
      were also detected within these functional groups. The bacterial communities were
      functionally redundant irrespective of the loading rate applied. At steady-state
      reactor operation, the identity of the core community members was rather stable,
      but their relative abundances changed considerably over time. Furthermore,
      nitrifying bacteria were low in relative abundance and diversity in all reactors,
      despite their large contribution to nitrogen turnover. The results suggest that
      the OLR has considerable impact on the composition of the granular sludge
      communities, but also that the granule communities can be dynamic even at steady
      state reactor operation due to high functional redundancy of several key guilds.
      Knowledge about microbial diversity with specific functional guilds under
      different operating conditions can be important for engineers to predict the
      stability of reactor functions during the start-up and continued reactor
      operation.

PMID- 28507541
TI  - The Importance of Bacterial Culture to Food Microbiology in the Age of Genomics.
AB  - Culture-based and genomics methods provide different insights into the nature and
      behavior of bacteria. Maximizing the usefulness of both approaches requires
      recognizing their limitations and employing them appropriately. Genomic analysis
      excels at identifying bacteria and establishing the relatedness of isolates.
      Culture-based methods remain necessary for detection and enumeration, to
      determine viability, and to validate phenotype predictions made on the bias of
      genomic analysis. The purpose of this short paper is to discuss the application
      of culture-based analysis and genomics to the questions food microbiologists
      routinely need to ask regarding bacteria to ensure the safety of food and its
      economic production and distribution. To address these issues appropriate tools
      are required for the detection and enumeration of specific bacterial populations
      and the characterization of isolates for, identification, phylogenetics, and
      phenotype prediction.

PMID- 28507543
TI  - Long-term Monocyte Dysfunction after Sepsis in Humanized Mice Is Related to
      Persisted Activation of Macrophage-Colony Stimulation Factor (M-CSF) and
      Demethylation of PU.1, and It Can Be Reversed by Blocking M-CSF In Vitro or by
      Transplanting Naive Autologous Stem Cells In Vivo.
AB  - The duration of post-sepsis long-term immune suppression is poorly understood.
      Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term
      regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several
      acute conditions, but it is unclear for how long MO aberrancy post-sepsis can
      persist. Interestingly, the positive feedback loop sustaining secretion of
      macrophage-colony stimulation factor (M-CSF) can persist even after resolution of
      sepsis and significantly alters performance of MO. Here, we investigated the
      activation of M-CSF, and it as critical regulator of PU.1 in mice surviving 28
      days after sepsis. Our primary readout was the ability of MO to differentiate
      into dendritic cells (DCs; MO->iDC) in vitro since this is one of the critical
      processes regulating a successful transition from innate to acquired immunity. We
      utilized a survival modification of the cecal ligation and puncture (CLP) model
      of sepsis in humanized mice. Animals were sacrificed 28 days after CLP
      (tCLP+28d). Untouched (CONTR) or sham-operated (SHAM) animals served as controls.
      Some animals received rescue from stem cells originally used for grafting 2 weeks
      after CLP. We found profound decrease of MO->iDC in the humanized mice 28 days
      after sepsis, demonstrated by depressed expression of CD1a, CD83, and CD209,
      diminished production of IL-12p70, and depressed ability to stimulate T cells in
      mice after CLP as compared to SHAM or CONTR. In vitro defect in MO->iDC was
      accompanied by in vivo decrease of BDCA-3+ endogenous circulating DC.
      Interestingly, post-CLP MO had persistent activation of M-CSF pathway, shown by
      exaggerated secretion of M-CSF, activation of PU.1, and demethylation of SPII.
      Neutralization of the M-CSF in vitro reversed the post-CLP MO->iDC aberration.
      Furthermore, transplantation of naive, autologous stem cell-derived MO restored
      CLP-deteriorated ability of MO to become DC, measured as recovery of CD1a
      expression, enhanced production of IL-12p70, and ability of IL-4 and GM-CSF MO to
      stimulate allogeneic T cells. Our results suggest the role of epigenetic mediated
      M-CSF aberration in mediating post-sepsis immune system recovery.

PMID- 28507542
TI  - Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation
      in Oleaginous Microorganisms: The State of the Art and Future Perspectives.
AB  - Microbial oils, which are mainly extracted from yeasts, molds, and algae, have
      been of considerable interest as food additives and biofuel resources due to
      their high lipid content. While these oleaginous microorganisms generally produce
      only small amounts of lipids under optimal growth conditions, their lipid
      accumulation machinery can be induced by environmental stresses, such as nutrient
      limitation and an inhospitable physical environmental. As common second
      messengers of many stress factors, reactive oxygen species (ROS) may act as a
      regulator of cellular responses to extracellular environmental signaling.
      Furthermore, increasing evidence indicates that ROS may act as a mediator of
      lipid accumulation, which is associated with dramatic changes in the
      transcriptome, proteome, and metabolome. However, the specific mechanisms of ROS
      involvement in the crosstalk between extracellular stress signaling and
      intracellular lipid synthesis require further investigation. Here, we summarize
      current knowledge on stress-induced lipid biosynthesis and the putative role of
      ROS in the control of lipid accumulation in oleaginous microorganisms.
      Understanding such links may provide guidance for the development of stress-based
      strategies to enhance microbial lipid production.

PMID- 28507544
TI  - Within-Epitope Interactions Can Bias CTL Escape Estimation in Early HIV
      Infection.
AB  - As human immunodeficiency virus (HIV) begins to replicate within hosts, immune
      responses are elicited against it. Escape mutations in viral epitopes-immunogenic
      peptide parts presented on the surface of infected cells-allow HIV to partially
      evade these responses, and thus rapidly go to fixation. The faster they go to
      fixation, i.e., the higher their escape rate, the larger the selective pressure
      exerted by the immune system is assumed to be. This relation underpins the
      rationale for using escapes to assess the strength of immune responses. However,
      escape rate estimates are often obtained by employing an aggregation procedure,
      where several mutations that affect the same epitope are aggregated into a
      single, composite epitope mutation. The aggregation procedure thus rests upon the
      assumption that all within-epitope mutations have indistinguishable effects on
      immune recognition. In this study, we investigate how violation of this
      assumption affects escape rate estimates. To this end, we extend a previously
      developed simulation model of HIV that accounts for mutation, selection, and
      recombination to include different distributions of fitness effects (DFEs) and
      inter-mutational genomic distances. We use this discrete time Wright-Fisher based
      model to simulate early within-host evolution of HIV for DFEs and apply standard
      estimation methods to infer the escape rates. We then compare true with estimated
      escape rate values. We also compare escape rate values obtained by applying the
      aggregation procedure with values estimated without use of that procedure. We
      find that across the DFEs analyzed, the aggregation procedure alters the
      detectability of escape mutations: large-effect mutations are overrepresented
      while small-effect mutations are concealed. The effect of the aggregation
      procedure is similar to extracting the largest-effect mutation appearing within
      an epitope. Furthermore, the more pronounced the over-exponential decay of the
      DFEs, the more severely true escape rates are underestimated. We conclude that
      the aggregation procedure has two main consequences. On the one hand, it leads to
      a misrepresentation of the DFE of fixed mutations. On the other hand, it conceals
      within-epitope interactions that may generate irregularities in mutation
      frequency trajectories that are thus left unexplained.

PMID- 28507545
TI  - Clinical and Molecular Heterogeneity of RTEL1 Deficiency.
AB  - Typical features of dyskeratosis congenita (DC) resulting from excessive telomere
      shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or
      liver fibrosis. In more severe cases, immune deficiency and recurring infections
      can add to disease severity. RTEL1 deficiency has recently been described as a
      major genetic etiology, but the molecular basis and clinical consequences of
      RTEL1-associated DC are incompletely characterized. We report our observations in
      a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys,
      p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel
      heterozygous mutation p.Val796AlafsX4. The most unifying features were
      hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition,
      three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered
      from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with
      Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous
      recombination defect was detected in patient-derived fibroblasts but not in
      hematopoietic compartment. Notably, in both cellular compartments, differential
      expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts,
      response to ionizing irradiation and non-homologous end joining were not
      impaired. Telomeric circles did not accumulate in patient-derived primary cells
      and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric
      loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative
      exhaustion, spontaneous apoptosis and senescence. Specifically, CD34+ cells
      failed to expand in vitro, B-cell development was compromised, and T-cells did
      not proliferate in long-term culture. Finally, we report on the natural history
      and outcome of our patients. While two patients died from infections,
      hematopoietic stem cell transplantation (HSCT) resulted in sustained engraftment
      in two patients. Whether chemotherapy negatively impacts on the course and onset
      of other DC-related symptoms remains open at present. Early-onset lung disease
      occurred in one of our patients after HSCT. In conclusion, RTEL deficiency can
      show a heterogeneous clinical picture ranging from mild hypocellular BMF with
      B/NK cell lymphopenia to early-onset, very severe, and rapidly progressing
      cellular deficiency.

PMID- 28507546
TI  - Extracellular Signal-Regulated Kinase Signaling in CD4-Expressing Cells Inhibits
      Osteochondromas.
AB  - Defects in cartilage homeostasis can give rise to various skeletal disorders
      including osteochondromas. Osteochondromas are benign bone tumors caused by
      excess accumulation of chondrocytes, the main cell type of cartilage. The
      extracellular signal-regulated kinase (ERK) pathway is a major signaling node
      that functions within chondrocytes to regulate their growth and differentiation.
      However, it is not known whether the ERK pathway in other cell types regulates
      cartilage homeostasis. We show here that mice with a germline deficiency of Erk1
      and a conditional deletion of Erk2 in cells that express CD4, or expressed CD4 at
      one point in development, unexpectedly developed bone deformities. The bone
      lesions were due to neoplastic outgrowths of chondrocytes and disordered growth
      plates, similar to tumors observed in the human disease, osteochondromatosis.
      Chondrocyte accumulation was not due to deletion of Erk2 in the T cells. Rather,
      CD4cre was expressed in cell types other than T cells, including a small fraction
      of chondrocytes. Surprisingly, the removal of T cells accelerated osteochondroma
      formation and enhanced disease severity. These data show for the first time that
      T cells impact the growth of osteochondromas and describe a novel model to study
      cartilage homeostasis and osteochondroma formation.

PMID- 28507547
TI  - Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency
      upon In Vivo and In Vitro Stimulations.
AB  - We sought to identify genes necessary to induce cytoskeletal change in B cells.
      Using gene expression microarray, we compared B cells stimulated with interleukin
      4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility,
      tight aggregates, and extensive microvilli with B cells stimulated with
      lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes
      with 10-fold or greater expression in anti-CD40 + IL-4 stimulated B cells, one of
      these encoded the guanine nucleotide exchange factor (GEF) dedicator of
      cytokinesis 10 (Dock10). IL-4 selectively induced Dock10 expression in B cells.
      Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10
      was expressed at all stages during B cell development. However, specific deletion
      of Dock10 in B cells was associated with a mild phenotype with normal B cell
      development and normal B cell spreading, polarization, motility, chemotaxis,
      aggregation, and Ig class switching. Dock10-deficient B cells showed lower
      proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG
      response to soluble antigen in vivo was lower when Dock10 was specifically
      deleted in B cells. Together, we found that most B cell responses were intact in
      the absence of Dock10. However, specific deletion of Dock10 in B cells was
      associated with a mild reduction in B cell activation in vitro and in vivo.

PMID- 28507548
TI  - Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in
      Macrophages during Salmonella Infection.
AB  - Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and
      downregulation of the iron exporter ferroportin (FPN) is thought to participate
      in the establishment of anemia of inflammation after infection. However, an
      upregulation of FPN has been proposed to limit macrophages iron access to
      intracellular pathogens. Therefore, we studied the iron homeostasis and in
      particular the regulation of FPN after infection with Salmonella enterica serovar
      Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal
      iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp-/-) levels. The
      presence of iron in AcB61 macrophages due to extravascular hemolysis and strong
      erythrophagocytosis activity favored the proliferation of Salmonella in the
      spleen and liver with a concomitant decrease of FPN protein expression. Despite
      systemic iron overload, no or slight increase in Salmonella burden was observed
      in Hamp-/- mice compared to controls. Importantly, FPN expression at both mRNA
      and protein levels was strongly decreased during Salmonella infection in Hamp-/-
      mice. The repression of Fpn mRNA was also observed in Salmonella-infected
      cultured macrophages. In addition, the downregulation of FPN was associated with
      decreased iron stores in both the liver and spleen in infected mice. Our findings
      show that during Salmonella infection, FPN is repressed through an iron and
      hepcidin-independent mechanism. Such regulation likely provides the cellular iron
      indispensable for the growth of Salmonella inside the macrophages.

PMID- 28507550
TI  - Editorial: Parasites in the Tropic-A New Paradigm Shift.

PMID- 28507551
TI  - Deciphering Genomic Regions for High Grain Iron and Zinc Content Using
      Association Mapping in Pearl Millet.
AB  - Micronutrient malnutrition, especially deficiency of two mineral elements, iron
      [Fe] and zinc [Zn] in the developing world needs urgent attention. Pearl millet
      is one of the best crops with many nutritional properties and is accessible to
      the poor. We report findings of the first attempt to mine favorable alleles for
      grain iron and zinc content through association mapping in pearl millet. An
      association mapping panel of 130 diverse lines was evaluated at Delhi, Jodhpur
      and Dharwad, representing all the three pearl millet growing agro-climatic zones
      of India, during 2014 and 2015. Wide range of variation was observed for grain
      iron (32.3-111.9 ppm) and zinc (26.6-73.7 ppm) content. Genotyping with 114
      representative polymorphic SSRs revealed 0.35 mean gene diversity. STRUCTURE
      analysis revealed presence of three sub-populations which was further supported
      by Neighbor-Joining method of clustering and principal coordinate analysis
      (PCoA). Marker-trait associations (MTAs) were analyzed with 267 markers (250 SSRs
      and 17 genic markers) in both general linear model (GLM) and mixed linear model
      (MLM), however, MTAs resulting from MLM were considered for more robustness of
      the associations. After appropriate Bonferroni correction, Xpsmp 2261 (13.34% R2
      value), Xipes 0180 (R2-value of 11.40%) and Xipes 0096 (R2-value of 11.38%) were
      consistently associated with grain iron and zinc content for all the three
      locations. Favorable alleles and promising lines were identified for across and
      specific environments. PPMI 1102 had highest number (7) of favorable alleles,
      followed by four each for PPMFeZMP 199 and PPMI 708 for across the environment
      performance for both grain Fe and Zn content, while PPMI 1104 had alleles
      specific to Dharwad for grain Fe and Zn content. When compared with the reference
      genome Tift 23D2B1-P1-P5, Xpsmp 2261 amplicon was identified in intergenic region
      on pseudomolecule 5, while the other marker, Xipes 0810 was observed to be
      overlapping with aspartic proteinase (Asp) gene on pseudomolecule 3. Thus, this
      study can help in breeding new lines with enhanced micronutrient content using
      marker-assisted selection (MAS) in pearl millet leading to improved well-being
      especially for women and children.

PMID- 28507552
TI  - Genome-Wide Identification and Expression Analysis of the Biotin Carboxyl Carrier
      Subunits of Heteromeric Acetyl-CoA Carboxylase in Gossypium.
AB  - Acetyl-CoA carboxylase is an important enzyme, which catalyzes acetyl-CoA's
      carboxylation to produce malonyl-CoA and to serve as a committed step for de novo
      fatty acid biosynthesis in plastids. In this study, 24 putative cotton BCCP genes
      were identified based on the lately published genome data in Gossypium. Among
      them, 4, 4, 8, and 8 BCCP homologs were identified in Gossypium raimondii, G.
      arboreum, G. hirsutum, and G. barbadense, respectively. These genes were divided
      into two classes based on a phylogenetic analysis. In each class, these homologs
      were relatively conserved in gene structure and motifs. The chromosomal
      distribution pattern revealed that all the BCCP genes were distributed equally on
      corresponding chromosomes or scaffold in the four cotton species. Segmental
      duplication was a predominant duplication event in both of G. hirsutum and G.
      barbadense. The analysis of the expression profile showed that 8 GhBCCP genes
      expressed in all the tested tissues with changed expression levels, and GhBCCP
      genes belonging to class II were predominantly expressed in developing ovules.
      Meanwhile, the expression analysis for the 16 cotton BCCP genes from G.
      raimondii, G. arboreum and G. hirsutum showed that they were induced or
      suppressed by cold or salt stress, and their expression patterns varied among
      different tissues. These findings will help to determine the functional and
      evolutionary characteristics of the BCCP genes in Gossypium species.

PMID- 28507549
TI  - Human Lung Mononuclear Phagocytes in Health and Disease.
AB  - The lungs are vulnerable to attack by respiratory insults such as toxins,
      allergens, and pathogens, given their continuous exposure to the air we breathe.
      Our immune system has evolved to provide protection against an array of potential
      threats without causing collateral damage to the lung tissue. In order to swiftly
      detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)
      together termed mononuclear phagocytes (MNPs)-line the respiratory tract with the
      key task of surveying the lung microenvironment in order to discriminate between
      harmless and harmful antigens and initiate immune responses when necessary. Each
      cell type excels at specific tasks: monocytes produce large amounts of cytokines,
      macrophages are highly phagocytic, whereas DCs excel at activating naive T cells.
      Extensive studies in murine models have established a division of labor between
      the different populations of MNPs at steady state and during infection or
      inflammation. However, a translation of important findings in mice is only
      beginning to be explored in humans, given the challenge of working with rare
      cells in inaccessible human tissues. Important progress has been made in recent
      years on the phenotype and function of human lung MNPs. In addition to a
      substantial population of alveolar macrophages, three subsets of DCs have been
      identified in the human airways at steady state. More recently, monocyte-derived
      cells have also been described in healthy human lungs. Depending on the source of
      samples, such as lung tissue resections or bronchoalveolar lavage, the specific
      subsets of MNPs recovered may differ. This review provides an update on existing
      studies investigating human respiratory MNP populations during health and
      disease. Often, inflammatory MNPs are found to accumulate in the lungs of
      patients with pulmonary conditions. In respiratory infections or inflammatory
      diseases, this may contribute to disease severity, but in cancer patients this
      may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs
      may be targeted or modulated in order to attain favorable responses that can
      improve preventive or treatment strategies against respiratory infections, lung
      cancer, or lung inflammatory diseases.

PMID- 28507555
TI  - Moderate Drought Stress Affected Root Growth and Grain Yield in Old, Modern and
      Newly Released Cultivars of Winter Wheat.
AB  - To determine root growth and grain yield of winter wheat (Triticum aestivum L)
      under moderate drought stress, a nursery experiment and a field trial were
      conducted with or without water stress using three representative cultivars
      released in different years: CW134 (old landrace), CH58 (modern cultivar) and CH1
      (new release). In the nursery experiment, plants were grown in soil-filled
      rhizoboxes under moderate drought (MD, 55% of field capacity) or well-watered
      (WW, 85% of field capacity) conditions. In the field trial, plots were either
      rainfed (moderate drought stress) or irrigated with 30 mm of water at each of
      stem elongation, booting and anthesis stages (irrigated). Compared to drought
      stress, grain yields increased under sufficient water supply in all cultivars,
      particular the newly released cultivar CH1 with 70% increase in the nursery and
      23% in the field. When well-watered (nursery) or irrigated (field), CH1 had the
      highest grain yields compared to the other two cultivars, but produced similar
      yield to the modern cultivar (CH58) under water-stressed (nursery) or rainfed
      (field) conditions. When exposed to drought stress, CW134 had the highest topsoil
      root dry mass in topsoil but lowest in subsoil among the cultivars at stem
      elongation, anthesis, and maturity, respectively; while CH1 had the lowest
      topsoil and highest subsoil root dry mass at respective sampling times. Topsoil
      root mass and root length density were negatively correlated with grain yield for
      the two water treatments in nursery experiment. When water was limited, subsoil
      root mass was positively correlated with thousand kernel weight (TKW). In the
      field trial, CH1 and CH58 used less water during vegetative growth than CW134,
      but after anthesis stage, CH1 used more water than the other two cultivars,
      especially in the soil profile below 100 cm, which was associated with the
      increased TKW. This study demonstrated that greater root mass and root length
      density in subsoil layers, with enhanced access to subsoil water after anthesis,
      contribute to high grain yield when soil water is scarce.

PMID- 28507553
TI  - Virus-Bacteria Rice Co-Infection in Africa: Field Estimation, Reciprocal Effects,
      Molecular Mechanisms, and Evolutionary Implications.
AB  - Simultaneous infection of a single plant by various pathogen species is
      increasingly recognized as an important modulator of host resistance and a driver
      of pathogen evolution. Because plants in agro-ecosystems are the target of a
      multitude of pathogenic microbes, co-infection could be frequent, and
      consequently important to consider. This is particularly true for rapidly
      intensifying crops, such as rice in Africa. This study investigated potential
      interactions between pathogens causing two of the major rice diseases in Africa:
      the Rice yellow mottle virus (RYMV) and the bacterium Xanthomonas oryzae pathovar
      oryzicola (Xoc) in order to: 1/ document virus-bacteria co-infection in rice in
      the field, 2/ explore experimentally their consequences in terms of symptom
      development and pathogen multiplication, 3/ test the hypothesis of underlying
      molecular mechanisms of interactions and 4/ explore potential evolutionary
      consequences. Field surveys in Burkina Faso revealed that a significant
      proportion of rice fields were simultaneously affected by the two diseases. Co
      infection leads to an increase in bacterial specific symptoms, while a decrease
      in viral load is observed compared to the mono-infected mock. The lack of effect
      found when using a bacterial mutant for an effector specifically inducing
      expression of a small RNA regulatory protein, HEN1, as well as a viral genotype
      specific effect, both suggest a role for gene silencing mechanisms mediating the
      within-plant interaction between RYMV and Xoc. Potential implications for
      pathogen evolution could not be inferred because genotype-specific effects were
      found only for pathogens originating from different countries, and consequently
      not meeting in the agrosystem. We argue that pathogen-pathogen-host interactions
      certainly deserve more attention, both from a theoretical and applied point of
      view.

PMID- 28507556
TI  - Differential Effects of Phosphatidylinositol 4-Kinase (PI4K) and 3-Kinase (PI3K)
      Inhibitors on Stomatal Responses to Environmental Signals.
AB  - Specific cellular components including products of phosphatidylinositol (PI)
      metabolism play an important role as signaling molecules in stomatal responses to
      environmental signals. In this study, pharmacological inhibitors of a set of
      cellular components, including PI4-kinase (PI4K) and PI3K, were used to
      investigate stomatal closure in response to CO2, darkness, and abscisic acid
      (ABA). Treatment with PAO, a specific inhibitor of PI4K, specifically inhibited
      the stomatal response to CO2 compared with that to darkness and ABA. In contrast,
      treatment with LY294002, a PI3K-specific inhibitor, specifically inhibited the
      stomatal response to darkness compared with that to CO2 and ABA. The specific
      inhibitory effects of PAO and LY294002 were also observed as changes in the
      spatial density of dot-like structures labeled by green fluorescent protein
      tagged PATROL1, a protein that controls stomatal aperture possibly via regulation
      of H+-ATPase amount in guard cell plasma membranes. Our results suggest an
      important role for PI4K and PI3K in the CO2 and darkness signal transduction
      pathways, respectively, that mediate PATROL1 dynamics.

PMID- 28507554
TI  - Large Differences in Gene Expression Responses to Drought and Heat Stress between
      Elite Barley Cultivar Scarlett and a Spanish Landrace.
AB  - Drought causes important losses in crop production every season. Improvement for
      drought tolerance could take advantage of the diversity held in germplasm
      collections, much of which has not been incorporated yet into modern breeding.
      Spanish landraces constitute a promising resource for barley breeding, as they
      were widely grown until last century and still show good yielding ability under
      stress. Here, we study the transcriptome expression landscape in two genotypes,
      an outstanding Spanish landrace-derived inbred line (SBCC073) and a modern
      cultivar (Scarlett). Gene expression of adult plants after prolonged stresses,
      either drought or drought combined with heat, was monitored. Transcriptome of
      mature leaves presented little changes under severe drought, whereas abundant
      gene expression changes were observed under combined mild drought and heat.
      Developing inflorescences of SBCC073 exhibited mostly unaltered gene expression,
      whereas numerous changes were found in the same tissues for Scarlett. Genotypic
      differences in physiological traits and gene expression patterns confirmed the
      different behavior of landrace SBCC073 and cultivar Scarlett under abiotic
      stress, suggesting that they responded to stress following different strategies.
      A comparison with related studies in barley, addressing gene expression responses
      to drought, revealed common biological processes, but moderate agreement
      regarding individual differentially expressed transcripts. Special emphasis was
      put in the search of co-expressed genes and underlying common regulatory motifs.
      Overall, 11 transcription factors were identified, and one of them matched cis
      regulatory motifs discovered upstream of co-expressed genes involved in those
      responses.

PMID- 28507557
TI  - Exogenous Glutathione Enhances Mercury Tolerance by Inhibiting Mercury Entry into
      Plant Cells.
AB  - Despite the increasing understanding of the crucial roles of glutathione (GSH) in
      cellular defense against heavy metal stress as well as oxidative stress, little
      is known about the functional role of exogenous GSH in mercury (Hg) tolerance in
      plants. Here, we provide compelling evidence that GSH contributes to Hg tolerance
      in diverse plants. Exogenous GSH did not mitigate the toxicity of cadmium (Cd),
      copper (Cu), or zinc (Zn), whereas application of exogenous GSH significantly
      promoted Hg tolerance during seed germination and seedling growth of Arabidopsis
      thaliana, tobacco, and pepper. By contrast, addition of buthionine sulfoximine,
      an inhibitor of GSH biosynthesis, severely retarded seed germination and seedling
      growth of the plants in the presence of Hg. The effect of exogenous GSH on Hg
      specific tolerance was also evident in the presence of other heavy metals, such
      as Cd, Cu, and Zn, together with Hg. GSH treatment significantly decreased H2O2
      and O2- levels and lipid peroxidation, but increased chlorophyll content in the
      presence of Hg. Importantly, GSH treatment resulted in significantly less
      accumulation of Hg in Arabidopsis plants, and thin layer chromatography and
      nuclear magnetic resonance analysis revealed that GSH had much stronger binding
      affinity to Hg than to Cd, Cu, or Zn, suggesting that tight binding of GSH to Hg
      impedes Hg uptake, leading to low Hg accumulation in plant cells. Collectively,
      the present findings reveal that GSH is a potent molecule capable of conferring
      Hg tolerance by inhibiting Hg accumulation in plants.

PMID- 28507558
TI  - ZmDof30 Negatively Regulates the Promoter Activity of the Pollen-Specific Gene
      Zm908.
AB  - The maize (Zea mays) pollen-predominant gene Zm908, a novel small-peptide gene,
      was reported to play critical roles in pollen germination and pollen tube growth
      in our previous work. In this study, we aimed to explore the regulatory mechanism
      of Zm908. The putative promoter of Zm908 was cloned and analyzed. The activity
      analysis of a series of promoter truncations in different tissues of transgenic
      tobacco plants indicated that the Zm908 promoter is pollen-specific and that the 
      126 to -68 region is crucial for pollen expression. The 5' deletion analysis of
      the -126 to -68 region revealed that the -126 to -102 region functions as a
      transcriptional suppression element. ZmDof30, which is predominantly expressed in
      pollen and whole anthers, was cloned and characterized. ZmDof30-GFP localized to
      the nuclei of maize protoplasts and possessed no transcriptional activation
      activity in a yeast system. ZmDof30 could bind to the AAAG elements in p184
      sequence containing the -126 to +58 region of the Zm908 promoter in vitro and in
      vivo, and negatively regulated p184 activity in tobacco leaves. Collectively,
      ZmDof30 may function as a Zm908 transcriptional repressor in pollen, and these
      results may provide a better understanding of the regulation of the Zm908 gene.
      Additionally, the pollen-specific Zm908 promoter may be valuable for genetically
      engineering male sterility.

PMID- 28507559
TI  - The DnaJ Gene Family in Pepper (Capsicum annuum L.): Comprehensive
      Identification, Characterization and Expression Profiles.
AB  - The DnaJ proteins which function as molecular chaperone played critical roles in
      plant growth and development and response to heat stress (HS) and also called
      heat shock protein 40 based on molecular weight. However, little was reported on
      this gene family in pepper. Recently, the release of the whole pepper genome
      provided an opportunity for identifying putative DnaJ homologous. In this study,
      a total of 76 putative pepper DnaJ genes (CaDnaJ01 to CaDnaJ76) were identified
      using bioinformatics methods and classified into five groups by the presence of
      the complete three domains (J-domain, zinc finger domain, and C-terminal domain).
      Chromosome mapping suggested that segmental duplication and tandem duplication
      were occurred in evolution. The multiple stress-related cis-elements were found
      in the promoter region of these CaDnaJ genes, which indicated that the CaDnaJs
      might be involved in the process of responding to complex stress conditions. In
      addition, expression profiles based on RNA-seq showed that the 47 CaDnaJs were
      expressed in at least one tissue tested. The result implied that they could be
      involved in the process of pepper growth and development. qRT-PCR analysis found
      that 80.60% (54/67) CaDnaJs were induced by HS, indicated that they could
      participated in pepper response to high temperature treatments. In conclusion,
      all these results would provide a comprehensive basis for further analyzing the
      function of CaDnaJ members and be also significant for elucidating the
      evolutionary relationship in pepper.

PMID- 28507560
TI  - Corrigendum: Co-expression with the Type 3 Secretion Chaperone CesT from
      Enterohemorrhagic E. coli Increases Accumulation of Recombinant Tir in Plant
      Chloroplasts.
AB  - [This corrects the article on p. 283 in vol. 8, PMID: 28321227.].

PMID- 28507562
TI  - Antivenomics as a tool to improve the neutralizing capacity of the crotalic
      antivenom: a study with crotamine.
AB  - BACKGROUND: Snakebite treatment requires administration of an appropriate
      antivenom that should contain antibodies capable of neutralizing the venom. To
      achieve this goal, antivenom production must start from a suitable immunization
      protocol and proper venom mixtures. In Brazil, antivenom against South American
      rattlesnake (Crotalus durissus terrificus) bites is produced by public
      institutions based on the guidelines defined by the regulatory agency of the
      Brazilian Ministry of Health, ANVISA. However, each institution uses its own
      mixture of rattlesnake venom antigens. Previous works have shown that crotamine,
      a toxin found in Crolatus durissus venom, shows marked individual and
      populational variation. In addition, serum produced from crotamine-negative
      venoms fails to recognize this molecule. METHODS: In this work, we used an
      antivenomics approach to assess the cross-reactivity of crotalic antivenom
      manufactured by IVB towards crotamine-negative venom and a mixture of crotamine
      negative/crotamine-positive venoms. RESULTS: We show that the venom mixture
      containing 20% crotamine and 57% crotoxin produced a strong immunogenic response
      in horses. Antivenom raised against this venom mixture reacted with most venom
      components including crotamine and crotoxin, in contrast to the antivenom raised
      against crotamine-negative venom. CONCLUSIONS: These results indicate that
      venomic databases and antivenomics analysis provide a useful approach for
      choosing the better venom mixture for antibody production and for the subsequent
      screening of antivenom cross-reactivity with relevant snake venom components.

PMID- 28507561
TI  - Deletion Extents Are Not the Cause of Clinical Variability in 22q11.2 Deletion
      Syndrome: Does the Interaction between DGCR8 and miRNA-CNVs Play a Major Role?
AB  - In humans, the most common genomic disorder is the hemizygous deletion of the
      chromosome 22q11.2 region, that results in the "22q11.2 deletion syndrome"
      (22q11.2DS). A peculiarity of 22q11.2DS is its great phenotypic variability that
      makes this pathology a classic example of a syndrome with variable expressivity
      and incomplete penetrance. The reasons for this variability have not been
      elucidated yet, and the molecular substrates underlying the different clinical
      features of 22q11.2DS are still debated. A cohort of 21 patients has been
      analyzed by array CGH in order to detect some of the genetic differences that may
      influence this variability. Two aspects have been investigated: (1) the precise
      localization of the deletion breakpoints within the low copy repeats (LCRs), (2)
      the additional Copy Number Variations (CNVs) elsewhere in the genome, by
      analyzing their gene content. Both protein-coding genes and miRNAs were
      considered, in order to discover possible epistatic interactions between genes of
      the 22q11.2 region and the rest of the genome. Eighteen out of twenty-one
      patients had a deletion of ~3 Mb mediated by LCR22-A and D, whereas 3/21 had a
      smaller deletion. The breakpoints within the LCR22-A and D do not have a major
      role in the phenotypic variability since they are rather clustered and the small
      differences concern genes that are not directly related to clinical signs of
      22q11.2DS. A detailed analysis of the gene content of 22q11.2 deleted region
      indicates that this syndrome could be a bioenergetic disorder or consequence of
      an altered post-transcriptional gene regulation, due to the presence of DGCR8, a
      major player of the microRNA (miRNA) biogenesis. Only four genes with
      mitochondrial function are harbored in the additional CNVs, whereas 11 miRNA, all
      related to biological pathways present in the 22q11.2DS, have been detected in
      19/21 patients. CNVs and miRNAs are new entities that have changed the order of
      complexity at the level of gene expression and regulation, thus CNV-miRNAs (miRNA
      harbored in the CNVs) are potential functional variants that should be considered
      high priority candidate variants in genotype-phenotype association studies.
      Deletion of DGCR8, the main actor in miRNA biogenesis, amplifies this
      variability. To our knowledge, this is the first report that focus on the miRNA
      CNVs in 22q11.2DS, with the aim of trying to better understand their role in the
      variable expressivity and incomplete penetrance.

PMID- 28507563
TI  - Can coffee consumption lower the risk of Alzheimer's disease and Parkinson's
      disease? A literature review.
AB  - In light of the fact that the number of elderly citizens in society is steadily
      increasing, the search for dietary factors which might prolong mental agility is
      growing in significance. Coffee, together with its main ingredient, caffeine, has
      been the focus of much attention from various researchers, as data on its
      beneficial effects on human health continue to accumulate. Most reports indicate
      that moderate coffee consumption may in fact lower the risk for common
      neurodegenerative conditions, i.e. Alzheimer's and Parkinson's diseases.
      Regardless, due to their complex pathogenesis as well as methodology of
      scientific research, the exact impact of coffee consumption remains to be fully
      elucidated. At present, it seems safe to inform the general public that coffee
      drinkers need not fear for their health. Possibly, in the future experts will
      recommend drinking coffee not only to satisfy individual taste preferences but
      also to decrease age-related mental deterioration.

PMID- 28507565
TI  - Laparoscopic and open liver resection - a literature review with meta-analysis.
AB  - INTRODUCTION: In recent years laparoscopic approach to liver resections has
      gained important attention from surgeons worldwide. The aim of this review was to
      compare the results of laparoscopic and open liver resections. MATERIAL AND
      METHODS: We have performed a search in Medline, Embase and the Cochrane Library
      databases. Studies comparing laparoscopic and open liver resections were
      included. RESULTS: No randomized clinical trial were identified. In the 16
      observational studies included in the analysis there were 927 laparoscopic and
      1049 open liver resections. The laparoscopy group had lower blood loss (MD =
      244.93 ml, p < 0.00001), lower odds of transfusion (OR = 0.35, p = 0.0002), lower
      odds of positive margins on pathology report (OR = 0.22, p < 0.00001), lower odds
      of readmission (OR = 0.36, p = 0.04), lower odds of pulmonary (OR = 0.38, p =
      0.003) and cardiac complications (OR = 0.30, p = 0.02) and lower odds of
      postoperative liver failure (OR = 0.24, p = 0.001), but in many cases the results
      were based on a low number of events reported in included studies. CONCLUSIONS:
      Laparoscopic resection of liver yields complications rates comparable to open
      resection, but the results are based on low quality evidence from nonrandomised
      studies.

PMID- 28507566
TI  - Comparison of intra-articular versus intravenous application of tranexamic acid
      in total knee arthroplasty: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: There is much controversy about the optimal application of
      tranexamic acid (TXA) in total knee arthroplasty (TKA). The purpose of this meta
      analysis was to compare the efficacy of the intra-articular and intravenous
      regimens of TXA in TKA. MATERIAL AND METHODS: A literature search of the PubMed,
      Embase and Cochrane Library databases was performed. Randomized controlled trials
      comparing the result of intra-articular and intravenous application of TXA during
      TKA were included. The focus was on the outcomes of blood loss, transfusion
      requirement and thromboembolic complications. RESULTS: Six studies were eligible
      for data extraction and meta-analysis. We found no statistically significant
      difference between intra-articular and intravenous administration of tranexamic
      acid in terms of total blood loss (WMD, 6.01; 95% CI: -96.78 to 108.79; p =
      0.91), drain output (WMD = -20.26; 95% CI: -51.34 to 10.82; p = 0.20), hemoglobin
      drop (WMD = 0.33; 95% CI: -0.31 to 0.98; p = 0.31), or the incidences of
      transfusion (RR = 0.98; 95% CI: 0.56-1.70; p = 0.93) as well as deep vein
      thrombosis (RR = 0.49; 95% CI: 0.09-2.73; p = 0.42). CONCLUSIONS: In comparison
      with intravenous application of TXA, intra-articular application had a comparable
      effect on reducing blood loss and the transfusion rate without increasing the
      complication rate.

PMID- 28507564
TI  - Management of the hormonal syndrome of neuroendocrine tumors.
AB  - Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare
      neoplasms that present many clinical challenges. They characteristically
      synthesize store and secrete a variety of peptides and neuroamines which can lead
      to the development of distinct clinical syndrome, however many are clinically
      silent until late presentation with mass effects. Management strategies include
      surgery cure and cytoreduction with the use of somatostatin analogues.
      Somatostatin have a broad range of biological actions that include inhibition of
      exocrine and endocrine secretions, gut motility, cell proliferation, cell
      survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been
      cloned and characterized. Somatostatin analogues include octreotide and
      lanreotide are effective medical tools in the treatment and present selectivity
      for SSTR2 and SSTR5. During treatment is seen disapperance of flushing,
      normalization of bowel movements and reduction of serotonin and 5-hydroxyindole
      acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by
      specifically inhibiting serotonin synthesis and as such, is a promising potential
      new treatment for patients with carcinoid syndrome. To pancreatic functionig
      neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma.
      Medical management in patients with insulinoma include diazoxide which suppresses
      insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of
      gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 - receptor
      antagonists. In patients with glucagonomas hyperglycaemia can be controlled using
      insulin and oral blood glucose lowering drugs. In malignant glucagonomas
      smatostatin analogues are effective in controlling necrolytic migratory
      erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid
      losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea.

PMID- 28507567
TI  - Performance of pfHRP2 versus pLDH antigen rapid diagnostic tests for the
      detection of Plasmodium falciparum: a systematic review and meta-analysis.
AB  - INTRODUCTION: There have been many inconsistent reports about the performance of
      histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens as rapid
      diagnostic tests (RDTs) for the diagnosis of past Plasmodium falciparum
      infections. This meta-analysis was performed to determine the performance of
      pfHRP2 versus pLDH antigen RDTs in the detection of P. falciparum. MATERIAL AND
      METHODS: After a systematic review of related studies, Meta-DiSc 1.4 software was
      used to calculate the pooled sensitivity, specificity, positive likelihood ratio
      (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Forest
      plots and summary receiver operating characteristic curve (SROC) analysis were
      used to summarize the overall test performance. RESULTS: Fourteen studies which
      met the inclusion criteria were included in the meta-analysis. The summary
      performances for pfHRP2- and pLDH-based tests in the diagnosis of P. falciparum
      infections were as follows: pooled sensitivity, 96.3% (95.8-96.7%) vs. 82.6%
      (81.7-83.5%); specificity, 86.1% (85.3-86.8%) vs. 95.9% (95.4-96.3%); diagnostic
      odds ratio (DOR), 243.31 (97.679-606.08) vs. 230.59 (114.98-462.42); and area
      under ROCs, 0.9822 versus 0.9849 (all p < 0.001). CONCLUSIONS: The two RDTs
      performed satisfactorily for the diagnosis of P. falciparum, but the pLDH tests
      had higher specificity, whereas the pfHRP2 tests had better sensitivity. The
      pfHRP2 tests had slightly greater accuracy compared to the pLDH tests. A
      combination of both antigens might be a more reliable approach for the diagnosis
      of malaria.

PMID- 28507568
TI  - Effect of ramipril/hydrochlorothiazide and ramipril/canrenone combination on
      atrial fibrillation recurrence in hypertensive type 2 diabetic patients with and
      without cardiac autonomic neuropathy.
AB  - INTRODUCTION: The aim of this study was to compare the effect of
      ramipril/canrenone versus ramipril/hydrochlorothiazide (HCTZ) combination on
      atrial fibrillation (AF) recurrence in type 2 diabetic hypertensives with and
      without cardiac autonomic neuropathy (CAN). MATERIAL AND METHODS: A total of 289
      hypertensive type 2 diabetic patients, 95 with CAN, in sinus rhythm but with at
      least two episodes of AF in the previous 6 months were randomized to ramipril 5
      mg plus canrenone 50 mg (titrated to 10/100 mg) or to ramipril 5 mg plus HCTZ
      12.5 mg (titrated to 10/25 mg) or to amlodipine 5 mg (titrated to 10 mg) for 1
      year. Clinic blood pressure (BP) and a 24-h ECG were evaluated monthly. Patients
      were asked to report any episode of symptomatic AF and to perform an ECG as early
      as possible. Serum procollagen type I carboxy-terminal peptide (PIP) and carboxy
      terminal telopeptide of collagen type I (CITP) were evaluated before and after
      each treatment period. RESULTS: Blood pressure was similarly and significantly
      reduced by all treatments. A total of 51% of patients with amlodipine had a
      recurrence of AF, as did 31% of patients with ramipril/HCTZ (p < 0.05 vs.
      amlodipine) and 13% of patients with ramipril/canrenone (p < 0.01 vs. amlodipine
      and p < 0.05 vs. ramipril/HCTZ). A similar trend was found in diabetic patients
      with CAN. Both combinations reduced PIP and increased CITP, but the effects of
      ramipril/canrenone were significantly more marked. CONCLUSIONS: These findings
      suggest that in type 2 diabetic hypertensives, ramipril/canrenone treatment was
      more effective than ramipril/HCTZ in reducing AF recurrence. This could be
      related to the greater improvement in cardiac fibrosis.

PMID- 28507569
TI  - Effects of a novel ascorbate-based protocol on infarct size and ventricle
      function in acute myocardial infarction patients undergoing percutaneous coronary
      angioplasty.
AB  - INTRODUCTION: This study was designed to test the hypothesis that high-dose
      ascorbate prior to reperfusion followed by low chronic oral doses ameliorate
      myocardial reperfusion injury (MRI) in acute myocardial infarction patients
      subjected to primary percutaneous coronary angioplasty (PCA). MATERIAL AND
      METHODS: A randomized double-blind placebo-controlled and multicenter clinical
      trial was performed on acute myocardial infarction (AMI) patients who underwent
      PCA. Sodium ascorbate (320 mmol/l, n = 53) or placebo (n = 46) was infused 30 min
      prior to PCA. Blood samples were drawn at enrolment (M1), after balloon deflation
      (M2), 6-8 h after M2 (M3) and at discharge (M4). Total antioxidant capacity of
      plasma (ferric reducing ability of plasma - FRAP), erythrocyte reduced
      glutathione (GSH) and plasma ascorbate levels were determined in blood samples.
      Cardiac magnetic resonance (CMR) was performed at 7-15 days and 2-3 months
      following PCA. Ninety-nine patients were enrolled. In 67 patients, the first CMR
      was performed, and 40 patients completed follow-up. RESULTS: The ascorbate group
      showed significantly higher ascorbate and FRAP levels and a decrease in the GSH
      levels at M2 and M3 (p < 0.05). There were no significant differences in the
      infarct size, indexed end-systolic volume and ejection fraction at both CMRs.
      There was a significant amelioration in the decreased ejection fraction between
      the first and second CMR in the ascorbate group (p < 0.05). CONCLUSIONS:
      Ascorbate given prior to reperfusion did not show a significant difference in
      infarct size or ejection fraction. However, it improved the change in ejection
      fraction determined between 7-15 days and 2-3 months. This result hints at a
      possible functional effect of ascorbate to ameliorate MRI.

PMID- 28507570
TI  - ScaI atrial natriuretic peptide gene polymorphisms and their possible association
      with postoperative atrial fibrillation - a preliminary report.
AB  - INTRODUCTION: Atrial fibrillation (AF) is a frequently encountered complication
      after coronary artery bypass grafting (CABG), but its underlying mechanisms are
      still unclear. The natriuretic peptides have been reported as markers for
      predicting the occurrence of postoperative AF. This study evaluates whether the
      ScaI ANP gene polymorphisms predict the occurrence of postoperative AF. MATERIAL
      AND METHODS: A prospective study of 203 consecutive patients with coronary artery
      disease undergoing elective CABG was undertaken for atrial natriuretic peptide
      (ANP) ScaI gene polymorphism. Several perioperative data were analysed.
      Postoperative AF was defined as lasting for at least 15 min, confirmed by 12-lead
      ECG and occurring within 6 postoperative days. The ScaI polymorphism of the ANP
      gene was determined by polymerase chain reaction (PCR). Size-dependent separation
      of the PCR products on a polyacrylamide gel was followed by staining with
      ethidium bromide. RESULTS: The total frequency of AF was 19.7%. The frequencies
      of ScaI ANP gene polymorphisms were as follows: A1A1 4.90%, A1A2 59.60% and A2A2
      35.46%. In order to assess the hypothesis that the A2 allele is a marker of
      increased risk of postoperative atrial fibrillation, the odds ratio (OR) was
      calculated: A2 vs. non-A2, OR = 0.98 (0.23-4.1), p = 0.97, which was not
      significant. The odds ratios for A2A2 and A1A1 were not significant either: A2A2
      vs. non-A2A2, OR = 1.11 (0.54-2.29), p = 0.76, and A1A1 vs. non-A1A1, OR = 1.17
      (0.23-5.92), p = 0.84. CONCLUSIONS: ANP genotype did not predispose to the
      incidence of "new-onset" AF.

PMID- 28507572
TI  - Transient dilutional acidosis but no lactic acidosis upon cardiopulmonary bypass
      in patients undergoing coronary artery bypass grafting.
AB  - INTRODUCTION: Dilutional acidosis may result from the introduction of a large
      fluid volume into the patients' systemic circulation, resulting in a considerable
      dilution of endogenous bicarbonate in the presence of a constant carbon dioxide
      partial pressure. Its significance or even existence, however, has been strongly
      questioned. Blood gas samples of patients operated on with standard
      cardiopulmonary bypass (CPB) were analyzed in order to provide further evidence
      for the existence of dilutional acidosis. MATERIAL AND METHODS: Between 07/2014
      and 10/2014, a total of 25 consecutive patients scheduled for elective isolated
      coronary artery bypass grafting with CPB were enrolled in this prospective
      observational study. Blood gas samples taken regularly after CPB initiation were
      analyzed for dilutional effects and acid-base changes. RESULTS: After CPB
      initiation, hemoglobin concentration dropped from an average initial value of
      12.8 g/dl to 8.8 g/dl. Before the beginning of CPB, the mean value of the
      patients' pH and base excess (BE) value averaged 7.41 and 0.5 mEq/l,
      respectively. After the onset of CPB, pH and BE values significantly dropped to a
      mean value of 7.33 (p < 0.0001) and -3.3 mEq/l (p < 0.0001), respectively, within
      the first 20 min. In the following period during CPB they recovered to 7.38 and 
      0.5 mEq/l, respectively, on average. Patients did not show overt lactic acidosis.
      CONCLUSIONS: The present data underline the general existence of dilutional
      acidosis, albeit very limited in its duration. In patients undergoing coronary
      artery bypass grafting it seems to be the only obvious disturbance in acid-base
      homeostasis during CPB.

PMID- 28507571
TI  - Transcatheter paravalvular leak closure and hemolysis - a prospective registry.
AB  - INTRODUCTION: Paravalvular leak (PVL) related to a surgical prosthetic valve may
      be associated with clinically significant hemolysis. The influence of
      transcatheter PVL closure (TPVLC) on hemolysis remains uncertain. MATERIAL AND
      METHODS: The prospective registry included patients undergoing TPVLC due to PVL
      related heart failure and/or hemolysis. Procedural data, laboratory markers of
      hemolysis and heart failure status were recorded at baseline, discharge and at 1-
      and 6-month follow-up. RESULTS: Of 116 patients from all those qualified for
      TPVLC, 79 fulfilled the inclusion/exclusion criteria. Hemolysis was significantly
      more frequent in patients with mitral location of PVL and with calcifications in
      its channel. After TPVLC prompt reduction of lactate dehydrogenase activity
      (617.0 (342.0-899.0) vs. 397 (310.0-480.5) IU/l, p < 0.05) and gradual resolution
      of anemia (hemoglobin (HGB) 11.7 (10.4-13.8) vs. 13.4 (12.9-13.8) g%, p < 0.05)
      over 6 months were noted. Effective closure of PVL (> 90% reduction of PVL cross
      sectional area) resulted in a more prominent increase of red blood cell count and
      HGB than in patients with residual regurgitation. The TPVLC-related exacerbation
      of hemolysis was recorded in 14 patients. Its risk was aggravated by presence of
      significant hemolysis at baseline or residual flow either by a partially
      uncovered channel or across the occluder. Reduction of hemolysis after successful
      TPVLC was sustained in 6-month follow-up. CONCLUSIONS: Risk factors for PVL
      related hemolysis were the presence of calcifications in the defect and mitral
      location of PVL. The TPVLC effectively reduced hemolysis if at least 90%
      reduction of PVL cross sectional area was achieved. The effect was sustained in 6
      month follow-up. Incomplete closure of PVL may increase the magnitude of
      hemolysis after TPVLC, but it occurred rarely.

PMID- 28507573
TI  - Admission D-dimer testing for differentiating acute aortic dissection from other
      causes of acute chest pain.
AB  - INTRODUCTION: The present study aims to evaluate the utility of D-dimer testing
      for differentiating the causes of acute chest pain, including acute aortic
      dissection (AAD), pulmonary embolism (PE), acute myocardial infarction (AMI),
      unstable angina (UA), and other uncertain diagnoses of chest pain. MATERIAL AND
      METHODS: Consecutive patients admitted for acute chest pain within 24 h from
      symptom onset were enrolled prospectively, and plasma D-dimer levels were
      measured on admission. Diagnoses of AAD, PE, AMI, and UA were confirmed by
      standard methods. RESULTS: A total of 790 patients were enrolled, including 202
      AAD, 43 PE, 315 AMI, 136 UA, and 94 cases of other uncertain diagnoses. D-dimer
      levels were significantly higher in patients with AAD and PE than in those with
      AMI, UA, and other uncertain diagnoses (p < 0.001), but they were comparable
      between patients with AAD and PE (p = 0.065). Moreover, patients with type A AAD
      had higher D-dimer levels than those with type B AAD (p = 0.022). Receiver
      operating characteristic (ROC) curve analysis showed that a D-dimer level < 0.5
      ug/ml was a good predictor for ruling out AAD, with a sensitivity of 94.0% and a
      specificity of 56.8%. At a cut-off level of 0.5 ug/ml, the negative and positive
      likelihood ratios were 0.10 and 2.18, respectively, with a positive predictive
      value of 42.6% and a negative predictive value of 96.6%. CONCLUSIONS: The D-dimer
      level within 24 h after symptom onset might be helpful for differentiating AAD
      from other causes of chest pain.

PMID- 28507574
TI  - Blood groups and acute aortic dissection type III.
AB  - INTRODUCTION: Acute aortic type III dissection is one of the most catastrophic
      events, with in-hospital mortality ranging between 10% and 12%. The majority of
      patients are treated medically, but complicated dissections, which represent 15%
      to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR).
      For the best outcomes adequate blood transfusion support is required. Interest in
      the relationship between blood type and vascular disease has been established.
      The aim of our study is to evaluate distribution of blood groups among patients
      with acute aortic type III dissection and to identify any kind of relationship
      between blood type and patient's survival. MATERIAL AND METHODS: From January
      2005 to December 2014, 115 patients with acute aortic type III dissection were
      enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia
      and retrospectively analyzed. Patients were separated into two groups. The
      examination group consisted of patients with a lethal outcome, and the control
      group consisted of patients who survived. RESULTS: The analysis of the blood
      groups and RhD typing between groups did not reveal a statistically significant
      difference (p = 0.220). CONCLUSIONS: Our results indicated no difference between
      different blood groups and RhD typing with respect to in-hospital mortality of
      patients with acute aortic dissection type III.

PMID- 28507576
TI  - Red blood cell distribution width in patients with limb, chest and head trauma.
AB  - INTRODUCTION: This study investigated the values of red blood cell distribution
      width (RDW), an emerging and independent predictor of morbidity and mortality, in
      patients with limb, chest and head trauma. MATERIAL AND METHODS: The study sample
      consisted of all patients who attended the emergency department (ED) of the
      University Hospital of Parma for limb, chest and head traumas requiring admission
      to hospital wards during the year 2014. The controls consisted of outpatients
      living in the same geographical area and undergoing routine laboratory testing
      for health check-up. RESULTS: The final study sample consisted of 290 patients
      with limb (n = 97), chest (n = 49) or head (n = 144) trauma and 967 outpatients.
      Significantly increased RDW values at admission were observed in all trauma
      patients compared with controls. Although the frequency of increased RDW (>
      14.6%) was higher in all trauma patients than in controls, a subanalysis revealed
      that increased RDW values were significantly more frequent in patients with head
      trauma than in controls, but not in those with limb or chest trauma. In
      multivariate analysis, a significant association was found between head trauma
      and hemoglobin (p < 0.001) or RDW (p = 0.005). Head trauma patients had a ~3-fold
      higher likelihood of increased RDW values than controls. The negative and
      positive predictive values of increased RDW for predicting the presence of head
      trauma were 0.90 (95% CI: 0.88-0.92) and 0.24 (95% CI: 0.19-0.30). CONCLUSIONS:
      The results of this study highlight that RDW is increased in patients admitted to
      the ED with head trauma.

PMID- 28507575
TI  - Association between telomere length and complete blood count in US adults.
AB  - INTRODUCTION: Telomere length (TL) is related to age-related health outcomes, but
      little is known about the relationship between TL and complete blood count (CBC)
      parameters. We aimed to determine the relationship between TL and CBC in a sample
      of healthy US adults. MATERIAL AND METHODS: Participants in the National Health
      and Nutrition Examination Survey (NHANES) recruited between 1999 and 2002 who had
      essential data on total CBC and TL were studied. We computed age- and race
      adjusted mean values for total CBC using analysis of covariance (ANCOVA). All
      statistical analyses accounted for the survey design and sample weights by using
      SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY). RESULTS: Of the 8892 eligible
      participants, 47.8% (n = 4123) were men. The mean age was 41.8 years overall,
      41.0 years in men and 42.6 in women (p = 0.238). The sex-stratified ANCOVA showed
      no significant difference in the total CBC across TL quartiles (all p > 0.05) in
      both sexes. In the adjusted model, there was a significant negative relationship
      with monocyte count (beta = -0.051, 95% CI: -0.422; -0.142), mean cell hemoglobin
      (beta = -0.051, 95% CI: -0.038; -0.011) and red cell distribution width (beta = 
      0.031, 95% CI: -0.054; -0.003), while there was a significant positive
      relationship with basophil ratio (beta = 0.046, 95% CI: 0.049-0.171).
      CONCLUSIONS: These results support the possibility that telomere attrition may be
      a marker for reduced proliferative reserve in hematopoietic progenitor cells.

PMID- 28507577
TI  - Peritoneal lavage examination as a prognostic tool in cases of gastric cancer.
AB  - INTRODUCTION: Peritoneal tumor seeding is a common form of recurrence after
      gastric cancer surgery. The finding of free tumor cells and/or elevation of tumor
      markers in the peritoneal fluid could predict intraperitoneal tumor recurrence.
      The results of these examination can be used for indication of aggressive
      treatment modalities such as hyperthermic intraperitoneal chemotherapy (HIPEC).
      MATERIAL AND METHODS: We have operated on 105 patients suffering from gastric
      cancer. The control group consisted of 12 patients without malignant disease.
      Peritoneal lavage fluid or ascites was collected immediately after laparotomy and
      examined by cytology and biochemistry (levels of carcinoembryonic antigen (CEA)
      and Ca 19-9). Sensitivity, specificity, stage correlation and overall survival
      were observed. RESULTS: Elevation of tumor markers or the finding of free
      intraperitoneal tumor cells predicts recurrence. The prognosis of these patients
      is same as in stage IV TNM classification with median survival time less than 1
      year (p = 0.713). Patients with negative cytology have median survival time 5
      years contrary to them with positive cytology (p < 0.001). Sensitivity of the
      cytology was 34% and specificity was 85%. Sensitivity of biochemistry was 53%
      (combination of both markers) and specificity was 100%. CONCLUSIONS: This study
      confirms the importance of peritoneal fluid examination for the prognosis. We
      cannot recommend routine use as an indicator for HIPEC due to low sensitivity,
      but the result of cytological examination is an independent factor for patient
      survival.

PMID- 28507578
TI  - Lobular carcinoma in situ of the breast - correlation between minimally invasive
      biopsy and final pathology.
AB  - INTRODUCTION: Lobular carcinoma in situ (LCIS) is regarded as a non-obligate
      precursor of invasive breast cancer (IBC). Hence, the optimal management of LCIS
      found on minimally invasive breast biopsy remains a subject of debate. The aim of
      this study was to evaluate the correlation of biopsy findings with postoperative
      histology and to identify risk factors for upstaging to IBC. MATERIAL AND
      METHODS: Twenty-seven patients with pure LCIS diagnosed on image-guided biopsy
      (vacuum-assisted or core-needle) underwent subsequent surgery. Clinical,
      radiological and histological features were compared to the final pathology after
      surgical excision. RESULTS: Median age of patients was 56 years while median size
      of LCIS was 15 mm. Final examination demonstrated IBC foci in 29.6% of lesions.
      Upstaged patients were younger and had larger lesions but without statistical
      significance (p = 0.07 and p = 0.09, respectively). Palpable tumours (p =
      0.0004), BIRADS 5 lesions (p = 0.0001), masses (p = 0.016) and pleomorphic LCIS
      (p = 0.0001) had a significantly increased rate of upstaging. Guidance of the
      procedure (ultrasound vs. stereotactic) was significantly associated with the
      upstaging risk (p = 0.016), while the importance of the biopsy technique (core
      needle vs. vacuum-assisted) was not confirmed (p = 0.37). After excluding
      pleomorphic LCIS and mass-forming classic LCIS, there was no risk of upstaging
      for lesions with BIRADS 4 mammographic abnormalities. CONCLUSIONS: Pleomorphic
      histology, mass formation and BIRADS 5 category reflect more aggressive behaviour
      of LCIS and identify patients who need subsequent surgery. For other patients,
      close follow-up could be a safe alternative.

PMID- 28507579
TI  - Assessment of concentrations of sTRAIL ligand and its receptors sTRAIL-R1 and
      sTRAIL-R2 - markers monitoring the course of the extrinsic pathway of apoptosis
      induction: potential application in ovarian cancer diagnostics.
AB  - INTRODUCTION: TNF-related apoptosis-inducing ligand (TRAIL) together with its
      receptors are involved in activation of the extrinsic pathway of apoptosis. Due
      to the special role of the apoptosis pathway in pathogenesis of ovarian cancers,
      the aim of the study was to assess concentrations of sTRAIL, sTRAIL-R1 and sTRAIL
      R2 in serum of affected women. MATERIAL AND METHODS: The study group included 85
      women with diagnosed ovarian tumors: 35 women with ovarian serous cystadenoma, 15
      women with ovarian teratoma and 35 women with serous cystadenocarcinoma. The
      control group consisted of 30 healthy women. Concentrations of studied parameters
      were measured by ELISA methods. RESULTS: Serum levels of all studied parameters
      were higher in serum of women with ovarian tumors than in the controls, but their
      concentrations varied depending on the clinical diagnosis. The highest
      concentration of TRAIL was found in serum of women with ovarian cancer, the
      highest sTRAIL-R1 level in serum of women with ovarian mature teratoma, and the
      highest sTRAIL-R2 level in serum of women with ovarian serous cystadenoma.
      CONCLUSIONS: The state of immunosuppression accompanying neoplastic disease
      depends on the extrinsic pathway of apoptosis induction in the TRAIL/TRAIL-R
      system. Determination of TRAIL-R1 and TRAIL-R2 levels may prove to be useful in
      ovarian tumor differential diagnostics, which requires further research.

PMID- 28507580
TI  - Impact of antenatal oxytocin infusion on neonatal respiratory morbidity
      associated with elective cesarean section.
AB  - INTRODUCTION: This study was designed to estimate respiratory morbidity
      associated with elective cesarean section (ECS) and to determine the effect of
      antenatal oxytocin exposure on this morbidity. MATERIAL AND METHODS: Nine hundred
      and sixty-five neonates >= 37 weeks' gestation delivered by cesarean section
      during 1 year were included in this retrospective study and classified into two
      groups according to oxytocin exposure before cesarean deliveries. Respiratory
      morbidity for each group was recorded and statistically analyzed. RESULTS:
      Transient tachypnea of newborn (TTN) was significantly more frequent in group II
      (ECS group) than in group I (cesarean section after oxytocin exposure) (8.19% vs.
      2.92%; respectively, p = 0.0006). Mechanical ventilation, continuous positive
      airway pressure (CPAP) and oxygen therapy were significantly more frequent in
      group II than in group I (1.78%, 2.14% and 4.28% versus 0.44%, 0.58% and 1.46%,
      respectively; p = 0.039, and p = 0.033 and p = 0.009, respectively). The number
      of newborns admitted to the neonatal unit and neonatal intensive care unit (NICU)
      was significantly higher in group II than in group I (6.41% and 2.14% vs. 2.05%
      and 0.58%, respectively; p = 0.001 and p = 0.033, respectively). Surfactant,
      fluid therapies and parenteral nutrition were significantly more frequent in
      group II than in group I (2.14%, 4.28% and 2.49% vs. 0.15%, 1.46% and 0.73%,
      respectively; p = 0.001, p = 0.009 and p = 0.02, respectively). CONCLUSIONS:
      Neonatal respiratory morbidity associated with ECS significantly decreased after
      antenatal oxytocin exposure. A significant reduction of neonatal respiratory
      morbidity would be achieved if ECS were performed after 39 weeks' gestation.

PMID- 28507581
TI  - Long-term outcomes in children with chronic kidney disease stage 5 over the last
      40 years.
AB  - INTRODUCTION: We evaluated outcomes in children with chronic kidney disease stage
      5 (CKD 5) treated in the first pediatric dialysis unit in Poland during 1973
      2012. MATERIAL AND METHODS: The retrospective analysis included 208 children with
      CKD 5 undergoing renal replacement therapy (RRT), stratified into four decades of
      treatment: 1973-1982, 1983-1992, 1993-2002, and 2003-2012. RESULTS: The most
      common causes of CKD 5 included glomerulonephritis in 27.4% and pyelonephritis
      secondary to urinary tract anomalies in 25.5% of children. Among 208 children,
      172 (82.7%) survived and 17.3% died. Kidney transplantation (KTx) was performed
      in 47.6% of children, including pre-emptive KTx in 1.92% of children. Chronic
      dialysis was continued in 34.1% of children, and RRT was withdrawn in 1%. The
      overall mortality rate was 6.2 per 100 patient-years, and 3-year survival was
      83.9%. The highest mortality rate of 23.4 per 100 patient-years was observed
      among children in whom RRT was initiated in 1973-1982, with subsequent reduction
      of the mortality rate to 4.5 and 2.1 per 100 patient-years in 1993-2002 and 1983
      1992 respectively. No deaths were noted after 2002. Cardiovascular problems were
      the most common cause of death, found in 36.1% of patients (p < 0.01). Identified
      risk factors for mortality included young age, low residual diuresis, anemia at
      the time of RRT initiation, and hypertriglyceridemia and hypoalbuminemia during
      RRT. CONCLUSIONS: In years 1973-2012 significant improvement in prognosis among
      children with CKD 5 was achieved. Identified predictors of mortality included
      young age at initiation of RRT, low residual diuresis, anemia and
      hypertriglyceridemia.

PMID- 28507582
TI  - Decreased activity of butyrylcholinesterase in blood plasma of patients with
      chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Butyrylcholinesterase (BChE) is involved in the metabolism of
      endogenous lipids and xenobiotics, such as esters of carboxylic or phosphoric
      acids. Butyrylcholinesterase activity is associated with both inflammation and
      oxidative stress. Changes in the activity of this enzyme have been observed in
      various diseases such as liver cirrhosis, diabetes, neurodegenerative disease and
      others. MATERIAL AND METHODS: The study involved 30 patients with chronic
      obstructive pulmonary disease (COPD) and 18 healthy subjects. The COPD patients
      were divided according to the severity of the disease by applying the
      classification of COPD based on GOLD standards for forced expiratory volume in 1
      s (FEV1) and the FEV1/forced expiratory volume (FVC) ratio. The control group
      comprised blood samples collected from healthy subjects without concomitant
      diseases related to the respiratory system. Butyrylcholinesterase activity, lipid
      peroxidation and total antioxidant capacity (TAC) were determined in the blood
      plasma. RESULTS: A significant (p < 0.05) decrease in the activity of BChE,
      associated with an increase in lipid peroxidation and a decrease in the total
      antioxidant capacity, was observed in blood plasma of patients with chronic
      obstructive pulmonary disease. CONCLUSIONS: The study shows for the first time
      that activity of BChE in the blood plasma of patients diagnosed with chronic
      obstructive pulmonary disease is considerably reduced compared with healthy
      subjects. These changes were accompanied by a decrease of TAC and an increase of
      lipid peroxidation, which suggests that they may be related to the oxidative
      stress induced by COPD disease.

PMID- 28507583
TI  - Intravenous drug use - an independent predictor for HCV genotypes 3 and 4
      infection among HIV/HCV co-infected patients.
AB  - INTRODUCTION: About one quarter of human immunodeficiency virus (HIV) infected
      persons in Serbia have also been found to be hepatitis C virus (HCV) co-infected.
      In the general population, HCV genotype 1 has been shown to be the most prevalent
      one. Here, we present the first study on the distribution of HCV genotypes among
      HIV/HCV co-infected patients in Serbia, in relation to epidemiological and
      clinical features. MATERIAL AND METHODS: The study included HIV/HCV co-infected
      and a group of HCV mono-infected patients in the period 1998-2012, with
      collection of epidemiological, clinical, and behavioral data using a standardized
      questionnaire. The HCV genotyping to the level of pure genotype was performed by
      reverse hybridization. RESULTS: Intravenous drug use (IDU) was found to be
      significantly more prevalent among the co-infected patients (p < 0.01). HCV
      genotype 1 was detected in 87% of patients with mono-infection, compared to 46.3%
      of patients with co-infection (p < 0.01); genotypes 3 and 4 were significantly
      more common among co-infected patients (6% and 5%, vs. 27% and 25%,
      respectively). Multivariate logistic regression confirmed IDU, infection with non
      1 HCV genotype and HCV viral load over 5 log to be predictors of HIV co
      infection. CONCLUSIONS: The HCV genotypes 3 and 4 were found to be significantly
      more prevalent among HIV/HCV co-infected patients in Serbia, compared to HCV mono
      infected patients, but also more prevalent compared to the European HIV/HCV co
      infected cohort. History of IDU represents an independent predictor of HCV
      genotypes 3 and 4 infection, with important implications for treatment.

PMID- 28507584
TI  - Effects of adenosine receptor antagonists in MPTP mouse model of Parkinson's
      disease: mitochondrial DNA integrity.
AB  - INTRODUCTION: In Parkinson's disease (PD), compelling data indicate a functional
      link between adenosine/dopamine receptors and the progression of the
      neurodegenerative process. The present study was carried out to evaluate the
      effect of the non-selective adenosine receptor (ADR) antagonist caffeine, as well
      as the selective antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an
      ADRsA1 antagonist, and ((E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7
      dihydro-1H-purine-2,6-dione) (KW-6002), an ADRsA2A antagonist, on the prevention
      of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in
      mice. MATERIAL AND METHODS: Mice were allocated to five groups: group I - control
      group; group II: MPTP group, received four injections of MPTP (20 mg/kg, i.p.) at
      2 h intervals; groups III, IV, V: received MPTP and i.p. caffeine (20 mg/kg/day)
      or DPCPX (5 mg/kg/day) or KW-6002 (10 mg/kg/day) starting one week before MPTP
      injection and continuing for 2 weeks. RESULTS: Therapy with caffeine or KW-6002
      not only led to the reversibility of movement dysfunction and increased the
      concentrations of dopamine and ATP levels (p < 0.05), but also, ameliorates the
      dopaminergic neuron loss and restored the mtDNA and nDNA integrity (p < 0.05).
      Furthermore, in passive avoidance test, caffeine and DPCPX significantly (p <
      0.05) reversed the MPTP-induced memory deficits, whereas the specific ADRsA2A
      antagonist did not. CONCLUSIONS: The current results provide evidence that
      blockade of both ADRsA1 and ADRsA2A has therapeutic implications in alleviating
      MPTP-induced motor and cognitive dysfunction and might be a promising candidate
      for treatment of PD.

PMID- 28507587
TI  - An unusual etiology of torsade de pointes-induced syncope.

PMID- 28507585
TI  - CTGF upregulation correlates with MMP-9 level in airway remodeling in a murine
      model of asthma.
AB  - INTRODUCTION: Connective tissue growth factor (CTGF) mediates hypertrophy,
      proliferation, and extracellular matrix synthesis. Matrix metalloproteinase (MMP)
      plays a role in airway extracellular matrix remodeling. The correlation between
      CTGF and MMP in airway remodeling of asthma was unknown. This study investigated
      lung CTGF expression and its correlation with MMP and airway structural changes
      in a murine model of asthma. MATERIAL AND METHODS: Female BALB/c mice were
      sensitized and challenged by intraperitoneal injections and intranasal phosphate
      buffered saline (PBS) or ovalbumin (OVA). Airway responsiveness and serum OVA
      specific IgE were measured. Airway structural changes were quantified by
      morphometric analysis. Differential cell counts and MMP-2, MMP-9, and tissue
      inhibitor of metalloproteinase (TIMP)-1 were evaluated in bronchoalveolar lavage
      fluid (BALF). Lung CTGF was determined by Western blot. RESULTS: Serum OVA
      specific IgE level and airway responsiveness in enhanced pause (Penh) is
      significantly higher in sensitized mice challenged with OVA compared to PBS
      challenged mice. MMP-2, MMP-9, and TIMP-1 in BALF were significantly higher in
      OVA mice. Airway structural changes of animals' lungs with OVA challenge showed
      increased thickness of the smooth muscle layer and numbers of Goblet cells and
      inflammatory cells and eosinophils near airways and perivascular areas. Lung CTGF
      expression significantly increased in OVA-challenged mice. CTGF expressions
      positively correlated with MMP-9 (r = 0.677, p < 0.05), TIMP-1 (r = 0.574, p <
      0.05) and thickness of the smooth muscle layer (r = 0.499, p < 0.05).
      CONCLUSIONS: This study indicates that CTGF upregulation correlates with MMP-9,
      probably involved in the pathogenesis of airway remodeling of asthma.

PMID- 28507588
TI  - Henoch-Schonlein purpura in a pediatric patient with lupus.

PMID- 28507589
TI  - Successful treatment of a 20-year nonhealing venous leg ulcer in a patient with
      systemic lupus erythematosus.

PMID- 28507586
TI  - Neutrophil elastase stimulates MUC5AC expression in human biliary epithelial
      cells: a possible pathway of PKC/Nox/ROS.
AB  - INTRODUCTION: Bacterial infection and bile flow retardation form a vicious cycle
      which promotes stone formation and recurrence, and it seems that mucin
      overexpression plays an important role in this process. However, the mechanism of
      increased mucus secretion in the biliary tract by bacterial infection and its
      treatment remain unclear. MATERIAL AND METHODS: Human biliary epithelial cells
      were induced by neutrophil elastase (NE), and H2O2 production in the cell
      supernatants was detected by a specific kit, and then cells were pretreated with
      a H2O2 inhibitor, and expression of MUC5AC was detected by real-time polymerase
      chain reaction (PCR), Western blot, and immunohistochemistry. Moreover, selective
      PKC and Nox inhibitors, apocynin and bisindolylmaleimide I, were used to pretreat
      cells and detect H2O2, MUC5AC mRNA and protein expression. Then, we pretreated
      cells with selective inhibitors or NE, and detected transforming growth factor
      alpha (TGF-alpha) using an ELISA kit. RESULTS: H2O2 production increased in an NE
      dose-dependent manner (p < 0.001), and NE upregulated MUC5AC expression at both
      mRNA and protein levels, while DMTU, could reduce this high expression (p < 0.01
      at mRNA level, p < 0.001 at grey analysis for western blot and p < 0.01 at mean
      density for immunohistochemical staining at protein level). Moreover, apocynin
      and bisindolylmaleimide I could reduce the H2O2 production stimulated by NE (p <
      0.05), and reduce MUC5AC high expression (p < 0.01 at mRNA level, p < 0.001 at
      both grey analysis for western blot and mean density for immunohistochemical
      staining at protein level). In addition, NE induced TGF-alpha production, and any
      of the three selective inhibitors could reduce it (p < 0.05). CONCLUSIONS: NE
      induced reactive oxygen species participated in the upregulation of MUC5AC
      production. Moreover, protein kinase C and NADPH oxidase (Nox) regulate MUC5AC
      production in NE-challenged human biliary epithelial cells.

PMID- 28507590
TI  - Epithelioid hemangioendothelioma presenting as fever of unknown origin.

PMID- 28507592
TI  - Incarcerated recurrent inguinal hernia containing an acute appendicitis (Amyand
      hernia): an extremely rare surgical situation.

PMID- 28507591
TI  - Marginal zone B-cell lymphoma mimicking extramedullary plasmacytoma and the
      clinical outcome after treatment.

PMID- 28507593
TI  - Short Questionnaire for Workplace Analysis (KFZA): factorial validation in
      physicians and nurses working in hospital settings.
AB  - BACKGROUND: In recent years, there has been an increasing interest in
      psychosocial workplace risk assessments in Germany. One of the questionnaires
      commonly employed for this purpose is the Short Questionnaire for Workplace
      Analysis (KFZA). Originally, the KFZA was developed and validated for office
      workers. The aim of the present study was to examine the factorial validity of
      the KFZA when applied to hospital settings. Therefore, we examined the factorial
      structure of a questionnaire that contained all the original items plus an
      extension adding 11 questions specific to hospital workplaces and analyzed both,
      the original version and the extended version. METHODS: We analyzed questionnaire
      data of a total of 1731 physicians and nurses obtained over a 10-year period.
      Listwise exclusion of data sets was applied to account for variations in
      questionnaire versions and yielded 1163 questionnaires (1095 for the extended
      version) remaining for factor analysis. To examine the factor structure, we
      conducted a principal component factor analysis. The number of factors was
      determined using the Kaiser criterion and scree-plot methods. Factor
      interpretation was based on orthogonal Varimax rotation as well as oblique
      rotation. RESULTS: The Kaiser criterion revealed a 7-factor solution for the 26
      items of the KFZA, accounting for 62.0% of variance. The seven factors were
      named: "Social Relationships", "Job Control", "Opportunities for Participation
      and Professional Development", "Quantitative Work Demands", "Workplace
      Environment", "Variability" and "Qualitative Work Demands". The factor analysis
      of the 37 items of the extended version yielded a 9-factor solution. The two
      additional factors were named "Consequences of Strain" and "Emotional Demands".
      Cronbach's alpha ranged from 0.63 to 0.87 for these scales. CONCLUSIONS: Overall,
      the KFZA turned out to be applicable to hospital workers, and its content-related
      structure was replicated well with some limitations. However, instead of the 11
      factors originally proposed for office workers, a 7-factor solution appeared to
      be more suitable when employed in hospitals. In particular, the items of the KFZA
      factor "Completeness of Task" might need adaptation for the use in hospitals. Our
      study contributes to the assessment of the validity of this popular instrument
      and should stimulate further psychometric testing.

PMID- 28507594
TI  - Pain threshold reflects psychological traits in patients with chronic pain: a
      cross-sectional study.
AB  - BACKGROUND: Chronic pain enhances sensory sensitivity and induces the biased
      development of psychological traits such as depression and pain catastrophizing,
      leading to the formation of heterogeneous conditions. Fluctuations in the sensory
      related thresholds of non-injured sites (with normal peripheral tissue) in
      patients with chronic pain are thought to be related to central sensitization.
      The objectives of this study were to analyze the association between pain
      tolerance thresholds (PTTs) in non-injured sites and the psychological traits of
      patients with chronic pain and to evaluate the usefulness of PTT measures in
      assessments of pathological conditions related to chronic pain. METHODS: This
      study included 57 patients with chronic pain. The PTTs were measured in non
      injured sites with quantitative sensory testing (QST) with electrical stimulation
      and then classified with cluster analysis. The Short-Form McGill Pain
      Questionnaire was used to subjectively assess pain in the injured sites. The
      Minnesota Multiphasic Personality Inventory (MMPI) was used to assess the
      patients' psychological traits. RESULTS: Based on the cluster analysis of PTTs,
      the patients were classified into a High-Sensitivity group and an Others group
      consisting of the remaining patients. The results of the MMPI profiles showed
      that the High-Sensitivity group included significantly more patients with the
      Neurotic Triad pattern and no patients with the Conversion V pattern. The scores
      of the hypochondriasis and hysteria scales were significantly lower in the High
      Sensitivity group than in the Others group. CONCLUSIONS: This study indicated
      that patients with chronic pain can be classified according to PTTs in non
      injured sites and suggests that patients with High-Sensitivity have
      characteristic psychological traits. Assessment of PTTs in non-injured sites
      would be useful for evaluating the psychological condition of patients with
      chronic pain.

PMID- 28507596
TI  - Efficient whole-cell-catalyzing cellulose saccharification using engineered
      Clostridium thermocellum.
AB  - BACKGROUND: Cost-efficient saccharification is one of the main bottlenecks for
      industrial lignocellulose conversion. Clostridium thermocellum naturally degrades
      lignocellulose efficiently using the cellulosome, a multiprotein supermolecular
      complex, and thus can be potentially used as a low-cost catalyst for
      lignocellulose saccharification. The industrial use of C. thermocellum is
      restrained due largely to the inhibition of the hydrolysate cellobiose to its
      cellulosome. Although the supplementation of beta-glucosidase may solve the
      problem, the production of the enzymes greatly complicates the process and may
      also increase the cost of saccharification. RESULTS: To conquer the feedback
      inhibition and establish an efficient whole-cell catalyst for highly efficient
      cellulose saccharification, we constructed a recombinant strain of C.
      thermocellum ?pyrF::CaBglA which produced a secretory exoglucanase CelS-bearing
      heterologous BGL using a newly developed seamless genome editing system. Without
      the extra addition of enzymes, the relative saccharification level of
      ?pyrF::CaBglA was stimulated by over twofolds compared to its parent strain ?pyrF
      through a two-stage saccharification process with 100 g/L Avicel as the carbon
      source. The production of reducing sugars and the relative saccharification level
      were further enhanced to 490 mM and 79.4%, respectively, with increased cell
      density. CONCLUSIONS: The high cellulose-degrading ability and sugar productivity
      suggested that the whole-cell-catalysis strategy for cellulose saccharification
      is promising, and the C. thermocellum strain ?pyrF::CaBglA could be potentially
      used as an efficient whole-cell catalyst for industrial cellulose
      saccharification.

PMID- 28507595
TI  - Differential therapeutic effects of atomoxetine and methylphenidate in childhood
      attention deficit/hyperactivity disorder as measured by near-infrared
      spectroscopy.
AB  - BACKGROUND: The stimulant methylphenidate (MPH) and the nonstimulant atomoxetine
      (ATX) are the most commonly-prescribed pharmacological treatments for attention
      deficit/hyperactivity disorder (ADHD). However, the drug-specific mechanism of
      action on brain function in ADHD patients is not well known. This study examined
      differences in prefrontal hemodynamic activity between MPH and ATX in children
      with ADHD as measured by near-infrared spectroscopy (NIRS) using the Stroop color
      word task. METHODS: Thirty children with ADHD participated in the present study.
      We used 24-channel NIRS (ETG-4000) to measure the relative concentrations of
      oxyhemoglobin in the frontal lobes of participants in the drug-naive condition
      and those who had received MPH (n = 16) or ATX (n = 14) for 12 weeks.
      Measurements were conducted every 0.1 s during the Stroop color-word task. We
      used the ADHD RS-IV-J (Home Version) to evaluate ADHD symptoms. RESULTS:
      Treatment with either MPH or ATX significantly reduced ADHD symptoms, as measured
      by the ADHD RS-IV-J, and improved performance on the Stroop color-word task in
      terms of number of correct words. We found significantly higher levels of
      oxyhemoglobin changes in the prefrontal cortex of participants in the ATX
      condition compared with the values seen at baseline (pre-ATX). In contrast, we
      found no oxyhemoglobin changes between pre- and post-treatment with MPH.
      CONCLUSIONS: The present study suggests that MPH and ATX have differential
      effects on prefrontal hemodynamic activity in children with ADHD.

PMID- 28507597
TI  - Low adherence to national guidelines for proton-pump inhibitor prescription in
      patients receiving combination aspirin and anticoagulation.
AB  - BACKGROUND: Aspirin, when used with concurrent anticoagulation, increases the
      risk of gastrointestinal bleeding (GIB). Therefore, multisociety guidelines
      recommend prophylactic proton-pump inhibitors (PPIs) for patients receiving
      aspirin and anticoagulation. We aimed to determine rates and predictors of
      adherence to these recommendations. METHODS: All adult inpatients discharged from
      the hospital on aspirin and anticoagulation from July 2009 to June 2014 were
      retrospectively evaluated for PPI prescription on discharge instructions. We used
      univariate and multivariate logistic regression to test for predictors of PPI
      prescription. RESULTS: A total of 2422 patients were discharged on aspirin and
      anticoagulation; the mean age was 68 years and 53.2% were male; 42.2% were
      prescribed a PPI at discharge. On univariate analysis, factors associated with
      discharge PPI prescription included increased age (47.1% versus 37.9%), white
      race (47.3% versus 37.1-40.2%), higher aspirin dose (55.1% versus 39.4%), being
      married (46.2% versus 39.4%) and preadmission PPI use (96.6% versus 23.4%). On
      multivariate analysis, significant predictors of discharge PPI prescription were
      age 60-69 years [odds ratio (OR) 1.61] and 70-79 years (OR 1.48), and
      preadmission PPI use (OR 120.03). Lower odds of discharge PPI prescription
      included Medicaid (OR 0.55) or Medicare (OR 0.71) insurance, Spanish language (OR
      0.63), and lower dose aspirin (81 mg) (OR 0.40). CONCLUSIONS: A total of 42.2% of
      patients discharged on aspirin and anticoagulation were prescribed PPIs. Older
      age and preadmission PPI use were predictive of PPI prescription, while
      Medicaid/Medicare insurance, Spanish language, and lower dose aspirin decreased
      the likelihood of discharge PPI prescription. This creates an opportunity to
      improve primary GIB prevention through quality improvement interventions.

PMID- 28507598
TI  - Thalidomide induces clinical remission and mucosal healing in adults with active
      Crohn's disease: a prospective open-label study.
AB  - BACKGROUND: Thalidomide is effective in inducing and maintaining clinical
      remission in children and adolescents with refractory Crohn's disease (CD).
      However, little is known about the efficacy and safety of thalidomide for adult
      patients with CD. METHODS: We conducted a prospective open-label cohort study
      between January 2013 and April 2015. A total of 47 adult patients with active CD
      who were dependent/resistant or intolerant to corticosteroids and/or
      immunomodulators or biologics received 50-100 mg of thalidomide daily. Primary
      outcome was clinical remission evaluated at week 8. Endoscopic assessment was
      performed at week 24 and defined as endoscopic response (decrease in Crohn's
      Disease Endoscopic Index of Severity [CDEIS] score > 5 points from baseline CDEIS
      of 6 or more), complete endoscopic remission (CDEIS score < 3), and mucosal
      healing (MH) (no ulceration). RESULTS: A total of 47 adults with active CD were
      enrolled. The clinical remission rate was 14.9% and 23.4% at week 4 and week 8,
      but increased to 46.8% at week 12 and 53.2% at week 24 out of all the 47 patients
      included (intention-to-treat analysis). Altogether 32 patients consented and
      underwent ileocolonoscopy at week 24. The rate of endoscopic response and
      complete endoscopic remission were 68.4% and 43.8%. MH (no ulceration) was
      achieved in 28.1% of patients. Adverse events occurred in 27/47 (57.4%) patients
      but necessitated therapy discontinuation in only 5/47 (10.6%) of patients.
      CONCLUSIONS: Low-dose thalidomide was effective and tolerated for inducing and
      maintaining clinical remission in adult patients with active CD, but the optimal
      time frame for thalidomide to induce clinical remission may be longer than
      previously appreciated and is probably optimal at 12 weeks. MH could reasonably
      be achievable with thalidomide.

PMID- 28507599
TI  - Comparison of relapse-free survival in gastric neuroendocrine carcinoma (WHO
      grade 3) and gastric carcinoma.
AB  - BACKGROUND: We compared relapse-free survival (RFS) in gastric neuroendocrine
      carcinoma (WHO grade 3) and gastric carcinoma (GC). This is one of very few
      studies that compare the prognosis of poorly differentiated neuroendocrine
      carcinoma (WHO grade 3, G3 NEC) with that of GC. METHODS: Between 1996 and 2014,
      63 patients were diagnosed with G3 NEC of the stomach and 56 with gastric
      neuroendocrine tumors (NETs) with GC at Asan Medical Center in Seoul, Korea. We
      also randomly selected 762 patients diagnosed with GC between 1999 and 2008.
      RESULTS: Patients with G3 NEC tumors that invaded the muscularis propria or
      shallower had poorer RFS than those with GC of the same type, while G3 NEC that
      invaded the subserosa or deeper had similar RFS to GC of that type. Patients
      diagnosed with G3 NEC with N0 or N2 had poorer RFS than the corresponding
      patients with GC, while those who had G3 NEC with N1 or N3 had similar RFS to the
      corresponding patients with GC. G3 NEC patients had poorer RFS than well
      differentiated, moderately differentiated and poorly differentiated GC patients,
      while G3 NEC patients had similar RFS to that of those with signet ring cell
      carcinoma (SRC). In addition, patients with G3 NEC of stages I or IIa had poorer
      RFS than those with corresponding GC, while G3 NEC stage IIb or greater had
      similar RFS to the corresponding GC. CONCLUSIONS: Non-advanced G3 NEC showed
      poorer RFS than GC excluding SRC, while advanced G3 NEC has a similar RFS to that
      of GC without SRC. Therefore, we recommend that patients with non-advanced G3 NEC
      of the stomach be given a more aggressive treatment and surveillance than those
      with non-advanced GC excluding SRC.

PMID- 28507601
TI  - End of treatment RNA-positive/sustained viral response in an individual with
      acute hepatitis C virus infection treated with direct-acting antivirals.

PMID- 28507600
TI  - Insights into the role of the intestinal microbiota in colon cancer.
AB  - The intestinal microbiota consists of a dynamic organization of bacteria,
      viruses, archaea, and fungal species essential for maintaining gut homeostasis
      and protecting the host against pathogenic invasion. When dysregulated, the
      intestinal microbiota can contribute to colorectal cancer development. Though the
      microbiota is multifaceted in its ability to induce colorectal cancer, this
      review will focus on the capability of the microbiota to induce colorectal cancer
      through the modulation of immune function and the production of microbial-derived
      metabolites. We will also explore an experimental technique that is
      revolutionizing intestinal research. By elucidating the interactions of microbial
      species with epithelial tissue, and allowing for drug screening of patients with
      colorectal cancers, organoid development is a novel culturing technique that is
      innovating intestinal research. As a cancer that remains one of the leading
      causes of cancer-related deaths worldwide, it is imperative that scientific
      findings are translated into the creation of effective therapeutics to treat
      colorectal cancer.

PMID- 28507604
TI  - Health-related quality of life outcomes from botulinum toxin treatment in
      hemifacial spasm.
AB  - BACKGROUND: Although botulinum neurotoxin (BoNT) injections may alleviate
      involuntary muscle contractions in hemifacial spasm substantially, it is less
      clear whether the motor effect would translate into improvements of health
      related quality of life (HR-QoL). METHODS: In this open-label clinical
      observational study, we characterized outcomes on HR-QoL in terms of the EuroQol
      (EQ-5D-5L) from BoNT in a prospective cohort of patients with hemifacial spasm (n
      = 73). Additionally, we characterized appendicular motor and nonmotor signs on
      motor symptom improvement, depressive symptoms, pain and sleep quality. Patients
      were assessed at the end of a regular 3-month period from last injection
      (timepoint1) and 4 weeks after the reinjection of BoNT (timepoint2). RESULTS:
      Patients showed improved HR-QoL on the EQ-VAS (visual analogue scale) at
      timepoint2 compared with timepoint1. Moreover, we identified, that impairments in
      HR-QoL at timepoint1 correlated with life satisfaction and depressive symptoms,
      respectively. However, these associated variables did not predict the therapeutic
      effect. Instead, EQ-VAS at timepoint1 accounted for 34.5% of the variance of EQ
      VAS improvement expressed as the difference between timepoint2 and timepoint1.
      CONCLUSION: Our study supports HR-QoL improvements in hemifacial spasm and the
      value of generic HR-QoL measures to estimate therapeutic outcome. However, the
      findings should be considered descriptive, and future high quality trials are
      needed for confirmatory purposes in order to refine treatment referral in
      hemifacial spasm with respect to QoL.

PMID- 28507603
TI  - Fingolimod initiation in multiple sclerosis patients is associated with potential
      beneficial cardiovascular autonomic effects.
AB  - BACKGROUND: Fingolimod slows heart rate (HR) due to vagomimetic effects and might
      cause additional cardiovascular autonomic changes. While the time course of HR
      changes is well described, the extent and course of cardiovascular autonomic
      changes upon fingolimod initiation has not yet been evaluated. This study,
      therefore, intended to assess cardiovascular autonomic changes during the first 6
      h after fingolimod initiation. METHODS: In 21 patients with relapsing-remitting
      multiple sclerosis (RRMS), we recorded respiration (RESP), electrocardiographic
      RR interval (RRI), systolic and diastolic blood pressure (BPsys, BPdia) at rest,
      before and 0.5, 1, 2, 3, 4, 5, and 6 h after fingolimod initiation. We calculated
      parameters of total autonomic modulation [RRI standard deviation (RRI-SD), RRI
      coefficient of variation (RRI-CV), RRI-total powers], mainly sympathetic cardiac
      modulation [RRI low frequency (LF) powers], sympathetic BP modulation (BPsys-LF
      powers), parasympathetic modulation [square root of the mean squared difference
      of successive RRIs (RMSSD), RRI high frequency (HF) powers], sympatho-vagal
      cardiac balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). We compared
      parameters between the eight measurements [analysis of variance (ANOVA) or
      Friedman test with post-hoc analysis; significance: p < 0.05]. RESULTS: After
      fingolimod initiation, RESP, BPsys, and BPsys-LF powers remained unchanged while
      RRIs, RRI-CV, RRI-SD, RRI-total powers, RRI-LF powers, RMSSD, RRI-HF powers, and
      BRS increased after 1 h and rose to peak values occurring after 5, 1, 2, 2, 1, 4,
      4, and 4 h, respectively. After 3 h, BPdia had decreased significantly and was
      lowest after 5 h. RRI-LF/HF ratios decreased to a nadir after 4 h. CONCLUSIONS:
      The increases in parasympathetic and overall cardiac autonomic modulation and in
      BRS seen with fingolimod initiation are theoretically beneficial for the MS
      patient's cardiovascular system. However, long-term studies must show whether
      these effects persist or are attenuated (e.g. due to S1P1 receptor down
      regulation upon continued fingolimod therapy).

PMID- 28507605
TI  - Diclofenac potassium for oral solution (CAMBIA(r)) in the acute management of a
      migraine attack: clinical evidence and practical experience.
AB  - Migraine headache affects about 12% of Western populations and is the third most
      common disease worldwide (sixth in terms of disability). In 1993, triptans were
      introduced in the United States as a new treatment for managing migraine attacks,
      but their use is limited by lack of response and safety concerns in some
      patients. Treatment options for patients with migraine who fail or cannot
      tolerate triptans include switching to another medication or adding an adjunctive
      medication. Desirable characteristics reported by patients for acute treatment of
      migraine attacks include complete pain relief, fast onset of action, and no pain
      recurrence. Diclofenac is a nonsteroidal anti-inflammatory medication that has
      been established as effective for acute treatment of migraine by the American
      Headache Society based on available evidence. Diclofenac potassium for oral
      solution is rapidly absorbed, achieving maximal plasma concentrations in 15 min,
      which coincides with a rapid onset of effect. In a comparison of diclofenac
      potassium for oral solution with diclofenac potassium tablets, the solution
      achieved a significant reduction in headache intensity beginning at 15 min
      compared with 60 min for the tablet. Across randomized clinical trials,
      approximately 25% of patients were pain free 2 h after administration of
      diclofenac oral solution and the effects were maintained over a 24-h period.
      Diclofenac potassium for oral solution is well tolerated; the most common adverse
      events are dizziness and gastrointestinal complaints, with incidences similar to
      placebo. No serious adverse events have been reported in clinical trials of
      diclofenac potassium for oral solution in the acute treatment of migraine.
      Diclofenac oral solution may offer rapid and sustained pain relief for patients
      who do not achieve pain resolution with other medications. In addition, patients
      who experience central sensitization with allodynia may benefit from the
      cyclooxygenase-blocking activity of diclofenac, which is needed in this advanced
      phase of migraine.

PMID- 28507606
TI  - Transcription and chromatin determinants of de novo DNA methylation timing in
      oocytes.
AB  - BACKGROUND: Gametogenesis in mammals entails profound re-patterning of the
      epigenome. In the female germline, DNA methylation is acquired late in oogenesis
      from an essentially unmethylated baseline and is established largely as a
      consequence of transcription events. Molecular and functional studies have shown
      that imprinted genes become methylated at different times during oocyte growth;
      however, little is known about the kinetics of methylation gain genome wide and
      the reasons for asynchrony in methylation at imprinted loci. RESULTS: Given the
      predominant role of transcription, we sought to investigate whether transcription
      timing is rate limiting for de novo methylation and determines the asynchrony of
      methylation events. Therefore, we generated genome-wide methylation and
      transcriptome maps of size-selected, growing oocytes to capture the onset and
      progression of methylation. We find that most sequence elements, including most
      classes of transposable elements, acquire methylation at similar rates overall.
      However, methylation of CpG islands (CGIs) is delayed compared with the genome
      average and there are reproducible differences amongst CGIs in onset of
      methylation. Although more highly transcribed genes acquire methylation earlier,
      the major transitions in the oocyte transcriptome occur well before the de novo
      methylation phase, indicating that transcription is generally not rate limiting
      in conferring permissiveness to DNA methylation. Instead, CGI methylation timing
      negatively correlates with enrichment for histone 3 lysine 4 (H3K4) methylation
      and dependence on the H3K4 demethylases KDM1A and KDM1B, implicating chromatin
      remodelling as a major determinant of methylation timing. We also identified
      differential enrichment of transcription factor binding motifs in CGIs acquiring
      methylation early or late in oocyte growth. By combining these parameters into
      multiple regression models, we were able to account for about a fifth of the
      variation in methylation timing of CGIs. Finally, we show that establishment of
      non-CpG methylation, which is prevalent in fully grown oocytes, and methylation
      over non-transcribed regions, are later events in oogenesis. CONCLUSIONS: These
      results do not support a major role for transcriptional transitions in the time
      of onset of DNA methylation in the oocyte, but suggest a model in which sequences
      least dependent on chromatin remodelling are the earliest to become permissive
      for methylation.

PMID- 28507607
TI  - Gene variants in the FTO gene are associated with adiponectin and TNF-alpha
      levels in gestational diabetes mellitus.
AB  - BACKGROUND: Obesity may have a role in the development of gestational diabetes
      mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and
      obesity associated) gene have been associated with obesity. The aim of this study
      was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in
      women with GDM and their associations with maternal pre-pregnancy weight and body
      mass index, gestational weight gain and mediators of insulin resistance in GDM
      like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha),
      compared with healthy pregnant controls. METHODS: 80 women with GDM and 80 women
      with normal pregnancy were considered for the present study. Genotyping of
      selected SNPs in all study subjects was done using the Taq-Man assay and the
      adipokines and ghrelin were measured by immunoassays. Chi square test, odds
      ratios (OR) and their respective 95% confidence intervals were used to measure
      the strength of association between FTO SNPs and GDM. RESULTS: There was no
      association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying
      the risk alleles of the three SNPs had increased TNF-alpha, and decreased
      adiponectin levels; these associations remained significant after adjusting for
      pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was
      also associated with increased weight gain during pregnancy. CONCLUSIONS: The FTP
      SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the
      etiology of GDM in the studied ethnic group. However, these SNPs were associated
      with adiponectin and TNF-alpha concentrations in GDM subjects.

PMID- 28507608
TI  - Roles of fasting and postprandial blood glucose in the effect of type 2 diabetes
      on central arterial stiffness: a 5-year prospective community-based analysis.
AB  - BACKGROUND: Cardiovascular disease constitutes a major challenge for the health
      of community-dwelling population, it is essential to delay the development of
      atherosclerosis. However, long-term prospective studies analyzing the effect of
      type 2 diabetes (T2D) on central arterial stiffness are lacking, and roles of
      fasting and postprandial blood glucose (FBG and PBG) in this effect are
      controversial. Purpose of the current analysis was to investigate the effect of
      T2D on central arterial stiffness during the 5 years of follow-up, and explore
      whether both FBG and PBG were determinants of this effect in Chinese community
      dwelling population. METHODS: The current analysis involved 898 individuals with
      carotid-femoral pulse wave velocity (cfPWV) <=12 m/s. Central arterial stiffness
      was assessed by standard cfPWV at baseline and follow-up. RESULTS: Incidence of
      cfPWV >12 m/s was 21.3% (102 participants). Participants without T2D had an
      increase of cfPWV with a median of 0.6 m/s, whereas participants with T2D had an
      increase of cfPWV with a median of 1.2 m/s (p = 0.007). T2D had an independent
      effect on increased cfPWV in multivariate Logistic regression models (p < 0.05
      for all). Elevated levels of both FBG and PBG determined the independent effect
      on increased cfPWV in multivariate linear regression models (p < 0.05 for all).
      CONCLUSIONS: Type 2 diabetes had an independent effect on the development of
      central arterial stiffness in Chinese community-dwelling population. Both FBG and
      PBG should be responsible for the development of central arterial stiffness and
      treated as the targets of glycemic control.

PMID- 28507609
TI  - Depression and alexithymia on weight perception in patients with metabolic
      syndrome and type 2 diabetes.
AB  - BACKGROUND: Obesity's increasing follows decreased perception of weight status in
      obese persons, mainly female, undergoing age-related changes. OBJECTIVE: To study
      weight perception and psychological alterations associated to MS and T2DM.
      METHODS: 200 patients selected from Metabolic Syndrome Outpatient Clinic of
      University of Campinas. Instruments: Beck Depression and Beck Anxiety
      Inventories', Toronto Alexithymia Scale-26s, questionnaire and data from reports.
      Approved by Unicamp Research Ethic Committee. RESULTS: Patients aged 18-40 years
      perceived their weight higher than actual (A < D) (p = 0.0272), amongst untreated
      hypertensive (p = 0.037). >=41 years old patient's subdivided into A = D and A >
      D. A = D had 4.3 more chances to be alexithymic than A < D. 35% of A < D accepted
      their physical appearance, contrarily A = D (66%) and A > D (69%) (p = 0.0018).
      50% of A < D felt offended by social aggression due to their weight; A = D (20%)
      and A > D (34%) (p = 0.007). 3.6 more chances of A > D than A < D using anti
      hypertensive drugs (p = 0.021) (>=41 years old) and 3.5 more chances to perceive
      A = D (41-60 years old) (p = 0.023). A = D presented 3.8 more chances of
      depression than A < D and 4.3 more chances of alexithymia than A < D (62% of 41
      60 year-old patients with higher cholesterol, mainly LDL and hyper
      triglycerides). A = D with alexithymia, partially linked with higher cholesterol,
      suggests neuroinflammation due to hypertriglycerides. Females, who declared had
      been anteriorly made diet as treatment to lose weight were exactly those who
      perceived their weight A > D (45%, p = 0.0091). CONCLUSIONS: Age as a period of
      development, in which cultural influences occurs, was a factor in weight
      misperception. A < D and A > D were distinct in age, history of obesity and BMI.

PMID- 28507610
TI  - Improving Patient Safety in Hospitals through Usage of Cloud Supported Video
      Surveillance.
AB  - BACKGROUND: Patient safety in hospitals is of equal importance as providing
      treatments and urgent healthcare. With the development of Cloud technologies and
      Big Data analytics, it is possible to employ VSaaS technology virtually anywhere,
      for any given security purpose. AIM: For the listed benefits, in this paper, we
      give an overview of the existing cloud surveillance technologies which can be
      implemented for improving patient safety. MATERIAL AND METHODS: Modern VSaaS
      systems provide higher elasticity and project scalability in dealing with real
      time information processing. Modern surveillance technologies can prove to be an
      effective tool for prevention of patient falls, undesired movement and tempering
      with attached life supporting devices. Given a large number of patients who
      require constant supervision, a cloud-based monitoring system can dramatically
      reduce the occurring costs. It provides continuous real-time monitoring,
      increased overall security and safety, improved staff productivity, prevention of
      dishonest claims and long-term digital archiving. CONCLUSION: Patient safety is a
      growing issue which can be improved with the usage of high-end centralised
      surveillance systems allowing the staff to focus more on treating health issues
      rather that keeping a watchful eye on potential incidents.

PMID- 28507611
TI  - The Impact of Extended Typing On Red Blood Cell Alloimmunization in Transfused
      Patients.
AB  - BACKGROUND: Red blood cell (RBC) alloimmunization is still an actual problem in
      our transfusion practice. In 2011, in addition to the regular ABO/D blood group
      typing, phenotyping for Rh (C, c, E, e) and Kell antigens was introduced for
      blood donors and patients undergoing blood transfusion. Our aim was to evaluate
      the impact of the extended RBC typing and donor/recipient matching on the
      incidence of RBC alloimmunization. METHODS: A retrospective comparative study was
      conducted by reviewing RBC request records for about 36,000 patients transfused
      with RBC in the period from 2013 to 2015 in comparison to the similar study
      conducted on 47,000 transfused patients in the period from 2005 to 2008. Pre
      transfusion serologic testing data were retrieved for analysis. Blood samples
      with positive antibody screening and positive cross-match were further subjected
      to antibody identification. All the tests were performed using column
      agglutination technique (CAT) with ID-cards and reagents from DiaMed in both
      studies. RESULTS: Irregular RBC alloantibodies were detected in 116 (0.32%) out
      of 36,000 transfused patients. Multiple transfusions (15.8 units/patient) were
      given to 450 patients from which 79 (17.5%) had RBC allontibodies. The incidence
      of RBC alloimmunisation in the rest of the 35,550 transfused patients from which
      37 had RBC alloantibodies was 0.10%. A total of 117 alloantibodies were
      identified in 96 out of the 116 patients with irregular RBC antibodies. Their
      specificity was as fallows: anti-E (25.6%), -C (6.0%), -c (8.5%), -e (0.85%), -Cw
      (5.1%), -K (12.8%), -Fya (10.2%), -Fyb (2.5%), -Jka (7.7%), -Jkb (2.5%), -M
      (9.4%), -S (1.7%), -s (0.85%), -Lua (1.7%), -Leb (3.4%) and anti-Leb (0.85%).
      Multiple antibodies were identified in 22 of the transfused patients out of which
      15 (68.2%) received multiple transfusions. Anti-E was the most common antibody
      found in more of the 50% of the multiple antibody cases. CONCLUSIONS: The overall
      incidence of RBC alloimmunization in transfused patients decreased from 0.51%
      which was the estimated incidence for the period before the introduction of the
      extended RBC typing (2005-2008) to 0.32% (2013-2015). This is due to the
      decreased incidence of RBC alloimmunization in the multiply transfused patients
      from 33.9% to 17.5% respectively. The current frequency of anti-E (25.6%) and -K
      (12.8%) antibodies in transfused patients are significantly lower than their
      previous estimated frequencies of 30.4% and 24.0% respectively, as well as the
      overall frequency of RBC antibodies to Rh+Kell antigens which decreased from
      72.4% to 53.8%. Extended donor-recipient matching for C, c, E, e and Kell
      antigens has proved a beneficial effect on the incidence of RBC alloimmunization
      in multiply transfused patients.

PMID- 28507612
TI  - Pattern of Injuries in Fatal Motorcycle Accidents Seen in Lagos State University
      Teaching Hospital: An Autopsy-Based Study.
AB  - BACKGROUND: Deaths from motorcycle accident injuries have remained a major public
      health issue in Nigeria over the years. AIM: The study is to determine the age
      and gender distribution of the victims and to identify the cause of death and the
      anatomical pattern of injuries seen. METHODOLOGY: This is a 5-year autopsy-based
      study of all motorcycle accident deaths seen in Lagos State University Teaching
      Hospital between December 2009 and November 2014. The data were retrieved from
      autopsy reports, hospital case notes extracts from police diary and were analysed
      using SPSS version 20. RESULTS: Motorcycle accidents accounted for 156 (2.8%) of
      all the autopsies done (5,661), and 156 (18.4%) of all Road Traffic Accidents
      (RTA) autopsies (849) performed over the study period, with a male: female ratio
      of 6:1. The peak age of victims was 31-40 years (30.9%). Head injuries accounted
      for most (41.4%) of the injuries seen, and the majority of the victims died of
      craniocerebral injury 53 (50.7%). CONCLUSION: This study showed that males in the
      fourth decade of life are the major victims of motorcycle accident death. The
      majority of the victims were the rider of the motorcycle. Most of them died of
      the craniocerebral injury.

PMID- 28507613
TI  - Correlation between Soil-Transmitted Helminths Infection and Serum Iron Level
      among Primary School Children in Medan.
AB  - BACKGROUND: The latest estimates indicate that more than 2 billion people
      worldwide are infected by Soil-Transmitted Helminths (STH). The burden of STH
      infection is mainly attributed to the chronic effect on health and quality of
      life of those infected. It is also contributed to micronutrient deficiencies such
      as iron-deficiency anaemia. The prevalence of worm infection in Public Primary
      School students in Medan was quite high (40.3%), and 33.3% was anaemic in the
      latest study. AIM: To determine the correlation between STH infection with serum
      iron (SI) level on primary school children, as well as to determine the
      prevalence of SI level and worm infection, and the type of worm that infects the
      most of them. METHODS: This study was conducted in the cross-sectional method.
      Consecutive sampling technique was used and a total of 132 students age 8-12
      years old were included. The study took places in Public Primary School 060925
      Amplas, Medan and 101747 Hamparan Perak, Deli Serdang throughout May-October
      2016. Fisher Exact test was used to analyse the correlation between STH infection
      and SI level. RESULTS: The prevalence of STH infection was 7.6%, and low SI was
      11.4%. CONCLUSION: There was no significant correlation between STH infection and
      SI level (P = 0.317). The prevalence of low SI level was not significantly
      dependent on STH infection (RP = 1.877, 95% CI = 0.481-7.181).

PMID- 28507614
TI  - Functional Pattern of Increasing Concentrations of Brain-Derived Neurotrophic
      Factor in Spiral Ganglion: Implications for Research on Cochlear Implants.
AB  - BACKGROUND: As previously various studies have suggested application of brain
      derived neurotrophic factor (BDNF) may be considered as a promising future
      therapy for hearing deficits, in particular for the improvement of cochlear
      neurone loss during cochlear implantation. AIM: The present study's aim was to
      establish the upper threshold of the concentration of BDNF in Naval Medical
      Research Institute (NMRI) mice spiral ganglion outgrowth. METHODS: Spiral
      ganglion explants were prepared from post-natal day 4 (p4) (NMRI) mice of both
      sexes under the approval and guidelines of the regional council of Hearing
      Research Institute Tubingen. RESULTS: Spiral ganglion explants were cultured at
      postnatal days 4 in the presence of different concentrations of BDNF as described
      under methods. We chose an age of postnatal day (P4) and concentrations of BDNF
      0; 6; 12.5; 25 and 50 ng/ml. Averaged neurite outgrowth is measured in 4
      different cultures that were treated with different concentrations. Results show
      that with increasing concentrations of BDNF, the neurite density increases.
      CONCLUSION: The present finding show evidence that BDNF has a clear incremental
      effect on the number of neurites of spiral ganglia in the prehearing organ, but
      less on the neurite length. The upper threshold of exogenous BNDF concentration
      on spiral ganglion explant is 25 ng/ml. This means that concentration beyond this
      level has no further incremental impact. Therefore our suggestion for hydrogel
      concentration in NMRA mice in future research should be 25 ng/ml.

PMID- 28507615
TI  - No Association between 25 (OH) Vitamin D Level And Hypothyroidism among Females.
AB  - AIM: The aim was to investigate serum vitamin D (25-OH) level among females with
      hypothyroidism. MATERIALS AND METHODS: A case-control study (58 in each arm) was
      conducted in Arar Central Hospital, Kingdom Saudi Arabia. The cases were females
      with hypothyroidism, and healthy females were controls. TSH, thyroid hormones:
      Free T3 (FT3) and Free T4 (FT4) and haemoglobin levels were measured in all
      participants. Serum vitamin D (25-OH) level was measured using the
      spectrophotometry. RESULTS: While there was no significant difference in the age
      and haemoglobin level, body mass index (BMI) was significantly higher in the
      cases. Compared with the controls, cases had significantly higher TSH, had
      significantly lower T4, and there was no significant difference in FT3 and 25
      (OH) vitamin D, [16.1 (8.8-26.7) vs. 14.0 (9.5-20.3 ng/ml; P = 0.577]. Linear
      regression showed no association between, age, BMI, haemoglobin, TSH, FT3, FT4
      and the log of 25 (OH) vitamin D levels. CONCLUSION: There was no significant
      difference in vitamin D level among females with hypothyroidism and healthy
      controls.

PMID- 28507616
TI  - Leptin and Lipid Profile in Overweight Patient with Type 1 Diabetes.
AB  - AIM: To evaluate leptin and lipid profile in overweight patients with type 1
      diabetes. PATIENTS AND METHODS: The study included 50 overweight patients with
      type 1 diabetes and 50 age and sex matched healthy controls. Blood samples were
      taken for evaluation of glycosylated haemoglobin, lipid profile and leptin. Also,
      urine samples were taken for evaluation of albumin/creatinine ratio. RESULTS:
      Leptin level was significantly lower in overweight with type 1 diabetes and
      showed a significant positive correlation with hip circumference and body mass
      index and negative correlation with glycosylated haemoglobin (HbA1c). Leptin
      level was significantly lower in overweight diabetic patients with HbA1c > 7.5 %.
      The best cut-off point between overweight diabetic group and control group
      regarding leptin levels was found at 16.9 (ng/ml) with a sensitivity of 68% and
      specificity of 56%, area under the curve 0.623. CONCLUSION: Leptin levels were
      found to be low in overweight patients with type 1 diabetes and showed
      correlation with the body mass index and hip circumference. LDL was significantly
      higher while HDL was significantly lower in the diabetic, overweight group
      indicating increased risk of cardiovascular disease. Leptin level in overweight
      diabetic patients might be related to the metabolic control.

PMID- 28507617
TI  - Serum VEGF Levels in Helicobacter pylori Infection and Correlation with
      Helicobacter pylori cagA and vacA Genes.
AB  - BACKGROUND: Helicobacter pylori vacA and cagA genes are associated with higher
      virulence. Vascular Endothelial Growth Factor (VEGF) is one important marker for
      neo-angiogenesis. AIM: The purpose of this study was to investigate the
      relationship between VEGF serum levels with cagA and vacA genes in H. pylori
      infection. METHODS: A cross-sectional study was done on eighty patients that
      consecutive admitted to endoscopy unit. The diagnosis of H. pylori infection was
      based on rapid urease test. Serum samples were obtained to determine circulating
      VEGF level. Polymerase chain reaction was done to examine H. pylori vacA and cagA
      genes. Data analysis were carried-out using SPSS version 22. RESULTS: A total of
      80 patients were examined. There were 45 (56.3%) patients infected with
      Helicobacter pylori. There were 33 (73.3%) patients with H. pylori cagA positive.
      Serum VEGF levels in patients with the H. pylori positive were significantly
      higher compared to the patients that have no H. pylori. Serum levels of VEGF were
      significantly higher in cagA positive than negative. CONCLUSION: Serum VEGF level
      is correlated with H. pylori infection and its virulence status. The more
      virulence of H. pylori, cagA gene, the higher serum VEGF levels were found.

PMID- 28507618
TI  - Correlation between Soil Transmitted Helminth Infection and Eosinophil Levels
      among Primary School Children in Medan.
AB  - BACKGROUND: Soil Transmitted Helminth infection is one of most prevalent health
      problems worldwide, especially in environments with poor sanitation. Based on
      World Health Organisation (WHO) data, more than 2 billion people, or 24% of the
      world's population, are infected with intestinal parasite. The highest prevalence
      is located in areas of poor sanitation and unsafe water supplies. In Indonesia,
      the prevalence of parasite infections is 15% of the entire population. AIM: The
      purpose of this study was to determine the relationship between Soil Transmitted
      Helminth infection on levels of eosinophils among primary school children. In
      addition, this study also aimed to determine the prevalence of different types of
      worm infections and the levels of eosinophils in children infected with worms.
      MATERIAL AND METHODS: This study was analytic observational using a cross
      sectional method. The sampling technique was consecutive and in total 132 samples
      was obtained. The study involved primary school children in Amplas Medan and
      Hamparan Perak, Deli Serdang through May to October 2016. Univariate analysis was
      performed to determine STH infection prevalence and bivariate analysis was used
      to find the correlation between STH infection and eosinophil levels through a Chi
      square (chi2) test. RESULTS: The results showed that the prevalence of Soil
      Transmitted Helminth was 7.6%. The most common types of STH infection were 3.8%
      with Trichuris trichiura and 3% with Ascaris lumbricoides. A significant
      correlation was found between Parasite infection and eosinophil levels
      (Contingency Coefficient (C) = 0.2, chi2 = 5.3, p = 0.021) and the risk of STH
      infection that caused eosinophilia or increased eosinophil levels in the children
      with a Prevalence Ratio (PR) of 1.56 (Confidence Interval (CI) 95%: 1.10-2.22).
      CONCLUSION: It is recommended that schools at similar risk improve and maintain
      hygiene and healthy behaviour in the school environment and that parents and
      teachers pay greater attention to the cleanliness of their children.

PMID- 28507620
TI  - Expression of E-Cadherin/Beta-Catenin in Epithelial Carcinomas of the Thyroid
      Gland.
AB  - BACKGROUND: The aberrant activation of Wnt signalling pathway may be a common
      denominator for the development of thyroid tumorigenesis. It was announced that
      the loss of E-cadherin rather than beta-catenin mutation represents a crucial
      event in determining the degree of differentiation of thyroid carcinomas. AIM:
      The aim of the study was to evaluate the expression of E-cadherin and beta
      catenin in the thyroid cancer tissue and to correlate these data with some
      histological and clinical parameters of the tumours. MATERIAL AND METHODS: We
      investigated 112 patients, having thyroid tumours - papillary, follicular,
      anaplastic and oncocytic carcinomas immunohistochemically with antibodies against
      E-cadherin and beta-catenin. Survival analyses were done. RESULTS: E-cadherin
      expression was focally retained in the tumour cell membranes and the tumour cell
      cytoplasm of the papillary, follicular and oncocytic thyroid cancers, weather in
      anaplastic cancers it was almost lost (p = 0.0042, and p = 0.019, respectively,
      Fisher's Exact Test). The expression of beta-catenin in tumour cytoplasm and
      membrane in papillary cancers was higher as compared to that in the other tumours
      (p = 0.111, and p = 0.0104, respectively). CONCLUSION: Not surprisingly, the
      presence of aberrant expression of E-cadherin and beta-catenin in thyroid cancer
      has been associated with better patients' prognosis and better differentiated
      tumour histology.

PMID- 28507619
TI  - Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in
      Egyptian Patients.
AB  - AIM: Prostate cancer (PCa) is the second most common cancers in men worldwide.
      Its incidence can be influenced by several risk factors including genetic
      susceptibility. Therefore the search for the expression of a certain gene (ERG)
      and its rearrangement could give us clues for proper identification of PCa. And
      the study of ERG expression and its comparison to FISH in Egyptian patients can
      show whether ERG immunophenotype could be used instead of FISH, as it is cheaper.
      MATERIALS AND METHODS: This study was performed on 85 cases of PCa, showing 30
      cases with HGPIN and 30 cases of prostatic hyperplasia. All were
      immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was
      used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to
      detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC
      TMRPSS2-ERG). RESULTS: ERG expression was found in 26% of PCa cases and 20% of
      HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases
      showing ERG immunoexpression). CONCLUSION: Our findings emphasise that only
      malignant and pre-malignant cells and not benign cells from the prostate stain
      positive. ERG expression may offer a simpler, accurate and less costly
      alternative for evaluation of ERG fusion status in PCa.

PMID- 28507621
TI  - Expression of FGFR3 Protein and Gene Amplification in Urinary Bladder Lesions in
      Relation to Schistosomiasis.
AB  - BACKGROUND: Bladder cancer represents the fifth most common malignancy worldwide
      and a major cause of cancer-related morbidity and death. Incidence and mortality
      rates have remained relatively constant over the past four decades. Urothelial
      bladder cancers have identified multiple risk factors. AIM: We aimed at
      evaluating the expression of the FGFR3 protein and gene amplification in the
      urothelial cells of neoplastic and non-neoplastic urothelial lesions of the
      urinary bladder, and correlation with tumour grade, stage and associated
      bilharziasis. MATERIAL AND METHODS: One hundred and five different urinary
      bladder lesions were studied, including 15 cystitis cases (9 bilharzial and 6 non
      bilharzial cystitides), 75 urothelial carcinoma cases (18 bilharzial associated
      and 57 non-bilharzial associated) and 15 squamous cell carcinoma associated with
      bilharziasis, beside 5 control cases. Data concerning age, sex, tumour grade,
      stage, and associated bilharziasis were obtained. Each case was studied for FGFR3
      expression, and FISH technique was applied on forty malignant cases that show
      high protein expression. RESULTS: The highest incidence of cystitis was in the
      fourth decade while of bladder cancer was in the seventh decade. Tumour grade was
      correlated significantly with tumour stage. FGFR3 correlates significantly with
      tumour grade, stage and with a bilharzial infestation. FGFR3 gene amplification
      was reported mainly in low grade and NNMBIC tumours. CONCLUSIONS: FGFR3
      overexpression in malignant cases was significantly higher than in chronic
      cystitis. FGFR3 gene amplification was reported mainly in low grade and NNMBIC
      tumours. FGFR3 may be further studied as a subject for target therapy of bladder
      cancer.

PMID- 28507622
TI  - Prognostic Value of Vascular Endothelial Growth Factor A in the Prediction of the
      Tumor Aggressiveness in Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most predominant renal
      tumour with unpredictable tumour behaviour. The aim of the study is to
      investigate the prognostic value of vascular endothelial growth factor A (VEGF-A)
      expression in CCRCC and to correlate it with other histological parameters as
      well as with patient's survival. MATERIAL AND METHODS: Tumour blocks were taken
      from 40 patients with histopathology diagnosis of CCRCC and tissue block from 20
      normal kidneys as a control group were examined using the immuno-histochemical
      staining for VEGF-A. RESULTS: The VEGF A expression in CCRCC was significantly
      higher than in the normal kidney tissues (U' = 720, P < 0.0001). VEGF A
      expression values in CCRCC were positively correlated with Disease Free Survival
      (r = 0.335, P = 0.034) and the tumor necrosis degree (r = 0.181, P = 0.262). VEGF
      A expression values in CCRCC did not correlate with CD 31 expression (r = -0.09,
      P = 0.549), and Progression Free Survival (r = -0.07, P = 0.838). VEGF A
      expression values in CCRCC were negatively correlated with the tumor nuclear
      grade (r = -0.161, P = 0.318); the pathological tumor stage (r = -0.371, P =
      0.018); the tumor size (r = -0.361, P = 0.022); the degree of tumor hemorrhage (r
      = -0.235, P = 0.143); and Cancer Specific Survival (r = -0.207, P = 0.713).
      CONCLUSIONS: VEGF-A expression can be used to stratify advanced and metastatic
      CCRCC patients into low-benefit and high-benefit groups. Based on this study
      outcome it would be useful to perform IHC staining for VEGF-A expression in all
      patients with advanced and metastatic CCRCC.

PMID- 28507623
TI  - Association between ABO and Rh Blood Groups and Risk of Preeclampsia: A Case
      Control Study from Iran.
AB  - AIM: Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and
      mortality. There is a genetic component in the development of PE with estimated
      heritability around 0.47. Several studies have investigated the association
      between maternal ABO blood groups (OMIM 110300) and risk of PE, with
      contradictory results have emerged. Considering that there is no study in this
      filed from Iranian population, the present case-control study was carried out at
      Shiraz (south-west Iran). MATERIAL AND METHODS: In this study 331 women; 121
      pregnant with PE and 210 normotensive pregnant women were included. Using blood
      group O (for ABO blood groups) or Rh+ (for Rh blood groups) as a reference, odds
      ratios (ORs) and its 95% confidence intervals (95% CI) of PE risk were estimated
      from logistic regression analysis. RESULTS: Although the A (OR = 0.67, 95% CI =
      0.39-1.17, P = 0.165), B (OR = 0.86, 95% CI = 0.48-1.53, P = 0.615) and AB (OR =
      1.14, 95% CI = 0.37-3.45, P = 0.812) phenotypes showed lower risks compared with
      the O blood group, statistical analysis indicated that there was no significant
      association between ABO phenotypes and risk of PE. The frequency of Rh- phenotype
      was higher among PE patients compared with the control group. However, the
      association was not significant (OR = 1.79, 95% CI = 0.69-4.65, P = 0.229).
      Adjusted ORs for age of participants and parity did not change the above
      mentioned associations. CONCLUSION: Our present findings indicate that there is
      no association between ABO and Rh blood groups and risk of PE in Iranian
      population.

PMID- 28507624
TI  - The Prevalence and Risk Factors of Osteoporosis among a Saudi Female Diabetic
      Population.
AB  - AIM: This study aimed to assess the prevalence and determinants of osteoporosis
      [lumbar spine (LS) and femoral neck (FN)] among patients with type 2 diabetes at
      King Salman Hospital. MATERIALS AND METHODS: One hundred seventy patients with
      type 2 diabetes were enrolled in this cross-sectional study in the period from
      the 1st of January until the 1st of July 2015. Patient selection was based on
      self-report of the previous diagnosis by a physician, being on an antidiabetic
      agent, or a fasting glucose of 126 mg/dl as per the American Diabetes Association
      criteria. A dual energy X-ray absorptiometry scan with the bone mineral density
      (BMD) categorization based on the WHO cut of levels of T-scores and determination
      of vitamin D levels were performed. A detailed questionnaire was used to collect
      demographic data. RESULTS: Out of 170 participants, 50 (29.4%) were diagnosed as
      having osteoporosis, while 68 (40%) were diagnosed with osteopenia. Age was
      determined as a risk factor for a decreased BMD in patients with osteopenia (odds
      ratio (OR) = 1.1, 95% confidence interval (CI) = (1.0-1.1), p = 0.039) and
      osteoporosis (OR = 1.1, CI = 1.0-1.2, p < 0.001). Similarly, oral hypoglycemic
      agents (OHA) increased the risk of decreased BMD in osteopenia (OR = 2.6; CI =
      1.0-6.7; p = 0.023) as well as osteoporosis, (OR = 3.8; CI = 1.3-10.9; p =
      0.013), while vitamin D deficiency increased the risk of osteopenia OR = 3.0; CI
      = 1.2-7.2; p = 0.012). Increased BMI decreased the risk of both osteopenia and
      osteoporosis (OR = 0.9; CI = 0.9-0.99; p = 0.031 vs. OR = 0.9; CI = 0.80-0.95; p
      = 0.003). CONCLUSION: Advanced age, OHA and vitamin D deficiency are determinants
      of decreased BMD in Saudi women with type 2 diabetes, while an increased BMI
      protects against low BMD.

PMID- 28507625
TI  - Surveillance of the Most Prevalent Medical Diseases among Pediatric Age Groups
      and Evaluation of the Control Measures Used At Tabuk Hospitals, Saudi Arabia.
AB  - BACKGROUND: During the last decades, medical recordings has increased
      dramatically leading to more awareness of the diseases commonly affecting
      paediatric age groups opening a wide entrance to the prevention of possible
      complications and decrease its incidence. AIM: This article aims to assess the
      prevalence of the commonly encountered paediatric medical diseases by affected
      system among admitted paediatric patients of different age groups in Tabuk and to
      identify their burden. METHODS: This is a retrospective research studying disease
      pattern according to age, gender, nationality, admission status and length of
      stay. RESULTS: Admissions due to respiratory system disorders were the most
      common among children under the age of six years (39.7%). Acute gastroenteritis
      was the most common disease leading to hospitalisation of children below the age
      of three years and cast a financial burden heavily on family and society.
      CONCLUSIONS: Respiratory diseases and acute gastroenteritis constitute a
      significant burden of childhood illnesses in Tabuk City. Efforts are required to
      reduce the impact to achieve the Saudi ministry of health (SMOH) Goal. Even
      though Rota vaccine is added to the national Saudi program of vaccination
      schedule, other causes should be looked for, and preventive measures are
      important as a part of public education.

PMID- 28507626
TI  - Follow Up of Value of the Intrarenal Resistivity Indices and Different Renal
      Biomarkers for Early Identification of Diabetic Nephropathy in Type 1 Diabetic
      Patients.
AB  - AIM: To evaluate intrarenal resistivity index (RI) and different biomarkers of
      diabetic nephropathy (DN) with clinical signs of DN and its progression over time
      as early detection of DN. PATIENTS AND METHODS: This longitudinal study included
      48 type 1 diabetic patients who were studied at baseline and after three years. A
      blood sample was taken for assessment of glycosylated haemoglobin (HbA1), lipid
      profile and a urine sample was taken for assessment of albumin/creatinine ratio,
      Neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding
      protein (L-FABP) and kidney injury molecule-1 (Kim-1) at baseline and after three
      years. Forty diabetic patients did renal Doppler at baseline & after three years.
      RESULTS: HbA1, waist/hip ratio, albumin/creatinine ratio, lipid profile, NGAL,
      KIM-1, L-FABP and resistivity index (RI) were significantly increased in follow
      up. Twenty patients (41.7%) showed progression to albuminuria. RI showed a
      significant increase in follow-up study. ROC curve showed that RI and NGAL had
      the highest sensitivity (100%), followed by L-FABP (90%) and lastly KIM-1 (63.6%)
      in the prediction of DN. CONCLUSION: High RI, NGAL, KIM-1 & L-FABP can be
      considered as early markers of diabetic nephropathy in type 1 diabetics and are
      associated with its progression over time, independent of albuminuria.

PMID- 28507627
TI  - Prenatally Diagnosis and Outcome of Fetuses with Cardiac Rhabdomyoma - Single
      Centre Experience.
AB  - BACKGROUND: Cardiac rhabdomyoma (CRs) are the most common primary tumour of the
      heart in infants and children. Usually are multiple and, basing on the location
      can cause a haemodynamic disturbance, dysrhythmias or heart failure during the
      fetal and early postnatal period. CRs have a natural history of spontaneous
      regression and are closely associated with tuberous sclerosis complex (TSC). It
      has an association with tuberous sclerosis (TS), and in those, the tumour may
      regress and disappear completely, or remain consistent in size. AIM: We aimed to
      evaluate the prenatal diagnosis, clinical presentation and outcome of CRs and
      their association with TSC in a single centre. The median follow-up period was
      three years (range: 6 months - 5 years). MATERIAL AND METHODS: We reviewed
      medical records of all fetuses diagnosed prenatally with cardiac rhabdomyoma
      covering the period January 2010 to December 2016 which had undergone detailed
      ultrasound evaluation at a single centre with limited technical resources.
      RESULTS: Twelve fetuses were included in the study; mostly had multiple tumours
      and a total of 53 tumours were identified in all patients - the maximum was one
      fetus with16 tumours. All patients were diagnosed prenatally by fetal
      echocardiography. In two patient's haemodynamic disturbances during the fetal
      period was noted and pregnancies have been terminated. After long consultation
      termination of pregnancy was chosen by the parents in totally 8 cases. In four
      continuing pregnancies during the first year of live tumours regressed. TSC was
      diagnosed in all patients during the follow-up. CONCLUSIONS: Cardiac rhabdomyoma
      are benign from the cardiovascular standpoint in most affected fetuses. An early
      prenatal diagnosis may help for an adequate planning of perinatal monitoring and
      treatment with the involvement of a multidisciplinary team. Large tumour size,
      the number of tumours and localisation may cause hydrops, and they are
      significantly associated with poor neonatal outcome.

PMID- 28507628
TI  - Does Vitamin D Deficiency Effect Heart Rate Variability in Low Cardiovascular
      Risk Population?
AB  - AIM: This study aimed to evaluate the cardiac autonomic dysfunction and the
      cardiac arrhythmia risk using heart rate variability parameters in subjects with
      vitamin D deficiency and low cardiovascular risk. MATERIAL AND METHODS: One
      hundred five consecutive individuals, 54 patients with low vitamin D status and
      51 healthy controls were enrolled in this study. The overall cardiac autonomic
      tone was quantified by using various heart rate variability parameters included
      mean RR interval, mean Heart Rate, mean of standard deviations of intervals for
      24 hours (SDNN), standard deviation of averages of intervals (SDANN), mean of
      standard deviation of intervals for 5 minutes (SDNNI), root mean square of
      difference of successive intervals (rMSSD) and the proportion of intervals
      differing more than 50 ms (pNN50) values. The 12-lead ECG was recorded from each
      participant, and QT intervals were measured. RESULTS: Baseline demographic
      profiles were similar between two groups. The heart rate variability parameters
      such as mean RR interval, mean HR, SDNN, SDANN, SDNNI, rMSSD and pNN50 (%) values
      were not significantly different in patients with low vitamin D status compared
      to control group. The electrocardiography analysis revealed only slight but
      significant prolongation of corrected QT (QTc) intervals in the control group.
      CONCLUSION: HRV variables were not significantly altered in patients with vitamin
      D deficiency in low cardiovascular risk profile group. Further studies evaluating
      these findings in other cohorts with high cardiovascular risk are required.

PMID- 28507629
TI  - Changes in Kinetic Parameters of Gait in Patients with Supratentorial Unilateral
      Stroke in Chronic Period.
AB  - AIM: The aim of the study is to evaluate the changes of the kinetic parameters of
      gait in patients with supratentorial unilateral stroke in the chronic period
      (SUSChP). MATERIAL AND METHODS: The study was conducted with 67 patients with
      SUSChP (56 patients included in the experimental group - 32 men and 24 women,
      with duration of disease 7.8 +/- 2.0 months, and 11 patients in the control group
      - 9 men and 2 women, with duration of disease 7.3 +/- 1.5 months). To evaluate
      the changes in the gait were followed cadence of 6 m and 10 m and the speed of
      movement which are the most informative kinetic parameters. Patients in the
      experimental group were treated with a specialised 10-day KT, which later
      continued to be performed as an adapted exercise program at home for one month.
      RESULTS: After applying specialised kinesitherapeutic methodology (SKTM), the
      highest trend towards improvement in the kinetic parameters of gait was
      established after the 1st month with a level of significance during treatment p <
      0.001. CONCLUSION: The enclosed SKTM in the experimental group continued later as
      an adapted exercise program at home, significantly improving the kinetic
      parameters of gait in patients with SUSChP, compared with the usual kinesi
      therapeutic methodology applied in the control group.

PMID- 28507630
TI  - Relationship between Gait Parameters and Postural Stability in Early and Late
      Parkinson's Disease and Visual Feedback-Based Balance Training Effects.
AB  - BACKGROUND: Gait disorders or postural instability has been done before. However,
      lack of reviews has addressed the relation between gait and postural stability in
      Parkinson's disease (PD). AIM: The aim was to evaluate the relation between gait
      parameters and postural stability in early and late stages of PD. MATERIALS AND
      METHODS: The forty-one idiopathic PD patients were divided into two groups into a
      group (A) considered as early PD and group (B) considered as late ambulant PD.
      They were evaluated for postural stability by computerised dynamic posturography
      (CDP) device and gait analysis using an 8 m-camera Vicon 612 data capturing
      system set. RESULTS: There was a statistically significant improvement of
      composite equilibrium score, the composite latency of motor response, walking
      speed and cadence after treatment as compared to before training (p < 0.05) in
      early PD. However, in the late PD, there was a non-significant change of previous
      parameters after treatment as compared to before training (p > 0.05). There was a
      significant correlation between UPDRS motor part score, walking speed and
      composite equilibrium score after training in early PD (p > 0.05). CONCLUSIONS:
      Both gait analysis and CDP are important quantitative assessment tools of gait
      and posture instability.

PMID- 28507631
TI  - Voiding Urosonography with Second-Generation Ultrasound Contrast Agent for
      Diagnosis of Vesicoureteric Reflux: First Local Pilot Study.
AB  - BACKGROUND: Vesicoureteric reflux (VUR) is an important association of paediatric
      urinary tract infection (UTI) found in 30-50% of all children presenting with
      first UTI. Contrast-enhanced voiding ultrasonography (ceVUS) has become an
      important radiation-free method for VUR detection in children. Its sensitivity in
      detecting VUR has greatly improved due to the development of the contrast
      specific ultrasound techniques and the introduction of the second-generation
      ultrasound contrast agent, superseding the diagnostic accuracy of standard
      radiological procedures. AIM: This article aimed to summarise the current
      literature and discuss the first local pilot study performed in our institution
      on detection of vesicoureteric reflux by contrast-enhanced voiding
      ultrasonography with second- generation agent (SonoVue, Bracco, Italy). MATERIAL
      AND METHODS: Retrospective review of the first 31 ceVUS (24 girls, 7 boys) was
      presented. Age range was 2 months to 18 years (mean = 6.4 +/- 4.9). RESULTS: All
      examinations were well tolerated without any adverse incident. VUR was shown in
      20 (64.5%) children in 32/62 (51.6) nephroureteral units (NUUs). In 18 NUUs, VUR
      was grade II/V, in 11 Grade III/V and in 3 grade IV/V, respectively. Urethra was
      shown in 19/31 children and in all boys, without pathological finding. In two
      girls spinning top urethra has been detected. Subsequent urodynamic studies
      revealed functional bladder problem in both. CONCLUSIONS: Contrast-enhanced
      voiding urosonography using intravesical second generation ultrasound contrast
      agent could be recommend as a valid alternative diagnostic modality for detecting
      vesicoureteral reflux and evaluation of the distal urinary tract in children,
      based on its radiation-free, highly efficacious, reliable, and safe
      characteristics.

PMID- 28507632
TI  - Visfatin versus Flow-Mediated Dilatation as a Marker of Endothelial Dysfunction
      in Pediatric Renal Transplant Recipients.
AB  - BACKGROUND: Renal transplantation (RTx) is the treatment of choice for paediatric
      end-stage renal disease (ESRD). A major cause of morbidity and mortality after
      RTx is cardiovascular disease. Independent predictors of cardiovascular events
      were shown to constitute an endothelial dysfunction (ED). This study aims to
      evaluate Visfatin serum level in comparison to brachial artery flow-mediated
      dilatation (FMD) as a marker of endothelial dysfunction in paediatric RTx
      recipients. METHODS: Visfatin serum level has been evaluated in 30 patients on
      regular hemodialysis (HD), 36 patients post-RTx and 30 controls as a measure for
      ED, and has been compared to brachial artery FMD. RESULTS: Visfatin level in
      transplant recipients was significantly lower than the hemodialysis group as well
      as FMD was better in transplant recipients. In spite of marked improvement of FMD
      and marked reduction of visfatin in post-RTx no direct statistical correlation
      was found between serum Visfatin level and flow-mediated dilatation. CONCLUSION:
      Pediatric RTx recipients show lower serum Visfatin level and better FMD than
      those on regular hemodialysis, reflecting less endothelial dysfunction (ED) and
      less cardiovascular risk. FMD in kidney transplant recipients tends to be less
      than normal subjects while visfatin level of the same group is similar to
      controls. Pediatric RTx appears to have a positive impact on the growth
      development of children with ESRD.

PMID- 28507633
TI  - Deep Vein Thrombosis in Upper Limb in a Weightlifter.
AB  - AIM: We report an unusual case of a male weightlifter with upper extremity venous
      thrombosis. CASE PRESENTATION: Thrombosis affecting subclavian-axillo-humeral
      venous trunk produced by the compression of these veins by the trained muscles of
      the shoulder girdle (Paget-Schroetter syndrome) has been reported. During the
      study, a renal carcinoma was detected. Renal carcinoma has rarely been associated
      with thrombosis in the upper extremities. CONCLUSION: This case shows the
      importance of performing a complete study to rule out malignancies in patients
      with unusual venous thromboembolism.

PMID- 28507634
TI  - Multi-System Complications after Intravenous Cocaine Abuse.
AB  - BACKGROUND: Use and abuse of cocaine are associated with numerous adverse
      effects, independent of the route of administration. More severe conditions of
      poisoning, however, are observed after cocaine intravenous administration. AIM:
      We present a case of severe poisoning after violent intravenous injection of
      cocaine, but with a good outcome. CASE PRESENTATION: Cocaine was intravenously
      (i.v.) administered in 16-years old female patient as a homicide attempt. Shortly
      after that, patient experienced series of generalised tonic-clonic seizures, was
      highly febrile (40 degrees C), somnolent, agitated, presenting with tachycardia,
      tachypnea and with increased blood pressure 150/90 mmHg. Neurologic status,
      lumbar puncture and computerised tomography (CT) of the brain were without
      remarks. Electroencephalogram (EEG) was characterised with signs of diffuse
      encephalopathy, and acid-base analyses resulted in metabolic acidosis. Urine
      screening revealed the presence of cocaine and benzodiazepines. The patient
      presented with signs of the hepatic lesion, acute renal insufficiency (ARI), and
      increased D-dimers resulting from activated fibrinolysis. The patient was
      discharged in stable general condition after being hospitalised for 23 days.
      CONCLUSION: Intravenous abuse of cocaine results in overdose and serous multi
      system complications requiring multidisciplinary diagnostic and intensive
      therapeutic approach.

PMID- 28507636
TI  - Influence of Number of Implants and Attachment Type on Stress Distribution in
      Mandibular Implant-Retained Overdentures: Finite Element Analysis.
AB  - AIM: This study aimed to compare the stresses generated by using two or four root
      form dental implants supporting mandibular overdentures that were retained with
      ball and locator attachments. METHODS: Under ANSYS environment, four 3D finite
      element models were prepared. These models simulated complete overdentures
      supported by two or four implants with either ball or locator attachments as a
      connection mechanism. The models' components were created by CAD/CAM package then
      were imported to ANSYS. Load of 100 N was applied at the right premolar/molar
      region vertically and at an oblique angle of 110 degrees  from lingual direction.
      RESULTS: Within the conditions of this research, in all cases, it was found that
      cortical and cancellous bone regions were the least to be stressed. Also, the
      ball attachment produced higher stresses. CONCLUSION: Caps deformation and
      stresses are negligible in cases of using locator attachment in comparison to
      ball attachments. This may indicate longer lifetime and less repair/maintenance
      operations in implant overdentures retained by locator attachments. Although the
      study revealed that bone was insensitive to a number of implants or attachment
      type, it may be recommended to use two implants in the canine region than using
      four, where the locator attachments were found to be better.

PMID- 28507635
TI  - Salivary Immunoglobulin Gene Expression in Patients with Caries.
AB  - BACKGROUND: Immunoglobulins mediate the host's humoral immune response are
      expressed in saliva. AIM: To quantify the FcalphaR, FcgammaRIIB, and FcalphaMUR
      gene expression in the saliva of Mexican patients with caries in mixed and
      permanent dentition. SUBJECTS AND METHODS: This was a comparative cross-sectional
      study. mRNA was isolated from 200 MUL of saliva following the RNA III Tissue
      Fresh-frozen protocol of the MagNA Pure LC Instrument 2.0 (Roche Diagnostics
      GmbH, Nederland BV) and the FcalphaR, FcalphaMUR and FcgammaRIIB were quantified
      through TaqMan Assays. RESULTS: One hundred individuals, 50 with mixed dentition
      and 50 with permanent dentition, were included in the study. Statistically, it
      was found a significant difference (p = 0.025) in the IgG (FcgammaRIIB)
      expression between the studied groups. CONCLUSION: Although we confirmed the
      existence of FcalphaR, FcgammaRIIB and FcalphaMUR gene expression in saliva, only
      a significant difference in the expression of FcgammaRIIB between the mixed
      dentition and permanent dentition was found.

PMID- 28507637
TI  - Factors Influencing Antenatal Haematinics Prescription Behaviour of Physicians in
      Calabar, Nigeria.
AB  - BACKGROUND: Routine iron and folic acid supplementation in pregnancy have been
      proved to be effective in reducing the prevalence and morbidities of anaemia.
      However, there is limited data regarding the prescription habits of physician
      obstetric care givers. AIM: This study set to investigate the attitudes and
      factors which influence the practice among physicians in University of Calabar
      Teaching Hospital (UCTH). MATERIAL AND METHODS: A questionnaire based cross
      sectional survey was conducted among randomly recruited physician offering
      antenatal services between August and September 2015. Systemic sampling was used
      to select 70 doctors in the departmental duty roster. Data were presented in
      percentages and proportion. Chi-square test was used to test the association
      between variables. Statistical significance was set at p < 0.05. RESULTS: The
      response rate was 100%. The mean age of the respondents was 30.26 +/- 6.67 years.
      All the respondents routinely prescribed haematinics to pregnant women but 34.3%
      of them did not prescribe to apparently healthy clients in their first trimester.
      Only 30% and 11.4% of them prescribed it in the postnatal and preconception
      periods respectively. Brands that contained iron, folate and vitamins as a single
      capsule were mostly favoured, and information about brands of drugs was mostly
      provided by the pharmaceutical sales representatives. Younger doctors were more
      likely to offer haematinics with nutritional counselling compared to older
      respondents. However, there was no significant relationship between haematinics
      prescription and sex (p = 0.3560), Age (p = 0.839), current professional status
      (p = 0.783), and client complaint of side effect of medication (p = 0.23). Oral
      medication was mostly utilised. CONCLUSION: Effort to effectively control anaemia
      in pregnancy should involve re-orientation of physician obstetric care providers
      especially about prenatal and postnatal medication and counselling.

PMID- 28507638
TI  - Antibiotic Utilization in Pediatric Hospitalized Patients - A Single Center
      Study.
AB  - BACKGROUND: Antibiotics are among the most commonly prescribed drugs in
      paediatrics. In most cases, antibiotics are started on an empirical basis,
      without proof of a bacterial infection, either before the start of therapy or
      afterwards. AIM: The main objective of this study was to analyse the consumption
      of antibiotics in hospitalised paediatric patients. MATERIAL AND METHODS: This
      retrospective study investigated the consumption of antimicrobials in defined
      daily doses (DDDs according to the Anatomical Therapeutical Chemical/DDD index)
      in Pulmonology, Gastroenterology and Nephrology Departments at Pediatric Clinic
      of the tertiary hospital. The data on the consumption of antimicrobials were
      collected for five years by using properly designed form. The consumption was
      related to days of hospital care. RESULTS: The most utilised antibiotics group in
      all three departments Pulmonology, Gastroenterology and Nephrology Departments
      were penicillins. Cephalosporins were mostly used in Pulmonology department.
      Metronidazole and Chloramphenicol were used in minimal quantities in all three
      departments. CONCLUSION: This study demonstrates that surveillance programs on
      antibiotic resistance should be established and accompanied by analyses of drug
      utilisation data which can aid in the creation of valid cross-national studies on
      antibiotic usage and resistance, to motivate improvements in prescribing and
      guideline-directed antibiotic prescribing.

PMID- 28507639
TI  - Comparative Assessment of Women's Reproductive Health in the Areas Bordering With
      the Aral Sea Region.
AB  - AIM: We examined 435 women of Aktobe region and 328 women of South Kazakhstan
      region, living in areas bordering the Aral Sea region during the study and
      comparative assessment of the impact of climatic and anthropogenic factors of
      Aral region on the reproductive health of the female population. MATERIAL AND
      METHODS: The survey based on the comprehensive clinical-functional and laboratory
      studies accounting the regional and environmental ecological factors. Survey
      subject was the area of 2 settlements of Aktobe region and 1 settlement of South
      Kazakhstan region. RESULTS: In all three areas it was revealed that the examined
      women had the later menarche. There is a trend towards younger age for menopause.
      The women of South Kazakhstan region often suffer from the pelvic inflammatory
      disease. CONCLUSION: Perinatal losses, the case of spontaneous interruption and
      stagnant pregnancy in history, which can be repeated, one in three women has in
      the zone of ecological disaster.

PMID- 28507640
TI  - Histopathological Features of Methotrexate Induced Pulmonary Lesions in
      Rheumatoid Arthritis Patients: A Systematic Review of Case Reports.
AB  - BACKGROUND: Methotrexate (MTX) is the most commonly used disease-modifying drug
      in the treatment of rheumatoid arthritis (RA); however, it causes many side
      effects, including pulmonary lesions. In this review, we characterised the
      histopathological features of MTX-induced pulmonary lesions in RA patients. AIM:
      We carried out an electronic search of the relevant literature published during
      the period from 1990 to 2016. We included only the cases with definitive histo
      pathological findings caused by MTX therapy. MATERIAL AND METHODS: The total
      number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87
      years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia
      (55%), Europe (41%), and America (4%). The major complications of methotrexate
      therapy were lymphoproliferative disorders (42%) followed by interstitial
      fibrosis (33), and infections (25%). The incidence of these complications
      significantly increases with the duration of MTX treatment (p = 0.044). Among the
      infections, the most common causative organism was pneumocystis jiroveci. The
      majority of patients who developed infections following methotrexate therapy were
      from Europe whereas the majority of those who developed lymphoproliferative
      disorders were from Asia (p = 0.003). CONCLUSION: In conclusion, methotrexate
      therapy in rheumatoid arthritis patients causes different types pulmonary
      complications.

PMID- 28507642
TI  - Diagnostic Imaging of Pregnant Women - The Role of Magnetic Resonance Imaging.
AB  - BACKGROUND: Presentation of magnetic resonance imaging (MRI) findings in pregnant
      women in the Department of Diagnostic Imaging, Institute of Mother and Child,
      Warsaw, Poland. MATERIAL/METHODS: Forty-three symptomatic pregnant women
      underwent MRI between 9 and 33 weeks of gestation (mean of 23 weeks). Moreover,
      we included 2 pregnant women who underwent fetal MRI and had incidental
      abnormalities. RESULTS: In 9 cases, we excluded the suspected brain
      abnormalities. In 4 cases, we found unremarkable changes in the brain without
      clinical significance. One patient was diagnosed with multiple sclerosis, one
      with cortical dysplasia, one with pineal hemorrhage and one with a brain tumor.
      On abdominal MRI, 2 patients had normal findings, one patient had colon cancer
      with a hepatic metastasis, one patient had a hepatic angioma, one patient had an
      extraadrenal pheochromocytoma, one patient had an abscess in the iliopsoas
      muscle, 9 patients had myomas, two patients had ovarian simple cysts, two
      endometrial cysts, three dermoid cysts, one patient had sacrococcygeal teratoma,
      one patient had a cystadenofibroma (partial borderline tumor), one patient had an
      androgenic ovarian tumor and two patients had hyperreactio luteinalis. One
      patient was diagnosed with transient osteoporosis of the hip and one with a
      stress fracture of the sacral bone. CONCLUSIONS: Magnetic resonance imaging is
      the best imaging modality for pregnant women. Although ultrasonography is the
      method of choice, doubtful cases as well as structures that cannot be examined
      with ultrasonography can be non-invasively evaluated with MRI.

PMID- 28507641
TI  - A case report of Muir-Torre syndrome in a woman with breast cancer and MSI-Low
      skin squamous cell carcinoma.
AB  - BACKGROUND: The tumor spectrum in the Lynch syndrome is well defined, comprising
      an increased risk of developing colonic and extracolonic malignancies. Muir-Torre
      syndrome is a variant with a higher risk of skin disease. Patients have been
      described carrying mutations in the mismatch repair genes and presenting tumors
      with unusual histology or affected organ not part of the Lynch syndrome spectrum.
      Hence, the real link between Lynch syndrome, or Muir-Torre syndrome, and these
      tumors remains difficult to assess. CASE PRESENTATION: We present the case of a
      45-year-old-woman, diagnosed with breast cancer at 39 years of age and skin
      squamous cell carcinoma (SCC) at 41 years of age, without personal history of
      colorectal cancer. The microsatellite instability analysis performed on the skin
      SCC showed a low-level of microsatellite instability (MSI-Low). The
      immunohistochemical expression analysis of the four DNA mismatch repair proteins
      MLH1, MSH2, MSH6 and PMS2 showed a partial loss of the expression of MSH2 and
      MSH6 proteins. Germline deletion was found in MSH2 gene (c.1277-? _1661 + ?del),
      exon 8 to 10. Then, at 45 years of age, she presented hyperplastic polyps of the
      colon and a sebaceous adenoma. CONCLUSION: Squamous cell carcinomas have been
      described in Lynch syndrome and Muir-Torre syndrome in two studies and two case
      reports. This new case further supports a possible relationship between Lynch
      syndrome and squamous cell carcinoma.

PMID- 28507643
TI  - Imaging of Complications After Limb Prostheses Implantation in Children with Bone
      Tumors.
AB  - BACKGROUND: Tumors of the developmental age are an important problem in clinical
      practice. Primary bone tumors constitute 1-1.5% of all tumors, and 7% of all
      tumors diagnosed in the developmental age. The aim of the study was to assess the
      capabilities of imaging methods in diagnosing complications of limb
      endoprostheses in children with osteoarticular tumors. MATERIAL/METHODS: We
      included 155 patients with limb endoprostheses, aged 7-26 years. There were 113
      patients with knee prostheses, 1 patient with bilateral knee prostheses, 16
      patients with shoulder prostheses, 14 patients with hip prostheses, 11 patients
      with hip and knee prostheses, and 1 patient with a femoral prosthesis. All
      patients underwent plain radiography and an ultrasound study. RESULTS:
      Complications were found in 50 patients (32% of all patients). The following
      complications were seen - inflammatory changes in soft tissues and bones (12
      patients, 7.7%), stump fractures (11 patients, 7%), lack of elongation effect or
      shortening of the prosthesis (7 patients, 4.5%), prosthesis fractures (4
      patients, 2.5%), crural fractures (4 patients, 2.5%), loosening of the prosthesis
      (3 patients, 1.9%), joint dislocation (2 patients, 1.3%), stump and prosthesis
      fracture (1 patient, 0.6%) and local recurrence (6 patients, 3.9%). Prostheses
      were exchanged for the following reasons - fractures (5 patients, 3.2%),
      inflammation (2 patients with 3 exchanges, 1.9%). Local recurrence and
      inflammation were confirmed by a biopsy. CONCLUSIONS: Radiography and
      ultrasonography are of crucial importance in monitoring patients after
      implantation of limb endoprostheses. The findings did not require confirmation in
      additional studies: CT and MRI. Suspicion of local recurrence and inflammation
      required a biopsy confirmation.

PMID- 28507645
TI  - Pharmacists vs employers: A showdown over professional autonomy and patient care?

PMID- 28507646
TI  - ?

PMID- 28507644
TI  - Autoimmune Pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a rare and underdiagnosed fibrosclerosing
      inflammatory variant of chronic pancreatitis. Its true incidence and prevalence
      in the general population is still not confirmed despite advances in medicine.
      Differentiating it from pancreatic cancer is of paramount importance. In this
      imaging review, we highlight the imaging findings of this intriguing entity.

PMID- 28507647
TI  - The cost of drugs.

PMID- 28507648
TI  - Innovative pharmacy practice: Rick Siemens.

PMID- 28507649
TI  - Managing medications during Ramadan fasting.

PMID- 28507650
TI  - Part 1: Barriers to the advancement of the pharmacy profession.

PMID- 28507651
TI  - Part 2: Roles and expertise needed to move the profession forward and improve
      health outcomes.

PMID- 28507652
TI  - Practice guidelines for pharmacists: The management of osteoarthritis.

PMID- 28507653
TI  - Use of potentially inappropriate medications among ambulatory home-dwelling
      elderly patients with dementia: A review of the literature.
AB  - BACKGROUND: Older adults with dementia are at high risk for drug-related adverse
      outcomes. While much is known about potentially inappropriate medication use in
      older adults, its prevalence and characteristics among those with dementia are
      not as well elucidated. We conducted a literature review to examine the
      prevalence of potentially inappropriate medication use among home-dwelling older
      adults with dementia. Our secondary aim was to determine the most frequently
      implicated medications and factors associated with potentially inappropriate
      medication use. METHODS: MEDLINE, EMBASE, CINAHL, and International
      Pharmaceutical Abstracts were searched between 1946 and 2014 for articles that
      referenced potentially inappropriate medication use and types of dementia. One
      reviewer screened all titles and abstracts from the initial search and full-text
      articles after the initial screen for eligibility, then 2 reviewers independently
      abstracted data from included studies. RESULTS: Searches yielded 81 articles, of
      which 7 met inclusion criteria. Prevalence of potentially inappropriate
      medication use varied from 15% to 46.8%. No single drug or drug class was
      reported consistently across all studies as the most frequent potentially
      inappropriate medication, but anticholinergics and benzodiazepines, drugs that
      affect cognition, were among the most common medications or pharmacological
      classes listed. DISCUSSION: Older adults with dementia may be particularly
      vulnerable to potentially inappropriate medications because of cognitive
      impairment from their condition and the greater likelihood of experiencing
      adverse events from medications. Given this population's greater susceptibility
      to adverse events, more intense medication and patient monitoring may be
      warranted, especially among those taking anticholinergics and benzodiazepines, as
      these drugs can contribute to cognitive impairment.

PMID- 28507655
TI  - How are pharmacists in Ontario adapting to practice change? Results of a
      qualitative analysis using Kotter's change management model.
AB  - BACKGROUND: The pace of practice change in community pharmacy over the past
      decade has been significant, yet there is little evidence documenting
      implementation of change in the profession. METHODS: Kotter's change management
      model was selected as a theoretical framework for this exploratory qualitative
      study. Community pharmacists were interviewed using a semistructured protocol
      based on Kotter's model. Data were analyzed and coded using a constant
      comparative iterative method aligned with the stages of change management
      outlined by Kotter. RESULTS: Twelve community pharmacists were interviewed. Three
      key themes emerged: 1) the profession has successfully established the urgency
      to, and created a climate conducive for, change; 2) the profession has been less
      successful in engaging and enabling the profession to actually implement change;
      and 3) legislative changes (for example, expansion of pharmacists' scope of
      practice) may have occurred prematurely, prior to other earlier stages of the
      change process being consolidated. INTERPRETATION: As noted by most participants,
      allowing change is not implementing change: pharmacists reported feeling
      underprepared and lacking confidence to actually make change in their practices
      and believe that more emphasis on practical, specific implementation tactics is
      needed. CONCLUSIONS: Change management is complex and time and resource
      intensive. There is a need to provide personalized, detailed, context-specific
      implementation strategies to pharmacists to allow them to take full advantage of
      expanded scope of practice.

PMID- 28507654
TI  - Cost-effectiveness of pharmacist care for managing hypertension in Canada.
AB  - BACKGROUND: More than half of all heart disease and stroke are attributable to
      hypertension, which is associated with approximately 10% of direct medical costs
      globally. Clinical trial evidence has demonstrated that the benefits of
      pharmacist intervention, including education, consultation and/or prescribing,
      can help to reduce blood pressure; a recent Canadian trial found an 18.3 mmHg
      reduction in systolic blood pressure associated with pharmacist care and
      prescribing. The objective of this study was to evaluate the economic impact of
      such an intervention in a Canadian setting. METHODS: A Markov cost-effectiveness
      model was developed to extrapolate potential differences in long-term
      cardiovascular and renal disease outcomes, using Framingham risk equations and
      other published risk equations. A range of values for systolic blood pressure
      reduction was considered (7.6-18.3 mmHg) to reflect the range of potential
      interventions and available evidence. The model incorporated health outcomes,
      costs and quality of life to estimate an overall incremental cost-effectiveness
      ratio. Costs considered included direct medical costs as well as the costs
      associated with implementing the pharmacist intervention strategy. RESULTS: For a
      systolic blood pressure reduction of 18.3 mmHg, the estimated impact is 0.21
      fewer cardiovascular events per person and, discounted at 5% per year, 0.3
      additional life-years, 0.4 additional quality-adjusted life-years and $6,364 cost
      savings over a lifetime. Thus, the intervention is economically dominant, being
      both more effective and cost-saving relative to usual care. DISCUSSION: Across a
      range of one-way and probabilistic sensitivity analyses of key parameters and
      assumptions, pharmacist intervention remained both effective and cost-saving.
      CONCLUSION: Comprehensive pharmacist care of hypertension, including patient
      education and prescribing, has the potential to offer both health benefits and
      cost savings to Canadians and, as such, has important public health implications.

PMID- 28507656
TI  - Development of a Pharmacist REferral Program in a primary cARE clinic (PREPARE):
      A prospective cross-sectional study.
AB  - BACKGROUND: Increasing demand for ambulatory health care services has led to the
      development of primary care multidisciplinary teams that include pharmacists. The
      objective of this study was to characterize referrals to a pharmacist in a
      primary care clinic (PCC) based in Chilliwack, British Columbia. METHODS: This
      prospective cross-sectional study included all patients referred to the PCC
      pharmacist over 12 months (May 2015 to April 2016). Data regarding the
      source/reason for referral, patient demographics, medical problems/medications
      and number/category of identified drug therapy concerns (DTCs) were collected.
      RESULTS: A total of 137 referrals were received. Mean age was 60 years and 59%
      were female. Twenty patients (15%) did not attend their appointment. Fifty-eight
      percent were new clinic patients identified using a Medication Risk Assessment
      Questionnaire (MRAQ), 30% were from PCC clinicians and 12% were from community
      family physicians. The most common reason for referral was for a medication
      review (82%). Median number of medical problems and medications per patient were
      7 (interquartile range [IQR] 5) and 11 (IQR 7.5), respectively. A total of 460
      DTCs were identified (median 4 per patient, IQR 3.5), of which 34% were
      medication without an indication and 28% an untreated indication. DISCUSSION AND
      CONCLUSION: The most common source of referrals to a PCC pharmacist was for
      medication reviews of new patients using an MRAQ. Most referred patients had
      multiple medical problems and polypharmacy, and few were referred for disease
      specific management. The number of DTCs per patient was variable and, despite
      polypharmacy being commonplace, almost one-third of patients had an untreated
      indication.

PMID- 28507658
TI  - Canadian Pharmacists Conference 2017 Sponsors.

PMID- 28507657
TI  - The essential role of pharmacists in the opioid crisis.

PMID- 28507660
TI  - Severe Knee Pain in a 22-year-old Woman After Trauma.

PMID- 28507659
TI  - Diagnosis of Arteriovenous Malformation in the Finger.

PMID- 28507661
TI  - Bone Marrow Aspirate Concentrate in Combination With Intravenous Iloprost
      Increases Bone Healing in Patients With Avascular Necrosis of the Femoral Head: A
      Matched Pair Analysis.
AB  - With disease progression, avascular necrosis (AVN) of the femoral head may lead
      to a collapse of the articular surface. The exact pathophysiology of AVN remains
      unclear, although several conditions are known that can result in spontaneous
      cell death, leading to a reduction of trabecular bone and the development of AVN.
      Hip AVN treatment is stage-dependent in which two main stages of the disease can
      be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV,
      crescent sign). In the pre-collapse phase, core decompression (CD), with or
      without the addition of bone marrow (e.g. bone marrow aspirate concentrate, BMAC)
      or bone graft, is a common treatment alternative. In the post-collapse phase, THA
      (total hip arthroplasty) must be performed in most of the patients. In addition
      to surgical treatment, the intravenous application of Iloprost has been shown to
      have a curative potential and analgesic effect. From October 2009 to October
      2014, 49 patients with AVN (stages I-III) were treated with core decompression at
      our institution. All patients were divided into group A (CD + BMAC) and group B
      (CD alone). Of these patients, 20 were included in a matched pair analysis. The
      patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic
      angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle
      d'Aubigne Score and the Kerboul combined necrotic angle in a-p and lateral
      radiographs were evaluated pre- and postoperatively. The primary endpoint was a
      total hip arthroplasty. In group A, two patients needed THA while in group B four
      patients were treated with THA. In group A, the Merle d'Aubigne Score improved
      from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no
      difference between the pre- (14.3) and postoperative (14.1) assessment. The mean
      of the Kerboul angle showed no difference in both groups compared pre- to
      postoperatively (group A: pre-op 212 degrees , postop 220 degrees , group B: pre
      op 213, postop 222 degrees ). Regarding radiographic evaluation, the
      interobserver variability revealed a moderate agreement between two raters
      regarding the pre-(ICC 0.594) and postoperative analysis (ICC 0.604).This study
      demonstrates that CD in combination with the application of autologous bone
      marrow aspirate concentrate into the femoral head seems to be a safe and
      efficient treatment alternative in the early stages of AVN of the femoral head
      when compared to CD alone.

PMID- 28507662
TI  - Fabrication and nanostructure control of super-hierarchical carbon materials from
      heterogeneous bottlebrushes.
AB  - Advances in the performances of many modern materials fundamentally depend upon
      the exploitation of new micro/nanostructures. Therefore, ingenious design of
      hierarchical structures through the mimicking of natural systems is of increasing
      importance. Currently, there is an urgent need for creation of multidimensional
      carbonaceous structures by integrating a customized hierarchical pore
      architecture and hybrid carbon framework. Here we report the pioneering
      fabrication of novel super-hierarchical carbons with a unique carbonaceous hybrid
      nanotube-interconnected porous network structure by utilizing well-defined carbon
      nanotube@polystyrene bottlebrushes as building blocks. Hypercrosslinking of such
      heterogeneous core-shell structured building blocks not only allows for
      constructing amorphous microporous carbon shells on the surface of graphitic
      carbon nanotube cores, but also leads to formation of covalently interconnected
      nanoscale networks. Benefiting from such a well-orchestrated structure, these
      super-hierarchical carbons exhibit good electrochemical performances. Our
      findings may open up a new avenue for fabrication of unique and unusual
      functional carbon materials which possess well-orchestrated structural hierarchy
      and thus generate valuable breakthroughs in many applications including energy,
      adsorption, separation, catalysis and medicine.

PMID- 28507663
TI  - Molecular engineering and sequential cosensitization for preventing the "trade
      off" effect with photovoltaic enhancement.
AB  - In dye-sensitized solar cells (DSSCs), it is essential to use rational molecular
      design to obtain promising photosensitizers with well-matched energy levels and
      narrow optical band gaps. However, the "trade-off" effect between the
      photocurrent and photovoltage is still a challenge. Here we report four
      benzoxidazole based D-A-pi-A metal-free organic dyes (WS-66, WS-67, WS-68 and WS
      69) with different combinations of pi-spacer units and anchoring-acceptor groups.
      Either extending the pi-spacer or enhancing the electron acceptor can efficiently
      modulate the molecular energy levels, leading to a red-shift in the absorption
      spectra. The optimal dye, WS-69, containing a cyclopentadithiophene (CPDT) spacer
      and cyanoacetic acid acceptor, shows the narrowest energy band gap, which
      displays a very high photocurrent density of 19.39 mA cm-2, but suffers from a
      relatively low photovoltage of 696 mV, along with the so-called deleterious
      "trade-off" effect. A cosensitization strategy is further adopted for enhancing
      the device performance. Optimization of the dye loading sequence is found to be
      capable of simultaneously improving the photocurrent and photovoltage, and
      distinctly preventing the "trade-off" effect. The superior cosensitized cell
      exhibits an excellent power-conversion efficiency (PCE) of 10.09% under one-sun
      irradiation, and 11.12% under 0.3 sun irradiation, which constitutes a great
      achievement in that the efficiency of a pure metal-free organic dye with iodine
      electrolyte can exceed 11% even under relatively weak light irradiation. In
      contrast with the previous cosensitization strategy which mostly focused on
      compensation of light-harvesting, we propose a novel cosensitization
      architecture, in which the large molecular-sized, high photocurrent dye WS-69
      takes charge of broadening the light-harvesting region to generate a high short
      circuit current (JSC) while the small molecular-sized, high photovoltage dye WS-5
      is responsible for retarding charge recombination to generate a high open-circuit
      voltage (VOC). In addition, adsorption amount and photo-stability studies suggest
      that the cyano group in the anchoring acceptor is important for the stability
      since it is beneficial towards decreasing the LUMO levels and enhancing the
      binding of dyes onto TiO2 nanocrystals.

PMID- 28507664
TI  - Coevolution and ratiometric behaviour in metal cation-driven dynamic covalent
      systems.
AB  - Dynamic Covalent Libraries (DCLs) have been used to demonstrate coevolution
      behaviour on a molecular level using dynamic covalent molecules such as imines
      and hydrazones. Two systems are presented: the first system is based on a
      dialdehyde and two diamines in combination with Zn(ii) and Hg(ii) to form a 2 * 2
      Constitutional Dynamic Network (CDN) of four complexes of macrocyclic bis-imines.
      Whereas the two metal ions, when reacted separately form a complex with each
      macrocycle with low selectivity, when applied together, each cation yields
      selectively a complex with one of the two macrocycles. Thus, the simultaneous
      application of both cations, where one might have expected the formation of four
      different complexes, results in the synergistic evolution (co-evolution) towards
      a simpler, more selective outcome under agonist amplification. The second system
      of 4 components, 2 amines and 2 aldehydes displays metalloselection together with
      a correlated evolution in distribution on complexation of Zn(ii) and Cu(i) with
      the dynamic ligand constituents and exhibits a dynamic ratiometry process related
      to the antagonistic behaviour of a pair of ligand constituents.

PMID- 28507665
TI  - Versatile routes for synthesis of diarylamines through acceptorless
      dehydrogenative aromatization catalysis over supported gold-palladium bimetallic
      nanoparticles.
AB  - Diarylamines are an important class of widely utilized chemicals, and development
      of diverse procedures for their synthesis is of great importance. Herein, we have
      successfully developed novel versatile catalytic procedures for the synthesis of
      diarylamines through acceptorless dehydrogenative aromatization. In the presence
      of a gold-palladium alloy nanoparticle catalyst (Au-Pd/TiO2), various
      symmetrically substituted diarylamines could be synthesized starting from
      cyclohexylamines. The observed catalysis of Au-Pd/TiO2 was heterogeneous in
      nature and Au-Pd/TiO2 could be reused several times without severe loss of
      catalytic performance. This transformation needs no oxidants and generates
      molecular hydrogen (three equivalents with respect to cyclohexylamines) and
      ammonia as the side products. These features highlight the environmentally benign
      nature of the present transformation. Furthermore, in the presence of Au-Pd/TiO2,
      various kinds of structurally diverse unsymmetrically substituted diarylamines
      could successfully be synthesized starting from various combinations of
      substrates such as (i) anilines and cyclohexanones, (ii) cyclohexylamines and
      cyclohexanones, and (iii) nitrobenzenes and cyclohexanols. The role of the
      catalyst and the reaction pathways were investigated in detail for the
      transformation of cyclohexylamines. The catalytic performance was strongly
      influenced by the nature of the catalyst. In the presence of a supported gold
      nanoparticle catalyst (Au/TiO2), the desired diarylamines were hardly produced.
      Although a supported palladium nanoparticle catalyst (Pd/TiO2) gave the desired
      diarylamines, the catalytic activity was inferior to that of Au-Pd/TiO2.
      Moreover, the activity of Au-Pd/TiO2 was superior to that of a physical mixture
      of Au/TiO2 and Pd/TiO2. The present Au-Pd/TiO2-catalyzed transformation of
      cyclohexylamines proceeds through complex pathways comprising amine
      dehydrogenation, imine disproportionation, and condensation reactions. The amine
      dehydrogenation and imine disproportionation reactions are effectively promoted
      by palladium (not by gold), and the intrinsic catalytic performance of palladium
      is significantly improved by alloying with gold. One possible explanation of the
      alloying effect is the formation of electron-poor palladium species that can
      effectively promote the beta-H elimination step in the rate-limiting amine
      dehydrogenation.

PMID- 28507666
TI  - In situ observation of reactive oxygen species forming on oxygen-evolving iridium
      surfaces.
AB  - Water splitting performed in acidic media relies on the exceptional performance
      of iridium-based materials to catalyze the oxygen evolution reaction (OER). In
      the present work, we use in situ X-ray photoemission and absorption spectroscopy
      to resolve the long-standing debate about surface species present in iridium
      based catalysts during the OER. We find that the surface of an initially metallic
      iridium model electrode converts into a mixed-valent, conductive iridium oxide
      matrix during the OER, which contains OII- and electrophilic OI- species. We
      observe a positive correlation between the OI- concentration and the evolved
      oxygen, suggesting that these electrophilic oxygen sites may be involved in
      catalyzing the OER. We can understand this observation by analogy with
      photosystem II; their electrophilicity renders the OI- species active in O-O bond
      formation, i.e. the likely potential- and rate-determining step of the OER. The
      ability of amorphous iridium oxyhydroxides to easily host such reactive,
      electrophilic species can explain their superior performance when compared to
      plain iridium metal or crystalline rutile-type IrO2.

PMID- 28507668
TI  - Triflimide-catalyzed allylsilane annulations of benzylic alcohols for the
      divergent synthesis of indanes and tetralins.
AB  - The development of a triflimide-catalyzed annulation of benzylic alcohols with
      allylsilanes for the synthesis of indane or tetralin structures is reported. In
      this fragment coupling reaction, complexity is built rapidly from readily
      available starting materials to yield diverse sets of products with up to three
      contiguous stereocenters. Indanes or tetralins can be generated from common
      precursors depending on the structure of the allylsilane reagent used. The
      concise synthesis of several lignan natural products highlights the utility of
      this newly devised methodology.

PMID- 28507667
TI  - Photoacoustic probes for real-time tracking of endogenous H2S in living mice.
AB  - H2S is a key chemical mediator that exerts a vital role in diverse physiological
      and pathological processes. However, in vivo tracking of endogenous H2S
      generation still remains difficult due to the lack of reliable analytical
      methods. Herein, we present the first example of activatable photoacoustic probes
      for real-time imaging of H2S in living mice through the full utilization of the
      superiority of photoacoustic imaging modality at fine spatial resolution during
      deep tissue penetration. The designed probe can generate high NIR absorption at
      780 nm in the presence of H2S, thus producing a strong photoacoustic signal
      output in the NIR region. Furthermore, this probe exhibits extremely fast and
      highly selective responsiveness, good water-solubility and excellent
      biocompatibility. In light of these outstanding features, this probe realizes the
      direct photoacoustic trapping of endogenous H2S generation in a HCT116 tumor
      bearing mouse model. These preliminary imaging studies show that HCT116 colon
      tumors exhibit CBS upregulation activity, resulting in an increased rate of H2S
      generation.

PMID- 28507669
TI  - Continuous variables logic via coupled automata using a DNAzyme cascade with
      feedback.
AB  - The concentration of molecules can be changed by chemical reactions and thereby
      offer a continuous readout. Yet computer architecture is cast in textbooks in
      terms of binary valued, Boolean variables. To enable reactive chemical systems to
      compute we show how, using the Cox interpretation of probability theory, one can
      transcribe the equations of chemical kinetics as a sequence of coupled logic
      gates operating on continuous variables. It is discussed how the distinct
      chemical identity of a molecule allows us to create a common language for
      chemical kinetics and Boolean logic. Specifically, the logic AND operation is
      shown to be equivalent to a bimolecular process. The logic XOR operation
      represents chemical processes that take place concurrently. The values of the
      rate constants enter the logic scheme as inputs. By designing a reaction scheme
      with a feedback we endow the logic gates with a built in memory because their
      output then depends on the input and also on the present state of the system.
      Technically such a logic machine is an automaton. We report an experimental
      realization of three such coupled automata using a DNAzyme multilayer signaling
      cascade. A simple model verifies analytically that our experimental scheme
      provides an integrator generating a power series that is third order in time. The
      model identifies two parameters that govern the kinetics and shows how the
      initial concentrations of the substrates are the coefficients in the power
      series.

PMID- 28507670
TI  - Simultaneous construction of two linkages for the on-surface synthesis of imine
      boroxine hybrid covalent organic frameworks.
AB  - The orthogonality between the Schiff base reaction and the boronic acid
      dehydration reaction is explored during the on-surface synthesis process. By
      activating the above two reactions in one-step and employing asymmetrical
      substituted monomers and the 3-fold symmetric monomer 1,3,5-tris(4
      aminophenyl)benzene (TAPB), highly ordered imine-boroxine hybrid single-layered
      covalent organic frameworks (sCOFs) have been successfully constructed on HOPG by
      a gas-solid interface reaction method and characterized by scanning tunnelling
      microscopy (STM). In particular, the reaction between the meta-substituted
      monomer and TAPB generates sCOFB with a windmill structure, which is the first
      sCOF with surface chirality so far reported. The demonstration of the one-step
      synthesis of multiple linkages to form sCOFs can further enlarge the sCOF family
      and expand the design routes for functional 2D organic nanomaterials.

PMID- 28507671
TI  - CO/O2 assisted oxidative carbon-carbon and carbon-heteroatom bond cleavage for
      the synthesis of oxosulfonates from DMSO and olefins.
AB  - Selective carbon-carbon and carbon-heteroatom bond cleavage was achieved in a one
      reaction system. With this strategy a novel Pd/Cu-catalyzed aerobic oxidative
      oxosulfonation of olefins with DMSO has been developed. Preliminary mechanistic
      investigations indicated that CO/O2 assisted the bond cleavage and the leaving
      groups from the starting materials were trapped by O2 and underwent a
      hydroxylation process.

PMID- 28507672
TI  - Mechanism of photocatalytic water oxidation on small TiO2 nanoparticles.
AB  - We present the first unconstrained nonadiabatic molecular dynamics (NAMD)
      simulations of photocatalytic water oxidation by small hydrated TiO2
      nanoparticles using Tully surface hopping and time-dependent density functional
      theory. The results indicate that ultrafast electron-proton transfer from
      physisorbed water to the photohole initiates the photo-oxidation on the S1
      potential energy surface. The new mechanism readily explains the observation of
      mobile hydroxyl radicals in recent experiments. Two key driving forces for the
      photo-oxidation reaction are identified: localization of the electron-hole pair
      and stabilization of the photohole by hydrogen bonding interaction. Our findings
      illustrate the scope of recent advances in NAMD methods and emphasize the
      importance of explicit simulation of electronic excitations.

PMID- 28507674
TI  - Highly specific C-C bond cleavage induced FRET fluorescence for in vivo
      biological nitric oxide imaging.
AB  - A novel Forster resonance energy transfer (FRET) fluorescence "off-on" system
      based on the highly specific, sensitive and effective C-C bond cleavage of
      certain dihydropyridine derivatives was reported for real-time quantitative
      imaging of nitric oxide (NO). 1,4-Dihydropyridine was synthesized as a novel
      linker which could connect customized fluorophores and their corresponding
      quenchers. The specific and quantitative response to NO is confirmed using
      fluorescence spectrometry with the classical example of fluorescein
      isothiocyanate (FITC) and [4'-(N,N'-dimethylamino)phenylazo] benzoyl (DABCYL).
      The fluorescence intensity increased linearly with the increase in the amount of
      NO. Cells incubated with an exogenous NO donor emitted fluorescence as expected.
      A high fluorescence intensity was detected in macrophages which generate NO when
      incubated with lipopolysaccharide (LPS). The in vivo imaging shows about an 8
      fold contrast between Freund's adjuvant stimulated feet and normal feet in mice
      after intravenous injection, which was the first example of in vivo
      semiquantitative fluorescence imaging of NO in mammals.

PMID- 28507673
TI  - AIEgen-based theranostic system: targeted imaging of cancer cells and adjuvant
      amplification of antitumor efficacy of paclitaxel.
AB  - Photosensitizers are generally treated as key components for photodynamic
      therapy. In contrast, we herein report an aggregation-induced emission luminogen
      (AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic
      adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer
      drug, with a synergistic effect of "0 + 1 > 1". Besides the adjuvant function,
      TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in
      cancer cells in a fluorescence turn-on mode, by taking advantage of the specific
      YSA peptide (YSAYPDSVPMMS)-EphA2 protein interaction. The simple incorporation of
      FFG as a self-assembly-aided unit between AIEgen (TPE-Py) and YSA significantly
      enhances the fluorescent signal output of TPE-Py when imaging EphA2 clusters in
      live cancer cells. Cytotoxicity and western blot studies reveal that the reactive
      oxygen species (ROS) generated by TPE-Py-FFGYSA upon exposure to light do not
      kill cancer cells, but instead provide an intracellular oxidative environment to
      help paclitaxel have much better efficacy. This study thus not only extends the
      application scope of photosensitizers, but also offers a unique theranostic
      system with the combination of diagnostic imaging and adjuvant antitumor therapy.

PMID- 28507675
TI  - Psychosine variants as antigens for natural killer T cells.
AB  - Natural killer T (NKT) cells play a central role in the interface between innate
      and adaptive immunity, and alpha-galactosylceramide was recently shown to be an
      endogenous antigen for these cells. The source of alpha-galactosylceramide has
      not yet been determined; however, in vivo degradation of alpha-galactosylceramide
      involves generation of alpha-psychosine (alpha-galactosylsphingosine). Alpha
      psychosine stimulates cytokine release from NKT cells and constitutes an
      endogenous antigen for these cells. Alpha-psychosine contains a single lipid
      chain, while most antigens for NKT cells have two lipid chains, and we have
      investigated if other glycolipids with one lipid chain, derived from know
      antigens for NKT cells, stimulate cytokine release from NKT cells. Only
      psychosine variants derived from the most potent NKT cell antigens cause
      stimulation, and this stimulation occurs in vitro as well as in vivo. Truncated
      forms of weak antigens for NKT cells are not stimulatory.

PMID- 28507676
TI  - Formation mechanism of overlapping grain boundaries in graphene chemical vapor
      deposition growth.
AB  - The formation of grain boundaries (GBs) in graphene films is both fundamentally
      interesting and practically important for many applications. A GB in graphene is
      known as a linear defect and is formed during the coalescence of two single
      crystalline graphene domains. The covalent binding between domains is broadly
      known as the mechanism of GB formation during graphene chemical vapor deposition
      (CVD) growth. Here, we demonstrate another GB formation mechanism, where two
      graphene domains are connected by weak van der Waals interactions between
      overlapping graphene layers. The formation mechanism of the overlapping GBs
      (OLGBs) is systematically explored theoretically and the proposed conditions for
      forming OLGBs are validated by experimental observations. This discovery leads to
      a deep understanding of the mechanism of graphene CVD growth and reveals
      potential means for graphene quality control in CVD synthesis.

PMID- 28507677
TI  - Pentafluorobenzene end-group as a versatile handle for para fluoro "click"
      functionalization of polythiophenes.
AB  - A convenient method of introducing pentafluorobenzene (PFB) as a single end-group
      in polythiophene derivatives is reported via in situ quenching of the
      polymerization. We demonstrate that the PFB-group is a particularly useful end
      group due to its ability to undergo fast nucleophilic aromatic substitutions.
      Using this molecular handle, we are able to quantitatively tether a variety of
      common nucleophiles to the polythiophene backbone. The mild conditions required
      for the reaction allows sensitive functional moieties, such as biotin or a cross
      linkable trimethoxysilane, to be introduced as end-groups. The high yield enabled
      the formation of a diblock rod-coil polymer from equimolar reactants under
      transition metal-free conditions at room temperature. We further demonstrate that
      water soluble polythiophenes end-capped with PFB can be prepared via the
      hydrolysis of an ester precursor, and that such polymers are amenable to
      functionalization under aqueous conditions.

PMID- 28507678
TI  - Prediction of superconducting iron-bismuth intermetallic compounds at high
      pressure.
AB  - The synthesis of materials in high-pressure experiments has recently attracted
      increasing attention, especially since the discovery of record breaking
      superconducting temperatures in the sulfur-hydrogen and other hydrogen-rich
      systems. Commonly, the initial precursor in a high pressure experiment contains
      constituent elements that are known to form compounds at ambient conditions,
      however the discovery of high-pressure phases in systems immiscible under ambient
      conditions poses an additional materials design challenge. We performed an
      extensive multi component ab initio structural search in the immiscible Fe-Bi
      system at high pressure and report on the surprising discovery of two stable
      compounds at pressures above ~36 GPa, FeBi2 and FeBi3. According to our
      predictions, FeBi2 is a metal at the border of magnetism with a conventional
      electron-phonon mediated superconducting transition temperature of Tc = 1.3 K at
      40 GPa.

PMID- 28507679
TI  - [Ag115S34(SCH2C6H4t Bu)47(dpph)6]: synthesis, crystal structure and NMR
      investigations of a soluble silver chalcogenide nanocluster.
AB  - With the aim to synthesize soluble cluster molecules, the silver salt of (4-(tert
      butyl)phenyl)methanethiol [AgSCH2C6H4t Bu] was applied as a suitable precursor
      for the formation of a nanoscale silver sulfide cluster. In the presence of 1,6
      (diphenylphosphino)hexane (dpph), the 115 nuclear silver cluster
      [Ag115S34(SCH2C6H4t Bu)47(dpph)6] was obtained. The molecular structure of this
      compound was elucidated by single crystal X-ray analysis and fully characterized
      by spectroscopic techniques. In contrast to most of the previously published
      cluster compounds with more than a hundred heavy atoms, this nanoscale inorganic
      molecule is soluble in organic solvents, which allowed a comprehensive
      investigation in solution by UV-Vis spectroscopy and one- and two-dimensional NMR
      spectroscopy including 31P/109Ag-HSQC and DOSY experiments. These are the first
      heteronuclear NMR investigations on coinage metal chalcogenides. They give some
      first insight into the behavior of nanoscale silver sulfide clusters in solution.
      Additionally, molecular weight determinations were performed by 2D analytical
      ultracentrifugation and HR-TEM investigations confirm the presence of size
      homogeneous nanoparticles present in solution.

PMID- 28507680
TI  - An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved
      anticancer activity in vivo.
AB  - The design of targeted platinum(iv) prodrugs is a very promising approach to
      enhance the low selectivity of platinum(ii) drugs towards cancerous tissue in
      order to reduce the impact on healthy tissue and, consequently, the often severe
      side-effects. Herein, we report a set of mono-functionalized cis- and oxaliplatin
      based platinum(iv) complexes bearing a maleimide moiety, which allows selective
      binding to serum albumin in the bloodstream. This leads not only to a prolonged
      plasma half-life by avoidance of fast renal clearance, but also to preferential
      accumulation of the drug in the tumor tissue due to the EPR-effect. Additionally,
      analogous succinimide-functionalized derivatives were prepared to verify the
      influence of the maleimide moiety. First experiments showed that all the
      maleimide compounds are stable and also possess good albumin-binding properties
      in whole serum. Further analytical studies on in vivo samples proved the highly
      increased plasma half-life, as well as tumor accumulation of the maleimide
      functionalized substances. In vivo antitumor experiments with CT-26-bearing mice
      showed that, in contrast to the cisplatin derivatives, the oxaliplatin-based
      complexes had exceptionally better activity than the free drug resulting in the
      cure of the majority of treated mice. Subsequent analysis suggested that a
      distinctly faster reduction as well as reduced tumor accumulation of the
      cisplatin derivative might explain the worse performance compared to the
      oxaliplatin(iv) complexes. Taken together, a novel lead platinum(iv) complex with
      outstanding antitumor activity is presented, which will now be further developed
      towards clinical phase I trials.

PMID- 28507682
TI  - SABRE hyperpolarisation of vitamin B3 as a function of pH.
AB  - In this work we describe how the signal enhancements obtained through the SABRE
      process in methanol-d4 solution are significantly affected by pH. Nicotinic acid
      (vitamin B3, NA) is used as the agent, and changing pH is shown to modify the
      level of polarisation transfer by over an order of magnitude, with significant
      improvements being seen in terms of the signal amplitude and relaxation rate at
      high pH values. These observations reveal that manipulating pH to improve SABRE
      enhancements levels may improve the potential of this method to quantify low
      concentrations of analytes in mixtures. 1H NMR spectroscopy results link this
      change to the form of the SABRE catalyst, which changes with pH, resulting in
      dramatic changes in the magnitude of the ligand exchange rates. The presented
      data also uses the fact that the chemical shifts of the nicotinic acids NMR
      resonances are affected by pH to establish that hyperpolarised 1H-based pH
      mapping with SABRE is possible. Moreover, the strong polarisation transfer field
      dependence shown in the amplitudes of the associated higher order longitudinal
      terms offers significant opportunities for the rapid detection of hyperpolarised
      NA in H2O itself without solvent suppression. 1H and 13C MRI images of
      hyperpolarised vitamin B3 in a series of test phantoms are presented that show pH
      dependent intensity and contrast. This study therefore establishes that when the
      pH sensitivity of NA is combined with the increase in signal gain provided for by
      SABRE hyperpolarisation, a versatile pH probe results.

PMID- 28507681
TI  - Complementary oligonucleotides regulate induced fit ligand binding in duplexed
      aptamers.
AB  - Duplexed aptamers (DAs) are engineered by hybridizing an aptamer-complementary
      element (ACE, e.g. a DNA oligonucleotide) to an aptamer; to date, ACEs have been
      presumed to sequester the aptamer into a non-binding duplex state, in line with a
      conformational selection-based model of ligand binding. Here, we uncover that DAs
      can actively bind a ligand from the duplex state through an ACE-regulated induced
      fit mechanism. Using a widely-studied ATP DNA aptamer and a solution-based
      equilibrium assay, DAs were found to exhibit affinities up to 1 000 000-fold
      higher than predicted by conformational selection alone, with different ACEs
      regulating the level of induced fit binding, as well as the cooperative allostery
      of the DA (Hill slope of 1.8 to 0.7). To validate these unexpected findings, we
      developed a non-equilibrium surface-based assay that only signals induced fit
      binding, and corroborated the results from the solution-based assay. Our findings
      indicate that ACEs regulate ATP DA ligand binding dynamics, opening new avenues
      for the study and design of ligand-responsive nucleic acids.

PMID- 28507683
TI  - Supramolecular assembly of platinum-containing polyhedral oligomeric
      silsesquioxanes: an interplay of intermolecular interactions and a correlation
      between structural modifications and morphological transformations.
AB  - A series of alkynylplatinum(ii) terpyridine complexes functionalized with
      polyhedral oligomeric silsesquioxane (POSS) moieties has been demonstrated to
      exhibit drastic color changes and give various distinctive nanostructures with
      interesting multi-stage morphological transformations from spheres to nanoplates
      in response to solvent conditions through the interplay of various intermolecular
      interactions, including hydrophilic-hydrophilic, hydrophobic-hydrophobic, Pt...Pt
      and pi-pi stacking interactions. These supramolecular architectures can be
      systematically modified and controlled through the molecular design and the
      variation of solvent compositions. In particular, drastic changes in color in
      response to solvent polarity were observed through the incorporation of the
      charged moieties, representing a new class of potential candidates for functional
      materials with sensing or imaging capabilities. This class of complexes has been
      studied by 1H NMR spectroscopy, electron microscopy, UV-vis absorption and
      emission spectroscopy.

PMID- 28507684
TI  - Synthesis and reactivity of a ruthenocene-type complex bearing an aromatic pi
      ligand with the heaviest group 14 element.
AB  - An anionic ruthenocene derived from a dilithioplumbole complex was prepared. In
      the complex, the plumbole ligand coordinates a ruthenium atom in an eta5-fashion,
      similar to the cyclopentadienyl ligand in ferrocene. The ruthenocene that has the
      aromatic pi-ligand with the heaviest group 14 element reacted with electrophiles
      to afford the plumbole complexes wherein the plumbole ligands show deviation from
      planarity, in contrast to the planar plumbole ring in the anionic ruthenocene.
      The bent angles of the plumbole ligands are dependent on the substituents on the
      lead atoms. Cyclic voltammetry measurements revealed that the plumbole complexes
      are oxidized more easily than the corresponding stannole complexes.

PMID- 28507685
TI  - Design of a thermally controlled sequence of triazolinedione-based click and
      transclick reactions.
AB  - The reaction of triazolinediones (TADs) and indoles is of particular interest for
      polymer chemistry applications, as it is a very fast and irreversible additive
      free process at room temperature, but can be turned into a dynamic covalent bond
      forming process at elevated temperatures, giving a reliable bond exchange or
      'transclick' reaction. In this paper, we report an in-depth study aimed at
      controlling the TAD-indole reversible click reactions through rational design of
      modified indole reaction partners. This has resulted in the identification of a
      novel class of easily accessible indole derivatives that give dynamic TAD-adduct
      formation at significantly lower temperatures. We further demonstrate that these
      new substrates can be used to design a directed cascade of click reactions of a
      functionalized TAD moiety from an initial indole reaction partner to a second
      indole, and finally to an irreversible reaction partner. This controlled sequence
      of click and transclick reactions of a single TAD reagent between three different
      substrates has been demonstrated both on small molecule and macromolecular level,
      and the factors that control the reversibility profiles have been rationalized
      and guided by mechanistic considerations supported by theoretical calculations.

PMID- 28507687
TI  - A mild catalytic system for radical conjugate addition of nitrogen heterocycles.
AB  - The direct addition of pyridine and diazine units to electron-poor alkenes has
      been achieved via a redox radical mechanism that is enabled by limiting the
      effective concentration of the hydrogen-atom source. The described method is
      tolerant of acidic functional groups and is generally applicable to the union of
      a wide range of Michael acceptors and 6-membered heterocyclic halides.

PMID- 28507686
TI  - Gas confinement in compartmentalized coordination polymers for highly selective
      sorption.
AB  - Discrimination between different gases is an essential aspect for industrial and
      environmental applications involving sensing and separation. Several classes of
      porous materials have been used in this context, including zeolites and more
      recently MOFs. However, to reach high selectivities for the separation of gas
      mixtures is a challenging task that often requires the understanding of the
      specific interactions established between the porous framework and the gases.
      Here we propose an approach to obtain an enhanced selectivity based on the use of
      compartmentalized coordination polymers, named CCP-1 and CCP-2, which are
      crystalline materials comprising isolated discrete cavities. These
      compartmentalized materials are excellent candidates for the selective separation
      of CO2 from methane and nitrogen. A complete understanding of the sorption
      process is accomplished with the use of complementary experimental techniques
      including X-ray diffraction, adsorption studies, inelastic- and quasi-elastic
      neutron scattering, magnetic measurements and molecular dynamics calculations.

PMID- 28507688
TI  - Donor-acceptor stacking arrangements in bulk and thin-film high-mobility
      conjugated polymers characterized using molecular modelling and MAS and surface
      enhanced solid-state NMR spectroscopy.
AB  - Conjugated polymers show promising properties as cheap, sustainable and solution
      processable semiconductors. A key challenge in the development of these materials
      is to determine the polymer chain structure, conformation and packing in both the
      bulk polymer and in thin films typically used in devices. However, many
      characterisation techniques are unable to provide atomic-level structural
      information owing to the presence of disorder. Here, we use molecular modelling,
      magic-angle spinning (MAS) and dynamic nuclear polarisation surface-enhanced NMR
      spectroscopy (DNP SENS) to characterise the polymer backbone group conformations
      and packing arrangement in the high-mobility donor-acceptor copolymer
      diketopyrrolo-pyrrole-dithienylthieno[3,2-b]thiophene (DPP-DTT). Using
      conventional 1H and 13C solid-state MAS NMR coupled with density functional
      theory calculations and molecular dynamics simulations, we find that the bulk
      polymer adopts a highly planar backbone conformation with a laterally-shifted
      donor-on-acceptor stacking arrangement. DNP SENS enables acquisition of 13C NMR
      data for polymer films, where sensitivity is limiting owing to small sample
      volumes. The DNP signal enhancement enables a two-dimensional 1H-13C HETCOR
      spectrum to be recorded for a drop-cast polymer film, and a 13C CPMAS NMR
      spectrum to be recorded for a spin-coated thin-film with a thickness of only 400
      nm. The results show that the same planar backbone structure and intermolecular
      stacking arrangement is preserved in the films following solution processing and
      annealing, thereby rationalizing the favourable device properties of DPP-DTT, and
      providing a protocol for the study of other thin film materials.

PMID- 28507689
TI  - Tuning the separation and coupling of corannulene trianion-radicals through
      sizable alkali metal belts.
AB  - The first heterobimetallic sandwich-type aggregate formed by bowl-shaped
      corannulene trianion-radicals, C20H103-, has been synthesized using mixed-metal
      reduction of C20H10. The product was crystallographically characterized to reveal
      the self-assembly of [Cs+//(C20H103-)/4K+/(C20H103-)//Cs+], in which two triply
      charged corannulene decks encapsulate a rectangle of four potassium ions (the
      K...K separations are 4.212(4) and 5.185(4) A), with the exterior concave bowl
      cavities being selectively filled by one cesium ion each. In order to provide
      insights into the geometrical features and electronic structure of this novel
      mixed-metal organometallic self-assembly, an in-depth theoretical investigation
      has been carried out. Specifically, the influence of internal metal binding on
      the geometry and magnetic coupling of C20H103- radicals is investigated for Group
      1 metals. This study reveals that replacement of the sandwiched potassium ions
      with larger (Cs) and smaller (Li) ions allows variation of the size of the
      encapsulated metal belts, and thus enables tuning of the coupling of C20H103-
      radicals.

PMID- 28507690
TI  - A bifunctional cerium phosphate catalyst for chemoselective acetalization.
AB  - Acid-base solid catalysts synthesized with structurally controlled uniform active
      sites can lead to unique catalysis. In this study, a CePO4 catalyst was
      synthesized using a hydrothermal method and found to exhibit high catalytic
      performance for the chemoselective acetalization of 5-hydroxymethylfurfural with
      alcohols, in sharp contrast to other homogeneous and heterogeneous acid and/or
      base catalysts. In the presence of CePO4, various combinations of carbonyl
      compounds and alcohols are efficiently converted into the corresponding acetal
      derivatives in good to excellent yields. Mechanistic studies show that CePO4 most
      likely acts as a bifunctional catalyst through the interaction of uniform Lewis
      acid and weak base sites with 5-hydroxymethylfurfural and alcohol molecules,
      respectively, which results in high catalytic performance.

PMID- 28507691
TI  - Mechanism of resonant electron emission from the deprotonated GFP chromophore and
      its biomimetics.
AB  - The Green Fluorescent Protein (GFP), which is widely used in bioimaging, is known
      to undergo light-induced redox transformations. Electron transfer is thought to
      occur resonantly through excited states of its chromophore; however, a detailed
      understanding of the electron gateway states of the chromophore is still missing.
      Here, we use photoelectron spectroscopy and high-level quantum chemistry
      calculations to show that following UV excitation, the ultrafast electron
      dynamics in the chromophore anion proceeds via an excited shape resonance
      strongly coupled to the open continuum. The impact of this state is found across
      the entire 355-315 nm excitation range, from above the first bound-bound
      transition to below the opening of higher-lying continua. By disentangling the
      electron dynamics in the photodetachment channels, we provide an important
      reference for the adiabatic position of the electron gateway state, which is
      located at 348 nm, and discover the source of the curiously large widths of the
      photoelectron spectra that have been reported in the literature. By introducing
      chemical modifications to the GFP chromophore, we show that the detachment
      threshold and the position of the gateway state, and hence the underlying excited
      state dynamics, can be changed systematically. This enables a fine tuning of the
      intrinsic electron emission properties of the GFP chromophore and has significant
      implications for its function, suggesting that the biomimetic GFP chromophores
      are more stable to photooxidation.

PMID- 28507692
TI  - High-level ab initio potential energy surface and dynamics of the F- + CH3I SN2
      and proton-transfer reactions.
AB  - Bimolecular nucleophilic substitution (SN2) and proton transfer are fundamental
      processes in chemistry and F- + CH3I is an important prototype of these
      reactions. Here we develop the first full-dimensional ab initio analytical
      potential energy surface (PES) for the F- + CH3I system using a permutationally
      invariant fit of high-level composite energies obtained with the combination of
      the explicitly-correlated CCSD(T)-F12b method, the aug-cc-pVTZ basis, core
      electron correlation effects, and a relativistic effective core potential for
      iodine. The PES accurately describes the SN2 channel producing I- + CH3F via
      Walden-inversion, front-side attack, and double-inversion pathways as well as the
      proton-transfer channel leading to HF + CH2I-. The relative energies of the
      stationary points on the PES agree well with the new explicitly-correlated all
      electron CCSD(T)-F12b/QZ-quality benchmark values. Quasiclassical trajectory
      computations on the PES show that the proton transfer becomes significant at high
      collision energies and double-inversion as well as front-side attack trajectories
      can occur. The computed broad angular distributions and hot internal energy
      distributions indicate the dominance of indirect mechanisms at lower collision
      energies, which is confirmed by analyzing the integration time and leaving group
      velocity distributions. Comparison with available crossed-beam experiments shows
      usually good agreement.

PMID- 28507694
TI  - A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under
      semiaqueous conditions.
AB  - The 1,3,4-oxadiazole is an aromatic heterocycle valued for its low-lipophilicity
      in drug development. Substituents at the 2- and/or 5-positions can modulate the
      heterocycle's electronic and hydrogen bond-accepting capability, while exploiting
      its use as a carbonyl bioisostere. A new approach to 1,3,4-oxadiazoles is
      described wherein alpha-bromo nitroalkanes are coupled to acyl hydrazides to
      deliver the 2,5-disubstituted oxadiazole directly, avoiding a 1,2-diacyl
      hydrazide intermediate. Access to new building blocks of oxadiazole-substituted
      secondary amines is improved by leveraging chiral alpha-bromo nitroalkane or
      amino acid hydrazide substrates. The non-dehydrative conditions for oxadiazole
      synthesis are particularly notable, in contrast to alternatives reliant on highly
      oxophilic reagents to effect cyclization of unsymmetrical 1,2-diacyl hydrazides.
      The mild conditions are punctuated by the straightforward removal of co-products
      by a standard aqueous wash.

PMID- 28507693
TI  - Fluorocarbene, fluoroolefin, and fluorocarbyne complexes of Rh.
AB  - The manuscript reports the synthesis, characterization, and analysis of
      electronic structure in a series of complexes of small perfluorocarbon ligands
      with the (PNP)Rh fragment (where PNP is a diarylamido/bis(phosphine) pincer
      ligand). Reactions of (PNP)Rh(TBE) as the source of (PNP)Rh with CHF3 and C2HF5
      produced perfluoroalkylidene complexes (PNP)Rh 0000000000000000000000000000000000
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      0000000000000000000000000000000000 CF2 and (PNP)RhC(F)(CF3). (PNP)RhCF2 could
      also be obtained via the reaction of (PNP)Rh(TBE) with Me3SiCF3/CsF, with an
      admixture of (PNP)Rh(C2F4), where TBE = tert-butylethylene. Abstraction of
      fluoride from these neutral (PNP)RhC x F y complexes was successful, although
      only abstraction from (PNP)RhCF2 allowed unambiguous identification of the Rh
      product, [(PNP)Rh 0000000000000000000000000000000000
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      0000000000000000000000000000000000 CF]+. DFT computational studies allowed
      comparison of relative energies of (PNP)Rh(C2F4) and [(PNP)Rh(C2F3)]+ isomers as
      well as comparisons between the electronic structure of the CF2, C2F4, and CF+
      complexes and their hydrocarbon analogues.

PMID- 28507695
TI  - ANI-1: an extensible neural network potential with DFT accuracy at force field
      computational cost.
AB  - Deep learning is revolutionizing many areas of science and technology, especially
      image, text, and speech recognition. In this paper, we demonstrate how a deep
      neural network (NN) trained on quantum mechanical (QM) DFT calculations can learn
      an accurate and transferable potential for organic molecules. We introduce ANAKIN
      ME (Accurate NeurAl networK engINe for Molecular Energies) or ANI for short. ANI
      is a new method designed with the intent of developing transferable neural
      network potentials that utilize a highly-modified version of the Behler and
      Parrinello symmetry functions to build single-atom atomic environment vectors
      (AEV) as a molecular representation. AEVs provide the ability to train neural
      networks to data that spans both configurational and conformational space, a feat
      not previously accomplished on this scale. We utilized ANI to build a potential
      called ANI-1, which was trained on a subset of the GDB databases with up to 8
      heavy atoms in order to predict total energies for organic molecules containing
      four atom types: H, C, N, and O. To obtain an accelerated but physically relevant
      sampling of molecular potential surfaces, we also proposed a Normal Mode Sampling
      (NMS) method for generating molecular conformations. Through a series of case
      studies, we show that ANI-1 is chemically accurate compared to reference DFT
      calculations on much larger molecular systems (up to 54 atoms) than those
      included in the training data set.

PMID- 28507696
TI  - Highly chemoselective ruthenium(ii)-catalyzed direct arylation of cyclic and N,N
      dialkyl benzamides with aryl silanes.
AB  - The ruthenium(ii)-catalyzed oxidative cross-coupling of C(sp2)-H bonds with
      organosilanes has been accomplished for the first time. This novel protocol
      enlists challenging cyclic and N,N-dialkyl benzamides as weakly-coordinating
      substrates to achieve highly regioselective C(sp2)-H arylation as a proof-of
      concept, taking advantage of the attractive features of organosilanes as coupling
      partners. This innovative method is characterized by very high chemoselectivity,
      installing halide functional groups (I, Br, Cl) that are incompatible with Ru(ii)
      carboxylate systems employing halides as cross-coupling partners, while obviating
      the need for sensitive organometallic reagents and cryogenic temperatures typical
      to the classic directed-ortho-metallation (DoM) techniques, employing benzamides
      to afford bioactive structural motifs.

PMID- 28507698
TI  - Formicamycins, antibacterial polyketides produced by Streptomyces formicae
      isolated from African Tetraponera plant-ants.
AB  - We report a new Streptomyces species named S. formicae that was isolated from the
      African fungus-growing plant-ant Tetraponera penzigi and show that it produces
      novel pentacyclic polyketides that are active against MRSA and VRE. The chemical
      scaffold of these compounds, which we have called the formicamycins, is similar
      to the fasamycins identified from the heterologous expression of clones isolated
      from environmental DNA, but has significant differences that allow the scaffold
      to be decorated with up to four halogen atoms. We report the structures and
      bioactivities of 16 new molecules and show, using CRISPR/Cas9 genome editing,
      that biosynthesis of these compounds is encoded by a single type 2 polyketide
      synthase biosynthetic gene cluster in the S. formicae genome. Our work has
      identified the first antibiotic from the Tetraponera system and highlights the
      benefits of exploring unusual ecological niches for new actinomycete strains and
      novel natural products.

PMID- 28507697
TI  - Regulating the active species of Ni(OH)2 using CeO2: 3D CeO2/Ni(OH)2/carbon foam
      as an efficient electrode for the oxygen evolution reaction.
AB  - Three dimensional (3D) N, O and S doped carbon foam (NOSCF) is prepared as a
      substrate for in situ vertically grown Ni(OH)2 nanosheets. As designed
      Ni(OH)2/NOSCF possesses strong electrostatic interactions with OH- ions due to
      many C 0000000000000000000000000000000000 0000000000000000000000000000000000
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      existing in NOSCF, which can facilitate the formation of crucial NiOOH
      intermediates during the OER process. CeO2 nanoparticles (NPs) of ~3.3 nm in size
      are decorated on Ni(OH)2 nanosheets to design a highly efficient
      CeO2/Ni(OH)2/NOSCF electrocatalyst for the oxygen evolution reaction (OER). The
      CeO2 NP decorated Ni(OH)2/NOSCF not only exhibits a remarkably improved OER
      performance with an onset potential of 240 mV, outperforming most reported non
      noble metal based OER electrocatalysts, but also possesses a small Tafel slope of
      57 mV dec-1 and excellent stability under different overpotentials. The
      synergistic effect of producing more active species of NiIII/IV and accelerating
      the charge transfer for Ni(OH)2/NOSCF by the introduction of CeO2 NPs is also
      investigated. These results demonstrate the possibility of designing energy
      efficient OER catalysts with the assistance of earth abundant CeO2-based
      catalysts.

PMID- 28507699
TI  - Polylysine-grafted Au144 nanoclusters: birth and growth of a healthy surface
      plasmon-resonance-like band.
AB  - Poly(amino acid)-coated gold nanoparticles hold promise in biomedical
      applications, particularly because they combine the unique physicochemical
      properties of the gold core, excellent biocompatibility, and easy
      functionalization of the poly(amino acid)-capping shell. Here we report a novel
      method for the preparation of robust hybrid core-shell nanosystems consisting of
      a Au144 cluster and a densely grafted polylysine layer. Linear polylysine chains
      were grown by direct N-carboxyanhydride (NCA) polymerization onto ligands capping
      the gold nanocluster. The density of the polylysine chains and the thickness of
      the polymer layer strongly depend on the amount and concentration of the NCA
      monomer and the initiator. The optical spectra of the so-obtained core-shell
      nanosystems show a strong surface plasmon resonance (SPR)-like band at 531 nm. In
      fact, despite maintenance of the gold cluster size and the absence of
      interparticle aggregation, the polylysine-capped clusters behave as if they have
      a diameter nearly 4 times larger. To the best of our knowledge, this is the first
      observation of the growth of a fully developed, very stable SPR-like band for a
      gold nanocluster of such dimensions. The robust polylysine protective shell makes
      the nanoparticles very stable under conditions of chemical etching, in the
      presence of glutathione, and at different pH values, without gold core
      deshielding or alteration of the SPR-like band. This polymerization method can
      conceivably be extended to prepare core-shell nanosystems based on other mono- or
      co-poly(amino acids).

PMID- 28507700
TI  - Stepwise observation and quantification and mixed matrix membrane separation of
      CO2 within a hydroxy-decorated porous host.
AB  - The identification of preferred binding domains within a host structure provides
      important insights into the function of materials. State-of-the-art reports
      mostly focus on crystallographic studies of empty and single component guest
      loaded host structures to determine the location of guests. However, measurements
      of material properties (e.g., adsorption and breakthrough of substrates) are
      usually performed for a wide range of pressure (guest coverage) and/or using
      multi-component gas mixtures. Here we report the development of a multifunctional
      gas dosing system for use in X-ray powder diffraction studies on Beamline I11 at
      Diamond Light Source. This facility is fully automated and enables in situ
      crystallographic studies of host structures under (i) unlimited target gas
      loadings and (ii) loading of multi-component gas mixtures. A proof-of-concept
      study was conducted on a hydroxyl-decorated porous material MFM-300(VIII) under
      (i) five different CO2 pressures covering the isotherm range and (ii) the loading
      of equimolar mixtures of CO2/N2. The study has successfully captured the
      structural dynamics underpinning CO2 uptake as a function of surface coverage.
      Moreover, MFM-300(VIII) was incorporated in a mixed matrix membrane (MMM) with
      PIM-1 in order to evaluate the CO2/N2 separation potential of this material. Gas
      permeation measurements on the MMM show a great improvement over the bare PIM-1
      polymer for CO2/N2 separation based on the ideal selectivity.

PMID- 28507701
TI  - Peptide-templated noble metal catalysts: syntheses and applications.
AB  - Noble metal catalysts have been widely used in many applications because of their
      high activity and selectivity. However, a controllable preparation of noble metal
      catalysts still remains as a significant challenge. To overcome this challenge,
      peptide templates can play a critical role in the controllable syntheses of
      catalysts owing to their flexible binding with specific metallic surfaces and
      self-assembly characteristics. By employing peptide templates, the size, shape,
      facet, structure, and composition of obtained catalysts can all be specifically
      controlled under the mild synthesis conditions. In addition, catalysts with
      spherical, nanofiber, and nanofilm structures can all be produced by associating
      with the self-assembly characteristics of peptide templates. Furthermore, the
      peptide-templated noble metal catalysts also reveal significantly enhanced
      catalytic behaviours compared with conventional catalysts because the electron
      conductivity, metal dispersion, and reactive site exposure can all be improved.
      In this review, we summarize the research progresses in the syntheses of peptide
      templated noble metal catalysts. The applications of the peptide-templated
      catalysts in organic reactions, photocatalysis, and electrocatalysis are
      discussed, and the relationship between structure and activity of these catalysts
      are addressed. Future opportunities, including new catalytic materials designed
      by using biological principles, are indicated to achieve selective, eco-friendly,
      and energy neutral synthesis approaches.

PMID- 28507702
TI  - Plasmon-induced charge separation: chemistry and wide applications.
AB  - Recent development of nanoplasmonics has stimulated chemists to utilize plasmonic
      nanomaterials for efficient and distinctive photochemical applications, and
      physicists to boldly go inside the "wet" chemistry world. The discovery of
      plasmon-induced charge separation (PICS) has even accelerated these trends. On
      the other hand, some confusion is found in discussions about PICS. In this
      perspective, we focus on differences between PICS and some other phenomena such
      as co-catalysis effect and plasmonic nanoantenna effect. In addition, materials
      and nanostructures suitable for PICS are shown, and characteristics and features
      unique to PICS are documented. Although it is well known that PICS has been
      applied to photovoltaics and photocatalysis, here light is shed on other
      applications that take better advantage of PICS, such as chemical sensing and
      biosensing, various photochromisms, photoswitchable functionalities and nanoscale
      photofabrication.

PMID- 28507703
TI  - Advanced electroanalytical chemistry at nanoelectrodes.
AB  - Nanoelectrodes, with dimensions below 100 nm, have the advantages of high
      sensitivity and high spatial resolution. These electrodes have attracted
      increasing attention in various fields such as single cell analysis, single
      molecule detection, single particle characterization and high-resolution imaging.
      The rapid growth of novel nanoelectrodes and nanoelectrochemical methods brings
      enormous new opportunities in the field. In this perspective, we discuss the
      challenges, advances, and opportunities for nanoelectrode fabrication, real-time
      characterizations and high-performance electrochemical instrumentation.

PMID- 28507704
TI  - Elucidation of salicylate attachment in celesticetin biosynthesis opens the door
      to create a library of more efficient hybrid lincosamide antibiotics.
AB  - Lincosamides, which are produced by streptomycetes, compose a small but
      clinically important class of antibiotics. The recent elucidation of the
      condensation and post-condensation biosynthetic steps of the lincosamides
      lincomycin and celesticetin revealed several unexpected reaction mechanisms.
      Here, we prepared recombinant proteins involved in the celesticetin biosynthetic
      pathway and used them for in vitro assays that were monitored by LC-MS. Our
      results elucidate the last biosynthetic step of celesticetin: the attachment of
      salicylic acid is catalyzed by the Ccb2 acyl-CoA ligase and the Ccb1
      acyltransferase. Ccb1 belongs to the WS/DGAT protein family and, in contrast to
      the characterized members of the family, has unusual substrate specificity. To
      the best of our knowledge, Ccb1 is the first protein in this family that
      transfers a benzoyl derivative-CoA conjugate and is the first WS/DGAT protein
      involved in the biosynthesis of secondary metabolites. Furthermore, we exploited
      the relaxed substrate specificities of Ccb1 and Ccb2, as well as three additional
      upstream post-condensation biosynthetic proteins in the celesticetin pathway, and
      combined the lincomycin and the celesticetin biosynthetic pathways in vitro. In
      this way, we prepared a library of 150 novel hybrid lincosamides, including two
      unnatural chimeras of lincomycin and celesticetin, which were shown to have
      antibacterial properties more pronounced than clinically used lincomycin. These
      achievements may be considered a case study in applying knowledge about
      biosynthetic machinery to assemble a large number of compounds from originally a
      small group of natural products without the need for chemical synthesis.

PMID- 28507705
TI  - Acid- and Au(i)-mediated synthesis of hexathymidine-DNA-heterocycle chimeras, an
      efficient entry to DNA-encoded libraries inspired by drug structures.
AB  - Libraries of DNA-tagged compounds are a validated screening technology for drug
      discovery. They are synthesized through combinatorial iterations of alternated
      coding and preparative synthesis steps. Thus, large chemical space can be
      accessed for target-based screening. However, the need to preserve the
      functionality of the DNA tag severely restricts the choice of chemical methods
      for library synthesis. Acidic organocatalysts, transition metals, and oxidants
      furnish diverse drug-like structures from simple starting materials, but cause
      loss of genetic information by depurination. A hexathymidine oligonucleotide,
      called "hexT" allows the chemist utilizing these classes of catalysts to access a
      potentially broad variety of structures in the initial step of library synthesis.
      We exploited its catalyst tolerance to efficiently synthesize diverse substituted
      beta-carbolines, pyrazolines, and pyrazoles from readily available starting
      materials as hexT conjugates by acid- and Au(i)-catalysis, respectively. The hexT
      conjugates were ligated to coding DNA sequences yielding encoded screening
      libraries inspired by drug structures.

PMID- 28507706
TI  - pH- and ligand-induced release of loads from DNA-acrylamide hydrogel
      microcapsules.
AB  - Herein, a method to construct stimuli-responsive DNA-acrylamide-based hydrogel
      microcapsules has been presented. This method involves the use of polyacrylamide
      chains modified with predesigned nucleic acid hairpin units and optionally single
      strand tethers that provide the required hybridization and recognition functions
      to yield substrate-loaded stimuli-responsive hydrogel-based microcapsules. The
      synthesis of the microcapsules involves the loading of CaCO3 microparticles with
      the respective load substrates and the functionalization of the CaCO3 template
      particles with nucleic acid promoter units. In the presence of the hairpin
      modified acrylamide chains, the promoter units induce the hybridization chain
      reaction (HCR), which leads to the formation of a hydrogel coating, which, after
      the dissociation of the CaCO3 cores, yields substrate-loaded stimuli-responsive
      hydrogel microcapsules. One of the microcapsule systems includes, in the hairpin
      modified acrylamide constructs, and in the subsequent HCR-generated hydrogel
      shells, the caged sequences of anti-ATP or anti-cocaine aptamers. In the presence
      of ATP or cocaine, the duplex-caged aptamer sequences are separated via the
      formation of ATP- or cocaine-aptamer complexes, which results in the partial
      separation of the microcapsules and the release of the loads. The second type of
      microcapsule is cooperatively stabilized by bridges generated by HCR and pH
      sensitive duplex units. Under acidic conditions, the pH-sensitive bridges
      dissociate via the formation of i-motif structures, which results in an increase
      in the fluidity of the microcapsule shells and the release of the loads.
      Preliminary studies indicate that ATP- or pH-responsive microcapsules loaded with
      the anticancer drug, doxorubicin, have a selective cytotoxic effect on MDA-MB-231
      cancer cells.

PMID- 28507708
TI  - Manganese-catalyzed allylation via sequential C-H and C-C/C-Het bond activation.
AB  - Manganese-catalyzed sequential C-H and C-C/C-Het bond activation to synthesize
      allylic alcohols, allylated arenes, functionalized cyclopentenes and skipped
      dienes is reported. This protocol can be readily scaled up and various coupling
      partners are applied in manganese catalysis for the first time. Moreover,
      manganese-catalyzed alkenyl C(sp2)-H activation is also shown. Complimentary to
      the standard solution-based protocols, these reactions also proceed efficiently
      under neat conditions, which is unprecedented for abundant metal catalyzed C-H
      activation reactions.

PMID- 28507707
TI  - Nanophase-separated Ni3Nb as an automobile exhaust catalyst.
AB  - Catalytic remediation of automobile exhaust has relied on precious metals (PMs)
      including platinum (Pt). Herein, we report that an intermetallic phase of Ni and
      niobium (Nb) (i.e., Ni3Nb) exhibits a significantly higher activity than that of
      Pt for the remediation of the most toxic gas in exhaust (i.e., nitrogen monoxide
      (NO)) in the presence of carbon monoxide (CO). When subjected to the exhaust
      remediation atmosphere, Ni3Nb spontaneously evolves into a catalytically active
      nanophase-separated structure consisting of filamentous Ni networks (thickness <
      10 nm) that are incorporated in a niobium oxide matrix (i.e., NbO x (x < 5/2)).
      The exposure of the filamentous Ni promotes NO dissociation, CO oxidation and N2
      generation, and the NbO x matrix absorbs excessive nitrogen adatoms to retain the
      active Ni0 sites at the metal/oxide interface. Furthermore, the NbO x matrix
      immobilizes the filamentous Ni at elevated temperatures to produce long-term and
      stable catalytic performance over hundreds of hours.

PMID- 28507709
TI  - First total synthesis of concavine.
AB  - The synthesis of the unusual alkaloid concavine, isolated from Clitocybe concava
      (Basidiomycetae), has been accomplished. The synthetic route features regio- and
      stereoselective manipulation of polycyclic imide intermediates via enolate
      substitution and Grignard addition, along with a key bridge-forming step
      involving a new method for sulfenylative radical cyclisation. The NMR data for
      synthetic concavine demonstrate that the original data reported for the natural
      product refer to the derived acetic acid salt, probably formed as an artefact of
      isolation or purification.

PMID- 28507711
TI  - Interfacial engineering of renewable metal organic framework derived honeycomb
      like nanoporous aluminum hydroxide with tunable porosity.
AB  - Novel honeycomb-like mesoporous aluminum hydroxide (pATH) was synthesized via a
      facile one-step reaction by employing ZIF-8 as a template. This self-decomposing
      template was removed automatically under acidic conditions without the need for
      any tedious or hazardous procedures. Meanwhile, the pore size of pATH was easily
      modulated by tuning the dimensions of the ZIF-8 polyhedrons. Of paramount
      importance was the fact that the dissolved ZIF-8 in solution was regenerated upon
      deprotonation of the ligand under mild alkali conditions, and was reused in the
      preparation of pATH, thus forming a delicate synthesis cycle. The renewable
      template conferred cost-effective and sustainable features to the as-synthesized
      product. As a proof-of-concept application, the fascinating nanoporous structure
      enabled pATH to load more phosphorous-containing flame retardant and endowed
      better interaction with epoxy resin over that of commercial aluminum hydroxide.
      The limiting oxygen index, UL-94 vertical burning test and cone calorimeter test
      showed that the results of epoxy with the modified pATH rivalled those of epoxy
      with two times the loading amount of the commercial counterpart, while the former
      presented better mechanical properties. The proposed "amorphous replica method"
      used in this work will advance the potential for launching a vast area of
      research and technology development for the preparation of porous metal
      hydroxides for use in practical applications.

PMID- 28507710
TI  - Semiconducting polymer dots with bright narrow-band emission at 800 nm for
      biological applications.
AB  - The development of near-infrared (NIR) fluorescent probes is critical for in vivo
      exploration of the fundamental and complex processes in living systems by
      noninvasive fluorescence imaging techniques. Semiconducting polymer dots (Pdots)
      are emerging as important probes that exhibit several advantages, such as high
      brightness and biocompatibility. However, NIR-emitting Pdots are very rare,
      particularly at the center (~800 nm) of the first optical window of biological
      tissues (between 650 nm and 950 nm). In this paper, we describe the synthesis of
      a semiconducting polymer with bright and narrow-band emission at 800 nm. The
      polymer was designed by incorporating a NIR porphyrin unit into a conjugated
      backbone; the polymer used a cascade energy transfer to produce the signal. The
      resulting Pdots possessed a narrow emission bandwidth (FWHM ~ 23 nm) and good
      fluorescence quantum yield (QY = 8%), which is high for a near-IR emitter. The
      Pdots were bioconjugated with streptavidin for specific labeling of cellular
      targets, yielding higher staining index when compared with commercial NIR probes,
      such as PE-Cy7. Moreover, the NIR polymer was combined with a long-wavelength
      absorbing polymer to make bright Pdots (QY = 15%) for in vivo noninvasive
      imaging. These NIR Pdots with surface PEGylation led to high-contrast imaging of
      lymph nodes and tumors in a mouse model. This work highlights the great potential
      of the NIR Pdots for cellular and in vivo imaging applications.

PMID- 28507712
TI  - Redox non-innocence permits catalytic nitrene carbonylation by (dadi)Ti
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      adamantyl).
AB  - Application of the diamide, diimine {-CHN(1,2-C6H4)N(2,6-iPr2-C6H3)}2m ((dadi) m
      ) ligand to titanium provided adducts (dadi)TiL x (1-L x ; L x = THF, PMe2Ph,
      (CNMe)2), which possess the redox formulation [(dadi)4-]Ti(iv)L x , and 22 pie-
      (4n + 2). Related complexes containing titanium-ligand multiple bonds, (dadi)TiX
      (2 X; X = O, NAd), exhibit a different dadi redox state, [(dadi)2-]Ti(iv)X,
      consistent with 20 pie- (4n). The Redox Non-Innocence (RNI) displayed by dadi m
      impedes binding by CO, and permits catalytic conversion of AdN3 + CO to AdNCO +
      N2. Kinetics measurements support carbonylation of 2 NAd as the rate determining
      step. Structural and computational evidence for the observed RNI is provided.

PMID- 28507713
TI  - White-light emission from discrete heterometallic lanthanide-directed self
      assembled complexes in solution.
AB  - White-light-emitting materials have attracted significant interest in recent
      years due to their potential applications in solid-state lighting and flat-panel
      displays. Design of such materials is challenging and often relies on the use of
      multiple fluorophores despite the fact that single component systems yield
      materials with enhanced stability and reproducibility. Herein, we have developed
      a white-light-emitting system based on the formation of discrete lanthanide-based
      self-assembled complexes using a newly-designed ligand. We demonstrate that fine
      tuning of the lanthanide ions molar ratio in the self-assemblies combined with
      the intrinsic blue fluorescence of the ligand allows for the successful emission
      of pure white light with CIE coordinates of (0.33, 0.34).

PMID- 28507714
TI  - Targeting the tumour microenvironment with an enzyme-responsive drug delivery
      system for the efficient therapy of breast and pancreatic cancers.
AB  - The development of novel therapeutic strategies allowing the destruction of
      tumour cells while sparing healthy tissues is one of the main challenges of
      cancer chemotherapy. Here, we report on the design and antitumour activity of a
      low-molecular-weight drug delivery system programmed for the selective release of
      the potent monomethylauristatin E in the tumour microenvironment of solid
      tumours. After intravenous administration, this compound binds covalently to
      plasmatic albumin through Michael addition, thereby enabling its passive
      accumulation in tumours where extracellular beta-glucuronidase initiates the
      selective release of the drug. This targeting device produces outstanding
      therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours
      in mice (50% and 33% of mice with the respective tumours cured), leading to
      impressive reduction or even disappearance of tumours without inducing side
      effects.

PMID- 28507715
TI  - A quantitative mechanistic PK/PD model directly connects Btk target engagement
      and in vivo efficacy.
AB  - Correlating target engagement with in vivo drug activity remains a central
      challenge in efforts to improve the efficiency of drug discovery. Previously we
      described a mechanistic pharmacokinetic-pharmacodynamic (PK/PD) model that used
      drug-target binding kinetics to successfully predict the in vivo efficacy of
      antibacterial compounds in models of Pseudomonas aeruginosa and Staphylococcus
      aureus infection. In the present work we extend this model to quantitatively
      correlate the engagement of Bruton's tyrosine kinase (Btk) by the covalent
      inhibitor CC-292 with the ability of this compound to reduce ankle swelling in an
      animal model of arthritis. The modeling studies include the rate of Btk turnover
      and reveal the vulnerability of Btk to engagement by CC-292.

PMID- 28507716
TI  - Chemistry in nanoconfined water.
AB  - Nanoconfined liquids have extremely different properties from the bulk, which
      profoundly affects chemical reactions taking place in nanosolvation. Here, we
      present extensive ab initio simulations of a vast set of chemical reactions
      within a water lamella that is nanoconfined by mineral surfaces, which might be
      relevant to prebiotic peptide formation in aqueous environments. Our results
      disclose a rich interplay of distinct effects, from steric factors typical of
      reactions occurring in small spaces to a charge-stabilization effect in
      nanoconfined water at extreme conditions similar to that observed in bulk water
      when changing from extreme to ambient conditions. These effects are found to
      modify significantly not only the energetics but also the mechanisms of reactions
      happening in nanoconfined water in comparison to the corresponding bulk regime.

PMID- 28507717
TI  - Dynamic, structural and thermodynamic basis of insulin-like growth factor 1
      kinase allostery mediated by activation loop phosphorylation.
AB  - Despite the importance of kinases' catalytic activity regulation in cell
      signaling, detailed mechanisms underlying their activity regulation are poorly
      understood. Herein, using insulin-like growth factor 1 receptor kinase (IGF-1RK)
      as a model, the mechanisms of kinase regulation by its activation loop (A-loop)
      phosphorylation were investigated through molecular dynamics (MD) and alchemical
      free energy simulations. Analyses of the simulation results and free energy
      landscapes determined for the entire catalytic cycle of the kinase revealed that
      A-loop phosphorylation affects each step in the IGF-1RK catalytic cycle,
      including conformational change, substrate binding/product release and catalytic
      phosphoryl transfer. Specifically, the conformational equilibrium of the kinase
      is shifted by 13.2 kcal mol-1 to favor the active conformation after A-loop
      phosphorylation, which increases substrate binding affinity of the activated
      kinase. This free energy shift is achieved primarily via destabilization of the
      inactive conformation. The free energy of the catalytic reaction is also changed
      by 3.3 kcal mol-1 after the phosphorylation and in the end, facilitates product
      release. Analyses of MD simulations showed that A-loop phosphorylation produces
      these energetic effects by perturbing the side chain interactions around each A
      loop tyrosine. These interaction changes are propagated to the remainder of the
      kinase to modify the orientations and dynamics of the alphaC-helix and A-loop,
      and together yield the observed free energy changes. Since many protein kinases
      share similar interactions identified in this work, the mechanisms of kinase
      allostery and catalysis unraveled here can be applicable to them.

PMID- 28507718
TI  - Copper-catalyzed direct alkylation of heteroarenes.
AB  - An efficient and broadly applicable process is reported for the direct alkylation
      of C-H bonds in heteroarenes, privileged scaffolds in many areas of science. This
      reaction is based on the copper-catalyzed addition of alkyl radicals generated
      from activated secondary and tertiary alkyl bromides to a wide range of arenes,
      including furans, thiophenes, pyrroles, and their benzo-fused derivatives, as
      well as coumarins and quinolinones.

PMID- 28507719
TI  - Broad substrate tolerance of tubulin tyrosine ligase enables one-step site
      specific enzymatic protein labeling.
AB  - The broad substrate tolerance of tubulin tyrosine ligase is the basic rationale
      behind its wide applicability for chemoenzymatic protein functionalization. In
      this context, we report that the wild-type enzyme enables ligation of various
      unnatural amino acids that are substantially bigger than and structurally
      unrelated to the natural substrate, tyrosine, without the need for extensive
      protein engineering. This unusual substrate flexibility is due to the fact that
      the enzyme's catalytic pocket forms an extended cavity during ligation, as
      confirmed by docking experiments and all-atom molecular dynamics simulations.
      This feature enabled one-step C-terminal biotinylation and fluorescent coumarin
      labeling of various functional proteins as demonstrated with ubiquitin, an
      antigen binding nanobody, and the apoptosis marker Annexin V. Its broad substrate
      tolerance establishes tubulin tyrosine ligase as a powerful tool for in vitro
      enzyme-mediated protein modification with single functional amino acids in a
      specific structural context.

PMID- 28507720
TI  - In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury
      and liver cancer via a near-infrared fluorescent probe.
AB  - The liver, a main detoxification organ, has evolved a complex enzymatic system to
      respond to multiple pathological conditions, in which leucine aminopeptidase
      (LAP) has been reported to participate in detoxifying cisplatin in hepatoma cells
      and contribute to the intrinsic drug resistance. In vivo imaging of LAP activity
      in liver disease models is thus helpful to further understand the function of LAP
      in detoxification and medicine, but such an imaging approach is still lacking.
      Herein, we develop a selective and sensitive near-infrared fluorescent probe
      (HCAL) for this purpose. Using the probe, combined with confocal fluorescence
      imaging, we disclose the upregulations of LAP in acetaminophen-induced liver
      injury and tumor-bearing mice models. Supplementary acetylcysteine can suppress
      this upregulation, revealing that the LAP increase may be connected with a
      deficiency in biothiols. Moreover, HCAL has been used to image LAP in hepatoma
      cells, tumor tissues and xenograft tumor mice models successfully. These results
      demonstrate that HCAL may be a promising tool for studying the function of LAP in
      LAP-associated liver diseases.

PMID- 28507721
TI  - Mo6+ activated multimetal oxygen-evolving catalysts.
AB  - Water splitting is key to electrically-powered chemical fuel synthesis, but the
      slow kinetics of the oxygen evolution reaction (OER) hinder the wider promotion
      of such technology. Several first-row (3d) transition metal-based catalysts have
      been developed for the OER; however, these catalysts still require operating
      voltages that lie well above the fundamental thermodynamic potential. Here, we
      report high-valence metal molybdenum (Mo6+) modulated 3d metal (oxy)hydroxides.
      The obtained multimetal FeCoMo based OER catalysts require an overpotential of
      277 mV to reach the current density of 10 mA cm-2 on the glassy carbon electrode,
      and there was no evidence of degradation for about 40 hours of stability testing.
      The catalysts stay in their amorphous phases, potentially with atomically
      homogenous metal distribution. The in situ X-ray adsorption analysis
      unambiguously reveals the tuned electronic structures of the 3d metals owing to
      Mo6+, further demonstrating the modification effect of a high-valence metal for
      designing highly-efficient OER catalysts.

PMID- 28507722
TI  - Novel bright-emission small-molecule NIR-II fluorophores for in vivo tumor
      imaging and image-guided surgery.
AB  - Though high brightness and biocompatible small NIR-II dyes are highly desirable
      in clinical or translational cancer research, their fluorescent cores are
      relatively limited and their synthetic processes are somewhat complicated.
      Herein, we have explored the design and synthesis of novel NIR-II fluorescent
      materials (H1) without tedious chromatographic isolation with improved
      fluorescence performance (QY ~ 2%) by introducing 2-amino 9,9-dialkyl-substituted
      fluorene as a donor into the backbone. Several types of water-soluble and
      biocompatible NIR-II probes: SXH, SDH, and H1 NPs were constructed via different
      chemical strategies based on H1, and then their potential to be used in in vivo
      tumor imaging and image-guided surgery in the NIR-II region was explored. High
      levels of uptake were obtained for both passive and active tumor targeting probes
      SXH and SDH. Furthermore, high resolution imaging of blood vessels on tumors and
      the whole body of living mice using H1 NPs for the first time has demonstrated
      precise NIR-II image-guided sentinel lymph node (SLN) surgery.

PMID- 28507723
TI  - p-Doping of graphene in hybrid materials with 3,10-diazapicenium dications.
AB  - N,N'-Didodecyl-substituted 3,10-diazapicenium salts featuring bromide and
      hexafluorophosphate counterions have been designed as novel dopants to realize
      individualized graphene sheets in a series of cutting edge experiments and to
      intrinsically stabilize them via p-doping. Importantly, electrochemical studies
      revealed two consecutive irreversible one-electron reductions of the N,N'
      didodecyl-substituted 3,10-diazapicenium salts to yield the corresponding radical
      cation and neutral quinoidal species. Formation of both species was accompanied
      by characteristic changes in the absorption spectra. The 3,10-diazapicenium
      bromide was found to be a potent dopant to produce hybrid materials with
      exfoliated graphene. Microscopy based on AFM and TEM imaging and spectroscopy
      based on Raman probing corroborated that, upon drying, the hybrid material
      consists of few layer (5-8 layers) turbostratic graphene sheets that are p-doped.
      Our findings identify the newly synthesized N,N'-dialkylated 3,10-diazapicenium
      salts as highly promising candidates for the fabrication of functional graphene
      materials with tailored properties.

PMID- 28507724
TI  - Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of
      cancer.
AB  - Visual inspection of tumour tissues does not reveal the complex metabolic changes
      that differentiate cancer and its sub-types from healthy tissues. Mass
      spectrometry imaging, which quantifies the underlying chemistry, represents a
      powerful tool for the molecular exploration of tumour tissues. A 3-dimensional
      topological description of the chemical properties of the tumour permits the
      formulation of hypotheses about the biological composition and interactions and
      the possible causes of its heterogeneous structure. The large amount of
      information contained in such datasets requires powerful tools for its analysis,
      visualisation and interpretation. Linear methods for unsupervised dimensionality
      reduction, such as PCA, are inadequate to capture the complex non-linear
      relationships present in these data. For this reason, a deep unsupervised neural
      network based technique, parametric t-SNE, is adopted to map a 3D-DESI-MS dataset
      from a human colorectal adenocarcinoma biopsy onto a 2-dimensional manifold. This
      technique allows the identification of clusters not visible with linear methods.
      The unsupervised clustering of the tumour tissue results in the identification of
      sub-regions characterised by the abundance of identified metabolites, making
      possible the formulation of hypotheses to account for their significance and the
      underlying biological heterogeneity in the tumour.

PMID- 28507725
TI  - Metal-free C-H alkylation of heteroarenes with alkyltrifluoroborates: a general
      protocol for 1 degrees , 2 degrees  and 3 degrees  alkylation.
AB  - A photoredox-catalyzed C-H functionalization of heteroarenes using a variety of
      primary, secondary, and tertiary alkyltrifluoroborates is reported. Using
      Fukuzumi's organophotocatalyst and a mild oxidant, conditions amenable for
      functionalizing complex heteroaromatics are described, providing a valuable tool
      for late-stage derivatization. The reported method addresses the three major
      limitations of previously reported photoredox-mediated Minisci reactions: (1) use
      of superstoichiometric amounts of a radical precursor, (2) capricious
      regioselectivity, and (3) incorporation of expensive photocatalysts.
      Additionally, a number of unprecedented, complex alkyl radicals are used, thereby
      increasing the chemical space accessible to Minisci chemistry. To showcase the
      application in late-stage functionalization, quinine and camptothecin analogues
      were synthesized. Finally, NMR studies were conducted to provide a
      rationalization for the heteroaryl activation that permits the use of a single
      equivalent of radical precursor and also leads to enhanced regioselectivity.
      Thus, by 1H and 13C NMR a distinct heteroaryl species was observed in the
      presence of acid catalyst and BF3.

PMID- 28507727
TI  - Correlation between hemoglobin A1c and serum lipid profile in Afghani patients
      with type 2 diabetes: hemoglobin A1c prognosticates dyslipidemia.
AB  - BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased prevalence of
      dyslipidemia, which contributes to their high risk of cardiovascular diseases
      (CVDs). This study is an attempt to determine the correlation between hemoglobin
      A1c (HbA1c) and serum lipid profile and to evaluate the importance of HbA1c as an
      indicator of dyslipidemia in Afghani patients with T2DM. METHODS: A total of 401
      Afghani patients with T2DM (men, 175; women, 226; mean age, 51.29 years) were
      included in this study. The whole blood and sera were analyzed for fasting blood
      sugar (FBS), HbA1c, total cholesterol (TC), triglycerides (TGs), high-density
      lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).
      Dyslipidemia was defined according to the National Cholesterol Education Program
      Adult Treatment Panel III (NCEP ATP III) guidelines. Diabetes was defined as per
      American Diabetes Association criteria. The correlation of FBS, HbA1c with lipid
      ratios and individual lipid indexes were analyzed. The statistical analysis was
      done by SPSS statistical package version 16.0. RESULTS: The mean age +/- standard
      deviation of male and female patients were 51.71 +/- 11.70 and 50.97 +/- 10.23
      years respectively. There was a significant positive correlation between HbA1c,
      TC, TG, LDL-C and LDL-C/HDL-C ratio. The correlation between HbA1c and HDL-C was
      negative and was statistically nonsignificant. Furthermore, HbA1c was found to be
      a predictor of hypercholesterolemia, LDL-C and TG via a linear regression
      analysis. Patients with HbA1c value greater than 7.0% had significantly higher
      value of cholesterol, LDL-C, and LDL-C/HDL-C ratio compared with patients with an
      HbA1c value up to 7.0%. CONCLUSIONS: Apart from a reliable glycemic index, HbA1c
      can also be used as a predictor of dyslipidemia and thus early diagnosis of
      dyslipidemia can be used as a preventive measure for the development of CVD in
      patients with T2DM.

PMID- 28507726
TI  - Adapting tissue-engineered in vitro CNS models for high-throughput study of
      neurodegeneration.
AB  - Neurodegenerative conditions remain difficult to treat, with the continuing
      failure to see therapeutic research successfully advance to clinical trials. One
      of the obstacles that must be overcome is to develop enhanced models of disease.
      Tissue engineering techniques enable us to create organised artificial central
      nervous system tissue that has the potential to improve the drug development
      process. This study presents a replicable model of neurodegenerative pathology
      through the use of engineered neural tissue co-cultures that can incorporate
      cells from various sources and allow degeneration and protection of neurons to be
      observed easily and measured, following exposure to neurotoxic compounds -
      okadaic acid and 1-methyl-4-phenylpyridinium. Furthermore, the technology has
      been miniaturised through development of a mould with 6 mm length that recreates
      the advantageous features of engineered neural tissue co-cultures at a scale
      suitable for commercial research and development. Integration of human-derived
      induced pluripotent stem cells aids more accurate modelling of human diseases,
      creating new possibilities for engineered neural tissue co-cultures and their use
      in drug screening.

PMID- 28507728
TI  - Therapeutic plasmapheresis for hypertriglyceridemia-associated acute
      pancreatitis: case series and review of the literature.
AB  - BACKGROUND: Severe hypertriglyceridemia (HTG) is the third leading cause of acute
      pancreatitis (AP) in the United States. The current standard of care includes
      management of HTG using pharmacological therapy. More recently, plasmapheresis
      has been proposed as a therapeutic tool for decreasing triglyceride (TG) levels,
      especially in critically ill patients. Few studies are available to ascertain
      overall benefits of plasmapheresis over traditional management. OBJECTIVE: To
      analyze the outcomes of patients treated with plasmapheresis for severe HTG
      associated pancreatitis. METHODS: We conducted a retrospective chart review of
      three patients with severe HTG- associated (TGs greater than 1000 mg/dl; 11.29
      mmol/l) AP at the Methodist University Hospital. All the patients underwent
      plasmapheresis as part of their treatment. RESULTS: The average TG level before
      plasmapheresis was 3532 mg/dl (range: 2524-4562 mg/dl; 39.9 mmol/l; range: 28.5
      51.6 mmol/l). All patients made a full recovery, with a significant improvement
      in TG levels after plasmapheresis. The mean number of sessions was 1.3 (range 1
      2), and mean TG level after plasmapheresis was 1051 mg/dl (range: 509-1771 mg/dl;
      11.9 mmol/l; range: 5.8-20 mmol/l). After the first session, the average
      reduction of TG level was 2481 mg/dl (range 753-3750 mg/dl; 28 mmol/l; range: 8.5
      42.4 mmol/l) or approximately 70%. None of the patients developed complications
      related to plasmapheresis. CONCLUSIONS: Plasmapheresis can be an effective and
      rapid treatment option in patients with severe HTG and complications. However,
      further research, including randomized controlled studies, is necessary.

PMID- 28507729
TI  - Difference in clinical presentation between women and men in incident primary
      Sjogren's syndrome.
AB  - BACKGROUND: A more severe disease phenotype has been reported in men compared to
      women in several rheumatic diseases. However, studies have not conclusively
      established sex-related clinical features in primary Sjogren's syndrome (pSS). In
      this study, we therefore investigated the clinical presentation of pSS in women
      and men at diagnosis. METHODS: Incident, treatment naive patients (n = 199)
      during a 5-year period in a specified area were prospectively included and
      examined for items of classification criteria for pSS as well as extraglandular
      manifestations (EGM). Serum was sampled at the time of diagnosis and anti
      Ro52/SSA levels were measured by ELISA. Replication of significant findings was
      confirmed in an independent cohort of pSS patients (n = 377), and meta-analysis
      was performed. RESULTS: An increased frequency of extraglandular manifestations
      in men was observed and replicated (p = 0.05, p = 0.0003, and pmeta = 0.002).
      This related to pulmonary involvement, vasculitis, and lymphadenopathy being more
      common in men, for whom a lower age at diagnosis was observed in the exploratory
      cohort. Additionally, SSA-positive male patients had significantly higher levels
      of anti-Ro52 levels than their female counterparts in sera available for analysis
      (p = 0.02). CONCLUSIONS: Our analysis of two independent cohorts of incident pSS
      demonstrates that the presence and number of EGM are significantly more frequent
      among men with pSS than women at diagnosis. Importantly, around half of the male
      patients presented with more than one EGM at diagnosis, supporting the conclusion
      that pSS in men represents a more severe form of disease, regardless of the lower
      risk for men to develop pSS.

PMID- 28507732
TI  - Conquering the deadly stroke: Perspective on a surgeon's odyssey.
AB  - *An odyssey of a Japanese surgeon, who survived a life-threatening hemorrhagic
      stroke.*Self-motivation and adherence to work ethics displayed by the surgeon to
      return to work is admirable.*Passion is a detrimental factor that enables
      surgeons to overcome a roadblock to their career.

PMID- 28507731
TI  - Patient engagement with surgical site infection prevention: an expert panel
      perspective.
AB  - Despite remarkable developments in the use of surgical techniques, ergonomic
      advancements in the operating room, and implementation of bundles, surgical site
      infections (SSIs) remain a substantial burden, associated with increased
      morbidity, mortality and healthcare costs. National and international
      recommendations to prevent SSIs have been published, including recent guidelines
      by the World Health Organization, but implementation into clinical practice
      remains an unresolved issue. SSI improvement programs require an integrative
      approach with measures taken during the pre-, intra- and postoperative care from
      the numerous stakeholders involved. The current SSI prevention strategies have
      focused mainly on the role of healthcare workers (HCWs) and procedure related
      risk factors. The importance and influence of patient participation is becoming
      an increasingly important concept and advocated as a means to improve patient
      safety. Novel interventions supporting an active participative role within SSI
      prevention programs have not been assessed. Empowering patients with information
      they require to engage in the process of SSI prevention could play a major role
      for the implementation of recommendations. Based on available scientific
      evidence, a panel of experts evaluated options for patient involvement in order
      to provide pragmatic recommendations for pre-, intra- and postoperative
      activities for the prevention of SSIs. Recommendations were based on existing
      guidelines and expert opinion. As a result, 9 recommendations for the surgical
      patient are presented here, including a practice brief in the form of a patient
      information leaflet. HCWs can use this information to educate patients and allow
      patient engagement.

PMID- 28507733
TI  - Assessment of postgraduate skin lesion education among Iowa family physicians.
AB  - BACKGROUND: Family medicine physicians play a pivotal role in the prevention and
      early detection of skin cancer. Our objective was to evaluate how family
      physicians believe their postgraduate training in skin cancer screening and
      prevention has prepared them for independent practice and to assess the need for
      enhanced skin lesion teaching in a family medicine residency setting. METHODS: A
      descriptive, cross-sectional survey investigating provider demographics,
      confidence in providing dermatological care, residency training, current medical
      practice, and skin cancer prevention beliefs was mailed to all family medicine
      physicians in the state of Iowa as listed in the Iowa Academy of Family
      Physicians annual directory in 2006 (N = 1069). RESULTS: A total of 575 family
      medicine physicians completed the survey for an overall response rate of 53.8%.
      Overall, family medicine physicians reported feeling confident in their ability
      to diagnose skin lesions (83.2%), differentiate between benign and malignant
      lesions (85.3%), and perform a biopsy of a lesion (94.3%). Only 65% of surveyed
      physicians felt that their residency program adequately trained them in
      diagnosing skin lesions and 65.7% of physicians agree that they could have
      benefited from additional training on skin lesions during residency training.
      Nearly 90% of clinicians surveyed believe that skin cancer screenings are the
      standard of care; however, only 51.8% perform skin cancer screening examinations
      during adult health maintenance visits more than 75% of the time. The primary
      reason listed by respondents who said they do not routinely perform skin cancer
      screenings was inadequate time (68.2%). CONCLUSION: Family medicine physicians in
      the state of Iowa are confident in evaluating skin lesions. However, they
      reported a need for additional enhanced, targeted skin lesion education in family
      medicine residency training programs. Physicians believe that skin cancer
      screening examination is the standard of care, but find that inadequate time
      increasingly hinders skin cancer screening during routine health maintenance
      examinations.

PMID- 28507734
TI  - Adverse effect profile comparison of pain regimens with and without intravenous
      acetaminophen in total hip and knee arthroplasty patients.
AB  - BACKGROUND: The use of adjunct, non-opioid agents is integral for pain control
      following total hip and knee arthroplasty. Literature comparing safety profiles
      of intravenous acetaminophen versus opioids is lacking. OBJECTIVE: To determine
      whether there is a difference in frequency and type of adverse effects between
      intravenous acetaminophen-treated and non-intravenous acetaminophen-treated
      patients. Primary safety endpoints included any adverse effect noted in the
      electronic medical record post-surgically. Secondary endpoints included changes
      in laboratory values, vital signs, and pain scores. METHODS: This is a
      retrospective, matched, cohort study with data collected from electronic medical
      records. Adverse effects were collected from progress notes, nursing notes, and
      post-operative notes. Mean pain score was measured by the 11-point visual analog
      scale over a 72-h period. RESULTS: A total of 609 patients who underwent a total
      hip or knee replacement were included. In all, 406 patients were treated with
      intravenous acetaminophen, and 203 patients received medication management
      without intravenous acetaminophen. More patients treated with intravenous
      acetaminophen experienced an adverse effect compared to patients who did not
      receive intravenous acetaminophen (91.63% versus 84.73%; p = 0.012). Mean
      cumulative acetaminophen exposure was similar in the intravenous acetaminophen
      group (7704.89 +/- 2558.6 versus 7260.1 +/- 3016.09 mg; p = 0.07). Mean opioid
      use was similar in the intravenous acetaminophen group as compared to the non
      intravenous acetaminophen group (209.61 +/- 555.09 versus 163.89 +/- 232.44 mg; p
      = 0.152). Significantly higher mean pain scores were found in the intravenous
      acetaminophen group during the 72-h post-surgery period as compared with non
      intravenous acetaminophen-treated patients. CONCLUSION: The increased utilization
      of intravenous acetaminophen in multimodal pain management did not result in an
      improved safety or tolerability profile or reduced opioid utilization in
      orthopedic patients.

PMID- 28507730
TI  - Application of the adverse outcome pathway (AOP) concept to structure the
      available in vivo and in vitro mechanistic data for allergic sensitization to
      food proteins.
AB  - BACKGROUND: The introduction of whole new foods in a population may lead to
      sensitization and food allergy. This constitutes a potential public health
      problem and a challenge to risk assessors and managers as the existing
      understanding of the pathophysiological processes and the currently available
      biological tools for prediction of the risk for food allergy development and the
      severity of the reaction are not sufficient. There is a substantial body of in
      vivo and in vitro data describing molecular and cellular events potentially
      involved in food sensitization. However, these events have not been organized in
      a sequence of related events that is plausible to result in sensitization, and
      useful to challenge current hypotheses. The aim of this manuscript was to collect
      and structure the current mechanistic understanding of sensitization induction to
      food proteins by applying the concept of adverse outcome pathway (AOP). MAIN
      BODY: The proposed AOP for food sensitization is based on information on
      molecular and cellular mechanisms and pathways evidenced to be involved in
      sensitization by food and food proteins and uses the AOPs for chemical skin
      sensitization and respiratory sensitization induction as templates. Available
      mechanistic data on protein respiratory sensitization were included to fill out
      gaps in the understanding of how proteins may affect cells, cell-cell
      interactions and tissue homeostasis. Analysis revealed several key events (KE)
      and biomarkers that may have potential use in testing and assessment of proteins
      for their sensitizing potential. CONCLUSION: The application of the AOP concept
      to structure mechanistic in vivo and in vitro knowledge has made it possible to
      identify a number of methods, each addressing a specific KE, that provide
      information about the food allergenic potential of new proteins. When applied in
      the context of an integrated strategy these methods may reduce, if not replace,
      current animal testing approaches. The proposed AOP will be shared at the
      www.aopwiki.org platform to expand the mechanistic data, improve the confidence
      in each of the proposed KE and key event relations (KERs), and allow for the
      identification of new, or refinement of established KE and KERs.

PMID- 28507736
TI  - Mark E Josephson The Elegance of Genius. . .

PMID- 28507737
TI  - Mark E Josephson: Characteristics of Leadership.
AB  - Mark Josephson is without a doubt the most fascinating person I have ever met. I
      am proud to have had a close friendship with him and I miss him immensely. I have
      written in the past about his amazing academic contributions, but in a way I am
      relieved that this is not my topic today. I will instead talk about the unique
      aspects of his personality that allowed him to be a great leader in the field of
      electrophysiology and a powerful influence on the personal development of those
      of us who had the great good fortune of interacting with him closely.

PMID- 28507739
TI  - "What Would He Do Next?"

PMID- 28507740
TI  - Mark Josephson: Pioneer, Educator and Mentor to a Generation of Cardiac
      Electrophysiologists.
AB  - In January 2017 we lost a giant in cardiac electrophysiology, whose work and
      teachings touched all of us working in the field. Mark Josephson's early work,
      building on the work of Hein Wellens in using programmed stimulation and catheter
      mapping to understand scar-related ventricular tachycardias, led the way to
      surgical and then catheter ablation as a viable therapy for that arrhythmia. His
      seminal observations are many and catalogued in 'The Josephson School' a
      wonderful book with 59 Chapters and extensive commentary devoted to his
      research.1 In the area of scar-related VT alone his work characterising
      electrograms in infarct scars and defining their relation to reentry circuits led
      to the development of substrate mapping techniques in common use today. His
      attention to the details of recording techniques helped establish the standards
      for electrophysiology studies. His investigational studies are not limited to
      ventricular arrhythmias but extend across the spectrum of cardiac
      electrophysiology. He was a superb observer with a talent for recognising subtle,
      unexpected events and delving deep to explore their potential mechanisms and
      significance.

PMID- 28507735
TI  - Does dysfunction of the autonomic nervous system affect success of renal
      denervation in reducing blood pressure?
AB  - OBJECTIVES: Renal denervation is an interventional approach aiming to reduce high
      blood pressure. Its efficacy is subject of controversial debate. We analyzed
      autonomic function in patients undergoing renal denervation to identify
      responders. METHODS: A total of 21 patients with treatment-resistant hypertension
      scheduled for renal denervation were included. Heart rate variability, pupillary
      function and sympathetic skin response were examined prior to intervention.
      Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure
      readings were taken. RESULTS: Patients were stratified according to sympathetic
      nervous system function. Sympathetic activity was reduced in 12 participants
      (group 1) and normal or enhanced in nine patients (group 2). The mean of daytime
      systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95%
      confidence interval for difference, 1-21 mmHg, p = 0.035) and from 166 to 145
      mmHg (8-34 mmHg, p = 0.005), respectively. In a linear model, blood pressure
      reduction was 11.3 mmHg (0.3-22 mmHg) greater in group 2 than in group 1 (p =
      0.045). CONCLUSION: Patients with preexisting reduced activity of the sympathetic
      nervous system benefited less from renal denervation.

PMID- 28507738
TI  - Mark E Josephson: Clinical Investigator.
AB  - Mark E Josephson entered the world of clinical cardiac electrophysiology (EP)
      almost at its inception (1972); with so much to learn and so many directions one
      could take, he dived into the field with unbridled enthusiasm and an uncommon -
      perhaps almost unique - aptitude for asking questions and finding ways to answer
      them. Few aspects of EP escaped his indelible influence. In this short paper, I
      will attempt to touch on some of the high points of his astounding career as a
      clinical investigator.

PMID- 28507741
TI  - Mark Josephson and the ICD: A Personal Perspective.
AB  - Mark Josephson dedicated his career to the prevention of premature sudden cardiac
      death (SCD). Toward that goal, he was an early adopter of the implantable
      cardioverter defibrillator (ICD) and indefatigable advocate for better ICD
      technology,[1] both as a clinical tool and as living laboratory to study SCD in
      ambulatory patients. With characteristic intellectual integrity and analytical
      rigour, he sought an honest and balanced appraisal of the life-saving benefits
      and serious complications of this unique therapy.

PMID- 28507742
TI  - Mark E Josephson: The Boston Years.
AB  - Mark Josephson came to Beth Israel Hospital from the University of Pennsylvania
      in 1992, having firmly established a reputation as a master clinician, scientist
      and educator. He had built one of the premier electrophysiology (EP) services in
      the world in Pennsylvania and had become Chief of Cardiology there by the age of
      35. In those days, Beth Israel was well known for its interventional cardiology
      and cardiac imaging but had not yet committed to the development of a modern EP
      section. The buzz surrounding Mark's arrival predicted an outspoken, larger than
      life and irreverent character who would profoundly change the place.

PMID- 28507744
TI  - Mahaim Accessory Pathways.
AB  - The term Mahaim conduction is conventionally used to describe decrementally
      conducting connections between the right atrium or the AV node and the right
      ventricle in or close to the right bundle branch. Although such pathways are
      rare, their unique properties make their diagnosis and treatment cumbersome. In
      this article we review the published evidence, and discuss the
      electrocardiographic and electrophysiological characteristics as well as the
      anatomy and origin of these fibres.

PMID- 28507743
TI  - Electrophysiological Testing for the Investigation of Bradycardias.
AB  - In this article we review the role of electrophysiological testing in patients
      presenting with bradycardia due to sinus node or atrioventricular node disease.
      In sinus bradycardia the role of electrophysiology studies is not established. In
      AV conduction disturbances, an electrophysiology study may be necessary both for
      the establishment of atrioventricular block as the main cause of symptoms, and
      for identification of the anatomic site of block that may dictate the potential
      need of permanent pacing.

PMID- 28507747
TI  - The clinical and cost implications of failed endoscopic hemostasis in
      gastroduodenal ulcer bleeding.
AB  - AIM: The aim of this article is to evaluate the clinical and cost implications of
      failed endoscopic hemostasis in patients with gastroduodenal ulcer bleeding.
      METHODS: A retrospective claims analysis of the Medicare Provider Analysis and
      Review (MedPAR) file was conducted to identify all hospitalizations for
      gastroduodenal ulcer bleeding in the year 2012. The main outcome measures were to
      compare all-cause mortality, total length of hospital stay (LOS), hospital costs
      and payment between patients managed with one upper gastrointestinal (UGI)
      endoscopy versus more than one UGI endoscopy or requiring interventional
      radiology-guided hemostasis (IRH) or surgery after failed endoscopic attempt.
      RESULTS: The MedPAR claims data evaluated 13,501 hospitalizations, of which
      12,242 (90.6%) reported one UGI endoscopy, 817 (6.05%) reported >1 UGI endoscopy,
      303 (2.24%) reported IRH after failed endoscopy and 139 (1.03%) reported
      surgeries after failed endoscopy. All cause-mortality was significantly lower for
      patients who underwent only one UGI endoscopy (3%) compared to patients requiring
      >1 endoscopy (6%), IRH (9%) or surgery (14%), p < 0.0001. The median LOS was
      significantly lower for patients who underwent only one UGI endoscopy (four days)
      compared to patients requiring >1 endoscopy (eight days), IRH (nine days) or
      surgery (15 days), p < 0.0001. The median hospital costs were significantly lower
      for patients who underwent one UGI endoscopy ($10,518) compared to patients
      requiring >1 endoscopy ($20,055), IRH ($34,730) or surgery ($47,589), p < 0.0001.
      CONCLUSIONS: Failure to achieve hemostasis at the index endoscopy has significant
      clinical and cost implications. When feasible, a repeat endoscopy must be
      attempted followed by IRH. Surgery should preferably be reserved as a last resort
      for patients who fail other treatment measures.

PMID- 28507746
TI  - Guidelines on eosinophilic esophagitis: evidence-based statements and
      recommendations for diagnosis and management in children and adults.
AB  - INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent
      esophageal diseases and the leading cause of dysphagia and food impaction in
      children and young adults. This underlines the importance of optimizing diagnosys
      and treatment of the condition, especially after the increasing amount of
      knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and
      EUREOS deemed it necessary to update the current guidelines regarding conceptual
      and epidemiological aspects, diagnosis, and treatment of EoE. METHODS: General
      methodology according to the Appraisal of Guidelines for Research and Evaluation
      (AGREE) II and the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) system was used in order to comply with current standards of
      evidence assessment in formulation of recommendations. An extensive literature
      search was conducted up to August 2015 and periodically updated. The working
      group consisted of gastroenterologists, allergists, pediatricians,
      otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based
      reviews were performed based upon relevant clinical questions with respect to
      patient-important outcomes. RESULTS: The guidelines include updated concept of
      EoE, evaluated information on disease epidemiology, risk factors, associated
      conditions, and natural history of EoE in children and adults. Diagnostic
      conditions and criteria, the yield of diagnostic and disease monitoring
      procedures, and evidence-based statements and recommendation on the utility of
      the several treatment options for patients EoE are provided. Recommendations on
      how to choose and implement treatment and long-term management are provided based
      on expert opinion and best clinical practice. CONCLUSION: Evidence-based
      recommendations for EoE diagnosis, treatment modalities, and patients' follow up
      are proposed in the guideline.

PMID- 28507745
TI  - Performance measures for lower gastrointestinal endoscopy: a European Society of
      Gastrointestinal Endoscopy (ESGE) quality improvement initiative.
AB  - The European Society of Gastrointestinal Endoscopy and United European
      Gastroenterology present a short list of key performance measures for lower
      gastrointestinal endoscopy. We recommend that endoscopy services across Europe
      adopt the following seven key performance measures for lower gastrointestinal
      endoscopy for measurement and evaluation in daily practice at a center and
      endoscopist level: 1 rate of adequate bowel preparation (minimum standard 90%); 2
      cecal intubation rate (minimum standard 90%); 3 adenoma detection rate (minimum
      standard 25%); 4 appropriate polypectomy technique (minimum standard 80%); 5
      complication rate (minimum standard not set); 6 patient experience (minimum
      standard not set); 7 appropriate post-polypectomy surveillance recommendations
      (minimum standard not set). Other identified performance measures have been
      listed as less relevant based on an assessment of their importance, scientific
      acceptability, feasibility, usability, and comparison to competing measures.

PMID- 28507749
TI  - Splenic volume differentiates complicated and non-complicated celiac disease.
AB  - BACKGROUND: Studies in small groups of patients indicated that splenic volume
      (SV) may be decreased in patients with celiac disease (CD), refractory CD (RCD)
      type II and enteropathy-associated T-cell lymphoma (EATL). OBJECTIVE: The
      objective of this article is to evaluate SV in a large cohort of uncomplicated
      CD, RCD II and EATL patients and healthy controls. METHODS: The retrospective
      cohort consisted of 77 uncomplicated CD (of whom 39 in remission), 29 RCD II, 24
      EATL and 12 patients with both RCD II and EATL. The control group included 149
      healthy living kidney donors. SV was determined on computed tomography. RESULTS:
      The median SV in the uncomplicated CD group was significantly larger than in
      controls (202 cm3 (interquartile range (IQR): 154-275) versus 183 cm3 (IQR: 140
      232), p = 0.02). After correction for body surface area, age and gender, the
      ratio of SV in uncomplicated CD versus controls was 1.28 (95% confidence
      interval: 1.20-1.36; p < 0.001). The median SV in RCD II patients (118 cm3 (IQR
      83-181)) was smaller than the median SV in the control group (p < 0.001).
      CONCLUSION: This study demonstrates large inter-individual variation in SV. SV is
      enlarged in uncomplicated CD. The small SV in RCD II may be of clinical relevance
      considering the immune-compromised status of these patients.

PMID- 28507748
TI  - Comparison of the pull and introducer percutaneous endoscopic gastrostomy
      techniques in patients with head and neck cancer.
AB  - BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) in head and
      neck cancer (HNC) patients is associated with higher complication and mortality
      rates when compared to a general patient population. The pull technique is still
      the preferred technique worldwide but it has some limitations. The aim of this
      study is to compare the pull and introducer PEG techniques in patients with HNC.
      PATIENTS AND METHODS: This study is based on a retrospective analysis of a
      prospectively collected database of 309 patients with HNC who underwent PEG in
      the Cancer Institute of Sao Paulo. RESULTS: The procedure was performed with the
      standard endoscope in 205 patients and the introducer technique was used in 137
      patients. There was one procedure-related mortality. Age, sex and albumin level
      were similar in both groups. However in the introducer technique group, patients
      had a higher tumor stage, a lower Karnofsky status, and presented more frequently
      with tracheostomy and trismus. Overall, major, minor, immediate and late
      complications and 30-day mortality rates were similar but the introducer
      technique group presented more minor bleeding and tube dysfunctions. CONCLUSION:
      The push and introducer PEG techniques seem to be both safe and effective but
      present different complication profiles. The choice of PEG technique in patients
      with HNC should be made individually.

PMID- 28507750
TI  - Effects of conventional and a novel colonic-release bile acid sequestrant, A3384,
      on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and
      patients with bile acid diarrhoea.
AB  - BACKGROUND: Primary bile acid diarrhoea (BAD) is associated with increased bile
      acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid
      sequestrants are used as therapy, but are poorly tolerated and may exacerbate
      FGF19 deficiency. AIM: The purpose of this study was to evaluate the
      pharmacological effects of conventional sequestrants and a colonic-release
      formulation preparation of colestyramine (A3384) on bile acid metabolism and
      bowel function in patients with BAD. METHODS: Patients with seven-day 75selenium
      homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double
      blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g
      (n = 7) or placebo (n = 6). Thirteen patients were taking conventional
      sequestrants at the start of the study. Symptoms were recorded and serum FGF19
      and 7alpha-hydroxy-4-cholesten-3-one (C4) measured. RESULTS: Median serum FGF19
      on conventional sequestrant treatment was 28% lower than baseline values in BAD
      (p < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p <
      0.001). No changes were seen on starting or withdrawing A3384. A3384 improved
      diarrhoeal symptoms, with a median reduction of 2.2 points on a 0-10 Likert scale
      compared to placebo, p < 0.05. CONCLUSIONS: Serum FGF19 was suppressed and bile
      acid production up-regulated on conventional bile acid sequestrants, but not with
      A3384. This colonic-release formulation of colestyramine produced symptomatic
      benefit in patients with BAD.

PMID- 28507752
TI  - Effective treatment of benign biliary strictures with a removable, fully covered,
      self-expandable metal stent: A prospective, multicenter European study.
AB  - BACKGROUND: Temporary placement of removable, fully covered, self-expandable
      metal stents (fcSEMS) for treatment of benign biliary strictures (BBS) has been
      reported to be effective. However, the optimal extraction time point remains
      unclear and stent migration has been a major concern. OBJECTIVE: The objective of
      this study was to evaluate the efficacy and safety of this treatment modality
      using an fcSEMS with a special antimigration design and prolonged stent indwell
      time. METHODS: We performed a prospective, single-arm study at six tertiary care
      centers in Europe. Patients with BBS underwent endoscopic or percutaneous
      implantation of an fcSEMS (GORE(r) VIABIL(r) Biliary Endoprosthesis, W.L. Gore &
      Associates, Flagstaff, AZ, USA). The devices were scheduled to be removed nine
      months later, and patients were to return for follow-up for an additional 15
      months. RESULTS: Forty-three patients were enrolled in the study. Stricture
      etiology was chronic pancreatitis in the majority of patients (57.5%). All fcSEMS
      were placed successfully, either endoscopically (76.7%) or percutaneously
      (23.3%). Stent migration was observed in two patients (5.2%). Primary patency of
      the SEMS prior to removal was 73.0%. All attempted stent removals were
      successful. At removal, stricture was resolved or significantly improved without
      need for further therapy in 78.9% of patients. Stricture recurrence during a
      follow-up of two years post-implant was observed in two patients. CONCLUSIONS:
      Temporary placement of the fcSEMS is a feasible, safe and effective treatment for
      BBS. The design of the device used in this study accounts for very low migration
      rates and facilitates easy stent retrieval, even after it has been in place for
      up to 11 months.

PMID- 28507753
TI  - Yield of magnetic resonance cholangiopancreatography for the investigation of
      bile duct dilatation in asymptomatic patients.
AB  - BACKGROUND: Biliary dilatation in the asymptomatic patient is a frequent
      incidental finding in the work-up for which there are no current guidelines.
      OBJECTIVES: The purpose of this study was to determine the yield of magnetic
      resonance cholangiopancreatography (MRCP) in asymptomatic patients with an
      incidental finding of biliary duct dilatation. METHODS: The study included 68
      consecutive patients for evaluation of biliary duct dilatation found incidentally
      on computed tomography (CT) or ultrasound (US). MRCP scans were reviewed, and
      data were retrospectively collected on demographics and laboratory work-up.
      Patients were divided by the presence of a significant or non-significant MRCP
      findings explaining the biliary duct dilatation and compared for normal or
      abnormal liver function. RESULTS: Liver function was normal in 47 patients and
      abnormal in 21 patients. MRCP identified the cause of the bile duct dilatation in
      41 patients (60.3%). Rates of insignificant causes were 51% in the normal-liver
      function group and 7% in the abnormal-function group. Corresponding rates of
      significant causes were 27.7% and 61.9% (p = 0.007). CONCLUSIONS: MRCP is a
      valuable tool in the work-up of biliary duct dilatation. Although significantly
      more significant causes of bile dilatation are identified in patients with
      abnormal liver function, almost one-third of patients with normal liver function
      need further work-up. This has important implications for establishing criteria
      for the use of MRCP in asymptomatic patients with biliary dilatation.

PMID- 28507751
TI  - Validation of the efficacy of the prognostic factor score in the Japanese
      severity criteria for severe acute pancreatitis: A large multicenter study.
AB  - BACKGROUND: The Japanese severity criteria for acute pancreatitis (AP), which
      consist of a prognostic factor score and contrast-enhanced computed tomography
      grade, have been widely used in Japan. OBJECTIVE: This large multicenter
      retrospective study was conducted to validate the predictive value of the
      prognostic factor score for mortality and complications in severe AP patients in
      comparison to the Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score. METHODS: Data of 1159 patients diagnosed with severe AP according to the
      Japanese severity criteria for AP were retrospectively collected in 44
      institutions. RESULTS: The area under the curve (AUC) for the receiver-operating
      characteristic curve of the prognostic factor score for predicting mortality was
      0.78 (95% confidence interval (CI), 0.74-0.82), whereas the AUC for the APACHE II
      score was 0.80 (95% CI, 0.76-0.83), respectively. There were no significant
      differences in the AUC for predicting mortality between two scoring systems. The
      AUCs of the prognostic factor scores for predicting the need for mechanical
      ventilation, the development of pancreatic infection, and severe AP according to
      the revised Atlanta classification were 0.84 (95% CI, 0.81-0.86), 0.73 (95% CI,
      0.69-0.77), and 0.83 (95% CI, 0.81-0.86), respectively, which were significantly
      greater than the AUCs for the APACHE II score; 0.81 (95% CI, 0.78-0.83) for the
      need for mechanical ventilation (p = 0.03), 0.68 (95% CI, 0.63-0.72) for the
      development of pancreatic infection (p = 0.02), and 0.80 (95% CI, 0.77-0.82) for
      severe AP according to the revised Atlanta classification (p = 0.01). CONCLUSION:
      The prognostic factor score has an equivalent ability for predicting mortality
      compared with the APACHE II score. Regarding the ability for predicting the
      development of severe complications during the clinical course of AP, the
      prognostic factor score may be superior to the APACHE II score.

PMID- 28507754
TI  - Significantly higher rates of multiple and proximally located adenomas among
      patients with diabetes mellitus: A cross-sectional population-based study.
AB  - BACKGROUND: Diabetes mellitus (DM) is associated with a greater risk for
      colorectal cancer (CRC). OBJECTIVE: The objective of this article is to examine
      the endoscopic phenotype and histopathology of colorectal polyps in patients with
      vs without DM. METHODS: We conducted a cross-sectional study of patients who
      underwent colonoscopy at our university hospital and who completed a
      questionnaire. We collected endoscopy and histopathology data regarding
      colorectal adenomas and serrated polyps. Cox regression analyses were used to
      estimate adjusted prevalence ratios (PRs). RESULTS: We examined a total of 3654
      patients (mean age (SD): 62 (12) years, 47% males). Of them, 360 (9.9%) had DM.
      Overall, the prevalence of colorectal adenomas (42% vs 32%, p < 0.01), multiple
      (>=3) adenomas (12% vs 7%, p = 0.01) and proximal adenomas (30% vs 19%, p < 0.01)
      was higher in patients with vs without DM. Multivariable analysis showed that the
      prevalence of adenomas (PR 1.17, 95% CI; 1.02-1.34), multiple (PR 1.37, 95% CI;
      1.00-1.86) and proximal (PR 1.37, 95% CI; 1.16-1.62) adenomas was higher in
      patients with vs without DM, especially in men. CONCLUSION: Patients with DM
      harbor more frequently multiple and proximal adenomas than those without DM.
      Close colonoscopic surveillance of DM patients is important to maximize the
      effectiveness of colonoscopic CRC prevention.

PMID- 28507755
TI  - Ethnic variations in the occurrence of colonic neoplasms.
AB  - BACKGROUND AND AIMS: With the exception of African Americans and Hispanics, few
      studies have dealt with the influence of other types of ethnicity on the
      prevalence of colon polyps and colorectal cancer. The present study was
      undertaken to compare the ethnic and socioeconomic distributions of colonic
      neoplasms among different ethnic groups in the United States. METHODS: A total of
      813,057 patients, who underwent colonoscopy during 2008-2014, were recruited from
      an electronic database of histopathology reports (Miraca Life Sciences) for a
      cross-sectional study. Using multivariate logistic regression analyses, the
      presence of hyperplastic polyps, serrated adenomas, tubular adenomas, or
      adenocarcinomas each served as separate outcome variables. Patient ethnicity was
      determined using a name-based computer algorithm. Demographic (age, sex,
      ethnicity) and a variety of socioeconomic risk factors (associated with patients'
      ZIP code) served as predictor variables. RESULTS: About 50% of the study
      population harbored adenomatous polyps, 25% hyperplastic polyps, 8% serrated
      adenomas, and 1.4% adenocarcinomas. Tubular adenomas and adenocarcinomas showed
      similar ethnic distributions, being slightly more common among Hispanics and East
      Asians. All four types of colonic neoplasm were relatively rare among patients of
      Asian-Indian descent and relatively common among patients of Japanese descent.
      Except for Japanese patients, serrated adenomas tended to be less prevalent among
      East Asians. In general, markers of high socioeconomic status showed a tendency
      to be negatively associated with the presence of tubular adenoma and
      adenocarcinoma, but positively with the presence of serrated adenoma. CONCLUSION:
      Ethnicity and socioeconomic factors affect different histology types of polyps
      differently. Genetic as well as environmental factors interact in the development
      of colorectal cancer and its precursor lesions.

PMID- 28507756
TI  - Predictive factors of short-term mortality in ischaemic colitis and development
      of a new prognostic scoring model of in-hospital mortality.
AB  - BACKGROUND: Ischaemic colitis (IC) is the most common form of intestinal
      ischaemia with a wide spectrum of severity, with possible risk of death.
      OBJECTIVE: The purpose of this study was to evaluate predictive factors of in
      hospital and short-term mortality, in a cohort of patients with IC. METHODS:
      Retrospective analysis of IC cases diagnosed between 2008-2013 in a single
      tertiary centre, with assessment of factors at the time of diagnosis associated
      with in-hospital and 90-day mortality. RESULTS: Of the 203 patients included (132
      women), 47 (23%) died during the follow-up (median: 16 months). There were 21
      patients (45%) who died during hospitalization and at 90 days there were 30
      deaths (64% of total). In multivariate analysis, need for vasopressor support
      (odds ratio (OR) 11.21; 95% confidence interval (CI): 2.31-54.24; p = 0.01),
      Intermediate or Intensive Care Unit (ICU): admission (OR 7.01; 95% CI: 1.48
      33.16; p = 0.014) and atrial fibrillation (OR 4.99; 95% CI: 1.1-26.23; p = 0.048)
      were independently and significantly associated with in-hospital mortality. Using
      the coefficients of the estimated logistic model, we calculated a scoring model
      to predict the occurrence of in-hospital mortality. The presence of all three
      risk factors predicted a probability of death of 32% with an area under the
      receiver operating characteristic curve (AUROC) of 0.89 (95% CI 0.80-0.98. At 90
      days, the presence of chronic kidney disease (OR 7.46; 95% CI: 1.87-29.73; p =
      0.002), and male sex (OR 5.85; 95% CI: 1.57-21.83; p = 0.009) were also
      independently associated with mortality. CONCLUSIONS: Most deaths in ischaemic
      colitis occur in the first 90 days after admission, sharing similar risk factors.
      Assessment of the presence of atrial fibrillation, need of vasopressor support or
      hospitalization in the intermediate/intensive care unit provides a useful tool to
      estimate in-hospital mortality and to establish the management for patients
      admitted for ischaemic colitis.

PMID- 28507757
TI  - Risk of post-colonoscopy colorectal cancer due to incomplete adenoma resection: A
      nationwide, population-based cohort study.
AB  - BACKGROUND: Most post-colonoscopy colorectal cancers (PC-CRCs) are thought to
      develop from missed or incompletely resected adenomas. AIMS: We aimed to assess
      the incidence rate of PC-CRC overall and per colorectal segment, as a proxy for
      PC-CRC due to incomplete adenoma resection, and to identify adenoma
      characteristics associated with these PC-CRCs. METHODS: We performed a
      nationwide, population-based cohort study, including all patients with a first
      colorectal adenoma between 2000-2010 in the Dutch Pathology Registry (PALGA).
      Outcomes were the incidence rate of PC-CRC overall and of PC-CRC in the same
      colorectal segment, occurring between six months and five years after adenoma
      resection. A multivariable Cox proportional hazard analysis was performed to
      identify factors associated with PC-CRCs in the same segment. RESULTS: We
      included 107,744 patients (mean age 63.4 years; 53.6% male). PC-CRC was detected
      in 1031 patients (0.96%) with an incidence rate of 1.88 per 1000 person years. PC
      CRC in the same segment was found in 323 of 133,519 adenomas (0.24%) with an
      incidence rate of 0.56 per 1000 years of follow-up. High-grade dysplasia (hazard
      ratio (HR) 2.54, 95% confidence interval (CI) 1.99-3.25) and both villous (HR
      2.63, 95% CI 1.79-3.87) and tubulovillous histology (HR 1.80, 95% CI 1.43-2.27)
      were risk factors for PC-CRC in the same segment. CONCLUSIONS: Approximately one
      third of PC-CRCs are found in the same colorectal segment after adenoma resection
      and could therefore be a consequence of incomplete adenoma resection, occurring
      in one in 400 adenomas. The risk of PC-CRC in the same segment is increased in
      adenomas with high-grade dysplasia or (tubulo)villous histology.

PMID- 28507759
TI  - Emerging local ablative therapies for unresectable perihilar cholangiocarinoma:
      Time for re-appraisal.

PMID- 28507758
TI  - Fecal immunochemical test-based colorectal cancer screening: The gender dilemma.
AB  - BACKGROUND: Despite differences between men and women in incidence of colorectal
      cancer (CRC) and its precursors, screening programs consistently use the same
      strategy for both genders. OBJECTIVE: The objective of this article is to
      illustrate the effects of gender-tailored screening, including the effects on
      miss rates of advanced neoplasia (AN). METHODS: Participants (age 50-75 years) in
      a colonoscopy screening program were asked to complete a fecal immunochemical
      test (FIT) before colonoscopy. Positivity rates, sensitivity and specificity for
      detection of AN at multiple cut-offs were determined. Absolute numbers of
      detected and missed AN per 1000 screenees were calculated. RESULTS: In total
      1,256 individuals underwent FIT and colonoscopy, 51% male (median age 61 years;
      IQR 56-66) and 49% female (median age 60 years; IQR 55-65). At all cut-offs men
      had higher positivity rates than women, ranging from 3.8% to 10.8% versus 3.2% to
      4.8%. Sensitivity for AN was higher in men than women; 40%-25% and 35%-22%,
      respectively. More AN were found and missed in absolute numbers in men at all cut
      offs. CONCLUSION: More AN were both detected and missed in men compared to women
      at all cut-offs. Gender-tailored cut-offs could either level sensitivity in men
      and women (i.e., lower cut-off in women) or level the amount of missed lesions
      (i.e., lower cut-off in men).

PMID- 28507760
TI  - Young GI Angle - Harmonised education: the EBGH Blue Book.

PMID- 28507761
TI  - The European Section and Board of Gastroenterology and Hepatology.

PMID- 28507762
TI  - Circulating tumor cell clusters-associated gene plakoglobin is a significant
      prognostic predictor in patients with breast cancer.
AB  - BACKGROUND: Circulating tumor cells (CTCs) are linked to metastatic relapse and
      are regarded as a prognostic marker for human cancer. High expression of
      plakoglobin, a cell adhesion protein, within the primary tumor is positively
      associated with CTC clusters in breast cancer. In this study, we investigated the
      correlation between plakoglobin expression and survival of breast cancer.
      METHODS: We evaluated 121 breast cancer patients treated with neoadjuvant
      chemotherapy. Expression of plakoglobin was identified by immunohistochemical
      staining in the cell membrane. We also examined the relation between the
      expression of plakoglobin and E-cadherin, an epithelial-mesenchymal transition
      (EMT) marker. RESULTS: Patients with high plakoglobin expression had
      significantly worse distant-metastasis-free survival (DMFS) (P = 0.016, log
      rank). Plakoglobin expression had no correlation with pathological complete
      response rate (P = 0.627). On univariate analysis with respect to distant
      metastasis, high plakoglobin expression showed worse prognosis than low
      plakoglobin expression [P = 0.036, hazard ratio (HR) = 3.719]. Multivariate
      analysis found the same result (P = 0.013, HR = 5.052). In addition, there was a
      significant relationship between the expression of plakoglobin and E-cadherin (P
      = 0.023). CONCLUSIONS: Plakoglobin expression is an independent prognostic factor
      in patients with breast cancer, particularly for DMFS, and this is related to
      EMT.

PMID- 28507763
TI  - Investigation of cloud point extraction for the analysis of metallic
      nanoparticles in a soil matrix.
AB  - The characterization of manufactured nanoparticles (MNPs) in environmental
      samples is necessary to assess their behavior, fate and potential toxicity.
      Several techniques are available, but the limit of detection (LOD) is often too
      high for environmentally relevant concentrations. Therefore, pre-concentration of
      MNPs is an important component in the sample preparation step, in order to apply
      analytical tools with a LOD higher than the ng kg-1 level. The objective of this
      study was to explore cloud point extraction (CPE) as a viable method to pre
      concentrate gold nanoparticles (AuNPs), as a model MNP, spiked into a soil
      extract matrix. To that end, different extraction conditions and surface coatings
      were evaluated in a simple matrix. The CPE method was then applied to soil
      extract samples spiked with AuNPs. Total gold, determined by inductively coupled
      plasma mass spectrometry (ICP-MS) following acid digestion, yielded a recovery
      greater than 90 %. The first known application of single particle ICP-MS and
      asymmetric flow field-flow fractionation to evaluate the preservation of the AuNP
      physical state following CPE extraction is demonstrated.

PMID- 28507764
TI  - 'Actinomyces provencensis' sp. nov., 'Corynebacterium bouchesdurhonense' sp.
      nov., 'Corynebacterium provencense' sp. nov. and 'Xanthomonas massiliensis' sp.
      nov., 4 new species isolated from fresh stools of obese French patients.
AB  - We report the main characteristics of 'Actinomyces provencensis' strain SN12T sp.
      nov., 'Corynebacterium bouchesdurhonense' strain SN14T sp. nov., 'Corynebacterium
      provencense' strain SN15T sp. nov. and 'Xanthomonas massiliensis' strain SN8T sp.
      nov., which were all isolated from stool samples from obese French patients.

PMID- 28507765
TI  - Asthma: epidemiology of disease control in Latin America - short review.
AB  - Asthma is reported as one of the most common chronic diseases in childhood,
      impairing the quality of life of patients and their families and incurring high
      costs to the healthcare system and society. Despite the development of new drugs
      and the availability of international treatment guidelines, asthma is still
      poorly controlled, especially in Latin America. Original and review articles on
      asthma control or epidemiology with high levels of evidence have been selected
      for analysis among those published in PubMed referenced journals during the last
      20 years, using the following keywords: "asthma control" combined with "Latin
      America", " epidemiology", "prevalence", "burden", "mortality", "treatment and
      unmet needs", "children", "adolescents", and "infants". There was a high
      prevalence and severity of asthma during the period analyzed, especially in
      children and adolescents. Wheezing in infants was a significant reason for
      seeking medical care in Latin American health centers. Moreover, the frequent use
      of quick-relief bronchodilators and oral corticosteroids by these patients
      indicates the lack of a policy for providing better care for asthmatic patients,
      as well as poor asthma control. Among adults, studies document poor treatment and
      control of the disease, as revealed by low adherence to routine anti-inflammatory
      medications and high rates of emergency care visits and hospitalization. In
      conclusion, although rare, studies on asthma control in Latin America repeatedly
      show that patients are inadequately controlled and frequently overestimate their
      degree of asthma control according to the criteria used by international asthma
      treatment guidelines. Additional education for doctors and patients is essential
      for adequate control of this illness, and therefore also for reduction of the
      individual and social burden of asthma.

PMID- 28507766
TI  - Effect of dietary mannanoligosaccharide supplementation on nutrient
      digestibility, hindgut fermentation, immune response and antioxidant indices in
      dogs.
AB  - BACKGROUND: Use of prebiotics in companion animal nutrition is often considered
      advantageous over probiotics because of the ease of handling, ability to
      withstand processing and storage etc. While most of the studies on prebiotic use
      in dogs have been done with processed food as basal diet, the response in
      relation to homemade diet feeding is not very well explored. METHODS: The study
      was conducted to evaluate the effects of dietary mannanoligosaccharide (MOS)
      supplementation on nutrient digestibility, hindgut fermentation, immune response
      and antioxidant indices in dogs. Ten Spitz pups were divided into two groups:
      control (CON) with no supplementation, and experimental (MOS) wherein the basal
      diet was supplemented with MOS at 15 g/kg diet. All dogs were fed on a home
      prepared diet for a period of 150 days. The study protocol included a digestion
      trial, periodic blood collection and analysis for lipid profile and erythrocytic
      antioxidants. Immune response of the animals was assessed towards the end of the
      feeding period. RESULTS: Results revealed no significant (P > 0.05) variations in
      palatability score, intake and apparent digestibility of nutrients between the
      groups. Faecal score, faeces voided, faecal pH, concentrations of ammonia,
      lactate and short-chain fatty acids were comparable (P > 0.05) between the two
      groups. Cell-mediated immune response, assessed as delayed-type of
      hypersensitivity response, was significantly higher (P < 0.05) in the MOS group.
      The percent of lymphocyte sub-populations CD4+ and ratio of CD4+:CD8+ were also
      significantly (P < 0.05) higher in MOS group. The serum IgG levels were similar
      (P > 0.05) in both the groups. Supplementation of MOS lowered (P < 0.05) serum
      total- and LDL- cholesterol levels, when compared with the control group. The
      erythrocytic antioxidant indices were similar (P > 0.05) between the two groups.
      CONCLUSIONS: The results indicated that supplementation of MOS at the rate of 15
      g/kg in the diet of dog augmented the cell-mediated immune response and serum
      lipid profile without any influences on digestibility of nutrients, hindgut
      fermentation and antioxidants indices.

PMID- 28507767
TI  - Post-traumatic stress in pregnant women with primary cytomegalovirus infection
      and risk of congenital infection in newborns.
AB  - BACKGROUND: Substantial evidence indicates that perinatal mental disturbances are
      associated with the risk for negative maternal-newborn outcomes. A neuroendocrine
      brain-placenta interaction has been described to explain the association between
      prenatal stress-related disorders and placental abnormalities. Whether these
      mechanisms may affect the likelihood of mother-to-child transmission (MTCT) of
      infections has never been investigated. AIMS: To evaluate the role of
      psychological factors in cytomegalovirus (CMV) MTCT in pregnant women with
      primary CMV infection. METHOD: A cohort of 276 pregnant women with primary CMV
      infection underwent assessment of (a) reactive psychopathological symptoms, such
      as current depressive symptoms and ongoing symptoms of post-traumatic stress
      disorder; and (b) stable personality traits, such as alexithymia and Type D
      (distressed) personality. Congenital infection was diagnosed by CMV DNA
      amplification from blood and/or urine and saliva from newborn at birth. RESULTS:
      The occurrence of congenital CMV disease in the newborn was independently
      predicted by post-traumatic stress symptoms during pregnancy. CONCLUSIONS: Our
      findings suggest that psychological stress-related disturbances may weaken the
      physical and immunological barrier against the mother-to-fetus transmission of
      viruses. DECLARATION OF INTEREST: We declare that we have no conflicting
      interests to disclose. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507768
TI  - In-patient suicide: selection of people at risk, failure of protection and the
      possibility of causation.
AB  - BACKGROUND: Being a current psychiatric in-patient is one of the strongest
      statistical risk factors for suicide. It is usually assumed that this strong
      association is not causal but is a result of the combination of the selection of
      high-risk patients for admission and the imperfect protection from suicide
      afforded by psychiatric wards. Logically, a third factor, which is causal, might
      play a role in the association. It has recently been suggested that adverse
      experiences in psychiatric units such as trauma, stigma and loss of social role
      might precipitate some in-patient suicides. AIMS: To consider whether there is a
      causal association between psychiatric hospitalisation and suicide. METHOD: We
      used the framework of Austin Bradford Hill's criteria for assessing causality in
      epidemiology to consider the possibility that psychiatric hospitalisation might
      causally contribute to the extent and variation in in-patient suicide rates.
      RESULTS: The association between psychiatric hospitalisation and suicide clearly
      meets five of the nine Hill's criteria (strength of association, consistency,
      plausibility, coherence and analogy) and partially meets three of the remaining
      four criteria (gradient of exposure, temporality and experimental evidence).
      CONCLUSIONS: Admission to hospital itself might play a causal role in a
      proportion of in-patient suicides. The safety of being in hospital with respect
      to suicide could be examined with a large-scale randomised controlled trial
      (RCT). In the absence of an RCT, the possibility of a causal role provides
      further impetus to calls to make care in the community more available and
      psychiatric hospitals more acceptable to patients. DECLARATION OF INTEREST:
      M.M.L. and C.J.R. have provided expert testimony in legal proceedings following
      in-patient suicide. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists
      2017. This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507769
TI  - A National Quality Improvement Collaborative for the clinical use of outcome
      measurement in specialised mental healthcare: results from a parallel group
      design and a nested cluster randomised controlled trial.
AB  - BACKGROUND: Although the importance and advantages of measurement-based care in
      mental healthcare are well established, implementation in daily practice is
      complex and far from optimal. AIMS: To accelerate the implementation of outcome
      measurement in routine clinical practice, a government-sponsored National Quality
      Improvement Collaborative was initiated in Dutch-specialised mental healthcare.
      METHOD: To investigate the effects of this initiative, we combined a matched-pair
      parallel group design (21 teams) with a cluster randomised controlled trial (RCT)
      (6 teams). At the beginning and end, the primary outcome 'actual use and
      perceived clinical utility of outcome measurement' was assessed. RESULTS: In both
      designs, intervention teams demonstrated a significant higher level of
      implementation of outcome measurement than control teams. Overall effects were
      large (parallel group d=0.99; RCT d=1.25). CONCLUSIONS: The National
      Collaborative successfully improved the use of outcome measurement in routine
      clinical practice. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The
      Royal College of Psychiatrists 2017. This is an open access article distributed
      under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC
      ND) license.

PMID- 28507771
TI  - Association between suicidal symptoms and repeat suicidal behaviour within a
      sample of hospital-treated suicide attempters.
AB  - BACKGROUND: Suicidal behaviour is the end result of the complex relation between
      many factors which are biological, psychological and environmental in nature.
      Network analysis is a novel method that may help us better understand the complex
      association between different factors. AIMS: To examine the relationship between
      suicidal symptoms as assessed by the Beck Scale for Suicide Ideation and future
      suicidal behaviour in patients admitted to hospital following a suicide attempt,
      using network analysis. METHOD: Secondary analysis was conducted on previously
      collected data from a sample of 366 patients who were admitted to a Scottish
      hospital following a suicide attempt. Network models were estimated to visualise
      and test the association between baseline symptom network structure and suicidal
      behaviour at 15-month follow-up. RESULTS: Network analysis showed that the desire
      for an active attempt was found to be the most central, strongly related suicide
      symptom. Of the 19 suicide symptoms that were assessed at baseline, 10 symptoms
      were directly related to repeat suicidal behaviour. When comparing baseline
      network structure of repeaters (n=94) with the network of non-repeaters (n=272),
      no significant differences were found. CONCLUSIONS: Network analysis can help us
      better understand suicidal behaviour by visualising the complex relation between
      relevant symptoms and by indicating which symptoms are most central within the
      network. These insights have theoretical implications as well as informing the
      assessment and treatment of suicidal behaviour. DECLARATION OF INTEREST: None.
      COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017. This is an open
      access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507770
TI  - The recovery of factors associated with decision-making capacity in individuals
      with psychosis.
AB  - BACKGROUND: There is limited data on the recovery of factors associated with
      decisional capacity in patients with psychosis. AIMS: To study the relationship
      between changes in mental capacity, symptoms and global functioning using
      structured measures during treatment for psychosis. METHOD: Fifty-six patients
      with psychosis were assessed for capacity to consent to treatment on admission
      and at 6 and 12 weeks following treatment. The MacArthur Competence Assessment
      Tool - Treatment, the Positive and Negative Symptom Scale and the Global
      Assessment of Functioning Scale were used to measure mental capacities, symptom
      severity and global functioning respectively. Treating consultants rated capacity
      to consent, masked to these measures. RESULTS: Greater impairments on all
      measures were found in patients assessed as lacking capacity. These improved with
      treatment over 12 weeks with significant effect sizes (0.5 to 0.6). Stronger
      correlations between mental capacities, positive symptoms (-0.47) and global
      functioning (0.56) were noted in the first 6 weeks. CONCLUSIONS: Impairments in
      capacity in acute stages of psychosis are related to symptom severity and
      functional impairment. They improve during treatment, particularly in the first 6
      weeks. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College
      of Psychiatrists 2017. This is an open access article distributed under the terms
      of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507773
TI  - Rapid-onset clozapine-induced loss of glycaemic control: case report.
AB  - : Clozapine has proved to be an effective antipsychotic for the treatment of
      refractory schizophrenia - characterised by the persistence of symptoms despite
      optimal treatment trials with at least two different antipsychotics at adequate
      dose and duration - but its use is hampered by adverse effects. The development
      of clozapine-induced diabetes is commonly considered to arise as part of a
      metabolic syndrome, associated with weight gain, and thus evolves slowly. We
      present the case of an individual with refractory schizophrenia and metformin
      controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia
      immediately after starting clozapine. Given the refractory nature of his illness,
      the decision was made to continue clozapine and manage the diabetes. This case
      supports the existence of a more direct mechanism by which clozapine alters
      glycaemic control, aside from the more routine slow development of a metabolic
      syndrome. DECLARATION OF INTEREST: S.S.S. is supported by a European Research
      Council Consolidator Award (Grant Number 311686) and the National Institute for
      Health Research (NIHR) Mental Health Biomedical Research Centre at South London
      and Maudsley NHS Foundation Trust and King's College London. The funders had no
      role in study design, data collection, data analysis, data interpretation or
      writing of the report. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2017. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507772
TI  - Clinically significant depressive symptoms and sexual behaviour among men who
      have sex with men.
AB  - BACKGROUND: The relationship between depression and sexual behaviour among men
      who have sex with men (MSM) is poorly understood. AIMS: To investigate prevalence
      and correlates of depressive symptoms (Patient Health Questionnaire-9 score >=10)
      and the relationship between depressive symptoms and sexual behaviour among MSM
      reporting recent sex. METHOD: The Attitudes to and Understanding of Risk of
      Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary
      medicine clinic attendees without diagnosed HIV (2013-2014). RESULTS: Among 1340
      MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic
      disadvantage and lower supportive network. Adjusted for key sociodemographic
      factors, depressive symptoms were associated with measures of condomless sex
      partners in the past 3 months (>=2 (prevalence ratio (PR) 1.42, 95% CI 1.17-1.74;
      P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20-1.71; P<0.001)),
      sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19-1.79;
      P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33
      2.50; P<0.001). CONCLUSIONS: Management of mental health may play a role in HIV
      and STI prevention. DECLARATION OF INTEREST: A.N.P. has received payments for
      presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has
      received support for attendance at conferences, speaker fees and payments for
      attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen
      Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead
      Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G.
      has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the
      BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and
      Novartis. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017. This
      is an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507774
TI  - Footnotes to Kraepelin: changes in the classification of mood disorders with DSM
      5.
AB  - SUMMARY: Reliable diagnosis of mood disorders continues to pose a challenge. This
      is surprising because they have been recognised clinically since classical times.
      Mood disorders are also common: major depressive disorder affects nearly 300
      million people worldwide and bipolar affective disorder nearly 60 million and
      they are a major cause of disability. Nonetheless, the reliability trials of the
      updated Diagnostic and Statistical Manual, Fifth Edition (DSM-5) found that the
      reliability of the diagnosis of major depressive disorder was in the
      'questionable' range. Although the reliability of the diagnosis of bipolar I
      disorder in the same trials was 'good', the sample size of the individuals
      recruited to validate bipolar II disorder was insufficient to confirm
      reliability. As the epidemiological prevalences of bipolar I and bipolar II
      disorders are the same, this alone implies problems in its recognition. Here, we
      critically evaluate the most recent iteration of DSM mood disorder diagnoses in a
      historical light and set out the implications for clinical practice and research.
      DECLARATION OF INTEREST: N.J.K. has attended educational activities funded by
      GlaxoSmithKline (GSK) and by Lundbeck and has worked on data from a study funded
      by Wyeth; her PhD was jointly funded by the Wellcome Trust and GSK. A.H.Y. has
      given paid lectures and is on advisory boards for the following companies with
      drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Janssen,
      Lundeck, Sunovion, Servier, Livanova. He is Lead Investigator for the Embolden
      Study (Astrazenaca), BCI Neuroplasticity study and Aripiprazole Mania Study,
      which are investigator-initiated studies from Astrazenaca, Eli Lilly, Lundbeck,
      and Wyeth. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017. This
      is an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28507775
TI  - Thoracolumbar fractures without neurological impairment: A review of diagnosis
      and treatment.
AB  - An appropriate protocol and unified management of thoracolumbar fractures without
      neurological impairment has not been well defined.This review attempts to
      elucidate some controversies regarding diagnostic tools, the ability to define
      the most appropriate treatment of classification systems and the evidence for
      conservative and surgical methods based on the recent literature. Cite this
      article: Vila-Canet G, Garcia de Frutos A, Covaro A, Ubierna MT, Caceres E.
      Thoracolumbar fractures without neurological impairment: a review of diagnosis
      and treatment. EFORT Open Rev 2016;1:332-338. DOI: 10.1302/2058-5241.1.000029.

PMID- 28507776
TI  - The current situation in hip arthroscopy.
AB  - Hip arthroscopy is an evolving surgical technique that has recently increased in
      popularity.Although femoroacetabular impingement was an important launch pad for
      this technique, extra-articular pathology has been described through hip
      endoscopy.Good clinical results in the medium term will allow improvements in
      this technique and increase its indications. Cite this article: EFORT Open Rev
      2017;2:58-65. DOI: 10.1302/2058-5241.2.150041.

PMID- 28507780
TI  - Current concepts in elbow arthroplasty.
AB  - Distal humeral replacement and the total elbow are two commonly-used
      arthroplastiesEach prosthesis has evolving indications and surgical
      techniquesRecent changes in device design and implantation methods are due to
      biomechanical and clinical outcome-based researchNew prostheses and methods
      provide: better elbow kinematics, more durable bearings and longer-lasting joint
      replacement potential Cite this article: EFORT Open Rev 2017;2:83-88. DOI:
      10.1302/2058-5241.2.160064.

PMID- 28507777
TI  - The role of isolated polyethylene exchange in total knee arthroplasty.
AB  - The use of modular total knee arthroplasty (TKA) implants allows surgeons to
      perform isolated tibial polyethylene insert exchange (IPE) while retaining well
      fixed and stable components.The purported advantages of IPE include preservation
      of bone stock, shorter operating time, less blood loss, faster rehabilitation and
      lower cost. However, the indications for IPE are limited.IPE for wear and
      osteolysis has moderate success in the medium term but should be avoided in cases
      of accelerated wear. In selected cases, debridement and IPE for early infection
      can result in low morbidity with high success rates in the short term. IPE for
      arthrofibrosis has poor results.IPE should be undertaken with caution and an
      institutional algorithm should be followed. Cite this article: EFORT Open Rev
      2017;2:66-71 DOI: 10.1302/2058-5241.2.160049.

PMID- 28507779
TI  - Spinal osteotomies: indications, limits and pitfalls.
AB  - The aims of spinal deformity surgery are to achieve balance, relieve pain and
      prevent recurrence or worsening of the deformity.The main types of osteotomies
      are the Smith-Petersen osteotomy (SPO), pedicle subtraction osteotomy (PSO), bone
      disc-bone osteotomy (BDBO) and vertebral column resection (VCR), in order of
      increasing complexity.SPO is a posterior column osteotomy in which the posterior
      ligaments and the facet joints are removed and correction is performed through
      the disc space. A mobile anterior disc is essential. SPO is best in patients with
      +6-8 cm C7 plumbline. The amount of correction is 9.3 degrees  to 10.7 degrees
      /level (1 degrees /mm bone).PSO is a technique where the posterior elements and
      pedicles are removed. Then a triangular wedge through the pedicles is removed and
      the posterior spine is shortened using the anterior cortex as a hinge. The ideal
      candidates are patients with a severe sagittal imbalance. A single level
      osteotomy can produce 30 degrees  40 degrees  of correction. A single level
      osteotomy may restore global sagittal balance by an average of 9 cm with an upper
      limit of 19 cm.BDBO is an osteotomy done above and below a disc level. A BDBO
      provides correction rates in the range of 35 degrees  to 60 degrees . The main
      indications are deformities with the disc space as the apex and severe sagittal
      plane deformities.VCR is indicated for rigid multi-planar deformities, sharp
      angulated deformities, hemivertebra resections, resectable spinal tumours, post
      traumatic deformities and spondyloptosis. The main indication for a VCR is fixed
      coronal plane deformity.The type of osteotomy must be chosen mainly according to
      the aetiology, type and apex of the deformity. One may start with SPOs and may
      gradually advance to complex osteotomies. Cite this article: EFORT Open Rev
      2017;2:73-82. DOI: 10.1302/2058-5241.2.160069.

PMID- 28507781
TI  - Isolated posterior cruciate ligament tears: an update of management.
AB  - Isolated posterior cruciate ligament (PCL) tears are much less frequent than
      anterior cruciate ligament (ACL) tears.Abrupt posterior tibial translation (such
      as dashboard impact), falls in hyperflexion and direct hyperextension trauma are
      the most frequent mechanisms of production.The anterolateral bundle represents
      two-thirds of PCL mass and is reconstructed in single-bundle techniques.The PCL
      has an intrinsic capability for healing. This is the reason why, nowadays, the
      majority of isolated PCL tears are managed non-operatively, with rehabilitation
      and bracing.Recent studies have focused on double-bundle reconstruction
      techniques, as they seem to restore knee kinematics.No significant clinical
      differences have been established between single versus double-bundle techniques,
      autograft versus allograft, transtibial tunnel versus tibial inlay techniques or
      remnant-preserving versus remnant-release techniques. Cite this article: EFORT
      Open Rev 2017;2:89-96. DOI: 10.1302/2058-5241.2.160009.

PMID- 28507782
TI  - Surgical treatment of acetabular fractures in the elderly: a systematic review of
      the results.
AB  - We performed a systematic review of the literature involving a number of
      databases to identify studies that included outcomes of surgical treatment of
      acetabular fractures in patients aged > 55 years. An initial search identified
      1564 studies. After exclusion by two independent reviewers, 15 studies met the
      inclusion criteria. All studies were case series and the mean Coleman Methodology
      score for methodological quality assessment was 43.7 (standard deviation 12.3).
      There were 354 patients with acetabular fractures. Pooled analysis revealed a
      mean age of 71.6 years (55 to 96) and a mean follow-up of 43 months (20 to 188).
      Complex fractures were reported in 70.1% of patients.Seven studies presented the
      results of open reduction and internal fixation (ORIF); in eight other studies a
      total hip arthroplasty (THA), alone or combined with different internal fixation
      techniques, was the chosen treatment. In the ORIF sub-group, conversion to THA
      was performed at a mean of 25.5 months with anatomical reduction in 11.6% and
      imperfect and poor reduction in 22.3%. In the THA sub-group, an acetabular ring
      or cage with a cemented acetabular component was used in four studies (52
      patients) and a cementless acetabular component was implanted in five studies (78
      patients). Six patients (4.9%) underwent revision at a mean of 39 months after
      the index procedure.The analysis of intra-operative and post-operative parameters
      showed a statistical difference between the two sub-groups with regards to the
      mean operating time (236 mins ORIF vs 178 mins THA), the mean blood loss (707 mL
      ORIF vs 974 mL THA) and the mean mortality rate at one year (22.6% ORIF vs 8.8%
      THA).Based on the current data available, acute THA (alone or in combination with
      internal fixation) may have a role in the treatment of older patients with
      complex acetabular fractures. Despite the wide heterogenecity of fracture types
      and patient co-morbidities, THA procedures were associated with lower rates of
      mortality and further surgery when compared with the ORIF procedures. Cite this
      article: EFORT Open Rev 2017;2:97-103. DOI: 10.1302/2058-5241.2.160036.

PMID- 28507784
TI  - Geraniin attenuates naloxone-precipitated morphine withdrawal and morphine
      induced tolerance in mice.
AB  - BACKGROUND AND AIM: Potentially life-threatening and unpleasant side effects
      associated with some analgesics have fueled the drive for the search for more
      analgesics with better side effect profiles. Geraniin, the most dominant
      secondary metabolite in the aqueous extract of the aerial parts of Phyllanthus
      muellerianus, has been shown to possess antinociceptive properties mediated
      partly by opioidergic mechanisms. The purpose of this study is to determine
      whether geraniin exhibits tolerance and if it is able to ameliorate withdrawal
      signs in naloxone-precipitated morphine withdrawal. MATERIALS AND METHODS: After
      chronic treatment of mice with geraniin orally, the formalin test was used to
      ascertain whether tolerance will develop to its antinociceptive effects and if
      there is morphine-induced tolerance cross-generalization with geraniin. The
      effect of geraniin on naloxone-precipitated morphine withdrawal signs in morphine
      dependent mice was also investigated. RESULTS: Geraniin (3-30 mg/kg) did not
      produce any tolerant effects after chronic administration and there was also no
      cross-generalization with the tolerant effects of morphine. Geraniin did not
      induce withdrawal signs but significantly reduced the number of jumps in morphine
      dependent mice. CONCLUSION: Geraniin does not produce any tolerant effects like
      morphine and also reduced the signs associated with naloxone-precipitated
      morphine withdrawal in mice.

PMID- 28507783
TI  - Periprosthetic shoulder infection: an overview.
AB  - Periprosthetic shoulder infection (PSI) is rare but potentially devastating. The
      rate of PSI is increased in cases of revision procedures, reverse shoulder
      implants and co-morbidities. One specific type of PSI is the occurrence of low
      grade infections caused by non-suppurative bacteria such as Propionibacterium
      acnes or Staphylococcus epidemermidis.Success of treatment depends on micro
      organism identification, appropriate surgical procedures and antibiotic
      administration efficiency. Post-operative early PSI can be treated with simple
      debridement, while chronic PSI requires a one- or two-stage revision procedure.
      Indication for one-time exchange is based on pre-operative identification of a
      causative agent. Resection arthroplasty remains an option for low-demand patients
      or recalcitrant infection. Cite this article: EFORT Open Rev 2017;2:104-109. DOI:
      10.1302/2058-5241.2.160023.

PMID- 28507786
TI  - Application of Hyperosmotic Nanoemulsions in Wound Healing: Partial Thickness
      Injury Model in Swine.
AB  - Objective: In this work, we introduce a novel hyperosmotic nanoemulsion (HNE)
      topical agent for use in wound healing. These topical emulsion complexes combine
      a lipophilic thymol nanoemulsion with a hyperosmotic saccharide matrix. This
      combination has been previously shown to possess synergistic antimicrobial
      activity against a host of common and drug-resistant pathogens in vitro.
      Approach: In this study, we present additional data to assess the safety and
      efficacy of these emulsions in a partial thickness injury model in swine. Ten
      wounds sized 2 * 3.5 cm were created in 18 pigs using an electrodermatome set at
      a depth of 0.76 mm. The wounds were subsequently contaminated with a cocktail of
      Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Candida
      albicans at 5 * 107 total colony forming unit per wound. Treatments were
      subdivided in the control group and emulsion concentrations at 0.0%, 0.01%,
      0.03%, and 0.063% thymol content. Longitudinal metrics for wound healing included
      rate of reepithelialization, wound bed color measurements, amount of wound
      exudate, wound swab culture data, and histological examination at 4, 7, and 14
      days. The cosmetics of the healed wound were obtained at day 14 with three
      dimensional photogrammetry. Results: Experimental results showed that HNE reduced
      the wound level bacteria count by ~0.5-1 log versus controls after 24 h. The
      amount of pathogen reduction was weakly correlated to the concentration of the
      emulsion. In addition, all HNE groups maintained a moist wound environment and
      showed increased fibrin formation and improved hemostatic response. Innovation:
      No significant difference in the rate of reepithelialization or wound closure was
      found between treatment concentrations and control groups. HNE treatment did not
      demonstrate any adverse host tissue response. Conclusion: These results suggest
      HNE may be a candidate for reducing wound bacterial counts without compromising
      reepithelialization.

PMID- 28507785
TI  - A Retrospective Chart Review of Chronic Wound Patients Treated with Topical
      Oxygen Therapy.
AB  - Objective: Topical oxygen devices are Food and Drug Administration (FDA) cleared
      for the following indications for use of various etiologies: skin ulcerations due
      to diabetes, venous stasis, postsurgical infections and gangrenous lesions,
      decubitus ulcers; amputations/infected stumps; skin grafts; burns; and frostbite.
      The goal of this study was to understand the impact of topical oxygen therapy
      (TOT) on patient outcomes, including amputation and healing rates. Approach: This
      retrospective chart review included records collected between January 1, 2007,
      and July 18, 2016, from male and female patients ranging in age from 4 years to
      105 years. All wounds were at least 1 cm2 and were treated with at least one
      separate modality before treatment with TOT and then treated with TOT for a
      minimum of 2 weeks in compliance with the FDA-approved indications. All records
      were from wounds that were no longer being treated with TOT. Results: In this
      study, TOT was associated with an overall rate of 59.4% for a reduction in
      chronic wound size, while 41.6% of wounds had no healing. The overall amputation
      rate was 2.4% for wounds in this study. Innovation: To our knowledge, this
      retrospective chart review represents one of the largest data sets (4,127 total
      wounds) collected over one of the longest time periods (9.5 years) to evaluate
      patient outcomes following TOT. Conclusion: This study revealed healing and
      amputation rates similar to those reported in controlled clinical studies using
      TOT to treat chronic wounds.

PMID- 28507787
TI  - The Feasibility of a Handheld Electrospinning Device for the Application of
      Nanofibrous Wound Dressings.
AB  - Objectives: The aim of this study was to determine the feasibility of a portable
      electrospinning device for the application of wound dressings. Approach: Four
      polymer nanofibers dressings were applied on superficial partial thickness wounds
      to a porcine model and compared with a traditional paraffin tulle gras dressing.
      The polymer nanofibrous dressings were applied using a handheld portable
      electrospinning device activated at a short distance from the wound. The partial
      thickness donor sites were evaluated on day 2, 7, and 14 when dressings were
      removed and tissue samples were taken for histological examination. Results: No
      significant difference was detected between the different electrospun nanofibrous
      dressings and traditional paraffin tulle gras. Desirable characteristics of the
      electrospun nanofiber dressing group included nontouch technique, ease of
      application, adherence and reduction in wound edema and inflammation. There was
      no delayed wound healing or signs of infection reported in both the electrospun
      nanofiber and traditional tulle gras dressings. Innovation: Used on partial
      thickness wounds, polymer electrospun nanofiber dressings provide excellent
      surface topography and are a nontouch, feasible, and safe method to promote wound
      healing with the potential to reduce wound infections. Such custom-made
      nanofibrous dressings have implications for the reduction of pain and trauma,
      number of dressing changes, scarring, and an added cost benefit. Conclusion: We
      have demonstrated that this portable handheld electrospinning device can be
      utilized for different formulations and materials and customized according to the
      characteristics of the target wound at the various stages of wound healing.

PMID- 28507788
TI  - Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte
      macrophage-colony-stimulating factor therapy expanded by dendritic cell and
      cytokine-induced killer cell adoptive therapy.
AB  - Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis,
      antigen release, and adaptive immune responses, systemic antitumor responses post
      therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC)
      and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We
      hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony
      stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could
      be expanded systemically with sequential DC-CIK therapy. Patients and Methods: We
      performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC
      CIK cell therapy. In addition to safety and clinical endpoints, we monitored
      adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre
      oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results:
      Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom
      seven experienced stable disease (SD). Five of the OVT treated patients underwent
      leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three
      progressed. T cell receptor sequencing of TCR beta sequences one month after OVT
      therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the
      majority of patients with the systematic expansion of multiple T cell clone
      populations following DC-CIK therapy. This treatment was well tolerated and long
      term event free and overall survival was observed in six of the nine patients.
      Conclusions: Strategies inducing the local activation of tumor-specific immune
      responses can be combined with adoptive cellular therapies to expand the adaptive
      T cell responses systemically and further studies are warranted.

PMID- 28507789
TI  - Calreticulin promotes immunity and type I interferon-dependent survival in mice
      with acute myeloid leukemia.
AB  - Exposure of cancer cells to particular chemotherapeutic agents or gamma
      irradiation induces a form of cell death that stimulates an immune response in
      mice. This "immunogenic cell death" requires calreticulin (CRT) translocation to
      the plasma membrane, which has been shown to promote cancer cell phagocytosis.
      However, it remains unclear whether the effect of CRT on cancer cell phagocytosis
      is alone sufficient to affect tumor immunity. Acute myeloid leukemia (AML) cells
      expressing cell-surface CRT were generated in order to characterize the
      mechanism(s) through which CRT activates tumor immune responses. Potent immune
      mediated control or rejection of AML was observed in mice with CRT-expressing
      leukemia. The "CRT effect" was ultimately T-cell dependent, but dendritic cells
      (DCs), and CD8alpha+ DCs in particular, were also necessary, indicating that CRT
      might act directly on these DCs. CRT-expressing AML cells were slightly more
      susceptible to phagocytosis by DCs in vivo, but this effect was unlikely to
      explain the potent immunity observed. CRT did not affect classical DC maturation
      markers, but induced expression of type I interferon (IFN), which was critical
      for its positive effect on survival. In conclusion, CRT functions as a "danger
      signal" that promotes a host type I IFN response associated with the induction of
      potent leukemia-specific T-cell immunity.

PMID- 28507790
TI  - CD69 is a direct HIF-1alpha target gene in hypoxia as a mechanism enhancing
      expression on tumor-infiltrating T lymphocytes.
AB  - CD69 is an early activation marker on the surface of T lymphocytes undergoing
      activation by cognate antigen. We observed intense expression of CD69 on tumor
      infiltrating T-lymphocytes that reside in the hypoxic tumor microenvironment and
      hypothesized that CD69 could be, at least partially, under the control of the
      transcriptional hypoxia response. In line with this, human and mouse CD3
      stimulated lymphocytes cultured under hypoxia (1% O2) showed increased expression
      of CD69 at the protein and mRNA level. Consistent with these findings, mouse T
      lymphocytes that had recently undergone hypoxia in vivo, as denoted by
      pimonidazole staining, were more frequently CD69+ in the tumor and bone marrow
      hypoxic tissue compartments. We found evidence for HIF-1alpha involvement both
      when using T-lymphocytes from inducible HIF-1alpha-/- mice and when observing
      tumor-infiltrating T-lymphocytes in mice whose T cells are HIF-1alpha-/-. Direct
      pro-transcriptional activity of HIF-1alpha on a newly identified hypoxia response
      element (HRE) found in the human CD69 locus was demonstrated by ChIP experiments.
      These results uncover a connection between the HIF-1alpha oxygen-sensing pathway
      and CD69 immunobiology.

PMID- 28507791
TI  - The mutational status of p53 can influence its recognition by human T-cells.
AB  - p53 was reported to be an attractive immunotherapy target because it is mutated
      in approximately half of human cancers, resulting in its inactivation and often
      accumulation in tumor cells. Peptides derived from p53 are presented by class I
      MHC molecules and may act as tumor-associated epitopes which could be targeted by
      p53-specific T cells. Interestingly, it was recently shown that there is a lack
      of significant correlation between p53 expression levels in tumors and their
      recognition by p53-TCR transduced T cells. To better understand the influence of
      the mutational status of p53 on its presentation by the MHC system and on T cell
      antitumor reactivity, we generated several mutant p53 constructs and expressed
      them in HLA-A2+/p53- cells. Upon co-culture with p53-specific T cells, we
      measured the specific recognition of p53-expressing target cells by means of
      cytokine secretion, marker upregulation and cytotoxicity, and in parallel
      determined p53 expression levels by intracellular staining. We also examined the
      relevance of antigen presentation components on p53 recognition and the impact of
      mutant p53 expression on cell-cycle dynamics. Our results show that selected p53
      mutations altering protein stability can modulate p53 presentation to T cells,
      leading to a differential immune reactivity inversely correlated with measured
      p53 protein levels. Thus, p53 may behave differently than other classical tumor
      antigens and its mutational status should therefore be taken into account when
      elaborating immunotherapy treatments of cancer patients targeting p53.

PMID- 28507792
TI  - Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects
      through T cell activation.
AB  - Combination of oncolytic virotherapy with immunomodulators is emerging as a
      promising therapeutic strategy for numerous tumor entities. In this study, we
      developed measles Schwarz vaccine strain vectors encoding immunomodulators to
      support different phases in the establishment of antitumor immune responses.
      Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent
      MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein
      (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively,
      as the most effective. Treatment of established tumors with MeVac FmIL-12
      achieved 90% complete remissions. Profiling of the tumor immune microenvironment
      revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL
      12 ensuring potent early natural killer and effector T cell activation as well as
      upregulation of the effector cytokines IFN-gamma and TNF-alpha. CD8+ T cells were
      found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of
      this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery
      and elucidate mechanisms of successful immunovirotherapy.

PMID- 28507793
TI  - Composite biomarkers defined by multiparametric immunofluorescence analysis
      identify ALK-positive adenocarcinoma as a potential target for immunotherapy.
AB  - Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for
      non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of
      the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD
      1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of
      NSCLC. Some predictive biomarkers of clinical response to this therapy are
      starting to emerge, such as PD-L1 expression by tumor/stromal cells and
      infiltration by CD8+ T cells expressing PD-1. To more effectively integrate all
      of these potential biomarkers of clinical response to immunotherapy, we have
      developed a multiparametric immunofluorescence technique with automated immune
      cell counting to comprehensively analyze the tumor microenvironment of ALK
      positive adenocarcinoma (ADC). When analyzed as either a continuous or a
      dichotomous variable, the mean number of tumor cells expressing PD-L1 (p = 0.012)
      and the percentage of tumor cells expressing PD-L1 were higher in ALK-positive
      ADC than in EGFR-mutated ADC or WT (non-EGFR-mutated and non-KRAS-mutated) NSCLC.
      A very strong correlation between PD-L1 expression on tumor cells and
      intratumoral infiltration by CD8+ T cells was observed, suggesting that an
      adaptive mechanism may partly regulate this expression. A higher frequency of
      tumors combining positive PD-L1 expression and infiltration by intratumoral CD8+
      T cells or PD-1+CD8+ T cells was also observed in ALK-positive lung cancer
      patients compared with EGFR-mutated (p = 0.03) or WT patients (p = 0.012). These
      results strongly suggest that a subgroup of ALK-positive lung cancer patients may
      constitute good candidates for anti-PD-1/-PD-L1 therapies.

PMID- 28507794
TI  - A novel nanobody-based target module for retargeting of T lymphocytes to EGFR
      expressing cancer cells via the modular UniCAR platform.
AB  - Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T
      cells underline their impressive therapeutic potential. However, once adoptively
      transferred into patients, there is little scope left to shut them down after
      elimination of tumor cells or in case adverse side effects occur. This becomes of
      special relevance if they are directed against commonly expressed tumor
      associated antigens (TAAs) such as receptors of the ErbB family. To overcome this
      limitation, we recently established a modular CAR platform technology termed
      UniCAR. UniCARs are not directed against TAAs but instead against a unique
      peptide epitope on engineered recombinant targeting modules (TMs), which guide
      them to the target. In the absence of a TM UniCAR T cells are inactive. Thus an
      interruption of any UniCAR activity requires an elimination of unbound TM and the
      TM complexed with UniCAR T cells. Elimination of the latter one requires a
      disassembly of the UniCAR-TM complexes. Here, we describe a first nanobody (nb)
      based TM directed against EGFR. The novel TM efficiently retargets UniCAR T cells
      to EGFR positive tumors and mediates highly efficient target-specific and target
      dependent tumor cell lysis both in vitro and in vivo. After radiolabeling of the
      novel TM with 64Cu and 68Ga, we analyzed its biodistribution and clearance as
      well as the stability of the UniCAR-TM complexes. As expected unbound TM is
      rapidly eliminated while the elimination of the TM complexed with UniCAR T cells
      is delayed. Nonetheless, we show that UniCAR-TM complexes dissociate in vitro and
      in vivo in a concentration-dependent manner in line with the concept of a
      repeated stop and go retargeting of tumor cells via the UniCAR technology.

PMID- 28507796
TI  - LYG1 exerts antitumor function through promoting the activation, proliferation,
      and function of CD4+ T cells.
AB  - Identification of novel stimulatory cytokines with antitumor function would have
      great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme
      G-like 1) identified through the strategy of Immunogenomics as a novel classical
      secretory protein with tumor-inhibiting function. LYG1 recombinant protein
      (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but
      not in SCID-beige mice, Rag1-/- mice, CD4+- or CD8+ T cell-deleted mice. It could
      increase the number of CD4+ and CD8+ T cells in tumor-infiltrating lymphocytes,
      tumor-draining lymph nodes, and spleens, and promote IFNgamma production by T
      cells in tumor-bearing mice. In vitro experiments demonstrated that rhLYG1 could
      directly enhance IFNgamma secretion by CD4+ T cells, but not CD8+ T cells.
      Moreover, it could promote the activation, proliferation, and IFNgamma production
      of tumor antigen-specific CD4+ T cells. The tumor-inhibiting effect of LYG1 was
      eliminated in Ifng-/- mice. Furthermore, LYG1 deficiency accelerated B16 and LLC1
      tumor growth and inhibited the function of T cells. In summary, our findings
      reveal a tumor-inhibiting role for LYG1 through promoting the activation,
      proliferation, and function of CD4+ T cells in antitumor immune responses,
      offering implications for novel tumor immunotherapy.

PMID- 28507795
TI  - Digital analysis and epigenetic regulation of the signature of rejection in
      colorectal cancer.
AB  - The immune system plays a pivotal role in the development and progression of
      colorectal cancer (CRC). Tumor immune rejection has been previously linked to the
      activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1.
      Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these
      ISG in the tumor microenvironment. In this translational study, we develop a
      digital image analysis protocol to identify the ISG-gene expression signature and
      investigate miRNA expression in the immediate environment of invading cancer
      cells. Digital immunophenotyping was performed using next generation tissue
      microarrays from 241 well-characterized CRC patients and analyzed with
      clinicopathological and molecular information. Active ISG signaling in the tumor
      stroma differentiated an immune-activated (n = 178) and a quiescent (n = 43)
      phenotype. The activated phenotype was associated with high counts of
      intratumoral CD8+ cytotoxic T-lymphocytes (CTL; p = 0.007) and expression of the
      immune effector molecules granzyme B (p < 0.001) and perforin (p = 0.020). Immune
      activated tumors also showed an elevated expression of the intercellular adhesion
      molecule-1 (ICAM-1, p = 0.006) which may facilitate CTL infiltration. Patients
      with immune-activated CRC had a considerably reduced risk of developing distant
      metastases (p = 0.001, OR = 0.034, 95%CI = 0.006-0.183). High expression of the
      immunoregulatory miR-34a and miR-93 corresponded to a 2-2.5-fold decrease of
      STAT1 (p = 0.006) and IRF-1 (p = 0.058), a feature more commonly seen in a
      quiescent microenvironment. Analysis of a combined ISG marker profile by digital
      pathology stratifies CRC patients into diametrically opposed immune phenotypes.
      Targeted inhibition of miRNAs within the tumor microenvironment may form a new
      strategy to stimulate the anti-tumoral immune response.

PMID- 28507797
TI  - IL15 induces a potent antitumor activity in NK cells isolated from malignant
      pleural effusions and overcomes the inhibitory effect of pleural fluid.
AB  - Natural Killer (NK) cells are capable of recognizing and killing cancer cells and
      play an important role in tumor immunosurveillance. However, tumor-infiltrating
      NK cells are frequently impaired in their functional capability. A remarkable
      exception is represented by NK cells isolated from malignant pleural effusions
      (PE) that are not anergic and, upon IL2-induced activation, efficiently kill
      tumor cells. Although IL2 is used in various clinical trials, severe side effects
      may occur in treated patients. In this study, we investigated whether also other
      clinical-grade cytokines could induce strong cytotoxicity in NK cells isolated
      from pleural fluid of patients with primary or metastatic tumors of different
      origins. We show that PE-NK cells, cultured for short-time intervals with IL15,
      maintain the CD56bright phenotype, a high expression of the main activating
      receptors, produce cytokines and kill tumor cells in vitro similarly to those
      treated with IL2. Moreover, IL15-activated PE-NK cells could greatly reduce the
      growth of established tumors in mice. This in vivo antitumor effect correlated
      with the ability of IL15-activated PE-NK cells to traffic from periphery to the
      tumor site. Finally, we show that IL15 can counteract the inhibitory effect of
      the tumor pleural microenvironment. Our study suggests that IL15-activated NK
      cells isolated from pleural fluid (otherwise discarded after thoracentesis) may
      represent a suitable source of effector cells to be used in adoptive
      immunotherapy of cancer.

PMID- 28507798
TI  - Tumor-infiltrating neutrophils predict benefit from adjuvant chemotherapy in
      patients with muscle invasive bladder cancer.
AB  - Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in
      tumorigenesis. The objective of this study is to assess the prognostic effect of
      TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder
      cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC
      patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the
      study. TINs were evaluated by immunohistochemical staining of CD66b or the
      CIBERSORT method. Patients with high TINs had a significantly poorer overall
      survival (p = 0.001, p < 0.001, and p = 0.002, respectively) in the three sets.
      In the multivariate analysis, the presence of high TINs (HR = 2.122, p = 0.007;
      HR = 3.807, p < 0.001; HR = 2.104, p = 0.001; respectively) was identified as an
      independent prognostic factor for overall survival in the three sets. More
      importantly, Low TINs patients had significantly longer overall survival in
      patients without ACT in the three sets. Gene set enrichment analysis showed that
      lymphocyte activation (p < 0.001) and T cell activation (p = 0.008) were
      significantly enriched in the low TINs group. In addition, TINs were negatively
      correlated with CD8+ T cells, suggesting that the status of high-TINs was linked
      to the status of immunosuppression in MIBC. TINs could be used as independent
      prognostic factor. Low TINs identified a subgroup of MIBC patients who appeared
      to benefit from adjuvant chemotherapy. Incorporation of TINs into TNM system
      could further stratify patients with different prognosis.

PMID- 28507799
TI  - Characterization of a human anti-tumoral NK cell population expanded after BCG
      treatment of leukocytes.
AB  - Immunotherapy, via intra-vesical instillations of BCG, is the therapy of choice
      for patients with high-risk non-muscle invasive bladder cancer. The subsequent
      recruitment of lymphocytes and myeloid cells, as well as the release of cytokines
      and chemokines, is believed to induce a local immune response that eliminates
      these tumors, but the detailed mechanisms of action of this therapy are not well
      understood. Here, we have studied the phenotype and function of the responding
      lymphocyte populations as well as the spectrum of cytokines and chemokines
      produced in an in vitro model of human peripheral blood mononuclear cells (PBMCs)
      co-cultured with BCG. Natural killer (NK) cell activation was a prominent feature
      of this immune response and we have studied the expansion of this lymphocyte
      population in detail. We show that, after BCG stimulation, CD56dim NK cells
      proliferate, upregulate CD56, but maintain the expression of CD16 and the ability
      to mediate ADCC. CD56bright NK cells also contribute to this expansion by
      increasing CD16 and KIR expression. These unconventional CD56bright cells
      efficiently degranulated against bladder cancer cells and the expansion of this
      population required the release of soluble factors by other immune cells in the
      context of BCG. Consistent with these in vitro data, a small, but significant
      increase in the intensity of CD16 expression was noted in peripheral blood
      CD56bright cells from bladder cancer patients undergoing BCG therapy, that was
      not observed in patients treated with mitomycin-C instillations. These
      observations suggest that activation of NK cells may be an important component of
      the anti-tumoral immune response triggered by BCG therapy in bladder cancer.

PMID- 28507800
TI  - Formyl peptide receptor 1 suppresses gastric cancer angiogenesis and growth by
      exploiting inflammation resolution pathways.
AB  - Chronic inflammation can result from inadequate engagement of resolution
      mechanisms, mainly accomplished by specialized pro-resolving mediators (SPMs)
      arising from the metabolic activity of lipoxygenases (ALOX5/15) on omega-6 or
      omega-3 essential polyunsaturated fatty acids (PUFA). We previously demonstrated
      that formyl peptide receptor 1 (FPR1) suppresses gastric cancer (GC) by
      inhibiting its inflammatory/angiogenic potential. In this study, we asked whether
      FPR1 exploits inflammation resolution pathways to suppress GC angiogenesis and
      growth. Here, we demonstrate that genetic or pharmacologic modulation of FPR1 in
      GC cells regulated ALOX5/15 expression and production of the SPMs Resolvin D1
      (RvD1) and Lipoxin B4 (LXB4). SPM treatment of GC cells abated their angiogenic
      potential. Genetic deletion of ALOX15 or of the RvD1 receptor GPR32 increased the
      angiogenic and tumorigenic activity of GC cells thereby mimicking FPR1 loss.
      Deletion/inhibition of ALOX5/15 or GPR32 blocked FPR1-mediated anti-angiogenic
      activities, indicating that ALOX5/15 and GPR32 are required for FPR1's pro
      resolving action. An omega-3- or omega-6-enriched diet enforced SPM endogenous
      production in mice and inhibited growth of shFPR1 GC xenografts by suppressing
      their angiogenic activity. These data implicate that FPR1 and/or pro-resolving
      pathway components might be used as risk/prognostic markers for GC; omega-6/3
      enriched diets, and targeting FPR1 or SPM machinery may be exploited for GC
      management.

PMID- 28507801
TI  - The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma
      and associated with PD-L1/PD-1: A future perspective for a combined gastric
      cancer therapy?
AB  - A combined blockade of V-domain Ig suppressor of T-cell activation (VISTA) and PD
      1 is a promising new cancer treatment option, which was efficient in murine tumor
      models and is currently tested in first phase I studies. Here, we analyzed the
      VISTA expression in a large and well-characterized gastric cancer (GC) cohort on
      464 therapy-naive GC samples and 14 corresponding liver metastases using
      immunohistochemistry. Staining results were correlated with clinico-pathological
      characteristics, genetic alterations and survival. VISTA expression in tumor
      cells was detected in 41 GCs (8.8%) and 2 corresponding liver metastases (14.3%).
      Moreover, VISTA expression in immune cells was observed in 388 GCs (83.6%) and 6
      liver metastases (42.9%). VISTA expression was associated with the Lauren
      phenotype, tumor localization, Epstein-Barr virus infection, KRAS- and PIK3CA
      mutational status and PD-L1 expression. There was no significant correlation with
      patient outcome. Moreover, a change of VISTA expression in immune cells during
      tumor progression was observed. The co-incidence of VISTA and PD-L1 expression
      indicates a dual immune evasion mechanism of GC tumor cells and makes GC an
      interesting target for novel combined immune checkpoint inhibitor treatments.

PMID- 28507803
TI  - PD-L1 expression on malignant cells is no prerequisite for checkpoint therapy.
AB  - Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for
      several tumor types, but the mechanism is not fully understood. PD-L1 expression
      on tumor biopsies is generally regarded as an inclusion criterion for this cancer
      therapy. Here, we describe the PD-L1-blocking therapeutic responses of
      preclinical tumors in which PD-L1 expression was removed from cancer cells, but
      not from immune infiltrate. Lack of PD-L1 expression on malignant cells delayed
      tumor outgrowth in a CD8+ T cell-mediated fashion, showing the importance of this
      molecule in immune suppression. PD-L1 expression was evident on myeloid
      infiltrating cells in the microenvironment of these tumors and targeting stromal
      PD-L1 with blocking antibody therapy had additional antitumor effect,
      demonstrating that PD-L1 on both malignant cells and immune cells is involved in
      the mechanism of immunotherapeutic antibodies. Importantly, comparable results
      were obtained with PD-1-blocking therapy. These findings have implications for
      inclusion of cancer patients in PD-1/PD-L1 blockade immunotherapies.

PMID- 28507804
TI  - HLA dependent immune escape mechanisms in B-cell lymphomas: Implications for
      immune checkpoint inhibitor therapy?
AB  - Antigen presentation by tumor cells in the context of Human Leukocyte Antigen
      (HLA) is generally considered to be a prerequisite for effective immune
      checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II
      and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical
      Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas
      (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous
      system lymphomas (PCNSL) and 19 testicular lymphomas. We describe a novel
      mechanism of immune escape in which loss of HLA-DM expression results in aberrant
      membranous invariant chain peptide (CLIP) expression in HLA class II cell surface
      positive lymphoma cells, preventing presentation of antigenic peptides. In HLA
      class II positive cases, HLA-DM expression was lost in 49% of cHL, 0% of NLPHL,
      14% of DLBCL, 3% of PCNSL and 0% of testicular lymphomas. Considering HLA class
      I, HLA class II and HLA-DM together, 88% of cHL, 10% of NLPHL, 62% of DLBCL, 77%
      of PCNSL and 87% of testicular lymphoma cases had abnormal HLA expression
      patterns. In conclusion, an HLA expression pattern incompatible with normal
      antigen presentation is common in cHL, DLBCL, PCNSL and testicular lymphoma.
      Retention of CLIP in HLA class II caused by loss of HLA-DM is a novel immune
      escape mechanism, especially prevalent in cHL. Aberrant HLA expression should be
      taken into account when evaluating efficacy of checkpoint inhibitors in B-cell
      lymphomas.

PMID- 28507802
TI  - B cells and the humoral response in melanoma: The overlooked players of the tumor
      microenvironment.
AB  - Evidence of tumor-resident mature B cell and antibody compartments and reports of
      associations with favorable prognosis in malignant melanoma suggest that humoral
      immunity could participate in antitumor defense. Likely striving to confer
      immunological protection while being subjected to tumor-promoting immune
      tolerance, B cells may engender multiple functions, including antigen processing
      and presentation, cytokine-mediated signaling, antibody class switching,
      expression and secretion. We review key evidence in support of multifaceted
      immunological mechanisms by which B cells may counter or contribute to malignant
      melanoma, and we discuss their potential translational implications. Dissecting
      the contributions of tumor-associated humoral responses can inform future
      treatment avenues.

PMID- 28507805
TI  - Generation and functional characterization of MDSC-like cells.
AB  - Myeloid-derived suppressor cells (MDSC) are critical in regulating immune
      responses by suppressing antigen presenting cells (APC) and T cells. We
      previously observed that incubation of peripheral blood monocytes with
      interleukin (IL)-10 during their differentiation to monocyte-derived dendritic
      cells (moDCs) results in the generation of an APC population with a CD14+HLA
      DRlowphenotype (IL-10-APC) with reduced stimulatory capacity similar to human
      MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to
      moDC caused a reduction of DC-induced T-cell proliferation, of the expression of
      maturation markers, and of secreted cytokines and chemokines such as TNF-alpha,
      IL-6, MIP-1alpha and Rantes. Addition of IL-10-APC increased the
      immunosuppressive molecule osteoactivin and its corresponding receptor syndecan-4
      on moDC. Moreover, CD14+HLA-DRlow MDSC isolated from healthy donors expressed
      high levels of osteoactivin, which was even further upregulated by the auxiliary
      addition of IL-10. Using transcriptome analysis, we identified a set of molecules
      and pathways mediating these effects. In addition, we found that IL-10-APC as
      well as human isolated MDSC expressed higher levels of programmed death (PD)-1,
      PD-ligand-1 (PD-L1), glucocorticoid-induced-tumor-necrosis-factor-receptor
      related-protein (GITR) and GITR-ligand. Inhibition of osteoactivin, syndecan-4,
      PD-1 or PD-L1 on MDSC by using blocking antibodies restored the stimulatory
      capacity of DC in co-incubation experiments. Activation of MDSC with Dectin-1
      ligand curdlan reduced the expression of osteoactivin and PD-L1. Our results
      demonstrate that osteoactivin/syndecan-4 and PD-/PD-L1 are key molecules that are
      profoundly involved in the inhibitory effects of MDSC on DC function and might be
      promising tools for clinical application.

PMID- 28507807
TI  - Host antitumor resistance improved by the macrophage polarization in a chimera
      model of patients with HCC.
AB  - Despite major advances in curative and palliative approaches, hepatocellular
      carcinoma (HCC) is still the third leading cause of cancer-related death
      worldwide. M1 macrophages (Mphi) play a key role in host antitumor defenses in
      HCC. In our study, CD14+ cells were isolated from the peripheral blood of four
      groups of HCC patients (group-1, patients with stage 0 HCC; group-2, patients
      with stage A HCC; group-3, patients with stage B HCC; and group-4, patients with
      stage C HCC) and characterized phenotypically. Then, CD14+ cells from group-2 and
      group-3 HCC patients were induced to polarize and tested for their antitumor
      abilities in a chimera model of HCC patients. Human HCCs (HepG2 solid tumors)
      grew in a chimera model of group-3 patients (group-3 HCC chimeras) but not in a
      chimera model of group-2 patients (group-2 HCC chimeras). In response to HCC
      antigens, the majority of CD14+ cells from group-2 patients (group-2 CD14+ cells)
      switched to the M1 phenotype (IL-12+IL-10-iNOS+cells), whereas the majority of
      CD14+ cells from group-3 patients (group-3 CD14+ cells) did not switch to the M1
      phenotype and continued to express M2b phenotypic properties (IL-12-IL
      10+CCL1+iNOS-cells). Group-3 CD14+ cells showed M1Mphi polarization after
      treatment with CCL1 antisense oligodeoxynucleotide (ODN). Therefore, our study
      indicates that anti-HCC defenses of group-3 HCC chimeras are improved after CCL1
      antisense ODN treatment.

PMID- 28507806
TI  - Preclinical efficacy of immune-checkpoint monotherapy does not recapitulate
      corresponding biomarkers-based clinical predictions in glioblastoma.
AB  - Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of
      immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs
      targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain
      GBM's intrinsic susceptibility (or resistance) toward these ICIs, through
      clinical biomarkers that may also "guide and prioritize" preclinical testing.
      Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict
      GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers,
      including mutational or predicted-neoantigen burden, pre-existing or basal levels
      of tumor-infiltrating T lymphocytes (TILs), differential expression of immune
      checkpoints within the tumor and their correlation with particular TILs/Treg
      associated functional signature and prognostic impact of differential immune
      checkpoint expression. Based on these analyses, we found that predictive
      biomarkers of ICI responsiveness exhibited inconsistent patterns in GBM patients,
      i.e., they either predicted ICI resistance (as compared with typical ICI
      responsive cancer-types like melanoma, lung cancer or bladder cancer) or
      susceptibility to therapeutic targeting of CTLA4 or IDO1. On the other hand, our
      comprehensive literature meta-analysis and preclinical testing of ICIs using an
      orthotopic GL261-glioma mice model, indicated significant antitumor properties of
      anti-PD1 antibody, whereas blockade of IDO1 or CTLA4 either failed or provided
      very marginal advantage. These trends raise the need to better assess the
      applicability of ICIs and associated biomarkers for GBM.

PMID- 28507808
TI  - Pro-necrotic molecules impact local immunosurveillance in human breast cancer.
AB  - Necrosis culminates in spilling cellular content through the permeabilized plasma
      membrane, thereby releasing potentially immunostimulatory molecules in the
      pericellular space of dead cells. Accordingly, molecules involved in necroptotic
      signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3)
      and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer
      immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro
      necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with
      immune-related metagenes in several cancer types (breast, colorectal, lung,
      ovary, melanoma), revealing the strongest associations in breast cancer. In two
      independent breast cancer cohorts, the expression of MLKL and DFNA5 was decreased
      at the mRNA levels in tumor as compared with normal tissues. Moreover, MLKL
      expression exhibited a strong positive correlation with genes reflecting the
      presence of B, NK and T lymphocytes in the tumor bed, in multiple distinct breast
      cancer subtypes. In contrast, the positive correlation between RIPK3 and lymphoid
      cells was restricted to HER2+ and triple negative/basal-like breast cancer.
      Moreover, the expression of DFNA5, which mediates post-apoptotic secondary
      necrosis, mostly correlated with the monocytic lineage and macrophages in
      ER+/luminal A breast cancers. MLKL (and to some extent RIPK1 and RIPK3) was
      strongly associated with the local expression of genes involved in interferon
      alpha and interferon-gamma responses. Altogether, these results support the idea
      that pro-necrotic signaling facilitates intratumoral immune responses in human
      breast cancer.

PMID- 28507810
TI  - TIE-2 expressing monocytes in human cancers.
AB  - Tumor-associated macrophages (TAM) are well known as a key player in the tumor
      microenvironment, which support cancer progression. More recently, a lineage of
      monocytes characterized by the expression of the TIE-2/Tek angiopoietin receptor
      identified a subset of circulating and tumor-associated monocytes endowed with
      proangiogenic activity. TIE-2 expressing monocytes (TEM) were found both in
      humans and mice. Here, we review the phenotypes and functions of TEM reported so
      far in human cancer and their potential use as markers of cancer progression and
      metastasis. Finally, we discuss the therapeutic approaches currently used or
      proposed to target TEM.

PMID- 28507809
TI  - T cell therapy targeting a public neoantigen in microsatellite instable colon
      cancer reduces in vivo tumor growth.
AB  - T-cell receptor (TCR) transfer is an attractive strategy to increase the number
      of cancer-specific T cells in adoptive cell therapy. However, recent clinical and
      pre-clinical findings indicate that careful consideration of the target antigen
      is required to limit the risk of off-target toxicity. Directing T cells against
      mutated proteins such as frequently occurring frameshift mutations may thus be a
      safer alternative to tumor-associated self-antigens. Furthermore, such frameshift
      mutations result in novel polypeptides allowing selection of TCRs from the non
      tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to
      central tolerance. The transforming growth factor beta Receptor II frameshift
      mutation (TGFbetaRIImut) is found in Lynch syndrome cancer patients and in
      approximately 15% of sporadic colorectal and gastric cancers displaying
      microsatellite instability (MSI). The -1A mutation within a stretch of 10 adenine
      bases (nucleotides 709-718) of the TGFbetaRII gene gives rise to immunogenic
      peptides previously used for vaccination of MSI+ colorectal cancer patients in a
      Phase I clinical trial. From a clinically responding patient, we isolated a
      cytotoxic T lymphocyte (CTL) clone showing a restriction for HLA-A2 in complex
      with TGFbetaRIImut peptide. Its TCR was identified and shown to redirect T cells
      against colon carcinoma cell lines harboring the frameshift mutation. Finally, T
      cells transduced with the HLA-A2-restricted TGFbetaRIImut-specific TCR were
      demonstrated to significantly reduce the growth of colorectal cancer and enhance
      survival in a NOD/SCID xenograft mouse model.

PMID- 28507811
TI  - Adoptive natural killer cell therapy is effective in reducing pulmonary
      metastasis of Ewing sarcoma.
AB  - The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains
      dismal despite intensification of combination chemotherapy and radiotherapy,
      precipitating the need for novel alternative therapies with minimal side effects.
      Natural killer (NK) cells are promising additions to the field of cellular
      immunotherapy. Adoptive NK cell therapy has shown encouraging results in
      hematological malignancies. Despite these initial promising successes, however,
      NK cell therapy for solid tumors remains to be investigated using in vivo tumor
      models. The purpose of this study is to evaluate the efficacy of ex vivo expanded
      human NK cells in controlling primary and metastatic ES tumor growth in vitro and
      in vivo. Using membrane-bound IL-21 containing K562 (K562-mbIL-21) expansion
      platform, we were able to obtain sufficient numbers of expanded NK (eNK) cells
      that display favorable activation phenotypes and inflammatory cytokine secretion,
      along with a strong in vitro cytotoxic effect against ES. Furthermore, eNK
      therapy significantly decreased lung metastasis without any significant
      therapeutic effect in limiting primary tumor growth in an in vivo xenograft
      model. Our data demonstrate that eNK may be effective against pulmonary
      metastatic ES, but challenges remain to direct proper trafficking and augmenting
      the cytotoxic function of eNK to target primary tumor sites.

PMID- 28507812
TI  - A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV
      related tumors.
AB  - The use of monoclonal antibodies (mAb) for the diagnosis and treatment of
      malignancies is acquiring an increasing clinical importance, thanks to their
      specificity, efficacy and relative easiness of use. However, in the context of
      Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can
      benefit from therapeutic mAb targeting specific B-cell lineage antigens. To
      overcome this limitation, we generated a new mAb specific for BARF1, an EBV
      encoded protein with transforming and immune-modulating properties. BARF1 is
      expressed as a latent protein in nasopharyngeal (NPC) and gastric carcinoma (GC),
      and also in neoplastic B cells mainly upon lytic cycle induction, thus
      representing a potential target for all EBV-related malignancies. Considering
      that BARF1 is largely but not exclusively secreted, the BARF1 mAb was selected on
      the basis of its ability to bind a domain of the protein retained at the cell
      surface of tumor cells. In vitro, the newly generated mAb recognized the target
      molecule in its native conformation, and was highly effective in mediating both
      ADCC and CDC against BARF1-positive tumor cells. In vivo, biodistribution
      analysis in mice engrafted with BARF1-positive and -negative tumor cells
      confirmed its high specificity for the target. More importantly, the mAb
      disclosed a relevant antitumor potential in preclinical models of NPC and
      lymphoma, as evaluated in terms of both reduction of tumor masses and long-term
      survival. Taken together, these data not only confirm BARF1 as a promising target
      for immunotherapeutic interventions, but also pave the way for a successful
      translation of this new mAb to the clinical use.

PMID- 28507814
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1080/2162402X.2016.1249558.].

PMID- 28507813
TI  - Deep exploration of the immune infiltrate and outcome prediction in testicular
      cancer by quantitative multiplexed immunohistochemistry and gene expression
      profiling.
AB  - Platinum-based chemotherapy is usually curative for patients with testicular germ
      cell tumors (TGCT), but a subset of patients experience disease progression and
      poor clinical outcomes. Here, we tested whether immune profiling of TGCT could
      identify novel prognostic markers and therapeutic targets for this patient
      cohort. We obtained primary and metastatic TGCT samples from one center. We
      performed immune profiling using multiplexed fluorescence immunohistochemistry
      (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression
      profiling (Nanostring nCounter Immune panel). Publically available data sets were
      used to validate primary sample analyses. Nearly all samples had some degree of T
      cell infiltration and immune checkpoint expression. Seminomas were associated
      with increased CD3+ T-cell infiltration, decreased Regulatory T-cells, increased
      PD-L1, and increased PD-1/PD-L1 spatial interaction compared with non-seminomas
      using FIHC. Gene expression profiling confirmed these findings and also
      demonstrated increased expression of T-cell markers (e.g., IFNgamma, and LAG3)
      and cancer/testis antigens (e.g., PRAME) in seminomas, whereas non-seminomas
      demonstrated high neutrophil and macrophage gene signatures. Irrespective of
      histology, advanced TGCT stage was associated with decreased T-cell and NK-cell
      signatures, while Treg, neutrophil, mast cell and macrophage signatures increased
      with advanced stage. Importantly, cancer/testis antigen, neutrophil, and
      CD8+/regulatory T-cell signatures correlated with recurrence free survival. Thus,
      deep immune characterization of TGCT using IHC and gene expression profiling
      identified activated T-cell infiltration which correlated with seminoma histology
      and good prognosis. These results may provide a rationale for testing of anti-PD
      1/PD-L1 agents and suggest prognostic markers.

PMID- 28507815
TI  - A new molecular diagnostic tool for surveying and monitoring Triops cancriformis
      populations.
AB  - The tadpole shrimp, Triops cancriformis, is a freshwater crustacean listed as
      endangered in the UK and Europe living in ephemeral pools. Populations are
      threatened by habitat destruction due to land development for agriculture and
      increased urbanisation. Despite this, there is a lack of efficient methods for
      discovering and monitoring populations. Established macroinvertebrate monitoring
      methods, such as net sampling, are unsuitable given the organism's life history,
      that include long lived diapausing eggs, benthic habits and ephemerally active
      populations. Conventional hatching methods, such as sediment incubation, are both
      time consuming and potentially confounded by bet-hedging hatching strategies of
      diapausing eggs. Here we develop a new molecular diagnostic method to detect
      viable egg banks of T. cancriformis, and compare its performance to two
      conventional monitoring methods involving diapausing egg hatching. We apply this
      method to a collection of pond sediments from the Wildfowl & Wetlands Trust
      Caerlaverock National Nature Reserve, which holds one of the two remaining
      British populations of T. cancriformis. DNA barcoding of isolated eggs, using
      newly designed species-specific primers for a large region of mtDNA, was used to
      estimate egg viability. These estimates were compared to those obtained by the
      conventional methods of sediment and isolation hatching. Our method outperformed
      the conventional methods, revealing six ponds holding viable T. cancriformis
      diapausing egg banks in Caerlaverock. Additionally, designed species-specific
      primers for a short region of mtDNA identified degraded, inviable eggs and were
      used to ascertain the levels of recent mortality within an egg bank. Together
      with efficient sugar flotation techniques to extract eggs from sediment samples,
      our molecular method proved to be a faster and more powerful alternative for
      assessing the viability and condition of T. cancriformis diapausing egg banks.

PMID- 28507816
TI  - Psychophysical measurements in children: challenges, pitfalls, and
      considerations.
AB  - Measuring sensory sensitivity is important in studying development and
      developmental disorders. However, with children, there is a need to balance
      reliable but lengthy sensory tasks with the child's ability to maintain
      motivation and vigilance. We used simulations to explore the problems associated
      with shortening adaptive psychophysical procedures, and suggest how these
      problems might be addressed. We quantify how adaptive procedures with too few
      reversals can over-estimate thresholds, introduce substantial measurement error,
      and make estimates of individual thresholds less reliable. The associated
      measurement error also obscures group differences. Adaptive procedures with
      children should therefore use as many reversals as possible, to reduce the
      effects of both Type 1 and Type 2 errors. Differences in response consistency,
      resulting from lapses in attention, further increase the over-estimation of
      threshold. Comparisons between data from individuals who may differ in lapse rate
      are therefore problematic, but measures to estimate and account for lapse rates
      in analyses may mitigate this problem.

PMID- 28507817
TI  - Which psychological, social and physical environmental characteristics predict
      changes in physical activity and sedentary behaviors during early retirement? A
      longitudinal study.
AB  - BACKGROUND: In the context of healthy ageing, it is necessary to identify
      opportunities to implement health interventions in order to develop an active
      lifestyle with sufficient physical activity and limited sedentary time in middle
      aged and older adults. The transition to retirement is such an opportunity, as
      individuals tend to establish new routines at the start of retirement. Before
      health interventions can be developed, the psychological, social and physical
      environmental determinants of physical activity and sedentary behaviors during
      early retirement should be identified, ideally with longitudinal studies. The aim
      of this paper was first to examine whether psychological, social and physical
      environmental factors at the start of retirement predict longitudinal changes in
      physical activity and sedentary behaviors during the first years of retirement.
      Second, moderating effects of gender and educational levels were examined.
      METHODS: This longitudinal study was conducted in Flanders, Belgium. In total,
      180 recently retired (>1 month, <2 years at baseline) adults completed a postal
      questionnaire twice (in 2012-2013 and two years later in 2014-2015). The
      validated questionnaire assessed socio-demographic information, physical
      activity, sedentary behaviors, and psychological, social and physical
      environmental characteristics. Multiple moderated hierarchic regression analyses
      were conducted in SPSS 22.0. RESULTS: Higher perceived residential density (p <
      0.001) and lower aesthetics (p = 0.08) predicted an increase in active
      transportation (adjusted R2 = 0.18). Higher baseline self-efficacy was associated
      with an increase in leisure-time physical activity (p = 0.001, adjusted R2 =
      0.13). A more positive perception of old age (p = 0.04) and perceiving less
      street connectivity (p = 0.001) were associated with an increase in screen time
      (adjusted R2 = 0.06). Finally, higher baseline levels of modeling from friends (p
      = 0.06) and lower perceived land use mix access (p = 0.09) predicted an increase
      in car use (adjusted R2 = 0.06). A few moderating effects, mainly of educational
      level, were found. DISCUSSION: Walkability characteristics (perceived residential
      density) and self-efficacy at the start of retirement are the most important
      predictors of longitudinal changes in active transportation and leisure-time
      physical activity. Few moderating effects were found, so health interventions at
      the start of retirement focusing on self-efficacy and specific walkability
      characteristics could be effective to increase physical activity in recently
      retired adults. No firm conclusions can be drawn on the importance of the
      examined predictors to explain change in car use and screen time, possibly other
      factors like the home environment, or automatic processes and habit strength are
      more important to explain sedentary behaviors.

PMID- 28507819
TI  - Radix Stellariae extract prevents high-fat-diet-induced obesity in C57BL/6 mice
      by accelerating energy metabolism.
AB  - Stellaria dichotoma L. is widely distributed in Ningxia and surrounding areas in
      northwestern China. Its root, Radix Stellariae (RS), has been used in herbal
      formulae for treating asthenic-fever, infection, malaria, dyspepsia in children
      and several other symptoms. This study investigated whether the RS extract (RSE)
      alleviates metabolic disorders. The results indicated that RSE significantly
      inhibited body weight gain in high-fat (HF)-diet-fed C57BL/6 mice, reduced
      fasting glucose levels, and improved insulin tolerance. Moreover, RSE increased
      the body temperature of the mice and the expression of uncoupling proteins and
      peroxisome proliferator-activated receptors in the white adipose tissue. Thus,
      RSE alleviated metabolic disorders in HF-diet-fed C57BL/6 mice by potentially
      activating UCP and PPAR signaling.

PMID- 28507818
TI  - Screening of a natural compound library identifies emodin, a natural compound
      from Rheum palmatum Linn that inhibits DPP4.
AB  - Historically, Chinese herbal medicines have been widely used in the treatment of
      hyperglycemia, but the mechanisms underlying their effectiveness remain largely
      unknown. Here, we screened a compound library primarily comprised of natural
      compounds extracted from herbs and marine organisms. The results showed that
      emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with
      an in vitro IC50 of 5.76 uM without inhibiting either DPP8 or DPP9. A docking
      model revealed that emodin binds to DPP4 protein through Glu205 and Glu206,
      although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.)
      in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study
      suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic
      for the treatment of type 2 diabetes.

PMID- 28507821
TI  - The density and biomass of mesozooplankton and ichthyoplankton in the Negro and
      the Amazon Rivers during the rainy season: the ecological importance of the
      confluence boundary.
AB  - The boundary zone between two different hydrological regimes is often a
      biologically enriched environment with distinct planktonic communities. In the
      center of the Amazon River basin, muddy white water of the Amazon River meets
      with black water of the Negro River, creating a conspicuous visible boundary
      spanning over 10 km along the Amazon River. Here, we tested the hypothesis that
      the confluence boundary between the white and black water rivers concentrates
      prey and is used as a feeding habitat for consumers by investigating the density,
      biomass and distribution of mesozooplankton and ichthyoplankton communities
      across the two rivers during the rainy season. Our results show that mean
      mesozooplankton density (2,730 inds. m-3) and biomass (4.8 mg m-3) were higher in
      the black-water river compared to the white-water river (959 inds. m-3; 2.4 mg m
      3); however an exceptionally high mesozooplankton density was not observed in the
      confluence boundary. Nonetheless we found the highest density of ichthyoplankton
      in the confluence boundary (9.7 inds. m-3), being up to 9-fold higher than in
      adjacent rivers. The confluence between white and black waters is sandwiched by
      both environments with low (white water) and high (black water) zooplankton
      concentrations and by both environments with low (white water) and high (black
      water) predation pressures for fish larvae, and may function as a boundary layer
      that offers benefits of both high prey concentrations and low predation risk.
      This forms a plausible explanation for the high density of ichthyoplankton in the
      confluence zone of black and white water rivers.

PMID- 28507820
TI  - Self-centeredness and selflessness: happiness correlates and mediating
      psychological processes.
AB  - The main objective of this research was to test central assumptions from the Self
      centeredness/Selflessness Happiness Model. According to this model, while self
      centered psychological functioning induces fluctuating happiness, authentic
      durable happiness results from selflessness. Distinct mediating processes are
      supposed to account for these relationships: afflictive affects (e.g., anger,
      fear, jealousy, frustration) in the case of the former, and both emotional
      stability and feelings of harmony in the case of the latter. We tested these
      hypotheses in two studies based on heterogeneous samples of citizens (n = 547).
      Factor analyses revealed that self-centeredness (assessed through egocentrism and
      materialism) and selflessness (assessed through self-transcendence and
      connectedness to other) were two distinct psychological constructs. Second, while
      self-centeredness was positively and significantly related to fluctuating
      happiness, selflessness was positively and significantly related to authentic
      durable happiness. Finally, distinct psychological processes mediated these
      relationships (study 2). On one hand, the relationship between self-centeredness
      and fluctuating happiness was fully mediated by afflictive affects. On the other
      hand, emotional stability and the feeling of being in harmony partially mediated
      the relation between selflessness and authentic-durable happiness.

PMID- 28507822
TI  - Estimating the effect of burrowing shrimp on deep-sea sediment community oxygen
      consumption.
AB  - Sediment community oxygen consumption (SCOC) is a proxy for organic matter
      processing and thus provides a useful proxy of benthic ecosystem function. Oxygen
      uptake in deep-sea sediments is mainly driven by bacteria, and the direct
      contribution of benthic macro- and mega-infauna respiration is thought to be
      relatively modest. However, the main contribution of infaunal organisms to
      benthic respiration, particularly large burrowing organisms, is likely to be
      indirect and mainly driven by processes such as feeding and bioturbation that
      stimulate bacterial metabolism and promote the chemical oxidation of reduced
      solutes. Here, we estimate the direct and indirect contributions of burrowing
      shrimp (Eucalastacus cf. torbeni) to sediment community oxygen consumption based
      on incubations of sediment cores from 490 m depth on the continental slope of New
      Zealand. Results indicate that the presence of one shrimp in the sediment is
      responsible for an oxygen uptake rate of about 40 umol d-1, only 1% of which is
      estimated to be due to shrimp respiration. We estimate that the presence of ten
      burrowing shrimp m-2 of seabed would lead to an oxygen uptake comparable to
      current estimates of macro-infaunal community respiration on Chatham Rise based
      on allometric equations, and would increase total sediment community oxygen
      uptake by 14% compared to sediment without shrimp. Our findings suggest that
      oxygen consumption mediated by burrowing shrimp may be substantial in continental
      slope ecosystems.

PMID- 28507823
TI  - Cells tile a flat plane by controlling geometries during morphogenesis of Pyropia
      thalli.
AB  - BACKGROUND: Pyropia haitanensis thalli, which are made of a single layer of
      polygonal cells, are a perfect model for studying the morphogenesis of multi
      celled organisms because their cell proliferation process is an excellent example
      of the manner in which cells control their geometry to create a two-dimensional
      plane. METHODS: Cellular geometries of thalli at different stages of growth
      revealed by light microscope analysis. RESULTS: This study showed the cell
      division transect the middle of the selected paired-sides to divide the cell into
      two equal portions, thus resulting in cell sides >=4 and keeping the average
      number of cell sides at approximately six even as the thallus continued to grow,
      such that more than 90% of the cells in thalli longer than 0.08 cm had 5-7 sides.
      However, cell division could not fully explain the distributions of intracellular
      angles. Results showed that cell-division-associated fast reorientation of cell
      sides and cell divisions together caused 60% of the inner angles of cells from
      longer thalli to range from 100-140 degrees . These results indicate that cells
      prefer to form regular polygons. CONCLUSIONS: This study suggests that
      appropriate cell-packing geometries maintained by cell division and reorientation
      of cell walls can keep the cells bordering each other closely, without gaps.

PMID- 28507824
TI  - Non-Invasive Radiofrequency Field Treatment to Produce Hepatic Hyperthermia:
      Efficacy and Safety in Swine.
AB  - The Kanzius non-invasive radio-frequency hyperthermia system (KNiRFH) has been
      investigated as a treatment option for hepatic hyperthermia cancer therapy. The
      treatment involves exposing the patient to an external high-power RF (13.56 MHz)
      electric field, whereby the propagating waves penetrate deep into the tumor
      causing targeted heating based on differential tissue dielectric properties.
      However, a comprehensive examination of the Kanzius system alongside any
      associated toxicities and its ability to induce hepatic hyperthermia in larger
      animal models, such as swine, are the subjects of the work herein. Ten Yucatan
      female mini-swine were treated with the KNiRFH system. Two of the pigs were
      treated a total of 17 times over a five-week period to evaluate short- and long
      term KNiRFH-associated toxicities. The remaining eight pigs were subjected to
      single exposure sessions to evaluate heating efficacy in liver tissue. Our goal
      was to achieve a liver target temperature of 43 degrees C and to evaluate
      toxicities and burns post-treatment. Potential toxicities were evaluated by
      contrast-enhanced MRI of the upper abdomen and blood work, including complete
      metabolic panel, complete blood count, and liver enzymes. The permittivities of
      subcutaneous fat and liver were also measured, which were used to calculate
      tissue specific absorption rates (SAR). Our results indicate negligible KNiRFH
      associated toxicities; however, due to fat overheating, liver tissue temperature
      did not exceed 38.5 degrees C. This experimental limitation was corroborated by
      tissue permittivity and SAR calculations of subcutaneous fat and liver.
      Significant steps must be taken to either reduce subcutaneous fat heating or
      increase localized heating, potentially through the use of KNiRFH-active
      nanomaterials, such as gold nanoparticles or single-walled carbon nanotubes,
      which have previously shown promising results in murine cancer models.

PMID- 28507825
TI  - Spatiotemporal Strategies for Joint Segmentation and Motion Tracking From Cardiac
      Image Sequences.
AB  - Although accurate and robust estimations of the deforming cardiac geometry and
      kinematics from cine tomographic medical image sequences remain a technical
      challenge, they have significant clinical value. Traditionally, boundary or
      volumetric segmentation and motion estimation problems are considered as two
      sequential steps, even though the order of these processes can be different. In
      this paper, we present an integrated, spatiotemporal strategy for the
      simultaneous joint recovery of these two ill-posed problems. We use a mesh-free
      Galerkin formulation as the representation and computation platform, and adopt
      iterative procedures to solve the governing equations. Specifically, for each
      nodal point, the external driving forces are individually constructed through the
      integration of data-driven edginess measures, prior spatial distributions of
      myocardial tissues, temporal coherence of image-derived salient features,
      imaging/image-derived Eulerian velocity information, and cyclic motion model of
      myocardial behavior. The proposed strategy is accurate and very promising
      application results are shown from synthetic data, magnetic resonance (MR) phase
      contrast, tagging image sequences, and gradient echo cine MR image sequences.

PMID- 28507826
TI  - Near-Infrared Imaging for Detecting Caries and Structural Deformities in Teeth.
AB  - 2-D radiographs, while commonly used for evaluating sub-surface hard structures
      of teeth, have low sensitivity for early caries lesions, particularly those on
      tooth occlusal surfaces. Radiographs are also frequently refused by patients over
      safety concerns. Translucency of teeth in the near-infrared (NIR) range offers a
      non-ionizing and safe approach to detect dental caries. We report the
      construction of an NIR (850 nm) LED imaging system, comprised of an NIR source
      and an intraoral camera for rapid dental evaluations. The NIR system was used to
      image teeth of ten consenting human subjects and successfully detected secondary,
      amalgam-occluded and early caries lesions without supplementary image processing.
      The camera-wand system was also capable of revealing demineralized areas, deep
      and superficial cracks, and other clinical features of teeth usually visualized
      by X-rays. The NIR system's clinical utility, simplistic design, low cost, and
      user friendliness make it an effective dental caries screening technology in
      conjunction or in place of radiographs.

PMID- 28507827
TI  - Wearable Improved Vision System for Color Vision Deficiency Correction.
AB  - Color vision deficiency (CVD) is an extremely frequent vision impairment that
      compromises the ability to recognize colors. In order to improve color vision in
      a subject with CVD, we designed and developed a wearable improved vision system
      based on an augmented reality device. The system was validated in a clinical
      pilot study on 24 subjects with CVD (18 males and 6 females, aged 37.4 +/- 14.2
      years). The primary outcome was the improvement in the Ishihara Vision Test score
      with the correction proposed by our system. The Ishihara test score significantly
      improved ([Formula: see text]) from 5.8 +/- 3.0 without correction to 14.8 +/-
      5.0 with correction. Almost all patients showed an improvement in color vision,
      as shown by the increased test scores. Moreover, with our system, 12 subjects
      (50%) passed the vision color test as normal vision subjects. The development and
      preliminary validation of the proposed platform confirm that a wearable augmented
      reality device could be an effective aid to improve color vision in subjects with
      CVD.

PMID- 28507828
TI  - Multiple Large Perineural (Tarlov) Cysts in the Sacrum of a Cadaver: A Case
      Report and Review.
AB  - Tarlov or perineural cysts are cerebrospinal fluid (CSF)-filled sacs found
      between the perineurium and epineurium of the nerve roots. It is still unsure
      whether the origin of these cysts is intradural or extradural. They can either be
      asymptomatic or create a variety of negative impacts on comfort and quality of
      life. In this case report, we describe the presentation of multiple Tarlov cysts
      including one large cyst discovered during a routine cadaveric spinal dissection
      and the relevant and related literature. To our knowledge, this is the only
      cadaveric case report of Tarlov cysts and offers an interesting window into their
      anatomy.

PMID- 28507829
TI  - Bupropion-Induced Acute Dystonia with Dose Escalation and Use of Naranjo
      Nomogram.
AB  - Acute drug-induced dystonia is commonly associated with antipsychotic drugs,
      antidepressants, antiemetics, and other medications. Bupropion (Wellbutrin and
      Zyban) is one of the most frequently prescribed antidepressants in the United
      States and Canada and smoking cessation aid. However, only few reported cases
      have been published of acute dystonia including dystonia after discontinuation of
      bupropion and even after a single dose of bupropion. Here, we report another case
      concerning an acute dystonia resulting from bupropion after dose escalation. To
      further assess this association, we used the Naranjo nomogram, which is a
      questionnaire designed for determining the likelihood of whether an adverse drug
      reaction is actually due to the drug rather than the result of other factors. Our
      patient's total score was seven, suggesting that our patient had probable adverse
      drug reaction. In summary, our case is that selected patients may experience dose
      related acute dystonia as adverse reactions to bupropion sustained release (SR).
      Since it is one of the most commonly prescribed antidepressants and smoking
      cessation aids, clinicians should be aware of the potential dystonia associated
      with bupropion.

PMID- 28507831
TI  - Streptococcus Gordonii Empyema: A Case Report and Review of Empyema.
AB  - Streptococcus gordonii (S. gordonii) is a pioneer oral bacteria that is
      recognized as an agent of bacterial endocarditis. However, an extensive review of
      the literature revealed no reported case of S. gordonii causing empyema. We
      present a case of a 65-year-old male who presented with respiratory distress.
      Physical examination revealed several dental caries with decreased breath sounds
      in the bibasilar regions. A computed tomography (CT) scan of the chest and
      abdomen demonstrated left-sided pleural effusion and a 4.3 cm x 2.8 cm splenic
      abscess. He received intravenous (IV) antibiotics, and his blood cultures
      remained negative. Drainage of the splenic abscess grew S. gordonii. A CT-guided
      thoracentesis yielded 450 ml of exudative fluid. Pleural fluid cultures grew S.
      gordonii. A CT scan of the head and neck ruled out an intra-oral abscess. He
      received six weeks of IV penicillin with a follow-up CT scan showing resolution
      of both the splenic abscess and the left parapneumonic effusion.

PMID- 28507830
TI  - Dermatitis Due to Paederus Colombinus: Report of an Epidemic Outbreak of 68 Cases
      in the Province of Darien, Panama.
AB  - INTRODUCTION: Contact dermatitis due to Paederus is a particular form of accident
      by animal contact. It is characterized by the sudden onset of erythematous and
      vesicular lesions with burning sensation on exposed areas of the body. The aim of
      this study was to describe the epidemiological and clinical findings of an
      outbreak of Paederus dermatitis in Panama. METHODS: Clinical and epidemiological
      findings of an outbreak of contact dermatitis caused by Paederus sp. in the
      province of Darien in eastern Panama is reported. After reviewing the clinical
      records, a clinical-epidemiological questionnaire was developed and used in 20
      communities where reported cases were found. We captured and collected the
      specimens for species characterization for three consecutive days using three
      different methods of capture. RESULTS: During May-July, 2014, 68 cases of
      Paederus irritant contact dermatitis occurred in 20 communities of the Darien.
      Fifty-three percent were females. The age group of zero to five years had the
      highest number of cases, 15 (22%). The most common clinical presentation was the
      classical linear dermatitis (58%); 42% of the subjects had mirror image lesions,
      multiple vesicular-pustular lesions, and crust lesions. Symptoms were most
      commonly reported as a burning sensation (65%), followed by pruritus in 60%, pain
      (25%), and fever (nine percent). A total of 81 specimens of Paederus were
      collected, 68% in peridomiciliary areas. CONCLUSIONS: This Paederus sp.
      dermatitis report represents one of the largest outbreak described in Latin
      America and the diagnosis could be confused with others skin diseases like
      pyodermitis or other contact dermatitis.

PMID- 28507832
TI  - Disseminated Nocardia Farcinica Pneumonia with Left Adrenal Gland Abscess.
AB  - Adrenal masses pose a diagnostic challenge. The differential diagnosis includes
      functional adrenal tumors, incidentally found adrenal masses, metastases from an
      unknown primary cancer, and abscesses. Infrequently, adrenal gland abscesses have
      been reported in disseminated nocardiosis affecting immunocompetent and
      immunocompromised patients. We report a case of disseminated Nocardia farcinica
      pneumonia with an adrenal gland abscess in an immunocompetent patient with no
      identified risk factors for nocardiosis.

PMID- 28507833
TI  - Does Hemodynamic-Guided Heart Failure Management Reduce Hospitalization? A
      Systematic Review.
AB  - Heart failure (HF) is a pressing health concern as the expense of hospitalization
      financially burdens the health care system. Hemodynamic monitoring has the
      potential to detect increases in intracardiac filling pressures weeks before
      clinical deterioration; hence, preliminary findings of volume overload with the
      use of these devices may prevent the progression of disease and lead to a
      reduction in HF-associated hospitalizations. We extensively searched PubMed, Ovid
      SP, Embase, and Cochrane databases to identify all the possible studies that
      assess the effect of hemodynamic monitoring on hospitalizations in HF patients.
      The main outcomes considered were the rate of HF hospitalization, mortality,
      quality of life, and improvement in New York Heart Association (NYHA) functional
      class in the monitored group. Seven studies met all the eligibility criteria and
      were incorporated in our systematic review. Out of the seven studies we reviewed,
      three studies inserted the sensor in the pulmonary artery, three in the right
      ventricle, and only one in the left atrium. On an average, the single study on
      the left atrium showed the highest reduction (59.0%) in HF hospitalization
      followed by the pulmonary artery (56.3%) and right ventricle (31.0%),
      respectively. Our systematic review demonstrates that the use of hemodynamic
      sensors in HF patients helps to reduce HF-related hospitalizations. Therefore, a
      combination of outpatient monitoring via the use of hemodynamic sensors and fluid
      management is needed to reduce HF hospitalizations and improve outcomes in HF
      patients.

PMID- 28507834
TI  - Clinical and Radiological Improvement Following Ozone Disc Nucleolysis: A Case
      Report.
AB  - The results of traditional open surgery for herniated intervertebral disc are
      often limited by complications and failed back surgery syndrome (FBSS). Over the
      past few decades, a considerable amount of research has been done in the field of
      minimally invasive procedures as a treatment option for herniated intervertebral
      disc disease. Ozone disc nucleolysis is one such procedure which has results
      equal to or better than traditional surgery with virtually no complications. A 27
      year-old post-partum female presented to the clinic with acute onset of severe
      lower back pain radiating to the left lower limb for one month. The pain started
      suddenly during labor and gradually increased over a period of few weeks post
      partum. A magnetic resonance imaging (MRI) scan showed a large herniated disc
      bulge at the L4-L5 level causing severe radiculopathy. There was no bladder or
      bowel involvement. The patient was managed conservatively for three weeks.
      However, she failed to show any signs of improvement. She opted to undergo ozone
      disc nucleolysis under local anaesthesia. She showed significant improvement
      immediately after the procedure and there was further improvement in symptoms
      over a period of six weeks. Post-procedure follow-up at three months and six
      months showed significant improvement on the visual analogue scale (VAS), which
      was used to measure pain intensity and pain affect, along with the Oswestry
      Disability Index (ODI), which was used to measure the degree of disability due to
      the lower back pain. Her VAS score improved from nine to two at three months and
      finally to one at six months, whereas the ODI score improved significantly from
      46 to 10 at three months and eventually to four at six months. Ozone disc
      nucleolysis is an efficacious, safe, durable, and cost-effective treatment option
      for mild to moderate cases of herniated intervertebral disc which are resistant
      to conservative management. However, randomized control trials are required to
      build a long-term database regarding the efficacy and durability of ozone disc
      nucleolysis as compared to other minimally invasive procedures and surgery. We
      strongly believe that the availability of long-term data on ozone disc
      nucleolysis would make it a more acceptable form of treatment for disc herniation
      as compared to traditional surgery.

PMID- 28507835
TI  - Endoscopic View of Gastroduodenal Artery Coils at the Base of Duodenal Ulcer in
      Case of Recurrent Massive Upper Gastrointestinal Bleed.
AB  - Helicobacter pylori (H. pylori) infection is one of the major causes of bleeding
      peptic ulcer disease, which is associated with serious complications; therefore,
      the eradication of H. pylori is essential to prevent these devastating
      complications. Post-treatment follow-up is crucial to guarantee the eradication
      of the organism and may be conducted via the urea breath test, the stool antigen
      test, or a gastric biopsy. Acute massive upper gastrointestinal (UGI) bleeding is
      one of the most common complications of peptic ulcer disease. Aggressive
      treatment with early endoscopic hemostasis is essential for a favorable outcome.
      Recurrent massive nonvariceal UGI bleeding remains a challenge. Optimal
      management requires a multidisciplinary team of skilled endoscopists,
      intensivists, experienced UGI surgeons, and interventional radiologists.
      Endoscopy is the first-line treatment after hemodynamic stability is achieved.
      The role of early elective surgery or angiographic embolization in selected high
      risk patients to prevent re-bleeding remains controversial.

PMID- 28507836
TI  - Microsurgical Removal of Microcatheter in the Middle Cerebral Artery During
      Resection of an Arteriovenous Malformation Resection.
AB  - Surgical resection is the current standard of therapy for the treatment of
      arteriovenous malformation (AVM). Endovascular embolization is commonly used as
      an adjunct prior to surgical resection because it is believed to reduce the risk
      of intraoperative bleeding. Embolization has been associated with other
      complications including visual deficits, vessel perforation, and catheter
      adhesion. Catheter adhesion in which retained segments are contained within the
      embolization cast are not necessarily cause for concern, but retention of larger
      portions may confer an increased risk of thrombus formation. Such cases warrant
      the removal of the retained segments or the patient may suffer serious
      complications including death related to cerebrovascular events. In this case
      report, we describe a unique case of catheter adhesion in which the extension of
      the feeding catheter and the length of the introducer was left in its entirety
      down to the entry portion at the level of the groin and later retrieved in its
      entirety by craniotomy.

PMID- 28507837
TI  - Non-Alcoholic Fatty Liver Disease Association with Cardiac Arrhythmias.
AB  - Non-alcoholic fatty liver disease (NAFLD) has become a public health burden all
      over the world. A significant percentage of the patients with NAFLD have a co
      existing metabolic syndrome that is a risk factor for cardiovascular disease.
      Clinical as well as epidemiological research shows that NAFLD is not simply
      related to liver-related morbidity and mortality but is also associated with an
      elevated risk of coronary heart disease (CHD), irregularities of cardiac function
      as well as cardiac structure, valvular heart disease, and arrhythmias. Animal
      studies suggest that NAFLD by itself exacerbates systemic/hepatic insulin
      resistance, leads to atherogenic dyslipidemia and generates a number of pro
      inflammatory, pro-coagulant and profibrogenic mediators which play an essential
      role in the pathophysiology of cardiac abnormalities including arrhythmias.
      Hence, it is suggested that the patients with NAFLD may derive benefit from
      intensive monitoring and treatment methods to reduce the risk of CHD along with
      other cardiac/arrhythmic complications. The intent of this clinical review is to
      sum up the quickly increasing body of evidence that provides support for a robust
      relationship between NAFLD and cardiac arrhythmias and to present the putative
      biological mechanisms underlying this correlation.

PMID- 28507838
TI  - Recurrent Stress Cardiomyopathy During COPD Exacerbation: Are Beta-adrenergic
      Agonists Only to Blame?
AB  - Takotsubo cardiomyopathy (TCM) is a variant of stress-induced cardiomyopathy,
      characterized by transient left ventricular dysfunction that may be associated
      with emotional or physical triggers. We present the case of a 51-year-old
      Caucasian female with severe chronic obstructive pulmonary disease (COPD) who
      presented with syncope and was found to have her second lifetime episode of
      stress-induced cardiomyopathy. Eight months prior, she had been admitted with a
      COPD exacerbation and was found to have left ventricular (LV) dysfunction with
      ejection fraction (EF) of 22% attributed to TCM with subsequent normalization of
      her left ventricular function. Recurrence of stress-induced cardiomyopathy
      associated with COPD is a rare phenomenon and its presentation raises the
      possibility of a common underlying mechanism.

PMID- 28507839
TI  - Issues in Managing Hurthle Cell Carcinoma of Thyroid: A Case Report.
AB  - A 61-year-old woman noticed a right neck lump in October 2001. Fine needle
      aspiration showed follicular neoplasm, adenoma versus carcinoma. The ultrasound
      scan showed a solid mass of maximum dimension of 3.7 cm. She had a right thyroid
      lobectomy and isthmectomy in January 2002 (first surgery). The tissue specimen
      showed a 4.5 cm Hurthle cell carcinoma (HCC) with vascular invasion. There were
      no capsular invasion, extra-thyroidal extension, or margin involvement. A
      completion left lobectomy (second surgery) was performed two weeks later.
      Therefore the pathological stage is II (T3N0M0). She received adjuvant
      radioactive iodine ablation for residual thyroid tissue. By 2003, she developed
      local recurrence, which was resected (third surgery), followed by adjuvant
      external beam radiotherapy. Unfortunately, she developed further recurrence in
      the left main bronchus, as identified by Indium-111 Octreotide (Curium, Missouri,
      USA) and positron emission tomography-computed tomography PET-CT imaging in 2006.
      She underwent a left pneumonectomy (fourth surgery) in July 2006. In November
      2007 she was found to have mediastinal recurrence which was treated with high
      dose external beam radiotherapy. She initially responded but developed more local
      recurrence and a lung metastasis by 2011. She was treated with brivanib with
      ixabepilone, under a phase I clinical trial with mixed response. Her treatment
      was discontinued secondary to toxicity and she succumbed to her disease in 2012.
      This case report illustrates the natural history and clinical decision making for
      patients diagnosed with HCC of the thyroid. Specifically, we highlight the
      clinical issues surrounding the histopathological diagnosis, extent of surgical
      resection, radioiodine diagnostic imaging/ablative treatment, as well as external
      beam radiotherapy.

PMID- 28507840
TI  - Cadaver-based Necrotizing Fasciitis Model for Medical Training.
AB  - Necrotizing fasciitis is a devastating infectious disease process that is
      characterized by extensive soft tissue necrosis along deep fascial planes,
      systemic toxicity, and high mortality. Ultrasound imaging is a rapid and non
      invasive tool that can be used to help make the diagnosis of necrotizing
      fasciitis by identifying several distinctive sonographic findings. The purpose of
      this study is to describe the construction of a realistic diagnostic training
      model for necrotizing fasciitis using fresh frozen cadavers and common,
      affordable materials. Presently, fresh non-embalmed cadavers have been used at
      medical institutions for various educational sessions including cadaver-based
      ultrasound training sessions. Details for the preparation and construction of a
      necrotizing fasciitis cadaver model are presented here. This paper shows that the
      images obtained from the cadaver model closely imitate the ultrasound appearance
      of fluid and gas seen in actual clinical cases of necrotizing fasciitis.
      Therefore, it can be concluded that this cadaver-based model produces high
      quality sonographic images that simulate those found in true cases of necrotizing
      fasciitis and is ideal for demonstrating the sonographic findings of necrotizing
      fasciitis.

PMID- 28507841
TI  - Skin Necrosis Caused by Simple Massage Equipment.

PMID- 28507842
TI  - Pyoderma Gangrenosum after Deep Inferior Epigastric Perforator Breast
      Reconstruction: Systematic Review and Case Report.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is a rare skin disorder of the neutrophilic
      dermatoses spectrum that can mimic wound infections in surgical patients. PG
      after breast surgery has been reported but in limited amounts in autologous
      breast reconstruction patients. We present the first case of PG after a delayed
      bilateral deep inferior epigastric perforator flap breast reconstruction in the
      setting of systemic disease along with a systematic review. METHODS: PubMed,
      Ovid, and Web of Science were systematically searched to obtain cases of PG after
      autologous breast reconstruction. Sixty articles were identified but only 16 were
      relevant to this study. RESULTS: Systemic disease was present in 2 patients
      (13%). Wound onset occurred typically 5 days after surgery. Fever and/or
      leukocytosis was observed in 10 patients (63%). Wound cultures were positive in 2
      patients (13%). Donor-site wounds were present in 9 patients (56%). Bilateral
      breast wounds were present in 67% of bilateral cases. Debridement was performed
      in 10 cases (63%). Skin graft or substitute was performed in 6 cases (38%).
      Resection of autologous flap was performed in 3 cases (19%). All patients were
      treated with systemic steroids (81%) and/or immunosuppressive medications (50%).
      Complete wound healing occurred by 4 months on average. CONCLUSION: If early
      ulcerative wounds develop at multiple sites after autologous breast
      reconstruction with worsening after debridement and antibiotic therapy, then PG
      should be considered. It is imperative that an early diagnosis and subsequent
      treatment with steroids and/or immunosuppressive medications be initiated so
      further surgical procedures, flap loss, and scarring can be minimized.

PMID- 28507843
TI  - A New Local Flap Nipple Reconstruction Technique Using Dermal Bridge and
      Preoperatively Designed Tattoo.
AB  - BACKGROUND: Nipple-areolar reconstruction is the final step in breast
      reconstruction. Reconstruction using local flaps and tattooing is useful in cases
      of bilateral reconstruction, a small nipple-areolar complex (NAC) as the donor
      site, and avoiding disturbance of the normal side and other body parts. However,
      this method can cause projection loss and color fading of the nipple. Moreover,
      the breast mound is reconstructed with an implant. METHODS: We performed nipple
      areolar reconstruction of 90 nipples using clover-designed flaps oriented at 120
      degrees and tattooing after breast silicone implantation in 64 women. The tattoo
      was designed before flap operation and stained darker. Following donor site
      closure, a dermal flap was made as a bridge for nipple support. The nipple space
      was separated by the dermal flap from the breast mound and was filled with
      subcutaneous tissue. The size of the reconstructed nipple projection was measured
      postoperatively and 1 year later. The projection maintenance rate was calculated.
      RESULTS: The heights of the nipple projection were 11.3 +/- 1.8 mm (95%
      confidence interval [CI]: 10.9-11.7) just after the operation and 6.09 +/- 2.4 mm
      (95% CI: 5.6-6.6) 1 year later. The actual range of nipple projection between
      these 2 heights was 5.2 +/- 2.4 mm (95% CI: 4.7-5.7). The maintenance rate of the
      reconstructed nipple projection after 12 months was 54.1 +/- 20.9 (95% CI: 49.7
      58.5). The nipple color was maintained for over a year. CONCLUSIONS: Our nipple
      areolar reconstruction technique could maintain the projection and color of the
      reconstructed nipple for a long period. Good outcomes were obtained in this
      implant-based breast reconstruction.

PMID- 28507845
TI  - Surgical Factors Associated with Prolonged Hospitalization after Reconstruction
      for Oncological Spine Surgery.
AB  - BACKGROUND: Posterior trunk reconstruction is increasingly possible as a result
      of advances in spinal instrumentation, reconstructive approaches, and
      perioperative critical care. Extensive cases often require a muscle flap or
      complex closure to obliterate dead space. Postsurgical wound complications and
      subsequent reoperations can lead to neural injury, higher hospital costs, and
      longer hospitalizations. We aim to identify risk factors that are associated with
      increased length of stay (LOS) for patients receiving flaps to close a spinal
      defect. METHODS: A single institution, retrospective cohort study was performed
      on all patients from 2002 to 2014 who received a muscle flap to close a spine
      defect. Medical and perioperative variables that were significantly associated
      with LOS (P < 0.05) in univariate analysis were included in a stepwise regression
      model. RESULTS: A total of 288 cases were identified. Presence of
      instrumentation, preoperative chemotherapy, wound dehiscence, cerebrospinal fluid
      leak, partial/total flap loss, and medical morbidity occurrence were all
      independently associated with increased LOS in a combined multivariate model (P <
      0.02 for each of the 6 variables). Importantly, Kaplan-Meier analysis
      demonstrated that postoperative wound dehiscence increased LOS by 12 days.
      CONCLUSIONS: Spinal tumor resections often create large cavitary defects that
      necessitate the use of muscle flaps for closure. Patients who have received
      adjuvant chemotherapy require instrumentation, or those who develop specific
      wound-related or medical complications are at increased risk for prolonged
      hospitalization after spinal reconstruction. Thus, implementing measures to
      mitigate the occurrence of these adverse events will reduce costs and decrease
      the length of hospitalization.

PMID- 28507844
TI  - An Innovative Risk-Reducing Approach to Postmastectomy Radiation Delivery after
      Autologous Breast Reconstruction.
AB  - INTRODUCTION: Postmastectomy radiation therapy (PMRT) has known deleterious side
      effects in immediate autologous breast reconstruction. However, plastic surgeons
      are rarely involved in PMRT planning. Our institution has adopted a custom bolus
      approach for all patients receiving PMRT. This offers uniform distribution of
      standard radiation doses, thereby minimizing radiation-induced changes while
      maintaining oncologic safety. We present our 8-year experience with the custom
      bolus approach for PMRT delivery in immediate autologous breast reconstruction.
      METHODS: All immediate autologous breast reconstruction patients requiring PMRT
      after 2006 were treated with the custom bolus approach. Retrospective chart
      review was performed to compare the postirradiation complications, reconstruction
      outcomes, and oncologic outcomes of these patients with those of previous
      patients at our institution who underwent standard bolus, and to historical
      controls from peer-reviewed literature. RESULTS: Over the past 10 years, of the
      29 patients who received PMRT, 10 were treated with custom bolus. Custom bolus
      resulted in fewer radiation-induced skin changes and less skin tethering/fibrosis
      than standard bolus (0% vs 10% and 20% vs 35%, respectively), and less volume
      loss and contour deformities compared with historical controls (10% vs 22.8% and
      10% vs 30.7%, respectively). CONCLUSIONS: Custom bolus PMRT minimizes radiation
      delivery to the internal mammary vessels, anastomoses, and skin; uniformly doses
      the surgical incision; and provides the necessary radiation dose to prevent
      recurrence. Because custom bolus PMRT may reduce the deleterious effects of
      radiation on reconstructive outcomes while maintaining safe oncologic results, we
      encourage all plastic surgeons to collaborate with radiation oncologists to
      consider this technique.

PMID- 28507846
TI  - Contracted Nose Correction with Dermofat and Conchal Cartilage.

PMID- 28507847
TI  - Plastic and Reconstructive Surgery in Global Health: Let's Reconstruct Global
      Surgery.
AB  - Since the inception of the Lancet Commission in 2013 and consequent
      prioritization of Global Surgery at the World Health Assembly, international
      surgical outreach efforts have increased and become more synergistic. Plastic
      surgeons have been involved in international outreach for decades, and there is
      now a demand to collaborate and address local need in an innovative way. The aim
      of this article was to summarize new developments in plastic and reconstructive
      surgery in global health, to unify our approach to international outreach.
      Specifically, 5 topics are explored: current models in international outreach,
      benefits and concerns, the value of research, the value of international surgical
      outreach education, and the value of technology. A "Let's Reconstruct Global
      Surgery" network has been formed using Facebook as a platform to unite plastic
      and reconstructive surgeons worldwide who are interested in international
      outreach. The article concludes with actionable recommendations from each topic.

PMID- 28507848
TI  - The Marriage of Sartorius and Tensor Fasciae Latae in Treating Vascular
      Prosthetic Graft Infections.
AB  - BACKGROUND: Vascular prosthetic graft infection in the groin is associated with
      high morbidity and mortality. This article presents a case series on the use of 2
      flaps in the treatment of this condition. METHODS: Five patients, mean age 65
      years (range, 49-74 years), with significant comorbidity were treated for an
      exposed and infected vascular prosthetic graft in the groin with a combination of
      sartorius muscle (SM) flap and tensor fascia lata (TFL) myocutaneous flap after
      debridement and start of microbiologic culture-guided antibiotic treatment. The
      SM flap was used to cover the exposed graft. To obtain stable wound coverage, the
      SM and remaining groin defect were closed with a pedicle TFL flap. RESULTS: All
      flaps survived, with only 1 TFL flap suffering a small tip necrosis. All patients
      obtained stable wound coverage. Donor-site morbidity was minimal. During the
      follow-up, mean 46 months (range, 15-79 months), 1 patient had a recurrence after
      15 months due to a kink in the elongated prosthetic graft that protruded through
      the skin alongside the SM and TFL flaps. CONCLUSIONS: The combination of SM and
      TFL flaps could be a new treatment option for patients who have an exposed and
      infected vascular prosthetic graft in the groin. This flap combination could also
      be used as a prophylactic procedure for those patients with a high risk to
      develop such a serious complication.

PMID- 28507849
TI  - Difference in Success Treating Proximal Interphalangeal and Metacarpophalangeal
      Joints with Collagenase: Results of 208 Treatments.
AB  - BACKGROUND: Dupuytren disease (DD) is a fibroproliferative disorder of the palmar
      fasciae causing extension deficit and impaired hand function. Treatment with
      injection of collagenase clostridium histolyticum (CCH) is a nonsurgical
      treatment method. The aim of this study was to evaluate the difference in
      efficiency and recurrence at 12-month follow-up when treating metacarpophalangeal
      (MP) and proximal interphalangeal (PIP) joints with CCH. None of the patients had
      received previous treatments of their condition. METHODS: This study is a
      prospective study of a consecutive series of patients with DD presenting with an
      extension deficit greater than 20 degrees  affecting the MP or PIP joint.
      RESULTS: We found a mean reduction in extension deficit of 47 degrees  (91%) for
      MP joints and 47 degrees  (76%) for PIP joints. Full correction (max 5 degrees 
      deficit) was achieved in 76% of MP and 28% of PIP joints. Skin rupture was seen
      in 34% of treatments. The 1-year relapse rate was 15% for MP and 67% for PIP
      joints. The reduction in quickDASH score was only statistically significant for
      MP joints at 1 year. Eighty-one percent of all patients reported being satisfied
      or very satisfied. No major adverse events were recorded. CONCLUSION: Excellent
      results can be achieved in the treatment of MP-joint contractures, whereas the
      success rate is significantly lower and recurrence rate is greater for PIP
      joints.

PMID- 28507850
TI  - Distally Based Sural Artery Peroneus Flap (DBSPF) for Foot and Ankle
      Reconstruction.
AB  - BACKGROUND: Reconstruction of soft-tissue defects in lower third of leg, ankle,
      and foot has been a challenge and reconstructive surgeons have been trying to
      innovate different flaps. To solve this issue, we propose a distally based sural
      artery peroneus flap (DBSPF) in which we include superficial portion of the
      peroneus brevis muscle and its blood supply with the peroneal artery distally.
      The aim of this study was to evaluate the functional outcome and its usefulness
      over conventional distal sural artery flap or other local options available.
      METHODS: This is a case series of 20 patients that include a DBSPF that was done
      for defects around ankle, distal leg, and foot caused by trauma or tumor ablation
      within the period of June 2013 to March 2015 in Kasralainy Hospital, Cairo. All
      cases were evaluated according to flap vascularity, distal reach of flap,
      aesthetic outcome, and donor-site morbidity. RESULTS: All flaps survived. One
      flap developed venous congestion that subsided spontaneously with limb elevation.
      The flap dimension ranged from 42 cm to 442 cm2, and it reached the midfoot
      easily. The pivot point was kept as low as 2-6 cm from lateral malleolus
      according to location of perforators. The ankle stability was maintained, and the
      desired aesthetic outcome was achieved. CONCLUSIONS: The DBSPF is an addition to
      the armamentarium in plastic surgery for defects around ankle, distal leg, and
      foot. It is an easy and swift procedure as compared with complex microsurgical
      reconstruction.

PMID- 28507851
TI  - Reconstruction after Excision of Hidradenitis Suppurativa: Are Skin Grafts Better
      than Flaps?

PMID- 28507852
TI  - Survival Differences in Women with and without Autologous Breast Reconstruction
      after Mastectomy for Breast Cancer.
AB  - BACKGROUND: Breast reconstruction (BR) is an option for women who are treated
      with mastectomy; however, there has been concern regarding the oncologic safety
      of BR. In this study, we evaluated recurrences and mortality in women treated
      with mastectomy and compared outcomes in those treated with mastectomy alone to
      those with mastectomy plus transverse rectus adbominis (TRAM) flap BR. METHODS:
      The prospective cohort study included women treated with mastectomy at Women's
      College Hospital from 1987 to 1997. Women with TRAM flap BR were matched to
      controls based on age and year of diagnosis, stage, and nodal status. Patients
      were followed from the date of diagnosis until death or date of last follow-up.
      Hazard ratios were generated to compare cases and controls for outcome variables
      using Cox's proportional hazards models. RESULTS: Of 443 women with invasive
      breast cancer, 85 subjects had TRAM flap BR. Sixty-five of these women were
      matched to 115 controls. The mean follow-up was 11.2 (0.4-26.3) years. There were
      no significant differences between those with and without BR with weight, height,
      or smoking status. Women with TRAM flap were less likely to experience a distant
      recurrence compared to women without a TRAM flap (relative risk, 0.42; P =
      0.0009) and were more likely to be alive (relative risk, 0.54; P = 0.03).
      CONCLUSIONS: Women who elect for TRAM flap BR after an invasive breast cancer
      diagnosis do have lower rates of recurrences and mortality than women treated
      with mastectomy alone. This cannot be explained by differences in various
      clinical or lifestyle factors.

PMID- 28507854
TI  - A Novel Needle Structure that Can Avoid Intravascular Injection of Any Filler.
AB  - With increasing use of dermal fillers, more and more adverse effects are
      reported. The most devastating one is intravascular injection. We propose a novel
      needle prototype that allows physicians to prevent intravascular injection.

PMID- 28507853
TI  - Ulnar Head Reconstruction with Microvascular Second Metatarsal.
AB  - BACKGROUND: The distal radioulnar joint along with the interosseous ligament of
      the forearm and the proximal radioulnar joint, form a functionally integrated
      system responsible for the pronation-supination of the hand. The distal ulna, the
      so-called ulnar head, is an integral part of this system. Apart from its well
      known role in forearm rotation, the ulnar head is essential in transverse load
      transmission through the distal radioulnar joint upon resisted elbow flexion.
      Autologous reconstruction of ulnar head would theoretically be beneficial with
      respect to prostheses. METHODS: Three cases of ulnar head reconstruction with
      microvascular second metatarsal are reported herein including trauma,
      oncological, and congenital ethiologies. RESULTS: The clinical result was good
      without complaints of instability. CONCLUSIONS: The cases included in this
      series, although heterogeneous, indicate that this treatment may be feasible also
      in postoncological resections and in congenital cases.

PMID- 28507855
TI  - Composite Arteriovenous Radial Conduit Flap for Lower Limb Reconstruction.
AB  - In complex lower limb trauma, the healthy recipient vessels can be far from the
      defect to be reconstructed due to the usually high-energy injury sustained. The
      use of vein grafts, either directly or in the form of arteriovenous loops, is the
      usual solution in these cases. In the vein graft donor-depleted patient, other
      options are required; the composite arteriovenous radial conduit flap may be a
      useful resort in these situations.

PMID- 28507856
TI  - Reverse Radial Forearm Flap.
AB  - Supplemental Digital Content is available in the text.

PMID- 28507858
TI  - Reconstructing Discontinuous Facial Defects with Simultaneous Ulnar Perforator
      Free Flaps.
AB  - Multiple, simultaneous skin cancers of the face are common. This is the first
      description of reconstructing discontinuous facial defects (i.e., separate sites
      of the face) with simultaneous ulnar perforator flaps. The distinct innovations
      of this multiple flap design are the ability to restrict the harvest site to one
      extremity, to obtain vein and arterial grafts from the same extremity, and to
      create multiple flaps with minimal hirsutism and bulk. We present a case of a 57
      year-old male with multiple basal cell carcinomas who underwent wide local
      excisions of the right upper lip and cheek and of the left lower eyelid and
      infraorbital cheek. Two left-sided ulnar perforator free flaps were used for
      reconstruction with the outcome of normal oral competence and eyelid function.
      When faced with discontinuous facial defects, reconstruction with simultaneous
      ulnar perforator flaps is a useful option because of the advantages of matching
      the thinness and pliability of the resected skin, reducing the number of harvest
      sites and preventing the distortion and contraction that can be seen with local
      advancement flaps or skin grafts.

PMID- 28507857
TI  - Greater Omental Lymph Node Flap for Upper Limb Lymphedema with Lymph Nodes
      depleted Patient.
AB  - BACKGROUND: The greater omentum is supplied by the right, middle, and left
      omental arteries, which arise from the right and left gastroepiploic arteries.
      All or part of the greater omentum can be harvested based on this blood supply
      for free tissue transfer. It has stimulated new interest in its use as the donor
      site in the treatment of lymphedema. For patients who have failed other
      management options or have limited peripheral lymph node donor sites, the greater
      omental lymph node flap may offer the best chance for lymphedema treatment.
      METHODS: We report a 59-year-old woman with a history of left breast cancer who
      was treated with left modified radical mastectomy and axillary lymph node
      dissection and developed left upper extremity Grade IV lymphedema. She received
      vascularized groin lymph node transfer and lymphaticovenous anastomosis, but the
      result was not satisfactory. She also had nasopharyngeal cancer that was treated
      with radiotherapy to the head and neck, making use of the submental lymph nodes
      flap impossible. Due to a lack of other options of lymph node donor sites, the
      split greater omental lymph node flap (GOLF) was used. RESULTS: After surgery, it
      showed an arm circumference reduction of 42.9% above the elbow and 36.4% below
      the elbow at an 8-month follow-up. There was no intraabdominal complication.
      CONCLUSIONS: The split GOLF has shown good results in a peripheral lymph node
      depleted lymphedema patient. Using a laparoscopic technique for flap harvest has
      less risk of donor site morbidity and hides scarring.

PMID- 28507859
TI  - The Double Volar Flap Technique for Aesthetic Repair of Syndactyly and
      Polysyndactyly of Toe without Skin Grafting.
AB  - BACKGROUND: Aesthetic repair of syndactyly of the toes is desirable because
      patients may have psychological concerns about its appearance. There are 2
      important factors for the aesthetic repair of syndactyly of the toe. One is to
      hide the operative scar from the visual site (dorsal site), whereas the other is
      to create an interdigital space close to the normal anatomical skin
      characteristics (2 general types of skin: glabrous and hairy). METHODS: In total,
      12 patients (4 males and 8 females) with 15 syndactylous webs were operated on by
      using the double volar flap technique. The following 3 local flaps were designed
      with this technique: an M-shaped flap designed on the dorsal side of the
      interdigital region (flap A) and double volar flaps (flaps B and C) designed on
      the volar side of the interdigital region. Flap A was used for reconstruction of
      the web slope, whereas flaps B and C were used for reconstruction of the proximal
      sidewall of toes. RESULTS: The corrected toes showed a deep and natural
      interdigital commissure with no exposure of skin grafts or conspicuous scars on
      the dorsal visible side. The scars on the volar side were also inconspicuous.
      CONCLUSIONS: The double volar flap method for repair of syndactyly and
      polysyndactyly of the toes has the same advantages as those of the local flap
      method, in addition to an optimum aesthetic result through matching with the
      normal anatomical skin characteristic of the interdigital space and hiding of the
      operative scar from the visual site.

PMID- 28507860
TI  - Aging and Sexual Differences of the Human Skull.
AB  - BACKGROUND: The aging process of the face comprises all layers: skin,
      subcutaneous fat, muscles, and skeleton, and the signs of aging depend mainly on
      which layer is mostly affected. OBJECTIVE: To evaluate the aging facial skeleton,
      as well as establish the sexual differences, areas with a strong predisposition
      to resorption, and aesthetic repercussion for better treatment approach. METHODS:
      Skulls from the Forensic Anthropology Department of the Institute of Forensic
      Medicine of Belo Horizonte, Brazil, were classified according to gender and age
      group (i.e., <20 years, 20-50 years, >50 years). Structural changes were
      classified according to gender and age group. RESULTS: Of the 241 skulls
      included, 192 were male skulls and 49 female. Sexual dimorphism and age-related
      peculiarities are described herein. CONCLUSIONS: The knowledge of the anatomy of
      the aging face, taking into consideration all the layers (skin, fat pads,
      muscles, and bones), as a whole, for the treatment of folds and shadows is vital
      for a better and more natural final aesthetic outcome.

PMID- 28507861
TI  - Absence of Ulnar Artery Inflow Detected by Allen's Test Prior to Radial Forearm
      Free Flap.
AB  - Radial forearm free flaps are commonly used for soft-tissue reconstruction after
      resection of head and neck cancer. It is perfused by the radial artery, leaving
      the ulnar artery for perfusion of the hand and digits. The absence of distal
      ulnar artery and associated superficial palmar arch, however, has not been
      reported in cadaveric dissection. We report a case of unilateral ulnar artery
      flow absence, detected by Allen's test, during preoperative preparation for a
      radial forearm free flap. Based on the simplicity, safety, and ease, we recommend
      Allen's test to be performed preoperatively on every patient for whom such a flap
      is a consideration.

PMID- 28507862
TI  - Eyelid Reconstruction Using Oral Mucosa and Ear Cartilage Strips as Sandwich
      Grafting.
AB  - BACKGROUND: The eyelid structure can be divided into an inner layer and an outer
      layer. Reconstruction of a full-thickness eyelid defect is accomplished by full
      thickness composite tissue transfer or combined layered reconstruction. We
      present a new technique for inner layer reconstruction using ear cartilage and
      oral mucosa. METHODS: The oral mucosa graft is harvested from the inner side of
      the lower lip to fit the defect size and shape. The ear cartilage graft is
      harvested as a rectangular strip. The harvested mucosa is sutured to the defect
      margin and the cartilage strip graft is interposed to the defect. Finally, the
      outer layer of the defect is covered with skin flaps. Consequently, the ear
      cartilage graft is sandwiched between the mucosa graft and the skin flap.
      RESULTS: We used this technique for the reconstruction of 13 full-thickness
      eyelid defects of various locations, sizes, and shapes. Ten cases involved the
      lower eyelid, 2 cases involved the lower eyelid including the medial canthus, and
      1 case involved the upper eyelid. The oral mucosa graft survived in all patients.
      The reconstructions were successful and there were no postoperative reports of
      conjunctival or corneal irritation. CONCLUSIONS: The present technique using a
      combination of an ear cartilage strip graft and oral mucosa graft is an easy and
      versatile technique for reconstruction of inner layer eyelid defects. We believe
      that the beneficial effects of tears, which are richly oxygenated, improved
      survival of the grafted mucosa.

PMID- 28507864
TI  - Technical Tip: Mark Scarpa's Fascia to Facilitate Proper Abdominal Closure During
      Autologous Breast Reconstruction.

PMID- 28507863
TI  - Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis.
AB  - BACKGROUND: Amniotic membrane is tissue obtained from human placenta rich in
      cytokines, growth factors, and stem cells that possess the ability to inhibit
      infection, improve healing, and stimulate regeneration. METHODS: A meta-analysis
      was performed examining randomized controlled trials comparing amniotic tissue
      products with standard of care in nonhealing diabetic foot ulcers including
      PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database
      of Systematic Reviews. RESULTS: A search of 3 databases identified 596
      potentially relevant articles. Application of selection criteria led to the
      selection of 5 randomized controlled trials. The 5 selected randomized controlled
      trials represented a total of 311 patients. The pooled relative risk of healing
      with amniotic products compared with control was 2.7496 (2.05725-3.66524, P <
      0.001). CONCLUSIONS: The current meta-analysis indicates that the treatment of
      diabetic foot ulcers with amniotic membrane improves healing rates in diabetic
      foot ulcers. Further studies are needed to determine whether these products also
      decrease the incidence of subsequent complications, such as amputation or death,
      in diabetic patients.

PMID- 28507865
TI  - Reconstitution of Human Keloids in Mouse Skin.
AB  - BACKGROUND: Keloids are a dermal fibroproliferative scar of unknown etiology.
      There is no good animal model for the study of keloids, which hinders the
      development and assessment of treatments for keloids. METHODS: Human
      keratinocytes and dermal fibroblasts were isolated from 3 human skin tissues:
      normal skin, white scars, and keloids. A mixed-cell slurry containing
      keratinocytes and dermal fibroblasts was poured into a double chamber implanted
      on the back of NOD/Shi-scid/IL-2Rgammanull mice. After 12 weeks, the recipient
      mice had developed reconstituted human skin tissues on their backs. These were
      harvested for histological studies. RESULTS: Macroscopically, the reconstituted
      skins derived from both normal skin and white scars were similar to normal skin
      and white scars in humans, respectively. Keloid-derived reconstituted skins
      exhibited keloid-like hypertrophic nodules. Histological findings and
      immunohistochemical staining confirmed that the reconstituted skin tissues were
      of human origin and the keloid-derived reconstituted skin had the typical
      features of human keloids such as a hypertrophic dermal nodule, collagen type
      composition, orientation of collagen fibers, and versican expression. CONCLUSION:
      The mouse model with humanized keloid tissue presented here should be a useful
      tool for future keloid research.

PMID- 28507867
TI  - Low-grade Cribriform Cystadenocarcinoma: A Review of the Literature and Case
      Report.
AB  - Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor of the salivary
      gland that most often arises from the parotid gland. A 51-year-old man developed
      a small mass on the right parotid gland 5 years ago. A preoperative magnetic
      resonance image showed abnormal intensity, an atypical characteristic for such a
      tumor; therefore, the diagnosis was difficult. Thus, a superficial parotidectomy
      was performed as a total excisional biopsy to remove the tumor. Histopathological
      analyses revealed that the tumor was composed of a single cyst comprising cells
      containing mucosal fluid, with proliferation of large cells. Also, proliferation
      of the tumor epithelium showed a papillary cribriform pattern of proliferation
      with a partial ring form, and the tissue inside the tumor was replaced by a
      hematoma. Mild cellular atypia was observed. Immunostaining for S-100 was
      positive, and the Ki-67 ratio was <5%. These histopathological findings led to a
      diagnosis of LGCCC of the parotid gland. At 54 months after surgery, the patient
      has had no recurrence or facial palsy. LGCCC is a rare neoplasm of the salivary
      gland and is listed in the current World Health Organization classification
      (2005) as a variant of cystadenocarcinoma. This case suggests that a thorough
      preoperative examination can lead to better diagnosis of rare tumors, including
      LGCCC. Thus, if a plastic surgeon is to correctly diagnose and treat parotid
      grand tumors, including LGCCC, then a detailed preoperative examination,
      including imaging, a disease course review, a physical examination, and
      differential diagnosis, should be considered carefully.

PMID- 28507868
TI  - Chronological Order of Lipofilling during Implant Exchange.

PMID- 28507866
TI  - Establishing Content Validity of the CLEFT-Q: A New Patient-reported Outcome
      Instrument for Cleft Lip/Palate.
AB  - BACKGROUND: The CLEFT-Q is a new patient-reported outcome instrument designed to
      measure outcomes that matter to patients. The aim of this qualitative study was
      to establish content validity of the CLEFT-Q in patients who differ by age and
      culture. METHODS: Patients aged between 6 and 29 years were recruited from
      plastic surgery clinics in Canada, India, Ireland, the Philippines, the
      Netherlands and the United States. Healthcare providers and other experts
      participated in a focus group or provided individual feedback. Input was sought
      on all aspects of the CLEFT-Q (item wording, instructions, and response options),
      and to identify missing content. Patient interviews and expert feedback took
      place between September 2013 and September 2014. RESULTS: Sixty-nine patients and
      44 experts participated. The first draft of the CLEFT-Q consisted of 163 items
      measuring 12 constructs. The first round of feedback identified 92 items that
      required revision. In total, 3 rounds of interviews, and the involvement of an
      artist to create pictures for 17 items, were needed to establish content
      validity. At the conclusion of cognitive interviews, the CLEFT-Q consisted of 13
      scales (total 171 items) that measure appearance, health-related quality of life,
      and facial function. The mean Flesch-Kincaid readability statistic for items was
      1.4 (0 to 5.2). CONCLUSION: Cognitive interviews and expert review allowed us to
      identify items that required re-wording, re-conceptualizing, or to be removed, as
      well as any missing items. This process was useful for refining the CLEFT-Q
      scales for further testing.

PMID- 28507869
TI  - Superficial Circumflex Iliac Artery Perforator Flap for Dorsalis Pedis
      Reconstruction.
AB  - Reconstruction of dorsalis pedis with soft tissue is challenging because it needs
      to preserve thin structure to ensure that the patient will be able to wear shoes.
      Here, we report the use of a thin superficial circumflex iliac artery perforator
      (SCIP) flap in dorsalis pedis reconstruction. A 67-year-old man presented with a
      third-degree burn, which exposed his extensor tendons. A thin SCIP flap from the
      left inguinal region measuring 15 * 4 cm was transferred to the dorsalis pedis
      region. Postoperatively, no major cosmetic or functional problems were observed.
      Because the invasiveness of the donor site is nearly same between SCIP flap and
      skin graft from inguinal region, SCIP flap is better solution in point of
      textural qualities for dorsalis pedis reconstruction.

PMID- 28507870
TI  - Intraoperative Change in Defect Size during Maxillary Reconstruction Using
      Surgical Guides Created by CAD/CAM.
AB  - Surgical osteotomy guides created by computer-aided design/computer-aided
      manufacturing (CAD/CAM) have been developed and are now widely used in
      maxillofacial reconstruction. However, there are no standard procedures for
      dealing with an intraoperative change in defect size. We report on a case in
      which we used our CAD/CAM guides to deal with an intraoperative change in defect
      size in a maxillary reconstruction. We planned the maxillary reconstruction using
      a free fibula flap because of left maxillary sinus cancer in a 73-year-old man.
      In Japan, we cannot use commercially supplied CAD/CAM guides because these have
      not been approved by the government. We created novel CAD/CAM guides by using
      free software and a low-cost 3D printer. We performed model surgery to check the
      accuracy of the design and to prebend the titanium plates before the operation.
      The actual defect in the maxilla was found to be smaller than that used in
      preoperative planning. It was therefore necessary to rearrange the fibular
      segments and to rebend the plates. Comparison between the preoperative and
      postoperative 3D images showed that the deviation was 2-4 mm. In case that the
      CAD/CAM guides become inapplicable because of an intraoperative change in defect
      size, rearranging both the ends of set-up fibular segments and rebending the
      plates in situ allows us to deal with the situation. However, because extra time
      is needed to rearrange and rebend, the total operation and flap ischemic times
      are not shortened.

PMID- 28507871
TI  - Mammary Malignant Ulcer after Radiotherapy: Unpleasant Surprise.
AB  - We present a case of a woman, 79 years old, followed by Psychiatry for depressive
      episodes after breast cancer removal. She was operated on for ductal breast
      carcinoma in 1983. Afterward she was submitted to adjuvant radiotherapy. She came
      to our attention for a chronic skin ulcer that developed into the radio-treated
      area about 4 years ago. We performed a skin biopsy and programed adipose tissue
      grafts to promote wound healing. The result of the biopsy was unexpected: dermal
      localization of not differentiated breast carcinoma. She is currently under
      systemic chemotherapy treatment. The key message is to always perform a skin
      biopsy of a chronic skin ulcer developed after breast cancer removal before
      planning surgical reconstruction.

PMID- 28507872
TI  - Multiple-level Replantation in Elderly Patients: Risk Versus Benefit.
AB  - Multiple-level amputations of the upper extremity represent a surgical challenge
      generally only attempted in young patients. This case demonstrates a successful
      replantation in an elderly woman. The postoperative course was complicated by
      disseminated intravascular coagulopathy most likely due to inadequate
      resuscitation. Hand trauma is often underestimated in its general severity. Upper
      extremity amputations need to be handled similar to polytraumatized patients.

PMID- 28507873
TI  - Inferior Limb Salvage by Combined Free-tissue Transfer and the Crane Principle
      Revisited.
AB  - Aggressive treatment of ischemia of the lower extremities has decreased the
      number of amputations in both diabetic and nondiabetic patients; combined
      vascular reconstruction and microvascular free-flap transfer has been used to
      improve distal perfusion and cover large tissue defects caused by the critical
      limb ischemia during the past 30 years. We present our experience with a 71-year
      old diabetic patient who underwent revascularization with a vascular bypass and a
      simultaneous microvascular flap reconstruction for limb salvage after domestic
      trauma. An extension of the "crane" principle was used to solve bypass exposure
      due to wound late complication. After 1-year follow-up, the patient was able to
      walk without pain. Combining 3 well-established methods of arterial
      revascularization and free-flap transfer and the old "crane principle," we
      achieved limb salvage, offering an alternative to below-knee amputation.

PMID- 28507874
TI  - A 10-year Follow-up of a Free Vascularized Fibula Flap Clavicle Reconstruction in
      an Adult.
AB  - The free vascularized fibula flap has been widely used for clavicle
      reconstruction. Limited evidence exists for the long-term outcome of clavicle
      reconstruction using the free vascularized fibula flap in adults. We report the
      functional and aesthetic outcome in a 52-year old man a decade after clavicle
      reconstruction using a free vascularized fibula flap in combination with a
      modified Richardson Hook Plate. At the 10-year follow-up, panoramic shoulder X
      ray showed the modified Richardson Hook Plate had remained firmly in place with
      the fibula and the hook positioned beneath the acromion. Functionally, the
      patient presented with a constant shoulder score of 77, with a pain-free
      symmetrical full range of motion. In conclusion, reconstruction of lateral
      clavicle defect using free vascularized fibula flap in conjunction with modified
      Richardson Hook plate may provide patients with excellent long-term functional
      and aesthetic outcomes.

PMID- 28507875
TI  - Digital Joint Reconstruction with Osteotendinous Joint Allograft: Experimental
      Study in Rats.
AB  - BACKGROUND: Fresh or frozen nonvascularized osteotendinous joint allografts
      (OTJA) have not been used previously, clinically or experimentally, for
      metacarpophalangeal joint reconstruction. Therefore, we evaluated the viability
      of OTJA for metatarsophalangeal joint (MTJ) reconstruction in rats. METHODS: In
      the experimental group of 12 Lewis rats, we reconstructed the MTJ of the third
      digit of the hindlimb with a fresh, nonvascularized OTJA obtained from the same
      digit from 12 donor rats. In the control group of 6 Lewis rats, an autologous
      composite osteotendinous graft of the MTJ of the same digit was obtained and
      repositioned in situ as an auto-transplant. Weight, pain, edema, dehiscence, and
      wound infection were evaluated every 24 hours for 30 days postoperatively. At the
      end of 30 days, we evaluated digit position, flexion and extension, passive
      mobility, radiological bone healing, and histological grades of rejection.
      RESULTS: We found no statistically different changes in weight, edema, pain,
      digit position, or radiological bone healing in either group. No wound dehiscence
      or infection was seen in any of the rats. Ten degrees of flexion and extension
      mobility were lost in the control group; the experimental group lost up to 30
      degrees (P = 0.009). Histologically, 9 of the experimental group rats (9/12, 75%)
      showed rejection reactions compared with none of the controls (0%) (P = 0.009).
      CONCLUSIONS: Fresh nonvascularized OTJA caused an immune reaction without
      exposure of the graft, but with bone resorption. However, the rats maintained
      digital form and alignment with decreased passive flexion and extension of 10-30
      degrees.

PMID- 28507877
TI  - Erratum: Efficacy of Autologous Platelet-rich Plasma Glue in Weight Loss Sequelae
      Surgery and Breast Reduction: A Prospective Study: Erratum.
AB  - [This corrects the article DOI: 10.1097/GOX.0000000000000823.].

PMID- 28507876
TI  - Prediction of Skin Necrosis after Mastectomy for Breast Cancer Using Indocyanine
      Green Angiography Imaging.
AB  - BACKGROUND: In immediate tissue expander reconstruction following total
      mastectomy for breast cancer, indocyanine green angiography (ICGA)-guided skin
      trimming is useful for the prevention of complications. However, instances of
      unclear ICGA contrast can occur with this method, which are difficult to judge as
      to whether preventive trimming is warranted. To further improve the mastectomy
      flap necrosis rate, more accurate objective parameters are necessary. METHODS:
      The degree of clinical improvement was compared between 81 patients trimmed
      according to the surgeon's judgment (non-ICGA group) and 100 patients with ICGA
      guided trimming (ICGA group). We then retrospectively measured 3 parameters
      [relative perfusion (RP); time (T) to reach RPmax; and slope (S = RP/T)
      reflecting the rate of increase to RPmax] by using region of interest analysis
      software and examined their relationships with skin necrosis. RESULTS: The rate
      of grade III necrosis (reaching the subcutaneous fat layer) was significantly
      lower in the ICGA group (4.8%) than in the non-ICGA group (17.8%; P < 0.05). The
      specificity of RP for the diagnosis of skin necrosis was high (98.5%; cutoff
      value, 34). However, the sensitivities of slope parameters were higher than RP.
      CONCLUSIONS: ICGA-guided trimming decreased the rate of deep skin necrosis
      requiring additional surgical treatment. Region of interest analysis indicated
      that a relatively low percentage luminescence (RP < 34) was indicative of the
      need for skin trimming, combined with a slow increase in the perfusion of the
      mastectomy skin flaps.

PMID- 28507878
TI  - Medical Journals and Social Media: More Alike Than Wanted?

PMID- 28507879
TI  - Traumatic Cervical Unilateral and Bilateral Facet Dislocations Treated With
      Anterior Cervical Discectomy and Fusion Has a Low Failure Rate.
AB  - STUDY DESIGN: Retrospective radiographic and chart review. OBJECTIVE: To define
      the rate and associated risk factors of treatment failure of anterior cervical
      fusion for treatment of cervical facet dislocations. METHODS: Between 2004 and
      2014, a retrospective review at a single level 1 trauma center identified 38
      patients with unilateral or bilateral dislocated facet(s) treated with anterior
      cervical discectomy and fusion (ACDF). Two patients were eliminated due to less
      than 30-day follow-up. Demographic data, initial neurological exams, surgical
      data, radiographic findings, and follow-up records were reviewed. RESULTS: Of the
      36 patients with facet dislocations treated with ACDF using a fixed locking
      plate, 16 were unilateral and 20 were bilateral. The mean age was 35 years (range
      13-58). Mean follow-up was 323 days (range 30-1998). There were 3 treatment
      failures (8%). Three of 7 (43%) endplate fractures failed (P < .01), and 1/28
      (4%) facet fractures failed (P = .13). The mean time to failure was 4 weeks (1-7
      weeks). One treatment failure had a facet fracture, and all 3 failures had an
      associated endplate fracture. CONCLUSION: Treatment failure occurred in 3 out of
      36 (8%) patients with facet fracture dislocations treated with anterior cervical
      discectomy, fusion, and plating. Rates of failure are lower than has been
      previously reported. Endplate fractures of the inferior level in jumped facets
      appears to be a major risk factor of biomechanical failure. However, a facet
      fracture may not be a risk factor for failure. In the absence of an endplate
      fracture, ACDF is a reasonable treatment option in patients with single-level
      cervical facet dislocation.

PMID- 28507880
TI  - Risk and Cost of Reoperation After Single-Level Posterior Cervical Foraminotomy:
      A Large Database Study.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To examine the risk of
      undergoing another cervical spine surgery after single-level posterior cervical
      foraminotomy (PCF) and analyze the costs of such reoperations. METHODS: Using the
      PearlDiver database, we created database algorithms to identify cohorts of
      patients who underwent single-level PCF and also had various reoperations of
      interest, within 1, 2, and 4 years of follow-up. We also identified the per
      patient average charge (PPAC) for each reoperation cohort. RESULTS: In the
      Medicare cohort, the incidence of any reoperation was 8.3%, 9.8%, and 10.5%
      within 1, 2, and 4 years of follow-up, respectively. The PPAC was $8520 for the
      initial PCF procedure. When a second cervical surgery was performed, the PPAC was
      $70 349 for anterior fusion, $15 760 for posterior decompression alone, and $77
      976 for posterior decompression and fusion. In the UnitedHealth cohort, the
      incidence of any reoperation was 13.6%, 16.7%, and 17.0% within 1, 2, and 4 years
      of follow-up, respectively. CONCLUSIONS: The overall incidence of another
      cervical spine operation was slightly higher in the Medicare population to that
      in previous literature, but much higher in the UnitedHealth population. The most
      common reoperation after PCF varied between the Medicare and UnitedHealth
      datasets, and costs varied widely based on the procedure performed. This study
      provides pertinent information that surgeons can use to discuss the risk of
      reoperation with their patients.

PMID- 28507881
TI  - Development and Validation of the iDI: A Short Self-Rating Disability Instrument
      for Low Back Pain Disorders.
AB  - STUDY DESIGN: Cross-sectional and longitudinal validation study. OBJECTIVE:
      Development and validation of a short, reliable, and valid questionnaire for the
      assessment of low back pain-related disability. METHODS: The iDI was created in a
      stepwise procedure: (1) its development was based on the literature and
      theoretical consideration; (2) outcome data were collected and evaluated in a
      pilot study; (3) final validations were performed based on an international
      multicenter spine surgery outcome study including 514 patients; (4) the iDI was
      programmed for a tablet computer (iPad) and tested for its clinical
      practicability. RESULTS: The final version of the iDI comprises of 8 simple
      questions related to different aspects of disability with a 5-point Likert-type
      answer scale. The iDI compared very well to the Oswestry Disability Index in
      terms of reliability and validity. The iDI was demonstrated to be suitable for
      data assessment on a tablet computer (iPad). CONCLUSIONS: The iDI is a short,
      valid, and practicable tool that facilitates routine quality assessment in terms
      of low back pain-related disability.

PMID- 28507882
TI  - Aquaporin-1 Expression in Herniated Human Lumbar Intervertebral Discs.
AB  - STUDY DESIGN: Case series. OBJECTIVE: Intervertebral disc (IVD) degeneration is
      the cause of spondylosis. The pathogenesis is poorly understood, but disc
      dehydration often plays a role. In this study, we aim to identify and quantify
      aquaporin-1 (AQP1) in ex vivo human degenerated IVDs obtained intraoperatively
      and to investigate the relationship between AQP1 levels and magnetic resonance
      imaging (MRI) T2 intensity of the disc. METHODS: Ex vivo samples of nucleus
      pulposus (NP) tissue from lumbar IVDs were obtained from 18 consecutive patients
      who underwent surgery for disc herniation at L4/5 and L5/S1 level.
      Immunohistochemistry was performed to determine the presence of AQP1 expression,
      and this was quantified by Western blot analysis. AQP1 expression was compared to
      preoperative IVD signal intensity on T2-weighted MRI. RESULTS: NP tissue was
      obtained from 18 patients (9 for L4/5 level and 9 for L5/S1 level). AQP1
      expression was detected in all samples by Western blot and immunohistochemistry.
      AQP1 expression had a linear correlation with the preoperative IVD signal
      intensity on T2-weighted MRI at L4/5 level (R2 = 0.90) and at L5/S1 level (R2 =
      0.92). AQP1 expression was 52.2 +/- 59.0 at L5/S1 level and 15.9 +/- 20.6 at L4/5
      (P = .10). CONCLUSIONS: Our results show that AQP1 can be detected in IVD
      obtained from live human subjects. Increased AQP1 expression is associated with
      greater disc hydration as measured by signal intensity on T2-weighted MRI. AQP1
      may have a role in the dehydration associated with disc degeneration.

PMID- 28507884
TI  - A Retrospective Analysis of Complications Associated With Bone Morphogenetic
      Protein 2 in Anterior Lumbar Interbody Fusion.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of our study was to
      quantify the frequency of complications associated with recombinant human bone
      morphogenetic protein 2 (rhBMP-2) use in anterior lumbar interbody fusion (ALIF).
      METHODS: The orthopedic subset of the Medicare database (PearlDiver) was queried
      for this retrospective cohort study using International Statistical
      Classification of Diseases 9 (ICD-9) and Current Procedure Terminology (CPT)
      codes for ALIF procedures with and without rhBMP-2 between 2005 and 2010.
      Frequencies of complications and reoperations were then identified within 1 year
      from the index procedure. Complications included reoperations, pulmonary embolus,
      deep vein thrombosis, myocardial infarction, nerve-related complications,
      incision and drainage procedures, wound, sepsis, pneumonia, urinary tract
      infections, respiratory, heterotopic ossification, retrograde ejaculation,
      radiculopathy, and other medical complications. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were used to assess the statistical significance.
      RESULTS: We identified a total of 41 865 patients who had an ALIF procedure. A
      total of 14 384 patients received rhBMP-2 while 27 481 did not. Overall, 6016
      (41.8%) complications within 1 year from surgery were noted within the group who
      received rhBMP-2 and 12 950 (47.1%) complications within 1 year from surgery were
      recorded in those who did not receive rhBMP-2 (OR = 0.81, CI = 0.77-0.84).
      Overall, exposure to rhBMP-2 was associated with significantly decreased odds of
      complications with exception to reoperation rates (0.9% rhBMP-2 vs 1.0% no rhBMP
      2; OR = 0.88, CI = 0.71-1.09) and radiculopathy (4.4% rhBMP-2 vs 4.3% no rhBMP-2;
      OR = 1.02, CI = 0.93-1.13). CONCLUSIONS: The use of rhBMP-2 in patients
      undergoing ALIF procedure was associated with a significantly decreased rate of
      complications. Further studies are needed to elucidate a true incidence of
      complication.

PMID- 28507883
TI  - Risk Factors for Medical and Surgical Complications Following Single-Level ALIF.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of the study
      was to determine rates of medical and surgical postoperative complications
      following anterior lumbar interbody fusion (ALIF) along with their associated
      predictors. METHODS: Using the American College of Surgeons National Surgical
      Quality Improvement database, patients who underwent single-level ALIF surgery
      from 2006 to 2013 were identified. The 30-day rate of postoperative medical and
      surgical complications along with associated risk factors were evaluated by
      multivariable logistic regression. RESULTS: In total, 1474 patients were included
      in the analysis. The overall rate of complications was 14.5%. The medical
      complication rate was 12.7%, while the surgical complication rate was 2.8%.
      Predictors of surgical complications were diabetes (odds ratio [OR] = 2.79, 95%
      CI = 1.20-6.01, P = .009), corticosteroid dependence (OR = 4.94, 95% CI = 1.73
      14.08, P = .003), and preoperative transfusion of >4 units (OR = 7.12, 95% CI =
      1.43-35.37, P = .016). Predictors of medical complications were longer operative
      times (OR = 4.25, 95% CI = 2.90-6.24, P < .001), preoperative anemia (OR = 2.29,
      95% CI = 1.50-3.50, P < .001), >10% weight loss prior to surgery (OR = 6.79, 95%
      CI = 1.01-45.93, P = .049), and more severe American Society of Anesthesiologists
      classification (OR = 2.18, 95% CI = 1.54-3.11, P < .001). CONCLUSIONS: The
      present study determines postoperative medical and surgical complications among
      patients undergoing ALIF. The risk factors elucidated in this study indicate that
      clinical practices to curtail complications should be targeted toward patients
      with preoperative anemia, weight loss, corticosteroid dependence, and toward
      those at risk for perioperative transfusions.

PMID- 28507885
TI  - Effect of Cervical Sagittal Balance on Laminoplasty in Patients With Cervical
      Myelopathy.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: We evaluated the
      relationship between cervical sagittal alignment parameters and clinical status
      in patients with cervical myelopathy and analyzed the effect of cervical sagittal
      balance on cervical laminoplasty. METHODS: Patients with cervical myelopathy (n =
      110) who underwent laminoplasty were included in this study. The relationship
      between cervical sagittal alignment parameters and clinical status was evaluated.
      The changes in radiographic cervical sagittal parameters and clinical status 2
      years after surgery were compared between patients with preoperative C2-7 SVA
      >=35 mm (group A) and those with preoperative C2-7 SVA <35 mm (group B). RESULTS:
      Preoperatively, C2-7 SVA had no correlation with defined health-related quality
      of life evaluation scores. At 2-year follow-up, the improvement in SF-36 physical
      component summary was significantly lower in group A than in group B. The
      postoperative change of C2-7 SVA did not significantly differ in 2 groups.
      Patients in group A maintained cervical regional balance after laminoplasty but
      experienced extensive postoperative neck pain. CONCLUSIONS: Our patients with a
      C2-7 SVA of >=35 mm maintained cervical regional balance after laminoplasty and
      their improvement in myelopathy was equivalent to that in patients with a C2-7
      SVA of <35 mm. However, the patents with a C2-7 SVA of >=35 mm experienced severe
      postoperative neck pain. C2-7 SVA is a parameter worth considering because it can
      lead to poor QOL and axial neck pain after laminoplasty.

PMID- 28507886
TI  - Racial Disparities in Elderly Patients Receiving Lumbar Spinal Stenosis Surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate for racial
      disparities in elderly patients having undergone lumbar spinal stenosis surgery.
      METHODS: The US Medicare Provider Analysis and Review database (records from 2005
      to 2011) was used to identify patients over the age of 65 years, diagnosed with
      lumbar spinal stenosis, and having undergone lumbar laminectomy or fusion
      surgery. Blacks were compared to Whites in both unmatched and propensity score
      matched populations. The data was analyzed with univariate (chi2 and Wilcoxon
      rank sum tests for unmatched comparison, and McNemar exact and signed rank sum
      tests for matched comparison) and multivariate models. RESULTS: Query of the data
      resulted in a study sample of 12 807 patients; 514 (4.0%) were identified as
      Black and 12 293 (96%) as White. Blacks were less likely to be discharged home
      (42.4% vs 58.9%, P < .0001) and had lower repeat operation rates (6.81% vs 11.5%,
      P = .0009); both remained significant in the propensity score-matched comparison.
      Finally, Blacks experienced more postoperative complications, higher median
      Medicare costs, but lower out-of-pocket expenses (P = .0113). Blacks had higher
      rates of diabetes (33.7% vs 21.5%, P < .0001) and obesity (9.92% vs 6.85%, P =
      .0074), when compared to Whites, but these comorbidities did not significantly
      affect odds of 30-day complications. CONCLUSIONS: Black patients having undergone
      lumbar spinal stenosis surgery were more likely to have received fusion at
      initial operation, had shorter pre- and postoperative follow-up intervals and
      displayed variances in discharge disposition. Reasons for these differences are
      not entirely understood; however, educational and socioeconomic factors and
      possibly ethnic/cultural biases may have contributed. Racial disparities in
      health care continue to be identified and should be further explored in order to
      eliminate them.

PMID- 28507887
TI  - Effectiveness of Operative and Nonoperative Care for Adult Spinal Deformity:
      Systematic Review of the Literature.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: There is a need for synthesizing data
      on effectiveness of treatments for patients with adult spinal deformity (ASD) due
      to its increasing prevalence and health care costs for these patients. The
      objective of this review was to estimate the effectiveness of surgery versus
      nonoperative care in patients with ASD. METHODS: A systematic review of articles
      in published in English using PubMed between 2005 and 2015. Surgical and
      nonsurgical series that reported baseline and follow-up health-related quality of
      life measures of patients with ASD with a minimum 2 years of follow-up were
      selected. Independent extraction of articles by 2 authors using predefined data
      fields, including risk of bias assessment. RESULTS: Surgery significantly reduces
      disability, pain, and improves patients' quality of life. The average
      postoperative improvement in Oswestry Disability Index was -19.1 (+/-9.0),
      Numerical Rating Scale back pain -4.14 (+/-1.38), Numerical Rating Scale leg pain
      -3.36 (+/-1.33), Short-Form Health Survey 36-SF36-Physical Component score 11.2
      (+/-5.07), and Short-Form Health Survey 36-Mental Component score 9.93 (+/-4.96).
      The complication rate ranged from 9.52% to 81.52% (mean = 39.62%), and the need
      for revision surgery ranged from 1.72% to 40.0% (mean = 15.71%). The best
      existing evidence about nonoperative care of ASD is provided from observational
      studies with very high risk of bias. Quantitative analyses of nonsurgical cohorts
      did not demonstrate significant changes in quality of life of patients after 2
      years of observation. CONCLUSIONS: This data may assist clinicians to counsel
      patients, as well as to inform health care providers and policymakers about what
      to expect from the treatment for ASD.

PMID- 28507889
TI  - Does parental support influence children's active school travel?
AB  - Today's 'backseat generation' of children is more often driven to school. Active
      school travel (AST) can contribute up to 30% of recommended daily physical
      activity. Although governed by a complex set of factors, parents are considered
      'gatekeepers' of children's travel mode decisions. Therefore, we investigate the
      relationship between parental support and children's AST. Data were from Active
      Streets, Active People-Junior (British Columbia, Canada). Children self-reported
      travel mode to/from school for 1 week (10 trips). We assessed parental perceived
      neighborhood traffic and crime safety (Neighborhood Environmental Walkability
      Scale-Youth) and frequency of parental support for AST (0-5 */week). We
      investigated the association between daily AST behaviour and parental support
      using logistic regression (controlling for age, sex, distance to school and
      perceived neighborhood safety). In our sample (n = 179, 11.0 +/- 1.0 years, 59%
      girls), 57% reported daily AST and 63% of parents provided daily support.
      Bivariate analyses showed AST behaviour was significantly associated with
      parental support frequency and parents' perceived safety. In adjusted analysis,
      daily parental support remained significantly associated with daily AST (OR 9.0,
      95% CI 4.2, 19.7). The relationship between parental support and AST was
      independent of noted correlates of AST. Thus, interventions that focus solely on
      changes to the built environment may not be enough to encourage AST. Therefore,
      interventions that aim to increase AST should involve parents and children in the
      planning process.

PMID- 28507888
TI  - Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of
      Caution.
AB  - STUDY DESIGN: A broad narrative review. OBJECTIVES: The objective of this article
      is to provide a technical review of spine stereotactic body radiotherapy (SBRT)
      planning and delivery, indications for treatment, outcomes, complications, and
      the challenges of response assessment. The surgical approach to spinal metastases
      is discussed with an overview of emerging minimally invasive techniques. METHODS:
      A comprehensive review of the literature was conducted on the techniques,
      outcomes, and developments in SBRT and surgery for spinal metastases. RESULTS:
      The optimal management of patients with spinal metastases is complex and requires
      multidisciplinary assessment from an oncologic team that is familiar with the
      shifting paradigm as a consequence of evolving techniques in surgery and
      stereotactic radiation, as well as new developments in systemic agents. The
      Spinal Instability Neoplastic Score and the epidural spinal cord compression
      (Bilsky) grading system are useful tools that facilitate communication among
      oncologic team members and can direct management by providing a baseline
      assessment of risks prior to therapy. The combined multimodality approach with
      "separation surgery" followed by postoperative spine SBRT achieves thecal sac
      decompression, improves tumor control, and avoids complications that may be
      associated with more extensive surgery. CONCLUSION: Spine SBRT is a highly
      effective treatment that is capable of delivering ablative doses to the target
      while sparing the critical organs-at-risk, chiefly the critical neural tissues,
      within a short and manageable schedule. At the same time, surgery occupies an
      important role in select patients, particularly with the expanding availability
      and expertise in minimally invasive techniques. With rapid adoption of spine SBRT
      in centers outside of the academic setting, it is imperative for the practicing
      oncologist to understand the relevance and application of these evolving
      concepts.

PMID- 28507890
TI  - Hand washing with soap and WASH educational intervention reduces under-five
      childhood diarrhoea incidence in Jigjiga District, Eastern Ethiopia: A community
      based cluster randomized controlled trial.
AB  - Despite the tremendous achievement in reducing child mortality and morbidity in
      the last two decades, diarrhoea is still a major cause of morbidity and mortality
      among children in many developing countries, including Ethiopia. Hand washing
      with soap promotion, water quality improvements and improvements in excreta
      disposal significantly reduces diarrhoeal diseases. The objective of this study
      was to evaluate the effect of hand washing with soap and water, sanitation and
      hygiene (WASH) educational Intervention on the incidence of under-five children
      diarrhoea. A community-based cluster randomized controlled trial was conducted in
      24 clusters (sub-Kebelles) in Jigjiga district, Somali region, Eastern Ethiopia
      from February 1 to July 30, 2015. The trial compared incidence of diarrhoea among
      under-five children whose primary caretakers receive hand washing with soap and
      water, sanitation, hygiene educational messages with control households.
      Generalized estimating equation with a log link function Poisson distribution
      family was used to compute adjusted incidence rate ratio and the corresponding
      95% confidence interval. The results of this study show that the longitudinal
      adjusted incidence rate ratio (IRR) of diarrhoeal diseases comparing
      interventional and control households was 0.65 (95% CI 0.57, 0.73) suggesting an
      overall diarrhoeal diseases reduction of 35%. The results are similar to other
      trials of WASH educational interventions and hand washing with soap. In
      conclusion, hand washing with soap practice during critical times and WASH
      educational messages reduces childhood diarrhoea in the rural pastoralist area.

PMID- 28507891
TI  - Discordance in perceived risk and epidemiological outcomes of prostate cancer
      among African American men.
AB  - As guidelines for prostate cancer screening have changed from an annual screening
      recommendation starting at age 50 to discussing the benefits and harms of
      screening with health care providers, it is necessary to examine other types of
      factors that are important to prostate cancer screening decisions among African
      American men. Perceived risk of developing cancer has been shown to predict
      cancer control behaviors and is lower among African Americans. We characterized
      perceived risk of developing prostate cancer among African American men from
      November 2009 to 2011 and evaluated the relationship between prostate cancer risk
      perceptions and sociodemographic characteristics, health care experiences, and
      knowledge and exposure to health information about cancer. Chi square tests and
      logistic regression were employed to determine independent associations. Overall,
      men did not believe they were at increased risk of developing prostate cancer;
      they believed their risk was equivalent to or lower than men the same age.
      Perceived risk of prostate cancer was associated with income (OR = 0.59, 95% CI =
      0.26, 1.34, p = 0.03), hypertension (OR = 2.68, 95% CI = 1.17, 6.16, p = 0.02),
      and beliefs about the association between race and cancer risk (OR = 2.54, 95% CI
      = 1.24, 5.20, p = 0.01). Clinic and community-based approaches to improve
      prostate cancer risk comprehension among African American men are needed to
      reduce the discordance between perceived risk and epidemiological data on
      prostate cancer risk factors. Risk education interventions that are developed for
      African American men may need to integrate information about susceptibility for
      multiple diseases as well as address strategies for risk reduction and
      prevention, and chronic disease management.

PMID- 28507893
TI  - Delayed diagnosis of severe tuberculous spondylodiscitis in an asylum seeker;
      patient or doctors delay?
AB  - The still increasing global migration affects the epidemiology of tuberculosis
      (TB) in European countries. We present the case of an asylum seeker from a TB
      high-endemic country, who presented with severe TB spondylodiscitis and need for
      emergency surgery. The patient had a history of recurrent sterile axillary and
      perianal abscesses for years, but TB was never properly ruled out. The patient
      underwent surgery, responded well to antibiotics and regained the ability to
      walk. After 6 month of treatment the patient was lost to follow-up. In light of
      the increasing migration from TB high-endemic countries to low-endemic countries,
      this case illustrates the paramount importance of minding TB as a differential
      diagnosis.

PMID- 28507892
TI  - A case of massive hemoptysis following transesophageal echocardiogram.
AB  - INTRODUCTION: Tracheal intubation leading to injury of the airway is a rare
      complication of transesophageal echocardiography (TEE). Tracheal trauma is not a
      described complication of TEE, and safety literature for this procedure remains
      silent on the matter. We describe the case of a patient on systemic
      anticoagulation and antiplatelet therapy who underwent TEE and suffered massive
      hemoptysis requiring bronchial artery embolization (BAE). CASE PRESENTATION: An
      elderly patient was admitted to the hospital with recently diagnosed atrial
      fibrillation and shortness of breath. The patient underwent a TEE with successful
      synchronized cardioversion on hospital day #2. Later that day the patient
      experienced respiratory distress and hemoptysis and was intubated. Oropharyngeal
      and gastrointestinal sources of bleeding were excluded. A bronchoscopy revealed
      active bleeding from an ulceration in the bronchus intermedius (BI) of the right
      lung. A 7 French Arndt endobronchial blocker (Cook Medical, Bloomington, Indiana)
      was placed and anticoagulation reversed. Bleeding stopped for two days, but then
      returned on hospital day #5, requiring BAE to the right bronchial artery. The
      procedure was successful, the patient was successfully extubated, and was
      discharged over the next 10 days. DISCUSSION: Massive hemoptysis and respiratory
      compromise as a result of tracheal trauma is not described in the TEE literature.
      This patient proved to be a difficult esophageal intubation secondary to a newly
      discovered Zenker's diverticulum. The risk for bleeding in this patient was
      higher secondary to anticoagulation with warfarin and antiplatelet therapy with
      ticagrelor. As in all cases of massive hemoptysis, key aspects of care in this
      case involved localization of bleeding, reversal of anticoagulation, and
      definitive management such as BAE. CONCLUSIONS: Tracheal trauma is not a
      described complication of TEE, but clinicians should be mindful of this possible
      complication in patients receiving anticoagulation. Typical management for
      massive hemoptysis was successful in this patient.

PMID- 28507894
TI  - Re-administration of abatacept for the control of articular symptoms of
      rheumatoid arthritis during anti-tuberculous therapy.
AB  - This case report describes the re-administration of abatacept to successfully
      reduce the articularsymptoms of a patient with rheumatoid arthritisduring the
      intensive phase of anti-tuberculous therapy. A 75-year-old man developed active
      pulmonary tuberculosis during the administration of abatacept for rheumatoid
      arthritis. The patient experienced a paradoxical reaction and exacerbation of
      rheumatoid arthritis that caused us to discontinue the abatacept. Later re
      administration of abatacept along with anti-tuberculosis treatment led to well
      controlled rheumatoid arthritis without exacerbation of the tuberculosis. This
      case shows that re-administration of abatacept may be much safer than TNF
      inhibitor to treat patients who are infected with mycobacteria during
      thetreatment of immunological diseases such asrheumatoid arthritiswith biological
      agents.

PMID- 28507897
TI  - Comparative analysis of microbial diversity in two hot springs of Bakreshwar,
      West Bengal, India.
AB  - Various aspects of hot springs at Bakreshwar (Lat. 23 degrees 52'48"N; Long. 87
      degrees 22'40"E) in West Bengal, India have been investigated since the middle of
      20th century, but comprehending the complete diversity and the complexity of the
      microbial population therein has been in the continuing process. Some of these
      microorganisms are found to have immense industrial importance. Microbes
      generally exist in milieus of varying complexities and diversities. Attempting
      the usually employed cultivation-based techniques in experimentation with those
      microbes had confronted various limitations. To overcome these limitations a
      strategy based on high-throughput sequencing of 16S rRNA gene amplicon analysis
      was employed for studying the differential diversity and the detailed nature of
      microbial population of the two hot springs of Bakreshwar (54  degrees C & 65 
      degrees C). Paired-end libraries of amplified V-3 hyper-variable 16S rDNA
      fragments from sets of samples that varied in their contents, ranging from a
      single bacterium to highly complex communities were sequenced. The comparison
      revealed the differential aspects in the two hot spring waters; the samples at 54
      degrees C showed the bacterial phylum Firmicutes (65.85%) and Synergistetes
      (27.24%) predominating and those from hot spring water at 65  degrees C showed
      the abundance of the phyla Firmicutes (96.10%) and Proteobacteria (3.36%). The
      presence of Archaea in the hot springs could not be ascertained.

PMID- 28507896
TI  - Intraoperative resection control using arterial spin labeling - Proof of concept,
      reproducibility of data and initial results.
AB  - OBJECTIVES: Intraoperative magnetic resonance imaging is a unique tool for
      visualizing structures during resection and/or for updating any kind of
      neuronavigation that might be hampered as a result of brain shift during surgery.
      Advanced MRI techniques such as perfusion-weighted imaging have already proven to
      be important in the initial diagnosis preoperatively, but can also help to
      differentiate between tumor and surgically induced changes intraoperatively.
      Commonly used methods to visualize brain perfusion include contrast agent
      administration and are therefore somewhat limited. One method that uses blood as
      an internal contrast medium is arterial spin labeling (ASL), which might
      represent an attractive alternative. MATERIALS AND METHODS: Ten healthy
      volunteers were examined using three different scanners and coils within 1 h (3T
      Achieva MRI using 32-channel head coil, 1.5T Achieva MRI using a 6-channel head
      coil, 1.5 Intera Scanner using 2 surface coils, Philips, Best, The Netherlands)
      and quantitative CBF values were calculated and compared between the different
      setups. Additionally, in eight patients with glioblastoma multiforme, ASL was
      used pre-, intra-, and postoperatively to define tumor tissue and the extent of
      resection in comparison to structural imaging. RESULTS: A high correlation (r =
      0.91-0.96) was found between MRI scanners and coils used. ASL was as reliable as
      conventional MR imaging if complete resection was already achieved, but
      additionally provided valuable information regarding residual tumor tissue in one
      patient. CONCLUSIONS: Intraoperative arterial spin-labeling is a feasible,
      reproducible, and reliable tool to map CBF in brain tumors and seems to give
      beneficial information compared to conventional intraoperative MR imaging in
      partial resection.

PMID- 28507895
TI  - Diverging volumetric trajectories following pediatric traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a significant public health concern, and can be
      especially disruptive in children, derailing on-going neuronal maturation in
      periods critical for cognitive development. There is considerable heterogeneity
      in post-injury outcomes, only partially explained by injury severity.
      Understanding the time course of recovery, and what factors may delay or promote
      recovery, will aid clinicians in decision-making and provide avenues for future
      mechanism-based therapeutics. We examined regional changes in brain volume in a
      pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time
      points. Children were first assessed 2-5 months post-injury, and again 12 months
      later. We used tensor-based morphometry (TBM) to localize longitudinal volume
      expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and
      26 well-matched healthy control children, also assessed twice over the same
      interval. In a prior paper, we identified a subgroup of msTBI patients, based on
      interhemispheric transfer time (IHTT), with significant structural disruption of
      the white matter (WM) at 2-5 months post injury. We investigated how this
      subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from
      msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The
      TBI-slow group had longitudinal decreases in brain volume in several WM clusters,
      including the corpus callosum and hypothalamus, while the TBI-normal group showed
      increased volume in WM areas. Our results show prolonged atrophy of the WM over
      the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows
      a different pattern that could indicate a return to a healthy trajectory.

PMID- 28507899
TI  - Unusual embolization of a pacemaker lead fragment during lead extraction.

PMID- 28507900
TI  - Direct visualization of an atrial transseptal left ventricular endocardial lead
      implantation within an isolated heart.

PMID- 28507898
TI  - Optically and acoustically triggerable sub-micron phase-change contrast agents
      for enhanced photoacoustic and ultrasound imaging.
AB  - We demonstrate a versatile phase-change sub-micron contrast agent providing three
      modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound
      contrast with optical activation, and 3) ultrasound contrast with acoustic
      activation. This agent, which we name 'Cy-droplet', has the following novel
      features. It comprises a highly volatile perfluorocarbon for easy versatile
      activation, and a near-infrared optically absorbing dye chosen to absorb light at
      a wavelength with good tissue penetration. It is manufactured via a 'microbubble
      condensation' method. The phase-transition of Cy-droplets can be optically
      triggered by pulsed-laser illumination, inducing photoacoustic signal and forming
      stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively,
      Cy-droplets can be converted to microbubble contrast agents upon acoustic
      activation with clinical ultrasound. Potentially all modes offer extravascular
      contrast enhancement because of the sub-micron initial size. Such versatility of
      acoustic and optical 'triggerability' can potentially improve multi-modality
      imaging, molecularly targeted imaging and controlled drug release.

PMID- 28507901
TI  - Use of intracardiac echocardiography as a guide during interventricular septum
      puncture in a patient undergoing cardiac resynchronization therapy.

PMID- 28507902
TI  - An unusual ICD shock: What is the mechanism?

PMID- 28507903
TI  - High-output heart failure due to subclavian vessel fistula as a late complication
      following implantation of a biventricular pacemaker.

PMID- 28507904
TI  - Electroanatomical voltage mapping of atrial Mahaim potentials to guide catheter
      ablation.

PMID- 28507905
TI  - Gastric syphilis.
AB  - Syphilis is a chronic systemic infectious disease. Gastric involvement is
      uncommon. We report of a 55-year-old female patient with a history of epigastric
      pain and a diagnosis of Syphilis confirmed by main clinical symptoms, tolulized
      red unheated serum test(TRUST) and treponema pallidum hemagglutination
      assay(TPHA). At the same time, we still reported gastric involvement about
      syphilis in this patient with gastroscopy and pathology.

PMID- 28507907
TI  - Effectiveness of enzyme replacement therapy in Fabry disease: Long term
      experience in Argentina.
AB  - : Evidence regarding long term effectiveness of enzyme replacement therapy (ERT)
      in Fabry disease (FD) is needed. The aim of this study was to analyze in a cohort
      of FD patients in Argentina, the long term effectiveness of ERT on renal, cardiac
      and cerebrovascular parameters. METHODS: Patients with genetically proven FD were
      included from GADYTEF (Argentinean group for the treatment of FD) between 2001
      and 2014. Renal, cardiac, and cerebral outcomes were prospectively studied in
      patients treated with ERT. Additionally, the occurrence of major cardiac
      complications, stroke, end-stage renal disease and death was analyzed during
      follow up. RESULTS: During the follow-up 8 major complications occurred in 5
      patients (n = 2 deaths, n = 4 cases of end stage renal disease and n = 1 atrial
      fibrillation), 4 of them males and only 1 female who suffered an atrial
      fibrillation. Sudden death or stroke did not occur. Four (40%) of 10 males with
      baseline left ventricular hypertrophy (LVH) reduced left ventricular mass index
      (LVMI) from 163.1 +/- 64.7 to 123.4 +/- 49.8 g/m2, 2 stabilized LVMI and 4
      increased LVMI from157.9 +/- 32.3 to 261.6 +/- 48.6 g/m2. Estimated glomerular
      filtration was stable in 30 patients (17 males and 13 females). CONCLUSIONS: We
      observed a few major complications during the follow up. Future studies are
      necessary to show the effectiveness of ERT in affected patients.

PMID- 28507906
TI  - A case of a positive coccidioides stool culture in an immunocompetent patient
      with disseminated coccidioidomycosis.
AB  - Coccidioidomycosis (CM) is an infection caused by the coccidioides fungus. The
      spectrum of the disease ranges from a mild upper respiratory illness to severe
      disseminated infection that could affects the bones, joints, skin, central
      nervous system, and the gastrointestinal tract. Previous reports of a positive
      stool culture in the setting of disseminated CM are extremely rare. Herein, we
      describe a case of a 43-year-old immunocompetent patient with disseminated CM and
      evidence of positive coccidioides stool culture.

PMID- 28507908
TI  - Renal Cell Carcinoma in a Pregnant Woman With Horseshoe Kidney.
AB  - To our knowledge, this is the first reported case of renal cell carcinoma in
      kidney horseshoe diagnosed in the second trimester of pregnancy. We performed
      open radical nephrectomy when the pregnancy was completed. Kidney cancer is rare
      during pregnancy and the symptoms can be mimic urinary infection. The diagnosis
      and its management can be a challenge.

PMID- 28507909
TI  - Open Vesicocalicostomy for the Management of Transplant Ureteral Stricture.
AB  - A 59-year-old male developed a proximal stricture of his transplant ureter ten
      years after a living donor renal transplant. Endoscopic management was
      unsuccessful, and the patient was temporized with percutaneous nephrostomy tubes
      for months. Eventually, it became clear he would require surgical revision.
      Intraoperatively, complete fibrosis of the renal hilum, and intrarenal location
      of the pelvis precluded the planned pyelovesicostomy. A successful open
      vesicocalicostomy was performed, anastomosing a bladder flap to a lower pole
      calix. The patient remains recurrence free after 6 months of follow-up.

PMID- 28507910
TI  - Penile Calciphylaxis: The Use of Radiological Investigations in the Management of
      a Rare and Challenging Condition.
AB  - Penile calciphylaxis is a rare phenomenon of penile necrosis observed in patients
      with hemodialysis-dependent end-stage renal failure. Multiple treatments have
      been proposed including conservative management, surgical debridement and
      penectomy; yet, the prognosis remains extremely poor. Here, we describe a patient
      with protracted resolution of dry gangrene of the glans, which failed
      conservative management of wound care and pain management. Radiological studies
      revealed extensive calcification of abdominal aorta and branching vessels
      including the penile arteries. Due to intolerable pain, the patient required
      total penectomy. Earlier surgical intervention guided by findings on radiological
      studies may improve quality of life in this population.

PMID- 28507911
TI  - Filariasis Orchitis-Differential for Acute Scrotum Pathology.
AB  - Granulomatous Orchitis secondary to lymphatic filiarisis is a rare diagnosis
      within the United States. We report a case of a 22yo Male from Sri Lanka, with a
      new onset scrotal swelling and palpable right testicular mass. Ultrasound
      identified a 1 cm right testicular mass with signs of tunica albuginea invasion.
      A right inguinal radical orchiectomy was performed and pathology showed Filarial
      orchitis. This report describes the detailed history, physical exam, and
      diagnostic workup and treatment options for a rare entity for acute scrotal
      pathology.

PMID- 28507912
TI  - Preparation, characterization and antibacterial activity of chitosan and
      phosphorylated chitosan from cuttlebone of Sepia kobiensis (Hoyle, 1885).
AB  - Chitosan is a commercially available derivative of chitin that has been
      extensively studied for its antimicrobial properties. In order to improve the
      water solubility and its biological activity, the chemical modification or
      derivatisation is attempted. In the present investigation, the chitosan prepared
      from the cuttlebone of Sepia kobiensis was being chemically modified by reacting
      it with orthophosphoric acid so as to obtain phosphorylated chitosan. Then the
      chitosan and phosphorylated chitosan were structurally characterized through FT
      IR spectroscopy. Further the antibacterial activity of chitosan and
      phosphorylated chitosan was tested against clinically isolated human pathogens
      (Gram-positive: Streptococcus sp., Streptococcus pneumoniae and Staphylococcus
      aureus and Gram-negative: Escherichia coli, Vibrio cholerae, V. alginolyticus,
      Vibrio parahaemolyticus, Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Salmonella sp. and Proteus vulgaris) by well diffusion method and the Minimum
      Inhibitory Concentration (MIC) was also calculated. The results of the present
      study suggests that the chitosan and phosphorylated chitosan has concentration
      dependent antibacterial activity with variation against several pathogenic human
      pathogenic bacterial strains which indicates their possible use as antibacterial
      agents.

PMID- 28507915
TI  - Smoking in Renal Transplantation; Facts Beyond Myth.
AB  - Smoking is one of the preventable leading causes of death worldwide. Most of the
      studies focused on the association between smoking and cardiovascular disease,
      pulmonary diseases, malignancy and death. However, the direct effect of smoking
      on the renal system was undermind. There are emerging evidence correlating
      tobacco use with pathological changes in the normal kidneys. The effect is more
      obvious on the renal allograft most probably due to the chronic immune
      suppression status and the metabolic effect of the drugs. Several studies have
      documented a deleterious effect of smoking on the renal transplant recipients.
      Smoking was associated with lowering patient and graft survival. Smoking
      cessation proved to improve graft survival and to a lesser extent recipient
      survival. Even receiving a renal transplant from a smoker donor increases the
      risk of death for the recipient and carries a poorer graft survival compared to
      non-smoking donors. Most of the studies investigating the effect of smoking were
      based on self-reporting questioners, which may be misleading due to poor recall
      or the desire to give socially acceptable answers. This made the need of a
      reliable biomarker of ultimate importance. Cotinine was proposed as a promising
      biomarker that may help to provide objective evidence regarding the status of
      smoking and the dose of nicotine exposure, yet there are still some limitations
      of its use. The aim of this work is to review the current evidence to improve our
      understanding of this critical topic. Indeed, this will help to guide better
      designed studies in the future.

PMID- 28507913
TI  - Role of gastroesophageal reflux disease in lung transplantation.
AB  - Lung transplantation is one of the highest risk solid organ transplant
      modalities. Recent studies have demonstrated a relationship between
      gastroesophageal reflux disease (GERD) and lung transplant outcomes, including
      acute and chronic rejection. The aim of this review is to discuss the
      pathophysiology, evaluation, and management of GERD in lung transplantation, as
      informed by the most recent publications in the field. The pathophysiology of
      reflux-induced lung injury includes the effects of aspiration and local
      immunomodulation in the development of pulmonary decline and histologic
      rejection, as reflective of allograft injury. Modalities of reflux and esophageal
      assessment, including ambulatory pH testing, impedance, and esophageal manometry,
      are discussed, as well as timing of these evaluations relative to
      transplantation. Finally, antireflux treatments are reviewed, including medical
      acid suppression and surgical fundoplication, as well as the safety, efficacy,
      and timing of such treatments relative to transplantation. Our review of the data
      supports an association between GERD and allograft injury, encouraging a strategy
      of early diagnosis and aggressive reflux management in lung transplant recipients
      to improve transplant outcomes. Further studies are needed to explore additional
      objective measures of reflux and aspiration, better compare medical and surgical
      antireflux treatment options, extend follow-up times to capture longer-term
      clinical outcomes, and investigate newer interventions including minimally
      invasive surgery and advanced endoscopic techniques.

PMID- 28507916
TI  - Past, present and future of kidney paired donation transplantation in India.
AB  - One third of healthy willing living kidney donors are rejected due to ABO blood
      group incompatibility and donor specific antibody. This increases pre-transplant
      dialysis duration leading to increased morbidity and mortality on the kidney
      transplantation waiting list. Over the last decade kidney paired donation is most
      rapidly increased source of living kidney donors. In a kidney transplantation
      program dominated by living donor kidney transplantation, kidney paired donation
      is a legal and valid alternative strategy to increase living donor kidney
      transplantation. This is more useful in countries with limited resources where
      ABO incompatible kidney transplantation or desensitization protocol is not
      feasible because of costs/infectious complications and deceased donor kidney
      transplantation is in initial stages. The matching allocation, ABO blood type
      imbalance, reciprocity, simultaneity, geography were the limitation for the
      expansion of kidney paired donation. Here we describe different successful ways
      to increase living donor kidney transplantation through kidney paired donation.
      Compatible pairs, domino chain, combination of kidney paired donation with
      desensitization or ABO incompatible transplantation, international kidney paired
      donation, non-simultaneous, extended, altruistic donor chain and list exchange
      are different ways to expand the donor pool. In absence of national kidney paired
      donation program, a dedicated kidney paired donation team will increase access to
      living donor kidney transplantation in individual centres with team work. Use of
      social networking sites to expand donor pool, HLA based national kidney paired
      donation program will increase quality and quantity of kidney paired donation
      transplantation. Transplant centres should remove the barriers to a broader
      implementation of multicentre, national kidney paired donation program to further
      optimize potential of kidney paired donation to increase transplantation of O
      group and sensitized patients. This review assists in the development of similar
      programs in other developing countries.

PMID- 28507914
TI  - Intra-islet endothelial cell and beta-cell crosstalk: Implication for islet cell
      transplantation.
AB  - The intra-islet microvasculature is a critical interface between the blood and
      islet endocrine cells governing a number of cellular and pathophysiological
      processes associated with the pancreatic tissue. A growing body of evidence
      indicates a strong functional and physical interdependency of beta-cells with
      endothelial cells (ECs), the building blocks of islet microvasculature. Intra
      islet ECs, actively regulate vascular permeability and appear to play a role in
      fine-tuning blood glucose sensing and regulation. These cells also tend to behave
      as "guardians", controlling the expression and movement of a number of important
      immune mediators, thereby strongly contributing to the physiology of islets. This
      review will focus on the molecular signalling and crosstalk between the intra
      islet ECs and beta-cells and how their relationship can be a potential target for
      intervention strategies in islet pathology and islet transplantation.

PMID- 28507917
TI  - Systemic meta-analysis assessing the short term applicability of early conversion
      to mammalian target of rapamycin inhibitors in kidney transplant.
AB  - AIM: To consolidate the present evidence of effectiveness in renal functioning
      and graft survival following early introduction of mammalian target of rapamycin
      (mTOR) inhibitors with or without calcineurin inhibitors (CNIs) in renal
      transplant recipients. METHODS: We analysed the current literature following
      PROSPERO approval describing the role of immunosuppressive agent, mTOR inhibitors
      as an alternative to CNI within six months of renal transplant by searching the
      PubMed, EMBASE, Cochrane, Crossref, and Scopus using MeSH terms. RESULTS: Six
      articles of early withdrawal of CNI and introduction of mTOR-inhibitors within
      six months of renal transplantation were sought. Glomerular filtration rate (GFR)
      and serum creatinine were significantly better in mTOR inhibitor group with
      equivalent survival at 12 mo, even though Biopsy Proven Acute rejection was
      significantly higher in mTOR-inhibitor group. CONCLUSION: The evidence reviewed
      in this meta-analysis suggests that early introduction mTOR-inhibitors
      substantial CNI minimization. The mTOR inhibitors such as everolimus and
      sirolimus, due to their complementary mechanism of action and favourable
      nephrotoxicity profile; better glomerular filtration, lower serum creatinine with
      equivalent survival. Having said that, due to the higher rejection rate, may
      influence the use of these regimens to patients with moderate to high
      immunological risk patients.

PMID- 28507918
TI  - Living related and living unrelated kidney transplantations: A systematic review
      and meta-analysis.
AB  - AIM: To compare the outcomes between related and unrelated kidney
      transplantations. METHODS: Literature searches were performed following the
      Cochrane guidelines. We conducted a systematic review and a meta-analysis, which
      included 12 trials that investigated outcomes including the long-term (ten
      years), mid-term (one to five years), and short-term (one year) graft survival
      rate as well as the acute rejection rate. Meta-analyses were performed using
      fixed and random-effects models, which included tests for publication bias and
      heterogeneity. RESULTS: No difference in graft survival rate was detected in
      patients who underwent living related kidney transplantations compared to
      unrelated (P = 0.44) transplantations after ten years. There were no significant
      differences between the graft survival rate in living related and unrelated
      kidney transplantations after a short- and mid-term follow-up (P = 0.35, P =
      0.46). There were no significant differences between the acute rejection rate in
      living related and unrelated kidney transplantations (P = 0.06). CONCLUSION: The
      long, mid and short term follow-up of living related and unrelated kidney
      transplantation showed no significant difference in graft survival rate. Also,
      acute rejection rate was not significantly different between groups.

PMID- 28507919
TI  - Hepatitis C Virus RNA Strands Detection in Peripheral Blood Mononuclear Cells
      Legitimizes Virus Eradication in Negative Serum PCR Naive and Post-treatment
      Patients.
AB  - Background and Aims: Hepatitis C virus (HCV) hepatotropism is associated with
      intra-peripheral blood mononuclear cell (PBMC) infection that causes post
      treatment relapse in RNA seronegative patients. Our understanding of the
      association of non-viremic hepatic fibrosis with positive anti-HCV IgG antibodies
      and active hepatocellular damage might be increased by PBMCs screening for
      intracellular infection. Thus, the goals of this study included evaluation of
      PBMCs PCR for diagnosing HCV infection, addressing PBMCs plus serum real-time
      (SRT) PCR benefits over SRT-PCR alone, studying intra-PBMCs distribution of RNA
      sense and antisense strands, and identifying treatment feasibility in solitary
      intracellular infection. Methods: Enzyme-linked immunosorbent assay, SRT-PCR and
      PBMCs PCR were used to evaluate HCV infection in 401 subjects. The patients were
      classified into groups of negative controls (n = 30), positive controls (n = 63),
      non-viremia post-treatment (experienced; n = 166) and naive (n = 49) cases, and
      non-viremia positive PBMCs PCR naive (n = 35) and experienced (n = 58) patients.
      Results: The diagnosis of true positive and negative by PBMCs PCR and SRT-PCR had
      100% and 96.7% compatibility respectively. PBMCs PCR detected intracellular HCV
      infection in 49 out of 215 non-viremia patients; among them, naive cirrhotics had
      significantly higher number of intracellular infection than the naive non
      cirrhotic (p < 0.001) and experienced patients (p < 0.0001). Antisense and sense
      strands were respectively recognized in naive and experienced cases (p =
      0.01218). Intracellular HCV strands were detected in 18.02% of experienced
      patients. Recognition of intracellular RNA strands showed significant decline in
      experienced compared to naive patients (p < 0.05). Conclusion: PBMCs PCR is a
      valid diagnostic test that can diagnose intracellular HCV when SRT-PCR is
      negative. Antisense and sense strands are respectively recognized more often in
      naive and experienced patients. The expected overall relapsing rate in our cohort
      was 18.02%. Intra-PBMC infections are associated with liver cirrhosis in naive
      non-viremia patients. Eradication of intracellular strands is recommended to
      avoid RNA seroconversion. Ethical approval certificate: Registration number
      10231.

PMID- 28507920
TI  - Passenger Lymphocyte Syndrome (PLS): A Single-center Retrospective Analysis of
      Minor ABO-incompatible Liver Transplants.
AB  - Background and Aims: Due to the shortage of donor livers, minor ABO-incompatible
      liver transplantations are commonly performed. Together with the allograft,
      immunocompetent B-lymphocytes, called passenger lymphocytes, are transplanted. In
      case of minor ABO-incompatibility, these passenger lymphocytes produce antibodies
      directed towards the recipient's red blood cells, which causes immune-mediated
      hemolysis, also known as the passenger lymphocyte syndrome (PLS). Although this
      is a self-limiting disorder, serious complications can occur, including graft
      failure. Retrospectively, we evaluated the role of PLS in minor ABO-incompatible
      liver transplantations performed at our center. Methods: A retrospective analysis
      was conducted for all minor ABO-incompatible liver transplantations performed at
      the Antwerp University Hospital between 2003 and 2015. All patient files were
      inspected for clinical and laboratory findings. In cases of PLS diagnosis, the
      applied treatment was also studied. Results: In total, 10 patients underwent a
      minor ABO-incompatible liver transplantation and 4 showed signs of PLS. All 4 PLS
      patients were treated with different therapeutic strategy, corresponding to the
      severity of hemolysis. In all 4 cases, PLS resolved following treatment.
      Conclusion: When performing minor ABO-incompatible liver transplantations,
      knowledge of PLS is elemental. Next to a high index of clinical suspicion, we
      suggest routine screening for markers of hemolysis, with emphasis on haptoglobin
      level and direct antiglobulin test, weekly in the first 4 weeks post
      transplantation as well as in case of a sudden hemoglobin drop within the first 3
      months after transplantation. Peri- and postoperative transfusion support using
      donor-compatible blood has been suggested to prevent the occurrence or limit the
      extent of hemolysis.

PMID- 28507921
TI  - Sofosbuvir-based Regimens with Task Shifting Is Cost-effective in Expanding
      Hepatitis C Treatment Access in the United States.
AB  - Background and Aims: The current paradigm of specialist physician-managed
      treatment of chronic hepatitis C virus infection (HCV) is inefficient in
      absorbing the approximately 3 million patients awaiting treatment in the United
      States. Task shifting-whereby specialist physicians screen patients for treatment
      eligibility but on-treatment monitoring is devolved to more abundant non
      physician clinicians-achieves non-inferior treatment outcomes with second
      generation direct-acting antivirals (2nd Gen DAAs), may increase treatment
      capacity, and may facilitate greater treatment access. We determined the cost
      effectiveness of 2nd Gen DAAs with respect to interferon-based first-generation
      DAAs (1st Gen DAAs) within a task-shifted treatment model. Methods: Using a
      previously described decision-analytic Markov structure, we modeled a
      hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a
      lifetime horizon, based upon our outreach clinic's HCV treatment protocol.
      Treatment-naive and treatment-experienced HCV cohorts were modeled separately,
      based upon our outr8each clinic's demographics. Treatment response to 2nd Gen
      DAAs was modeled based on our outreach clinic's data. Adverse events, utility,
      costing, and transition probabilities were sourced from the literature. Results:
      Driven by improved effectiveness and safety, as well as an expected increase in
      treatment capacity, 2nd Gen DAAs treatment monitored by non-physician clinicians
      was projected to improve health outcomes and be dominant from a cost-effective
      perspective versus that of 1st Gen DAAs. Trends were consistent across all
      assessed patient subpopulations. Conclusions: Based on an assumption of increased
      treatment capacity accompanying a task-shifted treatment model, 2nd Gen DAAs
      based treatment was cost effective and cost saving as compared to 1st Gen DAAs
      based treatment for all HCV patient subgroups assessed.

PMID- 28507922
TI  - Sofosbuvir Use in the Setting of End-stage Renal Disease: A Single Center
      Experience.
AB  - Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal
      disease (ESRD) who are dialysis-dependent form a unique group, in which safety,
      tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals
      (DAAs) need further evaluation. Methods: We performed a retrospective analysis of
      14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based
      therapy. We evaluated dose escalation to standard-dose SOF in this proof-of
      principle experience. Results: Sustained virological response (defined as
      undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15
      (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as
      conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15
      treatment courses, patients completed the designated treatment duration. One
      patient was treated twice and developed SVR-12 with the retreatment. One patient
      was lost to follow-up and counted as a non-responder. Premature discontinuations
      were not due to DAA-related adverse effects. There were no reports of severe
      adverse effects or drug interactions. Conclusion: We treated CHC patients with
      ESRD using dose escalation to standard-dose SOF in this proof-of-principle
      experience and achieved SVR rates comparable to general population.

PMID- 28507923
TI  - Phenotypes and Chronic Organ Damage May Be Different among Siblings with Wilson's
      Disease.
AB  - Background and Aims: Cloning of ATP7B provided evidence that Wilson's disease is
      a hepatic copper toxicosis with a variety of extrahepatic complications. Affected
      siblings with the same genetic background and exposure to similar environmental
      factors may be a good model for the study of genotype-phenotype correlation.
      Methods: Twenty-three affected siblings in 11 families were selected from a
      database. The first phenotypes were determined according to the international
      proposal. The final types of chronic organ damage were re-evaluated for life-long
      management. Results: Phenotypes were identical in 5 of the families and different
      in 6 of the families. The acute hepatic phenotype H1 was found in 3 younger
      siblings and 1 older sibling. All survived an acute episode of hemolysis with
      underlying chronic liver disease. One also presented complication with
      neurological disease. The neurological phenotype N1 with neuropsychiatric
      symptoms and hepatic disease was found in 2 aged siblings of 1 family, in an
      older sibling in 3 families and in the oldest sibling in 1 family. Phenotypes in
      siblings were mainly split by either H1 occurring in random order or age
      dependent N1. Types of chronic organ damage were identical in 8 of the families
      and different in 3 of the families. The same combination of chronic liver disease
      was found in 6 families and chronic liver disease complicated with neurological
      disease in 2 families. Split organ damage in siblings was found when an older
      sibling was complicated by neurological disease. There was no reverse combination
      of a younger sibling being complicated by neurological disease in any of the
      families. Conclusion: Phenotype combinations of siblings were mainly modified by
      externally-induced hemolytic episodes, while chronic organ damage in siblings was
      split by age-dependent neurological complications.

PMID- 28507924
TI  - Improved Outcomes Following Hepatocellular Carcinoma (HCC) Diagnosis in Patients
      Screened for HCC in a Large Academic Liver Center versus Patients Identified in
      the Community.
AB  - Background and Aims: Hepatocellular carcinoma (HCC) is the sixth most commonly
      occurring cancer worldwide. Knowledge and adherence to HCC surveillance
      guidelines has been associated with earlier detection. We sought to evaluate
      characteristics and outcomes following HCC diagnosis in patients screened for HCC
      in a large academic liver center versus patients diagnosed and referred from the
      community. Methods: We reviewed the records of patients diagnosed with HCC in the
      liver center of an academic institution from January 1999 till December 2013.
      Patients were classified into two groups: patients followed in our hepatology
      clinic and patients with HCC recently referred to our center. Univariate analysis
      was performed using chi-squared test and multivariate analysis was performed
      using SPSS 22.0. Results: The records of 410 patients were reviewed, and included
      77.3% of patients referred from the community and 22.7% of patients followed in
      our clinic. In the clinic group, 75.6% were identified with one nodule at initial
      diagnosis, compared to 65.6% in the referral group. Patients in the referral
      group were more likely to present with tumors >=5 cm at diagnosis, with 28.7%
      compared to 5.4% in the clinic group (p < 0.0001). Patients referred from the
      community were also less likely to undergo transplant, with 32.2% as compared to
      48.4% of the clinic group (p < 0.004). Conclusion: Patients with chronic liver
      disease managed in an academic liver center present in the early stage of HCC
      diagnosis and are more likely to meet the Milan criteria and undergo transplant.
      Early referral to a specialized transplant center, if feasible, where a
      multidisciplinary approach is utilized might be essential in the management of
      chronic liver disease.

PMID- 28507925
TI  - Stratified Platelet-to-lymphocyte Ratio: A Novel Target for Prognostic Prediction
      of Hepatocellular Carcinoma after Curative Liver Resection.
AB  - Background and Aims: Platelet-to-lymphocyte ratio (PLR) has been shown to predict
      prognosis of cancers. We aimed to evaluate the prognostic value of stratification
      of PLR in patients after curative liver resection (CLR) for hepatocellular
      carcinoma (HCC). Methods: A total of 1804 patients who underwent CLR for
      suspected HCC between January 2007 and January 2014 were screened for the study.
      All of the patients were categorized into equal tertiles according to the number
      of patients and the distribution of PLR. Prognostic significance was determined
      for overall survival (OS) and was assessed using Kaplan-Meier analysis.
      Univariate and multivariate Cox proportional hazard regression analyses were
      evaluated for association of all independent parameters with disease prognosis.
      Results: The optimal cut-off points of preoperative PLR were: (T1) 11.98-75.00,
      (T2) 75.00-113.33 and (T3) 113.33-567.50. There were obvious differences in each
      PLR tertile with mortality within 36 months of CLR (plog-rank < 0.001).
      Multivariable analysis suggested that the level of PLR (HR = 1.004, 95%CI: 1.001
      1.008, p = 0.006), portal vein thrombosis (HR = 3.406, 95%CI: 1.185-9.794, p =
      0.023), number of nodules (HR = 1.810, 95%CI: 1.345-2.437, p < 0.001), Child
      Turcotte-Pugh score (HR = 1.741, 95%CI: 1.129-2.684, p = 0.012) and microvascular
      invasion (HR = 2.730, 95%CI: 1.777-4.196, p < 0.001) were significant predictors
      of mortality. Kaplan-Meier analysis of overall survival (OS) demonstrated that
      each PLR tertile showed a progressively worse OS and apparent separation (plog
      rank = 0.016). The highest 5-year OS rate following CLR (58%) was revealed in
      tertile 1. In contrast, the lowest 5-year OS rate (30%) was revealed in tertile
      3. Conclusion: Stratified preoperative PLR could strengthen the predictive power
      for OS in HCC patients with CLR.

PMID- 28507926
TI  - Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct
      acting Antivirals.
AB  - Background and Aims: The lack of specificity has limited the role of serum alpha
      fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients
      with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine
      whether AFP may decrease after achieving a sustained virological response (SVR)
      in patients with HCV-related cirrhosis. Methods: We performed a retrospective
      study of patients with HCV-related cirrhosis who were cured with direct-acting
      antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory
      values, including serum AFP, were measured before and after completing the DAA
      treatment. Results: Fifty-six patients met the inclusion criteria, with median
      (interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male.
      All patients received DAA therapy without interferon. AFP decreased from median
      (IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of
      treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model
      for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase
      (AST) to platelet ratio index (APRI) scores at baseline were not significantly
      associated with AFP reduction. On multivariate analysis, platelet count, AST and
      total bilirubin at baseline were significantly correlated to AFP reduction (p =
      0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the
      reduction in AFP. There was no statistically significant correlation between
      baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant
      decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a
      reduction in AFP after DAA treatment, AFP should be further studied as a
      screening modality for HCC in patients with cirrhosis.

PMID- 28507928
TI  - The Role of Direct-acting Antivirals in the Treatment of Children with Chronic
      Hepatitis C.
AB  - In the United States, chronic infection with the hepatitis C virus (HCV) affects
      an estimated 0.1-2% of the pediatric population, who are consequently at risk for
      major complications, including cirrhosis, hepatocellular carcinoma, and death.
      The current standard of treatment for chronic hepatitis C (CHC) in children is
      pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG
      IFN/ribavirin therapy is approved for children ages 3 and older; however, it is
      often held from use until adulthood because of its extensive list of potential
      side effects and high likelihood of causing adverse symptoms. While CHC is
      usually indolent in children and adolescents, immediately treating and curbing
      the spread of HCV before adulthood is important, as there can be transmission to
      other individuals via sexual activity and infected females can later vertically
      transmit the infection during pregnancy, the latter representing the most common
      means of transmission for children in the United States. The recent development
      of direct-acting antivirals has shown promising results in clinical trials for
      use in children and has dramatically increased the rates of sustained virological
      response in adults while improving side effect profiles as compared to interferon
      based treatments. Given the usually indolent course of CHC in children,
      significant side effects of the currently-approved PEG-IFN/ribavirin therapy, and
      likely availability of all-oral interferon-free regimens for children within a
      few years, deferring treatment in clinically-stable children with CHC in
      anticipation of upcoming superior treatment modalities may be justified.

PMID- 28507927
TI  - Immune Dysfunction in Cirrhosis.
AB  - Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body.
      Cirrhosis-associated immune dysfunction leads to alterations in both innate and
      acquired immunity, due to defects in the local immunity of liver as well as in
      systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic
      phenomenon, comprised of both increased systemic inflammation and
      immunodeficiency, and is responsible for 30% mortality. It also plays an
      important role in acute as well as chronic decompensation. Immune paralysis can
      accompany it, which is characterized by increase in anti-inflammatory cytokines
      and suppression of proinflammatory cytokines. There is also presence of increased
      gut permeability, reduced gut motility and altered gut flora, all of which leads
      to increased bacterial translocation. This increased bacterial translocation and
      consequent endotoxemia leads to increased blood stream bacterial infections that
      cause systemic inflammatory response syndrome, sepsis, multiorgan failure and
      death. The gut microbiota of cirrhotic patients has more pathogenic microbes than
      that of non-cirrhotic individuals, and this disturbs the homeostasis and favors
      gut translocation. Prompt diagnosis and treatment of such infections are
      necessary for better survival. We have reviewed the various mechanisms of immune
      dysfunction and its consequences in cirrhosis. Recognizing the exact
      pathophysiology of immune dysfunction will help treating clinicians in avoiding
      its complications in their patients and can lead to newer therapeutic
      interventions and reducing the morbidity and mortality rates.

PMID- 28507931
TI  - Tranilast Can be a Useful Addition to the Limited Anti-Epidermolysis Bullosa
      Weaponry.

PMID- 28507930
TI  - Non-alcoholic Fatty Liver Disease in South Asians: A Review of the Literature.
AB  - Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
      (NASH) are national and global epidemics. The disease is characterized by a
      spectrum of liver steatosis (fat deposition), inflammation (in NASH) and
      fibrosis. NAFLD and specifically NASH can lead to cirrhosis, which carry risks of
      progression to portal hypertension and hepatocellular carcinoma (HCC). NASH is
      also associated with higher mortality from cardiovascular causes. Most of the
      data for NAFLD has been obtained from the perspective of developed nations,
      although the disease is increasing and threatening to reach epidemic proportions
      across the world. Emerging data is notable for high prevalence of NAFLD in South
      Asian populations, presumably resulting from a combination of underlying genetic
      polymorphisms and changes in socio-economic status. It is also notable that an
      'Asian Paradox' has been defined for NAFLD based upon the observation of lower
      than pre-defined body mass index (BMI), otherwise termed as "lean NAFLD", among
      this population. Yet, data remains limited in regards to the characteristics of
      NAFLD/NASH in this population. In this article, we present a review of the
      literature and discuss the prevalence, associated risk factors and burden of HCC
      in South Asians with NAFLD.

PMID- 28507929
TI  - Perspectives on Nonalcoholic Fatty Liver Disease: An Overview of Present and
      Future Therapies.
AB  - Nonalcoholic fatty liver disease (NAFLD) represents a major public health
      epidemic. Pharmacologic therapies for this condition are scarce, but multiple
      agents with novel mechanisms of action are in development. Here we review the
      pathophysiology and natural history of NALFD, diagnostic testing and data for
      currently available treatment strategies. We then turn our attention to promising
      developmental drugs and their respective trials. As the prevalence of fatty liver
      disease increases, clinicians will have more tools at hand for management of this
      condition. We conclude the horizon is bright for patients and doctors who deal
      with NAFLD.

PMID- 28507932
TI  - Application of Various Types of Liposomes in Drug Delivery Systems.
AB  - Liposomes, due to their various forms, require further exploration. These
      structures can deliver both hydrophilic and hydrophobic drugs for cancer,
      antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines,
      enzymes and genetic elements. Preparation of liposomes results in different
      properties for these systems. In addition, based on preparation methods,
      liposomes types can be unilamellar, multilamellar and giant unilamellar; however,
      there are many factors and difficulties that affect the development of liposome
      drug delivery structure. In the present review, we discuss some problems that
      impact drug delivery by liposomes. In addition, we discuss a new generation of
      liposomes, which is utilized for decreasing the limitation of the conventional
      liposomes.

PMID- 28507933
TI  - Novel Pentablock Copolymers as Thermosensitive Self-Assembling Micelles for
      Ocular Drug Delivery.
AB  - Many studies have focused on how drugs are formulated in the sol state at room
      temperature leading to the formation of in situ gel at eye temperature to provide
      a controlled drug release. Stimuli-responsive block copolymer hydrogels possess
      several advantages including uncomplicated drug formulation and ease of
      application, no organic solvent, protective environment for drugs, site
      specificity, prolonged and localized drug delivery, lower systemic toxicity, and
      capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling
      block copolymers (such as diblock, triblock, and pentablock copolymers) with
      large solubility variation between hydrophilic and hydrophobic segments are
      capable of making temperature-dependent micellar assembles, and with further
      increase in the temperature, of jellifying due to micellar aggregation. In
      general, molecular weight, hydrophobicity, and block arrangement have a
      significant effect on polymer crystallinity, micelle size, and in vitro drug
      release profile. The limitations of creature triblock copolymers as initial burst
      release can be largely avoided using micelles made of pentablock copolymers.
      Moreover, formulations based on pentablock copolymers can sustain drug release
      for a longer time. The present study aims to provide a concise overview of the
      initial and recent progresses in the design of hydrogel-based ocular drug
      delivery systems.

PMID- 28507935
TI  - Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents.
AB  - Phytoconstituents have been utilized as medicines for thousands of years, yet
      their application is limited owing to major hurdles like deficit lipid
      solubility, large molecular size and degradation in the gastric environment of
      gut. Recently, phospholipid-complex technique has unveiled in addressing these
      stumbling blocks either by enhancing the solubilizing capacity or its
      potentiating ability to pass through the biological membranes and it also
      protects the active herbal components from degradation. Hence, this phospholipid
      complex-technique can enable researchers to deliver the phytoconstituents into
      systemic circulation by using certain conventional dosage forms like tablets and
      capsules. This review highlights the unique property of phospholipids in drug
      delivery, their role as adjuvant in health benefits, and their application in the
      herbal medicine systems to improve the bioavailability of active herbal
      components. Also we summarize the prerequisites for phytosomes preparation like
      the selection of type of phytoconstituents, solvents used, various methods
      employed in phytosomal preparation and its characterization. Further we discuss
      the key findings of recent research work conducted on phospholipid-based delivery
      systems which can enable new directions and advancements to the development of
      herbal dosage forms.

PMID- 28507936
TI  - Thermal Stability and Kinetic Study of Fluvoxamine Stability in Binary Samples
      with Lactose.
AB  - Purpose: In the present study the incompatibility of FLM (fluvoxamine) with
      lactose in solid state mixtures was investigated. The compatibility was evaluated
      using different physicochemical methods such as differential scanning calorimetry
      (DSC), Fourier-transform infrared (FTIR) spectroscopy and mass spectrometry.
      Methods: Non-Isothermally stressed physical mixtures were used to calculate the
      solid-state kinetic parameters. Different thermal models such as Friedman, Flynn
      Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) were used for the
      characterization of the drug-excipient interaction. Results: Overall, the
      incompatibility of FLM with lactose as a reducing carbohydrate was successfully
      evaluated and the activation energy of this interaction was calculated.
      Conclusion: In this research the lactose and FLM Maillard interaction was proved
      using physicochemical techniques including DSC and FTIR. It was shown that DSC-
      based kinetic analysis provides fast and versatile kinetic comparison of
      Arrhenius activation energies for different pharmaceutical samples.

PMID- 28507934
TI  - The Challenges of Recombinant Endostatin in Clinical Application: Focus on the
      Different Expression Systems and Molecular Bioengineering.
AB  - Angiogenesis plays an essential role in rapid growing and metastasis of the
      tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy.
      Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical
      application challenges including; short half-life, instability in serum and
      requirement to high dosage. Therefore, production of recombinant endostatin (rEs)
      is necessary in large scale. The production of rEs is difficult because of its
      structural properties and is high-cost. Therefore, this review focused on the
      different expression systems that involved in rEs production including;
      mammalian, baculovirus, yeast, and Escherichia coli (E. coli) expression systems.
      The evaluating of the results of different expression systems declared that none
      of the mentioned systems can be considered to be generally superior to the other.
      Meanwhile with considering the advantages and disadvantage of E. coli expression
      system compared with other systems beside the molecular properties of Es, E. coli
      expression system can be a preferred expression system for expressing of the Es
      in large scale. Also, the molecular bioengineering and sustained release
      formulations that lead to improving of its stability and bioactivity will be
      discussed. Point mutation (P125A) of Es, addition of RGD moiety or an additional
      zinc biding site to N-terminal of Es , fusing of Es to anti-HER2 IgG or heavy
      chain of IgG, and finally loading of the endostar by PLGA and PEG- PLGA
      nanoparticles and gold nano-shell particles are the effective bioengineering
      methods to overcome to clinical changes of endostatin.

PMID- 28507937
TI  - The Utilization of RNA Silencing Technology to Mitigate the Voriconazole
      Resistance of Aspergillus Flavus; Lipofectamine-Based Delivery.
AB  - Purpose: Introducing the effect of RNAi in fungi to downregulate essential genes
      has made it a powerful tool to investigate gene function, with potential
      strategies for novel disease treatments. Thus, this study is an endeavor to delve
      into the silencing potentials of siRNA on cyp51A and MDR1 in voriconazole
      resistant Aspergillus flavus as the target genes. Methods: In this study, we
      designed three cyp51A-specific siRNAs and three MDR1-specific siRNAs and after
      the co-transfection of siRNA into Aspergillus flavus, using lipofectamine, we
      investigated the effect of different siRNA concentrations (5, 15, 25, 50nM) on
      cyp51A and MDR1 expressions by qRT-PCR. Finally, the Minimum Inhibitory
      Concentrations (MICs) of voriconazole for isolates were determined by broth
      dilution method. Results: Cyp51A siRNA induced 9, 22, 33, 40-fold reductions in
      cyp51A mRNA expres-sion in a voriconazole-resistant strain following the
      treatment of the cells with concentrations of 5, 15, 25, 50nM siRNA,
      respectively. Identically, the same procedure was applied to MDR1, even though it
      induced 2, 3, 4, 10-fold reductions. The results demonstrated a MIC for
      voriconazole in the untreated group (4ug per ml), when compared to the group
      treated with cyp51A-specific siRNA and MDR1-specific siRNA, both at
      concentrations of 25 and 50nM, yielding 2ug per ml and 1ug per ml when 25 nM was
      applied and 2ug per ml and 0.5ug per ml when the concentration doubled to 50 nM.
      Conclusion: In this study, we suggested that siRNA-mediated specific inhibition
      of cyp51A and MDR1 genes play roles in voriconazole-resistant A.flavus strain and
      these could be apt target genes for inactivation. The current study promises a
      bright prospect for the treatment of invasive aspergillosis through the effective
      deployment of RNAi and gene therapy.

PMID- 28507938
TI  - Vitamin D3-Loaded Nanostructured Lipid Carriers as a Potential Approach for
      Fortifying Food Beverages; in Vitro and in Vivo Evaluation.
AB  - Purpose: Nanostructured lipid carriers (NLCs) composed of solid lipid and oil are
      a new generation of lipid nanoparticles which have exhibited some merits over
      traditional used lipid nanoparticles in fortifying food and beverages and
      nutraceuticals delivery systems such as liposomes and solid lipid nanoparticles.
      Methods: In this study, Precirol and Compritol as solid lipids, Miglyol and
      Octyloctanoat as liquid lipids, Tween80, Tween20 and Poloxamer407 as surfactants
      were used to prepare vitamin D3-loaded NLC dispersion using hot homogenization
      method. The particle size and size distribution for all formulations were
      evaluated by immediately after production and during a storage period of 60 days.
      Results: The Precirol-based NLC showed superiority over Compritol-based NLC in
      the point of physical stability. Results clearly suggested that an optimum
      concentration of 3% of Poloxamer407 or 2% of Tween20 was sufficient to cover the
      surface of nanoparticles effectively and prevent agglomeration during the
      homogenization process. Octyloctanoat was introduced for the first time as a good
      substituent for Miglyol in the preparation of NLC formulations. The vitamin D3
      Intestinal absorption enhanced by the incorporating in NLCs. Conclusion: It was
      concluded that NLC showed a promising approach for fortifying beverages by
      lipophilic nutraceuticals such as vitamin D.

PMID- 28507939
TI  - Variables Associated with Adherence to Stress Ulcer Prophylaxis in Patients
      Admitted to the General Hospital Wards: A Prospective Study.
AB  - Purpose: The dramatic increase in stress ulcer prophylaxis (SUP) prescribing
      patterns over the past several years has raised concerns regarding to their
      appropriate utilization. This prospective study attempted to evaluate the trend
      of adherence to stress ulcer prophylaxis from admission until discharge in non-
      Intensive care unit (ICU) setting. Additionally, we attempted to find those
      variables associated with appropriate SUP administration. Methods: Data
      collection was performed prospectively to evaluate 195 randomly selected adult
      patients who received SUP or had indication for that in non-ICU wards of one of
      the largest referral center in Iran, during 6 months. Adherence was studied
      according to widely accepted American Society of Health system Pharmacists (ASHP)
      guideline. Univariate and multivariate logistic regression was also performed to
      detect associations related to misuse of SUP. Results: We recognized total
      inappropriate use of SUP upon admission, during hospital stay and at discharge
      were somewhat identical at different time points (61%, 80% and 77.4%
      respectively). On the other hand, since small number of patients experienced SUP
      underutilization, unfortunately this was not possible to elucidate factors that
      may have effect on this flawed behavior. However, increasing age was identified
      to be significant variable in SUP overutilization. Conclusion: This prospective
      study highlighted inappropriate overutilization of SUP within non-critically ill
      patients and found factors which predicted this behavior. Adherence during
      hospital stay was also calculated for the first time in this study, which was
      related to SUP adherence upon hospital admission.

PMID- 28507940
TI  - Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression.
AB  - Purpose: Mammalian target of rapamycin (mTOR)is important in hematopoiesis and
      affect cell growth,differentiation and survival. Although previous studies were
      identified the effect of cytokines on the mononuclear cells development however
      the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim
      of this study was to evaluate mTOR expression in cord blood mononuclear and cord
      blood stem cells (CD34+ cells) in culture conditions for lymphoid cell
      development. Methods: Isolation of The mononuclear cells (MNCs) from umbilical
      cord blood were done with use of Ficollpaque density gradient. We evaluated
      cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15
      at distinct time points during 21 days by using flow cytometry. In this study, we
      presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood
      cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15
      in day 14 and afterword reduced. However in persence of IL2 and IL15 expression
      of mTOR significantly reduced. mTOR expression in CD34+ cells decreased
      significantly from day7 to day 21 in culture. Conclusion: cytokines play
      important role in mTOR expression during hematopoiesis and development of cord
      blood mononuclear cells.

PMID- 28507941
TI  - In vitro Cytotoxicity Effects of 197Au/PAMAMG4 and 198Au/PAMAMG4 Nanocomposites
      Against MCF7 and 4T1 Breast Cancer Cell Lines.
AB  - Purpose: Study on gold based therapeutic agents for cancer cells deracination has
      become under scrutiny in recent years owing to effective treatments are not
      available for rapidly progressive cancers. The aim of present study was to
      examine efficiency of radioactive 198Au/PAMAMG4 and non-radioactive 197Au/PAMAMG4
      nancomposites against 4T1 and MCF7 breast cancer cell lines. Methods: The PAMAMG4
      dendrimer was treated with the gold anions and then, the mixture was chemically
      reduced by NaBH4. Prepared 197Au/PAMAMG4 was bombarded by thermal neutrons in the
      Tehran Research Reactor to 198Au/PAMAMG4 be produced. Prepared nanocomposites
      were characterized by means of FT-IR, 1H NMR, Zeta-potential measurements, TEM
      and EDX analyses. The radionuclidic purity of the 198Au/PAMAMG4 solution was
      determined using purity germanium (HPGe) spectroscopy and its stability in the
      presence of human serum was studied. In vitro studies were carried out to compare
      toxicity of PAMAMG4, 197Au/PAMAMG4 and 198Au/PAMAMG4 towards 4T1 and MCF7
      cancerous cells and C2C12 normal cell lines. Results: Characterization results
      exhibited that invitro agents, 197Au/PAMAMG4 and 198Au/PAMAMG4, were synthesized
      successfully. Cells viability after 24 h, 48 h, and 72 h incubation, using MTT
      assay showed that the toxicity of 198Au/PAMAMG4 is significantly superior in
      comparison with 197Au/PAMAMG4 and PAMAMG4. Furthermore, the toxicity of
      198Au/PAMAMG4 was higher on cancerous cells especially in higher level of
      concentrations after 72 hours (P<0.05). Conclusion: In the current study, the
      preparation of 197Au/PAMAMG4 and 198Au/PAMAMG4 is described and the cytotoxic
      properties of them against the MCF7, 4T1 cancerous cells and C2C12 normal cells
      were evaluated using MTT assay.

PMID- 28507942
TI  - Quality Properties of Sesame and Olive Oils Incorporated with Flaxseed Oil.
AB  - Purpose: Suitable ratio of essential fatty acids has an important role in
      maintaining good health. There is no pure oil with an ideal fatty acid
      composition and oxidative stability. The main goal of the present study was to
      evaluate the physical, chemical and nutritional properties of oil obtained by
      blending flaxseed oil as a rich source of omega3 fatty acids with sesame and
      olive oils. Methods: Three different ratios (65:30:5, 60:30:10 and 55:30:15) were
      prepared using olive, sesame and flaxseed oils. These mixtures were stored at 4
      degrees C and 24 degrees C and their quality and physicochemical properties were
      determined by measuring the fatty acid composition, phenolic compound, peroxide,
      anisidine values and schaal tests. Results: Fatty acid composition indicated that
      adding 10% and 15% flaxseed oil into blends have suitable ratio of essential
      fatty acids. The sample which contained 5% flaxseed oil had the highest phenolic
      content among treatments and these compounds showed a significant decrease during
      storage. A significant increase (p<0.05) was observed in peroxide values of all
      samples during storage. Increasing the flaxseed oil content in the blends, lead
      to an increase of the anisidine value. Conclusion: Blending sesame and olive oils
      with flaxseed oil produced oil blends with a good balance of essential fatty
      acids. Although peroxide and anisidine values increased during storage of the oil
      blends; the blends were of a good quality for home and industrial use.

PMID- 28507943
TI  - Effect of Solubilizers on the Androgenic Activity of Basella Alba L.
      (Basellaceae) in Adult Male Rats.
AB  - Purpose: Solubilizers play an important role in dissolution of pharmacological
      ingredients and should properly dissolve the active principle(s) while preserving
      its activities. This study investigated the effect of starch, gelatin,
      methylcellulose and polyvinylpyrrolidone 10000 in the preservation of the
      androgenic activity of the methanol extract Basella alba (MEBa). Methods:
      Different groups of male albino rats were orally given the MEBa (1 mg/kg)
      dissolved into either 1% gelatin (1% gel), %1 methylcellulose (1% MC) and 1%
      polyvinylpyrrolidone 10000 (1% PVP 10000) or 2% starch solution (2% SS) for 30
      days. Thereafter, animals were sacrificed and serum testosterone and creatinine
      levels as well as alanine aminotransferase (ALT) activity determined. Vital and
      reproductive organs were dissected out and weighed, while liver thiobarbituric
      acid reactive substances (TBARS) and glutathione levels were determined. Results:
      Different treatments did not affect the animal body and organ weights. The MEBa
      stimulatory effect on testosterone production was preserved with 2% SS and 1% PVP
      10000 as vehicles. Increased liver glutathione and TBARS levels were also
      observed in the animals fed with the MEBa dissolved in 2% SS and 1% Gel,
      respectively, while other biochemical parameters remained unchanged. Conclusion:
      Starch and polyvinylpyrrolidone 10000 stand as good preservation agents for MEBa
      androgenic activity, with starch exhibiting additional antioxidant activity
      through increase of glutathione levels.

PMID- 28507944
TI  - A Survey on Phytochemical Composition and Biological Activity of Zygophyllum
      fabago from Iran.
AB  - Purpose: Zygophyllum fabago L. (Z. fabago) is a widespread perennial herb which
      is used as a medicinal plant in traditional medicine of Iran, Turkey and China.
      The present study was a survey on phytochemical constituents and biological
      activities of this plant. Methods: Methanolic extract of the roots was
      fractionated over a C-18 pre-packed cartridge (Sep-pak) and chromatographic
      separation was performed on a reversed-phase preparative HPLC. Structural
      elucidation of the isolated compounds was carried out using UV, 1H-NMR and 13C
      NMR spectral analyses. Furthermore, the chemical compositions of the essential
      oil of the aerial parts were identified by GC-MS analysis. Antiproliferative and
      antioxidant activities of all extracts from aerials were determined by MTT and
      DPPH assays, respectively. Results: Phytochemical investigation on the plant
      roots led to the isolation and identification of two the 60% methanol-water Sep
      pak fraction, a prenylated flavone glycoside, 6-C-prenyl-7-O-[ beta -D-4'''-O
      acetyl-glucopyranosyl-(1'''->2'')-beta-D-glucopyranosyl] apigenin, which was
      named as a Zygocaperoside and also, other flavonoid, was named as the
      Isorhamnetin -3-O glucoside. None of the extracts showed antiproliferative effect
      against cancerous cells. However, among the extracts, methanolic extract
      indicated antioxidant activity. Moreover, essential oils of flowers and leaves of
      plant have high amounts of sesquiterpene hydrocarbons and diterpenoides.
      Conclusion: The results of present study introduce Z. fabago roots as a new
      source of flavonoid glycosides and suggest it as an appropriate candidate for
      further pharmacological studies.

PMID- 28507945
TI  - Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum)
      Against Staphylococci Infection. In Vivo Study in Rats.
AB  - Purpose: This study observed the effect of garlic extracts and amoxicillin
      against an induced staphylococcal infection model. MIC and MBC were also obtained
      for aqueous extracts of Allium sativum (Asa) and Allium tuberosum (Atu) against
      Staphylococcus aureus penicillin-sensitive (PSSA - ATCC 25923) and MRSA (ATCC
      33592). Methods: Granulation tissues were induced in the back of 205 rats. After
      14 days, 0.5 mL of 108 CFU/mL of PSSA or MRSA were injected inside tissues. After
      24h, animals were divided: G1 (Control) - 0.5 mL of NaCl 0.9%; G2 - Asa 100 mg/kg
      or 400mg/kg; G3 - Atu 100 mg/kg or 400 mg/kg; G4 - amoxicillin suspension 50
      mg/kg, considering PSSA infection; and G5 (Control) - 0.5 mL of NaCl 0.9%; G6 -
      Asa 400mg/kg; G7 - amoxicillin 50 mg/kg; and G8 - Asa 400 mg/kg + amoxicillin 50
      mg/kg for MRSA. All treatments were administered P.O. every 6h. Animals were
      killed at 0, 6, 12 and 24h. Samples were spread on salt-mannitol agar. Colonies
      were counted after 18 h at 37  degrees C. Atu was not able to inhibit or kill
      PSSA and MRSA. Considering Asa, MIC and MBC against PSSA were 2 mg/mL and 4
      mg/mL, respectively; and 16 mg/mL and 64 mg/mL against MRSA. Results: No effect
      was observed in vivo for control, Asa 100 mg/kg and Atu 100 mg/kg, while
      amoxicillin, Atu 400 mg/kg and Asa 400 mg/kg decreased PSSA counts in all-time
      points. No effect of any group against MRSA was observed at any time. Conclusion:
      Thus, A. sativum and A. tuberosum were able to reduce PSSA infection, but not
      MRSA infection.

PMID- 28507946
TI  - Conditioned Medium of Wharton's Jelly Derived Stem Cells Can Enhance the
      Cartilage Specific Genes Expression by Chondrocytes in Monolayer and Mass Culture
      Systems.
AB  - Purpose: Mesenchymal stem cells (MSCs) have been introduced for cell therapy
      strategies in osteoarthritis (OA). Despite of their capacity for differentiation
      into chondrocyte, there are some evidences about their life-threatening problem
      after transplantation. So, some researchers shifted on the application of stem
      cells conditioned medium. The goal of this study is to evaluate whether Wharton's
      jelly derived stem cell conditioned medium (WJSCs-CM) can enhance the gene
      expression profile by chondrocytes in monolayer and mass culture systems.
      Methods: Conditioned medium was obtained from WJSCs at fourth passage. Isolated
      chondrocytes were plated at density of 1*106 for both monolayer and high density
      culture. Then cells in both groups were divided into control (received medium)
      and experiment group treated with WJ-CM for 3 and 6 days. Samples were prepared
      to evaluate gene expression profile of collagen II, aggrecan, cartilage
      oligomeric matrix protein (COMP) and sox-9 using real-time RT-PCR. Results: After
      3 days, Chondrocytes treated with WJSCs-CM expressed significantly higher level
      of genes compared to the control group in both culture systems. After 6 days, the
      expression of genes in monolayer cultivated chondrocytes was decreased but that
      of the mass culture were up-regulated significantly. Conclusion: WJ-SCs-CM can
      increase the expression of cartilage-specific genes and can be introduced as a
      promoting factor for cartilage regeneration.

PMID- 28507947
TI  - Preparation, Optimization and Activity Evaluation of PLGA/Streptokinase
      Nanoparticles Using Electrospray.
AB  - Purpose: PLGA nanoparticles (NPs) have been extensively investigated as carriers
      of different drug molecules to enhance their therapeutic effects or preserve them
      from the aqueous environment. Streptokinase (SK) is an important medicine for
      thrombotic diseases. Methods: In this study, we used electrospray to encapsulate
      SK in PLGA NPs and evaluate its activity. This is the first paper which
      investigates activity of an electrosprayed enzyme. Effect of three input
      parameters, namely, voltage, internal diameter of needle (nozzle) and
      concentration ratio of polymer to protein on size and size distribution (SD) of
      NPs was evaluated using artificial neural networks (ANNs). Optimizing the SD has
      been rarely reported so far in electrospray. Results: From the results, to obtain
      lowest size of nanoparticles, ratio of polymer/enzyme and needle internal
      diameter (ID) should be low. Also, minimum SD was obtainable at high values of
      voltage. The optimum preparation had mean (SD) size, encapsulation efficiency and
      loading capacity of 37 (12) nm, 90% and 8.2%, respectively. Nearly, 20% of SK was
      released in the first 30 minutes, followed by cumulative release of 41% during 72
      h. Activity of the enzyme was also checked 30 min after preparation and 19.2%
      activity was shown. Conclusion: Our study showed that electrospraying could be an
      interesting approach to encapsulate proteins/enzymes in polymeric nanoparticles.
      However, further works are required to assure maintaining the activity of the
      enzyme/protein after electrospray.

PMID- 28507949
TI  - Voltammetric Determination of Ivabradine Hydrochloride Using Multiwalled Carbon
      Nanotubes Modified Electrode in Presence of Sodium Dodecyl Sulfate.
AB  - Purpose: A new sensitive sensor was fabricated for the determination of
      ivabradine hydrochloride (IH) based on modification with multiwalled carbon
      nanotubes using sodium dodecyl sulfate as micellar medium to increase the
      sensitivity. Methods: The electrochemical behavior of IH was studied in Britton
      Robinson buffer (pH: 2.0-11.0) using cyclic and differential pulse voltammetry.
      Results: The voltammetric response was linear over the range of 3.984 x 10-6
      3.475 x 10-5 mol L-1. The limits of detection and quantification were found to be
      5.160 x 10-7 and 1.720 x 10-6 mol L-1, respectively. Conclusion: This method is
      suitable for determination of IH in tablets and plasma.

PMID- 28507950
TI  - Preparation and Characterization of Pistacia khinjuk Gum Nanoparticles Using
      Response Surface Method: Evaluation of Its Anti-Bacterial Performance and
      Cytotoxicity.
AB  - Purpose: This study aims to prepare a novel, natural nanoparticle (NP) as a drug
      carrier, which also has inherent therapeutic effects. Methods: Pistacia khinjuk
      gum NPs were prepared and Response surface methodology (RSM) was used for
      statistical analysis of data and optimizing the size of NPs. Results: NPs were in
      the range of 75.85-241.3 nm. The optimization study was carried out, and an
      optimized size (70.86nm) was obtained using DMSO as a solvent. The volume of the
      organic phase was 111.25ul, and the concentration of gum was 1% w/v. The cell
      viability assay was performed on the pure gum and NPs toward beta-TC3, MCF7, and
      HT29 cell lines. It was observed that NPs have higher cytotoxic activity in
      comparison with pure gum, and that the IC50value was achieved at 1% of NPs in
      beta-TC3 cells. The obtained NPs demonstrated antibacterial activity against two
      bacterial strains (Pseudomonas aeruginosa and Staphylococcus aureus). Conclusion:
      Altogether, according to the obtained results, these NPs with inherent
      cytotoxicity and antibacterial activity are an attractive carrier for drug
      delivery.

PMID- 28507948
TI  - Characterizing the Hot Spots Involved in RON-MSPbeta Complex Formation Using In
      Silico Alanine Scanning Mutagenesis and Molecular Dynamics Simulation.
AB  - Purpose: Implication of protein-protein interactions (PPIs) in development of
      many diseases such as cancer makes them attractive for therapeutic intervention
      and rational drug design. RON (Recepteur d'Origine Nantais) tyrosine kinase
      receptor has gained considerable attention as promising target in cancer therapy.
      The activation of RON via its ligand, macrophage stimulation protein (MSP) is the
      most common mechanism of activation for this receptor. The aim of the current
      study was to perform in silico alanine scanning mutagenesis and to calculate
      binding energy for prediction of hot spots in protein-protein interface between
      RON and MSPbeta chain (MSPbeta). Methods: In this work the residues at the
      interface of RON-MSPbeta complex were mutated to alanine and then molecular
      dynamics simulation was used to calculate binding free energy. Results: The
      results revealed that Gln193, Arg220, Glu287, Pro288, Glu289, and His424 residues
      from RON and Arg521, His528, Ser565, Glu658, and Arg683 from MSPbeta may play
      important roles in protein-protein interaction between RON and MSP. Conclusion:
      Identification of these RON hot spots is important in designing anti-RON drugs
      when the aim is to disrupt RON-MSP interaction. In the same way, the acquired
      information regarding the critical amino acids of MSPbeta can be used in the
      process of rational drug design for developing MSP antagonizing agents, the
      development of novel MSP mimicking peptides where inhibition of RON activation is
      required, and the design of experimental site directed mutagenesis studies.

PMID- 28507951
TI  - The Phytochemical Bergenin Enhances T Helper 1 Responses and Anti-Mycobacterial
      Immunity by Activating the MAP Kinase Pathway in Macrophages.
AB  - Tuberculosis (TB) remains one of the greatest health concerns worldwide, which
      has hindered socioeconomic development in certain parts of the world for many
      centuries. Although current TB therapy, "Directly Observed Treatment Short
      course," is effective, it is associated with unwanted side effects and the risk
      for the generation of drug-resistant organisms. The majority of infected
      individuals successfully confine the mycobacterial organisms and remain
      asymptotic unless immune responses are perturbed. Thus, host immunity can protect
      against TB and immunomodulation is therefore an attractive therapeutic option.
      Previous studies have shown that TNF-alpha and Nitric Oxide (NO) in conjunction
      with IFN-gamma-producing T helper 1 (Th1) cells play critical roles in host
      protection against TB. Here, we show that bergenin, a phytochemical isolated from
      tender leaves of Shorea robusta, activates the MAP kinase and ERK pathways and
      induces TNF-alpha, NO and IL-12 production in infected macrophages. We further
      show that bergenin induces Th1 immune responses and potently inhibits bacillary
      growth in a murine model of Mycobacterium tuberculosis infection. These findings
      identify bergenin as a potential adjunct to TB therapy.

PMID- 28507952
TI  - Comparison of Growth and the Cytokines Induced by Pathogenic Yersinia
      enterocolitica Bio-Serotypes 3/O: 3 and 2/O: 9.
AB  - Pathogenic Yersinia enterocolitica is widely distributed in China where the
      primary bio-serotypes are 3/O: 3 and 2/O: 9. Recently, the distribution of 2/O: 9
      strains are being gradually replaced by 3/O: 3 strains where presently 3/O: 3
      strains are the major pathogenic Y. enterocolitica in China. To identify the
      growth conditions and cytokines induced by Y. enterocolitica and providing some
      clues for this shift, we performed competitive growth in vitro and in vivo for
      these two bio-serotype strains; and we also compared the cytokines induced by
      them in infected BALB/C mice. We found 2/O: 9 strains grew more in vitro, while
      3/O: 3 strains grew more in vivo regardless of using single cultures or mixed
      cultures. The cytokines induced by the two strains were similar: interleukin-6
      (IL-6), IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), chemokines
      (KC), monocyte chemotactic protein 1 (MCP-1), macrophage inflammation protein
      1alpha (MIP-1alpha), tumor necrosis factor-alpha (TNF-alpha), and RANTES were
      statistically up-regulated upon activation of normal T cells compared to the
      control. The cytokine values were higher in mixed infections than in single
      infections except for IL-6, G-CSF, and KC. The data illustrated the different
      growth of pathogenic Y. enterocolitica bio-serotype 3/O: 3 and 2/O: 9 in vitro
      and in vivo, and the cytokine changes induced by the two strains in infected
      BALB/C mice. The growth comparisons of two strains maybe reflect the higher
      pathogenic ability or resistance to host immune response for Y. enterocolitica
      bio-serotype 3/O: 3 and maybe it as one of the reason for bacteria shift.

PMID- 28507955
TI  - Patient is centre of all Medical Research.

PMID- 28507953
TI  - Influence of Microbes on Neutrophil Life and Death.
AB  - Neutrophils are the most abundant leukocyte in humans and they are among the
      first white cells recruited to infected tissues. These leukocytes are essential
      for the innate immune response to bacteria and fungi. Inasmuch as neutrophils
      produce or contain potent microbicides that can be toxic to the host, neutrophil
      turnover and homeostasis is a highly regulated process that prevents unintended
      host tissue damage. Indeed, constitutive neutrophil apoptosis and subsequent
      removal of these cells by mononuclear phagocytes is a primary means by which
      neutrophil homeostasis is maintained in healthy individuals. Processes that alter
      normal neutrophil turnover and removal of effete cells can lead to host tissue
      damage and disease. The interaction of neutrophils with microbes and molecules
      produced by microbes often alters neutrophil turnover. The ability of microbes to
      alter the fate of neutrophils is highly varied, can be microbe-specific, and
      ranges from prolonging the neutrophil lifespan to causing rapid neutrophil lysis
      after phagocytosis. Here we provide a brief overview of these processes and their
      associated impact on innate host defense.

PMID- 28507956
TI  - An Unusual Case of Giant Cell Tumor of First Metatarsal: A Rare Case Report and
      Review of Literature.
AB  - INTRODUCTION: Giant cell tumor (GCT) or osteoclastoma is an osteolytic, mostly
      benign but locally aggressive tumor occurring in young adults at the epiphysis.
      Area of predilection is mainly long bones (85-90%). 4% of GCT are also found in
      iliac bone, spine and only 2% in hand (of which GCT phalanges are more common
      than metacarpal). GCT of metatarsal is a very rare occurrence with very few cases
      being reported so far. We report a case of GCT 1st metatarsal in a 40-year-old
      male which is a very rare entity. We shall discuss the clinical features,
      pathological and radiological hallmarks, and the various treatment modalities of
      such lesion. CASE REPORT: A 40-year-old male presented with complain of swelling
      over the dorsum of left foot for the duration of 2 years and pain in that foot
      for 4 months. Swelling was insidious in onset and has progressively increased in
      size. Pain was mild to moderate in intensity, dull aching and continuous. On
      examination, there was a localized ovoid shaped swelling 7 by 4 cm over the
      dorsum of the left foot opposing 1st and 2nd metatarsal area with well-defined
      margins, tender on deep palpation, hard in consistency and the overlying skin was
      free. Radiographs revealed an expansile osteolytic lesion of entire 1st
      metatarsal involving the articular surface of tarsometatarsal joint and
      metatarsophalangeal joint with impingement on 1st metatarsal and cortical
      thinning. The classical "soap bubble appearance" was also present. Fine needle
      aspiration cytology was done to confirm our diagnosis of GCT. According to
      Campanacci et al., the tumor was histologically graded as Grade II tumor. A
      reconstructive surgery with fusion of the Cuneiform metatarsa and
      metatarsophalangeal joint was planned. The tumor was carefully removed with a
      cuff of normal tissue and the proximal and distal joints were inspected. There
      was no articular cartilage of the Cuneiform metatarsa joint. A fibular graft was
      taken and was inserted into the troughs created in medial cuineform and proximal
      phalanx and fixed with K-wire, both proximally and distally. The patient was
      given a below knee cast for three months postoperatively. Full weight bearing was
      started after 3 months. After 9 months of follow-up, the graft was well taken up
      and there were no signs of recurrence both clinically and radiologically.
      CONCLUSION: Local resection of the involved metatarsal with autograft or
      allograft replacement is the preferred surgical treatment for several reasons.
      First, no correlation has been found between the grade of GCT and the rate of
      recurrence. Therefore, all giant tumors of foot should be considered locally
      aggressive. In addition curettage with or without bone grafts has resulted in
      recurrence rates of about 90%. Thus curettage is an unacceptable form of
      treatment. Second, although amputation may prevent recurrence, it is cosmetically
      deforming and decreases the function of the foot.

PMID- 28507954
TI  - With Friends Like These: The Complex Role of Neutrophils in the Progression of
      Severe Pneumonia.
AB  - Pneumonia is a leading cause of death from infection in the United States and
      across the globe. During pulmonary infection, clear resolution of host
      inflammatory responses occurs in the absence of appreciable lung damage.
      Neutrophils are the first wave of leukocytes to arrive in the lung upon
      infection. After activation, neutrophils traffic from the vasculature via
      transendothelial migration through the lung interstitium and into the alveolar
      space. Successful pulmonary immunity requires neutrophil-mediated killing of
      invading pathogens by phagocytosis and release of a myriad of antimicrobial
      molecules, followed by resolution of inflammation, neutrophil apoptosis, and
      clearing of dead or dying neutrophils by macrophages. In addition to their
      antimicrobial role, it is becoming clear that neutrophils are also important
      modulators of innate and adaptive immune responses, primarily through the release
      of cytokines and recruitment of additional waves of neutrophils into the airways.
      Though typically essential to combating severe pneumonia, neutrophil influx into
      the airways is a double-edged sword: Overzealous neutrophil activation can cause
      severe tissue damage as a result of the release of toxic agents including
      proteases, cationic polypeptides, cytokines, and reactive oxygen species (ROS)
      aimed at killing invading microbes. In extreme cases, the damage caused by
      neutrophils and other innate immune mediators become the primary source of
      morbidity and mortality. Here, we review the complex role of neutrophils during
      severe pneumonia by highlighting specific molecules and processes that contribute
      to pulmonary immunity, but can also drive progression of severe disease.
      Depending on the identity of the infectious agent, enhancing or suppressing
      neutrophil-mediated responses may be key to effectively treating severe and
      typically lethal pneumonia.

PMID- 28507958
TI  - Bifocal Cryptococcal Osteomyelitis in an Immunocompetent Male.
AB  - INTRODUCTION: Cryptococcus neoformans commonly affects lungs and central nervous
      system that to in immunocompromised individual. Bony involvement is extremely
      rare and most common site is vertebrae and usual presentation is monofocal. CASE
      REPORT: We present 18-year-old male with bifocal osteomyelitis of scapula and
      tibia in immunocompetent male. CONCLUSION: Cryptococcal osteomyelitis should be
      kept as a differential diagnosis in a patient as a primary diagnosis to avoid
      diagnostic delay and morbidity associated with it.

PMID- 28507957
TI  - Arthroscopic Synovectomy in Bilateral Lipoma Arborescens.
AB  - INTRODUCTION: Lipoma arborescens (LA) is an uncommon condition that consists of a
      villous lipomatous proliferation of the synovial membrane. Open synovectomy has
      been previously selected as a curative treatment option. In recent years, some
      authors have published good results with arthroscopic interventions. We describe
      a well-documented case of bilateral LA of the knees treated with staged
      arthroscopic synovectomy. CASE REPORT: A 48-year-old North American woman without
      a history of trauma presented with recurrent effusions and mild pain in both knee
      joints for many years. Magnetic resonance imaging examinations confirmed the
      diagnosis of bilateral LA with multiple villous lipomatous synovial
      proliferations pattern. Degenerative changes of the medial meniscus were detected
      bilaterally. The patient underwent bilateral arthroscopic anterior synovectomy
      and partial medial meniscectomy of the knee with three portal techniques.
      Arthroscopic the knee joint contained a large number or finger-shaped synovial
      proliferations with yellowish good vascularized diffuse villous masses in the
      suprapatellar bursa and intercondylar fossa. The cartilage showed degenerative
      changes with Outerbridge Grade II to III, which was particularly severe in the
      femoropatellar compartment. Histopathological examination of the villous masses
      demonstrated papillary hypertrophy, slight hyperplasia, vascular hyperplasia with
      a slight degree of stromal fibrosis, and interstitial lymphoplasmacytic
      inflammation. The adipose cells were reduced in number in relation to a normal
      finding but had a normal aspect without any pathological changes. 25 months after
      the first operation, the patient reported pain relief with the preserved
      function. Magnetic resonance examination of both knee joints at the last follow
      up showed no relapse of the disease. The Knee injury and Osteoarthritis Outcome
      Score improved on the right knee joint from 39.3 preoperatively to 85.1 at the
      last follow-up, and on the left knee joint from 54.2 preoperatively to 86.3 at
      the last follow-up. CONCLUSION: Arthroscopic anterior synovectomy is an efficient
      method of achieving good results in LA with multiple villous lipomatous synovial
      proliferations pattern.

PMID- 28507959
TI  - Intramuscular Arteriovenous Hemangioma of Thigh: A Case Report and Review of
      Literature.
AB  - INTRODUCTION: Skeletal muscle hemangiomas are uncommon soft tissue tumors; more
      than 90% are misdiagnosed initially. They present as chronic pain and swelling in
      a muscle with or without a history of trauma. Magnetic resonance imaging is the
      investigation of choice. Many treatment modalities for the symptomatic
      hemangiomas are available of which surgical excision is the most preferred. CASE
      REPORT: We present an unusual case of pain, swelling, and restriction of
      movements in the right knee following an episode of trauma in an 8-year-old boy
      diagnosed to have intramuscular arteriovenous hemangioma in the vastusmedialis
      and vastusintermedius for which he was treated by surgical excision and followed
      for 2 years and found to have no recurrence. CONCLUSION: Skeletal muscle
      hemangiomas are completely treatable; the knowledge of their natural history,
      clinical findings, and imaging appearances are of great importance for proper
      diagnosis and treatment.

PMID- 28507960
TI  - A Case Report of Sleeve Fracture of the Patella in a Shield.
AB  - INTRODUCTION: Sleeve fractures of the patella are rare fractures that only occur
      in children. The diagnosis is difficult both clinically and radiologically since
      the distal bony fragment may be too small to be detectable by radiography. A high
      riding patella and hemarthrosis are important signs of sleeve fractures. CASE
      REPORT: A 12-year-old boy was admitted to the emergency room after having felt a
      severe pain in his left knee on kicking the ground while skateboarding earlier
      that day. Knee swelling, tense hemarthrosis, and periarticular tenderness were
      noted. On physical examination, an extension lag of 15 was observed. The active
      range of motion of the injured knee was 45-90 degrees  of flexion. Radiography
      showed an avulsion fracture of the lower pole of the patella and a high-riding
      patella. At the next day after the injury, we performed open reduction and
      internal fixation surgery. Open reduction with transosseous tunneling and
      cerclage wiring was performed because the distal bony fragment was too small for
      tension band wiring to be used. At 9 months after surgery, there was no extension
      lag, and the active range of motion of the injured knee was 0-140 degrees  of
      flexion. Callus formation over the fracture site and bone union was confirmed,
      and the cerclage wire was removed. To date, he had no further symptoms and has
      been able to carry out all types of physical activities, including skateboarding.
      CONCLUSION: Although sleeve fractures in children are uncommon, it should be
      considered a possibility in children with a chief complaint of pain around the
      knee. Open reduction and internal fixation was effective in the treatment of
      sleeve fracture of the patella.

PMID- 28507961
TI  - Total Hip Arthroplasty Indicated for a Tuberculous Coxitis Complicating a
      Controlled Acquired Imunodefficiency Syndrom Condition: A Preliminary Report
      Concerning a Case.
AB  - INTRODUCTION: Total hip arthroplasty (THA) remains controversial in active
      tuberculosis (TB) infection because of the risks of septic loosening and
      reactivation of the infection. We present a rare case of THA in a patient
      positive for the human immunodeficiency virus (HIV) with active tuberculous
      coxitis. The aim of this work is to share our experience and our preliminary
      results. CASE REPORT: The patient was a 53-year-old Black African woman, positive
      for the HIV, who was operated for implantation of a THA via the Hardinge approach
      indicated for a severe painful hip with restriction of joint movement and limp. A
      creamy-white liquid was noticed in the hip joint which was negative for urgent
      Gram-staining. The surgery was completed with the implantation of a hybrid THA.
      The post-operative period was uneventful, and she was put on antituberculous
      drugs following a positive histology result for TB, and to continue her
      antiretroviral drugs. She still has a satisfactory result for 3 years since her
      surgery. CONCLUSION: On condition that the patient is put simultaneously on
      triple antibiotics and antituberculous drugs, we propose that THA could be an
      option in patient presenting with the association of HIV infection and active
      tuberculous coxitis.

PMID- 28507962
TI  - Dislocation Intermediate Cuneiform with Fracture Medial Cuneiform.
AB  - INTRODUCTION: Dislocation of intermediate cuneiform is a rare injury in English
      language literature. Dislocation of intermediate cuneiform with undisplaced
      medial cuneiform fracture has been reported only once. We report the first case
      of dislocation intermediate cuneiform with displaced medial cuneiform fracture.
      CASE REPORT: A 43-year-old male was diagnosed of dislocation of intermediate
      cuneiform with fracture medial cuneiform after a road traffic accident. This was
      treated by a method of distractor application that is only reported in navicular
      fracture dislocation. This treatment method avoids open reduction with minimal of
      complications and good outcome. CONCLUSION: Distractor technique was applied for
      the first time in cuneiform fracture dislocation in this case, and we recommend
      it to avoid open reduction. The previous reported injuries in this region were
      mostly treated by open reduction. Due to the rarity of this injury and technique,
      our case adds to the literature a novel reduction method.

PMID- 28507963
TI  - Evaluation of Efficacy of Three-dimensional Stainless Steel Mini-Plates in the
      Treatment of Fractures of the Mandible: A Prospective Study.
AB  - INTRODUCTION: The purpose of the study was to analyze whether adequate fracture
      fixation can be achieved by three-dimensional (3D) stainless steel mini-plates
      its ease of placement, whether the patient can resume function early and to find
      out the need to do intermaxillary fixation. MATERIALS AND METHODS: In the
      prospective study, we treated 12 patients and 17 fractured sites using 3D mini
      plates. Once fracture reduction was achieved temporary intermaxillary fixation
      (IMF) was done occlusion was achieved and the fractured segments were fixed using
      3D plates either 4-holed or 6-holed of 2.5 mm thickness and 6-8 mm length screws.
      IMF was removed subsequently. CONCLUSION: In none of the cases non-union or
      malocclusion was noted. Similarly except for 2 cases which had associated
      subcondylar fractures IMF was not done postoperatively. The patients were able to
      achieve function immediately with a reasonable level of success. The interincisal
      opening ranged from 18 to 23 mm in the first week to 40-56 mm after 1 month.

PMID- 28507964
TI  - Intra-articular Migration of Broken Patellar Tension Band Wire: A Rare Case.
AB  - INTRODUCTION: Comminuted fracture of patella is most commonly treated by tension
      band wiring with cerclage wiring. Broken cerclage wiring after such surgery is
      not uncommon but intra-articular migration of broken cerclage wire is rarely
      known and described complication. CASE REPORT: A 51-year-old male patient of
      Indian origin which was treated, 15 months back for fracture patella with tension
      band wiring with cerclage wiring, presented with painful restriction of knee
      movements for the last 4 weeks. X-ray showed cerclage wire had broken at multiple
      sites with one broken piece migrated intra-articular. This case is unique due to
      the size of migrated broken cerclage wire which was about 4.5 cm long, second the
      anterior part of broken wire was hooked around anterior cruciate ligament, which
      prevented its further migration otherwise neurovascular structures could have
      been damaged. This intra-articular piece of wire was removed arthroscopically.
      CONCLUSIONS: We recommend that all patients receiving bone fixation with wires
      should be counseled about the risks of hardware failure and possible migration,
      with the option of elective hardware removal discussed. In addition, when wire
      breakage is detected radiologically, the patient should be strongly advised to
      have the wires removed as soon as possible.

PMID- 28507965
TI  - Posterior Hip Dislocation with Ipsilateral Femoral Head and Shaft Fracture -
      Using a Temporary External Fixator as a Method for Closed Reduction.
AB  - INTRODUCTION: Complex fractures are increasing because of various traumatic
      mechanisms. They drift from standard classifications, and their treatment is
      controversial. Of such cases are hip dislocations with associated fractures of
      the ipsilateral femur. CASE REPORT: This case report describes the condition of a
      30-year-old man involved in a motor vehicle collision. Clinical examination, X
      rays, and computed tomography scan revealed a posterior hip dislocation with an
      ipsilateral femoral head and mid-shaft fractures. The patient was treated by
      closed reduction of hip dislocation using a temporarily applied external fixator
      followed by intramedullary nailing of the femoral shaft. Achieving a closed
      reduction is a challenge with ipsilateral fractures but it should be favored over
      open reduction due to a lower risk of complications. The type of femoral head
      fracture, in this case, may have aided in an easier reduction. CONCLUSION: Hip
      dislocation is an orthopedic emergency and its treatment is challenging if
      associated with ipsilateral fractures. The decision of a closed versus an open
      approach should be made after considering the management plans of other injuries.

PMID- 28507966
TI  - Ipsilateral Hip and Knee Dislocation with Open Tibial Fracture: A Case Report of
      a Limb Threatening Injury.
AB  - INTRODUCTION: Hip or knee dislocations are usually treated as a surgical
      emergency, but ipsilateral hip and knee dislocation should be considered a dual
      emergency that must be addressed immediately and reduced at the earliest. We
      present here the sequence of events and the final functional outcome of one such
      rare injury manages by us. CASE REPORT: A 22-year-old male was involved in a road
      traffic accident. He presented to the emergency department in 4 h injury time
      with painful deformities of the right hip and knee, along with Type I open wound
      right leg with abnormal mobility suggestive of fracture in the ipsilateral leg.
      CONCLUSION: Simultaneous ipsilateral hip and knee fracture-dislocation with open
      tibial fracture is a rare injury that should be approached as limb-threatening
      injury and dual orthopedic emergency. We report this case for its rarity and to
      document that good results can be achieved with early appropriate treatment.

PMID- 28507967
TI  - Surgery of a Rare Case of Multiple Synovial Osteochondromatosis of the Hip Joint.
AB  - INTRODUCTION: Primary synovial osteochondromatosis of the hip is a benign
      disorder, which is not frequently seen clinically. The characteristic of this
      disease is proliferation of synovium and formation of loose bodies inside the
      joint. It is known that only the loose bodies derived from synovium were called
      synovial osteochondromatosis. Although it can take place in any joint, the knee
      is most commonly affected, involvement of the hip joint is relatively rare. We
      report a young man who has multiple synovial osteochondromatosis in his left hip.
      CASE REPORT: A 21-year-old young man, who had progressive pain and functional
      impairment of his left hip, came to our hospital. He complained that 2 years ago,
      he began to feel painful of his left hip joint when walking and squatting.
      Physical examination found that the motion range of the hip was obviously
      limited, with internal rotation, abduction in particular. The Harris hip score
      was just 38 points. X-ray shew multiple osteochondromatosis with mild
      degenerative osteoarthritis existing inside the hip joint. Magnetic resonance
      imaging shew that the synovial osteochondromatosis intersperse inside the hip
      joint. During the operation, posterolateral incision of the hip was chosen with
      dislocation of the femoral head for total exposure of the hip joint to debride
      extensive loose bodies and proliferative synovial tissue. Pulse irrigation was
      applied to flush out the residuals. More than 872 of osteochondromatosis were
      removed out of the hip joint (some small ones were sucked during the operation).
      The size of the loose bodies ranged from 3 cm * 3 cm * 2.5 cm to 0.2 cm * 0.2 cm
      * 0.15 cm. Post-operation radiography shew most pathological tissues were taken
      out. After the operation, the patient rehabilitated fast. The pain relieved and
      he could bear weight and walked 3 days postoperatively. 1 and 3 months
      postoperatively, the patient came to us for visit, and he said that he just had a
      relatively satisfactory function of his affected hip. He could walk, slowly run,
      and squat freely. But sometimes he could feel a bit painful on his left hip joint
      after long walking and fatigue. And sometimes he could feel and hear mild
      crepitus on the left hip joint. 12 months later, the patient came again and
      complained that the pain of his operated hip became a bit more serious than
      before since about 20 days ago. The range (internal rotation, abduction in
      particular) of this hip joint could not live up to normal, compared with the
      uninvolved hip in physical examination. X-ray shew osteoarthritis had become a
      bit severer. The patient accepted the suggestion of prospective total hip
      replacement. CONCLUSION: Multiple synovial osteochondromatosis is not a very
      uncommon condition. However, there may be unusual presentations. It can take
      place in any joint, the knee is most commonly affected, however, involvement of
      the hip joint is relatively rare as was seen in our patient.

PMID- 28507968
TI  - Posttraumatic Static Volar Intercalated Segment Instability - Iatrogenic or
      Missed Injury.
AB  - INTRODUCTION: Carpal instability is broad category consisting of various patterns
      of injury, with dissociative type more common. CASE REPORT: A 13 -year -old boy
      presented at 6 months following a fall with restriction of wrist movements.
      Patient had sustained a closed distal one -third both bones fracture forearm
      fixed with K -wire, and volar lunate instability was found during sequential
      follow -up. CONCLUSION: Posttraumatic carpal instability should be identified at
      the earliest to avoid poor hand function and morbidity associated with it.

PMID- 28507969
TI  - Core Decompression with Synthetic Grafting as a Joint Preservation Strategy in
      Humeral Avascular Necrosis Due to Sickle Cell Anemia: A Case Report.
AB  - INTRODUCTION: Avascular necrosis (AVN) of the femoral or humeral heads in
      patients with sickle cell anemia is a common and painful condition. There is
      currently no gold standard treatment protocol for this condition. Typically, the
      pain is managed with narcotics and activity restriction until there has been
      collapse of the subchondral bone with a degree of arthrosis sufficient to warrant
      total joint arthroplasty. This method entails prolonged pain for the patient and
      decreases the ability to function occupationally and recreationally. CASE REPORT:
      A 51-year-old African-American woman with a history of sickle cell anemia
      presented for the evaluation of significant bilateral shoulder pain that was
      confirmed to be AVN via radiographs and magnetic resonance imaging of both her
      humeral heads without joint collapse. She tried and failed conservative
      management with physical therapy and optimization of sickle cell treatment with
      pain medications for years, so she desired surgical management. Arthroscopically
      assisted core decompression of her humeral heads with synthetic grafting was
      performed in an attempt at joint preservation. CONCLUSION: This report
      demonstrates a technique of staged decompression of necrotic bone in the
      bilateral humeral heads with synthetic bone grafting to determine if this could
      function as a joint preservation strategy. This procedure was considered
      successful to alleviate the patients' pain in both of her arms. The application
      of this procedure is significant because it could be used in various future
      medical joint preservation cases for a wide range of patients.

PMID- 28507970
TI  - A New Technique for Surgical Treatment of Proximal Hamstring Tendinopathy in a
      Triathlon Athlete.
AB  - INTRODUCTION: Proximal hamstring tendinopathy (PHT) is the result of chronic
      overload caused by repetitive eccentric contraction. Surgical treatment becomes
      an option for patients with chronic symptoms that do not respond to conservative
      treatment. CASE REPORT: This report describes a case of a 48-year-old man, an
      amateur triathlete, with deep gluteal pain in the left hip for 12 months, leading
      to a decline in sports performance. Magnetic resonance imaging revealed
      abnormalities that suggested a PHT. Surgery was indicated following the failure
      of conservative treatments. Debridement of the conjoint tendon and its
      reinsertion associated with semimembranosus tenotomy showed good results and is
      thus an option for the treatment of this pathology after 12 months of follow-up.
      CONCLUSION: This article provides surgeons with a new surgical option for this
      debilitating condition with clinical and functional improvement after 12 months
      of follow-up.

PMID- 28507971
TI  - Lethal Necrotizing Fasciitis Triggered by Plaster: Case Report and Review of
      Literature.
AB  - INTRODUCTION: Plasters have been frequently associated with known complications
      such as infection, and compartment syndrome or deep vein thrombosis. However,
      life-threatening complication of necrotizing fasciitis (NF) has not been
      frequently attributed to plaster. CASE REPORT: We had a case of a 62-year male
      developing a lethal NF triggered by a below knee plaster for undisplaced fracture
      medial malleolus after twisting injury. He had no history suggestive of diabetes,
      renal impairment, and predisposing allergic factors or any comorbidity. Despite
      early diagnosis and aggressive management with above knee amputation, death
      occurs due to septic shock on the 20th day. A similar case of reported lethal NF
      triggered by plaster has also been reviewed in this report. CONCLUSION: This case
      highlights a life-threatening rare complication of plaster and author recommends
      thorough clinical history taking, precleaning of limb, use of sterile water and
      use of adequate wrap around skin for gypsum plasters as prevention apart from
      high index of suspicion for early diagnosis, and rapid management.

PMID- 28507972
TI  - Bilateral Coracoid Avulsion Fractures with Unilateral Anterior Instability with
      Glenoid Bone Loss: Use of Avulsed Fragment for Reconstruction of Glenoid.
AB  - INTRODUCTION: Coracoid fractures are often missed since the fracture is not
      visualized in a routine anteroposterior view of the shoulder and special views
      are not ordered. Shoulder dislocation is common but it is rare to have a
      dislocation with a coracoid fracture. The purpose of this paper is to present the
      rare occurrence of bilateral coracoid fractures in a patient with unilateral
      anterior shoulder instability managed using the same fractured coracoid fragment
      by the latarjet procedure. CASE REPORT: We report a case of 48 -year -old male
      who presented to us with a history of recurrent dislocations of the left
      shoulder. He had frequent episodes of tonic-clonic seizures 5 years back. He was
      diagnosed to be suffering from neurocysticercosis of the brain for which he was
      successfully treated. He did not have any episode of seizure later, but he
      continued to have repeated episodes of dislocation on his left side only. On
      examination of his left shoulder, he had normal range of motion. He was found to
      be very apprehensive, even in the midrange. This made us to suspect glenoid bone
      loss and hence both magnetic resonance imaging and three -dimensional computed
      tomography (CT) scan of the left shoulder were ordered. The CT scan revealed
      bilateral coracoid fractures along with glenoid bone loss. An open bony procedure
      including iliac crest bone graft was planned after a diagnostic arthroscopy
      keeping in mind that the latarjet procedure may not be possible due to the
      coracoid fracture. During the operation, we found that the coracoid fragment was
      large enough to perform a latarjet procedure rather than doing an iliac crest
      bone graft. This itself provided stability of the shoulder on abduction and
      external rotation by providing a bony block not requiring any further procedure
      for the Hill -Sachs lesion. CONCLUSION: Epileptic patients should undergo CT scan
      evaluation for glenoid bone loss, large Hill -Sachs lesion and to rule out
      coracoid fractures to plan for bony stabilization procedure and since we have
      used the same fractured coracoids fragment for latarjet procedure and found to be
      successful, this add on the knowledge to the orthopedic community.

PMID- 28507973
TI  - Intratendinous Ganglion Cyst of the Semitendinosus Tendon: First Reported Case
      and Literature Review.
AB  - INTRODUCTION: Ganglion cysts are commonly seen in wrist joints and knee joint,
      but intra-tendinous ganglion cysts are extremely rare. We report the first case
      of intratendinous ganglion cyst of semi-tendinous tendon. CASE REPORT: A 4-year
      old boy presented with painless soft tissue swelling over knee with no history of
      recent trauma. Radiograph was normal and USG showed a well-defined hypoechoic
      cystic lesion. Patient was taken for surgery and the lesion was removed. Lesion
      came out to be a ganglion cyst originating from the semitendinosus tendon. Post
      operative USG was done to confirm complete removal of the ganglion. CONCLUSION:
      Intra-articular ganglion cysts are common, and we find it regularly in our daily
      practice. However, we should be aware of the occurrence of intratendinous
      ganglion cysts also which on examination may look like a lipoma. Thus for all
      cysts around the tendons, an USG is must. Also repeat USG should be done to rule
      out incomplete excision and recurrence.

PMID- 28507974
TI  - A Rare Presentation of Cervical Spine Osteochondroma.
AB  - INTRODUCTION: Cervical spine osteochondromas are rare tumors that usually involve
      the posterior spinal elements. Osteochondromas of the cervical spine presenting
      anteriorly as a mass over the supraclavicular region has not been reported in the
      literature. CASE REPORT: A 12-year-old boy presented with right sided
      supraclavicular swelling. Plain radiographs revealed a bony mass. Computerized
      tomography (CT) and magnetic resonance imaging scans of the cervical region
      showed a bony mass arising from pedicle and encroaching onto lamina of C6
      vertebra. He underwent excision biopsy of the mass through an anterior approach.
      The histopathological diagnosis was osteochondroma. At 4-year follow-up, he was
      asymptomatic and CT scan revealed no recurrence. CONCLUSION: Tumors arising from
      the posterior elements are difficult to diagnose by plain radiographs alone and
      require special imaging modalities to show their exact location, nature, and
      extent.

PMID- 28507975
TI  - Charcot Fracture in the Calcaneus after Total Knee Arthroplasty: A Case Report.
AB  - INTRODUCTION: Only a few reports have described calcaneus fractures after total
      knee arthroplasty (TKA). Therefore, in this report, we describe a case of
      calcaneal avulsion fracture that occurred 5 weeks after a TKA in a relatively
      young male patient with syphilis. CASE REPORT: A 63-year-old man with syphilis
      had Charcot joint of the right knee. The patient developed severe varus deformity
      and contracture and experienced severe pain in the knee. TKA was performed to
      alleviate the pain and improve the patient's gait. The patient noticed slight
      heel pain 4 weeks after the TKA, and a calcaneus avulsion fracture in the
      ipsilateral foot was diagnosed without any trauma 1 week later. Open reduction
      internal fixation was performed with cannulated cancellous screws and a cerclage
      wire. 3 weeks after the surgery, partial weight bearing was permitted in an
      orthotic device. Full weight-bearing was allowed at 7 weeks after surgery. The
      surgical wounds healed without complications. The calcaneus fracture successfully
      achieved bone union with appropriate surgical intervention and aftercare.
      CONCLUSION: The previous studies have shown that calcaneus stress fracture may
      occur in elderly osteoporotic women after TKA. Patients with peripheral
      neuropathy may develop a Charcot fracture after minimal trauma because of
      decreased protective sensation, even if the patient is a relatively young man
      without osteoporosis. Charcot joint disease is also considered to be a risk
      factor for calcaneal stress fracture and Charcot fracture after TKA.

PMID- 28507976
TI  - Painful Pseudowinging and Snapping of Scapula due to Subscapular Osteochondroma:
      A Case Report.
AB  - INTRODUCTION: Osteochondroma or exostosis is most common benign bone tumors. They
      are usually seen in the metaphyses of long bones with more than 35% of cases
      affecting the bone around the knee and are seldom found in flat bones like
      scapula. When present in scapula, they may cause abnormal scapulothoracic
      movements leading to pain, snapping, and pseudowinging of scapula. CASE REPORT:
      We describe a novel case of osteochondroma arising on the ventral aspect of right
      scapula in a 16-year-old otherwise healthy female patient causing snapping and
      pseudowinging of scapula and occasional pain in affected area. X-ray and computed
      tomography findings were consistent with an abnormal bony mass arising on ventral
      aspect of superior border of the scapula. The patient was treated with open
      extraperiosteal resection of the mass with relief of symptoms. The
      histopathological diagnosis was consistent with osteochondroma with no signs of
      malignancy. CONCLUSION: In a patient with winging and snapping of scapula one
      should be aware of rare diagnosis osteochondroma along with other more common
      etiology.

PMID- 28507977
TI  - A Sub-acute Septic Arthritis of the Knee; a Sequelae to Thorn Prick Injury of
      Patella: A Case Report.
AB  - INTRODUCTION: Sub-acute septic arthritis of knee following a thorn prick injury
      to patella is an uncommon condition and seen in active playful children. The
      child may be afraid to narrate the incident to their parents or examining doctor,
      so a high index of suspicion is must. The delayed presentation is inevitable.
      Early synovitis due to the organic biological foreign body may progress to septic
      arthritis, if untreated may result in knee stiffness or chronic osteomyelitis of
      patella. CASE REPORT: We report a case of thorn prick injury to the left patella
      in an 8-years-old boy who neglected the incident of thorn prick while playing
      with his peer group 10 days ago and presented with features of sub-acute septic
      arthritis. He was treated by arthrotomy, double inspection of the patella,
      removal of foreign body, synovectomy, lavage, antibiotics, and aggressive
      rehabilitation with an excellent outcome. CONCLUSION: Sub-acute synovitis in
      active playful children should raise the suspicion of thorn prick even though no
      proper history is explained. Organic foreign body from plant materials is
      radiolucent and easily missed. High suspicion and timely surgical intervention,
      double inspection during arthrotomy identifies the foreign body. Once removed,
      with proper antibiotic and physiotherapy protocol followed has an excellent
      outcome.

PMID- 28507978
TI  - Modified Tension - Slide Technique for Anatomical Distal Biceps Tenodesis using a
      Bicortical EndoButton and a Tenodesis Screw.
AB  - INTRODUCTION: Many surgical techniques have been described in the literature. In
      this article, we describe surgical technical details along with tips and tricks
      of distal biceps tendon tenodesis using the EndoButton and tension - slide
      technique, a modification of the suspensory cortical button technique, which
      allows the surgeon to tension and repairs the biceps tendon through the single
      longitudinal anterior incision. This modification in surgical technique of using
      dual implants, i.e., EndoButton and interference screw as fixation tools and
      concept of tendon sliding principle made this procedure unique. In this article,
      we describe surgical technique along with tips and tricks of distal biceps tendon
      tenodesis using the EndoButton and tension - slide technique and also discussed
      about modification of EndoButton technique reported in many other articles to
      overcome the possible complications. CASE REPORT: We report six consecutive
      patients, presented with distal biceps tendon rupture (4 acute; 2 chronic cases)
      between June 2013 and March 2015, who underwent single-incision, anatomical
      distal biceps tenodesis procedure with bicortical EndoButton and tenodesis screw
      using tension slide technique. Radiographs were taken immediate post-operative to
      document for displacement or loosening of EndoButton if any. CONCLUSION: The use
      of an EndoButton and an interference screw for repairing distal biceps tendons
      have been previously described. We describe a modification of originally
      described technique which is worth considering, as it provides two levels of
      fixation, whilst avoiding possible complications of such procedures. It is ideal
      for repairing both acute and chronic ruptures, without the need for allograft or
      autograft augmentation and describes detailed technical steps to avoid possible
      iatrogenic complications.

PMID- 28507979
TI  - Microtubule-associated protein tau is associated with the resistance to docetaxel
      in prostate cancer cell lines.
AB  - Tau, a microtubule-associated protein, has been investigated primarily in
      neurons. Recently, tau has been explored to be associated with increased drug
      resistance in various kinds of cancers. We found that the tau was expressed in
      prostate cancer cell lines DU145 and PC-3. We also reported that recurrent
      prostate cancer cells after docetaxel treatment have higher levels of microtubule
      associated protein tau. In vitro, inactivation of tau by gene knockdown
      suppressed cell proliferation and sensitized docetaxel cytotoxicity. Also, our
      results demonstrated that the PI3K/Akt/mTOR pathway was upregulated in DU145
      docetaxel-resistant cells compared with the DU145-naive cells. Thus, targeting
      tau protein and PI3K/Akt/mTOR pathway are promising strategies to enhance
      docetaxel response for the treatment of prostate cancer.

PMID- 28507980
TI  - Hypertension in the Pediatric Kidney Transplant Recipient.
AB  - Hypertension after kidney transplant is a frequent occurrence in pediatric
      patients. It is a risk factor for graft loss and contributes to the significant
      burden of cardiovascular disease (CVD) in this population. The etiology of
      posttransplant hypertension is multifactorial including donor factors, recipient
      factors, medications, and lifestyle factors similar to those prevalent in the
      general population. Ambulatory blood pressure monitoring has emerged as the most
      reliable method for measuring hypertension in pediatric transplant recipients,
      and many consider it to be essential in the care of these patients. Recent
      technological advances including measurement of carotid intima-media thickness,
      pulse wave velocity, and myocardial strain using specked echocardiography and
      cardiac magnetic resonance imaging have improved our ability to assess CVD
      burden. Since hypertension remains underrecognized and inadequately treated, an
      early diagnosis and an appropriate control should be the focus of therapy to help
      improve patient and graft survival.

PMID- 28507981
TI  - A Quasi-Experimental Study of a Movement and Preliteracy Program for 3- and 4
      Year-Old Children.
AB  - OBJECTIVE: Approximately 28% of children are not ready for kindergarten, 91% are
      inactive according to current guidelines, and 21% are overweight/obese. Early
      intervention to strengthen movement and preliteracy skills may help to curb the
      concerning rates of poor school readiness, inactivity, obesity, and subsequently
      positively impact health across the lifespan. The objective of this pilot study
      was to evaluate the effectiveness of a motor and preliteracy skill program for a
      community sample of 3- to 4-year-old children. METHODS: A quasi-experimental
      study design was used. The program was run for 1 h/week for 10 weeks and
      consisted of movement skill instruction, free play, and an interactive reading
      circle with care-giver involvement throughout each session. Movement and
      preliteracy skills were assessed in all children pre- and post-intervention using
      the Peabody Developmental Motor Scales-2nd edition, the Preschool Word and Print
      Awareness tool, and the Phonological Awareness Literacy Screening tool. RESULTS:
      Nineteen families (experimental group, n = 8; control group, n = 11) were
      recruited (mean age = 3 years, 8 m; 47% male). There was a significant effect of
      group on gross motor raw scores overall [F(1, 16) = 4.67, p < 0.05; [Formula: see
      text]] and print-concept knowledge [F(1, 16) = 11.9, p < 0.05; [Formula: see
      text]]. CONCLUSION: This study was one of the first to examine the impact of a
      community-based movement skill and preliteracy program with care-giver
      involvement in preschool children. Future research should continue to explore the
      effects of the program with larger and more diverse samples on multiple health
      and developmental outcomes. CLINICAL TRIAL REGISTRATION: Play and Preliteracy
      among Young Children (PLAY) NCT02432443.

PMID- 28507982
TI  - The Role of Carrageenan and Carboxymethylcellulose in the Development of
      Intestinal Inflammation.
AB  - Although the exact pathophysiology remains unknown, the development of
      inflammatory bowel disease (IBD) is influenced by the interplay between genetics,
      the immune system, and environmental factors such as diet. The commonly used food
      additives, carrageenan and carboxymethylcellulose (CMC), are used to develop
      intestinal inflammation in animal models. These food additives are excluded from
      current dietary approaches to induce disease remission in Crohn's disease such as
      exclusive enteral nutrition (EEN) using a polymeric formula. By reviewing the
      existing scientific literature, this review aims to discuss the role that
      carrageenan and CMC may play in the development of IBD. Animal studies
      consistently report that carrageenan and CMC induce histopathological features
      that are typical of IBD while altering the microbiome, disrupting the intestinal
      epithelial barrier, inhibiting proteins that provide protection against
      microorganisms, and stimulating the elaboration of pro-inflammatory cytokines.
      Similar trials directly assessing the influence of carrageenan and CMC in humans
      are of course unethical to conduct, but recent studies of human epithelial cells
      and the human microbiome support the findings from animal studies. Carrageenan
      and CMC may trigger or magnify an inflammatory response in the human intestine
      but are unlikely to be identified as the sole environmental factor involved in
      the development of IBD or in disease recurrence after treatment. However, the
      widespread use of carrageenan and CMC in foods consumed by the pediatric
      population in a "Western" diet is on the rise alongside a corresponding increase
      in IBD incidence, and questions are being raised about the safety of frequent
      usage of these food additives. Therefore, further research is warranted to
      elucidate the role of carrageenan and CMC in intestinal inflammation, which may
      help identify novel nutritional strategies that hinder the development of the
      disease or prevent disease relapse post-EEN treatment.

PMID- 28507983
TI  - Epinephrine Use during Newborn Resuscitation.
AB  - Epinephrine use in the delivery room for resuscitation of the newborn is
      associated with significant morbidity and mortality. Evidence for optimal dose,
      timing, and route of administration of epinephrine during neonatal resuscitation
      comes largely from extrapolated adult or animal literature. In this review, we
      provide the current recommendations for use of epinephrine during neonatal
      resuscitation and also the evidence behind these recommendations. In addition, we
      review the current proposed mechanism of action of epinephrine during neonatal
      resuscitation, review its adverse effects, and identify gaps in knowledge
      requiring urgent research.

PMID- 28507985
TI  - Control of Neuronal Migration and Aggregation by Reelin Signaling in the
      Developing Cerebral Cortex.
AB  - The mammalian cerebral neocortex has a well-organized laminar structure, achieved
      by the highly coordinated control of neuronal migration. During cortical
      development, excitatory neurons born near the lateral ventricle migrate radially
      to reach their final positions to form the cortical plate. During this process,
      dynamic changes are observed in the morphologies and migration modes, including
      multipolar migration, locomotion, and terminal translocation, of the newborn
      neurons. Disruption of these migration processes can result in neuronal disorders
      such as lissencephaly and periventricular heterotopia. The extracellular protein,
      Reelin, mainly secreted by the Cajal-Retzius neurons in the marginal zone during
      development, plays a crucial role in the neuronal migration and neocortical
      lamination. Reelin signaling, which exerts essential roles in the formation of
      the layered neocortex, is triggered by the binding of Reelin to its receptors,
      ApoER2 and VLDLR, followed by phosphorylation of the Dab1 adaptor protein.
      Accumulating evidence suggests that Reelin signaling controls multiple steps of
      neuronal migration, including the transition from multipolar to bipolar neurons,
      terminal translocation, and termination of migration beneath the marginal zone.
      In addition, it has been shown that ectopically expressed Reelin can cause
      neuronal aggregation via an N-cadherin-mediated manner. This review attempts to
      summarize our knowledge of the roles played by Reelin in neuronal migration and
      the underlying mechanisms.

PMID- 28507984
TI  - Immunoprevalence to Six Waterborne Pathogens in Beachgoers at Boqueron Beach,
      Puerto Rico: Application of a Microsphere-Based Salivary Antibody Multiplex
      Immunoassay.
AB  - Waterborne infectious diseases are a major public health concern worldwide. Few
      methods have been established that are capable of measuring human exposure to
      multiple waterborne pathogens simultaneously using non-invasive samples such as
      saliva. Most current methods measure exposure to only one pathogen at a time,
      require large volumes of individual samples collected using invasive procedures,
      and are very labor intensive. In this article, we applied a multiplex bead-based
      immunoassay capable of measuring IgG antibody responses to six waterborne
      pathogens simultaneously in human saliva to estimate immunoprevalence in
      beachgoers at Boqueron Beach, Puerto Rico. Further, we present approaches for
      determining cutoff points to assess immunoprevalence to the pathogens in the
      assay. For the six pathogens studied, our results show that IgG antibodies
      against antigens from noroviruses GI.I and GII.4 were more prevalent (60 and
      51.6%, respectively) than Helicobacter pylori (21.4%), hepatitis A virus (20.2%),
      Campylobacter jejuni (8.7%), and Toxoplasma gondii (8%) in the saliva of the
      study participants. The salivary antibody multiplex immunoassay can be used to
      examine immunoprevalence of specific pathogens in human populations.

PMID- 28507989
TI  - Diagnostic Laparoscopy as Decision Tool for Re-recurrent Inguinal Hernia
      Treatment Following Open Anterior and Laparo-Endoscopic Posterior Repair.
AB  - INTRODUCTION: The guidelines of the international hernia societies recommend
      posterior repair in laparo-endoscopic technique for recurrent inguinal hernia
      after open anterior mesh repair and, conversely, open anterior repair for
      recurrence after laparo-endoscopic primary repair. Even when these guidelines are
      followed, already 1 year after repair a re-recurrence rate of 1-2% must be
      expected, with that rate rising further in the subsequent years. Accordingly,
      increasingly more patients with re-recurrence after anterior and posterior mesh
      implantation must be treated, which constitutes a problem that to date has been
      investigated in only very few studies. Hence, there are no well-founded
      recommendations. This paper now presents a number of case reports aimed at
      identifying the role of explorative laparoscopy as decision tool for re-recurrent
      inguinal hernia treatment. PATIENTS AND METHODS: Based on three case reports the
      role of explorative laparoscopy as decision tool for re-recurrent inguinal hernia
      treatment is presented below. RESULTS: In all the three cases described
      explorative laparoscopy played a key role as decision tool when deciding how best
      to treat re-recurrence after anterior and posterior inguinal hernia repair. In
      one case severe adhesions after robotic prostatectomy and in another case correct
      placement of the mesh in the posterior plane, adhesions from the cecum to the
      groin region and no definitive finding of a re-recurrence resulted in an open
      repair. In the third case, an insufficient laparoscopic posterior mesh placement
      made the re-recurrent TAPP procedure relatively easy. CONCLUSION: Explorative
      laparoscopy is an important decision tool for re-recurrent inguinal hernia
      treatment to minimize the risks of the procedure for the patients.

PMID- 28507987
TI  - Pitx2 in Embryonic and Adult Myogenesis.
AB  - Skeletal muscle is a heterogeneous tissue that represents between 30 and 38% of
      the human body mass and has important functions in the organism, such as
      maintaining posture, locomotor impulse, or pulmonary ventilation. The genesis of
      skeletal muscle during embryonic development is a process controlled by an
      elaborate regulatory network combining the interplay of extrinsic and intrinsic
      regulatory mechanisms that transform myogenic precursor cells into functional
      muscle fibers through a finely tuned differentiation program. However, the
      capacity of generating muscle still remains once these fibers have matured. Adult
      myogenesis resembles many of the embryonic morphogenetic episodes and depends on
      the activation of satellite cells that have the potential to differentiate into
      new muscle fibers. Pitx2 is a member of the bicoid family of homeodomain
      transcription factors that play an important role in morphogenesis. In the last
      decade, Pitx2 has emerged as a key element involved in the fine-tuning mechanism
      that regulates skeletal-muscle development as well as the differentiation and
      cell fate of satellite cells in adult muscle. Here we present an integrative view
      of all aspects of embryonic and adult myogenesis in which Pitx2 is involved, from
      embryonic development to satellite-cell proliferation, fate specification, and
      differentiation. Those new Pitx2 functions on satellite-cell biology might open
      new perspectives to develop therapeutic strategies for muscular disorders.

PMID- 28507988
TI  - Comparative Therapeutic Efficacy of 153Sm-EDTMP and 177Lu-EDTMP for Bone Pain
      Palliation in Patients with Skeletal Metastases: Patients' Pain Score Analysis
      and Personalized Dosimetry.
AB  - INTRODUCTION: The aim of the present study was to compare the therapeutic
      efficacy of 153Sm-EDTMP and 177Lu-EDTMP in pain palliation in cancer patients
      with skeletal metastases. MATERIALS AND METHODS: Thirty patients (25 M:5 F, mean
      age: 66.0 +/- 14.7 years) of breast/prostate cancer with documented skeletal
      metastases were recruited prospectively. Twenty patients were considered randomly
      for treatment with 153Sm-EDTMP and with 177Lu-EDTMP in 10 patients, respectively.
      Using fixed dose of 37.0 MBq/kg body weight of each, the mean administered doses
      of 153Sm-EDTMP and 177Lu-EDTMP were 2,155.2 +/- 419.6 MBq (1,347-2,857) and
      1,935.1 +/- 559.4 MBq (1,073-2,627), respectively. Anterior and posterior whole
      body images were acquired at different time points following radioactivity
      administration. The first data set of pre-void images (acquired at 0.5 h)
      representing the total activity of either of 153Sm-EDTMP or 177Lu-EDTMP was
      considered as reference images. All the serial images were used for patients'
      dosimetry analysis by using organ level internal dosimetry assessment algorithm.
      Reduction in pain scoring was assessed clinically over 8 weeks by using
      appropriate WHO criteria and correlated with the absorbed dose to the metastatic
      sites. RESULTS: A total of 86 metastatic lesions clearly visualized on post
      therapy serial images (matching on bone scans) were evaluated for absorbed dose
      calculations. Both 153Sm-EDTMP and 177Lu-EDTMP delivered similar absorbed dose to
      the metastatic sites, i.e., 6.22 +/- 4.21 and 6.92 +/- 3.92 mSv/MBq,
      respectively. The mean absorbed doses to various other organs were found to be
      comparable and within the safe limits. A complete response (CR) for each
      radionuclide was evaluated as 80.0%. No significant alternation in blood
      parameters and no untoward reaction were observed. However, a mild to severe
      toxicity was observed in two patients (1 each with 153Sm-EDTMP and 177Lu-EDTMP).
      Kaplan-Meier survival analysis demonstrated that 27/30 patients had pain-free
      survival (CR) up to the observational period of 8 weeks. However, no
      statistically significant correlation could be established between the pain
      scoring and absorbed dose to metastatic sites. CONCLUSION: Both the radionuclides
      thus offer an effective and comparable therapeutic efficacy for bone pain
      palliation at an affordable cost and can be used interchangeably as per the
      availability.

PMID- 28507986
TI  - More than Just a Simple Cardiac Envelope; Cellular Contributions of the
      Epicardium.
AB  - The adult pumping heart is formed by distinct tissue layers. From inside to
      outside, the heart is composed by an internal endothelial layer, dubbed the
      endocardium, a thick myocardial component which supports the pumping capacity of
      the heart and exteriorly covered by a thin mesothelial layer named the
      epicardium. Cardiac insults such as coronary artery obstruction lead to ischemia
      and thus to an irreversible damage of the myocardial layer, provoking in many
      cases heart failure and death. Thus, searching for new pathways to regenerate the
      myocardium is an urgent biomedical need. Interestingly, the capacity of heart
      regeneration is present in other species, ranging from fishes to neonatal
      mammals. In this context, several lines of evidences demonstrated a key
      regulatory role for the epicardial layer. In this manuscript, we provide a state
      of-the-art review on the developmental process leading to the formation of the
      epicardium, the distinct pathways controlling epicardial precursor cell
      specification and determination and current evidences on the regenerative
      potential of the epicardium to heal the injured heart.

PMID- 28507992
TI  - Current Concepts and Advancements in Management of Traumatic Brain Injury; A
      Glimpse at the Recently Published Evidence.

PMID- 28507990
TI  - Development of an Online, Evidence-Based Patient Information Portal for
      Congenital Heart Disease: A Pilot Study.
AB  - OBJECTIVES: In response to an increased need for patient information on
      congenital heart disease in the Netherlands, we initiated a nationwide initiative
      to develop an online, evidence-based patient information portal, starting with a
      pilot project aimed at the subgroup of patients with congenital aortic and
      pulmonary valve disease. METHODS AND RESULTS: We developed an information portal
      that aims to (1) improve patient knowledge and involvement and to subsequently
      reduce anxiety and decisional conflict and improve mental quality of life and (2)
      to support physicians in informing and communicating with their patients. The
      information portal was developed according to the systematic International
      Patient Decision Aid Standards development process employing Delphi techniques by
      a multidisciplinary workgroup of pediatric and adult congenital cardiologists, a
      congenital cardiothoracic surgeon, a psychologist, an epidemiologist, a patient
      representative, and web and industrial design experts. First, patients and
      physicians were surveyed and interviewed to assess the current state of patient
      information and explore their preferences and needs to determine the focus for
      the development of the information portal. We found that patient knowledge and
      numeracy are limited, reliable information is scarce, physicians inform patients
      selectively and patient involvement is suboptimal, and there is a need for more
      reliable, tailored, and multi-faceted information. Based on the findings of these
      surveys and interviews, a patient-tailored information portal was designed that
      presents evidence-based disease- and age-specific medical and psychosocial
      information about diagnosis, treatment, prognosis, and impact on daily life in a
      manner that is comprehensible and digestible for patients and that meets the
      needs expressed by both patients and physicians. The effect of the website on
      patient outcome is currently being assessed in a multicenter stepped-wedge
      implementation trial. CONCLUSION: The present pilot project succeeded in
      developing an online, evidence-based information portal that is supported by both
      patients and physicians. The information portal will be further developed and
      expanded to include all other major forms of congenital heart disease,
      translations into other languages, and a public information portal to serve
      patients' relatives and the general public at large.

PMID- 28507991
TI  - Evaluation of Bioequivalence of Two Long-Acting 20% Oxytetracycline Formulations
      in Pigs.
AB  - The aim of this study was to explore the bioequivalence of long-acting
      oxytetracycline in two formulations, a reference formulation (Terramycin 20% LA,
      Pfizer) and a test one (Kangtekang 20% LA, Huishen). Both formulations were
      administered intramuscularly at 20 mg/kg body weight at each of 24 healthy
      animals during a two-period crossover parallel experimental design. The
      oxytetracycline (OTC) concentrations in plasma were measured by high-performance
      liquid chromatography, and the limit of quantification was 0.05 ug/ml with a
      recovery ratio of above 90%. Moreover, the descriptive pharmacokinetics
      parameters (Cmax, AUC0-144h, and AUC0-infinity) were calculated and compared
      under analysis of variance, and 90% confidence interval (CI) were compared,
      except for Tmax analyzed by non-parametric tests based on Wilcoxons's signed rank
      test. The comparison results of Cmax, AUC0-144h, AUC0-infinity, and Tmax were
      5.066 +/- 0.486, 5.071 +/- 0.877 ug/ml, 118.926 +/- 13.259, 126.179 +/- 17.390 ug
      h/ml, 123.087 +/- 13.906, 130.732 +/- 18.562 ug h/ml, 0.740 +/- 0.278, 0.650 +/-
      0.258 h, respectively, and did not reveal any significant differences. In
      addition, 90% CIs of these ratios for reference and test product were within an
      interval of 80-125%, and the relative bioavailability of test one was (94.291 +/-
      15.287)%. Therefore, it has been concluded that test OTC was bioequivalent to the
      reference formulation in pigs.

PMID- 28507994
TI  - A Step-by-Step Framework on Discrete Events Simulation in Emergency Department; A
      Systematic Review.
AB  - OBJECTIVE: To systematically review the current literature of simulation in
      healthcare including the structured steps in the emergency healthcare sector by
      proposing a framework for simulation in the emergency department. METHODS: For
      the purpose of collecting the data, PubMed and ACM databases were used between
      the years 2003 and 2013. The inclusion criteria were to select English-written
      articles available in full text with the closest objectives from among a total of
      54 articles retrieved from the databases. Subsequently, 11 articles were selected
      for further analysis. RESULTS: The studies focused on the reduction of waiting
      time and patient stay, optimization of resources allocation, creation of crisis
      and maximum demand scenarios, identification of overcrowding bottlenecks,
      investigation of the impact of other systems on the existing system, and
      improvement of the system operations and functions. Subsequently, 10 simulation
      steps were derived from the relevant studies after an expert's evaluation.
      CONCLUSION: The 10-steps approach proposed on the basis of the selected studies
      provides simulation and planning specialists with a structured method for both
      analyzing problems and choosing best-case scenarios. Moreover, following this
      framework systematically enables the development of design processes as well as
      software implementation of simulation problems.

PMID- 28507993
TI  - Enhanced Recovery after Emergency Surgery: A Systematic Review.
AB  - OBJECTIVE: To evaluate the current scientific evidence for the applicability,
      safety and effectiveness of pathways of enhanced recovery after emergency surgery
      (ERAS). METHODS: We undertook a search using PubMed and Cochrane databases for
      ERAS protocols in emergency cases. The search generated 65 titles; after
      eliminating the papers not meeting search criteria, we selected 4 cohort studies
      and 1 randomized clinical trial (RCT). Data extracted for analysis consisted of:
      patient age, type of surgery performed, ERAS elements implemented, surgical
      outcomes in terms of postoperative complications, mortality, length of stay (LOS)
      and readmission rate. RESULTS: The number of ERAS items applied was good, ranging
      from 11 to 18 of the 20 recommended by the ERAS Society. The implementation
      resulted in fewer postoperative complications. LOS for ES patients was shorter
      when compared to conventional care. Mortality, specifically reported in three
      studies, was equal or lower with ERAS. Readmission rates varied widely and were
      generally higher for the intervention group but without statistical significance.
      CONCLUSIONS: The studies reviewed agreed that ERAS in emergency surgery (ES) was
      feasible and safe with generally better outcomes. Lower compliance with some of
      the ERAS items shows the need for the protocol to be adapted to ES patients. More
      evidence is clearly required as to what can improve outcomes and how this can be
      formulated into an effective care pathway for the heterogeneous ES patient.

PMID- 28507995
TI  - The Necessity of Data Mining in Clinical Emergency Medicine; A Narrative Review
      of the Current Literatrue.

PMID- 28507996
TI  - Effects of Pulsed Electromagnetic Field with Predatory Stress on Functional and
      Histological Index of Injured-Sciatic Nerve in Rat.
AB  - OBJECTIVE: To assess the effect of combination of pulsed electromagnetic fields
      (PEMF) with predatory stress on transected sciatic nerve regeneration in rats.
      METHODS: In sham- operated group (SOG) the nerve was manipulated and left intact.
      The 10-mm rat sciatic nerve gap was created in rats. In transected group
      (Transected) nerve stumps were sutured to adjacent muscle and in vein graft group
      (VG) the gap was bridged using an inside-out vein graft. In VG/PEMF group the
      transected nerve was bridged using vein graft, phosphate buffered saline was
      administered into the graft and the whole body was exposed to PEMF. In VG/PS
      group the transected nerve was bridged using vein graft, phosphate buffered
      saline was administered into the graft and the rats underwent predatory stress
      (PS).  In VG/PEMF/PS group the transected nerve was bridged using vein graft,
      phosphate buffered saline was administered into the graft, the whole body was
      exposed to PEMF and the rats underwent predatory stress. The regenerated nerve
      fibers were studied within 12 weeks after surgery. RESULTS: Functional,
      gastrocnemius muscle mass findings and morphometric indices confirmed faster
      recovery of regenerated axons in VG/PEMF and VG/PEMF/PS groups compared to those
      in the other groups (p=0.001). The whole body exposure to PEMF improved
      functional recovery. Predatory stress did not affect nerve regeneration in the
      animals undergone predatory stress (p=0.343). CONCLUSION: Pulsed electromagnetic
      fields could be considered as an effective, safe and tolerable treatment for
      peripheral nerve repair in clinical practice.

PMID- 28507997
TI  - Recognizing Sudden Cardiac Arrest May Require More Than Two Questions during
      Telephone Triage: Developing a Complementary Checklist.
AB  - OBJECTIVE: To develop decision-support tools to identify patients experiencing
      sudden cardiac arrest (SCA). METHODS: Eighty calls related to SCA were content
      analyzed, and the contextual patterns that emerged were organized into a
      checklist. Two researchers independently analyzed the recorded calls and compared
      their findings. Eighteen dispatchers scored 20 cases (which included SCA and non
      SCA cases) both with and without the checklist. Correct responses for each case
      and agreement among dispatchers have been reported. RESULTS: Eighty audio files
      (total time, 96 min) were analyzed, and a total of 602 codes were extracted from
      the text and recordings. The caller's tone of voice and presence or absence of
      background voices, calling for an ambulance and giving the dispatcher the address
      promptly, and description of the primary complaint and respirations accounted for
      38%, 39%, and 23% of all codes, respectively. A 15-item complementary checklist
      has been developed. The mean percentages of correct responses were 66.9%+27.96%
      prior to the use of checklist and 80.05%+10.84% afterwards. Results of the
      independent t test for checklist scores showed that statistically significant
      differences were present between the SCA and non-SCA cases (t=5.88, df=18,
      p=0.000). CONCLUSION: Decision support tools can potentially increase the
      recognition rate of SCA cases, and therefore produce a higher rate of dispatcher
      directed CPR.

PMID- 28507998
TI  - Effects of Pre-Injury Anti-Platelet Agents on Short-Term Outcome of Patients with
      Mild Traumatic Brain Injury: A Cohort Study.
AB  - OBJECTIVE: To determine the effects of pre-injury consumption of anti-platelet
      agents on the 30-day outcomes of patients with mild traumatic brain injury (TBI).
      METHODS: This prospective cohort study was conducted at three general hospitals
      in Tehran, Iran between July 2013 and July 2014. The study population included
      all patients with mild TBI aged over 18 years that medicated with aspirin or
      clopidogrel before occurring trauma. Within hospitalization, all patients were
      assessed with respect to in-hospital conditions especially complications and
      adverse events. After discharge, the individuals were followed for 30 days by
      telephone to assess mortality and disability using the Glasgow outcome scale
      (GOS). RESULTS: Of 1140 patients with mild TBI, only 135 had previously received
      aspirin and/or clopidogrel. The mean age was dramatically higher in those who
      were taking aspirin or clopidogrel (p<0.001). The patients with previously use of
      anti-platelets were more transferred by ambulance when compared to another group
      (p=0.006). The patients on anti-platelets had significantly lower GCS on
      admission when compared to others (p<0.001). Length of hospitalization was
      significantly longer in those receiving anti-platelets (p=0.003). In follow-up,
      30-day mortality and disability was revealed in 2.8% of patients that received
      only aspirin and 7.5% in aspirin with clopidogrel and in 1.6 % of those who did
      not receive drugs without any significant difference between aspirin and control
      group (p=0.208) and significant difference in aspirin with clopidogrel group
      (p<0.001). CONCLUSION: The premedication by anti-platelets (aspirin and/or
      clopidogrel) in patients with mild TBI leads to prolonged hospital stay, and
      increase rate of disability. Age and on admission GCS are the independent risk
      factors for predicting the outcome in patients with mild TBI receiving anti
      platelet agents.

PMID- 28507999
TI  - Risk Factors of Road Traffic Accidents Associated Mortality in Northern Iran; A
      Single Center Experience Utilizing Oaxaca Blinder Decomposition.
AB  - OBJECTIVES: To investigate the differences in death after receiving emergency
      services in traffic accidents between urban and rural regions, and decompose
      factors of the gap in Langerood, Northern Iran. METHODS: This cross-sectional
      study was conducted in Langrood, Northern Iran during a 1-year period from 2013
      to 2014. The hospital data of traffic crashes were used. Data contained those
      patients who survived at the scene of accident. Injury severity score, time to
      admission, age, gender, season of crash and type of collision were variables used
      in this study. Oaxaca decomposition technique was used to show the amount of
      inequity. In addition, three regression models were used to show the reason of
      inequity. RESULTS: Overall 1520 patients with road traffic accidents were
      admitted to our center during the study period. The mean age of the patients was
      35.45 +/- 17.9 years, and there were 1158 (76.1 %) men among the victims.
      Motorbike accidents accounted for 869 (57.1%) injuries and 833 (54.8 %) accidents
      occurred in rural regions. The in-hospital mortality rate was 60 (3.9%). The
      results of this study showed that 95% of inequity came from factors used in this
      study and 2.04% disadvantages were for rural crashes. Severity of crash and time
      to admission had relationship with death, while the effects of time to admission
      was higher in rural region and severity of the accident had more effect on
      mortality in urban regions in comparison with rural ones. CONCLUSION: The high
      rate of fatal accidents could be decreased by deleting the gap of access to
      health care services between urban and rural regions. This study suggested that
      more efforts of health system are needed to reduce the gap.

PMID- 28508000
TI  - Knowledge and Attitude of Iranian Red Crescent Society Volunteers in Dealing with
      Chemical Attacks.
AB  - OBJECTIVE: To evaluate the knowledge, attitude, and preparedness of Mahabad Red
      Crescent Society volunteers in dealing with chemical attacks. METHODS: This
      prospective cross-sectional study was conducted on 120 Red Crescent Society
      volunteers in Mahabad City, Iran, during 2014-2015.The knowledge of the
      volunteers was evaluated and rated using a questionnaire as poor, moderate, and
      good. Also, the attitude of the volunteers towards the chemical attacks and their
      preparedness were rated as appropriate and inappropriate using a questionnaire.
      Data were analyzed using the SPSS software version 21. RESULTS: From a total of
      120 volunteers, 62.5% were males. The mean age of the volunteers was 32.0 +/- 8.2
      years. None of the volunteers had adequate knowledge regarding management of the
      consequences of chemical terrorist attacks. Only 10 volunteers (8.3%) had
      appropriate attitude and 7 (5.8%) stated their preparedness for being sent to the
      crisis zone. Also, 116 volunteers (96.7%) declared that Mahabad Red Crescent
      Society has an inappropriate level of preparedness to encounter chemical
      terrorism attacks and release of chemical agents related to petrochemical
      industrial chlorine resources into the water and wastewater. CONCLUSION: The
      findings of the present study show poor knowledge and inappropriate attitude of
      Mahabad Red Crescent Society volunteers, and rescuers in encountering probable
      chemical attacks and industrial accidents. Furthermore, the Red Crescent Society
      had an inappropriate level of preparedness in the field of chemical terrorism
      from the viewpoint of the studied volunteers.

PMID- 28508001
TI  - Closing a Tracheal Defect with an Omental Pedicled Gastric Flap; A Technical
      Note.
AB  - Due to an adenocarcinoma of the right upper lobe with infiltration of the main
      bronchus a 49-years-old female patient underwent an upper bilobectomy with sleeve
      resection. After two completed chemotherapy bouts and signs of sepsis another
      thoracotomy was inevitable.  As a complicating factor a supracarinal, necrotic
      and perforating lesion of the trachea appeared. The defect can be initially
      repaired with a suture and covered with azygos vein material. However surgical
      revision showed an enlargement of the tracheal necrosis. Then the lesion was
      occluded with a diaphragmatic pedicled flap. Nevertheless after the operation a
      tracheal insufficiency with massive ventilation leakage was observed. It was
      generated by the death of the diaphragmatic flap. As an ultimate therapeutic
      measure a transplantation of a pedicled omental gastric flap was performed, which
      in case of a failure of the conventional operative techniques, is an additional
      option in closing tracheal defects caused by infections. Especially in cases of
      massive infected thoracic cavity and tracheal necrosis omentum majus is, compared
      to muscle flaps, the better biological tissue to close and heal the tracheal
      defect. This case report firstly describes a successfully closure of a tracheal
      defect using the technique mentioned above.

PMID- 28508002
TI  - Postoperative Spontaneous Intussusception Caused by a Jejunal Peritoneal Cyst: A
      Case Report and Literature Review.
AB  - Postoperative intussusception in adults is an extremely rare clinical entity.
      Postoperative intussusception caused by a jejunal peritoneal cyst is even rarer.
      Etiopathogenesis of this clinical condition is not well understood. In the given
      case it seems to be a complication of prolonged contact of a draining tube with
      bowel. We present a case of postoperative spontaneous intussusception in a 72
      year-old female patient after gastric surgery. The cause of intussusception
      appeared to be a jejunal peritoneal cyst which is extremely rare. Desinvagination
      and excision of cyst via laparotomy was performed and the postoperative course
      was uneventful. Abdominal draining tubes should be placed in a position which
      will avoid possible further prolonged contact with bowel.

PMID- 28508003
TI  - Avoidance of 'Mishra Phenomenon' Prevents Technical Failure of Hepatic Artery
      Angioembolization following Failed Perihepatic Packing in Traumatic Liver Injury.

PMID- 28508005
TI  - An Unusual First Manifestation of Hodgkin Lymphoma: Epitrochlear Lymph Node
      Involvement-A Case Report and Brief Review of Literature.
AB  - Although epitrochlear lymph nodes may be enlarged as a part of generalized
      lymphadenopathy, isolated enlargement of epitrochlear lymph nodes is rarely seen.
      We describe Hodgkin's lymphoma in a 55-year-old male who presented with isolated
      epitrochlear lymphadenopathy of his right arm. In the histopathological
      examination of the epitrochlear lymph node was a lymphocyte-rich Hodgkin lymphoma
      with a clinical grade (CS IA) diagnosed. The diagnosis was confirmed, via the
      bone marrow biopsy and positron emission tomography/computed tomography imaging,
      as pathological stage PS IA and clinical stage CS IA. Epitrochlear lymph node
      involvement, as a first presentation, is rarely seen in Hodgkin's lymphoma. The
      aim of this study was to recapitulate the possible background diseases arising on
      the basis of an asymptomatic epitrochlear lymphadenopathy, to review the Hodgkin
      lymphoma presenting with primary epitrochlear lymphadenopathy in light of the
      literature, and to highlight the importance of a careful examination of the elbow
      site in routine physical examination.

PMID- 28508004
TI  - Tacrolimus-Associated Dilated Cardiomyopathy in Adult Patient After Orthotopic
      Liver Transplant.
AB  - This report presents a case of tacrolimus cardiotoxicity in an adult patient who
      received tacrolimus immunosuppression for orthotopic liver transplant (OLT).
      Tacrolimus-associated cardiotoxicity has been described in the literature,
      however this is the first case to document the development of a dilated
      cardiomyopathy in a patient shortly after initiating tacrolimus therapy post
      transplant. With the growing use of tacrolimus in transplant medicine, this case
      report expands the literature of tacrolimus cardiotoxicity and can aid clinicians
      in the evaluation and management of patients exposed to this form of
      immunosuppression.

PMID- 28508007
TI  - Five-Year Outcomes After Treatment for Acute Instability of the Tibiofibular
      Syndesmosis Using a Suture-Button Fixation System.
AB  - BACKGROUND: Suture-button repair is a widely accepted surgical treatment for
      acute and isolated ankle syndesmosis injuries. To our knowledge, midterm results
      have not previously been reported. PURPOSE: To evaluate the clinical,
      qualitative, and quantitative radiological midterm outcomes of suture-button
      repair after acute isolated ankle syndesmosis injuries. STUDY DESIGN:
      Retrospective case series; Level of evidence, 4. METHODS: Clinical outcomes were
      measured using the Foot and Ankle Disability Index (FADI) and the American
      Orthopaedic Foot and Ankle Society (AOFAS) score. Three-tesla magnetic resonance
      imaging (MRI) was performed bilaterally at the ankle. Besides morphological
      sequences for evaluation of the syndesmosis and degenerative changes of the ankle
      using the Ankle Osteoarthritis Scoring System (AOSS), the MR protocol included a
      coronal 2-dimensional multislice multiecho sequence for quantitative cartilage T2
      weighted mapping. Spearman correlations and paired t tests were used for
      statistical analysis. RESULTS: This retrospective study included 19 consecutive
      patients (mean age, 29.7 +/- 11.5 years) with acute isolated syndesmosis injuries
      treated with a suture-button system between January 2006 and June 2014, with a
      mean follow-up of 5.1 +/- 2.6 years. Postoperatively, the median FADI score was
      136 (range, 78-136), and the median AOFAS score was 100 (range, 87-100).
      Seventeen (89.5%) patients reported to have reached their preinjury level of
      sports activities. MRIs of 16 patients were obtained and all showed intact
      anterior and posterior syndesmotic ligaments; however, in most patients, the
      previously injured syndesmotic ligament was thickened compared with the uninjured
      ankle. Average width of the anterior (P = .81) and posterior (P = .60)
      syndesmosis was not significantly different between the ipsilateral (3.2 +/- 1.2
      and 4.4 +/- 0.9 mm) and contralateral ankles (3.0 +/- 0.6 and 4.2 +/- 0.7 mm).
      The median AOSS score was 1.5 (range, 0-11) for the ipsilateral ankle and 0
      (range, 0-6) for the contralateral ankle. T2 values of articular cartilage did
      not significantly differ between the involved and the uninjured ankle (P = .68).
      Five patients needed hardware removal due to persistent skin irritation, and 1
      patient suffered from reinstability of the ankle resulting in revision surgery 2
      years after the index surgery. CONCLUSION: Suture-button fixation is an excellent
      treatment for acute and isolated syndesmosis injuries, resulting in stable ankles
      without early or advanced osteoarthritic changes at midterm follow-up.

PMID- 28508006
TI  - Early Osteoarthritis After Untreated Anterior Meniscal Root Tears: An In Vivo
      Animal Study.
AB  - BACKGROUND: Meniscal root tears cause menisci and their insertions to
      inadequately distribute loads and potentially leave underlying articular
      cartilage unprotected. Untreated meniscal root tears are becoming increasingly
      recognized to induce joint degradation; however, little information is known
      about anterior meniscal root tears and how they affect joint tissue. PURPOSE: To
      observe the early degenerative changes within the synovial fluid, menisci, tibial
      articular cartilage, and subchondral bone after arthroscopic creation of
      untreated anterior meniscal root tears. STUDY DESIGN: Controlled laboratory
      study. METHODS: Anterolateral meniscal root tears were created in 1 knee joint of
      5 adult Flemish Giant rabbits, and anteromedial meniscal root tears were created
      in 4 additional rabbits. The contralateral limbs were used as nonoperated
      controls. The animals were euthanized at 8 weeks postoperatively; synovial fluid
      was aspirated, and tissue samples of menisci and tibial articular cartilage were
      collected and processed for multiple analyses to detect signs of early
      degeneration. RESULTS: Significant changes were found within the synovial fluid,
      meniscal tissue, and tibial subchondral bone of the knees with anterior meniscal
      root tears when compared with controls. There were no significant changes
      identified in the tibial articular cartilage when comparing the tear groups with
      controls. CONCLUSION: This study demonstrated early degenerative changes within
      the synovial fluid, menisci, and tibial subchondral bone when leaving anterior
      meniscal root tears untreated for 8 weeks. The results suggest that meniscal
      tissue presents measurable, degenerative changes prior to changes within the
      articular cartilage after anterior meniscal root tears. Anterior destabilization
      of the meniscus arthroscopically may lead to measurable degenerative changes and
      be useful for future in vivo natural history and animal repair studies. CLINICAL
      RELEVANCE: The present study is the first to investigate various tissue changes
      after anterior meniscal root tears of both the medial and lateral menisci. The
      results from this study suggest that degenerative changes occur within the
      synovial fluid, meniscus, and tibial subchondral bone prior to any measurable
      changes to the tibial articular cartilage. Further studies should expand on this
      study to evaluate how these components continue to progress when left untreated
      for long periods.

PMID- 28508009
TI  - Encephalomyelitis Following Definitive Zika Virus Infection.

PMID- 28508010
TI  - Spontaneous remission lasting more than a decade in untreated AQP4 antibody
      positive NMOSD.

PMID- 28508008
TI  - The Coracoacromial Ligament: Anatomy, Function, and Clinical Significance.
AB  - The coracoacromial ligament (CAL) was first described as a pain generator by Dr
      Charles Neer in the early 1970s. Since that time, considerable controversy
      regarding CAL management during acromioplasty has persisted. This review aims to
      better understand the role of the CAL in shoulder physiology and pathology. Sixty
      six articles from 1958 to 2016 were identified using an electronic search of
      PubMed, Cochrane Library, AccessMedicine, and MD Consult for case series as well
      as cohort and prospective studies. The authors used "coracoacromial ligament" and
      "coracoacromial veil" as medical subject headings (MeSH). In addition, reference
      lists from all identified articles were reviewed for studies that the search
      terms may have omitted. The CAL plays an important role in shoulder biomechanics,
      joint stability, and proprioception. Morphological variance of the CAL is evident
      throughout the literature. Age-dependent changes due to chronic stress and
      cellular degradation cause thickening and stiffening of the CAL that may
      contribute to a spectrum of shoulder pathology from capsular tightness to rotator
      cuff tear arthropathy and impingement syndrome. The CAL is an integral component
      of the coracoacromial arch. CAL release during acromioplasty remains
      controversial. Future clinical outcomes research should endeavor to advance the
      understanding of the CAL to refine clinical and intraoperative decision making
      regarding its management.

PMID- 28508011
TI  - Mandated Health Insurance and Provider Reimbursement via Private Insurance:
      Evidence From the Massachusetts Health Reform.
AB  - In 2006, Massachusetts passed a reform that required individuals to purchase
      health insurance and provided subsidized health insurance to low-income
      individuals. The US Patient Protection and Affordable Care Act (ACA) was modeled
      after this reform, making Massachusetts an ideal place to look at potential
      outcomes from the ACA. Postreform, the proportion of the health-insured
      population in Massachusetts greatly increased, which potentially changed
      physician reimbursement for procedures as usage of care, particularly
      preventative care for children increased. We find that reimbursement for well
      infant visits rose temporarily by approximately 4% the year after the reform but
      that the effective price increase did not persist. It is likely that this lack of
      persistence is due to an increase in the supply of physicians. This has important
      implications for the ACA, as expanding physician capacity is more difficult on a
      national level.

PMID- 28508012
TI  - Rehabilitation of Discharged Patients With Chronic Obstructive Pulmonary Disease
      Are New Strategies Needed?
AB  - BACKGROUND: Rehabilitation after hospital stay implies several benefits for
      patients with chronic obstructive pulmonary disease (COPD); still few patients
      are referred and participate in rehabilitation programs. We conducted a case
      study to investigate the effects of interventions targeting the referral, uptake,
      and completion for a program of early rehabilitation in the primary health-care
      sector. METHODS: We undertook targeted initiatives to make patients participate
      in an individualized rehabilitation program with gradual increased intensity.
      After discharge, primary care COPD nurses and physiotherapists guided patients
      through progressing exercises in small groups online. Patients proceeded to class
      based exercises, patient education and/or leisure activities, or continued
      telerehabilitation. We evaluated the effects of the intervention by assessing
      referral rates, completion, and readmission. RESULTS: Sixteen (23% of discharged
      patients) patients were referred to rehabilitation. In comparison, only 1 (0.8%)
      in 131 patients from Vejle hospital was referred to Vejle hospital. Twelve
      patients completed rehabilitation, all having severe COPD. All started the
      program within 2 weeks and proceeded to the online-guided exercises within 4
      weeks. Study data showed that after 30 days, 1 (6.3%) of the 16 patients in the
      rehabilitation program had been readmitted compared to 8 (14.8%) of 55 patients
      who were not referred. After 90 days, 2 (12.5%) and 11 (20.0%) patients were
      readmitted, respectively. The readmission rate showed a nonsignificant decline in
      patients participating in rehabilitation. CONCLUSION: This case study showed that
      the referral rate of patients with COPD to early municipal rehabilitation is
      extremely low without a targeted effort and still insufficient in spite of a
      focused intervention. We showed that completion of a municipal rehabilitation
      program shortly after discharge is possible even for patients with severe COPD.
      The findings from our pilot study can guide further investigations into the
      effect of implementation strategies for handovers between health-care sectors to
      secure early-onset rehabilitation of patients with COPD.

PMID- 28508013
TI  - Self-Reported Diagnosis of Type 1 and Type 2 Diabetes and Lifestyle Change Among
      Uninsured Primary Care Patients.
AB  - INTRODUCTION: The purpose of this study is to examine self-reported diagnosis of
      type 1 and type 2 diabetes and lifestyle change among uninsured primary care
      patients utilizing a free clinic. METHODS: Free clinic patients participated in a
      self-administered survey in May and June 2016. Patients with the following self
      reported diagnoses were analyzed: type 2 diabetes only (n = 84), and type 1
      diabetes only or both (n = 43). RESULTS: Participants who reported having type 2
      diabetes only and/or were patients of the diabetes clinic were less likely to
      have modified diet and/or physical activity to manage diabetes compared to those
      with type 1 diabetes and/or those who were not patients of the diabetes clinic.
      Participants with hypertension were more likely to have changed diet and/or
      physical activity compared to those without hypertension. CONCLUSION: Uninsured
      primary care patients may not know whether they have type 1 or type 2 diabetes.
      This is problematic as type 1 and type 2 diabetes require different prevention
      and self-management strategies. Future studies should examine the impact of
      misunderstanding the 2 types of diabetes on health behaviors and outcomes and
      explore the context of the misunderstanding.

PMID- 28508014
TI  - When Actions Speak Louder Than Words: Extending the Reach of Qualitative Data
      Collecting.
AB  - Through the lens of a study exploring dementia care partnering, the purpose of
      this methods article is to focus on the role of artifacts and embodied data in
      data collection. In addition, it illustrates how to use a range of data
      collecting methods. The article identifies benefits of additional data collecting
      methods to research and care. These include the need to expand data collecting
      methods beyond spoken word, integrate a range of data collecting approaches into
      research courses across disciplines, increase support of qualitative research,
      and advocate for greater inclusivity in research. Data collecting approaches can
      also have implications for quality of life among persons often excluded from
      research-building endeavors. They can contribute to the unfolding of new
      findings, which can influence care practices.

PMID- 28508015
TI  - Vaccine-Hesitant Justifications: "Too Many, Too Soon," Narrative Persuasion, and
      the Conflation of Expertise.
AB  - Vaccine-preventable diseases have re-emerged as more individuals have strayed
      from the recommended inoculation schedule. Previous work on vaccine hesitancy is
      generally limited to content analyses. Using grounded theory, this project
      examines vaccine debates on a prominent discussion board over a period of five
      years. Individuals generally justified opposition or hesitancy toward vaccines
      through personal experience and/or research, and the concepts of narrative
      persuasion and the conflation of expertise help describe the most prominent
      characteristics of such discourse. A consideration of online comments regarding
      vaccinations allows practitioners to not only become better prepared for patient
      concerns they might encounter, and but also become more familiar with the types
      of anecdotes and narratives that may be influential but left unspoken in face-to
      face conversations.

PMID- 28508016
TI  - Trust, Health Care Relationships, and Chronic Illness: A Theoretical Coalescence.
AB  - Trust in health care relationships is a key ingredient of effective, high-quality
      care. Although the indirect influence of trust on health outcomes has long been
      recognized, recent research has shown that trust has a direct effect on outcomes
      of care. Trust is important. However, the research on trust is disparate,
      organized around differing definitions, and primarily focused on patients' trust
      in physicians. Morse's method of theoretical coalescence was used to further
      develop and elaborate a grounded theory of the evolution of trust in health care
      relationships, in the context of chronic illness. This middle-range theory offers
      a clear conceptual framework for organizing and relating disparate studies,
      explaining the findings of different studies at a higher conceptual level, and
      identifying gaps in research and understanding. In addition, the grounded theory
      is relevant to practice.

PMID- 28508017
TI  - Caring for Clients and Families With Anxiety: Home Care Nurses' Practice
      Narratives.
AB  - This study elucidated Japanese home care nurses' experiences of supporting
      clients and families with anxiety. We interviewed 10 registered nurses working in
      home care agencies and analyzed the data using grounded theory to derive
      categories pertaining to the nurses' experiences of providing care. We
      conceptualized nurses' approaches to caring for anxiety into three categories:
      First, they attempted to reach out for anxiety even when the client/family did
      not make it explicit; second, they tried to alter the outlook of the situation;
      and third, they created comfort in the lives of the client/family. The
      conceptualizations of nurses' strategies to alleviate client/family anxiety may
      reflect Japanese/Eastern cultural characteristics in communication and their view
      of the person and social care system, but these conceptualizations may also
      inform the practice of Western nurses by increasing awareness of skills they may
      also have and use.

PMID- 28508018
TI  - Conflict and Care: Israeli Healthcare Providers and Syrian Patients and
      Caregivers in Israel.
AB  - Israel has provided immediate healthcare to Syrian children, civilians and
      fighters since early 2013 despite being in an official state of war with Syria
      since 1973. We present qualitative findings from a larger mixed-methods
      phenomenological study to understand how the geopolitical and social history of
      Israel and Syria influences healthcare providers and Syrian patient caregivers in
      northern Israel. Theories of humanization and cognitive dissonance guided this
      study and frame the beliefs and experiences of healthcare providers who treated
      wounded Syrians in Israeli hospitals. Findings indicate healthcare providers and
      Syrian caregivers adjusted their beliefs to allow for positive healthcare
      experiences. Qualitative analysis revealed two major themes: supportive and
      hindering systemic elements contributing to the healthcare provider-patient
      caregiver relationship. Internal psychological developments, contextual factors,
      and relational processes influenced humanization of the other within the
      relationship. This study illuminates unique ethical and humanitarian demands
      relevant for healthcare workers and those with whom they interact.

PMID- 28508019
TI  - "I Do It With Love": Engagement in Caring for People With Dementia.
AB  - For caregivers, the impacts of caring for their loved ones with dementia at home
      are complex. The purpose of this study was to gain understanding of the meaning
      and experience of engagement for caregivers of individuals with dementia living
      in the community. Participants are from a culturally diverse population of low
      income caregivers and care recipients in the northeastern United States. We
      conducted in-depth semi-structured interviews with caregivers (n = 17) who were
      caring for parents, friends, or other relatives with dementia. We used
      interpretative phenomenological analysis and identified the superordinate themes
      of connectedness, meaningfulness, acceptance, and vigilance. We conclude that
      caregiver engagement is a multidimensional phenomenon, with some dimensions being
      contextual and specific to caregiving. It is a relational concept, referring to a
      committed, vigilant, and meaningful relationship of caregivers and care
      recipients as active collaborators. The different aspects of engagement can
      complement each other, or they can be in contradiction.

PMID- 28508020
TI  - Birth Care Providers' Experiences and Practices in a Brazilian Alongside
      Midwifery Unit: An Ethnographic Study.
AB  - The implementation of a new birthing facility in a country such as Brazil
      requires an extensive in-depth analysis of the challenges faced. The aim of this
      study was to explore beliefs, values, experiences, and practices related to the
      provision of birthing and neonatal care with the implementation of a new birth
      care facility structure called alongside midwifery units in Brazil. The study
      utilizes an ethnographic method to evaluate members of a Brazilian public
      hospital's midwifery unit. The ethnographic study focuses on the cultural theme
      of "between the proposed and the possible": the following birthing care
      guidelines require overcoming numerous obstacles, and four other cultural
      subthemes toward revealing the analyzed birth care team's perspectives. The study
      found that prior training and preparation of all members of the care team, as
      well as the provision of adequate institutional infrastructure are essential for
      the implementation of a new and innovative birthing care center.

PMID- 28508021
TI  - Examining the Roles and Experiences of Fathers of Children With Chronic Kidney
      Disease.
AB  - This study examined roles and experiences of fathers of children with chronic
      kidney disease (CKD). Based on interpretive description, semistructured
      interviews were conducted with 22 fathers of children receiving a range of
      treatments (transplant, peritoneal dialysis, hemodialysis, and CKD not requiring
      renal replacement therapy). Fathers described various experiences and means of
      adjusting to shifts associated with pediatric CKD. These included loss of
      personal control, a sense of personal isolation, and a stance of remaining strong
      amidst personal suffering. Nuanced differences according to modality of CKD care
      were identified. Fathers engaged in strategies that fostered coping, such as
      remaining positive and taking charge. They conveyed deep love for their child,
      and demonstrated ingenuity and persistence in care. Few resources of support were
      accessed by fathers. Study recommendations invite holistic approaches to health
      care, with improved resources for families-including fathers-in addressing the
      needs of this population.

PMID- 28508022
TI  - Impact of Health Literacy on Senior Citizen Engagement in Health Care IT Usage.
AB  - Objective: Patient engagement in health care information technology (IT) is
      required for government reimbursement programs. This research surveyed one older
      adult group to determine their willingness to use health information from a
      variety of sources. Health literacy was also measured using the Newest Vital Sign
      (NVS) and eHealth Literacy Scale (eHEALS) tools. Method: Regression models
      determined engagement in health care IT usage and impact of literacy levels based
      on survey data collected from the group. Results: Although most participants have
      adequate literacy, they are not more likely to use health care IT than those with
      limited literacy scores. Knowledge of how to use the Internet to answer questions
      about health was statistically associated with IT usage. Discussion: Health care
      IT usage is important for healthy aging. The ability of older adults to
      understand information provided to them can impact population health including
      medication usage and other important factors.

PMID- 28508023
TI  - An unusual presentation of LCAT deficiency as nephrotic syndrome with normal
      serum HDL-C level.
AB  - Clinical and biochemical manifestations of lecithin-cholesterol acyltransferase
      (LCAT) deficiency include an abnormal lipid profile (characterized by
      hypercholesterolemia with markedly decreased high-density lipoprotein cholesterol
      [HDL-C] and hypertriglyceridemia), corneal opacities, hematologic abnormalities
      (normochromic anemia of varying intensity), splenomegaly, variable early coronary
      artery disease and nephropathy (initially proteinuria followed by progressive
      deterioration of renal function). We presented a patient with nephrotic syndrome,
      which renal biopsy revealed classic features of LCAT deficiency. To our
      knowledge, the present case is the first reported case of LCAT deficiency
      presenting with symptoms related to nephrotic syndrome in a patient with no
      obvious family history without any corneal deposits and normal HDL-C levels.

PMID- 28508025
TI  - Graphical coding data and operational guidance for implementation or modification
      of a LabVIEW(r)-based pHstat system for the cultivation of microalgae.
AB  - The influence of pH on phytoplankton physiology is an important facet of the body
      of research on ocean acidification. We provide data developed during the design
      and implementation of a novel pHstat system capable of maintaining both static
      and dynamic pH environments in a laboratory setting. These data both help improve
      functionality of the system, and provide specific coding blocks for controlling
      the pHstat using a LabVIEW(r) virtual instrument (VI). The data in this paper
      support the research article "Development of an economical, autonomous pHstat
      system for culturing phytoplankton under steady state or dynamic conditions"
      (Golda et al. [2]). These data will be of interest to researchers studying the
      effects of changing pH on phytoplankton in a laboratory context, and to those
      desiring to build their own pHstat system(s). These data can also be used to
      facilitate modification of the pHstat system to control salinity, temperature, or
      other environmental factors.

PMID- 28508024
TI  - Pilot study of endoscopic retrograde 3-dimensional - computed tomography
      enteroclysis for the assessment of Crohn's disease.
AB  - PURPOSE: Endoscopic retrograde ileography (ERIG) is developed in our institute
      and applied clinically for the diagnosis and assessment of the Crohn's disease
      activity. We have further improved the technique using 3-dimensional - computed
      tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine
      the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D
      CTE) in Crohn's disease patients in a state of remission. METHODS: Thirteen
      Crohn's patients were included in this pilot study. CTE was performed after the
      infusion of air or CO2 through the balloon tube following conventional
      colonoscopy. The primary endpoint of this study was to assess the safety of this
      method. Secondarily, the specific findings of Crohn's disease and length of the
      visualized small intestine were assessed. RESULTS: The procedures were completed
      without any adverse events. Gas passed through the small intestine and
      enterographic images were obtained in 10 out of 13 cases, but, in the remaining
      patients, insertion of the balloon tubes into the terminal ileum failed. Various
      features specific to Crohn's disease were visualized using ER 3D-CTE. A cobble
      stone appearance or hammock-like malformation was specific and effective for
      diagnosing Crohn's disease and the features of anastomosis after the surgical
      operations were also well described. Therefore, this technique may be useful
      after surgery. CONCLUSION: In this study, ER 3D-CTE was performed safely in
      Crohn's disease patients and may be used for the diagnosis and follow-up of this
      disease.

PMID- 28508027
TI  - Violent actions against children.
AB  - We present in this paper a novel dataset (MMU VAAC) for violent actions against
      children recognition. This original dataset has been recorded using Microsoft
      Kinect with the usage of a child mannequin. MMU VAAC dataset contains skeleton
      joints, depth, and RGB modalities.

PMID- 28508026
TI  - Fluoride ion adsorption onto palm stone: Optimization through response surface
      methodology, isotherm, and adsorbent characteristics data.
AB  - In some part of the world, groundwater source can become unsafe for drinking due
      to the high concentration of fluoride ions [1]. The low cost and facile-produced
      adsorbent like palm stone could effectively removed fluoride ions through
      adsorption process. In this dataset, the influence of fluoride ion concentration,
      solution pH, adsorbent dosage, and contact time on fluoride ion adsorption by
      palm stones was tested by central composite design (CCD) under response surface
      methodology (RSM). The data stone carbonized adsorbent was prepared by a simple
      and facile method at relatively low temperature of 250  degrees C during 3 h. The
      adsorbent had the main functional groups of O-H, -OH, Si-H, C=O, N=O, C-C, C-OR,
      C-H, and C-Br on its surface. At the optimized conditions obtained by RSM, about
      84.78% of fluoride ion was removed using the adsorbent. The Langmuir isotherm was
      suitable for correlation of equilibrium data (maximum adsorption capacity= 3.95
      mg/g). Overall, the data offer a facile adsorbent to water and wastewater works
      which face to high level of fluoride water/ wastewater content.

PMID- 28508028
TI  - Data in support of poisoning related mortalities from southern Himachal Pradesh.
AB  - Poisoning has always been pointed as one of the leading causes of human death
      throughout the world. Despite the best efforts made by many research institutes,
      the worldwide true figure on mortalities with poisoning could never be achieved
      due to many reasons. One of the main reasons is the unavailability of complete
      database from the rural and catchment areas of the world where these types of
      incidents are usual. People can be made aware about this problem by presenting
      data articles on regular basis, therefore to mark a resource document these data
      should be regularly up-dated. The current data report is a briefing of types and
      trends of chemical poisoning amongst human in southern hilly region of Himachal
      Pradesh (HP), India. This research database is an outcome of five year
      retrospective study based on assessment of records pertaining human deaths
      associated with poisoning occurred in southern Himachal Pradesh, and reported at
      State Forensic Science Laboratory (SFSL), Junga during 2010-14. Cases where ethyl
      alcohol was detected have been put under exclusion criterion. All the cases were
      reviewed and summarized in terms of yearly and monthly frequency of reports
      wrapping important information portraying the involvement of gender, age,
      locality, types of poison, and mode of death in the poisoning incidents. Review
      of these scientific reports showed some notable figures having a direct concern
      with public and legal domains to promote risk reduction and prevention of
      chemical poisonings.

PMID- 28508030
TI  - Incidental leiomyosarcoma found at the time of cesarean hysterectomy for morbidly
      adherent placenta.
AB  - BACKGROUND: Incidental leiomyosarcoma (LMS) is a rare diagnosis in pregnancy or
      in the puerperium. To our knowledge, this is the first case reported in the
      literature of incidental LMS after cesarean hysterectomy for morbidly adherent
      placenta. CASE: We present a case of a cesarean hysterectomy performed for a
      suspected morbidly adherent placenta in a patient with three prior cesarean
      deliveries, an anterior placenta previa and a fundal fibroid. Subsequent
      pathology identified a LMS on final specimen. The patient declined bilateral
      oophorectomy and removal of her remaining cervix. No chemotherapy or radiation
      was given for her presumed stage IB disease. CONCLUSION: An incidental finding of
      a LMS is infrequent; the risk of recurrence is > 50% even if the sarcoma is
      removed in its entirety.

PMID- 28508029
TI  - A B-Cell Gene Signature Correlates With the Extent of Gluten-Induced Intestinal
      Injury in Celiac Disease.
AB  - BACKGROUND & AIMS: Celiac disease (CeD) provides an opportunity to study
      autoimmunity and the transition in immune cells as dietary gluten induces small
      intestinal lesions. METHODS: Seventy-three celiac disease patients on a long
      term, gluten-free diet ingested a known amount of gluten daily for 6 weeks. A
      peripheral blood sample and intestinal biopsy specimens were taken before and 6
      weeks after initiating the gluten challenge. Biopsy results were reported on a
      continuous numeric scale that measured the villus-height-to-crypt-depth ratio to
      quantify gluten-induced intestinal injury. Pooled B and T cells were isolated
      from whole blood, and RNA was analyzed by DNA microarray looking for changes in
      peripheral B- and T-cell gene expression that correlated with changes in villus
      height to crypt depth, as patients maintained a relatively healthy intestinal
      mucosa or deteriorated in the face of a gluten challenge. RESULTS: Gluten
      dependent intestinal damage from baseline to 6 weeks varied widely across all
      patients, ranging from no change to extensive damage. Genes differentially
      expressed in B cells correlated strongly with the extent of intestinal damage. A
      relative increase in B-cell gene expression correlated with a lack of sensitivity
      to gluten whereas their relative decrease correlated with gluten-induced mucosal
      injury. A core B-cell gene module, representing a subset of B-cell genes
      analyzed, accounted for the correlation with intestinal injury. CONCLUSIONS:
      Genes comprising the core B-cell module showed a net increase in expression from
      baseline to 6 weeks in patients with little to no intestinal damage, suggesting
      that these individuals may have mounted a B-cell immune response to maintain
      mucosal homeostasis and circumvent inflammation. DNA microarray data were
      deposited at the GEO repository (accession number: GSE87629; available:
      https://www.ncbi.nlm.nih.gov/geo/).

PMID- 28508032
TI  - What is the ideal timing for endoscopy in acute upper gastrointestinal bleeding?

PMID- 28508033
TI  - Over-the-scope clip (OTSC) reduces surgery rate in the management of iatrogenic
      gastrointestinal perforations.
AB  - Background and study aims Over-the-scope clip (OTSC) has been recently used in
      management of gastrointestinal perforations, but data on it are still limited.
      The aim of this study was to compare management of iatrogenic perforations before
      and after the OTSC was available in our endoscopy unit. Patients and methods We
      conducted a monocentric retrospective study from June 2007 to June 2015. All
      iatrogenic gastrointestinal perforations detected during endoscopy were included.
      Two time periods were compared in terms of surgery and mortality rates: before
      use of OTSC (June 2007 to June 2011) and after OTSC became available (June 2011
      to June 2015). Results During the first period, 24 perforations were recorded.
      Fifteen (62.5 %) were managed with surgery. The mortality rate was 8 %. During
      the second period, 16 perforations occurred. In 11 patients (68.7 %), an OTSC was
      used to close the perforation, with complete sealing of the perforation in 100 %
      of cases. However, 2 patients with sigmoid perforation had to undergo surgery due
      to right ureteral obstruction by the clip in 1 case and to presence of a
      localized peritonitis in the other. The surgery rate during this period was 12.5
      % (2 /16), with a statistically significant difference compared to the first
      period (P = 0.002). There was no mortality in the second period versus 8 % in the
      first one (P = 0.23). Conclusions OTSC is effective for endoluminal closure of
      iatrogenic perforations and results in a significant decrease in surgery rate.

PMID- 28508031
TI  - Altered levels of blood proteins in Alzheimer's disease longitudinal study:
      Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort.
AB  - INTRODUCTION: A blood-based biomarker panel to identify individuals with
      preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first
      step for routine testing. METHODS: We analyzed 14 biomarkers that have previously
      been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal
      study of aging cohort. RESULTS: Levels of apolipoprotein J (apoJ) were higher in
      AD individuals compared with healthy controls at baseline and 18 months (P =
      .0003) and chemokine-309 (I-309) were increased in AD patients compared to mild
      cognitive impaired individuals over 36 months (P = .0008). DISCUSSION: These data
      suggest that apoJ may have potential in the context of use (COU) of AD
      diagnostics, I-309 may be specifically useful in the COU of identifying
      individuals at greatest risk for progressing toward AD. This work takes an
      initial step toward identifying blood biomarkers with potential use in the
      diagnosis and prognosis of AD and should be validated across other prospective
      cohorts.

PMID- 28508034
TI  - Laminar Localization and Projection-Specific Properties of Presubicular Neurons
      Targeting the Lateral Mammillary Nucleus, Thalamus, or Medial Entorhinal Cortex.
AB  - The presubiculum (PrS) is part of an interconnected network of distributed brain
      regions where individual neurons signal the animals heading direction. PrS sends
      axons to medial entorhinal cortex (MEC), it is reciprocally connected with
      anterior thalamic nuclei (ATNs), and it sends feedback projections to the lateral
      mammillary nucleus (LMN), involved in generating the head direction signal. The
      intrinsic properties of projecting neurons will influence the pathway-specific
      transmission of activity. Here, we used projection-specific labeling of
      presubicular neurons to identify MEC-, LMN-, and ATN-projecting neurons in mice.
      MEC-projecting neurons located in superficial layers II/III were mostly regular
      spiking pyramidal neurons, and we also identified a Martinotti-type GABAergic
      neuron. The cell bodies of LMN-projecting neurons were located in a well
      delimited area in the middle portion of the PrS, which corresponds to layer IV.
      The physiology of LMN projecting, pyramidal neurons stood out with a tendency to
      fire in bursts of action potentials (APs) with rapid onset. These properties may
      be uniquely adapted to reliably transmit visual landmark information with short
      latency to upstream LMN. Neurons projecting to ATN were located in layers V/VI,
      and they were mostly regular spiking pyramidal neurons. Unsupervised cluster
      analysis of intrinsic properties suggested distinct physiological features for
      the different categories of projection neurons, with some similarities between
      MEC- and ATN-projecting neurons. Projection-specific subpopulations may serve
      separate functions in the PrS and may be engaged differently in transmitting head
      direction related information.

PMID- 28508037
TI  - Arctic greening from warming promotes declines in caribou populations.
AB  - The migratory tundra caribou herds in North America follow decadal population
      cycles, and browsing from abundant caribou could be expected to counteract the
      current climate-driven expansion of shrubs in the circumpolar tundra biome. We
      demonstrate that the sea ice cover in the Arctic Ocean has provided a strong
      signal for climate-induced changes on the adjacent caribou summer ranges,
      outperforming other climate indices in explaining the caribou-plant dynamics. We
      found no evidence of a negative effect of caribou abundance on vegetation
      biomass. On the contrary, we found a strong bottom-up effect in which a warmer
      climate related to diminishing sea ice has increased the plant biomass on the
      summer pastures, along with a paradoxical decline in caribou populations. This
      result suggests that this climate-induced greening has been accompanied by a
      deterioration of pasture quality. The shrub expansion in Arctic North America
      involves plant species with strong antibrowsing defenses. Our results might
      therefore be an early signal of a climate-driven shift in the caribou-plant
      interaction from a system with low plant biomass modulated by cyclic caribou
      populations to a system dominated by nonedible shrubs and diminishing herds of
      migratory caribou.

PMID- 28508038
TI  - Origami by frontal photopolymerization.
AB  - Origami structures are of great interest in microelectronics, soft actuators,
      mechanical metamaterials, and biomedical devices. Current methods of fabricating
      origami structures still have several limitations, such as complex material
      systems or tedious processing steps. We present a simple approach for creating
      three-dimensional (3D) origami structures by the frontal photopolymerization
      method, which can be easily implemented by using a commercial projector. The
      concept of our method is based on the volume shrinkage during
      photopolymerization. By adding photoabsorbers into the polymer resin, an
      attenuated light field is created and leads to a nonuniform curing along the
      thickness direction. The layer directly exposed to light cures faster than the
      next layer; this nonuniform curing degree leads to nonuniform curing-induced
      volume shrinkage. This further introduces a nonuniform stress field, which drives
      the film to bend toward the newly formed side. The degree of bending can be
      controlled by adjusting the gray scale and the irradiation time, an easy approach
      for creating origami structures. The behavior is examined both experimentally and
      theoretically. Two methods are also proposed to create different types of 3D
      origami structures.

PMID- 28508036
TI  - Room temperature stable CO x -free H2 production from methanol with magnesium
      oxide nanophotocatalysts.
AB  - Methanol, which contains 12.6 weight percent hydrogen, is a good hydrogen storage
      medium because it is a liquid at room temperature. However, by releasing the
      hydrogen, undesirable CO and/or CO2 byproducts are formed during catalytic fuel
      reforming. We show that alkaline earth metal oxides, in our case MgO
      nanocrystals, exhibit stable photocatalytic activity for CO/CO2-free H2
      production from liquid methanol at room temperature. The performance of MgO
      nanocrystals toward methanol dehydrogenation increases with time and approaches
      ~320 MUmol g-1 hour-1 after a 2-day photocatalytic reaction. The CO x -free H2
      production is attributed to methanol photodecomposition to formaldehyde,
      photocatalyzed by surface electronic states of unique monodispersed, porous MgO
      nanocrystals, which were synthesized with a novel facile colloidal chemical
      strategy. An oxygen plasma treatment allows for the removal of organic
      surfactants, producing MgO nanocrystals that are well dispersible in methanol.

PMID- 28508035
TI  - Flashing Lights Induce Prolonged Distortions in Visual Cortical Responses and
      Visual Perception.
AB  - The primary sensory neocortex generates an internal representation of the
      environment, and its circuit reorganization is thought to lead to a modification
      of sensory perception. This reorganization occurs primarily through activity
      dependent plasticity and has been well documented in animals during early
      developmental stages. Here, we describe a new method for the noninvasive
      induction of long-term plasticity in the mature brain: simple transient visual
      stimuli (i.e., flashing lights) can be used to induce prolonged modifications in
      visual cortical processing and visually driven behaviors. Our previous studies
      have shown that, in the primary visual cortex (V1) of mice, a flashing light
      stimulus evokes a long-delayed response that persists for seconds. When the mice
      were repetitively presented with drifting grating stimuli (conditioned stimuli)
      during the flash stimulus-evoked delayed response period, the V1 neurons
      exhibited a long-lasting decrease in responsiveness to the conditioned stimuli.
      The flash stimulus-induced underrepresentation of the grating motion was specific
      to the direction of the conditioned stimuli and was associated with a decrease in
      the animal's ability to detect the motion of the drifting gratings. The
      neurophysiological and behavioral plasticity both persisted for at least several
      hours and required N-methyl-d-aspartate receptor activation in the visual cortex.
      We propose that flashing light stimuli can be used as an experimental tool to
      investigate the visual function and plasticity of neuronal representations and
      perception after a critical period of neocortical plasticity.

PMID- 28508040
TI  - Quantum imaging of current flow in graphene.
AB  - Since its first discovery in 2004, graphene has been found to host a plethora of
      unusual electronic transport phenomena, making it a fascinating system for
      fundamental studies in condensed matter physics as well as offering tremendous
      opportunities for future electronic and sensing devices. Typically, electronic
      transport in graphene has been investigated via resistivity measurements;
      however, these measurements are generally blind to spatial information critical
      to observing and studying landmark transport phenomena in real space and in
      realistic imperfect devices. We apply quantum imaging to the problem and
      demonstrate noninvasive, high-resolution imaging of current flow in monolayer
      graphene structures. Our method uses an engineered array of near-surface, atomic
      sized quantum sensors in diamond to map the vector magnetic field and reconstruct
      the vector current density over graphene geometries of varying complexity, from
      monoribbons to junctions, with spatial resolution at the diffraction limit and a
      projected sensitivity to currents as small as 1 MUA. The measured current maps
      reveal strong spatial variations corresponding to physical defects at the
      submicrometer scale. The demonstrated method opens up an important new avenue to
      investigate fundamental electronic and spin transport in graphene structures and
      devices and, more generally, in emerging two-dimensional materials and thin-film
      systems.

PMID- 28508039
TI  - Naturally acidified habitat selects for ocean acidification-tolerant mussels.
AB  - Ocean acidification severely affects bivalves, especially their larval stages.
      Consequently, the fate of this ecologically and economically important group
      depends on the capacity and rate of evolutionary adaptation to altered ocean
      carbonate chemistry. We document successful settlement of wild mussel larvae
      (Mytilus edulis) in a periodically CO2-enriched habitat. The larval fitness of
      the population originating from the CO2-enriched habitat was compared to the
      response of a population from a nonenriched habitat in a common garden
      experiment. The high CO2-adapted population showed higher fitness under elevated
      Pco2 (partial pressure of CO2) than the non-adapted cohort, demonstrating, for
      the first time, an evolutionary response of a natural mussel population to ocean
      acidification. To assess the rate of adaptation, we performed a selection
      experiment over three generations. CO2 tolerance differed substantially between
      the families within the F1 generation, and survival was drastically decreased in
      the highest, yet realistic, Pco2 treatment. Selection of CO2-tolerant F1 animals
      resulted in higher calcification performance of F2 larvae during early shell
      formation but did not improve overall survival. Our results thus reveal
      significant short-term selective responses of traits directly affected by ocean
      acidification and long-term adaptation potential in a key bivalve species.
      Because immediate response to selection did not directly translate into increased
      fitness, multigenerational studies need to take into consideration the
      multivariate nature of selection acting in natural habitats. Combinations of
      short-term selection with long-term adaptation in populations from CO2-enriched
      versus nonenriched natural habitats represent promising approaches for estimating
      adaptive potential of organisms facing global change.

PMID- 28508042
TI  - Toward continuous-wave operation of organic semiconductor lasers.
AB  - The demonstration of continuous-wave lasing from organic semiconductor films is
      highly desirable for practical applications in the areas of spectroscopy, data
      communication, and sensing, but it still remains a challenging objective. We
      report low-threshold surface-emitting organic distributed feedback lasers
      operating in the quasi-continuous-wave regime at 80 MHz as well as under long
      pulse photoexcitation of 30 ms. This outstanding performance was achieved using
      an organic semiconductor thin film with high optical gain, high photoluminescence
      quantum yield, and no triplet absorption losses at the lasing wavelength combined
      with a mixed-order distributed feedback grating to achieve a low lasing
      threshold. A simple encapsulation technique greatly reduced the laser-induced
      thermal degradation and suppressed the ablation of the gain medium otherwise
      taking place under intense continuous-wave photoexcitation. Overall, this study
      provides evidence that the development of a continuous-wave organic semiconductor
      laser technology is possible via the engineering of the gain medium and the
      device architecture.

PMID- 28508044
TI  - Data-driven discovery of partial differential equations.
AB  - We propose a sparse regression method capable of discovering the governing
      partial differential equation(s) of a given system by time series measurements in
      the spatial domain. The regression framework relies on sparsity-promoting
      techniques to select the nonlinear and partial derivative terms of the governing
      equations that most accurately represent the data, bypassing a combinatorially
      large search through all possible candidate models. The method balances model
      complexity and regression accuracy by selecting a parsimonious model via Pareto
      analysis. Time series measurements can be made in an Eulerian framework, where
      the sensors are fixed spatially, or in a Lagrangian framework, where the sensors
      move with the dynamics. The method is computationally efficient, robust, and
      demonstrated to work on a variety of canonical problems spanning a number of
      scientific domains including Navier-Stokes, the quantum harmonic oscillator, and
      the diffusion equation. Moreover, the method is capable of disambiguating between
      potentially nonunique dynamical terms by using multiple time series taken with
      different initial data. Thus, for a traveling wave, the method can distinguish
      between a linear wave equation and the Korteweg-de Vries equation, for instance.
      The method provides a promising new technique for discovering governing equations
      and physical laws in parameterized spatiotemporal systems, where first-principles
      derivations are intractable.

PMID- 28508041
TI  - Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription
      and trigger free radical-induced DNA damage.
AB  - Breakage of one strand of DNA is the most common form of DNA damage. Most damaged
      DNA termini require end-processing in preparation for ligation. The importance of
      this step is highlighted by the association of defects in the 3'-end processing
      enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the
      cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid
      intermediates during chemotherapy and radiotherapy. Although much is known about
      the repair of PDBs in the nucleus, little is known about this process in the
      mitochondria. We reveal that TDP1 resolves mitochondrial PDBs (mtPDBs), thereby
      promoting mitochondrial gene transcription. Overexpression of a toxic form of
      mitochondrial topoisomerase I (TOP1mt*), which generates excessive mtPDBs,
      results in a TDP1-dependent compensatory up-regulation of mitochondrial gene
      transcription. In the absence of TDP1, the imbalance in transcription of
      mitochondrial- and nuclear-encoded electron transport chain (ETC) subunits
      results in misassembly of ETC complex III. Bioenergetics profiling further
      reveals that TDP1 promotes oxidative phosphorylation under both basal and high
      energy demands. It is known that mitochondrial dysfunction results in free
      radical leakage and nuclear DNA damage; however, the detection of intermediates
      of radical damage to DNA is yet to be shown. Consequently, we report an increased
      accumulation of carbon-centered radicals in cells lacking TDP1, using electron
      spin resonance spectroscopy. Overexpression of the antioxidant enzyme superoxide
      dismutase 1 (SOD1) reduces carbon-centered adducts and protects TDP1-deficient
      cells from oxidative stress. Conversely, overexpression of the amyotrophic
      lateral sclerosis-associated mutant SOD1G93A leads to marked sensitivity. Whereas
      Tdp1 knockout mice develop normally, overexpression of SOD1G93A suggests early
      embryonic lethality. Together, our data show that TDP1 resolves mtPDBs, thereby
      regulating mitochondrial gene transcription and oxygen consumption by oxidative
      phosphorylation, thus conferring cellular protection against reactive oxygen
      species-induced damage.

PMID- 28508045
TI  - Experimental demonstration of nonbilocal quantum correlations.
AB  - Quantum mechanics admits correlations that cannot be explained by local realistic
      models. The most studied models are the standard local hidden variable models,
      which satisfy the well-known Bell inequalities. To date, most works have focused
      on bipartite entangled systems. We consider correlations between three parties
      connected via two independent entangled states. We investigate the new type of so
      called "bilocal" models, which correspondingly involve two independent hidden
      variables. These models describe scenarios that naturally arise in quantum
      networks, where several independent entanglement sources are used. Using photonic
      qubits, we build such a linear three-node quantum network and demonstrate
      nonbilocal correlations by violating a Bell-like inequality tailored for bilocal
      models. Furthermore, we show that the demonstration of nonbilocality is more
      noise-tolerant than that of standard Bell nonlocality in our three-party quantum
      network.

PMID- 28508043
TI  - Crystal structure of 2C helicase from enterovirus 71.
AB  - Enterovirus 71 (EV71) is the major pathogen responsible for outbreaks of hand,
      foot, and mouth disease. EV71 nonstructural protein 2C participates in many
      critical events throughout the virus life cycle; however, its precise role is not
      fully understood. Lack of a high-resolution structure made it difficult to
      elucidate 2C activity and prevented inhibitor development. We report the 2.5 A
      resolution crystal structure of the soluble part of EV71 2C, containing an
      adenosine triphosphatase (ATPase) domain, a cysteine-rich zinc finger with an
      unusual fold, and a carboxyl-terminal helical domain. Unlike other AAA+ ATPases,
      EV71 2C undergoes a carboxyl terminus-mediated self-oligomerization, which is
      dependent on a specific interaction between the carboxyl-terminal helix of one
      monomer and a deep pocket formed between the ATPase and the zinc finger domains
      of the neighboring monomer. The carboxyl terminus-mediated self-oligomerization
      is fundamental to 2C ATPase activity and EV71 replication. Our findings suggest a
      strategy for inhibition of enterovirus replication by disruption of the self
      oligomerization interface of 2C.

PMID- 28508046
TI  - Carbon-free H2 production from ammonia triggered at room temperature with an
      acidic RuO2/gamma-Al2O3 catalyst.
AB  - Ammonia has been suggested as a carbon-free hydrogen source, but a convenient
      method for producing hydrogen from ammonia with rapid initiation has not been
      developed. Ideally, this method would require no external energy input. We
      demonstrate hydrogen production by exposing ammonia and O2 at room temperature to
      an acidic RuO2/gamma-Al2O3 catalyst. Because adsorption of ammonia onto the
      catalyst is exothermic, the catalyst bed is rapidly heated to the catalytic
      ammonia autoignition temperature, and subsequent oxidative decomposition of
      ammonia produces hydrogen. A differential calorimeter combined with a volumetric
      gas adsorption analyzer revealed a large quantity of heat evolved both with
      chemisorption of ammonia onto RuO2 and acidic sites on the gamma-Al2O3 and with
      physisorption of multiple ammonia molecules.

PMID- 28508047
TI  - Kin-based cultural transmission of tool use in wild chimpanzees.
AB  - Current research on animal culture has focused strongly on cataloging the
      diversity of socially transmitted behaviors and on the social learning mechanisms
      that sustain their spread. Comparably less is known about the persistence of
      cultural behavior following innovation in groups of wild animals. We present
      observational data and a field experiment designed to address this question in a
      wild chimpanzee community, capitalizing on a novel tool behavior, moss-sponging,
      which appeared naturally in the community in 2011. We found that, 3 years later,
      moss-sponging was still present in the individuals that acquired the behavior
      shortly after its emergence and that it had spread further, to other community
      members. Our field experiment suggests that this secondary radiation and
      consolidation of moss-sponging is the result of transmission through matrilines,
      in contrast to the previously documented association-based spread among the
      initial cohort. We conclude that the spread of cultural behavior in wild
      chimpanzees follows a sequential structure of initial proximity-based horizontal
      transmission followed by kin-based vertical transmission.

PMID- 28508048
TI  - Optical identification of sulfur vacancies: Bound excitons at the edges of
      monolayer tungsten disulfide.
AB  - Defects play a significant role in tailoring the optical properties of two
      dimensional materials. Optical signatures of defect-bound excitons are important
      tools to probe defective regions and thus interrogate the optical quality of as
      grown semiconducting monolayer materials. We have performed a systematic study of
      defect-bound excitons using photoluminescence (PL) spectroscopy combined with
      atomically resolved scanning electron microscopy and first-principles
      calculations. Spatially resolved PL spectroscopy at low temperatures revealed
      bound excitons that were present only on the edges of monolayer tungsten
      disulfide and not in the interior. Optical pumping of the bound excitons was
      sublinear, confirming their bound nature. Atomic-resolution images reveal that
      the areal density of monosulfur vacancies is much larger near the edges (0.92 +/-
      0.45 nm-2) than in the interior (0.33 +/- 0.11 nm-2). Temperature-dependent PL
      measurements found a thermal activation energy of ~36 meV; surprisingly, this is
      much smaller than the bound-exciton binding energy of ~300 meV. We show that this
      apparent inconsistency is related to a thermal dissociation of the bound exciton
      that liberates the neutral excitons from negatively charged point defects. First
      principles calculations confirm that sulfur monovacancies introduce midgap states
      that host optical transitions with finite matrix elements, with emission energies
      ranging from 200 to 400 meV below the neutral-exciton emission line. These
      results demonstrate that bound-exciton emission induced by monosulfur vacancies
      is concentrated near the edges of as-grown monolayer tungsten disulfide.

PMID- 28508049
TI  - Mechanism and color modulation of fungal bioluminescence.
AB  - Bioluminescent fungi are spread throughout the globe, but details on their
      mechanism of light emission are still scarce. Usually, the process involves three
      key components: an oxidizable luciferin substrate, a luciferase enzyme, and a
      light emitter, typically oxidized luciferin, and called oxyluciferin. We report
      the structure of fungal oxyluciferin, investigate the mechanism of fungal
      bioluminescence, and describe the use of simple synthetic alpha-pyrones as
      luciferins to produce multicolor enzymatic chemiluminescence. A high-energy
      endoperoxide is proposed as an intermediate of the oxidation of the native
      luciferin to the oxyluciferin, which is a pyruvic acid adduct of caffeic acid.
      Luciferase promiscuity allows the use of simple alpha-pyrones as chemiluminescent
      substrates.

PMID- 28508052
TI  - Miocene flooding events of western Amazonia.
AB  - There is a considerable controversy about whether western Amazonia was ever
      covered by marine waters during the Miocene [23 to 5 Ma (million years ago)]. We
      investigated the possible occurrence of Miocene marine incursions in the Llanos
      and Amazonas/Solimoes basins, using sedimentological and palynological data from
      two sediment cores taken in eastern Colombia and northwestern Brazil together
      with seismic information. We observed two distinct marine intervals in the Llanos
      Basin, an early Miocene that lasted ~0.9 My (million years) (18.1 to 17.2 Ma) and
      a middle Miocene that lasted ~3.7 My (16.1 to 12.4 Ma). These two marine
      intervals are also seen in Amazonas/Solimoes Basin (northwestern Amazonia) but
      were much shorter in duration, ~0.2 My (18.0 to 17.8 Ma) and ~0.4 My (14.1 to
      13.7 Ma), respectively. Our results indicate that shallow marine waters covered
      the region at least twice during the Miocene, but the events were short-lived,
      rather than a continuous full-marine occupancy of Amazonian landscape over
      millions of years.

PMID- 28508050
TI  - Butterfly gyroid nanostructures as a time-frozen glimpse of intracellular
      membrane development.
AB  - The formation of the biophotonic gyroid material in butterfly wing scales is an
      exceptional feat of evolutionary engineering of functional nanostructures. It is
      hypothesized that this nanostructure forms by chitin polymerization inside a
      convoluted membrane of corresponding shape in the endoplasmic reticulum. However,
      this dynamic formation process, including whether membrane folding and chitin
      expression are simultaneous or sequential processes, cannot yet be elucidated by
      in vivo imaging. We report an unusual hierarchical ultrastructure in the
      butterfly Thecla opisena that, as a solid material, allows high-resolution three
      dimensional microscopy. Rather than the conventional polycrystalline space
      filling arrangement, a gyroid occurs in isolated facetted crystallites with a
      pronounced size gradient. When interpreted as a sequence of time-frozen snapshots
      of the morphogenesis, this arrangement provides insight into the formation
      mechanisms of the nanoporous gyroid material as well as of the intracellular
      organelle membrane that acts as the template.

PMID- 28508053
TI  - Backside absorbing layer microscopy: Watching graphene chemistry.
AB  - The rapid rise of two-dimensional nanomaterials implies the development of new
      versatile, high-resolution visualization and placement techniques. For example, a
      single graphene layer becomes observable on Si/SiO2 substrates by reflected light
      under optical microscopy because of interference effects when the thickness of
      silicon oxide is optimized. However, differentiating monolayers from bilayers
      remains challenging, and advanced techniques, such as Raman mapping, atomic force
      microscopy (AFM), or scanning electron microscopy (SEM) are more suitable to
      observe graphene monolayers. The first two techniques are slow, and the third is
      operated in vacuum; hence, in all cases, real-time experiments including notably
      chemical modifications are not accessible. The development of optical microscopy
      techniques that combine the speed, large area, and high contrast of SEM with the
      topological information of AFM is therefore highly desirable. We introduce a new
      widefield optical microscopy technique based on the use of previously unknown
      antireflection and absorbing (ARA) layers that yield ultrahigh contrast
      reflection imaging of monolayers. The BALM (backside absorbing layer microscopy)
      technique can achieve the subnanometer-scale vertical resolution, large area, and
      real-time imaging. Moreover, the inverted optical microscope geometry allows its
      easy implementation and combination with other techniques. We notably demonstrate
      the potentiality of BALM by in operando imaging chemical modifications of
      graphene oxide. The technique can be applied to the deposition, observation, and
      modification of any nanometer-thick materials.

PMID- 28508051
TI  - Genuine binding energy of the hydrated electron.
AB  - The unknown influence of inelastic and elastic scattering of slow electrons in
      water has made it difficult to clarify the role of the solvated electron in
      radiation chemistry and biology. We combine accurate scattering simulations with
      experimental photoemission spectroscopy of the hydrated electron in a liquid
      water microjet, with the aim of resolving ambiguities regarding the influence of
      electron scattering on binding energy spectra, photoelectron angular
      distributions, and probing depths. The scattering parameters used in the
      simulations are retrieved from independent photoemission experiments of water
      droplets. For the ground-state hydrated electron, we report genuine values devoid
      of scattering contributions for the vertical binding energy and the anisotropy
      parameter of 3.7 +/- 0.1 eV and 0.6 +/- 0.2, respectively. Our probing depths
      suggest that even vacuum ultraviolet probing is not particularly surface
      selective. Our work demonstrates the importance of quantitative scattering
      simulations for a detailed analysis of key properties of the hydrated electron.

PMID- 28508054
TI  - Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia
      osimensis.
AB  - In mammals, the Y chromosome strictly influences the maintenance of male germ
      cells. Almost all mammalian species require genetic contributors to generate
      testes. An endangered species, Tokudaia osimensis, has a unique sex chromosome
      composition XO/XO, and genetic differences between males and females have not
      been confirmed. Although a distinctive sex-determining mechanism may exist in T.
      osimensis, it has been difficult to examine thoroughly in this rare animal
      species. To elucidate the discriminative sex-determining mechanism in T.
      osimensis and to find a strategy to prevent its possible extinction, we have
      established induced pluripotent stem cells (iPSCs) and derived interspecific
      chimeras using mice as the hosts and recipients. Generated iPSCs are considered
      to be in the so-called "true naive" state, and T. osimensis iPSCs may contribute
      as interspecific chimeras to several different tissues and cells in live animals.
      Surprisingly, female T. osimensis iPSCs not only contributed to the female germ
      line in the interspecific mouse ovary but also differentiated into spermatocytes
      and spermatids that survived in the adult interspecific mouse testes. Thus, T.
      osimensis cells have high sexual plasticity through which female somatic cells
      can be converted to male germline cells. These findings suggest flexibility in T.
      osimensis cells, which can adapt their germ cell sex to the gonadal niche. The
      probable reduction of the extinction risk of an endangered species through the
      use of iPSCs is indicated by this study.

PMID- 28508056
TI  - Picosecond amorphization of SiO2 stishovite under tension.
AB  - It is extremely difficult to realize two conflicting properties-high hardness and
      toughness-in one material. Nano-polycrystalline stishovite, recently synthesized
      from Earth-abundant silica glass, proved to be a super-hard, ultra-tough
      material, which could provide sustainable supply of high-performance ceramics.
      Our quantum molecular dynamics simulations show that stishovite amorphizes
      rapidly on the order of picosecond under tension in front of a crack tip. We find
      a displacive amorphization mechanism that only involves short-distance collective
      motions of atoms, thereby facilitating the rapid transformation. The two-step
      amorphization pathway involves an intermediate state akin to experimentally
      suggested "high-density glass polymorphs" before eventually transforming to
      normal glass. The rapid amorphization can catch up with, screen, and self-heal a
      fast-moving crack. This new concept of fast amorphization toughening likely
      operates in other pressure-synthesized hard solids.

PMID- 28508057
TI  - Low-energy structural dynamics of ferroelectric domain walls in hexagonal rare
      earth manganites.
AB  - Domain walls (DWs) in ferroic materials, across which the order parameter
      abruptly changes its orientation, can host emergent properties that are absent in
      the bulk domains. Using a broadband (106 to 1010 Hz) scanning impedance
      microscope, we show that the electrical response of the interlocked antiphase
      boundaries and ferroelectric DWs in hexagonal rare-earth manganites (h-RMnO3) is
      dominated by the bound-charge oscillation rather than free-carrier conduction at
      the DWs. As a measure of the rate of energy dissipation, the effective
      conductivity of DWs on the (001) surfaces of h-RMnO3 at gigahertz frequencies is
      drastically higher than that at dc, whereas the effect is absent on surfaces with
      in-plane polarized domains. First-principles and model calculations indicate that
      the frequency range and selection rules are consistent with the periodic sliding
      of the DW around its equilibrium position. This acoustic wave-like mode, which is
      associated with the synchronized oscillation of local polarization and apical
      oxygen atoms, is localized perpendicular to the DW but free to propagate along
      the DW plane. Our results break the ground to understand structural DW dynamics
      and exploit new interfacial phenomena for novel devices.

PMID- 28508058
TI  - New technology reveals the role of giant larvaceans in oceanic carbon cycling.
AB  - To accurately assess the impacts of climate change on our planet, modeling of
      oceanic systems and understanding how atmospheric carbon is transported from
      surface waters to the deep benthos are required. The biological pump drives the
      transport of carbon through the ocean's depths, and the rates at which carbon is
      removed and sequestered are often dependent on the grazing abilities of surface
      and midwater organisms. Some of the most effective and abundant midwater grazers
      are filter-feeding invertebrates. Although the impact of smaller, near-surface
      filter feeders is generally known, efforts to quantify the impact of deeper
      filter feeders, such as giant larvaceans, have been unsuccessful. Giant
      larvaceans occupy the upper 400 m of the water column, where they build complex
      mucus filtering structures that reach diameters greater than 1 m. Because of the
      fragility of these structures, direct measurements of filtration rates require in
      situ methods. Hence, we developed DeepPIV, an instrument deployed from a remotely
      operated vehicle that enables the direct measurement of in situ filtration rates.
      The rates measured for giant larvaceans exceed those of any other zooplankton
      filter feeder. Given these filtration rates and abundance data from a 22-year
      time series, the grazing impact of giant larvaceans far exceeds previous
      estimates, with the potential for processing their 200-m principal depth range in
      Monterey Bay in as little as 13 days. Technologies such as DeepPIV will enable
      more accurate assessments of the long-term removal of atmospheric carbon by deep
      water biota.

PMID- 28508055
TI  - Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K+
      channels in parkinsonian discharges.
AB  - ERG K+ channels have long been known to play a crucial role in shaping cardiac
      action potentials and, thus, appropriate heart rhythms. The functional role of
      ERG channels in the central nervous system, however, remains elusive. We
      demonstrated that ERG channels exist in subthalamic neurons and have similar
      gating characteristics to those in the heart. ERG channels contribute crucially
      not only to the setting of membrane potential and, consequently, the firing
      modes, but also to the configuration of burst discharges and, consequently, the
      firing frequency and automaticity of the subthalamic neurons. Moreover,
      modulation of subthalamic discharges via ERG channels effectively modulates
      locomotor behaviors. ERG channel inhibitors ameliorate parkinsonian symptoms,
      whereas enhancers render normal animals hypokinetic. Thus, ERG K+ channels could
      be vital to the regulation of both cardiac and neuronal rhythms and may
      constitute an important pathophysiological basis and pharmacotherapeutic target
      for the growing list of neurological disorders related to "brain arrhythmias."

PMID- 28508059
TI  - Experimental evidence of hourglass fermion in the candidate nonsymmorphic
      topological insulator KHgSb.
AB  - Topological insulators (TIs) host novel states of quantum matter characterized by
      nontrivial conducting boundary states connecting valence and conduction bulk
      bands. All TIs discovered experimentally so far rely on either time-reversal or
      mirror crystal symmorphic symmetry to protect massless Dirac-like boundary
      states. Several materials were recently proposed to be TIs with nonsymmorphic
      symmetry, where a glide mirror protects exotic surface fermions with hourglass
      shaped dispersion. However, an experimental confirmation of this new fermion is
      missing. Using angle-resolved photoemission spectroscopy, we provide experimental
      evidence of hourglass fermions on the (010) surface of crystalline KHgSb, whereas
      the (001) surface has no boundary state, in agreement with first-principles
      calculations. Our study will stimulate further research activities of topological
      properties of nonsymmorphic materials.

PMID- 28508061
TI  - Electroplating lithium transition metal oxides.
AB  - Materials synthesis often provides opportunities for innovation. We demonstrate a
      general low-temperature (260 degrees C) molten salt electrodeposition approach to
      directly electroplate the important lithium-ion (Li-ion) battery cathode
      materials LiCoO2, LiMn2O4, and Al-doped LiCoO2. The crystallinities and
      electrochemical capacities of the electroplated oxides are comparable to those of
      the powders synthesized at much higher temperatures (700 degrees  to 1000 degrees
      C). This new growth method significantly broadens the scope of battery form
      factors and functionalities, enabling a variety of highly desirable battery
      properties, including high energy, high power, and unprecedented electrode
      flexibility.

PMID- 28508060
TI  - In vivo mapping of tissue- and subcellular-specific proteomes in Caenorhabditis
      elegans.
AB  - Multicellular organisms are composed of tissues that have distinct functions
      requiring specialized proteomes. To define the proteome of a live animal with
      tissue and subcellular resolution, we adapted a localized proteomics technology
      for use in the multicellular model organism Caenorhabditis elegans. This approach
      couples tissue- and location-specific expression of the enzyme ascorbate
      peroxidase (APX), which enables proximity-based protein labeling in vivo, and
      quantitative proteomics to identify tissue- and subcellular-restricted proteomes.
      We identified and localized more than 3000 proteins from strains of C. elegans
      expressing APX in either the nucleus or cytoplasm of the intestine, epidermis,
      body wall muscle, or pharyngeal muscle. We also identified several hundred
      proteins that were specifically localized to one of the four tissues analyzed or
      specifically localized to the cytoplasm or the nucleus. This approach resulted in
      the identification both of proteins with previously characterized localizations
      and of those not known to localize to the nucleus or cytoplasm. Further, we
      confirmed the tissue- and subcellular-specific localization of a subset of
      identified proteins using green fluorescent protein tagging and fluorescence
      microscopy, validating our in vivo proximity-based proteomics technique.
      Together, these results demonstrate a new approach that enables the tissue- and
      subcellular-specific identification and quantification of proteins within a live
      animal.

PMID- 28508062
TI  - Resonant laser printing of structural colors on high-index dielectric
      metasurfaces.
AB  - Man-made structural colors, which originate from resonant interactions between
      visible light and manufactured nanostructures, are emerging as a solution for ink
      free color printing. We show that non-iridescent structural colors can be
      conveniently produced by nanostructures made from high-index dielectric
      materials. Compared to plasmonic analogs, color surfaces with high-index
      dielectrics, such as germanium (Ge), have a lower reflectance, yielding a
      superior color contrast. Taking advantage of band-to-band absorption in Ge, we
      laser-postprocess Ge color metasurfaces with morphology-dependent resonances.
      Strong on-resonance energy absorption under pulsed laser irradiation locally
      elevates the lattice temperature (exceeding 1200 K) in an ultrashort time scale
      (1 ns). This forms the basis for resonant laser printing, where rapid melting
      allows for surface energy-driven morphology changes with associated modification
      of color appearance. Laser-printable high-index dielectric color metasurfaces are
      scalable to a large area and open a new paradigm for printing and decoration with
      nonfading and vibrant colors.

PMID- 28508065
TI  - The ground truth about metadata and community detection in networks.
AB  - Across many scientific domains, there is a common need to automatically extract a
      simplified view or coarse-graining of how a complex system's components interact.
      This general task is called community detection in networks and is analogous to
      searching for clusters in independent vector data. It is common to evaluate the
      performance of community detection algorithms by their ability to find so-called
      ground truth communities. This works well in synthetic networks with planted
      communities because these networks' links are formed explicitly based on those
      known communities. However, there are no planted communities in real-world
      networks. Instead, it is standard practice to treat some observed discrete-valued
      node attributes, or metadata, as ground truth. We show that metadata are not the
      same as ground truth and that treating them as such induces severe theoretical
      and practical problems. We prove that no algorithm can uniquely solve community
      detection, and we prove a general No Free Lunch theorem for community detection,
      which implies that there can be no algorithm that is optimal for all possible
      community detection tasks. However, community detection remains a powerful tool
      and node metadata still have value, so a careful exploration of their
      relationship with network structure can yield insights of genuine worth. We
      illustrate this point by introducing two statistical techniques that can quantify
      the relationship between metadata and community structure for a broad class of
      models. We demonstrate these techniques using both synthetic and real-world
      networks, and for multiple types of metadata and community structures.

PMID- 28508063
TI  - The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre
      mRNA molecules.
AB  - Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence
      cancerous condition are poorly understood. The aberrant expression of SPRIGHTLY
      lncRNA, encoded within the drosophila gene homolog Sprouty-4 intron, is
      correlated with a variety of cancers, including human melanomas. We demonstrate
      by SHAPE-seq and dChIRP that SPRIGHTLY RNA secondary structure has a core
      pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre
      mRNAs: SOX5, SMYD3, SND1, MEOX2, DCTN6, and RASAL2, all of which have cancer
      related functions. Hemizygous knockout of SPRIGHTLY by CRISPR (clustered
      regularly interspaced short palindromic repeats)/Cas9 in melanoma cells
      significantly decreases SPRIGHTLY lncRNA levels, simultaneously decreases the
      levels of its interacting pre-mRNA molecules, and decreases anchorage-independent
      growth rate of cells and the rate of in vivo tumor growth in mouse xenografts.
      These results provide the first demonstration of an lncRNA's three-dimensional
      coordinating role in facilitating cancer-related gene expression in human
      melanomas.

PMID- 28508066
TI  - Australian shelf sediments reveal shifts in Miocene Southern Hemisphere
      westerlies.
AB  - Global climate underwent a major reorganization when the Antarctic ice sheet
      expanded ~14 million years ago (Ma) (1). This event affected global atmospheric
      circulation, including the strength and position of the westerlies and the
      Intertropical Convergence Zone (ITCZ), and, therefore, precipitation patterns (2
      5). We present new shallow-marine sediment records from the continental shelf of
      Australia (International Ocean Discovery Program Sites U1459 and U1464) providing
      the first empirical evidence linking high-latitude cooling around Antarctica to
      climate change in the (sub)tropics during the Miocene. We show that Western
      Australia was arid during most of the Middle Miocene. Southwest Australia became
      wetter during the Late Miocene, creating a climate gradient with the arid
      interior, whereas northwest Australia remained arid throughout. Precipitation and
      river runoff in southwest Australia gradually increased from 12 to 8 Ma, which we
      relate to a northward migration or intensification of the westerlies possibly due
      to increased sea ice in the Southern Ocean (5). Abrupt aridification indicates
      that the westerlies shifted back to a position south of Australia after 8 Ma. Our
      midlatitude Southern Hemisphere data are consistent with the inference that
      expansion of sea ice around Antarctica resulted in a northward movement of the
      westerlies. In turn, this may have pushed tropical atmospheric circulation and
      the ITCZ northward, shifting the main precipitation belt over large parts of
      Southeast Asia (4).

PMID- 28508064
TI  - Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not
      muscular arteries.
AB  - Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to
      autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder
      characterized by significant cardiovascular abnormalities, including abnormal
      elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to
      determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on
      the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B.
      Fbln4E57K/E57K mice were hypertensive and developed arterial elongation,
      tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization
      within the arterial wall of large conducting vessels was abnormal, and elastic
      fibers were fragmented and had a moth-eaten appearance. In contrast, vessel wall
      structure and elastic fiber integrity were normal in resistance/muscular arteries
      (renal, mesenteric, and saphenous). Elastin cross-linking and total elastin
      content were unchanged in large or small arteries, whereas elastic fiber
      architecture was abnormal in large vessels. While the E57K mutation did not
      affect Fbln4 mRNA levels, FBLN4 protein was lower in the ascending aorta of
      mutant animals compared to wild-type arteries but equivalent in mesenteric
      arteries. We found a differential role of FBLN4 in elastic fiber assembly, where
      it functions mainly in large conduit arteries. These results suggest that elastin
      assembly has different requirements depending on vessel type. Normal levels of
      elastin cross-links in mutant tissue call into question FBLN4's suggested role in
      mediating lysyl oxidase-elastin interactions. Future studies investigating tissue
      specific elastic fiber assembly may lead to novel therapeutic interventions for
      ARCL1B and other disorders of elastic fiber assembly.

PMID- 28508068
TI  - Emergence of topological semimetals in gap closing in semiconductors without
      inversion symmetry.
AB  - A band gap for electronic states in crystals governs various properties of
      solids, such as transport, optical, and magnetic properties. Its estimation and
      control have been an important issue in solid-state physics. The band gap can be
      controlled externally by various parameters, such as pressure, atomic
      compositions, and external field. Sometimes, the gap even collapses by tuning
      some parameter. In the field of topological insulators, this closing of the gap
      at a time-reversal invariant momentum indicates a band inversion, that is, it
      leads to a topological phase transition from a normal insulator to a topological
      insulator. We show, through an exhaustive study on possible space groups, that
      the gap closing in inversion-asymmetric crystals is universal, in the sense that
      the gap closing always leads either to a Weyl semimetal or to a nodal-line
      semimetal. We consider three-dimensional spinful systems with time-reversal
      symmetry. The space group of the system and the wave vector at the gap closing
      uniquely determine which possibility occurs and where the gap-closing points or
      lines lie in the wave vector space after the closing of the gap. In particular,
      we show that an insulator-to-insulator transition never happens, which is in
      sharp contrast to inversion-symmetric systems.

PMID- 28508067
TI  - Cryo-EM structure of human adenovirus D26 reveals the conservation of structural
      organization among human adenoviruses.
AB  - Human adenoviruses (HAdVs) cause acute respiratory, ocular, and gastroenteric
      diseases and are also frequently used as gene and vaccine delivery vectors.
      Unlike the archetype human adenovirus C5 (HAdV-C5), human adenovirus D26 (HAdV
      D26) belongs to species-D HAdVs, which target different cellular receptors, and
      is differentially recognized by immune surveillance mechanisms. HAdV-D26 is being
      championed as a lower seroprevalent vaccine and oncolytic vector in preclinical
      and human clinical studies. To understand the molecular basis for their distinct
      biological properties and independently validate the structures of minor
      proteins, we determined the first structure of species-D HAdV at 3.7 A resolution
      by cryo-electron microscopy. All the hexon hypervariable regions (HVRs),
      including HVR1, have been identified and exhibit a distinct organization compared
      to those of HAdV-C5. Despite the differences in the arrangement of helices in the
      coiled-coil structures, protein IX molecules form a continuous hexagonal network
      on the capsid exterior. In addition to the structurally conserved region (3 to
      300) of IIIa, we identified an extra helical domain comprising residues 314 to
      390 that further stabilizes the vertex region. Multiple (two to three) copies of
      the cleaved amino-terminal fragment of protein VI (pVIn) are observed in each
      hexon cavity, suggesting that there could be >=480 copies of VI present in HAdV
      D26. In addition, a localized asymmetric reconstruction of the vertex region
      provides new details of the three-pronged "claw hold" of the trimeric fiber and
      its interactions with the penton base. These observations resolve the previous
      conflicting assignments of the minor proteins and suggest the likely conservation
      of their organization across different HAdVs.

PMID- 28508069
TI  - High-predation habitats affect the social dynamics of collective exploration in a
      shoaling fish.
AB  - Collective decisions play a major role in the benefits that animals gain from
      living in groups. Although the mechanisms of how groups collectively make
      decisions have been extensively researched, the response of within-group dynamics
      to ecological conditions is virtually unknown, despite adaptation to the
      environment being a cornerstone in biology. We investigate how within-group
      interactions during exploration of a novel environment are shaped by predation, a
      major influence on the behavior of prey species. We tested guppies (Poecilia
      reticulata) from rivers varying in predation risk under controlled laboratory
      conditions and find the first evidence of differences in group interactions
      between animals adapted to different levels of predation. Fish from high
      predation habitats showed the strongest negative relationship between initiating
      movements and following others, which resulted in less variability in the total
      number of movements made between individuals. This relationship between
      initiating movements and following others was associated with differentiation
      into initiators and followers, which was only observed in fish from high
      predation rivers. The differentiation occurred rapidly, as trials lasted 5 min,
      and was related to shoal cohesion, where more diverse groups from high-predation
      habitats were more cohesive. Our results show that even within a single species
      over a small geographical range, decision-making in a social context can vary
      with local ecological factors.

PMID- 28508071
TI  - Self-assembled micro-organogels for 3D printing silicone structures.
AB  - The widespread prevalence of commercial products made from microgels illustrates
      the immense practical value of harnessing the jamming transition; there are
      countless ways to use soft, solid materials that fluidize and become solid again
      with small variations in applied stress. The traditional routes of microgel
      synthesis produce materials that predominantly swell in aqueous solvents or, less
      often, in aggressive organic solvents, constraining ways that these exceptionally
      useful materials can be used. For example, aqueous microgels have been used as
      the foundation of three-dimensional (3D) bioprinting applications, yet the
      incompatibility of available microgels with nonpolar liquids, such as oils,
      limits their use in 3D printing with oil-based materials, such as silicone. We
      present a method to make micro-organogels swollen in mineral oil, using block
      copolymer self-assembly. The rheological properties of this micro-organogel
      material can be tuned, leveraging the jamming transition to facilitate its use in
      3D printing of silicone structures. We find that the minimum printed feature size
      can be controlled by the yield stress of the micro-organogel medium, enabling the
      fabrication of numerous complex silicone structures, including branched
      perfusable networks and functional fluid pumps.

PMID- 28508070
TI  - Decoupling of microbial carbon, nitrogen, and phosphorus cycling in response to
      extreme temperature events.
AB  - Predicted changes in the intensity and frequency of climate extremes urge a
      better mechanistic understanding of the stress response of microbially mediated
      carbon (C) and nutrient cycling processes. We analyzed the resistance and
      resilience of microbial C, nitrogen (N), and phosphorus (P) cycling processes and
      microbial community composition in decomposing plant litter to transient, but
      severe, temperature disturbances, namely, freeze-thaw and heat. Disturbances led
      temporarily to a more rapid cycling of C and N but caused a down-regulation of P
      cycling. In contrast to the fast recovery of the initially stimulated C and N
      processes, we found a slow recovery of P mineralization rates, which was not
      accompanied by significant changes in community composition. The functional and
      structural responses to the two distinct temperature disturbances were markedly
      similar, suggesting that direct negative physical effects and costs associated
      with the stress response were comparable. Moreover, the stress response of
      extracellular enzyme activities, but not that of intracellular microbial
      processes (for example, respiration or N mineralization), was dependent on the
      nutrient content of the resource through its effect on microbial physiology and
      community composition. Our laboratory study provides novel insights into the
      mechanisms of microbial functional stress responses that can serve as a basis for
      field studies and, in particular, illustrates the need for a closer integration
      of microbial C-N-P interactions into climate extremes research.

PMID- 28508072
TI  - Dramatic influence of curvature of nanowire on chiral domain wall velocity.
AB  - The use of current pulses to move domain walls along nanowires is one of the most
      exciting developments in spintronics over the past decade. We show that changing
      the sign of the curvature of a nanowire changes the speed of chiral Neel domain
      walls in perpendicularly magnetized nanowires by up to a factor of 10. The domain
      walls have an increased or decreased velocity in wires of a given curvature,
      independent of the domain wall chirality and the sign of the current-induced spin
      orbit torques. Thus, adjacent domain walls move at different speeds. For steady
      motion of domain walls along the curved nanowire, the torque must increase
      linearly with the radius, which thereby results in a width-dependent tilting of
      the domain wall. We show that by using synthetic antiferromagnetic nanowires, the
      influence of the curvature on the domain wall's velocity is eliminated, and all
      domain walls move together, emphasizing the use of such structures for spintronic
      applications.

PMID- 28508073
TI  - Three-dimensional system enabling the maintenance and directed differentiation of
      pluripotent stem cells under defined conditions.
AB  - The development of in vitro models for the maintenance and differentiation of
      pluripotent stem cells (PSCs) is an active area of stem cell research. The
      strategies used so far are based mainly on two-dimensional (2D) cultures, in
      which cellular phenotypes are regulated by soluble factors. We show that a 3D
      culture system with atelocollagen porous scaffolds can significantly improve the
      outcome of the current platforms intended for the maintenance and lineage
      specification of mouse PSCs (mPSCs). Unlike 2D conditions, the 3D conditions
      maintained the undifferentiated state of mouse embryonic stem cells (mESCs)
      without exogenous stimulation and also supported endoderm, mesoderm, and ectoderm
      differentiation of mESCs under serum-free conditions. Moreover, 3D mPSC-derived
      mesodermal cells showed accelerated osteogenic differentiation, giving rise to
      functional osteoblast-osteocyte populations within calcified structures. The
      present strategy offers a 3D platform suitable for the formation of organoids
      that mimic in vivo organs containing various cell types, and it may be adaptable
      to the generation of ectoderm-, mesoderm-, and endoderm-derived tissues when
      combined with appropriate differentiation treatments.

PMID- 28508074
TI  - Pressure compression of CdSe nanoparticles into luminescent nanowires.
AB  - Oriented attachment (OA) of synthetic nanocrystals is emerging as an effective
      means of fabricating low-dimensional nanoscale materials. However, OA relies on
      energetically favorable nanocrystal facets to grow nanostructured materials.
      Consequently, nanostructures synthesized through OA are generally limited to a
      specific crystal facet in their final morphology. We report our discovery that
      high-pressure compression can induce consolidation of spherical CdSe nanocrystal
      arrays, leading to unexpected one-dimensional semiconductor nanowires that do not
      exhibit the typical crystal facet. In particular, in situ high-pressure
      synchrotron x-ray scattering, optical spectroscopy, and high-resolution
      transmission electron microscopy characterizations indicate that by manipulating
      the coupling between nanocrystals through external pressure, a reversible change
      in nanocrystal assemblies and properties can be achieved at modest pressure. When
      pressure is increased above a threshold, these nanocrystals begin to contact one
      another and consolidate, irreversibly forming one-dimensional luminescent
      nanowires. High-fidelity molecular dynamics (MD) methods were used to calculate
      surface energies and simulate compression and coalescence mechanisms of CdSe
      nanocrystals. The MD results provide new insight into nanowire assembly dynamics
      and phase stability of nanocrystalline structures.

PMID- 28508076
TI  - Machine learning of accurate energy-conserving molecular force fields.
AB  - Using conservation of energy-a fundamental property of closed classical and
      quantum mechanical systems-we develop an efficient gradient-domain machine
      learning (GDML) approach to construct accurate molecular force fields using a
      restricted number of samples from ab initio molecular dynamics (AIMD)
      trajectories. The GDML implementation is able to reproduce global potential
      energy surfaces of intermediate-sized molecules with an accuracy of 0.3 kcal mol
      1 for energies and 1 kcal mol-1 A-1 for atomic forces using only 1000
      conformational geometries for training. We demonstrate this accuracy for AIMD
      trajectories of molecules, including benzene, toluene, naphthalene, ethanol,
      uracil, and aspirin. The challenge of constructing conservative force fields is
      accomplished in our work by learning in a Hilbert space of vector-valued
      functions that obey the law of energy conservation. The GDML approach enables
      quantitative molecular dynamics simulations for molecules at a fraction of cost
      of explicit AIMD calculations, thereby allowing the construction of efficient
      force fields with the accuracy and transferability of high-level ab initio
      methods.

PMID- 28508075
TI  - Fast iodide-SAD phasing for high-throughput membrane protein structure
      determination.
AB  - We describe a fast, easy, and potentially universal method for the de novo
      solution of the crystal structures of membrane proteins via iodide-single
      wavelength anomalous diffraction (I-SAD). The potential universality of the
      method is based on a common feature of membrane proteins-the availability at the
      hydrophobic-hydrophilic interface of positively charged amino acid residues with
      which iodide strongly interacts. We demonstrate the solution using I-SAD of four
      crystal structures representing different classes of membrane proteins, including
      a human G protein-coupled receptor (GPCR), and we show that I-SAD can be applied
      using data collection strategies based on either standard or serial x-ray
      crystallography techniques.

PMID- 28508077
TI  - Resilience offers escape from trapped thinking on poverty alleviation.
AB  - The poverty trap concept strongly influences current research and policy on
      poverty alleviation. Financial or technological inputs intended to "push" the
      rural poor out of a poverty trap have had many successes but have also failed
      unexpectedly with serious ecological and social consequences that can reinforce
      poverty. Resilience thinking can help to (i) understand how these failures emerge
      from the complex relationships between humans and the ecosystems on which they
      depend and (ii) navigate diverse poverty alleviation strategies, such as
      transformative change, that may instead be required. First, we review commonly
      observed or assumed social-ecological relationships in rural development
      contexts, focusing on economic, biophysical, and cultural aspects of poverty.
      Second, we develop a classification of poverty alleviation strategies using
      insights from resilience research on social-ecological change. Last, we use these
      advances to develop stylized, multidimensional poverty trap models. The models
      show that (i) interventions that ignore nature and culture can reinforce poverty
      (particularly in agrobiodiverse landscapes), (ii) transformative change can
      instead open new pathways for poverty alleviation, and (iii) asset inputs may be
      effective in other contexts (for example, where resource degradation and poverty
      are tightly interlinked). Our model-based approach and insights offer a
      systematic way to review the consequences of the causal mechanisms that
      characterize poverty traps in different agricultural contexts and identify
      appropriate strategies for rural development challenges.

PMID- 28508078
TI  - The exceptional sediment load of fine-grained dispersal systems: Example of the
      Yellow River, China.
AB  - Sedimentary dispersal systems with fine-grained beds are common, yet the physics
      of sediment movement within them remains poorly constrained. We analyze sediment
      transport data for the best-documented, fine-grained river worldwide, the Huanghe
      (Yellow River) of China, where sediment flux is underpredicted by an order of
      magnitude according to well-accepted sediment transport relations. Our
      theoretical framework, bolstered by field observations, demonstrates that the
      Huanghe tends toward upper-stage plane bed, yielding minimal form drag, thus
      markedly enhancing sediment transport efficiency. We present a sediment transport
      formulation applicable to all river systems with silt to coarse-sand beds. This
      formulation demonstrates a remarkably sensitive dependence on grain size within a
      certain narrow range and therefore has special relevance to silt-sand fluvial
      systems, particularly those affected by dams.

PMID- 28508079
TI  - A twofold quantum delayed-choice experiment in a superconducting circuit.
AB  - Wave-particle complementarity lies at the heart of quantum mechanics. To
      illustrate this mysterious feature, Wheeler proposed the delayed-choice
      experiment, where a quantum system manifests the wave- or particle-like
      attribute, depending on the experimental arrangement, which is made after the
      system has entered the interferometer. In recent quantum delayed-choice
      experiments, these two complementary behaviors were simultaneously observed with
      a quantum interferometer in a superposition of being closed and open. We suggest
      and implement a conceptually different quantum delayed-choice experiment by
      introducing a which-path detector (WPD) that can simultaneously record and
      neglect the system's path information, but where the interferometer itself is
      classical. Our experiment is realized with a superconducting circuit, where a
      cavity acts as the WPD for an interfering qubit. Using this setup, we implement
      the first twofold delayed-choice experiment, which demonstrates that the system's
      behavior depends not only on the measuring device's configuration that can be
      chosen even after the system has been detected but also on whether we a
      posteriori erase or mark the which-path information, the latter of which cannot
      be revealed by previous quantum delayed-choice experiments. Our results represent
      the first demonstration of both counterintuitive features with the same
      experimental setup, significantly extending the concept of quantum delayed-choice
      experiment.

PMID- 28508080
TI  - Direct quantitative measurement of the C?O???H-C bond by atomic force microscopy.
AB  - The hydrogen atom-the smallest and most abundant atom-is of utmost importance in
      physics and chemistry. Although many analysis methods have been applied to its
      study, direct observation of hydrogen atoms in a single molecule remains largely
      unexplored. We use atomic force microscopy (AFM) to resolve the outermost
      hydrogen atoms of propellane molecules via very weak C?O???H-C hydrogen bonding
      just before the onset of Pauli repulsion. The direct measurement of the
      interaction with a hydrogen atom paves the way for the identification of three
      dimensional molecules such as DNAs and polymers, building the capabilities of AFM
      toward quantitative probing of local chemical reactivity.

PMID- 28508081
TI  - Evidence and mechanism of efficient thermally activated delayed fluorescence
      promoted by delocalized excited states.
AB  - The design of organic compounds with nearly no gap between the first excited
      singlet (S1) and triplet (T1) states has been demonstrated to result in an
      efficient spin-flip transition from the T1 to S1 state, that is, reverse
      intersystem crossing (RISC), and facilitate light emission as thermally activated
      delayed fluorescence (TADF). However, many TADF molecules have shown that a
      relatively appreciable energy difference between the S1 and T1 states (~0.2 eV)
      could also result in a high RISC rate. We revealed from a comprehensive study of
      optical properties of TADF molecules that the formation of delocalized states is
      the key to efficient RISC and identified a chemical template for these materials.
      In addition, simple structural confinement further enhances RISC by suppressing
      structural relaxation in the triplet states. Our findings aid in designing
      advanced organic molecules with a high rate of RISC and, thus, achieving the
      maximum theoretical electroluminescence efficiency in organic light-emitting
      diodes.

PMID- 28508082
TI  - A chlorine-free protocol for processing germanium.
AB  - Replacing molecular chlorine and hydrochloric acid with less energy- and risk
      intensive reagents would markedly improve the environmental impact of metal
      manufacturing at a time when demand for metals is rapidly increasing. We describe
      a recyclable quinone/catechol redox platform that provides an innovative
      replacement for elemental chlorine and hydrochloric acid in the conversion of
      either germanium metal or germanium dioxide to a germanium tetrachloride
      substitute. Germanium is classified as a "critical" element based on its high
      dispersion in the environment, growing demand, and lack of suitable substitutes.
      Our approach replaces the oxidizing capacity of chlorine with molecular oxygen
      and replaces germanium tetrachloride with an air- and moisture-stable Ge(IV)
      catecholate that is kinetically competent for conversion to high-purity germanes.

PMID- 28508083
TI  - Structures of closed and open conformations of dimeric human ATM.
AB  - ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase-related
      protein kinase (PIKK) best known for its role in DNA damage response. ATM also
      functions in oxidative stress response, insulin signaling, and neurogenesis. Our
      electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic
      equilibrium between closed and open dimers. In the closed state, the PIKK
      regulatory domain blocks the peptide substrate-binding site, suggesting that this
      conformation may represent an inactive or basally active enzyme. The active site
      is held in this closed conformation by interaction with a long helical hairpin in
      the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related
      molecule. The open dimer has two protomers with only a limited contact interface,
      and it lacks the intermolecular interactions that block the peptide-binding site
      in the closed dimer. This suggests that the open conformation may be more active.
      The ATM structure shows the detailed topology of the regulator-interacting N
      terminal helical solenoid. The ATM conformational dynamics shown by the
      structures represent an important step in understanding the enzyme regulation.

PMID- 28508085
TI  - Intragenic DOK7 deletion detected by whole-genome sequencing in congenital
      myasthenic syndromes.
AB  - OBJECTIVE: To identify the genetic cause in a patient affected by ptosis and
      exercise-induced muscle weakness and diagnosed with congenital myasthenic
      syndromes (CMS) using whole-genome sequencing (WGS). METHODS: Candidate gene
      screening and WGS analysis were performed in the case. Allele-specific PCR was
      subsequently performed to confirm the copy number variation (CNV) that was
      suspected from the WGS results. RESULTS: In addition to the previously reported
      frameshift mutation c.1124_1127dup, an intragenic 6,261 bp deletion spanning from
      the 5' untranslated region to intron 2 of the DOK7 gene was identified by WGS in
      the patient with CMS. The heterozygous deletion was suspected based on reduced
      coverage on WGS and confirmed by allele-specific PCR. The breakpoints had
      microhomology and an inverted repeat, which may have led to the development of
      the deletion during DNA replication. CONCLUSIONS: We report a CMS case with
      identification of the breakpoints of the intragenic DOK7 deletion using WGS
      analysis. This case illustrates that CNVs undetected by Sanger sequencing may be
      identified by WGS and highlights their relevance in the molecular diagnosis of a
      treatable neurologic condition such as CMS.

PMID- 28508084
TI  - Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial
      disease.
AB  - OBJECTIVE: Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial
      DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed
      to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients
      with mitochondrial disease and establish clinically meaningful genotype-phenotype
      correlations. METHODS: RNASEH1 was analyzed in patients with (1) multiple
      deletions/depletion of muscle mtDNA and (2) mendelian progressive external
      ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction,
      but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic
      and molecular evaluation of the newly identified and previously reported patients
      harboring RNASEH1 mutations was subsequently undertaken. RESULTS: Pathogenic
      c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74
      probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic
      analysis was undertaken in 50 additional Indian probands with variable clinical
      presentations associated with multiple mtDNA deletions, but no further RNASEH1
      mutations were confirmed. RNASEH1-related mitochondrial disease was characterized
      by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia
      neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A
      p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial
      disease, haplotype analysis suggested an independent origin, rather than a
      founder event, for the variant in our families. CONCLUSIONS: In our cohort,
      RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO
      associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and
      TWNK. RNASEH1 genetic analysis should also be considered in all patients with
      POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by
      which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further
      investigation.

PMID- 28508086
TI  - Revisiting classical design in engineering from a perspective of frugality.
AB  - The conservative nature of design in engineering has typically unleashed products
      fabricated with generous amounts of raw materials. This is epitomized by the
      factor of safety whose values higher than unity suggests various uncertainties of
      design that are tackled through material padding. This effort proposes a new
      factor of safety called the factor of frugality that could be used in ecodesign
      and which addresses both rigors of the classical design process and
      quantification of savings in materials going into a product. An example of frugal
      shaft design together with some other cases has been presented to explain the
      working of the factor of frugality. Adoption of the frugality factor would entail
      a change in design philosophy whereby designers would constantly make avail of a
      rigorous design process coupled with material-saving schemes for realizing
      products that are benign to the environment. Such a change in the foundations of
      design would abet the stewardship of earth in avoiding planetary boundaries since
      engineering influences a significant proportion of human endeavors.

PMID- 28508087
TI  - The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial:
      Rationale and design of a multi-center, double-blind, placebo-controlled trial of
      high dose bolus administration of vitamin D3 during acute pulmonary exacerbation
      of cystic fibrosis.
AB  - Vitamin D deficiency is highly prevalent in children and adults with cystic
      fibrosis (CF). Recent studies have found an association between vitamin D status
      and risk of pulmonary exacerbations in children and adults with CF. The ongoing
      Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a
      multi-center, double-blind, randomized, placebo-controlled trial that will test
      the hypothesis of whether high dose vitamin D given as a single oral bolus of
      250,000 IU to adults with CF during a pulmonary exacerbation followed by a
      maintenance dose of vitamin D will improve time to next pulmonary exacerbation
      and re-hospitalization, improve survival and lung function compared to placebo
      and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1
      at each clinical site to vitamin D or placebo within 72 hours of hospital
      admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1,
      2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum
      will be collected and determination of clinical outcomes will be assessed at each
      visit. The primary endpoint will be the time to next pulmonary exacerbation
      requiring antibiotics, re-hospitalization or death. The secondary endpoints will
      include lung function assessed by forced expiratory volume in 1 second (FEV1),
      blood markers of inflammatory cytokines, anti-microbial peptide expression by
      peripheral blood mononuclear cells and circulating concentrations in blood. Other
      exploratory endpoints will examine the phenotype of neutrophils and
      monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food
      records and food frequency questionnaire.

PMID- 28508089
TI  - Response to Sabour: Dual-energy X-ray absorptiometry and fracture prediction in
      patients with spinal cord injuries and disorders: methodological issues.

PMID- 28508088
TI  - Characterization of the molar mass distribution of macromolecules in beer for
      different mashing processes using asymmetric flow field-flow fractionation (AF4)
      coupled with multiple detectors.
AB  - The macromolecular composition of beer is largely determined by the brewing and
      the mashing process. It is known that the physico-chemical properties of
      proteinaceous and polysaccharide molecules are closely related to the mechanism
      of foam stability. Three types of "American pale ale" style beer were prepared
      using different mashing protocols. The foam stability of the beers was assessed
      using the Derek Rudin standard method. Asymmetric flow field-flow fractionation
      (AF4) in combination with ultraviolet (UV), multiangle light scattering (MALS)
      and differential refractive index (dRI) detectors was used to separate the
      macromolecules present in the beers and the molar mass (M) and molar mass
      distributions (MD) were determined. Macromolecular components were identified by
      enzymatic treatments with beta-glucanase and proteinase K. The MD of beta-glucan
      ranged from 106 to 108 g/mol. In addition, correlation between the beer's
      composition and foam stability was investigated (increased concentration of
      protein and beta-glucan was associated with increased foam stability).

PMID- 28508090
TI  - [Johan Gadolin - namesake for the element gadolinium].

PMID- 28508091
TI  - [MR spectroscopy in metabolic disorders of the brain].
AB  - CLINICAL ISSUE: Metabolic disorders of the brain often present a particular
      challenge for the neuroradiologist, since the disorders are rare, changes on
      conventional MR are often non-specific and there are numerous differential
      diagnoses for the white substance lesions. STANDARD RADIOLOGICAL METHODS: As a
      complementary method to conventional brain MRI, MR spectroscopy may help to
      reduce the scope of the differential diagnosis. Entities with specific MR
      spectroscopy patterns are Canavan disease, maple syrup urine disease, nonketotic
      hyperglycinemia and creatine deficiency.

PMID- 28508092
TI  - A metabonomic analysis on the response of Enterobacter cloacae from coastal
      outfall for land-based pollutant under phoxim stress.
AB  - Enterobacter cloacae is an opportunistic pathogen widely distributed in human and
      animal intestinal systems. The secretion of extended-spectrum beta-lactamases
      (ESBLs) and cephalosporinase (AmpC) endows E. cloacae with strong drug
      resistance. In a previous study by our group, protein expression of E. cloacae
      under phoxim stress was measured by two-dimensional electrophoresis. Here,
      nuclear magnetic resonance was used to detect differences in E. cloacae
      metabonomics when under phoxim stress. We determined that there are 29 types of
      metabolites that differ between phoxim stress and normal culture conditions.
      Among these, 6 types of metabolites were upregulated in the phoxim stress group,
      and 23 types of metabolites were inhibited. Though enrichment analysis, seven
      pathways were identified by different expression levels of metabolites, which
      were involved in DNA and RNA synthesis, DNA damage repair, antioxidation and
      functions of the cell membrane and cell wall. The mechanism underlying how phoxim
      affects E. cloacae was determined by studying the results of both two-dimensional
      electrophoresis in our prior work and the analysis of E. cloacae metabonomic
      changes under phoxim stress.

PMID- 28508093
TI  - Expression of Concern: Modulation of gut microbiota by antibiotics improves
      insulin signalling in high-fat fed mice.

PMID- 28508094
TI  - [Current SHI physician legislation: succession rules for surgical seats :
      Surgical vacancies can be filled with orthopedic/trauma surgery specialists only
      within narrow limits].
AB  - It is a physician's certified continuing medical education category-rather than
      their actual medical activity, in this case in the field of trauma surgery-that
      is decisive in filling statutory health insurance (SHI) practice vacancies. This
      evaluation arising from S16 of the requirement planning guideline applies
      accordingly when filling physician vacancies. Thus physician vacancies or
      statutory health insurance (SHI) practice places can only be filled by a
      physician in the same physician group in line with requirement planning. Scope
      for argumentation initially remains in the context of filling surgical SHI
      physician vacancies where the ceding physician is certified as an accident
      insurance consultant.

PMID- 28508095
TI  - Estimation of glomerular filtration rate in cancer patients with abnormal body
      composition and relation with carboplatin toxicity.
AB  - PURPOSE: Carboplatin clearance is correlated with glomerular filtration rate
      (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG)
      formula. Because plasma creatinine level is highly correlated with muscle mass,
      we hypothesized that an abnormal body composition with a low lean body mass (LBM)
      percentage [(LBM/weight) * 100] may result in inadequate carboplatin dosing.
      Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We
      aimed to investigate the influence of total LBM and LBM percentage on GFR
      calculation, using creatinine (CrCl) or cystatin C (GFRcysC-creat) in cancer
      patients. METHODS: Pretreatment serum creatinine and cystatin C were
      prospectively measured in consecutive patients. CrCl (CG formula), GFRcysC-creat
      (CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe
      thrombocytopenia post-carboplatin were analyzed. RESULTS: In 131 patients without
      renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but
      not with cystatin C (r = -0.07, p = 0.43). In patients with the lowest LBM
      percentage, the CrCl was significantly higher than GFRcysC-creat indicating an
      overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with
      carboplatin AUC 5 (mg/ml min) +/- paclitaxel, the risk of severe thrombocytopenia
      was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFRcysC
      creat ratio (p = 0.006). By ROC analysis, the CrCl/GFRcysC-creat ratio threshold
      predicting severe thrombocytopenia was 1.23. CONCLUSIONS: A low LBM percentage
      increases the risk of inadequate GFR calculation by CG formula, and carboplatin
      overdosage with severe thrombocytopenia. High CrCl/GFRcysC-creat ratio allows the
      identification of these patients.

PMID- 28508096
TI  - [Off-label biologic therapy of ANCA-associated and non-ANCA-associated small
      vessel vasculitis : Efficacy and safety analysis of a national registry
      (GRAID2)].
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of off-label biological
      therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA
      associated small-vessel vasculitis (nAAV) in clinical practice. METHODS: The
      German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective,
      non-interventional, multicentre observational study (August 2006 until December
      2013) on patients with autoimmune diseases refractory to standard
      immunosuppressive therapy treated with off-label biologicals. RESULTS: Data from
      64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%)
      had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA
      associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were
      treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha
      (TNFalpha)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with
      TNFalpha-inhibitors, and 10% with tocilizumab. The main reasons for off-label
      biological treatment in AAV patients were pulmonary, renal, or ear, nose, and
      throat involvement. These manifestations clearly improved in most patients after
      off-label biological therapy was initiated. Daily glucocorticoid dosage could be
      reduced. The off-label biological therapy was generally well tolerated. In AAV
      patients, 4.18 severe infections per 100 patient years were observed. There was
      one death in the nAAV group caused by fungal infection and ileus. A correlation
      between this fatality and RTX treatment was regarded as possible. CONCLUSION:
      Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed
      in the GRAID2 data. Results point to good efficacy and safety of RTX in this
      special patient cohort and support the approval of RTX for AAV induction therapy.

PMID- 28508098
TI  - Patient mortality following alcohol use and trauma: a propensity-matched
      analysis.
AB  - OBJECTIVE: To examine the outcomes of trauma patients who tested positive for
      alcohol at the time of hospital arrival versus those who tested negative.
      METHODS: Data were pulled from the National Trauma Data Bank (2007-2010). All
      injured patients who were >=14 years of age, sustained a "blunt" or "penetrating"
      injury, had complete systolic blood pressure (SBP) and heart rate (HR) records,
      were taken to a level 1 or 2 trauma center, and who received a confirmed blood
      alcohol test were included in the study. Any blood alcohol concentration (BAC)
      above the legal limit (>=0.08 g/dL) was considered "positive" for alcohol, and if
      no alcohol was identified it was considered "negative". Patients' demography and
      clinical information were compared across groups using Chi-square and Wilcoxon
      rank sum tests. Logistic regression, propensity score matching, and a follow-up
      paired analysis were also performed. RESULTS: Of 279,460 total patients, around
      one-third of the patients (92,960) tested positive for BAC. There were clear
      demographic differences found between the two groups regarding age, gender, race,
      and injury type. There was also a significantly higher mortality rate (4.3 vs.
      3.1%, P < 0.001) and a longer hospital length of stay (4 vs. 3 days, P < 0.001)
      found in the alcohol-negative group. Propensity score matching was also performed
      resulting in 92,959 patients per group. Using the paired data, the overall
      mortality observed was 3.1 vs. 3.3% (P = 0.035) between the alcohol-positive and
      alcohol-negative groups, respectively. There was no significant difference noted
      in the total hospital length of stay (median: 3 vs. 4 days, P = 0.84).
      CONCLUSION: Patients who tested positive for alcohol following a traumatic injury
      showed no clinically significant reduction in mortality and no significant
      difference in total hospital length of stay.

PMID- 28508097
TI  - Development of SSR markers and identification of major quantitative trait loci
      controlling shelling percentage in cultivated peanut (Arachis hypogaea L.).
AB  - KEY MESSAGE: A total of 204,439 SSR markers were developed in diploid genomes,
      and 25 QTLs for shelling percentage were identified in a RIL population across 4
      years including five consistent QTLs. Cultivated peanut (Arachis hypogaea L.) is
      an important grain legume providing edible oil and protein for human nutrition.
      Genome sequences of its diploid ancestors, Arachis duranensis and A. ipaensis,
      were reported, but their SSRs have not been well exploited and utilized hitherto.
      Shelling percentage is an important economic trait and its improvement has been
      one of the major objectives in peanut breeding programs. In this study, the
      genome sequences of A. duranensis and A. ipaensis were used to develop SSR
      markers, and a mapping population (Yuanza 9102 * Xuzhou 68-4) with 195
      recombinant inbred lines was used to map QTLs controlling shelling percentage.
      The numbers of newly developed SSR markers were 84,383 and 120,056 in the A.
      duranensis and A. ipaensis genomes, respectively. Genotyping of the mapping
      population was conducted with both newly developed and previously reported
      markers. QTL analysis using the phenotyping data generated in Wuhan across four
      consecutive years and genotyping data of 830 mapped loci identified 25 QTLs with
      4.46-17.01% of phenotypic variance explained in the four environments. Meta
      analysis revealed five consistent QTLs that could be detected in at least two
      environments. Notably, the consistent QTL cqSPA09 was detected in all four
      environments and explained 10.47-17.01% of the phenotypic variance. The
      segregation in the progeny of a residual heterozygous line confirmed that the
      cpSPA09 locus had additive effect in increasing shelling percentage. These
      consistent and major QTL regions provide opportunity not only for further gene
      discovery, but also for the development of functional markers for breeding.

PMID- 28508099
TI  - Giant congenital melanocytic nevi and malignant transformation: a case for early
      radical intervention.
AB  - The purpose of this paper is to highlight the risk of early malignant
      transformation in infants with giant congenital melanocytic nevi (GN) and
      demonstrate the potential for earlier intervention with aggressive surgery. We
      describe the case of a child born with a GN who developed a metastatic melanoma
      early in life, despite early commencement of resection of the nevus. This is
      contrasted against a second case of a child in which a more radical management
      was conducted. Despite early commencement of serial resection of the GN, the
      first child in this series died of metastatic melanoma prior to complete excision
      of the nevus. With the second child, radical excision combined with the use of
      IntegraTM and negative pressure wound therapy allowed total removal of the GN
      within the first 6 months of life.

PMID- 28508100
TI  - Cervical radiculopathy combined with cervical myelopathy: prevalence and
      characteristics.
AB  - Patients with cervical myelopathy may experience symptoms of radiculopathy, and
      it is not easy to determine whether these symptoms are caused by the myelopathy
      itself or by a radiculopathy accompanied by root compression. Therefore, we aimed
      to investigate the prevalence of radiculopathy combined with cervical myelopathy
      and to evaluate the characteristics of cervical myelopathy with or without
      radiculopathy. We enrolled 127 patients with cervical myelopathy in this
      retrospective study and reviewed their medical records and magnetic resonance
      imaging findings. They were divided into two groups according to the presence of
      cervical radiculopathy, and their age, sex, involved spinal segment, cord signal
      change, surgical method, clinical status were compared, and postsurgical recovery
      was compared using four clinical questionnaires. The incidence and level of
      radiculopathy combined with myelopathy were investigated. Combined cervical
      radiculopathy and myelopathy was diagnosed in 66 patients (51.9%, group 1),
      whereas 61 patients did not have radiculopathy (group 2). There was no difference
      in sex, age, cord signal change, preoperative Japanese Orthopedic Association
      score, neck disability index, and neck visual analogue scale (VAS) between the
      two groups, but group 1 showed higher preoperative arm VAS score (p = 0.001).
      Postoperative arm and neck VAS scores were significantly improved in group 1 (p =
      0.001 and 0.009). Half of the patients had combined cervical myelopathy and
      radiculopathy. A high preoperative arm VAS score was a characteristic of
      radiculopathy combined with myelopathy.

PMID- 28508103
TI  - To be or not to be rheumatologist: survey among Belgian medical students and
      internal medicine trainees: what do certified rheumatologists think about the
      current rheumatology training program?
AB  - In several countries, there have been increasing concerns over the years that
      fewer medical students or trainees choose rheumatology as a specialty. The aim of
      this three-step survey is to study the motivational factors for students and
      trainees in internal medicine to choose for rheumatology as a future career
      option and the idea among experienced rheumatologists about the needs for changes
      in the training program. An online survey was distributed among students in
      medical training (in the final 3 years) and trainees in internal medicine from
      the Ghent University and University Hospital. Questions concerned the level of
      clinical exposure to rheumatology and the motivation about becoming
      rheumatologist. Next, experienced rheumatologists were asked about the needs to
      change the current training. Descriptive data are shown and chi-squared tests
      were calculated to assess differences between groups (based on gender and
      exposure). Logistic regression was performed to study associations between
      demographic variables and choosing rheumatology as career. Only a minority of
      students (17%) and about half of trainees (45%) were ever exposed to
      rheumatology. Only 11% of students and 17% of trainees considered becoming
      rheumatologist. There was no difference in choice based on gender but previous
      exposure seemed to play an important role, and especially during the pre
      specialty years. Univariate logistic regression identified the year of training
      and exposure as predictors for choosing rheumatology. Multivariate analysis only
      retained exposure as significantly associated (odds ratio (95% CI) = 2.88 (1.51
      12.58)). Rheumatology is considered to be a fascinating discipline among Belgian
      students and trainees. Exposure during pre-specialty years is the strongest
      predictor for choosing rheumatology as future career option.

PMID- 28508101
TI  - In-depth clinico-pathological examination of RNA foci in a large cohort of
      C9ORF72 expansion carriers.
AB  - A growing body of evidence suggests that a loss of chromosome 9 open reading
      frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and
      generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral
      sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts
      and dipeptide-repeat proteins have already been examined thoroughly, much remains
      unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we
      performed a comprehensive RNA foci study in an extensive pathological cohort of
      C9ORF72 expansion carriers (n = 63). We evaluated two brain regions using a newly
      developed computer-automated pipeline allowing recognition of cell nuclei and RNA
      foci (sense and antisense) supplemented by manual counting. In the frontal
      cortex, the percentage of cells with sense or antisense RNA foci was 26 or 12%,
      respectively. In the cerebellum, 23% of granule cells contained sense RNA foci
      and 1% antisense RNA foci. Interestingly, the highest percentage of cells with
      RNA foci was observed in cerebellar Purkinje cells (~70%). In general, more cells
      contained sense RNA foci than antisense RNA foci; however, when antisense RNA
      foci were present, they were usually more abundant. We also observed that an
      increase in the percentage of cells with antisense RNA foci was associated with a
      delayed age at onset in the frontal cortex (r = 0.43, p = 0.003), whereas no
      other associations with clinico-pathological features were seen. Importantly, our
      large-scale study is the first to provide conclusive evidence that RNA foci are
      not the determining factor of the clinico-pathological variability observed in
      C9ORF72 expansion carriers and it emphasizes that the distribution of RNA foci
      does not follow the pattern of neurodegeneration, stressing the complex interplay
      between different aspects of C9ORF72-related diseases.

PMID- 28508102
TI  - Role of lymph node dissection during radical nephroureterectomy for upper urinary
      tract urothelial cancer: multi-institutional large retrospective study JCOG1110A.
AB  - PURPOSE: To evaluate the impact of lymph node dissection (LND) on clinical
      outcome during radical nephroureterectomy (RNU) for patients with upper urinary
      tract urothelial cancer (UTUC). METHODS: We, the Urologic Oncology Study Group of
      the Japan Clinical Oncology Group (JCOG), retrospectively collected data from
      patients with non-metastatic UTUC who underwent RNU in 30 centers in 1995-2009.
      Ineligible patients and patients with previous and/or synchronous bladder cancer
      were excluded, and the remaining 2037 patients were analyzed. We compared overall
      and cancer-specific mortality between patients who underwent LND (LND group) and
      those without LND (no-LND group). RESULTS: Among 2037 patients, LND was performed
      in 1046 (51.4%) patients, and 223 (10.9%) patients had pathological node-positive
      (pN+) disease. All-cause mortality was observed in 503 patients (24.7%) during
      follow-up (median 45.8 months), including 363 patients (17.8%) who died of UTUC.
      Patients with pN+ disease showed significantly shorter overall survival (OS)
      compared with pN0 patients, and the estimated 5-year OS for pN+ patients was 30%.
      Older age, >=cT3, and clinical node-positive disease were found as preoperative
      predictors for pN+ disease by multivariate analysis. In the comparison of OS and
      cancer-specific mortality between LND and no-LND groups, there was no significant
      improvement by LND in multivariate analysis. The median number of lymph nodes
      removed was six (IQR 3-11). There was no significant association between the
      number of lymph nodes removed and OS. CONCLUSIONS: The present study indicates
      that there is no therapeutic benefit of LND during RNU for UTUC, although
      pathologically positive LN status can predict poor prognosis.

PMID- 28508105
TI  - Unexplained changes on a psychiatric pregnancy study.

PMID- 28508104
TI  - Quercetin inhibits gout arthritis in mice: induction of an opioid-dependent
      regulation of inflammasome.
AB  - We investigated the anti-inflammatory and analgesic effects of quercetin in
      monosodium urate crystals (MSU)-induced gout arthritis, and the sensitivity of
      quercetin effects to naloxone, an opioid receptor antagonist. Mice were treated
      with quercetin, and mechanical hyperalgesia was assessed at 1-24 h after MSU
      injection. In vivo, leukocyte recruitment, cytokine levels, oxidative stress,
      NFkappaB activation, and gp91phox and inflammasome components (NLRP3, ASC, Pro
      caspase-1, and Pro-IL-1beta) mRNA expression by qPCR were determined in the knee
      joints at 24 h after MSU injection. Inflammasome activation was determined, in
      vitro, in lipopolysaccharide-primed macrophages challenged with MSU. Quercetin
      inhibited MSU-induced mechanical hyperalgesia, leukocyte recruitment, TNFalpha
      and IL-1beta production, superoxide anion production, inflammasome activation,
      decrease of antioxidants levels, NFkappaB activation, and inflammasome components
      mRNA expression. Naloxone pre-treatment prevented all the inhibitory effects of
      quercetin over MSU-induced gout arthritis. These results demonstrate that
      quercetin exerts analgesic and anti-inflammatory effect in the MSU-induced
      arthritis in a naloxone-sensitive manner.

PMID- 28508108
TI  - Stone in ectopic pelvic pancake kidney: a surgical challenge overcome by robotic
      surgery.

PMID- 28508106
TI  - Differential effects of pair housing on voluntary nicotine consumption: a
      comparison between male and female adolescent rats.
AB  - RATIONALE: Tobacco smoking occurs in a wide array of social circumstances. Social
      support for quitting is generally used to stop smoking, while peer interactions
      may be a crucial factor in triggering tobacco use among adolescents. OBJECTIVES:
      To determine the role of social factors on nicotine dependence, we compared
      single- and pair-housed rats subjected to voluntary oral nicotine consumption
      tests. METHODS: Six-week-old adolescent rats were subjected to experimental
      procedures and assigned to one of the following groups: a male single group, a
      male pair group with a sibling, a female single group, and a female pair group
      with a sibling. To measure voluntary nicotine intake, we adopted a two-bottle
      free-choice paradigm for each two days using 25 MUg/ml and 100 MUg/ml nicotine
      solution. RESULTS: There were no differences in change in body weight or food
      intake between the two groups of either sex. Pair-housed female rats showed a
      reduction in nicotine consumption and preference for both low- and high-dose
      nicotine solution, while pair-housed male rats showed only reduced consumption
      and preference for high-dose nicotine solution, but not low-dose solution, as
      compared to single-housed male rats. CONCLUSIONS: Nicotine consumption is sex
      dependently controlled by the social circumstances of rats. This study broadens
      our perspectives on the role of social interactions as a therapeutic strategy to
      treat nicotine addiction-related behaviors depending on sex.

PMID- 28508107
TI  - Memantine add-on to antipsychotic treatment for residual negative and cognitive
      symptoms of schizophrenia: a meta-analysis.
AB  - RATIONALE: We examined whether memantine add-on to antipsychotic treatment is
      beneficial in schizophrenia treatment. OBJECTIVE: This systematic review and meta
      analysis aimed to achieve stronger evidence on the efficacy and safety of
      memantine add-on for treating schizophrenia. METHODS: We analyzed double-blind,
      randomized, placebo-controlled trials of memantine add-on treatment in
      schizophrenia patients receiving antipsychotics. The primary outcomes were
      amelioration of negative symptoms and all-cause discontinuation. Dichotomous
      outcomes are presented as risk ratios (RRs), and continuous outcomes are
      presented as mean differences (MDs) or standardized mean differences (SMDs).
      RESULTS: Eight studies (n = 448) were included. Although memantine add-on
      treatment was superior to placebo for ameliorating negative symptoms (SMD = 
      0.96, p = 0.006, I 2 = 88%; N = 7, n = 367) in the Positive and Negative Syndrome
      Scale general subscale (MD = -1.62, p = 0.002, I 2 = 0%; N = 4, n = 151) and Mini
      Mental Status Examination score (MD = -3.07, p < 0.0001, I 2 = 21%; N = 3, n =
      83), there were no statistically significant differences in the amelioration of
      overall (SMD = -0.75, p = 0.06, I 2  = 86%; N = 5, n = 271), positive (SMD = 
      0.46, p = 0.07, I 2 = 80%; N = 7, n = 367), and depressive symptoms (SMD = 
      0.127, p = 0.326, I 2 = 0%; N = 4, n = 201); all-cause discontinuation (RR =
      1.34, p = 0.31, I 2 = 0%; N = 8, n = 448); and individual adverse events
      (fatigue, dizziness, headache, nausea, constipation) between the groups. For
      negative symptoms, the significant heterogeneity disappeared when risperidone
      studies alone were considered (I 2 = 0%). However, memantine add-on treatment
      remained superior to placebo (SMD = -1.29, p = 0.00001). Meta-regression analysis
      showed that patient age was associated with memantine-associated amelioration of
      negative symptoms (slope = 0.171, p = 0.0206). CONCLUSIONS: Memantine add-on
      treatment may be beneficial for treating psychopathological symptoms (especially
      negative symptoms) in schizophrenia patients. The negative-symptom effect size
      may be associated with younger adult schizophrenia patients.

PMID- 28508109
TI  - Solvent-accessibility of discrete residue positions in the polypeptide hormone
      glucagon by 19F-NMR observation of 4-fluorophenylalanine.
AB  - The amino acid 4-fluoro-L-phenylalanine (4F-Phe) was introduced at the positions
      of Phe6 and Phe22 in the 29-residue polypeptide hormone glucagon by expressing
      glucagon in E. coli in the presence of an excess of 4F-Phe. Glucagon regulates
      blood glucose homeostasis by interaction with the glucagon receptor (GCGR), a
      class B GPCR. By referencing to the 4F-Phe chemical shifts at varying D2O
      concentrations, the solvent exposure of the two Phe sites along the glucagon
      sequence was determined, showing that 4F-Phe6 was fully solvent exposed and 4F
      Phe22 was only partially exposed. The incorporation of fluorine atoms in
      polypeptide hormones paves the way for novel studies of their interactions with
      membrane-spanning receptors, specifically by differentiating between effects on
      the solvent accessibility, the line shapes, and the chemical shifts from
      interactions with lipids, detergents and proteins. Studies of interactions of
      GCGR with ligands in solution is at this point of keen interest, given that
      recent crystallographic studies revealed that an apparent small molecule
      antagonist actually binds as an allosteric effector at a distance of ~20 A from
      the orthosteric ligand binding site (Jazayeri et al., in Nature 533:274-277,
      2016).

PMID- 28508110
TI  - Joint non-uniform sampling of all incremented time delays for quicker acquisition
      in protein relaxation studies.
AB  - NMR relaxometry plays crucial role in studies of protein dynamics. The
      measurement of longitudinal and transverse relaxation rates of [Formula: see
      text]N is the main source of information on backbone motions. However, even the
      most basic approach exploiting a series of [Formula: see text]N HSQC spectra can
      require several hours of measurement time. Standard non-uniform sampling (NUS),
      i.e. random under-sampling of indirect time domain, typically cannot reduce this
      by more than 2-4[Formula: see text] due to relatively low "compressibility" of
      these spectra. In this paper we propose an extension of NUS to relaxation delays.
      The two-dimensional space of [Formula: see text]/[Formula: see text] is sampled
      in a way similar to NUS of [Formula: see text]/[Formula: see text] domain in 3D
      spectra. The signal is also processed in a way similar to that known from 3D NUS
      spectra i.e. using one of the most popular compressed sensing algorithms,
      iterative soft thresholding. The 2D Fourier transform matrix is replaced with
      mixed inverse Laplace-Fourier transform matrix. The peak positions in resulting
      3D spectrum are characterized by two frequency coordinates and relaxation rate
      and thus no additional fitting of exponential curves is required. The method is
      tested on three globular proteins, providing satisfactory results in a time
      corresponding to acquisition of two conventional [Formula: see text]N HSQC
      spectra.

PMID- 28508111
TI  - Effect of high-intensity aerobic exercise on aerobic fitness and HbA1c in
      patients with type 2 diabetes.

PMID- 28508112
TI  - Response to comments on "High-intensity aerobic interval training improves
      aerobic fitness and HbA1c among persons diagnosed with type 2 diabetes".

PMID- 28508113
TI  - Doubly labelled water assessment of energy expenditure: principle, practice, and
      promise.
AB  - The doubly labelled water method for the assessment of energy expenditure was
      first published in 1955, application in humans started in 1982, and it has become
      the gold standard for human energy requirement under daily living conditions. The
      method involves enriching the body water of a subject with heavy hydrogen (2H)
      and heavy oxygen (18O), and then determining the difference in washout kinetics
      between both isotopes, being a function of carbon dioxide production. In
      practice, subjects get a measured amount of doubly labelled water (2H 218 O) to
      increase background enrichment of body water for 18O of 2000 ppm with at least
      180 ppm and background enrichment of body water for 2H of 150 ppm with 120 ppm.
      Subsequently, the difference between the apparent turnover rates of the hydrogen
      and oxygen of body water is assessed from blood-, saliva-, or urine samples,
      collected at the start and end of the observation interval of 1-3 weeks. Samples
      are analyzed for 18O and 2H with isotope ratio mass spectrometry. The doubly
      labelled water method is the indicated method to measure energy expenditure in
      any environment, especially with regard to activity energy expenditure, without
      interference with the behavior of the subjects. Applications include the
      assessment of energy requirement from total energy expenditure, validation of
      dietary assessment methods and validation of physical activity assessment methods
      with doubly labelled water measured energy expenditure as reference, and studies
      on body mass regulation with energy expenditure as a determinant of energy
      balance.

PMID- 28508115
TI  - When kinesthetic information is neglected in learning a Novel bimanual rhythmic
      coordination.
AB  - Many studies have shown that rhythmic interlimb coordination involves perception
      of the coupled limb movements, and different sensory modalities can be used.
      Using visual displays to inform the coupled bimanual movement, novel bimanual
      coordination patterns can be learned with practice. A recent study showed that
      similar learning occurred without vision when a coach provided manual guidance
      during practice. The information provided via the two different modalities may be
      same (amodal) or different (modality specific). If it is different, then learning
      with both is a dual task, and one source of information might be used in
      preference to the other in performing the task when both are available. In the
      current study, participants learned a novel 90 degrees  bimanual coordination
      pattern without or with visual information in addition to kinesthesis. In
      posttest, all participants were tested without and with visual information in
      addition to kinesthesis. When tested with visual information, all participants
      exhibited performance that was significantly improved by practice. When tested
      without visual information, participants who practiced using only kinesthetic
      information showed improvement, but those who practiced with visual information
      in addition showed remarkably less improvement. The results indicate that (1) the
      information is not amodal, (2) use of a single type of information was preferred,
      and (3) the preferred information was visual. We also hypothesized that older
      participants might be more likely to acquire dual task performance given their
      greater experience of the two sensory modes in combination, but results were
      replicated with both 20- and 50-year-olds.

PMID- 28508114
TI  - Oral L-menthol reduces thermal sensation, increases work-rate and extends time to
      exhaustion, in the heat at a fixed rating of perceived exertion.
AB  - PURPOSE: The study investigated the effect of a non-thermal cooling agent, L
      menthol, on exercise at a fixed subjective rating of perceived exertion (RPE) in
      a hot environment. METHOD: Eight male participants completed two trials at an
      exercise intensity between 'hard' and 'very hard', equating to 16 on the RPE
      scale at ~35  degrees C. Participants were instructed to continually adjust their
      power output to maintain an RPE of 16 throughout the exercise trial, stopping
      once power output had fallen by 30%. In a randomized crossover design, either L
      menthol or placebo mouthwash was administered prior to exercise and at 10 min
      intervals. Power output, [Formula: see text]O2, heart rate, core and skin
      temperature was monitored, alongside thermal sensation and thermal comfort.
      Isokinetic peak power sprints were conducted prior to and immediately after the
      fixed RPE trial. RESULTS: Exercise time was greater (23:23 +/- 3:36 vs. 21:44 +/-
      2:32 min; P = 0.049) and average power output increased (173 +/- 24 vs. 167 +/-
      24 W; P = 0.044) in the L-menthol condition. Peak isokinetic sprint power
      declined from pre-post trial in the L-menthol l (9.0%; P = 0.015) but not in the
      placebo condition (3.4%; P = 0.275). Thermal sensation was lower in the L-menthol
      condition (P = 0.036), despite no changes in skin or core temperature (P > 0.05).
      CONCLUSION: These results indicate that a non-thermal cooling mouth rinse lowered
      thermal sensation, resulting in an elevated work rate, which extended exercise
      time in the heat at a fixed RPE.

PMID- 28508116
TI  - Comparing visual search and eye movements in bilinguals and monolinguals.
AB  - Recent research has suggested that bilinguals show advantages over monolinguals
      in visual search tasks, although these findings have been derived from global
      behavioral measures of accuracy and response times. In the present study we
      sought to explore the bilingual advantage by using more sensitive eyetracking
      techniques across three visual search experiments. These spatially and temporally
      fine-grained measures allowed us to carefully investigate any nuanced attentional
      differences between bilinguals and monolinguals. Bilingual and monolingual
      participants completed visual search tasks that varied in difficulty. The
      experiments required participants to make careful discriminations in order to
      detect target Landolt Cs among similar distractors. In Experiment 1, participants
      performed both feature and conjunction search. In Experiments 2 and 3,
      participants performed visual search while making different types of speeded
      discriminations, after either locating the target or mentally updating a
      constantly changing target. The results across all experiments revealed that
      bilinguals and monolinguals were equally efficient at guiding attention and
      generating responses. These findings suggest that the bilingual advantage does
      not reflect a general benefit in attentional guidance, but could reflect more
      efficient guidance only under specific task demands.

PMID- 28508117
TI  - Single-Center Experience Using the 3MAX Reperfusion Catheter for the Treatment of
      Acute Ischemic Stroke with Distal Arterial Occlusions.
AB  - PURPOSE: Most recent guidelines recommend the use of stent retriever devices in
      endovascular treatment of acute ischemic stroke with large vessel occlusion
      (LVO). Recently published data reported convincing results with thromboaspiration
      devices such as the Penumbra System (Penumbra, Alameda, CA, USA) combined with
      supple reperfusion catheters by using the ADAPT (A Direct Aspiration First-Pass
      Thrombectomy) technique. The aim of this study was to report our initial
      experience with the 3MAX (3.8 F) reperfusion catheter for the recanalization of
      distal intracranial arteries. METHODS: From August 2015 to December 2016, 32
      consecutive patients (16 females, 50%; mean age = 67.4 +/- 18.7 years, range: 22
      91) for 38 distal occlusions underwent mechanical thrombectomy (MT) by
      thromboaspiration using the 3MAX. Median NIHSS score at admission was 14 (IQR: 9
      19). Distal occlusions were distributed as follows: M2 (n: 23), M3 (n: 6), P1 (n:
      3), P2 (n: 2), P3 (n: 2), A3 segment (n: 1) and superior cerebellar artery (n:
      1). RESULTS: In 1/38 (2.6%) target artery, the 3MAX could not be navigated. Of
      the 37 (59.5%) remaining arteries, 22 were successfully reperfused (TICI 2b/3)
      after ADAPT with the 3MAX alone. Additional stent retriever thrombectomy allowed
      a 76.3% final reperfusion rate. Good functional outcome (mRS <=2) was obtained in
      45.5% of patients at 3 months. Three (9.4%) 3MAX-related complications occurred:
      2 emboli to new territory (ENT) and one vascular perforation. CONCLUSIONS: The
      3MAX is well-navigable in distal arteries making it useful as a frontline
      technique. However, the reperfusion rate with the 3MAX catheter alone seems lower
      than the ones reported with stent retrievers for such distal occlusions.

PMID- 28508118
TI  - Effects of aeration on metabolic profiles of Mortierella alpina during the
      production of arachidonic acid.
AB  - To investigate the metabolic regulation against oxygen supply, comparative
      metabolomics was performed to explore the metabolic responses of Mortierella
      alpina in the process of arachidonic acid (ARA) production. More than 110
      metabolites involved in Embden-Meyerhof-Parnas pathway, pentose phosphate
      pathway, tricarboxylic acid cycle, inositol phosphate metabolism, fatty acid
      biosynthesis, and amino acid metabolism were identified by gas chromatography
      mass spectrometry. Samples at different aeration rates were clearly distinguished
      by principal components analysis and partial least squares analysis, indicating
      that oxygen supply had a profound effect on the metabolism of M. alpina. Eleven
      major metabolites were identified as potential biomarkers to be primarily
      responsible for the difference of metabolism. Further study of metabolic changes
      with the relevant pathways demonstrated that the levels of several intermediate
      metabolites in relation to central carbon metabolism changed remarkably via both
      processes and citrate and malate was supposed to play vital roles in
      polyunsaturated acid (PUFA) synthesis. Increase of myo-inositol and sorbitol were
      probably for osmo-regulation and redox balance, while enhanced phosphoric acid
      and pyroglutamic acid were supposed to have function in the activation of signal
      transduction pathway for stress resistance. The present study provides a novel
      insight into the metabolic responses of M. alpina to aeration rates and the
      metabolic characteristics during the ARA fermentation.

PMID- 28508119
TI  - Lipoprotein(a): A Lipoprotein Whose Time Has Come.
AB  - OPINION STATEMENT: Cardiovascular disease is a leading cause of morbidity and
      mortality in the USA and around the world. While we are now able to achieve
      significant low-density lipoprotein cholesterol (LDL-C) lowering with current
      therapies, many patients remain at risk for cardiovascular disease (CVD).
      Elevated lipoprotein(a) [Lp(a)] has been shown to be an independent risk factor
      for CVD and accounts for some of the residual CVD risk after LDL-C lowering in
      several large clinical trials. Moreover, there is now strong evidence supporting
      the causal relationship between Lp(a) and aortic stenosis as well as peripheral
      arterial disease. Despite the growing interest in this lipoprotein, the current
      therapeutic options for Lp(a) reduction are limited. Our general approach in
      patients with elevated Lp(a) levels is to aggressively manage other modifiable
      cardiovascular risk factors including lifestyle modification, consideration of
      aspirin therapy, and LDL-C lowering. Unfortunately, there are conflicting reports
      on how effective this strategy is at reducing the risk for cardiovascular events
      attributed to elevated Lp(a). As a result, targeted Lp(a)-lowering strategies are
      needed. Lp(a) therapeutics is an active area of research with several promising
      classes of pharmacotherapies under investigation to address this causal
      biomarker.

PMID- 28508120
TI  - Effects of arm truncation on the appearance of the halo artifact in 68Ga-PSMA-11
      (HBED-CC) PET/MRI.
AB  - PURPOSE: PSMA ligand imaging with hybrid PET/MRI scanners could be an integral
      part of the clinical routine in the future. However, the first study about this
      novel method revealed a severe photopenic artifact ("halo artifact") around the
      urinary bladder causing significantly reduced tumor visibility. The aim of this
      evaluation was to analyze the role of arm truncation on the appearance of the
      halo artifact in 68Ga-PSMA-11 PET/MRI hypothesizing that this influences the
      appearance. METHODS: Twenty-seven consecutive patients were subjected to 68Ga
      PSMA-11 PET/CT (1 h p.i.) followed by PET/MRI (3 h p.i.). PET/MRI was first
      started with scans of the abdomen to pelvis with arms positioned up above the
      head. Immediately thereafter, additional scans from the pelvis to abdomen were
      conducted with arms positioned down beside the trunk. All investigations were
      first analyzed separately and then compared with respect to tumor detection and
      tumor uptake (SUV) as well as the presence and intensity of the halo artifact.
      The Wilcoxon signed rank test was used to determine statistical differences
      including Bonferroni correction. RESULTS: The halo was significantly reduced if
      the arms were elevated. Lesions inside the halo artifact (n = 16) demonstrated
      significantly increased SUVmean (p = 0.0007) and SUVmax (p = 0.0024) with arms
      positioned up. The halo appearance and intensity was not dependent on the total
      activity and activity concentration of the urinary bladder. CONCLUSION:
      Positioning the arms down was shown to be significantly associated with the
      appearance of the halo artifact in PET/MRI. Positioning the arms up above the
      head can significantly reduce the halo artifact, thereby detecting more tumor
      lesions.

PMID- 28508121
TI  - Overexpression of SmMYB9b enhances tanshinone concentration in Salvia
      miltiorrhiza hairy roots.
AB  - KEY MESSAGE: A Salvia miltiorrhiza R2R3-MYB gene, SmMYB9b , has been cloned and
      characterized. Overexpression of SmMYB9b resulted in a significant improvement of
      tanshinones, the lipophilic active ingredients in danshen hairy roots. Plant R2R3
      MYB transcription factors play important roles in various physiological and
      biochemical processes. Danshen (Salvia miltiorrhiza bunge) is a valuable
      medicinal herb with tanshinones and salvianolic acids as the principal bioactive
      ingredients. A number of putative R2R3-MYB transcription factors have been
      identified in the plant, but their function remains to be studied. Here, we
      report the cloning of SmMYB9b, an S20 R2R3-MYB member and its regulatory
      properties. SmMYB9b contains an open reading frame of 792 bp in length and
      encodes a 264-amino acid protein. Its transcripts were most abundant in blooming
      flowers (except for calyces) and increased with flower development. Exogenous
      abscisic acid strongly activated its transcription. Gibberellins and methyl
      jasmonate also showed a time-dependent activation effect on its transcription,
      but to a weaker degree. Overexpression of SmMYB9b in danshen hairy roots enhanced
      tanshinone concentration to 2.16 +/- 0.39 mg/g DW, a 2.2-fold improvement over
      the control. In addition to increased tanshinone concentration, the hairy root
      growth and lateral hairy root formation were also suppressed. KEGG pathway
      enrichment analysis with de novo RNAseq data indicated that stress-response
      related metabolic pathways, such as the terpenoid and plant hormone signal
      transduction pathways, were significantly enriched, implying possible implication
      of SmMYB9b in such processes. Quantitative RT-PCR analysis showed that the
      transcription of terpenoid biosynthetic genes SmDXS2, SmDXR, SmGGPPS, and SmKSL1
      was significantly up-regulated in danshen hairy roots over expressing SmMYB9b.
      These data suggest that overexpression of SmMYB9b results in enhanced tanshinone
      concentration through stimulation of the MEP pathway. The present findings shed
      new light on elucidating the roles of R2R3-MYB in the biosynthesis of
      diterpenoids in S. miltiorrhiza.

PMID- 28508123
TI  - Photochemically Controlled Drug Dosing from a Polymeric Scaffold.
AB  - PURPOSE: To develop the first photoactive biomaterial coating capable of
      controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin
      (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. METHODS:
      Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and
      characterised via NMR spectroscopy and mass spectrometry following
      chromatographic purification. Conjugate photolysis was investigated in
      acetonitrile solution and within the pMEA matrix following exposure to low-power
      365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered
      saline was monitored using UV-vis spectroscopy. RESULTS: The synthetic procedures
      yielded the desired drug conjugates with full supporting characterisation. Drug
      regeneration through photolysis of the synthesised conjugates was successful in
      both acetonitrile solution and within the pMEA scaffold upon UV irradiation.
      Conjugates were retained within the pMEA scaffold with exclusive drug liberation
      following irradiation and increased drug dose with increasing exposure. Multi
      dosing capacity was demonstrated though the ability of successive irradiation
      periods to generate further bursts of drug. CONCLUSION: This study demonstrates
      the first application of photochemically controlled drug release from a
      biomaterial coating and the feasibility of using pMEA as a scaffold for housing
      the photoactive drug-DMB conjugates.

PMID- 28508122
TI  - A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch
      Nyhan Disease.
AB  - PURPOSE: Because of the evolutionary loss of the uricolytic pathway, humans
      accumulate poorly soluble urate as the final product of purine catabolism.
      Restoration of uricolysis through enzyme therapy is a promising treatment for
      severe hyperuricemia caused by deficiency of hypoxanthine-guanine
      phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG
      conjugation on the activity and stability of the enzymatic complement required
      for conversion of urate into the more soluble (S)-allantoin. METHODS: We produced
      in recombinant form three zebrafish enzymes required in the uricolytic pathway.
      We carried out a systematic study of the effect of PEGylation on the function and
      stability of the three enzymes by varying PEG length, chemistry and degree of
      conjugation. We assayed in vitro the uricolytic activity of the PEGylated
      enzymatic triad. RESULTS: We defined conditions that allow PEGylated enzymes to
      retain native-like enzymatic activity even after lyophilization or prolonged
      storage. A combination of the three enzymes in an appropriate ratio allowed
      efficient conversion of urate to (S)-allantoin with no accumulation of
      intermediate metabolites. CONCLUSIONS: Pharmaceutical restoration of the
      uricolytic pathway is a viable approach for the treatment of severe
      hyperuricemia.

PMID- 28508125
TI  - Judgement bias in pigs is independent of performance in a spatial holeboard task
      and conditional discrimination learning.
AB  - Biases in judgement of ambiguous stimuli, as measured in a judgement bias task,
      have been proposed as a measure of the valence of affective states in animals. We
      recently suggested a list of criteria for behavioural tests of emotion, one of
      them stating that responses on the task used to assess emotionality should not be
      confounded by, among others, differences in learning capacity, i.e. must not
      simply reflect the cognitive capacity of an animal. We performed three
      independent studies in which pigs acquired a spatial holeboard task, a free
      choice maze which simultaneously assesses working memory and reference memory.
      Next, pigs learned a conditional discrimination between auditory stimuli
      predicting a large or small reward, a prerequisite for assessment of judgement
      bias. Once pigs had acquired the conditional discrimination task, optimistic
      responses to previously unheard ambiguous stimuli were measured in the judgement
      bias task as choices indicating expectation of the large reward. We found that
      optimism in the judgement bias task was independent of all three measures of
      learning and memory indicating that the performance is not dependent on the pig's
      cognitive abilities. These results support the use of biases in judgement as
      proxy indicators of emotional valence in animals.

PMID- 28508126
TI  - What's the point? Golden and Labrador retrievers living in kennels do not
      understand human pointing gestures.
AB  - In many studies that have investigated whether dogs' capacities to understand
      human pointing gestures are aspects of evolutionary or developmental social
      competences, family-owned dogs have been compared to shelter dogs. However, for
      most of these studies, the origins of shelter dogs were unknown. Some shelter
      dogs may have lived with families before entering shelters, and from these past
      experiences, they may have learned to understand human gestures. Furthermore,
      there is substantial variation in the methodology and analytic approaches used in
      such studies (e.g. different pointing protocols, different treatment of trials
      with no-choice response and indoor vs. outdoor experimental arenas). Such
      differences in methodologies and analysis techniques used make it difficult to
      compare results obtained from different studies and may account for the divergent
      results obtained. We thus attempted to control for several parameters by carrying
      out a test on dynamic proximal and distal pointing. We studied eleven kennel dogs
      of known origin that were born and raised in a kennels with limited human
      interaction. This group was compared to a group of eleven dogs comparable in
      terms of breed, sex and age that had lived with human families since they were
      puppies. Our results demonstrate that pet dogs outperform kennel dogs in their
      comprehension of proximal and distal pointing, regardless of whether trials where
      no-choice was made were considered as errors or were excluded from statistical
      analysis, meaning that dogs living in kennels do not understand pointing
      gestures. Even if genetic effects of the domestication process on human-dog
      relationships cannot be considered as negligible, our data suggest that dogs need
      to learn human pointing gestures and thus underscore the importance of
      ontogenetic processes.

PMID- 28508124
TI  - DNA hypermethylation of sFRP5 contributes to indoxyl sulfate-induced renal
      fibrosis.
AB  - : Renal fibrosis is the most common outcome of chronic kidney disease (CKD),
      while the pathogenesis of renal fibrosis is not fully understood. In this study,
      we first showed that the progress of renal fibrosis was positively related to
      serum levels of indoxyl sulfate, a typical protein-bound toxin, and that there
      was a close correlation between serum indoxyl sulfate levels and beta-catenin
      expression in the kidneys (r = 0.908, p < 0.001) of CKD patients. We then
      demonstrated that intraperitoneal injections of indoxyl sulfate (100 mg/kg/day)
      for 4 weeks in uninephrectomized mice explicitly induced renal fibrosis, which
      was accompanied by a significant activation of Wnt/beta-catenin signaling. In
      vitro investigations in human renal tubular HK-2 cells revealed that indoxyl
      sulfate exhibited a potent ability to induce Wnt/beta-catenin activation through
      the downregulation of sFRP5, a gene that codes for an extracellular antagonist of
      Wnt signaling, by increasing the DNA methylation level of its promoter CpG
      islands. The increased expression of DNA methyltransferases following the
      activation of ROS/ERK1/2 signaling was responsible for the DNA hypermethylation
      of sFRP5 induced by indoxyl sulfate. Conversely, treatment with 5-aza-2'
      deoxycytidine, an inhibitor of DNA methyltransferases, significantly reduced
      indoxyl sulfate-induced sFRP5 downregulation and Wnt/beta-catenin activation. In
      vivo, intraperitoneal injections of recombinant sFRP5 protein or 5-aza-2'
      deoxycytidine substantially alleviated renal fibrosis in indoxyl sulfate-treated
      uninephrectomized mice. Our results suggest that indoxyl sulfate promotes renal
      fibrosis through the induction of DNA hypermethylation of sFRP5, and thereafter
      the activation of Wnt/beta-catenin signaling. These findings provide new insights
      into the pathogenesis of renal fibrosis in CKD patients. KEY MESSAGES: IS induces
      renal fibrosis by increasing beta-catenin expression in CKD mice. IS-induced Wnt
      signaling activation is due to sFRP5 hypermethylation in HK-2 cells. ROS/ERK1/2
      signaling activation is involved in IS-induced sFRP5 hypermethylation. sFRP5
      upregulation attenuates IS-induced renal fibrosis by inhibiting Wnt signaling.

PMID- 28508127
TI  - Transcending Landscapes: Working Across Scales and Levels in Pastoralist
      Rangeland Governance.
AB  - Landscape approaches can be subjected to mistakenly targeting a single "best"
      level of governance, and paying too little attention to the role that cross-scale
      and cross-level interactions play in governance. In rangeland settings,
      resources, patterns of use of those resources, and the institutions for managing
      the resources exist at multiple levels and scales. While the scholarship on
      commons offers some guidance on how to conceptualize governance in rangeland
      landscapes, some elements of commons scholarship-notably the "design principles"
      for effective governance of commons-do not seem to apply neatly to governance in
      pastoralist rangeland settings. This paper examines three cases where attempts
      have been made to foster effective landscape governance in such settings to
      consider how the materiality of commons influences the nature of cross-scale and
      cross-level interactions, and how these interactions affect governance. In all
      three cases, although external actors seemed to work appropriately and
      effectively at community and landscape levels, landscape governance mechanisms
      have been facing great challenges arising from relationships beyond the
      landscape, both vertically to higher levels of decision-making and horizontally
      to communities normally residing in other landscapes. The cases demonstrate that
      fostering effective landscape-level governance cannot be accomplished only
      through action at the landscape level; it is a task that must be pursued at
      multiple levels and in relation to the connections across scales and levels. The
      paper suggests elements of a conceptual framework for understanding cross-level
      and cross-scale elements of landscape governance, and offers suggestions for
      governance design in pastoralist rangeland settings.

PMID- 28508129
TI  - Development and Characterization of Magnetite/Poly(butylcyanoacrylate)
      Nanoparticles for Magnetic Targeted Delivery of Cancer Drugs.
AB  - A great attention is presently paid to the design of drug delivery vehicles based
      on surface-modified magnetic nanoparticles. They can, in principle, be directed
      to a desired target area for releasing their drug payload, a process triggered by
      pH, temperature, radiation, or even magnetic field. To this, the possibility of
      forming part of diagnostic tools by enhanced magnetic resonance imaging or that
      of further treatment by magnetic hyperthermia can be added. Bare particles are
      rapidly eliminated from the bloodstream by the phagocyte mononuclear system,
      leading to short biological half-life. It is hence required to coat them in order
      to increase their biocompatibility and facilitate the drug incorporation. In this
      work, magnetite nanoparticles were coated with poly(butylcyanoacrylate) (PBCA)
      manufactured and characterized with regard to their physical properties and their
      suitability as a platform for magnetically controlled drug delivery. The average
      diameter of magnetite and core-shell nanoparticles was 97 +/- 19 and 140 +/- 20
      nm, respectively. Infrared analysis, electrophoretic mobility, surface
      thermodynamics analysis, and X-ray diffraction all confirmed that the magnetic
      particles were sufficiently covered by the polymer in the composite
      nanoparticles. In addition, assays using normal (CCD-18 and MCF-10A) and tumoral
      (T-84 and MCF-7) cell lines derived from colon and breast tissue, respectively,
      demonstrated that nanocomposites have low or negligible cytotoxicity. It is
      concluded that PBCA-coated magnetite core-shell nanoparticles represent a
      remarkable promise as a platform for magnetically controlled drug delivery.

PMID- 28508128
TI  - The cardiothoracic ratio and all-cause and cardiovascular disease mortality in
      patients undergoing maintenance hemodialysis: results of the MBD-5D study.
AB  - BACKGROUND: The cardiothoracic ratio (CTR) is a non-invasive left ventricular
      hypertrophy index. However, whether CTR associates with cardiovascular disease
      (CVD) and mortality in hemodialysis (HD) populations is unclear. METHODS: Using a
      Mineral and Bone disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD
      5D Study) subcohort, 2266 prevalent HD patients (age 62.8 years, female 38.0%, HD
      duration 9.4 years) with secondary hyperparathyroidism (SHPT) whose baseline CTR
      had been recorded were selected. We evaluated associations between CTR and all
      cause death, CVD death, or composite events in HD patients. RESULTS: CTR was
      associated significantly with various background and laboratory characteristics.
      All-cause death, CVD-related death, and composite events increased across the CTR
      quartiles (Q). Adjusted hazard risk (HR) for all-cause death was 1.4 (95%
      confidential interval, 0.9-2.1) in Q2, 1.9 (1.3-2.9) in Q3, and 2.6 (1.7-4.0) in
      Q4, respectively (Q1 as a reference). The corresponding adjusted HR for CVD
      related death was 1.8 (0.8-4.2), 3.1 (1.4-6.8), and 3.5 (1.6-7.9), and that for
      composite outcome was 1.2 (1.0-1.6), 1.7 (1.3-2.2), and 1.8 (1.5-2.3),
      respectively.  Exploratory analysis revealed that there were relationships
      between CTR and age, sex, body mass index, comorbidity of CVD, dialysis duration
      and intact parathyroid hormone, phosphorus, hemoglobin, and usage of phosphate
      binder [corrected]. CONCLUSION: CTR correlated with all-cause death, CVD death,
      and composite events in HD patients with SHPT.

PMID- 28508130
TI  - Atmospheric conditions create freeways, detours and tailbacks for migrating
      birds.
AB  - The extraordinary adaptations of birds to contend with atmospheric conditions
      during their migratory flights have captivated ecologists for decades. During the
      21st century technological advances have sparked a revival of research into the
      influence of weather on migrating birds. Using biologging technology, flight
      behaviour is measured across entire flyways, weather radar networks quantify
      large-scale migratory fluxes, citizen scientists gather observations of migrant
      birds and mechanistic models are used to simulate migration in dynamic aerial
      environments. In this review, we first introduce the most relevant microscale,
      mesoscale and synoptic scale atmospheric phenomena from the point of view of a
      migrating bird. We then provide an overview of the individual responses of
      migrant birds (when, where and how to fly) in relation to these phenomena. We
      explore the cumulative impact of individual responses to weather during
      migration, and the consequences thereof for populations and migratory systems. In
      general, individual birds seem to have a much more flexible response to weather
      than previously thought, but we also note similarities in migratory behaviour
      across taxa. We propose various avenues for future research through which we
      expect to derive more fundamental insights into the influence of weather on the
      evolution of migratory behaviour and the life-history, population dynamics and
      species distributions of migrant birds.

PMID- 28508131
TI  - Muscle wasting in chronic kidney disease.
AB  - Loss of lean body mass is a relevant component of the cachexia, or protein energy
      wasting (PEW), syndrome. Reduced muscle mass seems to be the most solid criterion
      for the presence of cachexia/PEW in patients with chronic kidney disease (CKD),
      and those with greater muscle mass loss have a higher risk of death. Children
      with CKD have many risk factors for lean mass and muscle wasting, including poor
      appetite, inflammation, growth hormone resistance, and metabolic acidosis.
      Mortality risks in patients with CKD increases as body mass index (BMI) and
      weight decreases. However, data regarding cachexia/PEW and muscle wasting in
      children with CKD is scarce due to lack of consensus in diagnostic criteria and
      an appropriate investigative methodology. Further research is urgently needed to
      address this important complication in the pediatric CKD setting, which may have
      fundamental impact on clinical outcomes.

PMID- 28508133
TI  - Children and Adolescents Macrovascular Reactivity Level and Dynamics, But Not the
      Microvascular Response, is Associated with Body Mass Index and Arterial Stiffness
      Levels.
AB  - INTRODUCTION: The existing evidence indicates that primary prevention of
      atherosclerotic disease should begin in childhood. Detection of children and
      adolescents at risk for atherosclerosis may allow early intervention to decrease
      the atherosclerotic process, thereby preventing or delaying cardiovascular
      disease. Vascular reactivity (VR) is altered even by early atherosclerosis.
      Obesity is a main cardiovascular risk factor (CVRF) observed in childhood. If
      childhood obesity associates impaired macro and/or micro VR is controversial.
      AIMS: To characterize macro and micro VR analyzing the stimulus and vascular
      response temporal profiles in children and adolescents considering their body
      mass index (BMI); and to assess potential associations between subjects'
      characteristics and the hyperemic stimulus and/or VR. METHODS: Healthy subjects
      (n = 99, age 5-17 years, female 46%) were included. Considering the BMI, normal,
      overweight and obese groups were defined. CVRF exposure was assessed. Brachial
      flow-mediated dilation and reactive hyperemia, associated with transient ischemia
      (forearm cuff-inflation) were evaluated. Diameter, flow velocities, resistive
      indexes and shear-stress were determined before, during and after cuff-release.
      Complimentary VR indexes were computed. Aortic stiffness and aortic and brachial
      blood pressure were determined. RESULTS: Obese showed the lowest and slowest
      macrovascular response (p < 0.05). Micro VR was not associated with obesity.
      Higher aortic stiffness levels were associated with slower macrovascular
      responses (p < 0.05). CONCLUSION: Childhood obesity associates not only reduced,
      but also slowed macrovascular reactivity. Microvascular response to transient
      ischemia is preserved in obese children. Macro and microvascular responses would
      be non-associated phenomena in childhood. During childhood, VR dynamics would
      depend on the arterial stiffness.

PMID- 28508132
TI  - Survival in children requiring chronic renal replacement therapy.
AB  - Survival in the pediatric end-stage renal disease (ESRD) population has improved
      substantially over recent decades. Nonetheless, mortality remains at least 30
      times higher than that of healthy peers. Patient survival is multifactorial and
      dependent on various patient and treatment characteristics and degree of economic
      welfare of the country in which a patient is treated. In this educational review,
      we aim to delineate current evidence regarding mortality risk in the pediatric
      ESRD population and provide pediatric nephrologists with up-to-date information
      required to counsel affected families.

PMID- 28508134
TI  - Effect of Combat Stress in the Psychophysiological Response of Elite and Non
      Elite Soldiers.
AB  - We aimed to analyse the effect of combat stress in the psychophysiological
      responses of elite and non-elite soldiers. We analysed heart rate, cortical
      arousal, skin temperature, blood lactate concentration and lower body muscular
      strength before and after a tactical combat simulation in 40 warfighters divided
      in two groups: elite (n: 20; 28.5 +/- 6.38 years) and non-elite (n:20; 31.94 +/-
      6.24 years) group. Elite presented a significantly higher lactate concentration
      after combat than non elite soldiers (3.8 +/- 1.5 vs 6.6 +/- 1.3 mmol/L). Non
      elite soldiers had a higher heart rate pre and post the simulation than elite
      (82.9 +/- 12.3 vs 64.4 +/- 11. pre non elite and elite respectively; 93.0 +/-
      12.8 vs 88 +/- 13.8 bpm post non elite and elite respectively). Elite soldiers
      presented higher lower muscular strength than elite in all test and before and
      after the combat simulation. Cortical arousal was not modified significantly in
      both groups. We conclude elite soldiers presented in combat a higher anaerobic
      metabolism activation and muscular strength than non-elite soldiers, but
      cardiovascular, cortical, and muscular strength manifestation presented the same
      response in both elite and non-elite soldiers.

PMID- 28508136
TI  - A fixed correction of absolute transpulmonary pressure may not be ideal for
      clinical use : Discussion on "Accuracy of esophageal pressure to assess
      transpulmonary pressure during mechanical ventilation".

PMID- 28508137
TI  - The fractal lightning burn results from a positively charged strike : Discussion
      on "Resuscitated unconscious male: Lichtenberg's sign lighting the way".

PMID- 28508138
TI  - Prevalence and Risk Factors Associated with Forced-Sex Among South African High
      School Students.
AB  - Sexual violence, a global concern, has far reaching consequences for individuals
      and communities. This survey of South African high school students, reported
      baseline prevalence and factors associated with forced sex. Data collected among
      434 adolescents (54.4% boys; 45.6% girls) used a questionnaire developed using
      the I-Change Model conceptual framework. Forced sex prevalence was 14.2% (95% CI
      9.1, 21.5) with a non-significant difference between females (15.0%) and males
      (13.6%) (p = 0.781). After multivariable adjustment, urban location (39%), low
      socio-economic status (15%) and discordant mother/father vital status (20%)
      remained significant risk factors for forced sex. South African high school
      students are still at risk of experiencing forced sex with a higher prevalence in
      females. Interventions to address socio-economic and structural constructs
      contributing to the forced sex prevalence in this population are required.

PMID- 28508135
TI  - Adaptations of archaeal and bacterial membranes to variations in temperature, pH
      and pressure.
AB  - The cytoplasmic membrane of a prokaryotic cell consists of a lipid bilayer or a
      monolayer that shields the cellular content from the environment. In addition,
      the membrane contains proteins that are responsible for transport of proteins and
      metabolites as well as for signalling and energy transduction. Maintenance of the
      functionality of the membrane during changing environmental conditions relies on
      the cell's potential to rapidly adjust the lipid composition of its membrane.
      Despite the fundamental chemical differences between bacterial ester lipids and
      archaeal ether lipids, both types are functional under a wide range of
      environmental conditions. We here provide an overview of archaeal and bacterial
      strategies of changing the lipid compositions of their membranes. Some molecular
      adjustments are unique for archaea or bacteria, whereas others are shared between
      the two domains. Strikingly, shared adjustments were predominantly observed near
      the growth boundaries of bacteria. Here, we demonstrate that the presence of
      membrane spanning ether-lipids and methyl branches shows a striking relationship
      with the growth boundaries of archaea and bacteria.

PMID- 28508139
TI  - Functional annotation of a novel toxin-antitoxin system Xn-RelT of Xenorhabdus
      nematophila; a combined in silico and in vitro approach.
AB  - Toxin-antitoxin (TA) complexes play an important role in stress responses and
      programmed cell death in bacteria. The RelB-RelE toxin antitoxin system is well
      studied in Escherichia coli. In this study, we used combined in silico and in
      vitro approaches to study a novel Xn-RelT toxin from Xenorhabdus nematophila
      bearing its own antitoxin Xn-RelAT-a RelB homolog of E. coli. The structure for
      this toxin-antitoxin pair is yet unknown. We generated homology-based models of
      X. nematophila RelT toxin and antitoxin. The deduced models were further
      characterized for protein-nucleic acid, protein-protein interactions and gene
      ontology. A detrimental effect of recombinant Xn-RelT on host E. coli was
      determined through endogenous toxicity assay. When expressed from a isopropyl
      beta-D-1-thiogalactopyranoside-regulated LacZ promoter, Xn-RelT toxin showed a
      toxic effect on E. coli cells. These observations imply that the conditional
      cooperativity governing the Xn-RelT TA operon in X. nematophila plays an
      important role in stress management and programmed cell death.

PMID- 28508140
TI  - The State and Future of the Primary Care Behavioral Health Model of Service
      Delivery Workforce.
AB  - The growth of the Primary Care Behavioral Health model (PCBH) nationally has
      highlighted and created a workforce development challenge given that most mental
      health professionals are not trained for primary care specialization. This work
      provides a review of the current efforts to retrain mental health professionals
      to fulfill roles as Behavioral Health Consultants (BHCs) including certificate
      programs, technical assistance programs, literature and on-the-job training, as
      well as detail the future needs of the workforce if the model is to sustainably
      proliferate. Eight recommendations are offered including: (1) the development of
      an interprofessional certification body for PCBH training criteria, (2)
      integration of PCBH model specific curricula in graduate studies, (3) integration
      of program development skill building in curricula, (4) efforts to develop
      faculty for PCBH model awareness, (5) intentional efforts to draw students to
      graduate programs for PCBH model training, (6) a national employment
      clearinghouse, (7) efforts to coalesce current knowledge around the provision of
      technical assistance to sites, and (8) workforce specific research efforts.

PMID- 28508141
TI  - Relationships Between Traumatic Life Events, Cognitive Emotion Regulation
      Strategies, and Somatic Complaints.
AB  - The aim of this study was to investigate the relationships between traumatic life
      events, specific cognitive emotion regulation strategies, and present somatic
      complaints. The sample consisted of 465 adults from the general population. The
      participants filled in online self-report questionnaires with regard to somatic
      complaints (SCL-90), cognitive emotion regulation strategies (CERQ) and traumatic
      life events. Multiple regression analysis was performed to study the
      relationships. The results showed that present somatic complaints were
      significantly related to the reporting of past negative events (such as loss and
      maltreatment) that still produce strong and negative feelings in the present.
      Somatic complaints were also significantly related to a more frequent use of
      maladaptive cognitive coping strategies, such as blaming oneself, ruminating, and
      catastrophizing about negative life events. Inquiring about unresolved traumatic
      memories and coping strategies can help guide a clinicians' approach to managing
      patients with somatic complaints that have no clear medical explanation.

PMID- 28508142
TI  - When Is It Better to Wait? Surgical Timing and Recurrence Risk for Children
      Undergoing Repair of Subaortic Stenosis.
AB  - Recurrence of subaortic stenosis (SAS) after surgery is common in children. The
      effects of patient characteristics and surgical timing on disease recurrence are
      largely unknown. We performed a retrospective study, assessing the relative
      effects of patient age and left ventricular outflow tract (LVOT) gradient on the
      need for reoperation for recurrent SAS. We included all children <20 years of age
      who underwent initial surgical resection of SAS at our center, January 2003
      December 2013. Stratified logistic regression was performed, considering the
      effects of patient demographics, clinical characteristics, echocardiographic
      parameters, and operative technique, and clustering standard errors by surgeon.
      The multivariable model was used to simulate predicted probabilities of recurrent
      SAS for children at varying ages and baseline LVOT gradients. Sixty-three
      patients (38 males) underwent initial operation for SAS. Patients were followed
      for a median of 3.7 years (IQR 1.2-7.1). Twenty-one percent of patients (n = 13)
      underwent reoperation for SAS. Twelve were male. For every 10 mmHg increase in
      preoperative peak gradient in boys, the odds of reoperation for SAS doubled (OR
      2.01, CI 1.5-2.72, p < 0.001), and for every additional 6 months of age, the odds
      of reoperation decreased by 14% (OR 0.86, CI 0.84-0.88, p < 0.001). Both younger
      age and higher preoperative outflow tract gradient are independently associated
      with risk of reoperation. Clinicians should consider the age and rate of LVOT
      gradient change-and not just the absolute gradient-in determining initial
      surgical timing.

PMID- 28508143
TI  - Great tit response to decreasing industrial heavy metal emissions.
AB  - This study evaluated the effects of environmental pollution on decreasing great
      tit (Parus major) breeding parameters in an industrial area in the west coast of
      Portugal. Several great tit breeding parameters were monitored in the industrial
      area, as well as in a rural area not affected by industrial emissions. Low levels
      of air pollution in both industrial and rural areas were confirmed by assessing
      trace element concentrations in pine needles. Concentrations of Cd and Hg in pine
      needles from the industrial area (Cd = 0.05 ppm; Hg = 0.005 ppm) were
      significantly lower than those found in needles collected from the reference area
      (Cd = 0.07 ppm; Hg = 0.007 ppm). Additionally, the breeding success of great tits
      increased in the industrial area in comparison to the reference area (0.93 +/-
      0.08 and 0.62 +/- 0.22, respectively). The changes on great tit breeding
      parameters were probably related with changes in the breeding density of other
      competitive species, together with a decreasing frass-fall biomass. Further long
      term ecological studies in industrial areas are necessary to understand the
      changing breeding performance and strategies used by great tits in response to
      pollution shifts in the environment.

PMID- 28508144
TI  - Radical Lymph Node Dissection Along the Proximal Splenic Artery During
      Laparoscopic Gastrectomy for Gastric Cancer Using the Left Lateral Approach.
AB  - BACKGROUND: Recent technical improvements allow safe laparoscopic lymph node
      dissection (LND) in gastric cancer.1 , 2 In suprapancreatic LND, careful LND
      around the celiac artery (CA) is essential. From a patient's right side, deep LND
      is performed around the right side of the CA after dissecting around the common
      hepatic artery (CHA). For LND around the left side of the CA on the same
      operative axis as the right side, we developed a new procedure for LND along the
      proximal splenic artery (SA), performed from the patient's left side. METHODS:
      After LND around the CHA and right side of the CA from the patient's right side,
      the surgeon then moves to the patient's left side. The anterior pancreatic fascia
      is cut at the middle point of the SA to discern the dorsal layer of the LN along
      the SA, such as the splenic vein. LND is performed by preserving the posterior
      pancreatic fascia around the SA in a left-to-right direction. Finally, the LNs
      around the left side of the CA are deeply dissected. RESULTS: We performed this
      procedure on ten patients between April 2016 and January 2017; no operative
      complications were reported in grade II or higher cancer patients.3 After
      exposing the dorsal landmark, LNs around the proximal SA and left side of the CA
      were removed in all patients. CONCLUSION: This procedure enables early
      identification of the dorsal layer and deep LND around the left side of the CA,
      keeping this layer. The left lateral approach is useful for radical LND along the
      proximal SA.

PMID- 28508145
TI  - Sentinel Lymph Node Biopsy for Recurrent Melanoma: A Multicenter Study.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely performed for primary
      cutaneous melanomas; however, limited data exist for SLNB after locally recurrent
      (LR) or in-transit (IT) melanoma. METHODS: Data from three centers performing
      SLNB for LR/IT melanoma (1997 to the present) were reviewed, with the aim of
      assessing (1) success rate; (2) SLNB positivity; and (3) prognostic value of SLNB
      in this population. RESULTS: The study cohort included 107 patients. Management
      of the primary melanoma included prior SLNB for 56 patients (52%), of whom 10
      (18%) were positive and 12 had complete lymph node dissections (CLNDs). In the
      present study, SLNB was performed for IT disease (48/107, 45%) or LR melanoma
      (59/107, 55%). A sentinel lymph node (SLN) was removed in 96% (103/107) of cases.
      Nodes were not removed for four patients due to lymphoscintigraphy failures (2)
      or nodes not found during surgery (2). SLNB was positive in 41 patients (40%, 95%
      confidence interval (CI) 31.5-50.5), of whom 35 (88%) had CLND, with 13 (37%)
      having positive nonsentinel nodes. Median time to disease progression after LR/IT
      metastasis was 1.4 years (95% CI 0.75-2.0) for patients with a positive SLNB, and
      5.9 years (95% CI 1.7-10.2) in SLNB-negative patients (p = 0.18). There was a
      trend towards improved overall survival for patients with a negative SLNB (p =
      0.06). CONCLUSION: SLNB can be successful in patients with LR/IT melanoma, even
      if prior SLNB was performed. In this population, the rates of SLNB positivity and
      nonsentinel node metastases were 40% and 37%, respectively. SLNB may guide
      management and prognosis after LR/IT disease.

PMID- 28508146
TI  - Laparoscopic Parenchymal-Sparing Liver Resections Using the Intrahepatic
      Glissonian Approach.
AB  - BACKGROUND: One of the main criticisms of laparoscopic liver resection is that it
      is difficult, or not possible, to perform liver-sparing resections. Our aim was
      to present short videos where the intrahepatic Glissonian approach was used to
      perform anatomical liver segmental resections, instead of a larger operation, to
      avoid unnecessary sacrifice of the liver parenchyma. METHODS: We selected six
      types of anatomical liver resections to exemplify the use of the intrahepatic
      Glissonian approach to perform segment-oriented liver resections. These types of
      hepatectomies were used as an alternative to right or left hepatectomy, or as an
      alternative to extended liver resections. RESULTS: The intrahepatic Glissonian
      approach was feasible in all cases. The use of anatomical landmarks previously
      described was essential to reach and control the Glissonian pedicles. Among the
      liver-sparing resections, we were able to perform right anterior (S5 + S8) and
      posterior (S6 + S7) sectionectomies, resection of segments 2, 3, and 4, and
      mesohepatectomy (S4 + S5 + S8). No patient presented postoperative liver failure.
      CONCLUSIONS: Laparoscopic liver-sparing resections are feasible and may be a good
      alternative to hemihepatectomies or extended liver resections. The use of the
      intrahepatic Glissonian approach can be useful.

PMID- 28508147
TI  - Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human
      Pathogenic Bacteria using a Computational Search Approach.
AB  - A systematic analysis of beta-lactamases based on comparative proteomics has not
      been performed thus far. In this report, we searched for the presence of beta
      lactam-related proteins in 591 bacterial proteomes belonging to 52 species that
      are pathogenic to humans. The amino acid sequences for 19 different types of beta
      lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP,
      OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and
      were used to construct 19 HMM profiles, which were used to identify potential
      beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877
      matches that included the word "beta-lactamase" and/or "penicillin" in the
      functional annotation and/or in any of its regions were obtained. These enzymes
      were mainly described as "penicillin-binding proteins," "beta-lactamases," and
      "metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In
      addition, proteins classified as "beta-lactamases" were observed in 39 of the
      species included. A positive correlation between the number of beta-lactam
      related proteins per species and the proteome size was observed (R 0.78, P <
      0.00001). This correlation partially explains the high presence of beta-lactam
      related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus
      anthracis, and Mycobacterium tuberculosis, along with their absence in small
      proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types
      of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in
      particular species that corresponded with those reported in the literature. We
      additionally detected other potential species-specific beta-lactamases that have
      not yet been reported. In the future, better results will be achieved due to more
      accurate sequence annotations and a greater number of sequenced genomes.

PMID- 28508148
TI  - Thermographic skin temperature measurement compared with cold sensation in
      predicting the efficacy and distribution of epidural anesthesia.
AB  - Due to the high rates of epidural failure (3-32%), novel techniques are required
      to objectively assess the successfulness of an epidural block. In this study we
      therefore investigated whether thermographic temperature measurements have a
      higher predictive value for a successful epidural block when compared to the cold
      sensation test as gold standard. Epidural anesthesia was induced in 61 patients
      undergoing elective abdominal, thoracic or orthopedic surgery. A thermographic
      picture was recorded at 5, 10 and 15 min following epidural anesthesia induction.
      After 15 min a cold sensation test was performed. Epidural anesthesia is
      associated with a decrease in skin temperature. Thermography predicts a
      successful epidural block with a sensitivity of 54% and a PPV of 92% and a
      specificity of 67% and a NPV of 17%. The cold sensation test shows a higher
      sensitivity and PPV than thermography (97 and 93%), but a lower specificity and
      NPV than thermography (25 and 50%). Thermographic temperature measurements can be
      used as an additional and objective method for the assessment of the
      effectiveness of an epidural block next to the cold sensation test, but have a
      low sensitivity and negative predictive value. The local decrease in temperature
      as observed in our study during epidural anesthesia is mainly attributed to a
      core-to-peripheral redistribution of body heat and vasodilation.

PMID- 28508149
TI  - Parkinson's Disease-Associated Mutant LRRK2-Mediated Inhibition of miRNA Activity
      is Antagonized by TRIM32.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder.
      Accumulating evidences suggest that PD might have a strong neurodevelopmental
      component. Among the genetic cases, mutations in the leucine-rich repeat kinase 2
      (LRRK2) are well known to be disease causing. Although the molecular mechanism of
      the pathogenic LRRK2 function is not fully clear, inhibition of microRNA (miRNA)
      activity has been suggested to be among the pathogenic LRRK2 targets. Here, we
      demonstrate that the miRNA activity inhibition function of pathogenic LRRK2 is
      directly antagonized by the neuronal cell fate determinant TRIM32. These findings
      suggest that TRIM32 might be a modifier for PD and could be a novel therapeutic
      target.

PMID- 28508150
TI  - Exogenous BDNF Increases Mitochondrial pCREB and Alleviates Neuronal Metabolic
      Defects Following Mechanical Injury in a MPTP-Dependent Way.
AB  - Metabolic defects are common pathological phenomena following traumatic brain
      injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic
      factor (BDNF) is an important regulator of neuronal survival, development,
      function, and plasticity. This study was designed to investigate the potential
      effects of BDNF on TBI-induced metabolic defects and their underlying molecular
      mechanisms. BDNF was added into cultured neurons to a concentration of 25, 50,
      and 100 ng/ml, respectively, right after mechanical injury and metabolite levels
      were analyzed 4 h post injury. The mitochondrial phosphorylated cAMP response
      element-binding protein (pCREB) distribution and complex V synthesis, as well as
      their roles in metabolic defects, were evaluated. We found that exogenous BDNF
      improved metabolic defects, especially the uncoupling of oxidative
      phosphorylation. BDNF increased pCREB in mitochondrial inner membrane and matrix
      and promoted mitochondrial complex V synthesis. We also found that these results
      were negatively regulated by the mitochondrial permeability transition pore
      (MPTP) antagonist CsA and positively regulated by the MPTP agonist atractyloside.
      BDNF's protectional effects on metabolic defects were abolished by CREB knockout.
      When administrated in a dominant interfering CREB mutant (A-CREB) model,
      mitochondrial pCREB accumulation could still be observed, but the synthesis of
      complex V and alleviation of metabolic defects were repressed. Our data
      demonstrate that exogenous BDNF mitigates neuronal metabolic defects following
      mechanical injury by promoting the pCREB accumulation in mitochondrial inner
      membrane and matrix, which is regulated by MPTP opening, thus facilitating the
      synthesis of mitochondrial complex V.

PMID- 28508151
TI  - Tunable and Nontoxic Fluorescent Probes Based on Carbon Dots for Imaging of
      Indole Propionic Acid Receptor in Plant Tissues in Situ.
AB  - Indole propionic acid (IPA) is one of the important plant growth hormones for
      promoting rooting and fruiting. Labeling IPA receptor in plant tissues is able to
      further track the signal transduction processes of IPA and uncover the function
      mechanism of IPA on crop productions. In this paper, a tunable and nontoxic
      fluorescent probe for IPA receptors was designed and synthetized base on carbon
      dots (C dots). Firstly carboxyl-modified carbon dots were prepared by high
      temperature cracking of citric acid. The fluorescence emission wavelengths of C
      dots varied with the excitation wavelengths change. Then IPA-modified carbon dots
      (IPA-C dots) were prepared by coupling the amino of tryptophan with the carboxyl
      of as-prepared carbon dots. Compared with C dots, the fluorescence intensity of
      IPA-C dots was double and the fluorescence stability was satisfactory under
      various conditions. This probe retained the biological activity of IPA and acted
      as target recognition of IPA receptors in plant tissues. The probe could avoid
      green fluorescence background of plants. The imaging results showed that the IPA
      receptors mainly existed on the membrane of stele. The toxicity test indicated
      the probe was less toxic than traditional inorganic semiconductor quantum dots.

PMID- 28508152
TI  - Detection of HER2 Amplification in Circulating Tumor Cells of HER2-Negative
      Gastric Cancer Patients.
AB  - A key to the successful use of targeted cancer therapy is the ability to
      preselect patients who are likely to benefit from the treatment according to
      molecular markers. Assessment for predicting therapy response is mostly done
      using tumor biopsies. However, these might not truly represent all of the
      patient's malignant cells because of tumor heterogeneity and/or clonal evolution
      during disease progression. One potential strategy that can complement primary
      tumor biopsy is the analysis of circulating tumor cells (CTCs). In this study, we
      analyzed CTCs of patients with gastric cancer (GC) to find those who were likely
      to benefit from trastuzumab therapies. We developed an imaging-based method that
      enabled CTC identification simultaneously with evaluation of HER2 gene
      amplification (the 3D-IF-FISH method). Then we performed a study enrolling 101 GC
      patients in whom we analyzed CTCs by both 3D-IF-FISH and an FDA-approved
      CellSearch system. As compared with the CellSearch system, 3D-IF-FISH methods
      identified a higher number of patients whose primary tumors were HER2- but who
      had HER2+ CTCs, suggesting that the 3D-IF-FISH method is effective in
      preselecting patients for trastuzumab therapies. To demonstrate this, we
      performed an exploratory clinical study to evaluate the clinical benefits of
      trastuzumab treatment for advanced GC patients (n = 15) whose primary tumors were
      HER2-, but whose CTCs showed HER2 amplification. An interim evaluation after the
      first stage showed that these preselected patients had response rates comparable
      to those reported in the trastuzumab-plus-chemotherapy arm of the ToGA study. The
      present study offers a new, non-invasive strategy to select patients who are
      likely to benefit from trastuzumab-based therapies, despite their primary biopsy
      being HER2-negative. (UMIN ID: UMIN000008622).

PMID- 28508154
TI  - Estimating Loss of Brucella Abortus Antibodies from Age-Specific Serological Data
      In Elk.
AB  - Serological data are one of the primary sources of information for disease
      monitoring in wildlife. However, the duration of the seropositive status of
      exposed individuals is almost always unknown for many free-ranging host species.
      Directly estimating rates of antibody loss typically requires difficult
      longitudinal sampling of individuals following seroconversion. Instead, we
      propose a Bayesian statistical approach linking age and serological data to a
      mechanistic epidemiological model to infer brucellosis infection, the probability
      of antibody loss, and recovery rates of elk (Cervus canadensis) in the Greater
      Yellowstone Ecosystem. We found that seroprevalence declined above the age of
      ten, with no evidence of disease-induced mortality. The probability of antibody
      loss was estimated to be 0.70 per year after a five-year period of seropositivity
      and the basic reproduction number for brucellosis to 2.13. Our results suggest
      that individuals are unlikely to become re-infected because models with this
      mechanism were unable to reproduce a significant decline in seroprevalence in
      older individuals. This study highlights the possible implications of antibody
      loss, which could bias our estimation of critical epidemiological parameters for
      wildlife disease management based on serological data.

PMID- 28508153
TI  - Cellular and molecular perspectives in rheumatoid arthritis.
AB  - Synovial immunopathology in rheumatoid arthritis is complex involving both
      resident and infiltrating cells. The synovial tissue undergoes significant
      neovascularization, facilitating an influx of lymphocytes and monocytes that
      transform a typically acellular loose areolar membrane into an invasive tumour
      like pannus. The microvasculature proliferates to form straight regularly
      branching vessels; however, they are highly dysfunctional resulting in reduced
      oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid
      factor and anti-citrullinated protein antibodies are found at an early stage,
      often before arthritis has developed, and they have been implicated in the
      pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction
      thus ensue and, in turn, through the increased production of reactive oxygen
      species actively induce inflammation. Key pro-inflammatory cytokines, chemokines
      and growth factors and their signalling pathways, including nuclear factor
      kappaB, Janus kinase-signal transducer, are highly activated when immune cells
      are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival
      reactions by activating. This review attempts to highlight those aberrations in
      the innate and adaptive immune systems including the role of genetic and
      environmental factors, autoantibodies, cellular alterations, signalling pathways
      and metabolism that are implicated in the pathogenesis of RA and may therefore
      provide an opportunity for therapeutic intervention.

PMID- 28508156
TI  - Pulse wave velocity measurement as a marker of arterial stiffness in pediatric
      inflammatory bowel disease: a pilot study.
AB  - : In adults with inflammatory bowel disease (IBD), the incidence of
      cardiovascular events is increased, leading to long-term morbidity. Arterial
      stiffness (AS) measured by pulse wave velocity (PWV) is a validated early
      precursor of cardiovascular disease (CVD), and measurement of PWV was shown to be
      a feasible test in children. The aim of this study was to assess AS in children
      with IBD. In this prospective study, we determined PWV between the carotid and
      femoral artery (PWVcf) in 25 children and adolescents with IBD (11 females,
      median age 14.1 years, median disease duration 2.8 years). The majority (68%) of
      the subjects were in clinical remission, and 48% received anti-tumor necrosis
      factor alpha (TNFalpha) treatment. AS was not increased in this cohort of
      children and adolescents with IBD, who did not have signs of cardiovascular
      disease, such as arterial hypertension. CONCLUSION: PWV seems to be normal in
      children with IBD in remission or with mild disease activity. Larger studies
      should assess its potential role as a valid and non-invasive follow-up marker in
      children with IBD, to avoid cardiovascular complications. What is Known : *
      Inflammatory bowel disease (IBD) is a risk factor of cardiovascular disease
      (CVD). * Pulse wave velocity (PWV) measurement is the current gold standard to
      assess arterial stiffness (AS), which is an early predictor of CVD. What is New:
      * This is the first study using PWV measurements to determine AS in children with
      IBD. * In children with IBD in remission or only mild disease activity AS is not
      increased.

PMID- 28508155
TI  - Retention of South African Adolescents in a 54-Month Longitudinal HIV Risk
      Reduction Trial.
AB  - Retention of participants in clinical trials is a central concern of HIV/STI
      behavioral researchers and research sponsors. This article describes the
      strategies used for addressing the challenges in retaining South African
      adolescents for a 54-month longitudinal study. The objective of the South African
      adolescent health promotion long-term follow-up trial was to test the
      sustainability of the effects of an HIV/STI risk reduction intervention, "Let Us
      Protect Our Future," on young adolescents as they aged into middle and late
      adolescence. Inaccurate contact information, invalid mobile telephone numbers,
      lack of transportation, transitory family addresses, and family relocation were
      among the challenges to retaining participants. Despite a significant gap in time
      of 36 months between the main trial and the long-term follow-up study, 99.2% of
      1057 participants were retained. Solutions used for retaining the adolescents are
      discussed with suggestions offered for retaining adolescents in longitudinal
      HIV/STI prevention clinical trials in low resource countries.

PMID- 28508157
TI  - Integument cell gelatinisation-the fate of the integumentary cells in Hieracium
      and Pilosella (Asteraceae).
AB  - Members of the genera Hieracium and Pilosella are model plants that are used to
      study the mechanisms of apomixis. In order to have a proper understanding of
      apomixis, knowledge about the relationship between the maternal tissue and the
      gametophyte is needed. In the genus Pilosella, previous authors have described
      the specific process of the "liquefaction" of the integument cells that surround
      the embryo sac. However, these observations were based on data only at the light
      microscopy level. The main aim of our paper was to investigate the changes in the
      integument cells at the ultrastructural level in Pilosella officinarum and
      Hieracium alpinum. We found that the integument peri-endothelial zone in both
      species consisted of mucilage cells. The mucilage was deposited as a thick layer
      between the plasma membrane and the cell wall. The mucilage pushed the protoplast
      to the centre of the cell, and cytoplasmic bridges connected the protoplast to
      the plasmodesmata through the mucilage layers. Moreover, an elongation of the
      plasmodesmata was observed in the mucilage cells. The protoplasts had an
      irregular shape and were finally degenerated. After the cell wall breakdown of
      the mucilage cells, lysigenous cavities that were filled with mucilage were
      formed.

PMID- 28508158
TI  - How I do it: surgical ligation of craniocervical junction dural AV fistulas.
AB  - BACKGROUND: Dural arteriovenous fistulas (DAVFs) of the craniocervical junction
      are uncommon vascular lesions, which often require surgical treatment even in the
      endovascular era. METHODS: Most commonly, the fistula is placed laterally, and
      surgical ligation is performed through a lateral suboccipital craniotomy. After
      dural opening, the area is inspected, and the arterialized vein is identified
      emerging from the dura, often adjacent to the entry point of the vertebral
      artery, and ligated. CONCLUSIONS: A far lateral craniotomy is the authors'
      preferred surgical approach for accessing and treating dural arteriovenous
      fistulas of the craniocervical junction that cannot be reached endovascularly.

PMID- 28508159
TI  - Constant dripping wears away the bone: intraosseous C2 and suboccipital
      intradiploic cerebrospinal fluid collection after Chiari I decompressive surgery.
AB  - The objective of decompressive surgery for Chiari I malformation is to create
      additional space to accommodate the ectopic cerebellar tonsils and to improve the
      flow of cerebrospinal fluid. To the best of our knowledge, we report the first
      case of a patient with previous Chiari I decompression presenting 5 years after
      surgery at the same time as an intraosseous C2 and a suboccipital intradiploic
      cerebrospinal fluid accumulation. Because of the progressive nature of the C2
      cerebrospinal fluid collection causing bone destruction, surgical management was
      indicated. To avoid the erosion of the bone, we propose that the iatrogenic
      exposure of the diploe and the vertebral spongiosa that may come into contact
      with the cerebrospinal fluid should be sealed off with bone wax or a similar
      material.

PMID- 28508160
TI  - Operative simulation of anterior clinoidectomy using a rapid prototyping model
      molded by a three-dimensional printer.
AB  - BACKGROUND: As the anatomical three-dimensional (3D) positional relationship
      around the anterior clinoid process (ACP) is complex, experience of many
      surgeries is necessary to understand anterior clinoidectomy (AC). We prepared a
      3D synthetic image from computed tomographic angiography (CTA) and magnetic
      resonance imaging (MRI) data and a rapid prototyping (RP) model from the imaging
      data using a 3D printer. The objective of this study was to evaluate anatomical
      reproduction of the 3D synthetic image and intraosseous region after AC in the RP
      model. In addition, the usefulness of the RP model for operative simulation was
      investigated. METHODS: The subjects were 51 patients who were examined by CTA and
      MRI before surgery. The size of the ACP, thickness and length of the optic nerve
      and artery, and intraosseous length after AC were measured in the 3D synthetic
      image and RP model, and reproducibility in the RP model was evaluated. In
      addition, 10 neurosurgeons performed AC in the completed RP models to investigate
      their usefulness for operative simulation. RESULTS: The RP model reproduced the
      region in the vicinity of the ACP in the 3D synthetic image, including the
      intraosseous region, at a high accuracy. In addition, drilling of the RP model
      was a useful operative simulation method of AC. CONCLUSIONS: The RP model of the
      vicinity of ACP, prepared using a 3D printer, showed favorable anatomical
      reproducibility, including reproduction of the intraosseous region. In addition,
      it was concluded that this RP model is useful as a surgical education tool for
      drilling.

PMID- 28508162
TI  - First report of oestrosis in aoudad from southeastern Spain.
AB  - In spring 2016, we analyzed the skull of 44 aoudads (Ammotragus lervia) from
      Sierra Espuna Regional Park (SE Spain) for the presence of oestrid larvae.
      Oestrus ovis larvae were found in 27.3% of sampled hosts, with a mean intensity
      of 1.5 +/- 6.1 larvae/per parasitized host (range 1-21). To our knowledge, this
      is the first report of oestrosis affecting this host species.

PMID- 28508163
TI  - Development of molecular diagnostic protocols for detecting three types of
      Entamoeba from diarrheal and asymptomatic pigs and environmental moist soils.
AB  - Entamoeba suis and Entamoeba polecki subtypes (ST) 1 and 3 have recently been
      implicated in disease outbreaks in pigs. However, the distributions of these
      parasites in Japan and the potential sources of infection on farms still remain
      unclear. Here, we examined a farm of fattening/growing pigs with abnormal feces
      in Kagoshima Prefecture, Japan, and found the presence of parasites in the farm
      environment. Examination of intestinal tissues from pigs presenting with
      ulcerative colitis revealed a large number of trophozoites that had invaded the
      lesions. We identified single and mixed infections of E. suis and E. polecki ST1
      and ST3 in paraffin sections or fecal samples from affected pigs. Two subtypes of
      Entamoeba were identified using four primer sets by PCR and sequencing. The
      parasites were detected in moist soil samples obtained around the drinking water
      source or puddles, implicating transmission of cysts via contaminated soils.
      Additionally, we found evidence of Entamoeba spp. and coinfections in surveyed
      pigs without any diarrhea at two neighboring farms. Our results establish methods
      for successfully identification of parasites, including cases in which multiple
      infections are present.

PMID- 28508164
TI  - Viability of Strongyloides venezuelensis eggs and larvae in vermiculite
      containing the fungus Duddingtonia flagrans.
AB  - Strongyloidiasis is the most clinically important disease among the infections
      caused by geohelminths, seeing that this parasite can cause autoinfection. The
      use of nematophagous fungi like Duddingtonia flagrans, that have predation action
      on eggs and infecciososas forms of helminths, emerges as an alternative method
      for environmental control. For this reason, analyzing the viability of larvae and
      eggs of Strongyloides venezuelensis and the action of Duddingtonia flagrans AC001
      in vermiculite, as well as the action of the nematophagous fungi in different
      growth stages, is important to elaborate and define the best culture conditions
      that favor the activity of the fungus. Two different growth conditions were
      applied: both eggs and AC001 fungi were added at the same time to the vermiculite
      (assay A) and the addition of eggs after the growth of the AC001 fungi in the
      vermiculite (assay B). To recover the L3 larvae, the Baermann-Moraes method was
      applied, followed by the counting of L3 dead and alive. At last, it was observed
      that the vermiculite enriched with organic material is an adequate culture medium
      not only for the growth of the S. venezuelensis but also for the growth of the D.
      flagrans fungus, being therefore, a satisfactory culture medium for tests of
      viability and predatory action of this fungus. It was also observed that the
      activity of the AC001 fungus is greater when it is growing concomitantly with the
      eggs, in other words, when it is in the adaptation phase.

PMID- 28508165
TI  - Frequency of Toxoplasma gondii in the retina in eye banks in Brazil.
AB  - Ocular toxoplasmosis is the main cause of posterior uveitis worldwide frequently
      leading to vision loss. In Brazil, the seroprevalence of Toxoplasma gondii
      infection ranges from 50 to 80% depending of the region studied. The frequency of
      toxoplasmic retinal scar may reach 18% of the adults in the South of Brazil. Our
      goal was to determine the frequency of T. gondii DNA in retinas from eye banks
      from different regions in Brazil. A total of 162 eyes were obtained from eye
      banks in Manaus (n = 60), Sao Paulo (n = 60), Chapeco (n = 26), and Joinville (n
      = 16). The retinas were macroscopically analyzed and collected for DNA
      extraction. Real-time PCR (qPCR) was performed using the T. gondii B1 marker. By
      qPCR, a higher frequency of T. gondii DNA in the retinas from the eye bank of
      Joinville (25%) was found when compared to Manaus (5%). The retinas from Sao
      Paulo and Chapeco were qPCR negative. Clinical examination determined the retina
      lesions to be compatible with toxoplasmosis in the following frequencies:
      Joinville (62.5%), Manaus (10%), Sao Paulo (6.7%), and Chapeco (15.4%).

PMID- 28508166
TI  - Toxoplasma gondii and schizophrenia: a review of published RCTs.
AB  - Over the last 60 years, accumulating evidence has suggested that acute, chronic,
      and maternal Toxoplasma gondii infections predispose to schizophrenia. More
      recent evidence suggests that chronically infected patients with schizophrenia
      present with more severe disease. After acute infection, parasites form walled
      cysts in the brain, leading to lifelong chronic infection and drug resistance to
      commonly used antiparasitics. Chronic infection is the most studied and closely
      linked with development and severity of schizophrenia. There are currently four
      published randomized controlled trials evaluating antiparasitic drugs,
      specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients
      with schizophrenia. No trials have demonstrated a change in psychopathology with
      adjunctive treatment. Published trials have either selected drugs without
      evidence against chronic infection or used them at doses too low to reduce brain
      cyst burden. Furthermore, trials have failed to achieve sufficient power or
      account for confounders such as previous antipsychotic treatment, sex, age, or
      rhesus status on antiparasitic effect. There are currently no ongoing trials of
      anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify
      further testing.

PMID- 28508167
TI  - Lessons from a 15-year-old boy with advanced schistosomiasis japonica in China: a
      case report.
AB  - Schistosomiasis is a chronic, parasitic disease caused by flukes (trematodes) of
      the genus Schistosoma, which presents the most important global burden of the 17
      neglected tropical diseases listed by the World Health Organization. China has
      made great achievements in schistosomiasis control, and now China is planning to
      move forward, to eliminate schistosomiasis within 2020, but the fact cannot be
      denied that the possibility of schistosome infection is still there in some
      endemic due to its zoonotic nature as well as wide distribution of its
      intermediate hosts (snails). Thus, how to interrupt the transmission in areas
      with distribution of schistosomes and intermediate snails becomes a very serious
      challenge that China is facing. In this paper, it is reported an advanced
      schistosomiasis japonica case of a 15-year-old boy which is extremely rare in the
      current schistosomiasis control in China. Thus, it is supposed to strengthen
      health education of school children and to train professional physicians of local
      hospitals.

PMID- 28508169
TI  - Variation in the relationship between birth weight and subsequent obesity by
      household income.
AB  - There is evidence to suggest that high birth weight increases subsequent BMI.
      However, little attention has been paid to variations in this impact between
      population groups. This study investigates the relationship between high birth
      weight and subsequent obesity, and whether or not this relationship varies by
      household income. Data was taken from fourteen rounds of the Health Survey for
      England (between 2000-2014; N = 31,043) for children aged 2-16. We regressed
      obesity in childhood against birth weight, accounting for interactions between
      birth weight and household income, using sibling-fixed effects models. High birth
      weight was associated with increased risk of subsequent obesity. This association
      was significantly more pronounced in children from low-income families, compared
      with children from high-income families. A 1 kg increase in birth weight
      increased the probability of obesity by 7% in the lowest income tertile and 4% in
      the highest income tertile. This suggests that early socioeconomic deprivation
      compound the effect of high birth weight on obesity.

PMID- 28508168
TI  - Distinct Histone Modifications Modulate DEFB1 Expression in Human Vaginal
      Keratinocytes in Response to Lactobacillus spp.
AB  - Vaginal commensal lactobacilli are considered to contribute significantly to the
      control of vaginal microbiota by competing with other microflora for adherence to
      the vaginal epithelium and by producing antimicrobial compounds. However, the
      molecular mechanisms of symbiotic prokaryotic-eukaryotic communication in the
      vaginal ecosystem remain poorly understood. Here, we showed that both DNA
      methylation and histone modifications were associated with expression of the
      DEFB1 gene, which encodes the antimicrobial peptide human beta-defensin-1, in
      vaginal keratinocyte VK2/E6E7 cells. We investigated whether exposure to
      Lactobacillus gasseri and Lactobacillus reuteri would trigger the epigenetic
      modulation of DEFB1 expression in VK2/E6E7 cells in a bacterial species-dependent
      manner. While enhanced expression of DEFB1 was observed when VK2/E6E7 cells were
      exposed to L. gasseri, treatment with L. reuteri resulted in reduced DEFB1
      expression. Moreover, L. gasseri stimulated the recruitment of active histone
      marks and, in contrast, L. reuteri led to the decrease of active histone marks at
      the DEFB1 promoter. It was remarkable that distinct histone modifications within
      the same promoter region of DEFB1 were mediated by L. gasseri and L. reuteri.
      Therefore, our study suggested that one of the underlying mechanisms of DEFB1
      expression in the vaginal ecosystem might be associated with the epigenetic
      crosstalk between individual Lactobacillus spp. and vaginal keratinocytes.

PMID- 28508170
TI  - Viral Vector-Based Evaluation of Regulatory Regions in the Neuron-Specific
      Enolase (NSE) Promoter in Mouse Cerebellum In Vivo.
AB  - We investigated the neuron-specific enolase (NSE) promoter in terms of its
      promoter strength and neuronal specificity in the cerebellum in vivo. The 1.8 kb
      rat NSE promoter was divided into three regions, A (0.8 kb), B (0.7 kb), and C
      (0.3 kb), starting from the 5' side. Then, we made various deletion constructs
      and assessed them by virally expressing GFP under the control of one of the
      deleted promoters. Removing region A reduced GFP expression to ~6% of that of the
      original 1.8 kb promoter. Further deletion of region B (presence of region C
      alone) did not influence the promoter strength, but removing region B from the
      original 1.8 kb promoter reduced the GFP expression to ~6% of the original level,
      similar to the level observed after deletion of region A. Immunohistochemistry
      showed robust GFP expression in Purkinje cells and modest expression in
      interneurons by the original promoter. Removing region A and/or region B
      abolished the GFP expression in Purkinje cells in most cerebellar lobules, with
      the expression in interneurons almost unchanged. These results suggest that
      region C, which is a proximal 0.3 kb sequence, contains cis-acting elements that
      drive transcription predominantly in interneurons. The addition of either region
      A or B onto region C does not alter the promoter properties; however, the
      addition of both regions A and B to region C drastically enhanced the promoter
      activity in Purkinje cells, suggesting the synergistic action of cis-acting
      regulatory elements in regions A and B for strong activation in Purkinje cells.

PMID- 28508171
TI  - Over-expression of tobacco UBC1 encoding a ubiquitin-conjugating enzyme increases
      cadmium tolerance by activating the 20S/26S proteasome and by decreasing Cd
      accumulation and oxidative stress in tobacco (Nicotiana tabacum).
AB  - Ubiquitin (Ub)-conjugating enzyme (UBC, E2) receives Ub from Ub-activating enzyme
      (E1) and transfers it to target proteins, thereby playing a key role in Ub/26S
      proteasome-dependent proteolysis. UBC has been reported to be involved in
      tolerating abiotic stress in plants, including drought, salt, osmotic and water
      stresses. To isolate the genes involved in Cd tolerance, we transformed WT (wild
      type) yeast Y800 with a tobacco cDNA expression library and isolated a tobacco
      cDNA, NtUBC1 (Ub-conjugating enzyme), that enhances cadmium tolerance. When
      NtUBC1 was over-expressed in tobacco, cadmium tolerance was enhanced, but the Cd
      level was decreased. Interestingly, 20S proteasome activity was increased and
      ubiquitinated protein levels were diminished in response to cadmium in NtUBC1
      tobacco. By contrast, proteasome activity was decreased and ubiquitinated protein
      levels were slightly enhanced by Cd treatment in control tobacco, which is
      sensitive to Cd. Moreover, the oxidative stress level was induced to a lesser
      extent by Cd in NtUBC1 tobacco compared with control plants, which is ascribed to
      the higher activity of antioxidant enzymes in NtUBC1 tobacco. In addition, NtUBC1
      tobacco displayed a reduced accumulation of Cd compared with the control, likely
      due to the higher expression of CAX3 (Ca2+/H+ exchanger) and the lower expression
      of IRT1 (iron-responsive transporter 1) and HMA-A and -B (heavy metal ATPase). In
      contrast, atubc1 and atubc1atubc2 Arabidopsis exhibited lower Cd tolerance and
      proteasome activity than WT. In conclusion, NtUBC1 expression promotes cadmium
      tolerance likely by removing cadmium-damaged proteins via Ub/26S proteasome
      dependent proteolysis or the Ub-independent 20S proteasome and by diminishing
      oxidative stress through the activation of antioxidant enzymes and decreasing Cd
      accumulation due to higher CAX3 and lower IRT1 and HMA-A/B expression in response
      to 50 uM Cd challenge for 3 weeks.

PMID- 28508172
TI  - Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in
      Rats.
AB  - Spinal cord injury (SCI) is a complex debilitating condition leading to permanent
      life-long neurological deficits. The complexity of SCI suggests that a concerted
      multi-targeted therapeutic approach is warranted to optimally improve function.
      Damage to spinal cord is complicated by an increased detrimental response from
      secondary injury factors mediated by activated glial cells and infiltrating
      macrophages. While elevation of enolase especially neuron specific enolase (NSE)
      in glial and neuronal cells is believed to trigger inflammatory cascades in acute
      SCI, alteration of NSE and its subsequent effects in acute SCI remains unknown.
      This study measured NSE expression levels and key inflammatory mediators after
      acute SCI and investigated the role of ENOblock, a novel small molecule inhibitor
      of enolase, in a male Sprague-Dawley (SD) rat SCI model. Serum NSE levels as well
      as cytokines/chemokines and metabolic factors were evaluated in injured animals
      following treatment with vehicle alone or ENOblock using Discovery assay. Spinal
      cord samples were also analyzed for NSE and MMPs 2 and 9 as well as glial markers
      by Western blotting. The results indicated a significant decrease in serum
      inflammatory cytokines/chemokines and NSE, alterations of metabolic factors and
      expression of MMPs in spinal cord tissues after treatment with ENOblock (100
      ug/kg, twice). These results support the hypothesis that activation of glial
      cells and inflammation status can be modulated by regulation of NSE expression
      and activity. Analysis of SCI tissue samples by immunohistochemistry confirmed
      that ENOblock decreased gliosis which may have occurred through reduction of
      elevated NSE in rats. Overall, elevation of NSE is deleterious as it promotes
      extracellular degradation and production of inflammatory cytokines/chemokines and
      metabolic factors which activates glia and damages neurons. Thus, reduction of
      NSE by ENOblock may have potential therapeutic implications in acute SCI.

PMID- 28508173
TI  - Neuroprotective Effects of Lycium barbarum Polysaccharide on Focal Cerebral
      Ischemic Injury in Mice.
AB  - Increasing evidence demonstrates inflammation contributes to neuronal death
      following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been
      reported to prevent scopolamine-induced cognitive and memory deficits. We
      recently indicated that LBP exerts neuroprotective effect against focal cerebral
      ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The
      aim of this study was to investigate the neuroprotective effects of LBP against
      the behavioral dysfunction induced by focal cerebral ischemia injury in mice.
      Following 7 successive days of pretreatment with LBP (10, 20 and 40 mg/kg) and
      nimodipine (4 mg/kg) by intragastric gavage, mice were subjected to middle
      cerebral artery occlusion (MCAO). Following reperfusion, cerebral blood flows,
      the total power of the spontaneous EEG, and morphological changes were estimated.
      Learning and memory ability, and motor coordination were determined by Morris
      water maze task, rotarod and grip test. Western blot analysis, Real-Time
      fluorogenic PCR assays, and immunofluorescence staining were used to examine the
      expression of proinflammatory mediators and activation of microglia. The present
      study showed that LBP pretreatment significantly enhanced regional cortical blood
      flow and the total power of the spontaneous EEG, improved memory and motor
      coordination impairments, and inhibited over-activation of microglia and
      astrocytes after MCAO. Further study demonstrated LBP suppressed MCAO-induced
      activations of P65 NF-kappaB and P38 MAPK, and prevented up-regulations of
      proinflammatory mediators in hippocampus. Our data suggest that LBP can exert
      functional recovery of memory and motor coordination deficits and neuroprotective
      effect against cerebral ischemic injury in mice.

PMID- 28508175
TI  - Comparison of R-CVP with R-CHOP for very elderly patients aged 80 or over with
      diffuse large B cell lymphoma.

PMID- 28508174
TI  - Preclinical Comparison of Mechanistically Different Antiseizure, Antinociceptive,
      and/or Antidepressant Drugs in a Battery of Rodent Models of Nociceptive and
      Neuropathic Pain.
AB  - The series of experiments herein evaluated prototype drugs representing different
      mechanisms of antiseizure, antinociceptive or antidepressant action in a battery
      of preclinical pain models in adult male CF#1 mice (formalin, writhing, and tail
      flick) and Sprague Dawley rats partial sciatic nerve ligation (PSNL). In the
      formalin assay, phenytoin (PHT, 6 mg/kg), sodium valproate (VPA, 300 mg/kg),
      amitriptyline (AMI, 7.5 and 15 mg/kg), gabapentin (GBP, 30 and 70 mg/kg),
      tiagabine (TGB, 5 and 15 mg/kg), and acetominophen (APAP, 250 and 500 mg/kg)
      reduced both phases of the formalin response to <= 25% of vehicle-treated mice.
      In the acetic acid induced writhing assay, VPA (300 mg/kg), ethosuximide (ETX,
      300 mg/kg), morphine (MOR, 5 & 10 mg/kg), GBP (10, 30, and 60 mg/kg), TGB (15
      mg/kg), levetiracetam (LEV, 300 mg/kg), felbamate (FBM, 80 mg/kg) and APAP (250
      mg/kg) reduced writhing to <= 25% of vehicle-treated mice. In the tail flick
      test, MOR (1.25-5 mg/kg), AMI (15 mg/kg) and TGB (5 mg/kg) demonstrated
      significant antinociceptive effects. Finally, carbamazepine (CBZ, 20 and 50
      mg/kg), VPA, MOR (2 and 4 mg/kg), AMI (12 mg/kg), TPM (100 mg/kg), lamotrigine
      (LTG, 40 mg/kg), GBP (60 mg/kg), TGB (15 mg/kg), FBM (35 mg/kg), and APAP (250
      mg/kg) were effective in the PSNL model. Thus, TGB was the only prototype
      compound with significant analgesic effects in each of the four models, while
      AMI, GBP, APAP, and MOR each improved three of the four pain phenotypes. This
      study highlights the importance evaluating novel targets in a variety of pain
      phenotypes.

PMID- 28508176
TI  - The prognostic role of CD68 and FoxP3 expression in patients with primary central
      nervous system lymphoma.
AB  - The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma
      (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of
      CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent
      PCNSL patients. All patients were treated initially with high-dose methotrexate
      (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous
      stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55
      cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10
      patients, respectively. High CD68 expression was associated with inferior overall
      survival (OS) and progression-free survival (PFS) in multivariate analysis (P =
      0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis
      based on upfront ASCT. High CD68 expression was also associated with inferior OS
      and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among
      patients who did not receive upfront ASCT (n = 60), but not in patients who
      received upfront ASCT. The expression of FoxP3 was not significantly associated
      with survival. Therefore, we identified a prognostic significance of high CD68
      expression in PCNSL, which suggests a need for further clinical trials and
      biological studies on the role of PCNSL tumor microenvironment.

PMID- 28508177
TI  - Standing Postural Control in Individuals with Autism Spectrum Disorder:
      Systematic Review and Meta-analysis.
AB  - Impairments in postural control affect the development of motor and social skills
      in individuals with autism spectrum disorder (ASD). This review compared the
      effect of different sensory conditions on static standing postural control
      between ASD and neurotypical individuals. Results from 19 studies indicated a
      large difference in postural control between groups across all sensory
      conditions. This review revealed sensorimotor and multiple sensory processing
      deficits in ASD. The tendency for individuals with ASD to be more susceptible to
      postural instability with use of visual information compared with somatosensory
      information suggests perinatal alterations in sensory development. There is
      further scope for studies on the use of sensory information and postural control
      to provide additional evidence about sensorimotor processing in ASD.

PMID- 28508178
TI  - Survey about the use of clarithromycin in an ENT outpatient department of a
      tertiary hospital.
AB  - We undertook this survey about the use of clarithromycin in the Ear, Nose, and
      Throat (ENT) Outpatient Department of Fudan University Hospital to understand its
      utilization patterns and rational use. A survey of prescriptions given to
      outpatients was carried out, and detailed information of the patients, including
      age, sex, diagnosis, combined medication, and other information, was recorded in
      Excel spreadsheets. The rationale for each prescription was evaluated
      retrospectively. Based on our analysis, 82.5% of the clarithromycin prescriptions
      were for the treatment of rhinosinusitis. It was found that the parameters for
      the diagnosis of this condition were surprisingly broad and should have been more
      specific. In addition, the clarithromycin dosage regimen varied in clinical
      practice. For chronic rhinosinusitis, the duration of treatment was between 8 and
      16 days, which was not sufficient. Moreover, clarithromycin was prescribed along
      with considerable numbers of pharmacotherapeutic anti-allergic drugs. Our survey
      indicated that improvements in the quality of clarithromycin prescriptions in
      otolaryngology outpatients should be made. Furthermore, the importance of medical
      education to patients should be emphasized. In addition, the interaction between
      clarithromycin and other anti-allergic drugs requires further investigation.

PMID- 28508179
TI  - Sternocleidomastoid flap augmentation of the pharyngeal closure after total
      laryngectomy.
AB  - The objective of the study was to evaluate the effect of sternocleidomastoid
      (SCM) flap augmentation of the pharyngeal closure after total laryngectomy on the
      incidence of pharyngocutaneous fistula (PCF). Thirty patients with T4a laryngeal
      carcinoma and none of them receiving primary radiotherapy previously were divided
      into two equal groups. Group A patients had SCM flap augmentation of the
      pharyngeal closure after total laryngectomy. Group B patients had the standard
      pharyngeal closure without augmentation. Both groups were followed up for 30 days
      postoperatively for the development of PCF. The use of the SCM added about extra
      15 min to the surgical procedure in all patients (p < 0.001). The shape of the
      suture line of the neopharynx was horizontal in 14 patients (7 in each group)
      while it was T-shaped in the remaining 16 (8 in each group). Neck dissection was
      done in all patients except only two patients who previously had the neck
      dissection done in combination with partial laryngectomy. Three patients in each
      group developed PCF either early (10 days or less postoperatively) or late (more
      than 10 days but less than 30 days postoperatively). There was no statistically
      significant difference in the length of hospital stay between the two groups. The
      use of SCM flap did not reduce the incidence of PCF after total laryngectomy.

PMID- 28508180
TI  - A study evaluating the effects of throat packs during nasal surgery: a randomised
      controlled trial.
AB  - The aims of this study were to identify differences in post-operative nausea and
      vomiting (PONV) and throat pain between throat packed and non-packed patient
      groups in nasal surgery. This was a prospective, double blind, randomised
      controlled trial. A water-soaked throat pack gauze was inserted in the mouth to
      occlude the oropharynx was used in the throat pack group. The second group
      received no throat pack. A validated PONV questionnaire was completed 6 h post
      operatively. Visual analogue scores (VAS) for throat pain were completed in
      recovery, 2, and 6 h post-operatively. 80 patients were enrolled (40 into each
      group based on power calculation). With regard to the primary outcome measure,
      mean PONV score for the throat pack group was 2.75 [median 0, standard deviation
      (SD 10.86)] and the mean PONV score for the non-packed group was 0.36 (median 0,
      SD 1.39). The difference in PONV was not statistically significant [P value
      0.375, 95% confidence interval (CI) -1.19 to 3.32]. With regard to throat pain
      VAS scores (our secondary outcome measure), in recovery, the mean throat pain VAS
      score for the throat packed group was 2.5 (median 1, SD 2.8) and the mean throat
      pain VAS score for the non-throat packed group was 1.3 (median 0, SD 2.5).
      Statistical analysis showed a significant difference between the two groups with
      the throat pack group experiencing more throat pain in recovery (P value 0.018
      (95% CI 1.13-2.52). At 2 and 6 h post-operatively, the mean throat pain VAS
      scores for the throat packed group were 2.1 and 2.3, respectively, and the mean
      throat pain VAS score for the non-throat packed group was 2.3 and 1.4,
      respectively. Statistical analysis showed non-significant difference between the
      two groups at 2 and 6 h post-operatively. The use of throat packs in nasal
      surgery does not confer PONV reduction benefit. The use of throat pack, however,
      is associated with a small but statistically significant more throat pain in the
      initial recovery period from nasal operations.

PMID- 28508181
TI  - How we do it: the intra-operative identification of a pharyngocele.
AB  - A pharyngocele is an uncommon condition, where pharyngeal mucosa herniates
      through the thyrohyoid membrane. It can be difficult to locate when the patient
      is at rest. To locate the pharyngocele intra-operatively, a bag valve mask was
      used to inflate the herniated mucosa. We describe a cost-effective and simple way
      to locate the pharyngocele intra-operatively.

PMID- 28508182
TI  - New antimicrobial flavonoids and chalcone from Colutea armata.
AB  - Colucins A (1) and B (2), new flavonoids and colucone (3), the new chalcone
      derivative, have been isolated from the CHCl3-soluble fraction of the whole plant
      of Colutea armata along with luteolin (4), luteolin 7-O-beta-D-glucoside (5),
      isoliquiritigenin (6), trans-caffeic acid (7) and stigmasterol (8) reported for
      the first time from this species. Their structures were elucidated by
      spectroscopic techniques including MS and 2D-NMR spectroscopy. Compounds 1 and 2
      showed significant antimicrobial activity against two Gram positive and three
      Gram negative bacterial strains while 3 was moderately active.

PMID- 28508183
TI  - Compositional design and Taguchi optimization of hardness properties in silicone
      based ocular lenses.
AB  - A multi-component acrylate-based copolymer system especially designed for
      application as ocular lenses is developed through free-radical, bulk
      polymerization of a system containing hydroxyethyl methacrylate, methyl
      methacrylate, triethylene glycol dimethacrylate, dimethyl itaconate, 3
      (trimethoxysilyl) propylmethacrylate, Polyhedraloligomeric silsesquioxane
      acrylate (POSS-acrylate) and AIBN as an initiator. The progress of the reaction
      was monitored by Fourier transform infrared spectroscopy (FTIR). The effect of
      increasing concentration of the components on the hardness of the synthesized
      lenses was measured by Shore Durometer before and after immersion in PBS
      solutions. Extraction test method was performed to analyze the biocompatibility
      of the fabricated lenses. In this research the Taguchi method was employed to
      achieve the optimal hardness property which plays a critical role in final
      application of the lens materials. The Taguchi trial for ocular lens hardness was
      configured in an L16 orthogonal array, by five control factors, each with four
      level settings. The results showed that 3-(trimethoxysilyl) propyl methacrylate
      decreases and 2-hydroxyethylmethacrylate increases, polyhedraloligomeric
      silsesquioxane with a cage-like structure, methyl methacrylate and dimethyl
      itaconate increase the hardness. Proliferation and growth of the cells showed
      that there is no toxic substance extracted from the lenses which can interfere
      with the cell growth.

PMID- 28508184
TI  - Nationwide cross-sectional adherence to mammography screening guidelines:
      national behavioral risk factor surveillance system survey results.
AB  - PURPOSE: Varying recommendations about breast cancer screening have generated
      much confusion about when and how often to undergo mammography screening, yet
      there is limited population-based data about the extent to which patients adhere
      to various mammographic screening guidelines in practice. Our purpose was to
      evaluate population-based adherence to mammographic screening using criteria from
      major guideline-producing organizations. METHODS: Women aged 40-74 in the 2014
      Behavioral Risk Factor Surveillance System survey were included. Self-reported
      mammographic screening within 1 or 2 years, according to major guideline
      producing organizations (American Cancer Society [ACS], US Preventative Services
      Task Force [USPSTF], American College of Radiology [ACR], American College of
      Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression,
      adjusting for demographics and indices of access to health care. RESULTS: 159,123
      women were included. By age category, cross-sectional adherence to USPSTF
      guidelines ranged from 76 to 81%, ACS (55-81%) and ACR/ACOG (45-64%) with
      increasing age being associated improved adherence. The highest proportions of
      women undergoing mammographic screening were seen in women ages 65-69 (66% within
      last year, 81% within last 2 years). Statistically significant predictors of
      adherence to mammography screening included increased income category (OR 1.08,
      1.07-1.09), higher education category (OR 1.13, 1.11-1.16), and increased access
      to health care (OR 2.25, 1.94-2.60), adjusted for age categories. CONCLUSIONS:
      Adherence to mammography screening was closest to USPSTF guidelines with 76-81%
      cross-sectional adherence. Frequency of screening increases with age with highest
      screening proportions in women ages 65-69 (66% within last year, 81% within last
      2 years). For all screening guidelines, adherence to mammography screening
      remains poor in women with limited access to health insurance with less than half
      of women obtaining recommended screening.

PMID- 28508186
TI  - Effects of Maternal Zinc Glycine on Mortality, Zinc Concentration, and
      Antioxidant Status in a Developing Embryo and 1-Day-Old Chick.
AB  - This study was conducted to investigate the effects of maternal zinc glycine (Zn
      Gly) supplementation as an alternative for zinc sulfate (ZnSO4) on mortality,
      zinc (Zn) concentration, and antioxidant status in a developing embryo and 1-day
      old chick. Six hundred 39-week-old broiler breeders were randomly assigned to 6
      treatments, each treatment including 5 replicates with 20 birds each. Six
      treatments received a basal diet (control, 24 mg Zn/kg diet) or a basal diet
      supplemented with ZnSO4 (80 mg Zn/kg) or Zn-Gly (20, 40, 60, or 80 mg Zn/kg),
      respectively. The experiment lasted for 8 weeks after a 4-week pre-experiment
      with a basal diet. At the last week, 100 eggs per replicate were randomly
      collected for incubation. Compared with the control treatment, Zn supplementation
      decreased (P < 0.05) embryo mortalities of the late stage and the whole period,
      increased (P < 0.05) liver Zn concentration in the embryo of d9, d19, and 1-day
      old chick, and improved (P < 0.05) antioxidant status in the embryo of d19 and 1
      day-old chick. Compared with the ZnSO4 treatment, 80 mg Zn/kg Zn-Gly treatment
      significantly decreased (P < 0.05) the late stage embryo mortality and increased
      (P < 0.05) liver Zn concentration in the embryo of d9, d19, and 1-day-old chick.
      The 80 mg Zn/kg Zn-Gly treatment significantly increased (P < 0.05) copper-zinc
      superoxide dismutase activity in d19 embryo and 1-day-old chick, total superoxide
      dismutase activity in 1-day-old chick, and copper-zinc superoxide dismutase
      messenger RNA (mRNA) abundance of d9 embryo and 1-day-old chick than that in
      ZnSO4 treatment. The liver metallothionein concentration of the developing embryo
      and 1-day-old chick and its mRNA abundance of d19 embryo were also significantly
      increased (P < 0.05) in the 80 mg Zn/kg Zn-Gly treatment in comparison with ZnSO4
      treatment. In conclusion, maternal Zn supplementation decreased embryo
      mortalities of the late stage and the whole period by increasing liver Zn
      concentration and antioxidant status in d19 embryo and 1-day-old chick, and 80 mg
      Zn/kg from Zn-Gly treatment was the optimum choice.

PMID- 28508187
TI  - Associations Between Serum Zinc Levels and Mental Health: Findings from the 2010
      Korean National Health and Nutrition Examination Survey.
AB  - Mental health problems are a major public health issue worldwide, and zinc may be
      associated with psychiatric symptoms, but such associations have not been
      investigated extensively. This study was conducted to evaluate the relationship
      between serum zinc levels and mental health problems in Korean adults. We used
      data from the Korean National Health and Nutrition Examination Survey V-1, a
      cross-sectional survey of Korean civilians. Data from 1748 subjects were
      analyzed. Serum zinc levels did not differ significantly according to psychiatric
      symptoms including sleep duration, stress, depressed mood, suicidal ideation, and
      whether respondents sought psychiatric consultation. The frequencies and odds
      ratios of psychiatric symptoms according to serum zinc tertiles were not
      significantly associated after adjusting for age, smoking, alcohol consumption,
      physical activity, body mass index, total body fat, and renal function and for
      daily fat, carbohydrate, and protein intake. Serum zinc levels may not be
      associated with psychiatric symptoms in Korean adults without psychiatric
      disorders.

PMID- 28508185
TI  - TITAN: phase III study of doxorubicin/cyclophosphamide followed by ixabepilone or
      paclitaxel in early-stage triple-negative breast cancer.
AB  - PURPOSE: Ixabepilone is a microtubule stabilizer with activity in taxane
      refractory metastatic breast cancer and low susceptibility to taxane-resistance
      mechanisms including multidrug-resistant phenotypes and high beta-III tubulin
      expression. Since these resistance mechanisms are common in triple-negative
      breast cancer (TNBC), ixabepilone may have particular advantages in this patient
      population. This study evaluated the substitution of ixabepilone for paclitaxel
      following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early
      stage TNBC. METHODS: Patients with operable TNBC were eligible following
      definitive breast surgery. Patients were randomized (1:1) to receive four cycles
      of AC followed by either four cycles (12 weeks) of ixabepilone or 12 weekly doses
      of paclitaxel. RESULTS: 614 patients were randomized: 306 to AC/ixabepilone and
      308 to AC/paclitaxel. At a median follow-up of 48 months, 59 patients had
      relapsed (AC/ixabepilone, 29; AC/paclitaxel, 30). The median time from diagnosis
      to relapse was 20.8 months. The 5-year disease-free survival (DFS) rates of the
      two groups were similar [HR 0.92; ixabepilone 87.1% (95% CI 82.6-90.5) vs.
      paclitaxel 84.7% (95% CI 79.7-88.6)]. The estimated 5-year overall survival (OS)
      rates were also similar [HR 1.1; ixabepilone 89.7% (95% CI 85.5-92.7) vs.
      paclitaxel 89.6% (95% CI 85.0-92.9)]. Peripheral neuropathy was the most common
      grade 3/4 event. Dose reductions and treatment discontinuations occurred more
      frequently during paclitaxel treatment. CONCLUSIONS: Treatment with
      AC/ixabepilone provided similar DFS and OS in patients with operable TNBC when
      compared to treatment with AC/paclitaxel. The two regimens had similar toxicity,
      although treatment discontinuation, dose modifications, and overall peripheral
      neuropathy were more frequent with AC/paclitaxel. TRIAL REGISTRATION: Clinical
      Trials.gov Identifier, NCT00789581.

PMID- 28508188
TI  - Trace Element Determination and Cardioprotection of Terminalia pallida Fruit
      Ethanolic Extract in Isoproterenol Induced Myocardial Infarcted Rats by ICP-MS.
AB  - The trace elements and minerals in Terminalia pallida fruit ethanolic extract
      (TpFE) were determined by the instrument inductively coupled plasma-mass
      spectrometry (ICP-MS), and the cardioprotection of TpFE against isoproterenol
      (ISO)-administered rats was studied. Rats were pretreated with TpFE (100, 300,
      and 500 mg/kg bw) for 30 days, with concurrent administration of ISO (85 mg/kg
      bw) for two consecutive days. The levels of trace elements and minerals in TpFE
      were below the permitted limits of World Health Organization standards. ISO
      administration significantly increased the heart weight and cardiac marker
      enzymes in serum, xanthine oxidase, sodium, and calcium in the heart, whereas
      significantly decreased body weight, reduced glutathione, glutathione-S
      transferase, superoxide dismutase, and potassium in the heart. Oral pretreatment
      of TpFE significantly prevented the ISO-induced alterations. This is the first
      report that revealed the determination of trace elements and mineral nutrients of
      TpFE by ICP-MS which plays a principal role in the herbal drug discovery for the
      treatment of cardiovascular diseases.

PMID- 28508189
TI  - The Contribution of Superoxide Radical to Cadmium Toxicity in E. coli.
AB  - Numerous reports suggest the involvement of oxidative stress in cadmium toxicity,
      but the nature of the reactive species and the mechanism of Cd-induced oxidative
      damage are not clear. In this study, E. coli mutants were used to investigate
      mechanisms of Cd toxicity. Effects of Cd on metabolic activity, production of
      superoxide radical by the respiratory chain, and induction of enzymes controlled
      by the soxRS regulon were investigated. In E. coli, the soxRS regulon controls
      defense against O2.-and univalent oxidants. Suppression of metabolic activity,
      inability of E. coli to adapt to new environment, and slow cell division were
      among the manifestations of Cd toxicity. Cd increased production of O2.- by the
      electron transport chain and prevented the induction of soxRS-controlled
      protective enzymes, even when the regulon was induced by the redox-cycling agent,
      paraquat. The effect was not limited to soxRS-dependent proteins and can be
      attributed to previously reported suppression of protein synthesis by Cd.
      Increased production of superoxide, combined with inability to express protective
      enzymes and to replace damaged proteins by de novo protein synthesis, seems to be
      the main reason for growth stasis and cell death in Cd poisoning.

PMID- 28508190
TI  - Assessment of the Zinc and Copper Status in Alpaca.
AB  - This study was performed with the aim of investigating the concentration of zinc
      and copper in the blood of healthy alpacas (Vicugna pacos) kept in central Europe
      and to compare the concentration of Zn and Cu in plasma and in whole blood. A
      further objective was to evaluate blood Zn and Cu in relation to different
      micromineral supplementation, age and sex groups of alpacas. A total of 299
      alpacas (224 adults and 75 crias) from 18 farms were included in this study. The
      concentrations of copper and zinc in plasma/whole blood were measured by flame
      atomic absorption spectrometry. The results of this study show high individual
      variability in plasma Zn (median 3.54, range 1.56-8.01 MUmol/l), whole blood Zn
      (median 10.01, range 6.23-75.0 MUmol/l), plasma Cu (median 7.53, range 2.93-16.41
      MUmol/l) and whole blood Cu (median 6.33, range 3.02-13.95 MUmol/l). Plasma Zn
      was not significantly influenced by sex, age or feeding group. Whole blood Zn was
      only significantly higher in females than in males. The intake of Zn in all
      groups was equal to or higher than the nutritional recommendation. During
      excessive supplementation, Zn absorption decreased and thus blood Zn did not
      reflect the higher intake. Only a weak correlation was found (Spearman
      correlation coefficient r = 0.384; p > 0.01; n = 204) between plasma and whole
      blood Zn concentrations. Plasma copper concentration was significantly influenced
      by age, sex and feeding; whole blood Cu by age and feeding. However, neither
      plasma Cu nor whole blood Cu reflected the intake of the element. We found a
      close correlation between plasma and blood copper concentrations (Spearman
      correlation coefficient r = 0.9043; p <= 0.01; n = 99). According to our results,
      copper in plasma or blood is not a good indicator of copper intake.

PMID- 28508191
TI  - Investigations of severity level measurements for diabetic macular oedema using
      machine learning algorithms.
AB  - BACKGROUND: The macula is an important part of the human visual system and is
      responsible for clear and colour vision. Macular oedema happens when fluid and
      protein deposit on or below the macula of the eye and cause the macula to thicken
      and swell. Normally, it occurs due to diabetes called diabetic macular oedema.
      Diabetic macular oedema (DME) is one of the main causes of visual impairment in
      patients. AIM: The aims of the present study are to detect and localize
      abnormalities in blood vessels with respect to macula in order to prevent vision
      loss for the diabetic patients. METHODS: In this work, a novel fully computerized
      algorithm is used for the recognition of various diseases in macula using both
      fundus images and optical coherence tomography (OCT) images. Abnormal blood
      vessels are segmented using thresholding algorithm. The classification is
      performed by three different classifiers, namely, the support vector machine
      (SVM), cascade neural network (CNN) and partial least square (PLS) classifiers,
      which are employed to identify whether the image is normal or abnormal.
      CONCLUSION: The results of all of the classifiers are compared based on their
      accuracy. The classifier accuracies of the SVM, cascade neural network and
      partial least square are 98.33, 97.16 and 94.34%, respectively. While analysing
      DME using both images, OCT produced efficient output than fundus images.
      Information about the severity of the disease and the localization of the
      pathologies is very useful to the ophthalmologist for diagnosing disease and
      choosing the proper treatment for a patient to prevent vision loss.

PMID- 28508192
TI  - Ultrasound-guided fine needle aspiration versus core needle biopsy: comparison of
      post-biopsy hematoma rates and risk factors.
AB  - PURPOSE: To compare post-biopsy hematoma rates between ultrasound guided-fine
      needle aspiration and ultrasound guided-core needle biopsy, and to investigate
      risk factors for post-biopsy hematoma. METHODS: A total of 5304 thyroid nodules
      which underwent ultrasound guided biopsy were included in this retrospective
      study. We compared clinical and US features between patients with and without
      post-biopsy hematoma. Associations between these features and post-biopsy
      hematoma were analyzed. RESULTS: Post-biopsy hematoma rate was 0.8% (43/5121) for
      ultrasound guided-fine needle aspiration and 4.9% (9/183) for ultrasound guided
      core needle biopsy (P < 0.001). For ultrasound guided-fine needle aspiration,
      gender, age, size, presence of vascularity, and suspicious US features were not
      associated with post-biopsy hematoma according to experience level. Post-biopsy
      hematoma occurred significantly more with ultrasound guided-core needle biopsy
      (9/179, 5.0%) than with ultrasound guided-fine needle aspiration (9/1138, 0.8%)
      (P < 0.001) in experienced performers and ultrasound guided-core needle biopsy
      was the only significant risk factor for post-biopsy hematoma (adjusted Odds
      Ratio, 6.458, P < 0.001). CONCLUSION: Post-biopsy hematoma occurred significantly
      more in ultrasound guided-core needle biopsy than in ultrasound guided-fine
      needle aspiration and ultrasound guided-core needle biopsy was the only
      independent factor of post-biopsy hematoma in thyroid nodules.

PMID- 28508193
TI  - Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in
      mice.
AB  - PURPOSE: Non-alcoholic fatty liver disease is highly associated with morbidity
      and mortality in population. Although studies have already demonstrated that the
      immune response plays a pivotal role in the development of non-alcoholic fatty
      liver disease, the comprehensive regulation is unclear. Therefore, present study
      was carried out to investigate the non-alcoholic fatty liver disease development
      under neutrophil depletion. METHODS: To achieve the aim of the study, C57BL/6 J
      mice were fed with high fat diet for 6 weeks before treated with neutrophil
      deplete antibody 1A8 or isotype control (200 MUg/ mouse every week) for another 4
      weeks. RESULTS: Treated with 1A8 antibody, obese mice exhibited better whole body
      metabolic parameters, including reduction of body weight gain and fasting blood
      glucose levels. Neutrophil depletion also effectively reduced hepatic structural
      disorders, dysfunction and lipid accumulation. Lipid beta-oxidative markers,
      phosphorylated-AMP-activated protein kinase alpha and phosphorylated-acetyl-CoA
      carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The
      mitochondrial number and function were also reversed after 1A8 antibody
      treatment, including increased mitochondrial number, reduced lipid oxidative
      damage and enhanced mitochondrial activity. Furthermore, the expression of
      inflammatory cytokines, tumor necrosis factor-alpha, interleukin-6, and monocyte
      chemoattractant protein-1 were obviously reduced after neutrophil depletion,
      accompanied with decreased F4/80 mRNA level and macrophage percentage in liver.
      The decreased NF-kappaB signaling activity was also involved in the beneficial
      effect of neutrophil depletion. CONCLUSION: Taken together, neutrophil depletion
      could attenuate metabolic syndromes and hepatic dysfunction.

PMID- 28508194
TI  - Fatty liver as a risk factor for progression from metabolically healthy to
      metabolically abnormal in non-overweight individuals.
AB  - PURPOSE: Recent studies identified that metabolically abnormal non-obese
      phenotype is a risk factor for cardiovascular diseases. However, little is known
      about risk factor for progression from metabolically healthy non-overweight to
      metabolically abnormal phenotype. We hypothesized that fatty liver had a clinical
      impact on progression from metabolically healthy non-overweight to metabolically
      abnormal phenotype. METHODS: In this retrospective cohort study, 14,093 Japanese
      (7557 men and 6736 women), who received the health-checkup program from 2004 to
      2012, were enrolled. Overweight and obesity were defined as body mass index 23.0
      25.0 and >=25.0 kg/m2. Four metabolic factors (impaired fasting glucose,
      hypertension, hypertriglyceridemia and low high density lipoprotein-cholesterol
      concentration) were used for definition of metabolically healthy (less than two
      factors) or metabolically abnormal (two or more). We divided the participants
      into three groups: metabolically healthy non-overweight (9755 individuals,
      men/women = 4290/5465), metabolically healthy overweight (2547 individuals,
      1800/747) and metabolically healthy obesity (1791 individuals, 1267/524). Fatty
      liver was diagnosed by ultrasonography. RESULTS: Over the median follow-up period
      of 5.3 years, 873 metabolically healthy non-overweight, 512 metabolically healthy
      overweight and 536 metabolically healthy obesity individuals progressed to
      metabolically abnormal. The adjusted hazard risks of fatty liver on progression
      were 1.49 (95% confidence interval 1.20-1.83, p = 0.005) in metabolically healthy
      non-overweight, 1.37 (1.12-1.66, p = 0.002) in metabolically healthy overweight
      and 1.38 (1.15-1.66, p < 0.001) in metabolically healthy obesity, after adjusting
      for age, sex, alcohol, smoking, exercise, impaired fasting glucose, hypertension,
      hypertriglyceridemia, low high density lipoprotein-cholesterol concentration, and
      abdominal obesity. CONCLUSIONS: Fatty liver is an independent risk factor for
      progression from metabolically healthy status to metabolically abnormal
      phenotype, even in non-overweight individuals.

PMID- 28508196
TI  - Genetic relationship and biological status of the industrially important yeast
      Saccharomyces eubayanus Sampaio et al.
AB  - The genomes of the recently discovered yeast Saccharomyces eubayanus and
      traditional S. cerevisiae are known to be found in the yeast S. pastorianus (syn.
      S. carlsbergensis), which are essential for brewing. The cryotolerant yeast S.
      bayanus var. uvarum is of great importance for production of some wines. Based on
      ascospore viability and meiotic recombination of the control parental markers in
      hybrids, we have shown that there is no complete interspecies post-zygotic
      isolation between the yeasts S. eubayanus, S. bayanus var. bayanus and S. bayanus
      var. uvarum. The genetic data presented indicate that all of the three taxa
      belong to the same species.

PMID- 28508195
TI  - Serum p53 antibody as a potential tumor marker in extrahepatic
      cholangiocarcinoma.
AB  - PURPOSE: Only a few studies have evaluated the clinicopathological significance
      of the p53 protein expression and s-p53-Abs level in patients with
      cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic
      significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma.
      METHODS: We prospectively evaluated s-p53-Abs levels before and after surgery in
      61 patients with extrahepatic cholangiocarcinoma to determine the relationship
      between clinicopathological factors and the prognostic significance of s-p53-Abs.
      RESULTS: Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23%
      were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum
      markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)
      significantly increased the rate of positive extrahepatic cholangiocarcinoma
      cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs,
      P = 0.035). There were no significant differences in clinicopathological factors
      between the p53-seropositive and p53-seronegative patients. An
      immunohistochemical analysis showed the presence of significant associations
      between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity
      and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic
      factor for the survival in either univariate or multivariate analyses, p53
      immunoreactivity was independently associated with a poor survival. Among
      patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced
      after surgery in most. CONCLUSION: These findings suggested that s-p53-Abs might
      be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for
      a diagnosis, but was not useful for predicting tumor recurrence or the survival.
      This study was registered as UMIN000014530.

PMID- 28508197
TI  - Antinociceptive effect of the agonist of 5-HT1A receptors buspirone in the model
      of abdominal pain in dogs.
AB  - We have demonstrated that activation of 5-HT1A receptors with buspirone promotes
      visceral analgesia in awake dogs. The administration of 0.035 mg/kg (i.m.) of the
      drug caused depression of viscero-motor (contraction of the abdominal muscles)
      and pressor (increase in the heart rate) responses to noxious distension of the
      large intestine. An increase in the dose to 0.07 and 0.14 mg/kg did not enhance
      the antinociceptive effect of buspirone but triggered basal tachycardia. The
      obtained results provide evidence of the inhibitory role of 5-HT1A receptors in
      modulating visceral pain sensitivity and the possibility of an exciting effect of
      their activation on the cardiovascular system.

PMID- 28508198
TI  - Role of the low-selective organic anion transport in regulation of osmotic
      balance of renal collecting duct principal cells under hypo-osmotic conditions.
AB  - In the course of adaptation of the rat kidney collecting duct cells to hypo
      osmotic medium, the organic anion transporter inhibitor probenecid reduced
      significantly the regulatory cell volume decrease in response to a hypotonic
      shock. Both probenecid and hypotonic shock delayed significantly the entry into a
      cell of the fluorescent dye calcein, which exists as anion at neutral pH. Thus,
      the organic osmolyte transport plays an important role in the regulatory decrease
      of the principal cell volume under the hypo-osmotic conditions.

PMID- 28508199
TI  - Selective specificity of calcium-binding proteins calbindin and calretinin
      expression in the magnocellular neurosecretory hypothalamic nuclei of tortoises
      and turtles.
AB  - We have studied the distribution of calcium-binding proteins in the magnocellular
      neurosecretory nuclei of nonapeptidergic neurosecretory nuclei of the preoptic
      hypothalamic complex in a tortoise (Testudo horsfieldi) and a pond turtle (Emys
      orbicularis) using immunohistochemistry. We have found that different types of
      cells in the paraventricular and supraoptic nuclei predominantly express
      calbindin and, to a lesser extent, calretinin, but not parvalbumin. The selective
      calbindin/calretinin control of the neurohormone secretion in these hypothalamic
      nuclei is an evolutionary conservative feature typical of reptiles and mammals.

PMID- 28508200
TI  - Individual variability of human olfactory sensitivity to volatile steroids:
      Environmental and genetic factors.
AB  - The sensitivity to androstenone and possible factors, determining the sensitivity
      were investigated for the large sample of inhabitants of central Russia (n =
      860). Specific anosmia was detected in 48.8% of subjects. Women were more
      sensitive to androstenone than men. The proportion of men, but not women
      perceiving the smell of androstenone as a strong one in the concentration used
      decreased with age. Smoking, blood group, or ethnicity had no significant effect
      on the expression of specific anosmia and the perception of androstenone odor
      intensity.

PMID- 28508201
TI  - Heterochronies in the cranial development of Asian tree frogs (Amphibia: Anura:
      Rhacophoridae) with different life histories.
AB  - The development of bony skull was studied in four species of Asian tree frogs
      (Rhacophoridae) with different life histories: biphasic development with free
      larval stage and direct development. In biphasic rhacophorids the sequence of the
      appearance of cranial bones generally followed the generalized pattern of
      craniogenesis, which was described for most studied anurans. In contrast, direct
      developing species displayed some heterochronies in the formation of skull bones,
      namely, the accelerated formation of the anlagen of jaw and suspensorium bones.
      The obtained results support that the embryonization in amphibians is regularly
      accompanied by a heterochronic repatterning of craniogenesis, rather similar in
      different phyletic groups.

PMID- 28508202
TI  - Ozone concentration in the ground atmosphere and morbidity during extreme heat in
      the summer of 2010.
AB  - Dependence of the population morbidity on the ground-level ozone concentration in
      the summer of 2010 was studied in a city with low urbanization (Vyatskie Polyany,
      Kirov oblast) and in Moscow. At a high air temperature and low ozone
      concentration, the population morbidity was not associated with these parameters
      in Vyatskie Polyany. When the average daily ground-level ozone concentration
      exceeded 60 MUg/m3 for 13 successive days, the correlation coefficient between
      ozone concentration and the number of ambulance calls was statistically
      significant, r = 0.62. Heavy smoke from forest fires reduced ozone concentration,
      and the number of emergency calls did not increase. In Moscow, the incidence of
      respiratory diseases and population mortality were growing up at high ozone
      concentrations.

PMID- 28508203
TI  - Plasma corticosterone concentrations in European robins during spring and autumn
      migration.
AB  - To estimate differences in hormonal mechanisms of regulation of spring and autumn
      migration in European robins Erithacus rubecula, the plasma corticosterone (CORT)
      concentrations were compared in birds caught during both migratory seasons. A
      total of 414 blood samples were analyzed. It was found that the baseline and
      stress-induced CORT concentrations in free-living robins during spring migration
      were practically twice as high as during autumn passage. Our results demonstrate
      that autumn and spring migrations are independent stages of the avian annual
      cycle. Probably, the increase in the CORT concentrations in spring can be
      considered to be physiological preparation for the breeding season.

PMID- 28508204
TI  - Rearing by foster Wistar mother with high level of maternal care counteracts the
      development of genetic absence epilepsy and comorbid depression in WAG/Rij rats.
AB  - It has been shown for the first time that rearing by a foster Wistar mother with
      high level of maternal care (MC) counteracts the expression of genetic absence
      epilepsy (AE) and comorbid depression - reduces the number, duration and index of
      spike-wave discharges (SWDs) and immobility time in the forced swimming test, as
      well as exerts substantial effects on morphology and time-frequency dynamics of
      SWDs in WAG/Rij rats. It is supposed that increases in MC early in development
      might be used to counteract epileptogenesis and comorbid depression in people
      genetically predisposed to AE.

PMID- 28508205
TI  - The first case of morphological differentiation of Altai Osman Oreoleuciscus
      potanini (Cyprinidae, Actinopterigii) in a river.
AB  - The variability of osteological characters has been investigated in cyprinid fish
      of the genus Oreoleuciscus (Potanin Altai osman) from the river Zavkhan; this
      fish species is endemic for water bodies of Central Asia. Multivariate analysis
      of 13 quantitative parameters of the size of the cerebral and visceral skull and
      the pectoral girdle and the construction of ontogenetic channels allowed the
      detection of morphologically distinct forms in the fluvial habitats. The result
      obtained provides additional proof of the possibility of sympatric
      diversification of fish in river ecosystems. One of the two fluvial forms
      discovered has been shown to be identical (with regard to the osteological
      characters) to a previously described herbivorous form of O. potanini from the
      standing water bodies of the Great Lakes Hollow (Western Mongolia).

PMID- 28508206
TI  - Rapid use of resources as a basis of the Heracleum sosnowskyi invasive syndrome.
AB  - The functional properties of the invasive Heracleum sosnowskyi were compared with
      those of the native Heracleum sibiricum. The leaf and root traits, as well as
      those of a whole plant and of the mycorrhiza formation, were studied. H.
      sosnowskyi can fulfill the high-productivity potential only under the optimum
      availability of resources (especially water), while it is poorly adapted to
      maintain a high physiological activity under the unfavorable soil conditions. An
      important component of the H. sosnowskyi invasiveness is an ability to utilize
      rapidly resources in both the above- and underground areas at the optimum
      conditions.

PMID- 28508207
TI  - New aspects of the Seam4D-dependent control of lymphocyte activation.
AB  - Novel targets for action of the class IV semaphorin Seam4D have been identified
      in the immune system. The low-affinity CD72 receptor for Seam4D was detected not
      only on B lymphocytes, but also in a proportion of T cells, whereas the high
      affinity semaphorin receptor, plexin B1, originally considered to belong to non
      immune cells, proved to be in a great proportion of intact T and B cells. Seam4D
      is constitutively expressed in B cells, which, along with T cells, can serve as a
      source of both membrane and soluble semaphorin. The results obtained make
      significant adjustments in understanding of Seam4D effects in lymphoid cells.

PMID- 28508208
TI  - The meio- to macrozoobenthos ratio in a lake benthic community: Dynamic aspect.
AB  - Multiyear data (2002-2015) on the biomasses of meio- and macrozoobenthic
      communities have been studied at different depths of a small lake in northern
      Karelia. A trend towards anti-phase changes in meio- and macrobenthic biomasses
      was observed and, as a consequence, the ratio between these components varied
      significantly in different years. Thus, inter-annual dynamics should be taken
      into account in analysis of hydrobiological data.

PMID- 28508209
TI  - Estimates of underwater and aerial visual acuity in the European beaver Castor
      fiber L. based on morphological data.
AB  - The eye optics and topographic distribution of ganglion cells were studied using
      whole mount preparations from European beaver Castor fiber L. The beaver eye
      optics provides emmetropia in air and hypermetropia in water. The optometrical
      measurements predict retinal resolution of the beaver eye around 17' in air and
      9' in water. In air, retinal resolution corresponds to the real visual acuity,
      whereas in water, visual acuity is below the retinal resolution because of the
      non-precise focusing.

PMID- 28508210
TI  - Reverse Genetics for Mammalian Orthoreovirus.
AB  - Reverse genetics allows introduction of specific alterations into a viral genome.
      Studies performed with mutant viruses generated using reverse genetics approaches
      have contributed immeasurably to our understanding of viral replication and
      pathogenesis, and also have led to development of novel vaccines and virus-based
      vectors. Here, we describe the reverse genetics system that allows for production
      and recovery of mammalian orthoreovirus, a double-stranded (ds) RNA virus, from
      plasmids that encode the viral genome.

PMID- 28508211
TI  - Development and Characterization of an Infectious cDNA Clone of Equine Arteritis
      Virus.
AB  - Development and characterization of several infectious cDNA clones of equine
      arteritis virus (EAV) have been described in the literature. Here we describe the
      assembly of the full-length infectious cDNA clone of the virulent Bucyrus strain
      (VBS; ATCC VR-796) of EAV in a plasmid vector. This system allows generation of
      infectious in vitro-transcribed (IVT) RNA from the linearized plasmid that can be
      transfected or electroporated into mammalian cells to produce infectious
      recombinant progeny virus. This is an efficient reverse genetics system that
      allows easy manipulation of EAV genomes to study molecular biology of the virus
      and pathogenesis of equine viral arteritis.

PMID- 28508212
TI  - Reverse Genetics for Porcine Reproductive and Respiratory Syndrome Virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is a reemerging swine
      disease, and has become economically the most significant disease in pork
      production worldwide. The causative agent is PRRS virus (PRRSV), which is a
      member virus of the family Arteriviridae. The PRRSV genome is a single-stranded
      positive-sense RNA and is infectious. Two strategies in the PRRSV reverse
      genetics system have been employed for reconstitution of progeny virus: RNA
      transfection and DNA transfection. The PRRSV reverse genetics has broadly been
      used for studies including protein structure-function relationship, foreign gene
      expression, vaccine development, virulence determinants, and viral pathogenesis.
      Herein, we describe the modification of the pFL12 "RNA launch" reverse genetic
      system to the CMV promoter-driven pXJ41-FL13 "DNA launch" system. The generation
      of progeny PRRSV using pXJ41-FL13 is further elucidated.

PMID- 28508213
TI  - Reverse Genetics of Zika Virus.
AB  - We have established a reverse genetic system for Zika virus (ZIKV). Five shuttle
      plasmids were constructed and assembled into the full-length cDNA clone of ZIKV
      genome. To ensure the stability of the cDNA clone, we used a low copy vector
      (pACYC177) and a set of unique restriction enzyme sites on the ZIKV genome to
      assemble the full-length cDNA clone. A T7 promoter was engineered in front of the
      viral 5' UTR for in vitro transcription. A hepatitis delta virus ribozyme (HDVr)
      sequence was engineered following the viral 3' UTR for generation of the
      authentic 3' end of the RNA transcript.

PMID- 28508214
TI  - Efficient Reverse Genetic Systems for Rapid Genetic Manipulation of Emergent and
      Preemergent Infectious Coronaviruses.
AB  - Emergent and preemergent coronaviruses (CoVs) pose a global threat that requires
      immediate intervention. Rapid intervention necessitates the capacity to generate,
      grow, and genetically manipulate infectious CoVs in order to rapidly evaluate
      pathogenic mechanisms, host and tissue permissibility, and candidate antiviral
      therapeutic efficacy. CoVs encode the largest viral RNA genomes at about 28
      32,000 nucleotides in length, and thereby complicate efficient engineering of the
      genome. Deconstructing the genome into manageable fragments affords the
      plasticity necessary to rapidly introduce targeted genetic changes in parallel
      and assort mutated fragments while maximizing genome stability over time. In this
      protocol we describe a well-developed reverse genetic platform strategy for CoVs
      that is comprised of partitioning the viral genome into 5-7 independent DNA
      fragments (depending on the CoV genome), each subcloned into a plasmid for
      increased stability and ease of genetic manipulation and amplification.
      Coronavirus genomes are conveniently partitioned by introducing type IIS or IIG
      restriction enzyme recognition sites that confer directional cloning. Since each
      restriction site leaves a unique overhang between adjoining fragments,
      reconstruction of the full-length genome can be achieved through a standard DNA
      ligation comprised of equal molar ratios of each fragment. Using this method,
      recombinant CoVs can be rapidly generated and used to investigate host range,
      gene function, pathogenesis, and candidate therapeutics for emerging and
      preemergent CoVs both in vitro and in vivo.

PMID- 28508216
TI  - Rescue of Sendai Virus from Cloned cDNA.
AB  - Sendai virus (SeV) is a non-segment negative-sense RNA virus that naturally
      infects and causes pneumonia in mice. As a prototypic member of the family
      Paramyxoviridae, SeV has been characterized well, and these studies revealed
      numerous traits of paramyxovirus biology. The reverse genetics system to rescue
      SeV was first established in 1995. The virus was rescued from a cloned cDNA that
      contains full genome sequence flanked by T7 promoter and hepatitis delta virus
      ribozyme. To rescue SeV, it is necessary to infect cells with a recombinant
      vaccinia virus vTF7.3 that expresses T7 RNA polymerase, and transfect with the
      SeV full genome cDNAs together with supporting plasmids encoding NP, P, and L
      genes under the T7 promoter. Synthesized viral RNA by T7 RNA polymerase will be
      encapsidated with NP and associated with a polymerase complex composed of P and
      L. The polymerase complex transcribes and replicates the genome, and produces
      progeny virions. Rescued SeV needs to be plaque purified to exclude vTF7.3 from
      viral stock. Reverse genetics system of SeV is relatively efficient compared to
      other paramyxoviruses, but alternative approaches to rescue poorly growing mutant
      viruses are also available.

PMID- 28508215
TI  - Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus.
AB  - We have developed a reverse genetics system for the avian coronavirus infectious
      bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV
      genome is inserted into the vaccinia virus genome under the control of a T7
      promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has
      the advantage that modifications can be introduced into the IBV cDNA using
      homologous recombination, a method frequently used to insert and delete sequences
      from the vaccinia virus genome. Here, we describe the use of transient dominant
      selection as a method for introducing modifications into the IBV cDNA that has
      been successfully used for the substitution of specific nucleotides, deletion of
      genomic regions, and exchange of complete genes. Infectious recombinant IBVs are
      generated in situ following the transfection of vaccinia virus DNA, containing
      the modified IBV cDNA, into cells infected with a recombinant fowlpox virus
      expressing T7 DNA-dependant RNA polymerase.

PMID- 28508217
TI  - BAC-Based Recovery of Recombinant Respiratory Syncytial Virus (RSV).
AB  - Respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand
      RNA virus, which causes lower respiratory tract infections and is a leading cause
      of mortality in young infants. There is no available RSV vaccine and currently
      administered prophylactic antibodies are limited to high-risk populations.
      Current efforts to develop vaccines include development of live-attenuated RSV
      candidates. We describe here methods for preparation and recovery of recombinant
      RSV using an efficient bacterial artificial chromosome (BAC)-based system,
      expansion and plaque purification of recovered virus, and generation of master
      and working stocks.

PMID- 28508218
TI  - Recovery of a Paramyxovirus, the Human Metapneumovirus, from Cloned cDNA.
AB  - Human metapneumovirus (HMPV), a single-stranded negative-sense RNA virus
      belonging to the family Paramyxoviridae, is associated with respiratory tract
      illness, primarily in young children and persons with underlying disease. Based
      on genetic and antigenic variation, HMPV strains are classified into two
      serotypes, with isolates NL/1/00 and NL/1/99 as prototypes for serotypes A and B,
      respectively. The development of plasmid-based reverse genetics systems for both
      serotypes has resulted in developments of a wide range of vaccine candidates
      against HMPV infection. The approach to virus rescue of HMPV is similar to that
      used for other paramyxoviruses, starting with mini-replicon assays for
      optimizations of the rescue protocols and subsequent replacement of the mini
      genome with a plasmid expressing the cDNA of the full-length viral RNA genome.
      Here, we provide detailed information on the reverse genetics systems for HMPV.

PMID- 28508219
TI  - Reverse Genetics of Newcastle Disease Virus.
AB  - Reverse genetics allows for the generation of recombinant viruses or vectors used
      in functional studies, vaccine development, and gene therapy. This technique
      enables genetic manipulation and cloning of viral genomes, gene mutation through
      site-directed mutagenesis, along with gene insertion or deletion, among other
      studies. An in vitro infection-based system including the highly attenuated
      vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage
      T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid,
      was successfully developed to rescue genetically modified Newcastle disease
      viruses in 1999. In this chapter, the materials and the methods involved in
      rescuing Newcastle disease virus (NDV) from cDNA, utilizing site-directed
      mutagenesis and gene replacement techniques, are described in detail.

PMID- 28508220
TI  - Reverse Genetics Systems for Filoviruses.
AB  - Filoviruses are among the most pathogenic viruses known to man. Reverse genetics
      systems, in particular full-length clone systems, allow the generation of
      recombinant filoviruses, which can be used to study virus biology, but also for
      applied uses such as screening for countermeasures. Here we describe the
      generation of recombinant filoviruses from cDNA.

PMID- 28508222
TI  - Lassa Virus Reverse Genetics.
AB  - The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several
      hundred thousand people yearly in West Africa, resulting in high numbers of Lassa
      fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity
      and mortality. To date, no licensed vaccines are available to LASV infections,
      and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that
      is only partially effective. The development of reverse genetics has provided
      investigators with a novel and powerful approach for the investigation of the
      molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV
      minigenome (MG) systems has allowed examining the cis- and trans-acting factors
      involved in genome replication and gene transcription and the identification of
      novel drugable LASV targets. Likewise, it is now feasible to rescue infectious
      recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations
      in their genomes to investigate virus-host interactions and mechanisms of
      pathogenesis, as well as to facilitate screens to identify antiviral drugs
      against LASV and the implementation of novel strategies to develop live
      attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art
      experimental procedures for implementation of LASV reverse genetics. In addition,
      we will briefly discuss some significant translational research developments that
      have been made possible upon the development of LASV reverse genetics.

PMID- 28508221
TI  - Rapid Reverse Genetics Systems for Rhabdoviruses: From Forward to Reverse and
      Back Again.
AB  - Methods to recover recombinant negative strand RNA viruses (rNSVs) from cloned
      cDNAs have been significantly improved in more than two decades of NSV reverse
      genetics . In particular, for non-segmented negative strand RNA viruses (NNSVs )
      like rhabdoviruses , time-consuming generation of reverse genetics systems by
      stitching PCR subfragments of genomic rhabdovirus cDNAs using ligase-based
      conventional cloning approaches limited the number of available recombinant virus
      cDNA clones. As genetic variability is considered an intrinsic feature of RNA
      viruses, it is thus reasonable to conclude that reverse genetics approaches to
      investigate natural virus functions and pathogenesis require improved systems
      that reflect the complexity of naturally occurring wild-type viruses, and that
      largely exclude adaption to cell culture conditions.In order to allow rapid
      cloning of wild-type NSV genome populations into reverse genetics vector
      plasmids, we developed a system in which cDNA copies of complete rhabdovirus
      populations are inserted into a plasmid bank by linear-to-linear homologous
      RecE/T recombination (LLHR ). Limited requirements for sequence information a
      priori, high cloning efficiencies, and the possibility to directly generate
      recombinant viruses from individual cDNA clones now offer novel opportunities to
      combine forward genetic dissection of natural rhabdovirus populations and
      downstream reverse genetics approaches.

PMID- 28508223
TI  - Reverse Genetics of Influenza B Viruses.
AB  - Annual influenza epidemics are caused not only by influenza A viruses but also by
      influenza B viruses. Initially established for the generation of recombinant
      influenza A viruses, plasmid-based reverse genetics techniques have allowed
      researchers the generation of wild type and mutant viruses from full-length cDNA
      copies of the influenza viral genome. These reverse genetics approaches have
      allowed researchers to answer important questions on the biology of influenza
      viruses by genetically engineering infectious recombinant viruses. This has
      resulted in a better understanding of the molecular biology of influenza viruses,
      including both viral and host factors required for genome replication and
      transcription. With the ability to generate recombinant viruses containing
      specific mutations in the viral genome, these reverse genetics tools have also
      allowed the identification of viral and host factors involved in influenza
      pathogenesis, transmissibility, host-range interactions and restrictions, and
      virulence. Likewise, reverse genetics techniques have been used for the
      implementation of inactivated or live-attenuated influenza vaccines and the
      identification of anti-influenza drugs and their mechanism of antiviral activity.
      In 2002, these reverse genetics approaches allowed also the recovery of
      recombinant influenza B viruses entirely from plasmid DNA. In this chapter we
      describe the cloning of influenza B/Brisbane/60/2008 viral RNAs into the
      ambisense pDP-2002 plasmid and the experimental procedures for the successful
      generation of recombinant influenza B viruses.

PMID- 28508224
TI  - Rescue of Infectious Salmon Anemia Virus (ISAV) from Cloned cDNA.
AB  - The piscine Orthomyxovirus called Infectious Salmon Anemia Virus (ISAV) is one of
      the most important emerging pathogens affecting the salmon industry worldwide.
      The first reverse genetics system for ISAV, which allows the generation of
      recombinant ISA virus (rISAV), is an important tool for the characterization and
      study of this fish virus. The plasmid-based reverse genetics system for ISAV
      includes the use of a novel fish promoter, the Atlantic salmon internal
      transcribed spacer region 1 (ITS-1). The salmon, viral and mammalian genetic
      elements included in pSS-URG vectors allow the expression of the eight viral RNA
      segments. In addition to four cytomegalovirus (CMV)-based vectors that express
      the four proteins of the ISAV ribonucleoprotein complex, the eight pSS-URG
      vectors allowed the generation of infectious rISAV in salmon cells.

PMID- 28508226
TI  - Erratum to: Introducing precise genetic modifications into human 3PN embryos by
      CRISPR/Cas-mediated genome editing.

PMID- 28508225
TI  - Plasmid-Based Reverse Genetics of Influenza A Virus.
AB  - Influenza A viruses have broad host range with a recognized natural reservoir in
      wild aquatic birds. From this reservoir, novel strains occasionally emerge with
      the potential to establish stable lineages in other avian and mammalian species,
      including humans. Understanding the molecular changes that allow influenza A
      viruses to change host range is essential to better assess their animal and
      public health risks. Reverse genetics systems have transformed the ability to
      manipulate and study negative strand RNA viruses. In the particular case of
      influenza A viruses, plasmid-based reverse genetics approaches have allowed for a
      better understanding of, among others, virulence, transmission, mechanisms of
      antiviral resistance, and the development of alternative vaccines and vaccination
      strategies. In this chapter we describe the cloning of cDNA copies of viral RNA
      segments derived from a type A influenza virus into reverse genetics plasmid
      vectors and the experimental procedures for the successful generation of
      recombinant influenza A viruses.

PMID- 28508227
TI  - The MDM2 promoter T309G polymorphism was associated with preeclampsia
      susceptibility.
AB  - PURPOSE: Preeclampsia (PE) is a hypertensive disorder of pregnancy in which
      abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role
      in its pathophysiology. The aim of the current study was to examine the
      association between Mouse Double Minute 2 (MDM2) T309G and 40 bp
      insertion/deletion (I/D) polymorphisms and PE risk. METHODS: A case-control study
      was conducted on 208 PE women and 164 healthy pregnant women matching age, sex,
      and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and PCR methods were used for genotyping. RESULTS: The MDM2 309GG
      genotype was associated with PE, and this genotype was found to be a risk factor
      for PE. There was no association between the MDM2 I/D polymorphism and PE. The
      haplotype-based association analysis revealed no association between MDM2 T309G
      and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined
      genotypes were significantly higher in PE women with marginal P values (P =
      0.046). CONCLUSIONS: The MDM2 309GG genotype was associated with higher risk of
      PE. The TT-DD and GG-DD combined genotypes were higher in PE women.

PMID- 28508229
TI  - Return to sports after ACL reconstruction: a paradigm shift from time to
      function.

PMID- 28508228
TI  - Relationship between white blood cell count elevation and clinical response after
      G-CSF priming chemotherapy for acute myeloid leukemia.
AB  - We retrospectively analyzed the relationship between white blood cell (WBC) count
      elevation after priming and clinical response in 115 patients with AML (61
      untreated and 54 relapsed or refractory) treated with low-dose cytarabine,
      aclarubicin, and G-CSF priming. Receiver operating characteristic curve analysis
      showed that the ratio of maximum WBC count to pretreatment WBC count (WBCratio)
      was most strongly associated with complete remission (CR) in previously untreated
      patients among several parameters we analyzed in this study; however, the
      prediction accuracy was not clinically significant considering the area under the
      curve of 0.694. Based on the cutoff value of the WBCratio, CR rate and event-free
      survival in the high WBCratio group were significantly better than those in the
      low WBCratio group in untreated patients. Regarding the WBC differential counts,
      a high ratio of the maximum to pretreatment value of neutrophils rather than that
      of peripheral blasts was associated with a superior CR rate. In addition, an
      increase in blasts after G-CSF priming had a significant negative impact on CR
      rate in untreated patients. In conclusion, an increase in blast counts after G
      CSF priming was not predictive of achieving CR.

PMID- 28508230
TI  - Erratum to: Exposure to di-2-ethylhexyl terephthalate in a convenience sample of
      U.S. adults from 2000 to 2016.

PMID- 28508231
TI  - Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti
      cancer drug target.
AB  - The aryl hydrocarbon receptor (AhR) was initially identified as the receptor that
      binds and mediates the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and structurally related halogenated aromatics. Other toxic
      compounds including some polynuclear aromatic hydrocarbons act through the AhR;
      however, during the last 25 years, it has become apparent that the AhR plays an
      essential role in maintaining cellular homeostasis. Moreover, the scope of
      ligands that bind the AhR includes endogenous compounds such as multiple
      tryptophan metabolites, other endogenous biochemicals, pharmaceuticals and health
      promoting phytochemicals including flavonoids, indole-3-carbinol and its
      metabolites. It has also been shown that like other receptors, the AhR is a drug
      target for multiple diseases including cancer, where both AhR agonists and
      antagonists effectively block many of the critical hallmarks of cancer in
      multiple tumor types. This review describes the anti-cancer activities of AhR
      ligands and demonstrates that it is time to separate the AhR from TCDD and
      exploit the potential of the AhR as a novel target for cancer chemotherapy.

PMID- 28508232
TI  - Is Routine Prophylactic Cholecystectomy Necessary During Gastrectomy for Gastric
      Cancer? Reply.

PMID- 28508233
TI  - Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon
      Cancer Shows Comparable Results and Identifies Patients with Decreased Survival:
      A Prospective Single-Center Trial.
AB  - BACKGROUND: Sentinel lymph node (SLN) mapping was reported to improve lymph node
      staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine
      green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor
      cells (ITC) and micro-metastases in upstaged patients. METHODS: A total of 220
      stage I-III colon cancer patients were included in this prospective single-center
      study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50
      patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If
      negative for tumor infiltration, immunostaining for cytokeratin (AE1/3;
      cytokeratin-19) was performed. RESULTS: SLN detection rate for IB and ICG was 100
      and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64%
      for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node
      negative. In these patients, ITC and micro-metastases were detected in 26%
      (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro
      metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09)
      compared to node negative disease. CONCLUSIONS: This study demonstrates a high
      diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged
      a quarter of patients with node negative colon cancer, and the detected ITC and
      micro-metastases were an independent negative prognostic marker in multivariate
      analysis.

PMID- 28508234
TI  - Surgical Treatment of Extraesophageal Manifestations of Gastroesophageal Reflux
      Disease.
AB  - OBJECTIVE: To review the current literature on the role of antireflux surgery
      (ARS) for the treatment of extraesophageal manifestations of GERD. The
      extraesophageal manifestations of gastroesophageal reflux disease (GERD) include
      chronic cough, laryngopharyngeal reflux, and asthma. They are responsible for
      significant morbidity in affected patients and a high economic burden on
      healthcare resources. We recently published a larger review on the symptoms,
      diagnosis, medical, and surgical treatment of the extraesophageal manifestations
      of GERD. Through our investigation, we found that the role of ARS for respiratory
      symptoms was unclear. Hence, we resorted through the data of our previous meta
      analysis to compile a comprehensive and focused review on the role of ARS for
      respiratory symptoms. METHODS: Using the archive of our previous meta-analysis,
      we selected studies extracted from the MEDLINE, Cochran, PubMed, Google Scholar,
      and Embase databases pertaining to the surgical treatment of extraesophageal
      manifestations of reflux (cough laryngopharyngeal reflux, and asthma). We applied
      a similar reporting methodology as was used in our previous manuscript and then
      hand searched the bibliographies of included studies yielding a total of 27
      articles for review. We graded the level of evidence and classified
      recommendations by size of treatment effect per the American Heart Association
      Task Force on Practice Guidelines. RESULTS: Observational data indicated that
      syndromes of chronic cough, laryngopharyngeal reflux and asthma might improve
      after antireflux surgery only in highly selected patients-likely those with non
      acid reflux-while those patients with objective markers of asthma severity do
      not. Because of the varied methods of diagnosis and surgical technique, non
      comparative observational data may be unreliable. Additionally, our search found
      no randomized controlled trials (RCTs) comparing antireflux surgery to medical
      therapy in the treatment of cough or laryngopharyngeal reflux. One RCT compared
      medical treatment to antireflux surgery in patients with asthma, but medical
      treatment included high-dose H2 blockers instead of PPIs. CONCLUSIONS:
      Extraesophageal manifestations of GERD are common, costly, and difficult to
      treat. ARS might be effective in highly selected patients, especially in those
      whose extraesophageal manifestations are caused by non-acid reflux. The available
      data to date are generally of poor quality or outdated. Well-designed randomized
      controlled trials or large-scale observational cohort studies are urgently
      needed.

PMID- 28508235
TI  - The Presence of Postoperative Infectious Complications is Associated with the
      Risk of Early Postoperative Clinical Recurrence of Crohn's Disease.
AB  - BACKGROUND: The purpose of the study was to identify risk factors for early
      clinical and surgical recurrence in Crohn's disease (CD) patients who underwent
      intestinal resection. METHOD: This was a retrospective study. Consecutive
      patients who underwent intestinal resection with a primary anastomosis from
      January 2011-December 2014 were enrolled. Gender, age at surgery, clinical
      phenotypes of CD, serum albumin and C-reactive protein level the day before
      surgery, smoking status at surgery, anastomosis technique, number of anastomoses,
      details of postoperative complications, the postoperative prophylactic treatment
      were assessed to figure out risk factors for postoperative clinical and surgical
      recurrence within 1 year after the initial resection by univariate and then
      multivariate analysis. RESULTS: Two hundred and thirty-seven patients were
      analyzed. The risk of early postoperative clinical recurrence was 2.99 times
      higher in patients suffered postoperative infectious complications [odds ratio
      (OR) 2.99; 95% CIs, 1.42-6.32; p = 0.004], while never-smoking was found to be a
      protective factor for early clinical recurrence (OR 0.326; 95% CIs, 0.18-0.59; p
      < 0.0001). For surgical recurrence within 1 year after resection, the presence of
      postoperative intra-abdominal septic complications might be a risk factor (OR
      6.77; 95% CIs, 1.61-28.5; p = 0.009). Smoker at surgery was also a risk factor
      for early surgical recurrence (OR 5.41; 95% CIs, 1.36-21.5; p = 0.017).
      CONCLUSION: The presence of postoperative infectious complications was identified
      as a possible risk factor for early postoperative clinical recurrence after
      resection in CD patients.

PMID- 28508236
TI  - An Exploratory Analysis of the Geographical Distribution of Trauma Incidents in
      Shenzhen, China.
AB  - BACKGROUND: The city of Shenzhen, China, is planning to establish a trauma
      system. At present, there are few data on the geographical distribution of
      incidents, which is key to deciding on the location of trauma centres. The aim of
      this study was to perform a geographical analysis in order to inform the
      development of a trauma system in Shenzhen. METHODS: Retrospective analysis of
      trauma incidents attended by Shenzhen Emergency Medical Services (EMS) in 2014.
      Data were obtained from Shenzhen EMS. Incident distribution was explored using
      dot and kernel density estimate maps. Clustering was determined using the nearest
      neighbour index. The type of healthcare facilities which patients were taken to
      was compared against patients' needs, as assessed using the Field Triage Decision
      Scheme. RESULTS: There were 49,082 recorded incidents. A total of 3513 were
      classed as major trauma. Mapping demonstrates that incidents predominantly
      occurred in the western part of Shenzhen, with identifiable clusters. Nearest
      neighbour index was 0.048. Of patients deemed to have suffered major trauma, 8.5%
      were taken to a teaching hospital, 13.6% to a regional hospital, 42.6% to a
      community hospital, and 35.3% to a private hospital. The proportions of Step 1 or
      2 negative patients were almost identical. CONCLUSION: The majority of trauma
      patients, including trauma patients who are at greater likelihood of severe
      injury, are taken to regional and community hospitals. There are areas with
      identifiable concentrations of volume, which should be considered for the siting
      of high-level trauma centres, although further modelling is required to make firm
      recommendations.

PMID- 28508239
TI  - Double crush syndrome caused by cervical spondylosis and vertebral artery loop.
AB  - PURPOSE: The purpose of this article is to report a successful treatment
      experience in a rare case of simultaneous cervical nerve root compression by
      spondylotic cervical foraminal stenosis and a vertebral artery loop. METHODS: 51
      year-old man presented with a 4-year history of left-sided cervical pain
      radiating to the left shoulder with progressive exacerbation of weakness on left
      shoulder girdle muscles for 7 months. The patient had no history of trauma. The
      patient's CT and MRI revealed impingement of the left C6 cervical nerve root by a
      tortuous vertebral artery loop and also by narrowed left C5-6 cervical foramen
      that had undergone spondylotic changes. The patient underwent left C5-6
      hemilaminectomy, facetectomy and C5-6 fusion. The procedures were uneventful, and
      the patient recovered with complete resolution of symptoms. RESULTS: The patient
      continued to be asymptomatic at a 2-year follow-up examination, and the muscle
      mass of his left girdle returned normal. CONCLUSIONS: This report illustrates the
      first phenomenon of a double crush syndrome caused by vertebral artery loop and
      cervical spondylotic changes. When patients with cervical spondylosis present
      with unexplainably severe pain and weakness, additional underlying pathologies
      should be considered when making differential diagnoses. The investigation
      planning should involve electromyography, computed tomography angiography, and
      magnetic resonance imaging.

PMID- 28508238
TI  - Surgical excision for recurrent herpes simplex virus 2 (HSV-2) anogenital
      infection in a patient with human immunodeficiency virus (HIV).
AB  - Recurrent anogenital herpes simplex virus infections are common in patients with
      human immunodeficiency virus (HIV), of whom approximately 5% develop resistance
      to acyclovir. We present a case of a 49-year-old man with HIV who had an 8-year
      history of recurrent left inguinal herpes simplex virus type 2 ulcerations. He
      initially responded to oral acyclovir, but developed resistance to acyclovir and
      eventually foscarnet. The lesion progressed to a large hypertrophic mass that
      required surgical excision, which led to resolution without recurrences. Our case
      highlights the importance of surgical excision as a treatment option in
      refractory herpes simplex virus anogenital infections.

PMID- 28508240
TI  - Atlantoaxial dislocation and os odontoideum in two identical twins: perspectives
      on etiology.
AB  - PURPOSE: There are two theories about the origin of os odontoideum: traumatic or
      congenital. However, most studies favor the hypothesis of traumatic theory. To
      emphasize the congenital theory, we report a pair of identical twins both with
      atlantoaxial dislocation and os odontoideum, which is believed to be a congenital
      defect. METHODS: We present two 14-year-old identical twins with atlantoaxial
      dislocation and os odontoideum. Neither of the twins had history of trauma in
      head nor cervical spine. We reviewed and compared the cervical radiographs of the
      identical twins. Posterior atlantoaxial reduction, pedicle screw fixation and
      atlantoaxial fusion were performed for the two twins. RESULTS: Radiological
      examination showed the identical twins had typical atlantoaxial dislocation and
      os odontoideum. The twins had high similarity in the appearance of atlantoaxial
      dislocation and os odontoideum. The etiology of the os odontoideum in the twins
      is believed to be congenital. Both the twins had improvement in neurological
      function after surgery. CONCLUSION: Although a great number of cases with os
      odontoideum have been reported to be traumatic, there are some cases believed to
      be congenital.

PMID- 28508241
TI  - Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for
      Neovascular Age-Related Macular Degeneration in the UK: Interim Results from
      TERRA.
AB  - INTRODUCTION: Ranibizumab is an inhibitor of vascular endothelial growth factor-A
      (anti-VEGF) approved for the treatment of neovascular age-related macular
      degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce
      the burden of clinic visits compared with a pro re nata (PRN) regimen.
      Retrospective, interim analyses of clinical effectiveness, treatment and resource
      use patterns were conducted using real-world data in England and Wales from the
      TERRA study. METHODS: Two cohorts, those switching from a PRN to a T&E regimen
      ('prior PRN') and those initiating ranibizumab on the T&E regimen as their first
      anti-VEGF therapy ('anti-VEGF-naive') were enrolled in TERRA. Retrospective
      clinical assessments were gathered from medical records, while resource use
      patterns were collected via an operating cost questionnaire completed by each
      study site. RESULTS: At the interim analysis cut-off date (15 November 2016), 11
      sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naive: n = 35).
      Mean change from baseline (date of first injection) in visual acuity and central
      subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic
      Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n =
      27] and -67.7 MUm (95% CI -106.5, -28.9; p = 0.001, n = 29), respectively, in the
      anti-VEGF-naive cohort. Most T&E clinics were run as one-stop services (same-day
      monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services
      (monitoring and injection on different days). In general, one-stop clinics used
      less staff resources and were likely to be shorter in duration for healthcare
      providers than the cumulative time spent for two-stop clinics. CONCLUSION: This
      is the first real-world observational study conducted in England and Wales
      demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naive
      patients. T&E is compatible with one-stop clinic services, which these real-world
      data suggest to be less resource intensive than two-stop clinic services,
      possibly providing a dosing regimen beneficial to both patients and resource
      burden in UK clinical practice. FUNDING: Novartis Pharmaceuticals UK Limited.

PMID- 28508237
TI  - Development of a Unifying Target and Consensus Indicators for Global Surgical
      Systems Strengthening: Proposed by the Global Alliance for Surgery, Obstetric,
      Trauma, and Anaesthesia Care (The G4 Alliance).
AB  - After decades on the margins of primary health care, surgical and anaesthesia
      care is gaining increasing priority within the global development arena. The 2015
      publications of the Disease Control Priorities third edition on Essential Surgery
      and the Lancet Commission on Global Surgery created a compelling evidenced-based
      argument for the fundamental role of surgery and anaesthesia within cost
      effective health systems strengthening global strategy. The launch of the Global
      Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has
      further coordinated efforts to build priority for surgical care and anaesthesia.
      These combined efforts culminated in the approval of a World Health Assembly
      resolution recognizing the role of surgical care and anaesthesia as part of
      universal health coverage. Momentum gained from these milestones highlights the
      need to identify consensus goals, targets and indicators to guide policy
      implementation and track progress at the national level. Through an open
      consultative process that incorporated input from stakeholders from around the
      globe, a global target calling for safe surgical and anaesthesia care for 80% of
      the world by 2030 was proposed. In order to achieve this target, we also propose
      15 consensus indicators that build on existing surgical systems metrics and
      expand the ability to prioritize surgical systems strengthening around the world.

PMID- 28508242
TI  - Preclinical study of a cost-effective photodynamic therapy protocol for treating
      oral candidoses.
AB  - Photodynamic therapy (PDT) is a promising treatment for oral candidoses. Its use
      as an alternative to antifungals prevents several adverse effects, including
      microbial resistance. However, most PDT protocols do not employ devices and
      consumables commonly available in dental practice, thus influencing treatment
      affordability. This study aimed to determine the efficacy of a PDT method based
      on light curing units' blue LEDs combined to a plaque-disclosing composition (5%
      erythrosine) against C. albicans in culture and in a murine model of oral
      candidosis. Standard and resistant fungal strains were tested in vitro in
      planktonic and biofilm forms. PDT (pre-irradiation time periods: 30 and 60 s;
      irradiation time: 3 min) was compared to control conditions without light and/or
      erythrosine. Mice with induced oral candidosis (n = 40) randomly received PDT or
      similar control conditions with subsequent C. albicans count. These mice
      underwent histological analysis, as well as 12 healthy mice submitted to
      experimental treatments. PDT completely inactivated C. albicans planktonic cells
      and biofilm. Control conditions presented minor differences (ANOVA, p < 0.05),
      with mean values ranging from 5.2 to 6.8 log10 (UFC/mL). Infected mice presented
      no significant difference in C. albicans counts consequent to treatments (ANOVA,
      p = 0.721), although the PDT protocol was able to enhance the inflammatory
      infiltrate in healthy mice. It can be concluded that the tested PDT protocol can
      inactivate C. albicans but still needs further investigation in order to achieve
      efficacy and safety.

PMID- 28508243
TI  - Low-level laser treatment stimulates hair growth via upregulating Wnt10b and beta
      catenin expression in C3H/HeJ mice.
AB  - This study was conducted in order to evaluate the role of low-level laser
      treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were
      randomly divided into two groups: with and without low-level laser treatment. The
      skin color of each mouse was observed each day. Skin samples were collected for
      H&E, immunofluorescence, PCR, and western blot analysis, to observe the
      morphology of hair follicles and detect the expression levels of Wnt10b and beta
      catenin. Observation of skin color demonstrated that black pigmentation started
      significantly earlier in the laser group than in the control group. Hair follicle
      number in both groups showed no difference; however, the hair follicle length
      presented a significant difference. Wnt10b protein was detected on the second day
      in hair matrix cells in the LLLT group but not in the control group. PCR and
      western blot results both illustrated that expression of Wnt10b and beta-catenin
      was significantly higher in the LLLT group than in the control group. Our study
      illustrated that low-level laser treatment can promote hair regrowth by inducing
      anagen phase of hair follicles via initiating the Wnt10b/beta-catenin pathway.

PMID- 28508245
TI  - Evaluation of macular and peripapillary choroidal thickness, macular volume and
      retinal nerve fiber layer in acromegaly patients.
AB  - PURPOSE: To evaluate macular volume, retinal nerve fiber layer, and macular and
      peripapillary choroidal thickness in acromegaly patients. METHOD: In this
      prospective, case-control study, 31 patients with acromegaly and 32 healthy
      subjects were recruited. Only right eyes were evaluated. Macular choroidal
      thickness (CT) was measured at three points, peripapillary CT was measured at
      eight points, and macular volume was measured at nine areas in the central 6 mm
      circle zone by spectraldomain optical coherence tomography (OCT). Retinal nerve
      fiber layer (RNFL) was measured automatically at six segments by OCT. RESULTS:
      The mean macular and peripapillary CT at all measuring points were significantly
      higher in acromegaly group (p < 0.05). RNFL thicknesses were significantly higher
      in acromegaly except for temporal segment (p < 0.05). The mean total, inferior
      and superior retinal volume of the macula were significantly higher in acromegaly
      group (p < 0.001), whereas there was no statistically difference was seen in
      retinal volume of temporal and nasal macular area between the two groups (p >
      0.05). CONCLUSION: The macular and peripapillary choroidal thickness, retinal
      nerve fiber layer, and total retinal volume of the macula were significantly
      higher in acromegaly patients. Increased choroidal thickness may cause different
      macular pathologies such as choroidal neovascularization. RNFL results may be
      important in acromegaly patients with glaucoma, especially if the progress of
      glaucoma is monitored by OCT.

PMID- 28508244
TI  - Interventions for the endodontic management of non-vital traumatised immature
      permanent anterior teeth in children and adolescents: a systematic review of the
      evidence and guidelines of the European Academy of Paediatric Dentistry.
AB  - AIM: This systematic review was undertaken in order to develop guidelines for the
      European Academy of Paediatric Dentistry for the management of non-vital
      permanent anterior teeth with incomplete root development. METHODS: Three
      techniques were considered; apexification by single or multiple applications of
      calcium hydroxide, use of Mineral Trioxide Aggregate (MTA) for the creation of an
      apical plug followed by obturation of the root canal, and finally a Regenerative
      Endodontic Technique (RET). Scottish Intercollegiate Guideline Network (SIGN)
      Guidelines (2008) were used for the synthesis of evidence and grade of
      recommendation. RESULTS: Variable levels of evidence were found and generally
      evidence related to these areas was found to be weak and of low quality. It was
      not possible to produce evidence-based guidelines based on the strength of
      evidence that is currently available for the management of non-vital immature
      permanent incisors. CONCLUSIONS: Based on the available evidence the European
      Academy of Paediatric Dentistry proposes Good Clinical Practice Points as a
      guideline for the management of such teeth. It is proposed that the long term use
      of calcium hydroxide in the root canals of immature teeth should be avoided and
      apexification with calcium hydroxide is no longer advocated. The evidence related
      to the use of a Regenerative Endodontic Technique is currently extremely weak and
      therefore this technique should only be used in very limited situations where the
      prognosis with other techniques is deemed to be extremely poor. The current
      review supports the use of MTA followed by root canal obturation as the treatment
      of choice.

PMID- 28508246
TI  - The significance of histological analysis following laser transurethral resection
      of the prostate.
AB  - PURPOSE: Monopolar transurethral resection of the prostate is the gold standard
      for the treatment of benign prostatic hyperplasia. However, due to the associated
      risks of bleeding and TUR syndrome, laser prostate surgery is gaining popularity.
      We perform thulium-laser vaporesection of the prostate (TmLRP), where
      histological samples are generated in every case. We determined postoperative
      incidence and significance of prostate cancer detection, by retrospective
      histological examination of our cases. METHODOLOGY: Between October 2006 and
      August 2012, 223 patients underwent TmLRP by a single surgeon in our institution.
      With a background of a benign DRE, and no suspicion of CaP, histological results
      were studied. RESULTS: Mean age was 71 years (range 46-91), mean PSA was 4.1
      ng/mL (range 0.1-20). 4.9% (11/223) had cancer prostate (CaP) diagnosed, with
      mean PSA of 6.9 ng/mL (range 0.7-14). Of these: 91% (10/11) had pT1b disease
      while 9% (1/11) had pT1a disease. Gleason score was 6 in 28% (3/11); 7 in 36%
      (4/11); 8 in 18% (2/11); 9 in and 18% (2/11). CONCLUSION: 4.9% of patients had
      unexpected CaP, with significant disease in 4.4% (pT1b) and 3.6% (Gleason score
      >=7). Hence, patients should be advised of the small risk of missing significant
      unsuspected CaP after laser prostatectomy.

PMID- 28508248
TI  - Endogenous versus exogenous generic reference pricing for pharmaceuticals.
AB  - In this paper we carry out a vertical differentiation duopoly model applied to
      pharmaceutical markets to analyze how endogenous and exogenous generic reference
      pricing influence competition between generic and branded drugs producers. Unlike
      the literature, we characterize for the exogenous case the equilibrium prices for
      all feasible relevant reference prices. Competition is enhanced after the
      introduction of a reference pricing system. We also compare both reference
      pricing systems on welfare grounds, assuming two different objective functions
      for health authorities: (i) standard social welfare and (ii) gross consumer
      surplus net of total pharmaceutical expenditures. We show that regardless of the
      objective function, health authorities will never choose endogenous reference
      pricing. When health authorities are paternalistic, the exogenous reference price
      that maximizes standard social welfare is such that the price of the generic drug
      is the reference price while the price of the branded drug is higher than the
      reference price. When health authorities are not paternalistic, the optimal
      exogenous reference price is such that the price of the branded drug is the
      reference price while the price of the generic drug is lower than the reference
      price.

PMID- 28508247
TI  - In human cell cultures, everolimus is inferior to tacrolimus in inhibiting
      cellular alloimmunity, but equally effective as regards humoral alloimmunity.
AB  - PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft
      failure early in the course of kidney transplantation, whereas chronic antibody
      mediated rejection is a major contributor to graft loss in the late post
      transplant phase. Based mainly on the results of short-term studies, the
      calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin
      (mTOR) inhibitors. However, the toxicity profile of the two drug categories
      differs, making the interchange between them appealing. In this study, the effect
      of tacrolimus and of the mTOR inhibitor everolimus on cellular and humoral
      alloimmunity was evaluated. METHODS: Cellular alloimmunity was assessed by cell
      proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral
      blood mononuclear cells (PBMC). For assessing humoral alloimmunity, we developed
      a method in which humoral alloimmunity was induced in a one-way MLR. The de novo
      production of alloantibodies was measured with an antibody-mediated complement
      dependent cytotoxicity assay, in which supernatants from the above MLRs were used
      against resting PBMC similar to the stimulator cells of the forementioned MLRs.
      Tacrolimus and everolimus were used at concentrations near their upper
      recommended trough levels. RESULTS: In two-way MLRs, tacrolimus inhibited cell
      proliferation more than everolimus. In one-way MLRs, tacrolimus and everolimus
      decreased alloantibody production to the same extent. CONCLUSIONS: In human cell
      cultures, everolimus is inferior to tacrolimus in inhibiting cellular
      alloimmunity, but equally effective as regards humoral alloimmunity. Thus,
      everolimus might be a safe alternative in case of tacrolimus toxicity,
      particularly after the early period of kidney transplantation.

PMID- 28508249
TI  - Self- and Peer-Identified Victims in Late Childhood: Differences in Perceptions
      of the School Ecology.
AB  - Patterns of adjustment for youth victimized by peers vary depending on whether
      youth are identified as victims through self-reports, peer-reports, or both. In
      order to provide more targeted strategies that may help mitigate negative
      consequences associated with specific victimization groups, more information is
      needed about how these youth perceive their school ecology (bullying and academic
      ecology), their feelings of school belonging, and their valuing of school. Based
      on the convergence of self- and peer-reports of victimization, we identified four
      victim groups from a sample of students in 5th grade classrooms (N = 1360; 52.8%
      girls, 53.1% White, 34.6% Black or Hispanic, 12.2% Native American, Asian, or
      other) using Latent Profile Analysis (LPA): convergent victims (high self- and
      peer-reports), self-identified victims (high self-, low peer-reports), peer
      identified victims (low self-, high peer-reports), and nonvictims (low self- and
      peer-reports). Convergent victims' perceptions were similar to nonvictims with
      key differences being convergent victims' greater willingness to protect peers
      being bullied but lower feelings of school belonging compared to nonvictims. Peer
      identified and self-identified victims perceived differences in the bullying and
      academic ecology including peer-identified victims' greater willingness to
      protect peers and expectations for more peers to encourage bulling against them
      compared to self-identified victims. However, both peer- and self-identified
      victims perceived greater emotional risk of participating in class and had lower
      feelings of school belonging compared to nonvictims. Implications for supporting
      youth with divergent self- and peer-reported victimization status as they
      transition to middle school are discussed.

PMID- 28508250
TI  - A Real-world Analysis of Treatment Patterns for Cholinesterase Inhibitors and
      Memantine among Newly-diagnosed Alzheimer's Disease Patients.
AB  - INTRODUCTION: Alzheimer's disease (AD) is the most common neurodegenerative form
      of dementia. Pharmacological therapies for symptomatic treatment, such as
      acetylcholinesterase inhibitors (AChEIs) and memantine, have been available in
      the USA since 2000. Over the past decade, few studies have analyzed real-world
      anti-dementia treatment patterns in the USA. This study evaluated monotherapy
      AChEIs and memantine treatment patterns among newly diagnosed AD patients.
      METHODS: A retrospective cohort study was conducted using Medicare data and the
      Minimum Data Set from 2008 to 2012. Patients aged 65-100 years with newly
      diagnosed AD (ICD-9 code: 331.0) and monotherapy AChEI or memantine treatment
      initiated after diagnosis were included. Descriptive treatment pattern analyses,
      including discontinuation and switch, were undertaken. Kaplan-Meier curves were
      developed to examine the treatment duration. RESULTS: A total of 9812 newly
      diagnosed AD patients were identified, with 56.7% (n = 5567) first receiving anti
      dementia treatment after the initial AD diagnosis. Among patients initiating
      monotherapy AChEIs or memantine after AD diagnosis (N = 5200), 51.6% continued
      index treatment during the entire follow-up period (mean follow-up: 659.7 days)
      and 21.7% discontinued treatment. Of those who initiated monotherapy treatment
      with an AChEI, 11.1% received adjunct therapy with memantine. Among patients with
      >=1 year of continuous treatment (mean follow-up: 834 days), 75.6% remained on
      the index drug, 10.2% discontinued during the remaining follow-up period, and
      9.5% of the AD patients initiating AChEIs received adjunct memantine therapy
      during the remaining follow-up period. CONCLUSION: In the USA Medicare
      population, about 50% of the patients who initiated treatment with AChEI or
      memantine after diagnosis continued the index treatment, and more than 20%
      discontinued and were untreated afterwards over the observation period. AD
      patients initiating AChEIs or memantine were more likely to remain on their
      treatment if they were persistently treated for the first year.

PMID- 28508251
TI  - Occlusion of a Long-Term Transpleural Biliary Drainage Tract Using a Gelatin
      Pledget (Hep-PlugTM).
AB  - This case describes a technique used to close a long-term 14F transpleural
      biliary drainage catheter tract to prevent biliopleural fistula and further
      complications. We deployed a compressed gelatin foam pledget provided in a pre
      loaded delivery device (Hep-PlugTM) along the intrahepatic tissue tract for
      sealing it against the pleural cavity. The device used is easy to handle and
      gives the Interventional Radiologist the possibility to safely manage and prevent
      complications after percutaneous transhepatic interventions.

PMID- 28508252
TI  - Anatomical Variants in Prostate Artery Embolization: A Pictorial Essay.
AB  - Prostate artery embolization (PAE) has emerged as a new treatment option for
      patients with symptomatic benign prostatic hyperplasia. The main challenges
      related to this procedure are navigating arteries with atherosclerosis and
      anatomical variations, and the potential risk of non-target embolization to
      pelvic structures due to the presence of collateral shunts and reflux of
      microparticles. Knowledge of classical vascular anatomy and the most common
      variations is essential for safe embolization, good clinical practice, and
      optimal outcomes. The aim of this pictorial essay is to illustrate the pelvic
      vascular anatomy relevant to PAE in order to provide a practical guide that
      includes the most common anatomical variants as well as to discuss the technical
      details related to each.

PMID- 28508253
TI  - Image-Guided Transarterial Chemoembolization With Drug-Eluting Beads Loaded with
      Doxorubicin (DEBDOX) for Unresectable Hepatic Metastases from Melanoma: Technique
      and Outcomes.
AB  - PURPOSE: Hepatic metastasis from melanoma represents a therapeutic dilemma, with
      limited effective options for the 85% of cases deemed unresectable. Systemic
      agents confer toxicity and, along with traditional local hepatic arterial
      directed therapies such as transarterial chemoembolization, have not led to a
      significant increase in survival. The aim of this study was to investigate the
      safety and dose-limiting toxicity of DEBDOX for the treatment of unresectable
      hepatic metastases from melanoma. METHODS: A multicenter (University of
      Louisville, Thomas Jefferson University, MD Anderson Cancer Center), prospective,
      non-controlled treatment trial (NCT01010984) of hepatic-directed therapy with
      DEBDOX for the treatment of melanoma liver metastasis was reviewed. Primary
      endpoints were response rates by modified response evaluation criteria in solid
      tumors, hepatic progression-free survival (PFS), and overall survival (OS).
      RESULTS: Twenty patients received a total of 61 DEBDOX treatments from January
      2010 to March 2013. The median hepatic tumor burden was 40% (range 20-55), 18
      patients (90%) had bilobar disease, and 13 patients (65%) had concomitant
      extrahepatic disease. At median assessment of 2.5 months, 11 patients (55%)
      exhibited a tumor response and 16 (80%) exhibited disease control. Median follow
      up was 5 months (range 1.1-34.3 months). Median hepatic PFS was 3 months (95% CI
      1.4, 3.4), and OS was 5 months (95% CI 3.3, 10.5). CONCLUSIONS: Directed arterial
      therapy with DEBDOX is effective in managing unresectable liver-dominant
      metastasis from melanoma and should be considered a therapeutic option in the
      multidisciplinary treatment of this disease. Concurrent systemic therapy is
      merited given the high rate of extrahepatic progression. CLINICAL TRIAL:
      NCT01010984.

PMID- 28508254
TI  - Comparison of Pain Within 24 h after Uterine Artery Embolization with Tris-Acryl
      Gelatin Microspheres Versus Gelatin Sponge Particles for Leiomyoma.
AB  - PURPOSE: To compare acute pain after uterine artery embolization (UAE) with tris
      acryl gelatin microspheres (TAGM) versus gelatin sponge particles (GS) for
      leiomyoma. MATERIALS AND METHODS: This was a single-institution, retrospective
      study. Between July 2008 and November 2016, 101 consecutive patients with
      symptomatic uterine leiomyoma underwent UAE with the same protocol for post
      procedural pain. GS was employed with near-stasis endpoint for the first 49
      patients, whereas TAGM was used with limited endpoint for the next 52 patients.
      Post-UAE pain levels were compared between both groups with a linear mixed model
      using visual analog scale (VAS) scores from 0 to 18 h as a repeat measure
      outcome. Peak VAS < 24 h or dose of drugs for analgesia and conscious sedation
      was compared by analysis of variance. Tumor infarction was assessed with post
      procedural contrast-enhanced MRI. RESULTS: Baseline demographics and most
      outcomes including tumor infarction were similar between both groups. The average
      VAS scores during the period <24 h were significantly lower in TAGM group (1.68,
      95% CI 1.23-2.13) compared to GS group (3.28, 95% CI 2.82-3.74, p < 0.0001). The
      difference remained significant even after adjustment for other factors (p <
      0.0001). The mean peak VAS < 24 h was also lower in TAGM group (3.89, 95% CI 3.25
      4.53) than in GS group (5.90, 95% CI 5.20-6.53, p < 0.0001). The dose of drugs
      for analgesia and conscious sedation was significantly lower in TAGM group (p =
      0.001, p = 0.004, respectively). CONCLUSION: TAGM had an advantage over GS in UAE
      for leiomyoma in terms of less post-procedural pain <24 h, with lower doses of
      drugs for analgesia and conscious sedation.

PMID- 28508255
TI  - Psychosocial Patient-Reported Outcomes in Pediatric and Adolescent Diabetes: a
      Review and Case Example.
AB  - PURPOSE OF REVIEW: The purpose of this review is to define psychosocial patient
      reported outcomes (PROs) relevant to pediatric and adolescent diabetes
      populations. Potential domains for PROs include a spectrum of emotional,
      behavioral, social, physical, overall health, and/or care management areas. A
      literature review of potential PRO measures, selection criteria, and
      implementation strategies including a case example will be presented. RECENT
      FINDINGS: Among the pediatric, adolescent, and emerging adult populations,
      research indicates a relative higher risk for distress, depression, anxiety, and
      eating disorders as compared to peers without diabetes. Use of PRO measures can
      expand providers' focus beyond glycemic control, or simply hemoglobin A1c, to
      better appreciate the impact of diabetes on the whole child/adolescent, and
      provide services that address patients' individually identified needs, which are
      most salient to them. Successful selection and implementation of psychosocial PRO
      measures should be designed to include pathways for real-time provider
      interaction with the patient and respective PRO data to guide clinical care.

PMID- 28508257
TI  - Diagnosing Allergic Contact Dermatitis Through Elimination, Perception, Detection
      and Deduction.
AB  - Several authors have commented upon the skills of detection required in making a
      diagnosis of allergic contact dermatitis. Here, we emphasise the search for clues
      in a systematic manner. We describe four stages as part of a systematic method
      for diagnosing allergic contact dermatitis. Firstly, elimination (or inclusion)
      of non-allergic diagnoses. Secondly, perception: the pre-patch test diagnosis and
      the 'three scenarios' principle. Thirdly, detection: optimising the sensitivity
      of the patch test process. Fourthly, deduction: diagnosing allergic contact
      dermatitis by associating the dermatitis with the allergen exposure. We further
      compare and contrast the pre-patch test history and examination with the markedly
      different one ('microhistory' and 'microexamination') used after patch testing.
      The importance of knowledge of contact dermatitis literature is emphasised with a
      review of recent publications. Finally, we also highlight the use of contact
      allergy profiling as an investigative tool in the diagnosis of allergic contact
      dermatitis.

PMID- 28508256
TI  - The Role of Micronutrients in Alopecia Areata: A Review.
AB  - Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune
      mediated attack of the hair follicle. As with other immune-mediated diseases, a
      complex interplay between environment and genetics is thought to lead to the
      development of AA. Deficiency of micronutrients such as vitamins and minerals may
      represent a modifiable risk factor associated with development of AA. Given the
      role of these micronutrients in normal hair follicle development and in immune
      cell function, a growing number of investigations have sought to determine
      whether serum levels of these nutrients might differ in AA patients, and whether
      supplementation of these nutrients might represent a therapeutic option for AA.
      While current treatment often relies on invasive steroid injections or
      immunomodulating agents with potentially harmful side effects, therapy by
      micronutrient supplementation, whether as a primary modality or as adjunctive
      treatment, could offer a promising low-risk alternative. However, our review
      highlights a need for further research in this area, given that the current body
      of literature largely consists of small case-control studies and case reports,
      which preclude any definite conclusions for a role of micronutrients in AA. In
      this comprehensive review of the current literature, we found that serum vitamin
      D, zinc, and folate levels tend to be lower in patients with AA as compared to
      controls. Evidence is conflicting or insufficient to suggest differences in
      levels of iron, vitamin B12, copper, magnesium, or selenium. A small number of
      studies suggest that vitamin A levels may modify the disease. Though
      understanding of the role for micronutrients in AA is growing, definitive
      clinical recommendations such as routine serum level testing or therapeutic
      supplementation call for additional studies in larger populations and with a
      prospective design.

PMID- 28508258
TI  - Spatiotemporal analysis the precipitation extremes affecting rice yield in
      Jiangsu province, southeast China.
AB  - With the increasing risk of meteorological disasters, it is of great importance
      to analyze the spatiotemporal changes of precipitation extremes and its possible
      impact on rice productivity, especially in Jiangsu province, southeast China. In
      this study, we explored the relationships between rice yield and extreme
      precipitation indices using Mann-Kendall trend test, Pettitt's test, and K-means
      clustering methods. This study used 10 extreme precipitation indices of the rice
      growing season (May to October) based on the daily precipitation records and rice
      yield data at 52 meteorological stations during 1961-2012 in Jiangsu province.
      The main findings were as follows: (1) correlation results indicated that
      precipitation extremes occurred in the months of July, August, and October, which
      had noticeable adverse effects on rice yield; (2) the maximum 7-day precipitation
      of July and the number of rainy days of August and October should be considered
      as three key indicators for the precipitation-induced rice meteorological
      disasters; and (3) most of the stations showed an increasing trends for the
      maximum 7-day precipitation of July and the number of rainy days of August, while
      the number of rainy days of October in all the stations demonstrated a decreasing
      trend. Moreover, Jiangsu province could be divided into two major sub-regions
      such as north and south areas with different temporal variations in the three key
      indicators.

PMID- 28508259
TI  - Investigation of the scaling characteristics of LANDSAT temperature and
      vegetation data: a wavelet-based approach.
AB  - An investigation of the scaling characteristics of vegetation and temperature
      data derived from LANDSAT data was undertaken for a heterogeneous area in Tamil
      Nadu, India. A wavelet-based multiresolution technique decomposed the data into
      large-scale mean vegetation and temperature fields and fluctuations in
      horizontal, diagonal, and vertical directions at hierarchical spatial
      resolutions. In this approach, the wavelet coefficients were used to investigate
      whether the normalized difference vegetation index (NDVI) and land surface
      temperature (LST) fields exhibited self-similar scaling behaviour. In this study,
      l-moments were used instead of conventional simple moments to understand scaling
      behaviour. Using the first six moments of the wavelet coefficients through five
      levels of dyadic decomposition, the NDVI data were shown to be statistically self
      similar, with a slope of approximately -0.45 in each of the horizontal, vertical,
      and diagonal directions of the image, over scales ranging from 30 to 960 m. The
      temperature data were also shown to exhibit self-similarity with slopes ranging
      from -0.25 in the diagonal direction to -0.20 in the vertical direction over the
      same scales. These findings can help develop appropriate up- and down-scaling
      schemes of remotely sensed NDVI and LST data for various hydrologic and
      environmental modelling applications. A sensitivity analysis was also undertaken
      to understand the effect of mother wavelets on the scaling characteristics of LST
      and NDVI images.

PMID- 28508260
TI  - Sarcoidosis in Israel: Clinical Outcome Status, Organ Involvement, and Long-Term
      Follow-Up.
AB  - PURPOSE: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown
      etiology with heterogeneous outcomes. This study reviewed the clinical outcome
      status (COS) and organ involvement of Israeli sarcoidosis patients during a five
      year period. Further, we compared our results to the 'World Association of
      Sarcoidosis and Other Granulomatous Disease' (WASOG) COS and the 'A Case Control
      Etiologic Study of Sarcoidosis' (ACCESS) instruments in order to evaluate their
      relevance to the Israeli population. METHODS: The retrospective study group
      consisted of 166 sarcoidosis patients for the period of 2010-2015. Data on
      demographic characteristics, presenting symptoms, co-morbidities, disease
      duration, lung function tests, treatment program, chest X-ray, and chest high
      resolution computed tomography were collected. RESULTS: The median patient age
      was 62 +/- 14, which was significantly higher than the WASOG and ACCESS cohorts
      (p < 0.0001), and the average disease duration was 9.8 +/- 7.5 years. Resembling
      the ACCESS cohort, most patients were women (67.5%). The majority of patients
      suffered from constitutional symptoms (86%), as well as from respiratory symptoms
      (38.5%). Similarly to the ACCESS cohort, 91% of patients presented with lung
      involvement. However, significant differences in the involvement of other organs
      were noted, including lymph nodes (3 vs. 15.2%), liver (3.6 vs. 11.5%), CNS (7.2
      vs. 4.6%), and joints (3.6 vs. 0.5%). In addition, significant differences were
      observed in the COS of the Israeli population in comparison to the WASOG data (p
      < 0.01). CONCLUSIONS: Sarcoidosis in Israel is a unique and challenging disease
      with its clinical presentations that differ from previously reported studies.

PMID- 28508262
TI  - ?

PMID- 28508263
TI  - New Insights into the Anatomy of the Midface Musculature and its Implications on
      the Nasolabial Fold.
AB  - BACKGROUND: The prominent nasolabial fold is a distinct feature of the aging
      midface. As minimally invasive procedures have become mainstream,
      chemodenervation is a preferred method for treating dynamic facial rhytids. We
      therefore sought to identify relevant nasolabial fold and midfacial muscular
      anatomy to determine the ideal location of neuromodulation to improve the
      aesthetics of the midface and nasolabial fold without altering the upper lip and
      smile. METHODS: Twelve hemifacial cadaveric dissections were performed to
      identify midface muscle origin, insertion, width, vector of pull, and neighboring
      structures. Attention was focused on the levator labii superioris alaeque nasi
      (LLSAN), levator labii superioris (LLS), nasalis, and orbicularis oculi.
      Measurements were obtained based on surface landmarks including the medial
      canthus for future neurotoxin injection. RESULTS: The LLSAN inserts into the
      medial nasolabial fold and alar base, while the LLS inserts into the middle third
      of the nasolabial fold. The broadest portion of the superior LLSAN was on average
      8.4 mm inferior and 4.6 mm medial to the medial canthus. A separate muscle
      obliquely oriented between the orbicularis oculi and LLSAN was identified and
      found to insert into the malar fat pad. This "malar levator" was present in all
      specimens and has implications on medial periorbital rhytids and the tear trough
      deformity. CONCLUSION: This study further defines midfacial and nasolabial fold
      muscular anatomy and provides new insights into the use of neuromodulators for
      these areas without affecting upper lip position. The malar levator muscle
      appears to be a separate midfacial muscle with independent action. LEVEL OF
      EVIDENCE V: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 28508261
TI  - Functional roles of the pepper leucine-rich repeat protein and its interactions
      with pathogenesis-related and hypersensitive-induced proteins in plant cell death
      and immunity.
AB  - MAIN CONCLUSION: Pepper leucine-rich repeat protein (CaLRR1) interacts with
      defense response proteins to regulate plant cell death and immunity. This review
      highlights the current understanding of the molecular functions of CaLRR1 and its
      interactor proteins. Plant cell death and immune responses to microbial pathogens
      are controlled by complex and tightly regulated molecular signaling networks.
      Xanthomonas campestris pv. vesicatoria (Xcv)-inducible pepper (Capsicum annuum)
      leucine-rich repeat protein 1 (CaLRR1) serves as a molecular marker for plant
      cell death and immunity signaling. In this review, we discuss recent advances in
      elucidating the functional roles of CaLRR1 and its interacting plant proteins,
      and understanding how they are involved in the cell death and defense responses.
      CaLRR1 physically interacts with pepper pathogenesis-related proteins (CaPR10 and
      CaPR4b) and hypersensitive-induced reaction protein (CaHIR1) to regulate plant
      cell death and defense responses. CaLRR1 is produced in the cytoplasm and
      trafficked to the extracellular matrix. CaLRR1 binds to CaPR10 in the cytoplasm
      and CaPR4b and CaHIR1 at the plasma membrane. CaLRR1 synergistically accelerates
      CaPR10-triggered hypersensitive cell death, but negatively regulates CaPR4b- and
      CaHIR1-triggered cell death. CaHIR1 interacts with Xcv filamentous hemagglutinin
      (Fha1) to trigger disease-associated cell death. The subcellular localization and
      cellular function of these CaLRR1 interactors during plant cell death and defense
      responses were elucidated by Agrobacterium-mediated transient expression, virus
      induced gene silencing, and transgenic overexpression studies. CaPR10, CaPR4b,
      and CaHIR1 positively regulate defense signaling mediated by salicylic acid and
      reactive oxygen species, thereby activating hypersensitive cell death and disease
      resistance. A comprehensive understanding of the molecular functions of CaLRR1
      and its interacting protein partners in cell death and defense responses will
      provide valuable information for the molecular genetics of plant disease
      resistance, which could be exploited as a sustainable disease management
      strategy.

PMID- 28508264
TI  - Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin
      Preparation from Human Plasma.
AB  - BACKGROUND: A highly purified 10% liquid intravenous immunoglobulin, IQYMUNE(r),
      has been developed using an innovative manufacturing process including an
      affinity chromatography step for the removal of anti-A and anti-B hemagglutinins.
      OBJECTIVES: The pathogen (viruses and prions) clearance efficacy of the
      manufacturing process and its robustness for critical steps were investigated.
      METHODS: The manufacturing process of IQYMUNE(r) includes two dedicated
      complementary virus reduction steps: solvent/detergent (S/D) treatment and 20 nm
      nanofiltration as well as two contributing steps, namely caprylic acid
      fractionation and anion-exchange chromatography. The clearance capacity and
      robustness of these steps were evaluated with a wide range of viruses (enveloped
      and non-enveloped) and with a model of human transmissible spongiform
      encephalopathies (TSEs). RESULTS: The IQYMUNE(r) manufacturing process
      demonstrated a high and robust virus removal capacity with global reduction
      factors (RFs) of relevant and model viruses: >=14.8 log10 for human
      immunodeficiency virus type 1 (HIV-1), >=16.9 log10 for bovine viral diarrhoea
      virus (BVDV)/Sindbis virus, >=15.7 log10 for pseudorabies virus (PRV), >=12.8
      log10 for encephalomyocarditis virus (EMCV) and 11.0 log10 for porcine parvovirus
      (PPV). The process also exhibited a high removal capacity for the TSE agent with
      an overall RF of >=12.9 log10 due to the complementary actions of the caprylic
      acid fractionation, anion-exchange chromatography and nanofiltration steps.
      CONCLUSION: Data from virus and prion clearance studies fully support the high
      safety profile of IQYMUNE(r), with a minimal reduction of 11 log10 for the
      smallest and most resistant non-enveloped virus, PPV, and more than 12 log10 for
      the TSE agent.

PMID- 28508265
TI  - Incidence of Vertebral Fractures in Women with Systemic Lupus Erythematosus After
      8 Years of Follow-Up.
AB  - The aim of this study was to evaluate possible associations between potential
      risk factors and the occurrence of established vertebral fractures (VF) in
      Mexican patients with systemic lupus erythematosus (SLE). Consecutive patients
      with SLE were enrolled in a prospective, observational study from 2006 to 2015.
      Information on potential risk factors, including demographics, clinical data, and
      bone mineral density (BMD) at the lumbar spine and hip on dual-energy X-ray
      absorptiometry was collected at baseline and follow-up. Semiquantitative analysis
      was used to determine incident VF on lateral thoracic and lumbar radiographs,
      defined as any vertebral body graded normal at baseline and at least mildly
      deformed (20-25% reduction or more in any vertebral height) during follow-up.
      Differences in baseline characteristics were assessed in patients with and
      without new radiographic VF. Of 110 SLE patients included, with a median follow
      up of 8 (IQR 8-9) years, 22 (20%) had radiographic VF at baseline; 35 (32%)
      patients had a new VF. The annual incidence rate of new morphometric VF was 3.5
      (95% CI 2.4-4.91) per 100 patient/years. Most fractures were mild or moderate and
      biconcave shaped. Incident VF were significantly associated with baseline BMD at
      the total hip and longer disease duration. Cumulative glucocorticoid dose,
      postmenopausal status, and previous prevalent VF were not associated with VF. In
      this SLE cohort in daily clinical practice, new VF were frequently present in SLE
      patients, especially those with longer disease duration and low-hip BMD.

PMID- 28508266
TI  - The combined association of alcohol consumption with dementia risk is likely
      biased due to lacking account of death cases.

PMID- 28508267
TI  - Will it be cheese, bologna, or peanut butter?

PMID- 28508268
TI  - Regadenoson stress during low-level exercise: The EXERRT trial-does it move the
      needle?

PMID- 28508269
TI  - Erratum to: Guidelines in review: Comparison between AHA/ACC and ESC guidelines
      for the management of patients with ventricular arrhythmias and the prevention of
      sudden cardiac death.

PMID- 28508270
TI  - The impact of combined cardiopulmonary exercise testing and SPECT myocardial
      perfusion imaging on downstream evaluation and management.
AB  - OBJECTIVE: The diagnostic yield of combined cardiopulmonary exercise testing
      (CPET) and myocardial perfusion imaging (MPI) in patients referred for stress
      testing has received limited study. METHODS: We evaluated consecutive patients
      who underwent combined CPET-MPI at a single tertiary referral center between 2011
      and 2015. An abnormal CPET was defined as any of the following: reduced oxygen
      consumption, cardiac output impairment, or pulmonary impairment. Normal MPI was
      defined as the absence of resting or stress perfusion defect. The primary study
      outcome was change in clinical decision-making after CPET-MPI including
      management of pulmonary disease, management of deconditioning, heart failure
      management, and referral for cardiac catheterization. Outcomes of patients with
      normal and abnormal MPI were presented based on the specific CPET abnormality.
      RESULTS: 415 patients were included in the study. Of the 269 patients that had
      normal MPI, 206 (77%) had abnormal CPET. Patients with abnormal CPET and normal
      MPI, compared with patients that had normal CPET and normal MPI, were more
      frequently diagnosed with pulmonary disease (11.7% vs 3.2%, P = .04) and
      deconditioning (33.5% vs 17.4%, P = .01). Of the 146 patients that had abnormal
      MPI, 128 (88%) had abnormal CPET. Patients with abnormal CPET and abnormal MPI,
      compared with patients that had normal CPET and abnormal MPI, did not
      statistically differ with regard to the study outcome. CONCLUSION: An abnormal
      CPET, if the MPI was normal, prompted further evaluation and led to management of
      pulmonary disease and deconditioning.

PMID- 28508271
TI  - Optimization of temporal sampling for 82rubidium PET myocardial blood flow
      quantification.
AB  - BACKGROUND: Suboptimal temporal sampling of left ventricular (LV) blood pool and
      tissue time-activity curves (TACs) may introduce bias and increased variability
      in estimates of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic
      PET myocardial perfusion images. We aimed to optimize temporal sampling for
      estimation of MBF and MFR. METHODS: Twenty-four normal volunteers and 32 patients
      underwent dynamic stress/rest rubidium-82 chloride (82Rb) PET imaging. Fine
      temporal sampling was used to estimate the full width at half maximum (FWHM) of
      the LV blood pool TAC. Fourier analysis was used to determine the longest
      sampling interval, T S, as a function of FWHM, which preserved the information
      content of the blood phase. Dynamic datasets were reconstructed with frame
      durations varying from 2 to 20 seconds over the first 2 minutes for the blood
      phase and 30 to 120 seconds for the tissue phase. The LV blood pool and tissue
      TACs were sampled using regions of interest (ROI) and fit to a compartment model
      for quantification of MBF and MFR. The effects of temporal sampling on MBF and
      MFR were evaluated using clinical data and simulations. RESULTS: T S increased
      linearly with input function FWHM (R = 0.93). Increasing the blood phase frame
      duration from 5 to 15 seconds resulted in MBF and MFR biases of 6-12% and
      increased variability of 14-24%. Frame durations <5 seconds had biases of less
      than 5% for both MBF and MFR values. Increasing the tissue phase frame durations
      from 30 to 120 seconds resulted in <5% biases. CONCLUSIONS: A two-phase framing
      of dynamic 82Rb PET images with frame durations of 5 seconds (blood phase) and
      120 seconds (tissue phase) optimally samples the blood pool TAC for modern 3D PET
      systems.

PMID- 28508272
TI  - Nasopharyngeal Angiofibroma: A Clinical, Histopathological and
      Immunohistochemical Study of 42 Cases with Emphasis on Stromal Features.
AB  - Nasopharyngeal angiofibroma is a benign but aggressive tumor of unknown etiology,
      typically occurring in adolescent males. It is described as a rare neoplasm;
      however, the prevalence seems to have geographic differences. All cases referred
      to our head and neck clinical and pathology service were reviewed. Most of the
      patients presented at an advanced stage. The clinical and radiographic features
      are presented and discussed. Histologically, the tumor shows a highly vascular
      fibrous proliferation with characteristic plump, angulated and stellate cells,
      categorized as fibroblasts. Immunohistochemistry was performed on 42 cases to
      further elucidate the nature of these cells. The stromal cells expressed vimentin
      and factor XIIIa, the latter expressed most commonly in the giant stellate cells.
      Inflammation was almost exclusively present in peripheral subepithelial areas.
      Mast cells were abundant, even in the absence of other inflammatory cells.
      Lymphatics were observed principally in peripheral regions. Proliferating cells
      (Ki-67 reactive) were restricted to endothelial cells.

PMID- 28508274
TI  - The Sleeping Remnant. Effect of Roux-En-Y Gastric Bypass on Plasma Levels of
      Gastric Biomarkers in Morbidly Obese Women: A Prospective Longitudinal Study.
AB  - BACKGROUND: Morpho-functional modifications of the gastric remnant after Roux-en
      Y gastric bypass (RYGB) have not been completely defined, due to its
      inaccessibility for bioptic mapping. The aim of the study is to evaluate such
      modifications using Gastropanel(r), a non-invasive blood test cross-checking four
      gastric biomarkers, able to provide a snapshot of mucosa conditions. SUBJECTS AND
      METHODS: Twenty-four women undergoing RYGB were prospectively enrolled.
      Gastropanel(r) parameters (pepsinogens, Gastrin-17 and immunoglobulins against
      Helicobacter pylori), biometrical/clinical data were collected preoperatively and
      at 6-months follow-up. RESULTS: All parameters showed significant reduction (p <
      0.05). Pepsinogen I reduction correlated with BMI percent decrease. CONCLUSIONS:
      The exclusion of food transit is responsible for significant drop in gastric
      output, hardly representing a risk factor in the remnant carcinogenesis, being
      unexposed to alimentary carcinogenic agents.

PMID- 28508273
TI  - Sleeve Gastrectomy: Correlation of Long-Term Results with Remnant Morphology and
      Eating Disorders.
AB  - BACKGROUND: Remnant dimension is considered one of the crucial elements
      determining the success of sleeve gastrectomy (SG), and dilation of the gastric
      fundus is often believed to be the main cause of failure. OBJECTIVES: The main
      outcome of this study is to find correlations between remnant morphology in the
      immediate post-operative stage, its dilation in years, and the long-term results.
      The second purpose aims to correlate preoperative eating disorders, taste
      alteration, hunger perception, and early satiety with post-SG results. MATERIALS
      AND METHODS: Remnant morphology was evaluated, in the immediate post-operative
      stage and over the years (>=2 years), through X-ray of the oesophagus-stomach
      duodenum calculating the surface in anteroposterior (AP) and right anterior
      oblique projection (RAO). Presurgery diagnosis of eating disorders and their
      evaluation through "Eating Disorder Inventory-3" (EDI3) during follow-up were
      performed. Change in taste perception, sense of appetite, and early satiety were
      evaluated. Patients were divided into two groups: "failed SGs (EWL<50%) and
      "efficient SGs" (EWL >50%). RESULTS: There were a total of 50 patients (37 F, 13
      M), with mean age 52 years, preoperative weight 131 +/- 21.8 kg, and BMI 47.4 +/-
      6.8 kg/m2. Post-operative remnant mean dimensions overlapped between the two
      groups. On a long-term basis, an increase of 57.2 and 48.4% was documented in the
      AP and RAO areas respectively. In "failed" SGs, dilation was significantly
      superior to "efficient" SGs (AP area 70.2 vs 46.1%; RAO area 59.3 vs 39%; body
      width 102% vs 41.7%). Preoperative eating disorders were more present in
      efficient SGs than in failed SGs with the exception of sweet eating. There were
      no significant changes to taste perception during follow-up. Fifty-two percent of
      efficient SGs vs 26% of failed SGs reported a persistent lack of sense of hunger;
      similarly, 92.5 vs 78% declared the persistence of a sense of early satiety. The
      two groups did not statistically differ as far as all the variables of the EDI3
      are concerned. CONCLUSION: On a long-term basis, the remnant mean dilation is
      around 50% compared to the immediate post-operative stage but failed SGs showed
      larger remnant dilation than efficient SGs and, in percentage, the more dilated
      portion is the body of the stomach. As far as all the EDI3 variables obtained are
      concerned, the two groups did not statistically differ. Of all eating disorders,
      sweet eating seems to be weakly connected to SG failure.

PMID- 28508275
TI  - Gross Olfaction Before and After Laparoscopic Gastric Bypass.
AB  - BACKGROUND: Obesity leads to olfaction alterations, and this can further impact
      food choices, appetite, and nutritional status. Bariatric procedures induce
      weight loss and change in taste and smell perception, but more information is
      needed, especially using objective olfaction tests. METHODS: A prospective study
      was conducted during 6 months, with candidates to laparoscopic gastric bypass at
      a single institution. A preoperative nasofibroscopy and gross smell
      identification test (The Pocket Smell Test (r)) were performed in those meeting
      the inclusion criteria. After 6 months, a new test was performed, and the primary
      objective was to determine if there was an improvement in the olfaction score.
      Weight loss and comorbidities improvement were also analyzed. RESULTS: From the
      30 patients with morbid obesity enrolled, 21 met the inclusion criteria and ENT
      evaluation. At baseline, 42.8% of patients scored 3 points, 53.3% scored 2
      points, and 4.7% scored 1 point. After 6 months, there was a -81.1% of change.
      Seventeen patients scored 3 points (p = 0.002 vs initial) and two scored 2 points
      (p = 0.006 vs initial). There were no patients with less than 2 points. Weight
      and comorbidities had a significant improvement as well. CONCLUSION: Laparoscopic
      gastric bypass improves the olfaction scores of the Pocket Smell Test in morbidly
      obese patients 6 months after their procedure. More complex tests can be used in
      candidates to bariatric surgery if low scores are detected initially. Other
      causes of olfaction dysfunctions should be determined if there is no improvement
      after weight loss.

PMID- 28508276
TI  - Effects of Sleeve Gastrectomy on Serum 12alpha-Hydroxylated Bile Acids in a
      Diabetic Rat Model.
AB  - BACKGROUND: Diabetes mellitus is a prevalent disease that endangers human health.
      Bariatric surgery can effectively relieve insulin resistance with elevated serum
      bile acids (BAs). 12alpha-Hydroxylated BAs were previously reported to be
      associated with insulin resistance. The aim of this study was to analyze changes
      in 12alpha-hydroxylated BA composition and possible associated mechanisms in
      diabetic rats following sleeve gastrectomy (SG). METHODS: SG and sham operations
      were performed in diabetic rats induced by high-fat diet feeding and
      streptozotocin. Body weight, food intake, oral glucose tolerance test (OGTT),
      insulin tolerance test (ITT), and serum BAs were analyzed at corresponding time
      points. Cholesterol 12alpha-hydroxylase (CYP8B1) and transcription factor V-Maf
      Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog G (MAFG) expression levels
      were assessed by RT-PCR and western blotting. RESULTS: Compared with the SHAM
      group, the SG group displayed significant weight loss from 6 weeks
      postoperatively, accompanied by decreased food intake from 4 weeks after the
      operation. At 2 and 12 weeks postoperatively, the areas under the curve of OGTT
      and ITT were significantly decreased in the SG group. At 12 weeks post-operation,
      the SG group displayed elevated serum BAs, but the percentage of 12alpha
      hydroxylated BAs was reduced. Furthermore, SG rats exhibited higher MAFG and
      lower CYP8B1 protein and mRNA levels in the liver (P < 0.05). CONCLUSION: The
      percentage of 12alpha-hydroxylated bile acids was reduced after SG, which was
      relevant with the inhibition of CYP8B1 and overexpression of MAFG. These outcomes
      may play an important role in the improvement of insulin sensitivity following
      SG.

PMID- 28508277
TI  - Surgical Management of Obesity Among People with Schizophrenia and Bipolar
      Disorder: a Systematic Review of Outcomes and Recommendations for Future
      Research.
AB  - BACKGROUND: People with schizophrenia or bipolar disorder (BD) exhibit very high
      levels of obesity. Little is known about the potential benefits/risks of obesity
      surgery. We conducted a narrative review to summarize the available knowledge on
      bariatric surgery in people with schizophrenia or BD. METHODS: A systematic
      search was conducted of major electronic databases from inception to October 2016
      for studies investigating bariatric surgery among people with schizophrenia or
      BD. Data were presented in a narrative synthesis and future research strategies
      proposed. RESULTS: The electronic database searches identified 44 records. Eight
      studies (BD, n = 265; schizophrenia: n = 14) were included with a mean study
      length of 15.7 months (12-24). Seven found that bariatric surgery resulted in
      weight loss in those with psychiatric disorders with an excess weight loss
      ranging -31 to -70%. Six studies found that weight loss from bariatric surgery
      was similar in people with schizophrenia or BD versus controls. However, most of
      the studies limited their outcomes to only weight loss and did not measure
      whether obesity surgery affected the status and treatment of psychiatric
      symptoms. Although few adverse events were reported among patients with BD, data
      from two studies demonstrated no significant deterioration of psychiatric
      symptoms post-surgery in people with schizophrenia. CONCLUSIONS: Growing evidence
      suggests that bariatric surgery may improve short-term weight status among people
      with BD. However, given the paucity of studies for schizophrenia, and the lack of
      information on medium-to long-term results, future large-scale high-quality
      studies are required.

PMID- 28508279
TI  - The coexistence of both replaced proper hepatic and gastroduodenal arteries due
      to the common hepatic artery absence.
AB  - Anatomical variants of the celiac trunk (CT) branches and especially these of
      hepatic arteries (HAs) are among the most common variants of the arterial tree.
      The knowledge of the wide variability in hepatic arterial supply is of paramount
      importance in hepatobiliary, pancreatic, gastric, and esophageal surgery, as well
      as in liver transplantations. The purpose of this case report is to describe a
      rare variant discovered during abdominal dissection of a 74-year-old male cadaver
      of Greek origin, in which the common hepatic artery was absent and its branches,
      the proper hepatic artery (PHA) and the gastroduodenal artery (GDA) had an
      aberrant and separate origin. The entire arterial supply to the liver derived
      from the aberrant PHA, that originating from the superior mesenteric artery and
      was named as PHA (RPHA). The RPHA, after a course posterior to the portal vein,
      terminated into the right and left HAs, at the hilum. The GDA originated from the
      CT, as well as the left gastric and splenic artery. The right gastric artery
      originated from the PHA, as usual. The current case emphasizes the necessity of
      preoperative imaging when evaluating the resectability of a tumor in
      hepatobiliary and pancreatic area taking into account the possible vascular
      variations. Abdominal surgeon should be aware of any aberrancy to avoid potential
      iatrogenic injury and lethal complications.

PMID- 28508278
TI  - Physiotherapy programme reduces fatigue in patients with advanced cancer
      receiving palliative care: randomized controlled trial.
AB  - PURPOSE: Cancer-related fatigue (CRF) is a common and relevant symptom in
      patients with advanced cancer that significantly decreases their quality of life.
      The aim of this study was to evaluate the effect of a physiotherapy programme on
      CRF and other symptoms in patients diagnosed with advanced cancer. METHODS: The
      study was designed as a randomized controlled trial. Sixty patients diagnosed
      with advanced cancer receiving palliative care were randomized into two groups:
      the treatment group (n = 30) and the control group (n = 30). The therapy took
      place three times a week for 2 weeks. The 30-min physiotherapy session included
      active exercises, myofascial release and proprioceptive neuromuscular
      facilitation (PNF) techniques. The control group did not exercise. The outcomes
      included Brief Fatigue Inventory (BFI), Edmonton Symptom Assessment Scale (ESAS)
      and satisfaction scores. RESULTS: The exercise programme caused a significant
      reduction in fatigue scores (BFI) in terms of severity of fatigue and its impact
      on daily functioning. In the control group, no significant changes in the BFI
      were observed. Moreover, the physiotherapy programme improved patients' general
      well-being and reduced the intensity of coexisting symptoms such as pain,
      drowsiness, lack of appetite and depression. The analysis of satisfaction scores
      showed that it was also positively evaluated by patients. CONCLUSION: The
      physiotherapy programme, which included active exercises, myofascial release and
      PNF techniques, had beneficial effects on CRF and other symptoms in patients with
      advanced cancer who received palliative care. The results of the study suggest
      that physiotherapy is a safe and effective method of CRF management.

PMID- 28508280
TI  - Treatment of spondylodiscitis after rectopexy: surgery is always required
      Fauheron JL, Trilling B.

PMID- 28508281
TI  - Perineal hernia repair after abdominoperineal excision or extralevator
      abdominoperineal excision: a systematic review of the literature.
AB  - BACKGROUND: The incidence of perineal hernia after abdominoperineal excision and
      extralevator abdominoperineal excision ranges from 1 to 26%. In this systematic
      review, we compared surgical options and postoperative outcomes of perineal
      hernia repair in this setting from 2012 to 2016 with findings in a review of
      publications 1944-2011. METHODS: We searched the PubMed database using the
      keywords "hernia" AND "perineum" identified 392 papers published from 1946 to
      2016. Two hundred and ninety-six papers published before 2012 were excluded and
      96 were found to be potentially relevant. RESULTS: Twenty-one studies with a
      total of 108 patients were included in the final analysis. Perineal hernia repair
      was performed using the perineal approach in 75 patients (69.44%), the
      laparoscopic approach in 25 patients (23.14%), the open abdominal approach in
      three patients (2.77%) and the laparoscopic perineal approach in three patients
      (2.77%) and the open abdominoperineal approach in two patients (1.8%). Non
      absorbable mesh was used in 41 (37.96%) of cases, composite mesh in 20 (18.51%)
      and biological mesh in 19 (17.59%). Flap reconstruction was used in 25 patients
      (23.14%). First and second recurrences were observed in 26 (24.07%) and 7
      (26.92%) cases, respectively. CONCLUSIONS: Comparison of perineal hernia repair
      from 1944 to 2011 and from 2012 to 2016 showed that perineal and laparoscopic
      approaches are currently the most commonly used techniques. Primary defect
      closure was abandoned in favor of synthetic or composite mesh placement. Use of
      flap reconstruction spread rapidly and the recurrence rate was low. Randomized
      control trials and a larger sample size are needed to confirm these data and to
      develop a gold standard treatment for secondary hernia repair after
      abdominoperineal excision or extralevator abdominoperineal excision.

PMID- 28508283
TI  - Young adults self-derive and retain new factual knowledge through memory
      integration.
AB  - The present research investigated the retention of new factual knowledge derived
      through integration of information acquired across temporally distributed
      learning episodes. Young adults were exposed to novel facts as they read long
      lists of seemingly unrelated information, one sentence at a time. They then were
      presented open-ended questions, the answers to which could be self-derived
      through integration of pairs of facts from the list. Experiment 1 was the first
      test of self-derivation of new factual knowledge through integration in adults
      using open-ended testing (as opposed to forced-choice testing). Participants
      successfully self-derived integrated knowledge under these more challenging
      conditions. Experiment 2 was a test for long-term retention of newly self-derived
      information. Newly derived knowledge remained accessible after a 1-week delay.
      Striking individual differences were also observed, which were related to whether
      individuals spontaneously identified the relational structure of the learning
      task. Insight into the relation between explicit task knowledge and strategic
      processing was also revealed through examination of response speed at the time of
      test. Specifically, knowledge of the task structure was associated with response
      latencies on unsuccessful (but not successful) trials, such that participants who
      were aware of the opportunity to integrate spent longer when they were
      subsequently unsuccessful, presumably reflecting directed search strategies and
      heightened perseverance when those processes failed. Together, the present
      findings provide direct evidence for the role of memory integration in the long
      term accumulation of a semantic knowledge base and have theoretical implications
      for our understanding of this fundamental form of learning.

PMID- 28508282
TI  - Malignancy Incidence, Management, and Prevention in Patients with Rheumatoid
      Arthritis.
AB  - Traditional and biologic disease-modifying antirheumatic drugs (DMARDs) are
      effective medications for the management of rheumatoid arthritis (RA). However,
      the effects of these medications on immune function raises concern that they may
      increase long-term cancer risk. The baseline risk for some cancers appears to
      differ in patients with RA compared to the general population, with the former
      having an increased risk of lymphoma, lung cancer and renal cancer, but a
      decreased risk of colorectal and breast cancer. Some DMARDs appear to increase
      the rate of specific cancer types (such as bladder cancer with cyclophosphamide),
      but few appear to increase the overall cancer risk. Studying the link between
      lymphoma and disease severity in RA is complicated because patients with
      persistently active disease are at increased risk for lymphoma, and disease
      severity correlates with more intense use of immunosuppressive medications.
      Overall, cancer risk in patients with RA is slightly above that of the general
      population, with the increased risk likely secondary to an increased risk of
      lymphomas in those with high disease activity. Risk mitigation includes
      management of RA disease activity as well as age- and sex-appropriate cancer
      screening.

PMID- 28508285
TI  - Flame Atmospheric Pressure Chemical Ionization Coupled with Negative Electrospray
      Ionization Mass Spectrometry for Ion Molecule Reactions.
AB  - Flame atmospheric pressure chemical ionization (FAPCI) combined with negative
      electrospray ionization (ESI) mass spectrometry was developed to detect the
      ion/molecule reactions (IMRs) products between nitric acid (HNO3) and negatively
      charged amino acid, angiotensin I (AI) and angiotensin II (AII), and insulin
      ions. Nitrate and HNO3-nitrate ions were detected in the oxyacetylene flame,
      suggesting that a large quantity of nitric acid (HNO3) was produced in the flame.
      The HNO3 and negatively charged analyte ions produced by a negative ESI source
      were delivered into each arm of a Y-shaped stainless steel tube where they merged
      and reacted. The products were subsequently characterized with an ion trap mass
      analyzer attached to the exit of the Y-tube. HNO3 showed the strongest affinity
      to histidine and formed (Mhistidine-H+HNO3)- complex ions, whereas some amino
      acids did not react with HNO3 at all. Reactions between HNO3 and histidine
      residues in AI and AII resulted in the formation of dominant [MAI-H+(HNO3)]- and
      [MAII-H+(HNO3)]- ions. Results from analyses of AAs and insulin indicated that
      HNO3 could not only react with basic amino acid residues, but also with disulfide
      bonds to form [M-3H+(HNO3)n]3- complex ions. This approach is useful for
      obtaining information about the number of basic amino acid residues and disulfide
      bonds in peptides and proteins. Graphical Abstract ?.

PMID- 28508284
TI  - Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical
      tumour and specific bone remodelling markers in prostate cancer bone metastases.
AB  - PURPOSE: 18F-fluoride PET/CT exhibits high sensitivity to delineate and measure
      the extent of bone metastatic disease in patients with prostate cancer. 18F
      fluoride PET/CT could potentially replace traditional bone scintigraphy in
      clinical routine and trials. However, more studies are needed to assess
      repeatability and biological uptake variation. The aim of this study was to
      perform test-retest analysis of quantitative PET-derived parameters and
      blood/serum bone turnover markers at the same time point. Ten patients with
      prostate cancer and verified bone metastases were prospectively included. All
      underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five
      dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were
      recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and
      functional tumour volume applying a VOI with 50% threshold (FTV50%). The total
      skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a
      threshold of SUV of >=15. Blood/serum biochemical bone turnover markers obtained
      at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP.
      RESULTS: A total of 47 index lesions and a range of 2-122 bone metastases per
      patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range
      6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV50%
      for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical
      bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin
      18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. CONCLUSIONS: Quantitative 18F-fluoride
      uptake and simultaneous biochemical bone markers measurements are reproducible
      for prostate cancer metastases and show similar magnitude in test-retest
      variation.

PMID- 28508286
TI  - Sample Preparation of Corn Seed Tissue to Prevent Analyte Relocations for Mass
      Spectrometry Imaging.
AB  - Corn seed tissue sections were prepared by the tape support method using an
      adhesive tape, and mass spectrometry imaging (MSI) was performed. The effect of
      heat generated during sample preparation was investigated by time-of-flight
      secondary mass spectrometry (TOF-SIMS) imaging of corn seed tissue prepared by
      the tape support and the thaw-mounted methods. Unlike thaw-mounted sample
      preparation, the tape support method does not cause imaging distortion because of
      the absence of heat, which can cause migration of the analytes on the sample. By
      applying the tape-support method, the corn seed tissue was prepared without
      structural damage and MSI with accurate spatial information of analytes was
      successfully performed. Graphical Abstract ?.

PMID- 28508287
TI  - [Pathology of familial tumor syndromes].

PMID- 28508288
TI  - Repetitive postoperative extubation failure and cardiac arrest due to
      laryngomalacia after general anesthesia in an elderly patient: a case report.
AB  - The authors report a case involving an elderly patient who experienced repetitive
      perioperative cardiac arrest caused by laryngomalacia. The patient underwent
      surgery under general anesthesia; however, 2 h after initial extubation, he
      experienced cardiopulmonary arrest. Return of spontaneous circulation was
      achieved by immediate resuscitation. Four hours later, a second extubation was
      performed without any neurological complications. However, 2 h later, he
      experienced cardiopulmonary arrest again. Immediately after the third extubation,
      12 h after the second cardiopulmonary arrest, fiberoptic laryngoscopy revealed
      laryngomalacia. His respiratory condition stabilized after emergent tracheostomy.
      Laryngomalacia should be considered even in adult cases when signs of upper
      airway obstruction manifest after extubation.

PMID- 28508289
TI  - Somatic mosaicism with reversion to normality of a mutated transthyretin allele
      related to a familial amyloidotic polyneuropathy.
AB  - Familial amyloidotic polyneuropathy (FAP) is a progressive neuropathy, with onset
      in adulthood and high mortality. It is related to an altered transthyretin (TTR)
      plasma protein, mainly produced by the liver and responsible for amyloid deposit
      in the peripheral nervous system. SNPs in the TTR gene were associated with FAP,
      and the G>C substitution (NM_000371.3:c.325G>C) in the 109th codon (GAG vs CAG;
      NP_362.1:p.E109Q) was previously described in Sicily (Italy). Here, we report on
      a Sicilian family with several patients affected by FAP related to the E109Q
      mutation, which displayed a somatic mosaicism with the reversion to normality of
      the c.325G>C mutation. After exclusion of isodisomy and allele deletion, this
      event seems to be due to a rare, post-zygotic interallelic gene conversion with
      the wild-type allele serving as a donor. Further investigations will be necessary
      to better understand the molecular basis of this phenomenon, and could help
      determine if this can be induced in a targeted manner in the context of natural
      gene therapy to treat TTR-related FAP patients, as previously proposed for other
      diseases. Moreover, our results confirm the need to perform DNA-based diagnostic
      tests with at least a second tissue when a suspected germline mutation in a
      candidate gene is not identified in the first tissue.

PMID- 28508292
TI  - Prof. Dr. Kurt Jellinger: an appreciation.

PMID- 28508290
TI  - CRISPR/Cas9-mediated somatic and germline gene correction to restore hemostasis
      in hemophilia B mice.
AB  - Hemophilia B (HB) is an X-linked disorder caused by defects of F9 encoded
      coagulation factor IX, which is an ideal model for gene therapy. Most existing HB
      gene therapies are based on viral mediated gene supplementation, which could
      increase immunoreaction. In this study, CRISPR/Cas9 system was used for gene
      correction in an F9 mutant HB mouse model in both adult mice (in vivo) and in
      germline cells (ex vivo). In vivo, naked Cas9-sgRNA plasmid and donor DNA were
      delivered to HB mice livers to recover the mutation via hydrodynamic tail vein
      (HTV) injection. 62.5% of the HTV-treated mice showed a detectable gene
      correction (>1%) in the F9 alleles of hepatocytes, which was sufficient to remit
      the coagulation deficiency. Ex vivo, three different forms of Cas9 were
      microinjected into germline cells of HB mice to investigate their efficiency and
      safety in gene correction. Cas9 protein showed higher gene recovery rates, less
      embryo toxicity, and lower mosaic repair percentage, making it more suitable for
      germline gene therapy. Our study strongly supports that CRISPR/Cas9-mediated
      genome editing is feasible in gene therapy of genetic disorders.

PMID- 28508291
TI  - Lobular homology in cerebellar hemispheres of humans, non-human primates and
      rodents: a structural, axonal tracing and molecular expression analysis.
AB  - Comparative neuroanatomy provides insights into the evolutionary functional
      adaptation of specific mammalian cerebellar lobules, in which the lobulation
      pattern and functional localization are conserved. However, accurate
      identification of homologous lobules among mammalian species is challenging. In
      this review, we discuss the inter-species homology of crus I and II lobules which
      occupy a large volume in the posterior cerebellar hemisphere, particularly in
      humans. Both crus I/II in humans are homologous to crus I/II in non-human
      primates, according to Paxinos and colleagues; however, this area has been
      defined as crus I alone in non-human primates, according to Larsell and Brodal.
      Our neuroanatomical analyses in humans, macaques, marmosets, rats, and mice
      demonstrate that both crus I/II in humans are homologous to crus I/II or crus I
      alone in non-human primates, depending on previous definitions, and to crus I
      alone in rodents. Here, we refer to the region homologous to human crus I/II
      lobules as "ansiform area (AA)" across animals. Our results show that the AA's
      olivocerebellar climbing fiber and Purkinje cell projections as well as aldolase
      C gene expression patterns are both distinct and conserved in marmosets and
      rodents. The relative size of the AA, as represented by the AA volume fraction in
      the whole cerebellum was 0.34 in human, 0.19 in macaque, and approximately 0.1 in
      marmoset and rodents. These results indicate that the AA reflects an
      evolutionarily conserved structure in the mammalian cerebellum, which is
      characterized by distinct connectivity from neighboring lobules and a massive
      expansion in skillful primates.

PMID- 28508294
TI  - Preoperative MRI is helpful but not sufficient to detect associated lesions in
      patients with chronic ankle instability.
AB  - PURPOSE: The aim of this study was to determine the reliability and validity of
      preoperative magnetic resonance imaging (MRI) scans for the detection of
      additional pathologies in patients with chronic ankle instability (CAI) compared
      to arthroscopic findings. METHODS: Preoperative MRI images of 30 patients were
      evaluated regarding articular and periarticular comorbidities and compared to
      intraoperative findings. The reliability of MRI was determined by calculating
      specificity, sensitivity, as well as positive and negative predictive values. The
      accuracy of the classification of cartilage lesions by Outerbridge and Berndt and
      Harty rating scales was determined by calculating the area under the receiver
      operating curve (AUC). RESULTS: In total, 72 additional pathologies were found
      arthroscopically compared to 73 lesions gathered from MRI images. Sensitivity
      ranged from 89% for peroneal tendinopathy to 28% for additional ligamentous
      lesions. Specificity ranged from 100% for anterolateral impingement, loose bodies
      and peroneal tendinopathy to 38% for additional ligamentous lesions. For
      cartilage lesions, sensitivity was at 91% and specificity was at 55% for the
      Outerbridge grading scale. For the Berndt and Harty classification system,
      sensitivity was at 91% and specificity was at 28%. Correlation of additional
      pathologies ranged from weak (r s = 0.48; p = 0.02) to moderate results (r s =
      0.67; p < 0.001). CONCLUSION: CAI is associated with a high incidence of
      additional pathologies. In some cases, MRI delivers insufficient results, which
      may lead to misinterpretation of present comorbidities. MRI is a helpful tool for
      preoperative evaluation, but arthroscopy remains gold standard in the diagnosis
      of associated lesions in patients with CAI. LEVEL OF EVIDENCE: III.

PMID- 28508295
TI  - MRI-based tendon bone healing is related to the clinical functional scores at the
      first year after anterior cruciate ligament reconstruction with hamstring tendon
      autograft.
AB  - PURPOSE: The correlation between tendon bone healing and clinical functional
      scores after anterior cruciate ligament reconstruction (ACLR) using four-stranded
      hamstring tendon autograft has rarely being reported. The purpose of this study
      was to determine the correlation between magnetic resonance imaging (MRI)-based
      tendon bone healing and clinical functional scores after ACLR using hamstring
      tendon. METHODS: Thirty-eight patients with ACLR using four-stranded hamstring
      tendon autograft were included in this prospective study in the authors' hospital
      from 2013 to 2014. All patients were performed Tegner, Lysholm, International
      Knee Documentation Committee (IKDC) subjective scores, KT-1000 and MRI
      examinations in 3, 6, 12 months after the operation, respectively. According to
      MRI, the healing degree of tendon bone was divided into five grades, and the
      healing degree of the tendon at different time points was evaluated. Moreover,
      the correlations between the clinical scores and tendon bone healing level at 12
      months after the operation were determined. RESULTS: The Tegner, Lysholm, and
      IKDC scores of all patients were gradually improved over time after ACLR, and the
      degree of tendon bone healing was gradually increased. Moreover, there were
      significantly positive correlations between the level of tendon bone healing and
      the clinical functional scores at 12 months after the operation. CONCLUSION: The
      clinical functional scores and the degree of tendon bone healing were gradually
      improved over time after ACLR. Moreover, there were significant positive
      correlations between the level of tendon bone healing and clinical functional
      scores of knee joint at the first year after the operation. LEVEL OF EVIDENCE:
      III.

PMID- 28508293
TI  - Influenza infection and heart failure-vaccination may change heart failure
      prognosis?
AB  - The interaction of influenza infection with the pathogenesis of acute heart
      failure (AHF) and the worsening of chronic heart failure (CHF) is rather complex.
      The deleterious effects of influenza infection on AHF/CHF can be attenuated by
      specific immunization. Our review aimed to summarize the efficacy, effectiveness,
      safety, and dosage of anti-influenza vaccination in HF. In this literature
      review, we searched MEDLINE and EMBASE from January 1st 1966 to December 31st,
      2016, for studies examining the association between AHF/CHF, influenza
      infections, and anti-influenza immunizations. We used broad criteria to increase
      the sensitivity of the search. HF was a prerequisite for our search. The search
      fields used included "heart failure," "vaccination," "influenza," "immunization"
      along with variants of these terms. No restrictions on the type of study design
      were applied. The most common clinical scenario is exacerbation of pre-existing
      CHF by influenza infection. Scarce evidence supports a potential positive
      association of influenza infection with AHF. Vaccinated patients with pre
      existing CHF have reduced all-cause morbidity and mortality, but effects are not
      consistently documented. Immunization with higher antigen quantity may confer
      additional protection, but such aggressive approach has not been generally
      advocated. Further studies are needed to delineate the role of influenza
      infection on AHF/CHF pathogenesis and maintenance. Annual anti-influenza
      vaccination appears to be an effective measure for secondary prevention in HF.
      Better immunization strategies and more efficacious vaccines are urgently
      necessary.

PMID- 28508296
TI  - Modeling the Fear Effect in Predator-Prey Interactions with Adaptive Avoidance of
      Predators.
AB  - Recent field experiments on vertebrates showed that the mere presence of a
      predator would cause a dramatic change of prey demography. Fear of predators
      increases the survival probability of prey, but leads to a cost of prey
      reproduction. Based on the experimental findings, we propose a predator-prey
      model with the cost of fear and adaptive avoidance of predators. Mathematical
      analyses show that the fear effect can interplay with maturation delay between
      juvenile prey and adult prey in determining the long-term population dynamics. A
      positive equilibrium may lose stability with an intermediate value of delay and
      regain stability if the delay is large. Numerical simulations show that both
      strong adaptation of adult prey and the large cost of fear have destabilizing
      effect while large population of predators has a stabilizing effect on the
      predator-prey interactions. Numerical simulations also imply that adult prey
      demonstrates stronger anti-predator behaviors if the population of predators is
      larger and shows weaker anti-predator behaviors if the cost of fear is larger.

PMID- 28508297
TI  - Adaptation to Stochastic Temporal Variations in Intratumoral Blood Flow: The
      Warburg Effect as a Bet Hedging Strategy.
AB  - While most cancers promote ingrowth of host blood vessels, the resulting vascular
      network usually fails to develop a mature organization, resulting in abnormal
      vascular dynamics with stochastic variations that include slowing, cessation, and
      even reversal of flow. Thus, substantial spatial and temporal variations in
      oxygen concentration are commonly observed in most cancers. Cancer cells, like
      all living systems, are subject to Darwinian dynamics such that their survival
      and proliferation are dependent on developing optimal phenotypic adaptations to
      local environmental conditions. Here, we consider the environmental stresses
      placed on tumors subject to profound, frequent, but stochastic variations in
      oxygen concentration as a result of temporal variations in blood flow. While
      vascular fluctuations will undoubtedly affect local concentrations of a wide
      range of molecules including growth factors (e.g., estrogen), substrate (oxygen,
      glucose, etc.), and metabolites ([Formula: see text], we focus on the selection
      forces that result solely from stochastic fluctuations in oxygen concentration.
      The glucose metabolism of cancer cells has been investigated for decades
      following observations that malignant cells ferment glucose regardless of oxygen
      concentration, a condition termed the Warburg effect. In contrast, normal cells
      cease fermentation under aerobic conditions and this physiological response is
      termed the Pasteur effect. Fermentation is markedly inefficient compared to
      cellular respiration in terms of adenosine triphosphate (ATP) production,
      generating just 2 ATP/glucose, whereas respiration generates 38 ATP/glucose. This
      inefficiency requires cancer cells to increase glycolytic flux, which
      subsequently increases acid production and can significantly acidify local
      tissue. Hence, it initially appears that cancer cells adopt a disadvantageous
      metabolic phenotype. Indeed, this metabolic "hallmark" of cancer is termed
      "energy dysregulation." However, if cancers arise through an evolutionary
      optimization process, any common observed property must confer an adaptive
      advantage. In the present work, we investigate the hypothesis that aerobic
      glycolysis represents an adaptation to stochastic variations in oxygen
      concentration stemming from disordered intratumoral blood flow. Using
      mathematical models, we demonstrate that the Warburg effect evolves as a
      conservative metabolic bet hedging strategy in response to stochastic
      fluctuations of oxygen. Specifically, the Warburg effect sacrifices fitness in
      physoxia by diverting resources from the more efficient process of respiration,
      but preemptively adapts cells to hypoxia because fermentation produces ATP
      anaerobically. An environment with sufficiently stochastic fluctuations of oxygen
      will select for the bet hedging (Warburg) phenotype since it is modestly
      successful irrespective of oxygen concentration.

PMID- 28508298
TI  - Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell
      Lineages.
AB  - Design principles of biological networks have been studied extensively in the
      context of protein-protein interaction networks, metabolic networks, and
      regulatory (transcriptional) networks. Here we consider regulation networks that
      occur on larger scales, namely the cell-to-cell signaling networks that connect
      groups of cells in multicellular organisms. These are the feedback loops that
      orchestrate the complex dynamics of cell fate decisions and are necessary for the
      maintenance of homeostasis in stem cell lineages. We focus on "minimal" networks
      that are those that have the smallest possible numbers of controls. For such
      minimal networks, the number of controls must be equal to the number of
      compartments, and the reducibility/irreducibility of the network (whether or not
      it can be split into smaller independent sub-networks) is defined by a matrix
      comprised of the cell number increments induced by each of the controlled
      processes in each of the compartments. Using the formalism of digraphs, we show
      that in two-compartment lineages, reducible systems must contain two 1-cycles,
      and irreducible systems one 1-cycle and one 2-cycle; stability follows from the
      signs of the controls and does not require magnitude restrictions. In three
      compartment systems, irreducible digraphs have a tree structure or have one 3
      cycle and at least two more shorter cycles, at least one of which is a 1-cycle.
      With further work and proper biological validation, our results may serve as a
      first step toward an understanding of ways in which these networks become
      dysregulated in cancer.

PMID- 28508299
TI  - Intensity response function of the photopic negative response (PhNR): effect of
      age and test-retest reliability.
AB  - PURPOSE: To assess the effect of age and test-retest reliability of the intensity
      response function of the full-field photopic negative response (PhNR) in normal
      healthy human subjects. METHODS: Full-field electroretinograms (ERGs) were
      recorded from one eye of 45 subjects, and 39 of these subjects were tested on two
      separate days with a Diagnosys Espion System (Lowell, MA, USA). The visual
      stimuli consisted of brief (<5 ms) red flashes ranging from 0.00625 to 6.4 phot
      cd.s/m2, delivered on a constant 7 cd/m2 blue background. PhNR amplitudes were
      measured at its trough from baseline (BT) and from the preceding b-wave peak
      (PT), and b-wave amplitude was measured at its peak from the preceding a-wave
      trough or baseline if the a-wave was not present. The intensity response data of
      all three ERG measures were fitted with a generalized Naka-Rushton function to
      derive the saturated amplitude (V max), semisaturation constant (K) and slope (n)
      parameters. Effect of age on the fit parameters was assessed with linear
      regression, and test-retest reliability was assessed with the Wilcoxon signed
      rank test and Bland-Altman analysis. Holm's correction was applied to account for
      multiple comparisons. RESULTS: V max of BT was significantly smaller than that of
      PT and b-wave, and the V max of PT and b-wave was not significantly different
      from each other. The slope parameter n was smallest for BT and the largest for b
      wave and the difference between the slopes of all three measures were
      statistically significant. Small differences observed in the mean values of K for
      the different measures did not reach statistical significance. The Wilcoxon
      signed-rank test indicated no significant differences between the two test visits
      for any of the Naka-Rushton parameters for the three ERG measures, and the Bland
      Altman plots indicated that the mean difference between test and retest
      measurements of the different fit parameters was close to zero and within 6% of
      the average of the test and retest values of the respective parameters for all
      three ERG measurements, indicating minimal bias. While the coefficient of
      reliability (COR, defined as 1.96 times the standard deviation of the test and
      retest difference) of each fit parameter was more or less comparable across the
      three ERG measurements, the %COR (COR normalized to the mean test and retest
      measures) was generally larger for BT compared to both PT and b-wave for each fit
      parameter. The Naka-Rushton fit parameters did not show statistically significant
      changes with age for any of the ERG measures when corrections were applied for
      multiple comparisons. However, the V max of BT demonstrated a weak correlation
      with age prior to correction for multiple comparisons, and the effect of age on
      this parameter showed greater significance when the measure was expressed as a
      ratio of the V max of b-wave from the same subject. CONCLUSION: V max of the BT
      amplitude measure of PhNR at the best was weakly correlated with age. None of the
      other parameters of the Naka-Rushton fit to the intensity response data of either
      the PhNR or the b-wave showed any systematic changes with age. The test-retest
      reliability of the fit parameters for PhNR BT amplitude measurements appears to
      be lower than those of the PhNR PT and b-wave amplitude measurements.

PMID- 28508300
TI  - The Symbolic Nature of Trust in Heterosexual Adolescent Romantic Relationships.
AB  - Trust contributes to young people's capacity for sustaining current and future
      successful relationships. To date, research has yet to examine the meaning of
      trust in early dating relationships and reasons for its deterioration. The
      present study focused on video-recorded conversations about trust between 34
      heterosexual adolescent couples in dating relationships living in the U.S.
      Transcripts from these conversations were qualitatively analyzed using thematic
      analysis to identify adolescents' meanings of trust and reasons they provided for
      a lack of trust in their romantic partners. All 34 couples identified concerns
      specifically related to infidelity. Six major themes for not trusting romantic
      partners emerged. Results suggested that the lack of trust in romantic
      relationships might stem from several areas that are directly and indirectly
      related to the current relationship, including low self-esteem, the experience of
      betrayal in past romantic relationships, partners' extradyadic behaviors, and
      gossip among peers. Importantly, peers can play a defining role in influencing
      young people's perceptions of their romantic partners and developing or
      sustaining trust in their romantic relationships.

PMID- 28508301
TI  - Sublingual heterotopic large cyst in a newborn: anesthetic management.

PMID- 28508302
TI  - Handedness and Attention Deficit/Hyperactivity Disorder Symptoms in College
      Students.
AB  - The symptoms of adult Attention Deficit/Hyperactivity Disorder (ADHD) generally
      include impaired concentration; an insensitivity to social cues, being hard to
      get along with, and being internally restlessness. It is not surprising that
      these problems are likely to affect the performance of college students with
      ADHD. The study aims to examine whether ADHD symptoms are associated with
      handedness in college students in Taiwan. A total of 505 male and 645 female
      participants completed Annett's handedness questionnaire and the Traditional
      Chinese College ADHD Response Evaluation Student Response Inventory (C-CARE-SRI).
      Handedness was scored both categorically, mixed vs. not-mixed, and continuously,
      using the Hand Preference Index. The Inattention score was significantly higher
      for students who were mixed-handed than for those who were not, after social
      pressure against using the left hand to write had been adjusted for. However, the
      differences in Hyperactivity and Impulsivity scores were nonsignificant. In
      addition, the correlations between all three ADHD and Hand Preference Index
      factor-scores were nonsignificant. To sum up, mixed-handedness is associated with
      a higher Inattention score. The potential underlying mechanism relating to ADHD
      Inattention is discussed.

PMID- 28508303
TI  - The effect of anger expression style on cardiovascular responses to lateralized
      cognitive stressors.
AB  - To determine the effects of self-reported anger expression style on cerebrally
      lateralized physiological responses to neuropsychological stressors, changes in
      systolic blood pressure and heart rate were examined in response to a verbal
      fluency task and a figural fluency task among individuals reporting either "anger
      in" or "anger out" expression styles. Significant group by trial interaction
      effects was found for systolic blood pressure following administration of verbal
      fluency [F(1,54) = 5.86, p < 0.05] and nonverbal fluency stressors [F(1,54) =
      13.68, p < .001]. Similar interactions were seen for systolic heart rate
      following administration of verbal fluency [F(1,54) = 5.86, p < .005] and
      nonverbal fluency stressors [F(1,54) = 13.68, p < .001]. The corresponding
      results are discussed in terms of functional cerebral systems and potential
      implications for physiological models of anger. Given the association between
      anger and negative physical health outcomes, there is a clear need to better
      understand the physiological components of anger. The results of this experiment
      indicate that a repressive "anger in" expression style is associated with
      deregulation of the right frontal region. This same region has been shown to be
      intimately involved in cardiovascular recovery, glucose metabolism, and blood
      pressure regulation.

PMID- 28508304
TI  - Effects of Pesticide Mixtures on Zooplankton Assemblages in Aquatic Microcosms
      Simulating Rice Paddy Fields.
AB  - The individual and combined effects of pesticides (chlorpyrifos, triadimefon and
      butachlor) on the zooplankton assemblages of microcosms were investigated.
      Laboratory microcosms were constructed with water and sediment to simulate
      aquatic conditions in China's rice paddy fields. Results from principal response
      curves analysis showed that butachlor and triadimefon had no significant impact
      individually on the population level in zooplankton assemblages. The deleterious
      effects of pesticide mixtures on the zooplankton were mainly caused by
      chlorpyrifos. In fact, assemblage succession only occurred in the treatments
      containing chlorpyrifos. There was no synergy effect on the microcosm from
      combinations of pesticides on the assemblages. The zooplankton assemblages
      affected by chlorpyrifos did not recover at the termination of the experiment,
      i.e., after 56 days.

PMID- 28508306
TI  - Multicenter, Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate
      0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues
      in Normal-Tension Glaucoma.
AB  - INTRODUCTION: This study compared the efficacy and safety of adjunctive
      brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate
      0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal
      tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of
      intraocular pressure (IOP) reduction. METHODS: In this multicenter, randomized,
      investigator-masked, parallel-group, clinical study, adjunctive brimonidine or
      timolol was administered twice daily for 12 weeks in eyes with NTG that had been
      treated with PGA for at least 90 days and required additional treatment despite
      an IOP of 16 mmHg or less. IOP was measured on at least three visits before add
      on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive
      administration. Systolic/diastolic blood pressure, pulse rate, and adverse events
      (AEs) were recorded at each visit. RESULTS: A total of 152 individuals were
      enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups
      at each visit decreased significantly from baseline (P < 0.001). However, the
      difference in the change from baseline IOP at week 12 between the brimonidine (
      1.05 +/- 1.81 mmHg) and timolol (-1.41 +/- 1.40 mmHg) groups was 0.36 mmHg (95%
      confidence interval [CI] [-0.21, 0.92]), which exceeded the value of the non
      inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure
      decreased significantly in both groups at certain visits (P < 0.05), while
      baseline pulse rates decreased significantly in the timolol group (P < 0.001),
      with no significant differences in the brimonidine group. AE-related treatment
      discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the
      brimonidine and timolol groups, respectively. CONCLUSION: This study demonstrated
      an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine
      to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was
      not observed. Brimonidine was associated with no adverse effects on pulse rate.
      FUNDING: Senju Pharmaceutical Co., Ltd. TRIAL REGISTRATION: UMIN Clinical Trials
      Registry identifier, UMIN000014810.

PMID- 28508305
TI  - Recent advances in targeting DNA repair pathways for the treatment of ovarian
      cancer and their clinical relevance.
AB  - Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as
      one of the major molecular-targeted therapeutics for inhibiting DNA damage
      response. The PARP inhibitor, olaparib, has been clinically applied for treating
      certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and
      the United States. It was also designated on 24 March 2017 as an orphan drug in
      Japan for similar clinical indications. In this review, we discuss (i) the
      prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP
      inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and
      ovarian cancer patients, and (iv) non-BRCA genes that may be associated with
      homologous recombination deficiency.

PMID- 28508307
TI  - Duration of Antiviral Prophylaxis and Risk of Herpes Zoster among Patients
      Receiving Autologous Hematopoietic Stem Cell Transplants: A Retrospective,
      Observational Study.
AB  - INTRODUCTION: There are no real-world data on antiviral prophylaxis (AP) duration
      and risk of herpes zoster (HZ) given AP duration in patients receiving autologous
      hematopoietic stem cell transplants (auto-HSCT). The objectives of this study are
      to describe the duration of AP and to compare incidence of HZ by AP duration in
      auto-HSCT patients. METHODS: This is a retrospective, observational database
      (Marketscan(r)) study. This study included patients >=18 years old who had auto
      HSCT during 2009-2013, had chemotherapy within 60 days prior to auto-HSCT (latest
      chemotherapy date within the 60 days was the study enrollment date), and had
      continuous health plan enrollment for at least 365 days before and after the
      study enrollment date. AP duration was the sum of days supply of all AP
      prescriptions from 30 days before to 365 days after the study enrollment date.
      Patients were followed from the study enrollment date to the end of continuous
      health plan enrollment, death, or December 31, 2014 to assess HZ incidence. The
      Cox proportional hazards model was used to examine the association between the
      risk of HZ and AP duration. RESULTS: This study identified 1959 eligible auto
      HSCT patients, of whom 93.0% were prescribed AP. Average AP duration was 220 days
      (SD = 122), while 200 (11%) patients had AP for >=1 year. HZ incidence was
      42.4/1000 person-years (PY) (95% CI 36.5, 49.0) for the overall auto-HSCT cohort.
      Among patients who received AP, duration of AP prescriptions and HZ incidence
      were inversely related. Compared with patients who were on AP for 1-89 days,
      patients with AP duration of 180-269 days [hazard ratio (HR) = 0.576, p = 0.019],
      270-359 days (HR = 0.594, p = 0.023), and >=360 days (HR = 0.309, p < 0.001) had
      significantly lower risk of HZ. CONCLUSION: Auto-HSCT patients are at increased
      risk for HZ, even when prescribed AP. A safe and effective vaccine against HZ for
      auto-HSCT patients could be a useful adjunctive prevention strategy.

PMID- 28508308
TI  - TRP Channel Classification.
AB  - The transient receptor potential (TRP) ion channels are named after the discovery
      of the photo-transducted channels in Drosophila. TRPs, activated by various
      extracellular and intracellular stimuli, play a plethora of physiological and
      pathological roles. There are seven families of TRPs including TRPC (canonical),
      TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), TRPML
      (mucolipin), and TRPN (Drosophila NOMPC) in mammals. In yeast, the eighth TRP
      family was recently identified and named as TRPY. We here briefly summarize the
      classification and function of TRP cation channel superfamily.

PMID- 28508309
TI  - TRPC Channel Structure and Properties.
AB  - TRPC channels are the first identified members in the TRP family. They function
      as either homo- or heterotetramers regulating intracellular Ca2+ concentration in
      response to numerous physiological or pathological stimuli. TRPC channels are
      nonselective cation channels permeable to Ca2+. The properties and the functional
      domains of TRPC channels have been identified by electrophysiological and
      biochemical methods. However, due to the large size, instability, and flexibility
      of their complexes, the structures of the members in TRPC family remain
      unrevealed. More efforts should be made on structure analysis and generating good
      tools, including specific antibodies, agonist, and antagonist.

PMID- 28508310
TI  - TRPC Channel Downstream Signaling Cascades.
AB  - The family of TRP channel is comprised of a large group of cation-permeable
      channels, displaying as signaling integrators for sensing extracellular stimulus
      and initiating intracellular signaling cascades. This chapter offers a brief
      review of the signaling molecules related to TRPC channels, the first identified
      mammalian TRP family. Besides the signaling molecules involved in TRPC
      activation, I will focus on their upstream and downstream signaling cascades and
      the molecules involved in their intracellular trafficking.

PMID- 28508311
TI  - TRPC Channels in Health and Disease.
AB  - This chapter offers a brief introduction of the functions of TRPC channels in non
      neuronal systems. We focus on three major organs of which the research on TRPC
      channels have been most focused on: kidney, heart, and lung. The chapter
      highlights on cellular functions and signaling pathways mediated by TRPC
      channels. It also summarizes several inherited diseases in humans that are
      related to or caused by TRPC channel mutations and malfunction. A better
      understanding of TRPC channels functions and the importance of TRPC channels in
      health and disease should lead to new insights and discovery of new therapeutic
      approaches for intractable disease.

PMID- 28508312
TI  - TRPC Channels and Programmed Cell Death.
AB  - Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic
      factor (BDNF), bind to their high-affinity receptors to promote neuronal survival
      during brain development. One of the key downstream pathways is the phospholipase
      C (PLC) pathway, which not only plays a central role in calcium release from
      internal store but also in activation of TRPC channels coupled with neurotrophin
      receptors. TRPC channels are required for the neurotrophin-mediated neuronal
      protective effects. In addition, activation of TRPC channels is able to protect
      neurons in the absence of neurotrophin. In some circumstances, TRPC channels
      coupled with metabotropic glutamate receptor may mediate the excitotoxicity by
      calcium overload. One of the key questions in the field is the channel gating
      mechanisms; understanding of which would help design compounds to modulate the
      channel properties. The development and identification of TRPC channel agonists
      or blockers are promising and may unveil new therapeutic drugs for the treatment
      of neurodegenerative diseases and epilepsy.

PMID- 28508313
TI  - TRPC Channels and Stroke.
AB  - TRPC channels play important roles in neuronal death/survival in ischemic stroke,
      vasospasm in hemorrhagic stroke, thrombin-induced astrocyte pathological changes,
      and also in the initiation of stroke by affecting blood pressure and
      atherogenesis. TRPCs' unique channel characters and downstream pathways make them
      possible new targets for stroke therapy. TRPC proteins have different functions
      in different cell types. Considering TRPCs' extensive distribution in various
      tissues and cell types, drugs targeting them could induce more complicated
      effects. More specific agonists/antagonists and antibodies are required for
      future study of TRPCs as potential targets for stroke therapy.

PMID- 28508314
TI  - TRPC Channels and Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease in the
      world. The "amyloid hypothesis" is one of the predominant hypotheses for the
      pathogenesis of AD. Besides, tau protein accumulation, calcium homeostasis
      disruption, and glial cell activation are also remarkable features in AD.
      Recently, there are some reports showing that TRPC channels may function in AD
      development, especially TRPC6. In this chapter, we will discuss the evidence for
      the involvement of TRPC channels in Alzheimer's disease and the potential of
      therapeutics for AD based on TRPC channels.

PMID- 28508316
TI  - TRPC Channels and Neuron Development, Plasticity, and Activities.
AB  - In this chapter, we mainly focus on the functions of TRPC channels in brain
      development, including neural progenitor proliferation, neurogenesis, neuron
      survival, axon guidance, dendritic morphology, synaptogenesis, and neural
      plasticity. We also notice emerging advances in understanding the functions of
      TRPC channels in periphery, especially their functions in sensation and
      nociception in dorsal root ganglion (DRG). Because TRPC channels are expressed in
      all major types of glial cells, which account for at least half of total cells in
      the brain, TRPC channels may act as modulators for glial functions as well. The
      future challenges for studying these channels could be (1) the detailed protein
      structures of these channels, (2) their cell type-specific functions, (3)
      requirement for their specific blockers or activators, and (4) change in the
      channel conformation in the brain.

PMID- 28508318
TI  - TRPC Channels and Epilepsy.
AB  - Accumulating evidence suggest that TRPC channels play critical roles in various
      aspects of epileptogenesis. TRPC1/4 channels are major contributors to
      nonsynaptically derived epileptiform burst firing in the CA1 and the lateral
      septum. TRPC7 channels play a critical role in synaptically derived epileptiform
      burst firing. The reduction of spontaneous epileptiform bursting in the CA3 is
      correlated to a reduction in pilocarpine-induced SE in vivo in TRPC7 knockout
      mice. TRPC channels are also significant contributors to SE-induced neuronal cell
      death. Although the pilocarpine-induced SE itself is not significantly reduced,
      the SE-induced neuronal cell death is significantly reduced in the CA1 and the
      lateral septum, indicating that TRPC1/4 channels directly contribute to SE
      induced neuronal cell death. Genetic ablation of TRPC5 also reduces SE-induced
      neuronal cell death in the CA1 and CA3 areas of the hippocampus.

PMID- 28508317
TI  - TRPC Channels and Brain Inflammation.
AB  - Nonresolving low-grade inflammation is supposed to underly the basis of chronic
      disorders including cardiovascular diseases, cancer, diabetes, obesity, and
      psychiatric disorders such as depression and Alzheimer's diseases. There is
      increasing evidence suggesting that pathophysiology of psychiatric disorders is
      related to the inflammatory responses mediated by microglial cells. Elevation of
      intracellular Ca2+ is important for the activation of microglial cell functions,
      including proliferation, release of NO, cytokines, and BDNF. It has been shown
      that alteration of intracellular Ca2+ signaling underlies the pathophysiology of
      psychiatric disorders, including depression. BDNF induces a sustained
      intracellular Ca2+ elevation through the upregulation of the surface expression
      of TRPC3 channels in rodent microglial cells. Microglial cells are able to
      respond to BDNF, which may be important for the regulation of inflammatory
      responses and may also be involved in the pathophysiology and/or the treatment of
      psychiatric disorders. We also need to study the effect of proBDNF on microglial
      cells especially by focusing on the TRPC channels.

PMID- 28508319
TI  - TRPC Channels and Mental Disorders.
AB  - Transient receptor potential canonical (TRPC) channels mediate the influx of
      different types of cations through the cell membrane and are involved in many
      functions of the organism. Evidences of involvement of TRPC channels in neuronal
      development suggest that this family of proteins might play a role in certain
      neurological disorders. As reported, knockout mice for different TRPC channels
      show alterations in neuronal morphological and functional parameters, with
      behavioral abnormalities, such as in exploratory and social behaviors. Although
      mutations in TRPC channels could be related to mental/neurological disorders,
      there are only a few cases reported in literature, indicating that this
      correlation should be further explored. Nonetheless, other functional evidences
      support the implication of these channels in neurological diseases. In this
      chapter, we summarize the main findings relating TRPC channels to neurological
      disorders, such as autism spectrum disorders, bipolar disorder, and intellectual
      disability among others.

PMID- 28508315
TI  - TRPC Channels and Parkinson's Disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder, which involves
      degeneration of dopaminergic neurons that are present in the substantia nigra
      pars compacta (SNpc) region. Many factors have been identified that could lead to
      Parkinson's disease; however, almost all of them are directly or indirectly
      dependent on Ca2+ signaling. Importantly, though disturbances in Ca2+ homeostasis
      have been implicated in Parkinson's disease and other neuronal diseases, the
      identity of the calcium channel remains elusive. Members of the transient
      receptor potential canonical (TRPC) channel family have been identified as a new
      class of Ca2+ channels, and it could be anticipated that these channels could
      play important roles in neurodegenerative diseases, especially in PD. Thus, in
      this chapter we have entirely focused on TRPC channels and elucidated its role in
      PD.

PMID- 28508320
TI  - TRPC Channels and Cell Proliferation.
AB  - TRPCs have been demonstrated to be widely expressed in different cancers. In
      recent years, a number of studies closely investigated the roles of TRPCs in
      cancer cells. Most of the results show that both mRNA and protein levels of TRPCs
      significantly increase in cancer tissues compared with healthy controls. TRPCs
      regulate Ca2+ homeostasis, contribute to cell cycle regulation and the
      expression/activation of Ca2+-related factors, and thus play critical roles in
      the proliferation of cancer cells. Therefore, TRPCs could act as potential drug
      targets for cancer diagnosis and therapy.

PMID- 28508321
TI  - TRPC Channels and Glioma.
AB  - Glioma is the most common type of brain tumors and malignant glioma is extremely
      lethal, with patients' 5-year survival rate less than 10%. Treatment of gliomas
      poses remarkable clinical challenges, not only because of their particular
      localization but also because glioma cells possess several malignant biological
      features, including highly proliferative, highly invasive, highly angiogenic, and
      highly metabolic aberrant. All these features make gliomas highly recurrent and
      drug resistant. Finding new and effective molecular drug targets for glioma is an
      urgent and critical task for both basic and clinical research. Recent studies
      have proposed a type of non-voltage-gated calcium channels, namely, canonical
      transient receptor potential (TRPC) channels, to be newly emerged potential drug
      targets for glioma. They are heavily involved in the proliferation, migration,
      invasion, angiogenesis, and metabolism of glioma cells. Abundant evidence from
      both cell models and preclinical mouse models has demonstrated that inhibition of
      TRPC channels shows promising anti-glioma effect. In this chapter, we will give a
      comprehensive review on the current progress in the studies on TRPC channels and
      glioma and discuss their potential clinical implication in glioma therapy.

PMID- 28508322
TI  - Use patterns of first-line inhibitors of tyrosine kinase and time to change to
      second-line therapy in chronic myeloid leukemia.
AB  - Background Chronic myeloid leukemia (CML) has a low incidence but a high burden
      of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI).
      Objective To determine the time from the start of a first-line TKI until it
      passes to second-line, and to establish the reasons for the change of therapy
      time. Setting Patients with Philadelphia-positive CML treated with some TKI.
      Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with
      information obtained from medical records, the time to change initial drugs to
      secondline therapy, and the reasons for change, were identified. Kaplan-Meier
      survival analysis was carried out. Main outcome measure A change in therapy to
      the secondline TKI and the final reason for the change of therapy. Results A
      total of 247 patients treated were found in 22 cities in Colombia with a mean age
      of 53.2 +/- 15.2 years. The drug most used as initial therapy was imatinib; 53.8%
      of cases had to change to another TKI. 50% of patients changed therapy in 42
      months, men in 24 and women in 67 months (95% CI 14.314-33.686; p = 0.001). Being
      male (OR 2.23; 95% CI 1.291-3.854; p = 0.004) and receiving hydroxyurea (OR 3.65;
      95% CI 1.601-8.326; p = 0.002) were associated with a higher probability of
      switching to nilotinib or dasatinib, while receiving a new-generation TKI (OR
      0.15; 95% CI 0.071-0.341; p < 0.001) reduced this risk. Conclusions A high
      proportion of patients needed to change to a second line with nilotinib and
      dasatinib management. It is necessary to obtain more real world evidence, to
      improve the effectiveness, adherence and safety of the treatment.

PMID- 28508323
TI  - The impact of pharmacy monitoring and intervention in patients receiving
      intravenous heparin.
AB  - Background Intravenous unfractionated heparin (IV UFH) has a narrow therapeutic
      index and poses a high risk of bleeding. Objective To determine the impact of
      pharmacy monitoring and intervention on adherence to and appropriate
      implementation of IV UFH protocol. Setting A 438 bed hospital specializing in
      cardiac services. Methods This is a retrospective chart review study. Pre
      pharmacy intervention data were collected from November 2013 to January 2014 and
      compared to post-pharmacy intervention data obtained between August 2014 and
      October 2014. Patients were included if they received IV UFH for at least 24
      hours. The first three daytime laboratory draws were collected for each patient
      and analyzed using generalized estimating equations to quantify the association
      between pharmacy monitoring and adherence to the institution's protocol. Main
      outcome measures Designation of appropriate protocol, accurate selection of
      initial infusion rate, timing of anti-Xa levels within 60 min of anticipated due
      time, change of infusion rate within 120 min of laboratory result, and
      appropriate adjustment of infusion rates. Results A total of 195 data points were
      included. The initial selection of infusion rate and subsequent adjustments were
      more appropriate in the post-intervention period with an odds ratio of 8.36 (95%
      CI 2.41-29.01, p value = 0.0008), and 4.66 (95% CI 1.41-15.43, p value = 0.0118),
      respectively. Conclusion The results of this study indicate that pharmacy
      monitoring of IV UFH therapy has improved adherence to an institution's protocol
      and is associated with more accurate selection of initial infusion rates and
      adjustment of infusions based upon laboratory results.

PMID- 28508324
TI  - Impact of clinical pharmacist intervention in anticoagulation clinic in Sudan.
AB  - Background Many trials have compared anticoagulation management provided by a
      pharmacist led anticoagulation clinic versus usual physician care showing the
      role for clinical pharmacist in the management of anticoagulant therapy, and
      demonstrating excellent outcomes. In Sudan, there is no published research
      evaluating the role of pharmacist in providing pharmaceutical care for patients
      taking warfarin. Objective The objective of the study is to assess the role of
      clinical pharmacist intervention in warfarin patients compared to usual medical
      care. Setting This study was conducted in Ahmed Gasim cardiac surgery and renal
      transplant center warfarin clinic. Methods One hundred thirty-five patients were
      randomly selected from adult patients on warfarin therapy The history of INR
      records, and adverse effects for the past year, were recorded. Then patients'
      warfarin dose adjustments according to INR, was done by the clinical pharmacist
      for one year. Patients received continuous verbal education and written
      information about warfarin. Main outcome measure The primary outcome for this
      study was the INR control, while the secondary outcomes were the bleeding events
      and hospitalization due to warfarin. Results After the clinical pharmacist
      intervention there was significant (P < 0.01) improvement in INR control and a
      significant (P < 0.05) reduction in incidence of bleeding after clinical
      pharmacist intervention. Hospitalization due to warfarin related complications
      (bleeding, high INR, low INR) was also significantly (P < 0.001) reduced.
      Conclusion Clinical pharmacists intervention in warfarin therapy improve INR
      control, reduce bleeding and hospitalization due to warfarin complications.

PMID- 28508325
TI  - Preliminary Results of a Novel Algorithmic Method Aiming to Support Initial
      Causality Assessment of Routine Pharmacovigilance Case Reports for Medication
      Induced Liver Injury: The PV-RUCAM.
AB  - INTRODUCTION: Data incompleteness in pharmacovigilance (PV) health records limits
      the use of current causality assessment methods for drug-induced liver injury
      (DILI). In addition to the inherent complexity of this adverse event, identifying
      cases of high causal probability is difficult. OBJECTIVE: The aim was to evaluate
      the performance of an improved, algorithmic and standardised method called the
      Pharmacovigilance-Roussel Uclaf Causality Assessment Method (PV-RUCAM), to
      support assessment of suspected DILI. Performance was compared in different
      settings with regard to applicability and differentiation capacity. METHODS: A PV
      RUCAM score was developed based on the seven sections contained in the original
      RUCAM. The score provides cut-off values for or against DILI causality, and was
      applied on two datasets of bona fide individual case safety reports (ICSRs)
      extracted randomly from clinical trial reports and a third dataset of electronic
      health records from a global PV database. The performance of PV-RUCAM
      adjudication was compared against two standards: a validated causality assessment
      method (original RUCAM) and global introspection. RESULTS: The findings showed
      moderate agreement against standards. The overall error margin of no false
      negatives was satisfactory, with 100% sensitivity, 91% specificity, a 25%
      positive predictive value and a 100% negative predictive value. The Spearman's
      rank correlation coefficient illustrated a statistically significant monotonic
      association between expert adjudication and PV-RUCAM outputs (R = 0.93). Finally,
      there was high inter-rater agreement (K w = 0.79) between two PV-RUCAM assessors.
      CONCLUSION: Within the PV setting of a pharmaceutical company, the PV-RUCAM has
      the potential to facilitate and improve the assessment done by non-expert PV
      professionals compared with other methods when incomplete reports must be
      evaluated for suspected DILI. Prospective validation of the algorithmic tool is
      necessary prior to implementation for routine use.

PMID- 28508326
TI  - The association of low penetrance genetic risk modifiers with colorectal cancer
      in lynch syndrome patients: a systematic review and meta-analysis.
AB  - Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition
      syndrome accounting for approximately 1000 cases of colorectal cancer (CRC) in
      the UK annually. LS is characterised by autosomal dominant inheritance and
      germline mutations in DNA mismatch repair genes. The penetrance is highly
      variable and the reasons for this have not been fully elucidated. This study
      investigates whether low penetrance genetic risk factors may result in phenotype
      modification in LS patients. To conduct a systematic literature review and meta
      analysis to assess the association between low penetrance genetic risk modifiers
      and CRC in LS patients. A systematic review was conducted of the PubMed and
      HuGENet databases. Eligibility of studies was determined by pre-defined criteria.
      Included studies were analysed via the per-allele model and assessed by pooled
      odds ratios and establishing 95% confidence intervals. Study heterogeneity was
      assessed via Cochrane's Q statistic and I2 values. Publication bias was evaluated
      with funnel plots. Subgroup analysis was conducted on gender. Statistical
      software used was the Metafor package for the R programme version 3.1.3. Sixty
      four polymorphisms were identified and sufficient data was available for analysis
      of ten polymorphisms, with between 279 and 1768 CRC cases per polymorphism. None
      demonstrated association with CRC risk in LS patients. However in sub-group
      analysis the polymorphism rs16892766 (8q23.3) was significant in males (OR 1.53,
      95% CI 1.12-2.10). The variable phenotype presentation of the disease still
      remains largely unexplained, and further investigation is warranted. Other
      factors may also be influencing the high variability of the disease, such as
      environmental factors, copy number variants and epigenetic alterations.
      Investigation into these areas is needed as well as larger and more definitive
      studies of the polymorphisms analysed in this study.

PMID- 28508327
TI  - Assessment of molecular markers demonstrates concordance between samples acquired
      via stereotactic biopsy and open craniotomy in both anaplastic astrocytomas and
      glioblastomas.
AB  - The classification, treatment and prognosis of high-grade gliomas has been shown
      to correlate with the expression of molecular markers (e.g. MGMT promotor
      methylation and IDH1 mutations). Acquisition of tumor samples may be obtained via
      stereotactic biopsy or open craniotomy. Between the years 2009 and 2013, 22
      patients initially diagnosed with HGGs via stereotactic biopsy, that ultimately
      underwent open craniotomy for resection of their tumor were prospectively
      included in an institutional glioma database. MGMT promotor analysis was
      performed using methylation-specific (MS)-PCR and IDH1R132H mutation analysis was
      performed using immunohistochemistry. Three patients (13.7%) exhibited IDH1R132H
      mutations in samples obtained via stereotactic biopsy. Tissue derived from
      stereotaxic biopsy was demonstrated to have MGMT promotor methylation in ten
      patients (45.5%), while a non-methylated MGMT promotor was demonstrated in ten
      patients (45.5%); inconclusive results were obtained for the remaining two
      patients (9%) within our cohort. The initial histologic grading, IDH1R132H
      mutation and MGMT promotor methylation results were confirmed using samples
      obtained during open craniotomy in all but one patient; here inconclusive MGMT
      promotor analysis was obtained in contrast to that which was obtained via
      stereotactic biopsy. Tumor samples acquired via stereotactic biopsy provide
      accurate information with regard to clinically relevant molecular markers that
      have been shown to impact patient care decisions. The profile of markers analyzed
      in our cohort was nearly concordant between those samples obtained via
      stereotactic biopsy or open craniotomy thereby suggesting that clinical decisions
      may be based on the molecular profile of the tumor samples obtained via
      stereotactic biopsy.

PMID- 28508328
TI  - MiR-424 functions as a tumor suppressor in glioma cells and is down-regulated by
      DNA methylation.
AB  - Glioma is one of the most lethal malignancies, and increasing reports revealed
      that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role
      in the development and pathology of human gliomas. MiR-424 has been found to be
      dysregulated in many different types of human cancers. However, the clinical
      significance and function of miR-424 in glioma remains unclear. Here, based on
      RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was
      significantly decreased in glioma tumor tissues than in adjacent non-neoplastic
      brain tissues, and decreased miR-424 expression was associated with glioma KPS (P
      = 0.009) and high grades (P = 0.029). In vitro cellular function assays further
      revealed that miR-424 inhibited cell invasion and migration, and promoted cell
      apoptosis. In addition, based on DNA methylation analysis on clinical specimens
      and cell lines, we found miR-424 promoter CpG island was frequently methylated
      and correlated with glioma high grades (P = 0.035) and IDH mutation status (P =
      0.042). Moreover, the promoter CpG island was demethylated by 5-aza-2'
      deoxycytidine treatment in a time-dependent manner and the expression levels of
      miR-424 were gradually induced and increased. Taken together, our data suggest
      that the promoter region CpG island methylation is associated with tumor
      suppressive miR-424 silencing and the pathology of human gliomas.

PMID- 28508329
TI  - Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma.
AB  - Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer
      than 200 nucleotides. Their critical roles in different biological pathways have
      been already well established. Altered expression of lncRNAs can be involved in
      the cancer initiation and/or progression. Since patients with hepatocellular
      carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic
      methods seems to be essential. In this study, the expression levels of different
      lncRNAs were systematically analysed in different genomic and transcriptome
      datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive
      dysregulation of expression and copy number variation in HCC tumors compared with
      normal tissues. The results also suggest that the dysregulation of SNHG6 is
      highly cancer type specific. Through co-occurrence analyses, we found that SNHG6
      and its related co-expressed genes on 8q are involved in the structural integrity
      of ribosome and translation. This comprehensive in silico analysis, provides a
      resource for investigating SNHG6 in hepatocellular carcinoma and lays the
      groundwork for design of next researches.

PMID- 28508330
TI  - Mediators of Weight Loss Maintenance in the Keep It Off Trial.
AB  - Background: An important step toward enhancing the efficacy of weight loss
      maintenance interventions is identifying the pathways through which successful
      interventions such as the Keep It Off trial have worked. Purpose: This study
      aimed to assess the viability of mediated relationships between the Keep It Off
      Guided intervention, conceptually and empirically grounded potential mediators,
      and weight. Repeated measurement of mediators and weight enabled documentation of
      the temporal ordering of intervention delivery and changes in mediators and in
      weight among participants randomized to the Guided intervention or Self-Directed
      comparison group. Methods: Total, direct, and indirect effects of the Guided
      intervention on weight change were calculated and tested for significance.
      Indirect effects were comprised of the influence of the intervention on three
      change scores for each mediator and the relationship between mediator changes and
      weight changes 6 months later. Results: Guided intervention participants regained
      about 2% less weight over 24 months than Self-Directed participants. Starting
      daily self-weighing accounted for the largest share of this difference, followed
      by not stopping self-weighing. Conclusions: Daily self-weighing mediated 24-month
      weight loss maintenance. Trial Registration Number: The trial is registered with
      ClinicalTrials.gov (Identifier: NCT00702455
      www.clinicaltrials.gov/ct2/show/NCT00702455).

PMID- 28508331
TI  - Is pesticide sorption by constructed wetland sediments governed by water level
      and water dynamics?
AB  - Constructed wetlands (CWs) are used to reduce the pesticide inputs from tile
      drainage or run-off to surface water. Their effectiveness appears variable and
      remains to be better characterized and understood. The aim of this study was to
      assess the influences of two hydraulic parameters (i.e., dynamics and water
      level) on the sorption process occurring in CWs. Then, two solid/liquid ratios
      were studied (1/1 and 1/5) to mimic the water level variation in the field, and
      two agitation speeds were used (none and gentle agitation) to simulate different
      water dynamics (stagnation and flow pass, respectively). Sorption kinetics and
      isotherms were obtained for four pesticides with contrasting properties. The
      pesticide adsorption coefficients were classified as follows: boscalid (BSC) >
      cyproconazole (CYP) > isoproturon (IPU) ~ dimethachlor (DMT) at any ratio or
      agitation, in agreement with their water solubilities and K ow values. The effect
      of the solid/liquid ratio was evidenced for all conditions. Indeed, the
      adsorption equilibrium time was reached more quickly for the 1/1 ratio (24-72 h)
      than for the 1/5 ratio (96-120 h). In addition, the adsorption coefficients (K
      fads) were larger for the 1/1 ratio (1.8-11.2 L kg-1) than for the 1/5 ratio (1.0
      5.9 L kg-1). The agitation effect was  more evidenced for the 1/5 ratio and for
      the more hydrophobic molecules, such as BSC and CYP, for which adsorption
      equilibrium time was never reached with agitation (>120 h), while it was reached
      at 96 h without agitation. Moreover, the K fads values were larger with agitation
      than without agitation for BSC and CYP, whereas they were similar for the two
      agitations for IPU and DMT. Our results demonstrated that the hydrodynamic
      function of CWs could influence pesticide sorption with variable effects
      according to the molecular properties and consequently influence the mitigation
      effect of CWs throughout the year.

PMID- 28508332
TI  - Occurrence of diazepam and its metabolites in wastewater and surface waters in
      Beijing.
AB  - Occurrence of diazepam and its metabolites, nordiazepam, temazepam, and oxazepam
      in the water environment in Beijing was investigated. Samples were collected from
      four rivers flowing through the city and from all the thirteen sewage treatment
      plants in the urban area. Average influent concentrations of diazepman,
      temazepam, and oxazepam in 2013 summer ranged from 0.9 to 7.1, 1.5 to 3.4, and
      2.9 to 12.4 ng L-1, respectively, whereas nordiazepam concentrations were below
      quantification limit on the majority of sampling dates. No significant seasonal
      variation in influent concentrations was observed. Removal during treatment was
      low for diazepman (<50%), temazepam (<20%), and oxazepam (<20%), consistent with
      previous findings reported in the literature. Wastewater-based epidemiology
      approach was applied to back-calculate population size-normalized diazepam
      consumption (using temazepam as biomarker) in Beijing, which was found to be at
      least 3.8 times more of the national average. Diazepam, temazepam, and oxazepam
      were widely detected in surface waters, with concentrations greater than
      concentrations in sewage influents at many sampling points, strongly indicating
      direct discharge of wastewater of high diazepam concentrations into the surface
      waters in the city.

PMID- 28508333
TI  - Levels and risk assessment of metals in sediment and fish from Chaohu Lake, Anhui
      Province, China.
AB  - Chaohu Lake is the fifth largest freshwater lake in China, which tolerates
      substantial amount of anthropogenic discharge from surrounding cities that
      resulting in the degradation of water and damage of aquatic ecosystem. Metal
      analysis of sediment and aquatic organisms can provide important information on
      the environmental contamination and potential impact of aquatic food consumption.
      Thus, the concentrations of Cu, Pb, Zn, Cr, Cd, As, and Hg in sediment and fish
      from Chaohu Lake were analyzed with inductively coupled plasma mass spectrometry
      and atomic fluorescence spectrometry. The mean content of Cu, Pb, Zn, Cr, Cd, As,
      and Hg in the sediment samples were 27.4 +/- 6.3, 40.5 +/- 12.3, 136.8 +/- 65.5,
      68.5 +/- 9.1, 0.357 +/- 0.141, 10.8 +/- 1.7, and 0.117 +/- 0.049 mg/kg,
      respectively. The results were compared with background values and evaluation
      methods, to characterize the potential ecological risk. The concentrations of Cu,
      Pb, Zn, Cr, Cd, As, and Hg in the fish muscle samples were 1.68-5.31, 0.078-0.31,
      15.55-372.98, 0.31-0.93, 0.001-0.033, 0.29-1.03, and 0.04-0.197 mg kg-1 of dry
      mass, respectively. Most of the concentrations of the studied metals in muscles
      were found to be below the safe limits; however, the concentration of inorganic
      As (10% of total As) in two specimens exceeded the maximum allowance in fish. The
      ecological risk evaluation showed that the metals in sediment posed low to medium
      risk. The health risk assessment suggested that the consumption of fish from
      Chaohu Lake is currently safe with respect to the metals.

PMID- 28508334
TI  - A survey of mycotoxin contamination and chemical composition of distiller's dried
      grains with solubles (DDGS) imported from the USA into Saudi Arabia.
AB  - Distiller's dried grains with solubles (DDGS) is a source of nutritional
      feedstuff for poultry farmers and industry. The DDGS is a by-product of ethanol
      industry and an economical feed source of energy, amino acids, crude fiber,
      minerals, and vitamins. The use of DDGS as a feed ingredient is a novel idea and
      little information is available on its dietary composition. Many factors such as
      the type of plants, locality, year of production, and the conditions during
      distillation process affect the chemical composition of DDGS. In this paper, the
      chemical composition and the presence of mycotoxin in DDGS imported from the USA
      into Saudi Arabia as a feedstuff for poultry have been documented.

PMID- 28508335
TI  - Toxic potential of organic constituents of submicron particulate matter (PM1) in
      an urban road site (Barcelona).
AB  - Atmospheric particulate matter (PM) is a recognized risk factor contributing to a
      number of diseases in human populations and wildlife globally. Organic matter is
      a major component of PM, but its contribution to overall toxicity of PM has not
      been thoroughly evaluated yet. In the present work, the biological activity of
      organic extracts from PM1 (particles with less than 1 MUm of aerodynamic
      diameter) collected from an urban road site in the centre of Barcelona (NE Spain)
      was evaluated using a yeast-based assay (AhR-RYA) and different gene expression
      markers in zebrafish embryos. Dioxin-like activity of the extracts correlated to
      primary emissions from local traffic exhausts, reflecting weekday/weekend
      alternance. Expression levels of cyp1a and of gene markers for key cellular
      processes and development (ier2, fos) also correlated to vehicle emissions,
      whereas expression of gene markers related to antioxidant defence and endocrine
      effects (gstal, hao1, ttr) was strongly reduced in samples with strong
      contribution from regional air masses with aged secondary organic species or with
      strong influence of biomass burning emissions. Our data suggest that the toxic
      potential of PM1 organic chemical constituents strongly depends on the emission
      sources and on the process of ageing from primary to secondary organic aerosols.

PMID- 28508336
TI  - The impacts of non-renewable and renewable energy on CO2 emissions in Turkey.
AB  - As a result of great increases in CO2 emissions in the last few decades, many
      papers have examined the relationship between renewable energy and CO2 emissions
      in the energy economics literature, because as a clean energy source, renewable
      energy can reduce CO2 emissions and solve environmental problems stemming from
      increases in CO2 emissions. When one analyses these papers, he/she will observe
      that they employ fixed parameter estimation methods, and time-varying effects of
      non-renewable and renewable energy consumption/production on greenhouse gas
      emissions are ignored. In order to fulfil this gap in the literature, this paper
      examines the effects of non-renewable and renewable energy on CO2 emissions in
      Turkey over the period 1970-2013 by employing fixed parameter and time-varying
      parameter estimation methods. Estimation methods reveal that CO2 emissions are
      positively related to non-renewable energy and renewable energy in Turkey. Since
      policy makers expect renewable energy to decrease CO2 emissions, this paper
      argues that renewable energy is not able to satisfy the expectations of policy
      makers though fewer CO2 emissions arise through production of electricity using
      renewable sources. In conclusion, the paper argues that policy makers should
      implement long-term energy policies in Turkey.

PMID- 28508337
TI  - Natural radionuclide dose and lifetime cancer risk due to ingestion of fish and
      water from fresh water reservoirs near the proposed uranium mining site.
AB  - Ten sampling locations in Nagarjuna Sagar Dam have been selected to assess the
      suitability of the reservoir water for human consumption. The sediment, water,
      and fish samples were collected and analyzed for radionuclide (238U, 232Th,
      210Po, 226Ra, 210Pb) and physicochemical parameters like pH, TOC, total hardness,
      alkalinity, DO, cation exchange capacity, and particle size. The spatial
      variations among the radionuclides (238U, 232Th, 210Po, 226Ra, 210Pb) in water
      and bottom sediments of Nagarjuna Sagar Dam were determined. The uranium
      concentration in the sediment and water was in BDL (<0.5 ppb). The maximum
      permissible limits in water samples of the analyzed radionuclides are 238U-10
      Bq/l, 210Po-0.1 Bq/l, 226Ra-1 Bq/l, and 210Pb-0.1 Bq/l. The radionuclides in our
      water samples were approximately 50 times far below the recommended limit. The
      ingestion of water and fish would not pose any significant radiological impact on
      health or cancer risk to the public, implicating that the fishes from Nagarjuna
      Sagar Dam reservoir are safe for human consumption except the fisherman
      community.

PMID- 28508339
TI  - Induction of hibernation-like hypothermia by central activation of the A1
      adenosine receptor in a non-hibernator, the rat.
AB  - Central adenosine A1-receptor (A1AR)-mediated signals play a role in the
      induction of hibernation. We determined whether activation of the central A1AR
      enables rats to maintain normal sinus rhythm even after their body temperature
      has decreased to less than 20  degrees C. Intracerebroventricular injection of an
      adenosine A1 agonist, N6-cyclohexyladenosine (CHA), followed by cooling decreased
      the body temperature of rats to less than 20  degrees C. Normal sinus rhythm was
      fundamentally maintained during the extreme hypothermia. In contrast, forced
      induction of hypothermia by cooling anesthetized rats caused cardiac arrest.
      Additional administration of pentobarbital to rats in which hypothermia was
      induced by CHA also caused cardiac arrest, suggesting that the operation of some
      beneficial mechanisms that are not activated under anesthesia may be essential to
      keep heart beat under the hypothermia. These results suggest that central A1AR
      mediated signals in the absence of anesthetics would provide an appropriate
      condition for maintaining normal sinus rhythm during extreme hypothermia.

PMID- 28508338
TI  - Fluid Balance in Team Sport Athletes and the Effect of Hypohydration on
      Cognitive, Technical, and Physical Performance.
AB  - Sweat losses in team sports can be significant due to repeated bursts of high
      intensity activity, as well as the large body size of athletes, equipment and
      uniform requirements, and environmental heat stress often present during training
      and competition. In this paper we aimed to: (1) describe sweat losses and fluid
      balance changes reported in team sport athletes, (2) review the literature
      assessing the impact of hypohydration on cognitive, technical, and physical
      performance in sports-specific studies, (3) briefly review the potential
      mechanisms by which hypohydration may impact team sport performance, and (4)
      discuss considerations for future directions. Significant hypohydration (mean
      body mass loss (BML) >2%) has been reported most consistently in soccer. Although
      American Football, rugby, basketball, tennis, and ice hockey have reported high
      sweating rates, fluid balance disturbances have generally been mild (mean BML
      <2%), suggesting that drinking opportunities were sufficient for most athletes to
      offset significant fluid losses. The effect of hydration status on team sport
      performance has been studied mostly in soccer, basketball, cricket, and baseball,
      with mixed results. Hypohydration typically impaired performance at higher levels
      of BML (3-4%) and when the method of dehydration involved heat stress. Increased
      subjective ratings of fatigue and perceived exertion consistently accompanied
      hypohydration and could explain, in part, the performance impairments reported in
      some studies. More research is needed to develop valid, reliable, and sensitive
      sport-specific protocols and should be used in future studies to determine the
      effects of hypohydration and modifying factors (e.g., age, sex, athlete caliber)
      on team sport performance.

PMID- 28508342
TI  - Current strategies in the diagnosis of endometrial cancer.
AB  - PURPOSE: Endometrial cancer is the most common gynecological malignancy in
      developed countries. There are no uniform recommendations for endometrial cancer
      screening in the general population. Therefore, it is of paramount importance
      that the primary physician profoundly understands, and is familiar with the
      methods for prevention and early detection of endometrial cancer. The aim of this
      review is to provide the primary physician with a toolbox to reach these goals.
      METHODS: We performed a systemic review to summarize the current strategies to
      diagnose and prevent endometrial cancer. Many published articles from the last
      years were identified and included. RESULTS: A systematic review that summarizes
      the important subjects in the diagnosis and prevention of endometrial cancer.
      CONCLUSION: Maintaining a high index of suspicion and obtaining endometrial
      biopsies from all suspected patients is the key for achieving a timely diagnosis.

PMID- 28508340
TI  - Comparative effects of sertraline, haloperidol or olanzapine treatments on
      ketamine-induced changes in mouse behaviours.
AB  - Effects of sertraline, haloperidol or olanzapine administration on ketamine
      induced behaviours in mice were examined. The aim was to ascertain the degree of
      reversal of such behaviours by sertraline, and compare its effectiveness to
      haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into
      main groups; 1 (open-field, radial-arm maze and elevated plus maze {EPM} tests),
      and 2 (social interaction test). Mice in each main group were assigned into six
      groups of ten (n = 10) each. Group 1 received intraperitoneal (i.p) injection of
      vehicle, while groups 2-6 received i.p ketamine at 15 mg/kg daily for 10 days.
      From day 11 to 24, mice in group 1 (vehicle) were given distilled water (i.p at 2
      ml/kg and oral at 10 ml/kg), group 2 (ketamine control) received daily i.p
      ketamine and oral distilled water; while animals in groups 3-6 received daily
      i.p. ketamine and oral haloperidol (4 mg/kg), olanzapine (2 mg/kg), or one of two
      doses of sertraline (SERT) (2.5 or 5 mg/kg), respectively. Treatments were
      administered daily, and behaviours assessed on days 11 and 24. Results showed
      that repeated ketamine administration caused hyperlocomotion, increased self
      grooming, memory loss and social withdrawal. Administration of sertraline (both
      doses), haloperidol, and olanzapine reversed ketamine-induced behavioural
      changes. However, in the EPM, sertraline and olanzapine were anxiolytic, while
      haloperidol was anxiogenic. Sertraline's effect on behaviours tested was
      comparable to olanzapine and better than haloperidol. In conclusion, this study
      shows that sertraline's ability to counteract ketamine-induced behavioural
      changes in mice is comparable to known antipsychotics.

PMID- 28508343
TI  - Cytomegalovirus infection in pregnancy.
AB  - PURPOSE: Due to the severe risk of long-term sequelae, prenatal cytomegalovirus
      infection is of particular importance amongst intrauterine viral infections. This
      review summarizes the current knowledge about CMV infection in pregnancy.
      METHODS: A search of the Medline and Embase database was done for articles about
      CMV infection in pregnany. We performed a detailed review of the literature in
      view of diagnosis, epidemiology and management of CMV infection in pregnancy.
      RESULTS: The maternal course of the infection is predominantly asymptomatic; the
      infection often remains unrecognized until the actual fetal manifestation.
      Typical ultrasound signs that should arouse suspicion of intrauterine CMV
      infection can be distinguished into CNS signs such as ventriculomegaly or
      microcephaly and extracerebral infection signs such as hepatosplenomegaly or
      hyperechogenic bowel. Current treatment strategies focus on hygienic measures to
      prevent a maternal CMV infection during pregnancy, on maternal application of
      hyperimmunoglobulines to avoid materno-fetal transmission in case of a maternal
      seroconversion, and on an antiviral therapy in case the materno-fetal
      transmission have occurred. CONCLUSION: CMV infection in pregnancy may result in
      a severe developmental disorder of the newborn. This should be taken into account
      in the treatment of affected and non-affected pregnant women.

PMID- 28508341
TI  - Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.
AB  - Huntington disease (HD) is an inherited neurodegenerative disorder caused by
      mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in,
      and especially influence of the level of mitochondrial DNA (mtDNA) on,
      development of this disease is unclear. Here, samples of blood from 84 HD
      patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9
      controls were analysed for mtDNA levels. Although the type of mitochondrial
      haplogroup had no influence on the mtDNA level, and there was no correlation
      between mtDNA level in leukocytes in HD patients and various parameters of HD
      severity, some considerable differences between HD patients and controls were
      identified. The average mtDNA/nDNA relative copy number was significantly higher
      in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to
      the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes
      than HD men. Because this is the largest population analysed to date, these
      results might contribute to explanation of discrepancies between previously
      published studies concerning levels of mtDNA in cells of HD patients. We suggest
      that the size of the investigated population and type of cells from which DNA is
      isolated could significantly affect results of mtDNA copy number estimation in
      HD. Hence, these parameters should be taken into consideration in studies on
      mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction
      occurs.

PMID- 28508344
TI  - Vaginal hysterectomy versus laparoscopically assisted vaginal hysterectomy for
      large uteri between 280 and 700 g: a randomized controlled trial.
AB  - OBJECTIVE: To compare surgical outcomes, postoperative complications and costs
      between vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy
      in cases of large uteri. METHODS: Prospective randomized controlled trial done at
      Ain Shams University Maternity Hospital, where 50 patients were recruited and
      divided into two equal groups (each 25 patients). First group underwent vaginal
      hysterectomy, and the second underwent laparoscopically assisted vaginal
      hysterectomy. RESULTS: Patient characteristics were similar in both groups. As
      for surgical outcomes, estimated intraoperative blood loss (P = 0.90), operative
      time (P = 0.48), preoperative hemoglobin (P = 0.09), postoperative hemoglobin (P
      = 0.42), and operative complications (P = 1.0) did not differ between the two
      groups. The hospital costs (converted from Egyptian pound to U.S. dollars) were
      significantly higher in case of LAVH group [VH: $1060.86 ($180.09) versus LAVH:
      $1560.5 ($220.57), P value <0.001]. No significant difference exists in the
      duration of postoperative hospital stay between the two groups [VH: 49.92 h
      (28.50) versus LAVH: 58.56 (27.78), P = 0.28] or the actual uterine weight
      measured postoperatively [VH: 350.72 g (71.78) versus LAVH: 385.96 g (172.52), P
      = 0.35]. CONCLUSION: Both vaginal hysterectomy and laparoscopically assisted
      vaginal hysterectomy are safe procedures in cases of large uteri with no
      significant difference between them except in terms of costs as VH appears to be
      more cost effective. CLINICAL TRIALS.GOV: NCT02826304.

PMID- 28508345
TI  - Deep monocular 3D reconstruction for assisted navigation in bronchoscopy.
AB  - PURPOSE: In bronchoschopy, computer vision systems for navigation assistance are
      an attractive low-cost solution to guide the endoscopist to target peripheral
      lesions for biopsy and histological analysis. We propose a decoupled deep
      learning architecture that projects input frames onto the domain of CT
      renderings, thus allowing offline training from patient-specific CT data.
      METHODS: A fully convolutional network architecture is implemented on GPU and
      tested on a phantom dataset involving 32 video sequences and [Formula: see
      text]60k frames with aligned ground truth and renderings, which is made available
      as the first public dataset for bronchoscopy navigation. RESULTS: An average
      estimated depth accuracy of 1.5 mm was obtained, outperforming conventional
      direct depth estimation from input frames by 60%, and with a computational time
      of [Formula: see text]30 ms on modern GPUs. Qualitatively, the estimated depth
      and renderings closely resemble the ground truth. CONCLUSIONS: The proposed
      method shows a novel architecture to perform real-time monocular depth estimation
      without losing patient specificity in bronchoscopy. Future work will include
      integration within SLAM systems and collection of in vivo datasets.

PMID- 28508347
TI  - Does Helicobacter pylori infection increase the risk of adult-onset asthma?

PMID- 28508346
TI  - Testosterone insulin-like effects: an in vitro study on the short-term metabolic
      effects of testosterone in human skeletal muscle cells.
AB  - PURPOSE: Testosterone by promoting different metabolic pathways contributes to
      short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue
      and the primary site for insulin-stimulated glucose utilization. Despite
      evidences indicate a close relationship between testosterone and glucose
      metabolism, the molecular mechanisms responsible for a possible testosterone
      mediated insulin-like effects on skeletal muscle are still unknown. METHODS: Here
      we used undifferentiated proliferating or differentiated human fetal skeletal
      muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the
      insulin-mediated biomolecular metabolic machinery. GLUT4 cell expression,
      localization and the phosphorylation/activation of AKT, ERK, mTOR and GSK3beta
      insulin-related pathways at different time points after treatment with
      testosterone were analyzed. RESULTS: Independently from cells differentiation
      status, testosterone, with an insulin-like effect, induced Glut4-mRNA expression,
      GLUT4 protein translocation to the cytoplasmic membrane, while no effect was
      observed on GLUT4 protein expression levels. Furthermore, testosterone treatment
      modulated the insulin-dependent signal transduction pathways inducing a rapid and
      persistent activation of AKT, ERK and mTOR, and a transient inhibition of
      GSK3beta. T-related effects were shown to be androgen receptor dependent.
      CONCLUSION: All together our data indicate that testosterone through the
      activation of non-genomic pathways, participates in skeletal muscle glucose
      metabolism by inducing insulin-related effects.

PMID- 28508348
TI  - Cost analysis of minimally invasive radical hysterectomy for cervical cancer
      performed by a single surgeon in an Italian center: an update in gynecologic
      oncological field.
AB  - The objective of this study is to perform an economic analysis and examine the
      influence of procedural volume of our hospital, evaluating the accounting systems
      of Robotic radical hysterectomy (RRH) vs Laparoscopic radical hysterectomy (TLRH)
      in patients with cervical carcinoma, due to the costs widely variable and lack in
      literature. Costs were collected prospectively, from March 2010 to March 2016.
      Direct costs were determined by examining the overall medical pathway for each
      type of intervention. 52 patients with cervical carcinoma, which were matched by
      age, body mass index, tumor size, International Federation of Gynecology and
      Obstetrics (FIGO) stage, comorbidity, previous neoadjuvant chemotherapy,
      histology type, and tumor grade to obtain homogeneous samples. Surgical time was
      similar for both the groups. RRH was associated with a significantly less (EBL)
      estimated blood loss (P = 0.000). The overall median length of follow-up was of
      59 months. The cost of the robot-specific supplies was ?2705 per intervention.
      When considering overall medical surgical care, the patient treatment average
      cost of an RRH was ?5650,31 with an hospital stay (HS) of 3.58 days (SD +/- 1) vs
      ?3750.86 for TRLH, with an HS of 4.27 days (SD +/- 1.79). Our results are similar
      to Finnish data; the costs of robot-assisted hysterectomies were 1.5 times higher
      than TLRH. The main drivers of additional costs are robotic disposable
      instruments, which are not compensated by the hospital room costs and by an
      experienced team staff. Implementation of strategies to reduce the cost of
      robotic instrumentation is due. RRH resulted less expensive than robotic simple
      hysterectomy for benign conditions.

PMID- 28508349
TI  - The Contemporary Role of Stents and Angioplasty for the Treatment of
      Infrapopliteal Disease in Critical Limb Ischemia.
AB  - PURPOSE OF REVIEW: Critical limb ischemia (CLI) is associated with significant
      morbidity, mortality, and increased health care expenses. Revascularization has a
      central role in the treatment of CLI. Following publication of BASIL (bypass
      versus angioplasty in severe ischemia of the leg) trial a decade ago, an
      "endovascular first" approach had gained momentum and the technologies available
      for endovascular therapy have exponentially increased. Both the development of
      technology and technique, highlighted in this review, have allowed operators to
      treat complex infrapopliteal lesions which are central to CLI pathology. RECENT
      FINDINGS: The role of atherectomy remains controversial but for calcified lesions
      it has become an accepted adjunctive tool for plaque modification. The place of
      drug delivery technologies requires further trials. The use of a drug-coated
      balloon (DCB) makes intuitive sense; however, choice of excipient, lower limit of
      vessel size, and impact on remodeling and thrombosis remain uncertain. The
      optimal treatment of infrapopliteal disease remains an area of active
      investigation. The endpoints in CLI trials continue to be challenging and
      calibration of patency in relation to wound healing remains a moving target. In
      addition, unaccounted variables continue to confound interpretation of CLI trials
      including quality and nature of wound care, status of pedal-plantar loop patency,
      and management of underlying diabetes and other comorbidities. In summary, these
      challenges will also need to be addressed as the CLI field continues to mature in
      the twenty-first century.

PMID- 28508350
TI  - Targeted Nuclear Imaging Probes for Cardiac Amyloidosis.
AB  - PURPOSE OF REVIEW: The aim of the present manuscript is to review the latest
      advancements of radionuclide molecular imaging in the diagnosis and prognosis of
      individuals with cardiac amyloidosis. RECENT FINDINGS: 99mTechnetium labeled bone
      tracer scintigraphy had been known to image cardiac amyloidosis, since the 1980s;
      over the past decade, bone scintigraphy has been revived specifically to diagnose
      transthyretin cardiac amyloidosis. 18F labeled and 11C labeled amyloid binding
      radiotracers developed for imaging Alzheimer's disease, have been repurposed
      since 2013, to image light chain and transthyretin cardiac amyloidosis.
      99mTechnetium bone scintigraphy for transthyretin cardiac amyloidosis, and
      amyloid binding targeted PET imaging for light chain and transthyretin cardiac
      amyloidosis, are emerging as highly accurate methods. Targeted radionuclide
      imaging may soon replace endomyocardial biopsy in the evaluation of patients with
      suspected cardiac amyloidosis. Further research is warranted on the role of
      targeted imaging to quantify cardiac amyloidosis and to guide therapy.

PMID- 28508351
TI  - Native and Non-native Speakers' Brain Responses to Filled Indirect Object Gaps.
AB  - We examined native and non-native English speakers' processing of indirect object
      wh-dependencies using a filled-gap paradigm while recording event-related
      potentials (ERPs). The non-native group was comprised of native German-speaking,
      proficient non-native speakers of English. Both participant groups showed
      evidence of linking fronted indirect objects to the subcategorizing verb when
      this was encountered, reflected in an N400 component. Evidence for continued
      filler activation beyond the verb was seen only in the non-native group, in the
      shape of a prolonged left-anterior negativity. Both participant groups showed
      sensitivity to filled indirect object gaps reflected in a P600 response, which
      was more pronounced and more globally distributed in our non-native group. Taken
      together, our results indicate that resolving indirect object dependencies is a
      two-step process in both native and non-native sentence comprehension, with
      greater processing cost incurred in non-native compared to native comprehension.

PMID- 28508353
TI  - What matters when judging intentionality-moral content or normative status?
      Testing the rational scientist model of the side-effect.
AB  - Previous work has demonstrated a "side-effect effect," such that intentionality
      is more likely to be attributed to agents who bring about negatively valenced as
      opposed to positively valenced side effects. The rational-scientist model
      explains this by suggesting that norm-violating side effects are more informative
      for inferring intentionality than norm-conforming side effects. In the present
      study we reexamined this account, addressing limitations of previous empirical
      tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence
      and norm status were manipulated factorially, enabling an examination of the
      impact of norm status on intentionality judgments in both positively and
      negatively valenced side effects. Additionally, the impact of side-effect norm
      status on the perceived valences of side effects and agents was examined. Effects
      of norm status were found for both positive and negative side effects. Violation
      of an ostensibly neutral norm led to negative perceptions of the side effect.
      However, a norm status effect on intentionality judgments persisted when these
      effects were controlled. These results support the view that the side-effect
      effect is the result of the rational use of social-cognitive evidence.

PMID- 28508352
TI  - Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the
      missing link in the infectious etiology theory?
AB  - Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood
      malignancy, arises from an expansion of malignant B cell precursors in the bone
      marrow. Epidemiological studies suggest that infections or immune responses to
      infections may promote such an expansion and thus BCP-ALL development.
      Nevertheless, a specific pathogen responsible for this process has not been
      identified. BCP-ALL cells critically depend on interactions with the bone marrow
      microenvironment. The bone marrow is also home to memory T helper (Th) cells that
      have previously expanded during an immune response in the periphery. In secondary
      lymphoid organs, Th cells can interact with malignant cells of mature B cell
      origin, while such interactions between Th cells and malignant immature B cell in
      the bone marrow have not been described yet. Nevertheless, literature supports a
      model where Th cells-expanded during an infection in early childhood-migrate to
      the bone marrow and support BCP-ALL cells as they support normal B cells. Further
      research is required to mechanistically confirm this model and to elucidate the
      interaction pathways between leukemia cells and cells of the tumor
      microenvironment. As benefit, targeting these interactions could be included in
      current treatment regimens to increase therapeutic efficiency and to reduce
      relapses.

PMID- 28508354
TI  - Patient and Public Preferences for Treatment Attributes in Parkinson's Disease.
AB  - BACKGROUND: Patient and public preferences for therapeutic outcomes or medical
      technologies are often elicited, and discordance between the two is frequently
      reported. OBJECTIVE: Our main objective was to compare patient and public
      preferences for treatment attributes in Parkinson's disease (PD). METHODS: A
      representative sample from Dutch PD patients and the general public were invited
      to complete a best-worst scaling case 2 experiment consisting of six health
      related outcomes and one attribute describing the specific treatment (brain
      surgery, pump, oral medication). Data were analyzed using mixed logit models, and
      attribute impact was estimated and compared between populations (and population
      subgroups). RESULTS: Both the public (N = 276) and patient (N = 198) populations
      considered treatment modality the most important attribute, although patients
      assigned higher relative importance. Both groups assigned high disutility to pump
      infusion and brain surgery and preferred drug treatment. Most health outcomes
      were valued equally by patients and the public, with the exception of reducing
      dizziness (more important to the public) and improving slow movement (more
      important to patients). DISCUSSION: Although these data do not support definite
      conclusions on whether patients are less likely to undergo invasive treatments,
      the (predicted) choice probability of undergoing brain surgery or having pump
      infusion technology would be low based on the (un)desirability of the attribute
      levels. Patients with PD might have adapted to their condition and are not
      willing to undergo advanced treatments in order to receive health improvements.
      Both public and patient preferences entail information that is potentially
      relevant for decision makers, and patient preferences can inform decision makers
      about the likelihood of adaptation to a specific condition.

PMID- 28508355
TI  - Neuroproteomics Studies: Challenges and Updates.
AB  - The Human Genome Project in 2003 has resulted in the complete sequence of ~99% of
      the human genome paving the road for the Human Proteome Project (HPP) assessing
      the full characterization of the translated protein map of the 20,300 protein
      coding genes. Consequently, the emerging of the proteomics field has successfully
      been adopted as the method of choice for the proteome characterization.
      Proteomics is a term that is used to encompass multidisciplinary approaches
      combining different technologies that aim to study the entire spectrum of protein
      changes at a specific physiological condition. Proteomics research has shown
      excellent outcomes in different fields, among which is neuroscience; however, the
      complexity of the nervous systems necessitated the genesis of a new subdiscipline
      of proteomics termed as "neuroproteomics." Neuroproteomics studies involve
      assessing the quantitative and qualitative aspects of nervous system components
      encompassing global dynamic events underlying various brain-related disorders
      ranging from neuropsychiatric disorders, degenerative disorders, mental illness,
      and most importantly brain-specific neurotrauma-related injuries. In this
      introductory chapter, we will provide a brief historical perspective on the field
      of neuroproteomics. In doing so, we will highlight on the recent applications of
      neuroproteomics in the areas of neurotrauma, an area that has benefitted from
      neuroproteomics in terms of biomarker research, spatiotemporal injury mechanism,
      and its use to translate its findings from experimental settings to human
      translational applications. Importantly, this chapter will include some
      recommendation to the general studies in the area of neuroproteomics and the need
      to move from this field from being a descriptive, hypothesis-free approach to
      being an independent mature scientific discipline.

PMID- 28508357
TI  - Biofluid Proteomics and Biomarkers in Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is an injury to the brain caused by an external
      mechanical force, affecting millions of people worldwide. The disease course and
      prognosis are often unpredictable, and it can be challenging to determine an
      early diagnosis in case of mild injury as well as to accurately phenotype the
      injury. There is currently no cure for TBI-drugs having failed repeatedly in
      clinical trials-but an intense effort has been put to identify effective
      neuroprotective treatment. The detection of novel biomarkers, to understand more
      of the disease mechanism, facilitates early diagnosis, predicts disease
      progression, and develops molecularly targeted therapies that would be of high
      clinical interest. Over the last decade, there has been an increasing effort and
      initiative toward finding TBI-specific biomarker candidates. One promising
      strategy has been to use state-of-the-art neuroproteomics approaches to assess
      clinical biofluids and compare the cerebrospinal fluid (CSF) and blood proteome
      between TBI and control patients or between different subgroups of TBI. In this
      chapter, we summarize and discuss the status of biofluid proteomics in TBI, with
      a particular focus on the latest findings.

PMID- 28508356
TI  - Progress and Potential of Imaging Mass Spectrometry Applied to Biomarker
      Discovery.
AB  - Mapping provides a direct means to assess the impact of protein biomarkers and
      puts into context their relevance in the type of cancer being examined. To this
      end, mass spectrometry imaging (MSI) was developed to provide the needed spatial
      information which is missing in traditional liquid-based mass spectrometric
      proteomics approaches. Aptly described as a "molecular histology" technique, MSI
      gives an additional dimension in characterizing tumor biopsies, allowing for
      mapping of hundreds of molecules in a single analysis. A decade of developments
      focused on improving and standardizing MSI so that the technique can be
      translated into the clinical setting. This review describes the progress made in
      addressing the technological development that allows to bridge local protein
      detection by MSI to its identification and to illustrate its potential in
      studying various aspects of cancer biomarker discovery.

PMID- 28508358
TI  - Degradomics in Neurotrauma: Profiling Traumatic Brain Injury.
AB  - Degradomics has recently emerged as a subdiscipline in the omics era with a focus
      on characterizing signature breakdown products implicated in various disease
      processes. Driven by promising experimental findings in cancer, neuroscience, and
      metabolomic disorders, degradomics has significantly promoted the notion of
      disease-specific "degradome." A degradome arises from the activation of several
      proteases that target specific substrates and generate signature protein
      fragments. Several proteases such as calpains, caspases, cathepsins, and matrix
      metalloproteinases (MMPs) are involved in the pathogenesis of numerous diseases
      that disturb the physiologic balance between protein synthesis and protein
      degradation. While regulated proteolytic activities are needed for development,
      growth, and regeneration, uncontrolled proteolysis initiated under pathological
      conditions ultimately culminates into apoptotic and necrotic processes. In this
      chapter, we aim to review the protease-substrate repertoires in neural injury
      concentrating on traumatic brain injury. A striking diversity of protease
      substrates, essential for neuronal and brain structural and functional integrity,
      namely, encryptic biomarker neoproteins, have been characterized in brain injury.
      These include cytoskeletal proteins, transcription factors, cell cycle regulatory
      proteins, synaptic proteins, and cell junction proteins. As these substrates are
      subject to proteolytic fragmentation, they are ceaselessly exposed to activated
      proteases. Characterization of these molecules allows for a surge of "possible"
      therapeutic approaches of intervention at various levels of the proteolytic
      cascade.

PMID- 28508359
TI  - Evolving Relevance of Neuroproteomics in Alzheimer's Disease.
AB  - Substantial progress in the understanding of the biology of Alzheimer's disease
      (AD) has been achieved over the past decades. The early detection and diagnosis
      of AD and other age-related neurodegenerative diseases, however, remain a
      challenging scientific frontier. Therefore, the comprehensive discovery (relating
      to all individual, converging or diverging biochemical disease mechanisms),
      development, validation, and qualification of standardized biological markers
      with diagnostic and prognostic functions with a precise performance profile
      regarding specificity, sensitivity, and positive and negative predictive value
      are warranted.Methodological innovations in the area of exploratory high
      throughput technologies, such as sequencing, microarrays, and mass spectrometry
      based analyses of proteins/peptides, have led to the generation of large global
      molecular datasets from a multiplicity of biological systems, such as biological
      fluids, cells, tissues, and organs. Such methodological progress has shifted the
      attention to the execution of hypothesis-independent comprehensive exploratory
      analyses (opposed to the classical hypothesis-driven candidate approach), with
      the aim of fully understanding the biological systems in physiology and disease
      as a whole. The systems biology paradigm integrates experimental biology with
      accurate and rigorous computational modelling to describe and foresee the dynamic
      features of biological systems. The use of dynamically evolving technological
      platforms, including mass spectrometry, in the area of proteomics has enabled to
      rush the process of biomarker discovery and validation for refining significantly
      the diagnosis of AD. Currently, proteomics-which is part of the systems biology
      paradigm-is designated as one of the dominant matured sciences needed for the
      effective exploratory discovery of prospective biomarker candidates expected to
      play an effective role in aiding the early detection, diagnosis, prognosis, and
      therapy development in AD.

PMID- 28508360
TI  - Genome to Phenome: A Systems Biology Approach to PTSD Using an Animal Model.
AB  - Post-traumatic stress disorder (PTSD) is a debilitating illness that imposes
      significant emotional and financial burdens on military families. The
      understanding of PTSD etiology remains elusive; nonetheless, it is clear that
      PTSD is manifested by a cluster of symptoms including hyperarousal,
      reexperiencing of traumatic events, and avoidance of trauma reminders. With these
      characteristics in mind, several rodent models have been developed eliciting PTSD
      like features. Animal models with social dimensions are of particular interest,
      since the social context plays a major role in the development and manifestation
      of PTSD.For civilians, a core trauma that elicits PTSD might be characterized by
      a singular life-threatening event such as a car accident. In contrast, among war
      veterans, PTSD might be triggered by repeated threats and a cumulative
      psychological burden that coalesced in the combat zone. In capturing this
      fundamental difference, the aggressor-exposed social stress (Agg-E SS) model
      imposes highly threatening conspecific trauma on naive mice repeatedly and
      randomly.There is abundant evidence that suggests the potential role of genetic
      contributions to risk factors for PTSD. Specific observations include putatively
      heritable attributes of the disorder, the cited cases of atypical brain
      morphology, and the observed neuroendocrine shifts away from normative. Taken
      together, these features underscore the importance of multi-omics investigations
      to develop a comprehensive picture. More daunting will be the task of downstream
      analysis with integration of these heterogeneous genotypic and phenotypic data
      types to deliver putative clinical biomarkers. Researchers are advocating for a
      systems biology approach, which has demonstrated an increasingly robust potential
      for integrating multidisciplinary data. By applying a systems biology approach
      here, we have connected the tissue-specific molecular perturbations to the
      behaviors displayed by mice subjected to Agg-E SS. A molecular pattern that links
      the atypical fear plasticity to energy deficiency was thereby identified to be
      causally associated with many behavioral shifts and transformations.PTSD is a
      multifactorial illness sensitive to environmental influence. Accordingly, it is
      essential to employ the optimal animal model approximating the environmental
      condition that elicits PTSD-like symptoms. Integration of an optimal animal model
      with a systems biology approach can contribute to a more knowledge-driven and
      efficient next-generation care management system and, potentially, prevention of
      PTSD.

PMID- 28508361
TI  - Photoaffinity Labeling of Pentameric Ligand-Gated Ion Channels: A Proteomic
      Approach to Identify Allosteric Modulator Binding Sites.
AB  - Photoaffinity labeling techniques have been used for decades to identify drug
      binding sites and to study the structural biology of allosteric transitions in
      transmembrane proteins including pentameric ligand-gated ion channels (pLGIC). In
      a typical photoaffinity labeling experiment, to identify drug binding sites, UV
      light is used to introduce a covalent bond between a photoreactive ligand (which
      upon irradiation at the appropriate wavelength converts to a reactive
      intermediate) and amino acid residues that lie within its binding site. Then
      protein chemistry and peptide microsequencing techniques are used to identify
      these amino acids within the protein primary sequence. These amino acid residues
      are located within homology models of the receptor to identify the binding site
      of the photoreactive probe. Molecular modeling techniques are then used to model
      the binding of the photoreactive probe within the binding site using docking
      protocols. Photoaffinity labeling directly identifies amino acids that contribute
      to drug binding sites regardless of their location within the protein structure
      and distinguishes them from amino acids that are only involved in the
      transduction of the conformational changes mediated by the drug, but may not be
      part of its binding site (such as those identified by mutational studies). Major
      limitations of photoaffinity labeling include the availability of photoreactive
      ligands that faithfully mimic the properties of the parent molecule and protein
      preparations that supply large enough quantities suitable for photoaffinity
      labeling experiments. When the ligand of interest is not intrinsically
      photoreactive, chemical modifications to add a photoreactive group to the parent
      drug, and pharmacological evaluation of these chemical modifications become
      necessary. With few exceptions, expression and affinity-purification of proteins
      are required prior to photolabeling. Methods to isolate milligram quantities of
      highly enriched pLGIC suitable for photoaffinity labeling experiments have been
      developed. In this chapter, we discuss practical aspects of experimental
      strategies to identify allosteric modulator binding sites in pLGIC using
      photoaffinity labeling.

PMID- 28508362
TI  - Quantitative Phosphoproteomic Analysis of Brain Tissues.
AB  - Protein phosphorylation regulates brain development and neuronal activities; and
      dysregulation of phosphorylation contributes to neurobiological disorders.
      Phosphoproteomic analysis provides comprehensive modification maps for measuring
      protein activities in cellular pathways and biological processes. Here, we
      introduce a mass spectrometry (MS)-based protocol to quantitatively analyze the
      phosphoproteome of human postmortem brains of Alzheimer's disease. In this
      isobaric labeling protocol, up to ten brain samples are selected from control and
      diseased cases for comparison. Approximately 1 mg proteins per sample are
      extracted, digested, labeled, and then mixed at an equal ratio. To improve the
      coverage of phosphoproteome, the peptide mix is further fractionated by offline
      basic pH reversed-phase liquid chromatography (LC) with high-resolution power.
      Phosphopeptides in each fraction are then enriched by the titanium dioxide method
      and analyzed by online acidic pH reverse phase LC-MS/MS, leading to the analysis
      of tens of thousands of phosphorylation events. This protocol can also be adapted
      to profile phosphoproteome in other biological samples.

PMID- 28508364
TI  - A Novel 2-DE-Based Proteomic Analysis to Identify Multiple Substrates for
      Specific Protease in Neuronal Cells.
AB  - Proteolysis is a process where proteins are broken down into smaller polypeptides
      or amino acids, comprising one of the important posttranslational modifications
      of proteins. Since this process is exquisitely achieved by specialized enzymes
      called proteases under physiological conditions, abnormal protease activity and
      dysregulation of their substrate proteins are closely associated with a
      progression of several neurodegenerative diseases including Alzheimer disease,
      Parkinson disease, stroke, and spinal cord injury. Thus, it is important to
      identify the specific substrates of proteases with nonbiased high-throughput
      screenings to understand how proteolysis contributes to neurodegeneration. Here,
      we described a so-called gel-based protease proteomic approach. Critical steps of
      our novel strategy consist of two-dimensional polyacrylamide gel electrophoresis
      (2-DE)-based protein separation and in vitro incubation with the specific
      protease of interest. As a prototypic example, cellular lysates obtained from
      neuronal cells are separated by an isoelectric focusing, and the resulting
      immobilized proteins on a gel strip are incubated with a predetermined amount of
      a recombinant or a purified protease. By densitometric analysis of the Coomassie
      Brilliant Blue-stained gel images following separation by 2-DE, significantly
      altered protein spots are subjected to a mass spectral analysis for protein
      identification. Interestingly, the concepts of our strategy can be applied to any
      proteases, and to any neural cells or neural tissues of one's interest. Since the
      immobilized protein spots are exposed to the purified protease, this protocol
      ensures the identification of only substrates that are directly cleaved by
      specific protease. This protocol ensures to avoid the possibility of identifying
      substrates that may be cleaved by combinatorial or sequential activation of
      proteolytic enzymes present in a liquid state of the lysates. We propose that our
      strategy can be effectively utilized to provide meaningful insights into newly
      identified protease substrates and to decipher molecular mechanisms critically
      involved in neurodegenerative processes.

PMID- 28508363
TI  - Glycoproteins Enrichment and LC-MS/MS Glycoproteomics in Central Nervous System
      Applications.
AB  - Proteins and glycoproteins play important biological roles in central nervous
      systems (CNS). Qualitative and quantitative evaluation of proteins and
      glycoproteins expression in CNS is critical to reveal the inherent biomolecular
      mechanism of CNS diseases. This chapter describes proteomic and glycoproteomic
      approaches based on liquid chromatography/tandem mass spectrometry (LC-MS or LC
      MS/MS) for the qualitative and quantitative assessment of proteins and
      glycoproteins expressed in CNS. Proteins and glycoproteins, extracted by a mass
      spectrometry friendly surfactant from CNS samples, were subjected to enzymatic
      (tryptic) digestion and three down-stream analyses: (1) a nano LC system coupled
      with a high-resolution MS instrument to achieve qualitative proteomic profile,
      (2) a nano LC system combined with a triple quadrupole MS to quantify identified
      proteins, and (3) glycoprotein enrichment prior to LC-MS/MS analysis. Enrichment
      techniques can be applied to improve coverage of low abundant
      glycopeptides/glycoproteins. An example described in this chapter is hydrophilic
      interaction liquid chromatographic (HILIC) enrichment to capture glycopeptides,
      allowing efficient removal of peptides. The combination of three LC-MS/MS-based
      approaches is capable of the investigation of large-scale proteins and
      glycoproteins from CNS with an in-depth coverage, thus offering a full view of
      proteins and glycoproteins changes in CNS.

PMID- 28508365
TI  - Neuroproteomic Profiling of Cerebrospinal Fluid (CSF) by Multiplexed Affinity
      Arrays.
AB  - Protein profiling through affinity proteomic approaches represents a powerful
      strategy for the analysis of human body fluids. Cerebrospinal fluid (CSF), being
      the fluid proximal to the central nervous system, is commonly analyzed in the
      context of neurological diseases, and can offer novel insights into the
      physiological state of the brain. Ultimately, and by analyzing the presence of
      brain-derived proteins in larger sets of samples that represent different
      phenotypes, profiling of CSF may serve as an important source to discover and
      verify disease-associated markers. Here, we describe a multiplexed and flexible
      protein profiling approach using antibody-based assays on suspension bead arrays.
      Through streamlined sample processing, protein biotinylation, and single-binder
      assay readout, this method enables high-throughput neuroproteomic analysis of up
      to 384 proteins in 384 samples.

PMID- 28508366
TI  - Isolation and Proteomic Analysis of Microvesicles and Exosomes from HT22 Cells
      and Primary Neurons.
AB  - Exosomes and microvesicles are extracellular vesicles (EVs) released by most cell
      types. The role of EVs as a method of intercellular communication has led to
      these vesicles becoming a major area of interest in a variety of scientific
      fields including neuroscience. Emerging evidence is now demonstrating that the
      biomolecular composition of EVs, especially exosomes, can play a role in the
      progression of disease including various neurodegenerative diseases and cancer.
      In addition to the miRNA profiles of EVs, these vesicles also show interesting
      changes in protein expression profiles under different physiological and
      pathological conditions. Characterization of these profiles could prove valuable
      for both understanding disease pathogenesis and for the discovery of new
      biomarkers of disease. In this chapter, we describe a protocol for isolation of
      exosomes and microvesicles from immortalized HT22 cells and primary cortical
      neurons with sufficient yield and low serum contamination required for downstream
      analysis and label-free relative quantitation by mass spectrometry.

PMID- 28508367
TI  - Combined MALDI Mass Spectrometry Imaging and Parafilm-Assisted Microdissection
      Based LC-MS/MS Workflows in the Study of the Brain.
AB  - Proteins and other biomolecules such as lipids are significant players in the
      central nervous system and are implicated in various neurological disorders.
      Their identification, quantification, and distribution are thus important not
      only in understanding the disease but also in developing treatments. A combined
      workflow allowing the localized microextraction of discrete regions identified by
      a matrix-assisted laser desorption/ionization mass spectrometry (MSI) imaging
      experiment for proteomics analysis by liquid chromatography/tandem mass
      spectrometry (LC MS/MS) is described in this chapter. MSI was initially used to
      map lipid distributions allowing for the identification of regions of interest
      (ROIs) that are then subjected to microextraction in a consecutive tissue
      section. Mounting of consecutive tissue on parafilm allows microdissection of the
      ROIs, where proteins can then be recovered for processing and LC MS/MS analysis.
      The PAM method provides a fast and cheap means to perform further downstream
      analysis after an MSI experiment.

PMID- 28508368
TI  - De Novo and Uninterrupted SILAC Labeling of Primary Microglia.
AB  - Microglia have increasingly been recognized as playing a wide spectrum of roles
      in various physiological and pathological processes in the central nervous
      system. Studies in the past have mostly associated individual microglial enzymes
      or soluble factors such as cytokines with specific functions of microglia. Stable
      isotope labeling with amino acids in cell culture (SILAC)-based proteomic
      analysis enables an unbiased, simultaneous, and global-scale analysis of the
      expression of thousands of proteins involved in key cellular pathways that
      regulate microglial activities. Primary microglia, characteristically, bear a
      much greater resemblance to microglia in vivo than immortalized microglial cell
      lines. In this chapter, we provide a detailed protocol for a de novo and
      uninterrupted primary culture SILAC labeling strategy (DUP-SILAC) for primary rat
      microglia that could be applied to the analysis of microglial involvement in
      various normal and disease processes.

PMID- 28508369
TI  - Spike-In SILAC Approach for Proteomic Analysis of Ex Vivo Microglia.
AB  - Stable isotope labeling by amino acids in cell culture (SILAC) is a versatile
      mass spectrometry-based proteomic approach that can achieve accurate relative
      protein quantitation on a global scale. In this approach, proteins are labeled
      while being synthesized by the cell due to the presence of certain amino acids
      exclusively as heavier mass analogs than their regular (light) counterparts. This
      differential labeling allows for the identification of heavy and light forms of
      each peptide corresponding to two or more different experimental groups upon mass
      spectrometric analysis, the intensities of which reflect their abundance in the
      sample analyzed. Relative quantitation is straightforward when SILAC labeling
      efficiency is high (>99%) and the same cell proteome is used as the quantitation
      reference, which is typically the case for immortalized cell lines. However, the
      SILAC methodology for the proteomic analysis of primary cells isolated after in
      vivo experimentation is more challenging given the low labeling efficiency that
      would be achieved post-isolation. Alternatively, a stable-isotope-labeled cell
      line representing the cell type can be used as an internal standard (spike-in
      SILAC); however, adequate representation of the primary cell proteome with the
      stable-isotope-labeled internal standard may limit overall protein quantitation,
      especially for cell types that exhibit a broad range of phenotypes such as
      microglia, the resident immune cells in the brain. Here, we present a way to
      circumvent this limitation by combining multiple phenotypes of a single-cell type
      (the immortalized mouse BV2 microglial cell line) into a single spike-in standard
      using primary mouse microglia as our model system. We describe the preparation of
      media, incorporation of labels, induction of four different activation states
      (plus resting), isolation of primary microglia from adult mice brains,
      preparation of lysates for analysis, and general guidelines for data processing.

PMID- 28508370
TI  - A Proteomic Evaluation of Sympathetic Activity Biomarkers of the Hypothalamus
      Pituitary-Adrenal Axis by Western Blotting Technique Following Experimental
      Traumatic Brain Injury.
AB  - Endocrine disorders and autonomic dysfunction are common paradigms following
      traumatic brain injury (TBI). Alterations in the hypothalamus-pituitary-adrenal
      (HPA) axis following TBI may result in impaired vasopressor response, energy
      imbalance, fatigue, depression, or neurological disorders. Autonomic dysfunction
      is a common disorder following TBI. The sympathetic activity markers on HPA axis
      can be measured by Western blot protein analysis. Tyrosine hydroxylase, dopamine
      beta hydroxylase are the key enzymes for the synthesis of norepinephrine; and
      neuropeptide Y (NPY) is the peptide that is co-stored and co-released with
      norepinephrine. Thus, the present chapter reviews the experimental protocols for
      Western blot protein analysis for the measurement of biomarkers that indicate
      sympathetic activity in brain regions (hypothalamus, pituitary, cerebral cortex,
      and cerebellum) following TBI.

PMID- 28508371
TI  - Efficient and Accurate Algorithm for Cleaved Fragments Prediction (CFPA) in
      Protein Sequences Dataset Based on Consensus and Its Variants: A Novel
      Degradomics Prediction Application.
AB  - Degradomics is a novel discipline that involves determination of the
      proteases/substrate fragmentation profile, called the substrate degradome, and
      has been recently applied in different disciplines. A major application of
      degradomics is its utility in the field of biomarkers where the breakdown
      products (BDPs) of different protease have been investigated. Among the major
      proteases assessed, calpain and caspase proteases have been associated with the
      execution phases of the pro-apoptotic and pro-necrotic cell death, generating
      caspase/calpain-specific cleaved fragments. The distinction between calpain and
      caspase protein fragments has been applied to distinguish injury mechanisms.
      Advanced proteomics technology has been used to identify these BDPs
      experimentally. However, it has been a challenge to identify these BDPs with high
      precision and efficiency, especially if we are targeting a number of proteins at
      one time. In this chapter, we present a novel bioinfromatic detection method that
      identifies BDPs accurately and efficiently with validation against experimental
      data. This method aims at predicting the consensus sequence occurrences and their
      variants in a large set of experimentally detected protein sequences based on
      state-of-the-art sequence matching and alignment algorithms. After detection, the
      method generates all the potential cleaved fragments by a specific protease. This
      space and time-efficient algorithm is flexible to handle the different
      orientations that the consensus sequence and the protein sequence can take before
      cleaving. It is O(mn) in space complexity and O(Nmn) in time complexity, with N
      number of protein sequences, m length of the consensus sequence, and n length of
      each protein sequence. Ultimately, this knowledge will subsequently feed into the
      development of a novel tool for researchers to detect diverse types of selected
      BDPs as putative disease markers, contributing to the diagnosis and treatment of
      related disorders.

PMID- 28508372
TI  - Effect of Second-Hand Tobacco Smoke on the Nitration of Brain Proteins: A Systems
      Biology and Bioinformatics Approach.
AB  - Second-hand smoke (SHS) exposure leads to the death of approximately 48,000
      nonsmokers per year in the United States alone. SHS exposure has been associated
      with cardiovascular, respiratory, and neurodegenerative diseases. While cardiac
      function abnormalities and lung cancer due to SHS have been well characterized,
      brain injury due to SHS has not undergone a full systematic evaluation. Oxidative
      stress and nitration have been associated with smoking and SHS exposure. Animal
      studies suggest that exposure to tobacco smoke increases oxidative stress.
      Oxidative stress is characterized by an increase in reactive oxygen and nitrogen
      species (ROS/RNS). Among the oxidative mechanisms affecting protein functionality
      is the posttranslational modification (PTM)-mediated tyrosine nitration. Protein
      tyrosine nitration, a covalent posttranslational modification, is commonly used
      as a marker of cellular oxidative stress associated with the pathogenesis of
      several neurodegenerative diseases. In our previous published work, the utility
      of a targeted proteomic approach has been evaluated to identify two brain
      abundant proteins in an in vivo SHS rat model namely the GAPDH and UCH-L1. In
      this current study, mass spectrometric-based proteomic and complementary
      biochemical methods were used to characterize the SHS-induced brain nitroproteome
      followed by bioinformatics/systems biology approach analysis to characterize
      protein interaction map. Sprague Dawley rats were exposed to SHS for 5 weeks and
      then cortical tissues were collected. Nitroprotein enrichment was performed via 3
      Nitro tyrosine (3-NT) immunoprecipitation of brain lysates proteins. Protein
      nitration was validated via Western blotting to confirm the presence of
      nitroproteins complemented by gel-free neuroproteomic analysis by data-dependent
      LC-MS/MS. We identified 29 differentially expressed proteins in the 3-NT-enriched
      samples; seven of these proteins were unique to SHS exposure. Network analysis
      revealed an association of the proteins to different cellular processes including
      oxidative stress, ROS generation, and cell death-related pathway. This confirms
      the association of oxidative stress mechanisms with SHS which may contribute to
      neuronal injury, an area that has not been well studied in the area smoking.

PMID- 28508373
TI  - An Advanced Omic Approach to Identify Co-Regulated Clusters and Transcription
      Regulation Network with AGCT and SHOE Methods.
AB  - To obtain the global picture of genetic machinery for massive high-throughput
      gene expression data, novel data-driven unsupervised learning approaches are
      becoming essentially important. For this purpose, basic analytic workflow has
      been established and should include two steps: first, unsupervised clustering to
      identify genes with similar behavior upon exposure to a signal, and second,
      identification of transcription factors regulating those genes. In this chapter,
      we will describe an advanced tool that can be used for analyzing and
      characterizing large-scale time-series gene expression composed of a two-step
      approach. For the first step, we developed an original method "A Geometric
      Clustering Tool" (AGCT) that unveils the complex architecture of large-scale time
      series gene expression data in a real-time manner using cutting edge techniques
      of low dimension manifold learning, data clustering, and visualization. For the
      second step, we established an original method "Sequence Homology in Eukaryotes"
      (SHOE) executing comparative genomic analysis on humans, mice, and rats.

PMID- 28508374
TI  - AutoDock and AutoDockTools for Protein-Ligand Docking: Beta-Site Amyloid
      Precursor Protein Cleaving Enzyme 1(BACE1) as a Case Study.
AB  - Computational docking and scoring techniques have revolutionized structural
      bioinformatics by providing unprecedented insights on key aspects of ligand
      receptor interaction. Docking is used for optimizing known drugs and for
      identifying novel binders by predicting their binding mode and affinity. AutoDock
      and AutoDockTools are free of charge techniques that have been extensively cited
      in the literature as essential tools in structure-based drug design. Moreover,
      these methods are fast enough to permit virtual screening of ligand libraries
      containing tens of thousands of compounds. However using Autodock requires some
      knowledge in programming which creates a limitation for biologists and makes them
      prone for commercial applications. Here, we selected a relevant target involved
      in the progression of Alzheimer disease and provided a fully reproducible docking
      protocol. This example will show how docking techniques would be an important
      asset to identify new BACE1 inhibitors. The following friendly user tutorial
      targets both undergraduate and graduate students, allowing them to understand
      docking as a computational tool for structure-based drug design.

PMID- 28508375
TI  - An Integration of Decision Tree and Visual Analysis to Analyze Intracranial
      Pressure.
AB  - In Traumatic Brain Injury (TBI), elevated Intracranial Pressure (ICP) causes
      severe brain damages due to hemorrhage and swelling. Monitoring ICP plays an
      important role in the treatment of TBI patients because ICP is considered a
      strong predictor of neurological outcome and a potentially amenable method to
      treat patients. However, it is difficult to predict and measure accurate ICP due
      to the complex nature of patients' clinical conditions. ICP monitoring for severe
      TBI patient is a challenging problem for clinicians because traditionally known
      ICP monitoring is an invasive procedure by placing a device inside the brain to
      measure pressure. Therefore, ICP monitoring might have a high infection risk and
      cause medical complications. In here, an ICP monitoring using texture features is
      proposed to overcome this limitation. The combination of image processing methods
      and a decision tree algorithm is utilized to estimate ICP of TBI patients
      noninvasively. In addition, a visual analytics tool is used to conduct an
      interactive visual factor analysis and outlier detection.

PMID- 28508377
TI  - Emulsion versus nanoemulsion: how much is the formulative shift critical for a
      cosmetic product?
AB  - The use of nanoemulsions in cosmetic products has been enlarged in the last
      decades because of several formulative advantages (e.g., the improved self-life
      stability, better texture properties). In addition, nanoemulsions seemed to
      improve the penetration of active ingredients through the human skin, comparing
      to conventional emulsion. In this contest, the risk of a higher systemic exposure
      of consumer to active ingredients, due to the ability of nanoemulsion to enhance
      permeation, results a critical attribute that should be evaluated for assuring
      the consumer safety. The aim of this work was the evaluation of how an oil-in
      water (O/W) nanoemulsion can influence the in vitro skin permeation profiles of
      two model active ingredients with different polarity (i.e., caffeine and ethyl
      ximenynate). Preliminarily, since both selected molecules influenced the physical
      stability of nanoemulsion, formulative studies were carried out to identify the
      most stable formulation to perform in vitro permeation studies. The overall
      results demonstrated that nanoemulsions could significantly influence the
      permeation profiles of molecules as a function of their physicochemical
      properties. In particular, O/W nanoemulsions significantly improved the
      permeation profiles of apolar active ingredients in comparison to conventional
      emulsions, whereas no differences were observable for polar molecules.
      Considering such findings, it is worth observing that there is room for
      reconsidering the risk assessment of nanoemulsion-based cosmetic products.

PMID- 28508378
TI  - Population Pharmacokinetic and Pharmacodynamic Modeling of Etelcalcetide in
      Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving
      Hemodialysis.
AB  - INTRODUCTION: Etelcalcetide is a novel calcimimetic that binds and activates
      calcium-sensing receptors (CaSRs) for the treatment of secondary
      hyperparathyroidism (SHPT). METHODS: To assess titrated dosing regimens,
      population pharmacokinetic (PK) and PK/pharmacodynamic (PKPD) modeling of
      etelcalcetide was performed using NONMEM 7.2. In this analysis, plasma
      etelcalcetide, serum parathyroid hormone (PTH) and calcium (Ca) concentration
      time data were collected from five phase I, II, and III clinical trials following
      single or multiple intravenous doses of etelcalcetide ranging from 2.5 to 60 mg.
      A semi-mechanistic model was used to describe the relationship between
      etelcalcetide, PTH, and Ca. This model included the role of PTH in Ca regulation,
      the feedback of Ca onto PTH production via the CaSR, and the activity of
      etelcalcetide plasma levels in increasing the sensitivity of the CaSR to Ca via
      the cooperative binding model. The impact of relevant covariates was evaluated by
      stepwise forward/backward selection. Model evaluation was based on standard
      goodness-of-fit plots and prediction-corrected visual predictive checks (pcVPCs).
      Simulation was conducted to evaluate titrated dosing regimens. RESULTS AND
      DISCUSSION: The time courses of etelcalcetide, PTH, and Ca were well-described by
      the model. The clearance and central volume of distribution (Vc) of etelcalcetide
      were 0.472 L/h and 49.9 L, respectively, while estimates of the turnover half
      lives of PTH and Ca were 0.36 and 23 h, respectively. The extent of
      interindividual variability in model parameters was low to moderate (6-67%), and
      no covariates were identified as significant predictors of PK and PD variability.
      pcVPCs confirmed the predictive ability of the model. CONCLUSIONS: The current
      analysis confirms the putative mechanism of action of etelcalcetide as an
      allosteric activator of CaSR. Simulations showed that dose titration of
      etelcalcetide, rather than fixed dose, is needed to effectively decrease the PTH
      level in patient populations.

PMID- 28508376
TI  - In vivo and qualitative studies investigating the translational potential of
      microneedles for use in the older population.
AB  - Microneedles (MNs) are a novel transdermal drug delivery platform, rapidly
      progressing from a substantive evidence base, towards commercialisation. As part
      of this transition, it is important to consider the future use of MNs by older
      people in order to ensure optimal therapeutic outcomes for this unique and
      increasing population group. This paper, therefore, considers the use of MNs by
      those aged over 65 years, investigating insertion parameters in ageing skin,
      alongside the feasibility and acceptability of the technology. Hydrogel-forming
      MN arrays were applied to seven subjects aged over 65 years, with breach of the
      stratum corneum confirmed using optical coherence tomography. Insertion depths
      recorded in each case were similar to a comparative group, aged 20-30 years. Skin
      recovery was, however, demonstrated to occur at a slower rate in the older
      subjects, as measured using transepidermal water loss. Qualitative methods,
      including focus groups and semi-structured interviews, were employed to collect
      the views and opinions of older people and community pharmacists respectively.
      The overall consensus was positive, with a number of benefits to MN-mediated drug
      delivery identified, such as reduced dosing frequency, improved adherence and an
      alternative delivery route where oral or injectable medication was precluded.
      Concerns centred on practical issues associated with age-related functional
      decline, including, for example, reduced dexterity and skin changes. The
      presentation of this work collectively provides the first convincing report of
      the importance of further translational research in this area to support future
      MN use in older people, ensuring an age-appropriate delivery platform.

PMID- 28508379
TI  - [Retinal pigment epithelial detachment in hyperviscosity syndrome].
AB  - We present a case of a 57-year-old woman who reported bilateral visual impairment
      since 2 weeks. She had a medical history of congenital, cyanotic heart failure.
      Funduscopic examination revealed serous retinal detachment on the left side,
      central subneurosensory detachment on the right side, retinal vessel tortuosity
      and multiple retinal haemorrhages in the periphery. As blood analysis showed a
      distinct increase in haemoglobin and haematocrit, hyperviscosity syndrome was
      suspected to have caused bilateral serous retinal detachment. Isovolemic
      haemodilution was performed in close cooperation with the cardiology department
      with repeated phlebotomy, which resulted in a significant reduction of subretinal
      fluid and, concurrently, an increase in visual acuity.

PMID- 28508380
TI  - [Optical coherence tomography in eyes with senile retinoschisis : SD-OCT versus
      ultrasound examinations and assessment of the vitreoretinal interface].
AB  - BACKGROUND: In addition to ocular ultrasonography (US), spectral domain optical
      coherence tomography (SD-OCT) is available in order to diagnose senile
      retinoschisis (sRS). SD-OCT also allows for classification of posterior vitreous
      detachment (PVD) in healthy eyes. OBJECTIVES: Reevaluation of the value and
      additional benefit of both imaging procedures. SD-OCT-based evaluation of PVD
      stages in sRS patients. MATERIALS AND METHODS: Diagnostic results of 33 eyes in
      26 patients with clinical suspicion of sRS were retrospectively analysed. All
      patients received a SD-OCT and a 10 MHz US examination of the region of interest
      (RoI). In 32 eyes the PVD stage was classified by SD-OCT using the description by
      Uchino et al. The vitreous position in peripheral SD-OCT scans with sRS was
      reviewed. RESULTS: SD-OCT confirmed sRS in 29 eyes. US examination identified sRS
      in 26 eyes. In 11 eyes, the examination results of the two methods differed. In 7
      eyes sRS was identified by SD-OCT but not by US examination. US examination
      confirmed sRS in 4 eyes for which SD-OCT scans were not useful. Most cases of sRS
      were detected in temporal located retinal lesions. There was no significant
      difference between the results of both imaging procedures regarding the RoI (p =
      0.64). SD-OCT provided additional information in 27 eyes. Four eyes did not
      present PVD. Early and intermediate stages of PVD were detected in 9 eyes, while
      19 eyes showed complete PVD. In most cases, the vitreous could not be identified
      in the SD-OCT scans of the periphery. CONCLUSIONS: In clinical practice, neither
      SD-OCT nor US ensure an explicit finding of sRS in each eye with sRS. However,
      both methods positively complement one another and together they improve image
      based diagnosis. All stages of PVD may be found in eyes with sRS. The
      contribution of the vitreous to the pathogenesis of sRS remains uncertain.

PMID- 28508382
TI  - Think fast: rapid assessment of the effects of episodic future thinking on delay
      discounting in overweight/obese participants.
AB  - Accumulating laboratory-based evidence indicates that reducing delay discounting
      (devaluation of delayed outcomes) with the use of episodic future thinking (EFT;
      mental simulation of future events) improves dietary decision-making and other
      maladaptive behaviors. Recent work has adapted EFT for use in the natural
      environment to aid in dietary and weight control by engaging participants in EFT
      repeatedly throughout the day. These efforts may benefit from minimizing the
      amount of time required for measurement and implementation of EFT. Using Amazon
      Mechanical Turk in the present study, we show that EFT effectively reduces delay
      discounting in overweight/obese participants (N = 131) using the recently
      developed 5-trial, adjusting-delay discounting task, which can be completed
      rapidly (25 s) and is therefore ideally suited for ecological momentary
      assessment. Moreover, measures of delay discounting from this task were strongly
      correlated with those from the commonly used adjusting-amount task (r = .859).
      Significant effects of EFT on discounting, however, depended on the number of
      future events participants generated and imagined. Use of a range of events and
      future time frames (as is typical in the literature) significantly reduced delay
      discounting, whereas use of only a single event did not.

PMID- 28508381
TI  - Visualization of metallodrugs in single cells by secondary ion mass spectrometry
      imaging.
AB  - Secondary ion mass spectrometry, including nanoscale secondary ion mass
      spectrometry (NanoSIMS) and time-of-flight secondary ion mass spectrometry (ToF
      SIMS), has emerged as a powerful tool for biological imaging, especially for
      single cell imaging. SIMS imaging can provide information on subcellular
      distribution of endogenous and exogenous chemicals, including metallodrugs, from
      membrane through to cytoplasm and nucleus without labeling, and with high spatial
      resolution and chemical specificity. In this mini-review, we summarize recent
      progress in the field of SIMS imaging, particularly in the characterization of
      the subcellular distribution of metallodrugs. We anticipate that the SIMS imaging
      method will be widely applied to visualize subcellular distributions of drugs and
      drug candidates in single cells, exerting significant influence on early drug
      evaluation and metabolism in medicinal and pharmaceutical chemistry. Recent
      progress of SIMS applications in characterizing the subcellular distributions of
      metallodrugs was summarized.

PMID- 28508385
TI  - Improving the temperature characteristics and catalytic efficiency of a
      mesophilic xylanase from Aspergillus oryzae, AoXyn11A, by iterative mutagenesis
      based on in silico design.
AB  - To improve the temperature characteristics and catalytic efficiency of a
      glycoside hydrolase family (GHF) 11 xylanase from Aspergillus oryzae (AoXyn11A),
      its variants were predicted based on in silico design. Firstly, Gly21 with the
      maximum B-factor value, which was confirmed by molecular dynamics (MD) simulation
      on the three-dimensional structure of AoXyn11A, was subjected to site-saturation
      mutagenesis. Thus, one variant with the highest thermostability, AoXyn11AG21I,
      was selected from the mutagenesis library, E. coli/Aoxyn11A G21X (X: any one of
      20 amino acids). Secondly, based on the primary structure multiple alignment of
      AoXyn11A with seven thermophilic GHF11 xylanases, AoXyn11AY13F or AoXyn11AG21I
      Y13F, was designed by replacing Tyr13 in AoXyn11A or AoXyn11AG21I with Phe.
      Finally, three variant-encoding genes, Aoxyn11A G21I, Aoxyn11A Y13F and Aoxyn11A
      G21I-Y13F, were constructed by two-stage whole-plasmid PCR method, and expressed
      in Pichia pastoris GS115, respectively. The temperature optimum (T opt) of
      recombinant (re) AoXyn11AG21I-Y13F was 60  degrees C, being 5  degrees C higher
      than that of reAoXyn11AG21I or reAoXyn11AY13F, and 10  degrees C higher than that
      of reAoXyn11A. The thermal inactivation half-life (t 1/2) of reAoXyn11AG21I-Y13F
      at 50  degrees C was 240 min, being 40-, 3.4- and 2.5-fold longer than those of
      reAoXyn11A, reAoXyn11AG21I and reAoXyn11AY13F. The melting temperature (T m)
      values of reAoXyn11A, reAoXyn11AG21I, reAoXyn11AY13F and reAoXyn11AG21I-Y13F were
      52.3, 56.5, 58.6 and 61.3  degrees C, respectively. These findings indicated that
      the iterative mutagenesis of both Gly21Ile and Tyr13Phe improved the temperature
      characteristics of AoXyn11A in a synergistic mode. Besides those, the catalytic
      efficiency (k cat/K m) of reAoXyn11AG21I-Y13F was 473.1 mL mg-1 s-1, which was
      1.65-fold higher than that of reAoXyn11A.

PMID- 28508384
TI  - Endoscopic Management of Benign Esophageal Ruptures and Leaks.
AB  - OPINION STATEMENT: Esophageal leaks (EL) and ruptures (ER) are rare conditions
      associated with a high risk of mortality and morbidity. Historically, EL and ER
      have been surgically treated, but current treatment options also include
      conservative management and endoscopy. Over the last decades, interventional
      endoscopy has evolved as an effective and less invasive alternative to primary
      surgery in these cases. A variety of techniques are currently available to re
      establish the continuity of the digestive tract, prevent or treat infection
      related to the leak/rupture, prevent further contamination, drain potential
      collections, and provide nutritional support. Endoscopic options include clips,
      both through the scope (TTS) and over the scope (OTS), stent placement, vacuum
      therapy, tissue adhesive, and endoscopic suturing techniques. Theoretically, all
      of these can be used alone or with a multimodality approach. Endoscopic therapy
      should be combined with medical therapy but also with percutaneous drainage of
      collections, where present. There is robust evidence suggesting that this change
      of therapeutic paradigm in the form of endoscopic therapy is associated with
      improved outcome, better quality of life, and shortened length of hospital stay.
      Moreover, recent European guidelines on endoscopic management of iatrogenic
      perforation have strengthened and to some degree regulated and redefined the role
      of endoscopy in the management of conditions where there is a breach in the
      continuity of the GI wall. Certainly, due to the complexity of these conditions
      and the variety of available treatment options, a multidisciplinary approach is
      strongly recommended, with close clinical monitoring (by endoscopists, surgeons,
      and intensive care physicians) and special attention to signs of sepsis, which
      can lead to the need for urgent surgical management. This review article will
      critically discuss the literature regarding endoscopic modalities for esophageal
      leak and perforation management and attempt to place them in perspective for the
      physician.

PMID- 28508386
TI  - Application of response surface methodology for optimization of medium components
      for the production of secondary metabolites by Streptomyces diastatochromogenes
      KX852460.
AB  - A bioactive strain Streptomyces diastatochromogenes KX852460 was selected for the
      production of secondary metabolites to control the target spot disease on tobacco
      leaves, caused by the Rhizoctonia solani AG-3. Peanut meal, soluble starch, NaCl,
      yeast extract, and ammonium sulphate were identified the best ingredient for high
      antifungal activity of S. diastatochromogenes KX852460 against the R. solani AG
      3. For the improved production of secondary metabolites, central composite design
      of response surface methodology was applied in submerged fermentation. The best
      concentrations of ingredients were peanut meal 4.88%, soluble starch 4.40%, NaCl
      0.52%, yeast extract 0.47%, and ammonium sulphate 0.0360%. Study of metabolism
      changes in the submerged fermentation process was analyzed. Level of the reducing
      sugar increased, as the total sugar consumed. Amino nitrogen and total sugar
      decrease tendency, which indicated the growth of bacteria in submerged
      fermentation batch. Production of secondary and other metabolites influenced the
      pH of the fermentation batch.

PMID- 28508387
TI  - No evidence for induction of autoantibodies or autoimmunity during treatment of
      psoriasis with ustekinumab.

PMID- 28508383
TI  - Spiritual well-being, religious activity, and the metabolic syndrome: results
      from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary
      Study.
AB  - Sociocultural risk and protective factors for developing the metabolic syndrome
      (MetS), a risk factor for cardiovascular disease (CVD), have not been well
      studied in Hispanics/Latinos residing in the United States (U.S.). Religiosity
      and/or spirituality (R/S), important aspects of Hispanic/Latino culture, have
      been inversely associated with CVD and multiple CVD risk factors. Cross-sectional
      associations between dimensions of R/S and prevalent MetS, and its five
      individual components were examined using multiple logistic and linear
      regression, among 3278 U.S., middle-aged and older Hispanic/Latino adults from
      the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary
      Study. Dimensions of R/S were not associated with presence of the MetS. Certain
      dimensions of Spiritual Well-being (Meaning, Peace, Faith), and frequency of non
      organizational religious activity were weakly but significantly associated with
      one or more MetS components including waist circumference, diastolic blood
      pressure, and systolic blood pressure. R/S variables were not associated with
      triglycerides, fasting glucose or HDL cholesterol levels. Prospective,
      longitudinal studies are needed to gain a deeper understanding of the nature of
      the relationship between R/S and health risk factors in U.S. Hispanics/Latinos.

PMID- 28508388
TI  - Positive clinical outcome in a patient with recalcitrant bullous pemphigoid
      treated with rituximab and intravenous immunoglobulin.
AB  - A 41-year-old white man was treated for bullous pemphigoid (BP) for 4 years,
      using high-dose prednisone as well as ciclosporin and mycophenolate mofetil.
      Sustained clinical improvement was not observed. He suffered several serious side
      effects. Consequently, he was treated with a combination of rituximab (RTX) and
      intravenous immunoglobulin (IVIg). He received 12 infusions of RTX in 6 months
      and monthly IVIg until the end of the therapy. Within 5 weeks of this therapy,
      appearance of new lesions ceased. Within 8 weeks, all previous lesions resolved
      and previous medications were discontinued. No hospitalizations, relapses,
      infections or other serious adverse events occurred. The high levels of
      pathogenic autoantibody decreased and have remained undetectable. After three
      infusions of RTX, CD19+ B cells were undetectable and returned to normal levels
      within 18 months. The patient remains in complete clinical remission off all
      systemic therapy and free of disease for a 20-month follow-up.

PMID- 28508389
TI  - Usefulness of techniques based on real time PCR for the identification of
      onychomycosis-causing species.
AB  - Onychomycosis (OM) is a nail infection caused mainly by dermatophyte species but
      other species of yeast and moulds are frequently involved as well. Classical
      diagnosis has limitations thus empirical treatment is common. The usefulness of
      different real time PCR (RT-PCR) assays for identifying species causing OM was
      assessed in samples from seventy patients and fifteen controls. Conventional
      methods and four different RT-PCR assays were used: a panfungal, a
      pandermatophyte and two specific assays for detecting Candida spp. and
      Aspergillus spp. Fungal elements were visualised in 58% of the samples, and 54%
      of cultures were positive. Panfungal and pandermatophyte RT-PCR were positive in
      28% and 60%, respectively, and the sensitivity relative to positive cultures was
      47% and 90%. Candida spp. were detected in 76% of samples analysed and
      Aspergillus spp. in 60%. These species were also present in 80% of control cases.
      In conclusion, molecular techniques were useful but showed limitations. The
      panfungal assay showed a low sensitivity, the pandermatophyte assay was sensitive
      and specific but did not allow for differentiation among species of
      dermatophytes. Finally, the role of non-dermatophyte species detected by using
      specific RT-PCR techniques should be carefully analysed as these species were
      also present in healthy nails.

PMID- 28508390
TI  - Elevated maternal placental protein 13 serum levels at term of pregnancy in
      postpartum major hemorrhage (>1000 mLs). A prospective cohort study.
AB  - PROBLEM: To compare placental protein 13 (PP13) levels in the serum of women with
      primary postpartum hemorrhage (PPH) with a control population. METHODS: A
      prospective cohort study was conducted between May 2014 and May 2016 and included
      435 pregnant women at term (38 weeks gestation) without any known risk factor and
      with normal labor. Multiples of median (MoM) were used to evaluate differences of
      the PP13 values between cases and controls. PP13 concentrations were adjusted for
      maternal and neonatal weight. Multivariable analysis was used to detect
      independent contribution of predictors of PPH. RESULTS: Fifteen had a major PPH
      >1000 mLs and represented the cases of the study. They were matched with 399
      controls. Twenty-one patients who had a minor PPH (500-1000 mLs) were excluded.
      The mean observed rank in the PPH group was higher than that of controls (28.5 vs
      13.5, P-value=.01). PP13 MoM values adjusted for maternal weight were higher than
      expected being 1.44+/-0.45 in PPH cases and 1.00+/-0.59 in controls (P-value
      .008). This difference was still significant even after adjustment for neonatal
      weight that represented a confounding variable. CONCLUSION: Higher PP13 levels
      are independently associated with major PPH >1000 mLs.

PMID- 28508391
TI  - Burkitt lymphoma.

PMID- 28508392
TI  - Polyoxometalate-Engineered Building Blocks with Gold Cores for the Self-Assembly
      of Responsive Water-Soluble Nanostructures.
AB  - The controlled assembly of gold nanoparticles (AuNPs) with the size of quantum
      dots into predictable structures is extremely challenging as it requires the
      quantitatively and topologically precise placement of anisotropic domains on
      their small, approximately spherical surfaces. We herein address this problem by
      using polyoxometalate leaving groups to transform 2 nm diameter gold cores into
      reactive building blocks with hydrophilic and hydrophobic surface domains whose
      relative sizes can be precisely tuned to give dimers, clusters, and larger
      micelle-like organizations. Using cryo-TEM imaging and 1 H DOSY NMR spectroscopy,
      we then provide an unprecedented "solution-state" picture of how the micelle-like
      structures respond to hydrophobic guests by encapsulating them within 250 nm
      diameter vesicles whose walls are comprised of amphiphilic AuNP membranes. These
      findings provide a versatile new option for transforming very small AuNPs into
      precisely tailored building blocks for the rational design of functional water
      soluble assemblies.

PMID- 28508393
TI  - Reversed single string technique for coronary bifurcation stenting-First report
      of case demonstrations in vitro.
AB  - OBJECTIVES: This work reports the concept and the practical feasibility of
      Reversed Single String bifurcation stenting technique by demonstrating three in
      vitro cases. BACKGROUND: Provisional T stenting is the most used interventional
      technique to treat coronary bifurcation lesions. However, after main branch (MB)
      stenting, treatment of the side branch (SB) may become indicated to provide a
      good final result. Currently applied methods all have their structural
      limitations with respect to wall coverage, multiple strut layers, poor apposition
      rate. We reasoned that reversing the Single String technique principle could be
      used as a bail out after inadequate provisional T stenting. METHODS AND RESULTS:
      We simulated in three silicone bifurcation phantoms a scenario whereby stenting
      the SB becomes indicated after provisional T stenting. Thereafter, as first step
      of Reversed Single String, a stent was deployed into the SB ostium with one
      single protruding stent-cell into the MB. After wiring that stent-cell and
      positioning MB balloon across it, final kissing balloon dilation was performed.
      Results of the in vitro Reversed Single String cases were evaluated by X-ray
      angiography, optical frequency domain imaging, and 3-Dimensional (3D)
      reconstruction (OFDI). Each case was successfully performed and completed. In the
      bifurcation area, perfect apposition was documented in over 81% of the struts.
      Malapposition remained below 4% of struts in each case. 3D OFDI reconstruction
      did not reveal any strut fracture. CONCLUSION: This report suggests that Reversed
      Single String technique might offer a potential bail out solution for provisional
      T-stenting cases, when treatment of the SB becomes indicated. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28508395
TI  - Reiteration of the Statistical Basis of DNA Source Attribution Determinations in
      View of the Attorney General's Directive on "Reasonable Scientific Certainty"
      Statements.

PMID- 28508394
TI  - Disentangling the effects of date, individual, and territory quality on the
      seasonal decline in fitness.
AB  - The seasonal timing of reproduction is a major fitness factor in many organisms.
      Commonly, individual fitness declines with time in the breeding season. We
      investigated three suggested but rarely tested hypotheses for this seasonal
      fitness decline: (1) time per se (date hypothesis), (2) late breeders are of
      lower quality than early ones (individual quality hypothesis), and (3) late
      breeders are breeding at poorer territories than early breeders (territory
      quality hypothesis). We used Bayesian variance component analyses to examine
      reproductive output (breeding success, number fledged, and number of recruits)
      from repeated observations of female Northern Wheatears (Oenanthe oenanthe) and
      individual territories from a 20-yr population study. The major part of the
      observed seasonal decline in reproductive output seemed to be driven by date
      related effects, whereas female age and territory type (i.e., known indicators of
      temporary quality) contributed to a smaller degree. Other, persistent effects
      linked to individual and territory identity did not show any clear patterns on
      the seasonal decline in reproductive output. To better disentangle the quality
      effects (persistent and temporary) of individual and territory from effects
      caused by the deterioration of the environment we suggest a protocol combining
      experimental manipulation of breeding time with a variance-covariance
      partitioning method used here.

PMID- 28508396
TI  - Three-Year-Olds' Reactions to a Partner's Failure to Perform Her Role in a Joint
      Commitment.
AB  - When children make a joint commitment to collaborate, obligations are created.
      Pairs of 3-year-old children (N = 144) made a joint commitment to play a game. In
      three different conditions the game was interrupted in the middle either because:
      (a) the partner child intentionally defected, (b) the partner child was ignorant
      about how to play, or (c) the apparatus broke. The subject child reacted
      differently in the three cases, protesting normatively against defection (with
      emotional arousal and later tattling), teaching when the partner seemed to be
      ignorant, or simply blaming the apparatus when it broke. These results suggest
      that 3-year-old children are competent in making appropriate normative
      evaluations of intentions and obligations of collaborative partners.

PMID- 28508397
TI  - Why is the female population more susceptible to cholestasis-induced liver injury
      Could it be long noncoding RNA H19?

PMID- 28508398
TI  - Effect of electromyographic biofeedback as an add-on to pelvic floor muscle
      exercises on neuromuscular outcomes and quality of life in postmenopausal women
      with stress urinary incontinence: A randomized controlled trial.
AB  - AIMS: To compare the efficacy of pelvic floor muscle exercises (PFME) with and
      without electromyographic biofeedback (BF) in increasing muscle strength,
      improving myoelectric activity, and improving pre-contraction and quality of life
      in postmenopausal women with stress urinary incontinence. METHODS: Randomized
      controlled trial of 49 postmenopausal women with stress urinary incontinence.
      Participants were allocated across three groups: control, PFME alone, and PFME +
      BF. Forty-five women completed the study (14 control, 15 PFME, 16 PFME + BF; mean
      age 58.26 years). Outcome assessment was carried out using digital palpation
      (modified Oxford grading scale), electromyography, and the International
      Consultation Incontinence Questionnaire-Short Form (ICIQ-SF) quality of life
      instrument. The treatment protocol consisted of eight twice-weekly, 20-min one-on
      one sessions. Controls were assessed only at baseline and after 1 month. RESULTS:
      The PFME and PFME + BF groups exhibited significant increases in muscle strength
      (Oxford scale) (P < 0.0001), precontraction while coughing (P < 0.0001), maximum
      voluntary contraction, duration of endurance contraction, and ICIQ-SF scores (P <
      0.0001). PFME + BF was associated with significantly superior improvement of
      muscle strength, precontraction while coughing, maximum voluntary contraction,
      and duration of endurance contraction as compared to PFME alone (P < 0.05).
      CONCLUSIONS: This preliminary study suggests that pelvic floor muscle training,
      with and without biofeedback, is associated with increased muscle strength,
      myoelectric activity, precontraction of pelvic floor muscles, and improved
      quality of life in postmenopausal women with stress urinary incontinence.

PMID- 28508399
TI  - HDlive Flow silhouette mode and spatiotemporal image correlation for diagnosing
      congenital heart disease.

PMID- 28508400
TI  - Vascular endothelial growth factor receptor 3 is a novel marker differing CD138
      positive and CD138-negative multiple myeloma cells.

PMID- 28508401
TI  - Oxygen-Deficient Titanium Dioxide Nanosheets as More Effective Polysulfide
      Reservoirs for Lithium-Sulfur Batteries.
AB  - In this work, oxygen-deficient anatase TiO2 nanosheets (A-TiO2-x NSs) are
      proposed as a substrate to improve the electrochemical properties of sulfur
      electrodes for lithium-sulfur (Li-S) batteries. The A-TiO2-x NSs are prepared by
      partly reducing pristine TiO2 nanosheets (A-TiO2 NSs) in NaBH4 solution. With
      some oxygen vacancies on the surface of the TiO2 nanosheets, A-TiO2-x NSs not
      only promote electronic transfer, but also act as more effective polysulfide
      reservoirs to minimize the dissolution of lithium polysulfides (LiPSs) than the A
      TiO2 NSs control. Hence, upon utilization as modifiers for cathodes of Li-S
      batteries, the A-TiO2-x NSs-modified sulfur (A-TiO2-x NSs-S) cathode exhibits a
      higher reversible specific capacity and greater cycling performance and rate
      capability than the A-TiO2 NSs-modified one (A-TiO2 NSs-S). For example, A-TiO2-x
      NSs-S delivers an initial specific capacity of 1277.1 mAh g-1 at 0.1 C and
      maintains a stable Coulombic efficiency of approximately 99.2 % after the first
      five cycles; these values are higher than those of 997.3 mAh g-1 and around 96.7
      %, respectively, for A-TiO2 NSs-S. The enhanced electrochemical properties of the
      A-TiO2-x NSs-S cathode can be ascribed mainly to the more effective adsorption of
      dissolvable and diffused LiPSs by the oxygen vacancies. Therefore, utilization of
      the structure of oxygen vacancies in Li-S batteries demonstrates great prospects
      for practical application.

PMID- 28508402
TI  - Risk factors for human immunodeficiency virus among blood donors in Cameroon:
      evidence for the design of an Africa-specific donor history questionnaire.
AB  - BACKGROUND: In sub-Saharan Africa improving the deferral of at-risk blood donors
      would be a cost-effective approach to reducing transfusion-transmitted human
      immunodeficiency virus (HIV) infections. We performed a pilot case-control study
      to identify the risk factors for HIV infection and to develop an adapted donor
      history questionnaire (DHQ) for sub-Saharan Africa. STUDY DESIGN AND METHODS: We
      recruited 137 HIV-positive donors (cases) and 256 HIV-negative donors (controls)
      and gathered risk factor data using audio computer-assisted self-interview.
      Variables with univariate associations were entered into a logistic regression
      model to assess independent associations. A scoring scheme to distinguish between
      HIV-positive and HIV-negative donors was developed using receiver operating
      characteristics curves. RESULTS: We identified 16 risk factors including sex with
      sex worker, past history or treatment for sexually transmitted infections, and
      having a partner who used injected or noninjected illegal drugs. Two novel risks
      were related to local behavior: polygamy (odds ratio [OR], 22.7; 95% confidence
      interval [CI], 5.9-86.7) and medical or grooming treatment on the street (OR,
      1.8; 95% CI, 1.0-3.0). Using the 16 selected items the mean scores (>100) were
      82.6 +/- 6.7 (range, 53.2-95.1) and 85.1 +/- 5.2 for HIV-negative donors versus
      77.9 +/- 6.8 for HIV-positive ones (p = 0.000). Donors who scored between 80 and
      90 were more likely to be HIV negative than those who scored less (OR, 31.4; 95%
      CI, 3.1-313.9). CONCLUSION: We identified both typical and novel HIV risk factors
      among Cameroonian blood donors. An adapted DHQ and score that discriminate HIV
      negative donors may be an inexpensive means of reducing transfusion-transmitted
      HIV through predonation screening.

PMID- 28508403
TI  - Physiochemical and functional properties of chum salmon (Oncorhynchus keta) skin
      gelatin extracted at different temperatures.
AB  - BACKGROUND: Aquatic source gelatins are gaining more attention due to the
      advantages in safety and religion acceptability compared with mammalian sources.
      For understanding the effects of extracting temperature on gelatins from chum
      salmon (Oncorhynchus keta) skins (GCSS), gelatins were extracted at temperatures
      from 40 to 90 degrees C and the physiochemical properties of GCSS were
      investigated. RESULTS: GCSS yield increased while imino acids content declined as
      the increase of temperature. GCSS40, 50 and 60 showed strong beta-, alpha1- and
      alpha2-chains but the three faded in GCSS70, 80 and 90, with the presence of low
      molecular weight fragments. Amides A, I and III were shifted to higher wavenumber
      in GCSS70, 80 and 90 compared with that of GCSS40, 50 and 60. X-ray diffraction
      showed lower intensity of peak at 7 degrees  in GCSS80 and 90 than in the other
      GCSS. Gel strength declined while a*, b* and DeltaE* value increased as
      temperature increased. Foam expansion and stability of GCSS40, 50 and 60 were
      lower than those of GCSS70, 80 and 90. Emulsion activity and stability decreased
      as temperature increased. CONCLUSION: Extracting temperature greatly affected
      yield, molecular composition and functionalities of GCSS. A temperature lower
      than 50 degrees C is recommended for GCSS extraction. (c) 2017 Society of
      Chemical Industry.

PMID- 28508404
TI  - Changes in biomechanics of skiing at maximal velocity caused by simulated 20-km
      skiing race using V2 skating technique.
AB  - This study investigated how the fatigue caused by a 20-km simulated skating cross
      country skiing race on snow affects the final spurt performance from a
      biomechanical perspective. Subjects performed a 100-m maximal skiing trial before
      and at the end of the simulated race. Cycle characteristics, ground reaction
      forces from skis and poles, and muscle activity from eight muscles were recorded
      during each trial. Results showed that subjects were in a fatigued state after
      the simulated race manifested by 11.6% lower skiing speed (P<.01). The lower
      skiing speed was related to an 8.0% decrease in cycle rate (P<.01), whereas cycle
      length was slightly decreased (tendency). In temporal patterns, relative kick
      time was increased (10.9%, P<.01) while relative poling time was slightly
      decreased (tendency). Vertical ski force production decreased by 8.3% while pole
      force production decreased by 26.0% (both, P<.01). Muscle activation was
      generally decreased in upper (39.2%) and lower body (30.7%) (both, P<.01).
      Together these findings show different responses to fatigue in the upper and
      lower body. In ski forces, fatigue was observed via longer force production times
      while force production levels decreased only slightly. Pole forces showed equal
      force production times in the fatigued state while force production level
      decreased threefold compared to the ski forces.

PMID- 28508405
TI  - Detection of cytological changes in oral mucosa among users of smokeless tobacco
      (shamma) in the KSA.
AB  - BACKGROUND AND AIM: Smokeless tobacco (ST) use is a major cause of cytological
      changes in the oral mucosa. ST products, such as shamma, which is prevalent in
      southern Saudi Arabia, raise concerns about the adverse health effects among its
      users. We evaluated the cytological changes in the oral mucosa of users and
      nonusers of shamma in the city of Najran, using Papanicolaou staining. MATERIALS
      AND METHODS: We designed questionnaires and consent forms for this study that
      were administered to a total of 397 participants, comprising 250 nonusers of
      shamma (controls) and 147 shamma users (cases). Buccal cell smears were collected
      from all participants, fixed, and Papanicolaou stained. Photomicrographs were
      taken of all stained smears, and samples were subsequently diagnosed. RESULTS:
      Various cytological changes were detected among both cases and controls: atypia
      (2.0%, 1.2%, respectively), keratinisation (0.7%, 0%, respectively), inflammation
      (13.6%, 10.8%, respectively), and infection (4.1%, 3.6%, respectively).
      CONCLUSION: The results showed higher percentages of cytological changes among
      shamma users compared with nonusers; however, the differences were not
      statistically significant. Habitual use of other substances in the control group
      could be a confounding factor given this geographic region and the cytological
      changes we detected in both cases and controls. Diagn. Cytopathol. 2017;45:693
      699. (c) 2017 Wiley Periodicals, Inc.

PMID- 28508406
TI  - Hypericum perforatum L. supplementation protects sciatic nerve injury-induced
      apoptotic, inflammatory and oxidative damage to muscle, blood and brain in rats.
AB  - OBJECTIVES: This study was conducted to explore whether Hypericum perforatum L.
      (HPL) as a potent antioxidant protects against oxidative stress, cytokine
      production and caspase expression in muscle (soleus), brain and blood of sciatic
      nerve injury (SNI)-induced rats. METHODS: Thirty-five rats were equally divided
      into five groups. The first and second were used as untreated control and sham
      control groups, respectively. The third, fourth and fifth were sham + HPL, SNI
      and SNI + HPL groups, respectively. The third and fifth groups received 30 mg/kg
      HPL via gastric gavage for 28 days. KEY FINDINGS: High levels of muscle, brain
      and red blood cell (RBC) lipid peroxidation, plasma cytokine (TNF-alpha, IL-1beta
      and IL-2), muscle PARP, caspase 3 and 9 expression levels were decreased by HPL
      treatments. Plasma glutathione peroxidase (GPx) activity, alpha-tocopherol and
      melatonin, muscle, brain and RBC reduced glutathione (GSH) concentrations were
      decreased by SNI induction, whereas their values were increased by HPL
      treatments. beta-carotene and retinol concentrations did not change in the five
      groups. CONCLUSION: HPL may play a role in preventing SNI-induced inflammatory,
      oxidative and apoptotic blood, muscle and brain damages through upregulation of
      the GSH and GPx values but downregulation of PARP, caspase level and cytokine
      production in SNI-induced rats.

PMID- 28508408
TI  - Variations in status of preparation of personal protective equipment for
      preventing norovirus gastroenteritis in long-term care facilities for the
      elderly.
AB  - RATIONALE, AIM, AND OBJECTIVES: Residents of long-term care facilities are highly
      susceptible to norovirus gastroenteritis, and each facility is concerned about
      the need to implement norovirus infection control. Among control measures,
      personal protective equipment (PPE), such as disposable gloves and masks, plays a
      major role in reducing infectious spread. However, the preparation status of PPE
      in facilities before infection outbreaks has not been reported. The aim was to
      clarify the implementation status of preventive measures for norovirus
      gastroenteritis and the cost of preparing the necessary PPE in long-term care
      facilities. METHOD: A questionnaire survey of facilities affiliated with the
      Kyoto Prefecture and Osaka Prefecture branches of the Japan Association of
      Geriatric Health Services Facilities was conducted. The survey items were the
      characteristics of the facility, whether preventive measures had been implemented
      for norovirus gastroenteritis from October through the following March in both
      2009 and 2010, and the quantities and unit prices of PPE prepared for preventive
      measures. RESULTS: Twenty-six (11.2%) of 232 surveyed facilities (as of August
      2011) answered the survey. Among them, 24 (92.3%) in 2009 and 25 (96.2%) in 2010
      reported having implemented preventive measures for norovirus gastroenteritis,
      while 21 facilities (80.8%) in 2009 and 22 facilities (84.6%) in 2010 had
      prepared PPE. The median total cost for preparing the PPE needed for the
      preventive measures was US $2601 (range US $221-9192) in 2009 and US $3904 (range
      US $305-6427) in 2010. CONCLUSION: Although the results need careful
      interpretation because of the low response rate, most of the surveyed long-term
      care facilities had implemented preventive measures for norovirus
      gastroenteritis. However, the cost of preparing the PPE needed for the preventive
      measures varied among the facilities.

PMID- 28508409
TI  - Mycobacterium chimaera left ventricular assist device infections.
AB  - A global outbreak of invasive Mycobacterium chimaera infections after cardiac
      surgery has recently been linked to bioaerosols from contaminated heater-cooler
      units. The majority of cases have occurred after valvular surgery or aortic graft
      surgery and nearly half have resulted in death. To date, infections in patients
      with left ventricular assist devices (LVADs) have not been characterized in the
      literature. We report two cases of device-associated M. chimaera infection in
      patients with continuous-flow LVADs and describe challenges related to diagnosis
      and management in this population.

PMID- 28508411
TI  - The relationship between symptom prevalence, body image, and quality of life in
      Asian gynecologic cancer patients.
AB  - OBJECTIVE: Gynecologic cancer is associated with long-term effects that can be
      both physical and emotional. We examined symptom prevalence and body image
      disturbance in patients with gynecologic cancer and their association with
      quality of life. Predictors of clinically-relevant body image disturbance were
      examined. METHODS: A sample of patients in Singapore (n = 104) was assessed for
      symptom prevalence, quality of life, and body image dissatisfaction. Clinical
      factors were extracted from medical records. RESULTS: The most frequently
      reported symptoms were fatigue, abdominal bloatedness, weight gain, constipation,
      hot flashes, and pelvic pain. Approximately one quarter patients reported feeling
      less physically attractive and dissatisfied with their body. Ordinary least
      squares regression indicated that symptom prevalence alone predicted physical
      well-being, b = -1.09, P < .001, 95% CI, -1.45 to -0.73, and functional well
      being, b = -0.88, P < .001, 95% CI, -1.32 to -0.45. Body image dissatisfaction
      alone significantly predicted emotional well-being, b = -0.21, P < .01, 95% CI, 
      0.35 to -0.06. Younger age was a significant risk factor for clinically-relevant
      score of body image distress, OR = 0.95 per year older, 95% CI, 0.92 to 0.99, P =
      .02. CONCLUSIONS: Symptom prevalence and body image dissatisfaction were
      associated with different domains of quality of life. Emotional well-being of
      patients was better explained by body image, rather than extent of symptoms
      experienced. Patients who are younger appear particularly susceptible to body
      image disturbance.

PMID- 28508407
TI  - Structural conservation of the PIN domain active site across all domains of life.
AB  - The PIN (PilT N-terminus) domain is a compact RNA-binding protein domain present
      in all domains of life. This 120-residue domain consists of a central and
      parallel beta sheet surrounded by alpha helices, which together organize 4-5
      acidic residues in an active site that binds one or more divalent metal ions and
      in many cases has endoribonuclease activity. In bacteria and archaea, the PIN
      domain is primarily associated with toxin-antitoxin loci, consisting of a toxin
      (the PIN domain nuclease) and an antitoxin that inhibits the function of the
      toxin under normal growth conditions. During nutritional or antibiotic stress,
      the antitoxin is proteolytically degraded causing activation of the PIN domain
      toxin leading to a dramatic reprogramming of cellular metabolism to cope with the
      new situation. In eukaryotes, PIN domains are commonly found as parts of larger
      proteins and are involved in a range of processes involving RNA cleavage,
      including ribosomal RNA biogenesis and nonsense-mediated mRNA decay. In this
      review, we provide a comprehensive overview of the structural characteristics of
      the PIN domain and compare PIN domains from all domains of life in terms of
      structure, active site architecture, and activity.

PMID- 28508412
TI  - Nicotine withdrawal syndrome in a newborn baby after maternal use of oral applied
      moist tobacco (snus), should result in greater awareness to the use of snus among
      pregnant women.

PMID- 28508410
TI  - Lipid distribution, composition and uptake in bovine articular cartilage studied
      using Raman micro-spectrometry and confocal microscopy.
AB  - The distribution and composition of endogenous lipids in articular cartilage and
      transport of exogenous fatty acids have been investigated on a microscopic scale
      in fresh bovine articular cartilage. To investigate the distribution and
      composition of the endogenous lipids, hyperspectral Raman maps were taken of
      chondrocytes and their surrounding matrix in both the deep and superficial zones.
      These revealed differences in both lipid distribution and composition between the
      two zones. Extracellular lipid was observed surrounding the cells in the
      superficial zone but not in the deep zone. Additionally, intracellular lipid
      droplets were observed that were larger and more numerous in the deep zone (P =
      0.01). The extracellular lipid was primarily free saturated fatty acid, whereas
      the cellular lipid droplets contained triglycerides with unsaturated fatty acid
      chains. Fatty acid uptake and transport were investigated by incubating cartilage
      samples in Dulbecco's modified Eagle's medium containing fluorescently labelled
      palmitate for a range of times and temperatures. After incubation, the palmitate
      distribution was imaged using confocal microscopy. Palmitate accumulated
      preferentially in the territorial matrix only in the superficial zone where the
      concentration was up to 100-fold greater than that in the bulk matrix (P =
      0.001). Palmitate uptake by the chondrocytes in both zones showed differential
      temperature sensitivity (P = 0.05), which would support the idea that cells take
      up palmitate by both active and passive mechanisms. The study reveals large
      differences between chondrocytes in the superficial and deep zones in their lipid
      content, in their extracellular lipid environment and in their access to
      exogenous fatty acids.

PMID- 28508415
TI  - Proptosis secondary to third nerve palsy.

PMID- 28508414
TI  - Cervical cerclage placed before 14 weeks gestation in women with one previous
      midtrimester loss: A population-based cohort study.
AB  - BACKGROUND: Cervical cerclage is used in an attempt to reduce recurrence risk of
      preterm birth, but evidence for use is limited. AIMS: To compare pregnancy
      outcomes among women with a single previous midtrimester delivery when managed
      with or without a cervical cerclage. MATERIALS AND METHODS: Population-based
      cohort study of all women in New South Wales, Australia with a singleton
      pregnancy ending in birth/miscarriage >=14 and <28 weeks, between 2003 and 2011.
      Modified Poisson regression was used to compare outcomes in the next subsequent
      pregnancy, for women with a cerclage inserted <14 weeks, and those without
      cerclage. The primary outcome was gestational age <37 weeks at birth/miscarriage
      in the next pregnancy. Secondary outcomes included: maternal morbidity, preterm
      prelabour rupture of membranes (PPROM), stillbirth/neonatal death and composite
      neonatal morbidity for liveborn infants >=28 weeks. Adjusted risk ratios (ARR)
      and 95% confidence intervals (CI) were determined. RESULTS: Five thousand, six
      hundred and ninety-eight births/miscarriages were potential index deliveries. Of
      these, 2175 women had an eligible subsequent pregnancy: 108 received cerclage at
      <14 weeks gestation, 2067 did not. Women with cerclage were significantly more
      likely to deliver <37 weeks than those without (39.8% vs 19.3%, ARR 1.92, 95% CI
      1.48-2.48), and had increased risks of PPROM (ARR 4.38, 95% CI 2.62-7.32) and
      stillbirth/neonatal death (ARR 2.20, 95% CI 1.02-4.73). Following cerclage,
      liveborn infants >=28 weeks had double the risk of severe morbidity (ARR 2.54,
      95% CI 1.55-4.16). CONCLUSIONS: In women with a single previous midtrimester
      delivery, cervical cerclage <14 weeks gestation in subsequent pregnancy was
      associated with worse pregnancy outcomes.

PMID- 28508413
TI  - Serological weak D phenotypes: a review and guidance for interpreting the RhD
      blood type using the RHD genotype.
AB  - Approximately 0.2-1% of routine RhD blood typings result in a "serological weak D
      phenotype." For more than 50 years, serological weak D phenotypes have been
      managed by policies to protect RhD-negative women of child-bearing potential from
      exposure to weak D antigens. Typically, blood donors with a serological weak D
      phenotype have been managed as RhD-positive, in contrast to transfusion
      recipients and pregnant women, who have been managed as RhD-negative. Most
      serological weak D phenotypes in Caucasians express molecularly defined weak D
      types 1, 2 or 3 and can be managed safely as RhD-positive, eliminating
      unnecessary injections of Rh immune globulin and conserving limited supplies of
      RhD-negative RBCs. If laboratories in the UK, Ireland and other European
      countries validated the use of potent anti-D reagents to result in weak D types
      1, 2 and 3 typing initially as RhD-positive, such laboratory results would not
      require further testing. When serological weak D phenotypes are detected,
      laboratories should complete RhD testing by determining RHD genotypes (internally
      or by referral). Individuals with a serological weak D phenotype should be
      managed as RhD-positive or RhD-negative, according to their RHD genotype.

PMID- 28508416
TI  - Frame-shift variant in the CHRNE gene in a juvenile dog with suspected myasthenia
      gravis-like disease.

PMID- 28508417
TI  - Score of Toxic Epidermal Necrosis Predicts the Outcomes of Pediatric Epidermal
      Necrolysis.
AB  - BACKGROUND/OBJECTIVES: Epidermal necrolysis (Stevens-Johnson syndrome and toxic
      epidermal necrolysis) includes immune-mediated, life-threatening inflammatory
      blistering disorders that can affect children. The Score of Toxic Epidermal
      Necrosis (SCORTEN) tool has accurately predicted the outcome of these disorders
      in adults but has not been tested in children. METHODS: We performed a
      retrospective chart review to compare the accuracy of the adult SCORTEN tool with
      that of two modifications tailored to children in predicting disease outcome.
      RESULTS: The longer the patient's median length of hospital stay was, the higher
      the adult and two proposed pediatric SCORTENs were. In addition, all patients who
      died had SCORTENs greater than 4. CONCLUSION: The pediatric-modified tools were
      not superior to the adult SCORTEN, which accurately predicted outcome.

PMID- 28508418
TI  - Quantitative analysis of cervical texture by ultrasound in mid-pregnancy and
      association with spontaneous preterm birth.
AB  - OBJECTIVE: New tools are required to improve the identification of women who are
      at increased risk for spontaneous preterm birth (sPTB). Quantitative analysis of
      tissue texture on ultrasound has been used to extract robust features from the
      ultrasound image to detect subtle changes in its microstructure. This may be
      applied to the cervix. The aim of this study was to determine if there is an
      association between quantitative analysis of cervical texture (CTx) on mid
      trimester ultrasound and sPTB < 37 + 0 weeks' gestation. METHODS: This was a
      single-center nested case-control study of a prospective cohort of 677
      consecutive women with singleton pregnancy assessed between 19 + 0 and 24 + 6
      weeks' gestation. Women at increased risk for sPTB were included unless they
      received treatment to prevent sPTB. Women who delivered < 37 + 0 weeks (sPTB)
      were considered as cases and were matched in a 1: 10 ratio with randomly selected
      contemporary controls who delivered at term. For each woman, one ultrasound image
      of the cervix was obtained for which quality was assessed, cervical length (CL)
      measured offline and a region of interest in the midportion of the anterior
      cervical lip delineated for use in local binary patterns analysis of CTx. A
      learning algorithm was developed to obtain the combination of CTx features best
      associated with sPTB based on feature transformation and discriminant analysis
      regression. The ability of the learning algorithm to predict sPTB was evaluated
      using a leave-one-out cross-validation technique, which produced a CTx-based
      score for each participant. Receiver-operating characteristics (ROC) curves were
      produced and sensitivity, specificity, and positive and negative likelihood
      ratios were calculated for the optimal cut-off based on the ROC curve. The
      results were compared with those obtained for CL. Investigators studying the
      images were blinded to pregnancy outcome at all times. RESULTS: Images from 310
      women (27 cases and 283 controls) were of sufficient quality and included in the
      study. Median CTx-based score was significantly lower in cases compared with
      controls (-1.01 vs -0.07, P <= 0.0001). CTx-based score maintained its
      significant association with sPTB after adjusting for possible confounders
      (history of sPTB, conization or Mullerian malformation, and CL < 25 mm). CTx
      based score was a better predictor of sPTB (AUC, 0.77; 95% CI, 0.66-0.87) than
      was CL (AUC, 0.60; 95% CI, 0.47-0.72) (P = 0.03). Median CL was similar for cases
      and controls (37.7 vs 38.6 mm, P = 0.26), although cases were more likely to have
      CL < 25 mm (18.5% vs 0.4%, P < 0.001). CONCLUSION: Quantitative analysis of CTx
      enables the extraction of information relevant to sPTB from ultrasound images to
      generate a CTx-based score that is associated independently with sPTB. Copyright
      (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28508420
TI  - Synthesis of beta-Lactams by Palladium(0)-Catalyzed C(sp3 )-H Carbamoylation.
AB  - A general and user-friendly synthesis of beta-lactams is reported that makes use
      of Pd0 -catalyzed carbamoylation of C(sp3 )-H bonds, and operates under
      stoichiometric carbon monoxide in a two-chamber reactor. This reaction is
      compatible with a range of primary, secondary and activated tertiary C-H bonds,
      in contrast to previous methods based on C(sp3 )-H activation. In addition, the
      feasibility of an enantioselective version using a chiral phosphonite ligand is
      demonstrated. Finally, this method can be employed to synthesize valuable
      enantiopure free beta-lactams and beta-amino acids.

PMID- 28508419
TI  - Case-control study shows that neonatal pneumococcal meningitis cannot be
      distinguished from group B Streptococcus cases.
AB  - AIM: Streptococcus pneumoniae (S. pneumoniae) is sometimes implicated in neonatal
      bacterial meningitis. This study described the demographic, clinical and
      biological features of neonatal S. pneumoniae meningitis and compared
      pneumococcal and group B streptococcal (GBS) neonatal meningitis. METHODS: We
      conducted a case-control study that compared neonates, aged one to 28 days with
      S. pneumoniae meningitis or GBS meningitis. Each case with S. pneumoniae was
      randomly matched to four control patients with GBS by age group and study year.
      RESULTS: From 2001 to 2013, the national French paediatric network, which
      comprises 227 paediatric wards, recorded 831 neonatal cases of meningitis. S.
      pneumoniae (n = 18, 2.2%) was the fifth infection cause after GBS (n = 464,
      55.8%), Escherichia coli (n = 232, 27.9%), Neisseria meningitidis (n = 23, 2.8%)
      and Listeria monocytogenes (n = 20, 2.4%). Neonatal pneumococcal and GBS
      meningitis did not differ in demographic data or clinical and biological
      characteristics. All S. pneumoniae strains were fully susceptible to cefotaxime,
      and we observed a decrease of 13-valent pneumococcal conjugate vaccine (PCV13)
      serotypes (88.9%-20.0%) after PCV13 implementation. CONCLUSION: Clinically and
      biologically, neonatal pneumococcal meningitis could not be distinguished from
      GBS cases. A herd effect of PCV13 implementation was suggested by the decrease in
      the prevalence of vaccine serotypes.

PMID- 28508422
TI  - Age-related inequalities in health and healthcare: the life stages approach.
AB  - How should healthcare systems prepare to care for growing numbers and proportions
      of older people? Older people generally suffer worse health than younger people
      do. Should societies take steps to reduce age-related health inequalities? Some
      express concern that doing so would increase age-related inequalities in
      healthcare. This paper addresses this debate by (1) presenting an argument in
      support of three principles for distributing scarce resources between age groups;
      (2) framing these principles of age group justice in terms of life stages; and
      (3) indicating policy implications that merit further attention in light of
      rapidly aging societies.

PMID- 28508421
TI  - Subversion of host kinases: a key network in cellular signaling hijacked by
      Helicobacter pylori CagA.
AB  - Helicobacter pylori is a paradigm of persistent pathogens and major risk factor
      for developing severe diseases including adenocarcinoma in the human stomach. An
      important bacterial factor linked to gastric disease progression is the cag
      pathogenicity island-encoded type-IV secretion system (T4SS) effector protein
      CagA. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-motifs and
      then activates or inactivates multiple host signaling proteins in a
      phosphorylation-dependent and phosphorylation-independent fashion. In this way,
      intracellular CagA acts as a 'masterkey' or 'picklock', which evolved during
      evolution to hijack key host cell signal transduction functions. Crucial targets
      of CagA represent a variety of serine/threonine and tyrosine kinases, which
      control major checkpoints of eukaryotic signaling. Here we review the signal
      transmission by translocated CagA on multiple receptor kinases (c-Met and EGFR)
      and non-receptor kinases (Src, Abl, Csk, aPKC, Par1, PI3K, Akt, FAK, GSK-3, JAK,
      PAK1, PAK2 and MAP kinases), manipulating a selection of fundamental processes in
      the human gastric epithelium such as cell adhesion, polarity, proliferation,
      motility, receptor endocytosis, cytoskeletal rearrangements, apoptosis,
      inflammation and cell cycle progression. This enormous complexity generates a
      highly remarkable and puzzling scenario during H. pylori infection. The
      contribution of these signaling pathways to bacterial survival, persistence and
      gastric pathogenesis is discussed.

PMID- 28508423
TI  - Oxoborane (RBO) Complexation and Concomitant Electrophilic Bond Activation
      Processes.
AB  - Donor-acceptor complexes of the oxoboranes ClB=O and HOB=O were synthesized and
      each feature short multiply bonded B=O linkages. The retention of high Lewis
      acidic character within these encapsulated monomeric oxoboranes was manifested by
      their ability to support C-F and Si-O bond activation/functionalization. The
      reported ClB=O complexes can be regarded as synthetic surrogates of the [BO]+
      cation, an inorganic analogue of CO.

PMID- 28508424
TI  - Computational site-directed mutagenesis studies of the role of the hydrophobic
      triad on substrate binding in cholesterol oxidase.
AB  - Cholesterol oxidase (ChOx) is a flavoenzyme that oxidizes and isomerizes
      cholesterol (CHL) to form cholest-4-en-3-one. Molecular docking and molecular
      dynamics simulations were conducted to predict the binding interactions of CHL in
      the active site. Several key interactions (E361-CHL, N485-FAD, and H447-CHL) were
      identified and which are likely to determine the correct positioning of CHL
      relative to flavin-adenine dinucleotide (FAD). Binding of CHL also induced
      changes in key residues of the active site leading to the closure of the oxygen
      channel. A group of residues, Y107, F444, and Y446, known as the hydrophobic
      triad, are believed to affect the binding of CHL in the active site.
      Computational site-directed mutagenesis of these residues revealed that their
      mutation affects the conformations of key residues in the active site, leading to
      non-optimal binding of CHL and to changes in the structure of the oxygen channel,
      all of which are likely to reduce the catalytic efficiency of ChOx. Proteins
      2017; 85:1645-1655. (c) 2017 Wiley Periodicals, Inc.

PMID- 28508425
TI  - Bimetallic Nickel-Substituted Cobalt-Borate Nanowire Array: An Earth-Abundant
      Water Oxidation Electrocatalyst with Superior Activity and Durability at Near
      Neutral pH.
AB  - There is an urgent demand to develop earth-abundant electrocatalysts for
      efficient and durable water oxidation under mild conditions. A nickel-substituted
      cobalt-borate nanowire array is developed on carbon cloth (Ni-Co-Bi/CC) via
      oxidative polarization of NiCo2 S4 nanoarray in potassium borate (K-Bi). As a
      bimetallic electrocatalyst for water oxidation, such Ni-Co-Bi/CC is superior in
      catalytic activity and durability in 0.1 m K-Bi (pH: 9.2), with a turnover
      frequency of 0.33 mol O2 s-1 at the overpotential of 500 mV and nearly 100%
      Faradaic efficiency. To drive a geometrical catalytic current density of 10 mA cm
      2 , it only needs overpotential of 388 mV, 34 mV less than that for Co-Bi/CC,
      outperforming reported non-noble-metal catalysts operating under benign
      conditions. Notably, its activity is maintained over 80 000 s. Density functional
      theory calculations suggest that the O* to OOH* conversion is the rate
      determining step and Ni substitution decreases the free energy on Co-Bi from
      2.092 to 1.986 eV.

PMID- 28508426
TI  - Role of transvaginal ultrasound in evaluation of ureteral involvement in deep
      infiltrating endometriosis.
AB  - OBJECTIVE: To assess whether routine examination of the ureters on transvaginal
      sonography (TVS) can identify reliably potential silent ureteral involvement by
      endometriosis and should therefore be recommended in all patients with deep
      infiltrating endometriosis (DIE). METHODS: This was a prospective study of 200
      consecutive patients scheduled for surgery for DIE, evaluated between January
      2012 and December 2014 at a tertiary endometriosis center at Fondazione
      Policlinico Universitario A. Gemelli, Rome, Italy. Routine TVS, abdominal
      ultrasound and gynecological examination were performed within 3 months before
      surgery, and patient history, signs and symptoms were recorded. Surgical and
      histological findings were compared with the preoperative ultrasonographic
      diagnosis. The main outcome of interest was the presence of ureteral dilatation
      or hydronephrosis caused by endometriosis. RESULTS: Of 200 patients with DIE,
      associated ureteral dilatation was diagnosed on TVS in 13 (6.5%) cases. Ureteral
      involvement was confirmed intraoperatively in all 13 cases by detection of
      ureteral dilatation caused by endometriotic tissue surrounding the ureter and
      causing stenosis. Of the 13 patients with ureteral dilatation, renal ultrasound
      detected six (46.2%) cases of hydronephrosis. Mean duration of visualization and
      study of dilated ureters was 5 min (range, 3-9 min). Ureteric diameter was >= 6
      mm in all cases of ureteral dilatation, with a median diameter of 6.9 mm (range,
      6-18 mm). Both ureters were identified on TVS in all 200 patients with DIE.
      CONCLUSIONS: Our study confirms a relatively high incidence of ureteral
      involvement in patients with DIE. TVS appears to be a reliable tool for the
      diagnosis of ureteral involvement and, additionally, it allows the detection of
      both the level and degree of obstruction. Our findings confirm that TVS
      examination is an accurate non-invasive diagnostic tool for the detection of
      ureteral involvement by endometriosis. Copyright (c) 2017 ISUOG. Published by
      John Wiley & Sons Ltd.

PMID- 28508428
TI  - Characterization and quantitation of PVP content in a silicone hydrogel contact
      lens produced by dual-phase polymerization processing.
AB  - Polyvinylpyrrolidone (PVP) has been incorporated over the years into numerous
      hydrogel contact lenses as both a primary matrix component and an internal
      wetting agent to increase lens wettability. In this study, complementary
      analytical techniques were used to characterize the PVP wetting agent component
      of senofilcon A and samfilcon A contact lenses, both in terms of chemical
      composition and amount present. Photo-differential scanning calorimetry (photo
      DSC), gas chromatography with a flame ionization detector (GC-FID), and high
      resolution/accurate mass (HR/AM) liquid chromatography-mass spectrometry (LC-MS)
      techniques confirmed dual phase reaction and curing of the samfilcon A silicone
      hydrogel material. Gel permeation chromatography (GPC) demonstrated that high
      molecular weight (HMW) polymer was present in isopropanol (IPA) extracts of both
      lenses. High-performance liquid chromatography (HPLC) effectively separated
      hydrophilic PVP from the hydrophobic silicone polymers present in the extracts.
      Collectively, atmospheric solids analysis probe mass spectrometry (ASAP MS),
      Fourier transform infrared (FTIR) spectroscopy, 1 H nuclear magnetic resonance
      (NMR) spectroscopy, GC-FID, and LC-MS analyses of the lens extracts indicated
      that the majority of NVP is consumed during the second reaction phase of
      samfilcon A lens polymerization and exists as HMW PVP, similar to the PVP present
      in senofilcon A. GC-FID analysis of pyrolyzed samfilcon A and senofilcon A
      indicates fourfold greater PVP in samfilcon A compared with senofilcon A. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1064
      1072, 2018.

PMID- 28508427
TI  - Evaluation of Benefit and Tolerability of IQP-CL-101 (Xanthofen) in the
      Symptomatic Improvement of Irritable Bowel Syndrome: A Double-Blinded,
      Randomised, Placebo-Controlled Clinical Trial.
AB  - Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown
      aetiology. There is currently no known cure, and pharmacological interventions
      are usually targeting symptomatic relief, where natural and herbal remedies also
      play a role. This study aimed to evaluate the benefit and tolerability of IQP-CL
      101 in symptomatic IBS relief. A double-blinded, randomised, placebo-controlled
      trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME-III
      criteria for IBS were randomised into two groups, given either two IQP-CL-101
      softgels or matching placebo twice daily before main meals. The primary endpoint
      was the difference in change of IBS Symptom Severity Score (IBS-SSS) after an 8
      week intake of IQP-CL-101 compared to placebo. After 8 weeks, subjects on IQP-CL
      101 showed a significant reduction in IBS-SSS (113.0 +/- 64.9-point reduction)
      compared to subjects on placebo (38.7 +/- 64.5-point reduction) (p < 0.001). A
      significant improvement could be seen as early as 4 weeks. No serious adverse
      events were reported throughout. IQP-CL-101 can be considered beneficial in the
      improvement of IBS symptom severity, regardless of IBS type, and therefore able
      to improve quality of life in patients suffering from abdominal pain and
      discomfort. (c) 2017 The Authors. Phytotherapy Research published by John Wiley &
      Sons Ltd.

PMID- 28508429
TI  - The cross talk between cervical carcinoma cells and vascular endothelial cells
      mediated by IL-27 restrains angiogenesis.
AB  - PROBLEM: To explore whether cervical carcinoma cell-derived interleukin-27 (IL
      27) modulates the angiogenesis of vascular endothelial cells. METHOD OF STUDY:
      The expression of IL-27 in cervical cancer tissues and cervical cell lines was
      analyzed by immunohistochemistry, ELISA and flow cytometry. Then, the effects of
      IL-27 on the proliferation and apoptosis-related molecules and angiogenesis in
      vitro of human umbilical vein endothelial cells (HUVECs) were investigated.
      Finally, in vivo experiment was performed to further confirm the effects of IL
      27. RESULTS: Compared with cervicitis, the cervical cancer tissues highly
      expressed IL-27. Both HeLa and CaSki cells secreted IL-27, and HUVECs expressed
      low levels of IL-27 receptors (IL-27R). However, the co-culture of cervical cell
      lines and HUVECs led to a significant elevation of IL-27R on HUVECs. Co-culturing
      with IL-27-overexpressed HeLa cells downregulated Ki-67 and Bcl-2 and upregulated
      Fas expression in HUVECs. In addition, overexpression of IL-27 in HeLa cells and
      CasKi cells secreted less IL-8 and could further restrict angiogenesis compared
      with control cells in vitro. In the subcutaneous tumorous model of C57/BL6 mouse,
      there were decreased vessel density and tumor volume when inoculation with IL-27
      overexpressed TC-1 cells. CONCLUSION: This study indicates that IL-27 secreted by
      cervical carcinoma cells restricts the angiogenesis in a paracrine manner in the
      pathogenesis of cervical cancer.

PMID- 28508430
TI  - Combined Delivery of a Lipopolysaccharide-Binding Peptide and the Heme Oxygenase
      1 Gene Using Deoxycholic Acid-Conjugated Polyethylenimine for the Treatment of
      Acute Lung Injury.
AB  - A ternary complex comprising plasmid DNA, lipopolysaccharide-binding peptide
      (LBP), and deoxycholic acid-conjugated polyethylenimine (PEI-DA) is prepared for
      combinational therapy of acute lung injury (ALI). The LBP is designed as an anti
      inflammatory peptide based on the lipopolysaccharide (LPS)-binding domain of HMGB
      1. In vitro cytokine assays show that LBP reduces levels of proinflammatory
      cytokines by inhibiting LPS. PEI-DA is synthesized as the gene carrier by
      conjugation of deoxycholic acid to low-molecular weight polyethylenimine (2 kDa,
      PEI2k). PEI-DA has higher transfection efficiency than high-molecular weight
      polyethylenimine (25 kDa, PEI25k). The ternary complex of an HO-1 plasmid (pHO
      1), PEI-DA, and LBP is prepared as a combinational system to deliver the
      therapeutic gene and peptide. The transfection efficiency of the ternary complex
      is higher than that of the pHO-1/PEI-DA binary complex. The ternary complex also
      reduces TNF-alpha secretion in LPS-activated Raw264.7 macrophage cells.
      Administration of the ternary complex into the lungs of an animal ALI model by
      intratracheal injection induces HO-1 expression and reduces levels of
      proinflammatory cytokines more efficiently than the pHO-1/PEI-DA binary complex
      or LBP alone. In addition, the ternary complex reduces inflammation in the lungs.
      Therefore, the pHO-1/PEI-DA/LBP ternary complex may be an effective treatment for
      ALI.

PMID- 28508431
TI  - A spatially balanced design with probability function proportional to the within
      sample distance.
AB  - The units observed in a biological, agricultural, and environmental survey are
      often randomly selected from a finite population whose main feature is to be geo
      referenced thus its spatial distribution should be used as essential information
      in designing the sample. In particular our interest is focused on probability
      samples that are well spread over the population in every dimension which in
      recent literature are defined as spatially balanced samples. To approach the
      problem we used the within sample distance as the summary index of the spatial
      distribution of a random selection criterion. Moreover numerical comparisons are
      made between the relative efficiency, measured with respect to the simple random
      sampling, of the suggested design and some other classical solutions as the
      Generalized Random Tessellation Stratified (GRTS) design used by the US
      Environmental Protection Agency (EPA) and other balanced or spatially balanced
      selection procedures as the Spatially Correlated Poisson Sampling (SCPS), the
      balanced sampling (CUBE), and the Local Pivotal method (LPM). These experiments
      on real and simulated data show that the design based on the within sample
      distance selects samples with a better spatial balance thus gives estimates with
      a lower sampling error than those obtained by using the other methods. The
      suggested method is very flexible to the introduction of stratification and
      coordination of samples and, even if in its nature it is computationally
      intensive, it is shown to be a suitable solution even when dealing with high
      sampling rates and large population frames where the main problem arises from the
      size of the distance matrix.

PMID- 28508432
TI  - Exploring Cryptic Diversity and Distribution Patterns in the Mallomonas
      kalinae/rasilis Species Complex with a Description of a New Taxon-Mallomonas
      furtiva sp. nov.
AB  - A complex of closely related Mallomonas taxa belonging to the section Papillosae,
      M. kalinae Rezacova and M. rasilis Durrschmidt, has been studied in detail by
      molecular and morphometric methods. Our investigations uncovered the existence of
      a new species found in water bodies in Vietnam, which we describe here as
      Mallomonas furtiva sp. nov. This taxon is morphologically very similar to M.
      kalinae, from which it differs by minute, but statistically significant
      morphological differences on the structure of silica scales. Indeed, the
      principal component analysis of morphological traits measured on silica scales
      significantly separates all three species in the complex. Mallomonas kalinae and
      M. furtiva differ by number of papillae on the shield and the dome, as well as by
      the scale sizes. Likewise, Mallomonas rasilis and M. furtiva are primarily
      differentiated by the absence of submarginal anterior ribs on silica scales of
      the former species. Phylogenetic analyses showed that Mallomonas furtiva is
      closely related to M. kalinae, with which it formed a highly supported lineage.
      Distribution patterns of all three studied taxa are further discussed.

PMID- 28508433
TI  - An investigation of the anti-inflammatory effects and a potential biomarker of
      PI3Kdelta inhibition in COPD T cells.
AB  - Lymphocyte numbers are increased in the lungs of chronic obstructive pulmonary
      disease (COPD) patients. Phosphatidylinositol-3-kinase delta (PI3Kdelta) is
      involved in lymphocyte activation. We investigated the effect of PI3Kdelta
      inhibition on cytokine release from COPD lymphocytes. We also evaluated
      phosphorylated ribosomal S6 protein (rS6) as a potential biomarker of PI3Kdelta
      activation. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage
      (BAL) cells isolated from healthy never smokers (HNS), smokers (S) and COPD
      patients were stimulated to induce a T cell receptor response. The effects of a
      PI3Kdelta specific inhibitor (GSK045) on cytokine release and rS6 phosphorylation
      were measured by Luminex and flow cytometry respectively. The effects of GSK045
      on cytokine production from PHA stimulated chopped lung samples were
      investigated. GSK045 reduced cytokine release from PBMCs, BAL cells and chopped
      lung. Inhibition was greatest in the chopped lung model, with approximately 80%
      inhibition of interferon (IFN) gamma, interleukin (IL)-2, IL-17 and IL-10.
      PI3Kdelta inhibition suppressed rS6 phosphorylation in unstimulated airway T
      lymphocytes by up to 60%. Inhibition of PI3Kdelta suppressed T cell cytokine
      production in COPD patients. rS6 phosphorylation shows potential as a biomarker
      to assess PI3Kdelta activity.

PMID- 28508434
TI  - Maternal arterial stiffness and fetal cardiovascular physiology in diabetic
      pregnancy.
AB  - OBJECTIVES: In mothers with pregestational or gestational diabetes, abnormal
      arterial stiffness (stiffer arteries) has been reported. The impact of abnormal
      maternal arterial stiffness on placental and fetal cardiovascular physiology is
      unknown. The purpose of this study was to determine the impact of maternal
      diabetes on maternal arterial stiffness and the association with fetal
      cardiovascular physiology as measured by fetal echocardiography. METHODS: Between
      December 2013 and January 2017 a prospective study was conducted on diabetic (but
      otherwise healthy) and non-diabetic, healthy pregnant mothers aged 18-40 years at
      20-28 weeks' gestation who had a normal fetal cardiac echocardiogram and
      obstetric ultrasound. Clinical data were collected by means of a patient
      questionnaire and measurement of blood pressure, height, weight, arterial
      augmentation index (AIx) and placental and fetal cardiovascular parameters were
      collected by fetal echocardiography. Descriptive statistics were calculated.
      Comparisons were made using parametric and non-parametric tests between controls
      and diabetic mothers. RESULTS: Twenty-three healthy pregnant controls and 43
      diabetic pregnant women (22 with pregestational and 21 with gestational diabetes)
      were included in the study. Maternal AIx was higher in those with diabetes than
      in healthy controls (12.4 +/- 10.6% vs 4.6 +/- 7.9%; P = 0.003). Fetal aortic
      valve (AoV) velocity time integral (VTI) was higher in fetuses whose mothers had
      diabetes than in those with non-diabetic mothers (7.7 +/- 1.9 cm vs 6.3 +/- 3.0
      cm; P = 0.022). Left ventricular (LV) myocardial performance index (MPI) was
      lower in diabetic pregnancies than in controls (0.40 +/- 0.09 vs 0.46 +/- 0.11; P
      = 0.021). Umbilical artery (UA) resistance index (RI) was lower in diabetic
      pregnancies with glycated hemoglobin (HbA1c) levels >= 6.5% than in those with
      HbA1c levels < 6.5% (0.69 +/- 0.06, n = 15 vs 0.76 +/- 0.08, n = 21; P = 0.009)
      but not at higher HbA1C cut-offs. No correlation between AIx and AoV-VTI, LV-MPI
      or UA-RI was found. CONCLUSIONS: Arterial stiffness is higher in pregnant women
      with diabetes than in controls. Fetuses of diabetic mothers show altered
      cardiovascular parameters, with higher AoV-VTI and lower LV-MPI, which are
      markers of myocardial function. Placental function assessed by UA-RI was normal
      despite differences between groups. Arterial stiffness did not correlate with
      placental or fetal cardiovascular variables. Instead, the findings are likely to
      represent a shared response to the environment of abnormal glucose metabolism.
      The clinical significance of these findings is yet to be determined. Copyright
      (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28508435
TI  - Graphene Oxide Conjugated Magnetic Beads for RNA Extraction.
AB  - A magnetic material that consists of silica-coated magnetic beads conjugated with
      graphene oxide (GO) was successfully prepared for facile ribonucleic acid (RNA)
      extraction. When the GO-modified magnetic beads were applied to separate the RNA
      from the lysed cell, the cellular RNAs were readily adsorbed to and readily
      desorbed from the surface of the GO-modified magnetic beads by urea. The amount
      of RNA extracted by the GO-modified magnetic beads was ~170 % as much as those of
      the control extracted by a conventional phenol-based chaotropic solution. These
      results demonstrate that the facile method of RNA separation by using GO-modified
      magnetic beads as an adsorbent is an efficient and simple way to purify intact
      cellular RNAs and/or microRNA from cell lysates.

PMID- 28508436
TI  - Bio-functional properties of sardine protein hydrolysates obtained by brewer's
      spent yeast and commercial proteases.
AB  - BACKGROUND: The canned-sardine industry generates large amounts of protein-rich
      waste, which demands useful exploitation. This paper describes the potential use
      of muscle and viscera proteins from canned sardine by-products as substrate to
      obtain hydrolysates with biological and functional properties. Three enzymatic
      approaches, brewer's spent yeast (Bsy) proteases, Alcalase(r) and Neutrase(r)
      were applied to perform protein hydrolysis at the same proteolytic activity (1 U
      mL-1 ), using an enzyme/substrate ratio of 20% (v/v), at 50 degrees C and for 7
      h. Hydrolysis degree (DH), antioxidant and angiotensin I-converting enzyme
      inhibitory (ACE-I) activities, functional properties (i.e. solubility,
      emulsifying and foaming properties, water and oil binding capacity) and colour
      were investigated. RESULTS: All hydrolysates presented a high protein content
      [52.7-83.2% dry weight (DW)] and low fat content (0.9-3.9% DW). Alcalase(r)
      treatment of muscle and viscera proteins resulted in higher DH (7.5% and 8.6%,
      respectively) and higher biological activities (P < 0.05). All hydrolysates had
      excellent solubility and presented functional properties. Among viscera
      hydrolysates, treatment with Bsy proteases promoted higher emulsion (80.1 m2 g-1
      ), foaming (79.2%) and oil binding capacity (5.8 g g-1 ) of viscera sardine
      proteins. CONCLUSION: Improved biological and functional properties were observed
      for sardine protein hydrolysates produced using the three enzymatic treatments
      tested. (c) 2017 Society of Chemical Industry.

PMID- 28508437
TI  - Characteristics and consequences of falls among older adult trauma patients:
      Considerations for injury prevention programs.
AB  - BACKGROUND/AIM: Health promotion and prevention is an important component of
      occupational therapy practice. Falls are one of the most common causes of ER
      visits among older adults and injurious falls requiring trauma care can have a
      significant impact on the health and quality of life of elders. The aim of this
      study was to compare characteristics and consequences of falls among older adult
      trauma patients across different age groups with an eye towards informing injury
      prevention programs. METHODS: A retrospective study using the trauma database
      from a level one trauma centre in the U.S. (N = 711) was conducted. We compared
      patient and fall characteristics across age groups and then used logistic
      regression to estimate odds ratios for hospital length of stay >4 days, discharge
      disposition, and injury severity (ISS >15). RESULTS: Associations between age
      group and fall height, location and alcohol use at the time of the fall were
      statistically significant (P < 0.0001). As compared to the reference group (85
      and older), younger age groups had lower odds ratios for discharge to a facility
      for rehabilitation. CONCLUSION: Results highlight differences among age groups of
      fallers admitted for trauma care and can help to inform injury prevention
      programs related to outdoor and indoor falls.

PMID- 28508438
TI  - The effect of chronotherapy on delirium in critical care - a systematic review.
AB  - BACKGROUND: Delirium is highly prevalent within critical care and is linked to
      adverse clinical outcomes, increased mortality and impaired quality of life.
      Development of delirium is thought to be caused by multiple risk factors,
      including disruption of the circadian rhythm. Chronotherapeutic interventions,
      such as light therapy, music and use of eye shades, have been suggested as an
      option to improve circadian rhythm within intensive care units. AIM: This review
      aims to answer the question: Can chronotherapy reduce the prevalence of delirium
      in adult patients in critical care? DESIGN: This study is a systematic review of
      quantitative studies. RESEARCH METHOD: Six major electronic databases were
      searched, and a hand search was undertaken using selected key search terms.
      Research quality was assessed using the critical appraisal skills programme
      tools. The studies were critically appraised by both authors independently, and
      data were extracted. Four themes addressing the research question were identified
      and critically evaluated. FINDINGS: Six primary research articles that
      investigated different methods of chronotherapy were identified, and the results
      suggest that multi-component non-pharmacological interventions are the most
      effective for reducing the prevalence of delirium in critical care. The
      melatonergic agonist Ramelteon demonstrated statistically significant reductions
      in delirium; however, the reliability of the results in answering the review
      question was limited by the research design. The use of bright light therapy
      (BLT) and dynamic light application had mixed results, with issues with the
      research design and outcomes measured limiting the validity of the findings.
      CONCLUSION: Multi-component non-pharmacological interventions, such as noise and
      light control, can reduce delirium in critical care, whereas other interventions,
      such as BLT, have mixed outcomes. Melatonin, as a drug, may be a useful
      alternative to sedative-hypnotics. RELEVANCE TO CLINICAL PRACTICE: Chronotherapy
      can reduce the incidence of delirium within critical care, although further
      research is warranted. Staff education is essential in the implementation of
      chronotherapy.

PMID- 28508439
TI  - Conventional and right-sided screening for subcutaneous ICD in a population with
      congenital heart disease at high risk of sudden cardiac death.
AB  - BACKGROUND: Information regarding suitability for subcutaneous defibrillator
      (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is
      scarce and needs to be further explored. The main objective of our study was to
      determine the proportion of patients with ToF and systemic right ventricle
      eligible for sICD with both, standard and right-sided screening methods.
      Secondary objectives were: (i) to study sICD eligibility specifically in patients
      at high risk of sudden cardiac death, (ii) to identify independent predictors for
      sICD eligibility, and (iii) to compare the proportion of eligible patients in a
      nonselected ICD population. METHODS: We recruited 102 patients with ToF, 33 with
      systemic right ventricle, and 40 consecutive nonselected patients. Conventional
      electrocardiographic screening was performed as usual. Right-sided alternative
      screening was studied by positioning the left-arm and right-arm electrodes 1 cm
      right lateral of the xiphoid midline. The Boston Scientific ECG screening tool
      was utilized. RESULTS: In high-risk patients with ToF, eligibility was higher
      with right-sided screening in comparison with standard screening (61% vs. 44%; p
      = .018). Eligibility in high-risk right ventricle population was identical with
      both screening methods (77%, p = ns). The only independent predictor for sICD
      eligibility was QRS duration. CONCLUSION: In high-risk patients with ToF, right
      sided implantation of the sICD could be an alternative to a conventional ICD. In
      patients with a systemic right ventricle, implantation of a sICD is an
      alternative to a conventional sICD.

PMID- 28508440
TI  - Has evidence-based medicine ever been modern? A Latour-inspired understanding of
      a changing EBM.
AB  - Evidence-based health care (EBHC), previously evidence-based medicine (EBM), is
      considered by many to have modernized health care and brought it from an
      authority-based past to a more rationalist, scientific grounding. But recent
      concerns and criticisms pose serious challenges and urge us to look at the
      fundamentals of a changing EBHC. In this paper, we present French philosopher
      Bruno Latour's vision on modernity as a framework to discuss current changes in
      the discourse on EBHC/EBM. Drawing on Latour's work, we argue that the early EBM
      movement had a strong modernist agenda with an aim to "purify" clinical reality
      into a dichotomy of objective "evidence" from nature and subjective "preferences"
      from human society and culture. However, we argue that this shift has proved
      impossible to achieve in reality. Several recent developments appear to point to
      a demise of purified evidence in the EBHC discourse and a growing recognition
      albeit implicit and undertheorized-that evidence in clinical decision making is
      relentlessly situated and contextual. The unique, individual patient, not
      abstracted truths from distant research studies, must be the starting point for
      clinical practice. It follows that the EBHC community needs to reconsider the
      assumption that science should be abstracted from culture and acknowledge that
      knowledge from human culture and nature both need translation and interpretation.
      The implications for clinical reasoning are far reaching. We offer some
      preliminary principles for conceptualizing EBHC as a "situated practice" rather
      than as a sequence of research-driven abstract decisions.

PMID- 28508441
TI  - Synthesis of an Aluminum Hydroxide Octamer through a Simple Dissolution Method.
AB  - Multimeric oxo-hydroxo Al clusters function as models for common mineral
      structures and reactions. Cluster research, however, is often slowed by a lack of
      methods to prepare clusters in pure form and in large amounts. Herein, we report
      a facile synthesis of the little known cluster Al8 (OH)14 (H2 O)18 (SO4 )5 (Al8 )
      through a simple dissolution method. We confirm its structure by single-crystal X
      ray diffraction and show by 27 Al NMR spectroscopy, electrospray-ionization mass
      spectrometry, and small- and wide-angle X-ray scattering that it also exists in
      solution. We speculate that Al8 may form in natural water systems through the
      dissolution of aluminum-containing minerals in acidic sulfate solutions, such as
      those that could result from acid rain or mine drainage. Additionally, the
      dissolution method produces a discrete Al cluster on a scale suitable for studies
      and applications in materials science.

PMID- 28508442
TI  - Solid-State Gas Adsorption Studies with Discrete Palladium(II) [Pd2 (L)4 ]4+
      Cages.
AB  - The need for effective CO2 capture systems remains high, and due to their
      tunability, metallosupramolecular architectures are an attractive option for gas
      sorption. While the use of extended metal organic frameworks for gas adsorption
      has been extensively explored, the exploitation of discrete metallocage
      architectures to bind gases remains in its infancy. Herein the solid state gas
      adsorption properties of a series of [Pd2 (L)4 ]4+ lantern shaped coordination
      cages (L = variants of 2,6-bis(pyridin-3-ylethynyl)pyridine), which had solvent
      accessible internal cavities suitable for gas binding, have been investigated.
      The cages showed little interaction with dinitrogen gas but were able to take up
      CO2 . The best performing cage reversibly sorbed 1.4 mol CO2 per mol cage at 298
      K, and 2.3 mol CO2 per mol cage at 258 K (1 bar). The enthalpy of binding was
      calculated to be 25-35 kJ mol-1 , across the number of equivalents bound, while
      DFT calculations on the CO2 binding in the cage gave DeltaE for the cage-CO2
      interaction of 23-28 kJ mol-1 , across the same range. DFT modelling suggested
      that the binding mode is a hydrogen bond between the carbonyl oxygen of CO2 and
      the internally directed hydrogen atoms of the cage.

PMID- 28508443
TI  - Stereoselective Synthesis of Tetrasubstituted Alkenes via a Cp*CoIII -Catalyzed C
      H Alkenylation/Directing Group Migration Sequence.
AB  - A highly atom economical and stereoselective synthesis of tetrasubstituted
      alpha,beta-unsaturated amides was achieved by a Cp*CoIII -catalyzed C-H
      alkenylation/directing group migration sequence. A carbamoyl directing group,
      which is typically removed after C-H functionalization, worked as an internal
      acylating agent and migrated onto the alkene moiety of the product. The directing
      group migration was realized with the Cp*CoIII catalyst, while a related Cp*RhIII
      catalyst did not promote the migration process. The product was further converted
      into two types of tricyclic compounds, one of which had fluorescent properties.

PMID- 28508444
TI  - Increased adipose tissue expression of IL-18R and its ligand IL-18 associates
      with inflammation and insulin resistance in obesity.
AB  - INTRODUCTION: The proinflammatory cytokine IL-18 is involved in the pathogenesis
      of metabolic syndrome. While the changes in IL-18 are known, IL-18R expression
      and relationship with IL-18 and other inflammatory markers in the adipose tissue
      in obesity/type-2 diabetes (T2D) remain unclear. METHODS: We, therefore,
      determined the adipose tissue expression of IL-18R and IL-18 mRNA/protein in
      lean, overweight, and obese individuals with and without T2D, 15 each, using qRT
      PCR, immunohistochemistry, and confocal microscopy. Data (mean +/- SEM) were
      analyzed using unpaired t-test and Pearson's correlation (r); all P values <=0.05
      were considered statistically significant. RESULTS: We found the upregulated
      gene/protein expression of IL-18R and IL-18 in non-diabetic obese/overweight as
      compared with lean individuals (P < 0.05). BMI correlated positively (P < 0.05)
      with the adipose tissue expression of IL-18R (mRNA: r = 0.90 protein: r = 0.84)
      and IL-18 (mRNA: r = 0.84 protein: r = 0.80). Similarly, in T2D individuals, gene
      and protein expression of IL-18R/IL-18 was significantly higher in obese as
      compared with overweight/lean individuals. The BMI was associated with the
      changes in both IL-18R (mRNA: r = 0.55 protein: r = 0.50) and IL-18 (mRNA: r =
      0.53 protein: r = 0.57) expression. IL-18R/IL-18 gene expression in the adipose
      tissue was positively associated (P < 0.05) with local gene expression of other
      inflammatory markers including CD11c, CD86, CD68, CD163, TNF-alpha, and CCL5.
      Homeostatic model assessment of insulin resistance (HOMA-IR) was higher in
      diabetic/non-diabetic obese and it correlated with BMI (P < 0.05). IL-18R and IL
      18 mRNA/protein expression in obesity was associated with HOMA-IR only in non
      diabetics. CONCLUSIONS: The adipose tissue IL-18R/IL-18 expression is enhanced in
      obesity which associates with proinflammatory gene signature and insulin
      resistance in these individuals.

PMID- 28508445
TI  - Adult height and glucose tolerance: a re-appraisal of the importance of body mass
      index.
AB  - AIM: To study both the association between adult height and glucose regulation
      based on findings from a 75-g oral glucose tolerance test, and the combined
      effect of height and adiposity on glucose values. METHODS: We conducted a
      population-based, cross-sectional study among apparently healthy people with high
      cardiovascular risk living in south-western Finland. The study included 2659
      participants aged 45-70 years, who had at least one cardiovascular risk factor
      but no previously diagnosed diabetes or manifested cardiovascular disease. An
      oral glucose tolerance test was performed in all participants. Height and weight
      were measured and BMI was calculated. The participants were divided into five
      height groups based on normal distribution. For further analysis of the
      association between height and glucose concentrations the participants were
      divided into four BMI groups (<25.0 kg/m2 ; 25-29.9 kg/m2 ; 30-34.9 kg/m2 ; >=35
      kg/m2 ). Data were analysed using age-adjusted linear regression models. RESULTS:
      Height was inversely associated with 2-h plasma glucose, but not with fasting
      plasma glucose concentration. No gender difference was observed. The 2-h plasma
      glucose values increased with an increase in BMI, so that height was inversely
      associated with 2-h plasma glucose in the three lowest BMI groups, but not in the
      highest BMI group (P=0.33). CONCLUSIONS: Taller people had lower 2-h plasma
      glucose concentrations than shorter people, up to a BMI of 35 kg/m2 . Adjustment
      for height and BMI is needed for accurate interpretation of oral glucose
      tolerance tests.

PMID- 28508446
TI  - Triboluminescence of Lanthanide Coordination Polymers with Face-to-Face Arranged
      Substituents.
AB  - Luminescence upon the grinding of solid materials (triboluminescence, TL) has
      long been a puzzling phenomenon in natural science and has also attracted
      attention because of its broad application in optics. It has been generally
      considered that the TL spectra exhibit similar profiles as those of
      photoluminescence (PL), although they occur from distinct stimuli. Herein, we
      describe for the first time a large spectral difference between these two
      physical phenomena using lanthanideIII coordination polymers with efficient TL
      and PL properties. They are composed of emission centers (TbIII and EuIII ions),
      antenna (hexafluoroacetylacetonate=hfa), and bridging ligands (2,5
      bis(diphenylphosphoryl)furan=dpf). The emission color upon grinding (yellow TL)
      is clearly different from that upon UV irradiation (reddish-orange PL) in TbIII
      /EuIII -mixed coordination polymers [Tb,Eu(hfa)3 (dpf)]n (Tb/Eu=1). The results
      directly indicate the discrete excitation processes of PL and TL.

PMID- 28508447
TI  - The gut-brain connection and the use of probiotics for the treatment of
      depression, anxiety and obsessive-compulsive disorders in dermatology.

PMID- 28508448
TI  - A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma
      immunotherapy.
AB  - The identification of novel tumour-associated antigens is urgently needed to
      improve the efficacy of immunotherapy for multiple myeloma (MM). In this study,
      we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that
      was specifically expressed in MM and exhibited significantly positive correlation
      with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested
      their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine
      was shown to induce an obvious CTL response in vitro. To improve the
      immunotherapy, we constructed a multi-epitope peptide vaccine by combining
      epitopes derived from MMSA-1 and Dickkopf-1 (DKK1). The effector T cells induced
      by multi-epitope peptide vaccine-loaded dendritic cells lysed U266 cells more
      effectively than MMSA-1/DKK1 single-epitope vaccine. In myeloma-bearing severe
      combined immunodeficient mice, the multi-epitope vaccine improved the survival
      rate significantly compared with single-epitope vaccine. Consistently, multi
      epitope vaccine decreased the tumour volume greatly and alleviated bone
      destruction. The frequencies of CD4+ and CD8+ T cells was significantly increased
      in mouse blood induced by the multi-epitope vaccine, indicating that it inhibits
      myeloma growth by changing T cell subsets and alleviating immune paralysis. This
      study identified a novel peptide from MMSA-1 and the multi-epitope vaccine will
      be used to establish appropriate individualized therapy for MM.

PMID- 28508449
TI  - Satellite glial cells in human trigeminal ganglia have a broad expression of
      functional Toll-like receptors.
AB  - Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of
      danger- and pathogen-associated molecular patterns. Compared to the central
      nervous system (CNS), expression profile and function of TLRs in the human
      peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of
      satellite glial cells (SGCs) and microglia, glial cells predominantly involved in
      local immune responses in ganglia of the human PNS and normal-appearing white
      matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell
      suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed
      that both SGCs and microglia expressed TLR1-5, TLR7, and TLR9, although
      expression levels varied between these cell types. Immunohistochemistry confirmed
      expression of TLR1-TLR4 and TLR9 by SGCs in situ. Stimulation of TG- and NAWM
      derived cell suspensions with ligands of TLR1-TLR6, but not TLR7 and TLR9,
      induced interleukin 6 (IL-6) secretion. We identified CD45LOW CD14POS SGCs and
      microglia, but not CD45HIGH leukocytes and CD45NEG cells as the main source of IL
      6 and TNF-alpha upon stimulation with TLR3 and TLR5 ligands. In conclusion, human
      TG-resident SGCs express a broad panel of functional TLRs, suggesting their role
      in initiating and orchestrating inflammation to pathogens in human sensory
      ganglia.

PMID- 28508450
TI  - Simultaneous assessment of both lung morphometry and gas exchange function within
      a single breath-hold by hyperpolarized 129 Xe MRI.
AB  - During the measurement of hyperpolarized 129 Xe magnetic resonance imaging (MRI),
      the diffusion-weighted imaging (DWI) technique provides valuable information for
      the assessment of lung morphometry at the alveolar level, whereas the chemical
      shift saturation recovery (CSSR) technique can evaluate the gas exchange function
      of the lungs. To date, the two techniques have only been performed during
      separate breaths. However, the request for multiple breaths increases the cost
      and scanning time, limiting clinical application. Moreover, acquisition during
      separate breath-holds will increase the measurement error, because of the
      inconsistent physiological status of the lungs. Here, we present a new method,
      referred to as diffusion-weighted chemical shift saturation recovery (DWCSSR), in
      order to perform both DWI and CSSR within a single breath-hold. Compared with
      sequential single-breath schemes (namely the 'CSSR + DWI' scheme and the 'DWI +
      CSSR' scheme), the DWCSSR scheme is able to significantly shorten the breath-hold
      time, as well as to obtain high signal-to-noise ratio (SNR) signals in both DWI
      and CSSR data. This scheme enables comprehensive information on lung morphometry
      and function to be obtained within a single breath-hold. In vivo experimental
      results demonstrate that DWCSSR has great potential for the evaluation and
      diagnosis of pulmonary diseases.

PMID- 28508451
TI  - Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome
      in Patients With Pulmonary Arterial Hypertension.
AB  - Diastolic dysfunction may influence perioperative outcome, early graft function,
      and long-term survival. We compared the outcomes of double lung transplantation
      (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative
      left ventricular (LV) diastolic dysfunction with the outcomes of patients without
      diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent
      transplantation between January 1995 and December 2013), 44 met our inclusion and
      exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction
      pretransplantation had a higher body mass index (29 [IQR 21.5-32.6] vs 22.4 [IQR
      19.9-25.3] kg/m2 ) and mean pulmonary arterial pressure (54.6 +/- 10 mmHg vs 47
      +/- 11.3 mmHg) and right atrial pressure (16.5 +/- 5.2 mmHg vs 10.6 +/- 5.2
      mmHg). The patients received extracorporeal life support more frequently (33% vs
      7% [p = 0.02]), had worse APACHE II scores (21.7 +/- 7.4 vs 15.3 +/- 5.3 [p =
      0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5-32.5] vs 17
      [IQR 3-23] [p = 0.08]). There was no effect on development of primary graft
      dysfunction or intensive care unit/hospital survival. One-year survival was worse
      (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3-22, p = 0.02).
      Diastolic dysfunction was the only variable that correlated with overall survival
      (HR 5.4, 95% CI 1.3-22, p = 0.02). Diastolic dysfunction leads to early
      postoperative morbidity and worse survival in patients with PAH after DLTx.

PMID- 28508452
TI  - Mental health cost of terrorism: Study of the Charlie Hebdo attack in Paris.
AB  - This study examines whether a terrorist attack in a developed country, which does
      not cause major damage to its capital stocks, affects the mental health of its
      residents. By exploiting variations in survey dates of the European Social
      Survey, we use a difference-in-differences strategy to show that the attack
      adversely affects subjective well-being and mental health measures of French
      respondents. These negative effects are stronger for immigrants and low-income
      individuals. The impact is less dramatic for politically extreme right-wing
      supporters. The distance from origin has little impact on these measures.

PMID- 28508453
TI  - TetR-dependent gene regulation in intracellular Listeria monocytogenes
      demonstrates the spatiotemporal surface distribution of ActA.
AB  - To enable specific and tightly controlled gene expression both in vitro and
      during the intracellular lifecycle of the pathogen Listeria monocytogenes, a TetR
      dependent genetic induction system was developed. Highest concentration of
      cytoplasmic TetR and best repression of tetO-controlled genes was obtained by
      tetR expression from the synthetic promoter Pt17 . Anhydrotetracycline (ATc) as
      inducer permitted concentration-dependent, fine-tuned expression of genes under
      control of the tetO operator and a suitable promoter. The actin-polymerizing ActA
      protein represents a major virulence factor of L. monocytogenes, required for
      actin-based motility and cell-to-cell spread in infected host cells. To be able
      to observe its spatial and temporal distribution on intracellular L.
      monocytogenes cells, conditional mutants featuring actA placed under TetR control
      were used to infect PtK2 epithelial cells. Following induction at different time
      intervals, the subsequent recruitment of actin by L. monocytogenes could be
      monitored. We found that cells displayed functional ActA after approximately 15
      min, while formation of polarized actin tail was complete after 90-120 min. At
      this point, intracellular motility of the induced mutants was indistinguishable
      from wild-type bacteria. Interestingly, de novo ActA synthesis in intracellular
      Listeria also demonstrated the temporal, asymmetric redistribution of the
      membrane-anchored proteins from the lateral walls toward the cell poles.

PMID- 28508454
TI  - Light-Mediated Reversible Modulation of ROS Level in Living Cells by Using an
      Activity-Controllable Nanozyme.
AB  - Nanozymes have shown great potential in bioapplications owing to their low cost,
      high stability, multiple activity, and biocompatibility. However, most of the
      known nanozymes are always at turn-on state, hindering their further
      applications. Herein, a simple and versatile method for constructing activity
      controllable nanozymes is presented. To the best of our knowledge, this is the
      first report to utilize the light-driven isomerization of azobenzene (Azo) and
      host-guest interaction to reversibly photoregulating the activity of nanozyme.
      Gold nanoparticles as a typical catalase-mimic nanozyme are used in this design.
      The expanded Azo-modified mesoporous silica is employed as supported material to
      encapsulate and disperse Au nanoparticles, which further combines with
      cyclodextrin (CD). The catalytic activity of the nanozyme is blocked by CD and
      can be activated or inhibited reversibly by UV or visible light. The results
      indicated that the nanozyme can reversibly regulate reactive oxygen species (ROS)
      level in extracellular and intracellular environment for multiple cycles and
      change cell viability by simply changing the irradiated light. This is a general
      method and can be adapted to construct various smart nanozymes with highly
      spatiotemporal resolution.

PMID- 28508455
TI  - A multicenter real-life study of the efficacy of an alpha-blocker with or without
      anticholinergic agent (imidafenacin) treatment in patients with lower urinary
      tract symptoms/benign prostatic hyperplasia and storage symptoms.
AB  - AIMS: To evaluate the efficacy and safety of combination therapy comprising a
      short-acting anticholinergic, imidafenacin and an alpha-blocker compared with
      monotherapy with an alpha-blocker only in men with lower urinary tract symptoms
      (LUTS) and storage symptoms. METHODS: The 12-week, prospective, double-blind,
      randomised trial enrolled men with LUTS and storage symptom. The inclusion
      criteria were a total International Prostate Symptom Score (IPSS) >=12, an IPSS
      question 4 score >=2, >=8 micturitions in 24 hours, and a prostate volume >20 mL.
      The primary outcome was a change in the micturition number from baseline. Bladder
      diary variables, Patient Perception of Intensity of Urgency Scale (PPIUS) scores,
      IPSS and safety were assessed. RESULTS: Of 260 patients screened, 221 completed
      the study. Patients were randomly assigned to receive an alpha-blocker only
      (n=111, group 1) or combination therapy comprising an alpha-blocker and an
      anticholinergic (n=110, group 2) for 12 weeks. Group 1 and 2 showed significant
      improvement in their 24-hour micturition numbers (-1.87 and -2.08, respectively),
      nocturia episodes (-0.48 and -0.53, respectively), total IPSS (-9.9 and -8.8,
      respectively), and PPIUS scores (-0.19 and -0.24, respectively). Micturition
      number per 24 hours, daytime frequency, urgency, the PPIUS score, the IPSS
      question 4 score and IPSS QoL score improved significantly in the combination
      therapy group, but changes in total IPSS, nocturia episodes, and safety outcomes
      did not differ significantly between the groups. CONCLUSIONS AND CLINICAL
      IMPLICATIONS: Compared with treatment with an alpha-blocker alone, combination
      therapy comprising an anticholinergic and an alpha-blocker showed superior
      efficacy and its safety was similar in patients with LUTS and storage symptoms.

PMID- 28508456
TI  - Age- and sex-based reference ranges for non-invasive ventricular repolarisation
      parameters.
AB  - BACKGROUND: Some electrocardiographic parameters are able to assess indirectly
      ventricular repolarisation homogeneity. It is consequently essential to
      discriminate between normal and abnormal values in clinical decision-making.
      Considering there is still not a consensus about normal cut-off values, the aim
      of this study was to document reference intervals in all age groups of a healthy
      population, providing for age- and sex-percentile tables, which can be used
      easily and quickly in clinical practice. METHODS: We evaluated repolarisation
      markers in 606 sex-matched participants aged 1 day-94 years. Each subject
      underwent a 12-lead electrocardiogram at rest, and the following parameters were
      measured: QT, corrected QT, QTpeak, Tpeak-Tend, Tpeak-Tend dispersion, Tpeak
      Tend/QT and QTpeak/QT ratio. RESULTS: A relationship was demonstrated between age
      and QTpeak, Tpeak-Tend, QT and QTc. In children, QTpeak, Tpeak-Tend and QT
      intervals increased linearly with age. In adolescents, all the three parameters
      remained stable. In adults, QTpeak and QT showed a further significant increase.
      On the contrary, Tpeak-Tend interval was longer in adults aged between 20 and 64
      years than in participants aged 65 years or over, but the difference was not
      statistically significant. Male vs female participants showed longer Tpeak-Tend
      intervals; this sex difference was not statistically significant at birth and
      during childhood, whereas it was in adolescents and in adults. CONCLUSIONS:
      Repolarisation parameters showed age- and sex-based variations, which are
      important to know to differentiate normal from pathological values.

PMID- 28508458
TI  - Required reading to remain relevant.

PMID- 28508457
TI  - Effects of canagliflozin on cardiovascular risk factors in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND AND AIMS: Cardiovascular disease is the most common cause of morbidity
      and mortality among people with type 2 diabetes mellitus (T2DM). The main
      contributors to cardiovascular risk in T2DM are chronic hyperglycaemia, reduced
      insulin sensitivity, hypertension and dyslipidaemia. Other cardiovascular risk
      factors include obesity and visceral adiposity, increased arterial stiffness and
      renal dysfunction. Results from clinical trials, including a long-term
      cardiovascular outcome study, have shown that sodium glucose co-transporter 2
      (SGLT2) inhibitors can provide multiple cardiometabolic benefits beyond glycaemic
      control including inducing mild osmotic diuresis, natriuresis and weight loss.
      This review article describes the effects of canagliflozin on cardiovascular risk
      factors based on results from its clinical development programme. METHODS: This
      review is based on structured searches to identify literature related to the
      effects of canagliflozin on cardiovascular risk factors in patients with T2DM.
      DISCUSSION AND CONCLUSIONS: Canagliflozin treatment has been shown to provide
      glycaemic improvements as well as reductions in blood pressure and body weight
      across a broad range of patients with T2DM, including those with elevated
      cardiovascular risk. Other observed effects of canagliflozin that may contribute
      to improved cardiometabolic outcomes include reduction in uric acid levels,
      decreased albuminuria and increases in serum magnesium. Results of ongoing long
      term cardiovascular outcomes studies of canagliflozin are expected to provide
      additional evidence on the cardiometabolic effects of canagliflozin treatment.

PMID- 28508459
TI  - Tailoring pharmacotherapy for male lower urinary tract symptoms: A prospective,
      multicenter, observational trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the pattern of tailoring and
      efficacy of several types of pharmacotherapy in male LUTS. METHODS: Prospectively
      404 male subjects were included who were over 40 years old, had at least 3 months
      symptom duration, and 12 or higher international prostate symptom score (IPSS).
      Subjects were treated with several types of pharmacotherapy for 6 months and were
      evaluated with IPSS/QoL at every follow-up. Subjects were subdivided into storage
      (44%), nocturia (18.5%), and voiding symptom (37.5%) groups according to the most
      bothersome symptom. RESULTS: At 6 months, 188 subjects (46.5%) completed the
      study. The mean age was 64.2+/-8.5 years, and symptom duration was 30.6+/-32.6
      months. PSA was 2.98+/-7.96 ng/mL, and prostate size was 32.8+/-14.2 cc. IPSS
      continually decreased from baseline (18.7) to last follow-up (10.8). Combination
      therapy increased from 33.0% to 52.7% at last follow-up (P=.006). However, there
      was no difference of IPSS changes between combination and monotherapy groups
      (P>.05). Only antimuscarinic prescription significantly increased from 15.4% to
      28.2% (P=.004). Mean number of visits to the clinic was 3.6+/-1.3 and the number
      of treatment changes was 0.31+/-0.47. The nocturia (0.47+/-0.51) group changed
      treatment more than voiding group (0.21+/-0.41, P=.003). However, the voiding
      group (-9.4) had significantly more improvement than e storage (-6.4) and
      nocturia (-7.8) groups (P=.011). CONCLUSIONS: Male LUTS continually improved over
      6 months with customised treatment. Pharmacotherapy for male LUTS should be
      tailored by symptom type and alteration of symptoms during treatment.

PMID- 28508460
TI  - Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany
      and the UK: A retrospective and prospective observational study (MELABIS).
AB  - AIM: Real-world data on treatment patterns/outcomes in patients with advanced
      melanoma, while scarce, are useful for health technology assessments that govern
      patient access in many countries. We collected retrospective data on treatment
      patterns among patients in France, Germany and the UK with Stage IIIB/IIIC
      melanoma with macroscopic lymph node involvement, whose primary melanoma and
      regional lymph node metastases had been completely resected. METHODS: Patients
      >=18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were
      obtained from patients' medical records and a patient survey. RESULTS: Forty-nine
      centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were
      of working age (<65 years), 22.5% reported a change in employment status due to
      melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study
      period. Overall median distant metastases-free survival was 23.4 months and
      median disease-free survival was 13.3 months. Hospitalisation frequency increased
      during distant metastatic/terminal disease phases. Adjuvant therapy was received
      by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5%
      (55/164) in Germany. Low-dose interferon was used more frequently than other
      regimens. High-dose interferon was associated with discontinuation in 28.6% and
      dose delay/reduction in 33.3% of patients. CONCLUSIONS: Rapid disease progression
      combined with increased use of healthcare resources in later phases of disease
      result in a high burden-of-illness for patients and healthcare providers. The use
      of adjuvant interferon therapy varies considerably in this population in the
      countries studied, highlighting the need for improved treatments for melanoma.

PMID- 28508461
TI  - FOXP3 polymorphisms in interstitial lung disease among Chinese Han population: A
      genetic association study.
AB  - INTRODUCTION: Both genetic and environmental factors are implicated in the
      pathogenesis of interstitial lung disease (ILD). Single-nucleotide polymorphisms
      (SNPs) in FOXP3 genes were implicated in the causation of some autoimmune
      diseases; however, association of these genes and ILD has not been reported.
      OBJECTIVES: To investigate whether FOXP3 polymorphisms are associated with ILD in
      a representative Chinese population. METHODS: One hundred and fifty-seven ILD
      patients and 170 healthy controls were recruited; SNPs were genotyped by the
      Sequenom MassARRAY platform and SHEsis was used to estimate the haplotype
      frequencies of SNPs. RESULTS: The CC and TC genotypes of FOXP3 rs2280883 were
      associated with a significantly higher risk of connective tissue disease
      associated ILD (CTP-ILD) than the TT genotype (P = .006). Patients with
      idiopathic interstitial pneumonia (IIP) showed a significantly higher frequency
      of rs3761547 (GG genotype) and rs3761549 (CC genotype) polymorphisms of FOXP3 as
      compared to that in controls (P = .038 and P = .026, respectively). The rs2294021
      (TC genotype) was less frequently observed among IIP patients as compared to that
      in controls (P = 0.029). In addition, the FOXP3 CAATC haplotype was associated
      with a greater risk for CTD-ILD (P =.048) as compared to controls, and the FOXP3
      TCCCC haplotype showed an increased IIP risk (P = .001); however, patients with
      the FOXP3 TACTT haplotype showed a significant protective effect against IIP (P =
      .036). CONCLUSION: FOXP3 polymorphisms may be important markers to determine
      susceptibility to IIP or CTP-ILD in Chinese population.

PMID- 28508462
TI  - Role of diffusion-weighted imaging in distinguishing thoracoabdominal
      neuroblastic tumours of various histological types and differentiation grades.
AB  - INTRODUCTION: Diffusion-weighted MR imaging (DWI) has demonstrated a great
      potential to help distinguish benign from malignant tumours in paediatric body.
      Our purpose is to evaluate whether DWI allow discrimination of thoracoabdominal
      neuroblastic tumours of various histological types and differentiation grades.
      METHODS: We retrospectively analysed DWI scans of the thoracoabdominal
      neuroblastic tumours in 25 children (11 girls, 14 boys). DWI was performed with
      two b-values of 0 and 800 s/mm2 on a 3.0T MR scanner. The apparent diffusion
      coefficient (ADC) values of different classifications of tumours were compared
      with Independent-Samples T Test. RESULTS: In the 25 cases, ganglioneuroma (GN)
      was in 3 cases, ganglioneuroblastoma (GNB) in 7 (GNB-Intermixed in 4, GNB-Nodular
      in 3) and neuroblastoma (NB) in 15. In three cases of GNB-Nodular, two cases had
      poorly differentiated nodules and another had differentiated nodules. In 15 cases
      of NB, poorly differentiated, differentiated and undifferentiated tumours were,
      respectively, in eight, five and two cases. The ADC value of the NB was
      significantly lower than that of GN/GNB (P < 0.001). The ADC of GNB-Nodular/NB
      was significantly less than that of GN/GNB-Intermixed (P < 0.0001). In GNB
      Nodular/NB detection, there was a cut-off value of 1.165 * 10-3  mm2 /s. In GNB
      Nodular/NB, the tumours with poorly differentiated and undifferentiated lesions
      (n = 12) had significantly smaller ADC than those with differentiated composition
      (n = 6) (P = 0.0012). CONCLUSION: ADC of DWI is highly valuable for
      discriminating thoracoabdominal neuroblastic tumours of different histological
      types and differentiation grades.

PMID- 28508463
TI  - Ovarian high-grade endometrioid stromal sarcoma with YWHAE and NUTM2B
      rearrangements.

PMID- 28508464
TI  - Arsenic-Rich Polyarsenides Stabilized by Cp*Fe Fragments.
AB  - The redox chemistry of [Cp*Fe(eta5 -As5 )] (1, Cp*=eta5 -C5 Me5 ) has been
      investigated by cyclic voltammetry, revealing a redox behavior similar to that of
      its lighter congener [Cp*Fe(eta5 -P5 )]. However, the subsequent chemical
      reduction of 1 by KH led to the formation of a mixture of novel Asn scaffolds
      with n up to 18 that are stabilized only by [Cp*Fe] fragments. These include the
      arsenic-poor triple-decker complex [K(dme)2 ][{Cp*Fe(MU,eta2:2 -As2 )}2 ] (2) and
      the arsenic-rich complexes [K(dme)3 ]2 [(Cp*Fe)2 (MU,eta4:4 -As10 )] (3),
      [K(dme)2 ]2 [(Cp*Fe)2 (MU,eta2:2:2:2 -As14 )] (4), and [K(dme)3 ]2 [(Cp*Fe)4 (MU4
      ,eta4:3:3:2:2:1:1 -As18 )] (5). Compound 4 and the polyarsenide complex 5 are the
      largest anionic Asn ligand complexes reported thus far. Complexes 2-5 were
      characterized by single-crystal X-ray diffraction, 1 H NMR spectroscopy, EPR
      spectroscopy (2), and mass spectrometry. Furthermore, DFT calculations showed
      that the intermediate [Cp*Fe(eta5 -As5 )]- , which is presumably formed first,
      undergoes fast dimerization to the dianion [(Cp*Fe)2 (MU,eta4:4 -As10 )]2- .

PMID- 28508466
TI  - Comparison of the time taken for localised breast surgery pre- and post
      introduction of intra-operative digital specimen mammography.
AB  - INTRODUCTION: More than half of the patients with an impalpable malignant breast
      lesion have a mammographically detected and imaged-guided localisation, which can
      be technically challenging for the breast surgeon. Specimen imaging is used to
      confirm successful excision of the localised index lesion and has improved the
      operating list efficiency resulting in a higher number of excisions per surgical
      list. The aim of this study was to evaluate whether introducing IDSM (intra
      operative digital specimen mammography) saved operation time for localised breast
      surgery. METHODS: A single-centre retrospective review was undertaken to compare
      the operation time (from incision to wound closure) taken for excision of 114
      consecutive image-guided localised impalpable breast lesions, performed using
      departmental specimen radiography (DSR), 6 months prior to the introduction of
      IDSM (Hologic, Trident(r) ) in March 2013, with the theatre time taken for
      excision of 121 consecutive image-guided localised impalpable breast lesions in
      the 6 months following introduction of IDSM. RESULTS: There was no significant
      difference in mean surgical time, which were 47.8 (+/-27.3) minutes in the CSR
      group and 48.8 (+/-25.7) minutes in the IDSM group. CONCLUSION: We were expecting
      to confirm a reduction in theatre time with the introduction of IDSM.
      Surprisingly, no difference in operating times was demonstrated. Factors that
      influenced the impact of IDSM included the proximity of the imaging department to
      the operating theatre.

PMID- 28508467
TI  - Keratitis due to microfilariae in dogs: a newly recognized disease.
AB  - Parasitic agents have been associated with keratitis, but a diagnosis of
      parasitic keratitis has not been commonly made in domestic animals. The purpose
      of this study was to describe the clinical and histopathological findings in
      seven dogs with chronic keratitis caused by microfilariae diagnosed in Brazil.
      All dogs presented with superficial corneal opacities of varying degrees
      affecting the perilimbal and central regions of the cornea, with other opaque
      areas appearing as crystalline deposits and corneal vascularization. The lesions
      were bilateral and were associated with mild-to-moderate conjunctival hyperemia.
      There was no history of blepharospasm or pruritus, and no subjects presented with
      epithelial erosions. Corneal biopsy revealed free microfilariae in the corneal
      stroma, with varying degrees of inflammation and collagen fiber destruction. The
      microfilariae were also found in skin lesions by skin snip technique. No adult
      worms were found in these dogs, and no dogs were on heartworm preventative before
      diagnosis. Monthly doses of oral ivermectin improved ocular and dermal lesions.
      One dog showed complete remission with the treatment. The species of the
      microfilariae was not identified.

PMID- 28508465
TI  - Proteomics show antigen presentation processes in human immune cells after AS03
      H5N1 vaccination.
AB  - Adjuvants enhance immunity elicited by vaccines through mechanisms that are
      poorly understood. Using a systems biology approach, we investigated temporal
      protein expression changes in five primary human immune cell populations:
      neutrophils, monocytes, natural killer cells, T cells, and B cells after
      administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split
      virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential
      signal between vaccine groups. On day 3 post-vaccination, several antigen
      presentation-related pathways, including MHC class I-mediated antigen processing
      and presentation, were enriched in monocytes and neutrophils and expression of
      HLA class I proteins was increased in the Adjuvant System 03 group. We identified
      several protein families whose proteomic responses predicted seroprotective
      antibody responses (>1:40 hemagglutination inhibition titer), including
      inflammation and oxidative stress proteins at day 1 as well as immunoproteasome
      subunit (PSME1 and PSME2) and HLA class I proteins at day 3 in monocytes. While
      comparison between temporal proteomic and transcriptomic results showed little
      overlap overall, enrichment of the MHC class I antigen processing and
      presentation pathway in monocytes and neutrophils was confirmed by both
      approaches.

PMID- 28508468
TI  - Photocatalytic Self-Doped SnO2-x Nanocrystals Drive Visible-Light-Responsive
      Color Switching.
AB  - Visible-light-responsive reversible color-switching systems are attractive to
      many applications because visible light has superior penetration and causes far
      less damage to organic molecules than UV. Herein, we report that self-doping of
      SnO2-x nanocrystals with Sn2+ red-shifts their absorption to the visible region
      and simultaneously produces oxygen vacancies, which can effectively scavenge
      photogenerated holes and thus enable the color switching of redox dyes using
      visible light. Wavelength-selective switching can also be achieved by coupling
      the photocatalytic activity of the SnO2-x NCs with the color-switching kinetics
      of different redox dyes. The fast light response enables the further fabrication
      of a solid film that can be repeatedly written on using a visible laser pen or
      projection printing through a photomask. This discovery represents a big step
      forward towards practical applications, especially in areas in which safety
      issues and photodamage by UV light are of concern.

PMID- 28508469
TI  - Defect Chemistry of Nonprecious-Metal Electrocatalysts for Oxygen Reactions.
AB  - Oxygen electrocatalysis, including the oxygen-reduction reaction (ORR) and oxygen
      evolution reaction (OER), is a critical process for metal-air batteries.
      Therefore, the development of electrocatalysts for the OER and the ORR is of
      essential importance. Indeed, various advanced electrocatalysts have been
      designed for the ORR or the OER; however, the origin of the advanced activity of
      oxygen electrocatalysts is still somewhat controversial. The enhanced activity is
      usually attributed to the high surface areas, the unique facet structures, the
      enhanced conductivities, or even to unclear synergistic effects, but the
      importance of the defects, especially the intrinsic defects, is often neglected.
      More recently, the important role of defects in oxygen electrocatalysis has been
      demonstrated by several groups. To make the defect effect clearer, the recent
      development of this concept is reviewed here and a novel principle for the design
      of oxygen electrocatalysts is proposed. An overview of the defects in carbon
      based, metal-free electrocatalysts for ORR and various defects in metal
      oxides/selenides for OER is also provided. The types of defects and controllable
      strategies to generate defects in electrocatalysts are presented, along with
      techniques to identify the defects. The defect-activity relationship is also
      explored by theoretical methods.

PMID- 28508470
TI  - Catalytic Asymmetric Inverse-Electron-Demand Hetero-Diels-Alder Reactions.
AB  - In this review, the recent developments in catalytic asymmetric inverse-electron
      demand hetero-Diels-Alder reaction, which is recognized as one of the most
      powerful routes to construct highly functionalized and enantioenriched six
      membered heterocycles, are described. The article is organized on the basis of
      different kinds of electron-deficient heterodienes, including alpha,beta
      unsaturated ketones/aldehydes, o-benzoquinones, alpha,beta-unsaturated imines, N
      aryl imines, o-benzoqinone imides, and other aza-olefins.

PMID- 28508471
TI  - Needleless emulsion electrospinning for the regulated delivery of susceptible
      proteins.
AB  - In the present work, we developed a novel needleless emulsion electrospinning
      technique that improves the production rate of the core/shell production process.
      The nanofibres are based on poly-epsilon-caprolactone (PCL) as a continuous phase
      combined with a droplet phase based on Pluronic F-68 (PF-68). The PCL-PF-68
      nanofibres show a time-regulated release of active molecules. Needleless emulsion
      electrospinning was used to encapsulate a diverse set of compounds to the core
      phase [i.e. 5-(4,6-dichlorotriazinyl) aminofluorescein -PF-68, horseradish
      peroxidase, Tetramethylrhodamine-dextran, insulin growth factor-I, transforming
      growth factor-beta and basic fibroblast growth factor]. In addition, the PF-68
      facilitates the preservation of the bioactivity of delivered proteins. The
      system's potential was highlighted by an improvement in the metabolic activity
      and proliferation of mesenchymal stem cells. The developed system has the
      potential to deliver susceptible molecules in tissue-engineering applications.

PMID- 28508472
TI  - Fatal Ingestion of Chlumsky Disinfectant Solution.
AB  - A 32-year-old pregnant woman in the 25th week of pregnancy underwent oral glucose
      tolerance screening at the diabetologist's. Later that day, she was found dead in
      her apartment possibly poisoned with Chlumsky disinfectant solution (solutio
      phenoli camphorata). An autopsy revealed chemical burns in the digestive system.
      The lungs and the brain showed signs of severe edema. The blood of the woman and
      fetus was analyzed using gas chromatography with mass spectrometry and revealed
      phenol, its metabolites (phenyl glucuronide and phenyl sulfate) and camphor. No
      ethanol was found in the blood samples. Both phenol and camphor are contained in
      Chlumsky disinfectant solution, which is used for disinfecting surgical equipment
      in healthcare facilities. Further investigation revealed that the deceased woman
      had been accidentally administered a disinfectant instead of a glucose solution
      by the nurse, which resulted in acute intoxication followed by the death of the
      pregnant woman and the fetus.

PMID- 28508473
TI  - Vertical Charge Transport via Small Polaron Hopping within TIPS-Pentacene
      Lamellar Single Crystal.
AB  - A modified liquid method is employed to grow an ultralarge 6,13
      bis(triisopropylsilylethynyl)pentacene crystal, ensuring fabrication and
      measurements of the two terminal devices. The hole transport mechanism is studied
      by analyzing the space charge limited currents (SCLCs) at various temperatures.
      Modified SCLC theory with a small polaron hopping model is developed and employed
      to successfully simulate the I-V curves. Values of effective hopping distance,
      transfer integral, and reorganization energy are extracted and reasonably
      discussed. A scenario is suggested that hopping transport takes place from one
      molecule to its nearest neighbor along the c-axis, with every molecule acting as
      a trapping center.

PMID- 28508474
TI  - Interrogation of a PS1-Based Photocathode by Means of Scanning
      Photoelectrochemical Microscopy.
AB  - In the development of photosystem-based energy conversion devices, the in-depth
      understanding of electron transfer processes involved in photocurrent generation
      and possible charge recombination is essential as a basis for the development of
      photo-bioelectrochemical architectures with increased efficiency. The evaluation
      of a bio-photocathode based on photosystem 1 (PS1) integrated within a redox
      hydrogel by means of scanning photoelectrochemical microscopy (SPECM) is
      reported. The redox polymer acts as a conducting matrix for the transfer of
      electrons from the electrode surface to the photo-oxidized P700 centers within
      PS1, while methyl viologen is used as charge carrier for the collection of
      electrons at the reduced FB site of PS1. The analysis of the modified surfaces by
      SPECM enables the evaluation of electron-transfer processes by simultaneously
      monitoring photocurrent generation at the bio-photoelectrode and the associated
      generation of reduced charge carriers. The possibility to visualize charge
      recombination processes is illustrated by using two different electrode
      materials, namely Au and p-doped Si, exhibiting substantially different electron
      transfer kinetics for the reoxidation of the methyl viologen radical cation used
      as freely diffusing charge carrier. In the case of p-doped Si, a slower
      recombination kinetics allows visualization of methyl viologen radical cation
      concentration profiles from SPECM approach curves.

PMID- 28508475
TI  - Functional properties of peripheral CD8+  T cells in patients with repeated
      implantation failure.
AB  - CD8+ T cells are the main candidates to recognize and respond to fetal HLA-C at
      the fetal-maternal interface, but data on the amount of peripheral CD8+ T cells
      and their functions during the window of implantation in recurrent implantation
      failure (RIF) patients are limited. Peripheral blood was obtained from 56 women
      with RIF and 16 fertile women in the mid-luteal phase of the menstrual cycle, and
      the CD8+ T cells were determined by FACS analysis. No statistical differences in
      the proportion of peripheral CD8+ T cells were observed among the women with RIF
      and the control group. However, the levels of IFN-gamma+ and TNF-alpha+ CD8+ T
      cells in the RIF group were significantly higher than those in the control group.
      The cytolytic activity and regulatory proportion of CD8+ T cells in RIF were
      similar to that in the control group. Our data indicated that the elevated
      expression levels of IFN-gamma and TNF-alpha in peripheral CD8+ T cells may
      contribute to an impaired immune tolerance in women with RIF.

PMID- 28508476
TI  - Magnetic resonance electrical properties tomography for small anomalies using
      boundary conditions: A simulation study.
AB  - PURPOSE: Magnetic resonance electrical property tomography (MREPT) is an emerging
      imaging modality using measured B1 maps from magnetic resonance imaging (MRI) to
      measure a distribution of electric conductivity and permittivity of the subject
      at the Larmor frequency. Conventional MREPT approaches at single transmit channel
      system using the Helmholtz equation rely on an assumption that conductivity and
      permittivity of the subject are locally homogeneous. For small tissue structures
      and tissue boundaries, in which the assumption of locally homogeneous
      conductivity and permittivity does not hold, the reconstructed conductivity
      values deviated from the actual values, so called "Boundary Artifacts." The aim
      of this study is to propose new reconstruction processes based on time-harmonic
      Maxwell's equations to reconstruct conductivity for small tissue structures and
      tissue boundaries. METHODS: Instead of removing the electric fields from the
      equations as done in the Helmholtz equation, three key identities of circularly
      polarized and longitudinal components of electric fields, circularly polarized
      component of magnetic fields, and electric properties from time-harmonic
      Maxwell's equations are derived. Based on the three key identities, the proposed
      reconstruction methods determine conductivity, permittivity, and circularly
      polarized component and longitudinal component of electric fields using the
      measured H1+ . In each iterative step, estimated conductivity, permittivity,
      electric fields, and artifact-free mask region, Omega, where the contribution of
      the boundary artifacts is small, were updated. Using the estimated values in the
      artifact-free mask region as boundary conditions, the estimates beyond the mask
      region were updated. EM simulations were performed on three types of numerical
      phantoms with very small regions of homogeneous conductivity and permittivity.
      The performance of the proposed methods was evaluated using the simulated
      electric and magnetic fields. RESULTS: For the numerical simulation model, the
      proposed methods significantly reduced the boundary artifacts compared to
      conventional methods using Helmholtz equations. In addition, previous methods
      using the Helmholtz equation could measure conductivity of only large anomalies,
      but the proposed method can measure the conductivity of the small compartments
      whose size is 2-3 voxels. The proposed approaches are compatible with spatial
      filtering which can be used to reduce noise. If a good image segmentation is
      available as a prior information, better initial boundary conditions can be
      estimated, and thus the proposed approach can be more accurate for small tissue
      structures. CONCLUSIONS: The proposed reconstruction method not only determines
      electrical properties, but also circularly polarized component and longitudinal
      component of electric fields using an iterative process. The proposed method can
      quantitatively detect the conductivity of the small anomalies better than
      conventional methods.

PMID- 28508477
TI  - The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and
      insulin resistance.
AB  - : Cellular repressor of E1A-stimulated genes (CREG), a novel cellular
      glycoprotein, has been identified as a suppressor of various cardiovascular
      diseases because of its capacity to reduce hyperplasia, maintain vascular
      homeostasis, and promote endothelial restoration. However, the effects and
      mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown.
      Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates
      high-fat diet and leptin deficiency-induced (ob/ob) adverse effects such as
      obesity, hepatic steatosis, and metabolic disorders, whereas a beneficial effect
      is conferred by CREG overexpression. Additional experiments demonstrated that c
      Jun N-terminal kinase 1 (JNK1) but not JNK2 is largely responsible for the
      protective effect of CREG on the aforementioned pathologies. Notably, JNK1
      inhibition strongly prevents the adverse effects of CREG deletion on steatosis
      and related metabolic disorders. Mechanistically, CREG interacts directly with
      apoptosis signal-regulating kinase 1 (ASK1) and inhibits its phosphorylation,
      thereby blocking the downstream MKK4/7-JNK1 signaling pathway and leading to
      significantly alleviated obesity, insulin resistance, and hepatic steatosis.
      Importantly, dramatically reduced CREG expression and hyperactivated JNK1
      signaling was observed in the livers of nonalcoholic fatty liver disease (NAFLD)
      patients, suggesting that CREG might be a promising therapeutic target for NAFLD
      and related metabolic diseases. CONCLUSION: The results of our study provides
      evidence that CREG is a robust suppressor of hepatic steatosis and metabolic
      disorders through its direct interaction with ASK1 and the resultant inactivation
      of ASK1-JNK1 signaling. This study offers insights into NAFLD pathogenesis and
      its complicated pathologies, such as obesity and insulin resistance, and paves
      the way for disease treatment through targeting CREG. (Hepatology 2017;66:834
      854).

PMID- 28508478
TI  - Accuracy of genomic within-family selection in aquaculture breeding programmes.
AB  - In aquaculture breeding programmes, selection within families cannot be applied
      for traits that cannot be recorded on the candidates (e.g., disease resistance or
      fillet quality). However, this problem can be overcome if genomic evaluation is
      used. Within-family genomic evaluation has been proposed for these programmes as
      large family sizes are available and substantial levels of linkage disequilibrium
      (LD) within families can be attained with a limited number of markers even in
      populations in global linkage equilibrium. Here, we compare by computer
      simulation: (i) within-family and population-wide LD; and (ii) the accuracy of
      within-family genomic selection when genomic evaluations are carried out either
      at the population level or within families. The population simulated was composed
      by a varying number of families of full-sibs (half for training and half for
      testing). The results indicate that, to practice within-family selection,
      performing the genomic evaluation separately for each family using only molecular
      information from the family could be recommended for populations either in
      linkage equilibrium or with a low level of disequilibrium.

PMID- 28508479
TI  - Prediction of complex traits: Conciliating genetics and statistics.
AB  - This review focuses on methods used to predict complex traits. Main
      characteristics of prediction approaches are given: the deterministic or
      stochastic nature of prediction, the objects of prediction, the sources of
      information and the main statistical methods. Sources of information discussed
      are the traditional genealogies and phenotypes, nucleotide sequences, expression
      data and epigenetics marks. Statistical methods are presented as successive
      degrees of generalization from the definition of the conditional expectation as
      the prediction rule, to best linear unbiased prediction, then Bayesian and,
      recently, machine learning methods, including meta-methods. We highlight the
      contributions of Daniel Gianola to this methodological evolution.

PMID- 28508481
TI  - A comparison of identity-by-descent and identity-by-state matrices that are used
      for genetic evaluation and estimation of variance components.
AB  - The genetic covariance matrix conditional on pedigree is proportional to the
      pedigree-based additive relationship matrix (PARM), which is twice the matrix of
      identity-by-descent (IBD) probabilities. In genomic prediction, IBD probabilities
      in the PARM, which are expected genetic similarities between relatives that are
      derived from the pedigree, are substituted by realized similarities that are
      derived from genotypes to obtain a genomic additive relationship matrix (GARM).
      Different definitions of similarity lead to different GARMs, and two commonly
      used GARMS are the matrix G, which is based on an allele substitution effect
      model, and the matrix T, which is based on an allele effect model. We show that
      although the two matrices T and G are not proportional, they give identical
      predictions of differences between breeding values. When genomic information is
      used for variance component estimation, the GARM Gx is computed from genotype
      covariates that have been standardized to have unit variance. That approach is
      equivalent to fitting a random regression model using the same standardized
      covariates. We show that under Hardy-Weinberg and linkage equilibria (LE) that
      the genetic variance is ksigmagamma2, where sigmagamma2 is the variance of a
      randomly sampled element from the vector of k substitution effects. However, if
      linkage disequilibrium (LD) has been generated through selection, covariances
      between genotypes at different loci will be negative, and therefore, the additive
      genetic variance will be lower than ksigmagamma2. When the GARM Gx is assumed to
      be proportional to the genetic covariance matrix, the parameter being estimated
      is ksigmagamma2. We have demonstrated by simulation that ksigmagamma2
      overestimates the additive genetic variance when LD is generated by selection. We
      argue that unlike the PARM, GARMs are not proportional to a genetic covariance
      matrix conditional on the observed causal genotypes. The objective here is to
      recognize the difference between these covariance matrices and its implications.

PMID- 28508480
TI  - Beyond genomic selection: The animal model strikes back (one generation)!
AB  - Genome inheritance is by segments of DNA rather than by independent loci. We
      introduce the ancestral regression (AR) as a recursive system of simultaneous
      equations, with grandparental path coefficients as novel parameters. The
      information given by the pedigree in the AR is complementary with that provided
      by a dense set of genomic markers, such that the resulting linear function of
      grandparental BV is uncorrelated to the average of parental BV in the absence of
      inbreeding. AR is then connected to segmental inheritance by a causal
      multivariate Gaussian density for BV. The resulting covariance structure (Sigma)
      is Markovian, meaning that conditional on the BV of parents and grandparents, the
      BV of the animal is independent of everything else. Thus, an algorithm is
      presented to invert the resulting covariance structure, with a computing effort
      that is linear in the number of animals as in the case of the inverse additive
      relationship matrix.

PMID- 28508482
TI  - Solving efficiently large single-step genomic best linear unbiased prediction
      models.
AB  - Single-step genomic BLUP (ssGBLUP) requires a dense matrix of the size equal to
      the number of genotyped animals in the coefficient matrix of mixed model
      equations (MME). When the number of genotyped animals is high, solving time of
      MME will be dominated by this matrix. The matrix is the difference of two inverse
      relationship matrices: genomic (G) and pedigree (A22 ). Different approaches were
      used to ease computations, reduce computing time and improve numerical stability.
      Inverse of A22 can be computed as A22-1=A22-A21A11-1A12 where Aij , i, j = 1,2,
      are sparse sub-matrices of A-1 , and numbers 1 and 2 refer to non-genotyped and
      genotyped animals, respectively. Inversion of A11 was avoided by three
      alternative approaches: iteration on pedigree (IOP), matrix iteration in memory
      (IM), and Cholesky decomposition by CHOLMOD library (CM). For the inverse of G,
      the APY (algorithm for proven and young) approach using Cholesky decomposition
      was formulated. Different approaches to choose the APY core were compared. These
      approaches were tested on a joint genetic evaluation of the Nordic Holstein
      cattle for fertility traits and had 81,031 genotyped animals. Computing time per
      iteration was 1.19 min by regular ssGBLUP, 1.49 min by IOP, 1.32 min by IM, and
      1.21 min by CM. In comparison with the regular ssGBLUP, the total computing time
      decreased due to omitting the inversion of the relationship matrix A22 . When APY
      used 10,000 (20,000) animals in the core, the computing time per iteration was at
      most 0.44 (0.63) min by all the APY alternatives. A core of 10,000 animals in APY
      gave GEBVs sufficiently close to those by regular ssGBLUP but needed only 25% of
      the total computing time. The developed approaches to invert the two relationship
      matrices are expected to allow much higher number of genotyped animals than was
      used in this study.

PMID- 28508483
TI  - Genomic variance estimates: With or without disequilibrium covariances?
AB  - Whole-genome regression methods are often used for estimating genomic
      heritability: the proportion of phenotypic variance that can be explained by
      regression on marker genotypes. Recently, there has been an intensive debate on
      whether and how to account for the contribution of linkage disequilibrium (LD) to
      genomic variance. Here, we investigate two different methods for genomic variance
      estimation that differ in their ability to account for LD. By analysing flowering
      time in a data set on 1,057 fully sequenced Arabidopsis lines with strong
      evidence for diversifying selection, we observed a large contribution of
      covariances between quantitative trait loci (QTL) to the genomic variance. The
      classical estimate of genomic variance that ignores covariances underestimated
      the genomic variance in the data. The second method accounts for LD explicitly
      and leads to genomic variance estimates that when added to error variance
      estimates match the sample variance of phenotypes. This method also allows
      estimating the covariance between sets of markers when partitioning the genome
      into subunits. Large covariance estimates between the five Arabidopsis
      chromosomes indicated that the population structure in the data led to strong LD
      also between physically unlinked QTL. By consecutively removing population
      structure from the phenotypic variance using principal component analysis, we
      show how population structure affects the magnitude of LD contribution and the
      genomic variance estimates obtained with the two methods.

PMID- 28508484
TI  - Special Issue: Quantitative and statistical genetics-papers in honour of Daniel
      Gianola.

PMID- 28508485
TI  - "Conversion" of epistatic into additive genetic variance in finite populations
      and possible impact on long-term selection response.
AB  - The role of epistasis in understanding the genetic architecture and variation of
      quantitative traits and its role, if any, in artificial selection and livestock
      improvement more generally has a long and sometimes controversial history. Its
      presence has been clearly demonstrated in, for example, laboratory experiments,
      but the amount of variation it contributes is likely to be small in outbred
      populations. In a finite population, although additive x additive epistatic
      variance is lost by genetic drift, it also contributes by conversion to additive
      variance through drift sampling and therefore has a potential indirect role in
      medium and long-term selection response, with superficial similarity to and hard
      to distinguish from mutation. Whilst predictions of response require knowledge of
      genetic parameters, an infinitesimal model provides some analytic results.
      Otherwise there is little quantitative information relevant to animal populations
      on which to judge this potential role of epistasis and reach firm conclusions.

PMID- 28508486
TI  - Pedigree-based estimation of covariance between dominance deviations and additive
      genetic effects in closed rabbit lines considering inbreeding and using a
      computationally simpler equivalent model.
AB  - Inbreeding generates covariances between additive and dominance effects (breeding
      values and dominance deviations). In this work, we developed and applied models
      for estimation of dominance and additive genetic variances and their covariance,
      a model that we call "full dominance," from pedigree and phenotypic data.
      Estimates with this model such as presented here are very scarce both in
      livestock and in wild genetics. First, we estimated pedigree-based condensed
      probabilities of identity using recursion. Second, we developed an equivalent
      linear model in which variance components can be estimated using closed-form
      algorithms such as REML or Gibbs sampling and existing software. Third, we
      present a new method to refer the estimated variance components to meaningful
      parameters in a particular population, i.e., final partially inbred generations
      as opposed to outbred base populations. We applied these developments to three
      closed rabbit lines (A, V and H) selected for number of weaned at the Polytechnic
      University of Valencia. Pedigree and phenotypes are complete and span 43, 39 and
      14 generations, respectively. Estimates of broad-sense heritability are 0.07,
      0.07 and 0.05 at the base versus 0.07, 0.07 and 0.09 in the final generations.
      Narrow-sense heritability estimates are 0.06, 0.06 and 0.02 at the base versus
      0.04, 0.04 and 0.01 at the final generations. There is also a reduction in the
      genotypic variance due to the negative additive-dominance correlation. Thus, the
      contribution of dominance variation is fairly large and increases with inbreeding
      and (over)compensates for the loss in additive variation. In addition, estimates
      of the additive-dominance correlation are -0.37, -0.31 and 0.00, in agreement
      with the few published estimates and theoretical considerations.

PMID- 28508487
TI  - Accuracy of genomic breeding values revisited: Assessment of two established
      approaches and a novel one to determine the accuracy in two-step genomic
      prediction.
AB  - Selection decisions in genomic selection schemes are made based on genomic
      breeding values (GBV) of candidates. Thus, the accuracy of GBV is a relevant
      parameter, as it reflects the stability of prediction and the possibility that
      the GBV might change when more information becomes available. Accuracy of genomic
      prediction defined as the correlation between GBV and true breeding values (TBV),
      however, is difficult to assess, considering TBV of the candidates are not
      available in reality. In previous studies, several methods were proposed to
      assess the accuracy of GBV including methods using population parameters or
      parameters inferred from mixed-model equations. In practice, most approaches
      tended to overestimate the accuracy of genomic prediction. We thus tested
      approaches used in previous studies in order to assess the magnitude of bias.
      Analyses were performed based on simulated data under a variety of scenarios
      mimicking different livestock breeding programmes. Furthermore, we proposed a
      novel method and tested it both with simulated data and in a real Holstein data
      set. The new method provided a better prediction for the accuracy of GBV in the
      simulated scenarios.

PMID- 28508488
TI  - Modelling female fertility traits in beef cattle using linear and non-linear
      models.
AB  - Female fertility traits are key components of the profitability of beef cattle
      production. However, these traits are difficult and expensive to measure,
      particularly under extensive pastoral conditions, and consequently, fertility
      records are in general scarce and somehow incomplete. Moreover, fertility traits
      are usually dominated by the effects of herd-year environment, and it is
      generally assumed that relatively small margins are kept for genetic improvement.
      New ways of modelling genetic variation in these traits are needed. Inspired in
      the methodological developments made by Prof. Daniel Gianola and co-workers, we
      assayed linear (Gaussian), Poisson, probit (threshold), censored Poisson and
      censored Gaussian models to three different kinds of endpoints, namely calving
      success (CS), number of days from first calving (CD) and number of failed oestrus
      (FE). For models involving FE and CS, non-linear models overperformed their
      linear counterparts. For models derived from CD, linear versions displayed better
      adjustment than the non-linear counterparts. Non-linear models showed
      consistently higher estimates of heritability and repeatability in all cases (h2 
      < 0.08 and r < 0.13, for linear models; h2  > 0.23 and r > 0.24, for non-linear
      models). While additive and permanent environment effects showed highly
      favourable correlations between all models (>0.789), consistency in selecting the
      10% best sires showed important differences, mainly amongst the considered
      endpoints (FE, CS and CD). In consequence, endpoints should be considered as
      modelling different underlying genetic effects, with linear models more
      appropriate to describe CD and non-linear models better for FE and CS.

PMID- 28508489
TI  - Prediction of whole-genome risk for selection and management of hyperketonemia in
      Holstein dairy cattle.
AB  - Hyperketonemia (HYK), a common early postpartum health disorder characterized by
      elevated blood concentrations of beta-hydroxybutyrate (BHB), affects millions of
      dairy cows worldwide and leads to significant economic losses and animal welfare
      concerns. In this study, blood concentrations of BHB were assessed for 1,453
      Holstein cows using electronic handheld meters at four time points between 5 and
      18 days postpartum. Incidence rates of subclinical (1.2 <= maximum BHB <= 2.9
      mmol/L) and clinical ketosis (maximum BHB >= 3.0 mmol/L) were 24.0 and 2.4%,
      respectively. Variance components, estimated breeding values, and predicted HYK
      phenotypes were computed on the original, square-root, and binary scales.
      Heritability estimates for HYK ranged from 0.058 to 0.072 in pedigree-based
      analyses, as compared to estimates that ranged from 0.071 to 0.093 when pedigrees
      were augmented with 60,671 single nucleotide polymorphism genotypes of 959 cows
      and 801 male ancestors. On average, predicted HYK phenotypes from the genome
      enhanced analysis ranged from 0.55 mmol/L for first-parity cows in the best
      contemporary group to 1.40 mmol/L for fourth-parity cows in the worst
      contemporary group. Genome-enhanced predictions of HYK phenotypes were more
      closely associated with actual phenotypes than pedigree-based predictions in five
      fold cross-validation, and transforming phenotypes to reduce skewness and
      kurtosis also improved predictive ability. This study demonstrates the
      feasibility of using repeated cowside measurement of blood BHB concentration in
      early lactation to construct a reference population that can be used to estimate
      HYK breeding values for genomic selection programmes and predict HYK phenotypes
      for genome-guided management decisions.

PMID- 28508490
TI  - Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2
      Aminofurans From N-Tosylhydrazone-Bearing Thiocarbamates.
AB  - An efficient and convenient synthesis of valuable disulfanes and
      benzenesulfonothioates, having a 2-aminofuran framework, has been developed by
      employing a copper-catalyzed transformation of readily available N-tosylhydrazone
      bearing thiocarbamates. This method features an inexpensive metal catalyst, mild
      reaction conditions, good functional-group tolerance, short reaction times, and
      delivers valuable and complex products. A copper carbene generated from an N
      tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the
      transformation and it triggers the subsequent cascade. Remarkably, the Ts anion
      released from N-tosylhydrazone further serves as a nucleophile, thus rendering
      the formation of benzenesulfonothioates under controlled conditions.

PMID- 28508491
TI  - Implementation of absolute quantification in small-animal SPECT imaging: Phantom
      and animal studies.
AB  - PURPOSE: Presence of photon attenuation severely challenges quantitative accuracy
      in single-photon emission computed tomography (SPECT) imaging. Subsequently,
      various attenuation correction methods have been developed to compensate for this
      degradation. The present study aims to implement an attenuation correction method
      and then to evaluate quantification accuracy of attenuation correction in small
      animal SPECT imaging. METHODS: Images were reconstructed using an iterative
      reconstruction method based on the maximum-likelihood expectation maximization
      (MLEM) algorithm including resolution recovery. This was implemented in our
      designed dedicated small-animal SPECT (HiReSPECT) system. For accurate
      quantification, the voxel values were converted to activity concentration via a
      calculated calibration factor. An attenuation correction algorithm was developed
      based on the first-order Chang's method. Both phantom study and experimental
      measurements with four rats were used in order to validate the proposed method.
      RESULTS: The phantom experiments showed that the error of -15.5% in the
      estimation of activity concentration in a uniform region was reduced to +5.1%
      when attenuation correction was applied. For in vivo studies, the average
      quantitative error of -22.8 +/- 6.3% (ranging from -31.2% to -14.8%) in the
      uncorrected images was reduced to +3.5 +/- 6.7% (ranging from -6.7 to +9.8%)
      after applying attenuation correction. CONCLUSION: The results indicate that the
      proposed attenuation correction algorithm based on the first-order Chang's
      method, as implemented in our dedicated small-animal SPECT system, significantly
      improves accuracy of the quantitative analysis as well as the absolute
      quantification.

PMID- 28508492
TI  - Comparison of vertical and horizontal swimming behaviour of the weather loach
      Misgurnus anguillicaudatus.
AB  - Experiments on the swimming kinetics and behaviour of weather loach Misgurnus
      anguillicaudatus showed that horizontal swim speed was significantly greater than
      swim speeds when ascending to or descending from the water surface to gulp air.
      Vertical swimming speeds during ascending or descending were similar. Misgurnus
      anguillicaudatus swam unsteadily during vertical movements compared with
      horizontal movements.

PMID- 28508495
TI  - What is the best imaging technique in discriminating dementia with Lewy bodies
      from other dementias?

PMID- 28508494
TI  - High-dose prednisolone after intravenous methylprednisolone improves prognosis of
      acute exacerbation in idiopathic interstitial pneumonias.
AB  - BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) of idiopathic pulmonary
      fibrosis (IPF) (AE-IPF) is a poor prognostic disorder. AE is also reported to
      occur in other idiopathic interstitial pneumonias (IIPs). There are limited data
      available regarding the effectiveness of treatment for AE-IIPs. The objective of
      this study was to clarify the prognostic impact of the initial dose of
      prednisolone (PSL) for treating AE-IIPs. METHODS: Eighty-five patients with AE
      IIPs, diagnosed according to the criteria of the Japanese Respiratory Society,
      were enrolled in this study (IPF/non-IPF: 63/22 patients) from 2004 to 2013. We
      performed multivariate Cox proportional hazard regression analysis to identify
      poor prognostic factors. HRCT patterns at the onset of AE-IIPs were classified as
      diffuse or non-diffuse. We evaluated the prognostic significance of the initial
      dose of PSL by adjusting for other prognostic factors. RESULTS: Median survival
      time (MST) after AE-IIPs diagnosis was 49 days. MST of AE-IPF and AE-non-IPF was
      39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher
      serum surfactant protein-D at AE diagnosis, long-term oxygen therapy (LTOT)
      before AE and positive pressure ventilation (PPV) use for AE were significant
      poor prognostic factors for all patients, as were LTOT before AE and lower serum
      IgG for no-PPV patients. High-dose PSL >= 0.6 mg/kg was a significant prognostic
      factor for no-PPV patients after adjusting for other prognostic factors.
      CONCLUSION: We concluded that a dose of PSL >= 0.6 mg/kg after i.v. high-dose
      methylprednisolone therapy should be recommended for the treatment of AE-IIPs.

PMID- 28508496
TI  - Effect of sex on the association of isokinetic quadriceps strength with
      hypertension among older Americans.

PMID- 28508493
TI  - Exome sequencing reveals novel genetic loci influencing obesity-related traits in
      Hispanic children.
AB  - OBJECTIVE: To perform whole exome sequencing in 928 Hispanic children and
      identify variants and genes associated with childhood obesity. METHODS: Single
      nucleotide variants (SNVs) were identified from Illumina whole exome sequencing
      data using integrated read mapping, variant calling, and an annotation pipeline
      (Mercury). Association analyses of 74 obesity-related traits and exonic variants
      were performed using SeqMeta software. Rare autosomal variants were analyzed
      using gene-based association analyses, and common autosomal variants were
      analyzed at the SNV level. RESULTS: (1) Rare exonic variants in 10 genes and 16
      common SNVs in 11 genes that were associated with obesity traits in a cohort of
      Hispanic children were identified, (2) novel rare variants in peroxisome
      biogenesis factor 1 (PEX1) associated with several obesity traits (weight, weight
      z score, BMI, BMI z score, waist circumference, fat mass, trunk fat mass) were
      discovered, and (3) previously reported SNVs associated with childhood obesity
      were replicated. CONCLUSIONS: Convergence of whole exome sequencing, a family
      based design, and extensive phenotyping discovered novel rare and common variants
      associated with childhood obesity. Linking PEX1 to obesity phenotypes poses a
      novel mechanism of peroxisomal biogenesis and metabolism underlying the
      development of childhood obesity.

PMID- 28508497
TI  - Personality traits and behavioral disturbances in dementia: A new risk factor?

PMID- 28508498
TI  - Femoral osteoporosis is more common than lumbar osteoporosis in patients with
      Werner syndrome.

PMID- 28508499
TI  - Author's reply "What is the best neuroimaging technique in discriminating
      dementia with Lewy bodies from Alzheimer's disease?"

PMID- 28508500
TI  - Hyponatremia after initiation of angiotensin-converting enzyme inhibitor in a
      geriatric patient with chronic heart failure: A case of mineralocorticoid
      responsive hyponatremia of the elderly.

PMID- 28508501
TI  - Case of insulinoma manifesting as hyperinsulinemia after discontinuing quetiapine
      in an elderly patient with delirium.

PMID- 28508502
TI  - Reduced brain-derived neurotrophic factor is associated with cognitive
      dysfunction in patients with chronic heart failure.

PMID- 28508504
TI  - AibA/AibB Induces an Intramolecular Decarboxylation in Isovalerate Biosynthesis
      by Myxococcus xanthus.
AB  - Isovaleryl coenzyme A (IV-CoA) is an important precursor for iso-fatty acids and
      lipids. It acts in the development of myxobacteria, which can produce this
      compound from acetyl-CoA through alternative IV-CoA biosynthesis (aib). A central
      reaction of aib is catalyzed by AibA/AibB, which acts as a cofactor-free
      decarboxylase despite belonging to the family of CoA-transferases. We developed
      an efficient expression system for AibA/AibB that allowed the determination of
      high-resolution crystal structures in complex with different ligands. Through
      mutational studies, we show that an active-site cysteine previously proposed to
      be involved in decarboxylation is not required for activity. Instead, AibA/AibB
      seems to induce an intramolecular decarboxylation by binding its substrate in a
      hydrophobic cavity and forcing it into a bent conformation. Our study opens
      opportunities for synthetic biology studies, since AibA/AibB may be suitable for
      the production of isobutene, a precursor of biofuels and chemicals.

PMID- 28508503
TI  - Expanding analytical options in sports drug testing: Mass spectrometric detection
      of prohibited substances in exhaled breath.
AB  - RATIONALE: Continuously refining and advancing the strategies and methods
      employed in sports drug testing is critical for efficient doping controls.
      Besides improving and expanding the spectrum of target analytes, alternative test
      matrices have warranted in-depth evaluation as they commonly allow for minimal
      /non-invasive and non-intrusive sample collection. In this study, the potential
      of exhaled breath (EB) as doping control specimen was assessed. METHODS: EB
      collection devices employing a non-woven electret-based air filter unit were used
      to generate test specimens, simulating a potential future application in doping
      controls. A multi-analyte sports drug testing approach configured for a subset of
      12 model compounds that represent specific classes of substances prohibited in
      sports (anabolic agents, hormone and metabolic modulators, stimulants, and beta
      blockers) was established using unispray liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) and applied to spiked and elimination study EB samples.
      The test method was characterized concerning specificity, assay imprecision, and
      limits of detection. RESULTS: The EB collection device allowed for retaining and
      extracting all selected model compounds from the EB aerosol. Following elution
      and concentration, LC/MS/MS analysis enabled detection limits between 5 and 100
      pg/filter and imprecisions ranging from 3% to 20% for the 12 selected model
      compounds. By means of EB samples from patients and participants of
      administration studies, the elimination of relevant compounds and, thus, their
      traceability in EB for doping control purposes, was investigated. Besides
      stimulants such as methylhexaneamine and pseudoephedrine, also the anabolic
      androgenic steroid dehydrochloromethyltestosterone, the metabolic modulator
      meldonium, and the beta-blocker bisoprolol was detected in exhaled breath.
      CONCLUSIONS: The EB aerosol has provided a promising proof-of-concept suggesting
      the expansion of this testing strategy as a complement to currently utilized
      sports drug testing programs.

PMID- 28508505
TI  - Rapid switch-off of the human myosin heavy chain IIX gene after heavy load muscle
      contractions is sustained for at least four days.
AB  - Long-term heavy load contractions decrease the relative amount of the myosin
      heavy chain (MHC) IIX isoform in human skeletal muscle, but the timing of the
      down-regulation in the short term is unknown. Untrained subjects performed two
      resistance bouts, in two consecutive days, with one leg, the other leg serving as
      a control (age 24+/-1, n=5). Muscle biopsies were obtained in both legs before,
      immediately after, and 24, 54, and 96 hours after exercise. Serial cryosection
      analysis combined immunohistochemistry and ATPase histochemistry with In Situ
      hybridization to identify the distribution of MHC isoforms and their
      corresponding transcripts, enabling identification of transitional fibers. Fibers
      positive solely for MHC IIX mRNA decreased in the exercised leg throughout the
      study period. At 96 hours post-exercise, no fibers solely expressed MHC IIX mRNA.
      In contrast, the number of fibers expressing MHC IIA mRNA increased throughout
      the study period. The percentage of fibers expressing mRNA for MHC I was
      unchanged in both legs at all time points. Pronounced depletion of glycogen in
      the MHC IIX fibers of the exercised leg verifies that the type IIX fibers were
      active during the heavy load contractions. Major mismatch between MHC at the mRNA
      and protein levels was only found in the fibers of the exercised leg. These data
      provide unequivocal in situ evidence of an immediate shutdown of the MHC IIX gene
      after resistance exercise. A further novel finding was that the silencing of the
      MHC IIX gene is sustained at least 4 days after removal of the stimulus.

PMID- 28508506
TI  - Low-Voltage Photodetectors with High Responsivity Based on Solution-Processed
      Micrometer-Scale All-Inorganic Perovskite Nanoplatelets.
AB  - All-inorganic photodetectors based on scattered CsPbBr3 nanoplatelets with
      lateral dimension as large as 10 um are fabricated, and the CsPbBr3 nanoplatelets
      are solution processed governed by a newly developed ion-exchange soldering
      mechanism. Under illumination of a 442 nm laser, the photoresponsivity of
      photodetectors based on these scattered CsPbBr3 nanoplatelets is as high as 34 A
      W-1 , which is the largest value reported from all-inorganic perovskite
      photodetectors with an external driven voltage as small as 1.5 V. Moreover, the
      rise and fall times are 0.6 and 0.9 ms, respectively, which are comparable to
      most of the state-of-the-art all-inorganic perovskite-based photodetectors. All
      the material synthesis and device characterization are conducted at room
      temperature in ambient air. This work demonstrates that the solution-processed
      large CsPbBr3 nanoplatelets are attractive candidates to be applied in low
      voltage, low-cost, ultra highly integrated optoelectronic devices.

PMID- 28508507
TI  - Detecting selection signatures between Duroc and Duroc synthetic pig populations
      using high-density SNP chip.
AB  - The development of high throughput genotyping techniques has facilitated the
      identification of selection signatures of pigs. The detection of genomic
      selection signals in a population subjected to differential selection pressures
      may provide insights into the genes associated with economically and biologically
      important traits. To identify genomic regions under selection, we genotyped 488
      Duroc (D) pigs and 155 D * Korean native pigs (DKNPs) using the Porcine SNP70K
      BeadChip. By applying the FST and extended haplotype homozygosity (EHH-Rsb)
      methods, we detected genes under directional selection associated with
      growth/stature (DOCK7, PLCB4, HS2ST1, FBP2 and TG), carcass and meat quality (TG,
      COL14A1, FBXO5, NR3C1, SNX7, ARHGAP26 and DPYD), number of teats (LOC100153159
      and LRRC1), pigmentation (MME) and ear morphology (SOX5), which are all mostly
      near or at fixation. These results could be a basis for investigating the
      underlying mutations associated with observed phenotypic variation. Validation
      using genome-wide association analysis would also facilitate the inclusion of
      some of these markers in genetic evaluation programs.

PMID- 28508508
TI  - End Functionalized Nonionic Water-Dispersible Conjugated Polymers.
AB  - 2,7-Dibromofluorene monomers carrying two or four oligo(ethylene glycol) (OEG)
      side chains are synthesized. Heck coupling between the monomers and 1,4
      divinylbenzene followed by end capping with [4-(4-bromophenoxy)butyl]carbamic
      acid tert-butyl ester leads to two nonionic water-dispersible poly(fluorene-alt
      1,4-divinylenephenylene)s end-functionalized with amine groups after hydrolysis.
      In water, the polymer with a lower OEG density (P1) has poor water dispersibility
      with a quantum yield of 0.24, while the polymer with a higher OEG density (P2)
      possesses excellent water-dispersibility with a high quantum yield of 0.45. Both
      polymers show fluorescence enhancement and blue-shifted absorption and emission
      maxima in the presence of surfactant sodium dodecyl sulfate and
      dodecyltrimethylammonium bromide. The polymers are also resistant to ionic
      strength with minimal nonspecific interactions to bovine serum albumin. When
      biotin is incorporated into the end of the polymer backbones through N
      hydroxysuccinimide/amine coupling reaction, the biotinylated polymers interact
      specifically with streptavidin on solid surface.

PMID- 28508509
TI  - Investigating the inter-subunit/subdomain interactions and motions relevant to
      disease mutations in the N-terminal domain of ryanodine receptors by molecular
      dynamics simulation.
AB  - The ryanodine receptors (RyR) are essential to calcium signaling in striated
      muscles, and numerous disease mutations have been identified in two RyR isoforms,
      RyR1 in skeletal muscle and RyR2 in cardiac muscle. A deep understanding of the
      activation/regulation mechanisms of RyRs has been hampered by the shortage of
      high-resolution structures and dynamic information for this giant tetrameric
      complex in different functional states. Toward elucidating the molecular
      mechanisms of disease mutations in RyRs, we performed molecular dynamics
      simulation of the N-terminal domain (NTD) which is not only the best-resolved
      structural component of RyRs, but also a hotspot of disease mutations. First, we
      simulated the tetrameric NTD of wild-type RyR1 and three disease mutants (K155E,
      R157Q, and R164Q) that perturb the inter-subunit interfaces. Our simulations
      identified a dynamic network of salt bridges involving charged residues at the
      inter-subunit/subdomain interfaces and disease-mutation sites. By perturbing this
      key network, the above three mutations result in greater flexibility with the
      highest inter-subunit opening probability for R157Q. Next, we simulated the
      monomeric NTD of RyR2 in the presence or absence of a central Cl- anion which is
      known to stabilize the interfaces between the three NTD subdomains (A, B, and C).
      We found that the loss of Cl- restructures the salt-bridge network near the Cl- 
      binding site, leading to rotations of subdomain A/B relative to subdomain C and
      enhanced mobility between the subdomains. This finding supports a mechanism for
      disease mutations in the NTD of RyR2 via perturbation of the Cl- binding. The
      rich structural and dynamic information gained from this study will guide future
      mutational and functional studies of the NTD of RyRs. Proteins 2017; 85:1633
      1644. (c) 2017 Wiley Periodicals, Inc.

PMID- 28508510
TI  - Impaired atrioventricular transport in patients with transposition of the great
      arteries palliated by atrial switch and preserved systolic right ventricular
      function: A magnetic resonance imaging study.
AB  - OBJECTIVES: We aimed (1) determine if systemic right ventricle filling parameters
      influence systemic right ventricle stroke volume in adult patients with D
      transposition of the great arteries (D-TGA) palliated by atrial switch, using
      cardiac magnetic resonance imaging and echocardiography, and (2) to study
      relationship of these diastolic parameters with exercise performance and BNP, in
      patients with preserved systolic systemic right ventricle function. DESIGN:
      Single-center, cross-sectional, prospective study. SETTING: In patients with D
      TGA palliated by atrial switch, diastolic dysfunction of the systemic right
      ventricle may precede systolic dysfunction. METHODS: Forty-five patients with D
      TGA and atrial switch and 45 age and sex-matched healthy subjects underwent
      cardiac magnetic resonance imaging and echocardiography. Filling flow-rates
      measured by phase-contrast cardiac magnetic resonance imaging were analyzed using
      customized software to estimate diastolic parameters and compared with exercise
      performance. RESULTS: In D-TGA, early filling of systemic right ventricle was
      impaired with a lower peak filling rate normalized by filling volume (Ef/FV
      measured by cardiac magnetic resonance imaging) and a higher early filling peak
      velocity normalized by early peak myocardial velocity (EUS /Ea measured by
      echocardiography) compared with controls (P <= .04). Stroke volume of systemic
      right ventricle showed a direct and significant association with pulmonary venous
      pathway size (respectively r = 0.50, P < .01). Systemic right atrial area and
      systemic right ventricle mass/volume index measured by cardiac magnetic resonance
      imaging, as well as Ef/FV were significantly correlated with exercise
      performances and BNP (P < .01). All correlations were independent of age, gender,
      body mass index and blood pressure. CONCLUSIONS: Systemic right ventricle pre
      load and stroke volume depend mainly on intraatrial pathway function. Moreover,
      systemic right ventricle remodeling and right atrial dysfunction impair systemic
      right ventricle filling, leading to BNP increase and exercise limitation. Cardiac
      magnetic resonance imaging should assess systemic right ventricle filling
      abnormalities in D-TGA patients.

PMID- 28508511
TI  - Clinical, nociceptive and psychological profiling to predict acute pain after
      total knee arthroplasty.
AB  - BACKGROUND: Pre-operative identification of high-pain responders for acute pain
      after total knee arthroplasty (TKA) could lead to targeted analgesic trials and
      individualized analgesic strategies to improve recovery and potentially reduce
      the risk of persistent post-surgical pain. The aim of this study was to use
      simple clinical tests and questionnaires to identify predictive nociceptive and
      psychological factors for acute post-TKA pain. METHODS: Sixty consecutive TKA
      patients were included in a prospective descriptive study of pain during a 5-m
      walk-test 24 h post-operatively as the primary outcome. Predictive variables
      collected prior to surgery included demographics, nociceptive testing (pressure
      pain threshold (PPT), cold pressor tolerance, electrical pain threshold and
      tolerance) and psychological profile (pain catastrophizing scale (PCS) and
      hospital anxiety and depression scale). The prediction of acute post-TKA pain was
      assessed by univariate analysis, logistic regressions and ROC curves. RESULTS:
      Reduced PPT on the arm and increased PCS were predictive variables for
      moderate/severe post-TKA pain 24 h after surgery (P = 0.007 and P = 0.026,
      respectively, R-squared 0.21) in the logistic regression model. Odds ratios were
      0.67 for a 50 kPa increased PPT and 1.36 for a 5 point increase in PCS. A
      predictive model with cut-off values of PPT <= 245 kPa and PCS>= 8 point had a
      sensitivity of 71.4 and a specificity of 62.5. CONCLUSION: Pre-operative
      widespread pressure pain hypersensitivity and pain catastrophizing are predictive
      of moderate severe post-TKA pain. If validated in a larger population, the
      clinically applicable tests should be considered in future interventions aiming
      to minimize post-operative pain in high-risk patients.

PMID- 28508512
TI  - Ultralight Multifunctional Carbon-Based Aerogels by Combining Graphene Oxide and
      Bacterial Cellulose.
AB  - Nanostructured carbon aerogels with outstanding physicochemical properties have
      exhibited great application potentials in widespread fields and therefore
      attracted extensive attentions recently. It is still a challenge so far to
      develop flexible and economical routes to fabricate high-performance nanocarbon
      aerogels, preferably based on renewable resources. Here, ultralight and
      multifunctional reduced graphene oxide/carbon nanofiber (RGO/CNF) aerogels are
      fabricated from graphene oxide and low-cost, industrially produced bacterial
      cellulose by a three-step process of freeze-casting, freeze-drying, and
      pyrolysis. The prepared RGO/CNF aerogel possesses a very low apparent density in
      the range of 0.7-10.2 mg cm-3 and a high porosity up to 99%, as well as a
      mechanically robust and electrically conductive 3D network structure, which makes
      it to be an excellent candidate as absorber for oil clean-up and an ideal
      platform for constructing flexible and stretchable conductors.

PMID- 28508513
TI  - Synthesis and Trapping of Iminoboranes by M=B/C=N Bond Metathesis.
AB  - Although the metathesis of metal-boron double bonds with elemental chalcogenides
      is an established process, no similar reactivity has been observed with element
      nitrogen bonds. Such a reaction would provide a new route to iminoborane
      compounds (RB=NR'), which have recently experienced renewed synthetic interest.
      Herein, we present the first observation of M=B/C=N metathesis reactions, which
      led to the isolation of a stable iminoborane in addition to further iminoborane
      cycloaddition products.

PMID- 28508514
TI  - Migraine prevalence in inflammatory bowel disease patients: A tertiary-care
      centre cross-sectional study.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory
      conditions that predominately affect the gastrointestinal tract and can induce
      abdominal pain. Besides, many IBD patients complain about headaches in daily
      practice. The objective was to assess the prevalence of headaches, including
      migraines and pain with neuropathic characteristics (NC), in IBD patients
      compared to historical controls from the general population. METHODS: Overall,
      203 consecutive tertiary-care centre patients completed validated self
      administered questionnaires and benefitted from a clinical evaluation performed
      by an IBD physician at the same time. RESULTS: In our cohort, 75% of the patients
      experienced pain in the previous 3 months. Migraine prevalence was two-fold
      higher in IBD patients compared to the general population (41% vs. 21.3%, p <
      0.001). Migraine was associated with a younger age, female gender and higher
      depression scores. Although migraine impact was very important for 30% of the
      patients (61/203), specific acute therapeutics were prescribed in only 22% of
      cases (18/83). Chronic pain with NC was more frequent than in the general
      population (11.3% vs. 6.9%, p = 0.012) and was strongly associated with the
      presence of extra-intestinal manifestations (p < 0.001). Abdominal pain concerned
      19% of the patients during the previous week and was, as expected, associated
      with disease activity. CONCLUSIONS: Migraine prevalence is strongly increased in
      IBD patients followed in tertiary care. A systematic screening for migraine
      should be done by IBD physicians in daily practice to provide adequate
      therapeutics. Further studies are needed to confirm whether migraine should be
      classified as IBD extra-intestinal manifestations. SIGNIFICANCE: Migraine
      prevalence was two-fold higher in IBD patients compared to the general
      population, was generally poorly treated and a systematic screening for migraine
      should be done by IBD physicians in daily practice to provide adequate
      therapeutics.

PMID- 28508515
TI  - Extra oral digital scanning and imaging superimposition for volume analysis of
      bone remodeling after tooth extraction with and without 2 types of particulate
      porcine mineral insertion: A randomized controlled trial.
AB  - BACKGROUND: Incorporation of bone substitute material into the extraction socket
      could minimize the edentulous ridge volume loss or maximize the bone formation
      within the healing area. PURPOSE: The aim of the study was to test the
      effectiveness in maintaining the volumetric contour of fresh extraction sockets
      grafted with or without 2 types of porcine biomaterials and covered with a
      resorbable barrier. MATERIALS AND METHODS: In the present multi-center single
      blind randomized control trial, 55 patients underwent 1-tooth extraction, were
      surveyed, and randomly allocated to control- (25 sites, nat-group) or test groups
      (15 sites grafted with pre-hydrated collagenated cortico-cancellous porcine bone,
      coll-group, and 15 with cortical porcine bone, cort-group). Before extraction,
      and then 4 months later, contours of the sockets were acquired through a laser
      scanner, voxelized, and ghosts of each patient were superimposed with a matrix
      laboratory. Volumetric and area evaluations of the virtual superimposed models
      were performed with dentascan tools to create a volume of interest extending
      between the 2 residual teeth. Intra- and inter-group comparisons of the outcomes
      were performed. Non-parametric tests were applied with a level of significance
      set at P < .05. RESULTS: Intergroup analysis at 4 months' survey revealed that
      percentage loss of alveolar ridge volume of the coll-group (28.8% +/- 8.8%) and
      of the cort-group (30.2% +/- 7.1%) was significantly lower (P < .0001) than that
      of the naturally-healing group (46.4% +/- 4.1%). No statistically-significant
      differences in outcomes were observed between the 2 test groups at any of the
      observation periods. Moreover, tooth position (bicuspids vs molars) seemed to
      affect neither volume loss nor basal shrinkage. CONCLUSION: At the 4-month
      analysis both test groups showed reduced bone loss when compared to naturally
      healing sockets. However, the 2 grafting materials were not able to preserve the
      alveolar crest, and a reduction close to 30% in the estimates was registered
      after healing.

PMID- 28508517
TI  - On-demand Antimicrobial Treatment with Antibiotic-Loaded Porous Silicon Capped
      with a pH-Responsive Dual Plasma Polymer Barrier.
AB  - Chronic wounds are a major socio-economic problem. Bacterial infections in such
      wounds are a major contributor to lack of wound healing. An early indicator of
      wound infection is an increase in pH of the wound fluid. Herein, we describe the
      development of a pH-responsive drug delivery device that can potentially be used
      for wound decontamination in situ and on-demand in response to an increase in the
      pH of the wound environment. The device is based on a porous silicon film that
      provides a reservoir for encapsulation of an antibiotic within the pores. Loaded
      porous silicon is capped with dual plasma polymer layers of poly(1,7-octadiene)
      and poly(acrylic acid), which provide a pH-responsive barrier for on-demand
      release of the antibiotic. We demonstrate that release of the antibiotic is
      inhibited in aqueous buffer at pH 5, whereas the drug is released in a
      sustainable manner at pH 8. Importantly, the released drug was bacteriostatic
      against the Pseudomonas aeruginosa wound pathogen. In the future, incorporation
      of the delivery device into wound dressings could potentially be utilized for non
      invasive decontamination of wounds.

PMID- 28508518
TI  - Alcohol marketing and youth drinking in Asia.

PMID- 28508519
TI  - Fetal cardiac remodeling in twin pregnancy conceived by assisted reproductive
      technology.
AB  - OBJECTIVE: Recent data suggest that singleton fetuses conceived by assisted
      reproductive technology (ART) present cardiovascular remodeling that may persist
      postnatally. Twin pregnancies are more frequent in the ART population and are
      associated with increased adverse perinatal outcomes, such as hypertensive
      disorders, gestational diabetes and preterm birth. However, it is unknown whether
      cardiac remodeling is also present in twin pregnancies conceived by ART. Our aim
      was to assess the presence of fetal cardiac remodeling and dysfunction in twin
      pregnancies conceived by ART as compared with those conceived spontaneously (SC).
      METHODS: This was a prospective cohort study including 50 dichorionic twin
      fetuses conceived by ART and 50 SC twin fetuses. The study protocol included
      collection of baseline/perinatal data and a fetal ultrasound examination at 28-30
      weeks' gestation, including assessment of estimated fetal weight, fetoplacental
      Doppler and fetal echocardiography. Measurements of atrial area, atrial/heart
      ratio, ventricular sphericity index, free wall thickness, mitral and tricuspid
      annular plane systolic excursions, and systolic and early diastolic peak
      velocities were assessed. Multilevel analyses were used to compare perinatal and
      ultrasonographic parameters. Comparisons of echocardiographic variables were
      adjusted for parental age, paternal body mass index and incidence of pre
      eclampsia. RESULTS: Compared with SC twins, ART twin fetuses showed significant
      cardiac changes, predominantly affecting the right heart, such as dilated atria
      (right atrial/heart area: 15.7 +/- 3.1 vs 18.4 +/- 3.2, P < 0.001), more globular
      ventricles (right ventricular sphericity index: 1.57 +/- 0.25 vs 1.41 +/- 0.23, P
      = 0.001) and thicker myocardial walls (septal wall thickness: 2.57 +/- 0.45 mm vs
      2.84 +/- 0.41 mm, P = 0.034) together with reduced longitudinal motion (tricuspid
      annular plane systolic excursion: 6.36 +/- 0.89 mm vs 5.18 +/- 0.93 mm, P <
      0.001). CONCLUSIONS: ART twin fetuses present signs of cardiac remodeling and
      dysfunction. These changes are similar to those observed in ART singletons and
      reinforce the concept of fetal cardiac programing in ART. These results open
      opportunities for early detection and intervention in infants conceived by ART.
      Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28508516
TI  - Fell Muir Lecture: Collagen fibril formation in vitro and in vivo.
AB  - It is a great honour to be awarded the Fell Muir Prize for 2016 by the British
      Society of Matrix Biology. As recipient of the prize, I am taking the opportunity
      to write a minireview on collagen fibrillogenesis, which has been the focus of my
      research for 33 years. This is the process by which triple helical collagen
      molecules assemble into centimetre-long fibrils in the extracellular matrix of
      animals. The fibrils appeared a billion years ago at the dawn of multicellular
      animal life as the primary scaffold for tissue morphogenesis. The fibrils occur
      in exquisite three-dimensional architectures that match the physical demands of
      tissues, for example orthogonal lattices in cornea, basket weaves in skin and
      blood vessels, and parallel bundles in tendon, ligament and nerves. The question
      of how collagen fibrils are formed was posed at the end of the nineteenth
      century. Since then, we have learned about the structure of DNA and the peptide
      bond, understood how plants capture the sun's energy, cloned animals, discovered
      antibiotics and found ways of editing our genome in the pursuit of new cures for
      diseases. However, how cells generate tissues from collagen fibrils remains one
      of the big unsolved mysteries in biology. In this review, I will give a personal
      account of the topic and highlight some of the approaches that my research group
      are taking to find new insights.

PMID- 28508520
TI  - Palladium(I) Dimer Enabled Extremely Rapid and Chemoselective Alkylation of Aryl
      Bromides over Triflates and Chlorides in Air.
AB  - Disclosed herein is the first general chemo- and site-selective alkylation of C
      Br bonds in the presence of COTf, C-Cl and other potentially reactive functional
      groups, using the air-, moisture-, and thermally stable dinuclear PdI catalyst,
      [Pd(MU-I)PtBu3 ]2 . The bromo-selectivity is independent of the substrate and the
      relative positioning of the competing reaction sites, and as such fully
      predictable. Primary and secondary alkyl chains were introduced with extremely
      high speed (<5 min reaction time) at room temperature and under open-flask
      reaction conditions.

PMID- 28508521
TI  - An Incidental Diffuse Midline Glioma Found at Autopsy.
AB  - This case shows an unexpected midline glioma found at autopsy. Two siblings were
      riding on a single bicycle on the side of a road. The 13-year-old brother was
      seated and steering the bicycle, while the 14-year-old sister held onto the back.
      The bicycle veered left into traffic and was struck by a vehicle. The siblings
      were admitted to the local Level 1 trauma center, but both later succumbed to
      injuries. Autopsies were performed on the children, including brains for
      neuropathologic evaluation. The brother was found to have an infiltrating
      astrocytoma located in the left middle cerebellar peduncle, with extension to the
      pons and medulla. His hospital course included several imaging studies using CT
      and MRI modalities. However, this lesion was not identified until the postmortem
      neuropathologic examination. This rare case shows the continued need for
      postmortem autopsy and the current limitations of medical imaging.

PMID- 28508522
TI  - In Situ Observation of Twin Boundary Sliding in Single Crystalline Cu Nanowires.
AB  - Using a homemade, novel, in situ transmission electron microscopy (TEM) double
      tilt tensile device, plastic behavior of single crystalline Cu nanowires of
      around 150 nm are studied. Deformation twins occur during the tests as
      predesigned before the experiments. In situ observation of twin boundary sliding
      (TBS) caused by full dislocation (extended dislocation) is first revealed at the
      atomic scale which is confirmed by molecular dynamics (MD) simulation results.
      Combined with twin boundary migration and multiple dislocations nucleated from
      surface, TBS causes a superlarge fracture strain which is over 166% and a severe
      necking which is over 93%, far beyond the typical values for most nanomaterials
      without twins.

PMID- 28508523
TI  - The effect of sodium hypochlorite concentration and irrigation needle extension
      on biofilm removal from a simulated root canal model.
AB  - To investigate the effect of sodium hypochlorite concentration and needle
      extension on removal of Enterococcus faecalis biofilm, sixty root canal models
      were 3D printed. Biofilms were grown on the apical 3 mm of the canal for 10 days.
      Irrigation for 60s with 9 mL of either 5.25% or 2.5% NaOCl or water was performed
      using a needle inserted either 3 or 2 mm from the canal terminus and imaged using
      fluorescence microscopy and residual biofilm percentages were calculated using
      imaging software. The data were analysed using analysis of covariance and two
      sample t-tests. A significance level of 0.05 was used throughout. Residual
      biofilm was less using 5.25% than with 2.5% NaOCl. Statistically significant
      biofilm removal was evident with the needle placed closer to the canal terminus.
      A greater reduction of available chlorine and pH was noted as the concentration
      increased. One-minute irrigation was not sufficient for complete biofilm removal.

PMID- 28508524
TI  - A Carbon Dioxide Bubble-Induced Vortex Triggers Co-Assembly of Nanotubes with
      Controlled Chirality.
AB  - It is challenging to prepare co-organized nanotube systems with controlled
      nanoscale chirality in an aqueous liquid flow field. Such systems are responsive
      to a bubbled external gas. A liquid vortex induced by bubbling carbon dioxide
      (CO2 ) gas was used to stimulate the formation of nanotubes with controlled
      chirality; two kinds of achiral cationic building blocks were co-assembled in
      aqueous solution. CO2 -triggered nanotube formation occurs by formation of
      metastable intermediate structures (short helical ribbons and short tubules) and
      by transition from short tubules to long tubules in response to chirality
      matching self-assembly. Interestingly, the chirality sign of these assemblies can
      be selected for by the circulation direction of the CO2 bubble-induced vortex
      during the co-assembly process.

PMID- 28508526
TI  - A complex case of ibrutinib treatment for a CLL patient on haemodialysis.

PMID- 28508525
TI  - The Structural Fate of Individual Multicomponent Metal-Oxide Nanoparticles in
      Polymer Nanoreactors.
AB  - Multicomponent nanoparticles can be synthesized with either homogeneous or phase
      segregated architectures depending on the synthesis conditions and elements
      incorporated. To understand the parameters that determine their structural fate,
      multicomponent metal-oxide nanoparticles consisting of combinations of Co, Ni,
      and Cu were synthesized by using scanning probe block copolymer lithography and
      characterized using correlated electron microscopy. These studies revealed that
      the miscibility, ratio of the metallic components, and the synthesis temperature
      determine the crystal structure and architecture of the nanoparticles. A Co-Ni-O
      system forms a rock salt structure largely owing to the miscibility of CoO and
      NiO, while Cu-Ni-O, which has large miscibility gaps, forms either homogeneous
      oxides, heterojunctions, or alloys depending on the annealing temperature and
      composition. Moreover, a higher-ordered structure, Co-Ni-Cu-O, was found to
      follow the behavior of lower ordered systems.

PMID- 28508527
TI  - Complete remission of primary cutaneous intravascular large B-cell lymphoma with
      R-CHOP followed by rituximab monotherapy.

PMID- 28508528
TI  - Competing-risks model in screening for pre-eclampsia in twin pregnancy by
      maternal characteristics and medical history.
AB  - OBJECTIVE: A survival-time regression model for gestational age at delivery with
      pre-eclampsia (PE) in singleton pregnancy, using maternal demographic
      characteristics and medical history, was reported previously. The objective of
      this study was to extend this model to dichorionic (DC) and monochorionic (MC)
      twin pregnancy. METHODS: The study population included 1789 DC and 430 MC twin
      pregnancies and 93 297 singleton pregnancies. A survival-time model for
      gestational age at delivery with PE was developed from variables of maternal
      characteristics and medical history. The risk of PE with delivery < 37 weeks and
      < 42 weeks in twin pregnancies was determined and compared with that in singleton
      pregnancies. RESULTS: In singleton pregnancies comprising women of Caucasian
      racial origin, mean weight of 69 kg at 12 weeks' gestation, mean height of 164
      cm, nulliparous, with spontaneous conception, no family history of PE and no
      history of diabetes mellitus, systemic lupus erythematosus or antiphospholipid
      syndrome, the mean of the Gaussian distribution of gestational age at delivery
      with PE was 55 weeks. In DC twins with PE, mean gestational age at delivery was
      shifted to the left by 8.2 (95% CI, 7.2-9.1) weeks and in MC twins it was shifted
      to the left by 10.0 (95% CI, 8.5-11.4) weeks. The risk of delivery with PE
      occurring at, or before, a specified gestational age is given by the area under
      the fitted distribution curve. For a reference population with the above
      characteristics, the estimated risk of PE < 37 weeks' gestation, assuming no
      other cause of delivery, was 0.6% for singletons, 9.0% for DC twins and 14.2% for
      MC twins; the respective values for PE < 42 weeks were 3.6%, 27.0% and 36.5%.
      CONCLUSIONS: A model based on maternal characteristics and medical history has
      been developed for estimation of patient-specific risks for PE in DC and MC twin
      pregnancy. Such estimation of the a-priori risk for PE is an essential first step
      in the use of Bayes' theorem to combine maternal factors with biomarkers for the
      continuing development of more effective methods of screening for the disease.
      Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28508529
TI  - Mastery Learning - does the method of learning make a difference in skills
      acquisition for robotic surgery?
AB  - BACKGROUND: Few studies compare the effectiveness of blocked vs random practice
      conditions in minimally invasive surgery training, and none have evaluated these
      in robotic surgery training. METHODS: The dV-Trainer(r) and the da Vinci(r)
      Surgical System (dVSS) were used to compare practice conditions. Forty-two
      participants were randomized into blocked and random practice groups. Each
      participant performed five tasks: Ring Walk, Thread the Rings, Needle Targeting,
      Suture Sponge and Tubes Level 2. Transfer to the dVSS was also assessed. RESULTS:
      No significant differences were observed between the two groups, except for a few
      instances. For example, during Ring Walk, the random group performed
      significantly faster than the blocked group (100.78 +/- 5.26 s vs 121.59 +/- 5.26
      s, p < 0.01). CONCLUSIONS: The study results do not follow the current evidence
      presented in the education literature. This is the first time that blocked versus
      random practice was tested for robotic surgery training.

PMID- 28508530
TI  - Seventeen-Coordinate Actinide Helium Complexes.
AB  - The geometries and electronic structures of molecular ions featuring He atoms
      complexed to actinide cations are explored computationally using density
      functional and coupled cluster theories. A new record coordination number is
      established, as AcHe173+ , ThHe174+ , and PaHe174+ are all found to be true
      geometric minima, with the He atoms clearly located in the first shell around the
      actinide. Analysis of AcHen3+ (n=1-17) using the quantum theory of atoms in
      molecules (QTAIM) confirms these systems as having closed shell, charge-induced
      dipole bonding. Excellent correlations (R2 >0.95) are found between QTAIM metrics
      (bond critical point electron densities and delocalization indices) and the
      average Ac-He distances, and also with the incremental He binding energies.

PMID- 28508531
TI  - Avoiding experimental death: the EQUATOR network (a valuable resource for
      research).

PMID- 28508532
TI  - Aortic valve replacement for papillary fibroelastoma.
AB  - Surgery is indicated for symptomatic patients with papillary fibroelastomas (PFE)
      on the aortic valve. The valve is commonly spared during tumor excision. Rarely,
      aortic valve replacement (AVR) is needed. We present a case requiring AVR for an
      aortic valve PFE and review the literature to determine the risk factors for
      failure of aortic valve-sparing techniques in patients with PFE.

PMID- 28508533
TI  - Intermolecular Charge-Transfer Interactions Facilitate Two-Photon Absorption in
      Styrylpyridine-Tetracyanobenzene Cocrystals.
AB  - Cocrystals of 4-styrylpyridine and 1,2,4,5-tetracyanobenzene were successfully
      prepared by supramolecular self-assembly. Donor-acceptor interactions between the
      molecular components are the main driving force for self-assembly and contribute
      to intermolecular charge transfer. The cocrystals possess two-photon absorption
      properties that are not observed in the individual components; suggesting that
      two-photon absorption originates from intermolecular charge-transfer interactions
      in the donor-acceptor system. The origin of two-photon absorption in
      multichromophore systems remains under-researched; thus, the system offers a rare
      demonstration of two-photon absorption by cocrystallization. Cocrystal
      engineering may facilitate further design and development of novel materials for
      nonlinear optical and optoelectronic applications.

PMID- 28508534
TI  - Large-Scale Suspended Graphene Used as a Transparent Substrate for Infrared
      Spectroscopy.
AB  - Due to weak interactions between micrometer-wavelength infrared (IR) light and
      nanosized samples, a high signal to noise ratio is a prerequisite in order to
      precisely characterize nanosized samples using IR spectroscopy. Traditional
      micrometer-thick window substrates, however, have considerable IR absorption
      which may introduce unavoidable deformations and interruptions to IR spectra of
      nanoscale samples. A promising alternative is the use of a suspended graphene
      substrate which has ultrahigh IR transmittance (>97.5%) as well as unique
      mechanical properties. Here, an effective method is presented for fabrication of
      suspended graphene over circular holes up to 150 um in diameter to be utilized as
      a transparent substrate for IR spectroscopy. It is demonstrated that the
      suspended graphene has little impact on the measured IR spectra, an advantage
      which has led to the discovery of several missing vibrational modes of a 20 nm
      thick PEO film measured on a traditional CaF2 substrate. This can provide a
      better understanding of molecules' fine structures and status of hanging bands.
      The unique optical properties of suspended graphene are determined to be superior
      to those of conventional IR window materials, giving this new substrate great
      potential as part of a new generation of IR transparent substrates, especially
      for use in examining nanoscale samples.

PMID- 28508535
TI  - Costimulation Blockade: America First, Canada Second ... What About Norway?

PMID- 28508536
TI  - Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis.

PMID- 28508537
TI  - Superorganismality and caste differentiation as points of no return: how the
      major evolutionary transitions were lost in translation.
AB  - More than a century ago, William Morton Wheeler proposed that social insect
      colonies can be regarded as superorganisms when they have morphologically
      differentiated reproductive and nursing castes that are analogous to the metazoan
      germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's
      insights were largely neglected, and we were left with multiple new superorganism
      concepts that are mutually inconsistent and uninformative on how
      superorganismality originated. These difficulties can be traced to the broadened
      sociobiological concept of eusociality, which denies that physical queen-worker
      caste differentiation is a universal hallmark of superorganismal colonies. Unlike
      early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher
      and Haldane, who set out to explain the acquisition of an unmated worker caste,
      the goal of sociobiology was to understand the evolution of eusociality, a broad
      brush convenience category that covers most forms of cooperative breeding. By
      lumping a diverse spectrum of social systems into a single category, and drawing
      attention away from the evolution of distinct quantifiable traits, the
      sociobiological tradition has impeded straightforward connections between
      inclusive fitness theory and the major evolutionary transitions paradigm for
      understanding irreversible shifts to higher organizational complexity. We
      evaluate the history by which these inconsistencies accumulated, develop a common
      cause approach for understanding the origins of all major transitions in
      eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are
      directly comparable. We show that only Wheeler's original definition of
      superorganismality can be unambiguously linked to irreversible evolutionary
      transitions from context-dependent reproductive altruism to unconditional
      differentiation of permanently unmated castes in the ants, corbiculate bees,
      vespine wasps and higher termites. We argue that strictly monogamous parents were
      a necessary, albeit not sufficient condition for all transitions to
      superorganismality, analogous to single-zygote bottlenecking being a necessary
      but not sufficient condition for the convergent origins of complex soma across
      multicellular eukaryotes. We infer that conflict reduction was not a necessary
      condition for the origin of any of these major transitions, and conclude that
      controversies over the status of inclusive fitness theory primarily emanate from
      the arbitrarily defined sociobiological concepts of superorganismality and
      eusociality, not from the theory itself.

PMID- 28508539
TI  - The effect of maternal obesity on fatty acid transporter expression and lipid
      metabolism in the full-term placenta of lean breed swine.
AB  - This study was conducted to evaluate the influence of back-fat thickness (BF), at
      mating of sows, on the maternal and newborn circulating lipids, expression of
      placental fatty acids (FA) transporters and lipid accumulation in placenta. Full
      term placentas were obtained by vaginal delivery from BFI (9-14 mm; n = 37), BFII
      (15-19 mm; n = 43) and BFIII (20-27 mm; n = 38) sows according to BF at mating,
      and frozen placental sections were analysed for fat accumulation. Blood samples
      were collected from the sows of day 105 pregnancy and from cord blood at
      delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR
      and Western blotting. Our results demonstrated that BFII females had
      significantly increased litter weight and placental efficiency, decreased
      maternal triglyceride (TG) and non-esterified fatty acids (NEFA) levels,
      decreased maternal IL-6, TNFalpha and leptin levels compared to BFIII females (p
      < .05). BFIII sows were associated with significantly decreased newborn TG
      levels, increased newborn glucose, IL-6 and TNFalpha levels compared to BFI or
      BFII sows (p < .05). BFI and BFII females had significantly decreased placental
      TG, NEFA and cholesterol (CHOL) contents compared to BFIII females (p < .05).
      Moreover, decreased CD36, FATP1, FABP4, and FABP1 mRNA and protein and FATP4
      protein expression, and increased LPL activity were also observed in BFIII group
      compared with BFII group (p < .05). PPARgamma mRNA and protein and lipogenic
      genes such as SREBP-1c, ACSL1, ACCalpha, FAS and SCD mRNA expression were
      downregulated or upregulated, respectively, in the placentas of BFIII sows
      compared to BFI or BFII sows (p < .05). Overall, this study demonstrated that
      there is no advantage, in terms of litter live size, litter weight and placental
      FA transport and metabolism, in performing the mating of sows with BF>19 mm.

PMID- 28508538
TI  - Prognostic Value of Predialysis Indices for Technique Failure and Mortality in
      Peritoneal Dialysis Patients.
AB  - Technique failure remains a frequent cause of peritoneal dialysis (PD)
      withdrawal. Many post-commencement predictors of PD technique failure have been
      identified, while predialysis predictors have remained unclear. The aim of this
      study was to identify predialysis indices for technique failure in PD patients.
      We recruited 206 consecutive PD patients who were treated at Nara Medical
      University Hospital between 1 April 1997 and 31 December 2012. Forty-eight
      patients were excluded because of transition from hemodialysis (HD) or withdrawal
      from PD within 3 months, leaving 158 patients for analysis. Clinical
      characteristics and laboratory data from within 3 months preceding PD
      commencement were analyzed. The primary outcome was the composite of time to
      combined use of HD, transition to HD, and all-cause mortality within 2 years
      after PD commencement. During the study period, the primary outcome was observed
      in 50 patients. Using multivariate analysis, greater age (odds ratios (ORs)
      [95%CI], 3.08 [1.72-5.61]), anemia (ORs [95%CI], 2.12 [1.08-4.43]),
      overweight/obesity (ORs [95%CI], 2.09 [1.16-3.72]), and hypocalcemia (ORs
      [95%CI], 1.86 [1.04-3.35]) were independently associated with technique failure.
      Adding corrected calcium to the model incorporating age, body mass index, and
      hemoglobin significantly increased the c-statistic from 0.678 to 0.755 (P =
      0.048) relative to the model incorporating age alone. The integrated
      discrimination improvement was 0.085 (95% CI 0.036-0.134, P < 0.001) and the
      continuous net reclassification improvement was 0.395 (95% CI 0.066-0.724, P =
      0.02). In conclusion, the combination of predialysis indices comprising age,
      overweight/obesity, anemia, and corrected calcium could provide a significant
      predictive value for technique failure of PD.

PMID- 28508540
TI  - Recurrent fetal thyrotoxicosis in woman with history of Hashimoto's thyroiditis.

PMID- 28508541
TI  - Opt-in or opt-out to increase organ donation in South Africa? Appraising proposed
      strategies using an empirical ethics analysis.
AB  - Utilising empirical ethics analysis, we evaluate the merits of systems proposed
      to increase deceased organ donation in South Africa (SA). We conclude that SA
      should maintain its soft opt-in policy, and enhance it with 'required transplant
      referral' in order to maximise donor numbers within an ethically and legally
      acceptable framework. In SA, as is the case worldwide, the demand for donor
      organs far exceeds the supply thereof. Currently utilising a soft opt-in system,
      SA faces the challenge of how to increase donor numbers in a context which is
      imbued with inequalities in access to healthcare, multiplicitous personal beliefs
      and practices, distrust of organ transplant and varying levels of education and
      health literacy. We argue that a hard opt-in, opt-out or mandated consent system
      would be problematic, and we present empirical data from Gauteng Province
      illustrating barriers to ethically sound practice in soft consent systems.
      Ultimately, we argue that in spite of some limitations, a soft opt-in system is
      most realistic for SA because its implementation does not require extensive
      public education campaigns at national level, and it does not threaten to further
      erode trust at a clinical level. However, to circumvent some of the clinical
      level barriers identified in our empirical study, we propose a contextually
      sensitive option for "enabling" soft opt-in through "required transplant
      referral". We argue that this system is legally defensible, enhances ethical
      practice and could also increase donor numbers as it has in many other countries.

PMID- 28508542
TI  - Dynamic Self-Assembly of Homogenous Microcyclic Structures Controlled by a Silver
      Coated Nanopore.
AB  - The self-assembly of nanoparticles is a challenging process for organizing
      precise structures with complicated and ingenious structures. In the past
      decades, a simple, high-efficiency, and reproducible self-assembly method from
      nanoscale to microscale has been pursued because of the promising and extensive
      application prospects in bioanalysis, catalysis, photonics, and energy storage.
      However, microscale self-assembly still faces big challenges including improving
      the stability and homogeneity as well as pursuing new assembly methods and
      templates for the uniform self-assembly. To address these obstacles, here, a
      novel silver-coated nanopore is developed which serves as a template for
      electrochemically generating microcyclic structures of gold nanoparticles at
      micrometers with highly homogenous size and remarkable reproducibility. Nanopore
      induced microcyclic structures are further applied to visualize the diffusion
      profile of ionic flux. Based on this novel strategy, a nanopore could potentially
      facilitate the delivery of assembled structures for many practical applications
      including drug delivery, cellular detection, catalysis, and plasmonic sensing.

PMID- 28508543
TI  - True Transsphenoidal Meningoencephalocele.

PMID- 28508544
TI  - A Decision Tree for Nonmetric Sex Assessment from the Skull.
AB  - This study uses five well-documented cranial nonmetric traits (glabella, mastoid
      process, mental eminence, supraorbital margin, and nuchal crest) and one
      additional trait (zygomatic extension) to develop a validated decision tree for
      sex assessment. The decision tree was built and cross-validated on a sample of
      293 U.S. White individuals from the William M. Bass Donated Skeletal Collection.
      Ordinal scores from the six traits were analyzed using the partition modeling
      option in JMP Pro 12. A holdout sample of 50 skulls was used to test the model.
      The most accurate decision tree includes three variables: glabella, zygomatic
      extension, and mastoid process. This decision tree yielded 93.5% accuracy on the
      training sample, 94% on the cross-validated sample, and 96% on a holdout
      validation sample. Linear weighted kappa statistics indicate acceptable agreement
      among observers for these variables. Mental eminence should be avoided, and
      definitions and figures should be referenced carefully to score nonmetric traits.

PMID- 28508545
TI  - Comparison of joint modeling and landmarking for dynamic prediction under an
      illness-death model.
AB  - Dynamic prediction incorporates time-dependent marker information accrued during
      follow-up to improve personalized survival prediction probabilities. At any
      follow-up, or "landmark", time, the residual time distribution for an individual,
      conditional on their updated marker values, can be used to produce a dynamic
      prediction. To satisfy a consistency condition that links dynamic predictions at
      different time points, the residual time distribution must follow from a
      prediction function that models the joint distribution of the marker process and
      time to failure, such as a joint model. To circumvent the assumptions and
      computational burden associated with a joint model, approximate methods for
      dynamic prediction have been proposed. One such method is landmarking, which fits
      a Cox model at a sequence of landmark times, and thus is not a comprehensive
      probability model of the marker process and the event time. Considering an
      illness-death model, we derive the residual time distribution and demonstrate
      that the structure of the Cox model baseline hazard and covariate effects under
      the landmarking approach do not have simple form. We suggest some extensions of
      the landmark Cox model that should provide a better approximation. We compare the
      performance of the landmark models with joint models using simulation studies and
      cognitive aging data from the PAQUID study. We examine the predicted
      probabilities produced under both methods using data from a prostate cancer
      study, where metastatic clinical failure is a time-dependent covariate for
      predicting death following radiation therapy.

PMID- 28508546
TI  - Necrolytic migratory erythema associated with glucagonoma treated successfully
      with cyclosporine.

PMID- 28508547
TI  - Functional phosphatome requirement for protein homeostasis, networked
      mitochondria, and sarcomere structure in C. elegans muscle.
AB  - BACKGROUND: Skeletal muscle is central to locomotion and metabolic homeostasis.
      The laboratory worm Caenorhabditis elegans has been developed into a genomic
      model for assessing the genes and signals that regulate muscle development and
      protein degradation. Past work has identified a receptor tyrosine kinase
      signalling network that combinatorially controls autophagy, nerve signal to
      muscle to oppose proteasome-based degradation, and extracellular matrix-based
      signals that control calpain and caspase activation. The last two discoveries
      were enabled by following up results from a functional genomic screen of known
      regulators of muscle. Recently, a screen of the kinome requirement for muscle
      homeostasis identified roughly 40% of kinases as required for C. elegans muscle
      health; 80 have identified human orthologues and 53 are known to be expressed in
      skeletal muscle. To complement this kinome screen, here, we screen most of the
      phosphatases in C. elegans. METHODS: RNA interference was used to knockdown
      phosphatase-encoding genes. Knockdown was first conducted during development with
      positive results also knocked down only in fully developed adult muscle. Protein
      homeostasis, mitochondrial structure, and sarcomere structure were assessed using
      transgenic reporter proteins. Genes identified as being required to prevent
      protein degradation were also knocked down in conditions that blocked proteasome
      or autophagic degradation. Genes identified as being required to prevent
      autophagic degradation were also assessed for autophagic vesicle accumulation
      using another transgenic reporter. Lastly, bioinformatics were used to look for
      overlap between kinases and phosphatases required for muscle homeostasis, and the
      prediction that one phosphatase was required to prevent mitogen-activated protein
      kinase activation was assessed by western blot. RESULTS: A little over half of
      all phosphatases are each required to prevent abnormal development or maintenance
      of muscle. Eighty-six of these phosphatases have known human orthologues, 57 of
      which are known to be expressed in human skeletal muscle. Of the phosphatases
      required to prevent abnormal muscle protein degradation, roughly half are
      required to prevent increased autophagy. CONCLUSIONS: A significant portion of
      both the kinome and phosphatome are required for establishing and maintaining C.
      elegans muscle health. Autophagy appears to be the most commonly triggered form
      of protein degradation in response to disruption of phosphorylation-based
      signalling. The results from these screens provide measurable phenotypes for
      analysing the combined contribution of kinases and phosphatases in a multi
      cellular organism and suggest new potential regulators of human skeletal muscle
      for further analysis.

PMID- 28508548
TI  - A prospective evaluation of methylene blue and gentian violet dressing for
      management of chronic wounds with local infection.
AB  - The objective of this prospective, non-randomised study was to evaluate the
      performance of an antibacterial foam dressing containing methylene blue and
      gentian violet (Hydrofera Blue Classic dressing(r) ) for the management of
      chronic wounds with local infection. Patients in this study were >=18 years of
      age (n = 29), and each had at least one chronic wound >=1 cm2 in size that showed
      signs of localised infection or critical colonisation but with good potential for
      healing based on clinical assessment. To all of these wounds, the dressing was
      applied and changed three times per week over the 4-week study period. The
      primary endpoints of the study were: (i) changes in wound surface area
      measurement, (ii) changes in Pressure Ulcer Scale for Healing (PUSH) scores,
      (iii) changes in percent surface area of devitalised tissue (i.e., yellow slough
      or other necrotic tissue) and (iv) changes in clinical signs associated with
      localised wound infection/critical colonisation. Participants were evaluated at
      presentation (week 0 = baseline), week 2 and at week 4 (end of the study). The 29
      patients completed the study, and at week 4, the following wound improvements
      were observed: (i) baseline mean wound surface area was significantly reduced by
      42.5%, from 21.4 to 12.3 cm2 at week 4 (P = 0.005); (ii) baseline mean PUSH score
      decreased significantly from 13.3 to 10.7 at week 4 (P < 0.001); (iii) baseline
      mean wound coverage by devitalised tissue (%) was significantly reduced, from
      52.6 % to 11.4% at week 4 (P < 0.001) and (iv) the mean UPPER and LOWER wound
      infection scores were reduced from 3.6 at baseline to 0.9 at week 4 (75%; P <
      0.001). These results indicate that the Hydrofera Blue Classic dressing was
      effective at managing these chronic wounds and helped them progress onto a
      healing trajectory.

PMID- 28508549
TI  - Prenatal prediction of postnatal large-for-dates neonates using a simplified MRI
      method: comparison with conventional 2D ultrasound estimates.
AB  - OBJECTIVE: To evaluate the performance of a simple semi-automated method for
      estimation of fetal weight (EFW) using magnetic resonance imaging (MRI) as
      compared with two-dimensional (2D) ultrasound (US) for the prediction of large
      for-dates neonates. METHODS: Data of two groups of women with singleton pregnancy
      between March 2011 and May 2016 were retrieved from our database and evaluated
      retrospectively: the first group included women who underwent US-EFW and MRI-EFW
      within 48 h before delivery and the second group included women who had these
      evaluations between 35 + 0 weeks and 37 + 6 weeks of gestation, more than 48 h
      before delivery. US-EFW was based on Hadlock et al. and MRI-EFW on the formula
      described by Baker et al. For MRI-EFW, planimetric measurement of the fetal body
      volume (FBV) was performed using a semi-automated method and the time required
      for measurement was noted. Outcome measure was the performance of MRI-EFW vs US
      EFW in the prediction of large-for-dates neonates, both <= 48 h and > 48 h before
      delivery. Receiver-operating characteristics (ROC) curves for each method were
      compared using the DeLong method. RESULTS: Of the 270 women included in the first
      group, 48 (17.8%) newborns had birth weight >= 90th centile and 30 (11.1%) >=
      95th centile. The second group included 83 women, and nine (10.8%) newborns had
      birth weight >= 95th centile. Median time needed for FBV planimetric measurements
      in all 353 fetuses was 3.5 (range, 1.5-5.5) min. The area under the ROC curve
      (AUC) for prediction of large-for-dates neonates by prenatal MRI performed within
      48 h before delivery was significantly higher than that by US (for birth weight
      >= 90th centile, difference between AUCs = 0.085, standard error (SE) = 0.020, P
      < 0.001; for birth weight >= 95th centile, difference between AUCs = 0.036, SE =
      0.014, P = 0.01). Similarly, MRI-EFW was better than US-EFW in predicting birth
      weight >= 95th centile when both examinations were performed > 48 h prior to
      delivery (difference between AUCs = 0.077, SE = 0.039, P = 0.045). CONCLUSION:
      MRI planimetry using our purpose-designed semi-automated method is not time
      consuming. The predictive performance of MRI-EFW performed immediately prior to
      or remote from delivery is significantly better than that of US-EFW for the
      prediction of large-for-dates neonates. Copyright (c) 2017 ISUOG. Published by
      John Wiley & Sons Ltd.

PMID- 28508550
TI  - Photoluminescent Peptide-Based Nanostructures as FRET Donor for Fluorophore Dye.
AB  - A great interest has been recently generated by the discovery that peptide-based
      nanostructures (NSs) endowed with cross-beta structure may show interesting
      photoluminescent (PL) properties. It was shown that NSs formed by PEGylated
      hexaphenylalanine (PEG8 -F6, PEG=polyethylene glycol) are able to emit at 460 nm
      when excited at 370 or 410 nm. Here, the possibility to transfer the fluorescence
      of these PEG8 -F6-based NSs by foster resonance electron transfer (FRET)
      phenomenon to a fluorescent dye was explored. To achieve this aim, the 4-chloro-7
      nitrobenzofurazan (NBD) dye was encapsulated in these NSs. Structural data in
      solution and in solid state, obtained by a variety of techniques (circular
      dichroism, Fourier-transform infrared spectroscopy, wide-angle X-ray scattering,
      and small-angle X-ray scattering), indicated that the organization of the peptide
      spine of PEG8 -F6 NS, which consists of anti-parallel beta-sheets separated by a
      dry interface made of interacting phenylalanine side chains, was maintained upon
      NBD encapsulation. The spectroscopic characterization of these NSs clearly showed
      a red-shift of the emission fluorescence peak both in solution and in solid
      state. This shift from 460 to 530 nm indicated that a FRET phenomenon from the
      peptide-based to the fluorophore-encapsulated NS occurred. FRET could also be
      detected in the PEG8 -F6 conjugate, in which the NBD was covalently bound to the
      amine of the compound. On the basis of these results, it is suggested that the
      red-shift of the intrinsic PL of NSs may be exploited in the bio-imaging field.

PMID- 28508551
TI  - First study of mtDNA (D-loop) in Brazilian Caipira chickens.

PMID- 28508552
TI  - Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using
      Dissolution DNP NMR Spectroscopy.
AB  - The kinase inhibitory domain of the cell cycle regulatory protein p27Kip1 (p27)
      was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D
      DNP). While intrinsically disordered in isolation, p27 adopts secondary
      structural motifs, including an alpha-helical structure, upon binding to cyclin
      dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with
      hyperpolarization enable the real-time observation of 13 C NMR signals during p27
      folding upon binding to Cdk2/cyclin A on a time scale of several seconds. Time
      dependent intensity changes are dependent on the extent of folding and binding,
      as manifested in differential spin relaxation. The analysis of signal decay rates
      suggests the existence of a partially folded p27 intermediate during the
      timescale of the D-DNP NMR experiment.

PMID- 28508555
TI  - Laminin and collagen IV inclusion in immunoisolating microcapsules reduces
      cytokine-mediated cell death in human pancreatic islets.
AB  - Extracellular matrix (ECM) molecules have several functions in pancreatic islets,
      including provision of mechanical support and prevention of cytotoxicity during
      inflammation. During islet isolation, ECM connections are damaged, and are not
      restored after encapsulation and transplantation. Inclusion of specific
      combinations of collagen type IV and laminins in immunoisolating capsules can
      enhance survival of pancreatic islets. Here we investigated whether ECM can also
      enhance survival and lower susceptibility of human islets to cytokine-mediated
      cytotoxicity. To this end, human islets were encapsulated in alginate with
      collagen IV and either RGD, LRE or PDSGR, i.e. laminin sequences. Islets in
      capsules without ECM served as control. The encapsulated islets were exposed to
      IL-1beta, IFN-gamma and TNF-alpha for 24 and 72 h. All combinations of ECM
      improved the islet cell survival, and reduced necrosis and apoptosis after
      cytokine exposure (P < 0.01). Collagen IV-RGD and collagen IV-LRE reduced danger
      associated molecular patterns (DAMPs) release from islets (P < 0.05). Moreover,
      collagen IV-RGD and collagen IV-PDSGR, but not collagen IV-LRE, reduced NO
      release from encapsulated human islets (P < 0.05). This reduction correlated with
      a higher oxygen consumption rate (OCR) of islets in capsules containing collagen
      IV-RGD and collagen IV-PDSGR. Islets in capsules with collagen IV-LRE showed more
      dysfunction, and OCR was not different from islets in control capsules without
      ECM. Our study demonstrates that incorporation of specific ECM molecules such as
      collagen type IV with the laminin sequences RGD and PDSGR in immunoisolated
      islets can protect against cytokine toxicity.

PMID- 28508553
TI  - A targeted proteomic assay for the measurement of plasma proteoforms related to
      human aging phenotypes.
AB  - Circulating polypeptides and proteins have been implicated in reversing or
      accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8),
      GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein
      products arising from a single gene due to alternative splicing and PTMs, have
      been challenging to study. Both GDF8 and GDF11 have known antagonists such as
      follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain
      containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed
      SRM assay using LC-MS/MS to measure five proteins related to GDF8 and GDF11
      signaling, and in addition, eotaxin, and oxytocin. Eighteen peptides consisting
      of 54 transitions were monitored and validated in pooled human plasma. In 24
      adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide,
      11.0 (2.4); GDF8 mature protein, 25.7 (8.0); GDF11 propeptide, 21.3 (10.9); GDF11
      mature protein, 16.5 (12.4); FST, 29.8 (7.1); FST cleavage form FST303, 96.4
      (69.2); WFIKKN1, 38.3 (8.3); WFIKKN2, 32.2 (10.5); oxytocin, 1.9 (0.9); and
      eotaxin, 2.3 (0.5). This novel multiplexed SRM assay should facilitate the study
      of the relationships of these proteoforms with major aging phenotypes.

PMID- 28508554
TI  - Intestinal epithelial suppressor of cytokine signaling 3 (SOCS3) impacts on
      mucosal homeostasis in a model of chronic inflammation.
AB  - INTRODUCTION: Suppressor of cytokine signaling 3 (SOCS3) is a tumour suppressor,
      limiting intestinal epithelial cell (IEC) proliferation in acute inflammation,
      and tumour growth, but little is known regarding its role in mucosal homeostasis.
      Resistance to the intestinal helminth Trichuris muris relies on an "epithelial
      escalator" to expel the parasite. IEC turnover is restricted by parasite-induced
      indoleamine 2,3-dioxygenase (IDO). METHODS: Mice with or without conditional
      knockout of SOCS3 were infected with T. muris. Crypt depth, worm burden, and
      proliferating cells and IDO were quantified. SOCS3 knockdown was also performed
      in human IEC cell lines. RESULTS: Chronic T. muris infection increased expression
      of SOCS3 in wild-type mice. Lack of IEC SOCS3 led to a modest increase in
      epithelial turnover. This translated to a lower worm burden, but not complete
      elimination of the parasite suggesting a compensatory mechanism, possibly IDO, as
      seen in SOCS3 knockdown. CONCLUSIONS: We report that SOCS3 impacts on IEC
      turnover following T. muris infection, potentially through enhancement of IDO.
      IDO may dampen the immune response which can drive IEC hyperproliferation in the
      absence of SOCS3, demonstrating the intricate interplay of immune signals
      regulating mucosal homeostasis, and suggesting a novel tumour suppressor role of
      SOCS3.

PMID- 28508556
TI  - Impact of co-morbidities on resource use and adherence to guidelines among
      commercially insured adults with new visits for back pain.
AB  - RATIONALE, AIMS AND OBJECTIVES: To assess if co-morbidity is associated with
      higher use of back-related care and adherence to back pain guidelines. METHODS:
      We conducted a retrospective cohort study using administrative claims data from
      2007-2011. We included individuals >=18 years with an index visit for back pain.
      Co-morbidities were measured 12 months prior to index. Co-morbidity burden was
      measured using Quan's Co-morbidity Index. Co-morbidities categories were measured
      using chronic condition indicators from the Agency for Healthcare Research and
      Quality. Total lumbar spine-related resource use for three years was ascertained
      using procedure codes. A clustering algorithm identified higher long-term
      utilizer. We identified initial use from day 0-42 for several categories of spine
      related care. We used logistic regression to test the association between co
      morbidities and resource use. RESULTS: Greater co-morbidity burden was associated
      with higher long-term spine-related resource use. Those with >=2 on Quan's Co
      morbidity Index had 29% higher odds of being a high back-specific resource user
      compared to those with no co-morbidities [Odds Ratio (OR): 1.29, 95% Confidence
      Interval (CI): 1.23-1.35]. Greater co-morbidity burden was associated with more
      frequent initial use of imaging, emergency visits, injections, and opioid fills;
      and less frequent initial use of medical and physical therapy visits. Co-morbid
      musculoskeletal conditions had the strongest association with being a high
      utilizer of long-term back-specific resources (OR: 1.53, 95% CI: 1.50-1.57).
      CONCLUSIONS: Co-morbidity burden and the presence of specific chronic conditions,
      such as musculoskeletal conditions, were associated with high long-term use of
      back-related care and care inconsistent with guidelines.

PMID- 28508557
TI  - LOPP chemotherapy as a first-line treatment for dogs with T-cell lymphoma.
AB  - BACKGROUND: The aim of this study was to describe the use of a lomustine (CCNU),
      vincristine, procarbazine and prednisolone (LOPP) protocol used for treatment of
      chemotherapy naive T-cell lymphoma patients and to describe the response rate,
      toxicity and disease-free interval compared historically to CHOP chemotherapy.
      MATERIALS AND METHODS: Retrospective case study of 31 dogs with naive T-cell
      lymphoma treated with a lomustine (CCNU), vincristine, procarbazine and
      prednisolone (LOPP) protocol. RESULTS: Thirty-one dogs with T cell lymphoma were
      treated. The overall response rate was 97%. Of the 30 dogs that had a response to
      LOPP chemotherapy, the median disease free interval was 176 days (range 0-1745
      days). The median overall survival time for this study group was 323 days (range
      51-1758 days). All deaths in this study were attributable to lymphoma.
      CONCLUSION: LOPP chemotherapy for T cell lymphoma is well tolerated with a low
      toxicity profile and an excellent overall response rate. This protocol showed
      minimal toxicity and comparable disease free interval and survival times for
      canine high grade T cell lymphoma treated with CHOP.

PMID- 28508558
TI  - Individual survival curves comparing subjective and observed mortality risks.
AB  - We compare individual survival curves constructed from objective (actual
      mortality) and elicited subjective information (probability of survival to a
      given target age). We develop a methodology to estimate jointly subjective and
      objective individual survival curves accounting for rounding on subjective
      reports of perceived survival. We make use of the long follow-up period in the
      Health and Retirement Study and the high quality of mortality data to estimate
      individual survival curves that feature both observed and unobserved
      heterogeneity. This allows us to compare objective and subjective estimates of
      remaining life expectancy for various groups and compare welfare effects of
      objective and subjective mortality risk using the life cycle model of
      consumption. We find that subjective and objective hazards are not the same. The
      median welfare loss from misperceptions of mortality risk when annuities are not
      available is 7% of current wealth at age 65 whereas more than 25% of respondents
      have losses larger than 60% of wealth. When annuities are available and
      exogenously given, the welfare loss is substantially lower.

PMID- 28508559
TI  - Two weeks of repetitive gut-challenge reduce exercise-associated gastrointestinal
      symptoms and malabsorption.
AB  - Debilitating gastrointestinal symptoms is a common feature of endurance running
      and may be exacerbated by and/or limit the ability to tolerate carbohydrate
      intake during exercise. The study aimed to determine whether two weeks of
      repetitive gut-challenge during running can reduce exercise-associated
      gastrointestinal symptoms and carbohydrate malabsorption. Endurance runners
      (n=18) performed an initial gut-challenge trial (GC1) comprising 2-hour running
      exercise at 60% VO2max (steady state) while consuming a formulated gel-disk
      containing 30 g carbohydrates (2:1 glucose-fructose, 10% w/v) every 20 minutes,
      followed by a 1-hour running effort bout. Gastrointestinal symptoms, feeding
      tolerance, and breath hydrogen (H2 ) were determined along the gut-challenge
      trial. After GC1, participants were randomly assigned to a blinded carbohydrate
      (CHO, 90 gCHO hour-1 ) or placebo (PLA, 0 gCHO hour-1 ) gut-training group. This
      comprised of consuming the group-specific feeding intervention during 1-hour
      running exercise at 60% VO2max equivalent, daily over a period of two weeks.
      Participants then repeated the gut-challenge trial (GC2). In GC2, a reduced gut
      discomfort (P=.012), total (P=.009), upper- (P=.015), and lower-gastrointestinal
      (P=.008) symptoms, and nausea (P=.05) were observed on CHO, but not PLA. Feeding
      tolerance did not differ between GC1 and GC2 on CHO and PLA. H2 peak was
      attenuated in GC2 (6+/-3 ppm) compared to GC1 (13+/-6 ppm) on CHO (P=.004), but
      not on PLA (GC1 11+/-7 ppm, and GC2 10+/-10 ppm). The effort bout distance was
      greater in GC2 (12.3+/-1.3 km) compared with GC1 (11.7+/-1.5 km) on CHO (P=.035)
      only. Two weeks of repetitive gut-challenge improve gastrointestinal symptoms and
      reduce carbohydrate malabsorption during endurance running, which may have
      performance implications.

PMID- 28508560
TI  - Anionic Regulated NiFe (Oxy)Sulfide Electrocatalysts for Water Oxidation.
AB  - The construction of active sites with intrinsic oxygen evolution reaction (OER)
      is of great significance to overcome the limited efficiency of abundant
      sustainable energy devices such as fuel cells, rechargeable metal-air batteries,
      and in water splitting. Anionic regulation of electrocatalysts by modulating the
      electronic structure of active sites significantly promotes OER performance. To
      prove the concept, NiFeS electrocatalysts are fabricated with gradual variation
      of atomic ratio of S:O. With the rise of S content, the overpotential for water
      oxidation exhibits a volcano plot under anionic regulation. The optimized NiFeS-2
      electrocatalyst under anionic regulation possesses the lowest OER overpotential
      of 286 mV at 10 mA cm-2 and the fastest kinetics being 56.3 mV dec-1 to date. The
      anionic regulation methodology not only serves as an effective strategy to
      construct superb OER electrocatalysts, but also enlightens a new point of view
      for the in-depth understanding of electrocatalysis at the electronic and atomic
      level.

PMID- 28508561
TI  - Diclofenac for pain associated with intravitreal injections: a prospective,
      randomized, placebo-controlled study.
AB  - IMPORTANCE: Intravitreal injections (IVI) are often painful. BACKGROUND: To
      evaluate the analgesic effect of diclofenac in patients undergoing IVI. DESIGN:
      Single-centre, prospective, randomized, triple-arm, placebo-controlled,
      interventional study in the University Hospital of Patras. PARTICIPANTS: Seventy
      four patients. METHODS: Group 1 (n = 25) received topical diclofenac 45 min
      before IVI, Group 2 (n = 25) received oral diclofenac 4 h before IVI and topical
      diclofenac while Group 3 (n = 24) received placebo before IVI. Using the short
      form of the McGill Pain Questionnaire (SF-MPQ), pain intensity was assessed with
      the visual analogue scale (VAS), the main component of the SF-MPQ and the Present
      Pain Intensity (PPI) scores immediately and 6 h post-IVI. MAIN OUTCOME MEASURES:
      The VAS pain score immediately post-IVI. RESULTS: Immediately post-IVI, patients
      in Group 2 reported significantly lower VAS pain scores compared to placebo while
      no statistically significant difference was found between patients that received
      topical diclofenac and placebo. Six hours post-IVI, patients in both treatment
      groups reported significant lower VAS pain scores compared to placebo. The scores
      of the main component of the SF-MPQ were significantly lower in patients of
      treatment groups compared to placebo at both time-points. Finally, while no
      statistically significant difference was found between the 3 Groups in PPI scores
      immediately post-IVI, 6 h later, patients of both treatment groups reported
      significantly lower PPI scores compared to placebo. CONCLUSIONS AND RELEVANCE:
      The combination of topical and oral diclofenac demonstrated better analgesic
      effect than topical diclofenac administration in patients undergoing IVI
      immediately and up to 6 h post-IVI.

PMID- 28508562
TI  - Can serological methods help distinguish between prophylactic and alloimmune anti
      D?
AB  - OBJECTIVES: Enzyme indirect antiglobulin test (EIAT) and polyethylene glycol IAT
      (PIAT) were evaluated for their potential use as tests to distinguish between
      prophylactic and alloimmune anti-D in plasma by comparing with a tube variation
      of the standard low ionic strength solution-IAT (LISS-IAT). BACKGROUND:
      Laboratories performing the screening of RhD-negative pregnant women are required
      to provide clinicians with guidance as to the source of detected RhD antibodies.
      Currently, this is derived from RhIg immunoprophylaxis history, agglutination
      scores and titration results, where performed. A serological test that can
      differentiate between prophylactic and alloimmune anti-D would be useful in the
      diagnosis of RhD alloimmunisation in pregnant women. MATERIALS AND METHODS:
      Plasma samples (n = 273) [fresh (collected from April 2014 to February 2015) and
      frozen (up to 2 years)] from antenatal females, preoperative males and females
      over child-bearing age were used in this study. Samples were identified as
      containing anti-D by routine column agglutination (CAT) and were tested by tube
      LISS-IAT, EIAT and PIAT, and a score difference was calculated. RESULTS: A total
      of 32% of alloimmune anti-D samples demonstrated an increase in agglutination
      score (+2 or +3) when tested by EIAT. A significant increase in agglutination
      score for alloimmune samples using EIAT compared with LISS-IAT was observed. EIAT
      had a sensitivity (Sn) of 59%, positive predictive value (PPV) of 100% and
      specificity (Sp) of 100% for alloimmune anti-D. CONCLUSION: EIAT is capable of
      confirming but not excluding the presence of alloimmune anti-D in samples where
      anti-D is detected in routine antibody screening.

PMID- 28508563
TI  - Safety Aspects of Immunoadsorption in IgG Removal Using a Single-Use, Multiple
      pass Protein A Immunoadsorber (LIGASORB): Clinical Investigation in Healthy
      Volunteers.
AB  - Therapeutic apheresis and immunoadsorption are used to deplete efficiently
      pathogenic autoantibodies in crises in several acute autoimmune driven diseases.
      This prospective, non-comparative cohort study was conducted at a single study
      center under standardized conditions in 10 healthy volunteers. Efficient
      immunoglobulin G (IgG) removal (-86% versus baseline) was achieved after 3
      apheresis treatments on 3 consecutive days. The treatments were well tolerated.
      Safety laboratory parameters did not show unexpected or pathological changes. The
      effects were transient, with most parameters exhibiting complete recovery between
      treatments. Minimal complement activation and moderate transient fibrinogen
      depletion were observed. Immunoadsorption with LIGASORB(r) provides a safe and
      effective treatment alternative to TPE in acute episodes of peripheral
      neurological diseases mediated by pathogenic IgG autoantibodies.

PMID- 28508564
TI  - Enantioselective Borylation of Aromatic C-H Bonds with Chiral Dinitrogen Ligands.
AB  - The borylation of C-H bonds catalyzed by transition metals has been investigated
      extensively in the past two decades, but no iridium-catalyzed enantioselective
      borylation of C-H bonds has been reported. We report a set of iridium-catalyzed
      enantioselective borylations of aromatic C-H bonds. This reaction relies on a set
      of newly developed chiral quinolyl oxazoline ligands. This process proceeds under
      mild conditions with good to excellent enantioselectivity, and the borylated
      products can be converted to enantioenriched derivatives containing new C-O, C-C,
      C-Cl, or C-Br bonds.

PMID- 28508565
TI  - Menaquinone-4 enhances osteogenic potential of human amniotic fluid mesenchymal
      stem cells cultured in 2D and 3D dynamic culture systems.
AB  - Menaquinones, also known as Vitamin K2 family, regulate calcium homeostasis in a
      'bone-vascular cross-talk' and recently received particular attention for their
      positive effect on bone formation. Given that the correlation between
      menaquinones and bone metabolism to date is still unclear, the objective of our
      study was to investigate the possible role of menaquinone-4 (MK-4), an isoform of
      the menaquinones family, in the modulation of osteogenesis. For this reason, we
      used a model of human amniotic fluid mesenchymal stem cells (hAFMSCs) cultured
      both in two-dimensional (2D) and three-dimensional (3D; RCCSTMbioreactor) in
      vitro culture systems. Furthermore, to mimic the 'bone remodelling unit' in
      vitro, hAFMSCs were co-cultured in the 3D system with human monocyte cells (hMCs)
      as osteoclast precursors. The results showed that in a conventional 2D culture
      system, hAFMSCs were responsive to the MK-4, which significantly improved the
      osteogenic process through gamma-glutamyl carboxylase-dependent pathway. The same
      results were obtained in the 3D dynamic system where MK-4 treatment supported the
      osteoblast-like formation promoting the extracellular bone matrix deposition and
      the expression of the osteogenic-related proteins (alkaline phosphatase,
      osteopontin, collagen type-1 and osteocalcin). Notably, when the hAFMSCs were co
      cultured in a 3D dynamic system with the hMCs, the presence of MK-4 supported the
      cellular aggregate formation as well as the osteogenic function of hAFMSCs, but
      negatively affected the osteoclastogenic process. Taken together, our results
      demonstrate that MK-4 supported the aggregate formation of hAFMSCs and increased
      the osteogenic functions. Specifically, our data could help to optimize bone
      regenerative medicine combining cell-based approaches with MK-4 treatment.

PMID- 28508566
TI  - Initial observation of CIN2 does not appear to reduce quality of life in women
      under 25 years of age.
AB  - BACKGROUND: Although the patient perspective is implicit in the practice of
      medicine, research evaluating this remains scarce. In a climate where clinicians
      and policy-makers constantly strive to achieve more patient-centred models of
      care, this omission warrants attention. AIM: To assess health-related quality of
      life (HrQoL) in women under 25 years of age with cervical intra-epithelial
      neoplasia grade 2 (CIN2) receiving conservative management (colposcopy follow-up,
      with treatment if necessary) compared with those receiving immediate excisional
      treatment with large loop excision of the transformation zone (LLETZ). METHODS:
      An observational study evaluating HrQoL was conducted at Christchurch Women's
      Hospital, New Zealand. Women undergoing conservative management for CIN2 were
      compared with those undergoing immediate excisional treatment in an age-matched
      sample. The Short Form Health Survey 12 version 2 (SF-12v2) was used to evaluate
      HrQoL. Secondary outcomes of anxiety and sexual function were also assessed.
      RESULTS: One hundred and four women with CIN2 participated in the study. Of
      these, 63 (60%) received conservative management and 41 (40%) received immediate
      excisional treatment with LLETZ. We found no significant difference in HrQoL
      between the groups in a multivariate regression analysis adjusted for parity,
      smoking and socioeconomic status. There were also no significant differences in
      sexual function or anxiety. CONCLUSION: We found no difference in HrQoL by
      management strategy. Conservative management of CIN2 in women under 25 is
      unlikely to have an adverse impact on self-reported HrQoL, anxiety or sexual
      functioning compared with conventional management.

PMID- 28508567
TI  - P Doped MoO3-x Nanosheets as Efficient and Stable Electrocatalysts for Hydrogen
      Evolution.
AB  - A P doped MoO3-x nanocomposite material with rich oxygen vacancies is
      successfully fabricated by a two-step intercalation method, which presents
      superior activity for the hydrogen evolution reaction with low overpotential and
      fast electron transfer. In 0.5 m H2 SO4 , it displays an overpotential of 166 mV
      for driving the current density of 10 mA cm-2 . Moreover, it also shows a good
      catalytic stability in the electrolytes with different pH, 0.5 m H2 SO4 (strong
      acid), 0.5 m Na2 SO4 (neutral solution), and 0.1 m NaOH (strong base). The
      superior catalytic activity and stability are due to to the synergistic effect
      between the P element doping and the oxygen vacancies.

PMID- 28508568
TI  - Randomized crossover trial of a pressure sensing visual feedback system to
      improve mask fitting in noninvasive ventilation.
AB  - BACKGROUND AND OBJECTIVE: A good mask fit, avoiding air leaks and pressure
      effects on the skin are key elements for a successful noninvasive ventilation
      (NIV). However, delivering practical training for NIV is challenging, and it
      takes time to build experience and competency. This study investigated whether a
      pressure sensing system with real-time visual feedback improved mask fitting.
      METHODS: During an NIV training session, 30 healthcare professionals (14 trained
      in mask fitting and 16 untrained) performed two mask fittings on the same healthy
      volunteer in a randomized order: one using standard mask-fitting procedures and
      one with additional visual feedback on mask pressure on the nasal bridge.
      Participants were required to achieve a mask fit with low mask pressure and
      minimal air leak (<10 L/min). Pressure exerted on the nasal bridge, perceived
      comfort of mask fit and staff- confidence were measured. RESULTS: Compared with
      standard mask fitting, a lower pressure was exerted on the nasal bridge using the
      feedback system (71.1 +/- 17.6 mm Hg vs 63.2 +/- 14.6 mm Hg, P < 0.001). Both
      untrained and trained healthcare professionals were able to reduce the pressure
      on the nasal bridge (74.5 +/- 21.2 mm Hg vs 66.1 +/- 17.4 mm Hg, P = 0.023 and 67
      +/- 12.1 mm Hg vs 60 +/- 10.6 mm Hg, P = 0.002, respectively) using the feedback
      system and self-rated confidence increased in the untrained group. CONCLUSION:
      Real-time visual feedback using pressure sensing technology supported healthcare
      professionals during mask-fitting training, resulted in a lower pressure on the
      skin and better mask fit for the volunteer, with increased staff confidence.

PMID- 28508569
TI  - Regulatory T cell signatures in liver transplant recipients successfully weaned
      from immunosuppression: Getting from here to there.

PMID- 28508571
TI  - Commentary on: Pratt SS, Losier BJ, Moulden HM, Chaimowitz GA. Incapacity of the
      mind secondary to medication misuse as a not criminally responsible defense. J
      Forensic Sci 2017;62(1):267-9.

PMID- 28508570
TI  - A new transcript in the TCRB locus unveils the human ortholog of the mouse pre
      Dbeta1 promoter.
AB  - INTRODUCTION: While most transcripts arising from the human T Cell Receptor locus
      reflect fully rearranged genes, several germline transcripts have been
      identified. We describe a new germline transcript arising from the human TCRB
      locus. METHODS: cDNA sequencing, promoter, and gene expression analyses were used
      to characterize the new transcript. RESULTS: The new germline transcript encoded
      by the human TCRB locus consists of a new exon of 103 bp, which we named TRBX1
      (X1), spliced with the first exon of gene segments Cbeta1 or Cbeta2. X1 is
      located upstream of gene segment Dbeta1 and is therefore deleted from a V-DJ
      rearranged TCRB locus. The X1-Cbeta transcripts do not appear to code for a
      protein. We define their transcription start and minimal promoter. These
      transcripts are found in populations of mature T lymphocytes from blood or
      tissues and in T cell clones with a monoallelic TCRB rearrangement. In immature
      thymocytes, they are already detectable in CD1a- CD34+ CD4- CD8- cells, therefore
      before completion of the TCRB rearrangements. CONCLUSIONS: The X1 promoter
      appears to be the ortholog of the mouse pre-Dbeta1 promoter (PDbeta1). Like
      PDbeta1, its activation is regulated by Ebeta in T cells and might facilitate the
      TCRB rearrangement process by contributing to the accessibility of the Dbeta1
      locus.

PMID- 28508572
TI  - Clinical characteristics and factors associated with mortality in idiopathic
      pulmonary fibrosis: An experience from a tertiary care center in Pakistan.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive
      interstitial lung disease (ILD) that predominantly affects older adults. IPF has
      the highest mortality burden of all ILDs. Data on mortality in patients with IPF
      is limited in developing countries. OBJECTIVES: To identify factors associated
      with mortality in patients with IPF at a tertiary care center in Pakistan.
      METHODS: A retrospective chart review was conducted at the Aga Khan University
      Hospital (AKUH) in Karachi, Pakistan from January 2005 to December 2015. Patients
      were assessed for smoking status, clinical onset of disease, pulmonary
      hypertension, disease severity based on spirometry and hypoxemia. RESULTS: A
      total of 239 cases were reviewed, of which 103 were non-survivors. A total of 45
      (18%) were current smokers and 71 (29.7%) were ex-smokers. Smoking was more
      common in non-survivors (56.3% P <= .01). Pulmonary hypertension was present in
      18.8% of patients. 95.4% of patients who had received pirfenidone treatment were
      alive at the time of study. On multivariate analysis, pirfenidone treatment (OR
      0.03; 95% CI 0.01-0.08), current smoking (OR 2.60; 95% CI 1.04-6.58), age older
      than 60 years (OR 2.63; 95% CI 1.04-6.58) and hypoxemia (OR 3.29; 95% CI 1.58
      6.84) were the factors associated with mortality. CONCLUSION: Smoking, age
      greater than 60 years and hypoxemia were identified as factors that increased the
      odds of mortality in IPF patients, whereas pirfenidone was found to lower the
      odds of mortality.

PMID- 28508574
TI  - Isomer-Selective Generation and Spectroscopic Characterization of Picolyl
      Radicals.
AB  - Nitrogen-containing resonance-stabilized radicals such as the picolyl radical are
      important in combustion chemistry and astrochemistry. They have only been
      scarcely studied because an isomer-selective generation is often difficult.
      Herein, we present threshold photoelectron spectra of the three picolyl radical
      isomers, C6 H6 N, that were obtained with synchrotron radiation. The radicals
      were selectively generated by flash pyrolysis from aminomethylpyridine precursors
      through deamination. Ionization energies of 7.70, 7.59, and 8.01 eV were
      determined for 2-, 3-, and 4-picolyl, respectively. The observed vibrational
      structure was assigned to an in-plane deformation mode of the aromatic ring. The
      spectroscopic insight gained in this study can be used to distinguish different
      picolyl isomers in on-line combustion analysis, for example.

PMID- 28508573
TI  - Regional differences in the management and outcome of kidney transplantation in
      patients with human immunodeficiency virus infection: A 3-year retrospective
      cohort study.
AB  - BACKGROUND: In the developed world, kidney transplantation (KT) in patients with
      human immunodeficiency virus (HIV) infection is well established. Developing
      countries concentrate 90% of the people living with HIV, but their experience is
      underreported. Regional differences may affect outcomes. OBJECTIVES: We compared
      the 3-year outcomes of patients with HIV infection receiving a KT in two
      different countries, in terms of incomes and development. METHODS: This was an
      observational, retrospective, double-center study, including all HIV-infected
      patients >18 years old undergoing KT. RESULTS: Between 2005 and 2015, 54 KTs were
      performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had
      less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia
      time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection
      (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes
      (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in
      Spain; P=.663. All three cases of death in Brazil were a result of bacterial
      infections within the first year post transplant. At 3 years, survival free from
      immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir
      based treatment to avoid interaction with calcineurin inhibitor was more
      prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in
      all patients, with undetectable viral load and no opportunistic infections.
      CONCLUSION: Important regional differences exist in the demographics and
      management of immunosuppression and antiretroviral therapy. These details may
      influence AR and infectious complications. Non-AIDS infections leading to early
      mortality in Brazil deserve special attention.

PMID- 28508575
TI  - Upregulation of inflammatory mediators in the ventricular zone after cortical
      stroke.
AB  - PURPOSE: After cortical stroke, neural precursor cells (NPCs) in the distal
      ventricular zone (VZ) proliferate more rapidly and migrate toward the injured
      cortex. While evidence suggests this can enhance stroke recovery, the underlying
      molecular mechanisms initiating the response are poorly understood. Here we
      identified changes in protein expression in the ipsilateral VZ early (4 h) after
      stroke to gain insight into the initial mechanisms involved in NPC activation
      post-stroke. EXPERIMENTAL DESIGN: Four hours after photothrombotic stroke (or
      sham surgery control) in the sensorimotor cortex, adult mice (10 stroke, 10 sham)
      were subjected to cardiac perfusion with PBS, and ipsilateral and contralateral
      VZ tissue was microdissected. Two separate sets of ipsilateral and contralateral
      VZ tissues (from 5 pooled surgery or 5 pooled sham mice) were analyzed
      simultaneously using 8-plex iTRAQ. We used Western blotting and confocal
      microscopy to confirm changes in protein expression in the VZ ipsilateral to
      stroke in a separate cohort of mice. RESULTS: We identified nine proteins which
      exhibited a significant mean increase (by >= 2-fold) in stroke ipsilateral
      compared to sham ipsilateral. Many of these proteins were antiproteases or
      cytokine/growth factor binding proteins that are known to act as inflammatory
      responders or effectors and play roles in modulating tissue growth and
      remodeling. CONCLUSION AND CLINICAL RELEVANCE: These novel findings support a
      growing body of literature that inflammatory signaling is involved in the NPC
      response to brain injury and identifies novel potential targets that could be
      exploited to better understand and to optimize this regenerative response.

PMID- 28508577
TI  - Intrinsic Notch Effect Leads to Breakdown of Griffith Criterion in Graphene.
AB  - Due to lack of the third dimension in 3D bulk materials, the crack tip in
      graphene locates on several atoms implying that its fracture behavior can be
      closely associated with its lattice structure, i.e., the bond length and angle.
      As the bond length reflects the discrete nature of the atomic structure,
      theoretical discussion is focused on the concomitant size effect at the nanoscale
      with few or no reports about the influence of the bond angle. Through the
      comparisons between theoretical calculations and experimental data, here it is
      first demonstrated that the bond angle is essential for understanding the
      fracture behavior in graphene, serving as an intrinsic notch reducing the stress
      singularity near the crack tip (the intrinsic notch effect), leading to the
      breakdown of the Griffith criterion in graphene. The work provides a framework
      for the studying of the brittle fracture in 2D materials, which gives rise to the
      more reliable device design based on 2D materials. More importantly, the
      significance of the intrinsic notch effect is profound and far-reaching, paving
      the way to a more comprehensive and deep understanding of the mechanical
      properties in nano as well as nanostructured materials.

PMID- 28508576
TI  - MHC I presentation of Toxoplasma gondii immunodominant antigen does not require
      Sec22b and is regulated by antigen orientation at the vacuole membrane.
AB  - The intracellular Toxoplasma gondii parasite replicates within a parasitophorous
      vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space,
      are inserted into PV membranes or are exported beyond the PV boundary. In
      addition to supporting T. gondii growth, these proteins can be processed and
      presented by MHC I for CD8+ T-cell recognition. Yet it is unclear whether
      membrane binding influences the processing pathways employed and if topology of
      membrane antigens impacts their MHC I presentation. Here we report that the MHC I
      pathways of soluble and membrane-bound antigens differ in their requirement for
      host ER recruitment. In contrast to the soluble SAG1-OVA model antigen, we find
      that presentation of the membrane-bound GRA6 is independent from the SNARE
      Sec22b, a key molecule for transfer of host endoplasmic reticulum components onto
      the PV. Using parasites modified to secrete a transmembrane antigen with opposite
      orientations, we further show that MHC I presentation is highly favored when the
      C-terminal epitope is exposed to the host cell cytosol, which corresponds to GRA6
      natural orientation. Our data suggest that the biochemical properties of antigens
      released by intracellular pathogens critically guide their processing pathway and
      are valuable parameters to consider for vaccination strategies.

PMID- 28508578
TI  - Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy
      treatment reveals potential roles for lysosomes and caspase-6 during tumor cell
      death in vivo.
AB  - The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an
      established in vivo apoptosis model for the investigation of novel cancer imaging
      agents and immunological treatments due to the rapid and significant response of
      the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy.
      Despite the utility of this model system in cancer research, little is known
      regarding the molecular details of in vivo tumor cell death. Here, we report the
      first in-depth quantitative proteomic analysis of the changes that occur in these
      tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free
      quantitative proteomic approach a total of 5838 proteins were identified in the
      treated and untreated tumors, of which 875 were determined to change in abundance
      with statistical significance. Initial analysis of the data reveals changes that
      may have been predicted, such as the downregulation of ribosomes, but
      demonstrates the robustness of the dataset. Analysis of the dataset also reveals
      the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in
      addition to a global upregulation of lysosomal proteins in the bulk of the tumor.

PMID- 28508579
TI  - Childhood obesity treatment: telephone coaching is as good as usual care in
      maintaining weight loss - a randomized controlled trial.
AB  - There is a need for more flexible treatment strategies to help patients reach
      relevant treatment outcomes and adhere better to treatment. The aim of this study
      was to evaluate the long-term efficacy, in terms of patients' weight status, of
      replacing usual care (UC) physical visits with more frequent but shorter
      telephone coaching (TC) sessions as part of a structured childhood obesity
      treatment. In this controlled study, patients aged 5-14 years from the Sodertalje
      outpatient clinic, Sweden were randomized to either UC or TC over an 18-month
      period after participating in an initial standard obesity treatment programme.
      The patients were followed for a mean of 3.7 years. In total, 37 children (UC, n
      = 18 and TC, n = 19) were included, with a mean (standard deviation, SD) age of
      9.5 (2.6) years and a body mass index standard deviation score (BMI SDS) of 2.9
      (0.7). The change in BMI SDS did not differ between the groups during the study
      (P = 0.8). Both groups had similar changes in BMI SDS 3.7 years after the first
      visit to the clinic, TC = - 0.42 and UC = 0.52 BMI SDS units (P = 0.6 between
      groups). There were no gender differences. Furthermore, the average time
      clinicians spent with each patient during the study did not differ between the
      groups (P = 0.5). No patients were lost to follow-up during the study. In
      conclusion, the use of TC may offer greater flexibility in the treatment of
      paediatric obesity as it was non-inferior for both treatment efficacy and the
      time spent on treatment by healthcare personnel.

PMID- 28508582
TI  - Conceptualizing behavioural addiction in children and adolescents.

PMID- 28508583
TI  - Substrate-Specific Amino Acid Sensing Using a Molecular d/ l-Cysteine Probe for
      Comprehensive Stereochemical Analysis in Aqueous Solution.
AB  - The appearance of d-amino acids in mammals and humans has important implications
      in the life sciences. d/l-Amino acid mixtures play a key role in human physiology
      and pathology; thus, the introduction of artificial receptors for the real-time
      quantification of both the concentration and d/l composition of amino acids is
      very promising for the study of biological processes and for the diagnosis and
      treatment of diseases. We now report a sensing assay that is compatible with
      aqueous solutions and allows fast determination of the absolute configuration,
      enantiomeric composition, and overall amount of cysteine at micromolar
      concentrations. The method relies on fast UV and CD measurements, which provide
      accurate stereochemical information on samples covering a wide concentration
      range and drastically different d/l-cysteine ratios in simulated body fluids.
      Competition experiments show that other amino acids and biothiols do not
      interfere with the cysteine-targeted sensing.

PMID- 28508581
TI  - Effect of under- and overfeeding on sheep and goat milk and plasma enzymes
      activities related to oxidation.
AB  - Twenty-four dairy sheep and goats, respectively, were assigned each to three
      homogenous subgroups per animal species and fed the same diet in quantities which
      met 70% (underfeeding), 100% (control) and 130% (overfeeding) of their energy and
      crude protein requirements. The results showed that the underfed sheep in
      comparison with the control had significantly lower glutathione reductase (GR),
      superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities
      and total antioxidant capacity (measured with Ferric Reducing Ability of Plasma
      [FRAP] assay) in their blood plasma. A significant increase in the glutathione
      transferase (GST) and GPX activities, malondialdehyde content and total
      antioxidant capacity (measured with 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulphonic acid) [ABTS] assay) in the blood plasma of underfed goats compared with
      controls was observed, while the opposite happened for the GR and SOD activities.
      The underfeeding in both animal species caused a significant increase in the
      protein carbonyls (PC) content of their blood plasma. The overfeeding, compared
      with the control, caused a significant decline in the GPX activity and total
      antioxidant capacity (measured with FRAP) in the blood plasma of sheep while the
      opposite happened for the GPX and GST activities in the case of goats. The
      overfed animals, of both species, compared with the respective controls, had
      higher PC content in their blood plasma. The feeding level had no noticeable
      impact on the antioxidants' enzymes activities of milk in both animal species.
      Moreover, the underfeeding in the blood plasma and the overfeeding in milk of
      both animal species resulted into a significant increase in the PC content.
      Finally, only in sheep milk, the underfeeding, compared with the respective
      control, and overfeeding reduced significantly the total antioxidant capacity
      (measured with ABTS). The feeding level caused oxidative stress in both organism
      and milk but the response was different in animal species and needs further
      investigation.

PMID- 28508580
TI  - 37 year snacking trends for US children 1977-2014.
AB  - BACKGROUND: Previous studies have indicated that snacking is contributing to
      increased calorie intake of American children and that the energy density of
      snacks in US diets has increased in recent decades. OBJECTIVE: Examine short-term
      and long-term trends in the energy density and food sources of snacks for US
      children from 1977 to 2014, and examine whether trends differ between socio
      demographic groups. METHODS: We used data collected from eight nationally
      representative surveys of food intake in 49,952 US children age 2-18 years,
      between 1977 and 2014. Overall patterns of snacking, trends in energy intake from
      snacking, trends in food and beverage sources and energy density of snacks across
      race-ethnic, age, gender, education and income groups were examined. RESULTS: In
      all socio-demographic groups, there was a significant increase in per capita
      energy intake deriving from snacks from 1977 to 2014 (P < 0.01). Salty snack
      intake doubled over the study period, and sugar-sweetened beverage intake
      decreased overall from 1977 to 2014 but increased in Non-Hispanic Blacks. Non
      Hispanic Blacks had the largest increase in per capita intake from foods as a
      snack from 1977 to 2014. Children in the lowest poverty level and household
      education groups had more than 100% increase in calorie intake from snacks from
      1977 to 2014. CONCLUSIONS: We found that snacking behaviour in the USA differs
      between race-ethnic, household education, gender and income groups, yet snacking
      remains a significant component of children's diets and the foods consumed at
      these snacks are not the types of foods recommended by the US dietary guidelines.

PMID- 28508584
TI  - Human intestinal spirochetosis in Japanese patients aged less than 20 years:
      Histological analysis of colorectal biopsy and surgical specimens obtained from
      479 patients.
AB  - Human intestinal spirochetosis (HIS) is a condition in which spirochetes attach
      to and colonize the colorectal epithelium. To our knowledge, no comprehensive
      studies of HIS in young patient have been published in a developed country. This
      study aimed to determine the incidence and clinicopathological manifestations of
      HIS in Japanese patients aged less than 20 years. We retrospectively reviewed
      3605 biopsy and 92 surgical specimens obtained from 479 patients admitted to
      Shinshu University Hospital between 1997 and 2014. All slides were reviewed
      independently by two pathologists to confirm the histological presence of
      spirochetes. Among 387 patients who underwent biopsy, the most common pathologic
      diagnosis was ulcerative colitis (12.6%, n = 49). Additionally, about half of the
      biopsy specimens showed non-specific, mildly inflamed mucosa (50.6%, n = 196);
      only one of these cases was HIS. On the other hand, among the surgical specimens,
      we found no cases of HIS. We concluded that the incidence of HIS in Japanese
      young patients was 0.2% (1/479 cases). The incidence of HIS in Japanese young
      patients was very low, and one HIS case was associated with colitis with
      abdominal pain.

PMID- 28508585
TI  - Exploring the Molecular Growth of Two Gigantic Half-Closed Polyoxometalate
      Clusters {Mo180 } and {Mo130 Ce6 }.
AB  - Understanding the process of the self-assembly of gigantic polyoxometalates and
      their subsequent molecular growth, by the addition of capping moieties onto the
      oxo-frameworks, is critical for the development of the designed assembly of
      complex high-nuclearity cluster species, yet such processes remain far from being
      understood. Herein we describe the molecular growth from {Mo150 } and {Mo120 Ce6
      } to afford two half-closed gigantic molybdenum blue clusters {Mo180 } (1) and
      {Mo130 Ce6 } (2), respectively. Compound 1 features a hat-shaped structure with
      the parent wheel-shaped {Mo150 } being capped by a {Mo30 } unit on one side.
      Similarly, 2 exhibits an elliptical lanthanide-doped wheel {Mo120 Ce6 } that is
      sealed by a {Mo10 } unit on one side. Moreover, the observation of the parent
      uncapped {Mo150 } and {Mo120 Ce6 } clusters as minor products during the
      synthesis of 1 and 2 strongly suggests that the molecular growth process can be
      initialized from {Mo150 } and {Mo120 Ce6 } in solution, respectively.

PMID- 28508587
TI  - Organic-Inorganic Hybrid Perovskite with Controlled Dopant Modification and
      Application in Photovoltaic Device.
AB  - Organic-inorganic hybrid perovskite as a kind of promising photovoltaic material
      is booming due to its low-cost, high defect tolerance, and easy fabrication,
      which result in the huge potential in industrial production. In the pursuit of
      high efficiency photovoltaic devices, high-quality absorbing layer is essential.
      Therefore, developing organic-inorganic hybrid perovskite thin films with good
      coverage, improved uniformity, and crystalline in a single pass deposition is of
      great concern in realizing good performance of perovskite thin-film solar cell.
      Here, it is found that the introduction of suitable amounts of LiI plays a
      dramatically positive role in enlarging the grain size and reducing the grain
      boundaries of absorbing layer. In addition, the carrier lifetime and built-in
      potential of the LiI doped perovskite device are observed to increase. Thus, it
      leads to about 15% gain in solar cell efficiency comparing to that without the
      LiI doping. Meanwhile, a hysteresis reduction is observed and 18.16% power
      conversion efficiency is achieved in LiI doped perovskite device, as well.

PMID- 28508586
TI  - Role and regulation of autophagy and apoptosis by nitric oxide in hepatic
      stellate cells during acute liver failure.
AB  - BACKGROUND & AIMS: We previously found that hepatic stellate cell activation
      induced by autophagy maintains the liver architecture to prevent collapse during
      acute liver failure. Nitric oxide has shown to induce hepatic stellate cell
      apoptosis. Whether and how nitric oxide is involved in acute liver failure and
      autophagy remains unclear. METHODS: Acute liver failure patients were recruited
      to investigate the correlation between plasma nitric oxide levels and clinical
      features. Liver tissues were collected from chronic hepatitis patients by biopsy
      and from acute liver failure patients who had undergone liver transplantation.
      The expression of nitric oxide synthases and hepatic stellate cell activation
      (alpha-SMA), and autophagic activity (LC3) were investigated by
      immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot
      analysis, confocal microscopy, and flow cytometry in hepatic stellate cells
      treated with nitric oxide donors. RESULTS: Plasma nitric oxide level was
      significantly increased in patients with acute liver failure compared to those
      with cirrhosis (53.60+/-19.74 MUM vs 19.40+/-9.03 MUM, Z=-7.384, P<.001) and
      positively correlated with MELD-Na score (r=.539, P<.001), implicating nitric
      oxide in acute liver failure. At least some Nitric oxide was produced by
      overexpression of inducible nitric oxide synthases and endothelial nitric oxide
      synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo
      observation revealed that autophagy was inhibited in hepatic stellate cells based
      on decreased LC3 immunostaining, and in vitro experiments demonstrated that
      Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic
      stellate cell apoptosis, which was rescued by an autophagy inducer. CONCLUSIONS:
      Increased nitric oxide synthases/ nitric oxide promotes apoptosis through
      autophagy inhibition in hepatic stellate cells during acute liver failure,
      providing a novel strategy for the treatment of patients with acute liver
      failure.

PMID- 28508588
TI  - At the Cross Section of Thrombotic Microangiopathy and Atypical Hemolytic Uremic
      Syndrome: A Narrative Review of Differential Diagnostics and a Problematization
      of Nomenclature.
AB  - Complement-mediated atypical hemolytic uremic syndrome (aHUS) is a rare disease
      associated with high mortality and morbidity. Renal biopsies often indicate
      thrombotic microangiopathy (TMA). The condition is caused by an excessive
      activation of the alternative pathway leading to depositions of membrane attack
      complexes (MAC) on host cells. It may depend on mutations in complement
      components and regulatory proteins, or the formation of complement-specific
      antibodies. Mainly, an environmental trigger (e.g. infection) is needed for the
      excessive response to develop. The clinical characteristics are more or less
      shared with a wide range of diseases manifesting with microangiopathic hemolytic
      anemia. Because of prior deficits in pathogenic understanding, associated
      nomenclature has been based on clinical symptoms. New knowledge challenges these
      symptomatic definitions; however, an outdated terminology is still being applied
      in clinical practice to various extents. With respect to gained insights, it is
      more advantageous to rebuild the concepts on etiological and pathogenic grounds.
      The need for more distinct definitions is even more urgent in the light of the
      effective treatment regimen with eculizumab for complement-mediated aHUS. This
      review presents an up-to-date summary of the field of investigation, addresses
      the need for faster differential diagnostics and proposes a revised nomenclature
      based on the current pathogenic understanding.

PMID- 28508590
TI  - Absenteeism in Head Start and Children's Academic Learning.
AB  - Using nationally representative data from the Family and Child Experiences Survey
      2009 cohort (n = 2,842), this study examined the implications of 3- and 4-year
      old's absences from Head Start for their early academic learning. The findings
      from this study revealed that children who missed more days of school, and
      especially those who were chronically absent, demonstrated fewer gains in areas
      of math and literacy during the preschool year. Moreover, excessive absenteeism
      was found to detract from the potential benefits of quality preschool education
      and was especially problematic for the early learning of children who entered the
      Head Start program with a less developed skill set. Implications for policy and
      practice are discussed.

PMID- 28508589
TI  - Identification of a novel HLA allele, HLA-B*41:50, in a French individual.
AB  - The novel HLA-B*41:50 allele differs from HLA-B*41:01:01 by a single nucleotide
      substitution at codon 116.

PMID- 28508591
TI  - Serious Offenders: Using Evidence to Predict and Manage the Risk.
AB  - In response to the risk of serious further offences, an evidence-based approach
      is needed in risk management. A recent joint prison-probation inspection of the
      management of life sentence prisoners in six U.K. prisons found that the quality
      of assessment and plans to manage risk of harm to others was insufficient, with
      too much focus on the offender's verbal account. The present paper discusses
      observations of regular prisoner behaviour as the basis for predictions, and
      summarizes results of an evaluation of this methodology based on a sample of high
      risk category prisoners released into the community. Prison behaviour has not
      traditionally been seen as a valid risk marker for violent recidivism, which may
      be because typically only conspicuous high-level behaviours are considered by
      risk management panels. Our research suggests that we are neglecting a valuable
      source of information on risk by failing to observe on-going and consistent pre
      release behaviour. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28508592
TI  - Confining Functional Nanoparticles into Colloidal Imine-Based COF Spheres by a
      Sequential Encapsulation-Crystallization Method.
AB  - Here, a two-step method is reported that enables imparting new functionalities to
      covalent organic frameworks (COFs) by nanoparticle confinement. The direct
      reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5
      benzenetricarbaldehyde in the presence of a variety of metallic/metal-oxide
      nanoparticles resulted in embedding of the nanoparticles in amorphous and non
      porous imine-linked polymer organic spheres (NP@a-1). Post-treatment reactions of
      NP@a-1 with acetic acid under reflux led to crystalline and porous imine-based
      COF-hybrid spheres (NP@c-1). Interestingly, Au@c-1 and Pd@c-1 were found to be
      catalytically active.

PMID- 28508594
TI  - meso-Cumulenic 2H-Corroles from meso-Ethynyl-3H-corroles.
AB  - Alkynyl-substituted 3H-corrole 9 a was converted to [3]cumulenic 2H-corrole 10 a
      by treatment with trimethylsilyl chloride (TMSCl), and 1,3-butadiyne-bridged 3H
      corrole dimer 11 b was transformed into [5]cumulene-bridged 2H-corrole dimer 12 b
      by oxidation with PbO2 . Both 10 a and 12 b were metalated to form ZnII complexes
      10 a-Zn and 12 b-Zn. The structures of 10 a-Zn and 12 b-Zn show planar
      conformations with bond-length alternations that are analogous to those of
      tetraaryl [n]cumulenes. The cumulenic corrole dimers 12 b and 12 b-Zn display
      large NIR absorption bands in the range of 700-1400 nm (maximum epsilon~1.0*105 
      m-1  cm-1 ) owing to the effective pi-conjugation between the two corrole units
      through the [5]cumulene bridge.

PMID- 28508593
TI  - Missense variant pathogenicity predictors generalize well across a range of
      function-specific prediction challenges.
AB  - The steady advances in machine learning and accumulation of biomedical data have
      contributed to the development of numerous computational models that assess the
      impact of missense variants. Different methods, however, operationalize impact
      differently. Two common tasks in this context are the prediction of the
      pathogenicity of variants and the prediction of their effects on a protein's
      function. These are related but distinct problems, and it is unclear whether
      methods developed for one are optimized for the other. The Critical Assessment of
      Genome Interpretation (CAGI) experiment provides a means to address this question
      empirically. To this end, we participated in various protein-specific challenges
      in CAGI with two objectives in mind. First, to compare the performance of methods
      in the MutPred family with the state-of-the-art. Second and more importantly, to
      investigate the applicability of general-purpose pathogenicity predictors to the
      classification of specific function-altering variants without additional training
      or calibration. We find that our pathogenicity predictors performed competitively
      with other methods, outputting score distributions in agreement with experimental
      outcomes. Overall, we conclude that binary classifiers learned from disease
      causing mutations are capable of modeling important aspects of the underlying
      biology and the alteration of protein function resulting from mutations.

PMID- 28508596
TI  - In Memoriam: Juan Jorge Heinrich, MD, PhD (1937-2016).

PMID- 28508595
TI  - Silver nanoparticle deposited implants to treat osteomyelitis.
AB  - In this study, electrolytically deposited strongly adherent silver nanoparticles
      on stainless-steel (SS) implants were used for in situ osteomyelitis treatment.
      Samples were heat treated to enhance adhesion of silver on 316 L SS. Ex vivo
      studies were performed to measure silver-release profiles from the 316 L SS
      screws inserted in equine cadaver bones. No change in the release profiles of
      silver ions were observed in vitro between the implanted screws and the control.
      In vivo studies were performed using osteomyelitic rabbit model with 3 mm
      diameter silver-deposited 316 L SS pins at two different doses of silver: high
      and low. Infection control ability of the pins for treating osteomyelitis in a
      rabbit model was measured using bacteriologic, radiographic, histological, and
      scanning electron microscopic studies. Silver-coated pins, especially high dose,
      offered a promising result to treat infection in animal osteomyelitis model
      without any toxicity to major organs. (c) 2017 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 106B: 1073-1083, 2018.

PMID- 28508597
TI  - In Memoriam: Melvin M. Grumbach, MD, (1925-2016) Pediatric Endocrinologist,
      Scientist, Educator, Leader.

PMID- 28508598
TI  - For Debate: Should We Worry about Hematospermia in Adolescents and Young Men? A
      Report of Six Cases and Review of the Literature.
AB  - Hematospermia or hemospermia is defined as the presence of blood in ejaculate.
      The true prevalence of the condition is unknown because many cases escape the
      patient's notice, and remain unrecognized and unreported. There are two main aims
      in the patient evaluation: first, to ensure that there is no specific condition
      that is treatable; second, to reassure the patient's parents that no causative
      factor is present. Many physicians are unfamiliar with this disorder and this
      forms the basis for our current review. We performed an essentially English
      language search (Medline since 1966 to present and reference list of articles)
      for "hematospermia", or "hemospermia" in combination with "adolescents", "young
      adults", "genital diseases", "management" and "review". The authors' personal
      experience with 6 adolescents and young men (up to the age of 20 years) is also
      reported. Several anatomical structures contributing to the ejaculate may be the
      source of the hematospermia: seminal vesicles, prostate, testis and epididymis.
      Hematospermia is a generally benign and self-limited condition that is
      infrequently associated with significant underlying pathology. Once the diagnosis
      is clear, it is important to reassure the adolescent about the benign nature and
      self-limiting course of the condition and to provide appropriate treatment to
      help ensure the adolescent's normal sexual development.

PMID- 28508599
TI  - IMAGe and Related Undergrowth Syndromes: The Complex Spectrum of Gain-of-Function
      CDKN1C Mutations.
AB  - CDKN1C is a cyclin-dependent kinase Inhibitor and negative regulator of cellular
      proliferation. Recently, gain-of-function mutations in the PCNA domain of CDKN1C
      have been reported as the genetic basis of various growth-retarded syndromes
      including IMAGe syndrome, Russell Silver syndrome as well as a novel undergrowth
      syndrome that additionally exhibited early adulthood onset diabetes. This review
      summarizes the key clinical features and the molecular advances that have
      contributed to our understanding of this complex phenotypic spectrum.

PMID- 28508600
TI  - Endocrine Disorders Developing after Surgical Intervention of Craniopharyngioma
      in Children.
AB  - Craniopharyngiomas, albeit their benign nature, can cause severe damage to
      visual, hypothalamic, endocrine and neurologic functions which make their total
      resection an inevitable approach to save the patient's life. However, significant
      therapy-related long term complications make those traditional treatment options
      debatable and hazardous. This review will focus on the various complications that
      affect the childrens' quality of life considerably such as, diabetes insipidus,
      precocious puberty and hypothalamic obesity.

PMID- 28508601
TI  - Effects of Anorexia Nervosa on the Endocrine System.
AB  - Anorexia nervosa (AN) is characterized by severe undernutrition associated with
      alterations in multiple endocrine axes, which are primarily adaptive to the state
      of caloric deprivation. Hormonal changes include growth hormone (GH) resistance
      with low insulin like growth factor-1 (IGF-1) levels, hypothalamic hypogonadism,
      relative hypercortisolemia and changes in appetite regulating hormones, including
      leptin, ghrelin, and peptide YY. These alterations contribute to abnormalities in
      bone metabolism leading to low bone mass, impaired bone microarchitecture, and
      increased risk for fracture, and may also negatively impact cognition, emotions
      and mood. The best strategy to improve all biologic outcomes is weight and
      menstrual recovery. Physiological estrogen replacement improves bone accrual
      rates and measures of trait anxiety in adolescents with AN. Other therapies
      including testosterone and IGF-1 replacement, and use of DHEA with oral estrogen
      progesterone combination pills, bisphosphonates and teriparatide have also been
      studied to improve bone outcomes.

PMID- 28508602
TI  - Succinate-Dehydrogenase Deficient Paragangliomas/Pheochromocytomas: Genetics,
      Clinical Aspects and Mini- Review.

PMID- 28508603
TI  - Meeting Reports: Adolescence - a Transition to Adulthood Proceedings of the 24th
      Aschauer Soiree, held at Jurata, Poland, November 5th 2016.

PMID- 28508604
TI  - For Debate: Growth Hormone Treatment of Infants Born Small for Gestational Age
      should be Started at or before the First Year of Age.
AB  - Children born small for gestational age without early catch-up of somatic growth
      and head circumference subsequently remain short and suffer from various degrees
      of neurocognitive and psychological impairment. Based upon the role of growth
      hormone (GH) and insulin-like growth factor-I on early brain growth and
      maturation, we propose that GH treatment of these infants be instituted prior to
      their 2nd birthday.

PMID- 28508605
TI  - Disorders of Adrenal Steroidogenesis: Impact on Gonadal Function and Sex
      Development.
AB  - A defect in adrenal steroidogenesis may cause a disorder of sex development
      (DSD). Importantly, DSD of adrenal origin is not restricted to a genital
      phenotype but is in most cases accompanied by mild to severe impairment in
      glucocorticoid and/or mineralocorticoid synthesis. If a patient is suspected of
      DSD of adrenal origin evaluation of glucocorticoid and mineralocorticoid
      metabolism is therefore essential to provide adequate medical care in the case of
      a severe and potentially life-threatening insufficiency. The adrenal
      steroidogenic defects causing DSD, their clinical features and diagnostic work-up
      are discussed. In this review we provide an overview of defects in the adrenal
      steroidogenesis and its impact on gonadal function and sex development.

PMID- 28508607
TI  - Sequelae of GH Treatment in Children with PWS.
AB  - More than 15 years after rGH was granted marketing authorization for children
      with PWS, a review of the sequelae, side effects and safety issues of rGH therapy
      is timely. The publications on issues concerning respiratory function, glucose
      metabolism, fat mass, and scoliosis at baseline and with rGH treatment are herein
      presented. We discuss the impact of rGH side effects, make proposals to prevent
      or treat them, and emphasise the remaining questions and perspectives. As a
      whole, the benefit /risk ratio is positive, although questions are raised about
      the role of GH in premature pubarche and its long-term effects, particularly the
      potential long-term oncogenic risk. The organisation of care in dedicated or
      reference centres at the national and European level will facilitate the
      collection and analysis of data and serve as a paradigm for long-term follow-up.

PMID- 28508606
TI  - Surgery in Focal Congenital Hyperinsulinism (CHI) - The "Hyperinsulinism Germany
      International" Experience in 30 Children.
AB  - OBJECTIVES: Results of surgery for focal CHI in 30 children PATIENTS AND METHODS:
      All showed an ABCC8 or KCNJ11 mutation. After PET/CT in 29 children and PET/MRT
      in 1 case, frozen-section guided resection was performed, in left-sided cases by
      laparoscopy. Mean age at surgery was 11.7 months (2-49). RESULTS: In 28/30
      children, the PET/CT or MRT correlated with histopathology. In two cases, a focal
      lesion was undectable; one of these was cured, one not. In total, 24 children
      showed lesions with sizes of 5-12 mm. All were cured instantly. In four children
      with huge lesions in the pancreatic head, pathological cells remained at the
      resection margins. One child was cured instantly, two children after a 2nd
      surgery, and one child was not cured, even after three surgeries. The overall
      cure rate was 93%. CONCLUSIONS: Imaging, surgical findings, histopathology and
      clinical outcome in surgery for focal CHI match in most, but not all cases.

PMID- 28508608
TI  - Myopathy in Pediatric Thyroid States: A Review of the Literature.
AB  - This review highlights the presentations of myopathy in children in both
      hypothyroid and hyperthyroid states with an emphasis on the pathophysiology,
      diagnosis and treatment. Based on our review of the literature data, myopathy
      should be considered in all children presenting with muscular weakness or altered
      muscle enzymes in the context of thyroid disease.

PMID- 28508609
TI  - Oral Health in Children with Obesity or Diabetes Mellitus.
AB  - Oral health status must be considered in the care of children with obesity (OB)
      and diabetes mellitus (DM). The health of these patients' mouths may have
      significant effects on their overall health and evolution of their disease. Here
      we address periodontal disease (PD) and dental caries (DC), since these are two
      of the most common chronic diseases affecting OB and DM patients. OB plays a
      plausible role in the development of PD. Both overall OB and central adiposity
      are associated with increased hazards of gingivitis and its progression to PD.
      The inflammatory changes of PD might not be limited to the oral cavity, these may
      also trigger systemic consequences. Patients with type 1 and type 2 diabetes
      mellitus (T1DM, T2DM) present an increased prevalence of gingivitis and PD. In
      diabetics PD develops at a younger age than in the healthy population, it also
      worsens with the prolongation of DM. The progression to PD has been correlated
      with the metabolic control of the disease as it is more prevalent and more severe
      in patients with elevated hemoglobin A1c (A1c) levels. PD negatively affects
      glycemic control and other diabetes related complications and there is a general
      consensus that treatment of PD can positively influence these negative effects.
      Additionally, DC is a multifactorial oral disease that is frequently detected in
      those with OB and DM, although its prevalence in systematic reviews is
      inconclusive. The associations between gingivitis, PD and DC share similar
      behaviors, i.e. inadequate oral hygiene habits and unhealthy dietary intake.
      Insufficient tooth brushing and intake of sugary foods may result in greater
      detrimental oral effects. Maintaining oral health will prevent oral chronic
      diseases and ameliorate the consequences of chronic inflammatory processes. Thus,
      the care of obese and diabetic patients requires a multidisciplinary team with
      medical and dental health professionals.

PMID- 28508610
TI  - Meeting Reports: 2016 Annual Meeting of the Pediatric Endocrine Society
      Baltimore, MD (April 29-May 2, 2016) Selected Highlights.

PMID- 28508611
TI  - Worth Remembering: Eugenio Muller, MD, 1933-2015.

PMID- 28508612
TI  - The Longevity Hormone Klotho is a New Player in the Interacion of the Growth
      Hormone/Insulin-Like Growth Factor 1 Axis.
AB  - Klotho was first discovered as an aging-suppressor gene. Mice that do not express
      klotho die prematurely with multiple symptoms of aging, several of which are also
      characteristic of decreased GH/IGF-1 axis activity. Klotho is highly expressed in
      the brain, the kidney, and parathyroid and pituitary glands, but can also serve
      as a circulating hormone by its shedding, forming soluble klotho (sKlotho) that
      can be detected in blood, cerebrospinal fluid and urine. Several lines of
      evidence suggest an association between klotho levels and activity of the GH/IHG
      1 axis: The GH-secreting cells in the anterior pituitary of klotho-deficient mice
      are hypotrophic; klotho levels are altered in subjects with pathologies of the
      GH/IGF-1 axis; and accumulating data indicate that klotho is a direct regulator
      of GH secretion. Thus, klotho seems to be a new player in the intricate
      regulation of the GH/IGF-1 axis.

PMID- 28508613
TI  - Genetic Mutations, Birth Lengths, Weights and Head Circumferences of Children
      with IGF-I Receptor Defects. Comparison with other Congenital Defects in the
      GH/IGF-I axis.
AB  - BACKGROUND: In recent years more and more genetic defects along the GHRH-GH-IGF-I
      axis have been reported. Mutations of the IGF-I receptor (R) are a rare
      abnormality of whom only the heterozygote progenies survive. OBJECTIVES: To
      summarize, from the literature, data on birth length, weight and head
      circumference of neonates with IGF-I-R mutations, and to correlate the data with
      that of other types of mutations in the GH/IGF-I axis. SUBJECTS: Sixty seven
      neonates from 24 published articles were included and forty seven different
      mutations of the IGF-I (R) located on chromosome 15 have been identified.
      RESULTS: Mean (+/-SD) birth length (BL), available for 26, (10 M, 16F) neonates
      with a gestational age of 34-41weeks, was 44.2+/-4cm; one was premature (30cm at
      31 weeks). There was a significant correlation between birth length and
      gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M,
      23F) was 2388+/-743gr. Two premature neonates weighed 650gr and 950gr
      respectively. The BW correlated significantly with gestational age, (males:
      r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6
      to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16
      mothers were short (133 -148cm), m+/-SD = 150.5+/-7.3cm.

PMID- 28508614
TI  - Methods for Rating Sexual Development in Girls.
AB  - Sexual maturity rating (SMR) is important in population studies and in clinical
      care. Pubertal staging allows doctors to assess the maturation of adolescents to
      correlate several pubertal phenomena such as age at menarche, growth spurt and
      final height, to advise and manage patients appropriately and to have sensitive
      "sensors" of the effects of environmental exposure on human populations. The
      commonly used markers of the timing of female puberty are thelarche and menarche.
      Appearance of the breast bud is the first indicator of puberty onset in 90% of
      girls. Assessment of thelarche may be performed by a physician with expertise in
      adolescents or by self-assessment, in which the adolescent identifies her stage
      of maturation based on Tanner's photographs/illustrations. The assessment of
      Tanner stages by professionals provides more reliable information than self
      assessment but may involve variations between observers. Tanner self-assessment
      has been proposed as an alternative in various studies. Some studies have found
      reasonable agreement between self-assessment and examination by a physician
      whereas others found discrepancies. Measuring nipple and areola diameters is
      feasible for sexual maturation staging. Both sizes show a significant increase
      during pubertal development and after menarche. However, the ratings using
      nipple/areola method need to be analyzed to establish their degree of concordance
      with standard techniques and other markers of development in girls.

PMID- 28508615
TI  - A Multidisciplinary Approach to Puberty and Fertility in Girls with Turner
      Syndrome.
AB  - Women with Turner Syndrome (TS) have a variety of medical needs throughout their
      lives; however, the peripubertal years are particularly challenging. From a
      medical perspective, the burden of care increases during this time due to growth
      optimization strategies, frequent health screenings, and puberty induction.
      Psychologically, girls begin to comprehend the long-term implications of the
      condition, including their diminished fertility potential. Unfortunately, clear
      guidelines for how to best approach this stage have not been established. It
      remains to be determined what is the best age to begin treatment; the best
      compound, dose, or protocol to induce puberty; how, when or what to discuss
      regarding fertility and potential fertility preservation options; and how to
      support them to accept their differences and empower them to take an active role
      in their care. Given the complexity of this life stage, a multidisciplinary
      treatment team that includes experts in endocrinology, gynecology, and psychology
      is optimal.

PMID- 28508617
TI  - Letters to the Editor: Response to "Thyroid Hemiagenesis from Childhood to
      Adulthood: Review of Literature and Personal Experience" by Vincenzo De Sanctis,
      MD, Ashraf T Soliman, MD, PhD, FRCP, Salvatore Di Maio, MD, Heba Elsedfy, MD,
      Nada A Soliman, MD, Rania Elalaily, MD.

PMID- 28508616
TI  - Ultrasound Elastography in Pediatric Congenital Hypothyroid Patients.
AB  - OBJECTIVES: Congenital hypothyroidism (CH) is most frequently encountered in
      newborns as an endocrine disorder characterized by thyroid hormone deficiency,
      and is one of the most common reasons for preventable mental retardation. This
      prospective study was designed to detect the pediatric occurrences of CH followed
      as euthyroid, with no anomalies detected via US on the gray scale, in comparison
      with a pediatric group with normal levels. METHODS: A total of 42 apparently
      healthy children with no thyroid disorder (Group 1) and 54 euthyroid CH (Group 2)
      using thyroid hormone were included in this study. Both B-mode gray scale
      ultrasound (US) and elastography examinations were made using Toshiba Aplio 400
      device (Toshiba Medical Systems Corporation, Otawara, Japan), with a 12 MHz
      linear probe. All the radiological examinations were made by a single radiologic
      physician with at least 5 years of experience in elastography. RESULTS: In total,
      96 occurrences in the right and left lobes of 192 thyroid gland measurements were
      included in the research. There were 20 males and 22 females in the healthy group
      (n=42), and 28 males and 26 females in the CH group (n=54). Although, there were
      no significant differences in the average age or gender (p=0.563), there were
      significant differences in the strain index (SI) values in the CH group.The
      receiver operating characteristics (ROC) curve was done to calculate the cut-off
      value for diagnosing CH with strain index ratio (SIR); the value of the cut-off
      was 0.695, with 63.1% sensitivity and 50.9% specificity. CONCLUSIONS: This was
      the first study about CH in children. Our study found the SIR of CH to be higher
      than the normal thyroid parenchyma. It showed that in parenchymal related CH, SE
      should be used. This study should be a guide for new studies that should be done
      about the different etiological factors of CH.

PMID- 28508618
TI  - Meeting Report: Festive Symposium Honoring Lynne L. Levitsky, MD, Boston April
      4th, 2016.

PMID- 28508619
TI  - Meeting Report: 2016 Annual Meeting of the Endocrine Society Boston, MA (April 1
      4, 2016) Selected Highlights.

PMID- 28508621
TI  - Extending the Use of Diffusive Gradients in Thin Films (DGT) to Solutions Where
      Competition, Saturation, and Kinetic Effects Are Not Negligible.
AB  - DGT (Diffusion Gradients in Thin films) was designed to sample trace metals in
      situ at their natural concentrations. The setup and the experimental deployment
      conditions were established to allow interpretation of a linear accumulation of
      metal with time, using a simple expression based on a steady-state flux under
      perfect sink conditions. However, the extension of DGT to a wide range of
      analytes and its use under varied conditions has shown that, in some situations,
      these conditions are not fulfilled, so that accumulations with time are
      nonlinear. Previously, when such curvature was observed, concentrations in
      solution could not be reliably calculated. Here, we present fundamentally derived
      equations that reproduce the time accumulation for three situations: (i) kinetic
      limitations in the binding to the resin, (ii) saturation or equilibrium effects,
      or (iii) non-negligible competitive effects. We show how the accumulations can be
      quantified, in terms of the required kinetic and thermodynamic constants, and
      provide practical guidance for their use to obtain reliable estimates of solution
      concentrations. Solutions containing Mg or Mn, where all three situations can
      prevail, are used as examples. Calculated concentrations show reasonable
      agreement with the experimentally known values and with the results of a
      numerical model of the system, significantly improving the estimations based on
      perfect sink conditions. Such an approach opens up the possibility of using DGT
      more widely in challenging systems and allows DGT data to be interpreted more
      fully.

PMID- 28508620
TI  - [Prevalence of human papillomavirus in Spanish women from a population screening
      program].
AB  - OBJECTIVE: The human papillomavirus (HPV), is necessary to cause a woman
      developing cervical cancer. The aim of the study was to estimate the prevalence
      of women with HPV infection, covered by the program of prevention and early
      detection of cervical cancer of Castile and Leon (Spain). METHODS: Samples of
      women included in the screening program were analyzed. Including a total of
      120,326 cervical swab samples, collected in the period from January 2012 to
      December 2014. RESULTS: 12,183 HPV positive samples were detected, representing a
      prevalence of 9.6 0/00, (IC 95% 9.5%-9.8%) in the female population. High-risk
      HPV were found in higher proportion that HPV low-risk genotypes. HPV prevalence
      correlates inversely with women age. Coinfections of multiple genotypes were
      found in one third of screened women population. CONCLUSIONS: Data showed in this
      study are the first and wider Spanish results from a cervical cancer screening
      program population non opportunistic based on HPV detection. These results would
      serve as a reference for future prevalence studies and to evaluate the future
      impact of HPV vaccination campaigns.

PMID- 28508622
TI  - Correlation of Interface Impurities and Chemical Gradients with High
      Magnetoelectric Coupling Strength in Multiferroic BiFeO3-BaTiO3 Superlattices.
AB  - The detailed understanding of magnetoelectric (ME) coupling in multiferroic oxide
      heterostructures is still a challenge. In particular, very little is known to
      date concerning the impact of the chemical interface structure and unwanted
      impurities that may be buried within short-period multiferroic BiFeO3-BaTiO3
      superlattices during growth. Here, we demonstrate how trace impurities and
      elemental concentration gradients contribute to high ME voltage coefficients in
      thin-film superlattices, which are built from 15 double layers of BiFeO3-BaTiO3.
      Surprisingly, the highest ME voltage coefficient of 55 V cm-1 Oe-1 at 300 K was
      measured for a superlattice with a few atomic percent of Ba and Ti that diffused
      into the nominally 5 nm thin BiFeO3 layers, according to analytical transmission
      electron microscopy. In addition, highly sensitive enhancements of the cation
      signals were observed in depth profiles by secondary ion mass spectrometry at the
      interfaces of BaTiO3 and BiFeO3. As these interface features correlate with the
      ME performance of the samples, they point to the importance of charge effects at
      the interfaces, that is, to a possible charge mediation of ME coupling in oxide
      superlattices. The challenge is to provide cleaner materials and processes, as
      well as a well-defined control of the chemical interface structure, to push
      forward the application of oxide superlattices in multiferroic ME devices.

PMID- 28508623
TI  - Integrating Nature, People, and Technology To Tackle the Global Agri-Food
      Challenge.

PMID- 28508624
TI  - Temperature Treatment of Highly Porous Zirconium-Containing Metal-Organic
      Frameworks Extends Drug Delivery Release.
AB  - Utilizing metal-organic frameworks (MOFs) as a biological carrier can lower the
      amount of the active pharmaceutical ingredient (API) required in cancer
      treatments to provide a more efficacious therapy. In this work, we have developed
      a temperature treatment process for delaying the release of a model drug compound
      from the pores of NU-1000 and NU-901, while taking care to utilize these MOFs'
      large pore volume and size to achieve exceptional model drug loading percentages
      over 35 wt %. Video-rate super-resolution microscopy reveals movement of MOF
      particles when located outside of the cell boundary, and their subsequent
      immobilization when taken up by the cell. Through the use of optical sectioning
      structured illumination microscopy (SIM), we have captured high-resolution 3D
      images showing MOF uptake by HeLa cells over a 24 h period. We found that
      addition of a model drug compound into the MOF and the subsequent temperature
      treatment process does not affect the rate of MOF uptake by the cell. Endocytosis
      analysis revealed that MOFs are internalized by active transport and that
      inhibiting the caveolae-mediated pathway significantly reduced cellular uptake of
      MOFs. Encapsulation of an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic
      acid (alpha-CHC), and subsequent temperature treatment produced loadings of up to
      81 wt % and demonstrated efficacy at killing cells beyond the burst release
      effect.

PMID- 28508625
TI  - High-Performance Red-Light Photodetector Based on Lead-Free Bismuth Halide
      Perovskite Film.
AB  - In this study, we developed a sensitive red-light photodetector (RLPD) based on
      CsBi3I10 perovskite thin film. This inorganic, lead-free perovskite was
      fabricated by a simple spin-coating method. Device analysis reveals that the as
      assembled RLPD was very sensitive to 650 nm light, with an on/off ratio as high
      as 105. The responsivity and specific detectivity of the device were estimated to
      be 21.8 A/W and 1.93 * 1013 Jones, respectively, which are much better than those
      of other lead halide perovskite devices. In addition, the device shows a fast
      response (rise time: 0.33 ms; fall time: 0.38 ms) and a high external quantum
      efficiency (4.13 * 103%). It is also revealed that the RLPD has a very good
      device stability even after storage for 3 months under ambient conditions. In
      summary, we suggest that the CsBi3I10 perovskite photodetector developed in this
      study may have potential applications in future optoelectronic systems.

PMID- 28508626
TI  - Red Emissive Sulfur, Nitrogen Codoped Carbon Dots and Their Application in Ion
      Detection and Theraonostics.
AB  - It is highly desirable and a great challenge for red light emission of carbon
      dots under long wavelength excitation. Here, we developed a facile route to
      synthesize carbon dots with red emission due to the doping effect of S and N
      elements, borrowing from the concept of the semiconductor. The maximum emission
      locates at 594 nm under 560 nm excitation. The absolute photoluminescence (PL)
      quantum yield (QY) is as high as 29% and 22% in ethanol and water, respectively.
      XPS and FTIR spectra illustrated that there exist -SCN and -COOH groups on the
      surface of the carbon dots. They endow the carbon dots with high sensitivity for
      ion detection of Fe3+. The quenched PL emission of Fe3+-S,N-CDs can be recovered
      by adding ascorbic acid to release the -COOH and -SCN group due to Fe2+ formation
      in the presence of ascorbic acid. High PL QY of red emission is beneficial to
      application in bioimaging. Doxorubicin was loaded onto carbon dots through pi-pi
      stacking to form a theranostic agent. When the CD-Dox was injected into the tumor
      site, a strong PL emission was observed. The PL intensity indicates the
      concentration of the theranostic agent. After 7 times injection, both the tumor
      size and weight clearly decrease. The results demonstrate that the S,N-CDs are a
      potentially excellent bioimaging component in the theranostic field.

PMID- 28508627
TI  - Fabrication of Ag-Cu2O/Reduced Graphene Oxide Nanocomposites as Surface-Enhanced
      Raman Scattering Substrates for in Situ Monitoring of Peroxidase-Like Catalytic
      Reaction and Biosensing.
AB  - Highly sensitive biosensors are essential in medical diagnostics, especially for
      monitoring the state of an individual's disease. An ideal way to achieve this
      objective is to analyze human sweat secretions by noninvasive monitoring. Due to
      low concentrations of target analytes in human secretions, fabrication of
      ultrasensitive detection devices is a great challenge. In this work, Ag
      Cu2O/reduced graphene oxide (rGO) nanocomposites were prepared by a facile two
      step in situ reduction procedure at room temperature. Ag-Cu2O/rGO nanocomposites
      possess intrinsic peroxidase-like activity and rapidly catalyze oxidation of the
      peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of
      H2O2. On the basis of the excellent SERS properties and high peroxidase-like
      activity of the Ag-Cu2O/rGO nanocomposites, the catalytic oxidation of TMB can be
      monitored by SERS. This approach can detect H2O2 and glucose with high
      sensitivity and distinguish between diabetic and normal individuals using glucose
      levels in fingerprints. Our work provides direction for designing other SERS
      substrates with high catalytic activity and the potential for application in
      biosensing, forensic investigation, and medical diagnostics.

PMID- 28508628
TI  - Defect Dominated Charge Transport and Fermi Level Pinning in MoS2/Metal Contacts.
AB  - Understanding the electronic contact between molybdenum disulfide (MoS2) and
      metal electrodes is vital for the realization of future MoS2-based electronic
      devices. Natural MoS2 has the drawback of a high density of both metal and sulfur
      defects and impurities. We present evidence that subsurface metal-like defects
      with a density of ~1011 cm-2 induce negative ionization of the outermost S atom
      complex. We investigate with high-spatial-resolution surface characterization
      techniques the effect of these defects on the local conductance of MoS2. Using
      metal nanocontacts (contact area < 6 nm2), we find that subsurface metal-like
      defects (and not S-vacancies) drastically decrease the metal/MoS2 Schottky
      barrier height as compared to that in the pristine regions. The magnitude of this
      decrease depends on the contact metal. The decrease of the Schottky barrier
      height is attributed to strong Fermi level pinning at the defects. Indeed, this
      is demonstrated in the measured pinning factor, which is equal to ~0.1 at defect
      locations and ~0.3 at pristine regions. Our findings are in good agreement with
      the theoretically predicted values. These defects provide low-resistance
      conduction paths in MoS2-based nanodevices and will play a prominent role as the
      device junction contact area decreases in size.

PMID- 28508630
TI  - On-Surface Heck Reaction of Aryl Bromides with Alkene on Au(111) with Palladium
      as Catalyst.
AB  - The on-surface Heck reaction of aryl bromides with terminal alkene has been
      achieved for the first time. With palladium as the catalyst, cross-coupling of
      porphyrin-derived aryl bromides with terminal alkene proceeds with high
      selectivity on an Au(111) surface, as determined by scanning tunneling microscopy
      at the single molecular level. Density functional theory calculations suggest
      that the on-surface Heck reaction proceeds via debromination of aryl bromide,
      addition to the C?C bond, and elimination of hydrogen, ultimately affording the
      cross-coupling product.

PMID- 28508629
TI  - Inorganic Ligand Thiosulfate-Capped Quantum Dots for Efficient Quantum Dot
      Sensitized Solar Cells.
AB  - The insulating nature of organic ligands containing long hydrocarbon tails brings
      forward serious limitations for presynthesized quantum dots (QDs) in photovoltaic
      applications. Replacing the initial organic hydrocarbon chain ligands with
      simple, cheap, and small inorganic ligands is regarded as an efficient strategy
      for improving the performance of the resulting photovoltaic devices. Herein,
      thiosulfate (S2O32-), and sulfide (S2-) were employed as ligand-exchange reagents
      to get access to the inorganic ligand S2O32-- and S2--capped CdSe QDs. The
      obtained inorganic ligand-capped QDs, together with the initial oleylamine-capped
      QDs, were used as light-absorbing materials in the construction of quantum dot
      sensitized solar cells (QDSCs). Photovoltaic results indicate that thiosulfate
      capped QDs give excellent power conversion efficiency (PCE) of 6.11% under the
      illumination of full one sun, which is remarkably higher than those of sulfide-
      (3.36%) and OAm-capped QDs (0.84%) and is comparable to the state-of-the-art
      value based on mercaptocarboxylic acid capped QDs. Photoluminescence (PL) decay
      characterization demonstrates that thiosulfate-based QDSCs have a much-faster
      electron injection rate from QD to TiO2 substrate in comparison with those of
      sulfide- and OAm-based QDSCs. Electrochemical impedance spectroscopy (EIS)
      results indicate that higher charge-recombination resistance between potoanode
      and eletrolyte interfaces were observed in the thiosulfate-based cells. To the
      best of our knowledge, this is the first application of thiosulfate-capped QDs in
      the fabrication of efficient QDSCs. This will lend a new perspective to boosting
      the performance of QDSCs furthermore.

PMID- 28508631
TI  - Reductive Bis-addition of Aromatic Aldehydes to alpha,beta-Unsaturated Esters via
      the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran Lignans.
AB  - The novel bis-addition of benzaldehydes to acrylates or maleates was achieved by
      the direct use of samarium metal with the assistance of CuI under mild conditions
      under dry air, and the useful 2-hydroxylalkyl-gamma-butyrolactons and lignan
      derivatives were thus constructed with high efficiency. The key factors that
      influence the reaction efficiency were investigated. The use of potassium iodide
      and molecular sieves as additives can improve the reaction efficiency remarkably.

PMID- 28508632
TI  - Colloidally Assembled Zinc Ferrite Magnetic Beads: Superparamagnetic Labels with
      High Magnetic Moments for MR Sensors.
AB  - Magnetic particles are widely used as labels in magnetoresistive sensors. To use
      magnetic particles as labels, several important characteristics should be
      considered, such as superparamagnetism, a high magnetic moment per particle (m),
      facile surface functionalization and biomolecule immobilization, colloidal
      stability, and analyte specificity. In this paper, we describe the preparation of
      magnetic labels with a high m, using colloidal assemblies of superparamagnetic
      zinc ferrite nanoparticles (ZFNPs, ~9 nm). Also, several properties of these
      particles are compared with those of commercially available magnetic beads,
      Dynabeads and TurboBeads. The colloidally assembled zinc ferrite magnetic beads
      (ZFMBs, ~160 nm) were synthesized by assembling ZFNPs via an emulsion-based
      assembly approach. While retaining superparamagnetism at room temperature, the m
      of ZFMBs is ~4000* higher than that of the constituent ZFNPs. Surface
      functionalization with a layer of polyacrylic acid stabilized the ZFMBs in
      aqueous solution and enabled conjugation with streptavidin via carbodiimide
      linking chemistry. The streptavidinated ZFMBs can be suspended in aqueous buffer
      for >=24 h, whereas 1.05 MUm Dynabeads and 30 nm TurboBeads undergo ballistic
      deposition and instantaneous aggregation in solution, respectively. Finally, the
      streptavidinated ZFMBs were employed as labels in an immunoassay for the
      detection of osteopontin, a potential pancreatic cancer marker, proving superior
      to the commercial particles in terms of limit of detection and dynamic range. We
      expect that the work presented in this article can be extended to other
      biological applications, especially where superparamagnetic particles with a high
      m and colloidal stability are needed.

PMID- 28508633
TI  - Ionic Complexes of Metal Oxide Clusters for Versatile Self-Assemblies.
AB  - The combination of rational design of building components and suitable
      utilization of driving force affords spontaneous molecular assemblies with well
      defined nanostructure and morphology over multiple length scales. The serious
      challenges in constructing assemblies with structural advantages for the
      realization of functions programmed into the building components usually lie
      ahead since the process that occurs does not always follow the expected roadmap
      in the absence of external intervention. Thus, prefabricated intermediates that
      help in governing the target self-assemblies are developed into a type of unique
      building blocks. Metal oxide cluster polyanions are considered as a type of
      molecular nanoclusters with size scale and structural morphology similar to those
      of many known inorganic particles and clusters but possess distinctive
      characteristics. Following the understanding of these clusters in self-assembly
      and the rationalization of their most efficient design strategy and approach, the
      obtained fundamental principles can also be applied in common nanoparticle- and
      cluster-based systems. On the other hand, the deliberate synergy offered by
      organic countercations that support the self-assembly of these clusters greatly
      expands the opportunity for the functionalization of complex building units via
      control of multiple interactions. The ionic combination of the inorganic clusters
      with hydrophilicity and the cationic organic component with hydrophobicity leads
      to discrete properties of the complexes. Significantly, the core-shell structure
      with rigid-flexible features and amphiphilicity will pave the way for
      hierarchical self-assemblies of the obtained complexes, while the intrinsic
      characteristics of the metal oxide clusters can be modulated through external
      physicochemical stimuli. Within this context, over the past decade we have
      extensively explored the ionic combination of inorganic polyanionic clusters with
      cationic organic amphiphiles and devoted our efforts to establishing the general
      rules and structure-property relationships of the formed complexes for
      constructing self-assemblies at the interface, in solution, and in solid
      matrixes. Specific interest has been focused on the functional synergy deriving
      from the incompatible components in highly organized self-assemblies. In this
      Account, we describe the recent progress on the ionic complexation of
      polyoxometalate clusters with cationic amphiphiles and the construction of
      diverse self-assembled nanostructures. First, the fundamental structural
      characteristics and molecular geometries of the prepared complexes are analyzed.
      The construction principle and diversity of the self-assembly based on the
      complexes and the smart stimuli response are then discussed, subject to the
      adjustment of various non-covalent interactions occurring in the assemblies.
      Subsequently, we enumerate the functional applications of the ionic complexes
      assembling into organic, inorganic, and even biological matrixes. The inspiration
      from the construction of ionic complexation and self-assembly in this Account
      provides vivid profiles for the design of hybrid materials involving nanoclusters
      and/or nanoparticles with rich potentials in addition to polyoxometalate
      chemistry.

PMID- 28508634
TI  - Interfacial Metal-Oxide Interactions in Resistive Switching Memories.
AB  - Metal oxides are commonly used as electrolytes for redox-based resistive
      switching memories. In most cases, non-noble metals are directly deposited as
      ohmic electrodes. We demonstrate that irrespective of bulk thermodynamics
      predictions an intermediate oxide film a few nanometers in thickness is always
      formed at the metal/insulator interface, and this layer significantly contributes
      to the development of reliable switching characteristics. We have tested metal
      electrodes and metal oxides mostly used for memristive devices, that is, Ta, Hf,
      and Ti and Ta2O5, HfO2, and SiO2. Intermediate oxide layers are always formed at
      the interfaces, whereas only the rate of the electrode oxidation depends on the
      oxygen affinity of the metal and the chemical stability of the oxide matrix.
      Device failure is associated with complete transition of short-range order to a
      more disordered main matrix structure.

PMID- 28508635
TI  - Polydopamine-Coated Manganese Carbonate Nanoparticles for Amplified Magnetic
      Resonance Imaging-Guided Photothermal Therapy.
AB  - This study reports a multifunctional nanoparticle (NP) that can be used for
      amplified magnetic resonance image (MRI)-guided photothermal therapy (PTT) due to
      its surface coating with a polydopamine (PDA) shell. Importantly, by means of
      introducing the surface coating of PDA, large quantities of water can be trapped
      around the NPs allowing more efficient water exchange, leading to greatly
      improved MR contrast signals compared with those from NPs without the PDA
      coating. Further, a distinct photothermal effect can be obtained arising from the
      strong absorption of PDA in the near-infrared (NIR) region. By synthesizing
      multifunctional MnCO3@PDA NPs, for example, we found that the longitudinal
      relaxivity (r1) of MnCO3 NPs can improve from 5.7 to 8.3 mM-1 s-1. Subsequently,
      in vitro MRI and PTT results verified that MnCO3@PDA could serve as an excellent
      MRI/PTT theranostic agent. Furthermore, the MnCO3@PDA NPs were applied as an
      MRI/PTT theranostic agent for in vivo MRI-guided photothermal ablation of tumors
      by intratumoral injection in 4T1 tumor-bearing mice. The MR imaging result shows
      a significantly bright MR image in the tumor site. The MnCO3@PDA-mediated PTT
      result shows high therapeutic efficiency as a result of high photothermal
      conversion efficiency. The present strategy of amplified MRI-guided PTT based on
      PDA coating of NPs will be widely applicable to other multifunctional NPs.

PMID- 28508637
TI  - Synthesis of Brominated Thiazoles via Sequential Bromination-Debromination
      Methods.
AB  - The synthesis of the full family of bromothiazoles has been revisited in order to
      update and optimize their production. The species reported include 2
      bromothiazole, 4-bromothiazole, 5-bromothiazole, 2,4-dibromothiazole, 2,5
      dibromothiazole, 4,5-dibromothiazole, and 2,4,5-tribromothiazole, the majority of
      which are produced via sequential bromination and debromination steps. This
      complete family can now be produced without the use of elemental bromine, and the
      presented methods have allowed the physical and NMR spectroscopic
      characterization of the full family to be reported for the first time.

PMID- 28508636
TI  - Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP
      Pyrophosphatase 1 Inhibitors.
AB  - The dCTP pyrophosphatase 1 (dCTPase) is a nucleotide pool "housekeeping" enzyme
      responsible for the catabolism of canonical and noncanonical nucleoside
      triphosphates (dNTPs) and has been associated with cancer progression and cancer
      cell stemness. We have identified a series of piperazin-1-ylpyridazines as a new
      class of potent dCTPase inhibitors. Lead compounds increase dCTPase thermal and
      protease stability, display outstanding selectivity over related enzymes and
      synergize with a cytidine analogue against leukemic cells. This new class of
      dCTPase inhibitors lays the first stone toward the development of drug-like
      probes for the dCTPase enzyme.

PMID- 28508638
TI  - Determination of the Absolute Configuration of beta-Chiral Primary Alcohols Using
      the Competing Enantioselective Conversion Method.
AB  - A method for determining the absolute configuration of beta-chiral primary
      alcohols has been developed. Enantioenriched alcohols were acylated in the
      presence of either enantiomer of the enantioselective acylation catalyst HBTM,
      and the faster reaction was determined by measuring product conversion using 1H
      NMR spectroscopic analysis. An empirical mnemonic was developed that correlates
      the absolute configuration of the alcohol to the faster reacting catalyst.
      Successful substrates for this method include primary alcohols that bear a
      "directing group" on the stereogenic center; directing groups include arenes,
      heteroarenes, enones, and halides.

PMID- 28508639
TI  - Polarizable and Non-Polarizable Force Field Representations of Ferric Cation and
      Validations.
AB  - The AMOEBA polarizable force field of ferric ion was optimized and applied to
      study the hydration of ferric ion and its complexation with porphine in the
      aqueous phase. The nonpolarizable force field was also optimized for comparison.
      The AMOEBA force field was found to give a more accurate hydration free energy
      than the nonpolarizable force field with respect to experimental data, and
      correctly predict the most stable electronic state of hydrated Fe3+, which is the
      sextet state, and of the Fe(III)-Por complex, which is the quartet state,
      consistent with the literature that was carried out using the DFT method. The
      explicit inclusion of charge transfer between Fe3+ and ligand was found to be
      important in order to obtain a precise picture of polarization energy and van der
      Waals energy, which otherwise deviate from the corresponding energy components
      derived from ab initio calculations. The successful application of the AMOEBA
      force field in the characterization of aquo Fe(III)-Por complexes suggests that
      its use may be extended to the study of the dynamics of metalloenzyme containing
      highly charged metal ions in the condensed phase with reliable treatment of the
      interactions between metal atom and protein.

PMID- 28508640
TI  - Construction of Polysubstituted 1,2-Dihydrocyclobuta[b]naphthalenes and 1,2
      Dihydrocyclobuta[b]anthracenes with Photoluminescence.
AB  - A facile protocol for the synthesis of polysubstituted 1,2
      dihydrocyclobuta[b]naphthalenes and 1,2-dihydrocyclobuta[b]anthracenes was
      developed via a sequence of base-promoted 1,5-H shift, intramolecular [2 + 2]
      cycloaddition, and aromatization. The synthesized 1,2
      dihydrocyclobuta[b]anthracenes exhibited bright blue emissions in solution and
      strong yellow emissions in solid, which made them possible candidates for
      optoelectronic conjugated materials.

PMID- 28508641
TI  - Intramolecular, Site-Selective, Iodine-Mediated, Amination of Unactivated (sp3)C
      H Bonds for the Synthesis of Indoline Derivatives.
AB  - The Iodine-mediated oxidative intramolecular amination of anilines via cleavage
      of unactivated (sp3)C-H and N-H bonds for the production of indolines is
      described. This transition-metal-free approach provides a straightforward
      strategy for producing (sp3)C-N bonds for use in the preferential
      functionalization of unactivated (sp3)C-H bonds over (sp2)C-H bonds. The reaction
      could be performed on a gram scale for the synthesis of functionalized indolines.

PMID- 28508642
TI  - Identification of Alternative Splice Variants Using Unique Tryptic Peptide
      Sequences for Database Searches.
AB  - Alternative splicing is a mechanism in eukaryotes by which different forms of
      mRNAs are generated from the same gene. Identification of alternative splice
      variants requires the identification of peptides specific for alternative splice
      forms. For this purpose, we generated a human database that contains only unique
      tryptic peptides specific for alternative splice forms from Swiss-Prot entries.
      Using this database allows an easy access to splice variant-specific peptide
      sequences that match to MS data. Furthermore, we combined this database without
      alternative splice variant-1-specific peptides with human Swiss-Prot. This
      combined database can be used as a general database for searching of LC-MS data.
      LC-MS data derived from in-solution digests of two different cell lines (LNCaP,
      HeLa) and phosphoproteomics studies were analyzed using these two databases.
      Several nonalternative splice variant-1-specific peptides were found in both cell
      lines, and some of them seemed to be cell-line-specific. Control and apoptotic
      phosphoproteomes from Jurkat T cells revealed several nonalternative splice
      variant-1-specific peptides, and some of them showed clear quantitative
      differences between the two states.

PMID- 28508644
TI  - Normal, Leveled, and Enhanced Steric Effects in Alkoxyamines Carrying a beta
      Phosphorylated Nitroxyl Fragment.
AB  - The design of new R1R2NOR3 alkoxyamines for various applications relies on the
      accurate prediction of two kinetic parameters, the C-ON bond homolysis rate
      constant (kd) and its re-formation rate constant (kc). Relationships to describe
      the steric and polar effects of the R1R2NO fragment ruling kd have been
      developed. For all cyclic nitroxyl fragments, the steric effect is described as
      the sum of the bulkiness of the R1 and R2 groups (i.e., normal steric effect),
      while for the noncyclic nitroxyl fragment (except for one case), a leveled steric
      effect is assumed. In this work, we show that the normal steric effect also
      applies to noncyclic nitroxyl fragments and that for one case an enhanced steric
      effect is also observed, i.e., experimental kd >5-fold larger than the predicted
      value.

PMID- 28508643
TI  - Correction to Enantio- and Diastereoselective Nitro-Mannich Reaction of alpha
      Aryl Nitromethanes with Amidosulfones Catalyzed by Phase-Transfer Catalysts.

PMID- 28508645
TI  - Pd(II)-Catalyzed Aerobic Intermolecular 1,2-Diamination of Conjugated Dienes: A
      Regio- and Chemoselective [4 + 2] Annulation for the Synthesis of
      Tetrahydroquinoxalines.
AB  - A Pd(II)-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes
      was developed for the regio- and chemoselective preparation of a variety of
      functionalized tetrahydroquinoxalines, using simple sulfonyl protected o
      phenylendiamines as a nitrogen source. This methodology provides a direct and
      efficient synthesis of tetrahydroquinoxalines. O2 was used as the stoichiometric
      oxidant, and reaction conditions were applied to a series of o-phenylendiamines
      and conjugated dienes. 35 examples are described, and good yields and
      selectivities are obtained for the majority of the products.

PMID- 28508646
TI  - Synthesis of Spiropentadiene Pyrazolones by Rh(III)-Catalyzed Formal sp3 C-H
      Activation/Annulation.
AB  - A Rh-catalyzed enol-directed formal sp3 C-H activation/annulation of alpha
      arylidene pyrazolones with alkynes has been developed. This reaction provides a
      convenient route to synthesize spiropentadiene pyrazolones in good to excellent
      yields at room temperature, exhibiting good functional group tolerance, gram
      scalability, and high regioselectivity. Of note, the alpha-arylidene pyrazolone
      was introduced as a novel C3 synthon in C-H activation/annulation.

PMID- 28508647
TI  - Copper-Promoted Desulfitative N-Arylation of Sulfonamides and Sulfoximines with
      Sodium Arylsulfinates.
AB  - A general and direct N-arylation of sulfonamides and NH-sulfoximines by sodium
      arylsulfinates through a desulfitative pathway was herein demonstrated. The
      reaction proceeded with catalytic loadings of Cu(II)-catalysts without any
      external ligands. And the novel arylation protocol featured for high efficiency
      (up to 93% yields) and good substituent tolerance (up to 53 examples). Moreover,
      a plausible reaction mechanism was also discussed.

PMID- 28508648
TI  - Photoredox-Catalyzed Diamidation and Oxidative Amidation of Alkenes: Solvent
      Enabled Synthesis of 1,2-Diamides and alpha-Amino Ketones.
AB  - Photoredox-catalyzed difunctionalizations of alkenes with O-acyl hydroxylamine
      derivatives are described. The solvent tunes the outcome of these reactions.
      Diamidation and oxidative amidation of alkenes can be achieved in CH3CN and DMSO,
      respectively. A variety of 1,2-diamidates and alpha-amino ketones bearing many
      functional groups are prepared using Ir(ppy)3 as the photocatalyst under visible
      light irradiation.

PMID- 28508650
TI  - Correction to "Pd-Catalyzed Conversion of Aryl Iodides to Sulfonyl Fluorides
      Using SO2 Surrogate DABSO and Selectfluor".

PMID- 28508649
TI  - Colloidal Synthesis of Te-Doped Bi Nanoparticles: Low-Temperature Charge
      Transport and Thermoelectric Properties.
AB  - Electronically doped nanoparticles formed by incorporation of impurities have
      been of great interest because of their controllable electrical properties.
      However, the development of a strategy for n-type or p-type doping on sub-10 nm
      sized nanoparticles under the quantum confinement regime is very challenging
      using conventional processes, owing to the difficulty in synthesis. Herein, we
      report the colloidal chemical synthesis of sub-10 nm-sized tellurium (Te)-doped
      Bismuth (Bi) nanoparticles with precisely controlled Te content from 0 to 5% and
      systematically investigate their low-temperature charge transport and
      thermoelectric properties. Microstructural characterization of nanoparticles
      demonstrates that Te ions are successfully incorporated into Bi nanoparticles
      rather than remaining on the nanoparticle surfaces. Low-temperature Hall
      measurement results of the hot-pressed Te-doped Bi-nanostructured materials, with
      grain sizes ranging from 30 to 60 nm, show that the charge transport properties
      are governed by the doping content and the related impurity and nanoscale grain
      boundary scatterings. Furthermore, the low-temperature thermoelectric properties
      reveal that the electrical conductivity and Seebeck coefficient expectedly change
      with the Te content, whereas the thermal conductivity is significantly reduced by
      Te doping because of phonon scattering at the sites arising from impurities and
      nanoscale grain boundaries. Accordingly, the 1% Te-doped Bi sample exhibits a
      higher figure-of-merit ZT by ~10% than that of the undoped sample. The synthetic
      strategy demonstrated in this study offers the possibility of electronic doping
      of various quantum-confined nanoparticles for diverse applications.

PMID- 28508651
TI  - Sugar-Breathing Glycopolymersomes for Regulating Glucose Level.
AB  - Diabetes mellitus is a chronic, life-threatening illness that affects people of
      every age and ethnicity. It is a long-term pain for those who are affected and
      must regulate their blood glucose level by frequent subcutaneous injection of
      insulin every day. Herein, we propose a noninsulin and antidiabetic drug-free
      strategy for regulating blood glucose level by a nanosized "sugar sponge" which
      is a lectin-bound glycopolymersome capable of regulating glucose due to the
      dynamic recognition between the lectin and different carbohydrates. The
      glycopolymersome is self-assembled from poly(ethylene oxide)-block-poly[(7-(2
      methacryloyloxyethoxy)-4-methylcoumarin)-stat-2-(diethylamino)ethyl methacrylate
      stat-(alpha-d-glucopyranosyl)ethyl methacrylate] [PEO-b-P(CMA-stat-DEA-stat
      GEMA)]. The lectin bound in the glycopolymersome has different affinity for the
      glucose in the blood and the glucosyl group in the glycopolymersome. Therefore,
      this sugar sponge functions as a glucose storage unit by dynamic sugar
      replacement: The lectin in the sugar sponge will bind and store the glucose from
      its surrounding solution when the glucose concentration is too high and will
      release the glucose when the glucose concentration is too low. In vitro, this
      sugar-breathing behavior is characterized by a remarkable size change of the
      sugar sponge due to the swelling/shrinkage at high/low glucose levels, which can
      be used for blood sugar monitoring. In vivo, this sugar sponge showed an
      excellent antidiabetic effect for type I diabetic mice within 2 days upon one
      dose, which is much longer than traditional long-acting insulin. Overall, this
      concept of "controlling sugar levels with sugar" opens new avenues for regulating
      the blood glucose level without the involvement of insulin or other antidiabetic
      drugs.

PMID- 28508652
TI  - New Infrared Bands of the C-Bonded Isomer of OC-N2O and Determination of Two
      Intermolecular Frequencies.
AB  - Three combination bands involving intermolecular modes of the most stable isomer
      of the OC-N2O van der Waals complex have been observed, two in the carbon
      monoxide CO stretch region (~2150 cm-1) and one in the nu3 asymmetric stretch
      region of N2O (~2223 cm-1). Vibrational assignment is achieved by comparison with
      data recently published ( Barclay , A. ; et al. Chem. Phys. Lett. 2016 , 62 , 651
      ), concerning OC-CO2. Two of these bands involve the same intermolecular mode,
      one with the CO stretch and the other with the nu3 asymmetric stretch of N2O. The
      values of intermolecular frequency deduced from these two bands agree very well,
      showing no significant dependence on intramolecular vibrational excitation.

PMID- 28508653
TI  - Synthesis and Reactivity of 5-Substituted Furfuryl Carbamates via
      Oxanorbornadienes.
AB  - Furfuryl carbamates are labile and require care to be accessed by activating
      furfuryl alcohols. An alternative oxanorbornadiene (OND)-based strategy is
      presented for the preparation of 5-R-substituted furfuryl carbamates via the
      reactions of amines with intermediate OND carbonates. The resulting OND
      carbamates, which are stable for several months, undergo thiol mediated retro
      Diels-Alder reaction to deliver the desired furfuryl carbamates in a single
      flask. Conditions for the selective hydrolysis of furfuryl carbamates in the
      presence of tert-butyloxycarbonyl (Boc) groups were identified, and it was shown
      that furfuryl carbamates can be used as a prodrug handle.

PMID- 28508654
TI  - Asymmetric Transfer Hydrogenation of 1,3-Alkoxy/Aryloxy Propanones Using Tethered
      Arene/Ru(II)/TsDPEN Complexes.
AB  - A series of propanones containing combinations of aryloxy and alkoxy substituents
      at the 1- and 3-positions were reduced to the alcohols via asymmetric transfer
      hydrogenation using a tethered Ru(II)/TsDPEN catalyst. The enantioselectivities
      of the reductions reveal a complex pattern of electronic and steric effects
      which, when used in a matched combination, can lead to the formation of products
      of up to 68% ee (84:16 er) from this highly challenging class of substrate.

PMID- 28508655
TI  - [Prevention of eating disorders].
AB  - The quality of the prevention of eating disorders represents in several last
      decades frequently discussed issue in the context of rapidly changing socio
      economic conditions, a significant increase of influence of the media, new
      technologies and knowledge of risk factors. Primary prevention aims to reduce the
      risk of developing eating disorders, but secondary and tertiary prevention play
      the important role as well. Effective and coordinated prevention is still
      missing. Our experience of international cooperation of the last 20 years led to
      the development and evaluation of prevention programs. We are describing their
      fast development and ongoing programs following the new trends recommended by
      WHO.

PMID- 28508656
TI  - [Prevention in psychiatry].
AB  - Mental disorders affect annually about one-fifth of the population and represent
      one of the biggest health burdens of the mankind in the 21st century. Despite
      great achievements of drug therapy, biological therapy and psychotherapeutic
      methods psychological problems in the present society are rather increasing.
      Therefore, attention also focuses on primary prevention of mental disorders,
      which is possible and effective.

PMID- 28508657
TI  - [Suicide a serious health and social problem with the possibility of prevention].
AB  - Suicide is a serious health and social problem whose incidence varies between
      genders, age groups, geographical distribution and with influence of socio
      political structure of society. It has been identified many risk factors and this
      behavior has etiological heterogeneity. There is no effective algorithm to
      predict suicidal activity in clinical practice, but increase the detection is
      associated with introducing the professional community and especially primary
      care physicians with clinical, psychological, sociological and biological factors
      whose can bring increasing of the recognition of vulnerable individuals and allow
      initiation of therapeutic interventions psychotherapy, psychopharmacology,
      neuromodulatory modalities or their combinations to achieve effective level of
      suicide prevention.

PMID- 28508658
TI  - [Life style and affective disorders].
AB  - Life style significantly affects the health status of each person. Life style
      medicine is an evidence based practice, which is trying to develop patterns of
      healthy behavior. Most evidence exists about the effect of suitable diet (eg.
      unsaturated fatty acids) and adequate aerobic exercise. Combination of lifestyle
      modification to standard psychopharmacologic and psychotherapeutic techniques can
      improve the results of preventive and therapeutic programs for people with
      depressive issues.

PMID- 28508659
TI  - [Work-related stress and mental health - can work lead to mental disorders?]
AB  - In the past two decades, special attention was paid to mental health issues. The
      available literature suggests, for example, the relationship between the workload
      and mental discomfort and the occurrence of myocardial infarction. This article
      focuses mainly on the issue of work-related stress and its impact on mental
      health. In this context, it must be acknowledged that possible psychological
      problems due to work are not only employees problem. These difficulties can
      significantly affect performance - and thus they should be the concern of the
      employer, but also of customers, clients and patients who come into contact with
      the worker who might develop some mental problems, due to the nature of his work
      and working conditions. This article provides an overview of the various factors
      affecting the mental health of employees. These are, for example, work demands,
      working hours and workplace relations. In conclusion, it brings results of Czech
      study examining job stress among working population.

PMID- 28508660
TI  - [A note on application of the WHOQOL-BREF questionnaire on quality of life in the
      Czech enviroment].
AB  - In the Czech environment, the WHOQOL-BREF (WHO Quality of Life-BREF)
      questionnaire has been rather frequently used for quality-of-life assessment in
      the case of different diseases or different health limitations. The questionnaire
      exists in two Czech translations with different wording. The differences are so
      considerable that they might cause interpretation shifts in research based on
      this instrument. Also the reverse scales in three questions may cause problems,
      because processing of these scores is not described correctly in some
      methodological materials. The authors recommend to strictly use the version
      published by Dragomirecka and Bartonova of the Prague Psychiatric Centre.

PMID- 28508662
TI  - Keeping Your Eyes Peeled for Corneal Ulcers.

PMID- 28508661
TI  - Post-transplant lymphoproliferative disease in liver transplant recipients.
AB  - INTRODUCTION: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and
      potentially life-threatening complication after liver transplantation. The aim of
      this study was to analyze the clinicopathologic features related to PTLD in a
      single institution after liver transplantation. METHODS: Observational study
      where we have retrospectively analyzed 851 cases who underwent liver
      transplantation. Ten cases have developed PTLD. Their clinical-pathological
      characteristics and the treatment received have been analyzed. RESULTS: PTLD
      incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD
      diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was
      extranodal in all cases, the most frequent location being intestinal. Seven cases
      showed a monomorphic lymphoma which in all cases was differentiated B cell
      lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus.
      Five patients were alive at the time of the review. Among these patients, we
      observed three cases of complete remission and two cases of disease
      stabilization. The death rate was higher in the first year after diagnosis of
      PTLD. CONCLUSION: PTLD is a rare complication after liver transplantation, but it
      may pose a threat to the life of a liver transplant recipient. It is essential to
      identify patients at risk, to establish an early diagnosis and treatment that can
      change the outcome of the disease.

PMID- 28508663
TI  - 18F-FDG PET/CT in polymyalgia rheumatica-a pictorial review.
AB  - Polymyalgia rheumatica (PMR) is one of the inflammatory rheumatic diseases that
      can potentially be detected by positron emission tomography/CT. High fluorine-18
      fludeoxyglucose (18F-FDG) accumulation around the shoulders, sternoclavicular and
      hip joints are the most common pre-treatment features of patients with PMR.
      Another common sign is increased 18F-FDG uptake in extra-articular regions
      between columnal spinous processes, near ischial tuberosities and in the
      praepubic area. Some patients also present with high 18F-FDG uptake in main
      arteries, corresponding to the characteristics of giant cell arteritis. It is
      possible to observe a decrease or even a disappearance of 18F-FDG uptake after
      effective therapy, an event which may be useful for the monitoring of treatment
      as well as for detection of PMR relapse.

PMID- 28508664
TI  - Aphrodisiac Activity of the Aqueous Crude Extract of Purple Corn ( Zea mays) in
      Male Rats.
AB  - In the present study, the aphrodisiac properties of the purple corn ( Zea mays)
      in male rats were analyzed. The aqueous crude extract of purple corn (at 25, 50,
      and 75 mg/kg) was administered to ( a) copulating male rats and ( b) anesthetized
      and spinal cord transected male rats. Behavioral parameters of copulatory
      behavior and parameters of the genital motor pattern of ejaculation previous to
      its inhibition, under the influence of the purple corn extract, are described.
      Administration of the aqueous crude extract of purple corn significantly
      facilitates the arousal and execution of male rat sexual behavior without
      significant influences on the ambulatory behavior. In addition, purple corn
      extract elicit a significant increase in the number of discharges of the
      ejaculatory motor patterns and in the total number of genital motor patterns
      evoked in spinal rats. The present findings show that the aqueous crude extract
      of purple corn possesses aphrodisiac activity.

PMID- 28508665
TI  - Prevalence of and risk factors for depressive symptoms among people living with
      HIV/AIDS receiving antiretroviral treatment in Wuhan, China: a short report.
AB  - We aimed to explore the prevalence of and risk factors for depressive symptoms
      (DS) among people living with HIV/AIDS (PLWHA) receiving antiretroviral treatment
      (ART) in Wuhan, Hubei, China. A cross-sectional study evaluating adult PLWHA
      receiving ART in nine designated clinical hospitals was conducted from October to
      December 2015. The validated Beck Depression Inventory (BDI) was used to assess
      DS in eligible participants. Socio-demographical, epidemiological and clinical
      data were directly extracted from the case reporting database of the China
      HIV/AIDS Information Network. Multinomial regression analysis was used to explore
      the risk factors for DS. 394 participants were finally included in all analyses.
      40.3% were found to have DS with 13.7% having mild DS and 26.6% having moderate
      to severe DS. The results of multinomial regression analysis suggested that being
      married or living with a partner, recent experience of ART-related side effects,
      and/or history of HCV infection were positively associated with mild DS, while
      increasing age was positively associated with moderate to severe DS.

PMID- 28508666
TI  - Biotransformation of total coumarins of Radix Glehniae by Lecanicillium
      attenuatum W-1-9.
AB  - The biotransformation of total coumarins of Radix Glehniae by Lecanicillium
      attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2),
      and lecaniside C (3). The chemical structures of these metabolites were
      elucidated based on extensive spectral data, including 2D NMR and HRMS. The
      hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these
      metabolites were observed in the present study. In the in vitro assays, compound
      1 displayed a little PTP1B inhibitory activity.

PMID- 28508667
TI  - Professionals' perspectives on a market-inspired policy reform: A guiding light
      to the blind spots of measurement.
AB  - Implementation of market-inspired competition and incentive models in health care
      is increasing worldwide, assumed to drive efficiency. However, the evidence for
      effects is mixed and unintended consequences have been reported. There is a need
      to better understand the practical consequences of such reforms. The aim of the
      present case study is to explore what consequences of a Swedish market-inspired
      patient choice reform professionals identify as relevant, and why. The study was
      designed as an explorative qualitative study in specialized orthopedics. Nineteen
      interviews were conducted with health care professionals at different providers.
      Data were analyzed using a hypo-deductive thematic approach. Consequences for the
      organization of care, patients, work environment, education and research were
      included in the professionals' analyses, covering both the perspective of their
      own organization and that of the health care system as a whole. In sum, the
      professionals provided multiple-level analyses that extended beyond the
      responsibilities of their own organization. Concluding, professionals are a
      valuable source of knowledge when evaluating policy reforms. Their analyses can
      contribute by covering a broad system perspective, serving as a guiding light to
      areas beyond the most obvious evaluation measures that should be included in more
      formal evaluations.

PMID- 28508668
TI  - Total synthesis and neuroprotective effect of O-methylmurrayamine A and 7
      methoxymurrayacine.
AB  - O-Methylmurrayamine A (7) and 7-methoxymurrayacine (8) are natural products
      isolated from Murraya koenigii and Murraya siamensis, respectively. In this
      paper, we report the synthesis of 7 and 8 which are featured in the key step of
      cyclization to form carbazole intermediate 5 with mild conditions. The structures
      were confirmed by 1H NMR, 13C NMR, and HR-ESI-MS. In addition, compounds 7 and 8
      were tested for their neuroprotective effects against H2O2-induced PC12 cell
      damage. The results showed that compounds 7 and 8 have neuroprotective effect.

PMID- 28508669
TI  - Efficient discrimination and removal of phospholipids during electromembrane
      extraction from human plasma samples.
AB  - AIM: For the first time, extracts obtained from human plasma samples by
      electromembrane extraction (EME) were investigated comprehensively with
      particular respect to phospholipids using ultra-high-performance liquid
      chromatography tandem mass spectrometry (UHPLC-MS/MS). Thhe purpose was to
      investigate the potential of EME for phospholipid cleanup in different EME
      systems. RESULTS & DISCUSSION: No traces of phospholipids were detected in any of
      the acceptor solutions, whereas the model analytes were extracted with recoveries
      up to 50%. Thus, the EME systems tested in this work were found to be highly
      efficient for providing phospholipid-free extracts. CONCLUSION: Ultra-HPLC-MS/MS
      analysis of the donor solutions revealed that the phospholipids principally
      remained in the plasma samples. This proved that the phospholipids did not
      migrate in the electrical field and they were prevented from penetrating the
      supported liquid membrane.

PMID- 28508670
TI  - Why did Sigmund Freud refuse to see Pierre Janet? Origins of psychoanalysis:
      Janet, Freud or both?
AB  - Pierre Janet and Joseph Breuer were the true originators of psychoanalysis. Freud
      greatly elaborated on their findings. Freud initially admitted these facts but
      denied them in later life. Janet discovered the concept transference before
      Freud.

PMID- 28508671
TI  - Chemometric profile, antioxidant and tyrosinase inhibitory activity of Camel's
      foot creeper leaves (Bauhinia vahlii).
AB  - The present study is the first effort to a comprehensive evaluation of
      antityrosinase activity and chemometric analysis of Bauhinia vahlii. The
      experimental results revealed that the methanol extract of Bauhinia vahlii (BVM)
      possesses higher polyphenolic compounds and total antioxidant activity than those
      reported elsewhere for other more conventionally and geographically different
      varieties. The BVM contain saturated fatty acids such as hexadecanoic acid
      (10.15%), octadecanoic acid (1.97%), oleic acid (0.61%) and cis-vaccenic acid
      (2.43%) along with vitamin E (12.71%), alpha-amyrin (9.84%), methyl salicylate
      (2.39%) and beta-sitosterol (17.35%), which were mainly responsible for
      antioxidant as well as tyrosinase inhibitory activity. Tyrosinase inhibitory
      activity of this extract was comparable to that of Kojic acid. These findings
      suggested that the B. vahlii leaves could be exploited as potential source of
      natural antioxidant and tyrosinase inhibitory agent, as well.

PMID- 28508672
TI  - Assessing infant-oriented care with developmental support approach in Iranian
      NICUs.
AB  - INTRODUCTION: Developmental care program is a comprehensive program to reduce
      secondary effects of NICU and special care on brain development in premature
      infants. This study aimed to assess neonatal care situation in Iranian NICUs
      based on developmental approach to design and provide clinical guidelines for
      daily care for the caregivers and the infant's family. METHODS: This was a cross
      sectional study conducted in NICUS in Iran. A total of 23 NICUs of 9 Universities
      of Medical Sciences were investigated. The checklist contains 30 items in 6
      domains. Data were analyzed using STATA software, version 13. RESULTS: The total
      mean score obtained from all six domains was 31.29 of 100, and in all domains,
      the mean scores calculated were not above 50. In "supporting infant,"
      "developmental caregiving activities," "supporting the infants' state
      organization," "providing neonatal pain management," "developmental care
      approaches in documentation," and "developmental care approaches in NICU
      staffing," the total mean scores were 34.76, 21.6, 20, 30.18, 31.30, and 50,
      respectively. CONCLUSION: The low mean score of infant-centered developmental
      care implies health staff's focus on neonatal care with at least the quality of
      care and its impact on development in preterm infants, and inadequate attention
      to the infant as an active member in care.

PMID- 28508673
TI  - Ayurvedic college education, reifying biomedicine and the need for reflexivity.
AB  - The paper analyses the experiences with government sanctioned Ayurvedic college
      education of 14 young Ayurvedic doctors working at the Integrative Health Centre
      in Bangalore, India. Unfamiliarity with Ayurvedic logic and Indian natural
      philosophies, lack of clinical training and the mixing-up of Ayurvedic and
      biomedical notions are their main complaints. The 14 young Ayurvedic doctors also
      missed a convincing perspective on how to integrate Ayurvedic logic, modern
      scientific knowledge and biomedical diagnostics. Ayurvedic state sanctioned
      education seems to be caught between Ayurveda's natural philosophy of health and
      the techno-science of biomedicine. The Ayurvedic doctors under scrutiny face the
      danger of becoming 'half-baked products' when they do not learn to reflect on the
      tension between Indian traditional knowledge and biomedical learning. The paper
      argues that the logic of modern science and biomedicine's claim to value-free
      knowledge captivates Ayurvedic education and research. This hinders Ayurveda's
      development as a vibrant alterity to biomedicine. What is needed is a critical
      social science perspective on the construction of medical knowledge and India's
      hierarchical medical landscape.

PMID- 28508674
TI  - Psychosocial screening and monitoring for children in foster care: Psychometric
      properties of the Brief Assessment Checklist in a Dutch population study.
AB  - Children in foster care experience higher levels and rates of psychosocial
      difficulties than children from the general population. Governments and child
      welfare services have a responsibility to identify those children in care who
      have need for therapeutic services. This can be achieved through systematic
      screening and monitoring of psychosocial difficulties among all children in
      foster care. However, general screening and assessment measures such as the
      Strengths and Difficulties Questionnaire (SDQ) and Child Behavior Checklist
      (CBCL) might not adequately screen for the range of difficulties experienced by
      foster children. The Brief Assessment Checklists for Children (BAC-C) and Brief
      Assessment Checklists for Adolescents (BAC-A) are measures designed to screen for
      and monitor attachment- and trauma-related difficulties among child welfare
      populations. This article reports psychometric properties of the BAC-C and BAC-A,
      estimated in a population study of 219 Dutch foster children. The results suggest
      the BAC-C and BAC-A perform both screening and monitoring functions well. Their
      screening accuracy, internal reliability and concurrent validity are comparable
      to those estimated for the SDQ within the same child and adolescent sample.
      Future research is needed to assess the value of the Brief Assessment Checklists
      (BAC) compared to other measures and to validate cut-points for the BAC. This
      study further establishes the BAC-A and BAC-C as valid and useful mental health
      screening and monitoring measures for use with children and adolescents in foster
      care.

PMID- 28508675
TI  - Serious mental illness among young adult women who use drugs in the club scene:
      co-occurring biopsychosocial factors.
AB  - Young women who regularly attend nightclubs are at risk for numerous health and
      social consequences, including mental distress, sexual and physical victimization
      and substance dependence. This paper uses a biopsychosocial framework to examine
      co-occurring mental health problems, victimization, substance dependence, sexual
      risk and physical pain among a sample of young women who use drugs (N = 222) in
      Miami's club scene. The majority of women were under 24 years old, Hispanic, and
      identified as heterosexual. Almost all the women reported past 90-day use of
      alcohol, ecstasy/MDMA, marijuana, cocaine and prescription opioids and
      benzodiazepines; 32% of women reported being in a monogamous relationship while
      41.9% reported having three or more sexual partners in the past 90 days; 65.3%
      met DSM-IV criteria for substance dependence; 60.4% met DSM-IV criteria for
      serious mental illness (SMI) and 59.9% were victimized as minors. Women who had
      SMI had higher odds of substance dependence, concurrent physical pain, three or
      more sexual partners in the past 90 days, childhood victimization and severe
      abuse-related trauma. The high levels of interconnected mental health,
      victimization, trauma, physical pain, substance dependence and sexual risk
      factors observed are underreported in the literature, as young women club scene
      participants appear to be more similar to other marginalized drug-involved
      populations than previously considered. While further research is needed, it
      appears these young women are in great need of outreach for primary health,
      mental health, HIV prevention, increased social support and substance abuse
      treatment services.

PMID- 28508676
TI  - Two new compounds from the fruiting bodies of Ganoderma philippii.
AB  - Two new compounds, philippin (1) and 3beta,9alpha,14alpha-trihydroxy-(22E,24R)
      ergost-22-en-7-one (2), were isolated from the fruiting bodies of Ganoderma
      philippii. Their structures were elucidated on the basis of the spectroscopic
      technologies, including 1D and 2D NMR as well as MS. The bioassay of inhibitory
      activity against acetylcholinesterase (AChE) showed compound 1 exhibited weak
      inhibitory activity against AChE.

PMID- 28508677
TI  - Ketonuria may be associated with low serum amylase independent of body weight and
      glucose metabolism.
AB  - CONTEXT: Ketonuria, which reflects a preferential combustion of lipids relative
      to carbohydrates, is often observed in lean rather than obese people. Clinical
      studies have shown that individuals with diabetes and/or obesity predispose to
      have low serum amylase (LSA). OBJECTIVE: To investigate the association between
      ketonuria and LSA. METHODS: We examined ketonuria assessed by dipstick urinalysis
      and clinical parameters including serum amylase in 3638 Japanese people aged 25
      79 years who underwent a health-screening checkup. RESULTS: There was an inverse
      relationship between body mass index (BMI) and serum amylase. The lowest serum
      amylase was observed in obese subjects (BMI >= 25.0 kg/m2) with positive
      ketonuria. Logistic regression analysis showed that ketonuria was significantly
      associated with LSA (<50 IU/L), which was not altered by the adjustments for
      relevant confounders including age, sex, BMI, and HbA1c. CONCLUSIONS: Current
      results suggest a relative unavailability of carbohydrates for energy production
      in individuals with LSA.

PMID- 28508678
TI  - Past is prologue: how to advance caregiver interventions.
AB  - OBJECTIVES: Research on caregiving interventions has increased substantially in
      recent years. Although many promising approaches have been tested, results are
      often modest. The goal of this paper is to identify conceptual and methodological
      issues that could lead to better treatment outcome. METHOD: A critical review of
      the literature on interventions for caregivers of persons with dementia. RESULTS:
      A fundamental issue in caregiver interventions is what are appropriate goals for
      treatment and what outcome measures should be used to address those goals. There
      also needs to be more testing of the mechanisms by which treatment leads to
      improvement. Intervention studies should also more regularly examine fidelity of
      treatment implementation. CONCLUSION: Recommendations are made for improving the
      design of future trials through better attention to the heterogeneity of the
      caregiving population, improved conceptualization of goals and the use of
      innovative designs that accommodate differences in caregivers' needs and
      resources.

PMID- 28508679
TI  - Comparison of FDG PET metabolic tumour volume versus ADC histogram: prognostic
      value of tumour treatment response and survival in patients with locally advanced
      uterine cervical cancer.
AB  - OBJECTIVE: To evaluate the prognostic utility of volume-based parameters of
      fluorine-18 fludeoxyglucose positron emission tomography (18F-FDG PET) and
      apparent diffusion coefficient (ADC) histogram analysis for tumour response to
      therapy and event-free survival (EFS) in patients with uterine cervical cancer
      receiving chemoradiotherapy. METHODS: The study included 21 patients diagnosed
      with locally advanced uterine cervical cancer who underwent pre-treatment MRI and
      18F-FDG PET and were treated with concurrent chemoradiotherapy. 18F-FDG
      parameters: maximum and mean standardized uptake value; metabolic tumour volume
      (MTV); total lesion glycolysis (TLG); ADC parameters: maximum, mean and minimum
      values; percentile ADC values (10-90%); skewness and kurtosis of ADC were
      measured and compared between the responder and non-responder groups using a
      Wilcoxon rank-sum test. The Cox regression analysis and Kaplan-Meier survival
      curves were performed for EFS analysis. RESULTS: MTV and TLG of the primary
      tumour were significantly higher in the non-responder group than in the responder
      group (p = 0.04 and p = 0.01). Applying Cox regression multivariate analysis, MTV
      [hazard ratio (HR), 4.725; p = 0.036], TLG (HR, 4.725; p = 0.036) and 10
      percentile ADC (HR, 5.207; p = 0.048) showed a statistically significant
      association with EFS. With the optimal cut-off value, the EFS rates above the cut
      off value for MTV and TLG were significantly lower than that below the cut-off
      value (p = 0.002 and p = 0.002). CONCLUSION: Pre-treatment volume-based
      quantitative parameters of 18F-FDG PET may have better potential than ADC
      histogram for predicting treatment response and EFS in patients with locally
      advanced cervical cancer. Advances in knowledge: In this study, pre-treatment
      volume-based quantitative parameters of 18F-FDG PET had better potential than ADC
      histogram for predicting treatment response and survival in patients with locally
      advanced cervical cancer.

PMID- 28508681
TI  - Correction to: Abhishek et al., Antioxidant and anti-inflammatory activities of
      Aerva pseudotomentosa leaves.

PMID- 28508680
TI  - Personality and destiny. Francesco Borromini: portrait of a tormented soul.
AB  - Francesco Borromini, one of the great geniuses of Baroque architecture, was
      tormented and solitary, and was increasingly frustrated by the fame and success
      of his rival, Gian Lorenzo Bernini. Borromini was an unhappy man, constantly
      dogged by disaster, quarrelling even with his best patrons and closest friends.
      In the culmination of one of the fits of depression that overcame the architect
      more and more frequently as his life progressed, Borromini literally fell on his
      own sword; he lingered in excruciating pain for 24 hours before dying. Largely
      forgotten, his architecture has again been recognized since the twentieth century
      as the creation of genius. We try to describe the personality and suicide of this
      pessimist giant of architecture.

PMID- 28508682
TI  - The risk of non-union per fracture: current myths and revised figures from a
      population of over 4 million adults.
AB  - Background and purpose - Fracture non-union remains a major clinical problem, yet
      there are no data available regarding the overall risk of fractures progressing
      to non-union in a large population. We investigated the rate of non-union per
      fracture in a large adult population. Methods - National data collected
      prospectively over a 5-year period and involving just under 5,000 non-unions were
      analyzed and compared to the incidence of fracture in the same period. Results
      and interpretation - The overall risk of non-union per fracture was 1.9%, which
      is considerably less than previously believed. However, for certain fractures in
      specific age groups the risk of non-union rose to 9%. As expected, these higher
      rates of non-union were observed with tibial and clavicular fractures, but-less
      expectedly-it was in the young and middle-aged adults rather than in the older
      and elderly population. This study is the first to examine fracture non-union
      rates in a large population according to age and site, and provides more robust
      (and lower) estimates of non-union risk than those that are frequently quoted.

PMID- 28508683
TI  - Effectiveness of mild ovarian stimulation versus GnRH agonist protocol in women
      undergoing assisted reproductive technology: a meta-analysis.
AB  - OBJECTIVE: our meta-analysis was conducted to evaluate the effectiveness of the
      mild ovulation induction protocol using CC/gonadotropin/GnRH antagonist compared
      to the conventional GnRH agonist protocol in women undergoing ART. METHOD: Six
      electronic databases were searched from their date of establishment until August
      2016. Outcomes in our analysis were calculated in terms of relative risk (RR) and
      weighted mean differences (WMD) and standard mean differences (SMD) with 95%
      confidence intervals (CI) using random effect models or fixed effect models.
      RESULTS: Six prospective controlled clinical trials with 1543 women comparing the
      clinical impacts of the two protocols were included. The synthesized results
      suggested a significant reduction in the quantity of gonadotropins (SMD: -1.96,
      95% CI: -2.28 to 1.64, I2 = 78.5%), the incidence of OHSS (RR: 0.16, 95% CI 0.03
      0.86, I2 = 0%) and an increase in the cycle cancelation rate (RR: 1.46, 95% CI
      1.05-2.03, I2 = 89.4%). While no evidence of statistically significant
      differences between the groups existed in the other clinical outcomes.
      CONCLUSION: This study suggested that the probable benefits of the mild protocol,
      including its less costs and safer process without reducing the overall IVF
      treatment success rates, seemed to make it a better treatment option. Larger
      sample prospective trials evaluating live birth, clinical pregnancy, OHSS,
      multiple pregnancy incidence and so on were desired to establish.

PMID- 28508684
TI  - Cutaneous Mixed Tumor and Recurrent Laryngeal Squamous Cell Carcinoma With
      Tyrosine-Rich Crystalloids: The Good, the Bad, and the Pretty.

PMID- 28508685
TI  - Primary Epidermoid Cyst of Biliary Duct Presenting as Choledochal Cyst.
AB  - Choledochal cyst is a cystic dilation of the biliary tree that can increase the
      risk of malignancy in bile ducts and the gallbladder. These are usually lined by
      bile duct epithelium, which may undergo intestinal and squamous metaplasia. This
      is the first report of clinically diagnosed type II choledochal cyst that is
      entirely lined by metaplastic stratified squamous epithelium, unlike most other
      cysts, which are histologically lined by bile duct epithelium. This observation
      can potentially explain the underlying pathogenic mechanism of rare reports of
      squamous cell carcinomas arising in bile duct systems.

PMID- 28508686
TI  - Malignant Peripheral Nerve Sheath Tumor of the Femur: A Rare Diagnosis Supported
      by Complete Immunohistochemical Loss of H3K27me3.
AB  - The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is
      challenging because of the wide morphological spectrum and suboptimal performance
      of conventional immunohistochemical markers. MPNST arising primarily in the bone
      is exceptional, and its definitive diagnosis, particularly out of the
      neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent
      inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss
      of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a
      highly specific biomarker of MPNSTs. In this article, we report a case of
      sporadic MPNST of the proximal femur that showed complete loss of H3K27me3. The
      patient was treated with limb-sparing surgery and postoperative radiotherapy. He
      developed multiple lung and bone metastases 4 months after surgery. Our case
      confirms the utility of H3K27me3 immunohistochemistry to yield a definitive
      diagnosis of sporadic MPNST in a rare primary site.

PMID- 28508687
TI  - Multilocular Thymic Cyst With Mucinous Differentiation: A Mimicker of Thymic
      Mucoepidermoid Carcinoma.

PMID- 28508688
TI  - Extrarenal Wilms Tumor With Skeletal and Glial Differentiation.

PMID- 28508689
TI  - Age, choline-to-N-acetyl aspartate, and lipids-lactate-to-creatine ratios
      assemble a significant Cox's proportional-hazards regression model for survival
      prediction in patients with high-grade gliomas.

PMID- 28508690
TI  - Gene polymorphisms associated with temperament.
AB  - When individuals are exposed to stressful environmental challenges, the response
      varies widely in one or more of three components: psychology, behavior and
      physiology. This variability among individuals can be defined as temperament. In
      recent years, an increasing large body of evidence suggests that the dimensions
      of temperament, as well as personality, psychological disorders and behavioral
      traits, are influenced by genetic factors, and much of the variation appears to
      involve variation in genes or gene polymorphisms in the hypothalamic-pituitary
      adrenocortical (HPA) axis and the behavior-controlling neurotransmitter networks.
      Here, we review our current understanding of the probabilistic impact of a number
      of candidate gene polymorphisms that control temperament, psychological disorders
      and behavioral traits in animals and human, including the gene polymorphisms
      related to corticotrophin-releasing hormone (CRH) production and adrenal cortisol
      production involved in the HPA axis, and a large number of gene polymorphisms in
      the dopaminergic and serotonergic neurotransmitter networks. It will very likely
      to assist in diagnosis and treatment of human relevant disorders, and provide
      useful contributions to our understanding of evolution, welfare and conservation,
      for animals in the wild and in production systems. Additionally, investigations
      of gene-gene and gene-environment complex interactions in humans and animals need
      further clear illustration.

PMID- 28508691
TI  - Corifollitropin alfa compared with follitropin beta in GnRH-antagonist ovarian
      stimulation protocols in an unselected population undergoing IVF/ICSI.
AB  - Recombinant DNA technologies have produced Corifollitropin alfa (CFa) used during
      IVF/ICSI in order to keep the circulating FSH levels above the threshold
      necessary to support multi-follicular growth for a week. In this prospective case
      control study, we compared 70 participants treated with 150 MUg CFa combined with
      150 IU of follitropin beta (study group) with 70 subfertile participants with
      matching baseline characteristics, conforming with the same inclusion criteria
      and treated with an antagonist protocol using follitropin beta (control group).
      Live birth was the primary outcome, while secondary outcome measures were
      IVF/ICSI cycles characteristics, including adverse events and complications. Live
      birth was determined in reduced rates in the study compared to the control group,
      reaching statistical significance [6/70 versus 20/70, p = 0.002], as also in the
      respective number of clinical pregnancies [9/70 versus 23/70, p = 0.005],
      although the incidence of miscarriage was similar for both groups [6/70 versus
      5/70, p > 0.99]. Most of the secondary parameters examined were similar between
      groups. Logistic regression revealed that protocol and AFC had a direct impact on
      live birth. Ovarian stimulation with CFa does not seem to constitute an equally
      effective method as compared with follitropin beta to be offered in a general
      subfertile population seeking IVF/ICSI treatments.

PMID- 28508693
TI  - A metabolite profiling method for diagnosis of precancerous cervical lesions and
      HPV persistence.
AB  - AIM: With the advent of rapid metabolic profiling techniques and of portable mass
      spectrometers we examined whether cells distinguished by their cytology and
      persistence of human papillomavirus infection, could be easily differentiated by
      their metabolite profile. MATERIALS & METHODS: Direct injection electrospray mass
      spectrometry was used in a nontargeted double-blind experiment. Samples were
      collected from women diagnosed with one of two grades of cervical cytology and
      exhibiting either human papilloma virus persistence or clearance. Cell extracts
      were prepared using a DNA extraction procedure and the resulting supernatant,
      normally discarded, was analyzed. Data were interpreted using principal component
      analysis. RESULTS: The results indicate strongly that a simple metabolite
      profiling method could be used to rapidly identify women at increased risk of
      cervical cancer.

PMID- 28508692
TI  - SEIFEM 2010-E: economic evaluation of posaconazole for antifungal prophylaxis in
      patients with acute myeloid leukemia receiving induction chemotherapy.
AB  - Posaconazole demonstrated clinical superiority over fluconazole and itraconazole
      for prophylaxis of mold infections, although concerns exist regarding the high
      acquisition cost for posaconazole. In this respect, we sought to analyze the
      costs of antifungal prophylaxis in patients with acute myeloid leukemia (AML) who
      received prophylactic posaconazole (n = 510, 58%), itraconazole (n = 120, 14%) or
      fluconazole (n = 175, 20%) during induction chemotherapy. The estimated cost of
      antifungal prophylaxis as well as the costs of subsequent systemic antifungal
      therapy for treatening an invasive fungal infections (IFI) was higher in the
      posaconazole group compared to itraconazole and fluconazole groups. Based on the
      Monte Carlo simulations, the itraconazole group had the highest cost, followed by
      the posaconazole and fluconazole group, although the overall survival was higher
      in the posaconazole group as compared to the other groups. In conclusion, the
      cost of prophylaxis with posaconazole in AML patients compares favorably with
      conventional antifungal agents.

PMID- 28508694
TI  - Online versus offline spatiotemporal image correlation (STIC) M-mode for the
      evaluation of cardiac longitudinal annular displacement in fetal growth
      restriction.
AB  - PURPOSE: Our first aim was to compare online M-mode with offline spatiotemporal
      image correlation (STIC) M-mode for assessing longitudinal annular displacement
      (LAD) in growth-restricted fetuses (FGR). Our second aim was to compare LAD
      measures of FGR cases with controls. MATERIALS AND METHODS: Prospective study
      including 40 FGR cases (defined estimated fetal weight and birth weight <10th
      centile) and 72 normally grown fetuses matched to cases by gestational age at
      scan. LAD was measured with online M-mode and offline STIC M-mode at the left and
      right ventricular free walls and septum in all fetuses. RESULTS: FGR cases had a
      significant decrease in LAD by STIC in all sites as compared to controls (e.g.
      right LAD in FGR mean 6.7 mm (SD 1.2) versus controls 7.2 mm (1.2), p = .033).
      There was a non-significant trend for lower values in FGR when using online M
      mode (e.g. right LAD in FGR 6.9 mm (1.5) versus controls 7.4 mm (1.5), p = .084).
      CONCLUSIONS: STIC M-mode seems a better method than online M-mode for detecting
      subtle changes in myocardial motion. STIC presents more precise results and
      allows an ideal placement of the M-mode arrow. These results confirm previous
      data suggesting decreased longitudinal motion in FGR.

PMID- 28508695
TI  - Ganglion Cells Are Frequently Present in Pediatric Mucosal Colorectal Biopsies:
      H&E Sections and Calretinin Immunohistochemistry in the Evaluation of Children
      With Chronic Constipation.
AB  - Hirschsprung disease (HD) rarely presents as chronic constipation after the
      newborn period. At our institution, calretinin immunohistochemistry (CAL) is
      frequently requested by clinicians on rectal mucosal biopsies (RMBs) taken during
      colonoscopy in older children in whom suspicion for HD is low. We hypothesized
      that review of these biopsies would frequently reveal ganglion cells (GCs). We
      reviewed features of mucosal biopsies (November 2013 to September 2015) from
      children >=1 year of age on which clinicians had requested CAL on at least one
      specimen. A total of 93 biopsies with paired CAL from 83 patients were suitable
      for study (ages 1-18 years, M:F 1.2). Submitted clinical indication was
      constipation in 62 patients (75%). GCs were found within or subjacent to
      muscularis mucosa in 63 biopsies (68%), 12 (19%) of which were designated from a
      specific anatomic site, eg, 2 or 3 cm. In 25 of 63 (40%) cases, GCs were
      identified on one of the first 3 sections (median 5th, range 1st-54th). Forty-six
      cases (73%) contained no or <0.5 mm of submucosa (SM, range 0-2 mm). All but one
      case (62/63, 98%) with identified GCs showed positive CAL staining; a single case
      showed equivocal staining. Among the 30 biopsies with no observed GCs, none (0%)
      had >1 mm of SM, and 21 (70%) had no SM. CAL was positive in 28 (93%) and
      equivocal/weak in 2 (7%); no additional work-up for HD was pursued. The data
      suggest that H&E sections of RMBs can exclude HD at a specified site in many
      cases and provide the basis for a future study examining the utility of CAL in
      RMBs without SM as a means for excluding HD.

PMID- 28508696
TI  - A bibliometric analysis of occupational therapy publications.
AB  - BACKGROUND: Bibliometrics involves the statistical analysis of the publications
      in a specific discipline or subject area. A bibliometric analysis of the
      occupational therapy refereed literature is needed. AIM: A bibliometric analysis
      was completed of the occupational therapy literature from 1991-2014, indexed in
      the Science Citation Index-Expanded or the Social Sciences Citation Index.
      METHOD: Publications were searched by title, abstract, keywords, and KeyWords
      Plus. Total number of article citations, citations per journal, and contributions
      per country, individual authors, and institution were calculated. RESULTS: 5,315
      occupational therapy articles were published in 821 journals. It appears that
      there is a citation window of an approximate 10-year period between the time of
      publication and the peak number of citations an article receives. The top three
      most highly cited articles were published in Developmental Medicine and Child
      Neurology, JAMA, and Lancet. AJOT, BJOT and AOTJ published the largest number of
      occupational therapy articles with the United States, Australia, and Canada
      producing the highest number of publications. McMaster University, the University
      of Queensland, and the University of Toronto were the institutions that published
      the largest number of occupational therapy journal articles. CONCLUSION: The
      occupational therapy literature is growing and the frequency of article citation
      is increasing.

PMID- 28508697
TI  - Collagen concentration on the facial skin of postmenopausal women after topical
      treatment with estradiol and genistein: a randomized double-blind controlled
      trial.
AB  - OBJECTIVE: The objective of this study is to compare the effects of topical
      estrogen and genistein (a soy isoflavone) on the facial skin collagen of
      postmenopausal women not undergoing systemic hormonal therapy. METHODS: This is a
      prospective, double blind, randomized, controlled clinical trial. Volunteer women
      (N = 30) 45-55 year old from the Endocrine Gynecology sector of the Gynecology
      Department of the Federal University of Sao Paulo (UNIFESP). The Ethical
      Committee of the Federal University of Sao Paulo approved the study (report no.
      386/2004; registration on ClinicalTrials.gov NCT01553773), were assigned to
      topical treatment with either estrogen or genistein for 24 weeks. We quantified
      and compared facial collagen concentration before and after each treatment by
      performing pre-auricular skin biopsies. RESULTS: Our data showed an increase in
      the amount of both type I and type III facial collagen by the end of both
      treatments. However, the outcomes of the estrogen GI (ER) group were superior to
      the genistein GII (GEN) group, with statistical significance p < 000.1
      Conclusion: Treatment with topical estrogen is superior to genistein, but both
      have positive impacts on facial skin collagen. Nevertheless, it is still unclear
      whether prolonged use of genistein and other topical phytoestrogens could produce
      systemic effects and further research is needed to clarify this question.

PMID- 28508698
TI  - Negative impact of litigation procedures on patient outcomes four years after
      severe traumatic brain injury: results from the PariS-traumatic brain injury
      study.
AB  - PURPOSE: To analyze the effect of litigation procedures on long-term outcomes in
      severe traumatic brain injury. MATERIALS AND METHODS: Prospective observational
      follow-up of an inception cohort including 504 adults with severe traumatic brain
      injury recruited in 2005-2007 in the Parisian area, France, with initial, one-
      and four-year outcomes measures. RESULTS: Four years after the traumatic brain
      injury, 147 patients, out of 257 who survived the acute phase, were assessed.
      Among these patients, 53 patients declared being litigants and 78 nonlitigants
      (litigation status was unknown in 16 cases). Sociodemographic characteristics,
      type of injury and initial severity did not differ significantly between
      litigants and nonlitigants, except for Injury Severity Score (worse in litigants)
      and the proportion of road traffic accidents (higher in litigants). One- and four
      year outcomes were significantly worse in litigants for autonomy, participation,
      psychiatric and cognitive function but not quality of life (measured with the
      Glasgow Outcome Scale-Extended, the working activity status, the Brain Injury
      Community Rehabilitation Outcome, the Hospital Anxiety and Depression scale, the
      Neurobehavioral Rating Scale-revised and the Quality of Life after Brain Injury,
      respectively). Multivariate analyses highlighted litigation procedure as an
      independent significant predictor of lower autonomy, participation and
      psychiatric function and tended to predict lower cognitive function, but not
      lower quality of life, after adjustment for pretrauma characteristics, Injury
      Severity Score, road traffic accidents and work-related accident status.
      CONCLUSIONS: Patients with severe traumatic brain injury have a worse prognosis
      when involved in a litigation procedure and require special attention in clinical
      practice. Implications for rehabilitation The influence of litigation procedure
      on health and social outcomes in severe traumatic brain injury is a major issue
      that entail numerous levels of complexities. A wide range of interactions and
      factors related to the prolonged process of litigation against a third party may
      influence recovery. Results from the PariS-Traumatic Brain Injury study suggest
      that patients with a severe Traumatic Brain Injury who are involved in a
      litigation procedure within French jurisdiction compensation scheme have a worse
      prognosis than patients who do not. Health professionals should be aware of the
      potential adverse effects of litigation procedures on recovery, and provide
      appropriate interventions and information to patients and families in such cases.

PMID- 28508701
TI  - Beyond 'invisibility': queer intelligibility and symbolic annihilation in
      healthcare.
AB  - Sexual minority health is increasingly receiving attention by health sciences
      education and healthcare, with the core argument being that health can be
      improved by challenging sexual minority invisibility. Invisibility as a concept,
      however, does not allow for a deeper theoretical engagement with the reasons and
      consequences of the lack of representation of queerness in healthcare. Drawing on
      empirical research with queer healthcare users in South Africa, I argue that
      'invisibility' actually encompasses two distinct, though related, concepts: queer
      symbolic annihilation as the reason for the exclusion of queer identities in
      health professions education and, by consequence, in healthcare; and queer
      (un)intelligibility as the consequence of this systemic erasure. By simply
      attributing discriminatory healthcare experiences of queer people to
      'invisibility' we are missing opportunities to address underlying issues of queer
      symbolic annihilation and unintelligibility.

PMID- 28508700
TI  - The Chronicity of Depressive Symptoms in Mothers of Children With Asthma.
AB  - Depression can disproportionately affect low-income women. The purpose of this
      study was to explore the chronicity of depressive symptoms in a sample of 276 low
      income inner-city mothers of children with high-risk asthma. The aims were to
      identify factors (asthma health status, stress, social support) associated with
      change in depressive symptomatology over 12 months as well as to ascertain what
      factors are most consistently associated with depressive symptoms. Using latent
      growth curve analysis, demographic variables, asthma severity, stress, and social
      support failed to explain changes in depressive symptomatology. The growth curve
      models, however, were predictive of Center for Epidemiologic Studies-Depression
      Scale (CES-D) scores at distinct time points indicating that higher daily stress
      and lower social support were associated with increased depressive symptoms. Our
      data highlight the chronic nature of depressive symptoms in low-income mothers of
      children with poorly controlled asthma. Integrating questions about caregiver
      psychological state across all clinical encounters with the family may be
      indicated.

PMID- 28508699
TI  - Antimicrobial, anticancer, and antioxidant compounds from Premna resinosa growing
      in Saudi Arabia.
AB  - CONTEXT: Premna resinosa (Hochst.) Schauer (Lamiaceae) is used in many places to
      treat bronchitis, respiratory illness and convulsions of the rib cage. OBJECTIVE:
      This study evaluates the anticancer, antimicrobial and antioxidant activities of
      P. resinosa, and isolates some responsible constituents. MATERIALS AND METHODS:
      The methanol extract of P. resinosa aerial parts and its fractions (n-hexane,
      dichloromethane, ethyl acetate and n-butanol) were tested. Antimicrobial activity
      was tested using microdilution method against three Gram-positive and four Gram
      negative bacteria. The tested concentrations ranged from 4000 to 7.8 MUg/mL and
      MIC values were determined after 24 h incubation. Anticancer activity was
      evaluated against three human cancer cell lines (Daoy, HepG2 and SK-MEL28) using
      MTT assay. Antioxidant activity was investigated by DPPH scavenging method and
      beta-carotene-linoleic acid assay. RESULTS: The greatest antimicrobial activity
      was exhibited by n-hexane fraction (MIC 10 MUg/mL) against Staphylococcus aureus,
      Enterococcus faecalis, and Shigella flexneri. The n-hexane fraction induced the
      greatest cytotoxic activity against Daoy, HepG2, and SK-MEL28 cell lines with
      IC50 values of 9.0, 8.5 and 13.2, respectively. Moreover, the dichloromethane and
      ethyl acetate fractions showed the highest antioxidant potential. A bioassay
      guided fractionation led to the isolation and characterization of seven compounds
      for the first time, namely, quercetin (1), 3-methoxy quercetin (2), kaempferol
      (3), 3-methoxy kaempferol (4), myricetin 3,7,3'-trimethyl ether (5), lupeol (6),
      and stigmasterol (7). CONCLUSION: Our results indicate that P. resinosa is a
      source for antimicrobial and cytotoxic compounds. However, further work is
      required to isolate other active principles and to determine the mechanism of
      action.

PMID- 28508702
TI  - Cluster Analysis in Nursing Research: An Introduction, Historical Perspective,
      and Future Directions.
AB  - The use of cluster analysis in the nursing literature is limited to the creation
      of classifications of homogeneous groups and the discovery of new relationships.
      As such, it is important to provide clarity regarding its use and potential. The
      purpose of this article is to provide an introduction to distance-based,
      partitioning-based, and model-based cluster analysis methods commonly utilized in
      the nursing literature, provide a brief historical overview on the use of cluster
      analysis in nursing literature, and provide suggestions for future research. An
      electronic search included three bibliographic databases, PubMed, CINAHL and Web
      of Science. Key terms were cluster analysis and nursing. The use of cluster
      analysis in the nursing literature is increasing and expanding. The increased use
      of cluster analysis in the nursing literature is positioning this statistical
      method to result in insights that have the potential to change clinical practice.

PMID- 28508703
TI  - Increased risk of arterial thromboembolic events with combination
      lenalidomide/dexamethasone therapy for multiple myeloma.
AB  - INTRODUCTION: Cancer associated thrombosis is a leading cause of morbidity and
      mortality. Research and guidelines have focused on venous thromboembolic events
      (VTE). Within the past decade, combination lenalidomide and dexamethasone has
      become a standard of therapy for multiple myeloma and is now widely used. In
      these patients, the risk of arterial thromboembolic events (ATE) has not been
      addressed to the same extent as VTE. Areas discussed: Presented is a targeted
      review of published data on ATE in MM patients on combination
      lenalidomide/dexamethasone therapy. Incidence, clinical presentations, prognosis,
      mechanisms and thromboprophylaxis are discussed. A framework for approaching
      ATE/VTE in these patients is suggested. Expert commentary: There is an increased
      incidence of ATE in this population, primarily cerebrovascular and cardiovascular
      events. ATE is associated with poorer prognosis and its prevention must be an
      important goal of management. It is suggested that on initiating treatment, a
      combined VTE/ATE risk assessment should be performed and thromboprophylaxis
      initiated for a minimum of 6 months. As newer immunomodulatory therapies are
      developed, thromboembolic risk must be assessed early on. Further studies are
      needed to determine the optimal strategy to reducing both VTE and ATE in this
      population.

PMID- 28508704
TI  - Differential expression of genes related to glucose metabolism in domesticated
      pigs and wild boar.
AB  - Glucose metabolism is a basic biological process that shows substantial variation
      within and between species. Using pig as a model organism, we investigated
      differences in glucose metabolic genes in seven tissues from domesticated pigs
      (Rongchang pig and Tibetan pig, meanwhile, the Tibetan pig just as a special case
      of the domesticated pig under plateau condition) and wild boar. We found large
      differences in the expression of genes involved in multiple aspects of glucose
      metabolism, including genes associated with glucose transport, gluconeogenesis,
      and glycolysis. In addition, we identified microRNAs (miRNAs) that may be
      involved in the divergence of glucose metabolism in pig. A combined analysis of
      mRNA and miRNA expression indicated that some miRNA:mRNA pairs showed ab facto
      function in it. Our results provide a valuable resource for further determination
      of miRNA regulatory roles in pig glucose metabolism and reveal the divergence of
      glucose metabolism in pigs under domestication.

PMID- 28508705
TI  - Physical demands of game-based training drills in women's team handball.
AB  - Game-based training drills are popular in team sports. This study compared two
      game-based training conditions and official matches in team handball. Thirty-one
      women players wore inertial measurement units in five training sessions and five
      official matches. In training, 3vs3 and 6vs6 game-based training conditions were
      performed with a 5-min duration. PlayerLoadTM and high-intensity events (HIEs;
      >2.5 m . s-1) were extracted from the raw data. Data were analysed using
      magnitude-based inferences and reported with effect sizes (ESs). PlayerLoadTM .
      min-1 from all positions combined was 11.37 +/- 0.49 (mean +/- 90% confidence
      limits) and 9.71 +/- 0.3 for the 3vs3 and 6vs6 conditions, respectively. Backs
      (ES: 1.63), wings (ES: 1.91), and pivots (ES: 1.58) had greater PlayerLoadTM in
      3vs3 than 6vs6. Substantially greater HIE . min-1 in 3vs3 occurred for all
      positions. There was substantially greater PlayerLoadTM . min-1 in 3vs3 and 6vs6
      than match play for backs, wings, and pivots. Wings (ES: 1.95), pivots (ES:
      0.70), and goalkeeper (ES: 1.13) had substantially greater HIE . min-1 in 3vs3
      than match play. This study shows greater PlayerLoadTM and HIE in 3vs3 than 6vs6.
      Both game-based training conditions investigated in this study provide an
      overload in overall PlayerLoadTM; however, additional exercises might be needed
      to overload HIE, especially for backs and pivots.

PMID- 28508706
TI  - British Pakistani lesbians existing within the confines of the closet.
AB  - This study explores the complex interaction between ethnicity, gender and
      [homo]sexuality and how this creates a framework of stigma that compels some
      British Pakistani lesbians to remain within the closet. The 'closet' here is a
      metaphor that describes the concealment of one's homosexual identity and the
      outward 'performance' of heterosexuality. British Pakistani lesbians precariously
      inhabit a sociocultural environment that constrains the expression of female
      sexuality. Women who oppose and contravene heteronormative values and ideals
      unsettle comfortable assumptions of heterosexuality. Being in the closet keeps
      lesbians isolated and marginalised from their ethnic and cultural communities.
      Drawing on findings from online interviews with seven British Pakistani lesbians,
      the study explores what shapes their decision to stay within the closet and how
      doing so influences their self-perception. Being in the closet is a source of
      considerable conflict, strain and anxiety, which has an impact on the women's
      readiness to embrace individual choice, freedom and desire. Findings orientate
      the reader toward an understanding of the multiple, interlocking systems of
      social relations within which British Pakistani lesbians are marginalised as the
      result of their gender, sexuality and ethnic identity.

PMID- 28508708
TI  - Erratum.

PMID- 28508707
TI  - Maternal union instability and childhood mortality risk in the Global South, 2010
      14.
AB  - Efforts to improve child survival in lower-income countries typically focus on
      fundamental factors such as economic resources and infrastructure provision, even
      though research from post-industrial countries confirms that family instability
      has important health consequences. We tested the association between maternal
      union instability and children's mortality risk in Africa, Latin America and the
      Caribbean, and Asia using children's actual experience of mortality (discrete
      time probit hazard models) as well as their experience of untreated morbidity
      (probit regression). Children of divorced/separated mothers experience
      compromised survival chances, but children of mothers who have never been in a
      union generally do not. Among children of partnered women, those whose mothers
      have experienced prior union transitions have a higher mortality risk. Targeting
      children of mothers who have experienced union instability-regardless of current
      union status-may augment ongoing efforts to reduce childhood mortality,
      especially in Africa and Latin America where union transitions are common.

PMID- 28508709
TI  - Characterisation of the biofouling community on a floating wave energy device.
AB  - Wave energy devices are novel structures in the marine environment and, as such,
      provide a unique habitat for biofouling organisms. In this study, destructive
      scrape samples and photoquadrats were used to characterise the temperate
      epibenthic community present on prototypes of the Pelamis wave energy converter.
      The biofouling observed was extensive and diverse with 115 taxa recorded
      including four non-native species. Vertical zonation was identified on the sides
      of the device, with an algae-dominated shallow subtidal area and a deeper area
      characterised by a high proportion of suspension-feeding invertebrates.
      Differences in species composition and biomass were also observed between
      devices, along the length of the device and between sampling dates. This research
      provides an insight into the variation of biofouling assemblages on a wave energy
      device as well as the potential technical and ecological implications associated
      with biofouling on marine renewable energy structures.

PMID- 28508710
TI  - Transported biofilms and their influence on subsequent macrofouling colonization.
AB  - Biofilm organisms such as diatoms are potential regulators of global macrofouling
      dispersal because they ubiquitously colonize submerged surfaces, resist
      antifouling efforts and frequently alter larval recruitment. Although ships
      continually deliver biofilms to foreign ports, it is unclear how transport shapes
      biofilm microbial structure and subsequent macrofouling colonization. This study
      demonstrates that different ship hull coatings and transport methods change
      diatom assemblage composition in transported coastal marine biofilms. Assemblages
      carried on the hull experienced significant cell losses and changes in
      composition through hydrodynamic stress, whereas those that underwent sheltered
      transport, even through freshwater, were largely unaltered. Coatings and their
      associated biofilms shaped distinct macrofouling communities and affected
      recruitment for one third of all species, while biofilms from different transport
      treatments had little effect on macrofouling colonization. These results
      demonstrate that transport conditions can shape diatom assemblages in biofilms
      carried by ships, but the properties of the underlying coatings are mainly
      responsible for subsequent macrofouling. The methods by which organisms colonize
      and are transferred by ships have implications for their distribution,
      establishment and invasion success.

PMID- 28508711
TI  - Surface sensing and stress-signalling in Ulva and fouling diatoms - potential
      targets for antifouling: a review.
AB  - Understanding the underlying signalling pathways that enable fouling algae to
      sense and respond to surfaces is essential in the design of environmentally
      friendly coatings. Both the green alga Ulva and diverse diatoms are important
      ecologically and economically as they are persistent biofoulers. Ulva spores
      exhibit rapid secretion, allowing them to adhere quickly and permanently to a
      ship, whilst diatoms secrete an abundance of extracellular polymeric substances
      (EPS), which are highly adaptable to different environmental conditions. There is
      evidence, now supported by molecular data, for complex calcium and nitric oxide
      (NO) signalling pathways in both Ulva and diatoms being involved in surface
      sensing and/or adhesion. Moreover, adaptation to stress has profound effects on
      the biofouling capability of both types of organism. Targets for future
      antifouling coatings based on surface sensing are discussed, with an emphasis on
      pursuing NO-releasing coatings as a potentially universal antifouling strategy.

PMID- 28508713
TI  - Investigation of the reasons for not using helmet among motorcyclists in Kerman,
      Iran.
AB  - This study was carried out to investigate reasoning and interpretation of
      motorcyclists for not using helmet utilizing qualitative methodology of 'grounded
      theory'. The field of the study was Kerman, a cultural-historical city at the
      south-east of Iran. Participants were 21 young male motorcyclists. Two sampling
      strategies were used: maximum variation and snowball sampling. To collect data,
      in-depth, open-ended interviews were conducted. Data analysis yielded seven
      categories: fatalism; a barrier to social relationships; peer group pressure and
      negative labelling; messing up the appearance; disturbance in hearing and vision;
      barrier to normal breathing; and heaviness and superfluity of helmet. Based on
      the findings of the current study, it could be concluded that socio-cultural
      contexts, motorcyclists' worldview and partly helmet-related problems are of the
      main factors which affect motorcycling. Therefore, the studies, policy-makings,
      and intervening programmes to control injury and to promote safety among
      motorcyclists should be focused on socio-cultural barriers to helmet use in
      general and changing the motorcyclists' standpoints toward fatalism in
      particular. Helmet-related problems should be considered, too.

PMID- 28508712
TI  - Changing Rates of Morbidity and Mortality in Obstructive Sleep Apnea Surgery.
AB  - Objective Whereas uvulopalatopharyngoplasty (UPPP) was the standard surgical
      procedure for obstructive sleep apnea prior to 2007, multilevel surgery has
      become the standard since that time. This study compares morbidity and mortality
      rates of the stand-alone UPPP with those of multilevel sleep surgery that
      includes UPPP. Methods Patients undergoing UPPP between 2007 and 2014 were
      identified in the American College of Surgeons National Surgical Quality
      Improvement Program database. UPPP was defined by Current Procedural Terminology
      codes 42145 and 42950. Primary outcomes were incidence of morbidity and
      mortality. Rates were compared between a control group with UPPP only and a group
      with multilevel surgery. Results A total of 2674 cases were analyzed. The
      incidence of complications in the UPPP-only group was 1.6% (0.09% fatal); in the
      multilevel surgery group, 4.63% (0.19% fatal). The difference in overall and
      nonfatal complications is statistically significant ( P < .01); however, values
      for fatal complications are too low for comparison. There is a statistically
      significant ( P < .01) positive correlation ( R2 = 0.92) between year of
      operation and rate of complications, with increased incidence of complications in
      more recent years. Discussion Complication rates for multilevel sleep surgery are
      higher than those of stand-alone UPPP, and overall complication rates have been
      increasing in recent years. As UPPP supplemented with multilevel surgery is now
      the standard surgical treatment for most cases of obstructive sleep apnea
      hypopnea syndrome, historical complication rates based predominantly on patients
      undergoing UPPP only underestimate complication rates of modern sleep surgery.
      Implications for Practice It is reasonable to inform patients that multilevel
      procedures bring an increased risk of complications, and patient selection should
      be guided accordingly.

PMID- 28508714
TI  - Recommendations for clinical biomarker specimen preservation and stability
      assessments.
AB  - With the wide use of biomarkers to enable critical drug-development decisions,
      there is a growing concern from scientific community on the need for a
      'standardized process' for ensuring biomarker specimen stability and hence, a
      strong desire to share best practices on preserving the integrity of biomarker
      specimens in clinical trials and the design of studies to evaluate analyte
      stability. By leveraging representative industry experience, we have attempted to
      provide an overview of critical aspects of biomarker specimen stability commonly
      encountered during clinical development, including: planning of clinical sample
      collection procedures, clinical site training, selection of sample preservation
      buffers, shipping logistics, fit-for-purpose stability assessments in the
      analytical laboratory and presentation of case studies covering widely utilized
      biomarker specimen types.

PMID- 28508715
TI  - Data and Reporting Quality in Tympanoplasty and Ossiculoplasty Studies.
AB  - Objective The objective of our study was to check the documentation of hearing
      outcome parameters and influencing factors (surgical, pathological, and
      methodological) in published literature evaluating hearing outcome after
      tympanoplasty. We aimed to assess how effectively the American Academy of
      Otolaryngology-Head and Neck Surgery (AAO-HNS) 1995 guidelines were applied.
      Study Design Retrospective noncontrolled study. Setting Ear research center.
      Subjects and Methods This study was based on a PubMed research, including peer
      reviewed English-speaking original studies published from January 2005 to
      December 2015. In total, 169 studies were checked for correct description of
      study population, surgical methodology, study design, and documentation of the
      hearing outcome. In addition, the correct application of AAO-HNS 1995 criteria
      was checked. Results Pre- and postoperative air-bone gap were shown as mean +/-
      standard deviation in half of all series (52% vs 56%). The recommended frequency
      spectrum (0.5-3 kHz) was used in 46%, while a documentation of frequency spectrum
      was available in 85%. Whereas a statement on presence of stapes suprastructure
      (81%) and initial pathology was usually available, mucosa status (17%) and
      aeration (8%) were only shown in few series. Revision cases, staged cases, and
      myringoplasty graft material were documented in 46% to 57%. Type and material of
      prosthesis were represented in 74% to 82%. None of the publications analyzed
      fulfilled all 10 AAO-HNS criteria. In 10%, 7 to 9 criteria were used correctly.
      Conclusion A heterogeneous description of surgical and pathological findings and
      the application of minimal reporting standards are essential preconditions to
      enable comparisons between different studies and to generate meta-analysis.

PMID- 28508716
TI  - Neural correlates of individual differences in fixation duration during natural
      reading.
AB  - Reading requires integration of language and cognitive processes with attention
      and eye movement control. Individuals differ in their reading ability, but little
      is known about the neurocognitive processes associated with these individual
      differences. To investigate this issue, we combined eyetracking and fMRI,
      simultaneously recording eye movements and BOLD activity while subjects read text
      passages. We found that the variability and skew of fixation duration
      distributions across individuals, as assessed by ex-Gaussian analyses, decreased
      with increasing neural activity in regions associated with the cortical eye
      movement control network (Left FEF, Left IPS, Left IFG, and Right IFG). The
      results suggest that individual differences in fixation duration during reading
      are related to underlying neurocognitive processes associated with the eye
      movement control system and its relationship to language processing. The results
      also show that eye movements and fMRI can be combined to investigate the neural
      correlates of individual differences in natural reading.

PMID- 28508717
TI  - Expanding the Haitian rehabilitation workforce: employment situation and
      perceptions of graduates from three rehabilitation technician training programs.
AB  - PURPOSE: This article examines the employment situation and perceptions of
      graduates from three rehabilitation technician (RT) programs in Haiti. METHODS:
      In this mixed method study, 74 of 93 recent graduates completed a questionnaire,
      and 20 graduates participated in an in-depth qualitative interview. We analyzed
      survey results using descriptive statistics. We used a qualitative description
      approach and analyzed the interviews using constant comparative techniques.
      RESULTS: Of the 48 survey respondents who had completed their training more than
      six months prior to completing the questionnaire, 30 had found work in the
      rehabilitation sector. Most of these technicians were working in hospitals in
      urban settings and the patient population they treated most frequently were
      patients with neurological conditions. Through the interviews, we explored the
      participants' motivations for becoming a RT, reflections on the training program,
      process of finding work, current employment, and plans for the future. An
      analysis of qualitative and quantitative findings provides insights regarding
      challenges, including availability of supervision for graduated RTs and the
      process of seeking remunerated work. CONCLUSIONS: This study highlights the need
      for stakeholders to further engage with issues related to formal recognition of
      RT training, expectations for supervision of RTs, concerns for the precariousness
      of their employment, and uncertainty about their professional futures.
      Implications for Rehabilitation The availability of human resources in the
      rehabilitation field in Haiti has increased with the implementation of three RT
      training programs over the past 10 years. RTs who found work in the
      rehabilitation sector were more likely to work in a hospital setting, in the
      province where their training had taken place, to treat a diverse patient
      clientele, and to be employed by a non-governmental organization. The study
      underlines challenges related to the long-term sustainability of RT training
      programs, as well as the employment of their graduates. Further discussion and
      research are needed to identify feasible and effective mechanisms to provide
      supervision for RTs within the Haitian healthcare system.

PMID- 28508718
TI  - Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt
      lymphoma cells.
AB  - For patients with refractory or relapsed Burkitt lymphoma (BL), no standard
      therapy is available for second-line treatment to date. Nonfunctional caspases
      dependent apoptosis pathways, inactivating p53 mutations and pro-survival
      autophagy prevent activity of conventional chemotherapy. Thus, new drugs
      bypassing these mechanisms of resistance are required. Here, we investigated the
      efficacy of the marine natural compound frondoside A (FrA) in eight BL cell
      lines. FrA revealed cytotoxic effects in all cell lines tested including the
      multiresistant CA46 cells. Remarkably, FrA induced caspases- and p53-independent
      apoptosis, which was characterized by decreased expression of antiapoptotic
      survivin and Bcl-2, mitochondria targeting (release of cytochrome C, HtrA2/Omi
      and the apoptosis-inducing factor (AIF), and altered production of ROS) and
      translocation of AIF to the nuclei. In addition, signs of inhibition of pro
      survival autophagy were observed. Thus, FrA is a promising candidate for the
      treatment of refractory or relapsed BL revealing resistances to standard
      therapies.

PMID- 28508719
TI  - Kahweol inhibits adipogenesis of 3T3-L1 adipocytes through downregulation of
      PPARgamma.
AB  - Kahweol, a compound from Coffea arabica, possesses antioxidant, anti
      inflammatory, and antitumour properties. However, an anti-adipogenic effect has
      not yet been reported. In this study, we have shown that kahweol has an anti
      adipogenic effect on 3T3-L1 adipocytes. Kahweol significantly inhibited the
      differentiation of intracellular lipid accumulation in 3T3-L1 adipocytes, without
      being cytotoxic. It also downregulated the expression of adipogenesis-related
      gene, including an adipocytokine, adiponectin. This anti-adipogenic effect stems
      from an ability to inhibit key adipogenic regulators, including PPARgamma and
      C/EBPalpha. These results demonstrate that kahweol significantly inhibits the
      differentiation of 3T3-L1 cells, and suggest that it has potential as a novel
      anti-obesity treatment.

PMID- 28508720
TI  - Human Kinematics of Cochlear Implant Surgery: An Investigation of Insertion Micro
      Motions and Speed Limitations.
AB  - Objectives Document human motions associated with cochlear implant electrode
      insertion at different speeds and determine the lower limit of continuous
      insertion speed by a human. Study Design Observational. Setting Academic medical
      center. Subjects and Methods Cochlear implant forceps were coupled to a frame
      containing reflective fiducials, which enabled optical tracking of the forceps'
      tip position in real time. Otolaryngologists (n = 14) performed mock electrode
      insertions at different speeds based on recommendations from the literature:
      "fast" (96 mm/min), "stable" (as slow as possible without stopping), and "slow"
      (15 mm/min). For each insertion, the following metrics were calculated from the
      tracked position data: percentage of time at prescribed speed, percentage of time
      the surgeon stopped moving forward, and number of direction reversals (ie, going
      from forward to backward motion). Results Fast insertion trials resulted in
      better adherence to the prescribed speed (45.4% of the overall time), no motion
      interruptions, and no reversals, as compared with slow insertions (18.6% of time
      at prescribed speed, 15.7% stopped time, and an average of 18.6 reversals per
      trial). These differences were statistically significant for all metrics ( P <
      .01). The metrics for the fast and stable insertions were comparable; however,
      stable insertions were performed 44% slower on average. The mean stable insertion
      speed was 52 +/- 19.3 mm/min. Conclusion Results indicate that continuous
      insertion of a cochlear implant electrode at 15 mm/min is not feasible for human
      operators. The lower limit of continuous forward insertion is 52 mm/min on
      average. Guidelines on manual insertion kinematics should consider this practical
      limit of human motion.

PMID- 28508721
TI  - Acute renal failure with need for renal replacement therapy as a complication of
      zoonotic S. zooepidemicus infection: case report and review of the literature.
AB  - Streptococcus zooepidemicus is an animal commensal with the potential of zoonotic
      transmission through ingestion of contaminated dairy products, leading to
      outbreaks of Post-Streptococcal Glomerulonephritis (PSGN). We report for the
      first time acute renal failure with need for renal replacement therapy, as a
      complication of S. zooepidemicus bacteremia resulting from direct horse to human
      transmission in a young adult. Both clinical disease course and
      immunohistochemical staining patterns on renal biopsy had some atypical features
      of PSGN suggesting persistent activation of the alternative complement pathway
      but no known complement factor dysregulations could be identified.

PMID- 28508722
TI  - A Natural History of the Drag Queen Phenomenon.
AB  - The drag queen cultural phenomenon has been described at length. However, the
      depiction of outlandish and hyperbolic womanhood and taunting and formidable
      behavior at the core of drag queens' public persona has still to be fully
      accounted for. We argue that these aspects of the drag queen's public appearance
      could best be understood in a signaling framework. Publicly donning extravagant
      woman's costumes attracts harassment and brings financial, mating, and
      opportunity costs, generating the conditions for the transmission of honest
      signals. By successfully withstanding those odds, drag queen impersonators signal
      strategic qualities to members of the gay community. Data collected among gay and
      straight participants support a costly signaling reading of the drag queen
      cultural phenomenon. Participants generally agree that successful drag queens
      typically incur costs, while gaining specific social benefits.

PMID- 28508723
TI  - Drinking High Amounts of Alcohol as a Short-Term Mating Strategy: The Impact of
      Short-Term Mating Motivations on Young Adults' Drinking Behavior.
AB  - Previous research indicates that drinking large quantities of alcohol could
      function as a short-term mating strategy for young adults in mating situations.
      However, no study investigated whether this is actually the case. Therefore, in
      this article, the link between short-term mating motivations and drinking high
      amounts of alcohol is tested. First, a survey study ( N = 345) confirmed that
      young adults who engage in binge drinking are more short-term oriented in their
      mating strategy than young adults who never engage in binge drinking. Also, the
      more short-term-oriented young adults were in their mating strategy, the more
      often binge drinking behavior was conducted. In addition, an experimental study (
      N = 229) empirically verified that short-term mating motivations increase young
      adults' drinking behavior, more so than long-term mating motivations. Results of
      the experiment clearly showed that young men and young women are triggered to
      drink more alcoholic beverages in a short-term mating situation compared to a
      long-term mating situation. Furthermore, the mating situation also affected young
      adults' perception of drinking behavior. Young adults in a short-term mating
      context perceived a higher amount of alcoholic beverages as heavy drinking
      compared to peers in a long-term mating context. These findings confirm that a
      high alcohol consumption functions as a short-term mating strategy for both young
      men and young women. Insights gained from this article might be of interest to
      institutions aimed at targeting youth alcohol (ab)use.

PMID- 28508724
TI  - The impact of simulated motion blur on lesion detection performance in full-field
      digital mammography.
AB  - OBJECTIVE: Motion blur is a known phenomenon in full-field digital mammography,
      but the impact on lesion detection is unknown. This is the first study to
      investigate detection performance with varying magnitudes of simulated motion
      blur. METHODS: 7 observers (15 +/- 5 years' reporting experience) evaluated 248
      cases (62 containing malignant masses, 62 containing malignant
      microcalcifications and 124 normal cases) for 3 conditions: no blurring (0 mm)
      and 2 magnitudes of simulated blurring (0.7 and 1.5 mm). Abnormal cases were
      biopsy proven. Mathematical simulation was used to provide a pixel shift in order
      to simulate motion blur. A free-response observer study was conducted to compare
      lesion detection performance for the three conditions. The equally weighted
      jackknife alternative free-response receiver operating characteristic was used as
      the figure of merit. Test alpha was set at 0.05 to control probability of Type I
      error. RESULTS: The equally weighted jackknife alternative free-response receiver
      operating characteristic analysis found a statistically significant difference in
      lesion detection performance for both masses [F(2,22) = 6.01, p = 0.0084] and
      microcalcifications [F(2,49) = 23.14, p < 0.0001]. The figures of merit reduced
      as the magnitude of simulated blurring increased. Statistical differences were
      found between some of the pairs investigated for the detection of masses (0.0 vs
      0.7 and 0.0 vs 1.5 mm) and all pairs for microcalcifications (0.0 vs 0.7, 0.0 vs
      1.5 and 0.7 vs 1.5 mm). No difference was detected between 0.7 and 1.5 mm for
      masses. CONCLUSION: The mathematical simulation of motion blur caused a
      statistically significant reduction in lesion detection performance. These false
      negative decisions could have implications for clinical practice. Advances in
      knowledge: This research demonstrates for the first time that motion blur has a
      negative and statistically significant impact on lesion detection performance in
      digital mammography.

PMID- 28508725
TI  - Evaluating change in virtual reality adoption for brain injury rehabilitation
      following knowledge translation.
AB  - PURPOSE: To evaluate the impact of knowledge translation (KT) on factors
      influencing virtual reality (VR) adoption and to identify support needs of
      therapists. HYPOTHESES: Intervention will be associated with improvements in
      therapists' perceived ease of use and self-efficacy, and an associated increase
      in intentions to use VR. METHOD: Single group mixed-methods pre-test-post-test
      evaluation of convenience sample of physical, occupational and rehabilitation
      therapists (n=37) from two brain injury rehabilitation centres. ADOPT-VR
      administered pre/post KT intervention, consisting of interactive education,
      clinical manual, technical and clinical support. RESULTS: Increases in perceived
      ease of use (p=0.000) and self-efficacy (p=0.001), but not behavioural intention
      to use VR (p=0.158) were found following KT, along with decreases in the
      frequency of perceived barriers. Post-test changes in the frequency and nature of
      perceived facilitators and barriers were evident, with increased emphasis on peer
      influence, organisational-level supports and client factors. Additional support
      needs were related to clinical reasoning, treatment programme development,
      technology selection and troubleshooting. CONCLUSIONS: KT strategies hold
      potential for targeting therapists' perceptions of low self-efficacy and ease of
      use of this technology. Changes in perceived barriers, facilitators and support
      needs at post-test demonstrated support for repeated evaluation and multi-phased
      training initiatives to address therapists' needs over time. Implications for
      Rehabilitation Therapists' learning and support needs in integrating virtual
      reality extend beyond technical proficiency to include clinical decision-making
      and application competencies spanning the entire rehabilitation process. Phased,
      multi-faceted strategies may be valuable in addressing therapists' changing needs
      as they progress from novice to experienced virtual reality users. The ADOPT-VR
      is a sensitive measure to re-evaluate the personal, social, environmental,
      technology-specific and system-level factors influencing virtual reality adoption
      over time.

PMID- 28508726
TI  - Does the Timing of Middle Turbinate Resection Influence Quality-of-Life Outcomes
      for Patients with Chronic Rhinosinusitis?
AB  - Objective To evaluate the impact of bilateral middle turbinate resection (BMTR)
      on patient-reported quality of life following primary and revision endoscopic
      sinus surgery (ESS) for chronic rhinosinusitis (CRS). Study Design Prospective
      cohort study. Setting Tertiary care center. Subjects and Methods Patients with
      CRS who were recruited from 11 otolaryngologic practices completed the Sino-Nasal
      Outcome Test-22, Chronic Sinusitis Survey, and EuroQol 5-Dimension questionnaires
      at baseline, as well as 3 and 12 months after ESS. In the primary ESS cohort (n =
      406), patients who underwent BMTR (n = 78) at the time of surgery were compared
      with patients (n = 328) whose middle turbinates were preserved. In the revision
      ESS cohort (n = 363), a similar comparison was made between patients who did (n =
      64) and did not (n = 299) undergo BMTR. Results Sino-Nasal Outcome Test-22,
      Chronic Sinusitis Survey, and EuroQol 5-Dimension scores showed similar
      improvements for both the turbinate resection and preservation cohorts at 3
      months ( P < .001) and 12 months ( P < .001) after surgery. For patients who
      underwent revision surgery, the performance of BMTR resulted in greater
      improvement in Chronic Sinusitis Survey scores at 1 year as compared with the
      turbinate preservation group (change from baseline: 28.1 vs 20.7, respectively; P
      = .026). History of tobacco use and the presence of nasal polyps did not affect
      clinical outcomes at any time point. Conclusion Patients who underwent BMTR
      during primary and revision sinus surgery reported similar benefits in quality-of
      life outcomes 1 year after surgery. In select patients undergoing revision sinus
      surgery, the performance of BMTR results in improved disease-specific quality of
      life.

PMID- 28508729
TI  - Disciplinary action against solicitors and the role of the Solicitors
      Disciplinary Tribunal.

PMID- 28508727
TI  - The role of Wnt signaling in hematopoietic stem cell development.

PMID- 28508728
TI  - High frequency of identical clonal immunoglobulin DNA in pre-treatment tumor and
      plasma from untreated patients with HIV-associated lymphoma: prospective
      multicenter trial of the AIDS malignancies consortium (AMC 064).
AB  - Patients with HIV are at increased risk for developing B-cell lymphomas likely
      due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig)
      gene rearrangements. Next-generation sequencing (NGS)-based identification of
      circulating Ig clonotypes has not been well-characterized in HIV-related
      lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients
      with HIV-related B-cell lymphomas and analyzed paired tumor/plasma specimens for
      Ig clonotypes using an NGS approach (AMC064, NCT00981097). Lymphoma-specific
      clonotypes (>5% frequency) were identified in 83% (33/40) of tumor specimens.
      Results from paired tumor/plasma specimens showed identical circulating
      clonotypes in the plasma from 97% (32/33) of patients. High International
      Prognostic Index (IPI) scores of 3-4 among patients with B-cell lymphoma
      correlated with higher lymphoma molecules/million diploid genomes in the plasma
      compared with lower IPI scores of 0-2, median 77335 vs. 6876, p = .005. Further
      studies are merited to determine whether plasma clonal Ig DNA is prognostic in
      HIV-related lymphomas.

PMID- 28508731
TI  - Submitting medico-legal intra-partum CTG (I-P CTG) monitoring to the Bolam and
      Bolitho principles.
AB  - The article analyses some of the seeming weaknesses of the Bolam and Bolitho
      tests as applied to electronic foetal monitoring in labour, in the form of intra
      partum CTG monitoring. Homing on to such aspects as confirmation of foetal
      hypoxia/acidosis, it evaluates the Bolam and Bolitho tests in the context of
      evidence-based medicine versus traditionally held views, which still hold their
      own in medical jurisprudence. Case law examples are quoted to illustrate various
      points. The discussion is of practical relevance both to the individual
      obstetrician as well as to national budgetary implications, bearing in mind,
      that, for example, in 2011, 'birth asphyxia' comprised 50% of the UK NHS
      litigation costs, and in the 2000-2010 decade, the same NHS forked out L3.1
      billion for maternity medico-legal claims (the highest of any speciality), mostly
      involving cerebral palsy and CTG misinterpretation. The article concludes with
      suggestions to help level the potential extant equivocity between legal principle
      and medical practice. It also looks at the ruling in Montgomery v Lanarkshire
      Health Board, UK Supreme Court, and its challenge to Bolam. The implications pose
      a serious and overdue challenge to a test, born in 1957 and lacking the necessary
      qualities to serve many 21st century medical quandaries, including the ones
      raised here.

PMID- 28508732
TI  - Editorial.

PMID- 28508730
TI  - A rare fatality due to calcified stylohyoid ligament (Eagle syndrome).
AB  - The elongation or calcification of the stylohyoid ligament that leads to pressure
      symptoms, or entrapment of nearby glossopharyngeal nerve or carotid artery, is
      known as Eagle syndrome. A PubMed search leads to finding of rare fatality among
      the 49 reported cases. In the present case, the deceased was a 40-year-old male
      who choked on his food. We hypothesise that the impaction of food in the upper
      respiratory tract, as well as the inability to intubate the person, were both the
      result of the calcified stylohyoid ligament.

PMID- 28508733
TI  - Synthesis of aurachins B and H.
AB  - The synthesis of aurachin B, an antibiotic that features a C3-oxygen-substituted
      quinoline N-oxide nucleus bearing a farnesyl side chain at C4, was accomplished
      in 60% overall yield from o-nitrotoluene by a concise five-step sequence. An
      enantioselective synthesis of aurachin H was also achieved for the first time in
      only two steps from an optically active epoxy iodide.

PMID- 28508734
TI  - The role of cue utilisation in reducing the workload in a train control task.
AB  - Skilled performance has been characterised, in part, by the capacity to
      accurately identify and respond to patterns as cues in the environment. The
      outcome is a reduction in cognitive load and a greater residual capacity to
      undertake concurrent tasks. The present study was designed to examine the
      relationship between cue utilisation and temporal pattern recognition in the
      context of a simulated, rail control task. Sixty-one university students
      undertook an assessment of cue utilisation and engaged in a rail control
      simulation. The appearance and movement of trains followed a consistent but
      implicit (undisclosed) pattern. Throughout the second half of the rail task, a
      secondary task was included. The results indicated that participants with
      relatively higher cue utilisation were more likely to identify the implicit
      pattern of rail movements, were more accurate and responded more rapidly under
      increased workload conditions. The results suggest that a propensity to identify
      patterns as cues may provide an opportunity to reduce cognitive demands, thereby
      facilitating performance in a novel task. Implications for selection and system
      design are discussed. Practitioner Summary: This study was designed to explain
      differences in the way in which people learn, particularly when tasks involve
      recurring patterns. Using simulated rail control, the results indicated that
      participants who display behaviour that is indicative of the utilisation of cues
      also recognise patterns in the movement of simulated trains. This enables them to
      manage trains more effectively, even while undertaking other tasks.

PMID- 28508735
TI  - Sleep problems in breast cancer survivors 1-10 years posttreatment.
AB  - : ABSTRACTObjective:Sleep can affect quality of life (QoL) during cancer
      survivorship, and symptoms related to poor sleep can be exacerbated. We examined
      the prevalence, severity, and nature of subjective sleep complaints in women
      surviving stage I-III breast cancer who were 1-10 years posttreatment. We also
      examined the demographic, medical, physical, and psychosocial correlates of poor
      sleep in these women in order to identify the subgroups that may be most in need
      of intervention. METHOD: A total of 200 patients at a comprehensive cancer center
      who were 1-10 years posttreatment for primary stage I-III breast cancer with no
      evidence of disease at the time of enrollment completed a battery of
      questionnaires on demographics, sleep, physical symptoms, mood, cancer-specific
      fears, and QoL. RESULTS: The women had a mean age of 57 years (SD = 10.0), with a
      mean of 63.3 months (SD = 28.8) of post-cancer treatment. Some 38% of these
      patients were identified as having poor-quality sleep. Women with poor sleep took
      longer to fall asleep, had more awakenings, and acquired 2 hours less sleep per
      night than those with good sleep. They also had a lower QoL, greater severity of
      pain, more concerns about health and recurrence, and increased vasomotor symptoms
      (p < 0.05). Daytime sleepiness and depression were found to be not significantly
      correlated with sleep quality. SIGNIFICANCE OF RESULTS: Many breast cancer
      survivors had severe subjective insomnia, and several breast cancer survivor
      subgroups were identified as having members who might be most in need of sleep
      improvement interventions. Addressing physical symptoms (e.g., vasomotor symptoms
      and pain) and providing education about the behavioral, social, environmental,
      and medical factors that affect sleep could result in substantial improvement in
      the life course of breast cancer survivors.

PMID- 28508736
TI  - Out of harm's way: Secure versus insecure-disorganized attachment predicts less
      adolescent risk taking related to childhood poverty.
AB  - Although some risk taking in adolescence is normative, evidence suggests that
      adolescents raised in conditions of socioeconomic disadvantage are
      disproportionately burdened with risk taking and its negative consequences. Using
      longitudinal data from the NICHD Study of Early Child Care and Youth Development,
      we investigated quality of the early caregiving environment as a potential
      prospective buffer against the long-term association between childhood poverty
      and adolescent risk taking. Multicategorical moderation model results indicated
      that if raised in poverty across age 1-54 months (average family income to needs
      ratio <= 1.02), relative to affluence (income to needs ratio >= 6.16),
      adolescents with histories of secure attachment to caregivers exhibited two times
      the number of risk behaviors at age 15, whereas adolescents with insecure
      disorganized histories exhibited nearly five times the number of risk behaviors.
      Both early family economic hardship and history of insecure-disorganized
      attachment remained significant predictors of increased adolescent risk taking,
      alongside the interactive effect. Probing the interaction's region of
      significance revealed that history of secure (vs. insecure-disorganized)
      attachment is associated with protective reductions in risk taking below a family
      income to needs ratio of 2.24, or about 220% poverty level. Findings support a
      diathesis-stress model in which children with secure attachment histories are
      less deleteriously impacted by early socioeconomic adversity than their insecure
      disorganized peers.

PMID- 28508737
TI  - The future for long chain n-3 PUFA in the prevention of coronary heart disease:
      do we need to target non-fish-eaters?
AB  - Dietary guidelines in many countries include a recommendation to consume oily
      fish, mainly on the basis of evidence from prospective cohort studies that fish
      consumption is cardioprotective. However, average intakes are very low in a large
      proportion of the UK population. Some groups, such as vegans and vegetarians,
      purposely omit fish (along with meat) from their diet resulting in zero or trace
      intakes of long chain (LC) n-3 PUFA. Although the efficacy of dietary fish oil
      supplementation in the prevention of CVD has been questioned in recent years, the
      balance of evidence indicates that LC n-3 PUFA exert systemic pleiotropic effects
      through their influence on gene expression, cell signalling, membrane fluidity
      and by conversion to specialised proresolving mediators; autacoid lipid mediators
      that resolve inflammatory events. The long-term impact of reduced tissue LC n-3
      PUFA content on cardiovascular health is surprisingly poorly understood,
      particularly with regard to how low proportions of LC n-3 PUFA in cell membranes
      may affect cardiac electrophysiology and chronic inflammation. Randomised
      controlled trials investigating effects of supplementation on prevention of CHD
      in populations with low basal LC n-3 PUFA tissue status are lacking, and so the
      clinical benefits of supplementing non-fish-eating groups with vegetarian sources
      of LC n-3 PUFA remain to be determined. Refocusing dietary LC n-3 PUFA
      intervention studies towards those individuals with a low LC n-3 PUFA tissue
      status may go some way towards reconciling results from randomised controlled
      trials with the epidemiological evidence.

PMID- 28508738
TI  - Social-ecological predictors of externalizing behavior trajectories in at-risk
      youth.
AB  - Extant research consistently links youth externalizing problems and later
      maladaptive outcomes, and these behaviors are particularly detrimental given
      their relative stability across development. Although an array of risk and
      protective factors for externalizing problems have been identified, few studies
      have examined factors reflecting the multiple social-ecological levels that
      influence child development and used them to predict longitudinal trajectories of
      externalizing problems. The current study examined externalizing behavior
      trajectories in a sample of 1,094 at-risk youth (539 boys, 555 girls) from the
      Longitudinal Studies in Child Abuse and Neglect multisite longitudinal study of
      child maltreatment. Normed Child Behavior Checklist externalizing scores were
      used to estimate group trajectories via growth-based trajectory modeling at ages
      10, 12, 14, and 16 using the SAS PROC TRAJ procedure. Model fit was assessed
      using the Bayes information criterion and the Akaike information criterion
      statistics. Analyses revealed optimal fit for five distinct behavioral
      trajectories: low stable, mid-increasing, mid-decreasing, medium high, and high
      stable. Multinomial logistic regressions revealed that a combination of risk and
      protective factors at individual, family, school, and neighborhood levels
      contribute to distinct trajectories of externalizing problems over time.
      Predictors of low and decreasing trajectories can inform interventions aimed at
      addressing externalizing problems among high-risk adolescents.

PMID- 28508739
TI  - The effects of supportive care interventions on depressive symptoms among
      patients with lung cancer: A metaanalysis of randomized controlled studies.
AB  - OBJECTIVE: Our aim was to examine the effect of supportive care interventions on
      depressive symptoms in patients with lung cancer. METHOD: We searched the
      databases of the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid
      EMBASE, PubMed, and the Chinese Electronic Periodical Services (CEPS) from their
      inception until September of 2015. We included randomized controlled trial
      studies that compared standard care with supportive care interventions. The
      standardized mean difference (SMD) (Cohen's d) was calculated to estimate the
      effect of interventions. Subgroup analysis was conducted to identify possible
      sources of heterogeneity. RESULTS: A total of 1,472 patients with lung cancer
      were identified. Compared with standard care, the overall effects of all
      supportive care interventions significantly reduced depressive symptoms (SMD = 
      0.74, CI 95% = -1.07 to -0.41), and the effects could be maintained at weeks 4,
      8, and 12 of follow-up. Three types of supportive care interventions were
      identified: psychotherapy combined with psychoeducation, psychoeducation alone,
      and an exercise program. Both psychotherapy combined with psychoeducation and
      exercise significantly improved depressive symptoms, while psychoeducation alone
      did not yield significant effects. The moderating effects indicated that greater
      improvements in depressive symptoms were found in lung cancer patients with a
      severe level of depressive symptoms at baseline. SIGNIFICANCE OF RESULTS:
      Personalized supportive care interventions can be developed based on the main
      causes of depressive symptoms. Psychotherapy combined with psychoeducation can
      target the causes of depressive symptoms, including both physical distress and
      psychological trauma due to lung cancer, while exercise programs can effectively
      improve depressive symptoms for lung cancer patients with impaired respiratory
      function.

PMID- 28508740
TI  - CAEP 2016 Academic Symposium: A Writer's Guide to Key Steps in Producing Quality
      Medical Education Scholarship.
AB  - A key skill for successful clinician educators is the effective dissemination of
      scholarly innovations and research. Although there are many ways to disseminate
      scholarship, the most accepted and rewarded form of educational scholarship is
      publication in peer-reviewed journals. This paper provides direction for
      emergency medicine (EM) educators interested in publishing their scholarship via
      traditional peer-reviewed avenues. It builds upon four literature reviews that
      aggregated recommendations for writing and publishing high-quality quantitative
      and qualitative research, innovations, and reviews. Based on the findings from
      these literature reviews, the recommendations were prioritized for importance and
      relevance to novice clinician educators by a broad community of medical
      educators. The top items from the expert vetting process were presented to the
      2016 Canadian Association of Emergency Physicians (CAEP) Academic Symposium
      Consensus Conference on Education Scholarship. This community of EM educators
      identified the highest yield recommendations for junior medical education
      scholars. This manuscript elaborates upon the top recommendations identified
      through this consensus-building process.

PMID- 28508741
TI  - CAEP 2016 Academic Symposium on Education Scholarship: Training our Future
      Clinician Educators in Emergency Medicine.
AB  - OBJECTIVE: To develop consensus recommendations for training future clinician
      educators (CEs) in emergency medicine (EM). METHODS: A panel of EM education
      leaders was assembled from across Canada and met regularly by teleconference over
      the course of 1 year. Recommendations for CE training were drafted based on the
      panel's experience, a literature review, and a survey of current and past EM
      education leaders in Canada. Feedback was sought from attendees at the Canadian
      Association of Emergency Physicians (CAEP) annual academic symposium.
      Recommendations were distributed to the society's Academic Section for further
      feedback and updated by a consensus of the expert panel. RESULTS: Recommendations
      were categorized for one of three audiences: 1) Future CEs; 2) Academic
      departments and divisions (AD&D) that support training to fulfill their education
      leadership goals; and 3) The CAEP Academic Section. Advanced medical education
      training is recommended for any emergency physician or resident who pursues an
      education leadership role. Individuals should seek out mentorship in making
      decisions about career opportunities and training options. AD&D should regularly
      perform a needs assessment of their future CE needs and identify and encourage
      potential individuals who fulfill education leadership roles. AD&D should develop
      training opportunities at their institution, provide support to complete this
      training, and advocate for the recognition of education scholarship in their
      institutional promotions process. The CAEP Academic Section should support
      mentorship of future CEs on a national scale. CONCLUSION: These recommendations
      serve as a framework for training and supporting the next generation of Canadian
      EM medical educators.

PMID- 28508742
TI  - CAEP 2016 Academic Symposium: How to have an impact as an emergency medicine
      educator and scholar.
AB  - BACKGROUND: In a time of major medical education transformation, emergency
      medicine (EM) needs to nurture education scholars who will influence EM education
      practice. However, the essential ingredients to ensure a career with impact in EM
      education are not clear. OBJECTIVE: To describe how to prepare EM educators for a
      high-impact career. METHODS: The Canadian Association of Emergency Physicians
      (CAEP) Academic Section commissioned an "Education Impact" working group (IWG) to
      guide the creation of consensus recommendations from the EM community. EM
      educators from across Canada were initially recruited from the networks of the
      IWG members, and additional educators were recruited via snowball sampling. "High
      impact educators" were nominated by this network. The high impact educators were
      then interviewed using a structured question guide. These interviews were
      transcribed and coded for themes using qualitative methods. The process continued
      until no new themes were identified. Proposed themes and recommendations were
      presented to the EM community at the CAEP 2016 Academic Symposium. Feedback was
      then incorporated into a final set of recommendations. RESULTS: Fifty-five (71%)
      of 77 of identified Canadian EM educators participated, and 170 names of high
      impact educators were submitted and ranked by frequency. The IWG achieved
      sufficiency of themes after nine interviews. Five recommendations were made: 1)
      EM educators can pursue a high impact career by leveraging either traditional or
      innovative career pathways; 2) EM educators starting their education careers
      should have multiple senior mentors; 3) Early-career EM educators should immerse
      themselves in their area of interest and cultivate a community of practice, not
      limited to EM; 4) Every academic EM department and EM teaching site should have
      access to an EM educator with protected time and recognition for their EM
      education scholarship; and 5) Educators at all stages should continuously compile
      an impact portfolio. CONCLUSIONS: We describe a unique set of recommendations to
      develop educators who will influence EM, derived from a consensus from the EM
      community. EM leaders, educators, and aspiring educational scholars should
      consider how to implement this guide towards enhancing our specialty's
      educational mission.

PMID- 28508744
TI  - Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial
      Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer
      Cells.
AB  - The human papillomavirus (HPV) infection may be associated with the development
      and progression of non-small cell lung cancer (NSCLC). However, the role of HPV
      16 oncoproteins in the development and progression of NSCLC is not completely
      clear. Epithelial-mesenchymal transition (EMT), a crucial step for invasion and
      metastasis, plays a key role in the development and progression of NSCLC. Here we
      explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms.
      NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP
      N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were
      performed to analyze the expression of EMT markers. A protein microarray was used
      to screen the involved signaling pathway. Our results showed that overexpression
      of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted EMT-like
      morphologic changes, downregulated the mRNA and protein levels of EMT epithelial
      markers (E-cadherin and ZO-1), and upregulated the mRNA and protein levels of EMT
      mesenchymal markers (N-cadherin and vimentin) and transcription factors (ZEB-1
      and Snail-1). Furthermore, the HPV-16 E6 oncoprotein promoted STAT3 activation.
      Moreover, WP1066, a specific signal transducer and activator of transcription 3
      (STAT3) inhibitor, reversed the effect of HPV-16 E6 on the expression of ZO-1,
      vimentin, and ZEB-1 in transfected NSCLC cells. Taken together, our results
      suggest that overexpression of HPV-16 E6 and E7 oncoproteins enhances EMT, and
      the STAT3 signaling pathway may be involved in HPV-16 E6-induced EMT in NSCLC
      cells.

PMID- 28508745
TI  - Natural Leishmania (Viannia) infections of phlebotomines (Diptera: Psychodidae)
      indicate classical and alternative transmission cycles of American cutaneous
      leishmaniasis in the Guiana Shield, Brazil.
AB  - From 1996 to 1999 multi-trapping methods (Center of Diseases Control, CDC) light
      traps, light-baited Shannon traps, and aspiration on tree bases) were used to
      study the phlebotomine fauna of the "Serra do Navio" region of the Brazilian
      State of Amapa, which is part of the Guiana Shield. Fifty-three species were
      identified among 8,685 captured individuals. The following species, associated
      with the transmission of American cutaneous leishmaniasis in Amazonian Brazil,
      were captured: Nyssomyia umbratilis (3,388), Psychodopygus squamiventris
      maripaensis (995), Ny. anduzei (550), Trichophoromyia ubiquitalis (400), Ny.
      whitmani (291), Ps. paraensis (116), and Bichromomyia flaviscutellata (50).
      Flagellate infections were detected in 45 flies. Of the 19 parasites isolated in
      vitro, 15 were Leishmania (Viannia) guyanensis (13 in Ny. umbratilis, 1 in Ny.
      whitmani, 1 in Ny. anduzei) and three were L. (V.) naiffi (2 in Ps. s.
      maripaensis, 1 in Ny. anduzei). The results indicate the participation of three
      phlebotomine species in the transmission of L. (V.) guyanensis and two species in
      that of L. (V.) naiffi, and show that the same phlebotomine species is involved
      in the transmission of different Leishmania (Viannia) species in the
      Guianan/Amazon region. A review of the literature together with the results of
      the present study, and other published and unpublished results, indicate that
      eight phlebotomine species potentially participate in the transmission of
      Leishmania (Viannia) naiffi in Amazonia.

PMID- 28508746
TI  - Ciliomotor circuitry underlying whole-body coordination of ciliary activity in
      the Platynereis larva.
AB  - Ciliated surfaces harbouring synchronously beating cilia can generate fluid flow
      or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes
      in beat frequency are often coordinated across extended or discontinuous
      surfaces. To understand how such coordination is achieved, we studied the
      ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae
      have segmental multiciliated cells that regularly display spontaneous coordinated
      ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis,
      and neuron ablation to characterize the ciliomotor circuitry. We identified
      cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The
      synchronous rhythmic activation of cholinergic cells drives the coordinated
      arrests of all cilia. The serotonergic cells are active when cilia are beating.
      Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency.
      Based on their connectivity and alternating activity, the catecholaminergic cells
      may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go
      pacemaker system for the whole-body coordination of ciliary locomotion.

PMID- 28508747
TI  - Voltage-gated Na+ currents in human dorsal root ganglion neurons.
AB  - Available evidence indicates voltage-gated Na+ channels (VGSCs) in peripheral
      sensory neurons are essential for the pain and hypersensitivity associated with
      tissue injury. However, our understanding of the biophysical and pharmacological
      properties of the channels in sensory neurons is largely based on the study of
      heterologous systems or rodent tissue, despite evidence that both expression
      systems and species differences influence these properties. Therefore, we sought
      to determine the extent to which the biophysical and pharmacological properties
      of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp
      techniques were used to study Na+ currents in acutely dissociated neurons from
      human and rat. Our results indicate that while the two major current types,
      generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were
      qualitatively similar in neurons from rats and humans, there were several
      differences that have important implications for drug development as well as our
      understanding of pain mechanisms.

PMID- 28508749
TI  - Diagnostic properties of provocation tests for cold, heat, and delayed-pressure
      urticaria.

PMID- 28508750
TI  - A case of basal cell carcinoma with a neighbouring melanocytic nevus: dermoscopic
      features.

PMID- 28508751
TI  - The value of teledermatology using a mobile app compared to conventional
      dermatology.

PMID- 28508752
TI  - Nail toxicities induced by liposomal doxorubicin: a retrospective case series.

PMID- 28508748
TI  - Macrophages are necessary for epimorphic regeneration in African spiny mice.
AB  - How the immune system affects tissue regeneration is not well understood. In this
      study, we used an emerging mammalian model of epimorphic regeneration, the
      African spiny mouse, to examine cell-based inflammation and tested the hypothesis
      that macrophages are necessary for regeneration. By directly comparing
      inflammatory cell activation in a 4 mm ear injury during regeneration (Acomys
      cahirinus) and scarring (Mus musculus), we found that both species exhibited an
      acute inflammatory response, with scarring characterized by stronger
      myeloperoxidase activity. In contrast, ROS production was stronger and more
      persistent during regeneration. By depleting macrophages during injury, we
      demonstrate a functional requirement for these cells to stimulate regeneration.
      Importantly, the spatial distribution of activated macrophage subtypes was unique
      during regeneration with pro-inflammatory macrophages failing to infiltrate the
      regeneration blastema. Together, our results demonstrate an essential role for
      inflammatory cells to regulate a regenerative response.

PMID- 28508753
TI  - Endometriosis in the setting of Muckle-Wells syndrome treated with an IL-1beta
      antagonist.

PMID- 28508754
TI  - Postoperative maxillary cyst presenting as a skin tumour on the cheek.

PMID- 28508755
TI  - Desmoplastic fibroblastoma: an unusual dermal presentation on the buttock of a
      patient with muscular dystrophy.

PMID- 28508756
TI  - A solid variant of primary cutaneous cribriform carcinoma: a small, stable, long
      term lesion.

PMID- 28508757
TI  - Unilateral nevoid telangiectasia: a condition unmasked by hyperoestrogenism?

PMID- 28508758
TI  - Cutaneous larva migrans: a case in Bordeaux, France and a systematic review of
      locally acquired cases in Europe.

PMID- 28508759
TI  - MRI-TRUS fusion for electrode positioning during irreversible electroporation for
      treatment of prostate cancer.
AB  - We aimed to introduce an approach for image-guided positioning of electrodes for
      irreversible electroporation (IRE) in patients with prostate cancer using a
      magnetic resonance imaging-transrectal ultrasonography (MRI-TRUS) fusion
      technique. In 10 consecutive patients with biopsy-proven Gleason score <=3+4
      prostate cancer, 19 G electrodes were inserted into the prostate using a
      transperineal access. Magnetic resonance images of the prostate acquired before
      IRE were fused with transrectal ultrasound images acquired during IRE. The
      position of the ultrasound probe was tracked via a sensor and corresponding
      magnetic resonance images were calculated in real-time. While MRI allowed
      delineation of the target volume, the position of the electrodes could be
      visualized on ultrasound images; the distance between individual electrode pairs
      was measured. Based on these measurements the software installed on the IRE unit
      was able to calculate the voltage necessary to generate the electric field for
      ablation. Using contrast-enhanced ultrasound, changes in perfusion within the
      ablation zone after IRE were documented. This technique allowed positioning of
      the electrodes around the target volume under image guidance in all patients
      treated with IRE. The target lesion and a safety margin were covered within the
      estimated ablation zone. MRI-TRUS guidance for IRE combines the advantages of
      good visualization of the target lesion on MRI with the ability of ultrasound to
      acquire imaging in real-time with a mobile device.

PMID- 28508760
TI  - Radiologic and histopathologic review of rare benign and malignant breast
      diseases.
AB  - High social awareness of breast diseases and the rise in breast imaging
      facilities have led to an increase in the detection of even rare benign and
      malignant breast lesions. Breast lesions are associated with a broad spectrum of
      imaging characteristics, and each radiologic imaging technique reflects different
      characteristics of them. We aimed to increase familiarity of the radiologist with
      these uncommon lesions as well as correlate histopathologic findings with the
      radiologic imaging features of the tumors. Histopathologic examination is
      necessary in the evaluation of such breast lesions, particularly when radiologic
      images are not definitive for a specific diagnosis.

PMID- 28508761
TI  - Posterior Branches of Lumbar Spinal Nerves - part II: Lumbar Facet Syndrome -
      Pathomechanism, Symptomatology and Diagnostic Work-up.
AB  - Posterior branches of the lumbar spinal nerves are the anatomic substrate of pain
      in the lower back, sacrum and the gluteal area. Such pain may be associated with
      various pathologies which cause pain in the posterior branches of the lumbar
      spinal nerves due to entrapment, mechanical irritation or inflammatory reaction
      and/or degeneration. The posterior branches are of significant functional
      importance, which is related to the function of the structures they supply,
      including facet joints, which are the basic biomechanical units of the spine. Low
      back pain caused by facet joint pathology may be triggered e.g. by simple
      activities, such as body rotations, unnatural positions, lifting heavy weights or
      excessive bending as well as chronic overloading with spinal hyperextension. Pain
      usually presents at the level of the lumbosacral junction (L 5 -S 1 ) and in the
      lower lumbar spine (L 4-5 , L 3-4 ). In the absence of specific diagnostic
      criteria, it is only possible to conclude that patients display tenderness at the
      level of the affected facet joint and that the pain is triggered by extension.
      Differential diagnosis for low back pain is difficult, since the pain may
      originate from various structures. The most reliable method of identifying Lumbar
      Facet Syndrome has been found to be a positive response to an analgesic procedure
      in the form of a block of the medial branch or intraarticular injection. There
      appear to be good grounds for conducting further studies and developing
      unequivocal diagnostic tests.

PMID- 28508762
TI  - Results of the Treatment of Infected Nonunions of the Lower Limbs Using the
      Ilizarov Method.
AB  - BACKGROUND: Infected nonunion is a complex complication of the treatment of long
      bone fractures. An in creased incidence of injuries, including high energy
      injuries (often open ones), contributes to a higher incidence of nonunion. These
      primarily infected injuries cause osteomyelitis, which prevents bone union,
      resulting in an infected nonunion. The Ilizarov method meets the biological and
      biomechanical treatment requirements, opti mising the process of inflammation
      healing and producing bone union. MATERIAL AND METHODS: A total of 54 patients
      were treated in 2000-2014 for nonunion in the lower limbs with the Ilizarov
      method, which was used after previous treatment had failed. The subjects
      underwent intra operative resection of the locus of infection, sequestrectomy and
      a Judet procedure, followed by the use of the Ilizarov apparatus and bone
      transport, depending on the defect. RESULTS: Inflammation healed in 52 patients
      (96%) and bone union was achieved in 46 patients (86%). Good outcomes with healed
      inflammation and bone union were reported in 76% of the cases, fair outcomes with
      tem porary elimination of the inflammation and without bone union in 16%, and
      poor outcomes without inflam ma tion healing and without bone union in 7%.
      CONCLUSIONS: Treatment of infected nonunion can only be effective after
      eliminating endogenous inflamma tory foci, covering skin defects, ensuring a good
      condition of the skin and soft tissues, restoring normal blood supply to the bone
      fragments, and good biomechanical fixation of the fragments with dynamisation or
      compression. The Ilizarov method is a method of choice in the treatment of cases
      of infected nonunion where other treatments have failed.

PMID- 28508763
TI  - Radiological Outcomes of Overhead Traction Therapy for Developmental Dysplasia of
      the Hip in Non-ambulatory Children.
AB  - BACKGROUND: Infants with a dislocated and unstable hip that does not lend itself
      to stabilisation may be treated using overhead traction to achieve gradual
      reduction of the hip joint. The aim of this paper was to analyse the radiological
      outcomes of overhead traction therapy and the effect of duration of traction on
      the occurrence of complications and final treatment outcomes. Material and
      methodd. A retrospective analysis of medical records of 26 children (34 affected
      hips) involved three independent observers assessing radiological parameters
      before the surgery and at follow-up visits at least two years after the therapy.
      RESULTS: Overhead traction was used for an average of 35 days (range: 15-43
      days). Twenty six hips were treated solely with reduction and immobilisation in a
      'human position' plaster cast. Three hips were qualified for surgery immediately
      after a preliminary traction period. Five hips showed a suboptimal result
      following the immobilisation period. A MANOVA model revealed that the following
      factors had a significant effect on the treatment outcome: superior centring
      ratio of Smith (with the lowest values recorded in patients with residual hip
      dysplasia, p = 0.001) and acetabular angle of Sharp (with the lowest values found
      in patients requiring surgery, p = 0.01). Statistical tests did not show a
      correlation between the duration of traction and disturbance of proximal femoral
      metaphysis growth assessed according to Bucholz and Ogden classification. Fifteen
      hips were classified as type I, eight hips were graded as type II and also eight
      hips as type III. CONCLUSIONS: The lowest values of acetabular angle of Sharp
      were recorded in patients requiring surgery and the lowest superior centring
      ratio of Smith was found in those with residual hip dysplasia. The duration of
      overhead traction did not directly correlate with the final outcome; it only
      seemed to be an indicator of the severity of hip dysplasia. Routine use of
      overhead traction before undertaking closed reduction does not probably decrease
      the incidence of proximal femoral growth disturbance.

PMID- 28508764
TI  - Current Incidence of Different Morphological Types of Malignant Metastases to the
      Spine Based on Magnetic Resonance Imaging.
AB  - BACKGROUND: Malignant tumours particularly often metastasise to the spine,
      causing considerable pain and limiting the patient's physical function. Standard
      therapy consists in surgical treatment with adjuvant radiotherapy. The
      qualification for surgery is a multifaceted process and detailed analysis of the
      morphology of the metastasis is a key factor. Numerous types of classification of
      metastatic lesions exist, among which the Tomita system, based on MRI findings,
      appears to be the most practical. The aim of this paper is to present the current
      incidence of different morphological types of metastases as classified by the
      Tomita system. MATERIALS AND METHODS: This work was based on cases treated at the
      Department of Oncological Orthopaedics of the Specialist Hospital in Brzozow -
      Podkarpacie Oncological Centre from 2010-2015. A total of 854 patients with
      spinal metastases were hospitalised at the department. All patients underwent a
      CT and MRI of the spine and their metastatic lesions were classified as one of
      the 7 types described by Tomita. The incidence of different morphological types
      of metastases per type of the primary tumour was also determined. RESULTS: Most
      patients treated at the department had advanced disease as a result of diagnostic
      delays. Types T3-T7 were found in 91% of the patients and T7 in 44%. The highest
      incidence of advanced disease was seen among patients with breast cancer and
      myeloma. Higher pain severity and incidence of neurological complications were
      noted in patients with multisite lesions. Neurological deficits were diagnosed in
      228 patients, of whom 68% were classified as Type T6 or T7. Most of the T6/T7
      patients were unable to walk unassisted and required constant help from their
      family or medical staff. CONCLUSIONS: The Tomita system allows for easy and clear
      classification of the morphology of malignant metastases. 66% of patients treated
      at our department had multisite T6 or T7 metastases.

PMID- 28508765
TI  - A Comparison of Outcomes of Treatment with Resection Prosthesis of the Hip in
      Revision and Oncological Surgery.
AB  - INTRODUCTION: The introduction of resection prostheses paved the way for the
      development of limb-sparing surgery in patients with primary or metastatic bone
      tumours. After some time, the developing possibilities of treatment of extensive
      bone defects allowed for the use of resection prostheses as an emergency
      procedure in patients undergoing revision surgery due to hip implant loosening.
      The aim of this paper is to compare treatment outcomes in patients receiving the
      Modular Universal Tumour and Revision System (MUTARS) resection prosthesis during
      arthroplasty performed for different indications: treatment of a tumour
      metastasis and revision surgery in cases of implant loosening. MATERIAL AND
      METHODS: A total of 34 MUTARS femoral resection prostheses were implanted in 34
      patients at the Cracow Centre of Rehabilitation and Orthopaedics between December
      2008 and January 2016. The procedure was indicated due to the presence of a
      tumour metastasis (in 13 cases) or due to implant loosening that required
      revision arthroplasty with a resection prosthesis (in 21 cases). Femoral bone
      defects were classified according to Paprosky and Katthagen in all operated
      patients. Clinical assessment was conducted with the modified Harris Hip Score
      before the surgery and at one year after the procedure. In addition, pain
      intensity was assessed with a Visual Analogue Scale (VAS). RESULTS: No
      statistically significant differences were observed between the groups with
      respect to the length of the femoral bone resected, perioperative blood loss and
      the number of packed red blood cell (PRBC) units required. A statistically
      significant difference was found in duration of the surgery and hospital stay,
      which were longer in the revision arthroplasty group. No statistically
      significant differences were observed between the groups in the post-operative
      HHS scores and pain assessment in the VAS scale. The revision arthroplasty group
      showed significantly more dislocations (8 vs. 2) and cases of surgical site
      infection. CONCLUSIONS: 1.The use of the MUTARS modular resection prosthesis
      allows for fast clinical improvement that meets the patient's expectations both
      in oncological treatment and in revision arthroplasty. 2. The extent of bone
      resection, procedure duration and perioperative blood loss associated with the
      surgical placement of a resection prosthesis are similar in oncological treatment
      and in revision arthroplasty. 3. The use of a resection prosthesis in revision
      arthroplasty is associated with a high risk of implant dislocation.

PMID- 28508766
TI  - Comparison of Quality of Life of Patients after Hip Disarticulation and Those
      after Stump Lengthening with Modular Prosthesis.
AB  - BACKGROUND: Disarticulation has been used less and less often in the treatment of
      musculoskeletal neoplasms; however, in some cases it allows the patient to
      achieve good oncological and functional outcomes. The aim of this paper is to
      present the possibilities, surgical technique and treatment outcomes of patients
      after hip disarticulation and stump lengthening with a modular prosthesis.
      MATERIAL AND METHODS: Three classic hip disarticulation surgeries and 2 hip
      disarticulation procedures with stump lengthening with a modular prosthesis were
      performed at the Department of Oncological Orthopaedics in Brzozow in 2013 and
      2014. The present paper discusses the indications, surgical technique and
      outcomes. Pain intensity was assessed in a VAS scale and physical function was
      measured with the Karnofsky scale. The mental status of the patients was analysed
      in the Beck Depression Inventory and the ability to perform daily living
      activities was evaluated according to Katz. The ability to walk after surgery was
      assessed. RESULTS: Patients after hip disarticulation showed considerably worse
      functional outcomes. The mean physical function score was 53 points in the
      Karnofsky scale and 3.33 points in the Katz scale. The patients had difficulty
      walking and did not ambulate with their prostheses. They reported problems with
      sitting and using the toilet. Patients with lengthened stumps showed visibly
      better physical function scores, achieving, on average, 65 points in the
      Karnofsky scale and 5.5 points in the Katz scale. These patients used their
      prostheses, ambulated efficiently and were independent. CONCLUSIONS: Stump
      lengthening with a modular prosthesis in patients after hip disarticulation
      results in significantly better outcomes than the classic procedure.

PMID- 28508767
TI  - Biopsychosocial Rehabilitation Programme for Patients with Chronic Back Pain.
      Pilot Study.
AB  - BACKGROUND: In the search for effective and comprehensive therapies of back pain,
      an increasing emphasis in being placed on the biopsychosocial model and
      multidimensional support programmes for patients as well the use of modern
      technologies in this area of medicine. This study aimed to assess a programme of
      customised ad hoc physiotherapeutic consultations for patients with back pain who
      had been on the waiting list for rehabilitation treatment for a long time.
      MATERIAL AND METHOD: The study group comprised 68 patients of the Rehabilitation
      Centre Non-Public Health Care Institution who had been waiting for rehabilitation
      treatment for at least three months. The patients, diagnosed with chronic back
      pain and aged 40-80 years, were randomly assigned into two groups. The
      experimental group took part in a programme of three consultations, provided on
      average once a month. The patients from both groups were assessed after the three
      month programme, immediately before the commencement of the prescribed
      rehabilitation treatment. We evaluated the pain threshold at trigger points of
      selected muscles using the algometric method (kg/cm 2 ), subjective assessment of
      pain (VAS), functional limitations (Rolland Morris Disability Questionnaire) and
      quality of life (36-Item Short Form Health Survey, SF-36). The statistical
      analysis of the results used non-parametric methods: significance of differences
      between the groups was evaluated with the Mann-Whitney U test and correlations
      between the variables were assessed separately for each group using Spearman's
      rank order correlation. The significance threshold was accepted at alpha=0.05.
      RESULTS: The algometric evaluation of all the muscles revealed significantly
      lower sensitivity to pain, demonstrated by a higher pain threshold (p<0.0001), in
      the experimental group. Moreover, this group also included a much smaller
      percentage of patients with a high level of functional limitations according to
      the Rolland Morris Disability Questionnaire. The quality of life evaluation
      revealed that the control group scored poorer in the mental domain (p=0.02).
      CONCLUSIONS: The ad hoc intervention programme for patients referred for
      rehabilitation due to chronic back pain showed demonstrable beneficial effects
      with regard to their psychophysical health. Similar programmes should be more
      readily offered to patients at health care centres and implemented into clinical
      practice.

PMID- 28508768
TI  - Inveterate (42-year-old) Hip Dislocation Treated with Arthroplasty. A Case Study.
AB  - Dislocation of the hip usually results from a high-energy injury sustained during
      a road accident. Inveterate dislocations persisting for many months or years are
      extremely rare. Selection of an appropriate treatment method is not easy and is
      always associated with the risk of serious complications. The present authors
      hope that a description of the course of diagnostic work-up and treatment of a
      patient in whom a hip dislocation persisted for 42 years will prove interesting
      and helpful for orthopaedists who may encounter such a case in their practice.
      The patient sustained a dislocation of the right hip in 1974. He did not agree to
      undergo reduction immediately after the injury. Initially, he experienced
      extremely severe pain and difficulty walking, but gradually learned to walk
      without crutches and even took up a job. The limb was considerably shortened with
      only minimal movement in the hip joint. The pelvic geometry was altered and
      spinal scoliosis developed. In the last several years, the patient experienced a
      significant increase in pain and a decrease in function that prevented him from
      walking unassisted. Following a thorough physical examination, and based on
      computed tomography images, the patient was qualified for hip arthroplasty. An
      analysis of the available literature prompted the present authors to use a
      cemented implant and not to use bone grafts. Early treatment outcomes are good.

PMID- 28508769
TI  - Diagnostic Difficulties in Bone Sarcoidosis Imaging. A Cases Study.
AB  - Sarcoidosis is a multiorgan inflammatory disease that rarely involves the
      musculoskeletal system. A typical radiographic presentation is only noted with
      phalangeal lesions in the hands and feet, and other skeletal sites of sarcoidosis
      are a diagnostic imaging challenge [1]. We describe two cases of patients with
      sarcoidosis in whom pathologic bone marrow lesions were diagnosed on MRI scans.
      The magnetic resonance findings were non-specific and metastatic lesions or
      multiple myeloma were suspected. The case analysis serves to point to limitations
      of imaging studies in diagnosing bone sarcoidosis and underline the importance of
      cooperation between the radiologist and the clinician. The role of magnetic
      resonance imaging in the diagnostic algorithm for bone sarcoidosis should mostly
      focus on locating lesions, indicating biopsy sites and follow-up of
      abnormalities.

PMID- 28508770
TI  - Romuald Weglowski (1876-1935) - Orthopaedic Surgeon, Forgotten Pioneer of Limb
      Saving Tumour Surgery.
AB  - On May 16, 1914, The Lancet Journal published a paper by Romuald Weglowski, a
      Polish-born professor of Moscow University, entitled "Malignant tumours of bones:
      a new method in conservative operative treatment." The idea of biological
      resection presented in the paper consisted in thermocoagulation of the apparently
      cancerous part of a bone with a jet of steam. According to the author, dead bone
      rid of live malignant cells reconstructed itself quickly, which helped to
      preserve the functionality of the organ without considerable limitations. The
      events of the First World War, political changes in tsarist Russia and the
      recovery of independence by Poland greatly complicated Weglowski's professional
      career. We thought it would be interesting to present the life story of the great
      Polish surgeon in the context of his own method of bone cancer treatment, which
      without doubt marked the beginning of Polish orthopaedic oncology aimed at limb
      saving surgery.

PMID- 28508771
TI  - Alkylthiol self-assembled monolayers on Au(111) with tailored tail groups for
      attaching gold nanoparticles.
AB  - Self-assembled monolayers (SAMs) on Au(111) are able to control the functionality
      of a gold surface. We use scanning tunnelling microscopy (STM) in air and contact
      angle measurements to compare the morphology and the chemistry of three
      alkylthiol SAMs differing by their tail groups: 1,9-nonanedithiol (NDT), 1,4
      butanedithiol (BDT) and 11-mercaptoundecanol (MUOH). STM reveals very different
      morphologies: a hexagonal lattice for MUOH and parallel rows for NDT and BDT. In
      the case of NDT, we find that the thiol tail groups may form disulfide bridges
      with long immersion times. The availability of the -SH group for chemical
      reactions is demonstrated by attaching gold nanoparticles (AuNPs). When the thiol
      tail group is available, AuNPs readily attach as shown with atomic force
      microscopy (AFM). When disulfide bridges are formed, the gold surface is not able
      to bind nanoparticles.

PMID- 28508772
TI  - Concept-Based Retrieval from Critical Incident Reports.
AB  - BACKGROUND: Critical incident reporting systems (CIRS) are used as a means to
      collect anonymously entered information of incidents that occurred for example in
      a hospital. Analyzing this information helps to identify among others problems in
      the workflow, in the infrastructure or in processes. OBJECTIVES: The entire
      potential of these sources of experiential knowledge remains often unconsidered
      since retrieval of relevant reports and their analysis is difficult and time
      consuming, and the reporting systems often do not provide support for these
      tasks. The objective of this work is to develop a method for retrieving reports
      from the CIRS related to a specific user query. METHODS: atural language
      processing (NLP) and information retrieval (IR) methods are exploited for
      realizing the retrieval. We compare standard retrieval methods that rely upon
      frequency of words with an approach that includes a semantic mapping of natural
      language to concepts of a medical ontology. RESULTS: By an evaluation, we
      demonstrate the feasibility of semantic document enrichment to improve recall in
      incident reporting retrieval. It is shown that a combination of standard keyword
      based retrieval with semantic search results in highly satisfactory recall
      values. CONCLUSION: In future work, the evaluation should be repeated on a larger
      data set and real-time user evaluation need to be performed to assess user
      satisfactory with the system and results.

PMID- 28508773
TI  - Word Sense Disambiguation of Medical Terms via Recurrent Convolutional Neural
      Networks.
AB  - BACKGROUND: Tagging text data with codes representing biomedical concepts plays
      an important role in medical data management and analysis. A problem occurs if
      there are ambiguous words linked to several concepts. OBJECTIVES AND METHODS:
      This study aims at investigating word sense disambiguation based on word
      embedding and recurrent convolutional neural networks. The study focuses on terms
      mapped to multiple concepts of the Unified Medical Language System (UMLS).
      RESULTS: We created 20 text processing pipelines trained on a subset of the MeSH
      Word Sense Disambiguation (MSH WSD) data set, each pipeline disambiguating the
      sense of one word. The pipelines were then tested on a disjoint subset of MSH WSD
      data. Most pipelines achieved good or even excellent results (70% of the
      pipelines achieved at least 90% accuracy, 40% achieved at least 98% accuracy).
      One poor-performing outlier was detected. CONCLUSION: The proposed approach can
      serve as a basis for an up-scaled system combining pipelines for many ambiguous
      words. The methods used here recently proved very successful in other fields of
      text understanding and can be expected to scale-up with improved availability of
      training data.

PMID- 28508774
TI  - Arden Syntax MLM Building Blocks for Microbiological Concepts and Their
      Application in Infection Surveillance.
AB  - BACKGROUND: The diagnosis - and hence definitions - of healthcare-associated
      infections (HAIs) rely on microbiological laboratory test results in specific
      constellations. OBJECTIVES: To construct a library that provides interoperable
      building blocks for the analysis of microbiological laboratory test results.
      METHODS: We used Java for preprocessing raw microbiological laboratory test
      results and Arden Syntax for knowledge-based querying of data based on
      microbiology information elements used in European surveillance criteria for
      HAIs. To test the library and quantify how often these information elements occur
      in the data, we performed a retrospective cohort study on adult patients admitted
      for at least 24 hours to an intensive care unit at the Vienna General Hospital in
      2013. RESULTS: We identified eleven information elements for which information
      was electronically available. These elements were identified positively 1,239
      times in 1,184 positive microbiology tests from 563 patients. DISCUSSION: The
      availability of a library for the analysis of microbiology laboratory test
      results in HAI terms facilitates electronic HAI surveillance.

PMID- 28508775
TI  - Semantic Technologies for Re-Use of Clinical Routine Data.
AB  - Routine patient data in electronic patient records are only partly structured,
      and an even smaller segment is coded, mainly for administrative purposes. Large
      parts are only available as free text. Transforming this content into a
      structured and semantically explicit form is a prerequisite for querying and
      information extraction. The core of the system architecture presented in this
      paper is based on SAP HANA in-memory database technology using the SAP Connected
      Health platform for data integration as well as for clinical data warehousing. A
      natural language processing pipeline analyses unstructured content and maps it to
      a standardized vocabulary within a well-defined information model. The resulting
      semantically standardized patient profiles are used for a broad range of clinical
      and research application scenarios.

PMID- 28508776
TI  - Development and Validation of a Multivariable Prediction Model for the Occurrence
      of Delirium in Hospitalized Gerontopsychiatry and Internal Medicine Patients.
AB  - Delirium is an acute confusion condition, which is common in elderly and often
      misdiagnosed in hospitalized patients. Early identification and prevention of
      delirium could reduce morbidity and mortality rates in those affected and reduce
      hospitalization costs. We have developed and validated a multivariate prediction
      model that predicts delirium and gives an early warning to physicians. A large
      set of patient electronic medical records have been used in developing the
      models. Classical learning algorithms have been used to develop the models and
      compared the results. Excellent results were obtained with the feature set and
      parameter settings attaining accuracy of 84%.

PMID- 28508777
TI  - How to Link SNOMED CT Procedure and WHO International Classification of Health
      Interventions (ICHI).
AB  - Among different used healthcare terminology resources there is a need to link
      them to ease their interoperability. SNOMED CT is the most detailed clinical
      reference terminology for procedure used in the Electronic Health Record (EHR).
      WHO developed since 2006 an aggregated classification named ICHI required for
      statistics and resource allocation. It is based on an ontology framework defined
      in ISO 1828 named Categorial Structure (CAST) for surgical procedures. We present
      ICHI coding structure, ISO 1828 CAST standard for surgical procedures and SNOMED
      CT procedures hierarchy concept model and their relations. We demonstrate the
      obstacles to align ICHI coding structure with ISO 1828 CAST which can be linked
      with SNOMED CT procedures hierarchy concept model. We recommend to update ICHI
      coding structure to decrease the gap with ISO 1828 CAST and SNOMED CT concept
      model for procedures hierarchy to allow users to share the different terminology
      resources.

PMID- 28508778
TI  - Supporting Molecular Tumor Boards in Molecular-Guided Decision-Making - The
      Current Status of Five German University Hospitals.
AB  - BACKGROUND: German university hospitals have started to establish molecular tumor
      boards in order to enable physicians to make molecular-guided decisions.
      OBJECTIVE: Our aim was to describe the organizational structure and procedures
      which are currently supporting the molecular tumor boards of five German
      university hospitals. METHODS: We conducted semi-structured interviews with
      experts of five university hospitals between December 2016 and February 2017.
      RESULTS: We observed heterogeneity in both the organization of genetic testing
      and the management of the molecular tumor boards among the five hospitals. They
      used free-text documents in most of their support procedures rather than machine
      readable documents. CONCLUSION: There are three potentialities to support the
      process from genetic testing to reporting within the molecular tumor boards: (i)
      standardized pipeline to integrate automated variant calling and annotation; (ii)
      tools supporting the experts in creating their reports and presentations and
      (iii) implementing pharmacogenomic CDSS into clinical routine.

PMID- 28508779
TI  - Ad hoc Participation in Professional Tele-Collaboration Platforms.
AB  - Tele-collaboration between medical professionals is well established for
      specialties like radiology, cardiology or pathology. Typically these applications
      do not allow for ad hoc participation of non-registered users like patients and /
      or medical professionals. This paper describes an approach for extending these
      tele-applications to non-registered users and providing ad hoc participation with
      means for providing and accessing data. A light weight, web-based approach is
      used to assure acceptance and ease of use while maintaining and complying to the
      required regulations regarding authentication, authorization and protection of
      personal data. The approach has been implemented and is in use with a nationwide
      tele-collaboration network in Germany.

PMID- 28508780
TI  - Challenges and Approaches to Make Multidisciplinary Team Meetings Interoperable -
      The KIMBo Project.
AB  - BACKGROUND: Multidisciplinary team meetings (MDTMs) are already in use for
      certain areas in healthcare (e.g. treatment of cancer). Due to the lack of common
      standards and accessibility for the applied IT systems, their potential is not
      yet completely exploited. OBJECTIVES: Common requirements for MDTMs shall be
      identified and aggregated into a process definition to be automated by an
      application architecture utilizing modern standards in electronic healthcare,
      e.g. HL7 FHIR. METHODS: To identify requirements, an extensive literature review
      as well as semi-structured expert interviews were conducted. RESULTS: Results
      showed, that interoperability and flexibility in terms of the process are key
      requirements to be addressed. An architecture blueprint as well as an aggregated
      process definition were derived from the insights gained. To evaluate the
      feasibility of identified requirements, methods of explorative prototyping in
      software engineering were used. CONCLUSION: MDTMs will become an important part
      of modern and future healthcare but the need for standardization in terms of
      interoperability is imminent.

PMID- 28508781
TI  - Two Years of tranSMART in a University Hospital for Translational Research and
      Education.
AB  - BACKGROUND: For translational research, software platforms such as tranSMART with
      an integrated view of both clinical and omics data have gained more and more
      attention in the last years. OBJECTIVES: We wanted to examine the success and
      failures of tranSMART in the fields of translational research and education by
      looking at the examples of six use cases at our hospital. We wanted to point out
      suitable scenarios and user groups as well as still existing challenges and
      limitations. METHODS: We sum up the experience we made with our use cases with a
      focus on lessons learned. RESULTS: tranSMART was successfully established by a
      bottom-up approach at our university hospital and has been running for more than
      two years now. It has been used in four translational research projects as well
      as in education in the context of lectures and bachelor/master theses.
      CONCLUSION: tranSMART can be a very useful tool for translational research and
      education. But it should be used with both care and statistical knowledge to
      avoid wrong conclusions. Some technical constraints, especially for data
      modeling, still limit many applications. Version control and data provenance are
      remaining challenges.

PMID- 28508782
TI  - The Use of RESTful Web Services in Medical Informatics and Clinical Research and
      Its Implementation in Europe.
AB  - BACKGROUND: RESTful web services nowadays are state-of-the-art in business
      transactions over the internet. They are however not very much used in medical
      informatics and in clinical research, especially not in Europe. OBJECTIVES: To
      make an inventory of RESTful web services that can be used in medical informatics
      and clinical research, including those that can help in patient empowerment in
      the DACH region and in Europe, and to develop some new RESTful web services for
      use in clinical research and regulatory review. METHODS: A literature search on
      available RESTful web services has been performed and new RESTful web services
      have been developed on an application server using the Java language. RESULTS:
      Most of the web services found originate from institutes and organizations in the
      USA, whereas no similar web services could be found that are made available by
      European organizations. New RESTful web services have been developed for LOINC
      codes lookup, for UCUM conversions and for use with CDISC Standards. DISCUSSION:
      A comparison is made between "top down" and "bottom up" web services, the latter
      meant to answer concrete questions immediately. The lack of RESTful web services
      made available by European organizations in healthcare and medical informatics is
      striking. CONCLUSION: RESTful web services may in short future play a major role
      in medical informatics, and when localized for the German language and other
      European languages, can help to considerably facilitate patient empowerment. This
      however requires an EU equivalent of the US National Library of Medicine.

PMID- 28508783
TI  - Automatic Conversion of Metadata from the Study of Health in Pomerania to ODM.
AB  - BACKGROUND: Electronic collection and high quality analysis of medical data is
      expected to have a big potential to improve patient care and medical research.
      However, the integration of data from different stake holders is posing a crucial
      problem. The exchange and reuse of medical data models as well as annotations
      with unique semantic identifiers were proposed as a solution. OBJECTIVES: Convert
      metadata from the Study of Health in Pomerania to the standardized CDISC ODM
      format. METHODS: The structure of the two data formats is analyzed and a mapping
      is suggested and implemented. RESULTS: The metadata from the Study of Health in
      Pomerania was successfully converted to ODM. All relevant information was
      included in the resulting forms. Three sample forms were evaluated in-depth,
      which demonstrates the feasibility of this conversion. CONCLUSION: Hundreds of
      data entry forms with more than 15.000 items can be converted into a standardized
      format with some limitations, e.g. regarding logical constraints. This enables
      the integration of the Study of Health in Pomerania metadata into various
      systems, facilitating the implementation and reuse in different study sites.

PMID- 28508784
TI  - VR Medical Gamification for Training and Education.
AB  - The new virtual reality based medical applications is providing a better
      understanding of healthcare related subjects for both medical students and
      physicians. The work presented in this paper underlines gamification as a concept
      and uses VR as a new modality to study the human skeleton. The team proposes a
      mobile Android platform application based on Unity 5.4 editor and Google VR SDK.
      The results confirmed that the approach provides a more intuitive user experience
      during the learning process, concluding that the gamification of classical
      medical software provides an increased interactivity level for medical students
      during the study of the human skeleton.

PMID- 28508785
TI  - Assessing the Educational Needs of Health Information Management Staff of the
      Mashhad University of Medical Sciences, Iran.
AB  - Health information management (HIM) professionals have a combination of skills
      and, at the same time, the demand for their skills in the health system is
      increasing rapidly. This study aimed to assess the educational needs of the HIM
      staff in Iran. This descriptive analytical study was conducted in eight teaching
      hospitals. It was found that the maximum educational needs concerned the
      knowledge of medical terminology, occupational safety, legal aspects, the newest
      rules and regulations, and ministry guidelines, while the least of the felt needs
      related to insurance and other aspects of registry, data ownership, and data
      quality. The need to learn about coding and classifications had a significant
      relationship with work experience (P = 0.045) and those with a work experience of
      6 to 10 years had fewer needs. Educational needs were also significantly
      associated with the number of years since graduation (P = 0.005), as those with 5
      10 years' experience after post-graduation had lesser needs than others. Those
      who plan educational programs for health information professionals must have a
      comprehensive view of the needs of the health system. Participation of
      specialists of different fields must be considered in educational planning of
      such interdisciplinary fields.

PMID- 28508786
TI  - Implementation of Nationwide Electronic Health Record in Albania: A Case Study.
AB  - BACKGROUND: This paper presents a case study of the nationwide implementation of
      an Electronic Health Record system based on industry standards. OBJECTIVES: To
      critically review the finalized nationwide EHR implementation in Albania,
      pointing out the achievements and the shortcomings, gained knowledge and sharing
      lessons learned. METHODS: This paper reports on our analysis of the project's
      documentation, first-hand experience working with healthcare professionals during
      and after project implementation. The initial system uptake analysis has been
      made using EHR usage statistics. RESULTS: Despite very poor initial ICT
      infrastructure, minimal or non-existing medical nomenclature and a rather
      challenging project schedule, the nationwide implementation of the EHR system was
      successfully completed in less than two years. CONCLUSION: Although the system is
      already in use by 79 healthcare providers and is covering secondary and tertiary
      care, the majority of clinical data still remains in paper format; the access for
      clinicians to the system is limited due to insufficient ICT infrastructure.

PMID- 28508787
TI  - The Importance of Gene-Drug-Drug-Interactions in Pharmacogenomics Decision
      Support: An Analysis Based on Austrian Claims Data.
AB  - While pharmacogenomic testing combined with clinical decision support has the
      potential to increase the safety and efficacy of medical treatments, the intake
      of multiple prescription drugs can - if not sufficiently addressed by decision
      support solutions - impair the effectiveness of such interventions by modulating
      the capacity of precisely those enzymes whose function pharmacogenomic tests try
      to predict. We quantified the potential extent of such drug-mediated mismatches
      between genotype-derived phenotypes and real phenotypes, commonly called
      "phenoconversion", by screening claims data from 1,587,829 Austrian health
      insurance holders of the years 2006 and 2007 for concomitant prescriptions of
      drugs that can be dosed based on pharmacogenomics, and drugs that modulate enzyme
      activity. In total, 232,398 such prescription overlaps were detected, of which
      more than half (54.6%) could be attributed to co-prescriptions of moderate or
      strong modulators. Our results indicate that prescription drug-mediated
      phenoconversion is not uncommon, and should therefore be adequately reflected in
      decision support solutions by integrating algorithms to detect potential gene
      drug-drug interactions.

PMID- 28508788
TI  - KALIS - An eHealth System for Biomedical Risk Analysis of Drugs.
AB  - BACKGROUND: In Germany, adverse drug reactions and events cause hospitalizations,
      which lead to numerous thousands of deaths and several million Euros in
      additional health costs annually. OBJECTIVES: Approximately one in two deaths
      could be avoided by an appropriate system for risk analysis of drugs. METHODS:
      The integration and storage of several data sources from life sciences are an
      ongoing need to address various questions with respect to drug therapy. A
      software architecture for data integration was implemented in order to build up a
      new data warehouse named KALIS-DWH, which includes pharmacological, biomolecular
      and patient-related data. RESULTS: Based on this comprehensive KALIS-DWH, an
      eHealth system named KALIS for biomedical risk analysis of drugs was implemented.
      The task-specific modules of KALIS offer efficient algorithms for analyzing
      medication and supporting decision-making in drug therapy. CONCLUSION: KALIS is
      meant to be a web-based information system for health professionals and
      researchers. KALIS provides comprehensive knowledge and modules for risk analysis
      of drugs, which can contribute to minimizing prescribing errors.

PMID- 28508789
TI  - Propose of Standards Based IT Architecture to Enrich the Value of Allergy Data by
      Telemonitoring Data.
AB  - Interoperability is a key requirement for any IT-System to be future proof and
      cost efficient, due to the increasing interaction of IT-Systems in Healthcare.
      This feasibility study is part of a larger project focusing on the
      conceptualization and evaluation of interoperable and modular IT-Framework
      components for exchanging big data information sets. Hence, this project
      investigates the applicability of a standard based IT-Architecture for the
      integration of Personal Health Devices data and open data sources. As a proof of
      concept use case, pollen forecast data from the Medical University of Vienna were
      combined with Personal Health Device data and a data correlation was
      investigated. The standards were identified as well as selected in expert's
      reviewed and the Architecture was designed based on a literature research.
      Subsequently the prototype was implemented and successfully tested in
      interoperability tests. The study shows that the architecture meets the
      requirements. It can be flexibly extended according to further requirements due
      to its generic setup. However, further extensions of the Interoperability
      Connector and a full test setup needs to be realized in future.

PMID- 28508790
TI  - Development of a Multidisciplinary and Telemedicine Focused System Database.
AB  - BACKGROUND: Tele-rehabilitation at home is one of the promising approaches in
      increasing rehabilitative success and simultaneously decreasing the financial
      burden on the healthcare system. OBJECTIVES: Novel and mostly mobile devices are
      already in use, but shall be used in the future to a higher extent for allowing
      at home rehabilitation processes at a high quality level. The combination of
      exercises, assessments and available equipment is the basic objective of the
      presented database. METHODS: The database has been structured in order to allow
      easy-to-use and fast access for the three main user groups. Therapists - looking
      for exercise and equipment combinations - patients - rechecking their tasks for
      home exercises - and manufacturers - entering their equipment for specific use
      cases. RESULTS: The database has been evaluated by a proof of concept study and
      shows a high degree of applicability for the field of rehabilitative medicine.
      Currently it contains 110 exercises/assessments and 111 equipment/systems.
      CONCLUSION: Foundations of presented database are already established in the
      rehabilitative field of application, but can and will be enhanced in its
      functionality to be usable for a higher variety of medical fields and
      specifications.

PMID- 28508791
TI  - Rehabilitation Risk Management: Enabling Data Analytics with Quantified Self and
      Smart Home Data.
AB  - A variety of acute and chronic diseases require rehabilitation at home after
      treatment. Outpatient rehabilitation is crucial for the quality of the medical
      outcome but is mainly performed without medical supervision. Non-Compliance can
      lead to severe health risks and readmission to the hospital. While the patient is
      closely monitored in the hospital, methods and technologies to identify risks at
      home have to be developed. We analyze state-of-the-art monitoring systems and
      technologies and show possibilities to transfer these technologies into
      rehabilitation monitoring. For this purpose, we analyze sensor technology from
      the field of Quantified Self and Smart Homes. The available sensor data from this
      consumer grade technology is summarized to give an overview of the possibilities
      for medical data analytics. Subsequently, we show a conceptual roadmap to
      transfer data analytics methods to sensor based rehabilitation risk management.

PMID- 28508792
TI  - Identification of Cost Indicators with Significant Economic Impact on the Total
      Treatment Costs of Chronic Heart Failure Patients - A Meta-Analysis.
AB  - : Increasing treatment costs of HF patients affect the initiation of appropriate
      treatment method. Divergent approaches to measure the costs of treatment and the
      lack of common cost indicators impede the comparison of therapy settings.
      OBJECTIVES: In the context of the present meta-analysis, key cost indicators from
      the perspective of healthcare providers are to be identified, described, analyzed
      and quantified. This review helps narrowing down the cost indicators, which have
      the most significant economic impact on the total treatment costs of HF patients.
      Telemedical services are to be compared to standard therapy methods. METHODS: The
      identification process was based on several steps. For the quantitative
      synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement. An additional set of criteria was defined for the
      following qualitative analysis. RESULTS: 5 key cost indicators were identified
      with significant economic impact on the treatment costs of HF patients.
      CONCLUSION: 95% of the reported treatment costs could be captured based on the
      identified cost indicators.

PMID- 28508793
TI  - POSEIDON - Bringing Assistive Technology to People with Down Syndrome: Results of
      a Three Year European Project.
AB  - The POSEIDON project aimed to increase the independence and autonomy of people
      with Down syndrome with the help of technical assistants. It followed a user
      centered approach by involving people with Down syndrome and their parents,
      carers etc. A requirement analysis was the first step of the project. It became
      clear that people with Down syndrome especially need support in the areas of time
      management, mobility and money handling. Different applications were developed
      which were tested and evaluated in two field tests in three countries. Results
      indicate that POSEIDON can help to overcome daily challenges and that it can
      increase the autonomy and independence of people with Down syndrome.

PMID- 28508794
TI  - On the Prototyping of an ICT-Enhanced Toilet System for Assisting Older Persons
      Living Independently and Safely at Home.
AB  - Standard toilets often do not meet the needs of a significant number of older
      persons and persons with disabilities. The EU funded iToilet project aims at
      design and development of a new type of ICT enhanced modular toilet system which
      shall be able to support autonomy, dignity and safety of older persons living at
      home. Methodologically the project started with gathering user requirements by
      means of questionnaires, interviews and focus group discussion involving a total
      of 74 persons, thereof 41 subjects with movement disorders (primary users), 21
      caregivers (secondary users) and 12 healthcare managers (tertiary users). Most
      important wishes were bilateral removable handrails, height and tilt adjustment,
      emergency detection, simplicity. In parallel to the ongoing technical development
      participatory design activities have been carried out at user test sites in order
      to continuously involve users into the design process and to allow quick feedback
      with regards to early prototype parts. The project currently is working on the
      finalization of the first prototype ready to enter the lab trial stage in spring
      2017. The experiences will be used for redesigning a prototype 2 which is planned
      to be tested in real life settings early 2018.

PMID- 28508795
TI  - Assistive Solutions in Practice: Experiences from AAL Pilot Regions in Austria.
AB  - Since 2012 six AAL pilot regions were launched in Austria. The main goal of these
      pilot regions is to evaluate the impact of AAL technologies in daily use
      considering the entire value chain. Additionally, go-to market strategies for
      assistive technologies based on an involvement of all relevant stakeholders are
      developed. Within this paper an overview of the specific objectives, approaches
      and the status of all Austrian AAL pilot regions is given. Taking into account
      the different experiences of the different pilot regions, specific challenges in
      establishing, implementing and sustaining pilot region projects are discussed and
      lessons-learned are presented. Results show that a careful planning of all
      project phases taking into account available resources is crucial for the
      successful implementation of an AAL pilot region. In particular, this applies to
      all activities related to the active involvement of end-users.

PMID- 28508796
TI  - eMedication Meets eHealth with the Electronic Medication Management Assistant
      (eMMA).
AB  - BACKGROUND: A patient's healthcare team is often missing a complete overview on
      the prescribed and dispensed medication. This is due to an inconsistent
      information flow between the different actors of the healthcare system. Often,
      only the patient himself knows exactly which drugs he is actually taking.
      OBJECTIVES: Our objective is to exploit different eHealth technologies available
      or planned in Switzerland to improve the information flow of the medication data
      among the stakeholder and to support the patient in managing his medication.
      METHODS: This work is embedded in the "Hospital of the Future Live" project,
      involving 16 companies and 6 hospitals in order to develop IT solutions for
      future optimized health care processes. A comprehensive set of requirements was
      collected from the different actors and project partners. Further, specifications
      of the available or planned eHealth infrastructure were reviewed to integrate
      relevant technologies into a coherent concept. RESULTS: We developed a concept
      that combines the medication list and an eHealth platform. The resulting
      electronic medication management assistant (eMMA) designed for the patient
      provides the current medication plan at any time and supports by providing
      relevant information through a conversational user interface. CONCLUSION: In
      Switzerland, we still need a bridging technology to combine the medication
      information from the electronic patient record with the medication plan's
      associated QR-Code. The developed app is intended to provide such bridge and
      demonstrates the usefulness of the eMediplan. It enables the patient to have all
      data regarding his medication on his personal mobile phone and he can - if
      necessary - provide the current medication to the health professional.

PMID- 28508797
TI  - A Web-Based Tool to Evaluate Data Quality of Reused Health Data Assets.
AB  - BACKGROUND: Data from the health care domain is often reused to create and
      parameterize simulation models for example to support life science business in
      the evaluation of new products. Data quality assessments play an important part
      to help model users in interpreting simulation results by showing deficiencies in
      the raw data used in the model building and offers model builders a comparison of
      data quality amongst the used data assets. OBJECTIVES: Assess data quality in raw
      data prior to creating simulation models and prepare results for model users.
      METHODS: Using a literature review and documentation of previous models created,
      we searched data quality criteria. For eligible criteria we formulated questions
      and viable answers to be used in a questionnaire to assess data quality of a data
      asset. RESULTS: We developed a web tool to evaluate data assets using a generic
      data model. Percentage results are visualized using a radar chart. CONCLUSION:
      Data quality assessment with questionnaires offers model builders a framework to
      critically analyse raw data and to detect deficiencies early in the modelling
      process. The summarized results can help model users to better interpret
      simulation results.

PMID- 28508798
TI  - Frequent Treatment Sequence Mining from Medical Databases.
AB  - The huge amount of data stored in healthcare databases allows wide range
      possibilities for data analysis. In this article, we present a novel multilevel
      analysis methodology to generate and analyze sequential healthcare treatment
      events. The event sequences can be generated on different abstraction levels
      automatically from the source data, and so they describe the treatment of
      patients on different levels of detail. To present applicability of the proposed
      methodology, we introduce a short case study as well, in which some analysis
      results are presented arising from the analysis of a group of patients suffering
      from colorectal cancer.

PMID- 28508799
TI  - Comparison of Body Weight Trend Algorithms for Prediction of Heart Failure
      Related Events in Home Care Setting.
AB  - BACKGROUND: Automatic event detection is used in telemedicine based heart failure
      disease management programs supporting physicians and nurses in monitoring of
      patients' health data. OBJECTIVES: Analysis of the performance of automatic event
      detection algorithms for prediction of HF related hospitalisations or diuretic
      dose increases. METHODS: Rule-Of-Thumb and Moving Average Convergence Divergence
      (MACD) algorithm were applied to body weight data from 106 heart failure patients
      of the HerzMobil-Tirol disease management program. The evaluation criteria were
      based on Youden index and ROC curves. RESULTS: Analysis of data from 1460
      monitoring weeks with 54 events showed a maximum Youden index of 0.19 for MACD
      and RoT with a specificity > 0.90. CONCLUSION: Comparison of the two algorithms
      for real-world monitoring data showed similar results regarding total and limited
      AUC. An improvement of the sensitivity might be possible by including additional
      health data (e.g. vital signs and self-reported well-being) because body weight
      variations obviously are not the only cause of HF related hospitalisations or
      diuretic dose increases.

PMID- 28508800
TI  - Electronic Health Records in Prehospital Care.
AB  - Documentation is an essential part and duty in all clinical settings. "ELGA"
      (short for "Elektronische Gesundheitsakte") is the Austrian Electronic Health
      Record and aims to support the process of clinical decision-making. However the
      use case of integrating ELGA to an out-of-hospital setting is not defined yet.
      This work explores the special requirements in prehospital care. The aim of
      research is to identify needed information and processes at the emergency scene
      to establish appropriate decisions about diagnosis, treatments and transport.
      Moreover the mentioned use case should be discussed by mapping available data
      fields in ELGA to the required data at scene. To satisfy the research goal an
      exploratory research using field work and expert interviews was done as well as a
      systematic analysis of findings. The results were analyzed with a thematic
      analysis approach and structured as flow charts, to illustrate the process, and
      as an Entity-Relationship-Model, to show the required data at scene mapped to
      available data fields in ELGA. It was possible to show that ELGA is suitable to
      serve several use cases in prehospital care.

PMID- 28508801
TI  - Adaptive Pump Speed Algorithms to Improve Exercise Capacity in Patients Supported
      with a Left-Ventricular Assist Device.
AB  - For the treatment of terminal heart failure, the therapy with left-ventricular
      assist devices has already been established. In the systems used today, pump
      speed does not adjust during physical activity so that cardiac output and
      exercise capacity remain markedly limited. It is the aim of this study to develop
      an automatic pump speed control based on filling pressure values in order to
      improve exercise capacity and quality of life in these patients. Different
      approaches are planned, to be tested in an in vitro patient simulator. The
      algorithms aim to match the pump speed with the increased venous return. In
      addition, preservation of aortic valve function should be taken into account.

PMID- 28508802
TI  - Knowledge Engineering as a Component of the Curriculum for Medical Cybernetists.
AB  - According to a new state educational standard, students who have chosen medical
      cybernetics as their major must develop a knowledge engineering competency.
      Previously, in the course "Clinical cybernetics" while practicing project-based
      learning students were designing automated workstations for medical personnel
      using client-server technology. The purpose of the article is to give insight
      into the project of a new educational module "Knowledge engineering". Students
      will acquire expert knowledge by holding interviews and conducting surveys, and
      then they will formalize it. After that, students will form declarative expert
      knowledge in a network model and analyze the knowledge graph. Expert decision
      making methods will be applied in software on the basis of a production model of
      knowledge. Project implementation will result not only in the development of
      analytical competencies among students, but also creation of a practically useful
      expert system based on student models to support medical decisions. Nowadays,
      this module is being tested in the educational process.

PMID- 28508804
TI  - eHealth Networking Information Systems - The New Quality of Information Exchange.
AB  - BACKGROUND: The development and introduction of platforms that enable
      interdisciplinary exchange on current developments and projects in the area of
      eHealth have been stimulated by different authorities. OBJECTIVES: The aim of
      this project was to develop a repository of eHealth projects that will make the
      wealth of eHealth projects visible and enable mutual learning through the sharing
      of experiences and good practice. METHODS: The content of the database and search
      criteria as well as their categories were determined in close co-ordination and
      cooperation with stakeholders from the specialist areas. Technically, we used
      Java Server Faces (JSF) for the implementation of the frontend of the web
      application. RESULTS: Access to structured information on projects can support
      stakeholders to combining skills and knowledge residing in different places to
      create new solutions and approaches within a network of evolving competencies and
      opportunities. CONCLUSION: A regional database is the beginning of a structured
      collection and presentation of projects, which can then be incorporated into a
      broader context. The next step will be to unify this information transparently.

PMID- 28508803
TI  - A First Standardized Swiss Electronic Maternity Record.
AB  - BACKGROUND: During the nine months of pregnancy, women have to regularly visit
      several physicians for continuous monitoring of the health and development of the
      fetus and mother. Comprehensive examination results of different types are
      generated in this process; documentation and data transmission standards are
      still unavailable or not in use. Relevant information is collected in a paper
      based maternity record carried by the pregnant women. OBJECTIVES: To improve
      availability and transmission of data, we aim at developing a first prototype for
      an electronic maternity record for Switzerland. METHODS: By analyzing the
      documentation workflow during pregnancy, we determined a maternity record data
      set. Further, we collected requirements towards a digital maternity record. As
      data exchange format, the Swiss specific exchange format SMEEX (swiss medical
      data exchange) was exploited. Feedback from 27 potential users was collected to
      identify further improvements. RESULTS: The relevant data is extracted from the
      primary care information system as SMEEX file, stored in a database and made
      available in a web and a mobile application, developed as prototypes of an
      electronic maternity record. CONCLUSION: The user confirmed the usefulness of the
      system and provided multiple suggestions for an extension. An electronical
      maternity record as developed in this work could be in future linked to the
      electronic patient record.

PMID- 28508805
TI  - Data Quality- and Master Data Management - A Hospital Case.
AB  - Poor data quality prevents the analysis of data for decisions which are critical
      for business. It also has a negative impact on business processes. Nevertheless
      the maturity level of data quality- and master data management is still
      insufficient in many organizations nowadays. This article discusses the
      corresponding maturity of companies and a management cycle integrating data
      quality- and master data management in a case dealing with benchmarking in
      hospitals. In conclusion if data quality and master data are not properly
      managed, structured data should not be acquired in the first place due to the
      added expense and complexity.

PMID- 28508806
TI  - Telemonitoring and Medical Care of Heart Failure Patients Supported by Left
      Ventricular Assist Devices - The Medolution Project.
AB  - Long-term survival after left ventricular assist device (LVAD) implantation in
      heart failure patients is mainly determined by a sophisticated after-care.
      Ambulatory visits only take place every 12 weeks. In case of life-threatening
      complications (pump thrombosis, driveline infection) this might lead to delayed
      diagnosis and delayed intervention. It is the intention of the international
      project Medolution (Medical care evolution) to develop new approaches in order to
      create best structures for telemonitoring of LVAD patients. In the very early
      period of the project a questionnaire was sent to 180 LVAD patients to evaluate
      the need and acceptance of telemonitoring. Thereafter, a graphical user interface
      (GUI) mockup was developed as one of the first steps to improve the continuous
      contact between the LVAD patient and the physician. As a final goal the
      Medolution project aims to bundle all relevant informations from different data
      sources into one platform in order to provide the physician a comprehensive
      overview of a patient's situation. In the systems background a big data analysis
      should run permanently and should try to detect abnormalities and correlations as
      well. At crucial events, a notification system should inform the physician and
      should provide the causing data via a decision support system. With this new
      system we are expecting early detection and prevention of common and partially
      life-threatening complications, less readmissions to the hospital, an increase in
      quality of life for the patients and less costs for the health care system as
      well.

PMID- 28508807
TI  - New Service Excellence Model for eHealth and AAL Solutions - A Framework for
      Continuous New Service Development.
AB  - The development of eHealth and AAL (Ambient Assisted Living) services with the
      aim to reduce the complexity of living environments for the elderly often does
      not lead to the desired results on the market. The design of an eHealth/AAL
      specific framework for continuous New Service Development is presented in this
      paper. Our research addresses this challenge with a new Service Excellence Model
      (SEM) and outlines the benefits of this specific approach. The research is based
      on the data of the DALIA project (Assistant for DAily LIfe Activities at Home)
      and the PenAAL project (Performance Measurement Index for AAL solutions), parts
      of which the projects were the classification of relevant business dimensions and
      the development of a related scoring tool for continuous benchmarking and
      improvement.

PMID- 28508808
TI  - Digital Media for Primary Health Care in Austria.
AB  - Primary health care (PHC) is currently being improved in all developed
      industries. The aim is to make healthcare more patient-centered and close to the
      patient's place of residence. In addition to the organizational and
      interdisciplinary reorientation, the use of digital media is increasingly being
      emphasized. Through literature research and an online survey among Austrian
      doctors and general practitioners, the current and future challenges for the use
      of digital media in networked and regional primary health care were identified
      and prioritized. It becomes clear that basic functions like documentation,
      communication and coordination in the individual medical practice are at the
      forefront. In the future it will be necessary to support regional and
      interprofessional networking through digital media.

PMID- 28508809
TI  - Health Information System in a Cloud Computing Context.
AB  - Healthcare as a worldwide industry is experiencing a period of growth based on
      health information technology. The capabilities of cloud systems make it as an
      option to develop eHealth goals. The main objectives of the present study was to
      evaluate the advantages and limitations of health information systems
      implementation in a cloud-computing context that was conducted as a systematic
      review in 2016. Science direct, Scopus, Web of science, IEEE, PubMed and Google
      scholar were searched according study criteria. Among 308 articles initially
      found, 21 articles were entered in the final analysis. All the studies had
      considered cloud computing as a positive tool to help advance health technology,
      but none had insisted too much on its limitations and threats. Electronic health
      record systems have been mostly studied in the fields of implementation,
      designing, and presentation of models and prototypes. According to this research,
      the main advantages of cloud-based health information systems could be
      categorized into the following groups: economic benefits and advantages of
      information management. The main limitations of the implementation of cloud-based
      health information systems could be categorized into the 4 groups of security,
      legal, technical, and human restrictions. Compared to earlier studies, the
      present research had the advantage of dealing with the issue of health
      information systems in a cloud platform. The high frequency of studies conducted
      on the implementation of cloud-based health information systems revealed health
      industry interest in the application of this technology. Security was a subject
      discussed in most studies due to health information sensitivity. In this
      investigation, some mechanisms and solutions were discussed concerning the
      mentioned systems, which would provide a suitable area for future scientific
      research on this issue. The limitations and solutions discussed in this
      systematic study would help healthcare managers and decision-makers take better
      and more efficient advantages of this technology and make better planning to
      adopt cloud-based health information systems.

PMID- 28508810
TI  - Timed Up-and-Go Device for Unsupervised Functional Assessment of Elderly
      Patients.
AB  - Functional evaluation of elderly patients is one key component in a comprehensive
      Geriatric Assessment. The increased workload and high costs associated to close
      and continuous monitoring in clinical settings may be counterbalanced by the
      application of ICT-supported remote follow-up. Although clinical parameters and
      questionnaires can be supported with smartphones and smart gadgets, physical
      performance trials pose a challenge for community-based approaches with
      difficulties arising from setting up trials, the lack of guidance and
      supervision. We developed an ultrasonic-based device to overcome all of these
      barriers and enable elderly people to perform the Timed Up-and-Go test in an
      autonomous and unsupervised setting. Moreover, we introduce an algorithm to
      verify the successful performance of the test in order to increase the
      reliability of the information provided.

PMID- 28508811
TI  - Disease Monitoring Related Adherence and Its Association with Mortality in Lower
      Austrian Diabetes Patients.
AB  - BACKGROUND: Patient adherence is an important component of an efficient therapy.
      For diabetes patients it may contribute to controlled glucose values and
      reduction of adverse outcomes. OBJECTIVES: We aim to examine a potential
      association of Lower Austrian diabetes patients' adherence concerning their
      disease monitoring and mortality. METHODS: Using a retrospective cohort study
      design, claims data of 55,873 diabetes patients were examined for regular HbA1c
      lab tests that served as a proxy for monitoring related adherence. The cumulative
      incidence of mortality was estimated in the total study population and separately
      for different levels of adherence using the product-limit method. Mortality was
      compared between the different levels of adherence by the log-rank test. RESULTS:
      The cumulative incidence of mortality after one and two years was 4.2% and 8.7%.
      Patients with low adherence had a significantly higher risk of mortality than
      patients with high adherence (p < 0.001). Further results of a multivariable
      analysis will be presented at the conference. CONCLUSION: According to our
      preliminary univariate analysis, monitoring related adherence seems to be
      substantially beneficial for diabetes patients in Lower Austria.

PMID- 28508812
TI  - Comparison of Control Group Generating Methods.
AB  - Retrospective studies suffer from drawbacks such as selection bias. As the
      selection of the control group has a significant impact on the evaluation of the
      results, it is very important to find the proper method to generate the most
      appropriate control group. In this paper we suggest two nearest neighbors based
      control group selection methods that aim to achieve good matching between the
      individuals of case and control groups. The effectiveness of the proposed methods
      is evaluated by runtime and accuracy tests and the results are compared to the
      classical stratified sampling method.

PMID- 28508813
TI  - Web and Mobile Based HIV Prevention and Intervention Programs Pros and Cons - A
      Review.
AB  - BACKGROUND: With the increasing growth of HIV positive people the use of
      information and communication technologies (ICT) can play an important role in
      controlling the spread of the AIDS. Web and Mobile are the new technologies that
      young people take advantage from them. OBJECTIVES: In this study a review to
      investigate the web and mobile based HIV prevention and intervention programs was
      carried out. METHODS: A scoping review was conducted including PubMed, Science
      direct, Web of Science and Proquest to find relevant sources that published in
      2009 to 2016. To identify published, original research that reported the web and
      mobile-based HIV prevention and intervention programs, an organized search was
      conducted with the following search keywords in combination: HIV, AIDS, m-Health,
      Mobile phone, Cell phone, Smartphone, Mobile health, internet, and web. RESULTS:
      Using the employed strategies, 173 references retrieved. Searched articles were
      compared based on their titles and abstracts. To identify duplicated articles,
      the title and abstracts were considered and 101 duplicated references were
      excluded. By going through the full text of related papers, 35 articles were
      found to be more related to the questions of this paper from which 72 final
      included. CONCLUSION: The advantages of web and mobile-based interventions
      include the possibility to provide constancy in the delivery of an intervention,
      impending low cost, and the ability to spread the intervention to an extensive
      community. Online programs such as Chat room-based Education program, Web-based
      therapeutic education system, and Online seek information can use for HIV/AIDS
      prevention. To use of mobile for HIV/AIDS prevention and intervention, programs
      including in: Health system focused applications, Population health focused
      applications, and Health messaging can be used.

PMID- 28508814
TI  - Plausibility of Individual Decisions from Random Forests in Clinical Predictive
      Modelling Applications.
AB  - BACKGROUND: Machine learning algorithms are a promising approach to help
      physicians to deal with the ever increasing amount of data collected in
      healthcare each day. However, interpretation of suggestions derived from
      predictive models can be difficult. OBJECTIVES: The aim of this work was to
      quantify the influence of a specific feature on an individual decision proposed
      by a random forest (RF). METHODS: For each decision tree within the RF, the
      influence of each feature on a specific decision (FID) was quantified. For each
      feature, changes in outcome value due to the feature were summarized along the
      path. Results from all the trees in the RF were statistically merged. The ratio
      of FID to the respective feature's global importance was calculated (FIDrel).
      RESULTS: Global feature importance, FID and FIDrel significantly differed,
      depending on the individual input data. Therefore, we suggest to present the most
      important features as determined for FID and for FIDrel, whenever results of a RF
      are visualized. CONCLUSION: Feature influence on a specific decision can be
      quantified in RFs. Further studies will be necessary to evaluate our approach in
      a real world scenario.

PMID- 28508815
TI  - Bluetooth Low Energy Peripheral Android Health App for Educational and
      Interoperability Testing Purposes.
AB  - Based on recent telemonitoring activities in Austria for enabling integrated
      health care, the communication interfaces between personal health devices (e.g.
      blood pressure monitor) and personal health gateway devices (e.g. smartphone,
      routing received information to wide area networks) play an important role. In
      order to ease testing of the Bluetooth Low Energy interface functionality of the
      personal health gateway devices, a personal health device simulator was
      developed. Based on specifications from the Bluetooth SIG a XML software test
      configuration file structure is defined that declares the specific features of
      the personal health devices simulated. Using this configuration file, different
      scenarios are defined, e.g. send a single measurement result from a blood
      pressure reading or sending multiple (historic) weight scale readings. The
      simulator is intended to be used for educational purposes in lectures, where the
      number of physical personal health devices can be reduced and learning can be
      improved. It could be shown that this simulator assists the development process
      of mHealth applications by reducing the time needed for development and testing.

PMID- 28508816
TI  - Physicians' Use of Online Clinical Evidence in Mashhad University of Medical
      Sciences, Iran.
AB  - The Internet is an important source of medical information. It is expected that
      the use of online sources will improve clinical decisions. This study aims to
      evaluate online information seeking behavior of physicians of Mashhad University
      of Medical Sciences on the use of online clinical evidence. A cross-sectional,
      questionnaire-based study was carried out between November and December 2014 in
      the five academic hospitals. A total of 252 physicians completed the
      questionnaire. The majority of physicians (63.6 of specialists and 58.5% of
      residents) had no internet access in their consultation and visit rooms. The
      majority of physicians (77.8% of specialists and 80% of residents) respectively
      used Google, as well as 67.5% specialists and 52.2% residents always used Medline
      or PubMed, among electronic sources, to searching for information. The main
      reasons for physicians' dissatisfaction with the Internet, as a source of health
      information, were lack of access to medical sources owing to the non-targeted
      filtering (61% specialists and 74.6% residents) and very slow connection of the
      Internet (75.6% specialists and 83.1% residents). It is recommended that medical
      informatics training programs should be incorporated, where physicians are
      required to search for health information in the Internet.

PMID- 28508817
TI  - Development of and Adherence to a Computer-Based Gamified Environment Designed to
      Promote Health and Wellbeing in Older People with Mild Cognitive Impairment.
AB  - BACKGROUND: The older population of Europe is increasing and there has been a
      corresponding increase in long term care costs. This project sought to promote
      active ageing by delivering tasks via a tablet computer to participants aged 65
      80 with mild cognitive impairment. OBJECTIVES: An age-appropriate gamified
      environment was developed and adherence to this solution was assessed through an
      intervention. METHODS: The gamified environment was developed through focus
      groups. Mixed methods were used in the intervention with the time spent engaging
      with applications recorded supplemented by participant interviews to gauge
      adherence. There were two groups of participants: one living in a retirement
      village and the other living separately across a city. RESULTS: The retirement
      village participants engaged in more than three times the number of game sessions
      compared to the other group possibly because of different social arrangements
      between the groups. CONCLUSION: A gamified environment can help older people
      engage in computer-based applications. However, social community factors
      influence adherence in a longer term intervention.

PMID- 28508818
TI  - Biosignals, Standards and FHIR - The Way to Go?
AB  - BACKGROUND: Standards have become available to share semantically encoded vital
      parameters from medical devices, as required for example by personal healthcare
      records. Standardised sharing of biosignal data largely remains open. OBJECTIVES:
      The goal of this work is to explore available biosignal file format and data
      exchange standards and profiles, and to conceptualise end-to-end solutions.
      METHODS: The authors reviewed and discussed available biosignal file format
      standards with other members of international standards development organisations
      (SDOs). RESULTS: A raw concept for standards based acquisition, storage,
      archiving and sharing of biosignals was developed. The GDF format may serve for
      storing biosignals. Signals can then be shared using FHIR resources and may be
      stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible
      format. CONCLUSION: Currently a group of international SDOs (e.g. HL7, IHE,
      DICOM, IEEE) is engaged in intensive discussions. This discussion extends
      existing work that already was adopted by large implementer communities. The
      concept presented here only reports the current status of the discussion in
      Austria. The discussion will continue internationally, with results to be
      expected over the coming years.

PMID- 28508819
TI  - 128 SHADES OF RED: Objective Remote Assessment of Radiation Dermatitis by
      Augmented Digital Skin Imaging.
AB  - The purpose of our investigation was to develop a novel and state of the art
      digital skin imaging method capable for remote monitoring and objective
      assessment of Radiation Induced Dermatitis (RID). Therefore, radiation therapy
      related side effects were assessed by medical experts according to Common
      Terminology Criteria for Adverse Events (CTCAE) grade of severity in 20 female
      breast cancer patients in a clinical trial over the treatment time frame of 25-28
      radiation cycles, 50.0-50.4 Gy each. Furthermore the intensity of developed skin
      erythema was documented by using conventional spectrophotometry plus digital skin
      imaging. Thereby we could derive the Standardized Erythema Value (SEV), a novel
      objective parameter, which in contrast to single parametric L* and a* delivers a
      long dynamic measurement range for analyzing RID from bright to very dark skin
      tones. Methodical superiority of the SEV could be proven over spectrophotometer
      measurements in terms of a higher sensitivity and by enabling signal intensity
      mapping in analyzed skin images. Our thereupon-derived patent enables novel
      objective dermatologic eHealth applications in a broad range of medical and
      industrial use by opening likewise the window for augmented dermatology. The
      first of its kind system is now already further developed in form of the medical
      device product Scarletred<sup>(r)</sup>Vision. It is available on the market for
      primary usage in clinical trials and in medical routine.

PMID- 28508820
TI  - Developing Interactive Plug-ins for tranSMART Using the SmartR Framework: The
      Case of Survival Analysis.
AB  - BACKGROUND: TranSMART has become an important and widely used platform for the
      translational research. Included features for analysing data have significant
      deficiencies concerning user interactivity with and export of the generated
      results. SmartR, a plugin for tranSMART, promises to close this gap with its
      interactive workflows. OBJECTIVES: Test with a proof of concept whether an own
      SmartR workflow is possible. Improvement of the integrated survival analysis with
      a self-build workflow, taking specific user requirements into account. METHODS:
      Analysis of existing SmartR workflows to understand the underlying SmartR
      architecture. Implementation of a SmartR workflow, which provides an improved
      survival analysis. RESULTS: Extension of SmartR and thus tranSMART is possible
      and could be successfully achieved with a prototype for survival analysis. The
      framework still lacks some functionality, like binning of continuous variables,
      and documentation. CONCLUSION: SmartR workflows are a good way for realising
      interactive analysis, but the SmartR framework still needs further improvements
      to become a full alternative to the already existing Rmodules.

PMID- 28508821
TI  - Measuring the Negative Impact of Long Sitting Hours at High School Students Using
      the Microsoft Kinect.
AB  - This paper suggests the usage of the Microsoft Kinect to detect the onset of the
      scoliosis at high school students due to incorrect sitting positions. The
      measurement is done by measuring the overall posture in orthostatic position
      using the Microsoft Kinect. During the measuring process several key points of
      the human body are tracked like the hips and shoulders to form the postural data.
      The test was done on 30 high school students who spend 6 to 7 hours per day in
      the school benches. The postural data is statistically processed by IBM Watson's
      Analytics. From the statistical analysis we have obtained that a prolonged
      sitting position at such young ages affects in a negative way the spinal cord and
      facilitates the appearance of malicious postures like scoliosis and lordosis.

PMID- 28508824
TI  - From the editor.

PMID- 28508825
TI  - ABCs of RhoGTPases indicating potential role as oncotargets.
AB  - RhoGTPases also known as molecular switches represent a family of GTP-binding
      proteins. They shuttle between "On" and "Off" states. In the "On" state, they
      activate plethora of molecules. These proteins perform a wide variety of
      functions involving cytoskeletal modeling, cell motility, migration, and mitosis.
      Members of this family are referred as master regulators of many cellular
      activities. Due to wide variety of portfolios attributed to RhoGTPases, their
      misbehavior leads to initiation and also progression of metastatic cancers. Many
      members of this family have been reported to be differentially regulated leading
      to spread of malignant cells from one site to other. These wandering cells find a
      comfortable site in accordance to Paget's soil and seed hypothesis and form
      secondary lesions. Out of multiple members of this family, RhoA and RhoC are
      important factors. RhoA is supposed to increase tumor proliferation when
      overexpressed while RhoC is responsible for tumor initiation. We searched
      publications on RhoGTPases, their functions and contribution in cancer
      development and metastasis on World Wide Web and PubMed. This review focuses on
      the role of Rac and Rho small GTPases in cell motility and granting the
      opportunistic motile behavior of aggressive cancer cells. To condense knowledge
      from existing literature about the roles played by these molecular switches,
      their structural and functional ramifications are introduced in the beginning
      followed by an account on their wrong behavior that leads to oncogenesis and
      oncoprogression. This piece of work highlights members of RhoGTPases as viable
      oncotargets.

PMID- 28508826
TI  - Genomic aberrations in non- small cell lung cancer and their impact on treatment
      outcome.
AB  - The therapeutic options of nonsmall cell lung cancer (NSCLC) therapy has been
      changed since the first discovery of activating epidermal growth factor receptor
      (EGFR) mutations and the development of specific EGFR tyrosine kinase inhibitors,
      which resulted in the evolution of "personalized medicine." There are a
      considerable number of genomic aberrations in NSCLC serving as potential
      predictive biomarkers and drug targets and still more. We summarized the
      molecular pathways, potential targets, and possible impact on disease outcome in
      NSCLC.

PMID- 28508827
TI  - Multiple primary malignant neoplasms: A 10-year experience at a single
      institution from Turkey.
AB  - PURPOSE: The development of improved diagnostic techniques, increased survival,
      and life expectancy of cancer patients have all contributed to the higher
      frequency of multiple primary malignant neoplasms (MPMN). MPMN can be divided
      into two main categories: Synchronous MPMN (sMPMN) and metachronous MPMN (mMPMN).
      MATERIALS AND METHODS: 122 patients with MPMN analyzed retrospectively who were
      admitted to the Radiation Oncology Department of Eskisehir Osmangazi University
      Medical Faculty from January 2004 to December 2013. The patient characteristics
      and relation with overall survival (OS) were examined. RESULTS: The overall
      incidence of MPMN was found 1.2% in our institution. The median age was 59
      (range: 29-80) years. Male:female ratio was 54.5:45.5%, and mMPMN:sMPMN ratio was
      69.9:30.1%. The most common 3 cancers were head and neck (22%), breast (20%), and
      gastrointestinal (20%) for first primary; and gastrointestinal (22%), lung (19%),
      gynecologic tumors (15%) for second primary cancers, respectively. The median OS
      in patients with sMPMN and mMPMN were 30 (3-105) and 91 (4-493) months. 2, 3, and
      5 years OS of patients with sMPMN were 86%, 75%, 63%, and with mMPMN were 92%,
      88%, 80%, respectively (P < 0.005). CONCLUSION: OS was found longer in female
      patients with sMPMN (P < 0.05), and in all group with mMPMN (P < 0.005).

PMID- 28508828
TI  - Evaluation of role of alpha-methyl acyl-coenzyme A racemase/P504S and high
      molecular weight cytokeratin in diagnosing prostatic lesions.
AB  - BACKGROUND: In recent years basal cell markers (high molecular weight cytokeratin
      [HMWCK]) and prostate biomarker alpha-methyl acyl-coenzyme A racemase (AMACR)
      have been used as adjuvant to morphology in diagnostically challenging cases with
      a very high sensitivity and specificity. This has increased the diagnostic
      accuracy of prostate cancer worldwide. MATERIALS AND METHODS: In this prospective
      study, total of 50 cases including 37 cases of malignant lesions and 13 cases of
      benign lesions of the prostate were taken. Tumor grade was determined according
      to Gleason's grading system. AMACR and HMWCK expressions were determined by
      immunohistochemical staining. The obtained results were analyzed and evaluated
      using Chi-square statistical test (SPSS version 20). RESULTS: AMACR was not
      expressed in any of the 13 cases of benign lesions of the prostate while in
      malignant lesions of prostate it was expressed in 33 of 37 (89.18%) cases. All 4
      (100%) cases of well-differentiated carcinoma were positive for AMACR expression.
      21 of 25 (84%) moderately differentiated and all 10 (100%) cases of poorly
      differentiated tumors were positive for AMACR. There was statistically
      significant difference in expression of AMACR between benign and malignant
      lesions of the prostate, indicated byP = 0.001. In benign lesions, HMWCK was
      expressed in all the 13 (100%) cases while in malignant lesions of prostate it
      was not expressed in any of the (0%) case. All 13 benign lesions were positive
      for HMWCK only. AMACR expression was not seen in any of the benign lesion. Out of
      37 malignant cases, 4 cases were negative for both, 33 cases were positive only
      for AMACR, but no case was positive only for HMWCK. CONCLUSIONS: As an adjunct to
      biopsy, AMACR and HMWCK have value for resolving diagnostically challenging
      cases.

PMID- 28508829
TI  - The association between rs1972820 and the risk of breast cancer in Isfahan
      population.
AB  - CONTEXT: A number of single nucleotide polymorphisms (SNPs) in ERBB4 gene have
      been linked to increase the risk of breast cancer. However, no study has been
      dedicated to analyze the significance of microRNA-related SNP rs1972820, located
      in ERBB4 3'-untranslated region (UTR), in breast tumors. AIMS: Here, we
      investigated the frequency and association between rs1972820 and breast cancer.
      SUBJECTS AND METHODS: The rs1972820 genotypes in 182 samples were collected from
      96 healthy people, and 86 breast cancer patients were determined using tetra
      primer amplification refractory mutation system-polymerase chain reaction. The
      frequency of genotypes was analyzed to find the association between rs1972820 and
      breast cancer risk. STATISTICAL ANALYSIS USED: Conditional logistic regression,
      odds ratios (ORs), the associated 95% confidence intervals (CIs), and Armitage's
      test were used in this study. RESULTS: In silico analysis suggested that
      rs1972820 located in the 3'UTR of ERBB4 gene affects the binding affinity of miR
      3144-3p a potential oncomiRNA. Statistical analysis showed a significant
      association between SNP rs1972820 G allele and reduced breast cancer risk, odds
      ratio = 0.443 (95% CI: 0.196-0.998). CONCLUSIONS: rs1972820 SNP allele is
      significantly associated with the reduced risk of breast cancer and could be
      considered as a potential marker for breast cancer predisposition in population
      of Isfahan.

PMID- 28508830
TI  - Dosimetric verification of dose calculation algorithm in the lung during total
      marrow irradiation using helical tomotherapy.
AB  - INTRODUCTION: Treatment of proliferative diseases of the hematopoietic system
      involves, in most cases, chemotherapy combined with radiation therapy, which is
      intended to provide adequate immunosuppressant. Conventionally, total body
      irradiation (TBI) was used; however, total marrow irradiation (TMI) performed
      with helical tomotherapy (HT) has been proposed as an alternative, with the aim
      of delivering the highest dose in the target area (skeleton bone). PURPOSE: The
      purpose of this study is to evaluate the accuracy of the dose calculation
      algorithm for the lung in TMI delivered with HT. METHODS: Thermoluminescent
      detectors (TLD-100 Harshaw) were used to measure delivered doses. Doses were
      calculated for 95 selected points in the central lung (53 TLDs) and near the rib
      bones (42 TLDs) in the anthropomorphic phantom. A total of 12 Gy were delivered
      (6 fractions of 2 Gy/fraction). RESULTS: HT-TMI technique reduces the dose
      delivered to the lungs in a phantom model to levels that are much lower than
      those reported for TBI delivered by a conventional linear accelerator. The mean
      calculated lung dose was 5.6 Gy versus a mean measured dose of 5.7 +/- 2.4 Gy.
      The maximum and minimum measured doses were, respectively, 11.3 Gy (chest wall)
      and 2.8 Gy (central lung). At most of the 95 points, the measured dose was lower
      than the calculated dose, with the largest differences observed in the region
      located between the target volume and the adjacent lung tissue. The mean measured
      dose was lower than the calculated dose in both primary locations: -3.7% in the
      42 rib-adjacent detectors and -3.0% in the 53 central lung TLDs. CONCLUSION: Our
      study has shown that the measured doses may be lower than those calculated by the
      HT-TMI calculation algorithm. Although these differences between calculated and
      measured doses are not clinically relevant, this finding merits further
      investigation.

PMID- 28508831
TI  - Dual phase cone-beam computed tomography in detecting <3 cm hepatocellular
      carcinomas during transarterial chemoembolization.
AB  - OBJECTIVE: The objective of this study was to evaluate the sensitivity of dual
      phase cone-beam computed tomography (CBCT) in detecting small (<3 cm in diameter)
      hepatocellular carcinoma (HCC) tumors during transarterial chemoembolization
      (TACE). MATERIALS AND METHODS: Twenty-two consecutive patients with unresectable
      small HCCs in whom TACE was performed were retrospectively evaluated. Contrast CT
      or contrast magnetic resonance imaging (MRI) was performed in all patients within
      1 month prior to the procedure. Dual phase CBCT was performed prior to TACE and
      lipiodol-CBCT was performed after treatment. The sensitivity of dual phase CBCT
      in detecting small HCCs was compared to hepatic angiography, contrast enhanced CT
      and MRI. RESULTS: Seventy HCC tumors with sizes of P < 0.001). CONCLUSIONS: Dual
      phase CBCT is significantly more sensitive than hepatic angiography, contrast
      enhanced CT, and MRI in detecting smaller than 3 cm HCC tumors and can be a
      helpful modality in making accurate planning for treatment of HCC.

PMID- 28508832
TI  - Disease characteristics and treatment attributes of patients admitted to the
      oncology ward of a tertiary care government hospital.
AB  - BACKGROUND: The burden of oncology patients in the most developing countries
      including India has witnessed a steady, progressive, and significant upward trend
      attributed mainly to increased life span, availability of better imaging
      modalities, increased awareness, and lifestyle and environmental changes. The
      management of such patients in government setup often presents lots of challenges
      such as advanced stage of presentation, existence of medical comorbid conditions,
      scarcity of beds, and long multimodal treatment often complicated with therapy
      induced toxicities. MATERIALS AND METHODS: A prospective study was undertaken in
      a Radiation Oncology ward catering to male patients over 6-month duration in a
      superspecialty hospital of defense services. The clinical, pathological, and
      treatment-related attributes were recorded. Wherever possible, the clinical
      course of stay, complications during admission, and the response to primary
      management were studied. RESULTS: A total of 570 patients were admitted for 6
      month duration. Of these patients, 240 were transferred in from other peripheral
      service hospitals while the remaining were admitted directly from this hospital
      or transferred from various wards of this hospital. The mean age of the patients
      was 46.5 years. Most common histology was squamous cell carcinoma. The most
      common site of primary was head and neck, followed closely by central nervous
      system tumors and gastrointestinal tract. A total of 185 patients were fresh
      cases admitted for workup and complete duration of definitive management (of
      which 82 received concurrent chemoradiation), 280 patients were for follow-up, 70
      patients were admitted briefly for supportive care during a while on
      chemoradiation, and 15 patients were admitted for administrative reasons. Fifty
      eight patients developed Grade II and onward therapy-induced hematological,
      gastrointestinal, cutaneous complications, and 14 patients suffered from febrile
      neutropenia. Thirty patients developed other significant complications warranting
      cross-referrals to other specialists. One hundred and thirty patients underwent
      more than one imaging modalities (contrast-enhanced computed tomography, magnetic
      resonance imaging, bone scan, and positron emission tomography-computed
      tomography). The duration of stay varied from 3 to 64 days, with an average
      duration of 38 days. There were 18 deaths during the study period. CONCLUSION:
      The course of hospitalization for oncology cases is often prolonged and
      complicated by significant complications, warranting aggressive supportive care
      by various concerned specialists. These patients often require multiple imaging
      for primary and metastatic workup. There is a need for judicious selection of
      patients meriting admission for optimum utilization of existing resources.

PMID- 28508833
TI  - Radiation-induced non-targeted effect in vivo: Evaluation of cyclooygenase-2 and
      endothelin-1 gene expression in rat heart tissues.
AB  - AIM: In this study, we investigated expression levels of cyclooxygenase-2 (COX-2)
      and endothelin-1 (ET-1) genes after pelvis and heart irradiation in a rat model.
      These factors are involved in heart diseases (HDs). MATERIALS AND METHODS: We
      used seven groups, including two groups of pelvic irradiation, two groups of
      whole body irradiation, two groups of heart irradiation, and one control
      nonirradiated group. Pelvis irradiations were conducted at a 2 cm * 2 cm in the
      pelvis area. Irradiation condition conducted using 1.25 MeV cobalt-60 gamma-rays
      (30 cGy/min). The changes at ET-1 and COX-2 gene expressions in heart tissue
      after pelvis and heart irradiation were measured and compared to the control and
      whole body irradiation groups at 24 h and 72 h after the exposure. RESULTS: In
      heart irradiation groups, 3-fold up-regulation of both ET-1 and COX-2 was
      observed. In pelvis irradiation groups, 3-fold up-regulation of ET-1 was seen,
      but not significant changes in COX-2 gene expression have observed at distant
      heart tissues after pelvis irradiation. CONCLUSION: This study reveals that
      nontargeted effect induced by radiation may be considered as an important
      phenomenon for induction of HD after radiotherapy.

PMID- 28508834
TI  - A dosimetric analysis of cardiac dose with or without active breath coordinator
      moderate deep inspiratory breath hold in left sided breast cancer radiotherapy.
AB  - BACKGROUND AND AIM: Cardiac toxicity is a major concern for left breast
      tangential field irradiation. The left ventricle and left anterior descending
      (LAD) artery are suggested to be radiosensitive and radiation to these structures
      leads to late lethal cardiotoxicity. Moderate deep inspiration breath hold
      (mDIBH) during radiation treatment delivery helps in reducing the cardiac dose.
      This study compares dosimetric parameters of heart with and without active breath
      coordinator (ABC) mDIBH during tangential field breast cancer radiation. STUDY
      TYPE: This is a dosimetric comparative study. MATERIALS AND METHODS: Forty-five
      consecutive patients with left-sided breast cancer who underwent breast
      conserving surgery and adjuvant tangential field and radiotherapy with ABC mDIBH
      between November 2013 and September 2015 in our center were analyzed in this
      study. The ABC device was used for respiratory control and patients who could
      hold their breath for 20-30 s were considered for radiation with ABC mDIBH.
      Simulation scans of both free breathing (FB) and ABC mDIBH were done. Tangent
      field treatment plans with a dose prescription of 40 Gy/15 Fr were generated for
      each patient, in both scans. Target coverage, dose to the heart, LAD, and the
      left lung were documented with dose-volume histograms. RESULTS: Statistical
      Package for the Social Sciences, version 20 software, was used for analysis and
      the level of significance was set at P < 0.05. Mean heart dose was 308.5cGy with
      FB and 159cGy with ABC (P < 0.0001). Mean dose to the LAD was reduced by 53.81%
      (1320.64 cGy vs. 606.56 cGy, P < 0.001). Target coverage was equal in both the
      plans. CONCLUSION: We report that the use of ABC mDIBH technique resulted in a
      significant reduction in cardiac dose and hence can be considered as a promising
      tool for cardiac sparing.

PMID- 28508835
TI  - Beneficial influence of ellagic acid on biochemical indexes associated with
      experimentally induced colon carcinogenesis.
AB  - OBJECTIVE: To elucidate the key biochemical indexes associated with 1, 2
      dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy
      of a dietary polyphenol, ellagic acid (EA). MATERIALS AND METHODS: Wistar rats
      were chosen to study objective, and were divided into 4 groups; Group 1-control
      rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group
      3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH
      induced Group 4 rats were initiated with EA treatment. We examined key citric
      acid cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate
      dehydrogenase, succinate dehydrogenase, malate dehydrogenase and the activities
      of respiratory chain enzymes NADH dehydrogenase and Cytochrome-C-oxidase and
      membrane-bound enzyme profiles (Na +/K + ATPase, Ca 2+ ATPase and Mg 2+ ATPase),
      activities of lysosomal proteases such as beta-D-glucuronidase, beta
      galactosidase and N-acety-beta-D-glucosaminidase and cellular thiols (oxidized
      glutathione, protein thiols, and total thiols). RESULTS: It was found that
      administration of DMH to rats decreased both mitochondrial and membrane-bound
      enzymes activities, increased activities of lysosomal enzymes and further
      modulates cellular thiols levels. Treatment with EA significantly restored the
      mitochondrial and ATPases levels and further reduced lysosomal enzymes to near
      normalcy thereby restoring harmful effects induced by DMH. CONCLUSION: EA
      treatment was able to effectively restore the detrimental effects induced by DMH,
      which proves the chemoprotective function of EA against DMH-induced experimental
      colon carcinogenesis.

PMID- 28508836
TI  - Tabulated square-shaped source model for linear accelerator electron beam
      simulation.
AB  - CONTEXT: Using this source model, the Monte Carlo (MC) computation becomes much
      faster for electron beams. AIMS: The aim of this study was to present a source
      model that makes linear accelerator (LINAC) electron beam geometry simulation
      less complex. SETTINGS AND DESIGN: In this study, a tabulated square-shaped
      source with transversal and axial distribution biasing and semi-Gaussian spectrum
      was investigated. SUBJECTS AND METHODS: A low energy photon spectrum was added to
      the semi-Gaussian beam to correct the bremsstrahlung X-ray contamination. After
      running the MC code multiple times and optimizing all spectrums for four electron
      energies in three different medical LINACs (Elekta, Siemens, and Varian), the
      characteristics of a beam passing through a 10 cm * 10 cm applicator were
      obtained. The percentage depth dose and dose profiles at two different depths
      were measured and simulated. RESULTS: The maximum difference between simulated
      and measured percentage of depth doses and dose profiles was 1.8% and 4%,
      respectively. The low energy electron and photon spectrum and the Gaussian
      spectrum peak energy and associated full width at half of maximum and transversal
      distribution weightings were obtained for each electron beam. The proposed method
      yielded a maximum computation time 702 times faster than a complete head
      simulation. CONCLUSIONS: Our study demonstrates that there was an excellent
      agreement between the results of our proposed model and measured data;
      furthermore, an optimum calculation speed was achieved because there was no need
      to define geometry and materials in the LINAC head.

PMID- 28508837
TI  - Colorectal cancer presenting as bone metastasis.
AB  - INTRODUCTION: Bone metastasis is a rare site of metastasis, seen in only 3.7-11%
      of clinical cases. Isolated bone involvement has been reported very rarely in
      literature. Moreover, the patients who have bone metastasis at presentation are
      even rare. OBJECTIVES: To discuss the demographic characteristics,
      carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their
      correlation with survival in patients of colorectal cancer that have bone
      metastasis at the time of presentation. MATERIALS AND METHODS: Retrospectively,
      tumor registry was analyzed for the cases of colorectal cancer presenting with
      bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan
      Meier method and analyzed using the log-rank test. RESULTS: Ten such patients
      were identified (male:female = 7:3) of the total 410 patients. Median age was 41
      years (22-50 years). All patients were Conclusions: In this study, the patients
      of colorectal cancer presenting with bone metastasis were of male sex and younger
      age. The factors that were associated with reduced survival were extraosseous and
      liver involvement.

PMID- 28508838
TI  - Randomized controlled Phase III study comparing hepatic arterial infusion with
      systemic chemotherapy after curative resection for liver metastasis of colorectal
      carcinoma: JFMC 29-0003.
AB  - BACKGROUND: The feasibility and efficacy of adjuvant hepatic arterial infusion
      (HAI) in preventing the development of liver metastases in patients with advanced
      colon carcinoma have not been validated. The aim of this randomized controlled
      study was to compare the feasibility of HAI and the protective effect against
      liver metastasis after curative resection to those of systemic chemotherapy.
      METHODS: Between July 2000 and June 2003, 91 patients were enrolled. Patients
      were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous
      infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary
      endpoint was overall survival (OS). RESULTS: In the WHF group, the cumulative
      failure rate of hepatic arterial catheterization was 16.7% at 6 months. The
      occurrence of grade 3 adverse events was comparable between the groups. The 5
      year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164).
      CVI tended to show a protective effect against liver metastasis regarding the 5
      year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P =
      0.037). CONCLUSION: HAI therapy has a certain protective effect against liver
      metastasis after curative resection in patients with colorectal cancer. However,
      this therapy did not contribute to any marked improvement in their overall
      survival.

PMID- 28508839
TI  - Application of National Cancer Institute recommended terminology in breast
      cytology.
AB  - BACKGROUND: There is a lack of uniformity with regard to the reporting
      terminology used in breast cytology by pathologists worldwide, resulting in
      miscommunication of results among health-care providers. AIM: The present study
      was aimed to assess the accuracy of fine-needle aspiration cytology (FNAC) in the
      evaluation of breast lesions using the National Cancer Institute (NCI)
      recommended terminology. MATERIALS AND METHODS: In this prospective study, a
      total number of 523 breast FNACs were categorized according to the NCI
      guidelines. Of these, 286 (54.7%) had histopathological follow-up, and their FNAC
      diagnoses were compared. The sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) along with 95% confidence interval
      (95% CI) and accuracy of FNAC were calculated. RESULTS: Among 286 FNAC cases, 4
      were unsatisfactory (C1), 188 were benign (C2), 11 were atypical, probably benign
      (C3), 21 were suspicious, favor malignancy (C4), and 62 were malignant (C5). On
      histopathological examination of categories C2 and C3 (total of 199 cases), 193
      were confirmed as benign (true negative) and remaining 6 cases were turned out to
      malignant (false negative). Among categories C4 and C5 (total of 83 cases), 81
      were confirmed as malignant (true positive) and remaining 2 were turned out to be
      benign (false positive). The sensitivity, specificity, PPV, NPV, and accuracy of
      FNAC were 93.1% (95% CI, 88.2%-95%), 99% (95% CI, 96.8%-99.8%), 97.6% (95% CI,
      92.5%-99.6%), 97% (95% CI, 94.9%-97.8%), and 97.2%, respectively. CONCLUSION: Our
      study concluded that FNAC reporting using NCI guidelines highly correlated with
      the histopathological diagnosis.

PMID- 28508840
TI  - Comparison of beam hardening effect of physical and enhanced dynamic wedges at
      bladder inhomogeneity using EBT3 film dosimeter.
AB  - INTRODUCTION: Using physical wedges (PWs) to modify dose distribution and more
      homogeneous target coverage is a well-established technique. However, there are
      many problems with PWs known as beam hardening, which made them problematic. This
      can be overcome by dynamic wedges which do not filter beam. Comparison of
      physical properties of physical and enhanced dynamic wedges (EDWs) restricted to
      homogeneous medium. Hence, the main aim of this study is to compare dosimetric
      properties of physical and EDWs at bladder inhomogeneous phantom as a most common
      case implementing wedges. MATERIALS AND METHODS: An inhomogeneous pelvic phantom
      with homogeneities of uterus, femur, soft tissue, rectum, and bladder was
      designed. Eclipse treatment planning system with the aim of bladder target was
      used for calculations. All dose distributions were measured with EBT3 films.
      RESULTS: Comparison between beam profiles of physical and EDWs at wedged and
      nonwedged directions shows a greater difference at near inhomogeneous soft tissue
      interface and also at heel side of wedges. CONCLUSION: Little difference observed
      between dose distribution of physical and EDWs shows neglectable effect of beam
      hardening produced by PW compared to EDW at inhomogeneous medium. Furthermore,
      EBT3 films present good feature to measure dose distributions at EDW fields.

PMID- 28508841
TI  - Morbidity of central compartment clearance: Comparison of lesser versus complete
      clearance in patients with thyroid cancer.
AB  - BACKGROUND: Extent of central compartment neck dissection (CCND) in thyroid
      cancers has been a debate because of associated morbidity. There have been
      attempts to reduce the extent of surgery in an attempt to decrease morbidity.
      PATIENTS AND METHODS: We analyzed the morbidity of CCND from our prospectively
      maintained surgical morbidity database. CCND was divided into bilateral complete
      clearance (BCC) and less than complete clearance (LCC). LCC was performed for
      clinicoradiologically node negative patients. Rates of hypocalcemia and recurrent
      laryngeal nerve (RLN) palsy rates were compared for LCC versus BCC. We also
      classified procedures performed in the central neck according to the extent of
      dissection. RESULTS: Of 153 evaluable patients, BCC was performed in 43.8% and
      LCC in 56.2%. Rate of postoperative hypocalcemia was 40.2% in BCC group versus
      17.4% in LCC group. We had an overall RLN palsy rate of 7.4%. There was no
      significant difference in RLN palsy rates between the groups. CONCLUSION: Lesser
      extent of dissection in central compartment reduces postoperative hypocalcemia
      but has no influence on RLN palsy rates.

PMID- 28508842
TI  - A3 adenosine receptor agonist induce G1 cell cycle arrest via Cyclin D and cyclin
      dependent kinase 4 pathways in OVCAR-3 and Caov-4 cell lines.
AB  - AIM OF THE STUDY: The cell cycle, a vital process that involves in cells' growth
      and division, lies at the heart of cancer. It has been shown that IB-MECA, an A3
      adenosine receptor agonist inhibits the proliferation of cancer cells by inducing
      cell cycle arrest in several tumors. In this study, we evaluated the role of IB
      MECA inhibition in cell cycle progression in ovarian cancer cells. MATERIALS AND
      METHODS: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay in Caov-4 and OVCAR-3. Analysis of cell cycle
      distribution was carried out by flow cytometry. To determine the mechanisms of IB
      MECA-mediated induction of cell cycle arrest, the expression of cell cycle
      regulatory proteins Cyclin D1 and cyclin-dependent kinase 4 (CDK4) was evaluated.
      RESULTS: Our results showed that IB-MECA significantly reduced cell viability in
      a dose-dependent manner. Moreover, our results indicated that a low concentration
      of IB-MECA induced G1 cell cycle arrest. Reduction of Cyclin D1 and CDK4 protein
      levels was also observed after treating cancer cells with IB-MECA. CONCLUSION:
      This study demonstrated that IB-MECA induces G1 phase cell cycle arrest through
      Cyclin D1/CDK4-mediated pathway in ovarian cancer cells.

PMID- 28508843
TI  - Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post
      chemoradiotherapy.
AB  - BACKGROUND: Concurrent chemoradiotherapy (CCRT) used for definitive management of
      locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ
      preservation at the cost of preservation of function. Vocal cords, being within
      the field of irradiation, undergo acute and chronic changes which adversely
      impacts the patients' voice. AIMS: To assess the acute changes in the acoustic
      characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC. MATERIALS
      AND METHODS: Thirty patients with HNSCC treated with CCRT, a total dose of 66-70
      Gy/33-35 fractions at five fractions/week, with weekly cisplatin. Acoustic
      analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3
      months post-CCRT. Statistical analysis of the parameters using ANOVA and
      Student's t-test was performed. RESULTS: Of the thirty patients, 26 patients
      completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%])
      developed Grade III toxicity. On AA, both increase and decrease in mean F0 from
      baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and
      noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14
      available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for
      both genders; jitter and shimmer, and NHR values maintained an increase (P >
      0.05). CONCLUSIONS: Periodic AA allows quantification of voice changes and
      mapping of vocal toxicity induced by CCRT.

PMID- 28508844
TI  - Evaluation of the effect of temperature variation on response of PRESAGE(r)
      dosimeter.
AB  - INTRODUCTION: Many factors, such as PRESAGE (r) composition, dose rate, energy,
      and type of radiation, temperature, etc., may effect on PRESAGE (r) dosimeter
      response. The aim of this study was investigating the effect of temperature
      variation on response of PRESAGE (r) solid dosimeter. MATERIALS AND METHODS: In
      this study, a PRESAGE (r) solid detector was fabricated. Ninety-four percent
      weight polyurethane, 5% weight carbon tetrachloride, and 1% weight leucomalachite
      green were used. Radiological and physical characteristics of PRESAGEs (r), such
      as mass density, electron density, and effective number atomic were obtained and
      compared with water. Response of PRESAGE (r) dosimeter in temperatures -4, 10,
      25, 35, 45, 55, 65, 75, 85, and 90 degrees C was evaluated. In addition, the
      absorption peak at various temperatures was investigated. RESULTS: The results
      showed that the absorption peak at different temperatures was in the range of 630
      635 nm. For temperatures below 75 degrees C, the results indicated that
      temperature variation has no effect on the response of PRESAGE (r) dosimeter
      whereas at the temperatures> 75 degrees C, temperature variation has an effect on
      PRESAGE (r) dosimeter response. CONCLUSION: The finding showed that temperature
      changes have not impact on the absorption peak. In addition, the results related
      to the effect of temperature variation on the response of PRESAGE (r) dosimeter
      showed that in the range of clinical applications (temperatures below 75 degrees
      C), temperature variation has no effect on PRESAGE (r) dosimeter response.

PMID- 28508845
TI  - Dosimetric comparison of head and neck cancer patients planned with multivendor
      volumetric modulated arc therapy technology.
AB  - AIM: Purpose of this study is to dosimetrically compare head and neck (H and N)
      cancer patients planned with multivendor volumetric modulated arc therapy (VMAT)
      technology. VMAT treatment planning can be done using biological (treatment
      planning system [TPSB]: Monaco) or physical (TPSP: Eclipse)-based cost function
      optimization techniques. Planning and dosimetric comparisons were done in both
      techniques for H and N cases. MATERIALS AND METHODS: Twenty H and N patients were
      retrospectively selected for this study. VMAT plans were generated using TPSP
      (V11.0) and TPSB (V3.0) TPS. A total dose of 66 Gy (planning target volume 1
      [PTV1]) and 60 Gy (PTV2) were prescribed to primary and nodal target volumes.
      Clinical planning objectives were achieved by both the optimization techniques.
      Dosimetric parameters were calculated for PTVs, and quantitative analyses were
      performed for critical organs. Monitor units were compared between two TPSs, and
      gamma analysis was performed between I'matriXX measured and TPS calculated.
      RESULTS: Clinically, acceptable VMAT plans showed comparable dose distributions
      between TPSB and TPSP optimization techniques. Comparison of mean dose,
      homogeneity index, and conformity index for PTV1 showed no statistical difference
      (P - 0.922, 0.096, and 0.097); however, in PTV2 statistically significant
      difference was observed (P - 0.024, 0.008, and 0.002) between TPSB and TPSP. TPSB
      optimization showed statistically significant superiority for spinal cord and
      brainstem (D1% P - 0.0078, 0.00002) whereas improved parotid sparing was observed
      in TPSP optimization (mean dose P - 0.00205). Gamma analysis illustrated that
      both systems could produce clinically deliverable plans. CONCLUSION: VMAT plans
      by TPSP and TPSB offered clinically acceptable dose distributions. TPSB-based
      optimization showed enhanced sparing of serial organs whereas TPSP-based
      optimization showed superior sparing of parallel organs.

PMID- 28508846
TI  - Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy
      for uterine and cervical cancer using kilovoltage cone-beam computed tomography
      and its effect on planning target volume margins.
AB  - PURPOSE: To achieve the best possible therapeutic ratio using high-precision
      techniques (image-guided radiation therapy/volumetric modulated arc therapy
      [IGRT/VMAT]) of external beam radiation therapy in cases of carcinoma cervix
      using kilovoltage cone-beam computed tomography (kV-CBCT). MATERIALS AND METHODS:
      One hundred and five patients of gynecological malignancies who were treated with
      IGRT (IGRT/VMAT) were included in the study. CBCT was done once a week for
      intensity-modulated radiation therapy and daily in IGRT/VMAT. These images were
      registered with the planning CT scan images and translational errors were applied
      and recorded. In all, 2078 CBCT images were studied. The margins of planning
      target volume were calculated from the variations in the setup. RESULTS: The
      setup variation was 5.8, 10.3, and 5.6 mm in anteroposterior, superoinferior, and
      mediolateral direction. This allowed adequate dose delivery to the clinical
      target volume and the sparing of organ at risks. CONCLUSION: Daily kV-CBCT is a
      satisfactory method of accurate patient positioning in treating gynecological
      cancers with high-precision techniques. This resulted in avoiding geographic
      miss.

PMID- 28508847
TI  - Role of aquaporins in oral cancer.
AB  - Aquaporins (AQP) are the membrane proteins involved in the transport of water and
      some neutral solutes. Thirteen types of AQP are identified in various human
      tissues. The expression of AQP's has been studied in various tumors among one is
      oral cancer. These molecules are involved in cell proliferation, migration, and
      metastasis. AQP target inhibitors act directly or indirectly through focal
      adhesion kinase-mitogen-activated protein kinase signaling pathway and shown
      promising results along with anti-cancer drugs. However, further researches were
      required to verify the efficiency and safety of these AQPs-target inhibitors in
      clinical therapy.

PMID- 28508848
TI  - Recurrent osteosarcoma with calcified liver metastases: Uncommon development of a
      common disease.
AB  - Osteosarcoma is the commonest primary malignant bone tumor. Since bones lack a
      lymphatic system, metastatic spread in these tumors is exclusively hematogenous,
      the commonest sites being lungs and bone. We report a case of osteosarcoma
      humerus which recurred locally after primary therapy consisting of neoadjuvant
      chemotherapy and limb salvage surgery, who developed calcified liver metastases
      in addition to local and pulmonary relapse. Liver, though a common site of
      hematogenous spread in most solid tumors, has rarely been reported to be involved
      in metastatic osteosarcomas.

PMID- 28508849
TI  - Coexistence of hard palate carcinoma with tuberculosis: A rarity.
AB  - Coexistence of tuberculosis (TB) and palatal malignancy is a rare phenomenon and
      it has never been reported. Here, we present a case of hard palate carcinoma with
      TB in a 60-year-old male patient who was successfully managed by three pronged
      approaches by combining antitubercular therapy with chemotherapy and
      radiotherapy.

PMID- 28508850
TI  - Anaplastic hemangiopericytoma of eyelid: An unusual location.
AB  - Hemangiopericytomas (HPCs) are rare soft tissue tumors. The eyelid is a very
      uncommon site for these tumors, and an anaplastic variant of HPC in the eyelid
      has not been reported before. A 44-year-old male presented with complaints of
      slowly progressive, painless swelling on the inner aspect of the left upper
      eyelid for 9 months. He underwent local excision of the swelling and
      histopathology revealed a WHO Grade III anaplastic HPC. Whole body 18 F
      fluorodeoxyglucose positron emission tomography-computed tomography done
      postoperatively did not show any evidence of local or distant disease. The
      patient was planned for adjuvant radiotherapy of 60 Gy in 30 fractions over 6
      weeks in view of high grade of histopathology and doubtful margins. He is disease
      free at the time of the last follow-up. To the best of our knowledge, this is the
      first case of anaplastic HPC of eyelid being reported in English literature.

PMID- 28508851
TI  - Sialadenoma papilliferum: A rare case report and review of literature.
AB  - Sialadenoma papilliferum (SP) classified under the ductal papillomas by the WHO
      is a rare benign tumor of minor salivary glands. It is a rare lesion of salivary
      glands predominantly affecting the minor glands. It has characteristic exophytic
      and endophytic clinical growth pattern. Histopathologically, it is characterized
      by papillary projections supported by fibrovascular connective tissue core and
      infiltrated with mixed inflammatory cells. The ductal lining epithelium of double
      layered cells of luminal layer of tall columnar cells and a basilar layer of
      small cuboidal cells shows additional papillary projections into the lumen. We
      report a case of SP of mid palate.

PMID- 28508852
TI  - Transcoelomic spread and ovarian seeding during ovulation: A possible
      pathogenesis of Krukenberg tumor.

PMID- 28508853
TI  - Accelerated fraction radiation therapy versus concurrent chemoradiation therapy
      for locally advanced head and neck cancers: Is there evidence of equivalent
      effect?

PMID- 28508854
TI  - Erratum: Effects of food insecurity on the women esophageal cancer in the Zanjan
      Province.
AB  - This corrects the article DOI: 10.4103/0973-1482.206303.].

PMID- 28508855
TI  - Retraction: Evaluation and identification of factors related to KRAS and BRAF
      gene mutations in colorectal cancer: A meta analysis.
AB  - [This corrects the article DOI: 10.4103/0973-1482.206304.].

PMID- 28508856
TI  - Association between carotid plaque score and microvascular complications of type
      2 diabetes.
AB  - INTRODUCTION: According to the "common soil" hypothesis, diabetic microangiopathy
      and macroangiopathy have a similar pathophysiological background. It has been
      well documented that carotid artery atherosclerosis in patients with type 2
      diabetes is associated with cardiovascular complications; however, it remains
      unclear whether there is a similar association for microvascular complications.
      OBJECTIVES: We investigated whether the carotid plaque score and the carotid
      intima-media thickness (IMT) are associated with macroangiopathic and
      microangiopathic complications of type 2 diabetes. PATIENTS AND METHODS: We
      enrolled patients with type 2 diabetes and microvascular complications or overt
      macroangiopathy. A B-mode carotid ultrasound was performed in all participants,
      and anthropometric parameters, hemoglobin A1c (HbA1c) levels, lipid profile, and
      smoking status were assessed. RESULTS: The study included 73 patients (mean [SD]
      age, 63.6 [7.5] years; 36 men [49%]). The mean (SD) diabetes duration was 11.7
      (8.1) years. Microvascular complications were observed in 32 patients (43.8%),
      and overt macroangiopathy, in 42 (57.5%). Hypertension was reported for 60
      patients (82%); dyslipidemia, for 56 (77%); obesity, for 37 (51%); and smoking,
      for 10 (14%). A multivariate regression analysis showed that the carotid plaque
      score, but not carotid IMT, was significantly associated with dyslipidemia (P =
      0.03) and microangiopathy (P = 0.01). CONCLUSIONS: Our results indicate that,
      unlike carotid IMT, the carotid plaque score is independently associated with
      microangiopathic complications in type 2 diabetes. Patients with a high plaque
      score should receive special care and the most intensive treatment to stop
      progression of these complications.

PMID- 28508857
TI  - Controlling photophysical properties of ultrasmall conjugated polymer
      nanoparticles through polymer chain packing.
AB  - Applications of conjugated polymer nanoparticles (Pdots) for imaging and sensing
      depend on their size, fluorescence brightness and intraparticle energy transfer.
      The molecular design of conjugated polymers (CPs) has been the main focus of the
      development of Pdots. Here we demonstrate that proper control of the physical
      interactions between the chains is as critical as the molecular design. The
      unique design of twisted CPs and fine-tuning of the reprecipitation conditions
      allow us to fabricate ultrasmall (3.0-4.5 nm) Pdots with excellent
      photostability. Extensive photophysical and structural characterization reveals
      the essential role played by the packing of the polymer chains in the particles
      in the intraparticle spatial alignment of the emitting sites, which regulate the
      fluorescence brightness and the intraparticle energy migration efficiency. Our
      findings enhance understanding of the relationship between chain interactions and
      the photophysical properties of CP nanomaterials, providing a framework for
      designing and fabricating functional Pdots for imaging applications.

PMID- 28508858
TI  - Onset of meso-scale turbulence in active nematics.
AB  - Meso-scale turbulence is an innate phenomenon, distinct from inertial turbulence,
      that spontaneously occurs at low Reynolds number in fluidized biological systems.
      This spatiotemporal disordered flow radically changes nutrient and molecular
      transport in living fluids and can strongly affect the collective behaviour in
      prominent biological processes, including biofilm formation, morphogenesis and
      cancer invasion. Despite its crucial role in such physiological processes,
      understanding meso-scale turbulence and any relation to classical inertial
      turbulence remains obscure. Here we show how the motion of active matter along a
      micro-channel transitions to meso-scale turbulence through the evolution of
      locally disordered patches (active puffs) from an ordered vortex-lattice flow
      state. We demonstrate that the stationary critical exponents of this transition
      to meso-scale turbulence in a channel coincide with the directed percolation
      universality class. This finding bridges our understanding of the onset of low
      Reynolds-number meso-scale turbulence and traditional scale-invariant turbulence
      in confinement.

PMID- 28508860
TI  - Circular RNAs: Coding or noncoding?
AB  - Circular RNAs (circRNAs) were only recently discovered as a new class of
      noncoding RNAs, functionally still largely uncharacterized. Three publications
      that appeared concurrently in Cell Research and Molecular Cell provide initial
      evidence for certain endogenous circRNAs coding for proteins.

PMID- 28508861
TI  - Erratum: Biotemplating pores with size and shape diversity for Li-oxygen Battery
      Cathodes.

PMID- 28508859
TI  - Plastic roles of pericytes in the blood-retinal barrier.
AB  - The blood-retinal barrier (BRB) consists of tightly interconnected capillary
      endothelial cells covered with pericytes and glia, but the role of the pericytes
      in BRB regulation is not fully understood. Here, we show that platelet-derived
      growth factor (PDGF)-B/PDGF receptor beta (PDGFRbeta) signalling is critical in
      formation and maturation of BRB through active recruitment of pericytes onto
      growing retinal vessels. Impaired pericyte recruitment to the vessels shows
      multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption.
      However, PDGF-B/PDGFRbeta signalling is expendable for maintaining BRB integrity
      in adult mice. Although selective pericyte loss in stable adult retinal vessels
      surprisingly does not cause BRB disintegration, it sensitizes retinal vascular
      endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2
      (Ang2) in ECs through FOXO1 activation and triggering a positive feedback that
      resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating
      Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic
      approaches to reduce retinal damages upon DR progression.

PMID- 28508862
TI  - Nanogenerator-based dual-functional and self-powered thin patch loudspeaker or
      microphone for flexible electronics.
AB  - Ferroelectret nanogenerators were recently introduced as a promising alternative
      technology for harvesting kinetic energy. Here we report the device's intrinsic
      properties that allow for the bidirectional conversion of energy between
      electrical and mechanical domains; thus extending its potential use in wearable
      electronics beyond the power generation realm. This electromechanical coupling,
      combined with their flexibility and thin film-like form, bestows dual-functional
      transducing capabilities to the device that are used in this work to demonstrate
      its use as a thin, wearable and self-powered loudspeaker or microphone patch. To
      determine the device's performance and applicability, sound pressure level is
      characterized in both space and frequency domains for three different
      configurations. The confirmed device's high performance is further validated
      through its integration in three different systems: a music-playing flag, a sound
      recording film and a flexible microphone for security applications.

PMID- 28508863
TI  - Anthropogenic iron oxide aerosols enhance atmospheric heating.
AB  - Combustion-induced carbonaceous aerosols, particularly black carbon (BC) and
      brown carbon (BrC), have been largely considered as the only significant
      anthropogenic contributors to shortwave atmospheric heating. Natural iron oxide
      (FeOx) has been recognized as an important contributor, but the potential
      contribution of anthropogenic FeOx is unknown. In this study, we quantify the
      abundance of FeOx over East Asia through aircraft measurements using a modified
      single-particle soot photometer. The majority of airborne FeOx particles in the
      continental outflows are of anthropogenic origin in the form of aggregated
      magnetite nanoparticles. The shortwave absorbing powers (Pabs) attributable to
      FeOx and to BC are calculated on the basis of their size-resolved mass
      concentrations and the mean Pabs(FeOx)/Pabs(BC) ratio in the continental outflows
      is estimated to be at least 4-7%. We demonstrate that in addition to carbonaceous
      aerosols the aggregate of magnetite nanoparticles is a significant anthropogenic
      contributor to shortwave atmospheric heating.

PMID- 28508864
TI  - Power generator driven by Maxwell's demon.
AB  - Maxwell's demon is an imaginary entity that reduces the entropy of a system and
      generates free energy in the system. About 150 years after its proposal,
      theoretical studies explained the physical validity of Maxwell's demon in the
      context of information thermodynamics, and there have been successful
      experimental demonstrations of energy generation by the demon. The demon's next
      task is to convert the generated free energy to work that acts on the
      surroundings. Here, we demonstrate that Maxwell's demon can generate and output
      electric current and power with individual randomly moving electrons in small
      transistors. Real-time monitoring of electron motion shows that two transistors
      functioning as gates that control an electron's trajectory so that an electron
      moves directionally. A numerical calculation reveals that power generation is
      increased by miniaturizing the room in which the electrons are partitioned. These
      results suggest that evolving transistor-miniaturization technology can increase
      the demon's power output.

PMID- 28508866
TI  - Tuning colloidal quantum dot band edge positions through solution-phase surface
      chemistry modification.
AB  - Band edge positions of semiconductors determine their functionality in many
      optoelectronic applications such as photovoltaics, photoelectrochemical cells and
      light emitting diodes. Here we show that band edge positions of lead sulfide
      (PbS) colloidal semiconductor nanocrystals, specifically quantum dots (QDs), can
      be tuned over 2.0 eV through surface chemistry modification. We achieved this
      remarkable control through the development of simple, robust and scalable
      solution-phase ligand exchange methods, which completely replace native ligands
      with functionalized cinnamate ligands, allowing for well-defined, highly tunable
      chemical systems. By combining experiments and ab initio simulations, we
      establish clear relationships between QD surface chemistry and the band edge
      positions of ligand/QD hybrid systems. We find that in addition to ligand dipole,
      inter-QD ligand shell inter-digitization contributes to the band edge shifts. We
      expect that our established relationships and principles can help guide future
      optimization of functional organic/inorganic hybrid nanostructures for diverse
      optoelectronic applications.

PMID- 28508865
TI  - An allosteric site in the T-cell receptor Cbeta domain plays a critical
      signalling role.
AB  - The molecular mechanism through which the interaction of a clonotypic alphabeta T
      cell receptor (TCR) with a peptide-loaded major histocompatibility complex
      (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a
      high-affinity TCR (B4.2.3) to examine the structural changes that accompany
      binding to its p/MHC ligand (P18-I10/H2-Dd). In addition to conformational
      changes in complementarity-determining regions (CDRs) of the TCR seen in
      comparison of unliganded and bound X-ray structures, NMR characterization of the
      TCR beta-chain dynamics reveals significant chemical shift effects in sites
      removed from the MHC-binding site. Remodelling of electrostatic interactions near
      the Cbeta H3 helix at the membrane-proximal face of the TCR, a region implicated
      in interactions with the CD3 co-receptor, suggests a possible role for an
      allosteric mechanism in TCR signalling. The contribution of these TCR residues to
      signal transduction is supported by mutagenesis and T-cell functional assays.

PMID- 28508869
TI  - Multidisciplinary Team-Based Approaches to IBD Management: How Might "One-Stop
      Shopping" Work for Complex IBD Care?

PMID- 28508867
TI  - Bloating and Abdominal Distension: Old Misconceptions and Current Knowledge.
AB  - Bloating, as a symptom and abdominal distension, as a sign, are both common
      functional-type complaints and challenging to manage effectively. Individual
      patients may weight differently the impact of bloating and distension on their
      well-being. Complaints may range from chronic highly distressing pain to simply
      annoying and unfashionable protrusion of the abdomen. To avoid mishaps, organic
      bloating, and distension should always be considered first and appropriated
      assessed. Functional bloating and distension often present in association with
      other manifestations of irritable bowel syndrome or functional dyspepsia and in
      that context patients tend to regard them as most troublesome. A mechanism-based
      management bloating and distension should be ideal but elucidating key
      operational mechanisms in individual patients is not always feasible. Some clues
      may be gathered through a detailed dietary history, by assessing bowel movement
      frequency and stool consistency and special imaging technique to measure
      abdominal shape during episodes of distension. In severe, protracted cases it may
      be appropriate to refer the patient to a specialized center where motility,
      visceral sensitivity, and abdominal muscle activity in response to intraluminal
      stimuli may be measured. Therapeutic resources focussed upon presumed or
      demonstrated pathogenetic mechanism include dietary modification, microbiome
      modulation, promoting gas evacuation, attenuating visceral perception, and
      controlling abdominal wall muscle activity via biofeedback.

PMID- 28508868
TI  - Influence of Age and Eosinophilic Esophagitis on Esophageal Distensibility in a
      Pediatric Cohort.
AB  - OBJECTIVES: Sequelae of eosinophilic esophagitis (EoE) include food impaction and
      esophageal stricture. Duration of inflammation is a predicted risk factor;
      however, complications remain unpredictable. Studies using the functional lumen
      imaging probe (FLIP) have demonstrated decreased distensibility of the esophagus
      in adult patients with EoE. As the impact of inflammation on the developing
      esophagus is unknown, we investigated esophageal distensibility in a pediatric
      cohort to determine the effect of age, ongoing inflammation, and fibrotic
      features on distensibility. METHODS: We conducted a prospective observational
      study at two tertiary pediatric institutions. Subjects underwent FLIP evaluation
      during endoscopy to determine distensibility of the esophagus. During stepwise
      distension, simultaneous intrabag pressure and 16 channels of cross-sectional
      areas were measured. The minimal diameter at maximal esophageal distention at an
      intrabag pressure of 40 mm Hg was identified. Distensibility was compared between
      EoE and non-EoE subjects and between clinical variables within the EoE cohort.
      Potential confounding variables were identified. RESULTS: Forty-four non-EoE and
      88 EoE subjects aged 3-18 years were evaluated. Age positively correlated with
      esophageal distensibility in the non-EoE cohort, but this trend was not observed
      in the EoE population. Subjects with EoE had reduced distensibility even after
      adjusting for age. Active inflammation (eosinophils >15 eos/high-power field),
      histological lamina propria fibrosis, and various features of a fibrotic
      phenotype (stricture, food impaction, circumferential rings on endoscopy) were
      associated with decreased distensibility within the EoE cohort. FLIP was safe,
      feasible, and well tolerated. CONCLUSIONS: These findings suggest that remodeling
      occurs in the pediatric EoE population, warranting early diagnosis and initiation
      of therapy prior to the onset of disease complications.

PMID- 28508870
TI  - Injection and controlled motion of conducting domain walls in improper
      ferroelectric Cu-Cl boracite.
AB  - Ferroelectric domain walls constitute a completely new class of sheet-like
      functional material. Moreover, since domain walls are generally writable,
      erasable and mobile, they could be useful in functionally agile devices: for
      example, creating and moving conducting walls could make or break electrical
      connections in new forms of reconfigurable nanocircuitry. However, significant
      challenges exist: site-specific injection and annihilation of planar walls, which
      show robust conductivity, has not been easy to achieve. Here, we report the
      observation, mechanical writing and controlled movement of charged conducting
      domain walls in the improper-ferroelectric Cu3B7O13Cl. Walls are straight, tens
      of microns long and exist as a consequence of elastic compatibility conditions
      between specific domain pairs. We show that site-specific injection of conducting
      walls of up to hundreds of microns in length can be achieved through locally
      applied point-stress and, once created, that they can be moved and repositioned
      using applied electric fields.

PMID- 28508871
TI  - Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven
      hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is the second
      leading cause of cancer mortality worldwide. Fibroblast Growth Factor 19 (FGF19)
      is one of the most frequently amplified genes in HCC patients. Moreover, mice
      expressing an FGF19 transgene have been shown to develop HCC. However, the
      downstream signalling pathways that mediate FGF19-dependent tumorigenesis remain
      to be deciphered. Here we show that FGF19 triggers a previously unsuspected, non
      cell-autonomous program to activate STAT3 signalling in hepatocytes through IL-6
      produced in the liver microenvironment. We show that the hepatocyte-specific
      deletion of Stat3, genetic ablation of Il6, treatment with a neutralizing anti-IL
      6 antibody or administration of a small-molecule JAK inhibitor, abolishes FGF19
      induced tumorigenesis, while the regulatory functions of FGF19 in bile acid,
      glucose and energy metabolism remain intact. Collectively, these data reveal a
      key role for the IL-6/STAT3 axis in potentiating FGF19-driven HCC in mice, a
      finding which may have translational relevance in HCC pathogenesis.

PMID- 28508874
TI  - Lung cancer: Tracing tumour evolution.

PMID- 28508872
TI  - Actin stress fiber organization promotes cell stiffening and proliferation of pre
      invasive breast cancer cells.
AB  - Studies of the role of actin in tumour progression have highlighted its key
      contribution in cell softening associated with cell invasion. Here, using a human
      breast cell line with conditional Src induction, we demonstrate that cells
      undergo a stiffening state prior to acquiring malignant features. This state is
      characterized by the transient accumulation of stress fibres and upregulation of
      Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient
      cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src
      activation and progression towards a fully transformed state. Accordingly, EVL
      accumulates predominantly in premalignant breast lesions and is required for Src
      induced epithelial overgrowth in Drosophila. While cell softening allows for
      cancer cell invasion, our work reveals that stress fibre-mediated cell stiffening
      could drive tumour growth during premalignant stages. A careful consideration of
      the mechanical properties of tumour cells could therefore offer new avenues of
      exploration when designing cancer-targeting therapies.

PMID- 28508876
TI  - Post-supereruption recovery at Toba Caldera.
AB  - Large calderas, or supervolcanoes, are sites of the most catastrophic and
      hazardous events on Earth, yet the temporal details of post-supereruption
      activity, or resurgence, remain largely unknown, limiting our ability to
      understand how supervolcanoes work and address their hazards. Toba Caldera,
      Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr,
      climactically erupting ~74 ka. Since the supereruption, Toba has been in a state
      of resurgence but its magmatic and uplift history has remained unclear. Here we
      reveal that new 14C, zircon U-Th crystallization and (U-Th)/He ages show
      resurgence commenced at 69.7+/-4.5 ka and continued until at least ~2.7 ka,
      progressing westward across the caldera, as reflected by post-caldera effusive
      lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba,
      Sinabung, shows strong geochemical kinship with Toba, and zircons from recent
      eruption products suggest Toba's climactic magma reservoir extends beneath
      Sinabung and is being tapped during eruptions.

PMID- 28508875
TI  - Early phase clinical trials of anticancer agents in children and adolescents - an
      ITCC perspective.
AB  - In the past decade, the landscape of drug development in oncology has evolved
      dramatically; however, this paradigm shift remains to be adopted in early phase
      clinical trial designs for studies of molecularly targeted agents and
      immunotherapeutic agents in paediatric malignancies. In drug development,
      prioritization of drugs on the basis of knowledge of tumour biology, molecular
      'drivers' of disease and a drug's mechanism of action, and therapeutic unmet
      needs are key elements; these aspects are relevant to early phase paediatric
      trials, in which molecular profiling is strongly encouraged. Herein, we describe
      the strategy of the Innovative Therapies for Children with Cancer (ITCC)
      Consortium, which advocates for the adoption of trial designs that enable
      uninterrupted patient recruitment, the extrapolation from studies in adults when
      possible, and the inclusion of expansion cohorts. If a drug has neither serious
      dose-related toxicities nor a narrow therapeutic index, then studies should
      generally be started at the adult recommended phase II dose corrected for body
      surface area, and act as dose-confirmation studies. The use of adaptive trial
      designs will enable drugs with promising activity to progress rapidly to
      randomized studies and, therefore, will substantially accelerate drug development
      for children and adolescents with cancer.

PMID- 28508873
TI  - Mutant KRAS promotes malignant pleural effusion formation.
AB  - Malignant pleural effusion (MPE) is the lethal consequence of various human
      cancers metastatic to the pleural cavity. However, the mechanisms responsible for
      the development of MPE are still obscure. Here we show that mutant KRAS is
      important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing
      tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into
      the bloodstream to mobilize myeloid cells from the host bone marrow to the
      pleural space via the spleen. These cells promote MPE formation, as indicated by
      splenectomy and splenocyte restoration experiments. In addition, KRAS mutations
      are frequently detected in human MPE and cell lines isolated thereof, but are
      often lost during automated analyses, as indicated by manual versus automated
      examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor
      deltarasin and a monoclonal antibody directed against CCL2 are equally effective
      against an experimental mouse model of MPE, a result that holds promise for
      future efficient therapies against the human condition.

PMID- 28508878
TI  - Incontinence: The dilemma with comparing efficacy of OAB treatments.

PMID- 28508880
TI  - Prostate cancer: 'The prostate' in patients with metastatic prostate cancer: to
      treat or not to treat?

PMID- 28508881
TI  - Prostate cancer: Circulating free DNA as biomarker.

PMID- 28508877
TI  - An overview of female-to-male gender-confirming surgery.
AB  - Gender dysphoria is estimated to occur in approximately 25 million people
      worldwide, and can have severe psychosocial sequelae. Medical and surgical gender
      transition can substantially improve quality-of-life outcomes for individuals
      with gender dysphoria. Individuals seeking to undergo female-to-male (FtM)
      transition have various surgical options available for gender confirmation,
      including facial and chest masculinization, body contouring, and genital surgery.
      The World Professional Association for Transgender Health guidelines should be
      met before the patient undergoes surgery, to ensure that gender-confirming
      surgery is appropriate and indicated. Chest masculinization and metoidioplasty or
      phalloplasty are the most common procedures pursued, and both generally result in
      high levels of patient satisfaction. Phalloplasty, with a resultant aesthetic and
      sensate phallus along with implantable prosthetic, can take upwards of a year to
      accomplish, and is associated with a considerable risk of complications. Urethral
      complications are most frequent, and can be addressed with revision procedures. A
      number of scaffolds, implants, and prostheses are now in development to improve
      outcomes in FtM patients.

PMID- 28508883
TI  - Corrigendum: Investigating starch gelatinization through Stokes vector resolved
      second harmonic generation microscopy.

PMID- 28508882
TI  - Voltage-controlled interlayer coupling in perpendicularly magnetized magnetic
      tunnel junctions.
AB  - Magnetic interlayer coupling is one of the central phenomena in spintronics. It
      has been predicted that the sign of interlayer coupling can be manipulated by
      electric fields, instead of electric currents, thereby offering a promising low
      energy magnetization switching mechanism. Here we present the experimental
      demonstration of voltage-controlled interlayer coupling in a new perpendicular
      magnetic tunnel junction system with a GdOx tunnel barrier, where a large
      perpendicular magnetic anisotropy and a sizable tunnelling magnetoresistance have
      been achieved at room temperature. Owing to the interfacial nature of the
      magnetism, the ability to move oxygen vacancies within the barrier, and a large
      proximity-induced magnetization of GdOx, both the magnitude and the sign of the
      interlayer coupling in these junctions can be directly controlled by voltage.
      These results pave a new path towards achieving energy-efficient magnetization
      switching by controlling interlayer coupling.

PMID- 28508884
TI  - A hybrid cloud read aligner based on MinHash and kmer voting that preserves
      privacy.
AB  - Low-cost clouds can alleviate the compute and storage burden of the genome
      sequencing data explosion. However, moving personal genome data analysis to the
      cloud can raise serious privacy concerns. Here, we devise a method named Balaur,
      a privacy preserving read mapper for hybrid clouds based on locality sensitive
      hashing and kmer voting. Balaur can securely outsource a substantial fraction of
      the computation to the public cloud, while being highly competitive in accuracy
      and speed with non-private state-of-the-art read aligners on short read data. We
      also show that the method is significantly faster than the state of the art in
      long read mapping. Therefore, Balaur can enable institutions handling massive
      genomic data sets to shift part of their analysis to the cloud without
      sacrificing accuracy or exposing sensitive information to an untrusted third
      party.

PMID- 28508879
TI  - Oxidative stress and male infertility.
AB  - DNA damage, largely owing to oxidative stress, is a leading cause of defective
      sperm function. High levels of oxidative stress result in damage to sperm DNA,
      RNA transcripts, and telomeres and, therefore might provide a common underlying
      aetiology of male infertility and recurrent pregnancy loss, in addition to
      congenital malformations, complex neuropsychiatric disorders, and childhood
      cancers in children fathered by men with defective sperm cells. Spermatozoa are
      highly vulnerable to oxidative stress owing to limited levels of antioxidant
      defence and a single, limited DNA-damage detection and repair mechanism.
      Oxidative stress is predominantly caused by a host of lifestyle-related factors,
      the majority of which are modifiable. Antioxidant regimens and lifestyle
      modifications could both be plausible therapeutic approaches that enable the
      burden of oxidative-stress-induced male factor infertility to be overcome.
      Lifestyle interventions including yoga and meditation can substantially improve
      the integrity of sperm DNA by reducing levels of oxidative DNA damage, regulating
      oxidative stress and by increasing the expression of genes responsible for DNA
      repair, cell-cycle control and anti-inflammatory effects. Oxidative stress is
      caused by various modifiable factors, and the use of simple interventions can
      decrease levels of oxidative stress, and therefore reduce the incidence of both
      infertility and complex diseases in the resultant offspring.

PMID- 28508885
TI  - First Characterisation of Volatile Organic Compounds Emitted by Banana Plants.
AB  - Banana (Musa sp.) ranks fourth in term of worldwide fruit production, and has
      economical and nutritional key values. The Cavendish cultivars correspond to more
      than 90% of the production of dessert banana while cooking cultivars are widely
      consumed locally around the banana belt production area. Many plants, if not all,
      produce Volatile Organic Compounds (VOCs) as a means of communication with their
      environment. Although flower and fruit VOCs have been studied for banana, the
      VOCs produced by the plant have never been identified despite their importance in
      plant health and development. A volatile collection methodology was optimized to
      improve the sensitivity and reproducibility of VOCs analysis from banana plants.
      We have identified 11 VOCs for the Cavendish, mainly (E,E)-alpha-farnesene (87.90
      +/- 11.28 ng/MUl), methyl salicylate (33.82 +/- 14.29) and 6-methyl-5-hepten-2
      one (29.60 +/- 11.66), and 14 VOCs for the Pacific Plantain cultivar, mainly
      (Z,E)-alpha-farnesene (799.64 +/- 503.15), (E,E)-alpha-farnesene (571.24 +/-
      381.70) and (E) beta ocimene (241.76 +/- 158.49). This exploratory study paves
      the way for an in-depth characterisation of VOCs emitted by Musa plants.

PMID- 28508886
TI  - Protein-protein interactions and metabolite channelling in the plant
      tricarboxylic acid cycle.
AB  - Protein complexes of sequential metabolic enzymes, often termed metabolons, may
      permit direct channelling of metabolites between the enzymes, providing increased
      control over metabolic pathway fluxes. Experimental evidence supporting their
      existence in vivo remains fragmentary. In the present study, we test binary
      interactions of the proteins constituting the plant tricarboxylic acid (TCA)
      cycle. We integrate (semi-)quantitative results from affinity purification-mass
      spectrometry, split-luciferase and yeast-two-hybrid assays to generate a single
      reliability score for assessing protein-protein interactions. By this approach,
      we identify 158 interactions including those between catalytic subunits of
      sequential enzymes and between subunits of enzymes mediating non-adjacent
      reactions. We reveal channelling of citrate and fumarate in isolated potato
      mitochondria by isotope dilution experiments. These results provide evidence for
      a functional TCA cycle metabolon in plants, which we discuss in the context of
      contemporary understanding of this pathway in other kingdoms.

PMID- 28508888
TI  - Association among practice frequency on depression and stress among competitive
      US male wheelchair rugby athletes with tetraplegia.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine whether frequency of
      training is related to self-reported lower psychological distress, defined as
      depressive symptomology and perceived stress, among the US male wheelchair rugby
      athletes with tetraplegia. SETTING: United States. METHODS: Survey data were
      collected on a convenience sample at wheelchair rugby tournaments from January
      April 2016. Participants self-reported depressive symptomology (CES-D-10),
      perceived stress scale (PSS), and frequency of rugby practice. Covariate-adjusted
      regression models were conducted among the full sample and a subsample of
      individuals who reported spinal cord injury (SCI) as the nature of their
      disability. RESULTS: Participants included 150 males with tetraplegia, and 87%
      identified the nature of their disability as SCI. Participants were primarily
      Caucasian with an average age of ~35 years. Participants scored low on measures
      of depressive symptomology (mean=5.63; s.d.=4.35) and perceived stress
      (mean=4.63; s.d.=2.73). Sixty-seven percent of the participants practiced two or
      more times per week. Results of the main analyses indicated that practicing
      wheelchair rugby two times or more (compared to once a week or less) was
      significantly associated with lower depressive symptomology and perceived stress
      among the full sample and subsample of individuals with SCI. CONCLUSIONS: Greater
      frequency of wheelchair rugby participation was associated with lower levels of
      psychological distress. Future research should examine the directional and
      mechanistic relationship between frequency of sports participation and
      psychological distress to inform the benefits of adaptive sport.

PMID- 28508887
TI  - An evolutionary switch in ND2 enables Src kinase regulation of NMDA receptors.
AB  - The non-receptor tyrosine kinase Src is a key signalling hub for upregulating the
      function of N-methyl D-aspartate receptors (NMDARs). Src is anchored within the
      NMDAR complex via NADH dehydrogenase subunit 2 (ND2), a mitochondrially encoded
      adaptor protein. The interacting regions between Src and ND2 have been broadly
      identified, but the interaction between ND2 and the NMDAR has remained elusive.
      Here we generate a homology model of ND2 and dock it onto the NMDAR via the
      transmembrane domain of GluN1. This interaction is enabled by the evolutionary
      loss of three helices in bilaterian ND2 proteins compared to their ancestral
      homologues. We experimentally validate our model and demonstrate that blocking
      this interaction with an ND2 fragment identified in our experimental studies
      prevents Src-mediated upregulation of NMDAR currents in neurons. Our findings
      establish the mode of interaction between an NMDAR accessory protein with one of
      the core subunits of the receptor.

PMID- 28508889
TI  - Influence of bladder lithiasis on lower urinary tract dynamics in patients with
      spinal cord injury.
AB  - STUDY DESIGN: A prospective and a case-matched control study. OBJECTIVES: To
      study the lower urinary tract dysfunction associated with bladder lithiasis in
      patients with spinal cord injury (SCI). SETTING: Toledo (Spain). METHODS: We have
      carried out a urodynamic study in 30 patients with SCI with lithiasis in their
      bladder before and 3 months after bladder endoscopic lithotripsy. This second
      study was compared with the urodynamic findings of a different group of 30
      patients with SCI, without a history of bladder lithiasis, paired with cases by
      gender and date of urodynamic study. RESULTS: We have found that the prevalence
      of neurogenic detrusor overactivity (NDO) was significantly different after
      bladder lithotripsy, although the cystomanometric capacity was significantly
      increased. A group of patients with lithiasis showed a maximum flow rate, a
      voiding maximum detrusor pressure and the detrusor contractility parameter Wmax
      lower than that in controls. On the other hand, a voiding abdominal straining was
      found to be significantly greater than that in controls. CONCLUSIONS: Bladder
      lithiasis affects the presence of NDO in patients with SCI. Patients with SCI who
      develop bladder lithiasis present a lower detrusor contractility power compared
      with those who do not.

PMID- 28508890
TI  - Attentional requirements of postural control in people with spinal cord injury:
      the effect of dual task.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To investigate the attentional
      requirements for maintaining standing balance in people with spinal cord injury
      (SCI) using a dual-task paradigm and to compare standing balance performance
      between SCI and able-bodied (AB) controls. SETTING: LaboratoryMethods:Nine adults
      with incomplete SCI, who were able to stand unassisted were recruited, along with
      eight AB controls. Subjects performed a dual task involving counting backwards by
      3 s out loud while standing with eyes open or closed. The primary outcome
      measures were the differences between SCI and control groups for movement
      reinvestment and the change in performance between single task and dual task for:
      (i) maximum standing time (STime); (ii) error ratio and total number of words
      uttered; and (iii) center of pressure measures. Perceptual measures included
      perceived mental workload, fear and confidence. RESULTS: SCI subjects stood for
      shorter duration during dual task (stand and count) than single task (stand)
      compared with controls during eyes closed. Significant differences between groups
      were observed for movement reinvestment, center of pressure, perceived mental
      effort, fear and confidence. No significant effects were observed for math-task
      performance. CONCLUSIONS: Total STime during eyes closed is adversely affected by
      the addition of a math task for SCI subjects. Perceptual measures appear to
      correspond to increases in postural sway and conscious control of standing in
      subjects with SCI. Individuals who can stand for >60 s with eyes closed do not
      appear to be significantly affected by the addition of a concurrent secondary
      task of minimal mental workload.

PMID- 28508891
TI  - Joint morphogenetic cells in the adult mammalian synovium.
AB  - The stem cells that safeguard synovial joints in adulthood are undefined. Studies
      on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here
      we show that lineage tracing of Gdf5-expressing joint interzone cells identifies
      in adult mouse synovium an MSC population largely negative for the skeletal stem
      cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage
      injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation,
      are recruited to a Nestin-GFPhigh perivascular population, and contribute to
      cartilage repair. The transcriptional co-factor Yap is upregulated after injury,
      and its conditional ablation in Gdf5-lineage cells prevents synovial lining
      hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair.
      Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes
      and are able to self-organize three-dimensionally to form a synovial lining-like
      layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic
      properties by patterning a joint-like organ in vivo. Our findings further the
      understanding of the skeletal stem/progenitor cells in adult life.

PMID- 28508892
TI  - High precision hyperfine measurements in Bismuth challenge bound-state strong
      field QED.
AB  - Electrons bound in highly charged heavy ions such as hydrogen-like bismuth
      209Bi82+ experience electromagnetic fields that are a million times stronger than
      in light atoms. Measuring the wavelength of light emitted and absorbed by these
      ions is therefore a sensitive testing ground for quantum electrodynamical (QED)
      effects and especially the electron-nucleus interaction under such extreme
      conditions. However, insufficient knowledge of the nuclear structure has
      prevented a rigorous test of strong-field QED. Here we present a measurement of
      the so-called specific difference between the hyperfine splittings in hydrogen
      like and lithium-like bismuth 209Bi82+,80+ with a precision that is improved by
      more than an order of magnitude. Even though this quantity is believed to be
      largely insensitive to nuclear structure and therefore the most decisive test of
      QED in the strong magnetic field regime, we find a 7-sigma discrepancy compared
      with the theoretical prediction.

PMID- 28508893
TI  - South-American plate advance and forced Andean trench retreat as drivers for
      transient flat subduction episodes.
AB  - At two trench segments below the Andes, the Nazca Plate is subducting sub
      horizontally over ~200-300 km, thought to result from a combination of buoyant
      oceanic-plateau subduction and hydrodynamic mantle-wedge suction. Whether the
      actual conditions for both processes to work in concert existed is uncertain.
      Here we infer from a tectonic reconstruction of the Andes constructed in a mantle
      reference frame that the Nazca slab has retreated at ~2 cm per year since ~50 Ma.
      In the flat slab portions, no rollback has occurred since their formation at ~12
      Ma, generating 'horse-shoe' slab geometries. We propose that, in concert with
      other drivers, an overpressured sub-slab mantle supporting the weight of the slab
      in an advancing upper plate-motion setting can locally impede rollback and
      maintain flat slabs until slab tearing releases the overpressure. Tear subduction
      re-establishes a continuous slab and allows the process to recur, providing a
      mechanism for the transient character of flat slabs.

PMID- 28508894
TI  - Factoring in CD4 T cells during treatment of HIV.

PMID- 28508895
TI  - Exosomes maintain cellular homeostasis by excreting harmful DNA from cells.
AB  - Emerging evidence is revealing that exosomes contribute to many aspects of
      physiology and disease through intercellular communication. However, the
      biological roles of exosome secretion in exosome-secreting cells have remained
      largely unexplored. Here we show that exosome secretion plays a crucial role in
      maintaining cellular homeostasis in exosome-secreting cells. The inhibition of
      exosome secretion results in the accumulation of nuclear DNA in the cytoplasm,
      thereby causing the activation of cytoplasmic DNA sensing machinery. This event
      provokes the innate immune response, leading to reactive oxygen species (ROS)
      dependent DNA damage response and thus induce senescence-like cell-cycle arrest
      or apoptosis in normal human cells. These results, in conjunction with
      observations that exosomes contain various lengths of chromosomal DNA fragments,
      indicate that exosome secretion maintains cellular homeostasis by removing
      harmful cytoplasmic DNA from cells. Together, these findings enhance our
      understanding of exosome biology, and provide valuable new insights into the
      control of cellular homeostasis.

PMID- 28508896
TI  - Obesity-related CpG Methylation (cg07814318) of Kruppel-like Factor-13 (KLF13)
      Gene with Childhood Obesity and its cis-Methylation Quantitative Loci.
AB  - The cg07814318 hypermethylation of Kruppel-like factor 13 (KLF13) gene has been
      reported for its relevancy with Body Mass Index (BMI) from European origin. We
      explored the cg07814318 methylation and its cis-meQTL (cis-methylation
      quantitative loci) of KLF13 from a childhood obesity cohort. The cg07814318
      methylation in blood was significantly associated with obesity and correlated
      with several obesity-related physical and biochemical traits. We examined the
      same loci from purified three human cell types (n = 47), i.e., pre-adipocytes,
      adipocytes and islets. The cg07814318 methylation pattern in pre-adipocytes and
      islets were significant higher in cells from subjects with a higher BMI compared
      with control subjects. By exome sequencing of KLF13 gene in blood with the same
      cohort, we found nine SNPs (single nucleotide polymorphisms) within its gene
      body, and two SNPs (rs11537749 and rs12595641) were as cis-meQTL of cg07814318.
      There was the 2.01% methylation change of cg07814318 between homozygous dominant
      and recessive genotypes, especially, in rs12595641. The sequencing variations
      within KLF13 genes could drive dynamic modifications of obesity-related CpG
      methylation. Differential DNA methylation patterns in the KLF13 gene determined
      from separate blood samples showed that this criterion could be used as a
      surrogate for representing overall epigenetic changes in cells related to
      obesity.

PMID- 28508898
TI  - Dicyanoaurate-based heterobimetallic uranyl coordination polymers.
AB  - The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers and
      molecular complexes has been synthesized. Reactions of [A][Au(CN)2] (A = [nBu4N]+
      or [(Ph3P)2N]+ ([PPN])) and uranyl nitrate in alcoholic solvents in ambient light
      led to [A]2[(UO2)2(MU-eta2:eta2-O2)(NO3)2(MU-Au(CN)2)2], which incorporates
      peroxo ligands into a one-dimensional ladder topology with alternating aurophilic
      and peroxo rungs. Conducting the reaction with non-alcoholic solvents formed two
      polymorphs of a one-dimensional chain, [PPN][UO2(NO3)2Au(CN)2], from acetone, and
      a molecular analogue, [PPN]2[UO2(NO3)2(Au(CN)2)2], from acetonitrile, none of
      which exhibited aurophilic interactions. The addition of 2,2'-bipyridine to the
      initial reaction resulted in [UO2(bipy)(MeO)(MeOH)]2[(MU-Au(CN)2)(Au(CN)2)], a
      one-dimensional structure which propagates via a series of linear aurophilic
      bonds with pendant uranyl complexes; methanol and methoxy ligands provide
      additional connections through hydrogen bonding. The addition of 5,5'-dimethyl
      2,2'-bipyridine using solvothermal conditions resulted in the one-dimensional
      ladder [UO2(Me2bipy)Au(CN)2]2[(MU-OH)2], generated through aurophilic bonds and
      hydroxide ligands. The incorporation of 2,2':6',2''-terpyridine (terpy) using
      solvothermal conditions resulted in [[UO2(terpy)]2(MU-NO3)(MU-O)][Au(CN)2], a
      molecular salt with no aurophilic interactions. Emission spectra attributable to
      aurophilic interactions are observed in [nBu4N]2[(UO2)2(MU-eta2:eta2-O2)(NO3)2(MU
      Au(CN)2)2], while all others only show emission typical of the uranyl cation.

PMID- 28508899
TI  - The quasi-unchanged gas-phase molecular structures of the atmospheric aerosol
      precursor beta-pinene and its oxidation product nopinone.
AB  - The rotational spectra of the two bicyclic molecules beta-pinene and its
      oxidation product nopinone were investigated in the gas phase, using Fourier
      transform microwave spectroscopy coupled to a supersonic jet, in the 2-20 GHz
      range. The parent species and all heavy atom isotopologues have been observed in
      their natural abundance. The spectroscopic parameters of the ground states were
      determined from a Watson's Hamiltonian in the A reduction. The rotational
      constants were used together with geometrical parameters obtained from ab initio
      calculations to determine the r0 and r structures of the skeletons, without any
      structural assumption in the fit concerning the heavy atoms. Comparison with
      solid phase and other bicyclic monoterpenes unveiled an unprecedented complete
      set of geometrical parameters for the rigid cages. The structures of beta-pinene
      and nopinone are very close, except for the substituents at C2. In the gas phase
      C2 is a centre of planarity in both molecules.

PMID- 28508901
TI  - From polyethylene waxes to HDPE using an alpha,alpha'-bis(arylimino)-2,3:5,6
      bis(pentamethylene)pyridyl-chromium(iii) chloride pre-catalyst in ethylene
      polymerisation.
AB  - Five examples of alpha,alpha'-bis(arylimino)-2,3:5,6-bis(pentamethylene)pyridyl
      chromium(iii) chlorides (aryl = 2,6-Me2Ph Cr1, 2,6-Et2Ph Cr2, 2,6-i-Pr2Ph Cr3,
      2,4,6-Me3Ph Cr4, 2,6-Et2-4-MePh Cr5) have been synthesized by the one-pot
      template reaction of alpha,alpha'-dioxo-2,3:5,6-bis(pentamethylene)pyridine,
      CrCl3.6H2O and the corresponding aniline. The molecular structures of Cr1 and Cr4
      reveal distorted octahedral geometries with the N,N,N-ligand adopting a mer
      configuration. On activation with an aluminium alkyl co-catalyst, Cr1-Cr5
      exhibited high catalytic activities in ethylene polymerization and showed
      outstanding thermal stability operating effectively at 80  degrees C with
      activities up to 1.49 * 107 g of PE (mol of Cr)-1 h-1. Significantly, the nature
      of the co-catalyst employed had a dramatic effect on the molecular weight of the
      polymeric material obtained. For example, using diethylaluminium chloride
      (Et2AlCl) in combination with Cr4 gave high density/high molecular weight
      polyethylene with broad molecular weight distributions (30.9-39.3). By contrast,
      using modified methylaluminoxane (MMAO), strictly linear polyethylene waxes of
      lower molecular weight and narrow molecular weight distribution (1.6-2.0) were
      obtained with vinyl end-groups.

PMID- 28508902
TI  - Non-zeolitic properties of the dipeptide l-leucyl-l-leucine as a result of the
      specific nanostructure formation.
AB  - The non-zeolitic behavior of l-leucyl-l-leucine and its self-organization in
      solid state and from solutions with the formation of different nanostructures are
      reported. This dipeptide forms porous crystals, but does not exhibit molecular
      sieve effects typical of classical zeolites and biozeolites. The specific
      sorption properties of l-leucyl-l-leucine result from a change in its crystal
      packing from channel-type to layered-type, when binding strong proton acceptors
      or proton donors of molecular size greater than 18-20 cm3 mol-1. The high
      sorption capacity of l-leucyl-l-leucine toward dichloromethane results from the
      self-organization of the dipeptide, by forming nanofibers or web-like structures.
      The low thermal stability of clathrates of the dipeptide containing large guest
      molecules and the selectivity of l-leucyl-l-leucine toward alcohols over nitriles
      can be used to separate organic mixtures such as methanol/n-butanol and
      methanol/acetonitrile.

PMID- 28508903
TI  - Protonation-modulated localization of excess electrons in histidine aqueous
      solutions revealed by ab initio molecular dynamics simulations: anion-centered
      versus cation-centered localization.
AB  - In this work, we present an ab initio molecular dynamics simulation study on the
      interaction of an excess electron (EE) with histidine in its aqueous solution.
      Two different configurations of histidine (imidazole group protonated or not) are
      considered to reflect its different existing forms in neutral or slightly acidic
      surroundings. The simulation results indicate that localizations of EEs in
      different aqueous histidine solutions are quite different and are strongly
      affected by protonation of the side chain imidazole group and are thus pH
      controlled. In neutral aqueous histidine solution, an EE localizes onto the
      carboxyl anionic group of the amino acid backbone after a relatively lengthy
      diffuse state, performing just like in an aliphatic amino acid solution. But in
      weakly acidic solution in which the side chain imidazole group is protonated, an
      EE undergoes a short lifetime diffuse state and finally localizes on the
      protonated imidazole group. We carefully examine these two different localization
      dynamics processes and analyze the competition between different dominating
      groups in their corresponding electron localization mechanisms. To explain the
      difference, we investigate the frontier molecular orbitals of these two systems
      and find that their energy levels and compositions are important to determine
      these differences. These findings can provide helpful information to understand
      the interaction mechanisms of low energy EEs with amino acids and even
      oligopeptides, especially with aromatic rings.

PMID- 28508905
TI  - An eco-friendly in situ activatable antibiotic via cucurbit[8]uril-mediated
      supramolecular crosslinking of branched polyethylenimine.
AB  - We report an unprecedented, eco-friendly, in situ activatable model antibiotic,
      phenylalanyl-polyethylenimine (PhePEI), to potentially diminish antibiotic
      pollution of the environment and associated antibiotic resistance. The inactive
      PhePEI can be reversibly activated upon supramolecular crosslinking by
      cucurbit[8]uril, conferring potent antibacterial activity.

PMID- 28508904
TI  - Chloride-accelerated Cu-Fenton chemistry for biofilm removal.
AB  - Biofilms present challenges to numerous industries. Herein, a simple approach was
      developed based on chloride-accelerated Fenton chemistry, where copper oxide
      nanoparticles facilitate efficient generation of reactive chlorine species for
      biofilm removal.

PMID- 28508907
TI  - An effective trigger for energy release of vinylheptafulvene-based solar heat
      batteries.
AB  - Stoichiometric copper(i) tetrakis(acetonitrile) is found to activate the thermal
      ring-closure reaction of a series of high-energy vinylheptafulvene isomers to the
      corresponding low-energy and photoactive dihydroazulenes, allowing the release of
      energy upon request.

PMID- 28508897
TI  - Whole genome analysis of a schistosomiasis-transmitting freshwater snail.
AB  - Biomphalaria snails are instrumental in transmission of the human blood fluke
      Schistosoma mansoni. With the World Health Organization's goal to eliminate
      schistosomiasis as a global health problem by 2025, there is now renewed emphasis
      on snail control. Here, we characterize the genome of Biomphalaria glabrata, a
      lophotrochozoan protostome, and provide timely and important information on snail
      biology. We describe aspects of phero-perception, stress responses, immune
      function and regulation of gene expression that support the persistence of B.
      glabrata in the field and may define this species as a suitable snail host for S.
      mansoni. We identify several potential targets for developing novel control
      measures aimed at reducing snail-mediated transmission of schistosomiasis.

PMID- 28508908
TI  - Rapid synthesis of CuInTe2 ultrathin nanoplates with enhanced
      photoelectrochemical properties.
AB  - Ultrathin (2.1 +/- 0.1 nm) single-crystal CuInTe2 two-dimensional (2D) nanoplates
      were synthesized via a rapid colloidal synthesis method. The growth mechanism was
      investigated in detail. Crystal seeds grew via a 2D assembly process of initially
      formed small CuInTe2 nanoparticles followed by recrystallization into single
      crystal nanoplates. The obtained CuInTe2 nanoplates exhibited significantly
      enhanced photoelectrochemical properties compared with the CuInTe2 nanoparticles,
      benefitting from their ultrathin 2D characteristics.

PMID- 28508909
TI  - Pinpointing disulfide connectivities in cysteine-rich proteins.
AB  - A simple MD-based protocol is presented to accurately predict both the sequence
      and order of disulfide bond formation in proteins containing multiple cysteine
      residues. It provides a detailed description of their dynamical and structural
      features, which can be used to perform ensemble-averaged ECD calculations. Plant
      cyclotides are used as model compounds.

PMID- 28508912
TI  - Pyrazine-fused isoindigo: a new building block for polymer solar cells with high
      open circuit voltage.
AB  - Pyrazine-fused isoindigo (PzIIG) was designed and synthesized as a novel electron
      acceptor to construct two D-A conjugated polymers, PzIIG-BDT2TC8 and PzIIG
      BTT2TC10. Both the polymers were successfully applied in polymer solar cells, and
      the PzIIG-BDT2TC8 based solar cell device exhibited a PCE of 5.26% with a high
      Voc over 1.0 V.

PMID- 28508913
TI  - Digitally encoded silica microparticles for multiplexed nucleic acid detection.
AB  - A robust high throughput suspension array was proposed to analyze biomolecules.
      To exploit its capacity for nucleic acid detection, we designed a multiplex
      nested asymmetric PCR (MNAS PCR) that can produce single stranded DNA (ssDNA)
      efficiently without complicated optimization. Multiplexed HPV genotyping was
      demonstrated with high selectivity, high sensitivity and rapid hybridization
      within 20 minutes.

PMID- 28508914
TI  - Photoexcited Ag ejection from a low-temperature He cluster: a simulation study by
      nonadiabatic Ehrenfest ring-polymer molecular dynamics.
AB  - Ring-polymer molecular dynamics (RPMD) simulations have been performed to
      understand the photoexcitation dynamics of an Ag atom embedded in a low
      temperature cluster consisting of 500 helium atoms, after the electronic
      excitation 5p 2P1/2 <- 5p 2S1/2 and 5p 2P3/2 <- 5p 2S1/2 of the Ag atom. Along
      the RPMD trajectory the time evolution of electronic wavefunction within the spin
      orbit 2P manifold is calculated, whereby the time-dependent Schrodinger equation
      and the RPMD equation of motion are coupled, using the a la Ehrenfest mean field
      approach. It is found from the simulations that the Ag atom is ejected from the
      helium cluster with the average time of 100 ps after photoexcitation with the
      average ejection velocity being 60-70 m s-1, which is roughly in line with
      experiment. Meanwhile it is also found that the present simulations do not agree
      with experiment as to the final state of the ejected Ag atom.

PMID- 28508915
TI  - Avoiding the invasion of H2O into Y2Mo3O12 by coating with C3N4 to improve
      negative thermal expansion properties.
AB  - The hygroscopicity of Y2Mo3O12 has serious influences on its mechanic and
      negative thermal expansion (NTE) properties. The reported partial ion
      substitution for Y3+ in Y2Mo3O12 could reduce the hygroscopicity, however, the
      expected NTE properties disappear disappointedly. In this investigation, it is
      found that avoiding the invasion of crystal water and extending the NTE
      temperature range of Y2Mo3O12 to room temperature could be realized together by
      heating with CO(NH2)2. The X-ray diffraction patterns, infrared absorption
      spectra, scanning electron microscopy images and X-ray photoelectron spectra
      suggest the formation of small hydrophobic molecules (C3N4, C, etc.) coated on
      the surface, which could clog the microchannels in Y2Mo3O12 to avoid the invasion
      of crystal water. The investigation paves a way to improve the NTE properties by
      neglecting the influences of water molecules on the stretching vibrations of MoO4
      tetrahedra and the transverse vibrations of bridge oxygen atoms.

PMID- 28508916
TI  - Direct oral anticoagulants for the treatment of cancer-associated venous
      thromboembolism. What do we know so far?
AB  - Cancer patients with venous thromboembolism (VTE) are at increased risk for both
      bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin
      (LMWH) is the standard of care during the initial and long-term treatment phase
      (i.e. during the first 3 - 6 months of therapy) based on its overall beneficial
      safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct
      oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are
      approved for the treatment of acute VTE, and the combined six phase-3 trials have
      included > 1500 patients with active cancer, as defined by variable selection
      criteria. Subgroup analyses of these patients, either pooled or separately
      reported, suggest that DOACs could be a safe and efficacious alternative to VKA
      therapy for the treatment of cancer-associated VTE. However, the populations of
      cancer patients included in the DOAC and LMWH trials are not comparable with
      regard to mortality and VTE risk, and no specific data from direct head-to-head
      comparisons of DOACs with LMWHs are currently available. The use of DOACs for the
      management of VTE in cancer is thus not recommended by clinical practice
      guidelines.

PMID- 28508917
TI  - [Dowel pinning for metacarpal and metatarsal fractures in dogs].
AB  - OBJECTIVE: To evaluate a dowel pinning technique for metacarpal and metatarsal
      fractures in dogs. MATERIAL AND METHODS: Medical records of 13 dogs with complete
      clinical and radiographic follow-up examinations after a median observation time
      of 5 months were evaluated retrospectively. Assessment included fracture data,
      number of stabilized bones versus number of fractured bones and parameters of
      internal fixation including postoperative axial alignment and position of
      implants assessed on serial radiographs. Complications during the healing period
      and the final radiographic and functional outcome were analysed in relation to
      the details of fracture fixation. RESULTS: Most dogs in this study (mean age: 2.9
      years, mean weight: 9.9 kg) had fractures of three or four bones, and fractures
      were closed in all but one dog. All fractures involved the metacarpal/metatarsal
      body, and all but five were transverse. The size of Kirschner wires used for
      dowel pinning ranged from 0.8 to 2.0 mm, and the length in relation to bone
      length ranged from 39 to 91%. Axial alignment of internal fixation was and
      remained anatomically correct and the dowel pins remained in place in all but one
      dog. This dog had open metatarsal fractures and dowel pinning was
      contraindicated. Additionally, the Kirschner wires perforated the cortex of the
      proximal segments, which resulted in implant migration, malunion and residual
      lameness. The other dogs achieved complete functional union even though seven of
      13 dogs developed radiographic signs of synostosis. CLINICAL SIGNIFICANCE:
      Although the number of dogs in this study was small, dowel pinning was shown to
      be technically straightforward, inexpensive and effective for surgical repair of
      canine metacarpal and metatarsal bone fractures. Further studies should focus on
      the need for and duration of additional external coaptation.

PMID- 28508918
TI  - [Local anaesthesia in ruminants].
AB  - The use of local anaesthesia in ruminants allows many surgical procedures to be
      conducted free of pain, efficiently and inexpensively in the field. Local
      anaesthesia combined with sedation and immobilisation of the animal can replace
      general anaesthesia for many procedures (e. g. castration, claw amputation). The
      level of difficulty differs among various local anaesthetic techniques: local
      infiltration of tissue or anaesthesia of the cornual nerve are easily performed,
      whereas local anaesthesia of the eye, regional anaesthesia in limbs or
      anaesthesia for umbilical surgery are more difficult to carry out. This article
      presents an illustrated overview of the most common local anaesthetic procedures
      in cattle as well as in small ruminants and serves as a practical guide for
      veterinarians in the field. In principle, these techniques can likewise be
      applied in other ruminants or artiodactyls.

PMID- 28508919
TI  - Cognitive Development of School-Age Hypoplastic Left Heart Syndrome Survivors: A
      Single Center Study.
AB  - Neurological and radiologic research results show an abnormal cerebral
      microstructure as well as abnormal neurodevelopment in patients treated for
      hypoplastic left heart syndrome. The aim of this study was to assess the varying
      cognitive performance these children have developed in dependence upon prenatal
      diagnosis, surgical techniques, surgical learning effects, anatomy, perfusion
      techniques, gender, pedagogic, and sociodemographic parameters in comparison to
      age-adjusted normative values. School-age children (6.3-16.9 years) with
      hypoplastic left heart syndrome, who were treated at the Children's heart Center
      Linz between 1997 and 2009, (n = 74), were surveyed in reference to cognitive
      achievements. 43 patients were examined prospectively by psychologists using the
      Wechsler intelligence scale for children IV in order to determine the respective
      total intelligence quotient index for each child's developmental stage. The mean
      index was 84.5 (percentile rank 26.4). The statistical spread and standard
      deviation ranged from a minimum of 40 to a maximum of 134 +/- 20.8. The results
      for verbal comprehension, perceptual reasoning, and processing speed corresponded
      with total index results and were thus lower than the mean value of the normative
      values. The assessment of working memory showed results in the average. Prenatal
      diagnosis, type of lung perfusion, anatomy, and various cerebral perfusion
      techniques did not significantly affect the cognitive results of the patients.
      The results show that hypoplastic left heart syndrome patients can be
      successfully tutored formally as well as personally in cognitive areas, although
      when compared to healthy children, they showed lower results for intellectual
      area parameters.

PMID- 28508920
TI  - Chronic Low Dose Prostaglandin and Neonatal Heart Block.
AB  - Long-term prostaglandin use is commonly associated with side effects such as
      cortical proliferation of the bones, hypertrophic pyloric stenosis, and soft
      tissue swelling of the extremities. We report a neonate with critical coarctation
      of the aorta, who developed second and third degree atrioventricular blocks
      associated with prolonged prostaglandin E1 (PGE1) infusion. Interestingly, these
      conduction blocks only occurred at low PGE1 dose. The rhythm disturbances
      resolved promptly with the discontinuation of PGE1 following surgical repair.

PMID- 28508922
TI  - Adaptation and optimization of a fluorescence-based assay for in vivo
      antimalarial drug screening.
AB  - The in vivo efficacy of potential antimalarials is usually evaluated by direct
      microscopic determination of the parasitaemia of Plasmodium-infected mice on
      Giemsa-stained blood smears. This process is time-consuming, requires experienced
      technicians and is not automatable. Therefore, we optimized a SYBR Green I (SYBRG
      I) fluorescence-based assay to fluorometers commonly available in many research
      laboratories. This technique was originally developed to assess parasitaemia in
      humans by cytometry. We defined optimal conditions with Plasmodium berghei
      infected mice, standard lysis buffer (Tris, EDTA, saponin and Triton), whole
      blood cells and 2 h staining incubation with SYBRG I 2X. The fluorescence
      background generated by uninfected whole blood cells was low (around 4.6%), and
      the linearity high (r 2 = 0.96), with parasitaemia ranging from 1.4 to 60%. The
      Bland-Altman plot showed a strong correlation between SYBRG I and Giemsa gold
      standard method; Z'-factor was >0.5. These findings suggest that our fluorescence
      based assay is suitable for in vivo antimalarial drug assessment in a malaria
      murine model. It can help to overcome the human bias found with microscopic
      techniques.

PMID- 28508921
TI  - Latent factor structure of a behavioral economic marijuana demand curve.
AB  - RATIONALE: Drug demand, or relative value, can be assessed via analysis of
      behavioral economic purchase task performance. Five demand indices are typically
      obtained from drug purchase tasks. OBJECTIVES: The goal of this research was to
      determine whether metrics of marijuana reinforcement from a marijuana purchase
      task (MPT) exhibit a latent factor structure that efficiently characterizes
      marijuana demand. METHODS: Participants were regular marijuana users (n = 99;
      37.4% female, 71.5% marijuana use days [5 days/week], 15.2% cannabis dependent)
      who completed study assessments, including the MPT, during a baseline session.
      Principal component analysis was used to examine the latent structure underlying
      MPT indices. Concurrent validity was assessed via examination of relationships
      between latent factors and marijuana use, past quit attempts, and marijuana
      expectancies. RESULTS: A two-factor solution was confirmed as the best fitting
      structure, accounting for 88.5% of the overall variance. Factor 1 (65.8%
      variance) reflected "Persistence," indicating sensitivity to escalating marijuana
      price, which comprised four MPT indices (elasticity, O max, P max, and
      breakpoint). Factor 2 (22.7% variance) reflected "Amplitude," indicating the
      amount consumed at unrestricted price (intensity). Persistence factor scores were
      associated with fewer past marijuana quit attempts and lower expectancies of
      negative use outcomes. Amplitude factor scores were associated with more frequent
      use, dependence symptoms, craving severity, and positive marijuana outcome
      expectancies. CONCLUSIONS: Consistent with research on alcohol and cigarette
      purchase tasks, the MPT can be characterized with a latent two-factor structure.
      Thus, demand for marijuana appears to encompass distinct dimensions of price
      sensitivity and volumetric consumption, with differential relations to other
      aspects of marijuana motivation.

PMID- 28508923
TI  - Biomarkers of oxidative damage in bacteria for the assessment of sanitation
      efficacy in lettuce wash water.
AB  - In the fresh produce industry, validation of sanitation efficacy is critical to
      prevent cross-contamination of produce. The current validation approaches are
      either based on time-consuming plate counting assays or indirect measurements of
      chemical properties of wash water. In the study, the focus was to identify
      biomarkers that can provide direct assessment of oxidative damage in bacteria
      upon exposure to sanitizers in the presence of fresh produce and correlation of
      these oxidative biomarkers with logarithmic inactivation of bacteria. Two
      endogenous bacterial biomarkers, protein carbonylation and thiol oxidation, were
      evaluated for assessing oxidative damage in Escherichia coli O157:H7 and Listeria
      innocua during sanitation of pre-cut lettuce leaves with NaOCl or H2O2. Results
      show that NaOCl treatment was more effective than H2O2 for oxidation of both the
      intracellular thiols and protein carbonylation in the selected strains.
      Statistical analysis of the measurements illustrates that oxidation of the
      intracellular thiol induced by NaOCl or H2O2 was correlated with logarithmic
      reduction of E. coli O157:H7 and L. innocua. In contrast, changes in the protein
      carbonylation content were not correlated with reduction in bacterial cell
      viability. In summary, these results provide a novel approach to validate
      sanitation efficacy for the fresh produce industry.

PMID- 28508924
TI  - Intractable epistaxis: which arteries are responsible? An angiographic study.
AB  - PURPOSE: Epistaxis constitutes a significant proportion of the Otolaryngologist's
      emergency workload. Optimal management differs in relation to the anatomic origin
      of the bleeding. The outcome of our study was to determine which artery(ies)
      could be considered as the cause of severe bleeding in the context of severe
      epistaxis. METHODS: Fifty-five procedures of embolization preceded by angiography
      were reviewed. Medical records of interventionally treated patients were analysed
      for demographics, medical history, risk factors and clinical data. Angiographic
      findings were also assessed for active contrast extravasation (blush), vascular
      abnormality and embolised artery. RESULTS: Previous angiography showed an active
      contrast extravasation in only 20 procedures. The most common bleeding source was
      the sphenopalatine artery (SPA) followed by anterior ethmoidal artery (AEA) and
      facial artery. Majority of multiple or bilateral extravasations occured in
      patients with systemic factors. CONCLUSIONS: A better understanding of the
      potential bleeding source might help and limit the risk of treatment failures.
      Our study confirms that the SPA is the most common cause of severe bleeding. We
      also emphasise the role of the AEA not only in traumatic context. Others arteries
      are rarely involved except in patients with comorbidities or frequent
      recurrences.

PMID- 28508925
TI  - Using MALDI-TOF MS imaging and LC-HRMS for the investigation of the degradation
      of polycaprolactone diol exposed to different wastewater treatments.
AB  - Polymers are used in high amounts in a wide range of applications from
      biomedicine to industry. Because of the growing awareness of the increasing
      amounts of plastic wastes in the aquatic environment during recent years, the
      evaluation of their biodegradability deserves special attention. In the past,
      most efforts were dedicated to studying the biodegradation of polyesters in soil
      and compost, while very little research has been conducted on their fate in
      wastewater. Here, we assessed the ability of bacterial communities residing in
      the aerobic and denitrification tank from a wastewater treatment plant (WWTP) to
      degrade the polymeric ester polycaprolactone diol (PCLD; average molecular weight
      of 1250 Da). Following the incubation of the solid polymer in WWTP tanks, matrix
      assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was
      used to provide evidence for hydrolytic reactions and to study differences in the
      spatial degradation on the PCLD surface. It was demonstrated that regardless of
      the wastewater type, the chemical structure on the PCLD surface underwent
      modifications after 7 days of exposure. Apart from the parent PCLD peak series in
      MALDI-MSI mass spectra, the presence of a second oligomer series with mass peaks
      spaced by m/z 114 (as in PCLD) was observed. It was proposed to correspond to
      polycaprolactone (PCL) originating from the hydrolytic cleavage of the diethylene
      glycol from PCLD. Their ion masses were detected at m/z 104 below the PCLD peaks
      and their structures were proposed as PCL cyclized oligomers. Differences in the
      spatial distribution of low MW ions (<800) between the aerobic and denitrifying
      exposed samples in MALDI MSI were also noticeable. While the ions at m/z 221.1,
      247.1 and 449.2 predominated in the aerobic exposed sample, those at m/z 475.5
      and 677.4 were characteristic of the denitrifying one. The MALDI-MSI measurements
      in the low mass range were complemented with LC-HRMS analysis to determine
      plausible structures of the major degradation products. Ten transformation
      products (TPs) were detected in the denitrifying wastewater experiment, five of
      them were the result of ester hydrolysis forming caprolactone oligomers (TPs 220,
      334, 448, 562, and 676) while the other series corresponded to formation of PCL
      chain with a terminal diethylene glycol, likewise formed by ester hydrolysis (TPs
      246, 360, 474, 588, and 702). Graphical abstract Investigation of the polymer
      degradation in WWTPs by MALDI-MSI and LC-HRMS.

PMID- 28508926
TI  - Abundance and Co-Distribution of Widespread Marine Archaeal Lineages in Surface
      Sediments of Freshwater Water Bodies across the Iberian Peninsula.
AB  - Archaea inhabiting marine and freshwater sediments have a relevant role in
      organic carbon mineralization, affecting carbon fluxes at a global scale. Despite
      current evidences suggesting that freshwater sediments largely contribute to this
      process, few large-scale surveys have been addressed to uncover archaeal
      diversity and abundance in freshwater sedimentary habitats. In this work, we
      quantified and high-throughput sequenced the archaeal 16S rRNA gene from
      surficial sediments collected in 21 inland waterbodies across the Iberian
      Peninsula differing in typology and trophic status. Whereas methanogenic groups
      were dominant in most of the studied systems, especially in organic-rich
      sediments, archaea affiliated to widespread marine lineages (the Bathyarchaeota
      and the Thermoplasmata) were also ubiquitous and particularly abundant in euxinic
      sediments. In these systems, Bathyarchaeota communities were dominated by
      subgroups Bathyarchaeota-6 (87.95 +/- 12.71%) and Bathyarchaeota-15 (8.17 +/-
      9.2%) whereas communities of Thermoplasmata were mainly composed of members of
      the order Thermoplasmatales. Our results also indicate that Archaea accounted for
      a minor fraction of sedimentary prokaryotes despite remarkable exceptions in
      reservoirs and some stratified lakes. Copy numbers of archaeal and
      bathyarchaeotal 16S rRNA genes were significantly different when compared
      according to system type (i.e., lakes, ponds, and reservoirs), but no differences
      were obtained when compared according to their trophic status (from oligotrophy
      to eutrophy). Interestingly, we obtained significant correlations between the
      abundance of reads (Spearman r = 0.5, p = 0.021) and OTU richness (Spearman r =
      0.677, p < 0.001) of Bathyarchaeota and Thermoplasmata across systems,
      reinforcing the hypothesis of a potential syntrophic interaction between members
      of both lineages.

PMID- 28508927
TI  - Tumor LXR Expression is a Prognostic Marker for Patients with Hepatocellular
      Carcinoma.
AB  - Liver X receptor (LXR) activation exerts an anti-tumor effect. However, whether
      the tumor LXR expression has prognostic significance in hepatocellular carcinoma
      (HCC) patient has not been addressed yet. Primary HCC and the adjacent non-tumor
      tissues were obtained from 169 patients who underwent routine curative surgical
      treatment. All patients were followed for prognosis analyses. Tumor LXR was
      detected by immunohistochemical analysis. In in vitro study, several HCC cell
      lines were cultured for cellular protein detection of LXR and other cytokines,
      including nuclear factor kappa (NFkappaB), Matrix metalloproteinases 2 and 9 (MMP
      2 and -9). Meanwhile, the invasion ability of cultured HCC cell lines was
      performed. We found that LXR expression status in tumor samples is associated
      with the clinical characteristics, such as tumor stage and metastasis, of HCC
      patients. Prognosis analysis shows that tumor LXR expression status is closely
      related to the post-operative outcome in HCC patients who underwent surgical
      treatment. Patients with low LXR expression have a significantly lower mean 5
      year overall survival rate and mean overall survival period than those with high
      LXR level. Our in vitro data reveal that HCC cell lines had increased NF-kappaB,
      MMP2, MMP9 and invasive ability than normal cell line, which are suppressed by
      LXR activation via NFkappaB pathway. Our data suggest that LXR could be used as a
      biomarker for HCC prognosis. Further study is warranted to explore the molecular
      mechanism under which LXR regulates tumor behaves.

PMID- 28508928
TI  - Embryonal tumors in Canadian children less than 36 months of age: results from
      the Canadian Pediatric Brain Tumor Consortium (CPBTC).
AB  - Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors
      whose subgroups have varying incidence and outcome. Despite these differences,
      they are often grouped as a single entity for study purposes. To date, there are
      no Canadian multi-institutional studies examining the incidence and outcome of
      all embryonal subtypes. The current study is an observational study reviewing
      embryonal tumors in all patients less than 36 months of age diagnosed with a CNS
      tumor in Canada from 1990 to 2005. Embryonal tumors accounted for 26.9% of all
      CNS tumors. Medulloblastomas were the highest proportion of the embryonal tumors
      at 61.5%. Atypical teratoid/rhabdoid tumors (AT/RT) had the second highest
      proportion of embryonal tumors at 18%. The proportion of primitive
      neuroectodermal tumors (PNET) was 16%, with 2.6 and 1.9% for congenital
      medulloepithelioma and ependymoblastoma tumors, respectively. AT/RT and PNET were
      more common in younger age groups. Medulloblastoma became more prevalent with
      increasing age, with its highest prevalence in the 25 to 36 month age group.
      Survival rates for our Canadian population at 18 and 24 months were 0.74 and 0.68
      for medulloblastoma, 0.64 and 0.60 for PNET, and 0.36 and 0.29 for AT/RT,
      respectively. Overall, our data are comparable with published international rates
      for embryonal tumors. These incidence and outcome figures can guide future
      research into these rare tumors.

PMID- 28508929
TI  - Untargeted metabolomic analysis of tomato pollen development and heat stress
      response.
AB  - KEY MESSAGE: Pollen development metabolomics. Developing pollen is among the
      plant structures most sensitive to high temperatures, and a decrease in pollen
      viability is often associated with an alteration of metabolite content. Most of
      the metabolic studies of pollen have focused on a specific group of compounds,
      which limits the identification of physiologically important metabolites. To get
      a better insight into pollen development and the pollen heat stress response, we
      used a liquid chromatography-mass spectrometry platform to detect secondary
      metabolites in pollen of tomato (Solanum lycopersicum L.) at three developmental
      stages under control conditions and after a short heat stress at 38  degrees C.
      Under control conditions, the young microspores accumulated a large amount of
      alkaloids and polyamines, whereas the mature pollen strongly accumulated
      flavonoids. The heat stress treatment led to accumulation of flavonoids in the
      microspore. The biological role of the detected metabolites is discussed. This
      study provides the first untargeted metabolomic analysis of developing pollen
      under a changing environment that can serve as reference for further studies.

PMID- 28508931
TI  - Kafka and Autism : The Undisclosed Logic Behind Kafka's Work.
AB  - In this paper the hypothesis is presented that Franz Kafka was a person with
      autism. This is done by analyzing and discussing his biography, letters, diaries
      and major works. Kafka's autism is an integral diagnosis which encompasses both
      his personal life and his work. This interpretation is contrary to other
      interpretations from the past which in all cases were only partially applicable
      to explain Kafka's life and work. In Kafka research the big secret of Kafka was
      how he was able to write he did, like no one before him had done. The function
      and use of parables are also discussed to support this autism hypothesis
      concerning Franz Kafka which ultimately makes his life and work more
      understandable and accessible.

PMID- 28508930
TI  - Assessing Psychological Insulin Resistance in Type 2 Diabetes: a Critical
      Comparison of Measures.
AB  - PURPOSE OF REVIEW: This study aims to examine the operationalisation of
      'psychological insulin resistance' (PIR) among people with type 2 diabetes and to
      identify and critique relevant measures. RECENT FINDINGS: PIR has been
      operationalised as (1) the assessment of attitudes or beliefs about insulin
      therapy and (2) hypothetical or actual resistance, or unwillingness, to use to
      insulin. Five validated PIR questionnaires were identified. None was fully
      comprehensive of all aspects of PIR, and the rigour and reporting of
      questionnaire development and psychometric validation varied considerably between
      measures. Assessment of PIR should focus on the identification of negative and
      positive attitudes towards insulin use. Actual or hypothetical insulin refusal
      may be better conceptualised as a potential consequence of PIR, as its assessment
      overlooks the attitudes that may prevent insulin use. This paper provides
      guidance on the selection of questionnaires for clinical or research purpose and
      the development of new, or improvement of existing, questionnaires.

PMID- 28508932
TI  - Enterovirus-Related Immune Reconstitution Inflammatory Syndrome (IRIS) Following
      Haploidentical Stem Cell Transplantation in an MHC Class II-Deficient Child.

PMID- 28508934
TI  - Xanthomatous macrophages in bone marrow biopsies: systemic manifestation of
      mycobacterioses.

PMID- 28508933
TI  - Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms:
      Effects on Antipsychotic Response and Schizophrenia Psychopathology in a
      Naturalistic Treatment Setting in Two Independent Korean and Italian Samples.
AB  - INTRODUCTION: Schizophrenia (SCZ) is one of the most disabling psychiatric
      disorders. Genetic factors play an important role in both SCZ liability and its
      treatment outcome. In the present paper, we investigated the effects of several
      single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved
      with antipsychotics (APs) mechanisms of action. METHODS: Two independent samples
      were investigated in the present study. Totals of 176 SCZ subjects and 326
      controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian
      ancestry were recruited and genotyped. SCZ risk and other parameters were also
      investigated. RESULTS: Concerning APs response, only a nominal association with
      HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis,
      rs9801117 C-rs12668837 C-rs4621754 A haplotype within ESYT2 and NCAPG2 genes was
      associated with APs response in the same sample. As for secondary outcomes,
      rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in
      the Italian sample. In the haplotype analysis, rs2788478 G-rs2657375 T-rs1039621
      A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)-rs6459896 A
      (NCAPG2) haplotypes were associated with SCZ in the same sample. No association
      was found in the Korean sample. Finally, our exploratory data suggest a possible
      modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs
      response to specific symptom clusters. CONCLUSION: Our results did not support a
      primary role for the genes investigated in the APs response. On the other hand,
      our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ
      liability. Finally, our exploratory findings may deserve further investigations
      in specific studies.

PMID- 28508935
TI  - Successful treatment of calcineurin inhibitor-induced pain syndrome with acute
      graft versus host disease by switching calcineurin inhibitors followed by
      pregabalin.

PMID- 28508936
TI  - Phase I Clinical Study of ZYAN1, A Novel Prolyl-Hydroxylase (PHD) Inhibitor to
      Evaluate the Safety, Tolerability, and Pharmacokinetics Following Oral
      Administration in Healthy Volunteers.
AB  - OBJECTIVE: This phase I study of ZYAN1 was conducted to evaluate the safety,
      tolerability, and pharmacokinetics following oral administration in healthy
      volunteers. METHODS: The study was a randomized, double-blind, placebo-controlled
      phase I study carried out in two parts in addition to a third part involving an
      open-label study to evaluate the food/sex effect. A total of 100 subjects were
      enrolled into the study as follows: part I-single-dose study with ZYAN1 10, 25,
      50, 100, 150, 200, and 300 mg (n = 56); part II-multiple-dose study with every
      other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32); and part III-sex
      and food effect study with ZYAN1 150 mg (n = 12; open-label). RESULTS: ZYAN1 was
      well-tolerated after single and multiple oral ascending doses. No drug-related
      serious adverse events were reported. Following a single ascending dose of ZYAN1,
      the maximum concentration (C max) ranged from 566.47 +/- 163.03 to 17,858.33 +/-
      2899.19 ng/mL and the median time to C max (t max) was approximately 2.5 h for
      the studied 30-fold oral doses of ZYAN1. Regardless of single or multiple doses,
      mean C max and area under the concentration-time curve from time zero to time t
      (AUC t ) values generally showed a dose-proportional increase. The mean
      elimination half-life (t 1/2) of ZYAN1 ranged from 6.9 to 13 h with negligible
      accumulation. Following a single dose of ZYAN1, the mean serum erythropoietin
      (EPO) C max values showed dose response (i.e., 6.6 and 79.9 mIU/L for 10 and 300
      mg ZYAN1 doses, respectively), while the time to mean maximal serum EPO
      concentrations ranged from 10 to 72 h. CONCLUSION: Oral single (10-300 mg) and
      multiple dosing (100-300 mg) of ZYAN1 in healthy subjects was found to be safe
      and well-tolerated. With increasing ZYAN1 dose, there was almost a proportional
      increase in mean C max and AUC t . The mean serum EPO concentrations showed a
      trend of dose response. Based on the t 1/2, pharmacodynamic activity, and lack of
      drug accumulation, a once every 2 days dosing regimen of ZYAN1 was appropriate
      for phase II study. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry trial ID ACTRN12614001240639.

PMID- 28508937
TI  - The Prevalence of Oropharyngeal Dysphagia in Adults Presenting with
      Temporomandibular Disorders Associated with Rheumatoid Arthritis: A Systematic
      Review and Meta-analysis.
AB  - Temporomandibular disorders (TMDs) are the most frequent non-dental orofacial
      pain disorders and may be associated with rheumatoid arthritis (RA), resulting in
      oropharyngeal dysphagia (OD). However, clinicians' understanding of involvement
      with OD caused by RA-related TMDs is limited and the methodological quality of
      research in this field has been criticised. Therefore, the aim of this study was
      to systematically review the prevalence of oral preparatory and oral stage signs
      and symptoms of OD in adults presenting with TMDs associated with RA. A
      systematic review of the literature was completed. The following electronic
      databases were searched from inception to February 2016, with no date/language
      restriction: EMBASE, PubMed, CINAHL, Web of Science, Elsevier Scopus, Science
      Direct, AMED, The Cochrane Database of Systematic Reviews, and ProQuest
      Dissertations and Theses A & I. Grey literature and reference lists of the
      included studies were also searched. Studies reporting the frequency of OD in
      adults presenting with TMD and RA were included. Study eligibility and quality
      were assessed by three independent reviewers. Methodological quality was assessed
      using the Down's and Black tool. The search yielded 19 eligible studies. Typical
      difficulties experienced by RA patients included impaired swallowing (24.63%),
      impaired masticatory ability (30.69%), masticatory pain (35.58%), and masticatory
      fatigue (21.26%). No eligible studies reported figures relating to the prevalence
      of weight loss. Eligible studies were deemed on average to be of moderate
      quality. Study limitations included the small number of studies which met the
      inclusion criteria and the limited amount of studies utilising objective
      assessments. Valid and reliable prospective research is urgently required to
      address the assessment and treatment of swallowing difficulties in RA as TMJ
      involvement may produce signs and symptoms of OD.

PMID- 28508939
TI  - [The worlds of gods in medicine].
AB  - BACKGROUND: A number of designations for diseases, medicines and human body
      structures derive from classical mythology. To date, these eponyms have not been
      systematically investigated. OBJECTIVES: This paper provides an overview of this
      fringe component of medical vocabulary, looks at the history of several terms and
      formulates hypotheses as to why such creative etymologies have come into being.
      MATERIALS AND METHODS: In addition to relevant texts on ancient mythology, a
      variety of medical textbooks from the early modern period were analyzed. RESULTS:
      Between the 16th and the 20th centuries some 30 figures from Greek and Roman
      literature made their way into the terminology of medical sciences. A few of
      these expressions can be encountered in clinical use (e. g., Caput Medusae,
      Proteus, Oedipus complex) and remain official anatomical (atlas, Achilles tendon)
      or pharmaceutical nomenclature (atropine, morphine). The choice of these
      designations has often been similarity of form or analogies in function.
      Classical eponyms have gained acceptance on account of their succinctness,
      conciseness and scholarly veneer. Finally, this vocabulary shares its origin with
      other relevant terminology. CONCLUSIONS: In clinical classes, mythological
      designations can serve as a point of departure for digressions into literary, art
      and medical history in order to provide an understanding of cultural traditions
      and enhance education.

PMID- 28508941
TI  - [Unusual tumor of the kidney].

PMID- 28508938
TI  - Immunotherapy for the Treatment of Uveal Melanoma: Current Status and Emerging
      Therapies.
AB  - PURPOSE OF REVIEW: Uveal melanoma is a distinct subset of melanoma with a biology
      and treatment approach that is unique from that of cutaneous melanoma. Here we
      will review the current data evaluating immunotherapies in both the adjuvant and
      metastatic settings in uveal melanoma. RECENT FINDINGS: In the adjuvant setting,
      interferon demonstrated no survival benefit in uveal melanoma, and studies
      evaluating immune-based strategies such as vaccine therapy are ongoing. Anti-CTLA
      4 and anti-PD-1/ PD-L1 blockade in uveal melanoma have been evaluated in several
      small prospective and/or retrospective studies with rare responses and no overall
      survival benefit demonstrated. Ongoing studies evaluating combination checkpoint
      inhibition and other antibody-based therapies are ongoing. Although immunotherapy
      with anti-CTLA-4 and anti-PD-1 agents has dramatically changed the treatment
      approach to cutaneous melanoma, its success in uveal melanoma has been much more
      limited. Clinical trial participation should be prioritized in patients with
      uveal melanoma.

PMID- 28508942
TI  - [Conservative and surgical ileus treatment].
AB  - The diagnosis ileus is one of the most common indications for an emergency
      laparotomy. In 70% of the cases, the small intestine is affected, and in 30% it
      is the colorectum. While stuck hernias are a major cause in developing countries,
      the most common causes in western countries are postoperative adhesions that lead
      to an acute bowl obstruction. The timeframe for treatment of a complete
      mechanical obstruction is short as acute ischemia can lead to necrosis with bowl
      perforation within 6 h. The perioperative lethality for an emergency laparotomy
      due to an ileus ranges from 5-15%. In addition to the mechanical ileus, primary
      and secondary paralytic ileus is important in the differential diagnosis. As the
      genesis of postoperative ileus is multifactorial, a multimodal concept is
      required for successful treatment.

PMID- 28508944
TI  - Suppressive effects of zingerone on TGFBIp-mediated septic responses.
AB  - Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to
      possess various pharmacological activities. Transforming growth factor beta
      induced protein (TGFBIp) is an extracellular matrix protein whose expression in
      several cell types is greatly increased by TGF-beta. TGFBIp is released by human
      umbilical vein endothelial cells and functions as a mediator of experimental
      sepsis. We hypothesized that ZGR could reduce TGFBIp-mediated severe inflammatory
      responses in human endothelial cells and mice. Here, we investigated the anti
      septic effects and underlying mechanisms of ZGR against TGFBIp-mediated septic
      responses. ZGR effectively inhibited lipopolysaccharide-induced release of TGFBIp
      and suppressed TGFBIp-mediated septic responses. In addition, ZGR suppressed
      TGFBIp-induced sepsis lethality and pulmonary injury. In conclusion, ZGR
      suppressed TGFBIp-mediated and CLP-induced septic responses. Therefore, ZGR could
      be a potential therapeutic agent for treatment of various severe vascular
      inflammatory diseases via inhibition of the TGFBIp signaling pathway.

PMID- 28508943
TI  - Perceived ethnic discrimination in relation to smoking and alcohol consumption in
      ethnic minority groups in The Netherlands: the HELIUS study.
AB  - OBJECTIVES: We examined the associations of perceived ethnic discrimination (PED)
      with smoking and alcohol consumption in ethnic minority groups residing in a
      middle-sized European city. METHODS: Data were derived from the HELIUS study in
      Amsterdam, The Netherlands. We included 23,126 participants aged 18-70 years of
      Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and
      Moroccan origin. We collected self-reported data on PED, current smoking, heavy
      smoking, nicotine dependence, current drinking, excessive drinking, and alcohol
      dependence. Logistic regression was used. RESULTS: In general, we observed
      positive associations in participants of African Surinamese and Ghanaian origin,
      but no associations in those of South-Asian Surinamese, Turkish, or Moroccan
      origin. In African Surinamese, the associations were positive for current
      smoking, nicotine, and alcohol dependence (odds ratios of 1.16; 95% confidence
      interval: 1.06-1.27, 1.34; 1.15-1.57 and 1.40; 1.20-1.64, respectively). In
      Ghanaians, positive association was observed for current drinking (1.21; 1.08
      1.36). CONCLUSIONS: The associations of PED with smoking and alcohol consumption
      considerably varied by ethnicity and outcome measure. This suggests that ethnic
      minority groups in Europe might use different behavioural strategies to cope with
      PED.

PMID- 28508946
TI  - Using principal component analysis and annual seasonal trend analysis to assess
      karst rocky desertification in southwestern China.
AB  - Increasing exploitation of karst resources is causing severe environmental
      degradation because of the fragility and vulnerability of karst areas. By
      integrating principal component analysis (PCA) with annual seasonal trend
      analysis (ASTA), this study assessed karst rocky desertification (KRD) within a
      spatial context. We first produced fractional vegetation cover (FVC) data from a
      moderate-resolution imaging spectroradiometer normalized difference vegetation
      index using a dimidiate pixel model. Then, we generated three main components of
      the annual FVC data using PCA. Subsequently, we generated the slope image of the
      annual seasonal trends of FVC using median trend analysis. Finally, we combined
      the three PCA components and annual seasonal trends of FVC with the incidence of
      KRD for each type of carbonate rock to classify KRD into one of four categories
      based on K-means cluster analysis: high, moderate, low, and none. The results of
      accuracy assessments indicated that this combination approach produced greater
      accuracy and more reasonable KRD mapping than the average FVC based on the
      vegetation coverage standard. The KRD map for 2010 indicated that the total area
      of KRD was 78.76 * 103 km2, which constitutes about 4.06% of the eight southwest
      provinces of China. The largest KRD areas were found in Yunnan province. The
      combined PCA and ASTA approach was demonstrated to be an easily implemented,
      robust, and flexible method for the mapping and assessment of KRD, which can be
      used to enhance regional KRD management schemes or to address assessment of other
      environmental issues.

PMID- 28508945
TI  - Clinical efficacy of percutaneous cryoablation combined with allogenic NK cell
      immunotherapy for advanced non-small cell lung cancer.
AB  - In this study, the safety and clinical efficacy of cryosurgery combined with
      allogenic NK cell immunotherapy for the treatment of advanced non-small cell lung
      cancer (NSCLC) were evaluated. From July 2016 to March 2017, we enrolled 60
      patients who met the enrollment criteria and divided them into two groups: (1)
      the simple cryoablation group (n = 30) and (2) the cryoablation combined with
      allogenic NK cell group (n = 30). The changes in immune function, quality of
      life, and clinical response were evaluated. We found that allogenic NK cells
      combined with cryosurgical treatment for advanced NSCLC have a synergistic
      effect, which not only enhancing the immune function of patients, improving the
      quality of life, and significantly increasing the response rate (RR) and disease
      control rate (DCR) compared to cryoablation group. This study is the first
      clinical trial of allogenic NK cells combined with cryosurgery for the treatment
      of advanced NSCLC and preliminaily its safety and efficacy.

PMID- 28508949
TI  - Zn(II)-dipicolylamine-based metallo-lipids as novel non-viral gene vectors.
AB  - In this study, a series of Zn(II)-dipicolylamine (Zn-DPA) based cationic lipids
      bearing different hydrophobic tails (long chains, alpha-tocopherol, cholesterol
      or diosgenin) were synthesized. Structure-activity relationship (SAR) of these
      lipids was studied in detail by investigating the effects of several structural
      aspects including the type of hydrophobic tails, the chain length and saturation
      degree. In addition, several assays were used to study their interactions with
      plasmid DNA, and results reveal that these lipids could condense DNA into
      nanosized particles with appropriate size and zeta-potentials. MTT-based cell
      viability assays showed that lipoplexes 5 had low cytotoxicity. The in vitro gene
      transfection studies showed the hydrophobic tails clearly affected the TE, and
      hexadecanol-containing lipid 5b gives the best TE, which was 2.2 times higher
      than bPEI 25k in the presence of 10% serum. The results not only demonstrate that
      these lipids might be promising non-viral gene vectors, but also afford us clues
      for further optimization of lipidic gene delivery materials.

PMID- 28508947
TI  - Podocytes from the diagnostic and therapeutic point of view.
AB  - The central role of podocytes in glomerular diseases makes this cell type an
      interesting diagnostic tool as well as a therapeutic target. In this review, we
      discuss the current literature on the use of podocytes and podocyte-specific
      markers as non-invasive diagnostic tools in different glomerulopathies.
      Furthermore, we highlight the direct effects of drugs currently used to treat
      primary glomerular diseases and describe their direct cellular effects on
      podocytes. A new therapeutic potential is seen in drugs targeting the podocytic
      actin cytoskeleton which is essential for podocyte foot process structure and
      function. Incubation of cultured human podocyte cell lines with sera from
      patients with active glomerular diseases is currently also used to identify novel
      circulating factors with pathophysiological relevance for the glomerular
      filtration barrier. In addition, treatment of detached urinary podocytes from
      patients with substances that restore their cytoskeleton might serve as a novel
      personalized tool to estimate their potential for podocyte recovery ex vivo.

PMID- 28508950
TI  - Malignancy as a comorbidity in rheumatic diseases: a retrospective hospital-based
      study.
AB  - Patients with Rheumatic diseases (RDs) are at an increased risk of malignancies
      compared with the general population. The aim of this study was to examine the
      relative frequency of several cancers in a single homogeneous cohort of patients
      with different RDs. Patients diagnosed with rheumatoid arthritis (RA), Ankylosing
      spondylitis (AS), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE),
      systemic sclerosis (SSc), dermatomyositis (DM), or polymyositis were included.
      Out of 3982 adult residents admitted to the division of rheumatology, 61
      malignancies were observed. The 2009 National Central Cancer Registry (NCCR) of
      China served as the reference for calculating standardized ratio (SR). The
      malignancy frequency had no difference between RDs with malignancy and the
      general population. Patients with SS and DM/PM showed an increased risk of non
      Hodgkin's lymphoma (SR for SS patients = 9.709, 95% confidence interval (CI) =
      4.602 to 17.916; SR for DM/PM = 35.714, 95% CI = 25.001 to 49.527). Patients with
      DM/PM and SSc showed an increased risk of lung cancer (SR for DM/PM = 10.638, 95%
      CI = 5.245 to 19.131; SR for SSc patients = 7.752, 95% CI = 3.295 to 15.309).
      Patients with SS and DM/PM showed an increased risk of ovary cancer (SR for SS
      patients = 8.177, 95% CI = 3.566 to 15.888; SR for DM/PM = 32.258, 95% CI =
      22.126 to 45.490). Patients with SLE showed an increased risk of cervix cancer
      (SR for AS patients = 6.897, 95% CI = 2.748 to 14.144). Patients with AS showed
      an increased risk of pancreas cancer (SR for AS patients = 7.576, 95% CI = 2.181
      to 15. 071). Different RDs have an increased risk of particular cancers. Among
      hematologic cancers, the risk of non-Hodgkin's lymphoma was higher than general
      population. Among solid tumors, the risk of cancers of the lung, ovary, cervix,
      and pancreas was higher than general population.

PMID- 28508951
TI  - Magnesium ions enhance infiltration of osteoblasts in scaffolds via increasing
      cell motility.
AB  - Magnesium (Mg) ions are the most abundant intracellular divalent cations and play
      a pivotal role in numerous cellular processes. Biodegradable Mg-containing
      materials, including scaffolds, are promising candidates for orthopedic
      applications. Here, we investigated the effect of Mg ions on the cellular
      properties of osteoblasts. Cytotoxicity tests on osteoblasts confirmed that no
      cytotoxic effects were found up to a supplementing Mg ion concentration of 10 mM.
      Mg ions at a concentration of 5 mM increased the migration and invasiveness of
      osteoblasts. To investigate the stimulatory effect of Mg ions on cell motility in
      scaffolds, we fabricated 10 wt% Mg ion-containing polycaprolactone (PCL)
      scaffolds, using the wire-network molding (WNM) technique. Mg ion-containing
      scaffolds persistently released Mg ions at a concentration of 5 mM in the media
      after pre-incubation. Furthermore, increased cell motility was confirmed in Mg
      ion-containing scaffolds by quantification of genomic DNA and protein content.
      Our results provide an important basis for the function of Mg ions and their
      effect on cell motility, and propose a novel role for Mg ions in scaffold
      applications.

PMID- 28508952
TI  - Identification of Sex-determining Loci in Pacific White Shrimp Litopeneaus
      vannamei Using Linkage and Association Analysis.
AB  - The Pacific white shrimp Litopenaeus vannamei is a predominant aquaculture shrimp
      species in the world. Like other animals, the L. vannamei exhibited sexual
      dimorphism in growth trait. Mapping of the sex-determining locus will be very
      helpful to clarify the sex determination system and further benefit the shrimp
      aquaculture industry towards the production of mono-sex stocks. Based on the data
      used for high-density linkage map construction, linkage-mapping analysis was
      conducted. The sex determination region was mapped in linkage group (LG) 18. A
      large region from 0 to 21.205 cM in LG18 showed significant association with sex.
      However, none of the markers in this region showed complete association with sex
      in the other populations. So an association analysis was designed using the
      female parent, pool of female progenies, male parent, and pool of male progenies.
      Markers were de novo developed and those showing significant differences between
      female and male pools were identified. Among them, three sex-associated markers
      including one fully associated marker were identified. Integration of linkage and
      association analysis showed that the sex determination region was fine-mapped in
      a small region along LG18. The identified sex-associated marker can be used for
      the sex detection of this species at genetic level. The fine-mapped sex
      determining region will contribute to the mapping of sex-determining gene and
      help to clarify sex determination system for L. vannamei.

PMID- 28508953
TI  - [Mycotoxins in food : Occurrence, importance and health risk].
AB  - Mycotoxins are produced by a variety of fungal species on crops or stored
      commodities; they appear as primary or secondary contaminants and via the
      carryover effect in the food chain. The global occurrence of many mycotoxins with
      a wide spectrum of toxicities is the subject of interdisciplinary research and a
      relevant topic for consumer protection. This overview aims to raise interest with
      sections of the hazardous properties of important mycotoxins (from aflatoxin to
      zearalenone) and describes recent developments in the area of exposure assessment
      and basic principles applied in risk characterization. Challenges with regard to
      new insights about modified and so far unregulated mycotoxins are also addressed.

PMID- 28508954
TI  - [Perceived risks of food contaminants].
AB  - BACKGROUND: Food contaminants can pose a serious health threat. In order to carry
      out adequate risk communication measures, the subjective risk perception of the
      public must be taken into account. In this context, the breadth of the topic and
      insufficient terminological delimitations from residues and food additives make
      an elaborate explanation of the topic to consumers indispensable. A
      representative population survey used language adequate for lay people and a
      clear definition of contaminants to measure risk perceptions with regard to food
      contaminants among the general public. OBJECTIVES: The study aimed to assess
      public awareness of contaminants and the perceived health risks associated with
      them. In addition, people's current knowledge and need for additional
      information, their attitudes towards contaminants, views on stakeholder
      accountability, as well as compliance with precautionary measures, such as
      avoiding certain foods to reduce health risks originating from contaminants, were
      assessed. MATERIALS AND METHODS: A representative sample of 1001 respondents was
      surveyed about food contaminants via computer-assisted telephone interviewing.
      RESULTS: The majority of respondents rated contaminants as a serious health
      threat, though few of them spontaneously mentioned examples of undesirable
      substances in foods that fit the scientific or legal definition of contaminants.
      Mercury and dioxin were the most well-known contaminants. Only a minority of
      respondents was familiar with pyrrolizidine alkaloids. CONCLUSIONS: The present
      findings highlight areas that require additional attention and provide
      implications for risk communication geared to specific target groups.

PMID- 28508955
TI  - [How does a pesticide residue turn into a contaminant?]
AB  - Over the last few years pesticide residues have been repeatedly detected during
      official food controls that would not be expected from authorized pesticide uses.
      These residues do not always pose a health risk for consumers. However, the legal
      and economic consequences of such findings are often far-reaching, especially if
      the admissible maximum residue limits have been fixed at the LOQ level only. For
      some example cases, we discuss the real entry pathways into the food chain and
      under which circumstances residues of such unintentionally added substances could
      be better regulated under the contaminant legal framework rather than the
      pesticide legal framework.

PMID- 28508956
TI  - Doctors' attitudes towards the introduction and clinical operation of do not
      resuscitate orders (DNRs) in Ireland.
AB  - BACKGROUND: Do not resuscitate orders (DNRs) are documents which state that
      should a patient suffer from cardiopulmonary failure, resuscitation should not be
      attempted. Internationally, DNRs are often misunderstood and used inappropriately
      in a clinical setting. AIMS: The aim of this paper was to determine the current
      understanding of DNRs and their clinical operation among hospital doctors in
      Ireland. METHODS: A cross-sectional, questionnaire-based study was conducted
      involving doctors from the Cork teaching hospitals. The questionnaire sought
      information regarding understanding of DNRs and their clinical operation, as well
      as attitudes regarding the current absence of relevant Irish guidelines. The
      questionnaire also collected information regarding demographics, clinical
      specialty, and level of experience. RESULTS: 45.9% (47/103) of all doctors stated
      that their clinical knowledge was sufficient to draft a DNR, but 48.7% of this
      group (n = 23) chose the incorrect definition for a DNR when provided with three
      separate options. Thirty-five percent (n = 36) of all doctors surveyed
      demonstrated an incorrect understanding of a DNR. Neither specialty nor
      experience level had any effect on level of understanding of DNRs (p > 0.05).
      93.2% (n = 96) agreed that there is a need for introduction of domestic
      guidelines regarding DNRs. 57.6% (n = 59) would draft more DNRs in the event that
      such domestic guidelines were in place. CONCLUSIONS: A substantial proportion of
      hospital doctors surveyed demonstrated an incomplete understanding of DNRs and
      their clinical operation. However, the overwhelming majority of the present
      sample believe that domestic guidelines are needed on the matter.

PMID- 28508958
TI  - Modeling the critical care pathway for cardiothoracic surgery.
AB  - The west of Scotland heart and lung center based at the Golden Jubilee National
      Hospital houses all adult cardiothoracic surgery for the region. Increased demand
      for scheduled patients and fluctuations in emergency referrals resulted in
      increasing waiting times and patient cancellations. The main issue was limited
      resources, which was aggravated by the stochastic nature of the length of stay
      (LOS) and arrival of patients. Discrete event simulation (DES) was used to assess
      if an enhanced schedule was sufficient, or more radical changes, such as capacity
      or other resource reallocations should be considered in order to solve the
      problem. Patients were divided into six types depending on their condition and
      LOS at the different stages of the process. The simulation model portrayed each
      patient type's pathway with sufficient detail. Patient LOS figures were analyzed
      and distributions were formed from historical data, which were then used in the
      simulation. The model proved successful as it showed figures that were close to
      actual observations. Acquiring results and knowing exactly when and what caused a
      cancellation was another strong point of the model. The results demonstrated that
      the bottleneck in the system was related to the use of High Dependency Unit (HDU)
      beds, which were the recovery beds used by most patients. Enhancing the schedule
      by leveling out the daily arrival of patients to HDUs reduced patient
      cancellations by 20%. However, coupling this technique with minor capacity
      reallocations resulted in more than 60% drop in cancellations.

PMID- 28508957
TI  - Genetic and environmental correlations between subjective wellbeing and
      experience of life events in adolescence.
AB  - Some life events appear heritable due to the genetic influence on related
      behaviours. Shared genetic influence between negative behaviours and negative
      life events has previously been established. This study investigated whether
      subjective wellbeing and positive life events were genetically associated.
      Participants in the Twins Early Development Study (aged 16.32 +/- .68 years)
      completed subjective wellbeing and life events assessments via two separate
      studies (overlapping N for wellbeing and life events measures ranged from 3527 to
      9350). We conducted bivariate twin models between both positive and negative life
      events with subjective wellbeing and related positive psychological traits
      including subjective happiness, life satisfaction, optimism, hopefulness and
      gratitude measured at 16 years. Results suggested that the heritability of life
      events can partially be explained by shared genetic influences with the wellbeing
      indicators. Wellbeing traits were positively genetically correlated with positive
      life events and negatively correlated with negative life events (except curiosity
      where there was no correlation). Those positive traits that drive behaviour (grit
      and ambition) showed the highest genetic correlation with life events, whereas
      the reflective trait gratitude was less correlated. This suggests that gene
      environment correlations might explain the observed genetic association between
      life events and wellbeing. Inheriting propensity for positive traits might cause
      you to seek environments that lead to positive life events and avoid environments
      which make negative life events more likely.

PMID- 28508959
TI  - Surgical treatment of patellar instability: clinical and radiological outcome
      after medial patellofemoral ligament reconstruction and tibial tuberosity
      medialisation.
AB  - INTRODUCTION: The aim of this retrospective study was to analyse clinical and
      radiological outcome after medial patellofemoral ligament reconstruction (MPFLR)
      and tibial tuberosity medialisation (TTM) in patients with recurrent patellar
      instability. MATERIALS AND METHODS: Thirty-five patients were included between
      2008 and 2012. According to defined criteria such as tibial tuberosity-trochlear
      groove (TTTG) distance, hyperpression on the lateral patella facet and lateral
      retropatellar cartilage damage either MPFLR (group A) or TTM (group B) was
      performed: 18 patients underwent TTM, the other 17 patients underwent MPFLR. At a
      mean of 25.4 +/- 9.7 (group A) and 35.2 +/- 17.6 months (group B) patients were
      clinically and radiologically reviewed. Validated knee scores such as Kujala,
      Lysholm and Tegner score were evaluated. RESULTS: In both groups one patient
      reported of a non-traumatic patellar redislocation. Patients who underwent MPFLR
      (group A) had less pain postoperatively during activity according to the Visual
      Analogue Scale (group A: 2.0 +/- 2.1 points, group B: 3.9 +/- 2.3 points).
      Retropatellar cartilage damage increased in group B from grade 1 (range: 1-3)
      preoperatively to grade 2 (range 1-3) postoperatively (p > 0.05). All other
      clinically evaluated items, as well as the applied knee scoring systems,
      indicated no significant difference (p > 0.05) and displayed good to excellent
      results. CONCLUSIONS: MPFLR and TTM leed to good clinical results despite its own
      indications. For this reason-in selected cases-TTM may still be a suitable
      procedure for surgical treatment of patellar instability. However, patients
      treated by TTM (group B) revealed an increased retropatellar cartilage damage as
      well as significantly more pain during activity.

PMID- 28508961
TI  - Bacteremic kidney cyst infection caused by Helicobacter cinaedi.
AB  - Cyst infection is one of the major complications in patients with autosomal
      dominant polycystic kidney disease (ADPKD). The causative pathogen in kidney cyst
      infection frequently goes undetected. Although only one case report of kidney
      cyst infection caused by Helicobacter cinaedi (H. cinaedi) is published in
      English literature, it may be an important pathogen in kidney cyst infection.
      Kidney cyst infection and H. cinaedi infection share the common characteristic of
      tendency to relapse and chronic kidney disease is a major risk factor for H.
      cinaedi infection. Moreover, a long period is required to detect H. cinaedi in
      blood cultures, potentially causing false-negative results. After the
      identification of H. cinaedi, we must carefully select antibiotics and the
      antibiotic treatment period should be extended to prevent recurrence. Here we
      present a case of a 58-year-old male with ADPKD who developed bacteremic kidney
      cyst infection caused by H. cinaedi. He was admitted to our hospital because of
      fever, lower left back pain, vomiting, and feeling of abdominal enlargement. H.
      cinaedi was detected from the blood cultures obtained at admission after 4 days
      of culture. Antibiotics were administered for 8 weeks after confirming negative
      blood cultures. There was no evidence of kidney cyst infection relapse at 3
      months after treatment completion. Nephrologists should regard H. cinaedi as a
      challenging but important pathogen in kidney cyst infection, particularly when
      the causative organism is unknown or kidney cyst infection is recurrent.

PMID- 28508962
TI  - Proteinuria rebound in IgA nephropathy associated with obesity-related
      glomerulopathy.
AB  - IgA nephropathy (IgAN), the most prevalent primary chronic glomerulonephritis
      worldwide, has three major risk factors: hypertension, proteinuria >1 g/day, and
      severe renal lesions. Obesity also portends a poor prognosis. A Japanese boy with
      IgAN showed nephrotic syndrome at presentation. Pathological features resembled
      those of membranoproliferative glomerulonephritis (MPGN), although IgA deposition
      differed from MPGN and IgAN. Combination therapy improved renal lesions, but
      rebound deterioration of proteinuria occurred in this patient, who had marked
      obesity and hypertension. Serial kidney biopsy specimens were compatible with
      obesity-related glomerulopathy (ORG). Rebound proteinuria was apparently
      attributable to ORG rather than relapse and flaring up of IgAN.

PMID- 28508960
TI  - Impairment of pH gradient and membrane potential mediates redox dysfunction in
      the mitochondria of the post-ischemic heart.
AB  - The mitochondrial electrochemical gradient (Deltap), which comprises the pH
      gradient (DeltapH) and the membrane potential (DeltaPsi), is crucial in
      controlling energy transduction. During myocardial ischemia and reperfusion (IR),
      mitochondrial dysfunction mediates superoxide (.O2-) and H2O2 overproduction
      leading to oxidative injury. However, the role of DeltapH and DeltaPsi in post
      ischemic injury is not fully established. Here we studied mitochondria from the
      risk region of rat hearts subjected to 30 min of coronary ligation and 24 h of
      reperfusion in vivo. In the presence of glutamate, malate and ADP, normal
      mitochondria (mitochondria of non-ischemic region, NR) exhibited a heightened
      state 3 oxygen consumption rate (OCR) and reduced .O2- and H2O2 production when
      compared to state 2 conditions. Oligomycin (increases DeltapH by inhibiting ATP
      synthase) increased .O2- and H2O2 production in normal mitochondria, but not
      significantly in the mitochondria of the risk region (IR mitochondria or post
      ischemic mitochondria), indicating that normal mitochondrial .O2- and H2O2
      generation is dependent on DeltapH and that IR impaired the DeltapH of normal
      mitochondria. Conversely, nigericin (dissipates DeltapH) dramatically reduced .O2
      and H2O2 generation by normal mitochondria under state 4 conditions, and this
      nigericin quenching effect was less pronounced in IR mitochondria. Nigericin also
      increased mitochondrial OCR, and predisposed normal mitochondria to a more
      oxidized redox status assessed by increased oxidation of cyclic hydroxylamine, CM
      H. IR mitochondria, although more oxidized than normal mitochondria, were not
      responsive to nigericin-induced CM-H oxidation, which is consistent with the
      result that IR induced DeltapH impairment in normal mitochondria. Valinomycin, a
      K+ ionophore used to dissipate DeltaPsi, drastically diminished .O2- and H2O2
      generation by normal mitochondria, but less pronounced effect on IR mitochondria
      under state 4 conditions, indicating that DeltaPsi also contributed to .O2-
      generation by normal mitochondria and that IR mediated DeltaPsi impairment.
      However, there was no significant difference in valinomycin-induced CM-H
      oxidation between normal and IR mitochondria. In conclusion, under normal
      conditions the proton backpressure imposed by DeltapH restricts electron flow,
      controls a limited amount of .O2- generation, and results in a more reduced
      myocardium; however, IR causes DeltapH impairment and prompts a more oxidized
      myocardium.

PMID- 28508963
TI  - Hemodiafiltration for hepatic encephalopathy induced by Budd-Chiari syndrome in a
      patient with end-stage kidney disease.
AB  - A 36-year-old woman who was undergoing dialysis for end-stage kidney disease
      (ESKD) was admitted to our hospital with consciousness disorder. She was
      diagnosed with Budd-Chiari syndrome due to antiphospholipid syndrome at the age
      of 28 years. Her kidney function and leg edema gradually deteriorated. After
      initiation of hemodialysis (HD), transient loss of consciousness due to hepatic
      encephalopathy during HD treatment occurred frequently. Her kidney replacement
      therapy was changed to online hemodiafiltration (HDF), which dramatically
      improved her hepatic coma. Compared with HD, HDF contributed to the increase in
      Fischer's ratio and decrease in tryptophan level, which has a high protein-bound
      property. This case suggests that HDF may be beneficial for hepatic
      encephalopathy in ESKD patients by modulating the amino acid profile.

PMID- 28508964
TI  - TMEM67 mutations found in a case of Joubert syndrome with renal hypodysplasia.
AB  - Joubert syndrome is a rare inherited cerebellar ataxia with the dysgenesis of the
      cerebellar vermis, called the molar tooth sign. The combination of a large number
      of causative genes, more than 27, and the various clinical features involving
      multiple organs has established many genotypic-phenotypic correlations in Joubert
      syndrome. TMEM67 is one of the genes that are relatively well established as
      contributing to Joubert syndrome with liver involvement. Here, we report a 2
      month-old boy who was initially treated for urinary tract infection, which
      further led to the diagnosis of Joubert syndrome accompanied by renal
      hypodysplasia with two different mutations: c.2522A>C and c.1065 + 4Adel in
      TMEM67.

PMID- 28508965
TI  - Cinacalcet in hyperparathyroidism management after pediatric renal
      transplantation.
AB  - Secondary hyperparathyroidism is often associated with end stage renal disease;
      even after renal transplantation, hyperparathyroidism may persist, and is
      responsible for hypercalcemia, hypophosphatemia and elevated parathyroid hormone
      (iPTH) levels. Parathyroid hyperplasia is frequently associated with persistent
      hyperparathyroidism, and may require a surgical treatment. Here, we report
      hyperparathyroidism along with parathyroid hyperplasia in a 7-year-old child,
      which persisted after renal transplant. Calcitonin and pamidronate failed to
      decrease serum calcium levels; clodronate was also inefficient. Cinacalcet
      therapy normalized serum calcium and phosphorus levels, and decreased iPTH levels
      in 3 months; a severe parathyroid hyperplasia was also corrected under
      calcimimetic therapy. In conclusion, we report in a child that hypercalcemia
      associated with secondary hyperparathyroidism can be corrected with cinacalcet
      after pediatric renal transplantation. We also show that parathyroid hyperplasia
      can regress under calcimimetic therapy in a transplanted child, making surgery
      unnecessary.

PMID- 28508966
TI  - Recurrent purple urine bag syndrome presenting with full spectrum of disease
      severity: case report and review of literature.
AB  - Purple urine bag syndrome (PUBS) is a unique phenomenon characterized by purple
      discoloration of the urinary catheter bag and tubing following urinary
      catheterization lasting for hours to days. The purple discoloration is a mixture
      of indirubin dissolved in plastic with indigo on its surface. PUBS is most
      commonly associated with urinary tract infection (UTI) caused by bacteria with
      indoxyl phosphatase/sulfatase activity. It occurs predominantly in chronically
      catheterized, constipated elderly female patients. It usually appears to be
      asymptomatic and harmless, but rarely it can present as a severe illness. We
      report on a 29-year-old female with urinary ileal diversion presenting with
      multiple episodes of PUBS each with an asymptomatic state of varying severity,
      symptomatic UTI and severe sepsis requiring intensive care. To our knowledge,
      this is the first report where a single young patient had recurrent PUBS which
      presented with a full spectrum of disease severity at different occasions.

PMID- 28508967
TI  - A case of xanthinuria type I with a novel mutation in xanthine dehydrogenase.
AB  - Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal
      recessive disorder that is characterized by impaired renal tubular uric acid
      transport, or by xanthinuria, a rare autosomal recessive disorder caused by a
      deficiency of xanthine dehydrogenase (XDH; xanthinuria type I) or by a deficiency
      of both XDH and aldehyde oxidase (xanthinuria type II). In contrast to renal
      hypouricemia, which sometimes leads to exercise-induced acute kidney injury
      (EIAKI), xanthinuria has not been associated with this disorder. We report here a
      case of xanthinuria type I due to a compound heterozygous mutation. A 46-year-old
      woman was found to have undetectable plasma and urinary levels of uric acid. She
      had no symptoms and no history of EIAKI. Xanthinuria type I was diagnosed
      following the allopurinol loading test. Mutation analysis revealed a compound
      heterozygous mutation [c.305A>G (p.Gln102Arg) and c.2567delC (p.Thr856Lysfs*73)]
      in the XDH gene. Of these two mutations, the former is novel. The patient did not
      exhibit EIAKI. However, because xanthinuria is a rare disease, the identification
      of additional cases is necessary to determine whether this disease is complicated
      with EIAKI.

PMID- 28508968
TI  - Dialysis disequilibrium leading to posterior reversible encephalopathy syndrome
      in chronic renal failure.
AB  - Dialysis disequilibrium syndrome is a neurological adverse effect of acute
      hemodialysis in advanced uremic patients. Dialysis disequilibrium has a wide
      spectrum of clinical manifestations starting from subtle uneasiness, confusion,
      to florid and complex life threatening neurological deficit. In this case study,
      we present a patient who developed sudden cortical blindness following
      hemodialysis due to posterior reversible encephalopathy, which is a rare
      presentation of dialysis disequilibrium syndrome.

PMID- 28508969
TI  - Five-year follow-up of a case of lipoprotein glomerulopathy with APOE Kyoto
      mutation.
AB  - We report the case of a 34-year-old Japanese male with lipoprotein glomerulopathy
      (LPG). Renal biopsy showed LPG, and followed by a genetic analysis revealed a
      mutation in apolipoprotein E gene (APOE Kyoto; Arg25Cys). We started treatment
      with probucol, bezafibrate, losartan, and allopurinol. Urinary protein decreased
      in response to treatment but has remained at about 1.27 +/- 0.71 g/gCr, and a
      repeat biopsy which was performed 1 year after the first biopsy showed no clear
      evidence of pathological remission and complication of other glomerular disease.
      After 5 years of follow-up after the start of treatment, renal function has
      almost maintained without apparent deterioration. Interestingly, the course of
      the urinary protein level closely paralleled his triglyceride and cholesterol
      levels in a long-term. This observation suggests the importance of tight control
      of lipid profiles as a means of renoprotection in LPG patient.

PMID- 28508970
TI  - Glomerulopathy with distinctive fibrillar deposits but lacking glomerular
      deposition of type III collagen.
AB  - A 62-year-old woman with nephrotic syndrome underwent a renal biopsy. Under light
      microscopy, the biopsy findings included lobulation and enlargement of glomeruli,
      occasional thickening of glomerular capillary walls, and narrowing of the
      capillary lumen by swollen endothelial cells. Congo red staining was negative for
      amyloid. No significant intraglomerular fibrin deposition was found by
      phosphotungstic acid hematoxylin staining. Immunofluorescence microscopy showed
      no deposition of immunoglobulin G, A, or M; no kappa or lambda light chains; and
      no C3 or C1q. Electron microscopy revealed distinctive subendothelial and
      mesangial fibrillar deposits, mesangial cell interposition, and swelling and
      vacuolization of endothelial cells resulting in capillary lumen narrowing.
      Although some curvilinear fibrillar deposits mimicked the bundles of type III
      collagen fibers seen in collagenofibrotic glomerulopathy, neither glomerular
      deposition of type III collagen nor elevation of serum procollagen III peptide
      was noted. This glomerulopathy does not fulfill any known disease entities with
      non-amyloid non-immunoglobulin-derived organized glomerular deposits.

PMID- 28508971
TI  - Short-term outcome and quality of life in kidney transplant recipient with
      monoclonal gammopathy.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is the common pre
      malignant B cell disorders with a general prevalence of 3-5 % at age over 50.
      Because of the potential malignant transformation and immune insufficiency, pre
      transplant MGUS recipient should be carefully followed after allograft
      transplantation. The post-transplant prognosis and quality of life (QOL) in
      patient with MGUS have not yet been fully determined. The aim of this study is to
      evaluate function and pathology of the renal allograft and self-assessment QOL
      changes during 2 years after transplantation in our case of MGUS-bearing
      recipient. We here studied the clinical course and QOL improvement before and 20
      months after transplant in a 56-year-old woman, who had pre-existing MGUS and
      underwent living donor kidney transplantation. After the renal allograft
      transplant, the patients maintained normal GFR and had neither acute rejections
      nor histologic evidence of renal injuries related to the monoclonal gammopathy on
      the protocol biopsy of 1 year post-transplant. During further 20 months follow
      up, the pre-transplant MGUS remained uneventful without any hematologic
      abnormalities and other medical complications, i.e., infection. Evaluation of QOL
      using a self-assessment questionnaire showed significant improvement for physical
      and mental items on both 6 and 18 months post-transplant. The renal transplant
      thus successfully provided a greater satisfaction for the recipient on both
      physical and mental health aspects. Our observations suggest that renal
      transplantation is beneficial even in those who had pre-existing MGUS if managed
      and followed carefully, which ultimately could significantly improve the patient
      QOL.

PMID- 28508972
TI  - Development of intracerebral hemorrhage in the short-term clinical course of a
      patient with microscopic polyangiitis without neurological symptoms at diagnosis:
      an autopsy case.
AB  - A 77-year-old man with high-grade fever, progressive renal dysfunction, high
      serum level of C-reactive protein and positive serum myeloperoxidase anti
      neutrophil cytoplasmic antibody (MPO-ANCA) was diagnosed with microscopic
      polyangiitis with rapidly progressive glomerulonephritis, and remission induction
      treatment with glucocorticoids and intravenous cyclophosphamide was initiated.
      Although his general condition improved in a short time, intracerebral hemorrhage
      occurred 12 days after the initiation of treatment and emergent hematoma
      evacuation was performed. However, he passed away on day 14. Surprisingly, even
      though no clinical findings for any organs except for renal involvement was
      detected before his death, autopsy revealed necrotizing vasculitis affecting
      various systemic organs including kidney, pancreas, liver, myocardium in
      ventricle, adipose tissue of the left adrenal gland, small intestine,
      gallbladder, bronchus, prostate, testis and spleen. It is difficult to detect
      widespread vasculitis without clinical symptoms and signs in patients with ANCA
      associated vasculitis. A whole body assessment tool is necessary to detect
      unexpected vital organ damage, including cerebral vessels.

PMID- 28508973
TI  - Phlegmasia cerulean dolens: complication of femoral vein catheterization.
AB  - There are three less frequent manifestations of acute massive venous thrombosis
      and obstruction of the venous drainage of an extremity. They are phlegmasia alba
      dolens, phlegmasia cerulean dolens (PCD), and venous gangrene. The term PCD
      differentiates ischemia-associated massive venous thrombosis from phlegmasia alba
      dolens, which describes fulminant venous thrombosis without ischemia. We present
      a 55-year-old hypertensive, who presented with paedal oedema and breathlessness
      at rest. About a month prior to this admission, she suffered dislocation of left
      patella. She was treated with a plaster cast and immobilization for 3 weeks. Her
      serum creatinine was 8.8 mg/dL. She was initiated on haemodialysis via two single
      lumen catheters placed in left femoral vein. The femoral vein catheters were
      removed after third session of haemodialysis. On fourth day, the patient
      complained pain and blue discolouration of left toes. On examination, the left
      lower limb was swollen, discoloured, and cold with blebs up to upper one-third of
      left leg. The left dorsalis pedis and posterior tibial arteries were not
      palpable. A Doppler of veins of lower limb revealed, thrombosis of deep, and
      superficial venous system of left lower limb. As there was no response to
      anticoagulation below, knee amputation was performed.

PMID- 28508974
TI  - Pauci-immune crescentic glomerulonephritis associated with use of trimethoprim
      sulfamethoxazole.
AB  - Drug-induced pauci-immune crescentic glomerulonephritis has been described with
      several agents, including propylthiouracil, minocycline, D-penicillamine, and
      hydralazine. We present the case of a 60-year-old man who presented with rapidly
      progressive glomerulonephritis in the setting of recent use of trimethoprim
      sulfamethoxazole complicated by the development of the Stevens-Johnson syndrome,
      and was found to have biopsy-proven pauci-immune crescentic glomerulonephritis
      and undetectable anti-neutrophilic cytoplasmic antibodies. We review the existing
      literature on the potential association between sulfonamides and hypersensitivity
      polyangiitis.

PMID- 28508975
TI  - A case of acquired lecithin:cholesterol acyltransferase deficiency with
      sarcoidosis that remitted spontaneously.
AB  - Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare
      inherited disorder that causes an extremely low high-density lipoprotein
      cholesterol concentration in serum. Recently, acquired LCAT deficiency caused by
      IgG antibodies to LCAT, without any LCAT gene mutation, was reported. Here we
      describe a case of acquired LCAT deficiency occurring in association with
      sarcoidosis. The patient was a Japanese female aged 70 years, had no mutation in
      the LCAT gene exon sequence, but had an LCAT inhibitor factor in her serum,
      detected using lipoprotein-deficient serum. She was diagnosed with acquired LCAT
      deficiency. Her abnormalities of serum lipoproteins improved spontaneously during
      three and a half years. Because they require different treatment strategies,
      distinction between familial lecithin:cholesterol acyltransferase deficiency
      (FLD) and acquired LCAT deficiency by gene sequencing is warranted, especially in
      cases without corneal clouding.

PMID- 28508976
TI  - Idiopathic collapsing focal segmental glomerulosclerosis in an 81-year-old
      Japanese woman: a case report and review of the literature.
AB  - Focal segmental glomerulosclerosis (FSGS) is classified into five variants, with
      the collapsing variant being the most rare. Collapsing FSGS is characterized by a
      black racial predominance and is often associated with human immunodeficiency
      virus-associated nephropathy. However, the number of idiopathic cases is
      increasing and the presentation of non-black patients becoming more routine. Our
      analysis of 15 previous reports investigating FSGS variants shows that the
      collapsing variant accounts for 10.6 % of FSGS cases and its average age of onset
      is 32 years old. The current case is one of the oldest cases of idiopathic
      collapsing FSGS identified, being an 81-year-old Japanese woman. She presented
      with severe renal insufficiency (serum creatinine 7.9 mg/dL, albumin 1.5 g/dL)
      and so underwent hemodialysis immediately. Urinalysis demonstrated 3+ proteinuria
      and 3+ hematuria and the serological work up was all negative. Renal biopsy
      showed wrinkling of capillary walls with collapse lumens in every glomerulus,
      without endothelial tubuloreticular inclusions. Combined treatment with steroids,
      cyclosporine and low-density lipoprotein apheresis increased urine output
      slightly but she was unable to withdraw from hemodialysis and died 3 months
      later. This variant is reported to have the highest rate of progression to end
      stage renal disease, regardless of the therapeutic intervention. However, there
      are also examples of cases with partial or complete remission in the literature.
      Progressive cases, like the current case, seem to be difficult to induce
      remission in, so it is important to diagnose idiopathic collapsing FSGS at an
      early stage by performing a renal biopsy, even in elderly patients.

PMID- 28508977
TI  - Thrombotic microangiopathy caused by interferon beta-1b for multiple sclerosis: a
      case report.
AB  - A 41-year-old man with a history of multiple sclerosis (MS) developed thrombotic
      microangiopathy after taking interferon beta-1b for 10 years. Although the
      relapse of his MS was well controlled under normal blood pressure, he had
      persistent nausea, anorexia, gait disturbance and visual disorder 1 month before
      admission. He showed lethargy and high blood pressure (180/102 mmHg). Laboratory
      test results revealed anemia and thrombocytopenia, elevated LDH and renal
      dysfunction. Urinary dipstick showed a 2+ result for proteinuria and 3+ for
      hematuria. Schizocyte were present and haptoglobin decreased, and we diagnosed
      him with possible thrombotic microangiopathy (TMA). Magnetic resonance image
      indicated posterior reversible encephalopathy syndrome (PRES), which could be
      accelerated by TMA. After discontinuing interferon beta-1b, high dose intravenous
      methylpredonisolone, anti-hypertension therapy and plasma exchange was started.
      Because a mild decrease in ADAMTS13 activity and absence of ADAMTS 13 inhibitor
      could not cause thrombotic thrombocytopenic purpura, plasma exchange was stopped.
      The patient's renal function recovered and PRES resolved, and he was discharged
      with slightly decrease of visual acuity. We suggest that his TMA was likely
      caused by interferon beta-1b, resulting in PRES in a patient with multiple
      sclerosis. We report this rare case and also review the literature.

PMID- 28508978
TI  - Acute tumoral calcinosis due to severe hyperphosphatemia in a maintenance
      hemodialysis patient.
AB  - We report the case of a maintenance hemodialysis patient with severe
      hyperphosphatemia (26.6 mg/dL) who developed acute tumoral calcinosis. The
      patient started receiving maintenance hemodialysis after being diagnosed with
      type 2 diabetes mellitus. The patient's phosphate levels suddenly increased. He
      had not taken the prescribed phosphate binders for the past 5 years. He noticed
      swelling of the palmar aspects of his right thumb, which was diagnosed as tumoral
      calcinosis. His serum phosphate level reached 26.6 mg/dL. He started taking
      medication to lower his serum phosphate levels. The patient had a long history of
      eating convenience foods. As food additives in convenience foods could be a major
      source of phosphate, the patient corrected this habit by replacing convenience
      foods with special foods for dialysis patients. His symptoms improved along with
      the decrease in his serum phosphate levels. The main reason for the abrupt
      decrease in phosphate levels could be the correction of his dietary habits.
      Therefore, phosphate levels in processed foods should be carefully considered in
      dialysis patients.

PMID- 28508979
TI  - Urinothorax in a child secondary to obstructive renal stone in a solitary
      functioning kidney: a case report.
AB  - Urinothorax or presence of urine in pleural cavity is a highly unusual cause of
      pleural effusion. It is most commonly secondary to genitourinary trauma and
      obstructive uropathy. We here by present a case of urinothorax secondary to renal
      stone disease in a 5-year-old child with a solitary functioning kidney.

PMID- 28508980
TI  - An adult case of severe steroid-resistant Henoch-Schonlein purpura nephritis
      treated with intravenous cyclophosphamide and tonsillectomy.
AB  - A previously healthy 37-year-old Canadian man living in Japan visited a hospital
      in Thailand while traveling because of edematous legs, purpura, arthralgia,
      bloody stool, and fever after an insect bite. Henoch-Schonlein purpura (HSP) was
      suspected. His creatinine level was 5.2 mg/dL. He was treated with oral
      prednisolone (PSL) and oral cyclophosphamide (CPA); after treatment, his
      creatinine level improved to 2.4 mg/dL. Upon returning to Japan, he was admitted
      to the National Center for Global Health and Medicine Hospital in Tokyo. A kidney
      biopsy was performed, and HSP nephritis (HSPN) was diagnosed. Renal dysfunction
      and proteinuria persisted despite 4 administrations of steroid-pulse therapy and
      3 sessions of plasma exchange. Finally, he was treated with intravenous
      cyclophosphamide (IVCY). His creatinine level and proteinuria markedly improved.
      His microscopic hematuria disappeared after he underwent tonsillectomy. There
      have been only a few case reports describing patients with adult-onset HSPN
      necessitating IVCY. We present here a rare case of steroid-resistant HSPN treated
      with IVCY and tonsillectomy, with reference to some recent findings.

PMID- 28508981
TI  - Partial remission by cyclosporine monotherapy in a patient with membranous
      nephropathy superimposed diabetic nephropathy.
AB  - It has been noted that cyclosporine A (CsA) is an effective drug for membranous
      nephropathy (MN). Diabetes is a common disease that sometimes causes nephrotic
      syndrome. We report the case of an 89-year-old woman with type 2 diabetes
      mellitus who exhibited nephrotic syndrome. Examination of a renal biopsy
      indicated MN and she was prescribed CsA as monotherapy. Her edema subsided and
      she achieved partial remission. This is the first report of a patient in diabetic
      condition with MN having achieved partial remission after CsA monotherapy without
      steroid therapy. The use of steroid in patients with diabetes may worsen their
      diabetic condition, especially if they are of very advanced age. CsA monotherapy
      may be useful for diabetic patients with MN.

PMID- 28508982
TI  - Renal hemorrhage caused by acquired inhibitors to coagulation factors VIII and V
      in a hemodialysis patient.
AB  - Acquired coagulation factor deficiency is a rare bleeding disorder caused by the
      inhibitors to coagulation factors. We report a case of an elderly hemodialysis
      patient who presented with the intermittent hematuria and anemia, associated with
      the prolonged activated partial thromboplastin time and prothrombin time.
      Laboratory examination revealed undetectable factor VIII activity, decreased
      factor V activity, and the presence of inhibitors to these coagulation factors.
      The patient was diagnosed to have inhibitors to coagulation factors VIII and V
      simultaneously. In addition, hematuria was found to be caused by the right renal
      hemorrhage. Renal extravasation was treated by transcatheter arterial
      embolization. Oral prednisolone successfully eradicated the inhibitors. The
      present case highlights the importance to consider acquired coagulation factor
      inhibitors for bleeding symptoms, because they are sometimes life-threatening.

PMID- 28508983
TI  - Effect of tolvaptan in a patient with autosomal dominant polycystic kidney
      disease after living donor liver transplantation.
AB  - Recently, a large randomized placebo-controlled trial indicated a beneficial
      effect of tolvaptan on the progression of autosomal dominant polycystic kidney
      disease (ADPKD) with near-normal kidney function. Meanwhile, the evidence of
      tolvaptan's efficacy in ADPKD with severe renal insufficiency was limited and
      higher frequency of liver enzyme elevations were observed in patients taking
      tolvaptan. Liver transplantation (LT) is the only curative treatment for patients
      with severe polycystic liver disease associated with ADPKD, but considering that
      liver injuries should be avoided particularly in patients who underwent LT, we
      must be careful to start tolvaptan in post-LT ADPKD patients. We describe the
      case of a patient who had developed severe renal insufficiency after living donor
      LT, for whom tolvaptan therapy showed marked reduction of total kidney volume and
      maintenance of renal function without any serious adverse events. This is the
      first report to show the beneficial effect and safety of tolvaptan, in a post-LT
      ADPKD patient with severe renal insufficiency, and hopefully will help broaden
      the spectrum of patients who will benefit from tolvaptan.

PMID- 28508985
TI  - Light chain Fanconi syndrome in a patient with acute myeloid leukemia and
      monoclonal gammopathy of undetermined significance.
AB  - Proximal tubules are a target for paraproteinemic diseases. Cast nephropathy,
      light chain deposition diseases, and amyloidosis are frequently encountered in
      patients with multiple myeloma. Rarely, a subset of patients develop light chain
      Fanconi syndrome (LCFS). LCFS has been reported with multiple myeloma, monoclonal
      gammopathy of renal significance (MGRS), chronic lymphocytic leukemia,
      Waldenstrom's macroglobulinemia and diffuse large B-cell lymphoma. No cases have
      been described with other hematologic malignancies. We report the first case of
      lambda LCFS in a patient with both acute myeloid leukemia (AML) and monoclonal
      gammopathy of undetermined significance (MGUS).

PMID- 28508986
TI  - List of referees.

PMID- 28508984
TI  - Successful treatment of myeloma cast nephropathy using bortezomib-based
      chemotherapy plus selective plasma exchange.
AB  - Myeloma cast nephropathy is a major complication of multiple myeloma. Recent
      evidence has demonstrated that the earlier induction of bortezomib-based
      chemotherapy with plasma exchange (PE) provides better results for kidney
      function and patient survival. Due to its non-selectivity, PE with albumin
      replacement carries the risk of fibrinogen loss, leading to bleeding. We herein
      report a case of successful treatment of myeloma cast nephropathy using
      bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20
      year history of type II diabetes mellitus was admitted to our hospital for the
      evaluation of hypercalcemia, severe kidney dysfunction, and anemia. Subsequent
      bone marrow evaluation and renal biopsy revealed that she had multiple myeloma
      (IgG-kappa) and myeloma cast nephropathy. Ten days after admission, bortezomib
      based chemotherapy with selective PE achieved rapid and thorough free light-chain
      (FLC) reduction; within a month, her kidney function had been recovered
      (creatinine level, 1.2 mg/dl). Her serum fibrinogen level was not reduced, and no
      bleeding complication occurred. Five months later, autologous hematopoietic stem
      cell transplantation was performed successfully, and the patient's kidney
      function was stable (creatinine level, 1.1 mg/dl) thereafter. This case report
      demonstrates the importance of early induction therapy with bortezomib-based
      chemotherapy and PE in a patient with myeloma cast nephropathy, which is
      especially applicable in patients aged <65 years. In addition, it shows that
      selective PE is a safe and effective method of FLC removal.

PMID- 28508987
TI  - Transmission of H6N2 wild bird-origin influenza A virus among multiple bird
      species in a stacked-cage setting.
AB  - Live bird markets are common in certain regions of the U.S. and in other regions
      of the world. We experimentally tested the ability of a wild bird influenza A
      virus to transmit from index animals to naive animals at varying animal densities
      in stacked cages in a simulated live bird market. Two and six mallards, five and
      twelve quail, and six and nine pheasants were used in the low-density and high
      density stacks of cages, respectively. Transmission did not occur in the high
      density stack of cages likely due to the short duration and relatively low levels
      of shedding, a dominance of oral shedding, and the lack of transmission to other
      mallards in the index cage. In the low-density stack of cages, transmission
      occurred among all species tested, but not among all birds present. Oral and
      cloacal shedding was detected in waterfowl but only oral shedding was identified
      in the gallinaceous birds tested. Overall, transmission was patchy among the
      stacked cages, thereby suggesting that chance was involved in the deposition of
      shed virus in key locations (e.g., food or water bowls), which facilitated
      transmission to some birds.

PMID- 28508988
TI  - Guillain-Barre syndrome variant with facial diplegia and paresthesias after
      reactivation of varicella zoster virus.

PMID- 28508989
TI  - Evaluation of inner retinal layers with optic coherence tomography in vigabatrin
      exposed patients.
AB  - In order to reveal the underlying retinal pathology leading to dysfunction in
      vigabatrin-exposed patients, we aimed to evaluate the inner retinal layers
      encompassing ganglion cell complex (GCC) layer and inner plexiform layer with new
      generation optic coherence tomography (OCT). Fourteen patients with epilepsy and
      exposure to vigabatrin and 12 clinically normal individuals, constituting the
      control group, were included. Retinal images were obtained using spectral-domain
      OCT (Optovue RTVue Fourier domain). Nasal and superior quadrants of retinal nerve
      fiber layer (RNFL) were found to be significantly lower in the patient group
      compared to the controls (p < 0.01). No significant difference was shown in the
      thickness of GCC layer (p > 0.05). Foveal thickness was significantly higher in
      the patient group (p: 0.006), but no significant difference was found in
      perifoveal and parafoveal regions between groups (p > 0.05). The thickness of
      RNFL was found to be lower in vigabatrin-exposed patients without any reduction
      in GCC layer in the macular region. However, foveal thickness was found to be
      significantly higher compared to perifoveal and parafoveal macular regions in
      vigabatrin-exposed patients. In conclusion, OCT revealed reduced thickness of
      RNFL without any reduction in ganglion cell layer in our study. The objective
      quantitative assessment of OCT is a practical noninvasive method and it can have
      role in future monitoring of these patients.

PMID- 28508991
TI  - Digital stethoscopes compared to standard auscultation for detecting abnormal
      paediatric breath sounds.
AB  - : Our study aimed to objectively describe the audiological characteristics of
      wheeze and crackles in children by using digital stethoscope (DS) auscultation,
      as well as assess concordance between standard auscultation and two different DS
      devices in their ability to detect pathological breath sounds. Twenty children
      were auscultated by a paediatric consultant doctor and digitally recorded using
      the LittmanTM 3200 Digital Electronic Stethoscope and a ClinicloudTM DS with
      smart device. Using spectrographic analysis, we found those with clinically
      described wheeze had prominent periodic waveform segments spanning expiration for
      a period of 0.03-1.2 s at frequencies of 100-1050 Hz, and occasionally spanning
      shorter inspiratory segments; paediatric crackles were brief discontinuous sounds
      with a distinguishing waveform. There was moderate concordance with respect to
      wheeze detection between digital and standard binaural stethoscopes, and 100%
      concordance for crackle detection. Importantly, DS devices were more sensitive
      than clinician auscultation in detecting wheeze in our study. CONCLUSION:
      Objective definition of audio characteristics of abnormal paediatric breath
      sounds was achieved using DS technology. We demonstrated superiority of our DS
      method compared to traditional auscultation for detection of wheeze. What is
      Known: * The audiological characteristics of abnormal breath sounds have been
      well-described in adult populations but not in children. * Inter-observer
      agreement for detection of pathological breath sounds using standard auscultation
      has been shown to be poor, but the clinical value of now easily available digital
      stethoscopes has not been sufficiently examined. What is New: * Digital
      stethoscopes can objectively define the nature of pathological breath sounds such
      as wheeze and crackles in children. * Paediatric wheeze was better detected by
      digital stethoscopes than by standard auscultation performed by an expert
      paediatric clinician.

PMID- 28508992
TI  - Palivizumab prophylaxis in infants with cystic fibrosis does not delay first
      isolation of Pseudomonas aeruginosa or Staphylococcus aureus.
AB  - : Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF)
      lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa)
      acquisition, which is of particular importance in the youngest patients. We aimed
      to determine the effectiveness of PVZ on microbiological outcomes in young
      children with CF. We conducted a retrospective case-control study to compare
      these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not
      (PVZ-; n = 140). One case was matched with at least three same-gender controls
      born the same year and month. Median (range) age at first Pa isolation was not
      statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2
      33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4
      [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa
      isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ-
      41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the
      PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not
      significantly differ between groups. CONCLUSION: Systematic PVZ use did not delay
      key pathogen acquisition in young children with CF. What is known: * Palivizumab
      is the only available monoclonal antibody against respiratory syncytial virus
      infection. * Whether or not it is useful in infants with cystic fibrosis remains
      controversial. What is new: * Palivizumab does not delay key pathogens
      (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children
      with cystic fibrosis. * Palivizumab does not reduce healthcare consumption or
      improve growth during the first 3 years of life of young children with cystic
      fibrosis.

PMID- 28508990
TI  - Adolescents with congenital heart disease: their opinions about the preparation
      for transfer to adult care.
AB  - : The aim of the study was to explore what adolescents with congenital heart
      disease (CHD) view as important in the preparation for the transfer to adult
      care. We performed interviews in four focus groups with adolescents (14-18 years
      old) at four university hospitals in Sweden. Data was analysed using qualitative
      content analysis. The analysis revealed one main category; Becoming a manager of
      the condition and four subcategories; Sufficient knowledge about the health, Be a
      participant in the care, Parental support, and Communicate with others about the
      health. The adolescents' ages differentiated the discussion in the groups. The
      older adolescents seemed to have more interest in transition planning,
      information and transfer. The younger described more frustrations about
      communication and handling the disease. CONCLUSION: To become a manager of the
      CHD in daily life, the adolescents want disease specific knowledge, which should
      be communicated in a developmentally appropriate way. Adolescents want to
      participate and be involved in the transition process. They need support and
      guidance in how to communicate their CHD. Parental support is fundamental but it
      change over time. Moreover, peer-support is becoming more significant during the
      transition process. What is Known: * Transition during adolescence and transfer
      to adult care for adolescents with CHD is complex, and there is a shift in roles.
      * Adolescents often have poor knowledge and understanding about their heart
      condition and the consequences. What is New: * Adolescents call for disease
      specific information regarding health issues of importance for them in daily
      life. * Communicating the disease with other is a challenge- peer support from
      other adolescents with CHD could be a facilitator.

PMID- 28508993
TI  - 14,15-EET Suppresses Neuronal Apoptosis in Ischemia-Reperfusion Through the
      Mitochondrial Pathway.
AB  - Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an
      important pathological process in cerebral ischemia-reperfusion injury. 14,15
      EET, an intermediate metabolite of arachidonic acid, can promote cell survival
      during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway
      is involved this survival mechanism is not fully understood. In this study, we
      observed that infarct size in ischemia-reperfusion injury was reduced in sEH gene
      knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF
      nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment
      reduced neuronal apoptosis in the oxygen-glucose deprivation and re-oxygenation
      group in vitro. The mitochondrial apoptosis pathway was also inhibited, as
      evidenced by AIF translocation from the mitochondria to nucleus and the reduction
      in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15
      EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2
      (anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax
      aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the
      reduction of neuronal apoptosis by EET. Our study suggests that 14,15-EET could
      suppress neuronal apoptosis and reduce infarct volume through the mitochondrial
      apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved
      in the neuroprotection against ischemia-reperfusion by 14,15-EET.

PMID- 28508994
TI  - Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model
      of Absence Epilepsy.
AB  - Epilepsy is a common neurological condition characterised by spontaneous
      recurrent seizures. Current anti-epileptic drugs are only effective and tolerated
      in ~70% of patients, leaving a substantial proportion of patients untreated. As
      such, there is a pressing need to develop new therapies. We assessed the anti
      seizure activity of Neural Regeneration Peptide 2945 (NRP 2945) in the GAERS
      model of absence epilepsy. Drug effects on seizures were assessed using two study
      designs. Male adult GAERS were implanted with EEG electrodes to measure seizure
      frequency. The first study compared the effects of acute sc injection of vehicle,
      NRP 10 ug/kg, NRP 20 ug/kg, and controlled against the active comparator
      Valproaic acid (200 mg/kg). In the second study, animals received one of four
      treatments for 4 weeks: vehicle, NRP 60 ug/kg/day, NRP 120 ug/kg/day (delivered
      by continuous infusion) or NRP 20 ug/kg sc injected every second day (e.s.d). In
      the acute study, we found significant (p < 0.01) anti-seizure effects in animals
      treated with NRP2945 (20 ug/kg) and VPA, with NRP2945 slightly more efficacious,
      despite the 70,000 times lower molar dosage. In the chronic study, animals
      receiving 120 ug/kg/day and NRP 20 ug/kg e.s.d had significantly fewer seizures
      (p < 0.001), compared with vehicle. These effects were sustained for at least 10
      days after drug treatment had ceased, indicative of disease-modifying activity.
      We demonstrate sustained anti-seizure effects of NRP2945, a potent small molecule
      peptide which enters the brain and is devoid of adverse effects. Early stage
      first-in-man trials have been initiated for subcutaneously delivered NRP2945
      which is a promising step to providing therapeutic benefits for refractory
      epilepsy patients.

PMID- 28508996
TI  - Hyalinizing Clear Cell Carcinoma of the Bronchus.
AB  - Hyalinizing clear cell carcinoma (HCCC) is an uncommon low-grade minor salivary
      gland neoplasm that usually arises in the head and neck region. We report a 55
      year-old man who presented with a 2.5 cm lung mass that was partially obstructing
      the right bronchus intermedius. The tumor consisted of cords and nests of clear
      and eosinophilic cells in a hyalinized stromal background. The neoplastic cells
      expressed cytokeratin (CK) 7, CK 5/6, high-molecular weight cytokeratin (34BE12),
      p63 and p40, while TTF-1, napsin A, CK20, S100, smooth muscle actin,
      synaptophysin and chromogranin were negative. Mucicarmine stain also was negative
      in the lesional cells. Fluorescence in situ hybridization using break apart
      probes revealed rearrangement of the Ewing Sarcoma Breakpoint Region 1 gene
      locus. The morphologic, immunophenotypic and cytogenetic findings confirmed the
      diagnosis of HCCC, most likely of bronchial submucosal gland origin. To our
      knowledge, only two other reports of primary pulmonary HCCC are available in
      English literature.

PMID- 28508998
TI  - ?

PMID- 28508999
TI  - ?

PMID- 28508997
TI  - Fibromyxoma of the Jaw: Case Report and Review of the Literature.
AB  - We report a case of fibromyxoma of the mandible, a rare benign odontogenic tumor.
      Our patient presented in the first trimester of pregnancy with a large mass in
      the right body of the mandible exhibiting displacement of teeth and destruction
      of an extensive area of the mandibular bone. The mass was biopsied and diagnosed
      as a fibromyxoma. The large size of the tumor dictated a wide mandibular
      resection. We will review the clinical, radiographic, and histologic features of
      fibromyxoma and discuss its differential diagnoses. In addition, we will provide
      an overview of patient management. Fibromxyoma is a benign gnathic tumor that can
      be locally aggressive. To ensure appropriate treatment, it is important to
      distinguish this neoplasm from other mimickers in which myxoid, spindle
      mesenchymal cell proliferation is prominent.

PMID- 28509000
TI  - ?

PMID- 28509001
TI  - ?

PMID- 28509003
TI  - ?

PMID- 28509004
TI  - ?

PMID- 28509002
TI  - ?

PMID- 28508995
TI  - L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain.
AB  - L-Carnitine functions to transport long chain fatty acyl-CoAs into the
      mitochondria for degradation by beta-oxidation. Treatment with L-carnitine can
      ameliorate metabolic imbalances in many inborn errors of metabolism. In recent
      years there has been considerable interest in the therapeutic potential of L
      carnitine and its acetylated derivative acetyl-L-carnitine (ALCAR) for
      neuroprotection in a number of disorders including hypoxia-ischemia, traumatic
      brain injury, Alzheimer's disease and in conditions leading to central or
      peripheral nervous system injury. There is compelling evidence from preclinical
      studies that L-carnitine and ALCAR can improve energy status, decrease oxidative
      stress and prevent subsequent cell death in models of adult, neonatal and
      pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized
      for energy, used as a precursor for acetylcholine, or incorporated into
      glutamate, glutamine and GABA, or into lipids for myelination and cell growth.
      Administration of ALCAR after brain injury in rat pups improved long-term
      functional outcomes, including memory. Additional studies are needed to better
      explore the potential of L-carnitine and ALCAR for protection of developing brain
      as there is an urgent need for therapies that can improve outcome after neonatal
      and pediatric brain injury.

PMID- 28509006
TI  - ?

PMID- 28509005
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PMID- 28509007
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PMID- 28509008
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PMID- 28509009
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PMID- 28509010
TI  - ?

PMID- 28509012
TI  - [Standardized blood pressure measurement in clinical practice].

PMID- 28509011
TI  - ?

PMID- 28509013
TI  - [Mental disorders and problems in afghan refugees: The clinical perspective].

PMID- 28509014
TI  - ?

PMID- 28509015
TI  - [Injuries due to marine animals].

PMID- 28509017
TI  - [Diving accidents].

PMID- 28509016
TI  - [Diving accidents].

PMID- 28509018
TI  - ?

PMID- 28509019
TI  - ?

PMID- 28509020
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PMID- 28509021
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PMID- 28509022
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PMID- 28509023
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PMID- 28509024
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PMID- 28509025
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PMID- 28509027
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PMID- 28509029
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PMID- 28509030
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PMID- 28509031
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PMID- 28509036
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PMID- 28509035
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PMID- 28509037
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PMID- 28509038
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PMID- 28509039
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PMID- 28509040
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PMID- 28509041
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PMID- 28509042
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PMID- 28509043
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PMID- 28509045
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PMID- 28509046
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PMID- 28509044
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PMID- 28509048
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PMID- 28509047
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PMID- 28509049
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PMID- 28509050
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PMID- 28509051
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PMID- 28509052
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PMID- 28509054
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PMID- 28509055
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PMID- 28509056
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PMID- 28509057
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PMID- 28509058
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PMID- 28509059
TI  - ?

PMID- 28509060
TI  - [Management of benign prostatic hyperplasia (BPH)].

PMID- 28509061
TI  - Cardiomyopathy mimicking left ventricular noncompaction in a patient with lupus
      nephritis.
AB  - A 37-year-old female patient was admitted with exertional dyspnea. Her serum
      creatinine was 2.4 mg/dL and anti-nuclear antibody was positive in a titer of
      1/320. Renal biopsy revealed diffuse proliferative lupus nephritis.
      Echocardiography and cardiac magnetic resonance (MR) imaging showed increased
      apical trabeculations compatible with left ventricular noncompaction (LVNC),
      which is a rare genetic cardiomyopathy. The patient expressed a marked
      improvement in exertional dyspnea after the immune-suppressive treatment for
      systemic lupus erythematosus (SLE). Control echocardiography revealed a
      significant increase of ejection fraction. SLE may cause a kind of cardiomyopathy
      with high resemblance to LVNC. Discrimination of these two similar clinical
      entities is important because SLE-induced cardiomyopathy is potentially
      reversible after the immune-suppressive treatment for SLE.

PMID- 28509062
TI  - True identity of endocapillary proliferation: a case of intravascular large B
      cell lymphoma diagnosed with immunohistochemical study of kidney biopsy and
      literature review.
AB  - A 78-year-old Japanese female presented with low-grade fever, malaise, and
      appetite loss lasting for 1 month. Upper and lower gastrointestinal endoscopy and
      contrast-enhanced whole-body computed tomography (CT) revealed no abnormal
      findings at a referring hospital. She was referred to our hospital because of
      bilateral leg edema and 2.5 g/day proteinuria. Serum creatinine was 0.73 mg/dl
      and the kidneys were not enlarged. Kidney biopsy showed marked endocapillary
      proliferation with mesangiolysis. Soon after the kidney biopsy, her symptoms
      improved spontaneously, along with decreases in lactate dehydrogenase (LDH) from
      503 to 197 IU/l, C-reactive protein (CRP) from 4.47 to 0.66 mg/dl, and soluble
      interleukin-2 receptor (sIL-2R) from 1789 to 1001 U/ml. Thus, she was followed
      carefully as an outpatient. One month later, however, she presented with
      dysarthria and right-sided hemiparesis, and diffusion-weighted brain magnetic
      resonance imaging (MRI) showed multiple high-intensity areas. She also had
      respiratory failure, and lung perfusion scintigraphy showed multiple low blood
      stream areas. Suspecting some endovascular abnormality, we performed
      immunohistochemical staining of the kidney biopsy specimen taken previously to
      find that endocapillary infiltrating cells were CD20-positive B lymphocytes. The
      infiltrating cells were confined to the endocapillary compartment in glomeruli
      and peritubular capillaries. Both clinical and pathological findings led us to
      diagnose intravascular large B cell lymphoma (IVLBCL). Two bone marrow biopsies
      and random skin biopsies were performed, but no abnormality was found. The
      present case demonstrates that clinical course and renal biopsy findings of
      intravascular large B cell lymphoma may mimic other renal conditions and that the
      identification of cell types with immunohistochemical staining may help establish
      an accurate diagnosis.

PMID- 28509063
TI  - Successful treatment with tolvaptan to control blood volume and hyponatremia in a
      chronic kidney disease patient.
AB  - We report a case of successful treatment with tolvaptan (15 mg/day) in a 73-year
      old female patient with chronic kidney disease (CKD) stage 5 due to diabetic
      nephropathy and renal sclerosis for volume control and loop diuretic-induced
      hyponatremia. Her creatinine clearance has remained at 7-10 ml/min for the last 6
      months. She was treated by dietary and drug therapy, namely, antihypertensives
      (nifedipine: 40 mg/day, olmesartan: 20 mg/day) and loop diuretics (azosemide: 40
      120 mg/day), for CKD and concomitant diseases of hypertension and diabetic
      mellitus. She developed loop diuretic-induced hyponatremia (120 mmol/l) by
      increased sodium excretion, but the diuretic was required for the control of
      volume overload. Hence, azosemide was suspended and tolvaptan (15 mg/day) was
      administered. After tolvaptan treatment, the plasma sodium level gradually
      increased to a normal level (135-140 mmol/l) and volume overload was improved.
      Urine volume was maintained at about 1000 ml/day with low sodium excretion (<40
      mmol/day) and increased free water clearance. These results suggest that
      tolvaptan may be effective for volume control and diuretic-induced hyponatremia
      in CKD patients.

PMID- 28509064
TI  - Pasteurella multocida peritonitis associated with a cat in a peritoneal dialysis
      patient using an automated cycler device.
AB  - Pasteurella multocida (P. multocida) is an aerobic Gram-negative coccobacillus,
      which is found as part of the natural oral flora of many animals, including most
      healthy cats and dogs. However, it can cause a variety of infections in humans,
      usually as a result of the patient being bitten or scratched by a cat or dog.
      There have been 22 reported cases of P. multocida peritonitis in patients
      undergoing peritoneal dialysis (PD). Of these, 66.7 % occurred within 12 months
      of the initiation of PD. Only two cases (11.1 %) developed more than 60 months
      after the commencement of PD. We report a case of P. multocida peritonitis
      involving a 45-year-old patient who had been undergoing continuous ambulatory
      peritoneal dialysis (CAPD) for 84 months without a previous history of
      peritonitis, who developed P. multocida peritonitis associated with a domestic
      cat on the very night on which he began using an automated cycler device to
      switch from CAPD to continuous cyclic peritoneal dialysis (CCPD). Patients
      maintained on PD who keep pets such as cats or dogs at home should be educated
      about the risk of developing peritonitis related to their domestic pets, and this
      warning should be repeated when such patients switch from CAPD to CCPD.
      Physicians should consider using empiric therapy to prevent P. multocida in pet
      owning PD patients who present with a history of PD fluid leakage and
      peritonitis, especially in patients who use cycler devices.

PMID- 28509065
TI  - A case report of mediastinal seminoma arising after renal transplantation.
AB  - Recipients of organ transplantation on immunosuppressive medications are at
      increased risk for developing de novo malignancies, including skin cancer,
      Kaposi's sarcoma, in situ carcinomas of the uterine cervix, anogenital cancers,
      renal cell carcinoma, and post-transplant lymphoproliferative disorders (PTLD).
      However, there are few case reports of germ cell tumors after organ
      transplantation. There are some case reports of testicular seminoma, but not
      mediastinal seminoma. This case report is the first description of a mediastinal
      seminoma that developed de novo 28 months after renal transplantation and that
      was initially diagnosed as PTLD. To improve outcomes of organ transplant
      recipients, it is important to report rare cases of malignancies arising while on
      immunosuppressive medications. When we detect mediastinal tumor arising after
      organ transplantation while on immunosuppressive therapy, diseases other than
      PTLD should be considered in the differential diagnosis.

PMID- 28509066
TI  - Cyclophosphamide induced early-onset interstitial lung disease.

PMID- 28509067
TI  - Intracranial calcification in a uremic infant with Wilms' tumor in a solitary
      kidney.
AB  - Wilms' tumor (WT), also called nephroblastoma, is an embryonic neoplasm of the
      developing kidney. A previously healthy Japanese female infant had WT in a single
      kidney without associated congenital malformations. Preoperative chemotherapy was
      started for the preservation of renal tissue and function. Tumor lysis syndrome,
      disseminated intravascular coagulopathy, and acute renal failure were
      accompanying. The infant needed surgical intervention and permanent replacement
      therapy. At the start of emergency hemodialysis, the infant had posterior
      reversible leukoencephalopathy syndrome because of severe hypertension. During
      ongoing peritoneal dialysis, the infant suffered from anemia, dietary and fluid
      restriction, and restriction of time and mobility. Despite alfacalcidol and
      calcium supplementation, the infant had secondary hyperparathyroidism and
      remarkably short stature. After waiting for the completion of chemotherapy, renal
      transplantation from the mother was completed. Successful kidney transplantation
      promptly corrected preexisting metabolic abnormalities causing secondary
      hyperparathyroidism. Subsequently, the infant often complained of headache.
      Computed tomographic scanning revealed calcification in the cerebellum.
      Refractory secondary hyperparathyroidism was inferred as the cause. A well
      functioning graft provided the infant with a greater sense of well-being and
      enabled her to enjoy a lifestyle free of dialysis, although the infant must
      continue taking transplant medications and has retained unresolved issues of
      short stature and ectopic intracranial calcification.

PMID- 28509068
TI  - The combined use of edaravone, diuretics, and nonsteroidal anti-inflammatory
      drugs caused acute kidney injury in an elderly patient with chronic kidney
      disease.
AB  - The purpose of this study was to draw attention to the fact that the combined use
      of edaravone, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) may
      lead to acute kidney injury. This study was a case report of acute kidney injury
      resulting from the combined use of the aforementioned types of drugs. A 77-year
      old male patient with chronic kidney disease (third stage) who was treated with a
      combination of edaravone, diuretics, and NSAIDs showed significantly increased
      blood urea nitrogen and creatinine. Interestingly, the blood urea nitrogen and
      creatinine levels returned to pretreatment levels after the medications were
      stopped. The patient's score on the Naranjo Adverse Drug Reaction Probability
      Scale was a nine, and the score on the Drug Interaction Probability Scale was a
      five. For elderly patients with chronic kidney disease, the combined use of
      edaravone, diuretics, and NSAIDs should be avoided.

PMID- 28509069
TI  - A case of the "cellular variant" of focal segmental glomerulosclerosis with acute
      renal failure that remitted completely with oral steroid administration.
AB  - A 73-year-old man with systemic edema and oliguria, which appeared within several
      days, was referred to our hospital. Urinalysis showed massive proteinuria, and
      the blood examination results indicated nephrotic syndrome. Renal biopsy revealed
      the existence of focal segmental glomerulosclerosis (FSGS), and further
      investigation indicated that the microscopic features were consistent with the
      "cellular variant (CELL)" according to the Columbia Classification. After biopsy,
      40 mg per day of oral prednisolone was administered daily. With steroid therapy,
      the abnormal values of the blood examination and urinalysis gradually reached
      normal, and complete remission was achieved on day 43 after initiating steroid
      administration. Microscopic investigation by follow-up renal re-biopsy revealed
      several sclerosing glomeruli; however, other intact glomeruli had no endothelial
      proliferation, which is a hallmark of CELL. The patient was discharged after
      biopsy and observed as an outpatient, with maintenance of clinical remission.

PMID- 28509071
TI  - Fever associated with severe dialysis-related amyloidosis.
AB  - Dialysis-related amyloidosis (DRA) is one of the most important complications in
      patients on long-term hemodialysis (HD). DRA often affects the osteoarticular
      system; however, little is known about the role of beta2-microglobulin in the
      induction of fever in HD patients. We report a 64-year-old woman on long-term (24
      years) HD who developed polyarthralgia and intermittent fever. Infectious
      diseases, connective tissue diseases, and malignant neoplasm were ruled out.
      Computed tomography and magnetic resonance imaging showed swelling of the soft
      tissues around bilateral shoulder and hip joints, suggestive of amyloid deposits.
      Gallium scintigraphy showed abnormal uptake in the vicinity of several large
      joints. It was presumed that the fever was related to the amyloid joint deposits,
      and the patient was treated with prednisolone and beta2-microglobulin adsorption
      therapy. The treatment resulted in the resolution of fever, relief of arthralgia,
      and normalization of several inflammatory cytokines and C-reactive protein. The
      findings suggest that massive DRA could cause systemic inflammatory response in
      patients on long-term HD.

PMID- 28509072
TI  - Urgent hemodialysis induced an acute gout attack in a patient with multiple
      tophi: report of a rare case.

PMID- 28509070
TI  - A case of (double) ANCA-negative granulomatosis with polyangiitis (Wegener's).
AB  - A 60-year-old man had experienced cough, bloody sputum, and a 38  degrees C fever
      for 1.5 months. He visited an outpatient clinic and received antibiotics and
      nonsteroidal anti-inflammatory drugs. However, because the symptoms continued, he
      visited our hospital. The past medical history included chronic sinusitis,
      hypertension, and diabetes mellitus. A chest x-ray film and computed tomography
      showed multiple pulmonary nodules with cavities. Macrohematuria had developed 3
      days before admission, and renal function had deteriorated (creatinine, 2.45
      mg/dL) in 2 weeks. He was admitted to our hospital because of rapidly progressive
      glomerulonephritis (RPGN) and multiple pulmonary nodules. On admission, the
      clinical diagnosis was suspected to be granulomatosis with polyangiitis
      (Wegener's) (GPA), although tests for proteinase-3 anti-neutrophil cytoplasmic
      antibody (PR3-ANCA) were negative. Antibiotics were administered for 5 days.
      After renal biopsy, methylprednisolone pulse therapy and cyclophosphamide pulse
      therapy were performed. The pathological diagnosis on the basis of the renal
      biopsy was glomerular and interstitial hemorrhage, possibly associated with
      vasculitis. After the treatment, the pulmonary symptoms, multiple pulmonary
      nodules, and severe inflammatory reactions in the peripheral blood were resolved.
      However, renal dysfunction progressed to end-stage renal disease 1 month after
      renal biopsy. Hemodialysis was started, and the steroid therapy was continued.
      During hemodialysis, a second renal biopsy was performed and led to a diagnosis
      of pauci-immune focal segmental crescentic glomerulonephritis. Renal function
      gradually recovered, and hemodialysis was discontinued. This case was (double)
      ANCA-negative GPA which presented prominent glomerular and interstitial
      hemorrhage, may be associated with small vessel vasculitis, but without active
      necrotizing and crescentic glomerular lesions, in the rapidly progressive
      glomerulonephritis.

PMID- 28509073
TI  - Systemic and rapidly progressive light-chain deposition disease initially
      presenting as tubulointerstitial nephritis.
AB  - A 42-year-old woman was admitted to a hospital after first-time detection of
      proteinuria and hematuria during a routine medical check-up. Because her serum
      creatinine level had rapidly increased from 0.9 to 3.2 mg/dl since measurement 3
      months earlier, she was referred to our hospital. Renal biopsy revealed extensive
      tubular atrophy and interstitial fibrosis with mild leukocyte infiltration.
      Glomeruli showed minimal changes, and no immunoglobulin or complement deposition
      was observed by immunofluorescence. Oral prednisolone was commenced under the
      diagnosis of chronic tubulointerstitial nephritis, and she discharged once.
      However, its effects were transient; her renal function deteriorated rapidly and
      hemodialysis was initiated 5 months after her initial check-up. On readmission,
      urinary Bence-Jones protein kappa-type was detected, and examination of bone
      marrow led to a diagnosis of Bence-Jones kappa-type multiple myeloma. Light-chain
      staining using a renal biopsy specimen obtained 2 months earlier showed kappa
      light-chain deposition on tubular basement membranes but not glomeruli. Despite
      undergoing chemotherapy with vincristine, doxirubicin, and dexamethasone, the
      patient died suddenly from a cardiac arrhythmia. Autopsy showed kappa-light-chain
      deposition in the heart, thyroid, liver, lungs, spleen, and ovaries. Congo red
      staining yielded negative results. Typical light-chain deposition disease (LCDD)
      characterized by nodular glomerulosclerosis was observed in the kidneys. This
      case demonstrates that tubulointerstitial nephritis can be an early pathological
      variant of LCDD, which may be followed by accelerated and massive light-chain
      deposition in glomeruli.

PMID- 28509074
TI  - Osteomalacia secondary to renal tubular acidosis due to Sjogren's syndrome: a
      case report and review of the literature.
AB  - A 43-year-old woman was admitted to our hospital because of generalized bone
      pain. Arterial blood gas showed pH 7.266, HCO3- 13.5 mEq/l, and anion gap (AG)
      12. Since her urine pH was 7.0 despite metabolic acidosis with normal AG, we
      diagnosed distal renal tubular acidosis (RTA). Serum phosphate was 2.5 mg/dl, the
      level of beta2 microglobulin was 41100 MUg/l, and aminoaciduria was present.
      These results indicated proximal tubular dysfunction. The radiograph showed
      pseudofracture in the pubic bone, indicating osteomalacia. Bone scintigram showed
      abnormal accumulations of 99mTc-HMDP in multiple joints. Then, her generalized
      bone pain was considered to be a symptom of osteomalacia. Despite the absence of
      overt Sicca syndrome, the evaluation of Sjogren's syndrome (SjS) as a cause of
      distal RTA was performed. Antibodies to the SS-A level was 127U/ml. Tear break-up
      time was 3 s bilaterally and salivary gland scintigraphy showed low uptake of
      99mTc in the submandibular glands and the parotids. Thus, we diagnosed SjS
      finally. Gallium scintigraphy showed mild abnormal uptake in bilateral kidneys,
      suggesting acute tubulointerstitial nephritis. After treatment with prednisolone,
      alfacalcidol, and sodium bicarbonate, bone pain was remarkably relieved.
      Additionally, aminoaciduria disappeared and the level of beta2 microglobulin
      decreased. We speculated that the coincidence of proximal tubular dysfunction and
      distal RTA cause a severe manifestation of osteomalacia.

PMID- 28509075
TI  - List of referees.

PMID- 28509076
TI  - Efficacy of antihistamines on mortality in patients receiving maintenance
      hemodialysis: an observational study using propensity score matching.
AB  - Antihistamines are widely used to treat pruritus in patients receiving
      hemodialysis. In a previous cross-sectional study, we reported an association
      between antihistamine use and the absence of eccentric cardiac hypertrophy in
      patients receiving hemodialysis. Therefore, in this study, we sought to evaluate
      the efficacy of antihistamines on all-cause and cardiovascular mortality in
      patients receiving hemodialysis according to our outpatient dialysis database. We
      used a propensity score matching method. Among the 389 patients receiving
      hemodialysis according to our database, we extracted those taking antihistamines
      and matched them with patients not taking antihistamines using propensity scores
      based on 38 variables. All-cause mortality and cardiovascular mortality were
      estimated by the Kaplan-Meier method, and a log-rank test was used to examine the
      differences between the survival curves. We included 154 patients, or 77 matched
      pairs, from the entire cohort (c-statistic = 0.78, p < 0.0001). There were no
      differences in any background factor between the antihistamine and non
      antihistamine group. During the mean observational period of 5.4 years, 50
      patients died, and the all-cause mortality rate was 27.3% (21 patients) in the
      antihistamine group and 37.3% (29 patients) in the non-antihistamine group (p =
      0.0314). The cardiovascular mortality rate was 16.9% (13 patients) in the
      antihistamine group and 25.9% (20 patients) in the non-antihistamine group (p =
      0.0417). The results of this study suggest that all-cause and cardiovascular
      mortality improved with antihistamine use in patients receiving hemodialysis.
      However, the clinical efficacy of antihistamines needs to be confirmed in a
      prospective randomized study in the future.

PMID- 28509077
TI  - Relationships between cognitive impairment on ADAS-cog and regional cerebral
      blood flow using SPECT in late-onset Alzheimer's disease.
AB  - The aim of this study was to examine brain hypoperfusion and its relationship
      with cognitive dysfunction in late-onset Alzheimer's disease (AD). Forty patients
      with late-onset AD and not receiving acetylcholinesterase inhibitors were
      recruited from outpatient clinics. We examined cognitive function using the
      Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain
      perfusion using single-photon emission computed tomography, and analyzed
      classified gyrus level segments with three-dimensional stereotactic surface
      projection and the stereotactic extraction estimation method level 3. ADAS-cog
      subscales were grouped into three domains: language, memory, and praxis. Patients
      with late-onset AD showed an apparent reduction in regional cerebral blood flow
      (rCBF) with a z score >1.5 in the frontal, temporal, and limbic lobes, with
      lesser reduction in the parietal and occipital lobes. Although hypoperfusion in
      the orbital, rectal, and subcallosal gyri of the frontal lobe was prominent, rCBF
      in the inferior frontal gyrus of the frontal lobe was significantly correlated
      with ADAS-cog total and language and praxis subscale scores. The parahippocampal
      gyrus of the limbic lobe was also significantly correlated with the ADAS-cog
      total, language, and praxis subscale scores. Additionally, the cingulate of the
      limbic lobe was significantly related with ADAS-cog memory. In spite of lesser
      hypoperfusion, the posterior cingulate gyrus of the limbic lobe was significantly
      related with ADAS-cog total, language, and memory subscale scores. Further, each
      subdivision of ADAS-cog was found to be related with various brain regions.

PMID- 28509080
TI  - Evaluation of dose enhancement in presence of gold nanoparticles in eye
      brachytherapy by 103Pd source.
AB  - In recent years, the use of gold nanoparticles in radiation therapy has been
      introduced as a new approach in radiotherapy. The aim of this study is to
      investigate the effect of gold nanoparticles (GNPs) in plaque brachytherapy for
      choroidal melanoma using Monte Carlo (MC) simulation. MCNPX code was used for
      simulation of human eye, 103Pd (model 200) brachytherapy source and the 20 mm
      COMS eye plaque that was loaded with 24 103Pd seeds and standardized by
      Collaborative Ocular Melanoma Study (COMS). The tumour was defined from the inner
      surface of choroid with 0.55 cm height and latticed with gold nanospheres and it
      was filled with different concentrations of 5, 10 and 15 mg/g GNPs, separately.
      Dose rate and dose enhancement factor in tumour and normal tissues of the eye
      (without gold) was examined for this case and compared with gold-water mixture of
      the same concentrations distributed in the tumour. The results show that with
      increasing the concentration of GNPs, the dose in the tumour increases and the
      dose to the normal tissues decreases. Furthermore, the time that is required to
      deliver the prescribed dose to the tumour decreases. In the gold nanosphere case
      for 5, 10 and 15 mg/g concentrations, the DEF in the apex of the tumour are 1.28,
      1.46, 1.44 and at the distance of 6.5 mm in the normal tissue (outside the
      tumour) this factor would be 0.82, 0.73 and 0.68. The comparison between two
      cases of gold nanospheres and gold-water mixture shows that when the gold
      concentrations are defined as mixed with water, the dose enhancement in the first
      depths are higher than when the gold-nanoparticles are distributed inside the
      tumour. Furthermore due to more reduced particle flux for water-mixture case, by
      an increase in the depth the dose enhancement in gold-nanosphere increases
      compared with gold-water mixture case.

PMID- 28509079
TI  - "Pseudo-progression" in advanced thyroid cancer in response to kinase inhibitor
      therapy.

PMID- 28509078
TI  - The effects of vitamin D supplementation on proatherogenic inflammatory markers
      and carotid intima media thickness in subjects with metabolic syndrome: a
      randomized double-blind placebo-controlled clinical trial.
AB  - PURPOSE: Metabolic syndrome may predispose to cardiovascular diseases. Since, in
      recent studies, vitamin D is advocated for cardioprotective roles, this study was
      designed to investigate the effects of vitamin D supplementation on
      proatherogenic inflammatory markers and common carotid intima media thickness in
      subjects with metabolic syndrome. METHODS: This randomized double blind clinical
      trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic
      syndrome were recruited thorough advertisement and randomized to receive either
      vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high
      sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin,
      and common carotid intima media thickness were measured at the beginning and end
      of the study. The study was registered at http://www.irct.ir (code:
      IRCT201409033140N14). RESULTS: Sixteen weeks supplementation with vitamin D
      increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels
      (p < 0.001) in the intervention group. There was also a significant difference in
      parathyroid hormone level at the end of the study (p < 0.001). Vitamin D
      treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline,
      vascular cell adhesion molecule-1 and E-selectin levels decreased significantly
      in vitamin D treated subjects; however, there were no significant differences
      between two groups. No effect of vitamin D supplementation was observed in either
      common carotid intima media thickness or high sensitivity C-reactive protein
      concentrations at the end of the study (p > 0.05). CONCLUSIONS: Vitamin D
      supplementation improved some proatherogenic inflammatory markers in subjects
      with metabolic syndrome. No changes of high sensitivity C-reactive protein and
      carotid intima media thickness were shown after 16 weeks.

PMID- 28509084
TI  - Whole-Exome Sequencing Identifies a Novel Homozygous Frameshift Mutation in the
      MTMR2 Gene as a Causative Mutation in a Patient with Charcot-Marie-Tooth Disease
      Type 4B1.
AB  - Charcot-Marie-Tooth (CMT) disease refers to a heterogeneous group of axonal and
      demyelinating polyneuropathies, characterized by chronic motor and sensory
      dysfunction. CMT is the most common genetic cause of neuropathy. The present
      study aimed to identify the gene mutation responsible for CMT in Ashkenazi Jew
      (AJ) patient. Genomic DNA was extracted from whole blood leukocytes of affected
      family and normal subject. Whole-exome sequencing was performed using the
      Illumina HiSeq2500. The DNA region containing the identified mutation was
      amplified by PCR and sequenced using dye-terminator chemistry and the forward
      primer. Physical examination of the patient revealed weakness and atrophy of the
      lower extremity muscles and Pes cavus foot deformity. Whole-exome sequencing
      indicated that the patient is homozygous for a novel frameshift mutation
      (c.1877_1878insAGAG, p.Arg630fs) in the myotubularin-related protein-2 gene
      (MTMR2), which resulted in an erroneous C-terminal sequence and extension by 15
      amino acids. Patients' parents are healthy, and DNA sequencing analysis indicated
      that both are heterozygotes to the described mutation. The clinical feature of
      the patient may indicate a complete co-segregation of the p.Arg630fs mutation in
      MTMR2 gene with the CMT type 4B1 phenotype. Further studies are needed in order
      to estimate the prevalence of this mutation among AJ.

PMID- 28509081
TI  - Interleukin-6-Mediated Induced Pluripotent Stem Cell (iPSC)-Derived Neural
      Differentiation.
AB  - In an aging society with an increasing threat to higher brain cognitive functions
      due to dementia, it becomes imperative to identify new molecular remedies for
      supporting adult neurogenesis. Interleukin-6 (IL-6) is a promising cytokine that
      can support neurogenesis under conditions of neurodegeneration, and neuron
      replacement is eventually possible due to its agonistic acting soluble receptor
      sIL-6R. Here, we report that activation of the IL-6-signal transducer and
      activator of transcription 3 (STAT3) axis is neurogenic and has potential
      therapeutic applications for the treatment of neurodegenerative diseases such as
      Parkinson's disease (PD).

PMID- 28509082
TI  - Atg7-Mediated Autophagy Is Involved in the Neural Crest Cell Generation in Chick
      Embryo.
AB  - Autophagy plays a very important role in numerous physiological and pathological
      events. However, it still remains unclear whether Atg7-induced autophagy is
      involved in the regulation of neural crest cell production. In this study, we
      found the co-location of Atg7 and Pax7+ neural crest cells in early chick embryo
      development. Upregulation of Atg7 with unilateral transfection of full-length
      Atg7 increased Pax7+ and HNK-1+ cephalic and trunk neural crest cell numbers
      compared to either Control-GFP transfection or opposite neural tubes, suggesting
      that Atg7 over-expression in neural tubes could enhance the production of neural
      crest cells. BMP4 in situ hybridization and p-Smad1/5/8 immunofluorescent
      staining demonstrated that upregulation of Atg7 in neural tubes suppressed the
      BMP4/Smad signaling, which is considered to promote the delamination of neural
      crest cells. Interestingly, upregulation of Atg7 in neural tubes could
      significantly accelerate cell progression into the S phase, implying that Atg7
      modulates cell cycle progression. However, beta-catenin expression was not
      significantly altered. Finally, we demonstrated that upregulation of the Atg7
      gene could activate autophagy as did Atg8. We have also observed that similar
      phenotypes, such as more HNK-1+ neural crest cells in the unilateral Atg8
      transfection side of neural tubes, and the transfection with full-length Atg8-GFP
      certainly promote the numbers of BrdU+ neural crest cells in comparison to the
      GFP control. Taken together, we reveal that Atg7-induced autophagy is involved in
      regulating the production of neural crest cells in early chick embryos through
      the modification of the cell cycle.

PMID- 28509083
TI  - Detection of CSF 14-3-3 Protein in Sporadic Creutzfeldt-Jakob Disease Patients
      Using a New Automated Capillary Western Assay.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal rapidly progressive
      dementia. The detection of 14-3-3 protein in cerebrospinal fluid (CSF) is
      included in the WHO diagnostic criteria for the pre-mortem diagnosis of CJD. The
      aim of this study is to assess CSF 14-3-3 protein analytical and diagnostic
      performances using a new automated capillary Western technology (Simple Western
      technology-SW). For the validation of this assay, samples from a cohort of 268
      patients suspected from sCJD were analyzed: 77 sCJD (including 40 definite sCJD)
      and 191 non-CJD samples were tested using both SW and the current Western Blot
      (WB) assays. Automated capillary Western determination provided better analytical
      performances than WB with a lower intra- and inter-assay variability. Analytical
      interferences such as hemolysis and high total protein concentration known to
      lead to false positive WB results were also assessed using SW assay:
      unfortunately, these interferences still remain confounders of CSF 14-3-3 protein
      determination. Finally, automated capillary Western assay's sensitivity and
      specificity were superior to those of WB assay (93.5 and 95.3%, respectively,
      compared to 92.2 and 84.8% for WB). In conclusion, with a shorter time of
      analysis than WB assays' (4 h versus 1.5 day), automated capillary Western assay
      is an excellent routine alternative method to the currently performed WB assay
      for CSF 14-3-3 protein detection in patients suspected of sporadic Creutzfeldt
      Jakob disease.

PMID- 28509085
TI  - Successful treatment of severe crescentic lupus nephritis by multi-target therapy
      using tacrolimus and mycophenolate mofetil.
AB  - Treatment of severe lupus nephritis (LN) has been controversial, and according to
      recent guidelines and recommendations, cyclophosphamide still remains a first
      line therapy. Herein, we present the case of a 37-year-old female patient who
      developed rapidly progressive glomerulonephritis, which was histologically
      diagnosed as class IV + V LN, with a large number of cellular to fibrocellular
      crescents (62 % of glomeruli). Although the patient was considered to have the
      most severe form of LN, complete remission was achieved within 6 months by multi
      target therapy using tacrolimus and mycophenolate mofetil combined with
      methylprednisolone pulse therapy. Our experience suggests that multi-target
      therapy could be a potential treatment option for patients with severe crescentic
      LN.

PMID- 28509086
TI  - Reoperation after mitral valve repair in viewpoints of kidney injury as well as
      hemolytic anemia.
AB  - A 70-year-old woman developed anemia and kidney injury 10 months after mitral
      valve (MV) repair. Serological findings and Doppler echocardiography suggested
      hemolytic anemia due to mitral regurgitation jet collision with an annuloplasty
      ring (MRCR). Since kidney injury persisted even without exacerbation of anemia
      over 10 months, we performed an MV replacement. The anemia improved rapidly after
      the surgery; however, the renal function remained chronic kidney disease (CKD)
      after reoperation. Kidney injury was thought to be due to iron deposition and
      decreased renal perfusion that caused tubular injury. A comprehensive literature
      review shows that hemolysis due to MRCR in the early postoperative phase (within
      3 postoperative months) can be often ameliorated with endothelialization without
      the need for reoperation; however, hemolysis in the late postoperative phase can
      persist even for a long period without reoperation. Chronic hemolysis can lead to
      kidney injury and progress to CKD even without clinical evidence of exacerbation
      of anemia. Therefore, in cases of late postoperative phase hemolysis, reoperation
      should be considered for better management of kidney injury and hemolytic anemia.

PMID- 28509087
TI  - Postoperative usage of tolvaptan in a patient with aortic valve stenosis
      complicated by Child-Pugh classification B liver cirrhosis and hepatic edema.
AB  - We report the case of an 80-year-old woman with postoperative congestive heart
      failure (CHF) complicated by Child-Pugh classification B liver cirrhosis and
      hepatic edema successfully treated with tolvaptan. The patient suffered from
      liver cirrhosis and underwent partial hepatectomy for a hepatocellular carcinoma
      diagnosed together with a severe aortic valve stenosis. Aortic valve replacement
      was performed under cardiopulmonary bypass. The postoperative course was
      uneventful until CHF and hepatic edema symptoms appeared on postoperative day
      (POD) 2. The symptoms were treated with intravenous human atrial natriuretic
      peptide and oral diuretics. As the condition showed no improvement, oral
      tolvaptan was administered on POD 11 and thereafter, which markedly improved the
      symptoms. This is apparently the first report describing the effectiveness of
      tolvaptan for the postoperative management of fluid balance in a patient with
      cardiac and liver dysfunction.

PMID- 28509088
TI  - Repeated acute kidney injury associated with Mycobacterium gordonae infection.
AB  - Mycobacterium gordonae is a nontuberculous mycobacterium widely distributed in
      the environment. Although M. gordonae is not usually pathogenic and glomerular
      lesions due to M. gordonae are very rare, infection has been reported in both
      immunocompromised patients and healthy persons. We report a case of acute kidney
      injury (AKI) in which M. gordonae was ultimately identified as the cause. A 70
      year-old man was admitted to our hospital because of fever, polyarthritis, and
      AKI. He was a hepatitis B virus carrier, suffered from diabetes, and had a past
      history of erysipelas. No causative bacteria were identified, but coexisting
      infection was suspected. The patient experienced remission with antibiotic
      therapy, but the same symptoms recurred eight times. Blood polymerase chain
      reaction was performed during the 7th recurrence, and M. gordonae was detected.
      Clarithromycin was initiated, but 2 years after initial hospitalization, the
      patient died due to M. gordonae infection. In this case, acute kidney injury was
      a consequence of infection-related glomerulonephritis due to M. gordonae.
      Mycobacterium is difficult to detect by routine culture methods; therefore,
      diagnosis remains challenging.

PMID- 28509089
TI  - Resolution of proteinuria after transarterial embolization of aberrant renal
      artery in a patient with focal segmental glomerulosclerosis.
AB  - A 24-year-old man was admitted to our hospital for persistent proteinuria. He was
      born with a low birth weight but had grown up uneventful until the age of 20 when
      he was found to have proteinuria. Because his body mass index was 30.9 kg/m2 at
      that time, he was diagnosed as obesity-related nephropathy. However, weight
      reduction and administration of ACE inhibitor were minimally effective for the
      amelioration of proteinuria. Ultrasound-guided percutaneous renal biopsy at the
      lower pole of right kidney was performed. As serious bleeding occurred from the
      right aberrant renal artery soon after biopsy, he was treated with transarterial
      embolization (TAE). The day after TAE, proteinuria completely disappeared. Renal
      biopsy showed benign nephrosclerosis with secondary focal segmental
      glomerulosclerosis (FSGS). Proteinuria could be induced by increased blood flow
      and pressure due to abnormal blood supply from aberrant renal artery. This is the
      first report of resolution of proteinuria after TAE of aberrant renal artery in a
      patient with FSGS.

PMID- 28509090
TI  - New-onset systemic lupus erythematosus in a long-term hemodialysis patient with
      acute pleuritis and pneumonitis.
AB  - A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to
      end-stage renal disease of unknown causes, was admitted because of systemic joint
      pain and inflammatory response of unknown etiology that persisted for 1 month.
      Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum
      C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double
      strand DNA. After admission, she progressively developed cough and dyspnea. A
      chest radiograph revealed bilateral ground glass opacity and pleural effusion. A
      thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A
      chest computed tomography showed a pattern of diffuse alveolar damage compatible
      with acute lupus pneumonitis. She fulfilled the American Rheumatism Association
      diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone
      pulse therapy followed by oral prednisone treatment improved the clinical
      symptoms and laboratory abnormalities. ANA was negative 25 years earlier when she
      first started hemodialysis and she had neither clinical nor serological
      abnormalities related to SLE during the last 25 years. Further, she had neither
      received drugs that can cause drug-induced SLE, nor had a history of ultraviolet
      ray exposure, pregnancy, blood transfusion, trauma and smoking. This report
      suggests that new-onset SLE can develop in patients undergoing long-term
      dialysis. Hence, when we encounter dialysis patients with arthralgia and/or
      respiratory disorders, we should consider the possibility of new-onset SLE.

PMID- 28509091
TI  - Clinical remission of IgA nephropathy in an HIV-positive patient after combined
      treatment with tonsillectomy and steroid pulse therapy.
AB  - Various renal diseases other than human immunodeficiency virus (HIV)-associated
      nephropathy, including IgA nephropathy (IgAN), have been recently reported to
      cause chronic kidney disease and end-stage renal disease in HIV-infected
      patients. The case of a 37-year-old HIV-infected male diagnosed as having IgAN
      with proteinuria and microscopic hematuria that was successfully treated with
      tonsillectomy and steroid pulse therapy in combination, resulting in
      disappearance of urinary abnormalities (clinical remission), is reported, the
      first such case in the literature. A renal biopsy revealed mesangial
      proliferation associated with mesangial deposition of IgA and C3, consistent with
      IgAN. Antiretroviral therapy and angiotensin receptor blocker therapy did not
      improve his proteinuria. Therefore, he underwent tonsillectomy and steroid pulse
      therapy, and clinical remission was successfully achieved with no opportunistic
      infections. Clinical remission has continued for more than 3 years even after
      discontinuation of steroid therapy. It appears that combined treatment with
      tonsillectomy and steroid pulse therapy can be a good choice in managing HIV
      infected patients with IgAN as long as secondary infection is strictly and
      continuously monitored.

PMID- 28509092
TI  - A case of primary (AL) amyloidosis with predominantly vascular amyloid deposition
      in the kidney.
AB  - We report a 70-year-old man with primary (AL) amyloidosis with predominantly
      vascular deposition of amyloid diagnosed by renal biopsy, who was successfully
      treated using two chemotherapy regimens. There was rapid elevation of the serum
      creatinine level without remarkable proteinuria or hematuria. Renal histological
      examination showed some thickened arterial walls with amyloid fibril
      accumulation, and only a small amount of amyloid deposition in the glomeruli.
      Immunohistochemical examination was positive for anti-kappa staining. Serum
      immunoelectrophoresis and immunofixation testing did not show monoclonal
      proteins, and urine immunoelectrophoresis did not show Bence-Jones proteins.
      Serum free light chain (FLC) analysis showed that the serum FLC level and FLC
      kappa/lambda ratio were abnormally high for his renal function. He received two
      courses of VAD (vincristine, doxorubicin, and dexamethasone), followed by BD
      (bortezomib and dexamethasone), resulting in a hematologic partial response.
      Renal amyloidosis with vascular-limited amyloid deposition has few urinary
      findings. Early diagnosis of this condition is challenging, because kidney
      biopsies are not usually performed in patients without significant urinary
      findings. We suggest several currently available methods of achieving earlier
      detection of this condition.

PMID- 28509093
TI  - A case of IgG4-related kidney disease complicated by eosinophilic lung disease.
AB  - IgG4-related disease is a systemic chronic inflammatory disorder characterized by
      a high blood level of IgG4 and the organ injuries by marked infiltration of IgG4
      positive plasma cells and fibrosis. A 71-year-old male was hospitalized for a
      cough, malaise and anorexia. IgG4-related disease was suspected due to marked
      elevation of the serum IgG4 level. However, on lung biopsy, only eosinophil
      infiltration was demonstrated with no plasma cell infiltration. Otherwise
      abdominal contrast-enhanced CT showed mild enlargement of the bilateral kidneys
      and many differed contrasted areas and FDG PET-CT. Moreover, renal biopsy
      specimens showed typical tubulointerstitial nephritis with a large number of IgG4
      positive plasma cells infiltration (the IgG4/IgG-positive cell rate, 89 %) and
      fibrosis. We diagnosed this patient as typical IgG4-related kidney disease. He
      was treated by the moderate dose of prednisolone (0.8 mg/kg/day) alone, and
      showed prompt response in the clinical condition, and both the lung and kidney
      lesions. In this case, it was useful for diagnosis of IgG4-related diseases to
      evaluate an image such as abdominal contrast-enhanced CT and FDG PET-CT. Our case
      might be one of the possible patterns of IgG4-related lung diseases. In addition,
      we thought that there might be an association between hypereosinophilia and IgG4
      related kidney disease.

PMID- 28509094
TI  - Calciphylaxis induced by warfarin therapy in a patient with anti-phospholipid
      antibody syndrome associated with systemic lupus erythematosus.
AB  - Calciphylaxis is a life-threatening complication of end-stage kidney disease
      (ESKD) and leads to cutaneous necrosis and gangrene. Various risk factors for
      calciphylaxis have been reported, and warfarin therapy is a particularly strong
      trigger. Here we report the case of 50-year-old woman with ESKD and systemic
      lupus erythematosus who developed calciphylaxis after anti-thrombotic therapy,
      including warfarin, for ischemic skin ulcers due to arteriosclerosis obliterans
      and anti-phospholipid antibody syndrome. Although warfarin improved the
      thrombotic skin ulcers, it might also be a trigger for calciphylaxis.
      Discontinuation of the warfarin and the addition of low-density lipoprotein
      apheresis and sodium thiosulfate infusion failed to improve the gangrene;
      eventually, her legs had to be amputated to prevent lethal infection. The
      histology of the dermal and soft tissue obtained from the amputated legs showed
      typical findings of calciphylaxis. Warfarin is a vitamin K antagonist with
      inhibitory effects on the calcification of regulatory proteins, such as matrix
      Gla protein and fetuin-A. Therefore, the warfarin therapy might have induced
      calciphylaxis in our patient.

PMID- 28509095
TI  - A case of acute renal failure of multiple myeloma due to monoclonal type I
      cryoglobulinemia with thrombotic microangiopathy.
AB  - The term cryoglobulinemia (CG) is used to refer to vasculitis due to so-called
      mixed cryoglobulins containing immune complexes. Although most cases of
      monoclonal CG, called type I CG, are asymptomatic, purpura, skin ulcers, and
      renal failure develop in some cases. Hematological disorders are the underlying
      diseases in most cases, on which the therapeutic strategies available and the
      prognosis of patients depends. We here report a case of a 47-year-old man who had
      pain in both his ankles, with palpable purpura and epistaxis, and presented with
      acute renal failure. Monoclonal immunoglobulin (Ig) G-kappa protein was detected
      and cryoglobulin was also positive. Renal biopsy revealed emboli with a fibrillar
      structure in the glomeruli and renal tubule lumina. The complication of
      thrombotic microangiopathy (TMA) occurred during the course. Therefore, plasma
      exchange and hemodialysis were added to methylprednisolone pulse therapy. The
      treatment was successful, dissipating the purpura. However, the purpura relapsed
      and renal dysfunction progressed when the administration of oral steroids was
      tapered. Bone marrow biopsy was performed again, which indicated an increase in
      abnormal plasma cells. The patient was finally diagnosed as multiple myeloma.
      Then, bortezomib-dexamethasone therapy was initiated. This is the first case of
      type I CG with monoclonal IgG complicated by TMA during the course; it provides
      insight into the pathogenesis of renal dysfunction associated with type I CG.

PMID- 28509096
TI  - Successful treatment by mycophenolate mofetil in a patient with focal segmental
      glomerulosclerosis associated with posterior reversible encephalopathy syndrome.
AB  - It has been reported that cyclosporine A (CsA) treatment may be associated with
      posterior reversible encephalopathy syndrome. We report a 16-year-old man who
      exhibited nephrotic syndrome and posterior reversible encephalopathy syndrome.
      Intensive antihypertensive therapy restored him to consciousness. Renal biopsy
      revealed that he suffered from focal segmental glomerulosclerosis. Although he
      was treated with prednisolone and low-density lipoprotein apheresis therapy, his
      proteinuria remained at high level. Then, mycophenolate mofetil (MMF) with less
      influence on vessel endothelium compared with CsA and tacrolimus was
      administered. Soon after, he reached remission of nephrotic syndrome without
      recurrence of posterior reversible encephalopathy syndrome. This is the first
      case that a young patient of focal segmental glomerulosclerosis with posterior
      reversible encephalopathy syndrome achieved a complete remission by MMF treatment
      without recurrence of posterior reversible encephalopathy syndrome. MMF may be
      effective for young patients of focal segmental glomerulosclerosis especially
      with clinical condition of vascular endothelial damage such as posterior
      reversible encephalopathy syndrome.

PMID- 28509097
TI  - Propylthiouracil-associated rapidly progressive crescentic glomerulonephritis
      with double positive anti-glomerular basement membrane and antineutrophil
      cytoplasmic antibody: the first case report.
AB  - We report a case of propylthiouracil (PTU)-induced double antineutrophil
      cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti
      GBM antibody) disease causing pulmonary-renal syndrome in a 35-year-old Thai
      woman with 10-year history of PTU treatment for thyrotoxicosis. She developed
      clinical symptoms of vasculitis upon receiving long-term PTU treatment.
      Prednisolone treatment and the switching from PTU to methimazole resulted to
      short-term clinical improvement. Nevertheless following termination of steroid
      treatment, she developed recurrent pulmonary hemorrhage and rapidly progressive
      glomerulonephritis. The kidney biopsy showed crescentic glomerulonephritis with
      linear IgG deposit on the glomerular basement membrane although transbronchial
      lung biopsy showed no immune deposit along the alveolar basement membrane. Serum
      testing for p-ANCA was positive and western blot showed positive antibody to the
      alpha-3 chain of collagen type IV. Both ANCA and anti-GBM antibody may play a
      role in the development of end organ damage. To facilitate early and specific
      intervention, clinicians should be aware of the propensity of PTU to cause lupus
      like syndromes with renal involvement. In patients with PTU-induced ANCA
      associated glomerulonephritis, serum anti-GBM antibody test may be useful in the
      early diagnosis of double positive antibodies disease and plasmapheresis should
      be performed without delay.

PMID- 28509098
TI  - HBV reactivation in a patient on chronic haemodialysis treatment.

PMID- 28509099
TI  - A case of acute kidney injury due to secondary retroperitoneal fibrosis caused by
      direct invasion of esophageal squamous cell carcinoma.
AB  - A 71-year-old man who developed renal failure was admitted to our hospital.
      Computed tomography without contrast enhancement showed bilateral hydronephrosis
      together with a soft tissue mass around the abdominal aorta, leading to the
      diagnosis of retroperitoneal fibrosis. Serum levels of immunoglobulin G4 were
      within the normal range. The patient was then evaluated for the presence of
      undiagnosed malignancy as a possible cause of secondary retroperitoneal fibrosis.
      Upper gastrointestinal tract endoscopy demonstrated esophageal cancer. Histology
      of the esophageal lesion and the retroperitoneal mass showed squamous cell
      carcinoma (SCC). Therefore, the retroperitoneal fibrosis was considered to be due
      to the invasion of SCC of the esophagus, and chemotherapy was chosen as the
      treatment. This is the first case report of postrenal failure due to secondary
      retroperitoneal fibrosis caused by the direct invasion of esophageal SCC.
      Physicians should be aware of occult malignancy as the cause of unexplained
      retroperitoneal fibrosis, even clinically silent, to avoid inappropriate
      management or delay in the treatment of potentially life-threatening co
      morbidities.

PMID- 28509100
TI  - Erratum to: Reoperation after mitral valve repair in viewpoints of kidney injury
      as well as hemolytic anemia.

PMID- 28509101
TI  - Effectiveness of plasma exchange for acquired type A hemophilia.
AB  - An 80-year-old man was treated at our hospital for chronic kidney disease,
      diabetes mellitus and hypertension. He presented a bleeding tendency over the
      past several weeks. When he was admitted to our hospital with a consciousness
      disturbance, he had irregular 10-20 cm patches of subcutaneous bleeding.
      Laboratory findings showed prolonged activated partial thromboplastin time (APTT)
      but normal platelet count and prothrombin time. The administration of fresh
      frozen plasma did not control the bleeding tendency and the result of APTT cross
      mixing test suggested the presence of factor VIII inhibitor. The diagnosis of
      acquired hemophilia A was made by a marked decrease in factor VIII activity
      levels (<1 %) and a high titer of factor VIII inhibitor (11 Bethesda units). To
      remove the factor VIII inhibitor and suppress its production, plasma exchange was
      performed and methylprednisolone was administered. Thereafter, the bleeding
      tendency could be controlled with APTT measurement normalization. Plasma exchange
      does not have a first priority in the treatment but our case findings suggested
      that plasma exchange is an effective method for eliminating factor VIII inhibitor
      and alleviating acquired hemophilia A severity.

PMID- 28509102
TI  - Pediatric Sjogren syndrome with distal renal tubular acidosis and autoimmune
      hypothyroidism: an uncommon association.
AB  - A 14-year-old female came with the history of sudden onset weakness; during work
      up, she was found to have hyperchloremic metabolic acidosis with normal anion gap
      and normal renal function suggesting the possibility of renal tubular acidosis
      (RTA). On further evaluation of RTA, she had positive antinuclear antibody, anti
      Ro, and anti-La antibodies. On nuclear scan of salivary glands, her left parotid
      gland was nonfunctional. Her parotid biopsy revealed dilated interlobular ducts
      engulfed by lymphoid cells. She also had autoimmune hypothyroidism as suggested
      by raised TSH and positive anti-TPO antibodies. At admission, her serum potassium
      levels were low and she was treated with intravenous potassium chloride. After
      she recovered from acute hypokalemic paralysis, she was started on oral potassium
      citrate along with phosphate supplements, hydroxychloroquine, oral prednisolone
      and thyroxine supplements. Over the next 6 months, she has significant reduction
      in the dosage of potassium, bicarbonate and phosphate and gained 3 kg of weight
      and 3.5 cm of height. As primary Sjogren syndrome itself is rare in pediatric
      population and its association with renal tubular acidosis is even rarer, we
      suggest considering Sjogren syndrome as a differential diagnosis during the RTA
      work-up is worth trying.

PMID- 28509103
TI  - Combined IgG4kappa and IgG1lambda deposition in the glomerular and tubular
      basement membrane accompanied by autoimmune neutropenia (AIN) and immune
      thrombocytopenia (ITP).
AB  - A 48-year-old male was admitted to our hospital with nephrotic syndrome. Light
      microscopic examination of a renal biopsy specimen showed almost normal
      glomerular appearance, however, immunofluorescence examination revealed linear
      and granular IgG deposits on the glomerular basement membrane (GBM), accompanied
      by slight IgG deposition in the tubular basement membrane (TBM). Further
      investigation of the IgG subclass and light chain staining revealed that the
      glomerular deposits were composed of IgG1 and IgG4, with both kappa and lambda
      light chains, while the tubular deposits were composed of only IgG4 and kappa
      light chains. The electron-microscopic findings of small granular deposits in the
      GBM and TBM closely resembled those of light and heavy chain deposition disease
      (LHCDD). Immunoelectron microscopy confirmed the presence of kappa and lambda
      chains in the GBM and TBM, however, only significant kappa chain deposition was
      found in the TBM. There was no evidence of monoclonal gammopathy. Clinically, the
      patient subsequently developed neutropenia and thrombocytopenia associated with
      the presence of anti-neutrophil antibody and anti-GPIIb/IIIa antibody-producing B
      cells in the blood. Oral steroid administration was initiated, which led to
      amelioration of the neutropenia, thrombocytopenia and proteinuria. This may be a
      very rare case of combined IgG4kappa and IgG1lambda deposition disease
      accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP)
      suggestive of biclonal immunoglobulin deposition disease (BIDD). Investigation of
      the IgG subclass and of the light chains was useful for recognizing the clonality
      of the immunoglobulin deposits in the kidney.

PMID- 28509104
TI  - Autosomal dominant distal renal tubular acidosis caused by a mutation in the
      anion exchanger 1 gene in a Japanese family.
AB  - Autosomal dominant distal renal tubular acidosis (dRTA) is a rare disorder caused
      by a mutation in the AE1 gene encoding the chloride-bicarbonate (Cl-/HCO3-) anion
      exchanger 1 (AE1). Most patients with this disorder present with clinical
      symptoms in adulthood and their phenotype is milder than that of those with
      autosomal recessive dRTA. In this report, we describe a Japanese family with
      autosomal dominant dRTA in which the mother and her daughter presented with
      severe symptoms caused by hypokalemia at 2 years of age. The heterozygous AE1
      mutation G609R, which is a known causative mutation of dRTA, was identified in
      both patients. To our knowledge, this is the first report of a Japanese family
      with autosomal dominant type dRTA caused by an AE1 mutation. We, therefore,
      propose that alterations of AE1 should be considered causative of autosomal
      dominant dRTA even if typical symptoms appear during early childhood and the
      clinical features are severe.

PMID- 28509105
TI  - Acute kidney injury caused by sarcoid granulomatous interstitial nephritis
      without extrarenal manifestations.
AB  - Granulomatous interstitial nephritis (GIN) is one of the renal pathological
      manifestations of sarcoidosis. It is usually clinically silent, but may present
      occasionally as acute kidney injury (AKI). AKI caused by sarcoid GIN without
      extrarenal manifestations is extremely rare. We report a case of a 70-year-old
      man with a history of type 2 diabetes mellitus admitted with progressively
      worsening kidney function. The patient also exhibited anorexia, malaise and
      weight loss. Laboratory tests showed an elevated serum lysozyme level, but the
      serum angiotensin-converting enzyme (ACE) and serum calcium levels were normal.
      Increased uptake was evident only in kidney on gallium 67 scintigraphy. Although
      typical organ involvement of sarcoidosis was not evident, a renal biopsy showed
      granulomatous interstitial nephritis with non-caseating granulomas. No
      medications had been added in the 3 years preceding renal function deterioration.
      Following a bronchoalveolar lavage that revealed a high CD4:CD8 ratio, and a skin
      test that showed negative for tuberculin, a diagnosis of renal sarcoidosis was
      established. On diagnosis, oral prednisolone was initiated and renal function
      improved. The anorexia and malaise also disappeared. This is the extremely rare
      case of AKI caused by sarcoid GIN without extrarenal manifestations or elevated
      serum ACE level.

PMID- 28509106
TI  - Posterior reversible encephalopathy syndrome in a uremic patient with autosomal
      recessive polycystic kidney disease.
AB  - Posterior reversible encephalopathy syndrome (PRES) is characterized by headache,
      seizures, altered mental status, and visual disturbance. It is diagnosed by the
      presence of both clinical symptoms and radiographic findings on the parietal
      occipital lobes. We here report a 61-year-old woman with non-compensative liver
      cirrhosis and chronic kidney disease, presenting with uremia-induced PRES. She
      expressed loss of consciousness and subsequent visual disturbance, during the
      progression of uremia. She was treated with hemodiafiltration therapy, and the
      symptoms of PRES fully improved. The case is of particular interest, in that the
      appearance of abnormal findings on magnetic resonance imaging was delayed more
      than 2 weeks, as compared to that of clinical symptoms. The etiology of chronic
      kidney disease in the patient was considered to be autosomal recessive polycystic
      kidney disease, and we performed DNA sequencing analysis on the polycystic kidney
      and hepatic disease 1 gene. Two homozygous missense mutations were found in the
      patient and may combinatorially affect the disease. This case raises a
      possibility that the incidence of PRES is much higher if the radiological
      examination is performed more frequently.

PMID- 28509107
TI  - Concurrent acute spontaneous tumor lysis syndrome complicated with multiple organ
      failure in a patient with pre-existing undiagnosed lung cancer.
AB  - Acute kidney injury, a common complication associated with malignancy, occurs in
      various clinical situations for numerous reasons. Acute tumor lysis syndrome
      (TLS) is possibly the most significant cause of acute kidney injury in cancer
      patients, because it is fulminant at onset and associated with severe metabolic
      derangements. Acute spontaneous tumor lysis syndrome is rare and most of the
      related malignancies belong to hematologic malignancies but it has seldom been
      investigated as bulky or advanced metastatic non-hematologic malignancies. TLS
      comprises a clinical laboratory derangement of cellular metabolism which can lead
      to acute renal impairments, cardiac arrhythmia, seizures and patient demise.
      Prevention and treatment of tumor lysis syndrome depends on early recognition of
      at-risk patients, volume repletion and xanthin oxidase inhibitors. In addition,
      in patients with high risk tumor types, prophylactic use of rasburicase before
      chemotherapy is required. If dialysis is required, continuous modalities may be
      favored, particularly in patients with more severe TLS. This case report
      discusses a 79-year-old man with controlled Alzheimer's disease presented with
      picture of septic shock and multiorgan dysfunction (acute kidney injury, acute
      lung injury, acute brain injury) pulmonary suppuration in the right lung field
      due to aspiration pneumonia with infection-induced systemic inflammatory response
      (SIRS) was diagnosed. Further work-up revealed lung cancer on chest CT scan.
      Antibiotic, respirator and hemodialysis treatment improved his condition but died
      several days later. Acute spontaneous TLS may present in association with
      infectious SIRS and multiple organ failure, the combination of which results in
      significant mortality.

PMID- 28509108
TI  - Simultaneous nephrotic syndrome and hepatitis in secondary syphilis: case report
      and review of the literature.
AB  - A 66-year-old man presented with a penile ulcer, an acute clinical onset of
      nephrotic syndrome and hepatitis. Secondary syphilis was diagnosed on the basis
      of the history of rash and the result of strongly positive serological test for
      syphilis. A renal biopsy demonstrated membranous glomerulonephritis with
      subepithelial electron-dense deposits. After treatment with amoxicillin for 2
      weeks, he achieved clinical recovery. It is important to recognize syphilis as a
      reversible cause of nephrotic syndrome and acute hepatitis because antibiotic
      therapy can result in complete remission.

PMID- 28509109
TI  - A case of acute EPS with local cocoon formation in a patient on peritoneal
      dialysis.
AB  - Encapsulating peritoneal sclerosis is a rare and life-threatening complication of
      long-term peritoneal dialysis and until now there is no established medical
      treatment. Many factors have been incriminated in its pathogenesis but they do
      not explain all risk conditions. We report our experience and we investigate the
      predisposing factors. Probably unidentified factors make some patients more
      susceptible to developing encapsulating peritoneal sclerosis.

PMID- 28509110
TI  - Prominent hyperplasia of renin-producing juxtaglomerular apparatus after chronic
      and complete blockade of the renin-angiotensin system in adult IgA nephropathy.
AB  - Juxtaglomerular apparatus (JGA) hyperplasia rarely happened in renal biopsy and
      has been controversial clinically, because synthesis and secretion of renin were
      susceptible to the effect of clinical condition and medication. Here we present
      the case of a 39-year-old who got JGA hyperplasia of IgA nephropathy (IgAN) after
      long-term inhibition of the renin-angiotensin system (RAS) with an angiotensin
      receptor blocker (ARB), and a direct renin inhibitor (DRI) in combination with a
      diuretic. He was diagnosed with IgAN in his first renal biopsy, and was treated
      with supra-maximal dosages of ARB, DRI and a diuretic. In the second biopsy,
      because of the massive proteinuria and occurrence of steroid-induced diabetes, it
      was revealed that the area and the number of JGA cells were strikingly increased
      in observed glomeruli. Immunohistopathologically, the both specimens were stained
      by human renin antibody. The hyperplastic JG cells contained a large amount of
      renin granules. Putative renin granules were observed in some interstitial cells
      adjacent to an afferent arteriole by electron microscopy. The increasing response
      of renin granules co-localized in prominent JGA hyperplasia should be worried
      while physicians treat hypertensive patients with potent RAS inhibitors and
      diuretics even though they have diabetes. This is the first report showing a
      clinical course of forming prominent JGA hyperplasia directly after a full
      combination of RAS inhibitors and diuretics in adult IgA nephropathy.

PMID- 28509112
TI  - Response to the Letter to the Editor by Arndt van Ophoven.

PMID- 28509113
TI  - Re: Management of device-related complications after sacral neuromodulation for
      lower urinary tract disorders in women: a single center experience : Tilemachos
      Kavvadias, Markus Huebner, Sara Yvonne Brucker, Christl Reisenauer.

PMID- 28509111
TI  - Synchrony effect on joint attention.
AB  - Research on joint attention has demonstrated that individuals are sensitive to a
      coactor's attentional relation to jointly attended stimuli. Within a
      chronobiological approach, a study was conducted to assess whether the presence
      of joint attention, as measured by the joint Navon effect, was influenced by the
      synchrony effect. Pairs of participants sitting next to each other were required
      to respond to the identity letters in a go/no-go Navon task. The joint Navon task
      was performed by morning, intermediate and evening types (81 pairs) at different
      times of day (09:00-10:00; 13:00-14:00; 17:00-18:00). The joint Navon effect on
      task performance was highlighted at the optimal time of day (in the morning for
      morning types, in the early afternoon for intermediate types and in the evening
      for evening types), but it disappeared or decreased at the non-optimal time of
      day, with the exception of evening types. The results demonstrated that joint
      attention was affected by the synchrony effect.

PMID- 28509115
TI  - Erratum to: Valorization of Proteins from Co- and By-Products from the Fish and
      Meat Industry.

PMID- 28509114
TI  - Implicating the potential role of orexin in hypertension.
AB  - Orexins (orexin A and orexin B), neuropeptides of hypothalamic origin also known
      as hypocretins, have been well documented for regulating the different
      physiological functions including feeding, sleep wakefulness, stress, and reward.
      However, from the past few years, orexins have evolved as an emerging biomarker
      for various endocrine disorders including diabetes mellitus and obesity which
      ultimately leads to various cardiovascular risk factors. Orexins exist in two
      isoforms orexin A and orexin B and exert their effect by acting on the G protein
      coupled receptors orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R).
      Furthermore, localization of orexinergic neurons in the different brain regions
      has been involved in regulating the cardiovascular and sympathetic activity.
      Growing evidences have addressed the potential role of orexins including orexin A
      and orexin B in modulating the hypertension via exerting their effect on the mean
      arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity
      (RSNA). The present review summarizes the central role orexins in the
      hypertension along with the possible mechanism.

PMID- 28509118
TI  - Anti-glomerular basement membrane disease accompanied by systemic lupus
      erythematosus presenting central nervous system involvement.
AB  - We report a case of rapidly progressive glomerulonephritis caused by anti
      glomerular basement membrane (GBM) disease accompanied by systemic lupus
      erythematosus (SLE) presenting central nervous system involvement in a 32-year
      old Japanese male. He was admitted to our hospital because of a 3-week history of
      fever and rapidly failing renal function requiring hemodialysis (HD). Laboratory
      tests showed anti-GBM antibody elevation with a value of 16,385 units/ml. On day
      85, he had generalized tonic-clonic seizure. Brain magnetic resonance T2 Flair
      imaging showed multiple high intensity lesions in a broad area. We made a
      diagnosis of central nervous system involvement in SLE based on positivity for
      antinuclear and anti-DNA antibodies, hypocomplementemia, and discoid skin rash.
      After combined therapy consisting of plasma exchange, HD, and steroid pulse, the
      patient made a good recovery without any residual neurological sequelae, though
      kidney dysfunction requiring maintenance HD remained. Anti-GBM antibody finally
      became undetectable on the 144th hospital day.

PMID- 28509116
TI  - Tonic regulation of stationary asynchronous firing of a neural network.
AB  - The impact of tonic conductance upon population activity was investigated. An
      extra tonic transmembrane current through GABA-activated extrasynaptic GABA A 
      receptors was found to control stationary asynchronous firing both quantitatively
      and qualitatively. Quantitative regulation consisted in alterating a current
      level of stationary population activity while qualitative regulation manifested
      itself in appearance of resilient asynchronous spiking in case GABA reversal
      potential exceeded a certain threshold. The study was based on a modified rate
      model after Wilson and Cowan and backed up with a computer simulation of an
      explicit network model.

PMID- 28509117
TI  - The theory of multiple stupidities: education, technology and organisation in
      Arabia.
AB  - Traditional perspectives have envisaged intelligence as one entity dominated by a
      single set of abilities (i.e. cognitive abilities), whereas modern perspectives
      have defined intelligence in various shapes (e.g. linguistic, musical and
      interpersonal intelligences). By the same token, traditional perspectives have
      examined stupidity as one set of inabilities (i.e. cognitive inabilities).
      However, it is not clear whether modern perspectives have discussed whether
      stupidity exists in various forms-in the same way as they have envisaged
      intelligence. To address this limitation, 257 university members were asked to
      share what they perceived as being stupid educational and technological practices
      in their institutions. Analysis of the data suggested three concepts were
      important to the members: moral, spatial and administrative stupidities. That is,
      stupidity is perceived to come in the form of failing to meet certain moral,
      spatial and administrative values. This implies that modern perspectives may
      conceptualise stupidity differently from traditional perspectives, seeing it as
      going beyond cognitive inabilities and viewing it as existing in various forms
      (e.g. moral, spatial and administrative stupidities). Thus, there are multiple
      stupidities as there are multiple forms of intelligence. A strength of this
      research is that it views stupidity through an organisational and qualitative
      lens, although some may traditionally expect such a topic to be examined
      quantitatively through psychometric and biological approaches.

PMID- 28509119
TI  - Serial sonographic findings during progression from acute pyelonephritis to renal
      abscess: a rare case report.
AB  - Renal abscess, accumulation of infective fluid in the kidney, is a rare
      pathology. Currently, no reports of the serial imaging changes of acute
      pyelonephritis (APN) progressing to renal abscess exist. We report clinical and
      serial sonographic findings of a patient with hyper-immunoglobulin E syndrome, a
      primary immunodeficiency, who developed APN that progressed to renal abscess.
      Renal ultrasonography revealed that echogenicity of infectious lesions
      dramatically changed from isoechoic to hyperechoic and to hypoechoic during
      progression. These findings are useful for differential diagnosis of APN, acute
      focal bacterial nephritis, and renal abscess.

PMID- 28509120
TI  - Complex glomerular pathology of thrombotic microangiopathy and focal segmental
      glomerulosclerosis forms tumor-like mass in a renal transplant donor with severe
      renovascular hypertension.
AB  - The pathogenesis of glomerular hypertension-mediated FSGS and its histological
      variations in humans remains unknown. A 47-year-old man developed nephrotic
      syndrome, renal dysfunction, and malignant hypertension 2 years after donating a
      kidney to his son. The donor's remnant kidney developed renal mass at an upper
      pole which was fed by an aberrant artery that branched from the root of the renal
      artery. Furthermore, the main non-aberrant renal artery demonstrated severe
      stenosis that caused renovascular hypertension, resulting in malignant
      hypertension. Upon radiological examinations, a tumorous mass was detected.
      Because of progressive renal dysfunction, nephrectomy was performed. The kidney
      revealed a diffuse distribution of complex FSGS lesions, i.e., a random
      combination of cellular/collapsing FSGS and glomerular thrombotic
      microangiopathy, confined to the renal mass, whereas such lesions were absent in
      the non-mass portion. This indicated that severe glomerular hypertension alone
      caused FSGS with TMA features. Heterogeneous FSGS lesions let us surmise that
      glomerular hypertension promoted simultaneous damages in endothelial cells and
      podocytes, which synergistically progressed to glomerulosclerosis. This unique
      case uncovers causal relationships between unusual glomerular hypertension and
      severe forms of FSGS that was possibly caused by the disruption of homeostasis
      sustained by podocytes and endothelial cells.

PMID- 28509121
TI  - Antithyroid drug-associated MPO-ANCA-positive tubulointerstitial nephritis in a
      type 2 diabetes patient: a case report.
AB  - A 54-year-old man diagnosed with type 2 diabetes and hyperthyroidism was
      prescribed propylthiouracil (PTU) after the patient developed hepatic dysfunction
      on thiamazole. At 50 mg/day of PTU, he was stable with thyroid-stimulating
      hormone receptor and thyrotropic antibody titers remaining stable. After four
      years of taking PTU, he was referred to the Department of Nephrology due to a
      rapid increase in his serum creatinine (Cr) level. He showed impaired renal
      function (Cr 2.26 mg/dL; estimated glomerular filtration rate (eGFR), 25 mL/min).
      In addition, urinary beta2-microglobulin (beta2 MG) was increased to 71,980 MUg/L
      and was positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody
      (ANCA) (33.9 U/mL). Gallium scintigraphy demonstrated a remarkable accumulation
      in both kidneys. The patient was diagnosed with tubulointerstitial nephritis
      based on a renal biopsy, the results of which suggested that it might have been
      induced by PTU. He was treated with prednisolone (PSL) at 30 mg/day. As a result,
      within two weeks, Cr, eGFR, and urinary beta2 MG levels were progressively
      improved to 1.72 mg/dL, 34 mL/min, and 22,020 MUg/L, respectively. Therefore, we
      tapered off the PSL with a dose of 5 mg/day after approximately one year. There
      have been no exacerbated renal function parameters. Although there are many
      reports on patients developing MPO-ANCA-positive crescentic glomerulonephritis
      after the administration of PTU, we report on a relatively rare case in which
      interstitial nephritis occurred after the administration of PTU.

PMID- 28509122
TI  - Severe hyponatremia in a patient with schizophrenia associated with prolonged
      consciousness disturbance.
AB  - Hyponatremia presents with various central nervous system symptoms during its
      course and treatment. We treated a patient who presented with a prolonged
      consciousness disorder and was suspected of having complications of neuroleptic
      malignant syndrome and osmotic demyelination syndrome (ODS) during the treatment
      for his hyponatremia, which was caused by syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH). The patient was a 30-year-old Japanese man who had
      been under treatment for schizophrenia. He presented with profound hyponatremia
      (96 mEq/L) and a consciousness disorder. Because he was taking a number of
      antipsychotic drugs and since psychogenic polydipsia was present along with
      laboratory findings, the patient was diagnosed with SIADH. However, the
      consciousness disorder reappeared after his serum sodium concentrations were
      normalized, and it persisted over a long period. Although ODS was suspected from
      the clinical course and imaging findings, there were several inconsistencies,
      such as the lack of quadriplegia. The patient also showed muscular rigidity and
      fever, and we, therefore, diagnosed complications of malignant hyperthermia
      syndrome caused by the discontinuation of all antipsychotic drugs at the time of
      onset. There have been no reports of complications of these two conditions, and
      we report this case for its clinically valuable information.

PMID- 28509123
TI  - Serum calcitriol levels in a patient with X-linked hypophosphatemia complicated
      by autosomal dominant polycystic kidney disease.
AB  - Serum calcitriol [1,25(OH)2D] levels are low normal in the presence of
      hypophosphatemia in X-linked dominant hypophosphatemic rickets (XLH) due to
      elevated serum fibroblast growth factor 23 (FGF23) levels. We report a peculiar
      finding of markedly elevated serum 1,25(OH)2D levels in a patient with XLH
      complicated by autosomal dominant polycystic kidney disease (ADPKD) and retinitis
      pigmentosa (RP). She was diagnosed with XLH, ADPKD and RP at the age of 5, 13 and
      15 years, respectively. After the diagnosis of ADPKD, the 1,25(OH)2D levels
      increased up to 282 pg/mL treated with a pharmacological dose of 1alphaOHD3
      (1alphaOHD3). At the age of 17 years, under a physiological dose, serum 25
      hydroxyvitamin D3 (25OHD3) and 1,25(OH)2D levels were 14.0 ng/mL and 93 pg/mL,
      respectively. With off-therapy for 3 days, the latter decreased to 9 pg/mL with
      an increased ratio of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)/25OHD3. Serum
      FGF23 and circulating soluble alpha-klotho (sKlotho) levels were 552 and 873
      pg/mL, respectively, with the latter being almost half of the normal control.
      Since the coexistence of elevated serum FGF23 and 1,25(OH)2D levels contradicted
      the conventional FGF23 actions, we speculated on the possible association of
      decreased sKlotho with the peculiar vitamin D metabolism, although mechanisms in
      detail remained unknown.

PMID- 28509124
TI  - Metastatic renal cell carcinoma with undetectable renal mass presenting as
      lymphadenopathy.
AB  - Renal cell carcinoma has the ability to metastasize to any organ; about 16 % of
      affected patients present initially with metastasis. However, it is rare for this
      tumor to present with metastasis from an unidentified primary. The current use of
      immunohistochemistry and molecular genetics has enabled clinicians to reach a
      precise diagnosis. It has been hypothesized that the treatment protocol for
      metastatic renal cell carcinoma can be applied to cases with undetectable
      primary. In this paper, a novel case of metastatic renal cell carcinoma
      presenting with lymphadenopathy with no evidence of a primary renal lesion is
      reported from Kuwait cancer center.

PMID- 28509125
TI  - A case of PR3-ANCA-positive anti-GBM disease associated with intrarenal arteritis
      and thrombotic microangiopathy.
AB  - Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti
      neutrophil cytoplasmic antibody (ANCA) is occasionally reported and termed
      "double positive" disease. Interestingly, the majority of "double positive" ANCA
      is myeloperoxidase (MPO)-ANCA, and some of the MPO-ANCA-positive cases reveal
      intrarenal arteritis indicating an ANCA-associated renal lesion. In contrast,
      proteinase 3 (PR3)-ANCA-positive "double positive" disease had rarely been
      reported, and as far as we know, none of the cases showed intrarenal arteritis.
      Herein, we report a case of PR3-ANCA-positive "double positive" anti-GBM disease
      presenting with pulmonary-renal syndrome and hemolytic uremic syndrome. The
      kidney biopsy showed crescentic glomerulonephritis, intrarenal arteritis, and
      thrombotic microangiopathy. This case newly describes PR3-ANCA-associated
      intrarenal arteritis in "double positive" anti-GBM disease.

PMID- 28509126
TI  - Gram-negative sepsis following biopsy of a transplant recipient with asymptomatic
      allograft pyelonephritis.
AB  - Pyelonephritis post-renal transplantation is common and in up to 50% of cases can
      be asymptomatic. Transplant pyelonephritis shares a lot of histopathological
      features with acute cellular rejection. We present a case of asymptomatic acute
      graft pyelonephritis where a renal biopsy was complicated by sepsis, and discuss
      the difficulties in interpretation of renal histology in the setting of
      transplant pyelonephritis where rejection may also be a possibility, but
      differentiation is challenging.

PMID- 28509127
TI  - Membranous glomerulonephropathy in a patient with bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is a common autoimmune blistering disease that can be
      complicated by autoimmune disorders. We describe a patient with BP who developed
      membranous glomerulonephropathy (MN). Proteinuria decreased during the clinical
      course as anti-BP180 antibody titers decreased. This finding suggested an
      association between the pathogenesis of these two diseases in terms of
      immunological disorders.

PMID- 28509128
TI  - A case of rapid amelioration of hepatitis C virus-associated cryoglobulinemic
      membranoproliferative glomerulonephritis treated by interferon-free directly
      acting antivirals for HCV in the absence of immunosuppressant.
AB  - Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by
      the immune complex deposition in small- and medium-sized arteries and most often
      due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests
      as refractory glomerulonephritis or nephritic syndrome. Patients with mixed
      cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis
      should receive immunosuppressive therapy. After disease stabilization, patients
      should receive concurrent therapy for the underlying HCV infection. The standard
      therapy of a chronic HCV infection is IFN monotherapy or IFN combined with
      ribavirin; however, after the introduction of direct-acting antivirals (DAAs),
      the standard therapy for patients with HCV genotype 1 has dramatically changed.
      We report a case of HCV-associated cryoglobulinemic membranoproliferative
      glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir,
      which are IFN-free DAAs for HCV, in combination with angiotensin II receptor
      blocker without immunosuppressive therapy. The patient developed severe nephrotic
      syndrome with progressive kidney dysfunction. Blood examination revealed a high
      copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia
      of IgM-kappa, and hypocomplementemia. Histological analysis showed MPGN type 1.
      These findings were compatible with those observed in HCV-associated
      cryoglobulinemic MPGN. This case offers original evidence for the application of
      newer generation of IFN-free DAAs in the treatment of HCV-associated
      cryoglobulinemic nephropathy.

PMID- 28509129
TI  - Successful long-term effects of direct renin inhibitor aliskiren in a patient
      with atherosclerotic renovascular hypertension.
AB  - A 64-year-old man visited our hospital with complaints of misty vision and
      ophthalmalgia. On admission, his blood pressure (BP) was high at 220/135 mmHg
      with no past history of hypertension, and he had choked discs. He was tentatively
      diagnosed as having idiopathic intracranial hypertension, and was later found to
      have atherosclerotic unilateral renovascular hypertension (RVH) based upon the
      extremely high plasma renin activity together with the radiological image tests.
      On day 3, combined antihypertensive therapies consisting of oral angiotensin II
      receptor blocker (ARB) and Ca channel blocker (CCB) along with intravenous CCB
      induced an abrupt BP lowering which led to deterioration of his renal function,
      progressing into acute kidney injury (AKI). Cessation of the ARB and reduction of
      the CCB dose ameliorated the AKI-related decline in renal function. On day 17, as
      he was reluctant to receive surgical intervention, he was treated with a direct
      renin inhibitor, aliskiren, combined with a half-dose CCB as a maintenance
      antihypertensive therapy. The therapy has proven not only successful to
      chronically maintain his renal function but was also capable of controlling his
      BP in the neighborhood of 130/85 mmHg over a period of 2 years. The present case
      suggests that the direct renin inhibition with aliskiren can be a safe and useful
      antihypertensive option to control hypertension and to preserve renal function in
      patients with atherosclerotic unilateral RVH.

PMID- 28509130
TI  - Acute pulmonary thromboembolism occurring during treatment with tolvaptan in a
      patient with autosomal-dominant polycystic kidney disease.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent cystic
      kidney disease, with approximately half of the patients reaching end-stage renal
      disease by the age of 60. Tolvaptan prevents renal cyst growth by inhibiting
      intracellular cyclic AMP and is recommended for patients with ADPKD. Reports of
      thrombotic complications with tolvaptan have been limited. We report a case of a
      60-year-old man who developed thromboembolisms during tolvaptan treatment for
      ADPKD. The patient started tolvaptan in July 2014. He was brought to our hospital
      in February 2015 with a sudden onset of dyspnea and chest pain after 6 days of
      persistent watery diarrhea. Blood tests revealed enhanced coagulation and
      fibrinolysis, and contrast-enhanced computed tomography confirmed the presence of
      multiple thromboembolisms. Venous thromboembolism (VTE) with acute pulmonary and
      lower extremity thrombi was diagnosed, and the patient was immediately admitted.
      Tolvaptan was discontinued on admission, and intravenous fluid loading and
      monteplase were started. Subsequently, chest pain and dyspnea resolved, with
      thrombi resolution occurring by day 14; the patient was discharged on day 18 in
      stable condition. VTE was attributed to continued tolvaptan during diarrhea and
      dehydration; tolvaptan itself was not associated with enhanced coagulability.
      Dehydrated patients with ADPKD, such as the patient in this case, are at an
      increased risk for thrombus formation. Proper education should be provided to
      maintain appropriate fluid status and discontinue tolvaptan upon volume
      depletion.

PMID- 28509131
TI  - Growth hormone therapy for a patient with idiopathic Fanconi syndrome and growth
      hormone deficiency.
AB  - Idiopathic Fanconi syndrome (FS) is characterized by a generalized dysfunction of
      the renal proximal tubules. Patients with FS often exhibit growth retardation due
      to complex factors, such as hypophosphatemia, metabolic acidosis, disturbed
      vitamin D metabolism and hypokalemia. To date, one FS patient has been reported
      to exhibit growth failure due to growth hormone deficiency (GHD), but the long
      term clinical course of recombinant human GH (rhGH) therapy has not been
      reported. At 10 months of age, the patient was admitted to our hospital due to
      growth failure. Blood and urinary biochemical abnormalities, such as
      hypophosphatemia, metabolic acidosis, glycosuria and low-molecular-weight
      proteinuria, indicated a generalized dysfunction of the renal proximal tubules.
      The presence of cystinosis, collagen diseases, toxic agents and metabolic
      diseases were excluded. These features are compatible with idiopathic FS.
      Treatment with high-dose alkali, potassium citrate, phosphate buffer,
      hydrochlorothiazide and vitamin D supplement was initiated. The biochemical
      abnormalities achieved nearly normal values, and the patient's height was within 
      2.5 SD at the age of 2 years. However, his height did not continue to increase at
      the same rate and gradually declined to -2.9 SD at 4 years of age. GH stimulation
      test demonstrated GHD. After initiation of rhGH therapy, his height improved to 
      2.0 SD at the age of 9 years with no adverse effects. In conclusion, we report
      the case of a patient with FS and GHD who continued rhGH therapy for 5 years. The
      differential diagnosis of GHD should also be considered for FS patients with
      short stature.

PMID- 28509132
TI  - Transient Fanconi syndrome in two preterm infants with hydronephrosis and urinary
      tract infection.
AB  - Type IV renal tubular acidosis is known to occur in obstructive uropathy with
      urinary tract infection. Fanconi syndrome, however, has not been described in
      these settings. We report two preterm infants who developed Fanconi syndrome
      associated with hydronephrosis and urinary tract infection. Patient 1 is a boy
      with 21 trisomy, bilateral renal hypoplasia and bilateral vesicoureteral reflux
      delivered at 35 weeks' gestation. At postnatal day 42, he developed Fanconi
      syndrome after urinary tract infection, which persisted until the surgical
      correction of vesicoureteral reflux. Patient 2 was delivered at 35 weeks'
      gestation. At postnatal day 9, he was admitted for severe dehydration. He had
      phimosis and ultrasonography showed left pelviectasis. Laboratory data were
      compatible with Fanconi syndrome, which resolved spontaneously after fluid
      therapy. Subsequently urine culture grew bacteria and treatment for infection and
      topical corticosteroid for phimosis were performed. DMSA scintigraphy performed
      later showed left renal scar. Tubular cell stretch, due to vesicoureteral reflux
      in Patient 1 and phimosis in Patient 2, and urinary tract infection in
      association with immaturity of tubules are thought to have caused Fanconi
      syndrome.

PMID- 28509133
TI  - Denosumab for treatment of immobilization-related hypercalcemia in a patient with
      end-stage renal disease.
AB  - The efficacy and safety of denosumab for the treatment of immobilization-related
      hypercalcemia in end-stage renal disease remain uncertain. We describe the case
      of a hemodialysis patient with immobilization-related hypercalcemia who was
      successfully treated with denosumab. A 79-year-old man admitted for hemodialysis
      after sustaining an acute kidney injury developed immobilization-related
      hypercalcemia due to the impairment resulting from an acute myocardial
      infarction, acute heart failure, and catheter-related bloodstream infection.
      After admission, the patient's corrected serum calcium rose to 12.9 from 8.8
      mg/dL. A bisphosphonate (alendronate) was administered, but it was ineffective.
      Subsequently, treatment with denosumab proved to be effective and his corrected
      serum calcium level declined to 9.3 mg/dL within 1 week. Hypocalcemia, which is
      an adverse effect of denosumab, was prevented using active vitamin D and calcium
      supplementation, and his calcium level stabilized. Thus, our case demonstrates
      that denosumab is a viable therapeutic option for dialysis patients experiencing
      immobilization-related hypercalcemia.

PMID- 28509134
TI  - Two cases of atypical hemolytic uremic syndrome (aHUS) and eosinophilic
      granulomatosis with polyangiitis (EGPA): a possible relationship.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by
      hemolysis, thrombocytopenia, and renal failure. It is related to genetic
      mutations of the alternative complement pathway and is difficult to differentiate
      from other prothrombotic microangiopathies. Eosinophilic granulomatosis with
      polyangiitis (EGPA) (Churg-Strauss syndrome, CSS) is a systemic ANCA-associated
      vasculitis and a hypereosinophilic disorder where eosinophils seem to induce cell
      apoptosis and necrosis and therefore, vasculitis. Here, we report the case of two
      CSS patients with a genetic complement disorder consistent with aHUS diagnosis.
      Both patients showed histologic features that supported the diagnosis of CSS, and
      a genetic complement study confirmed the suspected aHUS diagnosis. In the case
      where eculizumab was administered, the global response was excellent. There is
      very limited understanding of the genetics and epidemiology of both, atypical HUS
      and EGPA, but considering our two patients we suggest that an etiopathogenic link
      exists among patients diagnosed with both entities.

PMID- 28509135
TI  - Renal-limited vasculitis with elevated levels of multiple antibodies.
AB  - Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis that presents with crescentic glomerulonephritis
      with no other organ involvement. Although several studies reported patients with
      crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA
      and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane
      (GBM) antibody, patients positive for all three antibodies, i.e., triple-positive
      patients, were rarely reported. We herein report the case of a male with pauci
      immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and
      anti-GBM antibody. Renal biopsy led to the definitive diagnosis of RLV with pauci
      immune-type crescentic glomerulonephritis. Fluorescence immunostaining showed no
      linear deposition of IgG on GBM, indicating no involvement of anti-GBM associated
      diseases. Intensive therapy, including prednisolone, plasma exchange, and
      intravenous cyclophosphamide, was effective. We report the case of triple
      positive patient with crescentic glomerulonephritis, who was successfully treated
      with glucocorticoid, plasma exchange, and cyclophosphamide, suggesting that
      treatment for RLV in the patient with serological triple antibodies positivity in
      the absence of linear IgG deposition could benefit from the combination therapy
      regimen for plasma exchange and primary induction of remission against
      microscopic polyangiitis.

PMID- 28509136
TI  - Primary hepatic leiomyosarcoma in a patient with autosomal dominant polycystic
      kidney disease.
AB  - Primary hepatic leiomyosarcoma is an extremely rare tumor. The diagnosis is
      difficult, and its etiologic factors have not been clarified. A 63-year-old woman
      with numerous cysts in her kidneys and liver was diagnosed with autosomal
      dominant polycystic kidney disease (ADPKD). Several members of her family also
      had ADPKD. She underwent treatment with tolvaptan to inhibit cyst growth and slow
      the decline in kidney function. Eight months after the start of the therapy, she
      was hospitalized with fatigue and fever of unknown origin. Diagnostic imaging
      showed a very large hepatic tumor, and histologic examination of a fine-needle
      biopsy specimen revealed the tumor to be malignant. Differentiation between
      carcinoma and sarcoma was difficult based on the histological findings. The tumor
      was thought to be excisable; therefore, hepatic resection was attempted. At the
      time of surgery, as the tumor had grown larger than when imaged, complete
      resection was impossible. However, a part of the tumor was resected.
      Histopathological and immunohistological examinations of the surgical specimen
      confirmed a primary hepatic leiomyosarcoma. Whether the tumor was associated with
      the presence of ADPKD remains unclear, however, this is the first report of the
      combination of these two diseases in a patient.

PMID- 28509137
TI  - Successful treatment by tocilizumab without steroid in a very severe case of
      TAFRO syndrome.
AB  - Successful use of tocilizumab (TCZ) to treat TAFRO syndrome has recently been
      reported. In those cases, TCZ was used with steroid. We present herein the case
      of a 59-year-old man with very severe TAFRO syndrome who was successfully treated
      using TCZ without steroid. He showed rapidly progressive anasarca, acute renal
      failure and very severe thrombocytopenia. We initially used steroid, but its
      efficacy was limited. Moreover, steroid use had to be stopped as soon as
      possible, because hemorrhagic shock developed due to severe duodenal ulcer. After
      overcoming infections (about 40 days after stopping steroid), administration of
      TCZ was started and the patient was discharged in clinical remission.

PMID- 28509138
TI  - Juvenile nephronophthisis and dysthyroidism: a rare association.
AB  - Nephronophthisis, an autosomal recessive kidney disease, represents the most
      frequent genetic cause of end-stage kidney disease in the first three decades of
      life. A 27-year-old male was presented with gait imbalance, sever pruritus since
      10 days prior time of admission. In past medical history, he had bilateral
      cataract, torsional nystagmus, and bilateral optic nerve atrophy since 2 years of
      age. He was also mentioned history of multinodular goiter with dysfunctional
      thyroid state since 2 years before admission. At admission bilateral blindness,
      torsional nystagmus, asymmetric thyromegaly with nodularity was found in physical
      examination. Laboratory tests showed elevated urea and creatinine (200, 10.7
      mg/dl), hypomagnesemia (1.1 mEq/l), decreased thyroid stimulating hormone (<0.004
      mIU/l). Ophthalmologist consultation confirmed retinitis pigmentosa. Renal
      sonography showed small-sized kidneys. Brain magnetic resonance imaging did not
      reveal molar tooth sign. Genetic testing performed and a large homozygous
      deletion at the NPHP1 gene locus was found. The patient was diagnosed with
      juvenile nephronophthisis and consideration of dysthyroidism as extrarenal
      manifestation of nephronophthisis is suggested in this case. Furthermore, loss of
      function mutation in SLC41A1 gene that leads to magnesium depletion must be noted
      in patients with suspected to nephronophthisis.

PMID- 28509139
TI  - Unusual Listeria monocytogenes peritonitis in peritoneal dialysis patient with
      liver cirrhosis: a case report and review of literature.
AB  - Spontaneous Listeria peritonitis is well described in liver failure, but is
      uncommon in peritoneal dialysis patients. Atypical cases where peritonitis
      symptoms develop after systemic manifestations are rare and challenging for
      diagnostic. A 57-year-old peritoneal dialysis patient with history of ethylic
      cirrhosis was admitted after epileptic seizure. On admission, patient was
      soporous without signs of peritonitis and meningitis. Patient's peritoneal
      effluent was clear, with normal leukocytes. Cranial CT scan showed no
      abnormalities. Laboratory exams revealed positive inflammatory syndrome. Despite
      antibiotic therapy, next day, symptoms aggravated with coma development.
      Peritoneal effluent became cloudy and its leukocyte count rose up. Effluent
      microscopy revealed Gram-positive bacilli. Patient was started with
      intraperitoneal Vancomycin and Amikacin. Patient's clinical condition
      deteriorated with lethal outcome. Post-mortem analysis of effluent and blood
      culture showed growth of L. monocytogenes. Apart from idiopathic etiology, goat
      milk curd, that patient had started consuming 10 days before admission, could
      theoretically be considered as possible infection vehicle. L. monocytogenes
      peritonitis in peritoneal dialysis patients is rare, but must be considered in
      immunocompromised or patients with concomitant liver failure, especially after
      Gram-positive bacilli identification in peritoneal effluent. In case of
      suspiscion of Listeria peritonitis, Ampicillin should be initiated, because
      bacteria often poorly respond to currently recommended empiric regimens.

PMID- 28509140
TI  - A rare adult case of poststreptococcal acute glomerulonephritis with a
      retropharyngeal abscess.
AB  - Retropharyngeal abscess is an infection involving the retropharyngeal space which
      is posterior to the pharynx and oesophagus, and it results as a complication of a
      primary infection elsewhere in the head and neck including the nasopharynx,
      paranasal sinuses, or middle ear, which drain lymph to the retropharyngeal lymph
      nodes. Their lymph nodes are prominent in children and atrophy with age.
      Therefore, retropharyngeal abscess is most frequently encountered in children,
      with 75% of cases occurring before the age of 5 years, and often in the first
      year of life. We experienced a rare adult case of poststreptococcal acute
      glomerulonephritis with a retropharyngeal abscess, and conservative therapy
      ameliorated them. According to past reports, only one child with a
      retropharyngeal abscess and poststreptococcal acute glomerulonephritis has been
      presented at a conference to date; this is the first adult case of
      poststreptococcal acute glomerulonephritis with a retropharyngeal abscess.
      Retropharyngeal abscess can be fatal including airway compression, so it is
      important to remember retropharyngeal abscess in a case of poststreptococcal
      acute glomerulonephritis with severe symptoms of neck.

PMID- 28509141
TI  - Primary Ewing sarcoma of the kidney: a case report and treatment review.
AB  - Ewing sarcomas/primitive neuroectodermal tumors (ES/PNET) of the kidney are
      rarely found high-grade malignant tumors, offering poor prognosis. Although
      established treatment guidelines for ES of kidney are scarce, a multi-modality
      treatment approached is typically implemented. Herein, we report a 14-year-old
      female patient with ES of right kidney. Post-nephrectomy disease recurrence was
      treated with chemotherapy (i.e., vincristine, doxorubicin and cyclophosphamide);
      marked reduction in tumor size (i.e., from 18.5 * 11.3 cm2 to 3.7 * 2.2 cm2; ~96%
      reduction in size) as per computed tomography images was observed. We present our
      treatment experience and review from the available literature.

PMID- 28509142
TI  - Erosion of a Tenckhoff catheter to the sigmoid colon: an uncommon delayed
      complication.
AB  - Continuous ambulatory peritoneal dialysis is one of the most commonly used
      therapies for patients with impaired renal function. Most frequent complications
      directly related to the catheter usually present within the first weeks, and
      range from catheter dysfunction to dialysis-associated peritonitis; bowel
      perforation while placing the catheter is uncommon, and it is usually assessed in
      the same surgical event. There are, however, delayed complications, and one of
      the least frequently described is erosion of the catheter into the bowel. We
      present the case of a 65-year-old man, who shows up at the emergency room
      referring to "acute diarrhea" associated with his dialysis, it is quickly
      diagnosed as a bowel perforation and underwent emergency surgery. During the
      operation we found adhesions compromising small bowel and sigmoid colon, the far
      end of the dialysis catheter inside the sigmoid colon, with no signs of colonic
      leakage to the peritoneal space. We removed the dialysis catheter, resected the
      fibrous borders of the site of insertion and performed a primary closure. The
      patient evolved satisfactorily and was subsequently discharged to continue with
      hemodialysis for renal substitution therapy.

PMID- 28509143
TI  - Anaphylactoid reaction to immunoadsorptive membrane in a patient with myasthenia
      gravis.
AB  - Extracorporeal adsorption therapy has been carried out clinically in cases of
      myasthenia gravis (MG) since the 1980s without any major complications. Despite a
      lack of clinical evidence, it has been accepted as a potential therapy for
      steroid-resistant patients in many institutes. Recently, we experienced a case of
      MG with an anaphylactoid reaction during extracorporeal immunoadsorption therapy.
      A 64 year old women with MG showed an anaphylactoid reaction immediately after
      the initiation of adsorption therapy using a polyvinylalcohol gel column. It is
      therefore important to bear in mind that extracorporeal adsorption therapy could
      trigger an anaphylactoid reaction, which may induce a MG crisis.

PMID- 28509144
TI  - A case of familial Mediterranean fever-associated systemic amyloidosis.
AB  - Familial Mediterranean fever (FMF) is a chronic inflammatory disease,
      characterized by recurrent fever and polyserositis (pleuritis and/or
      peritonitis). The most important complication of FMF is amyloidosis, which causes
      chronic renal failure. Colchicine is the most effective treatment in acute
      attacks and amyloidosis development. However, the majority of patients with
      amyloidosis have a relentless progression to end-stage renal disease despite
      initiation of colchicine treatment. We present the case of a 38-year-old man with
      FMF-associated chronic renal failure due to systemic amyloidosis. The patient
      suffered from periodic fever and renal insufficiency, and was admitted to our
      hospital. Laboratory examination revealed an inflammatory reaction, renal
      dysfunction (serum creatinine 2.5 mg/dl), and proteinuria. Renal biopsy revealed
      segmental mesangial AA amyloid deposits in several glomeruli and the walls of
      several vessels. Genetic analysis showed that the patient was heterozygous for
      the MEFV gene (E148Q/M694I). Thus, he was diagnosed with FMF, and colchicine
      treatment was initiated. He remained almost attack free, with decreasing serum
      creatinine levels (1.6 mg/dl) and diminishing urinary protein excretion. In
      conclusion, renal amyloidosis is the most important long-term complication of
      FMF, and treatment with colchicine is effective for preventing progression.
      Therefore, colchicine treatment should be initiated as early as possible after
      the diagnosis of FMF.

PMID- 28509145
TI  - Gastric bleeding reduced upon switch from haemodialysis to CAPD.

PMID- 28509146
TI  - Efficacy of tocilizumab, a humanized neutralizing antibody against interleukin-6
      receptor, in progressive renal injury associated with Castleman's disease.
AB  - Castleman's disease is a benign lymphoproliferative disorder in which interleukin
      6 (IL-6), a pleiotropic proinflammatory cytokine, is thought to play a
      pathogenetic role. Presented is the case of a 72-year-old man with Castleman's
      disease who exhibited progressive renal dysfunction with proteinuria. Renal
      biopsy revealed mesangial hypercellularity and matrix expansion in most glomeruli
      and peritubular inflammatory cell infiltration. Immunofluorescence studies showed
      intense deposition of IgG in a granular pattern along the glomerular basement
      membrane. Histological features were compatible with membranoproliferative
      glomerulonephritis accompanied by interstitial inflammatory cell infiltration.
      Immunohistological analysis showed that IL-6 was abundantly expressed by tubular
      cells and interstitial macrophages, suggesting involvement of IL-6 in the renal
      injury. As a result of administration of tocilizumab, a humanized anti-IL-6
      receptor antibody, the patient experienced clinical and biochemical improvement
      of Castleman's disease, including marked reduction of proteinuria and
      stabilization of renal function. These findings suggest the efficacy of
      tocilizumab against Castleman's disease and its renal complications.

PMID- 28509147
TI  - Granulomatous interstitial nephritis in a renal allograft.
AB  - We describe a middle-aged woman in whom granulomatous interstitial nephritis
      (GIN) developed in a renal allograft. She had undergone bowel resection due to an
      uncertain diagnosis of active granulomatous bowel disease 30 years earlier.
      Thereafter, frequent hyperoxaluria as well as calcium oxalate stone and recurrent
      urinary tract infections had resulted in a progressive deterioration in kidney
      function over a period of 20 years. She underwent living donor kidney
      transplantation; however, her kidney function progressively deteriorated, despite
      transplantation. A biopsy of the renal allograft revealed GIN with granulomatous
      vasculitis accompanied by calcium oxalate crystals. These as well as the
      laboratory findings indicated a diagnosis of sarcoidosis. We considered that the
      aggravated granulomatous inflammation on the allograft was caused by recurrent
      sarcoidosis accompanied by hyperoxaluria.

PMID- 28509148
TI  - Lupus-like glomerulonephritis: an autoimmune complication of hepatitis C
      infection.
AB  - Lupus-like glomerulnephritis in patients with negative lupus serologies and no
      extra-renal manifestations of lupus can create a diagnostic dilemma. We describe
      a 53-year-old gentleman with chronic hepatitis C virus (HCV) infection who
      presented with dialysis-requiring renal failure, renal histologic findings of
      "full-house" immunofluorescence label and tubuloreticular inclusions on
      electronic microscopy, but no extra-renal or laboratory signs of systemic lupus
      erythematosis. Attempted treatment with cyclophosphamide and corticosteroids was
      limited by cyclophosphamide hypersensitivity. The patient remained dialysis
      dependent over 18 months of observation and did not develop extra-renal clinical
      or biological manifestations of lupus. Mimics of seronegative lupus with isolated
      renal involvement can include HCV-related autoimmunity. Treatment of acute
      glomerulonephritis may be similar initially, but other concerns in patients with
      HCV infection include excluding cryoglobulinemia, the potential impact of
      immunosuppression therapy on liver disease and consideration of subsequent use of
      antiviral therapy. Given the increasing prevalence of HCV globally, the
      recognition of extra-hepatic autoimmune manifestations of HCV infection will
      likely increase.

PMID- 28509149
TI  - A case of renal hypouricemia and a G774A gene mutation causing acute renal injury
      that was improved by hemodialysis.
AB  - A 16-year-old man came to our hospital complaining of loin pain after a middle
      distance race. Following admission, his renal dysfunction worsened rapidly,
      requiring several hemodialysis sessions. A renal biopsy showed no change in the
      glomeruli, although interstitial edema was observed. Following the recovery of
      renal function, we confirmed that his uric acid level was abnormally low and
      urate clearance was abnormality high. Gene analysis showed that he had a G774A
      mutation which dominated the SLC22A12 gene encoding the urate transporter 1.

PMID- 28509150
TI  - Primary omental pleomorphic liposarcoma identified at autopsy in a living donor
      kidney transplant recipient.
AB  - Metastatic and recurrent tumors of the omentum are common, but primary omental
      pleomorphic liposarcoma (POPL) is an extremely rare type of solid omental tumor.
      We describe the case of a patient with POPL who received a renal transplant from
      a living donor. Despite good allograft function, the volume of peritoneal fluid
      gradually increased. An exploratory laparotomy could not be performed because the
      patient was obese and developed hemodynamic instability. Therefore, a shunt was
      placed between the peritoneal cavity and the internal jugular vein using the
      Denver(r) shunt system; however, the patient died of respiratory insufficiency.
      On the basis of the autopsy results, we diagnosed the patient's condition as
      POPL. We speculated that the malignancy did not originate directly from the donor
      cells. We report POPL in a living donor renal transplant recipient.

PMID- 28509151
TI  - Two cases of atypical membranoproliferative glomerulonephritis showing opposite
      clinical course.
AB  - Atypical membranoproliferative glomerulonephritis (MPGN) is considered to
      progress to typical MPGN, and it is believed that it can be treated with
      corticosteroids. However, consensus that atypical MPGN is a continuum of
      morphologic manifestations of typical MPGN cannot be reached. Herein, we report
      two cases of atypical MPGN with opposite clinical course. Case 1 was a 4-year-old
      boy with macrohematuria and proteinuria with no prodromal symptoms. His serum C3
      level had abruptly dropped, and renal biopsy confirmed a diagnosis of atypical
      MPGN. After performing kidney biopsy, his urinary abnormality improved and his C3
      level had normalized 1 year after onset without medication. At the most recent
      follow-up, neither proteinuria nor hematuria was detected. Case 2 was a 7-year
      old girl with microhematuria and proteinuria at her school urinary screening. Her
      first biopsy finding was similar to dense deposit disease, and the second biopsy
      showed atypical MPGN. Oral corticosteroids were started from this point, but
      heavy proteinuria and hypocomplementemia could not be improved sufficiently. We
      immediately performed third kidney biopsy and diagnosed typical MPGN. These
      findings suggest that the indication of therapy for atypical MPGN should be re
      examined. Aggressive therapy such as steroid administration is not necessarily
      essential and effective for therapeutic intervention of all atypical MPGN.
      Moreover, atypical MPGN may involve different etiologic and pathogenetic factors,
      rather than a continuum of morphologic manifestations of MPGN.

PMID- 28509152
TI  - Kidney transplantation during a twin pregnancy. Case report and review of the
      literature.
AB  - Kidney transplant in a pregnant woman is exceptional, with only six cases being
      reported. Pregnancy was not known at the time of the transplant in five of these
      cases. We report the case of a 26-year-old woman who was diagnosed as carrying a
      twin pregnancy 4 months after starting hemodialysis. In order to improve the
      survival chances for the twins, she underwent an orthotopic renal transplant from
      a living donor at 20 weeks of gestation. The allograft functioned immediately and
      4 weeks passed without incident. At the 26th week of gestation, the patient had a
      precipitous labor, delivering two male babies with no malformations, weighing 755
      and 890 g, who died due to respiratory failure. The allograft worked normally
      afterwards. Sixteen months later, the patient delivered a normal 37 weeks'
      gestation baby. The renal graft continued working normally for the next 20 years,
      after which signs of chronic allograft nephropathy developed. Azathioprine was
      replaced with mycophenolate mofetil. At the last evaluation, 23 years after
      transplant, the patient's serum creatinine was 2.9 mg/dl and her estimated
      glomerular filtration rate (eGFR) was 22 ml/min/1.73 m2. This unique case
      demonstrates that it is possible to perform an orthotopic kidney transplant in a
      20-week twin-gestation, with a long graft survival time.

PMID- 28509153
TI  - Morphological analysis of biofilm of peritoneal dialysis catheter in refractory
      peritonitis patient.
AB  - A 66-year-old man undergoing peritoneal dialysis (PD) was admitted to our
      hospital for treatment of PD-related peritonitis. Culture of the PD fluid
      revealed the presence of Citrobacter freundii, and therapy with ceftazidime was
      started intraperitoneally. The cell count in PD fluid slowly decreased over time
      during the first 2 weeks of treatment, but increased again on the 14th hospital
      day. A second culture of the PD fluid revealed the presence of Enterococcus
      species. A switch in antibiotic therapy to vancomycin did not improve the cell
      count in the PD fluid. A third culture of the PD fluid revealed the presence of
      Stenotrophomonas maltophilia. The PD was discontinued and the catheter removed on
      the 28th hospital day. Examination of the catheter revealed that the inner tip
      was coated with a fibrous sheet of cells, suggesting biofilm formation. Following
      catheter removal, the patient was administered intravenous ciprofloxacin, and the
      inflammatory reaction started to disappear immediately and had completely
      disappeared after 1 week of treatment. Microscopic analysis of the fibrous
      structure on the catheter revealed multiple layers of various inflammatory cells.
      Immunostaining revealed the presence of CD44-positive polynuclear cells,
      indicating neutrophils, facing the catheter lumen. CD68-positive cells,
      indicating macrophages, were observed in the following layer, and keratin
      positive cells, indicating peritoneal mesothelial cells, were present at the
      bottom of the structure. Based on the immediate improvement of PD-related
      peritonitis after catheter removal, we presumed that this biofilm contributed to
      the intractability of the patient's peritonitis. Morphological analysis of
      catheter revealed that both the mesothelial cells and the various inflammatory
      cells may have contributed to biofilm development.

PMID- 28509154
TI  - Successful treatment of icodextrin-single peritoneal dialysis for refractory
      nephrotic syndrome induced by idiopathic membranous nephropathy.
AB  - The patient was a 76-year-old male who developed nephrotic syndrome. Idiopathic
      membranous nephropathy was diagnosed by renal biopsy and clinical findings. The
      patient had been refractory to predonisolone and cyclosporine A therapies, and
      overhydration recurred repeatedly during the clinical course. One year after an
      initial hospitalization, he had to be hospitalized a second time because of
      overhydration. During the hospitalization, he underwent fluid removal by the
      extracorporeal ultrafiltration method (ECUM), as his response to diuretics was
      too weak to permit the control of cardiac insufficiency. The ECUM alleviated his
      overhydration, but no remission of nephrotic syndrome was achieved. The patient
      was then discharged temporarily, but overhydration developed again 2 months
      later. Peritoneal dialysis (PD) using an overnight dwell of a single dose of
      icodextrin was initiated to obtain stable fluid removal. This promptly alleviated
      the refractory subcutaneous edema, and type I incomplete remission of nephrotic
      syndrome was achieved about 2 weeks after the start of PD. The patient could be
      withdrawn from the PD therapy 4 months later. Subsequently, the urinary volume
      was maintained and the serum creatinine level was stabilized at about 2 mg/dl. In
      our patient, the protein leakage into the drainage was small enough to permit
      remission of the nephrotic syndrome with stable fluid removal. On this basis, we
      believe that PD using icodextrin is considered as one of the options for the
      treatment of refractory nephrotic syndrome with poor water control.

PMID- 28509155
TI  - Interaction of miconazole oral gel with warfarin and cyclosporine in a patient
      with nephrotic syndrome.
AB  - It is well known that miconazole inhibits cytochrome P450 (CYP). However, this
      drug in oral gel form is believed not to absorb into systemic circulation, and
      therefore not to inhibit CYP. We experienced a case of increased oral
      bioavailability of warfarin and cyclosporine with this gel for treatment of oral
      candidiasis in a patient with nephrotic syndrome. Her prothrombin time
      international normalized ratio (PT-INR) increased from 2 to 7.25, and the
      cyclosporine concentration at 2 h after final dosing (C2) increased from 633.8 to
      1396.5 ng/ml 6 days after the coadministration. These problems were resolved by
      termination of the gel and switching to amphotericin B gargle. We further
      detected a significant amount of miconazole in her plasma, directly showing for
      the first time in a patient with this interaction that oral miconazole gel was
      actually absorbed into systemic circulation. Because warfarin and cyclosporine
      are often used simultaneously by nephrologists, caution should be applied with
      combined use of these drugs and oral miconazole gel to avoid adverse reaction.

PMID- 28509156
TI  - BK virus-induced acute motor-axonal polyneuropathy in a renal transplant patient.
AB  - Neurological complications are not uncommon in patients with renal
      transplantation, mostly affecting the central nervous system, and less frequently
      the peripheral nerves. BK virus infection is relatively common in transplant
      recipients and in some cases may lead to neurological complications. In this
      report, we present an interesting case of a patient who developed acute axonal
      motor polyneuropathy in the course of BK virus infection 3 months after kidney
      transplantation. After BK virus clearence in blood, a significant improvement was
      noted in her polyneuropathy. In patients with acute axonal motor polyneuropathy
      after transplantation BK virus-induced polyneuropathy should be excluded.

PMID- 28509157
TI  - Extrapulmonary tuberculosis presented as fever of unknown origin in two patients
      with endstage kidney disease not on dialysis: usefulness of 18-FDG-PET/CT in the
      diagnostic localization of fever of unknown origin.
AB  - Tuberculosis is one of the common causes of fever of unknown origin in patients
      with chronic kidney disease (CKD). Extrapulmonary tuberculosis is more common in
      CKD patients, and is, unfortunately, often underdiagnosed despite extensive
      assessments. Recently, fluorine-18-deoxyglucose-positron emission
      tomography/computed tomography (FDG-PET/CT) has been available in the diagnosis
      of malignancy, inflammatory and infectious diseases, and has become a useful
      diagnostic tool. Here, we present two cases of endstage kidney disease who
      presented with fever of unknown origin at the time of dialysis initiation. In
      both cases, although interferon-gamma-releasing assay was positive, combined
      conventional diagnostic modalities such as computed tomography and gallium
      citrate scintigraphy failed to detect the sites infected with tuberculosis. By
      contrast, extrapulmonary lesions were detected by FDG-PET/CT and successfully
      treated with combined anti-tuberculous drugs. Diagnosis of extrapulmonary
      tuberculosis was confirmed by biopsy of the affected lymph node and lumbar spine,
      followed by PCR of the biopsied specimen. These cases highlight the importance of
      considering tuberculosis as one of the differential diagnoses in pre-dialysis CKD
      patients with persistent fever, and the usefulness of FDG-PET/CT in the detection
      of infectious sites of extrapulmonary tuberculosis.

PMID- 28509158
TI  - Treatment of a recurrent renal artery stenosis and stent fracture using a drug
      eluting stent in a pediatric patient.
AB  - Renal artery obstruction is uncommon in the pediatric population and therefore
      represents a challenging diagnosis to ascertain and treat. While angioplasty and
      surgery have been used to treat it, stent implantation has been left mainly for
      adult use. In the following paper, we expose the case of an 8-year-old female who
      presented with severe arterial hypertension. Initially, the patient was evaluated
      and up to 5 antihypertensive medications were started. After complete evaluation,
      she was found to have severe right renal artery distal and proximal stenosis. She
      underwent recurrent angioplasties and then a bare metal stent (BMS) implantation,
      due to recurrence of stenosis. The original BMS developed a circumferential
      fracture, leading to a second stent implant, this time using a drug eluting stent
      (DES). She has been stable for 8 years since the last intervention, although
      using 2 antihypertensive medications. The use of BMS and DES may add another tool
      in the armamentarium of the pediatric interventionist to treat these children
      with recurrent stenosis that fail angioplasty.

PMID- 28509159
TI  - Autoimmune autonomic ganglionopathy manifesting as acute-onset orthostatic
      hypotension in a patient undergoing peritoneal dialysis.
AB  - Orthostatic hypotension is an important complication in the management of
      patients receiving dialysis therapy. As for the orthostatic hypotension caused by
      decreased peripheral artery resistance, diabetic neuropathy and amyloidosis are
      the two main causes of hypotension in dialysis patients. However, some patients
      develop orthostatic hypotension that is caused by dysfunction of the autonomic
      nervous system, not by diabetic or amyloidosis-related neuropathy. We herein
      present a case of a 56-year-old man with a 17-year history of peritoneal dialysis
      therapy, who developed acute-onset orthostatic hypotension accompanied by
      hypohidrosis and erectile dysfunction. Because serum autoantibodies to ganglionic
      nicotinic acetylcholine receptor were detected, he was diagnosed with autoimmune
      autonomic ganglionopathy (AAG). He was treated with high-dose immunoglobulin
      therapy (0.6 g per kg of body weight per day) for 5 consecutive days, which
      resulted in a gradual improvement in dizziness. Two months after the onset of
      AAG, he could discontinue vasopressors (fludrocortisone acetate and midodrine
      hydrochloride) and continued maintenance dialysis therapy without the use of
      vasopressors. This case indicates that physicians should consider autonomic
      neuropathy including AAG as a differential diagnosis when they encounter dialysis
      patients with orthostatic hypotension.

PMID- 28509160
TI  - Hypersensitivity reactions to acetate in the bicarbonate dialysate in a patient
      undergoing pre-dilution online hemodiafiltration.
AB  - A 63-year-old male patient first experienced recurrent hypotensive episode during
      the dialysis session just after switching the mode from hemodialysis to online
      hemodiafiltration (OL-HDF) with infusion in pre-dilution of the bicarbonate
      dialysate containing 9.2 mEq/L of acetate. Peripheral eosinophil count and serum
      IgE were both elevated to 16,440/MUL and 2000 IU/L. The reactions promptly
      dissolved with substitution of acetate-free solution. This case illustrated that
      pre-dilution OL-HDF can induce an occult hypersensitivity to acetate in the
      standard bicarbonate dialysate.

PMID- 28509161
TI  - Use of LightCycler mutation analysis to detect type II adenine
      phosphoribosyltransferase deficiency in two patients with 2,8
      dihydroxyadeninuria.
AB  - Recently, a number of methods have been devised for detection of mutations in the
      field of molecular genetics. The LightCycler system has been used for rapid PCR,
      while simultaneously quantifying and analyzing the amplification results. We
      tried to apply the LightCycler system to detect APRT*J allele mutations in two
      families including two children with 2,8-dihydroxyadenine urolithiasis. The first
      patient was a 3-year-old girl who presented with left flank pain. The second
      patient was a 2-year-old girl who presented with complaints of sudden dysuria.
      The spectrophotometric analysis of the stone fragments of both patients revealed
      an absorption spectrum for 2,8-DHA. We used the LightCycler system to detect
      APRT*J mutation. The first patient was homozygous for APRT*J/APRT*J and the
      second patient was compound heterozygous for APRT*J/APRT*Q0. The genetic
      diagnosis of APRT deficiency using this system may be useful not only as a
      diagnostic test for infants with known 2,8-DHA, but also as a screening of
      infants with a suspicion of urolithiasis. We believed that the LightCycler system
      still is an important means of identifying APRT*J mutation.

PMID- 28509162
TI  - A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO)
      syndrome complicated by IgA nephropathy with nephrotic syndrome.
AB  - A 62-year-old man visited our hospital with a mild sore throat, high-grade fever,
      and clavicular pain. Seven years earlier, he had been diagnosed with synovitis,
      acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. His clavicles were
      tender and remarkably swollen. Also noted was marked pitting edema in the lower
      extremities and pustulosis on the palms and soles of the feet. Laboratory studies
      on admission showed an elevated white cell count (23,400/MUl) and serum C
      reactive protein level (24.4 mg/dl). Urinalysis revealed proteinuria (2+) and
      occult blood (3+) with numerous dysmorphic red blood cells and hyalin casts. The
      patient was diagnosed with recurrence of his SAPHO syndrome and started on oral
      glucocorticoid therapy. By day 9 after admission, he had gained 16 kg in body
      weight, and his proteinuria (6.4 g/day) and serum creatinine level (2.3 mg/dl)
      were elevated. Renal biopsy revealed mesangial proliferative glomerulonephritis
      with deposition of IgA and C3 in the mesangial area and along the capillary
      walls. The patient was diagnosed with IgA nephropathy accompanied by nephrotic
      syndrome. With oral prednisolone therapy, his fever, clavicular pain, and
      proteinuria were gradually relieved. The clinical course in this case suggests
      the onset of nephrotic syndrome with IgA nephropathy was associated with the
      recurrence of the patient's SAPHO. To our knowledge, this is the first reported
      case of SAPHO-associated IgA nephropathy.

PMID- 28509163
TI  - Hypokalemia-associated paralysis and metabolic acidosis in a patient with
      bilateral ureterosigmoidostomy.
AB  - Ureterosigmoidostomy is a urological intervention performed to treat various
      conditions such as invasive bladder cancer, bladder exstrophy, vesicovaginal
      fistula, or urethral trauma. However, this intervention may lead to several
      metabolic complications. Here, we report an interesting case with quadriparesis
      and intestinal paralysis resulting from severe hypokalemia (the serum potassium
      level, 1.8 mEq/L) and hyperchloremic metabolic acidosis [pH 6.927 and the
      arterial bicarbonate level, 8.0 mEq/L] in a 65-year-old man who had undergone
      bilateral ureterosigmoidostomy for bladder cancer 16 years earlier. The abdominal
      computed tomography scan also showed that massive fluid consisting of the mixture
      of the diverted urinary stream and feces was accumulated in the dilated distal
      colon. The treatment with intravenous potassium and sodium bicarbonate
      administration combined with the drainage of the diverted urinary stream from the
      distal colon resulted in the restoration of hypokalemia and acidosis followed by
      the improvement of quadriparesis and intestinal paralysis. The underlying
      mechanism and the treatment of metabolic complications after ureterosigmoidostomy
      are briefly discussed.

PMID- 28509164
TI  - Familial Mediterranean Fever developing in a Japanese kidney transplant
      recipient.
AB  - Familial Mediterranean Fever (FMF) is an auto-inflammatory disease characterized
      by periodic febrile episodes and sterile polyserositis and is extremely rare in
      Asian populations. Here, we report a case of FMF in a 61-year-old Japanese man
      who received a kidney transplant 31 years ago but had to re-start hemodialysis.
      Although kidney function had been stable since his initial transplant, serum
      creatinine levels had been increasing over the 2 years prior to his presentation
      at our hospital, and a periodic fever developed at the same time. Uremic symptoms
      were observed, and hemodialysis was re-started, prompting the patient to choose
      to undergo a second kidney transplantation. We re-checked his medical history and
      conducted further physical examinations. Given that the patient had previously
      undergone an operation for olecranon bursitis in which pericardial effusion had
      been identified, we considered the possibility of FMF and conducted a genetic
      test, which identified the E202Q heterozygous mutation in the MEFV gene. The
      patient was therefore diagnosed with variant FMF. To our knowledge, this is the
      first report of a Japanese kidney transplant recipient being diagnosed as an FMF
      variant. We describe the relationship of FMF and kidney transplantation in terms
      of prognosis and important points to note for treatment.

PMID- 28509165
TI  - Fraternal twins with job's syndrome and immune complex nephritis.
AB  - Job's syndrome or autosomal dominant hyperimmunoglobulin E syndrome (Hyper-IgE)
      is a rare disorder that results from a STAT3 gene mutation, which results in the
      absence of T-helper 17 (Th17) cells and manifests as a severe immunodeficiency.
      Affected individuals suffer recurrent soft tissue and pulmonary infections among
      other manifestations, and the spectrum of the disease is still being
      characterized. We describe 2 sisters with Job's syndrome each with variable
      expressivity. However, both patients developed proteinuric kidney disease and had
      biopsies confirming the presence of immune complex glomerulonephritis with
      staining for immunoglobulins and complement components. Previous reports link
      Job's syndrome and the development of systemic lupus erythematosus (SLE), but
      proliferative immune complex glomerulonephritis has not been described. We
      speculate that continual internal and external antigen exposure may induce an
      autoimmune process similar to SLE, which in turn may account for the immune
      complex disease in the kidney.

PMID- 28509166
TI  - Rhabdomyolysis as the first manifestation of human immunodeficiency virus
      infection.
AB  - Renal tubular acidosis (RTA) is a known complication of anti-retroviral
      medications. The presence of RTA in treatment naive-HIV patients is rare. A 49
      year-old Caucasian woman presented with recurrent non-anion gap metabolic
      acidosis, AKI, rhabdomyolysis and hypokalemia on several occasions. Diagnosis of
      acquired distal RTA due to HIV was made given the history and laboratory data. To
      the best of our knowledge, this is the first case of HIV diagnosed with an
      initial presentation of rhabdomyolysis. We believe that acute renal failure was
      due to hypokalemia precipitating rhabdomyolysis caused by HIV-induced dRTA which
      was further exacerbated by amphetamine use.

PMID- 28509167
TI  - An autopsy case of vertebrobasilar dolichoectasia under hemodialysis due to
      autosomal dominant polycystic kidney disease.
AB  - A 60-year-old male with end-stage kidney disease due to autosomal polycystic
      kidney disease began maintenance hemodialysis in 2005. A brain CT scan showed
      dilatation of left vertebral artery, basilar artery, bilateral post cerebral
      artery, and middle cerebral artery. At the time, he was diagnosed as
      vertebrobasilar dolichoectasia. He was once admitted to our hospital for ischemic
      stroke. After discharge, he was treated with anticoagulant agent from 2010 to
      2012 without any new stroke events. In March, 2012, he was admitted to our
      hospital for an evaluation of diplopia and left hemiplegia. Brain MRI showed
      acute ischemia of bilateral pons and right temporal lobe. He was once recovered
      with urokinase and argatroban, but 3 months after admission, he died with sudden
      hypotension and impaired consciousness. Autopsy revealed that subarachnoid
      hemorrhage due to the rupture of basilar artery aneurysm was responsible for this
      event.

PMID- 28509168
TI  - Immune thrombocytopenic purpura masking the fatal potential of calciphylaxis in a
      haemodialysis patient.
AB  - Calciphylaxis on the background of immune thrombocytopenic purpura (ITP) has
      never been described. The pathogenesis of calciphylaxis is complex and not fully
      understood as yet. ITP has a complex pathogenesis that leads to bleeding or
      thrombotic events. Although ITP is treatable and reversible, calciphylaxis on the
      other hand, responds poorly to treatment and carries high mortality and
      morbidity. We present a case of a 56-year-old lady with end-stage renal disease
      with ITP, who complained of 1-month history of painful necrotic patches over the
      thighs. Due to delayed diagnosis, the patient deteriorated and passed away
      despite aggressive multidisciplinary approach. This case highlights the
      importance of early recognition of the increased thrombotic risk in an end-stage
      renal failure patient with poor phosphate control and ITP.

PMID- 28509170
TI  - Cystinuria in a patient with 19q12q13.1 deletion.
AB  - Cystinuria is a genetic cause of kidney stones with a prevalence of 1 in 7000
      births. So far, two genes have been described responsible for this disorder
      (SLC3A1 and SLC7A9). We report a patient with an SLC7A9 gene mutation located in
      19q13.1 on one allele and with a 19q12q13 region deletion on the other allele.
      The characteristic clinical features of the 19q13.1 microdeletion syndrome
      include facial dysmorphism, signs of ectodermal dysplasia, growth retardation,
      neurologic features and genitourinary anomalies. Cystinuria has not yet been
      described as part of this syndrome, although one of its responsible genes
      (SLC7A9) is in the same genomic location. The index case is a 6-year-old male
      presented with distinctive facial features, cutis aplasia of the scalp,
      rudimentary teeth, microcephaly, intrauterine and postnatal growth retardation,
      psychomotor developmental delay, speech delay, epilepsy, inguinal hernias and
      cystinuria. An array-CGH analysis was performed, finding a large deletion of the
      19q12q13.11 cytobands, which affects 19 genes. Two of them are involved in the
      19q13.11 deletion syndrome and another affected gene is SLC7A9, responsible for
      type B cystinuria. Sanger sequencing was performed as well, detecting a
      heterozygous mutation of the SLC7A9 gene, located in 19q13.1. As far as we know,
      this is the first described case of cystinuria in a patient with SLC7A9 gene
      mutation located in 19q13.1 on one allele and with 19q12q13 region deletion on
      the other allele. Although this patient can be classified as a type B
      heterozygote and, therefore, his renal prognosis is not severe, the occasional
      nephrolithiasis found in such patients justifies a close follow-up with regular
      testing of urinary cystine excretion. We suggest that the recessive behavior of
      this case, explains the clinical features regarding cystinuria. We propose that
      in the face of patients affected of a phenotype matchable with 19q13.11 syndrome
      and cystinuria, a mutational or sequencing study of the SLC7A9 gene should be
      performed to allow an early onset of diagnosis and treatment.

PMID- 28509169
TI  - Successful treatment of a hemodialyzed patient with pure red cell aplasia
      associated with epoetin beta pegol therapy with cyclosporine.
AB  - A 42-year-old man with end-stage renal failure had been receiving hemodialysis
      therapy since April 2009. Initially, darbepoetin alfa was administered to treat
      his renal anemia. After treatment was switched to epoetin beta pegol, the
      patient's hemoglobin levels rapidly decreased. He was diagnosed with pure red
      cell aplasia (PRCA) based on the results of a bone marrow examination. Epoetin
      beta pegol was strongly suspected to be the cause of the PRCA, and although he
      tested negative for anti-epoetin beta pegol antibodies, epoetin beta pegol was
      discontinued and cyclosporine therapy was initiated. Thereafter, his hemoglobin
      levels increased, and his anemia dramatically improved after 3 months.

PMID- 28509171
TI  - Nephrotic syndrome after scorpion sting.
AB  - Scorpion venom is a water soluble, antigenic and heterogeneous mixture. The venom
      is composed of varying concentration of neurotoxin, cardiotoxin, nephrotoxin,
      haemolytic toxin, phosphodiesterase, phospholipases, hyaluronidases,
      glycosaminoglycans, histamine, serotonins, and tryptophan and cytokine releasers.
      The reported incidence of scorpion sting in India is 0.6 %. Scorpion sting
      resulting in acute renal failure has been reported in the past, but not the
      nephrotic syndrome. We report a patient of nephrotic syndrome after scorpion
      sting. The lacunae in the present knowledge linking scorpion sting venom with
      nephrotic syndrome would only be replete with publications of similar reports.

PMID- 28509172
TI  - A case of primary adrenal diffuse large B cell lymphoma presenting with severe
      hyponatremia.
AB  - We herein report a case of primary adrenal lymphoma with severe hyponatremia. The
      patient was admitted for an evaluation of severe hyponatremia and an enlarged
      bilateral adrenal mass, which were found in a previous examination for causes of
      general fatigue and anorexia. Laboratory data, including the serum levels of
      sodium (115 mEq/L), osmolality (239 mOsm/kgH2O), ADH (5.8 pg/mL), cortisol (11.6
      MUg/dL), free T3 (2.42 pg/mL), urinary Na (117 mEq/L) and urine osmolality (490
      mOsm/kgH2O), fulfilled the diagnostic criteria for the syndrome of inappropriate
      secretion of ADH (SIADH). An abdominal computed tomography scan revealed a large
      bilateral adrenal mass. A biopsy of the enlarged left adrenal mass revealed
      diffuse large B cell lymphoma, which was negative for ADH protein. Hydrocortisone
      treatment normalized the patient's body temperature and serum sodium
      concentration. In this case, hyponatremia developed when both adrenal glands were
      involved and was normalized with hydrocortisone. These findings suggest that
      adrenal insufficiency was the cause of hyponatremia, although the basal serum
      cortisol was normal. The current case suggests that the administration of
      hydrocortisone is recommended if suspicious clinical signs or symptoms are found
      in severe hyponatremia, even if hyponatremia is associated with a normal serum
      cortisol level and fulfills the diagnostic criteria for SIADH.

PMID- 28509173
TI  - A case of minimal change nephrotic syndrome with hypothyroidism deterioration.
AB  - A 73-year-old woman with Graves' disease underwent total thyroidectomy and was
      being treated with levothyroxine. She developed edema in the lower region of both
      legs 1 month before hospitalization. She had a high concentration of urine
      protein and was hospitalized for further assessment. A urine protein
      concentration of 4.4 g/day was observed, and she was diagnosed with minimal
      change nephrotic syndrome (MCNS) after kidney biopsy. The patient's thyroid
      function had declined, as indicated by a thyroid-stimulating hormone (TSH) level
      of 139.0 MUIU/mL and a free thyroxine (fT4) level of 0.66 ng/dL. She was
      prescribed 40 mg/day of prednisolone (PSL) and achieved remission. fT4 level
      normalized on the 36th hospital day. She was in remission subsequently. However,
      MCNS recurred when PSL was tapered to 10 mg/day. When she was rehospitalized,
      thyroid function decline was noted once more, with a TSH level of 29.8 MUIU/mL
      and an fT4 level of 0.74 ng/dL. Her oral PSL dose was increased to 30 mg/day, but
      she did not achieve remission. However, she achieved remission after steroid
      pulse therapy. After remission, the thyroid function normalized. During the
      course of her treatment, the levothyroxine dose was maintained at 87.5 MUg/day.
      Therefore, we predicted that the loss of thyroid hormone in urine due to
      nephrotic syndrome may have led to the aggravation of hypothyroidism. We have
      reported this case because of its rarity.

PMID- 28509175
TI  - List of referees.

PMID- 28509174
TI  - De novo papillary carcinoma in a renal allograft: the pros and cons of
      immunosuppression.
AB  - We present a case of a multifocal kidney transplant renal cell carcinoma in a 35
      year-old lady, presenting 16 years after kidney transplantation, diagnosed during
      investigation of recurrent urinary tract infections. The patient underwent a
      graft nephrectomy and subsequently maintained on haemodialysis. She remained
      disease-free after 4 years of surveillance and thus reactivated on the transplant
      list. This case reinforces the fact that immunosuppressive therapy has made
      kidney transplantation possible; however, it is accompanied by a higher incidence
      of malignancy. It also reinforces the importance of lifelong screening of both
      native and renal transplant grafts.

PMID- 28509177
TI  - Karyomegalic interstitial nephritis.
AB  - Karyomegalic interstitial nephritis is a singular type of progressive chronic
      interstitial nephritis. The pathogenesis of this disease is unknown. The present
      study reported the case of a 22-year-old man who presented with a long history of
      recurrent upper respiratory tract infection episodes secondary to bronchiectasis
      and with progressive renal failure. Renal biopsy revealed chronic
      tubulointerstitial nephritis and a surprisingly marked karyomegaly specifically
      of the tubular epithelium.

PMID- 28509176
TI  - Two autosomal dominant polycystic kidney (ADPKD) cases with advanced renal
      dysfunction, effectively treated with tolvaptan.
AB  - We report here two cases of autosomal dominant polycystic kidney disease (ADPKD)
      with renal dysfunction that were treated with tolvaptan. Case 1 was a 47-year-old
      man with a glomerular filtration rate (GFR) of 17.0 ml/min/1.73 m2 who received
      tolvaptan treatment (30 mg/day). After treatment, kidney pain was alleviated, and
      the estimated GFR (eGFR) decline improved from -9.84 ml/min/1.73 m2 per year to 
      4.08 ml/min/1.73 m2 per year, respectively. The rate of increase in total kidney
      volume was reduced from 18 % per year before treatment to 4 % per year following
      tolvaptan administration. Case 2 was a 44-year-old man with a GFR of 22.6
      ml/min/1.73 m2, and the eGFR decline improved from -5.76 ml/min/1.73 m2 per year
      before treatment to -3.12 ml/min/1.73 m2 per year following tolvaptan treatment
      (30 mg/day). The rate of increase in total kidney volume was also decreased from
      10 % per year before treatment to -7 % per year following tolvaptan
      administration. These results suggested that tolvaptan may be effective in
      impeding kidney function aggravation and kidney volume increase in ADPKD patients
      with advanced renal dysfunction.

PMID- 28509178
TI  - Carbonic anhydrase II deficiency: report of a novel mutation.
AB  - Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder
      characterized by renal tubular acidosis, osteopetrosis, recurrent bone fractures,
      renal stones, growth failure, and mental retardation. Several cases have been
      reported in Saudi Arabia with homozygous mutations in CA2 consistent with a high
      degree of consanguinity. We report a case of carbonic anhydrase II deficiency
      with short stature, mixed renal tubular acidosis, recurrent bone fractures due to
      trivial trauma, recurrent renal stones and cerebral calcification. This patient
      was compound heterozygous for a novel CA2 mutation and a previously reported
      mutation in Arabs.

PMID- 28509180
TI  - A case of histopathologically confirmed infective endocarditis with no
      vegetations observed during preoperative diagnosis.
AB  - An 81-year-old woman on maintenance hemodialysis (HD) was admitted to the
      hospital with fever and repeated positive blood cultures for coagulase-negative
      staphylococci. The patient had a history of aortic valve replacement for aortic
      valve stenosis (AS). Although one major criterion and two minor criteria from the
      Duke criteria were met and therefore infective endocarditis (IE) was suspected
      for this case, no definitive diagnosis was made. Vegetations were not observed on
      the transesophageal echocardiography, but AS was prominent. The patient was
      refractory to antibiotic therapy using vancomycin, and blood cultures did not
      convert to negative. To treat the suspected IE and AS, aortic valve replacement
      was performed. Although vegetations were not observed in the resected valve, gram
      positive cocci were found in clusters, and a histopathological diagnosis of IE
      was made. The postoperative blood culture converted from positive to negative,
      and the patient was subsequently discharged from the hospital. While relative
      risk of IE is high in HD patients, a definitive diagnosis of IE may be difficult
      due to calcification of the valve and valve replacement. In HD patients with
      bacteremia, suspicion of IE should be aggressively pursued if other sources of
      infections are negative, and if the patient is refractory to medical treatment,
      surgical treatment may be necessary.

PMID- 28509179
TI  - Acute interstitial nephritis with membranous nephropathy in bucillamine-treated
      rheumatoid arthritis.
AB  - In bucillamine-treated patients, persistent proteinuria caused by membranous
      nephropathy (MN) is a major adverse effect affecting the kidneys. We experienced
      a case of acute interstitial nephritis (AIN) with MN caused by bucillamine. An 81
      year-old Japanese woman with a past medical history of rheumatoid arthritis and
      hypertension presented with a fever, epigastric pain, and nausea of 1 week's
      duration. She had commenced bucillamine 4 months earlier. At the time of
      admission, her baseline creatinine (0.8 mg/dl) had risen to 6.8 mg/dl. A renal
      biopsy revealed AIN with concomitant MN. Renal function gradually improved after
      bucillamine administration was stopped. In addition to MN, bucillamine can cause
      AIN, which requires a renal biopsy for definitive diagnosis. Given the host of
      pathological findings that tend to develop in patients using bucillamine,
      patients receiving the drug who present with symptoms of acute kidney injury
      should undergo a renal biopsy to determine the presence of AIN.

PMID- 28509181
TI  - Use of darbepoetin alfa for myelodysplastic syndrome coincident with chronic
      kidney disease.

PMID- 28509182
TI  - Subacute pulmonary embolism in a hemodialysis patient, successfully treated with
      surgical thrombectomy.
AB  - A 53-year-old woman was admitted to our hospital with a 1-month history of
      gradually progressive resting dyspnea and lumbar backache. For the preceding 6
      years, she had received regular hemodialysis for end-stage renal disease caused
      by autosomal dominant polycystic kidney disease and had taken tamoxifen for 3
      years as post-operative chemotherapy for breast cancer. Before admission, the
      patient's symptoms had been attributed to volume overload, based on right
      thoracic fluid and leg edema. However, despite volume correction by dialysis
      therapy, her symptoms had not improved. The patient was transferred to our
      hospital, where she was diagnosed with subacute pulmonary embolism (PE). Emergent
      pulmonary thrombectomy was performed using cardio-pulmonary bypass. The patient
      was discharged from our hospital on post-operative day 23. Recent reports have
      shown that hemodialysis patients have a relatively higher risk of PE compared
      with the general population. Our case had additional risk factors for PE: female
      sex, decreased protein C level, tamoxifen use, and autosomal dominant polycystic
      kidney disease. These factors may have had a synergistic effect on the onset of
      PE.

PMID- 28509183
TI  - Single low-dose rituximab for the treatment of steroid-resistant nephrotic
      syndrome with acute kidney injury.
AB  - The efficacy of rituximab for kidney disease, such as frequent relapsing
      nephrotic syndrome, has been reported recently. Herein, we report a case of a
      patient with acute kidney injury that was steroid-resistant nephrotic syndrome
      who responded to a single administration of low-dose rituximab. An 86-year-old
      Japanese woman with hypertension presented with severe peripheral edema within
      several days after onset. Due to the patient's age, renal biopsy was not
      performed, nephrotic syndrome was diagnosed and prednisolone was administered at
      40 mg/day on the day after admission. However, anuria developed and hemodialysis
      was inevitably initiated on the 5th hospital day. The renal function did not
      recover, and the general condition gradually became aggravated. On the 50th
      hospital day, 100 mg rituximab was administered, which led to immediate depletion
      of CD20-positive cells. The urine volume gradually increased from 2-3 weeks after
      the rituximab administration, and the renal function recovered slightly. After 5
      weeks, it became possible to wean the patient from dialysis, which had been
      applied for 3 months. Rituximab might be an option for the treatment of acute
      kidney injury due to steroid-resistant nephrotic syndrome.

PMID- 28509184
TI  - Mizoribine-induced severe hyperglycemia in a patient with microscopic
      polyangiitis.
AB  - A 77-year-old woman had been receiving prednisolone (PSL) for 5 months as
      induction therapy for microscopic polyangiitis. Because of repeated elevation of
      the antineutrophil cytoplasmic autoantibody titer, we added mizoribine (MZR),
      and, 2 months later, the patient developed severe hyperglycemia with low serum
      and urinary C-peptide reactivity (CPR). The MZR was, therefore, withdrawn and
      insulin therapy was started. One month later, the serum and urinary CPR had
      increased and postprandial hyperglycemia had improved. Previous in vitro studies
      have shown that MZR can induce hyperglycemia through at least two mechanisms. One
      is the alteration of insulin secretion from islet cells, and the other is action
      via the glucocorticoid receptor (GR). MZR reduces insulin secretion through the
      depletion of intracellular guanosine triphosphate (GTP), which leads to the
      inhibition of mitogenesis and induction of beta cell apoptosis. MZR affects
      insulin resistance by activating the GR through interaction with the 14-3-3
      protein, leading to postprandial hyperglycemia. Although postprandial
      hyperglycemia generally appears between 3 and 7 weeks after PSL administration,
      that in our patient did not become apparent during 5 months of PSL monotherapy,
      but was manifested 2 months after the introduction of MZR, and improved after MZR
      had been withdrawn. We conclude from these findings that MZR had been responsible
      for the hyperglycemia in our patient.

PMID- 28509185
TI  - A case of bacterial peritonitis caused by Roseomonas mucosa in a patient
      undergoing continuous ambulatory peritoneal dialysis.
AB  - Bacterial peritonitis remains a life-threatening complication of peritoneal
      dialysis (PD). Roseomonas is a bacterial genus of pink-pigmented, oxidized, gram
      negative coccobacilli that was first named in 1993. Importantly, Roseomonas
      mucosa exhibits antibiotic resistance, with significant resistance to
      cephalosporin, which is often selected as an empirical antibiotic regimen for
      peritonitis in PD patients. We herein report the case of a PD patient with
      bacterial peritonitis caused by Roseomonas mucosa that was fortunately identified
      using 16S rRNA gene sequencing and successfully treated with ciprofloxacin. Given
      that Roseomonas demonstrates resistance to a variety of antibiotics. The
      administration of empiric antibiotic therapy based on the recommendation of the
      International Society of Peritoneal Dialysis guidelines occasionally fails,
      leading to the aggravation of bacterial peritonitis. Hence, nephrologists should
      consider Roseomonas as one of the potential causative organisms of peritonitis,
      especially when gram-negative bacilli are resistant to cephalosporin and cannot
      be identified using standard laboratory methods.

PMID- 28509186
TI  - A case of adult Dent disease in Japan with advanced chronic kidney disease.
AB  - Dent disease is an inherited tubulopathy caused by a mutation in the CLCN5
      chloride channel gene. In cases of Dent disease in Japan (Japanese Dent, J-Dent),
      renal function is generally preserved and rarely progresses to advanced kidney
      dysfunction. However, the long-term prognosis of J-Dent remains unknown. We
      report the case of a 32-year-old man with J-Dent who developed advanced kidney
      dysfunction. Since the age of 3 years, he persistently exhibited proteinuria, and
      examination of a kidney biopsy specimen indicated focal segmental
      glomerulosclerosis (FSGS)-like lesions. Repeated corticosteroid treatments were
      found to be ineffective. After the age of 18 years, the patient was lost to
      follow-up and treatment was discontinued. The patient presented to our hospital
      again at the age of 32 years with advanced kidney dysfunction with low-molecular
      weight proteinuria (LMWP), along with proximal tubular dysfunction and
      nephrocalcinosis. The patient's 5-year-old nephew was also found to have LMWP
      from the age of 7 months. Therefore, Dent disease was suspected and genetic
      testing in the patient and his nephew revealed a CLCN5 mutation. Our case report
      suggests that J-Dent may cause advanced kidney dysfunction in adulthood, and,
      therefore, close collaboration between pediatricians and nephrologists is
      essential for the early identification of this complication. When male patients
      exhibit chronic kidney disease (CKD) of unknown etiology along with proximal
      tubular dysfunction and nephrocalcinosis, Dent disease should be considered.
      Investigations of undiagnosed adult J-Dent cases and further research on the
      natural history of J-Dent will help us better understand its clinical
      characteristics, prognosis, and effective treatment options.

PMID- 28509187
TI  - Recurrent proliferative glomerulonephritis with monoclonal immunoglobulin G
      deposits leads to rapid graft loss after kidney transplantation: a case report.
AB  - We present a case of recurrent proliferative glomerulonephritis with monoclonal
      immunoglobulin G (IgG) deposits (PGNMID) that progressed rapidly to allograft
      failure. A 56-year-old man had progressed to end-stage renal failure within 1
      year after the diagnosis of membranoproliferative glomerulonephritis (MPGN) by
      kidney biopsy. He underwent living donor kidney transplantation from his brother
      6 months later. Serial allograft biopsies revealed early glomerular deposition of
      IgG, C1q, and C3 at post-operative day 26, and gradual progression of the
      glomerular deposition and histology of glomerulonephritis. Several
      immunosuppressive therapies did not prevent proteinuria, microhematuria, and
      graft dysfunction, and the patient returned to hemodialysis at 7 months after
      transplantation. Retrospectively, we demonstrated monoclonal IgG3kappa deposition
      in the native and allograft kidney, and the patient was diagnosed with recurrent
      PGNMID. The serial graft biopsies revealed the pathological details of the
      progression of PGNMID. This is a rare case of PGNMID that recurred and progressed
      rapidly to graft failure after kidney transplantation.

PMID- 28509188
TI  - Atypical triad of IgA nephropathy: reversible acute kidney injury, gross
      hematuria, and severe bilateral flank pain.
AB  - Reversible acute kidney injury very rarely complicates the course of
      immunoglobulin A (IgA) nephropathy. We report an atypical case of reversible
      acute kidney injury, gross hematuria, and severe bilateral flank pain as the
      presenting triad of IgA nephropathy. Renal biopsy revealed mesangial IgA
      deposition without glomerular crescents. The patient's renal dysfunction,
      mediated by red cell tubular obstruction, interstitial nephritis, and tubular
      necrosis, resolved without intervention. We conclude that IgA nephropathy should
      be considered in the differential diagnosis for transient acute kidney injury
      with gross hematuria, and should be appropriately treated based on known
      prognostic factors.

PMID- 28509189
TI  - The importance of medical interview with CKD patient in diagnoses of a family
      with Fabry disease.
AB  - A 47-year-old Japanese man was admitted to our hospital for evaluation of
      proteinuria, which was detected when he was 37 years of age. His creatinine
      clearance levels had fallen to 76.3 mL/min/1.73 m2. A kidney biopsy was
      conducted, and the patient's low plasma alpha-galactosidase A levels suggested
      Fabry disease. After genetic counseling, GLA analysis revealed a novel mutation
      p.L387P. Interview with the patient revealed that both his younger brother and
      mother suffered from cardiomyopathy and were undergoing cardiological treatment.
      They also were positive for proteinuria. About 30 years ago, the patient's cousin
      (aged 25) was diagnosed with Fabry disease. He underwent hemodialysis for 9 years
      until his death at 42. At that time, the patient and his brother had not been
      investigated for Fabry disease so their cousin could not act as a proband for the
      brothers. Eventually, the patient, his mother, and his brother were put on enzyme
      replacement therapy with agalsidase beta. As this series of cases shows, medical
      interviews to collate both medical and family history were essential for the
      discovery of Fabry disease in these patients. In addition, being a treatable
      genetic disorder, Fabry disease should be listed in the standard differential
      diagnoses of systemic and familial diseases, including unknown cause of
      nephropathy or cardiomyopathy, for early detection of the disorder.

PMID- 28509190
TI  - Tophaceous pseudogout in a patient undergoing peritoneal dialysis.
AB  - Calcium pyrophosphate dihydrate deposition disease (pseudogout) is a crystal
      arthritis characterized by pyrophosphate dihydrate crystal deposition in the
      articular cartilage or synovium. In chronic kidney disease patients, the major
      causes of crystal arthritis are calcium oxalate crystals and basic calcium
      phosphate crystals. However, pseudogout is apparently infrequent among such
      patients. This report describes a rare case of tophaceous pseudogout (tumoral
      form of pseudogout) involving the hip joint in a peritoneal dialysis patient, as
      revealed by CT scan and synovial fluid aspiration. Fluid aspiration and oral
      NSAIDs improved the clinical symptoms. This report is the first to describe
      tophaceous pseudogout in a peritoneal dialysis patient, which suggests that
      pseudogout should be suspected in dialysis patients with unexplained arthritis.

PMID- 28509191
TI  - Probable light- and heavy-chain deposition disease in a patient with nodular
      diabetic glomerulosclerosis.
AB  - We report a case of probable light- and heavy-chain deposition disease (LHCDD) in
      a diabetic patient, a rare and educational case. The patient was a 71-year-old
      man having a long history of uncontrolled diabetes mellitus with retinopathy. He
      showed heavy proteinuria and renal insufficiency, and did not have paraproteins.
      Renal biopsy revealed nodular glomerulosclerosis with severe mesangial widening
      and microaneurysm. Immunofluorescence (IF) showed weak staining of kappa light
      chain, IgG and C1q along glomerular basement membrane (GBM). At first, we
      interpreted these IF findings to be nonspecific, thus we diagnosed as diabetic
      nodular glomerulosclerosis. Later, we recognized one of a few case reports of
      monoclonal immunoglobulin deposition disease (MIDD) in diabetic patients, and
      reconsidered the first diagnosis. The added electron microscopy (EM) showed
      obvious electron-dense materials in GBM, while tubular basement membrane deposits
      were not identified. A concurrence of LHCDD and diabetic nodular
      glomerulosclerosis may be suggested in this case. Like this case, IF staining in
      MIDD is often weak, so it is difficult to diagnose MIDD accurately without EM.
      Reports of MIDD in diabetic patients are extremely rare, possibly due to being
      often overlooked. This case emphasizes that overall pathological examination
      including IF and EM is important for the accurate differentiation of nodular
      glomerulosclerosis, even in diabetic patients.

PMID- 28509192
TI  - Two cases of minor glomerular abnormalities with proteinuria disproportionate to
      the degree of hypoproteinemia.
AB  - We experienced two female cases of minor glomerular abnormalities with
      proteinuria disproportionate to the degree of hypoproteinemia. They did not have
      adequately large amounts of urine protein so as to cause nephrotic syndrome;
      however, we were unable to determine any cause of hypoproteinemia other than
      proteinuria. The renal pathology revealed foot process effacement, and hyaline
      droplet degeneration, suggesting urine protein hyper-reabsorption in the proximal
      convoluted tubule. Therefore, we thought these cases involved pathophysiological
      conditions, such as minimal change nephrotic syndrome. In both cases, the
      hypoproteinemia improved following the administration of oral prednisolone. As in
      past reports, it is thought that the principal causative factor of
      hypoalbuminemia in patients with nephrotic syndrome is a catabolic reaction after
      the serum albumin filtered at the glomerulus is reabsorbed in the proximal
      tubule. In the present two cases, it is supposed that a large amount of urine
      protein was filtered in the primitive urine; however, the amount of final urinary
      protein did not reach the nephrotic range because most of it was reabsorbed in
      the proximal tubule and reabsorbed in the blood after being disintegrated into
      amino acids by a catabolic reaction. Or we might simply observe the process
      before the case 1 got nephrotic syndrome and the healing process of nephrotic
      syndrome in the case 2.

PMID- 28509193
TI  - Acute severe liver dysfunction induced by febuxostat in a patient undergoing
      hemodialysis.
AB  - A 58-year-old man with chronic kidney disease (CKD) was admitted to our hospital
      for hemodialysis (HD) therapy. He had been administered allopurinol (100 mg/day)
      before hospitalization, and we replaced it with febuxostat (10 mg/day), a new
      xanthine oxidase inhibitor. Levels of aspartate aminotransferase, alanine
      transaminase (ALT), and lactate dehydrogenase were within the normal ranges in
      the morning before febuxostat administration, but 6 h after administration, these
      parameters increased markedly to approximately 10 times the levels before
      administration. Although we stopped administering febuxostat, his serum potassium
      levels increased at a rate of 1 mmol/L every 12 h, and he had to undergo HD daily
      to lower the serum potassium levels. The levels of liver function test parameters
      peaked on the fourth hospital day (ALT, 1134 IU/L; AST, 1485 IU/L; and LDH, 1869
      IU/L) and recovered to normal ranges on the 13th hospital day. In this case,
      febuxostat appeared to have a relationship with acute liver dysfunction in the
      clinical course. Therefore, it would be important to check liver function test
      parameters frequently after febuxostat initiation and also to initiate a lower
      than usual dose of febuxostat, especially in patients with CKD and those who are
      undergoing HD.

PMID- 28509194
TI  - Recurrent IgA nephropathy complicated with Crohn's disease after renal
      transplantation.
AB  - A 27-year-old man was diagnosed with IgA nephropathy and Crohn's disease. He had
      been diagnosed with proteinuria and hematuria since he was 20 years old. Diarrhea
      had been a continuing problem during the past 5 months. Neither corticosteroid
      therapy nor tonsillectomy was performed. Hemodialysis was required at age of 30,
      while the symptoms of Crohn's disease were ameliorated by an elemental diet. He
      received a renal transplant from his mother 4 months after starting dialysis
      therapy. The initial immunosuppression therapy consisted of methylprednisolone,
      mycofenolate mofetil, cyclosporine, and basiliximab. Eight months after
      transplantation, proteinuria and hematuria appeared and serum creatinine was 1.4
      mg/dL. Relapse of IgA nephropathy was confirmed by the one-year protocol biopsy.
      He had suffered from tonsillitis at 32 months after the transplantation. Urinary
      protein increased to 3 g/day and serum creatinine was elevated to 2.04 mg/dL.
      Renal biopsy was performed 2 weeks after the urinary findings were aggravated.
      The cellular crescents constituted 36 % of the glomeruli. The findings of
      rejection were not confirmed in both biopsies. Tonsillectomy was performed
      thereafter. No additional immunosuppressive therapy was added. Proteinuria and
      hematuria disappeared at 4 and 20 months, respectively, after tonsillectomy, even
      when the symptoms of Crohn's disease worsened 69 months and 89 months after
      transplantation. A renal biopsy was performed 101 months after transplantation.
      Although IgA in the mesangium area was confirmed by immunohistochemical staining,
      no active lesion was seen. Tonsillectomy along with immunosuppressants for the
      graft might be an effective treatment for some patients with active recurrent IgA
      nephropathy.

PMID- 28509195
TI  - Mixed cryoglobulinemia and secondary membranoproliferative glomerulonephritis
      associated with ehrlichiosis.
AB  - Ehrlichiosis is a tick-borne disease with diverse clinical presentations, ranging
      in severity from a flu-like illness with fever and myalgias to a serious systemic
      disease with multisystem organ failure. Nephrotic syndrome has been reported
      previously in two cases of human ehrlichiosis. A kidney biopsy revealed minimal
      change disease in one of those patients. Herein, we present the case of a 40-year
      old man with ehrlichiosis who developed nephrotic syndrome, cryoglobulinemia, and
      secondary membranoproliferative glomerulonephritis (MPGN). The patient originally
      presented with shortness of breath, diffuse myalgias, headache, and lower
      extremity edema. He subsequently developed acute kidney injury and underwent
      kidney biopsy which showed MPGN and acute tubular injury. A tick-borne disease
      panel was positive for IgM and IgG to Ehrlichia chaffeensis. Serum testing
      revealed type 3 mixed cryoglobulinemia with no evidence of hepatitis C infection.
      The cryoprecipitate contained IgM and IgG antibodies to E. chaffeensis.
      Cryoglobulinemia is frequently associated with infections, particularly hepatitis
      C; however, our case is the first to describe ehrlichiosis associated with
      cryoglobulinemia and secondary MPGN.

PMID- 28509196
TI  - Acquired Fanconi syndrome due to long-term adefovir administration in a patient
      with IgG-kappa monoclonal gammopathy and kappa Bence-Jones protein.
AB  - A 77-year-old man was admitted to our hospital for a right femoral neck fracture.
      He had been prescribed lamivudine for chronic hepatitis B infection for 11 years,
      and adefovir was added 5 years ago. After hospitalization, a right femoral head
      prosthesis was performed successfully, but an unknown hypokalemia was revealed.
      Hypophosphatemia, hypouricemia, glucosuria, and panaminoaciduria were also
      revealed, and multiple microfractures were detected by bone scintigraphy. We
      diagnosed him as 'osteomalacia associated with Fanconi syndrome,' which was
      likely due to the adefovir. Moreover, a monoclonal IgG-kappa and a kappa Bence
      Jones protein were detected in his serum and urine, respectively. We switched
      from adefovir plus lamivudine to entecavir and started calcitriol. His excessive
      urinary beta2-microglobulin excretion and glucosuria had decreased dramatically
      at 10 weeks after the modification of drugs; those of the phosphate, uric acid
      and total protein, however, continued. Renal biopsy specimens obtained at 10
      weeks after discontinuation of adefovir revealed focal tubular atrophic changes
      with/without inflammatory cells, which were predominantly observed next to
      glomeruli. Kappa-dominant staining was not observed in either glomeruli or
      tubules with immunostaining by the enzyme-labeled antibody method. Electron
      microscopy revealed neither crystalline structures in the cytoplasm of proximal
      tubules nor electron-dense deposits. Because of the remarkable proportional
      reduction of other urinary protein fractions, urinary M-peak appeared 26 weeks
      after discontinuation of adefovir, but the net amounts of the fraction decreased
      gradually.

PMID- 28509197
TI  - Adefovir-induced Fanconi syndrome: diagnostic pearls and perils of late or missed
      diagnosis.
AB  - Low-dose adefovir therapy has been increasingly recognised as a cause of Fanconi
      syndrome. Being relatively novel, early diagnosis is both fraught with difficulty
      and yet of paramount importance given its far-reaching consequences, many of
      which are amenable to treatment. We discuss a patient who presented with
      hypokalemia and other electrolyte abnormalities suggestive of Fanconi syndrome
      whilst on adefovir for hepatitis B. A trans-tubular potassium gradient (TTKG =
      9.4) and urinary fractional phosphate excretion (39.4 %) consistent with renal
      potassium and phosphate wasting together with euglycemic glycosuria,
      aminoaciduria and hypophosphatemic osteomalacia supported the diagnosis of
      adefovir-induced Fanconi syndrome. With the cessation of the culprit drug, the
      patient has achieved partial recovery after 9 months. A high index of suspicion
      coupled with regular symptom surveillance and electrolyte monitoring is
      recommended in the course of adefovir therapy.

PMID- 28509198
TI  - Localized cystic disease of the kidney: case report and review of the literature.
AB  - Localized cystic disease of the kidney (LCDK) is a benign and non-progressive
      renal anomaly that may initially be confused with autosomal dominant polycystic
      kidney disease (as in the index case) or cystic neoplasms. It is best diagnosed
      with contrast-enhanced CT scan demonstrating the characteristic features of an
      unencapsulated mass of smooth-walled cysts with enhancing renal parenchyma
      between them. It is most often an incidental finding, but may present with flank
      pain or haematuria. Hypertension and renal impairment are uncommonly associated
      with LCDK. A complete physical examination and comprehensive family history are
      important to exclude other acquired or inherited causes of cystic kidney disease
      and to avoid unnecessary diagnostic procedures or nephrectomy. We describe a case
      manifesting many of the typical features of the condition and review previously
      published cases to describe the natural history and presentation of this rare
      entity.

PMID- 28509199
TI  - Graft versus host disease-dependent renal dysfunction after hematopoietic stem
      cell transplantation.
AB  - Nephropathy is an important complication in hematopoietic stem cell
      transplantation (HSCT) wherein multifactorial causes, i.e., radiation, drug
      toxicity, graft versus host disease (GVHD), are thought to contribute renal
      dysfunction. Here, we report a 10-year-old boy with high-risk acute myelocytic
      leukemia and severe but partially reversible renal dysfunction. The patient
      initially received umbilical cord blood transplantation (UCBT) with CY 120 mg/kg
      and kidney unshielded 12 Gy of total body irradiation. After the leukemic
      relapse, he received allogenic bone marrow transplantation (BMT) 270 days after
      the first transplantation. Two months later, his renal function started to
      deteriorate and urinary protein increased gradually to 1 g/day. Four months after
      BMT, by the symptoms of severe GVHD, the dose of tacrolimus, utilized to avoid
      GVHD, was increased although his serum Cre level elevated to 2.97 mg/dL. Serum
      Cre level improved to 2.0 mg/dL paralleled with GVHD improvement. Renal
      histological findings showed severe interstitial edema, features of thrombotic
      microangiopathy (TMA), and C4d deposition along the glomerular capillaries and
      peritubular capillaries. We suggested that control of GVHD had benefitted to
      ameliorate renal function of the patient. Treatment for GVHD improved renal
      dysfunction and TMA of our patients. Moreover, renal biopsy was powerful to
      elucidate the exact origin of renal dysfunction after HSCT.

PMID- 28509200
TI  - Staphylococcal empyema secondary to IgA nephropathy.
AB  - A 27-year-old male patient, applied to the emergency unit with complaints of high
      fever, nausea, vomiting, and hematuria. In his physical examination, fever was 38
      degrees C with normal findings in all other systems. The laboratory values were
      as follows: urea 58 mg/dL, creatinine 2.4 mg/dL, white blood cell count 15.9K/MUL
      (PNL: 79 %). In his urine analysis; +1 proteinuria and +3 hematuria were
      detected. Kidney biopsy was performed. Kidney biopsy interpreted in favor of IgA
      nephropathy. As the patient had tonic-clonic seizures, cranial CT examination was
      performed. In the cranial CT, there was a subdural effusion in the anterolateral
      area of the right cerebral hemisphere with the left shift in the midline
      secondary to the effusion. Empyema fluid, which was drained postoperatively, was
      cultured. In the direct examination of the empyema fluid, Gram positive cocci and
      abundant amount of PNLs were observed. There was no growth in the culture.
      Although the most commonly encountered agents for post-infectious
      glomerulonephritis are streptococcus infections, it has been reported that
      glomerulonephritis attacks may be rarely observed due to staphylococcus
      infections. Proliferative glomerulonephritis cases are rarely encountered
      conditions characterized by mesangial IgA accumulations secondary to
      staphylococcus infections.

PMID- 28509201
TI  - Diuretics-assisted treatment of chronic laxative abuse.
AB  - Hypopotassemia with acid-base imbalance caused by laxative abuse is one of the
      disorders that nephrologists can be consulted for. Although laxatives are not
      supposed to form psychological dependence in themselves and their abuse should be
      cured theoretically by just finishing the overdose, the patients often resist
      treatment due to unpleasant symptoms such as edema and worsening constipation.
      Thus, chronic laxative abuse is often regarded as a drug addiction. We report a
      successfully treated case of chronic laxative abuse, where drastic reduction of
      laxatives was achieved by applying diuretics. After drastic reduction of
      laxatives, diuretics were added until they eased edema and bloating so that the
      patient could feel them to be tolerable, paying attention to lab data such as
      potassium and renal function. The diuretics, which substituted for laxatives in
      fluid control, could be tapered off over 3 months without any withdrawal symptoms
      or a need of additional laxatives. Our experience of simple but successful
      treatment of chronic laxative abuse emphasizes importance of physical management
      and suggests that there are cases where the two different kinds of drugs,
      laxatives and diuretics, can practically be regarded as swappable in the
      treatment of laxative abuse. This presentation should contribute to accumulation
      of knowledge in how to treat chronic laxative abuse where no standardized method
      is established yet.

PMID- 28509202
TI  - Isolated complex renal cyst mimicking kidney mass.
AB  - Hydatidosis is an endemic parasitic disease in Mediterranean region, Middle east,
      Australia, parts of Africa, Latin America and Turkey. The cysts are mostly
      evident in the liver or lungs, while urinary tract involvement is uncommon,
      comprising only 2-4 % of all cases. Isolated renal involvement is extremely rare.
      Its diagnosis may be difficult because of nonspecific complaints and absence of
      pathognomonic laboratory findings except from hydatiduria. Although radiological
      studies have a more important role in the diagnosis, they cannot always show a
      specific sign or lesion for hydatid disease. Herein we present a rare case with
      isolated renal hydatid cyst mimicking a renal mass treated with right radical
      nephrectomy. Isolated renal cyst hydatid should be considered in differential
      diagnosis of both cystic and solid renal masses.

PMID- 28509204
TI  - Erratum to: Diuretics-assisted treatment of chronic laxative abuse.

PMID- 28509203
TI  - Chronic renal failure due to amyloid nephropathy caused by chronic infection
      after total hip replacement.
AB  - A 75-year-old woman was admitted to our hospital because of proteinuria, pitting
      edema on the foot, and renal impairment. She had undergone total hip replacement
      (THR) for femoral neck fracture at the age of 66. Nine years later, she met with
      an accident during farming and was treated at an emergency hospital for severe
      general trauma. On the basis of systemic symptoms, she was diagnosed with
      nephrotic syndrome. Renal biopsy by Congo-red staining and electron microscopy
      revealed amyloid deposition on glomeruli, interstitium, and interlobar arteries.
      The amyloid was immunohistochemically identified as AA amyloidosis. The patient
      eventually required maintenance hemodialysis because of impaired renal function.
      AA amyloidosis is an unusual complication of intractable inflammation. Chronic
      infection with abscess occurred around the artificial hip joint following THR and
      possibly induced secondary amyloidosis. THR is a common and necessary procedure
      adopted for femoral neck fracture. Orthopedic surgeons should, however, carefully
      monitor the occurrence of chronic infection after THR because such an infection
      could lead to renal dysfunction and/or failure via AA amyloidosis in rare cases.

PMID- 28509205
TI  - An 11-year-old girl with antineutrophil cytoplasmic antibody-associated
      glomerulonephritis identified by a school urinary screening program.
AB  - Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis (GN) in
      childhood is rare and has a poor prognosis. We report an 11-year-old girl with
      renal-limited antineutrophil cytoplasmic autoantibody-associated vasculitis.
      Proteinuria and hematuria were first detected by a school urinary screening (SUS)
      program. Histopathological examination revealed pauci-immune necrotizing GN. She
      did not display purpura or peripheral neuropathy. She was diagnosed with
      antineutrophil cytoplasmic autoantibody-associated GN based on proteinuria, high
      serum titers of antineutrophil cytoplasmic autoantibodies (ANCAs), and pauci
      immune necrotizing GN. The patient was treated with combination therapy,
      consisting of methylprednisolone and urokinase pulse, prednisolone, mizoribine
      (MZB), warfarin, and dilazep hydrochloride. At 2 months after treatment, urinary
      protein excretion was decreased and the hematuria had disappeared, while the
      serum titer of ANCAs was also decreased. The dose of prednisolone was tapered,
      and proteinuria and hematuria later disappeared at 9 months after treatment. In
      conclusion, we reported an 11-year-old girl with renal-limited antineutrophil
      cytoplasmic autoantibody-associated vasculitis early identified by a SUS program
      and treated with multi-drug combination therapy including MZB. On the basis of
      our results, we believe that a SUS programs may be effective for the early
      identification and treatment of children with renal-limited antineutrophil
      cytoplasmic autoantibody-associated vasculitis.

PMID- 28509206
TI  - Peritoneopericardial communication after aortic valve replacement in a peritoneal
      dialysis patient.
AB  - A 73-year-old male undergoing peritoneal dialysis (PD) for end-stage renal
      disease due to diabetic nephropathy was diagnosed with aortic stenosis and was
      admitted to our hospital in September, 2009. The patient underwent replacement of
      the ascending aorta with an artificial blood vessel plus aortic valve replacement
      without any notable complications. PD was restarted 3 days after the surgery and
      large amounts of light red fluid from the drain placed in the pericardium were
      observed just after resumption of PD solution. The patient was diagnosed with
      peritoneopericardial communication. PD was discontinued and hemodialysis was
      performed only with intermittent lavage of the peritoneal cavity. The amount of
      drainage was spontaneously decreased, and on the 17th day after surgery, PD was
      resumed. The patient is undergoing PD without recurrence of peritoneopericardial
      communication, 59 months after the onset of symptoms. Peritoneopericardial
      communication in a patient with PD developing after open-heart surgery is rare
      because such a case has been documented in only one case report. However, since
      massive pericardial effusion may cause severe cardiac problems, we consider that
      the communication between the peritoneal cavity and the pericardium needs to be
      checked for in patients with PD after cardiac surgery.

PMID- 28509207
TI  - Improvement in karyomegalic interstitial nephritis three years after ifosfamide
      and cisplatin therapy by corticosteroid.
AB  - Long-term nephrotoxicity of ifosfamide is occasionally progressive, and, in such
      case, there has been no specific treatment to prevent progression. It has been
      reported that the presence of karyomegalic interstitial nephritis, which is rare
      type of interstitial nephritis, may be related to ifosfamide-induced nephropathy
      with poor prognosis and resistant to the immunosuppressive therapy. A 15-year-old
      boy presented with progressive nephrotoxicity 3 years after systemic chemotherapy
      with ifosfamide and cisplatin for the treatment of osteosarcoma. Renal biopsy
      revealed the severe tubulointerstitial nephritis with tubular atrophy and focal
      global and segmental glomerular sclerosis. It also showed tubular epithelial
      cells with variably sized nuclei, some of which were massively enlarged, abnormal
      hyperchromatic, irregular shaped, and bizarre-appearing. These morphological
      changes were suggestive of the histology of karyomegalic interstitial nephritis.
      Corticosteroid retarded the progression of nephrotoxicity. The present case is
      the first report, suggesting that corticosteroid was effective against the late
      onset renal toxicity by ifosfamide therapy. Our case also suggests that
      karyomegalic interstitial nephritis may be the result of long-term nephrotoxicity
      of ifosfamide. Since concurrent treatment with cisplatin is one of the risk
      factors for ifosfamide nephrotoxicity, there is a possibility that cisplatin may
      have a synergetic effect with ifosfamide for producing karyomegalic interstitial
      nephritis.

PMID- 28509208
TI  - Rapidly developed diffuse myocardial calcification 13 days after septic shock in
      a hemodialysis patient.

PMID- 28509210
TI  - List of referees.

PMID- 28509209
TI  - Tocilizumab-induced remission of nephrotic syndrome accompanied by secondary
      amyloidosis and glomerulonephritis in a patient with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune-mediated systemic disorder that
      primarily affects the musculoskeletal system. Patients with RA often present with
      kidney diseases, such as nephrotic syndrome. Causes of nephrotic syndrome include
      membranous nephropathy, IgA nephropathy and secondary amyloidosis. Recently,
      biological agents, including anti-tumor necrosis factor alpha and anti
      interleukin 6 (IL-6) receptor antibodies, have been used for the treatment of RA.
      Anti-IL-6 receptor antibody therapy is believed to ameliorate RA-related kidney
      diseases, as IL-6 plays a central role in the pathogenesis of RA. We, herein,
      present the case of a patient with RA and related nephrotic syndrome whose
      proteinuria completely disappeared 1 month after tocilizumab treatment. A light
      microscopic examination of the pretreatment kidney biopsy specimen showed active
      glomerulonephritis with fibrocellular crescents and the deposition of amorphous
      substances stained weakly with hematoxylin-eosin and strongly with the Dylon
      method. Electron microscopy revealed the accumulation of microtubules ranging
      from 10 to 20 MUm in width, primarily in the mesangial lesion. Amyloid A (AA)
      protein was positively stained in the mesangial area and vascular wall on
      immunohistochemistry. The final histologic diagnosis was RA-related
      glomerulonephritis and secondary AA amyloidosis. This case indicates that
      biological treatment targeting IL-6 is a promising therapeutic option for the
      treatment of kidney diseases associated with RA.

PMID- 28509211
TI  - A case report of the anti-glomerular basement membrane glomerulonephritis with
      mesangial IgA deposition.
AB  - A 46-year-old Japanese male with a past medical history of microscopic hematuria
      presented with nausea, vomiting, and abdominal pain for which he had been
      diagnosed with rapidly progressive glomerulonephritis with a peak serum
      creatinine of 6.6 mg/dL and anti-glomerular basement membrane antibody of 214 EU.
      Light microscopy showed cellular crescent formation, and immunofluorescence
      illustrated both linear staining of IgG along the glomerular basement membrane
      and granular staining of IgA and C3 in the mesangial area; however, the PAS
      staining of mesangial expansions and mesangial proliferations were not observed.
      Clinical and histological findings suggested anti-glomerular basement membrane
      glomerulonephritis with mesangial IgA deposition, suggesting IgA nephropathy, a
      rare condition.

PMID- 28509212
TI  - Central diabetes insipidus and adipsia due to astrocytoma: diagnosis and
      management.
AB  - Adipsia and/or diabetes insipidus is rarely a direct complication of astrocytoma.
      We report a young man with recurrence of anaplastic astrocytoma who presented as
      severe hypernatremia. This case highlights key diagnostic and therapeutic
      challenges: (1) the interpretation of the response to exogenous vasopressin in a
      patient with steroid-induced hyperglycemia and (2) the potential risk of brain
      edema and herniation if excess water is prescribed along with vasopressin
      supplementation. The patient was successfully managed with prescribed fluid
      replacement, daily weights, and regular electrolyte monitoring but no exogenous
      vasopressin for 8 months until he succumbed to his tumor.

PMID- 28509213
TI  - A case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
      associated with lupus erythematosus in the central nervous system.
AB  - We report on a case of the syndrome of inappropriate secretion of antidiuretic
      hormone (SIADH) associated with lupus erythematosus in the central nervous system
      (CNS). A 73-year-old woman with essential hypertension suddenly demonstrated
      consciousness disturbance. Upon her admission, laboratory data showed significant
      hyponatremia (114 mEq/L) and a lack of body fluid loss. Diminished free water
      excretion (urine osmolality 684 mOsm/kg) and normal urine Na excretion (FENa 1.70
      %) were consistent with the diagnosis of SIADH, which was confirmed by an
      inappropriately high concentration of plasma antidiuretic hormone (ADH) (15.3
      pg/mL at 256 mOsm/kg of plasma osmolality). The hyponatremia was corrected by a
      combination of oral water intake restriction and saline infusion with furosemide
      administration until the 20th hospital day. Simultaneously, the presence of
      exudative pleural effusion in both chest cavities, suggesting the existence of
      pleuritis, and high titer of anti-nuclear antibody (ANA, 5120*) and anti-double
      strand DNA antibody (6500 IU/mL), indicated the subclinical development of
      systemic lupus erythematosus (SLE), although the diagnostic criteria were not
      satisfied at that time. On the 34th hospital day, the sudden onset of unknown
      consciousness disturbance confirmed the diagnosis of SLE as CNS lupus. In
      previous case reports on SLE and/or SIADH, a few cases in which SLE and SIADH
      developed concomitantly regularly showed high immunological activities, as in our
      case. Some common pathophysiological bases might be involved in the concomitant
      appearance of those disorders.

PMID- 28509214
TI  - Severe metabolic alkalosis, hypokalemia, and respiratory acidosis induced by the
      Chinese herbal medicine yokukansan in an elderly patient with muscle weakness and
      drowsiness.
AB  - Yokukansan is a Chinese herbal medicine containing licorice that has been shown
      to alleviate the behavioral and psychological symptoms of Alzheimer's disease,
      with few adverse effects. Increasing numbers of patients with Alzheimer's disease
      in Japan are now being treated with this drug. However, yokukansan should be used
      with caution because of its potential to induce pseudoaldosteronism through the
      inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes
      cortisol into cortisone. We present the case of an 88-year-old woman with a
      history of Alzheimer's disease who was transferred to our emergency department
      because of drowsiness, anorexia, and muscle weakness. Her blood pressure was
      168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic
      alkalosis (pH 7.54; HCO 3- , 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140
      mmol/l), and respiratory disorders (pCO2, 60.5 mmHg; pO2, 63.8 mmHg). Plasma
      renin activity and aldosterone concentration were suppressed, and urinary
      potassium excretion was 22 mmol/l (calculated transtubular potassium gradient
      12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular
      premature contractions. Echocardiography denied volume depletion. Medical
      interview disclosed that she had been treated with a Chinese herbal medicine
      (yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and
      respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and
      respiratory acidosis all subsided shortly after the discontinuation of yokukansan
      and initiation of intravenous potassium replacement. This case highlights the
      need for nephrologists to consider the possible involvement of Chinese herbal
      medicines, including yokukansan, when they encounter hypokalemia in elderly
      patients.

PMID- 28509215
TI  - De novo acute hepatitis B in myeloperoxidase-specific anti-neutrophil cytoplasmic
      autoantibody-related microscopic polyangiitis treated with corticosteroids.
AB  - An 82-year-old female was referred to our hospital because of low-grade fever,
      anemia, and rapidly progressive nephritic syndrome. Her laboratory data showed
      mild proteinuria, mild renal failure, and the presence of myeloperoxidase
      specific anti-neutrophil cytoplasmic autoantibody. A skin biopsy specimen taken
      from the erythematous purpura revealed neutrophilic infiltration around the blood
      vessels with fibrinoid changes in the vessel walls. A renal biopsy specimen
      revealed segmental necrotizing glomerulonephritis with fibro-cellular crescent
      formation without deposits of immunoglobulin or complement components, indicating
      microscopic polyangiitis. The use of corticosteroid treatment, including
      intravenous methylprednisolone, improved renal failure. After 4 years with low
      dose maintenance corticosteroid therapy, she developed de novo acute hepatitis B,
      and entecavir was remarkably effective, showing a rapid recovery from liver
      dysfunction with jaundice. To prevent hepatitis B virus (HBV) reactivation and de
      novo acute hepatitis B induced by immunosuppressive or cytotoxic therapy,
      including corticosteroids alone, the measurement of HBV-related serological
      markers needs to be performed prior to the initiation of such therapy, even in
      renal diseases.

PMID- 28509216
TI  - A distinct lymphocyte distribution in relapse after rituximab for steroid
      dependent nephrotic syndrome.
AB  - Rituximab (RTX) is a new steroid-sparing therapy for childhood steroid-dependent
      nephrotic syndrome (NS). However, relapses frequently occur immediately after
      CD19 recovery. We report the cases of two steroid-dependent NS patients treated
      with RTX followed by mizoribine (MZB). One patient relapsed, and the other
      developed proteinuria after CD19 recovery until the MZB was replaced by
      mycophenolate mofetil. These patients exhibited different lymphocyte phenotypes,
      with the CD4+/CD8+ profile favoring CD8+ T lymphocytes, while CD3+ HLA-DR
      expressing activated T lymphocyte expansion occurred in the relapsed patient.
      Based on these findings, we suggest that T cell activation may influence outcome
      and that phenotypic analysis in addition to B cell monitoring may facilitate the
      detection of NS relapse.

PMID- 28509217
TI  - Scleroderma renal crisis in a newly diagnosed mixed connective tissue disease
      resulting in dialysis-dependent chronic kidney disease despite angiotensin
      converting enzyme inhibition.
AB  - Mixed connective tissue disease (MCTD) is a rheumatic disease with a combination
      of multiple connective tissue disorders, which includes dermatomyositis or
      polymyositis, systemic sclerosis, systemic lupus erythematosus, rheumatoid
      arthritis and Sjogren's syndrome. It affects various organs of the body, which
      includes the lungs, heart, kidneys, joints, muscles and the haematological
      system. Here, we report a case of MCTD consisting of scleroderma, Sjogren's
      syndrome and polymyositis complicated by scleroderma renal crisis (SRC) but with
      negative anti-nuclear antibody (ANA), anti-Scl 70 and anti-centromere antibodies.
      The patient was started on captopril for the treatment of SRC but developed
      chronic kidney disease despite adequate blood pressure control with angiotensin
      converting enzyme inhibitor (ACEi).

PMID- 28509218
TI  - Acute kidney injury due to acyclovir.
AB  - Acyclovir is an antiviral agent widely used in herpetic infections in children.
      Although acyclovir is generally well tolerated, severe nephrotoxicity has been
      reported in some cases. In this report, we present a 16-year-old girl who
      developed acute renal failure due to acyclovir treatment and who needed
      repetitive hemodialysis. Renal biopsy was performed in order to confirm the
      diagnosis. A diagnosis of drug-related acute tubulointerstitial nephritis with
      focal tubular necrosis was made.

PMID- 28509219
TI  - Atypical hemolytic uremic syndrome with MCP mutations preceded by respiratory
      infection.
AB  - A 14-year-old boy was referred to our hospital with general fatigue and sore
      throat. A chest X-ray and computed tomography revealed diffuse bilateral
      bronchitis. A laboratory examination showed anemia, thrombocytopenia, and renal
      insufficiency. He had a past medical history of hemolytic uremic syndrome (HUS)
      without diarrhea at the age of 3; moreover, his elder brother suffered from HUS
      at the age of 12. These findings indicated that the patient had a familial
      relapsing form of HUS (atypical HUS). Therefore, he was immediately treated with
      plasma exchange (PE), as suggested by guidelines, obtaining complete remission.
      Fifteen months later, he suffered another relapse of atypical HUS preceded by
      respiratory infection and was cured again with PE. His ADAMTS-13 activity was
      normal and its inhibitory antibody was undetectable. Two different mutations were
      found in the gene encoding membrane cofactor protein (MCP). Respiratory
      infections preceded all three episodes of HUS, but we could not detect the
      pathogenic agent. Although the long-term outcomes of patients with atypical HUS
      who have mutations in the MCP gene appear favorable, recurrences are nevertheless
      frequent. Few reports have described Japanese patients with atypical HUS and
      complement regulatory abnormalities. This is the first report of a Japanese
      patient with atypical HUS and mutations in the MCP gene.

PMID- 28509220
TI  - A case presenting with the possible relationship between myeloperoxidase
      antineutrophil cytoplasmic antibody-associated glomerulonephritis and membranous
      changes of the glomerular basement membrane.
AB  - A 72-year-old woman exhibited elevated serum myeloperoxidase-antineutrophil
      cytoplasmic antibody (MPO-ANCA) levels since 2006. Her serum creatinine (sCr)
      levels increased from 0.5 to 1.62 mg/dl in a stepwise pattern with proteinuria
      and hematuria up to January 2011. Renal biopsy indicated global sclerosis (14 %),
      fibrocellular crescents (28 %), and Swiss cheese-like appearance of the
      glomerular basement membrane (GBM) on light microscopy. IgG4 staining was
      negative. Immunofluorescent examination indicated granular staining with IgG and
      C3 along the GBM. MPO-ANCA-associated glomerulonephritis with membranous
      nephropathy (MN) was diagnosed. As chronic changes were relatively evident in the
      renal biopsy specimen without acute augmentation of renal function,
      immunosuppressive therapy was not administered. Thereafter, rapidly progressive
      renal dysfunction occurred (sCr, 3.67 mg/dl in May 2011) with proteinuria (~2
      g/day), hematuria, and elevated serum MPO-ANCA levels. Therefore, a second renal
      biopsy was performed in May 2011, indicating global sclerosis (42 %) and cellular
      crescents (35 %) on light microscopy. Electron microscopy indicated electron
      dense deposits in the GBM and mesangial lesions. Steroid therapy was subsequently
      initiated, and the patient's renal function partially improved. MPO-ANCA levels
      decreased to within normal limits and hematuria disappeared. MPO-ANCA-associated
      glomerulonephritis with MN is a rare dual glomerulopathy. However, complication
      should be considered when urinary protein appears in large amounts. Secondary MN
      was suspected due to the lack of IgG4 staining and distribution of electron-dense
      deposits to the mesangial lesion. Renal dysfunction occurring in a stepwise
      pattern may be attributed to intermittent augmentation in MPO-ANCA-associated
      glomerulonephritis.

PMID- 28509221
TI  - Development of systemic lupus erythematosus in an elderly male hemodialysis
      patient with pleuritis.
AB  - This report describes a 70-year-old man who developed systemic lupus
      erythematosus (SLE) during treatment with maintenance hemodialysis. At initiation
      of maintenance dialysis, the etiology of end-stage renal disease (ESRD) was
      diabetic nephropathy and no clinical symptom or laboratory data suggested SLE.
      Fever, pleural effusion that did not respond to ultrafiltration, and
      immunological findings such as low complement and elevated anti-double-strand DNA
      antibody level appeared 4 years after maintenance dialysis initiation.
      Immunosuppressive therapy with corticosteroids improved these abnormalities
      remarkably. This case underscores the necessity of considering SLE in the
      differential diagnosis of pleural effusion with male ESRD patients, even if
      another etiology of ESRD exists.

PMID- 28509222
TI  - Fabry's disease discovered with chance urinary mulberry cells: a case report.
AB  - Fabry's disease (FD) is a rare X-linked lysosomal storage disorder. Novel enzyme
      replacement therapy (ERT) at an early stage can slow the progression of
      cardiovascular and renal dysfunction. Urinary mulberry cells are occasionally
      found in renal FD. We report a case of variant FD in which detection of urinary
      mulberry cells led to an early diagnosis. A 36-year-old Japanese man was referred
      to our hospital because mulberry cells had been detected during urinalysis.
      Proteinuria and renal dysfunction were not observed. His plasma alpha
      galactosidase activity was very low. Renal biopsy revealed typical foamy changes
      in the glomerular podocytes and tubular epithelial cells that are found in renal
      FD. Based on the detection of urinary mulberry cells, we successfully started ERT
      before the patient's renal function deteriorated. Clinical nephrologists and
      laboratory technicians should recognize the importance of screening for mulberry
      cells during urinalysis as this is a simple, inexpensive, and non-invasive method
      for diagnosing FD.

PMID- 28509223
TI  - Lupus nephritis class I accompanied by tubulointerstitial nephritis with marked T
      lymphocyte infiltration in an HTLV-1 positive patient.
AB  - We herein describe the case of a 40-year-old Japanese male who was admitted to
      our hospital because of a continuous remittent fever lasting 1 month. He
      fulfilled the items of the classification criteria for the diagnosis of systemic
      lupus erythematosus (SLE). The administration of 20 mg per day of oral
      prednisolone completely diminished his clinical symptoms. However, his renal
      biopsy performed 1 day after the admission showed marked pathognomonic
      characteristics. Not only did his glomeruli show class I lupus nephritis with
      mesangial depositions of IgG, IgA, C3, and C1q, but also tubulointerstitial
      nephritis with marked T-lymphocyte infiltration. These infiltrated T cells partly
      had nuclear atypia. The patient was positive for human T cell leukemia virus type
      1 (HTLV-1) antibodies. Furthermore, clonal rearrangements of T cell receptor
      gamma chain gene was detected in the DNA extracted from his kidney sections by
      the polymerase chain reaction (PCR) method. A second renal biopsy 6 months after
      the prednisolone treatment showed that the infiltrating T lymphocytes had
      markedly diminished. This is the first case report of lupus nephritis class I
      with tubulointerstitial nephritis, which might include oncogenic T lymphocytes,
      in an HTLV-1 positive patient.

PMID- 28509224
TI  - Successful kidney transplantation for a dialysis patient with anthracycline
      induced cardiomyopathy: a case report.

PMID- 28509225
TI  - A case of membranoproliferative glomerulonephritis developed over twenty years
      with three different findings of renal pathology.
AB  - A 31-year-old woman with proteinuria, hypocomplementemia, rheumatoid factor, and
      high serum polyclonal IgM concentration was admitted to our hospital for renal
      biopsy. She had a past history of two renal biopsies. When she was 12 years old,
      she developed proteinuria, microscopic hematuria, and hypocomplementemia. She was
      diagnosed as having 'IgM nephropathy' based on minor glomerular abnormalities as
      determined by light microscopy and IgM and C3 deposition in the mesangial region
      by immunofluorescence microscopy at the first biopsy. Despite corticosteroid
      treatment, her proteinuria did not improve and she discontinued regular
      outpatient checkups. When she was 29 years old and pregnant, she developed
      preeclampsia and, after delivery, a second renal biopsy was implemented. She was
      diagnosed as having progressed 'IgM nephropathy' with endotheliosis induced by
      preeclampsia. She was treated with angiotensin II receptor blocker and her
      proteinuria diminished; however, 1 year after the delivery, she developed
      proteinuria again, along with microscopic hematuria and hypocomplementemia. A
      third renal biopsy was conducted at 31 years of age and she was diagnosed as
      having membranoproliferative glomerulonephritis (MPGN) type I on the basis of
      diffuse mesangial proliferation, endocapillary hypercellularity with double
      contour of the capillary wall, and lobular formation in glomeruli, as determined
      by light microscopy. Immunofluorescence staining demonstrated deposits of C3, C4,
      C1q, and IgM in the mesangial region and capillary wall. She underwent
      corticosteroid therapy followed by normalization of urinalysis and serum
      complement level. Although she had initially been diagnosed with 'IgM
      nephropathy', she was finally diagnosed with secondary MPGN and was successfully
      treated by corticosteroid therapy.

PMID- 28509226
TI  - Cytomegalovirus and Aspergillus spp. coinfection in organ transplantation: a case
      report and review of the literature.
AB  - With the advent of potent immunosuppressive options, acute rejection episodes
      have decreased at the expense of increased incidence of opportunistic infections
      in solid organ recipients. In the absence of any preventive therapy, 30-75 % of
      transplant recipients develop cytomegalovirus (CMV) infection. Candida spp. and
      Aspergillus spp. account for more than 80 % of invasive fungal infections in
      solid organ recipients. This co-occurrence of two commonly seen opportunistic
      infections may end up in fatality. Here, we present a case of concomitant
      Aspergillus spp. and CMV infection and discuss the relevant literature. A 54-year
      old male patient presented with fever, shortness of breath, and chest pain on the
      9th posttransplant week after renal transplantation. CMV-DNA by polymerase chain
      reaction (PCR) was 1,680,000 copies/ml, thus, valganciclovir dose was increased.
      There were inspiratory crackles at both lung bases, and chest computed tomography
      (CT) revealed multiple fungal balls throughout the right lung. Galactomannan
      antigen was positive, and voriconazole and other antimicrobials were subsequently
      added to the treatment. At the end of the therapy, on control CT, pneumonic
      consolidation had disappeared, sputum cultures didn't show Aspergillus spp., and
      CMV-DNA reduced to 700 copies/ml. The patient showed a favorable clinical
      response to combined treatment; fever, dyspnea, and pleuritic chest pain
      disappeared. Both CMV disease and aspergillosis may present as pulmonary disease;
      thus, the characterization of one may not preclude the search for the other and
      the timely initiation of treatment is of paramount importance for good outcomes.

PMID- 28509227
TI  - A case of secondary focal segmental glomerulosclerosis associated with malignant
      hypertension.
AB  - Focal segmental glomerulosclerosis (FSGS) is associated with various
      clinicopathological conditions, including hypertension. We report here a case of
      secondary FSGS associated with malignant hypertension. A 33-year-old man with a 1
      month history of visual impairment and headache visited the Department of
      Ophthalmology at our hospital and was found to have hypertensive retinopathy and
      severe hypertension (230/160 mmHg). He was referred to our department based on
      suspected renal dysfunction. His blood pressure on admission was 250/130 mmHg.
      Physical examination and laboratory tests revealed hypertensive cardiac
      dysfunction, focal brain edema, renal dysfunction (serum creatinine, Cr 7.07
      mg/dl, blood urea nitrogen, BUN 49.9 mg/dl), massive proteinuria (10.7 g/day),
      and thrombotic microangiopathy. Funduscopy showed exudate, hemorrhage, and
      papilledema. The cause of secondary hypertension could not be identified. He was
      treated for primary malignant hypertension, but required hemodialysis 3 days
      after admission due to anuria. Treatment with antihypertensive agents resulted in
      the gradual recovery of renal function, although heavy proteinuria continued with
      nephrotic syndrome. Renal biopsy performed 1 month after admission showed
      features of malignant nephrosclerosis with secondary FSGS. Hemodialysis was
      discontinued following further improvement in renal function and the most recent
      laboratory tests showed proteinuria 1.8 g/day and persistent renal dysfunction
      (BUN 36.5 mg/dl, Cr 3.14 mg/dl). Malignant hypertension may cause various
      injuries, including glomerular endothelial and epithelial cell injuries in
      glomerular hypertension and hyperfiltration, increase of the renin-angiotensin
      aldosterone system, and endothelial-epithelial interaction, resulting in the
      development of secondary FSGS and heavy proteinuria.

PMID- 28509228
TI  - Renal transplantations from parents to siblings with autosomal recessive Alport
      syndrome caused by a rearrangement in an intronic antisense Alu element in the
      COL4A3 gene led to different outcomes.
AB  - Two siblings with autosomal recessive Alport syndrome (ARAS) obtained renal
      transplants from their consanguineous parents. Their COL4A3 mRNA transcripts were
      disrupted by a 139 bp intronic sequence between exon 48 and 49, which was derived
      from an antisense Alu element in this intron. The new amino acid sequence from
      the cryptic exon was terminated by a stop codon at the 1511th codon, resulting in
      the loss of 76 % alpha3(IV)NC1. This is the first case report of kidney
      transplantations between ARAS-homozygous siblings and their heterozygous parents.
      The brother experienced acute rejection just after transplantation and post
      transplantation anti-glomerular basement membrane (GBM) nephritis, whereas the
      sister has experienced no problems to date. The anti-GBM nephritis could have
      resulted from the acute rejection. The COL4A3 gene heterozygous mutated parents,
      who are possibly at risk for thin basement membrane disease, have maintained
      their renal functions without urinary abnormalities after renal transplantation
      to date.

PMID- 28509229
TI  - Atypical sarcoidosis diagnosed by bone marrow biopsy during renal workup for
      possible multiple myeloma.
AB  - Sarcoidosis is a multi-organ disease of unknown etiology characterized by non
      caseating granulomas. Here we report the case of a 78-year-old white male with a
      past medical history of diabetes mellitus, hypertension, and chronic kidney
      disease stage III with a baseline serum creatinine of 2.5 mg/dl. The patient had
      a prior admission history for acute kidney injury (AKI) attributed to dehydration
      and medication-induced nephro-toxicities. He presented to the renal clinic for
      follow-up with acute worsening of chronic kidney failure with a serum creatinine
      level of 3.5 mg/dl. Examination revealed that he was anemic and mildly
      hypercalcemic with suppressed parathyroid hormone and had proteinuria of 1.3 g
      per day. The computed tomography scan of the abdomen revealed right renal pelvic
      non-obstructing calculi. Serum protein electrophoresis revealed gammopathy with
      two distinct monoclonal peaks consisting of immunoglobulin G (IgG) kappa and IgG
      lambda, respectively. The kappa/lambda ratio was within normal limits, and urine
      protein electrophoresis showed no evidence of a monoclonal peak or Bence Jones
      proteins. Further workup for multiple myeloma, including bone marrow (BM) biopsy,
      revealed polyclonal plasma cells and B cells with no clonality. No morphological
      and immune-phenotypic evidence of plasma cell dyscrasia was found, but BM biopsy
      did show numerous non-caseating granulomas consistent with sarcoidosis. Skin
      biopsy from non-scaly 6-mm skin colored papule also showed non-caseating
      granulomas. The patient had elevated angiotensin-converting enzyme levels (165
      ug/l) and an erythrocyte sedimentation rate of 27 mm/h. Kidney biopsy did not
      show granulomas. The hypercalcemia, proteinuria, and AKI responded well after 2
      weeks of 60 mg oral prednisone daily.

PMID- 28509230
TI  - Methylprednisolone pulse therapy and intravenous cyclophosphamide therapy
      combined with cocktail therapy in severe pediatric Henoch-Schonlein purpura
      nephritis patient.
AB  - Henoch-Schonlein purpura (HSP) is a common self-limited vasculitis in children.
      The long-term prognosis depends on renal involvement. In severe Henoch-Schonlein
      purpura nephritis (HSPN) patients, >50 % have crescent formation and nephrotic
      syndrome that are important predicted outcomes. Therefore, for such patients, an
      aggressive immunosuppressive therapy is needed to prevent the progression.
      However, there is no consensus for an appropriate therapeutic regimen for severe
      pediatric HSPN patients. In this paper, we have reported on a 6-year-old boy who
      presented with HSPN with nephrotic syndrome and severe histopathological
      abnormalities; he was diagnosed with International Study of Kidney Disease in
      Children (ISKDC) grade IVb. Despite treatment with methylprednisolone pulse
      therapy, followed by oral prednisolone and dipyridamole; the nephrotic syndrome
      persisted. Subsequently, intravenous cyclophosphamide therapy (IVCY) (500-1,000
      mg m-2 once a month for 7 months; total 6,000 mg m-2) was administered, followed
      by azathioprine and enarapril. Within 7 months of disease onset, complete
      remission was achieved. After 22 months of the initial renal biopsy, the second
      biopsy was performed to confirm treatment efficacy. Histopathological findings
      improved, and ISKDC grade IIIa was diagnosed. Even after 5 years of HSPN onset,
      complete remission and normal renal function is maintained. Although our evidence
      is restricted to single patient, we have shown that MPT and IVCY combined with
      cocktail therapy may be an effective treatment for severe pediatric HSPN.

PMID- 28509231
TI  - Two cases of eating disorder revealed by the breakout of acute kidney injury
      after angiotensin II receptor blocker administration.
AB  - Case 1: A 39-year-old woman with schizophrenia, obesity, hypertension and
      dyslipidemia was admitted to our hospital for deteriorating serum Cr level, from
      97.2 to 645.3 umol/l. She had been started on losartan 5 months earlier. After
      suspension of losartan and infusion of saline, her serum Cr level gradually
      recovered and she was discharged. Unfortunately, her physician restarted her on
      losartan, and 5 months after this discharge, her serum Cr level rose again to
      194.5 MUmol/l; again, serum Cr promptly recovered when losartan was discontinued.
      Self-induced vomiting after overeating, suggesting bulimia nervosa, was revealed
      via the detection of a remarkable reduction of chloride compared to sodium in her
      spot-urine sample. Case 2: A 39-year-old woman who had been diagnosed with
      bipolar disorder and diabetes mellitus was admitted to our hospital with
      suspected diabetic ketoacidosis. After improvement in her blood sugar level,
      olmesartan administration for hypertension was begun. Four days later, her serum
      Cr level had risen from 60.1 to 256.4 MUmol/l. After suspension of olmesartan and
      infusion of saline, her serum Cr level gradually fell to normal levels.
      Urinalysis revealed the dissociation of sodium and chloride. During her
      hospitalization, habitual self-induced vomiting was discovered. The measurement
      of urinary electrolytes may be useful for the detection of eating disorders with
      self-induced vomiting; in these patients, the administration of angiotensin II
      receptor blockers may induce acute kidney injury.

PMID- 28509232
TI  - A case of MPO- and PR3-ANCA-negative pauci-immune renal-limited small-vessel
      vasculitis associated with endometrial neuroendocrine small cell carcinoma.
AB  - A 69-year-old woman was admitted to our hospital for rapid increase in serum
      creatinine level with microscopic hematuria and nephrotic-range proteinuria.
      Three months prior to admission, she became aware of atypical genital bleeding,
      leading her gynecologist to suspect endometrial cancer. Light microscopy
      examination of renal biopsy revealed crescentic glomerulonephritis with
      peritubular capillaritis. Immunofluorescence microscopic examination did not
      detect any significant staining, and no electron-dense deposits were detected by
      electron microscopy. No autoantibodies, including anti-myeloperoxidase- or anti
      proteinase3-anti-neutrophil cytoplasmic antibodies were detected. The patient
      underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and
      was found to have endometrial neuroendocrine small cell carcinoma (NSCC), stage
      1B. In her clinical course, her serum creatinine level gradually improved without
      immunosuppression therapy. Endometrial NSCC is a rare endometrial malignancy.
      This is the first case report of vasculitis associated with NSCC originating from
      the uterus.

PMID- 28509233
TI  - Hyponatremia associated with demyelinating disease of the nervous system.
AB  - A 63-year-old man was diagnosed with periodontitis and underwent tooth
      extraction. Several days later, he suffered a high fever, ischuria, a change in
      personality, and disorientation. A urologist examined him and found severe
      hyponatremia (117 mEq/L), and he was then transferred to our hospital. On
      admission, physical findings revealed dysfunction of the bladder and bowel,
      altered mental status, and hypovolemia. Blood chemistry showed serum sodium of
      120 mEq/L, a serum urate of 1.4 mg/dL, urinary Na of 61 mEq/L, and fractional
      urate excretion of 16 %. Examination of the cerebrospinal fluid (CSF) showed
      monocytosis. Magnetic resonance imaging (MRI) of the brain and spinal cord showed
      multiple lesions characterized by hyperintensity on T2-weighted sequences,
      suggesting demyelinating disease. His sodium concentration normalized 3 days
      after volume replacement therapy, and his altered mental status along with the
      dysfunction of the bladder and bowel were promptly improved after the initiation
      of high-dose glucocorticoids. Additionally, the abnormal lesions on MRI markedly
      decreased. This clinical course led to the likely diagnosis of acute disseminated
      encephalomyelitis (ADEM). Hyponatremia in neurologically injured patients is
      usually attributed to the syndrome of inappropriate antidiuretic hormone (SIADH)
      or cerebral salt-wasting syndrome (CSWS). In the present patient, the uric acid
      level remained low and uric acid excretion remained elevated despite correction
      of the hyponatremia, which suggested CSWS. The differentiation of CSWS from SIADH
      is difficult but critically important due to the fact that the disorders are
      managed differently. Coexistence of ADEM and CSWS has rarely been reported.

PMID- 28509234
TI  - Combined membranous nephropathy and crescentic glomerulonephritis with concurrent
      anti-glomerular basement membrane antibody and myeloperoxidase-specific anti
      neutrophil cytoplasmic antibody.
AB  - We report a case of a 71-year-old man with rapidly progressive nephritic syndrome
      and dual positivity for anti-glomerular basement membrane antibody and
      myeloperoxidase-specific anti-neutrophil cytoplasmic antibody. Renal biopsy
      revealed crescentic, mainly cellular, glomerulonephritis with granulomatous
      lesions, and advanced membranous changes. Membranous nephropathy had apparently
      existed for an extended period before the development of crescentic
      glomerulonephritis. In some studies reporting the simultaneous occurrence of both
      diseases, membranous nephropathy might be followed by crescentic
      glomerulonephritis, presumably from a histological point of view. Although we
      cannot prove a causal relationship between the two diseases, we caution that
      precise observations, especially histological, are necessary in similar cases.

PMID- 28509236
TI  - Renal cell neoplasm of oncocytosis: a type of unclassified renal cell carcinoma.
AB  - A 69-year-old woman was referred to us because a cyst in the lower pole of the
      left kidney had been pointed out on screening ultrasound. Computed tomography
      (CT) demonstrated a mural nodule of the wall of the cyst with an enhancement
      effect, suggesting cystic renal cell carcinoma (cT1aN0M0). The patient underwent
      retroperitoneoscopic non-ischemic partial nephrectomy using a microwave tissue
      coagulator. A hematoxylin-eosin-stained specimen showed that the wall of the
      cystic tumor consisted of the proliferation of large cells with rich eosinophilic
      granules in the cytoplasm and round-shaped nuclei, which were the characteristics
      of oncocytoma. This was followed by immunohistochemical studies, because of
      findings of local cell invasion, mitosis, and necrosis, suggesting malignancy.
      The results were: CK7, strongly positive; PAX2, negative; colloidal iron stain,
      negative; c-kit, weakly positive; vimentin, positive; and RCC marker, negative.
      Thus, although the tumor showed characteristics of oncocytoma and/or chromophobe
      renal cell carcinoma (pT1a), it could not be classified according to the known
      categories: it should be designated as renal cell carcinoma (neoplasm) of
      oncocytosis, a novel category of unclassified renal cell carcinomas. The present
      case indicated the fact that renal cell carcinomas resembling oncocytoma
      certainly exist.

PMID- 28509235
TI  - Monitoring with serum SP-A, SP-D, and KL-6 in a patient with interstitial
      pneumonia complicated with ANCA-associated glomerulonephritis.
AB  - A 69-year-old woman was admitted to hospital, complaining of fatigue and dry
      cough. Her renal function deteriorated rapidly, and the laboratory findings
      showed elevated myeloperoxidase-specific anti-neutrophil cytoplasmic antibody
      (ANCA). Renal biopsy examination revealed crescentic glomerulonephritis (pauci
      immune type), and linear opacities and a honeycomb appearance in both lower lobes
      was evident on the chest computed tomography scan. The patient was diagnosed as
      having ANCA-associated glomerulonephritis complicated with mild interstitial
      pneumonia (IP). Treatment with methylprednisolone pulse therapy improved both her
      renal function and IP, but her lung lesions worsened during the course of
      tapering the prednisolone doses. After careful observation, her IP improved
      gradually without specific treatment. Worsening or improvement of her lung
      lesions was accompanied by changes in the serological markers of IP, namely,
      surfactant protein-A, surfactant protein-D, and KL-6. We found that monitoring
      these markers was helpful in diagnosing and managing IP in our patient with ANCA
      associated vasculitis.

PMID- 28509237
TI  - Superior mesenteric artery syndrome due to duodenal edema in a chronic renal
      failure patient: a case report.
AB  - A 74-year-old woman had been treated conservatively for type 2 diabetes mellitus
      (DM) and DM nephropathy since 2004. Her renal function gradually deteriorated,
      and she developed chronic renal failure (CRF) with a serum creatinine level
      between 2.5 and 3.0 mg/dl in 2010. She presented to our hospital with nausea and
      vomiting related to the progression of CRF in May 2011. An abdominal computed
      tomography (CT) scan showed distention of the upper digestive tract from the
      stomach to the third portion of the duodenum, ascites, and compression of the
      duodenum by the abdominal aortic artery and the overlying superior mesenteric
      artery (SMA), which was caused by edema along the gastrointestinal tract, in
      particular, at the duodenum. Therefore, she was diagnosed with SMA syndrome.
      Decompression of the distended upper digestive tract was achieved using a
      nasogastric tube, and hemodialysis was also initiated in order to adequately
      control her fluid balance disorder, which was thought to have induced the
      duodenal edema and ascites. After initiating these treatments, her condition
      gradually improved, and she fully recovered after approximately 2 months of
      treatment. Thus far, there has been no report of SMA syndrome caused by duodenal
      edema associated with the progression of CRF that was successfully treated by
      conservative treatment and the initiation of blood purification.

PMID- 28509238
TI  - Membranous nephropathy associated with type 1 autoimmune pancreatitis and
      dominant glomerular IgG4 deposit.
AB  - We report a case of membranous nephropathy associated with type 1 autoimmune
      pancreatitis. A 58-year-old man presented with anorexia. Work-up revealed a mass
      in the pancreatic head, which was subsequently resected. Pathological examination
      showed diffuse infiltration of immunoglobulin (Ig) G4-positive plasma cells,
      which was compatible with the diagnosis of type 1 autoimmune pancreatitis. Serum
      IgG4 was elevated. He developed nephrotic syndrome around the time of the
      surgery. Kidney biopsy confirmed the diagnosis of membranous nephropathy.
      Immunofluorescent staining showed predominant glomerular IgG4 deposit among IgG
      subclasses. Tubulointerstitial nephritis, which is usually a dominant feature of
      renal involvement in IgG4-related disease, was not observed. The patient was
      treated with prednisolone and several immunosuppressants. During the course, the
      degree of proteinuria was associated with the serum IgG4 level. Serum antibody
      against phospholipase A2 receptor was negative. These findings together with IgG4
      dominant glomerular deposit suggest that IgG4 may play a unique role in the
      pathogenesis of secondary membranous nephropathy caused by IgG4-related diseases.

PMID- 28509240
TI  - Cytokine dynamics in a 14-year-old girl with tubulointerstitial nephritis and
      uveitis syndrome.
AB  - Tubulointerstitial nephritis and uveitis (TINU) syndrome, which was first
      described in 1975, has been reported in more than 130 patients, mostly in
      adolescent or young women. Although data concerning the etiologic background of
      this inflammatory disease are limited, several humoral factors, including
      cytokines, have been reported in association with the disease. Here, we report a
      case of TINU in a 14-year-old girl, whose renal and ophthalmological improvement
      was associated with the decrease of serum levels of tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-8 (IL-8). This
      suggests the presence of T-cell-mediated immunity in this unique syndrome.

PMID- 28509239
TI  - An autopsy case that manifested no convincing histological changes of severe
      renal failure after hematopoietic stem cell transplantation.
AB  - A 48-year-old Japanese woman, who had been diagnosed with smoldering adult T-cell
      leukemia, was admitted to our hospital for hematopoietic stem cell
      transplantation (HSCT) because of an acute exacerbation of her disease. After
      myeloablative conditioning procedures, comprising cytarabine with
      cyclophosphamide and total body irradiation, the HLA-matched unrelated bone
      marrow stem cells were infused (day 0). Her serum creatinine concentration,
      having been 0.6 mg/dL at baseline, began to increase from day 1 and was 2.3 mg/L
      on day 7. Hemodialysis was required to treat fluid overload and worsening uremia
      on days 8 and 9. On day 10, she presented with refractory hypotension and died
      due to multi-organ failure on day 12. Renal pathology at autopsy showed no
      specific histological changes to which her clinically severe acute kidney injury
      (AKI) was attributable. This case suggests that post-HSCT AKI is not necessarily
      accompanied by apparent renal histologic damage, even if it is clinically
      serious.

PMID- 28509242
TI  - Endovascular treatment of renal artery stenosis improves contralateral renal
      hypertrophy with nephrotic syndrome.
AB  - Nephrotic syndrome due to renovascular hypertension is uncommon. We herein report
      a case of nephrotic syndrome associated with unilateral atherosclerotic renal
      artery stenosis. A 76-year-old woman who had been taking antihypertensive
      medication for more than 15 years was referred to our hospital for treatment of
      uncontrolled hypertension and massive proteinuria in the nephrotic range. An
      abdominal bruit was heard, and laboratory findings showed high plasma renin
      activity and hypokalemia. Renal computed tomography angiography showed severe
      stenosis of the ostium of the right renal artery and an atrophic right kidney.
      The left renal artery was normal and the left kidney was compensatorily enlarged.
      After admission, we started treatment with an angiotensin II receptor blocker and
      subsequently performed percutaneous transluminal renal angioplasty with renal
      artery stent placement. As a result, her blood pressure became well controlled
      and the massive proteinuria disappeared. In addition, her stenotic-side renal
      atrophy was resolved, concomitant with an improvement in her renal function. The
      contralateral renal hypertrophy was also resolved.

PMID- 28509241
TI  - A case of encapsulating peritoneal sclerosis presented shortly after renal
      transplantation.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of
      peritoneal dialysis (PD), characterized by extensive intraperitoneal fibrosis and
      encasement of bowel loops. It typically associates with long-term PD and
      progressive loss of ultrafiltration. The management of EPS has evolved
      substantially from the original report of this entity and now includes
      immunosuppressive agents, antifibrotic agents, nutritional support, and surgical
      intervention. Although the exact cause of this condition remains obscure and
      despite the possible positive effect of immunosuppression on EPS, it has been
      described in the post-transplant setting upon the discontinuation of PD. We
      report such a case of a former PD patient who presented with EPS a month after
      renal transplantation. This article will highlight the current views regarding
      the management of post-transplant EPS and introduce the problem of long-term PD
      patients on the deceased-donor transplant waiting list.

PMID- 28509243
TI  - A case of immunoglobulin A nephropathy treated successfully with tonsillectomy
      and steroid pulse therapy 20 years after onset.
AB  - A 46-year-old male was found to have proteinuria on a routine medical examination
      in 1985 at the age of 22 years and was diagnosed with immunoglobulin A (IgA)
      nephropathy by renal biopsy. He regularly visited a hospital, but 3 years later
      made the decision to stop. In 2000, his serum creatinine level was 1.3 mg/dl. His
      renal function then deteriorated, with persistent proteinuria and hematuria,
      following which he visited our hospital in December 2008. A further renal biopsy
      was performed. Active and chronic IgA nephropathy was confirmed histologically,
      with sclerosing lesions also being found. He was treated with three courses of
      steroid pulse therapy in February and tonsillectomy in April 2009. During the
      follow-up period at the outpatient clinic, results for proteinuria and hematuria
      were negative, suggesting that progression of renal impairment had been
      prevented. The efficacy of tonsillectomy plus steroid pulse therapy for early IgA
      nephropathy has been demonstrated, and this treatment was effective in our
      patient 20 years after the onset of the disease.

PMID- 28509244
TI  - Pregnancy in 4 women with childhood-onset steroid-sensitive nephrotic syndrome.
AB  - Four women with childhood-onset steroid-sensitive nephrotic syndrome (SSNS) had 5
      pregnancies. Their age at onset of SSNS was between 4 and 10 years, and age at
      pregnancy was between 21 and 31 years. Three patients with frequent relapsing
      nephrotic syndrome (NS) continued to relapse after 20 years of age. Two of them
      had relapses during 6-32 gestational weeks of pregnancy and were treated with
      prednisolone (PSL) 10-45 mg/day. One patient delivered a normal baby on 2
      pregnancies. Another developed superimposed preeclampsia and her infant showed
      asymmetrical type of intrauterine growth restriction (IUGR). There was no relapse
      during pregnancy in 2 patients, including 1 with frequent relapses, who had no
      relapse over 5 years preceding the pregnancy. In all four patients, normal renal
      function and complete remission were noted at the last follow-up. Their 5 infants
      were well at 1-7 years of age. Although hypertension, growth failure of the
      placenta, and IUGR of the baby may complicate the pregnancy, most pregnancies
      with SSNS seem to result in normal birth, even when relapses occur during
      pregnancy and are treated with PSL.

PMID- 28509245
TI  - Gamma 1-heavy chain deposition disease accompanied by IgG kappa in serum, urine,
      and bone marrow.
AB  - A 32-year-old Japanese woman presented with hypertension, nephrotic syndrome,
      microhematuria, and severe hypocomplementemia. Her serum creatinine concentration
      increased from 1.46 mg/dL (129.0 MUmol/L) to 3.46 mg/dL (305.8 MUmol/L) over 1
      month. Renal biopsy revealed Congo red-negative nodular glomerulosclerosis
      accompanied by mesangial proliferation. There was extensive staining of
      immunoglobulin (Ig) G in the glomerular and tubular basement membranes and
      expanded mesangial regions. Staining was negative for IgA, IgM, and kappa and
      lambda light chains and positive for the gamma 1 IgG subclass. Staining for
      constant domains of the gamma heavy chains showed a deletion of the first
      constant domain (CH1). Electron microscopy revealed electron-dense deposits in
      the glomerular and tubular basement membranes and mesangium. These findings
      indicated gamma 1-heavy chain deposition disease (HCDD). Serum and urine
      immunoelectrophoresis revealed an IgG kappa monoclonal band, whereas bone marrow
      biopsy revealed monoclonal plasmacytosis with positive staining for kappa chains.
      HCDD associated with kappa light chain is extremely rare. We report the first
      case of HCDD with IgG kappa detected in the serum, urine, and bone marrow.

PMID- 28509246
TI  - Garland-pattern postinfectious glomerulonephritis with IgA-dominant deposition.
AB  - A histological subtype of acute postinfectious glomerulonephritis (APIGN), the
      garland pattern, is identified not only by characteristic histological findings,
      but also by severe clinical course as compared with typical APIGN. However, since
      the morbidity of APIGN has decreased globally, there have been few reports on
      this disease form in developed countries during the last two decades. Herein, we
      report a case of adolescent garland-pattern APIGN with IgA-dominant deposits,
      presenting with severe nephrotic syndrome and protracted hematuria and
      proteinuria. We also review the clinical and histological features of 13
      previously reported cases in Japan and compare them with our present case. In our
      review, we confirmed IgA deposition in at least three of these patients, in whom
      urinary protein excretion tended to be greater than those patients without IgA.
      Greater awareness of this condition is necessary to ensure appropriate follow-up
      of the clinical course of patients with garland-pattern APIGN with IgA
      deposition.

PMID- 28509247
TI  - Successful treatment of bortezomib-refractory multiple myeloma derived from
      monoclonal gammopathy of undetermined significance with dose-adjusted
      lenalidomide therapy in a patient with concomitant end-stage renal disease due to
      diabetic nephropathy requiring haemodialysis.
AB  - Malignancy is a fatal complication of end-stage renal disease (ESRD) requiring
      haemodialysis. However, the successful treatment of haematological malignancies
      has been rarely reported. We describe the case of a 63-year-old man who presented
      with IgA-type multiple myeloma (MM; Durie-Salmon stage IIIB) derived from
      monoclonal gammopathy of undetermined significance concomitant with ESRD due to
      diabetic nephropathy. First, haemodialysis was initiated before chemotherapy, and
      bortezomib and dexamethasone were found to be ineffective. Subsequently, 8
      courses of dose-adjusted lenalidomide therapy were administered according to the
      degree of haematological and renal functions. The patient remained in partial
      remission without disease progression for 21 months. Thus, lenalidomide therapy
      is effective for bortezomib-refractory MM concomitant with ESRD.

PMID- 28509248
TI  - Periodic hypokalemia associated with cyclic Cushing's syndrome.
AB  - A 69-year-old woman presented with periodic hypertension, edema, and hypokalemia
      that occurred within an interval of a few weeks. Her laboratory test values
      showed autonomously elevated plasma adrenocorticotropic hormone (ACTH) and
      cortisol concentrations. The patient's Cushingoid features were not evident on
      first admission. Several weeks later, in spite of constant oral potassium
      supplementation, severe hypokalemia recurred with Cushingoid features and
      worsening symptoms of leg edema and pigmentation, which spontaneously disappeared
      within a few days. Her periodic symptoms occurred in parallel with fluctuations
      of plasma ACTH and cortisol concentrations. A series of endocrinological and
      pituitary imaging findings led to a tentative diagnosis of cyclic Cushing's
      syndrome caused by ectopic ACTH secretion. However, chest and abdominal computed
      tomography did not reveal any candidate lesion. The patient's periodic
      hypercortisolemia and symptoms were well controlled after treatment with
      metyrapone plus dexamethasone. This is a very rare case of periodic hypokalemia
      and hypertension caused by cyclic Cushing's syndrome.

PMID- 28509249
TI  - Renal cell carcinoma presenting as AA amyloidosis: a case report and review of
      the literature.
AB  - A 47-year-old Caucasian man developed mild diarrhoea associated with more than 10
      kg weight loss, severe fatigue and anaemia. Endoscopy demonstrated deposits of AA
      amyloid within the gastrointestinal tract. He had heavy proteinuria with a serum
      albumin of 15 g/L consistent with systemic AA amyloidosis. He had no symptoms to
      suggest an underlying chronic inflammatory condition but had CRP 130 mg/L and SAA
      474 mg/L. In an attempt to identify the source of his inflammatory response, he
      underwent a contrast-enhanced whole-body computed tomography scan, which revealed
      a necrotising mass lesion in the right kidney consistent with a renal cell
      carcinoma. It also showed non-mechanical obstruction of the small bowel and,
      immediately post-imaging, the patient developed intractable vomiting followed by
      oliguric renal failure requiring haemodialysis. Despite his renal and gut
      failure, he underwent right radical nephrectomy without further complications.
      Histology showed complete resection of a clear cell renal cell carcinoma and
      renal amyloid deposits. Post-surgery, his acute-phase response decreased to
      normal, consistent with the renal cell carcinoma acting as the inflammatory
      stimulus. Although he remains dialysis dependent, his gut function improved and
      he has regained both normal weight and serum albumin. Our case demonstrates
      partial resolution of AA amyloidosis with removal of the inflammatory source.

PMID- 28509251
TI  - Increased antiangiogenetic factors in severe proteinuria without hypertension in
      pregnancy: is kidney biopsy necessary?
AB  - Acute onset of severe proteinuria during pregnancy obliges physicians to
      clinically discriminate between gestational proteinuria (GP) and new onset of
      nephritis. A multiparous woman developed severe proteinuria (5.8 g/day) without
      hypertension at 32 weeks of gestation. We measured the maternal level of soluble
      fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), which were
      extremely high (41.3 and 54.8 ng/ml, respectively), leading us to consider this
      condition as GP rather than acute onset of nephritis. Thus, we did not perform a
      kidney biopsy and did not administer a steroid agent. Non-reassuring fetal status
      required emergency Cesarean section at 33 weeks. Proteinuria decreased to 0.36
      g/day at 12 weeks after delivery, and finally disappeared 26 weeks postpartum.
      Measurement of sFlt-1 and sEng in a pregnant woman with severe proteinuria
      without hypertension may assist in differential diagnosis of GP from acute onset
      of nephritis, and thus help to decide whether to perform kidney biopsy during
      pregnancy.

PMID- 28509250
TI  - Prerenal uremia induced by severe diarrhea due to colon adenoma: a case of
      McKittrick-Wheelock syndrome in an elderly patient.
AB  - McKittrick-Wheelock syndrome can be successfully treated by emergent dialysis,
      prescription of bicarbonate, and endoscopic submucosal dissection, which allow
      elderly people suffering from this syndrome to maintain their activities of daily
      living. In patients with this syndrome, a large colonic villous adenoma secretes
      excessive amounts of mucus and causes severe electrolyte depletion and
      dehydration. An 81-year-old man who had been suffering from chronic renal failure
      (creatinine 256.4 MUmol/L), hypertension, and arrhythmia presented with frequent
      mucous diarrhea for a month. He was hospitalized for appetite loss, vomiting,
      general fatigue, and acute renal failure. His blood tests and blood gas analysis
      revealed urea nitrogen 58.9 mmol/L, creatinine 954.7 MUmol/L, pH 7.13, and a base
      excess of -20.1 mmol/L. Although his symptoms were improved by the emergent
      dialysis and rehydration, he suffered a relapse only 4 days after he was
      discharged. At the second admission, a near-circumferential tumor was found in
      the rectum by the colonoscopy, which was pathologically confirmed as a villous
      adenoma. Considering his age and complications, endoscopic submucosal dissection
      was selected, and internal use of sodium bicarbonate was prescribed. Diarrhea and
      appetite loss were improved by these treatments, and the creatinine level was
      also improved to 168.0 MUmol/L.

PMID- 28509252
TI  - Renal vein thrombosis associated with oral contraception and smoking: a case
      report from Japan, with literature review.
AB  - Renal vein thrombosis, one of the common thrombotic complications of nephrotic
      syndrome or renal cell carcinoma, is reportedly a rare complication of hormonal
      contraception. Solitary renal vein thrombosis in the Japanese population is
      thought to be very rare because the incidence of venous thromboembolism is
      comparatively very low in Asian populations. We report a 38-year-old Japanese
      female with left renal vein thrombosis associated with oral contraception and
      concurrent smoking as the first Japanese case of solitary renal vein thrombosis
      associated with oral contraceptives, with a review of the literature. Seven cases
      were previously reported. The results revealed that all patients complained of
      acute onset of pain around the involved kidney without urinary symptoms or fever,
      and were effectively treated with anticoagulants. Other remarkable facts include
      that nausea and vomiting were frequently seen, and that the renal outcome was
      benign, despite various initial urine abnormalities. This report may alert
      clinicians to the importance of these risk factors as an etiology of renal vein
      thrombosis even in Asian populations. Clinicians should regard renal vein
      thrombosis as one of the differential diagnoses for acute flank pain in patients
      using oral contraceptives. A detailed history taking that reveals oral
      contraception, smoking, and other thrombophilic predispositions as well as timely
      computed tomographic scans would be the keys to diagnosis. Smoking cessation
      should be strongly recommended to oral contraceptive users, especially women over
      35 years of age, regardless of dosage.

PMID- 28509253
TI  - Membranous nephropathy secondary to Graves' disease with deposits of thyroid
      peroxidase in an adult.
AB  - A 40-year-old woman was diagnosed with Graves' disease in 2001 and treated with
      thiamazole, but disease control was poor. She was referred to our hospital in
      2011 for exacerbation of proteinuria, which had been present since 2006.
      Urinalysis showed a protein/creatinine ratio of 4.2 g/gCre and microhematuria,
      and a renal biopsy was performed. On electron microscopy, high electron density
      deposits were seen on the epithelial side of the glomerular basement membrane.
      IgG was also deposited along the glomerular loop wall, and membranous nephropathy
      was diagnosed. Immunostaining revealed thyroid peroxidase deposits but not
      thyroglobulin antigen deposits, suggesting that the membranous nephropathy was
      secondary to Graves' disease. The membranous nephropathy improved with 131I
      treatment. To our knowledge, this is the first adult case of membranous
      nephropathy originating from Graves' disease in which deposits of thyroid
      peroxidase antigens have been detected.

PMID- 28509254
TI  - Effect of eculizumab and recombinant human soluble thrombomodulin combination
      therapy in a 7-year-old girl with atypical hemolytic uremic syndrome due to anti
      factor H autoantibodies.
AB  - Atypical hemolytic uremic syndrome (aHUS), which is defined as non-Shiga toxin
      associated hemolytic uremic syndrome, is a type of thrombotic microangiopathy.
      This syndrome presents with hemolytic anemia, thrombocytopenia, and acute kidney
      injury. Excessive complement activation due to genetic disorders of the
      complement system or production of autoantibodies to factor H (FH) causes the
      disease. We report a successful treatment course using eculizumab and recombinant
      human soluble thrombomodulin (rTMD) for a 7-year-old girl with aHUS due to anti
      FH autoantibodies. Although her chief complaints were abdominal pain and loose
      stools, we were finally able to diagnose her with aHUS because Shiga toxin
      producing Escherichia coli was not detected in her feces and a hemolytic assay
      analyzing FH function was positive. We administrated rTMD to our patient because
      of signs of disseminated intravascular coagulation. Soon after the therapeutic
      intervention, the platelet count began to increase and abdominal pain was
      moderately improved. Plasma exchange limited the efficacy of her disease.
      Therefore, we administered eculizumab, monoclonal humanized antibody against C5,
      3 weeks after admission. Platelet counts immediately increased and kidney
      function gradually recovered. Genetic disorders were not detected. However, anti
      FH autoantibody was observed. There were no symptoms for recurrence of aHUS or
      kidney dysfunction for 15 months, as a result of the administration of eculizumab
      every other week. In conclusion, combination therapy of eculizumab and rTMD was
      effective for an aHUS patient. This therapy may be helpful for improving the
      prognosis and long-term kidney function of aHUS patients.

PMID- 28509255
TI  - Five cases of tonsillectomy and steroid pulse therapy for recurrent
      immunoglobulin A nephropathy after kidney transplantation.
AB  - Five cases of recurrent immunoglobulin A nephropathy (IgAN) after kidney
      transplantation were successfully treated by tonsillectomy and steroid pulse
      therapy (SPT). The clinical background and pathology in the five cases were
      different, but good results were obtained in all of them. In cases 1 and 2, mild
      recurrent IgAN developed and failed to remit after tonsillectomy alone, but a
      remission was achieved in both cases after SPT. In case 3, highly active
      recurrent IgAN with crescent lesions developed 13 years after kidney
      transplantation, and a remission was achieved after SPT. In case 4, renal biopsy
      specimens showed pathological findings of recurrent IgAN with tubulitis, and
      hematuria and proteinuria resolved after SPT. In case 5, the biopsy findings
      indicated recurrent IgAN with chronic rejection. Tonsillectomy was followed by
      resolution of the proteinuria, and a remission was achieved after SPT. In
      conclusion, SPT is effective in inducing a remission of recurrent IgAN when
      tonsillectomy alone fails.

PMID- 28509256
TI  - Long-term prognosis of 4 children with steroid-sensitive nephrotic syndrome and
      relapse after 30 years of age.
AB  - Some children with steroid-sensitive nephrotic syndrome (SSNS) have been reported
      to suffer relapses in adulthood, but the clinical course of such adults is
      unclear. Four children with SSNS suffered relapses after 30 years of age. Those 4
      patients developed frequently relapsing nephrotic syndrome (NS) between 2 and 10
      years of age. They were treated with prednisolone (PSL) combined with
      cyclophosphamide in 3 patients, mizoribine in 2, and cyclosporine in 1 during
      childhood, and with cyclosporine in 2 during adulthood. After 20 years of age,
      the frequency of relapses gradually decreased. The last relapse occurred between
      33 and 39 years of age, and proteinuria disappeared within 1 month after the
      start of treatment with PSL. At the last follow-up, all 4 patients continued to
      receive PSL, had normal renal function, and were in complete remission of NS when
      they were between 33 and 41 years of age. Although the long-term outcome of SSNS
      is usually considered to be favorable, pediatricians should be aware that some
      children with SSNS may require long-term treatment during adulthood.

PMID- 28509257
TI  - A case of antiglomerular basement membrane glomerulonephritis complicated by
      membranous nephropathy.
AB  - The sequential or simultaneous presentation of anti-glomerular basement membrane
      (anti-GBM) glomerulonephritis with membranous nephropathy (MN) has been
      infrequently reported. Although the mechanism underlying MN superimposed on anti
      GBM glomerulonephritis is unknown, the two entities are believed to be
      interrelated. We report the case of a 75-year-old woman diagnosed with rapidly
      progressive glomerulonephritis. Renal biopsy revealed crescentic
      glomerulonephritis with linear and granular staining of immunofluorescent IgG1
      and IgG4 granular staining on the capillary loops. Electron microscopy revealed
      extensive subepithelial deposits. These findings suggested simultaneous
      development of anti-GBM glomerulonephritis and MN in this case. Serum
      phospholipase A2 receptor (PLA2R) antibody was negative. The patient was treated
      with prednisolone and plasma exchange, resulting in resolution of renal
      insufficiency and a decrease in urinary protein. The rapid decrease in urinary
      protein and absence of PLA2R antibody suggest that the mechanism of MN associated
      with anti-GBM glomerulonephritis differs from that of primary MN.

PMID- 28509258
TI  - AP-VAS 2012 case report: an atypical case of microscopic polyangiitis presenting
      with acute tubulointerstitial nephritis without glomerular change.
AB  - Renal involvement in myeloperoxidase-antineutrophil cytoplasmic antibody (MPO
      ANCA)-associated vasculitis is frequently characterized by focal segmental
      crescentic and/or necrotizing glomerulonephritis. However, a few cases of only
      tubulointerstitial nephritis (TIN) involvement without any apparent glomerular
      lesions have been reported. Here we report just such a case. A 74-year-old woman
      was admitted to a nearby hospital with a 2-week history of pitting edema, fever
      and anemia. She developed acute renal failure without proteinuria and microscopic
      hematuria. The urinary excretion of N-acetyl-beta-D-glucosaminidase and beta2
      microglobulin concentration were 30.3 U/ml and 42270 MUg/ml, respectively.
      Gallium-67 scintigraphy revealed abnormal concentrations on both sides of her
      kidneys. Her MPO-ANCA titer was 92 EU (normal range <10 EU). Skin and renal
      biopsies demonstrated fibrinoid vasculitis, necrotizing angiitis and TIN without
      glomerular change. Microscopic polyangiitis was diagnosed based on clinical and
      pathological criteria. No other factor that could induce TIN was detected. This
      case illustrates an unusual renal presentation of acute renal failure due to
      necrotizing arteritis and TIN, consistent with MPO-ANCA-associated vasculitis
      lacking crescentic glomerulonephritis. The pathogenesis is currently unclear, but
      the low-affinity type of MPO-ANCA was identified.

PMID- 28509259
TI  - Moran-type bounds for the fixation probability in a frequency-dependent Wright
      Fisher model.
AB  - We study stochastic evolutionary game dynamics in a population of finite size.
      Individuals in the population are divided into two dynamically evolving groups.
      The structure of the population is formally described by a Wright-Fisher type
      Markov chain with a frequency dependent fitness. In a strong selection regime
      that favors one of the two groups, we obtain qualitatively matching lower and
      upper bounds for the fixation probability of the advantageous population. In the
      infinite population limit we obtain an exact result showing that a single
      advantageous mutant can invade an infinite population with a positive
      probability. We also give asymptotically sharp bounds for the fixation time
      distribution.

PMID- 28509261
TI  - Management of fracture dorso-lumbar spine in a pregnant female by surgery in
      prone position.
AB  - Surgical management of thoraco-lumbar spine fracture in pregnancy has specific
      concerns during surgery like positioning, approach, and radiation exposure to
      fetus. We report a case of burst fracture of 12th thoracic vertebrae with
      paraplegia in a young female with 26 weeks of gestation. Surgery was performed in
      prone position on a Toronto frame. This report also discusses the management of
      thoraco-lumbar spine fracture in pregnancy with review of literature.

PMID- 28509260
TI  - Rapid Serum-Free Isolation of Oligodendrocyte Progenitor Cells from Adult Rat
      Spinal Cord.
AB  - Oligodendrocyte progenitor cells (OPCs) play a pivotal role in both health and
      disease within the central nervous system, with oligodendrocytes, arising from
      resident OPCs, being the main myelinating cell type. Disruption in OPC numbers
      can lead to various deleterious health defects. Numerous studies have described
      techniques for isolating OPCs to obtain a better understanding of this cell type
      and to open doors for potential treatments of injury and disease. However, the
      techniques used in the majority of these studies involve several steps and are
      time consuming, with current culture protocols using serum and embryonic or
      postnatal cortical tissue as a source of isolation. We present a primary culture
      method for the direct isolation of functional adult rat OPCs, identified by
      neuron-glial antigen 2 (NG2) and platelet derived growth factor receptor alpha
      (PDGFralpha) expression, which can be obtained from the adult spinal cord. Our
      method uses a simple serum-free cocktail of 3 growth factors - FGF2, PDGFAA, and
      IGF-I, to expand adult rat OPCs in vitro to 96% purity. Cultured cells can be
      expanded for at least 10 passages with very little manipulation and without
      losing their phenotypic progenitor cell properties, as shown by
      immunocytochemistry and RT-PCR. Cultured adult rat OPCs also maintain their
      ability to differentiate into GalC positive cells when incubated with factors
      known to stimulate their differentiation. This new isolation method provides a
      new source of easily accessible adult stem cells and a powerful tool for their
      expansion in vitro for studies aimed at central nervous system repair.

PMID- 28509262
TI  - A case of cryopyrin-associated periodic syndrome with kidney transplant failure.
AB  - The cryopyrin-associated periodic syndrome (CAPS) is an autosomal dominant
      autoinflammatory disease characterized by fever, skin rash, and joint involvement
      with acute inflammatory response. The genetic defect involves the NLRP3 gene that
      encodes cryopyrin and leads to an abnormal production of interleukin-1 (IL-1).
      Therefore, anti-IL-1 treatment represents an effective therapy. One of the most
      severe manifestations of the disease is secondary amyloidosis that causes renal
      failure. We present a patient with CAPS who underwent renal transplantation for
      renal insufficiency caused by amyloidosis. The function of the transplanted
      kidney deteriorated because of the late administration of IL-1 receptor
      antagonist, anakinra. This case may indicate the importance of early initiation
      of anti-IL-1 treatment in CAPS patients who have undergone kidney
      transplantation.

PMID- 28509263
TI  - Atopic dermatitis, cyclosporine, and nephrotoxicity.

PMID- 28509264
TI  - A case of membranoproliferative glomerulonephritis and AA amyloidosis complicated
      with pulmonary nontuberculous mycobacterial infection.
AB  - A 75-year-old man was diagnosed with pulmonary nontuberculous mycobacterial (NTM)
      infection in February 2005 and was treated with rifampicin, ethambutol, and
      clarithromycin. However, the infection was resistant to treatment, and his chest
      radiograph showed an abnormality that gradually seemed to aggravate. The
      patient's sputum was positive for Mycobacteria. Moreover, the patient had dyspnea
      and an underlying chronic inflammation in the lungs. He visited our hospital
      because of dyspnea and leg edema in June 2011. Laboratory evaluation on admission
      revealed proteinuria (6 g/day) and decreased serum total protein (5.8 g/dL) and
      albumin (1.6 g/dL) levels, indicating nephrotic syndrome. Percutaneous renal
      biopsy revealed membranoproliferative glomerulonephritis (MPGN) in the acute
      stage and AA amyloidosis of mild degree. AA amyloidosis was also diagnosed
      histologically on gastric and colonic biopsy, in addition to renal biopsy. His
      renal function decreased gradually, and therefore, he underwent hemodialysis
      therapy in January 2012. However, his gastrointestinal-related symptoms
      persisted, and his appetite diminished, because of which he had become severely
      malnourished; he died 8 months later. This is a rare case of a patient with two
      different renal lesions (MPGN and AA amyloidosis) complicated with NTM. Our case
      suggests that MPGN and amyloidosis should be considered in elderly patients with
      nephrotic syndrome onset and chronic inflammation.

PMID- 28509265
TI  - Hepatitis C virus-related glomerulonephritis with acute kidney injury requiring
      hemodialysis that improved with virus removal and eradication using double
      filtration plasmapheresis without interferon.
AB  - A 66-year-old, hepatitis C virus (HCV)-positive woman was admitted to our
      hospital with oliguria, systemic edema, and rapid deterioration of renal
      function. Laboratory examination showed increased serum creatinine and decreased
      serum albumin levels, complement activity, and cryoglobulin positivity. The HCV
      RNA genotype was found to be 1b, and the viral load was high. Kidney biopsy
      examination showed type I membranoproliferative glomerulonephritis with capillary
      deposition of IgM and C3, indicating HCV-related glomerulonephritis. After
      hospitalization, hemodialysis was immediately required because of uremia and
      oliguria. Her renal function did not improve despite corticosteroid therapy. To
      treat the increasing HCV load, virus removal and eradication by double-filtration
      plasmapheresis therapy without interferon was performed, since the patient was
      allergic to interferon therapy. This treatment improved renal function and
      allowed the withdrawal from hemodialysis. This report presents a case of
      successful VRAD without interferon therapy in a patient with HCV-related
      glomerulonephritis and acute kidney injury that required hemodialysis.

PMID- 28509266
TI  - A case of gefitinib-associated membranous nephropathy in treatment for pulmonary
      adenocarcinoma.
AB  - We experienced a case that was considered as gefitinib-associated membranous
      nephropathy (MGN) in treatment for pulmonary adenocarcinoma. A female patient
      aged 80 who had been treated for lung cancer was referred and hospitalized at our
      hospital, because of nephrotic syndrome. The patient had pulmonary adenocarcinoma
      (cT4N2M1a) with positive for epidermal growth factor receptor (EGFR) mutation.
      Gefitinib, EGFR tyrosine kinase inhibitor, was initiated from 1 year and 2 months
      ago. At that time, proteinuria was negative. The treatment effect on lung cancer
      was so favorable that partial response had been maintained. However, from 4
      months ago, edema of legs appeared, leading to become nephrotic syndrome. Renal
      biopsy was performed, and secondary MGN was diagnosed, because of deposition of
      peripheral IgG, mesangial IgA, and C3, as well as the deposition of peripheral
      IgG4, IgG1, IgG2, and weak IgG3. We considered drug-induced MGN and discontinued
      the administration of gefitinib. Subsequently, the proteinuria tended to decrease
      gradually and became negative 10 months later. However, the lung cancer recurred
      3 months after discontinuation of gefitinib and another molecular target drug,
      erlotinib, was administered. At present, 13 months after discontinuation of
      gefitinib, absence of proteinuria is maintained. It has been generally considered
      that secondary MGN can be induced by both malignant tumor and their treatment. In
      the present case, the clinical course and pathological characteristics showed the
      secondary MGN that might be associated with gefitinib during the treatment for
      pulmonary adenocarcinoma. The present case, to our knowledge, may be a first case
      of gefitinib-associated MGN.

PMID- 28509267
TI  - A hospital-acquired outbreak of catheter-related nontuberculous mycobacterial
      infection in children on peritoneal dialysis.
AB  - Catheter-related nontuberculous mycobacterial infection in children with chronic
      renal failure on peritoneal dialysis (PD) is rare. However, there have been five
      such infections in infants among PD patients at our center. Although the patients
      were treated with antibiotics to which the organisms showed in vitro sensitivity,
      they were clinically drug resistant. Hence, all PD catheters needed to be
      removed. Thereafter, following hemodialysis treatment for approximately 1 month,
      the PD catheters were replaced, with no recurrence of infection. On investigation
      of the infection route, it was found that these bacteria had colonized around a
      shower head in one of the bathrooms. These findings suggest that, in cases where
      hot water systems at hospitals are considered at a high risk, frequent
      sterilization is needed, especially around the shower heads. It is also necessary
      to reconsider current standard practices in the management of catheter exit
      sites, especially if the national incidence of infection increases.

PMID- 28509268
TI  - Pulmonary hemorrhage associated with Henoch-Schoenlein purpura in an adult
      patient primary diagnosed of IgA nephropathy.
AB  - We describe a case of IgA nephropathy (IgAN) followed by pulmonary hemorrhage
      associated with Henoch-Schoenlein purpura (HSP) in an adult female. The patient
      had a history of renal insufficiency and persistent hematuria and proteinuria,
      without any extra-renal involvement. She was diagnosed with IgAN 7 years before
      the onset of HSP and had received immunosuppressive therapy for 6 years. One year
      after discontinuing oral prednisolone and mizoribine, she suffered a pulmonary
      hemorrhage. She presented with exacerbated urinary findings, and palpable
      purpura, resulting in the diagnosis of HSP. Intravenous pulse methylprednisolone
      followed by oral prednisolone (1 mg/kg/day) and a monthly intravenous
      cyclophosphamide pulse resolved the pulmonary hemorrhage. In a review of 36 HSP
      patients complicated with pulmonary hemorrhage, 27.8 % of the patients perished
      [Rajagopala et al., Semin Arthritis Rheum 42:391-400, 1]. While the most
      efficient therapeutic strategies for these patients have yet to be determined, we
      speculate that an aggressive therapy of pulse methylprednisolone combined with
      immunosuppression agents is likely to bring about the best outcome in cases with
      pathological conditions similar to our patient's. On the other hand,
      discontinuance of immunosuppressive therapy might have resulted in the
      aggravation of the disease, hence we should examine patients carefully not to
      miss the cue.

PMID- 28509269
TI  - De novo myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated
      glomerulonephritis 31 years after living-donor kidney transplantation.
AB  - A 61-year-old woman was admitted to our hospital because of an unexpected rise in
      serum creatinine (sCr) level with proteinuria and microhematuria. She had
      undergone living-donor kidney transplantation 31 years before for end-stage renal
      disease caused by chronic glomerulonephritis (GN). On admission, her sCr was 1.27
      mg/dL which was increased from 0.6 mg/dL, urinary protein/creatinine ratio was
      1.39 g/gCr, and urinary red blood cell count was more than 100 per high power
      field. The allograft biopsy revealed crescentic glomerulonephritis with moderate
      to severe tubulointerstitial inflammation. Immunofluorescence staining yielded
      only a minimal staining for immunoglobulin A, and negative C4d in peritubular
      capillary. Since increased myeloperoxidase-antineutrophil cytoplasmic antibody
      (MPO-ANCA) titer of 45.5 U/mL was detected, we made the diagnosis of post
      transplant MPO-ANCA-associated GN. She was treated with three doses of bolus
      methylprednisolone (500 mg) followed by oral prednisolone therapy. Her sCr was
      stable at 1.20 mg/dL thereafter. ANCA-associated GN should be considered in older
      kidney transplant patients with new-onset urinary abnormalities because typical
      systemic symptoms and vasculitis in other organs might be masked by maintenance
      immunosuppression.

PMID- 28509270
TI  - Uterus didelphys with obstructed hemivagina and contralateral multicystic
      dysplastic kidney.
AB  - Mullerian anomalies are often associated with urinary tract anomalies. Herlyn
      Werner-Wunderlich syndrome or obstructed hemivagina and ipsilateral renal anomaly
      are rare Mullerian anomaly comprising uterine didelphys, obstructed hemivagina,
      and ipsilateral renal anomaly. We report an unusual case of uterus didelphys with
      obstructed hemivagina and contralateral (not ipsilateral) multicystic dysplastic
      kidney. An early diagnosis is critical to prevent complications such as adhesions
      with subsequent infertility. A careful evaluation of the female reproductive
      tract may be necessary in children with not only renal aplasia but also lateral
      renal anomalies such as multicystic dysplastic kidney.

PMID- 28509271
TI  - Preeclampsia before 20 weeks of gestation: a case report and review of the
      literature.
AB  - The occurrence of preeclampsia before 20 weeks of gestation is rare and usually
      associated with trophoblastic diseases or antiphospholipid syndrome. Here, we
      report a case of preeclampsia before 20 weeks of gestation in the absence of the
      aforementioned disorders. A healthy 30-year-old nulliparous woman presented with
      new onset of hypertension and proteinuria at 18 weeks of gestation. Fetal
      ultrasound did not reveal any abnormalities. Empirical steroid treatment was
      initiated based on a tentative diagnosis of underlying renal disease. The
      clinical course of the disease was progressive despite steroid treatment and the
      fetus died in utero 8 days after the initiation of treatment. Following delivery,
      a renal biopsy was performed and provided a diagnosis of preeclampsia. All
      symptoms resolved postpartum. This report demonstrates that preeclampsia may
      occur before 20 weeks of gestation and should always be considered in the
      differential diagnosis of pregnant women with new onset of hypertension with
      proteinuria. Previous published cases are summarized briefly.

PMID- 28509272
TI  - An unusual association between focal segmental sclerosis and lupus nephritis: a
      distinct concept from lupus podocytopathy?
AB  - Lupus nephritis (LN) is usually associated with immune deposition in the
      glomerular capillary wall. On the other hand, focal segmental glomerulosclerosis
      (FSGS) is not typically associated with immune deposition, and its pathogenesis
      includes podocyte damage and loss. The definition of lupus podocytopathy (LP)
      excludes patients with electron-dense glomerular basement membrane deposits.
      Here, we report the case of an LN patient with nephrotic proteinuria. Renal
      pathology demonstrated focal endocapillary hypercellularity superimposed on foam
      cells. Immunofluorescence revealed diffuse global subepithelial immune deposits,
      and electron microscopy showed electron-dense glomerular basement membrane
      deposits and diffuse foot process effacement. Treatment with steroid and
      cyclosporine improved her proteinuria. Post-treatment renal re-biopsy revealed
      focal segmental sclerotic lesions closely resembling FSGS. These results indicate
      that the pathogenesis of this case may involve an FSGS-like condition or
      podocytopathic change. It is possible that careful examination would reveal
      podocytopathic changes other than LP in patients previously diagnosed as LN class
      III + V. Further investigations are needed to understand FSGS-like pathological
      changes accompanied with capillary immune deposits in LN.

PMID- 28509273
TI  - Post-infectious acute glomerulonephritis with vasculitis and pulmonary
      hemorrhage.
AB  - An 84-year-old male complained of fever, cough, sputum, and appetite loss. His
      renal function rapidly worsened, and he had hypoalbuminemia and
      hypocomplementemia. His condition worsened and C-reactive protein levels were
      elevated. Vasculitis syndrome was suspected and he was administered 40 mg of
      prednisolone, although myeloperoxidase antineutrophil cytoplasmic antibody
      (ANCA), proteinase-3 ANCA and antiglomerular basement membrane antibody tests
      were negative. His body temperature decreased and fatigue promptly resumed. On
      renal biopsy, light microscopy revealed endocapillary and extracapillary
      glomerulonephritis. Vasculitis was detected in interlobular arteries.
      Immunofluorescence studies revealed granular deposits of C3 and IgG along
      capillary walls. Electron microscopy revealed dome-shaped small electron-dense
      granular subepithelial deposits. Acute post-infectious glomerulonephritis was
      suspected. Although his renal function improved, he developed hemoptysis and was
      diagnosed with pulmonary hemorrhage. He received methylprednisolone and plasma
      exchange, and his respiratory status improved gradually. This is an extremely
      rare case and suggests the importance of considering a differential diagnosis.

PMID- 28509274
TI  - Lymphoproliferative disease-related mixed cryoglobulinemia treated with rituximab
      and prednisolone.
AB  - Mixed cryoglobulinemia is often associated with hepatic C virus infection and is
      less common with hepatitis B virus infection, and it often progresses into
      lymphoproliferative diseases. Rituximab is known to achieve systemic B-cell
      depletion and clinical remission of the systemic effects of cryoglobulins in
      hepatitis C virus-associated cryoglobulinemia. Conversely, there are few reports
      regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia.
      We report here the case of a 65-year-old Japanese female who presented with
      lymphoproliferative disease-related cryoglobulinemia with hepatitis B virus,
      including membranoproliferative glomerulonephritis with renal failure. The
      vasculitis was refractory to conventional and antiviral therapy, but rituximab
      use led to control the disease. Our case highlights the benefit and efficacy of
      rituximab in association with antiviral therapy in small vessel vasculitis
      related to lymphoproliferative disease-related cryoglobulinemia with hepatitis B
      virus.

PMID- 28509275
TI  - A case of acute interstitial nephritis and granulomatous hepatitis induced by
      ingesting quinine.
AB  - Quinine is used for the treatment of malarial infection, though not in common
      use. It is especially valuable for the parenteral treatment of severe illness
      owing to drug-resistant strains of Plasmodium falciparum. Quinine is also known
      to occasionally cause acute renal failure (ARF). Although quinine is listed in
      some reviews as a cause of acute interstitial nephritis, most cases of quinine
      associated acute renal failure have been attributed to the hemolytic-uremic
      syndrome (HUS). Only two cases of acute renal failure due to acute interstitial
      nephritis associated with quinine have been reported [1, 2]. To our knowledge,
      there have been 6 reported cases of quinine-induced hepatic granuloma [3-8]. We
      report a case of quinine-induced acute interstitial nephritis (AIN) along with
      granulomatous hepatitis, both of which were confirmed on biopsy. A 50-year-old
      Nigerian man was admitted to the hospital with complaints of fever and general
      fatigue. He had been prescribed quinine as an antimalarial drug in a Nigerian
      hospital. The patient was febrile and showed nonoliguric ARF and liver
      dysfunction. In this case, liver injury showed gradual and spontaneous resolution
      after discontinuing quinine, and ARF resolved after treatment with oral
      prednisolone.

PMID- 28509276
TI  - A case of anaphylactoid reaction to acetate in acetate-containing bicarbonate
      dialysate.
AB  - A 35-year-old man with end-stage kidney disease due to chronic glomerulonephritis
      was admitted to our hospital to start maintenance hemodialysis (HD). One hour
      after starting the first session of HD, he experienced general pruritus,
      urticaria, and dyspnea. Signs and symptoms were resolved by discontinuing HD and
      administrating an antihistamine drug; HD-associated anaphylactoid reactions were
      therefore suspected. Over the next few HD sessions, we changed the dialysis
      membrane, anticoagulant, HD circuit and needle, in that order, but general
      pruritus and urticaria again appeared within 3 h after starting each session of
      HD. Finally, when we changed the dialysate from acetate-containing bicarbonate
      dialysate to acetate-free bicarbonate dialysate, urticaria was clearly less than
      that seen in previous HD sessions, and subsided after discontinuation of HD.
      Subsequently, 20 mg of oral prednisolone (PSL) was administered 1 h before
      starting HD, and the patient did not experience general pruritus, urticaria, or
      dyspnea after starting the session. When administered acetate-containing
      bicarbonate dialysate after oral PSL pretreatment, the patient again experienced
      general pruritus, urticaria and dyspnea. Few reports have been published on the
      occurrence of anaphylactoid reactions during HD using acetate dialysate. We
      report a rare case of anaphylactoid reactions with acetate in acetate-containing
      bicarbonate dialysate that were reduced with the use of acetate-free bicarbonate
      dialysate and oral PSL pretreatment.

PMID- 28509277
TI  - Two brothers with collagenofibrotic glomerulopathy.
AB  - Collagenofibrotic glomerulopathy is a rare glomerular disease characterized by
      extensive accumulation of atypical type III collagen fibers within the mesangial
      matrix and subendothelial space. Laboratory evaluation of this disease shows a
      marked increase in serum procollagen III peptide (P III P) levels. Here, we
      report the case of two brothers with collagenofibrotic glomerulopathy confirmed
      by histology. Patient 1 presented with proteinuria and hypertension and patient 2
      presented with nephrotic-range proteinuria. Immunohistochemistry revealed strong
      staining for antibodies to type III collagen in the widened subendothelial spaces
      in both patients. Electron microscopy revealed numerous collagenous fibers in the
      mesangium and subendothelial space. P III P levels were elevated in both
      patients. Most reported cases of collagenofibrotic glomerulopathy, including the
      adult-onset type, have been sporadic. Within the limits of our literature search,
      this is only the third report of adult siblings with collagenofibrotic
      glomerulopathy confirmed by histology. This report indicates that it may be
      beneficial to measure serum P III P levels in the siblings of patients diagnosed
      with adult-onset collagenofibrotic glomerulopathy.

PMID- 28509278
TI  - A case of post-pneumococcal acute glomerulonephritis with glomerular depositions
      of nephritis-associated plasmin receptor.
AB  - We report the case of a 12-year-old girl who was referred to our hospital with
      anuria associated with pneumonia. On admission, the patient's blood test results
      revealed severe renal failure, hypoproteinemia, and hypocomplementemia. Her
      urinalysis results revealed hematuria, proteinuria, and a positive titer for
      Streptococcus pneumoniae. S. pneumoniae was also detected in her sputum and blood
      cultures. The patient was diagnosed with post-pneumococcal acute
      glomerulonephritis (AGN) with acute renal failure. A renal biopsy demonstrated
      the infiltration of neutrophils and mononuclear cells into capillary loops.
      Immunofluorescence studies showed dominant-positive deposition of C3c along the
      capillary loops and nephritis-associated plasmin receptor (NAPlr) depositions in
      the mesangial area and capillary loops. Electron microscopy revealed dense
      deposits in the glomerular basement membrane without a hump in the subepithelial
      area. These findings were consistent with endocapillary proliferative
      glomerulonephritis. AGN associated with pneumococcal infection is very rare. This
      case suggests that NAPlr is the causative antigen not only of post-streptococcal
      AGN, but also of post-pneumococcal AGN. To our knowledge, this is the first
      report that shows a relationship between post-pneumococcal AGN and NAPlr
      depositions in the glomeruli.

PMID- 28509279
TI  - A case of "hidden" diabetic nephropathy diagnosed by a combination of renal
      biopsy findings and continuous glucose monitoring system.
AB  - Although diabetic nephropathy is a microvascular complication of diabetes
      mellitus, some reports suggest that renal biopsy often shows this pathological
      change without a diagnosis of diabetes mellitus. Here, we report a case of a 65
      year-old man who presented with proteinuria, hypoalbuminemia and hypertension
      without a diagnosis of diabetes mellitus. He drank alcohol regularly and was a
      heavy smoker. Renal biopsy revealed a diffuse increase in the mesangial area,
      mesangial nodules or well-developed hyalinosis, interstitial fibrosis, and
      arteriosclerosis consistent with the changes of diabetic nephropathy. Although we
      had initially diagnosed him with idiopathic nodular glomerulosclerosis, use of a
      continuous glucose monitoring system (CGMS) revealed that the changes in his
      daily blood glucose concentrations met with the diagnostic criteria of diabetes
      mellitus. Accordingly, we diagnosed him with diabetic nephropathy and initiated
      treatment for diabetes mellitus. This case suggests that some cases of diabetic
      nephropathy may be hidden among patients with impaired glucose tolerance, who are
      not diagnosed with diabetes mellitus. Use of a CGMS may be helpful in diagnosing
      this type of "hidden" diabetes mellitus. In addition to diet therapy, smoking
      control, treatment for hypertension, and strict control of hyperglycemia may be
      important for these patients.

PMID- 28509280
TI  - A case of acute kidney injury and disseminated intravascular coagulation
      associated with influenza B viral infection.
AB  - There are few reports of acute kidney injury (AKI) associated with influenza
      viral infection. We treated a case of AKI that developed after an influenza B
      viral infection. A 35-year-old man visited a local physician for a fever and was
      diagnosed with influenza B. He was prescribed laninamivir, then returned to the
      physician 5 days later with dyspnea and was referred to Hospital A. Upon
      admission, respiratory arrest developed, for which he received tracheal
      intubation and mechanical ventilation. AKI was noted after admission and the
      patient was transferred to our hospital the next day. AKI and disseminated
      intravascular coagulation (DIC) were present at the time of transfer, thus a
      transfusion and continuous hemodiafiltration (CHDF) were performed, and
      administrations of thrombomodulin alpha and antithrombin III were initiated.
      Although the patient had DIC, AKI, and disturbance of consciousness, and was in a
      clinical state resembling influenza-associated encephalopathy, there was no clear
      abnormality shown in CT scans of the head. Urine output, renal function, and
      respiratory condition gradually improved, thus CHDF was stopped and extubation
      performed. The patient had no complications and was discharged on hospital day
      22. Some reports have been presented regarding cases of AKI due to rhabdomyolysis
      associated with influenza viral infection, whereas our patient developed AKI as a
      complication of an influenza B viral infection without rhabdomyolysis or
      hemolytic uremic syndrome. Influenza B may cause AKI and DIC, and affected
      patients can be in a serious condition requiring immediate attention.

PMID- 28509281
TI  - Henoch-Schonlein purpura complicated with severe gastrointestinal bleeding.
AB  - Bleeding from the gastrointestinal tract is one of the common determinants of
      morbidity and mortality in the ordinary clinical setting. The gastrointestinal
      involvement of Henoch-Schonlein purpura (HSP) has often been described as self
      limiting, with no long-term morbidity. In this report, we describe our experience
      with a male HSP patient who presented with abdominal pain, loss of appetite and
      deteriorated renal function associated with nephrotic syndrome. Despite the use
      of aggressive immunomodulatory treatments, including corticosteroids and
      plasmapheresis, he developed lethal gastrointestinal hemorrhage. We believe that
      the accumulation of more experience with additional cases similar to ours is
      mandatory for the establishment of optimal management for HSP patients with
      severe gastrointestinal manifestations.

PMID- 28509282
TI  - Successful management of bilateral emphysematous pyelonephritis with abscess
      formation in a chronic hemodialysis patient: a case report.
AB  - Bilateral emphysematous pyelonephritis (EPN) has seldom been reported in patients
      on maintenance hemodialysis (HD). Percutaneous catheter drainage (PCD) or
      nephrectomy is often required in the treatment of bilateral EPN because of its
      poor response to antimicrobial agents and high mortality rate. We report a
      patient with bilateral EPN on maintenance HD. An octogenarian man with diabetes
      mellitus who had previously undergone regular HD for 22 months was admitted to
      our hospital because of severe inflammation resulting from bilateral EPN. His
      lesions of EPN had resulted in abscess formation in both kidneys and right and
      left side retroperitoneal space. As patient refused interventional therapy
      including nephrectomy or PCD, he was treated conservatively. After treatment with
      several antimicrobial agents for 50 days, he completely recovered from bilateral
      EPN. To our knowledge, this is the first case report of successful conservative
      management (antimicrobial therapy alone) of bilateral EPN that developed in a
      chronic diabetic HD patient.

PMID- 28509283
TI  - In Vivo Molecular MRI of ICAM-1 Expression on Endothelium and Leukocytes from
      Subacute to Chronic Stages After Experimental Stroke.
AB  - Molecular MRI allows in vivo detection of vascular cell adhesion molecules
      expressed on inflamed endothelium, which enables detection of specific targets
      for anti-neuroinflammatory treatment. We explored to what extent MR contrast
      agent targeted to intercellular adhesion molecule-1 (ICAM-1) could detect
      endothelial- and leukocyte-associated ICAM-1 expression at different stages after
      experimental stroke. Furthermore, we assessed potential interfering effects of
      ICAM-1-targeted contrast agent on post-stroke lesion growth. Micron-sized
      particles of iron oxide (MPIO) functionalized with control IgG (IgG-MPIO) or anti
      ICAM-1 antibody (alphaICAM-1-MPIO) were administrated at 1, 2, 3, 7, and 21 days
      after unilateral transient middle cerebral artery occlusion in mice, followed by
      in vivo MRI and postmortem immunohistochemistry. alphaICAM-1-MPIO induced
      significant contrast effects in the lesion core on post-stroke days 1, 2, and 3,
      and in the lesion borderzone and contralesional tissue on post-stroke day 2.
      alphaICAM-1-MPIO were confined to ICAM-1-positive vessels and occasionally co
      localized with leukocytes. On post-stroke day 21, abundant leukocyte-associated
      alphaICAM-1-MPIO was immunohistochemically detected in the lesion core. However,
      MRI-based detection of alphaICAM-1-MPIO-labeled leukocytes was confounded by pre
      contrast MRI hypointensities, presumably caused by phagocytosed blood remains.
      IgG-MPIO did not induce significant MRI contrast effects at 1 h after injection.
      Lesion development was not affected by injection of alphaICAM-1-MPIO or IgG-MPIO.
      alphaICAM-1-MPIO are suitable for in vivo MRI of ICAM-1 expression on vascular
      endothelium and leukocytes at different stages after stroke. Development of
      clinically applicable MPIO may offer unique opportunities for MRI-based diagnosis
      of neuroinflammation and identification of anti-inflammatory targets in acute
      stroke patients.

PMID- 28509284
TI  - AP-VAS 2012 case report: a case of myeloperoxidase antineutrophil cytoplasmic
      antibody-positive microscopic polyangiitis with rapidly progressive
      glomerulonephritis and hearing loss.
AB  - A 74-year-old Japanese woman was admitted to our hospital because of fever,
      fatigue, and hearing loss associated with vertigo. She had a 1-year history of
      hearing impairment that got worse gradually and had been treated as otitis media
      with effusion, but without remarkable improvement. After admission, she developed
      renal dysfunction associated with hematuria and proteinuria. Laboratory tests
      showed leukocytosis and elevated C-reactive protein. Myeloperoxidase
      antineutrophil cytoplasmic antibody (MPO-ANCA) was elevated, but proteinase-3
      antineutrophil cytoplasmic antibody (PR3-ANCA) was negative. Renal biopsy
      revealed pauci-immune focal necrotizing glomerulonephritis with crescents. She
      was diagnosed as having MPO-ANCA-associated polyangiitis. After treatment with
      500 mg methylprednisolone applied intravenously for 3 days, followed by 40 mg
      prednisolone administered orally, renal function recovered completely. Her
      hearing also improved. Although otolaryngological symptoms are common in PR3-ANCA
      associated vasculitis, hearing loss is a rare manifestation of MPO-ANCA
      associated vasculitis (MPO-AAV). Our case suggests that AAV should be considered
      in the differential diagnosis of hearing loss.

PMID- 28509285
TI  - AP-VAS 2012 case report: a case of lupus nephritis with predominant synchronous
      cellular crescent formation and myeloperoxidase-antineutrophil cytoplasmic
      antibody seropositivity.
AB  - Several cases with an overlap of antineutrophil cytoplasmic antibody (ANCA)
      associated glomerulonephritis (GN) and lupus nephritis (LN) features have been
      reported in recent years. However, the clinical and the pathologic features of
      this condition, including mode of development, histology, and response to
      treatment, are not fully understood. We report a 77-year-old woman who was
      diagnosed with Sjogren syndrome 15 years previously. The patient presented with
      acute worsening of renal function and was diagnosed with new-onset systemic lupus
      erythematosus. A renal biopsy specimen revealed proliferative LN with synchronous
      cellular crescents. She was also seropositive for myeloperoxidase-ANCA. Together
      with the positive staining for immunoglobulins and complement factors on
      immunofluorescence microscopy and scant subendothelial deposits by electron
      microscopy, we reached a diagnosis of ANCA-associated crescentic GN overlapping
      with LN. Although immunosuppressive treatment with methylprednisolone pulse
      therapy and intravenous cyclophosphamide followed by oral predonisolone was
      initiated, along with intermittent hemodialysis, these treatments did not induce
      remission of her GN. Therefore, she continued regular intermittent hemodialysis.
      However, she died because of candida pneumonia 4 months after admission.
      Generally, the glomeruli of patients with ANCA-associated GN exhibit different
      stages of crescents, namely cellular, fibrocellular, or fibrous. The
      histologically synchronous crescents in this case indicate that ANCA-associated
      GN overlapping with LN can progress more rapidly than that without LN. This
      overlapping type of GN may be resistant to conventional immunosuppressive
      therapies.

PMID- 28509286
TI  - Mizoribine as a safe and effective combined maintenance therapy with prednisolone
      for anti-neutrophil cytoplasmic antibody-associated vasculitis in a hemodialysis
      patient.
AB  - A 77-year-old man developed severe renal insufficiency due to proteinase 3 anti
      neutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, and was started
      on hemodialysis (HD). Because his renal insufficiency appeared to be
      irreversible, he was maintained on oral prednisolone (PSL) at 5 mg/day. However,
      a disease flare-up with alveolar hemorrhage occurred. Serology revealed elevated
      levels of PR3-ANCA and C-reactive protein (CRP). The patient was given pulse
      therapy with a quarter dose of methylprednisolone (m-PSL) (250 mg, 3 days),
      followed by oral PSL at 15 mg/day. As a supplemental treatment, he was given 25
      mg of mizoribine (MZR) immediately after each HD session. Subsequently, the
      levels of PR3-ANCA and CRP decreased, and the alveolar hemorrhage resolved. The
      dose of MZR to be given was determined by measuring the patient's serum
      concentrations of MZR at various time points after the HD session. The
      maintenance dose of MZR was finally set at 50 mg. At present, the oral PSL dosage
      has been tapered to 10 mg/day, and the patient has achieved a state of remission
      without any side effects.

PMID- 28509287
TI  - Unusually indolent MPO-ANCA: associated vasculitis-report of two cases.
AB  - Vasculitis associated with antineutrophil cytoplasmic antibodies specific to
      myeloperoxidase generally presents as a life- and organ-threatening disease that
      evolves over several months. It is a syndrome in which prompt diagnosis and
      therapy are important both in terms of short-term survival and long-term organ
      damage. Two cases with quite a different course, sustained and indolent with
      limited progression over many years, are described in this report. They are
      compared to cases in the literature. Indolent cases of granulomatous polyangiitis
      associated with antineutrophil cytoplasmic antibodies against proteinase-3 are
      well recognised, but these two cases of microscopic polyangiitis are almost
      unique.

PMID- 28509288
TI  - Severe hyponatremia caused by secondary adrenal insufficiency in a patient with
      giant pituitary prolactinoma.
AB  - A 55-year-old-man was admitted to Saiseikai Central Hospital, Tokyo, Japan,
      complaining of nausea and appetite loss, and was found to have severe
      hyponatremia. Despite severe hyponatremia and plasma hypo-osmolarity, urinary
      sodium excretion was not reduced. A brain magnetic resonance imaging (MRI) scan
      revealed a giant pituitary prolactinoma, and endocrinological tests showed a
      markedly increased prolactin level. Despite the observation that the basal plasma
      ACTH level was normal, serum cortisol and urinary cortisol excretion levels were
      low. Rapid ACTH loading sufficiently stimulated an increase in serum cortisol
      levels, suggesting secondary adrenal insufficiency. Notably, loading of CRH
      induced a good ACTH response; however, the serum cortisol response remained low.
      In contrast, the continuous daily administration of exogenous ACTH dramatically
      increased serum cortisol levels. These discrepant responses may have been caused
      by the low biological activity of innate ACTH. Following partial resection of the
      prolactinoma, postoperative adjuvant therapy with cabergoline effectively reduced
      prolactin levels, but did not improve the hyponatremia. In contrast,
      hydrocortisone replacement therapy recovered the serum sodium level to the normal
      range. The present case is the first report describing a link between severe
      hyponatremia and biologically inactive circulating ACTH as a likely result of
      giant prolactinoma.

PMID- 28509289
TI  - AP-VAS 2012 case report: a case of systemic MPO-ANCA-associated vasculitis that
      demonstrated brain infarction and immunohistochemically MPO-positive capillaries.
AB  - We present a case of an aged male with myeloperoxidase anti-neutrophil
      cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis with onset of brain
      infarction that demonstrated immunohistochemically MPO-positive capillaries at
      autopsy. The patient initially presented with gait difficulty and right-sided
      weakness. Since an imaging study revealed brain infarction, he was admitted to
      our hospital and medicated by antiplatelet agents. Continuous fever and elevated
      serum C-reactive protein (CRP), hematuria of glomerular origin, renal
      dysfunction, and high serum titer of MPO-ANCA were detected. Systemic toxicoderma
      appeared, and skin biopsy revealed small-vessel vasculitis; thus, he was
      diagnosed with MPO-ANCA-associated vasculitis. Steroid therapy
      (methylprednisolone 30 mg/day) was started, and general status improved. However,
      he died of shock 6 days after the start of the therapy. Autopsy revealed massive
      retroperitoneal hemorrhage with necrotizing small-vessel vasculitis in systemic
      organs including retroperitoneum, skin, brain, testes, and kidneys.
      Immunohistochemically, infiltration of MPO-positive white blood cells into the
      capillaries was occasionally observed, along with the features of MPO-positive
      capillaries. Cerebrovascular involvement of MPO-ANCA-associated vasculitis is
      rare compared with renal and pulmonary manifestations, having been reported to
      occur in up to 4 % of patients. Furthermore, as we have recently reported, MPO
      immunopositive capillaries may appear only during the hyperacute stage of the
      disease. Therefore, the present case represents the unique combination of these
      two rare manifestations.

PMID- 28509290
TI  - A case of infantile systemic lupus erythematosus with severe lupus nephritis and
      EBV infection.
AB  - Infantile systemic lupus erythematosus (iSLE) is extremely rare. Patients with
      iSLE usually become severely unwell and have poor prognosis. Epstein-Barr virus
      (EBV) infection has been implicated in the development of SLE in both adults and
      children. Recently, we experienced a case of iSLE with severe lupus nephritis
      (LN) and EBV infection. A 14-month-old Japanese boy was diagnosed with iSLE
      according to the American Rheumatism Association criteria. Renal biopsy showed LN
      classified as International Society of Nephrology/Renal Pathology Society class
      IV-G (A), and liver biopsy showed lupus hepatitis. Steroid pulse treatment
      resulted in improvement of the levels of serological markers of SLE such as
      double-stranded DNA and complement, but his proteinuria worsened and he developed
      acute nephritic-nephrotic syndrome. Monthly intravenous cyclophosphamide (IVCY)
      therapy dramatically reduced his proteinuria and led to complete remission
      (urinary protein/creatinine ratio <0.1 mg/mg), with gradual improvement in levels
      of serological markers. EBV antibody titers and EBV polymerase chain reaction
      (PCR) of peripheral blood lymphocytes suggested that the onset of iSLE might have
      been associated with EBV infection. At his 2-year follow-up visit, he was healthy
      and remained in complete remission. We conclude that IVCY treatment might be well
      tolerated and effective in cases of iSLE. EBV infection might play an important
      role in the pathogenesis of iSLE.

PMID- 28509291
TI  - Nephrotic-range proteinuria in an infant with thin basement membrane nephropathy.
AB  - Thin basement membrane nephropathy (TBMN) with heterozygous COL4A3/COL4A4
      mutations is considered to be a cause of benign familial hematuria. The disease
      has been believed to have excellent prognosis and TBMN in early childhood is
      rarely associated with nephrotic-range proteinuria. Furthermore, the presence of
      proteinuria in patients with TBMN is associated with autosomal-dominant Alport
      syndrome, which has poorer prognosis in later life. We present an infant case of
      nephrotic-range proteinuria associated with TBMN caused by heterozygous COL4A4
      mutation. A previously healthy 3-year-old boy developed microhematuria and
      nephrotic-range proteinuria. Renal pathology simply revealed thinning of the
      glomerular basement membrane (GBM) and mutational analysis revealed a novel
      heterozygous mutation in COL4A4. He was treated with lisinopril for 1.5 years,
      which resolved his proteinuria and hematuria. At the most recent follow-up at 6.5
      years of age, urinalysis and kidney function were completely normal, without
      requiring medication. However, transient but repeated moderate to nephrotic-range
      proteinuria and microscopic hematuria occurred in association with other
      illnesses. This case highlights the spectrum of phenotypes that may be apparent
      in an infant with TBMN. Thinning of the GBM can cause transient nephrotic-range
      proteinuria, particularly in the early stages of TBMN.

PMID- 28509292
TI  - Granulomatosis with polyangiitis associated with IgA nephropathy.
AB  - Granulomatosis with polyangiitis (GPA), previously referred to as Wegener's
      granulomatosis, is a rare necrotizing granulomatous vasculitis, especially in
      children. GPA affects small- to medium-sized vessels, leading to involvement of
      multiple organs, including the upper and lower respiratory tracts and kidneys.
      Glomerular lesions associated with GPA typically present as crescentic
      glomerulonephritis with necrotizing lesions, with little or no staining for
      immunoglobulins and complement proteins. We report a unique pediatric case of GPA
      associated with IgA nephropathy, a representative immune-mediated glomerular
      disease. The initial renal biopsy specimen revealed fibrous sclerosis and mild
      mesangial proliferation without deposition of IgA. However, after clinical
      remission of GPA by treatment, the serum IgA level continued to be significantly
      higher than normal, and her paranasal sinusitis was poorly controlled. An acute
      upper respiratory infection resulted in worsened urinary findings without any
      systemic signs of GPA. The second renal biopsy specimen revealed deposition of
      IgA and C3 in the mesangium. The patient was treated with oral prednisolone
      alone, which led to complete remission of proteinuria within 1 month. IgA
      nephropathy is possibly associated with GPA during remission stage, and serum IgA
      level may be a valuable indicator to predict its association.

PMID- 28509293
TI  - Proliferative glomerulonephritis with monoclonal IgG2kappa deposit successfully
      treated with steroids: a case report and review of the literature.
AB  - A novel form of glomerular injury with monoclonal immunoglobulin (Ig) IgG
      deposition, termed "proliferative glomerulonephritis (GN) with monoclonal IgG
      deposits" (PGNMID), is a recently described entity. PGNMID presents with various
      histological patterns, such as membranoproliferative GN, endocapillary
      proliferative GN and membranous nephropathy (MN). The deposits are composed of
      monoclonal immunoglobulin, most commonly IgG3 and occasionally IgG2. At present,
      the clinical significance of each IgG subclass and the morphological patterns of
      glomerular injury have not been fully investigated due to the limited number of
      PGNMID cases reported. The patient was a 27-year-old woman presenting with a mild
      degree of proteinuria and no other physical or serological abnormalities.
      Monoclonal Ig could not be identified in her serum or urine. Renal biopsy found
      features of MN with deposition of monoclonal IgG2kappa. Electron microscopy
      examination revealed non-organised electron-dense deposits predominantly in
      subepithelial locations. Based on a diagnosis of PGNMID, she was treated with
      prednisolone and proteinuria significantly decreased in less than 4 weeks.
      Although the clinical outcomes of PGNMID remain to be defined, MN features may
      possibly be a sign of favourable prognosis-a hypothesis supported by recent
      reports. The absence of advanced chronic damage in the kidney, such as
      glomerulosclerosis or tubulointerstitial fibrosis, may also have contributed to
      the favourable outcome in the present case. Further studies on additional PGNMID
      cases that allow the correlation of morphological features and IgG subclasses
      with clinical outcomes are needed in order to confirm our findings and further
      solidify the clinical aspects of this new disease entity.

PMID- 28509294
TI  - Proliferative glomerulonephritis with monoclonal IgM-kappa deposits in chronic
      lymphocytic leukemia/small lymphocytic leukemia: case report and review of the
      literature.
AB  - A 48-year-old man with chronic lymphocytic leukemia presented with nephrotic
      syndrome, hematuria, and mild deterioration of renal function. Further analysis
      using serum immunofixation electrophoresis detected monoclonal immunoglobulin
      (Ig) M-kappa and IgG-kappa M-protein. Testing for cryoglobulin in serum was
      negative. Light microscopy of a renal biopsy specimen showed
      membranoproliferative glomerulonephritis features with marked mononuclear cell
      infiltration in the interstitium. On immunofluorescence study, the deposition of
      IgM heavy chain was predominantly observed with the same distribution of kappa
      light chain, whereas no lambda light chain was found. Electron microscopy
      revealed fine granular deposits in the mesangial, subendothelial, and
      subepithelial areas, mimicking those observed in the immune complex-mediated
      glomerulonephritis. These pathological findings were consistent with recently
      described cases of proliferative glomerulonephritis with monoclonal IgG deposits.
      Thus, monoclonal IgM deposition can also cause proliferative glomerulonephritis.

PMID- 28509295
TI  - Antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis with
      membranous nephropathy treated using thiamazole.
AB  - A 21-year-old woman with nephrotic syndrome was referred to our hospital. She had
      congenital diaphragmatic hernia, hypoxic ischemic encephalopathy, and mental
      retardation, and had been treated for hyperthyroidism with thiamazole in another
      hospital. Serum creatinine was 37.8 MUmol/L and antineutrophil cytoplasmic
      antibody against myeloperoxidase (MPO-ANCA) was 39 EU. Urinalyses were 3+ for
      proteins and 3+ for occult blood. A renal biopsy was performed. An examination
      using light microscopy (LM) revealed necrotizing glomerulonephritis with crescent
      formation. Immunofluorescence microscopy showed granular staining with
      immunoglobulin G and complement component 3 along the capillary walls. Electron
      microscopy (EM) disclosed subepithelial dense deposits. A renal biopsy suggested
      necrotizing glomerulonephritis with membranous nephropathy (MN) in stages I or
      II. Since many cases of drug-induced ANCA-associated glomerulonephritis (AAG)
      have been reported, we stopped thiamazole and treated with corticosteroid. The
      MPO-ANCA titer became negative 49 days after the initiation of treatment. Two
      years after the first treatment, the MPO-ANCA titer became elevated again and was
      82 EU. The patient was administered cyclophosphamide and prednisone. However, the
      MPO-ANCA titer did not decrease. A renal biopsy was performed again 3 years after
      the first renal biopsy. LM revealed no crescentic formation but demonstrated
      spike formations along the glomerular basement membrane. EM also disclosed
      subepithelial dense deposits, but less than the first biopsy. The renal biopsy
      suggested MN in stages II or III. AAG was regarded as inactive after
      corticosteroid treatment. Therefore, ciclosporin administration was started. In
      conclusion, we experienced a rare case of AAG complicated with MN. The
      histopathologic results showed that immunosuppressive therapy seemed to be
      effective in treating crescentic glomerulonephritis; furthermore, it reduced
      proteinuria but could not reduce the MPO-ANCA titer.

PMID- 28509296
TI  - Renal biopsy cases in myeloproliferative neoplasms (MPN).
AB  - We performed renal biopsy in three cases complicated by myeloproliferative
      neoplasms (MPN). Although several cases of glomerulonephritis associated with MPN
      have been reported, the etiologies of the renal disorders were not established
      (Plomley et al., Aust NZ J Med, 13:125-129, 1983; Sharma et al., Nephron, 69:361,
      1995; Kanauchi et al., Intern Med, 33:36-40, 1994; Kasuno et al., Nephrol Dial
      Transplant, 12:212-215, 1997; Au et al., Am J Kid Dis, 34:889-893, 1999; Kosch et
      al., Nephrol Dial Transplant, 15:1710-1711, 2000; Oymak et al., Nephron, 86:346
      347, 2000; Chun et al., Am J Nephrol, 20:344-346, 2000; Chung et al., Am J
      Nephrol, 22:397-401, 2002; Asaba et al., Clin Exp Nephrol, 7:296-300, 2003;
      Haraguchi et al., Clin Exp Nephrol, 10:74-77, 2006; Saigusa et al., J Nephrol,
      19:656-658, 2006; Okuyama et al., Clin Nephrol, 6:412-415, 2007; Nishi et al.,
      Clin Nephrol, 5:393-398, 2010; Ulusoy et al., Intern Med, 49:2477, 2010). A
      review of previous reports of renal biopsy cases with MPN in the English
      literature suggested that circulation control is important for the treatment of
      renal disorders that mimic glomerulonephritis in MPN.

PMID- 28509297
TI  - AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic
      glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of
      the lung.
AB  - A 76-year-old man with lung cancer and multiple metastases was admitted for
      purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma
      of the lung had been diagnosed 6 months earlier. Two anti-cancer drug regimens
      had no effect. At admission, his survival with his malignancy was estimated to be
      several months. Renal biopsy revealed pauci-immune necrotizing crescentic
      glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase
      anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme
      linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by
      indirect immunofluorescence. He was diagnosed with ANCA-negative pauci-immune
      CrGN. Although steroids were initiated, the patient died of renal failure and
      intestinal bleeding 2 weeks later. It was later found that cancer cells were
      positive for interleukin (IL)-6 and that serum IL-6 levels were significantly
      elevated, concomitantly with increased IL-8, granulocyte-colony stimulating
      factor and transforming growth factor-beta levels. Some kinds of lung cancer are
      known to produce IL-6 that activate neutrophils and are related to ANCA
      associated CrGN. It appears that IL-6 can activate neutrophils in the
      pathogenesis of ANCA-negative pauci-immune CrGN with lung cancer. Therapy that
      blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms
      in such cases.

PMID- 28509298
TI  - A rare case: childhood-onset C3 glomerulonephritis due to homozygous factor H
      deficiency.
AB  - C3 glomerulopathy is a recently described pathological entity including dense
      deposit disease and C3 glomerulonephritis (C3GN). In some cases, C3
      glomerulopathy is associated with defects or even complete deficiency of factor
      H. However, complete factor H deficiency among patients with C3GN is rare, and
      paediatric cases have not yet been described. Here, we report a child with
      homozygous factor H deficiency who presented with haematuria and minor
      proteinuria, together with undetectable plasma C3 levels, at the age of 10 years.
      Kidney biopsy demonstrated C3GN. Detailed complement analysis revealed complete
      factor H deficiency due to a homozygous CFH mutation. Furthermore, there was a
      complete deletion of CFHR-1/-3. During follow-up, the patient has had recurrent
      episodes of macro-haematuria and minor proteinuria, but during 4 years of follow
      up, no deterioration of renal function has been observed. Mutations of factor H
      in C3GN have been described; however, complete CFH deficiency is rare in these
      patients. Furthermore, clinical presentation usually occurs in adulthood.
      Therefore, this case presents a rare manifestation of the disease and might
      contribute to the early detection of similar cases also in childhood.

PMID- 28509299
TI  - Development of minimal-change glomerular disease and Hashimoto's thyroiditis
      during the treatment of sarcoidosis.
AB  - Minimal-change glomerular disease, sarcoidosis and autoimmune thyroid disease
      rarely occur in the same patient. We herein report a patient in which minimal
      change glomerular disease and Hashimoto's thyroiditis developed during the
      treatment of sarcoidosis with steroids. A 66-year-old female was admitted to our
      hospital with symptoms of nephrotic syndrome. Nine months before admission, she
      was diagnosed as having ocular and pulmonary sarcoidosis, for which prednisolone
      at an initial dose of 40 mg/day was started. When the dose of prednisolone was
      tapered to 20 mg/day, she noticed swelling of the lower extremities. Examination
      confirmed the simultaneous occurrence of minimal-change glomerular disease and
      Hashimoto's thyroiditis, which were diagnosed based on kidney histology,
      ultrasonography of the thyroid gland and positive antithyroglobulin antibodies.
      We used intravenous methylprednisolone pulse therapy followed by 40 mg/day oral
      prednisolone. The patient achieved complete remission of nephrotic syndrome and
      steroids were tapered without relapse.

PMID- 28509300
TI  - Pulmonary and gastric metastatic calcification due to milk-alkali syndrome: a
      case report.
AB  - The incidence of metastatic calcification is influenced by high serum calcium and
      phosphate concentrations and local physicochemical conditions, such as pH. A high
      pH accelerates tissue calcification. Patients with milk-alkali syndrome typically
      present with renal failure, hypercalcemia, and metabolic alkalosis, which are
      caused by the ingestion of calcium and absorbable alkali. Among patients with
      impairment of renal function, milk-alkali syndrome is a major cause of
      hypercalcemia. Long-term use of furosemide will lead to hypokalemia, metabolic
      alkalosis, and eventually renal failure (i.e., pseudo-Bartter syndrome). Even if
      the level of calcium ingestion is relatively low, the renal failure caused by
      long-term furosemide use can readily lead to milk-alkali syndrome. We describe a
      case of a 45-year-old woman who was admitted with cough and dyspnea and presented
      with pulmonary and gastric metastatic calcification. She had been taking
      alfacalcidol and oral alkaline medications such as sodium bicarbonate and calcium
      carbonate as well as oral furosemide for a long time. The patient was found to
      have hypercalcemia, chronic renal failure, and metabolic alkalosis, so milk
      alkali syndrome was diagnosed. Saline was administered and oral medications were
      discontinued. Serum creatinine levels subsequently decreased, but pulmonary
      metastatic calcification was not diminished. In this case, the milk-alkali
      syndrome that caused the severe metastatic calcification was exacerbated by
      multiple factors, including oral alkaline medications such as sodium bicarbonate
      and calcium carbonate. In addition, metabolic alkalosis and renal failure were
      affected by long-term furosemide use (i.e., pseudo-Bartter syndrome).

PMID- 28509301
TI  - AP-VAS 2012 case report: anti-glomerular basement membrane disease with high
      titer of myeloperoxidase anti-neutrophil cytoplasmic antibody-an autopsy case
      report.
AB  - It has been reported that patients who are positive for both myeloperoxidase anti
      neutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane
      (GBM) antibody have a poor prognosis. We present an autopsy case of anti-GBM
      disease with a high titer of MPO-ANCA. The patient was a 77-year-old woman with a
      medical history of idiopathic interstitial pneumonia. After being treated for
      bacterial pneumonia, she was referred to our hospital for evaluation of non
      nephrotic range proteinuria, hematuria, and a course of rapidly progressive
      glomerulonephritis. Results of urinalysis were 2+ for protein and 3+ for blood,
      with many dysmorphic red blood cells observed in the urinary sediment. A sample
      of a 24-h urine collection contained 0.3 g protein. The serum creatinine
      concentration was 5.0 mg/dl on admission. The patient tested positive for MPO
      ANCA at a titer of >640 EU and for anti-GBM antibody at a titer of 14 EU. Renal
      biopsy revealed glomerulonephritis with crescent formation, and
      immunofluorescence studies showed that the glomeruli had a generalized linear
      fluorescence and anti-immunoglobulin G (IgG) and C3 along the peripheral
      glomerular capillaries. She was diagnosed with anti-GBM disease. Treatment was
      started with intravenous prednisolone and oral cyclophosphamide, followed by
      plasma exchange. Despite improved renal function, she died of pulmonary
      hemorrhage. Autopsy revealed deposits of IgG and C3 in the basement membranes of
      lung alveoli.

PMID- 28509303
TI  - A novel mutation in the uromodulin gene in a Japanese family with a mild
      phenotype of familial juvenile hyperuricemic nephropathy.
AB  - Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal-dominant
      disorder that is characterized by hyperuricemia and chronic renal failure and
      results in end-stage renal failure. FJHN is caused by mutations in the UMOD gene,
      which encodes uromodulin. Uromodulin contains three epidermal growth factor (EGF)
      like domains, a domain of eight cysteine residues (D8C), and a zona pellucid-like
      domain. Over 90 % of UMOD mutations are missense mutations, and over 80 % exist
      in exon 4, which encodes both D8C and the EGF-like domains. A 56-year-old woman
      was diagnosed with hyperuricemia with a serum uric acid level of 7.5 mg/dL, and
      stage III chronic kidney disease (CKD) with a serum creatinine level of 1.12
      mg/dL and an estimated glomerular filtration rate of 39.9 mL/(min 1.73 m2). The
      patient had a family history of hyperuricemia and stage IV CKD; both the patient
      and her affected family members had a novel mutation in the UMOD gene: c.C518G
      (p.P173R), located between the EGF-like domains and D8C. This mutation, along
      with previously reported nearby mutations, causes a clinically mild phenotype of
      FJHN. It is important that physicians consider the diagnosis of FJHN in patients
      with a family history of hyperuricemia associated with renal dysfunction, even if
      the patient has only mild renal impairment.

PMID- 28509302
TI  - A case of disseminated tuberculosis after the initiation of hemodialysis.
AB  - A 67-year-old man with diabetes mellitus, chronic kidney disease, chronic heart
      failure, and amputation of the left lower limb was admitted to our hospital with
      decreasing renal function. On admission, he was started on hemodialysis. He
      simultaneously developed a urinary tract infection, infected necrotic wound of
      the right lower limb, and pneumonia, and was treated with broad-spectrum
      antibiotics. Although his general condition improved, fever and anorexia
      persisted and jaundice worsened. He died 138 days after admission. Autopsy
      revealed granulomas in the lungs, liver, and spleen. Cultures revealed
      Mycobacterium tuberculosis, leading to the diagnosis of disseminated
      tuberculosis.

PMID- 28509305
TI  - AP-VAS 2012 case report: two patients with rheumatoid arthritis suspected of
      relapsed microscopic polyangiitis after initiation of dialysis.
AB  - We report two patients with rheumatoid arthritis (RA) who were suspected of
      microscopic polyangiitis during maintenance dialysis. Case 1 was a 52-year-old
      woman with RA diagnosed at the age of 38 years and treated successfully with gold
      compounds. At the age of 43 years, she presented with progressive renal
      dysfunction and abnormal urine sediments, and a renal biopsy revealed crescentic
      nephritis with advanced glomerular sclerosis. Myeloperoxidase antineutrophil
      cytoplasmic antibody (MPO-ANCA) was not measured on that occasion. She reached
      end-stage renal failure within 4 months and started peritoneal dialysis. Eight
      years later, soon after she was switched to hemodialysis, she developed fever of
      unknown origin. MPO-ANCA was elevated to 37 EU, although there were no other
      signs or symptoms suggestive of vasculitis. After taking prednisolone orally (10
      mg/day), her fever withdrew, and MPO-ANCA became undetectable. Case 2 was a 71
      year-old woman with RA diagnosed at the age of 60 years and treated with gold
      compounds. She developed renal failure of unknown cause (no biopsy was
      performed), and started hemodialysis at the age of 69 years. One year later, she
      presented with fever and subsequently developed cough with hemoptysis. MPO-ANCA
      was elevated to 62 EU. Treatment with azathioprine 50 mg and prednisolone 35 mg
      daily brought remarkable clinical improvement, and MPO-ANCA became undetectable.
      These cases highlight the importance of measuring ANCA even in RA patients on
      dialysis who present with fever of unknown origin or with underlying kidney
      disease of uncertain etiology.

PMID- 28509304
TI  - A case of anti-GBM glomerulonephritis superimposed on HBV-associated membranous
      nephropathy.
AB  - In September 2010, a 75-year-old hepatitis B virus (HBV)-positive man was
      admitted to our hospital because of fever, persistent cough, general fatigue, and
      leg edema. The patient was a hepatitis B surface antigen carrier with detectable
      HBV DNA level. On admission, laboratory examination revealed severe inflammatory
      signs, decreased serum albumin, and renal insufficiency with proteinuria. The
      patient had rapidly progressive renal insufficiency without pulmonary involvement
      over the few days after admission. Renal biopsy showed membranous nephropathy
      (MN) with crescent formation. Further serological study revealed a high titer of
      anti-glomerular basement membrane (GBM) antibody, suggestive of anti-GBM
      glomerulonephritis superimposed on HBV-associated MN. For both preventing HBV
      reactivation during immunosuppressive therapy and treating HBV-associated MN, the
      administration of entecavir was immediately initiated, and then treatment with
      plasma exchange (PE) and intravenous methylprednisolone administration was
      performed. Both HBV DNA level and an anti-GBM titer became undetectable, and
      clinical remission of MN was subsequently achieved. This was a rare case of an
      elderly patient with anti-GBM glomerulonephritis superimposed on HBV-associated
      MN, who was successfully treated with PE, corticosteroid, and entecavir
      combination therapy.

PMID- 28509308
TI  - List of referees.

PMID- 28509306
TI  - AP-VAS 2012 case report: a case of ANCA-negative crescentic glomerulonephritis
      complicating multiple opportunistic infections in the digestive tract.
AB  - Crescentic glomerulonephritis (GN) is one of the common causes of rapidly
      progressive glomerulonephritis (RPGN). Pauci-immune crescentic GN is usually
      associated with anti-neutrophil cytoplasmic antibody (ANCA). However, patients
      with pauci-immune crescentic GN who lack ANCAs have recently been reported.
      Approximately 10-30 % of patients with pauci-immune crescentic GN lack ANCAs. The
      clinical characteristics of patients with ANCA-negative pauci-immune crescentic
      GN are not entirely the same as patients with ANCA-positive GN, and this suggests
      that ANCA-negative and ANCA-positive pauci-immune crescentic GN might be
      different disease entities. We report a patient with ANCA-negative crescentic GN
      complicated with multiple opportunistic infections (Candida albicans, herpes
      simplex virus, and Cytomegalovirus) in the digestive tract during the course of
      immunosuppressive therapy. After antifungal and antiviral therapies including
      itraconazole, valaciclovir, and ganciclovir, she recovered from multiple
      opportunistic infections. The occurrence of comorbid opportunistic infections
      during the course of immunosuppressive therapy may not be rare in the elderly.
      However, a case of multiple opportunistic infections limited to the digestive
      tract is very rare.

PMID- 28509307
TI  - AP-VAS 2012 case report: MPO-ANCA-negative relapse of MPO-ANCA-associated
      vasculitis.
AB  - A 79-year-old female was admitted to our hospital with fever, proteinuria,
      hematuria, high levels of C-reactive protein (CRP), and high titer of
      myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA). Our diagnosis was
      microscopic polyangiitis (MPA) and she was treated with steroid pulse therapy.
      Clinical remission was induced; however, the disease relapsed with saddle nose
      and necrotizing vasculitis of the nasal cavity mucosa 1 year later. Although
      there was no elevation of the MPO-ANCA titer, we diagnosed the patient with
      relapse of MPO-ANCA-positive granulomatosis with polyangiitis (GPA). Remission
      was induced again with steroids and azathioprine. It has been reported that the
      number of MPO-ANCA-positive patients in Asian countries is relatively higher than
      in Western countries. We checked 29 GPA patients in our hospital and 9 patients
      (31.0 %) were MPO-ANCA-positive. In addition, it is not rare that an ANCA
      associated vasculitis (AAV) patient who has been in remission with negative ANCA
      relapses without any elevation of ANCA titer. We checked the transition of ANCA
      titer of 24 AAV patients in our hospital who relapsed and 6 patients (25 %)
      relapsed without any elevation of ANCA titer. We should be careful for a relapse,
      even if the ANCA titer remains negative. It is also possible that ANCA had been
      changed so as not to be detected by the same enzyme-linked immunosorbent assay
      (ELISA) kit. Thus, it is also important to change the detection system if
      clinical symptoms are worsened while ANCA is still negative.

PMID- 28509309
TI  - Epidemiological profile and antibiotic resistance of Pseudomonas aeruginosa
      isolates in burn and Traumatology center in Tunisia over a three-year period.
AB  - BACKGROUND: Pseudomonas aeruginosa is a known opportunistic pathogen frequently
      causing serious infections in burned patients. AIM: To analyze the
      epidemiological profile of Pseudomonas aeruginosa isolated in a Tunisian burn
      unit. METHODS: During a 3-year period (from 01 July 2008 to 30 June 2011), 544
      non repetitive strains of P. aeruginosa were isolated from burn patients.
      Susceptibility to antibiotics was assessed according to CA-SFM guidelines.
      Serotypes were identified by slide agglutination test using P.aeruginosa O
      antisera (Biorad). Producing carbapenemase was analyzed for 202 imipenem
      resistant isolates by EDTAtest. Susceptibility testing data were stored in a
      laboratory data base using whonet 5.3 software. RESULTS: The most frequent sites
      of isolation were cutaneous infections and blood cultures (83.4%). The
      percentages of resistant isolates were as follows: ceftazidime: 34%; imipenem:
      37.1%, ciprofloxacin: 27.1% and amikacin: 29.6%. The most prevalent serotypes
      were: 011(51%), 06(17%), 03 (8%), 04(12%), 012(5%). Among the 202 imipenem
      resistant strains, 58% expressed a metallocarbapenemase. All theses strains were
      resistant to all tested antibiotics except colistin and belonged to the serotype
      O11. CONCLUSION: The dissemination of carbapenemases strains must be contained by
      implementation of timely identification, strict isolation methods and better
      hygienic procedures.

PMID- 28509310
TI  - Circulating tumor cells in different stages of colorectal cancer.
AB  - INTRODUCTION: Liquid biopsies are noninvasive tests using blood or body fluids to
      detect circulating tumor cells (CTCs) or the products of tumor cells, such as
      fragments of nucleic acids or proteins that are shed into biological fluids from
      primary tumor or its metastates. The analysis of published clinical studies
      provides coherent evidence that the presence of CTCs detected in peripheral blood
      is a strong prognostic factor in patients with colorectal carcinoma (CRC). The
      aim of the study was to implement size-based separation protocol of CTCs in CRC
      patients. MATERIAL AND METHODS: Patients diagnosed with different stages of CRC
      (n = 98) were included in the study. All patients have been diagnosed for
      colorectal adenocarcinoma by pathology examination, 45 patients with colon
      carcinoma and 53 with rectosigmoid cancer. A size-based separation method
      (MetaCell(r)) for viable CTC enrichment from peripheral blood was used to assess
      the presence of CTCs by cytomorphological evaluation using vital fluorescence
      microscopy. RESULTS: Cytomorphological analysis revealed that 81 (83%) tested
      samples were CTC-positive and 17 (17%) were CTC-negative. We report a successful
      isolation of CTCs with proliferation potential in patients with CRC. The CTCs
      were cultured in vitro for further downstream applications. Some of the isolated
      CTCs were able to grow in vitro for 6 months as a standard cell culture.
      CONCLUSIONS: We established a reliable, inexpensive and relatively fast protocol
      for CTCs enrichment in CRC patients by means of vital fluorescence staining which
      enables their further analysis in vitro.

PMID- 28509311
TI  - Ultrastructural characteristics of myenteric plexus in patients with colorectal
      cancer.
AB  - INTRODUCTION: It have been found previously that colorectal cancer (CRC) is
      accompanied by atrophy of myenteric plexuses (MPs) localized close to the tumor.
      The aim of the study was to compare ultrastructure of MPs localized in the
      unchanged part of the colon wall distant to CRC tumor with the ultrastructure of
      MPs in the vicinity of CRC tumor. MATERIAL AND METHODS: The present study was
      conducted using post-operative material derived from 11 patients with CRC.
      Samples of colon wall were taken from the margin of cancer invasion and from a
      macroscopically unchanged segment of the large intestine, immediately fixed and
      processed according to the standard protocol for transmission electron microscopy
      studies. RESULTS: In the MPs localized in the control part of colon wall the
      presence of numerous unmyelinated axons and cell bodies of neurons, interstitial
      cells of Cajal and enteroglial cells were observed. As compared to control
      samples, in the MPs located close to the tumor invasion, expansion of the
      extracellular matrix and myelin-like structures accompanying some nerve fibers
      were found. The appearance of mast and plasma cells was observed within MPs in
      the vicinity of CRC tumor. Sporadically, apoptotic cells were present inside the
      MPs. CONCLUSIONS: The presence of myelin-like structures and apoptotic cells
      within MPs located close to tumor invasion suggests that atrophy of MPs may be
      caused by factors released from CRC tumor.

PMID- 28509312
TI  - Histological, immunohistochemical and ultrastructural study of secondary
      compressed spinal cord injury in a rat model.
AB  - INTRODUCTION: Spinal cord injury (SCI) is a life-disrupting condition in which
      the first few days are the most critical. Secondary conditions remain the main
      causes of death for people with SCI. The response of different cell types to SCI
      and their role at different times in the progression of secondary degeneration
      are not well understood. The aim of this study was to study the histopathological
      changes of compressed spinal cord injury (CSCI) in a rat model. MATERIAL AND
      METHODS: Forty adult male Sprague-Dawley rats were divided into four groups. In
      group I, the rats were left without any surgical intervention (control). In group
      II, the rats were subjected to laminectomy without spinal cord compression (sham
      operated). In group III, the rats were sacrificed one day after CSCI. In group
      IV, the rats were sacrificed seven days after CSCI. The light microscopy was
      employed to study the morphology using H&E, osmic acid staining and
      immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The
      electron microscopy was applied for ultrastructure study. RESULTS:
      Histopathological examination of the posterior funiculus of the white matter
      revealed minute hemorrhages and localized necrotic areas on day 1, which
      transformed to areas of cavitation and fibrinoid necrosis surrounded by a
      demarcating rim of numerous astrocytes by day 7. The mean percentage of area of
      GFAP expression increased significantly by day 7. Osmic acid staining revealed
      swollen nerve fibers after one day, while numerous fibers had been lost by day 7.
      An ultrastructure study revealed swollen redundant thinned myelin and myelin
      splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the
      myelin sheath were folded and wrinkled with partial or complete demyelination
      areas. The myelin lamellae were disorganized and loose. The G-ratio was
      significantly greater on day 1 than day 7 after CSCI. CONCLUSIONS: In the rat
      model of CSCI details of the progressive spinal cord injury can be analyzed by
      morphological methods and may be helpful in the identification of the onset and
      type of clinical intervention.

PMID- 28509313
TI  - Decreased expression of survivin 2B in human pituitary adenomas. A preliminary
      study.
AB  - INTRODUCTION: We aimed to investigate survivin and its splice variants DEx3 and
      2B expressions in pituitary adenomas and normal pituitary glands using
      immunohistochemistry. MATERIAL AND METHODS: The study group consisted of eight
      pituitary adenomas: five of non-functional tumors, two of GH-secreting tumors,
      and one PRL-secreting tumor. Eight healthy pituitary tissue samples obtained
      after autopsy served as controls. RESULTS: Survivin expression was found in 87.5%
      of the study group and 100% of the controls. A positive staining of survivin 2B
      was found in 62.5% of pituitary adenomas and 100% of controls. Survivin DEx3 was
      recognized in 25% of pituitary adenomas and 12.5% of normal pituitary glands.
      There was significantly lower immunoreactivity of survivin 2B in pituitary
      adenomas when compared with normal pituitary glands (p = 0.0498). CONCLUSIONS:
      Survivin and its splice variants might be involved to some extent in benign tumor
      growth of pituitary adenomas. However, survivin cannot be regarded as a candidate
      for targeted therapy or molecular biomarker of pituitary adenomas.

PMID- 28509314
TI  - Influence of oxygen concentration on T cell proliferation and susceptibility to
      apoptosis in healthy men and women.
AB  - INTRODUCTION: Much of what we know about the functioning of human T lymphocytes
      is based on the experiments carried out in atmospheric oxygen (O2)
      concentrations, which are significantly higher than those maintained in blood.
      Interestingly, the gender differences in the activity of T cells and their
      susceptibility to apoptosis under different O2 conditions have not yet been
      described. The aim of the study was to compare two main markers of lymphocyte
      function: proliferation capacity and ability to produce cytokines as well as
      their susceptibility to apoptosis under two different O2 concentrations, between
      men and women. MATERIALS AND METHODS: 25 healthy volunteers, both males (13) and
      females (12) were recruited to the study (mean age 25.48 +/- 5.51). By using
      cytometry proliferation parameters of human CD4+ CD28+ cells or CD8+CD28+ cells
      in response to polyclonal stimulation of the TCR/CD3 complex at atmospheric (21%)
      and physiological (10%) O2 concentrations using our modified dividing cell
      tracking technique (DCT) were analyzed as well as the percentages of apoptotic
      cells. We also determined the levels of IFN-gamma, IL-2, IL-10 and IL-17A using
      Cytometric Bead Array Flex system in cell culture supernatants. RESULTS:
      CD4+CD28+ and CD8+CD28+ cells from the whole study group were characterized by
      shorter time required to enter the first (G1) phase of the first cell cycle at
      21% compared to 10% O2. Both T cell populations performed significantly more
      divisions at 21% O2. The percentages of dividing cells were also significantly
      higher at atmospheric O2. Interestingly, data analysis by gender showed that male
      lymphocytes had similar proliferative parameters at both O2 concentrations while
      female lymphocytes proliferate more efficiently (note from the author: we cannot
      say that lymphocytes proliferate faster, rather more effectively, because cells
      perform more divisions, which gives more percentage of offspring cells) at 21%
      oxygen. Compared to males, the female CD4+ cells showed increased susceptibility
      to apoptosis at both O2 concentrations. No differences in the levels of cytokines
      regardless of gender and oxygen conditions were found. CONCLUSIONS: We showed
      that in vitro female T cells (both CD4+ and CD8+ cells) are more sensitive than
      male lymphocytes to low O2 concentration as demonstrated by the decrease in their
      proliferation dynamics. The effect does not depend on increased apoptosis of
      female T cells under low O2 because percentage of apoptotic cells was similar at
      both O2 concentrations.

PMID- 28509315
TI  - Caspase-3 as an important factor in the early cytotoxic effect of nickel on oral
      mucosa cells in patients treated orthodontically.
AB  - INTRODUCTION: The effect of fixed orthodontic appliances on biochemical changes
      in saliva and pathophysiological status of the oral cavity is not clear. Recent
      data showed that nickel (Ni) released from orthodontic appliances can decrease
      cellular viability, induce DNA damage and apoptosis in oral mucosa cells. Since
      the mechanism of these Ni effects is unknown, the aim of our study was to analyze
      the expression of caspase-3 in epithelial cells of oral mucosa in healthy
      individuals treated orthodontically. MATERIAL AND METHODS: Twenty-eight
      volunteers participated in the study. Epithelial cells were collected from oral
      mucosa directly before appliance insertion, one week after the insertion, and 24
      four weeks after the insertion of fixed appliances. Cellular identification and
      measurements were conducted by light microscopy. Caspase-3 expression was
      evaluated immunochemically. Nickel concentration in saliva was also determined.
      RESULTS: A significantly higher number of oral epithelial cells with caspase-3
      immunoreactivity in was found one week, but not 24 weeks, after orthodontic
      treatment. The enhanced expression of caspase-3 was accompanied by increased
      nickel concentration in saliva. CONCLUSIONS: Our data suggests that nickel
      released from orthodontic appliances can activate caspase-3 and this mechanism
      may be partially responsible for the cytotoxic action of nickel in the oral
      cavity of orthodontically-treated individuals.

PMID- 28509316
TI  - Effects of 17beta-estradioland raloxifene on endothelial OPG and RANKL secretion.
AB  - OBJECTIVES: This study aims to asses the effects of estradiol vs. raloxifene on
      the levels of osteoprotegerin and soluble Receptor Activator of Nuclear Factor kB
      Ligand (sRANKL) in Human Umbilical Vein Endothelial Cells (HUVEC) culture in
      standard and calcifying medium. MATERIAL AND METHODS: Human Umbilical Vein
      Endothelial Cells were isolated from human umbilical vein by standard method. The
      supernatant concentrations of osteoprotegerin (OPG) and sRANKL (ELISA) were
      determined after incubation with glicerophosphate, estradiol , raloxifene,
      glicerophoshate and estradiol, glicerophosphate and raloxifene in comparison with
      control group at four designated time points (0, 1, 2 and 4 days of incubation).
      RESULTS: Incubation of estradiol with HUVEC colony lowered the OPG level
      significantly after day 2 and 4. Meantime, the level of sRANKL was stable.
      Raloxifene added to standard growth medium also significantly lowered OPG
      concentration after day 4 only, with no impact on sRANKL concentration. When
      added to calcifying medium, both estradiol and raloxifene significantly changed
      OPG level during the experiment. In all treated groups OPG levels were lower than
      in groups exposed to calcifying medium only. Neither estradiol, nor raloxifene
      changed sRANKL levels during the experiment. CONCLUSIONS: Estradiol and
      raloxifene affect OPG secretion from endothelial cells in vitro which may suggest
      their modifying role in pathogenesis of vascular calcification in postmenopausal
      women.

PMID- 28509317
TI  - Morphology of the cesarean section scar in the non-pregnant uterus after one
      elective cesarean section.
AB  - OBJECTIVES: A growing number of studies suggest that the incomplete healing of
      the CS scar in the uterus increase the risk of uterine dehiscence or rupture
      during subsequent pregnancies. Thus, the factors that affect wound healing should
      be evaluated. We aimed to determine whether the morphology of the CS scar in non
      pregnant women after one elective CS was affected by the site of the uterine
      incision, uterine flexion, maternal age, and fetal birth weight. MATERIAL AND
      METHODS: 208 non-pregnant women were invited for participation in the study, but
      only 101 of them met inclusion criteria. Standardized scar parameters (residual
      myometrial thickness (RMT), depth (D) and width (W) of the hypoechoic niche) were
      measured using ultrasonography at least 6 weeks after the CS. RESULTS: Scar
      defect was detected in 26 of 101 subjects. Women without scar defect had
      significantly higher RMT values (1.87 vs. 0.87), lower newborn birth weight (3127
      g vs. 3295 g), and higher scar location above the internal cervical os (62% vs.
      16%), than those with scar defect. Maternal age was significantly correlated with
      D value (R = 0.40). Uterine retroflexion was significantly correlated with a
      larger D value (R = 0.63) and a larger D/RMT ratio (R = 0.24). CONCLUSIONS: In
      low-risk women who have undergone one elective CS, several risk factors are
      associated with development of the scar defect, but only scar location can be
      modified during surgery. Future research is needed to determine whether a
      relatively higher incision location in the uterus can ensure optimal healing of
      the CS scar.

PMID- 28509318
TI  - The duration of pregnancy in ecologically-challenged area. The effects of
      environmental pollution with aromatic hydrocarbons on the angiogenesis and
      elements of the mesenchymal tissue of the human placenta.
AB  - INTRODUCTION: The literature presents only few reports regarding the effects of
      elevated levels of aromatic hydrocarbons (AH) on the functions of the human
      placenta. The effects of environmental contamination with AH (including phenol
      and 1-hydroxypyrene) have certain negative effects on parenchymal organs such as
      human placenta. OBJECTIVE: The paper aimed to assess the effects of elevated
      levels of AH on the placental angiogenesis and elements of the mesenchymal tissue
      of the placenta. MATERIAL AND METHODS: Tissue material from 50 afterbirths from
      Plock constituted a study group, whereas 50 afterbirths from Kutno constituted a
      control group. Immunohistochemical reactions with the peroxidase method using
      LSAB kits (DAKO) were performed. The extent and intensity of reactions were
      analysed. The levels of phenols and 1-hydroxypyrene in the excreted urine of
      pregnant women (undergoing delivery) were detected using gas chromatography and
      colorimetry. RESULTS: The levels of phenol and 1-hydroxypyrene in the excreted
      urine were demonstrated to be statistically significantly higher in patients
      living in the area of Plock. Statistically significantly higher expression of
      antibodies indicating placental angiogenesis was observed in the placentas in the
      Plock group (p < 0.01). Moreover, lower expression of vimentin indicating
      reactions with proteins in mesenchymal cells was observed in the Kutno group (p <
      0.01). CONCLUSIONS: Pregnancy in the environment with elevated levels of aromatic
      hydrocarbons has detrimental effects on the human placenta. The foetus is
      protected by activation of adaptation and compensation mechanisms that are
      manifested as significant angiogenesis and greater development and
      differentiation of mesenchymal cells compared to the control group.

PMID- 28509319
TI  - Investigation of cesarean sections at Konya Training and Research Hospital
      Obstetrics and Gynecology Department between 2010 and 2015.
AB  - OBJECTIVE: Analysis of the annual distribution of cesarean sections and
      indications between 2010 and 2015 in our clinic. MATERIAL AND METHODS: Medical
      records of 10,437 cesarean section patients from a total number of 24,283
      deliveries performed at Department of Obstetrics and Gynecology between 2010-2015
      were evaluated retrospectively. The indications for Cesarean section were
      analyzed and compared based on years. RESULTS: The lowest cesarean section rate
      was 18.67% in 2011 and the highest rate was 24.5% in 2013, and the annual rates
      were close to each other in this 6-year period (p > 0.05). History of uterine
      surgery was the indication with the highest rate of 49.52%, while fetal distress
      was the second most frequent with 12.53%; presentation anomalies were observed as
      the most frequent third indication with 7.55%, and umbilical cord prolapse was
      the least frequent indication with 0.33%. CONCLUSIONS: Patient education about
      normal delivery and providing means for pain control during normal delivery,
      improvement in physical conditions of the clinics, frequent and regular training
      of the assisting staff with obstetrics physicians are important to diminish the
      rates of primary cesarean sections. In addition, a normal delivery after a
      previous cesarean section must be encouraged.

PMID- 28509320
TI  - Premature fetal tissues are possible source of valuable mesenchymal stem cells.
AB  - OBJECTIVES: Comparison of the ability to inhibit alloactivated lymphocytes
      proliferation of human Wharton Jelly (WJ) and amniotic membrane (AM) mesenchymal
      stem cells (MSCs) from preterm and term pregnancies. MATERIAL AND METHODS: Term
      WJ-MSCs (n = 5) and Preterm-WJ-MSCs (n = 1) were obtained from tissue explants by
      adherent method. Term-AM-MSCs (n = 5) and Preterm-AM-MSCs (n = 1) were obtained
      by tripsin and collagenase digestion method. Term and Preterm MSCs phenotype was
      confirmed in vitro by flow cytometry. To evaluate the potential of fetal and
      adult MSCs to diminish immunological response mixed lymphocytes reaction (MLR)
      has been performed. RESULTS: Term and Preterm cells were positively identified as
      MSCs by the expression of CD73 and CD90 and CD105 with simultaneous absence of
      CD11b, CD14, CD19, CD34, CD45 and HLA-DR. The mean inhibition of allostimulated
      lymphocytes after addition of fetal derived MSCs amounted 64.8% for term AM-MSCs
      and 42.1% for term WJ-MSCs (for both populations the effect was statistically
      significant, p < 0.01). The addition of preterm-MSCs to MLR resulted in reduction
      of stimulated lymphocytes proliferation by 64.9% for AM-MSCs and 86.1% for WJ
      MSCs. CONCLUSIONS: Presented results suggest that preterm fetal tissues contain
      MSCs which posses similar immunosuppressive capacity as those from term
      pregnancies. In the future MSCs from the umbilical cord and amnion can be
      potentially used to prevent immuno-dependent injuries in premature newborns.

PMID- 28509321
TI  - Evaluation of tissue metalloproteinase inhibitor TIMP-1 and Survivin levels
      during third trimester pregnancy - a preliminary report.
AB  - OBJECTIVES: A proper implantation of trophoblastic cells and an appropriate
      metalloproteinases activity is required to cause disintegration of basal
      membranes of cells. The activity of tissue matrix metaloproteinases can be
      inhibited by their matrix inhibitors - TIMP-s. Survivin is a member of inhibitor
      of apoptosis proteins family (IAP), that suppresses caspase activation,
      influences VEGF expression and promotes proliferative action of endothelial
      cells. MATERIAL AND METHODS: The aim of the study was to assess concentrations of
      two independent anti-apoptotic factors. TIMP-1 and survivin in serum of women in
      their third trimester of pregnancy and in umbilical cord blood of neonates -
      drawn separately from veins and arteries. The study group consisted of 29
      pregnant women in physiological pregnancy and with correct fetal development, in
      gestational age between 37 to 40 weeks of gestation. Blood used in the study was
      collected from maternal cubital fossa veins and from neonatal umbilical cords
      (from veins and from arteries separately). The research was conducted using TIMP
      1 and Survivin ELISA kits from R & D Systems according to manufacturers'
      recommendations and protocols. RESULTS: The concentrations of TIMP-1 were similar
      and independent of the source of blood samples. Arterial values of TIMP-1 in
      umbilical cord compared to maternal and fetal veins were slightly lower, but no
      statistical difference was found. The mean concentrations of Survivin were
      comparable but we found that in some cases the results in cord blood serum in
      both vessels-vein and arteries were almost negative. Arterial values of Survivin
      in umbilical cord compared to maternal blood were higher, but no statistical
      difference was found. CONCLUSIONS: In III-rd trimester of pregnancy parameters of
      Timp-1 and Survivin - anti-apoptotic substances concentration were similar in
      maternal and cord blood in both artery and vein. We found no increased activity
      of selected antiapoptotic factors.

PMID- 28509322
TI  - Polymorphic variants of genes involved in choline pathway and the risk of
      intrauterine fetal death.
AB  - OBJECTIVES: Choline and folate metabolism disturbances may be involved in the
      occurrence of intrauterine fetal death (IUFD). The proper activity of this
      metabolism could be determined by genetic variants involved in choline pathway
      e.g. CHKA (gene encoding choline kinase alpha), PCYT1A (gene encoding CCTalpha)
      and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining
      the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A
      rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD
      occurrence. MATERIAL AND METHODS: The study involved 76 mothers with IUFD
      occurrence and 215 mothers of healthy children. Genetic analysis was performed
      with the use of PCR/RFLP method. RESULTS: The frequency of genotypes and alleles
      of studied polymorphisms was similar in both groups. The study revealed no
      association of PCYT1A, CHKA and CHDH polymorphisms in analysed groups of women.
      While evaluating the co-existence of analysed polymorphisms statistically
      significant correlation was revealed. Co-existence of CHKA rs7928739 AC/CHDH
      rs2289205 AA genotypes was observed statistically more frequently in the study
      group than in the control group (p = 0,031). CONCLUSIONS: There is no correlation
      between single CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363
      and CHDH rs2289205 polymorphisms and the incidence of intrauterine fetal death.
      However, revealed statistically significant difference between co-existence of
      CHKA rs7928739 AC/CHDH rs2289205 AA genotypes between study groups suggest the
      need of further analysis.

PMID- 28509323
TI  - Triple negative endometrial cancer.
AB  - Endometrial cancer (EC) is the most common malignancy of the female genital tract
      in the developed countries. In Poland, EC incidence increased from 3.496 to 5.251
      between 2000 and 2011, with 5.251 new cases were diagnosed in 2011 alone, and
      this upward trend is expected to continue. There are two types of endometrial
      cancer: estrogen- related type I (approximately 80% of the cases) and unrelated
      to estrogen type II. Type I includes adenocarcinomas which grow slowly, have
      better prognosis, superficially infiltrate the myometrium, originate from
      endometrial hyperplasia without atypia, and occur before and after menopause. The
      most common type I mutations include PTEN, KRAS and microsatellite instability.
      Type II is represented by serous, mucinous, clear-cell carcinomas, with
      aggressive behavior associated with poor prognosis, high risk of distant
      metastases at diagnosis, deeper infiltration of the uterine muscle, often to
      serosa, originating from the atrophic endometrium, and typically presenting after
      menopause. The most common type II mutations include TP53, HER-2 and P16.

PMID- 28509324
TI  - Three-dimensional neurosonography - a novel field in fetal medicine.
AB  - Neurosonography is a promising technique for prenatal diagnosis, combining
      features of ultrasound imaging with fetal neurology. The brain is a three
      dimensional structure, therefore observing brain structure in the three basic
      planes (sagittal, coronal and axial) is mandatory. The anterior fontanelle and
      sagittal suture may serve as acoustic ultrasound windows in the transvaginal
      brain scan, allowing to obtain high-resolution neuroimages of the intracranial
      structures. Furthermore, three-dimensional (3D) ultrasound combined with the
      transvaginal brain approach provides detailed and sophisticated neuroimages.
      Three orthogonal planes of the brain, tomographic ultrasound imaging (TUI) and
      other off-line approaches (e.g. volume contrast imaging (VCI) or HDlive
      silhouette imaging) may be obtained from a single 3D dataset. 3D Doppler
      ultrasound enables visualization of the intracerebral vascularity, allowing to
      obtain more precise information on cerebral perfusion. Various abnormal brain
      conditions, including ventriculomegaly, agenesis of the corpus callosum,
      posterior fossa abnormalities and others, can be well-demonstrated. Due to high
      rates of the associated anomalies and uncertain prognosis, any suspicion of CNS
      abnormalities shall imply detailed ultrasonographic evaluation of the fetal
      anatomy to exclude the associated anomalies. Despite a growing number of
      neuroimaging modalities, prenatal counselling remains a challenge as prediction
      of brain functionality and the neurological prognosis often remain uncertain. New
      investigations on the relations between various migration disorders and gene
      mutations, as well as recent clinical research on the relations between
      neuroimaging detection of local migration disorders using sophisticated imaging
      technologies and the postnatal neurological prognosis will contribute to the
      development of maternal-fetal medicine as well as pediatric neurology.

PMID- 28509325
TI  - An alternative approach to gynecological wound healing.
AB  - An 89-year-old woman was reffered to our Clinic with vulvar cancer. She also
      suffered from obesity [with body mass index (BMI) 35 kg/m2], persistent
      hypertension, diabetes mellitus type 2 treated with oral medications. In 2015 she
      underwent a surgery due to endometrial carcinoma. Total abdominal hysterectomy
      with bilateral salphingoophorectomy, omentectomy and pelvical node dissection was
      performed (histopathology revealed adenocarcinoma serosum G2; FIGO stage Ib). In
      January 2016 after vulvar ulceration biopsy plano-epithelial squamous vulvar
      cancer was diagnosed. She was referred to surgery. She has undergone an operation
      in October 2016. She was admitted to gynaecological unit at our institution.
      Physical examination revealed mutilated vulva with excised labia major, labia
      minor, and narrowing of vaginal orifice. The right side shown tumor 2.5 cm in
      diameter, with slough area and no deep infiltration and satellital nodule on the
      left labia majora 1cm in diameter. The cervix, vaginal wall, rectum and anus
      appeared normal. There were no enlarged lymph nodes at the inguinal area.

PMID- 28509326
TI  - Polish Gynecological Society Recommendations for Labor Induction.
AB  - Labor induction involves artificial stimulation of childbirth before the natural,
      spontaneous onset of labor. It is one of the most common procedures in modern
      obstetrics. The frequency of labor induction has doubled in recent decades due to
      the development of perinatology and methods of monitoring fetal well-being in
      particular. Currently, one in five pregnant women and 30-40% of women delivering
      vaginally undergo this procedure. Reasons for induction include reduction of the
      perinatal mortality and morbidity of the fetus and newborn, as well as the
      reduction of maternal complications. However, as every medical intervention,
      labor induction is associated with a risk of complications.

PMID- 28509327
TI  - The occurrence of hepatocellular carcinoma in different risk stratifications of
      clinically noncirrhotic nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular
      carcinoma (HCC), but its high prevalence challenges current surveillance
      strategies. We aimed to evaluate HCC incidences in different risk stratifications
      for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research
      Database, we located 31,571 patients with NAFLD between the years 1998 and 2012.
      After excluding other causes of hepatitis, underlying cirrhosis or malignancy,
      18,080 patients were recruited for final analysis. Cumulative incidences of HCC
      were analyzed after adjusting for competing mortality. With a median follow-up
      duration of 6.32 years in the study cohort, the 10-year cumulative incidence of
      HCC was 2.73% [95% confidence interval (CI): 1.69-3.76%]. Hepatoprotectant was
      used as a surrogate marker for elevated serum alanine transaminase (ALT). After
      adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus,
      gout, statin use, metformin use and aspirin use, elevated ALT was independently
      associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00
      15.42; p < 0.001]. Multivariate stratified analysis verified this association in
      all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05
      1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as
      independent risk factors. The 10-year cumulative HCC incidence was highest in
      older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%),
      but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%).
      The incidence of HCC was relatively low in patients with clinically noncirrhotic
      NAFLD, however, HCC risk was significantly increased in older patients
      experiencing an elevated serum ALT.

PMID- 28509328
TI  - Anatomy-based DMEK Wetlab in Homburg/Saar: Novel aspects of donor preparation and
      host maneuvers to teach descemet membrane endothelial keratoplasty.
AB  - Use of Descemet Membrane Endothelial Keratoplasty (DMEK) has been limited because
      of problems with donor preparation, i.e. tearing of the Descemet membrane and
      difficulties in unfolding the Endothelium-Descemet-Membrane-Layer (EDML) in the
      anterior chamber (AC). The purpose of this work was to describe a novel approach
      to teaching anatomy-based donor and recipient preparation in a DMEK-Wetlab. We
      teach successful mono-manual donor preparation of human corneas in organ culture
      not suitable for transplantation, including peripheral markers for orientation.
      We also teach safe recipient preparation in a freshly-enucleated pig eye in organ
      culture preservation medium for atraumatic introduction of the EDML roll into the
      AC, reliable orientation of the EDML during surgery, and stepwise unfolding
      within the AC. Twenty-two candidates in the 1. Homburg Cornea Curriculum HCC 2015
      who practiced both preparations using three human donor corneas and three pig
      eyes assessed the procedure as follows: (1) overall grade of the Wetlab 1.4
      (median 1, range 1 to 2 - on a scale from 1 (excellent) to 6 (terrible); (2) most
      participants and tutors stated that the Wetlab is most effective for colleagues
      who have some previous experience with corneal microsurgery. Our novel anatomy
      based approach to simulating donor preparation and graft implantation for DMEK
      seems to meet the expectations and requirements of colleagues with previous
      experience in corneal microsurgery and will help to reduce the rate of
      complications for incipient DMEK surgeons in the future. Clin. Anat. 31:16-27,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28509329
TI  - A case of combined desmoplastic trichoepithelioma and compound melanocytic nevus.

PMID- 28509330
TI  - Malignancies in hepatitis C virus-positive and -negative kidney transplant
      recipients: A case-controlled study.
AB  - BACKGROUND: Malignancies and lymphoma are common complications after kidney
      transplantation. However, no link has been made between the incidence of
      malignancies and hepatitis C virus (HCV) infection in this setting. This case
      controlled study compared the incidence of malignancies, including lymphoma,
      between kidney transplant (KT) patients with or without HCV replication. PATIENTS
      AND METHODS: A total of 99 HCV-positive RNA-positive KT patients were matched
      with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of
      transplantation, and were followed for 145.8+/-78.4 months. RESULTS: During the
      follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and
      64 (32%) patients developed cancer in the HCV-negative group (P=not significant
      [ns]). Survival without a cancer was similar between both groups. Thirteen HCV
      positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV
      negative patients (P=ns). Survival without a solid cancer was similar between
      both groups. Three patients from the HCV-positive and 4 from the HCV-negative
      group developed a lymphoma. Only 2 patients from the HCV group died from
      hepatocellular carcinoma. Survival without a skin cancer was similar between both
      groups. Patient and death-censored graft survival rates were significantly lower
      in the HCV group. CONCLUSION: The incidences and types of malignancies were
      similar in the HCV-positive and HCV-negative KT patients.

PMID- 28509331
TI  - Anatomic landmarks in lacrimal surgery from an ophthalmologist's point of view:
      Clinical findings of external dacryocystorhinostomy and dacryoendoscopy.
AB  - Epiphora is a common clinical symptom of nasolacrimal duct obstruction. However,
      it is present in several pathologies and can lead to decreased quality of life
      for patients. A careful clinical examination including a detailed patient's
      history and diagnostic tests such as the fluorescein dye disappearance test and
      diagnostic syringing of the lacrimal duct are essential. Depending on the time of
      presentation (congenital, primary, or secondary acquired), grade (subtotal or
      total) and location of the stenosis, different surgical approaches can be
      considered. These are subdivided into minimally invasive (transcanalicular) and
      anastomosing (dacryocystorhinostomy) procedures. Furthermore, the anatomical
      landmarks and the site of surgical intervention differentiate the surgical
      techniques into endoscopic or transcutaneous. Modern intubation techniques offer
      a large spectrum of therapeutic possibilities enabling patient care to be
      customized and individualized. Knowledge of the topographical anatomy is crucial
      for achieving greater success and a lower complication rate. Clin. Anat. 30:1034
      1042, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28509334
TI  - Enantioselective Synthesis of Tetrahydroquinolines by Borrowing Hydrogen
      Methodology: Cooperative Catalysis by an Achiral Iridacycle and a Chiral
      Phosphoric Acid.
AB  - We report herein the highly enantioselective synthesis of 2-substituted
      tetrahydroquinolines through borrowing hydrogen, a process recognized for its
      environmentally benign and atom-economical nature. The use of an achiral
      iridacycle complex in combination with a chiral phosphoric acid as catalysts was
      the key to the development of this highly efficient and enantioselective
      transformation.

PMID- 28509332
TI  - Myeloid but not epithelial tissue factor exerts protective anti-inflammatory
      effects in acid aspiration-induced acute lung injury.
AB  - : Essentials Tissue factor (TF) represents a central link between hemostasis and
      inflammation. We studied the roles of myeloid and airway epithelial TF in acid
      caused acute lung injury (ALI). TF on myeloid cells displays a non-coagulatory
      role regulating the inflammatory response in ALI. Airway epithelial TF
      contributes to hemostatic functions, but is dispensable in ALI pathogenesis.
      SUMMARY: Introduction Acute lung injury (ALI) is a life-threatening condition
      characterized by damaged alveolar-capillary structures and activation of
      inflammatory and hemostatic processes. Tissue factor (TF) represents a crucial
      link between inflammation and coagulation, as inflammatory mediators induce
      myeloid TF expression, and TF initiates extrinsic coagulation. Objective As
      pulmonary inflammation stimulates TF expression and TF modulates immune
      responses, we aimed to elucidate its impact on ALI. In particular, we wanted to
      distinguish the contributions of TF expressed on airway epithelial cells and TF
      expressed on myeloid cells. Methods Mice with different cell type-specific TF
      deficiency and wild-type littermates were intratracheally treated with
      hydrochloric acid, and leukocyte recruitment, cytokine levels, thrombin
      antithrombin (TAT) complexes and pulmonary protein-rich infiltrates were
      analyzed. Results Our data demonstrate that a lack of epithelial TF did not
      influence acute responses, as bronchoalveolar neutrophil accumulation 8 h after
      ALI induction was unaltered. However, it led to mild, prolonged inflammation, as
      pulmonary leukocyte and erythrocyte numbers were still increased after 24 h,
      whereas those in wild-type mice had returned to basal levels. In contrast,
      myeloid TF was primarily involved in regulating the acute phase of ALI without
      affecting local coagulation, as indicated by increased bronchoalveolar neutrophil
      infiltration, pulmonary interleukin-6 levels, and edema formation, but equal TAT
      complex formation, 8 h after ALI induction. This augmented inflammatory response
      associated with myeloid TF deficiency was confirmed in vitro, as
      lipopolysaccharide-stimulated TF-deficient alveolar macrophages released
      increased levels of chemokine (C-X-C motif) ligand 1 and tumor necrosis factor
      alpha as compared with wild-type macrophages. Conclusion We conclude that myeloid
      TF dampens inflammation in acid-induced ALI.

PMID- 28509335
TI  - Dignity-conserving care actions in palliative care: an integrative review of
      Swedish research.
AB  - BACKGROUND: Previous research has proposed that persons in need of palliative
      care often have a loss of functions and roles that affects social and existential
      self-image. Moreover, these individuals also commonly suffer from complex
      multisymptoms. This, together with the situation of facing an impending death,
      can lead to a loss of dignity. Therefore, supporting these persons' dignity is a
      crucial challenge for professional nurses. The 'Dignity Care Intervention'
      addresses the multidimensionality of dignity by identifying patients' dignity
      related concerns and suggests care actions to address them. At the present, the
      Dignity Care Intervention is adapted for implementation in Swedish care settings.
      Because expressions of dignity are influenced by culture, and an overview of care
      actions in a Swedish context is lacking, this integrative review aimed to find
      suggestions from Swedish research literature on what kind of care actions can
      preserve dignity. METHODS: An integrative literature review was conducted using
      the databases SwePub and SweMed+. Articles published from 2006 to 2015 and theses
      published from 2000 to 2015 were searched for using the terms 'dignity' and
      'palliative care'. Result sections of articles and theses were reviewed for
      dignity-conserving care actions synthesised by thematic analysis and categorised
      under themes and subthemes in Chochinov's model of dignity. RESULTS: Fifteen
      articles and 18 theses were included together providing suggestions of care
      actions in all themes and subthemes in the dignity model. Suggested care actions
      included listening, communication, information, symptom control, facilitating
      daily living and including patients in decision-making. Additionally, nurses'
      perceptiveness towards the patients was a core approach. CONCLUSION: The review
      offers culturally relevant suggestions on how to address specific dignity-related
      concerns. The adapted Dignity Care Intervention will be a way for Swedish nurses
      to provide person-centred palliative care that will conserve patients' dignity.

PMID- 28509333
TI  - Altered glycan accessibility on native immunoglobulin G complexes in early
      rheumatoid arthritis and its changes during therapy.
AB  - The goal of this study was to investigate the glycosylation profile of native
      immunoglobulin (Ig)G present in serum immune complexes in patients with
      rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting
      the accessibility of glycans present on IgG-containing immune complexes by
      biotinylated lectins, were employed. Lectins capturing fucosyl residues (AAL),
      fucosylated tri-mannose N-glycan core sites (LCA), terminal sialic acid residues
      (SNA) and O-glycosidically linked galactose/N-acetylgalactosamine (GalNac-L) were
      used. Patients with recent-onset RA at baseline and after 3-year follow-up were
      investigated. We found that native IgG was complexed significantly more often
      with IgM, C1q, C3c and C-reactive protein (CRP) in RA patients, suggesting
      alterations of the native structure of IgG. The total accessibility of fucose
      residues on captured immune complexes to the respective lectin was significantly
      higher in patients with RA. Moreover, fucose accessibility on IgG-containing
      immune complexes correlated positively with the levels of antibodies to cyclic
      citrullinated peptides (anti-CCP). We also observed a significantly higher
      accessibility to sialic acid residues and galactose/GalNAc glyco-epitopes in
      native complexed IgG of patients with RA at baseline. While sialic acid
      accessibility increased during treatment, the accessibility of galactose/GalNAc
      decreased. Hence, successful treatment of RA was associated with an increase in
      the SNA/GalNAc-L ratio. Interestingly, the SNA/GalNAc-L ratio in particular rises
      after glucocorticoid treatment. In summary, this study shows the exposure of
      glycans in native complexed IgG of patients with early RA, revealing particular
      glycosylation patterns and its changes following pharmaceutical treatment.

PMID- 28509336
TI  - Application of the movement disorder society prodromal Parkinson's disease
      research criteria in 2 independent prospective cohorts.
AB  - BACKGROUND: The research criteria for prodromal PD of the MDS propose a new
      approach for the assessment of the individual probability of prodromal PD. These
      criteria require a testing of their reliability in different prospective cohorts.
      OBJECTIVES: The objective was to evaluate the MDS prodromal PD criteria in 2
      independent prospective studies. METHODS: Prodromal PD probabilities of the
      Tubingen Evaluation of Risk Factors for Early Detection of Neurodegeneration
      cohort (TREND study, n = 650, recruited by the presence of probable rapid eye
      movement sleep behavior disorder, depression, and/or hyposmia or none of these at
      baseline and 2-, 4-, and 6-year follow-up) and the population-based Prospective
      Evaluation of Risk Factors for Idiopathic Parkinson's Syndrome cohort (PRIPS
      Tubingen subsample; n = 715, baseline and 3- and 5-year follow-up) were
      calculated. Baseline posttest probabilities, time to PD diagnosis, marker
      constellations, and longitudinal changes of prodromal PD probabilities were
      analyzed. RESULTS: Incident PD cases (TREND, n = 10; PRIPS = 7) showed
      significantly higher likelihood ratios of risk and prodromal markers at baseline
      when compared with nonconverters. Only 2 of 17 incident PD cases met the criteria
      for probable prodromal PD (ie, posttest probability > 80%) and 5 had possible
      prodromal PD (ie, > 50%) 1.4 to 3.8 years before diagnosis. The criteria showed
      high specificity and negative predictive values (>98%), but low sensitivity
      (TREND, 30%; PRIPS, 14%) and positive predictive values (TREND, 19%, PRIPS, 50%).
      The individual risk for prodromal PD in incident PD cases showed an inverse
      correlation with the time to conversion (Spearman rho = .80, P = .006) and unlike
      in nonconverters, increased during follow-up. CONCLUSION: The MDS prodromal
      criteria provide a practical framework for the calculation of prodromal PD risk.
      Although specificity of the criteria is high, most patients will not meet the
      criteria before diagnosis unless testing is thoroughly performed with numerous
      and highly specific markers objectively assessed. (c) 2017 International
      Parkinson and Movement Disorder Society.

PMID- 28509337
TI  - Impact of induction chemotherapy, hyperfractionated accelerated radiotherapy and
      high-dose thiotepa on brain volume loss and functional status of children with
      primitive neuroectodermal tumour.
AB  - BACKGROUND: The introduction of aggressive chemo-radiotherapy regimens has
      improved overall survival in children with primitive neuroectodermal tumours
      (PNET). However, these combinations may result in neurotoxicity. Previously
      reported magnetic resonance imaging abnormalities in children receiving intensive
      sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and
      high-dose thiotepa prompted us to investigate the degree of brain volume loss and
      patients' functional status after therapy. METHODS: We retrospectively reviewed
      clinico-radiological data of children with PNET treated in this way at our
      centre. RESULTS: We studied 14 children treated between December 2009 and April
      2013. Data were not complete for one child. Performance status was severely
      restricted in four children, and mildly to moderately impaired in 7 of the 13
      children. Eleven of 13 children showed mild-to-severe generalised
      neuroparenchymal atrophy, in 7 of whom neuroparenchymal volume loss was moderate
      to severe. Of these seven, six had received high-dose thiotepa. There was no
      correlation between brain volume loss and Lansky performance status. However,
      unexpected neurotoxicities, such as symptoms of transverse myelitis, were
      observed. CONCLUSION: Measurement of brain volume loss in patients treated with
      HART and high-dose thiotepa may not be sufficient to predict function. However,
      correlation of brain volume loss due to late neurotoxicity with performance
      decline may be more obvious over longer period of follow-up. The combination of
      HART and myeloablative courses of thiotepa is associated with severe
      neurotoxicity and subsequent decline in performance status in a significant
      proportion of patients.

PMID- 28509338
TI  - Investigation of the ischioanal fossa: Application to abscess spread.
AB  - The location of perianal abscesses and the course of the fistula follow certain
      patterns, especially in the relationship between external and internal openings.
      However, it is still not clear how the contents of the ischioanal fossa,
      especially the fibrous network of fat tissue, affect the route for such diseases.
      Ten male adult cadavers were selected for the study. Seven horizontal transverse
      section planes from 1 cm above the pubic symphysis to the inferior border of the
      lesser trochanter of the femur were recorded after P45 sheet plastination. We
      observed characteristics of fiber distribution in the ischioanal fossa and its
      relationship with surrounding structures in every plane. There was a dense strip
      type fiber connecting with junction fascia between the obturator internus and
      gluteus maximus muscles. Close to the levator ani, obturator internus, and
      gluteus maximus, the fibers were very dense and continuous with the fascia on the
      surfaces of these three muscles. The function of the fibrous network was
      considered to be not only the support of fat tissue in the fossa but also
      cushioning during physiological actions such as defecation. We hope that these
      morphological results could help to elucidate the passage of fistulae and the
      locations susceptible to perianal abscesses. Clin. Anat. 30:1029-1033, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28509341
TI  - The US cancer moonshot-A need and opportunity for primary care participation and
      collaboration.

PMID- 28509339
TI  - Comparison of JAK2V617F -positive essential thrombocythaemia and early primary
      myelofibrosis: The impact of mutation burden and histology.
AB  - An accurate histological diagnosis may distinguish essential thrombocythaemia
      (ET) from early primary myelofibrosis (early-PMF), which is associated with worse
      outcome. Outcome of ET is also negatively affected by the presence of the
      JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and
      histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF
      JAK2V617F -positive patients followed in 4 Italian haematology centers. JAK2V617F
      allele burden was <=50% in 90% and 87% of ET and early-PMF patients, respectively
      (P = .34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients
      experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients
      evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28
      (5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality
      rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P =
      .45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only
      progression to overt myelofibrosis at 10 years was significantly worse (11.4% and
      1.5%, P = .004). In multivariate analysis, a higher (>50%) JAK2V617F burden was
      significantly correlated with fibrotic progression and histology. Considering
      JAK2V617F -positive disease, a higher (>50%) JAK2V617F burden and histological
      classification are independent prognostic risk factors for disease progression.
      These findings reinforce the need for standardized detection of this mutation.

PMID- 28509340
TI  - Platelet-rich fibrin-based matrices to improve angiogenesis in an in vitro co
      culture model for bone tissue engineering.
AB  - In the context of prevascularization strategies for tissue-engineering purposes,
      co-culture systems consisting of outgrowth endothelial cells (OECs) and primary
      osteoblasts (pOBs) have been established as a promising in vitro tool to study
      regeneration mechanisms and to identify factors that might positively influence
      repair processes such as wound healing or angiogenesis. The development of
      autologous injectable platelet-rich fibrin (PRF), which can be generated from
      peripheral blood in a minimal invasive procedure, fulfils several requirements
      for clinically applicable cell-based tissue-engineering strategies. During this
      study, the established co-culture system of OECs and pOBs was mixed with
      injectable PRF and was cultivated in vitro for 24 h or 7 days. The aim of this
      study was to analyse whether PRF might have a positive effect on wound healing
      processes and angiogenic activation of OECs in the co-culture with regard to
      proinflammatory factors, adhesion molecules and proangiogenic growth factor
      expression. Histological cell detection revealed the formation of lumina and
      microvessel-like structures in the PRF/co-culture complexes after 7 days of
      complex cultivation. Interestingly, the angiogenic activation of OECs was
      accompanied by an upregulation of wound healing-associated factors, as well as by
      a higher expression of the proangiogenic factor vascular endothelial growth
      factor, which was evaluated both on the mRNA level as well as on the protein
      level. Thus, PRF might positively influence wound healing processes, in
      particular angiogenesis, in the in vitro co-culture, making autologous PRF-based
      matrices a beneficial therapeutic tool for tissue-engineering purposes by simply
      profiting from the PRF, which contains blood plasma, platelets and leukocytes.

PMID- 28509342
TI  - Morphological and molecular characterization of Bysmatrum subsalsum (Dinophyceae)
      from the western Mediterranean Sea reveals the existence of cryptic species.
AB  - Bysmatrum subsalsum is a cosmopolitan dinoflagellate species that inhabits marine
      and transitional habitats. Despite its wide distribution, information on the
      morphological variability, phylogeny and ecology of B. subsalsum is scarce. In
      this study, we provide morphological and molecular data on B. subsalsum strains
      and wild cells from different locations in the Mediterranean Basin. The dynamics
      of cell abundances and the associated environmental conditions during a field
      bloom are also described. Genetic sequences of B. subsalsum obtained in this
      study showed large intraspecific differences, clustering in two well
      differentiated clades. Despite a certain degree of variation with respect to cell
      size, apical pore complex (APC) morphology and size, and cingulum displacement,
      cells from the two clades showed similar morphological traits. These findings
      indicated the occurrence of cryptic species. Comparisons of the morphology of our
      B. subsalsum specimens with the few descriptions available in the literature
      revealed larger than previously known intraspecific morphological variability.
      Phylogenetic trees inferred from the concatenated SSU, 5.8S-ITS, and LSU rRNA and
      the individual 5.8S-ITS regions suggested the inclusion of Bysmatrum in the
      Peridiniales and a close phylogenetic relationship with Peridinium sensu stricto.
      However, the low statistical support prevented the assignment of Bysmatrum to a
      particular family of Peridiniales. Ecological data obtained from a bloom in La
      Pletera salt marshes (Catalan Coast, Spain) suggested the species reaches high
      cell abundances at water temperatures >20 degrees C and salinity levels >30. Our
      results add new information regarding the morphology, phylogeny, and ecology of
      B. subsalsum.

PMID- 28509343
TI  - The influence of vascular risk factors on cognitive function in early Parkinson's
      disease.
AB  - OBJECTIVES: Hypertension, dyslipidemia, diabetes, and obesity are well
      established risk factors for cognitive impairment and dementia in older adults.
      In contrast, previous studies that have assessed the impact of vascular risk
      factors (VRFs) on cognition in Parkinson's disease (PD) have had methodological
      limitations and reported conflicting findings. We address this question in a
      large well-characterized cohort of de novo PD patients. METHODS: A total of 367
      untreated and non-demented patients aged 50 years and older with early PD (H&Y =
      1.0-2.0) underwent a comprehensive clinical and neuropsychological assessment at
      baseline and 24 months later. A series of linear mixed models were used to
      determine the effects of VRFs on cognition while controlling for patient and
      disease characteristics. The outcomes included norm-referenced Z-scores of global
      cognition, visuospatial skills, verbal episodic memory, semantic verbal fluency,
      attention, and working memory tests. RESULTS: A longer history of hypertension
      and a higher pulse pressure were significant predictors of lower Z-scores on
      immediate and delayed free recall, recognition, and verbal fluency tests. On
      average, every 10 mmHg increase in pulse pressure was associated with a 0.08
      reduction on the cognitive Z-scores. The effects were independent of age,
      education, disease duration, motor impairment, medication, and depressive
      symptoms. Other VRFs were not associated with cognitive outcomes. CONCLUSIONS:
      Our results are consistent with previous studies suggesting that hypertension
      exerts a detrimental effect on memory and verbal fluency in early PD. Management
      of blood pressure and cardiovascular health may be important to reduce risk of
      cognitive decline in PD. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28509345
TI  - Early First-Trimester Transvaginal Sonographic Diagnosis of Maternal Ureterocele.

PMID- 28509344
TI  - cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho
      Kinase-MLC phosphatase signaling pathway.
AB  - : Essentials Platelet shape change requires cytoskeletal rearrangement via myosin
      mediated actin contraction. We investigated whether nitric oxide (NO) affected
      thrombin-induced platelet shape change. NO inhibits shape change, RhoA/ROCK
      signalling and myosin light chain (MLC) phosphorylation. NO promotes MLC
      phosphatase activity, thus prevents MLC phosphorylation and shape change.
      SUMMARY: Background Platelet shape change, spreading and thrombus stability
      require activation of the actin cytoskeleton contractile machinery. The
      mechanisms controlling actin assembly to prevent unwanted platelet activation are
      unclear. Objectives We examined the effects of nitric oxide on the signaling
      pathways regulating platelet actin-myosin activation. Results S
      nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and
      myosin phosphorylation of the myosin light chain (MLC). Because thrombin
      stimulates phospho-MLC through the RhoA/ ROCK dependent inhibition of MLC
      phosphatase (MLCP) we examined the effects of NO on this pathway. Thrombin caused
      the GTP loading and activation of RhoA, leading to the ROCK-mediated
      phosphorylation of MLCP on threonine 853 (thr853 ), which is known to inhibit
      phosphatase activity. Treatment of platelets with GSNO blocked ROCK-mediated
      increases in phosphoMLCP-thr853 induced by thrombin. This effect was mimicked by
      the direct activator of protein kinase G, 8-pCPT-PET-cGMP, and blocked by the
      inhibition of guanylyl cyclase, but not inhibitors of protein kinase A. Further
      exploration of the mechanism demonstrated that GSNO stimulated the association of
      RhoA with protein kinase G (PKG) and the inhibitory phosphorylation (serine188)
      of RhoA in a cGMP-dependent manner. Consistent with these observations, in vitro
      experiments revealed that recombinant PKG caused direct phosphorylation of RhoA.
      The inhibition of RhoA by GSNO prevented ROCK-mediated phosphorylation and
      inhibition of MLCP activity. Conclusions These data suggest novel crosstalk
      between the NO-cGMP-PKG and RhoA/ROCK signaling pathways to control platelet
      actin remodeling.

PMID- 28509346
TI  - Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A
      immunostained sections in diagnosis of cervical intraepithelial neoplasia.
AB  - Visual interpretation of cervical biopsies is subjective and variable, generally
      showing fair to moderate inter-reader agreement in distinguishing high from low
      grade cervical intraepithelial neoplasia (CIN). We investigated the performance
      of two objective p16 quantitative tests in comparison with visual assessment: (i)
      p16-mRNA assay and (ii) digital analysis of sections stained for p16 protein. The
      primary analysis considered 232 high-risk human papilloma virus positive (HPV+)
      samples from diagnostic cervical specimens. A p16 RT-qPCR (p16-mRNA assay) was
      run on mRNA extracted from formalin-fixed paraffin-embedded sections. Two p16
      immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual
      IHC) and a digital read of a high-resolution scan (Digital IHC), were done on
      adjacent sections. The worst reviewed CIN grade (agreed by at least two
      histopathologists) from up to two biopsies and a loop excision was taken, with
      CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI
      61-77) for 85% (95%CI 77-91%) sensitivity. The four-point Visual IHC staining
      area under the curve (AUC) was 0.77 (95%CI 0.71-0.82), compared with 0.71 (95%CI
      0.64-0.77) for p16-mRNA and 0.67 (95%CI 0.60-0.74) for Digital IHC. Spearman rank
      order correlations were: visual to p16-mRNA 0.41, visual to digital 0.49 and p16
      mRNA to digital: 0.22. The addition of p16-mRNA assay to visual reading of p16
      IHC improved the AUC from 0.77 to 0.84 (p = 0.0049). p16-mRNA testing may be
      complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or
      perhaps a substitute in locations with a lack of skilled pathologists.

PMID- 28509348
TI  - Reconstitution of the plant ubiquitination cascade in bacteria using a synthetic
      biology approach.
AB  - Ubiquitination modulates nearly all aspects of plant life. Here, we reconstituted
      the Arabidopsis thaliana ubiquitination cascade in Escherichia coli using a
      synthetic biology approach. In this system, plant proteins are expressed and then
      immediately participate in ubiquitination reactions within E. coli cells.
      Additionally, the purification of individual ubiquitination components prior to
      setting up the ubiquitination reactions is omitted. To establish the
      reconstituted system, we co-expressed Arabidopsis ubiquitin (Ub) and
      ubiquitination substrates with E1, E2 and E3 enzymes in E. coli using the Duet
      expression vectors. The functionality of the system was evaluated by examining
      the auto-ubiquitination of a RING (really interesting new gene)-type E3 ligase
      AIP2 and the ubiquitination of its substrate ABI3. Our results demonstrated the
      fidelity and specificity of this system. In addition, we applied this system to
      assess a subset of Arabidopsis E2s in Ub chain formation using E2 conjugation
      assays. Affinity-tagged Ub allowed efficient purification of Ub conjugates in
      milligram quantities. Consistent with previous reports, distinct roles of various
      E2s in Ub chain assembly were also observed in this bacterial system. Therefore,
      this reconstituted system has multiple advantages, and it can be used to screen
      for targets of E3 ligases or to study plant ubiquitination in detail.

PMID- 28509347
TI  - Domain-specific cognitive impairment in non-demented Parkinson's disease
      psychosis.
AB  - INTRODUCTION: In Parkinson's disease (PD), psychosis is associated with cognitive
      impairment that may be more profound in particular cognitive domains. Our goal
      was to determine whether psychosis in non-demented PD participants is associated
      with domain-specific cognitive impairment on the Mini-Mental State Exam (MMSE).
      METHODS: The Morris K. Udall Parkinson's Disease Research Center of Excellence
      Longitudinal Study at Johns Hopkins is a prospective study that was initiated in
      1998. Clinical assessments are conducted at two-year intervals at the Johns
      Hopkins Hospital. We analyzed data from 137 enrolled participants with idiopathic
      PD. Psychosis diagnoses were established by psychiatrist interview per DSM-IV
      criteria. An incident dementia diagnosis resulted in exclusion from analysis for
      that evaluation and any future evaluations in that participant. We used logistic
      regression with generalized estimated equations (GEE) to model the time-varying
      relationship between MMSE subscale scores and psychosis, adjusting for potential
      confounding variables identified through univariable analysis. RESULTS: Thirty
      one unique psychosis cases were recorded among non-demented participants. Fifty
      total evaluations with psychosis present were analyzed. In multivariable
      regressions, psychosis was associated with lower scores on the orientation
      (relative odds ratio, rOR: 0.73; 95% CI: 0.58-0.93; p = 0.011), language (rOR:
      0.64; 95% CI: 0.48-0.86; p = 0.003), and intersecting pentagon (rOR: 0.43; 95%
      CI: 0.20-0.92 p = 0.030) subscales of the MMSE. CONCLUSIONS: In PD, executive
      dysfunction, disorientation, and impaired language comprehension may be
      associated with psychosis. Our findings suggest that the corresponding MMSE
      subscales may be useful in identifying participants with a higher likelihood of
      developing psychosis. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28509349
TI  - Isolation of tissues and preservation of RNA from intact, germinated barley
      grain.
AB  - Isolated barley (Hordeum vulgare L.) aleurone layers have been widely used as a
      model system for studying gene expression and hormonal regulation in germinating
      cereal grains. A serious technological limitation of this approach has been the
      inability to confidently extrapolate conclusions obtained from isolated tissues
      back to the whole grain, where the co-location of several living and non-living
      tissues results in complex tissue-tissue interactions and regulatory pathways
      coordinated across the multiple tissues. Here we have developed methods for
      isolating fragments of aleurone, starchy endosperm, embryo, scutellum, pericarp
      testa, husk and crushed cell layers from germinated grain. An important step in
      the procedure involves the rapid fixation of the intact grain to freeze the
      transcriptional activity of individual tissues while dissection is effected for
      subsequent transcriptomic analyses. The developmental profiles of 19 611 gene
      transcripts were precisely defined in the purified tissues and in whole grain
      during the first 24 h of germination by RNA sequencing. Spatial and temporal
      patterns of transcription were validated against well-defined data on enzyme
      activities in both whole grain and isolated tissues. Transcript profiles of genes
      involved in mitochondrial assembly and function were used to validate the very
      early stages of germination, while the profiles of genes involved in starch and
      cell wall mobilisation matched existing data on activities of corresponding
      enzymes. The data will be broadly applicable for the interrogation of co
      expression and differential expression patterns and for the identification of
      transcription factors that are important in the early stages of grain and seed
      germination.

PMID- 28509350
TI  - High sodium continuous veno-venous hemodialysis with regional citrate
      anticoagulation and online dialysate generation in patients with acute liver
      failure and cerebral edema.
AB  - INTRODUCTION: Acute liver failure is associated with a high mortality rate.
      Induction of plasma hypertonicity with mannitol or hypertonic saline remains the
      cornerstone in the management of resultant cerebral edema. Significant
      disadvantages of this approach include poor or unpredictable control of serum
      sodium concentration and volume expansion, among others. METHODS: We used high
      sodium continuous veno-venous hemodialysis with regional citrate anticoagulation
      and online dialysate generation to accurately control the serum sodium in eleven
      patients with acute liver failure, renal failure, and cerebral edema. We used a
      Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60
      ml/minute and dialysate flow of 400 ml/minute. Our previously published protocol
      results in complete removal of infused citrate by the dialyzer. On-line clearance
      calculations were used to model the time required to reach the target serum
      sodium. FINDINGS: All patients achieved serum sodium within 2 mEq/L of target
      without fluctuations or rebound. Nine patients survived without requiring liver
      transplantation and two died despite reaching the prescribed serum sodium target.
      We did not encounter any citrate toxicity. DISCUSSION: We describe a novel
      approach for delivering continuous osmotherapy to patients with acute liver
      failure, renal failure, and cerebral edema. In comparison to standard therapy,
      the described modality enables precise titration of serum sodium without
      undesirable fluctuations in extracellular fluid volume. A particular advantage is
      zero delivery of citrate to this vulnerable group of patients with acute liver
      failure.

PMID- 28509352
TI  - Convergent mechanisms favor fast amyloid formation in two lambda 6a Ig light
      chain mutants.
AB  - Extracellular deposition as amyloids of immunoglobulin light chains causes light
      chain amyloidosis. Among the light chain families, lambda 6a is one of the most
      frequent in light chain amyloidosis patients. Its germline protein, 6aJL2, and
      point mutants, R24G and P7S, are good models to study fibrillogenesis, because
      their stability and fibril formation characteristics have been described. Both
      mutations make the germline protein unstable and speed up its ability to
      aggregate. To date, there is no molecular mechanism that explains how these
      differences in amyloidogenesis can arise from a single mutation. To look into the
      structural and dynamical differences in the native state of these proteins, we
      carried out molecular dynamics simulations at room temperature. Despite the
      structural similarity of the germline protein and the mutants, we found
      differences in their dynamical signatures that explain the mutants' increased
      tendency to form amyloids. The contact network alterations caused by the
      mutations, though different, converge in affecting two anti-aggregation motifs
      present in light chain variable domains, suggesting a different starting point
      for aggregation in lambda chains compared to kappa chains.

PMID- 28509351
TI  - A transcriptome-based assessment of the astrocytic dystrophin-associated complex
      in the developing human brain.
AB  - Astrocytes play a critical role in regulating the interface between the cerebral
      vasculature and the central nervous system. Contributing to this is the
      astrocytic endfoot domain, a specialized structure that ensheathes the entirety
      of the vasculature and mediates signaling between endothelial cells, pericytes,
      and neurons. The astrocytic endfoot has been implicated as a critical element of
      the glymphatic pathway, and changes in protein expression profiles in this
      cellular domain are linked to Alzheimer's disease pathology. Despite this, basic
      physiological properties of this structure remain poorly understood including the
      developmental timing of its formation, and the protein components that localize
      there to mediate its functions. Here we use human transcriptome data from male
      and female subjects across several developmental stages and brain regions to
      characterize the gene expression profile of the dystrophin-associated complex
      (DAC), a known structural component of the astrocytic endfoot that supports
      perivascular localization of the astroglial water channel aquaporin-4.
      Transcriptomic profiling is also used to define genes exhibiting parallel
      expression profiles to DAC elements, generating a pool of candidate genes that
      encode gene products that may contribute to the physiological function of the
      perivascular astrocytic endfoot domain. We found that several genes encoding
      transporter proteins are transcriptionally associated with DAC genes.

PMID- 28509354
TI  - Single disease entity for both chromosomal instable subtype gastric
      adenocarcinoma and esophageal adenocarcinoma.
AB  - Gastric cardiac carcinoma (GCC) was and is considered as a part of esophageal
      adenocarcinoma (EAC) and staged with the rules for EAC. This may change. Recent
      comprehensive integrated genomic investigations on gastric and esophageal
      carcinomas discovered similar chromosomal instability profiles in these two
      groups of carcinomas with a gradual increasing gradient from the lowest
      percentage in the distal gastric antrum to a high level in the proximal gastric
      cardia, and to the peak of almost 100% in EAC. Therefore, most GCCs and EAC share
      similar chromosomal instable features of gastric carcinoma and should be grouped
      as a single disease entity because EAC may be the proximal extension of
      chromosomal instable GCCs. This breakthrough discovery in genomic characteristics
      of GCC and EAC would dramatically change the strategy on how patients should be
      appropriately managed clinically and also greatly help future investigation on
      detailed molecular pathogenetic mechanisms of GCC, leading to cure this fatal
      cancer.

PMID- 28509353
TI  - Engineering heat tolerance in potato by temperature-dependent expression of a
      specific allele of HEAT-SHOCK COGNATE 70.
AB  - For many commercial potato cultivars, tuber yield is optimal at average daytime
      temperatures in the range of 14-22  degrees C. Further rises in ambient
      temperature can reduce or completely inhibit potato tuber production, with
      damaging consequences for both producer and consumer. The aim of this study was
      to use a genetic screen based on a model tuberization assay to identify
      quantitative trait loci (QTL) associated with enhanced tuber yield. A candidate
      gene encoding HSc70 was identified within one of the three QTL intervals
      associated with elevated yield in a Phureja-Tuberosum hybrid diploid potato
      population (06H1). A particular HSc70 allelic variant was linked to elevated
      yield in the 06H1 progeny. Expression of this allelic variant was much higher
      than other alleles, particularly on exposure to moderately elevated temperature.
      Transient expression of this allele in Nicotiana benthamiana resulted in
      significantly enhanced tolerance to elevated temperature. An TA repeat element
      was present in the promoter of this allele, but not in other HSc70 alleles
      identified in the population. Expression of the HSc70 allelic variant under its
      native promoter in the potato cultivar Desiree resulted in enhanced HSc70
      expression at elevated temperature. This was reflected in greater tolerance to
      heat stress as determined by improved yield under moderately elevated temperature
      in a model nodal cutting tuberization system and in plants grown from stem
      cuttings. Our results identify HSc70 expression level as a significant factor
      influencing yield stability under moderately elevated temperature and identify
      specific allelic variants of HSc70 for the induction of thermotolerance via
      conventional introgression or molecular breeding approaches.

PMID- 28509355
TI  - Lon protease modulates virulence traits in Erwinia amylovora by direct monitoring
      of major regulators and indirectly through the Rcs and Gac-Csr regulatory
      systems.
AB  - Lon, an ATP-dependent protease in bacteria, influences diverse cellular processes
      by degrading damaged, misfolded and short-lived regulatory proteins. In this
      study, we characterized the effects of lon mutation and determined the molecular
      mechanisms underlying Lon-mediated virulence regulation in Erwinia amylovora, an
      enterobacterial pathogen of apple. Erwinia amylovora depends on the type III
      secretion system (T3SS) and the exopolysaccharide (EPS) amylovoran to cause
      disease. Our results showed that mutation of the lon gene led to the
      overproduction of amylovoran, increased T3SS gene expression and the non-motile
      phenotype. Western blot analyses showed that mutation in lon directly affected
      the accumulation and stability of HrpS/HrpA and RcsA. Mutation in lon also
      indirectly influenced the expression of flhD, hrpS and csrB through the
      accumulation of the RcsA/RcsB proteins, which bind to the promoter of these
      genes. In addition, lon expression is under the control of CsrA, possibly at both
      the transcriptional and post-transcriptional levels. Although mutation in csrA
      abolished both T3SS and amylovoran production, deletion of the lon gene in the
      csrA mutant only rescued amylovoran production, but not T3SS. These results
      suggest that CsrA might positively control both T3SS and amylovoran production
      partly by suppressing Lon, whereas CsrA may also play a critical role in T3SS by
      affecting unknown targets.

PMID- 28509356
TI  - Assessments of pain in children and adolescents with cerebral palsy: a
      retrospective population-based registry study.
AB  - AIM: To explore pain screening in CPUP, a follow-up surveillance programme for
      people with cerebral palsy (CP), specifically to describe reported pain
      prevalence, localizations, patterns of distribution; to compare with studies
      using psychometrically sound assessment instruments; and to assess agreement
      between pain documented in CPUP and medical records. METHOD: Registry study of a
      population with CP, born 1993 to 2008, living in Skane, Sweden in 2013.
      Descriptive data, cross-tabulations, and chi-square tests to characterize and
      compare the study groups. Kappa analysis to test the concordance between register
      and medical record reports on pain. RESULTS: Pain was reported by 185 out of 497
      children (37%; females 40%, males 35%). Level V in both Gross Motor Function
      Classification System (GMFCS) and Manual Ability Classification System (MACS) was
      associated with highest prevalence of pain (50% and 54%), and level I with lowest
      prevalence of pain (30% and 32%). Pain was most frequent in dyskinetic CP (46%)
      and least frequent in unilateral spastic CP (33%). Feet and knees were the
      dominant localizations. Fair-moderate agreement (kappa 0.37, prevalence-adjusted
      bias-adjusted kappa [PABAK] 0.44) was found between documented pain in CPUP and
      medical records, although more seldom recognized in medical records.
      INTERPRETATION: The distribution of pain between CP subtypes, functional levels,
      sex, and age in CPUP is concordant with previous population-based studies,
      indicating the validity of the CPUP pain screening. Despite this, further
      clinical evaluation with extended pain assessments and pain management were
      largely neglected in children reporting chronic pain.

PMID- 28509357
TI  - Characterization of microbial mixtures by mass spectrometry.
AB  - MS applications in microbiology have increased significantly in the past 10
      years, due in part to the proliferation of regulator-approved commercial MALDI MS
      platforms for rapid identification of clinical infections. In parallel, with the
      expansion of MS technologies in the "omics" fields, novel MS-based research
      efforts to characterize organismal as well as environmental microbiomes have
      emerged. Successful characterization of microorganisms found in complex mixtures
      of other organisms remains a major challenge for researchers and clinicians
      alike. Here, we review recent MS advances toward addressing that challenge. These
      include sample preparation methods and protocols, and established, for example,
      MALDI, as well as newer, for example, atmospheric pressure ionization (API)
      techniques. MALDI mass spectra of intact cells contain predominantly information
      on the highly expressed house-keeping proteins used as biomarkers. The API
      methods are applicable for small biomolecule analysis, for example, phospholipids
      and lipopeptides, and facilitate species differentiation. MS hardware and
      techniques, for example, tandem MS, including diverse ion source/mass analyzer
      combinations are discussed. Relevant examples for microbial mixture
      characterization utilizing these combinations are provided. Chemometrics and
      bioinformatics methods and algorithms, including those applied to large scale MS
      data acquisition in microbial metaproteomics and MS imaging of biofilms, are
      highlighted. Select MS applications for polymicrobial culture analysis in
      environmental and clinical microbiology are reviewed as well.

PMID- 28509358
TI  - Beware of the predatory science journal: A potential threat to the integrity of
      medical research.
AB  - The issue of predatory journals has become increasingly more prevalent over the
      past decade, as the open-access model of publishing has gained prominence.
      Although the open-access model is well intentioned to increase accessibility of
      biomedical research, it is vulnerable to exploitation by those looking to corrupt
      medical academia and circumvent ethics and research standards. Predatory journals
      will achieve publication by either soliciting unsuspecting researchers who have
      legitimate research but fall victim to these predators or researchers looking to
      quickly publish their research without a thorough review process. Some features
      of predatory journals are a quick non-peer-review process, falsely listing or
      exaggerating the credibility of editorial board members, and either lack of or
      falsification of institutional affiliations and database listings. These
      predatory journals are a serious threat to the integrity of medical research, as
      they will infect the available literature with unsubstantiated articles, and
      allow low-quality research. A number of steps can be taken to prevent the spread
      and increase awareness of predatory publishers, and these must be done to
      maintain the integrity of medical academia. Clin. Anat. 30:767-773, 2017. (c)
      2017Wiley Periodicals, Inc.

PMID- 28509359
TI  - The DNA translocase RAD5A acts independently of the other main DNA repair
      pathways, and requires both its ATPase and RING domain for activity in
      Arabidopsis thaliana.
AB  - Multiple pathways exist to repair DNA damage induced by methylating and
      crosslinking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the
      functional homolog of budding yeast Rad5 that is required for the error-free
      branch of post-replicative repair, plays a surprisingly prominent role in the
      repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase
      domain and the ubiquitination function of the RING domain of the Arabidopsis
      protein are essential for the cellular response to different forms of DNA damage.
      To define the exact role of RAD5A within the complex network of DNA repair
      pathways, we crossed the rad5a mutant line with mutants of different known repair
      factors of Arabidopsis. We had previously shown that RAD5A acts independently of
      two main pathways of replication-associated DNA repair defined by the helicase
      RECQ4A and the endonuclease MUS81. The enhanced sensitivity of all double mutants
      tested in this study indicates that the repair of damaged DNA by RAD5A also
      occurs independently of nucleotide excision repair (AtRAD1), single-strand break
      repair (AtPARP1), as well as microhomology-mediated double-strand break repair
      (AtTEB). Moreover, RAD5A can partially complement for a deficient AtATM-mediated
      DNA damage response in plants, as the double mutant shows phenotypic growth
      defects.

PMID- 28509360
TI  - Supramolecular Assembly Mediated by Metal Ions in Aqueous Solution and Its
      Application in Their Analysis.
AB  - A water-soluble fluorescent sensor based on the interaction of twisted
      cucurbit[14]uril (tQ[14]) and thiazole orange (TO) in aqueous solution was
      developed. Formation of the tQ[14]/TO complex gives rise to stronger fluorescence
      in both neutral and acidic aqueous solutions compared with that of free TO.
      Further experiments on the interaction of the tQ[14]/TO complex with metal ions
      revealed that, from a series of nineteen selected common metal ions, 1) only Hg2+
      can lead to fluorescence enhancement and then quenching of the tQ[14]/TO (2:1)
      complex in neutral aqueous solution; 2) only Ba2+ can induce fluorescence
      quenching of the tQ[14]/TO (2:1) complex in aqueous HCl solution (pH 2);
      furthermore, the tQ[14]/TO/Ba2+ systems exhibit reversible changes in fluorescent
      intensity on successively adding SO42- and Ba2+ ; and 3) only Ba2+ or Pb2+ can
      induce fluorescence quenching of the tQ[14]/TO (15:1) complex in aqueous HCl
      solution (pH 2). Thus, the tQ[14]/TO complex can act as a supramolecular
      fluorescence-based sensor for the determination of Hg2+ , Ba2+ , and Pb2+ ions.

PMID- 28509361
TI  - Prevalence of dental developmental anomalies of permanent teeth in children and
      their influence on esthetics.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of dental
      developmental anomalies in permanent teeth and their influence on esthetics.
      MATERIALS AND METHODS: The records of 473 subjects, which comprised of
      orthopantomograms, clinical examination, and anamnestic data, were explored for
      dental developmental anomalies. Subjects with dental anomalies completed the
      modified questionnaire. Data on reasons for seeking the treatment as well as
      factors affecting the patients' satisfaction were collected. The data were
      processed using the Chi-square test. RESULTS: It was found that 79 subjects
      (16.7%) had at least 1 dental developmental anomaly. The most common anomalies
      were hypodontia (7.2%), followed by talon cusps (3.4%), and microdontia (2.5%).
      Hypodontia, microdontia, and talon cusps were found more prevalent in females
      than males, whereas hyperdontia and macrodontia were more common in males. The
      reason for dissatisfaction with their smile in most cases was due to missing
      teeth or spacing between anterior teeth (excess space 2.9 mm +/- 1.1 mm),
      followed by crowding of anterior teeth (lack of space 3.1 mm +/- 0.8mm),
      difficulty maintaining oral hygiene and midline asymmetry (1.8 mm +/- 0.9 mm).
      All subjects were treated using a fixed orthodontic appliance and 30 (37.9%) of
      them had additional dental specialists included to achieve good esthetics and
      function. Overall, 92.4% of subjects were satisfied with their resulting
      appearance after treatment. CONCLUSIONS: Dental developmental anomalies are
      clinically evident abnormalities. They may be the cause of various dental
      problems and can influence esthetics and the development of orthodontic problems.
      CLINICAL SIGNIFICANCE: This paper evaluates the distribution of dental
      developmental anomalies and their influence on esthetics and function. Careful
      observation and appropriate investigation are required to diagnose the condition
      and institute treatment. The therapeutic approach to some dental anomalies should
      be interdisciplinary.

PMID- 28509363
TI  - Ni-Fe Nitride Nanoplates on Nitrogen-Doped Graphene as a Synergistic Catalyst for
      Reversible Oxygen Evolution Reaction and Rechargeable Zn-Air Battery.
AB  - Obtaining bifunctional electrocatalysts with high activity for the oxygen
      evolution reaction (OER) and oxygen reduction reaction (ORR) is a main hurdle in
      the application of rechargeable metal-air batteries. Earth-abundant 3d transition
      metal-based catalysts have been developed for the OER and ORR; however, most of
      these are based on oxides, whose insulating nature strongly restricts their
      catalytic performance. This study describes a metallic Ni-Fe nitride/nitrogen
      doped graphene hybrid in which 2D Ni-Fe nitride nanoplates are strongly coupled
      with the graphene support. Electronic structure of the Ni-Fe nitride is changed
      by hybridizing with the nitrogen-doped graphene. The unique heterostructure of
      this hybrid catalyst results in very high OER activity with the lowest onset
      overpotential (150 mV) reported, and good ORR activity comparable to that for
      commercial Pt/C. The high activity and durability of this bifunctional catalyst
      are also confirmed in rechargeable zinc-air batteries that are stable for 180
      cycles with an overall overpotential of only 0.77 V at 10 mA-2 .

PMID- 28509362
TI  - Developing Polyamine-Based Peptide Amphiphiles with Tunable Morphology and
      Physicochemical Properties.
AB  - The ability to tune supramolecular properties such as size, morphology, or
      metabolic stability is of paramount importance in the field of supramolecular
      chemistry. Peptide amphiphiles (PAs) are a family of functional self-assembling
      biomaterials that have garnered widespread attention due to their broad
      applicability in medicine. PAs are generally comprised of an amino acid sequence
      connected to lipid tail(s) allowing them to self-assemble into supramolecular
      structures with diverse morphologies. Herein, this study describes the synthesis
      of a new class of polyamine-based "hybrid" PAs (PPAs) as novel self-assembling
      systems. The described molecules possess diverse polyamine head groups with the
      goal of tuning physicochemical properties. The findings indicate that small
      changes in the polyamine head groups result in altered PPA morphologies
      (nanofibers, micelles, nanoworms). The PPAs present a wide range of
      physicochemical characteristics, show superior resistance to aggregation, a
      diverse metabolic profile, and varied assembling kinetics. Most of the PPAs do
      not show toxicity in the human cells lines evaluated. The PPAs described herein
      hold promising potential as a safe and nontoxic option for drug delivery,
      targeting, and tissue engineering applications.

PMID- 28509364
TI  - How do caregivers understand and respond to unsettled infant behaviour in
      Vietnam? A qualitative study.
AB  - BACKGROUND: Unsettled infant behaviours are a common source of concern for new
      parents and have been associated with perinatal common mental disorders amongst
      women in high-income settings. There is little evidence about how unsettled
      infant behaviours are understood and managed in low and lower-middle income
      countries. This study aimed to describe caregivers' understandings of, and
      responses to, unsettled infant behaviours in Vietnam and their family caregiving
      contexts. METHODS: Women who were mothers of infants aged 0-6 months were
      purposively recruited from two sites in Thua Thien Hue Province, Vietnam (one
      urban and one rural). An additional group of women who were grandmothers were
      recruited by snowball sampling. Data were collected in semi-structured interviews
      about demographic information, infant feeding practices, descriptions of infant
      crying episodes, beliefs about why infants cry, settling strategies, infant
      sleeping arrangements and sources of advice on infant care. Translated interview
      transcripts were analysed thematically. RESULTS: Twenty-four interviews were
      undertaken (21 with mothers and 3 with grandmothers). Five major themes emerged
      from the data after analysis: infant settling techniques, sources of information
      on unsettled infant behaviour, understandings of the causes of infant crying, the
      emotional responses of caregivers and the intergenerational household context.
      Infants were commonly cared for by people from multiple generations, particularly
      during the day. Infant settling was characterized by attending to infants
      immediately, breastfeeding and bed-sharing with parents during the night. Most
      mothers received advice on caregiving from family members. Infant crying was
      attributed to hunger and loneliness, as well as traditional beliefs that the
      infant was being upset by 'ghosts' or becoming 'hot'. Women described feeling
      anxious, frustrated and helpless in relation to unsettled behaviours amongst
      their infants. CONCLUSIONS: Educational interventions on interpreting infant
      cues, infant sleep requirements and bed sharing may be appropriate in Vietnam if
      multiple generations are included and traditional beliefs about infant crying are
      addressed.

PMID- 28509365
TI  - The degree of satisfaction of in-hospital medical patients with nursing care and
      predictors of dissatisfaction: findings from a secondary analysis.
AB  - BACKGROUND: Patient satisfaction with nursing care (NC) is an important predictor
      of overall satisfaction with the hospital experience. However, the concept of
      patient satisfaction has been criticised both at the theoretical and at the
      methodological levels, and more attention on patient dissatisfaction has been
      called for with the aim of identifying strategies to improve the quality of care.
      AIMS: To describe dissatisfaction with NC as perceived by acute medical patients
      and identify predictors. DESIGN AND METHODS: A secondary analysis of longitudinal
      data involving 12 Italian medical units was performed. A consecutive sample of
      1016 patients >=65 years (2012-2013) was included, and their satisfaction with NC
      was assessed, administering the Italian version of the Patient Satisfaction Scale
      (PSS) at the day of discharge. The scale was based on 11 items evaluated on a
      four-point Likert scale (score ranging from 11 - very dissatisfied to 44 - very
      satisfied). Patients were defined as 'satisfied with NC' when the score was >=33,
      whereas they were considered as 'dissatisfied with NC' when the score was <33. A
      logistic regression analysis was performed to identify the predictors of patient
      dissatisfaction with NC. RESULTS: There were 788 (77.6%) patients satisfied (>=33
      at the PSS) and 228 (22.4%) dissatisfied with NC (<33). The risk of
      dissatisfaction was likely to be higher in female patients (RR 1.883, 95% CI
      1.359-2.609), in those who developed pressure sores during the in-hospital stay
      (RR 1.555, 95% CI 1.021-2.368), who received NC with high skill mix (RR 1.072,
      95% CI 1.034-1.111) and those who were admitted to a large hospital (RR 1.001,
      95% CI 1.001-1.002). In contrast, increased age (RR 0.987, 95% CI 0.975-0.998),
      increased amount of care offered by Registered Nurses (RR 0.984, 95% CI 0.974
      0.994), a higher proportion of baccalaureate nurses on staff (RR 0.975, 95% CI
      0.958-0.993) and being admitted to a teaching hospital (RR 0.497, 95% CI 0.130
      0.910) all decreased the likelihood of being dissatisfied with NC. CONCLUSIONS:
      Dissatisfaction with NC was affected by individual, NC and hospital variables,
      such as the amount of staff resources, nurses education and skill mix. The
      findings emerged may inform clinicians, managers and policymakers regarding
      strategies that should be designed and implemented to prevent patient
      dissatisfaction.

PMID- 28509366
TI  - On the quality of adjustment to retirement: The longitudinal role of personality
      traits and generativity.
AB  - OBJECTIVE: Although psychological factors have been explored in relation to other
      life transitions, their influence on retirement adjustment quality has been
      largely overlooked. This study assessed the contribution of personality traits
      and generativity before retirement in the prediction of hedonic and eudaimonic
      well-being at two temporal points after retirement. METHOD: This article analyzes
      data from the Midlife in the United States (MIDUS) longitudinal sample.
      Specifically, it uses a subsample of people who were not retired at Time 1, but
      were 9 years after at Time 2 (n = 548) and 18 years after at Time 3 (n = 351).
      RESULTS: After controlling both for initial values on hedonic and eudaimonic well
      being and for the effects of personal attributes and resources, higher scores on
      Extraversion at Time 1 significantly predicted hedonic well-being at Time 2,
      whereas lower scores on Neuroticism and higher scores on generativity at Time 1
      significantly predicted eudaimonic well-being at Time 2. Neuroticism and
      generative concern at Time 1 remained significant in the prediction of eudaimonic
      well-being at Time 3. CONCLUSIONS: The study shows that personality traits and
      generative concern at midlife explain a meaningful part of the variation in
      individuals' quality of subsequent retirement adjustment.

PMID- 28509368
TI  - Shining the spotlight on education.

PMID- 28509367
TI  - Measuring change in perceived well-being of family caregivers: validation of the
      Spanish version of the Perceived Change Index (PCI-S) in Chilean dementia
      caregivers.
AB  - OBJECTIVE: Few instruments evaluate family caregiver perceptions of challenges
      caring for persons with dementia and improvement or worsening in these areas. To
      address this measurement gap, we examine psychometric properties of a Spanish
      version of the 13-item Perceived Change Index (PCI-S), originally validated with
      English-speaking caregivers. METHODS: Cross-sectional study with 94 caregivers of
      persons with mild to moderate dementia in Chile. Interviews included caregiver
      demographics, burden, health perception, distress with behaviours, dementia
      severity, behavioural symptoms and functionality. RESULTS: Caregiver mean age was
      55.9 (SD +/- 14.14) years and mean years caregiving was 3 (SD +/- 2.60). The
      scale had strong internal consistency (Cronbach alpha = 0.94), and inter-observer
      consistency (CCI = 0.99; 95% CI = 0.95-0.99). Two factors were identified:
      Management skills (alpha = 0.89), and somatic well-being and affects (alpha =
      0.92), explaining 63% of scale variance. Significant associations supporting
      convergent validity were observed for PCI-S and subscales with caregiver burden
      (p < 0.01), health perceptions (p < 0.01), depressive symptoms (p < 0.01) and
      distress with behaviours (p < 0.01); and in persons with dementia, functionality
      (p < 0.05), dementia severity (p < 0.05) and behavioural symptoms (p < 0.01) in
      expected directions. In logistic regression models, perceived worsening (PCI-S
      and subscale scores) was associated with more behavioural symptoms (OR = 1.07;
      95% CI = 1.03-1.15) and caregiver burden (OR = 1.48; 95% CI = 1.18-1.86); whereas
      perceived improvement was associated with higher physical functioning (OR = 0.95;
      95% CI = 0.91-0.99) in persons with dementia. PCI-S scores were not associated
      with socio-demographic characteristics reflecting divergent validity.
      CONCLUSIONS: Spanish version of the 13-item Perceived Change Index and its two
      factor solution is a valid and reliable measure with clinical utility to detect
      improvement or worsening in caregivers concerning daily care challenges.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28509370
TI  - Use of mushroom tyrosinase to introduce michaelis-menten enzyme kinetics to
      biochemistry students.
AB  - An inexpensive enzyme kinetics laboratory exercise for undergraduate biochemistry
      students is described utilizing tyrosinase from white button mushrooms. The
      exercise can be completed in one or two three-hour lab sessions. The optimal
      amounts of enzyme, substrate (catechol), and inhibitor (kojic acid) are first
      determined, and then kinetic data is collected in the absence and presence of the
      inhibitor. A Microsoft Excel template is used to plot the data and to fit the
      Michaelis-Menten equation to the data to determine the kinetic parameters Vmax
      and Km . The exercise is designed to clarify and reinforce concepts covered in an
      accompanying biochemistry lecture course. It has been used with positive results
      in an upper-level biochemistry laboratory course for junior/senior students
      majoring in chemistry or biology. (c) 2016 by The International Union of
      Biochemistry and Molecular Biology, 45(3):270-276, 2017.

PMID- 28509372
TI  - Differential expression of microRNA related to irritable bowel syndrome in a
      rabbit model.
AB  - OBJECTIVE: This study aimed to evaluate the differential expressions of microRNAs
      (miRNAs) in white hair black eye (WHBE) rabbits of irritable bowel syndrome
      (IBS). METHODS: WHBE and Japanese white (JW) rabbits were divided into the
      control and IBS groups. The IBS groups were exposed to moist heat, stress and low
      dose laxatives. Their intestinal movement rate was measured. Blood samples were
      taken to detect serum 5-hydroxytryptamine (5-HT) and dopamine levels and colonic
      tissues were obtained to detect c-Fos expression by immunohistochemistry. Deep
      sequencing technology was used to obtain miRNA sequences in the intestinal
      tissues of WHBE and JW control groups. Expressions of 14 miRNAs were measured by
      real-time polymerase chain reaction in both the control and the IBS model groups.
      RESULTS: Serum 5-HT and dopamine levels, intestinal movement rate and c-Fos
      expressions in the WHBE rabbits were significantly increased compared with the
      control group. MiR-29a-3p, miR-24-3p, miR-221-3p, let-7f-5p, let-7g-5p, let-7i
      5p, miR-192-5p, miR-126-3p and miR-130b-3p expressions in WHBE IBS rabbits at day
      14 were significantly higher than those in the control group while miR-324-3p and
      miR-132 were downregulated. MiR-29a-3p, let-7i-5p, miR-192-5p and miR-126-3p were
      significantly upregulated only in JW IBS rabbits at day 14 and miR-324-3p, miR
      223-3p and miR-132 were significantly downregulated in JW IBS group. MiR-24-3p,
      miR-221-3p, let-7f-5p, miR-126-3p and miR-130b-3p expressions in WHBE IBS rabbits
      were higher than that in JW IBS rabbits. CONCLUSIONS: Twelve miRNAs were
      differentially expressed in IBS rabbits. Five are specific in WHBE IBS rabbits,
      suggesting that they play a role in increased sensitivity to IBS.

PMID- 28509371
TI  - Quantitative Assessment of Sialo-Glycoproteins and N-Glycans during
      Cardiomyogenic Differentiation of Human Induced Pluripotent Stem Cells.
AB  - Human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC CMs) may be
      used in regenerative medicine for individualized tissue transplants in the
      future. For application in patients, the generated CMs have to be highly pure and
      well characterized. In order to overcome the prevalent scarcity of CM-specific
      markers, we quantitatively assessed cell-surface-exposed sialo-glycoproteins and
      N-glycans of hiPSCs, CM progenitors, and CMs. Applying a combination of metabolic
      labeling and specific sialo-glycoprotein capture, we could highly enrich and
      quantify membrane proteins during cardiomyogenic differentiation. Among them we
      identified a number of novel, putative biomarkers for hiPSC CMs. Analysis of the
      N-glycome by capillary gel electrophoresis revealed three novel structures
      comprising beta1,3-linked galactose, alpha2,6-linked sialic acid and complex
      fucosylation; these were highly specific for hiPSCs. Bisecting GlcNAc structures
      strongly increased during differentiation, and we propose that they are
      characteristic of early, immature CMs.

PMID- 28509373
TI  - BK viremia surveillance and outcomes in simultaneous pancreas-kidney transplant
      recipients.
AB  - BACKGROUND: While screening for asymptomatic BK viremia (BKV) has been well
      studied in isolated kidney transplant recipients, there is a paucity of published
      outcomes in simultaneous pancreas-kidney (SPK) transplant recipients who
      underwent BKV screening followed by pre-emptive reduction in immunosuppression.
      METHODS: This is a single-center, retrospective review of 31 consecutive SPK
      recipients who were transplanted over a 5-year period following the initiation of
      a serum BKV screening protocol. RESULTS: BK viremia developed in 11 (35.5%)
      patients, and all patients achieved complete viral clearance following reduction
      in immunosuppression. Two patients (6.5%) developed BK virus nephropathy, but
      both had preserved allograft function. One patient developed mild rejection of
      the kidney allograft following clearance of BKV, and two patients developed mild
      rejection of the pancreas allograft after reduction in immunosuppression, but
      there were no kidney or pancreas allograft losses due to rejection. The
      development of BK viremia did not impact overall patient survival or kidney and
      pancreas allograft survival. CONCLUSION: Screening asymptomatic SPK recipients
      for BKV followed by reduction in maintenance immunosuppression appears to be an
      effective strategy to prevent kidney allograft dysfunction and graft loss due to
      BK virus nephropathy, without compromising pancreas allograft outcomes.

PMID- 28509374
TI  - The STENOFOLIA gene from Medicago alters leaf width, flowering time and
      chlorophyll content in transgenic wheat.
AB  - Molecular genetic analyses revealed that the WUSCHEL-related homeobox (WOX) gene
      superfamily regulates several programs in plant development. Many different
      mechanisms are reported to underlie these alterations. The WOX family member
      STENOFOLIA (STF) is involved in leaf expansion in the eudicot Medicago
      truncutula. Here, we report that when this gene was ectopically expressed in a
      locally adapted hard red winter wheat cultivar (Triticum aestivum), the
      transgenic plants showed not only widened leaves but also accelerated flowering
      and increased chlorophyll content. These desirable traits were stably inherited
      in the progeny plants. STF binds to wheat genes that have the (GA)n /(CT)n DNA
      cis element, regardless of sequences flanking the DNA repeats, suggesting a
      mechanism for its pleiotropic effects. However, the amino acids between position
      91 and 262 in the STF protein that were found to bind with the (GA)n motif have
      no conserved domain with any other GAGA-binding proteins in animals or plants. We
      also found that STF interacted with a variety of proteins in wheat in yeast 2
      hybrid assays. We conclude that the eudicot STF gene binds to (GA)n /(CT)n DNA
      elements and can be used to regulate leaf width, flowering time and chlorophyll
      content in monocot wheat.

PMID- 28509375
TI  - Chronic nicotine-induced changes in gene expression of delta and kappa-opioid
      receptors and their endogenous ligands in the mesocorticolimbic system of the
      rat.
AB  - Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous
      ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are
      proposed as important mediators of nicotine reward. This study investigated the
      regulatory effect of chronic nicotine treatment on the gene expression of DOR,
      KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were
      injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for
      6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing
      coincides with increased dopamine release in the mesocorticolimbic system. mRNA
      levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA),
      amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal
      cortex were measured by quantitative real-time PCR. Our results showed that
      nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG
      at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely,
      PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4
      mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine.
      Nicotine did not regulate PENK mRNA in any brain region studied.

PMID- 28509376
TI  - Adverse Childhood Experiences (ACEs), Stress and Mental Health in College
      Students.
AB  - The goal of this short-term longitudinal study was to examine whether adverse
      childhood experiences (ACEs) could be used to identify college students at risk
      for mental health problems and whether current level of stress mediates the
      relationship between ACEs and mental health. Data on ACEs and mental health
      (depression, anxiety and suicidality) were collected at the beginning of the
      semester, and data on current stressors and mental health were collected toward
      the end of the semester (n = 239). Findings indicated that ACEs predicted
      worsening of mental health over the course of a semester and suggested current
      number of stressors as a mediator of the relationship between ACEs and mental
      health. Results suggest that screening for ACEs might be useful to identify
      students at high risk for deterioration in mental health. Results further suggest
      that stress-related interventions would be beneficial for students with high
      levels of ACEs and point to the need for more research and strategies to increase
      help-seeking in college students.

PMID- 28509377
TI  - H3.1 K36M mutation in a congenital-onset soft tissue neoplasm.
AB  - We describe a patient who presented with a congenital soft tissue lesion
      initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the
      mass demonstrated malignant progression leading to death at 20 months of age.
      Biological progression to malignancy is not known to occur in fibromatosis, and
      fibrosarcoma is not known to progress from a benign lesion. Whole-exome
      sequencing of the tumor identified a driver mutation in histone H3.1 at lysine
      (K)36. Our findings support the link between oncohistones and infantile soft
      tissue tumors and provide additional evidence for the oncogenic effects of p.K36M
      in H3 variants.

PMID- 28509378
TI  - Evaluation of the skin phototoxicity and photosensitivity of honeybee venom.
AB  - OBJECTIVE: Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic
      ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects.
      The aim of this study was to assess the skin safety of BV. METHODS: For this
      purpose, skin phototoxicity and sensitization tests were conducted in healthy
      male Hartley guinea pigs. The animals were divided into three groups (n=5) for
      the phototoxicity test: G1 (negative control), G2 (BV gel treatment), and G3
      (positive control). After specified treatments, the animals were irradiated with
      ultraviolet A (15 J/cm2 ). The photosensitivity test was also performed in three
      groups: G4 (negative control, n=5), G5 (BV gel treatment, n=10), and G6 (positive
      control, n=5). RESULTS: Erythema and edema were observed after 24, 48, and 72
      hours in the positive control group, but not in the negative control and BV gel
      groups. Application of BV to the guinea pig skin had no toxic effects on any
      clinical signs, body weight, or mortality. In addition, it did not evoke a skin
      reaction in both either the skin phototoxicity and skin photosensitization tests.
      CONCLUSION: Therefore, it can be concluded that BV has the potential to be
      developed as a drug ingredient for topical uses.

PMID- 28509380
TI  - Amyloid is essential but insufficient for Alzheimer causation: addition of
      subcellular cofactors is required for dementia.
AB  - OBJECTIVE: The aim of this study is to examine the hypotheses stating the
      importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's
      disease (AD). METHODS: Published studies were examined. RESULTS: The importance
      of amyloid in the pathogenesis of AD is well established, yet accepting it as the
      main cause for AD is problematic, because amyloid-centric treatments have
      provided no clinical benefit and about one-third of cognitively normal, older
      persons have cerebral amyloid plaques. Also problematic is the alternative
      hypothesis that, instead of amyloid plaques, it is oligomers of amyloid precursor
      protein that cause AD.Evidence is presented suggesting amyloid/oligomers as
      necessary but insufficient causes of the dementia and that, for dementia to
      develop, requires the addition of cofactors known to be associated with AD. Those
      cofactors include several subcellular processes: mitochondrial impairments; the
      Wnt signaling system; the unfolded protein response; the ubiquitin proteasome
      system; the Notch signaling system; and tau, calcium, and oxidative damage.
      CONCLUSIONS: A modified amyloid/oligomer hypothesis for the pathogenesis of AD is
      that activation of one or more of the aforementioned cofactors creates a burden
      of functional impairments that, in conjunction with amyloid/oligomers, now
      crosses a threshold of dysfunction that results in clinical dementia. Of
      considerable importance, several treatments that might reverse the activation of
      some of the subcellular processes are available, for example, lithium,
      pioglitazone, erythropoietin, and prazosin; they should be given in combination
      in a clinical trial to test their safety and efficacy. (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28509379
TI  - Microbial Eukaryotes that Lack Sterols.
AB  - It is widely held that sterols are key cyclic triterpenoid lipids in eukaryotic
      cell membranes and are synthesized through oxygen-dependent multienzyme pathways.
      However, there are known exceptions-ciliated protozoans, such as Tetrahymena,
      along with diverse low-oxygen-adapted eukaryotes produce, instead of sterols, the
      cyclic triterpenoid lipid tetrahymanol that does not require molecular oxygen for
      its biosynthesis. Here, we report that a number of anaerobic microbial eukaryotes
      (protists) utilize neither sterols nor tetrahymanol in their membranes. The lack
      of detectable sterol-like compounds in their membranes may provide an opportunity
      to reconsider the physiological function of sterols and sterol-like lipids in
      eukaryotes.

PMID- 28509381
TI  - Topography-Guided Control of Local Migratory Behaviors and Protein Expression of
      Cancer Cells.
AB  - In vivo cancer cell migration and invasion are directed by biophysical guidance
      mechanisms such as pre-existing microtracks and basement membrane extracellular
      matrices. Here, this paper reports the correlation of the local migratory
      behavior of cancer cells and the biochemical signal expression using the
      topography that can guide or inhibit cell behaviors. To this end, the local
      apparent migration and the protein expression level are investigated with respect
      to the topographical feature size (flat, nanoline, and microline) and orientation
      (microline, microconcentric, and microradial) with the collectively migrating
      (A431) and individually migrating (MDA-MB-231 and U-87-MG) cancer cells. The
      results show that the migration and the protein expression of focal adhesion
      kinase, rho-associated protein kinase, and extracellular signal-regulated kinase
      are localized in the periphery of cell colony. Furthermore, the inhibition of
      migratory behavior at the periphery recues the protein expression, while the
      guidance of migration enhances the aforementioned protein expression. The results
      may imply the employ of biophysical inhibitory factors can help to control
      invasiveness of cancer cells during the progression state.

PMID- 28509382
TI  - Paratesticular desmoplastic small round cell tumors: A case report and review of
      the literature.
AB  - Desmoplastic small round cell tumor (DSCRT) is a rare malignancy most often seen
      in the abdomen or pelvis of young men. Unfortunately, this disease is usually
      metastatic at diagnosis and has dismal outcomes. We describe a case of isolated
      paratesticular DSCRT in a 14-year-old male successfully treated with surgical
      resection, chemotherapy, and adjuvant radiation, and we present a review of the
      relevant literature. It appears that isolated, paratesticular DSCRTs have a
      markedly better outcome than the classic abdominal or pelvic location. We
      hypothesize that this is due to earlier detection and the relative ease of
      surgical resection.

PMID- 28509383
TI  - Arab-Levantine personality structure: A psycholexical study of modern standard
      Arabic in Lebanon, Syria, Jordan, and the West Bank.
AB  - OBJECTIVE: The debate of whether personality traits are universal or culture
      specific has been informed by psycholexical (or lexical) studies conducted in
      tens of languages and cultures. We contribute to this debate through a series of
      studies in which we investigated personality descriptors in Modern Standard
      Arabic, the variety of Arabic that is presumably common to about 26 countries and
      native to more than 200 million people. METHOD: We identified an appropriate
      source of personality descriptors, extracted them, and systematically reduced
      them to 167 personality traits that are common, are not redundant with each
      other, and are familiar and commonly understood in Lebanon, Syria, Jordan, and
      the West Bank (Palestinian territories). RESULTS: We then analyzed self- and peer
      ratings (N = 806) and identified a six-factor solution comprising Morality (I),
      Conscientiousness (II), Positive Emotionality (III), Dominance (IV),
      Agreeableness/Righteousness (V), and Emotional Stability (VI) without replicating
      an Openness factor. CONCLUSIONS: The factors were narrower or broader variants of
      factors found in the Big Five and HEXACO models. Conceptual and methodological
      considerations may have impacted the factor structure.

PMID- 28509384
TI  - Individual differences in personality change across the adult life span.
AB  - OBJECTIVE: A precise and comprehensive description of personality continuity and
      change across the life span is the bedrock upon which theories of personality
      development are built. Little research has quantified the degree to which
      individuals deviate from mean-level developmental trends. In this study, we
      addressed this gap by examining individual differences in personality trait
      change across the life span. METHOD: Data came from a nationally representative
      sample of 9,636 Dutch participants who provided Big Five self-reports at five
      assessment waves across 7 years. We divided our sample into 14 age groups (ages
      16-84 at initial measurement) and estimated latent growth curve models to
      describe individual differences in personality change across the study period for
      each trait and age group. RESULTS: Across the adult life span, individual
      differences in personality change were small but significant until old age. For
      Openness, Conscientiousness, Extraversion, and Agreeableness, individual
      differences in change were most pronounced in emerging adulthood and decreased
      throughout midlife and old age. For Emotional Stability, individual differences
      in change were relatively consistent across the life span. CONCLUSIONS: These
      results inform theories of life span development and provide future directions
      for research on the causes and conditions of personality change.

PMID- 28509385
TI  - Molecular events leading to death of Leishmania donovani under spermidine
      starvation after hypericin treatment.
AB  - We have previously reported that the hypericin treatment caused spermidine
      starvation and death of Leishmania parasite. Here, we report different molecular
      events under spermidine starvation and potential role of spermidine in processes
      other than redox homeostasis of the parasite. We have analyzed changes in
      expression of several genes by using quantitative gene expression analysis.
      Further, these changes at molecular level were also confirmed by using
      biochemical and cellular studies. Altered expression of several genes involved in
      redox metabolism, hypusine modification of eIF5A, DNA repair pathway and
      autophagy was observed. There was decrease in Sir2RP expression after hypericin
      treatment and this decrease has been found to be associated with induced ROS due
      to hypericin treatment as it has been rescued by either trypanothione or
      spermidine supplementation. Translation initiation in the parasite was decreased
      upon spermidine starvation. We also observed increased AMPK expression upon
      hypericin treatment. The increase in intracellular ATP and NAD+ levels as well as
      decrease in Sir2RP expression of the parasite are cytoprotective mechanism
      towards generated ROS due to hypericin treatment possibly by inducing autophagy
      as indicated by increase in autophagy related gene expression and acridine orange
      staining. However, the autophagy needs to be established using more rigorous
      methodologies.

PMID- 28509386
TI  - Descending pathways to the spinal cord in teleosts in comparison with mammals,
      with special attention to rubrospinal pathways.
AB  - In this article we review descending neural pathways to the spinal cord in
      teleosts, compared with mammals. Descending pathways to the spinal cord are
      crucial in controlling various behaviors in vertebrates. The major difference
      between teleosts and mammals is the lack of corticospinal (or palliospinal)
      tracts. Other descending pathways, which originate from the brain stem, are
      basically identical in teleosts and mammals. This suggests the presence of common
      systems in the spinal motor control by higher order centers. The homologue of
      nucleus ruber remained unclear in teleosts until recently, and this review pays
      special attention to the rubrospinal tract.

PMID- 28509387
TI  - Progranulin increases phagocytosis by retinal pigment epithelial cells in
      culture.
AB  - Retinal pigment epithelium (RPE) cells take part in retinal preservation, such as
      phagocytizing the shed photoreceptor outer segments (POS), every day. The
      incomplete phagocytic function accelerates RPE degeneration and formation of the
      toxic by-product lipofuscin. Excessive lipofuscin accumulation is characteristic
      of various blinding diseases in the human eye. Progranulin is a cysteine-rich
      protein that has multiple biological activities, and it has a high presence in
      the retina. Progranulin has been recognized to be involved in macrophage
      phagocytosis in the brain. The purpose of this study is to determine whether
      progranulin influences phagocytosis by RPE cells. All experiments were performed
      on primary human RPE (hRPE) cells in culture. pHrodo was used to label the
      isolated porcine POS, and quantification of pHrodo fluorescence was used to
      determine the degree of phagocytosis. Western blotting and immunohistochemistry
      of key proteins involved in phagocytosis were used to clarify the mechanism of
      progranulin. Progranulin increased RPE phagocytosis in hydrogen peroxide-treated
      and nontreated RPE cells. The phosphorylated form of Mer tyrosine kinase, which
      is important for POS internalization, was significantly increased in the
      progranulin-exposed cells. This increase was attenuated by SU11274, an inhibitor
      of hepatic growth factor receptor. Under the oxidative stress condition, exposure
      to progranulin led to an approximately twofold increase in integrin alpha-v,
      which is associated with the first step in recognition of POS by RPE cells. These
      results suggest that progranulin could be an effective stimulator for RPE
      phagocytosis and could repair RPE function. (c) 2017 Wiley Periodicals, Inc.

PMID- 28509389
TI  - A Revised Sociogenomic Model of Personality Traits.
AB  - In this article, I seek to update the sociogenomic model of personality traits
      (Roberts & Jackson, 2008). Specifically, I seek to outline a broader and more
      comprehensive theoretical perspective on personality traits than offered in the
      original version of the sociogenomic model of personality traits. First, I review
      the major points of our 2008 article. Second, I update our earlier model mostly
      with insights derived from a deeper reading of evolutionary theoretical systems,
      such as those found in life-history theory and ecological-evolutionary
      developmental biology. In particular, this revision incorporates two evolutionary
      informed systems, labeled pliable and elastic systems, that provide new insights
      into how personality traits develop. Third, I describe some of the implications
      of this new understanding of the biological and evolutionary architecture that
      underlies human phenotypes such as personality traits.

PMID- 28509388
TI  - Proteomic explorations of autism spectrum disorder.
AB  - Proteomics, the large-scale study of protein expression in cells and tissues, is
      a powerful tool to study the biology of clinical conditions and has provided
      significant insights in many experimental systems. Herein, we review the basics
      of proteomic methodology and discuss challenges in using proteomic approaches to
      study autism. Unlike other experimental approaches, such as genomic approaches,
      there have been few large-scale studies of proteins in tissues from persons with
      autism. Most of the proteomic studies on autism used blood or other peripheral
      tissues; few studies used brain tissue. Some studies found dysregulation of
      aspects of the immune system or of aspects of lipid metabolism, but no consistent
      findings were noted. Based on the challenges in using proteomics to study autism,
      we discuss considerations for future studies. Apart from the complex technical
      considerations implicit in any proteomic analysis, key nontechnical matters
      include attention to subject and specimen inclusion/exclusion criteria, having
      adequate sample size to ensure appropriate powering of the study, attention to
      the state of specimens prior to proteomic analysis, and the use of a replicate
      set of specimens, when possible. We conclude by discussing some potentially
      productive uses of proteomics, potentially coupled with other approaches, for
      future autism research including: (1) proteomic analysis of banked human brain
      specimens; (2) proteomic analysis of tissues from animal models of autism; and
      (3) proteomic analysis of induced pluripotent stem cells that are differentiated
      into various types of brain cells and neural organoids. Autism Res 2017, 10: 1460
      1469. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 28509390
TI  - Pilot study of client outcomes from exercise physiology in a youth mental health
      service.
AB  - The aim of this pilot study was to evaluate the utilisation and experience of an
      exercise physiology programme, known as Bod Squad at a youth mental health
      service. Individual sessions were offered in an outpatient setting, while both
      group and individual sessions occurred in an inpatient unit. This pilot study
      used a mixed methodology to collect data from young people who attended Bod
      Squad. A database of exercise physiology records for 47 young people were
      analysed for attendance and physiological indicators. In addition, 7 semi
      structured interviews were conducted with young people to explore their
      experience of Bod Squad. Young people attended a total of 169 sessions during the
      programmes tenure, with an overall mean of 3.6 sessions. Pre-post measures for 10
      young people (who had attended at least 4 sessions) showed modest average
      reductions for body mass index, waist circumference, chest circumference and
      resting heart rate. Five themes emerged from the interviews-(1) My reasons for
      attending, (2) The social aspect, (3) An individualized approach, (4) Outcomes
      from Bod Squad and (5) My experience of the service. All of these themes included
      positive experiences of Bod Squad, which young people perceived as relevant to
      their needs and helpful to their recovery. These findings are congruent with
      previous studies that have concluded that exercise physiology may be an
      effective, acceptable and valued intervention for addressing physical and
      metabolic health issues for young people.

PMID- 28509391
TI  - Common mental disorder including psychotic experiences: Trailblazing a new
      recovery pathway within the Improving Access to Psychological Therapies programme
      in England.
AB  - Psychotic experiences, depressive and anxiety symptoms may be manifestations of a
      latent continuum of common mental distress. The Improving Access to Psychological
      Therapies (IAPT) programme has increased the reach of psychological treatments to
      people with common mental disorders in England. However, psychotic experiences
      are neither measured nor considered in therapy. We aimed to confirm the presence
      of psychotic experiences among IAPT service-users and determine whether these
      experiences are associated with higher depression/anxiety levels and poorer
      recovery. All service-users that attended the Fenland and Peterborough IAPT teams
      in Cambridgeshire between November 16, 2015 and January 29, 2016 participated in
      a service evaluation. In addition to routine mesures, such as the Generalized
      Anxiety Disorder-7 questionnaire (GAD-7) and the Patient Health Questionnaire-9
      (PHQ-9), we introduced a shortened version of the Community Assessment of Psychic
      Experiences (CAPE-P15) to measure psychotic experiences. Classes of individuals
      were identified with latent class analysis. Associations were reported using
      Pearson correlation coefficient. One hundred and seventy-three services-users
      were included, mostly females (N = 133; 76.9%). The mean age was 36.6 (SD =
      13.3). Around 30% likely belonged to a class with psychotic experiences. CAPE-P15
      frequency was significantly correlated to PHQ-9 (r = 0.44; P < .001) and GAD-7 (r
      = 0.32; P < .001). Similarly, CAPE-P15 distress and both PHQ-9 (r = 0.43; P <
      .001) and GAD-7 (r = 0.38; P < .001) were highly correlated. These associations
      were replicated after the initial period of the therapy, indicating poor
      recovery. Some IAPT service-users suffer psychotic experiences. Tailoring
      available evidence-based psychological therapies for these people in IAPT
      settings might trailblaze a new care pathway to improve recovery in this group.

PMID- 28509393
TI  - NmeA, a novel efflux transporter specific for nucleobases and nucleosides,
      contributes to metal resistance in Aspergillus nidulans.
AB  - Through Minos transposon mutagenesis we obtained A. nidulans mutants resistant to
      5-fluorouracil due to insertions into the upstream region of the uncharacterized
      gene nmeA, encoding a Major Facilitator Superfamily (MFS) transporter. Minos
      transpositions increased nmeA transcription, which is otherwise extremely low
      under all conditions tested. To dissect the function of NmeA we used strains
      overexpressing or genetically lacking the nmeA gene. Strains overexpressing NmeA
      are resistant to toxic purine analogues, but also, to cadmium, zinc and borate,
      whereas an isogenic nmeADelta null mutant exhibits increased sensitivity to these
      compounds. We provide direct evidence that nmeA overexpression leads to efflux of
      adenine, xanthine, uric acid and allantoin, the latter two being intermediate
      metabolites of purine catabolism that are toxic when accumulated cytoplasmically
      due to relevant genetic lesions. By using a functional GFP-tagged version we show
      that NmeA is a plasma membrane transporter. Homology modeling and docking
      approaches identified a single purine binding site and a tentative substrate
      translocation trajectory in NmeA. Orthologues of NmeA are present in all
      Aspergilli and other Eurotiomycetes, but are absent from other fungi or non
      fungal organisms. NmeA is thus the founding member of a new class of transporters
      essential for fungal success under specific toxic conditions.

PMID- 28509394
TI  - Room-Temperature Oligomeric Discotic Nematic Liquid Crystals over a Wide
      Temperature Range: Structure-Property Relationships.
AB  - The design and synthesis of three room-temperature discotic nematic (ND ) liquid
      crystals (LCs) is presented. The LC consists of an azobenzene core attached to
      which are four pentaalkynylbenzene (PA) units through flexible alkyl spacers. The
      presence of a short azo linking group provides more disorder in the system,
      thereby reducing the packing efficiency among the PA units and resulting into the
      formation of a room-temperature ND phase over a wide temperature range.
      Dielectric constant and birefringence studies were performed to gain further
      insights into the physical properties of the mesophase.

PMID- 28509392
TI  - Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular
      carcinoma in chronic hepatitis B virus carriers.
AB  - The relation between aflatoxin B1 (AFB1 ) and cirrhosis in chronic carriers of
      hepatitis B virus (HBV) remains inconclusive. This case-control study nested in a
      large community-based cohort aimed to assess the effect of AFB1 exposure on
      cirrhosis and HCC in chronic HBV carriers. Serum AFB1 -albumin adduct levels at
      study entry were measured in 232 cirrhosis cases, 262 HCC cases and 577 controls.
      Multivariate-adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs)
      were estimated using logistic regression. Among all chronic HBV carriers, the
      time intervals between study entry and diagnosis of HCC, cirrhosis, cirrhotic
      HCC, and non-cirrhotic HCC were all significantly (p < 0.0001) shorter in
      participants with high serum levels of AFB1 -albumin adducts than those with
      low/undetectable levels. There were significant dose-response relations with
      serum AFB1 -albumin adduct level at study entry for cirrhosis (p-trend = 0.0001)
      and cirrhotic HCC (p-trend < 0.0001) newly diagnosed within 9 years after entry
      as well as non-cirrhotic HCC (p-trend = 0.021) newly diagnosed within 4 years
      after entry. The aORs (95% CIs) for high versus undetectable serum AFB1 -albumin
      adduct levels were 2.45 (1.51-3.98) for cirrhosis (p = 0.0003), 5.47 (2.20-13.63)
      for cirrhotic HCC (p = 0.0003), and 5.39 (1.11-26.18) for non-cirrhotic (p =
      0.0368) HCC, respectively. There remained a significant dose-response relation
      between serum AFB1 -albumin adduct level and HCC risk (p-trend = 0.0291) in
      cirrhosis patients, showing an aOR (95% CI) of 3.04 (1.11-8.30) for high versus
      undetectable serum levels (p = 0.0299). It is concluded that AFB1 exposure may
      increase the risk of cirrhosis and HCC in a dose-response manner among chronic
      HBV carriers.

PMID- 28509395
TI  - DA-EPOCH-R for post-transplant lymphoproliferative disorders.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are a
      potentially fatal group of neoplasms arising in an immunodeficient environment.
      Although the cornerstone of treatment is reduced immunosuppression (RI), advanced
      cases often warrant treatment with chemoimmunotherapy. The chemoimmunotherapy
      regimen of dose-adjusted (DA)-EPOCH-R is superior to R-CHOP in HIV associated
      aggressive lymphomas, suggesting that it might also be favorable in the setting
      of PTLD. METHODS: We performed a retrospective analysis of patients with advanced
      monomorphic PTLD treated with first line DA-EPOCH-R in addition to RI at our
      institution from 2003-2016. RESULTS: Seven patients were included. Mean age was
      51 and mean time from transplant to diagnosis was 71 months. Six of the seven
      patients received a kidney transplant, six had stage III or IV disease, six had
      tumors that were EBV positive, and six completed therapy. All six patients who
      completed therapy achieved a complete response. Mean PFS and OS were 46.6 and
      52.6 months, respectively. Treatment was well-tolerated with no significant
      treatment related morbidity or mortality. CONCLUSIONS: Our findings support
      several observations in the literature that DA-EPOCH-R is efficacious and well
      tolerated for the treatment of advanced, monomorphic PTLD.

PMID- 28509396
TI  - Anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin in
      ovalbumin-sensitized rat.
AB  - BACKGROUND: Anti-inflammatory and antioxidant properties of curcumin have been
      shown. In this study, anti-inflammatory, antioxidant, and immunomodulatory
      effects of curcumin in sensitized rat were evaluated. METHODS: Six groups of rats
      including control (C), ovalbumin-sensitized (as a rat model of asthma, S), S
      groups treated with curcumin (Cu 0.15, 0.30, and 0.60 mg/mL), and 1.25 MUg/mL
      dexamethasone (S + D) were studied. Curcumin and dexamethasone were given in
      animals' drinking water during sensitization period. Total and differential WBC
      count, PLA2, TP, IFN-gamma, IL-4, IgE, oxidant, and antioxidant biomarker levels
      in bronchoalveolar lavage fluid (BALF) were examined. RESULTS: Total WBC,
      neutrophil and eosinophil counts, levels of PLA2, TP, IgE, IL-4, NO2 , NO3 , and
      MDA in BALF were increased but lymphocyte percentage, SOD, CAT, thiol, and IFN
      gamma levels and IFN-gamma/IL-4 ratio decreased in S animals compared to controls
      (P < 0.001 for all cases). Treatment with all concentrations of curcumin
      significantly improved total WBC, PLA2, TP, IgE, IL-4, IFN-gamma, IFN-gamma/IL-4
      ratio, SOD, thiol, NO2 , and NO3 compared to S group (P < 0.01 to P < 0.001). Two
      higher concentrations of curcumin significantly decreased neutrophil and
      eosinophil counts and MDA level but increased IFN-gamma, CAT and lymphocyte
      values compared to S group (P < 0.001 for all cases). Dexamethasone treatment
      also significantly improved most of the measured parameters (P < 0.05 to P <
      0.001) but it did not change IL-4 and IFN-gamma levels and IFN-gamma/IL-4 ratio.
      CONCLUSION: Anti-inflammatory, antioxidant, and immunomodulatory effects of
      curcumin with more specific immunomodulatory effect on Th1/Th2 balance compared
      to dexamethasone in sensitized rats was shown. (c) 2017 BioFactors, 43(4):567
      576, 2017.

PMID- 28509397
TI  - Sex differences in metabolic risk indicator of dementia in an elderly urban
      Korean population: A community-based cross-sectional study.
AB  - AIM: The aim of the present study was to evaluate the age-specific prevalence of
      dementia, and develop a metabolic risk indicator for dementia according to sex.
      METHODS: This cross-sectional study was carried out from September 2007 through
      December 2012 with 19 935 elderly participants in metropolitan Seoul, Korea.
      Multiphase assessments were used to measure metabolic risk factors and confirm
      dementia according to sex. Specifically, multivariate logistic regression
      analyses were used to identify how elderly men and women differed in regard to
      metabolic risk indicators of dementia. RESULTS: The adjusted prevalence rates of
      dementia in elderly Seoul residents were estimated at 4.9%, 6.1% and 5.6% in men,
      women and the overall population, respectively. Stroke conferred an odds ratio of
      5.14 (95% CI 3.91-6.77) and 2.55 (95% CI 2.01-3.25) in men and women,
      respectively. Additionally, within the female population, diabetes mellitus
      conferred an odds ratio of 1.29 (95% CI 1.09-1.53), whereas alcohol consumption
      conferred an odds ratio of 0.77 (95% CI 0.61-0.97). CONCLUSIONS: Stroke played a
      primary role as a metabolic risk indicator of dementia in elderly men, while
      diabetes mellitus and alcohol abstinence were important metabolic risk factors in
      elderly women. Taken together, the data show that when designing preventative
      measures against dementia based on metabolic risk, sex needs to be taken into
      account. Geriatr Gerontol Int 2017; 17: 2136-2142.

PMID- 28509399
TI  - Association of renin angiotensin antagonists with adverse perioperative events in
      patients undergoing elective orthopaedic surgery: a case-control study.
AB  - BACKGROUND: Renin angiotensin antagonists (RAA) may block protective vasopressor
      responses during surgery. Evidence linking RAA with intraoperative hypotension
      and perioperative adverse events is conflicting. AIM: To compare the incidence of
      intraoperative hypotension and adverse events between patients receiving or not
      receiving RAA. METHODS: This is a retrospective case-control study of 258
      consecutive patients who underwent elective total knee or hip replacement between
      1 January 2013 and 31 August 2016 and who were chronically prescribed a single
      blood pressure-lowering agent up to the time of surgery. Primary outcome measures
      were differences between patients receiving RAA (cases; n = 129) and patients
      receiving non-RAA medications (controls; n = 129) in incidence of intraoperative
      hypotension (systolic blood pressure <90 mmHg), perioperative acute kidney injury
      (AKI, >30% increase in serum creatinine from baseline on Day 1 post-operatively)
      and new onset major adverse cardiac or cerebrovascular events (MACCE) or in
      hospital death over 72 h post-operatively. RESULTS: Patients receiving RAA had
      significantly higher preoperative systolic blood pressure, greater prevalence of
      hypertension and chronic kidney disease, lower prevalence of ischaemic heart
      disease and lower cardiac risk compared to controls. Age, gender, type of
      operation, operative fitness, mode and duration of anaesthesia and prevalence of
      other types of cardiovascular disease, dyslipidaemia and diabetes were similar
      between groups. Compared to controls, patients receiving RAA had higher incidence
      of intraoperative hypotension (76.0 vs 45.9%, P < 0.001), AKI (11.6 vs 1.6%, P =
      0.002) and MACCE (6.2 vs 0%, P = 0.007), with all adverse events associated with
      intraoperative hypotension. CONCLUSION: This study provides further observational
      evidence of RAA-induced harm in patients undergoing elective surgery, although
      determining benefits and harms of preoperative withdrawal of RRA requires
      prospective randomised trials.

PMID- 28509398
TI  - The multicomponent antirestriction system of phage P1 is linked to capsid
      morphogenesis.
AB  - Bacterial Type I restriction-modification (R-M) systems present a major barrier
      to foreign DNA entering the bacterial cell. The temperate phage P1 packages
      several proteins into the virion that protect the phage DNA from host
      restriction. Isogenic P1 deletion mutants were used to reconstitute the
      previously described restriction phenotypes associated with darA and darB. While
      P1DeltadarA and P1DeltadarB produced the expected phenotypes, deletions of
      adjacent genes hdf and ddrA also produced darA-like phenotypes and deletion of
      ulx produced a darB-like phenotype, implicating several new proteins of
      previously unknown function in the P1 dar antirestriction system. Interestingly,
      disruption of ddrB decreased P1's sensitivity to EcoB and EcoK restriction.
      Proteomic analysis of purified virions suggests that packaging of antirestriction
      components into P1 virions follows a distinct pathway that begins with the
      incorporation of DarA and Hdf and concludes with DarB and Ulx. Electron
      microscopy analysis showed that hdf and darA mutants also produce abnormally high
      proportions of virions with aberrant small heads, which suggests Hdf and DarA
      play a role in capsid morphogenesis. The P1 antirestriction system is more
      complex than previously realized and is comprised of multiple proteins including
      DdrA, DdrB, Hdf, and Ulx in addition to DarA and DarB.

PMID- 28509400
TI  - Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P-gp In
      Vitro.
AB  - Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii
      Hook. f. (TWHF), which is a traditional herbal medicine widely used for the
      treatment of rheumatoid arthritis and autoimmune disease in the clinic. However,
      its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently
      reported which limited its clinical application. The aim of this study was to
      investigate the mechanism of glycyrrhetinic acid (GA) effecting on the
      elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp
      and multidrug resistance-associated proteins (MRPs) in this process. An ultra
      performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC
      ESI-MS) analytical method was established to determine the intracellular
      concentration of TP. In order to study the role of efflux transporters of P-gp
      and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux
      transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results
      showed that GA could enhance the elimination of TP and reduce the TP accumulation
      in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration
      of TP; in addition, GA co-incubation with verapamil significantly increased the
      TP cellular concentration compared with the control group. In conclusion, GA
      could reduce the accumulation of TP in HK-2 cells, which was related to P-gp.
      This is probably one of the mechanisms that TP combined with GA to detoxify its
      toxicity. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28509401
TI  - Transitions between marine and freshwater environments provide new clues about
      the origins of multicellular plants and algae.
AB  - Marine-freshwater and freshwater-marine transitions have been key events in the
      evolution of life, and most major groups of organisms have independently
      undergone such events at least once in their history. Here, we first compile an
      inventory of bidirectional freshwater and marine transitions in multicellular
      photosynthetic eukaryotes. While green and red algae have mastered multiple
      transitions in both directions, brown algae have colonized freshwater on a
      maximum of six known occasions, and angiosperms have made the transition to
      marine environments only two or three times. Next, we review the early
      evolutionary events leading to the colonization of current habitats. It is
      commonly assumed that the conquest of land proceeded in a sequence from marine to
      freshwater habitats. However, recent evidence suggests that early photosynthetic
      eukaryotes may have arisen in subaerial or freshwater environments and only later
      colonized marine environments as hypersaline oceans were diluted to the
      contemporary level. Although this hypothesis remains speculative, it is important
      to keep these alternative scenarios in mind when interpreting the current habitat
      distribution of plants and algae. Finally, we discuss the roles of structural and
      functional adaptations of the cell wall, reactive oxygen species scavengers,
      osmoregulation, and reproduction. These are central for acclimatization to
      freshwater or to marine environments. We observe that successful transitions
      appear to have occurred more frequently in morphologically simple forms and
      conclude that, in addition to physiological studies of euryhaline species,
      comparative studies of closely related species fully adapted to one or the other
      environment are necessary to better understand the adaptive processes.

PMID- 28509402
TI  - A combined hands-on teaching programme and clinical pathway focused on pleural
      ultrasound and procedure supervision transforms pleural procedure outcomes.
AB  - BACKGROUND: Management of pleural effusions is a common diagnostic and management
      problem. AIMS: We reviewed the outcomes from pleural procedures after the
      instigation of pleural effusion management guidelines, focusing on pleural
      ultrasound and a hands-on teaching programme followed by procedure supervision
      that enabled many operators to perform such procedures. METHODS: This is a
      retrospective analysis of all procedures performed for pleural effusions on
      medical patients. Outcomes were assessed prior to the instigation of pleural
      effusion management guidelines (pleural pathway) and hands-on teaching (January
      2010 to June 2011) and following these interventions (January 2012 to June 2013).
      RESULTS: A total of 171 procedures involving 129 patients (pre-pathway group) and
      146 procedures involving 115 patients (post-pathway group) was analysed. The rate
      of complications prior to the pleural pathway was 22.2% (38 of 171 procedures).
      Following the pathway, the rate of complications declined to 7.5% (11 of 146
      procedures, P < 0.003). The use of pleural ultrasound increased dramatically
      (72.5 vs 90.2%). The number of patients who underwent repeated procedures
      (defined as >=3) reduced dramatically (21 vs 7, P < 0.01). This improvement
      occurred using many supervised operators who completed the hands-on teaching
      programme (n = 32) and followed the pleural pathway (127 of 146 procedures).
      CONCLUSION: The instigation of a clinical pathway focused on the use of bedside
      pleural ultrasound, and teaching of drainage techniques with procedure
      supervision vastly improved patient outcomes. This not only allowed better
      quality of care for patients, it also provided the acquisition of new skills to
      medical staff, not limiting these skills to specialised staff.

PMID- 28509403
TI  - The zebrafish embryo as a model to quantify early inflammatory cell responses to
      biomaterials.
AB  - To rapidly assess early inflammatory cell responses provoked by biomaterials in
      the full complexity of the living organism, we developed a zebrafish embryo model
      which allows real time analysis of these responses to biomaterial microspheres.
      Fluorescently labeled microspheres with different properties were injected into
      embryos of selected transgenic zebrafish lines expressing distinct fluorescent
      proteins in their neutrophils and macrophages. Recruitment of leukocytes and
      their interactions with microspheres were monitored using fluorescence
      microscopy. We developed a novel method using ImageJ and the plugin ObjectJ
      project file "Zebrafish-Immunotest" for rapid and semi-automated fluorescence
      quantification of the cellular responses. In the embryo model we observed an
      ordered inflammatory cell response to polystyrene and poly (epsilon-caprolactone)
      microspheres, similar to that described for mammalian animal models. The
      responses were characterized by an early infiltration of neutrophils followed by
      macrophages, and subsequent differentially timed migration of these cells away
      from the microspheres. The size of microspheres (10 and 15 um) did not influence
      the cellular responses. Poly (epsilon-caprolactone) microspheres provoked a
      stronger infiltration of neutrophils and macrophages than polystyrene
      microspheres did. Our study shows the potential usefulness of zebrafish embryos
      for in vivo evaluation of biomaterial-associated inflammatory cell responses. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2522-2532, 2017.

PMID- 28509404
TI  - Family therapy for autism spectrum disorders.
AB  - BACKGROUND: Autism spectrum disorders (ASDs) are characterised by impairments in
      communication and reciprocal social interaction. These impairments can impact on
      relationships with family members, augment stress and frustration, and contribute
      to behaviours that can be described as challenging. Family members of individuals
      with ASD can experience high rates of carer stress and burden, and poor parental
      efficacy. While there is evidence to suggest that individuals with ASD and family
      members derive benefit from psychological interventions designed to reduce stress
      and mental health morbidity, and enhance coping, most studies to date have
      targeted the needs of either individuals with ASD, or family members. We wanted
      to examine whether family (systemic) therapy, aimed at enhancing communication,
      relationships or coping, is effective for individuals with ASD and their wider
      family network. OBJECTIVES: To evaluate the clinical effectiveness and
      acceptability of family therapy as a treatment to enhance communication or coping
      for individuals with ASD and their family members. If possible, we will also seek
      to establish the economic costs associated with family therapy for this clinical
      population. SEARCH METHODS: On 16 January 2017 we searched CENTRAL, MEDLINE,
      Embase, 10 other databases and three trials registers. We also handsearched
      reference lists of existing systematic reviews and contacted study authors in the
      field. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs
      investigating the effectiveness of family therapy for young people or adults with
      ASD or family members, or both, delivered via any modality and for an unspecified
      duration, compared with either standard care, a wait-list control, or an active
      intervention such as an alternative type of psychological therapy. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened each title and
      abstract and all full-text reports retrieved. To enhance rigour, 25% of these
      were independently screened by a third author. MAIN RESULTS: The search yielded
      4809 records. Of these, we retrieved 37 full-text reports for further scrutiny,
      which we subsequently excluded as they did not meet the review inclusion
      criteria, and identified one study awaiting classification. AUTHORS' CONCLUSIONS:
      Few studies have examined the effectiveness of family therapy for ASD, and none
      of these are RCTs. Further research studies employing methodologically robust
      trial designs are needed to establish whether family therapy interventions are
      clinically beneficial for enhancing communication, strengthening relationships,
      augmenting coping and reducing mental health morbidity for individuals with ASD
      and family members.

PMID- 28509405
TI  - Opportunities for expanding clinical trial enrollment for relapsed and refractory
      pediatric acute myeloid leukemia in the United States and Canada.

PMID- 28509406
TI  - High heparin content surface-modified polyurethane discs promote rapid and stable
      angiogenesis in full thickness skin defects through VEGF immobilization.
AB  - Three-dimensional scaffolds have the capacity to serve as an architectural
      framework to guide and promote tissue regeneration. Parameters such as the type
      of material, growth factors, and pore dimensions are therefore critical in the
      scaffold's success. In this study, heparin has been covalently bound to the
      surface of macroporous polyurethane (PU) discs via two different loading methods
      to determine if the amount of heparin content had an influence on the therapeutic
      affinity loading and release of (VEGF165 ) in full thickness skin defects. PU
      discs (5.4 mm diameter, 300 um thickness, and interconnected pore size of 150 um)
      were produced with either a low (2.5 mg/g) or high (6.6 mg/g) heparin content (LC
      and HC respectively), and were implanted into the modified dorsal skin chamber
      (MDSC) of C57BL/6 J mice with and without VEGF. Both low- and high-content discs
      with immobilized VEGF165 (LCV and HCV, respectively) presented accelerated
      neovascularization and tissue repair in comparison to heparin discs alone.
      However, the highest angiogenetic peak was on day 7 with subsequent stabilization
      for HCV, whereas other groups displayed a delayed peak on day 14. We therefore
      attribute the superior performance of HCV due to its ability to hold more
      VEGF165, based on its increased heparin surface coverage, as also demonstrated in
      VEGF elution dynamics. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 105A: 2543-2550, 2017.

PMID- 28509407
TI  - IL-1beta inhibits osteogenesis of human bone marrow-derived mesenchymal stem
      cells by activating FoxD3/microRNA-496 to repress wnt signaling.
AB  - IL-1beta, a major cytokine of proinflammatory response, has been implicated in
      bone loss. However, its effects on mesenchymal progenitor cells-associated bone
      regeneration remain elusive. Here, we investigated the role of microRNA for the
      regulation of osteogenesis by IL-1beta in human bone marrow-derived mesenchymal
      stem cells (hBMMSC). Our data suggested Homo sapiens (hsa)-miR-496 is induced by
      IL-1beta in hBMMSC and mediates the decreased beta-catenin expression. Reporter
      assays using the 3'-UTR of beta-catenin demonstrated sequence-dependent gene
      suppression with hsa-miR-496. IL-1beta activated hsa-miR-496 expression through a
      transcription factor, Foxhead box D3 protein (FoxD3). The activation of hsa-miR
      496 promoter in hBMMSC depended on a consensus FoxD3 binding motif. Under
      osteogenic differentiation, IL-1beta treatment or overexpressing hsa-miR-496
      attenuated bone mineralization and bone marker gene expressions in hBMMSC.
      Further, anti-miR-496 rescued the inhibitory effects of IL-1beta. Our findings
      suggest a pivotal role of hsa-miR-496 in linking inflammation to impaired bone
      regeneration, and provide a rationale for using appropriate hsa-miR-496
      inhibitors in the treatment of inflammation-associated bone loss.

PMID- 28509409
TI  - Soft tissue reconstruction and salvage of infected fixation hardware in lower
      extremity trauma.
AB  - BACKGROUND: Tibial fracture management may be complicated by infection of
      internal fixation hardware (iIFH) resulting in increased morbidity and amputation
      rate. When iIFH removal is not possible, salvage of the lower extremity is
      attempted through debridement, antibiotics, and vascularized soft tissue
      coverage. This study investigates lower extremity salvage with retention of iIFH.
      METHODS: Demographics, outcomes, and bacterial speciation in patients with tibial
      fractures at a level 1 trauma center from 2007 to 2014 were reviewed. The primary
      outcome was infection suppression, while secondary outcomes included limb
      salvage, amputation, and osseous union. RESULTS: Twenty-five patients underwent
      soft tissue reconstruction for salvage of iIFH. Average age was 41, 19 (76%) were
      male, average BMI 30.1 kg/m2 , 10 (40%) patients smoked. Tibial fractures were
      closed in 8 (32%), Gustilo-Anderson grade I in 1 (4%), II in 8 (32%), IIIb in 5
      (20%), and IIIc in 1 (4%). Staphylococcus was most commonly cultured with 11
      (44%) demonstrating methicillin-resistance. Soft tissue reconstruction was
      performed by local flap in 15 (60%) and free flap in 10 (40%). At an average of
      16.1 months, 19 (76%) hardware salvage patients demonstrated clinical suppression
      of infection, 11 of 19 (57.9%) patients had bony union, and 24 (96%) maintained a
      salvaged limb. One patient was amputated for recurrent infection. CONCLUSIONS:
      Following complex, infected tibial fractures, salvage of the lower extremity may
      be attempted even when iIFH cannot be removed. Thorough debridement, antibiotics,
      and vascularized soft tissue may suppress infection long enough to facilitate
      osseous union and subsequent removal of iIFH.

PMID- 28509408
TI  - Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What
      can be done?
AB  - Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when
      glycaemic targets are not met with diet and other hypoglycaemic agents. The
      initiation of IT improves glycaemic control and reduces the risk of microvascular
      complications. There is, however, an associated weight gain following IT, which
      may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to
      9 kg insulin-associated weight gain (IAWG) is reported to occur in the first year
      of initiating IT, predominantly caused by adipose tissue. The potential causes
      for this weight gain include an increase in energy intake linked to a fear of
      hypoglycaemia, a reduction in glycosuria, catch-up weight, and central effects on
      weight and appetite regulation. Patients with type 2 diabetes who are receiving
      IT often have multiple co-morbidities, including obesity, that are exacerbated by
      weight gain, making the management of their diabetes and obesity challenging.
      There are several treatment strategies for patients with type 2 diabetes, who
      require IT, that attenuate weight gain, help improve glycaemic control, and help
      promote body weight homeostasis. This review addresses the effects of insulin
      initiation and intensification on IAWG, and explores its potential underlying
      mechanisms, the predictors for this weight gain, and the available treatment
      options for managing and limiting weight gain.

PMID- 28509410
TI  - Anti-inflammatory, anti-osteoclastic, and antioxidant activities of genistein
      protect against alveolar bone loss and periodontal tissue degradation in a mouse
      model of periodontitis.
AB  - Genistein, a dietary polyphenol primarily found in soy products, has beneficial
      effects on bone. However, the effect of genistein on inflammatory periodontal
      destruction has not been investigated in detail. We explored whether genistein
      protects against lipopolysaccharide (LPS)/ligature-induced periodontitis in mice.
      We also examined the effect of genistein on LPS-stimulated inflammatory and
      oxidative stress using RAW 264.7 macrophages and human gingival fibroblasts
      (hGFs). The results from MUCT and histological analyses revealed that
      intraperitoneal injection of genistein (20 mg/kg body weight) daily for three
      weeks inhibited LPS-mediated alveolar bone loss and periodontal tissue
      degradation. The administration of genistein also inhibited osteoclast formation
      and the expression of inflammation-related molecules in the inflamed region of
      mice with periodontitis. Treatment with 30-70 MUM genistein significantly
      prevented osteoclast differentiation in receptor activator of nuclear factor
      kappaB ligand- or LPS-stimulated macrophages by suppressing the expression of
      osteoclast-specific molecules. The addition of genistein led to a dose-dependent
      inhibition of the expression of inflammation-related molecules both in LPS
      stimulated macrophages and hGFs. In addition, genistein at 50 MUM protected hGFs
      from LPS-mediated stresses such as mitochondrial impairment and cellular ROS
      accumulation. However, such protection was significantly diminished by combined
      treatment with 25 nM bafilomycin A1, a chemical autophagy inhibitor.
      Collectively, our results indicate that genistein protects against inflammatory
      periodontal damage by regulating autophagy induction and inhibiting osteoclast
      activation, the production of inflammation mediators, and mitochondrial oxidative
      damage. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2510
      2521, 2017.

PMID- 28509411
TI  - Variations in Duchenne muscular dystrophy course in a multi-ethnic UK population:
      potential influence of socio-economic factors.
AB  - AIM: To explore variation in clinical course and steroid treatment in Duchenne
      muscular dystrophy (DMD) by ethnic origin and socio-economic status. METHOD: In
      this longitudinal cohort study, clinical outcome was defined as age at loss of
      ambulation (LOA). Ages are presented as months for accurate calculation. Steroid
      use was reviewed against national guidelines. Kaplan-Meier survival analysis was
      used to determine probabilities over time of LOA. Log-rank test was used to
      evaluate comparisons between ethnic and socio-economic groups. RESULTS: From 2005
      to 2014, 71 children were newly diagnosed with DMD. Complete data were available
      on 69, including 33 of white British heritage and 23 of South Asian heritage.
      Mean age at diagnosis (without known family history) was 45.7 months; white
      British ethnicity 42.1 months (range 14-86mo), South Asian ethnicity 50.2 months
      (range 5-98mo). Twenty-four males lost ambulation. Those of South Asian heritage
      lost ambulation earlier (mean LOA 105.8mo [8y 10mo]) than those of white British
      heritage (mean LOA 117.8mo [9y 10mo]): log-rank test score 0.012 (p<0.05). Those
      most deprived did worse: mean age at LOA 130.0 months (10y 10mo) for the top 20
      per cent and 102.5 months (8y 6mo) in the lower 20 per cent: log-rank test score
      0.035 (p<0.05). The most socially deprived were diagnosed earlier and started
      steroids earlier. Of those of South Asian heritage, 18 per cent declined
      steroids, compared with 9 per cent of white British heritage. Also, 44 per cent
      of those of South Asian heritage stopped steroids compared with 17 per cent of
      those of white British heritage. INTERPRETATION: Patients from South Asian and
      deprived backgrounds had earlier LOA. Genetic disease modifiers are likely to be
      implicated, but social and cultural factors influence access to treatment.

PMID- 28509412
TI  - "Three Hits" Hypothesis for Developmental Origins of Health and Diseases in View
      of Cardiovascular Abnormalities.
AB  - "Fetal Origins of Adult Diseases" (FOAD) or "Barker hypothesis," also known as
      the developmental origins of health and diseases (DoHaD), was initially proposed
      by David Barker in the 1980s. Progress in past 2 to 3 decades demonstrated that
      many adult disorders, including hypertension, diabetes, obesity, cancer, and
      others, could be linked to poor development resulting from in utero insults.
      Utero-environments play a critical role in fetal development. Because the
      placenta and umbilical cord are the only important connections between the fetus
      and mother in the uterus, this review pays special attention to recent research
      and progress in the study of the relationship between those tissues and FOAD. We
      discuss the conception and possible underlying mechanisms of FOAD, and focus on
      cardiovascular diseases and epigenetic mechanisms. This review also summarizes
      physiology, pathology, and the important roles of fetoplacental vasculature,
      which might contribute to FOAD as initiators. We proposed the "Three hits"
      hypothesis that highlights the importance of intrauterine and early postnatal
      factors as contributors to FOAD, which could be significant for early prevention
      and treatments of FOAD. Birth Defects Research 109:744-757, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28509413
TI  - Microcarriers with Synthetic Hydrogel Surfaces for Stem Cell Expansion.
AB  - Microcarriers are scalable support surfaces for cell growth that enable high
      levels of expansion, and are particularly relevant for expansion of human
      mesenchymal stem cells (hMSCs). The goal of this study is to develop a
      poly(ethylene glycol) (PEG)-based microcarrier coating for hMSC expansion.
      Commercially available microcarriers do not offer customizability of microcarrier
      surface properties, including elastic modulus and surface cell adhesion ligands.
      The lab has previously demonstrated that tuning these material properties on PEG
      based hydrogels can modulate important cellular growth characteristics, such as
      cell attachment and expansion, which are important in microcarrier-based culture.
      Eosin-Y is adsorbed to polystyrene microcarriers and used as a photoinitiator for
      thiol-ene polymerization under visible light. Resultant PEG coatings are over 100
      um thick and localized to microcarrier surfaces. This thickness is relevant for
      cells to react to mechanical properties of the hydrogel coating, and coated
      microcarriers support hMSC attachment and expansion. hMSC expansion is highly
      favorable on coated microcarriers in serum-free media, with doubling times under
      25 h in the growth phase, and retained osteogenic and adipogenic differentiation
      capacity after culture on microcarriers. These microcarriers with defined,
      synthetic coatings enable tailorable surfaces for cell expansion that may be
      suitable for a variety of biomanufacturing applications.

PMID- 28509414
TI  - The Normal Fetal Pancreas.
AB  - OBJECTIVES: The aim of the study was to assess the sonographic feasibility of
      measuring the fetal pancreas and its normal development throughout pregnancy.
      METHODS: We conducted a cross-sectional prospective study between 19 and 36
      weeks' gestation. The study included singleton pregnancies with normal pregnancy
      follow-up. The pancreas circumference was measured. The first 90 cases were
      tested to assess feasibility. RESULTS: Two hundred ninety-seven fetuses of
      nondiabetic mothers were recruited during a 3-year period. The overall
      satisfactory visualization rate was 61.6%. The intraobserver and interobserver
      variability had high interclass correlation coefficients of of 0.964 and 0.967,
      respectively. A cubic polynomial regression described best the correlation of
      pancreas circumference with gestational age (r = 0.744; P < .001) and significant
      correlations also with abdominal circumference and estimated fetal weight
      (Pearson r = 0.829 and 0.812, respectively; P < .001). Modeled pancreas
      circumference percentiles for each week of gestation were calculated. During the
      study period, we detected 2 cases with overgrowth syndrome and 1 case with an
      annular pancreas. CONCLUSIONS: In this study, we assessed the feasibility of
      sonography for measuring the fetal pancreas and established a normal reference
      range for the fetal pancreas circumference throughout pregnancy. This database
      can be helpful when investigating fetomaternal disorders that can involve its
      normal development.

PMID- 28509416
TI  - The importance of CD39, CD43, CD81, and CD95 expression for differentiating B
      cell lymphoma by flow cytometry.
AB  - BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a
      combination of morphology, immunophenotype, recurrent cytogenetic aberration and
      clinical features. However, even with these diagnostic tools, a definitive
      diagnosis can be difficult to achieve. Therefore, the aim of this study was to
      assess the profile of CD39, CD43, CD81, and CD95 expressions in diffuse large B
      cell lymphoma (DLBCL), follicular lymphoma (FL), and Burkitt lymphoma (BL) cases.
      METHODS: To address this issue, we investigated the expression of CD39, CD43,
      CD81, and CD95 by eight-color flow cytometry in retrospective cases from 2014 to
      2016. RESULTS: The study included 27 adult patients diagnosed with DLBCL, FL, and
      BL during the study period. Four patients were diagnosed with germinal center B
      cell-like DLBCL (GCB DLBCL), seven with non-GCB DLBCL, nine with FL, and seven
      with BL. CD39 seems to be especially relevant to differentiate non-GCB DLBCL from
      BL and from FL. BL showed stronger expression of CD43 when compared to FL and GCB
      DLBCL. Moreover, CD43 may help to distinguish non-GCB DLBCL from GCB DLBCL. CD81
      expression was much stronger in BL when compared to the other three groups of
      patients. Lastly, CD95 may also help to distinguish BL from the other subtypes,
      as BL cells expressed this antigen at low levels. CONCLUSIONS: In combination,
      CD39, CD43, CD81, and CD95 expressions appear to be helpful to distinguish CD10+
      BCL, particularly BL. Phenotypic distinction between FL and GCB DLBCL remains
      challenging and requires further studies. (c) 2017 International Clinical
      Cytometry Society.

PMID- 28509415
TI  - Ratings of affective and interpersonal tendencies differ for grandiose and
      vulnerable narcissism: A replication and extension of Gore and Widiger (2016).
AB  - OBJECTIVE: Theoretical conceptions of narcissism have long been characterized by
      two seemingly opposing poles: grandiosity and vulnerability. The goal of the
      current study was to investigate the extent to which traits associated with one
      profile are perceived to co-occur with the other within an individual. METHOD:
      Lay raters (N = 862; 56% female; 80% Caucasian; Mage  = 37) recruited from
      Amazon's MTurk were assigned to one of four conditions in which they rated how
      often a series of narcissistic traits were displayed by a prototypical grandiose
      narcissist, a vulnerable narcissist, a close friend, or themselves. Vulnerable
      narcissism items were specifically worded to assess internalizing- versus
      externalizing-based emotional responses. RESULTS: Results suggest that
      grandiosely narcissistic individuals are seen as responding angrily to ego
      threatening situations, whereas vulnerably narcissistic individuals are seen as
      responding with a broader array of negative emotions, including anger, sadness,
      and shame. In contrast, vulnerably narcissistic individuals were not rated as
      consistently demonstrating behaviors, attitudes, or cognitions associated with
      grandiose narcissism. CONCLUSIONS: Grandiose and vulnerable narcissistic
      individuals both exhibit anger in response to ego threat, but sadness/shame
      responses are more characteristic of vulnerable narcissism.

PMID- 28509417
TI  - Overexpression of ubiquitin specific peptidase 14 predicts unfavorable prognosis
      in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Ubiquitin specific peptidase 14 (USP14), a deubiquitinating enzyme,
      has been documented as a key element to regulate the proteolysis function of
      proteasomes and an attractive therapeutic target for several cancers. Herein, we
      elucidate the role of USP14 in predicting the prognosis of patients with
      esophageal squamous cell carcinoma (ESCC). METHODS: USP14 expression was detected
      in ESCC tissues and matched adjacent non-tumorous tissues by quantitative real
      time reverse transcription-PCR and immunohistochemistry. Kaplan-Meier survival
      analysis was used to assess the correlation between USP14 expression and
      prognosis in ESCC patients. Univariate and multivariate analysis was conducted
      with a Cox proportional hazards model to determine whether USP14 is an
      independent prognostic factor. RESULT: Overexpression of USP14 was observed in
      approximately 60% of tested ESCC samples compared to their paired non-tumor
      esophageal tissues at both RNA and protein levels, and was significantly
      associated with distant metastasis (P = 0.001). Kaplan-Meier analysis showed that
      USP14 overexpression was related to poorer overall patient survival. Univariate
      and multivariate analyses demonstrated that USP14 was an independent risk factor
      for overall survival. CONCLUSION: The findings in this study suggest that USP14
      could be used as a potential prognostic marker for ESCC patients.

PMID- 28509418
TI  - Sirenomelia: A Multi-systemic Polytopic Field Defect with Ongoing Controversies.
AB  - The most impressive phenotypic appearance of sirenomelia is the presence of a 180
      degrees -rotated, axially positioned, single lower limb. Associated
      gastrointestinal and genitourinary anomalies are almost always present. This rare
      anomaly is still the subject of ongoing controversies concerning its nosology,
      pathogenesis, and possible genetic etiology. Sirenomelia can be part of a
      syndromic continuum, overlapping with other complex conditions including caudal
      dysgenesis and VATER/VACTERL/VACTERL-H associations, which could all be part of a
      heterogeneous spectrum, and originate from an early defect in blastogenesis. It
      is imaginable that different "primary field defects," whether or not genetically
      based, induce a spectrum of caudal malformations. In the current study, we review
      the contemporary hypotheses and conceptual approaches regarding the etiology and
      pathogenesis of sirenomelia, especially in the context of concomitant conditions.
      To expand on the latter, we included the external and internal dysmorphology of
      one third trimester sirenomelic fetus from our anatomical museum collection, in
      which multiple concomitant but discordant anomalies were observed compared with
      classic sirenomelia, and was diagnosed as VACTERL-H association with sirenomelia.
      Birth Defects Research 109:791-804, 2017. (c) 2017 The Authors. Birth Defects
      Research Published by Wiley Periodicals, Inc.

PMID- 28509420
TI  - The magnitude of Indigenous and non-Indigenous oral health inequalities in
      Brazil, New Zealand and Australia.
AB  - OBJECTIVE: To compare the magnitude of relative oral health inequalities between
      Indigenous and non-Indigenous persons from Brazil, New Zealand and Australia.
      METHODS: Data were from surveys in Brazil (2010), New Zealand (2009) and
      Australia (2004-06 and 2012). Participants were aged 35-44 years and 65-74 years.
      Indigenous and non-Indigenous inequalities were estimated by prevalence ratios
      (PR) and their corresponding 95% confidence intervals (CI), adjusting for sex,
      age and income. Outcomes included inadequate dentition, untreated dental caries,
      periodontal disease and the prevalence of "fair" or "poor" self-rated oral health
      in Australia and New Zealand, and satisfaction with mouth/teeth in Brazil (SROH).
      RESULTS: Irrespective of country, Indigenous persons had worse oral health than
      their non-Indigenous counterparts in all indicators. The magnitude of these
      ratios was greatest among Indigenous and non-Indigenous Australians, who, after
      adjustments, had 2.77 times the prevalence of untreated dental caries (95% CI
      1.76, 4.37), 5.14 times the prevalence of fair/poor SROH (95% CI 2.53, 10.43).
      CONCLUSION: Indigenous people had poorer oral health than their non-Indigenous
      counterparts, regardless of setting. The magnitude of the relative inequalities
      was greatest among Indigenous Australians for untreated dental decay and poor
      SROH.

PMID- 28509419
TI  - Live-cell CRISPR imaging in plants reveals dynamic telomere movements.
AB  - Elucidating the spatiotemporal organization of the genome inside the nucleus is
      imperative to our understanding of the regulation of genes and non-coding
      sequences during development and environmental changes. Emerging techniques of
      chromatin imaging promise to bridge the long-standing gap between sequencing
      studies, which reveal genomic information, and imaging studies that provide
      spatial and temporal information of defined genomic regions. Here, we demonstrate
      such an imaging technique based on two orthologues of the bacterial clustered
      regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated
      protein 9 (Cas9). By fusing eGFP/mRuby2 to catalytically inactive versions of
      Streptococcus pyogenes and Staphylococcus aureus Cas9, we show robust
      visualization of telomere repeats in live leaf cells of Nicotiana benthamiana. By
      tracking the dynamics of telomeres visualized by CRISPR-dCas9, we reveal dynamic
      telomere movements of up to 2 MUm over 30 min during interphase. Furthermore, we
      show that CRISPR-dCas9 can be combined with fluorescence-labelled proteins to
      visualize DNA-protein interactions in vivo. By simultaneously using two dCas9
      orthologues, we pave the way for the imaging of multiple genomic loci in live
      plants cells. CRISPR imaging bears the potential to significantly improve our
      understanding of the dynamics of chromosomes in live plant cells.

PMID- 28509421
TI  - CRISPR/Cas9-mediated targeted mutagenesis of GmFT2a delays flowering time in soya
      bean.
AB  - Flowering is an indication of the transition from vegetative growth to
      reproductive growth and has considerable effects on the life cycle of soya bean
      (Glycine max). In this study, we employed the CRISPR/Cas9 system to specifically
      induce targeted mutagenesis of GmFT2a, an integrator in the photoperiod flowering
      pathway in soya bean. The soya bean cultivar Jack was transformed with three
      sgRNA/Cas9 vectors targeting different sites of endogenous GmFT2a via
      Agrobacterium tumefaciens-mediated transformation. Site-directed mutations were
      observed at all targeted sites by DNA sequencing analysis. T1-generation soya
      bean plants homozygous for null alleles of GmFT2a frameshift mutated by a 1-bp
      insertion or short deletion exhibited late flowering under natural conditions
      (summer) in Beijing, China (N39 degrees 58', E116 degrees 20'). We also found
      that the targeted mutagenesis was stably heritable in the following T2
      generation, and the homozygous GmFT2a mutants exhibited late flowering under both
      long-day and short-day conditions. We identified some 'transgene-clean' soya bean
      plants that were homozygous for null alleles of endogenous GmFT2a and without any
      transgenic element from the T1 and T2 generations. These 'transgene-clean'
      mutants of GmFT2a may provide materials for more in-depth research of GmFT2a
      functions and the molecular mechanism of photoperiod responses in soya bean. They
      will also contribute to soya bean breeding and regional introduction.

PMID- 28509422
TI  - Evaluation of the Medicinal Potential of Two Ruthenium(II) Polypyridine Complexes
      as One- and Two-Photon Photodynamic Therapy Photosensitizers.
AB  - Two [Ru(phen)2 dppz]2+ derivatives (phen=1,10-phenantroline, dppz=dipyrido[3,2
      a:2',3'-c]phenazine) with different functional groups on the dppz ligand [dppz
      7,8-(OMe)2 (1), dppz-7,8-(OH)2 (2)] have been synthesized, characterized and
      investigated as photosensitizers (PSs) for photodynamic therapy (PDT) against
      cancer. Both complexes showed intense red phosphorescence and promising singlet
      oxygen (1 O2 ) quantum yields of 75 % (1) and 54 % (2) in acetonitrile. Complex 1
      (logPo/w =-0.52, 2.4 nmol Ru per mg protein) was found to be more lipophilic,
      having also a higher cellular uptake efficiency compared to 2 (logPo/w =-0.20,
      0.9 nmol Ru per mg protein). Complex 1 localized evenly in HeLa cells whereas 2,
      was mainly visualized in the cell membrane by confocal microscopy. In the dark,
      complex 1 (IC50 =36.5 MUm) was found to be more toxic than complex 2 (IC50 >100
      MUm) on a HeLa cells monolayer. Importantly, in view of PDT applications, both
      complexes were found to be non-toxic in the dark towards multicellular HeLa
      spheroids (IC50 >100 MUm). Upon one-photon irradiation (420 nm, 9.27 J cm-2 ), 1
      exhibited higher phototoxicity (IC50 =3.1 MUm) than 2 (IC50 =16.7 MUm) on HeLa
      cell monolayers. When two-photon irradiation (800 nm, 9.90 J cm-2 ) was applied,
      only 1 (IC50 =9.5 MUm) was found to be active toward HeLa spheroids. This study
      demonstrates that the functional group on the intercalative ligand has a strong
      influence on the cellular localization and anticancer activity of RuII
      polypyridyl complexes.

PMID- 28509423
TI  - Analysis of the relationship between the double transverse foramen and the
      possibility of developing clinical symptoms after whiplash.
AB  - Currently, there is no information about the possibility of developing clinical
      symptoms after whiplash in double transverse foramen subjects. Our aim was to
      test whether subjects with double transverse foramen have an increased risk of
      presenting with an acute headache, dizziness, vertebral artery dissection, and
      vomiting after whiplash.We recorded the absence/presence of double transverse
      foramen, and the absence/presence of neck pain, acute headache, dizziness,
      vertebral artery dissection, and vomiting in 85 patients who had suffered
      whiplash injuries in car rear-end impacts in road traffic accidents. We used the
      odds ratio test to determine whether double transverse foramen subjects are at a
      higher risk of developing an acute headache, dizziness, and vomiting than non
      double transverse foramen subjects.Although double transverse foramen subjects
      presented with more clinical symptoms after whiplash, the odds ratio test
      revealed that their risks of developing acute headache (P = 0.30), dizziness (P =
      0.09), or vomiting (P = 0.18) were not significantly greater than in the control
      group.Double transverse foramen subjects are not at a higher risk of presenting
      acute headache, dizziness, vertebral artery dissection, and vomiting after
      whiplash. Clin. Anat. 30:761-766, 2017. (c) 2017Wiley Periodicals, Inc.

PMID- 28509424
TI  - Inhibition of Prion Propagation by 3,4-Dimethoxycinnamic Acid.
AB  - Neurodegenerative diseases are associated with accumulation of amyloid-type
      protein misfolding products. Prion protein (PrP) is known for its ability to
      aggregate into soluble oligomers that in turn associate into amyloid fibrils.
      Preventing the formation of these infective and neurotoxic entities represents a
      viable strategy to control prion diseases. Numerous attempts to find dietary
      compounds with anti-prion properties have been made; however, the most promising
      agent found so far was curcumin, which is poorly soluble and merely bioavailable.
      In the present work, we identify 3,4-dimethoxycinnamic acid (DMCA) which is a
      bioavailable coffee component as a perspective anti-prion compound. 3,4
      Dimethoxycinnamic acid was found to bind potently to prion protein with a Kd of
      405 nM. An in vitro study of DMCA effect on PrP oligomerization and
      fibrillization was undertaken using isothermal titration calorimetry (ITC),
      dynamic light scattering (DLS) and circular dichroism (CD) methodologies. We
      demonstrated that DMCA affects PrP oligomer formation reducing the oligomer
      content by 30-40%, and enhancing SH-SY5Y cell viability treated with prion
      oligomers. Molecular docking studies allowed to suggest a site where DMCA is able
      to bind stabilizing PrP tertiary structure. We suggest that DMCA is a perspective
      dietary compound for prophylaxis of neurodegenerative diseases that needs further
      research. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28509425
TI  - Methods of fixation of intraocular lenses according to the anatomical structures
      in trauma eyes.
AB  - Ocular trauma can lead to severe visual impairment and morbidity, depending on
      the anatomical structures affected. The main causes of ocular trauma include
      foreign bodies, impact by an object, falls, and chemicals. Most ocular traumas
      occur in children or young male adults. A meticulous slit lamp examination is
      crucial for assessing all anatomical structures. Trauma to the crystalline lens
      can result in dislocation, an intralenticular foreign body, cataract,
      fragmentation, and capsular breach. An intraocular lens (IOL) can endure
      subluxation or luxation under the conjunctiva, into the anterior chamber or the
      vitreous, or can be extruded. The surgical approach depends on the condition and
      morphology of the lens and the anatomical structures surrounding it. If there is
      capsular bag support, a secondary IOL can be placed in the sulcus using remnants
      of the damaged capsule. If there is no capsular bag support, a secondary IOL can
      be fixated to the anterior chamber angle, to the iris, or to the sclera. A
      detailed history of injury cannot always be obtained in trauma settings. Proper
      education, supervision, and certified safety eye protectors could prevent up to
      90% of ocular injuries. Lens trauma can be treated with various surgical
      procedures and fixation techniques, which nevertheless require advanced surgical
      skills owing to the fine anatomical structure of the anterior segment. A careful
      surgical strategy should be established for a globe reconstruction after trauma
      with secondary lens implantation. Clin. Anat. 31:6-15, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28509427
TI  - Self-Supplying O2 through the Catalase-Like Activity of Gold Nanoclusters for
      Photodynamic Therapy against Hypoxic Cancer Cells.
AB  - Photodynamic therapy (PDT) typically involves oxygen (O2 ) consumption and
      therefore suffers from greatly limited anticancer therapeutic efficacy in tumor
      hypoxia. Here, it is reported for the first time that amine-terminated, PAMAM
      dendrimer-encapsulated gold nanoclusters (AuNCs-NH2 ) can produce O2 for PDT via
      their intrinsic catalase-like activity. The AuNCs-NH2 not only show optimum H2 O2
      consumption via the catalase-like activity over the physiological pH range (i.e.,
      pH 4.8-7.4), but also extend such activity to acidic conditions. The possible
      mechanism is deduced from that the enriched tertiary amines of dendrimers are
      easily protonated in acidic solutions to facilitate the preadsorption of OH on
      the metal surface, thereby favorably triggering the catalase-like reaction. By
      taking advantage of the exciting feature on AuNCs-NH2 , the possibility to supply
      O2 via the catalase-like activity of AuNCs-NH2 for PDT against hypoxia of cancer
      cells was further studied. This proof-of-concept study provides a simple way to
      combine current O2 -dependent cancer therapy of PDT to overcome cancer cell
      hypoxia, thus achieving more effective anticancer treatments.

PMID- 28509426
TI  - Precise Patterning of Organic Single Crystals via Capillary-Assisted Alternating
      Electric Field.
AB  - Owing to the extraordinary properties, organic micro/nanocrystals are important
      building blocks for future low-cost and high-performance organic electronic
      devices. However, integrated device application of the organic micro/nanocrystals
      is hampered by the difficulty in high-throughput, high-precision patterning of
      the micro/nanocrystals. In this study, the authors demonstrate, for the first
      time, a facile capillary-assisted alternating-electric field method for the large
      scale assembling and patterning of both 0D and 1D organic crystals. These
      crystals can be precisely patterned at the photolithography defined
      holes/channels at the substrate with the yield up to 95% in 1 mm2 . The mechanism
      of assembly kinetics is systematically studied by the electric field distribution
      simulation and experimental investigations. By using the strategy, various
      organic micro/nanocrystal patterns are obtained by simply altering the geometries
      of the photoresist patterns on substrates. Moreover, ultraviolet photodetectors
      based on the patterned Alq3 micro/nanocrystals exhibit visible-blind
      photoresponse with high sensitivity as well as excellent stability and
      reproducibility. This work paves the way toward high-integration, high
      performance organic electronic, and optoelectronic devices from the organic
      micro/nanocrystals.

PMID- 28509428
TI  - Including Langerhans cell histiocytosis in the differential diagnosis of skin
      tumors with osteoclast-like multinucleated giant cells.

PMID- 28509429
TI  - Chronic kidney disease: A likely underestimated component of multimorbidity in
      older patients with chronic obstructive pulmonary disease.
AB  - The coexistence of chronic kidney disease and chronic obstructive pulmonary
      disease, two age-related conditions, has important clinical and prognostic
      implications. Respiratory failure is associated with important changes in
      glomerular and tubulointerstitial function. In contrast, renal failure can affect
      lung function, mainly by adding a restrictive component or causing complications,
      such as uremic pulmonary edema and pleural effusion. The effect of age on renal
      and pulmonary function adds to the complexity of the interplay between the kidney
      and the lung in these patients. Chronic kidney disease also represents an
      important risk factor for adverse drug reactions in older chronic obstructive
      pulmonary disease patients in which multimorbidity and polypharmacy are highly
      prevalent. Finally, an additive effect of chronic kidney disease and chronic
      obstructive pulmonary disease might also contribute to the pathophysiology of
      sarcopenia. Nevertheless, several gaps in our knowledge of the lung-kidney
      interplay still exist, thus suggesting further basic and clinical research on
      this topic. Geriatr Gerontol Int 2017; 17: 1770-1788.

PMID- 28509430
TI  - Trapping CO2 by Adduct Formation with Nitrogen Heterocyclic Carbenes (NHCs): A
      Theoretical Study.
AB  - Carbon dioxide can form compounds with nitrogen heterocyclic carbenes (NHCs)
      based on azoles through noncovalent interactions or by covalent bonding. A narrow
      dependence on the carbene structure has been observed for the preference for one
      or the other type of bonding, as revealed by a series of physicochemical
      descriptors. In our survey, a set of NHCs based on the azole family (three
      classical, three abnormal, and one remote) was shown to bind CO2 at the accurate
      G4MP2 computational level. In most cases, exothermic reaction profiles towards
      the covalently bound form were found, which reached stabilization enthalpies of
      up to -77 kJ mol-1 for the remote carbene case. Both noncovalent and covalent
      minima and the corresponding transition state that connects them have been
      identified as stationary points along the reaction coordinate.

PMID- 28509431
TI  - Golga5 is dispensable for mouse embryonic development and postnatal survival.
AB  - Golgins are a family of coiled-coil proteins located at the cytoplasmic surface
      of the Golgi apparatus and have been implicated in maintaining Golgi structural
      integrity through acting as tethering factors for retrograde vesicle transport.
      Whereas knockdown of several individual golgins in cultured cells caused Golgi
      fragmentation and disruption of vesicle trafficking, analysis of mutant mouse
      models lacking individual golgins have discovered tissue-specific developmental
      functions. Recently, homozygous loss of function of GOLGA2, of which previous in
      vitro studies suggested an essential role in maintenance of Golgi structure and
      in mitosis, has been associated with a neuromuscular disorder in human patients,
      which highlights the need for understanding the developmental roles of the
      golgins in vivo. We report here generation of Golga5-deficient mice using
      CRISPR/Cas9-mediated genome editing. Although knockdown studies in cultured cells
      have implicated Golga5 in maintenance of Golgi organization, we show that Golga5
      is not required for mouse embryonic development, postnatal survival, or
      fertility. Moreover, whereas Golga5 is structurally closely related to Golgb1, we
      show that inactivation of Golga5 does not enhance the severity of developmental
      defects in Golgb1-deficient mice. The Golga5-deficient mice enable further
      investigation of the roles and functional specificity of golgins in development
      and diseases.

PMID- 28509432
TI  - Feasibility assessment of shear wave elastography to lumbar back muscles: A
      Radioanatomic Study.
AB  - Low back pain is often associated with tensional changes in the paraspinal
      muscles detected by palpatory procedures. Shear wave elastography (SWE), recently
      introduced, allows the stiffness of muscles to be assessed noninvasively. The aim
      of this work was to study the feasibility of using SWE on the three main lumbar
      back muscles (multifidus, longissimus, and iliocostalis) in vivo after analyzing
      their muscular architecture ex vivo. We determined the orientation of fibers in
      the multifidus, longissimus, and iliocotalis muscles in seven fresh cadavers
      using gross anatomy and B-Mode ultrasound imaging. We then quantified the
      stiffness of these three muscles at the L3 level ex vivo and in 16 healthy young
      adults. Little pennation was observed in the longissimus and iliocostalis, in
      which the direction of fibers was almost parallel to the line of spinous
      processes. The multifidus appeared as a multiceps and multipennate muscle. Given
      the random layering of millimetric fascicles, tendons, and fatty spaces, the
      multifidus had multiple fiber orientations. Muscular fascicles and fibers were
      oriented from 9 degrees  to 22 degrees  to the line of spinous processes. The
      shear moduli related to stiffness were 6.9 +/- 2.7 kPa for the longissimus, 4.9
      +/- 1.4 kPa for the iliocostalis, and 5.4 +/- 1.6 kPa for the multifidus. SWE is
      a feasible method for quantifying the stiffness of the lumbar back muscles. Clin.
      Anat. 30:774-780, 2017. (c) 2017Wiley Periodicals, Inc.

PMID- 28509433
TI  - Dosing anticancer drugs in infants: Current approach and recommendations from the
      Children's Oncology Group's Chemotherapy Standardization Task Force.
AB  - An analysis of dose modifications for infants in 29 Children's Oncology Group
      protocols across 10 cancer types revealed 11 sets of criteria defining the infant
      population using age, weight, body surface area (BSA), or a combination of these
      parameters and eight dose modification methods. A new method of dosing anticancer
      drugs in infants was developed based on the rationale that prior modifications
      were implemented to reduce toxicity, which is not cancer-specific. The new method
      uses BSA dose banding in dosing tables for infants and children with a BSA <0.6
      m2 and gradually transitions from body weight based to BSA-based dosing.

PMID- 28509434
TI  - New liver - Fresh microbiome: Implications on brain function.

PMID- 28509435
TI  - Inpatient iron deficiency detection and management: how do general physicians and
      gastroenterologists perform in a tertiary care hospital?
AB  - BACKGROUND: Iron deficiency (ID) is often an indicator of underlying pathology.
      Early detection and treatment avoids long-term morbidity and allows for prompt
      iron repletion, avoiding ID anaemia (IDA) and the need for blood transfusion.
      AIM: To evaluate the management of ID in two internal medicine units (general
      medical (GM) and gastroenterology (GE)) in a large metropolitan hospital and
      compare it to international guidelines. METHODS: All consecutive inpatient
      admissions in the GM and GE units were retrospectively reviewed until 40 patients
      in each service were identified with anaemia and/or microcytic hypochromic blood
      counts. Patient records and electronic discharge summaries were then reviewed to
      assess the recognition, investigation and management of these abnormalities.
      RESULTS: Overall, only 60% (48/80) of the cases of microcytic hypochromic picture
      and/or anaemia were recognised. Cases were more likely to be detected under the
      GE unit, 77.5% (31/40) versus 42% (17/40) in GM (P < 0.002). Of the 31 recognised
      GE cases, 28 (90%) were investigated further with iron studies and/or endoscopic
      procedures. ID was confirmed in nearly half (5/11) of those tested; however, only
      2 of 5 received iron replacement. Among GM patients, only 11 of the 17 recognised
      cases (64%) were investigated further. Iron studies were performed in all 11,
      confirming IDA in 4 (36%), all of whom received intravenous iron. A faecal human
      haemoglobin test was performed in two GM patients and one GE patient. CONCLUSION:
      There remains significant room for improvement in the recognition, investigation
      and management of ID in hospital practice in Australia.

PMID- 28509436
TI  - Pollinators shift to nectar robbers when florivory occurs, with effects on
      reproductive success in Iris bulleyana (Iridaceae).
AB  - Studies have indicated that florivory and nectar robbing may reduce reproductive
      success of host plants. However, whether and how these effects might interact
      when plants are simultaneously attacked by both florivores and nectar robbers
      still needs further investigation. We used Iris bulleyana to detect the
      interactions among florivory, nectar robbing and pollination, and moreover, their
      effects on plant reproductive success. Field investigations and hand-pollination
      treatments were conducted on two experimental plots from a natural population, in
      which Experimental plot was protected from florivores and Control plot was not
      manipulated. The flower calyx was bitten by sawflies to consume the nectary, and
      three bumblebee species were pollinators. In addition, the short-tongued
      pollinator, Bombus friseanus, was the only robber when there was a hole made by a
      sawfly. The bumblebee had significantly shortened flower handling time when
      robbing, as compared to legitimate visits. Pollinator visitation and seed
      production decreased significantly in damaged flowers. However, seed production
      per flower after supplementary hand-pollination did not differ significantly
      between damaged and undamaged flowers. Compared to the Experimental plot,
      bumblebees visited fewer flowers per plant in a foraging bout in the Control
      plot. The flowers damaged by florivory allowed B. friseanus to shift to a nectar
      robber. Florivory and nectar robbing collectively decreased plant reproductive
      success by consuming nectar resources, which may reduce attractiveness to
      pollinators of the damaged flowers. However, the changes in pollinator behaviour
      might be beneficial to the plant by reducing the risk of geitonogamous mating.

PMID- 28509437
TI  - Detection of Avian Influenza Virus from Cloacal Swabs Using a Disposable Well
      Gate FET Sensor.
AB  - Current methods to detect avian influenza viruses (AIV) are time consuming and lo
      inw sensitivity, necessitating a faster and more sensitive sensor for on-site
      epidemic detection in poultry farms and urban population centers. This study
      reports a field effect transistor (FET) based AIV sensor that detects
      nucleoproteins (NP) within 30 minutes, down to an LOD of 103 EID50 mL-1 from a
      live animal cloacal swab. Previously reported FET sensors for AIV detection have
      not targeted NPs, an internal protein shared across multiple strains, due to the
      difficulty of field-effect sensing in a highly ionic lysis buffer. The AIV sensor
      overcomes the sensitivity limit with an FET-based platform enhanced with a
      disposable well gate (DWG) that is readily replaceable after each measurement. In
      a single procedure, the virus-containing sample is immersed in a lysis buffer
      mixture to expose NPs to the DWG surface. In comparison with commercial AIV rapid
      kits, the AIV sensor is proved to be highly sensitive, fast, and compact, proving
      its potential effectiveness as a portable biosensor.

PMID- 28509439
TI  - Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural
      Product YM-254890, Targeting the Gq Protein.
AB  - Extracellular signals perceived by G protein-coupled receptors are transmitted
      via G proteins, and subsequent intracellular signaling cascades result in a
      plethora of physiological responses. The natural product cyclic depsipeptides YM
      254890 and FR900359 are the only known compounds that specifically inhibit
      signaling mediated by the Gq subfamily. In this study we exploit a newly
      developed synthetic strategy for this compound class in the design, synthesis,
      and pharmacological evaluation of eight new analogues of YM-254890. These
      structure-activity relationship studies led to the discovery of three new
      analogues, YM-13, YM-14, and YM-18, which displayed potent and selective Gq
      inhibitory activity. This provides pertinent information for the understanding of
      the Gq inhibitory mechanism by this class of compounds and importantly provides a
      pathway for the development of labeled YM-254890 analogues.

PMID- 28509438
TI  - Deguelin inhibits epithelial-to-mesenchymal transition and metastasis of human
      non-small cell lung cancer cells by regulating NIMA-related kinase 2.
AB  - BACKGROUND: Non-small cell lung cancer is a lethal malignancy with a high
      mortality rate. Deguelin displays an anti-tumor effect and inhibits metastasis in
      various cancers. The aberrant expression of NIMA-related kinase 2 (NEK2)
      indicates poor prognosis and induces epithelial-to-mesenchymal transition (EMT)
      and metastasis processes. However, the underlying mechanism between deguelin and
      NEK2 has remained elusive. METHODS: NSCLC cell lines were treated with deguelin.
      Wound-healing and invasion assays were applied to study the inhibitory effect of
      deguelin on NSCLC cells. EMT markers, E-cadherin and Vimentin, were also detected
      by Western blot. NEK2 protein and messenger RNA expression levels were evaluated
      when NSCLC cells were treated with different concentrations of deguelin. The
      effect of NEK2 on NSCLC cell metastasis was evaluated through NEK2 knockdown. To
      investigate whether deguelin induced EMT by regulating NEK2, we overexpressed
      NEK2 in both NCI-H520 and SK-MES-1 cell lines, and then used real time-PCR to
      study the E-cadherin and Vimentin messenger RNA expression in both NSCLC cells.
      RESULTS: Deguelin inhibited migration and invasion processes in NSCLC cell lines
      and decreased NEK2 expression in a concentration-dependent manner. Furthermore,
      NEK2 knockdown inhibited NSCLC cell migration and invasion. Finally,
      overexpressing NEK2 in NCI-H520 and SK-MES-1 cells could restore the inhibition
      of metastasis induced by deguelin. CONCLUSIONS: Deguelin could inhibit EMT and
      metastasis, while overexpression of NEK2 promotes these processes. Deguelin could
      decrease NEK2 expression, while NEK2 overexpression could restore deguelin
      induced inhibition of metastasis.

PMID- 28509440
TI  - No improvement in clinical trial enrollment for adolescents and young adults with
      cancer at a children's hospital.
AB  - BACKGROUND: We have previously published data from 2001 to 2006 showing that
      adolescent and young adult (AYA) oncology patients have significantly lower
      therapeutic clinical trial enrollment rates than younger patients. Our objective
      was to determine if the enrollment of AYA patients on therapeutic studies at the
      same institution has improved in recent years with the greater focus on this
      population locally and nationally. METHODS: We retrospectively analyzed cancer
      registry data at the Children's Hospital of Pittsburgh (CHP) for all new
      oncologic diagnoses between January 2010 and December 2014. These data included
      age, gender, diagnosis, race and whether the patient was enrolled on an open
      treatment study. Univariate analyses were carried out to compare demographic data
      between AYA patients (aged 15-22) who enrolled on study and those who did not.
      RESULTS: Eight hundred sixty-five new oncology patients were seen at CHP during
      this time, 23% of whom were 15 years or older; 33% of all patients were treated
      on a clinical trial, including 34% of younger patients and 24% of older patients
      (P = 0.0017). The differences between these rates and those from prior years in
      both age groups (38% and 27%, respectively) were not statistically significant (P
      = 0.15, 0.53). The most common reason for the low enrollment rates was again the
      lack of an open therapeutic trial. CONCLUSION: Despite initiatives at CHP and on
      the national level to enroll more AYA patients on clinical trials, our most
      recent data show no improvement. This is a potentially remediable factor that
      needs to continue to be prioritized nationally.

PMID- 28509441
TI  - The Greek Registry of Shwachman Diamond-Syndrome: Molecular and clinical data.
AB  - This study presents the clinical phenotype and molecular analysis findings from
      11 patients recorded in the Greek Shwachman-Diamond syndrome (SDS) Registry. The
      most severely affected patient in our registry was diagnosed at birth and is the
      first patient reported to require bone marrow transplantation so early in life.
      Severe psoriasis, a feature not previously reported in SDS, was observed in one
      patient. Mutations in the Shwachman-Bodian-Diamond syndrome gene (SBDS) were
      found in all patients. Cytogenetic analyses revealed clonal abnormalities, one
      novel, in two patients.

PMID- 28509442
TI  - Self-Assembled Nanoparticles from Phenolic Derivatives for Cancer Therapy.
AB  - Therapeutic nanoparticles hold clinical promise for cancer treatment by avoiding
      limitations of conventional pharmaceuticals. Herein, a facile and rapid method is
      introduced to assemble poly(ethylene glycol) (PEG)-modified Pt prodrug
      nanocomplexes through metal-polyphenol complexation and combined with
      emulsification, which results in ~100 nm diameter nanoparticles (PtP NPs) that
      exhibit high drug loading (0.15 fg Pt per nanoparticle) and low fouling
      properties. The PtP NPs are characterized for potential use as cancer
      therapeutics. Mass cytometry is used to quantify uptake of the nanoparticles and
      the drug concentration in individual cells in vitro. The PtP NPs have long
      circulation times, with an elimination half-life of ~18 h in healthy mice. The in
      vivo antitumor activity of the PtP NPs is systematically investigated in a human
      prostate cancer xenograft mouse model. Mice treated with the PtP NPs demonstrate
      four times better inhibition of tumor growth than either free prodrug or
      cisplatin. This study presents a promising strategy to prepare therapeutic
      nanoparticles for biomedical applications.

PMID- 28509443
TI  - Haemodynamically stimulated and in vivo generated axially vascularized soft
      tissue free flaps for closure of complex defects: Evaluation in a small animal
      model.
AB  - The arteriovenous (AV) loop model permits the creation of significant volumes of
      axially vascularized tissue that represents an alternative to conventional free
      flaps, circumventing their common limitations. However, such AV loop-based flaps
      have never before been examined in standardized animal models with respect to
      their suitability for reconstruction of critical bone-exposing defects. In the
      course of our preliminary studies, we implemented a novel defect model in rats
      that provides standardized and critical wound conditions and evaluated whether AV
      loop-generated flaps are suitable for free microsurgical transfer and closure of
      composite defects. We compared three groups of rodents with similar scapular
      defects: one received the AV flap, whereas controls were left to heal by
      secondary intention or with supplementary acellular matrix alone. To create the
      flaps, AV loops were placed into subcutaneous Teflon chambers filled with
      acellular matrix and transferred to the thigh region. Flap maturation was
      evaluated by histological analysis of angiogenesis and cell migration at days 14
      and 28 after loop creation. Flap transfer to the scapular region and
      microsurgical anastomoses were performed after 14 days. Postoperative defect
      closure and perfusion were continually compared between groups. Within the AV
      flap chamber, the mean vessel number, cell count and the proportion of
      proliferating cells increased significantly over time. The novel defect model
      revealed that stable wound coverage with homogeneous vascular integration was
      achieved by AV loop-vascularized soft-tissue free flaps compared with controls.
      In summary, our study indicates for the first time that complex composite defects
      in rats can successfully be treated with AV loop-based free flaps.

PMID- 28509444
TI  - [Demographic aspects of population aging in Saint-Petersburg at the end of XX-the
      beginning of XXI century. Part I. Conventional aging measures].
AB  - The paper represents the first part of the series of two articles on demographic
      aspects of population aging in Saint-Petersburg in 1990-2010 compared to the
      situation in the Russian Federation as a whole. In the first part, the situation
      with the population aging in Saint-Petersburg and Russia is considered based on
      traditional aging measures - the proportion of elderly in the total population,
      aging index, old age dependency rate and the parents support ratio. In the second
      part, a number of prospective aging indicators that take account of remaining
      life expectancy, will be studied. The analysis also includes the consideration of
      gender imbalance of aging indicators. Accelerating of population aging in Saint
      Petersburg and Russia leads to a new demographic situation requiring a number of
      economic and socially oriented measures.

PMID- 28509445
TI  - [Comparative assessment of aging rates in population from different cities].
AB  - 437 people (214 men and 223 women) at the age of 50-90 years old, residents of
      different cities of Russia and Pridnestrovie (Moscow, Barnaul, Tiraspol) have
      been examined. Using a complex of morphofunctional characteristics, parameters of
      the biological age have been analyzed, and groups with delayed, moderate and
      accelerated aging rates have been outlined. Regional peculiarities in
      distribution of incidence of different variants of aging rates have been
      revealed. In Moscow men and women, the delayed variant of development of age
      involution changes is the most widespread. In Tiraspol women, compared to the
      Moscow group, incidence of people with accelerated aging rates is 2 times higher,
      which can be stipulated by influence of a complex of biosocial factors.

PMID- 28509446
TI  - [Stochastic simulation of the process of matching of the ages of the human and
      the experimental mammalian].
AB  - The aim of the article is to work out the simple approach for matching of the
      ages of the human and mammalian. The model is based on the analysis of the
      counting processes of the proper ontogenetic events (such as the emergence of the
      first molars, the first ovulation, almost complete cessation of growth,
      menopause). The choice of the events is reduced to the claim of being observable.
      The matching (and proper concordance) are useful for the choice of the individual
      regimens of medical treatment.

PMID- 28509447
TI  - [Discontinuity of the annuity curves. I. Departures from Gompertz law in
      Drosophila melanogaster Canton-S strain].
AB  - Analysis of male imago mortality in Drosophila melanogaster Canton-S strain
      demonstrated deviation from Gompertz law. Annuity curves were composed of five
      phases divided by sharp bends. All the phases seemed to be linear. We discuss the
      hypotheses of strict genetic determination of the phenomenon.

PMID- 28509448
TI  - [Influence of changes in the reproductive behavior on the average duration of the
      reproductive period and life span].
AB  - This article explains the model of changing the duration of the reproductive
      period and life span under the influence of the demographic trend towards an
      increase in age at first birth in modern developed countries. Acting as a factor
      of artificial selection, increase parental age may lead to a shift of the upper
      boundary of the reproductive period in the new generations, and life expectancy.
      The article discusses the role of a number of social factors to identify trends.

PMID- 28509449
TI  - [Modern directions of scientific and practical research of the policy of active
      and healthy longevity: experience and perspectives].
AB  - Modern terminology on active and healthy aging used in scientific and project
      activities is discussed. There have been analyzed the WHO conception on active
      aging, which has no precise universally agreed definition, its main determinants.
      The directions of scientific expertise in the major European projects INNOVAGE -
      assessment of potentially profitable social innovations relating to the welfare
      and quality of life and health in old age; MOPACT - the interference between the
      demographic development and the main dimensions of economic and social
      contribution of older persons is defined. The approach to implement the policy of
      active and healthy longevity as a valuable asset of the modern society is
      underlined.

PMID- 28509450
TI  - [Socio-psychological grading in gerontology].
AB  - Senior and senile age is characterized by psychological, social and somatic
      heterogeneity of patients. To ensure high level of quality of life and to
      optimize the functioning of staff of geriatric hospitals we propose to introduce
      the distribution of pensioners within departments based on their psychosomatic
      status. On the analogy of the "medical triage", authors propose to introduce
      socio-psychological grading of older persons living in geriatric centers,
      focusing on their ability for self-care, the degree of preservation of cognitive
      functions, individual psychological characteristics. Testing of this grading was
      made on the basis of the Scientific and Methodological Gerontological Center. As
      a result of introduction of the principle of socio-psychological grading,
      positive dynamics in the psychological state of patients, better performance of
      the staff, and improved subjective assessment of the quality of life of older
      persons were registered.

PMID- 28509451
TI  - [Physiological aspects of music and longevity].
AB  - The article provides an overview of the results of studies on the effect of music
      on the function of various physiological systems of the organism including the
      nervous, cardiovascular and endocrine systems, also on the effect of Mozart's
      music and the later mature Baroque music. Particular attention is paid to
      information on the influence of different kinds of music (classical, jazz and
      rock), of the nature and of the degree of musical activity (listeners, amateurs
      and professional performers) on cognitive and behavioral function, on health
      status, life expectancy and longevity. Structural acoustical attributes of music
      defining its treatment effect, are described with the comparison of aspects of
      rock music and of classical music. The article also considers the prospects for
      using of music in the treatment and prevention of age-associated diseases.

PMID- 28509452
TI  - [Adhesion molecule JAM-A, its function and mechanism of epigenetic regulation].
AB  - The article represents evidence about structures, properties and functions of
      adhesion molecule JAM-A/1 belonging to JAM subfamily. This protein plays an
      important role in epithelial tight junction formation and immune function.
      Current article focuses on the role of JAM-A protein in pathogenesis associated
      to ageing: atherosclerosis, apoplexy, thrombosis, hypertension, ophthalmological
      pathology. We propose short peptides Lys-Glu, Lys-Glu-Asp, and Ala-Glu-Asp-Gly
      could influence on F11R gene expression that leads to recovery of JAM-A synthesis
      in cells.

PMID- 28509453
TI  - [Central female hypogonadism as a model of premature aging].
AB  - Central (hypogonadotropic) hypogonadism in women could also be a cause of
      persistent amenorrhea and hypoestrogenemia. The aim of this study was to evaluate
      symptoms of premature aging in women of young age with central hypogonadism. 88
      young women (25 [21; 30] y.o.) with central hypogonadism (with isolated
      hypogonadotropic hypogonadism n=42, and associated with the other types of
      pituitary insufficiencies n=46), 53 healthy young women (24 [23; 28] y.o.) and 50
      healthy postmenopausal women (56 [53; 58] y.o.) were examined. In young women
      with central hypogonadism frequency of psychoemotional, neurovegetative and
      urogenital disorders, peripheral sex steroid concentrations, lipid and mineral
      homeostasis parameters differed significantly from the healthy young women of
      similar age and were comparable with postmenopausal women of middle/older age.
      Thus, according to clinical, hormonal and biochemical abnormalities biological
      age of female patients with central hypogonadism advanced significantly
      chronological young age and corresponded to middle/older age. The central female
      hypogonadism is a model of premature aging.

PMID- 28509454
TI  - [Monoamine oxidase activity in rat pineal gland: comparison with brain areas,
      alteration during aging].
AB  - Using benzylamine as a substrate, the amine oxidase activity was determined in
      the pineal gland of adult rats and compared with the same activity in brain areas
      and pituitary. Two groups of rats aged 6-8 and 14-15 months were also compared on
      the basis of this activity. Benzylamine deaminating activity in the pineal gland
      was significantly higher than in the area preoptica medialis, the corpus
      mamillare, the tuberculum olfactorium, and the hypophysis, and lower than in the
      eminentia mediana. The significant increase of the activity in the pineal gland
      in animals of age from 6-8 to 14-15-months was revealed. Benzylamine deaminating
      activity in the pineal gland was totally inhibited by 0,002 mM R deprenyl,
      indicating the B type monoamine oxidase (MAO B) activity. Age-associated increase
      of MAO B activity in the pineal gland accompanied by decrease of glutathione
      peroxidase activity, reported earlier, can promote the oxidative damage in the
      pineal gland during aging.

PMID- 28509455
TI  - [Transport function of the lymph nodes in young and old animals].
AB  - The paper discusses the age-related changes of contractile activity of the
      capsule of the lymph nodes, underlying their transport function. The results of
      the studies conducted on the mesenteric lymph nodes of young and old bulls are
      presented. The changes in the contractile function of the capsule of the lymph
      nodes were revealed in the older animals. The changes appeared in the decrease of
      the amplitude and increase of the phase contraction frequency which are based on
      the replacement of smooth muscle by connective tissue, the enhancement of
      pacemaker activity of smooth muscle cells and endothelial dysfunction of lymph
      node cells.

PMID- 28509456
TI  - [The morphological changes of Hassall corpuscles of the different maturity in
      vertebrate animals and human in different stages of age].
AB  - With the use of methods of light microscopy we produce comparison morphological
      investigation of Hassall corpuscles of different maturity in animals and human
      with age difference. It was arranged that quantity and sizes of Hassall
      corpuscles in different stages of age depend on organization level, belonging to
      a vital form, shape and age of animal. On the base of our investigation we can
      make resume about functional role of Hassall corpuscles.

PMID- 28509458
TI  - [Melatonin in a woman's life: from birth to menopause].
AB  - We did a review of the literature data of main Russian publications and databases
      PubMed/Medline for the last 7 years. In the present article we examine the
      physiology of secretion of pineal hormone melatonin and its role in the vital
      processes of the body. The study was focused on the influence of melatonin on the
      female reproductive system, participation in the aging process and the formation
      of pathological menopause. The article presents research data on the
      effectiveness of the drug melatonin in the climacteric syndrome. It is revealed
      that up to the present time according to the literature data there is no
      information about the standards of secretion of melatonin for women of different
      age groups, and the lack of secretion of melatonin can be judged by clinical
      manifestations, and also when compared with groups of healthy women. Remain
      unclear issues in the application of drugs melatonin at various complications of
      pregnancy and gynecological diseases. Long-term use of melatonin is still open in
      climacteric syndrome.

PMID- 28509457
TI  - [Urine proteome study for the evaluation of age dynamics in healthy men].
AB  - We investigated the age dynamics of proteomic profile of urine in 52 healthy men
      aged 18 to 51 years. A special sample preparation was performed, followed by
      liquid chromatography-mass spectrometry. Liquid chromatography-mass spectrometry
      of the minor proteins was performed on a nano-HPLC Agilent 1100 system ("Agilent
      Technologies Inc.", USA) in combination with a LTQ-FT Ultra mass spectrometer
      ("Thermo Electron", Germany). A total of 259 proteins were identified. According
      to the TiGER database, a tissue origin was established for 141 proteins and
      identified 715 processes in which they participate. We found a significant
      positive correlation with age, the number of proteins (R=0,566; p-value=1,24E-05)
      and the weight of proteins (R=0,45; p value=8,17E-04). Identified 23 proteins
      were significantly more frequent in the urine of subjects with increasing age
      (p<0,05), and only one protein - RGSL, Regulator of G protein signaling protein
      like (MW 125.69) - less frequently.

PMID- 28509459
TI  - [Subclinical hypothyroidism in elderly people].
AB  - In this review, we discuss clinical features of subclinical hypothyroidism in the
      elderly. The article describes the current diagnosis and treatment modalities of
      subclinical thyroid dysfunction in the older age group.

PMID- 28509460
TI  - [Changes in serum hormone levels in the middle and gerontic aged inhabitants of
      Arkhangelsk due to the gender identity].
AB  - The serum hormone levels were studied among middle and gerontic aged residents of
      Arkhangelsk by enzyme immunoassay and radioimmunoassay. The significant increase
      of follicle-stimulating and luteinizing hormones levels in gerontic aged men was
      recorded in the presence of higher concentrations of these hormones in women.
      There was a statistical tendency of decrease in the level of testosterone in
      gerontic aged women compared to middle aged. Regardless of gender the lowering of
      the dehydroepiandrosterone sulfate content was observed in gerontic aged
      residents compared to middle aged. The criteria of functional activity reduction
      of the thyroid gland were a decrease in serum free thyroxine fraction levels in
      gerontic aged women and low concentrations of common triiodothyronine in middle
      aged men living in Arkhangelsk. Serum cortisol, insulin, estradiol, growth
      hormone had no significant age and sex differences in the present groups. The
      number of correlations was greater among the gerontic aged people in comparison
      with the middle aged, especially among women.

PMID- 28509461
TI  - [Age and gender aspects of the status of lipid profile and stress-realizing
      systems of the human body in the aging process].
AB  - In the course of inspection 1136 persons of different age and sex data on
      dynamics of the main components of lipid profile, the concentration of brain
      derived neurotrophic factor (BDNF) in blood plasma and indicators of levels of
      free cortisol, melatonin sulfate, metanephrine and normetanephrine in urine daily
      were obtained. Clear age and gender differences related both to the content of
      atherogenic fractions of lipids in the blood, and types of dyslipidemia were
      revealed. Fundamental differences in the age dynamics of indicators of stress
      realizing systems in men and women and the correlation of these indicators with
      the level of low density lipoproteins and atherogenic coefficient were
      identified. The data obtained may indicate different mechanisms of development of
      atherosclerosis and its associated pathological aging in people of different sex
      and age, which enables the practical use of research results for the earliest
      diagnosis and prognosis of a number of associated with age and pathological
      conditions.

PMID- 28509462
TI  - [Musculoskeletal system as a target organ of a frailty processes].
AB  - Pathology of the musculoskeletal system is widespread in the population and is
      one of the most common diseases of patients in older age groups. The most
      significant of them are osteoporosis, osteoarthritis and sarcopenia. All three
      components separately, of course, lead to lower quality of life. In our work we
      show the mechanisms of interference of these states at each other, and their
      combined impact on the musculoskeletal system as a target organ processes senile
      asthenia. Osteoarthritis, osteoporosis, and sarcopenia, and especially their
      combination lead to hypomobility. Hypomobility under the influence of external
      factors is one of the leading syndromes potentiating aggravation processes senile
      asthenia. Thus, the mechanism of re-entry is triggered, and a vicious circle
      leading to fatal medical-social and social consequences. It is shown that changes
      in the musculoskeletal system should be considered as a single aging within
      senile asthenia, and all used and newly created medical and social rehabilitation
      and prevention programs should be integrated in nature.

PMID- 28509463
TI  - [Short and medium-term variability of blood pressure in elderly patients with
      arterial hypertension and predicting the risk of renal dysfunction].
AB  - The aim of the work was to specifically identify short and medium variability of
      blood pressure (BP) in elderly patients with arterial hypertension and to
      evaluate the prognostic value of fluctuation of BP for the development of renal
      dysfunction. 64 patients with hypertension were surveyed: a core group of 33
      patients with start-AG over the age of 60 years, the control group - 31 patients
      with uncomplicated hypertension and onset before the age of 60 years. Variability
      was evaluated by day, night and diurnal SBP and DBP according to the results of
      daily monitoring of blood pressure, as well as intra-individual (short-term) and
      visit-to-visit blood pressure variability (seven consecutive days) (medium-term).
      The relationship between the parameters of variability of BP and the
      characteristics of chronic kidney disease was studied. The elderly hypertension
      patients demonstrated a higher short-term and medium-term variability of BP.
      Increasing medium variability of systolic BP in advanced aged patients is
      associated with the development of chronic kidney disease. When the medium-term
      variability of systolic BP exceeds the level of 9,7 mm Hg, the risk of developing
      chronic kidney disease increases with a diagnostic sensitivity of 77,1 % and
      diagnostic specificity of 80,8 %.

PMID- 28509464
TI  - [Features of memory and intellectual activity among the elderly with different
      reading productivity].
AB  - The aim of this work was the study of indicators of memory and intellectual
      activity among the elderly with different reading productivity. The results of
      the study showed that the elderly were distinguished by a greater number of
      errors when performing tasks on oral-aural, visual memory and visual-spatial
      activities. The mistakes made by subjects with low reading productivity may
      indicate dysfunction of tone and wakefulness, of receiving, processing and
      storing information, as well as weakening of hemispheric interaction.

PMID- 28509465
TI  - The evaluation of cognitive skills and the quality of life between Parkinson
      Disease patients and healthy aged people above 60 years old.
AB  - In the 21st century mankind has made a huge progress in the health care system,
      so the average life expectancy has increased significantly compared to the
      previous centuries. The managing of healthy ageing of the population represents
      one of the main actual problems of the national health care systems around the
      world as the aged population is increasing, so, for instance, it is estimated
      that there will be over 2 billion people worldwide over the age of 65 by the year
      2050 [36]. In particular, the age-related neurological diseases such as Parkinson
      Disease (PD) have seen a dramatic increase in international prevalence.
      Projections suggest that the neurodegenerative diseases like PD will surpass
      cancer as the leading cause of death by the year 2040 [36]; thus presenting an
      ever-growing challenge to maintain an optimal quality of life of the patients. In
      healthy ageing, cognitive skills impair naturally due to natural brain atrophy;
      in PD these processes are rather accelerated, so that, overwhelming clinical
      studies showed that dementia eventually develops in up to 80-85 % of patients
      with PD [1, 39]. This article is focuses on evaluating the health related quality
      of life measurements of PD patients such as cognitive status, anxiety and stress
      levels as well as it aims to suggest a possible future strategy to improve the
      quality of life of the patients.

PMID- 28509466
TI  - [The DC-potential of the brain in older women with postural instability].
AB  - The article presents the results of studies of the DC-potential of the brain
      level distribution in elderly women with postural instability. Analysis of the DC
      potential of the brain level distribution was held by mapping obtained by
      measuring the monopolar values of the DC-potential of the brain and calculating
      deviations in each of the leads from the average records which were registered in
      all areas of the head. It is established that elderly women with postural
      instability DC-potential of the brain level distribution are characterized by
      increasing in background values and rigid structure of the interaction between
      brain regions. The disturbance of the principle of the dome-shaped DC-potential
      of the brain level distribution due to the alignment of values for brain regions
      was revealed. Factor model with postural instability reflects the control
      strengthening over the potential falls from the frontal areas of the brain.

PMID- 28509467
TI  - [Age characteristics of the cardiovascular system, depending on the thyroid
      function in type 2 diabetes mellitus].
AB  - To study the features of cardiovascular system in patients with diabetes mellitus
      type 2 considering the thyroid pathology and age, 264 patients were examined.
      They were divided into three groups: 1st - patients with diffuse-nodular changes
      in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a
      control group of patients without thyroid disease. The patients of different ages
      were examined in each of these groups. All patients were in euthyroid state. It
      was established that identified in diabetes mellitus type 2 thyroid pathology and
      the thyroid disease contribute special features to the clinical picture for
      combined diabetic and cardiovascular pathology even in a euthyroid state
      including the age features. The laboratory and instrumental researches showed
      that the patients with combined diabetes and thyroid pathology have a higher
      incidence of atrial fibrillation, ischemic heart disease, and ventricular
      arrhythmias of high grades. They also were noticed to have a more adverse form of
      the left ventricle remodeling, also the combination of diastolic and systolic
      dysfunctions were found to be more frequent. It was concluded about the necessity
      of early diagnosis and correction of the cardiovascular disorders and thyroid
      systems in type 2 diabetes mellitus patients, including euthyroid patients.

PMID- 28509468
TI  - [Age-related changes of the content of angiomatin and endostatin in human skin].
AB  - Human skin structures stained positively for angiomotin or endostatin were
      studied by indirect immunohistochemical method. Skin specimens from frontal
      surface of the lower part of the neck (from upper corner of standard autopsy skin
      incision) from human fetuses died antenatally from 20 to 40 weeks of pregnancy,
      humans who died from different causes from 1 day to 85 years of life were
      obtained at autopsy. Positive staining for angiomotin or endostatin in the skin
      was found in epidermal cells, fibroblasts, sweat and sebaceous glands, blood
      vessels of the dermis. Blood vessels stained positively for angiomotin were
      detected in skin samples in all ages. Age-dependent decrease in the content of
      angiomotin in blood vessels of the dermis was detected. Most prominent decrease
      in angiomotin content in dermal blood vessels was found in 61-85 years age-group.
      Endostatin positive blood vessels were also detected in skin samples of all ages.
      However, the intensity of staining for endostatin in dermal blood vessels was
      increased during aging. It can be proposed that changes in the content of
      angiomotin and endostatin yield a negative impact on angiogenesis in human skin
      during aging.

PMID- 28509469
TI  - [The review of the peptides used in dermatocosmetology].
AB  - The review of the peptides used in dermatocosmetology is represented. The purpose
      of this review is a search of results of the basic scientific researches
      confirming or disproving efficiency and/or safety of peptide molecules used in a
      modern dermatocosmetology. Questions of forms of application, biological
      availability, reliability of the rendered anti-aging effects are considered.

PMID- 28509470
TI  - [Treatment of elderly patients with combination of coronary artery disease and
      aortic valve pathology].
AB  - Increasingly, there are patients with concomitant coronary artery disease and
      aortic valve, especially in elderly patients, who often have severe comorbidities
      and high surgical risk, which is undoubtedly a certain effect on the choice of
      method and tactics of treatment. Today, there are several approaches to the
      treatment of patients in this category, and all of them have certain advantages
      and disadvantages.

PMID- 28509471
TI  - [The study of general satisfaction in stationary social institutions (Yaroslavl
      Regional Gerontology Center)].
AB  - The article analyzes the satisfaction with social environment of patients of
      older age groups living in the Yaroslavl Regional Gerontology Center. On the
      basis of a survey of 118 patients of older age groups the satisfaction with the
      living conditions in the institution, the provision of socio-medical assistance,
      catering, leisure activities and social environment were assessed. 92,4 % of
      patients reported of their satisfaction, in general, with the stay. The obtained
      information confirms necessity of creation of qualitative therapeutic environment
      in a hospital of social service.

PMID- 28509472
TI  - [Analysis of indicators of primary disability due to cerebrovascular diseases in
      people of retirement age according to the results of medical and social
      examination in St. Petersburg].
AB  - The article presents data on the primary disability due to cerebrovascular
      disease in elderly patients based on the results of the survey in the Bureau of
      Medical and Social Expertise of Saint-Petersburg from 2005 to 2014. The analysis
      showed a reduction in the indicators of primary disability due to cerebrovascular
      disease and the increase in the share of persons with disabilities of the first
      and third groups in its structure.

PMID- 28509473
TI  - [The issue of quality of Russian cause-specific mortality statistics at old
      ages].
AB  - The paper presents a brief analysis on the quality of cause-specific mortality
      statistics at old ages in Russia. Two aspects are in focus: the regional
      differences in approaches for choosing the underlying cause of death and the
      comparison of Russian coding practice with the practices of some other European
      countries. The results obtained indicate that there are certain problems with the
      quality of cause-of-death coding at old ages in Russia. No unified approach to
      coding deaths as caused by "Senility" is used at a sub-national level. This leads
      to the distortion of the regional cause-specific mortality structures.
      Furthermore for many groups of causes Russian death rates are much lower than
      those in European countries. This peculiarity is caused by the specificity of
      Russian cause-of-death coding practice, which results in underestimating the
      mortality from certain causes at old ages.

PMID- 28509474
TI  - [The season of birth and mortality (Based on workers mortality epidemiological
      study materials)].
AB  - The article presents a comparative assessment of the death absolute risk for the
      humans born in different seasons and months of the year based on the
      epidemiological studies found on the retrospective cohort for the 40 years period
      (the end of the 20th-beginning 21st century). It is shown that mortality of
      people born in January-February differ from similar parameters of persons born in
      March-April.

PMID- 28509475
TI  - [About expedience and perspectives of immortalism].
AB  - The human environment is subjected to changes due to anthropogenic activity. It
      will change in future as well. To survive, the human population should
      genetically be reorganized according to these changes. This requires an
      alternation of generations. The mechanism of senescence is not atavism from which
      we should escape but the achievement of evolution without which the humanity
      cannot exist.

PMID- 28509476
TI  - [Temporal order deterioration and circadian disruption with age. 2. Systemic
      mechanisms and correction].
AB  - Part 2 of the present review highlights the impact of aging on mechanisms
      involved in response of the circadian system to different photic and non-photic
      factors, especially zeitgebers. Promising strategies to prevent age-dependent
      circadian disruption using internal and external factors that may entrain
      circadian rhythms are presented. In particular, benefits of bright light,
      melatonin and other chronobiotics, the circadian body temperature rhythm,
      physical activity and regular feeding schedules to preserve the temporal order of
      aged organisms are discussed, emphasizing especially a personalized approach
      based on the assessment of individual overt rhythms parameters.

PMID- 28509477
TI  - [Neurocomputer identification of order parameters in gerontology].
AB  - Investigation of distinctions discovered between three groups of different age
      female-khanty (indigenous population of Ugra, Russia) of five active components
      (from all 14 components registered) of a state vector of cardiovascular system
      shows the wrong solving binary classification problem in a five dimensional phase
      space by one iteration or a few iterations p (p<=50) using a neuroemulator. We
      prove that solving binary classification problem by a neuroemulator must be
      repeated about 1 000 times since it provides identifying more significant
      diagnostic signs xi between two significant figures after comma which exhibit the
      significance in diagnostics of aging rate (this is system synthesis problem
      solving in gerontology).

PMID- 28509478
TI  - [Telomere length, telomerase activity, stress and aging].
AB  - The review is dedicated to analysis of data available at present time concerning
      possible influence of stress upon telomere lengths and telomerase activity, as
      well as various ways of counteracting it. Present-day telomerase theory of aging
      gains a new impetus, shedding light upon the influence of psychological state of
      humans and their ability to counteract stress, upon the process of aging. It also
      tends to regard telomere shortening and the decrease in the activity of
      telomerase as a marker of level of the ability to adapt to both inner and outer
      influences. Both aging and age-dependent diseases are proved to be substantially
      retarded not only by the administration of drugs, but also by psychological
      means, which forms a good way towards healthy longevity. With complete
      understanding of the impossibility to prevent or even to slow down natural
      senescence itself, these methods allow to remove causes, which accelerate
      senescence, and to increase the average human longevity.

PMID- 28509479
TI  - [Study of gene expression of transcription factors T cells during aging].
AB  - The level of expression of transcription factor genes (GATA-3, TBX21, IL23A), and
      changing of oxidative modification of proteins in young and elderly healthy
      persons was studied. The results of evaluation of gene expression, GATA-3 in
      lymphocytes showed the increased expression of GATA-3 in elderly people in
      comparison with the young. Women demonstrated higher expression of GATA-3 in
      compare with men. Study of IL-2p showed reduced levels of expression in aged
      humans compared to young. TVH21 expression level showed a reduction expression in
      both men and women. Comparative analysis of protein oxidation in blood plasma of
      young and elderly people showed an increase in the intensity of oxidative
      modification of proteins in the elderly.

PMID- 28509480
TI  - [Signal molecules of endometrium: gerontological and general pathhological
      aspects].
AB  - The review describes neuro-immuno-endocrine signal molecules expression in human
      endometrial cells in the normal conditions, in the pathology and during aging.
      Human endometrial cells synthesizes estrogen, progesterone, estradiol, progestin,
      cell adhesion molecules (integrines alpha1beta1, alpha4beta1, alphaVbeta3, L
      selectin, E-catgerin, MUC1), grow factors (TGF, EGF, HB-EGF, IGF), cytokines (IL
      1, IL-2, INF-alpha, IL-12, SXSL10, CXCL11, CXCR3), various immune cells markers
      (CD68, CD105, CD163, CD16, CD56, CD4, CD8), heat shock proteins (HSP60, HSP70,
      HSP90, VEGF, MMP). Changes of this molecules expression level are the base of the
      social significant diseases as endometriosis, endometrial cancer and infertility.
      Thus, the investigation of neuro-immuno-endocrine interactions in endometrial
      cells can be used for new drugs creating, in differential diagnostics of
      endometrial cancer and increasing of extracorporal fertilization success.

PMID- 28509481
TI  - [The type of age-related cataract as available marker of socially significant
      diseases of the organism].
AB  - The aim of the research was to investigate the general somatic status and to
      investigate the influence of dominating part of vegetative nervous system,
      following the different types of senile cataract formation in human. Thus, the
      domination a sympathetic nervous system and correlated systemic dystrophic
      changes of the tissues in patients with cortical cataract have been found for the
      first time. Moreover, patients with nuclear cataract had the domination of
      parasympathetic nervous system and another character of dystrophic changes.
      Therefore, the type of a forming age-related cataract can be offered as an
      available clinical marker of character of neurodystrophic process occurring in an
      organism.

PMID- 28509482
TI  - [Age-related changes in blood microcirculation functional state of the brain
      cortex of rats].
AB  - Male Wistar-Kyoto rats, aged 22-24 months, were intracerebrally transplanted
      syngeneic mesenchymal stem cells (MSC). Cognitive functions of these animals were
      tested in 3 weeks. The density of microvascular bed, the tissue blood flow,
      saturation of mixed blood in cortex microvessels were measured under the standard
      conditions, under the impact of noradrenaline and in the context of global
      ischemia. The control groups consisted of rats aged 2-3 months and 22-24 months.
      MSC transplantation have a positive impact on the microcirculation in brain
      cortex of old animals: reduction of vascular density was prevented, level of
      saturation in the blood vessels was increased, which enabled animals to endure
      easier extreme impacts, but did not correct age-related deterioration of
      cognitive functions.

PMID- 28509483
TI  - [The influence of hyperhomocysteinemia on monoaminoergic systems of hypothalamus
      and hippocampus of female rats at aging].
AB  - The data presented have shown the different effect of hyperhomocysteinemia
      (induced by 0,12-0,15 mg of methionine loading per os during 30 days) on
      monoamines content in hypothalamus and hippocampus of young (6-7 month) and old
      (20-22 month) female rats. It has been established that the level of
      catecholamines (noradrenaline, dopamine), 5 oxitryptamine and 5 oxyindolacetic
      acid in hypothalamic areas responsible for synthesis and secretion of
      gonadoliberin (medial preoptic area and medial eminence with arcuate nuclei) is
      considerable less in old animals compared with young ones. These data are in
      agreement with the low content of gonadoliberin found by us in medial eminence
      with arcuate nuclei. It has been also shown the decreased level of monoamines
      level in hippocampus of old rats, which does not depend on methionine loading.
      However in hippocampus of young animals hyperhomocysteinemia induced a noticeable
      reduction of noradrenaline and 5 oxyindolacetic acid, which can lead to weakening
      of animal's cognitive function.

PMID- 28509484
TI  - [Neuropsychological changes in cognitive function during the transition of the
      elderly in old].
AB  - The goal is to track changes in psychophysiological characteristics of cognitive
      functions associated with the transition of the elderly in the senile. 46 elderly
      people with a mean age of 70,5+/-1,7 years were surveyed. After 7 years remaining
      25 people were re-examined. The method of time estimation of right - and left
      brain reactions to various stimuli - visual, auditory, and cutaneous signals at
      rest and on the background of mental stress was applied. In non-survived subjects
      in the initial survey the indicators of right- and left-brain reactions were
      delayed, further slowing in response to mental stress, while survivors' reactions
      of both hemispheres were very active, and the mental load caused activation of
      both hemispheres. Re-examination of survivors conducted after 7 years has
      revealed they slow right- and left-brain reactions, while the mental load caused
      them already noticeable inhibition of the left hemisphere. Identified in the
      study positive correlation of cognitive resource in old age with survival of the
      individual to the senile age should be regarded as a manifestation of the
      physiological relationship of integrative properties of the brain and organism
      viability in ontogenesis. In this regard, the state of reactivity of the sensory
      areas of the brain can be considered as one of the indicators of the prognosis of
      survival of a person under a certain age.

PMID- 28509485
TI  - [Clinical and pathogenetic features of ischemic stroke among representatives of
      different gender and age].
AB  - We observed 1410 patients of different gender and age with ischemic stroke of 4
      main clinical and pathogenic types - atherothrombotic, cardioembolic, hemodynamic
      and lacunar. The dependence of the pathogenic type of stroke, background options
      for stroke pathology and risk factors of stroke on sex and age of patients was
      analyzed. We founded out that atherothrombotic ischemic stroke is more common for
      persons of retirement age, and in working paeople - gap and hemodynamic once,
      although atherothrombotic strokes in this age group were more frequently observed
      among men. The importance of hypertension in the development of ischemic stroke
      reduces with age, but the role of cerebral atherosclerosis, ischemic heart
      disease and cardiac arrhythmias increases. As risk factors for ischemic stroke in
      the pension age physical inactivity, overweight and dyslipidemia play the main
      role, when reducing the role of smoking and stress, more relevant for working
      people. The frequency of the presence of certain risk factors and background for
      ischemic stroke disease depends on the patient's gender, but in different age
      periods and under different pathogenic types of ischemic stroke this dependence
      changes and in people of retired age it is less distinct than in working people.

PMID- 28509486
TI  - [Early diagnosing of delirium in the elderly with acute stroke].
AB  - Delirium is a common complication of stroke worsening its prognosis. The aim of
      the work is to identify the group of risk for the development of delirium among
      elderly patients with acute stroke and assessment of diagnostic value of 4-A test
      in identifying delirium in this category of patients. We included 73 patients in
      the study, 33 (45 %) of which had symptoms of delirium according to DSM-IV.
      Patients with delirium had more severe neurological deficit, more prominent
      chronic changes on brain CT, more often had positive axial reflexes, had higher
      erythrocyte sedimentation rate. All patients with pneumonia were delirious.
      Russian version of 4-A test showed good psychometric properties. Thus the risk of
      the development of delirium in older adults with acute stroke is higher among
      patients with severe strokes, more prominent chronic changes in the brain
      according to CT and clinical examination and in those with inflammatory
      complications. Purposeful screening of the patients with aforementioned risk
      factors with instruments such as 4-AT will allow more efficient and fast
      diagnosing of delirium on early stages in the elderly with acute stroke.

PMID- 28509487
TI  - [Evaluation of pharmacotherapy with perindopril, lozartan potassium and its
      combination in elderly patients with chronic heart failure].
AB  - To assess the pharmacotherapy of elderly patients with chronic heart failure
      (CHF), by studying the effect of perindopril, lozartan potassium and their
      combination on the severity of clinical symptoms, hemodynamics, exercise capacity
      and heart morphofunctional parameters, 78 patients with chronic heart failure II
      IV FC (for classification NYHA), complicating the course of coronary heart
      disease (CHD) with left ventricular ejection fraction <=45 % were examined. Men
      were 42 (53,8 %), women - 36 (46,2 %), mean age 64,8+/-3,7 years. The study
      revealed that the background as long-term monotherapy with perindopril and
      lozartan potassium in patients with CHF complicating CHD, CHF FC decreased
      significantly and significantly increased left ventricular ejection fraction (p <
      0,05). The combined treatment with perindopril and lozartan potassium showed no
      advantage over monotherapy with these agents. These patients showed a decrease in
      the frequency of angina attacks by 28,5 and 27 % respectively (p < 0,05) only
      after a long course of treatment with perindopril and the combination of
      perindopril and lozartan potassium.

PMID- 28509488
TI  - [Metformin reduces the signs of sarcopenia in old OXYS rats].
AB  - The increasing prevalence of sarcopenia (with the gradually aging population)
      necessitates the development of effective prophylactic strategies. As promising
      geroprotectors that comprehensively influence the processes of aging, mimetics of
      caloric restriction are being actively studied, for example, the antidiabetic
      agent biguanide Metformin (MF). We tested the influence of MF on the signs of
      sarcopenia in senescence-accelerated OXYS rats during oral administration (100 or
      300 mg per kilogram of body weight per day, with feed) from age 19 to 24 months:
      the period when the signs of sarcopenia are present. We analyzed the effects of
      MF on muscular strength of the rats and on structural and functional parameters
      of skeletal muscle by means of light microscopy. MF slowed down the age-related
      atrophy of muscle fiber bundles because it slowed the necrosis of some fibers,
      sclerotic changes in skeletal muscle, and hypertrophy of connective tissue of the
      perimysium (with a greater effect on the endomysium). MF also substantially
      improved the blood supply and metabolism in the fibers. As a result of MF
      treatment, the structure of skeletal muscle of OXYS rats approached that of
      Wistar rats (healthy control) in terms of qualitative and quantitative
      parameters; this improvement increased the muscle strength of OXYS rats and
      abrogated the weight loss that is characteristic of old age.

PMID- 28509489
TI  - [Assessment of work ability index in evaluation of small peptides geroprotective
      effect].
AB  - We have conducted a comparative analysis of the work ability index (WAI)
      application in evaluation of the effectiveness of small peptides (cytogens) used
      as geroprotectors in the system of preventive medical nutrition of those working
      with occupational hazards. Our study revealed the necessity of an inclusion of
      small peptides into the system of preventive medical nutrition, health promotion
      in people working with occupational hazards and thus subjected to an accelerated
      aging. The combined application of peptide geroprotectors makes it possible to
      restore and enhance adaptive resources as well as to correct work ability and
      maintain health and well-being in different professional groups.

PMID- 28509491
TI  - [Increase of drainage and immune functions of the lymph node as a factor of
      endoecological well-being in elderly and senile age].
AB  - Age-related changes in mesocolic lymph node reflect the general process of
      ageing. In lymph node, these changes are associated with size reduction of
      structural and functional areas in the setting of manganese excess and iron,
      zinc, and selenium deficiency, which determines the reduction of lymphoid tissue
      functional activity in elderly and senile ages. We have realized the idea to
      control the lymphatic system functions using phytotherapy. Phytotherapy provides
      improving drainage, detoxication, and immune function of the lymph node by
      increasing the size of functional compartments, intensification of
      lymphoproliferative processes and mitigating the deficiency of the main trace
      elements. The identified lypmhotropic effects of phytotherapy are interconnected
      with endoecological well-being factor and the increase of nonspecific body
      resistance in late ontogenesis. This result is of practical importance for the
      optimization of endoecological rehabilitation.

PMID- 28509490
TI  - [Postural control characteristics in elderly women with fallers].
AB  - Using computer posturografic (stabilometric) complex a study of postural control
      peculiarities was carried out in 108 women aged 65-74 years who had experienced
      two or more falls during the year (fallers). These tests were: Sensory
      Organization Test, Motor Control Test, Rhythmic Weight Shift. It was found that
      elderly women with fallers had a decrease of sensory information (somatosensory -
      by 1,8 %, of the visual - by 6 %, and of the vestibular - by 10,1 %), the
      neurophysiological mechanisms of postural control (by 5,7 points), violation of
      adaptation possibilities of sensory and motor components of the legs to respond
      quickly to changes in the center of gravity within the support base of its
      footing (7,3 ms), as well as reducing balance control in the frontal (by 7,2 %)
      and sagittal (by 23,2 % ) planes compared with the women of the same age without
      fallers.

PMID- 28509492
TI  - [Suitable working conditions for elderly people with different degrees of
      compensation of dysfunctional blood circulation of eyes].
AB  - In dealing with complex problems in labor and social rehabilitation of elderly
      people with different degrees of compensation of dysfunctional blood circulation
      of eyes, a great role play methods of rational and qualitative analysis of
      appropriate employment. The analysis of 110 patients of 55-70 years of age (220
      eyes) with dysfunctional blood circulation of eyes has been done. Professional
      abilities of elderly patients with dysfunctional blood circulation of eyes depend
      on the state of functioning vision and the level of blood circulation of the eye.
      In our study we show the clinical and prognostic data and based on that we could
      develop the absolutely prohibited working conditions depending on the level
      dysfunctional blood circulation of eyes of elderly people.

PMID- 28509494
TI  - [Influence of age and degree of compensation of carbohydrate metabolism on
      metabolic changes in blood of women patients with type 2 diabetes].
AB  - The purpose of this study was a comprehensive analysis of various aspects of
      metabolism of erythrocytes in women with type 2 diabetes, according to the age
      characteristics of compensation of carbohydrate metabolism. The obtained results,
      based on the nature of changes in parameters of carbohydrate and energy
      metabolism, gas transport and antioxidant systems of blood, contribute to the
      understanding of the role of metabolic changes in red blood cells, leading to
      changes in their biological properties, severity of which reflects the adaptive
      capacity of the organism in terms of hyperglycemia in different age groups in
      type 2 diabetes.

PMID- 28509493
TI  - [Pinealon and Cortexin influence on behavior and neurochemical processes in 18
      month aged rats within hypoxia and hypothermia].
AB  - The research of Cortexin and Pinealon within two models of stress, acute
      hypobaric hypoxia and mild hypothermia, within 18-month aged rats has been held.
      The peculiarities of peptide preparations' influence on behavior and
      neurochemical indeces have been identified. Cortexin shows a more pronounced
      effect on free radical processes and caspase 3 activity in brain than Pinealon.
      Both preparations forward an accumulation of adrenergic mediator within rats'
      brains in the model of acute hypobaric hypoxia, as well as serotonin within
      cerebrum cortex in the model of mild hypothermia, which may underlie their
      geroprotective effects.

PMID- 28509495
TI  - [Metabolic syndrome and cognitive impairment in aging patients with
      dyscirculatory encephalopathy].
AB  - The relationship between metabolic syndrome and its individual components, leptin
      levels and the severity of cognitive impairment in patients of different age with
      dyscirculatory encephalopathy (DE) and metabolic syndrome (MS) was studied. There
      were 503 patients aged 45-89 years with DE enrolled into the study, who were
      divided into two groups: patients without MS (n=198) and with MS (n=305). All
      patients were divided into three age subgroups. All patients underwent clinical
      neurological examination, laboratory tests, high resolution B-mode ultrasound
      examination, MRI. Cognitive functions were assessed by Mini Mental State
      Examination (MMSE). In middle age and elderly patients a significant inverse
      relationship between the total score of MMSE and the level of blood pressure,
      blood glucose level was found. A direct significant correlation between blood
      pressure level and a total score of MMSE was revealed in senile patients. The
      duration of hypertension significantly influenced on the severity of cognitive
      impairment in patients of middle and old age. The results obtained indicate a
      definite relationship between the level of leptin in the blood of patients with
      MS and the state of their cognitive functions. The influence of leptin level on
      cognitive function in patients with the metabolic syndrome increases with age.
      Timely and adequate correction of blood pressure, blood glucose and triglycerides
      may have a positive effect on cognitive function in patients with MS.

PMID- 28509496
TI  - [Ways of life quality improvement among elderly and older patients after
      phacoemulsification of cataract in postoperative period].
AB  - The article is devoted to the literature review of modern methods of diagnosis
      and surgical treatment of age-related cataract. The comparative analysis of
      morphologic characteristics of corneal endothelial cell before and after
      phacoemulsification in the age aspect has been given. The results of surgical
      treatment of this disease have been analyzed. The methods of prevention and
      therapy of the postoperative complications have been described. Drug
      administration scheme in the postoperative period is presented. The influence of
      peptides on the cellular immunity indices and stimulation of regenerative
      processes in eye's tissues in different diseases and pathological conditions
      after surgical operation are considered. It has been given the estimation of the
      ratio of visual function and quality of life in the elderly.

PMID- 28509497
TI  - [Metabolic risk factors in patients 60 years and older with arterial
      hypertension, living in extreme conditions of the Far North].
AB  - To evaluate the criteria of metabolic syndrome (MS) in elderly, 505 men aged 60
      99 years, with hypertension, indigenous and non-indigenous ethnic group living in
      the extreme conditions of the Far North were studied. The analysis of
      anthropometric parameters revealed that height, body weight, BMI, waist
      circumference, hip circumference, the ratio of waist to hip size, waist to growth
      were significantly lower in the elderly and senile Yakuts compared with those of
      non-indigenous ethnicity (p<0,001). Ethnic differences were found in SBP and DBP
      levels (p<0,001). The obtained results suggest that in elderly, old age patients
      and centenarians living in the Far North, almost all analyzed parameters of the
      metabolic syndrome were significantly correlated with abdominal obesity
      (p<0,001).

PMID- 28509498
TI  - [Prevalence of stomalgy and its causes in people of different age].
AB  - On the basis of analysis of primary medical records of 9 158 (3 329 males and 5
      829 females) patients of average, elderly and old age of outpatient clinics the
      prevalence of pain and paresthesys of the oral mucosa and tongue was studied.
      Profile of outpatient medical institutions, where people suffering from painful
      phenomena and paresthesys of the oral mucosa pass examination and treatment was
      defined. The causal factors that play a role in the origin and development of
      this disease in patients of older age groups were established.

PMID- 28509499
TI  - [Influence of gerodietetic meat pate on metabolic parameters in the elderly: the
      role of vitamin B12].
AB  - Many studies indicate essential nature of food in maintaining health. An
      important factor is the consumption of a variety of essential elements, in
      particular vitamins. The aim was to determine the relationship of vitamin B12
      levels in serum with metabolic parameters and the possibility of correction using
      gerodietetic meat pate. A total of 23 older people (60-80 years) were surveyed.
      We determined index mass body, waist circumference, biochemical indicators,
      vitamin B12 concentration in serum and food consumption (by frequency method). We
      also measured changes in these parameters under the influence of eating
      gerodietetic meat pate. The older adults often demonstrate deficient in vitamin
      B12 in the blood (about 65 % of the surveyed), which may be contributed both by
      its lack of dietary intake and malabsorption due to pathological changes in the
      digestive system. The content of vitamin B12 in the blood of the elderly has been
      closely linked to metabolic indicators and body mass. Using gerodietetic meat
      pate promoted not only the elimination of vitamin B12 deficiency, but also
      significantly improved the biochemical markers of protein, and especially lipid
      metabolism in the elderly (decreased low-density lipoprotein and high density
      lipoprotein increased).

PMID- 28509500
TI  - [Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old
      female rhesus monkeys].
AB  - The aim of the investigation was comparative study of the influence tetrapeptide
      Pancragen (St. Petersburg Institute of Bioregulation and Gerontology, St.
      Petersburg) on hormonal function of the pancreas compared to the effect of widely
      used hypoglycemic drug - glimepiride. The investigation involved 9 old (20-25
      years) clinically healthy rhesus monkey females (Macaca mulatta). Five of them
      were injected with Pancragen (0,05 mg/animal per day during 10 days,
      intramuscularly) for 10 days; 4 animals received glimepiride (4 mg/animal per day
      during 10 days, per os). Blood samples were taken from all the animals with
      subsequent analysis of glucose, insulin and C peptide levels; the manipulation
      was performed before administration of the drugs, on the background of their
      administration and after their withdrawal in basal conditions, as well as during
      glucose tolerance testing. Pancragen and glimepiride administration induced the
      decrease of blood glucose basal levels in both groups of old monkeys. Pancragen
      also normalized insulin and C peptide levels suggesting its recovering effect on
      the disturbed tolerance to glucose in old animals. At the same time, glimepiride
      administration led to a more expressed and delayed hypoglycemic effect and C
      peptide secretion stimulation without any significant effect on insulin
      secretion. The data suggest that Pancragen is effective and safe for correction
      of age-related imbalance of endocrine pancreatic function, and can be used for
      elderly patient with disturbed glucose tolerance.

PMID- 28509501
TI  - [The quality of life of elderly citizens in Kazakhstan (by the example of
      Astana)].
AB  - The article presents the results of the study of self-assessment of quality of
      life of older Kazakhstan citizens. The differences between the self-assessment of
      quality of life of older people living in institutional care in the hospital and
      outside the hospital are discussed. The results show that elderly people who live
      in institutional care in a hospital, assess the quality of life is better than
      older people living independently.

PMID- 28509502
TI  - [Preventive geriatrics vs anti-aging medicine].
AB  - The article presents the main modern ideas of the new interdisciplinary direction
      at the junction of aesthetic medicine, geriatrics and valeology - preventive
      geriatrics, or the anti-aging medicine. Describes its purpose, namely effective
      individual programs of prevention of the development and progression of chronic
      diseases and age-related conditions; the overview of the diagnostic methods used
      in preventive geriatrics, individualized prevention programs with proven efficacy
      is given. Substantiates the importance of preventive geriatrics (anti-aging
      medicine) as a discipline with its own scientific methodological tools, points of
      application, and presents prospects of scientific study.

PMID- 28509503
TI  - 'Own-Label' Versus Branded Commercial Dental Resin Composite Materials:
      Mechanical And Physical Property Comparisons.
AB  - A majority of dental materials are manufactured by companies who have experience
      in the field. However, a number of "own label" materials have become available,
      principally marketed by distributors and other companies with little or no
      experience in the field. These materials are attractive because of their reduced
      cost, but they may have no research on which clinicians might base their
      potential performance. It is therefore the purpose of this work to compare the
      performance of different batches of a number of "own-label" dental materials with
      a similar number from manufacturers with experience in the field, using a variety
      of laboratory test regimes which include filler determination, degree of
      conversion, flexural strength and flexural modulus, in order to evaluate key
      material properties. The results indicated that own-label dental resin composites
      produced similar results to materials from established companies in terms of
      flexural strength characteristics and degree of conversion. However, a greater
      batch-to-batch variation in several mechanical and physical properties of the own
      label materials was noted.

PMID- 28509504
TI  - Marginal Adaptation, Gap Width, and Fracture Strength of Teeth Restored With
      Different All-Ceramic Vs Metal Ceramic Crown Systems: An in Vitro Study.
AB  - This study evaluated marginal adaptation before and after thermomechanical (TCML)
      loading, gap width and fracture strength of all-ceramic single crowns, as
      compared to porcelain-fused-to-metal (PFM). Thirty extracted premolars were
      prepared with a round shoulder of 1.0 mm depth. Specimens were restored with
      zirconia-ceramic (Group 1), lithium disilicate (Group 2) and metal-ceramic single
      crowns (Group 3). The replica of each sample was observed with a scanning
      electron microscope (SEM) to evaluate the crown-cement (c-c) and tooth-cement
      interface (t-c). After TCML, perfect margins decreased to 91.3% (c-c) and 93.9%
      (t-c) in Group 1, 94.6% (c-c) and 96.0% (t-c) in Group 2 and 73.5% (c-c) and
      53.1% (t-c) in Group 3. The mean fracture strengths were 654.8 +/- 98.1 N for
      Group 1, 551.3 +/- 127 N for Group 2 and 501.43 +/- 110.1 N for Group 3. All
      ceramic systems could substitute for metal-ceramic crowns, but chipping of
      veneering ceramics, especially in zirconia-based crowns, should be investigated.

PMID- 28509505
TI  - Effects of Different Porcelains and Shades on Light Transmission and Resin
      Polymerization.
AB  - This study evaluated the effect of light-curing through two ceramics on the
      degree of conversion-(DC) and Knoop microhardness-(KHN) of resin cements. Three
      shades were used and light-cured directly on a Golden Gate attenuated total
      reflectance FT-IR plate at 30 degrees C. KHN was tested immediately and after 24
      h. Resin shade, type of ceramic, and storage time all had significant effects on
      the DC and KHN values. Within each shade, the choice of ceramic always had a
      significant effect, but the shade of the resin had a greater effect. There was an
      increase in KHN of all cements after 24-h of storage.

PMID- 28509506
TI  - Anti-Inflammatory and Regenerative Effects of Albanian Propolis in Experimental
      Vital Amputations.
AB  - This study evaluated the effects of Albanian propolis on the inflamed pulpal
      tissue after pulpotomy in piglets. In five piglets, two teeth each were infected
      using special pathogenic microbial flora that was prepared in advance in order to
      cause inflammation of the pulp. Pulpotomy was performed in the maxillary and
      mandibular central and lateral incisors. Microbial flora pathogenesis prepared
      from the section of infected teeth, containing Staphylococcus aureus,
      Streptococcus viridans, Enterococcus faecalis, Staphylococcus albus and mixed
      flora were used to cause artificial pulpitis. The first group consisted of
      piglets with the teeth having pulpal inflammation and regeneration without
      medication served as the control group. In the second group, the teeth were
      treated with pure propolis after vital amputation. In the 3rd, 4th and 5th
      groups, the teeth were treated after vital amputation with the compounds of
      ZnO+10%, ZnO+20% propolis in ethanol, and with the paste composed of Ca(OH) +30%
      oily propolis, respectively. In half of the teeth, propolis based pastes were
      applied on the pulp and entries of the cavities were isolated with glass ionomer
      cement while the other half did not receive this treatment and acted as the
      control. The cavity entries were obturated with chemically polymerized resin
      composite. Inflammatory response, dominated by polymorphonuclear cells, was
      observed in the dental pulpal tissue of all the teeth that were not treated with
      propolis-based paste. Radiography and histopathology analyses were performed to
      survey the infected pulp tissue treated with propolis up to 3 months. Data were
      analyzed using Mann-Whitney U test (a=0.05). After vital amputation of the pulp,
      application of Albanian propolis showed significantly higher anti-inflammatory
      and regenerative effect creating dentin barrier after 3 months of treatment
      compared to control group (p?0.05). These results were more expressed in the
      group containing 20% propolis in ethanol+ZnO.

PMID- 28509508
TI  - A Survey on Prevalence, Causes and Prevention of Postcementation
      Hypersensitivity.
AB  - This study evaluated the prevalence and causes of post-cementation sensitivity
      and possible prevention measures according to the experience of dentists through
      an internet survey. A questionnaire was prepared with 25 items based on a survey
      introduced by Rosenstiel and Rashid. An online site was created for the
      participation to the survey. A total of 322 participants responded the
      questionnaire. The results of the questionnaire indicated the amount of tooth
      preparation (42.1%) is the most frequent reason for hypersensitivity followed by
      water-cooling with pressure (11.2%) and provisionals (10.9%). "Very important"
      response for tooth reduction, time before cementation, overheating, luting agent,
      occlusion and provisionals were found to be of statistical significance
      (p?0.001). Comparing respondents' opinions the incidence of post-cementation
      sensitivity appears to be underestimated. Tooth reduction, preparation under high
      volume spray and quality of provisional restorations was considered to have a
      significant impact on the incidence of post-cementation sensitivity according to
      the dentists surveyed across Turkey. Respondents to the questionnaire considered
      the use of antimicrobial, desensitizing, resin bonding, hemostatic agents,
      varnishes, type of liner material, rotary instruments to be less effective for
      prevention of post-cementation sensitivity.

PMID- 28509507
TI  - A Practice-Based Clinical Evaluation of a Bulk Fill Restorative Material.
AB  - OBJECTIVE: To evaluate the handling, by a group of practice-based researchers, of
      a recently introduced bulk fill resin-based composite restorative material,
      Filtek Bulk Fill Restorative (3M ESPE). METHODS: The twelve selected evaluators
      were sent explanatory letters, a pack of the material under investigation to use
      for 8 weeks, and a questionnaire. RESULTS: The evaluators rated the ease of use
      of the bulk fill restorative the same as the previously used posterior composite
      material. The provision of one shade only for evaluation may have compromised the
      score for aesthetic quality. No post-operative sensitivity was reported.
      CONCLUSIONS: The bulk fill material was well received as indicated by the high
      number of evaluators who would both purchase the material and recommend it to
      colleagues. CLINICAL REVELANCE: A recently introduced bulk fill restorative
      material achieved a rating for handling which was similar to the evaluators'
      previously used resin composite, although there were some concerns regarding the
      translucency of the material.

PMID- 28509509
TI  - Fracture of Zirconia Abutment with Metallic Insertion on Anterior Single Titanium
      Implant with Internal Hexagon: Retrieval Analysis of a Failure.
AB  - This case report presents a retrieval analysis of a screw-retained one-piece
      restoration with the veneering ceramic fired directly onto the zirconia abutment
      that fractured during insertion. A patient who experienced root fracture of a
      maxillary left central incisor received a titanium implant on the same day as
      extraction. After delayed implant loading, a two-piece zirconia abutment with
      metallic insertion was customized. Upon installation, a horizontal fracture of
      the crown just above the metallic portion was detected. The retrieval analysis of
      a fractured zirconia abutment showed crack formation and diffusion of glaze
      material that expanded the crack line during firing.

PMID- 28509510
TI  - Editorial: Selling a sugar tax: the sweet smell of success?
AB  - This editorial briefly considers the increasing epidemic of obesity and Type 2
      diabetes, the underlying drivers of junk food and sugary drinks, and the recent
      scientific and campaigning movements culminating in the UK Chancellor's surprise
      announcement of a Sugary Drinks Levy.

PMID- 28509511
TI  - The teaching of Dental Public Health - 50 years on.
AB  - In 1966, James published an article in the British Dental Journal (and reprinted
      here) which made recommendations on the teaching of dental public health. The
      following commentary reviews the ideas put forward by James and how these relate
      to concepts of dental public health in the undergraduate dental curricula of 2016
      .

PMID- 28509512
TI  - The teaching of Dental Public Health and its relation to Children's Dentistry.

PMID- 28509513
TI  - Challenges identified in a pilot outreach dental service for Traveller children
      in Hackney, East London.
AB  - Impetus for action: Inequity of dental health and dental service use for
      Travellers in the UK. National guidance on improving community oral health,
      stresses an imperative to involve and engage with "those whose economic, social
      and environmental circumstances or lifestyle place them at high risk of poor oral
      health or make it difficult for them to access dental services". Solution: Oral
      health promotion and simple treatments were provided on two Traveller sites from
      a mobile dental unit (MDU) over a 5-day period and patients with extensive oral
      disease were referred to a fixed-site clinic for continued care. Outcomes: Most
      children, 60%, reportedly brushed once daily or less, only 40% brushed twice
      daily. Obvious visual caries were evident in 23 out of the 35 children (66%). A
      moderate to high risk of developing future caries was identified in 92% of
      Traveller children based on their existing diet, oral hygiene practices and
      caries experience. Future: Oral care was successfully provided on an MDU, but
      this is an expensive resource and should not be considered a permanent solution.
      Oral health promotion messages delivered in the families' homes or local
      community settings through their established health services, such as health
      visitors or community nurses, may help to reinforce good oral hygiene and diet
      practices and needs robust evaluation.

PMID- 28509514
TI  - Lay public's use of a support group for general dental problems.
AB  - OBJECTIVE: To categorize and tabulate layperson inquiries made to an Internet
      dental health support site to identify oral conditions and associated behaviors
      of concern. METHODS: A retrospective tabulation of wall postings was made from an
      established dental health support website hosted by WebMD over a 2-year period
      (April 2013-April 2015). A mixed method approach of content and thematic analysis
      was used. Content analysis identified content of oral health concerns, while
      thematic analysis using grounded theory identified themes and beliefs concerning
      associated behaviors. RESULTS: The presence of non-descript growths on the tongue
      and swelling and/or discoloration of the lips elicited the most inquires. These
      were often self-diagnosed as oral candidiasis, a STD or a carcinoma, provoking
      high levels of self-concern. Unprotected sexual activity, excessive ingestion of
      soft and hard beverages, smoking and overexposure to the sun were the most
      frequently self-reported behaviors associated with their concerns. Many questions
      focused upon "normal" healing, including the amount of edema and discomfort that
      could occur following oral surgery or other dental procedures. Information
      concerning alternative treatments was often solicited, and many alluded that they
      had not been provided sufficient information to make informed decisions prior to
      dental treatment. CONCLUSIONS: Laypersons have many oral health concerns
      particularly in relationship to the development of undiagnosed pathologies in
      conjunction with a history of volitional behaviors. The dental community should
      monitor these sites to provide advice and links to information about common oral
      health concerns and their possible association with detrimental behaviors.

PMID- 28509515
TI  - Understanding avoidance and non-attendance among adolescents in dental care - an
      integrative review.
AB  - OBJECTIVE: To review articles exploring manifestations of avoidance of or non
      attendance to dental care, to identify background and concomitant factors
      specifically associated with dental avoidance among adolescents. METHODS: PubMed,
      CINAHL and PsychINFO were searched using MeSH terms and keywords covering dental
      avoidance, non-attendance and non-utilization. Searches were limited to peer
      reviewed studies in English, published in 1994-2014. Twenty-one research articles
      were included. Data were extracted, ordered, coded, categorized, and summarized
      according to the integrative review method. RESULTS: The identified factors
      formed three common major themes: Environmental, Individual and Situational
      factors. Only seven studies, all from Sweden or Norway, investigated factors
      associated with dental avoidance. The remaining 14 studies were geographically
      widespread. Regarding avoidance, the main focus was found to be on individual and
      situational factors, while environmental factors were more often investigated for
      the outcome non-attendance. CONCLUSIONS: Although a wide variety of
      environmental, individual and situational factors could be summarized in this
      review, factors specifically associated with dental avoidance in a context of
      free dental care still need to be investigated. The possible impacts of cultural
      background, of tobacco, alcohol or drug use and of psycho-social circumstances
      deserve further research. Clinical implications of today's knowledge may be to
      pay attention to the adolescents' individual background and everyday life
      situation, to offer agreed and individualized treatment, taking fears and
      attitudes into consideration, to avoid painful treatments, and to be alert for
      early signs of avoidance.

PMID- 28509516
TI  - Variations in survival time for amalgam and resin composite restorations: a
      population based cohort analysis.
AB  - OBJECTIVE: To estimate the association between the restorative material used and
      time to further treatment across population cohorts with universal coverage for
      dental treatment. BASIC RESEARCH DESIGN: Cohort study of variation in survival
      time for tooth restorations over time and by restoration material used based on
      an Accelerated Failure Time model. CLINICAL SETTING: Primary dental care clinics.
      PARTICIPANTS : Members of Canada's First Nations and Inuit population covered by
      the Non-Insured Health Benefits program of Health Canada for the period April 1,
      1999 to March 31, 2012. INTERVENTION : Tooth restorations using resin composite
      or amalgam material. MAIN OUTCOME : Survival time of restoration to further
      treatment. RESULTS : Median survival time for resin composite was 51 days longer
      than amalgam, for restorations placed in 1999-2000. This difference was not
      statistically significant (p?0.05). Median survival times were lower for females,
      older subjects. Those visiting the dentist annually, and decreased monotonically
      over time from 11.2 and 11.3 years for resin composite and amalgam restorations
      respectively placed in 1999-2000 to 6.9 and 7.0 years for those placed in 2009
      10. CONCLUSIONS : Resin composite restorations performed no better than amalgams
      over the study period, but cost considerably more. With the combination of the
      overall decrease in survival times for both resin composite and amalgam
      restorations and the increase in use of resin composite, the costs of serving
      Health Canada's Non-Insured Health Benefits population will rise considerably,
      even without any increase in the incidence of caries.

PMID- 28509517
TI  - Impact of providing free preventive dental products without health workers'
      counselling on infants' tooth-brushing and bottle-feeding termination practices:
      a randomised controlled trial.
AB  - OBJECTIVE: To investigate the impact of an integrated oral health promotion
      intervention, within the Syrian national immunisation programme, which provided
      free preventive dental health products, without health workers' counselling, on
      one-year-old infants' tooth-brushing and bottle-feeding termination practices.
      RESEARCH DESIGN: a randomised controlled parallel-group trial. SETTING: A
      maternal and child health centre in Sweida city, Syria. PARTICIPANTS : 92 mothers
      of one-year-old infants, attending an infant vaccination clinic, were allocated
      into three groups: Test, Control One and Control Two. INTERVENTIONS : The Test
      group received an oral health promotion package including an infant oral health
      pamphlet, a baby toothbrush, fluoride toothpaste (1,000 mg/L) and a trainer cup,
      without health workers' counselling. Control One received only the pamphlet,
      whilst Control Two received no intervention. MAIN OUTCOME MEASURES : after one
      month, the presence of old plaque on infants' primary teeth was checked, to
      assess tooth-brushing behaviour. Also, a mothers' self-completed questionnaire
      was administered to assess bottle-feeding use. RESULTS : The response rate was
      100% and the attrition rate was zero. There were differences in tooth-brushing
      and bottle-feeding termination practices between the three groups (P?0.001).
      Infants in the Test group were less likely to have old plaque and more likely to
      stop bottle-feeding than their counterparts in the two control groups. There were
      no differences in the abovementioned outcomes between the two control groups.
      CONCLUSIONS : Providing free preventive dental health products, without health
      worker's counselling, in an integrated oral health promotion intervention, was an
      effective measure to promote infants' tooth-brushing and bottle-feeding
      termination practices. These findings should be supported by long-term follow up
      studies.

PMID- 28509518
TI  - The dental public health implications of cosmetic dentistry: a scoping review of
      the literature.
AB  - INTRODUCTION: The popularity of cosmetic surgery has seen a rapid increase
      recently, with the trend mirrored in dentistry. The Department of Health
      expressed concerns about the potential for biological and psychosocial harm of
      these cosmetic procedures. Furthermore, the dental public health implications
      (DPH) of the growing uptake of cosmetic dental procedures have not been explored.
      OBJECTIVES: Conduct a scoping review to explore the DPH implications of cosmetic
      dentistry and identify gaps for future research. METHODS: A fivestage scoping
      review was conducted of studies identified using the search terms cosmetic AND
      dentistry. Data from the studies meeting the inclusion criteria were extracted,
      collated and summarised into themes. RESULTS : Fifty-seven papers met the
      inclusion criteria (11 cross-sectional studies, 10 literature reviews and 36
      opinion pieces). The DPH implications were summarised into five emergent themes:
      dento-legal and ethical, marketing, psychosocial, biological and workforce. These
      themes revealed patients' increased expectations, expanding commercialisation of
      the profession, psychological risks to vulnerable patients, the iatrogenic
      consequences of invasive cosmetic dental procedures and workforce implications of
      the current trends. CONCLUSIONS : The scoping review found that existing
      literature on cosmetic dentistry is predominately anecdotal - professional
      opinions and discussions. Despite this, our findings demonstrated workforce
      training and governance implications due to increased demand for cosmetic
      dentistry. Further empirical research is needed to understand the DPH
      implications of the increasing demand and uptake of cosmetic dental procedures to
      guide evidence-based policy to safeguard patients and improve the quality of
      dental services.

PMID- 28509519
TI  - Development of life story experience (LSE) scales for migrant dentists in
      Australia: a sequential qualitative-quantitative study.
AB  - INTRODUCTION: The integration of qualitative and quantitative approaches
      introduces new avenues to bridge strengths, and address weaknesses of both
      methods. OBJECTIVE: To develop measure(s) for migrant dentist experiences in
      Australia through a mixed methods approach. METHODS: The sequential qualitative
      quantitative design involved first the harvesting of data items from qualitative
      study, followed by a national survey of migrant dentists in Australia. Statements
      representing unique experiences in migrant dentists' life stories were deployed
      the survey questionnaire, using a five-point Likert scale. Factor analysis was
      used to examine component factors. RESULTS : Eighty-two statements from 51
      participants were harvested from the qualitative analysis. A total of 1,022 of
      1,977 migrant dentists (response rate 54.5%) returned completed questionnaires.
      Factor analysis supported an initial eight-factor solution; further scale
      development and reliability analysis led to five scales with a final list of 38
      life story experience (LSE) items. Three scales were based on home country
      events: health system and general lifestyle concerns (LSE1; 10 items), society
      and culture (LSE4; 4 items) and career development (LSE5; 4 items). Two scales
      included migrant experiences in Australia: appreciation towards Australian way of
      life (LSE2; 13 items) and settlement concerns (LSE3; 7 items). CONCLUSION : The
      five life story experience scales provided necessary conceptual clarity and
      empirical grounding to explore migrant dentist experiences in Australia. Being
      based on original migrant dentist narrations, these scales have the potential to
      offer in-depth insights for policy makers and support future research on dentist
      migration.

PMID- 28509520
TI  - Dental pain and its determinants in an adult population in Tehran, Iran, Urban
      HEART-2.
AB  - OBJECTIVE: To assess the prevalence of dental pain in the past year among adults
      in Tehran-Iran, and its determinants. BASIC RESEARCH DESIGN: Cross-sectional
      population study. PARTICIPANTS: A sample of 20,322 adults (18-64 years old).
      METHODS : A questionnaire survey was conducted across the 22 districts using the
      multi-stage random sampling method. Data were analysed applying the complex
      samples method. Multiple logistic regression analysis was used to adjust the
      effects of other variables on the outcome variable as dental pain in the past
      year. RESULTS : Overall, 19,645 individuals with a mean age of 39.9 (SD=12.5)
      years responded. Dental pain in the past year was reported by about one sixth
      (14%) of subjects and associated with being widowed/divorced (OR 1.45, 95%CI 1.07
      1.97, p=0.016), married (OR 1.24, 95%CI 1.04-1.47, p=0.016), Azari minority (OR
      1.2, 95%CI 1.05-1.37, p=0.009) and having dental visit in the past year (OR 2.6,
      95%CI 2.29-2.95,p?0.001). Older subjects (OR 0.76, 95%CI 0.59-0.97, p= 0.029),
      those with a high economic status (OR 0.84, 95%CI 0.72-0.98, p=0.03), good (OR
      0.75, 95%CI 0.58-0.96, p=0.023) or moderate oral health behaviour (OR 0.79, 95%CI
      0.62-0.99, p=0.042), and good self-perceived oral health (OR 0.52, 95%CI 0.45
      0.61, pp?0.001) were less likely to report dental pain. CONCLUSIONS : Dental pain
      in the past year was associated with being married/widowed, being a minority, and
      visiting a dentist in the past year. Older subjects and those with a high socio
      economic status, good/moderate oral health behaviour, and good self-perceived
      oral health were less likely to report dental pain.

PMID- 28509521
TI  - Dermatofibrosarcoma protuberans: when the age makes the difference.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans is a malignant tumor that affects
      exclusively the skin. It is a low-grade malignant tumor of subcutaneous tissues,
      characterized by a local recurrence but it seldom metastasizes. This study aimed
      to evaluate the impact of different clinical parameters on disease free survival
      and overall survival of dermatofibrosarcoma protuberans patients. METHODS: A
      retrospective study of data including seventeen cases of dermatofibrosarcoma
      protuberans (eleven male, six female) retrieved from the files of the Dermatology
      Clinics of La Sapienza University, Rome. We evaluated three clinical parameters
      (age, sex and anatomic site of the primary tumor) using the Kaplan-Meier product
      and the Log-Rank Test. RESULTS: The results highlighted that patients with an age
      <=49 years showed a median disease free survival of 36 months, while patients
      with an age >=50 years of 4 months (P<0.0003). In addition, performing Rank
      correlation, only the variable age (P<0.0001) reached the statistical
      significance. Regarding overall survival, performing Rank-correlation only the
      variable age reached the statistical significance (P=0.02). CONCLUSIONS: Our data
      suggests that age has a statistically significant role on disease free survival
      and overall survival of dermatofibrosarcoma protuberans patients.

PMID- 28509522
TI  - Construction of a three-dimensional in-vitro skin model on polycaprolactone
      fibers.
AB  - BACKGROUND: The aim of this study was to observe the morphological
      characteristics and the biological properties of human epidermal cells when
      cultured at an air-liquid interface in polycaprolactone (PCL) fibers as a three
      dimensional scaffold for tissue engineering. METHODS: In this study, the
      melanocytes and keratinocytes were obtained from human scalp skin, seeded onto a
      PCL film, and cocultured for 2 weeks to construct a three-dimensional (3D) skin
      model. The cells were then characterized by hematoxylin and eosin staining, by
      immunohistochemical staining with antibodies to cytokeratin 15 (CK15), Ki-67,
      CD34, CD200 and HMB45 and by transmission electron microscopy. RESULTS:
      Keratinocytes and melanocytes grew well in the co-culture system. Hematoxylin and
      eosin staining revealed that the cells adhered to the PCL fiber scaffold well,
      the keratinocyte layer became a multilayered concentric structure and the surface
      became distinctly keratinized at the air-liquid interface. Immunohistochemical
      analyses exhibited a scattered distribution of cells expressing CK15, CD34,
      CD200, Ki-67 and/or HMB45. Transmission electron microscopy revealed that the
      keratinocytes contained a number of keratin fibrils and membrane-coated granules.
      CONCLUSIONS: The PCL scaffold has excellent adhesiveness and biocompatibility
      with human epidermal cells, and is suitable for constructing 3D skin models for
      tissue engineering in the future.

PMID- 28509523
TI  - Skin diseases and tattoos: a five-year experience.
AB  - BACKGROUND: Decorative tattooing as a body art form underwent an exponential
      increase during the last two decades, particularly among teenagers and young
      adults. Consequently, the number of reported adverse reactions after tattooing
      has increased. The most frequent reported skin reactions to tattoo include
      infectious (bacterial, viral, fungal) or inflammatory (allergic contact
      dermatitis and granulomatous reaction) diseases. Moreover, tattoos can also
      induce the development of typical skin lesions of pre-existing dermatoses, a
      phenomenon known as isomorphism reactive or Koebner phenomenon, which commonly
      occurs in patients with psoriasis, vitiligo, or lichen planus. METHODS: A
      retrospective study analyzing records data of patients attending the Department
      of Dermatology, University of Naples "Federico II" during 2011-2015 was
      performed. All cases of tattoo-related or closely-located dermatitis were
      selected. RESULTS: We observed 19 patients (mean age: 26.4 years old) showing
      cutaneous conditions related to the practice of tattooing. Allergic contact
      dermatitis was reported as the most common cutaneous disease linked to tattooing
      (31.6%), followed by granulomatous reactions (26.3%). These data are consistent
      with those already reported in the literature. CONCLUSIONS: Our results highlight
      the need to develop detailed regulations regarding tattoos practice, used
      materials, as well as execution procedures in order to limit the outbreak of
      tattoo-related skin diseases.

PMID- 28509524
TI  - Eradication of basal cell carcinoma of the head and neck using the surgical
      excision with a new stained margin technique: a preliminary study.
AB  - BACKGROUND: Basal cell carcinomas (BCCs) are common cutaneous neoplasms that
      mainly affect fair-skinned subjects, in sun-exposed areas of the body. The
      treatment of choice of BCCs is represented by surgical excision and different
      techniques are available, in order to allow the complete eradication of the tumor
      with the best cosmetic results. In this paper, we describe the surgical excision
      with stained margin technique (SMET) and we report its efficacy for the treatment
      of BCCs of the head and neck region. METHODS: We retrospectively studied 177 BCCs
      of the head and neck region treated by SMET: a surgical technique in which each
      specimen is cut vertically like a bread-loaf in multiple sections of 1 mm of
      thickness, after marking peripheral margins. RESULTS: We observed an overall
      recurrence rate of 4.5% after SMET (mean follow-up: 26 months), with higher rate
      in aggressive subtypes (P=0.04). BCCs located in high-risk sites and those
      previously undergone to other non-radical therapies required two or more
      procedures (P=0.008 and P=0.002, respectively), while no correlation was observed
      between the number of SMET procedures and recurrence rate. CONCLUSIONS: In our
      experience, since low recurrence rate was obtained by SMET, we suggest that it
      may be taken into consideration as surgical option for BCCs of the head and neck
      region.

PMID- 28509526
TI  - Paraoxonases and psoriasis: negative imbalance of anti--oxidant endogenous
      mechanisms.
AB  - BACKGROUNG: Numerous reports have shown that psoriasis patients are more exposed
      to lipoprotein peroxidation and to a decrease in the activity of paraoxonase
      (PON)1, an anti-oxidant and anti-inflammatory enzyme. Thus, it has been suggested
      that malfunction of the anti-oxidant system and an increased production of
      reactive oxygen species drive immune inflammatory events, that result in
      progressive skin cell damage in patients with psoriasis. The PON protein family,
      including PON1, PON2 and PON3, is one of the most important endogenous defense
      mechanisms against oxidative stress. In the present study, we investigated PON
      gene expression in psoriasis and in cutaneous oxidative stress. METHODS: The
      study population included 10 patients affected by moderate-to-severe plaque
      psoriasis and 15 healthy donors who have undergone to plastic surgery, were used
      as control. Skin punch biopsies of lesional and non lesional psoriatic skin were
      performed for analysis of PON2 and PON3 gene expression. In addition, oxidation
      assays in ex vivo full-thickness healthy skin organ cultures were performed.
      RESULTS: No significant differences were observed between PON2 and PON3 gene
      expression in psoriatic lesional and non lesional skin compared with healthy
      controls. H2O2 treatment induced a significant decrease of PON2 and PON3
      expression in ex vivo full-thickness healthy skin organ cultures; conversely the
      pre-treatment of samples with the anti-oxidant reagent N-acetyl-L-cysteine (NAC)
      induced a significant increase. Interestingly, no significant alterations were
      reported for PON2 and PON3 expression in ex vivo full-thickness healthy skin
      organ cultures stimulated with IL-17. CONCLUSIONS: Taken together our findings
      have revealed that a strong pro-oxidative activity is not effectively countered
      by anti-oxidant endogenous mechanisms both in psoriatic skin and in ex vivo
      experimental model.

PMID- 28509527
TI  - Robotically assisted minimally invasive mitral valve surgery.

PMID- 28509528
TI  - Synthesis of Water-Soluble Ag2S Quantum Dots with Fluorescence in the Second Near
      Infrared Window for Turn-On Detection of Zn(II) and Cd(II).
AB  - The second near-infrared window emission (1.0-1.7 MUm, NIR-II) has received
      extensive attention with the advantages of negligible tissue scattering, reduced
      autofluorescence, and less background noise. Here a novel analysis platform based
      on quantum dots (QDs) for highly selective detection of Zn2+ and Cd2+ with an
      enhanced NIR-II fluorescence is reported for the first time. We have developed a
      facile two-step route to synthesize the water-soluble Ag2S QDs, constituting of a
      green hydrothermal process and followed surface ligands exchange. Surface
      passivation was proposed to be the mechanism for the enhanced fluorescence. The
      added Zn2+ or Cd2+ could react with the surface thioglycollic acid to form Zn
      thiol or Cd-thiol complex passivation shell, which restored surface defects and
      suppressed nonradiative recombination pathway. The detection platform exhibited a
      linear relationship between the ion concentrations and enhanced fluorescence and
      had a detection limit as low as 760 nM for Zn2+ and 546 nM for Cd2+ at pH = 7.4.
      Furthermore, the as-synthesized Ag2S QDs showed good robustness in real sample
      matrix and were demonstrated to be able to detect exogenous Zn(II) in cells.
      These properties suggest potential applications of detection of Zn2+ in biology
      and Cd2+ in environment via the NIR-II fluorescent Ag2S QDs.

PMID- 28509529
TI  - Orientation Control of Interfacial Magnetism at La0.67Sr0.33MnO3/SrTiO3
      Interfaces.
AB  - Understanding the magnetism at the interface between a ferromagnet and an
      insulator is essential because the commonly posited magnetic "dead" layer close
      to an interface can be problematic in magnetic tunnel junctions. Previously,
      degradation of the magnetic interface was attributed to charge discontinuity
      across the interface. Here, the interfacial magnetism was investigated using
      three identically prepared La0.67Sr0.33MnO3 (LSMO) thin films grown on different
      oriented SrTiO3 (STO) substrates by polarized neutron reflectometry. In all cases
      the magnetization at the LSMO/STO interface is larger than the film bulk. We show
      that the interfacial magnetization is largest across the LSMO/STO interfaces with
      (001) and (111) orientations, which have the largest net charge discontinuities
      across the interfaces. In contrast, the magnetization of LSMO/STO across the
      (110) interface, the orientation with no net charge discontinuity, is the
      smallest of the three orientations. We show that a magnetically degraded
      interface is not intrinsic to LSMO/STO heterostructures. The approach to use
      different crystallographic orientations provides a means to investigate the
      influence of charge discontinuity on the interfacial magnetization.

PMID- 28509531
TI  - Hierarchical Porous Structured SiO2/SnO2 Nanofibrous Membrane with Superb
      Flexibility for Molecular Filtration.
AB  - The separation and purification of chemical molecules from organic media under
      harsh chemical environments are of vital importance in the fields of water
      treatment, biomedical engineering, and organic recycling. Herein, we report the
      preparation of a flexible SiO2/SnO2 nanofibrous membrane (SiO2/SnO2 NFM) with
      high surface area and hierarchical porous structure by selecting poly(vinyl
      butyral) as pore-forming agent and embedding crystalline phase into amorphous
      matrix without using surfactant as sacrificial template. Benefiting from the
      uniform micropore size on the fibers and negatively charged properties, the
      membranes exhibit a precise selectivity toward molecules based on electrostatic
      interaction and size exclusion, which could separate organic molecule mixtures
      with the same electrostatic charges and different molecular sizes with a high
      efficiency of more than 97%. Furthermore, the highly tortuous open-porous
      structures and high porosity give rise to a high permeate flux of 288 000 L m-2 h
      1. In addition, the membrane also displays excellent stability and can be reused
      for ten consecutive filtration-regeneration cycles. The integration of high
      filtration efficiency, large permeate flux, good reutilization, and easy to
      industrialization provides the SiO2/SnO2 NFM for potential applications in
      practical molecular purification and separation science.

PMID- 28509530
TI  - Role of Modulators in Controlling the Colloidal Stability and Polydispersity of
      the UiO-66 Metal-Organic Framework.
AB  - Nanoscale UiO-66 Zr6(OH)4O4(C8O4H4)6 has been synthesized with a series of
      carboxylic acid modulators, R-COOH (where R = H, CH3, CF3, and CHCl2). The phase
      purity and size of each MOF was confirmed by powder X-ray diffraction, BET
      surface area analysis, and scanning transmission electron microscopy (STEM). Size
      control of UiO-66 crystals from 20 nm to over 1 MUm was achieved, and confirmed
      by STEM. The colloidal stability of each MOF was evaluated by dynamic light
      scattering and was found to be highly dependent on the modulator conditions
      utilized in the synthesis, with both lower pKa and higher acid concentration
      resulting in more stable structures. Furthermore, STEM was carried out on both
      colloidally stable samples and those that exhibited a large degree of
      aggregation, which allowed for visualization of the different degrees of
      dispersion of the samples. The use of modulators at higher concentrations and
      with lower pKas leads to the formation of more defects, as a consequence of
      terephthalic acid ligands being replaced by modulator molecules, thereby
      enhancing the colloidal stability of the UiO-66 nanoparticles. These findings
      could have a significant impact on nanoscale MOF material syntheses and
      applications, especially in the areas of catalysis and drug delivery.

PMID- 28509532
TI  - Nanodiamonds Mediate Oral Delivery of Proteins for Stem Cell Activation and
      Intestinal Remodeling in Drosophila.
AB  - Introduction of exogenous biomacromolecules into living systems is of great
      interest in genome editing, cancer immunotherapy, and stem cell reprogramming.
      Whereas current strategies generally depend on nucleic acids transfection, direct
      delivery of functional proteins that provides enhanced specificity, increased
      safety, and fast and temporal regulation is highly desirable. Nevertheless,
      intracellular delivery of intact and bioactive proteins, especially in vivo,
      remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based
      protein delivery system in cultured cells and in Drosophila that showed high
      adsorption, high efficiency, and effective cytosolic release of fully functional
      proteins. Through live-cell imaging, we observed a novel phenomenon wherein a
      substantial amount of internalized NDs-protein complex rejected fusion with the
      early endosome, thereby evading protein degradation in the lysosome. More
      significantly, we demonstrated that dietary NDs-RNase induced apoptosis in
      enterocytes, stimulating regenerative divisions in intestinal stem cells and
      increasing the number of stem cells and precursor cells in Drosophila intestine.
      As stem cells are poorly accessible by exogenous agents in vivo, NDs-mediated
      oral delivery of proteins provides a new approach to modulate the stem cell
      microenvironment for intestinal remodeling, which has important implications for
      colorectal cancer therapy and regenerative medicine.

PMID- 28509533
TI  - Low-Cost Label-Free Biosensing Bimetallic Cellulose Strip with SILAR-Synthesized
      Silver Core-Gold Shell Nanoparticle Structures.
AB  - We introduce a label-free biosensing cellulose strip sensor with surface-enhanced
      Raman spectroscopy (SERS)-encoded bimetallic core@shell nanoparticles. Bimetallic
      nanoparticles consisting of a synthesis of core Ag nanoparticles (AgNP) and a
      synthesis of shell gold nanoparticles (AuNPs) were fabricated on a cellulose
      substrate by two-stage successive ionic layer absorption and reaction (SILAR)
      techniques. The bimetallic nanoparticle-enhanced localized surface plasmon
      resonance (LSPR) effects were theoretically verified by computational
      calculations with finite element models of optimized bimetallic nanoparticles
      interacting with an incident laser source. Well-dispersed raspberry-like
      bimetallic nanoparticles with highly polycrystalline structure were confirmed
      through X-ray and electron analyses despite ionic reaction synthesis. The
      stability against silver oxidation and high sensitivity with superior SERS
      enhancement factor (EF) of the low-cost SERS-encoded cellulose strip, which
      achieved 3.98 * 108 SERS-EF, 6.1%-RSD reproducibility, and <10%-degraded
      sustainability, implicated the possibility of practical applications in high
      analytical screening methods, such as single-molecule detection. The remarkable
      sensitivity and selectivity of this bimetallic biosensing strip in determining
      aquatic toxicities for prohibited drugs, such as aniline, sodium azide, and
      malachite green, as well as monitoring the breast cancer progression for urine,
      confirmed its potential as a low-cost label-free point-of-care test chip for the
      early diagnosis of human diseases.

PMID- 28509534
TI  - Analysis of Three Epoetin Alpha Products by LC and LC-MS Indicates Differences in
      Glycosylation Critical Quality Attributes, Including Sialic Acid Content.
AB  - Erythropoietin (EPO) is one of the main therapeutics used to treat anemic
      patients, greatly improving their quality of life. In this study, biosimilars
      Binocrit and a development product, called here CIGB-EPO, were compared to the
      originator product, Eprex. All three are epoetin alpha products, reputed to have
      similar glycosylation profiles. The quality, safety, and efficacy of this
      biotherapeutic depend on the following glycosylation critical quality attributes
      (GCQAs): sialylation, N-glycolyl-neuraminic acid (Neu5Gc) content, branching, N
      acetyl-lactosamine (LacNAc) extensions, and O-acetylation pattern. Reverse-phase
      ultra-high-pressure liquid chromatography (RP-UHPLC) analysis of acid-released,
      1,2-diamino-4,5-methylenedioxybenzene (DMB) labeled sialic acid derivatives and
      hydrophilic interaction liquid chromatography (HILIC) in combination with mass
      spectrometry (HILIC-UHPLC-MS) of procainamide (PROC) labeled N-glycans were the
      analytical tools used. An automated method for enzymatic release and PROC
      labeling was applied for the first time to the erythropoiesis stimulating agent
      (ESA) products, which facilitated novel, in-depth characterization, and allowed
      identification of precise structural features including the location of O-acetyl
      groups on sialic acid (SA) moieties. Samples were digested by a sialate-O
      acetylesterase (NanS) to confirm the presence of O-acetyl groups. It was found
      that Eprex contained the greatest relative abundance of O-acetylated derivatives,
      Binocrit expressed the least Neu5Gc, and CIGB-EPO showed the greatest variety of
      high-mannose-phosphate structures. The sialylation and LacNAc extension patterns
      of the three ESAs were similar, with a maximum of four N-acetyl-neuraminic acid
      (Neu5Ac) moieties detected per glycan. Such differences in SA derivatization,
      particularly O-acetylation, could have consequences for the quality and safety of
      a biotherapeutic, as well as its efficacy.

PMID- 28509535
TI  - Molybdenum-Tungsten Mixed Oxide Deposited into Titanium Dioxide Nanotube Arrays
      for Ultrahigh Rate Supercapacitors.
AB  - A novel method involving the fabrication of Mo-W mixed oxide (MoxW1-xO3) is
      proposed to modify the modest reaction kinetics and poor cycling stability of
      MoO3 material. By a simple coelectrodeposition method, a series of MoxW1-xO3
      oxides is deposited on a TiO2 nanotube array substrate. Because of the
      differences between Mo6+ and W6+ in nature, there is significant distortion
      existing in the mixed oxides, leading to their decreased crystallite size and
      enlarged lattice space, which facilitates ion diffusion in the solid. As results,
      the mixed oxides show much better balance between specific capacitance and
      cycling stability than the bare MoO3 or WO3 sample, which suffers from either
      poor cycling stability or low electrochemical activity. Impressively, the optimal
      Mo-W mixed oxide exhibits a high specific capacitance of 517.4 F g-1 at 1 A g-1,
      and, moreover, it retains 89.3% of the capacitance even at a high current density
      of 10 A g-1, demonstrating ultrahigh rate capability. These findings reveal the
      potential of the Mo-W mixed oxide for constructing advanced ultrahigh power
      supercapacitors.

PMID- 28509536
TI  - Long-Lived Polypyridyl Based Mononuclear Ruthenium Complexes: Synthesis,
      Structure, and Azo Dye Decomposition.
AB  - Two mononuclear ruthenium complexes [(bpy)2RuIIL1/L2](ClO4)2 ([1]2+/[2]2+) (bpy
      2,2' bipyridine, L1 = 2,3-di(pyridin-2-yl)pyrazino[2,3-f][1,10]phenanthroline)
      and L2 = 2,3-di(thiophen-2-yl)pyrazino[2,3-f][1,10]phenanthroline have been
      synthesized. The complexes have been characterized using various analytical
      techniques. The complex [1]2+ has further been characterized by its single
      crystal X-ray structure suggesting ruthenium is coordinating through the N donors
      of phenanthroline end. Theoretical investigation suggests that the HOMOs of both
      complexes are composed of pyridine and pyrazine unit of ligands L1 and L2 whereas
      the LUMOs are formed by the contribution of bipyridine units. The low energy
      bands at ~480 nm of the complexes can be assigned as MLCT with partial
      contribution from ligand transitions, whereas the rest are ligand centered. The
      complexes have shown RuII/RuIII oxidation couples at E1/2 at 1.26 (70 mV) V and
      1.28 (62 mV) V for [1]2+ and [2]2+ vs Ag/AgCl, respectively, suggesting no
      significant role of distal thiophene or pyridine units of the ligands. The
      complexes are emissive and display solvent dependent emission properties. Both
      complexes have shown highest emission quantum yield and lifetime in DMSO (phi =
      0.05 and tauavg = 460 ns and lambdamaxem at 620 nm for [1]2+; phi = 0.043 and
      tauavg = 425 ns and lambdamaxem at 635 nm for [2]2+). Further, the long
      luminescent lifetime of these complexes has been utilized to generate reactive
      oxygen species for efficient azo dye decomposition.

PMID- 28509537
TI  - [(18-C-6)K][(N=C)CuI-SiMe2Ph], a Potassium Silylcyanocuprate as a Catalyst Model
      for Silylation Reactions with Silylboranes: Syntheses, Structures, and Catalytic
      Properties.
AB  - CuI-catalyzed silylation reactions involving silylboranes (in particular, pinB
      SiMe2Ph (1)) as silyl sources have recently gained considerable attention. One of
      the most efficient and versatile and yet simplest catalyst systems consists of
      CuCN/NaOMe; however, nothing is known about the catalytically relevant species.
      Using an NHC-based model catalyst, copper silyl complexes of the type [(NHC)Cu
      SiMe2Ph] have been established to be crucial species in these catalytic
      processes. The well-defined and spectroscopically and structurally characterized
      complex [(18-C-6)K][NC-Cu-OtBu] (2), as a model for the catalytic system,
      CuCN/NaOMe, shows comparable catalytic activity toward established, exemplary
      substrates (aldehydes, imines, alpha,beta-unsaturated carbonyls) and in extension
      allows the efficient silylation of ketones. In addition, a number of
      peculiarities of the catalytic reaction are readily rationalized on the basis of
      the mechanistic insight already established using [(NHC)Cu-SiMe2Ph] as a model
      catalyst. Analogously to the NHC model system, the reaction of 2 with the
      silylborane 1 furnishes the silylcyanocuprate [(18-C-6)K][NC-Cu-SiMe2Ph] (3) as a
      potential crucial intermediate in these silylation reactions also suggesting
      mechanistic similarities between (NHC)Cu- and CuCN/NaOMe-based catalyst systems.
      Moreover, 3 and [(NHC)Cu-SiMe2Ph] complexes also share structurally distinctive
      features. In the solid state 3 either exists as a linear, two-coordinated copper
      complex or, depending on the conditions of crystallization, forms binuclear MU
      silyl bridged dimers exhibiting very short Cu...Cu distances. Both structural
      motifs are also known for [(NHC)Cu-SiR3] complexes. These findings give an
      initial insight into the versatile structural chemistry of certain
      silylcyanocuprates; in particular, the finding of dinuclear silylcuprates gives
      rise to the question whether these dimeric species are of mechanistic relevance
      for the catalytic processes. However, all peculiarities of the investigated
      catalytic reaction can readily be rationalized on the basis of the mechanistic
      details established using (NHC)Cu model complexes.

PMID- 28509538
TI  - Bis(thiosemicarbazone) Complexes of Cobalt(III). Synthesis, Characterization, and
      Anticancer Potential.
AB  - Nine bis(thiosemicarbazone) (BTSC) cobalt(III) complexes of the general formula
      [Co(BTSC)(L)2]NO3 were synthesized, where BTSC = diacetyl bis(thiosemicarbazone)
      (ATS), pyruvaldehyde bis(thiosemicarbazone) (PTS), or glyoxal
      bis(thiosemicarbazone) (GTS) and L = ammonia, imidazole (Im), or benzylamine
      (BnA). These compounds were characterized by multinuclear NMR spectroscopy, mass
      spectrometry, cyclic voltammetry, and X-ray crystallography. Their stability in
      phosphate-buffered saline was investigated and found to be highly dependent on
      the nature of the axial ligand, L. These studies revealed that complex stability
      is primarily dictated by the axial ligand following the sequence NH3 > Im > BnA.
      The cellular uptake and cytotoxicity in cancer cells were also determined. Both
      the cellular uptake and cytotoxicity were significantly affected by the nature of
      the equatorial BTSC. Complexes of ATS were taken up much more effectively than
      those of PTS and GTS. The cytotoxicity of the complexes was correlated to that of
      the free ligand. Cell uptake and cytotoxicity were also determined under hypoxic
      conditions. Only minor differences in the hypoxia activity and uptake were
      observed. Treatment of the cancer cells with the copper-depleting agent
      tetrathiomolybdate decreased the cytotoxic potency of the complexes, indicating
      that they may operate via a copper-dependent mechanism. These results provide a
      structure-activity relationship for this class of compounds, which may be applied
      for the rational design of new cobalt(III) anticancer agents.

PMID- 28509539
TI  - Tunable Luminescent Lanthanide Supramolecular Assembly Based on Photoreaction of
      Anthracene.
AB  - Lanthanide luminescence materials generally show great superiority in light
      emitting materials, gaining increasingly exploration in the design of advanced
      functional materials. Herein, we prepared a supramolecular assembly via the
      coordination of a host molecule (1) and dilanthanide metal. Compound 1 possesses
      a 9,10-diphenylanthracene (ant) core with photosensitivity and terminal
      terpyridine (tpy), containing two-arm dibenzo-24-crown-8. The assembly could
      exhibit excellent lanthanide luminescence after undergoing a photoreaction from
      anthracene unit in 1. Significantly, the luminescence of the assembly could be
      reversibly switched on and off through a regulable photoreaction upon light
      irradiation or heating. The multiple functional behavior combined with the ease
      of assembly reveals that this photo/thermo-controlled lanthanide luminescence
      supramolecular polymer design method offers a convenient pathway for future
      engineering of multi-stimuli-responsive materials.

PMID- 28509540
TI  - Characterization of the High-Spin Co(II) Intermediate Species of the O2-Evolving
      Co4O4 Cubic Molecules.
AB  - An artificial oxygen-evolving complex (OEC) contains a tetranuclear CoIII4O4
      cubic cluster ligated with acetate and pyridine molecules, a light-activated
      Ru(bpy)32+ moiety (bpy = 2,2'-bipyridine), and the sacrificial electron acceptor
      S2O82- side. A recent EPR investigation of this system showed the formation of
      the high-spin Co(II) ion under visible-illumination conditions. It has been
      supported that this center originates from the cluster and is involved in the
      oxygen-evolving process. The present report is focused on the further
      characterization of the high-spin d7 configuration of the Co(II) species. The
      measurement of the EPR spectrum at a wider magnetic field range in comparison to
      that reported recently shows the presence of an additional signal that
      contributes to the spectrum of the Co(II) center. The theoretical simulation of
      this spectrum reveals that an isotropic g value and considerably small zero-field
      splitting parameters describe the high-spin Co(II) ion in a unique way, which
      supports a tetrahedral crystal field symmetry. On the basis of the spin
      Hamiltonian parameters, the looping transitions that lead to the experimental EPR
      signals are determined. Additionally, a possible role of the symmetry of the
      Co(II) species and a proposed model that explains its formation during the O2
      evolving process of the Co4O4 cubic molecules are discussed.

PMID- 28509541
TI  - Synthesis, Characterization, and Variable-Temperature NMR Studies of Silver(I)
      Complexes for Selective Nitrene Transfer.
AB  - An array of silver complexes supported by nitrogen-donor ligands catalyze the
      transformation of C?C and C-H bonds to valuable C-N bonds via nitrene transfer.
      The ability to achieve high chemoselectivity and site selectivity in an amination
      event requires an understanding of both the solid- and solution-state behavior of
      these catalysts. X-ray structural characterizations were helpful in determining
      ligand features that promote the formation of monomeric versus dimeric complexes.
      Variable-temperature 1H and DOSY NMR experiments were especially useful for
      understanding how the ligand identity influences the nuclearity, coordination
      number, and fluxional behavior of silver(I) complexes in solution. These insights
      are valuable for developing improved ligand designs.

PMID- 28509542
TI  - Trimethylsulfonium Lead Triiodide: An Air-Stable Hybrid Halide Perovskite.
AB  - We report on the synthesis, characterization, and optoelectronic properties of
      the novel trimethylsulfonium lead triiodide perovskite, (CH3)3SPbI3. At room
      temperature, the air-stable compound adopts a hexagonal crystal structure with a
      1D network of face-sharing [PbI6] octahedra along the c axis. UV-vis reflectance
      spectroscopy on a pressed pellet revealed a band gap of 3.1 eV, in agreement with
      first-principles calculations, which show a small separation between direct and
      indirect band gaps. Electrical resistivity measurements on single crystals
      indicated that the compound behaves as a semiconductor. According to multi
      temperature single-crystal X-ray diffraction, synchrotron powder X-ray
      diffraction, Raman spectroscopy, and differential scanning calorimetry, two fully
      reversible structural phase transitions occur at -5 and ca. -100  degrees C with
      reduction of the unit cell symmetry to monoclinic as temperature decreases. The
      role of the trimethylsulfonium cation regarding the chemical stability and
      optoelectronic properties of the new compound is discussed in comparison with
      APbI3 (A = Cs, methylammonium, and formamidinium cation), which are most commonly
      used in perovskite solar cells.

PMID- 28509543
TI  - Exploring the Gas-Phase Activation and Reactivity of a Ruthenium Transfer
      Hydrogenation Catalyst by Experiment and Theory in Concert.
AB  - This study elucidates structures, activation barriers, and the gas-phase
      reactivity of cationic ruthenium transfer hydrogenation catalysts of the
      structural type [(eta6-cym)RuX(pympyr)]+. In these complexes, the central
      ruthenium(+II) ion is coordinated to an eta6-bound p-cymene (eta6-cym), a
      bidentate 2-R-4-(2-pyridinyl)pyrimidine ligand (pympyr) with R = NH2 or N(CH3)2,
      and an anion X = I-, Br-, Cl-, or CF3SO3-. We present infrared multiple-photon
      dissociation (IR-MPD) spectra of precursors (before HCl loss) and of activated
      complexes (after HCl loss), which elucidates C-H activation as the key step in
      the activation mechanism. A resonant two-color IR-MPD scheme serves to record
      several otherwise "dark" bands and enhances the validity of spectral assignments.
      We show that collision-induced dissociation (CID)-derived activation energies of
      the [(eta6-cym)RuX(pympyr)]+ (R = N(CH3)2) complexes depend crucially on the
      anion X. The obtained activation energies for the HX loss correlate well with
      quantum chemical activation barriers and are in line with the HSAB concept. We
      further elucidate the reaction of the activated complexes with D2 under single
      collision conditions. Quantum mechanical simulations substantiate that the
      resulting species represent analogues for hydrido intermediates formed after
      abstraction of H+ and H- from isopropanol, as postulated for the catalytic cycle
      of transfer hydrogenation by us before.

PMID- 28509544
TI  - Search for Electron Delocalization from [Fe(CN)6]3- to the Dication of Viologen
      in (DNP)3[Fe(CN)6]2.10H2O.
AB  - K3Fe(CN)6 reacts with the viologen 1,1'-bis(2,4-dinitrophenyl)-4,4'-bipyridinium
      dication, (DNP)2+, to form a supramolecular complex, (DNP)3[Fe(CN)6]2.10H2O (1).
      The crystal structure of 1 reveals that there are two [Fe(CN)6]3- anions within
      an organic framework of three (DNP)2+ cations with the shortest Fe(III)...Fe(III)
      distances of ca. 9.8 A, distances that minimize extensive long-range magnetic
      exchange coupling interactions between the [Fe(CN)6]3- anions, and, thus, 1 is
      paramagnetic above ca. 17 K and exhibits weak ferromagnetic coupling between 17
      and 3 K and antiferromagnetic coupling between 3 and 1.8 K. The long
      Fe(III)...Fe(III) distances permit slow spin-spin and slow spin-lattice
      paramagnetic relaxation, relative to the iron-57 Larmor precession frequency, as
      is evidenced by the Mossbauer spectra measured between 3 and 60 K; between 85 and
      295 K, rapid paramagnetic relaxation is observed. Both the slow spin-spin and
      slow spin-lattice relaxation are mediated by the organic, pi-conjugated viologen
      cations. The Fe-C distances, the Mossbauer isomer shifts, the temperature
      dependence of the magnetic susceptibility, and the 3 K magnetization results all
      indicate the presence of low-spin Fe(III) ions in the [Fe(CN)6]3- anions in 1.
      There is no unequivocal indication of the presence of any formal electron
      delocalization or transfer from the [Fe(CN)6]3- anion to the (DNP)2+ cations in
      the results obtained from X-ray crystallography, magnetic measurements, and
      Mossbauer spectra. Because of enhancement of the spin-orbit coupling by the heavy
      atom or -ion effect, the Fe(III) ions in the [Fe(CN)6]3- anions interact with the
      (DNP)2+ cations, causing them to fluoresce with increasing intensity upon cooling
      from 90 to 25 K when excited at 300 nm. The resulting luminescence of the
      viologen (DNP)2+ cation induced by the [Fe(CN)6]3- anions indicates the presence
      of significant mixing of the molecular orbitals derived from the [Fe(CN)6]3-
      anions and the molecular orbitals associated with the (DNP)2+ cations to yield
      bonding supramolecular orbitals in 1, a mixing that is also observed between 50
      and 3 K in the temperature dependence of the isomer shift of 1.

PMID- 28509545
TI  - Highly Coordinated Iron and Cobalt Nitrides Synthesized at High Pressures and
      High Temperatures.
AB  - Highly coordinated iron and cobalt nitrides were successfully synthesized via
      direct chemical reaction between a transition metal and molecular nitrogen at
      pressures above approximately 30 GPa using a laser-heated diamond anvil cell. The
      synthesized novel transition metal nitrides were found to crystallize into the
      NiAs-type or marcasite-type structure. NiAs-type FeN could be quenched at ambient
      pressure, although it was gradually converted to the ZnS-type structure after the
      pressure was released. On the other hand, CoN was recovered with ZnS-type
      structure through a phase transition from NiAs-type structure at approximately a
      few gigapascals during decompression. Marcasite-type CoN2 was also synthesized at
      pressures above approximately 30 GPa. High-pressure in situ X-ray diffraction
      measurement showed that the zero-pressure bulk modulus of marcasite-type CoN2 is
      216(18) GPa, which is comparable to that of RhN2. This indicates that the
      interatomic distance of the N-N dimer in marcasite-type CoN2 is short because of
      weak orbital interaction between cobalt and nitrogen atoms, as in RhN2.
      Surprisingly, a first-principles electronic band calculation suggests that the
      NiAs-type FeN and CoN and marcasite-type CoN2 exhibit metallic characteristics
      with magnetic moments of 3.4, 0.6, and 1.2 MUB, respectively. The ferromagnetic
      NiAs-type structure originates from the anisotropic arrangement of transition
      atoms stacked along the c axis.

PMID- 28509547
TI  - Photoinduced Charge Shifts and Electron Transfer in Viologen-Tetraphenylborate
      Complexes: Push-Pull Character of the Exciplex.
AB  - Viologen-tetraarylborate ion-pair complexes were prepared and investigated by
      steady-state and time-resolved spectroscopic techniques such as fluorescence and
      femtosecond transient absorption. The results highlight a charge transfer
      transition that leads to changes in the viologen structure in the excited singlet
      state. Femtosecond transient absorption reveals the formation of excited-state
      absorption and stimulated emission bands assigned to the planar (kobs < 1012 s-1)
      and twisted (kobs ~ 1010 s-1) structures between two pyridinium groups in the
      viologen ion. An efficient photoinduced electron transfer from the
      tetraphenylborate anionic moiety to the viologen dication was observed less than
      1 MUs after excitation. This is a consequence of the push-pull character of the
      electron donor twisted viologen structure, which helps formation of the borate
      triplet state. The borate triplet state is deactivated further via a second
      electron transfer process, generating viologen cation radical (V*+).

PMID- 28509546
TI  - Growth of Nitrosococcus-Related Ammonia Oxidizing Bacteria Coincides with
      Extremely Low pH Values in Wastewater with High Ammonia Content.
AB  - Ammonia oxidation decreases the pH in wastewaters where alkalinity is limited
      relative to total ammonia. The activity of ammonia oxidizing bacteria (AOB),
      however, typically decreases with pH and often ceases completely in slightly
      acidic wastewaters. Nevertheless, nitrification at low pH has been reported in
      reactors treating human urine, but it has been unclear which organisms are
      involved. In this study, we followed the population dynamics of ammonia oxidizing
      organisms and reactor performance in synthetic fully hydrolyzed urine as the pH
      decreased over time in response to a decrease in the loading rate. Populations of
      the beta-proteobacterial Nitrosomonas europaea lineage were abundant at the
      initial pH close to 6, but the growth of a possibly novel Nitrosococcus-related
      AOB genus decreased the pH to the new level of 2.2, challenging the perception
      that nitrification is inhibited entirely at low pH values, or governed
      exclusively by beta-proteobacterial AOB or archaea. With the pH shift, nitrite
      oxidizing bacteria were not further detected, but nitrous acid (HNO2) was still
      removed through chemical decomposition to nitric oxide (NO) and nitrate. The
      growth of acid-tolerant gamma-proteobacterial AOB should be prevented, by keeping
      the pH above 5.4, which is a typical pH limit for the N. europaea lineage.
      Otherwise, the microbial community responsible for high-rate nitrification can be
      lost, and strong emissions of hazardous volatile nitrogen compounds such as NO
      are likely.

PMID- 28509548
TI  - U(IV) Aqueous Speciation from the Monomer to UO2 Nanoparticles: Two Levels of
      Control from Zwitterionic Glycine Ligands.
AB  - The fate of U(IV)O2 in the environment in a colloidal form and its dissolution
      and growth in controlled environments is influenced by organic ligation and redox
      processes, where both affect solubility, speciation, and transport. Here we
      investigate U(IV) aqueous speciation from pH 0 to 3 with the glycine (Gly)
      ligand, the smallest amino acid. We document evolution of the monomeric to the
      hexameric form from pH 0 to 3 via UV-vis spectroscopy and small-angle X-ray
      scattering (SAXS). Crystals of the hexamer [U6O4(OH)4(H2O)6(HGly)12].12Cl
      .12(H2O) (U6) were isolated at pH 2.15. The structure of U6 is a hexanuclear
      oxo/hydroxo cluster U6O4(OH)4 decorated by 12 glycine ligands and 6 water
      molecules. The effect of pH and temperature on U6 conversion to UO2
      nanoparticles, or simply reversible aggregation, is detailed by transmission
      electron microscopy imaging, in addition to SAXS and UV-spectroscopy. Because of
      the zwitterion behavior of glycine, pH and temperature control over U(IV)
      speciation is complex. Unexpectedly, stability of the polynuclear cluster
      actually increases with increased pH. Speciation is sensitive to not only metal
      oxo hydrolysis but also ligand lability and hydrophobic ligand-ligand
      interactions.

PMID- 28509550
TI  - Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal
      Exocytosis.
AB  - As a prerequisite to mammalian fertilization, the sperm acrosomal vesicle fuses
      with the plasma membrane and the acrosome contents are exocytosed. Induction
      occurs through engagement of the sperm receptors by multiple sugar residues.
      Multivalent polymers displaying mannose, fucose, or GlcNAc are effective
      synthetic inducers of mouse sperm acrosomal exocytosis (AE). Each carbohydrate is
      proposed to have a distinct binding site on the sperm cell surface. To determine
      the role of the scaffold structure in the efficiency of AE induction, different
      polymer backbones were employed to display the different activating sugar
      residues. These glycopolymers were prepared by ruthenium-catalyzed ring-opening
      metathesis of 5-substituted norbornene or cyclooctene. The conformations of the
      glycopolymers were characterized by small-angle X-ray scattering. Polynorbornene
      displaying mannose, fucose, or GlcNAc forms flexible cylinders in aqueous
      solution. However, polycyclooctenes displaying any of these same sugars are much
      more flexible and form random coils. The flexible polycyclooctenes displaying
      fucose or GlcNAc were less effective inducers of AE than their norbornene
      counterparts. In contrast, polycyclooctene displaying mannose was the most
      effective AE inducer and had a more collapsed spherelike structure. Our results
      suggest that the AE efficacy of fucose, GlcNAc, and mannose polymers relies on a
      relatively rigid polymer that can stabilize receptor signaling complexes.

PMID- 28509549
TI  - Heterogeneous-Backbone Foldamer Mimics of Zinc Finger Tertiary Structure.
AB  - A variety of oligomeric backbones with compositions deviating from
      biomacromolecules can fold in defined ways. Termed "foldamers," these agents have
      diverse potential applications. A number of protein-inspired secondary structures
      (e.g., helices, sheets) have been produced from unnatural backbones, yet examples
      of tertiary folds combining several secondary structural elements in a single
      entity are rare. One promising strategy to address this challenge is the
      systematic backbone alteration of natural protein sequences, through which a
      subset of the native side chains is displayed on an unnatural building block to
      generate a heterogeneous backbone. A drawback to this approach is that
      substitution at more than one or two sites often comes at a significant energetic
      cost to fold stability. Here we report heterogeneous-backbone foldamers that
      mimic the zinc finger domain, a ubiquitous and biologically important metal
      binding tertiary motif, and do so with a folded stability that is superior to the
      natural protein on which their design is based. A combination of UV-vis
      spectroscopy, isothermal titration calorimetry, and multidimensional NMR reveals
      that suitably designed oligomers with >20% modified backbones can form native
      like tertiary folds with metal-binding environments identical to the prototype
      sequence (the third finger of specificity factor 1) and enhanced thermodynamic
      stability. These results expand the scope of heterogeneous-backbone foldamer
      design to a new tertiary structure class and show that judiciously applied
      backbone modification can be accompanied by improvement to fold stability.

PMID- 28509551
TI  - Significance of [2Fe-2S] Cluster N1a for Electron Transfer and Assembly of
      Escherichia coli Respiratory Complex I.
AB  - NADH:ubiquinone oxidoreductase, respiratory complex I, couples electron transfer
      from NADH to ubiquinone with proton translocation across the membrane. NADH
      reduces a noncovalently bound FMN, and the electrons are transported further to
      the quinone reduction site by a 95 A long chain of seven iron-sulfur (Fe-S)
      clusters. Binuclear Fe-S cluster N1a is not part of this long chain but is
      located within electron transfer distance on the opposite site of FMN. The
      relevance of N1a to the mechanism of complex I is not known. To elucidate its
      role, we individually substituted the cysteine residues coordinating N1a of
      Escherichia coli complex I by alanine and serine residues. The mutations led to a
      significant loss of the NADH oxidase activity of the mutant membranes, while the
      amount of the complex was only slightly diminished. N1a could not be detected by
      electron paramagnetic resonance spectroscopy, and unexpectedly, the content of
      binuclear cluster N1b located on a neighboring subunit was significantly
      decreased. Because of the lack of N1a and the partial loss of N1b, the variants
      did not survive detergent extraction from the mutant membranes. Only the C97AE
      variant retained N1a and was purified by chromatographic steps. The preparation
      showed a slightly diminished NADH/ferricyanide oxidoreductase activity, while the
      NADH:decyl-ubiquinone oxidoreductase activity was not affected. N1a of this
      preparation showed unusual spectroscopic properties indicating a different
      ligation. We discuss whether N1a is involved in the physiological electron
      transfer reaction.

PMID- 28509552
TI  - Amino Acid Conjugated Anthraquinones from the Marine-Derived Fungus Penicillium
      sp. SCSIO sof101.
AB  - Emodacidamides A-H (1-8), natural products featuring anthraquinone-amino acid
      conjugates, have been isolated from a marine-derived fungus, Penicillium sp.
      SCSIO sof101, together with known anthraquinones 9 and 10. The planar structures
      of 1-8 were elucidated using a combination of NMR spectroscopy and mass
      spectrometry. The absolute configurations of the amino acid residues were
      confirmed using Marfey's method and chiral-phase HPLC analyses. Additionally,
      isolates were evaluated for possible immunomodulatory and cytotoxic activities.
      Emodacidamides A (1), C (3), D (4), and E (5) inhibited interleukin-2 secretion
      from Jurkat cells with IC50 values of 4.1, 5.1, 12, and 5.4 MUM, respectively.

PMID- 28509553
TI  - Uncovering the Thermo-Kinetic Origins of Phase Ordering in Mixed-Valence Antimony
      Tetroxide by First-Principles Modeling.
AB  - Phase ordering in the mixed-valence oxide Sb2O4 has been examined by density
      functional theory (DFT) calculations. We find that the ground-state total
      energies of the two phases (alpha and beta) are almost degenerate and are highly
      sensitive to the choice of the approximation to the exchange correlation (xc)
      functional used in our calculations. Interestingly, with the inclusion of the
      zero-point energy corrections, the alpha phase is predicted to be the ground
      state polymorph for most xc functionals used. We also illustrate the pronounced
      stereochemical activity of Sb in these polymorphs of Sb2O4, setting an exception
      to the Keve and Skapski rule. Here, we find that the actual bonding in the alpha
      phase is more asymmetric, while the anomalous stability of the beta phase could
      be rationalized from kinetic considerations. We find a non-negligible activation
      barrier for this alpha-beta phase transition, and the presence of a saddle point
      (beta phase) supports the separation of Sb(III) over a continuous phase
      transition, as observed in experiments.

PMID- 28509554
TI  - "Self-Shaping" of Multicomponent Drops.
AB  - In our recent study we showed that single-component emulsion drops, stabilized by
      proper surfactants, can spontaneously break symmetry and transform into various
      polygonal shapes during cooling [ Denkov Nature 2015 , 528 , 392 - 395 ]. This
      process involves the formation of a plastic rotator phase of self-assembled oil
      molecules beneath the drop surface. The plastic phase spontaneously forms a frame
      of plastic rods at the oil drop perimeter which supports the polygonal shapes.
      However, most of the common substances used in industry appear as mixtures of
      molecules rather than pure substances. Here we present a systematic study of the
      ability of multicomponent emulsion drops to deform upon cooling. The observed
      trends can be summarized as follows: (1) The general drop-shape evolution for
      multicomponent drops during cooling is the same as with single-component drops;
      however, some additional shapes are observed. (2) Preservation of the particle
      shape upon freezing is possible for alkane mixtures with chain length difference
      Deltan <= 4; for greater Deltan, phase separation within the droplet is observed.
      (3) Multicomponent particles prepared from alkanes with Deltan <= 4 plastify upon
      cooling due to the formation of a bulk rotator phase within the particles. (4) If
      a compound, which cannot induce self-shaping when pure, is mixed with a certain
      amount of a compound which induces self-shaping, then drops prepared from this
      mixture can also self-shape upon cooling. (5) Self-emulsification phenomena are
      also observed for multicomponent drops. In addition to the three recently
      reported mechanisms of self-emulsification [ Tcholakova Nat. Commun. 2017 , ( 8
      ), 15012 ], a new (fourth) mechanism is observed upon freezing for alkane
      mixtures with Deltan > 4. It involves disintegration of the particles due to a
      phase separation of alkanes upon freezing.

PMID- 28509556
TI  - Structure-Based Selective Adsorption of Graphene on a Gel Surface: Toward
      Improving the Quality of Graphene Nanosheets.
AB  - Top-down graphene production via exfoliation from graphite produces a mass of
      graphene with structural variation in terms of the number of layers, sheet size,
      edge type, and defect density. All of these characteristics affect its electronic
      structure. To develop useful applications of graphene, structural separation of
      graphene is necessary. In this study, we investigate the adsorption behavior of
      different types of graphene fragments using a multicolumn gel chromatography
      system with a view to developing an efficient method for separating high-quality
      graphene. The graphene was dispersed in an aqueous sodium dodecyl sulfate (SDS)
      surfactant solution and flown through allyl-dextran-based gel columns connected
      in series. In the chromatographic operation, we observed that the small-sized or
      oxidized graphene fragments tended to bind to the gel and the relatively large
      sized graphene with a low oxygen content eluted from the gel column. In this
      system, the adsorbed SDS molecules on the graphitic surface prevented graphitic
      materials from binding to the gel and the oxygen functional groups on the
      graphene oxide or at the abundant edge of small-sized graphene hindered SDS
      adsorption. We hypothesize that the reduced SDS adsorption density results in the
      preferential adsorption of small-sized or oxidized graphene fragments on the gel.
      This type of chromatographic separation is a cost-effective and scalable method
      for sorting nanomaterials. The structural separation of graphene based on the
      adsorption priority found in this study will improve the quality of graphene
      nanosheets on an industrial scale.

PMID- 28509555
TI  - Differential Phosphoproteomic Analysis of Recombinant Chinese Hamster Ovary Cells
      Following Temperature Shift.
AB  - Phosphorylation is one of the most important post-translational modifications,
      playing a crucial role in regulating many cellular processes, including
      transcription, cytoskeletal rearrangement, cell proliferation, differentiation,
      apoptosis, and signal transduction. However, to date, little work has been
      carried out on the phosphoproteome in CHO cells. In this study we have carried
      out a large scale differential phosphoproteomic analysis of recombinant CHO cells
      following a reduction of culture temperature (temperature shift). The reduction
      of culture temperature during the exponential phase of growth is commonly
      employed by the biopharmaceutical industry to increase product yield; however,
      the molecular mechanisms of temperature shift in CHO cells remain poorly
      understood. We have identified 700 differentially expressed phosphopeptides using
      quantitative label-free LC-MS/MS phosphoproteomic analysis in conjunction with
      IMAC and TiO2 phosphopeptide enrichment strategies, following a reduction in
      temperature from 37 to 31  degrees C. Functional assessment of the
      phosphoproteomic data using gene ontology analysis showed a significant
      enrichment of biological processes related to growth (e.g., cell cycle, cell
      division), ribosomal biogenesis, and cytoskeleton organization, and molecular
      functions related to RNA binding, transcription factor activity, and protein
      serine/threonine kinase activity. Differential phosphorylation of two proteins,
      ATF2 and NDRG1, was confirmed by Western blotting. This data suggests the
      importance of including the post-translational layer of regulation, such as
      phosphorylation, in CHO "omics" studies. This study also has the potential to
      identify phosphoprotein targets that could be modified using cell line
      engineering approaches to improve the efficiency of recombinant protein
      production.

PMID- 28509557
TI  - Determination of Permeability Coefficients of Polymersomal Membranes for
      Hydrophilic Molecules.
AB  - Polymer vesicles, so-called polymersomes, can be applied as carrier-systems and
      universal reaction compartments, due to the possibility to encapsulate guest
      molecules. Compared to common lipid vesicles, polymersomes show an increased
      stability and decreased membrane permeability. Control of the mass transport
      across the membrane is necessary for any application, requiring the precise
      knowledge of the permeability. So far, data on permeability coefficients of
      polymersomal membranes are scarce because commonly applied release assays are
      confronted with the challenge of high detection limits and alternative methods
      developed so far are either restricted to the use of a certain permeating
      molecule or rely on the use of nuclear magnetic resonance measurements. In
      contrast, an influx assay that is broadly applicable to hydrophilic molecules and
      does not involve specialized equipment was developed in this work, which is based
      on the passive diffusion of compounds into initially empty vesicles. The method
      is valid for hydrophilic molecules that show no membrane retention and, thus, do
      not accumulate within the membrane. Using this method, the permeability of
      polymersomes made of poly(2-methyloxazoline)15-poly(dimethylsiloxane)68-poly(2
      methyloxazoline)15 for seven model compounds was investigated under varying
      conditions. Permeability coefficients as low as 1.9 * 10-14 cm s-1 could be
      measured.

PMID- 28509559
TI  - Evaporation-Driven Deposition of ITO Thin Films from Aqueous Solutions with Low
      Speed Dip-Coating Technique.
AB  - We suggest a novel wet coating process for preparing indium tin oxide (ITO) films
      from simple solutions containing only metal salts and water via evaporation
      driven film deposition during low-speed dip coating. Homogeneous ITO precursor
      films were deposited on silica glass substrates from the aqueous solutions
      containing In(NO3)3.3H2O and SnCl4.5H2O by dip coating at substrate withdrawal
      speeds of 0.20-0.50 cm min-1 and then crystallized by the heat treatment at 500
      800  degrees C for 10-60 min under N2 gas flow of 0.5 L min-1. The ITO films
      heated at 600  degrees C for 30 min had a high optical transparency in the
      visible range and a good electrical conductivity. Multiple-coating ITO films
      obtained with five-times dip coating exhibited the lowest sheet (rhoS) and volume
      (rhoV) resistivities of 188 Omega sq-1 and 4.23 * 10-3 Omega cm, respectively.

PMID- 28509558
TI  - Chiral Structures from Achiral Micellar Lyotropic Liquid Crystals under Capillary
      Confinement.
AB  - Recently, the emergence of spontaneous reflection-symmetry-broken configurations
      in achiral chromonic liquid crystals confined in cylindrical capillaries with
      homeotropic anchoring at the cylinder walls was reported, namely, the so-called
      twisted-escaped radial (TER) and twisted planar polar (TPP) configurations. This
      new example of spontaneous reflection symmetry breaking in liquid crystals was
      attributed to the twist elastic modulus, which is known to be unusually small in
      comparison to the splay and bend moduli in the case of chromonic liquid crystals.
      We now report the experimental observation of reflection symmetry breaking in
      cylindrical capillaries in the case of a classical, achiral, and nonchromonic
      lyotropic liquid crystal forming a nematic phase of disklike micelles orienting
      homeotropically at the capillary walls. We observed the same chiral TER
      configuration, as well as a nonplanar twisted polar (TP) configuration. The TP
      configuration is characterized by two half-unit so-called twist disclinations,
      where the director twist around the line defects drives the formation of a double
      helix of the disclinations along the axis of the capillary. Additionally, there
      is a transverse twist between the two disclination lines with the same handedness
      as the axial twist. Similarities with and differences from the case of chromonic
      liquid crystals are discussed; in particular, we examine the conditions under
      which spontaneous reflection symmetry breaking occurs in the nonchromonic system.
      It seems that the chiral TER configuration can be stabilized by the presence of
      point defects.

PMID- 28509560
TI  - Multiscale Model for Electrokinetic Transport in Networks of Pores, Part II:
      Computational Algorithms and Applications.
AB  - The first part of this two-article series presented a robust mathematical model
      for the fast and accurate prediction of electrokinetic phenomena in porous
      networks with complex topologies. In the second part of this series, we first
      present a numerical algorithm that can efficiently solve the model equations. We
      then demonstrate that the resulting framework is capable of capturing a wide
      range of transport phenomena in microstructures by considering a hierarchy of
      canonical problems with increasing complexity. The developed framework is
      validated against direct numerical simulations of deionization shocks in
      micropore-membrane junctions and concentration polarization in micro- and
      nanochannel systems. We demonstrate that for thin pores subject to concentration
      gradients our model consistently captures correct induced osmotic pressure, which
      is a macroscopic phenomena originally derived from thermodynamic principles but
      here is naturally predicted through microscopic electrostatic interactions.
      Moreover, we show that the developed model captures current rectification
      phenomena in a conical nanopore subject to an axial external electric field.
      Finally, we provide discussions on examples involving stationary and moving
      deionization shocks in micropore nanopore T-junctions as well as induced-flow
      loops when pores of varying sizes are connected in parallel.

PMID- 28509561
TI  - Lattice and Valence Electronic Structures of Crystalline Octahedral Molybdenum
      Halide Clusters-Based Compounds, Cs2[Mo6X14] (X = Cl, Br, I), Studied by Density
      Functional Theory Calculations.
AB  - The electronic and crystal structures of Cs2[Mo6X14] (X = Cl, Br, I) cluster
      based compounds were investigated by density functional theory (DFT) simulations
      and experimental methods such as powder X-ray diffraction, ultraviolet-visible
      spectroscopy, and X-ray photoemission spectroscopy (XPS). The experimentally
      determined lattice parameters were in good agreement with theoretically optimized
      ones, indicating the usefulness of DFT calculations for the structural
      investigation of these clusters. The calculated band gaps of these compounds
      reproduced those experimentally determined by UV-vis reflectance within an error
      of a few tenths of an eV. Core-level XPS and effective charge analyses indicated
      bonding states of the halogens changed according to their sites. The XPS valence
      spectra were fairly well reproduced by simulations based on the projected
      electron density of states weighted with cross sections of Al Kalpha, suggesting
      that DFT calculations can predict the electronic properties of metal-cluster
      based crystals with good accuracy.

PMID- 28509562
TI  - Thiolate Spin Population of Type I Copper in Azurin Derived from 33S Hyperfine
      Coupling.
AB  - The electron transfer mediating properties of type I copper proteins stem from
      the intricate ligand coordination sphere of the Cu ion in their active site.
      These redox properties are in part due to unusual cysteine thiol coordination,
      which forms a highly covalent copper-sulfur (Cu-S) bond. The structure and
      electronic properties of type I copper have been the subject of many experimental
      and theoretical studies. The measurement of spin delocalization of the Cu(II)
      unpaired electron to neighboring ligands provides an elegant experimental way to
      probe the fine details of the electronic structure of type I copper. To date, the
      crucial parameter of electron delocalization to the sulfur atom of the cysteine
      ligand has not been directly determined experimentally. We have prepared 33S
      enriched azurin and carried out W-band (95 GHz) electron paramagnetic resonance
      (EPR) and electron-electron double resonance detected NMR (EDNMR) measurements
      and, for the first time, recorded the 33S nuclear frequencies, from which the
      hyperfine coupling and the spin population on the sulfur of the thiolate ligand
      were derived. The overlapping 33S and 14N EDNMR signals were resolved using a
      recently introduced two-dimensional correlation technique, 2D-EDNMR. The 33S
      hyperfine tensor was determined by simulations of the EDNMR spectra using 33S
      hyperfine and quadrupolar tensors predicted by QM/MM DFT calculations as starting
      points for a manual spectral fit procedure. To reach a reasonable agreement with
      the experimental spectra, the 33S hyperfine principal value, Az, and one of the
      corresponding Euler angles had to be modified. The final values obtained gave an
      experimentally determined sulfur spin population of 29.8 +/- 0.7%, significantly
      improving the wide range of 29-62% reported in the literature. Our direct,
      experimentally derived value now provides an important constraint for further
      theoretical work aimed at unravelling the unique electronic properties of this
      site.

PMID- 28509563
TI  - The Adjunctive Soft-Tissue Diode Laser in Orthodontics.
AB  - Lasers are a relatively new addition to the orthodontist's armamentarium. This
      article reviews the fundamental basic science of available soft-tissue lasers,
      with an emphasis on diode lasers, and discusses various adjunct applications of
      the diode laser for soft-tissue orthodontic procedures. Diode lasers function by
      cutting with an initiated hot tip and produce minimal to no interaction with
      healthy dental hard tissue, making them suitable for soft-tissue procedures. The
      contact cutting mode provides enhanced bloodless site visibility and facility to
      perform delicate soft tissue procedures, which is important in areas with
      difficult access. Such adjunctive uses include laser gingivectomy to improve oral
      hygiene or bracket positioning, esthetic laser gingival recontouring, and laser
      exposure of superficially impacted teeth. Selected cases treated with a 940-nm
      indium-gallium-arsenide-phosphide (InGaAsP) diode laser will be presented.

PMID- 28509565
TI  - A qualitative meta-summary using Sandelowski and Barroso's method for integrating
      qualitative research to explore barriers and facilitators to self-care in heart
      failure patients.
AB  - BACKGROUND: Individual qualitative studies provide varied reasons for why heart
      failure patients do not engage in self-care, yet articles that aggregated primary
      studies on the subject have methodological weaknesses that justified the
      execution of a qualitative meta-summary. AIM: The aim of this study is to
      integrate the findings of qualitative studies pertaining to barriers and
      facilitators to self-care using meta-summary techniques. METHODS: Qualitative
      meta-summary techniques by Sandelowski and Barroso were used to combine the
      findings of qualitative studies. Meta-summary techniques include: (1) extraction
      of relevant statements of findings from each report; (2) reduction of these
      statements into abstracted findings and (3) calculation of effect sizes.
      Databases were searched systematically for qualitative studies published between
      January 2010 and July 2015. Out of 2264 papers identified, 31 reports based on
      the accounts of 814 patients were included in the meta-summary. RESULTS: A total
      of 37 statements of findings provided a comprehensive inventory of findings
      across all reports. Out of these statements of findings, 21 were classified as
      barriers, 13 as facilitators and three were classed as both barriers and
      facilitators. The main themes relating to barriers and facilitators to self-care
      were: beliefs, benefits of self-care, comorbidities, financial constraints,
      symptom recognition, ethnic background, inconsistent self-care, insufficient
      information, positive and negative emotions, organizational context, past
      experiences, physical environment, self-initiative, self-care adverse effects,
      social context and personal preferences. CONCLUSION: Based on the meta-findings
      identified in this study, future intervention development could address these
      barriers and facilitators in order to further enhance self-care abilities in
      heart failure patients.

PMID- 28509564
TI  - Maternal Time Use and Nurturing: Analysis of the Association Between
      Breastfeeding Practice and Time Spent Interacting with Baby.
AB  - BACKGROUND: Breastfeeding supports child development through complex mechanisms
      that are not well understood. Numerous studies have compared how well
      breastfeeding and nonbreastfeeding mothers interact with their child, but few
      examine how much interaction occurs. SUBJECTS AND METHODS: Our study of weekly
      time use among 156 mothers of infants aged 3-9 months investigated whether
      lactating mothers spend more time providing emotional support or cognitive
      stimulation of their infants than nonbreastfeeding mothers, and whether the
      amount of such interactive time is associated with breastfeeding intensity.
      Mothers were recruited via mother's and baby groups, infant health clinics, and
      childcare services, and used an electronic device to record their 24-hour time
      use for 7 days. Sociodemographic and feeding status data were collected by
      questionnaire. Statistical analysis using linear mixed modeling and residual
      maximum likelihood analysis compared maternal time use for those giving "some
      breastfeeding" and those "not breastfeeding." Analysis was also conducted for
      more detailed feeding subgroups. RESULTS: Breastfeeding and nonbreastfeeding
      mothers had broadly similar socioeconomic and demographic characteristics.
      Breastfeeding was found to be associated with more mother-child interaction time,
      a difference only partially explained by weekly maternal employment hours or
      other interactive care activities such as play or reading. CONCLUSION: This study
      presents data suggesting that lactating mothers spent significantly more hours
      weekly on milk feeding and on carrying, holding, or soothing their infant than
      nonlactating mothers; and on providing childcare. Understanding the mechanisms by
      which child mental health and development benefits from breastfeeding may have
      important implications for policies and intervention strategies, and could be
      usefully informed by suitably designed time use studies.

PMID- 28509566
TI  - Respiratory motion during 90Yttrium PET contributes to underestimation of tumor
      dose and overestimation of normal liver tissue dose.
AB  - Background Yttrium-90 dosimetry after radioembolization is reliant on accurate
      quantitative imaging of the microsphere deposition. Previous studies have focused
      on the correction of geometrical resolution effects. Purpose To uncover
      additional effects of respiratory motion. Material and Methods Mathematical
      models describing spherical tumors were formed and two blurring effects, limited
      geometrical resolution and respiratory motion, were simulated. The virtual images
      were used as basis for dose volume histogram estimations by convolving the
      radioactivity representations with a dose point kernel. Results For respiratory
      motion only, the largest errors were found for the smallest tumors and/or tumors
      with heterogeneous distribution of yttrium-90 microspheres. The deviations in max
      dose and dose to 25% and 50% of the tumor volume were estimated at 20-40%, 10
      30%, and 0-30%, respectively. Additional blurring from geometrical resolution
      increased the errors to 55-75%, 50-60%, and 25-60%, respectively. Conclusion
      Respiratory motion contributes to underestimation of tumor dose and
      overestimation of normal tissue dose.

PMID- 28509567
TI  - Early evaluation of radiation-induced parotid damage with diffusion kurtosis
      imaging: a preliminary study.
AB  - Background Radiation-induced parotid gland damage is a common complication of
      radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC), which always
      causes xerostomia, dysphagia, dental caries, and even sleep disorders. Early
      evaluation of radiation-induced parotid damage is required to facilitate early
      interventions. Purpose To early-evaluate radiation-induced parotid damage using
      diffusion kurtosis imaging (DKI) in patients with NPC undergoing RT. Material and
      Methods Thirty-two patients with NPC underwent DKI for parotid glands pre-RT (two
      weeks before RT), mid-RT (five weeks after RT began), and post-RT (four weeks
      after RT). Parotid volume, apparent diffusion coefficient (ADC), corrected
      diffusion coefficient (D), excess diffusion kurtosis coefficient (K) values, mean
      radiation dose, and xerostomia degrees were recorded and analyzed. Results During
      RT, parotid ADC (change rates = 41.3 +/- 25.2% at mid-RT, 70.8 +/- 34.3% at post
      RT) and D (change rates = 41.9 +/- 25.2% at mid-RT, 63.2 +/- 30.2% at post-RT)
      increased, while parotid volume (atrophy rates = 31.5 +/- 7.9% at mid-RT, 30.6 +/
      10.3% at post-RT) and K (change rates = -17.8 +/- 11.0% at mid-RT, -29.8 +/-
      9.0% at post-RT) decreased significantly (all P < 0.001). At post-RT, the change
      rate of parotid D values was significantly positively correlated with the mean
      radiation dose ( r = 0.455, P < 0.001). Parotid ADC, D, and K values showed
      excellent intra- and inter-observer agreement (intraclass correlation coefficient
      = 0.946-0.985). Conclusion Radiation-induced parotid damage in patients with NPC
      undergoing RT could be effectively evaluated by DKI in the early stage.

PMID- 28509568
TI  - Low body weight and clinical outcomes in acute coronary syndrome patients:
      results of the ACHILLES Registry.
AB  - BACKGROUND: Being overweight increases the risk of cardiovascular diseases and
      mortality. However, among high-body-weight patients with established acute
      coronary syndrome (ACS) this evidence is not clear. In this scenario, a low body
      weight (LBW) has been proposed to confer higher prognostic risk and higher
      bleeding risk with new P2Y12 inhibitors. AIMS: We aimed to examine differences in
      mortality, catheterizations/revascularizations, antiplatelet therapy and
      ischemic/bleeding adverse events between ACS patients with LBW. METHODS: This is
      a multicenter registry involving 1576 consecutive ACS patients (ST-elevation
      myocardial infarction (STEMI), non-STEMI, or unstable angina) from three tertiary
      institutions. Patients were divided into two groups: LBW (weight < 60 kg, n =
      176) and non-LBW (weight ? 60 kg, n = 1400). During 12 months follow-up, we
      recorded management (catheterizations/revascularizations), antiplatelet therapy,
      major adverse cardiovascular events (MACEs), bleeding events (BARC
      classification), and mortality. RESULTS: Catheterizations (86.4% vs. 93.4%; p =
      0.001) and revascularizations (64.8% vs. 76.1%; p = 0.001) were significantly
      lower in the LBW group. At discharge, prescription of new P2Y12 inhibitors was
      also lower in LBW patients (24.4% vs. 37.8%; p = 0.001). After 12-month follow
      up, the incidence of MACE (HR 1.61 (95% CI 1.03-2.50]; p = 0.038) and mortality
      (HR 2.18 (95% CI 1.33-3.58); p = 0.002) was higher in LBW patients compared with
      non-LBW. In contrast, there were no significant differences for bleeding events.
      CONCLUSIONS: LBW in ACS patients was associated with higher incidence of MACE and
      mortality. In this group of patients less catheterizations and coronary
      revascularizations were performed. Despite there being no differences in bleeding
      rates, new P2Y12 inhibitors were less prescribed in LBW patients.

PMID- 28509569
TI  - HIV-1 CRF07_BC with a Seven Amino Acid Deletion in the gag p6 Region Dominates in
      HIV-1-Infected Men Who Have Sex with Men in China.
AB  - We examined sequence variation in the HIV-1 gag p6 region from 27 individuals
      infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from
      the Los Alamos National Laboratory database were also analyzed. A unique deletion
      of seven amino acid (aa) (p6Delta7) (aa 30-36, PIDKELY, in the HXB2 genome) was
      observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the
      CRF07_BC sequences contained the p6Delta7 mutation. The prevalence of the
      p6Delta7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected
      intravenous drug users and men who have sex with men (MSM), respectively. Our
      results demonstrate that the p6Delta7 mutation dominates in MSM infected by HIV-1
      CRF07_BC in China and suggests that this deletion could serve as a useful marker
      for monitoring HIV-1 evolution and epidemic. In future studies, it will be of
      interest to determine whether such genotypic variation influences viral
      replication capacity and disease progression.

PMID- 28509570
TI  - Learners' perspectives on the provision of condoms in South African public
      schools.
AB  - A stubborn health challenge for learners in South African public schools concerns
      sexual and reproductive health and rights (SRHR). In 2015, the Department of
      Basic Education (DBE) proposed the provision of condoms and SRHR-services to
      learners in schools. This study aimed to contribute to the finalisation and
      implementation of DBE's policy by exploring learners' perspectives on the
      provision of condoms and SRHR-services in schools. Sixteen focus group
      discussions were conducted with learners (n = 116) from 33 public schools, to
      assess their attitudes, social influences, and needs and desires regarding condom
      provision and SRHR-services in schools. The majority of learners did not support
      condom provision in schools as they feared that it may increase sexual activity.
      Contrarily, they supported the provision of other SRHR-services as clinics fail
      to offer youth-friendly services. Learners' sexual behaviour and access to SRHR
      services are strongly determined by their social environment, including
      traditional norms and values, and social-pressure from peers and adults.
      Learners' most pressing needs and desires to access condoms and SRHR-services in
      school concerned respect, privacy and confidentiality of such service provision.
      Implementation of DBE's policy must be preceded by an evidence-informed advocacy
      campaign to debunk myths about the risk of increased sexual activity, to advocate
      for why such services are needed, to shift societal norms towards open discussion
      of adolescent SRHR and to grapple with the juxtaposition of being legally
      empowered but socially inhibited to protect oneself from HIV, STIs and early
      pregnancy. Provision of condoms and other SRHR-services in schools must be
      sensitive to learners' privacy and confidentiality to minimise stigma and
      discrimination.

PMID- 28509571
TI  - Numerical Study of Novel Ratiometric Sensors Based on Plasmon-Exciton Coupling.
AB  - We numerically studied the optical properties of spherical nanostructures made of
      an emitter core coated by a silver shell through the generalized Mie theory. When
      there is a strong coupling between the localized surface plasmon in the metallic
      shell and the emitter exciton in the core, the extinction spectra exhibit two
      peaks. Upon adsorption of analytes on these core-shell nanostructures, the
      intensities of the two peaks change with opposite trends. This property makes
      them potential sensitive ratiometric sensors. Molecule adsorption on these
      nanostructures can be quantified through a very simple optical configuration
      likely resulting in a much faster acquisition time compared with systems based on
      the traditional metal nanoparticle surface plasmon resonance (SPR) biosensors.

PMID- 28509572
TI  - Effect of silibinin-loaded nano-niosomal coated with trimethyl chitosan on miRNAs
      expression in 2D and 3D models of T47D breast cancer cell line.
AB  - Silibinin is a natural flavonoid with a strong antioxidant property and weak
      cytotoxic activity. It has demonstrated anti-tumoural activity against many types
      of malignancies; however, due to its hydrophobic structure, it has poor water
      solubility, bioavailability and permeability across intestinal epithelial cells.
      To improve the effect of silibinin, we have vehiculated silibinin by a highly
      stable niosomal nanostructure based on a Span 60/cholesterol (CH)/N-trimethyl
      chitosan (TMC) system in order to study its potential application for the
      delivery of silibinin in T47D cultured under three-dimensional (3D) and two
      dimensional (2D) conditions. To study the effect of nanodrug on miRNAs
      expression, we evaluated quantitative expression of miRNA-21 and miRNA-15a as
      well as miR-141 and miR-200c which act as oncogene and tumour suppressors by real
      time PCR. Results demonstrated that the mechanism of nanodrug action as well as
      the response of tumour cells differed in 3D culture as compared to 2D. Delivery
      of silibinin-loaded niosomes coated with TMC was found to be more effective in
      inhibiting the growth of tumour cells and inducing apoptosis than free silibinin
      administration. In silibinin-treated cells, death occurred in a dose- and time-
      dependent manner by induction of apoptosis and alteration of the cell cycle. Real
      time PCR analysis revealed a decrease in miR-21, miR-15a and miR-141while
      increase in miR-200c expression levels was observed in silibinin-treated cells
      relative to the levels in the untreated cells. The results show that nanodrug
      delivery was more effective than free silibinin administration in changing the
      level of miRNAs expression in cancer cells. Therefore, niosomal nanostructure
      with TMC could be a suitable vehicle for hydrophobic compounds, such as
      silibinin, by improving their action in cancer therapy.

PMID- 28509574
TI  - Improving the Early Initiation of Breastfeeding: The WHO-UNICEF Breastfeeding
      Advocacy Initiative.

PMID- 28509573
TI  - Adverse Events of Atomoxetine in a Double-Blind Placebo-Controlled Study in
      Children with Autism.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) symptoms, including
      inattention and over activity, occur in approximately one-third of children with
      autism spectrum disorder (ASD). We describe the rate and duration of adverse
      events in a randomized controlled trial of atomoxetine (ATX) and parent training
      (PT) for ADHD symptoms and noncompliance in children with ASD. METHODS: We
      conducted a 10-week, double-blind, 2 * 2 trial of ATX and PT with 128 children
      (ages 5-14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6
      weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8
      mg/(kg.day) and maintained for an additional 4 weeks. An average of seven PT
      sessions were conducted in the two PT arms. Adverse events (AEs) were assessed
      through parent ratings of common symptoms on a seven-point Likert severity scale
      and through direct interviews with study medical staff. RESULTS: ATX was
      associated with decreased appetite and fatigue, but was otherwise well tolerated.
      Most reported AEs lasted 4 weeks or less. Unlike reports with typically
      developing (TD) children, there were no concerns with QTc changes or suicidal
      ideation. CONCLUSIONS: This study extends the findings of previous studies of ATX
      in ASD by documenting that the type of AEs was similar to that of TD children,
      with no significant safety concerns.

PMID- 28509575
TI  - Haploidentical hematopoietic stem cell transplantation with myeloablative
      conditioning regimen could serve as an optional salvage therapy for younger
      patients with refractory or relapsed aggressive non-Hodgkin lymphoma.

PMID- 28509576
TI  - HER2 positivity may confer resistance to therapy with paclitaxel in breast cancer
      cell lines.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are short non-coding single-stranded RNAs.
      Involving in post-transcriptional gene silencing, miRNAs are thought to play
      important roles in many cancers such as breast cancer. Paclitaxel is used widely
      in the treatment of breast cancer. In this study, we investigated the effect of
      paclitaxel treatment on the expression levels of two oncomirs (oncomiRs), miR-21
      and miR-203, in breast cancer cell lines. MATERIALS AND METHODS: MTT assay was
      performed to determine IC50 of paclitaxel for human breast cancer cell lines
      including MCF-7, MDA-MB-231, SKBR3 and BT-474. After RNA extraction and cDNA
      synthesis, the expression levels of miRNAs were then quantitatively evaluated
      using real-time PCR. RESULTS: Our results showed that after treatment, the
      expression levels of both miR-21 and miR-203 were significantly increased in HER2
      positive cell lines, BT-474 and SKBR3. HER2-negative cell lines, MCF-7 and MDA-MB
      231, in contrast had significantly decreased expression of both assessed
      oncomiRs. CONCLUSION: Our results showed that the expression levels of oncomiRs
      were increased in HER-2 positive breast cancer cells and this finding is in line
      with previous studies. Our findings present a probable mechanism of resistance
      against paclitaxel chemotherapy in HER2-positive breast cancers.

PMID- 28509577
TI  - Alexithymia, suicidal ideation and health-risk behaviours: a survey of Canadian
      men.
AB  - OBJECTIVE: Restricted emotional abilities may present significant implications
      for men's health. The purpose of this study was to examine the relationship
      between alexithymia and several health-risk behaviours: substance misuse,
      aggressive and risky behaviours and suicidal ideation. METHODS: A nationally
      representative sample of 1000 Canadian men responded to a survey containing
      measures of alexithymia, maladaptive coping behaviours, suicidal ideation and
      depressive symptoms. A series of hierarchical regressions were conducted using
      alexithymia as the predictor variable and each health-risk behaviour as the
      criterion variable, controlling for depressive symptom severity. RESULTS:
      Alexithymia was found to be significantly associated with drug use, alcohol use,
      angry/aggressive behaviour and risk-taking behaviour - as well as suicidal
      ideation - beyond the effects of depressive symptoms. CONCLUSIONS: The findings
      provide evidence for the link between alexithymia and several problematic
      behaviours that pose risks to men's health.

PMID- 28509578
TI  - The burden of hepatorenal syndrome among commercially insured and Medicare
      patients in the United States.
AB  - BACKGROUND: This study evaluated the characteristics, healthcare resource
      utilization (HCRU), and costs, from the payer perspective, of hepatorenal
      syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality
      was assessed as a secondary outcome. METHODS: Patients were identified from
      claims databases of commercially insured patients (OptumHealth Care Solutions
      Inc.) in 1998-2014 and Medicare beneficiaries in 2009-2013 (5% Standard Analytic
      Files). At the time of their first inpatient admission ("index date") with an HRS
      diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18-64
      and Medicare patients must be aged 65 and older. RESULTS: A total of 784
      commercially insured and 1061 Medicare HRS patients met the sample selection
      criteria. Patients were disproportionately male (commercial: 63.0%; Medicare:
      57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare
      patients. Within the first 30 days, the average hospital length of stay (LOS) was
      12.3 days among commercially insured and 10.8 days among Medicare patients. Based
      on Kaplan-Meier analyses, 36% of commercially insured and 26% of Medicare
      patients were readmitted within the next 30 days. During follow-up, many patients
      received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant
      (commercial: 10.7%; Medicare: 1.6%). Average costs within the 90 day follow-up
      were $157,665 for commercially insured and $48,322 for Medicare patients, with
      68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost
      driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of
      costs), with differences between the populations consistent with lower mortality,
      higher dialysis rates, and higher transplant rates (both liver and kidney) among
      the commercially insured. Using US population and prevalence statistics, these
      results suggest that HRS imposes an annual total direct medical cost burden of
      approximately $3.0-$3.8 billion to payers over the period. CONCLUSIONS: HRS
      imposes a significant economic burden.

PMID- 28509579
TI  - Findings of Cognitive Impairment at High Altitude: Relationships to Acetazolamide
      Use and Acute Mountain Sickness.
AB  - : Phillips, Lara, Buddha Basnyat, Yuchiao Chang, Erik R. Swenson, and N. Stuart
      Harris. Findings of cognitive impairment at high altitude: relationships to
      acetazolamide use and acute mountain sickness. High Alt Med Biol. 18:121-127,
      2017. OBJECTIVE: Acute mountain sickness (AMS) is defined by patient-reported
      symptoms using the Lake Louise Score (LLS), which provides limited insight into
      any possible underlying central nervous system (CNS) dysfunction. Some evidence
      suggests AMS might coexist with altered neural functioning. Cognitive impairment
      (CI) may go undetected unless a sensitive test is applied. Our hypothesis was
      that a standardized test for mild CI would provide an objective measure of CNS
      dysfunction, which may correlate with the symptoms of AMS and so provide a
      potential new tool to better characterize altitude-related CNS dysfunction. We
      compared a cognitive screening tool with the LLS to see if it correlated with CNS
      dysfunction. METHODS: Adult native English-speaking subjects visiting Himalayan
      Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927
      ft) were recruited. Subjects were administered the LLS and a slightly modified
      version of the environmental Quick mild cognitive impairment screen (eQmci).
      Medication use for altitude illness was recorded. Scores were compared using the
      Spearman's correlation coefficient. Data also included medication use. RESULTS:
      Seventy-nine subjects were enrolled. A cut-off of three or greater was used for
      the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were
      22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria
      for CI. There was a weak correlation (r2 = 0.06, p = 0.04) between eQmci score
      and LLS. In matched subjects with identical LLS, recent acetazolamide use was
      associated with significantly more CI. CONCLUSION: Field assessment of CI using a
      rapid standardized tool demonstrated that a substantial number of subjects were
      found to have mild CI following rapid ascent to 3520-4550 m (11,548-14,927 ft).
      The weak correlation between the LLS and eQmci suggests that AMS does not result
      in CI. Use of acetazolamide appears to be associated with CI at all levels of AMS
      severity.

PMID- 28509580
TI  - Use of minimal residual disease assessment in the treatment of chronic
      lymphocytic leukemia.
AB  - Progress in chronic lymphocytic leukemia (CLL) therapies has extended greatly the
      length and depth of remission, with the goal of treatment advancing towards a
      cure for some patients. Accordingly, clinical endpoints must evolve to capture
      these outcomes, and to provide faster access to novel therapies. Minimal residual
      disease (MRD) is an important endpoint representing more accurately the depth of
      remission than complete response (CR), and is highly prognostic of progression
      free survival (PFS) and overall survival (OS). MRD could be considered a key
      outcome of clinical trials and, as a surrogate for PFS, could identify the most
      cost-effective and durable treatment sequencing. MRD testing could also determine
      which patients would benefit from additional therapy and, accordingly, ascertain
      when therapy should be stopped earlier, to reduce toxicity and increase treatment
      free intervals. Our article discusses possible uses of MRD in the modern era of
      CLL, including its definition, measurement, and value as a surrogate endpoint in
      clinical trials, and its potential roles in clinical practice.

PMID- 28509581
TI  - Dexamethasone distribution characteristic following controllable continuous sub
      tenon drug delivery in rabbit.
AB  - Drug delivery systems are required to be safe, minimally invasive and effectively
      delivery drug to the target tissues. But delivery drugs to the eye has not yet
      satisfied this need. Here, we focused on examining the distribution of
      dexamethasone (DEX) in ocular and plasmic samples following controllable
      continuous sub-Tenon drug delivery (CCSDD) of dexamethasone disodium phosphate
      (DEXP) in rabbit, and to compare that with two traditional routes:
      subconjunctival injection and intravenous injection. The DEX concentration was
      analyzed by Shimadzu LC-MS 2010 system. In CCSDD group, during observed 24 h, the
      mean DEX level in collected samples from highest to lowest following in order:
      sclera, cornea, retina/choroid, iris, plasma, aqueous humor, lens and vitreous
      body. In ocular solid tissue, the DEX level in posterior segment is higher than
      in anatomic corresponding anterior segment, but it is opposite in ocular fluid
      tissue. High levels of DEX were maintained at 12 h in the ocular tissue
      immediately after the administration. Even at 24 h, the mean DEX concentration
      was 31.72 ng/ml and 22.40 ng/ml in aqueous and vitreous, respectively. In CCSDD
      group, the ocular DEX exposure (AUC0-24) is much higher and plasma exposure is
      much less than IV group, and it is also similar in SC group except iris. The
      amount of DEX levels are markedly increased in ocular tissues but it yield lower
      plasma levels indicating reduction of systemic absorption by CCSDD. Thus, CCSDD
      is an effective method of delivering DEX into anterior and posterior segment of
      the eye.

PMID- 28509583
TI  - The Influence of Attachment Styles on Sexual Communication Behavior.
AB  - Attachment theory is one of the major theoretical frameworks for understanding
      romantic relationships. Attachment styles are formed through interactions with
      caregivers and shape an individual's expectations of subsequent interpersonal
      relationships. In this study, we examined how attachment styles influence
      participants' ability to communicate with their partners about problems in their
      sexual relationship. A community sample of 81 couples engaged in two video
      recorded discussions, one representing an aspect of the couple's sexual
      relationship where the male partner wanted change and the second representing an
      aspect of the sexual relationship where the female partner wanted change.
      Conversations were then coded, with each person being rated on three positive
      communication dimensions (positive affect, offering solutions, and
      responsiveness) and three negative communication dimensions (hostility, negative
      affect, and unskilled communication behaviors). As predicted, attachment
      avoidance was related to more negative and less positive communication for both
      the individual and his or her partner. Our observational data did not reveal any
      significant effects of attachment anxiety on sexual communication. These results
      can be contrasted with findings from self-report studies that do suggest an
      anxious attachment adversely impacts sexual communication.

PMID- 28509582
TI  - Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via
      reduction of hypoxia-induced P-gp-mediated drug resistance.
AB  - Multiple myeloma (MM) presents a poor prognosis and high lethality of patients
      due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux
      transporter, is upregulated in MM patients post-chemotherapy and is involved in
      the development of drug resistance since many anti-myeloma drugs (including
      proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow
      niche during MM progression and has long been linked to chemoresistance.
      Additionally, hypoxia-inducible transcription factor (HIF-1alpha) was
      demonstrated to directly regulate P-gp expression. We found that in MM patients P
      gp expression positively correlated with the hypoxic marker, HIF-1alpha. Hypoxia
      increased P-gp protein expression and its efflux capabilities in MM cells in
      vitro using flow cytometry. We reported herein that hypoxia-mediated resistance
      to carfilzomib and bortezomib in MM cells is due to P-gp activity and was
      reversed by tariquidar, a P-gp inhibitor. These results suggest combining
      proteasome inhibitors with P-gp inhibition for future clinical studies.

PMID- 28509584
TI  - The influence of the crutch setup on stability and weight-bearing parameters in
      post total hip replacement surgery patients during quiet standing.
AB  - PURPOSE: The purpose of this study is to evaluate the influence of the crutch
      setup on standing, in post total hip replacement (THR) surgery patients.
      MATERIALS AND METHODS: Thirty patients after THR were randomly assigned to
      walking with the elbow flexed (EF) or elbow straight (ES) crutch setup. Subjects
      were asked to stand on a force platform in a comfortable position with the crutch
      positioned on the unaffected side, facing forward for 10 seconds. Centre of
      pressure total path and maximal excursion were evaluated in both medio-lateral
      and anterior-posterior planes. Difference in the asymmetry of left/right acromial
      height, measured with and without the crutch, was calculated (ACdiff). Percentage
      of body weight borne by the crutch (Fcr), symmetry (SIload) between operated and
      healthy limbs loading during the trial, together with shoulder forces and moments
      were measured. RESULTS: No significant differences between the two groups (p >
      .05) were found for stability parameters. ACdiff, Fcr and shoulder load increased
      significantly (p < .05) in EF group compared to ES group. In addition leg loading
      symmetry was significantly reduced in the EF group. CONCLUSIONS: The present
      study showed that the ES setup reduced the force borne by the crutch, the load on
      the shoulder joint and it minimized postural and loading asymmetries when
      compared to EF setup. Conversely, postural stability was not influenced by the
      crutch setup. Implications for Rehabilitation Static posture and weight-bearing
      parameters are influenced by crutch setup during quiet standing. Crutch setup
      does not influence postural stability. Adjusting the crutch according to the
      elbow straight setup reduces the force borne by the crutch and the asymmetry in
      lower limbs loading. Forces and moments at the shoulder joint were reduced for
      the elbow straight setup group.

PMID- 28509586
TI  - Long-term persistent donor-recipient mixed chimerism without disease recurrence
      after myeloablative single-unit cord blood transplantation in adult acute myeloid
      leukemia following myelodysplastic syndrome.

PMID- 28509585
TI  - Identification of a novel fusion TBL1XR1-PDGFRB in a patient with acute myeloid
      leukemia harboring the DEK-NUP214 fusion and clinical response to dasatinib.

PMID- 28509587
TI  - Link protein N-terminal peptide and fullerol promote matrix production and
      decrease degradation enzymes in rabbit annulus cells.
AB  - PURPOSE: Intervertebral disc degeneration is a major cause of back pain. Novel
      therapies for prevention or reversal of disc degeneration are needed. It is
      desirable for potential therapies to target both inflammation and matrix
      degeneration. MATERIALS AND METHODS: The combined regenerative potential of link
      protein N-terminal peptide (LN) and fullerol on annulus fibrosus (AF) cells was
      evaluated in a 3D culture model. RESULTS: Interleukin-1alpha (IL-1alpha)-induced
      AF cell degeneration was counteracted by fullerol, LN, and fullerol + LN, with
      the latter having the greatest effect on matrix production as evaluated by real
      time polymerase chain reaction and glycosaminoglycan assay. IL-1alpha-induced
      increases in pro-inflammatory mediators (interleukin-6 and cyclooxygenase-2) and
      matrix metalloproteinases (MMP-1, -2, -9, and -13) were also counteracted by
      fullerol and LN. CONCLUSION: Our data demonstrate that LN and fullerol
      individually, and in combination, promote matrix production and have anti
      inflammatory and anti-catabolic effects on AF cells.

PMID- 28509588
TI  - PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to
      facilitate the oral delivery efficiency.
AB  - The natural product berberine (BBR), present in various plants, arouses great
      interests because of its numerous pharmacological effects. However, the further
      development and application of BBR had been hampered by its poor oral
      bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles
      (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent
      evaporation method for enhancing the oral BBR efficiency. The advantage of this
      new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR
      SPC) could be used to enhance the liposolubility of BBR and improve the affinity
      with the biodegradable polymer to increase the drug-loading capacity and
      controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA
      NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4
      times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our
      knowledge, this is the first report on using polymer material for effective
      encapsulation of BBR to improve its oral bioavailability. The prepared BBR
      delivery systems demonstrated a uniform spherical shape, a well-dispersed core
      shell structure and a small particle size (149.6 +/- 5.1 nm). The
      crystallographic and thermal analysis has indicated that the BBR dispersed in the
      PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the
      enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR
      SPC was ~343% compared with that of BBR. These positive results demonstrated that
      PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug
      delivery of BBR.

PMID- 28509589
TI  - Characteristics and Expression Profile of KRT71 Screened by Suppression
      Subtractive Hybridization cDNA Library in Curly Fleece Chinese Tan Sheep.
AB  - As an important commercial trait for sheep, curly fleece has a great economic
      impact on production costs and efficiency in sheep industry. To identify genes
      that are important for curly fleece formation in mammals, a suppression
      subtractive hybridization analysis was performed on the shoulder skin tissues
      exposed to two different growth stages of Chinese Tan sheep with different
      phenotypes (curly fleece and noncurling fleece). BLAST analysis identified 67
      differentially expressed genes, of which 31 were expressed lower and 36 were
      expressed higher in lambs than in adult sheep. Differential expressions of seven
      randomly selected genes were verified using quantitative real-time polymerase
      chain reaction (qRT-PCR). KRT71 gene was selected for further study due to its
      high correlation with the curly hair phenotype in various mammal species. Semi
      qPCR showed distinctively high expression of KRT71 in skin tissues. Moreover,
      qPCR result showed a significantly higher expression of KRT71 in curly fleece
      than noncurling Tan sheep. The luciferase assay and electrophoresis mobility
      shift assay showed that there were transcription factor binding sites in the
      promoter region of KRT71 related to the differential expression of KRT71 at the
      two growth stages of Tan sheep. Online bioinformation tools predicted MFZ1 as a
      transcriptional factor that regulates the expression of KRT71. These studies on
      KRT71 gene revealed some mechanisms underlying the relationship between the KRT71
      gene and the curly fleece phenotype of Tan sheep.

PMID- 28509590
TI  - Health care costs associated with Australian tertiary inflammatory bowel disease
      care.
AB  - INTRODUCTION: We aimed to describe the total costs of illness for IBD patients
      and compare the costs of patients with active disease to those with inactive
      disease. MATERIALS AND METHODS: Resource use for IBD management was itemized for
      attributable costs (AUD) among all IBD patients over a 12-month period at an
      Australian hospital. RESULTS: One hundred and eighty-three patients were included
      (87 ulcerative colitis (UC); 93 Crohn's disease (CD); three IBD-unclassified).
      The median (IQR) annual overall cost was higher in the CD versus UC group
      ($15,648 versus $5017; p < .001). The difference in cost between CD and UC was
      influenced by the difference in outpatient costs for CD patients $9602 ($4311
      $29,805) versus $4867 ($3220-$7249), p < .001). The cost of treating patients
      with active disease was $3461 ($1607-$11,771) and was higher in the CD versus the
      UC group ($6098 ($2168-$16,471) versus $1638 ($1401-$3767); p = .026) and was
      influenced by inpatient admissions. The cost of treating patients in remission
      was $2090 ($1552-$12,954) and was higher in the CD versus the UC group [$7977
      ($1579-$14,304) versus $1848 ($1508-$6601); p = .236]. CONCLUSIONS: There is a
      discrepancy in costs of inpatient versus outpatient IBD management and treating
      active disease compared with disease in remission. Proactive care may help
      prevent disease reaching a severity whereby reactive management of active disease
      is required.

PMID- 28509591
TI  - Current Practice "Constraints" in the Uptake and Use of Intensive Upper Extremity
      Training: A Canadian Perspective.
AB  - BACKGROUND: Intensive upper extremity training (IUET) has demonstrated efficacy
      in clinical and functioning outcomes in children with hemiplegia. However,
      implementation in the clinical context requires novel service models and
      knowledge translation. AIMS: To map implementation of IUET in Canada, to identify
      factors associated with the implementation and best practices for implementation.
      METHODS: Mixed-methods design; descriptive statistics, chi-square tests.
      Individual phone interviews and focus groups with purposeful sampling. Thematic
      analysis; telephone surveys with managers of 31 pediatric rehabilitation centers
      across Canada. Four focus groups across Canada and one in the Netherlands.
      RESULTS: Implementation of IUET group interventions is limited in Canada (7/31).
      Barriers included beliefs and values related to evidence-based practice,
      opportunities for continuing education, researchers-clinicians partnerships,
      access to scientific literature, and the presence of a champion. Pressure from
      parents and media presenting IUET as a novel and effective therapy, support and
      flexibility of families, having the critical mass of clients and a managerial
      willingness to accommodate new ideas and restructure service provision were some
      facilitators. CONCLUSIONS: Uptake of the evidence requires many steps described
      in the knowledge translation cycle. Factors identified in the study could be
      considered in most clinical settings to facilitate the uptake of research
      evidence for IUET.

PMID- 28509592
TI  - Molecular modeling and structure-activity relationships for a series of
      benzimidazole derivatives as cruzain inhibitors.
AB  - AIM: Chagas disease is endemic in Latin America and no effective treatment is
      available. Efforts in drug research have focused on several enzymes from
      Trypanosoma cruzi, among which cruzain is a validated pharmacological target.
      METHODOLOGY: Chemometric analyses were performed on the data set using the
      hologram quantitative structure-activity relationship, comparative molecular
      field analysis and comparative molecular similarity index analysis methods.
      Docking simulations were executed using the crystallographic structure of cruzain
      in complex with a benzimidazole inhibitor. The top-scoring enzyme-inhibitor
      complexes were selected for the development of the 3D quantitative structure
      activity relationship (QSAR) models and to assess the inhibitor binding modes and
      intermolecular interactions. RESULTS: Benzimidazole derivatives as cruzain
      inhibitors were used in molecular docking and QSAR studies. Significant
      statistical indicators were obtained, and the best models demonstrated high
      predictive ability for an external test set (r 2pred = 0.65, 0.94 and 0.82 for
      hologram QSAR, comparative molecular field analysis and comparative molecular
      similarity index analysis, respectively). Additionally, the graphical information
      of the chemometric analyses demonstrated substantial complementarity with the
      enzyme-binding site. CONCLUSION: These results demonstrate the relevance of the
      QSAR models to guide the design of structurally related benzimidazole derivatives
      with improved potency.

PMID- 28509593
TI  - Impact of pharmacokinetics on the toxicity and efficacy of clofarabine in
      patients with relapsed or refractory acute myeloid leukemia.
AB  - Common side effects of clofarabine (CFB) are liver toxicity, particularly a
      transient elevation of transaminases and skin toxicity. We studied the
      correlation of pharmacokinetic (PK) parameters with these toxicities and the
      efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia.
      Clofarabine PK parameters showed large inter-individual variability. A higher CFB
      area under the curve was significantly associated with higher transaminase levels
      (p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated
      CFB dosage, baseline AST, and glomerular filtration rate (GFR)). No significant
      association could be found between maximum concentration and the liver toxicity
      parameters. The occurrence of skin toxicity and the response to re-induction
      chemotherapy evaluated at day 15 were also not associated with PK. In conclusion,
      a higher individual CFB exposure is associated with increased liver toxicity
      reflected by elevated liver enzymes, without having an impact on anti-leukemic
      efficacy.

PMID- 28509594
TI  - G-CSF improves safety when you start the day after autologous transplant in
      multiple myeloma.

PMID- 28509595
TI  - Phase II study of intensified rituximab induction and maintenance for low grade B
      cell lymphoma.
AB  - Rituximab has markedly improved the outcomes of B cell lymphoma, and its
      maintenance has been shown to be beneficial in low grade B cell lymphoma (LGBCL).
      We conducted a multicenter, phase II trial of intensive rituximab induction and
      maintenance therapy for LGBCL to optimize the rituximab monotherapy. Patients
      with newly diagnosed or rituximab naive relapsed LGBCL received 8 weekly
      rituximab as induction, then continued maintenance therapy with rituximab for 4
      weeks at 6-month intervals. The primary endpoint was the overall response rate
      (ORR). Forty-five patients were enrolled from 2005 to 2009 and 36 were eligible.
      The ORR was 83.3% (30/36) with a complete response rate of 72.2% (26/36). The 3
      year progression-free survival (PFS) was 76.7% with a median follow-up of 43.0
      months. Five grade three toxicities were observed (no grade 4). Our findings
      suggest that this regimen demonstrates high activity with durable PFS and minimal
      toxicity in LGBCL patients.

PMID- 28509596
TI  - Joint moment-angle properties of the hip abductors and hip extensors.
AB  - PURPOSE: Strengthening of hip joint musculature is common in the rehabilitation
      of the lower extremity. However, strength curves for hip abduction and extension
      have not been assessed when varying the position of the knee. The force-length
      properties of the biarticular muscles can be affected when altering the position
      of the knee during the production of hip moments. METHODS: Maximum isometric
      joint moments were measured at four different angles of hip abduction and hip
      extension, at the two knee positions (0 degrees  and 90 degrees ). RESULTS: The
      hip abduction and extension moments decreased as the hip moved from an adducted
      position and flexed position to an abducted position and extended position,
      respectively, resulting in a descending joint moment angle curve for each.
      CONCLUSION: The results indicate that position of the knee does not significantly
      change the normalized peak hip abduction joint moment, but the position of the
      knee does significantly change the normalized peak hip extension joint moment.
      This provides a baseline reference of hip joint moment production and can be
      utilized when assessing a population with a pathology or prescribing
      rehabilitative exercises.

PMID- 28509597
TI  - Use of technological aids and interpretation services among children and adults
      with hearing loss.
AB  - OBJECTIVES: The technological development of communication aids for people with
      hearing loss has progressed rapidly over the last decades. Quality has improved
      and the number of different types of aids has increased. However, few studies
      have examined the prevalence of technology use and interpreting services use
      among people with hearing loss as they relate to demographic characteristics of
      this population. DESIGN: This study reports from national surveys of children and
      adults with hearing loss. Use of hearing aids, cochlear implants, other aids and
      interpreting services were analysed with regard to gender, age, degree of hearing
      loss, mode of communication, having an additional disability, level of
      educational achievement among adults, and whether or not children lived together
      with both of their parents. STUDY SAMPLE: 269 children (0-15 years of age) and
      839 adults (16-65 years of age). RESULTS: Differences in technology and service
      use were associated with age, degree of hearing loss, and mode of communication
      among children and adults, and gender and level of educational achievement among
      adults. CONCLUSION: Individual and social factors have an impact on technological
      hearing aid and interpreter use. More research about individual differences and
      clinical implications of support services is needed.

PMID- 28509599
TI  - A review of dosimetric and toxicity modeling of proton versus photon craniospinal
      irradiation for pediatrics medulloblastoma.
AB  - BACKGROUND: Craniospinal irradiation (CSI) is the standard radiation therapy
      treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI)
      delivers significant dose to surrounding normal tissue (NT). Research into
      pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of
      exploiting the potential to reduce NT dose and associated post-treatment
      complications. This review aims to compare treatment outcomes of pediatric
      medulloblastoma patients between Proton- and Photon-CSI treatments. MATERIAL AND
      METHODS: A search and review of studies published between 1990 and 2016 comparing
      pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects -
      normal organ sparing and target coverage; normal organ dysfunction and second
      malignancy risks - was completed. RESULTS: Fifteen studies were selected for
      review and the results were directly compared. Proton-CSI reported improved out
      of-field organ sparing while target coverage improvements were inconsistent.
      Normal organ dysfunction risks were predicted to be lower following Proton-CSI.
      Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on
      several different risk models. CONCLUSIONS: Proton-CSI conferred better treatment
      outcomes than Photon-CSI for pediatric medulloblastoma patients. This review
      serves to compare the current literature in the absence of long-term data from
      prospective studies.

PMID- 28509598
TI  - Elevated dopamine D1 receptor availability in striatum of Gottingen minipigs
      after electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an
      effective antidepressant. We hypothesized that the beneficial effects of ECT are
      mediated by increased dopaminergic neurotransmission, in which the baseline
      activity of D1 receptors may predict the response to ECT. We established a novel
      model of brain stimulation in Gottingen minipigs based on the protocol of ECT
      applied in humans. With positron emission tomography (PET), we determined a
      measure of dopaminergic neurotransmission with the dopamine D1 receptor
      antagonist [11C]SCH23390. Seven minipigs were anesthetized and completed PET at
      baseline, prior to the onset of ECT treatment, and at 24-48 h and 8-10 days after
      the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5
      week period. In all pigs, the binding of [11C]SCH23390 to striatal D1 receptors
      had increased by 24-48 h after ECT, and in most, binding returned towards
      baseline at 8-10 days. Increased binding was observed in inverse proportion to
      baseline binding rates. Increased binding to dopamine D1 receptors suggests
      facilitation of dopaminergic neurotransmission, which may contribute to the
      therapeutic effects of ECT. Importantly, the baseline binding capacity of D1
      receptors predicts the magnitude of increased binding, up to a maximum binding
      capacity.

PMID- 28509600
TI  - How to Pronounce.

PMID- 28509602
TI  - A Remote View.

PMID- 28509601
TI  - The unattainable criteria for new infant vaccines.
AB  - BACKGROUND: In 2013, the US Advisory Committee on Immunization Practices (ACIP)
      opted against adding meningococcal vaccines to the infant schedule due to poor
      cost-effectiveness. This raises a policy question: if meningococcal disease is
      too rare to justify routine vaccination, are there other vaccine-preventable
      causes of US infant deaths that could be supported? METHODS: We tabulated US
      infant deaths from 2009-2013 using the CDC WONDER database. These causes of death
      were then categorized into one of 3 categories: 1) vaccine-preventable using
      currently available interventions; 2) potentially vaccine-preventable within the
      next 10 years; and 3) not preventable. RESULTS: From 19.8 million births (3.9
      million/year), ~122,000 infants died (0.62%). Of these, 181 (0.15% of all deaths)
      were preventable using currently available vaccines, while an additional 779 were
      categorized as potentially preventable in the next 10 y. By exclusion, 121,040
      (99.2%) were judged 'not vaccine-preventable'. Meningococcal deaths contributed
      at most 0.03% of all infant deaths, but accounted for 17-34% of current vaccine
      preventable deaths. CONCLUSIONS: The low number of vaccine-preventable deaths in
      the US makes it increasingly difficult to justify the introduction of any new
      infant vaccines.

PMID- 28509603
TI  - Reaching Beyond Doing a Survey and a Few Interviews: The Importance of
      Maintaining Rigor & Validity in Prehospital Qualitative Research.

PMID- 28509604
TI  - Moving forth: Imagining physiotherapy education differently.
AB  - Contemporary and future physiotherapists are, and will be, presented with
      challenges different to their forebears. Yet, physiotherapy tends to remain tied
      to historical ways of seeing the world: these are passed down to generations of
      physiotherapy graduates. These historical perspectives privilege particular
      knowledge and skills so that students gain competency for graduation. However,
      contemporary practice is inherently more complex than the focus on knowledge and
      skills would have us believe. Professional life requires students to develop the
      capability to deal with uncertain and diverse futures. This paper argues that
      physiotherapy needs to think differently about entry-level education; the focus
      on knowledge and competencies that has been the mainstay in physiotherapy
      education must now be understood in the context of an education that embraces
      knowing, doing, being. Two educational frameworks are offered in support of this
      argument - threshold concepts and ways of thinking and practicing (WTP). Taken
      together, these ideas can assist physiotherapy to think in fresh ways about
      disciplinary learning. Threshold concepts and WTP help to understand the nature
      of a discipline: its behaviors, culture, discourses, and methods. By
      interrogating the discursive aspects of the discipline, physiotherapy educators
      will be better placed to provide more relevant preparation for practice.

PMID- 28509605
TI  - Safety and immunogenicity of Bio PoxTM, a live varicella vaccine (Oka strain) in
      Indian children: A comparative multicentric, randomized phase II/III clinical
      trial.
AB  - Varicella or chickenpox is a highly contagious disease with a high secondary
      attack rate. Almost 30% of Indian adolescents lack protective antibodies against
      varicella, emphasizing the need of routine varicella immunization. The Oka VZV is
      a well-established, safe and efficacious vaccine strain that is highly
      immunogenic and produces lifelong protective immunity. The present multicentric,
      open label, randomized, controlled Phase II/III study, compared the Bio PoxTM
      (indigenous investigational vaccine) with a licensed vaccine, VarivaxTM [a][a]
      Please note that this article refers to the product named VARIVAX as manufactured
      by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB
      Life Sciences Limited, Mumbai, and not the product VARIVAX(r) owned by Merck
      Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have
      asked us to make clear that the product manufactured by Changchun Keygen
      Biological Products Ltd. is unrelated to and is not sponsored, endorsed or
      otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and
      immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort
      I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were
      measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit.
      Seroconversion percentage in children having pre-vaccination anti VZV IgG titer
      <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio PoxTM and 77% for VarivaxTM
      (p = 0.692). The seroconversion rate in the group receiving Bio PoxTM was non
      inferior to the group that received VarivaxTM. There were mild local reactions
      for both the vaccines; none of the patient had fever or required hospitalization
      or medication. The Bio PoxTM was found to be safe and immunogenic in children
      against VZV infection.

PMID- 28509606
TI  - Combined immunotherapy of breast cancer with EGF and VEGF vaccines from DNA
      shuffling in a mouse model.
AB  - AIM: Development of EGF and VEGF vaccines with high antigenicity for combined
      immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast
      cancer. METHOD: EGF genes from mouse, human and chicken were randomly assembled
      to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR,
      SDS-PAGE and immunization for combined immunotherapy of breast cancer with a
      previously constructed chimeric VEGF vaccine from shuffling. RESULTS: Combined
      vaccination with chimeric EGF and VEGF from shuffling could induce high titer of
      antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and
      improve the survival rate of mice with breast cancer. CONCLUSION: Combined
      vaccination with EGF and VEGF from shuffling showed better immunotherapy on EGF
      EGFR signaling-dependent epithelial tumors such as breast cancer than the single
      agent EGF vaccination.

PMID- 28509607
TI  - Intravacc.

PMID- 28509608
TI  - Differential diagnosis and recovery of acute bilateral foot drop in a patient
      with a history of low back pain: A case report.
AB  - BACKGROUND AND PURPOSE: Acute bilateral foot drop is rare and may be due to
      peripheral or central lesions. The purpose of this case report was to describe
      the differential diagnosis and recovery of a patient with low back pain (LBP)
      that awoke with bilateral foot drop. CASE DESCRIPTION: A 39-year-old man with a
      history of LBP awoke with a steppage gait pattern. Spinal imaging and tapping
      were negative for sinister pathologies. A subsequent history taken by the
      physical therapist uncovered that the patient had previously taken a narcotic and
      slept in a kneeling position to relieve his LBP. Strength and sensory testing
      revealed isolated impairments in the fibular nerve distribution, and bilateral
      fibular palsy was suspected and later confirmed with electrophysiological
      studies. Surgical fibular nerve decompression was performed, and the patient
      underwent physical therapy. OUTCOMES: Five months later the patient demonstrated
      antigravity strength and a partial return of sensation. By 17 months, his Lower
      Extremity Functional Scale had improved from 17/80 to 78/80, revealing a near
      complete recovery. DISCUSSION: The patient's history of LBP was a "red herring"
      that delayed the diagnosis and caused undue stress to the patient. This case
      stresses the importance of a thorough history and clinical examination.

PMID- 28509610
TI  - Development of culture-sensitive clinical teacher evaluation sheet in the
      Japanese context.
AB  - AIM: Many instruments for evaluating clinical teaching have been developed,
      albeit most in Western countries. This study aims to develop a validated cultural
      and local context sensitive instrument for clinical teachers in an East Asian
      setting (Japan), Japanese Clinical Teacher Evaluation Sheet (JaCTES). METHODS: A
      multicenter, cross-sectional evaluation study was conducted. We collected a total
      of 1368 questionnaires on 304 clinical teachers, completed by residents in 16
      teaching hospitals. The construct validity was examined by conducting a factor
      analysis and using structural equation modeling (SEM). We also assessed the
      reliability using generalizability analysis and decision study. RESULTS:
      Exploratory factor analysis resulted in three-factor (role model, teaching
      activities, and accessibility) model including 18 items. Confirmatory factor
      analysis was performed, using SEM. The comparative fit index was 0.931 and the
      root mean square error of approximation was 0.087, meaning an acceptable goodness
      of fit for this model. To obtain a reliable dependability-coefficient of at least
      0.70 or higher, 5-8 resident responses are necessary. DISCUSSION AND CONCLUSION:
      JaCTES is the first reported instrument with validity evidence of content and
      internal structure and high feasibility in Japan, an East Asian setting. Medical
      educators should be aware of the local context and cultural aspects in evaluating
      clinical teachers.

PMID- 28509609
TI  - Amyloid- and FDG-PET in sporadic Creutzfeldt-Jakob disease: Correlation with
      pathological prion protein in neuropathology.
AB  - INTRODUCTION: The role of positron emission tomography (PET) in Creutzfeldt-Jakob
      disease is less defined than in other neurodegenerative diseases. We studied the
      correlation between the uptake of 18F-florbetaben and 18F-fluorodeoxyglucose with
      pathological prion protein deposition in histopathology in a case. METHODS: A
      patient with 80 y old with a rapid neurological deterioration with a confirmed
      diagnosis of CJD was studied. PET and MRI studies were performed between 13-20 d
      before the death. A region of interest analysis was performed using Statistical
      Parametric Mapping. RESULTS: MRI showed atrophy with no other alterations. FDG
      PET showed extensive areas of hypometabolism including left frontoparietal lobes
      as well as bilateral thalamus. Correlation between uptake of 18F-florbetaben and
      pathological prion protein deposition was r = 0.786 (p < 0.05). Otherwise,
      correlation between uptake of 18F-FDG and pathological prion protein was r =
      0.357 (p = 0.385). Immunohistochemistry with beta-amyloid did not show amyloid
      deposition or neuritic plaques. CONCLUSIONS: Our study supports the use of FDG
      PET in the assessment of CJD. FDG-PET may be especially useful in cases of
      suspected CJD and negative MRI. Furthermore, this case report provides more
      evidence about the behavioral of amyloid tracers, and the possibility of a low
      affinity binding to other non-amyloid proteins, such as the pathological prion
      protein, is discussed.

PMID- 28509611
TI  - Efficacy of high-resolution cone-beam CT in the evaluation of perforators in
      vertebral artery dissection.
AB  - Introduction A major complication of internal coil trapping for vertebral artery
      dissection (VAD) is medullary infarction associated with perforator occlusion.
      Currently, higher spatial resolution imaging can be obtained with high-resolution
      cone-beam computed tomography (VASO CT), and the efficacy of perforator
      visualization adjacent to VAD was examined. Methods Eight patients who underwent
      internal coil trapping or stent-supported coil embolization underwent VASO CT to
      evaluate perforators around VAD. Visualization of perforators was compared with
      conventional digital subtraction angiography (DSA) and three-dimensional
      rotational angiography (3D-RA). Postoperative MRI was performed in all patients
      to investigate ischemic complications. The relationship between the perforators
      and the infarction was analyzed. Results Perforator visualization was much
      clearer on VASO CT than on 2D DSA or 3D-RA. It was sharp enough to identify each
      perforating artery. Medullary infarctions were detected in two cases. In these
      two cases, each ischemic lesion corresponded to the territory of a perforator
      that was well visualized on VASO CT. The axial view with adjoining tissue
      structures on VASO CT was useful to detect the territories of perforators.
      Conclusions VASO CT is an efficient modality for the detection and identification
      of perforators in the vicinity of VAD. It provides accurate anatomical
      information about the vertebrobasilar system that is useful for the treatment of
      unruptured VAD.

PMID- 28509612
TI  - Defining the phylogenetic position of Amanita species from Andean Colombia.
AB  - Amanita is a worldwide-distributed fungal genus, with approximately 600 known
      species. Most species within the genus are ectomycorrhizal (ECM), with some
      saprotrophic representatives. In this study, we constructed the first
      comprehensive phylogeny including ECM species from Colombia collected in native
      Quercus humboldtii forests and in introduced Pinus patula plantations. We
      included 8 species (A. brunneolocularis, A. colombiana, A. flavoconia, A.
      fuligineodisca, A. muscaria, A. rubescens, A. sororcula, and A. xylinivolva) out
      of 16 species reported for the country, two new reports: A. citrina and A.
      virosa, and a new variety A. brunneolocularis var. pallida. Morphological
      taxonomic keys together with a phylogenetic approach using three nuclear gene
      regions: partial nuc rDNA 28S nuc rDNA internal transcribed spacers ITS1 and ITS2
      and partial translation elongation factor 1-alpha gene (TEF1), were used to
      classify the specimens. Several highly supported clades were obtained from the
      phylogenetic hypotheses obtained by Bayesian inference and maximum likelihood
      approaches, allowing us to position the Colombian collections in a coherent
      infrageneric level and to contribute to the knowledge of local Amanita diversity.

PMID- 28509613
TI  - Impact of a specialty pharmacy case management service on adherence in patients
      receiving oral antineoplastic agents.
AB  - Background Patients receiving treatment with oral antineoplastic agents encounter
      several barriers to adherence, which may include high medication costs, limited
      access to specialty medications, severe adverse effects, complex medication
      regimens, and special handling precautions. Medication nonadherence not only
      reduces the efficacy of drug therapy but also has the potential to increase
      healthcare expenditures due to disease-related hospitalizations. Although several
      previous studies have examined patient adherence to oral antineoplastic agents,
      few have examined the impact of a specialty pharmacy case management service.
      Methods Patient adherence to oral antineoplastic agents was evaluated through a
      retrospective analysis of pharmacy claims data and medical chart reviews. The
      medication possession ratio (MPR) was used to quantitatively measure adherence
      during two 6-month intervals, prior to and following the implementation of a case
      management service. Patients with an MPR greater than or equal to 0.8 were
      categorized as adherent, while those with an MPR less than 0.8 were categorized
      as non-adherent. Results During the first 6-month interval prior to
      implementation of the case management service (n = 40), a cumulative average MPR
      of 0.922 was observed. Following implementation of the case management service (n
      = 56), a non-statistically significant (p = 0.199) increase in MPR to 0.941 was
      identified. For patients categorized as non-adherent, a nonstatistically
      significant (p = 0.214) decrease from 15% to 7% was identified following the
      introduction of the case management service. Conclusion Study results from this
      retrospective review indicate that case management services provided through an
      outpatient specialty pharmacy may have the potential to improve patient adherence
      to oral antineoplastic agents.

PMID- 28509614
TI  - The impact of pharmacist telephone calls after discharge on satisfaction of
      oncology patients: A randomized controlled study.
AB  - Purpose The aim of the study was to determine the impact of telephone follow-up
      calls on satisfaction in oncology patients after hospital discharge. Method A
      randomized controlled study, in which patients were randomized into two groups:
      The experimental group with the telephone follow-up (TFU) calls (intervention)
      and the control group (no intervention). The telephone follow-up call was
      conducted within 72 h after discharge. During the call, patients were asked about
      their medications, namely, whether they received them, understood how to take
      them, and whether they developed any medication-related adverse effect. Both
      groups were contacted by phone two weeks later to assess their satisfaction with
      the discharge medication instructions and the provided pharmaceutical services,
      using the 5-point Likert scale. In addition, hospital records were reviewed for
      emergency room visits and hospital readmissions within 30 days after discharge.
      Results There was no difference in the percentage of patients who reported being
      very satisfied between both the intervention and the control groups (45%
      intervention vs. 48% control, P = 0.68). The mean time of the intervention phone
      call was 3 +/- 1.7 (SD) min. During the telephone follow-up call, medication
      related problems were identified in 20% of the patients. There was no significant
      difference in emergency room visits and hospital readmissions in the intervention
      group vs. control (44% vs. 53%, P = 0.123) and (37% vs. 43%, P = 0.317),
      respectively. Conclusion Telephone follow-up calls conducted by a pharmacist to
      discharged oncology patients did not improve patients' satisfaction, emergency
      room visits or hospital readmissions; however, they helped to identify medication
      related adverse effects in the oncology patients.

PMID- 28509615
TI  - Mining of a phospholipase D and its application in enzymatic preparation of
      phosphatidylserine.
AB  - Phosphatidylserine (PS) is useful as the additive in industries for memory
      improvement, mood enhancement and drug delivery. Conventionally, PS was extracted
      from soybeans, vegetable oils, egg yolk, and biomass; however, their low
      availability and high extraction cost were limiting factors. Phospholipase D
      (PLD) is a promising tool for enzymatic synthesis of PS due to its
      transphosphatidylation activity. In this contribution, a new and uncharacterized
      PLD was first obtained from GenBank database via genome mining strategy. The open
      reading frame consisted of 1614 bp and potentially encoded a protein of 538-amino
      acid with a theoretical molecular mass of 60 kDa. The gene was successfully
      cloned and expressed in Escherichia coli. Its enzymatic properties were
      experimentally characterized. The temperature and pH optima of PLD were
      determined to be 60 degrees C and 7.5, respectively. Its hydrolytic activity was
      improved by addition of Ca2+ at 5 mM as compared with the control. The enzyme
      displayed suitable transphosphatidylation activity and PS could be synthesized
      with L-serine and soybean lecithin as substrates under the catalysis of PLD. This
      PLD enzyme might be a potential candidate for industrial applications in PS
      production. To the best of our knowledge, this is the first report on genome
      mining of PLDs from GenBank database.

PMID- 28509616
TI  - Depersonalization, adversity, emotionality, and coping with stressful situations.
AB  - Depersonalization is defined as persistent or recurrent episodes of feeling
      detached or estranged from a sense of self and the world. This study addressed
      the primary question: Do nonclinical individuals who endorse high symptomatic
      depersonalization have inherently more intense emotional responses, along with
      more childhood adversity and past trauma? In this IRB approved study,
      participants who met clinical levels of depersonalization (n = 43, 16.3%) were
      compared to a group without clinical levels of depersonalization (n = 221,
      83.7%). Adverse childhood experiences, adult traumatic events, emotional
      overexcitability, coping strategies under stress, and anxiety were examined in
      both groups. The variables to assess depersonalization severity included the
      Dissociative Experience Scale-II, Cambridge Depersonalization Scale, and
      Multiscale Dissociation Inventory. The results indicated that clinical levels of
      depersonalization were identified in 16.3% of the sample. The high
      depersonalization group had significantly more adverse childhood experiences, in
      particular, emotional abuse and neglect. They also experienced more adult
      traumatic events, higher levels of anxiety, more emotional overexcitability, and
      they employed a less adaptive emotion-oriented coping strategy under stress. It
      is recommended that treating depersonalization symptoms should include examining
      childhood adversity, especially emotional abuse and neglect. Based on study
      findings, emotion regulation skills should be promoted to help individuals with
      elevated depersonalization manage their emotion-oriented coping strategies,
      anxiety, and emotional overexcitability.

PMID- 28509617
TI  - Intergenerational transmission of traumatization: Theoretical framework and
      implications for prevention.
AB  - Intergenerational transmission of traumatization (ITT) occurs when traumatized
      parents have offspring with increased risk for emotional and behavioral problems.
      Although fetal exposure to the maternal biological milieu is known to be one
      factor in ITT, PTSD-driven parent-child interactions represent an additional
      important and potentially modifiable contributor. The Perinatal Interactional
      Model of ITT presented herein proposes that PTSD leads to social learning and
      suboptimal parent-child interactions, which undermine child regulatory capacity
      and increase distress, largely explaining poor social-emotional outcomes for
      offspring of parents with PTSD. Psychosocial intervention, particularly when
      delivered early in pregnancy, holds the possibility of disrupting ITT.

PMID- 28509618
TI  - Follow-up of patients with thyroglobulin-antibodies: Rising Tg-Ab trend is a risk
      factor for recurrence of differentiated thyroid cancer.
AB  - PURPOSE: Differentiated thyroid cancer is the most common endocrine malignancy.
      Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has
      proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab)
      may interfere with Tg measurement, leading to over or underestimation. It is
      proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet
      few studies define trend and have a long-term follow-up. The objective of our
      study was to investigate the value of a well-defined Tg-Ab trend as a surrogate
      marker for disease recurrence during long-term follow-up. METHODS: We
      retrospectively studied patients treated at the Nuclear Department of the
      University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer
      Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment
      were included. The definition of a rise was >50% increase of the Tg-Ab value in a
      2 year time period. A decline as >50% decrease of the Tg-Ab value. RESULTS:
      Twenty-five patients were included. None of the patients with declining or stable
      Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did
      suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of
      these patients Tg was undetectable. CONCLUSIONS: Tg-Ab trend can be used as a
      crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend
      in Tg-Ab warrants further investigation to detect recurrent disease. Stable or
      declining Tg-Ab levels do not seem to reflect a risk for recurrence.

PMID- 28509620
TI  - The role of social workers in addressing nonmedical needs in primary health care.
AB  - Nonmedical needs are intricately linked to health. Unaddressed nonmedical needs
      often result in poorer health and increased healthcare costs. Although social
      workers are well positioned to address nonmedical needs, their role in healthcare
      environments to address nonmedical needs is limited. The limited role relates to
      a lack of reimbursement streams, which stems from poor articulation about their
      unique contributions. An analysis of a case study in which a social worker using
      AIMS, a protocolized care coordination model, was undertaken to highlight
      specific activities performed by social workers. Implications for patient health
      outcomes and healthcare costs are discussed.

PMID- 28509619
TI  - Japanese Encephalitis Virus Infection Rate and Detection of Genotype I From Culex
      tritaeniorhynchus Collected From Jiangsu, China.
AB  - Information regarding the infection rate and genotype shifts for Japanese
      encephalitis virus (JEV) are important for JE vaccine application. In Jiangsu
      province, China, which is one of the provinces with a high prevalence of JE, JEV
      infection in swine and mosquitoes in certain cities has only been investigated in
      2008-2009. Lianyungang City has one of the highest numbers of JE cases in Jiangsu
      province, and it has a high risk of JEV invasion via migrant birds. JEV infection
      in vectors in Lianyungang City, which has urban and rural parts, has not been
      investigated. In 2015-2016, we collected mosquitoes in cowsheds with ultraviolet
      light traps and detected JEV by reverse transcription-polymerase chain reaction
      (RT-PCR) method in Culex tritaeniorhynchus in Xintan village, Xuzhuang village,
      and Xiaogaozhuang village in Lianyungang City, China. The proportion of positive
      pools, which is calculated by the number of infected pools to the total number of
      pools tested in these villages, were 16.67%, 20.00%, and 4.17%, respectively, and
      the minimum infection rates, which is calculated as the ratio of the number of
      positive pools to the total number of mosquitoes tested, were 3.330/00, 4.000/00,
      and 0.830/00, respectively. Four JEV strains from positive samples were coded as
      LYG-1, LYG-2, LYG-3, and LYG-4, and the complete E genes were sequenced.
      Furthermore, the complete genome of LYG-3 was sequenced. The phylogenetic
      analysis indicated that all the four JEV strains belonged to genotype I-b. This
      is the first report of genotype I JEV strain in Jiangsu province. The high JEV
      infection rate in Culex tritaeniorhynchus indicated a high risk of JE reemergence
      in Lianyungang. The detected JEV strains may have similar antigenicity to that of
      SA14-14-2 according to molecular characters. These findings suggest that the
      vaccine can still be effective in Lianyungang.

PMID- 28509621
TI  - Atherosclerotic vascular diseases have really the same risk factors? Comparison
      between large abdominal aortic aneurysm and obstructive non-coronary arterial
      disease.
AB  - Objectives The purpose of this study was to investigate whether there are
      differences among clinical conditions and traditional atherosclerotic risk
      factors between patients with large abdominal aortic aneurysm and those with
      occlusive non-coronary arterial disease. Methods We clinically examined 519
      patients with asymptomatic abdominal aortic aneurysm and 672 with severe
      obstructive arterial diseases before surgical repair. Results In patients with
      abdominal aortic aneurysm, we identified a clear predominance of males ( p <
      0.001), more alcohol consumers ( p < 0.05), higher values of diastolic blood
      pressure ( p < 0.05), higher values of serum creatinine ( p < 0.005), more
      hyperuricemic patients ( p < 0.005) and less diabetics ( p < 0.001). In patients
      with occlusive atherosclerotic vasculopathies, we observed more smokers ( p <
      0.05), higher systolic blood pressure and more hypertensives ( p < 0.05
      respectively) and a prevalence of hypertriglyceridemia ( p < 0.05). Conclusions
      Patients with abdominal aortic aneurysm were mostly males with diastolic
      hypertension, impaired renal function and less diabetics, while patients with
      occlusive arteriopathy were more smokers, hypertensives and more
      hypertriglyceridemics.

PMID- 28509622
TI  - Attachment insecurity as a mediator of the relationship between childhood trauma
      and adult dissociation.
AB  - This study aimed to investigate whether attachment insecurity mediates the
      relationship between childhood trauma and adult dissociation, specifically with
      regard to individual forms of childhood maltreatment. Psychiatric outpatients who
      visited a specialized trauma clinic (n = 115) participated in the study. Data
      were collected via the Childhood Trauma Questionnaire, Revised Adult Attachment
      Scale, and Dissociative Experience Scale. Structural equation modeling and path
      analysis were performed to analyze the mediating effects of attachment insecurity
      on the relationship between childhood trauma and adult dissociation. Greater
      childhood trauma was associated with higher dissociation, and the relationship
      between them was fully mediated by attachment anxiety. In path analysis of trauma
      subtypes, the effects of emotional abuse, physical abuse, and physical neglect as
      a child on adult dissociation were found to be fully mediated by attachment
      anxiety. The effect of sexual abuse on dissociation was mediated by a synergistic
      effect from both attachment anxiety and attachment avoidance. Regarding emotional
      neglect, a countervailing interaction was discovered between the direct and
      indirect effects thereof on dissociation; the indirect effect of emotional
      neglect on dissociation was partially mediated by attachment insecurity. Specific
      aspects of attachment insecurity may help explain the relationships between
      individual forms of childhood trauma and adult dissociative symptoms. Tailored
      treatments based on affected areas of attachment insecurity may improve outcomes
      among patients with dissociative symptoms and a history of childhood trauma.

PMID- 28509623
TI  - Gastrostomy in patients with prion disease.
AB  - Patients with prion diseases can live for long periods of time in a state of
      akinetic mutism given appropriate management of their symptoms. To study symptom
      support in these cases, we performed gastrostomies on 3 patients with V180I
      genetic Creutzfeldt-Jakob disease (CJD) who had become akinetic and mute, and
      compared them to 14 other similar patients being fed by tube. In the 3
      gastrostomy cases, there were no direct complications due to the gastrostomy or
      tube feeding, nor were there episodes of discontinuation of tube feeding or
      initiation of continuous drip infusion due to severe complications. Antibiotics
      were administered for mild infections, a complication of CJD, with 0.2% and 8.8%
      of the total time after gastrostomy being used for intravenous or transluminal
      administration, respectively. We compared the present patient series with that of
      our previous report statistically, and found that patients undergoing gastrostomy
      required significantly fewer discontinuations of tube feeding than those who did
      not. No significant difference in antibiotic administration was found between
      groups, however. It is our conclusion that gastrostomy should be allowed for
      symptom support in akinetic patients with prion disease, but adequate informed
      consent must be provided to the patient's family.

PMID- 28509624
TI  - The role of evidence-based therapy relationships on treatment outcome for adults
      with trauma: A systematic review.
AB  - OBJECTIVE: The purpose of this paper was to systematically review and synthesize
      the empirical literature on the effects of evidence-based therapy relationship
      (EBR) variables in the psychological treatment for adults who experienced trauma
      related distress. METHOD: Studies were identified using comprehensive searches of
      PsycINFO, Medline, Published International Literature on Traumatic Stress, and
      Cumulative Index to Nursing and Allied Health Literature databases. Included in
      the review were articles published between 1980 and 2015, in English that
      reported on the impact of EBRs on treatment outcome in clinical samples of adult
      trauma survivors. RESULTS: Nineteen unique studies met inclusion criteria. The
      bulk of the studies were on therapeutic alliance and the vast majority found that
      alliance was predictive of or associated with a reduction in various
      symptomotology. Methodological concerns included the use of small sample sizes,
      little information on EBRs beyond alliance as well as variability in its
      measurement, and non-randomized assignment to treatment conditions or the lack of
      a comparison group. CONCLUSIONS: More research is needed on the roles of client
      feedback, managing countertransference, and other therapist characteristics on
      treatment outcome with trauma survivors. Understanding the role of EBRs in the
      treatment of trauma survivors may assist researchers, clinicians, and
      psychotherapy educators to improve therapist training as well as client
      engagement and retention in treatment.

PMID- 28509626
TI  - Custom-compounded bioidentical hormone therapy: why so popular despite potential
      harm? The case against routine use.
AB  - Wide rejection of conventional hormone therapy (HT) after the initial publication
      of the Women's Health Initiative (WHI) led to unjustified use of custom
      compounded bioidentical hormones. In the USA, it became an unregulated drug
      manufacturer industry in disguise, without proper control and making false claims
      and misleading advertisements. Manufacturing quality is not ensured. Unspecific
      harm from compounding has occurred on a large scale, such as deaths from infected
      products and end-stage renal failure plus carcinoma due to confusion between
      different Chinese herbs. Oral estrogens increase venous thromboembolic and
      ischemic stroke events, even more when overdosed; these excess risks can be
      avoided by non-oral administration, readily accessible in custom-compounded HT by
      administering estradiol through diverse routes (of which transdermal is the best
      documented). Another risk specific to custom-compounded HT, resulting from
      estrogen/progestogen imbalance, might be excess endometrial carcinomas. HT can be
      optimized by continuously combining transdermal estradiol with progesterone (when
      required). Registered preparations do exist for such a more physiological
      treatment and therefore must be preferred. Custom compounding is only seldom
      legitimate, for example in case of allergy (such as to peanut oil) or to
      prescribe different combinations, doses or components (e.g. estriol,
      dehydroepiandrosterone or testosterone), even when not approved by local
      regulatory authorities despite being scientifically acceptable.

PMID- 28509625
TI  - Direct-Current Stimulation Does Little to Improve the Outcome of Working Memory
      Training in Older Adults.
AB  - The promise of transcranial direct-current stimulation (tDCS) as a modulator of
      cognition has appealed to researchers, media, and the general public. Researchers
      have suggested that tDCS may increase effects of cognitive training. In this
      study of 123 older adults, we examined the interactive effects of 20 sessions of
      anodal tDCS over the left prefrontal cortex (vs. sham tDCS) and simultaneous
      working memory training (vs. control training) on change in cognitive abilities.
      Stimulation did not modulate gains from pre- to posttest on latent factors of
      either trained or untrained tasks in a statistically significant manner. A
      supporting meta-analysis ( n = 266), including younger as well as older
      individuals, showed that, when combined with training, tDCS was not much more
      effective than sham tDCS at changing working memory performance ( g = 0.07, 95%
      confidence interval, or CI = [-0.21, 0.34]) and global cognition performance ( g
      = -0.01, 95% CI = [-0.29, 0.26]) assessed in the absence of stimulation. These
      results question the general usefulness of current tDCS protocols for enhancing
      the effects of cognitive training on cognitive ability.

PMID- 28509627
TI  - Impact of risk-reducing salpingo-oophorectomy in premenopausal women.
AB  - OBJECTIVES: To describe implications of premenopausal risk-reducing salpingo
      oophorectomy (RRSO) on quality of life, endocrine symptoms, sexual function,
      osteoporosis, cardiovascular health, metabolic syndrome, cognitive impairment and
      safety of hormone replacement therapy. METHODS: We searched the following
      electronic databases: The Cochrane Library, EMBASE, PsycInfo, and MEDLINE. We
      selected controlled and uncontrolled trials of premenopausal women undergoing
      RRSO. Two authors independently assessed studies for inclusion. Reference lists
      of included reports were searched manually for additional studies. RESULTS:
      Surgical menopause leads to more menopausal complaints and sexual dysfunction
      than natural menopause. Overall quality of life is not affected by surgery. In
      the limited literature, there is no evidence that RRSO leads to more osteopenia
      in comparison with natural menopause at a young age. Cohort studies show a slight
      impaired cardiovascular health. Cognitive function decreases later in life in
      premenopausal oophorectomized women. Short-term hormone replacement therapy seems
      to decline postmenopausal complaints and does not seem to increase the risk for
      breast carcinoma in mutation carriers without a personal history of breast
      carcinoma. CONCLUSIONS: The conclusions of this systematic review are limited by
      the absence of randomized, controlled trials. There is growing evidence from
      observational studies that RRSO may impact negatively on all-cause non-survival
      endpoints.

PMID- 28509628
TI  - Impact of the Village Model: Results of a National Survey.
AB  - Villages are a relatively new, consumer-directed model that brings together older
      adults in a community who have a mutual interest in aging in place. These
      membership organizations provide social and civic engagement opportunities,
      volunteer provided support services, and referral to vetted community providers
      to achieve their primary goals of promoting independence and preventing undesired
      relocations. This cross sectional survey of 1,753 active Village members from 28
      Villages across the US measured members' perceived impacts in the areas of social
      connection, civic engagement, service access, health and well-being, and ability
      to age in place. Results showed that involvement in the Village was a key factor
      associated with greater perceived impacts. Over half of members perceive that the
      Village has improved their sense of connection to others and their feeling that
      they have someone to count on. Though younger members in better health were more
      likely to perceive impacts in social connections, results suggest older women,
      living alone with some disability may be the most likely to experience improved
      health, quality of life, and mobility. The implications for social work practice
      are discussed.

PMID- 28509629
TI  - Nanoparticle-based delivery enhances anti-inflammatory effect of low molecular
      weight heparin in experimental ulcerative colitis.
AB  - Epithelial administration of low molecular weight heparin (LMWH) has proven its
      therapeutic efficiency in ulcerative colitis (UC) but still lacks of a
      sufficiently selective drug delivery system. Polymeric nanoparticles were used
      here not only to protect LMWH from intestinal degradation but also to provide
      targeted delivery to inflamed tissue in experimental colitis mice. LMWH was
      associated with polymethacrylate nanoparticles (NP) type A (PEMT-A) or type B
      (PEMT-B) of a size: 150 nm resulting in a maximum drug loading: 0.1 mg/mg. In a
      lipopolysaccharide-stimulated macrophages both, free LMWH and LMWH-NP have
      significantly reduced the cytokines secretion independently from cellular uptake.
      The in-vivo therapeutic efficiency was dose dependent as at low doses (100 IU/kg)
      only minor differences between free LMWH and LMWH-NP were found and the
      superiority of LMWH-NP became prominent with dose increase (500 IU/kg).
      Administration of LMWH-NP at 500 IU/kg has markedly improved the clinical
      activity as compared to LMWH while similarly pathophysiological indicators
      revealed increased therapeutic outcome in presence of NP compared to LMWH alone:
      Myeloperoxidase (Colitis control: 10 480 +/- 5335, LMWH-PEMT-A NP: 1507 +/- 2165,
      LMWH-PEMT-B NP: 382 +/- 143, LMWH: 8549 +/- 5021 units/g) and tumor necrosis
      factor: (Colitis control: 1636 +/- 544, LMWH-PEMT-A NP: 511 +/- 506, LMWH-PEMT-B
      NP: 435 +/- 473, LMWH: 1110 +/- 309 pg/g). Associating LMWH with NP is improving
      the anti-inflammatory efficiency of LMWH in-vivo by its protection against
      degradation in luminal environment and selective drug delivery. Such a
      combination holds promise for a highly specific therapy by its double selectivity
      towards the inflamed intestinal tissue. LMWH-PEMT NP have significantly improved
      the clinical activity in-vivo in comparison to free LMWH.

PMID- 28509630
TI  - MRD in AML: a role for detecting leukemic blasts at day 14 post-induction
      chemotherapy?

PMID- 28509632
TI  - Diagnostic Imaging in Veterinary Dental Practice.

PMID- 28509633
TI  - E-mental health and the veterinary profession.

PMID- 28509634
TI  - Vitamin D metabolism in canine and feline medicine.

PMID- 28509631
TI  - Improving balance, mobility, and dual-task performance in an adolescent with
      cerebral palsy: A case report.
AB  - BACKGROUND AND PURPOSE: Improving functional mobility is often a desired outcome
      for adolescents with cerebral palsy (CP). Traditional neurorehabilitation
      approaches are frequently directed at impairments; however, improvements may not
      be carried over into functional mobility. The purpose of this case report was to
      describe the examination, intervention, and outcomes of a task-oriented physical
      therapy intervention program to improve dynamic balance, functional mobility, and
      dual-task performance in an adolescent with CP. CASE DESCRIPTION: The participant
      was a 15-year-old girl with spastic triplegic CP (Gross Motor Classification
      System Level II). Examination procedures included the Canadian Occupational
      Performance Measure, 6-minute walk test, Muscle Power Sprint Test, 10 x 5-meter
      sprint test, Timed Up and Down Stairs Test, Gross Motor Function Measure,
      Gillette Functional Assessment Questionnaire, and functional lower extremity
      strength tests. Intervention focused on task-oriented dynamic balance and
      mobility tasks that incorporated coordination and speed demands as well as task
      specific lower extremity and trunk strengthening activities. Dual task demands
      were integrated into all intervention activities. OUTCOMES: Post-intervention
      testing revealed improvements in cardiovascular endurance, anaerobic power,
      agility, stair climbing, gross motor skills, and mobility. DISCUSSION: The
      participant appeared to benefit from a task-oriented program to improve dynamic
      balance, functional mobility, and dual-task performance.

PMID- 28509635
TI  - Disorders of performance-age bucking bulls.
AB  - OBJECTIVE To describe disorders of performance-age bucking bulls. DESIGN
      Retrospective case-control study. ANIMALS 78 bucking (cases) and 236 nonbucking
      (controls) beef bulls. PROCEDURES The medical record database of a referral
      hospital was reviewed to identify beef bulls > 1 year old that were examined for
      a medical or musculoskeletal disorder between January 1, 2000, and April 1, 2014.
      Bucking bulls were designated as cases, and nonbucking bulls were designated as
      controls. For each bull, the signalment, history, physical examination and
      diagnostic test results, and clinical diagnosis were recorded. The frequency of
      each disorder was compared between cases and controls. RESULTS Fifteen of 78
      (19%) cases and 132 of 236 (56%) controls had medical disorders; however, the
      frequency did not differ between the 2 groups for any medical disorder.
      Musculoskeletal disorders were identified in 55 (70.5%) cases and 109 (46%)
      controls. Cases were 10.55 times as likely as controls to have horn and sinus
      disorders. Of the 43 (55%) cases examined because of lameness, the thoracic limb
      was affected in 19 (44%). Compared with controls, cases were 13.37 and 3.31 times
      as likely to have a musculoskeletal disorder of the vertebral region and pelvic
      limb, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated bucking
      bulls were more likely than nonbucking bulls to develop horn and sinus disorders
      and musculoskeletal disorders of the vertebral region and pelvic limbs. The limb
      distribution of lameness for bucking bulls may differ from that for nonbucking
      bulls.

PMID- 28509636
TI  - Letters to the Editor.

PMID- 28509637
TI  - Anesthesia Case of the Month.

PMID- 28509638
TI  - What Is Your Neurologic Diagnosis?

PMID- 28509639
TI  - Factors associated with simulator-assessed laparoscopic surgical skills of
      veterinary students.
AB  - OBJECTIVE To determine whether simulator-assessed laparoscopic skills of
      veterinary students were associated with training level and prior experience
      performing nonlaparoscopic veterinary surgery and other activities requiring hand
      eye coordination and manual dexterity. DESIGN Experiment. SAMPLE 145 students
      without any prior laparoscopic surgical or fundamentals of laparoscopic surgery
      (FLS) simulator experience in years 1 (n = 39), 2 (34), 3 (39), and 4 (33) at a
      veterinary college. PROCEDURES A questionnaire was used to collect data from
      participants regarding experience performing veterinary surgery, playing video
      games, and participating in other activities. Participants performed a peg
      transfer, pattern cutting, and ligature loop-placement task on an FLS simulator,
      and FLS scores were assigned by an observer. Scores were compared among academic
      years, and correlations between amounts of veterinary surgical experience and FLS
      scores were assessed. A general linear model was used to identify predictors of
      FLS scores. RESULTS Participants were predominantly female (75%), right-hand
      dominant (92%), and between 20 and 29 years of age (98%). No significant
      differences were identified among academic years in FLS scores for individual
      tasks or total FLS score. Scores were not significantly associated with prior
      surgical or video game experience. Participants reporting no handicraft
      experience had significantly lower total FLS scores and FLS scores for task 2
      than did participants reporting a lot of handicraft experience. CONCLUSIONS AND
      CLINICAL RELEVANCE Prior veterinary surgical and video game experience had no
      influence on FLS scores in this group of veterinary students, suggesting that
      proficiency of veterinary students in FLS may require specific training.

PMID- 28509641
TI  - Seroprevalences of anti-Sarcocystis neurona and anti-Neospora hughesi antibodies
      among healthy equids in the United States.
AB  - OBJECTIVE To describe the general seroprevalence of anti-Sarcocystis neurona and
      anti-Neospora hughesi antibodies among healthy equids by use of indirect
      fluorescent antibody tests and determine potential risk factors for
      seropositivity. DESIGN Cross-sectional study. SAMPLE Whole blood samples
      collected from 5,250 equids (1 sample/animal) across 18 states in the United
      States during October 2013. PROCEDURES Information regarding potential risk
      factors (geographic region, breed, primary use, sex, and age) was collected along
      with the blood samples. For each equid, an indirect fluorescent antibody test was
      used to determine serum titers of antibody against each of the 2 protozoal
      parasites. Mixed-effects logistic regression models were created to determine ORs
      for seropositivity. RESULTS The overall seroprevalence of anti-S neurona and anti
      N hughesi antibodies in the tested equids was 78% and 34%, respectively. Of the
      equids, 31% were seropositive and 18% were seronegative for antibodies against
      both parasites. Factors associated with equids being seropositive for anti-S
      neurona antibodies were residence in the South, warmblood breed, and age > 5
      years. Seroprevalence of anti-N hughesi antibodies did not differ among equids in
      different states across the country, but warmblood breed and age > 5 years were
      associated with seropositivity. CONCLUSIONS AND CLINICAL RELEVANCE With regard to
      risk factors for S neurona and N hughesi exposure and antibody response among
      tested equids, older age was not unexpected; however, the influences of warmblood
      breed and geographic location on seropositivity for anti-S neurona antibody but
      not for anti-N hughesi antibody deserve further investigation.

PMID- 28509642
TI  - Pathology in Practice.

PMID- 28509643
TI  - ECG of the Month.

PMID- 28509644
TI  - Considerations for extralabel drug use in calves.

PMID- 28509645
TI  - What Is Your Diagnosis?

PMID- 28509646
TI  - Pathology in Practice.

PMID- 28509649
TI  - Advocating for veterinary medicine on the state level.

PMID- 28509648
TI  - Video-assisted extirpation of cranial mediastinal masses in dogs: 18 cases (2009
      2014).
AB  - OBJECTIVE To characterize clinical findings, surgical procedures, complications,
      and outcomes in dogs undergoing extirpation of masses from the cranial
      mediastinum via video-assisted thoracic surgery (VATS) and establish preliminary
      guidelines for case selection when considering VATS for thymectomy in dogs.
      DESIGN Retrospective case series. ANIMALS 18 client-owned dogs that underwent
      extirpation of a cranial mediastinal mass by means of VATS at 5 academic referral
      hospitals from 2009 through 2014. PROCEDURES Medical records were reviewed and
      data extracted regarding signalment, clinical signs, physical examination
      findings, diagnostic imaging results, surgical approach and duration, cytologic
      and histologic examination results, complications, outcome, and cause of death,
      when applicable. RESULTS 16 dogs had a thymoma, 1 had thymic anaplastic
      carcinoma, and 1 had hemangiosarcoma. Seven had both megaesophagus and myasthenia
      gravis. Median approximate tumor volume was 113.1 cm3 (interquartile range, 33.5
      to 313.3 cm3). Median duration of VATS was 117.5 minutes (interquartile range,
      91.5 to 136.3 minutes). Conversion to an open thoracic surgical procedure was
      required for 2 dogs, 1 of which died during surgery. Median survival time
      following VATS for dogs with thymoma and concurrent myasthenia gravis and
      megaesophagus was 20 days. Dogs with thymoma without paraneoplastic syndrome
      survived for >= 60 days, and none of these dogs died of disease-related causes.
      CONCLUSIONS AND CLINICAL RELEVANCE VATS appeared to be an acceptable approach for
      extirpation of masses from the cranial mediastinum in dogs under certain
      conditions. Dogs with myasthenia gravis and megaesophagus had a poor
      postoperative outcome.

PMID- 28509650
TI  - Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory
      drugs in horses.
AB  - Nonsteroidal anti-inflammatory drugs work through inhibition of cyclooxygenase
      (COX) and are highly effective for the treatment of pain and inflammation in
      horses. There are 2 clinically relevant isoforms of COX. Cyclooxygenase-1 is
      constitutively expressed and is considered important for a variety of physiologic
      functions, including gastrointestinal homeostasis. Thus, NSAIDs that selectively
      inhibit COX-2 while sparing COX-1 may be associated with a lower incidence of
      adverse gastrointestinal effects. Various formulations of firocoxib, a COX-2
      selective NSAID, labeled for use in horses are available in the United States.
      Equine practitioners should know that the FDA limits the use of firocoxib to
      formulations labeled for horses, regardless of price concerns. In addition,
      practitioners will benefit from understanding the nuances of firocoxib
      administration, including the importance of correct dosing and the
      contraindications of combining NSAIDs. Together with knowledge of the potential
      advantages of COX-2 selectivity, these considerations will help veterinarians
      select and treat patients that could benefit from this new class of NSAID.

PMID- 28509651
TI  - The concept of immunocompromised district might explain the carcinogenic
      progression in hidradenitis suppurativa.

PMID- 28509653
TI  - Redefined Boundaries: When Palliative Care Hits Home.

PMID- 28509652
TI  - Risk assessment of zinc oxide, a cosmetic ingredient used as a UV filter of
      sunscreens.
AB  - Zinc oxide (ZnO), an inorganic compound that appears as a white powder, is used
      frequently as an ingredient in sunscreens. The aim of this review was to examine
      the toxicology and risk assessment of ZnO based upon available published data.
      Recent studies on acute, sub-acute, and chronic toxicities of ZnO indicated that
      this compound is virtually non-toxic in animal models. However, it was reported
      that ZnO nanoparticles (NP) (particle size, 40 nm) induced significant changes in
      anemia-related hematologic parameters and mild to moderate pancreatitis in male
      and female Sprague-Dawley rats at 536.8 mg/kg/day in a 13-week oral toxicity
      study. ZnO displayed no carcinogenic potential, and skin penetration is low. No
      observed-adverse-effect level (NOAEL) ZnO was determined to be 268.4 mg/kg/day in
      a 13-week oral toxicity study, and a maximum systemic exposure dose (SED) of ZnO
      was estimated to be 0.6 mg/kg/day based on topical application of sunscreen
      containing ZnO. Subsequently, the lowest margin of safety (MOS) was estimated to
      be 448.2, which indicates that the use of ZnO in sunscreen is safe. A risk
      assessment was undertaken considering other routes of exposure (inhalation or
      oral) and major product types (cream, lotion, spray, and propellant). Human data
      revealed that MOS values (7.37 for skin exposure from cream and lotion type; 8.64
      for skin exposure of spray type; 12.87 for inhalation exposure of propellant
      type; 3.32 for oral exposure of sunscreen) are all within the safe range (MOS >
      1). Risk assessment of ZnO indicates that this compound may be used safely in
      cosmetic products within the current regulatory limits of 25% in Korea.

PMID- 28509654
TI  - Clinical reasoning-embodied meaning-making in physiotherapy.
AB  - This article examines physiotherapists' lived experience of practicing
      physiotherapy in primary care, focusing on clinical reasoning and decision-making
      in the case of a patient we call Eva. The material presented derives from a
      larger study involving two women participants, both with a protracted history of
      neck and shoulder pain. A total of eight sessions, all of them conducted by the
      first author, a professional physiotherapist, in his own practice room, were
      videotaped, after which the first author transcribed the sessions and added
      reflective notes. One session emerged as particularly stressful for both parties
      and is explored in detail in this article. In our analysis, we seek to be
      attentive to the experiences of physiotherapy displayed and to explore their
      meaning, significance and uniqueness from a phenomenological perspective. Our
      research reveals the complexity of integrating multiple theoretical perspectives
      of practice in clinical decision-making and suggests that a phenomenological
      perspective can provide insights into clinical encounters through its recognition
      of embodied knowledge. We argue that good physiotherapy practice demands
      tactfulness, sensitivity, and the desire to build a cooperative patient-therapist
      relationship. Informed by theoretical and practical knowledge from multiple
      disciplines, patient management can evolve and unfold beyond rehearsed routines
      and theoretical principles.

PMID- 28509655
TI  - Letter from the editor.

PMID- 28509656
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 28509657
TI  - The Palliative Care Challenge: Analysis of Barriers and Opportunities to
      Integrate Palliative Care in Europe in the View of National Associations.
AB  - BACKGROUND: Palliative care (PC) development is diverse and lacks an effective
      integration into European healthcare systems. This article investigates levels of
      integrated PC in European countries. METHODS: A qualitative survey was undertaken
      for the 2013 EAPC Atlas of PC in Europe with boards of national associations,
      eliciting opinions on opportunities for, and barriers to, PC development.
      ANALYSIS: Barriers and opportunities directly related to PC integration were
      identified and analyzed thematically according (1) to the dimensions of the World
      Health Organization (WHO) public health model and (2) by the degree of service
      provision in each country. A frequency analysis of dimensions and level of
      provision was also conducted. RESULTS: In total, 48/53 (91%) European countries
      responded to the survey. A total of 43 barriers and 65 opportunities were
      identified as being related to PC integration. Main barriers were (1) lack of
      basic PC training, with a particular emphasis on the absence of teaching at the
      undergraduate level; (2) lack of official certification for professionals; (3)
      lack of coordination and continuity of care for users and providers; (4) lack of
      PC integration for noncancer patients; (5) absence of PC from countries'
      regulatory frameworks; and (6) unequal laws or regulations pertaining to PC
      within countries. Innovations in education and new regulatory frameworks were
      identified as main opportunities in some European countries, in addition to
      opportunities around the implementation of PC in home care, nursing home
      settings, and the earlier integration of PC into patients' continuum of care.
      With increasing provision of services, more challenges for the integration are
      detected (p < 0.005). CONCLUSION: A set of barriers and opportunities to PC
      integration has been identified across Europe, by national associations, offering
      a barometer against which to check the challenge of integration across countries.

PMID- 28509658
TI  - Haemosporidian Parasites of Reptiles and Birds from Gabon, Central Africa.
AB  - Haemosporidian parasites are protozoans that infect many different vertebrate
      hosts. Re-examination of the diversity of haemosporidian parasites, using
      molecular tools, has generally led to rearrangements of traditional
      classifications. In this study, we explored the diversity of haemosporidian
      parasites infecting some species of reptile and birds living in the forests of
      Gabon, Central Africa, by analyzing a collection of 128 samples of reptiles and
      birds. We found that samples from 2 tortoise species (Pelusios castaneus and
      Kinixys erosa) and 3 bird species (Turtur afer, Ceratogymna atrata, and Agelastes
      niger) were infected by Haemocystidium spp. and Parahaemoproteus spp.,
      respectively. From an ecological point of view, these lineages of parasites do
      not show host specificity because we have found them in several host species (2
      tortoise and 3 bird species) that come from different areas of Gabon forest which
      are infected with these parasites. Also, our phylogenetic analyses revealed that
      the obtained lineages are related to isolates from other continents found in the
      same groups of vertebrates. Thus, our results show that haemosporidian parasites
      are also infecting central African vertebrates and that new lineages of these
      parasites are circulating in wild animals of the Gabon forest.

PMID- 28509659
TI  - Reasons for transferring HIV care in London.
AB  - People living with HIV in England, as well as non-UK born and individuals without
      residency, can access free HIV care at any service in England. We investigated
      reasons for transfer of care to three London HIV units by asking all patients
      transferring to fill in a questionnaire exploring reasons for leaving their
      previous centre and reasons for choosing the new service. A total of 111 patients
      completed the questionnaire. The majority of patients transferred from abroad to
      London HIV units, compared to within the UK. The main reason for leaving their
      current service was location, which was also the main reason for choosing the
      service they transferred to. The results of this audit can be used to improve all
      services to ensure any concerns patients may have are eliminated and provide
      healthcare tailored to patients' needs.

PMID- 28509661
TI  - The relationship between interpersonal trauma history and the functions of non
      suicidal self-injury in young adults: An experience sampling study.
AB  - Non-suicidal self-injury (NSSI) has been reported to serve a range of functions
      for individuals who engage in it. Despite considerable variation in NSSI
      functions between individuals, limited attention has been paid to exploring
      relationships between NSSI functions and other characteristics of self-injuring
      individuals, such as trauma history. This is despite allusion to trauma history
      in the suggested etiology of some NSSI functions (e.g., anti-dissociation, self
      punishment). The present study used a 21-day online daily diary to explore
      possible relationships between common NSSI functions and past interpersonal
      trauma in community young adults (n = 38). The interpersonal boundaries and anti
      dissociation functions significantly related to interpersonal trauma severity in
      multiple regression analyses; the interpersonal boundaries function continued to
      significantly relate to interpersonal trauma severity when controlling for the
      number of NSSI functions endorsed.

PMID- 28509663
TI  - Editorial issue 2/2017International journal of psychiatry in clinical practice.

PMID- 28509664
TI  - Reliability of the Dissociative Trance Disorder Interview Schedule: A preliminary
      report.
AB  - One hundred inpatients in a hospital-based Trauma Program in the USA were
      interviewed with the Dissociative Trance Disorder Interview Schedule (DTDIS).
      There were no significant differences for the DTDIS total score or any of the
      subscale scores on test-retest: all t-values comparing the two administrations of
      the DTDIS were below 0.7, and all p-values were above 0.5. Cronbach's alpha for
      the US sample was 0.966 and for the Israeli sample it was 0.971. The findings
      indicate that the DTDIS has good reliability and may be suitable for use in cross
      cultural research; however, the results require replication by independent
      researchers in a variety of cultures and languages, and in both clinical and
      nonclinical samples.

PMID- 28509665
TI  - Evaluation of diet pattern and weight gain in postmenopausal women enrolled in
      the Women's Health Initiative Observational Study.
AB  - It is unclear which of four popular contemporary diet patterns is best for weight
      maintenance among postmenopausal women. Four dietary patterns were characterised
      among postmenopausal women aged 49-81 years (mean 63.6 (sd 7.4) years) from the
      Women's Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced
      carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet
      consistent with the US Department of Agriculture's Dietary Guidelines for
      Americans (DGA). Discrete-time hazards models were used to compare the risk of
      weight gain (>=10 %) among high adherers of each diet pattern. In adjusted
      models, the reduced-carbohydrate diet was inversely related to weight gain (OR
      0.71; 95 % CI 0.66, 0.76), whereas the low-fat (OR 1.43; 95 % CI 1.33, 1.54) and
      DGA (OR 1.24; 95 % CI 1.15, 1.33) diets were associated with increased risk of
      weight gain. By baseline weight status, the reduced-carbohydrate diet was
      inversely related to weight gain among women who were normal weight (OR 0.72; 95
      % CI 0.63, 0.81), overweight (OR 0.67; 95 % CI 0.59, 0.76) or obese class I (OR
      0.63; 95 % CI 0.53, 0.76) at baseline. The low-fat diet was associated with
      increased risk of weight gain in women who were normal weight (OR 1.28; 95 % CI
      1.13, 1.46), overweight (OR 1.60; 95 % CI 1.40, 1.83), obese class I (OR 1.73; 95
      % CI 1.43, 2.09) or obese class II (OR 1.44; 95 % CI 1.08, 1.92) at baseline.
      These findings suggest that a low-fat diet may promote weight gain, whereas a
      reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.

PMID- 28509668
TI  - Norepinephrine in septic shock: when and how much?
AB  - PURPOSE OF REVIEW: Norepinephrine is the first-line agent recommended during
      resuscitation of septic shock to correct hypotension due to depressed vascular
      tone. Important clinical issues are the best timing to start norepinephrine, the
      optimal blood pressure target, and the best therapeutic options to face
      refractory hypotension when high doses of norepinephrine are required to reach
      the target. RECENT FINDINGS: Recent literature has reported benefits of early
      administration of norepinephrine because of the following reasons: profound and
      durable hypotension is an independent factor of increased mortality, early
      administration of norepinephrine increases cardiac output, improves
      microcirculation and avoids fluid overload. Recent data are in favor of targeting
      a mean arterial pressure of at least 65 mmHg and higher values in case of chronic
      hypertension. When hypotension is refractory to norepinephrine, it is recommended
      adding vasopressin, which is relatively deficient during sepsis and acts on other
      vascular receptors than alpha1-adernergic receptors. However, increasing the dose
      of norepinephrine further cannot be discouraged. SUMMARY: Early administration of
      norepinephrine is beneficial for septic shock patients to restore organ
      perfusion. The mean arterial pressure target should be individualized. Adding
      vasopressin is recommended in case of shock refractory to norepinephrine.

PMID- 28509667
TI  - Evaluation of hippocampal infolding angle and incomplete hippocampal inversion in
      pediatric patients with epilepsy and febrile seizures.
AB  - PURPOSE: We aimed to investigate the frequency of incomplete hippocampal
      inversion (IHI) and the hippocampal infolding angle (HIA) in pediatric patients
      with no additional abnormal findings in the brain. METHODS: Pediatric brain
      magnetic resonance imaging (MRI) examinations conducted between September 2012
      and February 2015 were screened and 83 patients with epilepsy, 49 patients with
      febrile convulsion, and 74 control patients were included in this retrospective
      study. Presence of IHI was evaluated and HIA was measured on MRI. RESULTS: IHI
      was found in 23 patients in the epilepsy group (27.7%), 15 patients in the
      febrile convulsion group (30.6%), and 14 patients in the control group (19.0%),
      with no significant difference between the groups (P = 0.27). Compared with the
      epilepsy and febrile convulsion groups, HIA was significantly larger in the
      control group in sections of the right cerebral pedincule, the left cerebral
      pedincule, and the right superior cerebellar pedincule. No correlation was found
      between the laterality of the epileptogenic focus in the epilepsy group and
      existence of IHI, nor between age and HIA values among the groups. CONCLUSION:
      Although IHI is not an uncommon abnormality in the normal pediatric population,
      decreased HIA is more frequently found in patients with epilepsy or febrile
      convulsions.

PMID- 28509669
TI  - Genetic advances in systemic lupus erythematosus: an update.
AB  - PURPOSE OF REVIEW: More than 80 susceptibility loci are now reported to show
      robust genetic association with systemic lupus erythematosus (SLE). The
      differential functional effects of the risk alleles for the majority of these
      loci remain to be defined. Here, we review current SLE association findings and
      the recent progress in the annotation of noncoding regions of the human genome as
      well as the new technologies and statistical methods that can be applied to
      further the understanding of SLE genetics. RECENT FINDINGS: Genome-wide
      association studies (GWAS) have markedly expanded the catalogue of genetic
      signals contributing to SLE development; we can now explain more than 50% of the
      disease's heritability. Expression quantitative trait loci mapping with
      colocalization analysis of GWAS results help to identify the underlying causal
      genes. The Encyclopedia of DNA elements, Roadmap Epigenome, and the Blueprint
      Epigenome projects have jointly annotated more than 80% of the noncoding genome,
      providing a wealth of information (from healthy individuals) to define the
      functional elements within the risk loci. Technologies, such as next-generation
      sequencing, chromatin structure determination, and genome editing, will help
      elucidate the actual mechanisms that underpin SLE risk alleles. SUMMARY: Gene
      expression and epigenetic databases provide a valuable resource to interpret
      genetic association in SLE. Expansion of such resources to include disease status
      and multiple ancestries will further aid the exploration of the biology
      underlying the genetics.

PMID- 28509666
TI  - An inhibitory gate for state transition in cortex.
AB  - Large scale transitions between active (up) and silent (down) states during quiet
      wakefulness or NREM sleep regulate fundamental cortical functions and are known
      to involve both excitatory and inhibitory cells. However, if and how inhibition
      regulates these activity transitions is unclear. Using fluorescence-targeted
      electrophysiological recording and cell-specific optogenetic manipulation in both
      anesthetized and non-anesthetized mice, we found that two major classes of
      interneurons, the parvalbumin and the somatostatin positive cells, tightly
      control both up-to-down and down-to-up state transitions. Inhibitory regulation
      of state transition was observed under both natural and optogenetically-evoked
      conditions. Moreover, perturbative optogenetic experiments revealed that the
      inhibitory control of state transition was interneuron-type specific. Finally,
      local manipulation of small ensembles of interneurons affected cortical
      populations millimetres away from the modulated region. Together, these results
      demonstrate that inhibition potently gates transitions between cortical activity
      states, and reveal the cellular mechanisms by which local inhibitory
      microcircuits regulate state transitions at the mesoscale.

PMID- 28509670
TI  - Pediatric nasal surgery: timing and technique.
AB  - PURPOSE OF REVIEW: Timing of pediatric nasal surgery has always been a
      controversial topic. Concern over disrupting growing parts of the face and
      causing permanent facial deformity has led to a primarily conservative approach.
      Many surgeons feel that it is prudent to wait until the patient has completed
      nasal growth after puberty to pursue nasal surgery. RECENT FINDINGS: Recently,
      this attitude has been challenged with evidence that not only is nasal surgery in
      the pediatric age group not a detriment to facial growth, but failure to correct
      significant nasal deformity may actually cause dysmorphic facial growth secondary
      to obligate mouth breathing. Because of this, recent studies have focused on
      determining safe surgical techniques for pediatric nasal surgery, including
      inferior turbinate reduction, septoplasty and rhinoplasty. Research focus on this
      topic has also been expanded to include quality-of-life measures after nasal
      surgery. SUMMARY: Pediatric nasal surgery prior to puberty is not only safe, but
      may prevent facial deformity in certain patients.

PMID- 28509671
TI  - Complications in facial Mohs defect reconstruction.
AB  - PURPOSE OF REVIEW: To review the recent literature in regards to complications
      after reconstruction of Mohs defects, outline common pitfalls and to discuss the
      literature on avoiding complications as outlined per aesthetic subunit. RECENT
      FINDINGS: Complications in facial Mohs reconstruction commonly consist of
      infection, wound necrosis and dehiscence, hematoma and suboptimal scarring.
      However, site-specific complications such as hairline or eyebrow distortion,
      eyelid retraction or ectropion, nasal contour abnormality, alar retraction, nasal
      valve compromise, significant facial asymmetry or even oral incompetence must
      also be considered. SUMMARY: A successful reconstruction mimics the premorbid
      state and maintains function. The use of perioperative antibiotics, sterile
      technique, meticulous hemostasis, subcutaneous dissection and deep sutures to
      minimize wound tension should be considered for all Mohs reconstructions.
      Cartilage grafting can minimize nasal deformity and obstruction. Reconstruction
      near the lower eyelid should employ periosteal suspension sutures to minimize
      downward tension and lid retraction. Perioral complications, such as microstomia
      and oral incompetence, typically improve with time and therapy. Always consider
      secondary procedures such as dermabrasion, steroid injection, scar revision and
      laser resurfacing to help optimize aesthetic outcome.

PMID- 28509672
TI  - Update on injectables in the nose.
AB  - PURPOSE OF REVIEW: The use of injectable fillers for nonsurgical rhinoplasty has
      increased tremendously over the past decade. This review describes the most
      commonly used fillers and their indications in the context of recent reports of
      both their successes and failures. RECENT FINDINGS: Hyaluronic acid and calcium
      hydroxylapatite are the two most commonly used fillers for injection. Recent
      studies have found that most injectable fillers are met with success and patient
      satisfaction, but vascular complications are still a serious problem of which
      physicians should be wary. SUMMARY: Injectable fillers should continue to be
      considered for patients on a case-by-case basis, but physicians should be
      knowledgeable of the various filler types, their indications, and injection
      technique to prevent serious complications.

PMID- 28509674
TI  - Evidence for more intensive cholesterol lowering.
AB  - PURPOSE OF REVIEW: In randomized clinical trials, reduction in cardiovascular
      disease (CVD) risk with cholesterol-lowering drugs correlates with the LDL
      cholesterol decrease. However, because the majority have investigated a fixed
      statin dose, current guidelines disagree about the use of statin dose titration
      or non-statin adjunctive cholesterol-lowering drugs. RECENT FINDINGS: We
      conducted a meta-analysis of all randomized controlled trials with CVD end
      points, comparing two intensities of lipid-lowering regimens within the same
      population, using varying statins doses and/or potency, ezetimibe or PCSK9
      inhibitors and compared the observed number of patients needed to be treated for
      10 years to prevent one CVD event (NNT) with NNT predicted from trials of
      predominantly single-dose statin.Some 75439 participants in 10 randomized studies
      were included. The mean 10-year CVD risk in controls was around 50% and the
      incremental mean LDL cholesterol decrease 0.95 mmol/l (36.7 mg/dl). Observed NNT
      closely correlated with those predicted from predominantly single-dose statin
      trials [18.2 and 17.1; Pearson R=0.844 (P=0.001)]. When pre-treatment LDL
      cholesterol exceeded 4 mmol/l (155 mg/dl), achieving a target LDL cholesterol of
      1.8 mmol/l (70 mg/dl) was the most effective strategy. At lower pre-treatment
      levels, fixed-dose statin equivalent to atorvastatin 80 mg daily was superior.
      The target of 40% reduction in non-high density lipoprotein cholesterol was least
      effective regardless of pre-treatment LDL cholesterol. SUMMARY: We conclude that
      when initial LDL cholesterol exceeds 4 mmol/l and absolute CVD risk demands it, a
      target value of 1.8 mmol/l should be achieved, if necessary by adding ezetimibe
      and/or PCSK9 inhibitors to statin treatment.

PMID- 28509675
TI  - Acute and Long-Term Effects of LVAD Support on Right Ventricular Function in
      Children with Pediatric Pulsatile Ventricular Assist Devices.
AB  - Right ventricular failure (RVF) is a significant issue when considering left
      ventricular assist device (LVAD) implantation in pediatrics. The aim of this
      study was to evaluate the effects of LVAD on right ventricular (RV) function in
      children. We retrospectively reviewed clinical and echocardiographic data of
      children who underwent Berlin Heart EXCOR LVAD focusing on RV function before and
      after implantation (1, 3, and 6 month follow-up). An isolated LVAD was used in 27
      patients. Median age was 11 months (interquartile range [IQR]: 5-24 months), with
      a median weight of 6.3 kg (IQR: 5-9 kg). Median time on ventricular assist device
      (VAD) support was 147 days (IQR: 86-210 days). Twenty patients were successfully
      bridged to orthotopic heart transplantation (OHT) (74%), six patients died (22%),
      and also heart function recovered in one patient (4%). Before LVAD implantation,
      nine patients (33%) showed a RV fractional area change (RVFAC) less than or equal
      to 30%. After implantation, mean RVFAC increased up until the 3 month follow-up
      (43.13%; p = 0.033) and then slightly decreased. In a subgroup of 18 patients,
      the average strain value increased after the 1 month follow-up (p = 0.022). Right
      ventricular failure developed in 33% of patients before the 1 month follow-up,
      and 7.4% experienced RVF at the 6 month follow-up. No patient required
      biventricular assist device (BiVAD). In our population, pulsatile-flow LVAD in
      children allows optimal RV decompression and function post-LVAD as measured by
      improvement in RV function at echo particularly at 1 and 3 month follow-up. At
      long-term follow-up, the beneficial effects of LVAD on RV function seem to be
      reduced as signs and symptoms of late RVF may develop in some patients despite
      LVAD support.

PMID- 28509673
TI  - Immune responses to invasive aspergillosis: new understanding and therapeutic
      opportunities.
AB  - PURPOSE OF REVIEW: Invasive aspergillosis is a worldwide disease that primarily
      affects immune-compromised patients, agricultural workers with corneal abrasions,
      individuals with structural lung disease, and patients with primary immune
      deficiency. The critical function of the immune system is to prevent the
      germination of airborne conidia into tissue-invasive hyphae. This review covers
      recent advances that shape our understanding of anti-Aspergillus immunity at the
      molecular and cellular level. RECENT FINDINGS: Host defense against conidia and
      hyphae occurs via distinct molecular mechanisms that involve intracellular and
      extracellular killing pathways, as well as cooperation between different myeloid
      cell subsets. The strength and efficacy of the host response is shaped by the
      tissue microenvironment. In preclinical models of disease, host immune
      augmentation strategies have yielded benefits, yet translating these insights
      into therapeutic strategies in humans remains challenging. SUMMARY: Although
      advances in early diagnostic strategies and in antifungal drugs have ameliorated
      clinical outcomes of invasive aspergillosis, further improvements depend on
      gaining deeper insight into and translating advances in anti-Aspergillus
      immunity.

PMID- 28509676
TI  - Isolated Right Ventricular Mechanical Support: Outcomes and Prognosis.
AB  - Right ventricular (RV) failure that necessitates isolated mechanical support is
      extremely rare. Outcomes have not been described and are limited to case reports.
      We sought to evaluate this select group of patients and determine their 30 day
      and 1 year survival. We retrospectively reviewed the Mechanical Assist Device
      Database at Columbia University from 2007 to 2015. Inclusion criteria consisted
      of patients who received isolated RV assist devices (RVADs) without mechanical
      support of the left ventricle. We evaluated survival, duration of support,
      intensive care unit (ICU) length of stay, and adverse events. There were 55
      patients who underwent RVAD placement between February 2007 and April 2015.
      Eleven of these patients received isolated RVADs in the absence of mechanical
      circulatory support of the left ventricle. Average duration of support was 13.6
      days with a median duration of 12 days. Thirty day and 1 year survival was 72.7%
      and 54.6%, respectively. This case series is the first to describe 30 day and 1
      year outcomes for patients with isolated RV mechanical support. We propose an
      interdisciplinary institutional algorithm based on our study population that
      maximizes medical therapy and then pursues invasive forms of mechanical support
      when end-organ damage persists.

PMID- 28509677
TI  - Short article: Stool cytomegalovirus polymerase chain reaction for the diagnosis
      of cytomegalovirus-related gastrointestinal disease.
AB  - OBJECTIVES: The diagnosis of cytomegalovirus-related gastrointestinal disease
      (CMV-GI disease) still requires histopathology, but biopsy is considered
      invasive. Stool CMV PCR has been reported in adults as an alternative method to
      diagnose this condition; hence, the results between studies are discrepant.
      Moreover, no pediatric studies on stool CMV real-time PCR in CMV-GI disease have
      been carried out. Here, we evaluate the value of stool CMV real-time PCR in
      detecting CMV-GI disease among immunocompromised children. METHODS: We enrolled
      immunocompromised patients aged younger than 20 years who presented with
      gastrointestinal symptoms at a teaching hospital during January 2015-March 2016.
      Stool samples were analyzed for CMV real-time PCR. All patients underwent
      esophagogastroduodenoscopy and colonoscopy with mucosal biopsy. RESULTS: We
      performed stool CMV real-time PCR in 31 patients, but two could not undergo
      endoscopy. Therefore, 29 patients were analyzed. Two additional stool samples
      showed inhibitors that interfere with the PCR testing and were precluded from the
      final analysis. Among 27 patients, we found CMV-GI disease in seven (26%)
      patients. The sensitivity, specificity, and accuracy of stool CMV real-time PCR
      were 71, 85, and 82%, respectively. We also found that all patients with CMV-GI
      disease had positive plasma CMV real-time PCR (>150 copies/ml). A significant
      association between stool and plasma CMV real-time PCR was also noted (P<0.001).
      CONCLUSION: Stool CMV real-time PCR may be used as a noninvasive tool in the
      diagnosis of CMV-GI disease. Plasma CMV real-time PCR shows a significant
      correlation with stool CMV real-time PCR and also represents high diagnostic
      values.

PMID- 28509678
TI  - Becoming a chef in the human leukocyte antigen kitchen: interpretation and
      modification of human leukocyte antigen-antibody assays.
AB  - PURPOSE OF REVIEW: Fluorescence-based human leukocyte antigen (HLA) antibody
      detection methods, including flow cytometric crossmatch and single antigen bead
      assays revolutionized HLA antibody identification and assessment of immunological
      risk in transplant candidates and patients. Nevertheless, these assays are not
      flawless and their interpretation can be complex. This review highlights the
      limitations of the single antigen bead and flow cytometric crossmatch assays and
      discusses protocol modifications and interpretive approaches to address these
      issues. RECENT FINDINGS: Several limitations of HLA antibody detection methods
      have been identified in recent years. Protocol variability, denatured epitopes,
      and interfering factors can all significantly impact the identification of
      clinically relevant HLA antibodies. A number of solutions to address these
      challenges have been developed. These include pretreatment of sera, method
      standardization, and protocol modifications. In addition, HLA epitope-based
      analysis approaches to improve interpretation of antibody test results have been
      introduced. SUMMARY: In the 50 years, since Patel and Terasaki first developed
      the crossmatch assay there have been remarkable advances in HLA antibody testing
      methodology. However, with these advances, new problems emerged and solutions had
      to be developed. As the technology continues to evolve, our methods and ability
      to interpret results must keep pace to provide transplant patients with the best
      possible care.

PMID- 28509679
TI  - The impact of next-generation sequencing in immunogenetics: current status and
      future directions.
AB  - PURPOSE OF REVIEW: Next-generation sequencing (NGS) has now been established, and
      widely recognized, to be the preferred choice for human leukocyte antigen (HLA)
      typing. This transformation is based upon the many scientific, operational and
      economic benefits this technology affords. In this report, we review the major
      advantages, existing limitations and significant promise derived from adopting
      this technology in immunogenetics. RECENT FINDINGS: Significant benefits have
      emerged from the usage of NGS in a relatively short period, whereby we realize
      that this technology not only helps addressing the technical and operational
      problems we have had with the legacy methods for HLA typing, but equally
      important, it also allows for creative applications in stem cell and organ
      transplantation, new ways to investigate associations of the major
      histocompatibility complex (MHC) with many diseases and enhance our understanding
      regarding the MHC and non-MHC genomic interactions. The emerging picture is one
      of significant benefits in the diagnostic sphere of immunogenetics and
      transplantation and one of interconnectivity, integrating the many biological
      pathways controlled and affected by this unique genomic region. SUMMARY: NGS has
      revolutionized the science and practice of immunogenetics. In this article, we
      identify the still unresolved issues, the current benefits to transplantation and
      the potential for dissecting the complexity of the MHC, one of the most
      fascinating regions of the human genome. Using current trends, an attempt is made
      to predict future directions and outcomes.

PMID- 28509680
TI  - Analyzing Dental Implant Sites From Cone Beam Computed Tomography Scans on a
      Tablet Computer: A Comparative Study Between iPad and 3 Display Systems.
AB  - PURPOSE: The aim of this study was to compare a medical-grade PACS (picture
      archiving and communication system) monitor, a consumer-grade monitor, a laptop
      computer, and a tablet computer for linear measurements of height and width for
      specific implant sites in the posterior maxilla and mandible, along with
      visualization of the associated anatomical structures. MATERIAL AND METHODS: Cone
      beam computed tomography (CBCT) scans were evaluated. The images were reviewed
      using PACS-LCD monitor, consumer-grade LCD monitor using CB-Works software, a 13"
      MacBook Pro, and an iPad 4 using OsiriX DICOM reader software. The operators had
      to identify anatomical structures in each display using a 2-point scale. User
      experience between PACS and iPad was also evaluated by means of a questionnaire.
      RESULTS: The measurements were very similar for each device. P-values were all
      greater than 0.05, indicating no significant difference between the monitors for
      each measurement. The intraoperator reliability was very high. The user
      experience was similar in each category with the most significant difference
      regarding the portability where the PACS display received the lowest score and
      the iPad received the highest score. CONCLUSIONS: The iPad with retina display
      was comparable with the medical-grade monitor, producing similar measurements and
      image visualization, and thus providing an inexpensive, portable, and reliable
      screen to analyze CBCT images in the operating room during the implant surgery.

PMID- 28509681
TI  - Neuroimaging as a tool to study the sources of phenotypic heterogeneity in
      Huntington's disease.
AB  - PURPOSE OF REVIEW: Huntington's disease is a neurodegenerative disorder
      characterized by a triad of motor, cognitive and psychiatric disturbances. There
      is great variability regarding the prominence and evolution of each type of
      clinical sign. One possible source of phenotypic heterogeneity could be the more
      prominent degeneration of specific brain circuits. The scope of this review is to
      highlight the most recent neuroimaging studies that have analysed the
      relationship between brain changes and motor, cognitive and psychiatric
      alterations in Huntington's disease. RECENT FINDINGS: The results from recent
      neuroimaging studies are heterogeneous. Although there is a great overlap between
      the different regions associated with each symptomatic domain, there is some
      degree of differentiation. For example, the motor network is associated with
      motor impairment, whereas the ventral striatum is especially involved in
      emotional deficits related with psychiatric problems. SUMMARY: Motor, cognitive
      and psychiatric impairments are associated with structural and functional brain
      biomarkers. However, the specificity of the regions involved remains unknown,
      because these studies focused on specific regions and symptoms. In order to tease
      apart the neural substrates that underlie the phenotypic heterogeneity in
      Huntington's disease, multivariate approaches combining brain and behavioural
      measures related to all symptomatic domains should be considered in the future.

PMID- 28509682
TI  - New neurosurgical approaches for tremor and Parkinson's disease.
AB  - PURPOSE OF REVIEW: The objective of this review is to gather the newest advances
      in the surgical treatment of tremor and Parkinson's disease. We will briefly
      discuss the potential applications of the new technologies of deep brain
      stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS).
      RECENT FINDINGS: Novel DBS devices are being progressively adopted, particularly
      electrodes allowing a longer stimulating surface (suitable for multiple targets
      stimulation) and current radial steering (to minimize side effects of
      stimulation). New implantable pulse generators are also able to record neurons
      and are generating enough knowledge to advance the implementation of adaptive
      (closed-loop) DBS.Over the last years, 'minimally-invasive' neurosurgical
      approaches for the treatment of movement disorders have been developed: gamma
      knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have
      shown the benefits of MRgFUS targeting the thalamus and pallidus for the
      treatment of tremor and Parkinson's disease. SUMMARY: The initial clinical data
      are certainly promising and have expanded the current portfolio of neurosurgical
      treatments of movement disorders. Many issues are yet to be addressed,
      particularly safety of MRgFUS-and how these new treatments compare with the
      existing ones.

PMID- 28509683
TI  - Conjunctival Squamous Cell Neoplasia Associated With Ocular Cicatricial
      Pemphigoid.
AB  - The purpose of this study was to describe a possible causal relationship between
      ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two
      middle-aged female patients with already diagnosed OCP were studied in regard to
      the subsequent onset of conjunctival squamous neoplasia. Their clinical
      histories, ocular examinations, clinical photographs, and results of biopsies and
      any ancillary immunofluorescent laboratory evaluation studies were carefully
      reviewed. One patient had a preinvasive squamous dysplasia and the other an
      invasive squamous cell carcinoma, both in the unequivocal setting of OCP with
      bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients
      had been receiving intensive immunotherapy consisting of some combination of
      corticosteroids, rituximab, and interferon alpha. Both patients had a positive
      immunofluorescent study demonstrating immunoreactants at the level of the
      epithelial basement membrane. Each patient had 2 earlier negative
      immunofluorescent studies before a third was positive. While rare, there is 1
      previous report of an association between OCP and conjunctival squamous
      neoplasia. The current report provides more data supporting the proposal that
      this conjunction is more than a random event. Repeat immunofluorescent studies
      after an initial negative result in a patient with strong clinical signs of OCP
      are imperative due to the frequency of false negative studies in the context of
      clinically persuasive disease.

PMID- 28509684
TI  - Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy,
      Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma.
AB  - BACKGROUND: The release of damage-associated molecular pattern molecules in the
      extracellular space secondary to injury has been shown to cause systemic
      activation of the coagulation system and endothelial cell damage. We hypothesized
      that pediatric trauma patients with increased levels of histone-complexed DNA
      fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that
      would be associated with poor outcomes. METHODS: We conducted a prospective
      observational study of 149 pediatric trauma patients and 62 control patients at
      two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were
      collected upon arrival and at 24 h, analyzed for hcDNA, coagulation
      abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was
      assessed with impedance aggregometry (Multiplate) and coagulation parameters were
      assessed by measuring prothrombin time ratio in plasma and the use of
      viscoelastic techniques (Rotational Thromboelastometry) in whole blood. RESULTS:
      The median age was 8.3 years, the median injury severity score (ISS) was 20, and
      overall mortality was 10%. Significantly higher levels of hcDNA were found on
      admission in patients with severe injury (ISS > 25), coagulopathy, and/or
      abnormal platelet aggregation. Patients with high hcDNA levels also had
      significant elevations in plasma levels of syndecan-1, suggesting damage to the
      endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in
      non-survivors. CONCLUSION: hcDNA is released following injury and correlates with
      coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early
      after severe pediatric trauma. These results indicate that hcDNA may play an
      important role in development of coagulation abnormalities and endothelial
      glycocalyx damage in children following trauma.

PMID- 28509686
TI  - Accuracy of Point-of-Care Ultrasonography for Pediatric Ankle Sprain Injuries.
AB  - OBJECTIVES: In children with radiograph fracture-negative lateral ankle injuries,
      the main objective of this pilot study was to explore the accuracy, sensitivity,
      and specificity of point-of-care ultrasound (POCUS) performed by a pediatric
      emergency physician in diagnosing anterior talofibular ligament injuries,
      radiographically occult distal fibular fractures, and effusions compared with
      reference standard magnetic resonance imaging (MRI). METHODS: This was a
      prospective cohort pilot study. Children aged 5 to 17 years with an isolated,
      acute lateral ankle injury and fracture-negative ankle radiographs were eligible
      for enrolment. Within 1 week of the injury, enrolled children returned for MRI
      and POCUS of both ankles. RESULTS: Seven children were enrolled, with a mean age
      12.1 (SD, 3.0) years. Overall, POCUS agreed with MRI with respect to anterior
      talofibular ligament injury in 4 (57%) of 7 cases. Of the 2 cases with MRI
      confirmed ligament damage, POCUS accurately identified and graded the extent of
      ligament damage in 1 case. Point-of-care ultrasound falsely identified ligament
      injuries in 2 cases. Both imaging modalities confirmed the absence of cortical
      fractures in all 7 cases. For all findings, POCUS sensitivity and specificity
      were 57% and 86%, respectively. CONCLUSIONS: In this pilot study, we established
      that POCUS diagnosed the specific pathology of radiograph-negative lateral ankle
      injuries with poor sensitivity but good specificity. Thus, POCUS could act as a
      tool to exclude significant ligamentous and radiographically occult bony injury
      in these cases. A larger study is needed to validate the utility of POCUS for
      this common injury.

PMID- 28509685
TI  - Modeling Acute Traumatic Hemorrhagic Shock Injury: Challenges and Guidelines for
      Preclinical Studies.
AB  - Trauma is responsible for a large proportion of the world's burden of disease,
      and is by far the biggest killer of young adults. Hemorrhage is the leading cause
      of preventable death and its effects are directly correlated with the incidence
      multi-organ failure in survivors. Trauma research is challenging due to patient
      heterogeneity, limited randomized controlled trials, and in vitro studies that
      fail to mimic the systemic injury response. Preclinical research remains
      essential for mechanistic and therapeutic discovery. Yet modeling the
      multifaceted nature of traumatic injury poses important experimental and welfare
      challenges associated with the onset of injury and prehospital and intra
      operative care, the limited inter-species validation of coagulation profiles, the
      use of anesthesia/analgesia, and its impact on the systemic response to trauma;
      and the challenge of sustaining intensive care in recovery models. Proper model
      selection depends on the purpose of a given model and the criteria by which the
      experimental readouts will be clinically relevant. Such complexity warrants
      further refinement of experimental methodology and outcome measures to improve
      its clinical efficacy, while ensuring animal well-being. We review the
      experimental methodologies currently used for modeling traumatic hemorrhagic
      shock and addressing their impact on clinical translation. The aim of the review
      is to improve transparency and form a consensus when reporting methodology in
      trauma modeling.

PMID- 28509687
TI  - Trust in the Medical Profession Among Adolescents in an Emergency Department.
AB  - OBJECTIVE: The aims of this study were to assess trust in the medical profession
      among adolescents in an urban pediatric emergency department (ED) and explore
      factors associated with trust. METHODS: We used a computerized survey to assess
      personal trust, perceived trust among family/friends, health care use, general
      and genital examination preferences, health behaviors, and demographics among
      youth aged 14 to 19 years. The primary outcome was the mean composite score of a
      validated 5-item scale. Responses were summed (range, 5-25); higher scores
      indicated greater trust. We compared trust between subgroups using the t test for
      independent samples. RESULTS: We enrolled 150 adolescents (80% of approached);
      146 completed the survey (mean age, 15.6 y; 40% male; 36% African American, 40%
      white, 17% Hispanic; 29% commercial insurance). The mean trust score was 19.51 +/
      3.1 (range, 7-25), indicating a fairly high level of trust. Trust was not
      associated with race, ethnicity, sex, type of insurance, or health care use. The
      mean score for those with high paternal trust was higher than those reporting low
      paternal trust (19.8 +/- 2.2 vs 15.3 +/- 5.7, P = 0.02); there was no association
      with perceived trust among mothers or friends. Preference for a chaperoned
      genital examination was associated with lower trust and female sex. CONCLUSIONS:
      Adolescents in this ED reported high levels of trust in the medical profession,
      and trust was not associated with race, ethnicity, sex, insurance, or health care
      use. Youth with lower trust preferred chaperoned genital examinations. Adolescent
      trust may be influenced by perceived trust among important adults. Exploration of
      these associations seems warranted to facilitate optimal sexual health outcomes.

PMID- 28509688
TI  - A prevalence study of thoracic scoliosis in Chilean patients aged 10-20 years
      using chest radiographs as a screening tool.
AB  - To determine the prevalence of thoracic scoliosis in patients 10-20 years old
      using radiographs as a screening tool, we studied 783 patients who obtained chest
      radiographs for nonspinal reasons. We measured thoracic curvature in coronal and
      sagittal planes; we determined whether age, sex, and sagittal curvature predicted
      the coronal curvature. The prevalence of scoliosis was 9.3%: 7.0% had curvatures
      10 degrees -20 degrees ; 1.0% had curvatures 20 degrees -30 degrees ; and 1.3%
      had curvatures of at least 30 degrees . Females (13%) presented larger prevalence
      of scoliosis than males (4.8%) (P<0.01), also with a larger proportion of larger
      curvatures. Sex and thoracic kyphosis were independent predictors of the coronal
      curvature, age was not.

PMID- 28509689
TI  - Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai
      population.
AB  - BACKGROUND: Allopurinol is one of the most common causes of severe cutaneous
      adverse drug reactions (SCARs) including drug reactions with eosinophilia and
      systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal
      necrolysis (TEN). This study identified the risk factors associated with the
      development of allopurinol-induced SCARs in a Thai population. PATIENTS AND
      METHODS: Eighty-six allopurinol-induced SCARs (i.e. 19 DRESS and 67 SJS/TEN) and
      182 allopurinol-tolerant patients were enrolled in the study. The HLA-B*58:01
      allele was determined. Clinical and medicinal data were collected. RESULTS:
      Results from multivariate analysis showed that only the HLA-B*58:01 and female
      sex were identified as risk factors of allopurinol-induced SCARs in this Thai
      population. Patients who carried the HLA-B*58:01 allele were at a higher risk of
      allopurinol-induced DRESS [odds ratio (OR)=149.2, 95% confidence interval
      (CI)=24.0-infinity, P<1.00*10]. Similar results were observed in allopurinol
      induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69*10). The risk of allopurinol
      induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6,
      P=1.44*10). The overall mortality rate of allopurinol-induced SCARs was 11.39%
      and a higher mortality rate was observed in elderly women. CONCLUSION: Among the
      risk factors identified, the HLA-B*58:01 allele had the greatest impact on the
      development of both phenotypes of allopurinol-induced SCARs in this studied Thai
      population. In case HLA-B*58:01 genotyping cannot be accessed, close monitoring
      of allopurinol usage, especially in elderly women with impaired renal function,
      is necessary to reduce the mortality rate of these life-threatening SCARs.

PMID- 28509690
TI  - Genetics and its potential to improve type 1 diabetes care.
AB  - PURPOSE OF REVIEW: The genetic basis of type 1 diabetes (T1D) is being
      characterized through DNA sequence variation and cell type specificity. This
      review discusses the current understanding of the genes and variants implicated
      in risk of T1D and how genetic information can be used in prediction,
      intervention and components of clinical care. RECENT FINDINGS: Fine mapping and
      functional studies has provided resolution of the heritable basis of T1D risk,
      incorporating novel insights on the dominant role of human leukocyte antigen
      (HLA) genes as well as the lesser impact of non-HLA genes. Evaluation of T1D
      associated single nucleotide polymorphisms (SNPs), there is enrichment of genetic
      effects restricted to specific immune cell types (CD4 and CD8 T cells, CD19 B
      cells and CD34 stem cells), suggesting pathways to improved prediction. In
      addition, T1D-associated SNPs have been used to generate genetic risk scores
      (GRS) as a tool to distinguish T1D from type 2 diabetes (T2D) and to provide
      prediagnostic data to target those for autoimmunity screening (e.g. islet
      autoantibodies) as a prelude for continuous monitoring and entry into
      intervention trials. SUMMARY: Genetic susceptibility accounts for nearly one-half
      of the risk for T1D. Although the T1D-associated SNPs in white populations
      account for nearly 90% of the genetic risk, with high sensitivity and
      specificity, the low prevalence of T1D makes the T1D GRS of limited utility.
      However, identifying those with highest genetic risk may permit early and
      targeted immune monitoring to diagnose T1D months prior to clinical onset.

PMID- 28509693
TI  - Microcirculatory Effects of Botulinum Toxin A in the Rat: Acute and Chronic
      Vasodilation.
AB  - BACKGROUND: Botulinum toxin-A (BTX) has numerous cosmetic and therapeutic
      applications. Our previous studies have found that BTX augments pedicled flap
      survival through both vasodilatory effects and attenuation of the inflammatory
      response to ischemia in the rat. This study examines the effect of chronic BTX on
      microcirculatory vascular tone and its response to acute topical vasodilators in
      muscle flaps. METHODS: The spinotrapezius muscle of Sprague-Dawley rats underwent
      a single 2-week pretreatment of 0.2 mL saline either with (n = 5) or without (n =
      5) 2u BTX. After surgical elevation, an arcade arteriole was observed using a
      video caliper device. Vessel diameter was measured at 30-second intervals after
      sequential superfusion of nitroglycerin (100 and 200 MUg/mL), multiple
      concentrations of lidocaine, and a combination of adenosine (10 MUM) and
      nitroprusside (10 MUM) to induce maximum dilation. RESULTS: Baseline and dilation
      diameters were expressed as ratios of pharmacologically induced maximum dilation,
      whereas percent dilation was defined as the change in diameter over baseline
      diameter. We found a significant increase in resting diameter with BTX
      pretreatment (P = 0.0028). Compared with the control group, mean baseline
      diameter was 15% greater, and percent dilation was 25% less in BTX-pretreated
      flaps. There was no significant relationship between BTX pretreatment and
      dilation diameter (P = 0.2895) after adjusting for the effect of acute
      vasodilators. CONCLUSIONS: Pretreatment with BTX may induce the arteriolar
      resting diameter to be closer to their maximum potential diameter. Additionally,
      BTX does not display a synergistic effect with topical vasodilators on
      vasodilation.

PMID- 28509691
TI  - Development of glucose-responsive 'smart' insulin systems.
AB  - PURPOSE OF REVIEW: The complexity of modern insulin-based therapy for type I and
      type II diabetes mellitus and the risks associated with excursions in blood
      glucose concentration (hyperglycemia and hypoglycemia) have motivated the
      development of 'smart insulin' technologies (glucose-responsive insulin, GRI).
      Such analogs or delivery systems are entities that provide insulin activity
      proportional to the glycemic state of the patient without external monitoring by
      the patient or healthcare provider. The present review describes the relevant
      historical background to modern GRI technologies and highlights three distinct
      approaches: coupling of continuous glucose monitoring (CGM) to deliver devices
      (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation
      of insulin, and molecular modification of insulin itself. RECENT FINDINGS: Recent
      advances in GRI research utilizing each of the three approaches are illustrated;
      these include newly developed algorithms for CGM-based insulin delivery systems,
      glucose-sensitive modifications of existing clinical analogs, newly developed
      hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived
      pancreatic beta cells. SUMMARY: Although GRI technologies have yet to be
      perfected, the recent advances across several scientific disciplines that are
      described in this review have provided a path towards their clinical
      implementation.

PMID- 28509692
TI  - T1D Autoantibodies: room for improvement?
AB  - PURPOSE OF REVIEW: Type 1 diabetes (T1D) is now predictable by measuring major
      islet autoantibodies (IAbs) against insulin and other pancreatic beta cells
      proteins including GAD65 (GADA), islet antigen 2 (IA-2A), and zinc transporter 8
      (ZnT8A). The assay technology for IAbs has made great progress; however, several
      important aspects still need to be addressed and improved. RECENT FINDINGS:
      Currently a radio-binding assay has been well established as the 'gold' standard
      assay for all four IAbs. New generation of nonradioactive IAb assay with
      electrochemiluminescence technology has been shown to further improve sensitivity
      and disease specificity. Recently, multiplexed assays have opened the possibility
      of more efficient screening in large populations. Identification of potential new
      autoantibodies to neo-antigens or neo-epitopes posttranslational modification is
      a new important field to be explored. SUMMARY: Individuals having a single
      positive autoantibody are at low risk for progression to T1D, whereas individuals
      expressing two or more positive autoantibodies, especially on multiple tests over
      time, have nearly 100% risk of developing clinical T1D when followed for over two
      decades. More efficient and cost effective IAb assays will hopefully lead to
      point-of-care screening in the general population.

PMID- 28509695
TI  - A Novel Augmented Reality-Based Navigation System in Perforator Flap
      Transplantation - A Feasibility Study.
AB  - BACKGROUND: In perforator flap transplantation, dissection of the perforator is
      an important but difficult procedure because of the high variability in vascular
      anatomy. Preoperative imaging techniques could provide substantial information
      about vascular anatomy; however, it cannot provide direct guidance for surgeons
      during the operation. In this study, a navigation system (NS) was established to
      overlie a vascular map on surgical sites to further provide a direct guide for
      perforator flap transplantation. METHODS: The NS was established based on
      computed tomographic angiography and augmented reality techniques. A virtual
      vascular map was reconstructed according to computed tomographic angiography data
      and projected onto real patient images using ARToolKit software. Additionally, a
      screw-fixation marker holder was created to facilitate registration. With the use
      of a tracking and display system, we conducted the NS on an animal model and
      measured the system error on a rapid prototyping model. RESULTS: The NS
      assistance allowed for correct identification, as well as a safe and precise
      dissection of the perforator. The mean value of the system error was determined
      to be 3.474 +/- 1.546 mm. CONCLUSIONS: Augmented reality-based NS can provide
      precise navigation information by directly displaying a 3-dimensional individual
      anatomical virtual model onto the operative field in real time. It will allow
      rapid identification and safe dissection of a perforator in free flap
      transplantation surgery.

PMID- 28509694
TI  - Does the Use of Acellular Dermal Matrix Increase Postoperative Complications of
      the First-Stage Reconstruction of Immediate Expander-Implant Breast
      Reconstruction: A Matched Cohort Study.
AB  - PURPOSE: Controversy exists regarding complications associated with the use of
      acellular dermal matrix (ADM). This likely stems from the heterogeneous and
      unmatched patient characteristics in study groups. The purpose of this study was
      to analyze complications in a matched cohort to identify whether ADM use
      increased postoperative complications of the first-stage immediate expander
      implant breast reconstructions. METHODS: A retrospective matched-cohort study was
      performed. We retrospectively reviewed prospectively collected data from patients
      who underwent immediate expander-implant breast reconstruction after mastectomy
      between February 2010 and January 2016. Independent variables included clinical
      characteristics, mastectomy weight, mastectomy type, expander size, initial
      inflation volume, number of days to drain removal, and adjuvant or neoadjuvant
      therapies. Different independent variables between the ADM and non-ADM groups
      were used for propensity score matching. After matching, a pairwise comparison of
      the 2 cohorts' independent variables was carried out using the Wilcoxon signed
      rank test and McNemar test. Incidence of complications was evaluated for the 2
      matched cohorts. To adjust for ablative and reconstructive surgeons, a
      multivariable generalized estimating equation analysis was performed. RESULTS: A
      total of 574 immediate expander-implant breast reconstructions in 533 patients
      were included in this study. We identified 398 reconstructions (199 for each
      group; ADM and non-ADM group) of matched cohorts using propensity score matching.
      Characteristics were similar between the 2 matched cohorts. In the matched
      analysis, there were no significant differences in the rate of skin flap
      complications (16.1% vs 16.1%, P > 0.999), seroma (4.0% vs 8.5%, P = 0.065),
      infection (3.0% vs 3.5%, P = 0.781), and overall complications (21.1% vs 26.1%, P
      = 0.251). Acellular dermal matrix was not associated with increased risk of
      complication when ablative and reconstructive surgeon factors were considered in
      a multivariable analysis (P = 0.511). CONCLUSIONS: A matched cohort analysis
      demonstrated that ADM usage is not associated with an increased risk of
      complications, including skin flap complications, seroma, and infection. Our
      result suggests that ADM can be safely used in immediate expander-implant breast
      reconstruction when necessary.

PMID- 28509696
TI  - On-Top Index Pollicization After a Partial Amputation of a Syndactylized
      Hypoplastic Thumb in a Patient With Townes-Brocks Syndrome.
AB  - Townes-Brocks syndrome is a rare autosomal dominant syndrome characterized by
      multiple malformations, including thumb anomalies. Thumb hypoplasia poses a
      specific problem, where a deficient thumb creates a significant handicap in hand
      function. The treatment goal is enabling pinch and grip activity, and the
      preferred procedure for a severely hypoplastic thumb is index finger
      pollicization. We present a case of on-top index pollicization in a 10-year-old,
      after a partial amputation of a previously syndactylized hypoplastic thumb, with
      a well-formed first carpometacarpal joint. The decision to proceed with
      pollicization was made after considering second toe-to-hand transfer and a
      standard pollicization with an amputation of the thumb remnants. Six months after
      the procedure, the outcome was evaluated as "good" (19 points) with Percival's
      assessment method. The patient uses the operated hand in all activities of daily
      life and is doing well in school. This patient's diagnosis of Townes-Brocks
      syndrome was confirmed with genetic testing, which gives grounds and incentive to
      further investigate other possible related conditions, and provide genetic
      counselling and risk assessment. In reconstruction of complex thumb
      malformations, especially after previous multiple operations, an individually
      tailored reconstruction plan, sometimes involving modifications of standard
      reconstructive procedures, is paramount in achieving good results.

PMID- 28509697
TI  - Repair of Oropharyngeal Stenosis With Bilateral Buccal Myomucosal Flaps.
AB  - Oropharyngeal stenosis (OPS) is a rare postoperative complication of
      adenotonsillectomy that can be a source of considerable patient distress and
      morbidity. Circumferential scarring of the soft palate and tonsillar pillars
      leads to narrowing of the oropharyngeal aperture. This case report describes the
      novel use of bilateral buccal myomucosal flaps for the repair of postoperative
      OPS in a 20-year-old woman presenting with dysphagia, odynophagia, dyspnea, and
      intermittent hypernasal speech. Postoperatively, the patient noted immediate
      improvement of her symptoms. At 1-month follow-up, she noted complete resolution
      of her symptoms with no dysphagia, nasal regurgitation, speaking difficulty,
      dyspnea, or gagging. The buccal flaps were well healed and completely intact,
      maintaining appropriate height of the tonsillar pillars. The buccal myomucosal
      flap is an effective tool for numerous palatal and oropharyngeal abnormalities
      and, as described in this case study, is a reliable, safe, and effective
      technique that can be considered for the reconstruction of postsurgical OPS.

PMID- 28509698
TI  - A Meta-analysis of Studies Comparing Outcomes of Diverse Acellular Dermal
      Matrices for Implant-Based Breast Reconstruction.
AB  - BACKGROUND: The current diversity of the available acellular dermal matrix (ADM)
      materials for implant-based breast reconstruction raises the issue of whether
      there are any differences in postoperative outcomes according to the kind of ADM
      used. The present meta-analysis aimed to investigate whether choice of ADM
      products can affect outcomes. METHODS: Studies that used multiple kinds of ADM
      products for implant-based breast reconstruction and compared outcomes between
      them were searched. Outcomes of interest were rates of postoperative
      complications: infection, seroma, mastectomy flap necrosis, reconstruction
      failure, and overall complications. RESULTS: A total of 17 studies met the
      selection criteria. There was only 1 randomized controlled trial, and the other
      16 studies had retrospective designs. Comparison of FlexHD, DermaMatrix, and
      ready-to-use AlloDerm with freeze-dried AlloDerm was conducted in multiple
      studies and could be meta-analyzed, in which 12 studies participated. In the meta
      analysis comparing FlexHD and freeze-dried AlloDerm, using the results of 6
      studies, both products showed similar pooled risks for all kinds of
      complications. When comparing DermaMatrix and freeze-dried AlloDerm with the
      results from 4 studies, there were also no differences between the pooled risks
      of complications of the two. Similarly, the meta-analysis of 4 studies comparing
      ready-to-use and freeze-dried AlloDerm demonstrated that the pooled risks for the
      complications did not differ. CONCLUSIONS: This meta-analysis demonstrates that
      the 3 recently invented, human cadaveric skin-based products of FlexHD,
      DermaMatrix, and ready-to-use AlloDerm have similar risks of complications
      compared with those of freeze-dried AlloDerm, which has been used for longer.
      However, as most studies had low levels of evidence, further investigations are
      needed.

PMID- 28509700
TI  - Letter to the Editor: Stopping the Bleeding Is Not Enough.

PMID- 28509699
TI  - Penis Transplantation: First US Experience.
AB  - OBJECTIVE: We describe the first successful penis transplant in the United States
      in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND:
      Penis transplantation represents a new paradigm in restoring anatomic appearance,
      urine conduit, and sexual function after genitourinary tissue loss. To date, only
      2 penis transplants have been performed worldwide. METHODS: After institutional
      review board approval, extensive medical, surgical, and radiological evaluations
      of the patient were performed. His candidacy was reviewed by a multidisciplinary
      team of surgeons, physicians, psychiatrists, social workers, and nurse
      coordinators. After appropriate donor identification and recipient induction with
      antithymocyte globulin, allograft procurement and recipient preparation took
      place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal
      arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a
      donor skin pedicle as the composite allograft. Maintenance immunosuppression
      consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS:
      Intraoperative, the allograft had excellent capillary refill and strong Doppler
      signals after revascularization. Operative reinterventions on postoperative days
      (PODs) 2 and 13 were required for hematoma evacuation and skin eschar
      debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and
      the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff
      I), progressed by POD 32 (Banff III), and required a repeat course of
      methylprednisolone and antithymocyte globulin. At 7 months, the patient has
      recovered partial sensation of the penile shaft and has spontaneous penile
      tumescence. Our patient reports increased overall health satisfaction, dramatic
      improvement of self-image, and optimism for the future. CONCLUSIONS: We have
      shown that it is feasible to perform penile transplantation with excellent
      results. Furthermore, this experience demonstrates that penile transplantation
      can be successfully performed with conventional immunosuppression. We propose
      that our successful penile transplantation pilot experience represents a proof of
      concept for an evolution in reconstructive transplantation.

PMID- 28509701
TI  - Educational Gaps in Molecular Diagnostics, Genomics, and Personalized Medicine in
      Dermatopathology Training: A Survey of U.S. Dermatopathology Fellowship Program
      Directors.
AB  - BACKGROUND: Molecular technologies offer clinicians the tools to provide high
      quality, cost-effective patient care. We evaluated education focused on molecular
      diagnostics, genomics, and personalized medicine in dermatopathology fellowship
      training. DESIGN: A 20-question online survey was emailed to all (n = 53)
      Accreditation Council for Graduate Medical Education (ACGME)-accredited
      dermatopathology training programs in the United States. RESULTS: Thirty-one of
      53 program directors responded (response rate = 58%). Molecular training is
      undertaken in 74% of responding dermatopathology fellowships, with levels of
      instruction varying among dermatology-based and pathology-based programs.
      Education differed for dermatology- and pathology-trained fellows in
      approximately one-fifth (19%) of programs. Almost half (48%) of responding
      program directors believe that fellows are not currently receiving adequate
      molecular education, although the majority (97%) expect to incorporate additional
      instruction in the next 2-5 years. Factors influencing the incorporation of
      relevant education include perceived clinical utility and Accreditation Council
      for Graduate Medical Education/residency review committee (RRC) requirements.
      Potential benefits of molecular education include increased medical knowledge,
      improved patient care, and promotion of effective communication with other
      healthcare professionals. More than two-thirds (68%) of responding program
      directors believe that instruction in molecular technologies should be required
      in dermatopathology fellowship training. CONCLUSIONS: Although all responding
      dermatopathology fellowship program directors agreed that molecular education is
      important, only a little over half of survey participants believe that their
      fellows receive adequate instruction. This represents an important educational
      gap. Discussion among those who oversee fellow education is necessary to best
      integrate and evaluate teaching of molecular dermatopathology.

PMID- 28509702
TI  - Accordion music from the heart: dynamic coronary artery compression.

PMID- 28509703
TI  - Pathway for the Management of Atrial Fibrillation and Atrial Flutter.
AB  - Atrial fibrillation (AF) is the most common cardiac rhythm disturbance
      encountered in clinical practice, and its prevalence is increasing as the
      population ages. The American College of Cardiology, the American Heart
      Association, and the European Society of Cardiology established guidelines for
      the management of patients with AF. Atrial flutter (Afl) is less common and is
      often associated with or preceded by AF or occurs in an isolated pattern. A major
      limitation of the currently published guidelines for the management of patients
      with AF and Afl is their complexity, the fact that official guidelines are
      published separately for each of these arrhythmias, and that they were published
      several years ago. To address these deficiencies, we have developed a novel
      pathway for the management of AF and Afl. The pathway has been designated with
      the acronym RACE, which reflects the 4 main components in patient management:
      rate control, anticoagulation therapy, cardioversion, and
      electrophysiology/antiarrhythmic medication. This pathway is an attempt to
      incorporate, in a user-friendly format, the key concepts of the initial diagnosis
      and management of these prevalent arrhythmias. This is followed by a
      comprehensive guideline for therapy using the RACE acronym.

PMID- 28509704
TI  - Effectiveness of 2-hour Troponin in High-risk Patients With Suspected Acute
      Coronary Syndrome.
AB  - BACKGROUND: Research has shown the safety and effectiveness of drawing a standard
      troponin level at presentation and again at 2 hours in only low-risk patients.
      Because high-sensitivity troponins are not currently approved in the United
      States, we studied the utility of a standard troponin that is presently in use.
      Our goal was to determine if 2-hour standard troponin would be safe and effective
      in the evaluation of a high-risk cohort of patients never studied previously.
      METHODS: We conducted a single-center prospective observational study of adult
      patients presenting to the emergency department with signs and symptoms
      suggestive of acute coronary syndrome. Patients were defined as high risk if the
      attending physician planned to admit or transfer the patient to the observation
      unit. History, Electrocardiography, Age, Risk factors, Troponin scores were
      calculated on all patients to provide verification that the individuals were high
      risk. The primary outcome was a composite of 30-day myocardial infarction, death,
      cardiac arrest with return of spontaneous circulation, or dysrhythmia. The
      secondary outcome was 30-day revascularization. RESULTS: We included a total of
      122 patients with an average follow-up of 112 days (minimum 30 days). A total of
      86% of cases had History, Electrocardiography, Age, Risk factors, Troponin scores
      >=4. The primary outcome was met in 22 (18%) patients, and the secondary outcome
      occurred in 7 (5.7%) patients. The negative predictive value of negative 2-hour
      troponins along with no significant delta troponin rise was 98.7%. CONCLUSIONS:
      Discharging patients thought to be high risk who have negative troponins at 0 and
      2 hours and no delta troponin rise appears safe. No deaths occurred in follow-up.
      Larger studies are warranted.

PMID- 28509705
TI  - Yield of Cardiac Magnetic Resonance Imaging in Patients With Acute Coronary
      Syndrome and No Obstructive Coronary Artery Disease.
AB  - PURPOSE: Ten percent to 25% of women and 6%-10% of men with acute coronary
      syndrome (ACS) are found to have no obstructive coronary artery disease (CAD) on
      coronary computed tomography angiogram or invasive coronary angiography. The
      etiology of presentation is often unclear. We examined the diagnostic yield of
      cardiac magnetic resonance imaging (CMR) in patients with signs and symptoms
      suggestive of an ACS and no obstructive CAD. METHODS: We retrospectively studied
      patients with signs and symptoms suggestive of an ACS and no obstructive CAD on
      coronary computed tomography angiogram or invasive coronary angiography who had
      CMR performed at St. Paul's Hospital, British Columbia, Canada, from 2013 to
      2015. No obstructive CAD was defined as <50% stenosis in any epicardial artery.
      We compared CMR diagnostic yield in troponin-positive and troponin-negative
      patients and determined the etiology of presentation in each category. We also
      examined gender differences. RESULTS: Ninety-eight patients met inclusion
      criteria. The average age was 55.8 years, 70% were female, and 60% were troponin
      positive upon presentation. Abnormal CMR was observed in 35.7% of patients,
      yielding a diagnosis in 27.9% of females and 53.5% of males (P = 0.02). Troponin
      positive patients had a significantly higher prevalence of an abnormal CMR than
      did troponin-negative patients (44.1% vs. 23.1%; P = 0.03). Myocarditis was more
      common in troponin-positive patients (25.4% vs. 2.6%; P = 0.002). CONCLUSIONS:
      Forty-four percent of patients with positive troponin and with signs and symptoms
      suggestive of an ACS, no obstructive CAD on invasive coronary angiography or
      coronary computed tomography angiogram, and unclear diagnosis had abnormalities
      on CMR that identified the diagnosis. CMR should be considered in patients with
      positive troponin values when the etiology for their presentation is unclear.

PMID- 28509706
TI  - Length of Stay, Mortality, Cost, and Perceptions of Care Associated With
      Transition From an Open to Closed Staffing Model in the Cardiac Intensive Care
      Unit.
AB  - BACKGROUND: Organizational models in the intensive care unit (ICU) have
      classically been described as either closed or open, depending on the presence or
      absence of a dedicated ICU team. Although a closed model has been shown to
      improve patient outcomes in medical and surgical ICUs, the merits of various care
      models have not been previously explored in the cardiac ICU (CICU) setting.
      METHODS: From November 2012 to March 2014, data were prospectively collected on
      all admissions before and after transition from an open to closed CICU at our
      institution. Baseline clinical variables, illness severity, admission and
      discharge diagnoses, resource use, and outcomes were recorded. Anonymous surveys
      were also collected from nursing and resident trainee participants to evaluate
      the influence of unit structure on perceptions of care. Descriptive statistics
      were used, and logistic regression modeling was performed to examine the impact
      of unit structure on mortality. RESULTS: The study consisted of 670 patients, 332
      (49.6%) of whom were admitted to the open CICU model and 338 (50.4%) of whom were
      admitted to the closed model. Neither CICU nor hospital mortality differed
      between the open and closed units, though length of stay was shorter in the
      closed CICU. Additionally, nurses and resident trainees reported that the closed
      CICU allowed for better communication, collaboration, and education. CONCLUSIONS:
      Although there was no significant impact of unit structure on patient outcomes in
      this single-center study, the closed CICU model was associated with better
      perceptions of care.

PMID- 28509708
TI  - PVCs, PVC-Induced Cardiomyopathy, and the Role of Catheter Ablation.
AB  - Premature ventricular contractions (PVCs) are common arrhythmias noticed in the
      clinical setting because of premature depolarization of the ventricular myocytes.
      Although often thought to be reflective of underlying disease rather than
      intrinsically harmful, PVCs have recently been linked with worse outcomes in
      patients without significant cardiac disease. Long-term exposure to a high PVC
      burden can lead to the development of PVC-induced cardiomyopathy. The
      pathogenesis of this condition is poorly understood at the current time. Many
      studies have suggested that catheter ablation of these PVCs may result in
      reversal of the PVC-induced cardiomyopathy. This article will go over the natural
      history of PVCs and PVC-induced cardiomyopathy, as well as review the current
      literature on the role of catheter ablation in treating PVC-induced
      cardiomyopathy.

PMID- 28509709
TI  - Utility of SOFA and Delta-SOFA scores for predicting outcome in critically ill
      patients from the emergency department.
AB  - OBJECTIVE: The condition of critically ill patients in the emergency department
      (ED) varies from moment to moment. The aims of this study are to quantify
      sequential organ failure assessment (SOFA) and changes in SOFA scores over time
      and determine its prognostic impact. PATIENTS AND METHODS: This is a prospective
      observational cohort study. We included 269 patients consecutively admitted to
      the ICU from the ED over 18 months. The SOFA scores at ED admission (ED-SOFA) and
      ICU admission (ICU-SOFA) were obtained. Relative changes in SOFA scores were
      calculated as follows: Delta-SOFA=ICU-SOFA-ED-SOFA. Patients were divided into
      two groups depending on the Delta-SOFA score: (a) Delta-SOFA=0-1; and (b) Delta
      SOFA more than or equal to 2. RESULTS: The median ED-SOFA score was two points
      (interquartile range: 1-4.5) and the Delta-SOFA score was 2 points (interquartile
      range: 0-3). The Delta-SOFA score was more powerful (area under the curve: 0.81)
      than the ED-SOFA score (area under the curve: 0.75) in predicting hospital
      mortality. Sixteen (6%) patients had a Delta-SOFA score less than 0, 116 (43%)
      patients had a Delta-SOFA=0-1, and 137 (51%) patients had a Delta-SOFA of at
      least 2 points. The probability of being alive at hospital discharge was 51 and
      86.5% in Delta-SOFA of at least 2 and Delta-SOFA=0-1 groups, respectively
      (P<0.001). Risk factors for an increase of two or more SOFA points were age,
      cirrhosis, a diagnosis of sepsis, and a prolonged ED stay. CONCLUSION: SOFA and
      changes in the SOFA score over time are potentially useful tools for risk
      stratification when applied to critically ill patients admitted to ICUs from the
      ED.

PMID- 28509707
TI  - Burden of Psychosocial and Cognitive Impairment in Patients With Atrial
      Fibrillation.
AB  - BACKGROUND: Impairments in psychosocial status and cognition relate to poor
      clinical outcomes in patients with atrial fibrillation (AF). However, how often
      these conditions co-occur and associations between burden of psychosocial and
      cognitive impairment and quality of life (QoL) have not been systematically
      examined in patients with AF. METHODS: A total of 218 patients with symptomatic
      AF were enrolled in a prospective study of AF and psychosocial factors between
      May 2013 and October 2014 at the University of Massachusetts Medical Center.
      Cognitive function, depression, and anxiety were assessed at baseline and AF
      specific QoL was assessed 6 months after enrollment using validated instruments.
      Demographic and clinical information were obtained from a structured interview
      and medical record review. RESULTS: The mean age of the study participants was
      63.5 +/- 10.2 years, 35% were male, and 81% had paroxysmal AF. Prevalences of
      impairment in 1, 2, and 3 psychosocial/cognitive domains (eg, depression,
      anxiety, or cognition) were 75 (34.4%), 51 (23.4%), and 16 (7.3%), respectively.
      Patients with co-occurring psychosocial/cognitive impairments (eg, >1 domain)
      were older, more likely to smoke, had less education, and were more likely to
      have heart failure (all P < 0.05). Compared with participants with no
      psychosocial/cognitive impairments, AF-specific QoL at 6 months was significantly
      poorer among participants with baseline impairment in 2 (B = -13.6, 95% CI: -21.7
      to -5.4) or 3 (B = -15.1, 95% CI: -28.0 to -2.2) psychosocial/cognitive domains.
      CONCLUSION: Depression, anxiety, and impaired cognition were common in our cohort
      of patients with symptomatic AF and often co-occurred. Higher burden of
      psychosocial/cognitive impairment was associated with poorer AF-specific QoL.

PMID- 28509710
TI  - Ultrasound-guided pericardiocentesis: a novel parasternal approach.
AB  - OBJECTIVE: The aim of this study was to evaluate a novel pericardiocentesis
      technique using an in-plane parasternal medial-to-lateral approach with the use
      of a high-frequency probe in patients with cardiac tamponade. BACKGROUND:
      Echocardiography is pivotal in the diagnosis of pericardial effusion and
      tamponade physiology. Ultrasound guidance for pericardiocentesis is currently
      considered the standard of care. Several approaches have been described recently,
      which differ mainly on the site of puncture (subxiphoid, apical, or parasternal).
      Although they share the use of low-frequency probes, there is absence of complete
      control of needle trajectory and real-time needle visualization. An in-plane and
      real-time technique has only been described anecdotally. METHODS AND RESULTS: A
      retrospective analysis of 11 patients (63% men, mean age: 37.7+/-21.2 years)
      presenting with cardiac tamponade admitted to the tertiary-care emergency
      department and treated with parasternal medial-to-lateral in-plane
      pericardiocentesis was carried out. The underlying causes of cardiac tamponade
      were different among the population. All the pericardiocentesis were successfully
      performed in the emergency department, without complications, relieving the
      hemodynamic instability. The mean time taken to perform the eight-step procedure
      was 309+/-76.4 s, with no procedure-related complications. CONCLUSION: The
      parasternal medial-to-lateral in-plane pericardiocentesis is a new technique
      theoretically free of complications and it enables real-time monitoring of needle
      trajectory. For the first time, a pericardiocentesis approach with a medial-to
      lateral needle trajectory and real-time, in-plane, needle visualization was
      performed in a tamponade patient population.

PMID- 28509711
TI  - Trends in governance structure and activities among not-for-profit U.S.
      hospitals: 2009-2015.
AB  - BACKGROUND: In U.S. hospitals, boards of directors (BODs) have numerous
      governance responsibilities including overseeing hospital activities and guiding
      strategic decisions. BODs can help hospitals adapt to changes in their markets
      including those stemming from a shift from fee-for-service to value-based
      purchasing. The recent increase in market turbulence for hospitals has brought
      renewed attention to the work of BODs. PURPOSE: The aim of the study was to
      examine trends in hospital BOD structure and activities and determine whether
      these changes are commensurate with approaches designed to respond to market
      pressures. METHODOLOGY/APPROACH: We examined hospital level data from The
      Governance Institute Survey (2009, 2011, 2013, and 2015) and corresponding years
      of the American Hospital Association Annual Survey in a pooled, cross-sectional
      design. We conducted individual multivariate models with adjustments for hospital
      and market characteristics, comparing the changes in BOD structures,
      demographics, and activities over time. FINDINGS: The sample included 1,811
      hospital-year observations, including 682 unique facilities. We found that BODs
      in 2015 had less internal management (beta = -2.25, p < .001) and fewer employed
      and nonemployed physicians (beta = -8.28, p < .001) involved on the BOD.
      Moreover, compared to 2009, racial and ethnic minorities (2013 beta = 2.88, p <
      .001) and women (2013 beta = 1.60, p = .045; 2015 beta = 2.06, p = .049) on BODs
      increased over time. In addition, BODs were significantly less likely to spend
      time on the following activities in 2015, as compared to 2009: discussing
      strategy and setting policy (beta = -5.46, p = .002); receiving reports from
      management, board committees, and subsidiaries (beta = -29.04, p < .001); and
      educating board members (beta = -4.21, p < .001). Finally, BODs had no changes in
      the type of committees reported over time. PRACTICE IMPLICATIONS: Our results
      indicate that hospital BODs deploy various strategies to adapt to current market
      trends. Hospital decision-makers should be aware of the potential effects of
      board structure on organization's position in the changing health care market.

PMID- 28509712
TI  - Accelerating access and scale-up of optimized ART in low-income and middle-income
      countries: a call for a coordinated end-to-end approach.
AB  - PURPOSE OF REVIEW: To discuss how aligning the collective power of scientists,
      regulators, drug companies, donors, implementers and advocates to achieve a
      single goal - accelerating access to simpler, safer, more robust and more
      affordable HIV treatment - can rapidly advance antiretroviral optimization
      efforts and enable scale-up. RECENT FINDINGS: Harmonization of traditionally
      sequential processes can address the delays commonly experienced in introducing
      new products to low-income and middle-income countries, by facilitating an 'end
      to-end' approach that mitigates risk and encourages early planning for all
      aspects of product introduction. SUMMARY: Planning with the 'end-in-mind' can
      facilitate healthy markets, benefit the application of new technologies, and
      accelerate the development of improved products in parallel (versus traditionally
      sequential efforts).

PMID- 28509714
TI  - Preventing Occupational Skin Disease: A Review of Training Programs.
AB  - Occupational contact dermatitis (OCD) is a common occupational disease that
      impacts a variety of worker groups. Skin protection and disease prevention
      training programs have shown promise for improving prevention practices and
      reducing the incidence of OCD. This review details the features of training
      programs for primary prevention of OCD and identifies gaps in the literature.
      Twelve studies were identified for in-depth review: many studies included wet
      workers employed in health care, hairdressing, cleaning, and food preparation; 1
      program featured manufacturing workers. Few programs provided content on allergic
      contact dermatitis, and only 1 was evaluated for long-term effectiveness.
      Effective programs were similar in content, delivery method, and timing and were
      characterized by industry specificity, multimodal learning, participatory
      elements, skin care resource provision, repeated sessions, and management
      engagement. Long-term effectiveness, generalizability beyond OCD, workplace
      health and safety culture impact, and translation of programs in the North
      American context represent areas for future research.

PMID- 28509715
TI  - Epidemic of Isothiazolinone Allergy in North America: Prevalence Data From the
      North American Contact Dermatitis Group, 2013-2014.
AB  - BACKGROUND: Preservative sensitivity patterns evolve with changing use patterns
      in products. During the last decade, the use of methylisothiazolinone (MI) at
      higher concentrations in both leave-on and rinse-off products has significantly
      increased. This is the first North American Contact Dermatitis Group reporting
      cycle that includes both methylchloroisothiazolinone (MCI)/MI and MI data.
      OBJECTIVE: The aim of this study was to report the prevalence of isothiazolinone
      allergy (MCI/MI and MI) in the North American Contact Dermatitis Group patch-test
      population from January 1, 2013, to December 31, 2014. METHODS: At 13 centers in
      North America, 4860 patients were patch tested in a standardized manner with a
      series of 70 allergens, including MCI/MI 0.01% aqueous (aq) and MI 0.2% aq.
      RESULTS: Three hundred five patients (6.3%) had a positive reaction to MCI/MI;
      this is a significant increase from the previous cycle (5.0%, 2011-2012; P =
      0.011). Five hundred twenty-one patients (10.7%) had a positive reaction to MI.
      These 2 isothiazolinones were among the most common preservative allergens in the
      2013 to 2014 cycle; 11.9% of patch-tested individuals were allergic to 1 or both
      isothiazolinones. Individuals with MCI/MI and MI allergy were significantly more
      likely to have occupationally related skin disease (P < 0.0001) and hand
      dermatitis (P < 0.0001, P = 0.0474). CONCLUSIONS: The epidemic of isothiazolinone
      sensitivity documented in Europe is now in North America. Patch testing with only
      MCI/MI 0.01% aq will miss approximately half of isothiazolinone allergy cases,
      whereas testing with only MI 0.2% aq will miss approximately 10% of
      isothiazolinone allergy cases.

PMID- 28509716
TI  - Multicenter Patch Testing With Methylchloroisothizoline/Methylisothiazolinone in
      100 and 200 ppm Within the International Contact Dermatitis Research Group.
AB  - BACKGROUND: The preservative methylchloroisothiazolinone/methylisothiazolinone
      (MCI/MI) is a well-known contact sensitizer. Historically, there have been
      different opinions on the optimal patch test concentration of MCI/MI, and both
      0.01% and 0.02% aqueous (aq.) have been proposed. In 2011, based on literature
      reviews, it was recommended that the concentration of 0.02% aq. should be used in
      the international baseline series. OBJECTIVES: The aim of this study was to
      verify the recommendation from 2011 by comparing the patch test results from
      consecutive patch testing with MCI/MI 0.01% and 0.02% in clinics representing
      countries around the world. PATIENTS AND METHODS: Two thousand seven hundred
      three consecutive patients with dermatitis in 8 dermatology clinics representing
      8 countries were patch tested with MCI/MI 0.01% aq. and, in parallel with MCI/MI
      0.02% aq., provisionally included in the baseline series. RESULTS: Contact
      allergy to MCI/MI at 0.01% and 0.02% was found in 3.7% and 5.6% of the patients,
      respectively (P < 0.001). CONCLUSIONS: Methylchloroisothiazolinone/MI 0.02% aq.
      (dose, 6 MUg/cm) diagnoses significantly more contact allergy than 0.01% (dose, 3
      MUg/cm), without resulting in more adverse reactions.
      Methylchloroisothiazolinone/MI at 0.02% aq. should therefore be continuously used
      in the international baseline series.

PMID- 28509717
TI  - Unreported Sources of Nickel Exposure in Community-Based Facilities Frequented by
      Children.

PMID- 28509718
TI  - Contact Allergens in Food Handlers of Kashmir Valley in North India.

PMID- 28509719
TI  - The Importance of Factors Related to Nurse Retention: Using the Baptist Health
      Nurse Retention Questionnaire, Part 2.
AB  - OBJECTIVE: The purpose of this study was to examine the importance of factors
      related to nurse retention. BACKGROUND: Retaining nurses within the healthcare
      system is a challenge for hospital administrators. Understanding factors
      important to nurse retention is essential. METHODS: Responses of nurses (n = 279)
      to the Baptist Health Nurse Retention Questionnaire (BHNRQ) at a 391-bed
      Magnet(r) redesignated community hospital were analyzed to explore differences in
      importance scores of bedside nurses. RESULTS: The results demonstrate that each
      of the 12 items on the BHNRQ was moderately to highly important. A multivariate
      analysis of variance based on generation, degree, unit, and experience revealed
      no significant differences on subscale scores (nursing practice, management, and
      staffing). Themes derived from the comment section on the BHNRQ were consistent
      with quantitative findings. CONCLUSION: Clinical and managerial competence,
      engagement with their employees, and presence on the unit are keys to retaining a
      satisfied nursing workforce.

PMID- 28509720
TI  - Effects of RN Age and Experience on Transformational Leadership Practices.
AB  - OBJECTIVE: This study reported the evolution of transformational leadership (TL)
      practices and behaviors across years of age, management experience, and
      professional nursing practice within a professional nursing leadership
      organization. BACKGROUND: Recent studies of CNO TL found valuations peak near age
      60 years. This study reported on a wider range of management positions,
      correlating years of RN practice and management experience and age to TL metrics.
      METHOD: This study used Kouzes and Posner's Leadership Practices Inventory-Self
      Assessment (LPI-S) to survey a nursing leadership organization, the Association
      of California Nurse Leaders (ACNL). Anonymous responses were analyzed to identify
      leadership trends in age and years of professional service. RESULTS: On average,
      LPI-S metrics of leadership skills advance through years of management, RN
      experience, and age. The TL scores are statistically higher in most LPI-S
      categories for those with more than 30 years of RN or management experience.
      Decade-averaged LPI-S TL metrics in the ACNL survey evolve linearly throughout
      age before peaking in the decade from age 60 to 69 years. A similar evolution of
      TL metrics is seen in decades of either years of management experience or years
      of RN experience. Transformational leadership increased with nursing maturity
      particularly for LPI-S categories of "inspire a shared vision," "challenge the
      process," and "enable others to act." CONCLUSION: In the ACNL population studied,
      decade-averaged leadership metrics advanced. Leadership evolution with age in the
      broader RN population peaked in age bracket 60 to 69 years. The LPI-S averages
      declined when older than 70 years, coinciding with a shift from full-time work
      toward retirement and part-time employment.

PMID- 28509721
TI  - Bundled Payments for Care Improvement: Preparing for the Medical Diagnosis
      Related Groups.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services Innovation Center
      introduced the Bundled Payments for Care Improvement (BPCI) initiative in 2011 as
      1 strategy to encourage healthcare organizations and clinicians to improve
      healthcare delivery for patients, both when they are in the hospital and after
      they are discharged. Mercy Health Saint Mary's, a large urban academic medical
      center, engaged in BPCI primarily with a group of medical diagnosis-related
      groups (DRGs). OBJECTIVES: In this article, we describe our experience creating a
      system of response for the diverse people and diagnoses that fall into the
      medical DRG bundles and specifically identify organizational factors for enabling
      successful implementation of bundled payments. RESULTS: Our experience suggests
      that interprofessional collaboration enabled program success. CONCLUSIONS:
      Although still in its early phases, observations from our program's strategies
      and tactics may provide potential insights for organizations considering
      engagement in the BPCI initiative.

PMID- 28509722
TI  - Rationale for nebivolol/valsartan combination for hypertension: review of
      preclinical and clinical data.
AB  - : To treat hypertension, combining two or more antihypertensive drugs from
      different classes is often necessary. beta-Blockers and renin-angiotensin
      aldosterone system inhibitors, when combined, have been deemed 'less effective'
      based on partially overlapping mechanisms of action and limited evidence.
      Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a
      vasodilatory beta1-selective antagonist/beta3 agonist - and valsartan 80 mg, an
      angiotensin II receptor blocker, was US Food and Drug Administration-approved for
      hypertension. Pharmacological profiles of Neb and valsartan, alone and combined,
      are well characterized. In addition, a large 8-week randomized trial in stages I
      II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing
      efficacy for Neb/valsartan SPCs than component monotherapies with comparable
      tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented
      valsartan-induced increases in plasma renin, and a greater reduction in plasma
      aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This
      review summarizes preclinical and clinical evidence supporting Neb/valsartan as
      an efficacious and well tolerated combination treatment for hypertension.

PMID- 28509724
TI  - Associations between glycaemic deterioration and aortic stiffness and central
      blood pressure: the ADDITION-PRO Study.
AB  - OBJECTIVES: In the context of screening for diabetes, we examined levels of
      central haemodynamics among individuals with different levels of diabetes risk
      and analysed the impact of glycated haemoglobin A (HbA1c) and HbA1c changes on
      central haemodynamics. METHODS: A Danish population-based stepwise screening
      programme for diabetes including a diabetes risk score (DRS) questionnaire and
      glucose measurements identified seven groups of individuals at increasing levels
      of diabetes risk. After 7.8 years of follow-up, 2048 individuals underwent aortic
      stiffness assessment by carotid-femoral pulse wave velocity (aPWV) and assessment
      of central blood pressure (BP). We compared differences in central haemodynamics
      at follow-up between the diabetes risk groups and analysed the impact of HbA1c at
      screening and HbA1c change on central haemodynamics at follow-up adjusting for
      relevant confounders. RESULTS: At screening, median age was 59.0 years, and
      median HbA1c was 5.7%. At follow-up, median aPWV was 8.0 m/s, and median central
      SBP was 123.5 mmHg. Among individuals with high DRS, aPWV, central SBP and DBP,
      and pulse pressure were higher in individuals with impaired glucose tolerance
      than normal glucose tolerance. Per 1%-point higher HbA1c at screening, aPWV was
      0.23 m/s (95% confidence interval: 0.00; 0.46) higher, and central DBP was 1.35
      mmHg (95% confidence interval: 0.19; 2.51) lower, whereas HbA1c change was not
      associated with any of the central haemodynamics. CONCLUSION: Dysglycaemia is
      associated with future aortic stiffness. However, glycaemic deterioration over
      7.8 years does not affect aortic stiffness or central BP independently of other
      cardiometabolic risk factors.

PMID- 28509723
TI  - Determinants of retinal microvascular features and their relationships in two
      European populations.
AB  - OBJECTIVES: To examine factors influencing retinal vasculature in two
      environmentally contrasted, cross-sectional studies of adult participants of
      European descent and to estimate the extent and specificity of genetic
      contributions to each retinal vasculature feature. METHODS: Retinal images from
      1088 participants in the Orkney Complex Disease Study and 387 in the CROATIA
      Korcula study, taken using the same nonmydriatic camera system and graded by the
      same person, were evaluated. Using general linear models, we estimated the
      influence of an extensive range of systemic risk factors, calculated retinal
      traits heritabilities and genetic correlations. MAIN RESULTS: Systemic covariates
      explained little (<4%) of the variation in vessel tortuosity, substantially more
      (>10%, up to 31.7%) of the variation in vessel width and monofractal dimension.
      Suggestive not well trodden associations of biological interest included that of
      urate, tissue plasminogen activator and cardiac PR interval with arteriolar
      narrowing, that of carotid intima-media thickness with less-tortuous arterioles
      and of cardiac QT interval with more tortuous venules. The genetic underpinning
      of tortuosity is largely distinct from that of the other retinal vascular
      features, whereas that of fractal dimension and vessel width greatly overlaps.
      The previously recognized influence of ocular axial length on vessel widths was
      high and can be expected to lead to artefactual genetic associations [genetic
      correlation with central retinal arteriolar equivalent: -0.53 (standard error
      0.11)]. The significant genetic correlation between SBP and central retinal
      arteriolar equivalent, -0.53 (standard error 0.22) (after adjusting for age, sex
      and axial length of the eye), augurs more favourably for the discovery of genetic
      variants relevant to vascular physiology.

PMID- 28509725
TI  - Telmisartan and hydrochlorothiazide antihypertensive treatment in high sodium
      intake population: a randomized double-blind trial.
AB  - OBJECTIVES: To compare the blood pressure (BP)-lowering effects of telmisartan 40
      mg/day and hydrochlorothiazide (HCTZ) 25 mg/day in high sodium intake patients
      with mild-to-moderate hypertension in China. METHODS: In this randomized, double
      blind trial, eligible patients were randomly divided into telmisartan and HCTZ
      groups with three follow-ups scheduled on days 15, 30, and 60 after enrollment to
      compare BP decrease, hypokalemia, and other adverse events after intervention.
      RESULTS: A total of 1333 mild-to-moderate hypertensive patients with average
      sodium intake of 5909 mg/day were enrolled from 14 county hospitals in China.
      Baseline characteristics were well balanced. At 15, 30, and 60 days of follow-up,
      average SBP/DBP reduction in telmisartan and HCTZ group was 12.5/8.0, 14.3/9.1,
      12.8/7.2, 11.0/5.8, 13.6/7.1, and 11.5/5.3 mmHg, respectively. Telmisartan showed
      greater BP response than HCTZ at three visits, with statistical significance for
      DBP (P < 0.001) regardless of the adjustment for baseline BP, sodium excretion,
      and pulse pressure (PP). SBP reduction was positively related to increasing
      urinary sodium and PP levels for patients in both groups but increased faster
      with increasing PP in HCTZ than in telmisartan (P = 0.0238 for group * PP).
      Compared with telmisartan, HCTZ showed more hypokalemia (0.4 vs. 4.5%, P <
      0.001). CONCLUSION: Both telmisartan and HCTZ were effective for the treatment of
      hypertensive patients with high sodium intake. Telmisartan showed better DBP
      lowering effect and less hypokalemia than HCTZ among high sodium intake patients.
      Further studies are needed to evaluate the plausible superiority effect of
      hydrochlorothiazide among patients with large PP.

PMID- 28509726
TI  - Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of
      renal (pro)renin receptor and intrarenal renin-angiotensin system.
AB  - OBJECTIVES: Butyrate, a short-chain fatty acid, is the end product of the
      fermentation of complex carbohydrates by the gut microbiota. Recently, sodium
      butyrate (NaBu) has been found to play a protective role in a number of chronic
      diseases. However, it is still unclear whether NaBu has a therapeutic potential
      in hypertension. The present study was aimed to investigate the role of NaBu in
      angiotensin II (Ang II)-induced hypertension and to further explore the
      underlying mechanism. METHODS: Ang II was infused into uninephrectomized Sprague
      Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean
      arterial blood pressure was recorded by the telemetry system. Renal tissues,
      serum samples, and 24-h urine samples were collected to examine renal injury and
      the regulation of the (pro)renin receptor (PRR) and renin. RESULTS:
      Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced
      mean arterial pressure from 129 +/- 6 mmHg to 108 +/- 4 mmHg (P < 0.01). This
      corresponded with an improvement in Ang II-induced renal injury, including
      urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the
      expression of inflammatory mediators tumor necrosis factor alpha, interleukin 6.
      The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and
      the urinary excretion of soluble PRR, renin, and angiotensinogen were all
      increased by Ang II infusion but decreased by NaBu treatment. In cultured
      innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced
      expression of PRR and renin. CONCLUSION: These results demonstrate that NaBu
      exerts an antihypertensive action, likely by suppressing the PRR-mediated
      intrarenal renin-angiotensin system.

PMID- 28509727
TI  - Lower dementia risk with different classes of antihypertensive medication in
      older patients.
AB  - OBJECTIVE: Use of antihypertensive medication (AHM) is potentially associated
      with a reduced risk of dementia. Both calcium channel blockers (CCBs) and
      angiotensin receptor blockers (ARBs) are suggested to have a more pronounced
      protective effect. We aimed to study the association between different classes of
      AHM and dementia in older people. METHODS: A subgroup of community-dwelling older
      people using AHM included in the 'Prevention of Dementia by Intensive Vascular
      Care' randomized controlled trial was studied. Incident dementia rates in
      participants with different AHM classes (mono and combination therapy) were
      compared with dementia rates in participants with any other AHM. RESULTS: At
      baseline, 1951 participants (55.3%) used AHM [mean age, 74.4 year (SD 2.5); mean
      SBP, 156.4 mmHg (SD 21.5)]. In total, 986 participants (50.5%) used beta
      blockers, 798 diuretics (40.9%), 623 angiotensin- converting enzyme inhibitors
      (31.9%), 522 CCBs (26.8%), and 402 ARBs (20.6%). After 6.7 years (interquartile
      range 6.0-7.3) of follow-up, 136 participants (7.0%) developed dementia. Both use
      of CCBs [hazard ratio 0.56, 95% confidence interval (95% CI) 0.36-0.87] and ARBs
      (hazard ratio 0.60, 95% CI 0.37-0.98) were independently associated with a
      decreased risk of dementia. The association of CCBs with dementia was most
      apparent in participants without a history of cardiovascular disease (hazard
      ratio 0.38, 95% CI 0.18-0.81) and with uncontrolled hypertension (hazard ratio
      0.26, 95% CI 0.11-0.61). SBP was not significantly lower in participants using
      CCBs or ARBs. CONCLUSION: Both use of CCBs and ARBs are independently associated
      with a decreased risk of dementia in older people.

PMID- 28509728
TI  - Society of Critical Care Medicine Presidential Address-46th Annual Congress,
      January 2017, Honolulu, Hawaii.

PMID- 28509731
TI  - Greater Treatment Effect With Lower Disease Severity: VASST Insights.

PMID- 28509732
TI  - Stick to What You Know: Do Visiting Intensivists Worsen Outcomes?

PMID- 28509729
TI  - Generalizable Biomarkers in Critical Care: Toward Precision Medicine.

PMID- 28509733
TI  - Safe at First, But Not Reaching Second: Implications of Delayed Second Doses of
      Antimicrobials in Patients Presenting to Emergency Departments With Sepsis.

PMID- 28509730
TI  - American College of Critical Care Medicine Clinical Practice Parameters for
      Hemodynamic Support of Pediatric and Neonatal Septic Shock.
AB  - OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007
      guidelines for hemodynamic support of newborn and pediatric septic shock. Provide
      the 2014 update of the 2007 American College of Critical Care Medicine "Clinical
      Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock."
      DESIGN: Society of Critical Care Medicine members were identified from general
      solicitation at Society of Critical Care Medicine Educational and Scientific
      Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched
      by the Society of Critical Care Medicine librarian using the keywords: sepsis,
      septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric
      oxide, extracorporeal membrane oxygenation, and American College of Critical Care
      Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND
      MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated
      into Spanish and Portuguese, and incorporated into Society of Critical Care
      Medicine and American Heart Association/Pediatric Advanced Life Support
      sanctioned recommendations. The review of new literature highlights two tertiary
      pediatric centers that implemented quality improvement initiatives to improve
      early septic shock recognition and first-hour compliance to these guidelines.
      Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global
      Sepsis Initiative data in resource rich developed and developing nations further
      showed improved hospital mortality with compliance to first-hour and
      stabilization guideline recommendations. CONCLUSIONS: The major new
      recommendation in the 2014 update is consideration of institution-specific use of
      1) a "recognition bundle" containing a trigger tool for rapid identification of
      patients with septic shock, 2) a "resuscitation and stabilization bundle" to help
      adherence to best practice principles, and 3) a "performance bundle" to identify
      and overcome perceived barriers to the pursuit of best practice principles.

PMID- 28509734
TI  - Inflammatory Signatures in ICU-Acquired Weakness.

PMID- 28509735
TI  - The Road to Unintended Consequences Is Paved With Good Intentions.

PMID- 28509736
TI  - Progressive Mobility Program in a Neuro-ICU: What Makes It Different?

PMID- 28509737
TI  - Noninvasive Ventilation in the PICU: One Step Closer.

PMID- 28509738
TI  - It's Been a Hard Day's Night-What Determines Impact of Less Than 24/7 Rapid
      Response Systems?

PMID- 28509739
TI  - Fecal Micobiota Transplantation to Treat Sepsis of Unclear Etiology.

PMID- 28509740
TI  - Should We Prescribe Selective Serotonergic Reuptake Inhibitors/Serotonergic and
      Noradrenergic Reuptake Inhibitors in the ICU?

PMID- 28509741
TI  - To What Extent Does ABCDEF Bundle Improve Hospital Survival and Reduce Brain
      Dysfunction of 1,438 Patients With Mechanical Ventilation in Seven California
      Community Hospitals?

PMID- 28509742
TI  - The authors reply.

PMID- 28509743
TI  - The Role of Source Control in Septic Patients.

PMID- 28509744
TI  - Critical Care Echocardiography Guidelines: Strength in International Cooperation
      Regarding Terminology and Competency Standards.

PMID- 28509745
TI  - The authors reply.

PMID- 28509746
TI  - Guidelines for Family-Centered Care in Neuro-ICU Populations: Caveats for Routine
      Palliative Care.

PMID- 28509747
TI  - The authors reply.

PMID- 28509748
TI  - Iatrogenic Withdrawal Syndrome or Undiagnosed Delirium?

PMID- 28509749
TI  - The authors reply.

PMID- 28509750
TI  - Renin-Angiotensin-Aldosterone System Blockade Use in Sepsis Patients: Did It
      Impact Renal Outcomes?

PMID- 28509751
TI  - Optimal Cutoff Value for Lung Injury Prediction Score and Potential Confounders
      for Identifying the Risk of Developing Acute Respiratory Distress Syndrome.

PMID- 28509753
TI  - Physician-Assisted Suicide and Euthanasia Is Incompatible With Medicine: A
      Response From Medical Students.

PMID- 28509752
TI  - The authors reply.

PMID- 28509754
TI  - The authors reply.

PMID- 28509755
TI  - Ending Life in the ICU: The Vacuity of Sanctity.

PMID- 28509756
TI  - The authors reply.

PMID- 28509757
TI  - More Than a Prompt May be Needed to Improve Palliative Care Discussions for
      Hospitalized Patients.

PMID- 28509758
TI  - Post Hoc Analysis of Automated Early Warning System Alert Linked to End-of-Life
      Discussions-Is There a Racial Disparity in Effectiveness?

PMID- 28509759
TI  - The author replies.

PMID- 28509760
TI  - Global longitudinal strain predicts outcome after MitraClip implantation for
      secondary mitral regurgitation.
AB  - AIM: The aim of this study was to assess preoperative determinants, prevalence,
      and prognostic impact of left ventricular (LV) reverse remodeling (LVRR) in
      patients with secondary mitral regurgitation (SMR), undergoing MitraClip
      implantation (MCi). METHODS: From March 2012 to January 2015, a total of 41
      consecutive patients with moderate-to-severe SMR treated successfully with MCi
      were enrolled. All patients underwent clinical and echocardiographic follow-up
      after MCi. Global longitudinal strain (GLS) was obtained using two dimensional
      speckle tracking analysis. A reduction in LV end-systolic volume more than 10%
      compared with baseline was considered as a marker of LVRR. Patients were divided
      into two groups according to the presence or absence of LVRR. Cardiac events were
      defined as the occurrence of cardiac death, rehospitalization for worsening heart
      failure, and mitral valve surgery. RESULTS: On univariable analysis, EuroSCORE II
      and GLS were associated with LVRR. On multivariable logistic regression analysis,
      GLS was the only independent correlate of LVRR (P = 0.004). A receiver operating
      characteristic curve identified a cutoff value for GLS of -9.25% (P < 0.001)
      associated with LVRR, with a sensitivity and specificity of 81 and 74%,
      respectively. New York Heart Failure Association class more than 2 after MCi,
      absence of LVRR after MCi, and preoperative GLS more than -9.25% were
      significantly correlated with adverse cardiac events at long-term follow-up. On
      multivariable logistic regression analysis, GLS was the only independent
      predictor of composite adverse cardiac events at 2-year follow-up. CONCLUSION: A
      worse preoperative GLS predicts no LVRR and is associated with adverse long-term
      outcome after successful MCi for SMR.

PMID- 28509761
TI  - Dabigatran in nonvalvular atrial fibrillation: from clinical trials to real-life
      experience.
AB  - : Atrial fibrillation is the most common arrhythmia in over-midlife patients. In
      addition to systolic heart failure, cerebral thromboembolism represents the most
      dramatic complication of this rhythm disorder, contributing to morbidity and
      mortality. Traditionally, anticoagulation has been considered the main strategy
      in preventing stroke and systemic embolism in atrial fibrillation patients and
      vitamin K-dependent antagonists have been widely used in clinical practice.
      Recently, the development of direct oral anticoagulants has certainly improved
      the management of this disease, providing, for the first time, the opportunity to
      go beyond vitamin K-dependent antagonists limits. In the RE-LY trial, dabigatran
      150 mg twice daily was superior to warfarin in the prevention of stroke or
      systemic embolism and dabigatran 110 mg twice daily was noninferior. Both doses
      greatly reduced hemorrhagic stroke, and dabigatran 110 mg twice daily
      significantly reduced major bleeding compared with warfarin. Based on these
      results, dabigatran, a direct thrombin inhibitor, was the first direct oral
      anticoagulant to receive the regulatory approval for nonvalvular atrial
      fibrillation patients. To date, a specific reversal agent has just been approved
      as an antidote for this molecule. This review provides a summary of randomized
      trials, postmarket registries and specific clinical-settings summary on
      dabigatran in nonvalvular atrial fibrillation.

PMID- 28509762
TI  - Beetroot Juice Increases Human Muscle Force without Changing Ca2+-Handling
      Proteins.
AB  - : Dietary inorganic nitrate (NO3) supplementation improves skeletal muscle (SkM)
      contractile efficiency, and although rodent literature has suggested improvements
      in calcium handling or redox modifications as likely explanations, the direct
      mechanism of action in humans remains unknown. PURPOSE: This study aimed to
      examine the effects of 7 d of beetroot juice (BRJ) supplementation on SkM
      contractile characteristics and function. METHODS: Recreationally active males (n
      = 8) underwent transcutaneous electrical muscle stimulation of the vastus
      lateralis for the evaluation of contractile characteristics before and after 7 d
      of BRJ supplementation (280 mL.d, ~26 mmol NO3). An additional group of
      individuals (n = 8) followed the same supplementation protocol but underwent SkM
      biopsies pre- and post-supplementation for the determination of proteins
      associated with calcium handling via Western blotting, and the ratio of
      reduced/oxidized glutathione (GSH:GSSG), an indicator of cellular redox state,
      via high-performance liquid chromatography (HPLC). RESULTS: After
      supplementation, there was no change in maximal voluntary force production (602
      +/- 50 vs 596 +/- 56 N) or electrically induced tetanic contractions. By
      contrast, force production was increased at 10 Hz electrical stimulation (41.1%
      +/- 2.3% vs 37.6% +/- 2.4% of peak force, P < 0.05), as was peak twitch tension
      (164.0 +/- 12.5 vs 136.5 +/- 7.2 N, P < 0.01) and maximal rates of force
      development and relaxation (3582.8 +/- 382.3 vs 2575.7 +/- 196.2 and -2752.4 +/-
      423.9 vs -2104.4 +/- 249.0 N.s, respectively, P < 0.05). Despite these
      measurements implicating a change in calcium handling, the content of associated
      proteins (SERCA1a, SERCA2a, dihydropyradine receptor, ryanodine receptor, and
      calsequestrin) and the GSH:GSSG ratio were unaltered by BRJ. CONCLUSION: BRJ
      supplementation increases force production at low-stimulation frequencies;
      however, in human SkM, this is independent of changes in redox stress or the
      expression of protein targets associated with calcium handling.

PMID- 28509763
TI  - Achilles Tendon Load is Progressively Increased with Reductions in Walking Speed.
AB  - INTRODUCTION: Achilles tendon rehabilitation protocols commonly recommend a
      gradual increase in walking speed to progressively intensify tendon loading. This
      study used transmission-mode ultrasound to evaluate the influence of walking
      speed on loading of the human Achilles tendon in vivo. METHODS: Axial
      transmission speed of ultrasound was measured in the right Achilles tendon of 33
      adults (mean +/- SD: age, 29 +/- 3 yr; height, 1.725 +/- 0.069 m; weight, 71.4 +/
      19.9 kg) during unshod, steady-state treadmill walking at three speeds (slow,
      0.85 +/- 0.12 ms; preferred, 1.10 +/- 0.13 m.s; fast, 1.35 +/- 0.20 m.s). Ankle
      kinematics, spatiotemporal gait parameters and vertical ground reaction force
      were simultaneously recorded. Statistical comparisons were made using repeated
      measures ANOVA models. RESULTS: Increasing walking speed was associated with
      higher cadence, longer step length, shorter stance duration, greater ankle
      plantarflexion, higher vertical ground reaction force peaks, and a greater
      loading rate (P < 0.05). Maximum (F1,38 = 7.38, P < 0.05) and minimum (F1,46 =
      8.95, P < 0.05) ultrasound transmission velocities in the Achilles tendon were
      significantly lower (16-23 m.s) during the stance but not swing phase of gait,
      with each increase in walking speed. CONCLUSIONS: Despite higher vertical ground
      reaction forces and greater ankle plantarflexion, increasing walking speed
      resulted in a reduction in the axial transmission velocity of ultrasound in the
      Achilles tendon; indicating a speed-dependent reduction in tensile load within
      the triceps surae muscle-tendon unit during walking. These findings question the
      rationale for current progressive loading protocols involving the Achilles
      tendon, in which reduced walking speeds are advocated early in the course of
      treatment to lower Achilles tendon loads.

PMID- 28509764
TI  - Environmental and Physiological Factors Affect Football Head Impact Biomechanics.
AB  - PURPOSE: Recent anecdotal trends suggest a disproportionate number of head
      injuries in collegiate football players occur during preseason football camp. In
      warmer climates, this season also represents the highest risk for heat-related
      illness among collegiate football players. Because concussion and heat illnesses
      share many common symptoms, we need 1) to understand if environmental conditions,
      body temperature, and hydration status affect head impact biomechanics; and 2) to
      determine if an in-helmet thermistor could provide a valid measure of
      gastrointestinal temperature. METHODS: A prospective cohort of 18 Division I
      college football players (age, 21.1 +/- 1.4 yr; height, 187.7 +/- 6.6 cm; mass,
      114.5 +/- 23.4 kg). Data were collected during one control and three experimental
      sessions. During each session, the Head Impact Telemetry System recorded head
      impact biomechanics (linear acceleration, rotational acceleration, and severity
      profile) and in-helmet temperature. A wet bulb globe device recorded
      environmental conditions, and CorTempTM Ingestible Core Body Temperature Sensors
      recorded gastrointestinal temperature. RESULTS: Our findings suggest that linear
      acceleration (P = 0.57), rotational acceleration (P = 0.16), and Head Impact
      Technology severity profile (P = 0.33) are not influenced by environmental or
      physiological conditions. CONCLUSIONS: We did not find any single or combination
      of predictors for impact severity. Rotational acceleration was approaching
      significance between our early experimental sessions when compared with our
      control session. More research should be conducted to better understand if
      rotational accelerations are a component of impact magnitudes that are affected
      due to changes in environmental conditions, body temperature, and hydration
      status.

PMID- 28509766
TI  - Brown adipose tissue detected by PET/CT imaging is associated with less central
      obesity.
AB  - PURPOSE: This retrospective review was performed to determine whether patients
      with brown adipose tissue (BAT) detected by fluorine-18-fluorodeoxyglucose (F
      FDG) PET/computed tomography (CT) imaging have less central obesity than BMI
      matched control patients without detectable BAT. PATIENTS AND METHODS: Thirty
      seven adult oncology patients with F-FDG BAT uptake were retrospectively
      identified from PET/CT studies from 2011 to 2013. The control cohort consisted of
      74 adult oncology patients without detectable F-FDG BAT uptake matched for
      BMI/sex/season. Tissue fat content was estimated by CT density (Hounsfield units)
      with a subsequent noise removal step. Total fat and abdominal fat were
      calculated. An automated separation algorithm was utilized to determine the
      visceral fat and subcutaneous fat at the L4/L5 level. In addition, liver density
      was obtained from CT images. CT imaging was interpreted blinded to clinical
      information. RESULTS: There was no difference in total fat for the BAT cohort
      (34+/-15 l) compared with the controls (34+/-16 l) (P=0.96). The BAT cohort had
      lower abdominal fat to total fat ratio compared with the controls (0.28+/-0.05
      vs. 0.31+/-0.08, respectively; P=0.01). The BAT cohort had a lower visceral
      fat/(visceral fat+subcutaneous fat) ratio compared with the controls (0.30+/-0.10
      vs. 0.34+/-0.12, respectively; P=0.03). Patients with BAT had higher liver
      density, suggesting less liver fat, compared with the controls (51.3+/-7.5 vs.
      47.1+/-7.0 HU, P=0.003). CONCLUSION: The findings suggest that active BAT
      detected by F-FDG PET/CT is associated with less central obesity and liver fat.
      The presence of foci of BAT may be protective against features of the metabolic
      syndrome.

PMID- 28509770
TI  - Tumescent anaesthesia: its applications and well tolerated use in the out-of
      operating room setting.
AB  - PURPOSE OF REVIEW: Tumescent anaesthesia is a method of administering dilute
      local anaesthetic into the subcutaneous tissue. Many anaesthesiologists are
      unfamiliar with the technique, its applications and potential risks. RECENT
      FINDINGS: The maximum safe dose of lidocaine with epinephrine in tumescent
      anaesthesia for liposuction is probably between 35 and 55 mg/kg. Without
      liposuction, the maximum dose of lidocaine with epinephrine should be no more
      than 28 mg/kg. After tumescent infiltration for liposuction, serum lidocaine
      concentrations peak between 12 and 16 h after injection. When tumescent lidocaine
      without epinephrine is used for endovenous laser therapy, peak serum lidocaine
      concentrations are observed much earlier, between 1 and 2 h after injection. Slow
      administration of more dilute concentrations of local anaesthetic decreases the
      risk of local anaesthetic systemic toxicity. SUMMARY: Although appealing because
      of its ability to provide prolonged analgesia, high doses of local anaesthetic
      are frequently administered using the tumescent technique, and absorption of
      local anaesthetic from the subcutaneous tissue is variable. When caring for
      patients having procedures in which tumescent anaesthesia is used, the risk of
      local anaesthetic toxicity should be acknowledged and lipid emulsion should be
      available for prompt treatment if needed.

PMID- 28509765
TI  - Multicenter, real-life experience with checkpoint inhibitors and targeted therapy
      agents in advanced melanoma patients in Switzerland.
AB  - Metastatic melanoma is a highly aggressive disease. Recent progress in
      immunotherapy (IT) and targeted therapy (TT) has led to significant improvements
      in response and survival rates in metastatic melanoma patients. The current
      project aims to determine the benefit of the introduction of these new therapies
      in advanced melanoma across several regions of Switzerland. This is a
      retrospective multicenter analysis of 395 advanced melanoma patients treated with
      standard chemotherapy, checkpoint inhibitors, and kinase inhibitors from January
      2008 until December 2014. The 1-year survival was 69% (n=121) in patients treated
      with checkpoint inhibitors (IT), 50% in patients treated with TTs (n=113), 85% in
      the IT+TT group (n=66), and 38% in patients treated with standard chemotherapy
      (n=95). The median overall survival (mOS) from first systemic treatment in the
      entire study cohort was 16.9 months. mOS of patients treated either with
      checkpoint or kinase inhibitors (n=300, 14.6 months) between 2008 and 2014 was
      significantly improved (P<0.0001) compared with patients treated with standard
      chemotherapy in 2008-2009 (n=95, 7.4 months). mOS of 61 patients with brain
      metastases at stage IV was 8.1 versus 12.5 months for patients without at stage
      IV (n=334), therefore being significantly different (P=0.00065). Furthermore, a
      significant reduction in hospitalization duration compared with chemotherapy was
      noted. Treatment with checkpoint and kinase inhibitors beyond clinical trials
      significantly improves the mOS in real life and the results are consistent with
      published prospective trial data.

PMID- 28509771
TI  - Sedation for advanced procedures in the bronchoscopy suite: proceduralist or
      anesthesiologist?
AB  - PURPOSE OF REVIEW: This article focuses on the issue of sedation provided either
      by proceduralists or anesthesiologists for advanced bronchoscopy procedures. The
      relative merits of both approaches are presented. Current evidence from the
      literature and guideline recommendations relevant to this topic are reviewed.
      RECENT FINDINGS: In general, patient and proceduralist satisfaction as well as
      patient safety are increased when intravenous sedation is provided for advanced
      bronchoscopic procedures. However, guidelines by various societies remain vague
      on defining the appropriate level of care required when providing sedation for
      these procedures. In addition, targeted depth of sedation varies considerably
      among practitioners. While in some settings, nonanesthesiologist-administered
      propofol sedation has been proven safe; nevertheless, its use is controversial,
      especially in the bronchoscopy suite. SUMMARY: The role of the anesthesiologist
      in sedation for advanced bronchoscopy remains undefined. When deep sedation for
      prolonged interventional procedures is needed or when dealing with patients who
      have multiple comorbidities, an anesthesiologist should be involved.

PMID- 28509772
TI  - Safety of deep sedation in the endoscopy suite.
AB  - PURPOSE OF REVIEW: As the complexity of endoscopic procedures increases, the use
      of propofol and the desire for deep sedation are becoming more common in the
      endoscopy suite. This review explores sedation depth, agents used for sedation,
      recommended monitoring, and adverse event risks that occur during sedation for
      endoscopy. RECENT FINDINGS: The sedation provider for endoscopy varies by
      practice location and with regulatory requirements. As increasingly deep levels
      of sedation are used in this setting, the need for all providers to have training
      in the ability to rescue patients from sedation-related side effects is
      paramount. Propofol has an important role for prolonged and uncomfortable
      endoscopic interventions and has a strong safety record in the endoscopy suite.
      Vital signs monitoring is recommended during all endoscopy sedation, and there is
      emerging interest in advanced monitoring (e.g., capnography, processed
      electroencephalogram, respiratory monitoring) in this setting. The reported rate
      of adverse events during endoscopy sedation varies widely; however, advanced age
      and increasing American Society of Anesthesiologists physical status score are
      consistently associated with increased risk. Whether anesthesiologist
      administered sedation is safer than non-anesthesiologist-administered sedation
      remains controversial. SUMMARY: This review provides some guidance to providers
      who administer sedation in the endoscopy suite and is intended to improve the
      safety of patients. The recommendations are based on best available evidence and
      expert opinion.

PMID- 28509773
TI  - Perioperative management of antithrombotic therapies.
AB  - PURPOSE OF REVIEW: Perioperative coagulation management is becoming increasingly
      frequent in the daily routine of the anesthesiologist and with the plethora of
      new substances on the market also increasingly complex. The perioperative setting
      poses unique challenges requiring an individualized evaluation and management of
      antithrombotic therapy. This review shall summarize the newest developments in
      this domain. RECENT FINDINGS: New data in patients with atrial fibrillation have
      led to a paradigm change in the perioperative management of antithrombotics. The
      role of bridging therapy has been downgraded in the guidelines, which only
      foresee bridging in patients with high thromboembolic risk. Furthermore, direct
      oral anticoagulants are now a cornerstone in antithrombotic therapy, calling for
      specific perioperative management. The new reversal agents idarucizumab, and
      potentially in the future andexanet alfa and ciraparantag, will play an
      increasingly important role in the treatment of major bleeding in this group of
      patients. SUMMARY: With the new evidence and treatment options available,
      perioperative coagulation management is experiencing a Renaissance, opening many
      interesting new doors, but also presenting the clinician with new challenges.

PMID- 28509774
TI  - The role of the anaesthesiologist in air ambulance medicine.
AB  - PURPOSE OF REVIEW: The care administered on air ambulances has become increasing
      complex. This has led to a discussion among experts as to whether air ambulance
      travel should be manned by physicians. This review provides evidence in support
      of anaesthesiologists being the physician-leaders in air ambulance medicine,
      because of their training in advanced airway management, critical care, and
      resuscitation. RECENT FINDINGS: Successful prehospital care requires the ability
      to perform a complex set of advanced diagnostics and interventions. These include
      airway management, haemorrhage control, pain management, point-of-care
      diagnostics, complex interfacility transport, and advanced interventions. This
      skill set closely mirrors the training and expertise of anaesthesiologists.
      SUMMARY: There are few studies investigating the specific benefit of
      anaesthesiologists in air ambulance medicine. However, current evidence indicates
      that their presence does improve patient care and safety. Future studies on this
      topic should use evidence-based quality indicators and standardized data sets to
      seek answers to optimal staffing of air ambulance teams.

PMID- 28509775
TI  - Failed Vocalis Muscle Monitoring During Thyroid Surgery Resulting From Residual
      Muscle Relaxation.

PMID- 28509776
TI  - Hyperleukocytosis Complicated by Intracerebral Hemorrhage and Spurious Hypoxemia:
      A Case Report and Literature Review.
AB  - We present the management of a 15-year-old girl with acute myeloid leukemia who
      presented with massive hyperleukocytosis and neurological deficit due to
      intracerebral hemorrhage. Surgical intervention was considered but ultimately not
      undertaken because of the presence of massive hyperleukocytosis,
      thrombocytopenia, hypokalemia, and considerable discrepancy between the oxygen
      saturation values determined mechanically and by peripheral oximetry. Aggressive
      treatment of the hyperleukocytosis was immediately started, which improved the
      patient's overall condition and rendered surgical intervention unnecessary. This
      report shows that immediate treatment of massive hyperleukocytosis and critical
      interpretation of laboratory results in patients with hyperleukocytosis are
      warranted.

PMID- 28509777
TI  - Ultrasound-Guided Percutaneous Cryoneurolysis for Acute Pain Management: A Case
      Report.
AB  - We report 3 different cases in which ultrasound-guided percutaneous
      cryoneurolysis was performed to treat acute pain: 1 patient with refractory
      incisional pain after percutaneous nephrolithotomy; 1 patient with burns to the
      foot; and 1 patient with pain from iliac crest grafting. Acute pain associated
      with surgery or injury is a challenge to treat with local anesthetic-based
      regional anesthesia techniques when the anticipated pain duration exceeds a few
      days. Cryoneurolysis is an alternative analgesic method that utilizes extremely
      cold temperatures to reversibly ablate peripheral nerves and is potentially a
      novel method for acute pain management.

PMID- 28509778
TI  - Multiple Anesthetic Drug Sensitization in a Hairdresser With Previous Immediate
      Type Hypersensitivity to Penicillin: A Case Report.
AB  - Risk factors for intraoperative immediate-type hypersensitivity reactions may
      require allergological evaluation. We report the case of a hairdresser with a
      positive history of penicillin hypersensitivity and anaphylactic shock during
      previous general anesthesia, whose in vivo and in vitro allergy tests were
      positive for neuromuscular blocking agents, opioids, and midazolam. Immediate
      type hypersensitivity reactions to antibiotics and professional exposure to
      hairdressing products might induce simultaneous cross-sensitization to multiple
      drugs that are commonly used during general anesthesia.

PMID- 28509779
TI  - Gas Embolism During Hysteroscopic Surgery?: Three Cases and a Literature Review.
AB  - During a period of 1 month, 3 episodes of probable or actual venous air embolism
      occurred during hysteroscopic surgery. All patients developed the same symptoms
      of ventilatory and hemodynamic decompensation, beginning with a reduction in end
      tidal carbon dioxide, arterial desaturation, and cyanosis on the upper trunk, and
      rapidly progressed to hypotension and 2 cardiac arrests. While entrainment of
      some air is common during hysteroscopy, life-threatening embolism is a rare but
      serious complication for which an anesthetist needs to be vigilant and prepared.
      If even a small drop in end-tidal carbon dioxide occurs, venous air embolism
      should be suspected and the operation should be discontinued.

PMID- 28509780
TI  - Hypnosis and Axillary Compartment Block for Breast Cancer Surgery: A Case Report.
AB  - Hypnosis has been proven to be a powerful tool in the management of anxiety and
      pain. It allows for an increase of pain threshold, which can reach the level of
      surgical analgesia. Recently injection of local anesthetics around the serratus
      muscle has been presented as an alternative to paravertebral block for cancer
      breast surgery. We report the successful use of hypnosis in combination with an
      axillary compartment block for lumpectomy and axillary lymph node dissection.

PMID- 28509781
TI  - Correction of Severe Coagulopathy and Hyperfibrinolysis by Tranexamic Acid and
      Recombinant Factor VIIa in a Cirrhotic Patient After Trauma: A Case Report.
AB  - Coagulopathy induced by trauma or cirrhosis is a well-recognized entity.
      Viscoelastic testing has been used in either condition for goal-directed
      transfusion and detection of fibrinolysis since conventional coagulation tests do
      not correlate with clinical risk of bleeding. Hemostatic resuscitation may not be
      adequate for a trauma patient with liver disease due to complex alterations in
      coagulation systems and occasionally require adjuvant therapy. We report a case
      of trauma-induced coagulopathy presenting as severe hyperfibrinolysis in a
      cirrhotic patient who was refractory to hemostatic resuscitation but was rapidly
      corrected by the administration of tranexamic acid and recombinant Factor VIIa.

PMID- 28509782
TI  - An update on the impact of food allergy on anxiety and quality of life.
AB  - PURPOSE OF REVIEW: Food allergies have become more common, and management
      involves dietary avoidance that can impair quality of life. Patients and families
      must manage the daily risk of anaphylaxis at each meal. The purpose of this
      review is to describe the impact of food allergies on quality of life and to
      provide an update on new developments in food allergy management, particularly
      peanut allergy. RECENT FINDINGS: Food allergy requires careful avoidance of
      common and ubiquitous dietary allergens. Living with food allergy is associated
      with annual economic costs in excess of $4000 per child, in addition to risks of
      anxiety and depressive symptoms. An expert panel sponsored by the 2017 National
      Institute of Allergy and Infectious Diseases published addendum guidelines for
      the prevention of peanut allergy, which suggest three separate approaches to
      peanut protein introduction for infants at various levels of risk. SUMMARY:
      Clinicians must be aware of underappreciated burdens faced by children and
      families with food allergies. Management involves a partnership between primary
      and specialty care. Mitigation strategies to improve quality of life for patients
      include efforts to avoid overdiagnosis in synergy with balanced counseling about
      the risks of food allergies. Experimental food allergen desensitization can
      improve quality of life but remains investigational at this time. For patients
      with significant anxiety, interdisciplinary management involving professional
      counseling may be helpful. Risk stratification and early introduction of peanut
      protein can help prevent the development of peanut allergy.

PMID- 28509783
TI  - The evaluation of adolescent chest pain: a screening ECG or PSC-17?
AB  - PURPOSE OF REVIEW: The present review offers an update on entities presenting as
      chest pain in the adolescent population. It discusses recently proposed tools and
      shared mental models used in primary and urgent care settings to evaluate chest
      pain, and their focus on identifying life-threatening processes. We consider
      whether the current practice may be improved by accounting for the increasingly
      recognized non-life-threatening causes of adolescent chest pain. RECENT FINDINGS:
      The present experiences and behaviors of adolescents have added new causes of
      chest pain to the work-up of this disquieting chief complaint. The initial
      approach to adolescent chest pain has classically focused on ruling out life
      threatening entities, and current diagnostic algorithms offer systematic
      approaches with similar emphases. A growing body of literature on the nonlife
      threatening causes of adolescent chest pain, often categorized as idiopathic,
      suggests a need to reevaluate our practice. SUMMARY: Adolescent chest pain is
      most often noncardiac and non-life threatening in nature, yet current diagnostic
      algorithms and evaluations emphasize identifying the exceptional case of cardiac
      chest pain. Familiarizing ourselves with the more common causes of chest pain and
      with our present approach to the evaluation of this particular chief complaint,
      may help us to better counsel our patients and avoid unnecessary use of valuable
      resources.

PMID- 28509784
TI  - Pharmacotherapy options for pediatric diabetes.
AB  - PURPOSE OF REVIEW: Type 1 diabetes (T1D) and type 2 diabetes (T2D) are frequent
      conditions during childhood and adolescence. The present review offers an update
      on current available treatment strategies for T1D and T2D approved for use in
      children and adolescents. RECENT FINDINGS: Insulin remains the main and essential
      therapeutic strategy in youth with T1D. A second generation of insulin analogues
      is being evaluated and could help in improving glycemic control. Over the last
      decades advances in technology have allowed the implementation of insulin pump
      therapy and continuous glucose monitoring, and are now leading the way towards
      the development of an artificial pancreas or closed loop system.Treatment of T2D
      is based on lifestyle interventions and metformin as the first-line drug to be
      used. Little evidence is available for other oral hypoglycemic drugs, currently
      used in adults. SUMMARY: Although much progress has been made in the field of
      diabetes management, there are still several unmet goals. One of the main issues
      is to develop a system allowing more physiological insulin coverage. For both T1D
      and T2D, there is a strong need of new drugs to be used alone or in combination,
      mainly in patients struggling to achieve good glycemic control.

PMID- 28509785
TI  - Inflammatory bowel disease treatment in Eastern Europe: current status,
      challenges and needs.
AB  - PURPOSE OF REVIEW: To analyze the available studies of course, diagnosis and
      treatment of Inflammatory bowel disease (IBD) in Eastern Europe. RECENT FINDINGS:
      According to published data, full epidemiological studies were conducted only in
      Czech Republic, Estonia, Hungary and Romania. Russia was recently included in the
      EpiCom study, although only Moscow region data were provided. SUMMARY: We
      summarize previously published and unpublished data on the epidemiology, IBD
      diagnosis and treatment in Eastern Europe. In addition, changes during several
      years are presented. These data show that IBD epidemiology in Eastern Europe
      corresponds to the previously known patterns, and that the quality of IBD health
      care has improved in the last several years.

PMID- 28509786
TI  - IgG4-related disease of the biliary tract and pancreas: clinical and experimental
      advances.
AB  - PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is an immune-mediated disease
      of unknown cause. It predominantly affects the biliary tract [IgG4-associated
      cholangitis (IAC)] and pancreas [autoimmune pancreatitis (AIP)] of mostly elderly
      men. Accurate diagnostic tests are lacking. Patients benefit from predniso(lo)ne
      treatment. However, disease relapse is often seen. This review will address
      pathophysiological aspects and advances in diagnostic and therapeutic strategies.
      RECENT FINDINGS: The role of IgG1 and IgG4 in the pathophysiology of IgG4-RD was
      studied in mice which showed more intense organ damage of pancreas and salivary
      glands when IgG1 rather than IgG4 of patients with IgG4-RD was injected.
      Coadministration of IgG1+IgG4 led to dampening of IgG1-mediated injury supporting
      the view that IgG4 exerts immune-dampening effects. IgG4+ B-cell receptor clones
      identified by next-generation sequencing and the IgG4/IgG RNA ratio in human
      blood assessed by quantitative PCR were able to accurately distinguish IAC/AIP
      from primary sclerosing cholangitis or pancreatobiliary malignancies. Long-term
      treatment with low-dose prednisolone was safe and reduced the number of flare-ups
      in patients with AIP. SUMMARY: Early diagnosis by a novel accurate and easy-to
      use qPCR test may prevent life-threatening complications, unnecessary
      interventions and fatal course because of misdiagnosis. Prednisolone treatment
      remains the standard of care in patients with IgG4-RD.

PMID- 28509793
TI  - Remifentanil Dosing at Extremes of Body Weight.

PMID- 28509794
TI  - An Allometric Model of Remifentanil Pharmacokinetics and Pharmacodynamics.
AB  - BACKGROUND: Pharmacokinetic and pharmacodynamic models are used to predict and
      explore drug infusion schemes and their resulting concentration profiles for
      clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic
      model for remifentanil that is accurate in patients with a wide range of age and
      weight. METHODS: Remifentanil pharmacokinetic data were obtained from three
      previously published studies of adults and children, one of which also contained
      pharmacodynamic data from adults. NONMEM was used to estimate allometrically
      scaled compartmental pharmacokinetic and pharmacodynamic models. Weight, age,
      height, sex, and body mass index were explored as covariates. Predictive
      performance was measured across young children, children, young adults, middle
      aged, and elderly. RESULTS: Overall, 2,634 remifentanil arterial concentration
      and 3,989 spectral-edge frequency observations from 131 individuals (55 male, 76
      female) were analyzed. Age range was 5 days to 85 yr, weight range was 2.5 to 106
      kg, and height range was 49 to 193 cm. The final pharmacokinetic model uses age,
      weight, and sex as covariates. Parameter estimates for a 35-yr-old, 70-kg male
      (reference individual) are: V1, 5.81 l; V2, 8.82 l; V3, 5.03 l; CL, 2.58 l/min;
      Q2, 1.72 l/min; and Q3, 0.124 l/min. Parameters mostly increased with fat-free
      mass and decreased with age. The pharmacodynamic model effect compartment rate
      constant (ke0) was 1.09 per minute (reference individual), which decreased with
      age. CONCLUSIONS: We developed a pharmacokinetic-pharmacodynamic model to predict
      remifentanil concentration and effect for a wide range of patient ages and
      weights. Performance exceeded the Minto model over a wide age and weight range.

PMID- 28509796
TI  - Disposition of Remifentanil in Obesity: A New Pharmacokinetic Model Incorporating
      the Influence of Body Mass.
AB  - BACKGROUND: The influence of obesity on the pharmacokinetic (PK) behavior of
      remifentanil is incompletely understood. The aim of the current investigation was
      to develop a new population PK model for remifentanil that would adequately
      characterize the influence of body weight (among other covariates, e.g., age) on
      the disposition of remifentanil in the general adult population. We hypothesized
      that age and various indices of body mass would be important covariates in the
      new model. METHODS: Nine previously published data sets containing 4,455 blood
      concentration measurements from 229 subjects were merged. A new PK model was
      built using nonlinear mixed-effects modeling. Satisfactory model performance was
      assessed graphically and numerically; an internal, boot-strapping validation
      procedure was performed to determine the CIs of the model. RESULTS: Body weight,
      fat-free body mass, and age (but not body mass index) exhibited significant
      covariate effects on certain three-compartment model parameters. Visual and
      numerical assessments of model performance were satisfactory. The bootstrap
      procedure showed satisfactory CIs on all of the model parameters. CONCLUSIONS: A
      new model estimated from a large, diverse data set provides the PK foundation for
      remifentanil dosing calculations in adult obese and elderly patients. It is
      suitable for use in target-controlled infusion systems and pharmacologic
      simulation.

PMID- 28509801
TI  - Images in Anesthesiology: Anomalous Single Coronary Artery from the Pulmonary
      Artery.

PMID- 28509802
TI  - Measurement of Patient Outcomes Important.

PMID- 28509803
TI  - In Reply.

PMID- 28509804
TI  - Video Laryngoscopes and Best Rescue Strategy for Unexpected Difficult Airways: Do
      Not Forget a Combined Approach with Flexible Bronchoscopy!

PMID- 28509805
TI  - In Reply.

PMID- 28509806
TI  - Advances in management of hepatocellular carcinoma.
AB  - PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of
      death by cancer worldwide due to a dismal prognosis. The aim of this review is to
      summarize the main advances in the pathophysiology and management of HCC. RECENT
      FINDINGS: Genomic analysis has recently delineated the key signaling pathways
      aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/beta
      catenin, epigenetic modifier, oxidative stress etc.). Major advances in the
      clinical care of patients with HCC are helping to refine the diagnosis algorithm
      and tumor staging. Extension of criteria for liver transplantation, but also for
      liver resection and percutaneous ablation, aims to increase the number of
      patients being treated in a curative attempt. Moreover, radioembolization is a
      competitor for transarterial chemoembolization in Barcelona clinic liver cancer B
      patients, and sorafenib in Barcelona clinic liver cancer C with tumor portal
      thrombosis. In advanced HCC, sorafenib is the standard of first-line care and
      regorafenib as a second line. SUMMARY: New concepts on liver resection,
      percutaneous ablation or liver transplantation aim to extend the numbers of
      patients treated for HCC in curative attempts. Moreover, immunotherapy (anti
      death protein 1) and biotherapy adapted to tumor biology seem promising and are
      currently being tested in advanced stages.

PMID- 28509807
TI  - Treatment of retroperitoneal sarcoma: current standards and new developments.
AB  - PURPOSE OF REVIEW: Retroperitoneal sarcomas are rare tumors and with complex
      treatment. In this manuscript we give an overview of current standards in
      treatment of this disease and discuss new developments. RECENT FINDINGS: Surgery
      with complete resection of the primary tumor is still the only curative modality.
      The role of preoperative radiotherapy is not clear and is currently being
      investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard
      of care but can be considered occasionally when complete resection is uncertain.
      Local and distant recurrent disease carries a dismal prognosis, although long
      term survival can be achieved. Liposarcomas tend to recur locally, whereas
      distant recurrences are more often seen in leiomyosarcoma and other subtypes.
      Outcome improves when patients are treated in high volume sarcoma centers. In the
      metastatic setting, newer systemic agents have recently been approved. SUMMARY:
      Treatment of retroperitoneal sarcomas is complex and all patients should be
      treated in multidisciplinary sarcoma centers. Increasing international
      collaboration of expert centers in sharing expertise and performing clinical
      trials might lead to better treatment and improved survival.

PMID- 28509808
TI  - Implementing patient information for gynae-oncology patients at a tertiary
      referral health service.
AB  - AIM: To ensure that gynae-oncology surgical patients receive relevant written
      information, in their preferred format, and at a time that suits them, according
      to the best available evidence. METHODS: This project utilized an audit and
      feedback design and was conducted over a 9-month period from August 2015 to May
      2016. Twenty-nine patients were audited prior to two strategies being
      implemented. The first strategy was a standardized e-mail letter to all patients
      (containing links to surgical information, cancer support websites and a short
      video introducing hospital staff, and the second was a discharge information
      sheet detailing wound care, signs of complications, actions to take and follow-up
      instructions. Thirty patients were audited post-implementation to evaluate the
      success of these strategies. RESULTS: There were significant increases in the
      number of patients who said they received written information on their diagnosis,
      surgery and potential complications at initial consultation and a significant
      increase in the number of patients who said they were provided with written
      follow-up information on discharge. Pre-audit, 83% of patients stated they would
      like to receive a list of reliable websites to access and post-audit, 89% of
      patients stated they found the websites provided were useful. DISCUSSION:
      Although gynae-oncology surgical patients did previously receive relevant verbal
      information, little or no written information was provided. The pre
      implementation audit provided insight into the information these patients
      required. The e-mail was generally well received by patients; however; there was
      a minority who did not have internet access and therefore a paper version was
      provided. CONCLUSION: This project identified deficits in the provision of
      written information for surgical gynae-oncology patients. Two strategies were
      implemented to address this deficit with positive results in the number of
      patients receiving written information; however, further investigation is needed
      to establish patient satisfaction with this information.

PMID- 28509810
TI  - The triple C (consultation, collaboration and consolidation) model: a way forward
      to sustainability of evidence into practice.

PMID- 28509809
TI  - Evidence-based practice among health professionals in hospitals of Northwest
      Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Evidence-based practice (EBP) is a problem-solving approach to
      patient care based on the best available and valid evidence. It is accentuated to
      increase the quality of care and patient safety. EBP in clinical service is low
      in developing countries including Ethiopia. This study aimed at assessing EBP and
      associated factors among health professionals in North Gondar Administrative Zone
      hospitals, Northwest Ethiopia. METHODS: Institution-based cross-sectional study
      was carried out from March to May 2015 in three hospitals in North Gondar Zone. A
      stratified simple random sampling technique was used to select 438 respondents.
      Trained data collectors collected data using a pre-tested, structured and self
      administered questionnaire. The questionnaire included sociodemographic
      characteristics, level of knowledge, attitude and organizational factors. Data
      were entered using Epi Info version 7.0 and analysed using SPSS version 20.0.
      Bivariate and multivariable logistic regression analyses were undertaken to
      identify the associated factors. RESULTS: In total, 431 returned questionnaires
      were valid for the analysis making a response rate of 98.4%. Almost half, 53%
      (228) of study participants utilized EBP. EBP utilization was significantly
      associated with knowledge [adjusted odds ratio (AOR): 1.612, 95% confidence
      interval (CI) = (1.06-2.45)], Internet access [AOR: 1.831, 95% CI = (1.191
      2.816)], training [AOR: 1.906, 95% CI (1.223-2.97)], and availability of enough
      time to apply EBP [AOR: 1.698, 95% CI = (1.122-2.57)]. CONCLUSION: This study
      depicts EBP utilization was insufficient. We observed that knowledge of EBP,
      training, Internet access and availability of time were significantly associated
      with utilizing EBP. Improving facilities Internet access, giving more time for
      EBP, and training health professionals about search strategies would improve EBP.

PMID- 28509811
TI  - Implementation of a new method to track propofol in an endoscopy unit.
AB  - AIM: Propofol is a widely used anesthesia induction agent and is easily
      accessible in most healthcare facilities. Unlike regulated or schedule drugs,
      propofol is inconsistently tracked, leading to inaccurate inventories, incorrect
      billing, and unrecognized diversion. The goal of this project was to implement a
      new method of tracking propofol in a single setting, with the aim of accounting
      for 100% of the drug. METHODS: For two, 2-week observation periods, data were
      extracted from an automated medication management system or pharmacy inventory
      system, anesthesia records, and pharmacy billing sheets for cases in a
      Gastrointestinal (GI) Endoscopy Unit, and compared pre-implementation and post
      implementation of a new tracking and accounting protocol. Variables included
      amount of propofol inventoried, dispensed, administered, returned, billed,
      wasted, and missing. RESULTS: Pre-implementation (n = 300), 10% cases had no
      record of propofol removal from the automated medication system. Of the 90% that
      did, 25% had an amount signed out that did not match the amount administered.
      Thirty-one percent of all propofol was unaccounted for during this 2-week period.
      Furthermore, 19.7% of cases did not have a billing form located. Post
      implementation of the process change, unaccounted for propofol decreased to 26%
      of all cases (P = ns). The percentage of missing billing forms decreased from
      19.7 to 5.8% (P = 0.00). CONCLUSION: Data suggest notable amounts of propofol
      were unaccounted for and not billed for in the GI Endoscopy Unit prior to the
      protocol change. Post-protocol change data reveal modest improved accounting of
      the medication and significant cost-capture. Improvements may enhance inventory
      reconciliation, availability of drug stock, and potentially result in a decreased
      risk of unrecognized diversion.

PMID- 28509812
TI  - Ospemifene's effects on lipids and coagulation factors: a post hoc analysis of
      phase 2 and 3 clinical trial data.
AB  - OBJECTIVE: To evaluate the effect of ospemifene 60 mg on the lipid and
      coagulation parameters of postmenopausal women using data from five phase 2 and 3
      clinical trials. METHODS: Data for lipids and coagulation factors for 2,166
      postmenopausal women were pooled from five randomized, placebo-controlled
      studies. Lipid and coagulation parameters included in this analysis were total
      cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL),
      triglycerides, activated partial thromboplastin time (aPTT), fibrinogen,
      antithrombin antigen, protein C Ag, and protein S Ag free. RESULTS: Mean percent
      changes in HDL and LDL were significantly greater with ospemifene versus placebo
      at month 3 (HDL: 4.4% vs 0.2%; LDL: -5.2% vs 2.4%), month 6 (HDL: 5.1% vs 1.5%;
      LDL: -6.7% vs 2.4%), and month 12 (HDL: 2.3% vs -1.9%; LDL: -7.0% vs -2.1%; P <
      0.05, for all comparisons). Ospemifene significantly reduced total cholesterol at
      6 months (-1.8% vs 1.6%; P = 0.0345 versus placebo), and changes in triglycerides
      with ospemifene were similar to placebo at all three time points. In subgroup
      analyses based on age, body mass index, and baseline triglyceride level,
      ospemifene increased HDL and decreased LDL, but had no significant effect on
      total cholesterol and triglycerides relative to placebo. Ospemifene significantly
      improved fibrinogen and protein C antigen levels relative to placebo at months 3
      (-8.7% vs -0.8% and -2.7% vs 0.5%, respectively), 6 (-6.0% vs 6.7% and -3.6 vs
      8.0%), and 12 (-8.7% vs 7.3% and -4.5% vs 6.6%; P < 0.01, for all). The levels of
      all coagulation factors remained within the normal range throughout the studies.
      CONCLUSION: Ospemifene 60 mg does not have a detrimental effect on lipid and
      coagulation parameters of postmenopausal women with up to 12 months of use.

PMID- 28509813
TI  - Effect of Foeniculum vulgare Mill. (fennel) on menopausal symptoms in
      postmenopausal women: a randomized, triple-blind, placebo-controlled trial.
AB  - OBJECTIVE: Preliminary data suggest that Foeniculum vulgare (fennel) can be an
      effective treatment for menopausal symptoms. This trial was designed to assess
      the efficacy of fennel in the management of menopausal symptoms in postmenopausal
      women. METHODS: In this triple-blind, placebo-controlled trial, 90 postmenopausal
      women aged 45 to 60 years in Tehran were randomly assigned to treatment (n = 45)
      or placebo (n = 45) groups. The participants received 8 weeks of treatment with
      soft capsules containing 100 mg fennel or a placebo (2 per day for each group).
      The participants were followed for 2 weeks postintervention to assess the
      continuance of the effect of intervention. The Menopause Rating Scale (MRS)
      questionnaire was used to assess changes in menopausal symptoms at baseline and
      at 4, 8, and 10 weeks after onset of intervention. RESULTS: The groups recorded
      similar mean scores on the MRS questionnaire before intervention. After
      intervention, the treatment group showed a significant decrease in the mean MRS
      score. The results of the Friedman test showed significant differences between
      the mean score at baseline and those at 4, 8, and 10 weeks after onset of
      intervention in the treatment group (P < 0.001), whereas there were no
      significant differences in the placebo group. When the fennel and the placebo
      groups were compared, the independent t test showed significant differences in
      mean scores between groups at 4, 8, and 10 weeks (2 weeks postintervention; P <
      0.001). CONCLUSIONS: Fennel is an effective and safe treatment to reduce
      menopausal symptoms in postmenopausal women without serious side effects. More
      clinical trials with larger populations are required to confirm this result.

PMID- 28509815
TI  - Serum iron concentration is associated with subcortical deep gray matter iron
      levels in multiple sclerosis patients.
AB  - Iron deposition has been noted widely in the subcortical deep gray matter (SDGM)
      of multiple sclerosis (MS) patients. Recent evidence suggests that serum iron may
      cross the blood-brain barrier and might be associated with SDGM iron deposition.
      The aim of the current study was to assess whether an iron-sensitive MRI measure
      is related to serum iron concentrations. This was a retrospective, cross
      sectional study of 22 MS patients and 24 healthy controls (HCs), group matched
      for age and sex. Participants were imaged on a 1.5-T MRI scanner. High-resolution
      T1-weighted images and susceptibility-weighted images were acquired for assessing
      SDGM volumes and iron deposition within the SDGM, respectively. All participants
      also had blood drawn for the measurement of serum iron concentrations. MS and HC
      groups were compared with respect to SDGM tissue volumes and iron content.
      Partial correlations, controlling for age, sex, and structural volume, were used
      to assess the relationship between serum iron and SDGM iron content. MS patients
      presented with significantly smaller SDGM tissue volumes of the caudate, globus
      pallidus, putamen, and thalamus (all P<=0.0001). With respect to HCs, increased
      iron content was observed for MS patients in the globus pallidus (P=0.009) only.
      In MS patients only, there was a significant relationship between serum iron and
      putaminal iron volume (partial r=0.449, P=0.041), whereas trends were evidenced
      for the caudate (partial r=0.396, P=0.078) and the globus pallidus (partial
      r=0.410, P=0.065). Serum iron content in MS patients may be related to SDGM iron
      content. These results warrant confirmation in a larger study of MS patients.

PMID- 28509814
TI  - Validity, cut-points, and minimally important differences for two hot flash
      related daily interference scales.
AB  - OBJECTIVES: To conduct psychometric analyses to condense the Hot Flash-Related
      Daily Interference Scale (HFRDIS) into a shorter form termed the Hot Flash
      Interference (HFI) scale; evaluate cut-points for both scales; and establish
      minimally important differences (MIDs) for both scales. METHODS: We analyzed
      baseline and postrandomization patient-reported data pooled across three
      randomized trials aimed at reducing vasomotor symptoms (VMS) in 899 midlife
      women. Trials were conducted across five MsFLASH clinical sites between July 2009
      and October 2012. We eliminated HFRDIS items based on experts' content validity
      ratings and confirmatory factor analysis, and evaluated cut-points and
      established MIDs by mapping HFRDIS and HFI to other measures. RESULTS: The three
      item HFI (interference with sleep, mood, and concentration) demonstrated strong
      internal consistency (alphas of 0.830 and 0.856), showed good fit to the
      unidimensional "hot flash interference factor," and strong convergent validity
      with HFRDIS scores, diary VMS, and menopausal quality of life. For both scales,
      cut-points of mild (0-3.9), moderate (4-6.9), and severe (7-10) interference were
      associated with increasing diary VMS ratings, sleep, and anxiety. The average MID
      was 1.66 for the HFRDIS and 2.34 for the HFI. CONCLUSIONS: The HFI is a brief
      assessment of VMS interference and will be useful in busy clinics to standardize
      VMS assessment or in research studies where response burden may be an issue. The
      scale cut-points and MIDs should prove useful in targeting those most in need of
      treatment, monitoring treatment response, and interpreting existing and future
      research findings.

PMID- 28509816
TI  - Variations in Health Insurance Policies Regarding Biologic Therapy Use in
      Inflammatory Bowel Disease.
AB  - BACKGROUND: The American Gastroenterological Association (AGA) has developed
      guidelines for the management of ulcerative colitis and Crohn's disease (CD)
      recommending anti-TNF therapy in moderate-severe disease. However, which drug is
      used is often dictated by insurance company policies. We sought to determine the
      insurance policy requirements prior to approval of biologic therapies. METHODS:
      Using the National Association of Insurance Commissioners report of the top 125
      insurance companies by market share in 2014, we reviewed the first 50 that had
      online policies regarding anti-TNF and vedolizumab available. Policies were
      reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and
      for compliance with the current AGA clinical pathway recommendations. RESULTS:
      Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis
      pathway and require step-wise drug failure before approval of an anti-TNF. Only
      11% of the policies allowed starting vedolizumab without initial failures of an
      anti-TNF agent, and 21% required the failure of two or more anti-TNF agents.
      Ninety percent of the policies are inconsistent with AGA CD pathway and require
      step-wise drug failure before approval of an anti-TNF. Seventy-four percent
      allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight
      percent required failing of at least two or more drugs before starting anti-TNF.
      Only 8% policies allowed starting vedolizumab without initial failures of an anti
      TNF agent, and 28% required the failure of two anti-TNF agents. CONCLUSIONS: The
      majority of the policies reviewed fail to adhere to the current AGA pathway
      recommendations for ulcerative colitis and CD. Further interventions are needed
      to better align policies with optimal evidence-based drug therapy.

PMID- 28509818
TI  - Commentary on Variations in Health Insurance Policies Regarding Biological
      Therapy Use in IBD and a Modified Delphi Process for the Development of Choosing
      Wisely for IBD.

PMID- 28509817
TI  - Modified Delphi Process for the Development of Choosing Wisely for Inflammatory
      Bowel Disease.
AB  - BACKGROUND AND AIMS: The prevalence and incidence of inflammatory bowel disease
      (IBD) in North America is among the highest in the world and imparts substantial
      direct and indirect medical costs. The Choosing Wisely Campaign was launched in
      wide variety of medical specialties and disciplines to reduce unnecessary or
      harmful tests or treatment interventions. METHODS: The Choosing Wisely list for
      IBD was developed by the Canadian IBD Network for Research and Growth in Quality
      Improvement (CINERGI) in collaboration with Crohn's and Colitis Canada (CCC) and
      the Canadian Association of Gastroenterology (CAG). Using a modified Delphi
      process, 5 recommendations were selected from an initial list of 30 statements at
      a face-to-face consensus meeting. RESULTS: The 5 things physicians and patients
      should question: (1) Don't use steroids (e.g., prednisone) for maintenance
      therapy in IBD; (2) Don't use opioids long-term to manage abdominal pain in
      inflammatory bowel disease (IBD); (3) Don't unnecessarily prolong the course of
      intravenous corticosteroids in patients with acute severe ulcerative colitis (UC)
      in the absence of clinical response; (4) Don't initiate or escalate long-term
      medical therapies for the treatment of IBD based only on symptoms; and (5) Don't
      use abdominal computed tomography (CT) scan to assess IBD in the acute setting
      unless there is suspicion of a complication (obstruction, perforation, abscess)
      or a non-IBD etiology for abdominal symptoms. CONCLUSIONS: The Choosing Wisely
      recommendations will foster patient-physician discussions to optimize IBD
      therapy, reduce adverse effects from testing and treatment, and reduce medical
      expenditure.

PMID- 28509819
TI  - Cortical and Physical Function after Mild Traumatic Brain Injury.
AB  - PURPOSE: The aim of this study was to prospectively examine the association
      between intracortical inhibition and functional recovery after mild traumatic
      brain injury (mTBI). METHODS: Twenty individuals with mTBI and 20 matched control
      participants were assessed using transcranial magnetic stimulation, the
      Attentional Network Test, and gait analysis. Hierarchical linear modeling was
      used to longitudinally examine potential differences between groups and
      relationships in the pattern of recovery in cortical silent period (CSP)
      duration, cognitive reaction time, and single- and dual-task walking speeds
      across five testing time points. Individuals with mTBI were assessed within 72 h
      of injury, and again at 1 wk, 2 wk, 1 month, and 2 months postinjury. After
      initial testing, control participants followed a similar timeline. RESULTS: At
      the 72-h time point, the group with mTBI had longer reaction time (b = -91.76, P
      = 0.01), similar single-task walking speed (b = 0.055, P = 0.10), and slower dual
      task walking speed (b = 0.10, P = 0.012) compared with control participants. The
      CSP duration also tended to be longer in individuals with mTBI than controls at
      the 72-h time point (b = -16.34, P = 0.062). The change is CSP duration over time
      was not significantly associated with the change in reaction time (b = -0.19, P =
      0.47), single-task walking speed (b = 0.0001, P = 0.53), or dual-task walking
      speed (b < 0.001, P = 0.68). CONCLUSION: Although cognitive and motor functions
      were significantly impaired in the mTBI group acutely after injury, levels of
      intracortical inhibition were not associated with recovery in either functional
      domain.

PMID- 28509820
TI  - Impact of Preoperative Opioid Use on Total Knee Arthroplasty Outcomes.
AB  - BACKGROUND: There is growing concern about the use of opioids prior to total knee
      arthroplasty (TKA), and research has suggested that preoperative opioid use may
      lead to worse pain outcomes following surgery. We evaluated the pain relief
      achieved by TKA in patients who had and those who had not used opioids use before
      the procedure. METHODS: We augmented data from a prospective cohort study of TKA
      outcomes with opioid-use data abstracted from medical records. We collected
      patient-reported outcomes and demographic data before and 6 months after TKA. We
      used the Pain Catastrophizing Scale and the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) to quantify the pain experiences of
      patients treated with TKA who had had a baseline score of >=20 on the WOMAC pain
      scale (a 0 to 100-point scale, with 100 being the worst score), who provided
      follow-up data, and who had not had another surgical procedure within the 2 years
      prior to TKA. We built a propensity score for preoperative opioid use based on
      the Pain Catastrophizing Scale score, comorbidities, and baseline pain. We used a
      general linear model, adjusting for the propensity score and baseline pain, to
      compare the change in the WOMAC pain score 6 months after TKA between persons who
      had and those who had not used opioids before TKA. RESULTS: The cohort included
      156 patients with a mean age of 65.7 years (standard deviation [SD] = 8.2 years)
      and a mean body mass index (BMI) of 31.1 kg/m (SD = 6.1 kg/m); 62.2% were female.
      Preoperatively, 36 patients (23%) had had at least 1 opioid prescription. The
      mean baseline WOMAC pain score was 43.0 points (SD = 12.8) for the group that had
      not used opioids before TKA and 46.9 points (SD = 15.7) for those who had used
      opioids (p = 0.12). The mean preoperative Pain Catastrophizing Scale score was
      greater among opioid users (15.5 compared with 10.7 points among non-users, p =
      0.006). Adjusted analyses showed that the opioid group had a mean 6-month
      reduction in the WOMAC pain score of 27.0 points (95% confidence interval [CI] =
      22.7 to 31.3) compared with 33.6 points (95% CI = 31.4 to 35.9) in the non-opioid
      group (p = 0.008). CONCLUSIONS: Patients who used opioids prior to TKA obtained
      less pain relief from the operation. Clinicians should consider limiting pre-TKA
      opioid prescriptions to optimize the benefits of TKA. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 28509821
TI  - Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO):
      Platelet-Rich Plasma and Mesenchymal Stem Cells.
AB  - BACKGROUND: A comprehensive approach to the evaluation of biologic therapies for
      musculoskeletal conditions is required to guide appropriate future use. Clinical
      studies evaluating platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs)
      are limited by inadequate reporting of scientific details critical to outcome. We
      developed minimum reporting requirements for clinical studies evaluating PRP and
      MSCs using Delphi consensus methods. METHODS: The need for consensus on the
      minimum reporting requirements for studies evaluating biologics was identified at
      the American Academy of Orthopaedic Surgeons/Orthopaedic Research Society
      (AAOS/ORS) Biologic Treatments for Orthopaedic Injuries Symposium in 2015 and the
      American Orthopaedic Society for Sports Medicine (AOSSM) Biologic Treatments for
      Sports Injuries II Think Tank in 2015. A working group facilitated the
      development of 2 expert consensus statements for PRP and MSCs using Delphi
      techniques. Exhaustive lists of items that could be reported on by clinical
      studies evaluating PRP or MSCs were generated by searching the published
      literature and protocols. PRP and MSC expert groups, each made up of 24 invited
      speakers at the AAOS and AOSSM symposia, were surveyed on 3 occasions to
      establish consensus on the inclusion of each item within minimum reporting
      guidelines. In addition to rating their agreement, the experts were encouraged to
      propose further items or modifications. Predefined criteria were used to refine
      item lists after each survey. Final lists were compiled into checklist statements
      by the working group. RESULTS: For PRP, the working group identified 93
      experimental information items from the literature. Twenty-three experts (96%)
      completed 3 rounds of surveys. After 3 rounds, 58 items generated consensus with
      >75% agreement and <5% disagreement. These items were compiled into a 23
      statement checklist. For MSCs, 103 items were identified from the published
      literature. Twenty-three experts (96%) completed 3 rounds of surveys. After 3
      rounds, the 61 items for which consensus was reached were compiled into a 25
      statement checklist. CONCLUSIONS: This study has established expert consensus on
      the minimum reporting requirements for clinical studies evaluating PRP and MSCs.
      CLINICAL RELEVANCE: These checklists provide specifications for the minimum
      information that should be reported by clinical studies evaluating PRP or MSCs.

PMID- 28509822
TI  - Fracture Prevention in the Orthopaedic Environment: Outcomes of a Coordinator
      Based Fracture Liaison Service.
AB  - BACKGROUND: Fracture liaison services focus on secondary fracture prevention by
      identifying patients at risk for future fracture and initiating appropriate
      evaluation, risk assessment, education, and therapeutic intervention. This study
      describes key clinical outcomes including bone mineral densitometry, physician
      assessment, and pharmacotherapy initiation in pharmacotherapy-naive patients
      undergoing treatment for fragility fracture in a Canadian fracture liaison
      service. METHODS: We determined rates of post-fracture investigation and
      treatment for inpatients and outpatients with a fragility fracture seen in a
      coordinator-based fracture liaison service at an urban university trauma
      hospital. The program identified distal radial, proximal femoral, proximal
      humeral, and vertebral fragility fractures in female patients >=40 years of age
      and male patients >=50 years of age and provided education, bone mineral
      densitometry, inpatient consultation or outpatient specialist or primary care
      physician referral for bone health management, and documented patient follow-up.
      RESULTS: The 2,191 patients with a fragility fracture were not taking anti
      osteoporosis pharmacotherapy at the time of identification (862 inpatients and
      1,329 outpatients). Eighty-four percent of inpatients and 85% of outpatients
      completed a bone mineral densitometry as recommended. Fifty-two percent of
      patients with proximal femoral fracture, 29% of patients with vertebral fracture,
      26% of patients with proximal humeral fracture, and 20% of patients with distal
      radial fracture had osteoporosis confirmed on the basis of a bone mineral
      densitometry T-score of <=-2.5 at the femoral neck or L1 to L4. Eighty-five
      percent of inpatients and 79% of outpatients referred for bone health management
      were assessed by a specialist or primary care physician. Of the patients who
      attended their appointments, 73% of inpatients and 52% of outpatients received a
      prescription for anti-osteoporosis medication. CONCLUSIONS: A high rate of
      education, evaluation, and pharmacological treatment, if indicated, can be
      achieved through a coordinator-facilitated fracture liaison service program.
      CLINICAL RELEVANCE: Fracture prevention programs are currently engaged in
      establishing and modifying fracture liaison services in a quest for practical and
      effective models. The program described in this article exemplifies a coordinator
      based model that produced good outcomes.

PMID- 28509824
TI  - Implant Survival After Minimally Invasive Anterior or Anterolateral Vs.
      Conventional Posterior or Direct Lateral Approach: An Analysis of 21,860 Total
      Hip Arthroplasties from the Norwegian Arthroplasty Register (2008 to 2013).
AB  - BACKGROUND: Since 2008, there has been an increase in the use of minimally
      invasive surgery (MIS) through an anterior or anterolateral approach for total
      hip arthroplasty (THA) in Norway. We compared the MIS approaches with the
      conventional posterior and direct lateral approaches in terms of revision rates
      and risk of revision. METHODS: On the basis of data in the Norwegian Arthroplasty
      Register, 21,860 THAs with an uncemented stem, performed between 2008 and 2013,
      were identified and included in the cohort. Of these THAs, 2,017 were done
      through an MIS anterior approach; 2,087, through an MIS anterolateral approach;
      5,961, through a posterior approach; and 11,795, through a direct lateral
      approach. Follow-up ended on December 31, 2015. Two and 5-year survival rates
      were calculated using Kaplan-Meier survival analysis. Relative risk (RR) was
      calculated using Cox regression analysis, with adjustment for age, sex, primary
      diagnosis, American Society of Anesthesiologists (ASA) grade, femoral head size,
      cup fixation, type of articulation, and duration of surgery and using 6 revision
      end points based on cause: any cause, infection, dislocation, femoral fracture,
      aseptic loosening, and other/unknown cause. The median duration of follow-up was
      4.3 years. RESULTS: There were no significant differences among the surgical
      approaches with regard to the 2 and 5-year survival rates or RR of revision due
      to any cause. The RR of revision due to infection was 0.53 (95% confidence
      interval [CI] = 0.36 to 0.80, p = 0.002) for the MIS anterior and anterolateral
      approaches and 0.57 (95% CI = 0.40 to 0.80, p = 0.001) for the posterior approach
      compared with the direct lateral approach. The RR of revision due to dislocation
      was 2.1 (95% CI = 1.5 to 3.1, p < 0.001) for the posterior approach compared with
      the direct lateral approach but no significant difference in risk was found when
      the MIS anterior and anterolateral approaches were compared with the direct
      lateral approach (RR = 0.71, 95% CI = 0.40 to 1.3, p = 0.25). CONCLUSIONS: The
      revision rates and risk of revision associated with the MIS anterior and
      anterolateral approaches were not increased compared with those of the
      conventional posterior and direct lateral approaches. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 28509823
TI  - Progression of Fatty Muscle Degeneration in Atraumatic Rotator Cuff Tears.
AB  - BACKGROUND: The purpose of this prospective study was to examine the progression
      of fatty muscle degeneration over time in asymptomatic shoulders with
      degenerative rotator cuff tears. METHODS: Subjects with an asymptomatic rotator
      cuff tear in 1 shoulder and pain due to rotator cuff disease in the contralateral
      shoulder were enrolled in a prospective cohort. Subjects were followed annually
      with shoulder ultrasonography, which evaluated tear size, location, and fatty
      muscle degeneration. Tears that were either full-thickness at enrollment or
      progressed to a full-thickness defect during follow-up were examined. A minimum
      follow-up of 2 years was necessary for eligibility. RESULTS: One hundred and
      fifty-six shoulders with full-thickness rotator cuff tears were potentially
      eligible. Seventy shoulders had measurable fatty muscle degeneration of at least
      1 rotator cuff muscle at some time point. Patients with fatty muscle degeneration
      in the shoulder were older than those without degeneration (mean, 65.8 years [95%
      confidence interval (CI), 64.0 to 67.6 years] compared with 61.0 years [95% CI,
      59.1 to 62.9 years]; p < 0.05), and the median size of the tears at baseline was
      larger in shoulders with degeneration than in shoulders that did not develop
      degeneration (13 and 10 mm wide, respectively, and 13 and 10 mm long; p < 0.05).
      Tears with fatty muscle degeneration were more likely to have enlarged during
      follow-up than were tears that never developed muscle degeneration (79% compared
      with 58%; odds ratio, 2.64 [95% CI, 1.29 to 5.39]; p < 0.05). Progression of
      fatty muscle degeneration occurred more frequently in shoulders with tears that
      had enlarged (43%; 45 of 105) than in shoulders with tears that had not enlarged
      (20%; 10 of 51; p < 0.05). Additionally, tears with enlargement and progression
      of muscle degeneration were more likely to extend into the anterior supraspinatus
      than were those without progression (53% and 17%, respectively; p < 0.05);
      however, this relationship was lost when controlling for tear size (p = 0.56).
      The median time from tear enlargement to progression of fatty muscle degeneration
      was 1.0 year (range, -2.0 to 6.9 years) for the supraspinatus and 1.1 years
      (range, -1.8 to 8.5 years) for the infraspinatus muscle (p = 0.98). CONCLUSIONS:
      Progression of fatty muscle degeneration is more common in tears that are larger
      at baseline, enlarge over time, and undergo a larger magnitude of enlargement.
      Our study findings also suggest that an often rapid progression of muscle
      degeneration occurs in relation to a clinically relevant increase in tear size in
      some degenerative cuff tears. LEVEL OF EVIDENCE: Prognostic Level II. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 28509825
TI  - Vascularized Pedicle Bone-Grafting from the Cuboid for Talar Osteonecrosis:
      Results of a Novel Salvage Procedure.
AB  - BACKGROUND: Osteonecrosis of the talar body represents a complex clinical
      challenge with treatment options currently limited to core decompression,
      vascularized and nonvascularized bone-grafting, total talar replacement, and
      hindfoot arthrodesis. Vascularized pedicle bone-grafting from the cuboid to the
      talus is a potential alternative to contemporary operative options for
      replacement of necrotic talar tissue with viable bone. We aimed to analyze
      functional and radiographic outcomes of vascularized pedicle bone-grafting from
      the cuboid for the treatment of talar osteonecrosis in a consecutive series of
      patients spanning a 12-year period. METHODS: Patients with osteonecrosis of the
      talar body and dome who underwent vascularized pedicle bone-grafting from the
      cuboid to the talus at our institution between 2003 and 2014 were retrospectively
      identified. All patients had preoperative radiographs and magnetic resonance
      imaging (MRI) scans and were monitored postoperatively with serial radiographs
      and MRI. For generic health-related quality-of-life (HRQoL) assessment, patients
      were given the preoperative Medical Outcomes Study Short Form-12 (SF-12) and
      postoperative 36-Item Short Form (SF-36) from which Physical Component Summary
      (PCS) and Mental Component Summary (MCS) scores were derived and compared before
      and after surgery. RESULTS: Thirteen patients were identified and sequentially
      followed for 2 to 12 years (mean, 6 years). Two patients had failure of treatment
      and subsequently underwent total ankle replacement, 1 patient had arthroscopic
      debridement for soft-tissue impingement, and no other patient required secondary
      surgery. The average PCS score (and standard deviation) significantly improved by
      23.3 +/- 18.9 points with surgery (p = 0.006), and the average MCS score
      significantly increased by 39.4 +/- 10.1 points (p < 0.001). CONCLUSIONS: HRQoL
      outcomes suggest that vascularized pedicle bone-grafting from the cuboid combined
      with bracing for 1 year may be a viable treatment option for osteonecrosis of the
      talus that provides good pain relief and improved physical function without
      necessitating a secondary procedure for the majority of patients. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 28509826
TI  - Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an
      Animal Model.
AB  - BACKGROUND: Rotator cuff tears are a common source of pain and disability, and
      poor healing after repair leads to high retear rates. Bone loss in the humeral
      head before and after repair has been associated with poor healing. The purpose
      of the current study was to mitigate bone loss near the repaired cuff and improve
      healing outcomes. METHODS: Sclerostin antibody (Scl-Ab) treatment, previously
      shown to increase bone formation and strength in the setting of osteoporosis, was
      used in the current study to address bone loss and enhance rotator cuff healing
      in an animal model. Scl-Ab was administered subcutaneously at the time of rotator
      cuff repair and every 2 weeks until the animals were sacrificed. The effect of
      Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone
      morphometric analysis, biomechanical evaluation, histological analysis, and gene
      expression outcomes. RESULTS: Injury and repair led to a reduction in bone
      mineral density after 2 and 4 weeks of healing in the control and Scl-Ab
      treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment
      had 30% greater bone mineral density than the controls. A decrease in
      biomechanical properties was observed in both groups after 4 weeks of healing
      compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl
      Ab-treated animals had improved strength (38%) and stiffness (43%) compared with
      control animals. Histological assessment showed that Scl-Ab promoted better
      integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant
      effects on gene expression in bone, indicative of enhanced bone formation, and no
      effect on the expression of genes in tendon. CONCLUSIONS: This study provides
      evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator
      cuff by increasing attachment-site bone mineral density, leading to improved
      biomechanical properties. CLINICAL RELEVANCE: Scl-Ab treatment may improve
      outcomes after rotator cuff repair.

PMID- 28509829
TI  - In Total Knee Arthroplasty, Patient-Matched Positioning Guides and Conventional
      Instruments Did Not Differ in Terms of Clinical Outcomes or Complications at Two
      Years.

PMID- 28509827
TI  - Leptin Elevation as a Risk Factor for Slipped Capital Femoral Epiphysis
      Independent of Obesity Status.
AB  - BACKGROUND: Slipped capital femoral epiphysis (SCFE) is strongly associated with
      childhood obesity, yet the prevalence of obesity is orders of magnitude greater
      than the prevalence of SCFE. Therefore, it is hypothesized that obesity is not,
      by itself, a sufficient condition for SCFE, but rather one component of a
      multifactorial process requiring preexisting physeal pathology. Leptin elevation
      is seen to varying degrees in patients with obesity, and as leptin has been shown
      to cause physeal pathology similar to the changes seen in SCFE, we propose that
      leptin may be a factor distinguishing between patients with SCFE and equally
      obese children without hip abnormalities. METHODS: Serum leptin levels were
      obtained from 40 patients with SCFE and 30 control patients with approximate body
      mass index (BMI) matching. BMI percentiles were calculated according to Centers
      for Disease Control and Prevention population data by patient age and sex.
      Patients were compared by demographic characteristics, leptin levels, odds of
      leptin elevation, and odds of SCFE. RESULTS: The odds of developing SCFE was
      increased by an odds ratio of 4.9 (95% confidence interval [CI], 1.31 to 18.48; p
      < 0.02) in patients with elevated leptin levels, regardless of obesity status,
      sex, and race. When grouping patients by their obesity status, non-obese patients
      with SCFE showed elevated median leptin levels at 5.8 ng/mL compared with non
      obese controls at 1.7 ng/mL (p = 0.006). Similarly, obese patients with SCFE
      showed elevated median leptin levels at 17.9 ng/mL compared with equally obese
      controls at 10.5 ng/mL (p = 0.039). Serum leptin levels increased in association
      with obesity (p < 0.001), with an increase in leptin of 0.17 ng/mL (95% CI, 0.07
      to 0.27 ng/mL) per BMI percentile point. CONCLUSIONS: To our knowledge, this
      study is the first to clinically demonstrate an association between elevated
      serum leptin levels and SCFE, regardless of BMI. This adds to existing literature
      suggesting that SCFE is a multifactorial process and that leptin levels may have
      profound physiological effects on the development of various disease states.
      Despite a strong association with adiposity, leptin levels vary between patients
      of equal BMI and may be a vital resource in prognostication of future obesity
      related comorbidities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 28509828
TI  - Modular Fluted Tapered Stems in Aseptic Revision Total Hip Arthroplasty.
AB  - BACKGROUND: Modular fluted tapered stems have become the most commonly employed
      category of femoral component in revision hip arthroplasty in North America as a
      result of favorable early results and simplicity of use. Despite wide adoption,
      the majority of published data are limited to relatively small series with modest
      follow-up. The goal of the current study was to determine the success rate and
      factors associated with success, failure, and complications of the use of modular
      fluted tapered stems in aseptic revision total hip arthroplasties (THAs) in a
      large patient cohort. METHODS: We identified 519 aseptic femoral revisions during
      which a modular fluted tapered stem was utilized. Clinical outcomes, Kaplan-Meier
      survivorship, radiographic outcomes, and complications were assessed. The mean
      age at revision arthroplasty was 70 years, the mean body mass index (BMI) was 29
      kg/m, and the mean duration of follow-up was 4.5 years (range, 2 to 14 years).
      RESULTS: The mean Harris hip score (HHS) improved significantly from 51 points
      preoperatively to 76 points at 2 years (p < 0.001). This improvement was
      maintained at the last follow-up evaluation (mean HHS = 75 points). At the time
      of the most recent follow-up, 16 femoral revisions had been performed: 6 because
      of aseptic loosening, 4 because of infection, 3 because of instability, 2 because
      of periprosthetic fracture, and 1 because of stem fracture. The 10-year
      survivorship was 96% with revision for any reason as the end point and 90% with
      any reoperation as the end point. Of the patients who were alive and had not
      undergone revision at the time of final follow-up, 12 had stem subsidence but all
      but 1 of these stems had stabilized after subsiding. Postoperative complications
      were noted in 12% of the cases. Repeat revision due to femoral component
      loosening was not correlated with the preoperative bone-loss category or patient
      demographic factors. CONCLUSIONS: In this large series, femoral revision with a
      modular fluted tapered stem provided a high rate of osseointegration and
      sustained improvement in clinical scores at the time of the last follow-up. There
      was also a high rate of successful implant fixation across all categories of
      preoperative bone loss and an acceptable rate of complications. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 28509830
TI  - Using Small Intestine Submucosa to Augment Repair of Moderate to Large Rotator
      Cuff Tears Did Not Reduce Repair Failures.

PMID- 28509831
TI  - Fibular Nailing Did Not Differ from Standard Open Reduction and Internal Fixation
      for Unstable Ankle Fractures in Elderly Patients.

PMID- 28509832
TI  - What's New in Sports Medicine.

PMID- 28509833
TI  - Minimum Five-Year Outcomes with Porous Tantalum Acetabular Cup and Augment
      Construct in Complex Revision Total Hip Arthroplasty.
AB  - BACKGROUND: The use of a trabecular metal revision shell with metal augmentation
      to fill segmental or irregular defects during complex revision hip arthroplasty
      has been shown to provide good short-term results in prior published series.
      Longer-term results of the several cup-augment constructs used clinically are not
      known. The objective of this study was to report, with minimum 5-year
      radiographic and clinical follow-up, the outcome of these various constructs in
      revision total hip arthroplasty. METHODS: Eighty-four patients (85 hips)
      underwent revision total hip arthroplasty with use of porous tantalum augments
      between 2000 and 2007 at a single institution and were retrospectively reviewed.
      Fifty-seven of the patients (58 hips) had clinical and radiographic follow-up at
      a minimum of 5 years. At the time of revision, the majority of the hips had
      acetabular defects classified as Paprosky Type 3A (28 of 58, 48%) or Type 3B (22
      of 58, 38%). Eleven (19%) of the hips also had preoperative pelvic discontinuity.
      All hips were assessed clinically at a minimum of 5 years with use of the Mayo
      hip score. Postoperative radiographs were reviewed for implant stability, the
      presence and location of radiolucent lines and healing of the discontinuity if
      present. RESULTS: In 2 (3%) of the 58 hips, the constructs failed because of
      aseptic loosening of the acetabular component and re-revision was indicated. Six
      (10%) of the 58 hips demonstrated a radiolucent line between the trabecular metal
      shell and bone in DeLee and Charnley zone 3. In 1 hip that underwent re-revision
      and in 5 of the 6 hips with a zone-3 radiolucency, a pelvic discontinuity was
      present at the time of the index revision. The mean preoperative Mayo hip score
      was 35.7, which improved to 61.9 at 3 months and was 61.7 at the minimum 5-year
      follow-up. CONCLUSIONS: With failure defined as aseptic loosening requiring
      repeat revision surgery, this cohort demonstrated 97% survivorship and maintained
      satisfactory hip function at the minimum 5 years after the index revision
      surgery. Six of the 11 hips with preoperative pelvic discontinuity either failed
      or developed a radiolucency in zone 3 and are considered at risk for future
      revision. Pelvic discontinuity should prompt consideration of the addition of
      adjunctive fixation or the use of alternative techniques. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 28509834
TI  - Decisions and Incisions: A Value-Driven Practice Framework for Academic Surgeons.

PMID- 28509835
TI  - Changes by the Accreditation Council for Graduate Medical Education: Success or
      Failure?: An AOA Critical Issues Symposium.
AB  - The Accreditation Council for Graduate Medical Education has introduced far
      reaching changes to the educational requirements for postgraduate trainees over
      the past 15 years. These steps were taken to improve the quality of education and
      to enhance patient safety. This symposium will explore the design and
      implementation of these changes and determine if they are succeeding.

PMID- 28509836
TI  - Make No Bones About It-Rotator Cuff Repair Healing Is Not Just About the Tendon:
      Commentary on an article by Shivam A. Shah, PhD, et al.: "Sclerostin Antibody
      Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model".

PMID- 28509837
TI  - The End of the Road for Idiopathic Slipped Capital Femoral Epiphysis?: Commentary
      on an article by Schuyler J. Halverson, MD, MS, et al.: "Leptin Elevation as a
      Risk Factor for Slipped Capital Femoral Epiphysis Independent of Obesity Status".

PMID- 28509838
TI  - Long-Term Effect of a Stigma-Reduction Educational Intervention for Physician
      Assistants.
AB  - PURPOSE: Stigma towards people with substance use disorders is a common
      phenomenon with far reaching effects. This study evaluated the long-term effect
      of using an educational intervention on the attitudes of physician assistant
      students. METHODS: Physician assistant students received a one-week educational
      intervention focused on substance abuse. Changes in student attitudes were
      measured one year later using the Attitude to Mental Health Questionnaire (AMIQ).
      RESULTS: Significant and sustained improvement was noted in attitudes in the AMIQ
      score for the opiate use disorder vignette; no significant change was noted in
      the alcohol use disorder vignette. CONCLUSIONS: The persistence of improved
      attitudes (although they remained negative) in study participants towards people
      with opiate use disorders is a cautiously encouraging finding. Educational
      interventions can have a sustained effect on stigma reduction, but much more work
      on the etiology of these implicit and explicit beliefs is needed to inform robust
      future interventions.

PMID- 28509839
TI  - Autonomy, Authenticity, and Deferred Decision Making: The Practical Application
      of Abstract Concepts for Physician Assistants.

PMID- 28509840
TI  - Negotiating on Behalf of Your Program.

PMID- 28509841
TI  - Simultaneous Wireless Power Transfer and Secure Multicasting in Cooperative
      Decode-and-Forward Relay Networks.
AB  - In this paper, we investigate simultaneous wireless power transfer and secure
      multicasting via cooperative decode-and-forward (DF) relays in the presence of
      multiple energy receivers and eavesdroppers. Two scenarios are considered under a
      total power budget: maximizing the minimum harvested energy among the energy
      receivers under a multicast secrecy rate constraint; and maximizing the multicast
      secrecy rate under a minimum harvested energy constraint. For both scenarios, we
      solve the transmit power allocation and relay beamformer design problems by using
      semidefinite relaxation and bisection technique. We present numerical results to
      analyze the energy harvesting and secure multicasting performances in cooperative
      DF relay networks.

PMID- 28509843
TI  - Modeling the Footprint and Equivalent Radiance Transfer Path Length for Tower
      Based Hemispherical Observations of Chlorophyll Fluorescence.
AB  - The measurement of solar-induced chlorophyll fluorescence (SIF) is a new tool for
      estimating gross primary production (GPP). Continuous tower-based spectral
      observations together with flux measurements are an efficient way of linking the
      SIF to the GPP. Compared to conical observations, hemispherical observations made
      with cosine-corrected foreoptic have a much larger field of view and can better
      match the footprint of the tower-based flux measurements. However, estimating the
      equivalent radiation transfer path length (ERTPL) for hemispherical observations
      is more complex than for conical observations and this is a key problem that
      needs to be addressed before accurate retrieval of SIF can be made. In this
      paper, we first modeled the footprint of hemispherical spectral measurements and
      found that, under convective conditions with light winds, 90% of the total
      radiation came from an FOV of width 72 degrees , which in turn covered 75.68% of
      the source area of the flux measurements. In contrast, conical spectral
      observations covered only 1.93% of the flux footprint. Secondly, using
      theoretical considerations, we modeled the ERTPL of the hemispherical spectral
      observations made with cosine-corrected foreoptic and found that the ERTPL was
      approximately equal to twice the sensor height above the canopy. Finally, the
      modeled ERTPL was evaluated using a simulated dataset. The ERTPL calculated using
      the simulated data was about 1.89 times the sensor's height above the target
      surface, which was quite close to the results for the modeled ERTPL. Furthermore,
      the SIF retrieved from atmospherically corrected spectra using the modeled ERTPL
      fitted well with the reference values, giving a relative root mean square error
      of 18.22%. These results show that the modeled ERTPL was reasonable and that this
      method is applicable to tower-based hemispherical observations of SIF.

PMID- 28509842
TI  - Molecular Epidemiology of Methicillin-Resistant and Methicillin-Susceptible
      Staphylococcus aureus in the Ovine Dairy Chain and in Farm-Related Humans.
AB  - Staphylococcus aureus is a major cause of clinical infections in humans and its
      enterotoxins cause foodborne disease. In the present study, we tested a total of
      51 isolates of S. aureus from small-ruminant dairy farms with artisan dairy
      facilities, all located in Latium, Italy. The farms have a known history of a
      high prevalence of methicillin-resistant S. aureus (MRSA). Most of the MRSA
      isolates (27 of 51) belonged to spa-type t127 (43.1%), followed by t2678 (3.9%),
      t044 (2%), t1166 (2%), and t1773 (2%). PFGE performed on mecA positive strains
      identified one cluster (>= 80% of similarity), comprising 22 MRSA. Nine of twenty
      two MRSA isolates were assigned human host origin, and 13 isolates did not belong
      to a specific host. During the characterization study, one strain isolated from
      bulk tank milk samples harbored the pvl gene; the strain was not enterotoxigenic
      with a non-specific host according to the biotyping scheme, highlighting the
      possible emerging risk of transmission of bacterial virulence factors by foods,
      the environment, and foodhandlers. These findings stress the importance of
      hygienic measures at all processing steps of the food production chain and
      underline that monitoring for the presence of MRSA throughout the food chain is
      essential for public health.

PMID- 28509844
TI  - Influence of Nano-Hydroxyapatite on the Metal Bioavailability, Plant Metal
      Accumulation and Root Exudates of Ryegrass for Phytoremediation in Lead-Polluted
      Soil.
AB  - Lead is recognized as one of the most widespread toxic metal contaminants and
      pervasive environmental health concerns in the environment. In this paper, the
      effects of nano-hydroxyapatite (NHAP) on remediation in artificially Pb
      contaminated soils and ryegrass were studied in a pot experiment. The addition of
      NHAP decreased the water- and acid-soluble, exchangeable, and reducible fractions
      of Pb, extracted using the Community Bureau of Reference (BCR) method, whilst
      greatly increasing the residual fraction of Pb. Oxidizable Pb was increased
      slightly. No significant increase in soil pH was caused by the application of
      NHAP. Compared to conditions without NHAP, the addition of NHAP decreased the Pb
      content in ryegrass shoots and roots by 13.19-20.3% and 2.86-21.1%, respectively.
      Therefore, the application of NHAP reduced the mobility and bioavailability of Pb
      in the soil. In addition, the application of NHAP improved the fresh weight of
      shoots and roots, and promoted the growth of ryegrass. NHAP played a positive
      role in stimulating ryegrass to secrete tartaric acid.

PMID- 28509847
TI  - A Robust Method to Detect BeiDou Navigation Satellite System Orbit
      Maneuvering/Anomalies and Its Applications to Precise Orbit Determination.
AB  - The failure to detect anomalies and maneuvering of the orbits of navigation
      satellite sensors will deteriorate the performance of positioning and orbit
      determination. Motivated by the influence of the frequent maneuvering of BDS GEO
      and IGSO satellites, this paper analyzes the limitations of existing methods,
      where BDS orbit maneuvering and anomalies can be detected, and develops a method
      to solve this problem based on the RMS model of orbit mutual differences proposed
      in this paper. The performance of this method was assessed by comparison with the
      health flag of broadcast ephemeris, precise orbit products of GFZ, the O-C values
      of a GNSS station and a conventional method. The results show that the
      performance of the method developed in this paper is better than that of the
      conventional method when the periodicity and trend items are obvious. Meanwhile,
      three additional verification results show that the method developed in this
      paper can find error information in the merged broadcast ephemeris provided by
      iGMAS. Furthermore, from the testing results, it can be seen that the detection
      of anomaly and maneuvering items do not affect each other based on the robust
      thresholds constructed in this paper. In addition, the precise orbit of the
      maneuvering satellites can be determined under the circumstances that the
      maneuver information detected in this paper is used, and the root mean square
      (RMS) of orbit overlap comparison for GEO-03/IGSO-03 in Radial, Along, Cross, 1D
      RMS are 0.7614/0.4460 m, 1.8901/0.3687 m, 0.3392/0.2069 m, 2.0657/0.6145 m,
      respectively.

PMID- 28509845
TI  - Metabolic Portraits of Breast Cancer by HR MAS MR Spectroscopy of Intact Tissue
      Samples.
AB  - Despite progress in early detection and therapeutic strategies, breast cancer
      remains the second leading cause of cancer-related death among women globally.
      Due to the heterogeneity and complexity of tumor biology, breast cancer patients
      with similar diagnosis might have different prognosis and response to treatment.
      Thus, deeper understanding of individual tumor properties is necessary. Cancer
      cells must be able to convert nutrients to biomass while maintaining energy
      production, which requires reprogramming of central metabolic processes in the
      cells. This phenomenon is increasingly recognized as a potential target for
      treatment, but also as a source for biomarkers that can be used for prognosis,
      risk stratification and therapy monitoring. Magnetic resonance (MR) metabolomics
      is a widely used approach in translational research, aiming to identify
      clinically relevant metabolic biomarkers or generate novel understanding of the
      molecular biology in tumors. Ex vivo proton high-resolution magic angle spinning
      (HR MAS) MR spectroscopy is widely used to study central metabolic processes in a
      non-destructive manner. Here we review the current status for HR MAS MR
      spectroscopy findings in breast cancer in relation to glucose, amino acid and
      choline metabolism.

PMID- 28509846
TI  - A New Ergosterol Analog, a New Bis-Anthraquinone and Anti-Obesity Activity of
      Anthraquinones from the Marine Sponge-Associated Fungus Talaromyces stipitatus
      KUFA 0207.
AB  - A new ergosterol analog, talarosterone (1) and a new bis-anthraquinone derivative
      (3) were isolated, together with ten known compounds including palmitic acid,
      ergosta-4,6,8(14),22-tetraen-3-one, ergosterol-5,8-endoperoxide, cyathisterone
      (2), emodin (4a), questinol (4b), citreorosein (4c), fallacinol (4d), rheoemodin
      (4e) and secalonic acid A (5), from the ethyl acetate extract of the culture of
      the marine sponge-associated fungus Talaromyces stipitatus KUFA 0207. The
      structures of the new compounds were established based on extensive 1D and 2D
      spectral analysis, and in the case of talarosterone (1), the absolute
      configurations of its stereogenic carbons were determined by X-ray
      crystallographic analysis. The structure and stereochemistry of cyathisterone (2)
      was also confirmed by X-ray analysis. The anthraquinones 4a-e and secalonic acid
      A (5) were tested for their anti-obesity activity using the zebrafish Nile red
      assay. Only citreorosein (4c) and questinol (4b) exhibited significant anti
      obesity activity, while emodin (4a) and secalonic acid A (5) caused toxicity
      (death) for all exposed zebrafish larvae after 24 h.

PMID- 28509848
TI  - Biosensor Based on Tyrosinase Immobilized on Graphene-Decorated Gold
      Nanoparticle/Chitosan for Phenolic Detection in Aqueous.
AB  - In this research work, electrochemical biosensor was fabricated based on
      immobilization of tyrosinase onto graphene-decorated gold nanoparticle/chitosan
      (Gr-Au-Chit/Tyr) nanocomposite-modified screen-printed carbon electrode (SPCE)
      for the detection of phenolic compounds. The nanocomposite film was constructed
      via solution casting method. The electrocatalytic activity of the proposed
      biosensor for phenol detection was studied using differential pulse voltammetry
      (DPV) and cyclic voltammetry (CV). Experimental parameters such as pH buffer,
      enzyme concentration, ratio of Gr-Au-Chit, accumulation time and potential were
      optimized. The biosensor shows linearity towards phenol in the concentration
      range from 0.05 to 15 MUM with sensitivity of 0.624 MUA/MUM and the limit of
      detection (LOD) of 0.016 MUM (S/N = 3). The proposed sensor also depicts good
      reproducibility, selectivity and stability for at least one month. The biosensor
      was compared with high-performance liquid chromatography (HPLC) method for the
      detection of phenol spiked in real water samples and the result is in good
      agreement and comparable.

PMID- 28509849
TI  - Low Duty-Cycling MAC Protocol for Low Data-Rate Medical Wireless Body Area
      Networks.
AB  - Wireless body area networks (WBANs) are severely energy constrained, and how to
      improve the energy efficiency so as to prolong the network lifetime as long as
      possible is one of the most important goals of WBAN research. Low data-rate WBANs
      are promising to cut down the energy consumption and extend the network lifetime.
      Considering the characteristics and demands of low data-rate WBANs, a low duty
      cycling medium access control (MAC) protocol is specially designed for this kind
      of WBAN in this paper. Longer superframes are exploited to cut down the energy
      consumed on the transmissions and receptions of redundant beacon frames.
      Insertion time slots are embedded into the inactive part of a superframe to
      deliver the frames and satisfy the quality of service (QoS) requirements. The
      number of the data subsections in an insertion time slot can be adaptively
      adjusted so as to accommodate low data-rate WBANs with different traffic.
      Simulation results show that the proposed MAC protocol performs well under the
      condition of low data-rate monitoring traffic.

PMID- 28509850
TI  - Accessing Mefenamic Acid Form II through High-Pressure Recrystallisation.
AB  - High-pressure crystallisation has been successfully used as an alternative
      technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic
      acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was
      grown at 0.3 GPa from an ethanolic solution by using a diamond anvil cell. A
      comparison of the crystal structures shows that the efficient packing of
      molecules in Form II was enabled by the structural flexibility of MA molecules.
      Compression studies performed on a single crystal of Form I resulted in a 14%
      decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up
      to this pressure. A reconstructive phase transition is required to induce
      conformational changes in the structure, which was confirmed by the results of
      crystallisation at high pressure.

PMID- 28509851
TI  - Development of a Flow Injection Based High Frequency Dual Channel Quartz Crystal
      Microbalance.
AB  - When the quartz crystal microbalance (QCM) is used in liquid for adsorption or
      desorption monitoring based bio- or chemical sensing applications, the frequency
      shift is not only determined by the surface mass change, but also by the change
      of liquid characteristics, such as density and viscosity, which are greatly
      affected by the liquid environmental temperature. A monolithic dual-channel QCM
      is designed and fabricated by arranging two QCM resonators on one single chip for
      cancelling the fluctuation induced by environmental factors. In actual
      applications, one QCM works as a specific sensor by modifying with functional
      membranes and the other acts as a reference, only measuring the liquid property.
      The dual-channel QCM is designed with an inverted-mesa structure, aiming to
      realize a high frequency miniaturized chip and suppress the frequency
      interference between the neighbored QCM resonators. The key problem of dual
      channel QCMs is the interference between two channels, which is influenced by the
      distance of adjacent resonators. The diameter of the reference electrode has been
      designed into several values in order to find the optimal parameter. Experimental
      results demonstrated that the two QCMs could vibrate individually and the output
      frequency stability and drift can be greatly improved with the aid of the
      reference QCM.

PMID- 28509853
TI  - Predictors of Caregiver Burden among Mothers of Children with Chronic Conditions.
AB  - OBJECTIVE: The complex medical regimens of children and adolescents with chronic
      conditions can have a significant impact on families and households. Caregivers
      may experience burden, which can lead to negative health consequences and poor
      quality of life. The objective of this study was to determine child-related
      predictors and risk factors for caregiver burden among parents of children with
      chronic conditions. METHODS: We distributed an institutional review board (IRB)
      approved, online cross-sectional survey to parents of children who attended the
      Victory Junction therapeutic camp. Parents provided information on child
      demographics, disease characteristics, and healthcare utilization. Parents also
      answered the adapted Zarit Burden Interview, which measured caregiver burden.
      Children completed scales about self-management and self-efficacy. Linear
      regression analyses determined how children's disease characteristics, health
      utilization, and self-management skills were associated with caregiver burden.
      RESULTS: We enrolled 150 mother-child dyads. The mean age of child participants
      was 12.23 years (+/-2.5), with an age range of 6 to 16 years. It was determined
      that children's number of medicines and injections (beta = 0.161, p = 0.047), a
      diagnosis of attention-deficit/hyperactivity disorder (ADHD) in addition to the
      primary medical condition (beta = 0.216, p = 0.008), frequent visits with a
      primary care provider (PCP) (beta = 0.209, p = 0.026) and emergency room (ER)
      visits (beta = 0.197, p = 0.038), and lower child self-efficacy (beta = -0.241, p
      = 0.041) were predictors of increased caregiver burden. CONCLUSIONS: We
      identified risk factors for caregiver burden among mothers. Future studies should
      explore additional child-related characteristics as they relate to caregiver
      burden, and should determine if interventions for mothers of children with
      chronic conditions can lead to positive outcomes.

PMID- 28509852
TI  - Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.
AB  - The management of patients with chronic respiratory diseases affected by
      difficult to treat infections has become a challenge in clinical practice.
      Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require
      extensive treatment strategies to deal with multidrug resistant pathogens that
      include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus,
      Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges
      prompted scientists to deliver antimicrobial agents through the pulmonary system
      by using inhaled, aerosolized or nebulized antibiotics. Subsequent research
      advances focused on the development of antibiotic agents able to achieve high
      tissue concentrations capable of reducing the bacterial load of difficult-to
      treat organisms in hosts with chronic respiratory conditions. In this review, we
      focus on the evidence regarding the use of antibiotic therapies administered
      through the respiratory system via inhalation, nebulization or aerosolization,
      specifically in patients with chronic respiratory diseases that include CF, non
      CF bronchiectasis and NTM. However, further research is required to address the
      potential benefits, mechanisms of action and applications of inhaled antibiotics
      for the management of difficult-to-treat infections in patients with chronic
      respiratory diseases.

PMID- 28509854
TI  - The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate
      Inflammatory Response through Inactivation of NF-kappaB and MAPKs in
      Lipopolysaccharide-Induced RAW264.7 Cells.
AB  - Mentha haplocalyx has been widely used for its flavoring and medicinal properties
      and as a traditional Chinese medicine with its anti-inflammation properties. The
      present study was designed to investigate the anti-inflammatory effects and
      potential molecular mechanisms of the phenolic fraction of M. haplocalyx (MHP)
      and its constituent linarin in lipopolysaccharide (LPS)-induced RAW264.7 cells.
      The high-performance liquid chromatography coupled with linear ion trap-orbitrap
      mass spectrometry (HPLC-LTQ-Orbitrap MS) was used to analyze the chemical
      composition of MHP. Using the enzyme-linked immunosorbent assay (ELISA) and
      quantitative realtime polymerase chain reaction (qRT-PCR), the expression of pro
      inflammatory meditators and cytokines was measured at the transcriptional and
      translational levels. Western blot analysis was used to further investigate
      changes in the nuclear factor kappa B (NF-kappaB), mitogen-activated protein
      kinase (MAPK), and Akt signaling pathways. Fourteen phenolic constituents were
      identified from MHP based on the data of the mass spectrometry (MS)/MS analysis.
      MHP and linarin decreased the production of NO, tumor necrosis factor-alpha (TNF
      alpha), interlenkin-1beta (IL-1beta), and IL-6. The messenger ribonucleic acid
      (mRNA) expression levels of inducible NO synthase (iNOS), TNF-alpha, IL-1beta,
      and IL-6 were also suppressed by MHP and linarin. Further investigation showed
      that MHP and linarin down-regulated LPS-induced phosphorylation content of NF
      kappaB p65, inhibitor kappa B alpha (IkappaBalpha), extracellular signal
      regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. However, MHP
      and linarin showed no inhibitory effect on the phosphorylated Akt. These results
      suggested that MHP and linarin exerted a potent inhibitory effect on pro
      inflammatory meditator and cytokines production via the inactivation of NF-kappaB
      and MAPKs, and they may serve as potential modulatory agents for the prevention
      and treatment of inflammatory diseases.

PMID- 28509855
TI  - The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel u-Opioid
      Agonist.
AB  - 5'-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1-12 were synthesized and a
      pharmacological screening of these derivatives was performed to identify a
      possible effect on the Central Nervous System (CNS) and to explore the associated
      mechanisms of action. The mice received a peritoneal injection (100 umol/kg) of
      each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital
      and the mean hypnosis times were recorded. The mean hypnosis time increased for
      the mice treated with PILAB 8, which was prevented when mice were administered
      CTOP, a u-opioid antagonist. Locomotor and motor activities were not affected by
      PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus
      maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent
      time in the open arms of the apparatus compared with the control group.
      Conversely, a decrease in the percentages of entries and time spent in the closed
      arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist,
      prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB
      8 exhibited antinociceptive activity in the hot plate test, and reduced
      reactivity to formalin in the neurogenic and the inflammatory phases. These data
      suggest that PILAB 8 can activate u-opioid receptors to provoke antinociceptive
      and anti-inflammatory effects in mice.

PMID- 28509856
TI  - First Report of a Fatal Case Associated with EV-D68 Infection in Hong Kong and
      Emergence of an Interclade Recombinant in China Revealed by Genome Analysis.
AB  - A fatal case associated with enterovirus D68 (EV-D68) infection affecting a 10
      year-old boy was reported in Hong Kong in 2014. To examine if a new strain has
      emerged in Hong Kong, we sequenced the partial genome of the EV-D68 strain
      identified from the fatal case and the complete VP1, and partial 5'UTR and 2C
      sequences of nine additional EV-D68 strains isolated from patients in Hong Kong.
      Sequence analysis indicated that a cluster of strains including the previously
      recognized A2 strains should belong to a separate clade, clade D, which is
      further divided into subclades D1 and D2. Among the 10 EV-D68 strains, 7
      (including the fatal case) belonged to the previously described, newly emerged
      subclade B3, 2 belonged to subclade B1, and 1 belonged to subclade D1. Three EV
      D68 strains, each from subclades B1, B3, and D1, were selected for complete
      genome sequencing and recombination analysis. While no evidence of recombination
      was noted among local strains, interclade recombination was identified in
      subclade D2 strains detected in mainland China in 2008 with VP2 acquired from
      clade A. This study supports the reclassification of subclade A2 into clade D1,
      and demonstrates interclade recombination between clades A and D2 in EV-D68
      strains from China.

PMID- 28509858
TI  - Modes of Cell Death Induced by Photodynamic Therapy Using Zinc Phthalocyanine in
      Lung Cancer Cells Grown as a Monolayer and Three-Dimensional Multicellular
      Spheroids.
AB  - Photodynamic therapy (PDT) involves interaction of a photosensitizer, light, and
      molecular oxygen which produces singlet oxygen and subsequent tumour eradication.
      The development of second generation photosensitizers, such as phthalocyanines,
      has improved this technology. Customary monolayer cell culture techniques are,
      unfortunately, too simple to replicate treatment effects in vivo. Multicellular
      tumour spheroids may provide a better alternative since they mimic aspects of the
      human tumour environment. This study aimed to profile 84 genes involved in
      apoptosis following treatment with PDT on lung cancer cells (A549) grown in a
      monolayer versus three-dimensional multicellular tumour spheroids (250 and 500
      MUm). Gene expression profiling was performed 24 h post irradiation (680 nm; 5
      J/cm2) with zinc sulfophthalocyanine (ZnPcSmix) to determine the genes involved
      in apoptotic cell death. In the monolayer cells, eight pro-apoptotic genes were
      upregulated, and two were downregulated. In the multicellular tumour spheroids
      (250 um) there was upregulation of only 1 gene while there was downregulation of
      56 genes. Apoptosis in the monolayer cultured cells was induced via both the
      intrinsic and extrinsic apoptotic pathways. However, in the multicellular tumour
      spheroids (250 and 500 um) the apoptotic pathway that was followed was not
      conclusive.

PMID- 28509860
TI  - A Combined Independent Source Separation and Quality Index Optimization Method
      for Fetal ECG Extraction from Abdominal Maternal Leads.
AB  - The non-invasive fetal electrocardiogram (fECG) technique has recently received
      considerable interest in monitoring fetal health. The aim of our paper is to
      propose a novel fECG algorithm based on the combination of the criteria of
      independent source separation and of a quality index optimization (ICAQIO-based).
      The algorithm was compared with two methods applying the two different criteria
      independently-the ICA-based and the QIO-based methods-which were previously
      developed by our group. All three methods were tested on the recently implemented
      Fetal ECG Synthetic Database (FECGSYNDB). Moreover, the performance of the
      algorithm was tested on real data from the PhysioNet fetal ECG Challenge 2013
      Database. The proposed combined method outperformed the other two algorithms on
      the FECGSYNDB (ICAQIO-based: 98.78%, QIO-based: 97.77%, ICA-based: 97.61%).
      Significant differences were obtained in particular in the conditions when
      uterine contractions and maternal and fetal ectopic beats occurred. On the real
      data, all three methods obtained very high performances, with the QIO-based
      method proving slightly better than the other two (ICAQIO-based: 99.38%, QIO
      based: 99.76%, ICA-based: 99.37%). The findings from this study suggest that the
      proposed method could potentially be applied as a novel algorithm for accurate
      extraction of fECG, especially in critical recording conditions.

PMID- 28509861
TI  - Flexible Antibacterial Coatings.
AB  - This article reviews the present state of the art in the field of flexible
      antibacterial coatings which efficiently kill bacteria on their surfaces.
      Coatings are formed using a reactive magnetron sputtering. The effect of the
      elemental composition and structure of the coating on its antibacterial and
      mechanical properties is explained. The properties of Cr-Cu-O, Al-Cu-N, and Zr-Cu
      N antibacterial coatings are used as examples and described in detail. The
      efficiency of killing of bacteria was tested for the Escherichia coli bacterium.
      The principle of the formation of thick, flexible antibacterial coatings which
      are resistant to cracking under bending is explained. It is shown that magnetron
      sputtering enables production of robust, several-micrometer thick, flexible
      antibacterial coatings for long-term use. The antibacterial coatings produced by
      magnetron sputtering present huge potential for many applications.

PMID- 28509859
TI  - AlCl3.6H2O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone
      Methide Moiety of Celastrol.
AB  - A classical Friedel-Crafts alkylation of different indoles catalyzed by
      AlCl3.6H2O has been developed for a well-known important natural product,
      celastrol, resulting in a series of derivatives for further biological
      evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at
      ambient temperature and reaction time is only 3 h. The product yields range from
      20% to 99%. A reaction mechanism is also proposed, based on our experiment
      results.

PMID- 28509863
TI  - A Fairness Oriented Neighbor-Channel-Aware MAC Protocol for Airborne Sensor
      Networks.
AB  - In airborne sensor networks (ASNs), the media access control (MAC) protocol faces
      a serious unfairness problem due to the traditional protection mechanism of air
      to-air communications among aircraft. Actually, by using the binary exponential
      back-off algorithm at high traffic loads to minimize collisions among users, the
      latest successful node can always benefit from this kind of MAC to obtain channel
      resources. Moreover, when taking the existence of the hidden nodes in ASNs into
      account, the inaccurate traffic load information will further aggravate the
      system's unfairness. In this paper, a neighbor-channel-aware (NCA) protocol is
      proposed to improve the fairness of MAC protocol in ASNs. In the proposal, the
      NCA frame is firstly added and exchanged between neighbor nodes periodically,
      which helps to resolve the inaccurate traffic load information, so as to avoid
      reducing the probability of successful message transmission. Then a traffic
      loading based back-off algorithm is involved to make the neighbor nodes
      cooperatively adjust the inter-frame space (IFS) interval to further reduce the
      unfairness. The simulation results show that, the proposed MAC protocol can
      guarantee the satisfied fairness, simultaneously avoiding heavy network overloads
      to protect key messages' successful transmissions in ASNs.

PMID- 28509862
TI  - Cation, Anion and Ion-Pair Complexes with a G-3 Poly(ethylene imine) Dendrimer in
      Aqueous Solution.
AB  - The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability,
      being able to bind metal cations, anions and ion-pairs. The equilibrium constants
      for the formation of metal (Cu2+, Zn2+), anion (SO42-) and ion-pair (Cu2+/SO42-)
      complexes were determined in 0.1 M Me4NCl aqueous solution at 298.1 +/- 0.1 K by
      means of potentiometric titrations. Thanks to its dendrimeric nature, L2 can form
      highly nucleated metal complexes, such as Cu5L210+ and Zn4L28+, in successive and
      well-defined complexation steps. Protonated forms of L2 give rise to relatively
      weak anion complexes with SO42-, but the addition of Cu2+ significantly enhances
      the binding ability of the ligand toward this anion below pH 9. In more alkaline
      solutions, an opposite trend is observed. The coordination properties of L2 are
      discussed with the support of modelling calculations. According to results, L2 is
      a promising molecule for the preparation of solid supported materials for the
      recovery of cations and anions from aqueous media and/or for applications in
      heterogeneous catalysis.

PMID- 28509857
TI  - Microbial Diversity in Extreme Marine Habitats and Their Biomolecules.
AB  - Extreme marine environments have been the subject of many studies and scientific
      publications. For many years, these environmental niches, which are characterized
      by high or low temperatures, high-pressure, low pH, high salt concentrations and
      also two or more extreme parameters in combination, have been thought to be
      incompatible to any life forms. Thanks to new technologies such as metagenomics,
      it is now possible to detect life in most extreme environments. Starting from the
      discovery of deep sea hydrothermal vents up to the study of marine biodiversity,
      new microorganisms have been identified, and their potential uses in several
      applied fields have been outlined. Thermophile, halophile, alkalophile,
      psychrophile, piezophile and polyextremophile microorganisms have been isolated
      from these marine environments; they proliferate thanks to adaptation strategies
      involving diverse cellular metabolic mechanisms. Therefore, a vast number of new
      biomolecules such as enzymes, polymers and osmolytes from the inhabitant
      microbial community of the sea have been studied, and there is a growing interest
      in the potential returns of several industrial production processes concerning
      the pharmaceutical, medical, environmental and food fields.

PMID- 28509864
TI  - A Probabilistically Weakly Secure Network Coding Scheme in Multipath Routing for
      WSNs.
AB  - In wireless sensor networks, nodes are mostly deployed in unsupervised areas and
      are vulnerable to a variety of attacks. Therefore, data security is a vital
      aspect to be considered. However, due to the limited computation capability and
      memory of sensor nodes, it is difficult to perform the complex encryption
      algorithm, as well as the key distribution and management algorithm. Toward this
      end, a low-complexity algorithm for security in wireless sensor networks is of
      significant importance. In this article, a weakly secure network coding based
      multipath routing scheme is proposed, which can guarantee the data
      confidentiality in transmission probabilistically, and can improve the energy
      efficiency in the meantime. Then the simulations of the probability of
      transmission being secure are performed. The results show that with the increase
      of the number of hops k, the probability of transmission being secure suffers
      from a rapid decrease. On the contrary, with the increase of multicast capacity h
      it undergoes a slight growth. Therefore, the weak security can be achieved with
      probability approaching 1 by limiting the number of hops and increasing the
      multicast capacity. Meanwhile, the simulations of energy consumption are
      performed and the comparison between the energy consumption of the scheme in this
      article and the multipath routing scheme without network coding is conducted. The
      results show that by employing network coding, the scheme in this article can
      improve the energy efficiency, and the more packets transmitted, the more energy
      consumption can be reduced.

PMID- 28509865
TI  - Detecting and Classifying Human Touches in a Social Robot Through Acoustic
      Sensing and Machine Learning.
AB  - An important aspect in Human-Robot Interaction is responding to different kinds
      of touch stimuli. To date, several technologies have been explored to determine
      how a touch is perceived by a social robot, usually placing a large number of
      sensors throughout the robot's shell. In this work, we introduce a novel
      approach, where the audio acquired from contact microphones located in the
      robot's shell is processed using machine learning techniques to distinguish
      between different types of touches. The system is able to determine when the
      robot is touched (touch detection), and to ascertain the kind of touch performed
      among a set of possibilities: stroke, tap, slap, and tickle (touch
      classification). This proposal is cost-effective since just a few microphones are
      able to cover the whole robot's shell since a single microphone is enough to
      cover each solid part of the robot. Besides, it is easy to install and configure
      as it just requires a contact surface to attach the microphone to the robot's
      shell and plug it into the robot's computer. Results show the high accuracy
      scores in touch gesture recognition. The testing phase revealed that Logistic
      Model Trees achieved the best performance, with an F-score of 0.81. The dataset
      was built with information from 25 participants performing a total of 1981 touch
      gestures.

PMID- 28509867
TI  - Supporting the Identification of Novel Fragment-Based Positive Allosteric
      Modulators Using a Supervised Molecular Dynamics Approach: A Retrospective
      Analysis Considering the Human A2A Adenosine Receptor as a Key Example.
AB  - Structure-driven fragment-based (SDFB) approaches have provided efficient methods
      for the identification of novel drug candidates. This strategy has been largely
      applied in discovering several pharmacological ligand classes, including enzyme
      inhibitors, receptor antagonists and, more recently, also allosteric (positive
      and negative) modulators. Recently, Siegal and collaborators reported an
      interesting study, performed on a detergent-solubilized StaR adenosine A2A
      receptor, describing the existence of both fragment-like negative allosteric
      modulators (NAMs), and fragment-like positive allosteric modulators (PAMs). From
      this retrospective study, our results suggest that Supervised Molecular Dynamics
      (SuMD) simulations can support, on a reasonable time scale, the identification of
      fragment-like PAMs following their receptor recognition pathways and
      characterizing the possible allosteric binding sites.

PMID- 28509868
TI  - Compact Eucapnic Voluntary Hyperpnoea Apparatus for Exercise-Induced Respiratory
      Disease Detection.
AB  - Eucapnic voluntary hyperpnoea (EVH) challenge provides objective criteria for
      exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB), and
      it was recommended to justify the use of inhaled beta2-agonists by athletes for
      the Olympics. This paper presents the development of a compact and easy-to-use
      EVH apparatus for assessing EIB in human subjects. The compact apparatus has been
      validated on human subjects and the results have been compared to the
      conventional EVH system. Twenty-two swimmers, including eleven healthy subjects
      and eleven subjects who had been physician-diagnosed with asthma, were recruited
      from sport and recreation centers throughout Auckland, New Zealand. Each subject
      performed two EVH challenge tests using the proposed breathing apparatus and the
      conventional Phillips EVH apparatus on separate days, respectively. Forced
      expiratory volume in one second (FEV1) was measured before and after the
      challenges. A reduction in FEV1 of 10% or more was considered positive. Of the
      eleven subjects who were previously diagnosed with asthma, EIB was present in all
      subjects (100%) in the compact EVH group, while it was presented in ten subjects
      (90.91%) in the conventional EVH challenge group. Of the eleven healthy subjects,
      EIB was present in one subject (4.55%) in the compact EVH group, while it was not
      present in the conventional EVH group. Experimental results showed that the
      compact EVH system has potential to become an alternative tool for EIB detection.

PMID- 28509869
TI  - Experimental Approach for the Uncertainty Assessment of 3D Complex Geometry
      Dimensional Measurements Using Computed Tomography at the mm and Sub-mm Scales.
AB  - The dimensional verification of miniaturized components with 3D complex
      geometries is particularly challenging. Computed Tomography (CT) can represent a
      suitable alternative solution to micro metrology tools based on optical and
      tactile techniques. However, the establishment of CT systems' traceability when
      measuring 3D complex geometries is still an open issue. In this work, an
      alternative method for the measurement uncertainty assessment of 3D complex
      geometries by using CT is presented. The method is based on the micro-CT system
      Maximum Permissible Error (MPE) estimation, determined experimentally by using
      several calibrated reference artefacts. The main advantage of the presented
      method is that a previous calibration of the component by a more accurate
      Coordinate Measuring System (CMS) is not needed. In fact, such CMS would still
      hold all the typical limitations of optical and tactile techniques, particularly
      when measuring miniaturized components with complex 3D geometries and their
      inability to measure inner parts. To validate the presented method, the most
      accepted standard currently available for CT sensors, the Verein Deutscher
      Ingenieure/Verband Deutscher Elektrotechniker (VDI/VDE) guideline 2630-2.1 is
      applied. Considering the high number of influence factors in CT and their impact
      on the measuring result, two different techniques for surface extraction are also
      considered to obtain a realistic determination of the influence of data
      processing on uncertainty. The uncertainty assessment of a workpiece used for
      micro mechanical material testing is firstly used to confirm the method, due to
      its feasible calibration by an optical CMS. Secondly, the measurement of a
      miniaturized dental file with 3D complex geometry is carried out. The estimated
      uncertainties are eventually compared with the component's calibration and the
      micro manufacturing tolerances to demonstrate the suitability of the presented CT
      calibration procedure. The 2U/T ratios resulting from the validation workpiece
      are, respectively, 0.27 (VDI) and 0.35 (MPE), by assuring tolerances in the range
      of +/- 20-30 um. For the dental file, the EN < 1 value analysis is favorable in
      the majority of the cases (70.4%) and 2U/T is equal to 0.31 for sub-mm measurands
      (L < 1 mm and tolerance intervals of +/- 40-80 um).

PMID- 28509866
TI  - HDAC8 Prevents Anthrax Lethal Toxin-induced Cell Cycle Arrest through Silencing
      PTEN in Human Monocytic THP-1 Cells.
AB  - Anthrax lethal toxin (LeTx) is a cytotoxic virulence factor that causes cell
      cycle arrest and cell death in various cell types. However, susceptibility to the
      cytotoxic effects varies depending on cell types. In proliferating monocytes,
      LeTx has only transient cytotoxic effects due to activation of the
      phosphoinositide 3-kinase (PI3K)-AKT-mediated adaptive responses. To date, the
      mechanism of LeTx in activating PI3K-AKT signaling axis is unknown. This study
      shows that the histone deacetylase 8 (HDAC8) is involved in activating PI3K-AKT
      signaling axis through down-regulating the phosphatase and tensin homolog 1
      (PTEN) in human monocytic THP-1 cells. The HDAC8-specific activator TM-2-51 and
      inhibitor PCI-34051 enhanced and prevented, respectively, AKT activation and cell
      cycle progression in LeTx-treated cells. Furthermore, HDAC8 induced tri
      methylation of histone H3 lysine 27 (H3K27me3), which is known to suppress PTEN
      expression, through at least in part down-regulating the H3K27me3 eraser Jumonji
      Domain Containing (JMJD) 3. Importantly, the JMJD3-specific inhibitor GSK-J4
      induced AKT activation and protected cell cycle arrest in LeTx-treated cells,
      regardless the presence of HDAC8 activity. Collectively, this study for the first
      time demonstrated that HDAC8 activity determines susceptibility to cell cycle
      arrest induced by LeTx, through regulating the PI3K-PTEN-AKT signaling axis.

PMID- 28509870
TI  - Sound Power Estimation for Beam and Plate Structures Using Polyvinylidene
      Fluoride Films as Sensors.
AB  - The theory for calculation and/or measurement of sound power based on the
      classical velocity-based radiation mode (V-mode) approach is well established for
      planar structures. However, the current V-mode theory is limited in scope in that
      it can only be applied to conventional motion sensors (i.e., accelerometers). In
      this study, in order to estimate the sound power of vibrating beam and plate
      structure by using polyvinylidene fluoride (PVDF) films as sensors, a PVDF-based
      radiation mode (C-mode) approach concept is introduced to determine the sound
      power radiation from the output signals of PVDF films of the vibrating structure.
      The proposed method is a hybrid of vibration measurement and numerical
      calculation of C-modes. The proposed C-mode approach has the following
      advantages: (1) compared to conventional motion sensors, the PVDF films are
      lightweight, flexible, and low-cost; (2) there is no need for special measuring
      environments, since the proposed method does not require the measurement of sound
      fields; (3) In low frequency range (typically with dimensionless frequency kl <
      4), the radiation efficiencies of the C-modes fall off very rapidly with
      increasing mode order, furthermore, the shapes of the C-modes remain almost
      unchanged, which means that the computation load can be significantly reduced due
      to the fact only the first few dominant C-modes are involved in the low frequency
      range. Numerical simulations and experimental investigations were carried out to
      verify the accuracy and efficiency of the proposed method.

PMID- 28509871
TI  - Nutraceutical Value of Citrus Flavanones and Their Implications in Cardiovascular
      Disease.
AB  - Background- Cardiovascular diseases, including myocardial infarction,
      dyslipidaemia and coronary artery pathology, are a major cause of illness and
      death in Western countries. Therefore, identifying effective therapeutic
      approaches and their cellular signalling pathways is a challenging goal for
      medicine. In this regard, several epidemiological studies demonstrate a
      relationship between the intake of flavonoid-rich foods and the reduction of
      cardiovascular risk factors and mortality. In particular, flavonoids present in
      citrus fruits, such as oranges, bergamots, lemons and grapefruit (95% from
      flavanones), are emerging for their considerable nutraceutical value. Methods- In
      this review an examination of literature was performed while considering both
      epidemiological, clinical and pre-clinical evidence supporting the beneficial
      role of the flavanone class. We evaluated studies in which citrus fruit juices or
      single flavanone administration and cardiovascular risk factors were analysed; to
      identify these studies, an electronic search was conducted in PUBMED for papers
      fulfilling these criteria and written in English. Results- In addition to
      epidemiological evidence and clinical studies demonstrating that fruits in the
      Citrus genus significantly reduce the incidence of cardiovascular disease risk,
      pre-clinical investigations highlight cellular and subcellular targets that are
      responsible for these beneficial effects. There has been special attention on
      evaluating intracellular pathways involved in direct cardiovascular and
      cardiometabolic effects mediated by naringenin, hesperetin and eriodictyol or
      their glycosylated derivatives. Conclusions- Although some mechanisms of action
      remain unclear and bioavailability problems remain to be solved, the current
      evidence supports the use of a nutraceutical approach with citrus fruits to
      prevent and cure several aspects of cardiovascular disease.

PMID- 28509872
TI  - Synthesis of Pyrimethanil-Loaded Mesoporous Silica Nanoparticles and Its
      Distribution and Dissipation in Cucumber Plants.
AB  - Mesoporous silica nanoparticles are used as pesticide carries in plants, which
      has been considered as a novel method to reduce the indiscriminate use of
      conventional pesticides. In the present work, mesoporous silica nanoparticles
      with particle diameters of 200-300 nm were synthesized in order to obtain
      pyrimethanil-loaded nanoparticles. The microstructure of the nanoparticles was
      observed by scanning electron microscopy. The loading content of pyrimethanil
      loaded nanoparticles was investigated. After treatment on cucumber leaves, the
      concentrations of pyrimethanil were determined in different parts of cucumber
      over a period of 48 days using high performance liquid chromatography tandem mass
      spectrometry. It was shown that the pyrimethanil-loaded mesoporous silica
      nanoparticles might be more conducive to acropetal, rather than basipetal,
      uptake, and the dosage had almost no effect on the distribution and dissipation
      rate in cucumber plants. The application of the pesticide-loaded nanoparticles in
      leaves had a low risk of pyrimethanil accumulating in the edible part of the
      plant.

PMID- 28509873
TI  - Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil
      Constituents.
AB  - Several constituents of essential oils have been shown to be active against
      pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in
      vitro action of ten compounds present in essential oils against Leishmania
      amazonensis promastigotes. With the exception of p-cymene, all evaluated
      compounds presented leishmanicidal activity, exhibiting IC50 between 25.4 and
      568.1 MUg mL-1. Compounds with the best leishmanicidal activity presented a
      phenolic moiety (IC50 between 25.4 and 82.9 MUg mL-1). Alicyclic alcohols ((-)
      menthol and isoborneol) and ketones ((-)-carvone) promoted similar activity
      against the parasite (IC50 between 190.2 and 198.9 MUg mL-1). Most of the
      compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure
      activity relationship of these compounds showed the importance of the phenolic
      structure for the biological action against the promastigote forms of the
      parasite.

PMID- 28509874
TI  - Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate
      Derivatives.
AB  - Sugars with heteroatoms other than oxygen have attained considerable importance
      in glycobiology and in drug design since they are often more stable in blood
      plasma due to their resistance to enzymes, such as glycosidases, phosphorylases
      and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur
      forms thio-sugars, which are potentially useful for the treatment of diabetes and
      some bacterial and viral infections. Here, we evaluated the antibacterial
      activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds
      was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative
      Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate
      derivatives were most effective against tubercle bacilli, with as many as five
      compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20,
      aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 <= 50
      uM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to
      inhibit the growth of E. coli at concentrations below 1 mM, and one of them,
      aminothiadiazole 23, inhibited the growth of S. aureus at a concentration <=1 mM.
      The five compounds affecting the growth of mycobacteria were either
      thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these
      compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb
      deposited within human macrophages. However, three of the five selected compounds
      (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at
      micromolar concentrations. The selected thio-sugars are very promising compounds,
      thus making them candidates for further modifications that would decrease their
      cytotoxicity against eukaryotic cells without affecting their antimycobacterial
      potential.

PMID- 28509875
TI  - In Silico Analysis of Epitope-Based Vaccine Candidates against Hepatitis B Virus
      Polymerase Protein.
AB  - Hepatitis B virus (HBV) infection has persisted as a major public health problem
      due to the lack of an effective treatment for those chronically infected.
      Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal
      for viral eradication. In this research, a computational approach was employed to
      predict suitable HBV polymerase targeting multi-peptides for vaccine candidate
      selection. We then performed in-depth computational analysis to evaluate the
      predicted epitopes' immunogenicity, conservation, population coverage, and
      toxicity. Lastly, molecular docking and MHC-peptide complex stabilization assay
      were utilized to determine the binding energy and affinity of epitopes to the HLA
      A0201 molecule. Criteria-based analysis provided four predicted epitopes,
      RVTGGVFLV, VSIPWTHKV, YMDDVVLGA and HLYSHPIIL. Assay results indicated the lowest
      binding energy and high affinity to the HLA-A0201 molecule for epitopes VSIPWTHKV
      and YMDDVVLGA and epitopes RVTGGVFLV and VSIPWTHKV, respectively. Regions 307 to
      320 and 377 to 387 were considered to have the highest probability to be involved
      in B cell epitopes. The T cell and B cell epitopes identified in this study are
      promising targets for an epitope-focused, peptide-based HBV vaccine, and provide
      insight into HBV-induced immune response.

PMID- 28509876
TI  - Optimization of EPS Production and Characterization by a Halophilic Bacterium,
      Kocuria rosea ZJUQH from Chaka Salt Lake with Response Surface Methodology.
AB  - With the rising awareness of microbial exopolysaccharides (EPSs) application in
      various fields, halophilic microorganisms which produce EPSs have received broad
      attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined
      to be a moderate halobacterium on account of its successful adaption to the
      environment containing 10% NaCl. The optimal combination of fermentation medium
      compositions on EPS production was studied. In this work, a fractional factorial
      design was adopted to investigate the significant factors that affected EPS
      production. The factors of KCl and MgSO4 were found to have a profound impact on
      EPS production. We utilized central composite design and response surface
      methodology to derive a statistical model for optimizing the submerged culture
      medium composition. Judging from these experimental results, the optimum culture
      medium for producing EPSs was composed of 0.50% casein hydrolysate, 1.00% sodium
      citrate, 0.30% yeast extract, 0.50% KCl, 0.50% peptone, and 5.80% MgSO4 (initial
      pH 7.0). The maximal EPS was 48.01 g/L, which is close to the predicted value
      (50.39 g/L). In the validation experiment, the highest concentration of 70.64 g/L
      EPSs was obtained after 120 h under the optimized culture medium in a 5-L
      bioreactor. EPS from this bacterium was also characterized by differential
      scanning calorimetry (DSC) and Fourier transform infrared analysis (FT-IR). The
      findings in this study imply that Kocuria rosea ZJUQH has great potential to be
      exploited as a source of EPSs utilized in food, the pharmaceutical and
      agriculture industry, and in the biotreatment of hypersaline environments.

PMID- 28509877
TI  - Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6+CD4+ T
      Cells.
AB  - Chemokine receptor type 6 (CCR6)+CD4+ T cells are preferentially infected and
      depleted during HIV disease progression, but are preserved in non-progressors.
      CCR6 is expressed on a heterogeneous population of memory CD4+ T cells that are
      critical to mucosal immunity. Preferential infection of these cells is
      associated, in part, with high surface expression of CCR5, CXCR4, and
      alpha4beta7. In addition, CCR6+CD4+ T cells harbor elevated levels of integrated
      viral DNA and high levels of proliferation markers. We have previously shown that
      the CCR6 ligands MIP-3alpha and human beta defensins inhibit HIV replication. The
      inhibition required CCR6 and the induction of APOBEC3G. Here, we further
      characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by
      human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional
      induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2
      (ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We
      demonstrate that human beta defensin 2 selectively protects primary CCR6+CD4+ T
      cells infected with HIV-1. The selective protection of CCR6+CD4+ T cell subsets
      may be critical in maintaining mucosal immune function and preventing disease
      progression.

PMID- 28509879
TI  - Quality over Quantity: Contribution of Urban Green Space to Neighborhood
      Satisfaction.
AB  - There is increasing evidence that the quality of green space significantly
      contributes to neighborhood satisfaction and well-being, independent of the mere
      amount of green space. In this paper, we examined residents' perceptions of the
      quality and beneficial affordances of green space in relation to objectively
      assessed accessibility and usability. We used data from a survey in two
      neighborhoods (N = 223) of a medium-sized city in the Netherlands, which were
      similar in the amount of green space and other physical and socio-demographic
      characteristics, but differed in the availability of accessible and usable green
      spaces. Results show that residents of the neighborhood with a higher
      availability of accessible and usable green spaces were more satisfied with their
      neighborhood. This difference was statistically mediated by the higher level of
      perceived green space quality. Neighborhood satisfaction was significantly
      positively related to well-being. However, residents of the two neighborhoods did
      not differ in self-reported well-being and beneficial affordances of green space.
      These analyses contribute to a further understanding of how the accessibility and
      usability of green spaces may increase people's neighborhood satisfaction. It
      highlights the importance of perceived quality in addition to the amount of green
      space when examining the beneficial effects of green space.

PMID- 28509880
TI  - Analysis of Different Approaches for the Selection of Reference Genes in RT-qPCR
      Experiments: A Case Study in Skeletal Muscle of Growing Mice.
AB  - The reliability of reverse transcription-quantitative PCR (RT-qPCR) results in
      gene expression studies depends on the approaches used to account for non
      biological variations. In order to find a proper normalization strategy for the
      study of genes related to growth hormone signaling in skeletal muscle of growing
      mice, nine unrelated genes were evaluated as internal controls. According to the
      most used algorithms-geNorm, the Comparative DeltaCq method, NormFinder and
      BestKeeper-GSK3B, YWHAZ, RPL13A and RN18S were found as the most stable. However,
      the relative expression levels of eight of the potential reference genes assessed
      decreased with age in cDNA samples obtained from the same amount of total RNA. In
      a different approach to analyze this apparent discrepancy, experiments were
      performed with cDNA obtained from equal amounts of purified mRNA. Since the
      decline was still observed, the hypothesis of an age-related change in mRNA to
      total RNA ratio that could account for the systematic decrease was rejected.
      Differences among experimental groups could be due to a substantial increase with
      age in highly expressed mRNAs, which would bias the quantitation of the remaining
      genes. Consequently, those reference genes reflecting this dilution effect, which
      would have been discarded considering their variable relative expression levels,
      arose as suitable internal controls.

PMID- 28509878
TI  - Antigenic and Biological Characterization of ORF2-6 Variants at Early Times
      Following PRRSV Infection.
AB  - Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV)
      challenges efforts to develop effective and broadly acting vaccines. Although
      genetic variation in PRRSV has been extensively documented, the effects of this
      variation on virus phenotype are less well understood. In the present study,
      PRRSV open reading frame (ORF)2-6 variants predominant during the first six weeks
      following experimental infection were characterized for antigenic and replication
      phenotype. There was limited genetic variation during these early times after
      infection; however, distinct ORF2-6 haplotypes that differed from the NVSL97-7895
      inoculum were identified in each of the five pigs examined. Chimeric viruses
      containing all or part of predominant ORF2-6 haplotypes were constructed and
      tested in virus neutralization and in vitro replication assays. In two pigs,
      genetic variation in ORF2-6 resulted in increased resistance to neutralization by
      autologous sera. Mapping studies indicated that variation in either ORF2-4 or
      ORF5-6 could confer increased neutralization resistance, but there was no single
      amino acid substitution that was predictive of neutralization phenotype. Detailed
      analyses of the early steps in PRRSV replication in the presence and absence of
      neutralizing antibody revealed both significant inhibition of virion attachment
      and, independently, a significant delay in the appearance of newly synthesized
      viral RNA. In all pigs, genetic variation in ORF2-6 also resulted in significant
      reduction in infectivity on MARC-145 cells, suggesting variation in ORF2-6 may
      also be important for virus replication in vivo. Together, these data reveal that
      variation appearing early after infection, though limited, alters important virus
      phenotypes and contributes to antigenic and biologic diversity of PRRSV.

PMID- 28509883
TI  - Deposition of Visible Light-Active C-Doped Titania Films via Magnetron Sputtering
      Using CO2 as a Source of Carbon.
AB  - Doping of titanium dioxide with p-block elements is typically described as an
      efficient pathway for the enhancement of photocatalytic activity. However, the
      properties of the doped titania films depend greatly on the production method,
      source of doping, type of substrate, etc. The present work describes the use of
      pulsed direct current (pDC) magnetron sputtering for the deposition of carbon
      doped titania coatings, using CO2 as the source of carbon; ratios of O2/CO2 were
      varied through variations of CO2 flow rates and oxygen flow control setpoints.
      Additionally, undoped Titanium dioxide (TiO2) coatings were prepared under
      identical deposition conditions for comparison purposes. Coatings were post
      deposition annealed at 873 K and analysed with scanning electron microscopy
      (SEM), X-ray diffreaction (XRD), atomic force microscopy (AFM), and X-ray
      photoelectron spectroscopy (XPS). The photocatalytic properties of the thin films
      were evaluated under ultraviolet (UV) and visible light irradiation using
      methylene blue and stearic acid decomposition tests. Photoinduced hydrophilicity
      was assessed through measurements of the water contact angle under UV and visible
      light irradiation. It was found that, though C-doping resulted in improved dye
      degradation compared to undoped TiO2, the UV-induced photoactivity of Carbon
      doped (C-doped) photocatalysts was lower for both model pollutants used.

PMID- 28509882
TI  - Emerging Evidence on Neutrophil Motility Supporting Its Usefulness to Define
      Vitamin C Intake Requirements.
AB  - Establishing intake recommendations for vitamin C remains a challenge, as no
      suitable functional parameter has yet been agreed upon. In this report, we review
      the emerging evidence on neutrophil motility as a possible marker of vitamin C
      requirements and put the results in perspective with other approaches. A recent
      in vitro study showed that adequate levels of vitamin C were needed for this
      function to work optimally when measured as chemotaxis and chemokinesis. In a
      human study, neutrophil motility was optimal at intakes >=250 mg/day.
      Interestingly, a Cochrane review showed a significant reduction in the duration
      of episodes of common cold with regular vitamin C intakes in a similar range.
      Additionally, it was shown that at a plasma level of 75 umol/L, which is reached
      with vitamin C intakes >=200 mg/day, incidences of cardiovascular disease were
      lowest. This evidence would suggest that daily intakes of 200 mg vitamin C might
      be advisable for the general adult population, which can be achieved by means of
      a diverse diet. However, additional studies are warranted to investigate the
      usefulness of neutrophil motility as a marker of vitamin C requirements.

PMID- 28509884
TI  - One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and
      Mechanistic Study.
AB  - A novel one-flask synthetic method was developed in which 5-aminopyrazoles were
      reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane
      was then added to perform heterocyclization to produce the corresponding
      pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus
      involved Vilsmeier amidination, imination reactions, and the sequential
      intermolecular heterocyclization. To study the reaction mechanism, a series of 4
      formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were
      conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5
      yl-formamidine, were prepared and successfully converted into pyrazolo[3,4
      d]pyrimidines. The experiments demonstrated that the reaction intermediates were
      the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5
      yl)formamidines. The rate of the reaction could be described as being
      proportional to the reactivity of amine reactants during intermolecular
      heterocyclization, especially when hexamethyldisilazane was used.

PMID- 28509881
TI  - dFmr1 Plays Roles in Small RNA Pathways of Drosophila melanogaster.
AB  - Fragile-X syndrome is the most common form of inherited mental retardation
      accompanied by other phenotypes, including macroorchidism. The disorder
      originates with mutations in the Fmr1 gene coding for the FMRP protein, which,
      with its paralogs FXR1 and FXR2, constitute a well-conserved family of RNA
      binding proteins. Drosophila melanogaster is a good model for the syndrome
      because it has a unique fragile X-related gene: dFmr1. Recently, in addition to
      its confirmed role in the miRNA pathway, a function for dFmr1 in the piRNA
      pathway, operating in Drosophila gonads, has been established. In this review we
      report a summary of the piRNA pathways occurring in gonads with a special
      emphasis on the relationship between the piRNA genes and the crystal-Stellate
      system; we also analyze the roles of dFmr1 in the Drosophila gonads, exploring
      their genetic and biochemical interactions to reveal some unexpected connections.

PMID- 28509885
TI  - The Role of Phytochemicals in the Inflammatory Phase of Wound Healing.
AB  - Historically, plant-based products have been the basis of medicine since before
      the advent of modern Western medicine. Wound dressings made of honey, curcumin
      and other phytochemical-rich compounds have been traditionally used. Recently,
      the mechanisms behind many of these traditional therapies have come to light. In
      this review, we show that in the context of wound healing, there is a global
      theme of anti-inflammatory and antioxidant phytochemicals in traditional
      medicine. Although promising, we discuss the limitations of using some of these
      phytochemicals in order to warrant more research, ideally in randomized clinical
      trial settings.

PMID- 28509886
TI  - An Improved DOA Estimation Approach Using Coarray Interpolation and Matrix
      Denoising.
AB  - Co-prime arrays can estimate the directions of arrival (DOAs) of O ( M N )
      sources with O ( M + N ) sensors, and are convenient to analyze due to their
      closed-form expression for the locations of virtual lags. However, the number of
      degrees of freedom is limited due to the existence of holes in difference
      coarrays if subspace-based algorithms such as the spatial smoothing multiple
      signal classification (MUSIC) algorithm are utilized. To address this issue,
      techniques such as positive definite Toeplitz completion and array interpolation
      have been proposed in the literature. Another factor that compromises the
      accuracy of DOA estimation is the limitation of the number of snapshots. Coarray
      based processing is particularly sensitive to the discrepancy between the sample
      covariance matrix and the ideal covariance matrix due to the finite number of
      snapshots. In this paper, coarray interpolation based on matrix completion (MC)
      followed by a denoising operation is proposed to detect more sources with a
      higher accuracy. The effectiveness of the proposed method is based on the
      capability of MC to fill in holes in the virtual sensors and that of MC denoising
      operation to reduce the perturbation in the sample covariance matrix. The results
      of numerical simulations verify the superiority of the proposed approach.

PMID- 28509888
TI  - Cardiac Contractility Modulation: A Technical Guide for Device Implantation.
AB  - This article provides a technical description of common implant practice for
      delivery of cardiac contractility modulation (CCM) therapy to heart failure
      patients. As of September 2016, the authors of this article collectively have
      been involved with more than 400 system implantations in five medical centers,
      beginning with the advent of CCM therapy approximately 12 years ago. CCM therapy
      has been evaluated in a variety of studies, and was shown to be safe and
      effective and of benefit to patient quality of life and exercise capacity. As the
      use of CCM therapy continuously expands among medical centers in Europe, this
      article describes the technical and practical aspects of the implant procedure,
      and additional special technical cases based on our cumulative experience.

PMID- 28509889
TI  - The Role of Nitrates in the Management of Stable Ischemic Heart Disease: A Review
      of the Current Evidence and Guidelines.
AB  - Coronary artery disease is the leading cause of mortality in the United States
      and can result in significant morbidity. In particular, stable ischemic heart
      disease (SIHD) is a condition that affects nearly 9 million individuals in the
      United States alone, with substantial annual health care costs related to
      recurrent medical visits and chronic disease management. Nitrates form a
      cornerstone of SIHD management by reducing myocardial oxygen consumption and
      increasing exercise capacity by several mechanisms, including increasing
      epicardial blood flow through vasodilation and decreased vascular resistance,
      blunting coronary steal, and reducing preload. Yet the role of nitrates may be
      underappreciated in clinical practice and their utilization may be limited due to
      concerns of tolerance to treatment, a lack of randomized data validating their
      ability to prevent adverse cardiovascular events, and the pervasive use of
      percutaneous interventions without robust attempts at implementing optimal
      medical therapy. In this review, we discuss both the recent
      ACC/AHA/ACP/AATS/PCNA/SCAI/STS and European Society of Cardiology guidelines,
      with a particular focus on indications, contraindications, and future directions
      of nitrate therapy in SIHD.

PMID- 28509890
TI  - Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With
      Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial
      Hypercholesterolemia.
AB  - Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant
      disorder manifested by high concentrations of total cholesterol and low-density
      lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite
      conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in
      patients with HoFH; these patients are considered to be at high risk for
      cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action
      were approved by the US Food and Drug Administration for the treatment of HoFH:
      lomitapide mesylate and mipomersen. Both of these treatments reduce total
      cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol,
      apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes
      the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases
      of HoFH.

PMID- 28509887
TI  - Predictors of Segmented School Day Physical Activity and Sedentary Time in
      Children from a Northwest England Low-Income Community.
AB  - BACKGROUND: Schools have been identified as important settings for health
      promotion through physical activity participation, particularly as children are
      insufficiently active for health. The aim of this study was to investigate the
      child and school-level influences on children's physical activity levels and
      sedentary time during school hours in a sample of children from a low-income
      community; Methods: One hundred and eighty-six children (110 boys) aged 9-10
      years wore accelerometers for 7 days, with 169 meeting the inclusion criteria of
      16 h?day-1 for a minimum of three week days. Multilevel prediction models were
      constructed to identify significant predictors of sedentary time, light, and
      moderate to vigorous physical activity during school hour segments. Child-level
      predictors (sex, weight status, maturity offset, cardiorespiratory fitness,
      physical activity self-efficacy, physical activity enjoyment) and school-level
      predictors (number on roll, playground area, provision score) were entered into
      the models; Results: Maturity offset, fitness, weight status, waist circumference
      to-height ratio, sedentary time, moderate to vigorous physical activity, number
      of children on roll and playground area significantly predicted physical activity
      and sedentary time; Conclusions: Research should move towards considering context
      specific physical activity and its correlates to better inform intervention
      strategies.

PMID- 28509891
TI  - Spontaneous Coronary Artery Dissection: A Review of Pathogenesis, Presentations,
      Treatment, and Outcomes.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary
      syndromes and sudden cardiac death. The epidemiology, pathogenesis, and optimal
      approaches to diagnosis and management are poorly understood. Additionally, SCAD
      as a syndrome is commonly under-recognized and its prognosis is not well studied.
      Guidelines on management of SCAD have not yet been established. We present three
      cases of SCAD that varied in their clinical presentation and describe the
      different management strategies utilized. This is followed by a review of the
      clinical features, epidemiology, prognosis, and potential treatment strategies
      for patients presenting with SCAD.

PMID- 28509892
TI  - Arrhythmogenic Right Ventricular Dysplasia: An Under-recognized Form of Inherited
      Cardiomyopathy.
AB  - We report a case of arrhythmogenic right ventricular cardiomyopathy/dysplasia
      (ARVD) in order to evaluate the course of an under-recognized form of
      cardiomyopathy with a vast array of clinical manifestations. The patient is a 49
      year-old white woman transferred from an outside hospital due to dyspnea and
      persistent hypoxia. She had a pertinent family history that included a sister who
      died suddenly in her 30s from unexplained heart failure. Initial work-up for
      hypoxia was unrevealing. Transthoracic echocardiography revealed isolated right
      ventricular dysfunction with dilation and multiple trabeculations. Further
      investigation, including cardiac computed tomography and magnetic resonance
      imaging, revealed fatty infiltration into the right ventricular wall suggestive
      of ARVD.

PMID- 28509893
TI  - Spontaneous Coronary Artery Dissection: Insights From Histology and Optical
      Coherence Tomography.
AB  - Spontaneous coronary artery dissection (SCAD) is a well-known but infrequent
      cause of acute coronary syndrome (ACS), and often goes unrecognized. Although
      management of SCAD is, at times, controversial, when a patient presents with ACS,
      percutaneous coronary intervention (PCI) is frequently necessary. We present a
      patient with ST-segment elevation myocardial infarction (STEMI) with SCAD that
      illustrates two important points: use of intracoronary optical coherence
      tomography to guide PCI, and histologic assessment to provide a unique insight
      into the etiology of SCAD. Following the case, we briefly review the important
      aspects of the pathophysiology, epidemiology, diagnosis, and interventional
      management of SCAD.

PMID- 28509894
TI  - Swallowing-induced Supraventricular Tachyarrhythmia.
AB  - Swallowing-induced supraventricular tachyarrhythmia is an extremely rare entity
      with unclear pathophysiology. A 55-year-old man presented with a 2-year history
      of worsening presyncopal symptoms triggered only by drinking liquids of any
      temperature. Results of a physical examination were unremarkable except for
      reproducible atrial tachycardias to 180 to 210 beats/minute documented on rhythm
      strips when the patient was given water to drink. He underwent radiofrequency
      ablation with complete resolution of symptoms. We reviewed all 43 published cases
      of swallowing-induced supraventricular tachyarrhythmia in the English-language
      medical literature. We found only one other reported case induced only by
      drinking liquids. Radiofrequency ablation appears to be the treatment of choice.

PMID- 28509896
TI  - Inferring personal economic status from social network location.
AB  - It is commonly believed that patterns of social ties affect individuals' economic
      status. Here we translate this concept into an operational definition at the
      network level, which allows us to infer the economic well-being of individuals
      through a measure of their location and influence in the social network. We
      analyse two large-scale sources: telecommunications and financial data of a whole
      country's population. Our results show that an individual's location, measured as
      the optimal collective influence to the structural integrity of the social
      network, is highly correlated with personal economic status. The observed social
      network patterns of influence mimic the patterns of economic inequality. For
      pragmatic use and validation, we carry out a marketing campaign that shows a
      threefold increase in response rate by targeting individuals identified by our
      social network metrics as compared to random targeting. Our strategy can also be
      useful in maximizing the effects of large-scale economic stimulus policies.

PMID- 28509895
TI  - [Chronic Malnutrition among Children under Five in Peru: A Spatial Analysis of
      Nutritional Data, 2010-2016].
AB  - OBJECTIVE: Peru has implemented various strategies seeking to improve nutritional
      indicators in children under five years old. However, high prevalence of
      malnutrition in some regions still remains. The aim of this study was to assess
      changes in regional prevalence and to determine the presence of district
      conglomerates with a high prevalence of chronic childhood malnutrition (CCM) in
      2010 and 2016. METHODS: A comparative descriptive analysis by regions and a
      district-level spatial analysis were conducted employing indicators reported by
      the Nutritional Status Information System. RESULTS: 23.9% (561.090/2.343.806)
      children under five years evaluated in Peru during 2010 and 18.0%
      (394.049/2.193.268) evaluated during 2016 were chronic malnutrition (reduction of
      5.9 percentage points). We identified a decline of 7.6 percent points in rural
      areas and the persistence of prevalence above 30% in only one region
      (Huancavelica). The spatial analysis identified clusters of districts with high
      prevalence in 20% (379/1834) of Peruvian districts in 2010, and 17.2% (316/1834)
      of those in 2016, which are mainly spread across the sierra and jungle regions..
      CONCLUSIONS: Peru has made significant progress in reducing stunting in children.
      Nevertheless, it still represents a health problem due to high prevalence in the
      sierra region, as well as expansion to jungle districts in 2016.

PMID- 28509897
TI  - Disambiguation of patent inventors and assignees using high-resolution
      geolocation data.
AB  - Patent data represent a significant source of information on innovation,
      knowledge production, and the evolution of technology through networks of
      citations, co-invention and co-assignment. A major obstacle to extracting useful
      information from this data is the problem of name disambiguation: linking
      alternate spellings of individuals or institutions to a single identifier to
      uniquely determine the parties involved in knowledge production and diffusion. In
      this paper, we describe a new algorithm that uses high-resolution geolocation to
      disambiguate both inventors and assignees on about 8.5 million patents found in
      the European Patent Office (EPO), under the Patent Cooperation Treaty (PCT), and
      in the US Patent and Trademark Office (USPTO). We show this disambiguation is
      consistent with a number of ground-truth benchmarks of both assignees and
      inventors, significantly outperforming the use of undisambiguated names to
      identify unique entities. A significant benefit of this work is the high quality
      assignee disambiguation with coverage across the world coupled with an inventor
      disambiguation (that is competitive with other state of the art approaches) in
      multiple patent offices.

PMID- 28509898
TI  - Modern pollen data from the Canadian Arctic, 1972-1973.
AB  - This data descriptor reports results of a 1972-73 baseline study of modern pollen
      deposition in the Canadian Arctic to originally aid interpretation of Holocene
      pollen diagrams from that region, especially focussed on the arctic tree-line.
      The data set is geographically unique due to its extent, and allows the
      assessment of the effects of modern climate change on northern ecosystems,
      including fluctuations of the a arctic tree-line. Repeated sampling was conducted
      along an interior transect at 29 sites from the Boreal Forest to the High Arctic,
      with five additional coastal sites covering a total distance of 3,200 km. Static
      pollen samplers captured both local pollen and long-distance pollen wind-blown
      from the Boreal Forest. Moss and lichen polsters provided multi-year pollen
      fallout to assess the effectiveness of the static pollen samplers. The local
      vegetation was recorded at each site. This descriptor provides information on
      data archived at the World Data Center PANGAEA, which includes spreadsheets
      detailing site and sample information as well as raw and processed pollen data
      obtained on over 500 samples.

PMID- 28509899
TI  - A bioprosthetic ovary created using 3D printed microporous scaffolds restores
      ovarian function in sterilized mice.
AB  - Emerging additive manufacturing techniques enable investigation of the effects of
      pore geometry on cell behavior and function. Here, we 3D print microporous
      hydrogel scaffolds to test how varying pore geometry, accomplished by
      manipulating the advancing angle between printed layers, affects the survival of
      ovarian follicles. 30 degrees  and 60 degrees  scaffolds provide corners that
      surround follicles on multiple sides while 90 degrees  scaffolds have an open
      porosity that limits follicle-scaffold interaction. As the amount of scaffold
      interaction increases, follicle spreading is limited and survival increases.
      Follicle-seeded scaffolds become highly vascularized and ovarian function is
      fully restored when implanted in surgically sterilized mice. Moreover, pups are
      born through natural mating and thrive through maternal lactation. These findings
      present an in vivo functional ovarian implant designed with 3D printing, and
      indicate that scaffold pore architecture is a critical variable in additively
      manufactured scaffold design for functional tissue engineering.

PMID- 28509900
TI  - Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain
      and liver tissues from psychiatric disorders: rethinking the brain-liver axis.
AB  - Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of
      psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF
      pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of
      these proteins in psychiatric disorders is unknown. We sought to determine
      whether expression of these proteins is altered in the brain and peripheral
      tissues from patients with psychiatric disorders. We measured protein expression
      of proBDNF, mature BDNF and BDNF pro-peptide in the parietal cortex, cerebellum,
      liver and spleen from control, major depressive disorder (MDD), schizophrenia
      (SZ) and bipolar disorder (BD) groups. The levels of mature BDNF in the parietal
      cortex from MDD, SZ and BD groups were significantly lower than the control
      group, whereas the levels of BDNF pro-peptide in this area were significantly
      higher than controls. In contrast, the levels of proBDNF and BDNF pro-peptide in
      the cerebellum of MDD, SZ and BD groups were significantly lower than controls.
      Moreover, the levels of mature BDNF from the livers of MDD, SZ and BD groups were
      significantly higher than the control group. The levels of mature BDNF in the
      spleen did not differ among the four groups. Interestingly, there was a negative
      correlation between mature BDNF in the parietal cortex and mature BDNF in the
      liver in all the subjects. These findings suggest that abnormalities in the
      production of mature BDNF and BDNF pro-peptide in the brain and liver might have
      a role in the pathophysiology of psychiatric disorders, indicating a brain-liver
      axis in psychiatric disorders.

PMID- 28509901
TI  - A continuum of genetic liability for minor and major depression.
AB  - The recent success of a large genome-wide association (GWA) study-analysing 130
      620 major depression cases and 347 620 controls-in identifying the first single
      nucleotide polymorphism (SNP) loci robustly associated with major depression in
      Europeans confirms that immense sample sizes are required to identify risk loci
      for depression. Given the phenotypic similarity between major depressive disorder
      (MDD) and the less severe minor depressive disorder (MiDD), we hypothesised that
      broadening the case definition to include MiDD may be an efficient approach to
      increase sample sizes in GWA studies of depression. By analysing two large twin
      pair cohorts, we show that minor depression and major depression lie on a single
      genetic continuum, with major depression being more severe but not aetiologically
      distinct from minor depression. Furthermore, we estimate heritabilities of 37%
      for minor depression, 46% for major depression and 48% for minor or major
      depression in a cohort of older adults (aged 50-92). However, the heritability of
      minor or major depression was estimated at 40% in a cohort of younger adults
      (aged 23-38). Moreover, two robust major depression-risk SNPs nominally
      associated with major depression in our Australian GWA data set produced more
      significant evidence for association with minor or major depression. Hence,
      broadening the case phenotype in GWA studies to include subthreshold definitions,
      such as MiDD, should facilitate the identification of additional genetic risk
      loci for depression.

PMID- 28509902
TI  - A latent genetic subtype of major depression identified by whole-exome genotyping
      data in a Mexican-American cohort.
AB  - Identifying data-driven subtypes of major depressive disorder (MDD) is an
      important topic of psychiatric research. Currently, MDD subtypes are based on
      clinically defined depression symptom patterns. Although a few data-driven
      attempts have been made to identify more homogenous subgroups within MDD, other
      studies have not focused on using human genetic data for MDD subtyping. Here we
      used a computational strategy to identify MDD subtypes based on single-nucleotide
      polymorphism genotyping data from MDD cases and controls using Hamming distance
      and cluster analysis. We examined a cohort of Mexican-American participants from
      Los Angeles, including MDD patients (n=203) and healthy controls (n=196). The
      results in cluster trees indicate that a significant latent subtype exists in the
      Mexican-American MDD group. The individuals in this hidden subtype have increased
      common genetic substrates related to major depression and they also have more
      anxiety and less middle insomnia, depersonalization and derealisation, and
      paranoid symptoms. Advances in this line of research to validate this strategy in
      other patient groups of different ethnicities will have the potential to
      eventually be translated to clinical practice, with the tantalising possibility
      that in the future it may be possible to refine MDD diagnosis based on genetic
      data.

PMID- 28509903
TI  - Gray matter anomalies in pedophiles with and without a history of child sexual
      offending.
AB  - Pedophilia is a psychiatric disorder that is inter-related with but distinct from
      child sexual offending (CSO). Neural alterations reportedly contribute to both
      pedophilia and CSO, but until now, no study has distinguished the brain
      structural anomalies associated with pedophilia from those specifically
      associated with CSO in pedophilic men. Using high-resolution T1-weighted brain
      images and voxel-based morphometry, we analyzed the gray matter (GM) volume of
      the following 219 men recruited at four acquisition sites in Germany: 58
      pedophiles with a history of CSO, 60 pedophiles without any history of CSO and
      101 non-pedophilic, non-offending controls to control for the effects of age,
      education level, verbal IQ, sexual orientation and the acquisition site. Although
      there were no differences in the relative GM volume of the brain specifically
      associated with pedophilia, statistical parametric maps revealed a highly
      significant and CSO-related pattern of above vs below the 'normal' GM volume in
      the right temporal pole, with non-offending pedophiles exhibiting larger volumes
      than offending pedophiles. Moreover, regression analysis revealed that the lower
      GM volume of the dorsomedial prefrontal or anterior cingulate cortex was
      associated with a higher risk of re-offending in pedophilic child molesters. We
      believe our data provide the first evidence that CSO in pedophilia rather than
      pedophilia alone is associated with GM anomalies and thus shed new light on the
      results of previous studies on this topic. These results indicate the need for
      new neurobehavioral theories on pedophilia and CSO and may be potentially useful
      for treatment or prevention approaches that aim to reduce the risk of
      (re)offending in pedophilia.

PMID- 28509905
TI  - Crowdsourced validation of a machine-learning classification system for autism
      and ADHD.
AB  - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder
      (ADHD) together affect >10% of the children in the United States, but
      considerable behavioral overlaps between the two disorders can often complicate
      differential diagnosis. Currently, there is no screening test designed to
      differentiate between the two disorders, and with waiting times from initial
      suspicion to diagnosis upwards of a year, methods to quickly and accurately
      assess risk for these and other developmental disorders are desperately needed.
      In a previous study, we found that four machine-learning algorithms were able to
      accurately (area under the curve (AUC)>0.96) distinguish ASD from ADHD using only
      a small subset of items from the Social Responsiveness Scale (SRS). Here, we
      expand upon our prior work by including a novel crowdsourced data set of
      responses to our predefined top 15 SRS-derived questions from parents of children
      with ASD (n=248) or ADHD (n=174) to improve our model's capability to generalize
      to new, 'real-world' data. By mixing these novel survey data with our initial
      archival sample (n=3417) and performing repeated cross-validation with
      subsampling, we created a classification algorithm that performs with AUC=0.89+/
      0.01 using only 15 questions.

PMID- 28509904
TI  - Immunological effects of behavioral activation with exercise in major depression:
      an exploratory randomized controlled trial.
AB  - Major depression (MD) is associated with peripheral inflammation and increased
      cardiovascular risk. Regular physical exercise can have anti-inflammatory
      effects. The present study examined whether behavioral activation with exercise
      affects inflammatory processes in MD. Ninety-eight patients with MD were randomly
      assigned to cognitive-behavioral therapy (CBT) emphasizing exercise during
      behavioral activation (CBT-E), CBT with pleasurable low-energy activities as an
      active control condition (CBT-C) or a passive waiting list control group (WL).
      Plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10,
      lipopolysaccharide (LPS)-stimulated IL-6 production, and blood immune cell counts
      were analyzed at baseline and weeks 8 (post-behavioral activation) and 16 (post
      treatment). Thirty non-depressed age- and sex-matched controls were included to
      examine potential immunological alterations in MD at baseline. Patients with MD
      exhibited higher levels of CRP, higher neutrophil and monocyte counts, lower IL
      10 levels and reduced LPS-stimulated IL-6 production compared to controls
      (P<0.001-0.045). Multilevel modeling indicated that CBT-E was associated with
      increased anti-inflammatory IL-10 at weeks 8 and 16 compared to CBT-C and WL
      (P=0.004-0.018). CBT-E did not significantly affect other immunological makers in
      the total sample. A subgroup analysis including patients with potentially higher
      cardiovascular risk (CRP ?1 MUg ml-1) indicated that CRP was reduced in CBT-E
      compared to CBT-C (P<0.007) and marginally reduced compared to WL (P<0.085) after
      week 16. The present findings provide new insights into immunological effects of
      behavioral treatments against depression. Behavioral activation in conjunction
      with exercise may have the potential to reverse, in part, immunological
      alterations in MD.

PMID- 28509907
TI  - A database of georeferenced nutrient chemistry data for mountain lakes of the
      Western United States.
AB  - Human activities have increased atmospheric nitrogen and phosphorus deposition
      rates relative to pre-industrial background. In the Western U.S., anthropogenic
      nutrient deposition has increased nutrient concentrations and stimulated algal
      growth in at least some remote mountain lakes. The Georeferenced Lake Nutrient
      Chemistry (GLNC) Database was constructed to create a spatially-extensive lake
      chemistry database needed to assess atmospheric nutrient deposition effects on
      Western U.S. mountain lakes. The database includes nitrogen and phosphorus water
      chemistry data spanning 1964-2015, with 148,336 chemistry results from 51,048
      samples collected across 3,602 lakes in the Western U.S. Data were obtained from
      public databases, government agencies, scientific literature, and researchers,
      and were formatted into a consistent table structure. All data are georeferenced
      to a modified version of the National Hydrography Dataset Plus version 2. The
      database is transparent and reproducible; R code and input files used to format
      data are provided in an appendix. The database will likely be useful to those
      assessing spatial patterns of lake nutrient chemistry associated with atmospheric
      deposition or other environmental stressors.

PMID- 28509906
TI  - Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress
      related metabolic pathways.
AB  - Schizophrenia (SZ) is considered to be a multifactorial brain disorder with
      defects involving many biochemical pathways. Patients with SZ show variable
      responses to current pharmacological treatments of SZ because of the
      heterogeneity of this disorder. Stress has a significant role in the
      pathophysiological pathways and therapeutic responses of SZ. Atypical
      antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic
      pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting
      the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs
      (such as clozapine, risperidone and aripiprazole) on stress, we compared
      neurochemical profile variations in the PFC and hippocampus between rat models of
      chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term
      dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance
      liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach
      and a multicriteria assessment. We identified a number of stress-induced
      biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid,
      allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines
      (PEs), corticosterone and progesterone. Specifically, pathway enrichment and
      correlation analyses suggested that stress induces oxidative damage by disturbing
      the creatine-phosphocreatine circuit and purine pathway, leading to excessive
      membrane breakdown. Moreover, our data suggested that the AAPDs tested partially
      restore stress-induced deficits by increasing the levels of creatine,
      progesterone and PEs. Thus, the present findings provide a theoretical basis for
      the hypothesis that a combined therapy using adenosine triphosphate fuel,
      antioxidants and omega-3 fatty acids as supplements may have synergistic effects
      on the therapeutic outcome following AAPD treatment.

PMID- 28509908
TI  - Microbial contributions to the persistence of coral reefs.
AB  - On contemplating the adaptive capacity of reef organisms to a rapidly changing
      environment, the microbiome offers significant and greatly unrecognised
      potential. Microbial symbionts contribute to the physiology, development,
      immunity and behaviour of their hosts, and can respond very rapidly to changing
      environmental conditions, providing a powerful mechanism for acclimatisation and
      also possibly rapid evolution of coral reef holobionts. Environmentally acquired
      fluctuations in the microbiome can have significant functional consequences for
      the holobiont phenotype upon which selection can act. Environmentally induced
      changes in microbial abundance may be analogous to host gene duplication,
      symbiont switching / shuffling as a result of environmental change can either
      remove or introduce raw genetic material into the holobiont; and horizontal gene
      transfer can facilitate rapid evolution within microbial strains. Vertical
      transmission of symbionts is a key feature of many reef holobionts and this would
      enable environmentally acquired microbial traits to be faithfully passed to
      future generations, ultimately facilitating microbiome-mediated transgenerational
      acclimatisation (MMTA) and potentially even adaptation of reef species in a
      rapidly changing climate. In this commentary, we highlight the capacity and
      mechanisms for MMTA in reef species, propose a modified Price equation as a
      framework for assessing MMTA and recommend future areas of research to better
      understand how microorganisms contribute to the transgenerational acclimatisation
      of reef organisms, which is essential if we are to reliably predict the
      consequences of global change for reef ecosystems.

PMID- 28509909
TI  - Experimental evolution and the dynamics of adaptation and genome evolution in
      microbial populations.
AB  - Evolution is an on-going process, and it can be studied experimentally in
      organisms with rapid generations. My team has maintained 12 populations of
      Escherichia coli in a simple laboratory environment for >25 years and 60 000
      generations. We have quantified the dynamics of adaptation by natural selection,
      seen some of the populations diverge into stably coexisting ecotypes, described
      changes in the bacteria's mutation rate, observed the new ability to exploit a
      previously untapped carbon source, characterized the dynamics of genome evolution
      and used parallel evolution to identify the genetic targets of selection. I
      discuss what the future might hold for this particular experiment, briefly
      highlight some other microbial evolution experiments and suggest how the fields
      of experimental evolution and microbial ecology might intersect going forward.

PMID- 28509911
TI  - A dataset of forest biomass structure for Eurasia.
AB  - The most comprehensive dataset of in situ destructive sampling measurements of
      forest biomass in Eurasia have been compiled from a combination of experiments
      undertaken by the authors and from scientific publications. Biomass is reported
      as four components: live trees (stem, bark, branches, foliage, roots); understory
      (above- and below ground); green forest floor (above- and below ground); and
      coarse woody debris (snags, logs, dead branches of living trees and dead roots),
      consisting of 10,351 unique records of sample plots and 9,613 sample trees from
      ca 1,200 experiments for the period 1930-2014 where there is overlap between
      these two datasets. The dataset also contains other forest stand parameters such
      as tree species composition, average age, tree height, growing stock volume,
      etc., when available. Such a dataset can be used for the development of models of
      biomass structure, biomass extension factors, change detection in biomass
      structure, investigations into biodiversity and species distribution and the
      biodiversity-productivity relationship, as well as the assessment of the carbon
      pool and its dynamics, among many others.

PMID- 28509913
TI  - Optimization of a polydopamine (PD)-based coating method and polydimethylsiloxane
      (PDMS) substrates for improved mouse embryonic stem cell (ESC) pluripotency
      maintenance and cardiac differentiation.
AB  - Myocardiocyte derived from pluripotent stem cells, such as induced pluripotent
      stem cells (iPSCs) and embryonic stem cells (ESCs), is a promising cell source
      for cardiac tissue engineering. Combined with microfluidic technologies, a heart
      on-a-chip is very likely to be developed and function as a platform for high
      throughput drug screening. Polydimethylsiloxane (PDMS) silicone elastomer is a
      widely-used biomaterial for the investigation of cell-substrate interactions and
      biochip fabrication. However, the intrinsic PDMS surface hydrophobicity inhibits
      cell adhesion on the PDMS surface, and PDMS surface modification is required for
      effective cell adhesion. Meanwhile, the formulation of PDMS also affects the
      behaviors of the cells. To fabricate PDMS-based biochips for ESC pluripotency
      maintenance and cardiac differentiation, PDMS surface modification and
      formulation were optimized in this study. We found that a polydopamine (PD) with
      gelatin coating greatly improved the ESC adhesion, proliferation and cardiac
      differentiation on its surface. In addition, different PDMS substrates varied in
      their surface properties, which had different impacts on ESCs, with the 40 : 1
      PDMS substrate being more favorable for ESC adhesion and proliferation as well as
      embryoid body (EB) attachment than the other PDMS substrates. Moreover, the ESC
      pluripotency was best maintained on the 5 : 1 PDMS substrate, while the cardiac
      differentiation of the ESCs was optimal on the 40 : 1 PDMS substrate. Based on
      the optimized coating method and PDMS formulation, biochips with two different
      designs were fabricated and evaluated. Compared to the single channels, the
      multiple channels on the biochips could provide larger areas and accommodate more
      nutrients to support improved ESC pluripotency maintenance and cardiac
      differentiation. These results may contribute to the development of a real heart
      on-a-chip for high-throughput drug screening in the future.

PMID- 28509910
TI  - Convergence of gut microbiotas in the adaptive radiations of African cichlid
      fishes.
AB  - Ecoevolutionary dynamics of the gut microbiota at the macroscale level, that is,
      in across-species comparisons, are largely driven by ecological variables and
      host genotype. The repeated explosive radiations of African cichlid fishes in
      distinct lakes, following a dietary diversification in a context of reduced
      genetic diversity, provide a natural setup to explore convergence, divergence and
      repeatability in patterns of microbiota dynamics as a function of the host diet,
      phylogeny and environment. Here we characterized by 16S rRNA amplicon sequencing
      the gut microbiota of 29 cichlid species from two distinct lakes/radiations
      (Tanganyika and Barombi Mbo) and across a broad dietary and phylogenetic range.
      Within each lake, a significant deviation between a carnivorous and herbivorous
      lifestyle was found. Herbivore species were characterized by an increased
      bacterial taxonomic and functional diversity and converged in key compositional
      and functional community aspects. Despite a significant lake effect on the
      microbiota structure, this process has occurred with remarkable parallels in the
      two lakes. A metabolic signature most likely explains this trend, as indicated by
      a significant enrichment in herbivores/omnivores of bacterial taxa and functions
      associated with fiber degradation and detoxification of plant chemical compounds.
      Overall, compositional and functional aspects of the gut microbiota individually
      and altogether validate and predict main cichlid dietary habits, suggesting a
      fundamental role of gut bacteria in cichlid niche expansion and adaptation.

PMID- 28509912
TI  - A resource on latitudinal and altitudinal clines of ecologically relevant
      phenotypes of the Indian Drosophila.
AB  - The unique geography of the Indian subcontinent has provided diverse natural
      environments for a variety of organisms. In this region, many ecological indices
      such as temperature and humidity vary predictably as a function of both latitude
      and altitude; these environmental parameters significantly affect fundamental
      dynamics of natural populations. Indian drosophilids are diverse in their
      geographic distribution and climate tolerance, possibly as a result of climatic
      adaptation. These associations with environmental parameters are further
      reflected in a large number of clines that have been reported for various fitness
      traits along these geographical ranges. This unique amalgamation of environmental
      variability and genetic diversity make the subcontinent an ecological laboratory
      for studying evolution in action. We assembled data collected over the last 20
      years on the geographical clines for various phenotypic traits in several species
      of drosophilids and present a web-resource on Indian-Drosophila (
      http://www.indian-drosophila.org/). The clinal data on ecologically relevant
      phenotypes of Indian drosophilids will be useful in addressing questions related
      to future challenges in biodiversity and ecosystems in this region.

PMID- 28509916
TI  - Systematic variation of thiophene substituents in photochromic spiropyrans.
AB  - Spiropyrans are notable among different classes of photochromic compounds due to
      their large structural and electronic transformation upon isomerization. In order
      to parlay the electronic differences associated with the two isomeric forms into
      a materials based switch, the spiropyran ultimately requires a covalent
      attachment through a conjugated pathway. In this work a synthetic method was
      developed to incorporate spiropyran (SP) into thiophene based materials. A series
      of compounds with a systematic variation of substituents were synthesized (SP-T,
      SP-T-Br, SP-T-T, SP-T-T-T and SP-T-T-T-T-SP) and their photochromism in both
      polar (methanol) and non-polar (toluene) solvents were studied. These compounds
      showed a systematic variation of photochromic properties.

PMID- 28509917
TI  - Effect of mTHPC-mediated photodynamic therapy on 5-fluorouracil resistant human
      colorectal cancer cells.
AB  - The primary or acquired cancer chemoresistance is a major problem in the
      treatment of cancer patients. It could be overcome by non-overlapping treatment
      regimens such as photodynamic therapy (PDT). PDT is based on the oxidation of
      cellular components which occurs when a light-excited photosensitizer generates
      reactive oxygen species (ROS). In this study the effect of mTHPC mediated PDT
      (mTHPC-PDT) on 5-FU resistant colorectal cancer (CRC) cells HCT116 was
      investigated. The results show that mTHPC-PDT overcomes 5-FU resistance and is
      effective against chemoresistant colorectal carcinoma cells.

PMID- 28509919
TI  - Resistive switching of Sn-doped In2O3/HfO2 core-shell nanowire: geometry
      architecture engineering for nonvolatile memory.
AB  - Core-shell NWs offer an innovative approach to achieve nanoscale metal-insulator
      metal (MIM) heterostructures along the wire radial direction, realizing three
      dimensional geometry architecture rather than planar type thin film devices. This
      work demonstrated the tunable resistive switching characteristics of ITO/HfO2
      core-shell nanowires with controllable shell thicknesses by the atomic layer
      deposition (ALD) process for the first time. Compared to planar HfO2 thin film
      device configuration, ITO/HfO2 core-shell nanowire shows a prominent resistive
      memory behavior, including lower power consumption with a smaller SET voltage of
      ~0.6 V and better switching voltage uniformity with variations (standard
      deviation(sigma)/mean value (MU)) of VSET and VRESET from 0.38 to 0.14 and from
      0.33 to 0.05 for ITO/HfO2 core-shell nanowire and planar HfO2 thin film,
      respectively. In addition, endurance over 103 cycles resulting from the local
      electric field enhancement can be achieved, which is attributed to geometry
      architecture engineering. The concept of geometry architecture engineering
      provides a promising strategy to modify the electric-field distribution for
      solving the non-uniformity issue of future RRAM.

PMID- 28509920
TI  - Insights into chemoselectivity principles in metal oxide affinity chromatography
      using tailored nanocast metal oxide microspheres and mass spectrometry-based
      phosphoproteomics.
AB  - The ability to comprehensively characterize biological samples, including tissues
      and body fluids, opens up new possibilities to diagnose and treat diseases and to
      better understand fundamental biological processes. For this purpose, suitable
      experimental workflows need to be designed. In this context, materials with
      particular chemoselective properties are used for the enrichment of certain
      classes of (bio)molecules. Metal oxides such as titanium dioxide have become the
      materials of choice for the large-scale study of protein phosphorylation in
      phosphoproteomics. Despite their widespread use, the main factors influencing
      their performance (for example, affinity and specificity) are not completely
      understood. This understanding is, however, crucial to develop improved materials
      and methods. Here, we used the nanocasting method to prepare microspheres of
      seven metal oxides with comparable textural properties, allowing an objective
      comparison of the materials and their binding properties. We evaluated these
      materials with samples of different complexity, ranging from synthetic peptides
      to whole cell lysates, using liquid chromatography-tandem mass spectrometry as a
      readout. A set of more than 7000 identified phosphopeptides allowed us to study
      differences between the metal oxide sorbents in detail. Importantly, the
      performance of the affinity materials was found to be mainly correlated with the
      oxides' isoelectric points (IEPs), with the materials that enriched the highest
      number of phosphopeptides having an IEP of around 6. This included the widely
      used TiO2 and ZrO2, but also In2O3 that was not previously known to possess
      affinity to phosphates. This finding supports the conclusion that the IEP has a
      stronger influence than the particular type of metal oxide and contrasts earlier
      reports that compared a limited number of materials with often unknown textural
      properties. Taken together, we introduce new metal oxides suitable for
      phosphopeptide enrichment, provide deeper insight into the properties that affect
      their performance, and offer a strategy to optimize enrichment protocols and
      materials.

PMID- 28509921
TI  - Bright red-emitting pyrene derivatives with a large Stokes shift for nucleus
      staining.
AB  - A highly fluorescent red-emitting pyrene derivative was synthesized and found to
      exhibit a large Stokes shift (lambdaem ~ 610 nm, Deltalambda ~ 130 nm, Deltanu ~
      4597 cm-1). The probe molecule showed remarkable selectivity to stain the nucleus
      in both live and fixed cells, with higher sensitivity than commercial dye DRAQ5.

PMID- 28509922
TI  - Phosphine-catalyzed Friedel-Crafts reaction of naphthols with para-quinone
      methides: expedient access to triarylmethanes.
AB  - We developed a novel phosphine-catalyzed Friedel-Crafts reaction of naphthols
      with para-quinone methides (p-QMs). This reaction provided a promising method for
      the synthesis of triarylmethanes, which widely exist in natural products and in
      molecules which have been shown to have biological and pharmacological activity.

PMID- 28509923
TI  - Enantioselective alkynylation of N-sulfonyl alpha-ketiminoesters via a Friedel
      Crafts alkylation strategy.
AB  - Enantioselective alkynylation of cyclic N-sulfonyl alpha-ketiminoesters with
      terminal alkynes was developed by using an Ni(ClO4)2/(R)-DTBM-Segphos complex as
      a catalyst. A range of propargylic amides bearing quaternary stereocenters were
      afforded in excellent enantioselectivities (up to 97% ee). Theoretical studies
      revealed that this reaction proceeded via a Friedel-Crafts-type reaction pathway.

PMID- 28509918
TI  - Generation and manipulation of hydrogel microcapsules by droplet-based
      microfluidics for mammalian cell culture.
AB  - Hydrogel microcapsules provide miniaturized and biocompatible niches for three
      dimensional (3D) in vitro cell culture. They can be easily generated by droplet
      based microfluidics with tunable size, morphology, and biochemical properties.
      Therefore, microfluidic generation and manipulation of cell-laden microcapsules
      can be used for 3D cell culture to mimic the in vivo environment towards
      applications in tissue engineering and high throughput drug screening. In this
      review of recent advances mainly since 2010, we will first introduce general
      characteristics of droplet-based microfluidic devices for cell encapsulation with
      an emphasis on the fluid dynamics of droplet breakup and internal mixing as they
      directly influence microcapsule's size and structure. We will then discuss two on
      chip manipulation strategies: sorting and extraction from oil into aqueous phase,
      which can be integrated into droplet-based microfluidics and significantly
      improve the qualities of cell-laden hydrogel microcapsules. Finally, we will
      review various applications of hydrogel microencapsulation for 3D in vitro
      culture on cell growth and proliferation, stem cell differentiation, tissue
      development, and co-culture of different types of cells.

PMID- 28509924
TI  - Multilayered intercalation of 1-octanol into Brodie graphite oxide.
AB  - Multilayered intercalation of 1-octanol into the structure of Brodie graphite
      oxide (B-GO) was studied as a function of temperature and pressure. Reversible
      phase transition with the addition/removal of one layer of 1-octanol was found at
      265 K by means of X-ray Diffraction (XRD) and Differential Scanning Calorimetry
      (DSC). The same transition was observed at ambient temperature upon a pressure
      increase above 0.6 GPa. This transition was interpreted as an incongruent melting
      of the low temperature/high pressure B-GO intercalated structure with five layers
      of 1-octanol parallel to GO sheets (L-solvate), resulting in the formation of a
      four-layered structure that is stable under ambient conditions (A-solvate).
      Vacuum heating allows the removal of 1-octanol from the A-solvate layer by layer,
      while distinct sets of (00l) reflections are observed for three-, two-, and one
      layered solvate phases. Step by step removal of the 1-octanol layers results in
      changes of distance between graphene oxide planes by ~4.5 A. This experiment
      proved that both L- and A-solvates are structures with layers of 1-octanol
      parallel to GO planes. Unusual intercalation with up to five distinct layers of 1
      octanol is remarkably different from the behaviour of small alcohol molecules
      (methanol and ethanol), which intercalate B-GO structure with only one layer
      under ambient conditions and a maximum of two layers at lower temperatures or
      higher pressures. The data presented in this study make it possible to rule out a
      change in the orientation of alcohol molecules from parallel to perpendicular to
      the GO planes, as suggested in the 1960s to explain larger expansion of the GO
      lattice due to swelling with larger alcohols.

PMID- 28509925
TI  - Palladium(0)-catalyzed [2 + 2 + 1] cyclization of 1,6-enynes with vinyl bromides:
      a highly diastereoselective synthesis of tetrahydro-1H-cyclopenta[c]furans
      bearing two quaternary carbon centers.
AB  - A new cascade process has been accomplished for the synthesis of tetrahydro-1H
      cyclopenta[c]furans through palladium-catalyzed [2 + 2 + 1] cyclization of 1,6
      enynes with vinyl bromides. Notably, the key feature of this transformation is
      the use of vinyl bromides as the C1 building block. Various functionalized
      tetrahydro-1H-cyclopenta[c]furans bearing two quaternary carbon centers could be
      obtained in good yields with excellent diastereoselectivities.

PMID- 28509927
TI  - Tuning morphological architectures generated through living supramolecular
      assembly of a helical foldamer end-capped with two complementary nucleobases.
AB  - Two appropriately functionalized nucleobases, thymine and adenine, have been
      covalently linked at the N- and C-termini, respectively, of two alpha
      aminoisobutyric acid-rich helical peptide foldamers, aiming at driving self
      assembly through complementary recognition. A crystal-state analysis (by X-ray
      diffraction) on the shorter, achiral foldamer 1 unambiguously shows that
      adeninethymine base pairing, through Watson-Crick intermolecular H-bonding, does
      take place between either end of each peptide molecule. In the crystals, pi
      stacking between base pairs is also observed. Evidence for time-dependent
      foldameroldamer associations for the longer, chiral foldamer 2 in solution is
      provided by circular dichroism measurements. The self-assembly of foldamer 2,
      through living supramolecular polymerization, eventually leads to the formation
      of twisted fibers. Such a supramolecular organization can be affected by addition
      of either pristine adenine or thymine, that acts as a "terminator" by selectively
      matching a pairing nucleobase at one end of the foldamer. The co-assembly of
      foldamer 2 with a porphyrin-derivatized thymine, under appropriate experimental
      conditions, leads to the formation of vesicles which, in turn, can be converted
      to the fiber morphology by changing the environmental polarity. Conversely,
      dendrimeric, star polymer-like microstructures are generated when the
      supramolecular assembly of foldamer 2 is seeded by adenine-capped gold
      nanoparticles.

PMID- 28509928
TI  - Highly stable nanostructured membrane electrode assembly based on Pt/Nb2O5
      nanobelts with reduced platinum loading for proton exchange membrane fuel cells.
AB  - Proton exchange membrane fuel cells are promising candidates for the next
      generation power sources; however, poor durability and high cost impede their
      widespread application. To address this dilemma, a nanostructured membrane
      electrode assembly (MEA) based on Pt/Nb2O5 nanobelts (NBs) was constructed
      through hydrothermal synthesis and the physical vapour deposition method.
      Pt/Nb2O5 NBs were directly aligned with Nafion membrane without ionomer as a
      binder. The prepared catalyst layer is ultrathin and has ultralow Pt loading. A
      single cell performance of 5.80 kW gPt-1 (cathode) and 12.03 kW gPt-1 (anode) was
      achieved by the Pt/Nb2O5 NBs-based MEA (66.0 MUgPt cm-2). The accelerated
      durability test indicates that the Pt/Nb2O5 NBs-based MEA is far more stable than
      conventional Pt/C-based MEA.

PMID- 28509929
TI  - Borinic acid-catalyzed stereo- and site-selective synthesis of beta
      glycosylceramides.
AB  - A method for activation of unprotected ceramides towards stereo- and site
      selective glycosylation is described. Two-point binding of a diarylborinic acid
      catalyst to the ceramide accelerates its reactions with 'armed' glycosyl
      methanesulfonate donors, resulting in the formation of a beta-glycosidic linkage
      at the primary OH group.

PMID- 28509930
TI  - Elucidation of inhibitor-binding pockets of d-amino acid oxidase using docking
      simulation and N-sulfanylethylanilide-based labeling technology.
AB  - Because of the relevance of d-serine (d-Ser) to schizophrenia, inhibitors of d
      amino acid oxidase (DAO), which catalyzes degradation of d-Ser in the presence of
      flavin adenine dinucleotide (FAD), are expected to be anti-schizophrenia
      therapeutics. In this study, binding pockets of DAO to its inhibitor 4-bromo-3
      nitrobenzoic acid were searched by combining in silico docking simulation and
      labeling experiments employing an N-sulfanylethylanilide-based labeling
      technology that we have developed. The results clearly demonstrated that there
      are two binding pockets: one is shared with d-Ser and FAD, and the other is an
      unexpected cleft between the subunits of a DAO dimer. These findings will provide
      insight to aid the development of new DAO inhibitors. In addition, it was also
      proved that our labeling technology could be applicable to elucidate the binding
      pockets of proteins.

PMID- 28509932
TI  - Synthesis and activation potential of an open shell diphosphine.
AB  - A paramagnetic WIII alkyne complex bearing free terminal diphenylphosphino groups
      at the side-on coordinated alkyne was synthesized using a stepwise template
      strategy. This moderately stable metal supported open shell diphosphine shows an
      unprecedented spontaneous splitting of nitric oxide providing a WII-eta2
      C2{P(NH2)Ph2}{P(O)Ph2}+ complex featuring an amino phosphonium and a phosphine
      oxide substituent.

PMID- 28509933
TI  - Combined use of AFM and soft X-ray microscopy to reveal fibres' internalization
      in mesothelial cells.
AB  - Nanotoxicology and nanomedicine investigations often require the probing of nano
      objects such as fibres and particles in biological samples and cells, whilst
      internalization and intracellular destiny are the main issues for in vitro
      cellular studies. Various high resolution microscopy techniques are well suited
      for providing this highly sought-after information. However, sample preparation,
      nanomaterial composition and sectioning challenges make it often difficult to
      establish whether the fibres or particles have been internalized or they are
      simply overlaying or underlying the biological matter. In this paper we suggest a
      novel suitable combination of two different microscopic techniques to reveal in
      intact cells the uptake of asbestos fibres by mesothelial cells. After exposure
      to asbestos fibres and fixation, cells were first analysed under the AFM
      instrument and then imaged under the TwinMic soft X-ray microscope at Elettra
      Sincrotrone. The suggested approach combines standard soft X-ray microscopy
      imaging and AFM microscopy, with a common non-invasive sample preparation
      protocol which drastically reduces the experimental uncertainty and provides a
      quick and definitive answer to the nanoparticle cellular and tissue uptake.

PMID- 28509935
TI  - Utilization of Bone Wax as a Marker for Spatial Orientation in Intraoperative
      Magnetic Resonance Imaging.

PMID- 28509934
TI  - The role of the prefrontal cortex in freezing of gait in Parkinson's disease:
      insights from a deep repetitive transcranial magnetic stimulation exploratory
      study.
AB  - Freezing of Gait (FOG) is one of the most debilitating gait impairments in
      Parkinson's disease (PD), leading to increased fall risk and reduced health
      related quality of life. The utility of parkinsonian medications is often limited
      in the case of FOG and it frequently becomes dopamine resistant. Recent studies
      have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG;
      however, most previous findings provide only indirect evidence. To better
      understand the role of the PFC, we aimed to investigate the impact of high
      frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the
      medial PFC on FOG and its mediators. Nine patients with advanced PD participated
      in a randomized, cross-over exploratory study. We applied drTMS over the medial
      PFC for 16 weeks, with real and sham conditions; each condition included an
      intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase.
      Scores on a FOG-provoking test, the motor part of the Unified Parkinson's Disease
      Rating Scale, and gait variability significantly improved after real drTMS, but
      not after the sham condition. Self-report of FOG severity and cognitive scores
      did not improve. Due to discomfort and pain during treatment, two patients
      dropped out and the study was halted. These initial findings support the cause
      and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to
      the small sample size, findings should be interpreted cautiously. Further studies
      are needed to more fully assess the role of the medial PFC in the underlying
      mechanism of FOG and the possibility of using non-invasive brain stimulation to
      modify FOG.

PMID- 28509936
TI  - Penetrating Osseous Spicules Causing High-Flow Ventral CSF Leaks in the Setting
      of Relatively Low BMI : A Preliminary Study.
AB  - OBJECTIVE/BACKGROUND: We have anecdotally observed patients with high-flow
      ventral cerebrospinal fluid (CSF) leaks resulting from penetrating osseous
      spicules or calcified discs to be relatively thin. The purpose of this study was
      to explore the validity of this observation and determine if a potential
      association exists between low body mass index (BMI) and high-flow spinal ventral
      CSF leaks resulting from such dura-penetrating lesions. METHODS: Sixteen
      consecutive patients with precisely localized high-flow ventral spinal CSF leaks
      on dynamic myelography were identified. The cause of the CSF leak was determined.
      The BMI on the date nearest to and within 2 weeks of myelography was recorded.
      Utilizing exact sign test, the body mass index was compared to the average BMI
      from the National Health and Nutrition Examination Survey (Centers for Disease
      Control), matched to sex and age-range. RESULTS: The cohort consisted of 10 males
      (63%) and 6 females with a mean age of 54 years (range 37-72 years). In all
      patients, a spiculated osteophyte/calcified disc was identified at the site of
      the leak. Fourteen patients (88%) had a BMI below the matched national average,
      while only two patients (13%) had values above the national average (p = 0.004).
      CONCLUSIONS: Patients with high-flow ventral CSF leaks resulting from spiculated
      osteophyte or calcified disc as identified by dynamic myelography are more likely
      to have a BMI below the U.S. national average, matched for gender and age-range.
      This exploratory analysis requires confirmation as well as further
      characterization of potential pathophysiologic mechanisms and impact on
      radiographic and clinical assessments.

PMID- 28509937
TI  - Next generation sequencing is informing phenotype: a TP53 example.
AB  - The increased availability of next generation sequencing (NGS) and multi gene
      panel testing has resulted in more frequent TP53 testing of families that do not
      meet classic testing criteria. We investigated testing criteria, family history
      and result outcome in a cohort of Irish probands undergoing TP53 full sequencing.
      All TP53 test requests processed through the national genetic testing laboratory
      between 2012 and 2014 were retrospectively reviewed. Personal and family cancer
      histories were collected, including tumour type and age at diagnosis, from two
      adult cancer genetic services in Ireland. Association between Li Fraumeni
      syndrome (LFS) or Li Fraumeni like syndrome (LFL) criteria and test result was
      examined. One hundred and 35 TP53 test requests were identified. Family history
      data and test results were available on 123 of the TP53 test requests (118
      female; 5 male). 59/123 (48%) did not meet classic LFS or LFL criteria. Two
      individuals from this group harboured pathogenic TP53 mutations, giving a 3%
      mutation detection rate in those not meeting testing criteria. Both were female
      and had a personal history of early onset bilateral breast cancer with no
      reported LFS cancers in the family. 64/123 (52%) met LFS or LFL criteria and were
      all TP53 negative. 37/64 (57.8%) met Chompret criteria, 19/64 (29.7%) met Eeles
      and 7/64 (10.9%) met Eeles and Chompret and 1/64 (1.6%) met Classic LFS criteria.
      Stringent testing criteria miss germline mutations in TP53. Broadening the
      criteria for TP53 testing may improve our understanding of the phenotype and
      penetrance in the association syndrome.

PMID- 28509938
TI  - [Urethral (indwelling or intermittent) or suprapubic routes for short-term
      catheterisation in hospitalized adults].

PMID- 28509939
TI  - Bioremoval of lead using Pennisetum purpureum augmented with Enterobacter cloacae
      VITPASJ1: A pot culture approach.
AB  - Lead is a toxic heavy metal discharged into the ecosystem from various
      industries. Biological remediation strategies have been effective in the
      bioremoval of lead. In our current study, a phytobacterial system using
      Pennisetum purpureum along with lead-resistant bacterium (LRB) was employed for
      the uptake of lead. The LRB was obtained from lead-contaminated sites. The
      isolate VITPASJ1 was found to be highly tolerant to lead and was identified as an
      effective plant growth-promoting bacterium. The 16S rRNA sequencing revealed
      VITPASJ1 to be the closest neighbour of Enterobacter cloacae. The lead-resistant
      gene pbrA in the plant and the bacterium were amplified using a specific primer.
      The uptake of lead was studied by phytoremediation and rhizoremediation set-ups
      where the soil was supplemented with various concentrations of lead (50, 100, 150
      mg/kg). The plants were uprooted at regular intervals, and the translocation of
      lead into the plant was determined by atomic absorption spectroscopy. The root
      length, shoot height and chlorophyll content were found to be higher in the
      rhizoremediation set-up when compared to the phytoremediation set-up. The
      scanning electron microscopic micrographs gave a clear picture of increased
      tissue damage in the root and shoot of the phytoremediation set-up as compared to
      the rhizoremediation set-up with LRB.

PMID- 28509940
TI  - Medico-legal assessment of methamphetamine and amphetamine serum concentrations
      what can we learn from survived intoxications?
AB  - Medico-legal experts are increasingly enlisted to assess the methamphetamine and
      amphetamine serum concentrations after a criminal offense. However, since
      criminal users rarely provide useful information to medico-legal experts
      regarding the substances abused, when the substance(s) was/were used, dose of
      ingestion tools are needed to interpret the analytical data, which can be used as
      objective evidence in such cases. A comparative series of methamphetamine and
      amphetamine serum concentrations were used to analyze the frequency of
      concentrations, to determine methamphetamine/amphetamine concentration ratios,
      and prove them as a tool to distinguish pure methamphetamine from mixed
      amphetamine/methamphetamine ingestion. Additionally, two cases of survived
      accidental methamphetamine intoxication, resulting from ingestion smuggling which
      was longitudinally monitored, and pharmacokinetic parameters were assessed. In a
      series of 628 samples where the most frequent concentration of methamphetamine
      exceeded the therapeutic level, there was a strong correlation suggesting pure
      methamphetamine consumption, when the ratios of methamphetamine/amphetamine
      concentrations were within the range between 3 and 10. In the two cases of
      methamphetamine bodypacking, the relevant serum concentrations of methamphetamine
      and amphetamine, which could be measured up to 9 days after ingestion, indicated
      a decrease of the methamphetamine/amphetamine ratios in an exponential manner.
      However, the ratios were not always within the range between 3 and 10. Lastly,
      the course of the serum concentrations suggested an increase of the apparent
      elimination half-life of methamphetamine. In terms of the objective evidence
      required in criminal law, calculating methamphetamine/amphetamine concentration
      ratio is not a suitable to means to distinguish pure methamphetamine intake and
      that of mixed amphetamine/methamphetamine abuse in an individual case. Instead,
      methamphetamine high serum concentrations and the possible increase in apparent
      elimination half-life suggest that an extended detection period may be used to
      distinguish between "illicit use" as compared to "therapeutic use" of
      methamphetamine.

PMID- 28509941
TI  - Effects of perceived job insecurity on depression, suicide ideation, and decline
      in self-rated health in Korea: a population-based panel study.
AB  - PURPOSE: To investigate the effects of job security on new development of
      depressive episode, suicide ideation, and decline in self-rated health. METHODS:
      Data from the Korea Welfare Panel Study from 2012 to 2015 were analysed. A total
      of 2912 waged workers self-assessed their depressive episode, suicide ideation,
      and health annually by answering the questionnaire. Participants were divided
      into three groups according to the level of job security: high, intermediate and
      low. To evaluate the influence of job security, we performed survival analysis
      after stratification by gender with adjustment for covariates. The result was
      further stratified by whether the respondent was the head of household. RESULTS:
      After adjusting for covariates, men in low job security group showed
      significantly higher hazard ratios (HRs) for depression (HR 1.27, 95% CI 1.01
      1.60), suicide ideation (HR 3.25, 95% CI 1.72-6.16), and decline in self-rated
      health (HR 1.73, 95% CI 1.16-2.59). Women showed significantly higher HR of
      depression in the intermediate (HR 1.37, 95% CI 1.01-1.87) and low (HR 1.50, 95%
      CI 1.12-1.99) job security group. Male head of household with low job security
      showed significantly higher HR of depression, suicide ideation, and decline in
      self-rated health. Non-head-of-household women with intermediate and low job
      security showed higher risk of depression than those with high job security.
      CONCLUSIONS: We found that perceived job insecurity is associated with the new
      development of depressive episode, suicide ideation, and decline in self-rated
      health.

PMID- 28509942
TI  - Biomolecular information gained through in vitro evolution.
AB  - An in vitro evolution is a simplified Darwinian evolution in well-controlled
      surroundings. This evolution process can be modeled as a hill-climbing or
      adaptive walk on a fitness landscape in sequence space. The evolving molecular
      system gains at least two kinds of information originating from the converged
      sequences and the fitness increment of the evolving biopolymer as the adaptive
      walker. These two represent two aspects of the biomolecular information, its
      extent and its content, respectively. Here, we review studies related to
      formulation of the "content" and "extent" of biomolecular information. The two
      aspects are interconnected through physicochemical properties of the biopolymer,
      contrary to the case of conventional information, which seems to be independent
      of matter. The interconnection was analyzed based on the analogy between the
      evolution process and thermodynamics. The linear combination of the two by a
      temperature-like fluctuation factor resulted in a free-energy-like monotonically
      increasing function during the evolution process.

PMID- 28509943
TI  - New factors contributing to dynamic calcium regulation in the skeletal muscle
      triad-a crowded place.
AB  - Skeletal muscle is a highly organized tissue that has to be optimized for fast
      signalling events conveying electrical excitation to contractile response. The
      site of electro-chemico-mechanical coupling is the skeletal muscle triad where
      two membrane systems, the extracellular t-tubules and the intracellular
      sarcoplasmic reticulum, come into very close contact. Structure fits function
      here and the signalling proteins DHPR and RyR1 were the first to be discovered to
      bridge this gap in a conformational coupling arrangement. Since then, however,
      new proteins and more signalling cascades have been identified just in the last
      decade, adding more diversity and fine tuning to the regulation of excitation
      contraction coupling (ECC) and control over Ca2+ store content. The concept of
      Ca2+ entry into working skeletal muscle has become attractive again with the
      experimental evidence summarized in this review. Store-operated Ca2+ entry
      (SOCE), excitation-coupled Ca2+ entry (ECCE), action-potential-activated Ca2+
      current (APACC), and retrograde EC-coupling (ECC) are new concepts additional to
      the conventional orthograde ECC; they have provided fascinating new insights into
      muscle physiology. In this review, we discuss the discovery of these pathways,
      their potential roles, and the signalling proteins involved that show that the
      triad may become a crowded place in time.

PMID- 28509945
TI  - Ant-mediated indirect negative effects of aphids on spider mites living on the
      same plant.
AB  - Some aphid species are known to have mutualistic relationships with tending ants;
      that is, the aphids supply the ants with honeydew and are protected by the ants.
      Although spider mites and honeydew-producing aphids often live on the same host
      plant, it has not previously been determined whether the ants tending these
      aphids affect spider mite survival. Using replicated microcosms, each containing
      an artificial ant nest, we compared experimentally the survival of two-spotted
      spider mites on kidney bean plants with and without cowpea aphids. Our results
      showed significantly fewer spider mites on plants with aphids, indicating that
      spider mites were preyed upon by ants tending aphids. On the other hand, there
      was no detectable plant-mediated indirect effect of aphids on mite performance in
      the microcosms. Therefore, we conclude that aphids indirectly reduced the
      survival of spider mites living on the same host plant via their tending ants.
      Nonetheless, spider mites did not avoid settling on plant leaves infested with
      aphids.

PMID- 28509944
TI  - The physics of flagellar motion of E. coli during chemotaxis.
AB  - Flagellar motion has been an active area of study right from the discovery of
      bacterial chemotaxis in 1882. During chemotaxis, E. coli moves with the help of
      helical flagella in an aquatic environment. Helical flagella are rotated in
      clockwise or counterclockwise direction using reversible flagellar motors
      situated at the base of each flagellum. The swimming of E. coli is characterized
      by a low Reynolds number that is unique and time reversible. The random motion of
      E. coli is influenced by the viscosity of the fluid and the Brownian motion of
      molecules of fluid, chemoattractants, and chemorepellants. This paper reviews the
      literature about the physics involved in the propulsion mechanism of E. coli.
      Starting from the resistive-force theory, various theories on flagellar
      hydrodynamics are critically reviewed. Expressions for drag force, elastic force
      and velocity of flagellar elements are derived. By taking the elastic nature of
      flagella into account, linear and nonlinear equations of motions are derived and
      their solutions are presented.

PMID- 28509946
TI  - The multi-morbid old brain.

PMID- 28509947
TI  - [Arboviruses also have an American dream].
AB  - Some arboviruses that originated in the Old World have been introduced by humans
      into the American continent. The first of them was the yellow fever virus, coming
      from the West African coast with slaves in the 17th-19th centuries, followed by
      dengue viruses, which were always prevalent within the Americas. Next was theWest
      Nile virus, introduced in New York in 1999, that spread in only a few years over
      the whole continent. Then, Chikungunya virus arrived on Saint Martin Island in
      2013 after its outbreak in Polynesia; it is now widespread in the Caribbean
      Islands and on the American continent from the United States to Brazil. Finally,
      Zika virus, already active in Asia and in the South Pacific region, was
      introduced in Brazil and spread between the southern part of United States and
      south Brazil. These unexpected emergences are the consequence of the
      generalization of transoceanic trading; so, it is humans who are truly
      responsible for such transportation of viruses from the African and Asian
      continents. The mechanisms of virus establishment in unusual ecosystems have to
      be analyzed in order to understand the conditions for the circulation of the
      viruses, which supposes an adaptation to new hosts and vectors that are sometimes
      local species (like Culex vectors of West Nile virus) but mainly previously
      introduced mosquitoes (like Aedes aegypti and/or Aedes albopictus). Over time,
      all these vectors developed a strong anthropophily and, most of them, a
      remarkable adaptation to urban environment; hence, these arboviruses can
      disseminate both in rural and urban context. This type of arboviral emergences
      will certainly continue in the following years and we must imperatively develop
      preventive strategies by detecting virus mutations with capacity for emergence,
      enhancing the sensibility and rapidity of epidemiological surveillance, and
      becoming ready to face such events that cause a truly international health
      crisis.

PMID- 28509950
TI  - [Erratum to: Posterior cruciate ligament injuries].

PMID- 28509948
TI  - Discussion on "A randomized clinical trial of ultrasound-guided infra-clavicular
      cannulation of the subclavian vein in cardiac surgical patients: short-axis
      versus long-axis approach".

PMID- 28509949
TI  - Palliative care in the ICU of 2050: past is prologue.

PMID- 28509951
TI  - Costs and benefits of omnivore-mediated plant protection: effects of plant
      feeding on Salix growth more detrimental than expected.
AB  - Predators can decrease herbivore damage to plants, and this is often assumed to
      be beneficial to plant growth/reproduction without actual quantification.
      Moreover, previous studies have been biased towards strict carnivores and
      neglected the role of omnivorous predators in prey-suppression. Here, we examined
      the costs (reduction in growth) and benefits (increase in growth) of enemy
      mediated plant protection via the omnivorous (prey and plant-feeding) Orthotylus
      marginalis, relative to herbivory by a detrimental insect pest of Salix spp.
      plantations, the beetle Phratora vulgatissima. In a first experiment, we compared
      the cost of adult beetle versus omnivore nymph plant-feeding, and assessed the
      (non-) additive effects of the two types of damage. In a second experiment, we
      quantified the reduction in plant damage resulting from beetle-egg feeding by
      omnivorous nymphs and subsequent benefits to plants. We found that plant-feeding
      by omnivores negatively affected plant growth and this effect was similar to the
      cost imposed by beetle herbivory. Furthermore, simultaneous damage effects were
      additive and more detrimental than individual effects. While egg-predation by
      omnivore nymphs completely prevented beetle damage to plants, there was no
      difference in plant growth relative to only herbivore-damaged plants and growth
      was still reduced compared to control plants. Thus, despite herbivore
      suppression, there was no benefit to plant growth of omnivore-mediated plant
      protection and the negative effects of omnivore plant-feeding remained. These
      results are a first for an omnivorous enemy, and provide novel and timely
      insights on the underlying assumptions of tri-trophic associations and their use
      for biocontrol of insect pests.

PMID- 28509952
TI  - High-yield production of mannitol by Leuconostoc pseudomesenteroides CTCC G123
      from chicory-derived inulin hydrolysate.
AB  - Chicory is an agricultural plant with considerable potential as a carbohydrate
      substrate for low-cost production of biochemicals. In this work, the production
      of mannitol by Leuconostoc pseudomesenteroides CTCC G123 from chicory-derived
      inulin hydrolysate was investigated. The bioconversion process initially suffered
      from the leakage of fructose to the phosphoketolase pathway, resulting in a low
      mannitol yield. When inulin hydrolysate was supplemented with glucose as a
      substrate for mannitol production in combination with aeration induction and
      nicotinic acid induced redox modulation strategies, the mannitol yield greatly
      improved. Under these conditions, significant improvement in the glucose
      consumption rate, intracellular NADH levels and mannitol dehydrogenase specific
      activity were observed, with mannitol production increasing from 64.6 to 88.1 g/L
      and overall yield increase from 0.69 to 0.94 g/g. This work demonstrated an
      efficient method for the production of mannitol from inulin hydrolysate with a
      high overall yield.

PMID- 28509953
TI  - Hyalinizing Clear Cell Carcinoma of the Tonsil: A Case Report.
AB  - Hyalinzing clear cell carcinoma is a rare tumor of the oral cavity and is even
      more rarely located in the tonsil. Here, we present a case report of a
      pedunculated tonsillar mass in a nearly asymptomatic patient that was present for
      2 years prior to removal. Complete surgical excision was achieved and no adjuvant
      therapy was recommended. We include a discussion of this rare pathology and its
      typical clinical presentation and course.

PMID- 28509954
TI  - Evidence in the human of a hypotensive and a bradycardic effect after mouth
      opening maintained for 10 min.
AB  - PURPOSE: We have recently shown that in humans submaximal mouth opening
      associated with partial masticatory movements for 10 min is followed by a small
      but significant and prolonged reduction of blood pressure and heart rate. We here
      report the effects of a fixed mouth opener. METHODS: In 22 seated normotensive
      volunteers the effect on blood pressure and heart rate was studied in randomized
      order after fixed mandibular extension and after a control procedure consisting
      in keeping a stick between the incisor teeth (both for 10 min). Automated
      recordings every 10 min were done for 40 min before and 120 min following the
      procedure. RESULTS: Two-way ANOVA for repeated measures on absolute values
      (actual recordings) and on changes from baseline revealed that, compared to
      controls, systolic, diastolic and mean blood pressure and heart rate were
      significantly lower after mandibular extension. Compared to controls, mandibular
      extension induced an average blood pressure drop of 2.88 mmHg (systolic), 2.55
      mmHg (diastolic) and 2.42 mmHg (mean) over the entire observation period. The
      average decline over the central part of the observation period (30th to 80th
      min) was, respectively, of 3.62, 3.70 and 3.61 mmHg. The decrements of heart rate
      were of 2.11 and 2.66 beats per min. All these differences were statistically
      significant. The hypotensive and bradycardic responses persisted for 70-120 min.
      CONCLUSIONS: This study shows that, in normotensives, a single fixed submaximal
      mouth opening for 10 min is followed by prolonged albeit small reductions of
      blood pressure and heart rate.

PMID- 28509955
TI  - Volunteers' Experiences Delivering a Community-University Chronic Disease Health
      Awareness Program for South Asian Older Adults.
AB  - Volunteers and voluntary organizations can connect preventative health care
      programs to communities and may play an important role in addressing the health
      needs of older adults. Despite this, tensions may exist in the structures that
      drive volunteers and voluntary organizations representing immigrant communities
      to provide unpaid labour to augment and supplement health care services.
      Furthermore, organizational challenges may exist for community agencies relying
      on volunteers to sustain a health screening and education program. The
      intervention program was led by one voluntary agency specifically for South Asian
      communities in partnership with the university and five local organizations. This
      paper draws on volunteer surveys (n = 22) and key informant interviews (n = 12)
      to detail volunteer experiences providing this intervention. Volunteers were
      university students and other community volunteers. A total of 810 adults
      participated in the intervention within the Greater Toronto Area, Ontario, Canada
      between October 2014 and June 2016. We found that volunteers often used their
      experience as a 'stepping stone' position to other education or work. They also
      gained from the knowledge and used it to educate themselves and their family
      members and friends. This paper provides a critical reflection on the role of
      volunteers in a preventative and educational healthcare intervention program for
      older adults from the South Asian community. Tensions exist when relying on
      volunteer labour for the implementation of preventative community health care
      programming and must be explored to ensure program sustainability as well as
      equity within the health care system.

PMID- 28509956
TI  - Classical protein kinases C are regulated by concerted interaction with lipids:
      the importance of phosphatidylinositol-4,5-bisphosphate.
AB  - Classical protein kinase C (PKC) enzymes are known to be important factors in
      cell physiology both in terms of health and disease. They are activated by
      triggering signals that induce their translocation to membranes. The consensus
      view is that several secondary messengers are involved in this activation, such
      as cytosolic Ca2+ and diacylglycerol. Cytosolic Ca2+ bridges the C2 domain to
      anionic phospholipids as phosphatidylserine in the membrane, and diacylglycerol
      binds to the C1 domain. Both diacylglycerol and the increase in Ca2+
      concentration are assumed to arise from the extracellular signal that triggers
      the hydrolysis of phosphatidylinositol-4,5-bisphosphate. However, results
      obtained during the last decade indicate that this phosphoinositide itself is
      also responsible for modulating classical PKC activity and its localization in
      the plasma membrane.

PMID- 28509957
TI  - Calcium channels and synaptic transmission in familial hemiplegic migraine type 1
      animal models.
AB  - One of the outstanding developments in clinical neurology has been the
      identification of ion channel mutations as the origin of a wide variety of
      inherited disorders like migraine, epilepsy, and ataxia. The study of several
      channelopathies has provided crucial insights into the molecular mechanisms,
      pathogenesis, and therapeutic approaches to complex neurological diseases. This
      review addresses the mutations underlying familial hemiplegic migraine (FHM) with
      particular interest in Cav2.1 (i.e., P/Q-type) voltage-activated Ca2+ channel FHM
      type-1 mutations (FHM1). Transgenic mice harboring the human pathogenic FHM1
      mutation R192Q or S218L (KI) have been used as models to study neurotransmission
      at several central and peripheral synapses. FHM1 KI mice are a powerful tool to
      explore presynaptic regulation associated with expression of Cav2.1 channels.
      FHM1 Cav2.1 channels activate at more hyperpolarizing potentials and show an
      increased open probability. These biophysical alterations may lead to a gain-of
      function on synaptic transmission depending upon factors such as action potential
      waveform and/or Cav2.1 splice variants and auxiliary subunits. Analysis of FHM
      knock-in mouse models has demonstrated a deficient regulation of the cortical
      excitation/inhibition (E/I) balance. The resulting excessive increases in
      cortical excitation may be the mechanisms that underlie abnormal sensory
      processing together with an increase in the susceptibility to cortical spreading
      depression (CSD). Increasing evidence from FHM KI animal studies support the idea
      that CSD, the underlying mechanism of aura, can activate trigeminal nociception,
      and thus trigger the headache mechanisms.

PMID- 28509959
TI  - Membrane changes under oxidative stress: the impact of oxidized lipids.
AB  - Studying photosensitized oxidation of unsaturated phospholipids is of importance
      for understanding the basic processes underlying photodynamic therapy, photoaging
      and many other biological dysfunctions. In this review we show that the giant
      unilamellar vesicle, when used as a simplified model of biological membranes, is
      a powerful tool to investigate how in situ photogenerated oxidative species
      impact the phospholipid bilayer. The extent of membrane damage can be modulated
      by choosing a specific photosensitizer (PS) which is activated by light
      irradiation and can react by either type I and or type II mechanism. We will show
      that type II PS generates only singlet oxygen which reacts to the phospholipid
      acyl double bond. The byproduct thus formed is a lipid hydroperoxide which
      accumulates in the membrane as a function of singlet oxygen production and
      induces an increase in its area without significantly affecting membrane
      permeability. The presence of a lipid hydroperoxide can also play an important
      role in the formation of the lipid domain for mimetic plasma membranes. Lipid
      hydroperoxides can be also transformed in shortened chain compounds, such as
      aldehydes and carboxylic acids, in the presence of a PS that reacts via the type
      I mechanism. The presence of such byproducts may form hydrophilic pores in the
      membrane for moderate oxidative stress or promote membrane disruption for massive
      oxidation. Our results provide a new tool to explore membrane response to an
      oxidative stress and may have implications in biological signaling of redox
      misbalance.

PMID- 28509958
TI  - Receptor-ligand molecular docking.
AB  - Docking methodology aims to predict the experimental binding modes and affinities
      of small molecules within the binding site of particular receptor targets and is
      currently used as a standard computational tool in drug design for lead compound
      optimisation and in virtual screening studies to find novel biologically active
      molecules. The basic tools of a docking methodology include a search algorithm
      and an energy scoring function for generating and evaluating ligand poses. In
      this review, we present the search algorithms and scoring functions most commonly
      used in current molecular docking methods that focus on protein-ligand
      applications. We summarise the main topics and recent computational and
      methodological advances in protein-ligand docking. Protein flexibility, multiple
      ligand binding modes and the free-energy landscape profile for binding affinity
      prediction are important and interconnected challenges to be overcome by further
      methodological developments in the docking field.

PMID- 28509960
TI  - Pathological implications of nucleic acid interactions with proteins associated
      with neurodegenerative diseases.
AB  - Protein misfolding disorders (PMDs) refer to a group of diseases related to the
      misfolding of particular proteins that aggregate and deposit in the cells and
      tissues of humans and other mammals. The mechanisms that trigger protein
      misfolding and aggregation are still not fully understood. Increasing
      experimental evidence indicates that abnormal interactions between PMD-related
      proteins and nucleic acids (NAs) can induce conformational changes. Here, we
      discuss these protein-NA interactions and address the role of deoxyribonucleic
      (DNA) and ribonucleic (RNA) acid molecules in the conformational conversion of
      different proteins that aggregate in PMDs, such as Alzheimer's, Parkinson's, and
      prion diseases. Studies on the affinity, stability, and specificity of proteins
      involved in neurodegenerative diseases and NAs are specifically addressed. A
      landscape of reciprocal effects resulting from the binding of prion proteins,
      amyloid-beta peptides, tau proteins, huntingtin, and alpha-synuclein are
      presented here to clarify the possible role of NAs, not only as encoders of
      genetic information but also in triggering PMDs.

PMID- 28509961
TI  - IL-4: an important cytokine in determining the fate of T cells.
AB  - The pleiotropic effect of cytokines has been well documented, but the effects
      triggered by unique cytokines in different T cell types are still under
      investigation. The most relevant findings on the influence of interleukin-4 (IL
      4) on T cell activation, differentiation, proliferation, and survival of
      different T cell types are discussed in this review. The main aim of our study
      was to correlate the observed effect with the corresponding molecular mechanism
      induced on IL-4/IL-4R interaction, in an effort to understand how the same
      extracellular stimuli can trigger a wide spectrum of signaling pathways leading
      to different responses in each T cell type.

PMID- 28509963
TI  - Electric dipole moments of the fluorescent probes Prodan and Laurdan:
      experimental and theoretical evaluations.
AB  - Several experimental and theoretical approaches can be used for a comprehensive
      understanding of solvent effects on the electronic structure of solutes. In this
      review, we revisit the influence of solvents on the electronic structure of the
      fluorescent probes Prodan and Laurdan, focusing on their electric dipole moments.
      These biologically used probes were synthesized to be sensitive to the
      environment polarity. However, their solvent-dependent electronic structures are
      still a matter of discussion in the literature. The absorption and emission
      spectra of Prodan and Laurdan in different solvents indicate that the two probes
      have very similar electronic structures in both the ground and excited states.
      Theoretical calculations confirm that their electronic ground states are very
      much alike. In this review, we discuss the electric dipole moments of the ground
      and excited states calculated using the widely applied Lippert-Mataga equation,
      using both spherical and spheroid prolate cavities for the solute. The dimensions
      of the cavity were found to be crucial for the calculated dipole moments. These
      values are compared to those obtained by quantum mechanics calculations,
      considering Prodan in vacuum, in a polarizable continuum solvent, and using a
      hybrid quantum mechanics-molecular mechanics methodology. Based on the
      theoretical approaches it is evident that the Prodan dipole moment can change
      even in the absence of solute-solvent-specific interactions, which is not taken
      into consideration with the experimental Lippert-Mataga method. Moreover, in
      water, for electric dipole moment calculations, it is fundamental to consider
      hydrogen-bonded molecules.

PMID- 28509962
TI  - Thiol redox biochemistry: insights from computer simulations.
AB  - Thiol redox chemical reactions play a key role in a variety of physiological
      processes, mainly due to the presence of low-molecular-weight thiols and cysteine
      residues in proteins involved in catalysis and regulation. Specifically, the
      subtle sensitivity of thiol reactivity to the environment makes the use of
      simulation techniques extremely valuable for obtaining microscopic insights. In
      this work we review the application of classical and quantum-mechanical atomistic
      simulation tools to the investigation of selected relevant issues in thiol redox
      biochemistry, such as investigations on (1) the protonation state of cysteine in
      protein, (2) two-electron oxidation of thiols by hydroperoxides, chloramines, and
      hypochlorous acid, (3) mechanistic and kinetics aspects of the de novo formation
      of disulfide bonds and thiol-disulfide exchange, (4) formation of sulfenamides,
      (5) formation of nitrosothiols and transnitrosation reactions, and (6) one
      electron oxidation pathways.

PMID- 28509967
TI  - Successful Latin American initiatives in biophysics.

PMID- 28509966
TI  - Rate of solute incorporation to liposomes evaluated from encapsulated enzymes
      activities.
AB  - There are numerous studies on systems comprising an enzyme encapsulated in
      unilamellar liposomes and its substrate initially present in the external aqueous
      media. Most of these studies are focused on enzyme stability and activity in a
      restricted media. However, the rate of the process is also determined by the
      capacity of the substrate to permeate towards the liposome inner pool. In spite
      of this, there are few studies aimed at a quantitative evaluation of the
      substrate permeation rate and its lifetime inside the liposome pool. In the
      present work, we describe, in terms of a very simple mechanism, the permeation of
      glucose and hydrogen peroxide in DPPC unilamellar liposomes. To this aim, we
      evaluated the rate of the process employing encapsulated glucose oxidase and
      catalase in the kinetic diffusion controlled limit. Under this condition, the
      rate of the process becomes zero order in the enzyme and allows a direct
      evaluation of the rate constant for the permeation process and the lifetime of a
      substrate molecule incorporated into the liposome inner pool.

PMID- 28509965
TI  - Antimony transport mechanisms in resistant leishmania parasites.
AB  - Antimonial compounds have been used for more than a century in the treatment of
      the parasitic disease leishmaniasis. Although pentavalent antimonials are still
      first-line drugs in several developing countries, this class of drugs is no
      longer recommended in the Indian sub-continent because of the emergence of drug
      resistance. The precise mechanisms involved in the resistance of leishmania
      parasites to antimony are still subject to debate. It is now well documented that
      drug resistance in leishmania parasites is a multifactorial phenomenon involving
      multiple genes whose expression pattern synergistically leads to the resistance
      phenotype. The reduction of intracellular antimony accumulation is a frequent
      change observed in resistant leishmania cells; however, no comprehensive
      transport model has been presented so far to explain this change and its
      contribution to Leishmania resistance. The present review firstly covers the
      actual knowledge on the metabolism of antimonial drugs, the mechanisms of their
      transmembrane transport and intracellular processing in Leishmania. It further
      describes both the functional and molecular changes associated with Sb resistance
      in this organism. Possible transport models based on the actual knowledge are
      then presented, as well as their functional implications. Biophysical and
      pharmacological strategies are finally proposed for the precise identification of
      the transport pathways.

PMID- 28509969
TI  - Epidemiology of prostate cancer.

PMID- 28509970
TI  - Testis cancer: some problems still remain unsolved.

PMID- 28509968
TI  - Sleep problems in children with attention-deficit hyperactivity disorder:
      associations with parenting style and sleep hygiene.
AB  - We aimed to examine the association between sleep problems and parenting and
      sleep hygiene in children with attention-deficit/hyperactivity disorder (ADHD).
      Participants included 5-13-year-old children with DSM 5 defined ADHD and a parent
      reported moderate-to-severe sleep problem (N = 361). Sleep was assessed using the
      parent-reported Children's Sleep Habits Questionnaire. Parents also completed
      checklists assessing sleep hygiene, parenting consistency, and parenting warmth.
      Linear regression established prediction models controlling for confounding
      variables including child age and sex, ADHD symptom severity, comorbidities,
      medication use, and socio-demographic factors. More consistent parenting was
      associated with decreased bedtime resistance (beta = -0.16) and decreased sleep
      anxiety (beta = -0.14), while greater parental warmth was associated with
      increased parasomnias (beta = +0.18) and sleep anxiety (beta = +0.13). Poorer
      sleep hygiene was associated with increased bedtime resistance (beta = +0.20),
      increased daytime sleepiness (beta = +0.12), and increased sleep duration
      problems (beta = +0.13). In conclusion, sleep hygiene and parenting are important
      modifiable factors independently associated with sleep problems in children with
      ADHD. These factors should be considered in the management of sleep problems in
      children with ADHD.

PMID- 28509971
TI  - Description of Chryseobacterium timonianum sp. nov., isolated from a patient with
      pneumonia.
AB  - Using a polyphasic taxonomic strategy, an aerobic, Gram-negative, non-motile,
      yellow pigmented rod isolated from a sputum sample of a patient with pneumonia
      was characterised. This bacterial strain, designated G972T, could not be
      identified by our systematic MALDI-TOF screening on a MicroFlex. This led to the
      sequencing of the 16S rRNA gene, which shows 98.57% sequence identity with that
      of Chryseobacterium indologenes 16777T, the phylogenetic closely related type
      strain of a species with standing in nomenclature, which putatively classifies it
      as a new species. The major cell fatty acids were identified as 13-methyl
      tetradecanoic acid (61%), 3-hydroxy-heptadecanoic acid (16%) and 15-methyl-11
      hexadecenoic acid (11%). D-glucose, D-mannose, aesculin, D-maltose, D-trehalose,
      and gentibiose are the main carbon source. Digital DNA-DNA hybridization (dDDH)
      estimation and average nucleotide identity values (ANI) of the strain G972T
      against genomes of the type strains of related species ranged between 18.9 and
      32.8% and between 71.46 and 83.61%, respectively, thus confirming again the new
      species status of the strain. Here, we describe the characteristics of this
      organism, complete genome sequence and annotation. The 5,390,132 bp size genome
      contains 4867 protein-coding genes, 89 RNAs (three genes are 5S rRNA, one gene is
      16S rRNA, one gene is 23S rRNA and 84 tRNAs) with 35.51% GC content. Finally, on
      the basis of these polyphasic data, consisting of phenotypic and genomic
      analyses, we conclude that strain strain G972T (= DSM 103388T = CSUR P2233T)
      represents a novel species for which we propose the name Chryseobacterium
      timonianum. The 16S rRNA and genome sequences are available in GenBank database
      under accession numbers LT161886 and FJVD00000000.

PMID- 28509973
TI  - Molecular mechanisms of inherited thoracic aortic disease - from gene variant to
      surgical aneurysm.
AB  - Aortic dissection is a catastrophic event that has a high mortality rate.
      Thoracic aortic aneurysms are the clinically silent precursor that confers an
      increased risk of acute aortic dissection. There are several gene mutations that
      have been identified in key structural and regulatory proteins within the aortic
      wall that predispose to thoracic aneurysm formation. The most common and well
      characterised of these is the FBN1 gene mutation that is known to cause Marfan
      syndrome. Others less well-known mutations include TGF-beta1 and TGF-beta2
      receptor mutations that cause Loeys-Dietz syndrome, Col3A1 mutations causing
      Ehlers-Danlos Type 4 syndrome and Smad3 and-4, ACTA2 and MYHII mutations that
      cause familial thoracic aortic aneurysm and dissection. Despite the variation in
      the proteins affected by these genetic mutations, there is a unifying
      pathological end point of medial degeneration within the wall of the aorta
      characterised by vascular smooth muscle cell loss, fragmentation and loss of
      elastic fibers, and accumulation of proteoglycans and glycosaminoglycans within
      vascular smooth muscle cell-depleted areas of the aortic media. Our understanding
      of these mutations and their post-translational effects has led to a greater
      understanding of the pathophysiology that underlies thoracic aortic aneurysm
      formation. Despite this, there are still many unanswered questions regarding the
      molecular mechanisms. Further elucidation of the signalling pathways will help us
      identify targets that may be suitable modifiers to enhance treatment of this
      often fatal condition.

PMID- 28509972
TI  - Cardiac stem cells: translation to human studies.
AB  - The discovery of multiple classes of cardiac progenitor cells in the adult
      mammalian heart has generated hope for their use as a therapeutic in heart
      failure. However, successful results from animal models have not always yielded
      similar findings in human studies. Recent Phase I/II trials of c-Kit (SCIPIO) and
      cardiosphere-based (CADUCEUS) cardiac progenitor cells have demonstrated safety
      and some therapeutic efficacy. Gaps remain in our understanding of the origins,
      function and relationships between the different progenitor cell families, many
      of which are heterogeneous populations with overlapping definitions. Another
      challenge lies in the limitations of small animal models in replicating the human
      heart. Cryopreserved human cardiac tissue provides a readily available source of
      cardiac progenitor cells and may help address these questions. We review
      important findings and relative unknowns of the main classes of cardiac
      progenitor cells, highlighting differences between animal and human studies.

PMID- 28509964
TI  - The excitation-contraction coupling mechanism in skeletal muscle.
AB  - First coined by Alexander Sandow in 1952, the term excitation-contraction
      coupling (ECC) describes the rapid communication between electrical events
      occurring in the plasma membrane of skeletal muscle fibres and Ca2+ release from
      the SR, which leads to contraction. The sequence of events in twitch skeletal
      muscle involves: (1) initiation and propagation of an action potential along the
      plasma membrane, (2) spread of the potential throughout the transverse tubule
      system (T-tubule system), (3) dihydropyridine receptors (DHPR)-mediated detection
      of changes in membrane potential, (4) allosteric interaction between DHPR and
      sarcoplasmic reticulum (SR) ryanodine receptors (RyR), (5) release of Ca2+ from
      the SR and transient increase of Ca2+ concentration in the myoplasm, (6)
      activation of the myoplasmic Ca2+ buffering system and the contractile apparatus,
      followed by (7) Ca2+ disappearance from the myoplasm mediated mainly by its
      reuptake by the SR through the SR Ca2+ adenosine triphosphatase (SERCA), and
      under several conditions movement to the mitochondria and extrusion by the
      Na+/Ca2+ exchanger (NCX). In this text, we review the basics of ECC in skeletal
      muscle and the techniques used to study it. Moreover, we highlight some recent
      advances and point out gaps in knowledge on particular issues related to ECC such
      as (1) DHPR-RyR molecular interaction, (2) differences regarding fibre types, (3)
      its alteration during muscle fatigue, (4) the role of mitochondria and store
      operated Ca2+ entry in the general ECC sequence, (5) contractile potentiators,
      and (6) Ca2+ sparks.

PMID- 28509975
TI  - Adaptations of cytoarchitecture in human dilated cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is characterised by a histological phenotype of
      myocyte disarray, but heart tissue samples from patients with dilated
      cardiomyopathy (DCM) often look comparatively similar to those from healthy
      individuals apart from conspicuous regions of fibrosis and necrosis. We have
      previously investigated subcellular alterations in the cytoarchitecture of mouse
      models of dilated cardiomyopathy and found that both the organisation and
      composition of the intercalated disc, i.e. the specialised type of cell-cell
      contact in the heart, is altered. There is also is a change in the composition of
      the M-band of the sarcomere due to an expression shift towards the more
      extensible embryonic heart (EH)-myomesin isoform. Analysis of human samples from
      the Sydney Human Heart Tissue Bank have revealed similar structural findings and
      also provided evidence for a dramatic change in overall cardiomyocyte size
      control, which has also been seen in the mouse. Together these changes in
      cytoarchitecture probably contribute to the decreased functional output that is
      seen in DCM.

PMID- 28509976
TI  - Mechanisms of SR calcium release in healthy and failing human hearts.
AB  - Normal heart contraction and rhythm relies on the proper flow of calcium ions
      (Ca2+) into cardiac cells and between their intracellular organelles, and any
      disruption can lead to arrhythmia and sudden cardiac death. Electrical excitation
      of the surface membrane activates voltage-dependent L-type Ca2+ channels to open
      and allow Ca2+ to enter the cytoplasm. The subsequent increase in cytoplasmic
      Ca2+ concentration activates calcium release channels (RyR2) located at
      specialised Ca2+ release sites in the sarcoplasmic reticulum (SR), which serves
      as an intracellular Ca2+ store. Animal models have provided valuable insights
      into how intracellular Ca2+ transport mechanisms are altered in human heart
      failure. The aim of this review is to examine how Ca2+ release sites are
      remodelled in heart failure and how this affects intracellular Ca2+ transport
      with an emphasis on Ca2+ release mechanisms in the SR. Current knowledge on how
      heart failure alters the regulation of RyR2 by Ca2+ and Mg2+ and how these
      mechanisms control the activity of RyR2 in the confines of the Ca2+ release sites
      is reviewed.

PMID- 28509977
TI  - The role of super-relaxed myosin in skeletal and cardiac muscle.
AB  - The super-relaxed (SRX) state of myosin was only recently reported in striated
      muscle. It is characterised by a sub-population of myosin heads with a highly
      inhibited rate of ATP turnover. Myosin heads in the SRX state are bound to each
      other along the thick filament core producing a highly ordered arrangement. Upon
      activation, these heads project into the interfilament space where they can bind
      to the actin filaments. Thus far, the population and lifetimes of myosin heads in
      the SRX state have been characterised in rabbit cardiac, and fast and slow
      skeletal muscle, as well as in the skeletal muscle of the tarantula. These
      studies suggest that the role of SRX in cardiac and skeletal muscle regulation is
      tailored to their specific functions. In skeletal muscle, the SRX modulates the
      resting metabolic rate. Cardiac SRX represents a "reserve" of inactive myosin
      heads that may protect the heart during times of stress, e.g. hypoxia and
      ischaemia. These heads may also be called up when there is a sustained demand for
      increased power. The SRX in cardiac muscle provides a potential target for novel
      therapies.

PMID- 28509974
TI  - Decoding the complex genetic causes of heart diseases using systems biology.
AB  - The pace of disease gene discovery is still much slower than expected, even with
      the use of cost-effective DNA sequencing and genotyping technologies. It is
      increasingly clear that many inherited heart diseases have a more complex
      polygenic aetiology than previously thought. Understanding the role of gene-gene
      interactions, epigenetics, and non-coding regulatory regions is becoming
      increasingly critical in predicting the functional consequences of genetic
      mutations identified by genome-wide association studies and whole-genome or exome
      sequencing. A systems biology approach is now being widely employed to
      systematically discover genes that are involved in heart diseases in humans or
      relevant animal models through bioinformatics. The overarching premise is that
      the integration of high-quality causal gene regulatory networks (GRNs), genomics,
      epigenomics, transcriptomics and other genome-wide data will greatly accelerate
      the discovery of the complex genetic causes of congenital and complex heart
      diseases. This review summarises state-of-the-art genomic and bioinformatics
      techniques that are used in accelerating the pace of disease gene discovery in
      heart diseases. Accompanying this review, we provide an interactive web-resource
      for systems biology analysis of mammalian heart development and diseases,
      CardiacCode ( http://CardiacCode.victorchang.edu.au/ ). CardiacCode features a
      dataset of over 700 pieces of manually curated genetic or molecular perturbation
      data, which enables the inference of a cardiac-specific GRN of 280 regulatory
      relationships between 33 regulator genes and 129 target genes. We believe this
      growing resource will fill an urgent unmet need to fully realise the true
      potential of predictive and personalised genomic medicine in tackling human heart
      disease.

PMID- 28509978
TI  - Surgery for hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a genetically determined cardiac disease
      characterised by otherwise unexplained myocardial hypertrophy of the left
      ventricle, and may result in left ventricular outflow tract obstruction. It is
      the most common cause of sudden cardiac death in young adults due to arrhythmias.
      Septal myectomy is a surgical treatment for HCM with moderate to severe outflow
      tract obstruction, and is indicated for patients with severe symptoms refractory
      to medical therapy. The surgical approach involves obtaining access to the
      interventricular septum via transaortic, transapical or transmitral approaches,
      and excising a portion of the hypertrophied myocardium to relieve the outflow
      tract obstruction. Large, contemporary series from centres experienced in septal
      myectomy patients have demonstrated a low early mortality of <2 %, excellent long
      term survival that matches the general population, and durable relief of
      symptoms.

PMID- 28509979
TI  - G protein-coupled receptors in cardiac biology: old and new receptors.
AB  - G protein-coupled receptors (GPCRs) are seven-transmembrane-spanning proteins
      that mediate cellular and physiological responses. They are critical for
      cardiovascular function and are targeted for the treatment of hypertension and
      heart failure. Nevertheless, current therapies only target a small fraction of
      the cardiac GPCR repertoire, indicating that there are many opportunities to
      investigate unappreciated aspects of heart biology. Here, we offer an update on
      the contemporary view of GPCRs and the complexities of their signalling, and
      review the roles of the 'classical' GPCRs in cardiovascular physiology and
      disease. We then provide insights into other GPCRs that have been less
      extensively studied in the heart, including orphan, odorant and taste receptors.
      We contend that these novel cardiac GPCRs contribute to heart function in health
      and disease and thereby offer exciting opportunities to therapeutically modulate
      heart function.

PMID- 28509983
TI  - Special Issue on human heart failure.

PMID- 28509985
TI  - Structural and biophysical properties of the integrin-associated cytoskeletal
      protein talin.
AB  - Talin is a large cytoskeletal protein (2541 amino acid residues) which plays a
      key role in integrin-mediated events that are crucial for cell adhesion,
      migration, proliferation and survival. This review summarises recent work on the
      structure of talin and on some of the structurally better defined interactions
      with other proteins. The N-terminal talin head (approx. 50 kDa) consists of an
      atypical FERM domain linked to a long flexible rod (approx. 220 kDa) made up of a
      series of amphipathic helical bundle domains. The F3 FERM subdomain in the head
      binds the cytoplasmic tail of integrins, but this interaction can be inhibited by
      an interaction of F3 with a helical bundle in the talin rod, the so-called
      "autoinhibited form" of the molecule. The talin rod contains a second integrin
      binding site, at least two actin-binding sites and a large number of binding
      sites for vinculin, which is important in reinforcing the initial integrin-actin
      link mediated by talin. The vinculin binding sites are defined by hydrophobic
      residues buried within helical bundles, and these must unfold to allow vinculin
      binding. Recent experiments suggest that this unfolding may be mediated by
      mechanical force exerted on the talin molecule by actomyosin contraction.

PMID- 28509984
TI  - Spontaneous oscillatory contraction (SPOC) in cardiomyocytes.
AB  - SPOC (spontaneous oscillatory contraction) is a characteristic state of the
      contractile system of striated (skeletal and cardiac) muscle that exists between
      the states of relaxation and contraction. For example, Ca-SPOCs occur at
      physiological Ca2+ levels (pCa ~6.0), whereas ADP-SPOC occurs in the virtual
      absence of Ca2+ (pCa >= 8; relaxing conditions in the presence of MgATP), but in
      the presence of inorganic phosphate (Pi) and a high concentration of MgADP. The
      concentration of Mg-ADP necessary for SPOC is nearly equal to or greater than the
      MgATP concentration for cardiac muscle and is several times higher for skeletal
      muscle. Thus, the cellular conditions for SPOC are broader in cardiac muscle than
      in skeletal muscle. During these SPOCs, each sarcomere in a myofibril undergoes
      length oscillation that has a saw-tooth waveform consisting of a rapid
      lengthening and a slow shortening phase. The lengthening phase of one half of a
      sarcomere is transmitted to the adjacent half of the sarcomere successively,
      forming a propagating wave (termed a SPOC wave). The SPOC waves are synchronized
      across the cardiomyocytes resulting in a visible wave of successive contractions
      and relaxations termed the SPOC wave. Experimentally, the SPOC period (and
      therefore the velocity of SPOC wave) is observed in demembranated cardiomyocytes
      and can be prepared from a wide range of animal hearts. These periods correlate
      well with the resting heartbeats of a wide range of mammals (rat, rabbit, dog,
      pig and cow). Preliminary experiments showed that the SPOC properties of human
      cardiomyocytes are similar to the heartbeat of a large dog or a pig. This
      correlation suggests that SPOCs may play a fundamental role in the heart. Here,
      we briefly summarize a range of SPOC parameters obtained experimentally, and
      relate them to a theoretical model to explain those characteristics. Finally, we
      discuss the possible significance of these SPOC properties in each and every
      heartbeat.

PMID- 28509981
TI  - Microdomain-specific localization of functional ion channels in cardiomyocytes:
      an emerging concept of local regulation and remodelling.
AB  - Cardiac excitation involves the generation of action potential by individual
      cells and the subsequent conduction of the action potential from cell to cell
      through intercellular gap junctions. Excitation of the cellular membrane results
      in opening of the voltage-gated L-type calcium ion (Ca2+) channels, thereby
      allowing a small amount of Ca2+ to enter the cell, which in turn triggers the
      release of a much greater amount of Ca2+ from the sarcoplasmic reticulum, the
      intracellular Ca2+ store, and gives rise to the systolic Ca2+ transient and
      contraction. These processes are highly regulated by the autonomic nervous
      system, which ensures the acute and reliable contractile function of the heart
      and the short-term modulation of this function upon changes in heart rate or
      workload. It has recently become evident that discrete clusters of different ion
      channels and regulatory receptors are present in the sarcolemma, where they form
      an interacting network and work together as a part of a macro-molecular
      signalling complex which in turn allows the specificity, reliability and accuracy
      of the autonomic modulation of the excitation-contraction processes by a variety
      of neurohormonal pathways. Disruption in subcellular targeting of ion channels
      and associated signalling proteins may contribute to the pathophysiology of a
      variety of cardiac diseases, including heart failure and certain arrhythmias.
      Recent methodological advances have made it possible to routinely image the
      topography of live cardiomyocytes, allowing the study of clustering functional
      ion channels and receptors as well as their coupling within a specific
      microdomain. In this review we highlight the emerging understanding of the
      functionality of distinct subcellular microdomains in cardiac myocytes (e.g. T
      tubules, lipid rafts/caveolae, costameres and intercalated discs) and their
      functional role in the accumulation and regulation of different subcellular
      populations of sodium, Ca2+ and potassium ion channels and their contributions to
      cellular signalling and cardiac pathology.

PMID- 28509982
TI  - Phospholamban phosphorylation, mutation, and structural dynamics: a biophysical
      approach to understanding and treating cardiomyopathy.
AB  - We review the recent development of novel biochemical and spectroscopic methods
      to determine the site-specific phosphorylation, expression, mutation, and
      structural dynamics of phospholamban (PLB), in relation to its function
      (inhibition of the cardiac calcium pump, SERCA2a), with specific focus on cardiac
      physiology, pathology, and therapy. In the cardiomyocyte, SERCA2a actively
      transports Ca2+ into the sarcoplasmic reticulum (SR) during relaxation (diastole)
      to create the concentration gradient that drives the passive efflux of Ca2+
      required for cardiac contraction (systole). Unphosphorylated PLB (U-PLB) inhibits
      SERCA2a, but phosphorylation at S16 and/or T17 (producing P-PLB) changes the
      structure of PLB to relieve SERCA2a inhibition. Because insufficient SERCA2a
      activity is a hallmark of heart failure, SERCA2a activation, by gene therapy
      (Andino et al. 2008; Fish et al. 2013; Hoshijima et al. 2002; Jessup et al. 2011)
      or drug therapy (Ferrandi et al. 2013; Huang 2013; Khan et al. 2009; Rocchetti et
      al. 2008; Zhang et al. 2012), is a widely sought goal for treatment of heart
      failure. This review describes rational approaches to this goal. Novel
      biophysical assays, using site-directed labeling and high-resolution
      spectroscopy, have been developed to resolve the structural states of SERCA2a-PLB
      complexes in vitro and in living cells. Novel biochemical assays, using synthetic
      standards and multidimensional immunofluorescence, have been developed to
      quantitate PLB expression and phosphorylation states in cells and human tissues.
      The biochemical and biophysical properties of U-PLB, P-PLB, and mutant PLB will
      ultimately resolve the mechanisms of loss of inhibition and gain of inhibition to
      guide therapeutic development. These assays will be powerful tools for
      investigating human tissue samples from the Sydney Heart Bank, for the purpose of
      analyzing and diagnosing specific disorders.

PMID- 28509980
TI  - The role of TGFbeta1 and LRG1 in cardiac remodelling and heart failure.
AB  - Heart failure is a life-threatening condition that carries a considerable
      emotional and socio-economic burden. As a result of the global increase in the
      ageing population, sedentary life-style, increased prevalence of risk factors,
      and improved survival from cardiovascular events, the incidence of heart failure
      will continue to rise. Despite the advances in current cardiovascular therapies,
      many patients are not suitable for or may not benefit from conventional
      treatments. Thus, more effective therapies are required. Transforming growth
      factor (TGF) beta family of cytokines is involved in heart development and dys
      regulated TGFbeta signalling is commonly associated with fibrosis, aberrant
      angiogenesis and accelerated progression into heart failure. Therefore, a
      potential therapeutic pathway is to modulate TGFbeta signalling; however, broad
      blockage of TGFbeta signalling may cause unwanted side effects due to its pivotal
      role in tissue homeostasis. We found that leucine-rich alpha-2 glycoprotein 1
      (LRG1) promotes blood vessel formation via regulating the context-dependent
      endothelial TGFbeta signalling. This review will focus on the interaction between
      LRG1 and TGFbeta signalling, their involvement in the pathogenesis of heart
      failure, and the potential for LRG1 to function as a novel therapeutic target.

PMID- 28509986
TI  - Structure and functions of profilins.
AB  - Profilins are small actin-binding proteins found in eukaryotes and certain
      viruses that are involved in cell development, cytokinesis, membrane trafficking,
      and cell motility. Originally identified as an actin sequestering/binding
      protein, profilin has been involved in actin polymerization dynamics. It
      catalyzes the exchange of ADP/ATP in actin and increases the rate of
      polymerization. Profilins also interact with polyphosphoinositides (PPI) and
      proline-rich domains containing proteins. Through its interaction with PPIs,
      profilin has been linked to signaling pathways between the cell membrane and the
      cytoskeleton, while its role in membrane trafficking has been associated with its
      interaction with proline-rich domain-containing proteins. Depending on the
      organism, profilin is present in a various number of isoforms. Four isoforms of
      profilin have been reported in higher organisms, while only one or two isoforms
      are expressed in single-cell organisms. The affinity of these isoforms for their
      ligands varies between isoforms and should therefore modulate their functions.
      However, the significance and the functions of the different isoforms are not yet
      fully understood. The structures of many profilin isoforms have been solved both
      in the presence and the absence of actin and poly-L-proline. These structural
      studies will greatly improve our understanding of the differences and
      similarities between the different profilins. Structural stability studies of
      different profilins are also shedding some light on our understanding of the
      profilin/ligand interactions. Profilin is a multifaceted protein for which a
      dramatic increase in potential functions has been found in recent years; as such,
      it has been implicated in a variety of physiological and pathological processes.

PMID- 28509987
TI  - Corneal collagen-its role in maintaining corneal shape and transparency.
AB  - Corneal collagen has a number of properties that allow it to fulfil its role as
      the main structural component within the tissue. Fibrils are narrow, uniform in
      diameter and precisely organised. These properties are vital to maintain
      transparency and to provide the biomechanical prerequisites necessary to sustain
      shape and provide strength. This review describes the structure and arrangement
      of corneal collagen from the nanoscopic to the macroscopic level, and how this
      relates to the maintenance of the form and transparency of the cornea.

PMID- 28509988
TI  - Vibrational spectroscopic mapping and imaging of tissues and cells.
AB  - Vibrational spectroscopic mapping (point-by-point measurement) and imaging of
      biological samples (cells and tissues) covering Fourier-transform infrared (FTIR)
      and Raman spectroscopies has opened up many exciting new avenues to explore
      biochemical architecture and processes within healthy and diseased cells and
      tissues, including medical diagnostics and drug design.

PMID- 28509991
TI  - Camellia sinensis increased apoptosis on U2OS osteosarcoma cells and wound
      healing potential on NIH3T3 fibroblast cells.
AB  - Camellia sinensis (Cs) is a plant which is rich in polyphenols and has
      antioxidant, antiinflammatory, antimutagenic, anticarcinogenic and antibacterial
      activities. In this study, two different methanol extracts (Cs-I and Cs-II) were
      prepared from the leaf of C. sinensis in order to investigate the wound healing
      and anticancer activities. Total phenolic content and antioxidant activity of the
      extracts were determined. Wound healing effects of Cs extracts were evaluated by
      using Masson's Trichrome Tecnique on NIH3T3 fibroblast cells. Cytotoxic and
      apoptotic effects of the extracts were determined by MTT and AnnexinV-PI assays
      on U2OS osteosarcoma cells. Total phenolic contents and antioxidant activities of
      the extracts were almost the same. The highest concentration (60 ug/mL) of the
      extracts showed significant cytotoxic and apoptotic effects on U2OS cells.
      Especially, the highest apoptotic effect was determined with 60 ug/mL Cs-I
      extract. Significant wound healing potential on NIH3T3 fibroblast cells were
      determined especially with low extract concentrations (0.5, 1 and 5 ug/mL), while
      high extract concentrations showed significant anticancer effects. As a result,
      two Cs leaf extracts exhibited important apoptotic properties and both have wound
      healing potential. However, the Cs-I extract was found more effective on
      apoptotic osteosarcoma cell death and has an increased wound healing potential
      than the Cs-II extract.

PMID- 28509989
TI  - The DNA sequence specificity of bleomycin cleavage in a systematically altered
      DNA sequence.
AB  - Bleomycin is an anti-tumour agent that is clinically used to treat several types
      of cancers. Bleomycin cleaves DNA at specific DNA sequences and recent genome
      wide DNA sequencing specificity data indicated that the sequence 5'-RTGT*AY
      (where T* is the site of bleomycin cleavage, R is G/A and Y is T/C) is
      preferentially cleaved by bleomycin in human cells. Based on this DNA sequence,
      we constructed a plasmid clone to explore this bleomycin cleavage preference. By
      systematic variation of single nucleotides in the 5'-RTGT*AY sequence, we were
      able to investigate the effect of nucleotide changes on bleomycin cleavage
      efficiency. We observed that the preferred consensus DNA sequence for bleomycin
      cleavage in the plasmid clone was 5'-YYGT*AW (where W is A/T). The most highly
      cleaved sequence was 5'-TCGT*AT and, in fact, the seven most highly cleaved
      sequences conformed to the consensus sequence 5'-YYGT*AW. A comparison with
      genome-wide results was also performed and while the core sequence was similar in
      both environments, the surrounding nucleotides were different.

PMID- 28509992
TI  - Learning about "cause" and "effect" through well-designed studies of air quality
      interventions.

PMID- 28509990
TI  - Transient Activation of Reprogramming Transcription Factors Using Protein
      Transduction Facilitates Conversion of Human Fibroblasts Toward Cardiomyocyte
      Like Cells.
AB  - Derivation of cardiomyocytes directly from patients' own fibroblasts could offer
      a new therapeutic approach for those with ischemic heart disease. An essential
      step toward clinical application is to establish safe conversion of human
      fibroblasts into a cardiac fate. Here we aimed to efficiently and safely generate
      cardiomyocytes from human fibroblasts by direct delivery of reprogramming
      recombinant cell permeant form of reprogramming proteins followed by cardio
      inductive signals. Human fetal and adult fibroblasts were transiently exposed to
      transactivator of transcription-fused recombinant OCT4, SOX2, KLF4 and c-MYC for
      2 weeks and then were directly differentiated toward protein-induced
      cardiomyocyte-like cells (p-iCLCs) in a cardiac fate niche, carried out by
      treatment with a set of cardiogenic small molecules (sequential treatment of
      Chir, and IWP-2, SB431542 and purmorphamine). The cells showed cardiac phenotype
      over a period of 3 weeks without first undergoing reprogramming into or through a
      pluripotent intermediate, shown by lack of expression of key pluripotency
      markers. p-iCLCs exhibited cardiac features at both the gene and protein levels.
      Our study provides an alternative method for the generation of p-iCLCs which
      shortcut reprogramming toward allogeneic cardiomyocytes in a safe and efficient
      manner and could facilitate generation of genetic material-free cardiomyocytes.

PMID- 28509993
TI  - Biophysical aspects and biological implications of the interaction of
      benzophenanthridine alkaloids with DNA.
AB  - Benzophenanthridine alkaloids represent a very interesting and significant group
      of natural products that exhibit a broad range of biological and pharmacological
      properties. Among this group of alkaloids, sanguinarine, nitidine, fagaronine,
      and chelerythrine have the potential to form molecular complexes with DNA
      structures and have attracted recent attention for their possible clinical and
      pharmacological utility. This review focuses on the interaction of these
      alkaloids with polymorphic DNA structures (B-form, Z-form, HL-form, and triple
      helical form) reported by several research groups employing various physical
      techniques such as spectrophotometry, spectrofluorimetry, circular dichroism, NMR
      spectroscopy, thermal melting, viscometry as well as thermodynamic analysis by
      isothermal titration calorimetry and differential scanning calorimetry to
      elucidate the mode and mechanism of action at the molecular level to determine
      the structure-activity relationship. DNA binding properties of these alkaloids
      are interpreted in relation to their biological activity.

PMID- 28509994
TI  - Fluorescent membrane probes' behavior in lipid bilayers: insights from molecular
      dynamics simulations.
AB  - Fluorescence spectroscopy and microscopy have been used as tools to study
      membrane biophysics for decades now. Because phospholipids are non-fluorescent,
      the use of extrinsic membrane probes in this context is commonplace. Two major
      points of concern arise regarding this matter, namely the incomplete
      understanding of the probe behavior inside the bilayer and the perturbation of
      the latter resulting from probe incorporation. To this effect, molecular dynamics
      (MD) simulations, by providing detailed atomic-scale information, represent a
      valuable way to characterize the location and dynamics of bilayer-inserted
      membrane probes, as well as the magnitude of perturbation they induce on the host
      lipid structure, and several important classes of reporter molecules have been
      studied in recent years. This article reviews the state of the art of MD
      simulations of bilayer-inserted fluorescent probes, focusing on the information
      that has been obtained from previous studies and hinting at future perspectives
      in this rapidly emerging field.

PMID- 28509995
TI  - Muscle myosin filaments: cores, crowns and couplings.
AB  - Myosin filaments in muscle, carrying the ATPase myosin heads that interact with
      actin filaments to produce force and movement, come in multiple varieties
      depending on species and functional need, but most are based on a common
      structural theme. The now successful journeys to solve the ultrastructures of
      many of these myosin filaments, at least at modest resolution, have not been
      without their false starts and erroneous sidetracks, but the picture now emerging
      is of both diversity in the rotational symmetries of different filaments and a
      degree of commonality in the way the myosin heads are organised in resting
      muscle. Some of the remaining differences may be associated with how the muscle
      is regulated. Several proteins in cardiac muscle myosin filaments can carry
      mutations associated with heart disease, so the elucidation of myosin filament
      structure to understand the effects of these mutations has a clear and topical
      clinical relevance.

PMID- 28509996
TI  - Imaging mass spectrometry: principle and application.
AB  - Imaging mass spectrometry (IMS) is two-dimensional mass spectrometry to visualize
      the spatial distribution of biomolecules, which does not need either separation
      or purification of target molecules, and enables us to monitor not only the
      identification of unknown molecules but also the localization of numerous
      molecules simultaneously. Among the ionization techniques, matrix assisted laser
      desorption/ionization (MALDI) is one of the most generally used for IMS, which
      allows the analysis of numerous biomolecules ranging over wide molecular weights.
      Proper selection and preparation of matrix is essential for successful imaging
      using IMS. Tandem mass spectrometry, which is referred to MSn, enables the
      structural analysis of a molecule detected by the first step of IMS. Applications
      of IMS were initially developed for studying proteins or peptides. At present,
      however, targets of IMS research have expanded to the imaging of small endogenous
      metabolites such as lipids, exogenous drug pharmacokinetics, exploring new
      disease markers, and other new scientific fields. We hope that this new
      technology will open a new era for biophysics.

PMID- 28509997
TI  - Social Desirability Bias and Prevalence of Sexual HIV Risk Behaviors Among People
      Who Use Drugs in Baltimore, Maryland: Implications for Identifying Individuals
      Prone to Underreporting Sexual Risk Behaviors.
AB  - The role of social desirability bias (SDB) in self-reported HIV risk behaviors
      continues to be problematic. This study examined whether SDB was associated with
      self-reported, via audio computer assisted self-interviewing, sexual risk
      behaviors among people who use drugs. The present study was conducted among 559
      participants who reported having a recent sexual partner at their 6-month visit
      of a longitudinal study. Robust Poisson regression was used to model the
      association between SDB and five risk behaviors. Analyses were stratified by
      gender and partner type. Higher scores of SDB were associated with decreased
      reporting of selling sex and having more than one sexual partner. Higher SDB
      scores were associated with increased reporting of always using condoms during
      oral, vaginal, and anal sex. Gender-specific differences were observed. The
      inclusion of a measure of SDB in data collection, along with other strategies,
      can be used to both identify and reduce self-report biases.

PMID- 28509998
TI  - Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator
      Role of ART-Related Knowledge.
AB  - Despite the medical advancements in HIV treatment, realities of side effects are
      faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART).
      Mixed findings have been reported on the association between side effects and ART
      adherence. However, few studies have explored the combined side effects and
      behavior-related information on medication adherence. The aim of the current
      study is to examine moderator role of ART-related knowledge between side effects
      and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from
      October 2012 to August 2013 in China. Of the total sample, 2095 patients had
      received ART and provided ART adherence. Side effects, ART-related knowledge, and
      ART adherence, as well as potential covariates were assessed. The results
      revealed that there was a negative relationship of side effects and ART adherence
      existed among low and medium levels of ART-related knowledge, but not among high
      level of knowledge. Future interventions to promote HIV medication adherence
      should focus on providing behavior-related information education among PLWH.

PMID- 28510002
TI  - The spin label amino acid TOAC and its uses in studies of peptides: chemical,
      physicochemical, spectroscopic, and conformational aspects.
AB  - We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino
      4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide
      synthesis. TOAC was the first spin label probe incorporated in peptides by means
      of a peptide bond. In view of the rigid character of this cyclic molecule and its
      attachment to the peptide backbone via a peptide bond, TOAC incorporation has
      been very useful to analyze backbone dynamics and peptide secondary structure.
      Many of these studies were performed making use of EPR spectroscopy, but other
      physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT
      IR, have been employed. The use of double-labeled synthetic peptides has allowed
      the investigation of their secondary structure. A large number of studies have
      focused on the interaction of peptides, both synthetic and biologically active,
      with membranes. In the latter case, work has been reported on ligands and
      fragments of GPCR, host defense peptides, phospholamban, and beta-amyloid. EPR
      studies of macroscopically aligned samples have provided information on the
      orientation of peptides in membranes. More recent studies have focused on peptide
      protein and peptide-nucleic acid interactions. Moreover, TOAC has been shown to
      be a valuable probe for paramagnetic relaxation enhancement NMR studies of the
      interaction of labeled peptides with proteins. The growth of the number of TOAC
      related publications suggests that this unnatural amino acid will find increasing
      applications in the future.

PMID- 28509999
TI  - Voltage sensor of ion channels and enzymes.
AB  - Placed in the cell membrane (a two-dimensional environment), ion channels and
      enzymes are able to sense voltage. How these proteins are able to detect the
      difference in the voltage across membranes has attracted much attention, and at
      times, heated debate during the last few years. Sodium, Ca2+ and K+ voltage
      dependent channels have a conserved positively charged transmembrane (S4) segment
      that moves in response to changes in membrane voltage. In voltage-dependent
      channels, S4 forms part of a domain that crystallizes as a well-defined structure
      consisting of the first four transmembrane (S1-S4) segments of the channel
      forming protein, which is defined as the voltage sensor domain (VSD). The VSD is
      tied to a pore domain and VSD movements are allosterically coupled to the pore
      opening to various degrees, depending on the type of channel. How many charges
      are moved during channel activation, how much they move, and which are the
      molecular determinants that mediate the electromechanical coupling between the
      VSD and the pore domains are some of the questions that we discuss here. The VSD
      can function, however, as a bona fide proton channel itself, and, furthermore,
      the VSD can also be a functional part of a voltage-dependent phosphatase.

PMID- 28510000
TI  - Actin in striated muscle: recent insights into assembly and maintenance.
AB  - Striated muscle cells are characterised by a para-crystalline arrangement of
      their contractile proteins actin and myosin in sarcomeres, the basic unit of the
      myofibrils. A multitude of proteins is required to build and maintain the
      structure of this regular arrangement as well as to ensure regulation of
      contraction and to respond to alterations in demand. This review focuses on the
      actin filaments (also called thin filaments) of the sarcomere and will discuss
      how they are assembled during myofibrillogenesis and in hypertrophy and how their
      integrity is maintained in the working myocardium.

PMID- 28510004
TI  - Non fitting based FRET-FLIM analysis approaches applied to quantify protein
      protein interactions in live cells.
AB  - New imaging methodologies in quantitative fluorescence microscopy and nanoscopy
      have been developed in the last few years and are beginning to be extensively
      applied to biological problems, such as the localization and quantification of
      protein interactions. Fluorescence resonance energy transfer (FRET) detected by
      fluorescence lifetime imaging microscopy (FLIM) is currently employed not only in
      biophysics or chemistry but also in bio-medicine, thanks to new advancements in
      technology and also new developments in data treatment. FRET-FLIM can be a very
      useful tool to ascertain protein interactions occurring in single living cells.
      In this review, we stress the importance of increasing the acquisition speed when
      working in vivo employing Time-Domain FLIM. The development of the new
      mathematical-based non-fitting methods allows the determining of the fraction of
      interacting donor without the requirement of high count statistics, and thus
      allows the performing of high speed acquisitions in FRET-FLIM to still be
      quantitative.

PMID- 28510003
TI  - SPontaneous Oscillatory Contraction (SPOC): auto-oscillations observed in
      striated muscle at partial activation.
AB  - Striated muscle is well known to exist in either of two states-contraction or
      relaxation-under the regulation of Ca2+ concentration. Described here is a less
      well-known third, intermediate state induced under conditions of partial
      activation, known as SPOC (SPontaneous Oscillatory Contraction). This state is
      characterised by auto-oscillation between rapid-lengthening and slow-shortening
      phases. Notably, SPOC occurs in skinned muscle fibres and is therefore not the
      result of fluctuating Ca2+ levels, but is rather an intrinsic and fundamental
      phenomenon of the actomyosin motor. Summarised in this review are the
      experimental data on SPOC and its fundamental mechanism. SPOC presents a novel
      technique for studying independent communication and coordination between
      sarcomeres. In cardiac muscle, this auto-oscillatory property may work in concert
      with electro-chemical signalling to coordinate the heartbeat. Further, SPOC may
      represent a new way of demonstrating functional defects of sarcomeres in human
      heart failure.

PMID- 28510001
TI  - Proteoliposomes in nanobiotechnology.
AB  - Proteoliposomes are systems that mimic lipid membranes (liposomes) to which a
      protein has been incorporated or inserted. During the last decade, these systems
      have gained prominence as tools for biophysical studies on lipid-protein
      interactions as well as for their biotechnological applications. Proteoliposomes
      have a major advantage when compared with natural membrane systems, since they
      can be obtained with a smaller number of lipidic (and protein) components,
      facilitating the design and interpretation of certain experiments. However, they
      have the disadvantage of requiring methodological standardization for
      incorporation of each specific protein, and the need to verify that the
      reconstitution procedure has yielded the correct orientation of the protein in
      the proteoliposome system with recovery of its functional activity. In this
      review, we chose two proteins under study in our laboratory to exemplify the
      steps necessary for the standardization of the reconstitution of membrane
      proteins in liposome systems: (1) alkaline phosphatase, a protein with a
      glycosylphosphatidylinositol anchor, and (2) Na,K-ATPase, an integral membrane
      protein. In these examples, we focus on the production of the specific
      proteoliposomes, as well as on their biochemical and biophysical
      characterization, with emphasis on studies of lipid-protein interactions. We
      conclude the chapter by highlighting current prospects of this technology for
      biotechnological applications, including the construction of nanosensors and of a
      multi-protein nanovesicular biomimetic to study the processes of initiation of
      skeletal mineralization.

PMID- 28510005
TI  - Respiratory system dynamical mechanical properties: modeling in time and
      frequency domain.
AB  - The mechanical properties of the respiratory system are important determinants of
      its function and can be severely compromised in disease. The assessment of
      respiratory system mechanical properties is thus essential in the management of
      some disorders as well as in the evaluation of respiratory system adaptations in
      response to an acute or chronic process. Most often, lungs and chest wall are
      treated as a linear dynamic system that can be expressed with differential
      equations, allowing determination of the system's parameters, which will reflect
      the mechanical properties. However, different models that encompass nonlinear
      characteristics and also multicompartments have been used in several approaches
      and most specifically in mechanically ventilated patients with acute lung injury.
      Additionally, the input impedance over a range of frequencies can be assessed
      with a convenient excitation method allowing the identification of the mechanical
      characteristics of the central and peripheral airways as well as lung periphery
      impedance. With the evolution of computational power, the airway pressure and
      flow can be recorded and stored for hours, and hence continuous monitoring of the
      respiratory system mechanical properties is already available in some mechanical
      ventilators. This review aims to describe some of the most frequently used models
      for the assessment of the respiratory system mechanical properties in both time
      and frequency domain.

PMID- 28510007
TI  - Response to editorial: Diagnosing carotid near-occlusion with 1-mm side-to-side
      asymmetry: a tough task made too easy.

PMID- 28510006
TI  - Evaluation of the DSM-5 Severity Specifier for Bulimia Nervosa in Treatment
      Seeking Youth.
AB  - A new severity specifier for bulimia nervosa (BN), based on the frequency of
      inappropriate weight compensatory behaviours (e.g., laxative misuse, self-induced
      vomiting, fasting, diuretic misuse, and excessive exercise), has been added to
      the most recent (fifth) edition of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-5) as a means of addressing variability and heterogeneity
      in the severity of the disorder. While existing research provides support for the
      DSM-5 severity specifier for BN in adult patients, evidence for its validity and
      clinical utility in youth is currently lacking. To address this gap, data from
      272 treatment-seeking adolescents with DSM-5 BN (94.2% female, M age = 15.3
      years, SD 1.7) were analysed to examine whether these patients, sub-grouped based
      on the DSM-5 severity definitions, would show meaningful differences in a broad
      range of clinical variables and demographic and physical characteristics.
      Analyses revealed that participants categorized with mild, moderate, severe, and
      extreme severity of BN significantly differed from each other in 15 variables
      regarding eating disorder pathological features and putative maintenance factors
      (i.e., core low self-esteem, perfectionism, social appearance anxiety, body
      surveillance, and mood intolerance), health-related quality of life and comorbid
      psychiatric (i.e., affective and anxiety) disorders (large effect sizes). Between
      group differences in demographics, body mass index, or age-of-BN onset were not
      observed. Collectively, our findings provide support for the utility of the
      frequency of inappropriate weight compensatory behaviours as a severity indicator
      for BN and suggest that age-at-onset of BN is probably more disorder- than
      severity-dependent. Implications for future research are outlined.

PMID- 28510008
TI  - Plasma modified surfaces for covalent immobilization of functional biomolecules
      in the absence of chemical linkers: towards better biosensors and a new
      generation of medical implants.
AB  - Plasma modification and plasma polymer deposition are valuable technologies for
      the preparation of surfaces for the covalent binding of biomolecules for
      applications such as biosensors, medical prostheses, and diagnostic devices as
      well as surfaces for enzyme-mediated reactions. Covalency is conveniently tested
      by the ability of the surface to retain the attached molecules after vigorous
      washing with sodium dodecyl sulphate (SDS). Covalency is indicated if the
      fraction of protein retained lies above the curve characteristic of
      physisorption. Confidence in covalency is strengthened when the washing protocol
      is aggressive enough to remove all adsorbed protein from a control significantly
      more hydrophobic than the test surface. The use of linker chemistry to space the
      molecules from the surface is in some cases beneficial. However, the use of
      linker chemistry is not necessary to retain molecular function for long periods
      when the polymer surface is modified by energetic bombardment. The energetic
      bombardment retains hydrophilicity of the surface by crosslinking the subsurface,
      and this appears to facilitate retention of protein function. Energetic
      bombardment also increases the functional life of molecules immobilized and then
      freeze dried on plasma-modified surfaces. Analysis of the surfaces shows that the
      covalent binding mechanism is related to the presence of free radicals on the
      surface and in the subsurface regions. The unpaired electrons associated with the
      radicals appear to be mobile within the modified region and can diffuse to the
      surface to take part in binding interactions. Proactive implantable devices can
      make use of these principles of covalent attachment by seeding the surface of an
      implant with a biomolecule that elicits the desired interaction with cells and
      prevents undesirable responses.

PMID- 28510010
TI  - Advanced magnetic resonance imaging techniques to better understand multiple
      sclerosis.
AB  - Magnetic resonance imaging (MRI) has considerably improved the diagnosis and
      monitoring of multiple sclerosis (MS). Conventional MRI such as T2-weighted and
      gadolinium-enhanced T1-weighted sequences detect focal lesions of the white
      matter, damage of the blood-brain barrier, and tissue loss and inflammatory
      activity within lesions. However, these conventional MRI metrics lack the
      specificity required for characterizing the underlying pathophysiology,
      especially diffuse damage occurring throughout the whole central nervous system.
      To overcome these limitations, advanced MRI techniques have been developed to get
      more sensitive and specific parameters of focal and diffuse brain damage. Among
      these techniques, magnetization transfer imaging, diffusion MRI, functional MRI,
      and magnetic resonance spectroscopy are the most significant. In this article, we
      provide an overview of these advanced MRI techniques and their contribution to
      the better characterization and understanding of MS.

PMID- 28510009
TI  - Conventional myosins - unconventional functions.
AB  - While the discovery of unconventional myosins raised expectations that their
      actions were responsible for most aspects of actin-based cell motility, few
      anticipated the wide range of cellular functions that would remain the purview of
      conventional two-headed myosins. The three nonsarcomeric, cellular myosins-M2A,
      M2B and M2C-participate in diverse roles including, but not limited to: neuronal
      dynamics, axon guidance and synaptic transmission; endothelial cell migration;
      cell adhesion, polarity, fusion and cytokinesis; vesicle trafficking and viral
      egress. These three conventional myosins each take on specific, differing
      functional roles during development and maturity, characteristic of each cell
      lineage; exact roles depend on the developmental stage of the cell, cellular
      location, upstream regulatory controls, relative isoform expression, orientation
      and associated state of the actin cytoscaffolds in which these myosins operate.
      Here, we discuss the separate yet related roles that characterise the actions of
      M2A, M2B and M2C in various cell types and show that these conventional myosins
      are responsible for functions as unconventional as any performed by
      unconventional myosins.

PMID- 28510012
TI  - A note on the career of Donald J Winzor.

PMID- 28510011
TI  - Dynamic light scattering: a practical guide and applications in biomedical
      sciences.
AB  - Dynamic light scattering (DLS), also known as photon correlation spectroscopy
      (PCS), is a very powerful tool for studying the diffusion behaviour of
      macromolecules in solution. The diffusion coefficient, and hence the hydrodynamic
      radii calculated from it, depends on the size and shape of macromolecules. In
      this review, we provide evidence of the usefulness of DLS to study the
      homogeneity of proteins, nucleic acids, and complexes of protein-protein or
      protein-nucleic acid preparations, as well as to study protein-small molecule
      interactions. Further, we provide examples of DLS's application both as a
      complementary method to analytical ultracentrifugation studies and as a screening
      tool to validate solution scattering models using determined hydrodynamic radii.

PMID- 28510013
TI  - NMR magnetization-transfer analysis of rapid membrane transport in human
      erythrocytes.
AB  - Nuclear magnetic resonance (NMR) magnetization-transfer (MT) experiments provide
      a convenient tool for studying rapid sub-second membrane-transport processes in
      situ in metabolically active cells. These experiments are used with membrane
      permeable substances when separate (resolved) NMR signals are observed from their
      populations inside and outside the cells. Here, we provide a description of the
      theory and practice of the most common NMR MT experiments that have been used to
      study membrane-transport processes in human erythrocytes (red blood cells; RBCs).
      The procedures, involved in the analysis of the experimental data for defining
      mechanisms of transport, and for estimating values of kinetic parameters in the
      corresponding mathematical models, are given special attention.

PMID- 28510016
TI  - Big ideas from "small science".

PMID- 28510014
TI  - Biosensor binding data and its applicability to the determination of active
      concentration.
AB  - Protein concentration data are required for understanding protein interactions
      and are a prerequisite for the determination of affinity and kinetic properties.
      It is vital for the judgment of protein quality and for monitoring the effect of
      therapeutic agents. Protein concentration values are typically obtained by
      comparison to a standard and derived from a standard curve. The use of a protein
      standard is convenient, but may not give reliable results if samples and
      standards behave differently. In other cases, a standard preparation may not be
      available and has to be established and validated. Using surface plasmon
      resonance (SPR) biosensors, an alternative concentration method is possible. This
      method is called calibration-free concentration analysis (CFCA); it generates
      active concentration data directly and without the use of a standard. The active
      concentration of a protein is defined through its interaction with its binding
      partner. This concentration can differ from the total protein concentration if
      some protein fraction is incapable of binding. If a protein has several different
      binding sites, active concentration data can be established for each binding site
      using site-specific interaction partners. This review will focus on CFCA
      analysis. It will reiterate the theory of CFCA and describe how CFCA has been
      applied in different research segments. The major part of the review will,
      however, try to set expectations on CFCA and discuss how CFCA can be further
      developed for absolute and relative concentration measurements.

PMID- 28510017
TI  - Charge matters.

PMID- 28510015
TI  - Dissociative mechanism for irreversible thermal denaturation of oligomeric
      proteins.
AB  - Protein stability is a fundamental characteristic essential for understanding
      conformational transformations of the proteins in the cell. When using protein
      preparations in biotechnology and biomedicine, the problem of protein stability
      is of great importance. The kinetics of denaturation of oligomeric proteins may
      have characteristic properties determined by the quaternary structure. The
      kinetic schemes of denaturation can include the multiple stages of conformational
      transitions in the protein oligomer and stages of reversible dissociation of the
      oligomer. In this case, the shape of the kinetic curve of denaturation or the
      shape of the melting curve registered by differential scanning calorimetry can
      vary with varying the protein concentration. The experimental data illustrating
      dissociative mechanism for irreversible thermal denaturation of oligomeric
      proteins have been summarized in the present review. The use of test systems
      based on thermal aggregation of oligomeric proteins for screening of agents
      possessing anti-aggregation activity is discussed.

PMID- 28510018
TI  - A Hilly path through the thermodynamics and statistical mechanics of protein
      solutions.
AB  - The opus of Don Winzor in the fields of physical and analytical biochemistry is a
      major component of that certain antipodean approach to this broad area of
      research that blossomed in the second half of the twentieth century. The need to
      formulate problems in terms of thermodynamic nonideality posed the challenge of
      describing a clear route from molecular interactions to the parameters that
      biochemists routinely measure. Mapping out this route required delving into the
      statistical mechanics of solutions of macromolecules, and at every turn
      mathematically complex, rigorous, general results that had previously been
      derived previously, often by Terrell Hill, came to the fore. Central to this work
      were the definition of the "thermodynamic activity", the pivotal position of the
      polynomial expansion of the osmotic pressure in terms of molar concentration and
      the relationship of virial coefficients to details of the forces between limited
      size groups of interacting molecules. All of this was richly exploited in the
      task of taking account of excluded volume and electrostatic interactions,
      especially in the use of sedimentation equilibrium to determine values of
      constants for molecular association reactions. Such an approach has proved
      relevant to the study of molecular interactions generally, even those between the
      main macromolecular solute and components of the solvent, by using techniques
      such as exclusion and affinity chromatography as well as light scattering.

PMID- 28510019
TI  - Six decades of research in physical biochemistry.

PMID- 28510021
TI  - Molecular assembly and structure of the bacteriophage T4 tail.
AB  - The tail of bacteriophage T4 undergoes large structural changes upon infection
      while delivering the phage genome into the host cell. The baseplate is located at
      the distal end of the contractile tail and plays a central role in transmitting
      the signal to the tail sheath that the tailfibers have been adsorbed by a host
      bacterium. This then triggers the sheath contraction. In order to understand the
      mechanism of assembly and conformational changes of the baseplate upon infection,
      we have determined the structure of an in vitro assembled baseplate through the
      three-dimensional reconstruction of cryo-electron microscopy images to a
      resolution of 3.8 A from electron micrographs. The atomic structure was fitted to
      the baseplate structure before and after sheath contraction in order to elucidate
      the conformational changes that occur after bacteriophage T4 has attached itself
      to a cell surface. The structure was also used to investigate the protease
      digestion of the assembly intermediates and the mutation sites of the tail genes,
      resulting in a number of phenotypes.

PMID- 28510022
TI  - Aspects of protein-DNA interactions: a review of quantitative thermodynamic
      theory for modelling synthetic circuits utilising LacI and CI repressors, IPTG
      and the reporter gene lacZ.
AB  - Protein-DNA interactions are central to the control of gene expression across all
      forms of life. The development of approaches to rigorously model such
      interactions has often been hindered both by a lack of quantitative binding data
      and by the difficulty in accounting for parameters relevant to the intracellular
      situation, such as DNA looping and thermodynamic non-ideality. Here, we review
      these considerations by developing a thermodynamically based mathematical model
      that attempts to simulate the functioning of an Escherichia coli expression
      system incorporating two of the best characterised prokaryotic DNA binding
      proteins, Lac repressor and lambda CI repressor. The key aim was to reproduce
      experimentally observed reporter gene activities arising from the expression of
      either wild-type CI repressor or one of three positive-control CI mutants. The
      model considers the role of several potentially important, but sometimes
      neglected, biochemical features, including DNA looping, macromolecular crowding
      and non-specific binding, and allowed us to obtain association constants for the
      binding of CI and its variants to a specific operator sequence.

PMID- 28510020
TI  - Foreword to 'Quantitative and analytical relations in biochemistry'-a special
      issue in honour of Donald J. Winzor's 80th birthday.
AB  - The purpose of this special issue is to honour Professor Donald J. Winzor's long
      career as a researcher and scientific mentor, and to celebrate the milestone of
      his 80th birthday. Throughout his career, Don has been renowned for his
      development of clever approximations to difficult quantitative relations
      governing a range of biophysical measurements. The theme of this special issue,
      'Quantitative and analytical relations in biochemistry', was chosen to reflect
      this aspect of Don's scientific approach.

PMID- 28510023
TI  - Protein-RNA interactions: structural biology and computational modeling
      techniques.
AB  - RNA-binding proteins are functionally diverse within cells, being involved in RNA
      metabolism, translation, DNA damage repair, and gene regulation at both the
      transcriptional and post-transcriptional levels. Much has been learnt about their
      interactions with RNAs through structure determination techniques and
      computational modeling. This review gives an overview of the structural data
      currently available for protein-RNA complexes, and discusses the technical issues
      facing structural biologists working to solve their structures. The review
      focuses on three techniques used to solve the 3-dimensional structure of protein
      RNA complexes at atomic resolution, namely X-ray crystallography, solution
      nuclear magnetic resonance (NMR) and cryo-electron microscopy (cryo-EM). The
      review then focuses on the main computational modeling techniques that use these
      atomic resolution data: discussing the prediction of RNA-binding sites on unbound
      proteins, docking proteins, and RNAs, and modeling the molecular dynamics of the
      systems. In conclusion, the review looks at the future directions this field of
      research might take.

PMID- 28510025
TI  - Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms.
AB  - Substantial progress in understanding thermal transduction in peripheral sensory
      nerve endings was achieved with the recent cloning of six thermally gated ion
      channels from the TRP (transient receptor potential) super-family. Two of these
      channels, TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1), are expressed in
      dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons, are activated by
      various degrees of cooling, and are candidates for mediating gentle cooling and
      noxious cold, respectively. However, accumulating evidence suggests that more
      than just these two channels are involved in cold sensing in mammals. A recent
      report described a critical role of the voltage-gated tetrodotoxin-resistant
      sodium channel Nav1.8 in perceiving intense cold and noxious stimuli at cold
      temperatures. Other ion channels, such as two-pore domain background potassium
      channels (K2P), are known to be expressed in peripheral nerves, have pronounced
      temperature dependence, and may contribute to cold sensing and/or cold
      hypersensitivity in pain states. This article reviews the evidence supporting a
      role for each of these channels in cold transduction, focusing on their
      biophysical properties, expression pattern, and modulation by pro-inflammatory
      mediators.

PMID- 28510024
TI  - Mineralization and non-ideality: on nature's foundry.
AB  - Understanding how ions, ion-clusters and particles behave in non-ideal
      environments is a fundamental question concerning planetary to atomic scales. For
      biomineralization phenomena wherein diverse inorganic and organic ingredients are
      present in biological media, attributing biomaterial composition and structure to
      the chemistry of singular additives may not provide a holistic view of the
      underlying mechanisms. Therefore, in this review, we specifically address the
      consequences of physico-chemical non-ideality on mineral formation. Influences of
      different forms of non-ideality such as macromolecular crowding, confinement and
      liquid-like organic phases on mineral nucleation and crystallization in
      biological environments are presented. Novel prospects for the additive
      controlled nucleation and crystallization are accessible from this biophysical
      view. In this manner, we show that non-ideal conditions significantly affect the
      form, structure and composition of biogenic and biomimetic minerals.

PMID- 28510026
TI  - Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part
      2 - In vivo developments and present clinical applications.
AB  - Gene electrotransfer can be obtained not just on single cells in diluted
      suspension. For more than 10 years, this is a quasi routine strategy in tissue on
      the living animal and a few clinical trials have now been approved. New problems
      have been brought by the close contacts of cells in tissue both on the local
      field distribution and on the access of DNA to target cells. They need to be
      solved to provide a further improvement in the efficacy and safety of protein
      expression. There is a competition between gene transfer and cell destruction.
      Nevertheless, present results are indicative that electrotransfer is a promising
      approach for gene therapy. High level and long-lived expression of proteins can
      be obtained in muscles. This is used for a successful method of
      electrovaccination.

PMID- 28510028
TI  - Creating robust, reliable, clinically relevant classifiers from spectroscopic
      data.
AB  - I describe in detail the intimately connected feature extraction and classifier
      development stages of the data-driven Statistical Classification Strategy (SCS)
      and compare them with current practice used in MR spectroscopy. We initially
      created the SCS for the analysis of MR and IR spectra of biofluids and tissues,
      and subsequently extended it to analyze biomedical data in general. I focus on
      explaining how to extract discriminatory spectral features and create robust
      classifiers that can reliably discriminate diseases and disease states. I discuss
      our approach to identifying features that retain spectral identity and
      provisionally relate these features, averaged subregions of the spectra, to
      specific chemical entities ("metabolites"). Particular emphasis is placed on
      describing the steps required to help create classifiers whose accuracy doesn't
      deteriorate significantly when presented with new, unknown samples. A simple but
      powerful extension of the discovered features to detect metabolite-metabolite
      (feature-feature) interactions is also sketched. I contrast the advantages and
      disadvantages of using either spectral signatures or explicit metabolite
      concentrations derived from the spectra as sets of discriminatory features. At
      present, no clear-cut preference is obvious and more objective comparisons will
      be needed. Finally, I argue that clinical requirements and exigencies strongly
      suggest adopting a two-phase approach to diagnosis/prognosis. In the first phase
      the emphasis ought to be on providing as accurate a diagnosis as possible,
      without any attempt to identify "biomarkers." That should be the goal of the
      second, research phase, with a view of providing prognosis on disease
      progression.

PMID- 28510030
TI  - Tri-modal regulation of cardiac muscle relaxation; intracellular calcium decline,
      thin filament deactivation, and cross-bridge cycling kinetics.
AB  - Cardiac muscle relaxation is an essential step in the cardiac cycle. Even when
      the contraction of the heart is normal and forceful, a relaxation phase that is
      too slow will limit proper filling of the ventricles. Relaxation is too often
      thought of as a mere passive process that follows contraction. However, many
      decades of advancements in our understanding of cardiac muscle relaxation have
      shown it is a highly complex and well-regulated process. In this review, we will
      discuss three distinct events that can limit the rate of cardiac muscle
      relaxation: the rate of intracellular calcium decline, the rate of thin-filament
      de-activation, and the rate of cross-bridge cycling. Each of these processes are
      directly impacted by a plethora of molecular events. In addition, these three
      processes interact with each other, further complicating our understanding of
      relaxation. Each of these processes is continuously modulated by the need to
      couple bodily oxygen demand to cardiac output by the major cardiac physiological
      regulators. Length-dependent activation, frequency-dependent activation, and beta
      adrenergic regulation all directly and indirectly modulate calcium decline, thin
      filament deactivation, and cross-bridge kinetics. We hope to convey our
      conclusion that cardiac muscle relaxation is a process of intricate checks and
      balances, and should not be thought of as a single rate-limiting step that is
      regulated at a single protein level. Cardiac muscle relaxation is a system level
      property that requires fundamental integration of three governing systems:
      intracellular calcium decline, thin filament deactivation, and cross-bridge
      cycling kinetics.

PMID- 28510027
TI  - Single-molecule Forster resonance energy transfer studies of RNA structure,
      dynamics and function.
AB  - Single-molecule fluorescence microscopy experiments on RNA molecules brought to
      light the highly complex dynamics of key biological processes, including RNA
      folding, catalysis of ribozymes, ligand sensing of riboswitches and aptamers, and
      protein synthesis in the ribosome. By using highly advanced biophysical
      spectroscopy techniques in combination with sophisticated biochemical synthesis
      approaches, molecular dynamics of individual RNA molecules can be observed in
      real time and under physiological conditions in unprecedented detail that cannot
      be achieved with bulk experiments. Here, we review recent advances in RNA folding
      and functional studies of RNA and RNA-protein complexes addressed by using single
      molecule Forster (fluorescence) resonance energy transfer (smFRET) technique.

PMID- 28510031
TI  - The structure and function of thioester-containing proteins in arthropods.
AB  - Thioester-containing proteins (TEPs) form an ancient and diverse family of
      secreted proteins that play central roles in the innate immune response. Two
      families of TEPs, complement factors and alpha2-macroglobulins, have been known
      and studied in vertebrates for many years, but only in the last decade have
      crystal structures become available. In the same period, the presence of two
      additional classes of TEPs has been revealed in arthropods. In this review, we
      discuss the common structural features TEPs and how this knowledge can be applied
      to the many arthropod TEPs of unknown function. TEPs perform a wide variety of
      functions that are driven by different quaternary structures and protein-protein
      interactions between a common set of folded domains. A common theme is regulated
      conformational change triggered by proteolysis. Structure-function analysis of
      the diverse arthropod TEPs may identify not just new mechanisms in innate
      immunity but also interfaces between immunity, development and cell death.

PMID- 28510029
TI  - Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part
      1- Biophysical mechanisms.
AB  - Electropulsation is one of the nonviral methods successfully used to deliver
      genes into living cells in vitro and in vivo. This approach shows promise in the
      field of gene and cellular therapies. The present review focuses on the processes
      supporting gene electrotransfer in vitro. In the first part, we will report the
      events occurring before, during, and after pulse application in the specific
      field of plasmid DNA electrotransfer at the cell level. A critical discussion of
      the present theoretical considerations about membrane electropermeabilization and
      the transient structures involved in the plasmid uptake follows in a second part.

PMID- 28510033
TI  - The Antagonistic Effect of Selenium on Cadmium-Induced Damage and mRNA Levels of
      Selenoprotein Genes and Inflammatory Factors in Chicken Kidney Tissue.
AB  - Selenium (Se) is a necessary trace mineral in the diet of humans and animals.
      Cadmium (Cd) is a toxic heavy metal that can damage animal organs, especially the
      kidneys. Antagonistic interactions between Se and Cd have been reported in
      previous studies. However, little is known about the effects of Se against Cd
      toxicity and on the mRNA levels of 25 selenoprotein genes and inflammatory
      factors in chicken kidneys. In the current study, we fed chickens with a Se
      treated, Cd-treated, or Se/Cd treated diet for 90 days. We then analyzed the mRNA
      expression of inflammatory factors (including prostaglandin E synthase (PTGES),
      nuclear factor-kappa B (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), and
      cyclooxygenase-2 (COX-2)) and 25 selenoprotein genes (Gpx1, Gpx2, Gpx3, Gpx4,
      Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, SPS2, Sepp1, SelPb, Sep15, Selh, Seli,
      Selm, Selo, Sels, Sepx1, Selu, Selk, Selw, Seln, Selt). The results demonstrated
      that Cd exposure increased the Cd content in the chicken kidneys, renal tubular
      epithelial cells underwent denaturation and necrosis, and the tubules became
      narrow or disappeared. However, Se supplementation reduced the Cd content in
      chicken kidneys and induced normal development of renal tubular epithelial cells.
      In addition, we also observed that Se alleviated the Cd-induced increase in the
      mRNA levels of inflammatory factors and ameliorated the Cd-induced downtrend in
      the mRNA levels of 25 selenoprotein genes in chicken kidneys.

PMID- 28510034
TI  - Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant
      Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry
      Registry.
AB  - Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by
      mutations in the gene encoding alpha-galactosidase, GLA. In patients with Fabry
      disease, glycosphingolipids accumulate in various cell types, triggering a range
      of cellular and tissue responses that result in a wide spectrum of organ
      involvement. Although variable, gastrointestinal symptoms are among the most
      common and significant early clinical manifestations; they tend to persist into
      adulthood if left untreated. To further understand the effects of sustained
      enzyme replacement therapy (ERT) with agalsidase beta on gastrointestinal
      symptoms in heterozygotes, a data analysis of female patients enrolled in the
      Fabry Registry was conducted. To be included, females of any age must have
      received agalsidase beta (average dose 1.0 mg/kg every 2 weeks) for at least 2.5
      years. Measured outcomes were self-reported gastrointestinal symptoms (abdominal
      pain, diarrhea). Outcomes at baseline and last follow-up, and their change from
      baseline to last follow-up, were assessed. Relevant data were available for 168
      female patients. Mean age at the start of ERT was 43 years and mean treatment
      duration 5.7 years. Baseline pre-treatment abdominal pain was reported by 45% of
      females and diarrhea by 39%. At last follow-up, 31% reported abdominal pain (p <
      0.01) and 27% diarrhea (p < 0.01). The results of this Fabry Registry analysis
      suggest that while on sustained treatment with agalsidase beta (1.0 mg/kg every 2
      weeks), both abdominal pain and diarrhea improved in many female patients with
      Fabry disease.

PMID- 28510032
TI  - Kidney stone analysis techniques and the role of major and trace elements on
      their pathogenesis: a review.
AB  - Kidney stone disease is a polygenic and multifactorial disorder with a worldwide
      distribution, and its incidence and prevalence are increasing. Although
      significant progress has been made in recent years towards identifying the
      specific factors that contribute to the formation of kidney stone, many questions
      on the pathogenesis of kidney stones remain partially or completely unanswered.
      However, none of the proposed mechanisms specifically consider the role(s) of the
      trace elements and, consequently, the contribution of trace constituents to the
      pathogenesis of kidney stones remains unclear and under debate. The findings of
      some studies seem to support a role for some major and trace elements in the
      initiation of stone crystallization, including as a nucleus or nidus for the
      formation of the stone or simply as a contaminant of the stone structure. Thus,
      the analysis of kidney stones is an important component of investigations on
      nephrolithiasis in order to understand the role of trace constituents in the
      formation of kidney stones and to formulate future strategies for the treatment
      and prevention of stone formation and its recurrence. The aim of this review is
      to compare and evaluate the methods/procedures commonly used in the analysis of
      urinary calculi. We also highlight the role of major and trace elements in the
      pathogenesis of kidney stones.

PMID- 28510036
TI  - [Caring for patients-but carefully of course : Structured Handover].

PMID- 28510035
TI  - Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not
      in GLUT1 Deficiency.
AB  - OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms
      associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures
      in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because
      high-fat diet raises serious compliance issues, we investigated if oral L,D-3
      hydroxybutyrate administration could be as effective as ketogenic diet in PDHD
      and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of
      KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. RESULTS:
      In GLUT1-DS patients, we observed clinical deterioration including increased
      frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased
      after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed
      clinical improvement as dystonic crises and fatigability decreased under basal
      metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has
      largely replaced the ketogenic diet, with the latter that is mostly resumed only
      during febrile illness. Positive direct effects on energy metabolism in PDHD
      patients were suggested by negative correlation between ketonemia and lactatemia
      (r 2 = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of
      CO2 production after 14C-labeled 3-hydroxybutyrate supplementation was consistent
      with improved Krebs cycle activity. However, except in one patient, ketonemia
      tended to be lower with 3-hydroxybutyrate administration compared to ketogenic
      diet. CONCLUSION: 3-hydroxybutyrate may be an adjuvant treatment to ketogenic
      diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless,
      ketogenic diet is still necessary in PDHD patients during febrile illness.

PMID- 28510038
TI  - MOLS sampling and its applications in structural biophysics.
AB  - This review describes the MOLS method and its applications. This computational
      method has been developed in our laboratory primarily to explore the
      conformational space of small peptides and identify features of interest,
      particularly the minima, i.e., the low energy conformations. A systematic "brute
      force" search through the vast conformational space for such features faces the
      insurmountable problem of combinatorial explosion, whilst other techniques, e.g.,
      Monte Carlo searches, are somewhat limited in their region of exploration and may
      be considered inexhaustive. The MOLS method, on the other hand, uses a sampling
      technique commonly employed in experimental design theory to identify a small
      sample of the conformational space that nevertheless retains information about
      the entire space. The information is extracted using a technique that is a
      variant of the self-consistent mean field technique, which has been used to
      identify, for example, the optimal set of side-chain conformations in a protein.
      Applications of the MOLS method to understand peptide structure, predict the
      structures of loops in proteins, predict three-dimensional structures of small
      proteins, and arrive at the best conformation, orientation, and positions of a
      small molecule ligand in a protein receptor site have all yielded satisfactory
      results.

PMID- 28510037
TI  - Optical imaging of nanoscale cellular structures.
AB  - Visualization of subcellular structures and their temporal evolution is of utmost
      importance to understand a vast range of biological processes. Optical microscopy
      is the method of choice for imaging live cells and tissues; it is minimally
      invasive, so processes can be observed over extended periods of time without
      generating artifacts due to intense light irradiation. The use of fluorescence
      microscopy is advantageous because biomolecules or supramolecular structures of
      interest can be labeled specifically with fluorophores, so the images reveal
      information on processes involving only the labeled molecules. The key
      restriction of optical microscopy is its moderate resolution, which is limited to
      about half the wavelength of light (~200 nm) due to fundamental physical laws
      governing wave optics. Consequently, molecular processes taking place at spatial
      scales between 1 and 100 nm cannot be studied by regular optical microscopy. In
      recent years, however, a variety of super-resolution fluorescence microscopy
      techniques have been developed that circumvent the resolution limitation. Here,
      we present a brief overview of these techniques and their application to cellular
      biophysics.

PMID- 28510039
TI  - Synaptopodin family of natively unfolded, actin binding proteins: physical
      properties and potential biological functions.
AB  - The synaptopodin family of proteins consists of at least 3 members: synaptopodin,
      the synaptopodin 2 proteins, and the synaptopodin 2-like proteins. Each family
      member has at least 3 isoforms that are produced by alternative splicing.
      Synaptopodin family members are basic proteins that are rich in proline and have
      little regular 2 degrees  or 3 degrees  structure at physiological temperature,
      pH and ionic strength. Like other natively unfolded proteins, synaptopodin family
      members have multiple binding partners including actin and other actin-binding
      proteins. Several members of the synaptopodin family have been shown to stimulate
      actin polymerization and to bundle actin filaments either on their own or in
      collaboration with other proteins. Synaptopodin 2 has been shown to accelerate
      nucleation of actin filament formation and to induce actin bundling. The actin
      polymerization activity is inhibited by Ca2+-calmodulin. Synaptopodin 2 proteins
      are localized in Z-bands of striated and heart muscle and dense bodies of smooth
      muscle cells. Depending on the developmental status and stress, at least one
      member of the synaptopodin family can occupy nuclei of some cells. Members of the
      synaptopodin 2 subfamily have been implicated in cancers.

PMID- 28510040
TI  - Fibril formation from the amyloid-beta peptide is governed by a dynamic
      equilibrium involving association and dissociation of the monomer.
AB  - Here I review the molecular mechanisms by which water-soluble monomeric amyloid
      beta (Abeta) peptides are transformed into well-organized supramolecular
      complexes called amyloid fibrils. The mechanism of amyloid formation is
      considered theoretically on the basis of experimental results, and the structural
      and mechanistic similarities of amyloid fibrils to three-dimensional crystals are
      highlighted. A number of important results from the literature are described.
      These include the observation that a correct ratio of monomer association and
      dissociation rate constants is key for formation of well-organized amyloid
      fibrils. The dynamic nature of the amyloid-beta structure is discussed, along
      with the possibly obligate requirement of the transient formation of a hairpin
      like fold prior to its incorporation into amyloid fibrils. Many rounds of monomer
      association and dissociation events may be present during an apparently silent
      lag-period. Amongst these association/dissociation events, interaction between
      the C-terminal regions of the Abeta peptide seems to be more favored. Such
      association and dissociation events occurring in a "trial-and-error" fashion may
      be an important requirement for the formation of well-organized amyloid fibrils.

PMID- 28510042
TI  - A career in biophysical chemistry beckons: thoughts on the beginning of a journey
      from a young female scientist.

PMID- 28510041
TI  - The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated
      damage in cancers and neurodegenerative diseases.
AB  - The overproduction of reactive oxygen species (ROS) generates oxidative stress in
      cells. Oxidative stress results in various pathophysiological conditions,
      especially cancers and neurodegenerative diseases (NDD). The Keap1-Nrf2 [Kelch
      like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2]
      regulatory pathway plays a central role in protecting cells against oxidative and
      xenobiotic stresses. The Nrf2 transcription factor activates the transcription of
      several cytoprotective genes that have been implicated in protection from cancer
      and NDD. The Keap1-Nrf2 system acts as a double-edged sword: Nrf2 activity
      protects cells and makes the cell resistant to oxidative and electrophilic
      stresses, whereas elevated Nrf2 activity helps in cancer cell survival and
      proliferation. Several groups in the recent past, from both academics and
      industry, have reported the potential role of Nrf2-mediated transcription to
      protect from cancer and NDD, resulting from mechanisms involving xenobiotic and
      oxidative stress. It suggests that the Keap1-Nrf2 system is a potential
      therapeutic target to combat cancer and NDD by designing and developing
      modulators (inhibitors/activators) for Nrf2 activation. Herein, we review and
      discuss the recent advancement in the regulation of the Keap1-Nrf2 system, its
      role under physiological and pathophysiological conditions including cancer and
      NDD, and modulators design strategies for Nrf2 activation.

PMID- 28510044
TI  - A review and summary of the contents of biophysical reviews volume 8, 2016.

PMID- 28510043
TI  - Pseudophosphorylation of cardiac myosin regulatory light chain: a promising new
      tool for treatment of cardiomyopathy.
AB  - Many genetic mutations in sarcomeric proteins, including the cardiac myosin
      regulatory light chain (RLC) encoded by the MYL2 gene, have been implicated in
      familial cardiomyopathies. Yet, the molecular mechanisms by which these mutant
      proteins regulate cardiac muscle mechanics in health and disease remain poorly
      understood. Evidence has been accumulating that RLC phosphorylation has an
      influential role in striated muscle contraction and, in addition to the
      conventional modulation via Ca2+ binding to troponin C, it can regulate cardiac
      muscle function. In this review, we focus on RLC mutations that have been
      reported to cause cardiomyopathy phenotypes via compromised RLC phosphorylation
      and elaborate on pseudo-phosphorylation rescue mechanisms. This new methodology
      has been discussed as an emerging exploratory tool to understand the role of
      phosphorylation as well as a genetic modality to prevent/rescue cardiomyopathy
      phenotypes. Finally, we summarize structural effects post-phosphorylation, a
      phenomenon that leads to an ordered shift in the myosin S1 and RLC conformational
      equilibrium between two distinct states.

PMID- 28510045
TI  - Electrostatic field effects on membrane domain segregation and on lateral
      diffusion.
AB  - Natural membranes are organized structures of neutral and charged molecules
      bearing dipole moments which generate local non-homogeneous electric fields. When
      subjected to such fields, the molecules experience net forces that can modify the
      lipid and protein organization, thus modulating cell activities and influencing
      (or even dominating) the biological functions. The energetics of electrostatic
      interactions in membranes is a long-range effect which can vary over distance
      within r-1 to r-3. In the case of a dipole interacting with a plane of dipoles,
      e.g. a protein interacting with a lipid domain, the interaction is stronger than
      two punctual dipoles and depends on the size of the domain. In this article, we
      review several contributions on how electrostatic interactions in the membrane
      plane can modulate the phase behavior, surface topography and mechanical
      properties in monolayers and bilayers.

PMID- 28510047
TI  - A novel spliceosome-mediated trans-splicing can change our view on genome
      complexity of the divergent eukaryote Giardia intestinalis.
AB  - Although spliceosomal introns are an abundant landmark in eukaryotic genomes, the
      nuclear genome of the divergent eukaryote Giardia intestinalis, the causative
      agent of giardiasis, has been considered as "intron-poor" with only five
      canonical (cis-spliced) introns. However, three research groups (including ours)
      have independently reported a novel class of spliceosomal introns in the G.
      intestinalis genome. Three protein-coding genes are split into pieces in the G.
      intestinalis genome, and each of the partial coding regions was independently
      transcribed into polyadenylated premature mRNAs (pre-mRNAs). The two pre-mRNAs
      directly interact with each other by an intermolecular-stem structure formed
      between their non-coding portions, and are then processed into mature mRNAs by
      spliceosome-mediated trans-splicing. Here, we summarize the recently published
      works on split introns ("splintrons") in the G. intestinalis genome, and then
      provide our speculation on the functional property of the Giardia spliceosomes
      based on the putative ratio of splintrons to canonical introns. Finally, we
      discuss a scenario for the transition from typical GT-AG boundaries to non
      typical AT-AC boundaries in a particular splintron of Giardia.

PMID- 28510046
TI  - Luminescent nanodiamonds for biomedical applications.
AB  - In recent years, nanodiamonds have emerged from primarily an industrial and
      mechanical applications base, to potentially underpinning sophisticated new
      technologies in biomedical and quantum science. Nanodiamonds are relatively
      inexpensive, biocompatible, easy to surface functionalise and optically stable.
      This combination of physical properties are ideally suited to biological
      applications, including intracellular labelling and tracking, extracellular drug
      delivery and adsorptive detection of bioactive molecules. Here we describe some
      of the methods and challenges for processing nanodiamond materials, detection
      schemes and some of the leading applications currently under investigation.

PMID- 28510049
TI  - Education for fathers about newborn screening and leftover dried blood spots.
AB  - The purpose of this research was to assess the impact of an educational
      intervention on paternal knowledge, attitudes, and support about newborn
      screening (NBS) and dried blood spots (DBS). Participants (n = 147) were
      randomized into one of two groups. The results from this study indicated that
      video education tools about NBS and DBS is associated with significantly
      increased knowledge, support, and satisfaction for both NBS and research use of
      DBS and an opt-out consent approach for DBS among fathers.

PMID- 28510048
TI  - nNOS regulation of skeletal muscle fatigue and exercise performance.
AB  - Neuronal nitric oxide synthases (nNOS) are Ca2+/calmodulin-activated enzymes that
      synthesize the gaseous messenger nitric oxide (NO). nNOSMU and the recently
      described nNOSbeta, both spliced nNOS isoforms, are important enzymatic sources
      of NO in skeletal muscle, a tissue long considered to be a paradigmatic system
      for studying NO-dependent redox signaling. nNOS is indispensable for skeletal
      muscle integrity and contractile performance, and deregulation of nNOSMU
      signaling is a common pathogenic feature of many neuromuscular diseases. Recent
      evidence suggests that both nNOSMU and nNOSbeta regulate skeletal muscle size,
      strength, and fatigue resistance, making them important players in exercise
      performance. nNOSMU acts as an activity sensor and appears to assist skeletal
      muscle adaptation to new functional demands, particularly those of endurance
      exercise. Prolonged inactivity leads to nNOS-mediated muscle atrophy through a
      FoxO-dependent pathway. nNOS also plays a role in modulating exercise performance
      in neuromuscular disease. In the mdx mouse model of Duchenne muscular dystrophy,
      defective nNOS signaling is thought to restrict contractile capacity of working
      muscle in two ways: loss of sarcolemmal nNOSMU causes excessive ischemic damage
      while residual cytosolic nNOSMU contributes to hypernitrosylation of the
      ryanodine receptor, causing pathogenic Ca2+ leak. This defect in Ca2+ handling
      promotes muscle damage, weakness, and fatigue. This review addresses these recent
      advances in the understanding of nNOS-dependent redox regulation of skeletal
      muscle function and exercise performance under physiological and neuromuscular
      disease conditions.

PMID- 28510052
TI  - Biophysics to bedside - the transition.

PMID- 28510051
TI  - Proteins in binary solvents.
AB  - Proteins in living organisms exist in complex aqueous solutions or embedded in
      membranes. In solution, proteins are surrounded by a tightly bound hydration
      layer, which is more ordered and less mobile than bulk water. As a consequence,
      water plays a major role in controlling protein structure stability,
      conformational flexibility, dynamics, and functionality, but it also appears that
      protein surface regulates the structuring of the surrounding water. The presence
      of cosolvents can modify the hydration layer characteristics and then the whole
      protein structural and dynamical properties. Because cytoplasm or biological
      liquids are complex solutions, the knowledge of the solvation shell
      characteristics in mixed solvents should be considered as a crucial step in
      describing biological processes at molecular level. This review reports on recent
      studies on the structural and thermodynamic properties of model proteins
      dissolved in binary solvent mixtures by small-angle neutron scattering (SANS) and
      differential scanning microcalorimetry (DSC) techniques. We will show that
      contrast variation SANS experiments allow to acquire a direct knowledge of both
      protein structure and protein solvation shell (in terms of low-resolution shape
      and solvent/cosolvent composition), while DSC experiments provide information on
      all the relevant thermodynamic properties. We will focus on two main points.
      First, an extended description of the thermodynamic model used to define the
      equilibria between water and cosolvent molecules in the protein solvation shell
      will be presented. Second, the determination of the peculiar characteristics of
      the protein solvation layer, which will be illustrated by considering different
      systems. As a conclusion, we will show that the investigation of structure and
      thermodynamics of proteins in binary aqueous mixtures is an important way to
      understand the role of hydration in protein stability and activity.

PMID- 28510050
TI  - A review of multi-domain and flexible molecular chaperones studies by small-angle
      X-ray scattering.
AB  - Intrinsic flexibility is closely related to protein function, and a plethora of
      important regulatory proteins have been found to be flexible, multi-domain or
      even intrinsically disordered. On the one hand, understanding such systems
      depends on how these proteins behave in solution. On the other, small-angle X-ray
      scattering (SAXS) is a technique that fulfills the requirements to study protein
      structure and dynamics relatively quickly with few experimental limitations.
      Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins
      containing flexible and/or disordered regions that play central roles in cellular
      proteostasis. Here, we review the structure and function of these proteins by
      SAXS. Our general approach includes the use of SAXS data to determine size and
      shape parameters, as well as protein shape reconstruction and their validation by
      using accessory biophysical tools. Some remarkable examples are presented that
      exemplify the potential of the SAXS technique. Protein structure can be
      determined in solution even at limiting protein concentrations (for example,
      human mortalin, a mitochondrial Hsp70 chaperone). The protein organization,
      flexibility and function (for example, the J-protein co-chaperones), oligomeric
      status, domain organization, and flexibility (for the Hsp90 chaperone and the Hip
      and Hep1 co-chaperones) may also be determined. Lastly, the shape, structural
      conservation, and protein dynamics (for the Hsp90 chaperone and both p23 and Aha1
      co-chaperones) may be studied by SAXS. We believe this review will enhance the
      application of the SAXS technique to the study of the molecular chaperones.

PMID- 28510055
TI  - Halfway through a 40-year decision: the journey of a medical graduate.

PMID- 28510057
TI  - UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part
      2: selected applications.
AB  - In Part 2 we discuss application of several different types of UV-Vis
      spectroscopy, such as normal, difference, and second-derivative UV absorption
      spectroscopy, fluorescence spectroscopy, linear and circular dichroism
      spectroscopy, and Raman spectroscopy, of the side-chain of tyrosine residues in
      different molecular environments. We review the ways these spectroscopies can be
      used to probe complex protein structures.

PMID- 28510056
TI  - The two sides of a lipid-protein story.
AB  - Protein-membrane interactions play essential roles in a variety of cell functions
      such as signaling, membrane trafficking, and transport. Membrane-recruited
      cytosolic proteins that interact transiently and interfacially with lipid
      bilayers perform several of those functions. Experimental techniques capable of
      probing changes on the structural dynamics of this weak association are
      surprisingly limited. Among such techniques, electron spin resonance (ESR) has
      the enormous advantage of providing valuable local information from both membrane
      and protein perspectives by using intrinsic paramagnetic probes in
      metalloproteins or by attaching nitroxide spin labels to proteins and lipids. In
      this review, we discuss the power of ESR to unravel relevant structural and
      functional details of lipid-peripheral membrane protein interactions with special
      emphasis on local changes of specific regions of the protein and/or the lipids.
      First, we show how ESR can be used to investigate the direct interaction between
      a protein and a particular lipid, illustrating the case of lipid binding into a
      hydrophobic pocket of chlorocatechol 1,2-dioxygenase, a non-heme iron enzyme
      responsible for catabolism of aromatic compounds that are industrially released
      in the environment. In the second case, we show the effects of GPI-anchored
      tissue-nonspecific alkaline phosphatase, a protein that plays a crucial role in
      skeletal mineralization, and on the ordering and dynamics of lipid acyl chains.
      Then, switching to the protein perspective, we analyze the interaction with model
      membranes of the brain fatty acid binding protein, the major actor in the
      reversible binding and transport of hydrophobic ligands such as long-chain,
      saturated, or unsaturated fatty acids. Finally, we conclude by discussing how
      both lipid and protein views can be associated to address a common question
      regarding the molecular mechanism by which dihydroorotate dehydrogenase, an
      essential enzyme for the de novo synthesis of pyrimidine nucleotides, and how it
      fishes out membrane-embedded quinones to perform its function.

PMID- 28510054
TI  - Design and development of genetically encoded fluorescent sensors to monitor
      intracellular chemical and physical parameters.
AB  - Over the past decades many researchers have made major contributions towards the
      development of genetically encoded (GE) fluorescent sensors derived from
      fluorescent proteins. GE sensors are now used to study biological phenomena by
      facilitating the measurement of biochemical behaviors at various scales, ranging
      from single molecules to single cells or even whole animals. Here, we review the
      historical development of GE fluorescent sensors and report on their current
      status. We specifically focus on the development strategies of the GE sensors
      used for measuring pH, ion concentrations (e.g., chloride and calcium), redox
      indicators, membrane potential, temperature, pressure, and molecular crowding. We
      demonstrate that these fluroescent protein-based sensors have a shared history of
      concepts and development strategies, and we highlight the most original concepts
      used to date. We believe that the understanding and application of these various
      concepts will pave the road for the development of future GE sensors and lead to
      new breakthroughs in bioimaging.

PMID- 28510058
TI  - UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part
      1: basic principles and properties of tyrosine chromophore.
AB  - Spectroscopic properties of tyrosine residues may be employed in structural
      studies of proteins. Here we discuss several different types of UV-Vis
      spectroscopy, like normal, difference and second-derivative UV absorption
      spectroscopy, fluorescence spectroscopy, linear and circular dichroism
      spectroscopy, and Raman spectroscopy, and corresponding optical properties of the
      tyrosine chromophore, phenol, which are used to study protein structure.

PMID- 28510059
TI  - Deforestation and Carbon Loss in Southwest Amazonia: Impact of Brazil's Revised
      Forest Code.
AB  - In 2012 Brazil's National Congress altered the country's Forest Code, decreasing
      various environmental protections in the set of regulations governing forests.
      This suggests consequences in increased deforestation and emissions of greenhouse
      gases and in decreased protection of fragile ecosystems. To ascertain the
      effects, a simulation was run to the year 2025 for the municipality (county) of
      Boca do Acre, Amazonas state, Brazil. A baseline scenario considered historical
      behavior (which did not respect the Forest Code), while two scenarios considered
      full compliance with the old Forest Code (Law 4771/1965) and the current Code
      (Law 12,651/2012) regarding the protection of "areas of permanent preservation"
      (APPs) along the edges of watercourses. The models were parameterized from
      satellite imagery and simulated using Dinamica-EGO software. Deforestation actors
      and processes in the municipality were observed in loco in 2012. Carbon emissions
      and loss of forest by 2025 were computed in the three simulation scenarios. There
      was a 10% difference in the loss of carbon stock and of forest between the
      scenarios with the two versions of the Forest Code. The baseline scenario showed
      the highest loss of carbon stocks and the highest increase in annual emissions.
      The greatest damage was caused by not protecting wetlands and riparian zones.

PMID- 28510060
TI  - The role of protein kinase C-mediated phosphorylation of sarcomeric proteins in
      the heart-detrimental or beneficial?
AB  - Protein kinase C (PKC) is a family of serine/threonine protein kinases, and
      alterations have been found in PKC isoform expression and localization in the
      failing heart. These alterations in PKC activation levels influence the PKC
      mediated phosphorylation status of cellular target proteins involved in Ca2+
      handling and sarcomeric contraction. The differences observed in the effects due
      to PKC-mediated phosphorylation may underlie part of the contractile dysfunction
      observed in the failing heart. It is therefore important to establish the
      beneficial and detrimental effects of this kinase in the healthy and failing
      heart. The function of PKC has been studied intensively; however, the complexity
      of the regulation of this kinase makes the interpretation of the different
      effects difficult. The main focus of this review is the (patho)physiological
      impact of phosphorylation of sarcomeric proteins, myosin light chain-2, troponin
      I and T, desmin, myosin binding protein-C, and titin by PKC.

PMID- 28510061
TI  - Measuring the flow of molecules in cells.
AB  - No methods proposed thus far have the capability to measure molecular flow in
      live cells at the single molecule level. Here, we review the potentiality of a
      newly established method based on the spatial correlation of fluorescence
      fluctuations at a pair of points in the sample (pair correlation method). The
      pair correlation function (pCF) offers a unique tool to probe the directionality
      of intracellular traffic, by measuring the accessibility of the cellular
      landscape and its role in determining the diffusive routes adopted by molecules.
      The sensitivity of the pCF method toward detection of barriers means that
      different structural elements of the cell can be tested in terms of penetrability
      and mechanisms of regulation imparted on molecular flow. This has been recently
      demonstrated in a series of studies looking at molecular transport inside live
      cells. Here, we will review the theory behind detection of barriers to molecular
      flow, the rules to interpret pCF data, and relevant applications to intracellular
      transport.

PMID- 28510062
TI  - Biological applications of second harmonic imaging.
AB  - Second Harmonic Generation (SHG) microscopy dates back to 1974, but effective
      biological use of the technique has a history of barely 10 years. It is now
      widely used to image collagen in many different applications, and is becoming
      useful for imaging myosin and some polysaccharides. A separate line on research
      has focussed on SHG dyes, which can provide high-speed indication of membrane
      potential and are now in use in neurobiology. This review looks at the progress
      to date in these different fields.

PMID- 28510063
TI  - Structural gymnastics of multifunctional metamorphic proteins.
AB  - The classic structure-function paradigm holds that a protein exhibits a single
      well-defined native state that gives rise to its biological function.
      Nonetheless, over the past few decades, numerous examples of proteins exhibiting
      biological function arising from multiple structural states of varying disorder
      have been identified. Most recently, several examples of 'metamorphic proteins',
      able to interconvert between vastly different native-like topologies under
      physiological conditions, have been characterised with multiple functions. In
      this review, we look at the concept of protein metamorphosis in relation to the
      current understanding of the protein structure-function landscape. Although
      structural dynamism observed for metamorphic proteins provides a novel source of
      functional versatility, the dynamic nature of the metamorphic proteins generally
      makes them difficult to identify and probe using conventional protein structure
      determination methods. However, as the existence of metamorphic proteins has now
      been established and techniques enabling the analysis of multiple protein
      conformers are improving, it is likely that this class will continue to grow in
      number.

PMID- 28510065
TI  - Biophysical educational experiment: science and goodwill in Latin America and
      Africa.

PMID- 28510064
TI  - Optical coherence tomography: fundamental principles, instrumental designs and
      biomedical applications.
AB  - The advances made in the last two decades in interference technologies, optical
      instrumentation, catheter technology, optical detectors, speed of data
      acquisition and processing as well as light sources have facilitated the
      transformation of optical coherence tomography from an optical method used mainly
      in research laboratories into a valuable tool applied in various areas of
      medicine and health sciences. This review paper highlights the place occupied by
      optical coherence tomography in relation to other imaging methods that are used
      in medical and life science areas such as ophthalmology, cardiology, dentistry
      and gastrointestinal endoscopy. Together with the basic principles that lay
      behind the imaging method itself, this review provides a summary of the
      functional differences between time-domain, spectral-domain and full-field
      optical coherence tomography, a presentation of specific methods for processing
      the data acquired by these systems, an introduction to the noise sources that
      plague the detected signal and the progress made in optical coherence tomography
      catheter technology over the last decade.

PMID- 28510066
TI  - The Delta Opioid Receptor in Pain Control.
AB  - Nowadays, the delta opioid receptor (DOPr) represents a promising target for the
      treatment of chronic pain and emotional disorders. Despite the fact that they
      produce limited antinociceptive effects in healthy animals and in most acute pain
      models, DOPr agonists have shown efficacy in various chronic pain models. In this
      chapter, we review the progresses that have been made over the last decades in
      understanding the role played by DOPr in the control of pain. More specifically,
      the distribution of DOPr within the central nervous system and along pain
      pathways is presented. We also summarize the literature supporting a role for
      DOPr in acute, tonic, and chronic pain models, as well as the mechanisms
      regulating its activity under specific conditions. Finally, novel compounds that
      have make their way to clinical trials are discussed.

PMID- 28510068
TI  - New direct dynamic models of protein interactions coupled to photosynthetic
      electron transport reactions.
AB  - This review covers the methods of computer simulation of protein interactions
      taking part in photosynthetic electron transport reactions. A direct
      multiparticle simulation method that simulates reactions describing interactions
      of ensembles of molecules in the heterogeneous interior of a cell is developed.
      In the models, protein molecules move according to the laws of Brownian dynamics,
      mutually orient themselves in the electrical field, and form complexes in the 3D
      scene. The method allows us to visualize the processes of molecule interactions
      and to calculate the rate constants for protein complex formation reactions in
      the solution and in the photosynthetic membrane. Three-dimensional multiparticle
      computer models for simulating the complex formation kinetics for plastocyanin
      with photosystem I and cytochrome bf complex, and ferredoxin with photosystem I
      and ferredoxin:NADP+-reductase are considered. Effects of ionic strength are
      featured for wild type and mutant proteins. The computer multiparticle models
      describe nonmonotonic dependences of complex formation rates on the ionic
      strength as the result of long-range electrostatic interactions.

PMID- 28510067
TI  - Immunization During Pregnancy: Impact on the Infant.
AB  - Maternal immunization has undergone a paradigm shift in recent years, as women
      and healthcare providers accept and recognize the benefits of this strategy not
      only for the pregnant woman but also for the developing fetus and young infant.
      This article reviews the evidence for active immunization during pregnancy, with
      an emphasis on perinatal and infant outcomes. Current recommendations for
      immunization during pregnancy are presented, with particular focus on the
      routinely recommended vaccines during pregnancy: influenza and Tdap (tetanus,
      diphtheria, and pertussis). We discuss future research directions, maternal
      vaccines in development, and considerations for optimizing and advancing this
      underutilized strategy.

PMID- 28510071
TI  - Surgical techniques for open fetal repair of myelomeningocele.
AB  - The current standard for fetal repair of myelomeningocele is an open exposure of
      the gravid uterus with control of the amniotic membranes, and then a multi-layer
      closure of the fetal defect. The nature of the surgical repair has evolved and
      requires a series of steps that take into account the delicate nature of the
      fetal tissues. The individual surgical steps are described including potential
      pitfalls.

PMID- 28510070
TI  - Sonographic detection of open spina bifida in the first trimester: review of the
      literature.
AB  - In the beginnings, sonographic diagnosis of open spina bifida (OSB) relied on the
      meticulous scanning of the fetal vertebrae for abnormalities but many defects
      were missed. After the mid-1980s, however, with the description of the
      intracranial findings in the second trimester (the "lemon sign" and the "banana
      sign"), the prenatal diagnosis of OSB was enhanced. In the last 2 decades, there
      has been widespread uptake of routine ultrasound examination in the first
      trimester of pregnancy with the purpose of the measurement of fetal crown-rump
      length to determine gestational age, to screen for trisomy 21 and other
      aneuploidies, mainly with the nuchal translucency, and for diagnosis of many
      major abnormalities. Many papers were published focusing on early diagnosis of
      myelomeningocele (MMC), and the objective of this review is to summarize the
      different techniques described regarding prenatal diagnosis of OSB in the first
      trimester of pregnancy.

PMID- 28510069
TI  - Multi-dimensional correlative imaging of subcellular events: combining the
      strengths of light and electron microscopy.
AB  - To genuinely understand how complex biological structures function, we must
      integrate knowledge of their dynamic behavior and of their molecular machinery.
      The combined use of light or laser microscopy and electron microscopy has become
      increasingly important to our understanding of the structure and function of
      cells and tissues at the molecular level. Such a combination of two or more
      different microscopy techniques, preferably with different spatial- and temporal
      resolution limits, is often referred to as 'correlative microscopy'. Correlative
      imaging allows researchers to gain additional novel structure-function
      information, and such information provides a greater degree of confidence about
      the structures of interest because observations from one method can be compared
      to those from the other method(s). This is the strength of correlative (or
      'combined') microscopy, especially when it is combined with combinatorial or non
      combinatorial labeling approaches. In this topical review, we provide a brief
      historical perspective of correlative microscopy and an in-depth overview of
      correlative sample-preparation and imaging methods presently available, including
      future perspectives on the trend towards integrative microscopy and
      microanalysis.

PMID- 28510072
TI  - Fetal ventriculomegaly: Diagnosis, treatment, and future directions.
AB  - Fetal ventriculomegaly (VM) refers to the enlargement of the cerebral ventricles
      in utero. It is associated with the postnatal diagnosis of hydrocephalus. VM is
      clinically diagnosed on ultrasound and is defined as an atrial diameter greater
      than 10 mm. Because of the anatomic detailed seen with advanced imaging, VM is
      often further characterized by fetal magnetic resonance imaging (MRI). Fetal VM
      is a heterogeneous condition with various etiologies and a wide range of
      neurodevelopmental outcomes. These outcomes are heavily dependent on the presence
      or absence of associated anomalies and the direct cause of the ventriculomegaly
      rather than on the absolute degree of VM. In this review article, we discuss
      diagnosis, work-up, counseling, and management strategies as they relate to fetal
      VM. We then describe imaging-based research efforts aimed at using prenatal data
      to predict postnatal outcome. Finally, we review the early experience with fetal
      therapy such as in utero shunting, as well as the advances in prenatal diagnosis
      and fetal surgery that may begin to address the limitations of previous
      therapeutic efforts.

PMID- 28510075
TI  - Editorial.

PMID- 28510074
TI  - Contractility assessment in enzymatically isolated cardiomyocytes.
AB  - The use of enzymatically isolated cardiac myocytes is ubiquitous in modern
      cardiovascular research. Parallels established between cardiomyocyte shortening
      responses and those of intact tissue make the cardiomyocyte an invaluable
      experimental model of cardiac function. Much of our understanding regarding the
      fundamental processes underlying heart function is owed to our increasing
      capabilities in single-cell stimulation and direct or indirect observation, as
      well as quantitative analysis of such cells. Of the many important mechanisms and
      functions that can be readily assessed in cardiomyocytes at all stages of
      development, contractility is the most representative and one of the most
      revealing. The purpose of this review is to provide a survey of various
      methodological approaches in the literature used to assess adult and neonatal
      cardiomyocyte contractility. The various methods employed to evaluate the
      contractile behavior of enzymatically isolated mammalian cardiac myocytes can be
      conveniently divided into two general categories-those employing optical (image)
      based systems and those that use transducer-based technologies. This survey is by
      no means complete, but we have made an effort to include the most popular methods
      in terms of reliability and accessibility. These techniques are in constant
      evolution and hold great promise for the next generation of breakthrough studies
      in cell biology for the prevention, treatment, and cure of cardiovascular
      diseases.

PMID- 28510076
TI  - Application of a systems approach to study developmental gene regulation.
AB  - All cells in a multicellular organism contain the same genome, yet different cell
      types express different sets of genes. Recent advances in high throughput genomic
      technologies have opened up new opportunities to understand the gene regulatory
      network in diverse cell types in a genome-wide manner. Here, I discuss recent
      advances in experimental and computational approaches for the study of gene
      regulation in embryonic development from a systems perspective. This review is
      written for computational biologists who have an interest in studying
      developmental gene regulation through integrative analysis of gene expression,
      chromatin landscape, and signaling pathways. I highlight the utility of publicly
      available data and tools, as well as some common analysis approaches.

PMID- 28510073
TI  - Modeling of mammalian olfactory receptors and docking of odorants.
AB  - Olfactory receptors (ORs) belong to the superfamily of G protein-coupled
      receptors (GPCRs), the second largest class of genes after those related to
      immunity, and account for about 3 % of mammalian genomes. ORs are present in all
      multicellular organisms and represent more than half the GPCRs in mammalian
      species (e.g., the mouse OR repertoire contains >1,000 functional genes). ORs are
      mainly expressed in the olfactory epithelium where they detect odorant molecules,
      but they are also expressed in a number of other cells, such as sperm cells,
      although their functions in these cells remain mostly unknown. It has recently
      been reported that ORs are present in tumoral tissues where they are expressed at
      different levels than in healthy tissues. A specific OR is over-expressed in
      prostate cancer cells, and activation of this OR has been shown to inhibit the
      proliferation of these cells. Odorant stimulation of some of these receptors
      results in inhibition of cell proliferation. Even though their biological role
      has not yet been elucidated, these receptors might constitute new targets for
      diagnosis and therapeutics. It is important to understand the activation
      mechanism of these receptors at the molecular level, in particular to be able to
      predict which ligands are likely to activate a particular receptor
      ('deorphanization') or to design antagonists for a given receptor. In this
      review, we describe the in silico methodologies used to model the three
      dimensional (3D) structure of ORs (in the more general framework of GPCR
      modeling) and to dock ligands into these 3D structures.

PMID- 28510077
TI  - Molecular dynamics simulations of membrane proteins.
AB  - Membrane proteins control the traffic across cell membranes and thereby play an
      essential role in cell function from transport of various solutes to immune
      response via molecular recognition. Because it is very difficult to determine the
      structures of membrane proteins experimentally, computational methods have been
      increasingly used to study their structure and function. Here we focus on two
      classes of membrane proteins-ion channels and transporters-which are responsible
      for the generation of action potentials in nerves, muscles, and other excitable
      cells. We describe how computational methods have been used to construct models
      for these proteins and to study the transport mechanism. The main computational
      tool is the molecular dynamics (MD) simulation, which can be used for everything
      from refinement of protein structures to free energy calculations of transport
      processes. We illustrate with specific examples from gramicidin and potassium
      channels and aspartate transporters how the function of these membrane proteins
      can be investigated using MD simulations.

PMID- 28510079
TI  - Conformational flexibility of N-glycans in solution studied by REMD simulations.
AB  - Protein-glycan recognition regulates a wide range of biological and pathogenic
      processes. Conformational diversity of glycans in solution is apparently
      incompatible with specific binding to their receptor proteins. One possibility is
      that among the different conformational states of a glycan, only one conformer is
      utilized for specific binding to a protein. However, the labile nature of glycans
      makes characterizing their conformational states a challenging issue. All-atom
      molecular dynamics (MD) simulations provide the atomic details of glycan
      structures in solution, but fairly extensive sampling is required for simulating
      the transitions between rotameric states. This difficulty limits application of
      conventional MD simulations to small fragments like di- and tri-saccharides.
      Replica-exchange molecular dynamics (REMD) simulation, with extensive sampling of
      structures in solution, provides a valuable way to identify a family of glycan
      conformers. This article reviews recent REMD simulations of glycans carried out
      by us or other research groups and provides new insights into the conformational
      equilibria of N-glycans and their alteration by chemical modification. We also
      emphasize the importance of statistical averaging over the multiple conformers of
      glycans for comparing simulation results with experimental observables. The
      results support the concept of "conformer selection" in protein-glycan
      recognition.

PMID- 28510081
TI  - QT Prolongation as an Isolated Long-Term Cardiac Manifestation of Dichlorvos
      Organophosphate Poisoning in Rats.
AB  - Organophosphates (OP) are used extensively as pesticides and as chemical weapons.
      Cardiotoxicity is a major concern in survivors of the acute poisoning. To
      characterize the delayed cardiac effects of OP, rats were poisoned by
      intraperitoneal administration of dichlorvos. In group I, poisoning (0.25-, 0.75
      , 1.4-LD50) was followed by application of atropine and obidoxime. In group II,
      poisoning (0.35-, 0.5-LD50) was done without antidotes. Cardiac evaluation
      included electrocardiography and echocardiography 2- and 6-week post-exposure,
      arrhythmia susceptibility following administration of Isoproterenol (150 mcg/kg),
      and histological evaluation. All poisoned animals displayed cholinergic symptoms.
      In group I, all animals exposed to 1.4-LD50 (n = 3) had profound convulsions and
      died despite antidote treatment. However, in the lower doses, all animals
      survived and no cardiac abnormalities were noted during follow-up. In group II,
      six animals had convulsions and died. Surviving animals had mild but significant
      prolongation of corrected QT at both 2 and 6 weeks, compared to shams. There were
      no notable echocardiographic, gravimetric, or histological differences between
      poisoned and sham animals. Our data indicate that dichlorvos poisoning is
      associated with QT prolongation without anatomical or histopathological
      abnormalities. This new model can be used to elaborate the molecular mechanism?s
      of QT prolongation following OP poisoning.

PMID- 28510078
TI  - Assessing and refining molecular dynamics simulations of proteins with nuclear
      magnetic resonance data.
AB  - The sophistication of the force fields, algorithms and hardware used for
      molecular dynamics (MD) simulations of proteins is continuously increasing. No
      matter how advanced the methodology, however, it is essential to evaluate the
      appropriateness of the structures sampled in a simulation by comparison with
      quantitative experimental data. Solution nuclear magnetic resonance (NMR) data
      are particularly useful for checking the quality of protein simulations, as they
      provide both structural and dynamic information on a variety of temporal and
      spatial scales. Here, various features and implications of using NMR data to
      validate and bias MD simulations are outlined, including an overview of the
      different types of NMR data that report directly on structural properties and of
      relevant simulation techniques. The focus throughout is on how to properly
      account for conformational averaging, particularly within the context of the
      assumptions inherent in the relationships that link NMR data to structural
      properties.

PMID- 28510080
TI  - Identifying and Prioritizing the Barriers and Facilitators to the Self-Management
      of Type 2 Diabetes Mellitus: A Community-Centered Approach.
AB  - OBJECTIVE: Self-management of type 2 diabetes mellitus is crucial to controlling
      the disease and preventing harm. Multiple factors have been identified in the
      literature as potential barriers and facilitators to self-management, but the
      magnitude and directionality of these factors are seldom studied. We sought to
      develop and test an instrument to identify and quantify the barriers and
      facilitators to self-management of type 2 diabetes. METHODS: A community-centered
      approach was used to design, implement, and interpret the results of a stated
      preference study. All activities were guided by a diverse stakeholder board.
      Based on previously reported development work, a novel survey instrument
      consisting of 13 potential barriers and facilitators was pretested and piloted in
      our local community. Participants were asked to discuss, rate, and rank each
      factor. A simple self-explicated method was used to quantify the data and Z
      scores were used for hypothesis testing. RESULTS: In total, 25 patients with self
      reported type 2 diabetes (64% female; 92% minorities) participated in the pretest
      and pilot. Time commitments (Z = -3.72), lack of active support groups (Z = 
      3.39) and other resources in the local community (Z = -2.96), and
      language/culture (Z = -2.69) were identified as barriers to self-management.
      Access to healthy food (Z = +5.68), personal understanding (Z = +4.81), and
      communication with healthcare providers (Z = +4.62) were identified as
      facilitators. CONCLUSION: We demonstrate that factors impacting self-management
      can be quantified and categorized as barriers and facilitators. While further
      refinement to some factors and investigation into alternative prioritization
      methods is necessary, our stakeholder board endorsed moving this to a large
      nationally representative study to see how these factors vary across different
      people.

PMID- 28510084
TI  - Innovations in publication: free sharing of all Biophysical Reviews' content.

PMID- 28510082
TI  - Biomedical applications of nanotechnology.
AB  - The ability to investigate substances at the molecular level has boosted the
      search for materials with outstanding properties for use in medicine. The
      application of these novel materials has generated the new research field of
      nanobiotechnology, which plays a central role in disease diagnosis, drug design
      and delivery, and implants. In this review, we provide an overview of the use of
      metallic and metal oxide nanoparticles, carbon-nanotubes, liposomes, and
      nanopatterned flat surfaces for specific biomedical applications. The chemical
      and physical properties of the surface of these materials allow their use in
      diagnosis, biosensing and bioimaging devices, drug delivery systems, and bone
      substitute implants. The toxicology of these particles is also discussed in the
      light of a new field referred to as nanotoxicology that studies the surface
      effects emerging from nanostructured materials.

PMID- 28510086
TI  - New insights into real-time multiprotein fluorescence microscopy.

PMID- 28510087
TI  - Why we need to stop explaining science.

PMID- 28510085
TI  - Cardiac aging and heart disease in humans.
AB  - The world population continues to grow older rapidly, mostly because of declining
      fertility and increasing longevity. Since age represents the largest risk factor
      for cardiovascular disease, the prevalence of these pathologies increases
      dramatically with increasing age. In order to improve patient care and prevention
      for age-related cardiac diseases, insight should be gained from the analysis of
      processes involved in and leading to cardiac aging. It is from this perspective
      that we provide here an overview of changes associated with age in the heart on
      four levels: functional, structural, cellular and molecular. We highlight those
      changes that are in common with the development of the two major age-associated
      cardiac pathologies: heart failure and atrial fibrillation. These commonly
      affected processes in aging and cardiac pathophysiology may provide an
      explanation for the age risk factor in cardiac disease.

PMID- 28510083
TI  - Software for molecular docking: a review.
AB  - Molecular docking methodology explores the behavior of small molecules in the
      binding site of a target protein. As more protein structures are determined
      experimentally using X-ray crystallography or nuclear magnetic resonance (NMR)
      spectroscopy, molecular docking is increasingly used as a tool in drug discovery.
      Docking against homology-modeled targets also becomes possible for proteins whose
      structures are not known. With the docking strategies, the druggability of the
      compounds and their specificity against a particular target can be calculated for
      further lead optimization processes. Molecular docking programs perform a search
      algorithm in which the conformation of the ligand is evaluated recursively until
      the convergence to the minimum energy is reached. Finally, an affinity scoring
      function, DeltaG [U total in kcal/mol], is employed to rank the candidate poses
      as the sum of the electrostatic and van der Waals energies. The driving forces
      for these specific interactions in biological systems aim toward
      complementarities between the shape and electrostatics of the binding site
      surfaces and the ligand or substrate.

PMID- 28510088
TI  - Seeing the light with BLUF proteins.
AB  - First described about 15 years ago, BLUF (Blue Light Using Flavin) domains are
      light-triggered switches that control enzyme activity or gene expression in
      response to blue light, remaining activated for seconds or even minutes after
      stimulation. The conserved, ferredoxin-like fold holds a flavin chromophore that
      captures the light and somehow triggers downstream events. BLUF proteins are
      found in both prokaryotes and eukaryotes and have a variety of architectures and
      oligomeric forms, but the BLUF domain itself seems to have a well-preserved
      structure and mechanism that have been the focus of intense study for a number of
      years. Crystallographic and NMR structures of BLUF domains have been solved, but
      the conflicting models have led to considerable debate about the atomic details
      of photo-activation. Advanced spectroscopic and computational methods have been
      used to analyse the early events after photon absorption, but these too have led
      to widely differing conclusions. New structural models are improving our
      understanding of the details of the mechanism and may lead to novel tailor-made
      tools for optogenetics.

PMID- 28510091
TI  - The emergence of multiple particle tracking in intracellular trafficking of
      nanomedicines.
AB  - A growing number of nanoparticle systems, termed "nanomedicines", are being
      developed for diagnostic and therapeutic applications. Nanoparticles can employ
      various cellular entry pathways and trafficking mechanisms to effectively deliver
      drugs, biomolecules, and imaging agents to precise sub-cellular locations.
      However, the dynamic transport of nanoparticles through the complex intracellular
      environment is not well understood, having been primarily studied with static or
      bulk averaged methods in the past. Such techniques do not provide detailed
      information regarding the transport mechanism and rates of individual
      nanoparticles, where understanding of the interaction of nanoparticles with the
      cellular environment remains incomplete. Recent advances in live-cell
      fluorescence microscopy and real-time multiple particle tracking (MPT) have
      facilitated an improved understanding of cell trafficking pathways. Understanding
      the dynamic transport of nanoparticles as they are delivered into complex
      cellular components may lead to rational improvements in the design of
      nanomedicines. This review discusses different cellular uptake and trafficking
      pathways of nanomedicines, briefly highlights current fluorescence microscopy
      tools, and provides examples from the recent literature on the use of MPT and its
      applications.

PMID- 28510092
TI  - Protein sorting and membrane-mediated interactions.
AB  - Sorting of membrane proteins is of vital importance for living cells. Indeed,
      roughly one-third of a eukaryotic cell's proteome consists of peripheral and
      transmembrane proteins. These need to be properly distributed and dynamically
      maintained at distinct locations in the compartmentalized cell, and one may
      wonder how proteins determine where, when, and how to travel to reach a specific
      organelle. While specific binary interactions between proteins have been invoked
      in explaining the trafficking and sorting processes, a more active role of lipids
      in this context has become visible in recent years. In particular, membrane
      mediated interactions have been suggested to serve as a robust physicochemical
      mechanism to facilitate protein sorting. Here, we will review some recent
      insights into these aspects.

PMID- 28510095
TI  - The relationship between postmenopausal women's sclerostin levels and their bone
      density, age, body mass index, hormonal status, and smoking and consumption of
      coffee and dairy products.

PMID- 28510094
TI  - The use of biophysical proteomic techniques in advancing our understanding of
      diseases.
AB  - The use of proteomic approaches in investigating diseases is continuing to expand
      and has started to provide answers to substantial gaps in our understanding of
      disease pathogenesis as well as in the development of effective strategies for
      the early diagnosis and treatment of diseases. Biophysical techniques form a
      crucial part of the advanced proteomic techniques currently used and include mass
      spectrometry and protein separation techniques, such as two-dimensional gel
      electrophoresis and liquid chromatography. The application of biophysical
      proteomic techniques in the study of disease includes delineation of altered
      protein expression, not only at the whole-cell or tissue levels, but also in
      subcellular structures, protein complexes, and biological fluids. These
      techniques are also being used for the discovery of novel disease biomarkers,
      exploration of the pathogenesis of diseases, development of new diagnostic
      methodologies, and identification of new targets for therapeutics. Proteomic
      techniques also have the potential for accelerating drug development through more
      effective strategies for evaluating a specific drug's therapeutic effects and
      toxicity. This article discusses the application of biophysical proteomic
      techniques in delineating cardiovascular disease and other diseases, as well as
      the limitations and future research directions required for these techniques to
      gain greater acceptance and have a larger impact.

PMID- 28510090
TI  - The melatonin immunomodulatory actions in radiotherapy.
AB  - Radiotherapy has a key role in cancer treatment in more than half of patients
      with cancer. The management of severe side effects of this treatment modality is
      a limiting factor to appropriate treatment. Immune system responses play a
      pivotal role in many of the early and late side effects of radiation. Moreover,
      immune cells have a significant role in tumor response to radiotherapy, such as
      angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown
      appropriate immune regulatory properties that may ameliorate toxicity induced by
      radiation in various organs. These effects are mediated through various
      modulatory effects of melatonin in different levels of tissue reaction to
      ionizing radiation. The effects on the DNA repair system, antioxidant enzymes,
      immune cells, cytokines secretion, transcription factors, and protein kinases are
      most important. Moreover, anti-cancer properties of melatonin may increase the
      therapeutic ratio of radiotherapy. Clinical applications of this agent for the
      management of malignancies such as breast cancer have shown promising results. It
      seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of
      some immune cell responses are the main anti-tumor effects of melatonin that may
      help to improve response of the tumor to radiotherapy. In this review, the
      effects of melatonin on the modulation of immune responses in both normal and
      tumor tissues will be discussed.

PMID- 28510093
TI  - Toward a molecular understanding of nanoparticle-protein interactions.
AB  - Wherever nanoparticles (NPs) come in contact with a living organism, physical and
      chemical interactions take place between the surfaces of the NPs and biomatter,
      in particular proteins. When NP are exposed to biological fluids, an adsorption
      layer of proteins, a "protein corona" forms around the NPs. Consequently, living
      systems interact with the protein-coated NP rather than with a bare NP. To
      anticipate biological responses to NPs, we thus require comprehensive knowledge
      of the interactions at the bio-nano interface. In recent years, a wide variety of
      biophysical techniques have been employed to elucidate mechanistic aspects of NP
      protein interactions. In this brief review, we present the latest findings
      regarding the composition of the protein corona as it forms on NPs in the blood
      stream. We also discuss molecular aspects of this adsorption layer and its time
      evolution. The current state of knowledge is summarized, and issues that still
      need to be addressed to further advance our understanding of NP-protein
      interactions are identified.

PMID- 28510096
TI  - Birth weight and its relation with medical nutrition therapy in gestational
      diabetes.
AB  - PURPOSE: The cornerstone in treatment of gestational diabetes mellitus (GDM) is
      medical nutrition therapy (MNT), but the effect on birth weight is disputed. The
      birth weight was evaluated with respect to length of MNT and adherence to diet.
      METHODS: We performed a cohort study on 436 women with GDM and 254 non-diabetic
      women. Women with a normal oral glucose tolerance test were included as controls
      as they had similar background predisposition as the women with GDM. The GDM
      women were subdivided according to MNT and the nutritional status was further
      stratified according to adherence to the current dietary guidelines. RESULTS:
      Birth weight above 4 kg was more prevalent in the non-diabetic women compared to
      the diet-treated GDM women (27 vs. 18%, p = 0.012) but similar to the GDM women
      who had no MNT (24%). Lower birth weight was associated with longer duration of
      MNT (r = -0.13, p = 0.021). The birth weight was 1.2 g lower per day of
      treatment. CONCLUSIONS: Medical nutrition therapy was associated with reduction
      of the fetal weight in women with GDM and the weight decreases with length of
      treatment. Birth weight above 4 kg was as prominent in the non-diabetic women as
      in the women with GDM without MNT.

PMID- 28510089
TI  - Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer,
      antimicrobial and immunosuppressive agents.
AB  - Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen
      to induce oxidative stress that can be used to kill pathogens, cancer cells and
      other highly proliferative cells. There is a growing number of clinically
      approved photosensitisers and applications of PDT, whose main advantages include
      the possibility of selective targeting, localised action and stimulation of the
      immune responses. Further improvements and broader use of PDT could be
      accomplished by designing new photosensitisers with increased selectivity and
      bioavailability. Porphyrin-based photosensitisers with amphiphilic properties,
      bearing one or more positive charges, are an effective tool in PDT against
      cancers, microbial infections and, most recently, autoimmune skin disorders. The
      aim of the review is to present some of the recent examples of the applications
      and research that employ this specific group of photosensitisers. Furthermore, we
      will highlight the link between their structural characteristics and PDT
      efficiency, which will be helpful as guidelines for rational design and
      evaluation of new PSs.

PMID- 28510097
TI  - AGO Austria recommendation on screening and diagnosis of Lynch syndrome (LS).
AB  - PURPOSE: This manuscript reports the consensus recommendations on screening and
      diagnosis of Lynch syndrome (LS) in patients with endometrial or ovarian cancer
      as well as on possible preventive measures in effectively LS-diagnosed women. The
      recommendations are issued by the Austrian Arbeitsgemeinschaft fur Gynakologische
      Onkologie (AGO) of the Osterreichischen Gesellschaft fur Gynakologie und
      Geburtshilfe (OEGGG) after consultation of the most recent and relevant
      literature and following deliberation by the Genetic Task-Force convoked May,
      2015 by the AGO Council. RESULTS AND CONCLUSION: The Austrian AGO recommends
      immunohistochemical tissue screening for type-I and type-II endometrial cancers
      in all patients below the age of 70 years, and for all endometrioid and clear
      cell ovarian cancers independently of the patient's age. If needed
      immunohistochemistry should be complemented by tissue MLH1 promotor
      hypermethylation testing and/or microsatellite instability (MSI) analysis. The
      diagnosis LS requires confirmation through identification of a germline mutation
      by a molecular genetic examination in the mismatch repair genes using the
      patient's blood. This should be performed without preceding tissue screening when
      in LS-associated cancer patients the family history fulfills the Amsterdam II or
      the revised Bethesda criteria. In LS-diagnosed women, the age for prophylactic
      surgery should be set flexibly based on an informed consent. Regarding the
      monitoring of these women, chemo-preventive measures as well as screening
      procedures either to avoid or to early detect LS-related tumors are discussed
      with a special light on their specific limitations.

PMID- 28510100
TI  - Liposomal systems as carriers for bioactive compounds.
AB  - Since the revolutionary discovery that phospholipids can form closed bilayered
      structures in aqueous systems, the study of liposomes has become a very
      interesting area of research. The versatility and amazing biocompatibility of
      liposomes has resulted in their wide-spread use in many scientific fields, and
      many of their applications, especially in medicine, have yielded breakthroughs in
      recent decades. Specifically, their easy preparation and various structural
      aspects have given rise to broadly usable methodologies to internalize different
      compounds, with either lipophilic or hydrophilic properties. The study of
      compounds with potential biotechnological application(s) is generally related to
      evaluation and risk assessment of the possible cytotoxic or therapeutic effects
      of the compound under study. In most cases, undesirable side-effects are
      associated with an interaction of the liposome with the cell membrane and/or its
      absorption and subsequent interaction with a cellular biomolecule. Liposomal
      carrier systems have an unprecedented potential for delivering bioactive
      substances to specific molecular targets due to their biocompatibility,
      biodegradability and low toxicity. Liposomes are therefore considered to be an
      invaluable asset in applied biotechnology studies due to their potential for
      interaction with both hydrophilic and lipophilic compounds.

PMID- 28510099
TI  - Biophysical chemistry of the ageing eye lens.
AB  - This review examines both recent and historical literature related to the
      biophysical chemistry of the proteins in the ageing eye, with a particular focus
      on cataract development. The lens is a vital component of the eye, acting as an
      optical focusing device to form clear images on the retina. The lens maintains
      the necessary high transparency and refractive index by expressing crystallin
      proteins in high concentration and eliminating all large cellular structures that
      may cause light scattering. This has the consequence of eliminating lens fibre
      cell metabolism and results in mature lens fibre cells having no mechanism for
      protein expression and a complete absence of protein recycling or turnover. As a
      result, the crystallins are some of the oldest proteins in the human body. Lack
      of protein repair or recycling means the lens tends to accumulate damage with age
      in the form of protein post-translational modifications. The crystallins can be
      subject to a wide range of age-related changes, including isomerisation,
      deamidation and racemisation. Many of these modification are highly correlated
      with cataract formation and represent a biochemical mechanism for age-related
      blindness.

PMID- 28510098
TI  - Body mass index and risk of colorectal carcinoma subtypes classified by tumor
      differentiation status.
AB  - Previous studies suggest that abnormal energy balance status may dysregulate
      intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet
      little is known about how host energy balance and obesity influence enterocyte
      differentiation during carcinogenesis. We hypothesized that the association
      between high body mass index (BMI) and colorectal carcinoma incidence might
      differ according to tumor histopathologic differentiation status. Using databases
      of the Nurses' Health Study and Health Professionals Follow-up Study, and
      duplication-method Cox proportional hazards models, we prospectively examined an
      association between BMI and the incidence of colorectal carcinoma subtypes
      classified by differentiation features. 120,813 participants were followed for 26
      or 32 years and 1528 rectal and colon cancer cases with available tumor
      pathological data were documented. The association between BMI and colorectal
      cancer risk significantly differed depending on the presence or absence of poorly
      differentiated foci (Pheterogeneity = 0.006). Higher BMI was associated with a
      higher risk of colorectal carcinoma without poorly-differentiated foci (>=30.0
      vs. 18.5-22.4 kg/m2: multivariable-adjusted hazard ratio, 1.87; 95% confidence
      interval, 1.49-2.34; Ptrend < 0.001), but not with risk of carcinoma with poorly
      differentiated foci (Ptrend = 0.56). This differential association appeared to be
      consistent in strata of tumor microsatellite instability or FASN expression
      status, although the statistical power was limited. The association between BMI
      and colorectal carcinoma risk did not significantly differ by overall tumor
      differentiation, mucinous differentiation, or signet ring cell component
      (Pheterogeneity > 0.03, with the adjusted alpha of 0.01). High BMI was associated
      with risk of colorectal cancer subtype containing no poorly-differentiated focus.
      Our findings suggest that carcinogenic influence of excess energy balance might
      be stronger for tumors that retain better intestinal differentiation throughout
      the tumor areas.

PMID- 28510101
TI  - A critical analysis of cancer biobank practices in relation to biospecimen
      quality.
AB  - There are concerns that a substantial proportion of published research data is
      not reproducible, which may partially explain the frequent failure to translate
      pre-clinical results to clinical care. High-quality cancer biospecimens are
      needed for robust, reproducible research findings, with most researchers
      obtaining these specimens from cancer biobanks or tumour banks. This review
      provides an overview of the types of quality control (QC) activities conducted
      within cancer biobanks that pertain to biospecimen quality and of biospecimen
      quality reporting tools, including SPREC and BRISQ. We examine how QC assay
      results and other biospecimen data are communicated from biobanks to researchers,
      and whether these activities lead to improved biospecimen quality reporting
      within the literature and/or to improved research outcomes. We also discuss
      operational factors that limit QC activities within biobanks and evidence gaps
      requiring further research. In summary, whereas the provision of quality
      biospecimens is a common aim of cancer biobanks, QC activities remain
      underreported and are rarely discussed in the literature, compared with other
      aspects of biobank operations. Further research is required to determine how
      biobanks can most efficiently optimise biospecimen quality, and how communication
      between biobanks and researchers can be improved.

PMID- 28510102
TI  - Natural isoquinoline alkaloids: binding aspects to functional proteins, serum
      albumins, hemoglobin, and lysozyme.
AB  - The putative anticancer alkaloids berberine, palmatine, jatrorrhizine, and
      sanguinarine are known to bind to nucleic acids. To develop them as potential
      drugs for therapeutic use, their binding affinity to functional proteins and mode
      of transport in the circulatory system need to be clearly understood. Towards
      this, many studies on their binding aspects to proteins have been reported and a
      considerable amount of data, mostly of biophysical nature, exists in the
      literature. The importance of these natural isoquinoline alkaloids and the recent
      literature on their interaction phenomena with functional proteins, serum
      albumins, hemoglobin, and lysozyme are presented in this review.

PMID- 28510103
TI  - Optically-controlled platforms for transfection and single- and sub-cellular
      surgery.
AB  - Improving the resolution of biological research to the single-cell or sub
      cellular level is of critical importance in a wide variety of processes and
      disease conditions. Most obvious are those linked to aging and cancer, many of
      which are dependent upon stochastic processes where individual, unpredictable
      failures or mutations in individual cells can lead to serious downstream
      conditions across the whole organism. The traditional tools of biochemistry
      struggle to observe such processes: the vast majority are based upon ensemble
      approaches analysing the properties of bulk populations, which means that details
      of individual constituents is lost. What are required, then, are tools with the
      precision and resolution to probe and dissect cells at the single-micron scale:
      the scale of the individual organelles and structures that control their
      function. In this review, we highlight the use of highly-focused laser beams to
      create systems which provide precise control and specificity at the single-cell
      or even single-micron level. The intense focal points generated can directly
      interact with cells and cell membranes, which in conjunction with related
      modalities such as optical trapping provide a broad platform for the development
      of single-cell and sub-cellular surgery approaches. These highly tuneable tools
      have been demonstrated to deliver or remove material from cells of interest, and
      they can simultaneously excite fluorescent probes for imaging purposes or
      plasmonic structures for very local heating. We discuss both the history and
      recent applications of the field, highlighting the key findings and developments
      over the last 40 years of biophotonics research.

PMID- 28510105
TI  - Agrochemical loading in drains and rivers and its connection with pollution in
      coastal lagoons of the Mexican Pacific.
AB  - The state of Sinaloa in Mexico is an industrialized agricultural region with a
      documented pesticide usage of 700 t year-1; which at least 17 of the pesticides
      are classified as moderately to highly toxic. Pollutants in the water column of
      rivers and drains are of great concern because the water flows into coastal
      lagoons and nearshore waters and thereby affects aquatic organisms. This study
      was done in four municipalities in the state of Sinaloa that produce food
      intensively. To investigate the link between pollution in the lagoons and their
      proximity to agricultural sites, water was sampled in three coastal lagoons and
      in the rivers and drains that flow into them. Seawater from the Gulf of
      California, 10 km from the coast, was also analyzed. Concentrations of nutrients,
      organochlorines, and organophosphorus pesticides were determined. Nutrient
      determination showed an unhealthy environment with N/P ratios of <16, thus
      favoring nitrogen-fixing cyanobacteria. The organochlorine pesticides showed a
      clear accumulation in the coastal lagoons from the drains and rivers, with
      SigmaHCH showing the highest concentrations. In the southern part of the region
      studied, pollution of the coastal lagoon of Pabellones could be traced mainly to
      the drains from the agricultural sites. Accumulation of OC pesticides was also
      observed in the Gulf of California. Tests for 22 organophosphates revealed only
      five (diazinon, disulfoton, methyl parathion, chlorpyrifos, and mevinphos);
      diazinon was detected at all the sites, although methyl parathion was present at
      some sites at concentrations one order of magnitude higher than diazinon.

PMID- 28510106
TI  - The pollution characteristics of PM2.5 and correlation analysis with
      meteorological parameters in Xinxiang during the Shanghai Cooperation
      Organization Prime Ministers' Meeting.
AB  - The pollution characteristics of PM2.5 and correlation analysis with
      meteorological parameters in Xinxiang during the Shanghai Cooperation
      Organization Prime Ministers' Meeting were investigated. During the whole
      meeting, nine PM2.5 samples were collected at a suburban site of Xinxiang, and
      the average concentration of PM2.5 was 122.28 MUg m-3. NO3-, NH4+, SO42-
      accounted for 56.8% of the total water-soluble ions. In addition, with an
      exception of Cl-, all of water-soluble ions decreased during the meeting. Total
      concentrations of crustal elements ranged from 6.53 to 185.86 MUg m-3, with an
      average concentration of 52.51 MUg m-3, which accounted for 82.5% of total
      elements. The concentrations of organic carbon and elemental carbon were 7.71 and
      1.52 MUg m-3, respectively, lower than those before and after the meeting. It is
      indicated that during the meeting, limiting motor vehicles is to reduce exhaust
      emissions, delay heating is to reduce the fossil fuel combustion, and other
      measures are to reduce the concentration of PM2.5. The directly dispersing by
      mixing layer height increase and the indirectly reducing the formation of
      secondary aerosol by low relative humidity, and these are the only two key
      removing mechanisms of PM2.5 in Xinxiang during the meeting.

PMID- 28510107
TI  - Allosteric movements in eubacterial RecA.
AB  - The action of RecA, an important eubacterial protein involved in recombination
      and repair, involves the transition from an inactive filament in the absence of
      DNA to an active filament formed in association with DNA and ATP. The structure
      of the inactive filament was first established in Escherichia coli RecA (EcRecA).
      The interaction of RecA with non-hydrolysable ATP analogues and ADP has been
      thoroughly characterized and the DNA binding loops visualized based on the
      crystal structures of the RecA proteins from Mycobacterium tuberculosis (MtRecA)
      and Mycobacterium smegmatis (MsRecA). A switch residue, which triggers the
      transformation of the information on ATP binding to the DNA binding regions, has
      been identified. The 20-residue C-terminal stretch of RecA, which is disordered
      in all other relevant crystal structures, has been defined in an MsRecA-dATP
      complex. The ordering of the stretch is accompanied by the generation of a new
      nucleotide binding site which can communicate with the original nucleotide
      binding site of an adjacent molecule in the filament. The plasticity of MsRecA
      and its mutants involving the switch residue has been explored by studying
      crystals grown under different conditions at two different temperatures and, in
      one instance, at low humidity. The structures of these crystals and those of
      EcRecA and Deinococcus radiodurans RecA (DrRecA) provide information on
      correlated movements involving different regions of the molecule. These
      correlated movements appear to be important in the allosteric transitions of RecA
      during its action.

PMID- 28510109
TI  - A new theoretical approach to biological self-assembly.
AB  - Upon biological self-assembly, the number of accessible translational
      configurations of water in the system increases considerably, leading to a large
      gain in water entropy. It is important to calculate the solvation entropy of a
      biomolecule with a prescribed structure by accounting for the change in water
      water correlations caused by solute insertion. Modeling water as a dielectric
      continuum is not capable of capturing the physical essence of the water entropy
      effect. As a reliable tool, we propose a hybrid of the angle-dependent integral
      equation theory combined with a multipolar water model and a morphometric
      approach. Using our methods wherein the water entropy effect is treated as the
      key factor, we can elucidate a variety of processes such as protein folding,
      cold, pressure, and heat denaturating of a protein, molecular recognition,
      ordered association of proteins such as amyloid fibril formation, and functioning
      of ATP-driven proteins.

PMID- 28510108
TI  - Application and use of differential scanning calorimetry in studies of thermal
      fluctuation associated with amyloid fibril formation.
AB  - The aggregation of proteins into amyloid fibrils is a topic that has attracted
      great interest because the process is associated with the pathology of numerous
      human diseases. Despite considerable progress in the elucidation of the structure
      of amyloid fibrils and the kinetic mechanism of their formation, knowledge on the
      thermodynamic aspects underlying the formation and stability of amyloid fibrils
      is limited. In this review, we summarize recent calorimetric studies of amyloid
      fibril formation, with the goal of obtaining a better understanding of the causal
      factors that thermally induce proteins to aggregate into amyloid fibrils.
      Calorimetric data show that differential scanning calorimetry is a useful
      technique to study the causative factors that thermally trigger the conversion to
      the amyloid structure and highlight the physics related to the thermal
      fluctuation of proteins during this conversion.

PMID- 28510110
TI  - Principles of multiparametric optimization for phospholipidomics by 31P NMR
      spectroscopy.
AB  - Phospholipids have long been known to be the principal constituents of the
      bilayer matrix of cell membranes. While the main function of cell membranes is to
      provide physical separation between intracellular and extracellular compartments,
      further biological and biochemical functions for phospholipids have been
      identified more recently, notably in cell signaling, cell recognition and cell
      cell interaction, but also in cell growth, electrical insulation of neurons and
      many other processes. Therefore, accurate and efficient determination of tissue
      phospholipid composition is essential for our understanding of biological tissue
      function. 31P NMR spectroscopy is a quantitative and fast method for analyzing
      phospholipid extracts from biological samples without prior separation. However,
      the number of phospholipid classes and subclasses that can be quantified
      separately and reliably in 31P NMR spectra of tissue extracts is critically
      dependent on a variety of experimental conditions. Until recently, little
      attention has been paid to the optimization of phospholipid 31P NMR spectra. This
      review surveys the basic physicochemical properties that determine the quality of
      phospholipid spectra, and describes an optimization strategy based on this
      assessment. Notably, the following experimental parameters need to be controlled
      for systematic optimization: (1) extract concentration, (2) concentration of
      chelating agent, (3) pH value of the aqueous component of the solvent system, and
      (4) temperature of the NMR measurement. We conclude that a multiparametric
      optimization approach is crucial to obtaining highly predictable and reproducible
      31P NMR spectra of phospholipids.

PMID- 28510104
TI  - Historical perspective on heart function: the Frank-Starling Law.
AB  - More than a century of research on the Frank-Starling Law has significantly
      advanced our knowledge about the working heart. The Frank-Starling Law mandates
      that the heart is able to match cardiac ejection to the dynamic changes occurring
      in ventricular filling and thereby regulates ventricular contraction and
      ejection. Significant efforts have been attempted to identify a common
      fundamental basis for the Frank-Starling heart and, although a unifying idea has
      still to come forth, there is mounting evidence of a direct relationship between
      length changes in individual constituents (cardiomyocytes) and their sensitivity
      to Ca2+ ions. As the Frank-Starling Law is a vital event for the healthy heart,
      it is of utmost importance to understand its mechanical basis in order to
      optimize and organize therapeutic strategies to rescue the failing human heart.
      The present review is a historic perspective on cardiac muscle function. We
      "revive" a century of scientific research on the heart's fundamental protein
      constituents (contractile proteins), to their assemblies in the muscle (the
      sarcomeres), culminating in a thorough overview of the several synergistically
      events that compose the Frank-Starling mechanism. It is the authors' personal
      beliefs that much can be gained by understanding the Frank-Starling relationship
      at the cellular and whole organ level, so that we can finally, in this century,
      tackle the pathophysiologic mechanisms underlying heart failure.

PMID- 28510111
TI  - Toward a molecular understanding of the photosensitizer-copper interaction for
      tumor destruction.
AB  - The aim of this study was to shown that the photosensitizer in photodynamic
      therapy (PDT) can contribute to the dark toxicity and phototoxicity of the tumor
      by binding with copper. This binding process can remove the copper from the body,
      stopping angiogenesis as well as activating the mechanisms of cell death, such as
      apoptosis and necrosis. In PDT, this coupling may be considered a new route for
      fighting cancer in addition to those already known which involve reactive oxygen
      species.

PMID- 28510112
TI  - Application of advanced fluorescence microscopy to the structure of meiotic
      chromosomes.
AB  - Chromosomes undergoing meiosis are defined by a macromolecular protein assembly
      called the synaptonemal complex which holds homologs together and carries out
      important meiotic functions. By retaining the molecular specificity, multiplexing
      ability, and in situ imaging capabilities of fluorescence microscopy, but with
      vastly increased resolution, 3D-SIM and other superresolution techniques are
      poised to make significant discoveries about the structure and function of the
      synaptonemal complex. This review discusses recent developments in this field and
      poses questions approachable with current and future technology.

PMID- 28510113
TI  - Stochastic chemical kinetics : A review of the modelling and simulation
      approaches.
AB  - A review of the physical principles that are the ground of the stochastic
      formulation of chemical kinetics is presented along with a survey of the
      algorithms currently used to simulate it. This review covers the main literature
      of the last decade and focuses on the mathematical models describing the
      characteristics and the behavior of systems of chemical reactions at the nano-
      and micro-scale. Advantages and limitations of the models are also discussed in
      the light of the more and more frequent use of these models and algorithms in
      modeling and simulating biochemical and even biological processes.

PMID- 28510115
TI  - Application of Decellularized Tissue Scaffolds in Ovarian Tissue Transplantation.
AB  - In tissue engineering, decellularized scaffolds have been proved to have
      remarkable capacity to promote regeneration in various organs such as kidney,
      heart, lung, and liver. Marrying the field of cryobiology and reproductive
      medicine resulted in considerable progress and breakthroughs, which led to the
      emergence of ovarian tissue cryopreservation and transplantation as a promising
      option for fertility preservation. Here we describe an innovative application of
      decellularized tissue scaffolds as a regenerative platform for reconstruction of
      ovarian grafts for auto-transplantation.

PMID- 28510114
TI  - Fabricating poly(1,8-octanediol citrate) elastomer based fibrous mats via
      electrospinning for soft tissue engineering scaffold.
AB  - Poly(1,8-octanediol citrate) (POC) is a recently developed biodegradable
      crosslinked elastomer that possesses good cytocompatibility and matchable
      mechanical properties to soft tissues. However, the thermosetting characteristic
      reveals a big challenge to manufacture its porous scaffold. Herein, POC elastomer
      was electrospun into fiber mat using poly(L-lactic acid) (PLLA) as a spinnable
      carrier. The obtained POC/PLLA fiber mats were characterized by scanning electron
      microscopy (SEM), dynamic mechanical analysis (DMA), uniaxial tensile test,
      static-water-contact-angle, thermal analysis, in vitro degradation and
      biocompatibility test. It was found that the fibrous structure could be formed so
      long as the POC pre-polymer's content was no more than 50 wt%. The presence of
      elastic POC component not only strengthened the fiber mats but also toughened the
      fiber mats. The hydrophilicity of 50/50 fiber mat significantly improved. In
      vitro degradation rate of POC based fiber mats was much faster than that of pure
      PLLA. Cyto- and histo-compatibility tests confirmed that the POC/PLLA fiber mats
      had good biocompatibility for potential applications in soft tissue engineering.

PMID- 28510117
TI  - Novex-3, the tiny titin of muscle.
AB  - The giant multi-functional striated muscle protein titin is the third most
      abundant muscle protein after myosin and actin. Titin plays a pivotal role in
      myocardial passive stiffness, structural integrity and stress-initiated signaling
      pathways. The complete sequence of the human titin gene contains three isoform
      specific mutually exclusive exons [termed novel exons (novex)] coding for the I
      band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48).
      Transcripts containing either the novex-1 or novex-2 exons code for the novex-1
      and novex-2 titin isoforms. The novex-3 transcript contains a stop codon and
      polyA tail signal, resulting in an unusually small (~700 kDa) isoform, referred
      to as novex-3 titin. This 'tiny titin' isoform extends from the Z-disc (N
      terminus) to novex-3 (C-terminus) and is expressed in all striated muscles.
      Biochemical analysis of novex-3 titin in cardiomyocytes shows that obscurin, a
      vertebrate muscle protein, binds to novex-3 titin. The novex-3/obscurin complex
      localizes to the Z-disc region and may regulate calcium, and SH3- and GTPase
      associated myofibrillar signaling pathways. Therefore, novex-3 titin could be
      involved in stress-initiated sarcomeric restructuring.

PMID- 28510116
TI  - Obscure functions: the location-function relationship of obscurins.
AB  - The obscurin family of polypeptides is essential for normal striated muscle
      function and contributes to the pathogenesis of fatal diseases, including
      cardiomyopathies and cancers. The single mammalian obscurin gene, OBSCN, gives
      rise to giant (~800 kDa) and smaller (~40-500 kDa) proteins that are composed of
      tandem adhesion and signaling motifs. Mammalian obscurin proteins are expressed
      in a variety of cell types, including striated muscles, and localize to distinct
      subcellular compartments where they contribute to diverse cellular processes.
      Obscurin homologs in Caenorhabditis elegans and Drosophila possess a similar
      domain architecture and are also expressed in striated muscles. The long sought
      after question, "what does obscurin do?" is complex and cannot be addressed
      without taking into consideration the subcellular distribution of these proteins
      and local isoform concentration. Herein, we present an overview of the functions
      of obscurins and begin to define the intricate relationship between their
      subcellular distributions and functions in striated muscles.

PMID- 28510120
TI  - Obscurin variants and inherited cardiomyopathies.
AB  - The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM), dilated
      cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), have been
      frequently associated with mutations in sarcomeric proteins. In recent years,
      advances in DNA sequencing technology has allowed the study of the giant proteins
      of the sarcomere, such as titin and nebulin. Obscurin has been somewhat neglected
      in these studies, largely because its functional role is far from clear, although
      there was an isolated report in 2007 of obscurin mutations associated with HCM.
      Recently, whole exome sequencing methodology (WES) has been used to address
      mutations in OBSCN, the gene for obscurin, and OBSCN variants were found to be
      relatively common in inherited cardiomyopathies. In different studies, 5 OBSCN
      unique variants have been found in a group of 30 end-stage failing hearts, 6
      OBSCN unique variants in 74 HCM cases and 3 OBSCN unique variants in 10 LVNC
      patients. As yet, the number of known potentially disease-causing OBSCN variants
      is quite small. The reason for this is that mutations in the OBSCN gene have not
      been recognised as potentially disease-causing until recently, and were not
      included in large-scale genetic surveys. OBSCN mutations may be causative of HCM,
      DCM and LVNC and other cardiomyopathies, or they may work in concert with other
      variants in the same or other genes to initiate the pathology. Currently, the
      function of obscurin is not well understood, but we anticipate that many more
      OBSCN variants linked to cardiomyopathy will be found when the large cohorts of
      patient sequences available are tested. It is to be hoped that the establishment
      of the importance of obscurin in pathology will stimulate a thorough
      investigation of obscurin function.

PMID- 28510118
TI  - Tampering with springs: phosphorylation of titin affecting the mechanical
      function of cardiomyocytes.
AB  - Reversible post-translational modifications of various cardiac proteins regulate
      the mechanical properties of the cardiomyocytes and thus modulate the contractile
      performance of the heart. The giant protein titin forms a continuous filament
      network in the sarcomeres of striated muscle cells, where it determines passive
      tension development and modulates active contraction. These mechanical properties
      of titin are altered through post-translational modifications, particularly
      phosphorylation. Titin contains hundreds of potential phosphorylation sites, the
      functional relevance of which is only beginning to emerge. Here, we provide a
      state-of-the-art summary of the phosphorylation sites in titin, with a particular
      focus on the elastic titin spring segment. We discuss how phosphorylation at
      specific amino acids can reduce or increase the stretch-induced spring force of
      titin, depending on where the spring region is phosphorylated. We also review
      which protein kinases phosphorylate titin and how this phosphorylation affects
      titin-based passive tension in cardiomyocytes. A comprehensive overview is
      provided of studies that have measured altered titin phosphorylation and titin
      based passive tension in myocardial samples from human heart failure patients and
      animal models of heart disease. As our understanding of the broader implications
      of phosphorylation in titin progresses, this knowledge could be used to design
      targeted interventions aimed at reducing pathologically increased titin stiffness
      in patients with stiff hearts.

PMID- 28510121
TI  - Can glypican-3 be a disease-specific biomarker?
AB  - BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been
      identified as a potential biomarker candidate in hepatocellular carcinoma, lung
      carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The
      aim of our review is to evaluate whether GPC3 has utility as a disease-specific
      biomarker, to discuss the potential involvement of GPC3 in cell biology, and to
      consider the changes of GPC3 gene and protein expression and regulation in
      hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS. RESULTS:
      Immunohistochemical studies have suggested that over-expression of GPC3 is
      associated with a poorer prognosis for hepatocellular carcinoma patients.
      Expression of GPC3 leads to an increased apoptosis response in human lung
      carcinoma tumor cells, and is considered to be a candidate lung tumor suppressor
      gene. Increased serum levels of GPC3 have been demonstrated in ARDS patients with
      severe pneumonia. CONCLUSIONS: Glypican-3 could be considered as a clinically
      useful biomarker in hepatocellular carcinoma, lung carcinoma, and ARDS, but
      further research is needed to confirm and expand on these findings.

PMID- 28510119
TI  - Genetic epidemiology of titin-truncating variants in the etiology of dilated
      cardiomyopathy.
AB  - Heart failure (HF) is a complex clinical syndrome defined by the inability of the
      heart to pump enough blood to meet the body's metabolic demands. Major causes of
      HF are cardiomyopathies (diseases of the myocardium associated with mechanical
      and/or electrical dysfunction), among which the most common form is dilated
      cardiomyopathy (DCM). DCM is defined by ventricular chamber enlargement and
      systolic dysfunction with normal left ventricular wall thickness, which leads to
      progressive HF. Over 60 genes are linked to the etiology of DCM. Titin (TTN) is
      the largest known protein in biology, spanning half the cardiac sarcomere and, as
      such, is a basic structural and functional unit of striated muscles. It is
      essential for heart development as well as mechanical and regulatory functions of
      the sarcomere. Next-generation sequencing (NGS) in clinical DCM cohorts
      implicated truncating variants in titin (TTNtv) as major disease alleles,
      accounting for more than 25% of familial DCM cases, but these variants have also
      been identified in 2-3% of the general population, where these TTNtv blur
      diagnostic and clinical utility. Taking into account the published TTNtv and
      their association to DCM, it becomes clear that TTNtv harm the heart with
      position-dependent occurrence, being more harmful when present in the A-band TTN,
      presumably with dominant negative/gain-of-function mechanisms. However, these
      insights are challenged by the depiction of position-independent toxicity of
      TTNtv acting via haploinsufficient alleles, which are sufficient to induce
      cardiac pathology upon stress. In the current review, we provide an overview of
      TTN and discuss studies investigating various TTN mutations. We also present an
      overview of different mechanisms postulated or experimentally validated in the
      pathogenicity of TTNtv. DCM-causing genes are also discussed with respect to non
      truncating mutations in the etiology of DCM. One way of understanding pathogenic
      variants is probably to understand the context in which they may or may not
      affect protein-protein interactions, changes in cell signaling, and substrate
      specificity. In this regard, we also provide a brief overview of TTN interactions
      in situ. Quantitative models in the risk assessment of TTNtv are also discussed.
      In summary, we highlight the importance of gene-environment interactions in the
      etiology of DCM and further mechanistic studies used to delineate the pathways
      which could be targeted in the management of DCM.

PMID- 28510122
TI  - Anti-thyroglobulin antibodies do not significantly increase the risk of finding
      iodine avid metastases on post-radioactive iodine ablation scan in low-risk
      thyroid cancer patients.
AB  - OBJECTIVE: Post-operative thyroglobulin (Tg) levels can predict the likelihood of
      residual cancer, including distant metastases, thereby influencing postsurgical
      treatment strategies even in patients with low-risk disease. Circulating anti
      thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing
      this clinical use. It is not known if the presence of anti-Tg Abs predicts
      metastatic disease on post-therapy scan in patients with low-risk disease or if
      they should influence the use or dose of I-131 therapy. In the present study, we
      compare post-therapy scans in low-risk patients with and without anti-Tg Abs.
      METHODS: This is a single-institution retrospective study. The study population
      (Group A) included all patients with low-risk differentiated thyroid cancer (DTC)
      who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with
      intrathyroidal T1-T2, Nx, N0 or N1a (<=5 nodes all measuring, when reported, <2
      mm) that had anti-thyroglobulin antibodies. Patients were excluded if they had
      known distant metastases and/or extensive vascular invasion. A second group of
      patients (Group B) treated during the same period but without anti-Tg antibodies
      was selected to match group A by propensity core matching with a logistic
      regression model. RESULTS: Each group included 37 patients. In group A: Median
      age was 40 years, 86% female and 76% PTC. Median tumor size was 2 cm (0.2-3.8),
      32% had multifocal disease, 16% were N1a and 4% had vascular invasion. Parameters
      in group B were not statistically different from Group A, as expected based on
      the selection criteria, except being less likely to have Hashimoto's thyroiditis
      on pathology (p < 0.001). Post-therapy scan results were compared by Chi-square
      test with 86% negative post therapy scan frequency in group A and 92% in group B
      without evidence of a difference (p = 0.45). CONCLUSION: In patients with low
      risk DTC, anti-Tg Abs did not significantly predict metastatic disease on post
      therapy scan. If confirmed, these data suggest that the presence of anti-Tg Abs
      alone should not influence initial therapy in patients with low-risk DTC.

PMID- 28510123
TI  - Alzheimer's disease Abeta42 peptide induces an increase in Na,K-ATPase
      glutathionylation.
AB  - We have shown that the inhibition of Na,K-ATPase during its long-term incubation
      with amyloid beta (Abeta42), an Alzheimer's disease protein, is caused by the
      change in the thiol redox status of cells leading to induction of
      glutathionylation alpha-subunit of Na,K-ATPase. To restore the activity of Na,K
      ATPase, it is proposed to use reducing agents, which promote normalization of the
      redox status of cells and deglutathionylation of the protein.

PMID- 28510124
TI  - Computer-aided estimation of the hERG-mediated cardiotoxicity risk of potential
      drug components.
AB  - The hERG potassium channel is one of the most important anti-targets determining
      cardiotoxicity of potential drugs. Using fragmental descriptors and artificial
      neural networks, the predictive models of the relationship between the structure
      of organic compounds and their activity with respect to hERG were built, and the
      structural factors affecting it were analyzed. By their predictive ability and
      applicability domain, these models (N = 1000, Q 2 = 0.77, RMSE cv = 0.45 for
      affinity and N = 2886, Q 2 = 0.60, RMSE cv = 0.55 for channel inhibition) are
      superior to the previously published models and can be used to minimize the risk
      of cardiotoxicity during drug development.

PMID- 28510125
TI  - Molecular design of proneurogenic and neuroprotective compounds-allosteric NMDA
      receptor modulators.
AB  - N-Methyl-D-aspartic acid (NMDA) receptor is a promising target for treatment of
      neurodegenerative diseases and other brain disorders as well as for designing
      proneurogenic compounds able to stimulate neurogenesis in adult brain. We
      analyzed the structure of the binding site of negative allosteric modulators in
      the amino-terminal domain of the NMDA receptor and identified possible modes of
      their binding as well as performed molecular design of new modulators that
      significantly differ from the known ones in structure and binding mode. In
      addition, we formed a focused library of chemical compounds with potential
      neuroprotective and proneurogenic properties, desirable set of pharmacokinetic
      properties, and low toxicity, which can be the basis for development of new
      generation drugs.

PMID- 28510126
TI  - Dehydrin stress proteins in Pinus sylvestris L. needles under conditions of
      extreme climate of Yakutia.
AB  - This is the first study to investigate stress proteins dehydrins with the use of
      specific antibodies in the Scots pine (Pinus sylvestris L.) needles and their
      changes in the annual cycle under extreme climate of Yakutia. No pronounced
      polymorphism of major dehydrins (14-15 and 66 kDa) has been found during the
      winter dormancy period of P. sylvestris. A clear correlation between the seasonal
      variations in dehydrins and changes in the water content in needles was revealed.
      Consistently high levels of dehydrins was retained throughout the period of low
      negative temperatures. It is assumed that dehydrins can participate in the
      formation of P. sylvestris L. resistance to the permafrost conditions.

PMID- 28510127
TI  - Negative-sense virion RNA of segment 8 (NS) of influenza a virus is able to
      translate in vitro a new viral protein.
AB  - It was shown that full-length virion RNA of segment 8 of influenza virus
      A/Aichi/2/68 (H3N2) can initiate the synthesis of two major polypeptides with
      molecular weights of 23 and 13 kD and a minor polypeptide with a molecular weight
      of 19 kDa, which specifically reacted with the antibodies to the 30-membered
      peptide of the central part of the NSP protein of influenza A virus. Thus, the
      genomic-polarity RNA of segment 8 of influenza virus A has a translational
      template function. These data provide further confirmation of the concept of the
      bipolar (ambisens) strategy of functioning of the influenza A virus genome.

PMID- 28510128
TI  - Specific character of bacterial biodegradation of polyhydroxyalkanoates with
      different chemical structure in soil.
AB  - The study addresses the influence of the physicochemical properties of the
      reserve cellular macromolecules (polyhydroxyalkanoates, PHA) with different
      chemical composition on their biodegradation in the agro-transformed field soil
      of the Siberian region (Krasnoyarsk Territory, Russia). It was shown that the
      degradation of the PHA samples depends on the degree of polymer crystallinity
      (Cx). For the first time, it was shown that the range of PHA-degrading
      microorganisms differs for each of PHA types. The study defines the primary
      degraders specific to each PHA type and common to all types of examined polymers.

PMID- 28510129
TI  - LTR sequence of the MDG4 retrotransposon contains the MAD protein binding site
      that affects the east-dependent repression.
AB  - Earlier, we showed in a model system of the yellow gene of D. melanogaster that
      an increase in the EAST protein concentration leads to repression in bristles,
      the mechanism of which remained obscure. In this study, an inverted repeat was
      localized by genetic methods in the long terminal repeat (LTR) sequence of the
      MDG4 retrotransposon. This repeat includes the binding site for the Mad protein
      the key component of the of TGF-beta/BMP signaling cascade. The results of this
      work suggest that the Mad protein recruits to chromatin a regulatory complex that
      functionally interacts with the EAST protein. This complex either itself
      suppresses the yellow gene expression in bristles or moves the transgene to the
      nuclear regions with a high concentration of transcription repression factors.

PMID- 28510130
TI  - The penetration of 5-oxo-Pro-Arg-Pro into the brain and the major metabolic
      pathways of this peptide in the rat brain and blood at the intranasal and
      intravenous administration.
AB  - It was shown that the neuroactive peptide 5-oxo-Pro-Arg-Pro (5-oxo-PRP) is
      detected in the brain in the time interval of 5-120 min after it was
      intravenously or intranasally administered to rats; the maximum concentration of
      labeled tripeptide in these modes of administration was observed after 30 and 10
      min, respectively. A significant difference in the concentrations of 5-oxo-PRP in
      the blood and brain (the latter was 50 times lower) during intravenous
      administration indicates a relatively low permeability of the peptide across the
      blood-brain barrier. Pharmacokinetic data analysis showed that, when administered
      intranasally, approximately 45% of the total number of 5-oxo-PRP detectable in
      the brain in the entire period of study enters via transport from the nasal
      cavity, and the rest of the peptide enters through the blood-brain barrier from
      the blood stream. It was found that 5-oxo-PRP in rats is rapidly metabolized
      forming proteolytic products, mainly amino acids, and degradation products,
      presumably oxidized these amino acids.

PMID- 28510131
TI  - Generation of radical form of dipyridamole at illumination of photosynthetic
      reaction centers of Rb. sphaeroides.
AB  - The study of the effect of vasodilator, antiplatelet agent, and inhibitor P
      glycoprotein dipyridamole (DIP) on the functioning of the transmembrane protein
      of the reaction center (RC) of Rb. sphaeroides showed that the activation of RC
      by constant light generates the DIP radical cation, which significantly affects
      the kinetics of recombination of charges divided between photoactive
      bacteriochlorophyll and quinone acceptors. Thus, the antioxidant properties of
      DIP may affect the functional activity of membrane proteins, and this apparently
      should be taken into account in the studies of the mechanisms of therapeutic
      action of this drug.

PMID- 28510132
TI  - Methyl-beta-cyclodextrin modulates thapsigargin-induced store-dependent Ca2+
      entry in macrophages.
AB  - Using Fura-2AM microfluorimetry, we have shown for the first time that
      preincubation of macrophages with methyl-beta-cyclodextrin, inducing cholesterol
      extraction from membranes and raft disruption, leads to significant inhibition of
      thapsigargin-induced store-dependent Ca2+ entry in rat peritoneal macrophages. In
      contrast, macrophage treatment with methyl-beta-cyclodextrin after Ca2+ entry
      mechanisms were activated by store depletion by thapsigargin application leads to
      potentiation of subsequent store-dependent Ca2+ entry. The results suggest that
      intact lipid rafts are necessary for the activation but not the maintenance of
      store-dependent Ca2+ entry in macrophages.

PMID- 28510133
TI  - Analysis of immune-biochemical indicators to assess the risk of developing
      cardiological pathology.
AB  - Prognostic immuno-biochemical tests to assess the severity of the condition of
      patients with cardiac diseases were developed. A comparative analysis of clinical
      and laboratory blood parameters, which are used in practice for the diagnosis and
      prognosis of diseases, and an analysis of the content of natural antibodies (n
      Abs) to beta-endorphin, bradykinin, histamine, dopamine, and serotonin were
      performed. A significant correlation between the level of n-Abs, the main
      biochemical parameters, and the content of blood corpuscles was revealed. The
      practical importance of the combined use of immunological and biochemical tests
      to increase the reliability of prediction of the severity of heart pathologies
      was established.

PMID- 28510134
TI  - Paramagnetics melanin and Mn2+ in black soldier fly Hermetia illucens.
AB  - Larva, prepupa (last instar larva), pupa, and an empty shell of pupa after
      hatching of the black soldier fly Hermetia illucens contain eumelanin, an active
      synthesis of which is observed at the prepupal stage, which is probably due to
      the release of prepupa from the feed substrate thickness to the open space for
      pupation. It was shown for the first time that prepupa contains high quantities
      of the magnetically active form of manganese Mn2+. This fact indicates that Mn2+
      stimulates the copper-containing tyrosinase-the key enzyme in the synthesis of
      melanin in the period of migration and adaptation of the insect to the solar
      radiation.

PMID- 28510135
TI  - Immune response to Vi-antigen of Salmonella typhi is dependent on introduction of
      positive charge and shape of charged group into polysaccharide.
AB  - A model of a controlled conversion of polysaccharide Vi-antigen of S. typhi into
      zwitterionic antigen is proposed. The immunological properties of modifications
      of this antigen conjugated to a protein support were studied.

PMID- 28510136
TI  - Identification and expression analysis of chitinase genes in parasitic plant
      Monotropa hypopitys.
AB  - Genes encoding six chitinases, five of which belong to classes I (MhCHI3 and
      MhCHI4), IV (MhCHI1), V (MhCHI5), and VII (MhCHI2), were identified in the
      transcriptome of the parasitic mixoheterotrophic plant Monotropa hypopitys. The
      transcription level of MhCHI5 and MhCHI1 was low; however, in the leaves (bracts)
      and roots it was higher than in flowers. MhCHI4 transcripts were detected
      primarily in the flowers and were almost absent in the roots, whereas the
      expression level of MhCHI3 was relatively high in all organs but maximum in the
      leaves (bracts).

PMID- 28510137
TI  - Possible mechanism of bursting suppression in nociceptive neurons.
AB  - The use of the mathematical model of rat nociceptive neuron membrane allowed us
      to predict a new mechanism of suppression of ectopic bursting discharges, which
      arise in neurons of dorsal root ganglia and are one of the causes of neuropathic
      pain. The treatment with comenic acid leads to switching off the ectopic bursting
      discharges due to a decrease in the effective charge transferring via the
      activation gating structure of the slow sodium channels (Na V1.8a). Comenic acid
      is a drug substance of a new non-opioid analgesic [1] Thus, this analgesic not
      only reduces the frequency of rhythmic discharges of nociceptive neuron membrane
      [2] but also it suppresses its ectopic bursting discharges.

PMID- 28510138
TI  - Antitumor efficacy of Auger electron emitter 111In delivered by modular
      nanotransporter into the nuclei of cells with folate receptor overexpression.
AB  - A new modular nanotransporter (MNT) for the delivery of anticancer agents into
      the nuclei of cells with folate receptor overexpression was created. An effective
      method for acceding labeling of this MNT with Auger electron emitter 111In has
      been developed. A significant therapeutic effect was observed after a single
      intratumoral injection of the new 111In-labeled MNT to mice grafted with human
      cervical carcinoma characterized by folate receptor overexpression.

PMID- 28510139
TI  - Development of target delivery system based on actinomycin class drugs and
      recombinant alpha-fetoprotein.
AB  - A recombinant alpha-fetoprotein (rAFP) was obtained in the yeast P. pastoris
      system, and its functional activity was confirmed. A method for producing polymer
      particles loaded with dactinomycin was developed, and a conjugate of these
      nanoparticles with rAFP was synthesized. The efficiency of the obtained conjugate
      on the HeLa, SKOV3, and MG-63 tumor cells and the absence of toxicity on the
      normal cells was shown. Experiments in vivo demonstrated a significant increase
      in the antitumor efficacy of the conjugate at a lower general toxicity as
      compared to the commercially available dactinomycin.

PMID- 28510140
TI  - Nuclear receptors EcR, Usp, E75, DHR3, and ERR regulate transcription of ecdysone
      cascade genes.
AB  - We found that an increase in the expression level of E75, DHR3, and ERR increases
      the degree of activation of dhr3 and hr4 genes in Drosophila S2 cells. We also
      detected a repressing effect of these nuclear receptors on the basal
      transcription level of these genes. This is the first study to show the ability
      of nuclear receptors E75, DHR3, and ERR to function as activators or repressors
      depending on external conditions. We also confirmed the existence of the
      interaction of all studied nuclear receptors with the promoters of dhr3 and hr4
      genes of the ecdysone cascade in vivo.

PMID- 28510141
TI  - Sunscreens: An Update.
AB  - Sunscreens have been widely used by the general public for their photoprotective
      properties, including prevention of photocarcinogenesis and photoaging and
      management of photodermatoses. It is important to emphasize to consumers the
      necessity of broad-spectrum protection, with coverage of both ultraviolet A (320
      400 nm) and ultraviolet B (290-320 nm) radiation. This review discusses the
      benefits of sunscreen, different ultraviolet filters, sunscreen regulations and
      controversies, the importance of broad-spectrum protection, issues of
      photostability and formulation, and patient education and compliance.

PMID- 28510142
TI  - Local heating of molecular motors using single carbon nanotubes.
AB  - Temperature globally affects all chemical processes and biomolecules in living
      cells. Elevating the temperature of an entire cell accelerates so many
      biomolecular reactions simultaneously that it is difficult to distinguish the
      various mechanisms involved. The ability to localize temperature changes to the
      nanometer range within a cell could provide a powerful new tool for regulating
      biomolecular activity at the level of individual molecules. The search for a
      nanoheater for biological research has prompted experiments with carbon nanotubes
      (CNTs), which have the highest conductivity of any known material. The adsorption
      of skeletal muscle myosin molecules along the length of single multi-walled CNTs
      (~10 MUm) has allowed researchers to observe the ATP-driven sliding of
      fluorescently labeled actin filaments. In one study, red-laser irradiation
      focused on one end of a myosin-coated CNT was used to heat myosin motors locally
      without directly heating the surrounding water; this laser irradiation instantly
      accelerated the actin-filament sliding speeds from ~6 to ~12 MUm/s in a
      reversible manner, indicating a local, real-time heating of myosin motors by
      approximately Delta12 K. Calculation of heat transfer using the finite element
      method, based on the estimated temperature along a single CNT with a diameter of
      170 nm, indicated a high thermal conductivity of ~1540 Wm-1K-1 in solution,
      consistent with values measured in vacuum in earlier studies. Temperature
      distribution indicated by half-decrease distances was ~3660 nm along the length
      of the CNT and ~250 nm perpendicular to the length. These results suggest that
      single-CNT-based heating at the nanometer- or micrometer-range could be used to
      regulate various biomolecules in many areas of biological, physical, and chemical
      research.

PMID- 28510143
TI  - The structural stability and catalytic activity of DNA and RNA oligonucleotides
      in the presence of organic solvents.
AB  - Organic solvents and apolar media are used in the studies of nucleic acids to
      modify the conformation and function of nucleic acids, to improve solubility of
      hydrophobic ligands, to construct molecular scaffolds for organic synthesis, and
      to study molecular crowding effects. Understanding how organic solvents affect
      nucleic acid interactions and identifying the factors that dominate solvent
      effects are important for the creation of oligonucleotide-based technologies.
      This review describes the structural and catalytic properties of DNA and RNA
      oligonucleotides in organic solutions and in aqueous solutions with organic
      cosolvents. There are several possible mechanisms underlying the effects of
      organic solvents on nucleic acid interactions. The reported results emphasize the
      significance of the osmotic pressure effect and the dielectric constant effect in
      addition to specific interactions with nucleic acid strands. This review will
      serve as a guide for the selection of solvent systems based on the purpose of the
      nucleic acid-based experiments.

PMID- 28510144
TI  - Enhanced sampling simulations to construct free-energy landscape of protein
      partner substrate interaction.
AB  - Molecular dynamics (MD) simulations using all-atom and explicit solvent models
      provide valuable information on the detailed behavior of protein-partner
      substrate binding at the atomic level. As the power of computational resources
      increase, MD simulations are being used more widely and easily. However, it is
      still difficult to investigate the thermodynamic properties of protein-partner
      substrate binding and protein folding with conventional MD simulations. Enhanced
      sampling methods have been developed to sample conformations that reflect
      equilibrium conditions in a more efficient manner than conventional MD
      simulations, thereby allowing the construction of accurate free-energy
      landscapes. In this review, we discuss these enhanced sampling methods using a
      series of case-by-case examples. In particular, we review enhanced sampling
      methods conforming to trivial trajectory parallelization, virtual-system coupled
      multicanonical MD, and adaptive lambda square dynamics. These methods have been
      recently developed based on the existing method of multicanonical MD simulation.
      Their applications are reviewed with an emphasis on describing their practical
      implementation. In our concluding remarks we explore extensions of the enhanced
      sampling methods that may allow for even more efficient sampling.

PMID- 28510145
TI  - Isopeptide bond in collagen- and fibrinogen-binding MSCRAMMs.
AB  - The internal isopeptide bonds are amide bonds formed autocatalytically between
      the side chains of Lys and Asn/Asp residues and have been discovered recently.
      These bonds are well conserved in Gram-positive bacterial pilin proteins and are
      also observed over a wide range of Gram-positive bacterial surface proteins. The
      presence of these bonds confers the pilus subunits with remarkable properties in
      terms of thermal stability and resistance to proteases. Like pili, microbial
      surface components recognizing adhesive matrix molecules (MSCRAMMs) are also
      surface proteins found only in Gram-positive bacteria. They specifically interact
      with the extracellular matrix (ECM) molecules like collagen, fibrinogen,
      fibronectin, laminin, etc. Many biophysical and biochemical studies have been
      carried out to characterize the isopeptide bonds in pili proteins from Gram
      positive bacteria, but no attempts have been made to study the isopeptide bonds
      in MSCRAMMs. This short review aims to study the significance of the isopeptide
      bonds in relation to their function, by analyzing the crystal structures of
      collagen- and fibrinogen-binding MSCRAMMs. In this analysis, interestingly, we
      observed that the putative isopeptide bonds are restricted to the collagen
      binding MSCRAMMs. Based on analogy with bacterial pilus subunits, we hypothesize
      that the collagen-binding MSCRAMMs possessing putative isopeptide bonds exhibit
      similar structural properties, which could help the bacteria in colonizing the
      host and provide resistance against host-defense mechanisms.

PMID- 28510147
TI  - The evolution of Biophysical Reviews.

PMID- 28510146
TI  - PWWP domains and their modes of sensing DNA and histone methylated lysines.
AB  - Chromatin plays an important role in gene transcription control, cell cycle
      progression, recombination, DNA replication and repair. The fundamental unit of
      chromatin, the nucleosome, is formed by a DNA duplex wrapped around an octamer of
      histones. Histones are susceptible to various post-translational modifications,
      covalent alterations that change the chromatin status. Lysine methylation is one
      of the major post-translational modifications involved in the regulation of
      chromatin function. The PWWP domain is a member of the Royal superfamily that
      functions as a chromatin methylation reader by recognizing both DNA and histone
      methylated lysines. The PWWP domain three-dimensional structure is based on an N
      terminal hydrophobic beta-barrel responsible for histone methyl-lysine binding,
      and a C-terminal alpha-helical domain. In this review, we set out to discuss the
      most recent literature on PWWP domains, focusing on their structural features and
      the mechanisms by which they specifically recognize DNA and histone methylated
      lysines at the level of the nucleosome.

PMID- 28510148
TI  - Glucose transporters: physiological and pathological roles.
AB  - Glucose is a primary energy source for most cells and an important substrate for
      many biochemical reactions. As glucose is a need of each and every cell of the
      body, so are the glucose transporters. Consequently, all cells express these
      important proteins on their surface. In recent years developments in genetics
      have shed new light on the types and physiology of various glucose transporters,
      of which there are two main types-sodium-glucose linked transporters (SGLTs) and
      facilitated diffusion glucose transporters (GLUT)-which can be divided into many
      more subclasses. Transporters differ in terms of their substrate specificity,
      distribution and regulatory mechanisms. Glucose transporters have also received
      much attention as therapeutic targets for various diseases. In this review, we
      attempt to present a simplified view of this complex topic which may be of
      interest to researchers involved in biochemical and pharmacological research.

PMID- 28510150
TI  - Editorial.

PMID- 28510149
TI  - Structural aspects of nucleic acid-sensing Toll-like receptors.
AB  - Invading pathogens elicit potent immune responses in cells through interactions
      between structurally conserved molecules derived from the pathogens and
      specialized innate immune receptors such as the Toll-like receptors (TLRs).
      Nucleic acid is one of the principal TLR ligands. Nucleic acid-sensing TLRs
      recognize an array of nucleic acids, including double-stranded RNA, single
      stranded RNA, and DNAs with specific sequence motifs. Although ligand-induced
      dimerization is commonly observed followed by TLR activation, both the specific
      recognition mechanisms and the ligand-receptor interactions vary among different
      TLRs. In this review, we highlight our current understanding of how these
      receptors recognize their cognate ligands based on the recent advances in
      structural biology.

PMID- 28510152
TI  - Biochemical characterization of breast tumors by in vivo and in vitro magnetic
      resonance spectroscopy (MRS).
AB  - Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have
      evolved as sensitive tools for anatomic and metabolic evaluation of breast
      cancer. In vivo MRS studies have documented the presence of choline containing
      compounds (tCho) as a reliable biochemical marker of malignancy and also useful
      for monitoring the tumor response to therapy. Recent studies on the absolute
      quantification of tCho are expected to provide cut-off values for discrimination
      of various breast pathologies. Addition of MRS investigation was also reported to
      increase the specificity of MRI. Further, ex vivo and in vitro MRS studies of
      intact tissues and tissue extracts provided several metabolites that were not be
      detected in vivo and provided insight into underlying biochemistry of the disease
      processes. In this review, we present briefly the role of various 1H MRS methods
      used in breast cancer research and their potential in relation to diagnosis,
      monitoring of therapeutic response and metabolism.

PMID- 28510154
TI  - The role of beta-sheets in the structure and assembly of keratins.
AB  - X-ray diffraction, infrared and electron microscope studies of avian and
      reptilian keratins, and of stretched wool and hair, have played a central role in
      the development of models for the beta-conformation in proteins. Both alpha- and
      beta-keratins contain sequences that are predicted to adopt a beta-conformation
      and these are believed to play an important part in the assembly of the filaments
      and in determining their mechanical properties. Interactions between the small
      beta-sheets in keratins provide a simple mechanism through which shape and
      chemical complementarity can mediate the assembly of molecules into highly
      specific structures. Interacting beta-sheets in crystalline proteins are often
      related to one another by diad symmetry and the data available on feather keratin
      suggest that the filament is assembled from dimers in which the beta-sheets are
      related by a perpendicular diad. The most detailed model currently available is
      for feather and reptilian keratin but the presence of related beta-structural
      forms in mammalian keratins is also noted.

PMID- 28510151
TI  - CFTR structure and function: is there a role in the kidney?
AB  - Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by
      mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the
      CFTR gene may result in a defective protein processing that leads to changes in
      function and regulation of this chloride channel. Despite of the expression of
      CFTR in the kidney, patients with CF do not present major renal dysfunction, but
      it is known that both the urinary excretion of proteins and renal capacity to
      concentrate and dilute urine are altered in these patients. CFTR mRNA is
      expressed in all nephron segments of rat and human, and this abundance is more
      prominent in renal cortex and outer medulla renal areas. CFTR protein was
      detected in apical surface of both proximal and distal tubules of rat kidney but
      not in the outer medullary collecting ducts. Studies have demonstrated that CFTR
      does not only transport Cl- but also ATP. ATP transport by CFTR could be involved
      in the control of other ion transporters such as Na+ (ENaC) and K+ (renal outer
      medullary potassium) channels, especially in TAL and CCD. In the kidney, CFTR
      also might be involved in the endocytosis of low-molecular-weight proteins by
      proximal tubules. This review is focused on the CFTR function and structure, its
      role in the renal physiology, and its modulation by hormones involved in the
      control of extracellular fluid volume.

PMID- 28510153
TI  - Intercalated discs: multiple proteins perform multiple functions in non-failing
      and failing human hearts.
AB  - The intercalated disc (ICD) occupies a central position in the transmission of
      force, electrical continuity and chemical communication between cardiomyocytes.
      Changes in its structure and composition are strongly implicated in heart
      failure. ICD functions include: maintenance of electrical continuity across the
      ICD; physical links between membranes and the cytoskeleton; intercellular
      adhesion; maintenance of ICD structure and function; and growth. About 200 known
      proteins are associated with ICDs, 40% of which change in disease. We
      systemically reviewed cardiac immunohistochemical data on the Human Protein Atlas
      (HPA) web site, ExPASy protein binding data and published papers on ICDs. We
      identified 43 proteins not previously reported, and confirmed 37 proteins that
      have previously been described. In addition, 102 proteins not present on the HPA
      web site but were described in ICDs in the literature. We group these into
      clusters that demonstrate functionally interactive groups of proteins
      demonstrating that ICDs play a key role in cardiomyocyte function.

PMID- 28510155
TI  - A historical perspective of the biophysics of the thrombin-heparin system: an
      example of nonspecific binding and the consequent parking problem in action.
AB  - Difficulties are encountered in the thermodynamic characterization of
      interactions between a protein ligand and a linear acceptor, such as a
      polynucleotide or a polysaccharide, because of the involvement of more than one
      unit of the polymer chain in each attachment of a protein molecule. Complications
      arise from the fact that random attachment of ligand to the polymer chain, each
      unit of which is a potential binding site, initially leads to suboptimal location
      of protein molecules along the polymer chain-a situation that has to be rectified
      before the attainment of thermodynamic equilibrium can be realized. Kinetic as
      well as thermodynamic consequences of such nonspecific binding, termed the
      parking problem, therefore need to be considered in any quantitative
      characterization of the interaction between a large ligand and a linear polymer
      acceptor chain. Results for the thrombin-heparin interaction have been used to
      illustrate a thermodynamic characterization of nonspecific binding that takes
      into account these consequences of the parking problem.

PMID- 28510156
TI  - Effects of macromolecular crowding agents on protein folding in vitro and in
      silico.
AB  - Proteins fold and function inside cells which are environments very different
      from that of dilute buffer solutions most often used in traditional experiments.
      The crowded milieu results in excluded-volume effects, increased bulk viscosity
      and amplified chances for inter-molecular interactions. These environmental
      factors have not been accounted for in most mechanistic studies of protein
      folding executed during the last decades. The question thus arises as to how
      these effects-present when polypeptides normally fold in vivo-modulate protein
      biophysics. To address excluded volume effects, we use synthetic macromolecular
      crowding agents, which take up significant volume but do not interact with
      proteins, in combination with strategically selected proteins and a range of
      equilibrium and time-resolved biophysical (spectroscopic and computational)
      methods. In this review, we describe key observations on macromolecular crowding
      effects on protein stability, folding and structure drawn from combined in vitro
      and in silico studies. As expected based on Minton's early predictions, many
      proteins (apoflavodoxin, VlsE, cytochrome c, and S16) became more
      thermodynamically stable (magnitude depends inversely on protein stability in
      buffer) and, unexpectedly, for apoflavodoxin and VlsE, the folded states changed
      both secondary structure content and, for VlsE, overall shape in the presence of
      macromolecular crowding. For apoflavodoxin and cytochrome c, which have complex
      kinetic folding mechanisms, excluded volume effects made the folding energy
      landscapes smoother (i.e., less misfolding and/or kinetic heterogeneity) than in
      buffer.

PMID- 28510157
TI  - Soft interactions and crowding.
AB  - The intracellular milieu is complex, heterogeneous and crowded-an environment
      vastly different from dilute solutions in which most biophysical studies are
      performed. The crowded cytoplasm excludes about a third of the volume available
      to macromolecules in dilute solution. This excluded volume is the sum of two
      parts: steric repulsions and chemical interactions, also called soft
      interactions. Until recently, most efforts to understand crowding have focused on
      steric repulsions. Here, we summarize the results and conclusions from recent
      studies on macromolecular crowding, emphasizing the contribution of soft
      interactions to the equilibrium thermodynamics of protein stability. Despite
      their non-specific and weak nature, the large number of soft interactions present
      under many crowded conditions can sometimes overcome the stabilizing steric,
      excluded volume effect.

PMID- 28510158
TI  - Assessment and significance of protein-protein interactions during development of
      protein biopharmaceuticals.
AB  - Early development of protein biotherapeutics using recombinant DNA technology
      involved progress in the areas of cloning, screening, expression and
      recovery/purification. As the biotechnology industry matured, resulting in
      marketed products, a greater emphasis was placed on development of formulations
      and delivery systems requiring a better understanding of the chemical and
      physical properties of newly developed protein drugs. Biophysical techniques such
      as analytical ultracentrifugation, dynamic and static light scattering, and
      circular dichroism were used to study protein-protein interactions during various
      stages of development of protein therapeutics. These studies included
      investigation of protein self-association in many of the early development
      projects including analysis of highly glycosylated proteins expressed in
      mammalian CHO cell cultures. Assessment of protein-protein interactions during
      development of an IgG1 monoclonal antibody that binds to IgE were important in
      understanding the pharmacokinetics and dosing for this important biotherapeutic
      used to treat severe allergic IgE-mediated asthma. These studies were extended to
      the investigation of monoclonal antibody-antigen interactions in human serum
      using the fluorescent detection system of the analytical ultracentrifuge.
      Analysis by sedimentation velocity analytical ultracentrifugation was also used
      to investigate competitive binding to monoclonal antibody targets. Recent
      development of high concentration protein formulations for subcutaneous
      administration of therapeutics posed challenges, which resulted in the use of
      dynamic and static light scattering, and preparative analytical
      ultracentrifugation to understand the self-association and rheological properties
      of concentrated monoclonal antibody solutions.

PMID- 28510161
TI  - Protein-protein interactions in a crowded environment.
AB  - Protein-protein interactions are important in many essential biological
      functions, such as transcription, translation, and signal transduction. Much
      progress has been made in understanding protein-protein association in dilute
      solution via experimentation and simulation. Cells, however, contain various
      macromolecules, such as DNA, RNA, proteins, among many others, and a myriad of
      non-specific interactions (usually weak) are present between these cellular
      constituents. In this review article, we describe the important developments in
      recent years that have furthered our understanding and even allowed prediction of
      the consequences of macromolecular crowding on protein-protein interactions. We
      outline the development of our crowding theory that can predict the change in
      binding free energy due to crowding quantitatively for both repulsive and
      attractive protein-crowder interactions. One of the most important findings from
      our recent work is that weak attractive interactions between crowders and
      proteins can actually destabilize protein complex formation as opposed to the
      commonly assumed stabilizing effect predicted based on traditional crowding
      theories that only account for the entropic-excluded volume effects. We also
      discuss the implications of macromolecular crowding on the population of
      encounter versus specific native complex.

PMID- 28510159
TI  - The loop hypothesis: contribution of early formed specific non-local interactions
      to the determination of protein folding pathways.
AB  - The extremely fast and efficient folding transition (in seconds) of globular
      proteins led to the search for some unifying principles embedded in the physics
      of the folding polypeptides. Most of the proposed mechanisms highlight the role
      of local interactions that stabilize secondary structure elements or a folding
      nucleus as the starting point of the folding pathways, i.e., a "bottom-up"
      mechanism. Non-local interactions were assumed either to stabilize the nucleus or
      lead to the later steps of coalescence of the secondary structure elements. An
      alternative mechanism was proposed, an "up-down" mechanism in which it was
      assumed that folding starts with the formation of very few non-local interactions
      which form closed long loops at the initiation of folding. The possible
      biological advantage of this mechanism, the "loop hypothesis", is that the
      hydrophobic collapse is associated with ordered compactization which reduces the
      chance for degradation and misfolding. In the present review the experiments,
      simulations and theoretical consideration that either directly or indirectly
      support this mechanism are summarized. It is argued that experiments monitoring
      the time-dependent development of the formation of specifically targeted early
      formed sub-domain structural elements, either long loops or secondary structure
      elements, are necessary. This can be achieved by the time-resolved FRET-based
      "double kinetics" method in combination with mutational studies. Yet, attempts to
      improve the time resolution of the folding initiation should be extended down to
      the sub-microsecond time regime in order to design experiments that would resolve
      the classes of proteins which first fold by local or non-local interactions.

PMID- 28510160
TI  - Macromolecular interactions of the bacterial division FtsZ protein: from
      quantitative biochemistry and crowding to reconstructing minimal divisomes in the
      test tube.
AB  - The division of Escherichia coli is an essential process strictly regulated in
      time and space. It requires the association of FtsZ with other proteins to
      assemble a dynamic ring during septation, forming part of the functionally active
      division machinery, the divisome. FtsZ reversibly interacts with FtsA and ZipA at
      the cytoplasmic membrane to form a proto-ring, the first molecular assembly of
      the divisome, which is ultimately joined by the rest of the division-specific
      proteins. In this review we summarize the quantitative approaches used to study
      the activity, interactions, and assembly properties of FtsZ under well-defined
      solution conditions, with the aim of furthering our understanding of how the
      behavior of FtsZ is controlled by nucleotides and physiological ligands. The
      modulation of the association and assembly properties of FtsZ by excluded-volume
      effects, reproducing in part the natural crowded environment in which this
      protein has evolved to function, will be described. The subsequent studies on the
      reactivity of FtsZ in membrane-like systems using biochemical, biophysical, and
      imaging technologies are reported. Finally, we discuss the experimental
      challenges to be met to achieve construction of the minimum protein set needed to
      initiate bacterial division, without cells, in a cell-like compartment. This
      integrated approach, combining quantitative and synthetic strategies, will help
      to support (or dismiss) conclusions already derived from cellular and molecular
      analysis and to complete our understanding on how bacterial division works.

PMID- 28510162
TI  - Foreword to the biophysics of protein-protein and protein-ligand interactions in
      dilute and crowded media-a special issue in honor of Allen Minton's 70th
      birthday.

PMID- 28510163
TI  - Ratchets, red cells, and metastability.
AB  - Sickle cell disease is a genetic disorder in which a negatively charged glutamic
      acid is replaced by a hydrophobic valine on the surface of the hemoglobin
      molecule, leading to polymerization of the deoxygenated form, and resulting in
      microvascular obstruction. Because of the high volume occupancy under which
      polymerization occurs physiologically, this process has been an exemplar in the
      study of excluded volume effects on assembly. More recently, we have identified
      yet another type of crowding effect involving the obstruction of the ends at
      which the polymers grow as a consequence of the dense arrays in which these
      polymers form. This makes such solutions metastable, and leads to Brownian
      ratchet behavior in which pressure is exerted outward when the gel occupies a
      finite volume, as in an emulsion or red cell. Such behavior is capable of holding
      sickled cells in place in the microcirculation against weak pressure
      differentials (hundreds of Pa), but not against the typical pressures found in
      vivo.

PMID- 28510164
TI  - Entropic stabilization of the folded states of RNA due to macromolecular
      crowding.
AB  - We review the effects of macromolecular crowding on the folding of RNA by
      considering the simplest scenario when excluded volume interactions between
      crowding particles and RNA dominate. Using human telomerase enzyme as an example,
      we discuss how crowding can alter the equilibrium between pseudoknot and hairpin
      states of the same RNA molecule-a key aspect of crowder-RNA interactions. We
      summarize data showing that the crowding effect is significant only if the size
      of the spherical crowding particle is smaller than the radius of gyration of the
      RNA in the absence of crowding particles. The implication for function of the
      wild type and mutants of human telomerase is outlined by using a relationship
      between enzyme activity and its conformational equilibrium. In addition, we
      discuss the interplay between macromolecular crowding and ionic strength of the
      RNA buffer. Finally, we briefly review recent experiments which illustrate the
      connection between excluded volume due to macromolecular crowding and the
      thermodynamics of RNA folding.

PMID- 28510166
TI  - A brief look back at 45 years of research in physical biochemistry.

PMID- 28510167
TI  - Note on "Protein dynamics and the allosteric transitions of pentameric receptor
      channels" by Jean-Pierre Changeux.

PMID- 28510165
TI  - Protein interactions in the assembly of the tail of bacteriophage T4.
AB  - Protein interactions in the assembly of the baseplate have been investigated. The
      baseplate of the phage T4 tail consists of a hub and six wedges which surround
      the former. Both reversible and irreversible interactions were found. Reversible
      association includes gp5 and gp27 (gp: gene product) which form a complex in a pH
      dependent manner and gp18 polymerization, i.e. the tail sheath formation depends
      on the ionic strength. These reversible interactions were followed by
      irreversible or tight binding which pulls the whole association reaction to
      complete the assembly. The wedge assembly is strictly ordered which means that if
      one of the seven wedge proteins is missing, the assembly proceeds to that point
      and the remaining molecules stay non-associated. The strictly sequential assembly
      pathway is suggested to be materialized by successive conformational change upon
      binding, which can be shown by proteolytic probe.

PMID- 28510168
TI  - Nanoscale protein domain motion and long-range allostery in signaling proteins-a
      view from neutron spin echo spectroscopy.
AB  - Many cellular proteins are multi-domain proteins. Coupled domain-domain
      interactions in these multidomain proteins are important for the allosteric relay
      of signals in the cellular signaling networks. We have initiated the application
      of neutron spin echo spectroscopy to the study of nanoscale protein domain
      motions on submicrosecond time scales and on nanometer length scale. Our NSE
      experiments reveal the activation of protein domain motions over a long distance
      of over more than 100 A in a multidomain scaffolding protein NHERF1 upon binding
      to another protein, Ezrin. Such activation of nanoscale protein domain motions is
      correlated with the allosteric assembly of multi-protein complexes by NHERF1 and
      Ezrin. Here, we summarize the theoretical framework that we have developed, which
      uses simple concepts from nonequilibrium statistical mechanics to interpret the
      NSE data, and employs a mobility tensor to describe nanoscale protein domain
      motion. Extracting nanoscale protein domain motion from the NSE does not require
      elaborate molecular dynamics simulations, nor complex fits to rotational motion,
      nor elastic network models. The approach is thus more robust than multiparameter
      techniques that require untestable assumptions. We also demonstrate that an
      experimental scheme of selective deuteration of a protein subunit in a complex
      can highlight and amplify specific domain dynamics from the abundant global
      translational and rotational motions in a protein. We expect NSE to provide a
      unique tool to determine nanoscale protein dynamics for the understanding of
      protein functions, such as how signals are propagated in a protein over a long
      distance to a distal domain.

PMID- 28510169
TI  - Global low-frequency motions in protein allostery: CAP as a model system.
AB  - Allostery is a fundamental process by which ligand binding to a protein alters
      its activity at a distant site. There is considerable evidence that allosteric
      cooperativity can be communicated by the modulation of protein dynamics without
      conformational change. The Catabolite Activator Protein (CAP) of Escherichia coli
      is an important experimental exemplar for entropically driven allostery. Here we
      discuss recent experimentally supported theoretical analysis that highlights the
      role of global low-frequency dynamics in allostery in CAP and identify how
      allostery arises as a natural consequence of changes in global low-frequency
      protein fluctuations on ligand binding.

PMID- 28510170
TI  - Relaxation dispersion NMR spectroscopy for the study of protein allostery.
AB  - Allosteric transmission of information between distant sites in biological
      macromolecules often involves collective transitions between active and inactive
      conformations. Nuclear magnetic resonance (NMR) spectroscopy can yield detailed
      information on these dynamics. In particular, relaxation dispersion techniques
      provide structural, dynamic, and mechanistic information on conformational
      transitions occurring on the millisecond to microsecond timescales. In this
      review, we provide an overview of the theory and analysis of Carr-Purcell-Meiboom
      Gill (CPMG) relaxation dispersion NMR experiments and briefly describe their
      application to the study of allosteric dynamics in the homeodomain from the PBX
      transcription factor (PBX-HD). CPMG NMR data show that local folding (helix/coil)
      transitions in one part of PBX-HD help to communicate information between two
      distant binding sites. Furthermore, the combination of CPMG and other spin
      relaxation data show that this region can also undergo local misfolding,
      reminiscent of conformational ensemble models of allostery.

PMID- 28510171
TI  - Terahertz optical measurements of correlated motions with possible allosteric
      function.
AB  - A suggested mechanism for allosteric response is the distortion of the energy
      landscape with agonist binding changing the protein structure's access to
      functional configurations. Intramolecular vibrations are indicative of the energy
      landscape and may have trajectories that enable functional conformational change.
      Here, we discuss the development of an optical method to measure the
      intramolecular vibrations in proteins, namely, crystal anisotropy terahertz
      microscopy, and the various approaches which can be used to identify the spectral
      data with specific structural motions.

PMID- 28510172
TI  - Contrasting roles of dynamics in protein allostery: NMR and structural studies of
      CheY and the third PDZ domain from PSD-95.
AB  - Allosteric regulation is a ubiquitous phenomenon exploited in biological
      processes to control cells in a myriad of ways. It is also of emerging interest
      in the design of functional proteins and therapeutics. Even though allostery was
      proposed over 50 years ago and has been studied intensively from a structural
      perspective, many key details of allosteric mechanisms remain mysterious. Over
      the last decade significant attention has been paid to the "dynamic component" of
      allostery, as opposed to the analysis of rigid structures. Nuclear magnetic
      resonance spectroscopy and its ability to detect conformationally dynamic
      processes at atomic resolution have played an important role in expanding our
      understanding of allosteric mechanisms and opening up new questions. This article
      focuses on work that highlights how protein dynamics can factor into allosteric
      processes in distinct ways. Two cases are contrasted. The first considers the
      "traditionally allosteric" protein CheY, which undergoes a conformational change
      as a key element of its allostery. The second considers the more rarely observed
      "dynamic allostery" in a PDZ domain, in which allosteric behavior arises from
      changes in internal structural dynamics. Interestingly, the dynamic processes in
      these two contrasting examples occur on different timescales. In the case of the
      PDZ domain, subsequent experimental and computational work is reviewed to reveal
      a more complete picture of this interesting case of allostery.

PMID- 28510173
TI  - Disordered allostery: lessons from glucocorticoid receptor.
AB  - Allostery is a biological regulation mechanism of significant importance in cell
      signaling, metabolism, and disease. Although the ensemble basis of allostery has
      been known for years, only recently has emphasis shifted from interpreting
      allosteric mechanism in terms of discrete structural pathways to ones that focus
      on the statistical nature of the signal propagation process, providing a vehicle
      to unify allostery in structured, dynamic, and disordered systems. In particular,
      intrinsically disordered (ID) proteins (IDPs), which lack a unique, stable
      structure, have been directly demonstrated to exhibit allostery in numerous
      systems, a reality that challenges traditional structure-based models that focus
      on allosteric pathways. In this chapter, we will discuss the historical context
      of allostery and focus on studies from human glucocorticoid receptor (GR), a
      member of the steroid hormone receptor (SHR) family. The numerous translational
      isoforms of the disordered N-terminal domain of GR consist of coupled
      thermodynamic domains that contribute to the delicate balance of states in the
      ensemble and hence in vivo activity. The data are quantitatively interpreted
      using the ensemble allosteric model (EAM) that considers only the intrinsic and
      measurable energetics of allosteric systems. It is demonstrated that the EAM
      provides mechanistic insight into the distribution of states in solution and
      provides an interpretation for how certain translational isoforms of GR display
      enhanced and repressed transcriptional activities. The ensemble nature of
      allostery illuminated from these studies lends credence to the EAM and provides
      ground rules for allostery in all systems.

PMID- 28510174
TI  - The role of slow and fast protein motions in allosteric interactions.
AB  - Allostery is fundamentally thermodynamic in nature. Long-range communication in
      proteins may be mediated not only by changes in the mean conformation with
      enthalpic contribution but also by changes in dynamic fluctuations with entropic
      contribution. The important role of protein motions in mediating allosteric
      interactions has been established by NMR spectroscopy. By using CAP as a model
      system, we have shown how changes in protein structure and internal dynamics can
      allosterically regulate protein function and activity. The results indicate that
      changes in conformational entropy can give rise to binding enhancement, binding
      inhibition, or have no effect in the expected affinity, depending on the
      magnitude and sign of enthalpy-entropy compensation. Moreover, allosteric
      interactions can be regulated by the modulation a low-populated conformation
      states that serve as on-pathway intermediates for ligand binding. Taken together,
      the interplay between fast internal motions, which are intimately related to
      conformational entropy, and slow internal motions, which are related to poorly
      populated conformational states, can regulate protein activity in a way that
      cannot be predicted on the basis of the protein's ground-state structure.

PMID- 28510175
TI  - The role of protein dynamics in allosteric effects-introduction.

PMID- 28510176
TI  - Molecular mechanisms of acetylcholine receptor-lipid interactions: from model
      membranes to human biology.
AB  - Lipids are potent modulators of the Torpedo nicotinic acetylcholine receptor.
      Lipids influence nicotinic receptor function by allosteric mechanisms,
      stabilizing varying proportions of pre-existing resting, open, desensitized, and
      uncoupled conformations. Recent structures reveal that lipids could alter
      function by modulating transmembrane alpha-helix/alpha-helix packing, which in
      turn could alter the conformation of the allosteric interface that links the
      agonist-binding and transmembrane pore domains-this interface is essential in the
      coupling of agonist binding to channel gating. We discuss potential mechanisms by
      which lipids stabilize different conformational states in the context of the
      hypothesis that lipid-nicotinic receptor interactions modulate receptor function
      at biological synapses.

PMID- 28510177
TI  - Review of biophysical factors affecting osteogenic differentiation of human adult
      adipose-derived stem cells.
AB  - Developing bone is subject to the control of a broad variety of influences in
      vivo. For bone repair applications, in vitro osteogenic assays are routinely used
      to test the responses of bone-forming cells to drugs, hormones, and biomaterials.
      Results of these assays are used to predict the behavior of bone-forming cells in
      vivo. Stem cell research has shown promise for enhancing bone repair. In vitro
      osteogenic assays to test the bone-forming response of stem cells typically use
      chemical solutions. Stem cell in vitro osteogenic assays often neglect important
      biophysical cues, such as the forces associated with regular weight-bearing
      exercise, which promote bone formation. Incorporating more biophysical cues that
      promote bone formation would improve in vitro osteogenic assays for stem cells.
      Improved in vitro osteogenic stimulation opens opportunities for "pre
      conditioning" cells to differentiate towards the desired lineage. In this review,
      we explore the role of select biophysical factors-growth surfaces, tensile
      strain, fluid flow and electromagnetic stimulation-in promoting osteogenic
      differentiation of stem cells from human adipose. Emphasis is placed on the
      potential for physical microenvironment manipulation to translate tissue
      engineering and stem cell research into widespread clinical usage.

PMID- 28510179
TI  - Design and operation of an automated high-throughput monoclonal antibody
      facility.
AB  - Monoclonal antibodies now form a key part of the biochemist's toolbox, and are
      important reagents for therapeutic applications. This has resulted in a need for
      high-throughput production to satisfy the demand from the global community.
      Manual production involves overwhelming amounts of tissue culture and associated
      liquid handling steps to achieve high-throughput operation. By contrast,
      automated systems can readily cope with the numbers required. In this review, we
      address the development of automated systems, and discuss the pros and cons of
      their operation.

PMID- 28510178
TI  - SH3 domains: modules of protein-protein interactions.
AB  - Src homology 3 (SH3) domains are involved in the regulation of important cellular
      pathways, such as cell proliferation, migration and cytoskeletal modifications.
      Recognition of polyproline and a number of noncanonical sequences by SH3 domains
      has been extensively studied by crystallography, nuclear magnetic resonance and
      other methods. High-affinity peptides that bind SH3 domains are used in drug
      development as candidates for anticancer treatment. This review summarizes the
      latest achievements in deciphering structural determinants of SH3 function.

PMID- 28510182
TI  - Metal ion-dependent anti-termination of transcriptional regulation of
      ribonucleoprotein complexes.
AB  - Anti-terminator proteins are frequently used by bacteria to sense a specific
      metabolite signal and direct RNA polymerase to either terminate or continue
      transcription of the genes downstream of an operon. One such protein is HutP,
      which binds to upstream cis-regulatory sequences to regulate expression of the
      histidine utilization (hut) operon in Bacillus subtilis. HutP must be activated
      by L-histidine and divalent metal ions before binding to hut mRNA; binding of
      activated HutP prevents termination of transcription. Thus, HutP appears to
      regulate the hut operon in a unique fashion in this class of regulatory proteins.
      To understand gene (hut operon) regulation by HutP, we performed several
      biochemical and structural studies. These studies reveal events in the regulatory
      mechanism, starting with the activation of HutP and ending with the unwinding of
      hut terminator RNA. In this review, we describe the unique regulatory mechanisms
      commonly used by many Bacillus species.

PMID- 28510180
TI  - Structural and mechanical functions of integrins.
AB  - Integrins are ubiquitously expressed cell surface receptors that play a critical
      role in regulating the interaction between a cell and its microenvironment to
      control cell fate. These molecules are regulated either via their expression on
      the cell surface or through a unique bidirectional signalling mechanism. However,
      integrins are just the tip of the adhesome iceberg, initiating the assembly of a
      large range of adaptor and signalling proteins that mediate the structural and
      signalling functions of integrin. In this review, we summarise the structure of
      integrins and mechanisms by which integrin activation is controlled. The
      different adhesion structures formed by integrins are discussed, as well as the
      mechanical and structural roles integrins play during cell migration. As the
      function of integrin signalling can be quite varied based on cell type and
      context, an in depth understanding of these processes will aid our understanding
      of aberrant adhesion and migration, which is often associated with human
      pathologies such as cancer.

PMID- 28510184
TI  - Footprint of the eastern euroasian past in Italian populations of Cryptotaenia
      thomasii (Ten.) DC.
AB  - BACKGROUND: The knowledge of the genetic architecture of closely related species
      and/or populations of a single species can be very useful to shed light on the
      processes that led to their current distributions. The present study provides a
      preliminary evaluation of the conservation status of the populations of
      Cryptotaenia thomasii, a very narrow endemic species occurring in southern Italy.
      Previous studies showed that C. thomasii was phylogenetically closely related to
      C. flahaultii, endemic species of Caucasus, and to evaluate its conservation
      status and the genetic variability of plant species the internal transcribed
      spacers (ITSs) of nuclear ribosomal DNA were sequenced and the SNPs were
      analyzed. RESULTS: The restriction analysis of nrDNA with the restriction enzymes
      allowed to detect the presence of two single mutations (SNPs) among the sequences
      of two species. Our molecular analysis pointed out that C. thomasii and C.
      flahaultii, in spite of their geographical disjunction, show a sign of an ancient
      contact as an extreme case of geographical disjunction Italian-Caucasus.
      CONCLUSION: From the evolutionary history of the species and its distribution
      pattern one can reconstruct a possible scenario with some hypotheses that explain
      the hypothetical ancestral area where the two species were in contact. We
      speculate the two species may have originated from fragmentation of a common
      ancestor widespread in the Western Palearctic zone and have survived in two
      separated refuge areas limited by important mountain systems. This hypothesis is
      supported by our molecular analysis, in fact, the analysis of SNPs showed that
      some C. thomasii populations retain the signs of an ancient link with C.
      flahaultii.

PMID- 28510181
TI  - Integrins in development and cancer.
AB  - The correct control of cell fate decisions is critical for metazoan development
      and tissue homeostasis. It is established that the integrin family of cell
      surface receptors regulate cell fate by mediating cell-cell and cell
      extracellular matrix (ECM) interactions. However, our understanding of how the
      different family members control discrete aspects of cell biology, and how this
      varies between tissues and is temporally regulated, is still in its infancy. An
      emerging area of investigation aims to understand how integrins translate changes
      in tension in the surrounding microenvironment into biological responses. This is
      particularly pertinent due to changes in the mechanical properties of the ECM
      having been linked to diseases, such as cancer. In this review, we provide an
      overview of the roles integrins play in important developmental processes, such
      as proliferation, polarity, apoptosis, differentiation and maintenance of
      "stemness". We also discuss recent advances in integrin mechanobiology and
      highlight the involvement of integrins and aberrant ECM in cancer.

PMID- 28510183
TI  - CFTR and TNR-CFTR expression and function in the kidney.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly
      expressed in the kidney. CFTR mRNA is detected in all nephron segments of rats
      and humans and its expression is higher in the renal cortex and outer medulla
      than in the inner medulla. CFTR protein is detected at the apical surface of both
      proximal and distal tubules of rat kidney but not in the outer medullary
      collecting ducts. The localization of CFTR in the proximal tubules is compatible
      with that of endosomes, suggesting that CFTR might regulate pH in endocytic
      vesicles by equilibrating H+ accumulation due to H+-ATPase activity. Many studies
      have also demonstrated that CFTR also regulates channel pore opening and the
      transport of sodium, chloride and potassium. The kidneys also express a CFTR
      splicing variant, called TNR-CFTR, in a tissue-specific manner, primarily in the
      renal medulla. This splicing variant conserves the functional characteristics of
      wild-type CFTR. The functional significance of TNR-CFTR remains to be elucidated,
      but our group proposes that TNR-CFTR may have a basic function in intracellular
      organelles, rather than in the plasma membrane. Also, this splicing variant is
      able to partially substitute CFTR functions in the renal medulla of Cftr-/- mice
      and CF patients. In this review we discuss the major functions that have been
      proposed for CFTR and TNR-CFTR in the kidney.

PMID- 28510186
TI  - Broomcorn and foxtail millet were cultivated in Taiwan about 5000 years ago.
AB  - BACKGROUND: Archaeobotanical remains of millet were found at the Nan-kuan-li East
      site in Tainan Science Park, southern Taiwan. This site, dated around 5000-4300
      BP, is characterized by remains of the Tapenkeng culture, the earliest Neolithic
      culture found so far in Taiwan. A large number of millet-like carbonized and
      charred seeds with varied sizes and shapes were unearthed from the site by the
      flotation method. Since no millet grain was ever found archaeologically in Taiwan
      previously, this discovery is of great importance and significance. This paper is
      in an attempt to further analyze these plant remains for a clearer understanding
      of the agricultural practice of the ancient inhabitants of the Nan-kuan-li East
      site. RESULT: We used light and scanning electron microscopy to examine the
      morphological features of some modern domesticated and unearthed seeds to compare
      and identify the archaeobotanical remains by three criteria: caryopsis shape,
      embryo notch, and morphology of lemma and palea. We also developed a new
      methodology for distinguishing the excavated foxtail and broomcorn millet seeds.
      CONCLUSION: Two domesticated millet, including broomcorn millet (Panicum
      miliaceum) and foxtail millet (Setaria italica), as well as one wild millet
      species, yellow foxtail (Setaria glauca), were identified in the unearthed seeds.
      Together with the millet remains, rice was also cultivated in the area.
      Archaeological evidence shows that millet and rice farming may have been
      important food sources for people living about 5000 years ago in southern Taiwan.

PMID- 28510185
TI  - Morphological, physiological, cytological and phytochemical studies in diploid
      and colchicine-induced tetraploid plants of Fagopyrum tataricum (L.) Gaertn.
AB  - BACKGROUND: Tartary buckwheat are very popular as an important functional food
      material and its cultivation is very widespread in our whole world, but there
      obviously lack works in the researches of genetic breeding for agricultural and
      medicinal utilization. The aim of this study is to obtain good germplasm
      resources for agricultural and medicinal use of tartary buckwheat (Fagopyrum
      tataricum) by inducing the tetraploid plants. RESULTS: Four cultivars of F.
      tataricum, that is, Qianwei 2#, Jinku 2#, Chuanqiao 1#, and Liuqiao 1# were
      selected to experiment. The tips of seedlings with two true leaves were treated
      by 0.25% (w/v) colchicine solution for 48, 72, and 96 h, respectively. The
      chromosome number of treated plants was determined by metaphase chromosome
      counting of root tip cells and PMCs (pollen mother cells) meiosis observation.
      Tetraploid induction successfully occurred in all three treatments with an
      efficiency ranging from 12.13 to 54.55%. The chromosome number of the diploid
      plants was 2n = 2x = 16, and that of the induced tetraploid plants was 2n = 4x =
      32. The typical morphological and physiological qualities were compared between
      the control diploid and corresponding induced tetraploid plants. Results showed
      that the induced tetraploid plants had obviously larger leaves, flowers, and
      seeds. Moreover, the content of seed protein and flavonoid were also increased in
      the tetraploid plants. The pollen diameter and capsule size of diploid plants
      were significantly smaller than those of tetraploid plants. CONCLUSION: Fagopyrum
      tataricum can be effectively induced into tetraploids by colchicines. The
      tetraploid induction can produce valuable germplasm resources for breeding and is
      a practicable breeding way in F. tataricum.

PMID- 28510187
TI  - Identification and trichothecene genotypes of Fusarium graminearum species
      complex from wheat in Taiwan.
AB  - BACKGROUND: Fusarium head blight (FHB) of wheat caused by Fusarium graminearum
      species complex (FGSC) is a devastating disease worldwide. The pathogens not only
      reduce the yield of wheat, but also impact the quality of wheat by contamination
      with trichothecene mycotoxins. A systematic investigation on the pathogens of FHB
      in Taiwan is lacking. Here, molecular and morphological approaches were used to
      identify species of the Taiwanese FGSC isolates and determine their trichothecene
      genotypes. RESULTS: In this study, a total of 195 isolates of FGSC from diseased
      wheat were collected from 8 areas of northern and central Taiwan. All isolates
      were subjected to seedling inoculation for verification of pathogenicity. The
      pathogenic isolates were genetically characterized by sequence characterized
      amplified region (SCAR), PCR- restriction fragment length polymorphism (RFLP),
      phylogenetic analysis and fixed nucleotides to clarify their phylogenetic
      species, and by PCR assays of TRI genes to determine trichothecene genotypes.
      They were identified as F. asiaticum, F. graminearum sensu stricto, F.
      meridionale and an unknown species. Isolates of F. asiaticum were the major
      causal agents (98%) in this investigated population and were comprised of SCAR
      type 5 (75%), SCAR type 4 (21%) and SCAR type 3 (2%). Their trichothecene
      genotypes were either 15-acetyl-deoxynivalenol (15-ADON) (83%) or nivalenol (NIV)
      genotype (17%). These genetic characterizations indicated that F. asiaticum (15
      ADON SCAR type 5) accounts for 60% of this Taiwanese population. Virulence assay
      on wheat heads indicated virulence of F. asiaticum isolates in subpopulations
      divided by SCAR types or trichothecene genotypes were comparable, suggesting
      other factors influence the unequal subpopulation sizes. CONCLUSIONS: This is the
      first study that FGSC isolates in Taiwan were systematically collected and
      characterized. In addition to F. graminearum sensu stricto and F. meridionale, F.
      asiaticum with 15-ADON genotype was identified as the predominate species in
      Taiwan. In contrast to Chinese and Japanese populations that F. asiaticum
      isolates were typically of 3-ADON or NIV genotype, the predominate 15-ADON
      genotype in Taiwanese population was unique among F. asiaticum populations and
      represented the southernmost 15-ADON genotype population in East Asia.

PMID- 28510188
TI  - Mitigation of salt stress in white clover (Trifolium repens) by Azospirillum
      brasilense and its inoculation effect.
AB  - BACKGROUND: Salinity is one of the increasingly serious environmental problems
      worldwide for cultivating agricultural crops. The present study was aimed to
      ascertain the potential of beneficial soil bacterium Azospirillum brasilense to
      alleviate saline stress in Trifolium repens. Experimental plants (white clover)
      were grown from seeds and inoculated with or without A. brasilense bacterial
      strain supplemented with 0, 40, 80, or 120 mM NaCl into soil. RESULTS: The growth
      attributes including, shoot heights, root lengths, fresh and dry weights, leaf
      area and chlorophyll content were significantly enhanced in T. repens plants
      grown in A. brasilense inoculated soil than un-inoculated controls, particularly
      under elevated salinity conditions (40, 80 and 120 mM NaCl). Malondialdehyde
      content of leaf was recorded to be declined under saline conditions. Moreover,
      the K+/Na+ ratio was also improved in bacterium-inoculated plants, since A.
      brasilense significantly reduced the root and shoot Na+ level under high salty
      environment. CONCLUSIONS: Results revealed that soil inoculation with A.
      brasilense could significantly promote T. repens growth under both non-saline and
      saline environments, and this study might be extended to other vegetables and
      crops for the germination and growth enhancement.

PMID- 28510190
TI  - Chilling susceptibility in mungbean varieties is associated with their
      differentially expressed genes.
AB  - BACKGROUND: Mungbean (Vigna radiata L. Wilczek) is an economically important
      legume of high nutritional value, however, its cultivation is limited by
      susceptibility to chilling. Varieties NM94 and VC1973A, with differential
      susceptibility to stress, serve as good materials for uncovering how they differ
      in chilling tolerance. This study aimed to identify the ultrastructural,
      physiological and molecular changes to provide new insights on the differential
      susceptibility to chilling between varieties VC1973A and NM94. RESULTS: Chilling
      stress caused a greater reduction in relative growth rate, a more significant
      decrease in maximum photochemical efficiency of PSII and DPPH scavenging activity
      and more-pronounced ultrastructural changes in VC1973A than in NM94 seedlings.
      Comparative analyses of transcriptional profiles in NM94 and VC1973A revealed
      that the higher expression of chilling regulated genes (CORs) in NM94. The
      transcript levels of lipid transfer protein (LTP), dehydrin (DHN) and plant
      defensin (PDF) in NM94 seedlings after 72 h at 4  degrees C was higher than that
      in its parental lines VC1973A, 6601 and VC2768A. CONCLUSIONS: Our results
      suggested that LTP, DHN and PDF may mediate chilling tolerance in NM94 seedlings.

PMID- 28510189
TI  - Multiple regulatory roles of AP2/ERF transcription factor in angiosperm.
AB  - APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) is a
      superfamily in plant kingdom, which has been reported to be involved in
      regulation of plant growth and development, fruit ripening, defense response, and
      metabolism. As the final response gene in ethylene signaling pathway, AP2/ERF TF
      could feedback modulate phytohormone biosynthesis, including ethylene, cytokinin,
      gibberellin, and abscisic acid. Moreover, AP2/ERF TF also participates in
      response to the signals of auxin, cytokinin, abscisic acid, and jasmonate. Thus,
      this superfamily is key regulator for connecting the phytohormonal signals. In
      this review, based on the evidence of structural and functional studies, we
      discussed the multiple regulator roles of AP2/ERF TF in angiosperm, and then
      constructed the network model of AP2/ERF TF in response to various phytohormonal
      signals and regulatory mechanism of the cross-talk.

PMID- 28510192
TI  - Phellinus noxius: molecular diversity among isolates from Taiwan and its
      phylogenetic relationship with other species of Phellinus based on sequences of
      the ITS region.
AB  - BACKGROUND: Analysis of phylogenetic relationship of 91 isolates of Phellinus
      noxius obtained from 46 plant species in Taiwan did not show distinct grouping
      based on ITS sequences. RESULTS: However, the ITS nucleotides showed 20 different
      kinds of variations including single nucleotide polymorphisms, deletion and
      insertion in ITS1 and ITS2, but none in 5.8 S. The Taiwanese isolates of P.
      noxius were dividable into long (type L), median (type M) and short (type S)
      groups based on ITS sequence length. Two isolates with identical ITS sequence
      belonged to types L. Type M with 72 isolates was further divided into 33
      subtypes, while types S with 17 isolates was further divided into two subtypes.
      CONCLUSION: Phylogenetic analysis of ITS sequences among Phellinus species showed
      that isolates of P. noxius were in the same clade distinctly separated from other
      Phellinus species.

PMID- 28510191
TI  - Taxonomy of Cyrtochilum-alliance (Orchidaceae) in the light of molecular and
      morphological data.
AB  - BACKGROUND: The generic separateness and specific composition of the orchid genus
      Cyrtochilum was discussed for almost two centuries. Over the years several
      smaller taxa were segregated from this taxon, but their separateness was recently
      questioned based on molecular studies outcomes. The aim of our study was to
      revise concepts of morphological-based generic delimitation in Cyrtochilum
      alliance and to compare it with the results of genetic analysis. We used
      phylogenetic framework in combination with phenetical analysis to provide
      proposal of the generic delimitation within Cyrtochilum-alliance. Two molecular
      markers, ITS and matK were used to construct phylogenetic tree. A total of over
      5000 herbarium specimens were included in the morphological examination and the
      phenetical analysis included 29 generative and vegetative characters. RESULTS:
      Comparative morphology of the previously recognized genera: Buesiella,
      Dasyglossum, Neodryas, Rusbyella, Siederella and Trigonochilum is presented. A
      new species within the the latter genus is described. Fourteen new combinations
      are proposed. The key to the identification of the genera of the Cyrtochilum
      alliance and morphological characteristics of each genus are provided.
      CONCLUSIONS: A total of six separated genera are recognized within Cyrtochilum
      alliance. The reasons of the incompatibility between morphological differences
      observed within studied taxa and phylogenetic tree are argued and the taxonomic
      implications of such inconsistency, resulting in fragmentation or lumping of
      taxonomic units, are discussed.

PMID- 28510193
TI  - Characterization of LhSorP5CS, a gene catalyzing proline synthesis in Oriental
      hybrid lily Sorbonne: molecular modelling and expression analysis.
AB  - BACKGROUND: Abiotic stresses negatively affect plant growth and flower
      production. In plants, P5CS proteins are key enzymes that catalyzed the rate
      limiting steps of proline synthesis, and proline is a well-known osmoprotectant
      that is closely related to abiotic stress tolerance. However, information about
      the P5CS genes, their effects on proline accumulation, and their role in abiotic
      stress tolerance in Lilium is still lacking. RESULTS: We isolated and
      characterized a novel gene (LhSorP5CS) from Oriental hybrid lily cultivar
      Sorbonne. Phylogenetic analysis indicated that LhSorP5CS is a member of the P5CS
      family. The three-dimensional structure of LhSorP5CS predicted by homology
      modeling showed high similarity to its correspondant human P5CS template. Further
      gene expression analysis revealed that LhSorP5CS expression was up-regulated by
      NaCl, mannitol, and ABA, and that stress-exposed plants accumulated proline at a
      significantly higher level than in the control. CONCLUSIONS: LhSorP5CS
      characterized in this study is involved in proline synthesis in lily, and that it
      might play an important role in abiotic stress tolerance. However, there should
      be other P5CS homologues in the lily genome, and some of them could be highly
      stress-induced and more important for proline accumulation. Future studies on
      P5CS family genes would be of great importance to proline-related stress
      tolerance in lily.

PMID- 28510194
TI  - Molecular recircumscription of Broussonetia (Moraceae) and the identity and
      taxonomic status of B. kaempferi var. australis.
AB  - BACKGROUND: Despite being a relatively small genus, the taxonomy of the paper
      mulberry genus Broussonetia remains problematic. Much of the controversy is
      related to the identity and taxonomic status of Broussonetia kaempferi var.
      australis, a name treated as a synonym in the floras of Taiwan and yet accepted
      in the floras of China. At the generic level, the monophyly of Corner (Gard Bull
      Singap 19:187-252, 1962)'s concept of Broussonetia has not been tested. In recent
      studies of Broussonetia of Japan, lectotypes of the genus were designated and
      three species (B. kaempferi, Broussonetia monoica, and Broussonetia papyrifera)
      and a hybrid (B. *kazinoki) were recognized. Based on the revision and molecular
      phylogenetic analyses, this article aims to clarify these issues. RESULTS:
      Herbarium studies, field work, and molecular phylogenetic analyses indicate that
      all Taiwanese materials identifiable to B. kaempferi var. australis are
      conspecific with B. monoica of Japan and China. Molecular phylogenetic analyses
      showed that Broussonetia sensu Corner (Gard Bull Singap 19:187-252, 1962)
      contains two clades corresponding to sect. Broussonetia and sect. Allaeanthus,
      with Malaisia scandens sister to sect. Broussonetia. CONCLUSIONS: Based on our
      analyses, B. kaempferi var. australis is treated as a synonym of B. monoica and
      that B. kaempferi is not distributed in Taiwan. To correct the non-monophyly of
      Broussonetia sensu Corner (Gard Bull Singap 19:187-252, 1962), Broussonetia is
      recircumscribed to contain only sect. Broussonetia and the generic status of
      Allaeanthus is reinstated.

PMID- 28510195
TI  - Meso- or xeromorphic? Foliar characters of Asteraceae in a xeric scrub of Mexico.
AB  - BACKGROUND: The anatomical traits associated with water deficit are also observed
      in plants growing in poor soils. The species may resist water deficit through
      three main strategies: escape, avoid or tolerate. The Pedregal de San Angel
      Ecological Reserve (REPSA), Mexico, is an environment with low nutrient soil and
      low water availability. It is set on the basalt formation derived from the Xitle
      volcano eruption. The main vegetation type is characterized as xerophytic shrub.
      Thus we expect that species growing in this community will show leaf xeromorphic
      traits and may have any of the three response strategies. We analyzed the foliar
      anatomy of 52 species of the Asteraceae family at the REPSA because it is the
      most abundant angiosperm family in the site, showing a wide variety of growth
      forms and anatomical variation. RESULTS: The foliar anatomies of the studied
      Asteraceae were highly variable as well as their quantitative traits as revealed
      by principal component analysis. This agrees with previous studies that found
      great anatomical variation within the family. Leaves have multiple layered
      palisade parenchyma and parenchyma bundle sheaths and could not be categorized as
      xeromorphic because they possess mesomorphic leaf features as simple lamina,
      single-layered epidermis, and soft large-size glabrous leaves with high specific
      leaf area. CONCLUSIONS: The combination of mesomorphic and few xeromorphic foliar
      traits with other characters at the genus and tribal level probably has been
      essential in Asteraceae to colonize various environments, including those with
      low water and nutrient availability.

PMID- 28510196
TI  - Anti-fungal activity, mechanism studies on alpha-Phellandrene and Nonanal against
      Penicillium cyclopium.
AB  - BACKGROUND: Essential oils from plants have been reported to have wide spread
      antimicrobial activity against various bacterial and fungal pathogens, and these
      include alpha-Phellandrene, Nonanal and other volatile substances. However,
      biological activities of alpha-Phellandrene and Nonanal have been reported only
      in a few publications. Further investigations are necessary to determine the
      antimicrobial activity of these compounds, especially for individual application,
      to establish the possible mechanism of action of the most active compound.
      RESULTS: The results are shown that alpha-Phellandrene and Nonanal have a dose
      dependent inhibition on the mycelial growth of Penicillium cyclopium. The minimum
      inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) are 1.7
      and 1.8 mL/L for alpha-Phellandrene, 0.3 and 0.4 mL/L for Nonanal, respectively.
      The volatile compounds altered the morphology of P. cyclopium hyphae by causing
      loss of cytoplasmic material and distortion of the mycelia. The membrane
      permeability of P. cyclopium increased with increasing concentrations of the two
      volatile compounds, as evidenced by cell constituent release, extracellular
      conductivity and induced efflux of K+. Moreover, the two volatile compounds
      induced a decrease in pH and in the total lipid content of P. cyclopium, which
      suggested that cell membrane integrity had been compromised. CONCLUSIONS: The
      results demonstrated that alpha-Phellandrene and Nonanal could significantly
      inhibit the mycelia growth of P. cyclopium by severely disrupting the integrity
      of the fungal cell membrane, leading to the leakage of cell constituents and
      potassium ions, and triggering an increase of the total lipid content,
      extracellular pH and membrane permeability. Our present study suggests that alpha
      Phellandrene and Nonanal might be a biological fungicide for the control of P.
      cyclopium in postharvest tomato fruits.

PMID- 28510197
TI  - Assimilates mobilization, stable canopy temperature and expression of expansin
      stabilizes grain weight in wheat cultivar LOK-1 under different soil moisture
      conditions.
AB  - BACKGROUND: Grain yield of wheat is primarily determined by both grain number and
      grain weight, which often influence each other in response to environmental
      stimuli. Some of the genotypes are capable of maintaining high single grain
      weight (SGW) across the environments. Understanding mechanisms and factors
      associated with the superiority of such genotypes over others is necessary to
      enhance productivity of wheat. RESULTS: Experiments were conducted to elucidate
      the physiological basis of high SGW of LOK-1, a wheat cultivar grown in dry and
      hot environments in the central and peninsular zones of India. SGW of LOK-1 was
      least affected by removal of spikelets indicating little competition between the
      grains within the spike for assimilates. Reduction in SGW due to defoliation was
      less and the contribution of stem reserves to the grain development was high in
      LOK-1 relative to other cultivars. It seems that high level of expression of
      genes such as expansin (TaExpA6) contributes to the high SGW of LOK-1.
      CONCLUSIONS: Source was not a limiting factor for grain growth of LOK-1 in
      contrast to other cultivars, whereas sink appeared to be a limiting factor in
      recently released/identified cultivars. Differences in the amounts of water
      soluble stem carbohydrate reserves translocated to grain could be one of the
      factors contributing to higher grain weight in LOK-1. High level expression of
      TaExpA6, one of the genes contributing to the elongation of endosperm, seems to
      be crucial for grain growth in wheat.

PMID- 28510198
TI  - Investigation of floristic similarities between Taiwan and terrestrial ecoregions
      in Asia using GBIF data.
AB  - BACKGROUND: Floristic compositions of non-endemic plants of continental islands
      were related to the neighboring continents because non-endemic plant species had
      historically migrated to continental islands from source areas. This study
      attempts to identify source areas of a continental island by means of floristic
      analysis and to assess possible migration routes on the basis of geographical
      distribution ranges of plants. Large quantities of angiosperm data records were
      downloaded from the Global Biodiversity Information Facility (GBIF). Similarity
      index and cluster analysis were used to identify the floristic similarities among
      22 geographical localities of Taiwan (GLTs) and 34 terrestrial ecoregions in
      Asia. Geographical distribution ranges of non-endemic angiosperm species in
      Taiwan (NEASTs) were evaluated to mirror the possible migration routes from
      different source areas to Taiwan. RESULTS: There are 3275 angiosperm species in
      Taiwan derived from the dataset of GBIF. Among them, 847 are endemic and 2428 are
      NEASTs. Geographical distribution ranges of the 2428 NEASTs were categorized into
      7 distribution groups. They were widely distribution from equator to Siberia (27
      species), tropical ecoregions (345 species), tropical and subtropical ecoregions
      (663 species), tropical to temperate ecoregions (591 species), subtropical
      ecoregions (265 species), subtropical to temperate ecoregions (387 species), and
      temperate ecoregions (150 species). Results of similarity indices and cluster
      analysis demonstrated that high floristic similarities were observed among GLTs
      at lowland and southern Taiwan and tropical and subtropical ecoregions in Asia.
      GLTs at high mountains were assumed to have floristic similarity with temperate
      ecoregions in Asia, whereas the assumption was not supported by our analysis. It
      is partly because of that angiosperms with tropical and subtropical distributions
      extend their ranges from low to high elevations in Taiwan. CONCLUSIONS:
      Subtropical ecoregions at southern China and tropical ecoregions at Indochina
      were more important than temperate ecoregions on playing source areas of NEASTs.
      Geographical distribution ranges of NEASTs implied that most of the NEASTs were
      probably migrated from topical or subtropical ecoregions of Asian continent to
      Taiwan.

PMID- 28510199
TI  - Taxonomic placement of Paphiopedilum rungsuriyanum (Cypripedioideae; Orchidaceae)
      based on morphological, cytological and molecular analyses.
AB  - BACKGROUND: Paphiopedilum rungsuriyanum from Northern Laos was discovered and
      described in 2014. It is characterized by having miniature tessellated leaves, a
      flower having a helmet shaped lip with a V-shaped neckline, and a semi-lunate, 3
      dentate staminode with an umbo. These morphological features distinguish P.
      rungsuriyanum from the other known sections/subgenera of Paphiopedilum, making it
      difficult to group with existing infrageneric units. RESULTS: Paphiopedilum
      rungsuriyanum has chromosome number of 2n = 26. Fluorescence in situ
      hybridization study demonstrates that there are two 45S rDNA signals in the
      telomeric region of chromosomes, and more than 20 5S rDNA signals dispersed
      signals in the pericentromeric and centromeric regions. Phylogenetic analyses
      based on four nuclear (i.e. ITS, ACO, DEF4 and RAD51) and four plastid (i.e. atpI
      atpH, matK, trnS-trnfM and ycf1) gene regions indicate that P. rungsuriyanum is
      nested in subgenus Paphiopedilum and is a sister to section Paphiopedilum.
      CONCLUSIONS: The results in combination with karyomorphological, rDNA FISH
      patterns, morphological and phylogenetic analyses suggest a new section Laosianum
      to accommodate this species in the current sectional circumscription of subgenus
      Paphiopedilum.

PMID- 28510200
TI  - Cambial variations of Piper (Piperaceae) in Taiwan.
AB  - BACKGROUND: Cambial variations in lianas of Piperaceae in Taiwan have not been
      studied previously. The stem anatomy of seven Piper species from Taiwan was
      examined to document cambial variations and better distinguish the species when
      leaves are absent. RESULTS: A key for the seven species is provided, based on the
      internal stem anatomy. The seven Piper species climb via adventitious roots, and
      in cross section, the stems were generally eccentric and oblate, although a
      transversely elliptic stem was found in P. kadsura (Choisy) Ohwi and P.
      sintenense Hatus. A cambial variant with secondary growth of external primary
      vascular bundles and xylem in plates was observed in all species except Piper
      betle L., which developed another cambium variant with xylem furrowed deeply by
      parenchyma proliferation. The sclerenchymatous ring surrounding the medullary
      vascular bundles was always continuous except in P. betle, where it was
      discontinuous. Mucilage canals varied from absent to present in the center of the
      pith, or present in the pith and inner cortex. Different sizes of vessels
      dispersed throughout the stem were ring or diffuse porous. The numbers of
      medullary and peripheral vascular bundles were distinctive and the widths of rays
      were noticeably different in each species. Differences in the growth rate of the
      medullary vascular bundles produced two development types of vascular bundles,
      although in both types, the peripheral vascular bundles gradually lengthen and
      become separated from each other by wide rays. CONCLUSIONS: We documented the
      internal stem anatomy of six previously unstudied species of Piper, including
      three endemic species, P. kwashoense Hayata, P. sintenense, and P. taiwanense Lin
      and Lu, and found that P. betle had deeply furrowed xylem, which had not been
      reported for the species before. The descriptions and photographs of seven Piper
      species will also provide a basis for further morphological studies.

PMID- 28510201
TI  - Ultramafic geoecology of South and Southeast Asia.
AB  - Globally, ultramafic outcrops are renowned for hosting floras with high levels of
      endemism, including plants with specialised adaptations such as nickel or
      manganese hyperaccumulation. Soils derived from ultramafic regoliths are
      generally nutrient-deficient, have major cation imbalances, and have concomitant
      high concentrations of potentially phytotoxic trace elements, especially nickel.
      The South and Southeast Asian region has the largest surface occurrences of
      ultramafic regoliths in the world, but the geoecology of these outcrops is still
      poorly studied despite severe conservation threats. Due to the paucity of
      systematic plant collections in many areas and the lack of georeferenced
      herbarium records and databased information, it is not possible to determine the
      distribution of species, levels of endemism, and the species most threatened.
      However, site-specific studies provide insights to the ultramafic geoecology of
      several locations in South and Southeast Asia. The geoecology of tropical
      ultramafic regions differs substantially from those in temperate regions in that
      the vegetation at lower elevations is generally tall forest with relatively low
      levels of endemism. On ultramafic mountaintops, where the combined forces of
      edaphic and climatic factors intersect, obligate ultramafic species and
      hyperendemics often occur. Forest clearing, agricultural development, mining, and
      climate change-related stressors have contributed to rapid and unprecedented loss
      of ultramafic-associated habitats in the region. The geoecology of the large
      ultramafic outcrops of Indonesia's Sulawesi, Obi and Halmahera, and many other
      smaller outcrops in South and Southeast Asia, remains largely unexplored, and
      should be prioritised for study and conservation.

PMID- 28510202
TI  - Small agarics in Taiwan: Mycena albopilosa sp. nov. and Gloiocephala epiphylla.
AB  - BACKGROUND: Small agarics are poorly documented in Taiwan, with previously
      reported species either rudimentarily described or lacking a description or
      diagnosis in most cases. A survey on small agarics in a lowland forest of Taiwan
      revealed two species previously unrecorded. RESULTS: One agaric, which is
      characterized mainly by white hairs overlying the pileus, a conspicuous cup
      shaped basal disc surrounding the stipe, and inamyloid basidiospores, fits the
      genus Mycena and appears undescribed. It readily produced abundant basidiomata in
      culture in three weeks. The other agaric is Gloiocephala epiphylla, being
      characterized by its reduced hymenium and conspicuous pileogloeocystidia. ITS
      sequences from the two agarics further corroborated the identifications. Their
      macroscopic and microscopic features and culture morphology are described. A
      dichotomous key is provided to the species of Mycena reported in Taiwan.
      CONCLUSION: The Mycena species is newly described as M. albopilosa herein.
      Gloiocephala epiphylla is new to Taiwan, being the only species of the genus
      known on the island.

PMID- 28510203
TI  - Begonia myanmarica (Begoniaceae), a new species from Myanmar, and molecular
      phylogenetics of Begonia sect. Monopteron.
AB  - BACKGROUND: A new species, Begonia myanmarica, was discovered from Myanmar and
      herein documented. Characterized by a single developed wing in the ovary/fruit,
      this species would be assigned to sect. Monopteron (sensu Doorenbos et al. in The
      sections of Begonia including descriptions, keys and species lists: studies in
      Begoniaceae VI. Wageningen Agricultural University, Wageningen, 1998) that is
      known by B. griffithiana and B. nepalensis from the Himalaya. To confirm its
      sectional assignment, we conducted morphological, phylogenetic and cytological
      studies. RESULTS: Morphological observations indicated that B. myanmarica was
      distinguishable from the two known species of sect. Monopteron by the leaf shape
      and size, 1-locular ovary, parietal placentation and chromosome number. Molecular
      phylogenetic analysis using nrITS sequences showed that B. myanmarica was not
      allied with the clade of sect. Monopteron, though both were nested within sect.
      Platycentrum-sect. Sphenanthera clade. CONCLUSIONS: Studies of morphology,
      molecular phylogenetics and cytology support the recognition of the new species,
      Begonia myanmarica, which is fully described and illustrated. Our results also
      indicate that B. myanmarica is not closely related to species previously assigned
      to sect. Monopteron, suggesting that the fruit morphology of a single developed
      wing in the ovary/fruit characterizing sect. Monopteron is homoplasious.

PMID- 28510204
TI  - Microarray meta-analysis to explore abiotic stress-specific gene expression
      patterns in Arabidopsis.
AB  - BACKGROUND: Abiotic stresses are the major limiting factors that affect plant
      growth, development, yield and final quality. Deciphering the underlying
      mechanisms of plants' adaptations to stresses using few datasets might overlook
      the different aspects of stress tolerance in plants, which might be
      simultaneously and consequently operated in the system. Fortunately, the
      accumulated microarray expression data offer an opportunity to infer abiotic
      stress-specific gene expression patterns through meta-analysis. In this study, we
      propose to combine microarray gene expression data under control, cold, drought,
      heat, and salt conditions and determined modules (gene sets) of genes highly
      associated with each other according to the observed expression data. RESULTS: By
      analyzing the expression variations of the Eigen genes from different conditions,
      we had identified two, three, and five gene modules as cold-, heat-, and salt
      specific modules, respectively. Most of the cold- or heat-specific modules were
      differentially expressed to a particular degree in shoot samples, while most of
      the salt-specific modules were differentially expressed to a particular degree in
      root samples. A gene ontology (GO) analysis on the stress-specific modules
      suggested that the gene modules exclusively enriched stress-related GO terms and
      that different genes under the same GO terms may be alternatively disturbed in
      different conditions. The gene regulatory events for two genes, DREB1A and DEAR1,
      in the cold-specific gene module had also been validated, as evidenced through
      the literature search. CONCLUSIONS: Our protocols study the specificity of the
      gene modules that were specifically activated under a particular type of abiotic
      stress. The biplot can also assist to visualize the stress-specific gene modules.
      In conclusion, our approach has the potential to further elucidate mechanisms in
      plants and beneficial for future experiments design under different abiotic
      stresses.

PMID- 28510205
TI  - The lipid network.
AB  - Natural cell membranes are composed of a remarkable variety of lipids, which
      provide specific biophysical properties to support membrane protein function. An
      improved understanding of this complexity of membrane composition may also allow
      the design of membrane active drugs. Crafting a relevant model of a cell membrane
      with controlled composition is becoming an art, with the ability to reveal the
      molecular mechanisms of biological processes and lead to better treatment of
      pathologies. By matching physiological observations from in vivo experiments to
      high-resolution information, more easily obtained from in vitro studies, complex
      interactions at the lipid interface are determined. The role of the lipid network
      in biological membranes is, therefore, the subject of increasing attention.

PMID- 28510206
TI  - Contributions of fluorescence techniques to understanding G protein-coupled
      receptor dimerisation.
AB  - G protein-coupled receptors (GPCRs) are the largest class of eukaryotic cell
      surface receptors and, over the last decade, it has become clear that they are
      capable of dimerisation. Whilst many biochemical and biophysical approaches have
      been used to study dimerisation, fluorescence techniques, including Forster
      resonance energy transfer and single molecule fluorescence, have been key
      players. Here we review recent contributions of fluorescence techniques to
      investigate GPCR dimers, including dimerisation in cell membranes and native
      tissues, the effect of ligand binding on dimerisation and the kinetics of dimer
      formation and dissociation. The challenges of studying multicomponent membrane
      protein systems have led to the development and refinement of many fluorescence
      assays, allowing the functional consequences of receptor dimerisation to be
      investigated and individual protein molecules to be imaged in the membranes of
      living cells. It is likely that the fluorescence techniques described here will
      be of use for investigating many other multicomponent membrane protein systems.

PMID- 28510207
TI  - Gold nanoclusters as novel optical probes for in vitro and in vivo fluorescence
      imaging.
AB  - Fluorescent probes play an important role in the development of fluorescence
      based imaging techniques for life sciences research. Gold nanoclusters (AuNCs)
      are a novel type of fluorescent nanomaterials which have attracted great interest
      in recent years. Composed of only a few atoms, these ultrasmall AuNCs exhibit
      quantum confinement effects and molecule-like properties. Fluorescent AuNCs have
      an attractive set of features including ultrasmall size, good biocompatibility
      and photostability, and tunable emission in the red to near-infrared spectral
      region, which make them promising as fluorescent labels for biological imaging.
      Examples of their application include live cell labeling, cancer cell targeting,
      cellular apoptosis monitoring, and in vivo tumor imaging. Here, we present a
      brief overview of recent advances in utilizing these emissive ultrasmall AuNCs as
      optical probes for in vitro and in vivo fluorescence imaging.

PMID- 28510208
TI  - Mesoscopic analysis of motion and conformation of cross-bridges.
AB  - The orientation of a cross-bridge is widely used as a parameter in determining
      the state of muscle. The conventional measurements of orientation, such as that
      made by wide-field fluorescence microscopy, electron paramagnetic resonance (EPR)
      or X-ray diffraction or scattering, report the average orientation of 1012-109
      myosin cross-bridges. Under conditions where all the cross-bridges are immobile
      and assume the same orientation, for example in normal skeletal muscle in rigor,
      it is possible to determine the average orientation from such global
      measurements. But in actively contracting muscle, where a parameter indicating
      orientation fluctuates in time, the measurements of the average value provide no
      information about cross-bridge kinetics. To avoid problems associated with
      averaging information from trillions of cross-bridges, it is necessary to
      decrease the number of observed cross-bridges to a mesoscopic value (i.e. the
      value affected by fluctuations around the average). In such mesoscopic regimes,
      the averaging of the signal is minimal and dynamic behavior can be examined in
      great detail. Examples of mesoscopic analysis on skeletal and cardiac muscle are
      provided.

PMID- 28510209
TI  - Nonlinear optical microscopy in decoding arterial diseases.
AB  - Pathological understanding of arterial diseases is mainly attributable to
      histological observations based on conventional tissue staining protocols. The
      emerging development of nonlinear optical microscopy (NLOM), particularly in
      second-harmonic generation, two-photon excited fluorescence and coherent Raman
      scattering, provides a new venue to visualize pathological changes in the
      extracellular matrix caused by atherosclerosis progression. These techniques in
      general require minimal tissue preparation and offer rapid three-dimensional
      imaging. The capability of label-free microscopic imaging enables disease impact
      to be studied directly on the bulk artery tissue, thus minimally perturbing the
      sample. In this review, we look at recent progress in applications related to
      arterial disease imaging using various forms of NLOM.

PMID- 28510210
TI  - Brain connectivity during encoding and retrieval of spatial information:
      individual differences in navigation skills.
AB  - Emerging evidence suggests that the variations in the ability to navigate through
      any real or virtual environment are accompanied by distinct underlying cortical
      activations in multiple regions of the brain. These activations may appear due to
      the use of different frame of reference (FOR) for representing an environment.
      The present study investigated the brain dynamics in the good and bad navigators
      using Graph Theoretical analysis applied to low-density electroencephalography
      (EEG) data. Individual navigation skills were rated according to the performance
      in a virtual reality (VR)-based navigation task and the effect of navigator's
      proclivity towards a particular FOR on the navigation performance was explored.
      Participants were introduced to a novel virtual environment that they learned
      from a first-person or an aerial perspective and were subsequently assessed on
      the basis of efficiency with which they learnt and recalled. The graph
      theoretical parameters, path length (PL), global efficiency (GE), and clustering
      coefficient (CC) were computed for the functional connectivity network in the
      theta and alpha frequency bands. During acquisition of the spatial information,
      good navigators were distinguished by a lower degree of dispersion in the
      functional connectivity compared to the bad navigators. Within the groups of good
      and bad navigators, better performers were characterised by the formation of
      multiple hubs at various sites and the percentage of connectivity or small world
      index. The proclivity towards a specific FOR during exploration of a new
      environment was not found to have any bearing on the spatial learning. These
      findings may have wider implications for how the functional connectivity in the
      good and bad navigators differs during spatial information acquisition and
      retrieval in the domains of rescue operations and defence systems.

PMID- 28510211
TI  - Insights into genome architecture deduced from the properties of short Lac
      repressor-mediated DNA loops.
AB  - Genomic DNA is vastly longer than the space allotted to it in a cell. The
      molecule must fold with a level of organization that satisfies the imposed
      spatial constraints as well as allow for the processing of genetic information.
      Key players in this organization include the negative supercoiling of DNA, which
      facilitates the unwinding of the double-helical molecule, and the associations of
      DNA with proteins, which partition the DNA into isolated loops, or domains. In
      order to gain insight into the principles of genome organization and to visualize
      the folding of spatially constrained DNA, we have developed new computational
      methods to identify the preferred three-dimensional pathways of protein-mediated
      DNA loops and to characterize the topological properties of these structures.
      Here, we focus on the levels of supercoiling and the spatial arrangements of DNA
      in model nucleoprotein systems with two topological domains. We construct these
      systems by anchoring DNA loops in opposing orientations on a common protein-DNA
      assembly, namely the Lac repressor protein with two bound DNA operators. The
      linked pieces of DNA form a covalently closed circle such that the protein
      attaches to two widely spaced sites along the DNA. We examine the effects of
      operator spacing, loop orientation, and long-range contacts on overall chain
      configuration and topology, and discuss our findings in the context of classic
      experiments on the effects of supercoiling and operator spacing on Lac repressor
      mediated looping and recent work on the role of proteins as barriers that divide
      genomes into independent topological domains.

PMID- 28510213
TI  - The emerging role of DNA supercoiling as a dynamic player in genomic structure
      and function.
AB  - This editorial highlights the pervasive role of DNA supercoiling in genomic
      structure and function and introduces the main themes of the reviews in this
      Special Issue.

PMID- 28510214
TI  - Biophysical Reviews publications on DNA structure and function that complement
      this Special Issue on DNA supercoiling.

PMID- 28510212
TI  - Supercoiling biases the formation of loops involved in gene regulation.
AB  - The function of DNA as a repository of genetic information is well-known. The
      post-genomic effort is to understand how this information-containing filament is
      chaperoned to manage its compaction and topological states. Indeed, the
      activities of enzymes that transcribe, replicate, or repair DNA are regulated to
      a large degree by access. Proteins that act at a distance along the filament by
      binding at one site and contacting another site, perhaps as part of a bigger
      complex, create loops that constitute topological domains and influence
      regulation. DNA loops and plectonemes are not necessarily spontaneous, especially
      large loops under tension for which high energy is required to bring their ends
      together, or small loops that require accessory proteins to facilitate DNA
      bending. However, the torsion in stiff filaments such as DNA dramatically
      modulates the topology, driving it from extended and genetically accessible to
      more looped and compact, genetically secured forms. Furthermore, there are
      accessory factors that bias the response of the DNA filament to supercoiling. For
      example, small molecules like polyamines, which neutralize the negative charge
      repulsions along the phosphate backbone, enhance flexibility and promote writhe
      over twist in response to torsion. Such increased flexibility likely pushes the
      topological equilibrium from twist toward writhe at tensions thought to exist in
      vivo. A predictable corollary is that stiffening DNA antagonizes looping and
      bending. Certain sequences are known to be more or less flexible or to exhibit
      curvature, and this may affect interactions with binding proteins. In vivo all of
      these factors operate simultaneously on DNA that is generally negatively
      supercoiled to some degree. Therefore, in order to better understand gene
      regulation that involves protein-mediated DNA loops, it is critical to understand
      the thermodynamics and kinetics of looping in DNA that is under tension,
      negatively supercoiled, and perhaps exposed to molecules that alter elasticity.
      Recent experiments quantitatively reveal how much negatively supercoiling DNA
      lowers the free energy of looping, possibly biasing the operation of genetic
      switches.

PMID- 28510215
TI  - Species-specific supercoil dynamics of the bacterial nucleoid.
AB  - Bacteria organize DNA into self-adherent conglomerates called nucleoids that are
      replicated, transcribed, and partitioned within the cytoplasm during growth and
      cell division. Three classes of proteins help condense nucleoids: (1) DNA gyrase
      generates diffusible negative supercoils that help compact DNA into a dynamic
      interwound and multiply branched structure; (2) RNA polymerase and abundant small
      basic nucleoid-associated proteins (NAPs) create constrained supercoils by
      binding, bending, and forming cooperative protein-DNA complexes; (3) a multi
      protein DNA condensin organizes chromosome structure to assist sister chromosome
      segregation after replication. Most bacteria have four topoisomerases that
      participate in DNA dynamics during replication and transcription. Gyrase and
      topoisomerase I (Topo I) are intimately involved in transcription; Topo III and
      Topo IV play critical roles in decatenating and unknotting DNA during and
      immediately after replication. RNA polymerase generates positive (+) supercoils
      downstream and negative (-) supercoils upstream of highly transcribed operons.
      Supercoil levels vary under fast versus slow growth conditions, but what
      surprises many investigators is that it also varies significantly between
      different bacterial species. The MukFEB condensin is dispensable in the high
      supercoil density (sigma) organism Escherichia coli but is essential in
      Salmonella spp. which has 15 % fewer supercoils. These observations raise two
      questions: (1) How do different species regulate supercoil density? (2) Why do
      closely related species evolve different optimal supercoil levels? Control of
      supercoil density in E. coli and Salmonella is largely determined by differences
      encoded within the gyrase subunits. Supercoil differences may arise to minimalize
      toxicity of mobile DNA elements in the genome.

PMID- 28510218
TI  - Controlling gene expression by DNA mechanics: emerging insights and challenges.
AB  - Transcription initiation is a major control point for the precise regulation of
      gene expression. Our knowledge of this process has been mainly derived from
      protein-centric studies wherein cis-regulatory DNA sequences play a passive role,
      mainly in arranging the protein machinery to coalesce at the transcription start
      sites of genes in a spatial and temporal-specific manner. However, this is a
      highly dynamic process in which molecular motors such as RNA polymerase II
      (RNAPII), helicases, and other transcription factors, alter the level of
      mechanical force in DNA, rather than simply a set of static DNA-protein
      interactions. The double helix is a fiber that responds to flexural and torsional
      stress, which if accumulated, can affect promoter output as well as change DNA
      and chromatin structure. The relationship between DNA mechanics and the control
      of early transcription initiation events has been under-investigated. Genomic
      techniques to display topological stress and conformational variation in DNA
      across the mammalian genome provide an exciting new insight on the role of DNA
      mechanics in the early stages of the transcription cycle. Without understanding
      how torsional and flexural stresses are generated, transmitted, and dissipated,
      no model of transcription will be complete and accurate.

PMID- 28510217
TI  - Protein-induced DNA linking number change by sequence-specific DNA binding
      proteins and its biological effects.
AB  - Sequence-specific DNA-binding proteins play essential roles in many fundamental
      biological events such as DNA replication, recombination, and transcription. One
      common feature of sequence-specific DNA-binding proteins is to introduce
      structural changes to their DNA recognition sites including DNA-bending and DNA
      linking number change (DeltaLk). In this article, I review recent progress in
      studying protein-induced DeltaLk by several sequence-specific DNA-binding
      proteins, such as E. coli cAMP receptor protein (CRP) and lactose repressor
      (LacI). It was demonstrated recently that protein-induced DeltaLk is an intrinsic
      property for sequence-specific DNA-binding proteins and does not correlate to
      protein-induced other structural changes, such as DNA bending. For instance,
      although CRP bends its DNA recognition site by 90 degrees , it was not able to
      introduce a DeltaLk to it. However, LacI was able to simultaneously bend and
      introduce a DeltaLk to its DNA binding sites. Intriguingly, LacI also constrained
      superhelicity within LacI-lac O1 complexes if (-) supercoiled DNA templates were
      provided. I also discuss how protein-induced DeltaLk help sequence-specific DNA
      binding proteins regulate their biological functions. For example, it was shown
      recently that LacI utilizes the constrained superhelicity (DeltaLk) in LacI-lac
      O1 complexes and serves as a topological barrier to constrain free, unconstrained
      (-) supercoils within the 401-bp DNA loop. These constrained (-) supercoils
      enhance LacI's binding affinity and therefore the repression of the lac promoter.
      Other biological functions include how DNA replication initiators lambda O and
      DnaA use the induced DeltaLk to open/melt bacterial DNA replication origins.

PMID- 28510219
TI  - The dynamic interplay between DNA topoisomerases and DNA topology.
AB  - Topological properties of DNA influence its structure and biochemical
      interactions. Within the cell, DNA topology is constantly in flux. Transcription
      and other essential processes, including DNA replication and repair, not only
      alter the topology of the genome but also introduce additional complications
      associated with DNA knotting and catenation. These topological perturbations are
      counteracted by the action of topoisomerases, a specialized class of highly
      conserved and essential enzymes that actively regulate the topological state of
      the genome. This dynamic interplay among DNA topology, DNA processing enzymes,
      and DNA topoisomerases is a pervasive factor that influences DNA metabolism in
      vivo. Building on the extensive structural and biochemical characterization over
      the past four decades that has established the fundamental mechanistic basis of
      topoisomerase activity, scientists have begun to explore the unique roles played
      by DNA topology in modulating and influencing the activity of topoisomerases. In
      this review we survey established and emerging DNA topology-dependent protein-DNA
      interactions with a focus on in vitro measurements of the dynamic interplay
      between DNA topology and topoisomerase activity.

PMID- 28510216
TI  - DNA supercoiling is a fundamental regulatory principle in the control of
      bacterial gene expression.
AB  - Although it has become routine to consider DNA in terms of its role as a carrier
      of genetic information, it is also an important contributor to the control of
      gene expression. This regulatory principle arises from its structural properties.
      DNA is maintained in an underwound state in most bacterial cells and this has
      important implications both for DNA storage in the nucleoid and for the
      expression of genetic information. Underwinding of the DNA through reduction in
      its linking number potentially imparts energy to the duplex that is available to
      drive DNA transactions, such as transcription, replication and recombination. The
      topological state of DNA also influences its affinity for some DNA binding
      proteins, especially in DNA sequences that have a high A + T base content. The
      underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a
      continuum between metabolic flux, DNA topology and gene expression that underpins
      the global response of the genome to changes in the intracellular and external
      environments. These connections describe a fundamental and generalised mechanism
      affecting global gene expression that underlies the specific control of
      transcription operating through conventional transcription factors. This
      mechanism also provides a basal level of control for genes acquired by horizontal
      DNA transfer, assisting microbial evolution, including the evolution of
      pathogenic bacteria.

PMID- 28510221
TI  - Development of a dual-expression vector facilitated with selection-free PCR
      recombination cloning strategy.
AB  - The conventional procedure for the construction of recombinant expression vector
      of a target gene includes PCR cloning and restriction enzyme mediated subcloning,
      which is time-consuming and sometimes troublesome because of the inefficiency of
      ligation. A variety of ligase-independent PCR cloning strategies have been
      developed, but they either involve complicated PCR procedures or need other DNA
      modifying enzymes. In this study, we report the design, and construction of an
      omnipotent expression vector pOmni, with which a target gene can be easily cloned
      through innovative selection-free PCR recombination cloning strategy with only
      one pair of primer and two times of PCR in one work day, without using any
      restriction enzymes, ligase and other DNA modifying enzymes. Furthermore, the
      target gene cloned in pOmni is ready to be high-efficiently expressed in either
      Escherichia coli cells or eukaryotic cells because of the elaborate design of
      compatible T7 promoter and CMV promoter expression elements in the vector. The
      cloning capability and reliability of selection-free PCR recombination cloning
      with pOmni were validated through cloning of 6 DNA fragments with length from 315
      to 4557 bp, and the dual-expression function of the vector was verified through
      the cloning and expression of EGFP in E. coli BL21 and HeLa cells. pOmni
      developed in our study provides a powerful tool for gene cloning and expression,
      and is of special value for researches in which both prokaryotic and eukaryotic
      expression of a target gene are necessary.

PMID- 28510222
TI  - Primary ectopic breast cancer of the vulva, treated with local excision of the
      vulva and sentinel lymph node biopsy: a case report.
AB  - Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and
      primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases
      have been published in the English-language literature, and there has been no
      report of primary breast carcinoma of the vulva in Japan. We report a rare case
      of primary ectopic breast cancer of the vulva that was treated with local
      excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72
      year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor
      was excised by the Department of Plastic Surgery of our hospital. The histology
      of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and
      immunohistochemical staining of the vulvar specimen showed the tumor cells to be
      100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All
      margins of resection were positive for neoplastic involvement. An additional
      local excision of the vulva and right inguinal SLNB were performed in our
      department. The intraoperative frozen section was negative for metastasis, and
      lymph node dissection was not performed. The final pathology was negative for
      residual disease, and a partially normal ductal component was present. Adjuvant
      hormonal therapy with an aromatase inhibitor was indicated post-operatively. The
      patient was asymptomatic and free of detectable disease at a 6-month follow-up.
      Due to the rarity of this diagnosis, there are no established guidelines for
      treatment. Although cases in which SLNB was performed are rare, we consider SLNB
      to be an effective alternative to inguinal node dissection for ectopic primary
      breast cancer of the vulva.

PMID- 28510220
TI  - The regulatory role of DNA supercoiling in nucleoprotein complex assembly and
      genetic activity.
AB  - We argue that dynamic changes in DNA supercoiling in vivo determine both how DNA
      is packaged and how it is accessed for transcription and for other manipulations
      such as recombination. In both bacteria and eukaryotes, the principal generators
      of DNA superhelicity are DNA translocases, supplemented in bacteria by DNA
      gyrase. By generating gradients of superhelicity upstream and downstream of their
      site of activity, translocases enable the differential binding of proteins which
      preferentially interact with respectively more untwisted or more writhed DNA.
      Such preferences enable, in principle, the sequential binding of different
      classes of protein and so constitute an essential driver of chromatin
      organization.

PMID- 28510223
TI  - Protein-induced DNA linking number change by sequence-specific DNA binding
      proteins and its biological effects.
AB  - Sequence-specific DNA-binding proteins play essential roles in many fundamental
      biological events such as DNA replication, recombination, and transcription. One
      common feature of sequence-specific DNA-binding proteins is to introduce
      structural changes to their DNA recognition sites including DNA-bending and DNA
      linking number change (DeltaLk). In this article, I review recent progress in
      studying protein-induced DeltaLk by several sequence-specific DNA-binding
      proteins, such as E. coli cAMP receptor protein (CRP) and lactose repressor
      (LacI). It was demonstrated recently that protein-induced DeltaLk is an intrinsic
      property for sequence-specific DNA-binding proteins and does not correlate to
      protein-induced other structural changes, such as DNA bending. For instance,
      although CRP bends its DNA recognition site by 90 degrees , it was not able to
      introduce a DeltaLk to it. However, LacI was able to simultaneously bend and
      introduce a DeltaLk to its DNA binding sites. Intriguingly, LacI also constrained
      superhelicity within LacI-lac O1 complexes if (-) supercoiled DNA templates were
      provided. I also discuss how protein-induced DeltaLk help sequence-specific DNA
      binding proteins regulate their biological functions. For example, it was shown
      recently that LacI utilizes the constrained superhelicity (DeltaLk) in LacI-lac
      O1 complexes and serves as a topological barrier to constrain free, unconstrained
      (-) supercoils within the 401-bp DNA loop. These constrained (-) supercoils
      enhance LacI's binding affinity and therefore the repression of the lac promoter.
      Other biological functions include how DNA replication initiators lambda O and
      DnaA use the induced DeltaLk to open/melt bacterial DNA replication origins.

PMID- 28510225
TI  - Controlling gene expression by DNA mechanics: emerging insights and challenges.
AB  - Transcription initiation is a major control point for the precise regulation of
      gene expression. Our knowledge of this process has been mainly derived from
      protein-centric studies wherein cis-regulatory DNA sequences play a passive role,
      mainly in arranging the protein machinery to coalesce at the transcription start
      sites of genes in a spatial and temporal-specific manner. However, this is a
      highly dynamic process in which molecular motors such as RNA polymerase II
      (RNAPII), helicases, and other transcription factors, alter the level of
      mechanical force in DNA, rather than simply a set of static DNA-protein
      interactions. The double helix is a fiber that responds to flexural and torsional
      stress, which if accumulated, can affect promoter output as well as change DNA
      and chromatin structure. The relationship between DNA mechanics and the control
      of early transcription initiation events has been under-investigated. Genomic
      techniques to display topological stress and conformational variation in DNA
      across the mammalian genome provide an exciting new insight on the role of DNA
      mechanics in the early stages of the transcription cycle. Without understanding
      how torsional and flexural stresses are generated, transmitted, and dissipated,
      no model of transcription will be complete and accurate.

PMID- 28510224
TI  - DNA supercoiling is a fundamental regulatory principle in the control of
      bacterial gene expression.
AB  - Although it has become routine to consider DNA in terms of its role as a carrier
      of genetic information, it is also an important contributor to the control of
      gene expression. This regulatory principle arises from its structural properties.
      DNA is maintained in an underwound state in most bacterial cells and this has
      important implications both for DNA storage in the nucleoid and for the
      expression of genetic information. Underwinding of the DNA through reduction in
      its linking number potentially imparts energy to the duplex that is available to
      drive DNA transactions, such as transcription, replication and recombination. The
      topological state of DNA also influences its affinity for some DNA binding
      proteins, especially in DNA sequences that have a high A + T base content. The
      underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a
      continuum between metabolic flux, DNA topology and gene expression that underpins
      the global response of the genome to changes in the intracellular and external
      environments. These connections describe a fundamental and generalised mechanism
      affecting global gene expression that underlies the specific control of
      transcription operating through conventional transcription factors. This
      mechanism also provides a basal level of control for genes acquired by horizontal
      DNA transfer, assisting microbial evolution, including the evolution of
      pathogenic bacteria.

PMID- 28510226
TI  - The ribosome's energy landscape: Recent insights from computation.
AB  - The ever-increasing capacity of computing resources has extended ribosome
      calculations from the study of small-scale fluctuations to large-scale barrier
      crossing processes. As the field of computational/theoretical biophysics shifts
      focus to large-scale conformational transitions, there is a growing need for a
      systematic framework to interpret and analyze ribosome dynamics. To this end,
      energy landscape principles, largely developed for the study of biomolecular
      folding, have proven to be invaluable. These tools not only provide a foundation
      for describing simulations but can be used to reconcile experimental results, as
      well. In this review, I will discuss recent efforts to employ computational
      methods to reveal the characteristics of the ribosome's landscape and how these
      studies can help guide a new generation of experiments that more closely probe
      the underlying energetics. As a result of these investigations, general
      principles about ribosome function are beginning to emerge, including that: (1)
      small-scale fluctuations are the result of structure, rather than detailed
      energetics, (2) molecular flexibility leads to entropically favored
      rearrangements, and (3) tRNA dynamics may be accurately described as diffusive
      movement across an energy landscape.

PMID- 28510228
TI  - Oriented samples: a tool for determining the membrane topology and the mechanism
      of action of cationic antimicrobial peptides by solid-state NMR.
AB  - Overuse and misuse of antibiotics have led bacteria to acquire several mechanisms
      of resistance. In response to this, researchers have identified natural
      antimicrobial peptides as promising candidates to fight against multiresistant
      bacteria. However, their mode of action is still unclear, and a better
      understanding of the mode of action of these peptides is of primary importance to
      develop new peptides displaying high antibacterial activity and low hemolytic
      activity. One of the main features that defines the mechanism of action is the
      membrane topology of the peptide. Among the spectroscopic techniques, solid-state
      NMR is the technique of choice for determining the location of the peptide within
      the membrane. It can be achieved by performing experiments with oriented samples.
      In the literature, the two most common types of oriented samples are bicelles and
      phospholipids mechanically oriented between glass plates. The mode of
      perturbation of the membrane-active peptide can be studied by phosphorus-31 and
      deuterium NMR. On the other hand, several experiments such as nitrogen-15 and
      fluorine solid-state NMR, that require labeled peptides, can give valuable
      information on the membrane topology of the peptide. The combination of the
      latter techniques allows the determination of a precise topology, thus a better
      knowledge of the molecular determinants involved in the membrane interactions of
      antimicrobial peptides.

PMID- 28510230
TI  - How to test bioinformatics software?
AB  - Bioinformatics is the application of computational, mathematical and statistical
      techniques to solve problems in biology and medicine. Bioinformatics programs
      developed for computational simulation and large-scale data analysis are widely
      used in almost all areas of biophysics. The appropriate choice of algorithms and
      correct implementation of these algorithms are critical for obtaining reliable
      computational results. Nonetheless, it is often very difficult to systematically
      test these programs as it is often hard to verify the correctness of the output,
      and to effectively generate failure-revealing test cases. Software testing is an
      important process of verification and validation of scientific software, but very
      few studies have directly dealt with the issues of bioinformatics software
      testing. In this work, we review important concepts and state-of-the-art methods
      in the field of software testing. We also discuss recent reports on adapting and
      implementing software testing methodologies in the bioinformatics field, with
      specific examples drawn from systems biology and genomic medicine.

PMID- 28510231
TI  - Quantum effects in dynamics of water and other liquids of light molecules.
AB  - Nuclear quantum effects in atomic motions are well known at low temperatures
      [Formula: see text] K, but analyses of structural relaxation in liquids and
      description of the glass transition traditionally neglect quantum effects at
      higher temperatures, [Formula: see text] K. Recent studies, however, suggested
      that nuclear quantum effects in systems of light molecules (e.g., water) might
      play an important role in structural dynamics and provide non-negligible
      contributions at such temperatures, and even up to ambient temperature. In this
      article, we discuss experimental evidences of the quantum effects in glass
      transition in liquids of light molecules and possible theoretical descriptions of
      these effects. We show that quantum effects may qualitatively change the
      temperature behavior of the structural relaxation time in supercooled liquids
      leading to deviations of some well-established properties of the glass transition
      when it happens at low temperatures. We also demonstrate that unusual behavior of
      water dynamics at low temperatures, including apparent fragile-to-strong
      crossover, can be ascribed to nuclear quantum effects.

PMID- 28510227
TI  - Kinesin Motor Enzymology: Chemistry, Structure, and Physics of Nanoscale
      Molecular Machines.
AB  - Molecular motors are enzymes that convert chemical potential energy into
      controlled kinetic energy for mechanical work inside cells. Understanding the
      biophysics of these motors is essential for appreciating life as well as
      apprehending diseases that arise from motor malfunction. This review focuses on
      kinesin motor enzymology with special emphasis on the literature that reports the
      chemistry, structure and physics of several different kinesin superfamily
      members.

PMID- 28510234
TI  - Deriving biomedical diagnostics from NMR spectroscopic data.
AB  - Biomedical spectroscopic experiments generate large volumes of data. For
      accurate, robust diagnostic tools the data must be analyzed for only a few
      characteristic observations per subject, and a large number of subjects must be
      studied. We describe here two of the current data analytic approaches applied to
      this problem: SIMCA (principal component analysis, partial least squares), and
      the statistical classification strategy (SCS). We demonstrate the application of
      the SCS by three examples of its use in analyzing 1H NMR spectra: screening for
      colon cancer, characterization of thyroid cancer, and distinguishing cancer from
      cholangitis in the biliary tract.

PMID- 28510229
TI  - A change of heart: oxidative stress in governing muscle function?
AB  - Redox/cysteine modification of proteins that regulate calcium cycling can affect
      contraction in striated muscles. Understanding the nature of these modifications
      would present the possibility of enhancing cardiac function through reversible
      cysteine modification of proteins, with potential therapeutic value in heart
      failure with diastolic dysfunction. Both heart failure and muscular dystrophy are
      characterized by abnormal redox balance and nitrosative stress. Recent evidence
      supports the synergistic role of oxidative stress and inflammation in the
      progression of heart failure with preserved ejection fraction, in concert with
      endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate
      protein kinase G signalling via modification of the giant protein titin. Although
      antioxidant therapeutics in heart failure with diastolic dysfunction have no
      marked beneficial effects on the outcome of patients, it, however, remains
      critical to the understanding of the complex interactions of
      oxidative/nitrosative stress with pro-inflammatory mechanisms, metabolic
      dysfunction, and the redox modification of proteins characteristic of heart
      failure. These may highlight novel approaches to therapeutic strategies for heart
      failure with diastolic dysfunction. In this review, we provide an overview of
      oxidative stress and its effects on pathophysiological pathways. We describe the
      molecular mechanisms driving oxidative modification of proteins and subsequent
      effects on contractile function, and, finally, we discuss potential therapeutic
      opportunities for heart failure with diastolic dysfunction.

PMID- 28510232
TI  - Network modelling of gene regulation.
AB  - Gene regulatory network (GRN) modelling has gained increasing attention in the
      past decade. Many computational modelling techniques have been proposed to
      facilitate the inference and analysis of GRN. However, there is often confusion
      about the aim of GRN modelling, and how a gene network model can be fully
      utilised as a tool for systems biology. The aim of the present article is to
      provide an overview of this rapidly expanding subject. In particular, we review
      some fundamental concepts of systems biology and discuss the role of network
      modelling in understanding complex biological systems. Several commonly used
      network modelling paradigms are surveyed with emphasis on their practical use in
      systems biology research.

PMID- 28510233
TI  - Filamin structure, function and mechanics: are altered filamin-mediated force
      responses associated with human disease?
AB  - The cytoskeleton framework is essential not only for cell structure and stability
      but also for dynamic processes such as cell migration, division and
      differentiation. The F-actin cytoskeleton is mechanically stabilised and
      regulated by various actin-binding proteins, one family of which are the filamins
      that cross-link F-actin into networks that greatly alter the elastic properties
      of the cytoskeleton. Filamins also interact with cell membrane-associated
      extracellular matrix receptors and intracellular signalling proteins providing a
      potential mechanism for cells to sense their external environment by linking
      these signalling systems. The stiffness of the external matrix to which cells are
      attached is an important environmental variable for cellular behaviour. In order
      for a cell to probe matrix stiffness, a mechanosensing mechanism functioning via
      alteration of protein structure and/or binding events in response to external
      tension is required. Current structural, mechanical, biochemical and human
      disease-associated evidence suggests filamins are good candidates for a role in
      mechanosensing.

PMID- 28510236
TI  - ?

PMID- 28510237
TI  - [Time for legislation on the "doctor consultation apps"].

PMID- 28510238
TI  - ?

PMID- 28510235
TI  - Surfactants in Acute Respiratory Distress Syndrome in Infants and Children: Past,
      Present and Future.
AB  - There is a lack of definitive data on the effective management of acute
      respiratory distress syndrome (ARDS) in infants and children. The development and
      validation of the Berlin definition (BD) for ARDS and the Pediatric Acute Lung
      Injury Consensus Conference (PALICC) recommendations in children represented a
      major advance in optimizing research and treatment, mainly due to the
      introduction of a severe ARDS category. Proposed reasons for the lack of
      consistent results with surfactants in children and infants compared with
      neonates include different causes, type of lung damage (direct or indirect),
      timing and mode of administration as well as the type of surfactant used.
      Secretory phospholipase A2 plays an important role in inflammation and possible
      dysfunction of surfactants in ARDS. Bronchoalveolar lavage (BAL) with normal
      saline and surfactant allows the removal of inhaled material, the recruitment of
      non-ventilating areas and the maintenance of the surfactant pool size. BAL with
      diluted surfactant allows rapid absorption of the surfactant at the air/liquid
      interface, which blocks the progression of pathological lung disease and in turn
      disrupts the inflammatory cycle. Importantly, it is now recognized that the type
      of surfactant, the time of administration and the method of administration could
      all play an important role in the management of ARDS, and there is evidence that
      surfactant is effective and well tolerated in children and infants with ARDS.

PMID- 28510239
TI  - ?

PMID- 28510240
TI  - [Warfarin should not be recommended to anyone with atrial fibrillation].

PMID- 28510241
TI  - [Ketosis-prone type 2 diabetes can be expected to increase in Sweden].

PMID- 28510242
TI  - ?
AB  - Endoscopic surveillance after colorectal polypectomy These guidelines for
      endoscopic surveillance after colorectal polypectomy are based on the
      recommendations published by European Society of Gastrointestinal Endoscopy
      (ESGE) in 2013. A precondition for the guidelines is that patients have undergone
      a high-quality colonoscopy, including complete removal and histopathological
      evaluation of all detected neoplastic lesions. Current research has made it
      possible to stratify patients into a low-risk and a high-risk group in terms of
      metachronous cancer. Low-risk group patients (1-2 tubular adenomas <10 mm in
      size) are recommended a surveillance colonoscopy 10 years after the index
      colonoscopy if the patient is less than 50 years old, otherwise not. High-risk
      group patients (adenomas with villous histology or high grade dysplasia or >=10
      mm in size, or >= 3 adenomas), should undergo a repetition colonoscopy 3 years
      after the index colonoscopy. If high-risk adenomas are detected at first or
      subsequent surveillance colonoscopy, a 3-year repetition of the next endoscopic
      examination is recommended. If a high-risk patient has no high-risk adenomas at
      the first surveillance colonoscopy, a 5-year period is recommended until the
      second surveillance colonoscopy. ESGE recommends termination of the follow-up at
      80 years of age although individualised recommendations should consider general
      health and co-morbidity of the patients as well as findings at previous
      colonoscopies.

PMID- 28510243
TI  - ?
AB  - High quality colonoscopy must be secured Colonoscopy plays a key role in the work
      up of digestive diseases and constitutes the cornerstone in colorectal cancer
      diagnosis and prevention. Data suggest that the quality of colonoscopy varies
      widely between different endoscopists. This article summarizes current evidence
      and expert consensus on quality indicators, along with the evidence supporting
      their use in benchmarking, quality reporting, and continuous quality improvement
      in order to secure high quality colonoscopy. In particular, four quality
      indicators, i.e. adenoma detection rate, compliance with guidelines on intervals
      for endoscopic surveillance, cecal intubation rate and complications, should be
      monitored in endoscopy units to ensure that colonoscopy practice is of high
      quality. Proper performance and documentation of high quality colonoscopy is
      critical for reducing colorectal cancer incidence and mortality.

PMID- 28510244
TI  - ?

PMID- 28510245
TI  - Association of three common single nucleotide polymorphisms of SLC7A7 with the
      development of glioma in a Chinese population.
AB  - Gliomas are brain tumors that can be seriously damaging to human health. The SLC7
      family is involved in amino acid or peptide transportation. The relationship
      between SLC7A7 polymorphisms and the development of glioma has been reported
      previously by a few studies. Therefore, we performed a hospital based case
      control study to investigate the association of three common SNPs (rs12888930,
      rs12436190, and rs2065134) of SLC7A7 with the development of glioma in a Chinese
      population. From January 2014 to December 2015, 122 patients with glioma and 252
      individuals (controls) were recruited from the department of neurosurgery of
      Tangshan People's Hospital affiliated to North China University of Science and
      Technology. SLC7A7 rs12888930, rs12436190, and rs2065134 genotyping was performed
      by the polymerase chain reaction-restriction fragment length polymorphism method.
      Multiple logistic regression analysis showed that a significantly higher risk of
      glioma was harbored by the GG and AG + GG genotypes than by the AA genotype; OR
      (95%CI) was 2.24 (1.18-4.22) and 1.59 (1.01-2.60), respectively. However, no
      significant relationship was observed between SLC7A7 rs12888930 and rs2065134 and
      the risk of glioma. In conclusion, this study reports a significant association
      between SLC7A7 rs12436190 and the risk of glioma in a Chinese population.

PMID- 28510246
TI  - Molecular cloning and differential expression of the glucocorticoid receptorgene
      in the estuarine tapertail anchovy Coilia nasus.
AB  - To understand the regulation of the glucocorticoid receptor gene (Gcr) during
      loading and transport stress in fish, the Gcr gene of Coilia nasus was cloned.
      Gcr in C. nasus is expressed strongly in the liver and muscle, and less
      stronglyin the gills, brain, spleen, intestine, trunk kidney, and head kidney.
      Gcr expression in both the liver and muscle was increased by loading and
      transport stress. NaCl reduced the death rate caused by loading and transport
      stress, and the expression of Gcr in liver and muscle differed significantly
      between the NaCl and non-NaCl groups. To investigate whether the elevated Gcr
      transcripts were translated into protein, proteins extracted from the liver and
      muscle were analyzed. In both tissues, C. nasus GCR protein expression patterns
      paralleled those of Gcr mRNA during stress.

PMID- 28510247
TI  - Characterization and development of 56 EST-SSR markers derived from the
      transcriptome of Odontobutis potamophila.
AB  - Expressed sequence tags (ETSs) are the sources of microsatellite development. In
      this study, we isolated and characterized microsatellite markers for Odontobutis
      potamophila by using Illumina RNA-sequencing. We sequenced a large number of ESTs
      and screened 200 potential microsatellites. Consequently, a total of 56 novel
      polymorphic microsatellite repeat markers were identified in thirty-two
      individuals from a wild population area (Jiande, Zhejiang Province, China). The
      number of alleles per locus varied from two to eight, the observed heterozygosity
      (HO) ranged from 0.03571 to 0.9375, and the expected heterozygosity (HE) ranged
      from 0.14326 to 0.81549. The average number of alleles, HO, and HE were 5.0,
      0.4467, and 0.5518, respectively. By the calculation, the range of polymorphism
      information content (PIC) was 0.1177-0.8492. Most of the loci showed moderate or
      high polymorphism. These newly developed EST-simple sequence repeat (EST-SSR)
      markers would serve as an efficient tool for analyzing population connectivity
      and provide sufficient information for genetic diversity research, parentage, and
      molecular breeding of O. potamophila and other fishes with similar genetic
      relationship.

PMID- 28510248
TI  - CADM1 mRNA expression and clinicopathological significance in esophageal squamous
      cell carcinoma tissue.
AB  - The mRNA expression of cell adhesion molecule 1 (CADM1) and its
      clinicopathological significance in esophageal squamous cell carcinoma (ESCC)
      tissues were investigated. CADM1 mRNA and protein expression were detected in
      tissue samples from 50 patients with ESCC by reverse transcription-polymerase
      chain reaction (RT-PCR) and streptavidin-peroxidase (SP) immunohistochemistry;
      adjacent tissues served as controls. The average CADM1 mRNA expression was
      significantly downregulated in the cancer tissues (0.522 +/- 0.247) than in the
      controls (0.871 +/- 0.192), (t = 7.882, P < 0.05). CADM1 mRNA expression was
      significantly downregulated in ESCC patients with positive lymph node metastasis
      than in those with negative lymph node metastasis (t = 3.207, P < 0.05). There
      was a correlation between CADM1 mRNA expression and tumor-node-metastasis (TNM)
      stage (t = 2.673, P < 0.050), but not with age, gender, and histological grade (P
      > 0.05). The positive expression rate of CADM1 protein in the 50 cases of ESCC
      was significantly lower than that of the control group (chi2 = 29.87, P < 0.01).
      Out of 28 patients with non-lymph node metastasis, 20 (71.43%) positively
      expressed CADM1; out of 22 patients with lymph node metastasis, only 7 (31.82%)
      positively expressed CADM1. There was a significant difference in the positive
      protein expression rates of CADM1 between the two groups (chi2 = 7.782, P <
      0.01). CADM1 mRNA expression was highly upregulated in normal tissues compared to
      ESCC tissues, indicating that the loss of CADM1 expression influenced the
      pathogenesis, invasion, and metastasis of ESCC, and allowing for the prognosis of
      the disease in patients with ESCC after treatment.

PMID- 28510249
TI  - Mechanism of pingyangmycin-induced apoptosis of cultured human umbilical vein
      endothelial cells.
AB  - In this study, we investigated the effects of pingyangmycin (PYM) on the growth
      inhibition and apoptosis of human umbilical vein endothelial cells (HUVEC). In
      this study, we aimed to explore the optimal concentration of PYM to induce the
      apoptosis of HUVEC and to determine its mechanism of action. After treatment of
      HUVEC with different concentrations of PYM for 24 h, cell counting kit-8 (CCK-8)
      was used to detect growth inhibiting effects. Annexin V-FITC/propidium iodide
      stain was used to detect apoptosis, and western blot was used to detect the
      expression of glucose-related protein 78 (GPR78) and C/EBP homologous protein
      (CHOP) endoplasmic reticulum stress proteins. With increasing PYM concentration,
      the growth inhibition of HUVEC increased (P < 0.05), the apoptotic numbers of
      HUVEC increased (P < 0.05), with higher PYM concentrations inducing necrosis, and
      the protein expression of GRP78 and CHOP increased (P < 0.05). PYM could
      obviously inhibit the proliferation and promote the apoptosis of HUVEC. Necrotic
      cells were more prevalent than apoptotic cells at high PYM concentrations. This
      study helped to determine the proper concentration of PYM to induce more
      apoptosis than necrosis, which is critical to minimize inflammation, enhance the
      healing of the skin, and maintain safety for the patient. PYM might induce HUVEC
      apoptosis through the endoplasmic reticulum stress pathway.

PMID- 28510250
TI  - A set of novel microsatellite markers developed for an economically important
      tree, Dracontomelon duperreanum, in China.
AB  - Dracontomelon duperreanum, the most representative species of the family
      Anacardiaceae, is an important multipurpose tree in China and Vietnam. However,
      no genetic diversity studies have been reported on this species. In this study,
      we identified 11 microsatellite markers for D. duperreanum by using the
      restriction-site-associated DNA sequencing (RAD-seq) method and examined their
      polymorphisms in 22 samples obtained from the South China Botanical Garden, South
      China. We could detect only two or three alleles for each microsatellite marker.
      The mean observed and expected heterozygosities were 0.41 and 0.39, respectively,
      which were lower than those reported for the species with similar life history
      forms. These relatively low genetic diversities in this common plant species are
      unexpected and might have resulted from its extensive cultivation. To our
      knowledge, this is the first report of microsatellite markers in the genus
      Dracontomelon. These microsatellite markers will be valuable for studying the
      genetic diversities and structures in D. duperreanum and other Dracontomelon
      species.

PMID- 28510252
TI  - Assessing non-additive effects in GBLUP model.
AB  - Understanding non-additive effects in the expression of quantitative traits is
      very important in genotype selection, especially in species where the commercial
      products are clones or hybrids. The use of molecular markers has allowed the
      study of non-additive genetic effects on a genomic level, in addition to a better
      understanding of its importance in quantitative traits. Thus, the purpose of this
      study was to evaluate the behavior of the GBLUP model in different genetic models
      and relationship matrices and their influence on the estimates of genetic
      parameters. We used real data of the circumference at breast height in Eucalyptus
      spp and simulated data from a population of F2. Three commonly reported kinship
      structures in the literature were adopted. The simulation results showed that the
      inclusion of epistatic kinship improved prediction estimates of genomic breeding
      values. However, the non-additive effects were not accurately recovered. The
      Fisher information matrix for real dataset showed high collinearity in estimates
      of additive, dominant, and epistatic variance, causing no gain in the prediction
      of the unobserved data and convergence problems. Estimates presented differences
      of genetic parameters and correlations considering the different kinship
      structures. Our results show that the inclusion of non-additive effects can
      improve the predictive ability or even the prediction of additive effects.
      However, the high distortions observed in the variance estimates when the Hardy
      Weinberg equilibrium assumption is violated due to the presence of selection or
      inbreeding can converge at zero gains in models that consider epistasis in
      genomic kinship.

PMID- 28510251
TI  - Short-term effects of green tea chronotherapy on the metabolic homeostasis of
      mice on different diets.
AB  - Biological rhythms can be defined as changes in physiological or behavioral
      variables that repeat at certain time intervals. Rhythms that last approximately
      24 h are referred to as circadian rhythms. Modern lifestyles have drastically
      affected human habits, as well as the population's eating habits. These changes
      have generated an epidemic of metabolic syndromes, such as obesity and diabetes.
      In an attempt to combat obesity, populations have attempted to use many different
      herbal remedies and plant-based drugs, the most common of which is Camellia
      sinensis, or green tea. Most of the studies on the effects of C. sinensis on
      maintaining body weight have reported the involvement of this substance in lipid
      oxidation. The objective of this study was to evaluate how the administration of
      C. sinensis at different times of day influenced changes in body weight, blood
      glucose levels, and food intake of mice kept under different diet conditions. The
      structural organization of abdominal adipose tissue was also evaluated, as were
      certain aspects of lipid metabolism and overall synthetic activity in the liver,
      adipose tissue, and ovaries. The results obtained suggest that the intake of
      green tea in the light phase of the day stimulates weight loss, regardless of the
      diet ingested. Neither glucose levels nor the structural organization of adipose
      tissue was found to be altered in any of the experimental groups. Neither diet
      nor the time at which the green tea was administered was found to have any
      effects on the amount of food the mice consumed. The time at which green tea was
      consumed and the type of diet both influenced LXRalphabeta nuclear receptor
      expression, as well as the expression of fibrillarin in the liver and ovaries,
      although this influence was tissue specific.

PMID- 28510253
TI  - Feline immunodeficiency virus and feline leukemia virus: frequency and associated
      factors in cats in northeastern Brazil.
AB  - Our aims were to determine the frequencies of feline immunodeficiency virus (FIV)
      and feline leukemia virus (FeLV) in owned and stray cats in the northeastern
      region of Brazil, ascertain the status of FeLV infection, and investigate
      potential associated factors among the owned cats. Blood samples from 200
      asymptomatic owned cats and 30 stray cats were processed using nested PCR and
      commercial immunochromatographic tests to diagnose infections. To evaluate the
      factors associated with FIV and/or FeLV in owned cats, a semi-structured
      interview was conducted with each owner about the animal's environment, and these
      data were subjected to unconditional logistic regression. The frequencies for
      owned cats were 6% (12/200) and 3% (6/200) for FIV and FeLV, respectively. No
      owned cat was positive for both viruses. Stray cats showed frequencies of 6.66%
      (2/30) and 0% (0/30) for FIV and FeLV, respectively. Contact with other cats and
      living in peri-urban areas were considered to be risk factors (P < 0.05) for FIV.
      We did not identify any factors associated with infections with FeLV. Our results
      confirm the presence of these two retroviruses in the region under study. Our use
      of different diagnostic techniques allowed us to determine the frequency of
      retroviruses in the feline population more accurately, particularly with regard
      to infections by FeLV, which have complex pathogenesis.

PMID- 28510254
TI  - Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK
      and JDP2 in NSC-34 cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects
      motor neurons and lacks an effective treatment. The disease pathogenesis has not
      been clarified at present. Pathological transactive response DNA-binding protein
      43 (TDP-43) plays an important role in the pathogenesis of ALS. Nuclear
      translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is
      found in a mutant TDP-43 transgenic cell model, but its downstream antioxidant
      enzyme expression is decreased. To elucidate the specific mechanism of Nrf2/ARE
      (antioxidant responsive element) signaling dysfunction, we constructed an ALS
      cell model with human mutant TDP-43 using the NSC-34 cell line to evaluate the
      impact of the TDP-43 mutation on the Nrf2/ARE pathway. We found the nuclear
      translocation of Nrf2, but the expression of total Nrf2, cytoplasmic Nrf2, and
      downstream phase II detoxifying enzyme (NQO1) was decreased in NSC-34 cells
      transfected with the TDP-43-M337V plasmid. Besides, TDP-43-M337V plasmid
      transfected NSC-34 cells were rounded with reduced neurites, shortened axons,
      increased levels of intracellular lipid peroxidation products, and decreased
      viability, which suggests that the TDP-43-M337V plasmid weakened the antioxidant
      capacity of NSC-34 cells and increased their susceptibility to oxidative damage.
      We further showed that expression of the MafK protein and the Jun dimerization
      protein 2 (JDP2) was reduced in TDP-43-M337V plasmid-transfected NSC-34 cells,
      which might cause accumulation of Nrf2 in nuclei but a decrease in NQO1
      expression. Taken together, our results confirmed that TDP-43-M337V impaired the
      Nrf2/ARE pathway by reducing the expression of MafK and JDP2 proteins, and
      provided information for further research on the molecular mechanisms of TDP-43
      M337V in ALS.

PMID- 28510255
TI  - Adaptability and stability of soybean cultivars for grain yield and seed quality.
AB  - This study aimed at verifying the adaptability and stability of soybean
      cultivars, considering the grain yield and quality of seeds, adopting univariate
      and multivariate approaches. The experiments were conducted in two crops, three
      environments, in 2013/2014 and 2014/2015 crop seasons, in the county of
      Inconfidentes, Lavras, and Patos de Minas, in the Minas Gerais State, Brazil. We
      evaluated 17 commercial soybean cultivars. For adaptability and stability
      evaluations, the Graphic and GGE biplot methods were employed. Previously, a
      selection index was estimated based on the sum of the standardized variables (Z
      index). The data relative to grain yield, mass of one thousand grain, uniformity
      test (sieve retention), and germination test were standardized (Zij) per
      cultivar. With the sum of Zij, we obtained the selection index for the four
      traits evaluated together. In the Graphic method evaluation, cultivars NA 7200 RR
      and CD 2737 RR presented the highest values for selection index Z. By the GGE
      biplot method, we verified that cultivar NA 7200 RR presented greater stability
      in both univariate evaluations, for grain yield, and for selection index Z.

PMID- 28510256
TI  - Interregional cytogenetic comparisons in Halichoeres and Thalassoma wrasses
      (Labridae) of coastal and insular regions of the southwestern Atlantic.
AB  - The distribution patterns of marine biodiversity are complex, resulting from
      vicariant events and species dispersion, as well as local ecological and adaptive
      conditions. Furthermore, the wide geographic distribution of some species may be
      hindered by biogeographical barriers that can interfere in the gene flow.
      Cytogenetic analyses in marine fishes, especially those involving populations in
      small remote insular environments, remain scarce. In the Western Atlantic,
      species of wrasses from the genera Halichoeres and Thalassoma occur in
      biogeographic arrangements that make it possible to analyze cytogenetic patterns
      between coastal and widely separated island populations. Species of these genera
      were punctually analyzed in some Atlantic regions. In this study, we compared
      several chromosomal features, such as karyotype macrostructure, heterochromatic
      patterns, patterns of base-specific fluorochromes, Ag-NORs, and 18S and 5S
      ribosomal sites in Thalassoma noronhanum, Halichoeres poeyi, and Halichoeres
      radiatus individuals from distinct coastal or insular regions of Atlantic.
      Notably, all of them are characterized by multiple 18S and 5S rDNA sites with
      syntenic arrangements in some chromosome pairs. Individuals of T. noronhanum
      (between the insular regions of Rocas Atoll and Fernando de Noronha Archipelago -
      FNA) and H. poeyi (coastal areas from Northeastern Brazil) show no detectable
      differences among their cytogenetic patterns. On the other hand, H. radiatus from
      FNA and Sao Pedro and Sao Paulo Archipelago exhibit differences in the frequency
      of rDNA sites that could suggest some level of population structuring between
      these insular regions. Interregional cytogenetic inventories of marine species
      with wide geographic distribution need to be rapidly expanded. These data will
      allow a better understanding of the level of chromosomal stability between vast
      oceanic spaces, which may be less than previously thought.

PMID- 28510257
TI  - Strategy for selection of soybean genotypes tolerant to drought during
      germination.
AB  - Water deficit is the main reason for instability in the context of soybean
      culture. The development of strategies for the selection of more tolerant
      genotypes is necessary. These strategies include the use of polyethylene glycol
      6000 solutions (PEG-6000) for conducting the germination test under conditions of
      water restriction. Thus, the objective of this study was to determine the osmotic
      potential and the main characteristics that promote the discrimination of soybean
      genotypes with regard to water stress tolerance during germination and the vigor
      test. Thirteen soybean cultivars were used. The seeds were allowed to germinate
      on sheets of germitest paper moistened in solution with PEG-6000, simulating
      different levels of water availability, which is expressed as osmotic potential
      (0.0, -0.2, -0.4, and -0.6 MPa). We assessed germination, length, and dry mass
      for seedlings and seeds, as well as reserve dynamics. Germination and variables
      related to the dynamics of reservation have great influence on the expression of
      variability in environments under stress. Among the different osmotic potentials,
      the -0.2 MPa was the most efficient for the expression of genetic variability
      among the cultivars. Conducting the germination test with PEG-6000 solution to 
      0.2 MPa was efficient for selecting soybean cultivars tolerant to water stress.
      This was accomplished by evaluating the percentage of germination, along with
      variables related to the dynamics of reservation.

PMID- 28510258
TI  - Diversity of plant growth-promoting bacteria associated with sugarcane.
AB  - The sugarcane (Saccharum spp) presents economic importance, mainly for tropical
      regions, being an important Brazilian commodity. However, this crop is strongly
      dependent on fertilizers, mainly nitrogen (N). This study assessed the plant
      growth-promoting bacteria (PGPB) associated with sugarcane that could be used as
      a potential inoculant to the crop. We evaluated the genetic diversity of PGPB in
      the plant tissue of sugarcane varieties (RB 867515, RB 1011, and RB 92579). The
      primer BOX-A1R was used to differentiate the similar isolated and further
      sequencing 16S rRNA ribosomal gene. The 16S rRNA gene showed the presence of
      seven different genera distributed into four groups, the genus Bacillus, followed
      by Paenibacillus (20%), Burkholderia (14%), Herbaspirillum (6%), Pseudomonas
      (6%), Methylobacterium (6%), and Brevibacillus (3%). The molecular
      characterization of endophytic isolates from sugarcane revealed a diversity of
      bacteria colonizing this plant, with a possible biotechnological potential to be
      used as inoculant and biofertilizers.

PMID- 28510259
TI  - 27th Meeting of the European Association for the Study of Diabetes Eye
      Complications Study Group (EASDec).
AB  - Abstracts will be available online on 25 May 2017.

PMID- 28510260
TI  - Markers of enteral adaptation in pediatric short bowel syndrome.
AB  - BACKGROUND: The aim of this study was to ascertain if prospective determination
      of specific gut hormones and growth factors could predict bowel adaptation in
      children with short bowel syndrome (SBS). METHODS: We studied independence from
      parenteral nutrition (PN) as the short-term result and discontinuation of enteral
      nutrition (EN) as the long-term result from a retrospective chart review of seven
      patients with SBS, who were managed in the absence of growth retardation. The
      correlation between increased number of enteral feeds or enteral nutrients and
      fasting serum gastrin, glucagon-like peptide 2 (GLP-2), citrulline, and D-amino
      acid oxidase (DAO) activity was analyzed. Five patients were weaned from PN, and
      two from EN. RESULTS: Fasting serum gastrin was significantly higher and serum
      GLP-2 lower in the PN-dependent patients than in the patients weaned from EN. The
      upper limit of fasting serum gastrin for PN independence and for EN independence
      was 300 and 200 pg/mL, respectively. The lower limit of fasting serum citrulline
      for PN independence was 15 MUmol/L. The relationship between serum citrulline and
      DAO and the course of bowel adaptation, however, was poor. CONCLUSIONS: Serum
      citrulline is a predictor of PN independence in children with SBS. Fasting serum
      gastrin and GLP-2 are indicators for adaptation of the residual intestine, but
      this was a small study and further larger prospective trials are required to
      confirm these results.

PMID- 28510261
TI  - Constraints on trait combinations explain climatic drivers of biodiversity: the
      importance of trait covariance in community assembly.
AB  - Trade-offs maintain diversity and structure communities along environmental
      gradients. Theory indicates that if covariance among functional traits sets a
      limit on the number of viable trait combinations in a given environment, then
      communities with strong multidimensional trait constraints should exhibit low
      species diversity. We tested this prediction in winter annual plant assemblages
      along an aridity gradient using multilevel structural equation modelling.
      Univariate and multivariate functional diversity measures were poorly explained
      by aridity, and were surprisingly poor predictors of community richness. By
      contrast, the covariance between maximum height and seed mass strengthened along
      the aridity gradient, and was strongly associated with richness declines.
      Community richness had a positive effect on local neighbourhood richness,
      indicating that climate effects on trait covariance indirectly influence
      diversity at local scales. We present clear empirical evidence that declines in
      species richness along gradients of environmental stress can be due to increasing
      constraints on multidimensional phenotypes.

PMID- 28510262
TI  - What is your diagnosis? Pancreatic aspirate from a cat.

PMID- 28510263
TI  - Reply.

PMID- 28510266
TI  - Look At That! Video Chat and Joint Visual Attention Development Among Babies and
      Toddlers.
AB  - Although many relatives use video chat to keep in touch with toddlers, key
      features of adult-toddler interaction like joint visual attention (JVA) may be
      compromised in this context. In this study, 25 families with a child between 6
      and 24 months were observed using video chat at home with geographically
      separated grandparents. We define two types of screen-mediated JVA (across- and
      within-screen) and report age-related increases in the babies' across-screen JVA
      initiations, and that family JVA usage was positively related to babies' overall
      attention during video calls. Babies today are immersed in a digital world where
      formative relationships are often mediated by a screen. Implications for both
      infant social development and developmental research are discussed.

PMID- 28510265
TI  - Severity and outcome of the norovirus infection in children after intestinal
      transplantation.
AB  - In immunocompromised patients, the NoV infection is prolonged and severe. We
      retrospectively studied the severity of the NoV infection in children after an
      ITx, the treatment, and the long-term evolution. Norovirus PCR in stools was
      positive for 19 children in 21 separate episodes. The infection was symptomatic
      in 18 cases. At diagnosis, the median weight loss was 5% (0-11) and the
      creatinine clearance was 75 mL/min/1.73 m2 (19-142). On 14 digestive biopsies,
      the pathological findings were non-specific with a constant mononuclear
      infiltration, showing signs of rejection in one case. Fifteen children in 17
      cases were hospitalized for a median duration of 41 days (0-119) with IV
      infusions for 33 days (0-120). The viral shedding lasted 78 days (20-360). Nine
      children with severe or prolonged diarrhea received intravenous IGs and four of
      them additional NTZ. On follow-up, five other children developed a rejection 12
      months (1-33) after NoV infection. Four uncontrolled rejections led to graft
      removal. Children mostly needed hospital admission and IV rehydration, but the
      symptoms upon presentation were moderate. Symptoms and shedding durations are
      prolonged as expected. The treatment efficacy cannot be assessed. The rejection
      induction by the NoV cannot be excluded.

PMID- 28510267
TI  - The Jack Wills crowd: towards a sociology of an elite subculture.
AB  - British sociologists have long been interested in youth sub-cultures. However
      British sociologists have tended to focus on working class subcultures and
      avoided engagement with exclusive sub-cultures of elite social groups. This
      article seeks to attend to this gap by examining the subculture of a British
      elite: ex-public school students at select universities in the UK in the twenty
      first century. This group consists of a relatively small group of young adults,
      aged between 18 and 23, who attended public schools, especially one of the nine
      Clarendon schools (Eton, Winchester, Westminster, St. Paul's, Merchant Taylor's,
      Shrewsbury, Rugby, Harrow and Charterhouse), and were students at a selective
      group of British universities, primarily Oxford and Cambridge, Durham, Bristol,
      Exeter, Bath, Manchester, St Andrews and Edinburgh. The article examines the way
      in which this group has reconfigured and re-constituted itself in the face of
      globalizing challenges. Specifically, it examines the way in which participation
      of ex-public school students in events run by and under the patronage of the high
      street retailing company, Jack Wills, has played a galvanising role for this
      group in the last decade. The Jack Wills crowd is an example of how some young
      adults form exclusive social networks and reproduce prevailing forms of
      privilege. The social networks built around the Jack Wills subculture is likely
      to provide them with advantages in the job market through a prodigious network of
      connections and patrons. The Jack Wills subculture potentially contributions to
      the socio-economic reproduction of the higher professional middle classes.

PMID- 28510268
TI  - Effect of intervention initiation timing of pulsed electromagnetic field on
      ovariectomy-induced osteoporosis in rats.
AB  - The aim of this study is to explore the effect of timing of initiation of pulsed
      electromagnetic field (PEMF) therapy on bone mass, microarchitecture, and
      biomechanical properties, and to investigate receptor activator of NF-kB (RANK)
      expression in ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats were
      randomly divided into two equal batches of three groups each (10 rats in each
      group). The first batch comprised of sham-operated (Sham-0 group), ovariectomized
      (OVX-0 group), and ovariectomized plus treated with PEMF starting from the day of
      OVX (Early PEMF group). The second batch comprised of sham-operated (Sham-12
      group), ovariectomized (OVX-12 group), and ovariectomized plus treated with PEMF
      starting 12 weeks after OVX (Late PEMF group). Rats (whole body) in the early and
      late PEMF groups were exposed to PEMF (3.8 mT peak, 8 Hz pulse burst repetition
      rate). After 12 weeks of PEMF therapy, Early PEMF prevented OVX-induced
      deterioration in bone mineral density (BMD) and mechanical properties in lumbar
      vertebral body and femur, and deterioration in bone microarchitecture in lumbar
      vertebral body and proximal tibia. Late PEMF intervention only inhibited
      deterioration of BMD, bone microarchitecture, and mechanical properties in lumbar
      vertebral body. Both early and late PEMF therapy suppressed RANK protein
      expression in OVX rats without a concomitant effect on RANK mRNA expression.
      These results demonstrate that timing of initiation of PEMF therapy plays an
      important role in achieving optimal beneficial effects. The specific PEMF
      parameters may exert these favorable biological responses, at least partially,
      via inhibition of protein expression of RANK. Bioelectromagnetics. 38:456-465,
      2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28510270
TI  - Mouse Fgf8-Cre-LacZ lineage analysis defines the territory of the postnatal
      mammalian isthmus.
AB  - The isthmus is recognized as the most rostral segment of the hindbrain in non
      mammalian vertebrates. In mammalian embryos, transient Fgf8 expression defines
      the developing isthmic region, lying between the midbrain and the first
      rhombomere, but there has been uncertainty about the existence of a distinct
      isthmic segment in postnatal mammals. We attempted to find if the region of early
      embryonic Fgf8 expression (which is considered to involve the entire extent of
      the prospective isthmus initially) might help to identify the boundaries of the
      isthmus in postnatal animals. By creating an Fgf8-Cre-LacZ lineage in mice, we
      were able to show that Fgf8-Cre reporter expression in postnatal mice is present
      in the same nuclei that characterize the isthmic region in birds. The 'signature'
      isthmic structures in birds include the trochlear nucleus, the dorsal raphe
      nucleus, the microcellular tegmental nuclei, the pedunculotegmental nucleus, the
      vermis of the cerebellum, rostral parts of the parabrachial complex and locus
      coeruleus, and the caudal parts of the substantia nigra and VTA. We found that
      all of these structures were labeled with the Fgf8-Cre reporter in the mouse
      brain, and we conclude that the isthmus is a distinct segment of the mammalian
      brain lying caudal to the midbrain and rostral to rhombomere 1 of the hindbrain.

PMID- 28510271
TI  - Application of Combination High-Throughput Phenotypic Screening and Target
      Identification Methods for the Discovery of Natural Product-Based Combination
      Drugs.
AB  - Modern drug discovery efforts have had mediocre success rates with increasing
      developmental costs, and this has encouraged pharmaceutical scientists to seek
      innovative approaches. Recently with the rise of the fields of systems biology
      and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm
      in drug discovery, with a focus on multiple targets and drug combinations for
      treating disease. Studies on the benefits of drug combinations lay the groundwork
      for a renewed focus on natural products in drug discovery. Natural products
      consist of a multitude of constituents that can act on a variety of targets in
      the body to induce pharmacodynamic responses that may together culminate in an
      additive or synergistic therapeutic effect. Although natural products cannot be
      patented, they can be used as starting points in the discovery of potent
      combination therapeutics. The optimal mix of bioactive ingredients in natural
      products can be determined via phenotypic screening. The targets and molecular
      mechanisms of action of these active ingredients can then be determined using
      chemical proteomics, and by implementing a reverse pharmacokinetics approach.
      This review article provides evidence supporting the potential benefits of
      natural product-based combination drugs, and summarizes drug discovery methods
      that can be applied to this class of drugs.

PMID- 28510272
TI  - Diabetes mellitus is associated with increased acute kidney injury and 1-year
      mortality after transcatheter aortic valve replacement: A meta-analysis.
AB  - BACKGROUND: Diabetes mellitus (DM) is associated with adverse outcomes after
      surgical aortic valve replacement. However, there are conflicting data on the
      impact of DM on outcomes of transcatheter aortic valve replacement (TAVR).
      HYPOTHESIS: DM is associated with poor outcomes after different cardiac
      procedures. Therefore, DM can also be associated with poor outcomes after TAVR.
      METHODS: We searched PubMed and Cochrane Central Register of Controlled Trials
      for studies that evaluated outcomes after TAVR and stratified at least 1 of the
      studied endpoints by DM status. The primary endpoint was all-cause mortality at 1
      year. Secondary endpoints were early (up to 30 days) mortality, acute kidney
      injury (AKI), cerebrovascular accident (CVA), major bleeding, and major vascular
      complications. Pooled odds ratio (OR) and 95% confidence interval (CI) were
      calculated using random effects models. RESULTS: We included 64 studies with a
      total of 38 686 patients. DM was associated with significantly higher 1-year
      mortality (OR: 1.14, 95% CI: 1.04-1.26, P = 0.008) and periprocedural AKI (OR:
      1.28, 95% CI: 1.08-1.52, P = 0.004). On the other hand, there were no significant
      differences between diabetics and nondiabetics in early mortality, CVAs, major
      bleeding, or major vascular complications. CONCLUSIONS: DM is associated with
      increased 1-year mortality and periprocedural AKI in patients undergoing TAVR.
      The results of this study suggest that DM is a predictor of adverse outcomes in
      patients undergoing TAVR.

PMID- 28510273
TI  - Manganese-Catalyzed Sustainable Synthesis of Pyrroles from Alcohols and Amino
      Alcohols.
AB  - The development of reactions that convert alcohols into important chemical
      compounds saves our fossil carbon resources as alcohols can be obtained from
      indigestible biomass such as lignocellulose. The conservation of our rare noble
      metals is of similar importance, and their replacement by abundantly available
      transition metals, such as Mn, Fe, or Co (base or nonprecious metals), in key
      technologies such as catalysis is a promising option. Herein, we report on the
      first base-metal-catalyzed synthesis of pyrroles from alcohols and amino
      alcohols. The most efficient catalysts are Mn complexes stabilized by PN5 P
      ligands whereas related Fe and Co complexes are inactive. The reaction proceeds
      under mild conditions at catalyst loadings as low as 0.5 mol %, and has a broad
      scope and attractive functional-group tolerance. These findings may inspire
      others to use Mn catalysts to replace Ir or Ru complexes in challenging
      dehydrogenation reactions.

PMID- 28510269
TI  - Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in
      prostate-derived stromal cells.
AB  - The reciprocal communication between cancer cells and their microenvironment is
      critical in cancer progression. Although involvement of cancer-associated
      fibroblasts (CAF) in cancer progression is long established, the molecular
      mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly
      understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes
      CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of
      premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared
      to normal prostate epithelia, especially at the peristromal interface. KLK4
      induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line,
      including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4
      activated protease-activated receptor-1 in WPMY1 cells increasing expression of
      several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer
      progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome
      changes, which in turn stimulated HUVEC cell proliferation that could be blocked
      by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of
      WPMY1 cells were also differentially expressed between patient-derived CAFs
      compared to matched nonmalignant fibroblasts and were further increased by KLK4
      treatment. Taken together, we propose that epithelial-derived KLK4 promotes
      tumour progression by actively promoting CAF differentiation in the prostate
      stromal microenvironment.

PMID- 28510274
TI  - The effect of prazosin on outcome in feline urethral obstruction.
AB  - OBJECTIVE: To determine whether prazosin administration following urethral
      obstruction (UO) reduces the risk for recurrent urethral obstruction (rUO) or
      lower urinary tract signs, and to document adverse effects associated with
      prazosin use in cats. DESIGN: Double-blinded, prospective, interventional study.
      SETTING: University teaching hospital. ANIMALS: A population of 47 consecutive
      male cats with UO not associated with urinary tract calculi >2 mm in diameter.
      INTERVENTIONS: Cats were randomized to receive either prazosin (0.25 mg/cat PO q
      12 h, n = 27) or placebo (n = 20) for 1 month following UO. MEASUREMENTS AND MAIN
      RESULTS: Cats were monitored for rUO, severity of lower urinary tract signs, and
      medication adverse effects during hospitalization and through weekly
      conversations with the owner during the 1- month study period and once more at 6
      months following discharge. There was no difference in the rUO rate among cats
      that received prazosin or placebo prior to hospital discharge (2/26 (7%) versus
      1/19 (5%), P = 1.00), during the 1- month medication period (4/26 (15%) versus
      3/18 (17%), P = 0.776), or at 6 months following treatment for UO (7/19 (37%)
      versus 4/13 (31%), P = 0.811). There was no difference in the severity of lower
      urinary tract signs reported by the owners at the 1-, 2-, 3-, or 4-week follow-up
      periods among the cats in either group (P = 0.62, 0.68, 0.33, 1.00,
      respectively). Reported adverse effects from prazosin administration included
      lethargy, ptyalism, diarrhea, anorexia, and malodorous stool. CONCLUSIONS:
      Although our study results failed to find a difference in the incidence of rUO
      and severity of lower urinary tract signs among cats receiving prazosin and those
      receiving placebo, these study results should be interpreted cautiously as our
      study was underpowered to identify such differences. Larger placebo-controlled,
      prospective studies are needed to determine the clinical utility of prazosin in
      prevention of rUO.

PMID- 28510275
TI  - Single cell transcriptome profiling of developing chick retinal cells.
AB  - The vertebrate retina is a specialized photosensitive tissue comprised of six
      neuronal and one glial cell types, each of which develops in prescribed
      proportions at overlapping timepoints from a common progenitor pool. While each
      of these cells has a specific function contributing to proper vision in the
      mature animal, their differential representation in the retina as well as the
      presence of distinctive cellular subtypes makes identifying the transcriptomic
      signatures that lead to each retinal cell's fate determination and development
      challenging. We have analyzed transcriptomes from individual cells isolated from
      the chick retina throughout retinogenesis. While we focused our efforts on the
      retinal ganglion cells, our transcriptomes of developing chick cells also
      contained representation from multiple retinal cell types, including
      photoreceptors and interneurons at different stages of development. Most
      interesting was the identification of transcriptomes from individual mixed
      lineage progenitor cells in the chick as these cells offer a window into the cell
      fate decision-making process. Taken together, these data sets will enable us to
      uncover the most critical genes acting in the steps of cell fate determination
      and early differentiation of various retinal cell types.

PMID- 28510276
TI  - Canine reticulocyte hemoglobin content (RET-He) in different types of iron
      deficient erythropoiesis.
AB  - BACKGROUND: Reticulocyte hemoglobin content (RET-He) is a diagnostic marker for
      iron deficiency (ID) in people and dogs. OBJECTIVES: The aim of our study was to
      evaluate the clinical utility of RET-He in the diagnosis of different causes of
      iron-deficient erythropoiesis (IDE). METHODS: Canine CBCs were separated into 2
      groups according to RET-He values, < 20.9 pg or >= 20.9 pg. Erythrocyte and
      reticulocyte variables were compared between dogs with decreased and normal RET
      He values. Additional data for a subgroup of dogs were collected, and dogs with
      low RET-He values were categorized as having ID, inflammatory disorders (INFL),
      portosystemic shunt (PSS), miscellaneous diseases (MISC), or combinations of
      these diseases (ID+INFL, ID+PSS). Hematologic variables were compared between
      dogs of the different disease groups. RESULTS: Overall, 10.3% (1084/10,553) of
      canine CBCs showed decreased RET-He values. Significant differences between dogs
      with decreased and normal RET-He values were found for all erythrocyte and
      reticulocyte variables. The majority (68.9%, 747/1084) of dogs with low RET-He
      values was anemic; 28.9% (216/747) of those anemic dogs had microcytosis and
      hypochromasia. In the subgroup of dogs, 8.9% (205/2306) had low RET-He values.
      According to their diagnosed diseases, anemic dogs (138/205) could be categorized
      as ID (17/138; 12.3%), INFL (16/138; 11.6%), PSS (30/138; 21.7%), ID+INFL
      (63/138; 45.7%), ID+PSS (8/138; 5.8%), and MISC (4/138; 2.9%). Distribution in
      nonanemic dogs (67/205) was similar, except for a lower number of dogs with PSS.
      CONCLUSIONS: Low RET-He values indicate IDE even in dogs with other CBC variables
      within the RIs.

PMID- 28510277
TI  - Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on
      human blood lymphocytes.
AB  - The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate
      (CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human
      toxicity studies. Using biochemical and flow cytometry assessments, we
      demonstrated that addition of CHG at 1 MUM concentration to human blood
      lymphocytes induced cytotoxicity following 6 h. The CHG-induced cytotoxicity on
      human blood lymphocytes was associated with intracellular reactive oxygen species
      generation, mitochondrial membrane potential collapse, lysosomal membrane injury,
      lipid peroxidation, and depletion of glutathione. According to our results, CHG
      triggers oxidative stress and organelles damages in lymphocytes which are
      important cells in defense against foreign agents. Finally our findings suggest
      that using of antioxidants and mitochondrial/lysosomal protective agents could be
      of benefit for the people in the exposure with CHG.

PMID- 28510279
TI  - 1-Substituted 2-Azaspiro[3.3]heptanes: Overlooked Motifs for Drug Discovery.
AB  - The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs),
      however, their spirocyclic analogues remain unknown. Described here is the
      synthesis of spirocyclic analogues for 2-substituted piperidines and a
      demonstration of their validation in drug discovery.

PMID- 28510278
TI  - TFG-MET fusion in an infantile spindle cell sarcoma with neural features.
AB  - An increasing number of congenital and infantile sarcomas displaying a primitive,
      monomorphic spindle cell phenotype have been characterized to harbor recurrent
      gene fusions, including infantile fibrosarcoma and congenital spindle cell
      rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a
      large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which
      revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The
      tumor resembled the morphology of an infantile fibrosarcoma with both fascicular
      and patternless growth, however, it expressed strong S100 protein
      immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression.
      Although this immunoprofile suggested partial neural/neuroectodermal
      differentiation, overall features were unusual and did not fit into any known
      tumor types (cellular schwannoma, MPNST), raising the possibility of a novel
      pathologic entity. The TFG-MET gene fusion expands the genetic spectrum
      implicated in the pathogenesis of congenital spindle cell sarcomas, with yet
      another example of kinase oncogenic activation through chromosomal translocation.
      The discovery of this new fusion is significant since the resulting MET
      activation can potentially be inhibited by targeted therapy, as MET inhibitors
      are presently available in clinical trials.

PMID- 28510281
TI  - CuI/Oxalic Diamide-Catalyzed Cross-Coupling of Thiols with Aryl Bromides and
      Chlorides.
AB  - We report a general copper-catalyzed cross-coupling of thiols with aryl halides
      by using N-aryl-N'-alkyl oxalic diamide (L3) or N,N'-dialkyl oxalic diamide (L5)
      as the ligand. Both aryl and alkyl thiols can be coupled with unactivated aryl
      bromides and chlorides to give the desired products in good yields. Furthermore,
      this system features a broad substrate scope and good tolerance of functional
      groups. Importantly, the oxalic diamides are stable and can be prepared easily
      from commercially available and cheap starting materials.

PMID- 28510280
TI  - Modeling the Iatrogenic Pancreatic Cancer Risk After Islet Autotransplantation in
      Mouse.
AB  - Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk
      of islet autotransplantation performed after pancreatectomy. To model this risk,
      islets and/or pancreatic exocrine clusters obtained from a genetically engineered
      mouse model for pancreatic ductal adenocarcinoma (the LSL-KrasG12D/+ ;LSL
      Trp53R172H/+ ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein
      in syngeneic wild type (WT) severely diabetic recipients in the following
      treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal
      to 250 islet equivalents (IEQs); group B (n = 12) received 250 WT IEQs mixed with
      KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQs,
      and group D (n = 7) received 250 WT IEQs. The incidence of hepatic metastasis was
      assessed by magnetic resonance imaging and histology over the 13 months of follow
      up. Overall survival was not different in the four groups. No mice developed
      liver metastases during the follow-up. Two mice developed spontaneous tumors: a
      liver hepatocellular tumor in group A and a malignant lymphoma in group D. Islets
      and/or exocrine clusters obtained by KPC mouse, a model that develops pancreatic
      cancer with 100% penetrance, do not retain the same risk of tumor development
      when transplanted via the portal vein in a syngeneic diabetic recipient.

PMID- 28510282
TI  - Cytologic features of a feline inductive odontogenic tumor.
AB  - The feline inductive odontogenic tumor (FIOT) is a rare entity among oral tumors
      in cats, the cytologic features of which are not well characterized but may prove
      useful. A fine-needle aspiration biopsy was performed on the right mandible
      between the permanent canine (404) and permanent fourth premolar (408) of an 8
      month-old female mongrel cat. Cytologic smears showed epithelial cells and
      occasional spindle cells with extracellular homogenous acidophilic material in a
      hematic background. The initial diagnosis of benign tumor was confirmed by
      histopathologic examination of the biopsy specimen. This report describes the
      cytologic findings in a case of FIOT.

PMID- 28510283
TI  - Ca2+ -Cl- Association in Water Revisited: the Role of Cation Hydration.
AB  - We investigate the dissociation of a Ca2+ -Cl- pair in water using classical
      molecular dynamics simulations with a polarizable interaction potential,
      parameterized from ab initio calculations. By computing the potential of mean
      force as a function not only of the interionic distance but also of the
      coordination numbers by water molecules, we show that it is necessary to use a
      collective variable describing the cation hydration in order to capture the
      dissociation mechanism. In the contact ion pair, the Ca2+ cation has a first
      coordination sphere containing 5 or 6 water molecules. The minimum free-energy
      path for dissociation involves a two-step process: First one or two additional
      water molecules enter the cation coordination shell, increasing the coordination
      number up to 7 with an almost fixed interionic distance. Then the dissociation of
      the ionic pair occurs at this fixed coordination number.

PMID- 28510284
TI  - Tricyanomethane and Its Ketenimine Tautomer: Generation from Different Precursors
      and Analysis in Solution, Argon Matrix, and as a Single Crystal.
AB  - Solutions of azidomethylidenemalononitrile were photolyzed at low temperatures to
      produce the corresponding 2H-azirine and tricyanomethane, which were analyzed by
      low-temperature NMR spectroscopy. The latter product was also observed after
      short thermolysis of the azide precursor in solution whereas irradiation of the
      azide isolated in an argon matrix did not lead to tricyanomethane, but to
      unequivocal detection of the tautomeric ketenimine by IR spectroscopy for the
      first time. When the long-known "aquoethereal" greenish phase generated from
      potassium tricyanomethanide, dilute sulfuric acid, and diethyl ether was rapidly
      evaporated and sublimed, a mixture of hydronium tricyanomethanide and
      tricyanomethane was formed instead of the previously claimed ketenimine tautomer.
      Under special conditions of sublimation, single crystals of tricyanomethane could
      be isolated, which enabled the analysis of the molecular structure by X-ray
      diffraction.

PMID- 28510285
TI  - Influence of quality of recovery on patient satisfaction with anaesthesia and
      surgery: a prospective observational cohort study.
AB  - Patient satisfaction and quality of recovery are important measures of quality.
      Whether, and to what extent, patient satisfaction is influenced by quality of
      recovery, however, is not clear. The aim of this study was to evaluate the
      additional influence of quality of recovery on total patient satisfaction with
      anaesthesia and surgery. In this prospective cohort study, we used a validated
      quality of recovery questionnaire and a multi-item patient satisfaction
      questionnaire. Patients completed the quality of recovery questionnaire pre
      operatively and 24 h postoperatively. One to two weeks after discharge, a third
      quality of recovery questionnaire was sent out, together with the patient
      satisfaction questionnaire. If no response was received after 2 weeks, a reminder
      containing the quality of recovery and the satisfaction questionnaire were
      mailed. Seven hundred and thirty-four patients were consecutively assessed for
      eligibility. Five hundred and seventy-nine patients completed at least one
      questionnaire (recruitment rate 79%). Four hundred and sixty-seven patients (81%)
      completed all four questionnaires. The total satisfaction score was high, with a
      mean (SD) of 94.6 (10.7) on a 0-100 scale. Correlation analysis between quality
      of recovery and total patient satisfaction showed correlations of 0.2-0.3.
      Testing different aspects of quality of recovery in models already containing the
      significant factors of patient satisfaction did not improve the model fit
      markedly. We conclude that quality of recovery has only a marginal additional
      effect on total patient satisfaction with anaesthesia and surgery.

PMID- 28510286
TI  - An Enyne Cope Rearrangement Enables Polycycloalkane Synthesis from Readily
      Available Starting Materials.
AB  - Cyclohexanone-derived Knoevenagel adducts (cyclohexylidenemalononitriles) and two
      different propargyl electrophiles serve as carbon sources for assembling diverse
      6/7/5 tricycloalkanes, a common terpenoid framework. The sequence involves three
      unique reactions: 1) deconjugative propargylation, 2) one-pot enyne Cope
      rearrangement/deconjugative propargylation, and 3) an allenic Pauson-Khand
      reaction.

PMID- 28510287
TI  - A Dual Palladium and Copper Hydride Catalyzed Approach for Alkyl-Aryl Cross
      Coupling of Aryl Halides and Olefins.
AB  - We report an efficient means of sp2 -sp3 cross coupling for a variety of terminal
      monosubstituted olefins with aryl electrophiles using Pd and CuH catalysis. In
      addition to its applicability to a range of aryl bromide substrates, this process
      was also suitable for electron-deficient aryl chlorides, furnishing higher yields
      than the corresponding aryl bromides in these cases. The optimized protocol does
      not require the use of a glovebox and employs air-stable Cu and Pd complexes as
      precatalysts. A reaction on 10 mmol scale further highlighted the practical
      utility of this protocol. Employing a similar protocol, a series of cyclic
      alkenes were also examined. Cyclopentene was shown to undergo efficient coupling
      under these conditions. Lastly, deuterium-labeling studies indicate that
      deuterium scrambling does not take place in this sp2 -sp3 cross coupling,
      implying that beta-hydride elimination is not a significant process in this
      transformation.

PMID- 28510288
TI  - The Relationship of Physiopsychosocial Factors and Spiritual Well-Being in
      Elderly Residents: Implications for Evidence-Based Practice.
AB  - BACKGROUND: Older adults in residential settings frequently suffer from
      functional decline, mental illness, and social isolation, which make them more
      vulnerable to spiritual distress. However, empirical evidence of the
      interrelationships between physiopsychosocial variables and spiritual well-being
      are still lacking, limiting the application of the biopsychosocial-spiritual
      model in institutional healthcare practice. AIMS: To explain the mechanisms by
      which these variables are linked, this cross-sectional study tested a causal
      model of predictors of spiritual well-being among 377 institutionalized older
      adults with disability using a structural equation modeling approach. METHODS:
      The primary variables in the hypothesized model were measured using the Barthel
      Index for functional ability, the Geriatric Depression Scale-short form for
      depression, the Personal Resources Questionnaire 85-Part 2 for perceived social
      support, and the Spiritual Well-Being Scale for spiritual well-being. RESULTS:
      The model fit indices suggest that the hypothesized model had a reasonably
      adequate model fit (chi2 = 12.18, df = 6, p = .07, goodness-of-fitness index
      [GFI] = 0.99, adjusted GIF index [AGFI] = 0.93, nonnormed fit index [NFI] = 0.99,
      comparative fit index [CFI] = 0.99). In this study, perceived social support and
      depression directly affected spiritual well-being, and functional ability
      indirectly affected spiritual well-being via perceived social support or
      depression. In addition, functional ability influenced perceived social support
      directly, which in turn influenced depression and ultimately influenced spiritual
      well-being. DISCUSSION: This study results confirm the effect of
      physiopsychosocial factors on institutionalized older adults' spiritual well
      being. However, the presence and level of functional disability do not
      necessarily influence spiritual well-being in late life unless it is disruptive
      to social relationships and is thus bound to lead to low perceived social support
      and the onset of depression. LINKING EVIDENCE TO ACTION: The findings address the
      fact that the practice of spirituality is multidimensional and multileveled.
      Psychosocial interventions for institutionalized elders with disabilities should
      focus on increasing nurse-patient interaction and providing access to meaningful
      social activities to improve mental health and spiritual well-being.

PMID- 28510289
TI  - Genome organization during the cell cycle: unity in division.
AB  - During the cell cycle, the genome must undergo dramatic changes in structure,
      from a decondensed, yet highly organized interphase structure to a condensed,
      generic mitotic chromosome and then back again. For faithful cell division, the
      genome must be replicated and chromosomes and sister chromatids physically
      segregated from one another. Throughout these processes, there is feedback and
      tension between the information-storing role and the physical properties of
      chromosomes. With a combination of recent techniques in fluorescence microscopy,
      chromosome conformation capture (Hi-C), biophysical experiments, and
      computational modeling, we can now attribute mechanisms to many long-observed
      features of chromosome structure changes during cell division. Apparent conflicts
      that arise when integrating the concepts from these different proposed mechanisms
      emphasize that orchestrating chromosome organization during cell division
      requires a complex system of factors rather than a simple pathway. Cell division
      is both essential for and threatening to proper genome organization. As
      interphase three-dimensional (3D) genome structure is quite static at a global
      level, cell division provides an important window of opportunity to make
      substantial changes in 3D genome organization in daughter cells, allowing for
      proper differentiation and development. Mistakes in the process of chromosome
      condensation or rebuilding the structure after mitosis can lead to diseases such
      as cancer, premature aging, and neurodegeneration. WIREs Syst Biol Med 2017,
      9:e1389. doi: 10.1002/wsbm.1389 For further resources related to this article,
      please visit the WIREs website.

PMID- 28510290
TI  - Retrospective evaluation of the impact of early enteral nutrition on clinical
      outcomes in dogs with pancreatitis: 34 cases (2010-2013).
AB  - OBJECTIVE: To evaluate the effect of early enteral nutritional therapy on time to
      return to voluntary intake, maximum food consumption, incidence of
      gastrointestinal intolerance (GI), and total hospitalization time for dogs with
      acute pancreatitis. DESIGN AND SETTING: Retrospective analysis of dogs with
      pancreatitis at a veterinary teaching hospital between 2010 and 2013. ANIMALS:
      Thirty-four client-owned dogs diagnosed with acute or acute-on-chronic
      pancreatitis. PROCEDURES AND INTERVENTIONS: Medical records of dogs evaluated for
      inappetence, anorexia, and GI for which a diagnosis of pancreatitis was recorded
      were reviewed. The time to initiation of food offerings since hospitalization
      were recorded in addition to signalment, historical medical conditions, chief
      complaint, physical examination findings, diagnostic results, treatments
      provided, timing of food offering (within 48 h of hospitalization, early feeding
      group (EFG) versus delayed feeding group (DFG), diet therapy (low fat versus high
      fat), caloric intake (% resting energy requirement), incidence of GI (%), and
      length of hospitalization (LOH) (days). A Clinical Severity Index Score (CSIS)
      was determined for each patient. MEASUREMENTS AND MAIN RESULTS: Dogs in the EFG
      demonstrated a decreased time to return of voluntary intake (2.1 days, EFG versus
      2.7 days, DFG; P = 0.05) and time (days) to maximum intake (3, EFG versus 3.4
      DFG) as compared to the DFG dogs. The DFG exhibited more GI versus EFG
      irrespective of CSIS grouping (60% versus 26%, P = 0.04). A CSIS >= 7 was
      associated with prolonged LOH (P = 0.004); however, time to initiation of feeding
      and diet selection did not impact LOH (P = 0.8). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results of the study suggested that feeding within 48 hours of
      hospitalization for canine pancreatitis has a positive impact on return to
      voluntary intake and decreases the frequency of GI in these patients, independent
      of CSIS. The traditional protocol of withholding food during hospitalization may
      not be necessary nor yield the most benefit for patient recovery; subsequently
      early enteral refeeding should be considered.

PMID- 28510292
TI  - Enhanced Photoelectrochemical Activity by Autologous Cd/CdO/CdS Heterojunction
      Photoanodes with High Conductivity and Separation Efficiency.
AB  - The development for hydrogen from solar energy has attracted great attention due
      to the global demand for clean, environmentally friendly energy. Herein,
      autologous Cd/CdO/CdS heterojunctions were prepared in a carefully controlled
      process with metallic Cd as the inner layer and CdO as the interlayer. Further
      research revealed that the transportation and separation of photogenerated pairs
      were enhanced due to low resistance of the Cd inner layer and the type II CdO/CdS
      heterojunction. As a result, the optimized Cd/CdO/CdS heterojunction photoanode
      showed outstanding and long-term photoelectrochemical activity for water
      splitting, with a current density of 3.52 mA cm-2 , or a benchmark specific
      hydrogen production rate of 1.65 MUmol cm-2  min-1 at -0.3 V versus Ag/AgCl, by
      using the environmental pollutants of sulfide and sulfite as sacrificial agents.

PMID- 28510293
TI  - A test for Y-linked additive and epistatic effects on surviving bacterial
      infections in Drosophila melanogaster.
AB  - Y- and W-chromosomes offer a theoretically powerful way for sexual dimorphism to
      evolve. Consistent with this possibility, Drosophila melanogaster Y-chromosomes
      can influence gene regulation throughout the genome; particularly immune-related
      genes. In order for Y-linked regulatory variation (YRV) to contribute to adaptive
      evolution it must be comprised of additive genetic variance, such that variable
      Ys induce consistent phenotypic effects within the local gene pool. We assessed
      the potential for Y-chromosomes to adaptively shape gram-negative and gram
      positive bacterial defence by introgressing Ys across multiple genetic haplotypes
      from the same population. We found no Y-linked additive effects on immune
      phenotypes, suggesting a restricted role for the Y to facilitate dimorphic
      evolution. We did find, however, a large magnitude Y by background interaction
      that induced rank order reversals of Y-effects across the backgrounds (i.e. sign
      epistasis). Thus, Y-chromosome effects appeared consistent within backgrounds,
      but highly variable among backgrounds. This large sign epistatic effect could
      constrain monomorphic selection in both sexes, considering that autosomal alleles
      under selection must spend half of their time in a male background where relative
      fitness values are altered. If the pattern described here is consistent for other
      traits or within other XY (or ZW) systems, then YRV may represent a universal
      constraint to autosomal trait evolution.

PMID- 28510294
TI  - Dual photon microscopy based quantitation of fibrosis-related parameters (q-FP)
      to model disease progression in steatohepatitis: Methodological issues.

PMID- 28510291
TI  - Associations between RNA splicing regulatory variants of stemness-related genes
      and racial disparities in susceptibility to prostate cancer.
AB  - Evidence suggests that cells with a stemness phenotype play a pivotal role in
      oncogenesis, and prostate cells exhibiting this phenotype have been identified.
      We used two genome-wide association study (GWAS) datasets of African descendants,
      from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana
      Prostate Study, and two GWAS datasets of non-Hispanic whites, from the Prostate,
      Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and
      Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between
      genetic variants of stemness-related genes and racial disparities in
      susceptibility to prostate cancer. We evaluated associations of single-nucleotide
      polymorphisms (SNPs) in 25 stemness-related genes with prostate cancer risk in
      1,609 cases and 2,550 controls of non-Hispanic whites (4,934 SNPs) and 1,144
      cases and 1,116 controls of African descendants (5,448 SNPs) with correction by
      false discovery rate <=0.2. We identified 32 SNPs in five genes (TP63, ALDH1A1,
      WNT1, MET and EGFR) that were significantly associated with prostate cancer risk,
      of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs
      showed heterogeneity in susceptibility between these two racial groups. In
      addition, 13 SNPs in MET and one in ALDH1A1 were found only in African
      descendants. The in silico bioinformatics analyses revealed that EGFR rs2072454
      and SNPs in linkage with the identified SNPs in MET and ALDH1A1 (r2  > 0.6) were
      predicted to regulate RNA splicing. These variants may serve as novel biomarkers
      for racial disparities in prostate cancer risk.

PMID- 28510295
TI  - Scandium-Mediated Formation of a Bis(tetrahydropentalene).
AB  - The reactivity of Li[Sc(COT'')2 ] (1; COT''=1,4
      bis(trimethylsilyl)cyclooctatetraenyl) towards CoCl2 is considerably different
      from that of related lanthanide triple-decker sandwich complexes. In addition to
      the expected triple-decker complex Sc2 (COT'')3 (2), the complex Sc2 {MU
      BTHP}(COT'')2 (3) is formed, which comprises the novel BTHP2- ligand (BTHP2-
      =bis(3,5-bis(trimethylsilyl)-1,3a,6,6a-tetrahydropentalene-1-yl)diide or bis(2,7
      bis(trimethylsilyl)bicyclo[3.3.0]octa-2,7-dien-4-yl)diide, C16 H10 (SiMe3 )42- ).
      The formation of 3 is likely facilitated by the fact that scandium prefers eta8
      ,eta3  coordination rather than highly symmetric eta8 ,eta8  coordination, and
      the eta3 -coordinated COT'' ligand in 1 is activated owing to a loss of
      aromaticity. Acid hydrolysis of 3 leads to air-stable H2 BTHP (4).

PMID- 28510296
TI  - Pharmacokinetics and Safety of Single-Dose Inhaled Loxapine in Children and
      Adolescents.
AB  - This multisite open-label study sought to characterize the pharmacokinetics and
      safety of a single dose of inhaled loxapine in children and adolescents. Loxapine
      powder for oral inhalation was administered via a single-use handheld drug device
      to children and adolescents (aged 10-17 years) with any condition warranting
      chronic antipsychotic use. Patients were dosed according to body weight and
      cohort (<50 kg [n = 15], 2.5 or 5 mg; >=50 kg [n = 15], 5 or 10 mg); the first 6
      patients (cohort 1) enrolled in each weight group received the lower dose.
      Patients were enrolled in the higher-dose group (cohort 2) after an interim
      pharmacokinetic and safety analysis of data from cohort 1. Blood samples were
      collected for 48 hours after dosing to determine the pharmacokinetic profile of
      loxapine and its metabolites. Safety was assessed using adverse event (AE),
      laboratory value, physical/neurologic examination, vital sign, electrocardiogram,
      suicidality, and extrapyramidal symptom assessment. Thirty patients were enrolled
      and evaluable for pharmacokinetics. Loxapine plasma concentrations peaked by 2 to
      5 minutes in most patients; systemic exposure increased with dose in both weight
      subgroups. Loxapine terminal elimination half-life was ~13 to 17 hours. The most
      common AEs were sedation and dysgeusia. Sedation was severe in 1 patient in the
      <50-kg group (2.5-mg dose) and 1 patient in the >=50-kg group (5-mg dose). No AEs
      indicative of bronchospasm or other serious AEs were reported. Inhaled loxapine
      was rapidly absorbed and generally well tolerated in pediatric patients; no new
      safety signals were observed.

PMID- 28510298
TI  - Drugs for Children.
AB  - The "Therapeutic Orphan" status of children is gradually improving, but our
      efforts to eliminate off-label/off-evidence use must be sustained for safer and
      more effective pediatric drug therapy. This is even more important in resource
      scarce settings, because of the increasing child population in those regions. The
      juncture of pediatric pharmacology and global child health represents an emerging
      field of clinical pharmacology illuminating a crucial societal need on a global
      scale.

PMID- 28510297
TI  - Evaluation of the Safety of Drugs and Biological Products Used During Lactation:
      Workshop Summary.
AB  - This report serves as a summary of a 2-day public workshop sponsored by the US
      Food and Drug Administration (FDA) to discuss the safety of drugs and biological
      products used during lactation. The aim of the workshop was to provide a forum to
      discuss the collection of data to inform the potential risks to breastfed infants
      with maternal use of medications during lactation. Discussions included the
      review of current approaches to collect data on medications used during
      lactation, and the considerations for future approaches to design and guide
      clinical lactation studies. This workshop is part of continuing efforts to raise
      the awareness of the public for women who choose to breastfeed their infants.

PMID- 28510302
TI  - Association study of genetic variation in DNA repair pathway genes and risk of
      basal cell carcinoma.
AB  - DNA repair plays a critical role in protecting the genome from ultraviolet
      radiation and maintaining the genomic integrity of cells. Genetic variants in DNA
      repair-related genes can influence an individual's DNA repair capacity, which may
      be related to the risk of developing basal cell carcinoma (BCC). We
      comprehensively assessed the associations of 2,965 independent single-nucleotide
      polymorphisms (SNPs) across 165 DNA repair pathway genes with BCC risk in a
      genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054
      controls from two data sets. After multiple testing corrections, we identified
      three SNPs (rs2805831 upstream of XPA: OR = 0.93, P = 1.35 * 10-6 ; rs659857 in
      exon of MUS81: OR = 1.06, P = 3.09 * 10-6 and rs57343616 in 3' UTR of NABP2: OR =
      1.11, P = 6.47 * 10-6 ) as significantly associated with BCC risk in meta
      analysis, and all of them were nominally significant in both data sets.
      Furthermore, rs659857 [T] was significantly associated with decreased expression
      of MUS81 mRNA in the expression quantitative trait locus (eQTL) analysis. Our
      findings suggest that the inherited common variation in three DNA repair genes
      XPA, MUS81 and NABP2-may be involved in the development of BCC. To our knowledge,
      our study is the first report thoroughly examining the effects of SNPs across DNA
      repair pathway genes on BCC risk based on a genome-wide association meta
      analysis.

PMID- 28510304
TI  - Flip-Flop Phenomenon in Epidural Sufentanil Pharmacokinetics: A Population Study
      in Children and Infants.
AB  - The aims of this study were to develop a population pharmacokinetic model of
      sufentanil coadministered with 0.2% ropivacaine as an epidural infusion in
      infants and describe the sufentanil absorption profile from epidural space. Data
      from 2 previously published studies were merged for analysis-20 infants aged 3-36
      months receiving sufentanil as an epidural infusion and 41 children 0-17 years
      old receiving sufentanil as a long-term intravenous infusion. A population
      nonlinear mixed-effects model was built in NONMEM. Sufentanil pharmacokinetics
      were described by a 2-compartment model with first-order absorption. The effect
      of body size on all volume and clearance parameters was included in the model
      according to allometric scaling with theoretical exponents. The maturation
      process of metabolic clearance was described by the Hill model. During the model
      building process the population was divided into 2 fractions with different
      typical values of metabolic clearance (CL1 and CL2). The typical values of
      systemic clearance scaled to a 70-kg patient for the 2 subpopulations were CL1 =
      52.6 L/h and CL2 = 158 L/h. The parameters of the Hill function were 54.9 weeks
      for the postmenstrual age of 50% clearance maturation and 0.802 for the Hill
      coefficient. The typical values of distribution clearance and volumes of the
      central and peripheral compartments for a patient with a weight of 70 kg were Q =
      40.5 L/h, VC = 7.63 L, and VT = 473 L, respectively. The value of the absorption
      rate constant from the epidural space was 0.0459/h, which suggests flip-flop
      pharmacokinetics of sufentanil after epidural administration.

PMID- 28510303
TI  - A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and
      Dimeric Adapter Protein 14-3-3.
AB  - Interactions between proteins frequently involve recognition sequences based on
      multivalent binding events. Dimeric 14-3-3 adapter proteins are a prominent
      example and typically bind partner proteins in a phosphorylation-dependent mono-
      or bivalent manner. Herein we describe the development of a cucurbit[8]uril (Q8)
      based supramolecular system, which in conjunction with the 14-3-3 protein dimer
      acts as a binary and bivalent protein assembly platform. We fused the
      phenylalanine-glycine-glycine (FGG) tripeptide motif to the N-terminus of the 14
      3-3-binding epitope of the estrogen receptor alpha (ERalpha) for selective
      binding to Q8. Q8-induced dimerization of the ERalpha epitope augmented its
      affinity towards 14-3-3 through a binary bivalent binding mode. The crystal
      structure of the Q8-induced ternary complex revealed molecular insight into the
      multiple supramolecular interactions between the protein, the peptide, and Q8.

PMID- 28510305
TI  - Reactive Precipitation of Anhydrous Alkali Sulfide Nanocrystals with Concomitant
      Abatement of Hydrogen Sulfide and Cogeneration of Hydrogen.
AB  - Anhydrous alkali sulfide (M2 S, M=Li or Na) nanocrystals (NCs) are important
      materials central to the development of next generation cathodes and solid-state
      electrolytes for advanced batteries, but not commercially available at present.
      This work reports an innovative method to directly synthesize M2 S NCs through
      alcohol-mediated reactions between alkali metals and hydrogen sulfide (H2 S). In
      the first step, the alkali metal is complexed with alcohol in solution, forming
      metal alkoxide (ROM) and releasing hydrogen (H2 ). Next, H2 S is bubbled through
      the ROM solution, where both chemicals are completely consumed to produce phase
      pure M2 S NC precipitates and regenerate alcohol that can be recycled. The M2 S
      NCs morphology may be tuned through the choice of the alcohol and solvent. Both
      synthetic steps are thermodynamically favorable (DeltaGmo <-100 kJ mol-1 ),
      proceeding rapidly to completion at ambient temperature with almost 100 % atom
      efficiency. The net result, H2 S+2 m->M2 S+H2 , makes good use of a hazardous
      chemical (H2 S) and delivers two value-added products that naturally phase
      separate for easy recovery. This scalable approach provides an energy-efficient
      and environmentally benign solution to the production of nanostructured materials
      required in emerging battery technologies.

PMID- 28510307
TI  - Expansion and intensification of humoral autoimmune response in the transition
      from preclinical to full-blown primary biliary cholangitis.

PMID- 28510306
TI  - A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in
      Chinese population.
AB  - It has been proposed that the majority of disease-associated loci identified by
      genome-wide association studies (GWAS) are enriched in non-coding regions, such
      as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage
      case-control study to systematically evaluate the association of genetic variants
      in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in
      7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation
      stage: 1,065 cases and 1,290 controls). As a result, we identified that
      rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the
      increased risk of lung cancer (additive model in discovery stage: adjusted OR =
      1.31, 95%CI = 1.13-1.53, p = 3.846 * 10-4 in Nanjing GWAS; adjusted OR = 1.20,
      95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR =
      1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the
      association between rs12740674 and lung cancer risk reached 6.204 * 10-6
      (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome
      Atlas (TCGA) data and functional assays, we observed that the risk T allele of
      rs12740674 reduced the expression level of miR-1262 in lung tissue through
      chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell
      proliferation probably through targeting the expression levels of ULK1 and RAB3D.
      Our findings confirmed the important role that genetic variants of noncoding
      sequence play in lung cancer susceptibility and indicated that rs12740674 in miR
      1262 may be biologically relevant to lung carcinogenesis.

PMID- 28510308
TI  - Satisfaction is not substantially affected by quality of recovery: different
      constructs or are we lost in statistics?

PMID- 28510309
TI  - Molecular classification of hepatoblastoma and prognostic value of the HB 16-gene
      signature.

PMID- 28510310
TI  - Anal fistula height: is the proportion of sphincteric muscle involved really
      useful?

PMID- 28510311
TI  - Rapid Microfluidic Dilution for Single-Molecule Spectroscopy of Low-Affinity
      Biomolecular Complexes.
AB  - To enable the investigation of low-affinity biomolecular complexes with confocal
      single-molecule spectroscopy, we have developed a microfluidic device that allows
      a concentrated sample to be diluted by up to five orders of magnitude within
      milliseconds, at the physical limit dictated by diffusion. We demonstrate the
      capabilities of the device by studying the dissociation kinetics and structural
      properties of low-affinity protein complexes using single-molecule two-color and
      three-color Forster resonance energy transfer (FRET). We show that the
      versatility of the device makes it suitable for studying complexes with
      dissociation constants from low nanomolar up to 10 MUm, thus covering a wide
      range of biomolecular interactions. The design and precise fabrication of the
      devices ensure simple yet reliable operation and high reproducibility of the
      results.

PMID- 28510313
TI  - Categorization and theoretical comparison of quantitative methods for assessing
      QT/RR hysteresis.
AB  - BACKGROUND: In the human electrocardiogram, there is a lag of adaptation of the
      QT interval to heart rate changes, usually termed QT/RR hysteresis (QT-hys).
      Subject-specific quantifiers of QT-hys have been proposed as potential
      biomarkers, but there is no consensus on the choice of the quantifier. METHODS: A
      comprehensive literature search was conducted to identify original articles
      reporting quantifiers of repolarization hysteresis from the surface ECG in
      humans. RESULTS: Sixty articles fulfilled our inclusion criteria. Reported
      biomarkers were grouped under four categories. A simple mathematical model of
      QT/RR loop was used to illustrate differences between the methods. Category I
      quantifiers use direct measurement of QT time course of adaptation. They are
      limited to conditions where RR intervals are under strict control. Category IIa
      and IIb quantifiers compare QT responses during consecutive heart rate
      acceleration and deceleration. They are relevant when a QT/RR loop is observed,
      typically during exercise and recovery, but are not robust to protocol
      variations. Category III quantifiers evaluate the optimum RR memory in dynamic
      QT/RR relationship modeling. They estimate an intrinsic memory parameter
      independent from the nature of RR changes, but their reliability remains to be
      confirmed when multiple memory parameters are estimated. Promising approaches
      include the differentiation of short-term and long-term memory and adaptive
      estimation of memory parameters. CONCLUSION: Model-based approaches to QT-hys
      assessment appear to be the most versatile, as they allow separate quantification
      of QT/RR dependency and QT-hys, and can be applied to a wide range of
      experimental settings.

PMID- 28510312
TI  - The midbrain-to-pons ratio distinguishes progressive supranuclear palsy from non
      fluent primary progressive aphasias.
AB  - BACKGROUND AND PURPOSE: To determine the clinical utility of the midbrain-to-pons
      (M/P) ratio as a clinical biomarker of progressive supranuclear palsy (PSP) in
      patients with non-fluent primary progressive aphasia syndromes. METHODS: Patients
      with PSP, progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia
      (LPA) were recruited. Patients were diagnosed clinically, but pathological
      confirmation was available in a proportion of patients. Midbrain and pons areas
      were measured using Osirix Lite, a free DICOM viewer. The M/P ratio and Magnetic
      Resonance Parkinsonism Index were calculated and their diagnostic utility
      compared. RESULTS: A total of 72 participants were included (16 PSP, 18 PNFA, 16
      LPA and 22 controls). Patients with PSP had motor features typical of the
      syndrome. Both the M/P ratio and Magnetic Resonance Parkinsonism Index differed
      significantly in PSP compared with controls. The M/P ratio was disproportionately
      reduced in PSP compared with PNFA and LPA (PSP, 0.182 +/- 0.043; PNFA, 0.255 +/-
      0.034; LPA, 0.258 +/- 0.033; controls, 0.292 +/- 0.031; P < 0.001). An M/P ratio
      of <=0.215 produced a positive predictive value of 77.8% for the diagnosis of PSP
      syndrome. Pathological examination revealed Alzheimer's disease in three cases
      (all LPA), pathological PSP in two cases (one clinical PSP and one PNFA) and
      corticobasal degeneration in one case (PNFA). The M/P ratio was <=0.215 in both
      pathological cases of PSP. CONCLUSIONS: The M/P ratio was disproportionately
      reduced in PSP, suggesting its potential as a clinical marker of the PSP
      syndrome. Larger studies of pathologically confirmed cases are needed to
      establish the M/P ratio as a biomarker of PSP pathology.

PMID- 28510315
TI  - BK Virus Nephropathy Revisited.

PMID- 28510314
TI  - A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy.
AB  - The investigation of the mode and time course of the activation of G-protein
      coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M)
      receptors, is still in its infancy despite the tremendous therapeutic relevance
      of M receptors and GPCRs in general. We herein made use of a dualsteric ligand
      that can concomitantly interact with the orthosteric, that is, the
      neurotransmitter, binding site and an allosteric one. We synthetically
      incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized
      the photophysical properties of this ligand called BQCAAI and investigated its
      applicability as a pharmacological tool compound with a set of FRET techniques at
      the M1 receptor. BQCAAI proved to be an unprecedented molecular tool; it is the
      first photoswitchable dualsteric ligand, and its activity can be regulated by
      light. We also applied BQCCAI to investigate the time course of several receptor
      activation processes.

PMID- 28510316
TI  - Laparoscopic en bloc total mesorectal excision post chemoradiotherapy - a video
      vignette.

PMID- 28510317
TI  - Efflux Pumps Might Not Be the Major Drivers of QAC Resistance in Methicillin
      Resistant Staphylococcus aureus.
AB  - Quaternary ammonium compounds (QACs) are commonly used antiseptics that are now
      known to be subject to bacterial resistance. The prevalence and mechanisms of
      such resistance, however, remain underexplored. We investigated a variety of
      QACs, including those with multicationic structures (multiQACs), and the
      resistance displayed by a variety of Staphylococcus aureus strains with and
      without genes encoding efflux pumps, the purported main driver of bacterial
      resistance in MRSA. Through minimum inhibitory concentration (MIC)-, kinetic-,
      and efflux-based assays, we found that neither the qacR/qacA system present in S.
      aureus nor another efflux pump system is the main reason for bacterial resistance
      to QACs. Our findings suggest that membrane composition could be the predominant
      driver that allows CA-MRSA to withstand the assault of conventional QAC
      antiseptics.

PMID- 28510319
TI  - Response to Zinicola et al.

PMID- 28510318
TI  - Report From the American Society of Transplantation Conference on Donor Heart
      Selection in Adult Cardiac Transplantation in the United States.
AB  - Cardiac transplantation remains the only definitive treatment for end-stage heart
      failure. Transplantation rates are limited by a shortage of donor hearts. This
      shortage is magnified because many hearts are discarded because of strict
      selection criteria and concern for regulatory reprimand for less-than-optimal
      posttransplant outcomes. There is no standardized approach to donor selection
      despite proposals to liberalize acceptance criteria. A donor heart selection
      conference was organized to facilitate discussion and generate ideas for future
      research. The event was attended by 66 participants from 41 centers with
      considerable experience in cardiac donor selection. There were state-of-the-art
      presentations on donor selection, with subsequent breakout sessions on
      standardizing the process and increasing utilization of donor hearts.
      Participants debated misconceptions and established agreement on donor and
      recipient risk factors for donor selection and identified the components
      necessary for a future donor risk score. Ideas for future initiatives include
      modification of regulatory practices to consider extended criteria donors when
      evaluating outcomes and prospective studies aimed at identifying the factors
      leading to nonacceptance of available donor hearts. With agreement on the most
      important donor and recipient risk factors, it is anticipated that a consistent
      approach to donor selection will improve rates of heart transplantation.

PMID- 28510320
TI  - Selective Si-C(sp3 ) Bond Cleavage in (Aminomethyl)silanes by Carbanionic
      Nucleophiles and Its Stereochemical Course.
AB  - Selective cleavage of a silicon-carbon bond in tetraorganosilanes is still a
      great challenge. A new type of Si-C(sp3 ) bond cleavage in bench-stable
      (aminomethyl)silanes with common organolithium reagents as nucleophiles has now
      been identified. Suitable leaving groups are benzyl, allyl, and phenylthiomethyl
      groups. A beta-donor function and polar solvents are essential for the reaction.
      Simple switching between alpha-deprotonation and substitution is possible through
      slight modifications of the reaction conditions. The stereochemical course of the
      reaction was elucidated by using a silicon-chiral benzylsilane. The new
      transformation proceeds stereospecifically with inversion of configuration and
      can be used for the targeted synthesis of enantiomerically pure
      tetraorganosilanes, which are otherwise difficult to access. Quantum chemical
      calculations provided insight into the mechanism of the new substitution.

PMID- 28510321
TI  - Novel ZnS/Carbon Nanofiber Photocatalyst for Degradation of Rhodamine 6G:
      Kinetics Tracking of Operational Parameters and Development of a Kinetics Model.
AB  - A novel nanocomposite in the role of photocatalyst was prepared by composition of
      zinc sulfide (ZnS) nanoparticles with carbon nanofibers (CNFs) and was
      characterized. The XRD, EDX, and FE-SEM analysis revealed that ZnS is
      successfully embedded in CNFs matrix. The DRS results indicated that supporting
      of ZnS by CNFs led to a decrease of the band gap energy. The photocatalytic
      degradation of a hazardous xanthine dye, Rhodamine 6 G (Rh-6G), by the prepared
      ZnS/CNFs composite was examined from the kinetics point of view. Nonlinear
      regression analysis was used to develop a mathematical kinetics model based on
      the Langmuir-Hinshelwood mechanism, and an empirical equation was obtained for
      the estimation of apparent pseudo-first-order rate constant (kap ) as a function
      of operational parameters (viz. initial dye concentration, ZnS/CNFs content, pH,
      and irradiation intensity). Based on the results, kap increased with an increase
      ZnS/CNFs content, pH, and UV light intensity, whereas it decreased by increasing
      the initial Rh-6G concentration. Moreover, a new kinetics model was obtained
      based on proposed elementary steps to determine kap . In the final stage of the
      work, intermediate materials produced within photocatalytic degradation of Rh-6G
      dye were detected by GC-MS analysis.

PMID- 28510322
TI  - Does Medical Students Knowing More About Drugs Lead to Better Treatment Choices?

PMID- 28510324
TI  - Mutual Gaze During Early Mother-Infant Interactions Promotes Attention Control
      Development.
AB  - Efficient attention control is fundamental for infant cognitive development, but
      its early precursors are not well understood. This study investigated whether
      dyadic visual attention during parent-infant interactions at 5 months of age
      predicts the ability to control attention at 11 months of age (N = 55). Total
      duration of mutual gaze (MG) was assessed during free play at 5 months, while
      infant attention control was measured in a gap-and-overlap task at 5 and 11
      months. MG predicted attention disengagement at 11 months. Infants who spent more
      time in MG at 5 months showed better attention control at 11 months. These
      results provide important insights into developmental pathways linking visual
      behavior in dyadic interactions with infants' subsequent attention skills.

PMID- 28510323
TI  - A Systematic Review and Pooled Analysis of Select Safety Parameters Among Normal
      Healthy Volunteers Taking Placebo in Phase 1 Clinical Trials.
AB  - A systematic review of the Bristol-Myers Squibb normal healthy volunteers (NHVs)
      database identified phase 1 trials that included NHVs administered placebo with
      the aim of characterizing normal inter- and intraindividual safety parameter
      variability. Twenty-five single and multiple ascending dose studies, median
      duration 28 (2 to 63) days, were included in the pooled analysis (355 NHVs).
      Laboratory evaluations, vital signs, electrocardiograms, and adverse events were
      assessed. The most commonly occurring adverse event was headache (28 [7.9%] NHVs;
      519.5 events/100 person-years). During the dosing period (on placebo),
      evaluations showed 5.1 events/100 measures of alanine aminotransferase and 7.3
      events/100 measures of creatine kinase 1* above the upper limit of normal.
      Alanine aminotransferase and creatine kinase elevations occurred in 28 (7.9%) and
      39 (11.0%) NHVs, respectively; 105 (30.3%) NHVs had low and 46 (13.3%) had high
      diastolic blood pressure. This analysis may inform future study designs and
      provide a context for interpretation of safety signals in early phase clinical
      trials.

PMID- 28510325
TI  - Structural Dynamics upon Photoexcitation in a Spin Crossover Crystal Probed with
      Femtosecond Electron Diffraction.
AB  - Photoexcitation of spin crossover (SCO) complexes can trigger extensive
      electronic spin transitions and transformation of molecular structure. However,
      the precise nature of the associated ultrafast structural dynamics remains
      elusive, especially in the solid state. Here, we studied a single-crystal SCO
      material with femtosecond electron diffraction (FED). The unique capability of
      FED allows us to directly probe atomic motions and to track ultrafast structural
      changes within a crystal lattice. By monitoring the time-dependent changes of the
      Bragg reflections, we observed the formation of a photoinduced structure similar
      to the thermally induced high-spin state. The data and refinement calculations
      indicate the global structural reorganization within 2.3 ps, as the metal-ligand
      bond distribution narrows during intramolecular vibrational energy redistribution
      (IVR) driving the intermolecular rearrangement. Three independent dynamical group
      are identified to model the structural dynamics upon photoinduced SCO.

PMID- 28510326
TI  - Total Synthesis of Homodimericin A.
AB  - We report the concise total synthesis of homodimericin A (1), a recently
      identified fungal metabolite bearing an unprecedented molecular architecture. The
      success of the approach hinges on a series of rationally designed and bioinspired
      transformations, including a Moore rearrangement to assemble the monomeric
      hydroquinone precursor, homodimerization through double Michael addition to
      construct the planar A/B/C tricyclic framework, and a tandem Diels-Alder
      reaction/carbonyl-ene cyclization to forge the congested D/E/F tricyclic cage
      motif. Unequivocal evidence for the elucidated structure of homodimericin A was
      also provided by this study.

PMID- 28510327
TI  - Pre-existing diabetes is a risk factor for increased rates of cellular rejection
      after kidney transplantation: an observational cohort study.
AB  - AIM: To investigate whether people with diabetes have an elevated risk of kidney
      allograft rejection in a well characterized clinical cohort in the setting of
      contemporary immunosuppression. METHODS: We conducted a retrospective cohort
      study including all kidney allograft recipients at a single centre between 2007
      and 2015, linking clinical, biochemical and histopathological data from
      electronic patient records. RESULTS: Data were analysed for 1140 kidney
      transplant recipients. The median follow-up was 4.4 years post-transplantation,
      and 117 of the kidney transplant recipients (10.2%) had diabetes at time of
      transplantation. Kidney allograft recipients with vs without diabetes were older
      (53 vs 45 years; P<0.001) and more likely to be non-white (41.0% vs 26.4%;
      P=0.001). Kidney allograft recipients with vs without diabetes had a higher risk
      of cellular rejection (19.7% vs 12.4%; P=0.024), but not of antibody-mediated
      rejection (3.4% vs 3.7%; P=0.564). Graft function and risk of death-censored
      graft loss were similar in the two groups, but kidney allograft recipients with
      diabetes had a higher risk of death and overall graft loss than those without
      diabetes. In a Cox regression model of non-modifiable risk factors at time of
      transplantation, diabetes was found to be an independent risk factor for cellular
      rejection (hazard ratio 1.445, 95% CI 1.023-1.945; P=0.042). CONCLUSIONS: Kidney
      allograft recipients with diabetes at transplantation should be counselled
      regarding their increased risk of cellular rejection but reassured regarding the
      lack of any adverse impact on short-to-medium term allograft function or
      survival.

PMID- 28510329
TI  - Isolation of Stem Cells and Progenitors from Mouse Epidermis.
AB  - The epidermis consists of several distinct compartments including the
      interfollicular epidermis (IFE), sweat glands, sebaceous glands (SGs), and the
      hair follicle (HF). While the IFE and SGs are in a constant state of self
      renewal, the HF cycles between phases of growth, destruction, and rest. The hair
      follicle stem cells (HFSCs) that fuel this perpetual cycle have been well
      described and are located in a niche termed the bulge. These bulge SCs express
      markers such as CD34 and Keratin 15 (K15), enabling the isolation of these cells.
      Here, we describe a powerful method for isolating HFSCs and epidermal progenitors
      from mouse skin utilizing fluorescence activated cell-sorting (FACS). Upon
      isolation, cells can be expanded and utilized in various in vivo and in vitro
      models aimed at studying the function of these unique cells. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 28510330
TI  - Rhesus Macaque iPSC Generation and Maintenance.
AB  - The rhesus macaque (Macaca mulatta) is physiologically and phylogenetically
      similar to humans, and therefore represents an invaluable model for the pre
      clinical assessment of the safety and feasibility of iPSC-derived cell therapies.
      The use of an excisable polycistronic lentiviral STEMCCA vector to reprogram
      rhesus fibroblasts or bone marrow stromal cells (BMSCs) into RhiPSCs is
      described. After reprogramming, the pluripotency transgenes can be removed by
      transient expression of Cre, leaving a residual genetic tag that may be useful
      for identification of RhiPSC-derived tissues in vivo. Finally, the steps to
      maintain pluripotency during passaging of RhiPSCs, required for successful
      utilization of RhiPSCs, is described. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28510331
TI  - Isolation of Ready-to-Use Adipose-Derived Stem Cell (ASC) Pellet for Clinical
      Applications and a Comparative Overview of Alternate Methods for ASC Isolation.
AB  - Current literature does not offer a standardized method to isolate adipose
      derived stem cells (ASCs) for clinical applications and hence clinical studies
      using ASCs often show inconsistent results. Most of these studies borrow
      laboratory or benchside-derived protocols, which are complex, time consuming, and
      involve the use of chemical, animal-derived reagents. In this unit we describe a
      relatively simple and faster isolation protocol that allows collection of a ready
      to-use ASC pellet for clinical application. All steps are performed in a closed
      circuit in order to guarantee maximum process sterility. Once the adipose tissue
      is harvested by means of a standard liposuction procedure, it undergoes a first
      centrifugation in order to remove the oil and serous fractions. Then ASCs are
      released by enzymatic digestion from the surrounding connective tissue scaffold.
      Finally a double series of washing and centrifugation allows one to obtain the
      ASC pellet alone. We usually graft this ASC pellet onto the skin edge and to the
      bottom of chronic skin ulcers as ASCs proved to be effective in promoting wound
      healing processes. Moreover, an increasing number of clinical studies are
      currently ongoing to test their potential in every medical field, from
      orthopedics to cardiology, oncology, autoimmune diseases, and tissue engineering.
      (c) 2017 by John Wiley & Sons, Inc.

PMID- 28510328
TI  - Genetic variants in the genes encoding rho GTPases and related regulators predict
      cutaneous melanoma-specific survival.
AB  - Rho GTPases control cell division, motility, adhesion, vesicular trafficking and
      phagocytosis, which may affect progression and/or prognosis of cancers. Here, we
      investigated associations between genetic variants of Rho GTPases-related genes
      and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published
      melanoma genome-wide association study (GWAS) and validating the results in
      another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho
      related genes, 427 SNPs were significantly associated with CMSS (p < 0.050 and
      false-positive report probability <0.2) in the discovery dataset, and five SNPs
      were replicated in the validation dataset. Among these, four SNPs (i.e., RHOU
      rs10916352 G > C, ARHGAP22 rs3851552 T > C, ARHGAP44 rs72635537 C > T and
      ARHGEF10 rs7826362 A > T) were independently predictive of CMSS (a meta-analysis
      derived p = 9.04 * 10-4 , 9.58 * 10-4 , 1.21 * 10-4 and 8.47 * 10-4 ,
      respectively). Additionally, patients with an increasing number of unfavorable
      genotypes (NUGs) of these loci had markedly reduced CMSS in both discovery
      dataset and validation dataset (ptrend =1.47 * 10-7 and 3.12 * 10-5 ). The model
      including the NUGs and clinical variables demonstrated a significant improvement
      in predicting the five-year CMSS. Moreover, rs10916352C and rs3851552C alleles
      were significantly associated with an increased mRNA expression levels of RHOU (p
      = 1.8 * 10-6 ) and ARHGAP22 (p = 5.0 * 10-6 ), respectively. These results may
      provide promising prognostic biomarkers for CM personalized management and
      treatment.

PMID- 28510332
TI  - Human Umbilical Cord Mesenchymal Stromal Cell Isolation, Expansion,
      Cryopreservation, and Characterization.
AB  - Revised methods to derive, expand, and characterize mesenchymal stromal cells
      (MSCs) from the umbilical cord are provided. Several considerations are taken for
      GMP compliance including using a closed system isolation method and eliminating
      several xenogenic components. With this method cells are isolated using
      mechanical and enzymatic digestion and then expanded with high viabilities that
      retain >90% viability after cryopreservation. Lastly, characterization methods
      have been optimized to identify these cells as MSCs according to the ISCT minimal
      criteria. This method standardizes the process for isolating, expanding,
      cryopreserving, and characterizing MSCs from the umbilical cord. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 28510334
TI  - Angiogenesis within Stem Cell-Seeded Silk Scaffolds Cultured on the
      Chorioallantoic Membrane and Visualized by 3D Imaging.
AB  - The long-term survival and successful integration of implants for tissue
      replacement and regeneration highly depends upon the fast ingrowth of blood
      vessels from the surrounding tissues. Before selecting potential biomaterials for
      clinical applications, they must be thoroughly tested with proper analytical
      tools. This unit provides a protocol for studying the potential of cell-seeded
      scaffolds to attract vessels that will form vascular networks within
      biomaterials. It includes seeding of stem cells into silk fibroin scaffolds,
      angiogenesis assay on the chorioallantoic membrane (CAM) of fertilized chicken
      eggs, a procedure for perfusion with MicroFil, and finally microcomputed
      tomography (uCT) scanning. This technique can help screen potential biomaterial
      implants, thereby reducing the amount of animals needed for pre-clinical in vivo
      studies. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28510333
TI  - Tetracycline-Inducible and Reversible Stable Gene Expression in Human iPSC
      Derived Neural Progenitors and in the Postnatal Mouse Brain.
AB  - The pB-tet-GOI plasmid system allows for stable piggyBac transposition-mediated
      integration into cells, a fluorescent nuclear reporter to identify cells that
      have been transfected, and robust transgene activation or suppression upon the
      addition of dox to the cell culture or diet of the animal. Furthermore, the
      addition of luciferase downstream of the target gene allows for quantitative
      assessment of gene activity in a non-invasive manner. The protocols herein
      provide instructions for the use of this system in cell lines and in the neonatal
      mouse brain. Specifically, a detailed protocol is provided to illustrate: (1)
      cloning of the respective GOI (genetic element(s) of interest); (2) nucleofection
      of the plasmid system into human induced pluripotent stem cell (iPSC)-derived
      neural progenitors; (3) dox-induced activation in vitro or in vivo; and (4) non
      invasive assessment of gene activity in vivo by bioluminescence imaging. (c) 2017
      by John Wiley & Sons, Inc.

PMID- 28510337
TI  - Highly Rechargeable Lithium-CO2 Batteries with a Boron- and Nitrogen-Codoped
      Holey-Graphene Cathode.
AB  - Metal-air batteries, especially Li-air batteries, have attracted significant
      research attention in the past decade. However, the electrochemical reactions
      between CO2 (0.04 % in ambient air) with Li anode may lead to the irreversible
      formation of insulating Li2 CO3 , making the battery less rechargeable. To make
      the Li-CO2 batteries usable under ambient conditions, it is critical to develop
      highly efficient catalysts for the CO2 reduction and evolution reactions and
      investigate the electrochemical behavior of Li-CO2 batteries. Here, we
      demonstrate a rechargeable Li-CO2 battery with a high reversibility by using B,N
      codoped holey graphene as a highly efficient catalyst for CO2 reduction and
      evolution reactions. Benefiting from the unique porous holey nanostructure and
      high catalytic activity of the cathode, the as-prepared Li-CO2 batteries exhibit
      high reversibility, low polarization, excellent rate performance, and superior
      long-term cycling stability over 200 cycles at a high current density of 1.0 A g
      1 . Our results open up new possibilities for the development of long-term Li-air
      batteries reusable under ambient conditions, and the utilization and storage of
      CO2 .

PMID- 28510335
TI  - Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers
      in Liver Transplant Recipients.
AB  - Biomarker profiles of acute rejection in liver transplant recipients could
      enhance the diagnosis and management of recipients. Our aim was to identify
      diagnostic proteoform signatures of acute rejection in circulating immune cells,
      using an emergent "top-down" proteomics methodology. We prepared differentially
      processed and cryopreserved cell lysates from 26 nonviral liver transplant
      recipients by molecular weight-based fractionation and analyzed them by mass
      spectrometry of whole proteins in three steps: (i) Nanocapillary liquid
      chromatography coupled with high-resolution tandem mass spectrometry; (ii)
      database searching to identify and characterize intact proteoforms; (iii) data
      processing through a hierarchical linear model matching the study design to
      quantify proteoform fold changes in patients with rejection versus normal liver
      function versus acute dysfunction without rejection. Differentially expressed
      proteoforms were seen in patients with rejection versus normal and nonspecific
      controls, most evidently in the cell preparations stored in traditional serum
      rich media. Mapping analysis of these proteins back to genes through gene
      ontology and pathway analysis tools revealed multiple signaling pathways,
      including inflammation mediated by cytokines and chemokines. Larger studies are
      needed to validate these novel rejection signatures and test their predictive
      value for use in clinical management.

PMID- 28510336
TI  - Epistaxis in anticoagulated patients: Fewer hospital admissions and shorter
      hospital stays on rivaroxaban compared to phenprocoumon.
AB  - OBJECTIVES: Treatment of epistaxis in patients on anticoagulants is challenging
      and associated with higher admission rates and longer hospital stays compared
      with patients without anticoagulation. However, there is little information about
      epistaxis in patients taking new direct oral anticoagulants such as rivaroxaban
      compared with patients on traditional vitamin K antagonists such as
      phenprocoumon. DESIGN: Retrospective cohort study. SETTING: The study was
      conducted at the emergency department of the University Hospital Inselspital,
      Bern, Switzerland. PARTICIPANTS: All admissions to the emergency department of
      the University Hospital Inselspital, Bern, Switzerland from 1st July 2012 to 30th
      June 2016 with non-traumatic epistaxis on anticoagulant therapy with
      phenprocoumon or rivaroxaban were included. MAIN OUTCOME MEASURES: We compared
      clinical outcome parameters (admission rates, length of hospital stay and
      mortality) for both anticoagulant groups. RESULTS: We included 440 patients with
      epistaxis, 123 (28%) on rivaroxaban and 317 (72%) on phenprocoumon. Fewer
      hospital admissions and shorter hospital stays were found in patients under
      rivaroxaban (12 (10.4%) vs 57 (18.0%) patients, P=.033; 0.7+/-2.2 vs 1.5+/-3.7
      days, P=.011) compared with phenprocoumon. Anterior epistaxis was more common in
      the rivaroxaban group in contrast to posterior epistaxis in patients on
      phenprocoumon (74 (60.2%) vs 139 (43.8%) patients, P=.002; 7 (5.7%) vs 39 (12.3%)
      patients, P=.042). CONCLUSIONS: Our data suggests that epistaxis on direct oral
      anticoagulation with rivaroxaban is associated with shorter hospital stays and
      fewer hospital admissions than epistaxis on vitamin K antagonist phenprocoumon.

PMID- 28510338
TI  - Therapeutic Targeting of Poly(ADP-Ribose) Polymerase-1 (PARP1) in Cancer: Current
      Developments, Therapeutic Strategies, and Future Opportunities.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) plays a central role in numerous cellular
      processes including DNA repair, replication, and transcription. PARP interacts
      directly, indirectly or via PARylation with various oncogenic proteins and
      regulates several transcription factors thereby modulating carcinogenesis.
      Therapeutic inhibition of PARP is therefore perceived as a promising anticancer
      strategy and a number of PARP inhibitors (PARPi) are currently under development
      and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the
      concept of synthetic lethality in cancer therapeutics. Preclinical and clinical
      studies have shown the potential of PARPi as chemopotentiator, radiosensitizer,
      or as adjuvant therapeutic agents. Recent studies have shown that PARP-1 could be
      either oncogenic or tumor suppressive in different cancers. PARP inhibitor
      resistance is also a growing concern in the clinical setting. Recently, changes
      in the levels of PARP-1 activity or expression in cancer patients have provided
      the basis for consideration of PARP-1 regulatory proteins as potential
      biomarkers. This review focuses on the current developments related to the role
      of PARP in cancer progression, therapeutic strategies targeting PARP-associated
      oncogenic signaling, and future opportunities in use of PARPi in anticancer
      therapeutics.

PMID- 28510339
TI  - Pharmacokinetics of Tedizolid in Obese and Nonobese Subjects.

PMID- 28510340
TI  - Immortal time bias or sorafenib effect in elderly patients with HCC?

PMID- 28510341
TI  - Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single
      Center Experience.
AB  - Over the past two decades, the age of liver transplantation (LT) recipients has
      been increasing. We reviewed our experience with LT for patients aged >=70 years
      (range: 70-78 years) and investigated the feasibility of performing LT,
      especially living donor LT (LDLT), for older patients. We retrospectively
      reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased
      donor LT recipients) aged >=70 years who underwent LT from January 2000 to April
      2016. Their perioperative morbidity rate was 28.0%, and the in-hospital mortality
      rate was 16.0%; these results were comparable to those of matched patients in
      their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in
      their 70s, the 1- and 5-year patient survival rates were 84.0% and 69.8%, and the
      1- and 5-year graft survival rates were 83.5% and 75.1%, respectively.
      Comparisons of patient and graft survival rates between matched patients in their
      60s and 70s showed no statistically significant differences (patient survival, p
      = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged
      >=70 years should not be excluded from LT, or even LDLT, based solely on age and
      implies that careful selection of recipients and donors as well as meticulous
      surgical technique are necessary for successful results.

PMID- 28510342
TI  - Constructing a Robust Fluorescent DNA-Stabilized Silver Nanocluster Probe Module
      by Attaching a Duplex Moiety.
AB  - Fluorescent DNA-templated silver nanoclusters (DNA-Ag NCs) have served as
      excellent luminescent probes and operation units in various applications.
      However, the fluorescence property of DNA-Ag NCs is very sensitive to elongation
      or modification of the DNA template, limiting the breadth of applications. In
      this work, we propose a strategy for constructing a robust fluorescent DNA-Ag NCs
      probe module by attaching a duplex moiety to the nanocluster-bearing sequence.
      The fluorescence intensity of the DNA-Ag NCs can be enhanced 90-fold upon
      hybridization of the elongated moiety. Adenine in the linker sequence has a
      further enhancing effect on the fluorescence intensity, whereas thymine has a
      quenching effect. The transformation from a non-fluorescent species to
      fluorescent nanoclusters is responsible for the fluorescence enhancement with
      duplex formation of the elongated moiety. We hope that this design will aid
      future diversification of experimental designs to facilitate more applications
      that are currently limited by the aforementioned problems.

PMID- 28510344
TI  - Harnessing [1,4], [1,5], and [1,6] Anionic Fries-type Rearrangements by Reaction
      Time Control in Flow.
AB  - A series of anionic Fries-type rearrangements of carbamoyl-substituted
      aryllithium intermediates were controlled by using flow microreactor systems. For
      the [1,4] and [1,5] rearrangements, the aryllithium intermediate formed before
      carbamoyl migration and the lithium alkoxide formed after carbamoyl migration can
      be selectively subjected to subsequent reactions with electrophiles by precisely
      controlling the residence time and temperature (-25 to -50  degrees C). In
      contrast, the [1,6] rearrangement is rather slow even at -25  degrees C. The
      absence of crossover products indicates the intramolecular nature of the
      carbamoyl group migration.

PMID- 28510343
TI  - No effect of HLA-C mismatch after allogeneic hematopoietic stem cell
      transplantation with unrelated donors and T-cell depletion in patients with
      hematological malignancies.
AB  - HLA-C mismatch in unrelated donor's hematopoietic stem cell transplantation
      (HSCT) has been associated with poor patient outcome. However, the impact of HLA
      C mismatch in the context of HSCT combined with in vivo T-cell depletion remains
      unclear. We therefore performed a single-center, retrospective analysis of the
      clinical outcome on patients with hematological malignancies treated with allo
      HSCT, who underwent T-cell depletion. The majority of the patients (n=276)
      received a HLA-A, HLA-B, HLA-DRB1-matched graft that were either also HLA-C
      matched (n=260), or patients with the permissive HLA-C*03:03/03:04 mismatch
      (n=16), while the remaining patients (n=95) received a HLA-C-mismatched graft
      (excluding HLA-C*03:03/03:04 mismatches). We did not observe any significant
      differences between the HLA-C-matched patients (including the permissive HLA
      C*03:03/03:04 mismatch) and the HLA-C-mismatched patients regarding cumulative
      proportion surviving, graft failure, relapse-free survival, relapse, or acute
      graft-versus-host disease. Our data suggest that in the context of high dose T
      lymphocyte-depleting agents, HLA-C matching is not essential for patients with
      hematological malignancies.

PMID- 28510345
TI  - Mandarin parents' evaluation of developmental status in the detection of delays.
AB  - BACKGROUND: We examined the parental perception and accuracy of the Mandarin
      translation of the Parents' Evaluation of Developmental Status, a screening
      questionnaire for parent concerns about children's various developmental skills.
      METHODS: The questionnaire was translated into Mandarin. Upon enrollment,
      caregivers completed the Mandarin PEDS and answered four questions about its
      acceptability and usefulness, and its ease of understanding and completion. The
      Mandarin PEDS was independently evaluated by a pediatrician and a community
      nurse, and classified as high risk (>=two predictive concerns), medium risk (one
      predictive concern), low risk (any non-predictive concerns) or no risk (if no
      concern) for developmental delays. The caregivers repeated Mandarin PEDS at a 2
      week interval for test-retest reliability, while the children underwent testing
      for accuracy using a developmental assessment test. RESULTS: The majority (>=85%)
      of the 73 caregivers perceived the Mandarin PEDS as acceptable and useful, as
      well as easy to understand and complete. Fifteen (20.5%) and 24 responses (33.9%)
      were classified as high and moderate risk, respectively. The test-retest and
      inter-rater reliabilities were excellent, with an intra-class correlation
      coefficient of 0.812 (95% CI: 0.701-0.881, P < 0.001) and a kappa value of 0.870
      (P < 0.001), respectively. Mandarin PEDS was 80.0% sensitive and 83.8% specific
      for those in the high-risk category (adjusted OR, 64.68; 95% CI: 1.33-3,139.72; P
      = 0.035). CONCLUSION: Mandarin PEDS was well received by the caregivers, and was
      reliable and accurate in detecting developmental delays in the Mandarin-speaking
      subjects. We recommend it for early detection of children with developmental and
      behavioral problems.

PMID- 28510346
TI  - Lack of Effect of Rivipansel on QTc Interval in Healthy Adult African American
      Male Subjects.
AB  - Rivipansel is a pan-selectin inhibitor in phase 3 development for the treatment
      of vaso-occlusive crises in patients with sickle cell disease. This single-dose,
      randomized, 3-period, 3-treatment (400 mg moxifloxacin open-label, 4 g rivipansel
      blinded, and placebo-blinded) crossover study evaluated the effect of rivipansel
      on the QT/QTc interval in 48 healthy male African American subjects (age, 21-53
      years; weight, 60-115 kg). Time-matched, placebo-adjusted change from baseline QT
      interval using Fridericia's correction method (QTcF) was determined using a
      repeated-measures mixed-effects model. The highest upper bound of the 2-sided 90%
      confidence interval (CI) for QTcF change was 3.22 milliseconds 3 hours postdose.
      Moxifloxacin showed the anticipated QTcF effect, indicating that the study had
      adequate sensitivity to detect changes in the QTcF interval. The study concluded
      that no QTcF effect was demonstrated with rivipansel compared with placebo, as
      the upper bound of the 2-sided 90%CI was less than 10 milliseconds at all times.
      Exposure-response modeling for rivipansel concentrations and change from baseline
      in QTcF data corroborated a lack of effect with rivipansel compared with placebo.
      Single doses of rivipansel 4 g by intravenous infusion over 20 minutes were well
      tolerated in this study.

PMID- 28510348
TI  - Regioselective Synthesis of Polycyclic and Heptagon-embedded Aromatic Compounds
      through a Versatile pi-Extension of Aryl Halides.
AB  - A versatile pi-extension reaction was developed based on the three-component
      cross-coupling of aryl halides, 2-haloarylcarboxylic acids, and norbornadiene.
      The transformation is driven by the direction and subsequent decarboxylation of
      the carboxyl group, while norbornadiene serves as an ortho-C-H activator and
      ethylene synthon via a retro-Diels-Alder reaction. Comprehensive DFT calculations
      were performed to account for the catalytic intermediates.

PMID- 28510347
TI  - Bioluminescent Antibodies for Point-of-Care Diagnostics.
AB  - We introduce a general method to transform antibodies into ratiometric,
      bioluminescent sensor proteins for the no-wash quantification of analytes. Our
      approach is based on the genetic fusion of antibody fragments to NanoLuc
      luciferase and SNAP-tag, the latter being labeled with a synthetic fluorescent
      competitor of the antigen. Binding of the antigen, here synthetic drugs, by the
      sensor displaces the tethered fluorescent competitor from the antibody and
      disrupts bioluminescent resonance energy transfer (BRET) between the luciferase
      and fluorophore. The semisynthetic sensors display a tunable response range
      (submicromolar to submillimolar) and large dynamic range (DeltaRmax >500 %), and
      they permit the quantification of analytes through spotting of the samples onto
      paper followed by analysis with a digital camera.

PMID- 28510349
TI  - Potential Disadvantages of Overcentralization of Organ Recovery Centers: Response
      to Marsolais et al.

PMID- 28510352
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 22/2017.

PMID- 28510350
TI  - Real-life comparison of three general paediatric wards showed similar outcomes
      for children with bronchiolitis despite different treatment regimens.
AB  - AIM: This study evaluated the effectiveness of three different treatments for
      bronchiolitis in a tertiary paediatric facility. METHODS: Patients with
      bronchiolitis who were younger than two years of age and were randomly allocated
      to three general wards at Schneider Children's Medical Center, Israel, after
      admission were included. Different treatment protocols in the wards were
      retrospectively compared. RESULTS: The study comprised 286 children. The clinical
      and laboratory parameters on admission were similar between the wards. In Ward C
      where nebulised hypertonic saline was infrequently administered (6.7%), the mean
      number of days with oxygen saturation under 92% and the meanlength of hospital
      stay (1.8 and 3.8 days) were significantly lower than Ward A (2.8 and 5.3 days)
      and Ward B, (2.9 and 4.7 days) where nebulised hypertonic saline was given more
      frequently (38.7%-74.7%). Multivariate analysis indicated that low saturation on
      admission, leukocytosis and use of nebulised hypertonic saline or adrenalin were
      independent predictors of a longer period of desaturation and hospital stay.
      CONCLUSION: Different treatment protocols for bronchiolitis were used in three
      paediatric wards in this real-life study. No treatment regimen proved superior.
      Inhalations of hypertonic saline or adrenaline were associated with a longer
      hospital stay.

PMID- 28510351
TI  - Using N-Heterocyclic Vinyl Ligands to Access Stable Divinylgermylenes and a
      Germylium Cation.
AB  - Two efficient methods are presented to install sigma- and pi-electron-donating N
      heterocyclic vinyl groups onto main-group elements (E): halosilane elimination
      and base-induced E-C bond formation. Placement of two NHC=CH- ligands (NHC=N
      heterocyclic carbene) onto a GeII center affords a two-coordinate germylene, a
      heavy congener of the elusive divinyl carbenes. The pi-donating ability of this
      vinylic ligand scaffold was further demonstrated by the synthesis of a three
      coordinate germylium cation R3 Ge+ .

PMID- 28510353
TI  - Crystal-Packing-Driven Enrichment of Atropoisomers.
AB  - Crystal-packing forces can have a significant impact on the relative stabilities
      of different molecules and their conformations. The magnitude of such effects is,
      however, not yet well understood. Herein we show, that crystal packing can
      completely overrule the relative stabilities of different stereoisomers in
      solution. Heating of atropoisomers (i.e. "frozen-out" conformational isomers) in
      solution leads to complex mixtures. In contrast, solid-state heating selectively
      amplifies minor (<25 mole %) components of these solution-phase mixtures. We show
      that this heating strategy is successful for compounds with up to four
      rotationally hindered sigma bonds, for which a single stereoisomer out of seven
      can be amplified selectively. Our results demonstrate that common supramolecular
      interactions-for example, [methyl???pi] coordination and [C-H???O] hydrogen
      bonding-can readily invert the relative thermodynamic stabilities of different
      molecular conformations. These findings open up potential new avenues to control
      the folding of macromolecules.

PMID- 28510354
TI  - That's what friends are for: how intergroup friendships promote historically
      disadvantaged groups' substantive political representation.
AB  - The interests of historically disadvantaged groups risk being overlooked if they
      are not present in the decision-making process. However, a mere presence in
      politics does not guarantee political success. Often groups need allies to
      promote their interests successfully. We argue that one way to identify such
      allies is to judge politicians by whether they have friends in historically
      disadvantaged groups, as intergroup friendships have been shown to make people
      understand and feel empathy for outgroups. In other words, intergroup friendships
      may function as an important complement to descriptive representation. We test
      our argument with a unique survey that asks all elected political representatives
      in Sweden's 290 municipalities (response rate 79 per cent) about their friendship
      ties to, and their representation of, five historically disadvantaged groups:
      women, immigrants, youths, pensioners and blue-collar workers. We find a strong
      correlation between representatives' friendship ties to these groups and their
      commitment to represent them. The correlation is especially strong for youths and
      blue-collar workers, which likely can be explained by the fact that these groups
      usually lack crucial political resources (such as experience and education). We
      conclude that friendship ties function as an important complement to descriptive
      representation for achieving substantive representation.

PMID- 28510356
TI  - Purification of recombinant Abeta(1-42) and pGlu-Abeta(3-42) using preparative
      SDS-PAGE.
AB  - Recombinant expression and purification of amyloid peptides represents a common
      basis for investigating the molecular mechanisms of amyloid formation and
      toxicity. However, the isolation of the recombinant peptides is hampered by
      inefficient separation from contaminants such as the fusion protein required for
      efficient expression in E. coli. Here, we present a new approach for the
      isolation of highly purified Abeta(1-42) and pGlu-Abeta(3-42), which is based on
      a separation using preparative SDS-PAGE. The method relies on the purification of
      the Abeta fusion protein by affinity chromatography followed by preparative SDS
      PAGE under reducing conditions and subsequent removal of detergents by
      precipitation. The application of preparative SDS-PAGE represents the key step to
      isolate highly pure recombinant Abeta, which has been applied for
      characterization of aggregation and toxicity. Thereby, the yield of the
      purification strategy was  >60%. To the best of our knowledge, this is the first
      description of an electrophoresis-based method for purification of a recombinant
      Abeta peptide. Therefore, the method might be of interest for isolation of other
      amyloid peptides, which are critical for conventional purification strategies due
      to their aggregation propensity.

PMID- 28510355
TI  - The National Landscape of Living Kidney Donor Follow-Up in the United States.
AB  - In 2013, the Organ Procurement and Transplantation Network (OPTN)/ United Network
      for Organ Sharing (UNOS) mandated that transplant centers collect data on living
      kidney donors (LKDs) at 6 months, 1 year, and 2 years postdonation, with policy
      defined thresholds for the proportion of complete living donor follow-up (LDF)
      data submitted in a timely manner (60 days before or after the expected visit
      date). While mandated, it was unclear how centers across the country would
      perform in meeting thresholds, given potential donor and center-level challenges
      of LDF. To better understand the impact of this policy, we studied Scientific
      Registry of Transplant Recipients data for 31,615 LKDs between January 2010 and
      June 2015, comparing proportions of complete and timely LDF form submissions
      before and after policy implementation. We also used multilevel logistic
      regression to assess donor- and center-level characteristics associated with
      complete and timely LDF submissions. Complete and timely 2-year LDF increased
      from 33% prepolicy (January 2010 through January 2013) to 54% postpolicy
      (February 2013 through June 2015) (p < 0.001). In an adjusted model, the odds of
      2-year LDF increased by 22% per year prepolicy (p < 0.001) and 23% per year
      postpolicy (p < 0.001). Despite these annual increases in LDF, only 43% (87/202)
      of centers met the OPTN/UNOS-required 6-month, 1-year, and 2-year LDF thresholds
      for LKDs who donated in 2013. These findings motivate further evaluation of LDF
      barriers and the optimal approaches to capturing outcomes after living donation.

PMID- 28510357
TI  - KIF11 silencing and inhibition induces chromosome instability that may contribute
      to cancer.
AB  - Understanding the aberrant pathways that contribute to oncogenesis and
      identifying the altered genes involved in these pathways is a critical first step
      to develop effective strategies to better combat cancer. Chromosome instability
      (CIN) is an aberrant phenotype that occurs in ~80% of all cancer types and is
      associated with aggressive tumors, the acquisition of multidrug resistance and
      poor patient prognosis. Despite these associations however, the aberrant genes
      and molecular defects underlying CIN remain poorly understood. KIF11 is an
      evolutionarily conserved microtubule motor protein that functions in centrosome
      and chromosome dynamics in mitosis. Interestingly, the yeast ortholog of KIF11,
      namely CIN8 is a CIN gene and thus aberrant KIF11 expression and function is
      suspected to underlie CIN. In support of this possibility, KIF11 is somatically
      altered in a large number of cancer types. Using a complementary biochemical and
      genetic approach we examined whether KIF11 silencing with siRNAs or inhibition
      with monastrol was able to convert two distinct and karyotypically stable cell
      lines into karyotypically unstable cell lines. Indeed, quantitative imaging
      microscopy and flow cytometry revealed that KIF11 silencing induced increases in
      nuclear areas, micronucleus formation, DNA content and chromosome numbers
      relative to controls that was also observed following KIF11 inhibition.
      Collectively, this study identifies and validates KIF11 as an evolutionarily
      conserved CIN gene, and further suggests that aberrant expression and function
      may contribute to the pathogenesis of a subset of cancers.

PMID- 28510358
TI  - Bottom-Up Design of a Copper-Ruthenium Nanoparticulate Catalyst for Low
      Temperature Ammonia Oxidation.
AB  - A novel nanoparticulate catalyst of copper (Cu) and ruthenium (Ru) was designed
      for low-temperature ammonia oxidation at near-stoichiometric mixtures using a
      bottom-up approach. A synergistic effect of the two metals was found. An optimum
      CuRu catalyst presents a reaction rate threefold higher than that for Ru and
      forty-fold higher than that for Cu. X-ray absorption spectroscopy suggests that
      in the most active catalyst Cu forms one or two monolayer thick patches on Ru and
      the catalysts are less active once 3D Cu islands form. The good performance of
      the tuned Cu/Ru catalyst is attributed to changes in the electronic structure,
      and thus the altered adsorption properties of the surface Cu sites.

PMID- 28510360
TI  - Analysis of Human Papillomavirus Genome Replication Using Two- and Three
      Dimensional Agarose Gel Electrophoresis.
AB  - This unit includes the necessary information to conduct neutral/neutral and
      neutral/alkaline two-dimensional and neutral/neutral/alkaline three-dimensional
      agarose gel electrophoresis. The methodology has been optimized over the years to
      gain a better outcome from the hard-to-interpret signals of human papilloma virus
      replication intermediates obtained from two- and three-dimensional agarose gels.
      Examples of typical results and interpretation of replication intermediate
      patterns are included, and the outcomes of multiple-dimension assays are assessed
      using previously published experimental data. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28510359
TI  - Isolation, Culture and Cryopreservation of Sarcocystis species.
AB  - More than 200 valid Sarcocystis species have been described in the
      parasitological literature. The developmental life cycle in the intermediate host
      and definitive host has only been described for a few species. Sarcocystis
      parasites are common pathogens infecting a wide range of animals, including
      humans, and this unit reviews the methods used for isolating infective stages of
      the parasite from both definitive and intermediate host(s), as well as methods
      used to initiate cultures from sporocysts and merozoites and for cryopreservation
      of various Sarcocystis spp. These methods are based on published reports and our
      experience with Sarcocystis species in cell culture over many years. The
      information presented is suitable for the efficient culture of many Sarcocystis
      species; however, some minor modifications may be needed based on the unique
      developmental patterns of some species. (c) 2017 by John Wiley & Sons, Inc.

PMID- 28510361
TI  - Chlamydia trachomatis Transformation and Allelic Exchange Mutagenesis.
AB  - Gene inactivation is essential for forward and reverse genetic approaches to
      establish protein function. Techniques such as insertion or chemical mutagenesis
      have been developed to mutagenize chlamydiae via targeted or random mutagenesis,
      respectively. Both of these approaches require transformation of chlamydiae to
      either introduce insertion elements or complement mutants. We have recently
      developed a targeted mutagenesis strategy, fluorescence-reported allelic exchange
      mutagenesis (FRAEM), to delete Chlamydia trachomatis L2 genes. This approach
      overcomes several barriers for genetically manipulating intracellular bacteria.
      Perhaps most significantly, FRAEM employs fluorescence reporting to indicate
      successful transformation and subsequent recombination events. Three protocols
      are provided that detail methods to construct gene-specific suicide vectors,
      transform C. trachomatis L2 to select for recombinants, and isolate clonal
      populations via limiting dilution. In aggregate, these protocols will allow
      investigators to engineer C. trachomatis L2 strains carrying complete deletions
      of desired gene(s). (c) 2017 by John Wiley & Sons, Inc.

PMID- 28510362
TI  - Burkholderia thailandensis: Genetic Manipulation.
AB  - Burkholderia thailandensis is a Gram-negative bacterium endemic to Southeast
      Asian and northern Australian soils. It is non-pathogenic; therefore, it is
      commonly used as a model organism for the related human pathogens Burkholderia
      mallei and Burkholderia pseudomallei. B. thailandensis is relatively easily
      genetically manipulated and a variety of robust genetic tools can be used in this
      organism. This unit describes protocols for conjugation, natural transformation,
      mini-Tn7 insertion, and allelic exchange in B. thailandensis. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 28510364
TI  - Lyophilization of Bdellovibrio bacteriovorus 109J for Long-Term Storage.
AB  - Bdellovibrio bacteriovorus 109J is a Gram-negative predatory bacterium with
      obligate host dependency on other Gram-negative bacteria. This bacteriolytic
      predator collides with, enters, and establishes growth within the prey (host)
      periplasm, eventually lysing the prey cell wall to release fresh, motile B.
      bacteriovorus progeny. Laboratory maintenance of B. bacteriovorus has been
      previously described by other investigators. The protocols included in this unit
      deal with the technique required to lyophilize or freeze dry host-dependent B.
      bacteriovorus. This is an alternative means to frozen glycerol stocks for the
      long-term storage of B. bacteriovorus. It includes the cultivation process and
      methods to lyophilize B. bacteriovorus as well as recommended storage conditions.
      In addition, this unit provides insight on the formulation's shelf-life including
      the time to active culture after reviving lyophilized stocks of B. bacteriovorus
      following short-, medium-, and long-term storage. (c) 2017 by John Wiley & Sons,
      Inc.

PMID- 28510365
TI  - Construction of the Benzomesembrine Skeleton: Palladium(0)-Catalyzed
      Intermolecular Arylative Dearomatization of alpha-Naphthols and Subsequent Aza
      Michael Reaction.
AB  - A novel palladium(0)-catalyzed intermolecular arylative dearomatization of alpha
      naphthols and subsequent aza-Michael reaction is described. Two adjacent
      stereocenters were constructed efficiently through consecutive arylative
      dearomatization and Michael addition reactions. By utilizing this method,
      structurally diverse benzomesembrine derivatives were synthesized with excellent
      yields and chemoselectivity. The benzomesembrine products were shown to undergo
      versatile functional-group transformations.

PMID- 28510363
TI  - Purification Toxoplasma gondii Tissue Cysts Using Percoll Gradients.
AB  - The protozoan parasite Toxoplasma gondii is capable of infecting all warm-blooded
      animals and humans. Infectious, transmissible forms of the parasite include
      oocysts produced by the sexual cycle within the definitive feline host and tissue
      cysts that form Toxoplasma in the central nervous system and muscle during the
      asexual cycle within all chronically infected warm-blooded hosts. These tissue
      cysts are populated with slow-growing bradyzoites, which until recently have been
      thought to be dormant entities in the context of immune sufficiency. Reactivation
      to active growth during immune suppression is of critical clinical importance.
      However, little is known about tissue cysts or the bradyzoites they house, as the
      diversity of tissue cysts cannot be replicated in cell culture systems. This
      protocol for optimization of tissue cyst purification from the brains of infected
      mice using Percoll gradients provides an efficient means to recover in vivo
      derived tissue cysts that can be applied to imaging, cell biological,
      biochemical, transcriptomic, and proteomic analyses. (c) 2017 by John Wiley &
      Sons, Inc.

PMID- 28510367
TI  - Reply.

PMID- 28510366
TI  - HMGA2 plays an important role in Cr (VI)-induced autophagy.
AB  - Cr (VI) is mutagenic and carcinogenic, but the mechanism is unclear. In this
      study, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-induced
      autophagy was investigated. Cr (VI) treatment induced formation of
      autophagosomes, increased expression of LC3II, Atg12-Atg5, Atg4, Atg10, HMGA1 and
      HMGA2 proteins, and decreased the expression of p62 in A549 cells. Silencing of
      HMGA2 gene by siRNA blocked Cr (VI)-induced formation of autophagosomes,
      expression of LC3II, Atg12-Atg5, Atg10 and reduction of p62. Overexpression of
      HMGA2 in HEK 293 and HeLa cells could induce the expression of LC3II, Atg12-Atg5
      and Atg10, and decrease the expression of p62. Although the protein level of
      Atg12-Atg5 conjugation changed after Cr (VI) treatment, silencing of HMGA2 and
      overexpression of HMGA2, both the proteins and mRNA levels of Atg12 and Atg5 were
      not changed significantly. ChIP assay demonstrated that HMGA2 protein directly
      bound to the promoter sequence of Atg10 gene, which modulated the conjugation of
      Atg12-Atg5. Interestingly, 3-MA markedly prevented Cr (VI)-induced cell growth of
      A549 cells. Our further in vivo study confirmed that the expression of HMGA1,
      HMGA2, LC3II, Atg12-Atg5, Atg4, Atg5, Atg7, Atg10, Atg12, Beclin 1 were increased
      and p62 was reduced in lung tissues of Cr (VI)-treated BALB/c mice. Combining,
      our data demonstrated that HMGA2 plays an important role in Cr (VI)-induced
      autophagy and the mechanism underlies Atg12-Atg5 conjugation modulated by HMGA2
      dependent transcriptional regulation of Atg10. This suggests that HMGA2 might be
      an important biomarker in Cr (VI)-induced autophagy, cell-growth or other
      toxicities.

PMID- 28510368
TI  - Escalator-related injuries in 30 dogs (2007-2014).
AB  - OBJECTIVE: To describe a population of dogs affected by escalator-related
      injuries, and to characterize the types of injuries sustained and describe
      treatment administered. DESIGN: Retrospective study from March 2007 to November
      2014. SETTING: Large urban referral and emergency facility. ANIMALS: Thirty
      client-owned dogs presenting with injuries acquired while riding an escalator.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All injuries in this study
      occurred secondary to entrapment of 1 or more paws in the moving parts of an
      escalator; 39 paws were injured in total. The median body weight of the patients
      in this study was 4.25 kg, with 73.3% of the patients weighing less than 10 kg.
      Fifteen patients (50.0%) were treated surgically, the remainder were managed
      conservatively. Eight patients (26.7%) underwent digit or partial-digit
      amputation. Of the conservatively managed patients, 10 were treated with
      bandaging of the wounds. Antimicrobials, opiate analgesics, and nonsteroidal anti
      inflammatory drugs were administered in both surgically and conservatively
      managed patients. CONCLUSIONS: While uncommon, escalator accidents can result in
      significant injury to dogs. Measures can be taken to prevent these injuries from
      occurring, whether through client education, dog training, structural
      modifications in the escalators themselves, or avoidance of escalators. In the
      present study, the survival rate of dogs injured on escalators was 100%.

PMID- 28510369
TI  - Letter to the Editor: Radiation Injuries: Reemphasizing the Usage of Radiation
      Protection Prosthesis.
AB  - Sir, I write in regard to Nayar S et al article 'The Effect of a Radiation
      Positioning Stent (RPS) in the Reduction of Radiation Dosage to the Opposing Jaw
      and Maintenance of Mouth opening after Radiation Therapy'. I wholeheartedly agree
      to that patients undergoing radio-therapy who had an Radiation Positioning Stent
      (RPS) would show a significant reduction in radiation dosage to the opposing jaw
      and maintained their mouth opening in the short-term. As we know that oral cancer
      has emerged to be one of most deadliest cancer nowadays.

PMID- 28510370
TI  - Titanium Corrosion: Implications For Dental Implants.
AB  - Titanium has been considered as one of the most biocompatible metals. Studies
      testing its corrosion resistance have proposed that the titanium oxide layer
      formed on the metal surface is lost under certain unavoidable conditions to which
      it is exposed in the oral environment. This questions its property of corrosion
      resistance in the oral cavity. Hence, there is a need to understand the
      mechanisms of corrosion, which can help in the long-term stability and function
      of implants. Here, we review the possible pathways of corrosion of titanium in
      the oral cavity, its implications and proposed methods of prevention of
      corrosion.

PMID- 28510371
TI  - Effect of Implant Diameter And Alloy on Peri-Implant Strain: An In Vitro
      Quantitative Strain Analysis.
AB  - This study aimed to evaluate the impact of implant diameter and alloy on peri
      implant strains. Three implant types were investigated: regular commercially pure
      titanium (RcpTi), narrow commercially pure titanium (NcpTi) and narrow titanium
      zirconium alloy (NTi-Zr) implants. Strain gauge models were fabricated from epoxy
      resin. All the implants were loaded in identical fashion. The greatest peri
      implant strains were recorded around NTi-Zr implants, followed by NcpTi implants.
      The RcpTi implants were associated with the least strain values. The difference
      between the implant types was significant. Therefore, it can be concluded that
      the implant diameter and material can influence the peri-implant strain
      magnitude.

PMID- 28510372
TI  - Does Ferrule Effect Affect Implant-Abutment Stability?
AB  - PURPOSE: This study investigated the influence of placing implant-supported
      crowns on the torque loss of the abutment screw before and after loading.
      MATERIAL AND METHODS: Twenty implant-abutment assemblies were randomly assigned
      to two groups. The first group was consisted of abutments with abutment-level
      finishing line (abutment-level), and in the second group the crown margin was
      placed on the implant shoulder (implant-level). Initial torque loss was recorded
      for all specimens. After 500000 cyclic load of 75 N and frequency of 2 Hz, post
      loading torque loss was recorded. Finite element model of each group was also
      modeled and screw energy, and stress were analyzed and compared between two
      groups. RESULTS: ANOVA for repeated measurements showed that the torque loss did
      not change significantly after cyclic loading (P=0.73). Crown margin also had no
      significant effect on the torque loss (P=0.56). However, the energy and stress of
      screw in abutment-level model (4.49 mJ and 22.74 MPa) was higher than implant
      level model (3.52 mJ and 20.81 MPa). CONCLUSIONS: Although embracing the implant
      with crown produced less stress and energy in the abutment-implant screw, it did
      not have any significant influence on the torque loss of the screw.

PMID- 28510373
TI  - Acrylic Reinforcement with Off the Shelf Perforated Metal Plates.
AB  - : To evaluate the effect of Dentaurum Grid Strengthener on flexural strength and
      modulus of two types of PMMA, 24 beams (75 mm x 10 mm x 2.5 mm) containing bonded
      and flattened Grid Strengthener and 24 beams without Grid Strengthener were
      subjected to a 3-point bending test at 5 mm/min. Flexural strength and modulus
      were calculated. Data were analyzed with a 2-way ANOVA. The highest mean strength
      and flexural modulus was measured for reinforced high impact resin (96.2+/-14.3
      MPa and 3425+/-779 MPa, respectively). For flexural strength and modulus, resin
      and reinforcement had a significant effect. CLINICAL RELEVANCE: Independent of
      the resin used, the incorporation of a grid strengthener increases the strength
      and modulus, thus the fracture probability of dentures is reduced.

PMID- 28510374
TI  - Qualitative Beam Profiling of Light Curing Units for Resin Based Composites.
AB  - This study investigates two technically simple methods to determine the
      irradiance distribution of light curing units that governs the performance of a
      visible-light curing resin-based composites. Insufficient light irradiation leads
      to under-cured composites with poor mechanical properties and elution of residual
      monomers. The unknown irradiance distribution and its effect on the final
      restoration are the main critical issues requiring highly sophisticated
      experimental equipment. The study shows that irradiance distributions of LCUs can
      easily be determined qualitatively with generally available equipment. This
      significantly helps dentists in practices to be informed about the homogeneity of
      the curing lights.

PMID- 28510375
TI  - The Effect of Irradiation Distance on Light Transmittance and Vickers Hardness
      Ratio of Two Bulk-fill Resin-based Composites.
AB  - The aims of this study were to assess the light energy transmission and Vickers
      hardness (VH) ratio of two bulk-fill resin-based composites (RBCs) (Tetric
      EvoCeram and Filtek) cured at different distances between the light curing unit's
      (LCU) tip and the surface of the restoration (T-S) using either a Bluephase G2,
      Bluephase(r) 'turbo tip' or Bluephase Style LCU. Samples were cured from the top
      at T-S distances of 2mm, 6mm and 10mm for 20 seconds. A MARC-Resin-CalibratorTM
      recorded the transmitted irradiance reaching the bottom of the sample, in real
      time. The VH was measured at the top and bottom after 24h of dark storage. Both
      the total light energy (TLE) transmitted through the samples and their VH ratios
      were reduced with increasing T-S distance. At 10mm T-S distance, the VH ratio
      values of samples cured with Bluephase G2 LCU were significantly greater than the
      samples cured with the other LCUs while the samples cured with Bluephase(r)
      'turbo tip' showed the lowest values. It can be concluded that TLE transmitted
      through bulk-fill RBCs and their VH ratio reduces with increasing T-S distance
      but the rate of decline is LCU dependent. Bluephase G2 was associated with the
      smallest light attenuation.

PMID- 28510376
TI  - One-Piece Implant-Retained Mandibular Overdentures By Pre-Fabricated Titanium
      Telescopic Attachments and Frictional Varnish: A Two-Year Prospective Study.
AB  - Clinical efficiency of one-piece screw-type implants with telescopic were
      attachments evaluated in this study. Twenty-four patients received a mandibular
      implant-supported overdenture and maxillary complete denture. Ninety-six one
      piece implants were inserted in the inter-foraminal area. Implants were
      immediately loaded with an implant-retained overdenture and telescopic
      attachments which had frictional retention elements. There was 0.25+/-0.24 mm,
      0.32+/-0.25 mm, 0.43+/-0.30 mm, 0.61+/-0.30 mm and of bone resorption after 3, 6,
      12 and 24 months, respectively. The need to activate the frictional retention was
      the most common complication. Treatment outcomes for prefabricated telescopic
      retained overdentures on one-piece implants are similar to that obtained in cases
      of delayed loading.

PMID- 28510377
TI  - Retrospective Study of the Survival and Patient Satisfaction with Composite Dahl
      Restorations in the Management of Localised Anterior Tooth Wear.
AB  - OBJECTIVE: This retrospective study was undertaken to evaluate the clinical
      performance of direct composite restorations placed at an increased vertical
      dimension to manage localised anterior tooth wear using the Dahl approach.
      SUBJECTS AND METHODS: Two hundred and ninety six restorations were placed at an
      increased OVD in 41 subjects with localized anterior Tooth Surface Loss (TSL)
      were included. Survival analysis was carried out at three levels, major failure
      only, minor failure only and all types of failure. Clinical follow up showed that
      the posterior occlusion was reformed after a mean duration of 25.4 months (range
      6 to 60 months). Mean clinical follow up of 25.4 months showed a success rate of
      88.8% and survival rate of 95.6% of the restorations. The major failure rate was
      4.4% while the minor failure rate was 8.7%. Patients' reported a significant
      improvement in appearance, and self-confidence and reduction in sensitivity. Self
      reported patient satisfaction with the procedure was high. CLINICAL RELEVANCE:
      Placement of resin-based composite restorations at an increased occlusal vertical
      dimension to manage localised anterior tooth wear has a good short to medium term
      survival.

PMID- 28510378
TI  - Replantation surgery

PMID- 28510415
TI  - Smart Reinvention of the Contact Lens with Graphene.
AB  - With potential benefits to the 71 million contact lens users worldwide, contact
      lenses are being reinvented in the form of smart wearable electronics. In this
      issue of ACS Nano, Lee et al. report on the fascinating functions of a graphene
      based smart contact lens that is able to protect eyes from electromagnetic waves
      and dehydration. Graphene and two-dimensional materials can be exploited in many
      opportunities in the development of smart contact lenses. Here, we briefly review
      and describe prospects for the future of smart contact lenses that incorporate
      graphene in their platforms.

PMID- 28510417
TI  - Correction to "Classics in Chemical Neuroscience: Haloperidol".

PMID- 28510416
TI  - Optical Asymmetry and Nonlinear Light Scattering from Colloidal Gold Nanorods.
AB  - A systematic study is presented of the intensity-dependent nonlinear light
      scattering spectra of gold nanorods under resonant excitation of the longitudinal
      surface plasmon resonance (SPR). The spectra exhibit features due to coherent
      second and third harmonic generation as well as a broadband feature that has been
      previously attributed to multiphoton photoluminescence arising primarily from
      interband optical transitions in the gold. A detailed study of the spectral
      dependence of the scaling of the scattered light with excitation intensity shows
      unexpected scaling behavior of the coherent signals, which is quantitatively
      accounted for by optically induced damping of the SPR mode through a Fermi liquid
      model of the electronic scattering. The broadband feature is shown to arise not
      from luminescence, but from scattering of the second-order longitudinal SPR mode
      with the electron gas, where efficient excitation of the second order mode arises
      from an optical asymmetry of the nanorod. The electronic-temperature-dependent
      plasmon damping and the Fermi-Dirac distribution together determine the intensity
      dependence of the broadband emission, and the structure-dependent absorption
      spectrum determines the spectral shape through the fluctuation-dissipation
      theorem. Hence a complete self-consistent picture of both coherent and incoherent
      light scattering is obtained with a single set of physical parameters.

PMID- 28510418
TI  - Conjugation Reaction with 8-Arm PEG Markedly Improves the Immunogenicity of
      Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein.
AB  - Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for
      tuberculosis (TB). Effective vaccination is highly desired for immunoprotection
      against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb
      secreted protein antigens, which suffer from poor immunogenicity. Thus, an
      antigen delivery system and adjuvants are needed to improve the immunogenicity of
      the two proteins. A CFP10-TB10.4 fusion protein (CT) was used as the antigen in
      the present study. Conjugation of 4-6 CT molecules in one entity with 8-arm
      polyethylene glycol (PEG) acted as an antigen delivery system. Aluminum
      loxoribine mixture (A-L) and poly(I:C) functioned as the adjuvants. As compared
      with CT, the polymerized CT (CT-PEG) elicited significantly higher CT-specific
      IgG titers, higher Th1- and Th2-type cytokines and higher percentages of CD4+ IFN
      gamma+ and CD4+ IL-4+ cells in BALB/c mice. The presence of A-L and poly(I:C)
      could both increase the immune response to CT-PEG. Conjugation reaction with 8
      arm PEG showed a predominant driving force to improve the immunogenicity of CT.
      Pharmacokinetic study in SD rats revealed that conjugation reaction with 8-arm
      PEG prolonged the systemic circulation of CT and exposure to the immune system.
      CT-PEG with A-L showed no apparent toxicity to organs, whereas CT-PEG with
      poly(I:C) displayed some toxicity to organs. Thus, an effective and safe vaccine
      against Mtb infection could be rationally designed by conjugation reaction of Mtb
      secreted protein antigen with 8-arm PEG and subsequent addition of A-L.

PMID- 28510419
TI  - Sunlight Promotes Fast Release of Hazardous Cadmium from Widely-Used Commercial
      Cadmium Pigment.
AB  - Cadmium pigments are widely used in the polymer and ceramic industry. Their
      potential environmental risk is under debate, being the major barrier for
      appropriate regulation. We show that 83.0 +/- 0.2% of hazardous cadmium ion
      (Cd2+) was released from the commercial cadmium sulfoselenide pigment (i.e.,
      cadmium red) in aqueous suspension within 24 h under simulated sunlit conditions.
      This photodissolution process also generated sub-20 nm pigment nanoparticles.
      Cd2+ release is attributed to the reactions between photogenerated holes and the
      pigment lattices. The photodissolution process can be activated by both
      ultraviolet and visible light in the solar spectrum. Irradiation under alkaline
      conditions or in the presence of phosphate and carbonate species resulted in
      reduced charge carrier energy or the formation of insoluble and photostable
      cadmium precipitates on pigment surfaces, mitigating photodissolution. Tannic
      acid inhibited the photodissolution process by light screening and scavenging
      photogenerated holes. The fast release of Cd2+ from the pigment was further
      confirmed in river water under natural sunlight, with 38.6 +/- 0.1% of the
      cadmium released within 4 h. Overall, this study underscores the importance to
      account for photochemical effects to inform risk assessments and regulations of
      cadmium pigments which are currently based on their low solubility.

PMID- 28510420
TI  - Nontarget Analysis Reveals a Bacterial Metabolite of Pyrene Implicated in the
      Genotoxicity of Contaminated Soil after Bioremediation.
AB  - Bioremediation is an accepted technology for cleanup of soil contaminated with
      polycyclic aromatic hydrocarbons (PAHs), but it can increase the genotoxicity of
      the soil despite removal of the regulated PAHs. Although polar biotransformation
      products have been implicated as causative genotoxic agents, no specific product
      has been identified. We pursued a nontarget analytical approach combining effect
      directed analysis (EDA) and metabolite profiling to compare extracts of PAH
      contaminated soil from a former manufactured-gas plant site before and after
      treatment in a laboratory-scale aerobic bioreactor. A compound with the
      composition C15H8O2 and four methylated homologues were shown to accumulate as a
      result of bioreactor treatment, and the C15H8O2 compound purified from soil
      extracts was determined to be genotoxic. Its structure was established by nuclear
      magnetic resonance and mass spectroscopy as a heretofore unidentified alpha,beta
      unsaturated lactone derived from dioxygenation of pyrene at an apical ring, 2H
      naphtho[2,1,8-def]chromen-2-one (NCO), which was confirmed by synthesis. The
      concentration of NCO in the bioreactor was 11 MUg g-1 dry soil, corresponding to
      13% of the pyrene removed. It also accumulated in aerobically incubated soil from
      two additional PAH-contaminated sites and was formed from pyrene by two pyrene
      degrading bacterial cultures known to be geographically widespread, underscoring
      its potential environmental significance.

PMID- 28510421
TI  - Converting Carbohydrates to Carbon-Based Photocatalysts for Environmental
      Treatment.
AB  - Carbohydrates in biomass can be converted to semiconductive hydrothermal
      carbonation carbon (HTCC), a material that contains plenty of sp2-hybridization
      structures. Under solar light illumination, HTCC generates photoexcited
      electrons, holes, and hydroxyl radicals. These species can be used for
      photocatalytic treatment such as water disinfection and degradation of organic
      pollutants. The photocatalytic activity of HTCC can be significantly enhanced by
      iodine doping. The enhancement mechanism is investigated by density functional
      theoretical calculations and electrochemical measurements. The iodine dopants
      twist and optimize the structures of the sp2-hybridization in HTCC, thereby
      favoring photon-induced excitation. Moreover, the iodine dopants facilitate the
      charge transfer between different sp2-hybridization structures, thus increasing
      the conductivity and activity of the HTCC. An added benefit is that the I-doped
      HTCC exhibits lower cytotoxic effect than the pure HTCC. In addition to
      monosaccharides (glucose), disaccharides (sucrose), and polysaccharides (starch),
      we have also transformed crops (e.g., rice), plants (e.g., grass), and even
      agricultural waste (e.g., straw) and animal waste (e.g., cow dung). The
      conversion of carbohydrates to HTCC may be considered as a "Trash to Treasure"
      approach. We believe this discovery will attract a lot of attention from
      researchers involved in environmental catalysis, waste recycling, and pollution
      treatment.

PMID- 28510422
TI  - Encapsulation of Platinum in Fullerenes: Is That Possible?
AB  - Whether transition metals can be entrapped inside fullerenes has remained unclear
      for a long time. Here mass spectrometric proof of entrapment of the group VIII
      transition-metal platinum (Pt) in fullerenes is first reported. Theoretical
      calculations on the example of La2PtC90 show that La2Pt@C2(99915)-C90 is the most
      stable isomer. Unlike other reported endohedral metal atoms, the entrapped Pt
      atom is negatively charged. This work provides valuable clues for the synthesis
      of some important missing endohedral metallofullerenes.

PMID- 28510423
TI  - Phycocyanin-Functionalized Selenium Nanoparticles Reverse Palmitic Acid-Induced
      Pancreatic beta Cell Apoptosis by Enhancing Cellular Uptake and Blocking Reactive
      Oxygen Species (ROS)-Mediated Mitochondria Dysfunction.
AB  - Accumulation of palmitic acid (PA) in human bodies could cause damage to
      pancreatic beta cells and lead to chronic diseases by generation of reactive
      oxygen species (ROS). Therefore, it is of great significance to search for
      nutrition-available agents with antioxidant activity to protect pancreatic islet
      cells against PA-induced damage. Phycocyanin (PC) and selenium (Se) have been
      reported to have excellent antioxidant activity. In this study, PC-functionalized
      selenium nanoparticles (PC-SeNPs) were synthesized to investigate the in vitro
      protective effects on INS-1E rat insulinoma beta cells against PA-induced cell
      death. A potent protective effect was achieved by regulation of particle size and
      PC content. Among three PC-SeNPs (165, 235, and 371 nm), PC-SeNPs-235 nm showed
      the highest cellular uptake and the best protective activities. For cell cycle
      analysis, PC-SeNPs showed a better protective effect on PA-induced INS-1E cell
      apoptosis than PC or SeNPs, and PC-SeNPs-235 nm exhibited the best effect.
      Further mechanistic studies demonstrated that PA induced overproduction of
      intracellular ROS, mitochondria fragmentation, activation of caspase-3, -8, and 
      9, and cleavage of PARP. However, pretreatment of the cells with PC-SeNPs
      effectively blocked these intracellular events, which suggests that PC-SeNPs
      could protect INS-1E cells against PA-induced cell apoptosis via attenuating
      oxidative stress and downstream signaling pathways. This finding provides a great
      promising nutritional approach for protection against diseases related to islet
      damage.

PMID- 28510425
TI  - Switching of Resistive Memory Behavior from Binary to Ternary Logic via
      Alteration of Substituent Positioning on the Subphthalocyanine Core.
AB  - Two new axially or peripherally functionalized subphthalocyanines with the
      decoration of donor-acceptor substituents have been successfully synthesized,
      characterized and employed in the application of resistive memory device via
      solution-processable technique. Axially substituted subphthalocyanine shows
      ternary resistive memory behavior with well-separated current ratios of 1:106:108
      between "OFF", "ON1" and "ON2" states, while only binary logic is observed for
      peripherally substituted subphthalocyanine. Computational studies show the
      presence of two well-separated charge transfer states in the axially substituted
      subphthalocyanine, while the charge transfer processes between the peripheral
      substituents and the subphthalocyanine core are found to be very close in energy.
      This work has demonstrated the impact of the substituent positioning on the
      subphthalocyanine-based memory device performance, providing a new research
      dimension for the future design and development of multistate organic resistive
      memory.

PMID- 28510424
TI  - Structure-Dependent Binding of hnRNPA1 to Telomere RNA.
AB  - Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs
      various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an
      RNA-binding protein involved in the telomere maintenance machinery. To date,
      little is known about how hnRNPA1 binds to telomeric RNA. In this study, we
      investigated the binding affinity and recognition mechanism of telomere RNA with
      the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking
      method, we showed that the telomere RNA G-quadruplex with loops is important in
      the interaction of telomere RNA with hnRNPA1. Using small-molecule probes, we
      directly visualized the complex formed by the telomere RNA G-quadruplex and
      hnRNPA1 in vitro and in live cells. The results suggested that the structure
      dependent binding of hnRNPA1 to telomere RNA regulates the telomere function.
      Therefore, our study provides new insights into the interactions between the RNA
      G-quadruplex and proteins at the telomere.

PMID- 28510427
TI  - Single Crystal Proton Conduction Study of a Metal Organic Framework of Modest
      Water Stability.
AB  - A sulfonated indium (In) metal organic framework (MOF) is reported with an
      anionic layered structure incorporating hydrogen-bonded dimethylammonium cations
      and water molecules. The MOF becomes amorphous in >60% relative humidity;
      however, impedance analysis of pelletized powders revealed a proton conduction
      value of over 10-3 S cm-1 at 25  degrees C and 40% RH, a very high proton
      conduction value for low humidity and moderate temperature. Given the modest
      humidity stability of the MOF, triaxial impedance analyses on a single crystal
      was performed and confirmed bulk proton conductivity over 10-3 S cm-1 along two
      axes corroborating the data from the pellet.

PMID- 28510426
TI  - Multivariate Analyses of Phytoplankton Pigment Fluorescence from a Freshwater
      River Network.
AB  - Monitoring phytoplankton classes in river networks is critical to understanding
      phytoplankton dynamics and to predicting the ecosystem response to changing land
      use and seasons. Applicability of phytoplankton fluorescence as a quick and
      effective ecological monitoring approach is relatively unexplored in freshwater
      ecosystems. We used multivariate analyses of fluorescence from pigment extracted
      in 90% acetone to assess the variability in phytoplankton classes, herbivory, and
      organic matter quality in a freshwater river network. A total of four models
      developed by the parallel factor analysis (PARAFAC) of fluorescence excitation
      and emission matrices identified six components: Model 1 (pheophytin-A and
      chlorophyll-A), Model 2 (chlorophyll-B and chlorophyll-C), Model 3 (pheophytin
      B), and Model 4 (pheophytin-C). Redundancy analyses revealed that in the summer,
      urban and agricultural streams were abundant in chlorophylls, fresh organic
      matter, and organic nitrogen, whereas in winter, streams were high in
      phaeopigments. A slow-moving, light-limited wetland stream was an exception as
      high phaeopigment abundance was observed in both seasons. The PARAFAC components
      were used to develop a partial least-squares regression-based model (r2 = 0.53;
      Nash-Sutcliffe efficiency = 0.5; n = 147) that successfully predicted chlorophyll
      A concentrations from an external subset of river water samples (r2 = 0.41; p <
      0.0001; n = 75). Thus, combining multivariate analyses and fluorescence
      spectroscopy is useful for monitoring and predicting phytoplankton dynamics in
      large river networks.

PMID- 28510428
TI  - Statistical Analysis and Prediction of Covalent Ligand Targeted Cysteine
      Residues.
AB  - Targeted covalent compounds or drugs have good potency as they can bind to a
      specific target for a long time with low doses. Most currently known covalent
      ligands were discovered by chance or by modifying existing noncovalent compounds
      to make them covalently attached to a nearby reactive residue. Computational
      methods for novel covalent ligand binding prediction are highly demanded. We
      performed statistical analysis on protein complexes with covalent ligands
      attached to cysteine residues. We found that covalent modified cysteine residues
      have unique features compared to those not attached to covalent ligands,
      including lower pKa, higher exposure, and higher ligand binding affinity. SVM
      models were built to predict cysteine residues suitable for covalent ligand
      design with prediction accuracy of 0.73. Given a protein structure, our method
      can be used to automatically detect druggable cysteine residues for covalent
      ligand design, which is especially useful for identifying novel binding sites for
      covalent allosteric ligand design.

PMID- 28510429
TI  - Copolymerization of Carbon Dioxide with Epoxides Catalyzed by Structurally Well
      Characterized Dinickel Bis(benzotriazole iminophenolate) Complexes: Influence of
      Carboxylate Ligands on the Catalytic Performance.
AB  - A series of structurally well-defined dinickel carboxylate complexes based on the
      RBiIBTP derivatives [RBiIBTP = bis(benzotriazole iminophenolate), where R = 3C
      for the propyl-bridged backbone and 5C for the 2,2-dimethyl-1,3-propyl-bridged
      backbone] were synthesized and developed for copolymerization of CO2 and
      epoxides. The one-pot reactions of nickel perchlorate with the RBiIBTP-H2
      proligands and an appropriate amount of carboxylic acid derivatives (CF3COOH or 4
      X-C6H4CO2H; X = H, CF3, OMe) upon the addition of triethylamine in refluxing
      methanol (MeOH) afforded dinuclear nickel dicarboxylate complexes, which could be
      formulated as either [(RBiIBTP)Ni2(O2CCF3)2] (1 and 2) or [(RBiIBTP)Ni2(O2CC6H4-4
      X)2] (3-7). The dinickel monobenzoate complexes [(RBiIBTP)Ni2(O2CPh)(ClO4)(H2O)]
      [R = 3C (8) and 5C (9)] were prepared by using a similar synthetic route in
      tetrahydrofuran under reflux with a ligand precursor to metal salt to benzoic
      acid ratio of 1:2:1 in the presence of NEt3. Recrystallization of neutral nickel
      perchlorate complex 8 in a saturated MeOH or ethanol (EtOH) solution gave ionic
      and alcohol-solvated monobenzoate bimetallic analogues
      [(3CBiIBTP)Ni2(O2CPh)(S)2]ClO4, where S = MeOH (10) and EtOH (11). Single-crystal
      X-ray crystallography of dinickel analogues 1-11 indicates that the BiIBTP
      scaffold performs as a N,O,N,N,O,N-hexadentate ligand to chelate two Ni atoms,
      and the ancillary carboxylate group adopts a bridging bidentate bonding mode.
      Catalysis for copolymerization of carbon dioxide (CO2) with cyclohexene oxide
      (CHO) by complexes 1-9 was systematically investigated, and the influence of
      carboxylate ligands on the catalytic behavior was also studied. Trifluoroacetate
      ligated dinickel complex 1 efficiently catalyzed CO2 and CHO with a high turnover
      frequency (>430 h-1) in a controlled fashion, generating perfectly alternating
      poly(cyclohexenecarbonate) with large molecular weight (Mn > 50000 g/mol). In
      addition to CO2/CHO copolymerization, bimetallic complex 1 was found to
      effectively copolymerize CO2 with 4-vinyl-1,2-cyclohexene oxide (VCHO) or
      cyclopentene oxide, producing the high carbonate contents of poly(VCHC-co-VCHO)s
      and highly alternating poly(cyclopentene carbonate)s, respectively. This study
      also enabled us to compare the catalytic efficiency of using cyclic epoxides with
      different ring strains or functional groups as comonomers by the dinickel
      catalyst 1.

PMID- 28510431
TI  - Photocatalytic Hydrogen Production Using a Red-Absorbing Ir(III)-Co(III) Dyad.
AB  - The synthesis of a Ir(III)-Co(III) dyad with vectorial electron transfer afforded
      a novel supramolecular system that photocatalytically produces hydrogen in a
      range extending from the blue region of the spectrum to the red region with
      higher turnover number and frequency compared to other bimetallic dyads.

PMID- 28510430
TI  - Nanoarchitecturing of Natural Melanin Nanospheres by Layer-by-Layer Assembly:
      Macroscale Anti-inflammatory Conductive Coatings with Optoelectronic Tunability.
AB  - Natural melanins are biocompatible conductors with versatile functionalities.
      Here, we report fabrication of multifunctional poly(vinyl alcohol)/melanin
      nanocomposites by layer-by-layer (LBL) assembly using melanin nanoparticles
      (MNPs) directly extracted from sepia officinalis inks. The LBL assembly offers
      facile manipulation of nanotextures as well as nm-thickness control of the
      macroscale film by varying solvent qualities. The time-resolved absorption was
      monitored during the process and quantitatively studied by fractal dimension and
      lacunarity analysis. The capability of nanoarchitecturing provides confirmation
      of complete monolayer formation and leads to tunable iridescent reflective colors
      of the MNP films. In addition, the MNP films have durable electrochemical
      conductivities as evidenced by enhanced charge storage capacities for 1000
      cycles. Moreover, the MNP covered ITO (indium tin oxide) substrates significantly
      reduced secretion of inflammatory cytokines, TNF-alpha, by raw 264.7 macrophage
      cells compared to bare ITO, by a factor of 5 and 1.8 with and without
      lipopolysaccharide endotoxins, respectively. These results highlight the
      optoelectronic device-level tunability along with the anti-inflammatory
      biocompatibility of the MNP LBL film. This combination of performance should make
      these films particularly interesting for bioelectronic device applications such
      as electroceuticals, artificial bionic organs, biosensors, and implantable
      devices.

PMID- 28510432
TI  - Diels-Alder Cycloaddition of Cyclopentadiene and C60 at the Extreme High
      Pressure.
AB  - High-pressure Diels-Alder cycloaddition reaction of fullerenes is an important
      synthetic method for the thermally stable cycloadducts. The effects of high
      pressure on the potential energy surfaces of Diels-Alder cycloaddition of
      cyclopentadiene and C60 were studied with a recently developed approach, the
      polarizable continuum model for extreme pressure (XP-PCM). It is revealed that
      the high pressure reduces the activation energies and increases reaction energies
      drastically, making the DA reaction more favorable. The pressure effects on the
      reaction energetics can be divided into the cavitation and electronic
      contributions. For the activation energy, the cavitation contribution is
      significant in comparison with the electronic contribution. To assist future
      experiments, the activation volume and reaction volume were computed on the basis
      of the relationship between activation energy or reaction energy with the
      pressure as a consequence of the fitting linear correlation between activation
      energy or reaction energy with the pressure.

PMID- 28510434
TI  - Mechanistic Description of Photochemical Oligomer Formation from Aqueous Pyruvic
      Acid.
AB  - The aqueous phase photochemistry of pyruvic acid, an important oxidation product
      of isoprene, is known to generate larger oligomeric species that may contribute
      to the formation of secondary organic aerosol in the atmosphere. Using high
      resolution negative mode electrospray ionization mass spectrometry, the aqueous
      photochemistry of dilute solutions of pyruvic acid (10, 1, and 0.5 mM) under
      anaerobic conditions was investigated. Even at the lowest concentration,
      covalently bonded dimers and trimers of pyruvic acid were observed as
      photochemical products. We calculate that it is energetically possible to
      photochemically generate parapyruvic acid, a dimer of pyruvic acid that is known
      to form via dark oligomerization processes. Subsequent photochemical reactions of
      parapyruvic acid with pyruvic acid form larger oligomeric products, such as 2,4
      dihydroxy-2-methyl-5-oxohexanoic acid. A robust and relatively simple
      photochemical mechanism is discussed that explains both the conditional
      dependence and wide array of products that are observed.

PMID- 28510433
TI  - Gibbs Sampler-Based lambda-Dynamics and Rao-Blackwell Estimator for Alchemical
      Free Energy Calculation.
AB  - lambda-dynamics is a generalized ensemble method for alchemical free energy
      calculations. In traditional lambda-dynamics, the alchemical switch variable
      lambda is treated as a continuous variable ranging from 0 to 1 and an empirical
      estimator is utilized to approximate the free energy. In the present article, we
      describe an alternative formulation of lambda-dynamics that utilizes the Gibbs
      sampler framework, which we call Gibbs sampler-based lambda-dynamics (GSLD).
      GSLD, like traditional lambda-dynamics, can be readily extended to calculate free
      energy differences between multiple ligands in one simulation. We also introduce
      a new free energy estimator, the Rao-Blackwell estimator (RBE), for use in
      conjunction with GSLD. Compared with the current empirical estimator, the
      advantage of RBE is that RBE is an unbiased estimator and its variance is usually
      smaller than the current empirical estimator. We also show that the multistate
      Bennett acceptance ratio equation or the unbinned weighted histogram analysis
      method equation can be derived using the RBE. We illustrate the use and
      performance of this new free energy computational framework by application to a
      simple harmonic system as well as relevant calculations of small molecule
      relative free energies of solvation and binding to a protein receptor. Our
      findings demonstrate consistent and improved performance compared with
      conventional alchemical free energy methods.

PMID- 28510435
TI  - Carbenes as Electron-Pair Donors To CO2 for C...C Tetrel Bonds and C-C Covalent
      Bonds.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to identify stable
      complexes and molecules and the transition structures that interconvert them on
      the potential surfaces of ten singlet carbene bases acting as electron-pair
      donors to CO2. The carbene bases include cyclic C(NHCH)2 or NHC, C(NH2)2, an
      oxygen heterocyclic carbene C(OCH)2 or OHC, C(OH)2, C(CH3)2, cyclic C3H2, CCCH2,
      CCl2, CCH2, and CF2. Carbene:CO2 complexes stabilized by C...C tetrel bonds have
      been found on all potential surfaces, whereas carbene-CO2 molecules stabilized by
      C-C covalent bonds have been found on eight surfaces. Three of these molecules
      have open structures with C2v symmetry, whereas the remaining have cyclic three
      membered C-O-C rings with Cs symmetry. The transition structures which connect
      the complex and the molecule are bound on three of the potential surfaces.
      Whether the transition structure is bound or unbound relative to the carbene and
      CO2 depends on the relationship among C-C distances at the three stationary
      points on the surface. Charge-transfer interactions stabilize carbene:CO2
      complexes. The primary charge transfer in complexes arises from electron donation
      from the carbene lone-pair to the CO2 molecule. There is also back-donation of
      charge from CO2 to the carbene in three complexes. Systematic changes in bonding
      properties occur as complexes go through transition structures and become
      molecules. EOM-CCSD inter- and intramolecular C-C and C-O spin-spin coupling
      constants have been computed and compared for complexes and molecules. A search
      of the CSD database found the (NH2)2C-CO2 structure and 17 NHC-CO2 derivatives.
      Computed bond distances and angles have been compared with experimental data.

PMID- 28510436
TI  - Direct Observations of Graphene Dispersed in Solution by Twilight Fluorescence
      Microscopy.
AB  - Graphene and graphene oxide (GO) in solution were directly observed by a newly
      developed twilight fluorescence (TwiF) microscopy. A nanocarbon dispersion was
      mixed with a highly concentrated fluorescent dye solution and placed in a cell
      with a viewing glass at the bottom. TwiF microscopy images the nanocarbon
      material floating within a few hundred MUm of the glass surface by utilizing two
      optical processes to provide a faintly illuminating backlight and visualizes GO
      as either a dark image by absorption and energy transfer processes or a bright
      image by alternation of fluorophore chemistry and autofluorescence. Individual
      graphene and GO sheets ranging from submicron to submillimeter widths were
      clearly imaged at different wavelengths, which were selectable based on the dye
      used. Graphene could be differentiated from GO coexisting in the same solution.
      Partial transparency revealed layering and network structures. Motions in
      tumbling flow were recognized in real time. An effect of changing the solvent and
      the process of adhesion on the glass surface were followed in situ.

PMID- 28510437
TI  - Spline Based Shape Prediction and Analysis of Uniformly Rotating Sessile and
      Pendant Droplets.
AB  - Prediction and analysis of the shapes of liquid-vapor interface of droplets under
      the influence of external forces is critical for various applications. In this
      regard, a geometric model that can capture the macroscopic shape of the liquid
      vapor interface in tandem with the subtleties near the contact line, particularly
      in the regime where the droplet shape deviates significantly from the idealized
      spherical cap geometry, is desirable. Such deviations may occur when external
      forces such as gravity or centrifugal dominate over the surface tension force.
      Here we use vector parametrized cubic spline representation for axisymmetric
      fluid-fluid interfaces along with a novel thermodynamic free energy minimization
      based heuristic to determine the shape of liquid-vapor interface of droplets. We
      show that the current scheme can easily predict the shapes of sessile and pendant
      droplets under the action of centrifugal force over a broad range of surface
      contact angle values and droplet sizes encountered in practical applications.
      Finally, we show that the cubic spline based modeling approach makes it
      convenient to perform the inverse analysis as well, i.e., predict interfacial
      properties from the shape of a droplet under the action of various types of
      external forces including gravity and centrifugal. We believe that this versatile
      modeling approach can be extended to model droplet shapes under various other
      external forces including electric and acoustic. In addition, the simple shape
      analysis approach is also promising for the development of inexpensive
      interfacial analysis tools such as surface tensiometers.

PMID- 28510438
TI  - Complex Effects of 24:1 Sphingolipids in Membranes Containing
      Dioleoylphosphatidylcholine and Cholesterol.
AB  - The effects of C24:1 sphingolipids have been tested in phospholipid bilayers
      containing cholesterol. Confocal microscopy, differential scanning calorimetry,
      and atomic force microscopy imaging and force curves have been used. More
      precisely, the effects of C24:1 ceramide (nervonoyl ceramide, nCer) were
      evaluated and compared to those of C16:0 ceramide (palmitoyl ceramide, pCer) in
      bilayers composed basically of dioleoylphosphatidylcholine, sphingomyelin (either
      C24:1, nSM or C16:0, pSM) and cholesterol. Combination of equimolecular amounts
      of C24:1 and C16:0 sphingolipids were also studied under the same conditions.
      Results show that both pCer and nCer are capable of forming segregated gel
      domains. Force spectroscopy data point to nCer having a lower stiffening effect
      than pCer, while the presence of nSM reduces the stiffness. DSC reveals Tm
      reduction by nSM in every case. Furthermore, pSM seems to better accommodate both
      ceramides in a single phase of intermediate properties, while nSM partial
      accommodation of ceramides generates different gel phases with higher stiffnesses
      caused by interceramide cooperation. If both pSM and nSM are present, a clear
      preference of both ceramides toward pSM is observed. These findings show the
      sharp increase in complexity when membranes exhibit different sphingolipids of
      varying N-acyl chains, which should be a common issue in an actual cell membrane
      environment.

PMID- 28510439
TI  - Characterization of the Isothermal Compression Behavior of LLM-172.
AB  - The high-pressure behavior of 3,4-bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5
      oxadiazole (LLM-172) has been studied to 36 GPa by Raman spectroscopy and 50 GPa
      by X-ray diffraction. The Raman spectra and calculated unit-cell volumes at
      select pressures show reasonable qualitative agreement with first-principles
      density functional theory calculations. Raman peaks exhibit a gradual broadening
      and loss of intensity upon compression to near 20 GPa. Above 20 GPa, most Raman
      features disappear with the exception of modes associated with the skeletal ring
      modes. These modes were found to persist (although with low intensity) to 36 GPa.
      Because these modes exhibit very low compressibility over the pressure range
      studied, it is speculated that the ring structure is very stable. The X-ray
      diffraction suggests that while the crystal maintains an orthorhombic structure
      to near 40 GPa, it gradually undergoes a decomposition/amorphization beginning
      near 10 GPa. Analysis of the Raman results suggests that decomposition proceeds
      through isomerization, which leads to the formation of a C-O-N-O group rather
      than ring cleavage.

PMID- 28510440
TI  - Fundamental Characterization of the Micellar Self-Assembly of Sophorolipid
      Esters.
AB  - Surfactants are ubiquitous constituents of commercial and biological systems that
      function based on complex structure-dependent interactions. Sophorolipid (SL) n
      alkyl esters (SL-esters) comprise a group of modified naturally derived
      glycolipids from Candida bombicola. Herein, micellar self-assembly behavior as a
      function of SL-ester chain length was studied. Surface tensions as low as 31.2
      mN/m and critical micelle concentrations (CMCs) as low as 1.1 MUM were attained
      for diacetylated SL-decyl ester (dASL-DE) and SL-octyl ester, respectively. For
      deacetylated SL-esters, CMC values reach a lower limit at SL-ester chains above n
      butyl (SL-BE, 1-3 MUM). This behavior of SL-esters with increasing hydrophobic
      tail length is unlike other known surfactants. Diffusion-ordered spectroscopy
      (DOSY) and T1 relaxation NMR experiments indicate this behavior is due to a
      change in intramolecular interactions, which impedes the self-assembly of SL
      esters with chain lengths above SL-BE. This hypothesis is supported by micellar
      thermodynamics where a disruption in trends occurs at n-alkyl ester chain lengths
      above those of SL-BE and SL-hexyl ester (SL-HE). Diacetylated (dA) SL-esters
      exhibit an even more unusual trend in that CMC increases from 1.75 to 815 MUM for
      SL-ester chain lengths of dASL-BE and dASL-DE, respectively. Foaming studies,
      performed to reveal the macroscopic implications of SL-ester micellar behavior,
      show that the observed instability in foams formed using SL-esters are due to
      coalescence, which highlights the importance of understanding intermicellar
      interactions. This work reveals that SL-esters are an important new family of
      green high-performing surfactants with unique structure-property relationships
      that can be tuned to optimize micellar characteristics.

PMID- 28510442
TI  - Free Energy Landscape of Cellulose as a Driving Factor in the Mobility of
      Adsorbed Water.
AB  - The diffusion coefficient of water adsorbed in hydrophilic porous materials, such
      as noncrystalline cellulose, depends on water activity. Faster diffusion at
      higher water concentrations is observed in experimental and modeling studies. In
      this paper, two asymptotic water concentrations, near-vacuum and fully saturated,
      are investigated at the surface of crystalline cellulose with molecular dynamics
      simulations. An increasing water concentration leads to significant changes in
      the free energy landscape due to perturbation of local electrostatic potential.
      Smoothening of strong energy minima, corresponding to sorption sites, and
      formation of layered structure facilitates water transport in the vicinity of
      cellulose. The determined transition probabilities and hydrogen bond stability
      reflect the changes in the energy landscape. As a result of a concentration
      increase, the emerging basins of attraction and spreading out of those existing
      in the diluted state lead to an increase in water entropy. Thermal fluctuations
      of cellulose are demonstrated to rearrange the landscape in the diluted limit,
      increase adsorbed water entropy, and decrease the water-cellulose H-bond
      lifetime.

PMID- 28510441
TI  - Molybdenum Carbamate Nanosheets as a New Class of Potential Phase Change
      Materials.
AB  - We report for the first time the synthesis of large, free-standing, Mo2O2(MU
      S)2(Et2dtc)2 (MoDTC) nanosheets (NSs), which exhibit an electron-beam induced
      crystalline-to-amorphous phase transition. Both electron beam ionization and
      femtosecond (fs) optical excitation induce the phase transition, which is size-,
      morphology-, and composition-preserving. Resulting NSs are the largest, free
      standing regularly shaped two-dimensional amorphous nanostructures made to date.
      More importantly, amorphization is accompanied by dramatic changes to the NS
      electrical and optical response wherein resulting amorphous species exhibit room
      temperature conductivities 5 orders of magnitude larger than those of their
      crystalline counterparts. This enhancement likely stems from the amorphization
      induced formation of sulfur vacancy-related defects and is supported by
      temperature-dependent transport measurements, which reveal efficient variable
      range hopping. MoDTC NSs represent one instance of a broader class of transition
      metal carbamates likely having applications because of their intriguing
      electrical properties as well as demonstrated ability to toggle metal oxidation
      states.

PMID- 28510443
TI  - Light-Controlled Switching of a Non-photoresponsive Molecular Shuttle.
AB  - In this research, we report that the acid/base-switchable molecular shuttle
      without any photoresponsive group can be controlled photochemically by coupling
      to the indazole-based photoacid via an intermolecular proton-transfer process.
      The photocontrolled shuttling of the wheel can be conveniently monitored by
      following the fluorescent evolution during the photoirradiation.

PMID- 28510445
TI  - Establishment of a Direct-Injection Electron Ionization-Mass Spectrometry
      Metabolomics Method and Its Application to Lichen Profiling.
AB  - Direct-injection electron ionization-mass spectrometry (DI-EI-MS) is a
      multivariate analysis method useful for characterizing biological materials. We
      demonstrated the use of DI-EI-MS for metabolic profiling using several closely
      related lichen species: Cladonia krempelhuberi, C. gracilis, C. pseudogymnopoda,
      and C. ramulosa. The methodology involves conversion of total ion chromatograms
      to integrated chromatograms and assessment of reproducibility. The qualitative DI
      EI-MS method was used to profile the major and/or minor constituents in extracts
      of lichen samples. It was possible to distinguish each lichen sample by altering
      the electron energy in DI-EI-MS and examining the resulting data using one-way
      analysis of variance. Previously undetectable peaks, which are easy to fragment
      could be revealed by varying the electron energy. Our results suggest that
      metabolic profiling using DI-EI-MS would be useful for discriminating between
      subgroups within the same species. This is the first study to report the use of
      DI-EI-MS in a metabolomics application.

PMID- 28510444
TI  - Acetic Acid Promoted Redox Annulations with Dual C-H Functionalization.
AB  - Amines such as 1,2,3,4-tetrahydroisoquinoline undergo redox-neutral annulations
      with 2-alkylquinoline-3-carbaldehydes as well as the corresponding 4-alkyl
      isomers and pyridine analogues. These processes involve dual C-H bond
      functionalization. Acetic acid is used as a cosolvent and acts as the sole
      promoter of these transformations.

PMID- 28510447
TI  - Synthesis of a Highly Azide-Reactive and Thermosensitive Biofunctional Reagent
      for Efficient Enrichment and Large-Scale Identification of O-GlcNAc Proteins by
      Mass Spectrometry.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational
      modification of proteins in eukaryotic cells. Despite their low abundance, O
      GlcNAc-modified proteins play many important roles in regulating gene expression,
      signal transduction, and cell cycle. Aberrant O-GlcNAc proteins are correlated
      with many major human diseases, such as Alzheimer's disease, diabetes, and
      cancer. Because of the extremely low stoichiometry of O-GlcNAc proteins,
      enrichment is required before mass spectrometry analysis for large-scale
      identification and in-depth understanding of their cellular function. In this
      work, we designed and synthesized a novel thermosensitive immobilized
      triarylphosphine reagent as a convenient tool for efficient enrichment of azide
      labeled O-GlcNAc proteins from complex biological samples. Immobilization of
      triarylphosphine on highly water-soluble thermosensitive polymer largely
      increases its solubility and reactivity in aqueous solution. As a result,
      facilitated coupling is achieved between triarylphosphine and azide-labeled O
      GlcNAc proteins via Staudinger ligation, due to the increased triarylphosphine
      concentration, reduced interfacial mass transfer resistance, and steric hindrance
      in homogeneous reaction. Furthermore, solubility of the polymer from complete
      dissolution to full precipitation can be easily controlled by simply adjusting
      the environmental temperature. Therefore, facile sample recovery can be achieved
      by increasing the temperature to precipitate the polymer-O-GlcNAc protein
      conjugates from solution. This novel immobilized triarylphosphine reagent enables
      efficient enrichment and sensitive detection of more than 1700 potential O-GlcNAc
      proteins from HeLa cell using mass spectrometry, demonstrating its potential as a
      general strategy for low-abundance target enrichment.

PMID- 28510446
TI  - Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of
      Intracellular Proteases for Targeted Cytotoxicity.
AB  - Targeted therapies promise to increase the safety and efficacy of treatments
      against diseases ranging from cancer to viral infections. However, the vast
      majority of targeted therapeutics relies on the recognition of extracellular
      biomarkers, which are rarely restricted to diseased cells and are thus prone to
      severe and sometimes-fatal off-target toxicities. In contrast, intracellular
      antigens present a diverse yet underutilized repertoire of disease markers. Here,
      we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein
      VErifier and Response Trigger (COVERT)-which enables the interrogation of
      intracellular proteases to trigger targeted cytotoxicity. COVERT molecules
      consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N
      terminal peptide, which can be removed by researcher-specified proteases to
      activate GrB function. We demonstrate that fusion of a small ubiquitin-like
      modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically
      activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB
      selectively triggers apoptotic phenotypes in HEK293T cells that overexpress
      SENP1, and it is highly sensitive to different SENP1 levels across cell lines. We
      further demonstrate the rational design of additional COVERT molecules responsive
      to enterokinase (EK) and tobacco etch virus protease (TEVp), highlighting the
      COVERT platform's modularity and adaptability to diverse protease targets. As an
      initial step toward engineering COVERT-T cells for adoptive T-cell therapy, we
      verified that primary human T cells can express, package, traffic, and deliver
      engineered GrB molecules in response to antigen stimulation. Our findings set the
      foundation for future intracellular-antigen-responsive therapeutics that can
      complement surface-targeted therapies.

PMID- 28510448
TI  - Oxidized or Reduced Cytochrome c and Axial Ligand Variants All Form the
      Apoptosome in Vitro.
AB  - Cytochrome c (cyt c) has two important roles in vertebrates: mitochondrial
      electron transport and activating the intrinsic cell death pathway (apoptosis).
      To initiate cell death, cyt c dissociates from the inner mitochondrial membrane
      and migrates to the cytosol. In the cytosol, cyt c interacts stoichiometrically
      with apoptotic protease activating factor 1 (Apaf-1) and upon ATP binding induces
      formation of the heptameric apoptosome. It is not clear however what the redox
      state of cyt c is when it functions as the "active signal" for apoptosis. Some
      reports have indicated that only ferri (i.e., oxidized Fe3+ heme) but not ferro
      (reduced, Fe2+ heme) cyt c forms the apoptosome. Facilitated by our recently
      described recombinant system for synthesizing novel human cyt c proteins, we use
      a panel of cyt c axial ligand variants that exhibit a broad range of redox
      potentials. These variants exist in different redox states. Here we show that cyt
      c wild type and cyt c H19M (reduced state) and cyt c M81A and cyt c M81H
      (oxidized state) all bind to Apaf-1 and form the apoptosome.

PMID- 28510450
TI  - Enhancement of Antioxidative and Intestinal Anti-inflammatory Activities of
      Glycated Milk Casein after Fermentation with Lactobacillus rhamnosus 4B15.
AB  - In this study, we investigated the glycoproteomics of glycated milk casein (GMC)
      and GMC fermented by Lactobacillus rhamnosus 4B15 (FGMC) and determined their
      biological implications. There was a significant increase in the antioxidative
      and anti-inflammatory activities of GMC with galactose, which were higher than
      those of GMC with glucose (GMC-glc). Furthermore, the fermentation of GMC by L.
      rhamnosus 4B15 synergistically enhanced the above activities compared to those of
      unfermented GMC. Especially, fermented GMC-glc (FGMC-glc) possessed remarkably
      improved reducing power and radical scavenging activities. Moreover, FGMC-glc
      ameliorated the inflammatory response and tight junction-related intestinal
      epithelial dysfunction. Additionally, hexose-derived glycation and modification
      sites in protein sequences of GMC were identified. In particular, glycosylation
      and sulfation of serine and threonine residues were observed, and distinct
      modification sites were detected after fermentation. Therefore, these results
      indicated that glycation-induced modification of casein and fermentation
      correlated strongly with the enhanced functional properties.

PMID- 28510449
TI  - Scalable, Electrochemical Oxidation of Unactivated C-H Bonds.
AB  - A practical electrochemical oxidation of unactivated C-H bonds is presented. This
      reaction utilizes a simple redox mediator, quinuclidine, with inexpensive carbon
      and nickel electrodes to selectively functionalize "deep-seated" methylene and
      methine moieties. The process exhibits a broad scope and good functional group
      compatibility. The scalability, as illustrated by a 50 g scale oxidation of
      sclareolide, bodes well for immediate and widespread adoption.

PMID- 28510451
TI  - Mechanisms and Origins of Selectivities of the Lewis Acid-Catalyzed Diels-Alder
      Reactions between Arylallenes and Acrylates.
AB  - The mechanisms of recently reported Lewis acid-catalyzed Diels-Alder reactions of
      arylallenes and acrylates were studied using density functional theory
      calculations. A stepwise mechanism involving short-lived zwitterion intermediates
      is established. The reaction is endo-selective in the presence of Lewis acid
      catalyst. The [2 + 2] cycloaddition is not observed because of the greater charge
      separation in the first step of the [2 + 2] cycloaddition. The origins of
      chirality transfer in the Diels-Alder reaction using chiral arylallenes are
      uncovered, and the absolute stereochemistry of the product is predicted.

PMID- 28510453
TI  - Influence of Local Heating on Marangoni Flows and Evaporation Kinetics of Pure
      Water Drops.
AB  - The effect of localized heating on the evaporation of pure sessile water drops
      was probed experimentally by a combination of infrared thermography and optical
      imaging. In particular, we studied the effect of three different heating powers
      and two different locations, directly below the center and edge of the drop. In
      all cases, four distinct stages were identified according to the emerging thermal
      patterns. In particular, depending on heating location, recirculating vortices
      emerge that either remain pinned or move azimuthally within the drop. Eventually,
      these vortices oscillate in different modes depending on heating location.
      Infrared data allowed extraction of temperature distribution on each drop
      surface. In turn, the flow velocity in each case was calculated and was found to
      be higher for edge heating, due to the one-directional nature of the heating.
      Additionally, calculation of the dimensionless Marangoni and Rayleigh numbers
      yielded the prevalence of Marangoni convection. Heating the water drops also
      affected the evaporation kinetics by promoting the "stick-slip" regime. Moreover,
      both the total number of depinning events and the pinning strength were found to
      be highly dependent on heating location. Lastly, we report a higher than
      predicted relationship between evaporation rate and heating temperature, due to
      the added influence of the recirculating flows on temperature distribution and
      hence evaporation flux.

PMID- 28510452
TI  - Rational Optimization of Mechanism-Based Inhibitors through Determination of the
      Microscopic Rate Constants of Inactivation.
AB  - Mechanism-based inhibitors (MBIs) are widely employed in chemistry, biology, and
      medicine because of their exquisite specificity and sustained duration of
      inhibition. Optimization of MBIs is complicated because of time-dependent
      inhibition resulting from multistep inactivation mechanisms. The global kinetic
      parameters kinact and KI have been used to characterize MBIs, but they provide
      far less information than is commonly assumed, as shown by derivation and
      simulation of these parameters. We illustrate an alternative and more rigorous
      approach for MBI characterization through determination of the individual
      microscopic rate constants. Kinetic analysis revealed the rate-limiting step of
      inactivation of the PLP-dependent enzyme BioA by dihydro-(1,4)-pyridone 1. This
      knowledge was subsequently applied to rationally design a second-generation
      inhibitor scaffold with a nearly optimal maximum inactivation rate (0.48 min-1).

PMID- 28510454
TI  - Kinetic Mechanism of Thioflavin T Binding onto the Amyloid Fibril of Hen Egg
      White Lysozyme.
AB  - Thioflavin T (ThT) is widely used as a fluorescent probe for amyloid fibril
      detection. Yet the exact kinetic mechanism of ThT binding onto amyloid fibril
      remains elusive. Previously reported kinetic studies using ThT-fluorescence
      detected kinetic design suggested two completely different ThT-binding
      mechanisms. In one study, a multistep sequential binding mechanism onto a single
      ThT-binding site was suggested. In another study, a one-step parallel binding
      mechanism onto multiple ThT-binding sites was suggested. The discrepancy is
      likely due to the incapability of ThT-fluorescence-detected kinetic design to
      differentiate the two above-mentioned mechanisms. Considering the weakness of the
      ThT-fluorescence-detected approach, we investigated the ThT-binding mechanism
      onto the amyloid fibril of hen egg white lysozyme (HEWL) using a new approach,
      ThT-absorbance-detected kinetic design. Our new results suggest that ThT binds to
      HEWL fibril through the one-step parallel binding mechanism. We hope our work can
      offer some new insights into the interactions between dye molecules and amyloid
      fibrils.

PMID- 28510455
TI  - Clinically Relevant Multidrug Transporters Are Regulated by microRNAs along the
      Human Intestine.
AB  - Intestinal drug transporters are crucial determinants for absorption and oral
      bioavailability of drugs. In healthy tissue donors, a recent study revealed
      profound discrepancies between mRNA expression and protein abundance as well as
      differences in the protein content between small and large intestine for
      clinically relevant multidrug transporters as the ATP binding cassette
      transporter subfamily B member 1 (ABCB1) and subfamily C member 3 (ABCC3) and the
      solute carrier family 15 member 1 (SLC15A1, PEPT1). As the mechanisms underlying
      these observations remained unclear, the aim of the present study was to
      elucidate the intestinal regiospecific microRNA profile under physiological
      conditions and identify specific microRNAs contributing to the post
      transcriptional regulation of major drug transporters. For this purpose, tissue
      samples were collected from six intestinal sites obtained from six healthy tissue
      donors. The expression of 754 microRNAs was determined using qRT-PCR based low
      density arrays, and microRNA expression levels were correlated with transporter
      protein abundance quantified by targeted proteomics. A total of 241 microRNA
      transporter pairs were identified, showing significant negative correlations to
      protein abundance (p < 0.05). Out of these, for nine pairs, the binding of the
      microRNA to the respective transporter 3'-UTR was predicted in silico. Besides
      the already known interactions of miR-27a-3p-ABCB1 and miR-193a-3p-PEPT1,
      reporter gene assays confirmed binding of miR-192-5p to the ABCC3 3'-UTR
      (reduction of reporter gene activity by 31%; p = 0.0012), miR-409-3p to the ABCB1
      3'-UTR (reduction by 38%; p = 0.0006), and miR-193b-3p as well as miR-27a-3p to
      PEPT1 3'-UTR (reduction by 49% (p = 0.0012) and 20% (p = 0.0043), respectively).
      These results suggest that mucosal microRNA expression contributes to the
      explanation of discrepancies between mRNA expression and protein abundance as
      well as site-dependent differences in protein content along the human intestine
      under physiological conditions, as exemplified for ABCB1, ABCC3, and PEPT1.

PMID- 28510456
TI  - Thermoresponsive Pickering Emulsions Stabilized by Silica Nanoparticles in
      Combination with Alkyl Polyoxyethylene Ether Nonionic Surfactant.
AB  - We put forward a simple protocol to prepare thermoresponsive Pickering emulsions.
      Using hydrophilic silica nanoparticles in combination with a low concentration of
      alkyl polyoxyethylene monododecyl ether (C12En) nonionic surfactant as
      emulsifier, oil-in-water (o/w) emulsions can be obtained, which are stable at
      room temperature but demulsified at elevated temperature. The stabilization can
      be restored once the separated mixture is cooled and rehomogenized, and this
      stabilization-destabilization behavior can be cycled many times. It is found that
      the adsorption of nonionic surfactant at the silica nanoparticle-water interface
      via hydrogen bonding between the oxygen atoms in the polyoxyethylene headgroup
      and the SiOH groups on particle surfaces at low temperature is responsible for
      the in situ hydrophobization of the particles rendering them surface-active.
      Dehydrophobization can be achieved at elevated temperature due to weakening or
      loss of this hydrogen bonding. The time required for demulsification decreases
      with increasing temperature, and the temperature interval between stabilization
      and destabilization of the emulsions is affected by the surfactant headgroup
      length. Experimental evidence including microscopy, adsorption isotherms, and
      three-phase contact angles is provided to support the mechanism.

PMID- 28510457
TI  - Spatiotemporal Evolution of Coherent Elastic Strain Waves in a Single MoS2 Flake.
AB  - We use bright-field imaging in an ultrafast electron microscope to
      spatiotemporally map the evolution of photoexcited coherent strain waves in a
      single, micrometer-size flake of MoS2. Following in situ femtosecond
      photoexcitation, we observe individual wave trains emerge from discrete nanoscale
      morphological features and propagate in-plane along specific wave vectors at
      approximately the speed of sound (7 nm/ps). Over the span of several hundred
      picoseconds, the 50 GHz wave trains (20 ps periods) are observed to undergo
      phonon-phonon scattering and wave-train interference, resulting in a transition
      to larger-scale, incoherent structural dynamics. This incoherent motion further
      evolves into coherent nanomechanical oscillations over a few nanoseconds,
      ultimately leading to megahertz, whole-flake multimode resonances having
      microsecond lifetimes. These results provide insight into the low-frequency
      structural response of MoS2 to relatively coherent optical photoexcitation by
      elucidating the origin and the evolution of high-velocity, gigahertz strain
      waves.

PMID- 28510459
TI  - Efficient Round-Trip Time Optimization for Replica-Exchange Enveloping
      Distribution Sampling (RE-EDS).
AB  - Replica-exchange enveloping distribution sampling (RE-EDS) allows the efficient
      estimation of free-energy differences between multiple end-states from a single
      molecular dynamics (MD) simulation. In EDS, a reference state is sampled, which
      can be tuned by two types of parameters, i.e., smoothness parameters(s) and
      energy offsets, such that all end-states are sufficiently sampled. However, the
      choice of these parameters is not trivial. Replica exchange (RE) or parallel
      tempering is a widely applied technique to enhance sampling. By combining EDS
      with the RE technique, the parameter choice problem could be simplified and the
      challenge shifted toward an optimal distribution of the replicas in the
      smoothness-parameter space. The choice of a certain replica distribution can
      alter the sampling efficiency significantly. In this work, global round-trip time
      optimization (GRTO) algorithms are tested for the use in RE-EDS simulations. In
      addition, a local round-trip time optimization (LRTO) algorithm is proposed for
      systems with slowly adapting environments, where a reliable estimate for the
      round-trip time is challenging to obtain. The optimization algorithms were
      applied to RE-EDS simulations of a system of nine small-molecule inhibitors of
      phenylethanolamine N-methyltransferase (PNMT). The energy offsets were determined
      using our recently proposed parallel energy-offset (PEOE) estimation scheme.
      While the multistate GRTO algorithm yielded the best replica distribution for the
      ligands in water, the multistate LRTO algorithm was found to be the method of
      choice for the ligands in complex with PNMT. With this, the 36 alchemical free
      energy differences between the nine ligands were calculated successfully from a
      single RE-EDS simulation 10 ns in length. Thus, RE-EDS presents an efficient
      method for the estimation of relative binding free energies.

PMID- 28510458
TI  - Interplay between Hydrogen Bonding and Vibrational Coupling in Liquid N
      Methylacetamide.
AB  - Intrinsically disordered proteins play an important role in biology, and
      unraveling their labile structure presents a vital challenge. However, the
      dynamical structure of such proteins thwarts their study by standard techniques
      such as X-ray diffraction and NMR spectroscopy. Here, we use a neat liquid
      composed of N-methylacetamide molecules as a model system to elucidate dynamical
      and structural properties similar to those one can expect to see in intrinsically
      disordered proteins. To examine the structural dynamics in the neat liquid, we
      combine molecular dynamics, response-function-based spectral simulations, and two
      dimensional polarization-resolved infrared spectroscopy in the amide I (CO
      stretch) region. The two-dimensional spectra reveal a delicate interplay between
      hydrogen bonding and intermolecular vibrational coupling effects, observed
      through a fast anisotropy decay. The present study constitutes a general platform
      for understanding the structure and dynamics of highly disordered proteins.

PMID- 28510460
TI  - Effects of Membrane Defects and Polymer Hydrophobicity on Networking Kinetics of
      Vesicles.
AB  - The kinetics of clustering unilamellar vesicles induced by inverse Pluronics
      [poly(propylene oxide)m-poly(ethylene oxide)n-poly(propylene oxide)m, POm-EOn
      POm] was investigated via experiments and molecular dynamic simulations. Two
      important factors for controlling the networking kinetics are the membrane
      defects, presumably located at the interfacial region between two lipid domains
      induced by acyl chain mismatch, and the polymer hydrophobicity. As expected, the
      clustering rate increases significantly with increasing bilayer defects on the
      membrane where the insertion of PPO is likely to take place because of the
      reduced energy barrier for the insertion of PO. The hydrophobic interaction
      between the PO blocks and membranes with the defects region dictates the
      "anchoring" kinetics, which is controlled by the association-dissociation of PO
      with the lipid membrane. As a result, the dependence of clustering rate on
      polymer concentration is strongly influenced by the hydrophobicity of the PO
      blocks. Nevertheless, longer PO blocks show stronger association with the
      membrane, resulting in faster consumption of the "active" sites made of these
      defect regions (causing mostly "invalid" insertions) with increasing polymer
      concentration, hence inhibiting the formation of large networking clusters, while
      shorter PO blocks undergo more frequent association with/dissociation from the
      defects, allowing continuous formation of larger clusters with increasing polymer
      concentration. This study provides important insights into how the organization
      and dynamics of a biomembrane influence its interaction with foreign amphiphilic
      molecules.

PMID- 28510461
TI  - Underlying Causes of Persistent and Recurrent Pneumonia in Children at a
      Pulmonary Referral Hospital in Tehran, Iran.
AB  - BACKGROUND: There is limited data on recurrent or persistent pneumonia in
      children, particularly in the developing world. This is a retrospective, cross
      sectional study of children with recurrent or persistent pneumonia admitted to
      the Pediatric Department of Massih Daneshvari Hospital, Tehran, Iran. METHODS:
      Children under 18 years of age, who were admitted to the hospital with pneumonia
      between 2007 and 2013, were investigated to find out the prevalence of recurrent
      and persistent pneumonia and to recognize their underlying diseases. Descriptive
      statistics were calculated for all data. RESULTS: Out of 601 children admitted
      for pneumonia, 229 (38.1%) met the criteria for recurrent or persistent
      pneumonia. An underlying illness was identified in 194 patients (84.72%). The
      most common underlying causes of recurrent pneumonia included aspiration syndrome
      (51.75%), recurrent wheezing (20.17%), and congenital heart diseases (20.17%).
      The most common underlying illness of persistent pneumonia included pulmonary
      tuberculosis (38.75%), recurrent wheezing (28.75%), and aspiration syndrome
      (26.25%). CONCLUSIONS: The result showed that the majority of patients with
      recurrent or persistent pneumonia had an underlying illness. New strategies and
      guidelines are required for early diagnosis of underlying causes of recurrent or
      persistent pneumonia in children.

PMID- 28510462
TI  - Anti-Plasmodial Assessment of Four Different Iranian Propolis Extracts.
AB  - BACKGROUND: Eradication of malaria will depend on discovery of new intervention
      tools such as anti-malarial drugs. Due to the increasing interest in the
      application of propolis against significant clinical pathogenic agents, the aim
      of the present investigation was to evaluate the anti-plasmodial effect of
      Iranian propolis extracts against chloroquine (CQ)-sensitive Plasmodium
      falciparum 3D7 and Plasmodium berghei (ANKA strain). METHODS: Crude samples of
      honeybee (Apis mellifera) propolis were collected from four provinces in northern
      (Kalaleh, Golestan), northeastern (Chenaran, Razavi Khorasan), central (Taleghan,
      Alborz) and western (Morad Beyg, Hamedan) areas of Iran with different types of
      flora. The dried propolis samples were extracted with three different solvents,
      including ethanol 70% (EtOH), ethyl acetate (EA) and dichloromethane (DCM).
      RESULTS: All extracts were shown to have in vitro anti-plasmodial activity with
      IC50 ranging from 16.263 to 80.012 ug/mL using parasite lactate dehydrogenase
      (pLDH) assay. The DCM extract of Morad Beyg propolis indicated the highest anti
      plasmodial activity (IC50: 16.263 +/- 2.910 MUg/mL; P = 0.027, Kruskal-Wallis H
      test). The samples were also evaluated in mice for their in vivo anti-plasmodial
      effect. The curative effect against established infection (Rane test) showed that
      both extracts at all doses (50, 100, and 200 mg/kgBW) produced anti-plasmodial
      activity against the parasite. Furthermore, using gas chromatography-mass
      spectrometry (GC-MS), the quantity of flavonoids in DCM and EtOH 70% extracts
      were found to be 7.42% and 3.10%, respectively. CONCLUSION: The potent anti
      plasmodial activity of both EtOH 70% and DCM extracts of the propolis of Morad
      Beyg, Hamedan suggests further analyses of individual components to assess its
      utilization as anti-malarial drugs.

PMID- 28510463
TI  - Factors Associated with Incidence of Induced Abortion in Hamedan, Iran.
AB  - BACKGROUND: There is limited reliable information on abortion in Iran, where
      abortion is illegal and many women of reproductive age seek clandestine abortion
      to end their unintended pregnancy. This study aims to examine the determinants of
      induced abortion in the city of Hamedan, Iran. METHODS: The study utilizes recent
      data from the 2015 Hamedan Survey of Fertility, conducted in a representative
      sample of 3,000 married women aged 15-49 years in the city of Hamedan, Iran.
      Binary logistic regression models are used to examine factors associated with the
      incidence of abortion. RESULTS: Overall, 3.8% of respondents reported having had
      an induced abortion in their life. Multivariate results showed that the incidence
      of abortion was strongly associated with women's education, type of contraceptive
      and family income level, after controlling for confounding factors. Women using
      long-acting contraceptive methods, those educated under high school diploma or
      postsecondary education, and those with high level of income were more likely to
      report having an induced abortion. CONCLUSION: The high incidence of abortion
      among less or more educated women and those with high income level signifies
      unmet family planning needs among these women, which must be addressed by focused
      reproductive health and family planning programs.

PMID- 28510464
TI  - A Stakeholder Perspective on Diabetes Mellitus and Diabetic Retinopathy Care in
      Iran; A Qualitative Study.
AB  - OBJECTIVE: To assess the national health system for management of diabetes
      mellitus (DM) in Iran, with particular focus on diabetic retinopathy (DR).
      MATERIALS AND METHODS: In this qualitative study, the national stakeholders
      related to DR and DM management system were invited to participate. Two
      researchers performed interview using a semi-structured questionnaire recommended
      by the World Health Organization titled "Tool for Assessment of Diabetic
      Retinopathy and DM Management Systems". The questionnaire contains seven
      different sections, each consisting of closed and open-ended questions, and a
      final Likert-type score, ranging from 1 indicating the worst to 4 indicating the
      best status. Inconsistencies were resolved through a collective decision of the
      research team, followed by a focus group discussion with stakeholders at the
      Ministry of Health. RESULTS: Fourteen stakeholders out of 15 total invitees were
      interviewed (response rate: 93.3%). There were national priorities, defined
      policies, and running programs (score = 3), but the care system should be
      strengthened in terms of implementation of clinical guidelines, with specific
      reference to the availability of regular screenings for DR (score = 2). The
      network of care providers, health information systems, and promotional programs
      were insufficient (score = 2). The health workforce and technology for DR and DM
      were acceptable (scores 4 and 3, respectively); however, there were concerns
      about the appropriate distribution and utilization of resources and out-of-pocket
      costs paid by patients. CONCLUSION: The existence of national policies, programs,
      a qualified workforce, and modern technology is promising. Nevertheless, other
      aspects of the health system need to be improved to ensure access to health and
      eye care for people with DM and achieve universal health coverage.

PMID- 28510465
TI  - Cigarette and Water-Pipe Use in Iran: Geographical Distribution and Time Trends
      among the Adult Population; A Pooled Analysis of National STEPS Surveys, 2006
      2009.
AB  - OBJECTIVE: To assess the geographical distribution and time trends of
      manufactured cigarette and water-pipe use among Iranian adult population. METHOD:
      Pooled data from four consecutive nationally and provincially representative
      STEPS surveys, 2006-2009, were analyzed. Prevalence of current daily manufactured
      cigarette smokers, current daily water-pipe and current daily dual users and
      associated 95%CIs were estimated using complex sample analysis techniques.
      RESULTS: Overall, the prevalence of current daily tobacco use, including
      cigarette and water-pipe, was estimated 23.7% for men and 3.0% for women, in
      which 20.2% of men and 0.8% of women were exclusively cigarette smokers, 2.7% and
      2.2% were exclusively water-pipe users, and 0.6% and 0.01% smoked both cigarettes
      and water-pipes. The prevalence of cigarette smoking ranged from 12.3% to 27.7%
      in men and 0.1% to 1.8% in women, and was generally highest in the northwest of
      the country. Conversely, the prevalence of water-pipe smoking ranged from 1.7% to
      10.9% in men and 0% to 16.8% in women, and was highest in the south and
      southeast. No secular trends were observed for daily cigarette smoking in either
      men (P = 0.637) or women (P = 0.308) from 2006 to 2009. However, the prevalence
      of water-pipe decreased slightly in women (P = 0.012) and men (P = 0.055), though
      the later was not statistically significant. CONCLUSION: In Iran, widespread
      geographical variation in the use of different types of tobacco products should
      be taken into account when planning for tobacco prevention policies and programs.
      Iran may serve as an important setting for etiological studies to examine the
      effects of long-term water pipe use on diseases.

PMID- 28510466
TI  - Empirical Bayesian Geographical Mapping of Occupational Accidents among Iranian
      Workers.
AB  - BACKGROUND: Work-related accidents are believed to be a serious preventable cause
      of mortality and disability worldwide. This study aimed to provide Bayesian
      geographical maps of occupational injury rates among workers insured by the
      Iranian Social Security Organization. METHODS: The participants included all
      insured workers in the Iranian Social Security Organization database in 2012. One
      of the applications of the Bayesian approach called the Poisson-Gamma model was
      applied to estimate the relative risk of occupational accidents. Data analysis
      and mapping were performed using R 3.0.3, Open-Bugs 3.2.3 rev 1012 and ArcMap9.3.
      RESULTS: The majority of all 21,484 investigated occupational injury victims were
      male (98.3%) including 16,443 (76.5%) single workers aged 20 - 29 years. The
      accidents were more frequent in basic metal, electric, and non-electric machining
      jobs. About 0.4% (96) of work-related accidents led to death, 2.2% (457) led to
      disability (partial and total), 4.6% (980) led to fixed compensation, and 92.8%
      (19,951) of the injured victims recovered completely. The geographical maps of
      estimated relative risk of occupational accidents were also provided. The results
      showed that the highest estimations pertained to provinces which were mostly
      located along mountain chains, some of which are categorized as deprived
      provinces in Iran. CONCLUSIONS: The study revealed the need for further
      investigation of the role of economic and climatic factors in high risk areas.
      The application of geographical mapping together with statistical approaches can
      provide more accurate tools for policy makers to make better decisions in order
      to prevent and reduce the risks and adverse outcomes of work-related accidents.

PMID- 28510467
TI  - Association between Physicians' Adherence to a Pharmacotherapy Guideline and
      Continuity of Care for Patients with Depression and/or Anxiety Disorder.
AB  - OBJECTIVE: The aim of the paper is to investigate the association between
      physicians' adherence to a pharmacotherapy guideline and continuity of care for
      patients with depressive and/or anxiety disorders in a collaborative care
      program. METHODS: This retrospective observational study was conducted using
      medical records of subjects suffering from depression and/or anxiety disorder
      visited by 26 general practitioners (GP) working with  Community Mental Health
      Center (CMHC), who run a collaborative care program in Tehran, Iran. All patients
      were visited by a general practitioner in private offices from November 2010 to
      May 2013. A scoring system was utilized to assess physicians' adherence to the
      pharmacotherapy guideline using medical records. Patients' continuity of care was
      calculated based on the number of days of being in the collaborative care
      program. To investigate the association between physicians' adherence to the
      guideline and the patients' continuity of care, univariate logistic regression
      analysis, multiple logistic regression analysis and parametric survival analysis
      were performed using Stata version 11. RESULT:  A total of 3,338 patients were
      studied. Their mean age was 37 years and 81.6% were female. Being treated by a
      particular GP was an important factor in patients with depressive and/or anxiety
      diagnosis as well as having both diagnoses. Furthermore, higher score of
      adherence to the guideline was associated with less continuity of care in
      depressive patients. CONCLUSION: Being treated by certain GPs is an effective way
      of retention of patients in the treatment. The results demonstrate that patients
      with guideline-based pharmacotherapy need to be told about continuity of care in
      community mental health program.

PMID- 28510468
TI  - Diagnostic Efficacy of Coronary Artery Three-Dimensional Steady-State Free
      Precession Magnetic Resonance Angiography in Comparison with Invasive Coronary
      Angiography for Detecting Coronary Artery Disease.
AB  - PURPOSE: To assess the diagnostic value of three-dimensional steady-state free
      precession magnetic resonance angiography (3D-SSFP MRA) for detecting coronary
      artery disease (CAD). MATERIALS AND METHODS: Patients suspected of CAD based on
      clinical evaluation, underwent invasive coronary angiography (CAG) and Cardiac
      MRA (CMRA). Collected data in favor of any CAD findings in CMRA were compared to
      CAG results as the standard diagnostic method in CAD detection. Analysis was
      performed on per-patient, per-vessel and per-segment bases. RESULTS: A total of
      30 patients (mean age: 43 +/- 10 years, 19 men) were enrolled for analysis. On
      per-patient analysis, sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV) and area under receiver operator characteristic
      (ROC) curve of CMRA for detection of coronary artery stenosis were 100% (CI95%:
      75% - 100%), 50% (CI95%: 18% - 81%), 73.33% (CI95%: 46% - 90%), 100% (CI95%: 47% 
      100%) and 0.827, respectively. On per-vessel analysis, CMRA had a sensitivity of
      89.29% (CI95%: 71%-97%), specificity of 80.56% (CI95%: 63% - 91%), PPV of 78.13%
      (CI95%: 60% - 90%), NPV of 90.63% (CI95%: 74% - 98%) and area under ROC curve of
      0.845. On per-segment analysis, sensitivity, specificity, PPV and NPV of CMRA for
      segmental stenosis detection were 77.78% (CI95%: 60% - 89%), 87% (CI95%: 81% -
      92%), 62% (CI95%: 46% - 76%), and 93.89% (CI95%:  88% - 97%), respectively. Area
      under ROC curve was 0.835 on per-segment analysis. CONCLUSION: 3D SSFP CMRA
      provides a promising non-invasive diagnostic tool for assessing coronary artery
      disease.

PMID- 28510469
TI  - Outer Dense Fiber Proteins: Bridging between Male Infertility and Cancer.
AB  - BACKGROUND: The similarities between gametogenic and carcinogenesis processes
      have been noted for more than decades. Among prominent similarities between these
      two processes is expression of a group of antigens, namely cancer-testis antigens
      in both the testes and various cancer tissues. Outer dense fiber (ODF) proteins
      are testis-specific proteins localized to sperm tails and involved in sperm
      motility. METHODS: We performed a computerized search of the MEDLINE/PUBMED
      databases with keywords "outer dense fiber, ODF, cancer, testis, gametogenesis
      and infertility". RESULTS: The results of animal and human studies show ODF
      contribution to male fertility. In addition, ODFs are expressed in some cancers,
      including prostate adenocarcinoma, breast cancer, chronic myeloid leukemia and
      basal cell carcinoma. CONCLUSION: ODF expression analysis in cancer may pave the
      way for identification of cancer biomarkers or therapeutic targets.

PMID- 28510470
TI  - The Life and Career of Dr. Mansour Shamsa, A Pioneer in Public Health.

PMID- 28510471
TI  - Effects of Socio-economic Status Inequality on Health Outcomes.

PMID- 28510472
TI  - Dental Disaster Squad: Necessity of the Hour in Iran.

PMID- 28510473
TI  - Labor Market Outcomes: Expanding the List of Patient-centered Outcomes in
      Critical Care.

PMID- 28510474
TI  - Increased Magnetic Resonance Imaging Signal of the Lateral Patellar Facet
      Cartilage: A Functional Marker for Patellar Instability?
AB  - BACKGROUND: In the knee joint, predisposition for patellar instability can be
      assessed by an abnormal Insall-Salvati index, tibial tuberosity-trochlear groove
      (TTTG) distance, and abnormal shape of patella and trochlea. Given the complex
      anatomic features of the knee joint with varying positions of the patella during
      motion, the presence of a single or even a combination of these factors does not
      inevitably result in patellar instability. After trocheoplasty in patients with
      trochlear dysplasia, assessment of trochlear cartilage and subchondral bone is
      limited due to postoperative artifacts. Identification of presence of edema in
      the patellar cartilage may be helpful to identify patellar instability before and
      after surgery in these patients. PURPOSE: To determine whether increased signal
      intensity of the lateral patellar facet cartilage or measurements of abnormal
      patellofemoral articulation are associated with patellar instability before and
      after trochleoplasty. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Twenty-two patients with clinical diagnosis of patellar instability who underwent
      trochleoplasty, with magnetic resonance imaging (MRI) of the knee before and
      after surgery, were identified. The following observations and measurements were
      obtained in preoperative imaging: Insall-Salvati ratio, tibial tuberosity
      trochlear groove (TTTG) distance, patellar shape (Wiberg), trochlear shape
      (Hepp), and edema in the lateral patellar facet cartilage. At 3 to 12 months
      after surgery, the presence or absence of edema in the cartilage of the lateral
      facet of the patella, the trochlear shape, and TTTG distance were reassessed.
      Wilcoxon matched-pairs signed rank test and Student t test were used. Interreader
      agreement was calculated as the Cohen kappa or paired Student t test. RESULTS:
      Increased cartilage signal was present in 20 patients before trochleoplasty and
      in 4 after trochleoplasty. Insall-Salvati ratio was greater than 1.20 in 20
      patients. Patellar shape was greater than type 2 in 18 patients. Trochlear shape
      was greater than type 2 in 21 patients before and 7 after trochleoplasty. Mean
      TTTG distance was 14 mm before and 10 mm after surgery. When results before and
      after surgery were compared, a significant difference was found for cartilage
      signal, TTTG distance, and trochlear shape. Agreement for observations was
      moderate to substantial, and no significant differences were found for
      interreader agreement ( P > .05). CONCLUSION: Patellar cartilage at the lateral
      facet of the patella can be assessed after trochleoplasty despite postoperative
      artifacts in the trochlea. A decrease of patellar edema seems to be associated
      with improved femoropatellar articulation. Moreover, patellar edema may be used
      as a functional criterion of patellofemoral instability. This would provide
      additional information compared to morphologic criteria which just describe
      predisposing factors for femoropatellar instability.

PMID- 28510475
TI  - Radiation-induced Angiosarcoma as a Cause of Pleural Effusion.

PMID- 28510476
TI  - Looking beyond the Tip of a Tusk: Balancing the Evidence in Prognosis-related
      Communication.

PMID- 28510477
TI  - Performance-Based Outcomes After Anterior Cruciate Ligament Reconstruction in
      Professional Athletes Differ Between Sports.
AB  - BACKGROUND: Excellent outcomes have been reported for anterior cruciate ligament
      (ACL) reconstruction (ACLR) in professional athletes in a number of different
      sports. However, no study has directly compared these outcomes between sports.
      PURPOSE: To determine if differences in performance-based outcomes exist after
      ACLR between professional athletes of each sport. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: National Football League (NFL), National
      Basketball Association (NBA), National Hockey League (NHL), and Major League
      Baseball (MLB) athletes undergoing primary ACLR for an acute rupture were
      identified through an established protocol of injury reports and public archives.
      Sport-specific performance statistics were collected before and after surgery for
      each athlete. Return to play (RTP) was defined as a successful return to the
      active roster for at least 1 regular-season game after ACLR. RESULTS: Of 344
      professional athletes who met the inclusion criteria, a total of 298 (86.6%)
      returned to play. NHL players had a significantly higher rate of RTP (95.8% vs
      83.4%, respectively; P = .04) and a shorter recovery time (258 +/- 110 days vs
      367 +/- 268 days, respectively; P < .001) than athletes in all the other sports.
      NFL athletes experienced significantly shorter careers postoperatively than
      players in all the other sports (2.1 vs 3.2 years, respectively; P < .001). All
      athletes played fewer games ( P <= .02) 1 season postoperatively, while those in
      the NFL had the lowest rate of active players 2 and 3 seasons postoperatively
      (60%; P = .002). NBA and NFL players showed decreased performance at season 1
      after ACLR ( P <= .001). NFL players continued to have lower performance at
      seasons 2 and 3 ( P = .002), while NBA players recovered to baseline performance.
      CONCLUSION: The data indicate that NFL athletes fare the worst after ACLR with
      the lowest survival rate, shortest postoperative career length, and sustained
      decreases in performance. NHL athletes fare the best with the highest rates of
      RTP, highest survival rates, longest postoperative career lengths, and no
      significant changes in performance. The unique physical demand that each sport
      requires is likely one of the explanations for these differences in outcomes.

PMID- 28510478
TI  - Two-Tunnel Transtibial Repair of Radial Meniscus Tears Produces Comparable
      Results to Inside-Out Repair of Vertical Meniscus Tears.
AB  - BACKGROUND: Radial meniscus tears disrupt the circumferential fibers and thereby
      compromise meniscus integrity. Historically, radial tears were often treated with
      meniscectomy because of an incomplete understanding of the biomechanical
      consequences of these tears, limited information regarding the biomechanical
      performance of repair, and the technical difficulty associated with repair. There
      is a paucity of studies on the outcomes of the repair of radial meniscus tears.
      Purpose/Hypothesis: The purpose was to determine the outcomes of 2-tunnel
      transtibial repair of radial meniscus tears and compare these results to the
      outcomes of patients who underwent the repair of vertical meniscus tears with a
      minimum of 2-year follow-up. The hypothesis was that radial and vertical meniscus
      tear repair outcomes were comparable. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: Patients who underwent 2-tunnel transtibial pullout repair
      for a radial meniscus tear were included in this study and compared with patients
      who underwent inside-out repair for a vertical meniscus tear. Subjective
      questionnaires were administered preoperatively and at a minimum of 2-year follow
      up, including the Lysholm score, the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC), the Short Form-12 (SF-12) physical component
      summary (PCS), the Tegner activity scale, and patient satisfaction. Analysis of
      covariance was used to compare postoperative outcome scores between the meniscus
      repair groups while accounting for baseline scores. Adjusted mean effects
      relative to the radial repair group were reported with 95% CIs. RESULTS: Twenty
      seven patients who underwent 2-tunnel transtibial pullout repair for radial
      meniscus tears and 33 patients who underwent inside-out repair for vertical
      meniscus tears were available for follow-up at a mean of 3.5 years (range, 2.0
      5.4 years). No preoperative outcome score significantly differed between the
      groups. There were no significant group differences for any of the 2-year
      postoperative outcome scores. Relative to the vertical repair group, the radial
      repair group exhibited an adjusted mean of -0.2 (95% CI, -5.4 to 4.9), -0.6 (95%
      CI, -6.6 to 5.5), and 5.1 (95% CI, -3.9 to 14.0) points on the SF-12 PCS, WOMAC,
      and Lysholm scores, respectively. CONCLUSION: The 2-tunnel transtibial pullout
      technique for the repair of radial meniscus tears produces similar clinical
      outcomes when compared with the repair of vertical meniscus tears at a mean 3.5
      years' follow-up.

PMID- 28510479
TI  - Increased Expression of p22phox Mediates Airway Hyperresponsiveness in an
      Experimental Model of Asthma.
AB  - AIM: Chronic airway diseases such as asthma are associated with increased
      production of reactive oxygen species (ROS) and oxidative stress. Endogenous
      NADPH oxidases are a major source of superoxide in lung, but their underlying
      role in asthma pathology is poorly understood. We sought to characterize the
      involvement of NADPH oxidase in allergic asthma by studying the role of CYBA
      (p22phox) in human asthma and murine house dust mite (HDM)-induced allergic
      airway inflammation. RESULTS: Increased expression and localization of p22-PHOX
      were observed in biopsies of asthmatic patients. HDM-treated wild-type mice
      possessed elevated p22phox expression, corresponding with elevated superoxide
      production. p22phox knockout (KO) mice did not induce superoxide and were
      protected against HDM-induced goblet cell hyperplasia and mucus production and
      HDM-induced airway hyperresponsiveness (AHR). IL-13-induced tracheal
      hyperreactivity and signal transducer and activator of transcription (STAT)6
      phosphorylation were attenuated in the absence of p22phox or catalase
      pretreatment. INNOVATION: Our study identifies increased expression of p22phox in
      lungs of asthmatic patients and in experimental model. The induced AHR and mucus
      hypersecretion are a result of increased ROS from the p22phox-dependent NADPH
      oxidase, which in turn activates STAT6 for the pathological feature of asthma.
      CONCLUSIONS: Together with the increased p22phox expression in lungs of asthmatic
      patients, these findings demonstrate a crucial role of p22phox-dependent NADPH
      oxidase for the development of mucus hypersecretion and AHR in HDM-induced model
      of asthma. This suggests that inhibition of functional NADPH oxidase by selective
      interference of p22phox might hold a promising therapeutic strategy for the
      management of asthma. Antioxid. Redox Signal. 27, 1460-1472.

PMID- 28510480
TI  - Dry-Powder Inhaler Formulation of Rifampicin: An Improved Targeted Delivery
      System for Alveolar Tuberculosis.
AB  - BACKGROUND: The delivery of antitubercular drugs through direct lung targeting
      can lead to reduction in the dose as well as side effects of the drug. In the
      present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin
      was prepared to achieve direct targeting of the drug into the lungs. METHODS: The
      dry powder inhaler formulation was prepared by simply mixing micronized
      rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug
      were prepared with various lactose grades (Inhalac(r), Respitose,(r) and
      Lactohale(r)). Rotahaler(r) and Revolizer(r) were evaluated for the performance.
      The 32 factorial design was used to optimize the amount of drug (X1) and amount
      of fine lactose (X2). In vitro lung deposition was carried out using Andersen
      Cascade Impactor. The % cell viability studies of the formulation were carried
      out using murine macrophage J774 cell lines. The in vivo toxicity was determined
      using histopathology. Further in vivo pulmonary pharmacokinetics of the developed
      dry-powder inhaler (DPI) formulation was carried out in comparison to the
      marketed formulation in the rat lungs. RESULTS: Based on preliminary trials,
      Inhalac 230 and Inhalac 400 were selected as coarse and fine lactose grades,
      respectively. Rotahaler(r) exhibited better DPI performance with the evaluated
      drug blends. The mass median aerodynamic diameter (MMAD) was in the range of 4.3
      5.8 MUm with the maximum fine particle fraction of 28.9%. The formulation
      exhibited negligible cytotoxicity on macrophage J774 cell lines with about 75%
      80% cell viability at 6- and 12-hour exposure. The histopathological examination
      revealed negligible toxicity of DPI in comparison to the marketed formulation.
      The in vivo pulmonary pharmacokinetic studies of the DPI formulation in rats
      showed higher drug concentration in lungs in comparison to the marketed
      formulation. CONCLUSION: The carrier-mediated dry-powder inhaler of rifampicin
      could serve as an improved and efficient system for local targeting of drugs into
      the lungs.

PMID- 28510481
TI  - Family Group Conferencing-Its Added Value in Mental Health Care.
AB  - Worldwide, there is a growing emphasis on reducing coercion and involving social
      networks in the care of mental health clients. Nurses should encourage their
      clients to regain control over their lives, preferably with less coercion and
      with help from their social network. During four years, a Dutch evaluation study
      was deployed to determine the applicability of mobilising help from social
      networks of people with psychiatric problems. Specifically the potential of
      Family Group Conferencing was examined. In this discursive article the question,
      'what Family Group Conferencing adds to the existing methods that aim to reduce
      coercion in mental health care and promote inclusion' is addressed.

PMID- 28510483
TI  - Improvement in Ventilation-Perfusion Mismatch after Bronchoscopic Lung Volume
      Reduction: Quantitative Image Analysis.
AB  - Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases
      ventilation and therefore improves ventilation-perfusion (V/Q) mismatch.
      Materials and Methods All patients provided written informed consent to be
      included in this study, which was approved by the Institutional Review Board
      (2013-0368) of Asan Medical Center. The physiologic changes that occurred after
      BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced
      perfusion dual-energy computed tomography (CT). Patients with severe emphysema
      plus hyperinflation who did not respond to usual treatments were eligible.
      Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of
      life assessment, and dual-energy CT were performed at baseline and 3 months after
      BLVR. The effect of BLVR was assessed with repeated-measures analysis of
      variance. Results Twenty-one patients were enrolled in this study (median age, 68
      years; mean forced expiratory volume in 1 second [FEV1], 0.75 L +/- 0.29). After
      BLVR, FEV1 (P < .001) and 6MWD (P = .002) improved significantly. Despite the
      reduction in lung volume (-0.39 L +/- 0.44), both ventilation per voxel (P <
      .001) and total ventilation (P = .01) improved after BLVR. However, neither
      perfusion per voxel (P = .16) nor total perfusion changed significantly (P =
      .49). Patients with lung volume reduction of 50% or greater had significantly
      better improvement in FEV1 (P = .02) and ventilation per voxel (P = .03) than
      patients with lung volume reduction of less than 50%. V/Q mismatch also improved
      after BLVR (P = .005), mainly owing to the improvement in ventilation. Conclusion
      The dual-energy CT analyses showed that BLVR improved ventilation and V/Q
      mismatch. This increased lung efficiency may be the primary mechanism of
      improvement after BLVR, despite the reduction in lung volume. (c) RSNA, 2017
      Online supplemental material is available for this article.

PMID- 28510484
TI  - Ethylene Signaling Is Important for Isoflavonoid-Mediated Resistance to
      Rhizoctonia solani in Roots of Medicago truncatula.
AB  - The root-infecting necrotrophic fungal pathogen Rhizoctoniasolani causes
      significant disease to all the world's major food crops. As a model for
      pathogenesis of legumes, we have examined the interaction of R. solani AG8 with
      Medicago truncatula. RNAseq analysis of the moderately resistant M. truncatula
      accession A17 and highly susceptible sickle (skl) mutant (defective in ethylene
      sensing) identified major early transcriptional reprogramming in A17. Responses
      specific to A17 included components of ethylene signaling, reactive oxygen
      species metabolism, and consistent upregulation of the isoflavonoid biosynthesis
      pathway. Mass spectrometry revealed accumulation of the isoflavonoid-related
      compounds liquiritigenin, formononetin, medicarpin, and biochanin A in A17.
      Overexpression of an isoflavone synthase in M. truncatula roots increased
      isoflavonoid accumulation and resistance to R. solani. Addition of exogenous
      medicarpin suggested this phytoalexin may be one of several isoflavonoids
      required to contribute to resistance to R. solani. Together, these results
      provide evidence for the role of ethylene-mediated accumulation of isoflavonoids
      during defense against root pathogens in legumes. The involvement of ethylene
      signaling and isoflavonoids in the regulation of both symbiont-legume and
      pathogen-legume interactions in the same tissue may suggest tight regulation of
      these responses are required in the root tissue.

PMID- 28510482
TI  - Rod Outer Segment Development Influences AAV-Mediated Photoreceptor Transduction
      After Subretinal Injection.
AB  - Vectors based on the adeno-associated virus (AAV) are currently the preferred
      tools for delivering genes to photoreceptors (PR) in small and large animals.
      AAVs have been applied successfully in various models of PR dystrophies. However,
      unknown barriers still limit AAV's efficient application in several forms of
      severe PR degenerations due to insufficient transgene expression and/or treated
      cells at the time of injection. Optimizations of PR gene therapy strategies will
      likely benefit from the identification of the cellular factors that influence PR
      transduction. Interestingly, recent studies have shown that the AAV transduction
      profile of PRs differs significantly between neonatal and adult mouse retinas
      after subretinal injection. This phenomenon may provide clues to identify host
      factors that influence the efficiency of AAV-mediated PR transduction. This study
      demonstrates that rod outer segments are critical modulators of efficient AAV
      mediated rod transduction. During retinal development, rod transduction
      correlated temporally and spatially with the differentiation order of PRs when
      vectors were introduced subretinally but not when introduced intravitreally. All
      subretinally injected vectors had an initial preference to transduce cones in the
      absence of formed rod outer segments and then displayed a preference for rods as
      the cells matured, independently of the expression cassette or AAV serotype.
      Consistent with this observation, altered development of rod outer segments was
      associated with a strong reduction of rod transduction and an increase in the
      percentage of transduced cones by 2- to 2.8-fold. A similar increase of cone
      transduction was observed in the adult retinal degeneration 1 (rd1) retina
      compared to wild-type mice. These results suggest that the loss of rod outer
      segments in diseased retinas could markedly affect gene transfer efficiency of
      AAV vectors by limiting the ability of AAVs to infect dying rods efficiently.
      This information could be exploited for the development of more efficient AAV
      based PR gene delivery procedures.

PMID- 28510485
TI  - Metabolomic Response to Huanglongbing: Role of Carboxylic Compounds in Citrus
      sinensis Response to 'Candidatus Liberibacter asiaticus' and Its Vector,
      Diaphorina citri.
AB  - Huanglongbing, a destructive disease of citrus, is caused by the fastidious
      bacterium 'Candidatus Liberibacter asiaticus' and transmitted by Asian citrus
      psyllid, Diaphorina citri. The impact of 'Ca. L. asiaticus' infection or D. citri
      infestation on Valencia sweet orange (Citrus sinensis) leaf metabolites was
      investigated using gas chromatography mass spectrometry, followed by gene
      expression analysis for 37 genes involved in jasmonic acid (JA), salicylic acid
      (SA), and proline-glutamine pathways. The total amino acid abundance increased
      after 'Ca. L. asiaticus' infection, while the total fatty acids increased
      dramatically after infestation with D. citri, compared with control plants. Seven
      amino acids (glycine, l-isoleucine, l-phenylalanine, l-proline, l-serine, l
      threonine, and l-tryptophan) and five organic acids (benzoic acid, citric acid,
      fumaric acid, SA, and succinic acid) increased in 'Ca. L. asiaticus'-infected
      plants. On the other hand, the abundance of trans-JA and its precursor alpha
      linolenic increased in D. citri-infested plants. Surprisingly, the double attack
      of both D. citri infestation and 'Ca. L. asiaticus' infection moderated the
      metabolic changes in all chemical classes studied. In addition, the gene
      expression analysis supported these results. Based on these findings, we suggest
      that, although amino acids such as phenylalanine are involved in citrus defense
      against 'Ca. L. asiaticus' infection through the activation of an SA-mediated
      pathway, fatty acids, especially alpha-linolenic acid, are involved in defense
      against D. citri infestation via the induction of a JA-mediated pathway.

PMID- 28510486
TI  - Advice for my chief resident.
AB  - I have been privileged to have served as a division of rheumatology chief and/or
      program director for 18 years and as a department of medicine chair and medicine
      residency program director for another 22 years. During the latter, I collected
      and codified advice for my chief residents. Selected highlights are presented as
      follows.

PMID- 28510488
TI  - Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem
      Cells.
AB  - BACKGROUND: For patients with short bowel syndrome under parenteral nutrition
      support, growth hormone (GH) and glutamine (GLN) have been found to help the
      growth of intestinal mucosa. In this research, we studied the effects of GH and
      GLN on intestinal stem cells (ISCs). METHODS: The in vitro and in vivo effects of
      GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form
      organoids in a Matrigel culture system. The expression levels of stemness and
      differentiation markers in ISCs and organoids were assessed using quantitative
      real-time polymerase chain reaction, immunofluorescence assay, and
      immunohistochemistry staining. RESULTS: In vitro administration of GH activated
      the stemness of ISCs, whereas GLN enhanced the expression of chromogranin A and
      Muc2, which are differentiation markers in enteroendocrine and goblet cells,
      respectively. Administration of GH or GLN in mice showed that GH, but not GLN,
      upregulated the proliferative activity of ISCs with increased formation of crypt
      organoids. In addition, GH increased the expression of Lgr5 and GLN enhanced
      expression of Muc2 in the crypt fractions of the intestines in mice. CONCLUSION:
      These results suggest that GH mainly enhances proliferative activities, whereas
      GLN promotes the differentiation potential of ISCs.

PMID- 28510487
TI  - Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and
      an approach for their re-evaluation.
AB  - The threshold of toxicological concern (TTC) approach is a resource-effective de
      minimis method for the safety assessment of chemicals, based on distributional
      analysis of the results of a large number of toxicological studies. It is being
      increasingly used to screen and prioritize substances with low exposure for which
      there is little or no toxicological information. The first step in the approach
      is the identification of substances that may be DNA-reactive mutagens, to which
      the lowest TTC value is applied. This TTC value was based on the analysis of the
      cancer potency database and involved a number of assumptions that no longer
      reflect the state-of-the-science and some of which were not as transparent as
      they could have been. Hence, review and updating of the database is proposed,
      using inclusion and exclusion criteria reflecting current knowledge. A strategy
      for the selection of appropriate substances for TTC determination, based on
      consideration of weight of evidence for genotoxicity and carcinogenicity is
      outlined. Identification of substances that are carcinogenic by a DNA-reactive
      mutagenic mode of action and those that clearly act by a non-genotoxic mode of
      action will enable the protectiveness to be determined of both the TTC for DNA
      reactive mutagenicity and that applied by default to substances that may be
      carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class
      I-III compounds). Critical to the application of the TTC approach to substances
      that are likely to be DNA-reactive mutagens is the reliability of the software
      tools used to identify such compounds. Current methods for this task are reviewed
      and recommendations made for their application.

PMID- 28510490
TI  - ?

PMID- 28510489
TI  - Urban heat island (UHI) influence on secondary pollutant formation in a tropical
      humid environment.
AB  - : The combined action of urbanization (change in land use) and increase in
      vehicular emissions intensifies the urban heat island (UHI) effect in many cities
      in the developed countries. The urban warming (UHI) enhances heat-stress-related
      diseases and ozone (O3) levels due to a photochemical reaction. Even though UHI
      intensity depends on wind speed, wind direction, and solar flux, the
      thermodynamic properties of surface materials can accelerate the temperature
      profiles at the local scale. This mechanism modifies the atmospheric boundary
      layer (ABL) structure and mixing height in urban regions. These changes further
      deteriorate the local air quality. In this work, an attempt has been made to
      understand the interrelationship between air pollution and UHI intensity at
      selected urban areas located at tropical environment. The characteristics of
      ambient temperature profiles associated with land use changes in the different
      microenvironments of Chennai city were simulated using the Envi-Met model. The
      simulated surface 24-hr average air temperatures (11 m above the ground) for
      urban background and commercial and residential sites were found to be 30.81 +/-
      2.06, 31.51 +/- 1.87, and 31.33 +/- 2.1oC, respectively. The diurnal variation of
      UHI intensity was determined by comparing the daytime average air temperatures to
      the diurnal air temperature for different wind velocity conditions. From the
      model simulations, we found that wind speed of 0.2 to 5 m/sec aggravates the UHI
      intensity. Further, the diurnal variation of mixing height was also estimated at
      the study locations. The estimated lowest mixing height at the residential area
      was found to be 60 m in the middle of night. During the same period, highest
      ozone (O3) concentrations were also recorded at the continuous ambient air
      quality monitoring station (CAAQMS) located at the residential area.
      IMPLICATIONS: An attempt has made to study the diurnal variation of secondary
      pollution levels in different study regions. This paper focuses mainly on the UHI
      intensity variations with respect to percentage of land use pattern change in
      Chennai city, India. The study simulated the area-based land use pattern with
      local mixing height variations. The relationship between UHI intensity and mixing
      height provides variations on local air quality.

PMID- 28510492
TI  - Frequency of Germline BRCA1/2 Mutations in Unselected Patients With Colorectal
      Cancer.

PMID- 28510491
TI  - Short-Term Growth During Treatment with Inhaled Fluticasone
      Propionate/Formoterol, Fluticasone and Beclomethasone Treatment.
AB  - BACKGROUND: Fluticasone propionate/formoterol (FP/FORM) is a pressurized metered
      dose inhaler (pMDI; Flutiform(r)) approved for use in adolescents and adults and
      under development for pediatric use. OBJECTIVE: To compare short-term growth in
      asthmatic children treated with FP/FORM, FP pMDI with valved holding chamber, and
      beclomethasone dipropionate (BDP) in a breath-actuated device. METHODS: Children
      with persistent asthma (n = 48; 5 to <12 years) participated in an assessor
      blinded, randomized, three-way crossover trial with run in, wash out, and active
      treatment periods, each of 2 weeks duration. Interventions were FP/FORM 100/10
      MUg b.i.d. with an AeroChamber Plus(r) Flow-Vu(r) Spacer, FP pMDI (Flixotide(r))
      100 MUg b.i.d. with a Volumatic(r) spacer, and extra-fine BDP breath-actuated
      inhaler (Aerobec(r)/QVAR(r) Autohaler(r)) 100 MUg b.i.d. Lower leg growth rate
      (LLGR) was measured by knemometry. RESULTS: The least square (LS) mean difference
      in LLGR between FP/FORM and FP (per protocol population) was -0.006 mm/week (95%
      CI: -0.095 to 0.084; p < 0.001 for noninferiority [noninferiority margin -0.200
      mm/week]). Both treatments elicited no change from baseline off-treatment growth
      rate. The LS mean treatment difference of FP/FORM versus BDP was 0.116 mm/week
      (95% CI: -0.004 to 0.235; p = 0.057) and of FP versus BDP 0.163 mm/week (95% CI:
      0.078-0.249; p < 0.001). Results in the full analysis population were: FP/FORM
      versus FP -0.012 mm/week (95% CI: -0.080-0.056; p < 0.001); FP/FORM versus BDP
      0.143 mm/week (95% CI: 0.064-0.222; p < 0.001); FP versus BDP 0.163 mm/week (95%
      CI: 0.093-0.233; p < 0.001). CONCLUSIONS: FP/FORM pMDI with AeroChamber and FP
      pMDI with Volumatic spacer did not affect lower leg growth, measured by
      knemometry, in asthmatic children. Conversely, extra-fine BDP from a breath
      actuated inhaler resulted in short-term growth suppression.

PMID- 28510493
TI  - Not All BRAF-Mutant Metastatic Colorectal Cancers Are Identical: Distinct
      Clinical Consequences of non-V600 BRAF Mutations.

PMID- 28510494
TI  - Reply to M.S. Daniels et al.

PMID- 28510495
TI  - Fatigue in Younger and Older Drivers: Effectiveness of an Alertness-Maintaining
      Task.
AB  - OBJECTIVE: The aim of this study was to examine the effects of an alertness
      maintaining task (AMT) in older, fatigued drivers. BACKGROUND: Fatigue during
      driving increases crash risk, and previous research suggests that alertness and
      driving in younger adults may be improved using a secondary AMT during boring,
      fatigue-eliciting drives. However, the potential impact of an AMT on driving has
      not been investigated in older drivers whose ability to complete dual tasks has
      been shown to decline and therefore may be negatively affected with an AMT in
      driving. METHOD: Younger ( n = 29) and older drivers ( n = 39) participated in a
      50-minute simulated drive designed to induce fatigue, followed by four 10-minute
      sessions alternating between driving with and without an AMT. RESULTS: Younger
      drivers were significantly more affected by fatigue on driving performance than
      were older drivers but benefitted significantly from the AMT. Older drivers did
      not demonstrate increased driver errors with fatigue, and driving did not
      deteriorate significantly during participation in the AMT condition, although
      their speed was significantly more variable with the AMT. CONCLUSION: Consistent
      with earlier research, an AMT applied during fatiguing driving is effective in
      improving alertness and reducing driving errors in younger drivers. Importantly,
      older drivers were relatively unaffected by fatigue, and use of an AMT did not
      detrimentally affect their driving performance. APPLICATION: These results
      support the potential use of an AMT as a new automotive technology to improve
      fatigue and promote driver safety, though the benefits of such technology may
      differ between different age groups.

PMID- 28510496
TI  - Comparison of the Treatment Guidelines for Actinic Keratosis: A Critical
      Appraisal and Review.
AB  - There are currently several reputable guidelines on the treatment of actinic
      keratosis (AK) from groups in Canada, the United Kingdom, and Europe. These
      recommendations, based on evidence or expert consensus, offer clinicians a
      variety of treatment options for the different clinical presentations of AKs.
      Although the guidelines are similar in some regards, variations exist in
      treatment options, duration, and strength of recommendation. Some guidelines also
      lack input on specific therapies and certain types of AK, such as hypertrophic or
      thin presentations. The purpose of this article is to review and compare
      guidelines published by Canadian, UK, and European groups for the management of
      AKs in patients.

PMID- 28510497
TI  - Clinical Development and Commercialization of Advanced Therapy Medicinal Products
      in the European Union: How Are the Product Pipeline and Regulatory Framework
      Evolving?
AB  - The research and development of advanced therapy medicinal products (ATMPs) has
      been active in Europe and worldwide during recent years. Yet, the number of
      licensed products remains low. The main expected legal change in the near future
      in the European Union (EU) concerns the regulation on clinical trials (536/2014),
      which will come into force in 2018. With this new framework, a more harmonized
      and swift process for approval of clinical trials is anticipated, which is
      expected to support the entry of new innovations into the EU market. A survey on
      ATMPs in clinical trials during 2010-2015 in the EU was conducted in order to
      study the trends of ATMP development since the earlier survey published in 2012.
      According to the results, the number of clinical trials using ATMPs is slowly
      increasing in the EU. Yet, the focus is still in early development, and the
      projects are mainly carried out by small and medium-sized enterprises, academia,
      and hospitals. Oncology is the main area of clinical development. Yet, the
      balance between cell-based products and gene therapy medicinal products in this
      area may be changing in the future due to the new T-cell technologies. Many
      limitations and challenges are identified for ATMP development, requiring
      proportionate regulatory requirements. On the other hand, for such a novel field,
      the developers should be active in considering possible constraints and actively
      engage with authorities to look for solutions. This article provides up to-date
      information on forthcoming regulatory improvements and discusses the main
      challenges hampering the commercialization of ATMPs in the EU.

PMID- 28510498
TI  - Deficits in go/no-go task performance in male undergraduate high-risk alcohol
      users are driven by speeded responding to go stimuli.
AB  - BACKGROUND: Response disinhibition plays an important role in addictive
      behaviors. However, results of studies on the performance on response inhibition
      tasks of individuals evidencing potentially problematic levels of alcohol
      drinking are mixed. OBJECTIVES: We assessed conditions under which persons with a
      relatively high risk of alcohol dependence show inhibition deficits in such tasks
      and investigated the nature of those deficits. METHODS: Fifty-eight male
      undergraduate students, 27 of which were high-risk drinkers according to the
      Alcohol Use Disorders Identification Test, performed a go/no-go inhibition task
      with differing percentages of no-go trials (50% vs. 25%), stimulus presentation
      times (600 vs. 200 ms), and types of go and no-go stimuli (alcohol related vs. 
      unrelated). Response inhibition was indexed by response time (RT) to go trials
      and response accuracy on go and no-go trials. RESULTS: There were no differences
      between low- and high-risk drinkers on any of the three outcome measures under
      the 600-ms stimulus presentation condition. Under the 200-ms condition, the high
      risk drinkers showed faster RTs to go stimuli, and more errors on both go- and no
      go trials than the low-risk drinkers, irrespective of type and percentage of no
      go stimuli. However, the accuracy differences between the two groups disappeared
      after controlling for the RT on go trials, suggesting a speed-accuracy trade-off.
      CONCLUSION: High-risk drinkers' response inhibition deficits are not restricted
      to alcohol-related cues and are especially likely to occur under conditions
      prompting fast responding. These findings could be used to inform treatment,
      suggesting the promotion of strategies aimed at preventing high-risk alcohol
      users from making quick decisions.

PMID- 28510499
TI  - George Lewith, MD, DM, FRCP, MRCGP (1950-2017).

PMID- 28510500
TI  - Using "big data" to guide implementation of a web and mobile adaptive learning
      platform for medical students.
AB  - BACKGROUND: Adaptive learning platforms (ALPs) can revolutionize medical
      education by making learning more efficient, but their potential has not been
      realized because students do not use them persistently. METHODS: We applied
      educational data mining methods to study United States medical students who used
      an ALP called Osmosis ( www.osmosis.org ) from 1 August 2014 to 31 July 2015.
      Multivariate logistic regressions modeled persistence on Osmosis as the dependent
      variable and Osmosis-collected variables as predictors. RESULTS: The 6787
      students included in our analysis responded to a total of 887,193 items, with
      2138 (31.5%) using Osmosis persistently. Number of items per student, mobile
      device use, subscription payment, and group membership were independently
      associated with persisting (p < 0.001 in all models). Persistent users rated
      quality more favorably (p < 0.01) but were not more confident in answer
      selections (p = 0.80). While persisters were more accurate than non-persisters
      (55% (SD 18%) vs 52% (SD 22%), p < 0.001), after adjusting for number of items,
      lower accuracy was associated with persistent use (OR 0.93 [95% CI 0.90-0.97], p
      < 0.01). CONCLUSIONS: Our study of a large sample of U.S. medical students
      illustrates big data medical education research and provides guidance for
      improving implementation of ALPs and further investigation.

PMID- 28510501
TI  - Mechanical ventilation in the acute respiratory distress syndrome.
AB  - The management of the acute respiratory distress syndrome (ARDS) patient is
      fundamental to the field of intensive care medicine, and it presents unique
      challenges owing to the specialized mechanical ventilation techniques that such
      patients require. ARDS is a highly lethal disease, and there is compelling
      evidence that mechanical ventilation itself, if applied in an injurious fashion,
      can be a contributor to ARDS mortality. Therefore, it is imperative for any
      clinician central to the care of ARDS patients to understand the fundamental
      framework that underpins the approach to mechanical ventilation in this special
      scenario. The current review summarizes the major components of the mechanical
      ventilation strategy as it applies to ARDS.

PMID- 28510503
TI  - Are we becoming inaccessible caregivers?
AB  - This essay is a personal reflection of my mindset as a caregiver, and how that
      has evolved throughout my training.

PMID- 28510502
TI  - The Impact of Steroidal Glycoalkaloids on the Physiology of Phytophthora
      infestans, the Causative Agent of Potato Late Blight.
AB  - Steroidal glycoalkaloids (SGAs) are plant secondary metabolites known to be toxic
      to animals and humans and that have putative roles in defense against pests. The
      proposed mechanisms of SGA toxicity are sterol-mediated disruption of membranes
      and inhibition of cholinesterase activity in neurons. It has been suggested that
      phytopathogenic microorganisms can overcome SGA toxicity by enzymatic
      deglycosylation of SGAs. Here, we have explored SGA-mediated toxicity toward the
      invasive oomycete Phytophthora infestans, the causative agent of the late blight
      disease in potato and tomato, as well as the potential for SGA deglycosylation by
      this species. Our growth studies indicate that solanidine, the nonglycosylated
      precursor of the potato SGAs alpha-chaconine and alpha-solanine, has a greater
      physiological impact than its glycosylated forms. All of these compounds were
      incorporated into the mycelium, but only solanidine could strongly inhibit the
      growth of P. infestans in liquid culture. Genes encoding several glycoside
      hydrolases with potential activity on SGAs were identified in the genome of P.
      infestans and were shown to be expressed. However, we found no indication that
      deglycosylation of SGAs takes place. We present additional evidence for apparent
      host-specific adaptation to potato SGAs and assess all results in terms of future
      pathogen management strategies.

PMID- 28510504
TI  - Cardiopulmonary Exercise Testing: Basics of Methodology and Measurements.
AB  - Cardiopulmonary exercise testing adds measurement of ventilation and volume of
      oxygen uptake and exhaled carbon dioxide to routine physiological and performance
      parameters obtainable from conventional exercise testing, furnishing an all
      around vision of the systems involved in both oxygen transport from air to
      mitochondria and its use during exercise. Peculiarities of cardiopulmonary
      exercise testing methodology are the use of ramp protocols and calibration
      procedures for flow meters and gas analyzers. Among the several parameters
      provided by this technique, peak oxygen uptake, first and second ventilatory
      thresholds, respiratory exchange ratio, oxygen pulse, slope of ventilation
      divided by exhaled carbon dioxide relationship, exercise oscillatory ventilation,
      circulatory power, and partial pressure of end-tidal carbon dioxide are among the
      most relevant in the clinical setting. The choice of parameters to be considered
      will depend on the indication to cardiopulmonary exercise testing in the
      individual subject or patient, namely, exercise tolerance assessment, prognostic
      stratification, training prescription, treatment efficacy evaluation, diagnosis
      of causes of unexplained exercise tolerance reduction, or exercise
      (patho)physiology evaluation for research purposes. Overall, cardiopulmonary
      exercise testing is a methodology now widely available and supported by sound
      scientific evidence. Despite this, its potential still remains largely underused.
      Strong efforts and future investigations are needed to address these issues and
      further promote the use of cardiopulmonary exercise testing in the clinical and
      research setting.

PMID- 28510507
TI  - Five Steps to Engage in the Concept of Whole Health Begins With Mental Health.

PMID- 28510506
TI  - Signaling at the Crossroads: Matrix-Derived Proteoglycan and Reactive Oxygen
      Species Signaling.
AB  - SIGNIFICANCE: Proteoglycans (PGs), besides their structural contribution, have
      emerged as dynamic components that mediate a multitude of cellular events. The
      various roles of PGs are attributed to their structure, spatial localization, and
      ability to act as ligands and receptors. Reactive oxygen species (ROS) are small
      mediators that are generated in physiological and pathological conditions.
      Besides their reactivity and ability to induce oxidative stress, a growing body
      of data suggests that ROS signaling is more relevant than direct radical damage
      in development of human pathologies. Recent Advances: Cell surface transmembrane
      PGs (syndecans, cluster of differentiation 44) represent receptors in diverse and
      complex transduction networks, which involve redox signaling with implications in
      cancer, fibrosis, renal dysfunction, or Alzheimer's disease. Through NADPH
      oxidase (NOX)-dependent ROS, the extracellular PG, hyaluronan is involved in
      osteoclastogenesis and cancer. The ROS sources, NOX1 and NOX4, increase biglycan
      induced inflammation, while NOX2 is a negative regulator. CRITICAL ISSUES: The
      complexity of the mechanisms that bring ROS into the light of PG biology might be
      the foundation of a new research area with significant promise for understanding
      health and disease. Important aspects need to be investigated in PG/ROS
      signaling: the discovery of specific targets of ROS, the precise ROS-induced
      chemical modifications of these targets, and the study of their pathological
      relevance. FUTURE DIRECTIONS: As we become more and more aware of the
      interactions between PG and ROS signaling underlying intracellular communication
      and cell fate decisions, it is quite conceivable that this field will allow to
      identify new therapeutic targets.-Antioxid. Redox Signal. 27, 855-873.

PMID- 28510505
TI  - Papillary Thyroid Cancer: The Good and Bad of the "Good Cancer".
AB  - BACKGROUND: Papillary thyroid cancer is often described as the "good cancer"
      because of its treatability and relatively favorable survival rates. This study
      sought to characterize the thoughts of papillary thyroid cancer patients as they
      relate to having the "good cancer." METHODS: This qualitative study included 31
      papillary thyroid cancer patients enrolled in an ongoing randomized trial. Semi
      structured interviews were conducted with participants at the preoperative visit
      and two weeks, six weeks, six months, and one year after thyroidectomy. Grounded
      theory was used, inductively coding the first 113 interview transcripts with
      NVivo 11. RESULTS: The concept of thyroid cancer as "good cancer" emerged
      unprompted from 94% (n = 29) of participants, mostly concentrated around the time
      of diagnosis. Patients encountered this perception from healthcare providers,
      Internet research, friends, and preconceived ideas about other cancers. While
      patients generally appreciated optimism, this perspective also generated negative
      feelings. It eased the diagnosis of cancer but created confusion when individual
      experiences varied from expectations. Despite initially feeling reassured,
      participants described feeling the "good cancer" characterization invalidated
      their fears of having cancer. Thyroid cancer patients expressed that they did not
      want to hear that it's "only thyroid cancer" and that it's "no big deal," because
      "cancer is cancer," and it is significant. CONCLUSIONS: Patients with papillary
      thyroid cancer commonly confront the perception that their malignancy is "good,"
      but the favorable prognosis and treatability of the disease do not
      comprehensively represent their cancer fight. The "good cancer" perception is at
      the root of many mixed and confusing emotions. Clinicians emphasize optimistic
      outcomes, hoping to comfort, but they might inadvertently invalidate the impact
      thyroid cancer has on patients' lives.

PMID- 28510509
TI  - Psychometric Properties of the Psychological Vulnerability Scale in Higher
      Education Students.
AB  - BACKGROUND: Psychological vulnerability is related to cognitive beliefs that
      reflect dependence on one's sense of self-worth and to maladaptive functioning.
      It is a disadvantage that renders people less protected to face negative life
      experiences. OBJECTIVE: The purpose of this study was to adapt and test the
      psychometric properties of the Psychological Vulnerability Scale in a sample of
      267 Portuguese higher education students. DESIGN: A psychometric study of the
      Psychological Vulnerability Scale, after translation into Portuguese, was
      performed with a convenience sample of higher education students. Participants
      were asked to fill in the sociodemographic questionnaire, the Psychological
      Vulnerability Scale, the Brief Symptom Inventory, and a one-item question about
      the Perception of Vulnerability. RESULTS: The mean age of the participants was
      20.5 years ( SD = 3.3). A factor analysis confirmed the original one-factor
      structure, explaining 42.9% of the total variance. The Psychological
      Vulnerability Scale showed adequate internal consistency and excellent test
      retest stability. Convergent validity was confirmed by positive correlations with
      the Brief Symptom Inventory and Perception of Vulnerability. CONCLUSIONS:
      Overall, the Psychological Vulnerability Scale showed good validity, reliability,
      and stability over time. The Psychological Vulnerability Scale is now ready to be
      used by practitioners and researchers to measure the psychological vulnerability
      among Portuguese higher education students. These data add to the body of
      knowledge of psychiatric and mental health nursing and provides support for the
      use of the Psychological Vulnerability Scale in higher education students.

PMID- 28510510
TI  - A Nurse Practitioner's View on Telehealth.

PMID- 28510511
TI  - Corrigendum.
AB  - Birkeland AC, Owen JH, Prince ME. 2015. Targeting head and neck cancer stem
      cells: current advances and future challenges. J Dent Res. 94(11):1516-1523.
      (Original DOI: 10.1177/0022034515601960) In this article, the funding source was
      not declared. The Acknowledgments have been updated in the online article as
      follows: Andrew Birkeland is a Research Fellow funded on a T32 Advanced Research
      Training in Otolaryngology Program Training Grant (T32 DC005356) funded by the
      National Institutes of Health NIDCD (National Institute On Deafness And Other
      Communication Disorders).

PMID- 28510514
TI  - Door Is Open for HRAs to Make a Comeback.
AB  - For four years, businesses that wanted to reimburse employees for their health
      insurance premiums rather than buying their coverage for them were told that that
      was no longer allowed under the ACA. But the health reimbursement arrangement
      (HRA) is back, brought back to life by provisions tucked into last year's 21st
      Century Cure Act.

PMID- 28510512
TI  - Field trial of insect-resistant and herbicide-tolerant genetically modified
      cotton (Gossypium hirsutum L.) for environmental risk assessment in Japan.
AB  - Japan imports cottonseed mainly from Australia and the USA where more than 96% of
      all cotton varieties grown are genetically modified (GM). GM crops undergo an
      environmental risk assessment (ERA) under the Law Concerning the Conservation and
      Sustainable Use of Biological Diversity before import into Japan. Potential
      adverse effects on biodiversity are comprehensively assessed based on
      competitiveness, production of harmful substances and outcrossing ability. Even
      though imported cottonseed is intended for food and feed uses and not for
      cultivation, the potential risks from seed spillage during transport must be
      evaluated. In most cases, the ERA requires data collected from in-country field
      trials to demonstrate how the GM crop behaves in Japan's environment. Confined
      field trials in Japan were conducted for the ERA of Lepidoptera-resistant and
      glufosinate-tolerant GM cotton (Gossypium hirsutum L.) lines GHB119 and T304-40.
      These lines were compared with conventional varieties for growth habit,
      morphological characteristics, seed dormancy, and allelopathic activity
      associated with competitiveness and production of harmful substances. Outcrossing
      ability was not a concern due to the absence of sexually compatible wild
      relatives in Japan. Although slight statistical differences were observed between
      the GM line and its conventional comparator for some morphological
      characteristics, transgenes or transformation were not considered to be
      responsible for these differences. The trial demonstrated that competitiveness
      and production of harmful substances by these GM cotton lines were equivalent to
      conventional cotton varieties that have a long history of safe use, and no
      potential adverse effects to biosafety in Japan were observed.

PMID- 28510515
TI  - Biosimilars Ready, At Last, To Make Their Entrance: Stars Are Born or Do They
      Fizzle?
AB  - The future of biosimilars in this country is nothing if not uncertain. Most
      immediately, the U.S. Supreme Court is hearing a case that will determine the
      timing of the 180-day waiting period before a biosimilar can go on the market.
      But there are larger and longer-term issues at play as well.

PMID- 28510516
TI  - The Biosimilar Pipeline Seams Seem To Be Bursting.
AB  - The biosimilar segment of the pharmaceutical industry is on fire. Some 700
      biosimilars are at some stage of development, and more than 660 companies are
      involved in some way in the biosimilars land rush. Still, only a handful may get
      on the market in the next few years.

PMID- 28510513
TI  - Putative roles as oncogene or tumour suppressor of the Mid-clustered microRNAs in
      Gallid alphaherpesvirus 2 (GaHV2) induced Marek's disease lymphomagenesis.
AB  - In the last decade, numerous microRNAs (miRNAs) have been identified in diverse
      virus families, particularly in herpesviruses. Gallid alphaherpesvirus 2 (GaHV2)
      is a representative oncogenic alphaherpesvirus that induces rapid-onset T-cell
      lymphomas in its natural hosts, namely Marek's disease (MD). In the GaHV2 genome
      there are 26 mature miRNAs derived from 14 precursors assembled into three
      clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2
      miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been
      demonstrated to be critical in MD pathogenesis and/or tumorigenesis.
      Interestingly the downstream Mid-cluster is regulated and transcribed by the same
      promoter as the Meq-cluster in the latent phase of the infection, but the role of
      these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated
      the deletion mutants of the Mid-cluster and of its associated individual miRNAs
      in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid
      clustered miRNAs are not essential for virus replication. Using GaHV2-infected
      chickens as an animal model, we found that, compared with parental GX0101 virus,
      the individual deletion of miR-M31 decreased the mortality and gross tumour
      incidence of infected chickens while the deletion individually of miR-M1 or miR
      M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the
      deletion of the entire Mid-cluster region. More importantly, our data further
      confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral
      oncogene meq and suppresses its expression in GaHV2 infection. We report here
      that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially
      act either as oncogene or tumour suppressor in MD lymphomagenesis.

PMID- 28510517
TI  - Biosimilars in Oncology: Reality Could Bite the Copycats, Dog Potential Major
      Savings.
AB  - No one knows how much of an effect biosimilars will have on oncology
      expenditures. Pricing and market share are in a large, opaque "to be determined"
      cloud. But there's certainly potential for a major impact that could lower
      oncology expenditures by millions, if not billions.

PMID- 28510518
TI  - Biosimilar Makers Hope Court Starts 6-Month Wait Sooner.
AB  - The dispute centers on dueling interpretations of the Biologics Price Competition
      and Innovation Act, which says a company seeking to sell a biosimilar must give
      the maker of the brand-name biologic at least a 180-day notice before selling its
      drug.

PMID- 28510519
TI  - Health Insurers Often Foot Bill When Drug Coupons Are Used.
AB  - While coupons help individual consumers, they are also having a major impact on
      the insurance industry and anyone responsible for paying health care bills.
      Insurers and pharmacy benefit managers complain that they foil formularies and
      other pricing strategies designed to steer consumers to less-expensive drugs.

PMID- 28510520
TI  - Novel Devices for Delivering Diabetes Medications: Their Value and Some Coverage
      Considerations.
AB  - Insurers should consider covering new drug-delivery devices that can improve
      outcomes while lowering disease-specific pharmacy and long-term overall health
      care costs. Managing these devices in the pharmacy benefit will consolidate
      volume-based purchasing and capitalize on PBM strategies for improving adherence.

PMID- 28510521
TI  - A Seer of Trump's Coming Parses Repeal and Replace.
AB  - Diana Furchtgott-Roth, a senior fellow at the Manhattan Institute, a freemarket
      think tank, confidently predicted back in October what few people saw coming
      Donald Trump's electoral victory. Now she gives her take on the dismantling of
      the ACA and what might come after.

PMID- 28510522
TI  - Managed Care Reader Poll: Readers Believe Biosimilars Will Be Effective Against
      Costs.
AB  - In an online survey of readers conducted in late January and early February, 20%
      of the 113 respondents indicated that they believed that biosimilars will be
      highly effective in lowering drug costs, and the reader ratings of their
      effectiveness skewed toward positive.

PMID- 28510523
TI  - New Solutions for Curbing Runaway Drug Costs.
AB  - Long at odds, the interests of payers and providers are becoming more compatible
      and aligned. Both stakeholders need to collaborate to manage costs. Encouraging
      use of generics and biosimilars is one way they can slow down the soaring drug
      spend.

PMID- 28510524
TI  - Lost in Translation: Why patient-friendly communication strategies are more
      important than ever.
AB  - Efforts to improve patient communication must become a priority. Too often, the
      language we use in health care is a kind of code that serves billing and other
      purposes. Jargon may be an efficient and precise way for insiders to communicate,
      but it is impossible for patients to understand.

PMID- 28510525
TI  - $850 Per Bowel Movement?! Hard To Justify That Cost.
AB  - Constipation can be a serious and painful problem, and we shouldn't dismiss other
      people's suffering. On the other hand there's a danger when new medications are
      compared against placebo rather than against over-the-counter products with a
      history of effectiveness.

PMID- 28510526
TI  - With 'Repeal and Replace,' the Triple Aim Needed More Than Ever.
AB  - The Triple Aim hit a nerve with medical directors and health care managers of all
      kinds. That's because it is a concise way of summarizing the disparate issues
      that anyone trying to manage the delivery and cost of health care must deal with.

PMID- 28510527
TI  - The seesaw of CVD: Deaths down, costs up.
AB  - Coronary heart disease deaths will decline by 30% between 2010 and 2020 because
      of improvement in "cardiovascular health metrics" (avoidance of smoking, more
      physical activity, and so on). But this less-deadly era of CVD is going to be a
      more costly one, with direct medical costs of CVD more than doubling by 2030 to
      $918 billion from $396 billion in 2012.

PMID- 28510529
TI  - Perspectives.

PMID- 28510530
TI  - Effects of bulk and surface defects on the photocatalytic performance of size
      controlled TiO2 nanoparticles.
AB  - Defects are one of the crucial factors influencing the photocatalytic activities
      of TiO2 nanoparticles (NPs), as they directly affect the charge separation
      efficiencies. However, we found that the effect of bulk or surface defects on the
      photocatalytic performance of TiO2 is totally different. Here, we controllably
      synthesized four kinds of uniform TiO2 NPs, which were used to investigate how
      the bulk and surface defects influenced the photoactivities of samples with
      different particle sizes. Through XPS and EPR analysis, bulk and surface defects
      were observed in all the TiO2 samples and their amounts had been reduced after
      the calcination process. The reduction of bulk and surface defects enhanced the
      photoactivities of TiO2 NPs with diameters >10 nm, but the situation was inverse
      for those samples with diameters <10 nm. Therefore, we demonstrated that bulk
      defects play a dominate role in the change in photoactivity in particles larger
      than 10 nm, while surface defects are more important than bulk defects for
      particles less than 10 nm.

PMID- 28510531
TI  - Oriented epitaxial TiO2 nanowires for water splitting.
AB  - Highly oriented epitaxial rutile titanium dioxide (TiO2) nanowire arrays have
      been hydrothermally grown on polycrystalline TiO2 templates with their
      orientation dependent on the underlying TiO2 grain. Both the diameter and areal
      density of the nanowires were tuned by controlling the precursor concentration,
      and the template surface energy and roughness. Nanowire tip sharpness was
      influenced by precursor solubility and diffusivity. A new secondary ion mass
      spectrometer technique has been developed to install additional nucleation sites
      in single crystal TiO2 templates and the effect on nanowire growth was probed.
      Using the acquired TiO2 nanowire synthesis knowhow, an assortment of nanowire
      arrays were installed upon the surface of undoped TiO2 photo-electrodes and
      assessed for their photo-electrochemical water splitting performance. The key
      result obtained was that the presence of short and dispersed nanowire arrays
      significantly improved the photocurrent when the illumination intensity was
      increased from 100 to 200 mW cm-2. This is attributed to the alignment of the
      homoepitaxially grown nanowires to the [001] direction, which provides the
      fastest charge transport in TiO2 and an improved pathway for photo-holes to find
      water molecules and undertake oxidation. This result lays a foundation for
      achieving efficient water splitting under conditions of concentrated solar
      illumination.

PMID- 28510532
TI  - Scattering and plasmonic synergetic enhancement of the performance of dye
      sensitized solar cells by double-shell SiO2@Au@TiO2 microspheres.
AB  - The Au nanoparticle sandwich double spheric-shells of SiO2@Au@TiO2 (SAT)
      microspheres are synthesized. The significant influence of the SAT microspheres
      on the properties of dye-sensitized solar cells (DSSCs) is investigated. Studies
      indicate that the introduction of SAT markedly enhanced the light scattering and
      capture ability of DSSCs and thus photogenerated electrons. DSSCs doped with 2.25
      wt% SAT exhibit a maximum short circuit current density of 17.0 mA cm-2 and
      photoelectric conversion efficiency of 7.14%, which are remarkably higher than
      those of conventional DSSCs at 15.7% and 21.2%, respectively. The marked
      enhancement in the performance of the optimal DSSCs can be attributed to the
      synergetic complementary effect of the enhanced light scattering of the
      microspheres and to the localized surface plasmon resonance of the Au
      nanoparticles in the SAT, and is a novel promising way of enhancing the
      performance of DSSCs.

PMID- 28510533
TI  - Coordination polymer nanocapsules prepared using metal-organic framework
      templates for pH-responsive drug delivery.
AB  - A facile, efficient, and versatile approach is presented to synthesize pH
      responsive nanocapsules (~120 nm) by combining the advantages of metal-organic
      frameworks (MOFs) and metal-organic thin films. ZIF-8 nanoparticles are used as
      templates on which a thin film coating of iron(III)-catechol complexes is derived
      from the coordination between dopamine-modified alginate (AlgDA) and iron(III)
      ions. After the template removal, nanocapsules with a pH-responsive wall are
      obtained. Doxorubicin (Dox), a typical anticancer drug, is first immobilized in
      ZIF-8 frameworks through coprecipitation and then encapsulated in nanocapsules
      after the removal of ZIF-8. The structure of the iron(III)-catechol complex
      varies with pH value, thus conferring the Dox@Nanocapsules with tailored release
      behavior in vitro. Cytotoxicity tests illustrate the highly effective
      cytotoxicity of Dox@Nanocapsules towards cancer cells. This study provides a new
      method for preparing smart nanocapsules and offers more opportunities for the
      controlled delivery of drugs.

PMID- 28510528
TI  - Identification of octopaminergic neurons that modulate sleep suppression by male
      sex drive.
AB  - Molecular and circuit mechanisms for balancing competing drives are not well
      understood. While circadian and homeostatic mechanisms generally ensure
      sufficient sleep at night, other pressing needs can overcome sleep drive. Here,
      we demonstrate that the balance between sleep and sex drives determines whether
      male flies sleep or court, and identify a subset of octopaminergic neurons (MS1)
      that regulate sleep specifically in males. When MS1 neurons are activated,
      isolated males sleep less, and when MS1 neurons are silenced, the normal male
      sleep suppression in female presence is attenuated and mating behavior is
      impaired. MS1 neurons do not express the sexually dimorphic FRUITLESS (FRU)
      transcription factor, but form male-specific contacts with FRU-expressing
      neurons; calcium imaging experiments reveal bidirectional functional connectivity
      between MS1 and FRU neurons. We propose octopaminergic MS1 neurons interact with
      the FRU network to mediate sleep suppression by male sex drive.

PMID- 28510534
TI  - Three fundamental devices in one: a reconfigurable multifunctional device in two
      dimensional WSe2.
AB  - The three pillars of semiconductor device technologies are (1) the p-n diode, (2)
      the metal-oxide-semiconductor field-effect transistor and (3) the bipolar
      junction transistor. They have enabled the unprecedented growth in the field of
      information technology that we see today. Until recently, the technological
      revolution for better, faster and more efficient devices has been governed by
      scaling down the device dimensions following Moore's Law. With the slowing of
      Moore's law, there is a need for alternative materials and computing technologies
      that can continue the advancement in functionality. Here, we describe a single,
      dynamically reconfigurable device that implements these three fundamental device
      functions. The device uses buried gates to achieve n- and p-channels and fits
      into a larger effort to develop devices with enhanced functionalities, including
      logic functions, over device scaling. As they are all surface conducting devices,
      we use one material parameter, the interface trap density of states, to describe
      the key figure-of-merit of each device.

PMID- 28510535
TI  - Ultrafast magnetization dynamics in Nickel: impact of pump photon energy.
AB  - Magnetization dynamics on a femtosecond timescale has been observed for a huge
      variety of magnetic structures. However, the influence of different excitation
      photon energies has not been studied in detail yet. In our time-resolved magneto
      optical Kerr effect setup we excite a Nickel bulk system with 1.55 and 3.1 eV,
      respectively, leading to different remagnetization dynamics depending on the
      chosen photon energy. Furthermore we complement our experimental data with a
      theoretical approach applying appropriate Boltzmann collision integrals including
      the density of states of Nickel. The comparison between the experimental data and
      the theoretical approach indicates that photon-energy dependent transport
      processes play a major role in this setup.

PMID- 28510536
TI  - Effect of nanostructures orientation on electroosmotic flow in a microfluidic
      channel.
AB  - Electroosmotic flow (EOF) is an electric-field-induced fluid flow that has
      numerous micro-/nanofluidic applications, ranging from pumping to chemical and
      biomedical analyses. Nanoscale networks/structures are often integrated in
      microchannels for a broad range of applications, such as electrophoretic
      separation of biomolecules, high reaction efficiency catalytic microreactors, and
      enhancement of heat transfer and sensing. Their introduction has been known to
      reduce EOF. Hitherto, a proper study on the effect of nanostructures orientation
      on EOF in a microfluidic channel is yet to be carried out. In this investigation,
      we present a novel fabrication method for nanostructure designs that possess
      maximum orientation difference, i.e. parallel versus perpendicular indented
      nanolines, to examine the effect of nanostructures orientation on EOF. It
      consists of four phases: fabrication of silicon master, creation of mold insert
      via electroplating, injection molding with cyclic olefin copolymer, and thermal
      bonding and integration of practical inlet/outlet ports. The effect of
      nanostructures orientation on EOF was studied experimentally by current
      monitoring method. The experimental results show that nanolines which are
      perpendicular to the microchannel reduce the EOF velocity significantly
      (approximately 20%). This flow velocity reduction is due to the distortion of
      local electric field by the perpendicular nanolines at the nanostructured surface
      as demonstrated by finite element simulation. In contrast, nanolines which are
      parallel to the microchannel have no effect on EOF, as it can be deduced that the
      parallel nanolines do not distort the local electric field. The outcomes of this
      investigation contribute to the precise control of EOF in lab-on-chip devices,
      and fundamental understanding of EOF in devices which utilize nanostructured
      surfaces for chemical and biological analyses.

PMID- 28510537
TI  - Converging evolution leads to near maximal junction diversity through parallel
      mechanisms in B and T cell receptors.
AB  - T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3)
      genetic diversity is produced through multiple diversification and selection
      stages. Potential holes in the CDR3 repertoire were argued to be linked to
      immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no
      Dbeta germline genetic diversity, and the question emerges as to whether they can
      produce a diverse CDR3 repertoire. In order to address the genetic diversity of
      the adaptive immune system, appropriate quantitative measures for diversity and
      large-scale sequencing are required. Such a diversity method should incorporate
      the complex diversification mechanisms of the adaptive immune response and the
      BCR and TCR loci structure. We combined large-scale sequencing and diversity
      measures to show that TCRs have a near maximal CDR3 genetic diversity.
      Specifically, TCR have a larger junctional and V germline diversity, which starts
      more 5' in Vbeta than BCRs. Selection decreases the TCR repertoire diversity, but
      does not affect BCR repertoire. As a result, TCR is as diverse as BCR repertoire,
      with a biased CDR3 length toward short TCRs and long BCRs. These differences
      suggest parallel converging evolutionary tracks to reach the required diversity
      to avoid holes in the CDR3 repertoire.

PMID- 28510538
TI  - Measuring and assessing individual external doses during the rehabilitation phase
      in Iitate village after the Fukushima Daiichi nuclear power plant accident.
AB  - After the Fukushima Daiichi nuclear power plant accident in 2011, Iitate village
      was placed under an evacuation order because the level of radioactive materials
      drifting from the nuclear plant to the village was above a government-set level
      for allowing residents to live in the area. The evacuation advisory for most of
      the village was lifted on 31 March 2017. For displaced residents deciding whether
      or not to return to their homes, it is important to correctly understand and
      estimate the realistic individual external doses they will receive after
      returning to the village. In this study, with the support of residents of the
      village, we used a personal dosimeter (D-Shuttle) coupled with a global
      positioning system device to measure and thus understand realistic individual
      external doses while the residents were in Iitate village and to project the
      individual external doses for different administrative districts as of 1 April
      2017. The measured individual external doses measured by D-Shuttle for 38 study
      participants showed that the doses measured during time spent inside the village
      were higher and more widely distributed than the doses measured during time spent
      outside the village. The exposure ratio (ER) was defined as the ratio of
      additional individual external dose measured by D-Shuttle to the additional
      ambient dose based on an airborne monitoring survey. The medians of the average
      ERs were 0.13 (min-max 0.06-0.27) for time spent at home and 0.18 (min-max 0.08
      0.36) for time spent outdoors. Projected additional annual individual external
      doses as of 1 April 2017 for different administrative districts in the village
      were calculated using ERs obtained in this study. Assuming that individuals spent
      8 h per day on outdoor activities and 16 h on indoor activities, additional
      annual individual external doses were estimated to be below 3 mSv using the mean
      of the average ERs for most districts in the village, and these values were well
      below the individual external doses estimated using the approach taken by the
      central government. The results of this study provide valuable information both
      for understanding realistic radiological situations in the village and for those
      who want to know their future individual external dose in order to make a
      decision on whether or not to live in the village.

PMID- 28510539
TI  - Statistical physics approaches to subnetwork dynamics in biochemical systems.
AB  - We apply a Gaussian variational approximation to model reduction in large
      biochemical networks of unary and binary reactions. We focus on a small subset of
      variables (subnetwork) of interest, e.g. because they are accessible
      experimentally, embedded in a larger network (bulk). The key goal is to write
      dynamical equations reduced to the subnetwork but still retaining the effects of
      the bulk. As a result, the subnetwork-reduced dynamics contains a memory term and
      an extrinsic noise term with non-trivial temporal correlations. We first derive
      expressions for this memory and noise in the linearized (Gaussian) dynamics and
      then use a perturbative power expansion to obtain first order nonlinear
      corrections. For the case of vanishing intrinsic noise, our description is
      explicitly shown to be equivalent to projection methods up to quadratic terms,
      but it is applicable also in the presence of stochastic fluctuations in the
      original dynamics. An example from the epidermal growth factor receptor
      signalling pathway is provided to probe the increased prediction accuracy and
      computational efficiency of our method.

PMID- 28510541
TI  - Quick Hits.

PMID- 28510542
TI  - From Science to Knowledge to Hope.

PMID- 28510540
TI  - Diagnosis of Congenital Coarctation of the Aorta and Accompany Malformations in
      Infants by Multi-Detector Computed Tomography Angiography and Transthoracic
      Echocardiography: A Chinese Clinical Study.
AB  - BACKGROUND The purpose of this study was to evaluate the utility of multi
      detector computed tomography (MDCT) angiography and transthoracic
      echocardiography (TTE) in the diagnosis of congenital coarctation of the aorta
      (CoA) and accompanying malformations in infants. MATERIAL AND METHODS From
      January 2012 and December 2015, we enrolled 68 infants with clinically suspected
      CoA who underwent MDCT angiography and TTE in our hospital. Surgical correction
      was conducted to confirm the diagnostic accuracy of both examinations in all
      patients. RESULTS In this study, the diagnosis of CoA was confirmed infants by
      surgical results in 55 of 68 infants. The diagnostic accuracy, sensitivity, and
      specificity of MDCT angiography were 95.6%, 96.4%, and 92.3%, respectively. The
      diagnostic accuracy, sensitivity, and specificity of TTE were 88.2%, 90.9%, and
      76.9%, respectively. There was no significant difference in diagnostic accuracy,
      sensitivity, and specificity between MDCT angiography and TTE (chi2=2.473,
      p>0.05, chi2=1.373, p>0.05 and chi2=1.182, p>0.05, respectively). In the
      diagnosis of concomitant cardiac abnormalities with CoA, the 2 methods also play
      different roles. CONCLUSIONS MDCT angiography and TTE play different roles in the
      diagnosis of CoA and accompany malformations. MDCT angiography in the diagnosis
      of the extra-cardiac vascular malformations is better than TTE, and TTE is
      superior to MDCT angiography in diagnosing intracardiac malformation. Combined
      MDCT angiography and TTE is a relatively valuable, reliable, and noninvasive
      method in the diagnosis of CoA and accompany malformations in infants.

PMID- 28510543
TI  - Missing Link.

PMID- 28510544
TI  - Science without Walls.

PMID- 28510545
TI  - Food Fright!

PMID- 28510546
TI  - Polar Ice Squad.

PMID- 28510547
TI  - Greenland's Vanished Vikings.

PMID- 28510548
TI  - Revenge of the Super Lice.

PMID- 28510550
TI  - Romance of the Vanished Past.

PMID- 28510549
TI  - The Quantum Multiverse.

PMID- 28510551
TI  - The Meaning of Lichen.

PMID- 28510553
TI  - Space Age Firefighters.

PMID- 28510552
TI  - Print, Wipe, Rewrite.

PMID- 28510554
TI  - Knowledge Is Infrastructure.

PMID- 28510556
TI  - Making AI More Human.

PMID- 28510555
TI  - The iOS 11 To-Do List.

PMID- 28510557
TI  - Letters.

PMID- 28510558
TI  - Sounds Like Trouble.

PMID- 28510559
TI  - Unlocking the Mystery of ALS.

PMID- 28510560
TI  - 50, 100 &150 Years Ago.

PMID- 28510561
TI  - The Messy Truth about Weight Loss.

PMID- 28510562
TI  - Menstrual Cycle "on a Chip".

PMID- 28510563
TI  - Probing for Parkinson's.

PMID- 28510564
TI  - Robo Pizzaiolo.

PMID- 28510565
TI  - Electric Renaissance.

PMID- 28510566
TI  - Radiation Triage.

PMID- 28510567
TI  - Recommended.

PMID- 28510568
TI  - Swell or High Water.

PMID- 28510569
TI  - Lost at Sea.

PMID- 28510570
TI  - BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with
      meta-analyses.
AB  - BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is
      overexpressed in breast cancer and has been incorporated in the oncotype DX and
      PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as
      multiple protein isoforms that interact with diverse partners, including
      chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell
      survival. The BAG-1L isoform specifically binds to and increases the
      transcriptional activity of oestrogen receptor in cells, and in some, but not all
      studies, BAG-1 expression is predictive of clinical outcome in breast cancer.
      METHODS: A systematic review of published studies reporting BAG-1 (mRNA and/or
      protein) expression and clinical outcome in early breast cancer. The REporting
      Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were
      used as a template against which data were assessed. Meta-analyses were performed
      for studies that provided a hazard ratio and 95% confidence intervals for
      clinical outcomes including disease-free survival or breast cancer-specific
      survival from univariate analysis. RESULTS: Eighteen studies used differing
      methodologies and reported on differing outcomes. Meta-analyses were only
      possible on results from a subset of reported studies. Meta-analyses suggested
      improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by
      immunohistochemisty. CONCLUSIONS: Increased levels of BAG-1 are associated with
      better breast cancer outcomes.

PMID- 28510572
TI  - 1.2 million kids and counting-Mobile science laboratories drive student interest
      in STEM.
AB  - In today's increasingly technological society, a workforce proficient in science,
      technology, engineering, and mathematics (STEM) skills is essential. Research has
      shown that active engagement by K-12 students in hands-on science activities that
      use authentic science tools promotes student learning and retention. Mobile
      laboratory programs provide this type of learning in schools and communities
      across the United States and internationally. Many programs are members of the
      Mobile Lab Coalition (MLC), a nonprofit organization of mobile and other
      laboratory-based education programs built on scientist and educator
      collaborations. A recent survey of the member programs revealed that they provide
      an impressive variety of programming and have collectively served over 1.2
      million students across the US.

PMID- 28510571
TI  - Second-line pazopanib in patients with relapsed and refractory small-cell lung
      cancer: a multicentre phase II study of the Hellenic Oncology Research Group.
AB  - BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic
      activity. Vascular endothelial growth factor expression is increased in SCLC and
      is correlated with poor prognosis. The efficacy and tolerance of second-line
      pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum
      sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were
      enrolled in a multicentre phase II study. The primary end point was the
      progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800
      mg per day per os) was administered until progressive disease (PD). Circulating
      tumour cells (CTCs) were enumerated using the Cellsearch assay. RESULTS: All
      patients were evaluable for response and toxicity. In the intention-to-treat
      analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence
      interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD.
      Accrual in cohort B was halted because the hard-stop rule was met; in cohort A,
      the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients
      received pazopanib for >6 months and 3 of them for >12 months. One pazopanib
      cycle resulted to a significant decrease to the number of patients with ?5
      CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS
      for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI:
      3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No
      unexpected toxicity was observed. CONCLUSIONS: Second-line treatment with
      pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising
      objective responses and disease control; CTC enumeration might serve as a
      reliable surrogate biomarker of response.

PMID- 28510573
TI  - Comparison of artemether-lumefantrine and chloroquine with and without primaquine
      for the treatment of Plasmodium vivax infection in Ethiopia: A randomized
      controlled trial.
AB  - BACKGROUND: Recent efforts in malaria control have resulted in great gains in
      reducing the burden of Plasmodium falciparum, but P. vivax has been more
      refractory. Its ability to form dormant liver stages confounds control and
      elimination efforts. To compare the efficacy and safety of primaquine regimens
      for radical cure, we undertook a randomized controlled trial in Ethiopia. METHODS
      AND FINDINGS: Patients with normal glucose-6-phosphate dehydrogenase status with
      symptomatic P. vivax mono-infection were enrolled and randomly assigned to
      receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in
      combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A
      total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in
      the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent
      episodes were treated with the same treatment allocated at enrolment. The primary
      endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk
      of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ
      treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0%
      (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following
      AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI
      0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI
      2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk
      of recurrence by day 42 appeared greater following AL treatment than CQ treatment
      (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence
      rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ
      compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9
      9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ
      (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the
      occurrence of adverse events between treatment arms. The main limitations of the
      study were the early termination of the trial and the omission of haemoglobin
      measurement after day 42, resulting in an inability to estimate the cumulative
      risk of anaemia. CONCLUSIONS: Despite evidence of CQ-resistant P. vivax, the risk
      of recurrence in this study was greater following treatment with AL unless it was
      combined with a supervised course of PQ. PQ combined with either CQ or AL was
      well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01680406.

PMID- 28510574
TI  - Dose of antivenom for the treatment of snakebite with neurotoxic envenoming:
      Evidence from a randomised controlled trial in Nepal.
AB  - BACKGROUND: Currently, there is inadequate evidence on which to base clinical
      management of neurotoxic snakebite envenoming, especially in the choice of
      initial antivenom dosage. This randomised controlled trial compared the
      effectiveness and safety of high versus low initial antivenom dosage in victims
      of neurotoxic envenoming. METHODOLOGY/ PRINCIPAL FINDINGS: This was a balanced,
      randomised, double-blind trial that was conducted in three health care centers
      located in the Terai plains of Nepal. Participants received either low (two
      vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The
      primary composite outcome consisted of death, the need for assisted ventilation
      and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom
      treatment. Between April 2011 and October 2012, 157 snakebite victims were
      enrolled, of which 154 were analysed (76 in the low and 78 in the high initial
      dose group). Sixty-seven (43.5%) participants met the primary outcome definition.
      The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%)
      initial dose group (difference = 10.2%, 95%CI [-6.7 to 27.1], p = 0.264). The
      mean number of vials used was similar between treatment groups. Overall, patients
      bitten by kraits did worse than those bitten by cobras. The occurrence of
      treatment-related adverse events did not differ among treatment groups. A total
      of 19 serious adverse events occurred, including seven attributed to antivenom.
      CONCLUSIONS: This first robust trial investigating antivenom dosage for
      neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal
      performs poorly. Although the high initial dose regimen is not more effective
      than the low initial dose, it offers the practical advantage of being a single
      dose, while not incurring higher consumption or enhanced risk of adverse
      reaction. The development of new and more effective antivenoms that better target
      the species responsible for bites in the region will help improve future
      patients' outcomes. TRIAL REGISTRATION: The study was registered on
      clinicaltrials.gov (NCT01284855) (GJ 5/1).

PMID- 28510575
TI  - Electro-mechanical dynamics of spiral waves in a discrete 2D model of human
      atrial tissue.
AB  - We investigate the effect of mechano-electrical feedback and atrial fibrillation
      induced electrical remodelling (AFER) of cellular ion channel properties on the
      dynamics of spiral waves in a discrete 2D model of human atrial tissue. The
      tissue electro-mechanics are modelled using the discrete element method (DEM).
      Millions of bonded DEM particles form a network of coupled atrial cells
      representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of
      electrical excitation waves and mechanical contraction in the tissue. In the
      tissue model, each cell is modelled by nine particles, accounting for the
      features of individual cellular geometry; and discrete inter-cellular spatial
      arrangement of cells is also considered. The electro-mechanical model of a human
      atrial single-cell was constructed by strongly coupling the electrophysiological
      model of Colman et al. to the mechanical myofilament model of Rice et al., with
      parameters modified based on experimental data. A stretch-activated channel was
      incorporated into the model to simulate the mechano-electrical feedback. In order
      to investigate the effect of mechano-electrical feedback on the dynamics of
      spiral waves, simulations of spiral waves were conducted in both the
      electromechanical model and the electrical-only model in normal and AFER
      conditions, to allow direct comparison of the results between the models.
      Dynamics of spiral waves were characterized by tracing their tip trajectories,
      stability, excitation frequencies and meandering range of tip trajectories. It
      was shown that the developed DEM method provides a stable and efficient model of
      human atrial tissue with considerations of the intrinsically discrete and
      anisotropic properties of the atrial tissue, which are challenges to handle in
      traditional continuum mechanics models. This study provides mechanistic insights
      into the complex behaviours of spiral waves and the genesis of atrial
      fibrillation by showing an important role of the mechano-electrical feedback in
      facilitating and promoting atrial fibrillation.

PMID- 28510576
TI  - Comparison of peripapillary choroidal thickness between healthy subjects and
      patients with Parkinson's disease.
AB  - PURPOSE: To study peripapillary choroidal thickness (PPCT) in healthy subjects
      using swept-source optical coherence tomography (SS-OCT), and to evaluate PPCT
      differences between Parkinson's disease (PD) patients, and age- and sex-matched
      healthy controls. DESIGN: Case-control study. METHODS: 80 healthy subjects and 40
      PD patients were consecutively recruited in this single institution study. The
      healthy subjects were divided into two populations: a teaching population (n =
      40, used to establish choroidal zones) and a validating population (n = 40, used
      to compare measurements with PD patients). An optic disc 6.0*6.0 mm three
      dimensional scan was obtained using Deep Range Imaging (DRI) OCT Triton. A 26*26
      cube-grid centered on the optic disc was generated to automatically measure
      choroidal thickness. Five concentric choroidal zones were established and used to
      compare PPCT between healthy and PD patients. RESULTS: PPCT was significantly
      thicker in PD patients compared with controls in all four concentric zones
      evaluated (p<=0.0001). PPCT followed a similar pattern in controls and PD; it was
      thicker in the temporosuperior region, followed by the superior, temporal, nasal,
      and inferior regions. CONCLUSION: PD patients presented with an increased PPCT in
      all zones surrounding the optic disc compared with healthy subjects. The
      peripapillary choroidal tissue showed a concentric pattern, with the thickness
      increasing with increasing distance from the optic nerve. SS-OCT could be useful
      for evaluating choroidal thinning in clinical practice.

PMID- 28510577
TI  - Are horses capable of mirror self-recognition? A pilot study.
AB  - Mirror Self-Recognition (MSR) unveils complex cognitive, social and emotional
      skills and it has been found only in humans and few other species, such as great
      apes, dolphins, elephants and magpies. In this pilot study, we tested if horses
      show the capacity of MSR. Four subjects living socially under naturalistic
      conditions were selected for the experiment. We adopted the classical mark test,
      which consists in placing a coloured mark on an out-of-view body part, visible
      only through mirror inspection. If the animal considers the image as its own, it
      will use its reflection to detect the mark and will try to explore it. We
      enhanced the classical paradigm by introducing a double-check control. Only in
      the presence of the reflecting surface, animals performed tactile and olfactory
      exploration of the mirror and looked behind it. These behaviors suggest that
      subjects were trying to associate multiple sensory cues (visual, tactile and
      olfactory) to the image in the mirror. The lack of correspondence between the
      collected stimuli in front of the mirror and the response to the colored mark
      lead us to affirm that horses are able to perceive that the reflected image is
      incongruent when compared with the memorized information of a real horse.
      However, without replication of data, the self-directed behavior towards the
      colored marks showed by our horses cannot be sufficient per se to affirm that
      horses are capable of self-recognition.

PMID- 28510578
TI  - Neurofeedback as a form of cognitive rehabilitation therapy following stroke: A
      systematic review.
AB  - Neurofeedback therapy (NFT) has been used within a number of populations however
      it has not been applied or thoroughly examined as a form of cognitive
      rehabilitation within a stroke population. Objectives for this systematic review
      included: i) identifying how NFT is utilized to treat cognitive deficits
      following stroke, ii) examining the strength and quality of evidence to support
      the use of NFT as a form of cognitive rehabilitation therapy (CRT) and iii)
      providing recommendations for future investigations. Searches were conducted
      using OVID (Medline, Health Star, Embase + Embase Classic) and PubMed databases.
      Additional searches were completed using the Cochrane Reviews library database,
      Google Scholar, the University of Toronto online library catalogue,
      ClinicalTrials.gov website and select journals. Searches were completed Feb/March
      2015 and updated in June/July/Aug 2015. Eight studies were eligible for inclusion
      in this review. Studies were eligible for inclusion if they: i) were specific to
      a stroke population, ii) delivered CRT via a NFT protocol, iii) included
      participants who were affected by a cognitive deficit(s) following stroke (i.e.
      memory loss, loss of executive function, speech impairment etc.). NFT protocols
      were highly specific and varied within each study. The majority of studies
      identified improvements in participant cognitive deficits following the
      initiation of therapy. Reviewers assessed study quality using the Downs and Black
      Checklist for Measuring Study Quality tool; limited study quality and strength of
      evidence restricted generalizability of conclusions regarding the use of this
      therapy to the greater stroke population. Progression in this field requires
      further inquiry to strengthen methodology quality and study design. Future
      investigations should aim to standardize NFT protocols in an effort to understand
      the dose-response relationship between NFT and improvements in functional
      outcome. Future investigations should also place a large emphasis on long-term
      participant follow-up.

PMID- 28510582
TI  - The worst case scenario: Locomotor and collision demands of the longest periods
      of gameplay in professional rugby union.
AB  - A number of studies have used global positioning systems (GPS) to report on
      positional differences in the physical game demands of rugby union both on an
      average and singular bout basis. However, the ability of these studies to report
      quantitative data is limited by a lack of validation of certain aspects of
      measurement by GPS micro-technology. Furthermore no study has analyzed the
      positional physical demands of the longest bouts of ball-in-play time in rugby
      union. The aim of the present study is to compare the demands of the single
      longest period of ball-in-play, termed "worst case scenario" (WCS) between
      positional groups, which have previously been reported to have distinguishable
      game demands. The results of this study indicate that WCS periods follow a
      similar sporadic pattern as average demands but are played at a far higher pace
      than previously reported for average game demands with average meters per minute
      of 116.8 m. The positional differences in running and collision activity
      previously reported are perpetuated within WCS periods. Backs covered greater
      total distances than forwards (318 m vs 289 m), carried out more high-speed
      running (11.1 m.min-1 vs 5.5 m.min-1) and achieved higher maximum velocities
      (MaxVel). Outside Backs achieved the highest MaxVel values (6.84 m.sec-1). Tight
      Five and Back Row forwards underwent significantly more collisions than Inside
      Back and Outside Backs (0.73 & 0.89 collisions.min-1 vs 0.28 & 0.41
      collisions.min-1 respectively). The results of the present study provide
      information on the positional physical requirements of performance in prolonged
      periods involving multiple high intensity bursts of effort. Although the current
      state of GPS micro-technology as a measurement tool does not permit reporting of
      collision intensity or acceleration data, the combined use of video and GPS
      provides valuable information to the practitioner. This can be used to match and
      replicate game demands in training.

PMID- 28510579
TI  - Socio-economic status over the life course and obesity: Systematic review and
      meta-analysis.
AB  - BACKGROUND: The purpose of this review was to summarize the published literature
      on the association of childhood, adulthood and life course socio-economic status
      (SES) with obesity between January 1990 and June 2015. METHODS: The major medical
      electronic databases were searched to identify studies that examined SES over the
      life-course in relation to obesity. A total of 219 studies were identified
      through the initial search, and 35 qualified for full review. Of these, 14
      publications met our inclusion criteria for the meta-analysis, all from developed
      or upper-middle income countries. RESULTS: There was a consistent association
      between lower life course SES and obesity among women (summary OR: 1.35, 95% CI:
      1.04, 1.76), but not among men (summary OR: 0.92, 95% CI: 0.60, 1.40). Overall,
      mean BMI was higher among individuals with lower life course SES compared with
      those with higher life course SES (summary mean BMI difference: 0.65, 95% CI:
      0.59, 0.71). Mean waist circumference (WC) was higher among women with lower life
      course SES compared with those with higher life course SES (summary mean WC:
      4.67, 95% CI: 4.15, 5.20), but lower among men (summary mean WC difference: 
      0.10, 95% CI: -0.11, -0.08). CONCLUSION: The inverse relationship between life
      course SES and obesity among women was consistent, based mostly on studies in
      developed countries. Nevertheless, critical information gaps remain in relation
      to the impact of childhood and life course SES on obesity in developing
      countries.

PMID- 28510580
TI  - Disease-associated mitochondrial mutations and the evolution of primate
      mitogenomes.
AB  - Several human diseases have been associated with mutations in mitochondrial genes
      comprising a set of confirmed and reported mutations according to the MITOMAP
      database. An analysis of complete mitogenomes across 139 primate species showed
      that most confirmed disease-associated mutations occurred in aligned codon
      positions and gene regions under strong purifying selection resulting in a strong
      evolutionary conservation. Only two confirmed variants (7.1%), coding for the
      same amino acids accounting for severe human diseases, were identified without
      apparent pathogenicity in non-human primates, like the closely related Bornean
      orangutan. Conversely, reported disease-associated mutations were not especially
      concentrated in conserved codon positions, and a large fraction of them occurred
      in highly variable ones. Additionally, 88 (45.8%) of reported mutations showed
      similar variants in several non-human primates and some of them have been present
      in extinct species of the genus Homo. Considering that recurrent mutations
      leading to persistent variants throughout the evolutionary diversification of
      primates are less likely to be severely damaging to fitness, we suggest that
      these 88 mutations are less likely to be pathogenic. Conversely, 69 (35.9%) of
      reported disease-associated mutations occurred in extremely conserved aligned
      codon positions which makes them more likely to damage the primate mitochondrial
      physiology.

PMID- 28510583
TI  - Liver fibrosis staging with a new 2D-shear wave elastography using comb-push
      technique: Applicability, reproducibility, and diagnostic performance.
AB  - OBJECTIVE: To evaluate the applicability, reproducibility, and diagnostic
      performance of a new 2D-shear wave elastography (SWE) using the comb-push
      technique (2D CP-SWE) for detection of hepatic fibrosis, using histopathology as
      the reference standard. MATERIALS AND METHODS: This prospective study was
      approved by the institutional review board, and informed consent was obtained
      from all patients. The liver stiffness (LS) measurements were obtained from 140
      patients, using the new 2D-SWE, which uses comb-push excitation to produce shear
      waves and a time-aligned sequential tracking method to detect shear wave signals.
      The applicability rate of 2D CP-SWE was estimated, and factors associated with
      its applicability were identified. Intraobserver reproducibility was evaluated in
      the 105 patients with histopathologic diagnosis, and interobserver
      reproducibility was assessed in 20 patients. Diagnostic performance of the 2D CP
      SWE for hepatic fibrosis was evaluated by receiver operating characteristic (ROC)
      curve analysis. RESULTS: The applicability rate of 2D CP-SWE was 90.8% (109 of
      120). There was a significant difference in age, presence or absence of ascites,
      and the distance from the transducer to the Glisson capsule between the patients
      with applicable LS measurements and patients with unreliable measurement or
      technical failure. The intraclass correlation of interobserver agreement was
      0.87, and the value for the intraobserver agreement was 0.95. The area under the
      ROC curve of LS values for stage F2 fibrosis or greater, stage F3 or greater, and
      stage F4 fibrosis was 0.874 (95% confidence interval [CI]: 0.794-0.930), 0.905
      (95% CI: 0.832-0.954), and 0.894 (95% CI: 0.819-0.946), respectively. CONCLUSION:
      2D CP-SWE can be employed as a reliable method for assessing hepatic fibrosis
      with a reasonably good diagnostic performance, and its applicability might be
      influenced by age, ascites, and the distance between the transducer and Glisson
      capsule.

PMID- 28510581
TI  - Association between the hyperuricemia and nonalcoholic fatty liver disease risk
      in a Chinese population: A retrospective cohort study.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease associated
      with high levels of serum uric acid (SUA). However, whether this relationship
      applies in obese subjects has been unclear, and no cohort study has previously
      been conducted in non-obese subjects. We therefore performed a retrospective
      cohort study among employees of seven companies in China to investigate whether
      hyperuricemia was independently associated with NAFLD in obese and non-obese
      subjects, respectively. A total of 2383 initially NAFLD-free subjects were
      followed up for four years, and 15.2% (363/2383) developed NAFLD. Hyperuricemia
      subjects had a higher cumulative incidence than did those with normouricemia
      (29.0% vs. 12.9%, P<0.001). Cox proportional hazard regression analyses showed
      that baseline hyperuricemia was significantly associated with risk of developing
      NAFLD in non-obese subjects. This relationship was significantly independent of
      baseline age, gender, metabolic syndrome components, and other clinical variables
      (RR = 1.389, 95%CI: 1.051-2.099). However, this association did not exist in
      obese subjects (RR = 1.010, 95%CI: 0.649-1.571). The independent effect of
      hyperuricemia on NAFLD was stronger in females (RR = 2.138, 95%CI: 1.050-4.355)
      than in males (RR = 1.435, 95%CI: 1.021-2.018). In conclusion, further studies
      are needed to explore the different mechanisms between obese and non-obese
      subjects, and the reason hyperuricemia raises NAFLD risk in females more than in
      males.

PMID- 28510584
TI  - Identification of novel risk factors for community-acquired Clostridium difficile
      infection using spatial statistics and geographic information system analyses.
AB  - BACKGROUND: The rate of community-acquired Clostridium difficile infection (CA
      CDI) is increasing. While receipt of antibiotics remains an important risk factor
      for CDI, studies related to acquisition of C. difficile outside of hospitals are
      lacking. As a result, risk factors for exposure to C. difficile in community
      settings have been inadequately studied. MAIN OBJECTIVE: To identify novel
      environmental risk factors for CA-CDI. METHODS: We performed a population-based
      retrospective cohort study of patients with CA-CDI from 1/1/2007 through
      12/31/2014 in a 10-county area in central North Carolina. 360 Census Tracts in
      these 10 counties were used as the demographic Geographic Information System
      (GIS) base-map. Longitude and latitude (X, Y) coordinates were generated from
      patient home addresses and overlaid to Census Tracts polygons using ArcGIS;
      ArcView was used to assess "hot-spots" or clusters of CA-CDI. We then constructed
      a mixed hierarchical model to identify environmental variables independently
      associated with increased rates of CA-CDI. RESULTS: A total of 1,895 unique
      patients met our criteria for CA-CDI. The mean patient age was 54.5 years; 62%
      were female and 70% were Caucasian. 402 (21%) patient addresses were located in
      "hot spots" or clusters of CA-CDI (p<0.001). "Hot spot" census tracts were
      scattered throughout the 10 counties. After adjusting for clustering and
      population density, age >= 60 years (p = 0.03), race (<0.001), proximity to a
      livestock farm (0.01), proximity to farming raw materials services (0.02), and
      proximity to a nursing home (0.04) were independently associated with increased
      rates of CA-CDI. CONCLUSIONS: Our study is the first to use spatial statistics
      and mixed models to identify important environmental risk factors for acquisition
      of C. difficile and adds to the growing evidence that farm practices may put
      patients at risk for important drug-resistant infections.

PMID- 28510585
TI  - The prevalence of underweight, overweight and obesity in Bangladeshi adults: Data
      from a national survey.
AB  - BACKGROUND: Over the two last decades Bangladesh, a low-income country, has
      experienced a rapid demographic and epidemiological transition. The population
      has increased substantially with rapid urbanization and changing pattern of
      disease, which at least in part, can be explained by nutritional changes.
      However, the nutritional status of the adult population has not been previously
      described. Hence, the objective of this study was to estimate the prevalence and
      explore socio-demographic determinants of underweight, overweight and obesity
      among the Bangladeshi adult population. METHODS: This study is a secondary data
      analysis of the national 2011 Bangladesh Demographic and Health Survey. We
      determined the nutritional status of adults aged >=35 years of age, who had a
      measured weight and height, using the Asian body mass index (BMI) cut-offs for
      underweight (BMI <18.5 kg/m2), overweight (BMI 23 to <27.5 kg/m2) and obesity
      (BMI >=27.5 kg/m2). Logistic regression modeling was used to determine the
      association between socio-demographic factors and nutritional status. RESULT: Of
      total sample (n = 5495), 30.4% were underweight, 18.9% were overweight and 4.6%
      were obese. Underweight was associated with age, education and wealth. The
      adjusted odd ratios for underweight were higher for older people (>=70 years)
      compared to younger, the least educated compared to the most educated and the
      poorest compared to the wealthiest were 2.51 (95%CI: 1.95-3.23, p<0.001), 3.59
      (95%CI: 2.30-5.61, p<0.001) and 3.70 (95%CI: 2.76-4.96, p<0.001), respectively.
      Younger age (35-44 years), being female, higher education, wealthier and living
      in urban areas were associated with overweight/obesity with adjusted odds ratios
      of 1.73 (95%CI: 1.24-2.41, p<0.001), 2.48 (95%CI: 1.87-3.28, p<0.001), 3.98
      (95%CI: 2.96-5.33, p<0.001), 7.14 (95%CI: 5.20-9.81, p<0.001) 1.27 (95%CI: 1.05
      1.55, p-0.02), respectively. CONCLUSION: Underweight and overweight/obesity are
      prevalent in Bangladeshi adults. Both conditions are associated with increased
      morbidity and mortality and increase the risk of developing non-communicable
      diseases. Effective public health intervention approaches are necessary to
      address both these conditions.

PMID- 28510586
TI  - Truncation of the TAR DNA-binding protein 43 is not a prerequisite for
      cytoplasmic relocalization, and is suppressed by caspase inhibition and by
      introduction of the A90V sequence variant.
AB  - The RNA-binding and -processing protein TAR DNA-binding protein 43 (TDP-43) is
      heavily linked to the underlying causes and pathology of neurodegenerative
      diseases such as amyotrophic lateral sclerosis and frontotemporal lobar
      degeneration. In these diseases, TDP-43 is mislocalized, hyperphosphorylated,
      ubiquitinated, aggregated and cleaved. The importance of TDP-43 cleavage in the
      disease pathogenesis is still poorly understood. Here we detail the use of D
      sorbitol as an exogenous stressor that causes TDP-43 cleavage in HeLa cells,
      resulting in a 35 kDa truncated product that accumulates in the cytoplasm within
      one hour of treatment. We confirm that the formation of this 35 kDa cleavage
      product is mediated by the activation of caspases. Inhibition of caspases blocks
      the cleavage of TDP-43, but does not prevent the accumulation of full-length
      protein in the cytoplasm. Using D-sorbitol as a stressor and caspase activator,
      we also demonstrate that the A90V variant of TDP-43, which lies adjacent to the
      caspase cleavage site within the nuclear localization sequence of TDP-43, confers
      partial resistance against caspase-mediated generation of the 35 kDa cleavage
      product.

PMID- 28510587
TI  - Sibling method increases risk assessment estimates for type 1 diabetes.
AB  - We presented a risk assessment model to distinguish between type 1 diabetes (T1D)
      affected and unaffected siblings using only three single nucleotide polymorphism
      (SNP) genotypes. In addition we calculated the heritability from genome-wide
      identity-by-descent (IBD) sharing between full siblings. We analyzed 1,253 pairs
      of affected individuals and their unaffected siblings (750 pairs from a discovery
      set and 503 pairs from a validation set) from the T1D Genetics Consortium
      (T1DGC), applying a logistic regression to analyze the area under the receiver
      operator characteristic (ROC) curve (AUC). To calculate the heritability of T1D
      we used the Haseman-Elston regression analysis of the squared difference between
      the phenotypes of the pairs of siblings on the estimate of their genome-wide IBD
      proportion. The model with only 3 SNPs achieving an AUC of 0.75 in both datasets
      outperformed the model using the presence of the high-risk DR3/4 HLA genotype,
      namely AUC of 0.60. The heritability on the liability scale of T1D was
      approximately from 0.53 to 0.92, close to the results obtained from twin studies,
      ranging from 0.4 to 0.88.

PMID- 28510590
TI  - Community-based human-elephant conflict mitigation: The value of an evidence
      based approach in promoting the uptake of effective methods.
AB  - Human-elephant conflict (HEC) is a serious threat to elephants and can cause
      major economic losses. It is widely accepted that reduction of HEC will often
      require community-based methods for repelling elephants but there are few tests
      of such methods. We tested community-based crop-guarding methods with and without
      novel chili-based elephant deterrents and describe changes in farmers'
      willingness to adopt these methods following our demonstration of their relative
      effectiveness. In three separate field-trials that took place over almost two
      years (October 2005 -May 2007) in two villages adjacent to Way Kambas National
      Park (WKNP) in Indonesia, we found that community-based crop-guarding was
      effective at keeping Asian elephants (Elephas maximus) out of crop fields in
      91.2% (52 out of 57), 87.6% (156 out of 178), and 80.0% (16 out of 20) of
      attempted raids. Once the method had been shown to be effective at demonstration
      sites, farmers in 16 villages around WKNP voluntarily adopted it during the July
      2008 to March 2009 period and were able to repel elephants in 73.9% (150 out of
      203) of attempted raids, with seven villages repelling 100% of attempted raids.
      These 16 villages had all experienced high levels of HEC in the preceding years;
      e.g. they accounted for >97% of the 742 HEC incidents recorded for the entire
      park in 2006. Our work shows, therefore, that a simple evidence-based approach
      can facilitate significant reductions in HEC at the protected area scale.

PMID- 28510588
TI  - Evolutionary restoration of fertility in an interspecies hybrid yeast, by whole
      genome duplication after a failed mating-type switch.
AB  - Many interspecies hybrids have been discovered in yeasts, but most of these
      hybrids are asexual and can replicate only mitotically. Whole-genome duplication
      has been proposed as a mechanism by which interspecies hybrids can regain
      fertility, restoring their ability to perform meiosis and sporulate. Here, we
      show that this process occurred naturally during the evolution of
      Zygosaccharomyces parabailii, an interspecies hybrid that was formed by mating
      between 2 parents that differed by 7% in genome sequence and by many
      interchromosomal rearrangements. Surprisingly, Z. parabailii has a full sexual
      cycle and is genetically haploid. It goes through mating-type switching and
      autodiploidization, followed by immediate sporulation. We identified the key
      evolutionary event that enabled Z. parabailii to regain fertility, which was
      breakage of 1 of the 2 homeologous copies of the mating-type (MAT) locus in the
      hybrid, resulting in a chromosomal rearrangement and irreparable damage to 1 MAT
      locus. This rearrangement was caused by HO endonuclease, which normally functions
      in mating-type switching. With 1 copy of MAT inactivated, the interspecies hybrid
      now behaves as a haploid. Our results provide the first demonstration that MAT
      locus damage is a naturally occurring evolutionary mechanism for whole-genome
      duplication and restoration of fertility to interspecies hybrids. The events that
      occurred in Z. parabailii strongly resemble those postulated to have caused
      ancient whole-genome duplication in an ancestor of Saccharomyces cerevisiae.

PMID- 28510591
TI  - The case for investing in the male condom.
AB  - When used correctly and consistently, the male condom offers triple protection
      from unintended pregnancy and the transmission of sexually transmitted infections
      (STIs) and human immunodeficiency virus (HIV). However, with health funding
      levels stagnant or falling, it is important to understand the cost and health
      impact associated with prevention technologies. This study is one of the first to
      attempt to quantify the cost and combined health impact of condom use, as a means
      to prevent unwanted pregnancy and to prevent transmission of STIs including HIV.
      This paper describes the analysis to make the case for investment in the male
      condom, including the cost, impact and cost-effectiveness by three scenarios (low
      in which 2015 condom use levels are maintained; medium in which condom use trends
      are used to predict condom use from 2016-2030; and high in which condom use is
      scaled up, as part of a package of contraceptives, to meet all unmet need for
      family planning by 2030 and to 90% for HIV and STI prevention by 2016) for 81
      countries from 2015-2030. An annual gap between current and desired use of 10.9
      billion condoms was identified (4.6 billion for family planning and 6.3 billion
      for HIV and STIs). Under a high scenario that completely reduces that gap between
      current and desired use of 10.9 billion condoms, we found that by 2030 countries
      could avert 240 million DALYs. The additional cost in the 81 countries through
      2030 under the medium scenario is $1.9 billion, and $27.5 billion under the high
      scenario. Through 2030, the cost-effectiveness ratios are $304 per DALY averted
      for the medium and $115 per DALY averted for the high scenario. Under the three
      scenarios described above, our analysis demonstrates the cost-effectiveness of
      the male condom in preventing unintended pregnancy and HIV and STI new
      infections. Policy makers should increase budgets for condom programming to
      increase the health return on investment of scarce resources.

PMID- 28510589
TI  - Establishment of a combination scoring method for diagnosis of ocular adnexal
      lymphoproliferative disease.
AB  - Lymphoproliferative diseases (LPDs) of the ocular adnexa encompass the majority
      of orbital diseases and include reactive follicular hyperplasia (RFH), atypical
      lymphoid hyperplasia (ALH), and mucosa-associated lymphoid tissue lymphoma
      (MALToma). Lymphoid follicles (LFs) are usually observed during the histological
      examination of LPDs. Currently, because there is a lack of specific clinical
      signs and diagnostic immunohistochemical biomarkers, it is difficult for
      pathologists to distinguish MALToma from ocular RFH and ALH, which makes the
      clinical management of these conditions difficult. Here, we analyzed the clinical
      features of patients with ocular adnexal LPDs (n = 125) and investigated the
      structure of LFs in paraffin-embedded tissue samples using anti-CD23 and anti-IgD
      immunochemistry. We found that some clinical features including age, sex, and
      laterality were different among RFH, LFH, and MALToma. Additionally,
      immunohistochemistry revealed that the expression of IgD and CD23 was higher in
      RFH patients and decreased in patients with ALH and MALToma. Moreover, LFs in RFH
      were intact, whereas the structures of most LFs were disrupted in ALH. In MALToma
      specimens, few intact LFs were observed. In a further investigation, we combined
      the results for CD23/IgD immunohistochemistry and the structure of LFs to
      establish a scoring method for the differential diagnosis of LPDs. According to
      the BIOMED-2 protocol, we further detected IgH gene monoclonal rearrangement in
      73 cases (35 RFH, 17 ALH, and 21 MALToma cases). The sensitivity of our scoring
      method, based on a comparison with the results of IgH gene monoclonal
      rearrangement detection, was 85.7% (18/21) for MALToma and 35.3% (6/17) for ALH.
      Our study provides a method that may be useful for the differential diagnosis of
      RFH, ALH, and MALToma.

PMID- 28510592
TI  - Alteration of protein function by a silent polymorphism linked to tRNA abundance.
AB  - Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for
      protein function, as by definition they exchange only codons, not amino acids. We
      identified an sSNP that modifies the local translation speed of the cystic
      fibrosis transmembrane conductance regulator (CFTR), leading to detrimental
      changes to protein stability and function. This sSNP introduces a codon pairing
      to a low-abundance tRNA that is particularly rare in human bronchial epithelia,
      but not in other human tissues, suggesting tissue-specific effects of this sSNP.
      Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of
      the sSNP and rescues protein conformation and function. Our results highlight the
      wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA
      translation and provide direct evidence for the central role of cellular tRNA
      levels in mediating the actions of sSNPs in a tissue-specific manner.

PMID- 28510593
TI  - No serological evidence for Zika virus infection and low specificity for anti
      Zika virus ELISA in malaria positive individuals among pregnant women from
      Madagascar in 2010.
AB  - It was previously reported that a malaria infection may interfere with the
      specificity of a commercial ELISA test against Zika virus (ZIKV). We analyzed
      1,216 plasma samples from healthy, pregnant women collected in two sites in
      Madagascar in 2010 for ZIKV antibodies using a commercial ELISA and for
      Plasmodium infection by PCR. This screen revealed six putative ZIKV-positive
      samples by ELISA. These results could not be confirmed by indirect
      immunofluorescence assays or virus neutralization tests. Four of these six
      samples were also positive for P. falciparum. We noted that the frequency of
      malaria positivity was higher in ZIKV-ELISA positive samples (50% and 100% in the
      two study sites) than ZIKV-negative samples (17% and 10%, respectively),
      suggesting that malaria may have led to false ZIKV-ELISA positives.

PMID- 28510596
TI  - Utilization of growth monitoring and promotion services and associated factors
      among under two years of age children in Southern Ethiopia.
AB  - Growth monitoring and promotion (GMP) is a prevention activity comprised of
      growth monitoring (GM) linked with promotion that serves as the core activity in
      an integrated child health and nutrition program. However, different methods of
      institutional studies have shown that utilization of GM services has remained to
      be inadequate. There is scarcity of studies conducted about GMP in quantitative
      method. Therefore, this study was conducted to address the proportion of GMP
      services and associated factors among children under two years of age in rural
      communities of Mareka district, Southern Ethiopia. Community based cross
      sectional survey was conducted from August to September 2015. Single population
      proportion formula was used to determine the sample size with multi stage
      sampling technique. A total of 819 children under two years of age were included.
      Pretest was done on 10% of the total sample size. Data were analyzed using SPSS
      version 20.0 software. Bivariate and multivariate logistic regressions used to
      analyze data. The response rate was 95%. Utilization of GMP services was 16.9%.
      Institutional delivery AOR (95% CI): 3.01(1.65-5.50), index child age 12-17
      months AOR (95% CI): 4.03(2.16-7.51) and 18-23 months AOR (95% CI): 3.08(1.70
      5.57), family size 4-5 AOR(95% CI): 0.14(0.06-0.33), family size >5 AOR(95% CI):
      0.34(0.14-0.82), regular GMP attendance AOR (95% CI): 4.37(2.45-7.80), medium
      wealth index AOR(95% CI): 3.14(1.51-6.52) and high wealth index AOR(95% CI):
      3.24(1.59-6.62) were factors associated with utilization of GMP services.
      Utilization of GMP services was low. Thus, efforts should be made to improve
      utilization of GMP services through promotion of institutional delivery,
      different family planning methods, and regular GMP attendance.

PMID- 28510594
TI  - Long term type 1 diabetes is associated with hand pain, disability and stiffness
      but not with structural hand osteoarthritis features - The Dialong hand study.
AB  - OBJECTIVE: To explore whether having long-term type 1 diabetes (>45 years) is
      associated with a higher prevalence of radiographic hand OA, erosive hand OA and
      increased hand pain, disability and stiffness. METHODS: In total N = 96 persons
      with type 1 diabetes diagnosed before 1970 were included (mean [SD] age: 62.2
      [7.4], mean [SD] HbA1c: 7.43 [0.80] and N = 49 [51%] men). Regular measurements
      of their HbA1c were obtained till 2015. We included N = 69 healthy controls
      without any diabetes (mean [SD] age: 63.0 [7.0], mean [SD] HbA1c: 5.41 [0.32], N
      = 29 [42%] men). The groups were compared for radiographic hand OA (Kellgren
      Lawrence grade >=2 in >=1 joint) and erosive hand OA (central erosions in >=1
      joint), Australian/Canadian index (AUSCAN) for hand pain, disability and
      stiffness using regression analyses adjusted for age, sex, educational level and
      waist circumference. RESULTS: We found no associations between having long term
      type 1 diabetes and more prevalent radiographic hand OA (OR = 0.83, 95% CI = 0.38
      1.81). We found a trend towards higher prevalence of erosive hand OA in diabetes
      patients (OR = 2.96, 95% CI = 0.82-10.64). Strong and consistent associations
      were observed between long term type 1 diabetes and increased hand pain (B =
      2.78, 95% CI = 1.65-3.91), disability (B = 5.30, 95% CI = 3.48-7.12) and
      stiffness (B = 2.00, 95% CI = 1.33-2.67). These associations were particularly
      strong for women and participants below the median age of 61 years. CONCLUSION:
      Long-term type 1 diabetes was not associated with radiographic hand OA, but was
      strongly associated with hand pain, disability and stiffness. The association
      between diabetes and erosive hand OA warrants further investigation.

PMID- 28510595
TI  - Structural adaptations of octaheme nitrite reductases from haloalkaliphilic
      Thioalkalivibrio bacteria to alkaline pH and high salinity.
AB  - Bacteria Tv. nitratireducens and Tv. paradoxus from soda lakes grow optimally in
      sodium carbonate/NaCl brines at pH range from 9.5 to 10 and salinity from 0.5 to
      1.5 M Na+. Octaheme nitrite reductases (ONRs) from haloalkaliphilic bacteria of
      genus Thioalkalivibrio are stable and active in a wide range of pH (up to 11) and
      salinity (up to 1 M NaCl). To establish adaptation mechanisms of ONRs from
      haloalkaliphilic bacteria a comparative analysis of amino acid sequences and
      structures of ONRs from haloalkaliphilic bacteria and their homologues from non
      halophilic neutrophilic bacteria was performed. The following adaptation
      strategies were observed: (1) strategies specific for halophilic and alkaliphilic
      proteins (an increase in the number of aspartate and glutamate residues and a
      decrease in the number of lysine residues on the protein surface), (2) strategies
      specific for halophilic proteins (an increase in the arginine content and a
      decrease in the number of hydrophobic residues on the solvent-accessible protein
      surface), (3) strategies specific for alkaliphilic proteins (an increase in the
      area of intersubunit hydrophobic contacts). Unique adaptation mechanism inherent
      in the ONRs from bacteria of genus Thioalkalivibrio was revealed (an increase in
      the core in the number of tryptophan and phenylalanine residues, and an increase
      in the number of small side chain residues, such as alanine and valine, in the
      core).

PMID- 28510597
TI  - Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.
AB  - The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two
      multi-component complexes involved in transcription regulation. In the context of
      complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription
      initiation of many nuclear housekeeping genes and of mitochondrial genes. While
      this function is conserved in metazoans, MOF has an additional, specific function
      in Drosophila in the context of dosage compensation. As a subunit of the male
      specific-lethal dosage compensation complex (MSL-DCC) it contributes to the
      doubling of transcription output from the single male X chromosome by acetylating
      histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC
      and an appropriate distribution of MOF between the regulatory complexes. The
      amounts of DCC formed depends directly on the levels of the male-specific MSL2,
      which orchestrates the assembly of the DCC, including MOF recruitment. We found
      earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including
      MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's
      overall levels and folding state as well as its partitioning between the complex
      entities. We now used mass spectrometry to map the lysines in MOF that are
      ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF
      in male and female cells. MSL2-specific ubiquitylation in vivo could not be
      traced due to the dominance of other, sex-independent ubiquitylation events and
      conceivably may be rare or transient. Expressing appropriately mutated MOF
      derivatives we assessed the importance of the ubiquitylated lysines for dosage
      compensation by monitoring DCC formation and X chromosome targeting in cultured
      cells, and by genetic complementation of the male-specific-lethal mof2 allele in
      flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a
      reference for future studies.

PMID- 28510598
TI  - Age, gender, neck circumference, and Epworth sleepiness scale do not predict
      obstructive sleep apnea (OSA) in moderate to severe chronic obstructive pulmonary
      disease (COPD): The challenge to predict OSA in advanced COPD.
AB  - The combination of chronic obstructive pulmonary disease (COPD) and obstructive
      sleep apnea (OSA) is associated with substantial morbidity and mortality. We
      hypothesized that predictors of OSA among patients with COPD may be distinct from
      OSA in the general population. Therefore, we investigated associations between
      traditional OSA risk factors (e.g. age), and sleep questionnaires [e.g. Epworth
      Sleepiness Scale] in 44 patients with advanced COPD. As a second aim we proposed
      a pilot, simplified screening test for OSA in patients with COPD. In a
      prospective, observational study of patients enrolled in the UCSD Pulmonary
      Rehabilitation Program we collected baseline characteristics, cardiovascular
      events (e.g. atrial fibrillation), and sleep questionnaires [e.g. Pittsburgh
      Sleep Quality Index (PSQI)]. For the pilot questionnaire, a BMI >=25 kg/m2 and
      the presence of cardiovascular disease were used to construct the pilot screening
      test. Male: 59%; OSA 66%. FEV1 (mean +/- SD) = 41.0+/-18.2% pred., FEV1/FVC =
      41.5+/-12.7%]. Male gender, older age, and large neck circumference were not
      associated with OSA. Also, Epworth Sleepiness Scale and the STOP-Bang
      questionnaire were not associated with OSA in univariate logistic regression. In
      contrast, BMI >=25 kg/m2 (OR = 3.94, p = 0.04) and diagnosis of cardiovascular
      disease (OR = 5.06, p = 0.03) were significantly associated with OSA [area under
      curve (AUC) = 0.74]. The pilot COPD-OSA test (OR = 5.28, p = 0.05) and STOP-Bang
      questionnaire (OR = 5.13, p = 0.03) were both associated with OSA in Receiver
      Operating Characteristics (ROC) analysis. The COPD-OSA test had the best AUC
      (0.74), sensitivity (92%), and specificity (83%). A ten-fold cross-validation
      validated our results. We found that traditional OSA predictors (e.g. gender,
      Epworth score) did not perform well in patients with more advanced COPD. Our
      pilot test may be an easy to implement instrument to screen for OSA. However, a
      larger validation study is necessary before further clinical implementation is
      warranted.

PMID- 28510599
TI  - Selective inhibition of brain endothelial Rho-kinase-2 provides optimal
      protection of an in vitro blood-brain barrier from tissue-type plasminogen
      activator and plasmin.
AB  - Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may
      protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced
      damage. While the use of nonselective ROCK inhibitors like fasudil together with
      rt-PA may be hindered by possible hypotensive side-effects and inadequate
      capacity to block detrimental rt-PA activity in brain endothelial cells (BECs),
      selective ROCK-2 inhibition may overcome these limitations. Here, we examined
      ROCK-2 expression in major brain cells and compared the ability of fasudil and
      KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in
      an in vitro human model. ROCK-2 was highly expressed relative to ROCK-1 in all
      human and mouse brain cell types and particularly enriched in rodent brain
      endothelial cells and astrocytes compared to neurons. KD025 was more potent than
      fasudil in attenuation of rt-PA- and plasminogen-induced BBB permeation under
      normoxia, but especially under stroke-like conditions. Importantly, only KD025,
      but not fasudil, was able to block rt-PA-dependent permeability increases,
      morphology changes and tight junction degradation in isolated BECs. Selective
      ROCK-2 inhibition further diminished rt-PA-triggered myosin phosphorylation,
      shape alterations and matrix metalloprotease activation in astrocytes. These
      findings highlight ROCK-2 as the key isoform driving BBB impairment and brain
      endothelial damage by rt-PA and the potential of KD025 to optimally protect the
      BBB during thrombolysis.

PMID- 28510601
TI  - Reproductive biology of the deep brooding coral Seriatopora hystrix: Implications
      for shallow reef recovery.
AB  - Mesophotic coral ecosystems (MCEs, between 30 and 150 m depth) are hypothesized
      to contribute to the recovery of degraded shallow reefs through sexually produced
      larvae (referred to as Deep Reef Refuge Hypothesis). In Okinawa, Japan, the
      brooder coral Seriatopora hystrix was reported to be locally extinct in a shallow
      reef while it was found abundant at a MCE nearby. In this context, S. hystrix
      represents a key model to test the Deep Reef Refuge Hypothesis and to understand
      the potential contribution of mesophotic corals to shallow coral reef recovery.
      However, the reproductive biology of mesophotic S. hystrix and its potential to
      recolonize shallow reefs is currently unknown. This study reports for the first
      time, different temporal scales of reproductive periodicity and larval settlement
      of S. hystrix from an upper mesophotic reef (40 m depth) in Okinawa. We examined
      reproductive seasonality, lunar, and circadian periodicity (based on polyp
      dissection, histology, and ex situ planula release observations) and larval
      settlement rates in the laboratory. Mesophotic S. hystrix reproduced mainly in
      July and early August, with a small number of planulae being released at the end
      of May, June and August. Compared to shallow colonies in the same region,
      mesophotic S. hystrix has a 4-month shorter reproductive season, similar
      circadian periodicity, and smaller planula size. In addition, most of the
      planulae settled rapidly, limiting larval dispersal potential. The shorter
      reproductive season and smaller planula size may result from limited energy
      available for reproduction at deeper depths, while the similar circadian
      periodicity suggests that this reproductive aspect is not affected by
      environmental conditions differing with depth. Overall, contribution of
      mesophotic S. hystrix to shallow reef rapid recovery appears limited, although
      they may recruit to shallow reefs through a multistep process over a few
      generations or through random extreme mixing such as typhoons.

PMID- 28510600
TI  - Complete Comparison Display (CCD) evaluation of ethanol extracts of Centella
      asiatica and Withania somnifera shows that they can non-synergistically
      ameliorate biochemical and behavioural damages in MPTP induced Parkinson's model
      of mice.
AB  - Parkinson's disease remains as one of the most common debilitating
      neurodegenerative disorders. With the hopes of finding agents that can cure or
      reduce the pace of progression of the disease, we studied two traditional
      medicinal plants: Centella asiatica and Withania somnifera that have been
      explored in some recent studies. In agreement with the previous work on ethanol
      extracts of these two plants in mice model, we saw an improvement in oxidative
      stress profile as well as behavioral performance in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) induced Parkinson-like symptoms in Balb/c mice. Given
      the known potential of both the herbal extracts in improving Parkinson-like
      symptoms, we expected the combination of the two to show better results than
      either of the two but surprisingly there was no additivity in either oxidative
      stress or behavioural recovery. In fact, in some assays, the combination
      performed worse than either of the two individual constituents. This effect of
      mixtures highlights the need of testing mixtures in supplements market using
      enthomedicine. The necessity of comparing multiple groups in this study to get
      most information from the experiments motivated us to design a ladder-like
      visualization to show comparison with different groups that we call complete
      comparison display (CCD). In summary, we show the potential of Centella asiatica
      and Withania somnifera to ameliorate Parkinson's disorder.

PMID- 28510602
TI  - Tree-based approach for exploring marine spatial patterns with raster datasets.
AB  - From multiple raster datasets to spatial association patterns, the data-mining
      technique is divided into three subtasks, i.e., raster dataset pretreatment,
      mining algorithm design, and spatial pattern exploration from the mining results.
      Comparison with the former two subtasks reveals that the latter remains
      unresolved. Confronted with the interrelated marine environmental parameters, we
      propose a Tree-based Approach for eXploring Marine Spatial Patterns with multiple
      raster datasets called TAXMarSP, which includes two models. One is the Tree-based
      Cascading Organization Model (TCOM), and the other is the Spatial Neighborhood
      based CAlculation Model (SNCAM). TCOM designs the "Spatial node->Pattern node"
      from top to bottom layers to store the table-formatted frequent patterns.
      Together with TCOM, SNCAM considers the spatial neighborhood contributions to
      calculate the pattern-matching degree between the specified marine parameters and
      the table-formatted frequent patterns and then explores the marine spatial
      patterns. Using the prevalent quantification Apriori algorithm and a real remote
      sensing dataset from January 1998 to December 2014, a successful application of
      TAXMarSP to marine spatial patterns in the Pacific Ocean is described, and the
      obtained marine spatial patterns present not only the well-known but also new
      patterns to Earth scientists.

PMID- 28510603
TI  - Effectiveness of community-based peer support for mothers to improve their
      breastfeeding practices: A systematic review and meta-analysis.
AB  - METHODS: We searched for evidence regarding community-based peer support for
      mothers in databases, such as PubMed/MEDLINE, the Cochrane Library, CINAHL, Web
      of Science, SocINDEX, and PsycINFO. We selected three outcome variables for
      breastfeeding practices, namely, exclusive breastfeeding duration, breastfeeding
      within the first hour of life, and prelacteal feeding. We conducted meta-analyses
      of the included randomized controlled trials and quasi-experimental studies.
      RESULTS: For our review, we selected 47 articles for synthesis out of 1,855
      retrieved articles. In low- and middle-income countries, compared to usual care,
      community-based peer support increased exclusive breastfeeding at 3 months (RR:
      1.90, 95% CI: 1.62-2.22), at 5 months (RR: 9.55, 95% CI: 6.65-13.70) and at 6
      months (RR: 3.53, 95% CI: 2.49-5.00). In high-income countries, compared to usual
      care, peer support increased exclusive breastfeeding at 3 months (RR: 2.61, 95%
      CI: 1.15-5.95). In low- and middle-income countries, compared to usual care, peer
      support increased the initiation of breastfeeding within the first hour of life
      (RR: 1.51, 95% CI: 1.04-2.21) and decreased the risk of prelacteal feeding (RR:
      0.38, 95% CI: 0.33-0.45). CONCLUSIONS: Community-based peer support for mothers
      is effective in increasing the duration of exclusive breastfeeding, particularly
      for infants aged 3-6 months in low- and middle-income countries. Such support
      also encourages mothers to initiate breastfeeding early and prevents newborn
      prelacteal feeding.

PMID- 28510604
TI  - Ebola exposure, illness experience, and Ebola antibody prevalence in
      international responders to the West African Ebola epidemic 2014-2016: A cross
      sectional study.
AB  - BACKGROUND: Healthcare and other front-line workers are at particular risk of
      infection with Ebola virus (EBOV). Despite the large-scale deployment of
      international responders, few cases of Ebola virus disease have been diagnosed in
      this group. Since asymptomatic or pauci-symptomatic infection has been described,
      it is plausible that infections have occurred in healthcare workers but have
      escaped being diagnosed. We aimed to assess the prevalence of asymptomatic or
      pauci-symptomatic infection, and of exposure events, among returned responders to
      the West African Ebola epidemic 2014-2016. METHODS AND FINDINGS: We used snowball
      sampling to identify responders who had returned to the UK or Ireland, and used
      an online consent and questionnaire to determine their exposure to EBOV and their
      experience of illness. Oral fluid collection devices were sent and returned by
      post, and samples were tested using an EBOV IgG capture assay that detects IgG to
      Ebola glycoprotein. Blood was collected from returnees with reactive samples for
      further testing. Unexposed UK controls were also recruited. In all, 300
      individuals consented, of whom 268 (89.3%) returned an oral fluid sample (OFS).
      The majority had worked in Sierra Leone in clinical, laboratory, research, and
      other roles. Fifty-three UK controls consented and provided samples using the
      same method. Of the returnees, 47 (17.5%) reported that they had had a possible
      EBOV exposure. Based on their free-text descriptions, using a published risk
      assessment method, we classified 43 (16%) as having had incidents with risk of
      Ebola transmission, including five intermediate-risk and one high-risk exposure.
      Of the returnees, 57 (21%) reported a febrile or diarrhoeal illness in West
      Africa or within 1 mo of return, of whom 40 (70%) were not tested at the time for
      EBOV infection. Of the 268 OFSs, 266 were unreactive. Two returnees, who did not
      experience an illness in West Africa or on return, had OFSs that were reactive on
      the EBOV IgG capture assay, with similar results on plasma. One individual had no
      further positive test results; the other had a positive result on a double
      antigen bridging assay but not on a competitive assay or on an indirect EBOV IgG
      ELISA. All 53 controls had non-reactive OFSs. While the participants were not a
      random sample of returnees, the number participating was high. CONCLUSIONS: This
      is the first study, to our knowledge, of the prevalence of EBOV infection in
      international responders. More than 99% had clear negative results. Sera from two
      individuals had discordant results on the different assays; both were negative on
      the competitive assay, suggesting that prior infection was unlikely. The finding
      that a significant proportion experienced "near miss" exposure events, and that
      most of those who experienced symptoms did not get tested for EBOV at the time,
      suggests a need to review and standardise protocols for the management of
      possible exposure to EBOV, and for the management of illness, across
      organisations that deploy staff to outbreaks.

PMID- 28510605
TI  - The role of attention in human motor resonance.
AB  - Observation of others' actions evokes in primary motor cortex and spinal circuits
      of observers a subliminal motor resonance response, which reflects the motor
      program encoding observed actions. We investigated the role of attention in human
      motor resonance with four experimental conditions, explored in different subject
      groups: in the first explicit condition, subjects were asked to observe a
      rhythmic hand flexion-extension movement performed live in front of them. In two
      other conditions subjects had to monitor the activity of a LED light mounted on
      the oscillating hand. The hand was clearly visible but it was not the focus of
      subjects' attention: in the semi-implicit condition hand movement was relevant to
      task completion, while in the implicit condition it was irrelevant. In a fourth,
      baseline, condition subjects observed the rhythmic oscillation of a metal
      platform. Motor resonance was measured with the H-reflex technique as the
      excitability modulation of cortico-spinal motorneurons driving a hand flexor
      muscle. As expected, a normal resonant response developed in the explicit
      condition, and no resonant response in the baseline condition. Resonant responses
      also developed in both semi-implicit and implicit conditions and, surprisingly,
      were not different from each other, indicating that viewing an action is, per se,
      a powerful stimulus for the action observation network, even when it is not the
      primary focus of subjects' attention and even when irrelevant to the task.
      However, the amplitude of these responses was much reduced compared to the
      explicit condition, and the phase-lock between the time courses of observed
      movement and resonant motor program was lost. In conclusion, different parameters
      of the response were differently affected by subtraction of attentional resources
      with respect to the explicit condition: time course and muscle selection were
      preserved while the activation of motor circuits resulted in much reduced
      amplitude and lost its kinematic specificity.

PMID- 28510606
TI  - Safety and efficacy of cell-free and concentrated ascites reinfusion therapy
      (CART) in refractory ascites: Post-marketing surveillance results.
AB  - We performed post-marketing surveillance to evaluate the safety and efficacy of
      cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART
      sessions in 147 patients at 22 centers were performed. The most common primary
      disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected
      was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein
      was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine
      volume, body weight and abdominal circumference were significantly improved after
      CART. Body temperature increased significantly, by 0.3 degrees C on average.
      Concomitant steroids and/or NSAIDs use before reinfusion was significantly and
      negatively associated with increases in body temperature. Most adverse events
      were fever and chills. This study examined a large number of patients compared
      with previous studies, and showed that CART is an effective and relatively safe
      treatment for refractory ascites, such as malignant ascites.

PMID- 28510607
TI  - Recent evolutionary history of Chrysoperla externa (Hagen 1861) (Neuroptera:
      Chrysopidae) in Brazil.
AB  - This work aimed to elucidate the distribution of Chrysoperla externa haplotypes
      and investigate whether it exhibits structure based on genetic composition as
      opposed to geographic location. The genetic diversity of C. externa, analyzed by
      AMOVA using the COI and 16S rRNA genes as mitochondrial markers, showed
      significant haplotype structure arising from genetic differences that was not
      associated with sampling location. This was reflected in the network grouping.
      Bayesian inference showed that haplotype distribution may have its origins in C.
      externa divergence into two distinct clades, which dispersed to various
      locations, and their subsequent diversification. The evolutionary history of C.
      externa may include multiple ancestral haplotypes differentiating within the same
      geographic area to generate the current broad genetic diversity, so that the
      earlier geographical history has been erased, and now we have highlighted its
      more recent genetic history.

PMID- 28510609
TI  - SPR-based fragment screening with neurotensin receptor 1 generates novel small
      molecule ligands.
AB  - The neurotensin receptor 1 represents an important drug target involved in
      various diseases of the central nervous system. So far, the full exploitation of
      potential therapeutic activities has been compromised by the lack of compounds
      with favorable physicochemical and pharmacokinetic properties which efficiently
      penetrate the blood-brain barrier. Recent progress in the generation of
      stabilized variants of solubilized neurotensin receptor 1 and its subsequent
      purification and successful structure determination presents a solid starting
      point to apply the approach of fragment-based screening to extend the chemical
      space of known neurotensin receptor 1 ligands. In this report, surface plasmon
      resonance was used as primary method to screen 6369 compounds. Thereby 44 hits
      were identified and confirmed in competition as well as dose-response
      experiments. Furthermore, 4 out of 8 selected hits were validated using nuclear
      magnetic resonance spectroscopy as orthogonal biophysical method. Computational
      analysis of the compound structures, taking the known crystal structure of the
      endogenous peptide agonist into consideration, gave insight into the potential
      fragment-binding location and interactions and inspires chemistry efforts for
      further exploration of the fragments.

PMID- 28510608
TI  - The Biomphalaria glabrata DNA methylation machinery displays spatial tissue
      expression, is differentially active in distinct snail populations and is
      modulated by interactions with Schistosoma mansoni.
AB  - BACKGROUND: The debilitating human disease schistosomiasis is caused by infection
      with schistosome parasites that maintain a complex lifecycle alternating between
      definitive (human) and intermediate (snail) hosts. While much is known about how
      the definitive host responds to schistosome infection, there is comparably less
      information available describing the snail's response to infection.
      METHODOLOGY/PRINCIPLE FINDINGS: Here, using information recently revealed by
      sequencing of the Biomphalaria glabrata intermediate host genome, we provide
      evidence that the predicted core snail DNA methylation machinery components are
      associated with both intra-species reproduction processes and inter-species
      interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA
      methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal
      compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly
      inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA
      methyltransferase activity and 5mC binding in pigmented hybrid- compared to
      inbred (NMRI)- B. glabrata populations indicate a role for the snail's DNA
      methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus
      specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic
      region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in
      silico predictions and whole genome BS-Seq analysis of this species' genome.
      Finally, we provide preliminary evidence for parasite-mediated host epigenetic
      reprogramming in the schistosome/snail system, as demonstrated by the increase in
      Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic
      cell line) exposure to parasite larval transformation products (LTP).
      CONCLUSIONS/SIGNIFICANCE: The presence of a functional DNA methylation machinery
      in B. glabrata as well as the modulation of these gene products in response to
      schistosome products, suggests a vital role for DNA methylation during snail
      development/oviposition and parasite interactions. Further deciphering the role
      of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary
      biology may reveal key factors associated with disease transmission and,
      moreover, enable the discovery of novel lifecycle intervention strategies.

PMID- 28510611
TI  - MMP-10, MMP-7, TIMP-1 and TIMP-2 mRNA expression in esophageal cancer.
AB  - INTRODUCTION: Tissue inhibitors of metalloproteinases (TIMP) and the matrix
      metalloproteinases (MMP) are involved in the spread of cancer. METHODS: We have
      evaluated the matrix metalloproteinases' (MMP-10, MMP-7) and their inhibitors'
      (tissue inhibitors of metalloproteinases - TIMP-1, TIMP-2) mRNA expression in 61
      esophageal cancer samples from patients who had undergone surgery, by using real
      time quantitative RT-PCR, and correlated the results with the patient
      clinicopathologic features. RESULTS: MMP-10, MMP-7, TIMP-1, TIMP-2 were
      overexpressed in 73%, 85%, 55% and 42% of esophageal cancer samples,
      respectively. The expression of MMP-10, TIMP-1, and TIMP-2 correlated with the
      tumor size. The MMP-7 overexpression was associated with the tumour stage (I, II
      vs III, p=0.05) and lymph node metastasis (N0 vs N1, p=0.037). CONCLUSIONS: We
      conclude that in the resected esophageal cancer an increased mRNA expression of
      MMP-7, MMP-10 and TIMP-1 correlated with clinicopathologic features. We suggest
      that these genes may play a role during progression of the disease.

PMID- 28510610
TI  - Insulin resistance contributes more to the increased risk for diabetes
      development in subjects with low lipoprotein(a) level than insulin secretion.
AB  - BACKGROUND: Recent studies suggest an association between Lipoprotein(a) [Lp(a)]
      and the development of diabetes mellitus. We analyzed the association between
      baseline Lp(a) levels and diabetes development after 4 years of follow-up, in a
      population of apparently healthy Korean subjects. METHODS: A total of 2,536 non
      diabetic participants (mean age: 41 years, men: 92%) of a health checkup program
      were included in the study. Diabetes development was defined by fasting blood
      glucose >=126 mg/dL, HbA1c >=6.5%, and self-reported treatment of diabetes.
      Homeostasis model assessment (HOMA) indices were used to assess insulin
      resistance (IR) and insulin secretion (IS). Presence of IR and impaired IS was
      defined by being in the highest quartile of HOMA-IR and in the lowest quartile
      HOMA-IS. RESULTS: After four years, 3.4% of the participants developed diabetes.
      The odds ratio (OR) of developing diabetes was lowest in the 4th quartile group
      of baseline Lp(a) (0.323 [95% CI 0.153-0.685])with the 1st quartile group as the
      reference. The subjects with both IR & impaired IS plus baseline Lp(a)<50 mg/dL
      showed the higher OR for diabetes development compared with those without IR and
      normal IS as the reference (67.277 [20.218-223.871], and those with IR plus
      Lp(a)<50 mg/dL showed higher OR for diabetes than in those with impaired IS and
      Lp(a)<50 mg/dL (3.811 [1.938-7.495] vs. 3.452 [1.620-7.353]). CONCLUSIONS: The
      subjects with low baseline Lp(a) level showed higher risk for development of
      diabetes compared with high baseline Lp(a) level, and this was prominent in those
      with IR than in those with impaired IS.

PMID- 28510613
TI  - Preliminary report on beta-casein gene Met183QVal183 polymorphism in Romanian
      indigenous Zackel sheep breeds.
AB  - Genetic polymorphisms of the milk protein genes are important because of their
      effects on quantitative traits and technological properties of milk
      manufacturing. In the present study we identified the polymorphism of the beta
      casein gene in two local sheep breeds (Racka n=98 and Turcana n=111) in Romania.
      The most studied variants at the ovine beta-casein (CSN2) locus are: A and G
      variants. Genomic DNA was extracted from hair follicles and beta-casein genotypes
      were determined by the rapid TaqMan (Applied Biosystems, USA) genotyping assay.
      Homozygote genotypes GG were not detected in any of the studied breeds. In both,
      the Racka and Turcana breeds, the A variant had a much higher frequency, 0.98%
      and 0.97%, respectively. In the current study, the fast DNA tests for genotyping
      ovine CSN2 were successfully optimized, however, further samples and correlations
      of genomic results with milk characteristics and production data are needed for
      the development of future selection schemes of the Romanian indigenous sheep
      breeds, with the ultimate purpose to produce low allergen level sheep milk and
      derived dairy products.

PMID- 28510612
TI  - Suppression of ID1 expression in colon cancer cells increases sensitivity to 5
      fluorouracil.
AB  - Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for
      patients with advanced colorectal carcinoma. The major obstacle in successful
      treatment is the ability of CRC cells to acquire chemoresistance. Here we
      examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To
      suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with
      a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1
      showed altered expression of epithelial and mesenchymal markers and exhibited
      increased proliferation rate compared to the parental cells. HCT-116 cells with
      suppressed ID1 became sensitized to 5-FU and this was not observed in HT-29
      cells. Silencing ID1 resulted in altered expression of genes encoding enzymes
      metabolizing 5-FU. HT-29 cells with suppressed ID1 had significantly reduced mRNA
      level for thymidine phosphorylase, uridine-cytydine kinase 2 and
      dihydropyrimidine dehydrogenase. ID1 suppression in HCT-116 cells resulted in an
      increase of mRNA level for thymidine phosphorylase, thymidine kinase and uridine
      cytydine kinase 2 with concurrent drop of dihydropyrimidine dehydrogenase and
      thymidylate synthetase mRNA levels. In conclusion, ID1 expression impacts the
      sensitivity of colon cancer cells to 5-FU and may be considered as a potential
      predictive marker in CRC treatment.

PMID- 28510614
TI  - Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor
      development.
AB  - : Cellular stress responses determine tissue development, homeostasis and
      pathogenesis. Paracrine signaling, exchange of mechanical stimuli and
      intercellular transfer of small metabolites via connexin-built gap junctional
      channels are involved in the cellular stress detection and propagation of stress
      stimuli in multicellular networks. Cellular stress responses are also regulated
      through the activity of unpaired connexons (hemichannels) and via the
      intracellular interference of connexins with the cell cycle and pro-apoptotic
      machinery. Therefore, connexins are considered as multidirectional transmitters
      of the "outside-in" and "inside-out" stress signaling that are crucial for tissue
      homeostasis, regeneration and pathology. In particular, the disturbance of
      connexin function during the multi-stage process of tumor development leads to
      abnormal reactions of tumor cells to stress stimuli. In this review, we outline
      the current knowledge on the multidirectional role of connexins in the detection
      of stress signals. We also discuss the role of connexin-mediated intercellular
      transmittance of stress signals in tumour promotion, progression and metastatic
      cascade. HIGHLIGHTS: 1. Connexins and gap junctions protect cells from the
      microenvironmental stress and are involved in propagation and intracellular
      processing of stress signals. 2. The quality and quantity of stress stimuli,
      which may lead to cell adaptation or death by apoptosis, is determined by
      intrinsic properties of connexins and the cell phenotype. 3. Connexin deficiency
      increases the resistance of tumor cells to the "outside-in" stress signaling. 4.
      The connexin-mediated "inside-out" stress signaling participates in tumor cell
      invasion during the metastatic cascade.

PMID- 28510615
TI  - The Role of Frequency in Learning Morphophonological Alternations: Implications
      for Children With Specific Language Impairment.
AB  - Purpose: The aim of this article was to explore how the type of allomorph (e.g.,
      past tense buzz[d] vs. nod[ed]) influences the ability to perceive and produce
      grammatical morphemes in children with typical development and with specific
      language impairment (SLI). Method: The participants were monolingual Australian
      English-speaking children. The SLI group included 13 participants (mean age = 5;7
      [years;months]); the control group included 19 children with typical development
      (mean age = 5;4). Both groups performed a grammaticality judgment and elicited
      production task with the same set of nonce verbs in third-person singular and
      past tense forms. Results: Five-year-old children are still learning to
      generalize morphophonological patterns to novel verbs, and syllabic /ez/ and /ed/
      allomorphs are significantly more challenging to produce, particularly for the
      SLI group. The greater phonetic content of these syllabic forms did not enhance
      perception. Conclusions: Acquisition of morphophonological patterns involving low
      frequency allomorphs is still underway in 5-year-old children with typical
      development, and it is even more protracted in SLI populations, despite these
      patterns being highly predictable. Children with SLI will therefore benefit from
      targeted intervention with low-frequency allomorphs.

PMID- 28510616
TI  - Salvage high-dose chemotherapy in female patients with relapsed/refractory germ
      cell tumors: a retrospective analysis of the European Group for Blood and Marrow
      Transplantation (EBMT).
AB  - Background: High-dose chemotherapy (HDC) with hematopoietic progenitor cell
      transplantation is a standard option for relapsed/refractory testicular germ-cell
      tumor (GCT), but only few data have been reported in female patients with GCT. We
      conducted a retrospective analysis of female patients with GCT treated with HDC
      and registered with the European Society for Blood and Marrow Transplantation.
      Patients and methods: Between 1985 and 2013, 60 registered female patients with
      GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty
      patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%)
      retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%)
      received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as
      fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late
      intensification with no evidence of metastasis before HDC. The conditioning HDC
      regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single
      HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). Results: Nine
      cases who underwent late intensification HDC were not evaluable for response. Of
      the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8
      (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive
      partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease.
      There were 3 toxic deaths (6%). With an overall median follow-up of 14 months
      (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25
      patients (72%) achieving a CR/PRm- following HDC were free of
      relapse/progression. In total, 25 of 60 patients (42%) were progression-free
      following HDC at a median follow-up of 87 months (range 3-219 months).
      Conclusions: Salvage HDC based on carboplatin represents a therapeutic option for
      female patients with relapsed/refractory GCT.

PMID- 28510617
TI  - miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle
      after acute contusion.
AB  - Growing evidence suggests the importance of microRNAs (miRNAs) in stress
      signaling pathways. Transforming growth factor-beta (TGF-beta) is a potent
      cytokine that promotes the development of skeletal muscle fibrosis after acute
      contusion. However, how miRNAs are involved in TGF-beta signaling and confer the
      robustness of TGF-beta-induced fibrotic response remains to be fully elucidated.
      Here, we demonstrated that miR-146a-5p (miR-146) levels were reduced in a
      fibrotic mouse model after acute muscle contusion. It was also found that TGF
      beta treatment decreased the expression of miR-146 in vitro in a dose- and time
      dependent manner. In addition, overexpression of Smad3 and Samd4, two key players
      in TGF-beta signaling, suppressed the expression of miR-146 in muscle cells.
      Overexpression of miR-146 inhibited the expressions of fibrosis markers both in
      vitro and in vivo. Moreover, increase in the expression of miR-146 in muscle
      cells was able to attenuate the effect of TGF-beta on the expressions of fibrosis
      markers. Mechanistic analysis revealed that Smad4 is a direct target of miR-146
      in muscle cells. Furthermore, the anti-fibrotic effect of miR-146 could be
      blocked by overexpression of Smad4 in vivo. These results suggest that Smad4 is
      down-regulated by miR-146 in skeletal muscle. Taken together, our results
      indicate that the anti-fibrotic miR-146 is a component of TGF-beta signaling. It
      is down-regulated by Smad protein, and can inhibit the expression of Smad4. Our
      study suggests that miR-146 might have a therapeutic potential to reduce skeletal
      muscle fibrosis after injury.

PMID- 28510618
TI  - Auditory Processing of Older Adults With Probable Mild Cognitive Impairment.
AB  - Purpose: Studies suggest that deficits in auditory processing predict cognitive
      decline and dementia, but those studies included limited measures of auditory
      processing. The purpose of this study was to compare older adults with and
      without probable mild cognitive impairment (MCI) across two domains of auditory
      processing (auditory performance in competing acoustic signals and temporal
      aspects of audition). Method: The Montreal Cognitive Assessment (Nasreddine et
      al., 2005) was used to classify participants as with or without probable MCI. In
      this cross-sectional study, participants (n = 79) completed 4 measures of
      auditory processing: Synthetic Sentence Identification with Ipsilateral Competing
      Message (Gates, Beiser, Rees, D'Agostino, & Wolf, 2002), Dichotic Sentence
      Identification (Fifer, Jerger, Berlin, Tobey, & Campbell, 1983), Adaptive Tests
      of Temporal Resolution (ATTR; Lister & Roberts, 2006; across-channel and within
      channel subtests), and time-compressed speech (Wilson, 1993; Wilson, Preece,
      Salamon, Sperry, & Bornstein, 1994). Audiometry was also conducted. Results:
      Those with probable MCI had significantly poorer performance than those without
      MCI on Synthetic Sentence Identification with Ipsilateral Competing Message,
      Dichotic Sentence Identification, and the ATTR within-channel subtest. No group
      differences were found for time-compressed speech, ATTR across-channel, or
      audiometric measures. Conclusions: Older adults with cognitive impairment not
      only have difficulty with competing acoustic signals but may also show poor
      temporal processing. The profile of auditory processing deficits among older
      adults with cognitive impairment may include multiple domains.

PMID- 28510619
TI  - Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory
      Study.
AB  - Background: Previous studies have shown that individuals with diabetes exhibit
      accelerated cognitive decline. However, methodological limitations have limited
      the quality of this evidence. Heterogeneity in study design, cognitive test
      administration, and methods of analysis of cognitive data have made it difficult
      to synthesize and translate findings to practice. We analyzed longitudinal data
      from the Ginkgo Evaluation of Memory Study to test our hypothesis that older
      adults with diabetes have greater test-specific and domain-specific cognitive
      declines compared to older adults without diabetes. Methods: Tests of memory,
      visuo-spatial construction, language, psychomotor speed, and executive function
      were administered. Test scores were standardized to z-scores and averaged to
      yield domain scores. Linear random effects models were used to compare baseline
      differences and changes over time in test and domain scores among individuals
      with and without diabetes. Results: Among the 3,069 adults, aged 72-96 years,
      9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with
      diabetes exhibited greater baseline differences in a test of executive function
      (trail making test, Part B) and greater declines in a test of language (phonemic
      verbal fluency). For the composite cognitive domain scores, participants with
      diabetes exhibited lower baseline executive function and global cognition domain
      scores, but no significant differences in the rate of decline. Conclusions:
      Identifying cognitive domains most affected by diabetes can lead to targeted risk
      modification, possibly in the form of lifestyle interventions such as diet and
      physical activity, which we know to be beneficial for improving vascular risk
      factors, such as diabetes, and therefore may reduce the risk of executive
      dysfunction and possible dementia.

PMID- 28510620
TI  - Association Between Neighborhood Supermarket Presence and Glycated Hemoglobin
      Levels Among Patients With Type 2 Diabetes Mellitus.
AB  - We estimated associations between neighborhood supermarket gain or loss and
      glycemic control (assessed by glycated hemoglobin (HbA1c) values) in patients
      from the Kaiser Permanente Northern California Diabetes Registry (n = 434,806
      person-years; 2007-2010). Annual clinical measures were linked to metrics from a
      geographic information system for each patient's address of longest residence. We
      estimated the association between change in supermarket presence (gain, loss, or
      no change) and change in HbA1c value, adjusting for individual- and area-level
      attributes and according to baseline glycemic control (near normal, <6.5%; good,
      6.5%-7.9%; moderate, 8.0%-8.9%; and poor, >=9.0%). Supermarket loss was
      associated with worse HbA1c trajectories for those with good, moderate, and poor
      glycemic control at baseline, while supermarket gain was associated with
      marginally better HbA1c outcomes only among patients with near normal HbA1c
      values at baseline. Patients with the poorest baseline HbA1c values (>=9.0%) had
      the worst associated changes in glycemic control following either supermarket
      loss or gain. Differences were not clinically meaningful relative to no change in
      supermarket presence. For patients with type 2 diabetes mellitus, gaining
      neighborhood supermarket presence did not benefit glycemic control in a
      substantive way. The significance of supermarket changes on health depends on a
      complex interaction of resident, neighborhood, and store characteristics.

PMID- 28510621
TI  - miR-290 contributes to the low abundance of cyclin D1 protein in mouse embryonic
      stem cells.
AB  - Mouse miR-290 cluster miRNAs are expressed specifically in early embryos and
      embryonic germ cells. These miRNAs play critical roles in the maintenance of
      pluripotency and self-renewal. Here, we showed that Cyclin D1 is a direct target
      gene of miR-290 cluster miRNAs. Negative relationships between the expression of
      Cyclin D1 protein and miR-290 cluster miRNAs in pluripotent and non-pluripotent
      cells, as well as in differentiating CGR8 cells were observed. Inhibition of miR
      290 cluster miRNAs could arrest cells at the G1 phase and slow down the cell
      proliferation in CGR8 mouse stem cells. Since miR-290 cluster miRNAs are the most
      dominant stem-cell-specific miRNAs, our results revealed an important cause for
      the absence of Cyclin D1 in mouse embryonic stem cells.

PMID- 28510622
TI  - Development and validation of a noncontact spectroscopic device for hemoglobin
      estimation at point-of-care.
AB  - Anemia severely and adversely affects human health and socioeconomic development.
      Measuring hemoglobin with the minimal involvement of human and financial
      resources has always been challenging. We describe a translational spectroscopic
      technique for noncontact hemoglobin measurement at low-resource point-of-care
      settings in human subjects, independent of their skin color, age, and sex, by
      measuring the optical spectrum of the blood flowing in the vascular bed of the
      bulbar conjunctiva. We developed software on the LabVIEW platform for automatic
      data acquisition and interpretation by nonexperts. The device is calibrated by
      comparing the differential absorbance of light of wavelength 576 and 600 nm with
      the clinical hemoglobin level of the subject. Our proposed method is consistent
      with the results obtained using the current gold standard, the automated
      hematology analyzer. The proposed noncontact optical device for hemoglobin
      estimation is highly efficient, inexpensive, feasible, and extremely useful in
      low-resource point-of-care settings. The device output correlates with the
      different degrees of anemia with absolute and trending accuracy similar to those
      of widely used invasive methods. Moreover, the device can instantaneously
      transmit the generated report to a medical expert through e-mail, text messaging,
      or mobile apps.

PMID- 28510623
TI  - Sensing of Streptococcus mutans by microscopic imaging ellipsometry.
AB  - Microscopic imaging ellipsometry is an optical technique that uses an objective
      and sensing procedure to measure the ellipsometric parameters ? and ? in the form
      of microscopic maps. This technique is well known for being noninvasive and label
      free. Therefore, it can be used to detect and characterize biological species
      without any impact. Microscopic imaging ellipsometry was used to measure the
      optical response of dried Streptococcus mutans cells on a glass substrate. The
      ellipsometric ? and ? maps were obtained with the Optrel Multiskop system for
      specular reflection in the visible range ( ? = 450 to 750 nm). The ? and ? images
      at 500, 600, and 700 nm were analyzed using three different theoretical models
      with single-bounce, two-bounce, and multibounce light paths to obtain the optical
      constants and height distribution. The obtained images of the optical constants
      show different aspects when comparing the single-bounce analysis with the two
      bounce or multibounce analysis in detecting S. mutans samples. Furthermore, the
      height distributions estimated by two-bounce and multibounce analyses of S.
      mutans samples were in agreement with the thickness values measured by AFM, which
      implies that the two-bounce and multibounce analyses can provide information
      complementary to that obtained by a single-bounce light path.

PMID- 28510624
TI  - Chromatic interocular-switch rivalry.
AB  - Interocular-switch rivalry (also known as stimulus rivalry) is a kind of
      binocular rivalry in which two rivalrous images are swapped between the eyes
      several times a second. The result is stable periods of one image and then the
      other, with stable intervals that span many eye swaps (Logothetis, Leopold, &
      Sheinberg, 1996). Previous work used this close kin of binocular rivalry with
      rivalrous forms. Experiments here test whether chromatic interocular-switch
      rivalry, in which the swapped stimuli differ in only chromaticity, results in
      slow alternation between two colors. Swapping equiluminant rivalrous
      chromaticities at 3.75 Hz resulted in slow perceptual color alternation, with one
      or the other color often continuously visible for two seconds or longer (during
      which there were 15+ eye swaps). A well-known theory for sustained percepts from
      interocular-switch rivalry with form is inhibitory competition between binocular
      neurons driven by monocular neurons with matched orientation tuning in each eye;
      such binocular neurons would produce a stable response when a given orientation
      is swapped between the eyes. A similar model can account for the percepts here
      from chromatic interocular-switch rivalry and is underpinned by the
      neurophysiological finding that color-preferring binocular neurons are driven by
      monocular neurons from each eye with well-matched chromatic selectivity (Peirce,
      Solomon, Forte, & Lennie, 2008). In contrast to chromatic interocular-switch
      rivalry, luminance interocular-switch rivalry with swapped stimuli that differ in
      only luminance did not result in slowly alternating percepts of different
      brightnesses.

PMID- 28510625
TI  - Rethinking ADA signage standards for low-vision accessibility.
AB  - Americans With Disabilities Act (ADA) and International Code Council (ICC)
      standards for accessible buildings and facilities affect design and construction
      of all new and renovated buildings throughout the United States, and form the
      basis for compliance with the ADA. While these standards may result in acceptable
      accessibility for people who are fully blind, they fall far short of what they
      could and should accomplish for those with low vision. In this article I critique
      the standards, detailing their lack of evidence base and other shortcomings. I
      suggest that simply making existing requirements stricter (e.g., by mandating
      larger letter size or higher contrasts) will not ensure visual accessibility and
      therefore cannot act as a valid basis for compliance with the law. I propose two
      remedies. First, requirements for visual characteristics of signs intended to
      improve access for those with low vision should be expressed not in terms of
      physical features, such as character height and contrast, but rather in terms of
      the distance at which a sign can be read by someone with nominally normal (20/20)
      visual acuity under expected lighting conditions for the installed environment.
      This would give sign designers greater choice in design parameters but place on
      them the burden of ensuring legibility. Second, mounting of directional signs,
      which are critical for effective and efficient wayfinding, should be required to
      be in consistent and approachable locations so that those with reduced acuity may
      view them at close distance.

PMID- 28510627
TI  - Erratum.

PMID- 28510626
TI  - Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the
      Intronic Mutation in the CEP290 Gene.
AB  - Purpose: To determine efficacy outcome measures for clinical trials of Leber
      congenital amaurosis (LCA) associated with a common intronic mutation in the
      CEP290 gene. Methods: CEP290-LCA patients (ages 5-48) with the intronic mutation
      (c.2991+1655A>G) were studied as a retrospective observational case series using
      clinical methods and with full-field sensitivity testing (FST), optical coherence
      tomography (OCT), autofluorescence imaging (NIR-RAFI), transient pupillary light
      reflex (TPLR), oculomotor control and instability (OCI), a mobility course, and a
      questionnaire (NEI-VFQ). Patients were investigated cross-sectionally but a
      subset was able to be followed longitudinally. Results: With FST, there was no
      rod function; cone sensitivities had a wide range from not detectable to near
      normal. OCT analyses indicated retained central photoreceptors with abnormal
      distal laminae. Based on OCT and FST, most patients had dissociation of structure
      and function. TPLR was nondetectable in the majority of patients, with responders
      demonstrating severe losses in light sensitivity. OCI was abnormal in most
      patients. NEI-VFQ scores had a similar range to those of other severe
      retinopathies. Mobility scores were consistent with FST sensitivities. In
      patients examined with FST, OCT, and NIR-RAFI over long-term intervals (7-10
      years), there was limited but detectable disease progression. Conclusions:
      Efficacy would be a quantitative change in foveal cone function and possibly
      distal laminar structure. FST provides a subjective photoreceptor-based outcome;
      OCT and NIR-RAFI can assess photoreceptor and RPE structure. TPLR and OCI can
      provide objective measures of postretinal transmission. Minimal change over a
      decade indicates that there is no practical value in natural history studies.

PMID- 28510628
TI  - Erratum.

PMID- 28510630
TI  - Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An
      Integrative Approach.
AB  - Purpose: To review the usefulness of local and systemic inflammatory biomarkers
      of diabetic retinopathy (DR) to implement a more personalized treatment. Methods:
      An integrated research (from ophthalmologist and diabetologist point of view) of
      most significant literature on serum, vitreous, and aqueous humor (AH)
      biochemical biomarkers related to inflammation at early and advanced stages of DR
      (including diabetic macular edema [DME] and proliferative DR) was performed.
      Moreover, novel imaging retinal biomarkers of local "inflammatory condition" were
      described. Results: Multiple inflammatory cytokines and chemokines are increased
      in DR in both serum as well as in the eye (vitreous and AH). Nevertheless, local
      rather than systemic production of proinflammatory cytokines seems more relevant
      in the pathogenesis of both DR and DME. In the eye, retinal glia cells (macroglia
      and microglia) together with RPE are major sources of proinflammatory and
      angiogenic modulators. Retinal imaging allows for noninvasive clinical evaluation
      of retinal inflammatory response induced by diabetes mellitus. Conclusions:
      Proinflammatory cytokines/chemokines play an essential role in the pathogenesis
      of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing
      inflammation have emerged as useful tools for monitoring the onset and
      progression of DR. In addition, "liquid biopsy" of AH seems a good option in
      patients with advanced stages of DR requiring intravitreous injections. This
      strategy may permit us to implement a more personalized treatment with better
      visual function outcome. Further evaluation and validation of circulating and
      local biomarkers, as well as multimodal imaging is needed to gain new insights
      into this issue.

PMID- 28510629
TI  - Fibroblast Growth Factor Receptor 2 (FGFR2) Is Required for Meibomian Gland
      Homeostasis in the Adult Mouse.
AB  - Purpose: Little is known about the signaling mechanisms controlling meibomian
      gland (MG) homeostasis and the pathogenic processes leading to MG atrophy and
      dysfunction in dry eye disease (DED). We investigated the role of fibroblast
      growth factor receptor 2 (FGFR2) in the MG homeostasis of adult mice. Methods: A
      triple transgenic mouse strain (Krt14-rtTA; tetO-Cre; Fgfr2flox/flox), referred
      to as Fgfr2CKO mice, was generated in which the Fgfr2 gene is ablated by Cre
      recombinase in keratin 14 (Krt14)-expressing epithelial cells on doxycycline
      (Dox) induction. FGFR2 expression in normal human and mouse MGs was evaluated by
      immunohistochemistry. Pathologic MG changes in transgenic mice with conditional
      deletion of FGFR2 were examined by lipid staining, histology, and immunostaining.
      Results: FGFR2 was highly expressed in normal human MGs and adult mouse MGs. Two
      month-old Fgfr2CKO mice fed Dox-containing chow for 2 weeks developed severe MG
      atrophy. MG acinar atrophy in the Fgfr2CKO mice was associated with reduced lipid
      (meibum) production and the development of clinical findings similar to those in
      humans with evaporative DED related to MG dysfunction (MGD). Immunohistochemical
      analyses showed that FGFR2 deletion severely affected proliferation and
      differentiation of MG acinar cells but affected MG ductal cells to a lesser
      extent. Conclusions: FGFR2 deletion results in significant MG acinar atrophy and
      clinical manifestations of MGD in Fgfr2CKO mice, suggesting that MG homeostasis
      is FGFR2 dependent. The Fgfr2CKO mice with inducible MG atrophy can serve as a
      valuable animal model for investigating the pathogenesis of MGD and developing
      novel therapeutic strategies for MGD-related DED.

PMID- 28510632
TI  - Hepatitis C Virus Relapse 78 Weeks After Completion of Successful Direct-Acting
      Therapy.

PMID- 28510631
TI  - How might edaphic specialists in gypsum islands respond to climate change?
      Reciprocal sowing experiment to infer local adaptation and phenotypic plasticity.
AB  - Background and Aims: Local adaptation and phenotypic plasticity are considered
      key mechanisms for coping with climate warming, especially for plant species that
      inhabit island-like habitats. In Spain a complete guild of edaphic specialists,
      most of them threatened, occurs in gypsum outcrops, but how these species will
      respond to climate change has received little attention. Methods: A reciprocal
      sowing experiment was performed to determine the extent of local adaptation and
      phenotypic plasticity in five gypsophytes with contrasting distributions along a
      climate gradient. Germination, seedling growth and survival were recorded during
      a 4-year period. Key Results: Plants responded plastically according to their
      positions along the regional climate gradient, as well as locally between matched
      locations. All species exhibited highly plastic responses and stress-tolerant
      behaviours, especially in terms of seedling survival during summer drought.
      However, no evidence of local adaptation was detected in any of the locations,
      where local individuals never performed better than those from other sites. In
      some sites, both germination and seedling recruitment were higher irrespective of
      parent plant origin. Conclusions: The lack of local adaptation to drought
      displayed at the regeneration stage indicates limited capacity for in situ
      genetic response to new climate scenarios. Nevertheless, a plastic response along
      the climatic gradient does suggest a wider species-level capacity to enable these
      edaphic specialists to cope with increasing aridity over coming decades.

PMID- 28510634
TI  - Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.
AB  - Background: Autologous collagen is an ideal soft tissue filler and may serve as a
      matrix for stem cell implantation and growth. Procurement of autologous collagen
      has been limited, though, secondary to a sufficient source. Liposuction is a
      widely performed and could be a source of autologous collagen. Objectives: The
      amount of collagen and its composition in liposuctioned fat remains unknown. The
      purpose of this research was to characterize an adipose-derived tissue-based
      product created using ultrasonic cavitation and cryo-grinding. This study
      evaluated the cellular and protein composition of the final product. Methods: Fat
      was obtained from individuals undergoing routine liposuction and was processed by
      a 2 step process to obtain only the connective tissue. The tissue was then
      evaluated by scanning electronic microscope, Western blot analysis, and flow
      cytometry. Results: Liposuctioned fat was obtained from 10 individuals with an
      average of 298 mL per subject. After processing an average of 1 mL of collagen
      matrix was obtained from each 100 mL of fat. Significant viable cell markers were
      present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ >
      CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other
      proteins. Scanning electronic microscope study showed a regular pattern of cross
      linked, helical collagen. Additionally, vital staing demonstrated that the cells
      were still viable after processing. Conclusions: Collagen and cells can be easily
      obtained from liposuctioned fat by ultrasonic separation without alteration of
      the overall cellular composition of the tissue. Implantation results in new
      collagen and cellular growth. Collagen matrix with viable cells for autologous
      use can be obtained from liposuctioned fat and may provide long term results.
      Level of Evidence: 5.

PMID- 28510635
TI  - Arterial Blood Pressure and Lifestyle Variability: In Quest of a Comprehensive
      Approach.

PMID- 28510633
TI  - Obesity and Diabetes as Risk Factors for Severe Plasmodium falciparum Malaria:
      Results From a Swedish Nationwide Study.
AB  - Background: Noncommunicable diseases and obesity are increasing in prevalence
      globally, also in populations at risk of malaria. We sought to investigate if
      comorbidity, in terms of chronic diseases and obesity, is associated with severe
      Plasmodium falciparum malaria. Methods: We performed a retrospective
      observational study in adults (>=18 years of age) diagnosed with malaria in
      Sweden between January 1995 and May 2015. We identified cases through the
      surveillance database at the Public Health Agency of Sweden and reviewed clinical
      data from 18 hospitals. Multivariable logistic regression was used to assess
      associations between comorbidities and severe malaria. Results: Among 937 adults
      (median age, 37 years; 66.5% were male), patients with severe malaria had higher
      prevalence of chronic diseases (28/92 [30.4%]) compared with nonsevere cases
      (151/845 [17.9%]) (P = .004). Charlson comorbidity score >=1 was associated with
      severe malaria (adjusted odds ratio [aOR], 2.63 [95% confidence interval {CI},
      1.45-4.77), as was diabetes among individual diagnoses (aOR, 2.98 [95% CI, 1.25
      7.09]). Median body mass index was higher among severe (29.3 kg/m2) than
      nonsevere cases (24.7 kg/m2) (P < .001). Obesity was strongly associated with
      severe malaria, both independently (aOR, 5.58 [95% CI, 2.03-15.36]) and in
      combination with an additional metabolic risk factor (hypertension, dyslipidemia,
      or diabetes) (aOR, 6.54 [95% CI, 1.87-22.88]). The associations were observed
      among nonimmune travelers as well as immigrants from endemic areas. Conclusions:
      Comorbidities, specifically obesity and diabetes, are previously unidentified
      risk factors for severe malaria in adults diagnosed with P. falciparum.
      Noncommunicable diseases should be considered in the acute management and
      prevention of malaria.

PMID- 28510637
TI  - Telomeres, Nutrition, and Longevity: Can We Really Navigate Our Aging?
AB  - Telomeres are dynamic chromosome-end structures that serve as guardians of genome
      stability. They are known to be one of the major determinants of aging and
      longevity in higher mammals. Studies have demonstrated a direct correlation
      between telomere length and life expectancy, stress, DNA damage, and onset of
      aging-related diseases. This review discusses the most important factors that
      influence our telomeres. Various genetic and environmental factors such as diet,
      physical activity, obesity, and stress are known to influence health and
      longevity as well as telomere dynamics. Individuals currently have the
      opportunity to modulate the dynamics of their aging and health span, monitor
      these processes, and even make future projections by following their telomere
      dynamics. As telomeres react to positive as well as negative health factors, we
      should be able to directly influence our telomere metabolism, slow their
      deterioration, and diminish our aging and perhaps extend our life and health
      span.

PMID- 28510636
TI  - Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of
      Resistance Arteries: A Role for Mitochondria.
AB  - Impaired blood flow to peripheral tissues during advanced age is associated with
      endothelial dysfunction and diminished bioavailability of nitric oxide (NO).
      However, it is unknown whether aging impacts coupling between intracellular
      calcium ([Ca2+]i) signaling and small- and intermediate K+ channel (SKCa/IKCa)
      activity during endothelium-derived hyperpolarization (EDH), a signaling pathway
      integral to dilation of the resistance vasculature. To address the potential
      impact of aging on EDH, Fura-2 photometry and intracellular recording were
      applied to evaluate [Ca2+]i and membrane potential of intact endothelial tubes
      (width, 60 um; length, 1-3 mm) freshly isolated from superior epigastric arteries
      of young (4-6 mo) and old (24-26 mo) male C57BL/6 mice. In response to
      acetylcholine, intracellular release of Ca2+ from the endoplasmic reticulum (ER)
      was enhanced with aging. Further, treatment with the mitochondrial uncoupler FCCP
      evoked a significant increase of [Ca2+]i with membrane hyperpolarization in an
      SKCa/IKCa-dependent manner in the endothelium of old but not young mice. We
      conclude that the ability of resistance artery endothelium to release Ca2+ from
      intracellular stores (ie, ER and mitochondria) and hyperpolarize Vm via SKCa/IKCa
      activation is augmented as compensation for reduced NO bioavailability during
      advanced age.

PMID- 28510638
TI  - alpha-Asarone suppresses the proliferation and migration of ASMCs through
      targeting the lncRNA-PVT1/miR-203a/E2F3 signal pathway in RSV-infected rats.
AB  - Asthma is a chronic inflammatory pulmonary disease and respiratory syncytial
      virus (RSV) infection is a common cause of lower respiratory tract illness in
      infants and young children. alpha-Asarone presents many pharmacological effects
      and has been demonstrated to be useful in treating asthma. However, the
      functional mechanism of alpha-asarone in RSV-infected asthma has not been
      investigated. Long non-coding RNAs (lncRNAs) have been reported to play critical
      roles in many biological processes. Although many lncRNAs have been
      characterized, few were reported in asthma, especially in RSV-induced asthma.
      Currently, a novel post-transcriptional regulation has been proposed in which
      lncRNAs function as competing endogenous RNAs (ceRNAs) to competitively sponge
      miRNAs, thereby regulating the target genes. In the present study, we established
      an RSV-infected Sprague-Dawley rat model and demonstrated that lncRNA-PVT1 is
      involved in the mechanism of alpha-asarone in treating RSV-induced asthma, and
      lncRNA-PVT1 regulates the expression of E2F3 by functioning as a ceRNA which
      competitively sponges miR-203a.

PMID- 28510640
TI  - Increased risk of premature death following teenage abortion and childbirth-a
      longitudinal cohort study.
AB  - Background: Teenage pregnancy is associated with an increased risk of premature
      death. However, it is not known whether the outcome of pregnancy, i.e. induced
      abortion or childbirth, affects this risk. Methods: A Finnish population-based
      register study involving a cohort of 13 691 nulliparous teenagers who conceived
      in 1987-89; 6652 of them underwent induced abortion and 7039 delivered. The
      control group consisted of 41 012 coeval women without teenage pregnancy. Follow
      up started at the end of pregnancy and lasted until 6th June 2013. Results: Women
      with teenage pregnancy had a higher risk of overall mortality vs. controls
      (mortality rate ratio [MRR] 1.6, [95% CI 1.4-1.8]) and were more likely to die
      prematurely as a result of suicide, alcohol-related causes, circulatory diseases
      and motor vehicle accidents. A low educational level appeared to explain these
      excess risks, except for suicide (adj. MRR 1.5, [95% CI 1.1-2.0]). After
      adjusting for confounders, the childbirth group faced lower risks of suicide
      (adj. MRR 0.5, [95% CI 0.3-0.9]) and dying from injury and poisoning (adj. MRR
      0.6, [95% CI 0.4-0.8]) compared with women who had undergone abortion.
      Conclusions: A low educational level is associated with the increased risk of
      premature death among women with a history of teenage pregnancy, except for
      suicide. Extra efforts should be made to encourage pregnant teenagers to continue
      education, and to provide psychosocial support to teenagers who undergo induced
      abortion.

PMID- 28510641
TI  - Community-level football injury epidemiology: traumatic injuries treated at
      Swedish emergency medical facilities.
AB  - Background: Despite the popularity of the sport, few studies have investigated
      community-level football injury patterns. This study examines football injuries
      treated at emergency medical facilities using data from three Swedish counties.
      Methods: An open-cohort design was used based on residents aged 0-59 years in
      three Swedish counties (pop. 645 520). Data were collected from emergency medical
      facilities in the study counties between 1 January 2007 and 31 December 2010.
      Injury frequencies and proportions for age groups stratified by sex were
      calculated with 95% confidence intervals (95% CIs) and displayed per diagnostic
      group and body location. Results: Each year, more than 1/200 person aged 0-59
      years sustained at least one injury during football play that required emergency
      medical care. The highest injury incidence was observed among adolescent boys
      [2009 injuries per 100 000 population years (95% CI 1914-2108)] and adolescent
      girls [1413 injuries per 100 000 population years (95% CI 1333-1498)]. For female
      adolescents and adults, knee joint/ligament injury was the outstanding injury
      type (20% in ages 13-17 years and 34% in ages 18-29 years). For children aged 7
      12 years, more than half of the treated injuries involved the upper extremity;
      fractures constituted about one-third of these injuries. Conclusions: One of
      every 200 residents aged 0-59 years in typical Swedish counties each year
      sustained a traumatic football injury that required treatment in emergency
      healthcare. Further research on community-level patterns of overuse syndromes
      sustained by participation in football play is warranted.

PMID- 28510639
TI  - Toward an elucidation of the molecular genetics of inherited retinal
      degenerations.
AB  - While individually classed as rare diseases, hereditary retinal degenerations
      (IRDs) are the major cause of registered visual handicap in the developed world.
      Given their hereditary nature, some degree of intergenic heterogeneity was
      expected, with genes segregating in autosomal dominant, recessive, X-linked
      recessive, and more rarely in digenic or mitochondrial modes. Today, it is
      recognized that IRDs, as a group, represent one of the most genetically diverse
      of hereditary conditions - at least 260 genes having been implicated, with 70
      genes identified in the most common IRD, retinitis pigmentosa (RP). However,
      targeted sequencing studies of exons from known IRD genes have resulted in the
      identification of candidate mutations in only approximately 60% of IRD cases.
      Given recent advances in the development of gene-based medicines,
      characterization of IRD patient cohorts for known IRD genes and elucidation of
      the molecular pathologies of disease in those remaining unresolved cases has
      become an endeavor of the highest priority. Here, we provide an outline of
      progress in this area.

PMID- 28510642
TI  - Ageism in Health Care: A Systematic Review of Operational Definitions and
      Inductive Conceptualizations.
AB  - Purpose: International and national bodies have identified tackling ageism in
      health care as an urgent goal. However, health professionals, researchers, and
      policy makers recognize that it is not easy to identity and fight ageism in
      practice, as the identification of multiple manifestations of ageism is dependent
      on the way it is defined and operationalized. This article reports on a
      systematic review of the operational definitions and inductive conceptualizations
      of ageism in the context of health care. Design and Methods: We reviewed
      scientific articles published from January 1995 to June 2015 and indexed in the
      electronic databases Web of Science, PubMed, and Cochrane. Electronic searches
      were complemented with visual scanning of reference lists and hand searching of
      leading journals in the field of ageing and social gerontology. Results: The
      review reveals that the predominant forms of operationalization and inductive
      conceptualization of ageism in the context of health care have neglected some
      components of ageism, namely the self-directed and implicit components.
      Furthermore, the instruments used to measure ageism in health care have as
      targets older people in general, not older patients in particular. Implications:
      The results have important implications for the advancement of research on this
      topic, as well as for the development of interventions to fight ageism in
      practice. There is a need to take into account underexplored forms of
      operationalization and inductive conceptualizations of ageism, such as self
      directed ageism and implicit ageism. In addition, ageism in health care should be
      measured by using context-specific instruments.

PMID- 28510643
TI  - How to Face the Outbreak of Viral Hepatitis A in Men Who Have Sex With Men in
      France Without Vaccines?

PMID- 28510644
TI  - Temporal trends in acute myocardial infarction presentation and association with
      use of cardioprotective drugs: a nationwide registry-based study.
AB  - Aim: The present study aimed to investigate temporal trends in myocardial
      infarction (MI) presentation with or without ST-segment elevation and the
      association with the use of cardioprotective drugs prior to admission. Methods
      and results: Using individual-level linkage of data from Danish nationwide
      registries, we identified all patients 30 years or older admitted with a first
      time MI in the period 2003-2012, and their use of cardioprotective drugs 6 months
      prior to admission. We calculated incidence rates per 100 000 person-years (IRs)
      of ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI). We identified 22 247
      patients admitted with STEMI and 50 403 with NSTEMI. IRs for NSTEMI decreased by
      35% from 194 in 2003 to 126 in 2012, whereas IRs for STEMI peaked in 2007 and
      subsequently declined from 71 to 65. Preadmission use of cardioprotective drugs
      increased in both groups from 2003 to 2012. Patients admitted with STEMI had odds
      ratio (OR) 0.64 [95% confidence interval (CI) 0.61-0.67] for preadmission use of
      aspirin compared with patients admitted with NSTEMI. Corresponding ORs were 0.82
      (CI 0.78-0.87) for statins, 0.87 (CI 0.82-0.91) for beta-blockers, 0.89 (CI 0.85
      0.92) for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,
      and 0.52 (CI 0.44-0.61) for thienopyridines. Also, 30-day and 1-year mortality
      declined in patients both admitted with STEMI and NSTEMI. Conclusion: The IRs of
      MI declined between 2003 and 2012, primarily driven by a 35% reduction in IRs for
      NSTEMI whereas IRs for STEMI declined after 2007. Preadmission use of
      cardioprotective drugs increased markedly and was associated with lower ORs of
      presenting with STEMI than NSTEMI.

PMID- 28510645
TI  - Nurse interventions to improve medication adherence among discharged older
      adults: a systematic review.
AB  - Background: discharged older adult inpatients are often prescribed numerous
      medications. However, they only take about half of their medications and many
      stop treatments entirely. Nurse interventions could improve medication adherence
      among this population. Objective: to conduct a systematic review of trials that
      assessed the effects of nursing interventions to improve medication adherence
      among discharged, home-dwelling and older adults. Method: we conducted a
      systematic review according to the methods in the Cochrane Collaboration Handbook
      and reported results according to the PRISMA statement. We searched for
      controlled clinical trials (CCTs) and randomised CCTs (RCTs), published up to 8
      November 2016 (using electronic databases, grey literature and hand searching),
      that evaluated the effects of nurse interventions conducted alone or in
      collaboration with other health professionals to improve medication adherence
      among discharged older adults. Medication adherence was defined as the extent to
      which a patient takes medication as prescribed. Results: out of 1,546 records
      identified, 82 full-text papers were evaluated and 14 studies were included-11
      RCTs and 2 CCTs. Overall, 2,028 patients were included (995 in intervention
      groups; 1,033 in usual-care groups). Interventions were nurse-led in seven
      studies and nurse-collaborative in seven more. In nine studies, adherence was
      higher in the intervention group than in the usual-care group, with the
      difference reaching statistical significance in eight studies. There was no
      substantial difference in increased medication adherence whether interventions
      were nurse-led or nurse-collaborative. Four of the 14 studies were of relatively
      high quality. Conclusion: nurse-led and nurse-collaborative interventions
      moderately improved adherence among discharged older adults. There is a need for
      large, well-designed studies using highly reliable tools for measuring medication
      adherence.

PMID- 28510646
TI  - Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the
      TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized
      study.
AB  - Aims: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant
      ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However,
      both drugs are associated with an increase in bleeding complications. The
      objective of the present study was to evaluate the benefit of switching dual
      antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin
      plus clopidogrel 1 month after ACS. Methods and results: We performed an open
      label, monocentric, and randomized trial. From March 2014 to April 2016, patients
      admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12
      blocker and without adverse event at 1 month, were assigned to switch to aspirin
      and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged
      DAPT). The primary outcome was a composite of cardiovascular death, urgent
      revascularization, stroke and bleeding as defined by the Bleeding Academic
      Research Consortium (BARC) classification >=2 at 1 year post ACS. Six hundred and
      forty six patients were randomized and 645 analysed, corresponding to 322
      patients in the switched DAPT and 323 in the unchanged DAPT group. The primary
      endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85
      (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No
      significant differences were reported on ischaemic endpoints, while BARC >= 2
      bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in
      the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). Conclusion: A
      switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding
      complications without increase in ischaemic events following ACS.

PMID- 28510647
TI  - Epicardial cardioverter-defibrillator implantation in a 4-month-old infant
      bridged to heart transplantation.
AB  - Implantable cardioverter-defibrillator (ICD) is the gold standard therapy for the
      prevention of sudden cardiac death. Nevertheless, ICD placement in the paediatric
      population is still limited because of several technical difficulties. Several
      implantation techniques have been proposed but experience in infants with very
      low weight and less than 6 months is very limited. We herein describe a case of a
      minimally invasive ICD epicardial implantation in a 4-month-old infant weighing 5
      kg. A diagnosis of arrhythmic cardiomyopathy with left ventricular non-compaction
      disease with ventricular tachycardia storms, QT prolongation and Wolff-Parkinson
      White pattern was made. Antiarrhythmic drugs, radiofrequency ablation and
      sympathetic denervation were not effective. ICD implantation was successful
      allowing the infant to survive and bridging to heart transplantation.

PMID- 28510648
TI  - Commentary on: Functional and Volumetric Analysis of the Pectoralis Major Muscle
      After Submuscular Breast Augmentation.

PMID- 28510649
TI  - The Orbital Septum in Upper Eyelid Retraction and Ptosis Complicating Fat
      Injection.

PMID- 28510651
TI  - Spotlight on... Jeff Errington.

PMID- 28510650
TI  - To Get the Best Outcome, Choose the Best Outcome.

PMID- 28510652
TI  - International migrants' use of emergency departments in Europe compared with non
      migrants' use: a systematic review.
AB  - Background: International migration across Europe is increasing. High rates of
      net migration may be expected to increase pressure on healthcare services,
      including emergency services. However, the extent to which immigration creates
      additional pressure on emergency departments (EDs) is widely debated. This review
      synthesizes the evidence relating to international migrants' use of EDs in
      European Economic Area (EEA) countries as compared with that of non-migrants.
      Methods: MEDLINE, EMBASE, CINAHL, The Cochrane Library and The Web of Science
      were searched for the years 2000-16. Studies reporting on ED service utilization
      by international immigrants, as compared with non-migrants, were eligible for
      inclusion. Included studies were restricted to those conducted in EEA countries
      and English language publications only. Results: Twenty-two articles (from six
      host countries) were included. Thirteen of 18 articles reported higher volume of
      ED service use by immigrants, or some immigrant sub-groups. Migrants were seen to
      be significantly more likely to present to the ED during unsocial hours and more
      likely than non-migrants to use the ED for low-acuity presentations. Differences
      in presenting conditions were seen in 4/7 articles; notably a higher rate of
      obstetric and gynaecology presentations among migrant women. Conclusions: The
      principal finding of this review is that migrants utilize the ED more, and
      differently, to the native populations in EEA countries. The higher use of the ED
      for low-acuity presentations and the use of the ED during unsocial hours suggest
      that barriers to primary healthcare may be driving the higher use of these
      emergency services although further research is needed.

PMID- 28510654
TI  - Asn-linked oligosaccharide chain of a crenarchaeon, Pyrobaculum calidifontis, is
      reminiscent of the eukaryotic high-mannose-type glycan.
AB  - Pyrobaculum calidifontis is a hyperthermophilic archaeon that belongs to the
      phylum Crenarchaeota. In contrast to the phylum Euryarchaeota, only the N-glycan
      structure of the genus Sulfolobus is known in Crenarchaeota. Here, we enriched
      glycoproteins from cultured P. calidifontis cells, by ConA lectin chromatography.
      The MASCOT search identified proteins with at least one potential N-glycosylation
      site. The MS/MS analysis of twelve small tryptic glycopeptides confirmed the
      canonical N-glycosylation consensus in P. calidifontis. We determined the N
      linked oligosaccharide structure produced by an in vitro enzymatic oligosaccharyl
      transfer reaction. P. calidifontis cells were cultured in rich medium
      supplemented with 13C-glucose, for the metabolic labeling of N-oligosaccharide
      donors. An incubation with a synthetic peptide substrate produced glycopeptides
      with isotopically labeled oligosaccharide moieties. The MS and NMR analysis
      revealed that the P. calidifontis N-glycan has a biantennary, high-mannose-type
      structure consisting of up to 11 monosaccharide residues. The base portion of the
      P. calidifontis N-glycan strongly resembles the eukaryotic core structure, alpha
      Man-(1-3)-(alpha-Man-(1-6)-)beta-Man-(1-4)-beta-GlcNAc-(1-4)-beta-GlcNAc-Asn.
      Structural differences exist in the anomeric configuration between Man and
      GlcNAc, and the chitobiose structure is chemically modified: one GlcNAc residue
      is oxidized to glucoronate, and the GlcNAc residues are both modified with an
      additional acetamido group at the C-3 position. As a result, the core structure
      of the P. calidifontis N-glycan is alpha-Man-(1-3)-(alpha-Man-(1-6)-)alpha-Man-(1
      4)-beta-GlcANAc3NAc-(1-4)-beta-GlcNAc3NAc-Asn, in which the unique features of
      the P. calidifontis N-glycan are underlined. In spite of these differences, the
      structure of the P. calidifontis N-glycan is the most similar to the eukaryotic
      counterparts, among all archaeal N- glycans reported to date.

PMID- 28510656
TI  - Associations of Environmental Factors With Quality of Life in Older Adults.
AB  - Purpose of the Study: Environmental factors play an important role in the quality
      of life of older people who often have difficulty maintaining physical,
      psychological, and social functioning. In this study, we aimed at (a) developing
      a measurement instrument assessing the factors of older adults' perceptions of
      their environment, (b) examining the associations of these environmental factors
      with quality of life domains physical health, psychological, social relations,
      and environmental, controlling for background characteristics. Design and
      Methods: Associations between environmental factors and quality of life domains
      were examined in a cross-sectional study using a sample of 1,031 Dutch people
      aged 65 years and older. Participants completed a Web-based questionnaire, the
      "Senioren Barometer." Forty-two questions on environmental factors were asked,
      and quality of life domains were assessed by the WHOQOL-BREF. Results: Seven
      scales (comprising 3-9 items) of environment were constructed-housing,
      facilities, nuisance, residents, neighborhood, stench/noise, and traffic. All
      quality of life domains (physical, psychological, social, environmental) were
      associated with at least one environmental scale. Housing, residents, and
      nuisance were associated with 4, 3, and 2 domains, respectively. Facilities,
      neighborhood, stench/noise, and traffic were associated only with quality of life
      environmental. Implications: This study showed that multiple environmental
      factors are associated with quality of life in older people. To support
      independent living in older people health and social care professionals and
      policymakers may need to carry out interventions, in particular focusing on
      housing, residents, and nuisance.

PMID- 28510653
TI  - Chronic Corticosterone Treatment During Adolescence Has Significant Effects on
      Metabolism and Skeletal Development in Male C57BL6/N Mice.
AB  - Glucocorticoids are potent modulators of metabolic and behavioral function. Their
      role as mediators in the "stress response" is well known, but arguably their
      primary physiological function is in the regulation of cellular and organismal
      metabolism. Disruption of normal glucocorticoid function is linked to metabolic
      disease, such as Cushing syndrome. Glucocorticoids are also elevated in many
      forms of obesity, suggesting that there are bidirectional effects of these potent
      hormones on metabolism and metabolic function. Adolescence is a time of rapid
      physical growth, and disruptions during this critical time likely have important
      implications for adult function. The hypothalamic-pituitary-adrenal axis
      continues to mature during this period, as do tissues that respond to
      glucocorticoids. In this work, we investigate how chronic noninvasive exposure to
      corticosterone affects metabolic outcomes (body weight, body composition,
      insulin, and glucose homeostasis), as well as changes in bone density in both
      adult and adolescent male mice. Specifically, we report a different pattern of
      metabolic effects in adolescent mice compared with adults, as well as an altered
      trajectory of recovery in adolescents and adults. Together, these data indicate
      the profound influence that adolescent development has on the metabolic outcomes
      of chronic corticosterone exposure, and describe a tractable model for
      understanding the short- and long-term impacts of hypercortisolemic states on
      physiological and neurobehavioral functions.

PMID- 28510655
TI  - miR-145 promoted anoikis resistance in tumor endothelial cells.
AB  - Tumor progression is dependent on tumor angiogenesis. We previously reported that
      the phenotype of tumor endothelial cells (TECs) is distinct from normal
      endothelial cells (NECs). Herein, we conducted a pathway analysis using a public
      TEC microarray database and identified several putative TEC-specific miRNAs. We
      found that miR-145 expression was upregulated in TECs and that miR-145 enhanced
      cell adhesion and anoikis resistance and upregulated Bcl-2 and Bcl-xl via ERK1/2
      in human microvascular endothelial cells. These findings suggested that miR-145
      is involved in the acquisition of the TEC phenotype, partially. Therefore, miR
      145 and its target genes may be molecular targets for anti-angiogenic therapy.

PMID- 28510657
TI  - Heteroblasty in epiphytic bromeliads: functional implications for species in
      understorey and exposed growing sites.
AB  - Background and Aims: The functional relevance of heteroblasty, an abrupt
      morphological change in the ontogeny of a considerable number of angiosperm
      species, is still largely unresolved. During the ontogeny of many epiphytic
      Tillandsioids (Bromeliaceae), such a change occurs when small individuals
      transform into larger, tank-forming individuals that are capable of external
      water storage. Apart from its fundamental effect on plant water relations, the
      associated transition from narrow to broader leaves also affects plant
      architecture. The morphological changes and their effect on light interception
      may be especially relevant for heteroblastic species in the moist understorey,
      which are expected to be limited primarily by light. Methods: A functional
      structural plant model (Yplant) was used to construct digital replicas of
      atmospheric and tank-forming individuals of four species, two of them naturally
      growing in exposed conditions and two occurring in understorey sites. This
      allowed the determination of leaf display efficiencies as well as a systematic
      analysis of leaf architectural traits and their effect on light interception. Key
      Results: Modifying existing plant morphologies showed that broader leaves cause
      more self-shading within the plant. This supports the hypothesis that species
      from the light-limited understorey benefit from the early atmospheric life form
      through increased light capture. Modelling plant morphology that continuously
      followed the ontogenetic trajectories of the leaf architectural traits revealed
      that the rising total leaf number in atmospheric individuals constantly increased
      self-shading. Therefore, at a certain ontogenetic stage, a tipping point was
      reached when the tank form was even favourable in terms of light capture as it
      was associated with fewer leaves. Conclusions: The effects of changes in leaf
      morphology and leaf architecture on plant light capture may explain the common
      occurrence of heteroblastic species in the understorey of Neotropical forests,
      which does not negate a simultaneous positive effect of heteroblasty on plant
      water relations.

PMID- 28510659
TI  - Omission in Text.

PMID- 28510658
TI  - Data Error.

PMID- 28510661
TI  - Tardive Dyskinesia Drug Approved.

PMID- 28510660
TI  - Cardiovascular Mortality Differences-Place Matters.

PMID- 28510662
TI  - Digitized Surgical Slides.

PMID- 28510663
TI  - A First in HCV Drugs for Youths.

PMID- 28510664
TI  - Trends in Use of Sedation for Low-Risk Endoscopy: Looking Beyond Monitored
      Anesthesia Care.

PMID- 28510665
TI  - Antithrombotic Therapy for Venous Thromboembolic Disease.

PMID- 28510667
TI  - Hunger, Health, and Compassion.

PMID- 28510668
TI  - The Supply of Doctors.

PMID- 28510669
TI  - Postoperative Opioid Prescribing and the Pain Scores on Hospital Consumer
      Assessment of Healthcare Providers and Systems Survey.

PMID- 28510671
TI  - Global Burden of Disease Attributable to Hypertension.

PMID- 28510670
TI  - Associations Between Hospital Characteristics, Measure Reporting, and the Centers
      for Medicare & Medicaid Services Overall Hospital Quality Star Ratings.

PMID- 28510672
TI  - Intubation During In-Hospital Cardiac Arrest.

PMID- 28510673
TI  - Legal Ramifications of Ambiguous Clinical Guidelines.

PMID- 28510674
TI  - Global Burden of Disease Attributable to Hypertension-Reply.

PMID- 28510675
TI  - Intubation During In-Hospital Cardiac Arrest-Reply.

PMID- 28510676
TI  - Legal Ramifications of Ambiguous Clinical Guidelines-Reply.

PMID- 28510677
TI  - Drugs for Head Lice.

PMID- 28510678
TI  - Trends and Patterns of Geographic Variation in Cardiovascular Mortality Among US
      Counties, 1980-2014.
AB  - Importance: In the United States, regional variation in cardiovascular mortality
      is well-known but county-level estimates for all major cardiovascular conditions
      have not been produced. Objective: To estimate age-standardized mortality rates
      from cardiovascular diseases by county. Design and Setting: Deidentified death
      records from the National Center for Health Statistics and population counts from
      the US Census Bureau, the National Center for Health Statistics, and the Human
      Mortality Database from 1980 through 2014 were used. Validated small area
      estimation models were used to estimate county-level mortality rates from all
      cardiovascular diseases, including ischemic heart disease, cerebrovascular
      disease, ischemic stroke, hemorrhagic stroke, hypertensive heart disease,
      cardiomyopathy, atrial fibrillation and flutter, rheumatic heart disease, aortic
      aneurysm, peripheral arterial disease, endocarditis, and all other cardiovascular
      diseases combined. Exposures: The 3110 counties of residence. Main Outcomes and
      Measures: Age-standardized cardiovascular disease mortality rates by county,
      year, sex, and cause. Results: From 1980 to 2014, cardiovascular diseases were
      the leading cause of death in the United States, although the mortality rate
      declined from 507.4 deaths per 100 000 persons in 1980 to 252.7 deaths per 100
      000 persons in 2014, a relative decline of 50.2% (95% uncertainty interval [UI],
      49.5%-50.8%). In 2014, cardiovascular diseases accounted for more than 846 000
      deaths (95% UI, 827-865 thousand deaths) and 11.7 million years of life lost (95%
      UI, 11.6-11.9 million years of life lost). The gap in age-standardized
      cardiovascular disease mortality rates between counties at the 10th and 90th
      percentile declined 14.6% from 172.1 deaths per 100 000 persons in 1980 to 147.0
      deaths per 100 000 persons in 2014 (posterior probability of decline >99.9%). In
      2014, the ratio between counties at the 90th and 10th percentile was 2.0 for
      ischemic heart disease (119.1 vs 235.7 deaths per 100 000 persons) and 1.7 for
      cerebrovascular disease (40.3 vs 68.1 deaths per 100 000 persons). For other
      cardiovascular disease causes, the ratio ranged from 1.4 (aortic aneurysm: 3.5 vs
      5.1 deaths per 100 000 persons) to 4.2 (hypertensive heart disease: 4.3 vs 17.9
      deaths per 100 000 persons). The largest concentration of counties with high
      cardiovascular disease mortality extended from southeastern Oklahoma along the
      Mississippi River Valley to eastern Kentucky. Several cardiovascular disease
      conditions were clustered substantially outside the South, including atrial
      fibrillation (Northwest), aortic aneurysm (Midwest), and endocarditis (Mountain
      West and Alaska). The lowest cardiovascular mortality rates were found in the
      counties surrounding San Francisco, California, central Colorado, northern
      Nebraska, central Minnesota, northeastern Virginia, and southern Florida.
      Conclusions and Relevance: Substantial differences exist between county ischemic
      heart disease and stroke mortality rates. Smaller differences exist for diseases
      of the myocardium, atrial fibrillation, aortic and peripheral arterial disease,
      rheumatic heart disease, and endocarditis.

PMID- 28510679
TI  - Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and
      Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.
AB  - Importance: Synovitis is common and is associated with progression of structural
      characteristics of knee osteoarthritis. Intra-articular corticosteroids could
      reduce cartilage damage associated with synovitis but might have adverse effects
      on cartilage and periarticular bone. Objective: To determine the effects of intra
      articular injection of 40 mg of triamcinolone acetonide every 3 months on
      progression of cartilage loss and knee pain. Design, Setting, and Participants:
      Two-year, randomized, placebo-controlled, double-blind trial of intra-articular
      triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic
      features of synovitis in 140 patients. Mixed-effects regression models with a
      random intercept were used to analyze the longitudinal repeated outcome measures.
      Patients fulfilling the American College of Rheumatology criteria for symptomatic
      knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts
      Medical Center beginning February 11, 2013; all patients completed the study by
      January 1, 2015. Interventions: Intra-articular triamcinolone (n = 70) or saline
      (n = 70) every 12 weeks for 2 years. Main Outcomes and Measures: Annual knee
      magnetic resonance imaging for quantitative evaluation of cartilage volume
      (minimal clinically important difference not yet defined), and Western Ontario
      and McMaster Universities Osteoarthritis index collected every 3 months (Likert
      pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically
      important improvement, 3.94). Results: Among 140 randomized patients (mean age,
      58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular
      triamcinolone resulted in significantly greater cartilage volume loss than did
      saline for a mean change in index compartment cartilage thickness of -0.21 mm vs 
      0.10 mm (between-group difference, -0.11 mm; 95% CI, -0.20 to -0.03 mm); and no
      significant difference in pain (-1.2 vs -1.9; between-group difference, -0.6; 95%
      CI, -1.6 to 0.3). The saline group had 3 treatment-related adverse events
      compared with 5 in the triamcinolone group and had a small increase in hemoglobin
      A1c levels (between-group difference, -0.2%; 95% CI, -0.5% to -0.007%).
      Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis, 2
      years of intra-articular triamcinolone, compared with intra-articular saline,
      resulted in significantly greater cartilage volume loss and no significant
      difference in knee pain. These findings do not support this treatment for
      patients with symptomatic knee osteoarthritis. Trial Registration:
      ClinicalTrials.gov Identifier: NCT01230424.

PMID- 28510681
TI  - Reducing Risk of Dementia in Older Age.

PMID- 28510683
TI  - Determination.

PMID- 28510685
TI  - Scarcity of Safe Water a Looming Threat to Children.

PMID- 28510680
TI  - Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure
      With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized
      Clinical Trial.
AB  - Importance: Iron deficiency is present in approximately 50% of patients with
      heart failure with reduced left ventricular ejection fraction (HFrEF) and is an
      independent predictor of reduced functional capacity and mortality. However, the
      efficacy of inexpensive readily available oral iron supplementation in heart
      failure is unknown. Objective: To test whether therapy with oral iron improves
      peak exercise capacity in patients with HFrEF and iron deficiency. Design,
      Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized
      clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a
      serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299
      ng/mL with transferrin saturation of less than 20%. Participants were enrolled
      between September 2014 and November 2015 at 23 US sites. Interventions: Oral iron
      polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks.
      Main Outcomes and Measures: The primary end point was a change in peak oxygen
      uptake (Vo2) from baseline to 16 weeks. Secondary end points were change in 6
      minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT
      proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy
      Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life).
      Results: Among 225 randomized participants (median age, 63 years; 36% women) 203
      completed the study. The median baseline peak Vo2 was 1196 mL/min (interquartile
      range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887
      1449 mL/min) in the placebo group. The primary end point, change in peak Vo2 at
      16 weeks, did not significantly differ between the oral iron and placebo groups
      (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P =
      .46). Similarly, at 16 weeks, there were no significant differences between
      treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6
      m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, 
      2.4 to 4.4), all P > .05. Conclusions and Relevance: Among participants with
      HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity
      over 16 weeks. These results do not support use of oral iron supplementation in
      patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier:
      NCT02188784.

PMID- 28510687
TI  - Massive Polio Vaccination Drive in African Nations.

PMID- 28510686
TI  - Freeze-dried Rotavirus Vaccine Shows Promise.

PMID- 28510690
TI  - Trichosporonosis in Pediatric Patients With a Hematologic Disorder.
AB  - Background: Trichosporonosis is an emerging and often fatal opportunistic fungal
      infection in immunocompromised patients, particularly those with hematologic
      malignancy, but data in children are lacking. Methods: We report here 3 cases of
      invasive infection caused by Trichosporon asahii in pediatric patients with acute
      lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also
      conducted a literature review and identified 16 additional reports of pediatric
      patients with invasive T asahii infection and an underlying malignant or
      nonmalignant hematologic disorder. Results: Of the 19 cases of invasive T asahii
      infection, the most commonly reported underlying hematologic disorder was acute
      lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most
      of the patients (94%) had neutropenia, defined as an absolute neutrophil count of
      <500 cells/mm3. Antifungal prophylaxis information was available in 6 of the 19
      cases, and micafungin use was reported in 5 cases. Treatment regimens frequently
      included voriconazole monotherapy (47%) or the combination of an azole antifungal
      with amphotericin B (35%). The mortality rate was 58%. Conclusions: Recognizing
      that echinocandins, which are increasingly used for prophylaxis in patients with
      a hematologic malignancy, are not active against Trichosporon species is of
      critical importance. The recommended first-line therapy for trichosporonosis is
      voriconazole, but successful outcome depends largely on the underlying immune
      status of the host.

PMID- 28510689
TI  - Chronic Enteropathy Associated With SLCO2A1 Gene [CEAS]-Characterisation of an
      Enteric Disorder to be Considered in the Differential Diagnosis of Crohn's
      Disease.
AB  - Small intestinal ulcers include mucosal damage caused by drugs, particularly
      nonsteroidal anti-inflammatory drugs [NSAIDs], infectious diseases, and
      idiopathic inflammatory bowel disease. Previously, a group of Japanese
      investigators reported an unusual and uncommon type of enteritis and referred to
      the condition as chronic nonspecific multiple ulcers of the small intestine
      [CNSU]. CNSU is characterised by chronic blood and protein loss through
      persistent small intestinal ulcers. Recently, four candidate mutations in the
      solute carrier organic anion transporter family, member 2A1 [SLCO2A1] gene,
      encoding a prostaglandin transporter, were identified by whole-exome sequencing
      in patients with CNSU. However, because the name 'CNSU' was somewhat ambiguous,
      the more appropriate nomenclature of 'chronic enteropathy associated with the
      SLCO2A1 gene' [CEAS] has been suggested. CEAS ulcers are characterised by
      multiple, circular or eccentric oblique, shallow lesions with discrete margins.
      The most frequently affected site of CEAS is the ileum, in contrast to
      'cryptogenic multifocal ulcerous stenosing enteritis [CMUSE]', for which the most
      frequent site is the jejunum. Impaired prostaglandin utilisation is thought to
      cause the small intestinal mucosal damage observed in CEAS, CMUSE, and NSAID
      induced enteropathy. This review article focuses on endoscopic and clinical
      features of genetically diagnosed CEAS, accumulated in a nationwide survey, and
      illustrates the observations in the format of an atlas.

PMID- 28510692
TI  - Disseminated Neonatal Herpes Simplex Virus Type 1 After a Water Birth.
AB  - Neonatal herpes simplex virus (NHSV) infections are associated with significant
      morbidity and mortality. Numerous factors influence the transmission of HSV
      infection to newborns; however, immersion in water during labor has received very
      little attention as a possible risk factor despite the increasing popularity of
      water births. We report a case of disseminated NHSV type 1 infection, possibly
      acquired during a water birth. The purpose of this report is to alert healthcare
      providers to this potential route of transmission and to highlight the importance
      of screening guidelines for HSV before a water birth. Furthermore, it is
      essential to consider NHSV infection in any febrile infant who is not responding
      to standard empirical antibiotic management, even in the absence of herpetic
      lesions.

PMID- 28510691
TI  - NF-kappaB upregulation through epigenetic silencing of LDOC1 drives tumor biology
      and specific immunophenotype in Group A ependymoma.
AB  - Background: Inflammation has been identified as a hallmark of high-risk Group A
      (GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors
      drives an immune suppressive phenotype by polarizing infiltrating monocytes. This
      study determines the mechanism by which IL-6 is dysregulated in GpA EPN. Methods:
      Twenty pediatric GpA and 21 pediatric Group B (GpB) EPN had gene set enrichment
      analysis for MSigDB Hallmark gene sets performed. Protein and RNA from patients
      and cell lines were used to validate transcriptomic findings. GpA cell lines 811
      and 928 were used for in vitro experiments performed in this study. Results: The
      nuclear factor-kappaB (NF-kappaB) pathway is a master regulator of IL-6 and a
      signaling pathway enriched in GpA compared with GpB EPN. Knockdown of NF-kappaB
      led to significant downregulation of IL-6 in 811 and 928. NF-kappaB activation
      was independent of tumor necrosis factor alpha (TNF-alpha) stimulation in both
      cell lines, suggesting that NF-kappaB hyperactivation is mediated through an
      alternative mechanism. Leucine zipper downregulated in cancer 1 (LDOC1) is a
      known transcriptional repressor of NF-kappaB. In many cancers, LDOC1 promoter is
      methylated, which inhibits gene transcription. We found decreased LDOC1 gene
      expression in GpA compared with GpB EPN, and in other pediatric brain tumors. EPN
      cells treated with 5AZA-DC, demethylated LDOC1 regulatory regions, upregulated
      LDOC1 expression, and concomitantly decreased IL-6 secretion. Stable knockdown of
      LDOC1 in EPN cell lines resulted in a significant increase in gene transcription
      of v-rel avian reticuloendotheliosis viral oncogene homolog A, which correlated
      to an increase in NF-kappaB target genes. Conclusion: These results suggest that
      epigenetic silencing of LDOC1 in GpA EPN regulates tumor biology and drives
      inflammatory immune phenotype.

PMID- 28510694
TI  - Exploring the interrelationship between sport, health and social outcomes in the
      UK: implications for health policy.
AB  - Background: Policy agencies are now re-visiting early aspirations that sport, as
      a form of physical activity, can be an instrument to foster general health and
      also subjective well-being (SWB). Both of these concepts capture physical and
      mental health states. SWB also encompasses broader psychological and life
      satisfaction as well as mood and affect. Past and current policies also identify
      a link between sport, social capital and SWB. Methods: Structural Equation
      Modelling (SEM) is undertaken on data from the UK's Taking Part survey to
      investigate the interrelationships between sport, general health, social capital
      and SWB. Results: The SEM shows a simultaneous relationship between sport and
      SWB. The effect is mediated through general health. The results also show that
      there is no relationship between social capital and sport but a clear
      relationship between SWB and social capital. Conclusions: From a health policy
      perspective there should be an emphasis on encouraging greater sport
      participation, despite the difficulties that this poses, because there is a
      potential 'multiplier' effect on SWB and on general health through mediation. The
      multiplier effect occurs because once someone engages in sport and has their
      general health and SWB enhanced, then even further sport participation becomes
      likely, and subsequent general health and SWB, which would comprise both physical
      and mental health benefits. To target traditional non participants the research
      suggests that physical activity should be promoted for enjoyment, with health
      benefits subsequently following.

PMID- 28510693
TI  - Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis
      Infectiousness.
AB  - Background: Sputum from patients with tuberculosis contains subpopulations of
      metabolically active and inactive Mycobacterium tuberculosis with unknown
      implications for infectiousness. Methods: We assessed sputum microscopy with
      fluorescein diacetate (FDA, evaluating M. tuberculosis metabolic activity) for
      predicting infectiousness. Mycobacterium tuberculosis was quantified in
      pretreatment sputum of patients with pulmonary tuberculosis using FDA microscopy,
      culture, and acid-fast microscopy. These 35 patients' 209 household contacts were
      followed with prevalence surveys for tuberculosis disease for 6 years. Results:
      FDA microscopy was positive for a median of 119 (interquartile range [IQR], 47
      386) bacteria/uL sputum, which was 5.1% (IQR, 2.4%-11%) the concentration of acid
      fast microscopy-positive bacteria (2069 [IQR, 1358-3734] bacteria/MUL).
      Tuberculosis was diagnosed during follow-up in 6.4% (13/209) of contacts. For
      patients with lower than median concentration of FDA microscopy-positive M.
      tuberculosis, 10% of their contacts developed tuberculosis. This was
      significantly more than 2.7% of the contacts of patients with higher than median
      FDA microscopy results (crude hazard ratio [HR], 3.8; P = .03). This association
      maintained statistical significance after adjusting for disease severity,
      chemoprophylaxis, drug resistance, and social determinants (adjusted HR, 3.9; P =
      .02). Conclusions: Mycobacterium tuberculosis that was FDA microscopy negative
      was paradoxically associated with greater infectiousness. FDA microscopy-negative
      bacteria in these pretreatment samples may be a nonstaining, slowly metabolizing
      phenotype better adapted to airborne transmission.

PMID- 28510688
TI  - Two-component systems required for virulence in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a versatile opportunistic pathogen capable of infecting
      a broad range of hosts, in addition to thriving in a broad range of environmental
      conditions outside of hosts. With this versatility comes the need to tightly
      regulate its genome to optimise its gene expression and behaviour to the
      prevailing conditions. Two-component systems (TCSs) comprising sensor kinases and
      response regulators play a major role in this regulation. This minireview
      discusses the growing number of TCSs that have been implicated in the virulence
      of P. aeruginosa, with a special focus on the emerging theme of multikinase
      networks, which are networks comprising multiple sensor kinases working together,
      sensing and integrating multiple signals to decide upon the best response. The
      networks covered in depth regulate processes such as the switch between acute and
      chronic virulence (GacS network), the Cup fimbriae (Roc network and Rcs/Pvr
      network), the aminoarabinose modification of lipopolysaccharide (a network
      involving the PhoQP and PmrBA TCSs), twitching motility and virulence (a network
      formed from the Chp chemosensory pathway and the FimS/AlgR TCS), and biofilm
      formation (Wsp chemosensory pathway). In addition, we highlight the important
      interfaces between these systems and secondary messenger signals such as cAMP and
      c-di-GMP.

PMID- 28510695
TI  - Effects of an autoinducer analogue on antibiotic tolerance in Pseudomonas
      aeruginosa.
AB  - Objectives: Antibiotic tolerance causes chronic, refractory and persistent
      infections. In order to advance the development of a new type of drug for the
      treatment of infectious diseases, we herein investigated the effects of a newly
      synthesized analogue of the Pseudomonas aeruginosa quorum-sensing autoinducer
      named AIA-1 ( a uto i nducer a nalogue) on antibiotic tolerance in P. aeruginosa
      . Methods: A P. aeruginosa luminescent strain derived from PAO1 was injected into
      neutropenic ICR mice and bioluminescence images were acquired for a period of
      time after treatments with antibiotics and AIA-1. In vitro susceptibility testing
      and killing assays for the planktonic and biofilm cells of PAO1 were performed
      using antibiotics and AIA-1. The expression of quorum-sensing-related genes was
      examined using real-time PCR. Results: In vivo and in vitro assays showed that
      AIA-1 alone did not exert any bactericidal effects and also did not affect the
      MICs of antibiotics. However, the combined use of AIA-1 and antibiotics exerted
      markedly stronger therapeutic effects against experimental infection than
      antibiotics alone. The presence of AIA-1 also enhanced the killing effects of
      antibiotics in planktonic and biofilm cells. Although AIA-1 did not inhibit the
      expression of lasB and rhlA genes, which are directly regulated by quorum
      sensing, it clearly suppressed expression of the rpoS gene. Conclusions: The new
      compound, AIA-1, did not alter the antibiotic susceptibility of P. aeruginosa by
      itself; however, its addition enhanced the antibacterial activity of antibiotics.
      AIA-1 did not inhibit quorum sensing, but reduced the antibiotic tolerance of P.
      aeruginosa by suppressing rpoS gene expression.

PMID- 28510696
TI  - Autologous Adipose-Derived Tissue Matrix Part II: Implantation Biology.
AB  - Background: In part 1 of this study it was shown that liposuctioned fat could be
      a sufficient source of autologous collagen for use as a filler or in
      reconstruction. The collagen composition in liposuctioned fat was shown to form a
      cross-linked helical matrix composed of types II, III, and IV. Additionally,
      viable adipocytes and fibroblasts among other cells were found. Objectives: The
      purpose of this research was to study the biology of this matrix after subsequent
      implantation compared to Juvederm (Allergan, Parsippany, NJ) common soft tissue
      filler. Methods: Fat was obtained from individuals undergoing routine liposuction
      and was processed by a two-step process to obtain a connective tissue matrix. The
      matrix was then cryo-frozen for a minimum of 4 weeks after which it was thawed
      and implanted in 46 nude mice. Juvederm Ultra was used as the control article and
      the animals followed for one year. Results: Liposuctioned fat was obtained from
      10 individuals and processed as previously described. Mice were harvested at 3,
      6, 9, and 12 months and histology obtained. There were no adverse effects from
      either article and the bio-reactivity rating was 0. The implanted collagen
      compared favorably to Juvederm at all stages and was found to be replaced by new
      collagen and fat. Conclusions: A collagen matrix with viable cells for autologous
      use can be obtained from liposuctioned fat which has been processed and cryo
      frozen. The material lasts at least one year and is slowly replaced by new
      collagenand fat. Level of Evidence: 5.

PMID- 28510698
TI  - XSuLT: a web server for structural annotation and representation of sequence
      structure alignments.
AB  - The web server XSuLT, an enhanced version of the protein alignment annotation
      program JoY, formats a submitted multiple-sequence alignment using three
      dimensional (3D) structural information in order to assist in the comparative
      analysis of protein evolution and in the optimization of alignments for
      comparative modelling and construct design. In addition to the features analysed
      by JoY, which include secondary structure, solvent accessibility and sidechain
      hydrogen bonds, XSuLT annotates each amino acid residue with residue depth, chain
      and ligand interactions, inter-residue contacts, sequence entropy, root mean
      square deviation and secondary structure and disorder prediction. It is also now
      integrated with built-in 3D visualization which interacts with the formatted
      alignment to facilitate inspection and understanding. Results can be downloaded
      as stand-alone HTML for the formatted alignment and as XML with the underlying
      annotation data. XSuLT is freely available at
      http://structure.bioc.cam.ac.uk/xsult/.

PMID- 28510699
TI  - Invasive Pneumococcal Disease in Infants Aged 0-60 Days in the United States in
      the 13-Valent Pneumococcal Conjugate Vaccine Era.
AB  - We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD)
      at 8 children's hospitals in the United States (2005-2015). After the
      introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by
      PCV13 serotypes decreased ~30% providing some evidence of indirect protection.
      However, approximately 60% of IPD was still caused by PCV13 serotypes.

PMID- 28510701
TI  - Sputum Microscopy and Mycobacterium tuberculosis Infectiousness.

PMID- 28510697
TI  - BCCIPbeta modulates the ribosomal and extraribosomal function of S7 through a
      direct interaction.
AB  - Extraribosomal functions of ribosomal proteins (RPs) have gained much attention
      for their implications in tumorigenesis and progression. However, the regulations
      for transition between the ribosomal and extraribosomal functions of RPs are
      rarely reported. Herein, we identified a ribosomal protein S7-interacting
      partner, BCCIPbeta, which modulates the functional conversion of S7. Through the
      N-terminal acidic domain, BCCIPbeta interacts with the central basic region in S7
      and regulates the extraribosomal distribution of S7. BCCIPbeta deficiency
      abrogates the ribosomal accumulation but enhances the ribosome-free location of
      S7. This translocation further impairs protein synthesis and triggers ribosomal
      stress. Consequently, BCCIPbeta deficiency suppresses the ribosomal function and
      initiates the extraribosomal function of S7, resulting in restriction of cell
      proliferation. Moreover, clinically relevant S7 mutations were found to dampen
      the interaction with BCCIPbeta and facilitate the functional transition of S7. In
      conclusion, BCCIPbeta, as a S7 modulator, contributes to the regulation of
      ribosomal and extraribosomal functions of S7 and has implications in cell growth
      and tumor development.

PMID- 28510700
TI  - Enhanced biological activities of gamma-irradiated persimmon leaf extract.
AB  - The aim of this study was to compare the anti-oxidative and anti-inflammatory
      activities of gamma-irradiated persimmon leaf extract (GPLE) with those of non
      irradiated persimmon leaf extract (PLE). Ethanolic extract of persimmon leaf was
      exposed to gamma irradiation at a dose of 10 kGy. After gamma irradiation, the
      color of the extract changed from dark brown to light brown. The anti-oxidative
      and anti-inflammatory activities of GPLE and PLE were assessed from: total
      polyphenol and total flavonoid contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      assay; 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and
      levels of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2
      (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). The
      total polyphenol contents of GPLE and PLE were determined to be 224.44 +/- 1.54
      and 197.33 +/- 5.81 mg gallic acid equivalents (GAE)/g, respectively, and the
      total flavonoid contents of GPLE and PLE were 206.27 +/- 1.15 and 167.60 +/- 2.00
      mg quercetin equivalents (QUE)/g, respectively. The anti-oxidant activities of
      GPLE and PLE as measured by DPPH assays were 338.33 +/- 30.19 MUg/ml (IC50) and
      388.68 +/- 8.45 MUg/ml (IC50), respectively, and those measured by ABTS assays
      were 510.49 +/- 15.12 MUg/ml (IC50) and 731.30 +/- 10.63 MUg/ml (IC50),
      respectively. IC50 is the inhibitor concentration that reduces the response by
      50%. GPLE strongly inhibited the production of NO, PGE2 and IL-6 compared with
      PLE in lipopolysaccharide-stimulated RAW264.7 macrophages. Furthermore, GPLE
      significantly inhibited the production of TNF-alpha and IL-6 cytokines compared
      with PLE in phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated HMC-1
      human mast cells. These results indicate that gamma irradiation of PLE can
      enhance its anti-oxidative and anti-inflammatory activities through elevation of
      the phenolic contents. Therefore, gamma-irradiated PLE has potential for use in
      the food and cosmetic industries.

PMID- 28510702
TI  - Linking Vegetation Structure and Spider Diversity in Riparian and Adjacent
      Habitats in Two Rivers of Central Argentina: An Analysis at Two Conceptual
      Levels.
AB  - The link between vegetation structure and spider diversity has been well explored
      in the literature. However, few studies have compared spider diversity and its
      response to vegetation at two conceptual levels: assemblage (species diversity)
      and ensemble (guild diversity). Because of this, we studied spider diversity in
      riparian and adjacent habitats of a river system from the Chacoan subregion in
      central Argentina and evaluated their linkage with vegetation structure at these
      two levels. To assess vegetation structure, we measured plant species richness
      and vegetation cover in the herb and shrub - tree layers. We collected spiders
      for over 6 months by using vacuum netting, sweep netting and pitfall traps. We
      collected 3,808 spiders belonging to 119 morphospecies, 24 families and 9 guilds.
      At spider assemblage level, SIMPROF analysis showed significant differences among
      studied habitats. At spider ensemble level, nevertheless, we found no significant
      differences among habitats. Concerning the linkage with vegetation structure,
      BIOENV test showed that spider diversity at either assemblage or ensemble level
      was not significantly correlated with the vegetation variables assessed. Our
      results indicated that spider diversity was not affected by vegetation structure.
      Hence, even though we found a pattern in spider assemblages among habitats, this
      could not be attributed to vegetation structure. In this study, we show that
      analyzing a community at two conceptual levels will be useful for recognizing
      different responses of spider communities to vegetation structure in diverse
      habitat types.

PMID- 28510704
TI  - Skin Disorders in Egyptian Children with beta-Thalassemia Major.
AB  - Background: Thalassemia major is one of the common genetic disorders in Egypt.
      Skin disorders are usually neglected and frequently underdiagnosed among these
      patients. Objective: This work aimed to study the frequency and pattern of skin
      manifestations in Egyptian children with beta-thalassemia. Methods: Fifty-four
      beta-thalassemia major patients being followed at the Hematology Clinic of Beni
      Suef University Hospital were selected to participate in this study. All patients
      underwent detailed history evaluation, clinical examination and laboratory
      investigations, including complete blood count and serum ferritin. All patients
      were examined by a dermatologist to record any skin disorders. Results: Pruritus
      (37%), scars (33.3%), hyperpigmentation (31.5%) and xerosis (22.2%) were the most
      common findings. We found significant relations between serum ferritin and the
      occurrence of scars, hyperpigmentation, xerosis and ephelides (p <0.05). Also,
      significant associations between use of deferoxamine and scars (p=0.004),
      hyperpigmentation (p=0.004), xerosis (p=0.03) and ephelides (p=0.042) were found.
      Conclusion: Skin disorders are frequent in Egyptian children with thalassemia
      major. Careful skin examination is required to provide early diagnosis.

PMID- 28510703
TI  - Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male
      fertility: a study using adipose triglyceride lipase deficient mice.
AB  - STUDY QUESTION: Does the deletion of adipose triglyceride lipase (Atgl) gene
      impair male fertility? SUMMARY ANSWER: The deletion of Atgl gene impaired male
      fertility but the effect was partially reversed by a low long-chain triglyceride
      (TG) diet. WHAT IS KNOWN ALREADY: ATGL specifically hydrolyses long-chain fatty
      acid TG to diacylglycerol and a high level of expression of ATGL in testes has
      been reported. However, the role of ATGL in male fertility is unknown. STUDY
      DESIGN, SIZE, DURATION: To investigate the effect of deletion of Atgl gene on
      male fertility, cauda epididymides and testes were collected from wild-type,
      heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal
      sperm analysis and histological analysis of the testes were performed. To
      investigate whether a medium-chain triglycerides (MCTs) replacement diet
      mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl
      deficient mice were fed a MCT replacement diet, or a standard diet including long
      chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n
      = 22). The systematic and local effects of the MCT replacement diet on
      spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks
      of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Hematoxylin and eosin staining
      in paraffin-embedded sections of testes and Oil Red O staining in frozen sections
      of testes were performed. The epididymal sperm concentrations were analyzed.
      Statistical analyses were performed using the Student's t-test or Mann-Whitney U
      test with Shapiro-Wilk Normality test. MAIN RESULTS AND THE ROLE OF CHANCE:
      Although heterozygous mice were fertile and showed a similar number of epididymal
      total and motile sperm concentrations to wild-type mice, the deletion of Atgl
      gene in homozygous mice led to accumulation of TG deposits in testes and impaired
      spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation
      process required for sperm to acquire the ability to move forward in the
      epididymis. The MCT replacement diet for 6 weeks increased the plasma level of
      non-esterified fatty acid (NEFA) (1.5-fold, P = 0.005), but not the plasma total
      cholesterol (T-Cho) and TG levels. In testes, the MCT replacement diet decreased
      the number of Oil Red O stain positive vacuoles (-40%, P < 0.001) and increased
      testis tissue weight (1.1-fold, P = 0.012), total sperm concentration (1.5-fold,
      P = 0.011) and motile sperm concentration (2.1-fold, P < 0.001) compared to the
      control group. However, there was no significant change in the sperm survival
      rate between the two groups. LARGE SCALE DATA: None. LIMITATIONS REASONS FOR
      CAUTION: One previous study reported that Atgl-deficient male mice were fertile.
      In most studies heterozygous Atgl(+/-) mice were used to generate homozygous Atgl
      deficient Atgl(-/-) mice. Although the same gene targeting mice were used in this
      study and the formation of vaginal plugs were observed after mating with Atgl(-/
      ) male mice, there were no pregnant wild-type mice observed after mating with
      Atgl(-/-) male mice. WIDER IMPLICATIONS OF THE FINDINGS: Local TG metabolism in
      the male reproductive system could affect spermatogenesis and sperm motility in
      men. The MCT replacement diet could be an effective therapy for idiopathic non
      obstructive oligozoospermia or asthenozoospermia in men with low levels of serum
      NEFA. STUDY FUNDING AND COMPETING INTEREST(S): This study was supported in part
      by the Japan Society for the Promotion of Science JSPS KAKENHI Grant (Nos.
      JP24249080, JP25462557, JP16K11086). The authors declare no conflict of interest.

PMID- 28510705
TI  - Crystal structure of octocoral lectin SLL-2 complexed with Forssman antigen
      tetrasaccharide.
AB  - A symbiosis-related lectin, SLL-2, from the octocoral Sinularia lochmodes,
      distributes densely on the cell surface of microalgae, Symbiodinium sp., an
      endosymbiotic dinoflagellate of the coral, and is also shown to be a chemical cue
      that transforms dinoflagellates into a non-motile (coccoid) symbiotic state. SLL
      2 binds to the sugar chain of the molecule similar to Forssman antigen
      pentasaccharide (GalNAcalpha1-3GalNAcbeta1-3 Galalpha1-4 Galbeta1-4Glc) on the
      surface of microalgae with high affinity. Here we report the crystal structure of
      the complex between SLL-2 and Forssman antigen tetrasaccharide (GalNAcalpha1
      3GalNAcbeta1-3 Galalpha1-4 Galbeta) at 3.4 A resolution. In an asymmetric unit of
      the crystal, there are two hexameric molecules with totally twelve sugar
      recognition sites. At the nine in twelve sites, the first and second saccharides
      of the Forssman antigen tetrasaccharide bind directly to galactopyranoside
      binding site of SLL-2, whereas the third and fourth saccharides have no
      interaction with the SLL-2 hexameric molecule that binds the first saccharide.
      The sugar chain bends at alpha-1,4-glycosidic linkage between the third and
      fourth saccharides toward the position that we defined as a pyranoside binding
      site in the crystal structure of the complex between SLL-2 and GalNAc. The
      structure allowed us to suggest a possible binding mode of the Forssman antigen
      pentasaccharide to SLL-2. These observations support our hypothesis that the
      binding of SLL-2 to the cell surface sugars of zooxanthella in a unique manner
      might trigger some physiological changes of the cell to adapt symbiosis with the
      host coral.

PMID- 28510707
TI  - Policing Intimate Partner Violence: Attitudes toward Risk Assessment and
      Collaboration with Social Workers.
AB  - Risk-informed collaborative police-social service interventions are an emerging
      strategy intended to enhance offender accountability and victim-survivors' safety
      in intimate partner violence (IPV) cases. These interventions use risk assessment
      to determine appropriate interventions and enhance the police response for
      dangerous offenders by engaging in collaboration with social work advocates.
      Because little is known about the responsiveness of police officers to risk
      informed collaborative interventions, this study examines police officer (N =
      544) attitudes toward IPV risk assessment and collaboration with social workers.
      The majority of police officers did not believe a social worker would be helpful
      at the scene of an IPV incident. However, those who agreed that a social worker
      would be helpful were more likely to be knowledgeable about the dynamics of IPV.
      Officers who believed risk assessment was important were more likely to believe
      that the police response to IPV is necessary. Finally, officers' perceived
      knowledge about risk for homicide was not consistently associated with actual
      knowledge about IPV. These findings suggest a need for knowledgeable social
      workers to collaborate with police, particularly in high-risk cases, and to offer
      training for officers on risk factors for homicide, coercive control, and
      misperceptions about IPV.

PMID- 28510709
TI  - Clopidogrel instead of prasugrel or ticagrelor after 1 month in stabilized ACS
      patients: back to square one for DAPT?

PMID- 28510706
TI  - Two Imported Cases of Congenital Rubella Syndrome and Infection-Control
      Challenges in New York State, 2013-2015.
AB  - Rubella was declared eliminated in the United States in 2004. During 2013-2015, 2
      infants with congenital rubella syndrome (CRS) were born in New York State. Both
      mothers were foreign born and traveled to Yemen during their pregnancy. Delayed
      consideration of CRS led to preventable exposures and a substantial public health
      response.

PMID- 28510708
TI  - Aberrant White Matter Microstructure in Children and Adolescents With the Subtype
      of Prader-Willi Syndrome at High Risk for Psychosis.
AB  - Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder caused by loss of
      the paternal 15q11.2-q13 locus, due to deletion (DEL), maternal uniparental
      disomy (mUPD), or imprinting center defects. Individuals with mUPD have up to 60%
      risk of developing psychosis in early adulthood. Given the increasing evidence
      for white matter abnormalities in psychotic disorders, we investigated white
      matter microstructure in children and adolescents with PWS, with a particular
      emphasis on the DEL and mUPD subtypes. Magnetic resonance diffusion weighted
      images were acquired in 35 directions at 3T and analyzed using fractional
      anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values obtained
      by tract-based spatial statistics (TBSS) in 28 children and adolescents with PWS
      and 61 controls. In addition, we employed a recently developed white matter
      pothole approach, which does not require local FA differences to be spatially co
      localized across subjects. After accounting for age and gender, individuals with
      PWS had significantly lower global FA and higher MD, compared with controls.
      Individuals with mUPD had lower FA in multiple regions including the corpus
      callosum, cingulate, and superior longitudinal fasciculus and larger potholes,
      compared with DEL and controls. The observed differences in individuals with mUPD
      are similar to the white matter abnormalities in individuals with psychotic
      disorders. Conversely, the subtle white matter abnormalities in individuals with
      DEL are consistent with their substantially lower risk of psychosis. Future
      studies to investigate the specific neurobiological mechanism underlying the
      differential psychosis risk between the DEL and mUPD subtypes of PWS are highly
      warranted.

PMID- 28510710
TI  - Relationship Between Objectively Measured Physical Activity, Cardiovascular
      Disease Biomarkers, and Hearing Sensitivity Using Data From the National Health
      and Nutrition Examination Survey 2003-2006.
AB  - Purpose: Limited research has examined the interrelationships among
      cardiometabolic parameters, physical activity, and hearing function, which was
      this study's purpose. Method: Data from the National Health and Nutrition
      Examination Survey (NHANES) 2003-2006 were used in the path analyses. Physical
      activity and hearing function were both objectively measured. Various
      cardiometabolic parameters were assessed from a blood sample. Adults 30-85 years
      (N = 1,070) constituted the analytic sample. Results: Physical activity was
      negatively associated with triglycerides (beta = -0.11, p < .05) and insulin
      (beta = -0.27, p < .05); triglycerides (beta = 0.01, p < .05), and insulin (beta
      = 0.05, p < .05) were positively associated with high-frequency pure-tone average
      (HPTA). The direct path from physical activity to HPTA was nonsignificant (beta =
      0.01, p = .99). Conclusion: Physical activity was associated with select
      cardiovascular disease risk factors. Several cardiovascular disease risk factors
      were associated with hearing function.

PMID- 28510711
TI  - Obesity and Metabolic Unhealthiness Have Different Effects on Colorectal
      Neoplasms.
AB  - Context: Obesity and insulin resistance are risk factors for colorectal neoplasms
      (CRN), but data regarding metabolic status, obesity, and CRN are lacking.
      Objective: To investigate the relationship between metabolic status, obesity, and
      CRN in Koreans who underwent colonoscopy. Design: Retrospective, cross-sectional.
      Participants: Subjects were divided based on metabolic and obesity criteria, as
      follows: metabolically healthy nonobese (MHNO), metabolically healthy obese
      (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese
      (MUO). Main Outcome Measures: Multiple regression was used to identify CRN and
      advanced CRN risk factors, with the MHNO group as reference. Results: A total of
      10,235 subjects was included, as follows: 5096 MHNO, 1538 MHO, 1746 MUNO, and
      1855 MUO. Of these, 3297 had CRN (32.2%), and 434 (4.2%) had advanced CRN. Number
      of subjects with CRN in each group were: MHNO 25.8%, MHO 33.9%, MUNO 38.9%, and
      MUO 42.0% (P for trend < 0.001). Risk of CRN was increased in the MHO [odds ratio
      (OR) 1.239, 95% confidence interval (CI) 1.082 to 1.418, P = 0.002], the MUNO (OR
      1.233, 95% CI 1.086 to 1.400, P = 0.001), and the MUO groups (OR 1.510, 95% CI
      1.338 to 1.706, P < 0.001), whereas risk of advanced CRN was increased in the
      MUNO (OR 1.587, 95% CI 1.222 to 2.062, P = 0.001) and the MUO groups (OR 1.456,
      95% CI 1.116 to 1.900, P = 0.006). Conclusions: Obesity increased CRN risk with
      metabolically unhealthy status adding risk. For advanced CRN, metabolically
      unhealthy status increased the risk but obesity did not.

PMID- 28510712
TI  - Gender issues in arrhythmias: from atrial fibrillation to CRT and arrhythmogenic
      ventricular cardiomyopathy.

PMID- 28510713
TI  - RE: "DISASTERS: INTRODUCTION AND STATE OF THE ART".

PMID- 28510714
TI  - RE: "WHAT DO WE KNOW ABOUT THE ASSOCIATION BETWEEN FIREARM LEGISLATION AND
      FIREARM-RELATED INJURIES?"

PMID- 28510715
TI  - Quantitative specificity of STAT1 and several variants.
AB  - The quantitative specificity of the STAT1 transcription factor was determined by
      measuring the relative affinity to hundreds of variants of the consensus binding
      site including variations in the length of the site. The known consensus sequence
      is observed to have the highest affinity, with all variants decreasing binding
      affinity considerably. There is very little loss of binding affinity when the CpG
      within the consensus binding site is methylated. Additionally, the specificity of
      mutant proteins, with variants of amino acids that interact with the DNA, was
      determined and nearly all of them are observed to lose specificity across the
      entire binding site. The change of Asn at position 460 to His, which corresponds
      to the natural amino acid at the homologous position in STAT6, does not change
      the specificity nor does it change the length preference to match that of STAT6.
      These results provide the first quantitative analysis of changes in binding
      affinity for the STAT1 protein, and several variants of it, to hundreds of
      different binding sites including different spacer lengths, and the effect of CpG
      methylation.

PMID- 28510717
TI  - Fast Population Growth in Physogastry Reproduction of Luciaphorus perniciosus
      (Acari: Pygmephoridae) at Different Temperatures.
AB  - Luciaphorus perniciosus Rack is one of the most serious pests of several
      cultivated mushroom species including Ganoderma lucidum (Fr.), Flammulina
      velutipes Karst., Auricularia polytricha (Mont.) Saac., Lentinus polychrous Lev.,
      and Lentinus squarrosulus (Mont.) Singer in Thailand. Adult female Lu.
      perniciosus produce offspring inside their physogastric hysterosomas, with all
      embryos developing through to the adult stage while remaining in the abdomen.
      Once the abdomen ruptures, the female parent dies and the offspring consisting of
      mostly fertilized female adults along with a few male adults continue to emerge
      from the cadaver of the mother for a period of several days. This peculiar type
      of reproduction after the death of the mother is a special case for life table
      analysis and has not been discussed previously in demographic analyses. In this
      study, the life table data of this mite fed on Le. squarrosulus were collected at
      25, 30, and 35  degrees C and analyzed by using the age-stage, two-sex life
      table. The standard errors of population parameters were estimated by using the
      bootstrap technique (200,000 bootstraps). At 25, 30, and 35  degrees C, females
      started reproduction at ages 9, 5, and 3 d, respectively; the net reproductive
      rates (R0) were 192.27, 253.81, and 234.11 offspring. Due to their rapid
      development and high fecundity, the r values were as high as 0.4189, 0.8653, and
      1.0892 d-1 at 25, 30, and 35  degrees C, respectively. Computer projection
      indicated that the mushroom mites Lu. perniciosus is capable of a threefold daily
      increase at 35  degrees C.

PMID- 28510716
TI  - Phosphorylation of the transcriptional repressor MYB15 by mitogen-activated
      protein kinase 6 is required for freezing tolerance in Arabidopsis.
AB  - The expression of CBF (C-repeat-binding factor) genes is required for freezing
      tolerance in Arabidopsis thaliana. CBFs are positively regulated by INDUCER OF
      CBF EXPRESSION1 (ICE1) and negatively regulated by MYB15. These transcription
      factors directly interact with specific elements in the CBF promoters. Mitogen
      activated protein kinase (MAPK/MPK) cascades function upstream to regulate CBFs.
      However, the mechanism by which MPKs control CBF expression during cold stress
      signaling remains unknown. This study showed that the activity of MYB15, a
      transcriptional repressor of cold signaling, is regulated by MPK6-mediated
      phosphorylation. MYB15 specifically interacts with MPK6, and MPK6 phosphorylates
      MYB15 on Ser168. MPK6-induced phosphorylation reduced the affinity of MYB15
      binding to the CBF3 promoter and mutation of its phosphorylation site
      (MYB15S168A) enhanced the transcriptional repression of CBF3 by MYB15.
      Furthermore, transgenic plants overexpressing MYB15S168A showed significantly
      reduced CBF transcript levels in response to cold stress, compared with plants
      overexpressing MYB15. The MYB15S168A-overexpressing plants were also more
      sensitive to freezing than MYB15-overexpressing plants. These results suggest
      that MPK6-mediated regulation of MYB15 plays an important role in cold stress
      signaling in Arabidopsis.

PMID- 28510719
TI  - Featured Article: Trajectories of Glycemic Control Over Adolescence and Emerging
      Adulthood: An 11-Year Longitudinal Study of Youth With Type 1 Diabetes.
AB  - Objective: To identify trajectories of glycemic control over adolescence and
      emerging adulthood and to test whether demographic and psychosocial variables
      distinguished these trajectories. Methods: We enrolled 132 youth with type 1
      diabetes when they were average age 12 and followed them for 11 years. We used
      group-based trajectory modeling to identify distinct patterns of glycemic
      control, and examined whether age 12 demographic and psychosocial variables
      distinguished the subsequent trajectories. Results: We identified 5 trajectories
      of glycemic control: stable on target, stable above target, volatile late peak,
      stable high, and inverted U. Parent social status and household structure
      distinguished the more problematic trajectories from the stable on target group.
      Friend conflict, psychological distress, unmitigated communion, and self-care
      behavior at age 12 distinguished problematic glycemic control trajectories from
      the stable on target group. Conclusions: These results can be used to identify
      youth who are at risk for deteriorating glycemic control over adolescence.

PMID- 28510718
TI  - Multimodality Imaging in Restrictive Cardiomyopathies: An EACVI expert consensus
      document In collaboration with the "Working Group on myocardial and pericardial
      diseases" of the European Society of Cardiology Endorsed by The Indian Academy of
      Echocardiography.
AB  - Restrictive cardiomyopathies (RCMs) are a diverse group of myocardial diseases
      with a wide range of aetiologies, including familial, genetic and acquired
      diseases and ranging from very rare to relatively frequent cardiac disorders. In
      all these diseases, imaging techniques play a central role. Advanced imaging
      techniques provide important novel data on the diagnostic and prognostic
      assessment of RCMs. This EACVI consensus document provides comprehensive
      information for the appropriateness of all non-invasive imaging techniques for
      the diagnosis, prognostic evaluation, and management of patients with RCM.

PMID- 28510720
TI  - Effects of a 3D segmental prosthetic system for tricuspid valve annulus
      remodelling on the right coronary artery: a human cadaveric coronary angiography
      study.
AB  - OBJECTIVES: A prosthetic system to repair secondary tricuspid valve regurgitation
      was developed. The conceptual engineering of the current device is based on 3D
      segmental remodelling of the tricuspid valve annulus in lieu of reductive
      annuloplasty. This study was designed to investigate the operational safety of
      the current prosthetic system with regard to the anatomical integrity of the
      right coronary artery (RCA) in fresh cadaveric human hearts. METHODS: During the
      study period, from January to April 2016, the current prosthetic system was
      implanted on the tricuspid valve annulus in fresh cadaveric human hearts that met
      the study's inclusion criteria. The prepared specimens were investigated via
      selective coronary angiography of the RCA in the catheterization laboratory. The
      RCA angiographic anatomies were categorized as normal, distorted, kinked or
      occluded. RESULTS: Sixteen specimens underwent implantation of the current
      prosthetic system. The mean age of the cadaveric human hearts was 43.24 +/- 15.79
      years, with vehicle accident being the primary cause of death (59%). A dominant
      RCA was noticed in 62.5% of the specimens. None of the specimens displayed any
      injury, distortion, kinking or occlusion in the RCA due to the implantation of
      the prostheses. CONCLUSIONS: In light of the results of the present study,
      undertaken on fresh cadaveric human heart specimens, the current segmental
      prosthetic system for 3D remodelling of the tricuspid valve annulus seems to be
      safe vis-a-vis the anatomical integrity of the RCA. Further in vivo studies are
      needed to investigate the functional features of the current prosthetic system
      with a view to addressing the complex pathophysiology of secondary tricuspid
      valve regurgitation.

PMID- 28510722
TI  - Clinical Markers and Outcomes of Neonates With Herpes Simplex Virus
      Deoxyribonucleic Acid Persistence in Cerebrospinal Fluid in Disseminated and
      Central Nervous System Infection.
AB  - We compared the clinical course of neonates with persistence of herpes simplex
      virus (HSV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) after 21
      days of treatment with high-dose acyclovir to that of neonates with clearance of
      the CSF after 21 days of therapy. Neonates with persistence of HSV DNA had a more
      severe clinical course with worse neurodevelopmental outcomes.

PMID- 28510721
TI  - Cold Tolerance of Pityophthorus juglandis (Coleoptera: Scolytidae) From Northern
      California.
AB  - Winter survivorship of insects is determined by a combination of physiological,
      behavioral, and microhabitat characteristics. We characterized the cold tolerance
      of the walnut twig beetle, Pityophthorus juglandis Blackman, a domestic alien
      invasive bark beetle that vectors a phytopathogenic fungus. The beetle and fungus
      cause thousand cankers disease in species of Juglans and Pterocarya. The disease
      is spreading in the United States of America (USA) and Italy. Contact
      thermocouple thermometry was used to measure the supercooling points of adults
      and larvae and lower lethal temperatures of adults from a population from
      northern California. Supercooling points ranged from -12.2  degrees C to - 25.0 
      degrees C for adults and -13.6  degrees C to - 23.5  degrees C for larvae; lower
      lethal temperatures of adults ranged from -14  degrees C to - 23  degrees C. We
      found seasonal changes in adult supercooling points in fall, winter, and spring.
      The supercooling point for males was 0.5  degrees C colder than for females over
      all months and 1  degrees C colder in the winter than in other seasons. The cold
      tolerance strategy shifted in P. juglandis adults from freeze intolerance
      (December 2013 and January 2014) to partial freeze tolerance (February 2014). An
      intermediate level of cold tolerance with a plastic response to cold partially
      explains survival of P. juglandis outside of its native range in the southwestern
      USA. In addition, we characterized the relationship between minimum air
      temperatures and minimum phloem temperatures in two Juglans spp. in northern
      California and Colorado and characterized portions of the native geographic range
      of eastern black walnut, J. nigra L., that may be too cold currently for this
      insect to persist.

PMID- 28510723
TI  - Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in
      Patients Recently Treated with Azithromycin.
AB  - Background: Increasing azithromycin usage and resistance in Neisseria gonorrhoeae
      threatens current dual treatment. Because antimicrobial exposure influences
      resistance, we analyzed the association between azithromycin exposure and
      decreased susceptibility of N. gonorrhoeae. Methods: We included N. gonorrhoeae
      isolates of patients who visited the Amsterdam STI Clinic between 1999 and 2013
      (t0), with another clinic visit in the previous 60 days (t-1). Exposure was
      defined as the prescription of azithromycin at t-1. Using multivariable linear
      regression, we assessed the association between exposure and azithromycin minimum
      inhibitory concentration (MIC). Whole genome sequencing (WGS) was performed to
      produce a phylogeny and identify multilocus sequence types (MLST), N. gonorrhoeae
      multiantigen sequence types (NG-MAST), and molecular markers of azithromycin
      resistance. Results: We included 323 isolates; 212 were unexposed to
      azithromycin, 14 were exposed <=30 days, and 97 were exposed between 31 and 60
      days before isolation. Mean azithromycin MIC was 0.28 mg/L (range, <0.016-24
      mg/L). Linear regression adjusted for age, ethnicity, infection site, and
      calendar year showed a significant association between azithromycin exposure <=30
      days and MIC (beta, 1.00; 95% confidence interval, 0.44-1.56; P = .002). WGS was
      performed on 31 isolates: 14 unexposed, 14 exposed to azithromycin <=30 days
      before isolation, and 3 t-1 isolates. Exposure to azithromycin was significantly
      associated with A39T or G45D mtrR mutations (P = .046) but not with MLST or NG
      MAST types. Conclusions: The results suggest that frequent azithromycin use in
      populations at high risk of contracting N. gonorrhoeae induces an increase in MIC
      and may result in resistance.

PMID- 28510724
TI  - Relationship between the magnetic resonance imaging appearance of adenomyosis and
      endometriosis phenotypes.
AB  - STUDY QUESTION: What is the relationship between endometriosis phenotypes
      superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep
      infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic
      resonance imaging (MRI)? SUMMARY ANSWER: Focal adenomyosis located in the outer
      myometrium (FAOM) was observed more frequently in women with endometriosis, and
      was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY: An
      association between endometriosis and adenomyosis has been reported previously,
      although data regarding the association between MRI appearance of adenomyosis and
      the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE,
      DURATION: This was an observational, cross-sectional study using data
      prospectively collected from non-pregnant patients who were between 18 and 42
      years of age, and who underwent surgery for symptomatic benign gynecological
      conditions between January 2011 and December 2014. For each patient, a
      standardized questionnaire was completed during a face-to-face interview
      conducted by the surgeon during the month preceding the surgery. Only women with
      preoperative standardized uterine MRIs were retained for this study.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed on 292 patients
      with signed consent and available preoperative MRIs. After a thorough surgical
      examination of the abdomino-pelvic cavity, 237 women with histologically proven
      endometriosis were allocated to the endometriosis group and 55 symptomatic women
      without evidence of endometriosis to the endometriosis free group. The existence
      of diffuse or FAOM was studied in both groups and according to surgical
      endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE:
      Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n =
      292). Based on MRI, the distribution of adenomyosis was as follows: isolated
      diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%),
      associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated
      and associated to FAOM) was observed in one-third of the patients regardless of
      whether they were endometriotic patients or endometriosis free women taken as
      controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among
      endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed
      to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8
      cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking
      contrast, there was a significant increase in the frequency of FAOM in
      endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3
      cases); P < 0.001). FAOM correlated with the endometriosis phenotypes,
      significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3%
      (110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION: There was a possible
      selection bias due to the specificity of the study design, as it only included
      surgical patients in a referral center that specializes in endometriosis surgery.
      Therefore, women referred to our center may have suffered from particularly
      severe forms of endometriosis. This could explain the high number of women with
      DIE (166/237-70%) in our study group. This referral bias for women with severe
      lesions may have amplified the difference in association of FAOM with the
      endometriosis-affected patients compared to women without endometriosis.
      Furthermore, according to inclusion criteria, women in the endometriosis free
      group were symptomatic women. This may introduce some bias as symptomatic women
      may be more prone to have associated adenomyosis that in turn could have been
      overrepresented in the endometriosis free group. Whether this selection could
      have introduced a bias in the relationship between endometriosis and adenomyosis
      remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the door to
      future epidemiological, clinical and mechanistic studies aimed at better
      characterizing diffuse and focal adenomyosis. Further studies are necessary to
      adequately determine if diffuse and focal adenomyosis are two separate entities
      that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S): No
      funding supported this study. The authors have no conflict of interest to
      declare.

PMID- 28510726
TI  - Conflict Strategies in the Parent-Adult Child Tie: Generation Differences and
      Implications for Well-Being.
AB  - Objectives: Irritations often arise in intergenerational ties. Middle-aged
      individuals report that their relationships with adult children are more
      important and more negative than ties with aging parents. However, it is unclear
      whether midlife individuals use different interpersonal conflict strategies with
      adult children compared to aging parents, and whether the strategies used have
      implications for psychological well-being. Method: This study examined middle
      aged individuals' reports of conflict strategies with their adult children and
      their aging parents and their own depressive symptoms. Participants were from the
      Family Exchanges Study; middle-aged adults (N = 365, ages 45 to 66 years)
      reported on the conflict strategies used with each of their adult children and
      their aging parents. Results: Models revealed that middle-aged individuals use
      more active strategies (e.g., discussing problems) with their adult children than
      their aging parents. In contrast, individuals used more passive strategies (e.g.,
      avoidance) with aging parents than adult children. Further, passive strategies
      used with adult children are associated with greater depressive symptoms.
      Discussion: Findings are consistent with the intraindividual stake hypothesis and
      imply that conflict strategies used with adult children may be more consequential
      for psychological well-being than those used with aging parents.

PMID- 28510725
TI  - IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes
      in Chinese Patients With H7N9/H1N1pdm09 Influenza.
AB  - Background: We examined associations between single-nucleotide polymorphisms
      (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in
      Chinese. Methods: A multicenter study was conducted on 275 adult cases of avian
      (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic
      respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4
      rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary
      outcome analyzed was death. Results: IFITM3 and TLR3 SNPs were in Hardy-Weinberg
      equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88)
      were comparable to 1000 Genomes Han Chinese data. We found over-representation of
      homozygous IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P =
      .04) genotypes among fatal cases. Recessive genetic models showed their
      significant independent associations with higher death risks (adjusted hazard
      ratio [aHR] 2.78, 95% confidence interval [CI] 1.29-6.02, and aHR 4.85, 95% CI
      1.11-21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64
      7.59 per risk genotype; aHR 9.99, 95% CI 1.27-78.59 with both). Results were
      consistent for each influenza subtype and other severity indicators. The CD55 TT
      genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions: Host
      genetic factors may influence clinical outcomes of avian and pandemic influenza
      infections. Such findings have important implications on disease burden and
      patient care in at-risk populations.

PMID- 28510727
TI  - Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing
      a neurological disease in mice.
AB  - Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the
      Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in
      the brain, MPI and MPc. These isoforms differ in their splice acceptor sites;
      human MPI is translated into a polyglutamine tract associated with
      spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop
      codon, resulting in a shorter cytoplasmic tail. To gain insight into the
      functional role of the AS in vivo and whether modulating the splice patterns at
      this locus can be a potential therapeutic strategy for SCA6, here we created
      knockin mice that exclusively express MPc by inserting the splice-site mutation.
      The resultant Cacna1aCtmKO/CtmKO mice developed non-progressive neurological
      phenotypes, featuring early-onset ataxia and absence seizure without significant
      alterations in the basic properties of the channel. Interactions of Cav2.1 with
      Cavbeta4 and Rimbp2 were significantly reduced while those with GABAB2 were
      enhanced in the cerebellum of Cacna1aCtmKO/CtmKO mice. Treatment with the GABAB
      antagonist CGP35348 partially rescued the motor impairments seen in
      Cacna1aCtmKO/CtmKO mice. These results suggest that the carboxyl-terminal domain
      of Cav2.1 is not essential for maintaining the basic properties of the channel in
      the cerebellar Purkinje neurons but is involved in multiple interactions of
      Cav2.1 with other proteins, and plays an essential role in preventing a complex
      neurological disease.

PMID- 28510729
TI  - Political Social Work.

PMID- 28510728
TI  - Spatial and Temporal Dynamics of Aphids (Hemiptera: Aphididae) in the Columbia
      Basin and Northeastern Oregon.
AB  - Aphid species, such as the potato aphid, Macrosiphum euphorbiae Thomas, and the
      green peach aphid, Myzus persicae Sulzer, are routinely considered the most
      important pests of potatoes. Potato aphid, green peach aphid, and more recently,
      other aphids such as the bird cherry-oat aphid Rhopalosiphum padi L. have been
      identified as vectors of multiple plant pathogenic viruses in potatoes. Since
      2006, an area-wide trapping network consisting of ~60 sites was developed through
      collaboration between researchers, extension faculty, and stakeholders, to
      monitor aphid populations in the Columbia Basin of Oregon (Umatilla and Morrow
      counties) and in northeastern Oregon (Union and Baker counties). Over a 9-yr
      period (2006 to 2014), aphid specimens were collected weekly using yellow bucket
      traps and specimens were then identified and counted to determine population
      levels during the growing season (May-September). Thus, aphid population data
      were compiled and subjected to spatial and temporal distribution analysis.
      Weather data, obtained from an established network of weather stations located in
      the monitoring areas, were used in a nonparametric multiplicative regression
      analysis to determine which abiotic variables may impact aphid populations.
      Weather conditions were characterized using confidence intervals (CIs)
      established based on weather data from 1999 to 2005 for each environmental
      variable. Aphid populations were found to have a heterogeneous distribution in
      most years; a few sites had high aphid populations while low numbers were
      observed at most sites; aphids were also found to correlate with several abiotic
      variables, namely, elevation, previous season temperature, and previous season
      dew point.

PMID- 28510730
TI  - Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of
      healthcare/ventilator-associated MRSA pneumonia: a case-control study.

PMID- 28510731
TI  - Letter: Retention of ATRX and DAXX Expression in Meningiomas.

PMID- 28510732
TI  - Efficacy of Bistrifluron Termite Bait on Coptotermes lacteus (Isoptera:
      Rhinotermitidae) in Southern Australia.
AB  - Bistrifluron, a benzoylphenyl urea compound, was evaluated for efficacy against
      Coptotermes lacteus (Froggatt), a mound-building species in southern Australia.
      Bistrifluron bait (tradename Xterm) was delivered as containerized pellets
      inserted into plastic in-ground feeding stations implanted in the sides of
      mounds. Termites actively tunneled in the gaps between pellets and removed bait
      from the canisters. Two separate trials were conducted, one commencing on 22
      September 2011 and the second commencing on 30 November 2011. In trial 1, all 13
      treated colonies (seven single and six double treatments) were eliminated within
      19 wk, while all five untreated colonies remained healthy. In trial 2, all four
      treated colonies were eliminated within 14 wk. In trial 1, bait consumed or
      removed in treated mounds averaged 105 g for single treatments and 147 g for dual
      treatments, and overall ranged from 7 to 309 g (70-3,090 mg bistrifluron). In
      trial 2, the four treated colonies removed an average of 85 g of bait. At the
      time mounds were dismantled, all showed signs of inattention: external cracking,
      delamination, and general external weathering. Mound repair and temperature
      profile data indicate that colony decline commenced much earlier than 19 wk and
      14 wk, respectively, for trials 1 and 2, from as early as 4 wk onward. The
      ability of colonies to repair mound damage was impaired as early as 4 wk in some
      colonies, and mean internal mound temperatures in treated mounds began declining
      from 8 wk onward and clearly diverged from mean temperatures of untreated mounds
      thereafter.

PMID- 28510733
TI  - RADON DOSIMETRY FOR WORKERS: ICRP'S APPROACH.
AB  - The International Commission on Radiological Protection (ICRP) has recently
      published two reports on radon exposure; Publication 115 on lung cancer risks
      from radon and radon progeny and Publication 126 on radiological protection
      against radon exposure. A specific graded approach for the control of radon in
      workplaces is recommended where a dose assessment is required in certain
      situations. In its forthcoming publication on Occupational Intakes of
      Radionuclides (OIR) document, Part 3, effective dose coefficients for radon and
      thoron will be provided. These will be calculated using ICRP reference biokinetic
      and dosimetric models. Sufficient information and dosimetric data will be given
      so that site-specific dose coefficients can be calculated based on measured
      aerosol parameter values. However, ICRP will recommend a single dose coefficient
      of 12 mSv per working level month (WLM) for inhaled radon progeny to be used in
      most circumstances. This chosen reference value was based on both dosimetry and
      epidemiological data. In this paper, the application and use of dose coefficients
      for workplaces are discussed including the reasons for the choice of the
      reference value. Preliminary results of dose calculations for indoor workplaces
      and mines are presented. The paper also briefly describes the general approach
      for the management of radon exposure in workplaces based both on ICRP
      recommendations and the European directive (2013/59/EURATOM).

PMID- 28510735
TI  - Spinal Cord Compression Related to Spinal Cord Stimulator.

PMID- 28510734
TI  - Predictors of and outcomes following orthopaedic joint surgery in patients with
      early rheumatoid arthritis followed for 20 years.
AB  - Objectives: To analyse predictors and outcomes of major orthopaedic surgery in a
      cohort of RA patients followed for 20 years. Methods: Patients were recruited to
      the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical
      variables (including the HAQ and swollen and tender joint counts) were assessed
      at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients
      reported incident comorbidities and major orthopaedic joint surgery (replacement,
      synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and
      20. Baseline and time-varying predictors of orthopaedic surgery were assessed
      using a conditional risk set model, a type of multiple-failure survival analysis.
      Change in disability after surgery was assessed using weighted mixed-effects
      linear regression. Results: Of 589 RA patients [median age 56 years (IQR 45-68);
      66.7% women] recruited to the Norfolk Arthritis Register with at least one follow
      up, 102 reported a total of 180 major surgeries, with hip replacement being the
      most common (n = 68/180). Patients reporting major surgery had worse functional
      disability at all time points, but similar swollen/tender joint counts to those
      without major surgery. Each unit increase in HAQ score was associated with a
      doubling of the patient's risk of having surgery by the next assessment [hazard
      ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ
      scores after surgery than patients not undergoing surgery [beta = 0.17 (95% CI
      0.03, 0.32)]. Conclusion: HAQ was the strongest predictor of future major
      surgery. This supports the argument that HAQ should be included in routine
      clinical assessment.

PMID- 28510736
TI  - Go/no-go decision in anaesthesia: wide variation in risk tolerance amongst
      anaesthetists.
AB  - Background: The variability in risk tolerance in medicine is not well understood.
      Parallels are often drawn between aviation and anaesthesia. The aviation industry
      is perceived as culturally risk averse, and part of preflight checks involves a
      decision on whether the flight can operate. This is sometimes termed a go/no-go
      decision. This questionnaire study was undertaken to explore the equivalent go/no
      go decision in anaesthesia. We presented anaesthetists with a range of situations
      in which additional risk might be expected and asked them to decide whether they
      would proceed with the case. Methods: An electronic questionnaire was distributed
      to anaesthetic colleagues of all grades in one National Health Service Trust.
      Eleven scenarios, all drawn from critical incident data, were presented.
      Participants were invited to consider whether they would proceed, how they would
      modify their anaesthetic technique, and to predict whether a colleague with
      similar experience would make the same decision. Textual responses were analysed
      qualitatively. Results: The scenario response rate was 28%. Consultants were
      significantly more likely to proceed than trainees. In no scenario was there
      absolute agreement over whether to proceed, even in scenarios where national
      guidelines would suggest a case should be cancelled. Thematic analysis suggested
      a wide variability in what anaesthetists consider acceptable or professional
      behaviour. Conclusions: It is clear that safety decisions cannot be made in
      isolation and that clinicians must consider operational requirements, such as
      throughput, when making a go/no-go decision. The level of variability in decision
      making was surprising, particularly for scenarios that appeared to go against
      guidelines.

PMID- 28510737
TI  - Total haemoglobin mass, but not haemoglobin concentration, is associated with
      preoperative cardiopulmonary exercise testing-derived oxygen-consumption
      variables.
AB  - Background: Cardiopulmonary exercise testing (CPET) measures peak exertional
      oxygen consumption ( VO2peak ) and that at the anaerobic threshold ( VO2 at AT,
      i.e. the point at which anaerobic metabolism contributes substantially to overall
      metabolism). Lower values are associated with excess postoperative morbidity and
      mortality. A reduced haemoglobin concentration ([Hb]) results from a reduction in
      total haemoglobin mass (tHb-mass) or an increase in plasma volume. Thus, tHb-mass
      might be a more useful measure of oxygen-carrying capacity and might correlate
      better with CPET-derived fitness measures in preoperative patients than does
      circulating [Hb]. Methods: Before major elective surgery, CPET was performed, and
      both tHb-mass (optimized carbon monoxide rebreathing method) and circulating [Hb]
      were determined. Results: In 42 patients (83% male), [Hb] was unrelated to VO2 at
      AT and VO2peak ( r =0.02, P =0.89 and r =0.04, P =0.80, respectively) and
      explained none of the variance in either measure. In contrast, tHb-mass was
      related to both ( r =0.661, P <0.0001 and r =0.483, P =0.001 for VO2 at AT and
      VO2peak , respectively). The tHb-mass explained 44% of variance in VO2 at AT ( P
      <0.0001) and 23% in VO2peak ( P =0.001). Conclusions: In contrast to [Hb], tHb
      mass is an important determinant of physical fitness before major elective
      surgery. Further studies should determine whether low tHb-mass is predictive of
      poor outcome and whether targeted increases in tHb-mass might thus improve
      outcome.

PMID- 28510738
TI  - Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during
      cardiopulmonary bypass.
AB  - Background: High-dose heparin is used during cardiopulmonary bypass (CPB) to
      prevent thrombosis in the circuits used for extracorporeal circulation. The aim
      of this study was, initially, to develop a population
      pharmacokinetic/pharmacodynamic (PK/PD) model to assess the variability of PK/PD
      parameters and their correlation with the results of the routine haemostatic test
      activated clotting time (ACT) and thereafter to develop a Bayesian estimator
      enabling an individualized dosing strategy. Methods: Fifty consecutive patients
      undergoing cardiac surgery with CPB were included in the study. Heparin was
      administered as an initial bolus of 300 IU kg -1 followed by additional boluses
      of 5000 IU to maintain ACT <400 s. In total, 361 blood samples were collected.
      The PK and PD data were analysed using a non-linear mixed effect model. Results:
      A two-compartment model with a linear elimination link to an E max model best
      described heparin anti-factor Xa activities and ACT. Covariate analysis showed
      that body weight was positively correlated with clearance and central compartment
      volume. Inclusion of body weight with these parameters decreased their
      variability by 11 and 15%, respectively. The Bayesian estimator performed well in
      predicting individual parameters in an independent group of patients.
      Conclusions: A population PK/PD analysis of heparin during CPB, using a routine
      haemostatic test, shows that Bayesian estimation might help to predict ACT on the
      basis of only one or two blood samples.

PMID- 28510739
TI  - Comparison of preoperative and intraoperative assessment of aortic stenosis
      severity by echocardiography.
AB  - Background: General anaesthesia and surgically induced changes in cardiac loading
      conditions may alter flow across the aortic valve. This study examined how
      echocardiographic assessment of the severity of aortic stenosis (AS) changes
      during surgery. Methods: Patients who underwent aortic valve replacement for any
      severity of AS between July 2007 and June 2015 were identified. Peak velocities,
      mean gradients, and dimensionless indices (DI) measured with preoperative
      transthoracic echocardiography (TTE) were compared with those measured with
      intraoperative transoesophageal echocardiography (TOE). Additionally, agreement
      of preoperative and intraoperative grading of AS based on these measurements was
      assessed. Results: Data from 319 patients were analysed. On average,
      intraoperative TOE peak velocity and mean gradient were lower by 0.59 m s -1 and
      12.5 mm Hg, respectively ( P <0.0001), compared with preoperative TTE
      measurements, whereas the difference in mean DI was minimal at 0.008.
      Preoperative and intraoperative grades of AS severity (mild, moderate, and
      severe) by peak velocity, mean gradient, and DI agreed in 53.3, 53.7, and 83.3%
      of patients, respectively. The TOE grade of AS severity by peak velocity and mean
      gradient was at least one lower than the TTE grade in 45.1 and 42.7% of patients,
      respectively. Significantly fewer patients had their severity of AS reclassified
      based on DI ( P <0.0001). Conclusions: Intraoperative TOE peak velocities and
      mean gradients are often significantly lower than preoperative TTE measurements,
      leading to underestimation of AS severity in nearly half of our study patients.
      The DI is a more reliable measurement of AS severity in the intraoperative
      setting.

PMID- 28510740
TI  - Propofol-based anaesthesia versus sevoflurane-based anaesthesia for living donor
      kidney transplantation: results of the VAPOR-1 randomized controlled trial.
AB  - Background: Kidney transplantation is associated with harmful processes affecting
      the viability of the graft. One of these processes is associated with the
      phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely
      described strategy to attenuate ischaemia-reperfusion injury. We therefore
      conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a
      pilot project evaluating the influence of two anaesthetic regimens, propofol- vs
      sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living
      donor kidney transplantation. Methods: Sixty couples were randomly assigned to
      the following three groups: PROP (donor and recipient propofol), SEVO (donor and
      recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The
      primary outcome was renal injury reflected by urinary biomarkers. The follow-up
      period was 2 yr. Results: Three couples were excluded, leaving 57 couples for
      analysis. Concentrations of kidney injury molecule-1 (KIM-1), N -acetyl-beta- d 
      glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the
      first urine upon reperfusion showed no differences. On day 2, KIM-1
      concentrations were higher in SEVO [952.8 (interquartile range 311.8-1893.0) pg
      mmol -1 ] compared with PROP [301.2 (202.0-504.7) pg mmol -1 ]. This was the same
      for NAG: SEVO, 1.835 (1.162-2.457) IU mmol -1 vs PROP, 1.078 (0.819-1.713) IU
      mmol -1 . Concentrations of H-FABP showed no differences. Measured glomerular
      filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there
      was a difference in the acute rejection rate ( P =0.039). Post hoc testing
      revealed a difference between PROP (35%) and PROSE (5%; P =0.020). The difference
      between PROP and SEVO (11%) was not significant ( P =0.110). Conclusions: The
      SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor
      kidney transplantation on the second day after transplantation. This was not
      reflected in inferior graft outcome. Clinical trial registration: NCT01248871.

PMID- 28510741
TI  - Early or late fresh frozen plasma administration in newborns and small infants
      undergoing cardiac surgery: the APPEAR randomized trial.
AB  - Background: In newborns and small infants undergoing cardiac surgery with
      cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is
      reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming
      volume. This single-centre, randomized trial tested the hypothesis that the
      administration of FFP after CPB (late FFP group) is superior to FFP priming
      (early FFP group) in terms of postoperative bleeding and overall red blood cell
      (RBC) transfusion. Methods: Seventy-three infants weighing <10 kg were randomly
      allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36)
      or immediately after CPB ( n =37). The primary endpoint was a difference in
      postoperative blood loss; secondary endpoints included the amount of RBCs and FFP
      transfused through the first 48 postoperative hours. Results: All patients were
      included in the analysis. Patients in the late FFP arm had greater postoperative
      mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1
      (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The
      subgroup of cyanotic heart disease patients had comparable results, but with
      greater use of RBCs in the late FFP group. Conclusions: In infants undergoing
      cardiac surgery, FFP in the priming solution appears slightly superior to late
      administration in terms of postoperative bleeding. Clinical trial registration:
      www.ClinicalTrials.gov , NCT02738190.

PMID- 28510742
TI  - Drug safety in paediatric anaesthesia.
AB  - Life-threatening drug errors are more common in children than in adults. This is
      likely to be because of their variations in age and weight, combined with the
      occasional exposure of most anaesthetists to paediatric patients. Drug
      administration in anaesthesia is mostly undertaken by a single operator and thus
      represents a potentially greater risk compared with other areas of medicine. This
      increased risk is believed to be offset by anaesthetists working with only a
      limited number of drugs on a very frequent and repetitive basis. However, high
      rates of errors continue to be reported. Paediatric anaesthesia practice requires
      individual age- and weight-specific drug dose calculations and is therefore
      without a 'familiar' or 'usual' dose. The aim of this narrative systematic review
      of existing recommendations and current evidence of preventive strategies is to
      identify measures to enhance the safety and quality of drug administration in
      paediatric anaesthesia. This review collates and grades the evidence of such
      interventions and recommendations and assesses their feasibility. Most highly
      effective available measures require low or limited costs and labour. The
      presented solutions should, therefore, achieve a high level of acceptance and
      contribute significantly to safety and quality of care in paediatric anaesthesia.

PMID- 28510743
TI  - Critical airways, critical language.

PMID- 28510744
TI  - It's not about the bike: enhancing oxygen delivery.

PMID- 28510745
TI  - Neural network imaging to characterize brain injury in cardiac procedures: the
      emerging utility of connectomics.
AB  - Cognitive dysfunction is a poorly understood but potentially devastating
      complication of cardiac surgery. Clinically meaningful assessment of cognitive
      changes after surgery is problematic because of the absence of a means to obtain
      reproducible, objective, and quantitative measures of the neural disturbances
      that cause altered brain function. By using both structural and functional
      connectivity magnetic resonance imaging data to construct a map of the inter
      regional connections within the brain, connectomics has the potential to increase
      the specificity and sensitivity of perioperative neurological assessment,
      permitting rational individualized assessment and improvement of surgical
      techniques.

PMID- 28510746
TI  - Engaging in risky business: is it time to rethink risk tolerance in anaesthesia?

PMID- 28510747
TI  - 'Failed supraglottic airway': an algorithm for suboptimally placed supraglottic
      airway devices based on videolaryngoscopy.

PMID- 28510748
TI  - Volatile anaesthetics and organ protection in kidney transplantation: finally, a
      randomized controlled trial!

PMID- 28510749
TI  - Dead or dying? Pulseless electrical activity during trauma resuscitation.

PMID- 28510750
TI  - Medication errors in paediatric anaesthesia: the hidden part of the iceberg.

PMID- 28510751
TI  - Anaesthetic considerations for hybrid atrial fibrillation surgery.

PMID- 28510752
TI  - Real-time ultrasound-guided paramedian spinal anaesthesia: evaluation of the
      efficacy and the success rate of single needle pass.

PMID- 28510753
TI  - A different use of visual analytic techniques in anaesthetics.

PMID- 28510754
TI  - The diagnostic challenge of a vitamin K antagonist with dabigatran use triggering
      massive intracranial haemorrhage.

PMID- 28510755
TI  - Suturing central venous catheters.

PMID- 28510756
TI  - Classification of videolaryngoscopes is crucial.

PMID- 28510757
TI  - An unusual sidestream capnogram.

PMID- 28510758
TI  - Reply-stopping antithrombotics during regional anaesthesia and eye surgery:
      crying wolf?

PMID- 28510760
TI  - What factors hinder the decision-making process for women with cancer and
      contemplating fertility preservation treatment?
AB  - BACKGROUND: Although fertility preservation (FP) treatment options have
      increased, the existing evidence suggests that many women with cancer do not feel
      well supported in making these decisions, but find them stressful and complex and
      fail to take up fertility care at this crucial time. Whilst existing reviews have
      all made important contributions to our understanding of the FP decision-making
      process, none of them examine solely and specifically these processes for women
      of reproductive age with a diagnosis of any cancer, leaving a gap in the
      knowledge base. Given the expectation that care is patient-centred, our review
      aims to address this gap which may be of help to those managing patients
      struggling to make difficult decisions in the often brief period before
      potentially sterilizing cancer treatment is started. OBJECTIVE AND RATIONALE:
      Underpinning this narrative review was the question 'What factors hinder the
      decision-making process for women with any cancer and contemplating FP
      treatment?' Our objectives were to (i) assess and summarize this existing
      literature, (ii) identify the factors that hinder this decision-making process,
      (iii) explore to what extent these factors may differ for women choosing
      different methods of FP and (iv) make recommendations for service delivery and
      future research. SEARCH METHODS: A systematic search of the medical and social
      science literature from the 1 January 2005 up to the end of January 2016 was
      carried out using three electronic databases (Web of Science (PubMed), Ovid SP
      Medline and CINAHL via Ebsco). Included in the review were quantitative,
      qualitative and mixed-method studies. Reference lists of relevant papers were
      also hand searched. From the 983 papers identified, 46 papers were included.
      Quality assessment was undertaken using the Mixed Methods Appraisal Tool and
      thematic analysis was used to analyse the data. OUTCOMES: From the analysis, 6
      key themes with 15 sub-themes emerged: (i) fertility information provision (lack
      of information, timing of the information, patient-provider communication); (ii)
      fear concerning the perceived risks associated with pursuing FP (delaying cancer
      treatment, aggravating a hormone positive cancer and consequences of a future
      pregnancy); (iii) non-referral from oncology (personal situation, having a
      hormone positive cancer, FP not a priority and transition between service
      issues); (iv) the dilemma (in survival mode, whether to prioritize one treatment
      over another); (v) personal situation (parity, relationship status) and (iv)
      costs (financial concerns). WIDER IMPLICATIONS: This review has found that a wide
      range of internal and external factors impact the FP decision-making process. Key
      external issues related to current service delivery such as the provision and
      timing of FP information, and lack of referral from oncology to the fertility
      clinic. However, internal issues such as women's fears concerning the perceived
      risks associated with pursuing FP also hindered decision-making but these 'risks'
      were typically overestimated and non-evidence based. These findings suggest that
      the implementation of a range of decision support interventions may be of benefit
      within the clinical care pathway of FP and cancer. Women would benefit from the
      provision of more evidence-based FP information, ideally received at cancer
      diagnosis, in advance of seeing a fertility specialist, for example through the
      implementation of patient decision aids. Healthcare professionals in both
      oncology and fertility services may also benefit from the implementation of
      training programmes and educational tools targeted at improving the communication
      skills needed to improve collaborative decision-making and deliver care that is
      patient-centred. Exploration of the current barriers, both intellectual and
      practical, that prevent some patients from accepting FP will help care providers
      to do better for their patients in the future. Finally, the extent to which a
      poorer prognosis and moral, ethical and religious beliefs influence the FP
      decision-making process also warrant further research.

PMID- 28510759
TI  - An intact Mcm10 coiled-coil interaction surface is important for origin melting,
      helicase assembly and the recruitment of Pol-alpha to Mcm2-7.
AB  - Mcm10 is an essential eukaryotic factor required for DNA replication. The
      replication fork helicase is composed of Cdc45, Mcm2-7 and GINS (CMG). DDK is an
      S-phase-specific kinase required for replication initiation, and the DNA primase
      polymerase in eukaryotes is pol alpha. Mcm10 forms oligomers in vitro, mediated
      by the coiled-coil domain at the N-terminal region of the protein. We
      characterized an Mcm10 mutant at the N-terminal Domain (NTD), Mcm10-4A, defective
      for self-interaction. We found that the Mcm10-4A mutant was defective for
      stimulating DDK phosphorylation of Mcm2, binding to eighty-nucleotide ssDNA, and
      recruiting pol alpha to Mcm2-7 in vitro. Expression of wild-type levels of mcm10
      4A resulted in severe growth and DNA replication defects in budding yeast cells,
      with diminished DDK phosphorylation of Mcm2. We then expressed the mcm10-4A in
      mcm5-bob1 mutant cells to bypass the defects mediated by diminished stimulation
      of DDK phosphorylation of Mcm2. Expression of wild-type levels of mcm10-4A in
      mcm5-bob1 mutant cells resulted in severe growth and DNA replication defects,
      along with diminished RPA signal at replication origins. We also detected
      diminished GINS and pol-alpha recruitment to the Mcm2-7 complex. We conclude that
      an intact Mcm10 coiled-coil interaction surface is important for origin melting,
      helicase assembly, and the recruitment of pol alpha to Mcm2-7.

PMID- 28510761
TI  - The diversity of CO2-concentrating mechanisms in marine diatoms as inferred from
      their genetic content.
AB  - Marine diatoms are one of the most ecologically significant primary producers in
      the ocean. Most diatoms use a CO2-concentrating mechanism (CCM) to overcome the
      scarcity of CO2 in the ocean and limitations of the carbon-fixing enzyme Rubisco.
      However, the CCMs in model diatoms differ substantially in their genetic make-up
      and structural organization. To assess the extent of CCM diversity in marine
      diatoms more generally, we analyzed genome and transcriptome data from 31 diatom
      strains to identify putative CCM genes, examine the overall CCM architecture, and
      study CCM development in the context of the evolutionary history of these
      diatoms. Key CCM genes [carbonic anhydrases (CAs) and solute carrier 4 (SLC4)
      bicarbonate transporters] identified in the diatoms were placed into groups of
      likely orthologs by sequence similarity (OrthoMCL) and phylogenetic methods.
      These analyses indicated that diatoms seem to share similar HCO3- transporters,
      but possess a variety of CAs that have either undergone extensive diversification
      within the diatom lineage or have been acquired through horizontal gene transfer.
      Hierarchical clustering of the diatom species based on their CCM gene content
      suggests that CCM development is largely congruent with evolution of diatom
      species, despite some notable differences in CCM genes even among closely related
      species.

PMID- 28510762
TI  - Physician burnout, work engagement and the quality of patient care.
AB  - Background: Research suggests that burnout in physicians is associated with
      poorer patient care, but evidence is inconclusive. More recently, the concept of
      work engagement has emerged (i.e. the beneficial counterpart of burnout) and has
      been associated with better care. Evidence remains markedly sparse however. Aims:
      To examine the associations of burnout and work engagement with physicians' self
      perceived quality of care. Methods: We drew on cross-sectional data from
      physicians in Germany. We used a six-item version of the Maslach Burnout
      Inventory measuring exhaustion and depersonalization. We employed the nine-item
      Utrecht Work Engagement Scale to assess work engagement and its subcomponents:
      vigour, dedication and absorption. We measured physicians' own perceptions of
      their quality of care by a six-item instrument covering practices and attitudes.
      We used continuous and categorized dependent and independent variables in linear
      and logistic regression analyses. Results: There were 416 participants. In
      multivariable linear regression analyses, increasing burnout total scores were
      associated with poorer perceived quality of care [unstandardized regression
      coefficient (b) = 0.45, 95% confidence interval (CI) 0.37, 0.54]. This
      association was stronger for depersonalization (b = 0.37, 95% CI 0.29, 0.44) than
      for exhaustion (b = 0.26, 95% CI 0.18, 0.33). Increasing work engagement was
      associated with higher perceived quality care (b for the total score = -0.20, 95%
      CI -0.28, -0.11). This was confirmed for each subcomponent with stronger
      associations for vigour (b = -0.21, 95% CI -0.29, -0.13) and dedication (b = 
      0.16, 95% CI -0.24, -0.09) than for absorption (b = -0.12, 95% CI -0.20, -0.04).
      Logistic regression analyses yielded comparable results. Conclusions: Physician
      burnout was associated with self-perceived poorer patient care, while work
      engagement related to self-reported better care. Studies are needed to
      corroborate these findings, particularly for work engagement.

PMID- 28510763
TI  - Reply to: "Periodic Limb Movements During Sleep and White Matter MRI
      Hyperintensity in Minor Stroke or TIA".

PMID- 28510764
TI  - Periodic Limb Movements During Sleep and White Matter MRI Hyperintensity in Minor
      Stroke or TIA.

PMID- 28510765
TI  - Research Priorities in the Area of Sleep/Circadian Rhythm and Aging Research:
      Commentary on "Report and Research Agenda of the American Geriatrics Society and
      National Institute on Aging Bedside-to-Bench Conference on Sleep, Circadian
      Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health, and
      Functioning".

PMID- 28510768
TI  - Corrigenda.

PMID- 28510767
TI  - Corrigenda.

PMID- 28510766
TI  - Detection of 3,3'-Dichlorobiphenyl in Human Maternal Plasma and Its Effects on
      Axonal and Dendritic Growth in Primary Rat Neurons.
AB  - 3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is
      increasingly detected in environmental samples. While more highly chlorinated PCB
      congeners are known developmental neurotoxicants, nothing is known about the
      potential developmental neurotoxicity of PCB 11. To address this critical data
      gap, we measured PCB 11 levels in human maternal plasma and quantified the
      effects of PCB 11 and its major metabolites on morphometric parameters of
      neuronal connectivity in cultured primary neurons. Mass spectrometry analyses of
      plasma from 241 pregnant women enrolled in the MARBLES study (University of
      California, Davis) detected PCB 11 in all samples at concentrations ranging from
      0.005 to 1.717 ng/ml. Morphometric analyses of primary neuron-glia co-cultures
      dissociated from the neocortices or hippocampi of neonatal Sprague Dawley rats
      exposed to vehicle or concentrations ranging from 1 attamolar (aM) to 1
      micromolar (uM) of PCB 11, OH-PCB 11, or PCB 11 sulfate indicated that PCB 11 and
      both metabolites significantly increased axonal and dendritic growth in cortical
      and hippocampal pyramidal neurons. PCB 11 significantly altered neuronal
      morphogenesis at concentrations as low as 1 femtomolar (fM), which is ~0.22
      ng/ml. These data suggest the potential for the developing human brain to be
      exposed to PCB 11, and demonstrate that environmentally relevant levels of PCB 11
      alter axonal and dendritic growth in neuronal cell types critically involved in
      cognitive and higher-order behaviors. These findings identify PCB 11 as a
      potential environmental risk factor for adverse neurodevelopmental outcomes in
      humans.

PMID- 28510769
TI  - Comparison of Objective and Subjective Techniques of Strabismus Measurement in
      Adults With Normal Retinal Correspondence.
AB  - PURPOSE: Accurate measurement of strabismus is vital to proper diagnosis and
      treatment. Objective and subjective measurement techniques can be used. The
      authors hypothesized that subjective measurement techniques would measure larger
      deviations than objective ones. METHODS: Adults with strabismus, visual acuity
      greater than 20/50 in each eye, and normal retinal correspondence were measured
      in primary gaze at distance and near using the alternate prism and cover test and
      the red glass test. RESULTS: Seventy-three patients were prospectively enrolled.
      Objective mean deviations were 9.1 (distance horizontal), 5.1 (distance
      vertical), 10.0 (near horizontal), and 2.6 (near vertical) prism diopters (PD).
      Subjective mean deviations were 10.2 (distance horizontal), 6.8 (distance
      vertical), 12.2 (near horizontal), and 3.2 (near vertical) PD. Subjective
      measurements were larger by a statistically significant margin and were more
      likely to show the presence of a vertical deviation not measured objectively (19
      occurrences vs 2 at near, P = .008; 15 occurrences vs 0 at distance, P = .004).
      The measured deviations were within 5 PD horizontally and 3 PD vertically most of
      the time (range: 66.7% to 83.6%). CONCLUSIONS: The red glass test was more likely
      to measure a larger deviation at distance and near and to identify a vertical
      deviation not seen objectively at both distance and near. The mean difference
      between the tests was usually not large enough to affect surgical treatment, but
      could potentially result in different amounts of prescribed prism for patients
      treated optically. [J Pediatr Ophthalmol Strabismus. 2017;54(4):216-220.].

PMID- 28510770
TI  - Inferior Oblique Overaction: Anterior Transposition Versus Myectomy.
AB  - PURPOSE: To compare the efficacy of inferior oblique myectomy and anterior
      transposition for correcting inferior oblique overaction (IOOA). METHODS: This
      retrospective study was conducted on 56 patients with IOOA who had either
      myectomy or anterior transposition of the inferior oblique muscle from 2010 to
      2015. The authors compared preoperative and postoperative inferior oblique muscle
      function grading (-4 to +4) as the main outcome measure and vertical and
      horizontal deviation, dissociated vertical deviation (DVD), and A- and V-pattern
      between the two surgical groups as secondary outcomes. RESULTS: A total of 99
      eyes of 56 patients with a mean age of 5.9 +/- 6.5 years were included (47 eyes
      in the myectomy group and 52 eyes in the anterior transposition group). There
      were no differences in preoperative best corrected visual acuity, amblyopia,
      spherical equivalent, and primary versus secondary IOOA between the two groups.
      Both surgical procedures were effective in reducing IOOA and satisfactory results
      were similar between the two groups: 61.7% and 67.3% in the myectomy and anterior
      transposition groups, respectively (P = .56). After adjustment for the
      preoperative DVD, there was no statistically significant difference between the
      two groups postoperatively. The preoperative hypertropia was 6 to 14 and 6 to 18
      prism diopters (PD) in the myectomy and anterior transposition groups,
      respectively. After surgery, no patient had a vertical deviation greater than 5
      PD. CONCLUSIONS: Both the inferior oblique myectomy and anterior transposition
      procedures are effective in reducing IOOA with similar satisfactory results. DVD
      and hypertropia were also corrected similarly by these two surgical procedures.
      [J Pediatr Ophthalmol Strabismus. 2017;54(4):232-237.].

PMID- 28510771
TI  - Inability of Open-Field Autorefraction to Eliminate Accommodation in
      Preschoolers.
AB  - PURPOSE: To evaluate the effectiveness of the Shin-Nippon NVision-K 5001
      autorefractometer (Rexxam Co. Ltd., Osaka, Japan) (also branded as the Grand
      Seiko WR-5100K; Grand Seiko Co. Ltd., Hiroshima, Japan) based on the open-field
      refractometry principle in refractive measurements of preschool children and to
      determine its ability to eliminate accommodation adequately. METHODS: The
      refractive results of 114 preschool children who presented to the ophthalmology
      outpatient department for screening were evaluated. The measurements were
      obtained before and after cycloplegia with the Shin-Nippon NVision-K 5001
      autorefractometer and after cycloplegia with retinoscopy, which is the gold
      standard. The results underwent vectorial transformation to produce the spherical
      equivalent (M) and two Jackson cross-cylinder (J0 and J45) values. All results
      were then subjected to statistical analysis. The difference between the
      measurements was evaluated with repeated measures analysis of variance. RESULTS:
      Included in the study were 106 preschool children (51 boys and 55 girls). The
      mean age was 5.3 +/- 0.9 years (range: 3 to 6 years). Although statistically
      significantly more myopic results were obtained with non-cycloplegic measurements
      using the Shin-Nippon NVision-K 5001 autorefractometer (P < .001), no difference
      was observed in cylindrical values (P > .05). Cycloplegic J0 measurements were
      significantly lower (P < .001), but no difference was found between J45 values
      before and after cycloplegia (P > .05). CONCLUSIONS: The Shin-Nippon NVision-K
      5001/Grand Seiko WR-5100K open-field autorefractometer seems to be inadequate in
      eliminating accommodation in childhood. Measurements under cycloplegia continue
      to be the best method to ensure accurate results. [J Pediatr Ophthalmol
      Strabismus. 2017;54(5):311-318.].

PMID- 28510772
TI  - Prevalence, Incidence, and Risk Factors for the Development of Glaucoma in
      Patients With Aniridia.
AB  - PURPOSE: To assess the prevalence, incidence, and risk factors for the
      development of glaucoma in patients with aniridia. METHODS: Retrospective
      analysis of case records of patients diagnosed as having congenital aniridia
      between January 1986 and December 2011 was performed. Patients with a follow-up
      of more than 12 months were included. RESULTS: Ninety-one patients (180 eyes)
      with the diagnosis of aniridia were identified from the case records. Two eyes
      were excluded from the final analysis; one had developed phthisis and the other
      had been enucleated. Seventy-four patients (81.3%) were younger than 18 years at
      initial presentation. The prevalence of glaucoma at presentation was 28.8%, which
      could be further categorized as ocular hypertension in 19 eyes (10.5%) and
      glaucoma in 33 eyes (18.3%). Thirty-one eyes (28.4%) developed elevated
      intraocular pressure (IOP) during the follow-up period: ocular hypertension in 23
      eyes (17.9%) and glaucoma in 8 eyes (6.25%). The mean IOP at the time of
      diagnosis was 33.9 +/- 8.6 mm Hg (range: 24 to 60 mm Hg). The mean duration of
      follow-up was 8.1 +/- 5.7 years (range: 1 to 28 years). The cumulative
      probability of developing elevated IOP was 4% at the end of 8 years of follow-up;
      this increased to 88% at the end of 28 years of follow-up. Univariate logistic
      regression analysis identified higher baseline IOP (odds ratio [OR]: 1.2; 95%
      confidence interval [CI]: 1.2 to 1.4) and limbal stem cell deficiency (OR: 2.8;
      95% CI: 1.4 to 5.6) as significant risk factors for the development of elevated
      IOP. Higher baseline IOP remained significant on multivariate analysis (OR: 1.2;
      95% CI: 1.2 to 1.4). CONCLUSIONS: Glaucoma occurs in a substantial proportion of
      patients with aniridia. Eyes with increased IOP at baseline are at a higher risk.
      [J Pediatr Ophthalmol Strabismus. 2017;54(4):250-255.].

PMID- 28510773
TI  - Evaluation of the Role of Monocular Video Game Play as an Adjuvant to Occlusion
      Therapy in the Management of Anisometropic Amblyopia.
AB  - PURPOSE: To evaluate the role of monocular video game play as an adjuvant to
      occlusion therapy in the treatment of anisometropic amblyopia. METHODS: In a
      prospective randomized study design, 68 children with ages ranging from 6 to 14
      years who had anisometropic amblyopia with a best corrected visual acuity (BCVA)
      in the amblyopic eye of better than 6/36 and worse than 6/12 and no manifest
      strabismus were recruited. They were randomly allocated into two groups: 34
      children received 1 hour per day of video game play for the first month plus 6
      hours per day of occlusion therapy (video game and occlusion group) and 34
      children received 6 hours per day of occlusion therapy alone (occlusion only
      group). Patients were then evaluated at baseline and 1 and 3 months after
      treatment for BCVA, stereoacuity, and contrast sensitivity. RESULTS: In the video
      game and occlusion group, BCVA improved from 0.61 +/- 0.12 logarithm of the
      minimum angle of resolution (logMAR) at baseline to 0.51 +/- 0.14 logMAR (P =
      .001) at 1 month and 0.40 +/- 0.15 logMAR (P = .001) at 3 months. In the
      occlusion only group, BCVA improved from 0.65 +/- 0.09 logMAR at baseline to 0.60
      +/- 0.10 logMAR (P = .001) at 1 month and 0.48 +/- 0.10 logMAR (P = .001) at 3
      months. There was significantly more improvement in the video game and occlusion
      group compared to the occlusion only group (P = .003 at 1 month and P = .027 at 3
      months). CONCLUSIONS: Video game play plus occlusion therapy enhances the visual
      recovery in anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus.
      2017;54(4):244-249.].

PMID- 28510774
TI  - Combined Surgery for Simultaneous Treatment of Congenital Ptosis and Coexisting
      Strabismus.
AB  - PURPOSE: To evaluate the clinical outcomes of single-stage surgery for treatment
      of patients with congenital ptosis and coexisting strabismus. METHODS: A
      retrospective analysis was performed on 10 patients (17 eyes) with congenital
      ptosis and coexisting strabismus. Patients were treated with levator resection or
      frontalis suspension for ptosis and ocular muscle surgery for strabismus,
      performed as a single-stage procedure. Levator resection was performed in 9
      patients (15 eyes) and frontalis muscle flap suspension was performed in 1
      patient (2 eyes) with blepharophimosis. Seven patients (11 eyes) simultaneously
      underwent exotropia correction, and inferior oblique myectomy was performed in 3
      patients (3 eyes) with congenital superior oblique palsy. RESULTS: Satisfactory
      efficacy of single-stage surgery for correction of congenital ptosis and
      coexisting strabismus was achieved without complications. CONCLUSIONS:
      Comprehensive preoperative examination is vital to determine the appropriate
      diagnosis and guide surgical decision-making. Single-stage surgery for congenital
      ptosis and coexisting strabismus is effective and a shortened treatment period is
      beneficial to patients. [J Pediatr Ophthalmol Strabismus. 2017;54(5):288-294.].

PMID- 28510775
TI  - Progression of High Anisometropia in Children.
AB  - PURPOSE: To investigate the onset and rate of progression of high anisometropia
      in myopic children younger than 13 years. METHODS: A retrospective study was
      performed on children with anisometropia younger than 13 years with myopia of
      more than 4.00 diopters (D) in the more ametropic eye and a difference in
      spherical equivalent refraction of 4.00 D between both eyes. All children had a
      complete ophthalmologic examination, including measurement of visual acuity and
      cycloplegic refraction every 3 to 6 months for at least 5 years. Change in the
      spherical equivalent and the cylindrical error for both eyes and changes in the
      difference in spherical equivalent refraction between both eyes were calculated
      for each patient at each visit. Linear, polynomial, logarithmic, and exponential
      fitting models were tested for both eyes and for the anisometropic difference
      between both eyes. The regression line with the greatest R2 value was considered
      best fit. RESULTS: Sixty-three patients fulfilled the inclusion criteria. The
      more ametropic eye grew in a regular fashion during the first 2 years of life,
      followed by a rapid decrease in the rate of growth to become almost stable after
      4 years of age. The increase in myopia best fit a third-degree polynomial (cubic)
      model (R2 = 0.98). The less ametropic eye showed only a small increase in myopia
      during the follow-up period. The anisometropic difference between both eyes
      increased gradually during the first 2 years, then remained stable. CONCLUSIONS:
      High anisometropic myopia progresses rapidly in the first few years of life
      before becoming stable. [J Pediatr Ophthalmol Strabismus. 2017;54(5):282-286.].

PMID- 28510776
TI  - Patient Characteristics and Surgical Approach Impacting Simultaneous to Alternate
      Prism Cover Test Disparity After Exotropia Surgery: A Quantitative Look at the
      Difference in Motor Outcomes.
AB  - PURPOSE: To investigate the relationship between simultaneous prism and cover
      test (SPCT) and alternate prism and cover test (APCT) outcomes after exotropia
      surgery, and to identify characteristics associated with significant disparity
      between them. METHODS: Review of sensorimotor outcomes 2 to 6 months after
      exotropia surgery identified patients with alignment documented by both SPCT and
      APCT at the same examination. Two hundred seventy-four and 319 patients had both
      measurements recorded at distance and near, respectively. Correlation between the
      SPCT and APCT and range of APCT when the SPCT measurement was zero were
      determined. Patient characteristics studied for association with a difference
      between the SPCT and APCT exceeding known APCT test-retest variability included
      age, visual acuity, fusion, intermittency, pattern, preoperative and
      postoperative angle, and treatment with or without medial rectus resection.
      RESULTS: SPCT and APCT outcomes were strongly correlated (P < .001),
      significantly different (P < .001), and linearly related. The percentage of
      patients who were orthotropic (SPCT = 0) was 76% at distance and 80% at near.
      Misalignment of 10 prism diopters (PD) or less by the APCT was present in 92% of
      orthotropic patients at distance and 84% at near. Surgery without medial rectus
      resection (P = .015), larger preoperative angle (P = .003), intermittent
      exotropia (P = .028), and postoperative exotropia rather than esotropia (P <
      .001) were associated with a significant SPCT-APCT difference. CONCLUSIONS:
      Although a greater postoperative SPCT-APCT disparity was confirmed for patients
      with intermittent exotropia, it also independently associated with a larger
      preoperative deviation and surgery without medial rectus resection. Performing
      medial rectus resection, a surgeon's prerogative, provides more apparently
      consistent postoperative alignment characterized by less SPCT-APCT disparity. [J
      Pediatr Ophthalmol Strabismus. 2017;54(4):222-230.].

PMID- 28510777
TI  - Anatomical Characterization of the Nasolacrimal Canal Based on Computed
      Tomography in Children With Complex Congenital Nasolacrimal Duct Obstruction.
AB  - PURPOSE: To characterize anatomical variations of the nasolacrimal canal in
      patients with complex congenital nasolacrimal duct obstruction. METHODS:
      Retrospective case series of 25 children with congenital nasolacrimal duct
      obstruction. All children had failed probings and were examined by computed
      tomography. An analysis of imaging data is presented. RESULTS: Anomalous
      development of the nasolacrimal canal was confirmed on computed tomography. Two
      main types of malformations were observed: fundamental (20 patients) and special
      (5 patients). In the fundamental type, the upper portion of the nasolacrimal
      canal was relatively normal and became significantly stenotic, or even atretic,
      at the middle and terminal segments. In the special type, the upper portion of
      the nasolacrimal duct was malformed. Only the special type showed an association
      with systemic abnormalities. In patients with unilateral fundamental type
      malformation (11 patients), the transverse and anteroposterior diameters of the
      upper segment of the nasolacrimal canal on the affected side were significantly
      larger than that of the normal side (P = .000). The height of the nasolacrimal
      canal on the normal side was significantly larger than that of the affected side
      (P = .000). CONCLUSION: Computed tomography is useful for delineation of
      anatomical characteristics of the nasolacrimal canal and to diagnose nasolacrimal
      canal malformation. Malformed nasolacrimal canals are of two main types:
      fundamental and special. Hydrostatic pressure in the lacrimal duct appears to the
      underlying mechanism as enlargement of the nasolacrimal canal in the unilateral
      fundamental type. [J Pediatr Ophthalmol Strabismus. 2017;54(4):238-243.].

PMID- 28510780
TI  - Design and Testing of a New Diatom-Based Index for Heavy Metal Pollution.
AB  - The Tinto and Odiel river basins (SW Spain) are known worldwide for their unique
      water characteristics. Such uniqueness is a consequence of their flow through the
      Iberian Pyrite Belt (an area rich in metal sulphides) and the mining activities
      in the basins. A process of sulphide oxidation occurs in this region, which
      acidifies the water and increases the amount of heavy metals in it. As a result,
      the rivers suffer the so-called "acid mine drainage" (AMD). Traditional biotic
      diatom-based indexes (IPS, IBD, EPI-D, etc.) do not take into account the
      pollution caused by AMD. The purpose of this paper is to develop a new diatom
      based index which can serve as a useful and quick monitoring tool. Such tool must
      reflect the level of AMD while being user friendly. We present the development
      and validation of the ICM (Indice de Contaminacion por Metales or Metal Pollution
      Index). ICM demonstrated to meet successfully the above criteria and, therefore,
      can assess water quality in the Tinto and Odiel Rivers. In addition, ICM was
      applied with satisfactory results in the Guadiamar River (SW Spain), which was
      subjected to AMD too. Thus, we propose to make use of it in any other basin with
      the same type of pollution.

PMID- 28510779
TI  - Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent
      stem cells.
AB  - The liver is a dynamic organ which is both multifunctional and highly
      regenerative. A major role of the liver is to process both endo and xenobiotics.
      Cigarettes are an example of a legal and widely used drug which can cause major
      health problems for adults and constitute a particular risk to the foetus, if the
      mother smokes during pregnancy. Cigarette smoke contains a complex mixture of
      thousands of different xenobiotics, including nicotine and polycyclic aromatic
      hydrocarbons. These affect foetal development in a sex-specific manner, inducing
      sex-dependant molecular responses in different organs. To date, the effect of
      maternal smoking on the foetal liver has been studied in vitro using cell lines,
      primary tissue and animal models. While these models have proven to be useful,
      poor cell phenotype, tissue scarcity, batch-to-batch variation and species
      differences have led to difficulties in data extrapolation toward human
      development. Therefore, in this study we have employed hepatoblasts, derived from
      pluripotent stem cells, to model the effects of xenobiotics from cigarette smoke
      on human hepatocyte development. Highly pure hepatocyte populations (>90%) were
      produced in vitro and exposed to factors present in cigarette smoke. Analysis of
      ATP levels revealed that, independent of the sex, the majority of smoking
      derivatives tested individually did not deplete ATP levels below 50%. However,
      following exposure to a cocktail of smoking derivatives, ATP production fell
      below 50% in a sex-dependent manner. This was paralleled by a loss metabolic
      activity and secretory ability in both female and male hepatocytes.
      Interestingly, cell depletion was less pronounced in female hepatocytes, whereas
      caspase activation was ~twofold greater, indicating sex differences in cell death
      upon exposure to the smoking derivatives tested.

PMID- 28510783
TI  - Transcranial Doppler monitoring guided by cranial two-dimensional
      ultrasonography.

PMID- 28510781
TI  - 5-Azacytidine mediated reactivation of silenced transgenes in potato (Solanum
      tuberosum) at the whole plant level.
AB  - KEY MESSAGE: Transient 5-azacytidine treatment of leaf explants from potato
      plants with transcriptionally silenced transgenes allows de novo regeneration of
      plants with restored transgene expression at the whole plant level. Transgenes
      introduced into plant genomes frequently become silenced either at the
      transcriptional or the posttranscriptional level. Transcriptional silencing is
      usually associated with DNA methylation in the promoter region. Treatments with
      inhibitors of maintenance DNA methylation were previously shown to allow
      reactivation of transcriptionally silenced transgenes in single cells or tissues,
      but not at the whole plant level. Here we analyzed the effect of DNA methylation
      inhibitor 5-azacytidine (AzaC) on the expression of two silenced reporter genes
      encoding green fluorescent protein (GFP) and neomycin phosphotransferase (NPTII)
      in potato plants. Whereas no obvious reactivation was observed in AzaC-treated
      stem cuttings, transient treatment of leaf segments with 10 MUM AzaC and
      subsequent de novo regeneration of shoots on the selective medium with kanamycin
      resulted in the production of whole plants with clearly reactivated expression of
      previously silenced transgenes. Reactivation of nptII expression was accompanied
      by a decrease in cytosine methylation in the promoter region of the gene. Using
      the plants with reactivated GFP expression, we found that re-silencing of this
      transgene can be accidentally triggered by de novo regeneration. Thus, testing
      the incidence of transgene silencing during de novo regeneration could be a
      suitable procedure for negative selection of transgenic lines (insertion events)
      which have an inclination to be silenced. Based on our analysis of non-specific
      inhibitory effects of AzaC on growth of potato shoots in vitro, we estimated that
      AzaC half-life in the culture media is approximately 2 days.

PMID- 28510782
TI  - Memory-guided force control in healthy younger and older adults.
AB  - Successful performance of a memory-guided motor task requires participants to
      store and then recall an accurate representation of the motor goal. Further,
      participants must monitor motor output to make adjustments in the absence of
      visual feedback. The goal of this study was to examine memory-guided grip force
      in healthy younger and older adults and compare it to performance on behavioral
      tasks of working memory. Previous work demonstrates that healthy adults decrease
      force output as a function of time when visual feedback is not available. We
      hypothesized that older adults would decrease force output at a faster rate than
      younger adults, due to age-related deficits in working memory. Two groups of
      participants, younger adults (YA: N = 32, mean age 21.5 years) and older adults
      (OA: N = 33, mean age 69.3 years), completed four 20-s trials of isometric force
      with their index finger and thumb, equal to 25% of their maximum voluntary
      contraction. In the full-vision condition, visual feedback was available for the
      duration of the trial. In the no vision condition, visual feedback was removed
      for the last 12 s of each trial. Participants were asked to maintain constant
      force output in the absence of visual feedback. Participants also completed tasks
      of word recall and recognition and visuospatial working memory. Counter to our
      predictions, when visual feedback was removed, younger adults decreased force at
      a faster rate compared to older adults and the rate of decay was not associated
      with behavioral performance on tests of working memory.

PMID- 28510784
TI  - Effects of acute and chronic hypoxia on acid-base regulation, hematology, ion,
      and osmoregulation of juvenile American paddlefish.
AB  - Despite the increasing prevalence of hypoxia in natural habitats occupied by the
      American paddlefish, basal bony fish, and ram ventilator, information about its
      response to hypoxia is scarce. To understand the physiological and biochemical
      responses of juvenile paddlefish (~150 g) to acute (<24 h) and chronic hypoxia
      (>=24 h), blood oxygen transport, blood acid-base balance, and metabolic stress
      were evaluated under four different partial pressures of oxygen [pO2; normoxia
      (148 mmHg), mild hypoxia (89 mmHg), moderate hypoxia (59 mmHg), and extreme
      hypoxia (36 mmHg)], all at 21  degrees C. Arterial blood samples were collected
      from paddlefish after they had been exposed to treatments for 0.25, 2, 6, 24, and
      72 h, and analyzed for hematocrit, pO2, total oxygen content, oxygen saturation,
      pCO2, pH, hemoglobin, Na+, K+, Ca2+, Cl-, glucose, and lactate. Mild hypoxia only
      caused a reduction in blood pO2 and oxygen saturation. Both acute and chronic
      moderate and extreme hypoxia caused a decrease in blood pH, pO2, total oxygen
      content, plasma Na+, and Cl- at all time points. Acute moderate and extreme
      hypoxia resulted in an increase in blood pCO2, plasma glucose, lactate, and
      hematocrit. Chronic exposure to moderate hypoxia resulted in an increase in
      plasma lactate, red blood cell count, and hemoglobin. This study shows that
      paddlefish are able to physiologically compensate for mild hypoxia, but exhibit
      secondary stress responses and are unable to return to homeostasis when exposed
      to both acute and chronic moderate hypoxia, and die after 3-8 h of extreme
      hypoxia.

PMID- 28510785
TI  - The impact of leisure on mental health of Sardinian elderly from the 'blue zone':
      evidence for ageing well.
AB  - BACKGROUND: There has been scientific interest in the Sardinia population for a
      number of years and for a variety of reasons, including its extreme longevity.
      This is especially prevalent in the central-eastern region of the island, where a
      blue zone region has been precisely delineated. AIMS: The present study examines
      the influence of leisure activities on psychological well-being and depressive
      symptoms in elderly individuals living in the blue zone region of inner Sardinia.
      METHODS: Eighty-three participants were recruited according to strict inclusion
      criteria to ensure their cognitive and residency status. Individuals were
      assigned to either old (70-79 years) or very old (>=80 years) groups, and were
      administered a test battery to determine their socio-demographic and lifestyle
      characteristics, perceived physical health, and self-perceived well-being and
      depressive symptoms. RESULTS: The primary findings indicate that participation in
      leisure activities positively influenced both self-perceived well-being and
      depressive symptoms. There was though, a differential impact on different sub
      scales of well-being, and moreover, the overall pattern of results suggested
      primarily an influence on mood states and/or emotion regulation. CONCLUSIONS: The
      emerging psychological pattern of results about elders from the Sardinian blue
      zone region provides insight for the promotion of successful ageing in late
      adulthood.

PMID- 28510786
TI  - The impact of frailty on noninvasive mechanical ventilation in elderly medical
      intensive care unit patients.
AB  - AIM: Many factors affecting noninvasive ventilation (NIV) in critically ill
      patients have been reported in the literature, but there is no study about the
      effect of frailty. With this study, the frailty prevalence was evaluated with two
      different frailty scores among the NIV population of a medical intensive care
      unit (ICU). Besides, the impact of frailty on NIV success and mortality and its
      association with NIV application problems were evaluated. METHOD: A prospective
      observational cohort study was performed on patients who were over 50 years of
      age and assigned to NIV due to hypercapnic respiratory failure. For the
      assessment of frailty, Clinical Frailty Scale (CFS) and The Edmonton Frailty
      Scale (EFS) were used and the ones with CFS >=5 and EFS >=8 were considered as
      fragile. The study population was classified and compared according to NIV
      success, ICU outcome (discharge or exitus) and NIV application problems. RESULTS:
      A total of 103 patients with the mean age of 73 +/- 11 years were included. The
      incidence of frailty was 41% with CFS >=5 and 36% with EFS >=8. The NIV failure
      occurred in 30 (29%) patients. Among them frailty and SOFA score was higher;
      Glasgow Coma Scale (GCS) was lower. In multivariate analysis GCS (OR: 1.2, p:
      0.042) and frailty with EFS (OR: 2.8, p: 0.027) were identified as independent
      risk factors of NIV failure. Sixty-five (63%) patients had NIV application
      problems and frailty was higher among them with both CFS and EFS (p < 0.05).
      Mortality occurred in 18 (17%) patients; NIV failure and frailty according to CFS
      were independent risk factors of mortality. CONCLUSION: The frailty is associated
      with higher NIV application problems, failure and mortality risk in elderly ICU
      patients. The CFS and EFS frailty scores can be used to predict NIV success and
      outcomes in ICUs.

PMID- 28510788
TI  - Effects of volatile organic compound ether on cell responses and gene expressions
      in Arabidopsis.
AB  - BACKGROUND: The volatile organic compound ether is widely used as an industrial
      solvent and easily released to the environment. Our previous research indicated
      that ether triggers reactive oxygen species (ROS) production and activates
      ethylene biosynthetic genes and defense gene expressions in tomato. In the
      present study, we investigated the effect of ether on cell responses and gene
      expressions in Arabidopsis and compared the ROS and phytohormones produced in
      Arabidopsis and tomato plants in response to different air pollutants (O3 vs.
      ether). RESULTS: Ether induced the sequential production of superoxide anion and
      hydrogen peroxide in Arabidopsis. Ether also triggered expressions of ethylene,
      salicylic acid and jasmonic acid biosynthetic genes. The temporal expression
      patterns of MAP kinase and protein phosphatase genes are in good accordance with
      those of the ethylene and salicylic acid biosynthetic genes, suggesting that
      induction of these phytohormone biosynthesis were through signaling pathways
      including both phosphorylation and/or dephosphorylation. By contrast, expression
      pattern of protein phosphatase PP2A3&4 coincided well with the expression of
      jasmonic acid biosynthetic gene LOX4, suggesting that induction of jasmonic acid
      biosynthesis is through PP2A3&4. However, the production of ROS and temporal
      expression patterns of phytohormone biosynthetic genes in Arabidopsis in response
      to ether were different from those to O3 and were different from those in tomato
      as well. CONCLUSIONS: Different plants have different strategies to respond to
      the same abiotic stress, and each plant species possesses its own unique
      signaling pathways that regulate the responding process.

PMID- 28510787
TI  - A phase II trial of arsenic trioxide and temozolomide in combination with
      radiation therapy for patients with malignant gliomas.
AB  - Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic
      trioxide (ATO) is synergistic with RT based on several mechanisms of action
      previously identified, however not tested herein. The MTD of ATO, RT and TMZ was
      determined in a Phase I trial. We now present the combined Phase I/II data.
      Patients with newly diagnosed malignant gliomas were eligible for treatment.
      Patients were treated with RT (60 GY), TMZ (75 mg/m2 daily * 42 days) and ATO
      0.20 mg/kg daily in week 1 then twice a week *5 weeks, after completing RT they
      were treated with TMZ 5/28 for up to 12 months. MRIs were performed every 8
      weeks. A total of 42 patients were enrolled in both the Phase I and II trials for
      this study treatment. Of the 42 enrolled patients (24 M and 18 W) the median age
      was 54 (24-80) and median KPS 90 (60-100). 28 patients had a GBM and 14 had
      anaplastic glioma (AG). All patients completed RT/TMZ/ATO and went on to
      maintenance TMZ. Median number of post RT cycles of TMZ was 4 (0-12). Median PFS
      was 7 m for GBM and 75 m for AG and median OS was 17 m for GBM and NR for AG.
      Best response was CR in 2, SD in 28, PR in 5 and PD in 7. There were no
      unexpected adverse events. Grade 3 toxicities likely attributable to ATO included
      prolonged Qtc (n = 1), elevated liver enzymes (n = 2 for ALT/n = 1 for AST) and
      elevated bilirubin (n = 1). Adding ATO to RT and TMZ is feasible with no
      increased side effects. The addition of arsenic did not improve overall survival
      in the GBM patients as compared to historic data. MGMT status was analyzed in 20
      of the 42 patients where tissue was available for retrieval and MGMT testing.

PMID- 28510789
TI  - Pittosporum peridoticola (Pittosporaceae), a new ultramafic obligate species
      restricted to Kinabalu Park (Sabah, Malaysia).
AB  - BACKGROUND: Kinabalu Park, in Sabah (Malaysia) on Borneo Island, is renowned for
      the exceptionally high plant diversity it protects, with at least 5000 plant
      species enumerated to date. Discoveries of plant novelties continue to be made in
      Sabah, especially on isolated ultramafic outcrops, including in the genus
      Pittosporum (Pittosporaceae) with P. linearifolium from Bukit Hampuan on the
      southern border of the Park, and P. silamense from Bukit Silam in Eastern Sabah,
      both narrow endemics restricted to ultramafic soils. RESULTS: A distinctive new
      species of Pittosporum (P. peridoticola J.B.Sugau and Ent, sp. nov.) was
      discovered on Mount Tambuyukon in the north of Kinabalu Park during ecological
      fieldwork. The diagnostic morphological characters of this taxon are discussed
      and information about the habitat in which it grows is provided. The soil
      chemistry in the rooting zone of P. peridoticola has high magnesium to calcium
      quotients, high extractable nickel and manganese concentrations, but low
      potassium and phosphorus concentrations, as is typical for ultramafic soils.
      Analysis of foliar samples of various Pittosporum-species originating from
      ultramafic and non-ultramafic soils showed a comparable foliar elemental
      stoichiometry that is suggestive of 'Excluder-type' ecophysiology. CONCLUSION:
      Pittosporum peridoticola is an ultramafic obligate species restricted to Kinabalu
      Park with only two known populations within the boundaries of the protected area.
      It is vulnerable to any future stochastic landscape disturbance events, such as
      forest fires or severe droughts, and therefore its conservation status is 'Near
      Threatened'.

PMID- 28510791
TI  - Actephila alanbakeri (Phyllanthaceae): a new nickel hyperaccumulating plant
      species from localised ultramafic outcrops in Sabah (Malaysia).
AB  - The Malaysian state of Sabah on the Island of Borneo is emerging as a hotspot for
      nickel hyperaccumulator species with at least 25 such species discovered to date.
      New discoveries of the hyperaccumulation trait in described taxa, as well as
      taxonomical novelties that are nickel hyperaccumulators, continue to be made.
      Here we describe a new nickel hyperaccumulating species of Actephila
      (Phyllanthaceae) originating from two known populations on ultramafic soils in
      Sabah. The most characteristic feature of Actephila alanbakeri are its knobbly
      fruits, but other diagnostic morphological characters are discussed and
      information about its ecology and rhizosphere and plant tissue chemistry is
      provided. This new species is one of the strongest known nickel hyperaccumulator
      plants in Southeast Asia with up to 14,700 MUg g-1 (1.47 %) nickel in its leaves.
      The occurrences of Actephila alanbakeri on just two sites, both of which lie
      outside protected areas and are disturbed by recurring forest fires, combined
      with the small total numbers of individuals, render this species Endangered (EN)
      on the basis of IUCN Red List Criteria.

PMID- 28510790
TI  - Leaf senescence induced by EGY1 defection was partially restored by glucose in
      Arabidopsis thaliana.
AB  - BACKGROUND: Ethylene-dependent gravitropism-deficient and yellow-green 1 (EGY1)
      protein is required for chloroplast development and photosynthesis conduction.
      The egy1 deletion mutants have a yellow-green phenotype and reduced granal
      thylakoids. Furthermore, the yellow-green phenotype of egy1 mutants is more
      obvious than that of wild-type (WT) plants with increasing leaf age, suggesting
      an early senescence in the egy1 mutants. However, the relationship between EGY1
      functions and leaf senescence still remains poorly understood. RESULTS: We
      observed that egy1 mutant leaves were more yellow than those of WT (the same age)
      in Arabidopsis thaliana. In accompany with this phenotype, leaf survival,
      chlorophyll content, Fv/Fm and soluble protein content decreased, and ion leakage
      increased significantly in egy1 mutants compared to WT plants. At molecular
      level, the expressions of senescence-associated genes increased, and
      photosynthesis genes decreased significantly in the mutants compared to those in
      WT plants. Furthermore, after darkness treatment, the yellow-green phenotype of
      egy1 mutants was more obvious than that of WT. These results indicate that the
      loss-of-function of egy1 gene induces leaf senescence in A. thaliana. In
      addition, our results showed that the yellow-green phenotype, chlorophyll content
      and ion leakage of egy1 mutants was partially restored after exogenously applied
      glucose for 5 weeks. At the same time, the expression of hexokinase 1 (HXK1)
      and/or senescence-associated gene 12 (SAG12) in egy1 mutants growing on 2 %
      glucose was lower than that in egy1 mutants without glucose. CONCLUSION: EGY1
      defection induced leaf senescence and this senescence was partially restored by
      glucose in A. thaliana.

PMID- 28510792
TI  - A Systematic Review of Proinsulin-Secreting Pancreatic Neuroendocrine Tumors.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of
      islet cell-derived neoplasms with a propensity toward hormone production. Among
      PNETs, proinsulin-secreting tumors (proinsulinomas) are exceedingly rare. The
      objective of this study is to collect and summarize the existing literature to
      provide a comprehensive evaluation of this uncommon disease. METHODS: A
      systematic review was performed to characterize the clinicopathologic features of
      proinsulinoma. Using the electronic biomedical databases PubMed, Ovid Medline,
      and Embase, 316 publications were screened for relevance of which 14 were
      selected. We also present two patients with proinsulinoma treated at Yale New
      Haven Hospital. RESULTS: Of the 16 patients included in the study, the mean age
      was 56.8 and there was a 2:1 female predominance. The majority of patients
      presented with symptomatic hypoglycemia with normal or low insulin levels. Median
      tumor diameter was 1.2 cm and 80% were located in the body and tail of the
      pancreas. Following resection, most patients had normalization of hormonal levels
      without recurrence (75%; 12/16). CONCLUSION: Proinsulinomas are rare pancreatic
      neuroendocrine tumors that have the potential to cause hypoglycemia. While
      insulinomas and proinsulin-secreting tumors have many physiologic parallels,
      these cases illustrate several key distinctions in their diagnosis and
      management.

PMID- 28510793
TI  - Cholecystectomy Following Idiopathic Pancreatitis: How Much to Look for Stones? :
      Correspondence re Stevens, et al.: How Does Cholecystectomy Influence Recurrence
      of Idiopathic Acute Pancreatitis? J Gastrointest Surg (2016) 20:1997-2001.

PMID- 28510796
TI  - Focus on Bio-Ion Chemistry: Interactions of Biological Ions with Ions, Molecules,
      Surfaces, Electrons, and Light, Honoring Scott A. McLuckey, Recipient of the 2016
      ASMS Award for a Distinguished Contribution in Mass Spectrometry.

PMID- 28510794
TI  - Long-Term Trends in Hematological and Nutritional Status After Gastrectomy for
      Gastric Cancer.
AB  - BACKGROUND: This study investigated long-term trends in hematological and
      nutritional parameters after gastrectomy for gastric cancer and evaluated the
      influence of the reconstruction type on these trends. METHODS: The medical
      records of 558 patients who underwent curative gastrectomy with standard lymph
      node dissection for stage I gastric cancer between January 2006 and December 2013
      were reviewed. The hematological and nutritional parameters evaluated included
      hemoglobin, ferritin, vitamin B12, total protein, albumin, total cholesterol,
      triglyceride, and calcium. The patients were followed up for 6 months
      postoperatively and then annually until death, cancer recurrence, or follow-up
      loss. RESULTS: In the long term, ferritin and triglyceride gradually decreased
      after gastrectomy, while the other parameters decreased slightly or were stable.
      In the comparisons according to reconstruction type, the Roux-en-Y group had the
      lowest levels of hemoglobin, ferritin, vitamin B12, total protein, albumin, and
      total cholesterol beginning 6 months postoperatively compared with the Billroth I
      and II groups. However, only ferritin and vitamin B12 had significant differences
      in the 5-year cumulative incidences of deficiency/reduction according to the
      reconstruction type, whereas albumin, triglyceride, total cholesterol, and
      calcium did not. CONCLUSIONS: Although malabsorption and malnutrition are common
      in patients after a gastrectomy, most nutritional parameters were stable or
      decreased slightly in the long-term and were not markedly influenced by the
      reconstruction type or extent of gastrectomy. Therefore, for more accurate
      nutritional assessment after gastrectomy, multidirectional monitoring should be
      considered rather than simply measuring biochemical parameters.

PMID- 28510795
TI  - Liver Stiffness Assessed by Shear Wave Elastography Predicts Postoperative Liver
      Failure in Patients with Hepatocellular Carcinoma.
AB  - BACKGROUND: Cirrhosis increases a patient's risk of developing postoperative
      liver failure (PLF). Liver stiffness (LS), assessed by two-dimensional shear wave
      elastography (SWE), indicates liver fibrosis with high accuracy. Whether LS is
      superior to portal hypertension (PHT) in predicting PLF remains to be studied.
      METHODS: The study enrolled 280 patients who underwent hepatectomy for
      hepatocellular carcinoma from July 2015 to July 2016. All patients received
      preoperative assessments for LS, PHT, and serum markers of liver fibrosis in
      addition to other clinicopathological tests. Risk factors for grade A and grade B
      (or greater) PLF were subjected to univariate and multivariate analysis and
      receiver operating characteristic curve analysis. RESULTS: Fifty-five patients
      (19.6%) experienced PLF. The cutoff value of LS for predicting cirrhosis was 10.1
      kPa. Multivariate analysis identified LS, hyaluronic acid, IV collagen, and the
      presence of splenomegaly as independent predictors of PLF. The cutoff value of LS
      for predicting PLF and grade B (or greater) PLF was 11.75 and 11.9 kPa,
      respectively. LS was superior to PHT in predicting PLF or greater than grade B
      PLF (0.72 vs. 0.60, 0.76 vs. 0.59, P < 0.05). CONCLUSION: LS measured by SWE can
      predict risk of PLF with greater accuracy than PHT.

PMID- 28510797
TI  - Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3
      Glucuronide, and Morphine-6-Glucuronide.
AB  - INTRODUCTION: Obesity is associated with many pathophysiological changes that may
      result in altered drug metabolism. The aim of this study is to investigate the
      influence of obesity on the pharmacokinetics of morphine, morphine-3-glucuronide
      (M3G), and morphine-6-glucuronide (M6G) through a combined analysis in morbidly
      obese patients and non-obese healthy volunteers. METHODS: In this analysis, data
      from 20 morbidly obese patients [mean body mass index 49.9 kg/m2 (range 37.6-78.6
      kg/m2) and weight 151.3 kg (range 112-251.9 kg)] and 20 healthy volunteers [mean
      weight 70.6 kg (range 58-85 kg)] were included. Morbidly obese patients received
      10 mg of intravenous (I.V.) morphine after gastric bypass surgery, with
      additional morphine I.V. doses as needed. Healthy volunteers received an I.V.
      bolus of morphine of 0.1 mg/kg followed by an infusion of 0.030 mg kg-1 h-1 for 1
      h. Population pharmacokinetic modeling was performed using NONMEM 7.2. RESULTS:
      In morbidly obese patients, elimination clearance of M3G and M6G was decreased
      substantially compared with healthy volunteers (p < 0.001). Regarding
      glucuronidation, only a slight decrease in the formation of M6G and a delay in
      the formation of M3G was found (both p < 0.001). Obesity was also identified as a
      covariate for the peripheral volume of distribution of morphine (p < 0.001).
      CONCLUSION: Metabolism of morphine is not altered in morbidly obese patients.
      However, decreased elimination of both M3G and M6G is evident, resulting in a
      substantial increase in exposure to these two metabolites. A rational explanation
      of this finding is that it results from alterations in membrane transporter
      function and/or expression in the liver. ClinicalTrials.gov identifier:
      NCT01097148.

PMID- 28510798
TI  - Total Laparoscopic Management for Stage IV Colorectal Cancer Requiring
      Multivisceral Resection.
AB  - BACKGROUND: Surgical resection of all sites of disease, in combination with
      effective systemic chemotherapy, offers the only potential chance for cure for
      patients with stage IV colorectal cancer (CRC). Coordinated multistage resection
      using a minimally invasive approach may provide optimal oncologic outcome while
      potentially offering the benefit of decreased morbidity. PATIENT: A 66-year-old
      women presented with transverse colon cancer and synchronous metastasis (CRLM) in
      segment IV involving the middle hepatic vein and main left portal pedicle, as
      well as the left adrenal gland. Due to favorable response to neoadjuvant
      chemotherapy (FOLFOX/bevacizumab), the patient was considered for resection but
      developed some obstructive symptoms from the primary tumor, necessitating re
      coordination of treatment sequencing from the 'liver-first' approach. METHODS:
      The first procedure combined laparoscopic subtotal colectomy (extracorporeal
      anastomosis) with left adrenalectomy. After restaging, CRLM was removed
      separately 2 months later via laparoscopic left hepatectomy extending beyond the
      middle hepatic vein. Successful completion of the two procedures depended on
      optimal patient/port positioning for the combined colon/adrenal surgery and the
      second-stage liver resection. Postoperative lengths of stay were 4 and 3 days,
      respectively, and were without complication. Adjuvant FOLFOX was initiated 21
      days following liver surgery, and the patient has been disease-free for 36
      months. CONCLUSION: This case illustrates the feasibility of the total
      laparoscopic approach to multivisceral resection for synchronous stage IV CRC in
      the context of a preplanned, staged multidisciplinary strategy. This approach may
      offer optimal cancer management, including early return to systemic therapy,
      shortened time intervals between stages, and minimal postoperative morbidity.1 -
      3.

PMID- 28510799
TI  - Practical Surgical Techniques for Lymphadenectomy Along the Right Recurrent
      Laryngeal Nerve During Thoracoscopic Esophagectomy in the Prone Position.
AB  - BACKGROUND: In esophageal squamous cell cancer (SCC), lymphadenectomy along the
      right recurrent laryngeal nerve (RLN) is important for disease control. The
      metastatic rate was 33% and the 5-year overall survival rate of these patients
      was 33.3%,1 but the risk of RLN palsy increases.2 We reported a reliable new
      method ('Pincers Maneuver')3 for lymphadenectomy along the right RLN during
      thoracoscopic esophagectomy in the prone position (TEP), and hereby present our
      video, aimed at providing a complete and safe dissection. METHOD: The 'Pincers
      Maneuver' is performed for all resectable clinical stage IA-III lower, middle, or
      upper thoracic esophageal SCCs. Patients above clinical stage IB were treated
      with neoadjuvant chemotherapy. The concept of this procedure is to first
      exfoliate the two-dimensional membrane (lateral pedicle), which includes the
      right RLN, lymph nodes, and the primary esophageal artery, from the right side of
      the trachea toward the neck. Improved mobility of the lateral pedicle, gained by
      closing in from its inner and outer sides, enables easy lymphadenectomy along the
      right RLN toward the right inferior thyroid artery. RESULTS: Using this method,
      we performed 31 TEPs in 2016 at Kobe University Hospital. Median body mass index
      was 23 kg/m2 (range 18-31). No right RLN palsy greater than Clavien-Dindo
      classification grade I was observed. On average, 5.2 +/- 2.7 nodes were harvested
      along the right RLN, with a 23% metastatic rate. CONCLUSIONS: Our method for
      lymphadenectomy along the right RLN during TEP is safe and practical. It provides
      sufficient lymph node dissection, and no right RLN palsy has been observed.

PMID- 28510800
TI  - Structural modulation of gut microbiota in Bama minipigs in response to treatment
      with a "growth-promoting agent", salbutamol.
AB  - Even though salbutamol (SAL) had remarkable effects on the enhancement of growth
      rate and carcass composition in different livestock species such as cattle, pigs,
      sheep and poultry, it was banned as a growth promoter because of its adverse
      effects on health. However, the specific mechanism by which salbutamol enhances
      growth efficiency remains unknown. In this study, Bama pigs were randomly
      allocated to receive salbutamol (5 mg/kg) for 30 or 60 days and were compared
      with untreated pigs. Pigs treated with salbutamol demonstrated enhanced growth
      rates and carcass composition; however, they showed deterioration in blood
      biochemical indices and organ development. We hypothesized that salbutamol exerts
      its effects by modulating the composition of the gut microbiota population. The
      faecal microbiome of pigs was characterized via pyrosequencing of the bacterial
      16S rRNA gene. The gut microbiota population analysis showed that salbutamol
      caused shifts in the microbial composition of less abundant species. Redundancy
      analysis indicated an increase in abundance of the phylum Bacteroidetes, class
      Betaproteobacteria, family Christensenellaceae and genus Lactobacillus, and a
      decreased ratio of the phylum Firmicutes, class Clostridia and genera
      Ruminococcus, Blautia and Subdoligranulum. In conclusion, our study provided
      circumstantial evidence that the various effects of salbutamol are caused by gut
      microbiota modulation, and several potential candidates were identified for SAL
      detection via the gut microbiota. Our findings provided new insights into the
      roles of the gut microbiota during salbutamol treatment, and these findings will
      aid in the screening of alternative strategies for animal health improvement and
      production enhancement.

PMID- 28510801
TI  - Characterization of an autotrophic bioreactor microbial consortium degrading
      thiocyanate.
AB  - Thiocyanate (SCN-) forms as a by-product of cyanidation during gold ore
      processing and can be degraded by a variety of microorganisms utilizing it as an
      energy, nitrogen, sulphur and/or carbon source. In complex consortia inhabiting
      bioreactor systems, a range of metabolisms are sustained by SCN- degradation;
      however, despite the addition or presence of labile carbon sources in most
      bioreactor designs to date, autotrophic bacteria have been found to dominate key
      metabolic functions. In this study, we cultured an autotrophic SCN--degrading
      consortium directly from gold mine tailings. In a batch-mode bioreactor
      experiment, this consortium degraded 22 mM SCN-, accumulating ammonium (NH4+) and
      sulphate (SO42-) as the major end products. The consortium consisted of a diverse
      microbial community comprised of chemolithoautotrophic members, and despite the
      absence of an added organic carbon substrate, a significant population of
      heterotrophic bacteria. The role of eukaryotes in bioreactor systems is often
      poorly understood; however, we found their 18S rRNA genes to be most closely
      related to sequences from bacterivorous Amoebozoa. Through combined chemical and
      phylogenetic analyses, we were able to infer roles for key microbial consortium
      members during SCN- biodegradation. This study provides a basis for understanding
      the behaviour of a SCN- degrading bioreactor under autotrophic conditions, an
      anticipated approach to remediating SCN- at contemporary gold mines.

PMID- 28510802
TI  - Phase I/II study of bi-weekly XELIRI plus bevacizumab treatment in patients with
      metastatic colorectal cancer resistant to oxaliplatin-based first-line
      chemotherapy.
AB  - PURPOSE: We aimed to determine the recommended dose for bi-weekly XELIRI plus
      bevacizumab for second-line chemotherapy and examined its safety and efficacy in
      patients with metastatic colorectal cancer resistant to oxaliplatin-based first
      line chemotherapy. METHODS: Irinotecan and bevacizumab were administered as a
      continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively.
      Capecitabine was orally administered in two divided doses on Days 2-8. Each 2
      week treatment cycle was defined as a single course of treatment. During Phase I,
      we determined the recommended dose for capecitabine. In Phase II trials, efficacy
      and treatment safety was verified (UMIN000003934). RESULTS: The recommended dose
      of capecitabine was determined to be 2000 mg/m2. Median progression-free survival
      was 7.8 months [95% confidence interval (CI) 6.1-10.9 months], and median overall
      survival was 18.9 months (95% CI 11.6-28.4 months). Response rate was 17.4% (95%
      CI 6.4-28.3%). The most common Grade >=3 hematotoxic adverse events were anemia
      (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of
      Grade >=3 non-hematotoxic adverse events was relatively low (<10%). CONCLUSION:
      Bi-weekly XELIRI plus bevacizumab was found to be a safe and effective second
      line treatment in patients with metastatic colorectal cancer resistant to
      oxaliplatin-based first-line chemotherapy.

PMID- 28510804
TI  - Broadening the Lens of System-Based Practice: From Micro to Macro and Basic to
      Complex in Residency Training.
AB  - OBJECTIVE: This paper aimed to develop a model for understanding the various
      dimensions of system-based practice (SBP) and determine the extent to which
      psychiatry residents perform behaviors along these dimensions. METHODS: Sixty-one
      supervisors from seven psychiatry programs rated resident performance of SBP
      behaviors using a 60-item instrument. Multi-dimensional scaling and cluster
      analysis were conducted to determine how the instrument items related to one
      another and the larger concept of SBP. Average supervisor ratings between
      clusters were compared to determine resident performance along the identified SBP
      dimensions. RESULTS: The data supports a model of SBP defined along two
      dimensions: (1) from micro (patient) to macro (population-based) interventions
      and (2) from low to high system complexity. Residents were more likely to perform
      behaviors at the patient level compared to those at the population-based level.
      CONCLUSIONS: Training in SBP remains predominately focused on the doctor-patient
      level and not the greater system of health-care delivery.

PMID- 28510803
TI  - Occupational and life-style factors-acquired mutagenicity in agric-workers of
      northeastern Brazil.
AB  - Pesticides are a complex mixture of chemicals used to protect crops from a number
      of pests and diseases. They have been considered as potential mutagenic agents.
      This study aims at evaluation of the mutagenic effect of pesticide exposure to
      agricultural workers through chromosomal aberrations (CA) and micronucleus (MN)
      assay in peripheral blood lymphocytes and oral mucosal cells, respectively. The
      exposed group was consisted with 97 farmers, while the control (un-exposed) group
      consisted of 55. The results showed a significant (p < 0.05) increase in
      frequency of CA and MN in the exposed group. Both CA and MN profiles were linked
      to a significant (p < 0.05) co-relation with the confounding factors such as
      smoking habits, alcohol, vegetables, tea/coffee, vitamins, and sweetener
      consumptions. More cytogenetic events were denoted in smoking and alcohol
      consumption as well as non-personal protective equipment (non-PPE) and low/no
      vegetables user farmers. In conclusion, a deficiency of dietary and medicaments
      derived antioxidants, while consumption of alcohol and tobacco, as well as
      effects of radiation, heavy metal poisoning (especially from sweeteners), and non
      PPE using habits, may contribute cytogenetic damage to the workers.

PMID- 28510805
TI  - Interventional radiology in iatrogenic ureteral leaks: case series and literature
      review.
AB  - Iatrogenic ureteral injuries are a dramatic complication in medical practice.
      Nowadays there are no universal guidelines for their management. The aim of our
      study was to evaluate the feasibility of the percutaneous treatment in restoring
      ureteral integrity in 19 patients that came to our attention. In each case
      retrograde stenting failed and patients were candidates for re-surgery. Our
      strategy consists of two phases. The first step is the nephrostomy that allows an
      external urinary diversion putting dry the damaged ureteral segment. The second
      step is the anterograde ureteral double-J stenting that keeps near the two stumps
      promoting the healing of the injured tract. In complete sections, when both
      retrograde and anterograde stenting singularly failed, we performed a rendez-vous
      technique with a combined radiological trans-nephrostomic access and urological
      cystoscopic approach to realign and catheterize the ureteral stumps. In patients
      with Bricker urinary diversion, peri-anastomotic leaks were treated by
      positioning a multi-hole pig-tail catheter with the inner end in the renal pelvis
      and the distal portion outgoing from the cutaneous stoma. Subsequent pyelographic
      controls demonstrated the resolution of the ureteral leak in all patients and
      none required a surgical re-intervention. Nephrostomies were removed and ureteral
      stents were regularly changed. We conclude that interventional uro-radiology may
      offer a valid conservative option in iatrogenic urinary injuries.

PMID- 28510806
TI  - Role of core needle biopsy in primary breast lymphoma.
AB  - Primary breast lymphoma (PBL) may mimic carcinoma clinically and also
      mammographic and ecographic distinction is subtle. Despite its rarity, incidence
      of PBLs has increased over the last four decades and continues to increase for
      younger women and for some subtypes, and for this reason it is increasingly
      important to achieve a preoperative pathological diagnosis using core needle
      biopsy (CNB) or fine-needle aspiration cytology (FNA). The aim of this
      retrospective study was to report our single-center experience in CNBs performed
      for histological diagnosis of PBL compared to FNA. From a total of 10,500 CNBs we
      found seven patients affected by PBL diagnosed at Careggi Florence University
      Hospital, between January 2000 and December 2016. Diffuse large B cell lymphoma
      (DLBCL) was the most frequent PBLs and on CNBs specimens was possible do the
      fluorescent in situ hybridization analysis to evaluate the presence of
      chromosomal translocation. CNB is an effective method for the assessment of PBLs,
      especially for DLBCL, in which a correct and fast classification could change the
      therapeutic approach and the prognosis.

PMID- 28510807
TI  - Incidence of hepatic encephalopathy after transjugular intrahepatic portosystemic
      shunt (TIPS) according to its severity and temporal grading classification.
AB  - OBJECTIVES: To evaluate hepatic encephalopathy (HE) incidence after transjugular
      intrahepatic portosystemic shunt (TIPS) and classify by gravity and frequency.
      METHODS: This is a retrospective study of 75 patients with no previous episodes
      of HE who underwent TIPS between 2008 and 2014 with clinical follow-up after 6
      and 12 months. Patient risk factors evaluated include age, INR (international
      normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage
      Liver Disease). HE was reported using two classifications: (1) gravity divided in
      moderate (West-Haven grades I-II) and severe (III-IV); (2) frequency divided in
      episodic and recurrent/persistent. RESULTS: Overall HE incidence was 36% at 6
      months, with 12 month incidence significantly decreased to 27% (p = 0.02). 13/75
      (17%) patients had one episode of moderate HE, while 3/75 (4%) patients had
      severe recurrent/persistent HE. Age was the only pre-TIPS risk predictor. Post
      TIPS bilirubin and INR showed variations from basal values only in the presence
      of diagnosed HE. Bilirubin significantly increased (p = 0.03) in correlation to
      HE severity, whereas INR changes correlated with temporal frequency (p = 0.04).
      HE distribution classified for severity is similar at 6 and 12 months, whereas
      when classified for frequency shows significant differences (p = 0.04).
      CONCLUSIONS: A classification by gravity and frequency attests post-TIPS HE as a
      manageable risk. Monitoring of bilirubin and INR may help on clinical management
      risk stratification.

PMID- 28510809
TI  - Transcatheter arterial embolization for intercostal arterio-esophageal fistula in
      esophageal cancer.
AB  - BACKGROUND: While esophageal fistula formation in the adjacent organs is
      associated with high rates of morbidity and mortality, the management of non
      aortic arterio-esophageal fistula has not been frequently reported. CASE
      PRESENTATION: A 69-year-old Japanese man who had undergone definitive
      chemoradiotherapy for esophageal cancer was admitted to our hospital with
      hematemesis. He was diagnosed with mediastinal abscess caused by esophageal
      perforation, and esophageal bypass surgery was performed. After 3 days, he
      presented with fatal hemoptysis. As angiography revealed an intercostal artery
      pseudoaneurysm, transcatheter arterial embolization was performed. CONCLUSIONS:
      When patients with esophageal cancer, especially those with a history of
      radiotherapy and/or mediastinitis, present with hematemesis and/or hemoptysis,
      the possibility of non-aortic arterio-esophageal fistula should be considered.
      Transcatheter arterial embolization is an effective treatment for non-aortic
      arterio-esophageal fistula.

PMID- 28510808
TI  - Development of a contouring guide in three different head set-ups for hippocampal
      sparing radiotherapy: a practical approach.
AB  - BACKGROUNDS: Irradiation of the hippocampus plays a role in neurocognitive
      toxicity. Its delineation is complex and in practice different head position can
      vary hippocampus morphology on axial images; so atlas in a single standard
      position can result ineffective to describe different hippocampal morphologies in
      different head set-up. The purpose of our study was to develop a guide based on
      magnetic resonance imaging for hippocampus delineation in three different head
      set-ups. MATERIALS AND METHODS: Three patients were selected to elaborate our
      guide. Patients were submitted to a planning computed tomography of the brain
      district in different head positions: 1 degrees  patient in neutral, 2 degrees 
      patient in over-extended and 3 degrees  patient in head hypo-extended position;
      axial images of 2-mm thickness were obtained. Computed tomography images were
      fused with diagnostic brain magnetic resonance images; then hippocampus was
      delineated according to RTOG atlas. Contours were revised by two neuro
      radiologists with >5-year expertise in neuroimaging. RESULTS: A guide was
      developed for each of three head positions considered. RTOG atlas provided an
      easy and reliable guide for hippocampus delineation in neutral position of the
      head. Discrepancies were observed in cranial and caudal limit in case of head
      over/hypo-extension, as well as in hippocampal morphology near the encephalic
      trunk where hippocampus takes an oblong shape in over-extended set-up, and short
      and stocky in hypo-extension. CONCLUSION: Our guide can represent a useful tool
      for hippocampal delineation in clinical practice and for different anatomic
      variations due to different head positions. Certainly, it should be validated in
      practice.

PMID- 28510810
TI  - Philodendron luisae (Araceae), a new species from Rio de Janeiro State, Brazil.
AB  - BACKGROUND: Philodendron is the second largest genus of Araceae, being highly
      diverse in the Atlantic Forest biome, with nearly one third of the Brazilian
      species occurring in Southern Brazil, particularly in Rio de Janeiro state.
      During a local inventory in Silva Jardim municipality, we found a peculiar
      population of Philodendron growing in lowland rainforest. RESULTS: After
      morphological analysis and comparisons with similar species, the population
      proved to be a new undescribed species of subgenus Philodendron section
      Macrobelium. CONCLUSIONS: The new species, named Philodendron luisae, is here
      described, illustrated and compared to morphologically close species.

PMID- 28510811
TI  - Study on the effect of magnetic field treatment of newly isolated Paenibacillus
      sp.
AB  - BACKGROUND: Symbiotic nitrogen fixation in plants occurs in roots with the help
      of some bacteria which help in soil nitrogen fertility management. Isolation of
      significant environment friendly bacteria for nitrogen fixation is very important
      to enhance yield in plants. RESULTS: In this study effect of different magnetic
      field intensity and treatment time was studied on the morphology, physiology and
      nitrogen fixing capacity of newly isolated Paenibaccilus sp. from brown soil. The
      bacterium was identified by 16S rDNA sequence having highest similarity (99%)
      with Paenibacillus sp as revealed by BLAST. Different magnetic intensities such
      as 100mT, 300mT and 500mT were applied with processing time of 0, 5, 10, 20 and
      30 minutes. Of all these treatment 300mT with processing time of 10 minutes was
      found to be most suitable treatment. Results revealed that magnetic treatment
      improve the growth rate with shorter generation time leading to increased enzyme
      activities (catalase, peroxidase and superoxide dismutase) and nitrogen fixing
      efficiencies. High magnetic field intensity (500mT) caused ruptured cell
      morphology and decreased enzyme activities which lead to less nitrogen fixation.
      CONCLUSION: It is concluded that appropriate magnetic field intensity and
      treatment time play a vital role in the growth of soil bacteria which increases
      the nitrogen fixing ability which affects the yield of plant. These results were
      very helpful in future breading programs to enhance the yield of soybean.

PMID- 28510812
TI  - Nostoc sp. extract induces oxidative stress-mediated root cell destruction in
      Mimosa pigra L.
AB  - BACKGROUND: Mimosa pigra is an invasive weed in some regions of South East Asia
      and Australia. Our previous study has revealed that a cyanobacterium, Nostoc sp.,
      extract can inhibit root growth in M. pigra seedlings. In this study, some
      physiological processes involve oxidative stress-mediated cell death and root
      ultrastructure were investigated to clarify the mechanisms of root growth
      suppression and bioherbicidal potential of the extract. RESULTS: Nostoc sp.
      extract enhanced overproduction of reactive oxygen species (ROS) at 24 h, the
      intensity of red fluorescence increased at 72 h, and caused a slightly increased
      H2O2 consistent with the activation of scavenging enzymes (catalase, ascorbic
      acid peroxidase, glutathione reductase, and peroxidases). This suggests that
      oxidative stress occurred in the presence of the extract which was supported by
      increased cell death and lipid peroxidation at 24 h. Reduction of malondialdehyde
      content and an increase in cell death at 72 h indicated oxidative damage and
      cellular leakage. Ultrastructural changes were determined at 72 h by scanning
      electron micrographs which confirmed the damage of epidermal and root cap cells
      and the disaggregation and destruction of root tip cells. Transmission electron
      micrographs showed the dissolution of the middle lamella, deposition of some
      substances in vacuoles, and abnormal mitochondria (swollen mitochondria and
      indistinct cristae). CONCLUSIONS: Nostoc sp. extract enhance oxidative stress by
      ROS production resulting in lipid peroxidation and massive cell death despite the
      activation of antioxidative enzymes. Understanding mechanism of action of Nostoc
      sp. extract will provide information for application of the extract to use as
      natural herbicide for control of M. pigra.

PMID- 28510813
TI  - Effects of yam dioscorin interventions on improvements of the metabolic syndrome
      in high-fat diet-induced obese rats.
AB  - BACKGROUND: The metabolic syndrome (MS) is termed a cluster of multiple metabolic
      risk criteria which is positively correlated with cardiovascular disease and type
      2 diabetes mellitus (DM). Yam dioscorins have been reported to exhibit biological
      activities, however, little is known their preventive effects on the MS.
      Therefore, a high-fat (HF) diet was used to induce Wistar rat obesity and then
      yam dioscorin (50 mg/kg, dio50) was intervened daily concurrent HF diet (HF diet
      + dio50) for five weeks to check the changes of weights of body and tissues,
      blood pressures, and impaired glucose tolerances. The in vitro peptic
      hydrolysates of dioscorin with molecular mass between 3 kDa and 10 kDa and less
      than 3 kDa were used to determine dipeptidyl peptidase IV (DPP IV) inhibitory
      activities which DPP IV inhibitor has been reported to prevent and treat type 2
      DM. RESULTS: There were no significant difference in body weights, feed intakes,
      feed conversion, and weights of adipose tissues of obese rats in groups of HF and
      (HF diet + dio50). However, the systolic blood pressures in obese rats of 2-, 3-
      and 4-week dioscorin interventions were showed significantly lower (P < 0.05)
      compared to the HF group. The dioscorin intervention (HF+ dio50) was showed
      significantly different (P < 0.05) and improved the impaired glucose tolerances
      compared to HF group in obese rats by the oral glucose tolerance tests. It was
      also found that the fraction with different molecular mass of dioscorin peptic
      hydrolysates (5 mg/ml) showed inhibitory activities against DPP IV using
      sitagliptin phosphate as positive controls. CONCLUSIONS: Yam dioscorins exhibit
      improved MS activities in obese rats which the related mechanisms may need
      further investigations.

PMID- 28510814
TI  - The endophytic fungi of Salvia miltiorrhiza Bge.f. alba are a potential source of
      natural antioxidants.
AB  - BACKGROUND: Salvia miltiorrhiza Bge. f. alba is a traditional Chinese herbal drug
      with special pharmacological effect on thromboangiitis obliterans. However, the
      nature source of S.miltiorrhiza Bge.f.alba is now in short supply because of the
      over-collection of the wild plant. To better utilize this resource, the diversity
      and antioxidant activity of endophytic fungi isolated from S. miltiorrhiza Bge.
      f. alba were investigated. RESULTS: A total of 14 endophytic fungi were isolated
      from different parts of S. miltiorrhiza Bge.f.alba. Based on morphological and
      molecular identification, the endophytic fungi isolated were classified into four
      genera (Alternaria sp., Fusarium sp., Schizophyllum sp. and Trametes sp.). These
      fungal extracts were prepared using ethanol and evaluated for their phytochemical
      compounds and antioxidant activity. Alternaria alternata SaF-2 and Fusarium
      proliferatum SaR-2 are of particular interest because they yielded all of nine
      phytochemicals including saponins, phenol, flavonoids, cardiac glycosides,
      steroids, tannins, alkaloids, anthroquinone and terpenoids. F. proliferatum SaR-2
      and A. alternata SaF-2 also exhibited stronger antioxidant activities by FRAP and
      DPPH method, having the higher levels of phenol and flavonoid than those of plant
      root. The total amount of phenol and flavonoid quantified were of 21.75, 20.53
      gallic acid equivalent per gram and 8.27 and 7.36 MUg/mg of quercetin equivalent
      respectively. These two endophytic fungi (SaR-2 and SaF-2) were found to have
      comparable scavenging abilities on both FRAP (1682.21 and 1659.05 MUmol/mg,
      respectively) and DPPH-free radicals (90.14% and 83.25%, respectively, at 0.1
      mg/mL). This is the first report about isolation of endophytic fungi from S.
      miltiorrhiza Bge.f.alba and their antioxidant activities. CONCLUSIONS: These
      results indicate that the endophytic fungi associated with S. miltiorrhiza Bge.f.
      alba can be a potential source of novel natural antioxidants.

PMID- 28510815
TI  - Lipid accumulation in response to nitrogen limitation and variation of
      temperature in Nannochloropsis salina.
AB  - BACKGROUND: This batch study deals with the relation between lipid as well as
      triglyceride contents in Nannochloropsis salina and variation in culture
      conditions such as nitrogen concentration and temperature. RESULTS: The tested
      parameters caused reduction in growth expressed as cell count, optical density
      and dry weight, as well strongly involved in lipids and triglycerides
      accumulation and significantly affected the lipid productivity. At the beginning
      of the work, the concentration of nitrogen in the medium was reduced to three
      quarter, half and quarter of the original f2 medium while the temperature kept
      constant. After that, the optimal nitrogen concentration (quarter of the original
      media) giving high lipid yield was tested with different temperature degrees from
      15 to 35 degrees C with five degree intervals. Although the growth was
      insignificantly influenced, a considerable increase in lipid and triglyceride
      (56.1 and 15.1% of dry weight respectively) was observed when the concentration
      of nitrogen in the medium was reduced to the quarter. Moreover, 59.3% lipid and
      17.1% triglyceride on the basis of dry weight were obtained by the combination of
      25% nitrogen concentration and 30 degrees C. Simple regressions recommended that
      the interaction effect of nitrogen limitation and temperature on lipid and
      triglyceride accumulation was not as fundamental as for nitrogen limitation
      stress. CONCLUSION: The degree of nitrogen availability in the combination of
      temperature effect has been identified as the critical determinant for the
      maximal production of lipid in N. salina. Nevertheless, major advances in this
      field can be considered by studying more stresses techniques and genetic
      strategies.

PMID- 28510816
TI  - Two new species of Begonia, B. moneta and B. peridoticola (Begoniaceae) from
      Sabah, Malaysia.
AB  - BACKGROUND: Mount Kinabalu, reknowned for its high biodiversity and endemism, is
      a National Park in the State of Sabah on the northern end of the island of
      Borneo. Every year many visit the higher part of the Kinabalu National Park,
      while most lowland forests in the Park are under-explored. Two unknown species of
      Begonia were collected from a peridotic (ultramafic) cliff in the Kinabalu
      National Park at ca. 400 m elevation. RESULTS: The two species are named B.
      moneta C.-I Peng, Rimi & C. W. Lin and B. peridoticola Rimi, C.-I Peng & C. W.
      Lin. Begonia moneta (sect. Baryandra) is similar to B. gueritziana Gibbs, a
      widespread species of the same section in Borneo, differing in the peltate (vs.
      basifixed) leaves and the smaller flower parts. Also, their chromosome numbers
      are different (B. moneta, 2n = 30; B. gueritziana, 2n = 28). The peltate and
      succulent foliage of B. moneta is also reminiscent of B. burttii Kiew & S. Julia
      and B. payung S. Julia & Kiew, both of sect. Reichenheimia, from Sarawak. Begonia
      moneta is distinct from the two species in having branched (vs. entire) placental
      lamellae. Additionally, B. moneta differs from B. burttii in having 4 (vs. 5)
      tepals in pistillate flowers and markedly unequal (vs. equal) fruit wings.
      Begonia moneta differs from B. payung in the smaller leaves and conspicuously
      winged (vs. wingless) capsules. Begonia peridoticola (sect. Petermannia)
      resembles B. punchak Kiew & S. Julia from limestone areas in Kuching Division,
      Sarawak, differing in the entire leaf margin (vs. distantly dentate), much larger
      capsular wings (8-11 mm vs. 2-3 mm wide) and yellow, spiral (vs. crimson, U
      shaped) styles. CONCLUSION: A careful study of the herbarium materials and
      literature supports the recognition of the two new species. Detailed
      descriptions, line drawings, color plates, chromsome data, foliar SEM
      observations and comparisons with phenetically similar species are provided to
      aid in identification.

PMID- 28510818
TI  - Six new species of Begonia (Begoniaceae) from limestone areas in Northern
      Vietnam.
AB  - BACKGROUND: Species of Begonia are richly represented in limestone karst areas
      across the Sino-Vietnamese border. More than one hundred species were known, many
      of which were documented recently. RESULTS: In continuation of our systematic
      studies of Asian Begonia, we report six species of Begonia that are unknown to
      science, namely B. caobangensis [sect. Platycentrum], B. circularis, B.
      melanobullata, B. langsonensis, B.locii and B. montaniformis [sect. Coelocentrum]
      from Northern Vietnam. Diagnostic features that separate them from
      morphologically allied species are provided. Somatic chromosome numbers were
      determined, which supports their placement in the respective sections. Foliar SEM
      microphotographs were taken and described. CONCLUSION: A careful study of the
      literature, herbarium specimens and living plants, both in the wild and in
      cultivation in the experimental greenhouse, supports the recognition of the six
      new species, which are described and illustrated.

PMID- 28510817
TI  - Chemical characterization and antioxidative activity of four 3-hydroxyl-3
      methylglutaroyl (HMG)-substituted flavonoid glycosides from Graptopetalum
      paraguayense E. Walther.
AB  - BACKGROUND: Graptopetalum paraguayense E. Walther is a popular traditional
      Chinese herb and possesses several health benefits. In earlier studies, we
      demonstrated that G. paraguayense showed no genotoxicity and showed several
      biological activities. However, the constituents of G. paraguayense have not been
      studied yet. In this present study, we isolated and identified the constituents
      of the leaves of G. paraguayense E. Walther. RESULTS: A total of seven flavonoid
      compounds were isolated from the methanolic extract of G. paraguayense. The four
      major compounds isolated were flavonoid glucoside derivatives of quercetin (1, 3)
      and kampferol (2, 4), each presenting a 3-hydroxyl-3-methylglutaroyl (HMG)
      substituent; compounds 3 and 4-the 2''-acetyl derivatives of 1 and 2,
      respectively-are novel compounds isolated from nature for the first time. High
      performance liquid chromatography for the quantitative analyses of the four major
      HMG-substituted flavonoid glycosides in G. paraguayense E. Walther were
      accomplished to acquire the high yields of 1-4 in the methanolic extract (4.8,
      5.7, 4.3, and 2.5 mg/g, respectively). Furthermore, the antioxidant activities,
      including radical-scavenging, reducing power and lipid peroxidation inhibitory
      effects of these isolated flavonoids were also evaluated. All seven of the
      isolated flavonoid compounds possessed antioxdative activity. CONCLUSIONS: In
      this study of the constituents of the leaves of G. paraguayense E. Walther, we
      isolated four major components from its methanolic extract and determined their
      structures to be (acetylated) HMG-substituted flavonol glycosides, which are rare
      in nature. All seven of the isolated compounds possessed antioxdative activity,
      and those flavonoid compounds may be responsible for the functional ingredients
      in G. paraguayense. Further investigation of their bioactivities or
      pharmacological activities will be continued.

PMID- 28510819
TI  - Distyly and floral morphology of Psychotria cephalophora (Rubiaceae) on the
      oceanic Lanyu (Orchid) Island, Taiwan.
AB  - BACKGROUND: Psychotria cephalophora Merr. (Rubiaceae), a shrub in oceanic islands
      of Taiwan and the Philippines, appears to be distylous, but distyly is usually
      rare on oceanic islands. To elucidate the functional breeding system of P.
      cephalophora can improve our understanding of plant reproductive ecology on
      oceanic islands. RESULTS: Field investigations on Lanyu (Orchid Island) off the
      coast of southeastern Taiwan revealed the flowers to be distylous with short (S)-
      and long (L)-styled morphs, with only one morph per individual. Laboratory
      observations revealed that both morphs had stainable pollen grains and indicated
      dimorphism in stigmatic papillae and pollen size. In hand pollination
      experiments, the pollen tubes reached the base of the style in intermorph
      crossing, whereas they rarely penetrated stylar tissue in intramorph crossing and
      selfing. Open pollinated S- and L-styled flowers produced fruit. CONCLUSIONS: The
      results indicate that the breeding system of P. cephalophora is morphologically
      and functionally distylous.

PMID- 28510820
TI  - Ficus (Moraceae) and fig wasps (Hymenoptera: Chalcidoidea) in Taiwan.
AB  - Although Ficus-associated wasp fauna have been extensively researched in
      Australasia, information on these fauna in Taiwan is not well accessible to
      scientists worldwide. In this study, we compiled records on the Ficus flora of
      Taiwan and its associated wasp fauna. Initial agronomic research reports on Ficus
      were published in Japanese in 1917, followed by reports on applied biochemistry,
      taxonomy, and phenology in Chinese. On the basis of the phenological knowledge of
      15 species of the Ficus flora of Taiwan, recent research has examined the
      pollinating and nonpollinating agaonid and chalcid wasps (Hymenoptera:
      Chalcidoidea). Updating records according to the current nomenclature revealed
      that there are 30 taxa (27 species) of native or naturalized Ficus with an
      unusually high proportion of dioecious species (78%). Four species were observed
      to exhibit mutualism with more than one pollinating wasp species, and 18 of the
      27 Ficus species were reported with nonpollinating wasp species. The number of
      nonpollinating wasp species associated with specific Ficus species ranges from
      zero (F. pumila) to 24 (F. microcarpa). Approximately half of the Taiwanese fig
      tree species have been studied with basic information on phenology and biology
      described in peer-reviewed journals or theses. This review provides a solid basis
      for future in-depth comparative studies. This summary of knowledge will encourage
      and facilitate continuing research on the pollination dynamics of Ficus and the
      associated insect fauna in Taiwan.

PMID- 28510821
TI  - In vitro culture and production of syringin and rutin in Saussurea involucrata
      (Kar. et Kir.) - an endangered medicinal plant.
AB  - BACKGROUND: Saussurea involucrata (Kar. et Kir.) commonly known as 'snow lotus'
      or 'Xue Lian' is an important plant in the traditional Chinese system of
      medicine. The plant contains flavonoids such as syringin and rutin. These
      compounds have been reported to be anti-rheumatic, anti-inflammatory and dilate
      blood vessels, lower blood pressure, prevent cardiovascular diseases, enhance
      immunity, and act as anti-aging, anti-cancer, and anti-fatigue agents. The
      species has become endangered due to the excessive collection of S. involucrata
      plants in the wild, slower plant growth and ecological destruction of natural
      habitats. There is a severe shortage of plant material, while the market demand
      is ever increasing. Hence, it is very important to apply tissue culture technique
      for plant propagation and production of the bioactive compounds of this species.
      RESULTS: Multiple shoot induction and proliferation in shoot base explants
      derived from in vitro raised seedlings of S. involucrata was achieved on 3/4
      strength of Murashige and Skoog's (MS) basal medium (MSBM) supplemented with 1.0
      mg/L-1 BA and 1.5 mg/L-1 NAA. Rooting was induced in 100 % shoots cultured on
      1/2X MSBM supplemented with 1.0 mg/L-1 IBA for one week and then transfer to
      auxin free medium. The plantlets could be acclimatized successfully by sachet
      technique and established in the greenhouse. Maximum callus induction and
      proliferation in leaf segments was achieved on 1/2X MSBM supplemented with 0.5
      mg/L-1 BA, 0.5 mg/L-1 NAA, 0.4 % gelrite and on incubation at 20  degrees C.
      Container closures had an influence on the quality and quantity of callus and
      production of the active compounds. The HPLC analysis showed much higher syringin
      content in in vitro shoots and callus as compared to commercially available
      market crude drug. CONCLUSION: The present study describes an in vitro culture
      protocol of Saussurea involucrata. The bioactive compounds, syringin and rutin
      could be produced through tissue culture technique without sacrificing the
      endangered Saussurea involucrata plants in the wild.

PMID- 28510822
TI  - Antibacterial mechanism of the action of Enteromorpha linza L. essential oil
      against Escherichia coli and Salmonella Typhimurium.
AB  - BACKGROUND: Identification of natural antibacterial agents from various sources
      that can act effectively against disease causing foodborne bacteria is one of the
      major concerns throughout the world. However, the natural antibacterial agents
      identified to date are primarily effective against Gram positive bacteria, but
      less effective against Gram negative bacteria. In the present study, Enteromorpha
      linza L. essential oil (EEO) was evaluated for antibacterial activity against
      Escherichia coli and Salmonella Typhimurium along with the mode of their
      antibacterial action. RESULTS: The chemical composition of EEO revealed high
      amounts of acids (54.6 %) and alkenes (21.1 %). EEO was effective against both E.
      coli and S. Typhimurium. The minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) values of EEO for both pathogens were 12.5 mg/ml
      and 25.0 mg/mL, respectively. EEO at the MIC acted on the loss in viability of E.
      coli ATCC 43890, which was used as the model system for evaluation of the
      antibacterial mode of action of EEO against Gram negative bacteria. Significant
      increase in relative electrical conductivity and K+ concentration were recorded
      with respect to time, indicating the disruption of tested E. coli cells owing to
      the controlling effect of EEO. Alternation of the morphology of the cell surface,
      increase in the release of 260 nm absorbing materials and loss of high salt
      tolerance were observed. CONCLUSIONS: The results suggest that EEO induced a
      bactericidal effect via structural membrane damage caused by deposition of EEO in
      the cytosol or through enzymatic degradation of bacterial intracellular enzymes
      that resulted in cellular lysis. Accordingly, EEO can be used as a strong natural
      antibacterial agent against Gram negative foodborne pathogens such as E. coli and
      S. Typhimurium.

PMID- 28510823
TI  - Investigation of metabolites accumulation in medical plant Gentiana rigescens
      during different growing stage using LC-MS/MS and FT-IR.
AB  - BACKGROUND: Gentiana rigescens, an important medicinal plant in China, has been
      widely cultivated in Yunnan province, China. Previous studies were focused on
      analysis and determination of the metabolites isolated from this species, the
      accumulation of these metabolites during growth period are not yet clear. In this
      study, samples for the experiments were obtained by tissue culture. FT-IR and LC
      MS/MS method were performed to distinguish the variation on the major metabolites
      in G. rigescens during growing stage when combined with chemometrics. RESULTS:
      Methodology validations were all within the required limits. The metabolites were
      visually different in tissue culture samples and mature plants. The diversity of
      metabolites increased proportionally with plant growth. The quantitative analysis
      showed the content of gentiopicroside was significantly vary during different
      growing stage. The highest content of gentiopicroside (122.93 +/- 7.01 mg/g) was
      detected in leaf of regenerated plantlet, whereas its content in root
      significantly increased along with underground parts growth. Moreover, flavonoids
      mainly distributed in aerial parts showed potential competitive relationship
      during plant growth. CONCLUSION: The distribution and accumulation of metabolites
      are associated with different parts and plant growth, which provide potential
      evidences for the rational application and exploitation of G. rigescens.

PMID- 28510824
TI  - Scale-dependent effects of habitat fragmentation on reproduction in the annual
      Circaeaster agristis, a narrow endemic and threatened species.
AB  - BACKGROUND: Habitat fragmentation and the resulting decline in population size
      and density commonly reduce the reproduction of rare and threatened species. We
      investigated the impacts of population size and density on reproduction in more
      than 30 populations of Circaeaster agristis, a narrow endemic and threatened
      species, in 2010 and 2011. We also examined the effects of NND (nearest neighbor
      distance) and LNS (local neighbor size), within radii of 0.1 m, 0.2 m and 0.3 m,
      on reproduction in two of the populations in 2011. RESULTS: Population size did
      not affect fruit (seed) number and fruit set in either year studied. Population
      density had an indirect negative effect on fruit number and fruit set as a
      consequence of a negative effect on plant size in 2010, but had no effect on
      fruit number and fruit set in 2011. Within populations, individual fruit number
      did not change, and individual fruit set increased independent of plant size, in
      response to increasing NND. Both individual fruit number and individual fruit set
      increased, independent of plant size, with increases in LNS within a 0.1 m
      radius, but did not change with increases in LNS within radii of between 0.1 m
      and 0.2 m radii or between 0.2 m and 0.3 m. CONCLUSIONS: The effect of habitat
      fragmentation on reproduction of C. agristis is scale-dependent. In contrast to
      the generally accepted idea that fragmentation reduces plant reproduction,
      reproductive success may increase in sparse populations or increase in response
      to decreases in LNS in C. agristis.

PMID- 28510825
TI  - Antimicrobial activity and mechanisms of Salvia sclarea essential oil.
AB  - BACKGROUND: Nowadays, essential oils are recognized as safe substances and can be
      used as antibacterial additives. Salvia sclarea is one of the most important
      aromatic plants cultivated world-wide as a source of essential oils. In addition
      to being flavoring foods, Salvia sclarea essential oil can also act as
      antimicrobials and preservatives against food spoilage. Understanding more about
      the antibacterial performance and possible mechanism of Salvia sclarea essential
      oil will be helpful for its application in the future. But so far few related
      researches have been reported. RESULTS: In our study, Salvia sclarea oil showed
      obvious antibacterial activity against all tested bacterial strains. Minimum
      inhibitory concentration (MIC) and minimum bactericide concentration (MBC) of
      seven pathogens were 0.05 and 0.1 % respectively. In addition, Salvia sclarea oil
      also exhibited a significant inhibitory effect on the growth of Escherichia coli
      (E. coli) in phosphate buffer saline (PBS) and meats. After treated with Salvia
      sclarea oil, Scanning Electron Microscope (SEM) images can clearly see the damage
      of cell membrane; the intracellular ATP concentrations of E. coli and S. aureus
      reduced 98.27 and 69.61 % respectively, compared to the control groups; the
      nuclear DNA content of E. coli and S. aureus was significantly reduced to 48.32
      and 50.77 % respectively. In addition, there was massive leakage of cellular
      material when E. coli and S. aureus were exposed to Salvia sclarea oil.
      CONCLUSIONS: Salvia sclarea essential oil damaged the cell membrane and changed
      the cell membrane permeability, leading to the release of some cytoplasm such as
      macromolecular substances, ATP and DNA. In general, the antimicrobial action of
      Salvia sclarea essential oil is not only attributable to a unique pathway, but
      also involves a series of events both on the cell surface and within the
      cytoplasm. Therefore, more experiments need to be done to fully understand the
      antimicrobial mechanism of Salvia sclarea essential oil.

PMID- 28510826
TI  - Effects of hot-water extracts from Ganoderma lucidum residues and solid-state
      fermentation residues on prebiotic and immune-stimulatory activities in vitro and
      the powdered residues used as broiler feed additives in vivo.
AB  - BACKGROUND: Large amounts of Ganoderma lucidum (GL) commercial products are
      provided in the worldwide market such as powders, tea bags, or capsules as
      dietary supplements which contained triterpenoids and/or polysaccharides.
      Therefore, it was estimated that several thousand tons of GL residues (GLR) are
      produced and discarded. For recycling uses, the aim of this study was to evaluate
      the benefits of two hot-water extracts from GLR (HWP_GLR) and solid-state
      fermentation GLR inoculated with GL mycelia (HWP_GLRF) on the growths of
      Lactobacillus rhamnosus and Bifidobacterium longum. The RAW264.7 cells were used
      to investigate the effects of HWP_GLR and HWP_GLRF on nitric oxide productions,
      phagocytic activities against FITC-labeled E. coli, and to lower
      lipopolysaccharide (LPS)-binding capacities. The powders of GLR and GLRF were
      used as additives in the commercial feeds for feeding broiler chicks in vivo to
      evaluate the immune-stimulatory and prebiotic activities. RESULTS: HWP_GLR and
      HWP_GLRF with molecular size 5 to 8 kDa were showed to stimulate growths of L.
      rhamnosus and B. longum. It was found that in the presence of polymyxin B HWP_GLR
      and HWP_GLRF could stimulate nitric oxide productions, elevate phagocytic
      activities against FITC-labeled E. coli, and to lower lipopolysaccharide-binding
      capacities in RAW264.7 cells. The broiler chicks were selected for feedings in
      vivo. The 1-day-old chicks were fed commercial feeds for 1 week, and then were
      fed without or with 4 or 8 % of GLR and GLRF additives for 3 weeks. There was no
      significant weight difference among feeding groups. However, the phagocytosis and
      natural killer cytotoxicity in the peripheral bloods, and prebiotic activities of
      bifidobacteria in feces of GLR and/or GLRF groups were significantly different
      compared to the control (P < 0.05). CONCLUSIONS: The GLR, GLRF, and their hot
      water extracts with beneficial activities could be processed as feed additives
      which could increase the waste-recycling.

PMID- 28510827
TI  - Proteomic analysis of broccoli (Brassica oleracea) under high temperature and
      waterlogging stresses.
AB  - BACKGROUND: The production of broccoli (Brassica oleracea) is largely reduced by
      waterlogging and high temperature stresses. Heat-tolerant and heat-susceptible
      broccoli cultivars TSS-AVRDC-2 and B-75, respectively, were used for
      physiological and proteomic analyses. The objective of this study was to identify
      TSS-AVRDC-2 and B-75 proteins differentially regulated at different time periods
      in response to waterlogging at 40  degrees C for three days. RESULTS: TSS-AVRDC-2
      exhibited significantly higher chlorophyll content, lower stomatal conductance,
      and better H2O2 scavenging under stress in comparison to B-75. Two-dimensional
      liquid phase fractionation analyses revealed that Rubisco proteins in both
      varieties were regulated under stressing treatments, and that TSS-AVRDC-2 had
      higher levels of both Rubisco large and small subunit transcripts than B-75 when
      subjected to high temperature and/or waterlogging. CONCLUSIONS: This report
      utilizes physiological and proteomic approaches to discover changes in the
      protein expression profiles of broccoli in response to heat and waterlogging
      stresses. Higher levels of Rubisco proteins in TSS-AVRDC-2 could lead to
      increased carbon fixation efficiency to provide sufficient energy to enable
      stress tolerance under waterlogging at 40  degrees C.

PMID- 28510828
TI  - Three new species of Begonia endemic to the Puerto Princesa Subterranean River
      National Park, Palawan.
AB  - BACKGROUND: Begonia is a mega-diverse genus of flowering plants prone to
      generating micro-endemic species, especially on limestone habitats. During
      fieldwork in the Puerto Princesa Subterranean River National Park, Palawan
      (Philippines), three species were encountered which did not match any previously
      described from the region. RESULTS: Following morphological, anatomical,
      molecular phylogenetic and cytological investigation a hypothesis of three new
      species is supported. The three new species belong to a clade endemic to Palawan
      and Borneo. CONCLUSIONS: The limestone habitats in the Puerto Princesa
      Subterranean River National Park environs support a unique flora. The description
      of three new species from a small area within the park demonstrates how much
      remains to be discovered there, and the importance of its continued protection.

PMID- 28510829
TI  - Cambial activity and xylogenesis in stems of Cedrus libani A. Rich at different
      altitudes.
AB  - BACKGROUND: The dynamics of cambial activity and xylogenesis provide information
      on how and to what extent wood formation respond to climatic variability. The
      Lebanon Cedar (Cedrus libani A.Rich) is a montane tree species which is
      distributed along a wide altitudinal range in the northeastern Mediterranean
      region, currently considered as a potential forest species for Central Europe
      with respect to climate change. This study provides first data on intra-annual
      growth dynamics at cellular level using the microcore technique for a montane
      Mediterranean tree species at different altitudes within and outside its natural
      range. RESULTS: Microcores were collected fortnightly in the growing season of
      2013 in order to study temporal dynamics of cambial activity and xylogenesis in
      stems of C. libani at different altitudes in the Taurus Mountains (1000 - 2000 m
      a.s.l.) and at a plantation at Bayreuth (330 m a.s.l.; Germany). The dormant
      cambium consisted of about 5 cells at the Turkish sites and 7 cells at Bayreuth.
      Cambial activity set in, when daily minimum temperatures exceeded 0  degrees C
      and daily means of air and stem temperature exceeded 5  degrees C. Xylogenesis
      started between April and May, ended approximately the end of September to the
      beginning of October and lasted 134 (at tree line) to 174 days (at the lowest
      Turkish site). Mean ring widths varied from 0.55 to 3.35 mm, with highest values
      observed at Bayreuth very likely resulting from a steady water supply during
      growing season. Means of daily cell production rates varied from 0.73 to 0.12.
      Samples containing traumatic resin ducts occurred only rarely and where not used
      for analysis. CONCLUSIONS: In C. libani, onset and dynamics of cambial activity
      and xylogenesis are triggered by daily means of stem and air temperatures whereas
      water availability has a higher influence on growth rates and cessation of wood
      formation. Within sites, duration of xylogenesis does not significantly differ
      with respect to age and tree size. C. libani grows well outside its natural range
      and thus may be a promising species for forestation in Central Europe with
      respect to climate change. We suggest further studies on if/how traumatic resin
      ducts influence tree ring width.

PMID- 28510830
TI  - Arabidopsis Qc-SNARE genes BET11 and BET12 are required for fertility and pollen
      tube elongation.
AB  - KEY MESSAGE: BET11 and 12 are required for pollen tube elongation. Pollen tubes
      are rapidly growing specialized structures that elongate in a polar manner. They
      play a crucial role in the delivery of sperm cells through the stylar tissues of
      the flower and into the embryo sac, where the sperm cells are released to fuse
      with the egg cell and the central cell to give rise to the embryo and the
      endosperm. Polar growth at the pollen tube tip is believed to result from
      secretion of materials by membrane trafficking mechanisms. In this study, we
      report the functional characterization of Arabidopsis BET11 and BET12, two genes
      that may code for Qc-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors). Double mutants (bet11/bet12) in a homozygous/heterozygous
      background showed reduced transmission of the mutant alleles, reduced
      fertilization of seeds, defective embryo development, reduced pollen tube lengths
      and formation of secondary pollen tubes. Both BET11 and BET12 are required for
      fertility and development of pollen tubes in Arabidopsis. More experiments are
      required to dissect the mechanisms involved.

PMID- 28510832
TI  - Chromosome numbers of populations of three varieties of Bidens pilosa in Taiwan.
AB  - BACKGROUND: Hairy beggar-ticks (Bidens pilosa L.) is a common invasive plant in
      tropical and subtropical regions. The Flora of Taiwan listed three varieties of
      B. pilosa in Taiwan, var. minor, var. pilosa and var. radiata. Among the three
      varieties, var. radiata was the most recently, in 1970s, introduced into Taiwan.
      However, after its introduction into Taiwan, var. radiata has become dominant
      over the other two varieties and is considered a serious invasive plant in
      lowland of Taiwan. Our previous study showed that var. radiata is self
      incompatible and the other two varieties are self-fertile. Could it be possible
      that different chromosome numbers contribute to the different breeding systems of
      these three varieties? In addition, the heterogeneities of traits of var. radiata
      were found higher than those of var. minor and var. pilosa. Is the phenomenon
      resulting from the hybridization between var. radiata with other varieties? We
      counted chromosome numbers of populations of these three varieties distributed in
      Taiwan and conducted hand pollination treatment between var. radiata (as pollen
      receiver) and var. minor or var. pilosa (as pollen donor) to provide answer for
      the aforementioned questions. RESULTS: No difference was found in chromosome
      numbers among populations of the same variety. Forty-eight chromosomes (2n = 48)
      were counted for var. radiata while 72 (2n = 72) chromosomes for var. minor and
      var. pilosa. Therefore, var. radiata is tetraploid and var. minor and var. pilosa
      are hexaploid. No successful hybridization was found between var. radiata and
      var. minor or between var. radiata and var. pilosa. CONCLUSIONS: This study
      provided the evidence that the invasive plant (B. pilosa var. radiata) has
      different chromosome numbers from the other two varieties and is unlikely to
      hybridize with the other two varieties.

PMID- 28510831
TI  - Distribution of new satellites and simple sequence repeats in annual and
      perennial Glycine species.
AB  - The repeat sequences occupied more than 50 % of soybean genome. In order to
      understand where these repeat sequences distributed in soybean genome and its
      related Glycine species, we examined three new repeat sequences-soybean repeat
      sequence (SBRS1, SBRS2 and SBRS3), some nonspecific repeat sequences and 45S rDNA
      on several Glycine species, including annual and perennial accessions in this
      study. In the annual species, G. soja, signals for SBRS1 and ATT repeat can be
      found on each chromosome in GG genome, but those for SBRS2 and SBRS3 were located
      at three specific loci. In perennial Glycine species, these three SBR repeat
      frequently co-localized with 45S rDNA, two major 45S rDNA loci were found in all
      tetraploid species. However, an extra minor locus was found in one accession of
      the G. pescadrensis (Tab074), but not in another accession (Tab004). We
      demonstrate that some repetitive sequences are present in all Glycine species
      used in the study, but the abundancy is different in annual or perennial species.
      We suggest this study may provide additional information in investigations of the
      phylogeny in the Glycine species.

PMID- 28510833
TI  - Phenolic constituents and antioxidant properties of five wild species of Physalis
      (Solanaceae).
AB  - BACKGROUND: Fruits of wild species of the genus Physalis are consumed as food and
      calyces and leaves are used in traditional medicine. The phenolic composition of
      the species of this genus have been scarcely studied. To contribute to a better
      knowledge for the use of all the potential of these wild species of plants,
      leaves, fruits, and calyces of five wild species of the genus were analyzed for
      their phenolic composition and antioxidant properties. RESULTS: Important tissue-
      and species-dependent variations were found. Calyces of Physalis subulata showed
      the highest contents of phenolics (176.58 mg of gallic acid equivalents/g dry
      tissue), flavonoids (39.63 mg/g dry tissue), and phenolic acids (50.57 mg of
      quercitrin equivalents/g dry tissue), and its leaves displayed the highest total
      antioxidant capacity (3.59 mg of ascorbic acid equivalents/mL) and one of the
      highest reduction powers (0.54 ug of ascorbic acid equivalents/mL). A high
      performance liquid chromatography with photodiode array detection analysis
      revealed a total of 28 phenolic compounds in foliar tissues (mainly kaempferol-3
      O-glycosides), 16 in fruits (mainly phenolic acids), and 16 in calyces (mainly
      kaempferol-3-O-glycosides); the profiles of these compounds in the three types of
      tissue were species-specific. CONCLUSIONS: The studied species of Physalis are
      important sources of phenolics with relevant antioxidant activity. The current
      results indicate that phenolic profiles are valuable specific chemical markers
      and can be relevant as food tracing and authenticity indicators for plant-based
      preparations involving species of Physalis.

PMID- 28510834
TI  - The seasonal variations of allelopathic activity and allelopathic substances in
      Brachiaria brizantha.
AB  - BACKGROUND: Controlling weeds through allelopathy is one strategy to reduce
      dependency on synthetic herbicides. The plant shoots of the grass Brachiaria
      brizantha incorporated into the field soil were found to inhibit the growth of
      several plant species. We investigated the variations of allelopathic activity
      and allelopathic substances in B. brizantha harvested in June, October and
      January. RESULTS: All extracts of B. brizantha obtained from June, October and
      January inhibited the root and shoot growth of cress, lettuce, Phleum pretense
      and Lolium multiflorum in a concentration dependent manner. However, the
      inhibitory activity of B. brizantha of June and October was greater than that of
      B. brizantha of January. Concentrations of three potent allelopathic active
      substances, (6R,9S)-3-oxo-alpha-ionol, (6R,9R)-3-oxo-alpha-ionol and 4
      ketopinoresinol were also greater in B. brizantha of June and October than those
      in B. brizantha of January. CONCLUSION: The results suggest that the allelopathic
      activity and the levels of those allelopathic active substances are greater in B.
      brizantha of June and October than those in B. brizantha of January. It is
      possible that B. brizantha could be useful for a weed suppressive residue or soil
      additive materials in the variety of agricultural settings to develop sustainable
      agriculture options. The effectiveness of B. brizantha of June and October as a
      weed suppressive agent may be greater than that of January.

PMID- 28510835
TI  - Plant bioclimatic models in climate change research.
AB  - Bioclimatics is an ancient science that was once neglected by many ecologists.
      However, as climate changes have attracted increasing attention, scientists have
      reevaluated the relevance of bioclimatology and it has thus become essential for
      exploring climate changes. Because of the rapidly growing importance of
      bioclimatic models in climate change studies, we evaluated factors that influence
      plant bioclimatology, constructed and developed bioclimatic models, and assessed
      the precautionary effects of the application of the models. The findings obtained
      by sequentially reviewing the development history and importance of bioclimatic
      models in climate change studies can be used to enhance the knowledge of
      bioclimatic models and strengthen their ability to apply them. Consequently,
      bioclimatic models can be used as a powerful tool and reference in decision
      making responses to future climate changes. The objectives of this study were to
      (1) understand how climatic factors affect plants; (2) describe the sources,
      construction principles, and development of early plant bioclimatic models
      (PBMs); and (3) summarize the recent applications of PBMs in climate change
      research.

PMID- 28510837
TI  - Range extension of Christisonia scortechinii from mainland Southeast Asia into
      Borneo, and notes on the distinction between Aeginetia and Christisonia
      (Orobanchaceae).
AB  - BACKGROUND: Christisonia is a little-documented and poorly studied root-parasitic
      genus in the Orobanchaceae occurring in India, China, Indochina and part of the
      Malesian region. Recent collection of a Christisonia taxon in Kinabalu Park in
      Sabah, Borneo, taxonomically identical to earlier Sabah collections that have
      hitherto not been recorded in the literature, led to an assessment of the
      taxonomic identity of the species against Christisonia scortechinii, C.
      siamensis, C. sinensis and related species. RESULTS: Some taxa in China,
      Indochina, the Malay Peninsula, and the Philippines are morphologically identical
      to the Borneo taxon except in the number of calyx lobes, but differ by several
      distinctive characters from other well-distinguished species in the region.
      Studies of dried herbarium specimens, augmented by photographic images of
      different stages of fresh flowering material and a scrutiny of available
      descriptions confirmed that the calyx has two primary lobes in the bud that may
      separate into 3-5 portions, giving a variable number of apparent lobes in
      specimen material collected at different localities. This new scrutiny of the
      calyx also permitted an improved description of the calyx differences that
      separate Christisonia and the closely related Aeginetia, which have not been
      clearly elucidated in the past. CONCLUSIONS: Christisonia scortechinii Prain
      (Orobanchaceae), the only species that was described as having an initially
      spathaceous calyx among species of this root-parasitic genus, is newly recorded
      for Borneo (including Kinabalu Park, where its presence has been overlooked). The
      range of the species in mainland Southeast Asia, previously extended from
      Peninsular Malaysia to Thailand and Vietnam, is here further extended to Laos and
      China. Christisonia wightii Elmer (relevant to the Philippines) and C. sinensis
      Beck (China) are reduced to synonymy.

PMID- 28510836
TI  - Great fraction of dissolved organic C and N in the primary per-humid
      Chamaecyparis forest soil.
AB  - BACKGROUND: Labile organic matter plays a crucial role in a variety of forest
      functions, however, our understanding to its quality and quantity across various
      forests is limited, particularly primary forests. We investigated soil labile C
      and N (i.e. microbial biomass C and N, dissolved organic carbon (DOC) and
      nitrogen (DON), associated ammonium, and nitrate) at three topographic locations
      (i.e. summit, footslope and lakeshore) in a primary Chamaecyparis forest of
      Taiwan. The following hypotheses are tested in this study: (1) This undisturbed
      Chamaecyparis forest shows the great size of soil labile C and N; (2) there is an
      evident topographic effect on the distribution of soil labile C and N and the
      associated inorganic N over seasons. RESULTS: Fulfilling with our first
      hypothesis, the considerable size of labile C and N in this forest soil was
      quantified. Abundant C availability and the acidity of soils in this forest
      favoured ammonium production over nitrate. The undisturbed environment with per
      humid and acidic soil was linked to the high concentrations of soil DOC and DON
      as the dominant form in N dynamics. In contrast to our second hypothesis,
      topographic effects on soil labile C and N were generally not evident, suggesting
      the homogeneous soil environment across various topographic locations in this
      Chamaecyparis forest. CONCLUSIONS: This study illustrates the sustainable
      importance of primary montane forests for being sources of DOC and DON.

PMID- 28510838
TI  - Impatiens pandurata (Balsaminaceae), a new species from Yunnan, China.
AB  - BACKGROUND: The species-rich genus Impatiens is mainly distributed throughout
      much of tropical Africa, India, southwest Asia, southern China and Japan. There
      are more than 270 species recorded in China, most of which are restricted to the
      southwest. An unknown species of Impatiens was collected from Yunnan, southwest
      China. RESULTS: Impatiens pandurata Y. H. Tan & S. X. Yu, a new species of
      Balsaminaceae from Jinping County and Malipo County, Yunnan, China is similar to
      I. apalophylla and I. clavigera in having racemose inflorescences, 4 lateral
      sepals, hammer-shaped capsules and ellipsoid seeds, but differs in having leaves
      with oblanceolate blades aggregated at the top of the stem, 3-5-flowered racemes,
      a yellow lower sepal without reddish patches, yellowish flowers, and a dorsal
      petal with stalks at the base. Molecular phylogenetic analyses of sequences from
      both nuclear ribosomal and plastid genes confirm that this new species is
      distinct from morphologically similar species previously recorded. CONCLUSION:
      With the support of careful morphological studies and phylogenetic analysis, I.
      pandurata is a species new to science.

PMID- 28510839
TI  - Two rare ophiocordycipitaceous fungi newly recorded in Taiwan.
AB  - BACKGROUND: Ophiocordycipitaceae is a highly diverse fungal family parasitizing a
      wide range of arthropods and hypogeous fungi. We collected two
      ophiocordycipitaceous species previously unknown in Taiwan: one emerged from
      hypogeous fruiting bodies of an Elaphomyces fungus and the other was associated
      with dragonflies. RESULTS: Based on gross morphology, microscopic features, ITS
      sequences, and hosts, the two ophiocordycipitaceous fungi were identified as
      Tolypocladium japonicum and Ophiocordyceps odonatae. We isolated axenic cultures
      of these two fungi, and their anamorphs were obtained. The simplicillium-like
      anamorph of T. japonicum is described herein for the first time. The anamorph of
      O. odonatae produce conidia holoblastically in sympodial sequence and is
      assignable to Hymenostilbe. A dichotomous key to the species of
      Ophiocordycipitaceae reported in Taiwan is provided. CONCLUSION: A thorough
      literature study indicates that the two fungi reported herein have rarely been
      collected. Our identifications of T. japonicum and O. odonatae agree well with
      descriptions in the literature and are highly supported by DNA sequence analysis.

PMID- 28510840
TI  - Two conserved oligosaccharyltransferase catalytic subunits required for N
      glycosylation exist in Spartina alterniflora.
AB  - BACKGROUND: Asparagine (N)-linked glycosylation is one of the most crucial post
      translational modifications, which is catalyzed in the lumen of the endoplasmic
      reticulum (ER) by the oligosaccharyltransferase (OST) in eukaryotic cells.
      Biochemical and genetic assay leads to the identification of the nine subunits
      (Ost 1-6, Stt3, Swp1 and Wbp1) of the yeast OST and in which Stt3p is proposed
      playing a central and conserved role in N-glycosylation. Two STT3 isoform genes,
      STT3A and STT3B, exist in the plant and mammal genomes. OST with different
      catalytic STT3 isoforms has different enzymatic properties in mammals. The
      mutation of STT3A in Arabidopsis thaliana causes a salt hypersensitive phenotype
      the inhibited root growth and swollen root tips suggesting protein N
      glycosylation is indispensable for plant growth and development. Spartina
      alterniflora is widely used for shoreline protection and tidal marsh restoration
      due to the strong salt tolerance although the exact molecular mechanism is little
      known. To explore the possible biological roles of N-glycosylation in plant
      adaptive resistance to salinity stress, we cloned the STT3 genes from S.
      alterniflora and heterogenously expressed them in Arabidopsis mutant to observe
      the functional conservation. RESULTS: SaSTT3A and SaSTT3B genes were cloned from
      Spartina alterniflora. SaSTT3A genomic sequences spanned over 23 exons and 22
      introns, while SaSTT3B had 6 exons and 5 introns. The gene structures of both
      genes were conserved among the analyzed plant species. Subcellular localization
      and transmembrane structure prediction revealed that these two genes had 13 and
      11 transmembrane helices respectively. The functional complementation in which
      the cDNA of SaSTT3A and SaSTT3B driven by CaMV 35S promoter completely or
      partially rescued Arabidopsis stt3a-2 mutant salt-sensitive phenotype, indicating
      STT3A functions conservatively between glycophyte and halophyte and N
      glycosylation might be involved in plant resistance to salinity. CONCLUSIONS: Two
      STT3 isoform genes, SaSTT3A and SaSTT3B, were cloned from S. alterniflora and
      they were evolutionally conserved at gene structure and coding sequences compared
      with their counterparts. Moreover, SaSTT3 genes could successfully rescue
      Arabidopsis stt3a-2 salt-sensitive phenotype, suggesting there exists a similar N
      glycosylation process in S. alterniflora. Here we provided a first piece of
      evidence that the N-glycosylation might be involved in salt tolerance of
      halophyte.

PMID- 28510841
TI  - Sexual specialization in phenology in dioecious Ficus benguetensis and its
      consequences for the mutualism.
AB  - BACKGROUND: Timing of reproductive events has become central in ecological
      studies linking success in pollination and seed dispersion to optimizing the
      probability and periods of encounters with pollinators or dispersers. Obligate
      plant-insect interactions, especially Ficus-fig wasp mutualisms, offer striking
      examples of fine-tuned encounter optimization as biological cycles between
      mutualistic partners are deeply dependent on each other and intertwined over
      generations. Despite fig flowering phenology being crucial in maintaining Ficus
      fig wasp mutualisms, until now, the forces of selection shaping the phenological
      evolution of dioecious fig trees have received little attention. By conducting a
      2-year survey of a population of Ficus benguetensis in Northern Taiwan, we
      assessed whether environmental factors or other selective pressures shape the
      phenology of male and female fig trees. RESULTS: Constraints by mutualistic
      pollinating wasps and seed dispersers, rather than climatic factors, appeared to
      mainly shape fig phenology and allometry in F. benguetensis. We identified a new
      sexual specialization in dioecious fig trees: the position of fig production. We
      propose that the continuous male fig production on tree trunks can enhance the
      survival of pollinating fig wasps through faster localization of receptive figs
      while reducing the mutualistic conflict between the fig and its obligate
      pollinators. By contrast, in female trees, fig production is massive in summer,
      located on the twigs of the foliar crown and seem more related to seed dispersal
      and germination. CONCLUSIONS: Identifying variations in the allometry and
      phenology of dioecious figs provide valuable insights into how monoecious and
      dioecious species resolve mutualism conflicts and into the emergence of dioecy in
      fig trees.

PMID- 28510842
TI  - Arabidopsis SFAR4 is a novel GDSL-type esterase involved in fatty acid
      degradation and glucose tolerance.
AB  - BACKGROUND: SFARs (seed fatty acid reducers) belonging to the GDSL
      lipases/esterases family have been reported to reduce fatty acid storage and
      composition in mature Arabidopsis seeds. GDSL lipases/esterases are hydrolytic
      enzymes that possess multifunctional properties, such as broad substrate
      specificity, regiospecificity, and stereoselectivity. Studies on the
      physiological functions and biochemical characteristics of GDSL lipases/esterases
      in plants are limited, so it is important to elucidate the molecular functions of
      GDSL-type genes. RESULTS: We found that SFAR4 (At3g48460), a fatty acid reducer
      belonging to the Arabidopsis GDSL lipases/esterases family, was intensely
      expressed in embryo protrusion, early seedlings, and pollen. The characterization
      of recombinant SFAR4 protein indicated that it has short-length p-nitrophenyl
      esterase activity. In addition, SFAR4 enhanced the expression of genes involved
      in fatty acid metabolism during seed germination and seedling development. SFAR4
      elevated the expression of COMATOSE, which transports fatty acids into
      peroxisomes, and of LACS6 and LACS7, which deliver long-chain acetyl-CoA for beta
      oxidation. Furthermore, SFAR4 increased the transcription of PED1 and PNC1, which
      function in importing peroxisomal ATP required for fatty acid degradation. SFAR4
      has another function on tolerance to high glucose concentrations but had no
      significant effects on the expression of the glucose sensor HXK1. CONCLUSIONS:
      The results demonstrated that SFAR4 is a GDSL-type esterase involved in fatty
      acid metabolism during post-germination and seedling development in Arabidopsis.
      We suggested that SFAR4 plays an important role in fatty acid degradation, thus
      reducing the fatty acid content.

PMID- 28510843
TI  - Three new species of Primulina (Gesneriaceae) from limestone karsts of China
      based on morphological and molecular evidence.
AB  - BACKGROUND: With more than 160 described species, Primulina is one of the most
      characteristic plant groups of the Sino-Vietnamese limestone flora. In our
      continous botanical inventory of the limestone flora of South China, we collected
      three new Primulina species not identifiable to known species. RESULTS: Molecular
      phylogenetic analyses based on nuclear ITS and chloroplast trnL-F and trnH-psbA
      sequences strongly support the placement the three new species in Primulina. In
      addition to morphological differences, DNA sequences of all these three new
      species show substantial divergencies, sustaining the recognition of these three
      new species. CONCLUSIONS: Based on morphological and molecular data, we describe
      and illustrate three new Primulina species: P. maculata, P. pengii, and P.
      yangshanensis.

PMID- 28510844
TI  - Influence of alpha-terpineol on the growth and morphogenesis of Penicillium
      digitatum.
AB  - BACKGROUND: Plant essential oils could act effectively against postharvest
      diseases, alpha-terpineol, a typical terpenoid of plant essential oils, exhibited
      strong antifungal activity in against Penicillium italicum, but the possible
      action mechanism remains undetermined. In present study, alpha-terpineol was
      evaluated for antibacterial activity against Penicillium digitatum along with the
      mode of their antibacterial action. RESULTS: The results showed that mycelial
      growth of P. digitatum was strongly inhibited by alpha-terpineol, with the
      minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC)
      of 2.00 and 8.00 ul/ml, respectively. Scanning electron microscopy observation
      revealed that alpha-terpineol obviously altered the morphology of P. digitatum
      hyphae by causing the loss of cytoplasm and distortion of mycelia. A rapid
      increase in the membrane permeability of P. digitatum was observed after treated
      with MIC or MFC of alpha-terpineol, evidenced by the release of cell
      constituents, the extracellular conductivity, and the extracellular pH. In
      addition, alpha-terpineol apparently induced a decrease in total lipid contents
      of P. digitatum cells, indicating the destruction of cell membrane structures
      after treatment. CONCLUSIONS: Based on our study, alpha-terpineol might affect
      the cell wall synthesis and lead to the disruption of cell wall. The cell wall
      disruption affected fungal morphogenesis, the integrity of membrane and leakage
      of intracellular components, these results suggested that alpha-terpineol
      treatment inhibited the growth of P. digitatum.

PMID- 28510845
TI  - Effect of potassium deficiency on antioxidant status and cadmium toxicity in rice
      seedlings.
AB  - BACKGROUND: Cadmium (Cd) is one of the most toxic heavy metals and inhibits
      physiological processes of plants. Potassium (K) is an essential macronutrient in
      plants. K deficiency and Cd stress represent two different abiotic stress
      conditions that occur in the field simultaneously. In this study, effects of K
      deficiency on antioxidant status and Cd toxicity in rice seedlings were
      investigated. RESULTS: K deficiency significantly decreased K concentration in
      shoots and roots. However, fresh weight and dry weight of rice seedlings were not
      affected by K deficiency. The activities of antioxidant enzymes (superoxide
      dismutase, ascorbate peroxidase, glutathione reductase, and catalase) in K
      deficient leaves were higher than respective control leaves. However, K
      deficiency had no effect on the content of antioxidants (ascorbate and
      glutathione). Cd toxicity was judged by the decrease in biomass production,
      chlorosis, and induction of oxidative stress. Based on these criteria, we
      demonstrated that K deficiency protected rice seedling from Cd stress. Moreover,
      chlorophyll concentration was higher in K-deficient shoots and roots than their
      respective control shoots and roots. CONCLUSIONS: Our results indicated that K
      deficiency protects rice seedlings from Cd toxicity. This protective effect of K
      deficiency is mainly due to enhanced antioxidant enzyme activities but not
      inhibition of Cd uptake.

PMID- 28510846
TI  - Reproductive phenology and pre-dispersal fruit predation in Atriplex halimus L.
      (Chenopodiaceae).
AB  - BACKGROUND: The flowering phenology pattern of Atriplex halimus was studied in a
      Mediterranean habitat in order to analyze protandry effectiveness. Fruit set
      evolution was recorded over two years and the impact of pre-dispersal predation
      by insects was also evaluated. RESULTS: The flowering phenology coincided in 2006
      and 2007, starting in mid-July and reaching full flowering at the end of August
      in both years. Inflorescences are composed of glomerules with 8.78 +/- 2.79 male
      flowers and 4.57 +/- 2.58 female flowers, with no significant differences in
      position on the inflorescence. The peaks of male and female flower anthesis were
      reached in mid-August, but the male maximum occurred one week before the female.
      Plants at the start of flowering only bear male flowers, but female flowers soon
      appear. Fruit set starts at the end of August; all the flowers were transformed
      into fruit by mid-September and their development continued to the beginning of
      October, when fruit structures had matured and began to drop. Fruit predation
      started at the end of September and reached maximum intensity in mid-October.
      CONCLUSIONS: At population level, male and female flowers seemed to open in the
      same weeks, but at plant and glomerule level male flowers opened one week before
      the females. Fruit predation levels were 62.42 and 43.14% in 2006 and 2007
      respectively, with no significant differences between different parts of the
      inflorescence. And larvae of Coleophoridae were the most abundant predators.

PMID- 28510847
TI  - Characterization of the decline and recovery of heat-treated Scenedesmus
      vacuolatus.
AB  - BACKGROUND: To find out how algal cells cope with and recover from heat stress,
      the small vegetative cells of the synchronous Scenedesmus vacuolatus culture were
      subjected to a heat pretreatment (46.5 degrees C for 1 h) followed by dark
      recultivation. The changes in physiological activities and morphology of
      Scenedesmus cells were continuously monitored throughout the course of decline
      and recovery. RESULTS: It was found that the heat treatment, though completely
      inhibited photosynthesis, did not kill Scenedesmus cells. These cells, during
      dark recultivation, could make a fast repair and regained the ability of
      proliferation. We suggest that they entered a 'stand-by' state, which was
      characterized by condensed chromatin, partially functional but morphologically
      altered chloroplasts, disappeared vacuoles, slightly shrunk protoplast and intact
      plasma membranes. These stressed cells, on the surface, seemingly were undergoing
      some kind of disintegration, could readily and quickly return to normal cells
      upon illumination. Cell death occurred only after a long period of darkness (>48
      h). CONCLUSIONS: Our results suggest that the recovery of algal cells from stress
      damage may actually proceed in two steps. The middle "stand-by' stage normally is
      gone through too rapidly to be detected unless cells are kept in the dark.

PMID- 28510848
TI  - Cytokinin, auxin, and abscisic acid affects sucrose metabolism conduce to de novo
      shoot organogenesis in rice (Oryza sativa L.) callus.
AB  - BACKGROUND: Shoot regeneration frequency in rice callus is still low and highly
      diverse among rice cultivars. This study aimed to investigate the association of
      plant hormone signaling and sucrose uptake and metabolism in rice during callus
      induction and early shoot organogenesis. The immatured seeds of two rice
      cultivars, Ai-Nan-Tsao 39 (ANT39) and Tainan 11 (TN11) are used in this study.
      RESULTS: Callus formation is earlier, callus fresh weight is higher, but water
      content is significant lower in ANT39 than in TN11 while their explants are
      inoculated on callus induction medium (CIM). Besides, the regeneration frequency
      is prominently higher in ANT39 (~80%) compared to TN11 callus (0%). Levels of
      glucose, sucrose, and starch are all significant higher in ANT39 than in TN11
      either at callus induction or early shoot organogenesis stage. Moreover, high
      expression levels of Cell wall-bound invertase 1, Sucrose transporter 1 (OsSUT1)
      and OsSUT2 are detected in ANT39 at the fourth-day in CIM but it cannot be
      detected in TN11 until the tenth-day. It suggested that ANT39 has higher callus
      growth rate and shoot regeneration ability may cause from higher activity of
      sucrose uptake and metabolism. As well, the expression levels of ORYZA SATIVA
      RESPONSE REGULATOR 1 (ORR1), PIN-formed 1 and Late embryogenesis-abundant 1,
      representing endogenous cytokinin, auxin and ABA signals, respectively, were also
      up-regulated in highly regenerable callus, ANT39, but only ORR1 was greatly
      enhanced in TN11 at the tenth-day in CIM. CONCLUSION: Thus, phytohormone signals
      may affect sucrose metabolism to trigger callus initiation and further de novo
      shoot regeneration in rice culture.

PMID- 28510849
TI  - Inhibitory activities of acteoside, isoacteoside, and its structural constituents
      against protein glycation in vitro.
AB  - BACKGROUND: Advanced glycation end products (AGE) are substances that can induce
      insulin resistance in adipocyte, hepatocyte and muscle cells. This resistance
      correlates highly with cardiovascular disease and diabetic complications.
      Acteoside (A), a phenylethanoid glycoside, is an active compound in several
      plants and traditional herbal medicines. Acteoside, its structural isomer,
      isoacteoside (I), and their constituents, caffeic acid (C) and 3,4
      dihydroxyphenylethanol (D), were used in the study to investigate the inhibitory
      activity against AGE formations in vitro. RESULTS: AGE formations were detected
      by anti-(Nepsilon-(carboxymethyl)lysine (anti-CML), using bovine serum albumin
      (BSA)/glucose (glc) and BSA/galactose (gal) as models, or by anti-argpyrimidine
      (anti-AP), using BSA/methylglyoxal (MGO) as models. It was found that A, I, C, or
      D, each at 5 mM, could attenuate the CML formations detected by ELISA in the
      BSA/gal model of a 3-day or 5-day reaction, and showed significant differences (P
      < 0.01 or P < 0.001) compared to the control. However, these compounds showed a
      minor effect after a 7-day incubation. It was also found that C or D could lower
      the CML formations in the BSA/glc model and showed significant differences (P <
      0.05 or P < 0.01) compared to the control after a 3-day, 5-day and 7-day
      reaction. It was found that A, I, C, or D, each at 0.5 mM or 5 mM, could
      attenuate the AP formations in the BSA/MGO model of a 3-day reaction and showed
      significant differences (P < 0.001) compared to the control. CONCLUSIONS: The
      results suggest the potential anti-glycation activities of A and I in vitro may
      apply to cell models at higher glucose concentrations or to diabetic animal
      models, and need further investigation.

PMID- 28510850
TI  - Chemical composition and tyrosinase inhibitory activity of Cinnamomum cassia
      essential oil.
AB  - BACKGROUND: Essential oils extracted from aromatic plants exhibit important
      biological activities and have become increasingly important for scientific
      research. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has
      various functional properties, however, little information is available regarding
      the tyrosinase inhibitory activity. Therefore, the objectives of this study were
      to investigate the chemical composition and tyrosinase inhibitory activity of the
      CC-EO. RESULTS: cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%)
      were found to be the two major components of the CC-EO identified by gas
      chromatography-mass spectrometry (GC-MS). The inhibitory activities of CC-EO and
      its major constituents were further evaluated against mushroom tyrosinase. The
      results showed that CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities
      with IC50 values of 6.16 +/- 0.04 mg/mL and 4.04 +/- 0.08 mg/mL, respectively.
      However, cis-2-methoxycinnamic acid did not show any anti-tyrosinase activity.
      The inhibition kinetics were analyzed by Lineweaver-Burk plots and second
      replots, which revealed that CC-EO and cinnamaldehyde were mixed-type inhibitors.
      The inhibition constants (Ki) for CC-EO and cinnamaldehyde were calculated to be
      4.71 +/- 0.09 mg/mL and 2.38 +/- 0.09 mg/mL, respectively. CONCLUSION: These
      results demonstrate that CC-EO and its major component, cinnamaldehyde, possess
      potent anti-tyrosinase activities and may be a good source for skin-whitening
      agents.

PMID- 28510851
TI  - 24-epibrassinolide restores nitrogen metabolism of pigeon pea under saline
      stress.
AB  - BACKGROUND: Several studies have shown that brassinosteroids attenuate the
      effects of salt stress. However, nothing is known about their effects on amino
      acid transport, nor the effects of these hormones on nitrate uptake under saline
      conditions. This study set out to determine the effects of 24-epibrassinolide, at
      concentrations of 10-7 M and 0.5 * 10-9 M, and clotrimazole (inhibitor of
      brassinosteroid synthesis), at 10-4 M, on nitrate uptake and metabolism in plants
      of C. cajan (L.) Millsp, cultivar C11, growing under salinity. The following
      aspects were analyzed: levels of proteins, amino acids, nitrate, nitrate
      reductase of roots and the composition of xylem sap amino acids. RESULTS:
      Salinity reduced the proportion of N-transport amino acids ASN (the major
      component), GLU, ASP and GLN. The effect of the hormone in reducing the adverse
      effects of salt was related to the reestablishment (totally or partially) of the
      proportions of GLU, ASN and GLN, transported in the xylem and to the small but
      significant increase in uptake of nitrate. Increased nitrate uptake, induced by
      24- epibrassinolide, was associated with a higher activity of nitrate reductase
      together with greater levels of free amino acids and soluble proteins in roots of
      plants cultivated under saline conditions. CONCLUSION: The decline in several
      components of nitrogen metabolism, induced by salt, was attenuated by 24
      epibrassinolide application and accentuated by clotrimazole, indicating the
      importance of brassinosteroid synthesis for plants growing under salinity.

PMID- 28510852
TI  - Synotis baoshanensis (Asteraceae), a new species from Yunnan, China.
AB  - BACKGROUND: Synotis (Asteraceae; Senecioneae) is a genus of about 55 species
      mostly distributed in the Sino-Himalayan region. During a botanical expedition in
      southwestern China in 2012, we found an unusual population of Synotis in
      southwestern Yunnan Province. To determine the taxonomic identity of the
      population, we carried out gross-morphological, floral micromorphological, and
      cytological observations. RESULTS: Our gross-morphological observations have
      shown that the population is most similar to Synotis auriculata C. Jeffrey & Y.
      L. Chen in leaf shape and in the number of phyllaries and florets, but readily
      distinguishable by the glabrous stem and petiole (vs. glandular pubescent), the
      exauriculate petiole (vs. auriculate), the uppermost leaves obviously smaller
      than the middle ones (vs. almost equally sized), and the larger ray florets (4
      4.5 mm vs. ca. 2.5 mm). The floral micromorphological observations on the
      population agree with previous reports for other species of Synotis. The
      chromosomes of the population are counted to be 2n = 40. Its karyotype is
      formulated as 2n = 20m + 14sm + 6st. CONCLUSIONS: The population was determined
      to represent a new species, i.e. Synotis baoshanensis M. Tang & Q. E. Yang, which
      is described herein. The species belongs to Synotis ser. Microglossae.

PMID- 28510853
TI  - Leucaena leucocephala leachate compromised membrane integrity, respiration and
      antioxidative defence of water hyacinth leaf tissues.
AB  - BACKGROUND: Water hyacinth is an invasive aquatic weed in many regions of the
      world. In this study, the bioherbicidal potential of allelopathic plant Leucaena
      leucocephala against water hyacinth was investigated using a leaf disc assay.
      RESULTS: L. leucocephala leachate enhanced electrolyte leakage from water
      hyacinth leaf discs in a concentration-dependent manner. Control experiments
      eliminated the possibilities that increased membrane permeability in the leachate
      treated leaf discs was due to pH or osmotic effects of the leachate. Thus, the
      loss of membrane stability in the leachate-treated leaf discs was likely due to
      phytotoxins detected in the leachate, namely mimosine and phenolic constituents.
      Decline in tissue respiration was detected in leachate-treated water hyacinth
      leaf discs. This suggests that the L. leucocephala leachate may contain compounds
      which acted as respiratory inhibitors. Enhanced reactive oxygen species
      production coincided with inhibition of catalase and ascorbate peroxidase
      activities in the leachate-treated water hyacinth leaf tissues. The injurious
      effects of L. leucocephala leachate on water hyacinth leaf discs probably
      involved direct inhibition of antioxidant enzymes in addition to direct
      involvement of some allelochemicals in reactive oxygen species formation.
      CONCLUSION: In summary, the toxic effects of L. leucocephala leachate on water
      hyacinth leaf discs likely lay in its ability to effectively compromise the
      membrane integrity, tissue respiration and antioxidant defence of the latter.

PMID- 28510854
TI  - Dehydroascorbate reductase and monodehydroascorbate reductase activities of two
      metallothionein-like proteins from sweet potato (Ipomoea batatas [L.] Lam.
      'Tainong 57') storage roots.
AB  - BACKGROUND: Metallothionein (MT) is a group of proteins with low molecular masses
      and high cysteine contents, and it is classified into different types, which
      generally contains two domains with typical amino acid sequences. RESULTS: In
      this report, two full-length cDNAs (MT-1 and MT-II) encoding MT-like proteins
      were isolated from the roots of sweet potato (Ipomoea batatas [L.] Lam. 'Tainong
      57'). Their open reading frames contained 642 and 519 nucleotides (66 and 81
      amino acids) for MT-1 and MT-II, respectively, and exhibited a relatively low
      amino acid sequence similarity. On the basis of the amino acid sequence
      similarity and conserved residues, it is suggested that MT-I is a member of the
      plant MT Type-I family, and MT-II is a member of the plant MT Type-II family. The
      corresponding mRNA levels of MT-1 and MT-II were the highest found in the storage
      roots. Recombinant MT-1 and MT-II protein overproduced in E. coli (M15) was
      purified by Ni2+-chelated affinity chromatography. MT-1 and MT-II reduced
      dehydroascorbate (DHA) in the presence of glutathione (GSH) to regenerate L
      ascorbic acid (AsA). However, without GSH, MT-1 and MT-II has very low DHA
      reductase activity. And AsA was oxidized by AsA oxidase to generate
      monodehydroascorbate (MDA) free radical. MDA was also reduced by MT-1 and MT-II
      to AsA in the presence of NADH mimicking the MDA reductase catalyzed reaction.
      CONCLUSIONS: These data suggest that MT-1 and MT-II have both DHA reductase and
      MDA reductase activities. MT-1 and MT-II are apparently the first reported plant
      MTs exhibiting both DHA and MDA activities in vitro.

PMID- 28510855
TI  - Phenology and pollinating wasp dynamics of Ficus microcarpa L.f.: adaptation to
      seasonality.
AB  - BACKGROUND: In the obligate plant/pollinator mutualism, pollinator abundance is
      conditioned by the host resource. In order to investigate the population
      fluctuation of pollinating wasps and the phenological processes involved, this
      study examined the dual dynamics of the pollinator and the syconium phenology of
      a seasonal fruited fig tree population, Ficus microparpa, in Taipei, Taiwan.
      RESULTS: Our results revealed three seasons in the annual phenology: spring crop,
      summer-fall crop and winter trough seasons. The syconium quantity was correlated
      most significantly with temperature based on the generalized linear model with
      the meteorological data transformed by a principal component analysis. The
      pollinator population showed an increasing trend in spring, reached the maximum
      abundance in summer, and then declined drastically in winter, consistent with the
      syconium production fluctuation. With the small amount of local pollinators from
      the winter syconia and potential immigrating foundresses from other populations,
      the pollinator population size can increase very quickly from almost zero to over
      40,000 wasps for this 29-tree local population within a season. CONCLUSION: This
      syconium phenological scheme, coupled with the fast-recovery rate of pollinators,
      may explain the worldwide adaptation and invasion of Ficus microcarpa.

PMID- 28510856
TI  - Morphological and molecular characteristics of Homoeostrichus formosana sp. nov.
      (Dictyotaceae, Phaeophyceae) from Taiwan.
AB  - BACKGROUND: In the marine brown macroalgae, the morphological characters are
      highly similar between two widely distributed genera, Homoeostrichus and Zonaria
      (Dictyotaceae), thereby resulting in the difficulty of exploring their hidden
      biodiversity. Owing to the help of the molecular tools, it is now easy for
      scientists to objectively describe a new species in nature. In this study, we
      make a description on the Homoeostrichus formosana sp. nov. from Taiwan, Indo
      Pacific Ocean based on the morphological evidence and molecular data. RESULTS:
      Our morphological observations revealed that this species has marginal row of
      apical cells responsible for thallus growth and the thallus with four layers of
      cells except the marginal regions. The cortical cell lies upon each medullary
      cell in transverse section, and two cortical cells upon each medullary cell in
      longitudinal section. Tetrasporangium is developed from cortical cell with stalk
      cell and singly scattered over the thallus surface, and has no indusia and
      paraphyses. Molecularly, the phylogenetic trees based on SSU, psaA, psbA, and
      rbcL gene sequences supported that Homoeostrichus species are closely related to
      Exallosorus species and clearly separated from each others in addition to Zonaria
      species. CONCLUSIONS: Homoeostrichus formosana sp. nov. can now be clearly
      distinguished from E. harveyanus and Japanese H. flabellatus.

PMID- 28510857
TI  - Treeline dynamics in response to climate change in the Min Mountains,
      southwestern China.
AB  - BACKGROUND: Abies faxoniana is the dominant plant species of the forest ecosystem
      on the eastern edge of Qinghai-Tibet Plateau, where the treeline is strongly
      defined by climate. The tree-ring chronologies and age structure of Abies
      faxoniana were developed in the treeline ecotones on the northwestern and
      southeastern aspects of the Min Mountains in the Wanglang Nature Reserve to
      examine the treeline dynamics of recent decades in response to climate change.
      RESULTS: On the northwestern aspect, correlation analysis showed that the radial
      growth was significantly and positively correlated with precipitation in current
      January and monthly mean temperature in current April, but significantly and
      negatively correlated with monthly mean temperature in previous August. On the
      southeastern aspect, the radial growth was significantly negatively correlated
      with monthly mean temperature in previous July and August. CONCLUSIONS: The
      different responses of radial growth to climatic variability on both the aspects
      might be mainly due to the micro-environmental conditions. The recruitment
      benefited from the warm temperature in current April, July and September on the
      northwestern aspect. The responses of radial growth and recruitment to climatic
      variability were similar on the northwestern slope. Recruitment was greatly
      restricted by competition with dense bamboos on the southeastern aspect.

PMID- 28510858
TI  - Synotis xinningensis (Asteraceae), a new species from Hunan, China.
AB  - BACKGROUND: Synotis is one of the several genera within Senecioneae (Asteraceae)
      with more than 40 species that are mainly distributed in China or in the Sino
      Himalayan region. During a botanical expedition in central and southwestern China
      in 2011, we found an unusual population of Synotis in southwestern Hunan
      Province. To determine the taxonomic identity of the population, we carried out
      gross-morphological, floral micromorphological, and cytological observations.
      RESULTS: Our gross-morphological observations have shown that the population is
      most similar to Synotis changiana Y. L. Chen, but readily distinguishable in the
      discoid capitula (vs. radiate), and in the bracts of calyculus 9-10 (vs. 6-8), 6
      7 mm long (vs. 3-4 mm). The floral micromorphological observations on the
      population and S. changiana agree with previous reports for other species of
      Synotis. The chromosomes of the population are counted to be 2n = 40 + 0-1B. Its
      karyotype is formulated as 2n = 22m + 14sm + 4st. CONCLUSIONS: The population is
      determined to represent a new species, i.e. Synotis xinningensis M. Tang & Q. E.
      Yang, which is described herein. The new species belongs to Synotis ser. Synotis.

PMID- 28510859
TI  - Deep cytogenetics analysis reveals meiotic recombination depletion in species of
      Senecio (Asteraceae).
AB  - BACKGROUND: Senecio is the largest genus in the Asteraceae family growing in all
      environments around the world. It displays taxonomic and systematical
      difficulties. Cytogenetic knowledge of this genus is ancient, scarce and mainly
      restricted to chromosome number records. RESULTS: In this study we analyzed
      chromosome number, meiotic configuration, bivalent morphology, meiotic behavior
      and pollen grain stainability on 100 accessions of 27 different polyploid Senecio
      L. sect Senecio entities. Median, standard deviation and mode were calculated for
      number and position of chiasmata and meiotic recombination was statistically
      evaluated. Although high frequency of multivalents and associated meiotic
      irregularities are expected in high polyploids, bivalents predominance and,
      consequently, regular meiosis were observed, with normal sporogenesis and high
      pollen grain stainability. CONCLUSION: Depletion in the total chiasmata was
      significant only in some species but the terminal position was preferential in
      all the entities analyzed, indicating significant reduction in recombination. The
      regular meiosis observed suggest that intra and intergenomic reorganization
      process occur quickly and efficiently in this genus. Mechanisms of
      diploidization, common to all polyploids, are reinforced by the strong reduction
      in crossing-over rushing polyploids stabilization.

PMID- 28510860
TI  - The extent of Ds1 transposon to enrich transcriptomes and proteomes by
      exonization.
AB  - BACKGROUND: Exonization is an event which an intronic transposed element (TE)
      provides splice sites and leads to alternatively spliced cassette exons. Without
      disrupting of the inserted gene's function, TEs can expand the proteome diversity
      by adding the splice variant that encodes a different, yet functional protein.
      Previously, we found that the main contribution of Ds exonization for gene
      divergence is not providing genetic messages but incorporating the intron
      sequences with different reading frame patterns to enrich the plant proteome.
      Ds1, another member of Ac/Ds transposon system, differs from Ds by providing 3
      splice donor sites and 2 acceptor sites for alternative splicing, which may
      greatly increase the extent for proteome expansion. RESULTS: In this study, we
      performed a genome-wide survey of Ds1 exonization events to assess its extent to
      enrich proteomes in plants. Each Ds1 insertion yielded 11 transcript isoforms by
      integrating the splice donor and/or acceptor sites, which composed a bulk of all
      exonized transcript orthologs from the dicot Arabidopsis thaliana and the monocot
      Oryza sativa (rice). The exonized transcripts were analyzed by the locations of
      the termination codon (PTC) and the putative targets for the nonsense-mediated
      decay (NMD) pathway were then excluded. Compared with the Ds element, Ds1 harbors
      more contents of non-NMD transcripts for protein isoforms. CONCLUSIONS: The
      contribution of Ds1 exonization for gene divergence is incorporating the intron
      sequences with different reading frame patterns to enrich the plant proteome. All
      these simulation results direct new experimental analysis at the molecular level.

PMID- 28510862
TI  - Primulina cardaminifolia (Gesneriaceae), a rare new species from limestone areas
      in Guangxi, China.
AB  - BACKGROUND: Primulina cardaminifolia Yan Liu & W.B. Xu (Gesneriaceae), a distinct
      new species with imparipinnate leaves, is described and illustrated from a
      limestone valley in Guangxi Zhuangzu Autonomous Region, China. To assure its
      generic placement and phylogenetic affinity, phylogenetic analyses were performed
      using DNA sequences of nuclear ITS and chloroplast trnL-F intron spacer region.
      Additionally, somatic chromosome number was counted and pollen stainability was
      tested. RESULTS: Phylogenetic analyses support its placement in Primulina;
      however, two phylogenetically distinct ITS sequence types were detected,
      suggesting a probable hybrid origin. Its pollen stainability is 100% and its
      chromosome number, 2n = 36, is congruent with all known counts of diploid species
      of the genus. CONCLUSION: All available data support the recognition of the new
      species Primulina cardaminifolia and suggest that it could have derived from
      homoploid hybrid speciation. Color plates, line drawings and a distribution map
      are provided to aid in identification.

PMID- 28510861
TI  - Ectopic expression of OsMADS45 activates the upstream genes Hd3a and RFT1 at an
      early development stage causing early flowering in rice.
AB  - BACKGROUND: The rice gene, OsMADS45, which belongs to the MADS-box E class gene,
      participates in the regulation of floral development. Previous studies have
      revealed that ectopic expression of OsMADS45 induces early flowering and
      influences reduced plant height under short-day (SD) conditions. However, the
      regulation mechanism of OsMADS45 overexpression remains unknown. We introduce an
      OsMADS45 overexpression construct Ubi:OsMADS45 into TNG67 plants (an Hd1 (Heading
      date 1) and Ehd1 (Early heading date 1) defective rice cultivar grown in Taiwan),
      and we analyzed the expression patterns of various floral regulators to
      understand the regulation pathways affected by OsMADS45 expression. RESULTS: The
      transgenic rice exhibit a heading date approximately 40 days earlier than that
      observed in TNG67 plants, and transgenic rice display small plant size and low
      grain yield. OsMADS45 overexpression did not alter the oscillating rhythm of the
      examined floral regulatory genes but advanced (by approximately 20 days) the up
      regulate of two florigens, Hd3a (Heading Date 3a) and RFT1 (RICE FLOWERING LOCUS
      T1) and suppressed the expression of Hd1 at the juvenile stage. The expression
      levels of OsMADS14 and OsMADS18, which are two well-known reproductive phase
      transition markers, were also increased at early developmental stages and are
      believed to be the major regulators responsible for early flowering in OsMADS45
      overexpressing transgenic rice. OsMADS45 overexpression did not influence other
      floral regulator genes upstream of Hd1 and Ehd1, such as OsGI (OsGIGANTEA),
      Ehd2/Osld1/RID1 and OsMADS50. CONCLUSION: These results indicate that in
      transgenic rice, OsMADS45 overexpressing ectopically activates the upstream genes
      Hd3a and RFT1 at early development stage and up-regulates the expression of
      OsMADS14 and OsMADS18, which induces early flowering.

PMID- 28510863
TI  - Xiphopterella devolii (Polypodiaceae), a new species and newly recorded genus in
      Taiwan.
AB  - BACKGROUND: Grammitid ferns are a tropical monophyletic clade nested in
      Polypodiaceae, containing more than 20 genera and more than 750 species. Many of
      them also grow in Taiwan. During the survey of recent two decades, an unknown
      grammitid fern was discovered and the taxonomic treatment is given herein.
      RESULTS: A new species, collected from Taiwan, is recognized and named, i.e.,
      Xiphopterella devolii S. J. Moore, Parris, & W. L. Chiou. The holotype is
      deposited in TAIF, and isotypes are in HAST, K, L, US, and TNS. It is also
      distributed on SE & S China. The genus Xiphopterella is also a new record to
      Taiwan. CONCLUSION: A new species, Xiphopterella devolii S. J. Moore, Parris, &
      W. L. Chiou is documented herein. The Xiphopterella is a new recorded genus in
      Taiwan and is first found beyond Malesia regions.

PMID- 28510865
TI  - Asarum pubitessellatum, sp. nov. (sect. Heterotropa, Aristolochiaceae) from
      Taiwan based on morphological and palynological evidence.
AB  - BACKGROUND: Recently, we discovered an unknown Asarum from Taiwan which is
      closely related to A. crassisepalum S.F. Huang, T.H. Hsieh and T.C. Huang and A.
      taipingshanianum S.F. Huang, T.H. Hsieh and T.C. Huang by sharing a thick leaf
      blade, spreading perianth-lobes and a conical to cylindrical perianth-tube. We
      compared it with other related species and identified this plant as a new
      species. RESULTS: This new species differs distinctly from the above two related
      species by having larger plant body, shortened rhizomes and an inner surface of
      the perianth-tube that is covered with numerous simple trichomes (vs. glandular
      trichomes). The pollen tectum in this new species is perforate, which differs
      from the incomplete reticulate with small supratectate granules in A.
      crassisepalum and the compact rugulate with small supratectate granules in A.
      taipingshanianum. Furthermore, these three species are geographically separated
      from one another. CONCLUSIONS: Asarum pubitessellatum C.T. Lu & J.C. Wang, a new
      species is described and illustrated. The trichomes on the inner surface of the
      perianth-tube and pollen micromorphology were the valuable characters in the low
      level classification of Heterotropa species in Taiwan.

PMID- 28510866
TI  - Calanthe xhsinchuensis (Orchidaceae), a new natural hybrid from Taiwan.
AB  - BACKGROUND: Natural hybridization in plants is a vital mechanism of speciation.
      Calanthe arisanensis and C. sieboldii occur in the same habitat in northern
      Taiwan, where there are a number of plants whose morphologically characters are
      similar in between of these two species. In this report, a new natural hybrid,
      Calanthe species - C. xhsinchuensis Y.I. Lee putatively derived from the natural
      hybridization of C. arisanensis and C. sieboldii was described and illustrated.
      Besides, somatic chromosome number was counted. RESULTS: The morphological and
      histological data of flowers, capsules, roots and leaves of C. xhsinchuensis show
      an intermediate condition between its putative parents. The chromosome number, 2n
      = 40, is also congruent with its putative parents. Color plates and line drawings
      are provided to aid in identification. CONCLUSION: Base on the morphological
      characteristics of reproductive and vegetative organs, and the distributions of
      putative parents, it is proposed that C. xhsinchuensis is a natural hybrid
      between C. arisanensis Hayata and C. sieboldii Decaisne ex Regel.

PMID- 28510864
TI  - Galactolipid biosynthesis in flowers.
AB  - Phospholipids represent the highly conserved structural basis of biological
      membranes from bacteria to humans. However, plants and other photoautotrophic
      organisms are unique in using non-phosphorus galactolipids as primary components
      of their photosynthetic membranes. In light of the biomass of green tissues as
      compared with that of the overall plant body and the highly stacked thylakoid
      membrane structures in chloroplasts, galactolipids are the most abundant membrane
      lipids on the earth. Historically, the roles of galactolipids have been studied
      mainly in relation to photosynthesis, and recent advances in molecular biology
      with Arabidopsis and other model organisms have revealed an essential role of
      galactolipids in photosynthesis. However, these galactolipids are also abundant
      in non-photosynthetic organs, especially flowers, which suggests their distinct
      role apart from photosynthesis. The aim of this mini-review is to describe
      distinct biochemical properties of flower galactolipids and possible new roles,
      with a summary of the current understanding of galactolipid biosynthesis in
      Arabidopsis.

PMID- 28510867
TI  - Role of 5-aminolevulinic acid in the salinity stress response of the seeds and
      seedlings of the medicinal plant Cassia obtusifolia L.
AB  - BACKGROUND: Soil salinity, one of the major abiotic stresses affecting
      germination, crop growth, and productivity, is a common adverse environmental
      factor. The possibility of enhancing the salinity stress tolerance of Cassia
      obtusifolia L. seeds and seedlings by the exogenous application of 5
      aminolevulinic acid (ALA) was investigated. RESULT: To improve the salinity
      tolerance of seeds, ALA was applied in various concentrations (5, 10, 15, and 20
      mg/L). To improve the salinity tolerance of seedlings, ALA was applied in various
      concentrations (10, 25, 50, and 100 mg/L). After 10 mg/L ALA treatment,
      physiological indices of seed germination (i.e., germination vigor, germination
      rate, germination index, and vigor index) significantly improved. At 25 mg/L ALA,
      there was a significant protection against salinity stress compared with non-ALA
      treated seedlings. Chlorophyll content, total soluble sugars, free proline, and
      soluble protein contents were significantly enhanced. Increased thiobarbituric
      acid reactive species and membrane permeability levels were also inhibited with
      the ALA treatment. With the treatments of ALA, the levels of chlorophyll
      fluorescence parameters, i.e., the photochemical efficiency of photosystem II
      (Fv/Fm), photochemical efficiency (Fv'/Fm'), PSII actual photochemical efficiency
      (PhiPSII), and photochemical quench coefficient (qP), all significantly
      increased. In contrast, the non-photochemical quenching coefficient (NPQ)
      decreased. ALA treatment also enhanced the activities of superoxide dismutase,
      peroxidase, and catalase in seedling leaves. The highest salinity tolerance was
      obtained at 25 mg/L ALA treatment. CONCLUSION: The plant growth regulator ALA
      could be effectively used to protect C. obtusifolia seeds and seedlings from the
      damaging effects of salinity stress without adversely affecting plant growth.

PMID- 28510868
TI  - Immunocytochemical localization of saikosaponin-d in vegetative organs of
      Bupleurum scorzonerifolium Willd.
AB  - BACKGROUND: Saikosaponin-d (SSd) is an important active component of Bupleurum
      scorzonerifolium Willd., a traditional Chinese medicinal herb. Thus far, the
      biosynthetic pathway and biosynthetic site of saikosaponins in Bupleurum are
      largely unknown. The cellular localization of SSd will help in understanding
      saikosaponin biosynthesis and regulation. RESULTS: In this study, we characterize
      for the first time the localization of SSd in B. scorzonerifolium tissues and
      cells using histochemistry and immunoelectron microscopy. The results show that
      the saikosaponin distribution in different plant organs changes as they mature.
      The number of SSd gold particles distinctly differed among the roots, stems, and
      leaves, with the particles mainly concentrated in the roots. The gold particles
      were mainly observed in vacuoles, with a few particles in the protoplasm; hence,
      SSd is mainly stored in vacuoles. CONCLUSIONS: We speculate that saikosaponins
      are mainly synthesized via the mevalonate pathway in the protoplasm in young
      organs, and then transported to the central vacuole by the endoplasmic reticulum
      (ER) or the fusion of vacuoles, to protect plants from self-poisoning with the
      accumulation of more saikosaponins.

PMID- 28510869
TI  - DNA barcode assessment of Gracilaria salicornia (Gracilariaceae, Rhodophyta) from
      Southeast Asia.
AB  - BACKGROUND: DNA barcoding is becoming a widely applied tool for the quick and
      accurate identification of species. The evolution of the mitochondrial cytochrome
      c oxidase subunit I (COI) gene is sufficiently rapid to allow discrimination
      between closely related species and biogeographic subgroups within species.
      Gracilaria salicornia was originally described as being from Manila, the
      Philippines, and is distributed throughout Asia and the Indian Ocean. To more
      accurately define this species and its genetic diversity owing to the confusion
      of identification historically, DNA barcoding using the 5' end of the COI gene of
      the mitochondrial genome was applied to specimens collected from the Philippines,
      Malaysia, Thailand, China, and Japan, and they were compared to other gracilarian
      species. RESULTS: Within species, the COI marker yielded two clusters with
      nucleotide divergences of 0.0-1.3%. This divergence is slightly higher than the
      typical intraspecific variation for red algae. A total of eight COI haplotypes
      were found for G. salicornia, comprising the following groups: H1-H3 from the
      Philippines; H4 from Okinawa in Japan; H5-H7 from Malaysia, Thailand, and China;
      and H8 from Thailand. CONCLUSION: Although this work concentrated on a limited
      geographical region of a widespread taxon, the data shows intraspecific molecular
      divergences in G. salicornia and provides further evidence that DNA barcodes are
      useful tools for identifying species boundaries and examining biogeographical
      haplotypes for the genus Gracilaria.

PMID- 28510870
TI  - Factors affecting ozone sensitivity of tobacco Bel-W3 seedlings.
AB  - BACKGROUND: Since 1962, the tobacco variety Nicotiana tabacum cv. Bel-W3 has been
      used worldwide as an ozone (O3) bio-indicator. The use of indicator plants to
      monitor O3 pollution has proven problematic when trying to correlate the severity
      of injury to ambient O3 concentration. The aim of the present study was to study
      factors affecting the O3 sensitivity of Nicotiana tabacum cv. Bel-W3 seedlings.
      RESULTS: In chronic O3 pre-exposure tests, tobacco plants were cultured from
      seeds in charcoal-filtered air (CF) and noncharcoal-filtered ambient air (NF) for
      21 days. During these periods, the mean O3 concentrations of the CF and NF
      treatments were 5.5 +/- 0.2 and 14.7 +/- 0.4 ppb h-1, respectively (p < 0.001).
      At the end of the culturing period, no O3-induced foliar injury was observed in
      any of the plants. The O3 sensitivity of the tobacco plants was determined by
      exposing the plants to 150 ppb O3 for 8 hours in a fumigation chamber. The leaf
      injury index percentages (LII%) of indicator plants via the CF and NF treatments
      were 58.0 +/- 3.2% and 43.1 +/- 4.0%, respectively (p < 0.01). Twenty-one-day-old
      tobacco seedlings grown in NF air were used to test the effects of exposed leaves
      on O3 sensitivity. After removing the cotyledons and all true leaves, the NF
      seedlings with their apical buds intact were transferred to CF air. After another
      7 days of culturing, the newly developed leaves were approximately 1 cm in
      length. After O3 treatment, the LII% values of the newly developed leaves from
      the untreated and defoliated seedlings were 2.5 +/- 1.7% and 27.6 +/- 1.3%,
      respectively (p < 0.001). In acute O3 exposure tests, 21-day-old seedlings grown
      in CF air were fumigated with 150 ppb O3 for 8 hours in one day or for 4
      hours/day in two consecutive days. The LII% values for the two groups were 63.5
      +/- 7.4% and 20.1 +/- 4.3%, respectively (p < 0.001). CONCLUSIONS: The present
      findings suggest that plant pre-exposure to O3 is a critical factor influencing
      O3 sensitivity and that exposed leaves obtain acquired tolerance against O3
      injury later on.

PMID- 28510871
TI  - Lemon protein disulfide isomerase: cDNA cloning and biochemical characterization.
AB  - BACKGROUND: Protein disulfide isomerases (PDIs), a family of structurally related
      enzymes, aid in protein folding by catalyzing disulfide bonds formation,
      breakage, or isomerization in newly synthesized proteins and thus. RESULTS: A
      ClPDI cDNA (1828 bp, GenBank accession HM641784) encoding a putative PDI from
      Citrus limonum was cloned by polymerase chain reaction (PCR). The DNA sequence
      encodes a protein of 500 amino acids with a calculated molecular mass of 60.5
      kDa. The deduced amino acid sequence is conserved among the reported PDIs. A 3-D
      structural model of the ClPDI has been created based on the known crystal
      structure of Homo sapiens (PDB ID: 3F8U_A). The enzyme has two putative active
      sites comprising the redox-active disulfides between residues 60-63 and 405-408
      (motif CGHC). To further characterize the ClPDI, the coding region was subcloned
      into an expression vector pET-20b (+), transformed into E. coli Rosetta
      (DE3)pLysS, and recombinant protein expressed. The recombinant ClPDI was purified
      by a nickel Sepharose column. PDI's activity was assayed based on the ability of
      the enzyme to isomerize scrambled RNase A (sRNase A) to active enzyme. The KM,
      kcat and kcat/KM values were 8.3 * 10-3 MUM, 3.0 * 10-5 min-1, and 3.6 * 10-1 min
      1 mM-1. The enzyme was most active at pH 8. CONCLUSIONS: The advantage of this
      enzyme over the PDI from all other sources is its low KM. The potential
      applications of this PDI in health and beauty may worth pursuing.

PMID- 28510872
TI  - Improving initial infectivity of the Turnip mosaic virus (TuMV) infectious clone
      by an mini binary vector via agro-infiltration.
AB  - BACKGROUND: The in vivo infectious clone of Turnip mosaic virus (TuMV), p35S
      TuMV, was used on plant pathology research for many years. To activate p35S-TuMV,
      the plasmid was mechanically introduced to the local lesion host Chenopodium
      quinoa. However, low infectivity occurred when the TuMV from C. quinoa was
      transferred to the systemic host Nicotiana benthamiana. RESULTS: To increase the
      efficiency of initial infectivity on N. benthamiana, the expression of the TuMV
      infectious clone by a binary vector that directly activates viral RNA through
      agro-infiltration is considered to be a good alternative. The size of the binary
      vector by agro-infiltration is usually large and its backbone has numerous
      restriction sites that increase difficulty for construction. In this study, we
      attempted to construct a mini binary vector (pBD003) with less restriction sites.
      The full-length cDNA of TuMV genome, with or without green fluorescence protein,
      was inserted in pBD003 to generate pBD-TuMV constructs, which were then
      individually introduced to N. benthamiana plants by agro-infiltration. Symptom
      development and ELISA positivity with TuMV antiserum indicated that the pBD-TuMV
      constructs are infectious. Moreover, the initial infectivity of a mild strain
      TuMV-GK, which contains an R182K mutation on HC-Pro, constructed in the pBD003
      vector was significantly increased by agro-infiltration. CONCLUSION: Thus, we
      concluded that the newly constructed mini binary vector provides a more feasible
      tool for TuMV researches in areas, such as creating a mild strain for cross
      protection, or a viral vector for foreign gene expression. In addition, the
      multiple cloning sites will be further cloned in pBD003 for convenience in
      constructing other viral infectious clones.

PMID- 28510873
TI  - Enhanced tolerance of transgenic potato plants expressing choline oxidase in
      chloroplasts against water stress.
AB  - BACKGROUND: Glycinebetaine, whose biosynthesis could be catalyzed by choline
      oxidase (COD), is an extremely efficient compatible solute for scavenging
      oxidative stress-inducing molecules and protecting the photosynthetic system in
      plants. To study the effects of the codA transgene for choline oxidase on the
      drought resistance and recovery, a transgenic potato cultivar (SC) bearing codA
      gene and a non-transgenic (NT) control cultivar were raised in pots under
      moderate and severe drought stress. The experiment was constituted by a two-day
      pretreatment with 20% PEG and a four-day-water stress combined with two-day
      recovery treatment. RESULTS: Under the four-day-water stress, plants were
      provided with normal water condition, 10% or 20% polyethylene glycol. The results
      of pretreatment showed an expression of codA gene in transgenic potato and an
      accumulation of glycine betaine (GB); leaf water potential was higher in SC than
      in NT. In the stress-recovery-treatment, SC showed stronger antioxidant ability,
      more efficient photosynthetic system, higher chlorophyll content, lower
      malondialdehyde content and better recovery from water deficit stress than NT.
      CONCLUSION: Although this work concentrated on the short-term water stress and
      recover treatments on transgenic potato plants with the over-expression of CodA
      gene and its control line. The datas shows that the exogenous codA gene provided
      potato a stronger drought resistance and recovery ability.

PMID- 28510874
TI  - The NPR1 ortholog PhaNPR1 is required for the induction of PhaPR1 in Phalaenopsis
      aphrodite.
AB  - BACKGROUND: Systematic acquired resistance (SAR) is an effective broad-spectrum
      defense mechanism that confers long-lasting protection against biotrophic
      pathogens trough defense related salicylic acid (SA) signaling. Gene(s) involved
      in SAR have been extensively studied in dicot plants; however, remains largely
      unresolved in monocot plants. NPR1, an evolutionary conserved gene, plays a
      central role in SAR, and PR-1 is widely used as a marker for effective SA
      signaling. RESULTS: We identified NPR1 and PR-1 homologous genes, PhaNPR1 and
      PhaPR1, from an economically important orchid, Phalaenopsis aphrodite, and
      characterized their roles in SA signaling and Cymbidium mosaic virus (CymMV)
      resistance. A phylogenetic analysis of NPR1 homologs showed that these genes
      appear to have evolved before angiospermy. Similar to Arabidopsis NPR1, PhaNPR1
      was only moderately induced upon SA treatment and CymMV infection. Although
      PhaPR1 shows only 36% identity with AtPR1, its promoter shared conserved elements
      with those of other PR-1 genes, and it was induced upon SA treatment and CymMV
      infection. After CymMV infection, silencing on PhaNPR1 also reduced PhaPR1
      expression; however, CymMV accumulation was not affected. CONCLUSIONS: In
      conclusion, after virus infection, PhaNPR1 is required for PhaPR1 induction, but
      plays little role in defense against CymMV.

PMID- 28510875
TI  - Morphological, anatomical and physiological leaf traits of Q. ilex, P. latifolia,
      P. lentiscus, and M. communis and their response to Mediterranean climate stress
      factors.
AB  - BACKGROUND: Limitations to plant growth imposed by the Mediterranean climate are
      mainly due to carbon balance in response to stress factors. In particular, water
      stress associated to high air temperature and irradiance in summer causes a
      marked decrease in CO2 assimilation. Air temperature sensitivity of
      photosynthesis (PN) differs from that of leaf respiration (RD). PN often
      decreases sharply at temperature above its optimum while RD increases
      exponentially over short term rises in temperature. Nevertheless, the impact of
      water deficit on RD is still far from clear with reports in literature including
      decreases, maintenance or increases in its rates. The ratio RD/PN can be
      considered a simple approach to leaf carbon balance because it indicates the
      percentage of photosynthates that is respired. RESULTS: The results underline
      different morphological, anatomical and physiological traits of the evergreen
      species co-occurring in the Mediterranean maquis which are indicative of their
      adaptive capability to Mediterranean stress factors. The ratio RD/PN varies from
      0.15 +/- 0.04 in autumn, 0.24 +/- 0.05 in spring through 0.29 +/- 0.15 in winter
      to 0.46 +/- 0.11 in summer. The lower RD/PN in autumn and spring underlines the
      highest PN rates during the favorable periods when resources are not limited and
      leaves take in roughly three to five times more CO2 than they lose by
      respiration. On the contrary, the highest RD/PN ratio in summer underlines the
      lowest sensitivity of respiration to drought. Among the considered species,
      Quercus ilex and Pistacia lentiscus have the largest tolerance to low winter
      temperatures while Phillyrea latifolia and Myrtus communis to drought, and
      Phillyrea latifolia the highest recovery capability after the first rainfall
      following drought. CONCLUSIONS: The Mediterranean evergreen specie shows a
      different tolerance to Mediterranean climate stress factors. The predicted global
      warming might differently affect carbon balance of the considered species, with a
      possible change in Mediterranean shrublands composition in the long-term.
      Understanding the carbon balance of plants in water limited environments is
      crucial in order to make informed land management decisions. Moreover, our
      results underline the importance of including seasonal variations of
      photosynthesis and respiration in carbon balance models.

PMID- 28510877
TI  - Recircumscription of Begonia sect. Baryandra (Begoniaceae): evidence from
      molecular data.
AB  - BACKGROUND: Begonia sect. Diploclinium is a 'dust-bin' section for species
      retaining pleisiomorphic characters and lacking novel synapomorphic characters
      used to delimit other Asian sections in Begonia. Part of this large and
      polymorphous section is transferred to Begonia sect. Baryandra in a move towards
      a more natural classification for the genus. RESULTS: Phylogenetic analysis of
      nuclear ribosomal ITS DNA sequences show a strongly supported monophyletic group
      containing Philippine and Bornean species previously in Begonia sect.
      Diploclinium, and the type of Begonia sect. Baryandra, B. oxysperma. This clade
      forms the basis for the now much-expanded Begonia sect. Baryandra, which as
      defined here contains 49 species and has its centre of diversity in the
      Philippines. CONCLUSIONS: A natural classification for a much expanded Begonia
      sect. Baryandra has been provided. This paper highlights the feasibility of
      moving towards a natural classification of Asian Begonia step by step as
      information comes to light through building upon previous framework phylogenies
      with denser sampling.

PMID- 28510876
TI  - Antimicrobial activities of stearidonic and gamma-linolenic acids from the green
      seaweed Enteromorpha linza against several oral pathogenic bacteria.
AB  - BACKGROUND: We found that the edible green seaweed Enteromorpha linza displayed
      potent antimicrobial activity against Prevotella intermedia and Porphyromonas
      gingivalis. To elucidate the active component of E. linza, isolation procedures
      were performed. RESULTS: The main active compound was isolated by polarity
      fractionation, Sephadex LH-20 gel chromatography, and reverse-phase high
      performance liquid chromatography (RP-HPLC). The active compounds were eluted at
      isocratic 95% acetonitrile by RP-HPLC and identified as unsaturated fatty acids,
      stearidonic acid (SA, C18:4 n-3) and gamma-linolenic acid (GLA, C18:3 n-6) by gas
      chromatography-mass spectrometry, 1H nuclear magnetic resonance (NMR)
      spectroscopy, and 13C NMR spectroscopy. The yields of SA and GLA from dried
      seaweed tissue were 6.33 * 10-3% and 6.47 * 10-3%, respectively. The minimal
      inhibitory concentration values of SA and GLA were 39.06 MUg/mL against P.
      intermedia and 9.76 MUg/mL against P. gingivalis, respectively. SA and GLA were
      also active against several other oral pathogens, including Aggregatibacter
      actinomycetemcomitans, Candida albicans, Fusobacterium nucleatum subsp. vincenti,
      and Streptococcus mutans, at micromolar concentrations. CONCLUSIONS: These data
      suggest that the E. linza extracts SA and GLA are useful antimicrobial agents for
      the prevention and/or treatment of periodontitis.

PMID- 28510879
TI  - Cryopreservation the seeds of a Taiwanese terrestrial orchid, Bletilla formosana
      (Hayata) Schltr. by vitrification.
AB  - BACKGROUND: The cryopreservation of orchid seeds is an important conservation
      method, studies of the effects of cryopreservation on the seeds of wild orchids
      are scant. This investigation was to establish a method for the vitrification and
      cryopreservation of seeds of B. formosana that may be suitable for the long term
      storage of Taiwan native orchid germplasm for conservation purposes. RESULTS: The
      germination rate and morphological stability of seeds from spontaneous-dehiscent
      capsules of Bletilla formosana (Hayata) Schltr. were evaluated after
      cryopreservation by vitrification. The germination rates of cryopreserved seeds
      varied according to immersion time and the vitrification method used. Seeds that
      were dehydrated by immersion in loading solution (LS; 2.0 M glycerol, 0.4 M
      sucrose) for 10 min to 30 min then transferred to plant vitrification solution 2
      (PVS2) for 30 min prior to freezing in liquid nitrogen (LN) showed significantly
      higher germination rates than seeds immersed in PVS2 only. The optimal immersion
      times were 10 min for LS and 30 min for PVS2, resulting in an in vitro
      germination rate of 91%. Germination was not observed for cryopreserved seeds
      that were dehydrated by immersion in LS only. Seed viabilities and germination
      rates did not vary significantly for cryostorage times from 10 minutes to 1 year.
      CONCLUSIONS: This study improve, an efficient protocol was established that
      maintained seed viability and enhanced the germination rates of seeds, compared
      with previously described cryopreservation methods, and the germinated seeds
      showed normal morphology of both vegetative and reproductive organs.

PMID- 28510878
TI  - Activation tagging in Salvia miltiorrhiza can cause increased leaf size and
      accumulation of tanshinone I and IIA in its roots.
AB  - BACKGROUND: Salvia miltiorrhiza Bunge (Danshen), an important herb in traditional
      Chinese medicine, is commonly used for treatment of cardiovascular diseases. One
      of the major bioactive constituents of Danshen, diterpenoid tanshinone, has been
      proved with pharmacological properties and have the potential to be a new drug
      candidate against various diseases. In our previous study, we have established an
      activation tagging mutagenesis (ATM) population of callus lines of S.
      miltiorrhiza Bunge by Agrobacterium- mediated transformation. RESULTS: In the
      present study, we have identified ATM transgenic Salvia plant (SH41) with
      different leaf morphology and more tanshinones in its roots. The transgenic
      background of SH41 was identified by PCR (using hpt II primers) and Southern
      blots. PCR analysis showed a single band of hpt II gene and Southern blot
      analysis showed single insertion in SH41. External appearance of ATM transgenic
      SH41 was observed with broader leaves comparing to non-transformed plants. More
      healthy trichomes as well as bigger and wobbly guard cells and stomata were
      observed in SH41 by scanning electron microscopy (SEM). Quantitative analysis of
      active compounds in SH41 roots revealed a significant increase in tanshinone I
      (3.7 fold) and tanshinone IIA (2 fold) contents as compared to the wild plant.
      CONCLUSIONS: We have generated an activation tagged transgenic Salvia plant
      (SH41) with different leaf morphology and high diterpenes content in its roots.
      The increased amount of tanshinones in SH41 will definitely offer a route for
      maximizing the benefits of this plant in traditional Chinese herbal medicines.
      The present report may also facilitate the application of ATM for genetic
      manipulation of other medicinal crops and subsequent improved metabolite
      contents.

PMID- 28510880
TI  - Biodiversity of soil algae in the farmlands of mid-Taiwan.
AB  - BACKGROUND: Very little information is available about soil algae in Taiwan. In
      this study, we investigated for the first time the soil algae inhabiting five
      types of farmland in mid-Taiwan: rice paddies, vegetable farms, tea plantations,
      sugar cane farms, and orchards. RESULTS: Sixty-four taxa belonging to 33 genera
      of cyanobacteria, diatoms, green algae, and euglenoids were identified on the
      basis of fine structures observed under optical and electron microscopes and rDNA
      sequencing. The majority of the isolates were of the genera Oscillatoria,
      Navicula, Nitzschia, and Pinnularia. Five species were reported for the first
      time in Taiwan, namely Microcoleus paludosus, M. subtorulosus, Navicula
      subminuscula, Nitzschia levidensis, and Ni. pusilla. CONCLUSIONS: The
      distribution and diversity of these species was shown to be strongly dependent on
      habitat, with the highest diversity of green algae in the orchards, a fairly high
      diversity of diatoms and cyanobacteria in the rice paddies, and a relatively low
      diversity in the tea plantations and sugar cane farms. The humidity and acidity
      were the most important environmental factors influencing the diversity of soil
      algae in these farmlands.

PMID- 28510881
TI  - Structural and functional alterations in photosynthetic apparatus of plants under
      cadmium stress.
AB  - Cadmium is a potentially toxic heavy metal that hampers plant productivity by
      interfering with their photochemistry. Cd causes disturbances in a range of
      physiological processes of plants such as photosynthesis, water relations, ion
      metabolism and mineral uptake. Cd pronouncedly affects photosynthesis by
      alteration of its vital machinery in all aspects. Photosynthesis is a well
      organised and sequential process fundamental to all green plants and
      microorganisms which involves various components, including photosynthetic
      pigments and photosystems, the electron transport system and CO2 reduction
      pathways. Any damage at any level caused by Cd, critically affects overall
      photosynthetic capacity. Present review focuses on key effects of Cd on
      photosynthetic apparatus including chloroplast structure, photosynthetic
      pigments, Chl-protein complexes and photosystems resulting in overall decrease in
      efficiency of carbon assimilation pathway.

PMID- 28510882
TI  - Characterization of differential expression and leader intron function of
      Arabidopsis atTOC159 homologous genes by transgenic plants.
AB  - BACKGROUND: Accurate import of thousands of nuclear-encoded proteins is an
      important step in plastid biogenesis. However, the import machinery of cytosolic
      precursor proteins to plastids relies on the Toc and Tic (translocons on the
      outer envelope and inner envelope membrane of chloroplasts) complexes. Toc159
      protein was identified in pea (Pisum sativum) as a major receptor for the
      precursor proteins. In Arabidopsis thaliana, four psToc159 homologs are
      identified, termed atToc159, atToc132, atToc120 and atToc90. The expression of
      these protein-encoding genes has to be properly regulated, because their gene
      products must be correctly integrated to appropriate apparatus to perform their
      functions. RESULTS: In order to elucidate the regulatory mechanisms of atTOC159
      homologous gene expression, transgenes containing various lengths of the upstream
      regulatory sequences of atTOC159/atTOC132/atTOC120/atTOC90 and GUS coding
      sequence were transferred to wild type Arabidopsis. In accordance with the
      analysis of GUS activity in these transgenic plants at various developmental
      stages, these homologous genes had distinct expression patterns. AtTOC159 and
      atTOC90 are preferentially expressed in above-ground tissues, such as cotyledons
      and leaves. In mature roots, atTOC159 and atTOC132 are expressed at higher
      levels, while atTOC120 and atTOC90 are expressed at the basal level. All four
      genes have increased expression level during flower and fruit development,
      particularly a remarkably high expression level of atTOC159 in later stage of
      fruit development. Furthermore, leader intron in the 5' UTR induces the
      expression level of atTOC159 members in a tissue-specific manner. This is able to
      up-regulate the atTOC120 expression in roots/leaves/flowers, and the atTOC90
      expression in cotyledons/leaves/anthers. CONCLUSIONS: The differential expression
      of atTOC159 gene members is essential during plastid development, because proper
      atToc159 isoforms are required to import distinct proteins to the plastids of
      different tissues.

PMID- 28510883
TI  - Tissue culture-induced somaclonal variation of decreased pollen viability in
      torenia (Torenia fournieri Lind.).
AB  - BACKGROUND: Phenotypic and genotypic variations, collectively called somaclonal
      variations, are induced during tissue culture. RESULTS: We studied the phenotypic
      variation in pollen viability of regenerants of torenia after subculturing for
      one to nine generations. We found that pollen viability of regenerants
      continuously decreased with increasing subculture time. High concentrations of
      plant growth regulators applied to the Murashige and Skoog (MS) medium also
      resulted in diminished pollen viability. Furthermore, antibiotic application
      during gene transformation also decreased pollen viability of the transformants.
      However, the process of long-term culture did not significantly change pollen
      viability. The mean methylation level of regenerants showed a 0.28% to 3.95%
      decrease in seedlings subcultured in vitro for nine generations. Moreover, when
      the ninth subcultured regenerants with reduced pollen vibility were recovered in
      soil to get seeds, the pollen viability of seed-derive plants was similar to that
      of the wild type. CONCLUSIONS: The results show that plant growth regulators,
      antibiotics, and the number of subculture generations influence somaclonal
      variations in torenia. The somaclonal variations in torenia may results from
      epigenetic changes.

PMID- 28510884
TI  - Novelties in Begonia sect. Coelocentrum: B. longgangensis and B. ferox from
      limestone areas in Guangxi, China.
AB  - BACKGROUND: The spectacular karst limestone landscape in Guangxi harbors high
      level diversity and endemism of Begonia species, especially those of sect.
      Coelocentrum. In continuation of our studies in this area, we report the
      discovery of two attractive new species from southwestern Guangxi: Begonia
      longgangensis and B. ferox. RESULTS: Begonia longgangensis resembles B. liuyanii,
      also from Longgang Nature Reserve, in the broadly ovate to suborbicular leaf
      blade, differing by the much smaller leaves, subglabrous leaf surface, pink
      flowers, dichasial cymes and the remarkably long stolons sent out from rhizomes.
      Unexpectedly, both diploid (2n = 30) and triploid counts (2n = 45) were observed
      in plants collected from the type locality. Begonia ferox probably has the most
      prominent bullate leaves for the genus. In this aspect, it is similar to B.
      nahangensis reported from northern Vietnam recently, but is readily
      distinguishable by the ovate, chartaceous leaves with an acuminate apex;
      tomentose peduncle not exceeding petioles; and the much larger stature in
      vegetative parts. A diploid count of 2n = 30 was determined for this unique new
      species. CONCLUSIONS: All available data support the recognition of the two new
      species. Begonia longgangensis has remarkably long stolons and B. ferox is
      characterized by the prominent bullate leaves. Line drawings, color plates and
      comparisons are provided to aid in identification of the novelties.

PMID- 28510885
TI  - Floral biology, breeding system and pollination ecology of an endangered tree
      Tetracentron sinense Oliv. (Trochodendraceae).
AB  - BACKGROUND: Tetracentron sinense Oliv. is an endangered tree mainly distributed
      in south-central China. The breeding system and pollination ecology of T. sinense
      are unclear. With a conservation perspective, the floral biology, breeding system
      and pollination ecology of Tetracentron sinense Oliv. were investigated, in order
      to discuss the endangered factors related to pollination, and to provide
      important information for its conservation. RESULTS: Our results revealed four
      important aspects of the reproductive biology of T. sinense. 1) T. sinense
      usually flowers by the beginning of June, and the flowering period of the
      population is about two months, and the florescence of florets lasted for 15 to
      24 days with delicate fragrance. 2) The pollen/ovule ratio is 720 +/- 28, and the
      outcrossing index is three. Artificial pollination experiments showed that T.
      sinense is self-compatible, with facultative xenogamy and no indication of
      agamospermy. 3) The pollination syndrome is ambophily, and self-pollination plays
      an important role in fruit production if wind and insect pollination is
      unavailable. 4) Insect pollinators were predominantly represented by Coleoptera,
      Diptera and Hymenoptera. Syrphid fly and bees were the main effective
      pollinators. CONCLUSIONS: The results suggested that T. sinense exhibits a mixed
      mating system, and autogamy in its breeding system may provide reproductive
      assurance for the population maintenance. During flowering and pollination in
      natural population, the decrease of population density and harsh environmental
      condition might be one of crucial reasons resulting in endanger for this species.

PMID- 28510886
TI  - Enhanced synthesis of andrographolide by Aspergillus niger and Penicillium
      expansum elicitors in cell suspension culture of Andrographis paniculata (Burm.
      f.) Nees.
AB  - BACKGROUND: Andrographis paniculata (Burm. f.) Nees is an important medicinal
      plant which has enormous applications in pharmaceutical industries. Cell
      suspension culture of Andrographis paniculata (Burm. f.) Nees. was treated with
      Aspergillus niger and Penicillium expansum elicitors to enhance the synthesis of
      andrographolide, the bioactive constituent of A. paniculata. RESULT: The
      elicitation treatment with fungal elicitors (A. niger and P. expansum) was
      observed to be most suitable for eliciting andrographolide production in the
      culture. The quantification of andrographolide was done using High Performance
      Liquid Chromatography (HPLC) technique. A. niger extract (1.5 ml with10 days
      treatment duration) revealed 6.94 fold increase in andrographolide content (132
      MUg) which was higher than the control (19 MUg). P. expansum elicitor (0.6% with
      8 days treatment duration) could reveal 6.23 fold enhancement in andrographolide
      content (81.0 MUg) over control (13 MUg). CONCLUSION: The results obtained reveal
      that the longer treatment duration is most favorable for the elicitation of
      andrographolide using both the fungal elicitors.

PMID- 28510888
TI  - Exogenous hydrogen peroxide increases dry matter production, mineral content and
      level of osmotic solutes in young maize leaves and alleviates deleterious effects
      of copper stress.
AB  - BACKGROUND: The effects of exogenously applied H2O2 on growth, water status, the
      mineral ion content (Na+, K+, Ca2+, Mg2+ and Cu2+), proline, total sugars and
      soluble proteins were assessed in leaves of maize (Zea mays L.) cultivars,
      Akpinar and Pegaso exposed to excess copper (0.5 mM). Seedlings were grown in
      equal-sizes plastic pots and irrigated with Hoagland nutrient solution containing
      H2O2 or/and copper. Different treatments taken for pot experiments were named as
      the control (C), H2O2 treatment only (H2O2), excess Cu (Cu) and, Cu stress
      combined with H2O2 pretreatment (Cu + H2O2). RESULTS: Treatment of H2O2 caused
      the increases in growth, water content, mineral concentration, proline, total
      sugar and soluble protein contents compared to the control groups in the leaves
      of both cultivars. Yet excess copper caused reductions in the growth, leaf water
      potential, Na+, K+, Ca+, Mg2+ concentrations and soluble protein levels but
      increases in proline, total soluble sugars and Cu2+ contents compared to the
      control group. Dry matter, leaf water potential and mineral content of Cu + H2O2
      group revealed a lower decrease than Cu group ones. A higher increase was also
      observed in proline and total sugar contents of Cu + H2O2 group than Cu group
      ones in both cultivars. CONCLUSIONS: These data revealed that exogenous H2O2
      might increase the dry matter production and the mineral ion distribution in
      maize seedlings. Moreover, osmotic regulation might be involved in alleviation of
      copper toxicity of maize leaves by pretreatment of H2O2.

PMID- 28510887
TI  - Chemical and pharmacological investigation of micropropagated Hygrophila
      pogonocalyx produced from leaf explants.
AB  - BACKGROUND: An optimized method for indirect shoot organogenesis from the leaf
      explants of Hygrophila pogonocalyx, a rare and endemic species in Taiwan, was
      developed to supply enough quantity of plant materials for the first chemical and
      pharmacological investigation. RESULTS: Incubation of the young leaves on
      Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (0.5 mg/l)
      and indole-3-acetic acid (0.1 mg/l) resulted in the best multiplication rate for
      organogenesis. The average number of adventitious buds per leaf was 22.8 +/- 1.9
      after 8-week culture. The adventitious buds rooted and developed into plantlets
      when cultured simply on MS medium. Using this protocol, up to 37,600 plants were
      produced from a single leaf explant in one year. From the ethanol extract of the
      leaves of this micropropagated plant, 13 compounds were isolated and identified,
      including two flavones (1, 11), four flavonols (9, 10, 12, and 13), three
      phenylethanoid glycosides (6-8), two alkylated glycosides (2-3), and two steroids
      (4-5). Of these, acteoside (7) exhibited anti-tyrosinase activity in human
      epidermal melanocytes and luteolin 7-O-beta-D-glucopyranoside (11) exhibited the
      greatest neurocytoprotective activity. CONCLUSIONS: The method, indirect shoot
      organogenesis from leaf explants of H. pogonocalyx, could be developed to supply
      enough quantity of plant materials for the chemical and pharmacological
      investigation. In the present study, the isolated active compounds may develop
      for whitening agents or treating neurodegenerative diseases in the future.

PMID- 28510889
TI  - Comparative analysis among three Taiwan-specific Gentiana species and Chinese
      medicinal plant Gentiana scabra.
AB  - BACKGROUND: The root of Gentiana scabra is commonly known as Longdan in Chinese
      herbal medicines and has been used in the treatment of inflammation, anorexia,
      indigestion and gastric infections for over 2000 years. High market demand had
      made G. scabra (GS) plants not to be the only source of Longdan in China, other
      Gentiana spp., G. triflora, G. manshurica and G. rigescens, were also recognized
      as Longdan in China now. RESULTS: In this study, we identified three Taiwan
      specific Gentiana spp., G. davidii var. formosana (GDF) and G. arisanensis (GA)
      and G. scabrida var. punctulata (GSP) that are phylogenetically different from GS
      (main source of Longdan). However, the active compounds of Longdan,
      gentiopicroside and swertiamari, were found in GSP and GDF showed higher
      antioxidant ability and free radical scavenging activities than Chinese Longdan.
      This discovery might explore the medicinal potential of GDF. Meanwhile, another
      Taiwan-specific Gentiana spp., GSP, was found to have the strongest antioxidant
      ability and free radical scavenging activities which might suggest a possible use
      of GSP as a source of natural antioxidant agents for industrial purpose.
      CONCLUSIONS: The finding of this study indicated that ITS analysis can be used to
      identify Taiwan-specific Gentiana spp. Also the Taiwan-specific Gentiana spp.
      which has strongest antioxidant and free radical scavenging activities among
      others could be a better choice for industrial purpose.

PMID- 28510891
TI  - A new name and seventeen new combinations in the Magnolia (Magnoliaceae) of China
      and Vietnam.
AB  - BACKGROUND: A new name is proposed and seventeen new combinations are made as a
      result of the previous reduction of the remaining genera of subfamily
      Magnolioideae (Magnoliaceae) into the genus Magnolia. RESULTS: The replacement
      name Magnolia fansipanensis is proposed for Manglietia crassifolia Q. N. Vu et
      al., since its transfer to Magnolia would create an illegitimate later homonym of
      the fossil name M. crassifolia Gopp. A further 17 new combinations are made to
      transfer the following taxa to Magnolia: Manglietia guangzhouensis A. Q. Dong et
      al., M. kaifui Q. W. Zeng & X. M. Hu, M. lawii N. H. Xia & W. F. Liao, plus
      Michelia concinna H. Jiang & E. D. Liu, M. jianfenglingensis G. A. Fu & K. Pan,
      M. viridipetala Y. W. Law et al., M. wuzhishangensis G. A. Fu & K. Pan, M.
      xianianhei Q. N. Vu and Yulania carnosa D. L. Fu & D. L. Zhang, Y. cuneatofolia
      T. B. Chao (probably Zhao) et al., Y. dabieshanensis T. B. Zhao et al., Y.
      dimorpha T. B. Zhao & Z. X. Chen, Y. fragarigynandria T. B. Zhao et al., Y.
      shirenshanensis D. L. Fu & T. B. Zhao, Y. shizhenii D. L. Fu & F. W. Li, Y.
      verrucata D. L. Fu et al. and Y. xinyangensis T. B. Zhao et al. CONCLUSIONS: The
      transfer of the above taxa to Magnolia is necessary following the present almost
      universal recognition of Magnolioideae as one of two monogeneric subfamilies
      within Magnoliaceae.

PMID- 28510890
TI  - Antibacterial, anti-glucosidase, and antioxidant activities of selected highland
      ferns of Malaysia.
AB  - BACKGROUND: Ferns contain natural products with potential therapeutic
      applications. Current knowledge of the pharmacological properties of ferns,
      specifically those growing at high altitudes, is limited. This study aimed to
      evaluate the phytochemical contents as well as antibacterial, anti-glucosidase,
      and antioxidant activities of four highland ferns in Malaysia. RESULTS: Aqueous
      extracts of the leaves and rhizomes of Cyathea latebrosa, Dicranopteris curranii,
      Gleichenia truncata, and Phymatopteris triloba were analysed. P. triloba leaf
      extract had the highest contents of total flavonoids (118.6 mg/g dry matter),
      hydroxycinnamic acids (69.7 mg/g dry matter), and proanthocyanidins (29.4 mg/g
      dry matter). P. triloba leaf and rhizome extracts as well as G. truncata leaf
      extract inhibited the growth of both Gram-positive and Gram-negative bacteria. P.
      triloba leaf extract produced a minimum inhibitory concentration (MIC) value of
      0.78 mg dry matter/mL when tested against Pseudomonas aeruginosa, which is 2.5
      fold higher than that of ampicillin. Among all extracts, P. triloba leaf extract
      had the highest anti-glucosidase activity (EC50 = 56 MUg dry matter/mL) and also
      the highest antioxidant potential based on DPPH radical scavenging and Ferric
      Reducing Antioxidant Power assays. Antioxidant activities of both the leaf and
      rhizome extracts correlated positively with total flavonoid and hydroxycinnamic
      acid contents (R2 = 0.80-0.95). On the other hand, anti-glucosidase activity
      correlated with total proanthocyanidin contents in both the leaf and rhizome
      extracts (R2 = 0.62-0.84). CONCLUSIONS: In conclusion, highland ferns are
      potential sources of antibacterial agents, glucosidase inhibitors, and
      antioxidants.

PMID- 28510892
TI  - Sedum tarokoense (Crassulaceae), a new species from a limestone area in Taiwan.
AB  - BACKGROUND: An unknown Sedum was found from the limestone region in Taiwan. After
      a detailed comparison with other congeners in Taiwan and neighboring countries,
      we identified this plant as a new species. RESULTS: This new taxon resembles S.
      nokoense Yamamoto, S. alfredii Hance, and S. uniflorum Hook. & Arn. subsp.
      oryzifolium (Makino) H. Ohba, but differs in leaf shape, sepal morphology, and
      seed testa micro-morphology. Ecologically, this new taxon occurs exclusively on
      limestone, while S. nokoense and S. alfredii grow in non-limestone areas and S.
      uniflorum subsp. oryzifolium is only found on sandy seashores. CONCLUSIONS: Sedum
      tarokoense H.W. Lin & J.C. Wang is described as a new species. We provide a
      description, line drawing, and distribution map, as well as photograph, a key and
      a table to distinguish S. tarokoense from its related species.

PMID- 28510893
TI  - De novo transcriptome assembly and novel microsatellite marker information in
      Capsicum annuum varieties Saengryeg 211 and Saengryeg 213.
AB  - BACKGROUND: Pepper, Capsicum annuum L., Solanaceae, is a major staple
      economically important vegetable crop worldwide. Limited functional genomics
      resources and whole genome association studies could be substantially improved
      through the application of molecular approach for the characterization of gene
      content and identification of molecular markers. The massive parallel
      pyrosequencing of two pepper varieties, the highly pungent, Saengryeg 211, and
      the non-pungent, Saengryeg 213, including de novo transcriptome assembly,
      functional annotation, and in silico discovery of potential molecular markers is
      described. We performed 454 GS-FLX Titanium sequencing of polyA-selected and
      normalized cDNA libraries generated from a single pool of transcripts obtained
      from mature fruits of two pepper varieties. RESULTS: A single 454 pyrosequencing
      run generated 361,671 and 274,269 reads totaling 164.49 and 124.60 Mb of sequence
      data (average read length of 454 nucleotides), which assembled into 23,821 and
      17,813 isotigs and 18,147 and 15,129 singletons for both varieties, respectively.
      These reads were organized into 20,352 and 15,781 'isogroups' for both varieties.
      Assembled sequences were functionally annotated based on homology to genes in
      multiple public databases and assigned with Gene Ontology (GO) terms. Sequence
      variants analyses identified a total of 3,766 and 2,431 potential (Simple
      Sequence Repeat) SSR motifs for microsatellite analysis for both varieties, where
      trinucleotide was the most common repeat unit (84%), followed by di (9.9%), hexa
      (4.1%) and pentanucleotide repeats (2.1%). GAA repeat (8.6%) was the most
      frequent repeat motif, followed by TGG (7.2%), TTC (6.5%), and CAG (6.2%).
      CONCLUSIONS: High-throughput transcriptome assembly, annotation and large scale
      of SSR marker discovery has been achieved using next generation sequencing (NGS)
      of two pepper varieties. These valuable informations for functional genomics
      resource shall help to further improve the pepper breeding efforts with respect
      to genetic linkage maps, QTL mapping and marker-assisted trait selection.

PMID- 28510894
TI  - Biomass carbon accumulation in aging Japanese cedar plantations in Xitou, central
      Taiwan.
AB  - BACKGROUND: Japanese cedar (Chrytomeria japonica D. Don) is an important
      plantation species in Taiwan and represents 10% of total plantation area. It was
      first introduced in 1910 and widely planted in the northern and central
      mountainous areas of Taiwan. However, a change in forest management from exotic
      species to native species in 1980 had resulted in few new Japanese cedar
      plantations being established. Most Japanese cedar plantations are now between 30
      and 50 years old and reaching their rotation period. It is of interest to know
      whether these plantations could be viable for future carbon sequestration through
      the accumulations of stand carbon stocks. Twelve even-aged Japanese cedar stands
      along a stand age gradient from 37 to 93 years were selected in Xitou of central
      Taiwan. The study aims were to investigate the basic stand characteristics and
      biomass carbon stock in current Japanese cedar stands, and determine the
      relationships among stand characteristics, tree biomass carbon, and stand age.
      RESULTS: Our results indicate that existing Japanese cedar plantations are still
      developing and their live tree biomass carbon continues to accumulate. At stands
      with a stand age of 90 years, tree density, canopy height, mean diameter at
      breast height, basal area, and live tree biomass carbon stocks reach to nearly
      430 tree ha-1, 27 m, 48 cm, 82 m2 ha-1 and 300 Mg C ha-1, respectively.
      CONCLUSIONS: Therefore, with no harvesting, current Japanese cedar plantations
      provide a carbon sink by storing carbon in tree biomass.

PMID- 28510896
TI  - Conspecificity of two morphologically distinct calcified red algae from the
      northwest Pacific Ocean: Galaxaura pacifica and G. filamentosa (Galaxauraceae,
      Rhodophyta).
AB  - BACKGROUND: Members of the calcified red algal genus, Galaxaura, are distributed
      predominantly in warm temperate, subtropical, and tropical regions worldwide. The
      capacity of these algae to form calcified thalli could play a critical role in
      the carbon cycle of these ecosystems. Previous studies have suggested that the
      reported species diversity of Galaxaura may be exaggerated due to a lack of
      knowledge regarding external morphological differences between gametophytic and
      tetrasporophytic plants (or among different life stages) of a single species.
      RESULTS: To examine this issue, this study collected specimens of two
      morphologically distinct Galaxaura from Taiwan and the Philippines. These
      specimens were initially identified as two species (G. pacifica Tanaka and G.
      filamentosa Chou ex Taylor) based on their morphological features. Our molecular
      analyses, however, unexpectedly showed that these two specimens shared 100%
      identical rbc L sequences, indicating that they represented a single species
      comprising two distinct external morphologies. Furthermore, our extensive
      observations and molecular analyses on several specimens from different locations
      in southern Taiwan has revealed that these morphological differences could be due
      to seasonal variation. CONCLUSIONS: This study proposes that G. "filamentosa"
      from the Philippines could represent the remnants of the lower villous part of
      older gametophytic plants of G. pacifica after senescence of the upper smooth
      part of the thallus. As such we propose that these two previously distinct algal
      species from the northwest Pacific Ocean as a single species, G. pacifica. This
      study shows that the biodiversity of the calcified red algae Galaxaura could be
      overestimated without the assistance of molecular tools. Additionally, this study
      provides insights into the biodiversity and unique biology of the calcified red
      algae Galaxaura.

PMID- 28510895
TI  - Similarity and difference in vegetation structure of three desert shrub
      communities under the same temperate climate but with different microhabitats.
AB  - BACKGROUND: Community structure and species composition are closely related to
      plant diversity and ecosystem stability. To explore the similarity in vegetation
      structure of shrub communities under the same temperate climate but with
      different microhabitats, 36, 28 and 13 sampling plots in Ephedra distachya,
      Seriphidium terrae-albae and Artemisia songarica communities were selected
      respectively, during the course of three seasons (early spring, summer, autumn)
      in Gurbantunggut Desert, north-western China. The species composition, abundance,
      biomass and soil nutrients were investigated. Floristic changes were
      characterized by similarity and ordination methods. RESULTS: Two communities, E.
      distachya and S. terrae-albae, were similar in terms of soil nutrients but
      differed from the A. songarica community. Soil organic matter, nitrogen and
      biological soil crusts accounted for the differences of microhabitats. In spring
      and summer, more plant families, genera and species were recorded in E. distachya
      and S. terrae-albae communities than in the A. songarica community but in each
      community, the number of families, genera, species, herbs and life forms showed a
      consistent trend summer > spring > autumn. There were significant differences in
      absolute biomass among the three communities, but the ratio of dead biomass to
      total biomass was consistently 1:4, indicating the constant turnover rate of
      plant biomass for nutrient cycling. In each community shrubs accounted for the
      most biomass. Herbaceous biomass was negligible but the herbs contributed the
      most richness and abundance. CONCLUSIONS: The similarity in response of all three
      communities to seasonal changes in vegetation structure and biomass allocation
      demonstrate convergence although divergence is demonstrated in soil
      characteristics or microhabitats.

PMID- 28510897
TI  - Detection and identification of the phytoplasma associated with China ixeris
      (Ixeridium chinense) fasciation.
AB  - BACKGROUND: Phytoplasmas are always associated with symptoms in host plants such
      as stunting of stems, witches'-broom, yellowing of leaves, formation of sterile
      deformed flowers, virescence and phyllody. Recently also symptom of fasciation
      was reported associated with phytoplasma presence. In the present work, China
      ixeris fasciation was observed associated with phytoplasmas in Guanzhong Area,
      Shaanxi, China. RESULTS: Phytoplasma-like bodies were observed under transmission
      electron microscope in stem tissues of symptomatic samples. The 16S rRNA operon
      and tuf genes from phytoplasmas were amplified by PCR assays. Phylogenetic trees
      were calculated respectively based on sequences data of these two genes. The
      pattern of restriction fragment length polymorphism (RFLP) was generated via
      digesting the PCR products of 16S rRNA gene with eight restriction enzymes.
      CONCLUSION: The presence of phytoplasma in China ixeris exhibiting fasciation
      symptom was confirmed by the results of TEM observation and PCR testing. Based on
      sequence data, phylogeny analysis and actual restriction fragment length
      polymorphism (RFLP) analysis, the associated phytoplasma was classified as
      related to 16SrI-C subgroup. This was the first record of phytoplasmas in China
      ixeris.

PMID- 28510898
TI  - Genetic diversity in populations of Isatis glauca Aucher ex Boiss. ssp. from
      Central Anatolia in Turkey, as revealed by AFLP analysis.
AB  - BACKGROUND: Isatidae L. is a complex and systematically difficult genus in
      Brassicaceae. The genus displays great morphological polymorphism, which makes
      the classification of species and subspecies difficult as it is observed in
      Isatis glauca Aucher ex Boiss. The aim of this study is characterization of the
      genetic diversity in subspecies of Isatis glauca Aucher ex Boiss. distributed
      widely in Central Anatolia, in Turkey by using Amplified Fragment Length
      Polymorphism (AFLP) technique. RESULTS: Eight different Eco RI-Mse I primer
      combinations produced 805 AFLP loci, 793 (98.5%) of which were polymorphic in 67
      accessions representing nine different populations. The data obtained by AFLP was
      computed with using GDA (Genetic Data Analysis) and STRUCTURE (version 2.3.3)
      software programs for population genetics. The mean proportion of the polymorphic
      locus (P), the mean number of alleles (A), the number of unique alleles (U) and
      the mean value of gene diversity (He) were 0.59, 1.59, 20, and 0.23 respectively.
      The coancestry coefficient (Theta) was 0.24. The optimal number of K was
      identified as seven. The principal component analysis (PCA) explained 85.61% of
      the total genetic variation. CONCLUSION: Isatis glauca ssp. populations showed a
      high level of genetic diversity, and the AFLP analysis revealed that high
      polymorphism and differentiated subspecies could be used conveniently for
      population genetic studies. The principal coordinate analysis (PCoA) based on the
      dissimilarity matrix, the dendrogram drawn with UPGMA method and STRUCTURE
      cluster analysis distinguished the accessions successfully. The accessions formed
      distinctive population structures for populations AA, AB, E, K, and S.
      Populations AG1 and AG2 seemed to have similar genetic content, in addition, in
      both populations several hybrid individuals were observed. The accessions did not
      formed distinctive population structures for both populations AI and ANP.
      Consequently, Ankara province might be the area, where species Isatis glauca
      Aucher ex Boiss. originated.

PMID- 28510899
TI  - Rapid regeneration and ploidy stability of 'cv IR36' indica rice (Oryza Sativa.
      L) confers efficient protocol for in vitro callus organogenesis and Agrobacterium
      tumefaciens mediated transformation.
AB  - BACKGROUND: Cereal crops are the major targets for transformation mediated crop
      improvement and IR36 is an early maturing, high yielding, insect and disease
      resistant rice variety however, it is abiotic stress sensitive. Hence,
      development of an efficient and reproducible micropropagation system via somatic
      embryogenesis and Agrobacterium tumefaciens mediated transformation is
      prerequisite to develop abiotic stress tolerant IR36. Further, Genetic stability
      of analysis of plantlets through RAPD and ISSR and Ploidy level through Flow
      cytometry (FCM) measurement of 2C DNA content is necessary for future application
      of transformed IR36. RESULTS: In this study, Mature seeds inoculated on
      (Murashige and Skoog) MS medium with 11.31 MUM 2, 4-dichlorophenoxyacetic acid
      (2, 4-D) and 0.3 MUM Kinetin (Kn) had highest callus induction frequency (98%).
      The highest regeneration frequency (80%) was observed in MS + 13.28 MUM
      Benzyladenine (BA) with 8.06 MUM alpha-naphthalene acetic acid (NAA). Randomly
      Amplified Polymorphic DNA (RAPD), Inter Simple Sequence Repeat (ISSR) and Flow
      Cytometry (FCM) analysis showed no significant variation in the 2C DNA (0.81
      pg/2C) content and Ploidy level between wild type IR36 and in vitro maintained
      rice lines. Of the various OD bacterial culture, an optimum OD of 0.4 and
      inoculation duration of 10 min resulted in efficient Agrobacterium-mediated
      transformation. beta-glucuronidase activity was maximum in callus (99.05%).
      CONCLUSIONS: These results described here confirm the reliability of this
      protocol for micropropagation and delivery of desirable gene using A. tumefaciens
      into indica rice.

PMID- 28510900
TI  - High frequency microcloning of Aloe vera and their true-to-type conformity by
      molecular cytogenetic assessment of two years old field growing regenerated
      plants.
AB  - BACKGROUND: Aloe vera (L.) Burm.f is an important industrial crop, which has
      enormous application in pharmaceutical, cosmetic and food industries. Thereby,
      the demand for quality planting material of A. vera is increasing worldwide.
      Micropropagation is the widely accepted practical application of plant
      biotechnology that has gained the status of a multibillion-dollar industry
      throughout the world and this techniques can be used to meet the industrial
      demand of A. vera. Present studies aim to develop a proficient methods of high
      frequency true-to-type plantlet regeneration without intermediate callus phase
      for A. vera. RESULTS: Nodal portion of rhizomatous stem of A. vera were cultured
      on Murashige and Skoog (MS) medium (Physiol. Plant. 15:473 - 497, 1962)
      supplemented with various cytokinin and A. vera leaf gel (AvG) as organic
      supplement. Number of proliferated shoots per explant was increased along with
      the regeneration cycles and on MS medium supplemented with 2.5 mg/L 6
      benzylaminopurine and 10.0% (v/v) AvG, only 17.8 +/- 0.35 shoots per explant were
      induced on 1st regeneration cycle whereas on 3rd regeneration cycle these number
      increase to 38.5 +/- 0.44 shoots per explant on the same medium composition. AvG
      have an encouraging role to increase the proliferation rate and on 3rd
      regeneration cycle 27.6 +/- 0.53 shoot per explant induced on 2.5 mg/L BAP, but
      these number increase to 38.5 +/- 0.44 shoots per explant when 10.0% (v/v) AvG
      was added along with 2.5 mg/L BAP. After transfer of individual excised shoots to
      a one-third strength MS medium containing 20.0% (v/v) AvG, all the shoots formed
      whole plantlets with maximum number (9.6 +/- 0.29) of roots per shoot. 95.0% of
      the regenerated plantlets survived on poly-green house. Normal flower appeared in
      84.2% field growing micropropagated plants after 18 to 20 months of field
      transfer. Further, clonal fidelity of the two years old micropropagated plants
      was established by studying mitotic and meiotic chromosomal behavior and also
      considered the chromosome number and structural organization. There were no
      alterations in chromosome phenotypes, somatic haploid (pollen mitosis) and
      diploid chromosome count (n = 7; 2n = 14), or meiotic behavior. Randomly
      amplified polymorphic DNA analyses revealed there were no somaclonal variations
      among these regenerants. CONCLUSIONS: These results confirm the very reliable
      method for large scale production of true-to-type plantlets of A. vera, which can
      be used for commercial purpose.

PMID- 28510901
TI  - Aspidistra crassifila (Asparagaceae), a new species from Guangxi, China.
AB  - BACKGROUND: Aspidistra crassifila Yan Liu & C.-I Peng, a new species of the
      Asparagaceae from Guangxi Zhuang Autonomous Region, China, is described and
      illustrated. RESULTS: The new species is similar to A. subrotata Y. Wan & C. C.
      Huang in the perianth lobes triangular-lanceolate and horizontally spreading, but
      differs by the perianth campanulate, lobes with appendages at base, stamens 6-8
      mm long, filaments enlarged, anthers adnate to perianth tube, connectives
      extended and upcurved. The chromosome number of the new species was determined to
      be 2n = 38, and the karyotype was formulated as 2n = 22m2SC+4sm+12st. CONCLUSION:
      A careful study of the literature, herbarium specimens and living plants, both in
      the wild and in cultivation in the experimental greenhouse, support the
      recognition of the new species Aspidistra crassifila, which is described herein.
      Aspidistra crassifila is currently known only from Shiwandashan Mountains, which
      lie in southern Guangxi. A line drawing, color plates and a distribution map are
      given for the new species to aid in identification.

PMID- 28510902
TI  - In vitro growth and carbon utilization of the green-leaved orchid Dendrobium
      officinale are promoted by mycorrhizal associations.
AB  - BACKGROUND: Mycorrhizal associations play a key role in the life cycle and
      evolutionary history of orchids. All orchids grow from extremely small seeds that
      are lacking in reserves, and germination and growth into an underground
      heterotrophic, achlorophyllous stage depend upon symbiotic fungi to provide
      nutrient. However, the nutritional physiology between this symbiosis and green
      leaved orchids is still unclear. To understand further how these associations
      affect growth and carbon utilization of green orchids, the green orchids were
      inoculated with two symbiotic fungi isolated from the roots of a wild orchid
      (Dendrobium officinale) in vitro and 13C stable isotope signature experiments
      were designed to analyze carbon nutrition acquisition. RESULTS: After two months,
      both fungi had formed mycorrhizal associations with the host roots. Moreover, the
      growth rate was more rapid for the mycorrhizal seedlings than for the non
      mycorrhizal seedlings. The mycorrhizal seedlings not only absorbed more 13C from
      the substrate, but also the S3-mycorrhizal seedlings assimilated more atmospheric
      13CO2 due to significantly higher effective quantum yield of photosystem II,
      compared with the non-mycorrhizal seedlings. These results suggested that the
      green orchids could receive more C nutrition from the substrate due to symbiotic
      fungi, and photosynthesis capacity of the green D. officinale could be enhanced
      by the S3 fungus, therefore carbon nutrition acquisition also increased. As a
      result, the S1- and S3- mycorrhizal seedlings showed markedly higher biomass and
      polysaccharides contents than the non-mycorrhizal seedlings. CONCLUSIONS: These
      results improve our understanding of the mycorrhizal functioning in the green
      Dendrobium and show some potential application in the cultivation of D.
      officinale.

PMID- 28510903
TI  - Characterization of soil organic matter in perhumid natural cypress forest:
      comparison of humification in different particle-size fractions.
AB  - BACKGROUND: The Chamaecyparis forest is a valuable natural resource in eastern
      Asia. The characteristics of soil humic substances and the influence of
      environmental factors in natural Chamaecyparis forests in subtropical mountain
      regions are poorly understood. The study site of a perhumid Chamaecyparis forest
      is in the Yuanyang Lake Preserved Area in northcentral Taiwan. We collected
      samples from organic horizons (Oi, Oe and Oa) and from the surface horizon (O/A
      horizon) at the summit, footslope and lakeshore to characterize the composition
      of the soil organic matter. Samples of organic horizons were dried and ground,
      and those of the O/A horizon were passed through wet sieving for different
      particle-size fractions before analysis. The C chemical structure in the samples
      was determined with CP/MAS 13C NMR spectra. RESULTS: The ratios of alkyl-C/O
      alkyl-C and aromaticity increased with decomposition of litter from the Oi, Oe,
      to Oa horizon. The ratio of alkyl-C/O-alkyl-C also increased from coarse (> 250
      MUm) to very fine (< 2 MUm) particle fractions, which indicates increased
      humification of soil organic matter (SOM) in the fine-sized fractions. However,
      aromaticity tended to decrease with decreasing particle size, so it may not be
      useful in evaluating SOM humification of different particle-size fractions.
      CONCLUSIONS: The humification degree of the samples from O horizons and different
      particle-size fractions of the O/A horizon showed no gradient change with change
      in topography. This prevalent slow decomposition of organic matter in these
      perhumid climate conditions may narrow the difference in humification from the
      summit to lakeshore.

PMID- 28510904
TI  - Effects of abscisic acid and brassinolide on photosynthetic characteristics of
      Leymus chinensis from Songnen Plain grassland in Northeast China.
AB  - BACKGROUND: It has been well demonstrated that plant growth regulators have
      important functions in multiple physiological processes. ABA and BR play crucial
      roles in response of crops to stresses. Photosynthetic capacity of Leymus.
      chinensis treated by various concentrations of ABA and BR in combination was
      determined. Further more, the mechanisms of ABA and BR treatments and potential
      for recovery of saline-alkali grasslands were discussed. RESULTS: Abscisic acid
      (ABA) and brassinolide (BR) affected leaf gas exchange, growth and biomass of L.
      chinensis. The application of ABA and BR mixtures, especially that of 0.01 mM ABA
      and 2 * 10-4 mM BR, increased the net photosynthetic rate, stomatal conductance,
      water use efficiency, the maximum net photosynthetic rate, light-saturated rate,
      leaf respiration rate, the maximum RUBP carboxylation rate, the maximum electron
      transport rate, the maximum triose-phosphate utilization, carboxylation
      efficiency and the quantum efficiency of PSII and subsequently enhanced density,
      height and biomass in L. chinensis. We also observed reduction in the light
      compensation and saturation points following the application of ABA and BR
      treatments. CONCLUSIONS: We concluded that proper use of plant growth regulators
      can enhance the plant growth and productivity on the Songnen grassland, which is
      particularly important for the improvement of saline - alkaline grassland and the
      yield of grazing lands.

PMID- 28510906
TI  - Phylogenetic analyses of Begonia sect. Coelocentrum and allied limestone species
      of China shed light on the evolution of Sino-Vietnamese karst flora.
AB  - BACKGROUND: The picturesque limestone karsts across the Sino-Vietnamese border
      are renowned biodiversity hotspot, distinguished for extremely high endemism of
      calciphilous plants restricted to caves and cave-like microhabitats that have
      functioned as biological refugia on the otherwise harsh habitats. To understand
      evolutionary mechanisms underlying the splendid limestone flora, dated phylogeny
      is reconstructed for Asian Begonia, a species-rich genus on limestone substrates
      represented by no less than 60 species in southern China, using DNA sequences of
      nrITS and chloroplast rpL16 intron. The sampling includes 94 Begonia species
      encompassing most major Asian clades with a special emphasized on Chinese
      species. RESULTS: Except for two tuberous deciduous species and a species with
      upright stems, a majority of Sino-Vietnamese limestone Begonia (SVLB), including
      sect. Coelocentrum (19 species sampled) and five species of sect. Diploclinium,
      Leprosae, and Petermannia, are rhizomatous and grouped in a strongly supported
      and yet internally poorly resolved clade (Clade SVLB), suggesting a single
      evolutionary origin of the adaptation to limestone substrates by rhizomatous
      species, subsequent species radiation, and a strong tendency to retain their
      ancestral niche. Divergence-time estimates indicate a late Miocene
      diversification of Clade SVLB, coinciding with the onset of the East Asian
      monsoon and the period of extensive karstification in the area. CONCLUSIONS:
      Based on our phylogenetic study, Begonia sect. Coelocentrum is recircumscribed
      and expanded to include other members of the Clade SVLB (sect. Diploclinium: B.
      cavaleriei, B. pulvinifera, and B. wangii; sect. Leprosae: B. cylindrica and B.
      leprosa; sect. Petermannia: B. sinofloribunda). Because species of Clade SVLB
      have strong niche conservatism to retain in their ancestral habitats in cave-like
      microhabitats and Begonia are generally poor dispersers prone to diversify
      allopatrically, we propose that extensive and continuous karstification of the
      Sino-Vietnamese limestone region facilitated by the onset of East Asian monsoon
      since the late Miocene has been the major driving force for species accumulation
      via geographic isolation in Clade SVLB. Morphologically species of Clade SVLB
      differ mainly in vegetative traits without apparent adaptive value, suggesting
      that limestone Begonia radiation is better characterized as non-adaptive, an
      underappreciated speciation mode crucial for rapid species accumulations in
      organisms of low vagility and strong niche conservatism.

PMID- 28510907
TI  - Sex expression and inbreeding depression in progeny derived from an extraordinary
      hermaphrodite of Salix subfragilis.
AB  - BACKGROUND: An extraordinary hermaphrodite of dioecious willows provides us an
      opportunity to examine the inheritance of sex expression and the magnitude of
      inbreeding depression using a progeny assay of the hermaphrodite. RESULTS: We
      indentified 165 progeny of an open-pollinated hermaphrodite of Salix subfragilis
      as siblings selfed (Self) or crossed with another hermaphrodite (Cross_H) or a
      male (Cross_M) using microsatellite genotypes. There were more selfed progeny
      (110 in Self) than outcrossed progeny (31 in Cross_H and 24 in Cross_M),
      suggesting the absence of barriers to selfing in the maternal hermaphrodite. The
      sex ratio (female:male:hermaphrodite) of the progeny differed among the sibling
      groups (27:17:66 in Self, 3:16:12 in Cross_H and 9:8:7 in Cross_M). Nearly half
      of the selfed progeny were hermaphrodites, suggesting that an identical
      combination of parental alleles in progeny reproduced the hermaphroditism of the
      parent. We measured fitness components of growth (stem height and basal area),
      survival and fertility (pollen germination proportion, number of ovules and seed
      set). The magnitudes of inbreeding depression in growth and survival (0.29-0.70)
      were higher than those in fertility (0.00-0.16). CONCLUSIONS: The findings
      suggest a genetic basis of extraordinary hermaphroditism and substantial
      inbreeding depression in survival and growth in the dieocious S. subfragilis.

PMID- 28510905
TI  - Zoomed MRI Guided by Combined EEG/MEG Source Analysis: A Multimodal Approach for
      Optimizing Presurgical Epilepsy Work-up and its Application in a Multi-focal
      Epilepsy Patient Case Study.
AB  - In recent years, the use of source analysis based on electroencephalography (EEG)
      and magnetoencephalography (MEG) has gained considerable attention in presurgical
      epilepsy diagnosis. However, in many cases the source analysis alone is not used
      to tailor surgery unless the findings are confirmed by lesions, such as, e.g.,
      cortical malformations in MRI. For many patients, the histology of tissue
      resected from MRI negative epilepsy shows small lesions, which indicates the need
      for more sensitive MR sequences. In this paper, we describe a technique to
      maximize the synergy between combined EEG/MEG (EMEG) source analysis and high
      resolution MRI. The procedure has three main steps: (1) construction of a
      detailed and calibrated finite element head model that considers the variation of
      individual skull conductivities and white matter anisotropy, (2) EMEG source
      analysis performed on averaged interictal epileptic discharges (IED), (3) high
      resolution (0.5 mm) zoomed MR imaging, limited to small areas centered at the
      EMEG source locations. The proposed new diagnosis procedure was then applied in a
      particularly challenging case of an epilepsy patient: EMEG analysis at the peak
      of the IED coincided with a right frontal focal cortical dysplasia (FCD), which
      had been detected at standard 1 mm resolution MRI. Of higher interest, zoomed MR
      imaging (applying parallel transmission, 'ZOOMit') guided by EMEG at the spike
      onset revealed a second, fairly subtle, FCD in the left fronto-central region.
      The evaluation revealed that this second FCD, which had not been detectable with
      standard 1 mm resolution, was the trigger of the seizures.

PMID- 28510908
TI  - Correlation between DNA methylation and chronological age of Moso bamboo
      (Phyllostachys heterocycla var. pubescens).
AB  - BACKGROUND: Chronological age is the primary consideration when studying the
      physiological development, aging, and flowering of bamboo. However, it's
      difficult to determine bamboo's chronological age if the time of germination is
      unknown. To investigate the chronological age of bamboo from the genomic DNA
      methylation profile, methylation-sensitive amplification polymorphism (MSAP) was
      employed to analyze the genomic DNA methylation of Moso bamboo (Phyllostachys
      heterocycla var. pubescens) from stands of nine germination-ages, using six
      primer pairs which have previously been shown to yield methylation rates that
      reflect the age of Moso bamboo. RESULTS: The results showed that the total
      genomic DNA methylation rates in Moso bamboo at different chronological ages were
      significantly different, and the increase in genomic DNA methylation rate was
      consistent with the increase of chronological age. Six primer pairs displayed
      different genomic DNA methylation rates in Moso bamboo of nine age's group;
      however, a significantly positive correlation existed among these primer pairs.
      An integrated index was obtained by performing principal component analysis on
      the six primer pairs to represent the genomic DNA methylation levels in Moso
      bamboo of various chronological ages, and a quadratic curve between the
      chronological age and genomic DNA methylation levels was obtained. CONCLUSIONS:
      Such a relationship between DNA methylation and its chronological age may serve a
      reference for its aging study in Moso bamboo.

PMID- 28510909
TI  - Variations in osmotic adjustment and water relations of Sphaerophysa kotschyana:
      Glycine betaine, proline and choline accumulation in response to salinity.
AB  - BACKGROUND: Sphaerophysa kotschyana Boiss. is naturally distributed in overly
      salty regions. The key to the completion of the life cycles of S. kotschyana in
      harsh saline soils may be hidden in changes of its osmo-protectants, but there is
      currently no information about the interaction between osmotic adjustment and
      water relations in adaptation to saline conditions. The aim of this article was
      to determine growth, relative growth rate (RGR), relative water content (RWC),
      osmotic potential (PsiPi), photosynthetic efficiency (Fv/Fm), thiobarbituric acid
      reactive substances (TBARS) and osmo-protectant contents [proline (Pro), choline
      (Cho) and glycine betaine (GB)] in S. kotschyana leaves and roots exposed to 0,
      150 or 300 mM NaCl for 7 and 14 d (days). RESULTS: The results clearly showed
      that the reductions in growth, RWC, Fv/Fm, RGR and PsiPi were more pronounced at
      300 mM, especially after 14 d. In the same group, the highest increase in TBARS
      was recorded in roots (126%) and leaves (31%). The induction at 150 mM was not as
      high. Therefore, roots appear to be the most vulnerable part of this plant.
      Moreover, S. kotschyana was able to withstand short-term low salinity.
      CONCLUSIONS: The osmo-protectant accumulation in S. kotschyana as a salinity
      acclimation or adaptation was sufficient for toleration of low salt concentration
      (150 mM). In contrast, the plants exposed to the highest NaCl concentration (300
      mM) were not able to maintain the ability to prevent water loss because of
      further decrease in root/shoot ratio of fresh weight (FW) and dry weight (DW),
      RWC and RGR.

PMID- 28510910
TI  - Cloning of a new glutathione peroxidase gene from tea plant (Camellia sinensis)
      and expression analysis under biotic and abiotic stresses.
AB  - BACKGROUND: Tea plant, Camellia sinensis (L.) O. Kuntze, a well-known heavy metal
      hyperaccumulator, possesses a powerful tolerance to heavy metals. The heavy metal
      stresses lead to reactive oxygen species (ROS) production, and high concentration
      of ROS is harmful to plants. The glutathione peroxidase gene has positive
      function to damage induced by ROS. To understand the mechanism of tolerance to
      deferent stresses in tea plant, a new glutathione peroxidase gene of tea plant
      was cloned and its expression pattern was analyzed under abiotic and biotic
      stresses. RESULTS: A novel cDNA encoding glutathione peroxidase of tea plant
      (Camellia sinensis) was isolated by rapid amplification of cDNA ends (RACE)
      method and designated as CsGPX2 (GenBank Accession No. JQ247186). This full
      length sequence was 917 nucleotides including a 510 bp open reading frame (ORF),
      which encoded a polypeptide of 169 amino acids. The deduced amino acid sequence
      showed high homology with glutathione peroxidases of angiosperms and contained
      the characteristic conserved motifs of ILAFPCNQF and FTVKD, the highest level of
      similarity was 85% to a glutathione peroxidase from Ricinus communis (Accession
      NO. XP_002509790.1). Tissue expression pattern analysis indicated that CsGPX2
      expressed similarly in root, stem, leaf and flower of tea plant. The CsGPX2 gene
      showed strong responses to most abiotic stresses including salinity, heavy metal
      toxicity, drought, heat, plant hormones, but could not be induced by biotic
      treatment. CONCLUSIONS: The result suggested that CsGPX2 had potential function
      in protecting tea plant from peroxidative damage induced by some abiotic
      stresses.

PMID- 28510911
TI  - Karyological, morphological and phytochemical characteristics of medicinal plants
      Sophora flavescens Aiton grown from seeds collected at different localities.
AB  - BACKGROUND: Dried roots of Sophora flavescens Aiton contain many phytochemicals
      that exhibit beneficial effects on human health. This study examined and compared
      the karyological, morphological and phytochemical characteristics of three S.
      flavescens populations collected from the Danda, Hualien and Yuli of Taiwan and a
      population collected from Gansu, China. RESULTS: Karyotypes of the four
      populations were similar, with a diploid number of 2n = 18. The Hualien
      population produced more roots but with less matrine and oxymatrine contents in
      its root tissue than others. However, only the root of Danda population had a
      measurable level of naringenin. The dried root of Yuli population had greater
      ferric reducing antioxidant power and trolox equivalent antioxidant capacity than
      that of the other populations. CONCLUSIONS: Thus, the collected S. flavescens
      populations, particularly the population collected from Danda, have the potential
      to be used in breeding programs.

PMID- 28510912
TI  - Endemic Amorphophallus (Araceae) from Madagascar: a revised key, a new species
      and molecular phylogeny.
AB  - BACKGROUND: Since the revision of Amorphophallus of Madagascar (Bot Jahrb Syst
      121(1):1-17, 1999) several additional new species have been described. The recent
      discovery of another new species promted the preparation of a revised key as well
      as the description of the new species. Amorphophallus hildebrandtii, never
      restudied since its analysis by Engler in 1881, has been refound and restudied.
      Meanwhile molecular phylogenetic studies have provided new insights in the
      relationships of the endemic Madagascan species. RESULTS: The new species
      Amorphophallus perrieri is described. A new revised key to the endemic
      Amorphophallus species of Madagascar is provided. An emended description of A.
      hildebrandtii is provided. A molecular phylogeny of the endemic Madagascan
      species of Amorphophallus is provided. CONLUSIONS: The enigmatic character of a
      very short spadix in A. hildebrandtii has been confirmed, after it was thought
      for many years that it was artificially shorter in the holotype specimen than in
      nature. This was suggested by the fact that the spadix of the holotype is broken.
      The monophyletic character of the Madagascan endemic species clade remained
      unchallenged after analysis including all new species discovered recently, incl.
      the new species presented in this paper.

PMID- 28510913
TI  - Effects of foliar application of salicylic acid and nitric oxide in alleviating
      iron deficiency induced chlorosis of Arachis hypogaea L.
AB  - BACKGROUND: The aim of this experiment was to analyze the alleviation mechanism
      of exogenous salicylic acid (SA) and sodium nitroprusside (SNP, a nitric oxide
      donor) on peanut seedlings under Fe deficiency. The effects of SA and SNP on iron
      uptake and availability, ions balance and oxidant damage were studied with foliar
      application of exogenous 1.0 mM SA (SA) or 2.5 mM SNP (SNP) or 0.5 mM SA+1.25 mM
      SNP [1/2(SA+SNP)] or 1.0 mM SA+2.5 mM SNP (SA+SNP). RESULTS: The results showed
      that after 21 days treatment, the peanut seedlings growing under iron deficiency
      conditions exhibited leaf interveinal chlorosis, and this iron-deficiency induced
      symptom was prevented by foliar application of SA, SNP, 1/2 (SA+SNP), especially
      SA+SNP. The increased contents of chlorophyll and active iron, and increased Fe
      accumulation in cell organelles were observed in SA+SNP treated young leaves,
      suggesting that an improvement of iron availability in plants. Moreover, the
      improved nutrient solution pH, increased H+-ATPase activity and increased iron
      concentration in roots in SA+SNP treated plants, suggesting that SA+SNP is
      effective in modulating iron uptake. Furthermore, the increased calcium (Ca),
      magnesium (Mg) and zinc (Zn) concentrations and decreased manganese (Mn) and
      copper (Cu) concentrations in the leaves and roots of peanut indicated that
      SA+SNP stimulated the maintenance of ions disturbed by Fe deficiency. In
      addition, SA+SNP alleviated the increased accumulation of superoxide anion (O2*-)
      generation rate and malondialdehyde (MDA), and modulated the antioxidant enzymes.
      CONCLUSIONS: These results indicated that the interaction of SA and SNP promoted
      Fe uptake, translocation and activation; modulated the balance of mineral
      elements; and protected Fe deficiency induced oxidative stress. Therefore, SA and
      SNP had synergistic effects in alleviating chlorosis induced by Fe deficiency.

PMID- 28510914
TI  - A phylogenetic examination of the primary anthocyanin production pathway of the
      Plantae.
AB  - BACKGROUND: Anthocyanin pigments aid in reproduction and provide ultraviolet
      protection to land plants. We have examined the phylogenetic relationships among
      the five primary enzymes responsible for producing anthocyanin pigment in its
      three major forms. Dihydroflavonol 4-reductase (DFR), anthocyanidin synthase
      (ANS), Flavonoid 3'glucosyltransferase (F3GT), flavonoid 3'hydroxylase (F3'H),
      and flavonoid 3'5' hydroxylase (F3'5'H) are responsible for the final steps in
      anthocyanin pigment production. RESULTS: We were interested in how conserved the
      anthocyanin pathway genes may be among land plants, and evolutionarily how far
      back into the plant lineage anthocyanin production may be traced. The DFR, ANS,
      F3GT, and F3'H genes date back 450 million years to the first land plants.
      Mosses, spike mosses, and ferns express these four products, although there is no
      evidence of sequence orthologues for these genes in algae. Additionally, F3'5'H
      is not evident in organisms that predated gymnosperms. CONCLUSION: Our findings
      support the hypothesis that "blue" anthocyanin pigments did not evolve until 300
      350 mya along with the gymnosperms, although the "red" anthocyanin pigments may
      be as ancient as the mosses (~450 mya).

PMID- 28510915
TI  - Real-time measurement of phloem turgor pressure in Hevea brasiliensis with a
      modified cell pressure probe.
AB  - BACKGROUND: Although the pressure flow theory is widely accepted for the
      transport of photoassimilates in phloem sieve elements, it still requires strong
      experimental validation. One reason for that is the lack of a precise method for
      measuring the real-time phloem turgor pressure from the sink tissues, especially
      in tree trunks. RESULTS: Taking the merits of Hevea brasiliensis, a novel phloem
      turgor pressure probe based on the state of the art cell pressure probe was
      developed. Our field measurements showed that the phloem turgor pressure probe
      can sensitively measure the real-time variation of phloem turgor pressure in H.
      brasiliensis but the calculation of phloem turgor pressure with xylem tension,
      xylem sap osmotic potential and phloem sap osmotic potential will under-estimate
      it. The measured phloem turgor pressure gradient in H. brasiliensis is contrary
      to the Munch theory. The phloem turgor pressure of H. brasiliensis varied from 8
      12 bar as a consequence of water withdrawal from transpiration. Tapping could
      result in a sharp decrease of phloem turgor pressure followed by a recovery from
      8-45 min after the tapping. The recovery of phloem turgor pressure after tapping
      and its change with xylem sap flow suggest the importance of phloem water
      relationship in the phloem turgor pressure regulation. CONCLUSION: The phloem
      turgor pressure probe is a reliable technique for measuring the real-time
      variation of phloem turgor pressures in H. brasiliensis. The technique could
      probably be extended to the accurate measurement of phloem turgor pressure in
      other woody plants which is essential to test the Munch theory and to investigate
      the phloem water relationship and turgor pressure regulation.

PMID- 28510916
TI  - Reproductive biology of Pittosporum dasycaulon Miq., (Family Pittosporaceae) a
      rare medicinal tree endemic to Western Ghats.
AB  - BACKGROUND: For successful cultivation and conservation of plants a detailed
      knowledge of their reproductive biology is required. The reproductive features of
      trees are important to determine the diversity patterns and community structure
      of tropical forests. The present study on reproductive biology of Pittosporum
      dasycaulon, a rare medicinal tree, was conducted in the shola forests of Vaghamon
      hills, one of the foot hills of Southern Western Ghats of India from 2008-2011.
      RESULTS: The plant flowers profusely during February to April. Inflorescence is a
      raceme and the total number of flowers per inflorescence varies from 96-217. The
      flowers are comparatively small, hermaphrodite, short pedicellate, complete,
      zygomorphic, pentamerous, polypetalous, hypogynous and light cream in colour with
      an average length of 1.14 cm. Anthesis started at 08.30 h and the flowers were
      completely opened at approximately 09.30 h followed by anther deshiscence at
      10.00-11.30 h. The pollen grains were trizonocolpate with 45 +/- 5.6 MUm in size.
      Acetocarmine staining showed 66 +/- 6% fertile pollen at the time of anther
      dehiscence. The number of pollen grains in an anther is 5246 +/- 845 and per
      flower is 26230 +/- 1021. The stigma is wet, non-papillate, capitate and contains
      a thin film of exudates under the light microscope. The superior ovary is densely
      covered with papillate hairs and containing 3-8 ovules. The important floral
      visitors include bees and butterflies. The plant is self-incompatible and an out
      crosser. Fruit set under open-pollination was poor (24%) with 58.3% fruits having
      seeds inside. There was no fruit set in manually self pollinated flowers while
      over 57% of the cross pollinated flowers set fruits. CONCLUSIONS: Our study
      presents a detailed account on reproductive biology of this medicinal tree which
      may help in the conservation and genetic improvement of this particular taxa.

PMID- 28510917
TI  - Biochemical characterization of a functional recombinant aryl-alcohol
      dehydrogenase from Taiwanofungus camphorata.
AB  - BACKGROUND: Aryl-alcohol dehydrogenases (AADs) have been known to involve in the
      metabolism of aromatic compounds. RESULTS: One TcAAD cDNA (GenBank HQ453361)
      encoding a putative aryl-alcohol dehydrogenase (AAD) was cloned from
      Taiwanofungus camphorata. The deduced amino acid sequence is conserved among the
      reported AADs. A 3-D structural model of the TcAAD has been created based on the
      known structure of voltage-dependent potassium channels subunit beta-2 (PDB code:
      3EAU). To characterize the TcAAD, the coding region was subcloned into an
      expression vector and transformed into Saccharomyces cerevisiae. The recombinant
      His6-tagged TcAAD was overexpressed and purified by Ni affinity chromatography.
      The purified enzyme showed a band of approximately 39 kDa on a 12% SDS-PAGE. The
      molecular mass determined by MALDI-TOF is 40.58 kDa which suggests that the
      purified enzyme is a monomeric enzyme. Using veratraldehyde as a substrate, the
      KM, Vmax of TcADD was determined at pH 6.0. Using benzyl alcohol derivatives as
      substrates, the oxidizing power of TcADD via NAD+ at pH 9.6 was studied.
      CONCLUSIONS: The coding sequence of the TcAAD cDNA was introduced into an S.
      cerevisiae expression system and the active enzyme purified and characterized.
      Understanding the properties of this TcAAD will be beneficial for its potential
      in xenobiotic detoxification or production of natural flavors.

PMID- 28510918
TI  - Involvement of trehalose in hydrogen sulfide donor sodium hydrosulfide-induced
      the acquisition of heat tolerance in maize (Zea mays L.) seedlings.
AB  - BACKGROUND: Trehalose, a non-reducing disaccharide, which involves in the
      acquisition of various stress tolerance, while hydrogen sulfide (H2S) is
      considered as a cell signal molecule, but H2S-induced heat tolerance and
      involvement of trehalose in plants is still unclear. RESULTS: In present study,
      pretreatment with hydrogen sulfide donor sodium hydrosulfide (NaHS) markedly
      increased the accumulation of endogenous H2S in maize seedlings under normal
      culture conditions, which in turn improved survival percentage of maize seedlings
      and mitigated increase in electrolyte leakage and malonaldehyde (MDA)
      accumulation under heat stress. In addition, treatment with NaHS activated
      increase in the activity of trehalose-6-phosphate phosphatase (TPP) under normal
      culture conditions, followed by induced the accumulation of endogenous trehalose,
      but this accumulation was eliminated by addition of sodium citrate, an inhibitor
      of TPP. During the process of heat stress, maize seedlings treated with NaHS
      maintained higher TPP activity and trehalose content than those of control. On
      the other hand, exogenous application of trehalose also increased the content of
      endogenous trehalose in maize seedlings under normal culture conditions,
      alleviated increase in electrolyte leakage and MDA accumulation under heat
      stress, which in turn improved survival percentage of maize seedlings, and the
      heat tolerance induced by trehalose was enhanced by exogenous supplement of NaHS,
      but exogenous trehalose treatment had not significant effect on the accumulation
      of endogenous hydrogen sulfide in maize seedlings. CONCLUSION: These data suggest
      that sodium hydrosulfide pretreatment could improve heat tolerance of maize
      seedlings and this improvement may be involved in trehalose accumulation by
      activating TPP activity.

PMID- 28510919
TI  - Eliminating interference by anthocyanin in chlorophyll estimation of sweet potato
      (Ipomoea batatas L.) leaves.
AB  - BACKGROUND: Spectral reflectance was evaluated for its usefulness as a
      nondestructive estimation of chlorophyll (Chl) content from three cultivars of
      sweet potato (Ipomoea batatas L.) with green, yellow, and purple leaves grown in
      a greenhouse for 22 days. While the green and yellow leaves contain variant
      amount of photosynthetic pigments without or with little level of anthocyanins,
      the purple leaves, except large amount of photosynthetic pigments, have high
      quantity of anthocyanins. RESULTS: For green and yellow leaves, the reciprocal
      reflectance (R-1) and derived indices incorporating near infrared (NIR)
      reflectance, [(Rlambda)-1 - (RNIR)-1] and [(RNIR/Rlambda) - 1], in the green and
      red edge spectral ranges were shown to be strongly correlated (r2 = 0.8 ~ 0.9)
      with the chlorophyll content. The root mean square error (RMSE) of the
      chlorophyll content estimation using these indices was < 50 mg m-2. However, when
      purple leaves containing high levels of anthocyanins were included in the sample,
      R-1 in the green spectral range and the above-mentioned indices displayed much
      weaker correlations with the chlorophyll content. The RMSE of chlorophyll
      estimation using these indices in the green spectral range sharply increased to >
      110 mg m-2 when the sample included purple leaves. The new index, [1 -
      (Rlambda/RNIR)], was therefore inferred and developed to eliminate the distorting
      effect of anthocyanins on chlorophyll content estimation using reflectance in the
      green spectral range. For leaves with high levels of anthocyanins, the
      correlation between [1 - (Rlambda/RNIR)] and the chlorophyll content remained
      strong (r2 = 0.8 ~ 0.9) in the green spectral range, and the RMSE was minimal.
      CONCLUSION: The reflectance index, [1 - (Rlambda/RNIR)], therefore represents a
      new and useful parameter for estimating leaf chlorophyll content in leaves with
      any level of anthocyanins such as purple rice leaf.

PMID- 28510921
TI  - Begonia wuzhishanensis (sect. Diploclinium, Begoniaceae), a new species from
      Hainan Island, China.
AB  - BACKGROUND: Hainan is the largest island of the Indo-Burma Biodiversity Hotspot
      and has the best preserved and most extensive tropical forests in China. A recent
      study on distribution of endangered species in China identifies southern Hainan
      as one of eight hotspots for plant conservation in the country. In continuation
      of our studies of Asian Begonia, we report the discovery of an attractive
      undescribed species, B. wuzhishanensis C.-I Peng, X.H. Jin & S.M. Ku, from Hainan
      Island. RESULTS: Living plant of the new species, Begonia wuzhishanensis, was
      collected in 2009 and cultivated in the experimental greenhouse for morphological
      and cytological studies. It flowered consecutively in 2012 and 2013 in the
      experimental greenhouse, Academia Sinica. It was assigned to the large,
      heterogeneous sect. Diploclinium. The chromosome number of this new species was
      determined to be 2n = 26. CONCLUSIONS: A careful study of literature, herbarium
      specimens and living plants, both in the wild and in cultivation, support the
      recognition of the new species Begonia wuzhishanensis, which is described in this
      paper. Begonia wuzhishanensis is currently known only from Fanyang, Wuzhishan
      Mountain in the center of the island. A line drawing, color plate, and a
      distribution map are provided to aid in identification.

PMID- 28510920
TI  - Folium Sennae protects against hydroxyl radical-induced DNA damage via
      antioxidant mechanism: an in vitro study.
AB  - BACKGROUND: In the study, Folium Sennae (FS) was firstly extracted by various
      solvents to obtain five FS extracts. Then, five FS extracts were evaluated for
      the protective effects against *OH-induced DNA damage, antioxidant abilities in
      vitro, and chemical contents using various methods. On this basis, the
      correlation graphs between the pharmacological effects and chemical contents were
      plotted to obtain the correlation coefficients (R values). Finally, in order to
      obtain biological evidence, ethyl acetate extract of FS (EAFS) was investigated
      for the protective effect against *OH-induced MSCs (mesenchymal stem cells)
      damage using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl) assay. RESULTS: The
      pharmacological assays indicated that five FS extracts could effectively protect
      against *OH-induced DNA damage. The correlation analysis suggested that the
      average R values of total phenolics, total anthraquinones, aloe-emodin, rhein,
      and emodin were respectively 0.843, 0.833, 0.753, 0.820, and 0.784, while those
      of total sugars and total saponins were respectively 0.103 and 0.0068. The
      mechanistic analysis revealed that five FS extracts could also scavenge *OH, *O2
      , DPPH* & ABTS*+ radicals, and reduce Cu2+ to Cu+. MTT assay revealed that the
      viability of MSCs which were treated with *OH radicals has been effectively
      protected by EAFS (3 and 30 MUg/mL). CONCLUSION: On this basis, it can be
      concluded that: (i) Folium Sennae exhibits a protective effect against *OH
      induced damages to DNA and MSCs; (ii ) The effects may be attributed to
      phytophenols (especially aloe-emodin, rhein, and emodin), not sugars or saponins;
      (iii) They exert the protective action via hydrogen atom transfer (HAT) and/or
      sequential electron proton transfer (SEPT) mechanisms which make phenolic -OH
      moiety be oxidized to stable semi-quinone form; (iv) The stability of semi
      quinone form can ultimately be responsible for the protective or antioxidant
      effect of phytophenols.

PMID- 28510922
TI  - Adaptation and interaction of saxicolous crustose lichens with metals.
AB  - One of the most successful mechanisms enabling fungi to survive in extreme
      subaerial environments is by formation of mutualistic symbioses with algae and/or
      cyanobacteria as lichens. Collections, field and mineral weathering studies and
      developments in modern instrumental and analytical techniques have considerably
      advanced knowledge in understanding tolerance mechanisms to stress, environmental
      adaptation, species concepts and evolutionary processes in lichens colonising
      metalliferous habitats. This review focuses on the predominantly saxicolous,
      crustose, taxonomically notoriously challenging Acarospora sens. lat. Pioneering
      studies investigating element and substance localization in Acarospora sens. lat.
      in different geological terrains led to the discovery of novel fixation
      mechanisms, new minerals and substances associated with lichens, and new taxa and
      evolutionary lineages. Acarospora sens. lat. are generally under-represented in
      collections. Systematic sampling of Acarospora sens. lat. and other saxicolous
      lichens, in different mineralogical environments is now required, a priority
      being those occurring in extreme habitats at risk from climatic and other
      environmental changes. The potential for the discovery of new lichen and mineral
      species associated with Acarospora and other saxicolous crustose lichens, is
      high. These may represent special mechanisms to tolerate metal toxicity and other
      forms of environmental stress, including photoprotection.

PMID- 28510923
TI  - Development of STS and CAPS markers for variety identification and genetic
      diversity analysis of tea germplasm in Taiwan.
AB  - BACKGROUND: Tea (Camellia sinensis) is an important economic crop in Taiwan.
      Particularly, two major commercial types of tea (Paochong tea and Oolong tea)
      which are produced in Taiwan are famous around the world, and they must be
      manufactured with specific cultivars. Nevertheless, many elite cultivars have
      been illegally introduced to foreign countries. Because of the lower cost, large
      amount of "Taiwan-type tea" are produced and imported to Taiwan, causing a
      dramatic damage in the tea industry. It is very urgent to develop the stable,
      fast and reliable DNA markers for fingerprinting tea cultivars in Taiwan and
      protecting intellectual property rights for breeders. Furthermore, genetic
      diversity and phylogenetic relationship evaluations of tea germplasm in Taiwan
      are imperative for parental selection in the cross-breeding program and avoidance
      of genetic vulnerability. RESULTS: Two STS and 37 CAPS markers derived from
      cytoplasmic genome and ESTs of tea have been developed in this study providing a
      useful tool for distinguishing all investigated germplasm. For identifying 12
      prevailing tea cultivars in Taiwan, five core markers, including each one of
      mitochondria and chloroplast, and three nuclear markers, were developed. Based on
      principal coordinate analysis and cluster analysis, 55 tea germplasm in Taiwan
      were divided into three groups: sinensis type (C. sinensis var. sinensis),
      assamica type (C. sinensis var. assamica) and Taiwan wild species (C.
      formosensis). The result of genetic diversity analysis revealed that both
      sinensis (0.44) and assamica (0.41) types had higher genetic diversity than wild
      species (0.25). The close genetic distance between the first (Chin-Shin-Oolong)
      and the third (Shy-Jih-Chuen) prevailing cultivars was found, and many recently
      released varieties are the descents of Chin-Shin-Oolong. This implies the
      potential risk of genetic vulnerability for tea cultivation in Taiwan.
      CONCLUSIONS: We have successfully developed a tool for tea germplasm
      discrimination and genetic diversity analysis, as well as a set of core markers
      for effective identification of prevailing cultivars in Taiwan. According to the
      results of phylogenetic analysis on prevailing tea cultivars, it is necessary to
      broaden genetic diversity from wild species or plant introduction in future
      breeding programs.

PMID- 28510924
TI  - Establishment of hairy root lines and analysis of iridoids and secoiridoids in
      the medicinal plant Gentiana scabra.
AB  - BACKGROUND: Gentiana scabra is commonly known as 'Longdan' is an important herb
      in traditional Chinese medicines, commonly used for the treatment of
      inflammation, anorexia, indigestion and gastric infections. Iridoids and
      secoiridoids are main bioactive compounds which attributed to the pharmacological
      properties of this plant. The use of hairy root cultures as an excellent
      alternative for the production of pharmaceutically important metabolites in less
      time period with ensured quality of raw materials. RESULTS: An efficient hairy
      root culture system of Gentiana scabra and influence of different plant growth
      regulators (PGRs) on the production of gentiopicroside, swertiamarin and loganic
      acid constituents were described. Leaf explants were infected with Agrobacterium
      rhizogenes, which induced hairy roots up to 21%. The transformed hairy root lines
      were confirmed by PCR using rolB and rolC gene-specific primers. Among various
      solid and liquid media, B5 liquid medium resulted maximum root biomass (36- fold
      higher) in 4-weeks. Quantitative analysis showed loganic acid was 6.6- fold
      higher in the presence of zeatin (1 mg/l) and gentiopicroside accumulation was
      1.8- fold higher in the presence of naphthaleneacetic acid (NAA, 1 mg/l), as
      compared to the roots of plants grown in greenhouse. On the other hand, 1.4- and
      2.5- fold higher gentiopicroside and swertiamarin were observed in the presence
      of 1.0 mg/l NAA as compared to commercial Gentiana herb No. 2. The result also
      showed iridoid and secoiridoid contents affected greatly by age, physiology and
      growing environment of the plant. CONCLUSIONS: The use of hairy root cultures is
      an excellent alternative to harvesting natural or in vitro grown plants to
      produce pharmaceutically important metabolites in less time with ensured quality.

PMID- 28510925
TI  - CsPI from the perianthless early-diverging Chloranthus spicatus show function on
      petal development in Arabidopsis thaliana.
AB  - BACKGROUND: In the floral ABC model, B-class genes comprised of DEFICIENS
      (DEF)/APETALA3 (AP3) and GLOBOSA (GLO)/PISTILLATA (PI) had been proposed to
      involve in second and third whorl floral organ development. However, less is
      known about the function of B-class genes from early-diverging angiosperms.
      Chloranthaceae is one of the early-diverging angiosperm families. In this study,
      we characterized the role of the PI-like gene CsPI cloned from Chloranthus
      spicatus which have the simplest perianthless bisexual flowers. RESULTS: The
      expression profile analysis reveals high levels of CsPI mRNA in stamens in
      Chloranthus spicatus, with weak distribution in leaves and other floral organs.
      Nevertheless, CsPI rescued both stamen and petal development in Arabidopsis
      thaliana pi-1 mutants and caused partially conversion of sepals into petaloid
      organs in wild-type Arabidopsis thaliana plants. Yeast two-hybrid analysis showed
      that CsPI can form not only homodimers but also heterodimers with proteins
      encoded by Arabidopsis thaliana and Chloranthus spicatus AP3-like genes.
      CONCLUSIONS: These results suggested that CsPI has an ancestral function on
      stamen development and that CsPI has capability to specify petal development in
      Arabidopsis thaliana. The finding indicates that the activity of the encoded PI
      like proteins is highly conserved between the early-diverging Chloranthus and
      Arabidopsis. Moreover, our results appear to suggest that B-function genes may
      not play a role in perianth development in Chloranthus spicatus.

PMID- 28510926
TI  - Sarocladium spinificis, a new endophytic species from the coastal grass Spinifex
      littoreus in Taiwan.
AB  - BACKGROUND: Sarocladium species are frequently associated with grasses as
      saprobes, parasites, and mutualistic endophytes. A species of Sarocladium
      (anamorphic Hypocreales) was isolated as endophytic fungus from the coastal grass
      Spinifex littoreus (Poaceae). RESULTS: According to characterization by LSU and
      ITS rDNA sequences and culture morphology and micromorphology, the species
      differed from the species hitherto described in Sarocladium. A key to the known
      species of Sarocladium is given. CONCLUSIONS: Sarocladium spinificis is proposed
      as a new species. LSU rDNA sequences and conidiophore branching and conidium size
      are useful characters for distinguishing between species of Sarocladium.

PMID- 28510928
TI  - Begonia wui-senioris (sect. Platycentrum, Begoniaceae), a new species from
      Myanmar.
AB  - BACKGROUND: The flora of Myanmar is under-collected compared with all other
      tropical Asian countries. An unknown Begonia was grown from seeds collected from
      a limestone hill in Central Myanmar, and compared with potentially allied
      species. RESULTS: The unknown Begonia is rhizomatous, has peltate leaves, 2
      locular ovaries, and is evergreen. It is clearly assignable to sect.
      Platycentrum. Only two other species of Begonia, B. josephii and B.
      subperfoliata, in Myanmar have peltate leaves, but they are deciduous tuberous
      plants with 3-locular ovaries and belong to sect. Diploclinium. CONCLUSIONS:
      Thorough studies of literature and herbarium materials support the recognition of
      a new species, Begonia wui-senioris, which is fully described and illustrated.
      Begonia wui-senioris has the lowest chromosome number (2n = 14) for the genus.

PMID- 28510927
TI  - Overproduction of valuable methoxylated flavones in induced tetraploid plants of
      Dracocephalum kotschyi Boiss.
AB  - BACKGROUND: Ploidy manipulation is considered an efficient method to increase
      production potential of medicinally important compounds. Dracocephalum kotschyi
      Boiss. is an endangered medicinal plant of Iran. Various concentrations of
      colchicine (0.05, 0.10, 0.20, and 0.50% w/v) were applied to shoot apical
      meristems of D. kotschyi seedlings in two and four-leaf stages to induce
      tetraploidy. RESULTS: According to the results, 0.5% (w/v) of colchicine can be
      effective for polyploidy induction in D. kotschyi. Putative tetraploids were
      selected by morphological and microscopic characteristics and their ploidy level
      was confirmed by flow cytometry analysis and chromosome counting. The chromosome
      number of original diploid plant was confirmed to be 2n = 2* = 20 whereas that of
      the tetraploid plant was 2n = 4* = 40. Tetraploid and mixoploid plants showed
      different morphological, physiological and microscopic characteristics from those
      of diploid counterparts. The total content of flavonoids was increased from
      1583.28 in diploids to 1890.07 (MUg/g DW) in stable tetraploids. CONCLUSION: High
      Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) confirmed
      over accumulation of methoxylated hydroxyflavones in solid tetraploid plants of
      D. kotschyi.

PMID- 28510929
TI  - Production and identification of haploid dwarf male sterile wheat plants induced
      by corn inducer.
AB  - BACKGROUND: Using the cross of wheat and maize is a very useful way to produce
      wheat haploid plants by chromosome elimination. Dwarf male sterile wheat (DMSW)
      and corn inducer are potential important germplasm for wheat breeding by
      recurrent selection and doubled haploid strategies. There is no report yet to
      achieve the haploid plants from DMSW induced by maize inbred line and especially
      the corn inducer. RESULTS: Haploid plants of DMSW were successfully obtained in
      this study induced by both maize pollens of inducer line and normal inbred line.
      The efficiencies for wheat embryos formation and plantlets production induced by
      the two corn lines had no significant difference. All the eleven haploid wheat
      plants derived from the male sterile material were identified by botanic
      appearance, cytology, cytogenetics, and molecular markers. They were all haploid
      based on their guard cell length of 42.78-42.90 MUm compared with the diploid
      control of 71.52 MUm, and their chromosome number of 21 compared with the diploid
      control of 42. In addition, according to anthers, plant height, and molecular
      markers, the haploid plants were divided into two types. Eight of them showed
      dwarf, having no anthers, and the special band of Rht10, and the other three
      plants displayed normal plant height, having anthers, and not containing the
      special band of Rht10, indicating that they were originated from the MS2/Rht10
      and ms2/rht10 female gametes, respectively. CONCLUSIONS: MS2/Rht10 haploid plants
      were successfully obtained in this study by using corn inducer and inbred line,
      and will be employed as candidate materials for the potential cloning of MS2
      dominant male gene.

PMID- 28510930
TI  - Functional characterization of the N-terminal and C-terminal domains of a sesame
      group II phytocystatin.
AB  - BACKGROUND: Phytocystatins are natural inhibitors of cysteine protease, and may
      regulate endo- or exo-genous proteolytic activities in plants. They are
      classified into Group I and II differing by the presence of C-terminal extension
      of Group II. A cDNA fragment encoding a Group II phytosystatin, SiCYS was
      previously obtained from sesame seeds. RESULTS: SiCYS as well as its two
      structural domains, N-terminal and C-terminal domains (SiCYS-N and SiCYS-C), was
      expressed in Escherichia coli. The recombinant SiCYS and SiCYS-N showed
      inhibitory activity against papain. The K i values of SiCYS and SiCYS-N were ~1.9
      *10-8 M and ~7.9 *10-8 M, respectively. All the three recombinants possessed
      comparable ability to inhibit spore germination of Trichoderma reesei,
      Aspergillus sydowii, and Helminthosporium sesamum. Similar protein profile
      including proteases in germinating seeds was found in proteins purified by the
      SiCYS, SiCYS-N or SiCYS-C coupling affinity column. CONCLUSION: SiCYS exhibited
      more effective papain-inhibitory activity than SiCYS-N; while SiCYS-C had almost
      no inhibitory activity. All displayed similar antifungal activities indicating
      that there is no correlation between antifungal and papain-inhibitory activities.
      Structural and sequence analyses suggest that the C-terminal domain of SiCYS may
      be originated from gene duplication to enhance its inhibitory activity.

PMID- 28510931
TI  - Application of an inducible transposon with anther culture in generation of di
      haploid homologous mutants.
AB  - BACKGROUND: Insertional mutagenesis represents one of the most effective ways to
      acquire information about a plant gene's function. However, it is hindered by the
      autosomal genome being diploid and therefore, most mutations being recessive. The
      problem is addressed by inducing the transposition during anther culture so that
      selected mutations can be transmitted and then regenerated to a homozygous state.
      RESULTS: To this end, we treated transgenic rice floral tissues containing the
      inducible transposon with an inducer, salicylic acid. Excision events were
      detected in regenerated calli and subsequent plantlets. DNA blot and PCR assay
      were used to determine the homogeneity of knockout mutants. About 5% of the
      mutants containing transposition events were homozygous. Furthermore, the
      inducible transposon was active during calli regeneration. CONCLUSIONS: This
      strategy could be applicable to improve transposition efficiency in microspore
      development stages to create stable di-haploid mutants in plants.

PMID- 28510932
TI  - Comparison of leaf anatomy and essential oils from Drimys brasiliensis Miers in a
      montane cloud forest in Itamonte, MG, Brazil.
AB  - BACKGROUND: Drimys brasiliensis Miers is native to Brazil, where it is mainly
      found in montane forests and flooded areas in the South and Southeast regions of
      the country. The objectives of the present study were to compare the leaf anatomy
      and the chemical constitution of the essential oils from D. brasiliensis present
      in two altitude levels (1900 and 2100 m), in a Montane Cloud Forest, in Itamonte,
      MG, Brazil. RESULTS: A higher number of sclereids was observed in the mesophyll
      of the leaves at 1900 m altitude. At 2100 m, the formation of papillae was
      observed on the abaxial surface of the leaves, as well as an increase in the
      stomatal density and index, a reduction in leaf tissue thickness, an increase in
      the abundance of intercellular spaces in the mesophyll and an increase in
      stomatal conductance and in carbon accumulation in the leaves. Fifty-nine
      constituents have been identified in the oils, with the predominance of
      sesquiterpenes. Two trends could be inferred for the species in relation to its
      secondary metabolism and the altitude. The biosyntheses of sesquiterpene alcohols
      at 1900 m, and phenylpropanoids and epi-cyclocolorenone at 2100 m, were favored.
      CONCLUSIONS: D. brasiliensis presented a high phenotypic plasticity at the
      altitude levels studied. In relation to its leaf anatomy, the species showed
      adaptive characteristics, which can maximize the absorption of CO2 at 2100 m
      altitude, where a reduction in the partial pressure of this atmospheric gas
      occurs. Its essential oils presented promising compounds for the future
      evaluation of biological potentialities.

PMID- 28510933
TI  - Histological characterization of the lateral root primordium development in rice.
AB  - BACKGROUND: Lateral root constitutes an important part of root system either in
      tap root plants or fibrous root plants. The development of lateral root
      primordium (LRP) in Arabidopsis, which has a tap root system with simple radial
      structure of primary root, has been well characterized. However, limited
      knowledge has been acquired on the plants with fibrous root system, such as rice.
      This is mainly due to their multiple cell layers coated on root, which disturb
      the observation of LRP. RESULTS: We used an easy and quick method to strip the
      epidermal and cortex tissues of primary root so that the LRP can be easily
      observed under microscope. In this way, we observed the developmental processes
      of LRP in rice. In addition, we described the expression dynamics of several root
      development related genes, especially OsPINs (PIN-FORWMED), during the process of
      LRP development. CONCLUSIONS: We reported an easy and quick method for LRP
      observation in rice and suggested a "fountain" model of auxin transport in LRP of
      rice, which is similar with that in Arabidopsis.

PMID- 28510934
TI  - The effects of the current and past meteorological elements influencing the
      current pollen concentrations for different taxa.
AB  - BACKGROUND: It is an important issue to separate the current and past components
      of the meteorological parameters influencing the current pollen concentration for
      different taxa. For this purpose a new statistical procedure, factor analysis
      with special transformation is introduced. The data set used covers an 11-year
      period (1997-2007) including daily pollen counts of 19 taxa and 4 climate
      variables (mean temperature, precipitation amount, global solar flux and relative
      humidity). RESULT: The taxa examined can be classified into three groups, namely
      arboreal deciduous (AD), arboreal evergreen (AE) and herbaceous (H) taxa. It was
      found that a better comparison can be established if the taxa are separated
      within each group according to the starting month of their pollen season. Within
      the group of AD taxa, Alnus, Populus and Ulmus are marked by a late summer -
      early autumn peak of the role of past meteorological elements exceeding the role
      of the current ones almost all over the pollen-free period. For Juglans, Morus,
      Platanus and Quercus, the major weights of the current meteorological elements in
      the spring and early summer show the most characteristic contribution to the
      pollen production. For AE taxa, the picture is no clear. For H taxa, the curves
      of Cannabis, Plantago, Rumex and Urtica indicate the most equalized course of
      weights. Ambrosia, Artemisia and Chenopodiaceae comprise the highest weights of
      the past weather conditions of all taxa until at least three months before the
      start of the pollination. Interactions between the phyto-physiological processes
      and the meteorological elements are evaluated. CONCLUSION: Separation of the
      weight of the current and past weather conditions for different taxa involves
      practical importance both for health care and agricultural production.

PMID- 28510935
TI  - Effect of short-term water deficit stress on antioxidative systems in cucumber
      seedling roots.
AB  - BACKGROUND: Cucumber is one of the most popular vegetables, and have little
      tolerance for water stress. The antioxidant defense system is one of major
      drought defense and adaptive mechanisms in plants, however, relatively few data
      are available regarding antioxidant systems in responses of cucumber to water
      deficit. The effect of short-term drought stress on the antioxidant system, lipid
      peroxidation and water content in cucumber seedlings roots was investigated.
      RESULTS: The results showed that polyethylene glycol (PEG) induced water stress
      markedly decreased water content of cucumber seedling roots after treatment of 36
      h, and caused excessive generation of reactive oxygen species (ROS) including
      superoxide (O2.-), hydrogen peroxide (H2O2). Meanwhile, malondialdehyde (MDA)
      content increased. Antioxidant enzymes including superoxide dismutases (SOD),
      peroxidases (POD), catalase (CAT) and ascorbate peroxidase (APX) activities
      increased in different time and different extent under water stress, while
      ascorbate (AsA) and glutathione (GSH) content, glutathione reductase (GR),
      dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR)
      activities all decreased when compared to control. CONCLUSIONS: Therefore, it can
      be concluded that water stress strongly disrupted the normal metabolism of roots
      and restrained water absorption, and seemingly enzymatic system played more
      important roles in protecting cucumber seedling roots against oxidative damage
      than non-enzymatic system in short-term water deficit stress.

PMID- 28510936
TI  - Effects of copper on leaf membrane structure and root activity of maize seedling.
AB  - BACKGROUND: Copper is an important heavy metal pollutant, with strong toxicity
      and great harm, which is easy to accumulate in the plant body and is difficult
      for degradation. This paper adopts medium culture method, taking "Zheng Dan 958"
      maize seedlings as sample materials. With different copper ion concentration
      gradients for the simulation of metal copper stress on maize seedlings, it
      explored the effects on the membrane structure (POD activity, MDA content,
      membrane permeability) and root activity. RESULTS: POD activity increases
      dramatically when the copper concentration is over 10 MUmol/L. MDA content
      increases sharply when the copper concentration is over 1000 MUmol/L, showing a
      rising trend. Membrane permeability increases greatly when the copper
      concentration is over 100 MUmol/L. Root activity decreases significantly when the
      copper concentration is 100 MUmol/L, showing a clear downward trend. CONCLUSIONS:
      The copper concentration of 1000 MUmol/L has exceeded the maize seedling
      tolerance to copper, and the activities of protective enzymes of maize seedlings
      are inhibited. Cell membrane lipid peroxidation has caused serious damage on the
      structure and function of membrane. Structure of root cells of maize seedling is
      also damaged, reducing the root activity, so the maize is irreversible hurt.

PMID- 28510937
TI  - The seed development of a mycoheterotrophic orchid, Cyrtosia javanica Blume.
AB  - BACKGROUND: Cyrtosia javanica is a rare, mycoheterotrophic vanilloid orchid
      native to the bamboo forest in central Taiwan. Like some vanilloid orchids, the
      seeds of C. javanica are hard and difficult to germinate in vitro. A better
      understanding of the embryology would provide insights in the propagation and
      conservation of this rare species. RESULTS: Based on the histological and
      histochemical studies, we observed some remarkable features in developing seeds
      of C. javanica. First, the developing embryos without a structurally defined
      suspensor; Second, the chalazal accessory cells have densely stained cytoplasms
      that are different from the adjacent cells of seed coat; Third, the multiple
      layers of seed coat with the lignified in the outermost cell layer of the outer
      seed coat. CONCLUSIONS: In C. javanica, the large and heavy seeds embedded in
      fresh fruits may adapt to the dispersal strategy. The hard seeds with lignified
      outer seed coat could provide a rigid protection during seed dispersal but also
      cause coat-imposed dormancy. This study provides insights in the seed coat
      structure and the hints of seed treatment methods.

PMID- 28510938
TI  - Fatty acid, tocopherol and squalene contents of Rosaceae seed oils.
AB  - BACKGROUND: The aim of current study is to establish the composition of these
      seeds belong to Rosaceae family with respect to fatty acid, tocopherol and
      squalene content. RESULTS: The oil contents of seeds varied between 3.49
      (Cotoneaster bullatus) to 46.15 g/100 g (Prunus tenella). The main fatty acids of
      seed oils were oleic (6.50 - 67.11 %), linoleic (22.08 - 68.62 %) and 20:1n-7
      (0.10 - 61.59 %). As observed, the oils of seed were rich in linoleic and oleic
      acids. Total tocopherol contents ranged between 7.06 mg/100 g (Prunus tenella) to
      165.74 mg/100 g (Potentilla glandulosa ssp. pseudorupestris). The major
      tocopherols were gamma-tocopherol, ranging from 2.08 mg/100 g to 106.01 mg/100 g;
      alpha-tocopherol ranging from 2.86 mg100 g to 74.26 mg/100 g and delta-tocopherol
      ranging used in this experiment were found between 0.02 mg/100 g (Alchemilla
      caucasica) to o.29 mg/100 g (Cotoneaster simonsii). CONCLUSIONS: These results
      show that Rosaceae seed oils can be a potential saurce of valuable oil which
      might be useful for the evaluation of dietary information in important food crops
      and other industrial applications.

PMID- 28510939
TI  - A new Haniffia species (Zingiberaceae) and a new generic record from Sarawak,
      Malaysian Borneo.
AB  - BACKGROUND: Haniffia Holttum is a genus of three described species of terrestrial
      gingers hitherto restricted to Peninsular Thailand and various localities in
      Peninsular Malaysia. RESULTS: With generic placement confirmed using nrITS, trn K
      and mat K plastid sequence data, Haniffia santubongensis S.Y. Wong & P.C. Boyce
      is described as a taxonomically novel species representing a new generic record
      for Borneo, to where it is endemic to Mount Santubong, Kuching Division, NW
      Sarawak, Malaysian Borneo. An identification key to all species is given and H.
      santubongensis is illustrated from living plants. CONCLUSION: Haniffia
      santubongensis is the fourth species of Haniffia so far described, and the first
      occurring on sandstone.

PMID- 28510940
TI  - Comparison of soil bacterial communities in a natural hardwood forest and
      coniferous plantations in perhumid subtropical low mountains.
AB  - BACKGROUND: The bacterial community of forest soils is influenced by
      environmental disturbance and/or meteorological temperature and precipitation. In
      this study, we investigated three bacterial communities in soils of a natural
      hardwood forest and two plantations of conifer, Calocedrus formosana and
      Cryptomeria japonica, in a perhumid, low mountain area. By comparison with our
      previous studies with similar temperature and/or precipitation, we aimed to
      elucidate how disturbance influences the bacterial community in forest soils and
      whether bacterial communities in similar forest types differ under different
      climate conditions. RESULTS: Analysis of 16S ribosomal RNA gene clone libraries
      revealed that Acidobacteria and Proteobacteria were the most abundant phyla in
      the three forest soil communities, with similar relative abundance of various
      bacterial groups. However, UniFrac analysis based on phylogenetic information
      revealed differences of bacterial communities between natural hardwood forest and
      coniferous plantation soils. The diversities of bacterial communities of the
      replanted Calocedrus and Cryptomeria forests were higher than that in natural
      hardwood forest. The bacterial diversity of these three forest soil were all
      higher than those in the same forest types at other locations with less
      precipitation or with lower temperature. In addition, the distribution of some of
      the most abundant operational taxonomic units in the three communities differed
      from other forest soils, including those related to Acidobacteria, alpha-, beta-
      and gamma-Proteobacteria. CONCLUSIONS: Reforestation could increase the bacterial
      diversity. Therefore, soil bacterial communities could be shaped by the forestry
      management practices and climate differences in warm and humid conditions.

PMID- 28510941
TI  - Vasorelaxing and antihypertensive activities of synthesized peptides derived from
      computer-aided simulation of pepsin hydrolysis of yam dioscorin.
AB  - BACKGROUND: We reported that yam dioscorin and its peptic hydrolysates exhibited
      ACE inhibition and antihypertensive effects on SHRs, however, the active peptides
      are not really isolated until now. Using ACE inhibitory screenings, two penta
      peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments.
      RESULTS: KTCGY, KRIHF, and captopril were shown to have similar vasodilating
      effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent
      thoracic aortic rings, however, KTCGYKTCGY (two-repeated KTCGY) and TCGYTCGY (two
      repeated TCGY) were showed endothelium-independent vasodilating effects against
      PE-induced tensions. KTCGY, KRIHF (10 or 20 mg/kg), and captopril (10 mg/kg) were
      used to evaluate antihypertensive activity during 24-h after a single oral
      administration to spontaneously hypertensive rats (SHRs). The KTCGY and KRIHF
      showed significantly different and reduced the systolic blood pressure of SHRs
      compared to the blank. CONCLUSIONS: These results suggest that KTCGY and KRIHF
      may contribute important roles in yam dioscorin for regulating blood pressure in
      vivo.

PMID- 28510942
TI  - In vitro propagation and analysis of secondary metabolites in Glossogyne
      tenuifolia (Hsiang-Ju) - a medicinal plant native to Taiwan.
AB  - BACKGROUND: Glossogyne tenuifolia Cassini (Hsiang-Ju in Chinese) is a perennial
      herb native to Penghu Islands, Taiwan. The herb is a traditional anti-pyretic and
      hepatoprotective used in Chinese medicine. Several studies on G. tenuifolia have
      demonstrated its pharmacological values of antioxidation, anti-inflammation,
      immunomodulation, and cytotoxicity on several human cancer cell lines. Active
      compounds, oleanolic acid and luteolin in G. tenuifolia are affected by several
      factors, including climatic change, pathogens and agricultural practices. Plant
      population of G. tenuifolia has been severely affected and reduced considerably
      in natural habitat due to the use of herbicides by farmers. Also, collection of
      plant material from the natural habitat is restricted to a few months in a year.
      Therefore, the objective of the present study was to develop an efficient
      micropropagation protocol for G. tenuifolia. The study also aimed to investigate
      the influence of in vitro growth environment on the active compounds in in vitro
      shoots, tissue culture raised greenhouse plants; compare the values with wild
      plants and commercially available crude drug. RESULTS: Half-strength MS
      (Murashige and Skoog) basal medium supplemented with 0.1 mg/L 6-benzyladenine
      (BA) and 0.1 mg/L alpha-naphthaleneacetic acid (NAA) induced the maximum average
      number of shoots (7.3) per shoot tip explant excised from in vitro grown
      seedlings. Induction of rooting in cent percent in vitro shoots with an average
      number of 6.6 roots/shoot was achieved on 1/2 strength MS medium supplemented
      with 3.0 mg/L indole-3-acetic acid (IAA). The rooted plantlets acclimatized
      successfully in the greenhouse with a 100% survival rate. HPLC analysis revealed
      that the quantity of oleanolic acid and luteolin in in vitro shoots, tissue
      culture plants in the greenhouse, wild type plants and commercial crude drug
      varied depending upon the source. The oleanolic acid and luteolin contents were
      found to be significantly higher (16.89 mg/g and 0.84 mg/g, respectively) in 3
      month old tissue culture raised plants in greenhouse compared to commercially
      available crude drug (6.51 mg/g, 0.13 mg/g, respectively). CONCLUSIONS: We have
      successfully developed an in vitro propagation protocol for G. tenuifolia which
      can expedite its plant production throughout the year. The contents of oleanolic
      acid and luteolin in the tissue culture raised plants in the greenhouse were
      significantly higher than the marketed crude drug demonstrating the practical
      application of the tissue culture technology. These findings may be very useful
      in micropropagation, germplasm conservation and commercial cultivation of G.
      tenuifolia. So far, there is no published report on tissue culture propagation of
      this important medicinal plant species.

PMID- 28510943
TI  - Two new species of Begonia sect. Coelocentrum, B. guixiensis and B. longa, from
      Sino-Vietnamese limestone karsts.
AB  - BACKGROUND: In our recent molecular phylogenetic study of Asian Begonia, two
      undescribed species, B. guixiensis sp. ined. (S. Guangxi, China) and B. longa sp.
      ined. (Vietnam), were sampled and placed within the strongly supported clade
      composed of Begonia sect. Coelocentrum and other co-distributed rhizomatous
      species in the Sino-Vietnamese limestone karsts. While Begonia sect. Coelocentrum
      has been recircumscribed based on the phylogenetic relationships, B. guixiensis
      sp. ined. and B. longa sp. ined. remain illegitimate names. In continuation of
      our studies in Asian Begonia, these two new species are described and
      illustrated. RESULTS: Begonia guixiensis resembles B. cylindrica in the peltate,
      subcoriaceous leaves, differing by the shape of ovary/fruit and the type of
      placentation. In aspect, B. longa bears a superficial resemblance to B.
      brevipedunculata in leaf shape in particular, differing by many other features
      such as the long internodes, shorter petioles and smaller leaves, longer
      peduncles and 3-locular ovary. The chromosome number of both new species is
      determined as 2n = 30. CONCLUSION: A careful study of the literature, herbarium
      specimens and living plants, both in the wild and in cultivation in the
      experimental greenhouse, support the recognition of the two new species, which
      are described and illustrated herein.

PMID- 28510944
TI  - Antioxidant activities of two metallothionein-like proteins from sweet potato
      (Ipomoea batatas [L.] Lam. 'Tainong 57') storage roots and their synthesized
      peptides.
AB  - BACKGROUND: Metallothionein (MT) characterized by their low molecular weight and
      high cysteine content. RESULTS: Two recombinant proteins of MT-I and MT-II
      overproduced in E. coli (M15) was purified by Ni2+-chelated affinity
      chromatography. The molecular mass of MT-I and MT-II are ca. 6,600 and 8,000 Da
      as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). Total antioxidant status, DPPH radical scavenging activity, reducing power
      method, Fe2+-chelating ability, ferric thiocyanate (FTC) method, and protecting
      calf thymus DNA against hydroxyl radical-induced damage were studied. The MT-I
      and MT-II proteins with a concentration of 100 MUg/mL exhibited the highest
      activity (expressed respectively as 61.72 +/- 0.13 and 74.28 +/- 1.15 MUM Trolox
      equivalent antioxidative capacity, TEAC) in total antioxidant status test. Like
      total antioxidant status, DPPH radical scavenging activity, reducing power, Fe2+
      chelating ability, FTC activity, and protecting calf thymus DNA against hydroxyl
      radical-induced damage all showed that MT-1 and MT-II proteins have antioxidant
      activities. In this study, we also found that antioxidant activities of MT-I and
      MT-II increased from 17% and 16% (0 h) to about 26% and 28% (24 h) after 24 h
      hydrolysis by trypsin. Smaller peptides increased the antioxidant activities.
      Four and three peptides, respectively, from MT-I and MT-II protein sequences for
      testing antioxidative activity were synthesized according to tryptic hydrolysis
      simulation. The obtained MSSGCK, CGSDCK, LTLEGSSEK, ATEGGHACK, CGNGCGGCK, and
      CDPCNCK showed IC50 values of 309.87, 1423.37, 3925.54, 561.32, 300.76, and
      610.12 MUM, respectively, when scavenging activity of DPPH radicals (%) was
      measured. CONCLUSIONS: These findings mean that a cysteine residue is most
      important in antiradical activities. It was suggested that MT-I and MT-II might
      contribute their antioxidant activities against hydroxyl and peroxyl radicals.

PMID- 28510945
TI  - Fusaric acid induced cell death and changes in oxidative metabolism of Solanum
      lycopersicum L.
AB  - BACKGROUND: Fusaric acid (FA) has been shown to stimulate the rapid development
      of disease symptoms, such as necrosis and foliar desiccation. In this study, we
      have evaluated the phytotoxicity of FA on tomato plants (Solanum lycopersicum
      L.). FA induced necrotic lesions in detached leaves, which are reminiscent of
      hypersensitive response (HR) lesions induced by plant-pathogen interactions and
      other abiotic stress factors. RESULTS: FA-treated tomato leaves exhibited visible
      necrotic lesion as a result of cell death which was evident by Evans blue
      staining, enhanced reactive oxygen species (ROS) levels and DNA degradation.
      Changes in the generation of O2.- and H2O2 as well as the activities of
      superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) were
      examined in FA-treated tomato leaves. It was observed that FA exposure stimulated
      oxidative burst in the leaves, resulting in a lasting activation of O2.- and H2O2
      production. After first day of FA application, the H2O2 scavenging enzymes CAT
      and APX showed a strong activity decrease followed by gradual recovery to the
      control level after 2 and 3 days. CONCLUSION: A concomitant increase in ROS
      production, the down regulation of antioxidative enzymes activities and
      upregulation of lipid peroxidation were crucial for the onset of cell death.
      These results suggested that FA-induced damage might result from ROS pathways.
      Thus, our experiments provide a useful model plant system for research on FA
      induced plant cell death.

PMID- 28510946
TI  - Aluminum induces rapidly mitochondria-dependent programmed cell death in Al
      sensitive peanut root tips.
AB  - BACKGROUND: Although many studies suggested that aluminum (Al) induced programmed
      cell death (PCD) in plants, the mechanism of Al-induced PCD and its effects in Al
      tolerance is limited. This study was to investigate the mechanism and type of Al
      induced PCD and the relationship between PCD and Al tolerance. RESULTS: In this
      study, two genotypes of peanut 99-1507 (Al tolerant) and ZH2 (Al sensitive) were
      used to investigate Al-induced PCD. Peanut root growth inhibition induced by
      AlCl3 was concentration and time-dependent in two peanut varieties. AlCl3 at 100
      MUM could induce rapidly peanut root tip PCD involved in DNA cleavage, typical
      apoptotic chromatin condensation staining with DAPI, apoptosis related gene
      Hrs203j expression and cytochrome C (Cyt c) release from mitochondria to cytosol.
      Caspase3-like protease was activated by Al; it was higher in ZH2 than in 99-1507.
      Al increased the opening of mitochondrial permeability transition pore (MPTP),
      decreased inner membrane potential (DeltaPsim) of mitochondria. Compared with the
      control, Al stress increased O2*- and H2O2 production in mitochondria. Reactive
      oxygen species (ROS) burst was produced at Al treatment for 4 h. CONCLUSIONS: Al
      induced PCD is earlier and faster in Al-sensitive peanut cultivar than in Al
      tolerant cultivar. There is a negative relationship between PCD and Al
      resistance. Mitochondria- dependence PCD was induced by Al and ROS was involved
      in this process. The mechanism can be explained by the model of acceleration of
      senescence under Al stress.

PMID- 28510947
TI  - Generic affiliations of Canthium species placed under Pyrostria group B sensu
      Bridson (Vanguerieae, Rubiaceae) inferred from morphology and molecular data.
AB  - BACKGROUND: Pyrostria sensu lato (s.l.) is regarded as one of the polyphyletic
      group within Vanguerieae formerly comprising of Pyrostria sensu stricto (s.s.),
      Pyrostria group A and Pyrostria group B delineated by the number of locules and
      geographical occurrence. Recent molecular phylogenetic studies within the genus
      have narrowed its circumscription that resulted in the merging of Pyrostria group
      A and Pyrostria s.s. Although some species of Pyrostria group B were already
      transferred to Pyrostria s.s. and Psydrax based on morphology, other
      representatives of the group remain unsettled. RESULTS: Bayesian and parsimony
      analysis of the combined ITS (nrDNA) and trnL-F (cpDNA) datasets showed a well
      supported clade of the whole Vanguerieae containing four Philippine endemic
      representatives of Pyrostria group B. The placement of Canthium oligophlebium,
      Canthium obovatifolium and Canthium ramosii within Pyrostria s.s. (PP = 0.99; BS
      = 85%) is robustly supported likewise the affiliation of C. gynochthodes with
      Psydrax (PP = 0.94; BS = 85%). Morphological features shared by our species with
      Pyrostria s.s. and Psydrax further supports our molecular data. CONCLUSION: Our
      study supports the earlier hypothesis that Canthium oligophlebium, C.
      obovatifolium and C. ramosii should be placed under Pyrostria s.s. except for C.
      gynochthodes that grouped with Psydrax. Four new combinations are proposed in
      this study. The generic affiliations of other species of Pyrostria group B should
      be reinvestigated towards a more natural classfication in Vanguerieae.

PMID- 28510948
TI  - A new variant produced by Rhizoctonia solani AG1-IC isolate CH-1 with a new type
      of nuclei.
AB  - BACKGROUND: Isolate CH-1 of Rhizoctonia solani Kuhn was commonly used in our
      studies of the pathogenicity and genetics of this pathogen. During the
      preparation of homokaryons through protoplast regeneration and tuft formation, a
      defective homokaryon was detected and a new variant was obtained. RESULTS: When
      tuft formation was used to identify the karyotic nature of single protoplast
      regenerants (SPRs) of Rhizoctonia solani AG1-IC isolate CH-1, one homokaryon type
      designated as A type and the parental heterokaryon designated as AB type were
      obtained. The homokaryon B type was not found. Various approaches were used to
      obtain SPRs, including from fast or slow growing protoplast regenerants, and from
      regenerants of protoplasts released from mycelia grown in different nutrient
      broths or at different temperatures. Without exception, all these SPRs were
      either homokaryon A or heterokaryon AB. Moreover, the SPRs obtained from
      different generations of SPRs, and from different generations of SPRs treated
      with lytic enzymes 3 to 4 times also were invariably either homokaryon A or
      heterokaryon AB. When single hyphal isolates were obtained from the tuft
      resulting from the pairing between homokaryon A and heterokaryon AB, only the
      heterokaryon and a variant were obtained. The variant did not form tuft when
      paired with parental heterokaryon AB or homokaryon A. Its protoplast regenerants
      gave rise to heterokaryon AB, homokaryon A and the variant, indicating that it is
      a new kind of heterokaryon. CONCLUSION: Inability to obtain homokaryon B despite
      numerous attempts suggests that the B type nuclei are probably defective and are
      dependent on A type nuclei for their multiplication. This is the first report of
      a heterokaryotic R. solani strain carrying a defective type of nuclei. A new
      variant which is a new kind of heterokaryon was obtained from the tuft resulting
      from the paring between the homokaryon A and the parental heterokaryon AB.

PMID- 28510949
TI  - Thermoregulation in the appendix of the Sauromatum guttatum (Schott)
      inflorescence.
AB  - BACKGROUND: Three phenolic compounds are capable of activating the process that
      simultaneously leads to temperature rise and odor-production in the Sauromatum
      appendix. These compounds are salicylic acid, aspirin, and 2,6 dihydroxybenzoic
      acid. The objectives of the present study were to examine the effect of various
      concentrations of the these inducers on the temperature rise and to study the
      effect of mitochondrial inhibitors (KCN and SHAM) and an uncoupler (DNP) on the
      temperature rise. RESULTS: In sections of the Sauromatum appendix two successive
      temperature rate maxima were detected in the presence of the three inducers. Two
      temperature maxima were also detected in appendices of intact inflorescences. The
      temperature profiles demonstrated a considerable variability within sections of
      one appendix in both magnitude and time of reaching a peak. When the Sauromatum
      temperature decreased it returned either to the same temperature baseline or to a
      slightly different baseline. The temperature rise was blocked by KCN (20 mM) and
      SHAM (40 mM) alone or when added together. DNP, an uncoupler, at 2.5 mM also
      blocked the rise in temperature. The thermogenic inducers also triggered a
      temperature rise in Arum appendix. CONCLUSIONS: The presence of two rate maxima
      may indicate different heat-generating sources. The blockage of the temperature
      rise in the presence of KCN or SHAM implies that the activity of the cyanide
      resistant and -sensitive pathways is required for generating heat. The
      variability in temperature profiles maybe related to changes in cellular control
      factors. This study provides the basis for investigating thermoregulation in
      plants.

PMID- 28510950
TI  - Arbuscular mycorrhizal fungi increase salt tolerance of apple seedlings.
AB  - BACKGROUND: Apple trees are often subject to severe salt stress in China as well
      as in the world that results in significant loss of apple production. Therefore
      this study was carried out to evaluate the response of apple seedlings inoculated
      with abuscular mycorrhizal fungi under 0, 20/00, 40/00 and 60/00 salinity stress
      levels and further to conclude the upper threshold of mycorrhizal salinity
      tolerance. RESULTS: The results shows that abuscular mycorrhizal fungi
      significantly increased the root length colonization of mycorrhizal apple plants
      with exposure time period to 0, 20/00 and 40/00 salinity levels as compared to
      non-mycorrhizal plants, however, percent root colonization reduced as saline
      stress increased. Salinity levels were found to negatively correlate with leaf
      relative turgidity, osmotic potential irrespective of non-mycorrhizal and
      mycorrhizal apple plants, but the decreased mycorrhizal leaf turgidity maintained
      relative normal values at 20/00 and 40/00 salt concentrations. Under salt stress
      condition, Cl- and Na+ concentrations clearly increased and K+ contents obviously
      decreased in non-mycorrhizal roots in comparison to mycorrhizal plants, this
      caused mycorrhizal plants had a relatively higher K+/Na+ ratio in root. In
      contrast to zero salinity level, although ascorbate peroxidase and catalase
      activities in non-inoculated and inoculated leaf improved under all saline
      levels, the extent of which these enzymes increased was greater in mycorrhizal
      than in non-mycorrhizal plants. The numbers of survived tree with non
      mycorrhization were 40, 20 and 0 (i.e., 66.7%, 33.3% and 0) on the days of 30, 60
      and 90 under 40/00 salinity, similarly in mycorrhization under 60/00 salinity 40,
      30 and 0 (i.e., 66.7%, 50% and 0) respectively. CONCLUSION: These results suggest
      that 20/00 and 40/00 salt concentrations may be the upper thresholds of salinity
      tolerance in non-mycorrhizal and mycorrhizal apple plants, respectively.

PMID- 28510951
TI  - Hyphoderma pinicola sp. nov. of H. setigerum complex (Basidiomycota) from Yunnan,
      China.
AB  - BACKGROUD: Hyphoderma setigerum (Fr.) Donk is a white-rot wood-decaying corticoid
      fungal species. It occurs worldwide from tropical to temperate regions. However,
      taxonomic studies in recent decades showed that H. setigerum is a species complex
      with four separate species, before this study. RESULTS: Hyphoderma pinicola sp.
      nov. was collected on dead wood of Pinus yunnanensis Franch. in the temperate
      montane belt at 2200-2400 m altitudes, in Yunnan Province of China. Within the H.
      setigerum complex this new taxon is distinguished by having 2-sterigmate basidia,
      long basidiospores, and nearly naked septocystidia. A description and
      illustrations of this new species are provided, along with a key to five species
      of the H. setigerum complex. Phylogenetic reconstruction based on 5.8S-ITS2
      sequences indicated that H. pinicola belongs to the H. setigerum complex and has
      a separate position within the clade including H. subsetigerum and H. setigerum
      s.s. Bayesian inference of phylogeny based on two datasets, ITS and 28S nuclear
      ribosomal DNA sequences, confirmed the independent status of H. pinicola.
      CONCLUSION: Morphological and phylogenetic studies showed that H. pinicola
      represents a fifth species of H. setigerum complex.

PMID- 28510952
TI  - Analysis of microsatellites in the vulnerable orchid Gastrodia flavilabella: the
      development of microsatellite markers, and cross-species amplification in
      Gastrodia.
AB  - BACKGROUND: Gastrodia flabilabella is a mycoheterotrophic orchid that obtains
      carbohydrates and nutrients from its symbiotic mycorrhizal fungi. The species is
      an endemic and vulnerable species enlisted in the "A Preliminary Red List of
      Taiwanese Vascular Plants" according to the IUCN Red List Categories and Criteria
      Version 3.1. G. flabilabella dwells the underground of broadleaf and coniferous
      forest with richness litter. Based on herbarium records, this species is
      distributed in central Taiwan. Twenty eight microsatellite loci were developed in
      G. flabilabella and were tested for cross-species amplification in additional
      taxa of G. confusoides, G. elata, and G. javanica. We estimated the genetic
      variation that is valuable for conservation management and the development of the
      molecular identification system for G. elata, a traditional Chinese medicine
      herb. RESULTS: Microsatellite primer sets were developed from G. flabilabella
      using the modified AFLP and magnetic bead enrichment method. In total, 257
      microsatellite loci were obtained from a magnetic bead enrichment SSR library. Of
      the 28 microsatellite loci, 16 were polymorphic, in which the number of alleles
      ranged from 2 to 15, with the observed heterozygosity ranging from 0.02 to 1.00.
      In total, 15, 13, and 7 of the loci were found to be interspecifically
      amplifiable to G. confusoides, G. elata, and G. javanica, respectively.
      CONCLUSIONS: Amplifiable and transferable microsatellite loci are potentially
      useful for future studies in investigating intraspecific genetic variation,
      reconstructing phylogeographic patterns among closely related species, and
      establishing the standard operating system of molecular identification in
      Gastrodia.

PMID- 28510954
TI  - Hydraulic conductivity and contribution of aquaporins to water uptake in roots of
      four sunflower genotypes.
AB  - BACKGROUND: This article evaluates the potential of intraspecific variation for
      whole-root hydraulic properties in sunflower. We investigated genotypic
      differences related to root water transport in four genotypes selected because of
      their differing water use efficiency (JAC doi: 10.1111/jac.12079. 2014). We used
      a pressure-flux approach to characterize hydraulic conductance (L 0 ) which
      reflects the overall water uptake capacity of the roots and hydraulic
      conductivity (Lp r ) which represents the root intrinsic water permeability on an
      area basis. The contribution of aquaporins (AQPs) to water uptake was explored
      using mercuric chloride (HgCl2), a general AQP blocker. RESULTS: There were
      considerable variations in root morphology between genotypes. Mean values of L 0
      and Lp r showed significant variation (above 60% in both cases) between
      recombinant inbred lines in control plants. Pressure-induced sap flow was
      strongly inhibited by HgCl2 treatment in all genotypes (more than 50%) and
      contribution of AQPs to hydraulic conductivity varied between genotypes. Treated
      root systems displayed markedly different L 0 values between genotypes whereas Lp
      r values were similar. CONCLUSIONS: Our analysis points to marked differences
      between genotypes in the intrinsic aquaporin-dependent path (Lp r in control
      plants) but not in the intrinsic AQP-independent paths (Lp r in HgCl2 treated
      plants). Overall, root anatomy was a major determinant of water transport
      properties of the whole organ and can compensate for a low AQP contribution.
      Hydraulic properties of root tissues and organs might have to be taken into
      account for plant breeding since they appear to play a key role in sunflower
      water balance and water use efficiency.

PMID- 28510955
TI  - Molecular cloning and characterization of a thioredoxin from Taiwanofungus
      camphorata.
AB  - BACKGROUND: Thioredoxin (Trx) is reduced by thioredoxin reductase. Trx is used in
      ribonucleoide reduction, assimilatory sulfate reduction, in modulation of protein
      sulfhydryl groups, and refolding proteins. RESULTS: A TcTrx (Tc: Taiwanofungus
      camphorata) cDNA (640 bp, GenBank AY838902.1) encoding a putative thioredoxin
      (Trx) of 135 amino acid residues with calculated molecular mass of 16.17 kDa was
      cloned from Taiwanofungus c amphorata. The deduced amino acid sequence containing
      a motif (Cys-Gly-Pro-Cys) that is highly conserved among the reported Trxs. A
      three dimensional structural model of the TcTrx has been created based on the
      known structure of Malassezia sympodialis Trx (MsTrx, PDB ID: 2j23). To
      characterize the TcTrx, the codon optimized coding region was subcloned into an
      expression vector and transformed into Saccharomyces cerevisiae. The recombinant
      His8-tagged TcTrx was expressed and purified by Ni affinity chromatography. The
      purified enzyme showed a band of approximately 32 kDa (expected dimeric form) on
      a 12% SDS-PAGE. The molecular mass determined by MALDI-TOF is 33.16 kDa which
      suggests that the purified enzyme is a dimeric enzyme. Furthermore, the enzyme
      exhibited TcTrx activity via insulin assay. The Michaelis constant (K M ) value
      for insulin was 3.78 * 10-2 mM. The enzyme's half-life of deactivation was 13 min
      at 45 degrees C. The enzyme was most active at pH 7. CONCLUSIONS: A three
      dimensional structural model of T. camphorata Trx based on its TcTrx cDNA
      sequence. The active form of the TcTrx has been successfully expressed in yeast.
      The enzyme possesses Trx activity and is capable of reduction of disulfide bonds
      during the formation of newly synthesized proteins.

PMID- 28510953
TI  - Microsatellite resources of Eucalyptus: current status and future perspectives.
AB  - Eucalyptus is the premier paper pulp, short rotation plantation species grown all
      over the world. Genetic improvement programs integrating molecular marker tools
      are in progress in many parts of the globe to increase the productivity. Whole
      genome sequence and expressed sequence tags (ESTs) of the eucalypts paved way for
      introduction of molecular genetics and breeding in this genus. Different
      molecular characterization approaches have been used simultaneously in eucalypts,
      however, microsatellites or simple sequence repeats (SSRs) with their prolific
      characteristics could occupy a special niche in Eucalyptus genetic improvement.
      Further, highly informative SSRs were used for the clonal identity, genetic
      fidelity and in certification of breeder's rights. Eucalyptus genetic linkage
      maps generated with microsatellite loci were used successfully to identify
      quantitative trait loci (QTLs) for various economically important traits.
      Progressively more numbers of microsatellites are being linked to genes
      associated with adaptive and functional variations, therefore making their
      utility broader in genetic applications. Availability of common SSR markers
      across the species provides an opportunity to validate the expression of QTLs
      across variable genetic backgrounds and accurately compare the position of QTLs
      in other species. Recent evidences suggest that the presence of SSRs in micro
      RNAs of plant species play a role in the quantitative trait expression. Similar
      studies in eucalypts may provide new insights into the genetic architecture of
      transcript-level variations and post transcriptional gene regulation. This review
      on eucalypts microsatellites, highlights the availability and characteristics of
      genomic and eSSRs and their potential in genetic analysis of natural and breeding
      populations and also discusses the future prospects in population genetics and
      marker assisted selection.

PMID- 28510956
TI  - Essential oil variation in wild populations of Artemisia saharae (Asteraceae)
      from Tunisia: chemical composition, antibacterial and antioxidant properties.
AB  - BACKGROUND: Artemisia saharae Pomel is a new taxon of Artemisia herba-alba Asso
      (Asteraceae) which is endemic to Tunisia and Algeria. This shrub, commonly known
      as white wormwood or desert wormwood, is largely used in folk medicine and as a
      culinary herb. The bulks aromatic plants come from wild populations whose
      essential oils compositions as well as their biological properties are severely
      affected by several factors such as geographic conditions. Therefore, the aim of
      the present work is to provide more information about the influence of altitude
      variation on the essential oil composition, antimicrobial and antioxidant
      properties of Artemisia saharae growing wild in the same geographical area.
      RESULTS: Essential oils were extracted by hydrodistillation of leaves and flowers
      of the plant collected from seven different altitudes of the Baten Zamour region
      (southwest of Tunisia). The highest essential oil yields (2.70-2.80%) were
      obtained for populations of high altitudes. Seventy-five compounds, representing
      92.78 to 96.95% of the total essential oils, were separated and identified.
      Essential oils were characterized by very high percentage of oxygenated
      monoterpenes (52.1-72.6%) which constituted the predominant class. From the
      analyzed populations, the major compounds (>7%) were alpha-thujone, beta-thujone,
      chrysanthenone, camphor, chrysanthenyl acetate, and sabinyl acetate. Sabinyl
      acetate which was detected in some populations at relatively high percentages
      (7.7-10.8%) seems to be characteristic to Southern Tunisian A. saharae. The
      studied essential oil showed a chemical diversity depending on the population
      altitude as revealed by linear discriminant and cluster analyses. CONCLUSIONS:
      Three population groups associated with altitudinal levels were distinguished. It
      is worthy to note that the most discriminating compounds of chemical groups were
      the minor ones. Despite the high variation of essential oil compositions, the
      high altitude population did not affect severely the antibacterial activity
      against the most tested strains. Altitude seems to be an important factor
      influencing the yield and the chemical profile of Artemisia saharae essential
      oils. Knowledge of the chemical composition of essential oils in relation to
      environmental factors is a very important quality criterion for their marketing
      and contributes to their valorization as functional ingredient in food
      technology.

PMID- 28510957
TI  - Antioxidant, cell-protective, and anti-melanogenic activities of leaf extracts
      from wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.)
      cultivars.
AB  - BACKGROUND: Several wild bitter melon (WBM; Momordica charantia Linn. var.
      abbreviata Ser.) cultivars were developed in Taiwan. However, little information
      is available regarding biological function of WBM leaf. Therefore, the objectives
      of this study were to investigate the nutrient content, antioxidant, cell
      protection and anti-melanogenic properties of wild bitter melon leaf. RESULTS:
      Methanolic leaf extracts were prepared from a variety and two cultivars of WBM.
      All extracts exerted potent nitric oxide and hydroxyl radical scavenging
      capacities. Furthermore, all extracts effectively reduce the production of
      reactive oxygen species and prevent cell death in UVB-irradiated HaCaT
      keratinocytes. The cell protective effect of leaf extract was also investigated
      by the prevention of HaCaT cells from sodium nitroprusside or menadione-induced
      toxicity, and significant cyto-protective activities were observed for all of
      them. Additionally, all extracts significantly suppressed tyrosinase activity and
      melanin levels in B16-F10 melanocytes. CONCLUSIONS: WBM leaf extract showed
      significant antioxidant, cyto-protective and anti-melanogenic activities. These
      findings suggested that WBM leaves may be beneficial for preventing the photo
      oxidative damage and melanogenesis of skin.

PMID- 28510959
TI  - Fire induced reproductive mechanisms of a Symphoricarpos (Caprifoliaceae) shrub
      after dormant season burning.
AB  - BACKGROUND: Symphoricarpos, a genus of the Caprifoliaceae family, consists of
      about 15 species of clonal deciduous shrubs in North America and 1 species
      endemic to China. In North American tallgrass prairie, Symphoricarpos orbiculatus
      (buckbrush) is the dominant shrub often forming large colonies via sexual and
      asexual reproductive mechanisms. Symphoricarpos shrubs, in particular S.
      orbiculatus, use a unique sexual reproductive mechanism known as layering where
      vertical stems droop and the tips root upon contact with the soil. Because of
      conflicting societal values of S. orbiculatus for conservation and agriculture
      and the current attempt to restore historical fire regimes, there is a need for
      basic research on the biological response of S. orbiculatus to anthropogenic
      burning regimes. RESULTS: From 2007 through 2013 we applied prescribed fires in
      the late dormant season on grazed pastures in the Grand River Grasslands of Iowa.
      From 2011 to 2013, we measured how S. orbiculatus basal resprouting and layering
      stems were affected by patchy fires on grazed pastures, complete pasture fires on
      grazed pastures or fire exclusion without grazing for more than three years. We
      measured ramet height, ramet canopy diameter, stems per ramet, ramets per 100 m2,
      and probability of new layering stems 120 days after fire. Height in burned plots
      was lower than unburned plots but S. orbiculatus reached ~ 84% of pre-burn height
      120 days after fire. Stems per ramet were 2x greater in the most recently burned
      plots due to basal re-sprouting. Canopy diameter and density of ramets was not
      affected by time since fire, but burned pastures had marginally lower densities
      than plots excluded from fire (P = 0.07). Fire triggered new layering stems and
      no new layering stems were found in plots excluded from fire. CONCLUSIONS: The
      mechanisms of both basal sprouting and aerial layering after fire suggest S.
      orbiculatus is tolerant to dormant season fires. Furthermore, dormant season
      fires, regardless if they were patchy fires or complete pasture fires, did not
      result in mortality of S. orbiculatus. Dormant season fires can reduce S.
      orbiculatus structural dominance and maintain lower ramet densities but also
      trigger basal resprouting and layering.

PMID- 28510958
TI  - The blue fluorescent protein from Vibrio vulnificus CKM-1 is a useful reporter
      for plant research.
AB  - BACKGROUND: The mBFP is an improved variant of NADPH-dependent blue fluorescent
      protein that was originally identified from the non-bioluminescent pathogenic
      bacteria Vibrio vulnificus CKM-1. To explore the application of mBFP in plants,
      the mBFP gene expression was driven by one of the three promoters, namely, leaf
      specific (RbcS), hypoxia-inducible (Adh) or auxin-inducible (DR5) promoters, in
      different plant tissues such as leaves, roots and flowers under diverse
      treatments. In addition, the expressed mBFP protein was targeted to five
      subcellular compartments such as cytosol, endoplasmic reticulum, apoplast,
      chloroplast and mitochondria, respectively, in plant cells. RESULTS: When the
      mBFP was transiently expressed in the tobacco leaves and floral tissues of moth
      orchid, the cytosol and apoplast exhibited brighter blue fluorescence than other
      compartments. The recombinant mBFP-mS1C fusion protein exhibited enhanced
      fluorescence intensity that was correlated with more abundant RNA transcripts
      (1.8 fold) as compared with a control. In the root tips of horizontally grown
      transgenic Arabidopsis, mBFP could be induced as a reporter under hypoxia
      condition. Furthermore, the mBFP was localized to the expected subcellular
      compartments, except that dual targeting was found when the mBFP was fused with
      the mitochondria-targeting signal peptide. Additionally, the brightness of mBFP
      blue fluorescence was correlated with NADPH concentration. CONCLUSION: The NADPH
      dependent blue fluorescent protein could serve as a useful reporter in plants
      under aerobic or hypoxic condition. However, to avoid masking the mitochondrial
      targeting signal, fusing mBFP as a fusion tag in the C-terminal will be better
      when the mBFP is applied in mitochondria trafficking study. Furthermore, mBFP
      might have the potential to be further adopted as a NADPH biosensor in plant
      cells. Future codon optimization of mBFP for plants could significantly enhance
      its brightness and expand its potential applications.

PMID- 28510960
TI  - Ontogeny of the extrafloral nectaries of Vigna adenantha (Leguminosae, Phaseolae)
      and its relation with floral development.
AB  - BACKGROUND: The inflorescences of the genus Vigna Savi have extrafloral nectaries
      (EFNs) among the flowers whose origin is still unknown. The disposition, anatomy
      and morphology, as well as the ontogeny of the extrafloral nectaries (EFNs)
      associated with the inflorescences of Vigna adenantha (G.F.W. Meyer) Marechal,
      Mascherpa & Stainier (Leguminosae, Papilionoideae, Phaseolae) were studied.
      Besides, the ultrastructure of the secretory stage was described. RESULTS: The
      inflorescence, a raceme, bears a brief globose secondary axis in each node with 2
      flowers and 5-7 EFNs, which develop in acropetal direction. Each EFN originates
      from the abscission of a flower bud that interrupts its development, resulting in
      an elevated EFN. This secretory structure is formed by a ring of epidermal and
      parenchymatic cells surrounding a group of elongated central cells. The nectary
      is irrigated by phloem and xylem. Four developmental stages proceed; each one
      relates to a different embryological stage of the flowers in each secondary axis.
      CONCLUSIONS: The first functional EFN of each secondary axis of the inflorescence
      reaches its maturity when both the pollen grains and the embryo sacs are
      completely developed and the flowers begin to open. The secretion is
      granulocrine. The following EFNs develop in the same way.

PMID- 28510961
TI  - Chlorophyll and carbohydrate metabolism in developing silique and seed are
      prerequisite to seed oil content of Brassica napus L.
AB  - BACKGROUND: Although the seed oil content in canola is a crucial quality
      determining trait, the regulatory mechanisms of its formation are not fully
      discovered. This study compared the silique and seed physiological
      characteristics including fresh and dry weight, seed oil content, chlorophyll
      content, and carbohydrate content in a high oil content line (HOCL) and a low oil
      content line (LOCL) of canola derived from a recombinant inbred line in 2010,
      2011, and 2012. The aim of the investigation is to uncover the physiological
      regulation of silique and seed developmental events on seed oil content in
      canola. RESULTS: On average, 83% and 86% of silique matter while 69% and 63% of
      seed matter was produced before 30 days after anthesis (DAA) in HOCL and LOCL,
      respectively, over three years. Furthermore, HOCL exhibited significantly higher
      fresh and dry matter at most developmental stages of siliques and seeds. From 20
      DAA, lipids were deposited in the seed of HOCL significantly faster than that of
      LOCL, which was validated by transmission electron microscopy, showing that HOCL
      accumulates considerable more oil bodies in the seed cells. Markedly higher
      silique chlorophyll content was observed in HOCL consistently over the three
      consecutive years, implying a higher potential of photosynthetic capacity in
      siliques of HOCL. As a consequence, HOCL exhibited significantly higher content
      of fructose, glucose, sucrose, and starch mainly at 20 to 45 DAA, a key stage of
      seed lipid deposition. Moreover, seed sugar content was usually higher than
      silique indicating the importance of sugar transportation from siliques to seeds
      as substrate for lipid biosynthesis. The much lower silique cellulose content in
      HOCL was beneficial for lipid synthesis rather than consuming excessive
      carbohydrate for cell wall. CONCLUSIONS: Superior physiological characteristics
      of siliques in HOCL showed advantage to produce more photosynthetic assimilates,
      which were highly correlated to seed oil contents.

PMID- 28510962
TI  - How do leaf anatomies and photosynthesis of three Rhododendron species relate to
      their natural environments?
AB  - BACKGROUND: Rhododendron is one of the most well-known alpine flowers. In order
      to identify performances relating to Rhododendron's natural habitats we
      investigated the leaf anatomical structures and photosynthetic characteristics of
      R. yunnanense, R. irroratum and R. delavayi, which showed different responses
      after being transplanted into a common environment. RESULTS: When compared with
      R. irroratum and R. delavayi, R. yunnanense had lower leaf dry mass per unit area
      (LMA) and larger stomata, but smaller stomatal density (SD) and total stomata
      apparatus area percent (At), lower stomatal conductance (Gs), transpiration rate
      (Tr), light compensation point (LCP), light saturation point (LSP), light
      saturated photosynthetic rate (Amax) and leaf nitrogen content per unit area
      (Na). LMA was positively correlated with Amax and maximum rates of carboxylation
      (Vcmax). However, leaf N content was not significantly correlated with Amax.
      Thus, the variation in leaf photosynthesis among species was regulated largely by
      changes in LMA, rather than the concent of nitrogen in leaf tissue. CONCLUSIONS:
      R. yunnanense plants are vulnerable to moisture and light stress, while R.
      irroratum and R. delavayi are better suited to dry and high radiation
      environments. The present results contribute to our understanding physiological
      trait divergence in Rhododendron, as well benefit introduction and domestication
      efforts for the three species of Rhododendron studied in this work.

PMID- 28510964
TI  - Occurrence, types and distribution of calcium oxalate crystals in leaves and
      stems of some species of poisonous plants.
AB  - BACKGROUND: Calcium oxalate crystals, which are found in many organs of plants,
      have different morphological forms: as druses, prism, styloids, raphides and
      crystal sand. In this study, the distribution, type and specific location of
      calcium oxalate crystals in the leaves and stems of the eight species of
      poisonous plants and one species of nonpoisonous plant were investigated with
      light microscopy. During study special attention was given to the possible
      correlation between the presence and types of calcium oxalate crystals and toxic
      plant organs. The plants examined in this study were Hedera helix L.
      (Araliaceae), Aristolochia clematitis L. (Aristolochiaceae), Humulus lupulus L.
      (Cannabaceae), Saponaria officinalis L. (Caryophyllaceae), Chelidonium majus L.
      (Papaveraceae), Hypericum perforatum L. (Hypericaceae), Tribulus terrestris L.
      (Zygophyllaceae), Cynanchum acutum L. (Asclepiadaceae), and Nerium oleander L.
      (Apocynaceae). RESULTS: Three types of crystals: druses, prismatic crystals and
      crystal sands were observed. Druses were identified in the leaves and stems of
      six species of studied plants. In contrast to druses, crystal sands and prismatic
      crystals were rare. Prismatic crystals were observed in the leaf mesophlly cells
      of both Nerium oleander and Cynanchum acutum. However, crystal sands were
      observed only in the pith tissue of Humulus lupulus. On the other hand, leaves
      and stems of Chelidonium majus, Aristolochia clematitis and Hypericum perforatum
      were devoid of crystals. CONCLUSION: There is no absolute correlation between the
      presence and type of calcium oxalate crystals and toxic plant organs. However
      druse crystals may function as main irritant in toxic organs of the plants.

PMID- 28510963
TI  - How plants cope with heavy metals.
AB  - Heavy metals are naturally occurring in the earth's crust but anthropogenic and
      industrial activities have led to drastic environmental pollutions in distinct
      areas. Plants are able to colonize such sites due to several mechanisms of heavy
      metal tolerance. Understanding of these pathways enables different fruitful
      approaches like phytoremediation and biofortification.Therefore, this review
      addresses mechanisms of heavy metal tolerance and toxicity in plants possessing a
      sophisticated network for maintenance of metal homeostasis. Key elements of this
      are chelation and sequestration which result either in removal of toxic metal
      from sensitive sites or conduct essential metal to their specific cellular
      destination. This implies shared pathways which can result in toxic symptoms
      especially in an excess of metal. These overlaps go on with signal transduction
      pathways induced by heavy metals which include common elements of other signal
      cascades. Nevertheless, there are specific reactions some of them will be
      discussed with special focus on the cellular level.

PMID- 28510965
TI  - Salt tolerance mechanisms in Salt Tolerant Grasses (STGs) and their prospects in
      cereal crop improvement.
AB  - Increasing soil salinity in the agricultural fields all over the world is a
      matter of concern. Salinity poses a serious threat to the normal growth and
      development of crop plants. What adds to the concern is that all the cereal crops
      are sensitive to increasing soil salinity. So it is implacable to either search
      for salinity resistant varieties of crop plants or transform them genetically to
      sustain growth and reproducibility at increasing salinity stress. For the second
      perspective, mining the salt tolerant genes in the close relatives of cereal
      crops apparently becomes important, and most specifically in the salt tolerant
      grasses (STGs). STGs include the halophytes, facultative halophytes and salt
      tolerant glycophytes of the family Poaceae. In this review the potentiality of
      STGs has been evaluated for increasing the salinity tolerance of cereal crops.
      STGs are capable of surviving at increasing salt stress by utilizing different
      mechanisms that include vacuolization of toxic Na+ and Cl- in mature or senescing
      leaves, secretion of excess salts by salt glands, accumulation of osmolytes like
      proline and glycine betaine, and scavenging of ROS by antioxidative enzymes. The
      STGs are a therefore a potent source of salt tolerant genes.

PMID- 28510966
TI  - From leaf and branch into a flower: Magnolia tells the story.
AB  - BACKGROUND: In the classical doctrines, Magnolia was frequently considered the
      archetype among flowering plants, and its conduplicate carpel with marginal
      placentation was assumed to be derived from a leaf-like organ bearing ovules
      along its margins. Although the robustness of this concept has been seriously
      questioned by advances in botanical research, especially the emergence of
      Magnolia deeper in the angiosperm tree of life in molecular systematics, it
      remains the most-taught interpretation for the origin of carpels. RESULTS: To
      test the validity of this classical doctrine, we performed comparative anatomical
      analyses of the vascular bundles in the flowers of Magnolia using fine (8-MUm)
      paraffin -sections. We document the presence of two independent vascular systems
      in the carpels: the collateral bundles of the dorsal and ventral veins arising
      from the stelar bundle, and the amphicribral ovular bundles arising from the
      cortical bundles. This observation in conjunction with data from other fields
      concurrently suggests that the ovary wall is equivalent to a foliar organ whereas
      the placenta represents an ovule-bearing shoot. CONCLUSIONS: Our observation on
      the former model plant, Magnolia, nullifies the classical doctrine of carpel
      evolution and supports the Unifying Theory. This conclusion prompts a
      reconsideration of the concept of angiosperm flower evolution.

PMID- 28510967
TI  - Characterization of a fungicidal substance produced by Eupenicillium brefeldianum
      isolated from soil for plant disease control and its significance in nature.
AB  - BACKGROUND: A fungus identified as Eupenicillium brefeldianum was isolated from
      soil amended with vegetable tissues. RESULT: When grown in liquid medium prepared
      from the same vegetable tissues, E. brefeldianum produced a substance capable of
      preventing disease development of leaf spots of mustard cabbage caused by
      Alternaria brassicicola and inhibiting the germination of A. brassicicola
      conidia. The inhibitory substance was fungicidal and was very stable under high
      temperature and extreme pH. It was soluble in polar solvents but not soluble in
      non-polar solvents, and did not have charges on its molecule. This is the first
      discovery of the production of a fungicidal substance by this fungus. CONCLUSION:
      Results from this study suggest the possession of a strong competitive
      saprophytic ability by E. brefeldianum, which in turn may explain the widespread
      occurrence of this fungus in soils.

PMID- 28510968
TI  - Multiple resistance-activating substances produced by Humicola phialophoroides
      isolated from soil for control of Phytophthora blight of pepper.
AB  - BACKGROUND: Microorganisms capable of utilizing vegetable tissues for
      multiplication in soil were isolated, cultivated in liquid medium prepared from
      the same vegetable tissues, and tested for ability to activate resistance in
      pepper leaves against Phytophthora blight caused by Phytophthora capsici.
      RESULTS: Among the 121 microorganisms isolated, a fungus Humicola phialophoroides
      showed distinct ability to produce substances capable of activating resistance.
      The resistance-activating substances produced by H. phialophoroides were mostly
      retained in the mycelium, and were readily extracted from the mycelium powder
      with polar solvents. The extract was not inhibitory to zoospore germination or
      germ tube growth of P. capsici. In pepper leaves, the extract took only about 12
      h to activate resistance against P. capsici. After activation, washing treated
      leaf surface with water did not have much effect on the resistance expression. In
      addition to being able to move from the upper leaf surface to lower leaf surface,
      the resistance-activating substances were capable of moving 5 mm acropetally and
      10 mm basipetally in pepper leaves, Chromatography of the extract on silica gel
      column suggests that there are probably more than three components in the extract
      with resistance-activating ability. The resistance-activating activity of the
      mycelium extract was not affected by treatment with either cation or anion
      exchange resins, indicating that none of the active components have positive or
      negative charges on their molecules. CONCLUSION: Results show that H.
      phialophoroides is capable of producing multiple resistance-activating substances
      which are mostly retained in the mycelium. The study also indicates that none of
      the active components have positive or negative charges on their molecules.

PMID- 28510971
TI  - Construction of a high-quality genomic BAC library for Chinese peanut cultivar
      Zhonghua 8 with high oil content.
AB  - BACKGROUND: Arachis hypogaea L. (2n = 4* = 40, AABB) is one of the most important
      oil and economic crop plants in the word. This species has the largest genome
      size of about 2,813 Mb among the oil crop species. Zhonghua 8 is a peanut
      cultivar planted widely in central China and has several superior traits
      including high oil content, high yield and disease resistance. A high-quality BAC
      library of Zhonghua 8 was constructed for future researches on the genomics of
      Chinese peanut cultivars. RESULTS: A Hin d III-digested genomic BAC (bacterial
      artificial chromosome) library was constructed with the genomic DNA from leaves
      of Zhonghua 8. This BAC library consists of 160,512 clones and the average insert
      is estimated about 102 kb ranging from 30 to 150 kb. The library represents about
      5.55* haploid genome equivalents, and provides a 99.71% probability of finding
      specific genes. The empty-vector rate is under 5 percent detected from 200
      randomly selected clones. Probing of 384 clones with the psbA gene of barley
      chloroplast and the atp6 gene of rice mitochondrion indicated that the
      contamination with organellar DNA is insignificant. Successive subculture of
      three clones showed that the inserts are stable in one hundred generations.
      CONCLUSIONS: This study presented the construction of a high-quality BAC library
      for the genome of Chinese cultivated peanut. Many essential experiences were
      summarized in the present study. This BAC library can serve as a substantial
      platform for development of molecular marker, isolation of genes and further
      genome research.

PMID- 28510970
TI  - Inhibition of ABA-induced stomatal closure by fusicoccin is associated with
      cytosolic acidification-mediated hydrogen peroxide removal.
AB  - BACKGROUND: Fusicoccin (FC), a fungal phytotoxin produced by Fusicoccum amygdale,
      causes the inhibition of ABA-induced stomatal closure. The mechanism of
      inhibition is remaining unclear. We analyzed the role of hydrogen peroxide (H2O2)
      and relationship between H2O2 removal and cytosolic pH changes during inhibition
      of ABA-induced stomatal closure by FC. RESULTS: According to the results, ABA
      treatment induced H2O2 production and stomatal closure, but FC inhibited the
      effects of ABA on these two parameters. Treatment with catalase (CAT) and NADPH
      oxidase inhibitor diphenylene iodonium (DPI) mimicked the effect of FC. These
      data suggest that inhibition of ABA effect by FC is related to the decrease of
      H2O2 levels in guard cells. Furthermore, similar to CAT, FC not only suppressed
      stomatal closure and H2O2 levels in guard cells treated with exogenous H2O2, but
      also reopened the stomata which had been closed by ABA and reduced the level of
      H2O2 that had been produced by ABA, indicating that FC causes H2O2 removal in
      guard cells. The butyric acid treatment simulated the effects of FC on the
      stomatal aperture and H2O2 levels in guard cells treated with exogenous H2O2 and
      had been closed by ABA, and both FC and butyric acid reduced cytosolic pH in
      guard cells of stomata treated with H2O2 and had been closed by ABA, which
      demonstrate that cytosolic acidification mediates FC-induced H2O2 removal.
      CONCLUSION: These results suggest that FC causes cytosolic acidification in guard
      cells, then induces H2O2 removal and reduces H2O2 levels in guard cells, finally
      inhibits stomatal closure induced by ABA.

PMID- 28510972
TI  - Floral development of Dieffenbachia and the occurrence of atypical flowers in
      Araceae.
AB  - BACKGROUND: The floral development of Dieffenbachia seguine (N. J. Jacquin)
      Schott is analysed in relation to the molecular phylogeny of the Spathicarpae by
      Cusimano et al. (Am J Bot 98:654-668, 2011). RESULTS: The initiation of discoid
      floral primordia occurs acropetally on the surface of the spadix. Female flowers,
      atypical bisexual flowers, sterile male flowers, and male flowers share the same
      phyllotactic spirals on the spadix. Four or five stamen primordia are initiated
      simultaneously on the periphery of the male floral meristem. During early stages
      of stamen initiation, individual stamen primordia are connate at their base. In a
      synandrium, stamen fusion occurs very early during their developmental cycle with
      the stamens being already united laterally when longitudinal elongation occurs.
      The staminodes are also initiated on the periphery of the discoid floral
      primordium, and their number varies from four to six. The development of the
      fused staminodes will eventually form a longitudinal cavity in the center of the
      mature synandrode. The atypical flowers located in the intermediate zone range in
      morphology from aborted female flowers to rudimentary sterile male flowers with
      incomplete staminodes. CONCLUSIONS: The development of the female flower of
      Dieffenbachia Schott presents some similarities with atypical bisexual flowers of
      Cercestis Schott representing one of three types of aberrant flower forms in the
      family. From a developmental point of view and in the context of a phylogeny of
      the group, we believe that the presence of staminodes in the female zone
      constitutes a plesiomorphy in the tribe Spathicarpeae.

PMID- 28510969
TI  - Role of L-ascorbate in alleviating abiotic stresses in crop plants.
AB  - L-ascorbic acid (vitamin C) is a major antioxidant in plants and plays a
      significant role in mitigation of excessive cellular reactive oxygen species
      activities caused by number of abiotic stresses. Plant ascorbate levels change
      differentially in response to varying environmental stress conditions, depending
      on the degree of stress and species sensitivity. Successful modulation of
      ascorbate biosynthesis through genetic manipulation of genes involved in
      biosynthesis, catabolism and recycling of ascorbate has been achieved. Recently,
      role of ascorbate in alleviating number of abiotic stresses has been highlighted
      in crop plants. In this article, we discuss the current understanding of
      ascorbate biosynthesis and its antioxidant role in order to increase our
      comprehension of how ascorbate helps plants to counteract or cope with various
      abiotic stresses.

PMID- 28510973
TI  - Potential preventive role of Iranian Achillea wilhelmsii C. Koch essential oils
      in acetaminophen-induced hepatotoxicity.
AB  - BACKGROUND: The essential oil of Achillea wilhelmsii C. Koch (100 & 200 mg/kg
      b.w, i.p) was evaluated against acetaminophen induced hepatic injuries in rats.
      For this purpose, the activities of cytochrome P450 (CYP450), glutathione s
      transferase (GST) and markers of liver injuries (ALT, AST, ALP) together with
      level of GSH measured analytically in time intervals (2, 4, 8, 16 & 24 h) after
      treatments confirmed by histophatological consideration in rat livers. RESULTS:
      Administration of acetaminophen (500 mg/kg bw, i.p) significantly increased the
      activity of CYP450 concomitant with increasing the release of ALT and AST.
      Whereas, GSH level and GST activity were decreased significantly after
      acetaminophen treatment. Treatment of rats with Achillea wilhelmsii essential
      oils significantly modulate these parameters to normal values. Also,
      histophatological analysis of liver biopsies was consistent with the biochemical
      findings. CONCLUSION: The data led us to conclude the curative potential of
      Achillea wilhelmsii essential oils against APAP induced hepatic injuries.

PMID- 28510974
TI  - Differentiation between two strains of microalga Parachlorella kessleri using
      modern spectroscopic method.
AB  - BACKGROUND: The differentiation between wild type of Parachlorella kessleri and
      its mutant strains PC Mut2, PC Mut4 by using the Multi-functional Plant
      Efficiency Analyzer (M-REA-2) was studied. Mutant algal cells of P. kessleri have
      been obtained by UV-C during 3 and 10 min respectively. RESULTS: Light-induced
      kinetics of prompt fluorescence (OJIP transients), delayed fluorescence and
      modulated reflection at 820 nm (redox transitions of P700 in PSI) showed
      disturbance of electron transport flow in photosystem II (PSII) and an increase
      fraction of non-reducing centers of secondary quinone acceptors of electron (QB).
      In addition, the amplitudes of the fast and slow peak in the kinetics of the
      delayed light emission and non-photochemical fluorescence quenching ( NPQ) were
      significantly reduced in mutant cells, indicating low level of the membrane
      energization of photosynthetic membranes. Changes of photosynthetic reactions of
      mutants may lead to an increase of the carotenoids content, which protect cells
      against the light stress. CONCLUSION: It is suggested to use parameters of
      induction curves of prompt and delayed fluorescence to characterize mutant algal
      cells in biotechnological studies.

PMID- 28510975
TI  - In vitro propagation of Gentiana scabra Bunge - an important medicinal plant in
      the Chinese system of medicines.
AB  - BACKGROUND: Gentiana scabra Bunge commonly known as 'Long dan cao' in China has
      been used in traditional Chinese medicines for more than 2000 years. Dry roots
      and rhizome of the herb have been used for the treatment of inflammation,
      anorexia, indigestion and gastric infections. Iridoids and secoiridoids are the
      main bioactive compounds which attribute to the pharmacological properties of
      this plant. The species is difficult to mass propagate by seed due to the low
      percentage of germination and limited dormancy period. Wild populations in some
      locations are considered to be in the endangered category due to over
      exploitation. RESULTS: In the present study, we report an efficient
      micropropagation system. Shoot apices of six weeks old in vitro grown G. scabra
      plants were used as explants for the in vitro propagation. Induction of multiple
      shoots (9.1/explant) was achieved on the culture of shoot apices on half strength
      Murashige and Skoog's basal medium (MSBM) containing 2.0 mg/L-1 6
      benzylaminopurine (BA), 3% sucrose and 0.9% Difco agar. In vitro shoots induced
      profuse rooting on half strength of MSBM supplemented with 0.1 mg/L-1 1
      naphthaleneacetic acid (NAA), 3% sucrose and 0.3% gelrite. A two-stage
      ventilation closure procedure during the in vitro culture, and transparent sachet
      technique enhanced the survival rate of G. scabra plantlets to 96% in the
      greenhouse. Tissue culture plants flowered after 5 months of transfer to pots.
      CONCLUSIONS: A simple and an efficient in vitro propagation protocol of Gentiana
      scabra Bunge by optimizing the medium composition and ventilation closure
      treatments has been developed. The protocol can be very useful in germplasm
      conservation and commercial cultivation of G. scabra plants.

PMID- 28510976
TI  - Effects of salt stress on antioxidant defense system in the root of Kandelia
      candel.
AB  - BACKGROUND: This study aimed to explore the active oxygen scavenging mechanism of
      Kandelia candel, in order to provide a theoretical basis for further analysis on
      the physiological mechanism of salt tolerance in mangrove plants. Different
      concentrations of NaCl solution (0, 150, 300 and 450 mmol/L) were used for salt
      stress treatments on Kandelia candel, physiological indicators in the root of
      Kandelia candel were measured in different processing time. RESULTS: With the
      increase of salt concentrations and processing time, the contents of total
      proteins in the root of Kandelia candel were reduced; the CAT activity, SOD
      activity, ASA content and MDA content all had decreased with the increase of salt
      concentrations and shown a trend from ascent to descent with the increase of
      processing time, the peak of ASA and MDA contents were observed at 6 h, that of
      SOD activity was observed at 9 h and that of CAT activity was at 12 h; POD
      activity had shown an overall upward trend with the increase of salt
      concentrations and processing time, which reached the maximum at 24 h; the
      variations of these physiological indicators were more significant in high
      concentrations of NaCl solution (450 mmol/L). CONCLUSIONS: A certain salt
      concentration (<300 mmol/L) was required for the growth of Kandelia candel
      seedlings. At the early stage of high-salt stress, Kandelia candel can rapidly
      activate antioxidant defense system to resist the salt induced oxidative stress,
      thus reducing the damages of oxidative stress to plasma membrane, which might be
      an effective means for Kandelia candel to resist high salt stress.

PMID- 28510978
TI  - Overexpression of a SNARE protein AtBS14b alters BR response in Arabidopsis.
AB  - BACKGROUND: N-ethyl-maleimide sensitive factor adaptor protein receptor (SNAREs)
      domain-containing proteins were known as key players in vesicle-associated
      membrane fusion. Genetic screening has revealed the function of SNAREs in
      different aspects of plant biology, but the role of many SNAREs are still
      unknown. In this study, we have characterized the role of Arabidopsis Qc-SNARE
      protein AtBS14b in brassinosteroids (BRs) signaling pathway. RESULTS: AtBS14b
      overexpression (AtBS14b ox) plants exhibited short hypocotyl and petioles lengths
      as well as insensitivity to exogenously supplied BR, while AtBS14b mutants did
      not show any visible BR-dependent morphological differences. BR biosynthesis
      enzyme BR6OX2 expression was slightly lower in AtBS14b ox than in wild type
      plants. Further BR-mediated repression of BR6OX2, CPD and DWF4 was inhibited in
      AtBS14b ox plants. AtBS14b-mCherry fusion protein localized in vesicular
      compartments surrounding plasma membrane in N. benthamiana leaves. In addition,
      isolation of AtBS14b-interacting BR signaling protein, which localized in plasma
      membrane, showed that AtBS14b directly interacted with membrane steroid binding
      protein 1 (MSBP1), but did not interact with BAK1 or BRI1. CONCLUSION: These data
      suggested that Qc-SNARE protein AtBS14b is the first SNARE protein identified
      that interacts with MSBP1, and the overexpression of AtBS14b modulates BR
      response in Arabidopsis.

PMID- 28510977
TI  - Exogenous spermidine-induced changes at physiological and biochemical parameters
      levels in tomato seedling grown in saline-alkaline condition.
AB  - BACKGROUND: Tomato is one of the most popular vegetables, and middle tolerance
      for salt stress. Spermidine (Spd) has an important role in plant defense
      mechanisms against abiotic stress; however, relatively few data are available
      regarding Spd in responses of tomato to saline-alkaline stress. The effect of
      0.25 mmol/L Spd on some physiological parameters of two tomato cultivars grown in
      75 mmol/L saline-alkaline solutions were studied. Two cultivars are cv. Jinpeng
      chaoguan which is a highly salt-tolerant ecotype and cv. Zhongza No. 9 which is
      more salt-sensitive ecotype. RESULTS: Saline-alkaline stress upset nitrogen
      metabolism, induced the antioxidant enzyme activities, and accumulated much more
      reactive oxygen species (ROS) and osmoregulation substances in two tomato
      cultivars leaves. Under saline-alkaline stress condition, Spd-treated seedlings
      accumulated more osmoregulation substances and had greater activities of
      antioxidative enzymes. Exogenous Spd counteracted the stress-induced increase of
      contents of malondialdehyde and ammonium, glutamate dehydrogenase activity, and
      decreased in nitrate, nitrate reductase, nitrite reductase, glutamine synthetase,
      glutamate synthase, glutamate oxaloacetate transaminase, and glutamate pyruvate
      transaminase activities. Additionally, the effect of Spd was more significantly
      in salt-sensitive cultivar 'Zhongza No. 9'. CONCLUSIONS: Overall, exogenous
      spermidine can attenuate negative effects of saline-alkaline stress on tomato
      seedlings which effects may depend on the plant species, and even cultivars.

PMID- 28510979
TI  - Isolation and identification of a phytotoxic substance from the emergent
      macrophyte Centrostachys aquatica.
AB  - BACKGROUND: Centrostachys aquatica is a perennial emergent macrophyte in marshy
      places and in rivers. The species was recorded in Senegal and Nigeria, but
      widespread in tropical Africa, and South and East Asia. Aqueous methanol extracts
      C. aquatica was found to be toxic to several plant species. However, no
      phytotoxic substance has been reported in this species. Therefore, we
      investigated phytotoxic activity and searched for phytotoxic substances with
      allelopathic activity in C. aquatica. RESULTS: An aqueous methanol extract of C.
      aquatica inhibited the growth of roots and hypocotyls of cress (Lepidium
      sativum). The extract was then purified by several chromatographic runs and a
      phytotoxic substance with allelopathic activity was isolated and identified by
      spectral analysis as loliolide. Loliolide inhibited cress root and hypocotyl
      growth at concentrations greater than 0.03 MUM. The concentrations required for
      50% growth inhibition of cress roots and hypocotyls was 0.18 and 0.15 MUM,
      respectively. CONCLUSION: These results suggest that loliolide is a phytotoxic
      substance and may contribute to the allelopathic effect caused by C. aquatica.

PMID- 28510980
TI  - Begonia jinyunensis (Begoniaceae, section Platycentrum), a new palmately compound
      leaved species from Chongqing, China.
AB  - BACKGROUND: Continental China is the center of Begonia species diversity in Asia
      and contains more than 60 species out of about 110 named species of section
      Platycentrum. Mt. Jinyun, located in Chongqing City at the upper reaches of the
      Yangtze River, harbors a subtropical broadleaved forest with high species
      diversity. During a botanical survey in Mt. Jinyun, an unknown Begonia species of
      sect. Platycentrum with palmately compound leaves was collected and studied based
      on detailed morphological observations and cytological and molecular phylogenetic
      analyses. RESULTS: The unknown Begonia bears a superficial resemblance to B.
      hemsleyana in having palmately compound leaves, a feature unseen in other species
      of sect. Platycentrum in China. It is however sharply distinct from the latter in
      the acaulous habit with aerial stems seen only at anthesis and long rhizomes (vs.
      erect stems to 70 cm or taller with short rhizomes), 4-6 pinnatilobed leaflets
      with indistinct, decurrent petiolules (vs. 7-10 serrate leaflets with distinct
      petiolules), and white (vs. pink) tepals. Molecular phylogenetic analyses based
      on nuclear ribosomal DNA and chloroplast DNA sequences indicated that this
      species was allied to Platycentrum species occurring in Southwest and South
      central China and Vietnam, including B. hemsleyana, and clearly separable from
      these species. Somatic chromosome number of 2n = 22 was reported for this unknown
      species. The diploid chromosome number is agreeable with those published for
      Begonia sect. Platycentrum. CONCLUSIONS: The unknown Begonia is confirmed to be a
      new species of sect. Platycentrum and hereto described as Begonia jinyunensis C.
      I Peng, B. Ding & Q. Wang.

PMID- 28510981
TI  - Effect of phosphorus deficiency on photosynthetic inorganic carbon assimilation
      of three climber plant species.
AB  - BACKGROUND: P deficiency in karst areas significantly influenced leaf
      photosynthesis and carbon metabolisms in plants which were bad for plant growth.
      Meanwhile, fertilizer application would cause lots of environmental problems.
      Therefore planning and developing P deficiency-resistant plants in karst areas
      are important to prevent shortage of P resources and reduce the environmental
      impacts of P supplementation. RESULTS: This study examined the photosynthetic
      response of three climber plant species, namely, Pharbitis nil (Linn.) Choisy,
      Lonicera pampaninii Levl, and Parthenocissus tricuspidata (Sieb.et Zucc.) Planch
      to phosphorus (P) deficiency stress. The plants were exposed to P deficiency
      stress at three treatments of 0.125 mM, 0.031 mM, and 0 mM for 30 d; 0.250 mM P
      was used as the control. Photosynthetic responses were determined by measurement
      of leaf photosynthesis, chlorophyll fluorescence, carbonic anhydrase activity,
      and stable carbon isotope ratios. Pharbitis nil showed high CA activity, more
      negative delta13C values and could maintain long-term stable photosynthetic
      capacity. Lonicera pampaninii also showed high CA activity but positive delta13C
      values compared to Pharbitis nil, and its photosynthetic capacity decreased as P
      deficiency stress increased. Parthenocissus tricuspidata had a low photosynthesis
      and positive delta13C values compared to Pharbitis nil, it could grow normally
      even under 0 mM P. CONCLUSIONS: Pharbitis nil was tolerant to long-term, severe P
      deficiency stress, a finding that is attributed to its stable PSII and regulation
      of carbonic anhydrase. Lonicera pampaninii showed a poor adaptability to short
      term P deficiency, but exhibited long-term tolerance under 0.125 mM P
      concentration. Parthenocissus tricuspidata was tolerant to long-term P deficiency
      stress, may exhibit a stomatal limitation. Besides, P deficiency stress had
      little effect on the way of inorganic carbon utilization of the three climber
      plants. Different adaptation mechanisms to P deficiency stress should be
      considered for the selection of species when developing P deficiency-resistant
      plants.

PMID- 28510982
TI  - Immunolocalization of chromosome-associated proteins in plants - principles and
      applications.
AB  - The use of the immunolocalization technique combined with cytogenetic and
      epigenetic studies is an indispensable tool and has contributed significantly to
      the analysis of the structure and function of chromosomes, since it can provide
      information about the spatial or temporal distribution of a given protein in the
      nucleus and chromosomes. Several chromosome-associated proteins in plant cells
      have already been identified by immunolocalization, such as histone and non
      histone proteins and cell division-related protein (mitosis and meiosis). The
      principle of the immunolocalization technique in plants basically involves
      fixation and permeabilization of cells, the use of monoclonal or polyclonal
      antibodies attached to a signaling molecule, usually a fluorochrome and detection
      of the target molecule by using an epifluorescence microscope.

PMID- 28510983
TI  - Effects of cadmium on lipids of almond seedlings (Prunus dulcis).
AB  - BACKGROUND: Cadmium uptake and distribution, as well as its effects on lipid
      composition was investigated in almond seedlings (Prunus dulcis) grown in culture
      solution supplied with two concentrations of Cd (50 and 150 MUM). RESULTS: The
      accumulation of Cd increased with external metal concentrations, and was
      considerably higher in roots than in leaves. Fourteen days after Cd treatment,
      the membrane lipids were extracted and separated on silica-gel thin layer
      chromatography (TLC). Fatty acid methyl esters were analyzed by FID-GC on a
      capillary column. Our results showed that Cd stress decreased the quantities of
      all lipids classes (phospholipids, galactolipids and neutral lipids).
      Galactolipid, phospholipid and neutral lipid concentrations decreased more in
      roots than in leaves by Cd-treatment. In almost all lipid classes the proportion
      of palmitic acid (16:0), linoleic (18: 2) and that of linolenic (18: 3) acid
      decreased, suggesting that heavy metal treatment induced an alteration in the
      fatty acid synthesis processes. CONCLUSIONS: In conclusion, our results show that
      the changes found in total fatty acids, in the quantities of all lipids classes,
      and in the in the profiles of individual polar lipids suggest that membrane
      structure and function might be altered by Cd stress.

PMID- 28510984
TI  - An active Catharanthus roseus desacetoxyvindoline-4-hydroxylase-like gene and its
      transcriptional regulatory profile.
AB  - BACKGROUND: Desacetoxyvindoline-4-hydroxylase is a key enzyme in the biosynthesis
      of vindoline, the important intermediate leading to vinblastine and vincristine
      in Catharanthus roseus. RESULTS: A d4h-like gene has been isolated from C. roseus
      C20hi cells based on an EST sequence from the Suppression Subtractive
      Hybridization cDNA library. The full length cDNA of d4h-like was 1427 bp encoding
      372 amino acids. It had 66% identities and 80% positives with d4h at the amino
      acid level. It belonged to 2-oxoglutarate dependent oxygenase superfamily as d4h
      did. Real-time quantitative PCR analysis revealed that d4h-like was expressed
      high in roots, flowers and C20hi cells, very low in leaves and stems. Methyl
      jasmonate could significantly increase the accumulation of d4h-like transcripts.
      2,4-D inhibited its expression. An approximate 2,910 bp of 5'-promoter region of
      d4h-like was obtained, fused to GUS reporter gene and analyzed with fluorescence
      quantitative assays using transient expression in C. roseus cell suspensions,
      indicating that d4h-like promoter could drive GUS gene expression in vivo.
      CONCLUSION: These results suggest that d4h-like is closely related with d4h in
      the genetic evolution but with different transcriptional expression profiles. It
      may be revolved in the hormone-independency of C20hi cells.

PMID- 28510985
TI  - Changing diagnosis coding routines may confound the results of longitudinal
      childhood pneumonia studies.
AB  - AIM: This Swedish study compared the discharge diagnosis codes used for children
      up to the age of five hospitalised for acute lower respiratory tract infections
      before and after the introduction of the pneumococcal conjugate vaccine in 2007.
      METHODS: The International Classification of Diseases-10th revision codes were
      used. We compared the discharge diagnosis codes at the Astrid Lindgren Children's
      Hospital from 1 July 2005 to 30 June 2007 (n=1,127) and 1 July 2011 to 30 June
      2013 (n=1,240) in relation to the diagnostic methods used. RESULTS: There was a
      54% reduction in the rate of all-cause pneumonia from the first to the second
      period in children aged 0-1 years, but some of this could have been due to the
      improved diagnosis of viral infections and us changing the code for respiratory
      syncytial virus infection from pneumonia to bronchiolitis. The overall rate of
      acute lower respiratory tract infections was unchanged. CONCLUSION: We could not
      determine how much of the reduction in bacterial pneumonia in children under one
      was because of the introduction of the pneumococcal conjugate vaccine, based
      solely on discharge codes. Longitudinal register studies should take changes in
      diagnosis codes into account.

PMID- 28510987
TI  - Iridium-Catalyzed Formyl-Selective Deuteration of Aldehydes.
AB  - We report the first direct catalytic method for formyl-selective deuterium
      labeling of aromatic aldehydes under mild conditions, using an iridium-based
      catalyst designed to favor formyl over aromatic C-H activation. A good range of
      aromatic aldehydes is selectively labeled, and a one-pot labeling/olefination
      method is also described. Computational studies support kinetic product control
      over competing aromatic labeling and decarbonylation pathways.

PMID- 28510988
TI  - Barriers to obstetric fistula treatment in low-income countries: a systematic
      review.
AB  - OBJECTIVE: To identify the barriers faced by women living with obstetric fistula
      in low-income countries that prevent them from seeking care, reaching medical
      centres and receiving appropriate care. METHODS: Bibliographic databases, grey
      literature, journals, and network and organisation websites were searched in
      English and French from June to July 2014 and again from August to November 2016
      using key search terms and specific inclusion and exclusion criteria for
      discussion of barriers to fistula treatment. Experts provided recommendations for
      additional sources. RESULTS: Of 5829 articles screened, 139 were included in the
      review. Nine groups of barriers to treatment were identified: psychosocial,
      cultural, awareness, social, financial, transportation, facility shortages,
      quality of care and political leadership. Interventions to address barriers
      primarily focused on awareness, facility shortages, transportation, financial and
      social barriers. At present, outcome data, though promising, are sparse and the
      success of interventions in providing long-term alleviation of barriers is
      unclear. CONCLUSION: Results from the review indicate that there are many
      barriers to fistula treatment, which operate at the individual, community and
      national levels. The successful treatment of obstetric fistula may thus require
      targeting several barriers, including depression, stigma and shame, lack of
      community-based referral mechanisms, financial cost of the procedure,
      transportation difficulties, gender power imbalances, the availability of
      facilities that offer fistula repair, community reintegration and the competing
      priorities of political leadership.

PMID- 28510986
TI  - Blood pressure normalization via pharmacotherapy improves cutaneous microvascular
      function through NO-dependent and NO-independent mechanisms.
AB  - : Hypertension is associated with endothelial dysfunction and vascular
      remodeling. OBJECTIVE: To assess effects of antihypertensive pharmacotherapy on
      eNOS- and iNOS-dependent mechanisms and maximal vasodilator capacity in the
      cutaneous microvasculature. METHODS: Intradermal microdialysis fibers were placed
      in 15 normotensive (SBP 111+/-2 mm Hg), 12 unmedicated hypertensive (SBP 142+/-2
      mm Hg), and 12 medicated hypertensive (SBP 120+/-2 mm Hg) subjects. Treatments
      were control, iNOS-inhibited (1400w), and NOS-inhibited (l-NAME). Red cell flux,
      measured during local heating (42 degrees C) and ACh dose-response protocols, was
      normalized to CVC (flux MAP-1 ) and a percentage of maximal vasodilation (%CVCmax
      ). RESULTS: Compared to normotensives, ACh-mediated vasodilation was attenuated
      in the hypertensive (P<.001), but not in medicated subjects (P=.83). NOS
      inhibition attenuated ACh-mediated vasodilation in normotensives compared to
      hypertensive (P<.001) and medicated (P<.001) subjects. With iNOS inhibition,
      there was no difference in ACh-mediated vasodilation between groups. Compared to
      the normotensives, local heat-induced vasodilation was attenuated in the
      hypertensives (P<.001), but iNOS inhibition augmented vasodilation in the
      hypertensives so this attenuation was abolished (P=.31). Compared to
      normotensives, maximal vasodilator capacity was reduced in the hypertensive
      (P=.014) and medicated subjects (P=.004). CONCLUSIONS: In the cutaneous
      microvasculature, antihypertensive pharmacotherapy improved endothelial function
      through NO-dependent and NO-independent mechanisms, but did not improve maximal
      vasodilator capacity.

PMID- 28510990
TI  - Perioperative nutrition management as an important component of surgical capacity
      in low- and middle-income countries.
AB  - Needs for surgical care are growing in low- and middle-income countries. Existing
      surgical care capacity indicators, focusing on the availability of equipment,
      personnel, and operation and anaesthetic skills, are not intended to evaluate
      perioperative nutrition management, which influences surgical outcomes. In this
      narrative review, we describe the prevalence of malnutrition and its clinical
      consequences among surgical patients in low- and middle-income countries, suggest
      potential measures to improve nutrition management and discuss the necessity of
      considering nutrition management as a component of surgical care capacity.

PMID- 28510989
TI  - Characterization of Brachyspira hyodysenteriae isolates from Italy by multilocus
      sequence typing and multiple locus variable number tandem repeat analysis.
AB  - AIMS: To evaluate and compare the capabilities of multilocus sequence typing
      (MLST) and multiple locus variable number tandem repeat analysis (MLVA)
      techniques to characterize Brachyspira hyodysenteriae isolates and to investigate
      the relationship between pleuromutilin resistance and genetic variability.
      METHODS AND RESULTS: MLST genotyping was performed on 180 B. hyodysenteriae
      isolates, and the results were evaluated considering profiles from 108 other
      strains previously reported in the database. In total, 37 sequence types were
      obtained. The MLVA approach completely characterized 172 strains and grouped the
      isolates into 22 different profiles. The combination of MLST and MLVA showed a
      slight increase in the discriminatory power, identifying 33 joint profiles. An
      antibiotic resistance analysis showed a reduction in the susceptibility to
      pleuromutilins over time, and a weak association between susceptibility to
      valnemulin and inclusion in clonal complex 4. CONCLUSION: MLST and MLVA are
      reliable methods for characterizing B. hyodysenteriae strains and they have
      comparable discriminatory power. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      genotyping of B. hyodysenteriae isolates and a database of all the genetic
      profiles collected during the diagnostic activities could support traditional
      epidemiological investigations in identifying infection sources and routes of
      transmission among herds, and in developing more effective control measures.

PMID- 28510991
TI  - Development of a panel of recombinase polymerase amplification assays for
      detection of common bacterial urinary tract infection pathogens.
AB  - AIMS: To develop and evaluate the performance of a panel of isothermal real-time
      recombinase polymerase amplification (RPA) assays for detection of common
      bacterial urinary tract infection (UTI) pathogens. METHODS AND RESULTS: The panel
      included RPAs for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis,
      Pseudomonas aeruginosa and Enterococcus faecalis. All five RPAs required reaction
      times of under 12 min to reach their lower limit of detection of 100 genomes per
      reaction or less, and did not cross-react with high concentrations of nontarget
      bacterial genomic DNA. In a 50-sample retrospective clinical study, the five-RPA
      assay panel was found to have a specificity of 100% (95% CI, 78-100%) and a
      sensitivity of 89% (95% CI, 75-96%) for UTI detection. CONCLUSIONS: The
      analytical and clinical validity of RPA for the rapid and sensitive detection of
      common UTI pathogens was established. SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid
      identification of the causative pathogens of UTIs can be valuable in preventing
      serious complications by helping avoid the empirical treatment necessitated by
      traditional urine culture's 48-72-h turnaround time. The routine and widespread
      use of RPA to supplement or replace culture-based methods could profoundly impact
      UTI management and the emergence of multidrug-resistant pathogens.

PMID- 28510993
TI  - Chiral separation of quinolones by liquid chromatography and capillary
      electrophoresis.
AB  - The quinolones are derivatives of oxoquinolines and mostly known for their
      antibacterial and antiviral activities. Many quinolones are chiral compounds
      having asymmetric centers and important due to their enantioselective biological
      activities. In order to study the biological activities of quinolone enantiomers,
      to control the manufacturing of homochiral drugs and to prepare necessary
      quantities of pure enantiomers for preclinical or clinical trials, respective
      chiral separation methods are urgently needed. In this context, the present
      review discusses chromatographic and electrophoretic methods for the
      enantioseparation of chiral quinolones and provides some useful information on
      their physical and pharmaceutical properties. The drawbacks of currently used
      techniques are revealed and ways to overcome them are outlined. Moreover,
      recommendations for an optimal choice of a separation protocol are given.

PMID- 28510994
TI  - Improved detection of Burkholderia pseudomallei from non-blood clinical specimens
      using enrichment culture and PCR: narrowing diagnostic gap in resource
      constrained settings.
AB  - OBJECTIVES: To evaluate the diagnostic utility of enrichment culture and PCR for
      improved case detection rates of non-bacteraemic form of melioidosis in limited
      resource settings. METHODS: Clinical specimens (n = 525) obtained from patients
      presenting at a tertiary care hospital of South India with clinical symptoms
      suggestive of community-acquired pneumonia, lower respiratory tract infections,
      superficial or internal abscesses, chronic skin ulcers and bone or joint
      infections were tested for the presence of Burkholderia pseudomallei using
      conventional culture (CC), enrichment culture (EC) and PCR. Sensitivity,
      specificity, positive and negative predictive values of CC and PCR were initially
      deduced using EC as the gold standard method. Further, diagnostic accuracies of
      all the three methods were analysed using Bayesian latent class modelling (BLCM).
      RESULTS: Detection rates of B. pseudomallei using CC, EC and PCR were 3.8%, 5.3%
      and 6%, respectively. Diagnostic sensitivities and specificities of CC and PCR
      were 71.4, 98.4% and 100 and 99.4%, respectively in comparison with EC as the
      gold standard test. With Bayesian latent class modelling, EC and PCR demonstrated
      sensitivities of 98.7 and 99.3%, respectively, while CC showed a sensitivity of
      70.3% for detection of B. pseudomallei. An increase of 1.6% (95% CI: 1.08-4.32%)
      in the case detection rate of melioidosis was observed in the study population
      when EC and/or PCR were used in adjunct to the conventional culture technique.
      CONCLUSIONS: Our study findings underscore the diagnostic superiority of
      enrichment culture and/or PCR over conventional microbiological culture for
      improved case detection of melioidosis from non-blood clinical specimens.

PMID- 28510992
TI  - Lymph node effective vascular permeability and chemotherapy uptake.
AB  - OBJECTIVE: Lymph node metastases are a poor prognostic factor. Additionally,
      responses of lymph node metastasis to therapy can be different from the primary
      tumor. Investigating the physiologic lymph node blood vasculature might give
      insight into the ability of systemic drugs to penetrate the lymph node, and thus
      into the differential effect of therapy between lymph node metastasis and primary
      tumors. Here, we measured effective vascular permeability of lymph node blood
      vessels and attempted to increase chemotherapy penetration by increasing
      effective vascular permeability. METHODS: We developed a novel three-dimensional
      method to measure effective vascular permeability in murine lymph nodes in vivo.
      VEGF-A was systemically administered to increase effective vascular permeability.
      Validated high-performance liquid chromatography protocols were used to measure
      chemotherapeutic drug concentrations in untreated and VEGF-A-treated lymph nodes,
      liver, spleen, brain, and blood. RESULTS: VEGF-A-treated lymph node blood vessel
      effective vascular permeability (mean 3.83 * 10-7  cm/s) was significantly higher
      than untreated lymph nodes (mean 9.87 * 10-8  cm/s). No difference was found in
      lymph node drug accumulation in untreated versus VEGF-A-treated mice.
      CONCLUSIONS: Lymph node effective vascular permeability can be increased
      (~fourfold) by VEGF-A. However, no significant increase in chemotherapy uptake
      was measured by pretreatment with VEGF-A.

PMID- 28510995
TI  - Native Mass Spectrometry from Common Buffers with Salts That Mimic the
      Extracellular Environment.
AB  - Nonvolatile salts are essential for the structures and functions of many proteins
      and protein complexes but can severely degrade performance of native mass
      spectrometry by adducting to protein and protein complex ions, thereby reducing
      sensitivity and mass measuring accuracy. Small nanoelectrospray emitters are used
      to form protein and protein complex ions directly from high-ionic-strength (>150
      mm) nonvolatile buffers with salts that mimic the extracellular environment.
      Charge-state distributions are not obtained for proteins and protein complexes
      from six commonly used nonvolatile buffers and >=150 mm Na+ with conventionally
      sized nanoelectrospray emitter tips but are resolved with 0.5 MUm tips. This
      method enables mass measurements of proteins and protein complexes directly from
      a variety of commonly used buffers with high concentrations of nonvolatile salts
      and eliminates the need to buffer exchange into volatile ammonium buffers
      traditionally used in native mass spectrometry.

PMID- 28510996
TI  - Tramadol with or without paracetamol (acetaminophen) for cancer pain.
AB  - BACKGROUND: Tramadol is an opioid analgesic licensed for use in moderate to
      severe pain. It is considered as a low risk for abuse, so control regulations are
      not as stringent as for 'strong' opioids such as morphine. It has a potential
      role as a step 2 option of the World Health Organization (WHO) analgesic ladder.
      OBJECTIVES: To assess the benefits and adverse effects of tramadol with or
      without paracetamol (acetaminophen) for cancer-related pain. SEARCH METHODS: We
      searched the following databases using a wide range of search terms: the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We
      also searched three clinical trials registry databases. The date of the last
      search was 2 November 2016. SELECTION CRITERIA: We selected studies that were
      randomised, with placebo or active controls, or both, and included a minimum of
      10 participants per treatment arm. We were interested particularly in blinded
      studies, but also included open studies.We excluded non-randomised studies,
      studies of experimental pain, case reports, and clinical observations. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data using a
      standard form and checked for agreement before entry into Review Manager 5. We
      included information about the number of participants treated and demographic
      details, type of cancer, drug and dosing regimen, study design (placebo or active
      control) and methods, study duration and follow-up, analgesic outcome measures
      and results, withdrawals, and adverse events. We collated multiple reports of the
      same study, so that each study, rather than each report, was the unit of interest
      in the review. We assessed the evidence using GRADE and created a 'Summary of
      findings' table.The main outcomes of interest for benefit were pain reduction of
      30% or greater and 50% or greater from baseline, participants with pain no worse
      than mild, and participants feeling much improved or very much improved. MAIN
      RESULTS: We included 10 studies (12 reports) with 958 adult participants. All the
      studies enrolled participants with chronic malignant tumour-related pain who were
      experiencing pain intensities described as moderate to severe, with most
      experiencing at least 4/10 with current treatment. The mean ages were 59 to 70
      years, with participants aged between 24 and 87 years. Study length ranged from
      one day to six months. Five studies used a cross-over design. Tramadol doses
      ranged from 50 mg as single dose to 600 mg per day; doses of 300 mg per day to
      400 mg per day were most common.Nine studies were at high risk of bias for one to
      four criteria (only one high risk of bias for size). We judged all the results to
      be very low quality evidence because of widespread lack of blinding of outcome
      assessment, inadequately described sequence generation, allocation concealment,
      and small numbers of participants and events. Important outcomes were poorly
      reported. There were eight different active comparators and one comparison with
      placebo. There was little information available for any comparison and no firm
      conclusions could be drawn for any outcome.Single comparisons of oral tramadol
      with codeine plus paracetamol, of dihydrocodeine, and of rectal versus oral
      tramadol provided no data for key outcomes. One study used tramadol combined with
      paracetamol; four participants received this intervention. One study compared
      tramadol with flupirtine - a drug that is no longer available. One study compared
      tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen,
      but the dosing schedule poorly explained.Two studies (191 participants) compared
      tramadol with buprenorphine. One study (131 participants) reported a similar
      proportion of no or mild pain at 14 days.Three studies (300 participants)
      compared tramadol with morphine. Only one study, combining tramadol, tramadol
      plus paracetamol, and paracetamol plus codeine as a single weak-opioid group
      reported results. Weak opioid produced reduction in pain of at least 30% from
      baseline in 55/117 (47%) participants, compared with 91/110 (82%) participants
      with morphine. Weak opioid produced reduction in pain of at least 50% in 49/117
      (42%) participants, compared with 83/110 (75%) participants with morphine.There
      was no useful information for any other outcome of benefit or harm. AUTHORS'
      CONCLUSIONS: There is limited, very low quality, evidence from randomised
      controlled trials that tramadol produced pain relief in some adults with pain due
      to cancer and no evidence at all for children. There is very low quality evidence
      that it is not as effective as morphine. This review does not provide a reliable
      indication of the likely effect. The likelihood that the effect will be
      substantially different is very high. The place of tramadol in managing cancer
      pain and its role as step 2 of the WHO analgesic ladder is unclear.

PMID- 28510997
TI  - Impact of m-health application used by community health volunteers on improving
      utilisation of maternal, new-born and child health care services in a rural area
      of Uttar Pradesh, India.
AB  - OBJECTIVE: To raise the quality of counselling by community health volunteers
      resulting in improved uptake of maternal, neonatal and child health services
      (MNCH), an m-health application was introduced under a project named 'Reducing
      Maternal and Newborn Deaths (ReMiND)' in district Kaushambi in India. We report
      the impact of this project on coverage of key MNCH services. METHODS: A pre- and
      post-quasi-experimental design was undertaken to assess the impact of
      intervention. This project was introduced in two community development blocks in
      Kaushambi district in 2012. Two other blocks from the same district were selected
      as controls after matching for coverage of two indicators at baseline - antenatal
      care and institutional deliveries. The Annual Health Survey conducted by the
      Ministry of Health and Family Welfare in 2011 served as pre-intervention data,
      whereas a household survey in four blocks of Kaushambi district in 2015 provided
      post-intervention coverage of key services. Propensity score matched samples from
      intervention and control areas in pre-intervention and post-intervention periods
      were analysed using difference-in-difference method to estimate the impact of
      ReMiND project. RESULTS: We found a statistically significant increase in
      coverage of iron-folic acid supplementation (12.58%), self-reporting of
      complication during pregnancy (13.11%) and after delivery (19.6%) in the
      intervention area. The coverage of three or more antenatal care visits, tetanus
      toxoid vaccination, full antenatal care and ambulance usage increased in
      intervention area by 10.3%, 4.28%, 1.1% and 2.06%, respectively; however, the
      changes were statistically insignificant. CONCLUSION: Three of eight services
      which were targeted for improvement under ReMiND project registered a significant
      improvement as result of m-health intervention.

PMID- 28510999
TI  - NGWA News.

PMID- 28510998
TI  - New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands
      Clinic, Harare, Zimbabwe: retrospective cohort analysis.
AB  - OBJECTIVE: To assess the incidence and associated factors of Type 2 Diabetes
      Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. METHODS: We
      analysed data of all HIV-infected patients older than 16 years who attended
      Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers
      patients whose random blood sugar is higher than 11.1 mmol/l and which is
      confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is
      also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors
      for developing T2DM were identified using Cox proportional hazard models adjusted
      for confounding. Missing baseline BMI data were multiply imputed. Results are
      presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI).
      RESULTS: Data for 4,110 participants were included: 67.2% were women; median age
      was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337)
      cells/mm3 . The proportion of participants with hypertension at baseline was
      15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57
      patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per
      1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR:
      1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m2 )
      (aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and
      male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the
      risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO
      clinical stage) were not independent risk factors for developing T2DM.
      CONCLUSION: Although the incidence of T2DM in this HIV cohort was lower than that
      has been observed in others, our results show that risk factors for developing
      T2DM among HIV-infected people are similar to those of the general population.
      HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care
      that includes better health services for prevention, early detection and
      treatment of chronic diseases especially among the elderly and obese.

PMID- 28511000
TI  - Superconducting Ferromagnetic Nanodiamond.
AB  - Superconductivity and ferromagnetism are two mutually antagonistic states in
      condensed matter. Research on the interplay between these two competing orderings
      sheds light not only on the cause of various quantum phenomena in strongly
      correlated systems but also on the general mechanism of superconductivity. Here
      we report on the observation of the electronic entanglement between
      superconducting and ferromagnetic states in hydrogenated boron-doped nanodiamond
      films, which have a superconducting transition temperature Tc ~ 3 K and a Curie
      temperature TCurie > 400 K. In spite of the high TCurie, our nanodiamond films
      demonstrate a decrease in the temperature dependence of magnetization below 100
      K, in correspondence to an increase in the temperature dependence of resistivity.
      These anomalous magnetic and electrical transport properties reveal the presence
      of an intriguing precursor phase, in which spin fluctuations intervene as a
      result of the interplay between the two antagonistic states. Furthermore, the
      observations of high-temperature ferromagnetism, giant positive
      magnetoresistance, and anomalous Hall effect bring attention to the potential
      applications of our superconducting ferromagnetic nanodiamond films in
      magnetoelectronics, spintronics, and magnetic field sensing.

PMID- 28511001
TI  - Monolayer Solid-State Electrolyte for Electric Double Layer Gating of Graphene
      Field-Effect Transistors.
AB  - The electrostatic gating of graphene field-effect transistors is demonstrated
      using a monolayer electrolyte. The electrolyte, cobalt crown ether phthalocyanine
      (CoCrPc) and LiClO4, is deposited as a monolayer on the graphene channel,
      essentially creating an additional two-dimensional layer on top of graphene. The
      crown ethers on the CoCrPc solvate lithium ions and the ion location is modulated
      by a backgate without requiring liquid solvent. Ions dope the channel by inducing
      image charges; the doping level (i.e., induced charge density) can be modulated
      by the backgate bias with the extent of the surface potential change being
      controlled by the magnitude and polarity of the backgate bias. With a crown ether
      to Li+ ratio of 5:1, programming tests for which the backgate is held at -VBG
      shift the Dirac point by ~15 V, corresponding to a sheet carrier density on the
      order of 1012 cm-2. This charge carrier density agrees with the packing density
      of monolayer CoCrPc on graphene that would be expected with one Li+ for every
      five crown ethers (at the maximum possible Li+ concentration, 1013 cm-2 is
      predicted). The crown ethers provide two stable states for the Li+: one near the
      graphene channel (low-resistance state) and one ~5 A away from the channel (high
      resistance state). Initial state retention measurements indicate that the two
      states can be maintained for at least 30 min (maximum time monitored), which is
      106 times longer than polymer-based electrolytes at room temperature, with at
      least a 250 Omega MUm difference between the channel resistance in the high- and
      low-resistance states.

PMID- 28511002
TI  - Exploring High-Performance n-Type Thermoelectric Composites Using Amino
      Substituted Rylene Dimides and Carbon Nanotubes.
AB  - Taking advantage of the high electrical conductivity of a single-walled carbon
      nanotube (SWCNT) and the large Seebeck coefficient of rylene diimide, a
      convenient strategy is proposed to achieve high-performance n-type thermoelectric
      (TE) composites containing a SWCNT and amino-substituted perylene diimide (PDINE)
      or naphthalene diimide (NDINE). The obtained n-type composites display greatly
      enhanced TE performance with maximum power factors of 112 +/- 8 (PDINE/SWCNT) and
      135 +/- 14 (NDINE/SWCNT) MUW m-1 K-2. A short doping time of 0.5 h can ensure
      high TE performance. The corresponding TE module consisting of five p-n junctions
      reaches a large output power of 3.3 MUW under a 50  degrees C temperature
      gradient. In addition, the n-type composites exhibit high air stability and
      excellent thermal stability. This design strategy benefits the future fabricating
      of high-performance n-type TE materials and devices.

PMID- 28511003
TI  - Functionalized Graphene Enables Highly Efficient Solar Thermal Steam Generation.
AB  - The ability to efficiently utilize solar thermal energy to enable liquid-to-vapor
      phase transition has great technological implications for a wide variety of
      applications, such as water treatment and chemical fractionation. Here, we
      demonstrate that functionalizing graphene using hydrophilic groups can greatly
      enhance the solar thermal steam generation efficiency. Our results show that
      specially functionalized graphene can improve the overall solar-to-vapor
      efficiency from 38% to 48% at one sun conditions compared to chemically reduced
      graphene oxide. Our experiments show that such an improvement is a surface effect
      mainly attributed to the more hydrophilic feature of functionalized graphene,
      which influences the water meniscus profile at the vapor-liquid interface due to
      capillary effect. This will lead to thinner water films close to the three-phase
      contact line, where the water surface temperature is higher since the resistance
      of thinner water film is smaller, leading to more efficient evaporation. This
      strategy of functionalizing graphene to make it more hydrophilic can be
      potentially integrated with the existing macroscopic heat isolation strategies to
      further improve the overall solar-to-vapor conversion efficiency.

PMID- 28511004
TI  - Lithium Batteries with Nearly Maximum Metal Storage.
AB  - The drive for significant advancement in battery capacity and energy density
      inspired a revisit to the use of Li metal anodes. We report the use of a seamless
      graphene-carbon nanotube (GCNT) electrode to reversibly store Li metal with
      complete dendrite formation suppression. The GCNT-Li capacity of 3351 mAh g-1GCNT
      Li approaches that of bare Li metal (3861 mAh g-1Li), indicating the low
      contributing mass of GCNT, while yielding a practical areal capacity up to 4 mAh
      cm-2 and cycle stability. A full battery based on GCNT-Li/sulfurized carbon (SC)
      is demonstrated with high energy density (752 Wh kg-1 total electrodes, where
      total electrodes = GCNT-Li + SC + binder), high areal capacity (2 mAh cm-2), and
      cyclability (80% retention at >500 cycles) and is free of Li polysulfides and
      dendrites that would cause severe capacity fade.

PMID- 28511005
TI  - Characterization of l-Theanine Excitatory Actions on Hippocampal Neurons: Toward
      the Generation of Novel N-Methyl-d-aspartate Receptor Modulators Based on Its
      Backbone.
AB  - l-Theanine (or l-gamma-N-ethyl-glutamine) is the major amino acid found in
      Camellia sinensis. It has received much attention because of its pleiotropic
      physiological and pharmacological activities leading to health benefits in
      humans, especially. We describe here a new, easy, efficient, and environmentally
      friendly chemical synthesis of l-theanine and l-gamma-N-propyl-Gln and their
      corresponding d-isomers. l-Theanine, and its derivatives obtained so far,
      exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors,
      with no detectable agonist effect at other glutamate receptors, on cultured
      hippocampal neurons. This activity was retained on NMDA receptors expressed in
      Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors
      were equally modulated by l-theanine. The stereochemical change from l-theanine
      to d-theanine along with the substitution of the ethyl for a propyl moiety in the
      gamma-N position of l- and d-theanine significantly enhanced the biological
      efficacy, as measured on cultured hippocampal neurons. l-Theanine structure thus
      represents an interesting backbone to develop novel NMDA receptor modulators.

PMID- 28511007
TI  - Thicker Lamellae and Higher Crystallinity of Poly(lactic acid) via Applying Shear
      Flow and Pressure and Adding Poly(ethylene Glycol).
AB  - In this work, we explored the crystallization of poly(lactic acid) (PLA) blended
      with poly(ethylene glycol) (PEG) under two inevitable processing fields (i.e.,
      flow and pressure) that coexist in almost all processing for the first time.
      Here, the PEG was incorporated into PLA as a molecular chain activity promoter to
      induce PLA crystallization. A homemade pressuring and shearing device was
      utilized to prepare samples and necessary characterization methods, such as
      differential scanning calorimetry, scanning electron microscopy, and synchrotron
      radiation, and were used to investigated the joint effects of PEG, pressure, and
      shear flow on the crystallization behaviors and morphologies of PLA/PEG samples.
      The results reveal that adding 3-5 wt % PEG into PLA can significantly increase
      the PLA crystallinity due to the efficient plasticization effect of PEG, while
      the PEG content reaches 10 wt %, the PLA crystallinity decreases drastically as
      the phase separation between PEG and PLA occurs. We also find that applying a
      higher pressure (~100 MPa) can facilitate the formation of thicker lamellae with
      fewer defects as well as higher crystallinity under an equal degree of
      supercooling compared to normal pressure or a low pressure condition because the
      slip of molecular chains during crystallization makes the lamellae thicker under
      higher pressures. The PLA crystalline structure in the PLA/PEG sample is not
      influenced by the shear flow, yet the crystallinity is largely enhanced by
      applying a shear flow with an appropriate intensity (0-3.5 s-1). It is worth
      noting that pressure and shear flow show a synergetic effect to fabricate PLA/PEG
      samples with high crystallinity. These meaningful results could beyond doubt help
      comprehend the relationship between crystallization conditions and
      crystallization behaviors of PLA/PEG samples and thus provide guidance to obtain
      high-performance PLA/PEG products via controlling crystallization conditions.

PMID- 28511006
TI  - Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores
      Dopaminergic Neuron Function in a Rat Parkinson's Disease Model.
AB  - Therapies capable of decelerating, or perhaps even halting, neurodegeneration in
      Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy
      testing the delivery of neurotrophic factors, such as the glial cell-line derived
      neurotrophic factor (GDNF), have been largely ineffective due to poor vector
      distribution throughout the diseased regions in the brain. In addition, current
      delivery strategies involve invasive procedures that obviate the inclusion of
      early stage patients who are most likely to benefit from GDNF-based gene therapy.
      Here, we introduce a two-pronged treatment strategy, composed of MR image-guided
      focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN), that provides
      widespread but targeted GDNF transgene expression in the brain following systemic
      administration. MR image-guided FUS allows circulating gene vectors to partition
      into the brain tissue by noninvasive and transient opening of the blood-brain
      barrier (BBB) within the areas where FUS is applied. Once beyond the BBB, BPN
      provide widespread and uniform GDNF expression throughout the targeted brain
      tissue. After only a single treatment, our strategy led to therapeutically
      relevant levels of GDNF protein content in the FUS-targeted regions in the
      striatum of the 6-OHDA-induced rat model of PD, which lasted at least up to 10
      weeks. Importantly, our strategy restored both dopamine levels and dopaminergic
      neuron density and reversed behavioral indicators of PD-associated motor
      dysfunction with no evidence of local or systemic toxicity. Our combinatorial
      approach overcomes limitations of current delivery strategies, thereby
      potentially providing a novel means to treat PD.

PMID- 28511008
TI  - Cascade Reaction-Based, Near-Infrared Multiphoton Fluorescent Probe for the
      Selective Detection of Cysteine.
AB  - The ability to detect and visualize cellular events and their associated target
      biological analytes through use of cell-permeable profluorogenic probes is
      dependent on the availability of activatable probes that respond rapidly and
      selectively to target analytes by production of fluorescent reporting molecules
      whose excitation and emission energies span a broad range. Herein is described a
      new probe, DCM-Cys, that preferentially reacts with cysteine to form a
      dicyanomethylene-4H-pyran (DCM) reporter whose red-energy fluorescence can be
      stimulated by two-photon, near-infrared excitation so as to provide visualization
      of cysteine presence inside living human cells with a high signal-to-background
      ratio. These aforementioned characteristics and the ability of DCM-Cys to provide
      selective, nanomolar-level in vitro cysteine detection, as demonstrated by its
      lack of significant response to other thiols and potential interfering agents
      from biological environments, are attributed to the molecular designs of the DCM
      Cys probe and DCM reporter. Attachment of an acryl moiety to the DCM reporter via
      a self-eliminating, electron-withdrawing benzyl alcohol-carbamate linker offers a
      probe having selective, sensitive reaction with cysteine to rapidly produce a
      reporter whose energies of excitation and emission (lambdaabsreport = 480 nm,
      lambdaemisreport = 640 nm) are red-shifted from those of the DCM-Cys probe
      (lambdaabsprobe = 440 nm, lambdaemisprobe = 550 nm), thereby leading to low
      background signal from abundant probe and a large signal from the resulting
      reporter of cysteine presence.

PMID- 28511010
TI  - pi-Extended and Curved Antiaromatic Polycyclic Hydrocarbons.
AB  - Synthesis of antiaromatic polycyclic hydrocarbons (PHs) is challenging because
      the high energy of their highest occupied molecular orbital and low energy of
      their lowest unoccupied molecular orbital cause them to be reactive and unstable.
      In this work, two large antiaromatic acene analogues, namely,
      cyclopenta[pqr]indeno[2,1,7-ijk]tetraphene (CIT, 1a) and
      cyclopenta[pqr]indeno[7,1,2-cde]picene (CIP, 1b), as well as a curved
      antiaromatic molecule with 48 pi-electrons, dibenzo[a,c]diindeno[7,1,2
      fgh:7',1',2'-mno]phenanthro[9,10-k]tetraphene (DPT, 1c), are synthesized on the
      basis of the corona of indeno[1,2-b]fluorene. These three antiaromatic PHs
      possess a narrow energy gap down to 1.55 eV and exhibit high kinetic stability
      under ambient conditions. Moreover, these compounds display reversible electron
      transfer processes in both the cathodic and anodic regimes. Their cation and
      anion radicals are characterized by in situ vis-NIR absorption and electron
      paramagnetic resonance spectroelectrochemistry. The X-ray crystallographic
      analysis confirms that while CIP and CIT manifest planar structures, DPT shows a
      curved pi-conjugated carbon skeleton. The synthetic strategy starting from ortho
      substituted benzene units to construct five-membered rings in this work provides
      a unique entry to novel pentagon-embedding or curved antiaromatic polycyclic
      hydrocarbons. In addition, besides the detailed chemical and physical
      investigations, microscale single-crystal fiber field-effect transistors were
      also fabricated.

PMID- 28511009
TI  - The Development of Target-Specific Pose Filter Ensembles To Boost Ligand
      Enrichment for Structure-Based Virtual Screening.
AB  - Structure-based virtual screening (SBVS) has become an indispensable technique
      for hit identification at the early stage of drug discovery. However, the
      accuracy of current scoring functions is not high enough to confer success to
      every target and thus remains to be improved. Previously, we had developed binary
      pose filters (PFs) using knowledge derived from the protein-ligand interface of a
      single X-ray structure of a specific target. This novel approach had been
      validated as an effective way to improve ligand enrichment. Continuing from it,
      in the present work we attempted to incorporate knowledge collected from diverse
      protein-ligand interfaces of multiple crystal structures of the same target to
      build PF ensembles (PFEs). Toward this end, we first constructed a comprehensive
      data set to meet the requirements of ensemble modeling and validation. This set
      contains 10 diverse targets, 118 well-prepared X-ray structures of protein-ligand
      complexes, and large benchmarking actives/decoys sets. Notably, we designed a
      unique workflow of two-layer classifiers based on the concept of ensemble
      learning and applied it to the construction of PFEs for all of the targets.
      Through extensive benchmarking studies, we demonstrated that (1) coupling PFE
      with Chemgauss4 significantly improves the early enrichment of Chemgauss4 itself
      and (2) PFEs show greater consistency in boosting early enrichment and larger
      overall enrichment than our prior PFs. In addition, we analyzed the pairwise
      topological similarities among cognate ligands used to construct PFEs and found
      that it is the higher chemical diversity of the cognate ligands that leads to the
      improved performance of PFEs. Taken together, the results so far prove that the
      incorporation of knowledge from diverse protein-ligand interfaces by ensemble
      modeling is able to enhance the screening competence of SBVS scoring functions.

PMID- 28511011
TI  - Iron Hydroperoxide Intermediate in Superoxide Reductase: Protonation or
      Dissociation First? MM Dynamics and QM/MM Metadynamics Study.
AB  - Superoxide reductase is a mononuclear iron enzyme involved in superoxide radical
      detoxification in some bacteria. Its catalytic mechanism is associated with the
      remarkable formation of a ferric hydroperoxide Fe3+-OOH intermediate, which is
      specifically protonated on its proximal oxygen to generate the reaction product
      H2O2. Here, we present a computational study of the protonation mechanism of the
      Fe3+-OOH intermediate, at different levels of theory. This was performed on the
      whole system (solvated protein) using well-tempered metadynamics at the QM/MM
      (B3LYP/AmberFF99SB) level. Enabled by the development of a new set of force field
      parameters for the active site, a conformational MM study of the Fe3+-OOH species
      gave insights into its solvation pattern, in addition to generating the two
      starting conformations for the ab initio metadynamics setup. Two different
      protonation mechanisms for the Fe3+-OOH intermediate have been found depending on
      the starting structure. Whereas a possible mechanism involves at first the
      protonation of the hydroperoxide ligand and then dissociation of H2O2, the most
      probable one starts with an unexpected dissociation of the HOO- ligand from the
      iron, followed by its protonation. This favored reactivity was specifically
      linked to the influence of both the nearby conserved lysine 48 residue and the
      microsolvatation on the charge distribution of the oxygens of the HOO- ligand.
      These data highlight the crucial role of the whole environment, solvent, and
      protein, to describe accurately this second protonation step in superoxide
      reductase. This is clearly not possible with smaller models unable to reproduce
      correctly the mechanistically determinant charge distribution.

PMID- 28511012
TI  - Nonlinear Optical Magnetism Revealed by Second-Harmonic Generation in
      Nanoantennas.
AB  - Nonlinear effects at the nanoscale are usually associated with the enhancement of
      electric fields in plasmonic structures. Recently emerged new platform for
      nanophotonics based on high-index dielectric nanoparticles utilizes optically
      induced magnetic response via multipolar Mie resonances and provides novel
      opportunities for nanoscale nonlinear optics. Here, we observe strong second
      harmonic generation from AlGaAs nanoantennas driven by both electric and magnetic
      resonances. We distinguish experimentally the contribution of electric and
      magnetic nonlinear response by analyzing the structure of polarization states of
      vector beams in the second-harmonic radiation. We control continuously the
      transition between electric and magnetic nonlinearities by tuning polarization of
      the optical pump. Our results provide a direct observation of nonlinear optical
      magnetism through selective excitation of multipolar nonlinear modes in
      nanoantennas.

PMID- 28511013
TI  - Reversible, Tunable, Electric-Field Driven Assembly of Silver Nanocrystal
      Superlattices.
AB  - Nanocrystal superlattices are typically fabricated by either solvent evaporation
      or destabilization methods that require long time periods to generate highly
      ordered structures. In this paper, we report for the first time the use of
      electric fields to reversibly drive nanocrystal assembly into superlattices
      without changing solvent volume or composition, and show that this method only
      takes 20 min to produce polyhedral colloidal crystals, which would otherwise need
      days or weeks. This method offers a way to control the lattice constants and
      degree of preferential orientation for superlattices and can suppress the
      uniaxial superlattice contraction associated with solvent evaporation. In situ
      small-angle X-ray scattering experiments indicated that nanocrystal superlattices
      were formed while solvated, not during drying.

PMID- 28511015
TI  - Multistereocenter-Containing Cyclopentanoids from Ynamides via Oxazolidinone
      Controlled Nazarov Cyclization.
AB  - Achieving ready-enantioselective access to multistereocenter-containing
      cyclopentyl rings is an area of great significance to organic synthesis. In this
      work, we describe a general protocol for accessing multistereocenter-containing
      cyclopentanoids from simple N-alkynyloxazolidinones (Ox-ynamides). This protocol
      involves conversion of Ox-ynamides into Ox-activated divinyl and aryl vinyl
      ketones that undergo facile Nazarov cyclization with excellent chemo-, regio-,
      and stereocontrol. The Ox auxiliary directs all aspects of reactivity and
      selectivity, both in the electrocyclization and in the subsequent transformations
      of the resulting oxyallyl intermediate. Stereoinduction in the electrocyclization
      results from a "coupled-torque" mechanism in which rotation of the Ox group,
      driven by increasing orbital overlap of the nitrogen lone pair with the incipient
      oxyallyl cation, is coupled with the rotation of the termini of the pentadienyl
      cation, favoring a particular direction of conrotatory ring closure
      (torquoselectivity). The associated lone-pair stabilization of the transition
      state by Ox promotes cyclization of traditionally resistant substrates,
      broadening the scope of this asymmetric Nazarov cyclization. The Ox group also
      facilitates the stereo- and regioselective incorporation of nucleophiles (Nu) and
      dienes, giving more complex, multistereocenter containing cyclopentanoids.
      Finally, the Ox group is readily removed and recovered or can be converted into
      other amine functionalities.

PMID- 28511014
TI  - Protein Corona Formation on Colloidal Polymeric Nanoparticles and Polymeric
      Nanogels: Impact on Cellular Uptake, Toxicity, Immunogenicity, and Drug Release
      Properties.
AB  - The adsorption of biomolecules to the surface of nanoparticles (NPs) following
      administration into biological environments is widely recognized. In particular,
      the "protein corona" is well understood in terms of formation kinetics and impact
      upon the biological interactions of NPs. Its presence is an essential
      consideration in the design of therapeutic NPs. In the present study, the protein
      coronas of six polymeric nanoparticles of prospective therapeutic use were
      investigated. These included three colloidal NPs-soft core-multishell (CMS) NPs,
      plus solid cationic Eudragit RS (EGRS), and anionic ethyl cellulose (EC)
      nanoparticles-and three nanogels (NGs)-thermoresponsive dendritic-polyglycerol
      (dPG) nanogels (NGs) and two amino-functionalized dPG-NGs. Following incubation
      with human plasma, protein coronas were characterized and their biological
      interactions compared with pristine NPs. All NPs demonstrated protein adsorption
      and increased hydrodynamic diameters, although the solid EGRS and EC NPs bound
      notably more protein than the other tested particles. Shifts toward moderately
      negative surface charges were also observed for all corona bearing NPs, despite
      varied zeta potentials in their pristine states. While the uptake and cellular
      adhesion of the colloidal NPs in primary human keratinocytes and human umbilical
      vein endothelial cells were significantly decreased when bearing the protein
      corona, no obvious impact was seen in the NGs. By contrast, corona bearing NGs
      induced marked increases in cytokine release from primary human macrophages not
      seen with corona bearing colloidal NPs. Despite this, no apparent enhancement to
      in vitro toxicity was noted. Finally, drug release from EGRS and EC NPs was
      assessed, where a decrease was seen in the EGRS NPs alone. Together these results
      provide a direct comparison of the physical and biological impact the protein
      corona has on NPs of widely varied character and in particular highlights a
      distinction between the corona's effects on NGs and colloidal NPs.

PMID- 28511017
TI  - Thermal Evolution of One-Dimensional Iodine Chains.
AB  - In one-dimensional (1D) systems, the definition of three common states of matter
      (solid, liquid, and gas) becomes obscure because it has been theoretically
      predicted that a 1D system has no phase transition. Due to technical difficulty
      in tracking 1D thermal evolution, hardly any experimental evidence has
      demonstrated whether there exist these three states. Here we report Raman
      experimental observation that 1D iodine molecular chains formed inside the
      nanosized channel undergo continuous transformation from chain structure to
      single molecules with increasing temperature, without having a sudden change as
      commonly observed in phase transition. At low temperatures, short-range order
      exists and manifests itself as long chains in structure, which gradually break
      into shorter chains with increasing temperature. The 1D system progressively gets
      more and more disordered, which is in agreement with the theoretical derivations.
      Our work may benefit the emerging molecular scale electronics.

PMID- 28511016
TI  - Structural and Biochemical Insights into Dimethylsulfoniopropionate Cleavage by
      Cofactor-Bound DddK from the Prolific Marine Bacterium Pelagibacter.
AB  - Enormous amounts of the organic osmolyte dimethylsulfoniopropionate (DMSP) are
      produced in marine environments where bacterial DMSP lyases cleave it, yielding
      acrylate and the climate-active gas dimethyl sulfide (DMS). SAR11 bacteria are
      the most abundant clade of heterotrophic bacteria in the oceans and play a key
      role in DMSP catabolism. An important environmental factor affecting DMS
      generation via DMSP lyases is the availability of metal ions because they are
      essential cofactors for many of these enzymes. Here we examine the structure and
      activity of DddK in the presence of various metal ions. We have established that
      DddK containing a double-stranded beta-helical motif utilizes various divalent
      metal ions as cofactors for catalytic activity. However, nickel, an abundant
      metal ion in marine environments, adopts a distorted octahedral coordination
      environment and conferred the highest DMSP lyase activity. Crystal structures of
      cofactor-bound DddK reveal key metal ion binding and catalytic residues and
      provide the first rationalization for varying activities with different metal
      ions. The structures of DddK along with site-directed mutagenesis and ultraviolet
      visible studies are consistent with Tyr 64 acting as a base to initiate the beta
      elimination reaction of DMSP. Our biochemical and structural studies provide a
      detailed understanding of DMS generation by one of the ocean's most prolific
      bacteria.

PMID- 28511018
TI  - Daytime increase in caloric intake without change in total 24-h caloric intake
      can increase adiposity but not total bodyweight in rats with inverted feeding
      pattern.
AB  - The goal of this study was to evaluate the effect of the food availability period
      on body weight, self-selection of macronutrients, adiposity, lipoprotein, and
      serum glucose profiles without changing energy intake. Young male rats were
      divided into 2 groups according to the availability of food during the light and
      dark phases of the cycle, forming 2 groups: control group (CG) and group with
      inverted feeding pattern (IFPG). Before inversion of food availability on the
      80th day, circadian food intake was measured every 4 h over 24 h during 3 days.
      The glycemic curve, an oral test for glucose tolerance, and self-selection of
      macronutrients were evaluated. Blood samples were collected for analysis of
      fasting glucose, triglycerides, and total cholesterol fractions. The IFPG showed
      an increase in fasting glucose in the dark phase of the cycle, changes in the
      glycemic curve, and oral glucose tolerance test. It also showed increased
      abdominal and liver fat and distinct choice of macronutrients compared with the
      CG. A change in the availability of food according to the phase of the circadian
      cycle produces changes in glucose and feeding circadian rhythm culminating in
      increased abdominal and hepatic fat. These effects can increase the risk of
      metabolic disorders and installation of chronic diseases.

PMID- 28511019
TI  - A novel GRK1 mutation in an Italian patient with Oguchi disease.

PMID- 28511020
TI  - Acute high-intensity interval running increases markers of gastrointestinal
      damage and permeability but not gastrointestinal symptoms.
AB  - The purpose of this study was to investigate the effects of high-intensity
      interval running on markers of gastrointestinal (GI) damage and permeability
      alongside subjective symptoms of GI discomfort. Eleven male runners completed an
      acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at
      120% maximal oxygen uptake) where markers of GI permeability, intestinal damage,
      and GI discomfort symptoms were assessed and compared with resting conditions.
      Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio
      (0.051 +/- 0.016 vs. 0.031 +/- 0.021, p = 0.0047; 95% confidence interval (CI) =
      0.006 to 0.036) and sucrose concentrations (0.388 +/- 0.217 vs. 0.137 +/- 0.148
      mg.L-1; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary
      lactulose/rhamnose (0.032 +/- 0.005 vs. 0.030 +/- 0.005; p = 0.3; 95% CI = -0.012
      to 0.009) or sucrose concentrations (0.169% +/- 0.168% vs. 0.123% +/- 0.120%; p =
      0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting
      conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was
      significantly increased (p < 0.001) during and in the recovery period from HIIT
      whereas no changes were observed during rest. Mild symptoms of GI discomfort were
      reported immediately and at 24 h post-HIIT, although these symptoms did not
      correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI
      permeability and intestinal I-FABP release, although these do not correlate with
      symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data
      showing that it is possible to detect changes in intestinal permeability that is
      not observed using urinary sampling over a shorter time-period.

PMID- 28511021
TI  - The Selectivity Challenge in Organic Solvent Nanofiltration: Membrane and Process
      Solutions.
AB  - Recent development of organic solvent nanofiltration (OSN) materials has been
      overwhelmingly directed toward tight membranes with ultrahigh permeance. However,
      emerging research into OSN applications is suggesting that improved separation
      selectivity is at least as important as further increases in membrane permeance.
      Membrane solutions are being proposed to improve selectivity, mostly by
      exploiting solute/solvent/membrane interactions and by fabricating tailored
      membranes. Because achieving a perfect separation with a single membrane stage is
      difficult, process engineering solutions, such as membrane cascades, are also
      being advocated. Here we review these approaches to the selectivity challenge,
      and to clarify our analysis, we propose a selectivity figure of merit that is
      based on the permselectivity between the two solutes undergoing separation as
      well as the ratio of their molecular weights.

PMID- 28511022
TI  - Neurologie an der Universitat Leipzig. Beitrage zur Entwicklung des klinischen
      Fachgebietes von 1880 bis 1985, by Armin Wagner and Holger Steinberg.

PMID- 28511023
TI  - Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH: a
      randomized controlled clinical trial.
AB  - Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty
      liver disease, is one of the most common hepatic diseases in children. We
      conducted a randomized controlled clinical trial on children with biopsy-proven
      NASH based on a combinatorial nutritional approach compared with placebo.
      Participants were assigned to lifestyle modification plus placebo or lifestyle
      modification plus a mix containing docosahexaenoic acid, choline, and vitamin E
      (DHA-CHO-VE). Forty children and adolescents participated in the entire trial.
      The primary outcome was the improvement of liver hyperechogenicity. Secondary
      outcomes included alterations of alanine aminotransferase (ALT) and other
      metabolic parameters. Furthermore, changes of serum bile acids (BA) and plasma
      fibroblast growth factor 19 (FGF19) levels were evaluated as inverse biomarkers
      of disease severity. At the end of the study, we observed a significant decrease
      in severe steatosis in the treatment group (50% to 5%, p = 0.001). Furthermore,
      although the anthropometric and biochemical measurements in the placebo and DHA
      CHO-VE groups were comparable at baseline, at the end of the study ALT and
      fasting glucose levels improved only in the treatment group. Finally, we found
      that BA levels were not influenced whereas FGF19 levels were significantly
      increased by DHA-CHO-VE. The results suggest that a combination of DHA, VE, and
      CHO could improve steatosis and reduce ALT and glucose levels in children with
      NASH. However, further studies are needed to assess the impact of a DHA and VE
      combination on repair of liver damage in paediatric NASH.

PMID- 28511024
TI  - Cardiopulmonary Exercise Testing and Surgery.
AB  - The surgical patient population is increasingly elderly and comorbid and poses
      challenges to perioperative physicians. Accurate preoperative risk stratification
      is important to direct perioperative care. Reduced aerobic fitness is associated
      with increased postoperative morbidity and mortality. Cardiopulmonary exercise
      testing is an integrated and dynamic test that gives an objective measure of
      aerobic fitness or functional capacity and identifies the cause of exercise
      intolerance. Cardiopulmonary exercise testing provides an individualized estimate
      of patient risk that can be used to predict postoperative morbidity and
      mortality. This technology can therefore be used to inform collaborative decision
      making and patient consent, to triage the patient to an appropriate perioperative
      care environment, to diagnose unexpected comorbidity, to optimize medical
      comorbidities preoperatively, and to direct individualized preoperative exercise
      programs. Functional capacity, evaluated as the anaerobic threshold and peak
      oxygen uptake ([Formula: see text]o2peak) predicts postoperative morbidity and
      mortality in the majority of surgical cohort studies. The ventilatory equivalents
      for carbon dioxide (an index of gas exchange efficiency), is predictive of
      surgical outcome in some cohorts. Prospective cohort studies are needed to
      improve the precision of risk estimates for different patient groups and to
      clarify the best combination of variables to predict outcome. Early data suggest
      that preoperative exercise training improves fitness, reduces the debilitating
      effects of neoadjuvant chemotherapy, and may improve clinical outcomes. Further
      research is required to identify the most effective type of training and the
      minimum duration required for a positive effect.

PMID- 28511028
TI  - Corrigendum.

PMID- 28511026
TI  - HDAC2 is required by the physiological concentration of glucocorticoid to inhibit
      inflammation in cardiac fibroblasts.
AB  - We previously suggested that endogenous glucocorticoids (GCs) may inhibit
      myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the
      possible cellular and molecular mechanisms were poorly understood. In this study,
      we investigated the role of physiological concentration of GCs in inflammation
      induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The
      results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to
      endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of
      TNF-alpha and IL-1beta in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X)
      system impaired the anti-inflammatory action of GCs through downregulating HDAC2
      activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory
      effects of physiological level of hydrocortisone, and blunted the ability of XO/X
      system to downregulate the inhibitory action of physiological level of
      hydrocortisone on cytokines. These results suggested that HDAC2 was required by
      the physiological concentration of GC to inhibit inflammatory response. The
      dysfunction of HDAC2 induced by oxidative stress might be account for GC
      resistance and chronic inflammatory disorders during the cardiac diseases.

PMID- 28511025
TI  - Co-inheritance of the membrane frizzled-related protein ocular phenotype and
      glycogen storage disease type Ib.
AB  - AIM: To report co-occurrence of two rare recessive conditions, the membrane
      frizzled-related protein (MFRP)-related ocular phenotype and glycogen storage
      disease type 1b (GSD-1b), in three siblings in an Omani family. BACKGROUND:
      Biallelic mutations in the MFRP gene (chromosome 11q23) result in a distinct
      ocular phenotype characterized by retinitis pigmentosa, foveoschisis, optic nerve
      head drusen, and posterior microphthalmos. GSD-1b is an autosomal-recessive
      disorder caused by mutations in SLC37A4 gene located in the same chromosomal
      region. METHODS: An Omani family with three siblings diagnosed with GSD-1b
      presented with ocular manifestations of progressive visual impairment and
      diminution of night vision. All siblings underwent a standard ophthalmic and
      clinical genetic evaluation. Full sequencing of the MFRP and SLC37A4 genes and
      haplotype analysis was carried out. RESULTS: The three children (2F:1M) aged 13,
      17, and 18 years were born to consanguineous parents. Their best-corrected visual
      acuity ranged from 20/60 to 20/15. Ophthalmic exam revealed bilateral optic disc
      drusen, foveoschisis, and pigmentary retinopathy, hyperopia of +12 to +15.5
      diopters, and decreased axial length (15.8-16.39 mm) in all affected siblings.
      Full-field electroretinography showed rod-cone dysfunction. Sequence analysis
      revealed two novel variants in a homozygous state in the SLC37A4 and MFRP genes
      in all the affected patients. CONCLUSIONS: We report the MFRP-related ocular
      phenotype in three siblings with GSD-1b. Molecular genetic studies identified
      novel mutations in the MFRP and SLC37A4 genes. Co-inheritance of a haplotype
      harboring mutations in both loci on chromosome 11q23 resulted in co-occurrence of
      the MFRP-related ocular phenotype and GSD-1b. This has not been reported
      previously.

PMID- 28511027
TI  - Ross-Konno Procedure With Cylinder Mitral Valve Replacement in 49 Days Old
      Infant.
AB  - A neonate with antenatally diagnosed severe aortic valve stenosis, left
      ventricular outflow tract obstruction, left ventricular endocardial
      fibroelastosis, and severe mixed mitral valve disease was admitted to our center
      for balloon aortic valvuloplasty. On day 49, we performed a Ross-Konno procedure
      and mitral valve replacement on the baby, whose weight was 3.4 kg. Right
      ventricle-to-pulmonary artery continuity was restored with a handmade trileaflet
      Gore-Tex conduit. We used a handmade cylindrical prosthesis made from
      decellularized equine pericardium in the mitral position. We observed improvement
      in left ventricular function and good performance of aortic, pulmonary, and
      mitral prostheses at four months of follow-up.

PMID- 28511029
TI  - Conceptualizing ethnicity in alcohol and drug research: Epidemiology meets social
      theory.
AB  - Since the 1990s, social scientists have rejected notions of ethnicity as
      something static and discrete, instead highlighting the context-dependent and
      fluid nature of multiple identities. In spite of these developments, researchers
      within the substance use fields continue to assess ethnic group categories in
      ways that suggest little critical reflection in terms of the validity of the
      measurements themselves, nor the social, bureaucratic, and political decisions
      shaping standard measures of ethnicity. This paper highlights these
      considerations, while also acknowledging the role of socially-delineated ethnic
      categorizations in documenting health inequities and social injustices. We call
      on researchers in alcohol and drugs research to critically appraise their use of
      ethnic categorizations, querying how to best measure ethnicity within their own
      studies in ways that are justified beyond simplified explanations of social
      convention and that "do no harm" in terms of perpetuating racism and obscuring
      the roots causes of social and health problems related to alcohol and drugs.

PMID- 28511031
TI  - Modeling the mental health service utilization decisions of university
      undergraduates: A discrete choice conjoint experiment.
AB  - OBJECTIVE: We modeled design factors influencing the intent to use a university
      mental health service. PARTICIPANTS: Between November 2012 and October 2014, 909
      undergraduates participated. METHOD: Using a discrete choice experiment,
      participants chose between hypothetical campus mental health services. RESULTS:
      Latent class analysis identified three segments. A Psychological/Psychiatric
      Service segment (45.5%) was most likely to contact campus health services
      delivered by psychologists or psychiatrists. An Alternative Service segment
      (39.3%) preferred to talk to peer-counselors who had experienced mental health
      problems. A Hesitant segment (15.2%) reported greater distress but seemed less
      intent on seeking help. They preferred services delivered by psychologists or
      psychiatrists. Simulations predicted that, rather than waiting for standard
      counseling, the Alternative Service segment would prefer immediate access to E
      Mental health. The Usual Care and Hesitant segments would wait 6 months for
      standard counseling. CONCLUSIONS: E-Mental Health options could engage students
      who may not wait for standard services.

PMID- 28511030
TI  - Emotional approach coping and depressive symptoms in colorectal cancer patients:
      The role of the intimate relationship.
AB  - This study examined whether emotional approach coping was associated with lower
      depressive symptoms, and whether intimacy moderated this association, in 121
      married/partnered colorectal cancer (CRC) outpatients. Prospective analyses of
      survey data on emotional approach coping, depressive symptoms, and intimacy
      measured at baseline and 6-month follow-up showed that depressive symptoms were
      inversely related to processing, expression, and intimacy. At baseline, the
      association between processing and depressive symptoms was moderated by intimacy:
      greater processing was associated with lower depressive symptoms only for those
      in relatively high-intimacy relationships. Enhancing emotional approach coping
      efforts and relationship quality may benefit CRC patients' adjustment.

PMID- 28511032
TI  - Correlates of health-related quality of life in patients with myocardial
      infarction: A literature review.
AB  - BACKGROUND: By the increasing emphasis on health-related quality of life (HRQoL)
      in patients with myocardial infarction (MI), it is necessary to explore factors
      that affect HRQoL in this population. OBJECTIVES: This study aimed to identify
      correlates of HRQoL in patients with MI. DESIGN: A literature review of the
      factors that affect HRQoL in patients with MI (1995-2016). DATA SOURCES: Three
      main databases-CINAHL, MEDLINE and PsychINFO-were searched to retrieve relevant
      peer-reviewed articles published in English. REVIEW METHODS: In consultation with
      a medical librarian, we identified relevant MeSH terms and used them for
      searching the literature: health-related quality of life/quality of
      life/HRQoL/QoL, myocardial infarction/heart attack/MI and predict*/factor. Data
      elements were extracted and narratively described variables synthesised into four
      categories. RESULTS: A total of 48 studies met the inclusion criteria and were
      included in the review. Correlates of HRQoL in patients with MI were identified
      in the following categories: demographic, behavioural, disease-related, and
      psychosocial factors. Specific correlates included age and gender-identity for
      demographic factors; physical activity and smoking for behavioural factors;
      severity of MI, symptoms, and comorbidities for disease-related factors; anxiety
      and depression for psychosocial factors. CONCLUSIONS: Identifying correlates of
      HRQoL can help identify patients who are at risk for poor HRQoL in the recovery
      or rehabilitation stage of post-MI. Future intervention should focus on
      adjustable correlates such as behavioural and psychosocial factors to promote
      HRQoL among patients after experiencing MI.

PMID- 28511033
TI  - Comparing adult cannabis treatment-seekers enrolled in a clinical trial with
      national samples of cannabis users in the United States.
AB  - BACKGROUND: Cannabis use rates are increasing among adults in the United States
      (US) while the perception of harm is declining. This may result in an increased
      prevalence of cannabis use disorder and the need for more clinical trials to
      evaluate efficacious treatment strategies. Clinical trials are the gold standard
      for evaluating treatment, yet study samples are rarely representative of the
      target population. This finding has not yet been established for cannabis
      treatment trials. This study compared demographic and cannabis use
      characteristics of a cannabis cessation clinical trial sample (run through
      National Drug Abuse Treatment Clinical Trials Network) with three nationally
      representative datasets from the US; 1) National Survey on Drug Use and Health,
      2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3)
      Treatment: Episodes Data Set - Admissions. METHODS: Comparisons were made between
      the clinical trial sample and appropriate cannabis using sub-samples from the
      national datasets, and propensity scores were calculated to determine the degree
      of similarity between samples. RESULTS: showed that the clinical trial sample was
      significantly different from all three national datasets, with the clinical trial
      sample having greater representation among older adults, African Americans,
      Hispanic/Latinos, adults with more education, non-tobacco users, and daily and
      almost daily cannabis users. CONCLUSIONS: These results are consistent with
      previous studies of other substance use disorder populations and extend sample
      representation issues to a cannabis use disorder population. This illustrates the
      need to ensure representative samples within cannabis treatment clinical trials
      to improve the generalizability of promising findings.

PMID- 28511035
TI  - On the context dependency of implicit self-esteem in social anxiety disorder.
AB  - BACKGROUND AND OBJECTIVES: Cognitive models assume that negative self-evaluations
      are automatically activated in individuals with Social Anxiety Disorder (SAD)
      during social situations, increasing their individual level of anxiety. This
      study examined automatic self-evaluations (i.e., implicit self-esteem) and state
      anxiety in a group of individuals with SAD (n = 45) and a non-clinical comparison
      group (NC; n = 46). METHODS: Participants were randomly assigned to either a
      speech condition with social threat induction (giving an impromptu speech) or to
      a no-speech condition without social threat induction. We measured implicit self
      esteem with an Implicit Association Test (IAT). RESULTS: Implicit self-esteem
      differed significantly between SAD and NC groups under the speech condition but
      not under the no-speech condition. The SAD group showed lower implicit self
      esteem than the NC group under the speech-condition. State anxiety was
      significantly higher under the speech condition than under the no-speech
      condition in the SAD group but not in the NC group. Mediation analyses supported
      the idea that for the SAD group, the effect of experimental condition on state
      anxiety was mediated by implicit self-esteem. LIMITATIONS: The causal relation
      between implicit self-esteem and state anxiety could not be determined.
      CONCLUSION: The findings corroborate hypotheses derived from cognitive models of
      SAD: Automatic self-evaluations were negatively biased in individuals with SAD
      facing social threat and showed an inverse relationship to levels of state
      anxiety. However, automatic self-evaluations in individuals with SAD can be
      unbiased (similar to NC) in situations without social threat.

PMID- 28511034
TI  - School collective occupation movements and substance use among adolescents: A
      school-level panel design.
AB  - BACKGROUND: Recently, social movements across the world have demanded reforms to
      education systems and other institutions. Although such movements have affected
      large numbers of people across multiple countries, we know little about the
      impacts they have had on population health. We focus on one example: the massive
      strikes and collective occupation of secondary schools across Chile, which
      occurred contemporaneously with a large increase in marijuana use among students
      in this age group. We aimed to evaluate the causal effects that the 2011 Chilean
      school strikes had on adolescent substance use, including the initiation of
      marijuana use and the use of alcohol and marijuana. METHODS: School-level,
      aggregated panel design using data from the National Drug Surveys among Secondary
      Students from 2005 to 2015 for students in grades 9-12. We used a fixed-effects
      difference-in-difference model to estimate the effect of school occupations on
      prevalence of self-reported indicators of drug use. RESULTS: Reported marijuana
      use doubled between 2009 and 2013 among Chilean adolescents. After controlling
      for secular trends in outcomes and for school characteristics, there was no
      evidence of increased marijuana initiation, alcohol and marijuana use, or of an
      increase in heavy use among adolescents being directly attributable to school
      strikes and occupations in 2011. CONCLUSIONS: The 2011 Occupy school movement in
      Chile had no detectable causal effect on substance use among Chilean adolescents.
      The increase in marijuana use from 2009 to 2013 seems to be part of broader
      social changes occurring among the school-age population.

PMID- 28511036
TI  - Proliferation.

PMID- 28511037
TI  - Role of pH and ionic strength in the aggregation of TiO2 nanoparticles in the
      presence of extracellular polymeric substances from Bacillus subtilis.
AB  - Increased use of commercial titanium dioxide nanoparticles (TiO2 NPs) in consumer
      products most likely leads to their additional environmental release. Aggregation
      and disaggregation processes are expected to play an important role in the fate
      and transport of TiO2 NPs in natural aquatic ecosystems. Therefore, in this work,
      we have studied the colloidal stability of TiO2 NPs in the presence of
      extracellular polymeric substances (EPS) from Bacillus subtilis and the
      adsorption behavior of EPS on TiO2 NPs in aqueous solutions at different pH
      values and ionic strengths (IS). The adsorption and aggregation processes were
      found to depend on the solution chemistry. The mass fraction of EPS on TiO2 NPs
      decreased with increased pH and NaCl concentrations, which was verified by
      Fourier transform infrared spectroscopy. The presence of EPS can substantially
      influence the colloidal stability of TiO2 NPs. In deionized water, the
      aggregation of NPs was induced by the addition of EPS only when the pH was below
      the TiO2 NP point of zero charge (~6). When the pH was equal to pHPZC, TiO2, the
      TiO2 NPs would rapidly form large aggregates, but the adsorption of EPS leads to
      partial fragmentation via electrostatic repulsion and steric hindrance. When the
      pH was greater than pHPZC, TiO2, the aggregation rate was minimally affected by
      the increased EPS concentration. In NaCl solution, the aggregation rate of TiO2
      NPs obviously increased with increased NaCl concentration. The critical
      coagulation concentration (CCC) of TiO2 NPs is 13.9 mM in the absence of EPS and
      increases to 155.6, 213.7 and 316.4 mM in the presence of 1, 5 and 10 mg/L EPS in
      NaCl solution, respectively, which indicates that the steric hindrance occurs
      after the addition of EPS. This study suggests that environmental conditions and
      EPS concentration greatly modify the colloidal stability of TiO2 nanoparticles.

PMID- 28511038
TI  - Attributable risks of emergency hospital visits due to air pollutants in China: A
      multi-city study.
AB  - Air pollution is associated with risks of mortality in China, but the evidence is
      still limited for morbidity. This study aims to examine overall effects of
      ambient air pollutants on emergency hospital visits (EHVs) at the national level
      in China and calculate corresponding attributable risks. We collected daily data
      for EHVs from 33 largest hospitals in China between Oct 2013 and Dec 2014, as
      well as daily measurements of particulate matter (PM10 and PM2.5: particles with
      aerodynamic diameter < 10 MUm and 2.5 MUm, respectively), nitrogen dioxide (NO2)
      and sulphur dioxide (SO2) from 31 cities where the hospitals were located.
      Firstly, quasi-Poisson regression with a constrained distributed lag model (CDLM)
      was employed to examine city-specific associations of EHVs with each pollutant.
      Then, the effects at the national scale were pooled with a random-effect meta
      analysis. Daily EHVs was significantly associated with a 10 MUg/m3 increase in
      PM2.5 at lag 0-2 days [cumulative relative risk (RR) and 95% confidence intervals
      (CI): 1.006 (1.002, 1.009)], PM10 at lag 0-1 days [1.004 (1.002, 1.006)], NO2 at
      lag 0-1 days [1.015 (1.010, 1.019)] and SO2 at lag 0-2 days [1.022 (1.014,
      1.030)]. The effect estimates were not modified by sex, but stronger effects were
      observed among children than adults. Overall, 3.34% of EHVs may result from
      exposure to ambient PM2.5, 3.96% to PM10, 5.90% to NO2 and 5.38% to SO2. Exposure
      to outdoor air pollution has acute effects on EHVs. Effective measures to control
      air pollution levels in China could potentially reduce demands for emergency
      hospital services.

PMID- 28511039
TI  - Occurrence, composition, source, and regional distribution of halogenated flame
      retardants and polybrominated dibenzo-p-dioxin/dibenzofuran in the soils of
      Guiyu, China.
AB  - Guiyu, China, is well-known for the crude disposal of electronic waste (EW) and
      severe persistent organic pollutants (POPs). Therefore, in this study, the
      occurrence, composition, and source of polybrominated diphenyl ethers (PBDEs),
      2,2',4,4',5,5'-hexabromobiphenyl (BB153), some novel brominated flame retardants
      (NBFRs), Dechlorane Plus (DP) and polybrominated dibenzo-p-dioxins/dibenzofurans
      (PBDD/Fs) in farmland soils covering Guiyu were studied. In EW disposal area
      soils, PBDEs were the most abundant FRs, with concentrations of 13-1014 ng g-1.
      The primary PBDE sources were technical Penta- and Deca-BDE mixtures in northern
      and southern Guiyu, respectively. The levels of BB153 were relatively low,
      possibly because it has been banned in the 1970s. The concentrations of
      hexabromobenzene (HBB) were 0.048-3.3 ng g-1, while pentabromoethylbenzene (PBEB)
      was almost not detected in the soils. Two alternatives to commercial PBDEs,
      decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy) ethane
      (BTBPE), were the primary NBFRs, with concentrations of 1.8-153 ng g-1 and 0.43
      15 ng g-1, respectively. DP was another primary FR, with concentrations of 0.57
      146 ng g-1. Moreover, syn-DP and anti-DP isomers were not stereoselectively
      decomposed during the EW disposal process and were therefore present in their
      original fractions in the soils. The levels of PBDD/Fs in EW disposal area soils
      were 2.5-17 pg TEQ g-1. 1,2,3,4,6,7,8-HpBDF and OBDF were the dominant congeners,
      mainly derived from processing, pyrolysis and combustion of BFRs. The regional
      distribution of pollutants was shown to be related to the disposal manner of EW,
      with their open thermal disposal tending to release more highly brominated
      compounds such as BDE209, DBDPE, and 1,2,3,4,6,7,8-HpBDF. Additionally, some
      riverbank sites were heavily polluted because of nearby point sources, downwind
      Simapu (SMP) town without EW disposal activity was also contaminated by these
      pollutants.

PMID- 28511040
TI  - Removal of selected PPCPs, EDCs, and antibiotic resistance genes in landfill
      leachate by a full-scale constructed wetlands system.
AB  - Landfill leachate could be a significant source of emerging contaminants (ECs)
      and antibiotic resistance genes (ARGs) into the environment. This study provides
      the first information on the occurrence of selected ECs and ARGs in raw leachate
      from 16-year old closed landfill site in Singapore. Among the investigated ECs,
      acetaminophen (ACT), bisphenol A (BPA), clofibric acid (CA), caffeine (CF),
      crotamiton (CTMT), diclofenac (DCF), N,N-diethyl-m-toluamide (DEET), gemfibrozil
      (GFZ), lincomycin (LIN), salicylic acid (SA), and sulfamethazine (SMZ) were the
      most frequently detected compounds in raw landfill leachate. The concentrations
      of detected ECs in raw landfill leachate varied significantly, from below
      quantification limit to 473,977 ng/L, depending on the compound. In this study,
      Class I integron (intl1) gene and ten ARGs were detected in raw landfill
      leachate. Sulfonamide resistance (sul1, sul2, and dfrA), aminoglycoside
      resistance (aac6), tetracycline resistance (tetO), quinolone resistance (qnrA),
      and intl1 were ubiquitously present in raw landfill leachate. Other resistance
      genes, such as beta-lactam resistance (blaNMD1, blaKPC, and blaCTX) and macrolide
      lincosamide resistance (ermB) were also detected, detection frequency of <50%.
      The removal of target ECs and ARGs by a full-scale hybrid constructed wetland
      (CW) was also evaluated. The vast majority of ECs exhibited excellent removal
      efficiencies (>90%) in the investigated hybrid CW system. This hybrid CW system
      was also found to be effective in the reduction of several ARGs (intl1, sul1,
      sul2, and qnrA). Aeration lagoons and reed beds appeared to be the most important
      treatment units of the hybrid CW for removing the majority of ECs from the
      leachate.

PMID- 28511041
TI  - Biofilm formation and granule properties in anaerobic digestion at high salinity.
AB  - For the anaerobic biological treatment of saline wastewater, Anaerobic Digestion
      (AD) is currently a possibility, even though elevated salt concentrations can be
      a major obstacle. Anaerobic consortia and especially methanogenic archaea are
      very sensitive to fluctuations in salinity. When working with Upflow Sludge
      Blanket Reactor (UASB) technology, in which the microorganisms are aggregated and
      retained in the system as a granular biofilm, high sodium concentration
      negatively affects aggregation and consequently process performances. In this
      research, we analysed the structure of the biofilm and granules formed during the
      anaerobic treatment of high salinity (at 10 and 20 g/L of sodium) synthetic
      wastewater at lab scale. The acclimated inoculum was able to accomplish high
      rates of organics removal at all the salinity levels tested. 16S rRNA gene clonal
      analysis and Fluorescence In Situ Hybridization (FISH) analyses identified the
      acetoclastic Methanosaeta harundinacea as the key player involved acetate
      degradation and microbial attachment/granulation. When additional calcium (1 g/L)
      was added to overcome the negative effect of sodium on microbial aggregation,
      during the biofilm formation process microbial attachment and acetate degradation
      decreased. The same result was observed on granules formation: while calcium had
      a positive effect on granules strength when added to UASB reactors, Methanosaeta
      filaments were not present and the degradation of the partially acidified
      substrate was negatively influenced. This research demonstrated the possibility
      to get granulation at high salinity, bringing to the forefront the importance of
      a selection towards Methanosaeta cells growing in filamentous form to obtain
      strong and healthy granules.

PMID- 28511042
TI  - Controllable synthesis of hierarchical MnOx/TiO2 composite nanofibers for
      complete oxidation of low-concentration acetone.
AB  - A novel hierarchical MnOx/TiO2 composite nanofiber was fabricated by combining
      the electrospinning technique and hydrothermal growth method. The synthesized
      nanomaterial, which comprised primary TiO2 nanofibers and secondary MnOx
      nanoneedles, was further investigated for complete catalytic oxidation of
      volatile organic compounds for the first time, and this presented high-oxidation
      performance on low-concentration acetone. The morphological, structural,
      physicochemical characterization, and catalytic performance analyses demonstrated
      that the highest catalytic activity was achieved from the obtained MnOx/TiO2
      nanofiber catalyst with 30wt.% manganese loading. This finding can be ascribed to
      the synergistic effect of the specific hierarchical nanofibrous morphology, the
      abundant surface-adsorbed oxygen, the superior redox property, and the sufficient
      specific surface.

PMID- 28511044
TI  - Bentonite modified with zinc enhances aflatoxin B1 adsorption and increase
      survival of fibroblasts (3T3) and epithelial colorectal adenocarcinoma cells
      (Caco-2).
AB  - Bentonites are commonly used as feed additives to reduce the bioavailability and
      thus the toxicity of aflatoxins by adsorbing the toxins in the gastrointestinal
      tract. Aflatoxins are particular harmful mycotoxins mainly found in areas with
      hot and humid climates. They occur in food and feedstuff as a result of fungal
      contamination before and after harvest. The aim of this study was to modify
      Brazilian bentonite clay by incorporation of zinc (Zn) ions in order to increase
      the adsorption capacity and consequently reduce the toxicity of aflatoxins. The
      significance of Zn intercalating conditions such as concentration, temperature
      and reaction time were investigated. Our results showed that the Zn treatment of
      the bentonite increased the aflatoxin B1 (AFB1) adsorption and that Zn
      concentration had a negative effect. Indeed, temperature and time had no
      significant effect in the binding capacity. The modified bentonite (Zn-Bent1) was
      not cytotoxic to either fibroblasts (3T3) nor epithelial colorectal
      adenocarcinoma cells (Caco-2) cell lines. Interestingly, Zn-Bent1 has higher
      protective effect against AFB1 induced cytotoxicity than the unmodified
      bentonite. In conclusion, the Zn modified bentonite, Zn-Bent1, represent an
      improved tool to prevent aflatoxicosis in animals fed on AFB1 contaminated feed.

PMID- 28511043
TI  - Environmental behavior of 12 UV filters and photocatalytic profile of ethyl-4
      aminobenzoate.
AB  - Ethyl-4-aminobenzoate (Et-PABA) is currently used as a substitute for 4
      aminobenzoate (PABA) in sunscreens and anesthetic ointments. Despite its
      widespread use and hydrophilicity, Et-PABA has never been found in environmental
      waters. This study, probed the occurrence of Et-PABA in both seawater and
      drinking water sources in Hong Kong, and evaluated its transformation products
      (TPs) and environmental fate via cumulative potency and photocatalytic profile
      analyses. Another 11 UV filters used in skin-care products were also studied. Et
      PABA was not detected in any water sample. Four other UV filters were dominant at
      ng/L level in both seawater and drinking water sources. UHPLC-QTOF-MS was used to
      elucidate the structure of TPs. With high resolution accurate mass data and
      fragment rationalization, 11 Et-PABA TPs were characterized, including seven
      intermediates firstly proposed as TPs; two compounds were reported for the first
      time. It is proposed that photocatalysis induces transformation pathways of
      (de)hydroxylation, demethylation and molecular rearrangement. Luminescent
      bacteria tests showed decreasing toxicity with increasing irradiation of Et-PABA,
      suggesting that irradiation TPs are less toxic than the parent compound.
      Transformation of Et-PABA appears to explain why Et-PABA has not been detected in
      the natural environment.

PMID- 28511045
TI  - Stigma and diurnal cortisol among transitioning transgender men.
AB  - This study assessed diurnal cortisol functioning in relation to stigma-based
      transition-specific stressors experienced by transgender men during their
      transition from female to male. Sixty-five healthy transgender men undergoing
      testosterone therapy participated in in-person interviews through which
      transition-specific stressors were identified. Interviews were coded according to
      participant reported (1) Transitioning-identity stress; (2) Coming Out stress;
      (3) Gender-specific Public Bathroom stress; and (4) levels of general Perceived
      Stress. Participants provided fifteen salivary samples assessing cortisol diurnal
      rhythm over three days. Hierarchical linear models, adjusted for duration of time
      on testosterone therapy, body mass index, steroid-related medication use, mean
      awakening time, and CAR, confirmed that elevated diurnal cortisol levels at
      awakening were associated with transition-specific social stressors including
      experiencing Transitioning-identity stress, frequent Coming Out stress, and
      Gender-specific Public Bathroom stress. Transitioning-identity stress and Gender
      specific Public Bathroom stress also predicted a steeper negative slope at
      awakening. General Perceived Stress was not associated with elevated cortisol or
      slope. These results clarify the relation of increased cortisol at awakening with
      a negative linear slope to perceived stigma and transition-related stress
      experience among transgender men.

PMID- 28511046
TI  - Effects of stress on women's preference for male facial masculinity and their
      endocrine correlates.
AB  - Women's preferences for masculinity in men's faces seem to vary across the
      menstrual cycle and are assumed to be strongest around ovulation. A number of
      hormones have been proposed to underlie these subtle cyclic shifts. Furthermore,
      mating preferences are context-dependent, and stress has been found to alter mate
      choice, both in animals and humans. Currently, the effects of stress on women's
      preference for masculinity remain unknown. To examine the hormonal basis and the
      impact of stress on facial masculinity preference, we tested for within-subject
      changes in 52 healthy young women who underwent the Trier Social Stress Test
      (TSST) and the placebo-TSST in randomized order in the late follicular and mid
      luteal phases of their menstrual cycle. Menstrual cycle phase and hormone levels
      were confirmed using estradiol, testosterone, progesterone, and cortisol analyses
      from saliva. Results show that women were more likely to be attracted to
      masculine-faced men right before ovulation than in the mid-luteal phase.
      Estradiol modulated this masculinity preference with high estradiol levels being
      related to stronger masculinity preference. When stressed however, women
      experienced a decrease in male facial masculinity preference. In line with these
      findings, the higher the cortisol increase to stress, the less were masculine
      faces preferred to more feminine faces. Mate choice is a central component of
      reproduction. The present results provide information about the effects of stress
      and hormonal influences on mate preferences in women.

PMID- 28511047
TI  - Birth weight and postnatal growth in preterm born children are associated with
      cortisol in early infancy, but not at age 8 years.
AB  - BACKGROUND: Preterm birth has been associated with altered hypothalamic-pituitary
      adrenal (HPA-) axis activity as well as cardiometabolic diseases and
      neurodevelopmental impairments later in life. We assessed cortisol from term age
      to age 8 y in children born preterm, to explore the development of HPA-axis
      activity in association with intrauterine and early-postnatal growth until 6 mo.
      corrected age. METHODS: In 152 children born at a gestational age <=32 wks.
      and/or with a birth weight <=1,500g, random serum cortisol was assessed at term
      age (n=150), 3 mo. (n=145) and 6 mo. corrected age (n=144), and age 8 y (n=59).
      Salivary cortisol was assessed at age 8 y (n=75): prior to bedtime, at awakening,
      15min after awakening, and before lunch. Cortisol was analyzed in association
      with birth weight-standard deviation score (SDS), being born small for
      gestational age (SGA), and combinations of intrauterine and postnatal growth:
      appropriate for gestational age (AGA) with or without growth restriction (AGA GR+
      or AGA GR-) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA
      CUG+ or SGA CUG-) at 6 mo. corrected age. Cross-sectional associations at all
      time points were analyzed using linear regression, and longitudinal associations
      were analyzed using generalized estimating equations. RESULTS: Longitudinally,
      birth weight-SDS was associated with cortisol (beta [95%CI]): lower cortisol over
      time was seen in infants with a birth weight <=-2 SDS (-50.69 [-94.27; -7.11],
      p=0.02), infants born SGA (-29.70 [-60.58; 1.19], p=0.06), AGA GR+ infants (
      55.10 [-106.02; -4.17], p=0.03) and SGA CUG- infants (-61.91 [-104.73; -19.10],
      p=0.01). In cross-sectional analyses at age 8 y, no associations were found
      between either serum or salivary cortisol and birth weight-SDS, SGA-status, or
      growth from birth to 6 mo. corrected age. CONCLUSION: In children born preterm,
      poor intrauterine and postnatal growth were associated with lower cortisol in
      early infancy, but not at age 8 y. Even though HPA-axis activity no longer
      differed between groups at age 8 y, or differences could not be confirmed due to
      attrition, it is unknown whether the differences found in early infancy could
      attribute to increased health risks later in life.

PMID- 28511048
TI  - Defensive freezing links Hypothalamic-Pituitary-Adrenal-axis activity and
      internalizing symptoms in humans.
AB  - The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the
      expression of defensive freezing. Adaptive freezing reactivity, characterized by
      an immediate increase in acute stress and timely termination upon threat offset
      or need to act, is essential for adequate stress coping. Blunted HPA-axis
      activity in animals is associated with blunted freezing reactivity and
      internalizing symptoms. Despite their potential relevance, it remains unknown
      whether these mechanisms apply to humans and human psychopathology. Using a well
      established method combining electrocardiography and posturography, we assessed
      freezing before, immediately after, and one hour after a stress induction in 92
      human adolescents. In line with animal models, human adolescents showed stress
      induced freezing, as quantified by relative reductions in heart rate and body
      sway after, as compared to before, stress. Moreover, relatively lower basal
      cortisol was associated with reduced stress-induced freezing reactivity (i.e.,
      less immediate freezing and less recovery). Path analyses showed that decreased
      freezing recovery in individuals with reduced cortisol levels was associated with
      increased levels of internalizing symptoms. These findings suggest that reduced
      freezing recovery may be a promising marker for the etiology of internalizing
      symptoms.

PMID- 28511049
TI  - The Omega-3 Index and relative risk for coronary heart disease mortality:
      Estimation from 10 cohort studies.
AB  - BACKGROUND AND AIMS: A recent 19-cohort meta-analysis examined the relationships
      between biomarkers of omega-3 fatty acids and risk for coronary heart disease
      (CHD). That study did not, however, report hazard ratios (HRs) specifically as a
      function of erythrocyte eicosapentaenoic (EPA) plus docosahexaenoic (DHA) levels,
      a metric called the Omega-3 Index in which EPA + DHA content is expressed as a
      percent of total fatty acids. The Omega-3 Index has been used in several recent
      studies and is a validated biomarker of omega-3 fatty acid tissue levels, but
      additional data are needed to confirm (or refute) the originally-proposed
      clinical cut-points of <4% (higher risk) and 8%-12% (lower risk). METHODS: The
      present study was therefore undertaken using published data from this meta
      analysis to estimate HRs per 1-SD increase in the Omega-3 Index and median
      quintile values for this metric across 10 of the cohorts for which the needed
      data were available. RESULTS: The overall mean (SD) for the Omega-3 Index in
      these 10 cohort studies was 6.1% (2.1%), and the HR for a 1-SD increase was 0.85
      (95% confidence interval, 0.80-0.91). Median quintile 1 and 5 levels were 4.2%
      vs. 8.3%, respectively. Based on these values, we estimate that risk for fatal
      CHD would have been reduced by about 30% moving from an Omega-3 Index of 4%-8%.
      CONCLUSIONS: These findings support the use of <4% and >8% as reasonable
      therapeutic targets for the Omega-3 Index.

PMID- 28511050
TI  - Maternal distress in late pregnancy alters obstetric outcomes and the expression
      of genes important for placental glucocorticoid signalling.
AB  - The experience of maternal distress in pregnancy is often linked with poorer
      obstetric outcomes for women as well as adverse outcomes for offspring.
      Alterations in placental glucocorticoid signalling and subsequent increased fetal
      exposure to cortisol have been suggested to underlie this relationship. In the
      current study, 121 pregnant women completed the Perceived Stress Scale, State
      Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale in the third
      trimester of pregnancy. Placental samples were collected after delivery. Maternal
      history of psychiatric illness and miscarriage were significant predictors of
      poorer mental health in pregnancy. Higher anxiety was associated with an increase
      in women delivering via elective Caesarean Section, and an increase in bottle
      feeding. Birth temperature was mildly reduced among infants of women with high
      levels of depressive symptomology. Babies of mothers who scored high in all
      stress (cumulative distress) measures had reduced 5-min Apgar scores. High
      cumulative distress reduced the expression of placental HSD11B2 mRNA and
      increased the expression of placental NR3C1 mRNA. These data support a role for
      prenatal distress as a risk factor for altered obstetric outcomes. The
      alterations in placental gene expression support a role for altered placental
      glucocorticoid signalling in the relationship between maternal prenatal distress
      and adverse outcomes.

PMID- 28511051
TI  - A one-year longitudinal qualitative study of peer support services in a non
      Western context: The perspectives of peer support workers, service users, and co
      workers.
AB  - This study explored the changing views of key stakeholders (peer support workers,
      their co-workers, and service users) about peer support services in a non-Western
      community, using a longitudinal qualitative approach. Five trainee peer support
      workers (PSWs), 15 service users, and 14 co-workers were interviewed over a 12
      month period, under the auspices of the Peer Support Workers Project (also known
      as the Mindset project) in Hong Kong. A total of 77 interviews were transcribed
      and thematic analyses were conducted across the participant groups at three
      different time points (training, work placements, and employment). During the
      initial implementation of the services, uncertainty about the role of the PSWs
      were reported. However, trusting and beneficial relationships with service users
      were gradually built, showing growing resilience and confidence over time. The
      participants realized that PSWs' experiences of mental illnesses were a unique
      asset that could help service users to alleviate their own somatic symptoms and
      improve their connections with others. Our findings highlight that the
      perceptions of peer support services changed from confusion to viewing PSWs as an
      asset, to an awareness of the importance of family support, and to the belief
      that implementing such a program will benefit both service users and PSWs.

PMID- 28511053
TI  - Opioid analgesics and heroin: Examining drug misuse trends among a sample of drug
      treatment clients in Kentucky.
AB  - BACKGROUND: In an effort to mitigate Kentucky's prescription drug misuse,
      legislative intervention efforts were introduced in 2012 and 2013 to better
      regulate pain clinics, prescribed use of opioid analgesics, and to expand the
      monitoring of opioid prescriptions. The focus of this paper is primarily on
      opioid analgesics and heroin and the relationship of use/misuse patterns of these
      drugs to state drug policy initiatives. METHODS: A secondary data analysis of
      drug treatment clients (N=52,360) was conducted to project illicit drug use
      trends in Kentucky. This study describes temporal and geographic trends of self
      reported illicit drug use among individuals in state-funded treatment in Kentucky
      between fiscal year 2010 and fiscal year 2013. RESULTS: Significant reductions in
      the prevalence of illicit opioid use, declined from fiscal year 2010 to fiscal
      year 2013 (p<.01, CI=-.298 to -.215). However, heroin use rates significantly
      increased over the years studied, suggesting there may be a transition from
      prescription opioids to heroin (p<.01, CI=.143 to .178). The analysis suggests
      these trends may continue. CONCLUSIONS: Findings suggest Kentucky's legislative
      efforts were effective in reducing illicit prescription opioid use, but heroin
      use has increased. One possible explanation for this relationship is that as
      prescription opioids became more difficult to obtain, users turned to heroin as a
      substitute. The finding of rising heroin use suggests a need for further policy
      initiatives to reduce heroin use, but the potential effectiveness of this policy
      remains unclear. Understanding trends may help to guide future policy efforts and
      pain management treatment strategies to where they might have their greatest
      impact.

PMID- 28511052
TI  - Phosphate regulates chondrogenesis in a biphasic and maturation-dependent manner.
AB  - Inorganic phosphate (Pi) has been recognized as an important signaling molecule
      that modulates chondrocyte maturation and cartilage mineralization. However,
      conclusive experimental evidence for its involvement in early chondrogenesis is
      still lacking. Here, using high-density monolayer (2D) and pellet (3D) culture
      models of chondrogenic ATDC5 cells, we demonstrate that the cell response to Pi
      does not correlate with the Pi concentration in the culture medium but is better
      predicted by the availability of Pi on a per cell basis (Pi abundance). Both
      culture models were treated with ITS+, 10mM beta-glycerophosphate (betaGP), or
      ITS+/10mM betaGP, which resulted in three levels of Pi abundance in cultures:
      basal (Pi/DNA <10ng/ug), moderate (Pi/DNA=25.3 - 32.3ng/ug), and high abundance
      (Pi/DNA >60ng/ug). In chondrogenic medium alone, the abundance levels were at the
      basal level in 2D culture and moderate in 3D cultures. The addition of 10mM
      betaGP resulted in moderate abundance in 2D and high abundance in 3D cultures.
      Moderate Pi abundance enhanced early chondrogenesis and production of aggrecan
      and type II collagen whereas high Pi abundance inhibited chondrogenic
      differentiation and induced rapid mineralization. Inhibition of sodium phosphate
      transporters reduced phosphate-induced expression of chondrogenic markers. When
      3D ITS+/betaGP cultures were treated with levamisole to reduce ALP activity, Pi
      abundance was decreased to moderate levels, which resulted in significant
      upregulation of chondrogenic markers, similar to the response in 2D cultures.
      Delay of phosphate delivery until after early chondrogenesis occurs (7 days) no
      longer enhanced chondrogenesis, but instead accelerated hypertrophy and
      mineralization. Together, our data highlights the dependence of chondroprogenitor
      cell response to Pi on its availability to individual cells and the chondrogenic
      maturation stage of these cells and suggest that appropriate temporal delivery of
      phosphate to ATDC5 cells in 3D cultures represents a rapid model for mechanistic
      studies into the effects of exogenous cues on chondrogenic differentiation,
      chondrocyte maturation, and matrix mineralization.

PMID- 28511054
TI  - Synthesis and in vitro anticancer activity of new 2-thioxo-oxazolidin-4-one
      derivatives.
AB  - BACKGROUND: Oxazolidinones derivatives exhibit different biological properties,
      including anticancer activity. This work aimed to investigate the anticancer
      potential of five novel 2-Thioxo-oxazolidin-4-one derivatives. METHODS:
      Cytotoxicity assays were performed in human peripheral blood mononuclear cells
      (PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection
      and cell cycle were evaluated by flow cytometry and the expression of genes
      involved in cell death processes by Real-Time PCR. RESULTS: All oxazolinedione
      derivatives were not cytotoxic in PBMCs. NB-5 showed the best results in cancer
      cells, inhibiting the growth of all tumor cell lines tested. NB-4 exhibited the
      highest cytotoxicity in Jurkat cells (IC50=15.19MUM) and NB-3 showed better
      anticancer effects in HL-60 (17.84MUM). Only NB-4 significantly induced apoptosis
      in acute leukemia cells (p=0.001). All compounds caused a significant increase in
      expression of pro-apoptotic gene BID (p<0.05) and BECN1 (p<0.05). NB-3
      significantly modulated the expression of RIPK3 (p=0.02) and DDIT3 (p=0.014),
      while NB-2 induced an increase of CDKN1A (p=0.03) and NB-4 induced PPARgamma gene
      (p=0.0006). CONCLUSION: NB-5 showed antitumor effects in solid and hematopoietic
      cancer cells, while other derivatives produced higher activity against
      hematopoietic cells. In acute leukemia cells, oxazolidinone derivatives modulated
      the expression of genes involved in apoptosis, ER stress, necroptosis and
      inflammation.

PMID- 28511055
TI  - Professional midwifery in Guatemala: A qualitative exploration of perceptions,
      attitudes and expectations among stakeholders.
AB  - BACKGROUND: Despite recommendations that women give birth with a skilled birth
      attendant (SBA), 70% of births in Guatemala occur outside health facilities with
      informally trained traditional birth attendants (TBAs). To increase SBA in rural,
      indigenous communities, a professional midwifery school accredited by the
      government is scheduled to open in 2017. Drawing from Filby's model on barriers
      to the successful integration of professional midwifery into health systems, this
      paper aims to identify threats - and facilitators-toward professional midwifery's
      re-introduction in Guatemala. METHODS: To elucidate perceptions, attitudes and
      expectations towards professional midwifery, qualitative, in-depth interviews
      were conducted with 32 physicians, nurses, and TBAs in six health centers and
      with key decision makers and professional midwives (PMs) in Guatemala City. We
      conducted open and axial coding in Atlas.ti and performed normative comparisons
      of participants' attitudes, perceptions, and expectations with the National
      Vision for professional midwifery and relative comparisons within and across
      disciplinary subgroups. RESULTS: Unprompted, physicians, nurses and TBAs were
      unable to correctly define professional midwifery. Yet, when professional
      midwifery was defined for them, they expressed willingness to work with PMs,
      seeing them as a needed human resource, instrumental in providing intercultural
      care and strengthening facility relationships with TBAs. Some stakeholders
      anticipated resistance toward PMs due to provider turf issues. Notable
      differences in expectations among all groups included ideas for supervision of
      and by the PMs and the PM's role in monitoring women and conducting births in
      communities alongside TBAs. CONCLUSIONS: Facilitators to professional midwifery's
      success include national political will, stakeholders' uniformity of vision, and
      the potential for improved intercultural care. Barriers are mostly professional
      in nature, including impediments to autonomous practice by PMs, hierarchical
      challenges, and turf issues. A specific road map addressing the identified
      barriers is needed for professional midwifery to succeed in reducing maternal
      health disparities in Guatemala.

PMID- 28511057
TI  - Mapping smokeless powder residue on PVC pipe bomb fragments using total
      vaporization solid phase microextraction.
AB  - Quantitating post-blast explosive residue is not a common practice in crime labs
      as it is typically not legally relevant. There is value in quantitation, however,
      if the distribution of residues on Improvised Explosive Devices (IEDs) can help
      guide future sample collection and/or method development. Total vaporization
      solid phase microextraction gas chromatography mass spectrometry (TV-SPME/GC/MS)
      was used to quantify residues of double-base smokeless powder (DBSP), which
      includes nitroglycerin (NG), diphenylamine (DPA), and ethyl centralite (EC) on
      post-blast PVC pipe bomb fragments. The analytical method could separate the
      three constituents in under 5min with a detection limit under 1ppb, which
      demonstrates high throughput while maintaining high sensitivity. The method was
      optimized for nitroglycerin, as it is the most indicative of DBSP. The average
      mass of nitroglycerin recovered from an entire PVC device was 1.0mg. The average
      mass of diphenylamine recovered was much lower (24MUg) and only one device had
      detectable levels of EC. The typical concentration of NG on any given fragment
      was approximately 15-30ppm (MUg NG/g fragment). However, there was no correlation
      between the mass of a fragment and the mass of residue upon it. Instead, the
      residue was distributed such that the highest concentration of residues was found
      on end cap fragments.

PMID- 28511058
TI  - Stability behavior of antiretroviral drugs and their combinations. 7: Comparative
      degradation pathways of lamivudine and emtricitabine and explanation to their
      differential degradation behavior by density functional theory.
AB  - The interest in this study was to establish comparative degradation behavior of
      lamivudine (3TC) and emtricitabine (FTC) under solution and solid state stress
      conditions. Structurally, the two drugs differ only in terms of additional
      fluorine at 5 position in FTC. Along with the known degradation products of both
      the drugs, one additional degradation product was observed in each case, which
      was characterized by mass spectrometry. Both the drugs degraded via the same
      route, but at a differential rate in acid, base and oxidative stress conditions.
      The variable rate of degradation in acid and base conditions was justified by the
      application of density functional theory (DFT).

PMID- 28511056
TI  - Elimination of Schistosoma mansoni in infected mice by slow release of
      artemisone.
AB  - The current treatment of schistosomiasis is based on the anti-helminthic drug
      praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In
      addition, resistance to PZQ is emerging. We suggest a drug, which could serve as
      a potential alternative or complement to PZQ, and as a means of treating
      infections at earlier, pre-granuloma stage. Derivatives of the peroxidic
      antimalarial drug artemisinin have been indicated as alternatives, because both
      plasmodia and schistosomes are blood-feeding parasites. The mechanism of action
      of artemisinins is related to oxidative effects of the artemisinins on
      intracellular reductants leading to formation of cytotoxic reactive oxygen
      species. We used artemisone, which has improved pharmacokinetics and anti
      plasmodial activity, and reduced toxicity compared to other artemisinins in
      clinical use against malaria. We infected adult mice by subcutaneous injection of
      S. mansoni cercariae (about 200) and treated them at various times post infection
      by the following methods: i. artemisone suspension administered by gavage (400
      450 mg/kg); ii. subcutaneous injection of a gel containing a known concentration
      of artemisone (115-120 mg/kg); iii. subcutaneous insertion of the drug
      incorporated in a solid polymer (56-60 mg/kg); iv. intraperitoneal injection of
      the drug solubilized in DMSO (115-120 mg/kg). Drug administration in polymers was
      performed to enable slow release of the artemisone that was verified in vivo and
      in vitro bioassays using drug-sensitive malaria parasites. We found superior
      strong anti-schistosome effects up to a total reduction of worm number, mainly
      following repetitive treatments with the drug absorbed in the polymers (73.1% and
      95.9% reduction in mice treated with artemisone in gel 7 and 14, and 21, 28 and
      35 days post infection, respectively). The results indicate that artemisone has a
      potent anti-schistosome activity. Its main importance in this context is its
      effectiveness in treating hosts harboring juvenile schistosomes, before egg
      deposition and induction of deleterious immune responses.

PMID- 28511059
TI  - Development and validation of a rapid reversed-phase HPLC method for the
      quantification of monoclonal antibody bevacizumab from polyester-based
      nanoparticles.
AB  - Bevacizumab is a powerful human monoclonal antibody approved worldwide for
      treatment of several types of cancer and ocular diseases due to its potential as
      antiangiogenic drug. Nowadays, in order to improve the monoclonal antibody-based
      therapy, attempts have been focused in the formulation of these biomacromolecules
      into nanoparticles. Thus, the aim of this work was to develop and validate a
      reversed-phase high-performance liquid chromatography with fluorescence detection
      method for the determination of bevacizumab from nanoparticulate systems,
      according to the International Conference on Harmonization guidelines.
      Chromatographic analysis were performed on a RP-C8 column with a mobile phase
      composed by water-0.1% (v/v) TFA and acetonitrile-0.1% (v/v) TFA in gradient mode
      at a flow rate of 1mLmin-1. Results showed that the proposed method is specific,
      linear in the range of 10-100MUgmL-1 (r2=0.9997), accurate (recovery rate
      100.50+/-0.85%), precise at the intraday and inter-day (relative standard
      deviation less than 1.79%) and robust. The detection and quantification limits
      were calculated by specific linear calibration curve with less concentrated
      standard (range of 1-20MUgmL-1). The LOD was 2.16MUgmL-1 and LOQ was 6.55MUgmL-1.
      This method was also successfully used, for the first time, to quantify and
      compare the content of bevacizumab encapsulated into poly(lactic-co-glycolic
      acid)-based nanoparticles before and after lyophilization.

PMID- 28511060
TI  - A comparison study on RNase A oligomerization induced by cisplatin, carboplatin
      and oxaliplatin.
AB  - Cisplatin (CDDP) can form interprotein cross-links, leading to the formation of
      platinated oligomers. A dimer, a trimer and higher oligomers of bovine pancreatic
      ribonuclease (RNase A) obtained upon reaction with CDDP in 1:10 protein to metal
      ratio at 37 degrees C have been previously characterized. Here, we verify the
      ability of carboplatin and oxaliplatin to induce RNase A oligomerization under
      the same experimental conditions. The amount of formed RNase A oligomers was
      compared with that obtained in the reaction of the protein with CDDP. Among the
      three anticancer agents, CDDP is the most reactive and the most effective in
      inhibiting the ribonucleolytic activity of the protein. Oxaliplatin is the least
      potent oligomerization agent. Biophysical characterizations of structure and
      stability of platinated dimers formed in the presence of carboplatin and
      oxaliplatin suggest that they have a similar thermal stability and are more prone
      to dissociation than the corresponding dimer obtained with CDDP. Oligomers
      obtained in the presence of carboplatin are the most active. X-ray structures of
      the monomeric adducts that RNase A forms with the three drugs provide a rational
      basis to explain the different effects of the three anticancer agents on
      enzymatic activity and protein aggregation. Although platinated oligomers of
      RNase A formed upon reaction with CDDP, carboplatin and oxaliplatin retain a
      residual ribonuclease activity, they do not show cytotoxic action, suggesting
      that protein aggregation processes induced by Pt-based drugs can represent a
      collateral drawback, which affects the functional state of protein targets and
      reduces the efficacy of Pt-based drug treatment.

PMID- 28511061
TI  - Uptake of Ga-curcumin derivatives in different cancer cell lines: Toward the
      development of new potential 68Ga-labelled curcuminoids-based radiotracers for
      tumour imaging.
AB  - Thanks to the ability to suppress the proliferation and to kill tumour cells,
      several studies have shown the anti-cancer effects of curcumin (CUR) and its
      derivatives, i.e. diacetylcurcumin (DAC) and bis-dehydroxycurcumin (bDHC). This
      study is focused onto the development of curcuminoid complexes with gallium-68
      employed as potential new radio-labelled probes to detect neoplastic tissues
      through imaging techniques such as positron emission tomography. To this purpose,
      the uptake of three Ga-curcuminoid complexes, namely Ga(CUR)2+, Ga(DAC)2+,
      Ga(bDHC)2+, by various tumour cell lines was compared with the uptake of the same
      compounds by normal human lymphocytes by flow cytometry using the intrinsic
      fluorescence of the curcuminoids. Ga(CUR)2+, and particularly Ga(DAC)2+, showed a
      higher uptake by colorectal carcinoma (HT29) and lymphoma (K562) cell lines than
      lymphocytes, while the uptake of Ga(bDHC)2+ was higher in lymphocytes than in all
      the other cell lines. Based on the fluorescence data, Gallium-68 labelled
      complexes were then tested in HT29 cell line. 68Ga(DAC)2+ showed the highest
      uptake by HT29 cells (higher internalization with a lower externalization) and
      the highest affinity. The obtained results are promising and the findings foster
      further investigation on the development of curcumin-metal-based
      radiopharmaceuticals.

PMID- 28511062
TI  - Structure-activity relationship between Zn2+-chelated alkylated poly(1
      vinylimidazole) and gene transfection.
AB  - The structure-activity relationship between Zn2+-chelated alkylated poly(1
      vinylimidazole) (PVIm) and gene transfection has been demonstrated. From a
      chemical structure perspective, ethylated PVIm (PVIm-Et) chelated the most Zn2+
      ions compared to methylated PVIm (PVIm-Me) and butylated PVIm (PVIm-Bu). The
      resulting Zn2+-chelated PVIm-Et formed more stable complexes with plasmid DNA
      complex than non-chelated PVIm-Et. From a biological activity perspective, the
      Zn2+-chelated PVIm-Et delivered the highest amount of Zn2+ ions inside the cell,
      corresponding to the highest gene transfection. These results suggest that PVIm
      Et is the optimal sequence for the chelation of Zn2+ ions to enhance the gene
      transfection activity. The structure-activity relationship in this study is
      expected to offer a unique molecular design for drug/gene delivery systems.

PMID- 28511063
TI  - Competitive reactions among glutathione, cisplatin and copper-phenanthroline
      complexes.
AB  - A large number of cancers are treated with cisplatin (CDDP). However, its use is
      limited by drug resistance, which is often related to intracellular levels of
      thiol-containing molecules such as glutathione (GSH). The role of GSH in
      cisplatin-resistant cancer cells is still unclear. GSH may form adducts with CDDP
      which results in the deactivation of the drug, and, actually, a high
      intracellular level of GSH was observed in some cisplatin-resistant cancers. To
      overcome drug resistance, CDDP is often administered in combination with one or
      more drugs to exploit a possible synergistic effect. In previous studies, we
      observed that the sensitivity to CDDP of leukemic and ovarian cisplatin-resistant
      cancer cells was restored in the presence of [Cu(phen)2(H2O)](ClO4)2 (C0) (phen
      is 1,10-phenathroline). In order to clarify the possible interactions between GSH
      and CDDP, the reactivity and competitive reactions among CDDP, C0 and GSH in
      binary and ternary mixtures were studied. The investigation was extended also to
      [Cu(phen)(H2O)2(ClO4)2] (C10) and GSSG, the oxidized form of GSH. It was observed
      that CDDP was able to react with the studied copper complexes and with GSH or
      GSSG. However, in mixtures containing CDDP, GSH or GSSG and C0 or C10, only
      copper-glutathione complexes were detected, while no platinum-glutathione adducts
      were found.

PMID- 28511064
TI  - Design, synthesis and evaluation of anticancer activity of ruthenium (II)
      polypyridyl complexes.
AB  - A new ligand PFPIP (PFPIP=2-(2,3,4,5,6-pentafluorophenyl)[4,5-f]imadazo
      [1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes
      [Ru(NN)2(PFPIP)](ClO4)2 (NN=dmb: 4,4'-dimethyl-2,2'-bipyridine, 1; bpy: 2,2'
      bipyridine, 2; phen: 1,10-phenanthroline, 3; dmp: 2,9-dimethyl-1,10
      phenanthroline, 4) were synthesized and characterized by elemental analysis, IR,
      1H NMR, 13C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and
      complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated
      using MTT method (MTT=(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide). Complexes 1, 3 and 4 show moderate cytotoxic effect on the cell growth
      in BEL-7402 cells with IC50 values of 32.1+/-0.9, 37.9+/-1.7 and 42.1+/-3.0MUM,
      respectively. The apoptosis in BEL-7402 cell was investigated with AO/EB and
      Hoechst 33,258 staining methods. The autophagy in BEL-7402 cell induced by
      complexes was assayed using MDC staining cell nuclei. The cell invasion, reactive
      oxygen species (ROS), mitochondrial membrane potential, cell cycle arrest,
      cellular uptake, comet assay and wound healing were studied under a fluorescent
      microscope. The complexes can cause autophagy and inhibit the cell invasion, and
      increase the ROS levels and induce a decrease in the mitochondrial membrane
      potential. The expression of the proteins related with apoptosis induced by the
      complexes was assayed by western blot analysis.

PMID- 28511065
TI  - Quantifying the brain's sheet structure with normalized convolution.
AB  - The hypothesis that brain pathways form 2D sheet-like structures layered in 3D as
      "pages of a book" has been a topic of debate in the recent literature. This
      hypothesis was mainly supported by a qualitative evaluation of "path
      neighborhoods" reconstructed with diffusion MRI (dMRI) tractography.
      Notwithstanding the potentially important implications of the sheet structure
      hypothesis for our understanding of brain structure and development, it is still
      considered controversial by many for lack of quantitative analysis. A means to
      quantify sheet structure is therefore necessary to reliably investigate its
      occurrence in the brain. Previous work has proposed the Lie bracket as a
      quantitative indicator of sheet structure, which could be computed by
      reconstructing path neighborhoods from the peak orientations of dMRI orientation
      density functions. Robust estimation of the Lie bracket, however, is challenging
      due to high noise levels and missing peak orientations. We propose a novel method
      to estimate the Lie bracket that does not involve the reconstruction of path
      neighborhoods with tractography. This method requires the computation of
      derivatives of the fiber peak orientations, for which we adopt an approach called
      normalized convolution. With simulations and experimental data we show that the
      new approach is more robust with respect to missing peaks and noise. We also
      demonstrate that the method is able to quantify to what extent sheet structure is
      supported for dMRI data of different species, acquired with different scanners,
      diffusion weightings, dMRI sampling schemes, and spatial resolutions. The
      proposed method can also be used with directional data derived from other
      techniques than dMRI, which will facilitate further validation of the existence
      of sheet structure.

PMID- 28511066
TI  - Deep image mining for diabetic retinopathy screening.
AB  - Deep learning is quickly becoming the leading methodology for medical image
      analysis. Given a large medical archive, where each image is associated with a
      diagnosis, efficient pathology detectors or classifiers can be trained with
      virtually no expert knowledge about the target pathologies. However, deep
      learning algorithms, including the popular ConvNets, are black boxes: little is
      known about the local patterns analyzed by ConvNets to make a decision at the
      image level. A solution is proposed in this paper to create heatmaps showing
      which pixels in images play a role in the image-level predictions. In other
      words, a ConvNet trained for image-level classification can be used to detect
      lesions as well. A generalization of the backpropagation method is proposed in
      order to train ConvNets that produce high-quality heatmaps. The proposed solution
      is applied to diabetic retinopathy (DR) screening in a dataset of almost 90,000
      fundus photographs from the 2015 Kaggle Diabetic Retinopathy competition and a
      private dataset of almost 110,000 photographs (e-ophtha). For the task of
      detecting referable DR, very good detection performance was achieved: Az=0.954 in
      Kaggle's dataset and Az=0.949 in e-ophtha. Performance was also evaluated at the
      image level and at the lesion level in the DiaretDB1 dataset, where four types of
      lesions are manually segmented: microaneurysms, hemorrhages, exudates and cotton
      wool spots. For the task of detecting images containing these four lesion types,
      the proposed detector, which was trained to detect referable DR, outperforms
      recent algorithms trained to detect those lesions specifically, with pixel-level
      supervision. At the lesion level, the proposed detector outperforms heatmap
      generation algorithms for ConvNets. This detector is part of the Messidor(r)
      system for mobile eye pathology screening. Because it does not rely on expert
      knowledge or manual segmentation for detecting relevant patterns, the proposed
      solution is a promising image mining tool, which has the potential to discover
      new biomarkers in images.

PMID- 28511069
TI  - Ischaemic preconditioning - Current knowledge and potential future applications
      after 30 years of experience.
AB  - Ischaemic preconditioning (IPC) phenomenon has been known for thirty years.
      During that time several studies showed that IPC provided by brief ischaemic and
      reperfusion episodes prior to longer ischaemia can bestow a protective effect to
      both preconditioned and also remote organs. IPC affecting remote organs is called
      remote ischaemic preconditioning. Initially, most IPC studies were focused on
      enhancing myocardial resistance to subsequent ischaemia and reperfusion injury.
      However, preconditioning was found to be a universal phenomenon and was observed
      in various organs and tissues including the heart, liver, brain, retina, kidney,
      skeletal muscles and intestine. Currently, there are a lot of simultaneous
      studies are underway aiming at finding out whether IPC can be helpful in
      protecting these organs. The mechanism of local and remote IPC is complex and not
      well known. Several triggers, intracellular pathways and effectors, humoral,
      neural and induced by genetic changes may be considered potential pathways in the
      protective activity of local and remote IPC. Local and remote IPC mechanism may
      potentially serve as heart protection during cardiac surgery and may limit the
      infarct size of the myocardium, can be a strategy for preventing the development
      of acute kidney injury development and liver damage during transplantation, may
      protect the brain against ischaemic injury. In addition, the method is safe, non
      invasive, cheap and easily applicable. The main purpose of this review article is
      to present new advances which would help to understand the potential mechanism of
      IPC. It also discusses both its potential applications and utility in clinical
      settings.

PMID- 28511067
TI  - A fuzzy logic-based tool to assess beef cattle ranching sustainability in complex
      environmental systems.
AB  - One of the most relevant issues in discussion worldwide nowadays is the concept
      of sustainability. However, sustainability assessment is a difficult task due to
      the complexity of factors involved in the natural world added to the human
      interference. In order to assess the sustainability of beef ranching in complex
      and uncertain tropical environment systems this paper describes a decision
      support system based on fuzzy rule-approach, the Sustainable Pantanal Ranch
      (SPR). This tool was built by a set of measurements and indicators integrated by
      fuzzy logic to evaluate the attributes of the three dimensions of sustainability.
      Indicators and decision rules, as well as scenario evaluations, were obtained
      from workshops involving multi-disciplinary team of experts. A Fuzzy Rule-Based
      System (FRBS) was developed to each attribute, dimension and general index. The
      essential parts of the FRBS are the knowledge database, rules and the inference
      engine. The FuzzyGen and WebFuzzy tools were developed to support the FRBS and
      both showed efficiency and low cost for digital applications. The results of each
      attribute, dimension and index were presented as radar graphs, showing the
      individual value (0-10) of each indicator. In the validation process using the
      WebFuzzy, different combinations of indicators were made for each attribute index
      to show the corresponding output, and which confirm the feasibility and usability
      of the tool.

PMID- 28511070
TI  - Impact of exaggerated blood pressure response in normotensive individuals on
      future hypertension and prognosis: Systematic review according to PRISMA
      guideline.
AB  - PURPOSE: Arterial hypertension (aHT) is the leading risk factor for morbidity and
      mortality worldwide. Blood pressure (BP) deviation at rest is well defined and
      accompanies risk for cardiovascular events and cardiovascular mortality. A
      growing body of evidence emphasises that an exaggerated blood pressure response
      (EBPR) in cardiopulmonary exercise testing (CPET) could help to identify
      seemingly cardiovascular healthy and normotensive subjects, who have an increased
      risk of developing aHT and cardiovascular events in the future. MATERIALS AND
      METHODS: The PubMed online database was searched for published studies reporting
      exercise-related BP and both the risk of aHT and cardiovascular events in the
      future. RESULTS: We identified 18 original studies about EBPR in CPET, which
      included a total of 35,151 normotensive individuals for prediction of new onset
      of aHT in the future and 11 original studies with 43,012 enrolled subjects with
      the endpoint of cardiovascular events in the future. Although an EBPR under CPET
      is not well defined, a large number of studies emphasise that EBPR in CPET is
      associated with both new-onset aHT and cardiovascular events in the future.
      CONCLUSIONS: A growing number of studies support the hypothesis that EBPR in CPET
      may be a diagnostic tool to identify subjects with an elevated risk of developing
      aHT and cardiovascular events in the future.

PMID- 28511068
TI  - Biotechnology and the transformation of vaccine innovation: The case of the
      hepatitis B vaccines 1968-2000.
AB  - The approval, from 1986, of a series of recombinant hepatitis B vaccines was a
      landmark both in the growth of biotechnology and in the development of the
      vaccine innovation system. In this paper, we show how the early development of
      the hepatitis B vaccines was shaped by a political and economic context that
      newly favoured commercialisation of academic research, including the
      appropriation and management of intellectual property; we elucidate the
      contingent interests and motivations that led new biotechnology companies and
      established pharmaceutical businesses to invest in developing recombinant
      vaccines specifically against hepatitis B; and we show how these and other
      factors combined to make those vaccines an unexpected commercial success.
      Broadening the scope of our analysis to include not just North America and Europe
      but also low- and middle-income countries, we show how the development of the
      hepatitis B vaccines facilitated the emergence of a two-tier innovation system
      structured by tensions between the demands for commercial profitability on the
      one hand, and the expectation of public health benefit for low- and middle-income
      countries on the other.

PMID- 28511071
TI  - Effects of gamma-radiation on cell growth, cell cycle and promoter methylation of
      22 cell cycle genes in the 1321NI astrocytoma cell line.
AB  - PURPOSE: DNA damage caused by radiation initiates biological responses affecting
      cell fate. DNA methylation regulates gene expression and modulates DNA damage
      pathways. Alterations in the methylation profiles of cell cycle regulating genes
      may control cell response to radiation. In this study we investigated the effect
      of ionizing radiation on the methylation levels of 22 cell cycle regulating genes
      in correlation with gene expression in 1321NI astrocytoma cell line. METHODS:
      1321NI cells were irradiated with 2, 5 or 10Gy doses then analyzed after 24, 48
      and 72h for cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazoliu bromide) assay. Flow cytometry were used to study the effect
      of 10Gy irradiation on cell cycle. EpiTect Methyl II PCR Array was used to
      identify differentially methylated genes in irradiated cells. Changes in gene
      expression was determined by qPCR. Azacytidine treatment was used to determine
      whether DNA methylation affectes gene expression. RESULTS: Our results showed
      that irradiation decreased cell viability and caused cell cycle arrest at G2/M.
      Out of 22 genes tested, only CCNF and RAD9A showed some increase in DNA
      methylation (3.59% and 3.62%, respectively) after 10Gy irradiation, and this
      increase coincided with downregulation of both genes (by 4 and 2 fold,
      respectively). TREATMENT: with azacytidine confirmed that expression of CCNF and
      RAD9A genes was regulated by methylation. CONCLUSIONS: 1321NI cell line is highly
      radioresistant and that irradiation of these cells with a 10Gy dose increases DNA
      methylation of CCNF and RAD9A genes. This dose down-regulates these genes,
      favoring G2/M arrest.

PMID- 28511072
TI  - Pro-inflammatory cytokines associated with clinical severity of dry eye disease
      of patients with depression.
AB  - PURPOSE: The aim of this study was to assess the correlation of inflammatory
      cytokines levels in tears with severity of dry eye disease in a cohort of
      patients with depression. MATERIAL AND METHODS: Tear fluid samples were collected
      from 32 patients with depression treated with antidepressants, and 34 healthy
      subjects. Cytokines were assessed by ELISA. All the subjects completed the Beck
      Depression Inventory and performed the ophthalmic examination, including dry eye
      tests. RESULTS: The tear fluid levels of IL-6, IL-17 and TNF-alpha in depressive
      patients were higher than in controls. The clinical severity of dry eye disease
      correlated significantly with the IL-17 and TNF-alpha levels. CONCLUSIONS: Our
      results suggest a crucial role of inflammatory cytokines, especially IL-17 and
      TNF-alpha, in the development of severe dry eye disease in patients with
      depression. Clarification of the role pro-inflammatory cytokines in the
      pathogenesis of ocular findings in depressive patients may be useful in
      establishing immunotherapeutic strategies for this disease.

PMID- 28511074
TI  - Charcot arthropathy of the knee after unsuccessful spinal stenosis surgery: A
      case report.
AB  - INTRODUCTION: Charcot arthropathy was first described in 1868 by Jean Martin
      Charcot as a progressive and destructive joint disease. Diabetes, polyneuropathy,
      syphilis, syrengomyelia and chronic alcoholism are the main causes of the
      disease. In this study we present a Charcot arthropathy of the knee seen after
      unsuccessful spinal stenosis surgery. PRESENTATION OF CASE: We report here a case
      of 62 years old patient with Charcot arthropathy at her left knee developed one
      year after spinal stenosis surgery. The patient's knee joint was already beyond
      the fragmentation and coalescence stages at the moment of physical examination.
      Patient had already been treated for Charcot foot four years before spinal
      surgery. Because of an unsuccessful spinal surgery, proximal migration of the
      level of the sensorineural loss negatively affected the polyneuropathy and
      eventually resulted in Charcot knee joint in a short period of time. DISCUSSION:
      However, the etiology of the neuropathic arthropathy hasn't been well described
      yet, it is usually seen at patients with diabetes mellitus as a long-term
      complication with or without polyneuropathy. In addition to the spinal canal
      pathologies, it is reported that Charcot arthropathy can be seen even after
      spinal anesthesia procedures. CONCLUSION: In conclusion, spinal procedures should
      be applied with extra caution on the patients with polyneuropathy or any
      neuropathic arthropathy. It should be remembered that it is possible to encounter
      unexpected complications such as proximally migration of the level of
      sensorineural loss and progression of the actual disease after spinal procedures
      of these patients.

PMID- 28511073
TI  - Preparation and evaluation of L- and D-5-[18F]fluorotryptophan as PET imaging
      probes for indoleamine and tryptophan 2,3-dioxygenases.
AB  - : Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases
      catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in
      kynurenine pathway. In the tumor microenvironment, their increased activity
      prevents normal immune function, i.e. tumor cell recognition and elimination by
      cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance
      the activity of cancer immunotherapeutics by reversing immune dysfunction. We
      sought to investigate the properties of radiolabeled 5-[18F]fluorotryptophan with
      respect to its ability for measuring IDO1 and TDO2 activity by positron emission
      tomography (PET). RESULTS: L-5-[18F]fluorotryptophan and D-5
      [18F]fluorotryptophan were synthesized by Cu(I) catalyzed
      [18F]fluorodeboronylation of Boc/tBu protected precursors in moderate yields
      (1.5+/-0.6%) sufficient for pre-clinical studies. The specific activity of the
      product was 407-740GBq/MUmol, radiochemical purity >99% and enantiomeric excess
      90-99%. Enzymatic assay confirmed that L-5-fluorotryptophan is an IDO1 and TDO2
      substrate whereas the D-isomer is not. In-vitro cell uptake experiments using
      CT26 cells with doxycycline-induced overexpression of human-IDO1 and human-TDO2
      revealed an elevated cell uptake of L-5-[18F]fluorotryptophan upon induction of
      IDO1 or TDO2 enzymes compared to baseline; however, the uptake was observed only
      in the presence of low L-tryptophan levels in media. PET imaging experiments
      performed using tumor bearing mouse models expressing IDO1 at various levels
      (CT26, CT26-hIDO1, 17082A, 17095A) showed tumor uptake of the tracer elevated up
      to 8%ID/g; however, the observed tumor uptake could not be attributed to IDO1
      activity in the tumor tissue. The metabolism of L- and D- isomers was markedly
      different in vivo, the D-isomer was excreted by a combination of hepatobiliary
      and renal routes, the L-isomer underwent extensive metabolism to [18F]fluoride.
      CONCLUSION: The observed in vivo tumor uptake of the tracer could not be
      attributed to IDO1 or TDO2 enzyme activity in the tumor, presumably due to
      competition with endogenous tryptophan as well as rapid tracer metabolism.

PMID- 28511075
TI  - Using endoscopy to minimize the extent of resection in the management of giant
      GISTs of the stomach.
AB  - INTRODUCTION: The stomach is the most common site for GISTs. Wide local resection
      to achieve negative margins is the standard of care. Giants GISTs requiring
      extensive resection are usually managed with neo-adjuvant therapy followed by
      partial or total gastrectomy. PRESENTATION OF CASE: We present a case report of a
      giant GIST on the lesser curvature of the stomach. Neo-adjuvant therapy was
      administered. Intra-operative endoscopy was used to reduce the extent of gastric
      resection. DISCUSSION: Simultaneous intra-operative endoscopy demonstrated a 2mm
      fistula on the lesser curvature of the stomach. A stapler was used to encompass
      the mass and the fistulous opening. A frozen-section showed clear margins and the
      endoscope was used to perform an air-leak test. The patient recovered without
      complications. CONCLUSION: Intra-operative endoscopy can reduce the extent of
      gastric resection for large GISTs while maintaining the oncologic principles of
      negative margins and minimal tissue handling.

PMID- 28511076
TI  - The tissue distribution, metabolism and hepatotoxicity of benzoylurea pesticides
      in male Eremias argus after a single oral administration.
AB  - Benzoylurea pesticides (BPUs) are widely used to control the locust, but the
      toxicokinetics and hepatotoxicity of BPUs in lizards have not been investigated.
      In this study, the tissue distribution, metabolism and liver toxicity of
      diflubenzuron and flufenoxuron were assessed in the Eremias argus following a
      single oral exposure. Diflubenzuron preferred to accumulate in the fat and brain
      (>1.0 mg kg-1) and was rapidly eliminate in other tissues. In the liver, 4
      chloroaniline was one of diflubenzuron metabolites, although with a concentration
      less than 0.05% of the accumulated diflubenzuron. No significant difference was
      observed in the liver histopathology between the control and diflubenzuron
      exposure group. The expressions of Cyp1a and Ahr gene which control the cell
      apoptosis were also equal to the control level. After flufenoxuron exposure,
      biomodal phenomenon was observed in the liver, skin, brain, gonad, kidney, heart
      and blood circulation was an important route for the flufenoxuron penetration.
      The concentrations of flufenoxuron in all tissues were greater than 1.0 mg kg-1
      at 168 h. The excretion of flufenoxuron in the faeces was 1.5 fold higher than
      diflubenzuron. The hepatocytes in the flufenoxuron treated group showed
      vacuolation of cytoplasm and decreased nucleus. In addition, the Cyp1a and Ahr
      genes were significantly up-regulated in the flufenoxuron exposure group. These
      results suggested that the higher hepatotoxicity of flufenoxuron may be
      attributed to the higher residual level in the lizard tissues and the Cyp1a and
      Ahr genes can serve as biomarkers to assess the liver toxicity.

PMID- 28511077
TI  - Clinical and laboratory parameters predicting a requirement for the reevaluation
      of growth hormone status during growth hormone treatment: Retesting early in the
      course of GH treatment.
AB  - OBJECTIVE: We aimed to define the predictive criteria, in the form of specific
      clinical, hormonal and radiological parameters, for children with growth hormone
      deficiency (GHD) who may benefit from the reevaluation of GH status early in the
      course of growth hormone (GH) treatment. DESIGN AND METHODS: Two hundred sixty
      five children with growth hormone deficiency were retested by GH stimulation at
      the end of the first year of GH treatment. The initial clinical and laboratory
      characteristics of those with a normal (GH>=10ng/ml) response and those with a
      subnormal (GH<10ng/ml) response were compared to predict a normal GH status
      during reassessment. RESULTS: Sixty-nine patients (40.6%) out of the 170 patients
      with isolated growth hormone deficiency (IGHD) had a peak GH of >=10ng/ml during
      the retest. None of the patients with multiple pituitary hormone deficiency
      (MPHD) had a peak GH of >=10ng/ml. Puberty and sex steroid priming in
      peripubertal cases increased the probability of a normal GH response. Only one
      patient with IGHD who had an ectopic posterior pituitary without stalk
      interruption on MRI analysis showed a normal GH response during the retest.
      Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of >=9years or
      a height gain below 0.61 SDS during the first year of treatment had an increased
      probability of having a normal GH response at the retest. CONCLUSION: Early
      reassessment of GH status during GH treatment is unnecessary in patients who have
      MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year
      of therapy is recommended for patients with IGHD who have a height gain of <0.61
      SDS in the first year of treatment, especially those with a normal or
      'hypoplastic' pituitary on imaging. Priming can increase the likelihood of a
      normal response in patients in the pubertal age group who do not show overt signs
      of pubertal development.

PMID- 28511078
TI  - Performance of electro-osmotic dewatering on different types of sewage sludge.
AB  - The feasibility of pressure-driven electro-dewatering (EDW) on sludge samples
      taken after different biological processes, stabilisation methods or mechanical
      dewatering techniques was assessed. First, the influence of potential values on
      EDW of anaerobically and aerobically stabilised, mechanically dewatered, sludge
      samples was investigated. Preliminary tests carried out by applying a constant
      potential (10, 15 and 20V) in a lab-scale device confirmed the possibility to
      reach a dry solid (DS) content of up to 42.9%, which corresponds to an increase
      of 15% of the dry content in dewatered sludge without the application of the
      electrical field. Dewatering increased with the applied potential but at the
      expense of a higher energy consumption. A potential equal to 15V was chosen as
      the best compromise for EDW performance, in terms of DS content and energy
      consumption. Then, the influence of the mechanical dewatering was studied on
      aerobically stabilised sludge samples with a lower initial DS content: the higher
      initial water content led to a lower final DS content but with a considerable
      reduction of energy consumption. Finally, the biological process, studied by
      comparing sludge samples from conventional activated sludge and membrane
      bioreactor processes, didn't evidence any influence on EDW. Experimental results
      shown that DS obtained after mechanical dewatering, volatile solids and
      conductivity are the main factors influencing EDW. Anaerobically digested sludge
      reached the highest DS content, thanks to lower organic fraction.

PMID- 28511079
TI  - Psychosocial stress and obesity among children residing in Kaunas City.
AB  - INTRODUCTION: An unfavorable psychosocial environment has been associated with an
      increased prevalence of obesity among children. However, the available evidence
      on the association of low socioeconomic status and parent-child relationships
      with childhood obesity is scarce. The aim of our study was to conduct a
      simultaneous evaluation of the risks associated with pathological mother-child
      relationships, education level, and overweight/obesity among 4-6 year-old
      children. METHODS: This cross-sectional study included 1489 mother-child pairs
      living in Kaunas city, Lithuania. The Parenting Stress Index was measured using
      the Parent-Child Dysfunctional Interaction subscale. Children's
      overweight/obesity was defined as the body mass index >=18kg/m2. Logistic
      regression models as well as crude and adjusted odds ratios (OR) and their 95%
      confidence intervals (CI) were used to indicate the strength of the associations
      between childhood overweight/obesity, maternal education level, and psychosocial
      stress. RESULTS: The percentage of children with overweight/obesity rose with an
      increasing Parenting Stress Index score. The percentage of children with
      overweight/obesity in the group of parents with better education and normal
      mother-child relations was 6.0%, while in the group of less educated parents and
      pathological mother-child relations, this percentage reached 13.9%. The
      stratified multivariable model showed that, with reference to the group of better
      educated parents and normal mother-child relations, lower education level and
      pathological mother-child relations were statistically significant risk factors
      for overweight/obesity in 4-6 year-old children, increasing the OR of
      overweight/obesity (aOR: 2.43; 95% CI: 1.31-4.51). Pathological mother-child
      relations and maternal smoking mediated the effect of low maternal education
      level on children's BMI z-scores. CONCLUSION: Pathological mother-child
      relations, lower parental education levels, and smoking may be predictors of
      children's overweight/obesity. Measures oriented towards health behavior and
      psychosocial stress management should be encouraged among parents in order to
      decrease the risk of overweight/obesity in their children.

PMID- 28511081
TI  - A novel ultrasonic surface machining tool utilizing elastic traveling waves.
AB  - With the rapid development of modern industrial technology and high performance
      technology products, ultra-precision machining technology becomes increasingly
      important. However, joint clearance of kinematic pairs, lack of feeding accuracy
      and overlarge contact stress still limit the further improvement of ultra
      precision machining technology. In this study, a novel surface machining method
      utilizing structural elastic waves was proposed, and a machining tool using the
      piezoelectric actuating principle was presented for verifying the proposed
      method. Two vibration modes with a phase shift of pi/2 in both space and time
      domains are exited simultaneously in the elliptical motion of points on the
      structural surface. By means of adjusting driving signal parameters, such as
      frequency, voltage amplitude and phase shift, different machining performances
      could be achieved. The configuration and working vibration modes of the proposed
      machining tool were firstly calculated by the finite element method, and then the
      optimal working frequency of the machining tool prototype was determined by
      vibration characteristic experiments. At last, machining characteristic
      experiments were conducted to validate the proposed machining method.
      Experimental results showed that the minimum working contact force between the
      machining tool and workpiece was 1N, and the chipped depth of 1.93MUm was
      achieved at the same contact force after machining for 5min. And at the
      conditions of the contact force of 6N, two driving voltages of 400Vpp with a
      phase shift of pi/2, and machining time of 5min, the prototype could achieve to
      machine the workpiece most efficiently and the roughness of the machined
      workpiece surface could be reached approximating 0.20MUm. In conclusion, this
      proposed machining method could achieve a good quality machined surface with low
      residual stress and little damage by applying low contact force. Furthermore, it
      also had the advantage of no joint clearance error due to no kinematic pair in
      the structure, which improves the machining precision.

PMID- 28511082
TI  - Nonlinear Lamb waves for fatigue damage identification in FRP-reinforced steel
      plates.
AB  - A nonlinear Lamb-wave-based method for fatigue crack detection in steel plates
      with and without carbon fibre reinforcement polymer (CFRP) reinforcement is
      presented in this study. Both numerical simulation and experimental evaluation
      were performed for Lamb wave propagation and its interaction with a fatigue crack
      on these two steel plate types. With the generation of the second harmonic, the
      damage-induced wave nonlinearities were identified by surface-bonded
      piezoelectric sensors. Numerical simulation revealed that the damage-induced wave
      component at the second harmonic was slightly affected by the existence of CFRP
      laminate, although the total wave energy was decreased because of wave leakage
      into the CFRP laminate. Due to unavoidable nonlinearity from the experimental
      environments, it was impractical to directly extract the time-of-flight of the
      second harmonic for locating the crack. To this end, the correlation coefficient
      of benchmark and signal with damage at double frequency in the time domain was
      calculated, based on which an imaging method was introduced to locate the fatigue
      crack in steel plates with and without CFRP laminates.

PMID- 28511080
TI  - Cadmium and Alzheimer's disease mortality in U.S. adults: Updated evidence with a
      urinary biomarker and extended follow-up time.
AB  - Cadmium has been linked to impaired cognitive function in adults and may cause
      behavioral, physiological and molecular abnormalities characteristic of
      Alzheimer's disease (AD) in animals. Evidence linking cadmium and AD in humans is
      limited, but supportive. In the most recent epidemiologic study, blood cadmium in
      U.S. adults was positively associated with elevated AD mortality 7-13 years
      later. The association between urinary cadmium - an arguably more appropriate
      biomarker for studying chronic diseases - and AD mortality has not yet been
      explored. Further study of cadmium and AD mortality in an independent population,
      with longer follow-up, and stratified by sex is also needed. We sought to answer
      these questions using the U.S. National Health and Nutrition Examination Survey
      (NHANES) (1999-2006 cycles) and NHANES III (interviews in 1988-1994) datasets,
      separately linked to AD mortality as of 2011. We used survey-weighted Cox
      regression models predicting age at AD death and adjusted for race/ethnicity,
      sex, smoking status, education and urinary creatinine. An interquartile range
      (IQR; IQR=0.51ng/mL) increase in urinary cadmium was associated with 58% higher
      rate of AD mortality (hazard ratio (HR)=1.58, 95% CI: 1.20, 2.09. p-value=0.0009,
      mean follow-up: 7.5 years) in NHANES 1999-2006 participants. In contrast, in
      NHANES III participants, an IQR (IQR=0.78ng/mL) increase in urinary cadmium was
      not associated with AD mortality (HR=0.85, 95% CI: 0.63, 1.17, p-value=0.31, mean
      follow-up: 13 years). Also in the NHANES III sample however, when the maximum
      follow-up time was restricted to 12.7 years (i.e. the same as NHANES 1999-2006
      participants) and urinary creatinine adjustments were not made, urinary cadmium
      was associated with elevated AD mortality (HR=1.11, 95% CI: 1.02, 1.20, p
      value=0.0086). Our study partially supported an association between cadmium and
      AD mortality, but the sensitivity of results to follow-up time and creatinine
      adjustments necessitate cautious interpretation of the association. Further
      studies, particularly those on toxicological mechanisms, are required to fully
      understand the nature of the "cadmium-AD mortality" association.

PMID- 28511084
TI  - Examining ethnic inequalities in health and tenure in England: A repeated cross
      sectional analysis.
AB  - Ethnic minorities experience multiple inequalities across different domains
      including health and tenure. Notwithstanding extensive research demonstrating a
      clear connection between tenure and health, the relationship between health,
      tenure and ethnicity is under-explored. In this paper, we examine ethnic
      inequalities in health and tenure in England using cross-sectional census
      microdata for 1991, 2001 and 2011. We find that ethnic inequalities in health
      persist over time while the relationship between health and tenure varies between
      ethnic groups. These results suggest that traditional explanations linking health
      and tenure are not sufficient to adequately capture the myriad experiences of
      different ethnic groups.

PMID- 28511083
TI  - How do type and size of natural environments relate to physical activity
      behavior?
AB  - Natural environments (NE) are promoted as places that support physical activity
      (PA), but evidence on PA distribution across various types and sizes of NE is
      lacking. Accelerometers and GPS-devices measured PA of Dutch general population
      adults aged 45-65 years (N=279). Five NE types were distinguished: 'parks',
      'recreational area', 'agricultural green', 'forest & moorland', and 'blue space',
      and four categories of size: 0-3, 3-7, 7-27, and >=27 ha. Modality (i.e.
      spatially concentrated PA, walking, jogging, and cycling) and intensity (i.e.
      sedentary behavior, LPA, and MVPA) of PA varied significantly between NE types.
      Compared to parks, less sedentary behavior and walking but more spatially
      concentrated PA was observed in recreational areas and green space. Cycling
      levels were found to be significantly lower in recreational areas and forest &
      moorland, but higher in blue space as compared to parks. Larger sized NE (>=7 ha)
      were associated with higher levels of MVPA, walking, jogging and cycling. Insight
      in which environments (according to type and size) facilitate PA, contributes to
      the development of tailored PA promoting interventions with ensuing implications
      for public health.

PMID- 28511085
TI  - Development, implementation, and effects of an integrated web-based teaching
      model in a nursing ethics course.
AB  - BACKGROUND: Ethical competence, which is reflected in the ability to detect
      ethical challenges in clinical situations and engage in deliberate thinking on
      ethical actions, is one of the core competencies of nursing practice. PURPOSE:
      The purpose of this study was to develop and implement an interactive situational
      e-learning system, integrating nursing ethical decisions into a nursing ethics
      course, and to evaluate the effects of this course on student nurses' ethical
      decision-making competence. PROJECT DESIGN: The project was designed to be
      carried out in two phases. In the first phase, an interactive situated e-learning
      system was developed and integrated into the nursing ethics course. The second
      phase involved implementing the course and evaluating its effects in a quasi
      experimental study. The course intervention was designed for 2h per week over one
      semester (18weeks). PARTICIPANTS: A total of 100 two-year technical college
      nursing students in their second year of the program participated in the study,
      with 51 in the experimental group and 49 in the control group. RESULTS: After
      completing the course, the students in the experimental group showed significant
      improvement in nursing ethical decision-making competence, including skills in
      "raising questions," "recognizing differences," "comparing differences," "self
      dialogue," "taking action," and "identifying the implications of decisions made,"
      compared to their performance prior to the class. After controlling for factors
      influencing learning effects, students in the experimental group showed
      superiority to those in the control group in the competency of "recognizing
      differences." The students in the experimental group reported that the course
      pushed them to search for and collect information needed to resolve the ethical
      dilemma. CONCLUSIONS: The interactive situational e-learning system developed by
      our project was helpful in developing the students' competence in ethical
      reasoning. The e-learning system and the situational teaching materials used in
      this study may be applicable in nursing and related professional ethics courses.

PMID- 28511086
TI  - Local endometrial injury in women with failed IVF undergoing a repeat cycle: A
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of local endometrial injury in women
      undergoing in vitro fertilization (IVF) with at least one previous unsuccessful
      attempt. STUDY DESIGN: Randomized controlled trial. Recruited women were
      randomized into two groups. In group A (pipelle group), women underwent pipelle
      biopsy twice in the luteal phase in the cycle prior to IVF. In group B (control),
      women did not undergo any intervention prior to IVF. The primary outcome was
      clinical pregnancy rate. The secondary outcomes included live birth, miscarriage,
      multiple pregnancy and preterm delivery rates. RESULTS: One hundred and eleven
      women were included in the study with 55 in the pipelle group and 56 in the
      control arm. The baseline clinical characteristics were similar in both groups.
      The clinical pregnancy rates were not significantly different between pipelle and
      control group (34.09% vs. 27.65%; Odds ratio, OR 1.35, 95% confidence interval,
      CI 0.55-3.30). The live birth (31.81% vs. 25.53%; OR 1.36, 95% CI 0.55-3.39),
      multiple pregnancy (33.33% vs. 61.54%; OR 0.31, 95% CI 0.07-1.47), miscarriage
      (6.66% vs. 7.69%; OR 0.86, 95% CI 0.05-15.23) and preterm delivery rates (35.71%
      vs. 66.66%; OR 0.28, 95% CI 0.05-1.4) were also not significantly different
      between the two groups. CONCLUSION: Current study did not find any improvement in
      IVF success rates following endometrial injury in woman undergoing IVF after
      previous failed attempt.

PMID- 28511087
TI  - Optional use of CAM photosynthesis in two C4 species, Portulaca cyclophylla and
      Portulaca digyna.
AB  - Low levels of crassulacean acid metabolism (CAM) are demonstrated in two species
      with C4 photosynthesis, Portulaca cyclophylla and P. digyna. The expression of
      CAM in P. cyclophylla and P. digyna is facultative, i.e. optional. Well-watered
      plants did not accumulate acid at night and exhibited gas-exchange patterns
      consistent with C4 photosynthesis. CAM-type nocturnal acidification was
      reversible in that it was induced following drought and lost when droughted
      plants were rewatered. In P. cyclophylla, droughting was accompanied by a small
      but discernible net uptake of CO2 during the dark, whereas in P. digyna, net CO2
      exchange at night approached the CO2 compensation point but did not transition
      beyond it. This report brings the number of known C4 species with a capacity for
      expressing CAM to six. All are species of Portulaca. The observation of CAM in P.
      cyclophylla and P. digyna is the first for species in the opposite-leaved (OL)
      Portulacelloid-anatomy lineage of Portulaca and for the Australian clade therein.
      The other four species are within the alternate-leaved (AL) lineage, in the
      Atriploid-anatomy Oleracea and the Pilosoid-anatomy Pilosa clades. Studies of the
      evolutionary origins of C4 and CAM in Portulaca will benefit from a more wide
      range survey of CAM across its species, particularly in the C3-C4 intermediate
      containing Cryptopetala clade.

PMID- 28511088
TI  - Effects of increasing dietary organic selenium levels on meat fatty acid
      composition and oxidative stability in growing rabbits.
AB  - The effects of dietary organic selenium (Se) addition at 0.1, 0.5 and 2.5mg/kg
      vs. an unsupplemented basal diet (BD) on performance, fatty acid (FA) composition
      and oxidative stability were studied in muscle tissue of growing rabbits. Muscle
      Se content increased (P<0.001) in a dose dependent manner with dietary Se
      inclusion. Saturated FA (SFA) were affected linearly (P<0.05) and quadratically
      (P<0.05) by dietary Se addition. Polyunsaturated FA (PUFA) increased linearly
      (P<0.01) resulting in a linear increase in the PUFA:SFA ratio (P<0.01) with
      dietary Se increment. Feeding 0.5mgSe/kg diet reduced malondialdehyde (MDA) and
      oxygen radical absorbance capacity (ORAC) values in the muscle, whilst 2.5mgSe/kg
      diet increased MDA concentrations and tended to increase ORAC values, likely
      indicating oxidative stress. In conclusion, dietary Se supplementation at
      0.5mg/kg improves meat FA composition and oxidative stability, whereas at
      2.5mg/kg may induce pro-oxidant effects.

PMID- 28511089
TI  - A computational assessment of representative sampling of soil gas using existing
      groundwater monitoring wells screened across the water table.
AB  - Representative sampling is of great importance to decision making regarding
      contaminant site risks and remedial effectiveness. A focus here is whether
      existing groundwater monitoring wells screened across the water table can be
      sampled to yield representative indicators of soil gas composition. For the first
      time, we provide multi-phase, multi-component computational simulations to
      address this. We simulated high and low gas extractions rate strategies to sample
      the gas phase over short and extended screening intervals across the water table.
      We investigated the options against a field data set representative of typical
      hydrocarbon vapour profiles, inclusive of major gases, oxygen and carbon dioxide.
      We also evaluated the sampling options for uniform and non-uniform multi
      component gasoline LNAPL distributions, including hazardous chemicals. Less
      sensitivity to the sampling option was observed for depth-wise increasing
      concentration profiles with a near-constant concentration across the screen.
      Significant discrepancy between the ratio of different compounds in the sample
      and in-situ (real) values was observed for high-rate gas extraction (particularly
      for an extended-screen). Low-rate gas extraction provided satisfactory results
      for all the scenarios. Shorter screening slightly improved the accuracy of this
      option. Graphical representations are provided to allow assessment of the
      applicability of each sampling option for various site conditions.

PMID- 28511090
TI  - Inactivation of the KSRP gene modifies collagen antibody induced arthritis.
AB  - The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein,
      which negatively regulates the stability and/or translatability of many mRNA
      species encoding immune-relevant proteins. As KSRP is expressed in immune cells
      including T and B cells, neutrophils, macrophages and dendritic cells, we wanted
      to analyze its importance for the development of autoimmune diseases. We chose
      collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease
      mouse model in which neutrophils and macrophages constitute the main effector
      cell populations. We compared arthritis induction in wild type (WT) and KSRP-/-
      mice and paws were taken for histological sections and qPCR analysis.
      Furthermore, we determined the frequencies of spleen immune cells by flow
      cytometry. Cytokine levels in spleen cell supernatants were determined by
      cytometric bead array analyses (CBA). After CAIA induction we unexpectedly
      observed in WT animals much stronger swelling of the paws than in KSRP-/- mice.
      In accordance, histological staining of paw sections of KSRP-/- animals revealed
      much lower frequencies of infiltrating immune cells in the joints compared to WT
      animals. Furthermore, CAIA-treatment resulted in reduced expression of several
      inflammatory factors (like CXCL-1, iNOS, TNF-alpha and S100A8) as well as immune
      cell marker genes (e.g. LFA-1, CD68, Ly6G) in the joints of KSRP-/- mice. Spleen
      cells of KSRP-/- mice showed lower frequencies of myeloid cells. On cytokine
      level IFN-gamma production was increased in spleen cells of KSRP-/- mice compared
      to WT samples. These data surprisingly suggest that the absence of KSRP protects
      against the induction of inflammatory arthritis.

PMID- 28511091
TI  - Molecular cloning and characterization of DNGR-1 in rhesus macaques.
AB  - DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain
      family 9 member A (CLEC9A), is a promising target for immunological therapeutics
      and vaccination against tumors and viruses. However, little is known about its
      property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA,
      and found that its coding region could encode a 241-amino acid polypeptide with
      91.7% sequence identity and similar antigenicity to that of humans. Both free and
      cell surface rhesus macaque DNGR-1 expressed in vitro could bind to
      apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to
      pyroptotic cells stimulated with PMA and LPS. We also demonstrated that rhesus
      macaque DNGR-1 mRNA was present in all the examined tissues, with the highest in
      lymph nodes, spleen, blood, and thymus. The expression of DNGR-1 that is highly
      similar to that of humans warranted the usefulness of rhesus macaques in testing
      human therapeutics and vaccines targeting DNGR-1, especially those for HIV/AIDS.

PMID- 28511092
TI  - Epigenetics and immunotherapy: The current state of play.
AB  - Cancer cells employ a number of mechanisms to escape immunosurveillance and
      facilitate tumour progression. The recent explosion of interest in immunotherapy,
      especially immune checkpoint blockade, is a result of discoveries about the
      fundamental ligand-receptor interactions that occur between immune and cancer
      cells within the tumour microenvironment. Distinct ligands expressed by cancer
      cells engage with cell surface receptors on immune cells, triggering inhibitory
      pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant.
      Importantly, recent studies on the role of epigenetics in immune evasion have
      exposed a key role for epigenetic modulators in augmenting the tumour
      microenvironment and restoring immune recognition and immunogenicity. Epigenetic
      drugs such as DNA methyltransferase and histone deacetylase inhibitors can
      reverse immune suppression via several mechanisms such as enhancing expression of
      tumour-associated antigens, components of the antigen processing and presenting
      machinery pathways, immune checkpoint inhibitors, chemokines, and other immune
      related genes. These discoveries have established a highly promising basis for
      studies using combined epigenetic and immunotherapeutic agents as anti-cancer
      therapies. In this review, we discuss the exciting role of epigenetic
      immunomodulation in tumour immune escape, emphasising its significance in priming
      and sensitising the host immune system to immunotherapies through mechanisms such
      as the activation of the viral defence pathway. With this background in mind, we
      highlight the promise of combined epigenetic therapy and immunotherapy, focusing
      on immune checkpoint blockade, to improve outcomes for patients with many
      different cancer types.

PMID- 28511093
TI  - Hypoxia-based strategies for regenerative dentistry-Views from the different
      dental fields.
AB  - The understanding of the cell biological processes underlying development and
      regeneration of oral tissues leads to novel regenerative approaches. Over the
      past years, knowledge on key roles of the hypoxia-based response has become more
      profound. Based on these findings, novel regenerative approaches for dentistry
      are emerging, which target cellular oxygen sensors. These approaches include
      hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in
      studies on hypoxia and hypoxia-based strategies in regenerative dentistry
      highlights the growing attention to hypoxia's role in regeneration and its
      underlying biology, as well as its application in a therapeutic setting. In this
      narrative review, we present the current knowledge on the role of hypoxia in oral
      tissues and review the proposed hypoxia-based approaches in different fields of
      dentistry, including endodontics, orthodontics, periodontics, and oral surgery.

PMID- 28511094
TI  - Isolation and genetic analysis of pure cells from forensic biological mixtures:
      The precision of a digital approach.
AB  - Latest genotyping technologies allow to achieve a reliable genetic profile for
      the offender identification even from extremely minute biological evidence. The
      ultimate challenge occurs when genetic profiles need to be retrieved from a
      mixture, which is composed of biological material from two or more individuals.
      In this case, DNA profiling will often result in a complex genetic profile, which
      is then subject matter for statistical analysis. In principle, when more
      individuals contribute to a mixture with different biological fluids, their
      single genetic profiles can be obtained by separating the distinct cell types
      (e.g. epithelial cells, blood cells, sperm), prior to genotyping. Different
      approaches have been investigated for this purpose, such as fluorescent-activated
      cell sorting (FACS) or laser capture microdissection (LCM), but currently none of
      these methods can guarantee the complete separation of different type of cells
      present in a mixture. In other fields of application, such as oncology,
      DEPArrayTM technology, an image-based, microfluidic digital sorter, has been
      widely proven to enable the separation of pure cells, with single-cell precision.
      This study investigates the applicability of DEPArrayTM technology to forensic
      samples analysis, focusing on the resolution of the forensic mixture problem. For
      the first time, we report here the development of an application-specific
      DEPArrayTM workflow enabling the detection and recovery of pure homogeneous cell
      pools from simulated blood/saliva and semen/saliva mixtures, providing full
      genetic match with genetic profiles of corresponding donors. In addition, we
      assess the performance of standard forensic methods for DNA quantitation and
      genotyping on low-count, DEPArrayTM-isolated cells, showing that pure, almost
      complete profiles can be obtained from as few as ten haploid cells. Finally, we
      explore the applicability in real casework samples, demonstrating that the
      described approach provides complete separation of cells with outstanding
      precision. In all examined cases, DEPArrayTM technology proves to be a
      groundbreaking technology for the resolution of forensic biological mixtures,
      through the precise isolation of pure cells for an incontrovertible attribution
      of the obtained genetic profiles.

PMID- 28511095
TI  - Independent validation of DNA-based approaches for age prediction in blood.
AB  - Numerous molecular biomarkers have been proposed as predictors of chronological
      age. Among them, T-cell specific DNA rearrangement and DNA methylation markers
      have been introduced as forensic age predictors in blood because of their high
      prediction accuracy. These markers appear highly promising, but for better
      application to forensic casework sample analysis the proposed markers and
      genotyping methods must be tested further. In the current study, signal-joint T
      cell receptor excision circles (sjTRECs) and DNA methylation markers located in
      the ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 genes were reanalyzed in 100 Korean
      blood samples to test their associations with chronological age, using the same
      analysis platform used in previous reports. Our study replicated the age
      association test for sjTREC and DNA methylation markers in the 5 genes in an
      independent validation set of 100 Koreans, and proved that the age predictive
      performance of the previous models is relatively consistent across different
      population groups. However, the extent of age association at certain CpG loci was
      not identical in the Korean and Polish populations; therefore, several age
      predictive models were retrained with the data obtained here. All of the 3 models
      retrained with DNA methylation and/or sjTREC data have a CpG site each from the
      ELOVL2 and FHL2 genes in common, and produced better prediction accuracy than
      previously reported models. This is attributable to the fact that the retrained
      model better fits the existing data and that the calculated prediction accuracy
      could be higher when the training data and the test data are the same. However,
      it is notable that the combination of different types of markers, i.e., sjTREC
      and DNA methylation, improved prediction accuracy in the eldest group. Our study
      demonstrates the usefulness of the proposed markers and the genotyping method in
      an independent dataset, and suggests the possibility of combining different types
      of DNA markers to improve prediction accuracy.

PMID- 28511096
TI  - Improved amplification results following episodes of failure to amplify at the
      Amelogenin Locus using PowerPlex(r) ESI 16 Fast System.
AB  - In 2012 the Israel Police DNA Casework laboratory adopted the 16 STR PowerPlex(r)
      ESI kit for routine use. The Promega Company updated this kit and developed the
      PowerPlex(r) ESI 16 Fast System in which all autosomal primer pairs remained
      identical to the original set, except at the amelogenin site. The master mix was
      improved and optimized which allowed for direct, faster and more robust
      amplification. Prior to implementing the PowerPlex(r) ESI 16 Fast System in our
      lab, we conducted a preliminary assay where 213 casework samples were amplified
      using the new kit. These samples had previously been extracted by one of two
      extraction kits employed by our lab. (the PrepFiler ExpressTM and PrepFiler BTATM
      Forensic DNA Extraction Kits). The amplification results from these samples were
      compared to samples amplified using the original PowerPlex(r) ESI 16 kit.
      Multiple incidents of failure to amplify at the amelogenin locus were noted using
      the new system with the recommended protocol at a rate of 13% (28 of 213
      samples). Experiments were performed to understand whether these amplification
      failures could be a result of primer binding site mutations, extraction method
      reagents and/or inhibitors. The conclusions reached following these experiments,
      in conjunction with consultation with the manufacturer, led to the trial of a
      modified amplification protocol where the suggested annealing temperature was
      reduced by 2 degrees. To evaluate the efficiency of this altered protocol, a
      comparison study was undertaken where 88 additional casework samples were chosen
      and amplified using both the modified 58 degrees C and the recommended 60 degrees
      C annealing temperatures. We concluded that the most effective method in our
      laboratory for achieving a consistent and balanced amplification at the
      amelogenin locus was to reduce the annealing temperature from the manufacturer's
      recommended 60 degrees C to 58 degrees C. This modification resulted in a
      reduction of the failure to amplify at the amelogenin locus from 13% (28/213) to
      1.1% (1/88) without any observed changes to the autosomal STR amplification
      results.

PMID- 28511097
TI  - The relationship between social desirability bias and self-reports of health,
      substance use, and social network factors among urban substance users in
      Baltimore, Maryland.
AB  - BACKGROUND: Social desirability response bias may lead to inaccurate self-reports
      and erroneous study conclusions. The present study examined the relationship
      between social desirability response bias and self-reports of mental health,
      substance use, and social network factors among a community sample of inner-city
      substance users. METHODS: The study was conducted in a sample of 591 opiate and
      cocaine users in Baltimore, Maryland from 2009 to 2013. Modified items from the
      Marlowe-Crowne Social Desirability Scale were included in the survey, which was
      conducted face-to-face and using Audio Computer Self Administering Interview
      (ACASI) methods. RESULTS: There were highly statistically significant differences
      in levels of social desirability response bias by levels of depressive symptoms,
      drug use stigma, physical health status, recent opiate and cocaine use, Alcohol
      Use Disorders Identification Test (AUDIT) scores, and size of social networks.
      There were no associations between health service utilization measures and social
      desirability bias. In multiple logistic regression models, even after including
      the Center for Epidemiologic Studies Depression Scale (CES-D) as a measure of
      depressive symptomology, social desirability bias was associated with recent drug
      use and drug user stigma. Social desirability bias was not associated with
      enrollment in prior research studies. CONCLUSIONS: These findings suggest that
      social desirability bias is associated with key health measures and that the
      associations are not primarily due to depressive symptoms. Methods are needed to
      reduce social desirability bias. Such methods may include the wording and
      prefacing of questions, clearly defining the role of "study participant," and
      assessing and addressing motivations for socially desirable responses.

PMID- 28511098
TI  - E-cigarette liquids: Constancy of content across batches and accuracy of
      labeling.
AB  - AIMS: To assess whether bottles of refill liquids for e-cigarettes were filled
      true to label, whether their content was constant across two production batches,
      and whether they contained impurities. METHODS: In 2013, we purchased on the
      Internet 18 models from 11 brands of e-liquids. We purchased a second sample of
      the same models 4months later. We analyzed their content in nicotine, anabasine,
      propylene glycol, glycerol, ethylene glycol and diethylene glycol, and tested
      their pH. RESULTS: The median difference between the nicotine value on the labels
      and the nicotine content in the bottles was 0.3mg/mL (range -5.4 to +3.5mg/mL,
      i.e. -8% to +30%). For 82% of the samples, the actual nicotine content was within
      10% of the value on the labels. All models contained glycerol (median 407mg/mL),
      and all but three models contained propylene glycol (median 650mg/mL). For all
      samples, levels of anabasine, ethylene glycol and diethylene glycol were below
      our limits of detection. The pH of all the e-liquids was alkaline (median pH=9.1;
      range 8.1 to 9.9). The measured content of two batches of the same model varied
      by a median of 0% across batches for propylene glycol, 1% for glycerol, 0% for
      pH, and 0.5% for nicotine (range -15% to +21%; 5th and 95th percentiles: -15% and
      +10%). CONCLUSIONS: The nicotine content of these e-liquids matched the labels on
      the bottles, and was relatively constant across production batches. The content
      of propylene glycol and glycerol was also stable across batches, as was the pH.

PMID- 28511099
TI  - The social exigencies of the gateway progression to the use of illicit drugs from
      adolescence into adulthood.
AB  - BACKGROUND: There is limited empirical integration between peer clustering theory
      and the Gateway framework. The goal of the present study was to test the
      hypothesis that friendship associations partly predict gateway escalations in the
      use of drugs from adolescence to adulthood. METHOD: This longitudinal study
      analyzed 3 waves of data from a community sample of 711 male and female
      participants without a history of illicit drug use reporting drug use at age 17,
      22, and 27. Substance use assessments including tobacco, alcohol, cannabis, onset
      and abuse/dependence tendency of illicit drugs other than cannabis (i.e.,
      cocaine, methamphetamine, and opiates), and friends' reported use of illicit
      drugs. Structural equation modeling was used to test the hypothesized model.
      RESULTS: Participants' cannabis use level at age 17 was positively associated
      with perceived friends' drug use at age 22, which in turn predicted participants'
      onset of illicit drug use between ages 22 and 27. Moreover, progression of
      tobacco use throughout age 17 to 22 was associated with an increased onset of
      illicit drug use between ages 22 and 27. Apart for an effect of cannabis use at
      age 22 on abuse and dependence tendency to various drugs at age 28, results were
      similar. CONCLUSIONS: During this period of development, the availability and
      selection of drug-using friends contributes to the progression to potentially
      more rewarding and damaging illicit drugs. These findings suggest the need to
      attend to the peer ecology in prevention and support the common practice of using
      abstaining peers in treatment for drug dependence.

PMID- 28511100
TI  - Dahlia-shaped BiOClxI1-x structures prepared by a facile solid-state method:
      Evidence and mechanism of improved photocatalytic degradation of rhodamine B dye.
AB  - A rapid and cheap solid-state chemical process was employed to synthesize
      BiOClxI1-x (x=1.0, 0.75, 0.5, 0.25, 0) solid solutions with dahlia-shaped
      hierarchitectures. The dahlia-shaped BiOClxI1-x hierarchitectures were
      effectively constructed by nanoplates with a thickness about 5-13nm. The band gap
      structure of the solid solutions can be modulated by adjusting the composition
      ratio of Cl and I, which has a significant effect on the photocatalytic activity
      of the solid solutions. The dahlia-shaped BiOClxI1-x (x=0.75) solid solution
      exhibits excellent adsorption and effective photocatalytic performances for
      rhodamine B (RhB) under visible light irradiation, which degraded more than 98%
      of RhB within 60min under the visible light irradiation, it is higher than the
      reported bismuth oxyhalides materials. The trapping experiments confirmed that O2
      and h+ played the major role in the photocatalytic process and the possible
      photocatalytic reaction mechanism was illustrated.

PMID- 28511101
TI  - Stable and self-healing superhydrophobic MnO2@fabrics: Applications in self
      cleaning, oil/water separation and wear resistance.
AB  - In this work, superhydrophobic fabrics were prepared through an in-situ growth
      method for fabricating hierarchical flower-like MnO2 nanoparticles on cotton
      fabric surface and subsequent STA modification, which exhibited multifunction for
      self-healing, self-cleaning, oil/water separation and wear resistance. After air
      plasma treatment, the self-healing MnO2@fabric could restore superhydrophobicity
      by a short time heat treatment, and the water CA without obvious reduction after
      8 cycles. Moreover, the MnO2@fabric could selectively filtrate oil from a mixture
      of oil and water repeatedly, and demonstrated high efficiency for oil/water
      separation capability and excellent self-cleaning property. Furthermore, the
      MnO2@fabric composite possessed high mechanical strength and good wear
      resistance, its wear rate could be reduced to 1.21*10-14m3 (Nm)-1. The
      MnO2@fabric still maintained superhydrophobicity even was seriously damaged after
      the friction test.

PMID- 28511102
TI  - Highly effective antibacterial activity by the synergistic effect of three
      dimensional ordered mesoporous carbon-lysozyme composite.
AB  - Aiming at developing a safe and efficient alternative to traditional drinking
      water disinfection, this work successfully synthesized a novel antibacterial
      material with high surface area, ultra large pore size and tunable loading of
      immobilized lysozyme. The immobilized enzymes exhibit high antibacterial efficacy
      without forming carcinogenic disinfection byproducts. Critical immobilization
      parameters were optimized to keep the activity of the immobilized enzyme at a
      high level. The immobilization of lysozymes on 3DOm COOH could be confirmed by
      the characterizations of transmission electron microscopy, X-ray diffraction and
      Zeta-Potential. In addition, the structural stability of lysozymes on 3DOm COOH
      were studied by Fourier transform infrared spectroscopy. The antibacterial
      performance of 3DOm COOH-Lyz were specifically investigated based on the
      disinfection efficacy of Staphylococcus aureus in water. The results revealed
      that the immobilization capacity and relative activity of immobilized lysozyme
      were 814mg/g carrier and 80%, respectively, under the optimal immobilization
      conditions. And the antibacterial material with the initial mass ratio of
      lysozyme and 3DOm COOH as 3:1 exhibited maximum bacteria removal efficiency
      (98.1%) at pH 5. Moreover, the reusability test indicated that 3DOm COOH-Lyz has
      certain operational stability, and remains 82% bacterial removal efficiency even
      in the fifth cycle, which provides a promising application for safe and efficient
      drinking water disinfection in small-scale and emergency water treatment.

PMID- 28511103
TI  - The detection of 'virtual' objects using echoes by humans: Spectral cues.
AB  - Some blind people use echoes to detect discrete, silent objects to support their
      spatial orientation/navigation, independence, safety and wellbeing. The
      acoustical features that people use for this are not well understood. Listening
      to changes in spectral shape due to the presence of an object could be important
      for object detection and avoidance, especially at short range, although it is
      currently not known whether it is possible with echolocation-related sounds.
      Bands of noise were convolved with recordings of binaural impulse responses of
      objects in an anechoic chamber to create 'virtual objects', which were analysed
      and played to sighted and blind listeners inexperienced in echolocation. The
      sounds were also manipulated to remove cues unrelated to spectral shape. Most
      listeners could accurately detect hard flat objects using changes in spectral
      shape. The useful spectral changes for object detection occurred above
      approximately 3 kHz, as with object localisation. However, energy in the sounds
      below 3 kHz was required to exploit changes in spectral shape for object
      detection, whereas energy below 3 kHz impaired object localisation. Further
      recordings showed that the spectral changes were diminished by room
      reverberation. While good high-frequency hearing is generally important for
      echolocation, the optimal echo-generating stimulus will probably depend on the
      task.

PMID- 28511104
TI  - Lumbar extensor muscle force control is associated with disability in people with
      chronic low back pain.
AB  - BACKGROUND: The ability to control lumbar extensor force output is necessary for
      daily activities. However, it is unknown whether this ability is impaired in
      chronic low back pain patients. Similarly, it is unknown whether lumbar extensor
      force control is related to the disability levels of chronic low back pain
      patients. METHODS: Thirty-three chronic low back pain and 20 healthy people
      performed lumbar extension force-matching task where they increased and decreased
      their force output to match a variable target force within 20%-50% maximal
      voluntary isometric contraction. Force control was quantified as the root-mean
      square-error between participants' force output and target force across the
      entire, during the increasing and decreasing portions of the force curve. Within-
      and between-group differences in force-matching error and the relationship
      between back pain group's force-matching results and their Oswestry Disability
      Index scores were assessed using ANCOVA and linear regression respectively.
      FINDINGS: Back pain group demonstrated more overall force-matching error (mean
      difference=1.60 [0.78, 2.43], P<0.01) and more force-matching error while
      increasing force output (mean difference=2.19 [1.01, 3.37], P<0.01) than control
      group. The back pain group demonstrated more force-matching error while
      increasing than decreasing force output (mean difference=1.74, P<0.001, 95%CI
      [0.87, 2.61]). A unit increase in force-matching error while decreasing force
      output is associated with a 47% increase in Oswestry score in back pain group
      (R2=0.19, P=0.006). INTERPRETATION: Lumbar extensor muscle force control is
      compromised in chronic low back pain patients. Force-matching error predicts
      disability, confirming the validity of our force control protocol for chronic low
      back pain patients.

PMID- 28511105
TI  - Quadriceps rate of torque development and disability in individuals with anterior
      cruciate ligament reconstruction.
AB  - BACKGROUND: The purpose of this study was to determine associations between self
      reported function (International Knee Documentation Committee Index), isometric
      quadriceps strength and rate of torque development in individuals with a
      unilateral anterior cruciate ligament reconstruction. METHODS: Forty-one
      individuals [31% male, BMI mean 25 (SD 4) kg/m2, months post anterior cruciate
      ligament reconstruction mean 49 (SD 40)] completed the self-reported function and
      isometric quadriceps function testing. Rate of torque development was assessed at
      0-100ms (early), 100-200ms (late) ms, and peak following the onset of
      contraction. Associations were examined between rate of torque development,
      strength, and self-reported function. Linear regression was used to determine the
      unique amount of variance explained by the combination of rate of torque
      development and strength. FINDINGS: Higher rate of torque development 100-200ms
      is weakly associated with higher self-reported function in individuals with a
      unilateral anterior cruciate ligament reconstruction (r=0.274, p=0.091); however,
      rate of torque development 100-200ms does not predict a significant amount of
      variance in self-reported function after accounting for strength (DeltaR2=0.003,
      P=0.721). INTERPRETATION: Quadriceps strength has a greater influence on self
      reported function compared to rate of torque development in individuals with an
      anterior cruciate ligament reconstruction with time from surgery.

PMID- 28511106
TI  - Mechanical properties and numerical simulation of Sulcata tortoise carapace.
AB  - Carapace of Sulcata tortoise acts as a natural shield that protects the body from
      natural predators. The carapace consists of four layers: keratin scutes, dorsal
      cortex, cancellous interior and ventral cortex. This study aims to investigate
      the load-bearing mechanisms of the carapace by characterizing the layers,
      measuring their mechanical properties and relating them to the macroscopic
      behavior under compression and bending loads. Test results indicate the influence
      of layers' morphology, especially porosity and structural compositions, on the
      macroscopic properties of the carapace. The bending samples are simulated using a
      commercial finite element code as laminate composite structures with homogeneous
      elastic layers. The models are shown to capture the load-displacement response of
      the carapace in the elasticity regime under quasi-static loadings.

PMID- 28511107
TI  - Frequent emergency department presentations among people who inject drugs: A
      record linkage study.
AB  - BACKGROUND: People who inject drugs (PWID) have been described as frequent users
      of health services such as emergency departments (EDs), however few studies have
      described demographic factors, patterns of substance use and previous health
      service use associated with frequent use of EDs in this population. METHODS:
      Using a combination of self-reported data from a cohort of PWID and
      administrative ED data obtained through record linkage, we identified
      longitudinal factors associated with the use of ED services. Bivariate and
      multivariate analyses were conducted using negative binomial regression to
      identify exposures associated with both cumulative ED presentations, and logistic
      regression to identify exposures of frequent ED presentations (defined as three
      or more annual presentations). RESULTS: Among 612 PWID, over half (58%) presented
      to EDs at least once and over a third (36%) presented frequently between January
      2008 and June 2013. Frequent and cumulative ED presentations were associated with
      reporting the main drug of choice as cannabis (AOR:1.42, 95%CI:1.07-1.89 and
      AIRR:2.96, 95%CI:1.44-6.07 respectively) or methamphetamine (AOR:1.62, 95%CI:1.17
      2.2 and AIRR:2.42, 95%CI:1.08-5.46 respectively) compared to heroin, and past
      month use of mental health (AOR:1.42, 95%CI:1.08-1.85 and AIRR:3.32, 95%CI:1.69
      6.53 respectively) and outpatient services (AOR:1.47, 95%CI: 1.00-2.16 and
      AIRR:0.95, 95%CI 1.52-10.28 respectively). CONCLUSION: PWID who are frequent
      users of EDs are likely to have complex health and substance use-related needs.
      EDs should actively refer people who present with cannabis and methamphetamine
      dependence to harm reduction services. Harm reduction services should ensure
      people referred from EDs are screened for co-occurring mental health conditions
      and receive adequate support.

PMID- 28511108
TI  - Wine yeasts identification by MALDI-TOF MS: Optimization of the preanalytical
      steps and development of an extensible open-source platform for processing and
      analysis of an in-house MS database.
AB  - Saccharomyces cerevisiae is the most important yeast species for the production
      of wine and other beverages. In addition, nowadays, researchers and winemakers
      are aware of the influence of non-Saccharomyces in wine aroma complexity. Due to
      the high microbial diversity associated to several agro-food processes, such as
      winemaking, developing fast and accurate methods for microbial identification is
      demanded. In this context, MALDI-TOF MS mass fingerprint provides reliable tool
      for fast biotyping and classification of microorganisms. However, there is no
      versatile and standardized method for fungi currently available. In this study,
      an optimized sample preparation protocol was devised for the biotyping of yeasts
      of oenological origin. Taking into account that commercially available reference
      databases comprise almost exclusively clinical microorganisms, most of them
      bacteria, in the present study a database of yeasts isolated from vineyards and
      wineries was created, and its accuracy was tested using industrial and laboratory
      yeast strains. In addition, the implementation of a program for MALDI-TOF MS
      spectra analysis has been developed as an extensible open-source platform for
      MALDI data processing and analysis with statistical techniques that has arisen
      from our previous experience working with MALDI data. The software integrates two
      R packages for raw MALDI data preprocessing: Continuous Wavelet Transform (CWT)
      based algorithm and MassSpecWavelet. One of the advantages of the CWT is that it
      can be directly applied to a raw spectrum, without prior baseline correction.
      Mass fingerprints of 109 S. cerevisiae strains and 107 non-Saccharomyces isolates
      were generated by MALDI-TOF MS upon optimized sample preparation and instrument
      settings and analyzed for strain, species, and genus-level differentiation. As a
      reference method, for S. cerevisiae differentiation at strain level, the analysis
      of the polymorphism in the inter-delta region was chosen. The data revealed that
      MALDI-TOF MS can be used for the rapid and accurate identification of S.
      cerevisiae and non-Saccharomyces isolates at genus and species level. However, S.
      cerevisiae differentiation at strain level was not successfully achieved, and the
      differentiation among Metschnikowia species was also difficult.

PMID- 28511109
TI  - Sensitive detection of viable Escherichia coli O157:H7 from foods using a
      luciferase-reporter phage phiV10lux.
AB  - Escherichia coli O157:H7, a major foodborne pathogen, is a major public health
      concern associated with life-threatening diseases such as hemolytic uremic
      syndrome. To alleviate this burden, a sensitive and rapid system is required to
      detect this pathogen in various kinds of foods. Herein, we propose a phage-based
      pathogen detection method to replace laborious and time-consuming conventional
      methods. We engineered an E. coli O157:H7-specific phage phiV10 to rapidly and
      sensitively detect this notorious pathogen. The luxCDABE operon was introduced
      into the phiV10 genome and allowed the engineered phage phiV10lux to generate
      bioluminescence proportional to the number of viable E. coli O157:H7 cells
      without any substrate addition. The phage phiV10lux was able to detect at least
      1CFU/ml of E. coli O157:H7 in a pure culture within 40min after 5h of pre
      incubation. In artificially contaminated romaine lettuce, apple juice (pH3.51),
      and ground beef, the reporter phage could detect approximately 10CFU/cm2,
      13CFU/ml, and 17CFU/g of E. coli O157:H7, respectively. Taken together, the
      constructed reporter phage phiV10lux could be applied as a powerful tool for
      rapid and sensitive detection of live E. coli O157:H7 in foods.

PMID- 28511110
TI  - Determination of regional relationships among Salmonella spp. isolated from
      retail pork circulating in the Chiang Mai municipality area using a WGS data
      approach.
AB  - Salmonella is recognized as a significant zoonotic foodborne pathogen, and pork
      products are involved in one-fifth of infections. Whole genome sequencing data of
      Salmonella isolated from retail's pork circulating in the Chiang Mai Municipality
      area between April 2013 and September 2014, were used to focus on genetic
      diversity and proven in pig-human transmission based on Multilocus Sequence
      Typing (MLST). Additionally, WGS data were used to investigate virulence genes,
      to assess the hazard or pathogenic potential transferred into the food production
      chain. In this study, all 32 Salmonella strains were classified into 11 Sequence
      Types (STs). ST469 accounted for the majority (41%). The sequence types of two
      other strains, 6% of the total, could not be identified. All tested strains
      carried at least 15 virulence genes. The most frequent gene profile was "sfm-fim
      sop-inv.-org-sip-spa-sif-fli-flg-hil-spr-ssa-sse-pag-bss" (47%). Salmonella
      circulating in the study area demonstrated competence in biofilm production, host
      cell adhesion, host cell invasion, and host cell survival. Based on the
      phenotypic and genotypic findings, as well as pathogen source, it appears
      possible that a common supply chain or common infection source might be presented
      in the retail pork system in the study area. In addition, an epidemiological
      comparison of the Salmonella genotypes from the current study with those from
      other areas such as People's Republic of China (PR China) and the Lao People's
      Democratic Republic (Lao PDR) was generated by Minimum spanning tree (MST).
      Identical strains originating from humans, animals and food were found. The
      findings indicate that contamination can be occured at all levels including pre
      harvest, the farm-slaughterhouse-retail chain and consumers over different
      geographical areas. Acquiring information about infection sources and
      transmission routes will hopefully motivate all sectors to enforce strict
      sanitation controls at all production stages including the consumer level.

PMID- 28511111
TI  - Adaptive conditions and safety of the application of Penicillium frequentans as a
      biocontrol agent on stone fruit.
AB  - Penicillium frequentans (Pf909) reduces brown rot caused by Monilinia spp. in
      stone fruit. The registration of a microbial biocontrol agent in Europe requires
      information on the risks and safety of a biological product. This study focused
      on the impact of the physical environment on Pf909 survival and growth, Pf909
      mycotoxin production on fruit surface, and the Pf909 resistance to commercial
      antifungal compounds used in animal and human medicine. The effect of temperature
      (4 to 37 degrees C), water activity (0.999 to 0.900), pH (3 to 11), light
      intensity (0, 90 and 180lm) and photoperiod (0/24, 12/12, 16/8, 24/0; light/dark)
      on mycelial growth and sporulation of Pf909 were monitored for 10days in vitro on
      culture medium. Antifungal activity of antifungal compounds on mycelial growth of
      Pf909 was also measured by a quantitative micro spectrophotometric assay after
      72h of incubation. The presence or absence of four non-volatile mycotoxins
      (patulin, penicillic acid, ochratoxin A and citrinin) on nectarine surfaces
      treated with Pf909 was determined by HPLC. Growth rate was significantly
      influenced by water activity, temperature and light exposure conditions. Pf909
      showed maximum growth and sporulation at 22 degrees C and 25 degrees C, in wet
      conditions (0.999 water activity), with a pH5.6 to 9, and in darkness or a short
      light photoperiod. Our results showed all antifungal compounds used reduced
      significantly Pf909 mycelial growth at tested commercial doses. HPLC data
      analysis showed that 7days after biofungicide (Pf909) application there were no
      mycotoxin products on the surface of nectarine. Finally, no phylogenetic
      relationship has been shown among Pf909 and other species of Penicillium that
      produce mycotoxins. In conclusion, from an ecological point of view, Pf909 would
      establish and survive actively over a broad range of climatic conditions. The
      probability of risks to human and animal health is considered very low.

PMID- 28511112
TI  - Real-time fluorescence assay of alkaline phosphatase in living cells using boron
      doped graphene quantum dots as fluorophores.
AB  - This work reports a convenient and real-time assay of alkaline phosphatase (ALP)
      in living cells based on a fluorescence quench-recovery process at a
      physiological pH using the boron-doped graphene quantum dots (BGQDs) as
      fluorophore. The fluorescence of BGQDs is found to be effectively quenched by
      Ce3+ ions because of the coordination of Ce3+ ions with the carboxyl group of
      BGQDs. Upon addition of adenosine triphosphate (ATP) into the system, the
      quenched fluorescence can be recovered by the ALP-positive expressed cells (such
      as MCF-7 cells) due to the removal of Ce3+ ions from BGQDs surface by phosphate
      ions, which are generated from ATP under catalytic hydrolysis of ALP that
      expressed in cells. The extent of fluorescence signal recovery depends on the
      level of ALP in cells, which establishes the basis of ALP assay in living cells.
      This approach can also be used for specific discrimination of the ALP expression
      levels in different type of cells and thus sensitive detection of those ALP
      positive expressed cells (for example MCF-7 cells) at a very low abundance (10+/
      5 cells mL-1). The advantages of this approach are that it has high sensitivity
      because of the significant suppression of the background due to the Ce3+ ion
      quenching the fluorescence of BGQDs, and has the ability of avoiding false
      signals arising from the nonspecific adsorption of non-target proteins because it
      operates via a fluorescence quench-recovery process. In addition, it can be
      extended to other enzyme systems, such as ATP-related kinases.

PMID- 28511113
TI  - Turn-on theranostic fluorescent nanoprobe by electrostatic self-assembly of
      carbon dots with doxorubicin for targeted cancer cell imaging, in vivo
      hyaluronidase analysis, and targeted drug delivery.
AB  - This paper reports a turn-on theranostic fluorescent nanoprobe P-CDs/HA-Dox
      obtained by electrostatic assembly of polyethylenimine (PEI)-modified carbon dots
      (P-CDs) and Hyaluronic acid (HA)-conjugated doxorubicin (Dox) for hyaluronidase
      (HAase) detection, self-targeted imaging and drug delivery. P-CDs/HA-Dox show
      weak emission in a physiological environment. By utilizing the high affinity of
      HA to CD44 receptors overexpressed on many cancer cells, P-CDs/HA-Dox are capable
      of targeting and penetrating into cancer cells, where they are activated by
      HAase. As a result, HA-Dox can be digested into small fragments, causing the
      release of Dox and thereby restoring the fluorescence of P-CDs. The theranostic
      fluorescent nanoprobe can effectively distinguish cancer cells from normal cells.
      The as-prepared nanoprobe achieves a sensitive assay of HAase with a detection
      limit of 0.65UmL-1. Furthermore, upon Dox release, the Dox could efficiently
      induce apoptosis in HeLa cells, as confirmed by MTT assay. The design of such a
      turn-on theranostic fluorescent probe provides a new strategy for self-targeted
      and image-guided chemotherapy.

PMID- 28511114
TI  - Bergapten prevents lipopolysaccharide-induced inflammation in RAW264.7 cells
      through suppressing JAK/STAT activation and ROS production and increases the
      survival rate of mice after LPS challenge.
AB  - Bergapten (BG) is a cumarine-derivate compound in many medicinal plants. Here, in
      vitro and in vivo experimental results indicated that BG possesses anti
      inflammatory properties, Based on this, we further investigated the precise
      molecular mechanisms of BG in LPS-stimulated inflammation response. Studies
      revealed that BG inhibited LPS-stimulated productions of TNF-alpha, IL-1beta, IL
      6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time,
      it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7
      cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that
      of MAPKs and NF-kappaB. In addition, BG, as an antioxidant, prevented the
      accumulation of ROS, which further exerted its anti-inflammatory function. In
      vivo researches revealed that BG decreased LPS-induced mortality in mice. In
      conclusions, BG may be a potential candidate for inflammation therapy via
      inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.

PMID- 28511115
TI  - Apoplastic ROS signaling in plant immunity.
AB  - Reactive oxygen species (ROS) are widely produced in different cellular
      compartments under both biotic and abiotic stress conditions. ROS play a central
      role in plant signaling and regulate diverse cellular processes. Recent advances
      are shedding new light on sophisticated mechanisms controlling ROS biogenesis and
      signaling in plant immunity. In this review, we summarize our current
      understanding of the regulation of apoplastic ROS production in response to
      microbial molecular patterns and draw comparison with abscisic acid (ABA)-induced
      apoplastic ROS. We also discuss how ROS act as signal molecules to regulate
      cellular activities using stomatal movement as an example.

PMID- 28511116
TI  - Functional RNA structures throughout the Hepatitis C Virus genome.
AB  - The single-stranded Hepatitis C Virus (HCV) genome adopts a set of elaborate RNA
      structures that are involved in every stage of the viral lifecycle. Recent
      advances in chemical probing, sequencing, and structural biology have facilitated
      analysis of RNA folding on a genome-wide scale, revealing novel structures and
      networks of interactions. These studies have underscored the active role played
      by RNA in every function of HCV and they open the door to new types of RNA
      targeted therapeutics.

PMID- 28511117
TI  - Conditioned medium from relapsing-remitting multiple sclerosis patients reduces
      the expression and release of inflammatory cytokines induced by LPS-gingivalis in
      THP-1 and MO3.13 cell lines.
AB  - The present research was aimed at evaluating the effect of the conditioned medium
      (CM) from human periodontal ligament stem cells (hPDLSCs) obtained from healthy
      donors (hPDLSCs-CM) and from Relapsing-Remitting Multiple Sclerosis patients (RR
      MS-CM) on inflammatory response induced by Porphyromonas gingivalis
      lipopolysaccharide (LPS-G) in a monocytoid human cell line (THP-1) and human
      oligodendrocyte cell line (MO3.13). Human periodontal ligament biopsies were
      carried out from control donor patients and selected RR-MS donors. Sample tissues
      were obtained from premolar teeth during root scaling and subsequently cultured.
      The effect of hPDLSCs-CM and RR-MS-CM on cell viability in PMA differentiated THP
      1 (as a model of microglia) was measured using a 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay. The same experiments were performed in
      undifferentiated and differentiated MO3.13 cells used as models of progenitor
      cells and oligodendrocytes, respectively. The expression of tumor necrosis factor
      alpha (TNF)-alpha, interleukin (IL)-1beta and IL-6 was evaluated by Real-Time
      Polymerase Chain Reaction (RT-PCR), and enzyme-linked immunosorbent assay
      (ELISA). The expression level of the Toll-like receptor 4 (TLR-4), for which LPS
      G is a ligand, was evaluated by Western blot analysis. The results were analyzed
      by ANOVA using Graph Pad Prism software. LPS-G significantly increased TNFalpha,
      IL-1beta and IL-6 mRNA expression and protein levels in the differentiated THP-1
      cells and oligodendrocyte MO3.13 progenitor cells. Treatment with hPDLSCs-CM or
      with RR-MS-CM significantly attenuated the LPS-induced expression and production
      of these pro-inflammatory cytokines. The CM from both healthy donors and RR-MS
      patients also reduced the LPS-G stimulated protein levels of TLR-4 in
      differentiated THP-1 cells. On the whole our data add new evidence on the anti
      inflammatory effects of these peculiar stem cells even when derived from RR-MS
      patients and open novel perspectives in the therapeutic use of autologous
      periodontal stem cells in neuroinflammatory/neurodegenerative diseases including
      MS.

PMID- 28511118
TI  - Simultaneous determination of selective serotonin reuptake inhibitors and their
      main metabolites in human breast milk by liquid chromatography-electrospray mass
      spectrometry.
AB  - A bioanalytical method by high performance liquid chromatography coupled to
      electrospray mass spectrometry (HPLC-ESI-MS), adapted from a previously published
      method in plasma, was validated in breast milk for the simultaneous
      quantification of all antidepressants belonging to the class of selective
      serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine
      and sertraline) and their major metabolites (desmethylcitalopram and
      norfluoxetine). Milk samples (250MUl) first underwent protein precipitation
      followed by solid-phase extraction on a reversed phase/cation exchange sorbent.
      Analytes were thereafter separated on a XBridge C18 column (2.1mm*100mm; 3.5MUm)
      using a mobile phase composed of ammonium acetate buffer (pH 8.1; 50mM) and
      acetonitrile in gradient mode. Detection was performed by a single quadrupole
      mass spectrometer running in selected ion monitoring in positive ionization mode.
      Method validation covered a wide concentration range of 2-500ng/ml for
      citalopram, desmethylcitalopram and paroxetine, 5-500ng/ml for sertraline, and 2
      1000ng/ml for fluoxetine, norfluoxetine and fluvoxamine. Validation performances
      such as trueness (90.3-111.6%), repeatability (0.8-9.3%) and intermediate
      precision (0.9-9.5%) were in agreement with criteria from international
      guidelines and matrix effects for the analyte/internal standard ratios ranged
      from 92% to 110% (relative standard deviation <15%). Accuracy profiles (total
      error of trueness and precision) were lying within the limits of +/-30% accepted
      in bioanalysis. Finally, the method was successfully applied to patient samples
      collected in a clinical pharmacokinetic study of nursing mothers taking an
      antidepressant treatment.

PMID- 28511120
TI  - Stokes flow patterns induced by a single cardiac cell.
AB  - Stokes flow motions induced by a beating single cardiac cell (cardiomyocyte) are
      obtained numerically using the method of fundamental solutions (MFS). A two
      dimensional meshfree-Stokeslets computational framework is used to solve the
      Stokes governing equations around an isolated cardiomyocyte. An approximate
      beating kinematical model is derived and used to approximate the cell-length
      shortening over a complete cardiac cycle. The induced flow patterns have been
      found to be characterized by the presence of counter-rotating vortices at both
      cell's edges. These vortical flow structures are clearly shown by rendering the
      velocity streamlines. The static pressure contours are also calculated at
      different time snapshots during both contraction and relaxation phases of the
      beating motion. The pressure signal is calculated at a point in the neighborhood
      of cell surface to capture the induced normal stress (traction) by the cell
      morphological motions to the surrounding fluid medium. The presented results have
      shown that, cells with a slightly different shortening/beating profile can induce
      different flow field. This implies that, each cell is characterized by a unique
      flow pattern "signature", which potentially can be correlated to the sub-cellular
      excitation-contraction processes of cardiac cells.

PMID- 28511119
TI  - Effects of breviscapine on amyloid beta 1-42 induced Alzheimer's disease mice: A
      HPLC-QTOF-MS based plasma metabonomics study.
AB  - Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial
      pain in China. In addition, the bioactivities of its total flavonoids
      breviscapine included inhibiting amyloid beta (Abeta) fibril formation,
      antioxidation and metal chelating, which are beneficial to treat Alzheimer's
      disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was
      applied to investigate the neuroprotective effects of breviscapine on
      intracerebroventricular injection of aggregated Abeta 1-42 induced AD mice for
      the first time in the study. Ten potential biomarkers were screened out by
      multivariate statistical analysis, eight of which were further identified as
      indoleacrylic acid, C16 sphinganine, LPE (22:6), sulfolithocholic acid, LPC
      (16:0), PA (22:1/0:0), taurodeoxycholic acid, and PC (0:0/18:0). According to
      their metabolic pathways, it was supposed that breviscapine ameliorated the
      learning and memory deficits of AD mice predominantly by regulating phospholipids
      metabolism, elevating serotonin level and lowering cholesterols content in vivo.

PMID- 28511121
TI  - Influence of different frequencies of axial cyclic loading on time-domain
      vibration response of the lumbar spine: A finite element study.
AB  - Very few studies have quantitatively analyzed influence of the loading frequency
      on time-domain vibration response of the whole lumbar spine in the presence of a
      physiologic compressive preload. In this study, a three-dimensional non-linear
      finite element model of ligamentous L1-S1 segment was developed to predict time
      domain dynamic response of the whole lumbar spine to axial cyclic loading with
      different frequencies. A compressive follower preload of 400 N was applied to the
      model to simulate the physiologic compressive load. Modal analysis was initially
      performed to extract axial resonant frequency of the model under a 40 kg upper
      body mass and the 400 N preload. The result showed that the axial resonant
      frequency was 7.77 Hz. Subsequently, transient dynamic analyses were performed on
      the model under a sinusoidal axial load of +/-40 N at frequencies of 3, 5, 7, 9,
      11, 13 and 15 Hz with the 400 N preload and 40 kg mass. The computational results
      (strains and stresses in the spinal components) were collected and plotted as a
      function of time. These predicted results were found to be frequency-dependent
      and consistent with the notion in engineering dynamics texts that the closer the
      loading frequency approaches the resonant frequency, the larger the response is.
      For example, the results for 5 Hz load compared to 3 Hz load showed a 68.6-111.5%
      increase in peak-to-bottom variations of the predicted response parameters, and
      the results for 13 Hz load compared to 11 Hz load showed a 26.4-37.8% decrease in
      these variations.

PMID- 28511122
TI  - Robotic assessment of neuromuscular characteristics using musculoskeletal models:
      A pilot study.
AB  - OBJECTIVE: Non-invasive neuromuscular characterization aims to provide greater
      insight into the effectiveness of existing and emerging rehabilitation therapies
      by quantifying neuromuscular characteristics relating to force production, muscle
      viscoelasticity and voluntary neural activation. In this paper, we propose a
      novel approach to evaluate neuromuscular characteristics, such as muscle fiber
      stiffness and viscosity, by combining robotic and HD-sEMG measurements with
      computational musculoskeletal modeling. This pilot study investigates the
      efficacy of this approach on a healthy population and provides new insight on
      potential limitations of conventional musculoskeletal models for this
      application. METHODS: Subject-specific neuromuscular characteristics of the
      biceps and triceps brachii were evaluated using robot-measured kinetics,
      kinematics and EMG activity as inputs to a musculoskeletal model. RESULTS:
      Repeatability experiments in five participants revealed large variability within
      each subjects evaluated characteristics, with almost all experiencing variation
      greater than 50% of full scale when repeating the same task. CONCLUSION: The use
      of robotics and HD-sEMG, in conjunction with musculoskeletal modeling, to
      quantify neuromuscular characteristics has been explored. Despite the ability to
      predict joint kinematics with relatively high accuracy, parameter
      characterization was inconsistent i.e. many parameter combinations gave rise to
      minimal kinematic error. SIGNIFICANCE: The proposed technique is a novel approach
      for in vivo neuromuscular characterization and is a step towards the realization
      of objective in-home robot-assisted rehabilitation. Importantly, the results have
      confirmed the technical (robot and HD-sEMG) feasibility while highlighting the
      need to develop new musculoskeletal models and optimization techniques capable of
      achieving consistent results across a range of dynamic tasks.

PMID- 28511123
TI  - Dismissing the goals: A comparison of four goal-dismissive goal-free evaluations.
AB  - This article provides a descriptive review of four goal-free evaluations (GFE).
      GFE is an evaluation model where the evaluator conducts the evaluation without
      knowledge of or reference to the evaluand's stated goals. The four non-randomly
      sampled evaluation approaches represent articulated evaluation models in which
      the evaluators ignore the goals of the intervention or project. Data collection
      consisted of document analyses supplemented by semi-structured interviews with
      the models' creators. The findings from these case studies include descriptions
      of the evaluation models, the models' relationship to GFE, and eight
      commonalities shared among the four models. The conclusion of this study is that
      these GFEs are similar to other GFEs described in the literature in that they
      examine outcomes as reported by the intervention's consumers, focus on collecting
      qualitative data, and use their evaluations to supplement a larger goal-based
      evaluation strategy.

PMID- 28511124
TI  - Demonstration of short-term plasticity in the dorsolateral prefrontal cortex with
      theta burst stimulation: A TMS-EEG study.
AB  - OBJECTIVES: To examine the effects of intermittent TBS (iTBS) and continuous TBS
      (cTBS) on cortical reactivity in the dorsolateral prefrontal cortex. METHODS: 10
      healthy participants were stimulated with either iTBS, cTBS or sham at F3
      electrode. Single- and paired-pulse TMS and concurrent electroencephalography
      (EEG) were used to assess change in cortical reactivity and long-interval
      intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked
      oscillations. RESULTS: Significant increases in N120 amplitudes (p<0.01) were
      observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta
      oscillations and LICI of theta oscillations were also observed following iTBS
      (increase) and cTBS (decrease). Change in LICI of theta oscillations correlated
      with change in N120 amplitude following TBS (r=-0.670, p=0.001). CONCLUSIONS:
      This study provides preliminary evidence that TBS produces direct changes in
      cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a
      useful approach to optimise stimulation paradigms prior to the conduct of
      clinical trials. SIGNIFICANCE: TBS is able to modulate cortical reactivity and
      cortical inhibition in the prefrontal cortex.

PMID- 28511126
TI  - Endophenotyping in idiopathic adult onset cervical dystonia.
AB  - OBJECTIVE: Idiopathic adult onset cervical dystonia (IAOCD) is considered to be a
      partially penetrant autosomal dominant genetic condition. Dystonia may result
      from genetic and environmental factors. In this view, part of the physiology
      should be an endophenotype stemming from the genetic background. We assessed the
      most discriminative test to separate patients with IAOCD and healthy controls for
      further endophenotyping in non-affected 1st degree relatives. METHODS: We
      included patients with IAOCD, their 1st degree relatives and healthy controls.
      Tests performed: (1) Sensory temporal discrimination (visual, tactile, visuo
      tactile), (2) Paired pulse paradigms using transcranial magnetic stimulation
      (TMS), (3) Mental rotation paradigms. RESULTS: 45 patients with IAOCD, 23 healthy
      controls and 14 non-affected 1st degree relatives were recruited. Visuo-tactile
      temporal discrimination separated best between controls and patients as well as
      between controls and 1st degree relatives. 36% of the latter had an abnormal
      visuo-tactile temporal discrimination. No difference between patients and healthy
      controls was found for the other paradigms. CONCLUSIONS: Visuo-tactile temporal
      discrimination separates controls from patients with IAOCD and its 1st degree
      relatives. 36% of the latter had abnormal visuo-tactile thresholds supporting the
      role of visuo-tactile temporal discrimination as an endophenotype for IAOCD.
      SIGNIFICANCE: Even though the study was of exploratory design, our findings
      expand the understanding of endophenotypes in IAOCD.

PMID- 28511127
TI  - Neurophysiology of synaptic functioning in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory immune-mediate disorder of the central
      nervous system (CNS), primarily affecting the myelin sheath and followed by
      neurodegeneration. Synaptic alterations are emerging as critical determinants of
      early neurodegeneration in MS. Inflammation-induced alterations of synaptic
      transmission and plasticity have been investigated in vitro and also in human MS
      using transcranial magnetic stimulation (TMS) techniques. Specific inflammatory
      cytokines alter glutamatergic and GABAergic transmission, resulting in synaptic
      hyperexcitability. In both experimental autoimmune encephalomyelitis (EAE) and
      MS, excitotoxic damage and neurodegeneration are found even in the early phases
      of disease, conversely inflammation persists in the progressive phases.
      Inflammatory cytokines also affect synaptic plasticity, as both long-term
      potentiation (LTP) and long-term depression (LTD) are altered in EAE and in MS
      patients. In particular, inflammation profoundly subverts plasticity and
      influence both clinical recovery after a relapse and disease course. Regulation
      of neuronal activity by cytokines plays important roles in the neuro-immune
      crosstalk involved in inflammation-associated excitotoxic neuronal damage, and in
      the chance of developing compensatory plasticity. Innate and adaptive immunity
      interact with the CNS in MS, in line with the concept that cytokines and
      chemokines, in concert with neurotransmitters and neuropeptides, represent a
      major communication system in the CNS.

PMID- 28511128
TI  - Improving the repeatability of Motor Unit Number Index (MUNIX) by introducing
      additional epochs at low contraction levels.
AB  - OBJECTIVE: To evaluate the repeatability of (Motor Unit Number Index) MUNIX under
      repeatability conditions, specify the origin of variations and provide strategies
      for quality control. METHODS: MUNIX calculations were performed on the bicep
      brachii muscles of eight healthy subjects. Negative effect of suboptimal
      electrode positions on MUNIX accuracy was eliminated by employing the high
      density surface electromyography technique. MUNIX procedures that utilized a
      variety of surface interferential pattern (SIP) epoch recruitment strategies
      (including the original MUNIX procedure, two proposed improvement strategies and
      their combinations) were described. For each MUNIX procedure, ten thousands of
      different SIP pools were constructed by randomly recruiting necessary SIP epochs
      from a large SIP epoch pool (3 datasets, 9 independent electromyography
      recordings at different contraction levels per dataset and 10 SIP epochs per
      recording) and implemented for MUNIX calculation. The repeatability of each MUNIX
      procedure was assessed by summarizing the resulting MUNIX distribution and
      compared to investigate the effect of SIP epoch selection strategy on
      repeatability performance. RESULTS: SIP epochs selected at lower contraction
      levels have a stronger influence on the repeatability of MUNIX than those
      selected at higher contraction levels. MUNIX under repeatability conditions
      follows a normal distribution and the standard deviation can be significantly
      reduced by introducing more epochs near the MUNIX definition line. CONCLUSIONS:
      The MUNIX technique shows an inherent variation attributable to SIP epochs at low
      contraction levels. It is recommended that more epochs should be sampled at these
      low contraction levels to improve the repeatability. SIGNIFICANCE: The present
      study thoroughly documented the inherent variation of MUNIX and the causes, and
      offered practical solutions to improve the repeatability of MUNIX.

PMID- 28511129
TI  - Neurophysiological and clinical outcomes in chemotherapy-induced neuropathy in
      cancer.
AB  - Chemotherapy induced peripheral neuropathy (CIPN) is a significant toxicity of
      cancer treatment, with the potential to affect long-term function and quality of
      life in cancer survivors. There remains a lack of consensus around optimal
      assessment techniques. While current approaches to CIPN assessment are focused on
      clinical grading scales, it is becoming increasingly evident that a more
      comprehensive multimodal assessment package is necessary to accurately
      characterise the impact of CIPN as well as gauge the utility of neuroprotective
      mechanisms. Neurophysiological techniques provide objective biomarkers and may
      enable early detection of toxicity while patient reported outcomes are necessary
      to determine the significance of symptoms to individual patients. In addition to
      providing an objective assessment, clinical neurophysiological techniques provide
      important insights into the contributory pathophysiological mechanisms of CIPN
      with different chemotherapy agents. There is a paucity of implementation of these
      techniques in the clinical trial setting. The present Review aims to facilitate
      the use of neurophysiological studies as part of comprehensive assessment
      packages for the monitoring of CIPN by summarising current understanding of
      neurophysiological changes that underlie the development of neuropathy, clinical
      presentations and patient reported outcomes as well as advantages and limitations
      of current techniques for the neurophysiological assessment of CIPN.

PMID- 28511125
TI  - The many facets of motor learning and their relevance for Parkinson's disease.
AB  - The final goal of motor learning, a complex process that includes both implicit
      and explicit (or declarative) components, is the optimization and automatization
      of motor skills. Motor learning involves different neural networks and
      neurotransmitters systems depending on the type of task and on the stage of
      learning. After the first phase of acquisition, a motor skill goes through
      consolidation (i.e., becoming resistant to interference) and retention, processes
      in which sleep and long-term potentiation seem to play important roles. The
      studies of motor learning in Parkinson's disease have yielded controversial
      results that likely stem from the use of different experimental paradigms. When a
      task's characteristics, instructions, context, learning phase and type of
      measures are taken into consideration, it is apparent that, in general, only
      learning that relies on attentional resources and cognitive strategies is
      affected by PD, in agreement with the finding of a fronto-striatal deficit in
      this disease. Levodopa administration does not seem to reverse the learning
      deficits in PD, while deep brain stimulation of either globus pallidus or
      subthalamic nucleus appears to be beneficial. Finally and most importantly,
      patients with PD often show a decrease in retention of newly learned skill, a
      problem that is present even in the early stages of the disease. A thorough
      dissection and understanding of the processes involved in motor learning is
      warranted to provide solid bases for effective medical, surgical and
      rehabilitative approaches in PD.

PMID- 28511130
TI  - Design, synthesis and biological evaluation of uncharged catechol derivatives as
      selective inhibitors of PTP1B.
AB  - Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic
      target to effectively treat T2DM and obesity. However, the development of charged
      PTP1B inhibitors was restricted due to their low cell permeability and poor
      bioavailability. Based on active natural products, two series of uncharged
      catechol derivatives were identified as PTP1B inhibitors by targeting a secondary
      aryl phosphate-binding site as well as the catalytic site. The most potent
      inhibitor 22 showed an IC50 of 0.487 MUM against PTP1B and strong selectivity (27
      fold) over TCPTP. Kinetic studies were also performed that 22 act as a
      competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly
      increased the phosphorylation levels of IRbeta, Akt and IRS1 phosphorylation. The
      similarity of its action profiling with that produced by insulin suggested its
      potential as a new non-insulin-dependent drug candidate.

PMID- 28511131
TI  - Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from
      central China.
AB  - To more fully understand the genetic diversity and molecular epidemiology of
      prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan
      province of China, 112 full-length ORF5 gene sequences, originating from Henan
      province between 2006 and 2015, were subjected to sequence variation and
      phylogenetic analysis. Phylogenetic analysis revealed that all Henan isolates
      belonged to the Type 2 genotype and could be further divided into three
      subgroups. Subgroup 1 and 2 viruses predominated in Henan and subgroup 2 overtook
      subgroup 1 as the most prevalent PRRSV between 2006 and 2015. Highly pathogenic
      PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine
      like isolates were observed in subgroup 3. Sequence variation analysis revealed
      that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1%
      amino acid sequence identity with each other. Primary neutralizing epitope (PNE)
      analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate,
      all but one of the subgroup 1 Henan isolates had mutations at amino acid 39
      within the key PNE of GP5. Analysis of the immunoreceptor tyrosine-based
      inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates
      had a highly conserved sequence between amino acids 77 and 82 positions of GP5. N
      linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5
      amino acid position 59 in two of the subgroup 2 Henan isolates. Another novel GP5
      amino acid mutation (44N->44D) was found in a single subgroup 1 Henan isolate
      (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV
      infectivity.

PMID- 28511132
TI  - Activity and in vivo dynamics of Bacillus subtilis DisA are affected by RadA/Sms
      and by Holliday junction-processing proteins.
AB  - Bacillus subtilis c-di-AMP synthase DisA and RecA-related RadA/Sms are involved
      in the repair of DNA damage in exponentially growing cells. We provide genetic
      evidence that DisA or RadA/Sms is epistatic to the branch migration translocase
      (BMT) RecG and the Holliday junction (HJ) resolvase RecU in response to DNA
      damage. We provide genetic evidence damage. Functional DisA-YFP formed dynamic
      foci in exponentially growing cells, which moved through the nucleoids at a speed
      compatible with a DNA-scanning mode. DisA formed more static structures in the
      absence of RecU or RecG than in wild type cells, while dynamic foci were still
      observed in cells lacking the BMT RuvAB. Purified DisA synthesizes c-di-AMP, but
      interaction with RadA/Sms or with HJ DNA decreases DisA-mediated c-di-AMP
      synthesis. RadA/Sms-YFP also formed dynamic foci in growing cells, but the foci
      moved throughout the cells rather than just on the nucleoids, and co-localized
      rarely with DisA-YFP foci, suggesting that RadA/Sms and DisA interact only
      transiently in unperturbed conditions. Our data suggest a model in which DisA
      moving along dsDNA indicates absence of DNA damage/replication stress via normal
      c-di-AMP levels, while interaction with HJ DNA/halted forks leads to reduced c-di
      AMP levels and an ensuing block in cell proliferation. RadA/Sms may be involved
      in modulating DisA activities.

PMID- 28511133
TI  - Phorate induced oxidative stress, DNA damage and differential expression of p53,
      apaf-1 and cat genes in fish, Channa punctatus (Bloch, 1793).
AB  - The present study was conducted to assess the in-vivo activities of certain
      molecular biomarkers under the impact of phorate exposure. Fish, Channa punctatus
      (35 +/- 3.0 g; 14.5 +/- 1.0 cm; Actinopterygii) were subjected to semi-static
      conditions having 5% (0.0375 mg/L for T1 group) and 10% of 96 h-LC50 (0.075 mg/L
      for T2 group) of phorate exposure for 15 and 30 d. The oxidative stress was
      assessed in terms of superoxide dismutase (SOD) and catalase (CAT) activities.
      DNA damage was measured as induction of micronuclei (MN) and consequent
      differential expression of apoptotic genes-tumor suppressor (p53), apoptotic
      peptidase activating factor-1 (apaf-1) and catalase (cat) in liver and kidney,
      two major sites of biotransformation in fish, were quantified. Our findings
      reveal significant (p < 0.001) augmentations in SOD and CAT activities of liver
      and kidney tissues. MN frequency in erythrocytes of fish also increases
      significantly (p < 0.05) in a dose- and time-dependent manner. The mRNA level of
      p53 increased significantly (p < 0.05) in liver at 10% of 96 h-LC50 of phorate
      exposure after 30 d suggesting generation of stress due to accumulation of
      reactive oxygen species (ROS). Eventually, these findings decipher the dual role
      of ROS in generating genotoxicity as is evident by micronuclei induction and
      differential regulation of p53, apaf-1 and cat genes during the phorate induced
      DNA damage and apoptosis in test fish. The experimental inferences drawn on the
      basis of activities of aforesaid biomarkers shall be helpful in elucidating the
      possible causes of apoptosis under stressful conditions. Further, this study
      finds ample application in biomonitoring of phorate polluted aquatic ecosystem.

PMID- 28511134
TI  - Cadmium toxicokinetics in the freshwater turtle, Chinemys reevesii.
AB  - This study was designed to investigate the toxicokinetics of Cadmium (Cd) in
      Chinemys reevesii. The animals were exposed to 15 mg/kg Cd chloride by
      intraperitoneal injection, and the Cd absorption, distribution, and excretion in
      different organs were determined. The results showed that Cd absorption reached
      its peak in the blood at 3 h after treatment. The accumulation of Cd was the
      highest in the liver and the second highest in the pancreas. All other tissues
      also accumulated Cd, such as spleen, kidney, intestine, lung, stomach, heart,
      brain, muscle. A small amount of Cd was found in the faeces. The urine and bile
      had low concentrations of Cd. In conclusion, absorbance of Cd reaches its peak at
      3 h in blood. The liver and pancreas are the major organs of Cd accumulation, and
      the major excretion route of Cd is through feaces.

PMID- 28511135
TI  - Solubility of organic compounds in octanol: Improved predictions based on the
      geometrical fragment approach.
AB  - Two new models are introduced to predict the solubility of chemicals in octanol
      (Soct), taking advantage of the extensive character of log(Soct) through a
      decomposition of molecules into so-called geometrical fragments (GF). They are
      extensively validated and their compliance with regulatory requirements is
      demonstrated. The first model requires just a molecular formula as input. Despite
      an extreme simplicity, it performs as well as an advanced random forest model
      involving 86 descriptors, with a root mean square error (RMSE) of 0.64 log units
      for an external test set of 100 molecules. For the second one, which requires the
      melting point Tm as input, introducing GF descriptors reduces the RMSE from about
      0.7 to <0.5 log units, a performance that could previously be obtained only
      through the use of Abraham descriptors. A script is provided for easy application
      of the models, taking into account the limits of their applicability domains.

PMID- 28511136
TI  - Fate of pharmaceuticals in soil after application of STPs products: Influence of
      physicochemical properties and modelling approach.
AB  - Depurated effluents can be employed as reclaimed water for irrigation in regions
      with low precipitations, while nutrients-rich biosolids are usually applied as
      fertilizer for agricultural purposes. However, both practices may result in the
      accumulation of micropollutants in the soil compartment, the contamination of
      groundwater, and/or their biotransfer to different living organisms until they
      finally may reach human receptors. The fate and transport of seven pharmaceutical
      and personal care products (PPCPs) with different physicochemical properties was
      analysed for these scenarios employing two different models: the buckets model
      and the HYDRUS-1D software package. The results indicated that these compounds
      have a low potential to contaminate groundwater in the type of soil under study
      (silty loam), although triclosan tended to accumulate in the top layers of the
      soil. Similar conclusions were reached through both models, although they
      predicted different solute plant uptake and accumulation patterns of the
      evaluated compounds. Therefore, the buckets model can be considered as an
      adequate option to perform a screening level assessment of these compounds.
      However, HYDRUS-1D could provide more information on the fate of pharmaceuticals
      in soil, thus contributing to reduce the uncertainty already associated to PPCPs.
      Additionally, the significant difference of the Hazard Index (HI) obtained from a
      human health risk assessment performed using the estimated soil concentrations
      from both models also contributed to recommend the use of a model that considers
      all the relevant mechanisms of mass transfer to reduce overestimation of risk.

PMID- 28511137
TI  - Effects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in
      developing zebrafish (Danio rerio).
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) which are widely used as pain
      relief medicines are causing increasing environmental concern due to their
      incomplete removal in wastewater treatment plant and potential toxicity on
      endocrine, kidney and reproduction in teleost fish. This study focused on the
      effects of widely used ibuprofen, diclofenac and paracetamol on the hatch and
      motor ability of early-stage zebrafish, by exposing embryos to the target
      chemicals at 5, 50 and 500 MUg/L starting from 6 h postfertilization (hpf). A
      significant reduction in hatch rate at 55 hpf was caused by both ibuprofen (-63%)
      and diclofenac (-58%) at 500 MUg/L. Exposure to high concentration of ibuprofen
      significantly decreased the spontaneous movement by 25%, and reduced the free
      swimming distance, duration and speed under dark condition by 41%, 29% and 30%,
      respectively. High concentration of diclofenac also caused 23% decrease in
      spontaneous movement, and reduced the swimming distance as well as active
      duration by 17% and 13% under light stimulation. In comparison, the exposure to
      paracetamol did not cause any notable effect. Among neuron related genes tested,
      the expression of neurog1 was down-regulated from ibuprofen and diclofenac
      exposure by 19% and 26%, while the expression of neurod1 was up-regulated only by
      ibuprofen (31%). These findings indicated that ibuprofen and diclofenac
      significantly affected embryo locomotivity and were potentially neurotoxic, thus
      posing threats to zebrafish development.

PMID- 28511138
TI  - Neurodevelopment for the first three years following prenatal mobile phone use,
      radio frequency radiation and lead exposure.
AB  - BACKGROUND: Studies examining prenatal exposure to mobile phone use and its
      effect on child neurodevelopment show different results, according to child's
      developmental stages. OBJECTIVES: To examine neurodevelopment in children up to
      36 months of age, following prenatal mobile phone use and radiofrequency
      radiation (RFR) exposure, in relation to prenatal lead exposure. METHODS: We
      analyzed 1198 mother-child pairs from a prospective cohort study (the Mothers and
      Children's Environmental Health Study). Questionnaires were provided to pregnant
      women at <=20 weeks of gestation to assess mobile phone call frequency and
      duration. A personal exposure meter (PEM) was used to measure RFR exposure for
      24h in 210 pregnant women. Maternal blood lead level (BLL) was measured during
      pregnancy. Child neurodevelopment was assessed using the Korean version of the
      Bayley Scales of Infant Development-Revised at 6, 12, 24, and 36 months of age.
      Logistic regression analysis applied to groups classified by trajectory analysis
      showing neurodevelopmental patterns over time. RESULTS: The psychomotor
      development index (PDI) and the mental development index (MDI) at 6, 12, 24, and
      36 months of age were not significantly associated with maternal mobile phone use
      during pregnancy. However, among children exposed to high maternal BLL in utero,
      there was a significantly increased risk of having a low PDI up to 36 months of
      age, in relation to an increasing average calling time (p-trend=0.008). There was
      also a risk of having decreasing MDI up to 36 months of age, in relation to an
      increasing average calling time or frequency during pregnancy (p-trend=0.05 and
      0.007 for time and frequency, respectively). There was no significant association
      between child neurodevelopment and prenatal RFR exposure measured by PEM in all
      subjects or in groups stratified by maternal BLL during pregnancy. CONCLUSIONS:
      We found no association between prenatal exposure to RFR and child
      neurodevelopment during the first three years of life; however, a potential
      combined effect of prenatal exposure to lead and mobile phone use was suggested.

PMID- 28511139
TI  - A successful transition to sulfonylurea treatment in male infant with neonatal
      diabetes caused by the novel abcc8 gene mutation and three years follow-up.
AB  - Neonatal diabetes mellitus is a rare monogenic disease with incidence of 1/90,000
      newborns. A case of two months aged male infant with life threatening diabetic
      ketoacidosis is presented with novel ABCC8 gene mutation (p.F577L), successful
      transition from insulin to sulfonylurea and follow-up of three years.

PMID- 28511140
TI  - Different impacts of acylated and non-acylated long-acting insulin analogs on
      neural functions in vitro and in vivo.
AB  - AIMS: Centrally administered insulin improves cognitive functions in patients
      with Alzheimer's disease; however, it remains unknown whether long-acting insulin
      analogs exert more pronounced effects than insulin. In the present study, we
      directly compared the effects of insulin and its analogs on neural functions in
      vitro and in vivo. METHODS: Cultured rat cerebral cortical neurons were treated
      with insulin, insulin glargine U100 (Gla), insulin detemir (Det), or insulin
      degludec (Deg). Moreover, these drugs were intracerebroventricularly administered
      to mice. Their efficacies were evaluated by biochemical and behavioral analyses.
      RESULTS: In cultured neurons, insulin, Gla, and Det increased phosphorylation of
      Akt and enhanced gene expression of brain-derived neurotrophic factor to a
      similar extent, although Deg was less effective. The effects of Det and Deg, but
      not insulin and Gla were suppressed by addition of albumin. When the drug was
      centrally administered, the increasing effects of insulin on the Akt
      phosphorylation were comparable to those of Gla but greater than those of Det in
      hippocampus and cerebral cortex of diabetic db/db and non-diabetic db/m+ mice.
      Moreover, insulin and Gla enhanced memory functions in Y-maze test and suppressed
      depression-like behavior in forced swim test in normal mice to a similar extent,
      and these effects were more potent than those of Det. CONCLUSIONS: Insulin and
      Gla have greater impacts on central nervous system than insulin analogs with high
      albumin sensitivity, such as Det and Deg. These pharmacological profiles should
      be taken into account for developing an insulin-based therapy to treat
      Alzheimer's disease.

PMID- 28511141
TI  - The co-occurrence of depressive symptoms and cognitive impairment and its
      relationship with self-care behaviors among community dwelling older adults with
      diabetes.
AB  - AIMS: The aims of the present study were to investigate the co-occurrence of
      depressive symptoms and cognitive impairment in community dwelling older adults
      with diabetes and its relationship with specific diabetes self-care behaviors.
      METHODS: We analyzed data from two national samples of older adults (65years or
      older) with self-reported physician-diagnosed diabetes (N=1034), who participated
      in the 2005 or 2009 National Health Interview Survey in Taiwan. The Mini-Mental
      State Examination was used to assess cognitive function. The Center for
      Epidemiologic Studies Depression Scale was used to assess depressive symptoms.
      The study assessed self-care behaviors including medication adherence, exercise,
      healthy diet, and self-monitoring of blood glucose. RESULTS: In this study, 8.8%
      of participants with diabetes had both depressive symptoms and cognitive
      impairment. After adjusting for other factors, participants with both cognitive
      impairment and depressive symptoms were less likely to exercise (Prevalence
      Ratios (PR)=0.66; 95% Confidence Intervals (CI)=[0.47-0.91]; P-value=0.011), and
      have a healthy diet (PR=0.82; 95%CI=[0.70-0.96]; P-value=0.012). CONCLUSIONS: Our
      results illustrate the high prevalence of combined depressive symptoms and
      cognitive impairment and that this combination is associated with worse self-care
      behaviors in older adults with diabetes. These findings highlight the difficulty
      that some older adults with diabetes may have in maintaining self-care behaviors
      in the presence of depressed mood and cognitive impairment, particularly in the
      areas of diet and exercise. The results emphasize the importance of providing
      more support for these aspects of self-care to such older adults.

PMID- 28511143
TI  - DNA-assisted upconversion nanoplatform for imaging-guided synergistic therapy and
      laser-switchable drug detoxification.
AB  - The side effects of chemotherapy bring significant physical and psychological
      suffering to patients. To solve this urgent medical problem, Yb3+ and Er3+ co
      doped NaLuF4 upconversion nanoparticles (UCNPs) were constructed for upconversion
      luminescence (UCL)-labeled diagnosis under 980 nm laser irradiation. The UCNPs
      were then modified layer by layer with polypyrrole and a special programming DNA
      segment as photothermal conversion agents and controllable drug carriers,
      respectively. The nanoplatform was successfully used for imaging-guided
      synergistic therapy (photothermal therapy and chemotherapy) at a safe power
      density (300 mW cm-2), and DNA-assisted detoxification at lower temperature in
      cancer cells when the laser off. The synergistic therapy of the nanoplatform
      achieved a higher therapeutic index (~85%) than chemotherapy only (~44%) and
      photothermal therapy only (~25%) in vitro. In vivo experiments also suggested
      that the nanoplatform had a higher therapeutic effect and lower side effects. The
      toxicity study was also evaluated, indicating the nanoplatform is low toxic to
      living system. This multifunctional upconversion nanoplatform provided an
      innovative method for imaging-guided photothermal-chemotherapy and laser
      switchable drug detoxification.

PMID- 28511142
TI  - Tailoring nanostructured lipid carriers for the delivery of protein antigens:
      Physicochemical properties versus immunogenicity studies.
AB  - New vaccine formulations are still highly anticipated in the near-future to face
      incoming health challenges, such as emergence or reemergence of severe infectious
      diseases, immunosenescence associated with elderly or the spread of pathogens
      resistant to antibiotics. In particular, new nanoparticle-based adjuvants are
      promising for sub-unit vaccines in order to elicit potent and long lasting immune
      responses with a better control on their safety. In this context, an innovative
      delivery system of protein antigens has been designed based on the chemical
      grafting of the antigen onto the shell of Nanostructured Lipid Carriers (NLC). By
      using the well-known ovalbumin (OVA) as model of protein antigen, we have
      compared the immunogenicity properties in mice of different formulations of NLC
      grafted with OVA, by studying the influence of two main parameters: the size (80
      nm versus 120 nm) and the surface charge (anionic versus cationic). We have shown
      that all mice immunized with OVA delivered through NLC produced much higher
      antibody titers for all tested formulations as compared to that immunized with
      OVA or OVA formulated in Complete Freund Adjuvant (CFA, positive control). More
      interestingly, the 80 nm anionic lipid particles were the most efficient antigen
      carrier for eliciting higher humoral immune response, as well as cellular immune
      response characterized by a strong secretion of gamma interferon (IFN-gamma).
      These results associated with the demonstrated non-immunogenicity of the NLC
      carrier by itself open new avenues for the design of smart sub-unit vaccines
      containing properly engineered lipid nanoparticles which could stimulate or
      orient the immune system in a specific way.

PMID- 28511144
TI  - Development of a prognostic scale for severely hemiplegic stroke patients in a
      rehabilitation hospital.
AB  - OBJECTIVES: For patients with severe hemiplegia in a rehabilitation hospital,
      early prediction of the functional prognosis and outcomes is challenging. The
      purpose of this study was to create and verify a prognostic scale in severely
      hemiplegic stroke patients and allowing for prediction of (1) the ability to walk
      at the time of hospital discharge, (2) the ability to carry out activities of
      daily living (ADL), and (3) feasibility of home discharge. PATIENTS AND METHODS:
      The study was conducted on 80 severely hemiplegic stroke patients. A prognostic
      scale was created as an analysis method using the following items: mini-mental
      state examination (MMSE) at the time of admission, modified NIH stroke scale (m
      NIHSS); trunk control test (TCT); and the ratio of the knee extensor strength on
      the non-paralyzed side to the body weight (KES/BW-US). We verified the
      reliability and validity of this scale. RESULTS: We established a prognostic
      scale using the MMSE, m-NIHSS, TCT, and KES/BW-US. A score of 56.8 or higher on
      the prognostic scale suggested that the patient would be able to walk and that
      assistance with ADL would be unnecessary at the time of hospital discharge. In
      addition, a score of 41.3 points indicated that the patient's return home was
      feasible. The reliability and the results were in good agreement. These findings
      showed that the ability or inability to walk was predictable in 85%, the need of
      assistance with ADL in 82.5%, and the feasibility of home return in 76.3% of
      cases. CONCLUSION: At the time of admission, four evaluation items permitted the
      prediction of three outcomes at time of discharge. Our formula predicts three
      outcomes with an accuracy of more than 76%.

PMID- 28511145
TI  - Plasma membrane repair: the adaptable cell life-insurance.
AB  - The plasma membrane is the most basic element necessary for the cell to exist and
      be distinguishable from its environment. Regulated mechanisms allow tightly
      controlled communication between intacellular and extracellular medium allowing
      the maintenance of a specific biochemical environment, optimized for cellular
      functions. The anarchic and uncontrolled opening of a hole in the PM induces a
      change in the concentration of ions and oxidizing agents perturbing homeostasis.
      Fortunately, the cell possesses mechanisms that are capable of reacting to sudden
      extracellular medium entry and to block the leakage locally. Here we summarize
      the known mechanisms of membrane repair and how the size of the wound and the
      resulting calcium entry activates preferentially one or another mechanism adapted
      to the magnitude of the injury.

PMID- 28511146
TI  - Real world prospective experience of axitinib in metastatic renal cell carcinoma
      in a large comprehensive cancer centre.
AB  - BACKGROUND: Axitinib has shown activity in metastatic renal cell carcinoma (mRCC)
      in a large phase III clinical trial and was approved in patients who failed first
      line therapy. This drug has been available in France since November 2012. The
      objective is to report efficacy and safety of axitinib in mRCC outside of
      clinical trials. METHODS: A prospective evaluation of mRCC patients treated by
      axitinib in second or further next-line therapy at Gustave Roussy was conducted
      from 2012 to 2015. Objective response rate (ORR), progression-free survival
      (PFS), time to treatment failure (TTF), overall survival (OS) and toxicities were
      analysed. The correlation between clinical markers and ORR, PFS, TTF and OS were
      explored. RESULTS: One-hundred and sixty patients with mRCC, received axitinib in
      second (40%) or further next-line therapy (60%). International Metastatic Renal
      Cell Carcinoma Database Consortium (IMDC) risk group classification was good,
      intermediate and poor in 13%, 54% and 32%, respectively. Dose titration (DT) to 7
      mg twice a day (bid) was performed in 38% and to 10 mg bid in 19% of the
      patients. Hypertension was the most common adverse event, (grade (G)3: 39%; G4:
      2%). ORR occurred in 32% (n = 33, only partial response). Median PFS, TTF and OS
      were 8.3, 5.8 and 16.4 months, respectively. IMDC risk group and DT at 2 weeks
      are associated to ORR while grade 3 hypertension is marginally associated. IMDC
      risk group and grade 3 hypertension are significantly associated with better PFS,
      TTF and OS while DT at 2 weeks is associated to PFS and TTF. CONCLUSION: Efficacy
      of axitinib in routine practice is similar to that previously reported, not only
      in second- but also in further next-lines of therapy.

PMID- 28511147
TI  - Squamous cell carcinoma of the pancreas: A systematic review and pooled survival
      analysis.
AB  - The diagnosis and treatment of squamous cell carcinoma of the pancreas pose
      dilemmas in the clinical practice. The present study was performed according to
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. Eligible articles were sought in MEDLINE up to 30th April 2016. A
      pooled Cox regression analysis was performed to evaluate factors potentially
      associated with overall survival (OS) and relapse-free survival (RFS). Fifty-four
      cases of pure squamous cell pancreatic carcinomas were identified in total. The
      mean age was 61.9 years, and most patients were males (61.1%). The median OS was
      7 months. Resectability (p = 0.003) and more recent publication year (p < 0.001)
      were associated with better OS, as was low/intermediate tumour grade (p = 0.032)
      with RFS. Despite its poor prognosis, survival rates of pancreatic squamous cell
      carcinoma seem improved during the recent years; resectability and
      low/intermediate grade emerged as favourable prognostic factors. Collaborative
      epidemiological studies are deemed necessary to further validate the results
      stemming from the published case reports of this rare entity.

PMID- 28511148
TI  - Computational studies of membrane proteins: from sequence to structure to
      simulation.
AB  - In this review, I discuss the recent advances in computational approaches to
      studying membrane protein structures, covering the latest methods for predicting
      a protein structure from its amino acid sequence, through to methods for
      assessing the structural dynamics and lipid interactions within molecular
      simulations of complex biological membranes. These approaches have not only
      benefited from advances in the computational software and architectures, but have
      also been assisted by a prodigious rise in the number of both the molecular
      sequences and experimentally determined membrane protein structures. The former,
      in part stimulated by metagenomics sequencing techniques, has led to an increased
      prediction accuracy for the computationally folded protein structures. The
      latter, assisted by improvements in structural biology approaches, has led to
      longer, larger and more complex molecular simulations of membrane proteins; many
      of which have greater relevance to human disease. Here I describe the methods for
      predicting a membrane protein structure from sequence, discuss the approaches to
      configure membrane protein simulations and detail the techniques used to identify
      and characterize specific lipid binding sites to membrane protein structures.

PMID- 28511149
TI  - Analysis of extracellular brain chemistry during percutaneous dilational
      tracheostomy: A retrospective study of 19 patients.
AB  - OBJECTIVE: The purpose of this study was to analyze changes in brain tissue
      chemistry around percutaneous dilational tracheostomy (PDT) in patients with
      acute brain injury (ABI) in a retrospective single-center analysis. PATIENTS AND
      METHODS: We included 19 patients who had continuous monitoring of brain tissue
      chemistry and intracranial pressure (ICP) during a 20h period before and after
      PDT. Different microdialysis parameters (lactate, pyruvate, lactate pyruvate
      ratio (LPR), glycerol and glutamate) and values of ICP, cerebral perfusion
      pressure (CPP) and brain tissue oxygenation (PBrO2) were recorded per hour. Mean
      values were compared between a 10h period before PDT (prePDT) and after PDT
      (postPDT). RESULTS: Mean values of cerebral lactate, pyruvate, LPR, glycerol and
      glutamate did not differ significantly between prePDT and postPDT. In addition,
      the rate of patients, which exceeded the known threshold was similar between
      prePDT and postPDT. Only one patient showed a strong increase of cerebral
      glycerol during the postPDT period, but analysis of subcutaneous glycerol could
      exclude an intracerebral event. ICP, CPP and PBrO2 did not exhibit significant
      changes. CONCLUSIONS: We could exclude the occurrence of cerebral metabolic
      crisis and the excess release of cerebral glutamate and glycerol in a series of
      19 patients. Our results support the safety of PDT in patients with ABI.

PMID- 28511150
TI  - Disparities in cancer stage at diagnosis and survival of Aboriginal and non
      Aboriginal South Australians.
AB  - BACKGROUND/AIM: This study tested the utility of retrospectively staging cancer
      registry data for comparing stage and stage-specific survivals of Aboriginal and
      non-Aboriginal people. Differences by area level factors were also explored.
      METHODS: This test dataset comprised 950 Aboriginal cases and all other cases
      recorded on the South Australian cancer registry with a 1977-2010 diagnosis. A
      sub-set of 777 Aboriginal cases diagnosed in 1990-2010 were matched with randomly
      selected non-Aboriginal cases by year of birth, diagnostic year, sex, and primary
      site of cancer. Competing risk regression summarised associations of Aboriginal
      status, stage, and geographic attributes with risk of cancer death. RESULTS:
      Aboriginal cases were 10 years younger at diagnosis, more likely to present in
      recent diagnostic years, to be resident of remote areas, and have primary cancer
      sites of head & neck, lung, liver and cervix. Risk of cancer death was associated
      in the matched analysis with more advanced stage at diagnosis. More Aboriginal
      than non-Aboriginal cases had distant metastases at diagnosis (31.3% vs 22.0,
      p<0.001). After adjusting for stage, remote-living Aboriginal residents had
      higher risks of cancer death than Aboriginal residents of metropolitan areas. Non
      Aboriginal cases had the lowest risk of cancer death. CONCLUSION: Retrospective
      staging proved to be feasible using registry data. Results indicated more
      advanced stages for Aboriginal than matched non-Aboriginal cases. Aboriginal
      people had higher risks of cancer death, which persisted after adjusting for
      stage, and applied irrespective of remoteness of residence, with highest risk of
      death occurring among Aboriginal people from remote areas.

PMID- 28511151
TI  - Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.
AB  - INTRODUCTION: To provide long-term vascular access in clinical oncology
      peripheral forearm veins (up to 95% of patients in Ukraine), central venous
      access and "complete implanted vascular systems" are used most often. Many
      oncology patients have contraindications to catheterization of superior vena
      cava. Besides, exploitation of central veins is associated with potential
      technical and infectious complications. The aim - to study short-term and long
      term results of arteriovenous fistula exploitation as vascular access for
      continuous anticancer therapy. MATERIALS AND METHODS: Peripheral venous bed
      status in 41 oncology patients taking long-term chemotherapy treatment is
      analyzed in the article. Doppler sonography, morphologic and immune histochemical
      analyses were used in the study. RESULTS: Doppler sonography found qualitative
      and quantitative changes in forearm veins at different time periods after
      initiation of chemotherapy in the majority of patients. The major morphologic
      manifestations of venous wall damage were chemical phlebitis, local or extended
      hardening of venous wall, venous thrombosis and extravasations with necrosis and
      subsequent paravasal tissue sclerosis. Alternative vascular access created in 12
      patients completely met the adequacy criteria (safety, multiple use, longevity,
      realization of the designed therapy program). The conclusion was made about
      inapplicability of forearm veins for long-term administration of cytostatic
      agents. If it is impossible to use central veins, arteriovenous fistula can
      become an alternative vascular access.

PMID- 28511153
TI  - [Morbidity rate of obesity in children in ukraine. Overweight as noncontagious
      disease risk factor].
AB  - INTRODUCTION: The upsurge of prevalence rate of obesity and overweight that in
      the majority of cases traces back to childhood is a risk factor of the most
      common noncontagious diseases in adults. THE AIM: The aim was to analyze
      prevalence of obesity in children in Ukraine and to conduct the pilot study of
      medical condition of overweight children. MATERIALS AND METHODS: Official state
      statistics of prevalence rate of obesity in kids and screening data of
      anthropometric characteristics, arterial tension levels, physical performance
      decrement and medical condition of children (boys - 50, girls - 90, average age -
      15,1+/-0,1 years) was used in research. Data calculation performed by Statistica
      v. 6.0 software. RESULTS: Over the past few decades, the morbidity rate of
      obesity in children in Ukraine has greatly increased, especially in year class 15
      17. Insufficient diagnosis of obesity in children is the consequence of the
      inadequacy of the existing system of preventive care and monitoring survey of
      decease risk factors. Children with body mass index (BMI) above normal have a
      risk of work decrement in 5,2 times (odds ratio, OR=5,2, CI95%: 1,7-10,6). Such
      children have higher risk of development of the diseases of the respiratory
      system (OR=8,1; CI95%: 3,9-13,6) and allergic dermatitis (OR=7,7; CI95%: 3,7
      12,9). The odds ratio of arterial hypertension in such children is equal to
      3,46+/-0,3 (95%CI: 2,0-5,9). CONCLUSIONS: According to prediction calculations,
      the situation with the increase of prevalence rate of obesity in children in
      Ukraine is unfavorable. The introduction of measures aimed at finding children
      with obesity, their registration and monitoring of patients' health with due
      regard to decease risk factors at the primary care level would conduce to
      improving prevention of obesity and prevention of alimentary diseases
      progression.

PMID- 28511154
TI  - Cutaneous squamous cell carcinoma: epidemiological aspects among the population
      of Ukraine.
AB  - INTRODUCTION: In the structure of malignant skin neoplasms, the tumours of
      epithelial origin take the first place, among them the prevalence of cutaneous
      squamous cell carcinoma (cSCC) is about 20%. The aim of the work involves the
      analysis of cSCC epidemiological features among the contingent of the State
      Scientific Institution "Scientific and Practical Centre of Preventive and
      Clinical Medicine" of the State Administration (SIS) over 2005-2014 (Ukraine,
      Kyiv). MATERIAL AND METHODS: For retrospective epidemiological analysis there was
      used identifying information of patients with cSCC of the contingent of SIS over
      2005-2014 in comparison with the data on patients with cSCC of Kyiv city and Kyiv
      region over the same period of time. RESULTS: The morbidity rate of cSCC among
      the contingent of SIS in 2005-2014 increased from 6.7 per 100,000people to 37.1
      per 100,000 people. Among men it increased from 8.2 per 100,000 people to 59.2
      per 100,000 people, and among women - from 6.6 per 100,000 people to 19.2 per
      100,000people. Among the contingent of SIS the highest incidence both in men and
      women was observed in the age group of 85 and upwards; among men it was 115.2 per
      100,000 people, and among women - 112.0 per 100,000 people. CONCLUSIONS: The
      morbidity rate of cSCC among the contingent of SIS in 2005-2014 was significantly
      higher (p<0.05) than the morbidity rate among the population of Kyiv city and
      Kyiv region over the same period of time, with the prevalence of patients aged 85
      and upwards, both men and women.

PMID- 28511152
TI  - [Pathogenetic substantiation of complex treatment of nonalcoholic steatohepatitis
      and steatosis in patients with pre-diabetes and type 2 diabetes].
AB  - INTRODUCTION: Thesis is devoted to the optimization of complex treatment of
      nonalcoholic steatohepatitis and steatosis in patients with pre-diabetes and type
      2 diabetes by acting on carbohydrate and lipid metabolism as well as providing
      hepatoprotection. AIM: Optimization of diagnostics and treatment in patients
      treatment of nonalcoholic steatohepatitis and steatosis in patients with pre
      diabetes and type 2 diabetes. MATERIAL AND METHODS: Examination and treatment of
      117 patients with NAFLD and pre-diabetes and type 2 diabetes was performed.
      RESULTS: It has been proved that the use of a therapeutic scheme that includes a
      balanced diet, taking into account the daily requirement in proteins, fats and
      carbohydrates, daily 30-minute walks at a brisk pace, rosuvastatin 10 mg/d, omega
      3 PUFA 1000 mg/d and ursodeoxycholic acid 10 mg/kg/d in patients with NAFLD and
      pre-diabetes facilitates regression of signs of steatosis. In patients with NAFLD
      and type 2 diabetes the above mentioned therapeutic scheme including sitagliptin
      100 mg/d promotes regression of steatohepatitis in steatosis. CONCLUSIONS: The
      prevalence of nonalcoholic steatohepatitis and liver steatosis in patients with
      pre-diabetes has been studied. It has been proved that patients with NAFLD and
      pre-diabetes belong to the group with high cardiovascular risk. The features of
      metabolic disorders in patients with nonalcoholic fatty liver disease and pre
      diabetes or type 2 diabetes were researched. Differentiated treatment schemes of
      nonalcoholic steatosis and steatohepatitis in patients with pre-diabetes and type
      2 diabetes have been approved for use.

PMID- 28511155
TI  - [The role of inflammatory biomarkers in cardiovascular risk stratification].
AB  - INTRODUCTION: The increase in cardiovascular diseases requires the search for
      ways to predict complications based on research additional to traditional risk
      factors, conduct a study of the formation mechanisms of these complications and
      to design new treatment strategies. AIM: To get an idea about the relationship
      between inflammation in the blood vessels, atherosclerosis and cardiovascular
      consequences based on the study of the role of biomarkers of inflammation.
      MATERIAL AND METHODS: the literature on the estimation of risk development of
      cardiovascular diseases based on the study of the role of biomarkers of vascular
      inflammation; bibliographic, a systematic approach. RESULTS: Algorithm
      stratification of cardiovascular risk includes a review of the traditional risk
      factors for the purpose of preventive therapy. A large number of cases of
      cardiovascular events (myocardial infarction, stroke) occurs in bessimptomnom
      patients with normal lipid. The use of additional risk factors for development of
      cerebral and cardiac disorders will allow to foresee the consequences and to
      prevent mortality from cardiovascular disease. Study of the role of inflammation
      in development of cardiovascular diseases allows the use of SB and PL-FLA2 as an
      important additional cardiovascular markers, independent of traditional risk
      factors. CONCLUSIONS: The use of biomarkers LP-FLA2 and SB specific to vascular
      inflammation, allows to establish the relationship between endovascular
      inflammation, atherosclerosis development and progression of cardiovascular
      diseases and to prevent cerebral and cardiac disorders in patients with
      traditional risk factor .

PMID- 28511156
TI  - The role of the persistent enterovirus infection in development of acute stroke.
AB  - INTRODUCTION: The role of enteroviruses in development of dilated cardiomyopathy,
      myocardial infarction, myocarditis, pericarditis is known. THE AIM: To examine
      the role of chronic enterovirus infections in development of acute stroke.
      MATERIAL AND METHODS: Blood samples from 72 patients with acute stroke (study
      group) and 35 patients without vascular disease (control group) were investigated
      by reverse transcription polymerase chain reaction for the presence of
      enterovirus RNA, by using virological method to detect enteroviruses, by ELISA
      for the levels of IgM and IgG antibodies to enteroviruses. RESULTS: The
      enteroviruses genomes were detected significantly often in the serum of patients
      with stroke (23,6 +/- 5,9%) than in control group (2,9 +/- 2,8%). The viruses
      were isolated and were identified as Coxsackie B (serotypes 2, 3, 4) and ECHO
      (serotypes 6, 9, 27 (two strains), 29), three strains have not been identified in
      study group. IgM to enteroviruses were not found in the sera of both groups of
      patients. IgG to enteroviruses were detected in 17 patients in study group (23,6
      +/- 5,9%) and 2 patients in control group (5,7 +/- 3,9%). The presence of
      enteroviruses genomes and IgG in sera of patients in control group (11,1 +/-
      3,7%) indicate the persistence of enteroviruses. The proportion of patients with
      IgG to enteroviruses in sera is higher in study group (12,5 +/- 3,9%) than in
      control group (5,7 +/- 3,9%). CONCLUSION: The enterovirus infections play trigger
      role in development of acute stroke.

PMID- 28511157
TI  - [Conceptual approaches to improve the system of preventive medical examinations
      of the adult population].
AB  - INTRODUCTION: Health indicators Ukraine's adult population over the last decade
      still too high for both countries of the European Community. Features direction
      of preventive health system of Ukraine, currently used extremely limited.
      Existing approaches to planning and carrying out preventive medical examinations
      in our country are outdated and are formal, so improving the existing system of
      preventive medical examinations of the adult population is necessary and timely.
      AIM: To prove scientifically conceptual approaches to improving the planning and
      implementation of preventive medical examinations of adults through functional
      and structural changes. MATERIALS AND METHODS: Literature review, system analysis
      and conceptual modeling method. RESULTS: The analysis of the experience of our
      country for the prevention of the most common diseases and the state of the
      resource base for its conduct theoretically grounded and presented, functional
      structural model of preventive medical examinations of the adult population,
      based on are: phasing of checkups, the introduction of sex and age of maps,
      determination at increased risk of diseases and the establishment / improvement
      of the automated monitoring systems of risk factors for noncommunicable diseases.
      CONCLUSIONS: Carrying out preventive medical examinations of the adult population
      using gender and age card allows you to choose the most appropriate preventive
      measures and to pay particular attention to preventive measures aimed at
      preventing the leading causes of disease and disability in a particular age
      group.

PMID- 28511158
TI  - Evolution of some indicators of systemic immunity in patients with acne while
      using laser therapy.
AB  - INTRODUCTION: One of the important problems in modern dermatology is to improve
      treatment efficiency of acne being a common cause for cicatricial skin changes,
      loss of performance capability and social activity and negatively affects the
      psycho-emotional state of patients and their quality of life. The topicality of
      the disease is due to the high degree of its proliferation, chronic and recurrent
      course, and resistance to existing therapies. Reducing the effectiveness of skin
      diseases treatment, including that of acne, at present, is associated with
      developing resistance to drugs, which causes the use of non-drug methods in
      dermatology nowadays, including low-intensity laser therapy. Objective - to
      determine evolution of the systemic immunity indices in patients with acne with
      different degrees of severity in the course of a standard and comprehensive
      treatment by laser therapy. MATERIALS AND METHODS: We observed 77 patients with
      acne aged 18-25 years; 32 of them received standard therapy, other 45 patients
      were additionally prescribed combined (superficial venous and external) laser
      therapy. We determined the indices of all patients' systemic immunity using well
      known techniques. RESULTS: It has been established, that using laser therapy in
      comprehensive treatment of patients with acne promotes the normalization or a
      tendency to normalization of the systemic immunity and phagocytosis with
      significant difference between the indices of the individuals who received a
      standard therapy alone.

PMID- 28511159
TI  - Effect of apple polyphenol concentrate on lipid metabolism in rats under
      experimental insulin resistance.
AB  - INTRODUCTION: Obesity is strongly associated with an increased risk of developing
      insulin resistance as the metabolic indicator of prediabetes and a major risk
      factor in diabetes mellitus type 2 pathogenesis. Medicinal products obtained from
      apples can be used as potent prophylactic and therapeutic remedies in treatment
      of diabetes mellitus. AIM: Experiment was designed to study the effect of total
      apple polyphenol food concentrate on lipid metabolism under experimental IR.
      MATERIALS AND METHODS: Male Wistar rats weighting 180-210 g were used in the
      experiment. IR was induced by high-calorie diet enriched with fructose. The
      effect of total apple polyphenol food concentrate was compared with the action of
      epigallocatechin gallate and quercetin. To estimate the alterations in lipid
      metabolism in liver homogenate were measured triacylglycerols, free fatty acids,
      total phospholipids, TBA-reactive substance and conjugated dienes contents. In
      blood serum were measured total lipids, triacylglycerols, cholesterol, total
      phospholipids and reduced glutathione levels. RESULTS: The obtained results
      indicated that feeding rats with high-calorie diet enriched with fructose caused
      the dyslipidemia and oxidative stress development. The administration of
      quercetin, epigallocatechin gallate and total apple polyphenol food concentrate
      improved disorders of lipid metabolism and pro-oxidant-antioxidant homeostasis.
      CONCLUSIONS: Total apple polyphenol food concentrate had a more pronounced effect
      on studied indices that is probably due to synergism and additive effect of
      extract numerous components.

PMID- 28511160
TI  - Features of some clinical examination parameters in patients with psoriatic
      arthritis.
AB  - INTRODUCTION: The relationship of cause-and-effect mechanisms of exacerbation and
      progressing with defining of the role of stress reaction in the psoriatic
      arthritis (PA) development has been examined in the article by analyzing the
      characteristics of medical history, current dynamics as well as clinical,
      instrumental and laboratory examinations. The objective was to study the role of
      basic indices of laboratory examinations of patients used clarify their role in
      the pathogenesis of PA. MATERIALS AND METHODS: The concentration of trigger
      cytokines - IL-1beta, IL-8, IL-17, IL-22, stress hormones - ACTH and cortisol,
      state of cell-antibody mediated immunity (CD3+, CD4+, CD8+, CD16+, CD22+, IRI,
      IgM, IgG levels) in the serum of patients were defined. RESULTS AND DISCUSSION:
      We have detected the possible changes of stress-reaction mediator concentrations
      in the serum of patients with PA (i.e. decreasing of the status of cell immunity
      indices (CD3+, CD4+, CD8+ T- lymphocytes, V- lymphocytes CD22+ fraction, IRI with
      compensatory increasing of the levels of CD16+ T-cells, cytokines - IL-1 beta, IL
      8, IL-17, IL-22, stress hormone - cortisol, immunoglobulins IgM, IgG, CIC)
      irrespective of the disease duration which testifies the strain of their stress
      realising mechanisms, even if clinical stabilization of skin and joint process is
      normalized. CONCLUSIONS: Thus, the final diagnosis of PA is determined only under
      aggregation of anamnestic, clinical, instrumental and laboratory data and the
      results of additional examinations. The indices mentioned above are key mediators
      of stress-realizing immune-neuroendocrine system and play an ambiguous role in
      the development of PA, their various effects require further study.

PMID- 28511161
TI  - [The diagnostics and clinical pattern of nonalcoholic fatty liver disease in
      patients with pre-diabetes and type 2 diabetes and obesity].
AB  - INTRODUCTION: The data of epidemiological researches confirm the tendency in
      increasing of non alcoholic fatty liver disease (NAFLD) in patients with insulin
      resistance which occurs because of obesity, diabetes type 2 and metabolic
      syndrome. AIM: Optimization of diagnostic and treatment efficacy in patients with
      non alcoholic steatosis and steatohepatitis on the background of obesity.
      MATERIALS AND METHODS: General clinical examination of patients, laboratory and
      instrumental methods ( fatty liver index, non invasive assessment of liver,
      morphology, electrocardiography, treadmillergometry, ultrasound examination of
      abdominal organs, liver elastography,CT,MRI, methods of statistical analysis.
      RESULTS: NAFLD was diagnosed in 98.4% of patients with diabetes type 2, from
      which steatosis was found in 54.84% and steatohepatitis in 45.16%. In individuals
      with prediabetes NAFLD was in 70.5%, of which 85.45% with steatosis and 14.55%
      steatohepatitis (p<0.05). The clinical picture of patients with NAFLD prevailed
      such symptoms and complaints: flatulence in 43.59% of patients, weakness and pain
      in the right upper quadrant in 29.9% of patients. Fewer patients complained on
      discomfort in abdomen 28.21%, constipation 21.37% and feeling of bitterness in
      the mouth 21.37%. CONCLUSION: Clinical features of NAFLD are polysymptomatic.
      There are prevalence of dyspeptic syndromes (bloating met in 43.59% of patients,
      pain in right upper quadrant and discomfort in abdomen -29.91%, constipation-
      28.21%, bitterness in mouth-21.37%. Determination of fatty liver index is very
      informative method of screening patients with hepatisteatosis.

PMID- 28511162
TI  - Improvement of the complex medical treatment for the patients with chronic
      biliary pancreatitis.
AB  - INTRODUCTION: The most common reason of chronic pancreatitis is liver and bile
      ducts disease: functional disorders, chronic cholecystitis, cholelithiasis and
      cholecystectomy in medical history. All these changes are associated with the
      colloidal structure of bile, increased lithogenicity, gallstones formation,
      Oddi's sphincter dysfunction, dysmotility and inflammation in the bile ducts. THE
      AIM: to study the effectiveness of using medicine Liveria IC (metadoxine) in
      standard therapy as well as effect on spectrum of blood serum lipids and
      structural condition of liver (stiffness) and pancreas in patients with chronic
      biliary pancreatitis combined with obesity. MATERIALS AND METHOD: 115 patients
      suffering from chronic biliary pancreatitis and obesity were the subjects of the
      study. They were compared to etiological factor socioeconomic conditions and
      nutrition (regular food 5 times a day without aggressive food (fatty, spicy,
      sour, fried products)). Also the effect of the alcohol factor was excluded.
      RESULTS: The obtained decrease in stiffness of the liver and pancreas indicates
      an improvement of their structural state. CONCLUSIONS: Using medication LiveriaIC
      (metadoxine) as the part of the complex therapy for the patients who are
      suffering from CBP combined with obesity gives some improvement of the lipid
      profile indices and the structural condition of liver and pancreas (according to
      the data of SWE) (r<0.05).

PMID- 28511163
TI  - [Impact of physical activity on anthropometric indices in patients with
      nonalcoholic fatty liver disease and pre-diabetes or type 2 diabetes].
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is currently the most
      common cause of chronic liver disease in many developed countries. The first
      step, which is offered to all patients with NAFLD includes lifestyle
      modifications, low-calorie diet, increased physical activity and giving up
      smoking. OBJECTIVE: to evaluate the efficiency of the daily 30-minute walking at
      a fast pace on the dynamics of anthropometric indices in patients with NAFLD and
      pre-diabetes or type 2 diabetes. MATERIALS AND METHODS: The study included 59
      patients with nonalcoholic fatty liver disease and impaired carbohydrate
      metabolism, which conducted a comprehensive clinical examination that included
      collection of anthropometric data, physical examination and taking venous blood
      for laboratory analysis, ultrasound of the abdomen. RESULTS: According to
      statistical analysis, patients on the background of NAFLD and pre-diabeetes /
      type 2 diabetes, performing daily 30-minute walks at a fast pace, found
      significant changes of anthropometric indices. CONCLUSIONS: Daily 30-minute
      walking at a fast pace is an effective method on reduction of body weight in
      patients with NAFLD and pre-diabetes or type 2 diabetes.

PMID- 28511164
TI  - Changes of lipidic and the immunological state at patients with a metabolic
      syndrome in Ukraine.
AB  - INTRODUCTION: The metabolic syndrome has become pandemic nature and tends to
      rejuvenation in the world. Elucidation of the pathogenic mechanisms on membrane
      cell level will optimize the treatment of patients with metabolic syndrome and
      prevention of metabolic syndrome on the level of pre-clinical manifestations.
      AIM: to study the immunological status and lipid metabolism in the patients with
      metabolic syndrome and the pathogenetic mechanisms of metabolic syndrome were
      established. MATERIAL AND METHODS: There were 4 groups of pacients (110) with:
      metabolic syndrome, ischemic heart disease and hypertension, hypertention;
      control group. General clinical, instrumental, laboratory and statistical methods
      were used. RESULTS: The levels of immune factors - interleukin-6 in supernatants
      of mononuclear cells by 65%, sICAM-1 by 20% is elevated in patients with
      metabolic syndrome compared with the control group. The increasing of the content
      of saturated fatty acids by 9.4% and polyunsaturated fatty acid by 36.6% lead to
      fundamental breach of structural and functional properties of membranes. There is
      significant common carotid artery intima media thickness on average twice at the
      patients with metabolic syndrome and with ischemic heart disease and
      hypertension. CONCLUSIONS: The immunoinflammatory reactions were more revealed in
      the group of patients with metabolic syndrome than in other groups. The lipid
      state at patients with metabolic syndrome was changed more than in patients with
      hypertension or patients with ischemic heart disease and hypertension both.
      Moreover our data indicate the presence of structural changes in the vessel wall
      in patients with metabolic syndrome.

PMID- 28511166
TI  - Features of the immunohistochemical characteristics of primary tumors and
      recurrences of breast cancer after radical treatment.
AB  - INTRODUCTION: Appearance of Recurrence (RC) of breast cancer (BC) is associated
      with a high risk of distant metastases, needs re-treatment and indicates the
      tumor aggressiveness. It has been remained unclear the molecular characteristics
      both of the RC and primary tumors in patients with invasive forms of breast
      cancer after mastectomy by Madden. THE AIM: To explore the changing of the
      receptor status of the primary tumor and local RC in patients with breast cancer.
      MATERIALS AND METHODS: Immunohistochemical study were conducted on 262 patients
      with invasive breast cancer. Patients were divided into two groups: only local RC
      - 131 women and primary tumors of patients without local RC - also 131 persons.
      RESULTS: The difference of the receptor status of the tumors is presented. In the
      group of patients with recurrent "triplet negative" cancer and patients with
      positive reaction of epidermal growth factor (HER2neo) is more than 15.2%. In
      patients where RC (control group in the study) was not observed we have the mass
      greater proportion of tumors with positive hormone receptors in various
      combinations. CONCLUSIONS: Relapses are accompanied by lower levels of hormone
      receptors and increasing the frequency of "triplet negative" cancer as well as
      increasing of epidermal growth factor.

PMID- 28511165
TI  - Susceptibility of streptococcus pneumoniae to fluoroquinolones and macrolides in
      upper respiratory tract infections.
AB  - INTRODUCTION: Streptococcal species are known as the most common cause of
      bacterial upper respiratory tract infections (URTI). Once bacterial infection is
      diagnosed it demands empirical antibiotic prescription. On the other hand
      antimicrobial resistance is a global burden in today's medicine. For that reason,
      knowing of antimicrobial susceptibility patterns in population is an important
      background for successful treatment of bacterial caused URTI. The aim of this
      study was to analyze S. pneumoniae resistance and susceptibility patterns to
      fluoroquinolones and macrolides in URTI. MATERIALS AND METHODS: The results of
      microbiological examination of 2,055 pharyngeal swabs taken from patients with
      bacterial caused tonsillitis, pharyngitis and laryngitis were analyzed.
      Antimicrobial susceptibility testing for levofloxacin, ofloxacin, gatifloxacin,
      erythromycin, clarithromycin, azithromycin was performed with the disk-diffusion
      method. RESULTS: The incidence of S. pneumoniae in the etiological structure of
      bacterial caused URTI was increasing from 22.47% of cases in 2011 to 36.48% in
      2015. The susceptibility of this microorganism to ofloxacin, gatifloxacin and
      levofloxacin decreased from 96.25%, 100% and 95.00% in 2011 to 44.22%, 65.99% and
      62.59% in 2015 respectively. The susceptibility of S. pneumoniae to erythromycin,
      azithromycin and clarithromycin also decreased from 30.00%, 63.75% and 41.25% in
      2011 to 6.80%, 26.53%, 27.21 in 2015. CONCLUSIONS: Among investigated antibiotics
      levofloxacin can be recommended for empiric therapy of URTI because of high
      pneumococci susceptibility to this drug.

PMID- 28511167
TI  - Gut microbiota changes as a risk factor for obesity.
AB  - INTRODUCTION: The number of obese people in recent decades is increasing
      significantly. Among the many aspects of obesity in the last decade, the role and
      importance of changes in the gut microbiota (GM) attracts special attention. The
      aim of the review was to analyze the results of studies, focused on the role of
      gut microbiota in the obesity development. MATERIALS AND METHODS: Screening was
      conducted on 33 researches, which examined the role of the gut microbiota balance
      in the development of obesity. Among them, 13 studies were selected for more
      detailed analysis. RESULTS: Obesity revealed typical changes in GM: an increase
      in the number of microbes of the genus Firmicutes and a decrease in the number of
      microbes of the genus Bacteroeidetes, which is particularly vividly demonstrated
      by studies of rodents. In obese mice, the microfamilies of the genus Firmicutes
      account for 80% of all GM (in control animals 60%), and the number of
      microorganisms of the genus Bacteroeidetes decreases by half (from 40 to 20%),
      compared to mice with normal weight. CONCLUSION: Despite the complexity of the
      question of the relationship between GM and obesity, the totality of the data
      received, especially the results of experimental studies, affirm the thesis that
      changes in GM may contribute to the development of obesity.

PMID- 28511169
TI  - Efficiency comparison of tofacitinib and budesonid in treatment of nonspecific
      ulcerative colitis.
AB  - INTRODUCTION: A constant interest to explore NUC is caused by the global trend
      showing a rise in colitis mobidity rate. According to a series of epidemiological
      studies, the highest incidence of NUC occurs in young age groups, which leads to
      significant loss of working capacity and high level of incapacitation. One of the
      leading roles in the pathogenesis of this disease is reportedly played by
      immunogenetic theory. To date, the main practical technique of NUC diagnostics is
      colonoscopy. To assess the activity level, the Mayo score is used most
      frequently. The aim of NUC treatment is to achieve and maintain remission as well
      as improve the patients' life quality. One of the main achievements of
      contemporary gastroenterology is practical introduction of such high-performance
      preparations as mononuclear antibodies to TNF- alpha. AIM: To compare the impact
      of tofacitinib and budesonid on the mucous membrane of NUC patients. MATERIAL AND
      METHODS: Over the past two years 498 colonoscopic surveys have been performed at
      the Therapeutics Department of Uzhhorod Central Rayon Hospital, of which 16
      patients have been chosen. Depending upon the treatment obtained, all the
      patients were divided into two groups: Group I - patients that were taking
      tofacitinib in constant doses of 10 mg/day; Group II - patients that were taking
      budesonid in doses of 9 mg/day. The Mayo score was used to assess the level of
      inflammation activity. RESULTS: By morbidity occurrence, proctosigmoiditis was
      diagnosticated in 5 (31.25%), sinistral colitis in 7 (43.75%), and total colitis
      in 4 (25.00%) patients. The values of the integrative Mayo index at the moment of
      primary examination were 8.89+/-1.17 and 8.29+/-1.11 in Groups I and II,
      correspondingly. The treatment with budesonid led to a 15.56% decline in
      inflammation activity, equaling to 7.00+/-1.15 points of the Mayo score. In
      response to the treatment with tofacitinib the value went down by 59.96%,
      equaling to 3.56+/-1.13 points of the Mayo score, which was reliably lower as
      compared with Group II ( r<0.05). CONCLUSIONS: The use of tofacitinib was
      observed to result in a reliably better curative effect as compared with
      budesonid, which fact was verified endoscopically.

PMID- 28511168
TI  - [The nonalcoholic steatohepatitis influence on the course and progression of
      ischemic heart disease].
AB  - INTRODUCTION: Nonalcoholic steatohepatitis (NASH) can be considered a risk factor
      of progression of diseases associated with atherosclerosis, especially ischemic
      heart disease (IHD) with a high probability of early myocardial infarction (MI).
      AIM: To study the peculiarities and nature of ischemic heart disease clinical
      picture in patients with concomitant NASH. MATERIALS AND METHODS: The study
      involved 58 patients with ischemic heart disease. The nature of ischemic heart
      disease according to outpatients was evaluated, an assessment of ECG,
      echocardioscopy changes and Holter-monitoring was performed. RESULTS: The
      ischemic heart disease and concomitant NASH was observed only in young and middle
      age patients, among whom 16 (61.5%) revealed the presence of visceral obesity
      type. The presence of this synthropy is accompanied by an aggressive course of
      coronary heart disease with early MI development. According to Seattle Angina
      Questionnaire scale is case of IHD with NASH combination more limitation of
      physical activity, less pleasure treatment, worse perception of the disease and a
      significant reduction in the life quality of patients were noted. The nature of
      myocardium bioelectric activity disorders did not differ in the comparison group
      and matched the angina functional class and myocardial infarction consequences.
      CONCLUSIONS: The presence of visceral obesity, NASH causes early and aggressive
      course of ischemic heart disease, which is accompanied by a high risk of MI and
      reduces the patients' quality of life.

PMID- 28511170
TI  - Mosaic Trisomy 9p in a Patient with Mild Dysmorphic Features and Normal
      Intelligence.
AB  - To the Editor: Partial and whole duplications of the short arm of chromosome 9
      have been commonly reported in the literature with characteristic phenotypic
      features and intellectual disabilities. The clinical features of 9p duplications
      are broad and can include growth retardation, developmental delay, intellectual
      disability, microbrachycephaly, deep set eyes, hypertelorism, downslanting
      palpebral fissures, prominent nasal root, bulbous nasal tip, low-set ears, short
      fingers and toes with hypoplastic nails, and delayed bone age (Bonaglia et al.,
      2002; Zou et al., 2009; Guilherme et al., 2014).

PMID- 28511171
TI  - Clinical Outcome of Patients with Raised Intraepithelial Lymphocytes with Normal
      Villous Architecture on Duodenal Biopsy.
AB  - INTRODUCTION: The finding of a raised intraepithelial lymphocytes (IELs) count
      with normal villous architecture is of sufficient clinical importance to be
      reported in routine duodenal biopsies. AIM: To study the clinical and demographic
      data of patients with isolated increased IELs on duodenal biopsy. METHODS: A
      single-tertiary-centre retrospective study was carried out with a review of
      medical records of patients with increased IELs. Patients from 2012 to 2014, >18
      years with at least one biopsy from the second part of the duodenum with
      increased IELs; defined as >25 IELs/100 enterocytes, with preserved villous
      architecture were identified from our histopathology database with exclusion of
      patients with coeliac disease (CD).Clinical and demographic data were recorded
      following a chart review. CD was diagnosed by the attending physician based on
      the Physician Global Assessment. Data was compared between groups using a Student
      t test and ORs were calculated as appropriate. Statistical significance was set a
      priori at p < 0.05. RESULTS: Over 24 months, 6,244 patients were found to have
      duodenal biopsies and 114 (1.8%) had isolated increased IELs. Of the patients
      with increased IELs, the mean age was 50 years and 34 (30%) were male. Follow-up
      was available in 75 (65%) of these and CD was subsequently diagnosed in 32% (n =
      24). CD was associated with the female gender (22 out of 24 vs. 39 out of 51, OR
      7.5, older age 55 vs. 41 years, p < 0.04), and higher IEL count with an IEL of
      >40 in 11 out of 24 (46%) with CD vs. 12 out of 51 (24%) without CD, p = 0.0006.
      CONCLUSION: It is a non-specific but important finding, as it can have clinical
      implications.

PMID- 28511173
TI  - Is Occupational Complexity Associated with Cognitive Performance or Decline?
      Results from the Australian Longitudinal Study of Ageing.
AB  - BACKGROUND: Long-term protective associations proposed between previous complex
      occupational tasks and cognitive functioning in later life point to work roles
      contributing to cognitive reserve. OBJECTIVE: To examine occupational complexity
      involving data, people, and things in relation to the level of, and rate of
      change in, cognitive functioning. METHODS: Participants were 1,290 members of the
      Australian Longitudinal Study of Ageing and initially aged 65-102 years (mean =
      79). Information about main lifetime occupation was collected retrospectively.
      Cognition was assessed 4 times over a 13-year interval. RESULTS: In multilevel
      models adjusted for demographics, medical conditions, and depressive symptoms,
      higher complexity involving data was associated with faster speed (beta = 0.73, p
      < 0.001), better memory (beta = 0.32, p < 0.05), and mental status (beta = 0.40,
      p < 0.001) at baseline. These associations remained statistically reliable after
      adjusting for complexity with people and things, sedentary and heavy physical
      work, retirement age, and leisure activity. Complexity with things was associated
      with slower speed (beta = -0.50, p < 0.001) and poorer mental status (beta = 
      0.26, p < 0.01) and was not explained by other variables. There were no
      associations of occupational complexity with rates of cognitive decline over
      time. CONCLUSION: Older individuals retired from occupations characterized by
      higher complexity with data maintain their cognitive advantage over those with
      lower complexity into older adulthood, although without additional moderation of
      this advantage in terms of less postretirement cognitive decline. Complexity of
      work with things confers a negative relation to cognition whilst also not
      affecting postretirement cognitive change. Although the relative contributions of
      occupation or other early life influences for cognition remain to be established,
      it nevertheless may be beneficial to promote workplace design strategies and
      interventions that incorporate complex activities, particularly tasks involving
      data.

PMID- 28511172
TI  - Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal
      Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and
      Everolimus.
AB  - BACKGROUND: This analysis compared efficacy, renal function, and histology in
      kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus
      (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a
      randomized trial in kidney transplant recipients who received a single 3 mg/kg
      dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r
      ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or
      BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo
      donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on
      protocol biopsies at 12 months, and the incidence of acute rejection, estimated
      glomerular filtration rate (eGFR) and proteinuria at 36 months. RESULTS: At 12
      months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in
      subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular
      atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At
      36 months, there were no differences in the incidence of treatment failure (19.0
      vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8
      vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 +/- 1.05 vs.
      0.62 +/- 0.75 vs. 0.71 +/- 1.24). eGFR was lower in the BAS/EVR compared to that
      in the BAS/MPS group (53.4 +/- 20.9 vs. 50.8 +/- 19.5 vs. 60.7 +/- 21.2
      mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 +/- 23
      vs. 47.5 +/- 22.6 vs. 53.6 +/- 27.8 mL/min/1.73 m2, p = 0.207). CONCLUSION: In
      this cohort, the use of EVR and reduced TAC concentrations were associated with
      comparable efficacy, renal function, and histological parameters compared to the
      standard-of-care immunosuppressive regimen.

PMID- 28511174
TI  - Noninvasive Prenatal Detection of Trisomy 21 by Targeted Semiconductor
      Sequencing: A Technical Feasibility Study.
AB  - OBJECTIVE: To develop an alternate noninvasive prenatal testing method for the
      assessment of trisomy 21 (T21) using a targeted semiconductor sequencing
      approach. METHODS: A customized AmpliSeq panel was designed with 1,067 primer
      pairs targeting specific regions on chromosomes 21, 18, 13, and others. A total
      of 235 samples, including 30 affected with T21, were sequenced with an Ion
      Torrent Proton sequencer, and a method was developed for assessing the
      probability of fetal aneuploidy via derivation of a risk score. RESULTS:
      Application of the derived risk score yields a bimodal distribution, with the
      affected samples clustering near 1.0 and the unaffected near 0. For a risk score
      cutoff of 0.345, above which all would be considered at "high risk," all 30 T21
      positive pregnancies were correctly predicted to be affected, and 199 of the 205
      non-T21 samples were correctly predicted. The average hands-on time spent on
      library preparation and sequencing was 19 h in total, and the average number of
      reads of sequence obtained was 3.75 million per sample. CONCLUSION: With the
      described targeted sequencing approach on the semiconductor platform using a
      custom-designed library and a probabilistic statistical approach, we have
      demonstrated the feasibility of an alternate method of assessment for fetal T21.

PMID- 28511175
TI  - Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle
      Aspiration Needle: First Experience.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is a well-established first-line invasive modality for mediastinal
      lymph node staging in lung cancer patients and in the diagnostic workup of
      patients with mediastinal adenopathy. With the current 21- and 22-gauge (G) EBUS
      TBNA needles, the procedure can be limited by the degree of flexibility in the
      needle and the size of the lumen in tissue acquisition. OBJECTIVE: We report our
      initial experience with a first-generation flexible 19-G EBUS-TBNA (Flex 19G;
      Olympus Respiratory America, Redmond, WA, USA) needle with regards to efficacy
      and safety. METHODS: The Flex 19G EBUS-TBNA needle was used in 47 selected
      patients with enlarged hilar and/or mediastinal lymphadenopathy at 3 centers. The
      standard Olympus EBUS scope with a 2.2-mm working channel was used in all cases.
      RESULTS: The diagnostic yield of the Flex 19G needle according to clinical
      cytopathology reports was 89% (42/47). The diagnosis and their respective
      diagnostic yield with the Flex 19G EBUS-TBNA needle were malignancy 24/27 (89%),
      sarcoidosis 13/14 (93%), and reactive lymph node hyperplasia 5/6 (83%). The mean
      short axis of the sampled lymph nodes was 19 +/- 9 mm. No complications occurred
      except for 1 instance of moderate bleeding, which did not require intervention
      beyond suctioning and subsequently resolved. All 13 patients diagnosed with
      adenocarcinoma by the 19-G needle had sufficient tissue for genetic testing.
      CONCLUSION: EBUS-TBNA using the first-generation Flex 19G needle is feasible and
      safe with promising diagnostic yield while providing a greater degree of flexion
      with the Olympus EBUS scope. Additional clinical evaluations are warranted.

PMID- 28511176
TI  - Aging and the Inevitable Limit to Human Life Span.
AB  - There is a long-lasting debate about a natural limit to human life span, and it
      has been argued that the maximum reported age at death, which has not increased
      for ca 25 years, fluctuates around 115 years, even if some persons live beyond
      this age. We argue that the close connection of species-specific longevity with
      life history strategies explains why human life span is limited and cannot reach
      the considerably longer life spans of several other species.

PMID- 28511177
TI  - Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family
      with a New Recessive Mutation (S553L) Compared to a Family with a Dominant
      Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter.
AB  - BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited
      disorder manifested by hyperkalemia and hypertension. The following four
      causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3
      genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly
      dominant. A few cases with autosomal recessive disease were described. The
      mechanism of these 2 modes of inheritance is not clear. In the recessive form,
      the phenotype of heterozygotes is not well described. METHODS: Clinical and
      genetic investigation of members of 2 families was performed, one with recessive
      FHHt, and the other, an expansion of a family with Q309R KLHL3 dominant mutation,
      previously reported by us. Urinary exosomal sodium chloride cotransporter (NCC)
      was measured. RESULTS: A family with recessive FHHt caused by a new KLHL3
      mutation, S553L, is described. This consanguineous Jewish family of Yemenite
      extraction, included 2 homozygous and 7 heterozygous affected subjects. Increased
      urinary NCC was found in the affected members of the family with dominant Q309R
      KLHL3 mutation. In the recessive S553L family, homozygotes appeared to have
      increased urinary NCC abundance. Surprisingly, heterozygotes seemed to have also
      increased urinary NCC, though at an apparently lower degree. This was not
      accompanied by a clinical phenotype. CONCLUSIONS: A new recessive mutation in
      KLHL3 (S553L) was identified in FHHt. Increased urinary NCC was found in affected
      members (heterozygous) with dominant KLHL3 Q309R, and in affected members
      (homozygous) of the recessive form. Unexpectedly, in the recessive disease,
      heterozygotes seemed to have increased urinary NCC as well, apparently not
      sufficient quantitatively to produce a clinical phenotype.

PMID- 28511178
TI  - Descriptions of Apoplexy by Joseph Frank in the Beginning of the Nineteenth
      Century in Vilnius.
AB  - In the beginning of the 19th century, apoplexy was understood to be a disease of
      the cerebral blood vessels, manifesting with a sudden weakening or extinction of
      sensation and the patient's inability to move. In this study, we examined the
      situation of neurology in the beginning of the 19th century in Vilnius through
      the perspective of a nervous system disease - apoplexy. Case reports and
      descriptions of apoplexy in the textbook and memoirs by Joseph Frank (1771-1842),
      descriptions of patients with apoplexy from the proceedings of Vilnius University
      Clinic were analysed. It was identified that the main cause of apoplexy was not
      an imbalance of the four humours but the pathology of cerebral blood vessels.
      However, following ancient tradition, the principles of recreation and moderation
      were thought to be important for the prevention of apoplexy, and bloodletting and
      diet were believed to be essential for the treatment.

PMID- 28511179
TI  - Vascular Access in the Elderly: Does One Size Fit All?

PMID- 28511180
TI  - Response Predictors of S-1, Cisplatin, and Docetaxel Combination Chemotherapy for
      Metastatic Gastric Cancer: Microarray Analysis of Whole Human Genes.
AB  - OBJECTIVES: The aim of this study was to identify biomarkers for predicting the
      efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric
      cancer using microarrays of biopsy specimens before chemotherapy. METHODS:
      Nineteen samples were taken from 19 patients with unresectable metastatic gastric
      cancer who received DCS as a first-line therapy. Laser capture microdissection
      was performed, and total cellular RNA was extracted from each microdissected
      sample. Whole-gene expression was analyzed by microarray, and the difference in
      mRNA expression observed with the microarrays was confirmed by quantitative real
      time PCR. Immunohistochemical staining was performed using clinical tissue
      sections obtained by endoscopic biopsy. RESULTS: Eleven patients were identified
      as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine
      genes showed significant differences in relative expression ratios between tumor
      and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for
      distinguishing gene expression between 11 early responders and 8 nonresponders.
      Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and
      ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for
      validation were well correlated with those 4 genes in microarrays. CONCLUSION:
      The genes identified may serve as efficient biomarkers for personalized cancer
      targeted therapy.

PMID- 28511181
TI  - 1-CMDb: A Curated Database of Genomic Variations of the One-Carbon Metabolism
      Pathway.
AB  - BACKGROUND: The one-carbon metabolism pathway is vital in maintaining tissue
      homeostasis by driving the critical reactions of folate and methionine cycles. A
      myriad of genetic and epigenetic events mark the rate of reactions in a tissue
      specific manner. Integration of these to predict and provide personalized health
      management requires robust computational tools that can process multiomics data.
      The DNA sequences that may determine the chain of biological events and the
      endpoint reactions within one-carbon metabolism genes remain to be
      comprehensively recorded. Hence, we designed the one-carbon metabolism database
      (1-CMDb) as a platform to interrogate its association with a host of human
      disorders. METHODS: DNA sequence and network information of a total of 48 genes
      were extracted from a literature survey and KEGG pathway that are involved in the
      one-carbon folate-mediated pathway. The information generated, collected, and
      compiled for all these genes from the UCSC genome browser included the single
      nucleotide polymorphisms (SNPs), CpGs, copy number variations (CNVs), and miRNAs,
      and a comprehensive database was created. Furthermore, a significant correlation
      analysis was performed for SNPs in the pathway genes. RESULTS: Detailed data of
      SNPs, CNVs, CpG islands, and miRNAs for 48 folate pathway genes were compiled.
      The SNPs in CNVs (9670), CpGs (984), and miRNAs (14) were also compiled for all
      pathway genes. The SIFT score, the prediction and PolyPhen score, as well as the
      prediction for each of the SNPs were tabulated and represented for folate pathway
      genes. Also included in the database for folate pathway genes were the links to
      124 various phenotypes and disease associations as reported in the literature and
      from publicly available information. CONCLUSION: A comprehensive database was
      generated consisting of genomic elements within and among SNPs, CNVs, CpGs, and
      miRNAs of one-carbon metabolism pathways to facilitate (a) single source of
      information and (b) integration into large-genome scale network analysis to be
      developed in the future by the scientific community. The database can be accessed
      at http://slsdb.manipal.edu/ocm/.

PMID- 28511182
TI  - Cannabis Use among People Entering Drug Treatment in Europe: A Growing
      Phenomenon?
AB  - This paper explores European and national trends in specialised drug treatment
      entry for cannabis-related problems. The analysis is based on data for the years
      2003-2014 from 22 European countries. Between 2003 and 2014, the overall number
      and proportion of primary cannabis-related first-time entrants increased
      significantly. A joinpoint regression analysis indicates that the overall
      increase of cannabis treatment entries is continuous, although country-related
      differences are observed. Possible explanations for the increase and different
      time trends are discussed including an increase in cannabis prevalence and
      cannabis-related problems, changes in risk perception, increases in cannabis
      potency, changes in referral practices and increased availability and
      accessibility of treatment services.

PMID- 28511184
TI  - Are We Overlooking Stroke Chameleons? A Retrospective Study on the Delayed
      Recognition of Stroke Patients.
AB  - BACKGROUND AND PURPOSE: New effective recanalization therapies are currently
      available for acute ischemic stroke; yet a vast majority of stroke patients are
      left untreated. The lack of early recognition may be because often times, stroke
      patients present with atypical manifestations that resemble other conditions
      (which are referred to as "stroke chameleons"). We set to study the proportion of
      patients with delayed stroke recognition in a single center. METHODS: We
      performed a retrospective analysis of a prospectively collected data over a 9
      year period. All adult patients discharged with the diagnosis of ischemic stroke
      or transient ischemic attack (TIA) were identified and traced for their diagnosis
      on admission. Those cases with a diagnosis other than ischemic stroke or TIA on
      admission were identified as possible stroke chameleons and categorized into
      different groups according to the occurrence of neurological or non-neurological
      manifestations at presentation. RESULTS: Of 2,303 cases with discharge diagnosis
      of ischemic stroke or TIA, 919 (39.9%) were found to be possible stroke
      chameleons. More than half of these patients (58.4%) presented with neurological
      manifestations including disorders of the somatic sensation (33%), alteration of
      consciousness (30%), and disorders of speech/language (11%). The remaining
      possible stroke chameleons had manifestations pertaining to other organ systems
      such as cardiopulmonary, gastrointestinal, systemic infection, trauma, and
      thromboembolic events elsewhere. CONCLUSIONS: In our cohort, a surprisingly large
      percentage of possible stroke chameleons was observed. It is important to confirm
      our findings, study the impact on clinical outcome, and develop strategies for
      early stroke patient recognition.

PMID- 28511185
TI  - Evaluation of Total, Active, and Specific Myeloperoxidase Levels in Women with
      and without Endometriosis.
AB  - Myeloperoxidase (MPO) is a proinflammatory enzyme and a marker for neutrophil
      activation and oxidative stress. Since oxidative stress and inflammation are
      linked to the pathogenesis of endometriosis, we hypothesized that the total,
      active, and specific (active/total) MPO levels were significantly different in
      plasma of women with and without endometriosis. Samples were selected from our
      biobank from women with endometriosis (n = 212) and controls without
      endometriosis (n = 121) across the menstrual cycle. Total MPO plasma levels were
      measured by immunoassay and MPO activity by enzymatic assay. Total and active MPO
      levels did not differ significantly among endometriosis cases and controls,
      whereas the specific MPO activity was significantly lower in women with
      endometriosis than that in controls (p = 0.0159). After the subdivision of
      control patients into women with a normal pelvis and women with other benign
      gynecological disorders, a significant difference was observed only between women
      with endometriosis and women with other benign gynecological disorders (p =
      0.0266). In conclusion, systemic MPO levels may not be suited as a single
      biomarker for endometriosis. Our data support the involvement of MPO in other
      gynecological disorders but do not provide any evidence for an association with
      endometriosis.

PMID- 28511186
TI  - Search for Internal Cancers in Mice Tattooed with Inks of High Contents of
      Potential Carcinogens: A One-Year Autopsy Study of Red and Black Tattoo Inks
      Banned in the Market.
AB  - BACKGROUND AND OBJECTIVE: Tattoo ink stock products often contain potential
      carcinogens, which on large-scale population exposure may be clinically relevant.
      The aim of this autopsy study in mice was to screen major organs for clinical and
      subclinical cancers. METHODS: Mice were tattooed on their backs. In total, 48
      mice were included and divided into 4 groups; 11 mice tattooed black, 10 tattooed
      red, and 5 mice serving as untreated controls. A group of 22 mice with black
      tattoos and exposed to ultraviolet radiation (UVR) were also studied. The black
      and red inks were both stock products banned on the Danish market due to the
      measured contents of potential carcinogens; benzo(a)pyrene and 2-anisidine,
      respectively. The mice were housed for 1 year after tattooing, and autopsy study
      on internal organs was performed. Tissue samples were systematically taken from
      major organs for screening of subclinical changes, not detected by visual
      examination. Any observed deviation from normal structure was subject to biopsy
      and light microscopy. RESULTS: All mice survived the 1-year observation period.
      Autopsy revealed no macroscopic signs of cancer. Microscopic search of internal
      organs showed no subclinical or clinical cancer. CONCLUSION: Despite extensive
      tattoos with 2 banned inks, the long-term observation in mice showed no internal
      cancers nor was the combination of carcinogen and UVR associated with cancer.
      Lack of observed malignancy might be explained by the fact that tattooing is only
      a single dose exposure. Registered data on carcinogens relies on repeated or
      chronic exposures. The study does not support the hypothesis that tattooing
      causes cancer.

PMID- 28511188
TI  - Calprotectin in Daily Practice: Where Do We Stand in 2017?
AB  - BACKGROUND: To make a distinction between organic and functional disease is
      essential for gastroenterologists in their daily practice, but it may be
      challenging, given the variety and aspecificity of gastrointestinal symptoms
      among the general population. The clinician aim is to avoid diagnostic delay and
      to restrict unnecessary invasive and expensive exams. SUMMARY: Faecal markers, in
      particular faecal calprotectin (FC), have given proof of being reliable markers
      of intestinal inflammation with good clinical sensitivity. Calprotectin is useful
      in the differential diagnosis between inflammatory bowel disease and irritable
      bowel syndrome, as well as in the follow-up of inflammatory bowel disease
      patients and in predicting treatment response, with an excellent correlation with
      endoscopic activity. Its role in collagenous colitis and infectious colitis is
      less clear and still under investigation. Key Message: Despite the growing
      evidence supporting its use, many clinicians are uncomfortable in dosing FC, due
      to its low specificity and the variability of cut-off values. Indeed there are no
      clear guidelines about how to manage patients with intermediate levels of FC. The
      aim of this article is to review recent literature on calprotectin and its use.
      The strong points and the limits of FC measurement will be analysed, and a
      practical approach in the daily clinical routine will be proposed.

PMID- 28511187
TI  - The Differential Effects of Erythropoietin Exposure to Oxidative Stress on
      Microglia and Astrocytes in vitro.
AB  - The neonatal brain is especially susceptible to oxidative stress owing to its
      reduced antioxidant capacity. Following hypoxic-ischemic (HI) injury, for
      example, there is a prolonged elevation in levels of hydrogen peroxide (H2O2) in
      the immature brain compared to the adult brain, resulting in lasting injury that
      can lead to life-long disability or morbidity. Erythropoietin (Epo) is one of few
      multifaceted treatment options that have been promising enough to trial in the
      clinic for both term and preterm brain injury. Despite this, there is a lack of
      clear understanding of how Epo modulates glial cell activity following oxidative
      injury, specifically, whether it affects microglia (Mg) and astrocytes (Ast)
      differently. Using an in vitro approach using primary murine Mg and Ast subjected
      to H2O2 injury, we studied the oxidative and inflammatory responses of Mg and Ast
      to recombinant murine (rm)Epo treatment. We found that Epo protects Ast from H2O2
      injury (p < 0.05) and increases secreted nitric oxide levels in these cells (p <
      0.05) while suppressing intracellular reactive oxygen species (p < 0.05) and
      superoxide ion (p < 0.05) levels only in Mg. Using a multiplex analysis, we noted
      that although H2O2 induced the levels of several chemokines, rmEpo did not have
      any significant specific effects on their levels, either with or without the
      presence of conditioned medium from injured neurons (NCM). Ultimately, it appears
      that rmEpo has pleiotropic effects based on the cell type; it has a protective
      effect on Ast but an antioxidative effect only on Mg without any significant
      modulation of chemokine and cytokine levels in either cell type. These findings
      highlight the importance of considering all cell types when assessing the
      benefits and pitfalls of Epo use.

PMID- 28511189
TI  - The Role of Audiometry prior to High-Dose Cisplatin in Patients with Head and
      Neck Cancer.
AB  - OBJECTIVES: To analyze the role of audiometry in considering change to a less
      ototoxic treatment in head and neck cancer (HNC) patients. METHODS: Consecutive
      patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and
      February 2015 were enrolled. Audiometry was performed at baseline and before
      cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was
      considered with audiometric decreases >25 dB. RESULTS: A total of 103 patients
      were included; the median age of the patients was 59 years (range 18-75).
      Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty
      two participants (41%) did not commence high-dose cisplatin because of baseline
      audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40
      (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss
      between initial and final audiometries showed a hearing loss at 4 and 8 kHz in
      both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a
      lower dose of cisplatin. The outcome was not significantly altered when cisplatin
      was replaced with carboplatin or cetuximab. CONCLUSIONS: Audiometric alterations
      are common in HNC with high-dose cisplatin, and switching to a less ototoxic
      regimen does not adversely affect outcome. Audiometric examination could help to
      prevent hearing loss in this population.

PMID- 28511190
TI  - Psychotherapy Technique Related to Changes in Anxiety Symptoms With a
      Transdiagnostic Sample.
AB  - The current study examined how techniques in a psychodynamic model of therapy
      (Blagys and Hilsenroth, Clin Psychol Sci Pract. 7, 167-188, 2000) were related to
      changes in anxiety symptoms across early treatment process among a
      transdiagnostic sample of patients with primary anxiety disorder, subclinical
      anxiety disorder, and no anxiety disorder. Secondary analyses examined the use of
      specific psychodynamic techniques in relation to symptom change. Results revealed
      that therapists' use of psychodynamic-interpersonal (PI) techniques were
      significantly and directly related to changes in anxiety symptoms, in line with
      previous findings (Pitman, Slavin-Mulford, and Hilsenroth, J Nerv Ment Dis. 202,
      391-396, 2014). In addition, patients with co-occurring axis I and II disorders
      demonstrated positive changes in anxiety symptoms regardless of level of PI
      technique used, whereas patients without co-occurring disorders experienced
      greater improvement with more PI. Implications for transdiagnostic treatment
      protocols for anxiety, notably Leichsenring and Salzer's (Psychotherapy 51, 224,
      2104) Unified Psychodynamic Protocol for Anxiety Disorders, are discussed in
      relation to the current findings.

PMID- 28511191
TI  - Death by Suicide Within 1 Week of Hospital Discharge: A Retrospective Study of
      Root Cause Analysis Reports.
AB  - There is a high risk for death by suicide after discharge from an inpatient
      mental health unit. To better understand system and organizational factors
      associated with postdischarge suicide, we reviewed root cause analysis reports of
      suicide within 7 days of discharge from across all Veterans Health Administration
      inpatient mental health units between 2002 and 2015. There were 141 reports of
      suicide within 7 days of discharge, and a large proportion (43.3%, n = 61)
      followed an unplanned discharge. Root causes fell into three major themes
      including challenges for clinicians and patients after the established process of
      care, awareness and communication of suicide risk, and flaws in the established
      process of care. Flaws in the design and execution of processes of care as well
      as deficits in communication may contribute to postdischarge suicide. Inpatient
      teams should be aware of the potentially heightened risk for suicide among
      patients with unplanned discharges.

PMID- 28511192
TI  - Individual Variation in Hunger, Energy Intake, and Ghrelin Responses to Acute
      Exercise.
AB  - PURPOSE: This study aimed to characterize the immediate and extended effect of
      acute exercise on hunger, energy intake, and circulating acylated ghrelin
      concentrations using a large data set of homogenous experimental trials and to
      describe the variation in responses between individuals. METHODS: Data from 17 of
      our group's experimental crossover trials were aggregated yielding a total sample
      of 192 young, healthy males. In these studies, single bouts of moderate to high
      intensity aerobic exercise (69% +/- 5% VO2 peak; mean +/- SD) were completed with
      detailed participant assessments occurring during and for several hours
      postexercise. Mean hunger ratings were determined during (n = 178) and after (n =
      118) exercise from visual analog scales completed at 30-min intervals, whereas ad
      libitum energy intake was measured within the first hour after exercise (n = 60)
      and at multiple meals (n = 128) during the remainder of trials. Venous
      concentrations of acylated ghrelin were determined at strategic time points
      during (n = 118) and after (n = 89) exercise. RESULTS: At group level, exercise
      transiently suppressed hunger (P < 0.010, Cohen's d = 0.77) but did not affect
      energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001,
      Cohen's d = 0.10) and remained significantly lower than control (no exercise)
      afterward (P < 0.024, Cohen's d = 0.61). Between participants, there were notable
      differences in responses; however, a large proportion of this spread lay within
      the boundaries of normal variation associated with biological and technical
      assessment error. CONCLUSION: In young men, acute exercise suppresses hunger and
      circulating acylated ghrelin concentrations with notable diversity between
      individuals. Care must be taken to distinguish true interindividual variation
      from random differences within normal limits.

PMID- 28511193
TI  - A Validation Study of the Fitbit One in Daily Life Using Different Time
      Intervals.
AB  - PURPOSE: Accelerometer-based wearables can provide the user with real-time
      feedback through the device's interface and the mobile platforms. Few studies
      have focused on the minute-by-minute validity of wearables, which is essential
      for high-quality real-time feedback. This study aims to assess the validity of
      the Fitbit One compared with the ActiGraph GT3x + for assessing physical activity
      (i.e., steps, time spent in moderate, vigorous, and moderate-vigorous physical
      activity) in young adults using traditional time intervals (i.e., days) and
      smaller time intervals (i.e., minutes and hours). METHODS: Healthy young adults
      (N = 34) wore the ActiGraph GT3x+ and a Fitbit One for 1 wk. Three aggregation
      levels were used: minute, hour, and day. Mixed models analyses, intraclass
      correlation coefficients, Bland-Altman analyses, and absolute error percentage
      for steps per day were conducted to analyze the validity for steps and minutes
      spent in moderate, vigorous, and moderate-vigorous physical activity. RESULTS: As
      compared with ActiGraph (mean = 9 steps per minute, 509 steps per hour and 7636
      steps per day), the Fitbit One systematically overestimated physical activity for
      all aggregation levels: on average 0.82 steps per minute, 45 steps per hour, and
      677 steps per day. Strong and significant associations were found between
      ActiGraph and Fitbit results for steps taken (B = 0.72-0.89). Weaker but
      statistically significant associations were found for minutes spent in moderate,
      vigorous, and moderate-vigorous physical activity for all time intervals (B =
      0.39-0.57). CONCLUSIONS: Although the Fitbit One overestimates the step activity
      compared with the ActiGraph, it can be considered a valid device to assess step
      activity, including for real-time minute-by-minute self-monitoring. However,
      agreement and correlation between ActiGraph and Fitbit One regarding time spent
      in moderate, vigorous, and moderate-vigorous physical activity were lower.

PMID- 28511194
TI  - Brushing Your Way to Allergic Contact Dermatitis: Anethole Allergy.

PMID- 28511195
TI  - Safety Aspects of Postanesthesia Care Unit Discharge without Motor Function
      Assessment after Spinal Anesthesia: A Randomized, Multicenter, Semiblinded,
      Noninferiority, Controlled Trial.
AB  - BACKGROUND: Postanesthesia care unit (PACU) discharge without observation of
      lower limb motor function after spinal anesthesia has been suggested to
      significantly reduce PACU stay and enhance resource optimization and early
      rehabilitation but without enough data to allow clinical recommendations.
      METHODS: A multicenter, semiblinded, noninferiority randomized controlled trial
      of discharge from the PACU with or without assessment of lower limb motor
      function after elective total hip or knee arthroplasty under spinal anesthesia
      was undertaken. The primary outcome was frequency of a successful fast-track
      course (length of stay 4 days or less and no 30-day readmission). Noninferiority
      would be declared if the odds ratio (OR) for a successful fast-track course was
      no worse for those patients receiving no motor function assessment versus those
      patients receiving motor function assessment by OR = 0.68. RESULTS: A total of
      1,359 patients (98.8% follow-up) were available for analysis (93% American
      Society of Anesthesiologists class 1 to 2). The primary outcome occurred in 92.2%
      and 92.0%, corresponding to no motor function assessment being noninferior to
      motor function assessment with OR 0.97 (95% CI, 0.70 to 1.35). Adverse events in
      the ward during the first 24 h occurred in 5.8% versus 7.4% with or without motor
      function assessment, respectively (OR, 0.77; 95% CI, 0.5 to 1.19, P = 0.24).
      CONCLUSIONS: PACU discharge without assessment of lower limb motor function after
      spinal anesthesia for total hip or knee arthroplasty was noninferior to motor
      function assessment in achieving length of stay 4 days or less or 30-day
      readmissions. Because a nonsignificant tendency toward increased adverse events
      during the first 24 h in the ward was discovered, further safety data are needed
      in patients without assessment of lower limb motor function before PACU
      discharge.

PMID- 28511196
TI  - To Stop or Not, That Is the Question: Acute Pain Management for the Patient on
      Chronic Buprenorphine.

PMID- 28511197
TI  - Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs: Erratum.

PMID- 28511199
TI  - Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease Among Patients
      with Inflammatory Bowel Disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been increasingly
      identified in patients with inflammatory bowel disease (IBD). We aimed to
      determine risk factors of NAFLD in patients with IBD. METHODS: We examined 3
      groups of patients: IBD + NAFLD, IBD only, and NAFLD only. Data on demographics,
      body mass index, duration of IBD, type of medication use, laboratory data, and
      metabolic risk factors were collected. RESULTS: A total of 168 patients between
      the ages 19 and 82 were evaluated, 56 patients in each group. Patients with IBD +
      NAFLD were significantly older than IBD only patients 45.0 (+/-14.1) versus 35.0
      (+/-13), P = 0.007, and their mean body mass index was higher 30.4 (+/-10.2)
      versus 25.6 (+/-6.4); P = 0.002. IBD + NAFLD patients in comparison with IBD only
      patients had significantly longer duration of IBD (20 [+/-12.2] versus 10 [+/
      7.7], P = 0.004), had an increased risk of diabetes (16% versus 2%, P = 0.01),
      and obesity (40% versus 20%, P = 0.02). There were no differences in the mean age
      or the mean body mass index (32.6 versus 30.4, P = 0.07) between patients with
      IBD + NAFLD and NAFLD only. More patients were obese in the NAFLD only group
      compared with the IBD + NAFLD group (59% versus 40%, P = 0.03), had hypertension
      (55% versus 33%, P = 0.02), hyperlipidemia (53% versus 17.5%, P = 0.0001), and
      diabetes (40% versus 16%, P = 0.0001). CONCLUSIONS: IBD patients with NAFLD had
      longer disease duration of IBD and developed NAFLD with fewer metabolic risk
      factors than patients with NAFLD only. These findings suggest that there may be
      other factors that contribute to the development of NAFLD in the IBD population.

PMID- 28511200
TI  - Enteric Infection in Relapse of Inflammatory Bowel Disease: The Utility of Stool
      Microbial PCR Testing.
AB  - BACKGROUND: The similar presentations in relapse of inflammatory bowel disease
      (IBD) and enteric infection pose substantial barriers to diagnosis and treatment.
      The objective of this study was to investigate the incidence, etiology,
      predictors, and treatment of enteric infection in patients with IBD. METHODS: We
      reviewed the records of 214 patients with IBD who underwent 295 gastrointestinal
      pathogen panel and Clostridium difficile infection (CDI) polymerase chain
      reaction (PCR) stool tests during an exacerbation of symptoms. We collected
      baseline characteristics, PCR outcomes, and medication exposures. We tested for
      associations via the Chi-square test and the t-test. Logistic regression analysis
      was used to identify predictors of enteric infection. RESULTS: Of 295 PCR tests
      ordered during an exacerbation of symptoms, 38 (12.9%) were positive for CDI and
      41 (13.8%) were positive for 14 other pathogens, with E. coli species as the most
      common. A previous history of CDI or colonic involvement of IBD predicted CDI,
      whereas a previous colectomy predicted negative testing for CDI. The majority
      with CDI (24, 63.2%) received oral vancomycin and 15 (37.5%) with other enteric
      pathogens were treated for their infection. Patients with CDI had a longer median
      length of hospital stay (8.5 versus 4 days, P = 0.041). Patients who tested
      negative for enteric infections were more likely to have IBD medications added or
      up-titrated (P = 0.027). CONCLUSIONS: Enteric infection was detected in 79
      (26.8%) symptomatic patients with IBD , with CDI the most frequent followed by E.
      coli. Negative stool PCR testing was associated with changes in IBD management.
      Broad enteric PCR testing should be considered during relapse of IBD.

PMID- 28511198
TI  - Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with
      Inflammatory Bowel Disease: A Systematic Review and Practical Guide.
AB  - BACKGROUND: In asymptomatic patients with inflammatory bowel disease (IBD),
      "monitoring" involves repeated testing aimed at early recognition of disease
      exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin
      (FC) measurements to predict IBD relapses by a systematic literature review.
      METHODS: An electronic search was performed in Medline, Embase, and Cochrane from
      inception to April 2016. Inclusion criteria were prospective studies that
      followed patients with IBD in remission at baseline and had at least 2
      consecutive FC measurements with a test interval of 2 weeks to 6 months.
      Methodological assessment was based on the second Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS: A total of 1719
      articles were identified; 193 were retrieved for full text review. Six studies
      met eligibility for inclusion. The time interval between FC tests varied between
      1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements
      above the study's cutoff level had a 53% to 83% probability of developing disease
      relapse within the next 2 to 3 months. Patients with repeated normal FC values
      had a 67% to 94% probability to remain in remission in the next 2 to 3 months.
      The ideal FC cutoff for monitoring could not be identified because of the limited
      number studies meeting inclusion criteria and heterogeneity between selected
      studies. CONCLUSIONS: Two consecutively elevated FC values are highly associated
      with disease relapse, indicating a consideration to proactively optimize IBD
      therapy plans. More prospective data are necessary to assess whether FC
      monitoring improves health outcomes.

PMID- 28511201
TI  - ?

PMID- 28511202
TI  - [Protective Effects of Muller Glia Cells Towards Retinal Ganglion Cells].
AB  - INTRODUCTION: Muller glial cells carry out different tasks to warrant normal
      retinal functions. The aim of this study was to investigate if Muller cells also
      support retinal ganglion cells (RGC). MATERIALS AND METHODS: RGC were cultured
      for 24 hours in the presence or absence of Muller glial cells under normoxic (20%
      O2, 5% CO2) or hypoxic (0.2% O2, 5% CO2, 94.8% N2) culture conditions. The number
      of vital RGC and the length of the newly developed neurites were evaluated.
      RESULTS: Under normoxic conditions, RGC vitality was significantly higher (p <
      0.01) when cultured with Muller cells (62.85 +/- 2.06%) than without (47.29 +/-
      2.83%). Under hypoxia, RGC vitality was significantly higher (p < 0.01) in co
      cultures (41.07 +/- 2.28%) than in homotypic RGC cultures (28.49 +/- 2.16%). The
      maximum length of the newly developed neurites was found in the normoxic co
      culture (90.7 +/- 7.4 um), but showed only a minor difference (p = 0.04) when
      compared to the normoxic homotypic RGC culture. CONCLUSION: Muller glial cells
      support RGC under normoxic and hypoxic culture conditions. Length of newly
      developed neurites and number of surviving RGC are both parameters to evaluate
      cell vitality.

PMID- 28511204
TI  - [Current Immunization Status of Dusseldorf's Nursery School Children and Staff
      Members: A Cross-Sectional Study].
AB  - Background The local health authority (Gesundheitsamt) in Dusseldorf, Germany
      aimed to investigate the current immunization status of nursery school children
      and pedagogues in Dusseldorf, Germany. Furthermore, analysing the association
      between Dusseldorf's 5 social environment clusters and immunization status was of
      interest. Especially due to recent changes in the German Infection Protection Act
      closely monitoring adverse immunization trends becomes increasingly important.
      Methods Weighted cluster random sampling was used in order to draw a sample of 50
      nursery schools from the 5 social environment clusters. Questionnaires were sent
      to the nursery schools and data were subsequently analysed using descriptive
      statistics. Results The results indicate that 76.0% of the children were
      immunized in time against MMR, 68.2% against varicella and 75.4% against
      meningococcal serogroup C. Data indicated a higher number of immunized children
      among older age groups. 96.4% of staff members born after 1970 were not
      vaccinated against varicella, 17.9% were not immunized against MMR and 82.1% were
      not vaccinated against meningococcal serogroup C. Conclusion Immunization rates
      of children in nursery schools in Dusseldorf are far lower compared to local,
      federal and nationwide data of children's school entrance health examination.
      Especially in nursery schools that care for children younger than 12 months, herd
      immunity is crucial. Therefore, administering vaccines with a delay is considered
      to be precarious. Due to low response rates, inferential statistics could not be
      used and conclusions about the staff members' data are limited.

PMID- 28511203
TI  - [Intraindividual Keratoconus Progression].
AB  - Introduction Keratoconus is a typically bilateral, progressive-extending corneal
      disease. The aim of this work is to evaluate the intraindividual progression of
      keratoconus. Patients and Methods This single-center retrospective study of
      disease progression based on topographic data from non-operated keratoconus
      patients (n = 48) was examined over a period of two years. Seven topographical
      keratoconus indices derived from Scheimpflug tomography were used to compare both
      the initial findings, as well as the progression of the fellow eyes. Results The
      mean observation period was 3.3 +/- 0.9 years. The initial findings illustrated
      that a pair of eyes did not correlate with each other (p > 0.05). When comparing
      baseline and the progression of the individual indices, a negative correlation
      was found for all indices (p < 0.05). Progression and age did correlate for index
      smallest radius (Rmin, (R = 0.376, p = 0.008) and index of height decentration
      (IHD, R = 0.291, p = 0.045). Regarding the intraindividual progression, we found
      a weak correlation to the index of surface variance (ISV, R = - 0.399, p =
      0.005), index of vertical asymmetry (IVA, R = - 0.291, p = 0.045) and the
      keratoconus index (KI, R = 0.307, p = 0.038). Conclusions The intraindividual
      asymmetry, which is typical for keratoconus, could be verified. This study
      suggests that the progression of keratoconus in one eye is independent of the
      progression in the fellow eye. In this small group of patients, age relationship
      to keratoconus could not be demonstrated for all keratoconus indices.

PMID- 28511205
TI  - [Stability and Change of Medical Specialty of Residents over Four Years of
      Postgraduate Training in Germany].
AB  - Aim We analyzed medical residents' preferences in Germany with regard to the
      specialization fields after 4 years of postgraduate training and compared them to
      their preferences in the years before, e. g. at the end of undergraduate
      education in a gender comparative perspective, including the influence of
      parenthood. Methods The study is based on annual postal surveys of students of 7
      medical faculties in Germany from their last year of medical school ("Practical
      Year") until after 4 years of postgraduate training. The return rate at baseline
      was 48% and in the 4 surveys thereafter the rates were 85% and above. In all
      samples, about two-thirds of respondents were women, which corresponds to the
      actual gender distribution in under- and postgraduate training. Descriptive
      statistics and regression analyses were used. Results Compared to the end of
      undergraduate education, anaesthesiology and general practice were the
      disciplines which gained in attraction, whereas surgical disciplines lost
      significantly in their attraction. These developments were similar in both
      genders. Specialized internal medicine, paediatrics and gynaecology lost
      attraction among female physicians only. We found important correlations of
      disciplinary preferences with parenthood and with the preference for part-time
      work after graduation. Conclusion The data show that "feminization" is not the
      reason why both anaesthesiology and general practice gained in attraction, since
      this happened over the 4 years among both male and female physicians. The loss in
      attraction in all great clinical disciplines, especially in surgery, orthopaedics
      and urology, may lead to severe problems in supply of medical manpower in the
      hospital, especially when combined with preference for part-time work.

PMID- 28511207
TI  - ?

PMID- 28511208
TI  - ?

PMID- 28511206
TI  - ?
AB  - In the recent study by Verhoeven and Egger, 2015 and the recent letter to the
      editor by Boot et al. 2015 an emphasis is given to the best possible
      pharmacological treatment of 22q11-2 Deletion-Syndrome related psychoses. We
      would like to present the case of a 23-year old Cypriot patient with 22q11.2
      deletion syndrome who fulfilled criteria for treatment resistant schizophrenia
      (TRS). He was sequentially treated with aripiprazole, risperidone, olanzapine,
      haloperidol and a combination treatment with olanzapine and haloperidol.
      Clozapine was the only antipsychotic medication that has improved his condition.

PMID- 28511209
TI  - ?

PMID- 28511210
TI  - ?

PMID- 28511211
TI  - ?

PMID- 28511212
TI  - ?

PMID- 28511213
TI  - ?

PMID- 28511214
TI  - ?

PMID- 28511216
TI  - ?

PMID- 28511215
TI  - ?

PMID- 28511217
TI  - ?

PMID- 28511218
TI  - ?

PMID- 28511219
TI  - [Innovative Ultrasound: Contrast-Enhanced Ultrasound of the Kidneys].
AB  - Ultrasound examination of the kidneys with grey-scale imaging and colour Doppler
      ultrasound is the most common renal imaging modality. A few years ago, contrast
      enhanced ultrasound (CEUS) emerged as a non-invasive perfusion imaging modality
      to evaluate the renal vessels and microvascularisation. These contrast media
      contain intravenous microbubbles (sulfur hexafluoride), which have no deleterious
      effect on renal function. Being free of iodine, they also pose no risk for the
      thyroid gland. CEUS of the kidneys is mainly used for the evaluation of renal
      cysts and the analysis of renal lesions suspicious for malignancy. Also this
      method is used to visualise inflammation as well as renal perfusion after trauma
      or infarction.

PMID- 28511220
TI  - [Significance and Value of PSMA Ligands in Prostate Cancer].
AB  - In recent years, PSMA-targeting PET tracers such as 68Ga-PSMA-11 have shown
      promising results, thus contributing to a better management of prostate cancer
      patients. At the present time, 68Ga-PSMA-11 is most frequently used for
      diagnostic evaluation in the setting of biochemical recurrence of prostate
      cancer. In this context, the 68Ga-PSMA-11 PET/CT delivers superior detection
      rates compared to conventional imaging, especially for the detection of small,
      unsuspicious lesions or lesions in the presence of low PSA values. Furthermore,
      68Ga-PSMA PET imaging seems to be an encouraging alternative for the staging of
      high-risk patients, particularly in combination with multiparametric MRI. In
      addition to the increasing use of PSMA ligands in clinical diagnostics, some
      variants have also been successfully applied in therapy. Advanced metastasized
      prostate cancer patients showed a good response to PSMA radioligand therapy with
      tolerable side-effects after failure of guideline-compliant treatment.Due to
      recent developments, PSMA ligands will continue to play an important role in the
      management of prostate cancer patients and will be more widely used in the
      future.

PMID- 28511221
TI  - [PSMA-Radioguided Surgery for Salvage Lymphadenectomy in Recurrent Prostate
      Cancer].
AB  - Recently, the use of 111In-labeled PSMA-I&T-based radioguided surgery (111In-PSMA
      RGS) for salvage surgery using intraoperative ex-vivo gamma-probe measurements
      has been described by our group as a promising new and individual treatment
      concept in patients with localised recurrent prostate cancer (PC). 111In-PSMA-RGS
      allowed for the intraoperative identification of metastatic lesions with a
      sensitivity, specificity and accuracy of 92.3, 93.5 and 93.1%, respectively,
      compared to histopathology. 111In-PSMA-RGS was able to detect 5 additional lymph
      node metastases in 3 out of 31 patients compared to 68Ga-HBED-CC-PSMA PET. A PSA
      decline >50 and >90% was observed in 24/31 patients and 17/31 patients,
      respectively. In 19/31 patients even a complete biochemical response was
      observed. 10/31 patients received further PC-specific treatment after a median of
      125 days following 111In-PSMA-RGS. Surgery-related complications were observed in
      10 patients (Clavien-Dindo classification: grade 1 n=6, grade 3b n=4). 111In-PSMA
      RGS seems to be highly valuable for the intraoperative detection of small
      metastatic lesions in PC patients scheduled for salvage lymphadenectomy. It
      allows for an exact localisation and resection of metastatic tissue during 111In
      PSMA-RGS and thus is anticipated to have a beneficial influence on further
      disease progression. However, the identification of suitable patients on the
      basis of 68Ga-PSMA PET imaging and clinical parameters is critical to obtain
      satisfactory results.

PMID- 28511223
TI  - ?

PMID- 28511222
TI  - Cellular Angiofibroma of the Spermatic Cord.
AB  - Cellular angiofibromas are rare, slow-growing mesenchymal tumours, most often
      localised in the vulva and perineum of women. We present a case of a 60-year-old
      male with a 7-cm large cellular angiofibroma in the inguinal canal extending
      toward the testis, detected after inguinal herniorraphy. Inguinal orchiectomy was
      performed and the pathology report revealed a cellular angiofibroma containing a
      lot of mast cells in the stroma, which was collagenised with spindle-shaped cells
      and characterised by hyalinised vascular structures. The localisation and nature
      of this type of mass makes initial diagnosis difficult. Differential diagnosis is
      important to rule out histologically malignant aggressive angiomyxomas and other
      solitary fibrous tumours. As local recurrence may occur after resection, long
      term follow-up is necessary.

PMID- 28511224
TI  - ?

PMID- 28511225
TI  - Comment on The 100 Most-Cited Articles Focused on Ultrasound Imaging: A
      Bibliometric Analysis.

PMID- 28511226
TI  - Contrast-Enhanced Ultrasound in the Follow-Up of Endoleaks after Endovascular
      Aortic Repair (EVAR).
AB  - Endovascular aortic repair (EVAR) has become established in the treatment of
      abdominal aortic aneurysms and shows potential benefits such as a low
      perioperative morbidity and a short hospitalization duration. The follow-up after
      EVAR primarily consists of lifelong postinterventional imaging of the aneurysm
      size in order to detect complications such as endoleaks or stent dislocation.
      Computed tomography angiography, an imaging modality that uses ionizing radiation
      and that relies on a contrast medium which is dependent on thyroid and renal
      function, is widely used for follow-up. Meanwhile, contrast-enhanced ultrasound
      (CEUS) has been established as a viable, fast and cost-effective imaging
      alternative for the follow-up and the detection of endoleaks after EVAR with the
      additional benefit of being a real-time non-ionizing radiation examination and
      having comparable or even superior diagnostic performance. This review describes
      the use of CEUS for follow-up after EVAR and describes the most common
      pathologies.

PMID- 28511227
TI  - Tenosynovitis Evaluation Using Image Fusion and B-Flow - A Pilot Study on New
      Imaging Techniques in Rheumatoid Arthritis Patients.
AB  - Aim The aim of this study was to compare the assessment of tenosynovitis by
      ultrasound (US) and magnetic resonance imaging (MRI) using the image fusion
      technique and to investigate whether US B-flow imaging (BFI) is an alternative to
      Doppler US when assessing tenosynovitis. Materials and Methods 15 patients with
      rheumatoid arthritis (RA) had US-verified tenosynovitis in the wrist/hand. An MRI
      was performed of the wrist/hand with subsequent repeated US and image fusion.
      Images were compared in three steps: 1. Visual image comparison, 2. Quantitative
      measurement of transverse areas of the affected tendon and tendon sheath, using
      two tendon measures on MRI, area 1 and area 2, excluding and including partial
      volume artifacts, respectively, 3. Assessment using the OMERACT semi-quantitative
      scoring systems for US and MRI. Furthermore, BFI was assessed as: 0: No flow, 1:
      Focal flow, 2: Multifocal flow, 3: Diffuse flow, in the tendon sheath. Results
      The median areas on US and MRI (areas 1 and 2) were 0.16 cm2 (25;75 pctl: 0.10;
      0.25), 0.9 cm2 (0.06; 0.18) and 0.13 cm2 (0.10; 0.25), respectively, for included
      tendons and 0.18 cm2 (0.13; 0.26), 0.27 cm2 (0.20; 0.45) and 0.23 cm2 (0.16;
      0.40) for tendon sheaths. No statistically significant difference was found
      between US tendon area and MRI tendon area 2 (Wilcoxon's test; p = 0.47).
      Overall, the agreement between grayscale and color Doppler (CD) US and MRI
      tenosynovitis visualization and scoring was good, but not between CD and BFI.
      Conclusion US and MRI have high agreement using image fusion for the assessment
      of tenosynovitis when partial volume artifacts are taken into account. BFI is not
      an alternative to CD for the measurement of slow flow in tenosynovitis.

PMID- 28511228
TI  - The 100 Most-Cited Articles Focused on Ultrasound Imaging: A Bibliometric
      Analysis.
AB  - Purpose The number of citations that an article has received reflects its impact
      on a particular research area. The aim of this study was to identify the 100 most
      cited articles focused on ultrasound (US) imaging and to analyze the
      characteristics of these articles. Methods We determined the 100 most-cited
      articles on US imaging via the Web of Science database, using the search term.
      The following parameters were used to analyze the characteristics of the 100 most
      cited articles: publication year, journal, journal impact factor, number of
      citations and annual citations, authors, department, institution, country, type
      of article, and topic. Results The number of citations for the 100 most-cited
      articles ranged from 1849 to 341 (median: 442.0) and the number of annual
      citations ranged from 108.0 to 8.1 (median: 22.1). The majority of articles were
      published in 1990 - 1999 (39 %), published in radiology journals (20 %),
      originated in the United States (45 %), were clinical observation studies (67 %),
      and dealt with the vessels (35 %). The Department of Internal Medicine at the
      University of California and the Research Institute of Public Health at the
      University of Kuopio (n = 4 each) were the leading institutions and Salonen JT
      and Salonen R (n = 4 each) were the most prolific authors. Conclusion Our study
      presents a detailed list and analysis of the 100 most-cited US articles, which
      provides a unique insight into the historical development in this field.

PMID- 28511230
TI  - [Papillary cystadenoma: a rare differential diagnosis of a paratesticular
      tumour].
AB  - Testicular and paratesticular cystadenomas arise from an oviduct-like structure,
      which, morphologically, is almost identical with the ovarian surface epithelium.
      These are very rare benign tumours of adults. They present as asymptomatic cystic
      lesions. Bilateral paratesticular cystadenomas are associated with the Von-Hippel
      Lindau syndrome and may be associated with infertility. Most cystadenomas are
      benign, but a few cases of malignant transformation of embryonic remnants have
      been reported in the appendix testis, including cases of adenocarcinoma,
      cystadenocarcinoma, and a Mullerian-type epithelial tumour with a low malignant
      potential. We report the case of a 74-year-old man with a rare paratesticular
      cystadenoma of the male adnexa.

PMID- 28511232
TI  - [Priapism in children and adolescents].
AB  - Priapism is a prolonged erection without sexual stimulation. In most cases it
      requires prompt management in order to avoid long-term consequences such as
      erectile dysfunction or penile deformity. Priapism is rare in children, but
      haematological diseases play an important role. The diagnosis is generally not
      difficult. Blood gas analysis and Doppler sonography are used to establish the
      form of priapism and determine its further management. The management of low-flow
      priapism consists of immediate blood aspiration and intracavernosal injection of
      sympathomimetic drugs as needed. In case of treatment failure, a shunt is also
      necessary. High-flow priapism generally does not require any immediate treatment.
      X-ray-assisted selective embolisation in case of fistula is associated with a
      high success rate. The primary aim in stuttering priapism is reduction and
      prophylaxis of erections and patient education about the disease. Penile
      prostheses are not used in children.

PMID- 28511229
TI  - HPLC-Based Activity Profiling for GABAA Receptor Modulators in Searsia pyroides
      Using a Larval Zebrafish Locomotor Assay.
AB  - A dichloromethane extract from leaves of Searsia pyroides potentiated gamma
      aminobutyric acid-induced chloride currents by 171.8 +/- 54% when tested at 100
      ug/mL in Xenopus oocytes transiently expressing gamma aminobutyric acid type A
      receptors composed of alpha1beta2gamma2s subunits. In zebrafish larvae, the
      extract significantly lowered pentylenetetrazol-provoked locomotion when tested
      at 4 ug/mL. Active compounds of the extract were tracked with the aid of HPLC
      based activity profiling utilizing a previously validated zebrafish larval
      locomotor activity assay. From two active HPLC fractions, compounds 1 - 3 were
      isolated. Structurally related compounds 4 - 6 were purified from a later eluting
      inactive HPLC fraction. With the aid of 1H and 13C NMR and high-resolution mass
      spectrometry, compounds 1 - 6 were identified as analogues of anacardic acid.
      Compounds 1 - 3 led to a concentration-dependent decrease of pentylenetetrazol
      provoked locomotion in the zebrafish larvae model, while 4 - 6 were inactive.
      Compounds 1 - 3 enhanced gamma aminobutyric acid-induced chloride currents in
      Xenopus oocytes in a concentration-dependent manner, while 4 - 6 only showed
      marginal enhancements of gamma aminobutyric acid-induced chloride currents.
      Compounds 2, 3, and 5 have not been reported previously.

PMID- 28511231
TI  - [Epididymitis in Children: Fact or Fiction].
AB  - Epididymitis is one of the most frequent causes of acute scrotum during
      childhood. Unlike in adults, ascending bacterial infections are rarely the
      underlying cause of the condition in children. Antibacterial treatment in
      accordance with a prior antibiogram is possible in the presence of leukocyturia
      and significant bacteriuria. For the remaining cases, there are no definite
      criteria allowing for a decision on acute antibacterial treatment. The fact that
      antibacterial treatment is still initiated in cases of epididymitis in the
      clinical routine setting is based on the assumption of a possible infection
      rather than being based on facts. This dilemma will probably not be entirely
      resolved until adequate diagnostic markers for the different trigger mechanisms
      of epididymitis have been found.

PMID- 28511233
TI  - [Diagnostic Imaging in Cases of Acute Scrotum].
AB  - Acute scrotum is one of the most common urologic emergencies in children and
      adolescents. This condition involves acute testicular pain, which is often
      accompanied by scrotal swelling and erythema. It is most important to distinguish
      between cases that require immediate surgery and those that can be treated
      conservatively. As patient history and physical findings may not always be
      unequivocal, ultrasound with Colour-Coded Doppler Sonography is the imaging
      modality of choice for further evaluation. Testicular torsion and other
      differential diagnoses such as epididymitis, appendiceal torsion, intratesticular
      haematoma after trauma, or complicated inguinal hernia have to be considered.
      Other imaging modalities such as MRI, scintigraphy and contrast-enhanced
      ultrasound are only necessary if the diagnosis remains unclear or if
      complications occur during the course of disease.

PMID- 28511234
TI  - Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided
      sampling in gastroenterology: European Society of Gastrointestinal Endoscopy
      (ESGE) Clinical Guideline - Updated January 2017.
AB  - For pancreatic solid lesions, ESGE recommends performing endoscopic ultrasound
      (EUS)-guided sampling as first-line procedure when a pathological diagnosis is
      required. Alternatively, percutaneous sampling may be considered in metastatic
      disease.Strong recommendation, moderate quality evidence.In the case of negative
      or inconclusive results and a high degree of suspicion of malignant disease, ESGE
      suggests re-evaluating the pathology slides, repeating EUS-guided sampling, or
      surgery.Weak recommendation, low quality evidence.In patients with chronic
      pancreatitis associated with a pancreatic mass, EUS-guided sampling results that
      do not confirm cancer should be interpreted with caution.Strong recommendation,
      low quality evidence.For pancreatic cystic lesions (PCLs), ESGE recommends EUS
      guided sampling for biochemical analyses plus cytopathological examination if a
      precise diagnosis may change patient management, except for lesions <= 10 mm in
      diameter with no high risk stigmata. If the volume of PCL aspirate is small, it
      is recommended that carcinoembryonic antigen (CEA) level determination be done as
      the first analysis.Strong recommendation, low quality evidence.For esophageal
      cancer, ESGE suggests performing EUS-guided sampling for the assessment of
      regional lymph nodes (LNs) in T1 (and, depending on local treatment policy, T2)
      adenocarcinoma and of lesions suspicious for metastasis such as distant LNs, left
      liver lobe lesions, and suspected peritoneal carcinomatosis.Weak recommendation,
      low quality evidence.For lymphadenopathy of unknown origin, ESGE recommends
      performing EUS-guided (or alternatively endobronchial ultrasound [EBUS]-guided)
      sampling if the pathological result is likely to affect patient management and no
      superficial lymphadenopathy is easily accessible.Strong recommendation, moderate
      quality evidence.In the case of solid liver masses suspicious for metastasis,
      ESGE suggests performing EUS-guided sampling if the pathological result is likely
      to affect patient management, and (i) the lesion is poorly accessible/not
      detected at percutaneous imaging, or (ii) a sample obtained via the percutaneous
      route repeatedly yielded an inconclusive result.Weak recommendation, low quality
      evidence.

PMID- 28511235
TI  - Direct peroral cholangioscopy with a new anchoring technique using the guide
      probe of Kautz - first clinical experiences.
AB  - Background and study aims We present the first clinical results of a new tandem
      technique for direct peroral cholangioscopy using a standard ultraslim upper
      gastrointestinal endoscope and a guide probe that was originally developed for
      the non-transendoscopic placement of biliary endoprostheses (guide probe of
      Kautz; MTW, Wesel, Germany). Patients and methods Twenty direct peroral
      cholangioscopy procedures were performed with the new anchor-assisted method
      using the guide probe of Kautz in a single center and were retrospectively
      analyzed. Results  Indications for anchor-assisted cholangioscopy procedures
      included indeterminate bile duct strictures (n = 14), filling defects that
      remained after stone extraction (n = 4), and complex stone extractions (n = 2).
      Biliary access and visualization of the target region were achieved in 18/20
      procedures (90 %). The interventional success rate was 85 % (11 /13
      interventions). One case of postinterventional cholangitis occurred (5 %), along
      with one case of minor peri-interventional papillary bleeding (5 %). Conclusions
      The anchor-assisted cholangioscopy technique is feasible and safe for direct
      cholangioscopy and provides reliable success rates in clinical practice. This
      technique represents an alternative approach for direct cholangioscopy on a
      single-operator basis using standard endoscopes.

PMID- 28511236
TI  - Long-term outcomes after endoscopic ultrasound-guided ablation of pancreatic
      cysts.
AB  - Background and study aims The aim of this study was to investigate the long-term
      outcomes after endoscopic ultrasound (EUS)-guided pancreatic cyst ablation.
      Patients and methods In a single-center, prospective study, 164 patients with
      pancreatic cysts underwent EUS-guided cyst ablation using ethanol with
      paclitaxel. The inclusion criteria were as follows: unilocular or oligolocular
      cysts; clinically indeterminate cysts that required EUS fine-needle aspiration;
      and/or cysts that grew during the observation period. Treatment response was
      classified as complete resolution, partial resolution, or persistent cyst, with <
      5 %, 5 % - 25 %, and 25 % of the original cyst volume, respectively. Results The
      median largest diameter of the cyst was 32 mm and the median volume was 17.1 mL.
      Based on cyst fluid analysis there were 71 mucinous cystic neoplasms, 16 serous
      cystic neoplasms, 11 intraductal papillary mucinous neoplasms, 3 pseudocysts, and
      63 indeterminate cysts. Sixteen treated patients (9.8 %) had adverse events (1
      severe, 4 moderate, and 11 mild). Treatment response was as follows: complete
      resolution in 114 (72.2 %), partial resolution in 31 (19.6 %), and persistent
      cysts in 13 (8.2 %). Twelve of the 13 patients with persistent cysts underwent
      surgery. During clinical and imaging follow-up (median 72 months, interquartile
      range 50 - 85 months) of the 114 patients with complete resolution, only two
      patients (1.7 %) showed cyst recurrence. Based on multivariate analysis, the
      absence of septa (odds ratio [OR] 7.12, 95 % confidence interval [CI] 2.72 -
      18.67) and cyst size less than 35 mm (OR 2.39, 95 %CI 1.11 - 5.16) predicted
      complete resolution. Conclusion Among patients with pancreatic cysts in whom
      complete resolution was achieved after EUS-guided cyst ablation, 98.3 % remained
      in remission at 6-year follow-up. Unilocular form and small cyst size were
      predictive of complete resolution. This treatment approach may be an effective
      and durable alternative to surgery.Trial registered at ClinicalTrials.gov (NCT
      00689715).

PMID- 28511237
TI  - Performance of a fully disposable, digital, single-operator
      cholangiopancreatoscope.
AB  - Background and study aim Our aim was to evaluate the first use in humans of a
      new, single-use, digital, single-operator intraductal cholangiopancreatoscopy
      system (IDCP). Patients and methods Data were collected retrospectively from four
      US institutions between February 2015 and April 2015. The visual impression of
      neoplasia or benign findings with IDCP was determined by the performing
      endoscopist. High grade dysplasia, intraductal papillary mucinous neoplasm,
      neuroendocrine tumor, and malignancy were categorized as neoplasia. Benign
      disease was defined as the absence of neoplasia during >= 6 months of follow-up.
      Results Patients (n = 108) with indeterminate strictures, dilatation, or
      difficult stones underwent IDCP. Of 74 patients with indeterminate stricture or
      dilatation, 29 (39 %) had neoplasia, of which 25 were confirmed by miniature
      biopsy forceps, 2 by surgical pathology, and 2 by the presence of metastatic
      disease on follow-up imaging. In patients with benign disease, 15 had concentric
      stenosis or normal/erythematous changes, 5 had low papillary mucosal projections,
      6 had coarse granular mucosa, and 4 had nodular mucosa. Findings in patients with
      neoplastic disease included dilated, tortuous vessels ("tumor vessels"; n = 13),
      irregular margins with partial occlusion of the lumen (infiltrative stricture, n
      = 12), villous or nodular mass (n = 9), and finger-like villiform projections (n
      = 5). Operating characteristics for indeterminate stricture or dilatation were:
      97 % sensitivity, 93 % specificity, 90 % positive predictive value, 98 % negative
      predictive value. Targeted biopsy yielded 86 % sensitivity and 100 % specificity.
      Stone clearance was noted in all cases. Adverse events occurred in 3 %.
      Conclusion The new IDCP system provides enhanced image resolution, and may
      improve the ability to target difficult stones and diagnose indeterminate
      strictures.

PMID- 28511238
TI  - [Subjective Adverse Effects during Outpatient CBT: Associations to Patient and
      Therapist Variables and to the Therapeutic Alliance].
AB  - Background Empirical data on variety, frequency, and prerequisites for unwanted
      side effects of psychotherapies are important regarding the planning,
      realization, and quality assurance of treatment. The study describes adverse
      effects of outpatient psychotherapy treatment and their association with patient,
      therapist and treatment characteristics. Methods To reduce memory bias, 70
      outpatient psychotherapy patients fulfilled the Inventory for the Assessment of
      Negative Effects of Psychotherapy (INEP). Data on patients' characteristics (sex,
      age, impairment), therapists' sex, and therpeutic alliance were collected.
      Results 84 % percent of patients reported at least one unwanted side effect
      (range 1-13; m=3.4; sd=3.43). Patients, age, number and kind of pretreatments,
      and the quality of the therapeutic alliance were associated with the frequency of
      unwanted negative effects. Discussion Unwanted side effects during outpatient
      psychotherapy are common phenomena and need careful attention in patient
      education and during the treatment itself.

PMID- 28511239
TI  - [Importance of Work and Employment in the Treatment of People with Mental Illness
      - Results of a Qualitative Study].
AB  - Exclusion of individuals with mental disorders is common, especially exclusion
      from the work force. This paper investigates the role of work and the
      reintegration into the workforce of patients with mental illness from the mental
      health professional's perspective. Within a qualitative study design, 44 mental
      health professionals from different settings and regions in Germany were
      interviewed. The material was transcribed verbatim and a content analysis was
      conducted. It can be shown that work and inclusion in the workforce is an
      important topic and that occupational status is discussed early in the treatment
      process. However, the roles of mental health professionals in different settings
      vary considerably. Within treatment settings, specific concepts and structured
      cooperation facilitating the reintegration of patients with mental illness into
      the workforce are largely lacking.

PMID- 28511240
TI  - [Treatment Outcome in Female In-Patients with Anorexia nervosa and Comorbid
      Personality Disorders Prevalence - Therapy Drop out and Weight Gain].
AB  - Introduction Personality disorders (PD) are among the most common comorbid
      disorders in female patients with Anorexia Nervosa (AN). Recent research findings
      suggest that comorbid PD are associated with a higher treatment drop-out rate and
      a worse therapeutic outcome. However, no study to date has distinguished between
      certain age groups concerning these issues. Research questions Therefore, the
      present study focuses on the prevalence of PD (1), treatment drop-out rates (2)
      and weight gain (3) in female in-patients with AN. Thereby, we differentiate
      among three age groups (17-24 years; 25-34 years; 35-65 years). Material &
      Methods We assessed female in-patients (N=331) with AN at the Helios Clinic in
      Bad Gronenbach in Germany using the Eating Disorders Inventory-2 and the
      psychotherapeutic-medical basic documentation at the beginning and at the end of
      their treatment. Furthermore, we investigated the drop-out rate and weight gain
      by comparing anorexic patients with and without comorbid PD that were diagnosed
      by clinicians using ICD-10 criteria. Results In sum, our patients with AN
      demonstrated a prevalence rate of 34% for one or more comorbid PD. Interestingly,
      patients between 17-24 years showed a lower prevalence rate of 22% compared to
      those between 25-34 years (42%) and 35-65 years (41%). Furthermore, younger age
      and comorbid PD seemed to be significant predictors for treatment dropout. One of
      the most striking results was that younger patients (17-24) without a comorbid PD
      had the highest weight gain during treatment. This could not be observed in
      patients with a comorbid PD, who demonstrated the highest weight gain between 25
      and 34 years of age. Conclusion Our findings support the hypothesis that comorbid
      PD are related to a worse outcome in patients with eating disorders. Future
      studies might do well in assessing dimensional scores of personality disorders
      and other relevant aspects like for example the amount of social support to draw
      further conclusions on these associations. Our results emphasize the need for
      more disorder-specific interventions tailoring at patients with AN and comorbid
      PD to improve treatment outcome.

PMID- 28511241
TI  - [Short- and Mid-Term Effectiveness of Primary and Secondary Prevention of
      Comorbid Depressive Symptoms among Patients with Chronic Low Back Pain].
AB  - Background Because of high rates of comorbid mental disorders among patients with
      chronic low back pain, an intervention for pain competence and depression
      prevention for multidisciplinary inpatient rehabilitation was newly developed and
      evaluated concerning depressive symptoms, anxiety and pain related parameters.
      Methods Per protocol regression analyses with data of n=723 patients were
      conducted to evaluate the intervention. Intraindividual changes were quantified
      by Cohen's d based on repeated measures analyses of variance. The results of the
      regression analyses were validated by n=1306 multiple imputed data. Results
      Patients benefited in all analyzed parameters in the short- and mid-term (6
      months after intervention) from the rehabilitation with as well as without
      supplemental depression prevention training. Depressive symptoms in the beginning
      of the rehabilitation were a significant predictor for all analyzed parameters.
      Additionally, the depression prevention training reduced the lowest pain
      intensity in the short-term independent from depressive symptoms. The results
      were confirmed by analyses with multiple imputations. However, improvements
      declined especially in depressive symptoms and anxiety in the months after
      rehabilitation. Discussion The results support the influence of depressive
      symptoms on psychological and pain related parameters, which emphasizes the
      relevance of an early treatment of depressive symptoms. Though, the supplemental
      depression prevention training had no additional effect in the inpatient
      rehabilitation setting, which could be explained by the high effect sizes of the
      sole pain competence training. Moreover, beneficial effects should be supported
      by aftercare, because effects declined during the 6 months after rehabilitation.

PMID- 28511242
TI  - [Depression and Comorbid Personality Disorder - Effectiveness of Psychodynamic
      Inpatient Psychotherapy].
AB  - Objectives Depression is one of the most common illnesses. The effectiveness of
      psychodynamic psychotherapy on depressive symptom load has been demonstrated.
      However, for patients suffering from comorbid personality disorder (PD) a
      decreased benefit has been reported, as well as fewer rates of remission and
      extended duration of remission. However, findings are inconsistent. The objective
      of this study was to determine potential differences in therapy-outcome comparing
      female patients with and without comorbid PD. Method Including female inpatients
      aged between 25-45 years (N=377) in a psychodynamic treatment, the dissenting
      outcome on depressive symptom load (among others BDI; HAMD) as well as
      psychodynamic variables (IPO) by patients with and without comorbid PD were
      analysed within a naturalistic multicenter intervention study (STOP-D). Data were
      collected in 15 psychodynamically oriented psychosomatic hospital units in
      Germany, based on self- and external-assessment instruments. Results Under
      comparable therapy-doses, female patients with and without comorbid PD benefit
      significantly from psychodynamic inpatient treatment. By equivalent baseline
      severity of clinical symptoms patients without comorbid PD show larger effect
      sizes in all inventories than patients with comorbid PD. Discussion Although the
      benefit is lower for depressed patients with comorbid personality disorder, the
      positive effect of inpatient psychodynamic psychotherapy is statistically and
      clinically significant in both groups. Influences of further comorbid symptoms
      and confounding symptoms between depression and PD, which were difficult to
      control, are possible. Further studies are necessary. Conclusion Although
      patients with comorbid PD benefit significantly from the inpatient treatment, a
      special therapeutic design seems to be indicated for these patients.

PMID- 28511243
TI  - [Emotional Arousal (Voice Stress) and Posttraumatic Growth as well as
      Relationship Satisfaction of Partners of Women with Breast Cancer in the Context
      of Social Support].
AB  - Introduction Breast cancer is associated with significant psychosocial strains
      for both patients and partners. Constructive social support and positive
      communication behavior have been shown to be protective against the burdens
      associated with breast cancer. Individual levels of emotional arousal during
      social support interactions with one's spouse are an important aspect of couples'
      support behaviors and can be assessed via vocal fundamental frequency (f0).
      Methods N=44 couples had standardized seven-minute long interactions asking the
      male partner to describe his thoughts and feelings with regard to their wives'
      breast cancer. Using actor-partner interdependence models (APIM), f0's
      associations with individual posttraumatic growth (PTG) and perceived marital
      quality were differentially investigated. Results Significant actor effects for
      f0 and PTG were found for both husbands as well as tendencies for partner effects
      and wives. Perceived marital quality was not significantly associated with one's
      own levels of emotional arousal. No significant partner effects emerged for any
      of the variables of interest. Discussion Contrary to findings in couples'
      conflict discussions, higher levels of emotional arousal in social support
      interactions are associated with positive aspects of psychological functioning.
      F0 during social support could be associated with higher levels of self-efficacy,
      which might be beneficial for PTG and constructive ways of emotional expression.
      Constructive expression of emotional arousal could lead to heightened involvement
      in support interactions and may be voiced via higher levels of f0. Further
      analyses to replicate these findings are necessary.

PMID- 28511244
TI  - Survival and Long-Term Outcomes of Aortic Valve Replacement in Patients Aged 55
      to 65 Years.
AB  - BACKGROUND: This study aims to compare the outcomes after aortic valve
      replacement (AVR) with mechanical and biological valves in middle-aged patients
      (55-65 years) to determine the impact on long-term mortality and morbidity.
      METHODS: A retrospective analysis of 373 patients between 55 and 65 years of age
      who received a primary AVR with or without concomitant coronary artery bypass
      graft between April 1995 and March 2014. Propensity matching yielded 118 patient
      pairs in the mechanical and biological valve cohorts. RESULTS: Median follow-up
      time was 6.9 years. No differences in long-term survival or a composite outcome
      of stroke, bleeding, and endocarditis (major adverse prosthesis-related event;
      MAPE) were observed in patients receiving biological versus mechanical valves.
      Actuarial 15-year survival was 46.4% (95% confidence interval [CI], 28.8-62.3%)
      in the biological valve group versus 60.6% (95% CI, 47.5-71.4%) in the mechanical
      valve group (hazard ratio, 1.16 [95%CI, 0.69-1.94], p = 0.58). The 15-year
      cumulative incidence of MAPE was 53.3% (95% CI, 33.7-69.4%) for biological valves
      versus 24.5% (95% CI, 16.2-33.8%) for mechanical valves (hazard ratio, 0.65 [95%
      CI, 0.37-1.14], p = 0.12). The 15-year cumulative incidence of reoperation was
      higher in the bioprosthetic group (26.0% [95% CI, 14.0-39.8%] vs. 5.4% [95% CI,
      2.0-11.4%]; hazard ratio 0.24 [95% CI, 0.09-0.68] p < 0.01). CONCLUSION: There is
      no difference in survival and MAPE at 15 years between biological and mechanical
      valves. The risk of reoperation was significantly higher in the biological valve
      group and may affect valve choice in middle-aged patients.

PMID- 28511245
TI  - Low Fibrinogen Is Associated with Increased Bleeding-Related Re-exploration after
      Cardiac Surgery.

PMID- 28511246
TI  - Early Postoperative Endoscopy for Evaluation of the Anastomosis after Esophageal
      Reconstruction.
AB  - BACKGROUND: Anastomotic leaks significantly affect hospital stay after esophageal
      surgery. Here, we investigated the efficacy of early endoscopy for predicting
      anastomotic healing and leaks after esophageal reconstruction. METHODS: A total
      of 65 consecutive esophageal cancer patients treated by cervical
      esophagogastrostomy underwent routine endoscopy between postoperative days 5 and
      7. The anastomosis was scored for the degree of ischemia, stenosis, and torsion
      of the anastomotic axis. Independent associations between ischemia, stenosis, and
      torsion of the proximal esophagus and the risk of the anastomotic leak were
      examined using Spearman's rank correlation method. RESULTS: Assessment of the
      degree of mucosal ischemia in 65 patients shows well healing in 35, patch
      ischemia in 20, diffuse ischemia in 10, no necrosis in any patient. Stenosis was
      classified as 0 to 10% in 40 patients, 11 to 20% in 12, 21 to 80% in 11, and 81
      to 100% in 2. The degree of torsion of the anastomotic axis was classified as 0
      to 10 degrees in 52 patients, 11 to 90 degrees in 8, and 91 to 180 degrees in 5.
      With rising endoscopy scores, there was an increase in risk for leaks (score >
      4.5, sensitivity 100%, and specificity 83.8%). CONCLUSIONS: Early postoperative
      endoscopy facilitates the management of esophagogastrostomy anastomosis to
      predict leaks.

PMID- 28511248
TI  - The Importance of Facts and the Role of Academic Publishers in Today's World-A
      Publisher's View.

PMID- 28511247
TI  - Cardiac Surgeons after Vacation: Refreshed or Rusty?
AB  - Introduction: Many surgeons describe feeling a bit out of practice when they
      returnfrom a vacation. There have been no studies assessing the impact of surgeon
      vacationon patient outcomes. Methods: We used administrative data from the
      province of Ontario to identifypatients who underwent a coronary artery bypass
      grafting. Using a propensity score,we matched patients who underwent their
      procedure immediately after their surgeonreturned from vacation of at least 7
      days (n = 1,161) to patients who were notoperated immediately before or after a
      vacation period (n = 2,138). Results: There was no significant difference in
      patient mortality (odds ratio: 1.23,p = 0.52), length of operation (relative risk
      [RR]: 1.00 p = 0.58), or intensive care unit/hospital stay (RR: 0.97 p = 0.66/RR:
      0.98 p = 0.54, respectively). Conclusion: There was not a significant change in
      risk of death, operative length, orhospital stay after a surgeon vacation.

PMID- 28511249
TI  - Christopher W. Hess, MD, and Michael S. Okun, MD.

PMID- 28511250
TI  - Update on Parkinson's Disease.

PMID- 28511252
TI  - Diagnosis and Management of Parkinson's Disease.
AB  - Despite numerous efforts to identify specific and sensitive biomarkers, the
      diagnosis of Parkinson's disease (PD) is still based on clinical criteria that
      include the presence of a combination of cardinal motor features (tremor,
      rigidity, bradykinesia, and postural instability), other motor features
      (including freezing of gait and abnormal postures), and numerous nonmotor
      features. In addition, the presence of atypical features may suggest an
      alternative diagnosis. Levodopa therapy remains the gold standard in the
      management of motor features of PD. New formulations of levodopa and novel
      delivery systems are currently being evaluated and gradually introduced in
      clinical practice in an attempt to prevent or treat levodopa-related motor
      complications. Dopamine agonists also play an important role as monotherapy in
      mild or adjunctive therapy in moderately advanced disease. As the disease
      progresses and patients develop complications from levodopa therapy, specifically
      motor fluctuations and dyskinesias, deep brain stimulation becomes an alternative
      therapeutic option. Clinical trials of experimental therapeutics are currently
      fueling the PD therapeutic pipeline.

PMID- 28511253
TI  - Pathophysiology and Management of Parkinsonian Tremor.
AB  - Parkinson's tremor is one of the cardinal motor symptoms of Parkinson's disease.
      The pathophysiology of Parkinson's tremor is different from that of other motor
      symptoms such as bradykinesia and rigidity. In this review, the authors discuss
      evidence suggesting that tremor is a network disorder that arises from distinct
      pathophysiological changes in the basal ganglia and in the
      cerebellothalamocortical circuit. They also discuss how interventions in this
      circuitry, for example, deep brain surgery and noninvasive brain stimulation, can
      modulate or even treat tremor. Future research may focus on understanding sources
      for the large variability between patients in terms of treatment response, on
      understanding the contextual factors that modulate tremor (stress, voluntary
      movements), and on focused interventions in the tremor circuitry.

PMID- 28511251
TI  - The Phenomenology of Parkinson's Disease.
AB  - The motor symptoms of Parkinson's disease are not limited to the cardinal
      symptoms of bradykinesia, rigidity, and resting tremor, but also include a
      variety of interrelated motor phenomena such as deficits in spatiotemporal
      planning and movement sequencing, scaling and timing of movements, and
      intermuscular coordination that can be clinically observed. Although many of
      these phenomena overlap, a review of the full breadth of the motor phenomenon can
      aid in the diagnosis and monitoring of disease progression.

PMID- 28511254
TI  - Genetic Forms of Parkinson's Disease.
AB  - One of the greatest advances in Parkinson's disease (PD) research in the past two
      decades has been a better understanding of PD genetics. Of the many candidate
      genes investigated, the best studied include LRRK2, SNCA, VPS35, Parkin, PINK1,
      and DJ1. The authors review the key clinical features of these monogenic forms,
      as well as for the prevalent risk factor gene, GBA, including the phenotype,
      clinical course, and treatment response. They also outline areas for future
      investigation: longitudinal studies of PD's clinical course, the identification
      of its premotor manifestations, and its specific mechanisms of pathogenicity.

PMID- 28511256
TI  - Nonmotor Symptoms in Parkinson's Disease.
AB  - Nonmotor symptoms (NMSs) in Parkinson's disease (PD) have become increasingly
      recognized as major determinants of quality of life across cultures worldwide.
      Behavioral symptoms include dementia, depression, anxiety, apathy, and fatigue.
      Somatic symptoms include hypotension, constipation, diaphoresis, and pain.
      However, somatic symptoms may also be intrinsic, such as dementia, and
      iatrogenic, such as compulsive disorders. The authors address some of the more
      common disorders, yet few have been the target of clinical trials.

PMID- 28511257
TI  - Characterizing Cognitive Impairment in Parkinson's Disease.
AB  - Cognitive impairment is a frequent complication in Parkinson's disease (PD),
      though it can be heterogeneous in its presentation and progression. Cognitive
      deficits vary among patients with regard to clinical features, severity, and
      progression to dementia. A growing recognition of cognitive impairment in PD in
      both the clinical and research settings has led to advances in diagnostic
      criteria and improved understanding of the clinical phenotypes, associated
      biomarkers, and underlying pathophysiology of both PD dementia and PD mild
      cognitive impairment. Therapeutic interventions are geared to improve symptoms
      and ideally to prevent cognitive decline. Here the authors summarize the current
      research on the characterization of cognitive impairment in PD, with specific
      attention focused on its clinical phenotype, associated neuropsychiatric and
      prodromal features, pathological changes, genetic variations, and imaging and
      biochemical biomarkers.

PMID- 28511258
TI  - Management of Autonomic Dysfunction in Parkinson's Disease.
AB  - Autonomic dysfunction is a frequent and important nonmotor feature of Parkinson's
      disease (PD). Autonomic dysfunction in PD spans a broad clinical spectrum.
      Cardiovascular dysfunction is characterized most prominently by orthostatic
      hypotension. Gastrointestinal dysfunction can involve virtually all levels of the
      gastrointestinal tract. Urinary dysfunction can entail either too frequent
      voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for
      both the patient and the partner. Alterations in sweating and body temperature
      are not widely recognized, but often are present. The presence of effective
      treatment for at least some aspects of autonomic dysfunction makes it vitally
      important that the assessment of autonomic dysfunction be a regular component of
      the neurologic history and examination for individuals with PD.

PMID- 28511255
TI  - Motor Complications of Dopaminergic Medications in Parkinson's Disease.
AB  - Motor complications are a consequence of the chronic treatment of Parkinson's
      disease (PD) and include motor fluctuations (wearing-off phenomenon) and levodopa
      induced dyskinesia. Both can have a significant impact on functionality and
      quality of life; thus, proper recognition and management is essential. The
      phenomenology and temporal relationship of motor complications to the schedule of
      levodopa dosing can be helpful in characterizing them. There are several
      therapeutic approaches to motor complications, including pharmacological and
      surgical options. The authors summarize the different types of motor
      complications according to phenomenology and the currently available medical
      treatments, including ongoing trials for the management of this condition.

PMID- 28511260
TI  - Botulinum Toxin Therapy for Parkinson's Disease.
AB  - Botulinum toxin (BoNT) therapy is frequently employed in the treatment of
      Parkinson's disease (PD) symptoms. It can effectively ameliorate the symptoms of
      cervical dystonia, blepharospasm, sialorrhea, and hyperactive bladder. It is
      increasingly being used for additional PD-related indications including limb
      dystonia, oromandibular dystonia, tremors, constipation, dysphagia,
      gastroparesis, and sweating dysfunction. Botulinum toxin treatment has mostly
      local side effects and does not interfere with dopaminergic therapies prescribed
      for PD. With the exception of dystonia and sialorrhea, most evidence for BoNT
      efficacy is derived from studies conducted in nonparkinsonian populations. Thus,
      the data to inform typical response pattern and side-effect profile in PD are
      still evolving. Nevertheless, BoNT is widely used and is an important tool in the
      PD-treatment arsenal. In this review, the authors discuss the current literature
      on the use of BoNT in various PD-related motor and nonmotor disorders.

PMID- 28511259
TI  - Impulse Control Disorders and Related Complications of Parkinson's Disease
      Therapy.
AB  - Impulsive and compulsive behaviors in Parkinson's disease (PD) patients are most
      often attributed to dopamine agonist therapy; dysregulation of the
      mesocorticolimbic system accounts for this behavioral phenotype. The clinical
      presentation is commonly termed impulse control disorder (ICD): Behaviors include
      hypersexuality, compulsive eating, shopping, pathological gambling, and
      compulsive hobby participation. However, not all PD individuals taking dopamine
      agonists develop these behavioral changes. In this review, the authors focus on
      the similarities between the phenotypic presentation of ICDs with that of other
      reward-based behavioral disorders, including binge eating disorder, pathological
      gambling, and substance use disorders. With this comparison, we emphasize that
      the transition from an impulsive to compulsive behavior likely follows a ventral
      to dorsal striatal pattern, where an altered dopaminergic reward system underlies
      the emergence of these problematic behaviors. The authors discuss the
      neurobiological similarities between these latter disorders and ICDs, emphasizing
      similar pathophysiological processes and discussing treatment options that have
      potential for translation to PD patients.

PMID- 28511261
TI  - Current Practice and the Future of Deep Brain Stimulation Therapy in Parkinson's
      Disease.
AB  - Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease
      patients experiencing motor fluctuations, medication-resistant tremor, and/or
      dyskinesia. Currently, the subthalamic nucleus and the globus pallidus internus
      are the two most widely used targets, with individual advantages and
      disadvantages influencing patient selection. Potential DBS patients are selected
      using the few existing guidelines and the available DBS literature, and many
      centers employ an interdisciplinary team review of the individual's risk-benefit
      profile. Programmed settings vary based on institution- or physician-specific
      protocols designed to maximize benefits and limit adverse effects. Expectations
      should be realistic and clearly defined during the evaluation process, and each
      bothersome symptom should be addressed in the context of building the risk
      benefit profile. Current DBS research is focused on improved symptom control, the
      development of newer technologies, and the improved efficiency of stimulation
      delivery. Techniques deliver stimulation in a more personalized way, and methods
      of adaptive DBS such as closed-loop approaches are already on the horizon.

PMID- 28511263
TI  - Diagnosis and Treatment of Functional (Psychogenic) Parkinsonism.
AB  - Functional (psychogenic) parkinsonism (FP) is recognized by the mandatory
      combination of marked slowness without progressive decrement on repetitive manual
      tasks and variable resistance against passive movements in the absence of
      cogwheel rigidity. Other functional phenotypes, such as functional tremor and
      functional gait impairment, may coexist. Although neither necessary nor
      sufficient for the diagnosis of FP, supportive historical clues include the
      sudden onset of symptoms and absent or nonphysiologic response to levodopa. In
      selected cases where examination features remain insufficient to render a
      clinically definite FP diagnosis, normal dopaminergic transporter imaging (DAT
      scan) confirms "laboratory supported" FP. The management of FP begins with
      diagnostic debriefing, as the full acceptance of the diagnosis is critical in
      ensuring patient involvement in individualized psychoeducation, psychotherapy,
      and physical and occupational therapy.

PMID- 28511262
TI  - Recognizing Atypical Parkinsonisms: "Red Flags" and Therapeutic Approaches.
AB  - The overlap of signs and symptoms between Parkinson's disease and the atypical
      parkinsonian syndromes, such as progressive supranuclear palsy, multiple system
      atrophy, corticobasal syndrome and dementia with Lewy bodies, can render clinical
      diagnoses challenging. The continued evolution of diagnostic criteria to reflect
      the increasingly recognized heterogeneous presentations of these diseases further
      complicates timely recognition and diagnosis. In this review, we provide a
      diagnostic approach to the classic atypical parkinsonian syndromes, with an
      emphasis on the key clinical and pathological features of each and the
      recognition of "red flags" in the setting of recent advances in diagnosis and
      treatment.

PMID- 28511264
TI  - Visceral Artery Aneurysms and Pseudoaneurysms: Retrospective Analysis of
      Interventional Endovascular Therapy of 43 Aneurysms.
AB  - Purpose To evaluate the results of interventional endovascular therapy of
      incidental and symptomatic visceral artery aneurysms in the elective and
      emergency situation. Materials and Methods 43 aneurysms in 38 patients (19
      female, 19 male, mean age: 57 +/- 16 years [18 - 82]) were treated between 2011
      and 2015. The characteristics of the aneurysms (true vs. false aneurysm, size,
      etiology, location, symptoms) were considered. Furthermore, we evaluated the
      intervention with respect to technical success, embolic/occlusive agents used,
      therapy-associated complications and post-interventional follow-up.  Results 23
      true aneurysms (maximum diameter: 22 +/- 18 mm [11 - 67 mm]) and 20 false
      aneurysms (maximum diameter: 9 +/- 33 mm [3 - 150 mm]) were evaluated. The
      splenic (n = 14) and renal arteries (n = 18) were most frequently affected. The
      etiology was most commonly degenerative-atherosclerotic (47 %) or iatrogenic post
      operative (19 %). 18/48 interventions were performed due to active bleeding.
      False aneurysms were associated significantly more often with active bleeding (63
      vs. 25 %, p = 0.012). 41/48 treatments were technically successful. Re
      intervention was necessary 6 times. In 2 cases the endovascular approach did not
      succeed. There was a complication rate of 10 %, whereby only 4 minor and 1 major
      complications occurred. No patient suffered from permanent sequelae. Aneurysms
      were primarily treated by using coils and if necessary additional embolic agents
      (liquid embolic agent or vascular plugs) (75 %). In the follow-up period,
      reperfusion of treated aneurysms occurred at a rate of 7 % (n = 3). Conclusion
      Interventional endovascular therapy of visceral artery aneurysms is safe and
      effective in the elective treatment of incidental aneurysms as well as in
      significantly more frequent hemorrhaging false aneurysms in the emergency
      situation. Key points  . Interventional endovascular therapy of visceral artery
      aneurysms is safe and effective.. . In more than 60 % of cases visceral artery
      pseudoaneurysms are associated significantly more often with a history of
      bleeding or acute bleeding. Hence, there is a need for (interventional) therapy
      even in small pseudoaneurysms.. . Follow-up seems to be useful to detect
      reperfusion as manifestation of treatment failure.. Citation Format . Ruhnke H,
      Kroncke TJ, . Visceral Artery Aneurysms and Pseudoaneurysms: Retrospective
      Analysis of Interventional Endovascular Therapy of 43 Aneurysms. Fortschr
      Rontgenstr 2017; 189: 632 - 639.

PMID- 28511265
TI  - Diagnostic Value of Diffusion-Weighted MRI for Tumor Characterization,
      Differentiation and Monitoring in Pediatric Patients with Neuroblastic Tumors.
AB  - Purpose We explored the diagnostic value of diffusion-weighted MRI (DWI) for
      tumor characterization, differentiation and therapy monitoring in pediatric
      patients with extracranial neuroblastic tumors. Materials and Methods All 29
      patients (14 girls, median age: 3 years) with neuroblastoma (NB, n = 19),
      ganglioneuroblastoma (GNB, n = 4) and ganglioneuroma (GN, n = 6) who had had at
      least one in-house DWI examination since 2005 were identified and retrospectively
      analyzed. Two independent blinded readers measured ADC values (unit: 10-3 mm2/s)
      and signal intensity ratios (SIRs) of the primary tumor and, if applicable, of
      the tumor after chemotherapy, metastases and tumor relapse. Results The pre
      treatment ADC was 0.90 +/- 0.23 in NB/GNB and 1.70 +/- 0.36 in GN without overlap
      between the two entities for both readers, 0.67 +/- 0.14 in metastases and 0.72
      +/- 0.18 in tumor relapse. With chemotherapy, mean ADC increased to 1.54 +/- 0.33
      in NB/GNB and to 1.23 +/- 0.27 in metastases (p < 0.05). The median SIRs of
      various tumor lesions vs. liver, vs. muscle tissue and vs. adjacent tissue were
      significantly higher on DWI (range: 2.4 - 9.9) than on ce-T1w (range: 1.0 - 1.8,
      all p < 0.05). The coefficient of variation (CV) was <= 8.0 % for ADC and <= 16.4
      % for signal intensity data. Conclusion Based on mean ADC, DWI distinguishes
      between NB/GNB and GN with high certainty and provides plausible quantitative
      data on tumor response to therapy. Lesion conspicuity, as measured by SIR, is
      superior on DWI, compared to ce-T1w. DWI as a noninvasive, radiation-free and
      widely available imaging technique should be an integral part of MR imaging for
      neuroblastic tumors and should undergo prospective evaluation in multicenter
      studies. Key Points  . DWI reliably distinguishes
      neuroblastoma/ganglioneuroblastoma from ganglioneuroma, based on the mean ADC.. .
      DWI provides plausible quantitative data on tumor response to chemotherapy.. .
      DWI offers highly superior lesion conspicuity compared to contrast-enhanced T1w
      imaging.. . DWI should be considered a standard for imaging neuroblastic tumors..
      Citation Format . Neubauer H, Li M, Muller VR et al. Diagnostic Value of
      Diffusion-Weighted MRI for Tumor Characterization, Differentiation and Monitoring
      in Pediatric Patients with Neuroblastic Tumors. Fortschr Rontgenstr 2017; 189:
      640 - 650.

PMID- 28511266
TI  - Diagnosis and Differential Diagnosis of Hydrocephalus in Adults.
AB  - Purpose Hydrocephalus is caused by an imbalance of production and absorption of
      cerebrospinal fluid (CSF) or obstruction of its pathways, resulting in
      ventricular dilatation and increased intracranial pressure. Imaging plays a
      crucial role in the diagnosis, differential diagnosis and planning of treatment.
      Methods This review article presents the different types of hydrocephalus und
      their typical imaging appearance, describes imaging techniques, and discusses
      differential diagnoses of the different forms of hydrocephalus. Results and
      Conclusion Imaging plays a central role in the diagnosis of hydrocephalus. While
      magnetic resonance (MR) imaging is the first-line imaging modality, computed
      tomography (CT) is often the first-line imaging test in emergency patients. Key
      points  . Occlusive hydrocephalus is caused by obstruction of CSF pathways.. .
      Malabsorptive hydrocephalus is caused by impaired CSF absorption.. . The MR
      imaging protocol should always include sagittal high-resolution T2-weighted
      images.. . When an inflammatory etiology is suspected, imaging with contrast
      agent administration is necessary.. Citation Format . Langner S, Fleck S, Baldauf
      J et al. Diagnosis and Differential Diagnosis of Hydrocephalus in Adults.
      Fortschr Rontgenstr 2017; 189: 728 - 739.

PMID- 28511267
TI  - Thermal Ablation of Lung Tumors: Focus on Microwave Ablation.
AB  - Background Image-guided thermal ablation can be used for the treatment of
      medically inoperable primary and metastatic lung cancer. These techniques are
      based on the heating up or freezing (cryoablation) of a volume of tissue around a
      percutaneous applicator that induces necrosis of the tumor. Method The English
      language literature concerning thermal ablation of the lung was reviewed.
      Radiofrequency ablation (RFA) is the most widely performed and investigated of
      these techniques. Microwave ablation (MWA) represents a relatively new
      alternative that shares the same indications and is conducted in a very similar
      fashion as RFA. It has been experimentally and clinically shown that MWA produces
      larger, more spherical ablation zones over shorter periods of time compared to
      RFA. Seven different MWA systems are available in Europe and the USA with
      significant differences in the size and shape of the produced ablation zones.
      Results The types of complications caused by MWA and their rates of occurrence
      are very similar to those caused by RFA. The local progression rates after MWA of
      lung malignancies vary between 0 % and 34 % and are similar to those in the RFA
      literature. Conclusion Despite technical improvements, the current generation of
      MWA systems has comparable clinical outcomes to those of RFA. Key Points  . MWA
      is a safe technique that should be considered one of the treatment options for
      medically inoperable lung tumors. . As thermal ablations of lung tumors are
      becoming more frequent, radiologists should be acquainted with the post-ablation
      imaging characteristics. . Although MWA has some theoretical advantages over RFA,
      the clinical outcomes are similar. Citation Format . Vogl TJ, Nour-Eldin NA,
      Albrecht MH et al. Thermal Ablation of Lung Tumors: Focus on Microwave Ablation.
      Fortschr Rontgenstr 2017; 189: 828 - 843.

PMID- 28511268
TI  - ?

PMID- 28511269
TI  - The role of birds in arboviral disease surveillance in Harris County and the City
      of Houston, Texas.
AB  - Avian arboviral surveillance is an integral part of any disease-based integrated
      mosquito control program. The Harris County Public Health Mosquito and Vector
      Control Division has performed arboviral surveillance in the wild birds of Harris
      County and the City of Houston since 1965. Blood samples from live trapped birds
      were tested for arboviral antibodies to West Nile virus (WNV), St. Louis
      encephalitis, Eastern equine encephalitis, and Western equine encephalitis. A
      dead bird surveillance program was created in 2002 with the arrival of WNV in
      Harris County. Since implementation, the program has detected considerable
      variability in viral activity with annual WNV seroprevelance rates ranging from
      2.9% to 17.7%, while the percentage of positive dead birds has ranged from 0.3%
      to 57.2%. In 2015, 1,345 live birds were sampled and 253 dead birds were tested,
      with WNV incidence rates of 16.5% and 5.9%, respectively.

PMID- 28511270
TI  - Laboratory and semi-field evaluations of two (transfluthrin) spatial repellent
      devices against Aedes aegypti (L.) (Diptera: Culicidae).
AB  - Two transfluthrin-based spatial repellent products (Raid Dual Action Insect
      Repellent and Home Freshener and Raid Shield (currently not commercially
      available), SC Johnson, Racine WI) were evaluated for spatial repellent effects
      against female Aedes aegypti (L.) mosquitoes under laboratory (wind tunnel) and
      semi-field (outdoor enclosure) conditions. The placement of either product in the
      wind tunnel significantly reduced host-seeking behaviors. The mean baseline
      (control) landing counts for the Raid Dual Action and Raid Shield were reduced by
      95% and 74% respectively. Mean probing counts for the Raid Dual Action were
      reduced by 95%, while the probing counts for the Raid Shield were decreased by
      69%. Baseline blood-feeding success was significantly reduced for both
      treatments: Raid Dual Action (100%) and Raid Shield (96%). Semi-field evaluations
      were conducted in outdoor enclosures at the Navy Entomology Center of Excellence,
      Jacksonville, Florida. A moderate reduction in mosquito entry into military style
      tents resulted when either product was placed near the tent opening. The Raid
      Shield reduced mosquito entry into tents by 88%, while the Dual Action decreased
      entry by 66%.

PMID- 28511271
TI  - Georgia's collaborative approach to expanding mosquito surveillance in response
      to Zika virus: a case study.
AB  - : Zika virus (ZIKV) was declared an international public health emergency by the
      World Health Organization on February 1, 2016. Due to the known and estimated
      range of the ZIKV mosquito vectors, southern and central US states faced
      increased risk of ZIKV transmission. With the state of Georgia hosting the
      world's busiest international airport, a climate that supports the ZIKV vectors,
      and limited surveillance (13 counties) and response capacity, the Department of
      Public Health (DPH) was challenged to respond and prevent ZIKV transmission. This
      case study describes and evaluates the state's surveillance capacity before and
      after the declaration of ZIKV as a public health emergency. METHOD: We analyzed
      surveillance data from the DPH to compare the geographical distribution of
      counties conducting surveillance, total number, and overall percentage of
      mosquito species trapped in 2015 to 2016. Counties conducting surveillance before
      and after the identification of the ZIKV risk were mapped using ArcMap 10.4.1.
      Using SAS (version 9.2) (SAS Institute, Inc, Cary, NC), we performed the
      independent 2 sample t test to test for differences in prevalence in both years,
      and a chi2 analysis to test for differences between numbers of species across the
      13 counties. In addition, weighted frequency counts of mosquitoes were used to
      test (chi2) an association between major mosquito vector species and 7 urban
      counties. Lastly, using data from 2012-2016, a time-trend analysis was conducted
      to evaluate temporal trends in species prevalence. RESULTS: From 2015 to 2016,
      surveillance increased from 13 to 57 (338% increase) counties geographically
      dispersed across Georgia. A total of 76,052 mosquitoes were trapped and
      identified in 2015 compared to 144,731 (90.3% increase) in 2016. Significant
      differences between species (P<.001) and significant associations (P<.0001)
      between 7 urban counties and major mosquito vectors were found. Significant
      differences in prevalence were found between several species and year
      highlighting species-year temporal trends. CONCLUSIONS: The DPH collaborative
      response to ZIKV allowed a rapid increase in its surveillance footprint. Existing
      and new partnerships were developed with the military and local health
      departments to expand and share data. This additional surveillance data allowed
      DPH to make sound public health decisions regarding mosquito-borne disease risks
      and close gaps in data related to vector distribution.

PMID- 28511272
TI  - A location-specific spreadsheet for estimating Zika risk and timing for Zika
      vector surveillance, using US military facilities as an example.
AB  - Local Zika virus transmission in the United States involving one or both of the
      known vector species, Aedes aegypti and Ae. albopictus, is of major concern. To
      assist efforts to anticipate the risks of transmission, we developed an Excel
      spreadsheet tool that uses vector and virus temperature thresholds, remotely
      sensed maximum temperature, and habitat suitability models to answer the
      questions: "is Zika transmission likely here?" and "when should we conduct vector
      surveillance?" An example spreadsheet, updated regularly and freely available,
      uses near real-time and forecast temperature data to generate guidance, based on
      a novel four level Zika risk code, for 733 US military facilities in the 50
      states, the District of Columbia, and the territories of Guam and Puerto Rico.

PMID- 28511273
TI  - Biosurveillance and morphological variations of larvae and pupae of common
      malaria vectors, Anopheles (Anopheles) Hyrcanus group species in the Republic of
      Korea.
AB  - A total of 4,576 Anopheles (Anopheles) Hyrcanus Group larvae belonging to 6
      species (An. belenrae, An. kleini, An. sinensis, An. pullus, An. lesteri, and An.
      sineroides) were collected from 7 different habitat types in 3 provinces of the
      Republic of Korea. The occurrence and relative abundance of 6 Anopheles species
      were noted. The descriptions in the article of the waxy body ornamentations or
      patterns of An. (Ano.) Hyrcanus Group larvae and pupae may be useful for rapid
      field species identification when conducting larval mosquito surveillance.

PMID- 28511274
TI  - A case of Chagas cardiomyopathy following infection in south central Texas.
AB  - Between 5 and 8 million people globally are infected with Trypanosoma cruzi, the
      causative parasitic agent of Chagas disease. The vast majority of incident
      infections originate in pockets of Latin America where domestic vector-borne
      transmission cycles are more common. Since 1955, when the first locally-acquired
      case was reported, fewer than 30 autochthonous cases have been documented in the
      United States. We describe the case of an 18-year-old US Air Force trainee, a
      native Texan with no travel history beyond the continental United States, who
      screened positive for T cruzi infection on blood donation and was subsequently
      found to have chronic Chagasic cardiomyopathy. This is the first documented case
      of Chagas disease in a US military trainee and one of the first known
      autochthonous cases of Chagasic cardiomyopathy in a Texas resident. Diagnostic,
      therapeutic, and military implications are discussed.

PMID- 28511275
TI  - Direct detection of Leishmania from clinical samples.
AB  - The ability to rapidly and accurately diagnose leishmaniasis is a military
      priority. Testing was conducted to evaluate diagnostic sensitivity and
      specificity of field-expedient Leishmania genus and visceral Leishmania specific
      dual-fluorogenic, hydrolysis probe (TaqMan), polymerase chain reaction assays
      previously established for use in vector surveillance. Blood samples of patients
      with confirmed visceral leishmaniasis and controls without the disease from
      Baringo District, Kenya, were tested. Leishmania genus assay sensitivity was 100%
      (14/14) and specificity was 84% (16/19). Visceral Leishmania assay sensitivity
      was 93% (13/14) and specificity 80% (4/5). Cutaneous leishmaniasis (CL) skin
      scrapes of patients from Honduras were also evaluated. Leishmania genus assay
      sensitivity was 100% (10/10). Visceral Leishmania assay specificity was 100%
      (10/10) from cutaneous leishmaniasis samples; no fluorescence above background
      was reported. These results show promise in a rapid, sensitive, and specific
      method for Leishmania direct detection from clinical samples.

PMID- 28511276
TI  - New records, distribution, and updated checklists of old world Phlebotomine sand
      flies, with emphasis on Africa, southwest Asia, and central Asia.
AB  - This article includes new records, distribution, and updated checklist of
      Phlebotomine sand flies (Psychodidae, Diptera) in the Old World (Africa including
      West Indian Ocean Islands, Southwest Asia, and Central Asia) based on specimen
      collections housed in different repositories worldwide. About 124 species have
      primary types housed in 5 repositories including holotypes (45 species, 4
      subspecies), syntypes (28 species, 3 subspecies), "types" (14 species), allotypes
      (10 species), paratypes (36 species, 3 subspecies), lectotypes (13 species), and
      cotype (5 species), mounted on 671 slides. New abbreviations were proposed for 2
      subgenera in the genus Phlebotomus and 6 subgenera in the genus Sergentomyia. New
      country records were noted in Phlebotomus (4 species in 4 subgenera in 7
      countries) and Sergentomyia (10 species in 4 subgenera in 8 countries). For
      species diversity in the Old World, Phlebotomus includes 92 species and 7
      subspecies in 9 subgenera, while Sergentomyia includes 166 species and 16
      subspecies in 12 subgenera. A total of 95 species and 7 subspecies of 2 genera
      (Phlebotomus and Sergentomyia) were recorded in Africa while about 26 species and
      16 subspecies in Southwest Asia and Central Asia.

PMID- 28511277
TI  - Operational mosquito and vector-borne diseases surveillance at Incirlik Air Base,
      Turkey.
AB  - Arboviruses on Incirlik Air Base, Turkey, pose a threat to military personnel and
      civilians, but might also be relevant for understanding the threats in
      neighboring conflict zones such as Syria. We reviewed 6 years of mosquito and
      arbovirus surveillance at Incirlik Air Base. Over 6,000 mosquitoes were
      identified as Aedes caspius, Anopheles claviger, Culex mimeticus, Cx. perexiguus,
      Cx. pipiens, Cx. sinaiticus, and Culiseta longiareolata. Almost all of the
      mosquitoes (more than 90%) were Cx. perexiguus or Cx. pipiens. Both West Nile
      virus and Sindbis virus were detected in 6 mosquito pools among collections made
      in 2013, 2014, and 2015.

PMID- 28511278
TI  - Vector-borne diseases of public health importance for personnel on military
      installations in the United States.

PMID- 28511279
TI  - Blast-associated traumatic brain injury in the military as a potential trigger
      for dementia and chronic traumatic encephalopathy.
AB  - Traumatic brain injuries (TBIs) resulting from blast exposures have significantly
      affected US military personnel throughout the world, particularly in Iraq and
      Afghanistan. From 2000-2016, more than 350,000 military service members were
      diagnosed with a TBI. Since the majority of blast-related TBIs are classified as
      mild with no definitive findings on physical examination or diagnostic studies,
      it is difficult to accurately diagnose individuals inflicted with such injuries.
      There are likely far more mild TBIs that remain undiagnosed in the military.
      Traumatic brain injury is a serious public health concern since it can lead to
      long-term neuropsychiatric changes such as posttraumatic stress disorder and
      various forms of dementia. Blast-related TBI has also been linked with
      neuropsychiatric dysfunction that is commonly seen in athletes that have suffered
      chronic traumatic encephalopathy. Further research is needed to aid in
      prevention, diagnostic studies, and care of military service members and veterans
      who have suffered a TBI.

PMID- 28511280
TI  - Challenges of practicing environmental epidemiology in the US military.

PMID- 28511281
TI  - Indirect military occupational lead exposure to children at home: a case report.

PMID- 28511282
TI  - Livedoid Vasculopathy.

PMID- 28511283
TI  - A different inhibitor is required for overcoming entecavir resistance: a
      comparison of four rescue therapies in a retrospective study.
AB  - AIMS: Little clinical data are available regarding re-establishing the effective
      inhibition of entecavir (ETV)-resistant mutants. In this retrospective study, we
      aimed to compare the efficacies of four treatment regimens as rescue therapy for
      those chronic hepatitis B (CHB) patients with ETV resistance. METHODS: A total of
      65 patients with ETV resistance were assigned either with tenofovir disoproxil
      fumarate (TDF) monotherapy (n = 21), ETV (0.5 mg) plus adefovir (ADV) combination
      therapy (n = 19), ETV (1.0 mg) monotherapy (n = 11) or ETV (0.5 mg) plus TDF
      combination therapy (n = 14). The efficacy and safety of four treatment regimens
      were compared. RESULTS: There were no significant differences among the four
      study groups in baseline characteristics, including HBV DNA levels (chi2  =
      0.749, P = 0.862) and hepatitis B e antigen-positivity (chi2  = 0.099, P =
      0.992). The median reduction in serum HBV DNA level from baseline at week 48 was 
      2.37 +/- 1.07 log10 IU ml-1 , -2.16 +/- 0.81 log10 IU ml-1 , -1.17 +/- 1.23 log10
      IU ml-1 and -2.49 +/- 1.10 log10 IU ml-1 , respectively (F = 4.078, P = 0.011).
      The TDF group and ETV (0.5 mg) + TDF group have the highest undetectable HBV DNA
      rate (76.19% vs. 78.57%) compared to the ETV (0.5 mg) + ADV group and the ETV
      (1.0 mg) group (63.16% vs. 18.18%, respectively). Two patients in the ETV (1.0
      mg) group experienced virological breakthrough at week 48 and was attributed to
      poor drug adherence. CONCLUSIONS: TDF monotherapy appeared to deliver the highest
      undetectable HBV DNA rate in patients with ETV resistance, and ADV plus ETV
      combination therapy could be another choice for patients with financial
      restraint.

PMID- 28511284
TI  - Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a
      cross-sectional study of the 26 EU-labelled fragrance allergens.
AB  - BACKGROUND: For cosmetics, it is mandatory to label 26 fragrance substances,
      including all constituents of fragrance mix I (FM I) and fragrance mix II (FM
      II). Earlier reports have not included oxidized R-limonene [hydroperoxides of R
      limonene (Lim-OOH)] and oxidized linalool [hydroperoxides of linalool (Lin-OOH)],
      and breakdown testing of FM I and FM II has mainly been performed in selected,
      mix-positive patients. OBJECTIVES: To report the prevalence of sensitization to
      the 26 fragrances, and to assess concomitant reactivity to FM I and/or FM II.
      METHODS: A cross-sectional study on consecutive dermatitis patients patch tested
      with the 26 fragrances and the European baseline series from 2010 to 2015 at a
      single university clinic was performed. RESULTS: Of 6004 patients, 940 (15.7%,
      95%CI: 14.7-16.6%) were fragrance-sensitized. Regarding the single fragrances,
      most patients were sensitized to Lin-OOH (3.9%), Evernia furfuracea (3.0%), Lim
      OOH (2.5%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.1%).
      Significantly fewer patients were 'FM I-positive and constituent-positive' than
      'FM II-positive and constituent-positive' (32.7% versus 57.0%, p < 0.0001).
      Additionally, significantly more patients were 'FM II-negative but constituent
      positive' than 'FM I-negative but constituent-positive' (12.4% versus 3.2%, p =
      0.0008). CONCLUSIONS: Non-mix fragrances are the most important single fragrance
      allergens among consecutive patients. The test concentration of the single FM I
      constituents should be increased when possible.

PMID- 28511285
TI  - Association of Increased F4/80high Macrophages With Suppression of Serum-Transfer
      Arthritis in Mice With Reduced FLIP in Myeloid Cells.
AB  - OBJECTIVE: Macrophages are critical in the pathogenesis of rheumatoid arthritis
      (RA). We recently demonstrated that FLIP is necessary for the differentiation
      and/or survival of macrophages. We also showed that FLIP is highly expressed in
      RA synovial macrophages. This study was undertaken to determine if a reduction in
      FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates
      serum-transfer arthritis. METHODS: Mice with Flip deleted in myeloid cells
      (Flipf/f LysMc/+ mice) and littermate controls were used. Arthritis was induced
      by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by
      clinical score and change in ankle thickness, and joints were examined by
      histology and immunohistochemistry. Cells were isolated from the ankles and bone
      marrow of the mice and examined by flow cytometry, real-time quantitative reverse
      transcriptase-polymerase chain reaction, or Western blotting. RESULTS: In
      contrast to expectations, Flipf/f LysMc/+ mice developed more severe arthritis
      early in the clinical course, but peak arthritis was attenuated and the
      resolution phase more complete than in control mice. Prior to the induction of
      serum-transfer arthritis, the number of tissue-resident macrophages was reduced.
      On day 9 after arthritis induction, the number of F4/80high macrophages in the
      joints of the Flipf/f LysMc/+ mice was not decreased, but increased. FLIP was
      reduced in the F4/80high macrophages in the ankles of the Flipf/f LysMc/+ mice,
      while F4/80high macrophages expressed an antiinflammatory phenotype in both the
      Flipf/f LysMc/+ and control mice. CONCLUSION: Our observations suggest that
      reducing FLIP in macrophages by increasing the number of antiinflammatory
      macrophages may be an effective therapeutic approach to suppress inflammation,
      depending on the disease stage.

PMID- 28511287
TI  - Generation and characterization of highly purified canine Schwann cells from
      spinal nerve dorsal roots as potential new candidates for transplantation
      strategies.
AB  - Schwann cells are promising candidates for transplantation strategies in the
      central nervous system by promoting axonal regeneration. The dog represents a
      translational model for human spinal cord injury (SCI) for studies with new
      repair strategies after intervertebral disk herniation (IVDH). To overcome the
      necessity for an additional surgical procedure, for the first time a protocol for
      the isolation and purification of canine Schwann cells from spinal nerve biopsies
      during standard hemilaminectomy in IVDH-affected paraplegic dogs for potential
      transplantation has been developed. Purity was assessed by flow cytometry. The
      results were compared with biopsies from dogs without SCI. Within 26 +/- 4 days,
      90.2 +/- 8.8% p75 neurotrophin receptor (p75NTR )-positive cells were achieved in
      IVDH dogs. The total cell count in acute/subacute and chronic IVDH
      (acute/subacute: 6.82 +/- 6.36 * 106 ; chronic: 2.29 +/- 2.00 * 106 ) differed
      significantly (p = 0.0120) at the potential time point of transplantation. No
      differences in culture period and purity were detected between dogs with and
      without IVDH. Despite the small sample size and the altered environment, the
      isolation of Schwann cells was successful. Negative influences on isolation and
      purification due to potential pathological changes at the biopsy site of IVDH
      diseased dogs were ruled out by comparison of Schwann cell pellets from diseased
      and control dogs. Finally, the functionality of Schwann cells from dogs with IVDH
      was outlined in co-culture experiments with canine dorsal root ganglion neurons.
      In conclusion, nerve root biopsies provide a sufficient number of highly purified
      and functional Schwann cells within a useful time period for novel therapeutic
      strategies in dogs with SCI.

PMID- 28511288
TI  - Tele-Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid
      Arthritis: Results of a Randomized Controlled Trial.
AB  - OBJECTIVE: To test the effect of patient-reported outcome (PRO)-based tele-health
      followup for tight control of disease activity in patients with rheumatoid
      arthritis (RA), and the differences between tele-health followup performed by
      rheumatologists or rheumatology nurses. METHODS: A total of 294 patients were
      randomized (1:1:1) to either PRO-based tele-health followup carried out by a
      nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup
      by physicians. The primary outcome was a change in the Disease Activity Score in
      28 joints (DAS28) after week 52. Secondary outcomes were physical function,
      quality of life, and self-efficacy. The noninferiority margin was a DAS28 score
      change of 0.6. Mean differences were estimated following per protocol, intent-to
      treat (ITT), and multivariate imputation analysis. RESULTS: Overall, patients had
      low disease activity at baseline and end followup. Demographics and baseline
      characteristics were similar between groups. Noninferiority was established for
      the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO
      TR versus control were -0.10 (90% confidence interval [90% CI] -0.30, 0.13) and 
      0.19 (90% CI -0.41, 0.02) between PRO-TN versus control. When including 1 yearly
      visit to the outpatient clinic, patients in PRO-TN had mean +/- SD 1.72 +/- 1.03
      visits/year, PRO-TR had 1.75 +/- 1.03 visits/year, and controls had 4.15 +/- 1.0
      visits/year. This included extra visits due to inflammatory flare. CONCLUSION:
      Among RA patients with low disease activity or remission, a PRO-based tele-health
      followup for tight control of disease activity in RA can achieve similar disease
      control as conventional outpatient followup. The degree of disease control did
      not differ between patients seen by rheumatologists or rheumatology nurses.

PMID- 28511286
TI  - Who achieves low risk drinking during alcohol treatment? An analysis of patients
      in three alcohol clinical trials.
AB  - BACKGROUND AND AIMS: There is evidence that low-risk drinking is possible during
      the course of alcohol treatment and can be maintained following treatment. Our
      aim was to identify characteristics associated with low-risk drinking during
      treatment in a large sample of individuals as they received treatment for alcohol
      dependence. DESIGN: Integrated analysis of data from the Combined
      Pharmacotherapies and Behavioral Intervention (COMBINE) study, Project MATCH
      (Matching Alcoholism Treatments to Client Heterogeneity) and the United Kingdom
      Alcohol Treatment Trial (UKATT) using repeated-measures latent class analysis to
      identify patterns of drinking and predictors of low-risk drinking patterns during
      treatment. SETTING: United States and United Kingdom. PARTICIPANTS: Patients (n =
      3589) with alcohol dependence receiving treatment in an alcohol clinical trial
      were primarily male (73.0%), white (82.0%) and non-married (41.7%), with an
      average age of 42.0 (standard deviation = 10.7). MEASUREMENTS: Self-reported
      weekly alcohol consumption during treatment was assessed using the Form-90 and
      validated with biological verification or collateral informants. FINDINGS: Seven
      patterns of drinking during treatment were identified: persistent heavy drinking
      (18.7% of the sample), increasing heavy drinking (9.6%), heavy and low-risk
      drinking (6.7%), heavy drinking alternating with abstinence (7.9%), low-risk
      drinking (6.8%), increasing low-risk drinking (10.5%) and abstinence (39.8%).
      Lower alcohol dependence severity and fewer drinks per day at baseline
      significantly predicted low-risk drinking patterns [e.g. each additional drink
      prior to baseline predicted a 27% increase in the odds of expected classification
      in heavy drinking versus low-risk drinking patterns; odds ratio = 1.27 (95%
      confidence interval (CI) = 1.10, 1.47, P = 0.002]. Greater negative mood and more
      heavy drinkers in the social network were significant predictors of expected
      membership in heavier drinking patterns. CONCLUSIONS: Low-risk drinking is
      achievable for some individuals as they undergo treatment for alcohol dependence.
      Individuals with lower dependence severity, less baseline drinking, fewer
      negative mood symptoms and fewer heavy drinkers in their social networks have a
      higher probability of achieving low-risk drinking during treatment.

PMID- 28511289
TI  - Brief Report: Group 3 Innate Lymphoid Cells in Human Enthesis.
AB  - OBJECTIVE: Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier
      tissues such as the gut and the skin, two important sites of disease in
      spondyloarthritis (SpA). This study was undertaken to investigate whether normal
      or injured human enthesis, a key target tissue in early SpA, harbors ILC3s in
      entheseal soft tissue and adjacent perientheseal bone. METHODS: Interspinous
      ligament and spinous process bone from donors with no systemic inflammatory
      disease were collected, enzymatically digested, and immunophenotyped. The
      immunologic profile of entheseal cells was examined, and the transcriptional
      profile of sorted ILC3s was compared to that of ILC3s isolated from SpA synovial
      fluid (SF). To assess the ability of entheseal tissue to produce interleukin-17
      (IL-17) and IL-22, entheseal digests were stimulated with IL-23 and IL-1beta.
      Osteoarthritic and ruptured Achilles tendon tissue was examined histologically.
      RESULTS: The proportion of ILCs in human entheseal soft tissue was higher than
      that in peripheral blood (P = 0.008); entheseal soft tissue and perientheseal
      bone both had a higher proportion of NKp44+ ILC3s (P = 0.001 and P = 0.043,
      respectively). Studies of retinoic acid receptor-related orphan nuclear receptor
      gammat (RORgammat), STAT3, and IL-23 receptor transcript expression validated the
      entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s
      isolated from enthesis and from SpA SF. Stimulation of normal entheseal digests
      with IL-23/IL-1beta led to up-regulation of IL-17A transcript, and histologic
      examination of injured/damaged entheses revealed the presence of RORgammat
      expressing cells. CONCLUSION: This work shows that human enthesis harbors a
      resident population of ILC3s, with the potential to participate in the
      pathogenesis of SpA.

PMID- 28511290
TI  - First use of antidepressant medication in male partners of women with breast
      cancer in Denmark from 1998 to 2011.
AB  - OBJECTIVE: A diagnosis of breast cancer disrupts the life of the patient, but
      also the partner may experience adverse psychological effects. We examined
      partners' risk for first use of antidepressant medication, as a proxy for
      pharmacologically treated depression. METHODS: By linkage of national registers,
      we identified 1 420 592 depression-free men living with a cancer-free female
      partner in 1998 to 2011. During follow-up, breast cancer was diagnosed in female
      partners of 26 256 men. In Poisson regression models, we estimated the rate
      ratios for first use of antidepressant medication compared to partners of breast
      cancer-free women. Cox regression analyses examined associations between exposed
      partners' sociodemographic characteristics, somatic comorbidity, death of female
      partner, and first use of antidepressant medication. RESULTS: Male partners of
      women with breast cancer had an increased rate ratio of 1.08 (95% CI, 1.03-1.13)
      for first use of antidepressant medication compared to the background population,
      corresponding to excess absolute risk of 12 cases per 10 000 person-years. This
      increased risk persisted throughout 14 years of follow-up. Higher age, shorter
      education, somatic comorbidity, and death of female partner were associated with
      increased risk among men whose partner had breast cancer. CONCLUSION: The modest,
      but long term, increased risk for first use of antidepressant medication calls
      for attention by health care professionals to symptoms of depression among
      partners of breast cancer patients.

PMID- 28511292
TI  - Role of Gut Inflammation in Altering the Monocyte Compartment and Its
      Osteoclastogenic Potential in HLA-B27-Transgenic Rats.
AB  - OBJECTIVE: To investigate the relationship between intestinal inflammation and
      the central and peripheral innate immune system in the pathogenesis of HLA-B27
      associated spondyloarthritis using an HLA-B27-transgenic (B27-Tg) rat model.
      METHODS: The myeloid compartment of the blood and bone marrow (BM) of B27-Tg
      rats, as well as HLA-B7-Tg and non-Tg rats as controls, was evaluated by flow
      cytometry. Plasma from rats was assessed by enzyme-linked immunosorbent assay for
      levels of CCL2 and interleukin-1alpha (IL-1alpha). Rats were treated with
      antibiotics for 4 weeks, and the myeloid compartment of the blood and BM was
      evaluated by flow cytometry. The osteoclastogenic potential of BM-derived cells
      from antibiotic-treated rats, in the presence or absence of tumor necrosis factor
      (TNF), was evaluated in vitro. RESULTS: B27-Tg rats had substantially higher
      numbers of circulating Lin-CD172a+CD43low monocytes as compared to control
      animals, and this was significantly correlated with higher levels of plasma CCL2.
      Antibiotic treatment of B27-Tg rats markedly reduced the severity of ileitis,
      plasma levels of CCL2 and IL-1alpha, and number of BM and blood Lin
      CD172a+CD43low monocytes, a cell subset shown in the present study to have the
      greatest in vitro osteoclastogenic potential. Antibiotic treatment also prevented
      the TNF-dependent enhancement of osteoclastogenesis in B27-Tg rats. CONCLUSION:
      Microbiota-dependent intestinal inflammation in B27-Tg rats directly drives the
      systemic inflammatory and bone-erosive potential of the monocyte compartment.

PMID- 28511293
TI  - Enterobacter aerogenes ZDY01 Attenuates Choline-Induced Trimethylamine N-Oxide
      Levels by Remodeling Gut Microbiota in Mice.
AB  - Trimethylamine N-oxide (TMAO), which is transformed from trimethylamine (TMA)
      through hepatic flavin-containing monooxygenases, can promote atherosclerosis.
      TMA is produced from dietary carnitine, phosphatidylcholine, and choline via the
      gut microbes. Previous works have shown that some small molecules, such as
      allicin, resveratrol, and 3,3-dimethyl-1-butanol, are used to reduce circulating
      TMAO levels. However, the use of bacteria as an effective therapy to reduce TMAO
      levels has not been reported. In the present study, 82 isolates were screened
      from healthy Chinese fecal samples on a basal salt medium supplemented with TMA
      as the sole carbon source. The isolates belonged to the family
      Enterobacteriaceae, particularly to genera Klebsiella, Escherichia, Cronobacter,
      and Enterobacter. Serum TMAO and cecal TMA levels were significantly decreased in
      choline-fed mice treated with Enterobacter aerogenes ZDY01 compared with those in
      choline-fed mice treated with phosphate-buffered saline. The proportions of
      Bacteroidales family S24-7 were significantly increased, whereas the proportions
      of Helicobacteraceae and Prevotellaceae were significantly decreased through the
      administration of E. aerogenes ZDY01. Results indicated that the use of
      probiotics to act directly on the TMA in the gut might be an alternative approach
      to reduce serum TMAO levels and to prevent the development of atherosclerosis and
      "fish odor syndrome" through the effect of TMA on the gut microbiota.

PMID- 28511294
TI  - Genome Sequences of Spinach Deltapartitivirus 1, Spinach Amalgavirus 1, and
      Spinach Latent Virus Identified in Spinach Transcriptome.
AB  - Complete genome sequences of three new plant RNA viruses, Spinach
      deltapartitivirus 1 (SpDPV1), Spinach amalgavirus 1 (SpAV1), and Spinach latent
      virus (SpLV), were identified from a spinach (Spinacia oleracea) transcriptome
      dataset. The RNA-dependent RNA polymerases (RdRps) of SpDPV1, SpAV1, and SpLV
      showed 72%, 53%, and 93% amino acid sequence identities with the homologous RdRp
      of the most closely related virus, respectively, suggesting that SpDPV1 and SpAV1
      were novel viruses. Sequence similarity and phylogenetic analyses revealed that
      SpDPV1 belonged to the genus Deltapartitivirus of the family Partitiviridae,
      SpAV1 to the genus Amalgavirus of the family Amalgaviridae, and SpLV to the genus
      Ilarvirus of the family Bromoviridae. Based on the demarcation criteria, SpDPV1
      and SpAV1 are considered as novel species of the genera Deltapartitivirus and
      Amalgavirus, respectively. This is the first report of these two viruses from
      spinach.

PMID- 28511291
TI  - Effect of Fatigue, Older Age, Higher Body Mass Index, and Female Sex on
      Disability in Early Rheumatoid Arthritis in the Treatment-to-Target Era.
AB  - OBJECTIVE: To compare disease activity and disability over 2 years in early
      rheumatoid arthritis (RA) before and after implementation of treat-to-target
      therapy and identify predictors of adverse outcome. METHODS: The Yorkshire Early
      Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and
      2009, treated with a step-up approach. The Inflammatory Arthritis Continuum study
      (IACON) recruited cases between 2010 and 2014 and treated to target. A total of
      384 IACON cases met 2010 American College of Rheumatology/European League Against
      Rheumatism criteria. Latent growth curves of change in Disease Activity Score in
      28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared
      between YEAR and IACON. Latent class growth analysis identified trajectories of
      change. Baseline predictors of trajectories were identified using logistic
      regression. RESULTS: The mean DAS28 over 2 years was lower in IACON than in YEAR.
      Latent trajectories of HAQ change in YEAR were high stable (21% of cohort),
      moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and
      low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue
      predicted adverse HAQ trajectories (high stable and moderate reducing). Odds
      ratios (ORs) for moderate reducing compared to low reducing for women were 2.58
      (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44,
      14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI
      1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON. CONCLUSION: Treat-to
      target therapy gave more favorable trajectories of change in DAS28 and HAQ, but
      adverse HAQ trajectory was more likely in women with greater fatigue, suggesting
      such patients would benefit from interventions to improve function as well as
      reduce inflammation.

PMID- 28511295
TI  - Anaerobic Ammonium-Oxidizing Bacteria in Cow Manure Composting.
AB  - Composting is widely used to transform waste into valuable agricultural organic
      fertilizer. Anaerobic ammonium-oxidizing (anammox) bacteria play an important
      role in the global nitrogen cycle, but their role in composting remains poorly
      understood. In the present study, the community structure, diversity, and
      abundance of anammox bacteria were analyzed using cloning and sequencing methods
      by targeting the 16S rRNA gene and the hydrazine oxidase gene (hzo) in samples
      isolated from compost produced from cow manure and rice straw. A total of 25
      operational taxonomic units were classified based on 16S rRNA gene clone
      libraries, and 14 operational taxonomic units were classified based on hzo gene
      clone libraries. The phylogenetic tree analysis of the 16S rRNA gene and deduced
      HZO protein sequences from the corresponding encoding genes indicated that the
      majority of the obtained clones were related to the known anammox bacteria
      Candidatus "Brocadia," Candidatus "Kuenenia," and Candidatus "Scalindua." The
      abundances of anammox bacteria were determined by quantitative PCR, and between
      2.13 * 105 and 1.15 * 106 16S rRNA gene copies per gram of compost were found.
      This study provides the first demonstration of the existence of anammox bacteria
      with limited diversity in cow manure composting.

PMID- 28511296
TI  - (E)-2-Methoxy-4-(3-(4-Methoxyphenyl)Prop-1-en-1-yl)Phenol Induces Apoptosis in
      HeLa Cervical Cancer Cells via the Extrinsic Apoptotic Pathway.
AB  - (E)-2-Methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP), derived from
      butenal, is a recently synthesized Maillard reaction product. Owing to its
      novelty, little is known about the function of MMPP. In this study, we elucidated
      the effects of MMPP on apoptosis in cervical cancer by using the HeLa cervical
      cancer cell line, which is widely used in cancer research. We observed that MMPP
      was cytotoxic to HeLa cells and induced activation of caspase-3, -8, and -9,
      without affecting the expression of the viral oncogenes E6 and E7. In particular,
      the expression of the death receptors DR5 and FAS was significantly increased by
      MMPP treatment. There were no significant alterations of mitochondrial intrinsic
      factors. Taking all these results together, our findings show that MMPP primarily
      induces apoptosis in HeLa cervical cancer cells via the extrinsic apoptotic
      signaling pathway, accompanied by an enhanced expression of death receptors.

PMID- 28511297
TI  - [The effect of complement C3a receptor antagonist in the kidney immune injury in
      trichloroethylene-sensitized mice].
AB  - Objective: To explore the effect of complement C3 a-C3a receptor in the kidney
      immune inju-ry in trichloroethylene-sensitized mice by using C3a receptor
      specific antagonist C3aRA and discuss the patho-genesis of kidney injury in
      occupational dermatitis medicamentosa-like of trichloroethylene (ODMLT) .
      Methods: 42 female 6~8 weeks old BALB/c mice of specific pathogen free were
      randomly divided into blank control group (5) , solvent control group (5) , TCE
      treatment group (16) and TCE+C3aRA treatment group (16) . The TCE treat-ment
      group and TCE+C3aRA treatment group were further divided into the sensitized
      group and the non-sensi-tized group according to the skin sensitization test
      score. Renal function was detected by biochemical detection kit; expression of
      C3aR in kidney tissue was detected by qPCR; expression of IL-1beta and TNF-alpha
      protein were de-tected by immunohistochemical. Results: Compared with solvent
      control group and corresponding non-sensitized group, CRE and BUN in TCE
      sensitized group and TCE + C3aRA sensitized group were significantly increased
      (P<0.05) . Compared with TCE sensitized group, CRE and BUN in TCE+C3aRA
      sensitized group were signifi-cantly decreased (P<0.05) . Compared with solvent
      control group and TCE non-sensitized group, the expression level of C3aR gene in
      kidney tissue in TCE sensitized group was significantly increased (P<0.05) .
      There was a large number of IL-1beta and TNF-alpha protein expression in kidney
      tissue in TCE sensitized group and TCE+C3aRA sensitized group. Compared with the
      TCE sensitized group, the expression level of IL-1beta and TNF-alpha protein in
      kidney tissue in TCE+C3aRA sensitized group was significantly decreased (P<0.05)
      . Conclusion: C3a-C3aR may be involved in the kidney immune injury in TCE
      sensitized mice, C3aRA has a protective effect on the kid-ney immune injury in
      TCE sensitized mice.

PMID- 28511298
TI  - [Influence of aluminum chloride exposure on embryonic development of zebrafish
      and neurobehavior of juvenile fish].
AB  - Objective: To investigate the influence of aluminum chloride (AlCl(3)) solution
      on the embryon-ic development of zebrafish and neurobehavior of juvenile fish.
      Methods: The embryos of zebrafishat 6 hours after fertilization were exposed to
      AlCl(3) solution at a concentration of 0, 55.0, 60.5, 66.6, 73.5, 80.5, or 100.0
      mg/L, and embryonic hatching rates at 48 and 72 hours after fertilization were
      calculated. The embryos of zebrafishat 6 hours after fertilization were exposed
      to AlCl(3) solution at a concentration of 0, 60.0, 72.0, 86.4, 103.7, or 124.4
      mg/L, and the embryonic mortality rates at 12, 24, 48, 72, and 96 hours after
      fertilization were calculat-ed. The embryos of zebrafish at 6 hours after
      fertilization were exposed to AlCl(3) solution at a concentration of 0, 50, 100,
      200, 400, or 800 MUg/L, and the changes in the neurobehavior of juvenile fish
      were observed after hatching, including touch-escape reaction at 72 hours after
      fertilization and autonomic movement and panic es-cape reflex at 7 days after
      fertilization. Results: Compared with the 0 mg/L group, the>=66.6 mg/L group had
      a sig-nificant reduction in embryonic hatching rate at 48 and 72 hours after
      fertilization, and the >=72.0 mg/L group had a significant increase in embryonic
      mortality rate at 96 hours after fertilization (P<0.05) . Compared with the 0
      MUg/L group, the>=100 MUg/L group had a significant reduction in the number of
      times of touch-escape reaction (P<0.05) .Compared with the 0 and 50 MUg/L groups,
      the 100-800 MUg/L groups had significant reductions in total movement distance
      and average speed (P<0.05) . Compared with the dark period before illumination,
      all groups had a significant increase in movement speed during the light period
      of the panic escape reflex test (i.e., the third minute) (P<0.05) ; within 2
      minutes after the light was turned off, there was no significant change in
      movement speed in the 0-200 MUg/L groups (P>0.05) ; the 400 and 800 MUg/L groups
      had a significant increase in movement speed (P<0.05) . Conclusion: AlCl(3)
      exposure may cause embryonic developmental disorder in zebrafish and ab-normal
      neurobehavior in juvenile fish.

PMID- 28511299
TI  - [Value of DNA content in comet tail in predicting changes in blood cell counts in
      workers exposed to benzene].
AB  - Objective: To investigate the value of DNA content in comet tail (TailDNA) in
      predicting the changes in peripheral blood cell counts in workers exposed to
      benzene. Methods: In 2011, cluster sampling was used to select 150 male workers
      exposed to benzene in a petrochemical factory. Cubital venous blood and urine
      samples were collected for routine blood rest, comet assay, and measurement of s
      phenylmercapturic acid (SPMA) and urine creatinine. The population was divided
      into groups according to urinary SPMA or TailDNA, and routine blood test results
      within 3 years were collected to analyze the changes in blood cell counts.
      Results: The low-SPMA group had significantly higher white blood cell and
      neutrophilcounts in all years than the high-SPMA group (P<0.05) . The low-Tail
      DNA group had a significant increase in platelet count from 2012 to 2014 (P<0.05)
      , while the high-Tail DNA group had no significant change (P>0.05) . During the 4
      year period, the high-TailDNA group had a significantly lower red blood cell
      count than the low-TailDNA group (P<0.05) . The high-TailDNA group showed a
      gradual reduction in white blood cell count over time (beta=-0.113, P<0.05) , and
      the low-TailDNA group showed no trend of the reduction in white blood cell count
      (P>0.05) . Conclusion: TailDNA can be used to predict the changes in blood cell
      counts in workers exposed to benzene.

PMID- 28511300
TI  - [Mediator effect analysis of the trait coping style on job stress and fatigue of
      the military personnel stationed in plateau and high cold region].
AB  - Objective: To investigate the fatigue status of military personnel stationed in
      plateau and high cold region, and to analyze the mediator effect of trait coping
      style on job stress and fatigue. Methods: In October 2010, with the method of
      cluster random sampling survey, 531 military personnel stationed in plateau and
      high cold region were chosen as subject. The fatigue status were evaluated by the
      Chinese version multidimensional fatigue inventory (MFI-20) , job stress were
      evaluated by the Job Stress Survey (JSS) , and trait coping style were evaluated
      by the Trait Coping Style Questionnaire (TCSQ) . Results: According to the
      information of different population characteristics, mean rank of physical
      fatigue about the urban (town) group were higher than that of rural group (Z=
      2.200, P<0.05) ; mean rank of reduced motivation about the urban (town) group
      were higher than that of rural group (Z=-2.781, P<0.05) ; mean rank of general
      fatigue scores about the urban (town) group were higher than that of rural group
      (Z=-3.026, P<0.05) ; mean rank of physical fatigue about the up or equal 20-years
      old age group were higher than that of below 20-years old age group (Z=-4.045,
      P<0.05) ; mean rank of reduced motivation about the up or equal 20-years old age
      group were higher than that of below 20-years old age group (Z=-2.182, P<0.05) ;
      mean rank of mental fatigue about the up or equal 20-years old age group were
      higher than that of below 20-years old age group (Z=-2.879, P<0.05) ; mean rank
      of general fatigue scores about the up or equal 20-years old age group were
      higher than that of below 20-years old age group (Z=-3.647, P<0.05) ; mean rank
      of reduced motivation were significant statistical difference among the military
      officers, sergeancy and soldier group (F=18.965, P<0.05) ; mean rank of general
      fatigue scores were significant statistical difference among the military
      officers, sergeancy and soldier group (F=14.711, P<0.05) . The score of negative
      coping style were positively correlated with the score of physical fatigue
      (r(s)=0.129) , reduced activity (r(s)=0.123) , reduced motivation (r(s)=0.149)
      and general fatigue (r(s)=0.174) respectively, the score of organizational
      support lack strength were positively correlated with the score of physical
      fatigue (r(s)=0.090) , reduced activity (r(s)=0.098) , reduced motivation
      (r(s)=0.099) and general fatigue (r(s)=0.130) respectively. The mediator effect
      of negative coping style on the job stress and fatigue was 0.013 (P<0.01) .
      Conclusion: The fatigue statuses of the urban (town) group and the up or equal 20
      years old age group are poor, and the negative coping style plays mediator effect
      on the job stress and fatigue.

PMID- 28511301
TI  - [Mediating role of over-commitment in the relationship between effort, reward and
      burnout].
AB  - Objective: To explore the mediating role of over-commitment in the relationship
      between occupational stressors and job burnout, and to offer more
      specificevidence-based information in exploring the work related health effects
      of over-commitment. Methods: A total of 1994 samples from electronic
      manufacturing service industry were collected in Guangdong province based on self
      rated questionnaire after written consent from June to July, 2015. The Effort
      Reward Imbalance questionnaire and Maslach Burnout Invertory-General Survey were
      used for the measurement of occupational stress and job burnout. And hierarchical
      regression and Bootstrap test were conducted for data analysis. Results: High
      effort (0.28, 0.24-0.33) and low reward (-0.37, -0.42--0.33) were significantly
      associated with high over-commitment when gender, age and position had been
      controlled. Standardizedregression coefficient of effort to emotional exhaustion,
      depersonalization and personal accomplishment were 0.63 (95%CI: 0.54-0.71) ,0.18
      (95%CI: 0.10-0.26) ,0.32 (95%CI: 0.21-0.43) , P<0.05; and standardized regression
      coefficient of reward to emotional exhaustion, depersonalization and personal
      accomplishment were-0.60 (95%CI: -0.68--0.52) ,-0.93 (95%CI: -1.01--0.86) ,-0.46
      (95%CI: -0.35--0.58) , P<0.05. Bootstrap test indicated the mediation of over
      commitment were statistically significant, and mediating effect ranges from 0.093
      to 0.218 (P<0.05) . Conclusion: Over-commitment can mediate the relationship
      between occupational stressors (job effort and reward) and burnout, and the
      effect varies from different workingconditions.

PMID- 28511302
TI  - [Epidemiological and occupational characteristics of occupational chemical
      poisoning in Tianjin city during 2006-2015].
AB  - Objective: To provide scientific evidence for the prevention and control measures
      of acute and chronic occupational poisoning by analyzing the epidemiological and
      occupational characteristics of occupational chemical poisoning cases reported in
      Tianjin city during 2006-2015. Methods: In September 2016, based on the China
      Disease Control and Prevention Information System, a database of occupational
      poisoning cases in Tianjin from 2006 to 2015 was established. The epidemiological
      characteristics of occupational poisoning were analyzed including three
      distributions firstly, and then the occupational characteristics were analyzed
      such as length of service, industry distribution and source of poison. Results:
      There were 174 occupational poisoning patients in Tianjin from 2006 to 2015,
      including 16 cases of acute poisoning (9.20%) and 158 cases of chronic poisoning
      (90.8%) , and the proportion of occupational poisoning cases reported in Binhai
      New Area is the highest. The number of reported cases of chronic occupational
      poisoning shows a downward trend. Occupational poisoning cases are concentrated
      mainly in the age of 40-60 years and length of service of 10-20 years. The high
      incidence of occupational poisoning mainly exists in the chemical raw materials
      and chemical manufacturing industry and general, professional equipment
      manufacturing industry. Acute poisoning was mainly by asphyxial gas (50.00%) ,
      and chronic poisoning was mainly by organic solvent (43.67%) . Conclusion: The
      distribution of occupational poisoning cases in diverse toxic types and regions
      in Tianjin are quite different. The occupational safety precautions of the
      chemical raw materials and chemical products manufacturing and occupational
      poisoning control work in Binhai new area should be strengthened to reduce the
      occurrence of occupational poisoning.

PMID- 28511303
TI  - [Association of XRCC1 gene polymorphism and low dose ionizing radiation with
      peripheral blood lymphocyte micronucleus].
AB  - Objective: To explore the effects of X-ray repair cross complementing gene 1
      (XRCC1) polymorphism and low dose ionizing radiation exposure on radiology
      professionals' peripheral blood lymphocyte micronucleus. Methods: A matched case
      control study was designed. From 2013 to 2015, 1 102 radiology professionals with
      micronucleus test rusults, and 45 cases with present micronucleus were enroled
      into case group. 180 diagnostic radiology technicians detecting no micronucleus
      were chosen as control group, cases and controls were 1?4 mached on gender, age
      <=40 or >40 years old. According to the detection of micronucleus levels (00/00,
      10/00, 20/00) , the objects of our study were divided into the reference group,
      the low detection group and the medium detection group. The form of radiation
      workers' occupational health examination was used to collect the general baseline
      of the research objects, history of smoking, drinking, poisonous and harmful
      material exposure, past medical history, accumulated illuminated dose and
      lymphocyte micronucleus rates (0/00) , etc. Using restriction fragment length
      polymorphism polymerase chain reaction (RFLP-PCR) technology for genotyping;
      Compared the baseline data and radiation exposure level between the
      differentmicrokernel detection groups; Adopted multivariate logistic regression
      to analysis the combination effect of XRCC1 Arg399Gln gene polymorphism and
      accumulated illuminated dosefor micronucleus rate. Results: The accumulated
      illuminated dose in the reference group, the low detection group and the medium
      detection group were (23.44+/-15.23) , (21.76+/-2.56) , (24.22+/-18.61) mSv,
      respectively. There was no statistically significant difference among the groups
      (P>0.05) . Under the dominant inheritance mode, after adjusted age, smoking and
      drinking factors, the results suggested that XRCC1 Arg399Gln micronucleus medium
      detection group compared with the reference group, Arg399Gln-GG as reference,
      Arg399Gln-GA+AA decreased the occurrence of micronucleus (OR=0.175, 95%CI: 0.036
      0.848) . Arg194Trp and Arg280His did not affect the incidence of micronucleus
      (P>0.05) . Did not find the combination effect of XRCC1 Arg399Gln gene
      polymorphism and accumulated illuminated dose for micronucleus rate (P>0.05) .
      Conclusion:XRCC1 Arg399Gln gene polymorphism can affect the incidence of
      micronucleus, and carrying the XRCC1 Arg399Gln-GA+AA genotype is a protective
      factor of micronucleus's occurrence, but low dose ionizing radiation may not
      affect the occurrence of micronucleus independently.

PMID- 28511304
TI  - [Impact of carbon dioxide pneumoperitoneum in operating rooms on the health of
      medical staffs].
AB  - Objective: To evaluate the impact of CO(2) pneumoperitoneum in operating rooms on
      the health of medical staffs. Methods: In June 2016, the thirty-three medical
      staffs in operating rooms were chosen as the object of the research.Seventeen
      people who took part in the pneumoperitoneum operation were selected as a
      exposure group and sixteen people who took part in the laparotomy operation were
      selected as a control group.Vital signs and arterial blood gases of medical
      staffs in the two groups were both measured in pre-operation and post-operation.
      Occupational Health Questionnaires were conducted to collect information on age,
      weight and postoperative symptoms. The level of CO(2) in operating room was
      determined by a portable infrared CO(2) analyzer. Results: Compared with the
      control group, the concentration of CO(2) in the exposed group was higherat T(1),
      T(2) and T(3) (t=22.227, 13.583, 17.408, P<0.05) . Heart rates and PaCO(2) in the
      exposure group raised greatly (t=2.132, 2.129, P<0.05) , while pH decreased (t=
      3.015, P<0.05) . The differences between the two groups were statistically
      significant. Conclusion: The increase of mild acidosis and thesense of job
      burnout in medical staffs could be caused by CO(2) pollution in the operating
      rooms.

PMID- 28511305
TI  - [Value of heart rate as an optimum index in evaluating physical labor intensity].
AB  - Objective: To investigate the possibility of heart rate as an optimum index for
      evaluating physical labor intensity. Methods: From September to October, 2015, a
      total of 111 male young adults were selected as study subjects. A cycle ergometer
      was used for exercise at different intensities (20, 40, 60, 80, 100, 120, 140,
      160, and 180 W) , and the exercise at each intensity lasted for 6 minutes. The
      subjects wore the K4b2 portable cardiopulmonary function testing instrument for
      the real-time monitoring of heart rate (HR) , pulmonary ventilation volume (Ve) ,
      oxygen consumption (VO(2)) , and energy metabolic rate (E) . The origin software
      was used for correlation and regression analyses of HR, Ve, VO(2), and E
      collected at different intensities to establish Ve-HR, VO(2)-HR, and E-HR
      regression equations. Results: At different intensities, HR was positively
      correlated with Ve, VO(2), and E (r=0.8985, 0.8733, and 0.8973, all P<0.01) .
      There was a significant difference in the R(2) value of Ve-HR, VO(2)-HR, and E-HR
      regression equations (R(2)=0.8070, 0.7625, and 0.8049, all P <0.01) . The
      validation results showed that there was no significant difference between the
      calculated values and the measured ones (P>0.05) . Conclusion: HR can replace Ve,
      VO(2), and E and be used as an optimum index for evaluating physical labor
      intensity.

PMID- 28511306
TI  - [Relationship of job stress with job burnout and quality of work life in workers
      for offshore oil platforms].
AB  - Objective: To evaluate the current status of job burnout and qual ity of work
      life (QWL) in workers for offshore oil platforms, and to analyze the relationship
      of job stress with job burnout and QWL and the direct and indirect effects of job
      stress on QWL. Methods: Cluster random sampling was used to select 382 work-ers
      for 8 oil platforms of China National Offshore Oil Corporation in October 2015. A
      self-designed questionnaire was used to collect the individual characteristics of
      subjects. The Quality of Work Life Scale (QWL7-32) , Occupa-tional Stress
      Inventory-Revised Edition (OSI-R) , and Maslach Burnout Inventory-General Survey
      (MBI-GS) were used to investigate the QWL, job stress, and job burnout of
      subjects. Results: Among all the workers for offshore oil platforms, 87.2% had
      mild job burnout. The total QWL score was 116.01 +/- 16.73; 8.3% of the workers
      had poor QWL, and 68.5% had moderate QWL. QWL was reduced with heavier task,
      vaguer task, and increasing mental stress and physical stress (P<0.05) , and
      increased with more social support (P<0.05) . Job stress had di-rect and indirect
      effects on QWL; stress reaction had the most effect on QWL (total effect size 
      0.509) , followed by social support (total effect size 0.444) . Conclusion: Most
      workers for offshore oil platforms have mild job burn-out and moderate QWL. Job
      stress is associated with job burnout and QWL, and stress reaction and social
      support have relatively high influence on QWL.

PMID- 28511307
TI  - [Influence of long-time video operation on hemodynamics of the retrobulbar
      arteries in operators].
AB  - Objective: To investigate the influence of long-time video operation on
      hemodynamics of the retrobulbar arteries in operators. Methods: From March to
      October, 2015, a total of 120 soldiers for office work engaged in video
      surveillance were enrolled as study group, and 155 fire fighters were enrolled as
      control group. The incidence of eye discomfort was compared between the two
      groups. Color Doppler ultrasound was used to measure and compare the peak
      systolic velocity (PSV) , end-diastolic velocity (EDV) , and resistance index
      (RI) of the central retinal artery (CRA) and the short posterior ciliary artery
      (SPCA) , and the correlation of video operation time with the hemodynamic
      parameters of the retrobulbar arteries was analyzed. Results: The study group had
      a significantly higher incidence rate of eye discomfort than the control group
      (P<0.05) . Compared with the control group, the study group had significant
      reductions in the PSV and EDV of the CRA and the SPCA and a significant increase
      in the RI of the CRA (P<0.05) . Video operation time was negatively correlated
      with the PSV and EDV of the CRA and the SPCA (r=-0.61, -0.54, -0.65, and-0.68,
      all P<0.05) and positively correlated with the RI of the CRA and the SPCA (r=0.56
      and 0.63, P<0.05) . Conclusion: Long-time video operation can increase the
      incidence of eye discomfort and lead to increased blood resistance of the CRA and
      the SPCA and reduced retinal perfusion.

PMID- 28511308
TI  - [Blood-borne occupational exposure and protection in medical staff of a
      traditional Chinese medicine hospital].
AB  - Objective: To investigate blood-borne occupational exposure and related
      protection in the medical staff of a traditional Chinese medicine hospital, and
      to provide a reference for reducing the risk of blood-borne occupational
      exposure. Methods: Forty-eight medical workers with blood-borne occupational
      exposure in 2015 were selected to analyze the incidence of blood-borne
      occupational exposure, influencing factors, operations that caused blood-borne
      occupational exposure, pathogens, and occupational protection. Results: The
      incidence rate of blood-borne occupational exposure in the medical staff of the
      traditional Chinese medicine hospital in 2015 was 3.30% (48/1 455) , and the
      frequency was 0.04 time/person/year. The workers with blood-borne occupational
      exposure were mostly nurses, females, workers aged <30 years, workers with <5
      working years, and workers with a junior professional title. There was a
      significant difference in the incidence rate of blood-borne occupational exposure
      between workers with different ages and working years. The main way of blood
      borne occupational exposure was sharp injury (96.08%) . The main operations that
      caused blood-borne occupational exposure were covering or separating the syringe
      needle after injection and disposing used sharp instruments. The main exposure
      site was the hand (96.08%) , with the thumb and index finger for the left hand
      and the middle finger and index finger for the right hand; there was no
      significant difference in the exposure site distribution between the two hands
      (P<0.05) . The main pathogen that caused blood-borne occupational exposure was
      hepatitis B virus (68.96%) . The rate of correct local treatment for blood-borne
      occupational exposure was 88.24%. The rate of prophylactic medication was 74.51%,
      and hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine was the main way,
      followed by HBIG. In all workers with blood-borne occupational exposure, 62.74%
      did not wear gloves. Conclusion: The medical workers with few working years have
      a high risk of blood-borne occupational exposure, so the training on protection
      against blood-borne occupational exposure should be strengthened to reduce the
      risk of blood-borne occupational exposure and infection.

PMID- 28511310
TI  - [Report of 6 cases of malignant arrhythmia induced by acute poisoning].

PMID- 28511309
TI  - [Effect of occupational exposure on job burnout in nurses].
AB  - Objective: To investigate the effect of occupational exposure on job burnout in
      nurses, and to analyze the mediating effect of negative emotion between
      occupational exposure and job burnout and the regulatory effect of supervisor
      support on occupational exposure and negative emotion. Methods: From September to
      December, 2015, simple random sampling was used to select 543 nurses from six
      tertiary hospitals in Zhejiang Province, China. The questionnaires consisted of
      occupational exposure risk questionnaire, negative emotion questionnaire,
      supervisor support questionnaire, and job burnout questionnaire. Results: The
      total score of occupational exposure risk in nurses was 11.43+/-7.19; the score
      of emotional exhaustion was 3.19+/-1.24, the score of low sense of personal
      accomplishment was 3.02+/-1.21, and the score of sense of working indifference
      was 2.24+/-1.06. There were significant differences in occupational exposure
      score between nurses with different sexes (t=2.61, P<0.01) and working years
      (F=4.49, P<0.01) . There were significant differences in the scores of emotional
      exhaustion and low sense of personal accomplishment in nurses with different
      sexes (t=5.25, P<0.001) and working years (t=-3.48, P<0.01) . Occupational
      exposure had positive effects on negative emotion (beta=0.41, P<0.05) , emotional
      exhaustion (beta=0.47, P<0.05) , sense of working indifference (beta=0.42,
      P<0.05) , and low sense of personal accomplishment (beta=0.17, P<0.05) . Negative
      emotion had a partial mediating effect between occupational exposure and
      emotional exhaustion (total effect size 30.5%, P<0.05) and between occupational
      exposure and sense of working indifference (total effect size 37.1%, P<0.05) .
      Negative emotion had a complete mediating effect between occupational exposure
      and low sense of personal accomplishment (beta=0.08, P>0.05) . Supervisor support
      negatively regulate the effects of occupational exposure and negative emotion
      (F=21.73, P<0.001) . Conclusion: In nurses, occupational exposure has a direct
      positive effect on job burnout and indirectly influences job burnout via negative
      emotion. Supervisor support can reduce the negative impact of occupational
      exposure on negative emotion.

PMID- 28511311
TI  - [Analysis of misdiagnosis of common occupational toxic abdominal pain].

PMID- 28511312
TI  - [Size exclusionchromatography-high-performance liquid chromatography-inductively
      coupled plasma mass spectrometry for measuring the stability of cadmium
      telluridequantum dots].
AB  - Objective: To investigate the peak time and peak area of elements in cadmium
      telluride quantum dots (CdTe QDs) using size exclusion chromatography-high
      performance liquid chromatography-inductively coupled plasma mass spectrometry,
      as well as the biological stability of CdTe QDs in vivo and in vitro. Methods:
      Transmission electron microscope and ultraviolet fluorescence were used for
      characterization and synthesis of water-soluble CdTe QDs, and CdTe QDs were added
      to double-distilled water, mobile phase, or bovine serum medium to observe the
      change in stability after different periods of time. CdTe QDs were injected into
      the vein of mice, and the changes in the morphology of CdTe QDs in serum and the
      liver were measured at 1, 24, and 72 hours after exposure. Size exclusion
      chromatography-high-performance liquid chromatography was used for the elution of
      the compounds in the solution based on their volume, and then inductively coupled
      plasma mass spectrometry was performed for the eluent. The flow time of (114)Cd
      and (130)Te and molar ratio were used for qualitative analysis of CdTe QDs, and
      the peak area was used to judge whether CdTe QDs were degraded. Results: CdTe QDs
      were diluted to a concentration of 0.5 mmol/L with double-distilled water and
      then placed in a dark place at room temperature; CdTe QDs were completely
      degraded after 60 minutes. CdTe QDs were diluted to a concentration of 0.005
      mmol/L with a mobile phase, and the peak of CdTe QDs was not detected. After CdTe
      QDs were placed in a dark place at room temperature for 48 hours at a
      concentration of 0.005 mmol/L in bovine serum mediumin vitro, the peak area of
      (114)Cd was 6179841-7346084, and the peak area of (130)Te was 1077913-1191066.
      CdTe QDs had the highest peak area at 1 hour after exposure, and the peak areas
      of (114)Cd and (130)Te were 18183894 and 25187987, respectively. CdTe QDs were
      quickly degraded in the liver; at 1 hour after exposure, the degradation products
      of CdTe QDs containing Cd were observed in liver tissue homogenate, and CdTe QDs
      were largely degradedat 24 hours. Conclusion: This method can be used to
      investigate the biological stability of CdTe QDs. CdTe QDs are degraded in the
      liver and produce Cd(2+), which may cause toxic reaction.

PMID- 28511313
TI  - [Determination of thiocyanate within human urine by ion chromatography method].
AB  - Objective: To establish ion chromatography method to determine thiocyanate within
      urine of workers who were exposed to cyanide. Methods: After the workers work,
      used 50 ml centrifuge tube to collect the urine of workers about 20 ml.The urine
      were tested by centrifugation, dilution and filtration by C(18) column,
      thiocyanate was separated by AS(16) and mobile phase elution by KOH, detected by
      electrical circuitryconductivity detector, quantitative by the standard curve
      method. Results: The linear correlation coefficient of thiocyanate within the
      range of 0.1-5.0 MUg/ml was more than 0.999. The method detection limit was
      0.11MUg/ml (in 1ml urine) , the method quantitative limit was 0.35 MUg/ml. The
      method recoveries were 95.1%-99.7%. The within-day precision range was 0.54%
      2.05%, The between-run precision range was 2.06%-5.09%. Sample stability test
      showed that thiocyanate samples could be stored for 5 days at room temperature
      and 7 days at 4 C, could be stored for 14 days at-20 C. Conclusion: The technical
      indicator of method compliance with rule of Guide for establishing occupation
      health standards-Part 5: determination methods of chemicals in biological
      materials (GBZ/T 210.5-2008) , the method applies to workers who were exposed to
      cyanide.

PMID- 28511314
TI  - [Determination of cadmium in human urine by colloidal gold immunochromatographic
      assay].
AB  - Objective: To establish the method of colloidal gold immunochrom atographic assay
      for detecting cadmium ions rapidly. Methods: The anti-cadmium ion monoclonal
      antibody-gold conjugate was labeled on the binding pad, cadmium ion hapten and
      goat anti-mouse IgG were coated on nitrocellulose membrane as the detection line
      (T line) and quality control line (C line) respectively. The sample pad,
      colloidal gold bonding pad, nitrocellulose membrane and absorption pad were
      orderly assembled on the PVC board to cut into a test paper strip. The
      qualitative results of the assay were visualized in color. Results: When
      detecting the human urine cadmium ions, the results were tested qualitativly
      within 15 minutes. The detection limit was 30 MUg/L. No cross-reactivity with
      other heavy metal ions. The test paper strip could be stored at 4 C for 3 months.
      Conclusion: The method has the advantages of low cost, strong specificity, good
      stability and reliable results, and is suitable for rapid screening of cadmium
      poisoning of enterprise and occupational health.

PMID- 28511315
TI  - [A cost-benefit analysis of occupational disease reporting in China].
AB  - Objective: To perform a cost-benefit analysis of the occupational disease
      reporting system in China, and to provide a basis for effective resource
      allocation. Methods: The data on the cost of occupational diseases were collected
      from China Health Statistics Yearbook 2013, the estimated benefit data were
      collected from published articles in China and foreign countries, and the
      probability data were collected from the occupational diseasereports published by
      health and family planning administrative departments. Adecision-making tree was
      used for the cost-benefit analysis. Results: The estimated cost of occupational
      disease reporting was about 102.47 million yuan/year, consisting of a cost of
      reporting in national medical institutions of 1.25 million yuan/year, a
      management cost of 30.35 million yuan/year, a management cost in local public
      health institutions of 69.80 million yuan/year, a management cost in national
      public health institutions of 370 thousand yuan/year, and a cost of construction
      and maintenance of reporting system of 700 thousand yuan/year. The results of the
      decision tree analysis showed that when an occupational disease monitoring system
      was established, the incremental input for occupational disease monitoring and
      prevention/control was 2.1 billion yuan/year, the output was 6.5 billion
      yuan/year, and the benefit of occupational disease reporting system was 4.4
      billion yuan/year. Conclusion: The benefit of occupational disease reporting
      system depends on the cost-benefit of occupational disease prevention and control
      measures, and proper prevention and control measures are extremely important for
      improving the benefit of occupational disease reporting system.

PMID- 28511316
TI  - [Research progress on Lgr5 protein].

PMID- 28511317
TI  - [Research progress on the p-phenylenedinamine toxicity and effect on health].

PMID- 28511318
TI  - [research progress on biomarkers of diphenylmethane diisocyanate].

PMID- 28511319
TI  - [Status of diagnosis and treatment of non-ST-segment elevation acute coronary
      syndrome in China].

PMID- 28511320
TI  - [Guideline and consensus for the management of patients with non-ST-elevation
      acute coronary syndrome(2016)].

PMID- 28511321
TI  - [Impact of CYP2C19 genotype and platelet function on clinical outcome in coronary
      atherosclerotic heart diseases patients received clopidogrel post percutaneous
      coronary intervention].
AB  - Objective: To analyze association of CYP2C19 genotype and platelet function
      phenotype and their impact on clinical outcomes including bleeding events of
      coronary artery disease(CAD) patients received clopidogrel post percutaneous
      coronary intervention(PCI). Methods: Coronary atherosclerotic heart diseases
      patients underwent elective PCI and coronary stent implantation in Fuwai hospital
      were prospectively enrolled during May 2012 to April 2013. Patients were assigned
      into groups by genotype of CYP2C19 (extensive metabolizers, intermediate
      metabolizers, and poor metabolizers) and phenotype of platelet function
      (clopidogrel responders, semi-responders, and non-responders). The rates of major
      adverse cardiovascular events, combined cardiovascular events, and bleeding
      events were recorded during a at least 12 months follow-up period and compared
      among above defined groups. The association between genotype or phenotype and
      clinical outcome was assessed using multivariable Cox regression hazards model.
      Results: Three hundred and eighty patients received coronary stent implantation
      and met the inclusion criteria of the study, including 157(41.3%) clopidogrel
      extensive metabolizers, 176(46.3%) intermediate metabolizers, and 47(12.4%) poor
      metabolizers according to the genotype grouping; 98(25.8%) were responders to
      clopidogrel, 149(39.2%) were semi-responders, and 133 (35.0%) were non-responders
      according to the phenotype grouping. Three hundred and seventy-six patients
      accomplished follow-up. The highest combined cardiovascular events rate was
      observed in the poor metabolizers (34.0%(16/47)) as compared to the intermediate
      metabolizers (19.0%(33/174), P=0.026) and the extensive metabolizers
      (15.5%(24/155), P=0.005). The highest bleeding events rate was observed in the
      clopidogrel responders (33.7%(33/98)) as compared to the semi-responders
      (18.9%(28/149), P=0.008) and non-responders (17.7%(23/130), P=0.008). In
      multivariable Cox regression analysis, the adjusted risk of cardiovascular death,
      acute myocardial infarction, stent embolism, target lesion revascularization and
      angina onset was 2.305 times higher in clopidogrel poor metabolizers than in
      extensive and semi-metabolizers (95%CI=1.208-4.399, P=0.011). The adjusted HR for
      bleeding events was 0.540 (95%CI=0.321-0.909, P=0.021) among semi-responders vs.
      responders, was 0.52 (95%CI=0.301-0.905, P=0.021) among non-responders vs.
      responders during the 12 months follow-up period. Conclusions: Among CAD patients
      underwent stenting and clopidogrel treatment, poor CYP2C19 metabolizers group
      carries a significantly higher risk for combined cardiovascular events than in
      extensive metabolizers group, while clopidogrel responders patients are at
      significantly higher risk for bleeding as compared to the semi-responders and non
      responders.

PMID- 28511322
TI  - [Interaction between APOB gene polymorphism and risk factors in coronary heart
      disease patients without lipid-lowering treatment].
AB  - Objective: To investigate the association between APOB gene R532W polymorphism
      and the risk of coronary heart disease (CHD) in patients without lipid-lowering
      treatment and to analyze the interactions between the variation of R532W and
      different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according
      to coronary artery angiography (CAG) and/or coronary computed tomography
      angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD
      patients and 772 age- and sex-matched non-CHD controls, who never accepted any
      lipid-lowering treatments, were collected. R532W was genotyped by HumanExome
      BeadChip at BGI and strict quality control was made. Firstly, the association
      between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG,
      AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was
      explored. Then, the interactions between the variation of this loci and risk
      factors related to CHD were investigated. Results: (1) Total cholesterol (TC)
      levels were significantly lower in AA genotype than in GA genotype in the total
      cohort and non-CHD controls, but was similar among the 3 genotypes in CHD
      patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD
      patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532
      polymorphism was related to the incidence of CHD in the dominant model, and A
      allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI
      0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W
      polymorphism had positive interactions with hypertension (1.452) and smoke
      (1.077), while negative interaction with diabetes (0.553) in the occurrence of
      CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese
      north Han population. A-allele carries of R532W loci is linked with reduced risk
      of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a
      positive additive interaction with hypertension and smoke, while a negative
      additive interaction with diabetes mellitus in the occurrence of CHD.

PMID- 28511323
TI  - [Impact of symptom onset to first medical contact time on the prognosis of
      patients with acute ST-segment elevation myocardial infarction].
AB  - Objective: To investigate the impact of symptom onset to first medical contact
      (SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation
      myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI
      patients, who were hospitalized to our hospital and received primary percutaneous
      coronary intervention(PCI) from August 2011 to April 2016, were retrospectively
      analyzed. The patients were divided into <=90 min group (201 cases) and >90 min
      group (140 cases) according to the SO-to-FMC time. The treatment time, mortality
      and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were
      analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of
      MACCE during the post-discharge follow-up period were analyzed by binary logistic
      regression analysis. The predictor of 4.5-year mortality after PCI was analyzed
      by multivariate Cox regression analysis. Methods The door to balloon time
      (104(88, 125) min vs. 111(92, 144)min, P=0.023), first medical contact to balloon
      time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to
      balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001)were all
      significantly shorter in the <=90 min group than in>90 min group. The 30-day
      mortality (2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89
      (5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post
      discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year
      cumulative mortality(3.00% vs. 11.20%, P=0.007) after PCI were significantly
      lower in the <=90 min group than in the >90 min group. Moreover, the 4.5-year
      incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post
      discharge follow-up period was significantly higher in the <=90 min group than in
      the >90 min group. In-hospital mortality was similar between the two groups
      (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results: The door to balloon time
      (104(88, 125) min vs. 111(92, 144)min, P=0.023) , first medical contact to
      balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset
      to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001) were all
      significantly shorter in the <=90 min group than in >90 min group. The 30-day
      mortality(2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality
      (2.89(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the
      post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5
      year cumulative mortality (3.00% vs. 11.20%, P=0.007) after PCI were
      significantly lower in the <=90 min group than in the >90 min group. Moreover,
      the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the
      post-discharge follow-up period was significantly higher in the <=90 min group
      than in the >90 min group. In-hospital mortality was similar between the two
      groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results of binary logistic
      regression analysis showed that the SO-to-FMC time >90 min was the risk factor of
      1-year mortality(OR=2.90, 95%CI 1.22-6.92, P=0.016) and 1-year incidence of MACCE
      (OR=5.19, 95%CI 1.21-22.20, P=0.026) during the post-discharge follow-up period.
      Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min
      was the risk factor of 4.5-year mortality after PCI in patients with STEMI
      (HR=2.88, 95%CI 1.10-7.53, P=0.031). Conclusion: Shorting the SO-to-FMC time can
      significantly reduce the treatment time of STEMI patients, short and long-term
      mortalities and the incidence of MACCE, and improve the prognosis of patients
      with STEMI.

PMID- 28511324
TI  - [Social support status and related influential factors of patients with acute
      coronary syndrome].
AB  - Objectives: To investigate the social support status, related influential factors
      and the impact on one year outcome in patients with acute coronary syndrome
      (ACS), our data might be helpful to provide basis for making new treatment
      strategy aimed at improving social support for patients with ACS. Methods: From
      January 2013 to June 2014, a total of 778 hospitalized patients with ACS were
      enrolled in the study. All patients completed enhancing recovery in coronary
      heart disease patients social support inventory(ESSI), general anxiety disorder
      scale(GAD-7), patient health questionnaire(PHQ-9), short-form 12 health survey
      questionnaire(SF-12), sleep questionnaire and demographic questionnaire within 7
      days after admission and at 6 months and one year post discharge. Multiple linear
      regressions were performed to analyze factors that influenced the social support.
      Results: The total score of social support was 17.08+/-3.61, 17.72+/-3.04, and
      17.76+/-3.05 respectively in patients with ACS at baseline, 6 months and 12
      months after discharge. Patients had a higher point of social support at 6 months
      (t=-2.69, P<0.01) and 12 months (t=-2.86, P<0.01) after discharge than at
      baseline. Multiple regression analysis for baseline data identified five
      significant predictors of low social support status: workers or farmers (t=2.82,
      P<0.01), low family monthly income (t=2.42, P<0.05), anxiety (t=-3.66, P<0.01),
      depression (t=-3.22, P<0.01) and low quality of life (t=4.38, P<0.01).
      Conclusions: Social support of patients with ACS is lower in China, and there are
      significant relationships between low social support and occupation, economic
      status, anxiety, depression, quality of life of ACS patients.

PMID- 28511325
TI  - [Feasibility of the 2014 European guidelines risk prediction model for sudden
      cardiac death in hypertrophic cardiomyopathy in Chinese patients].
AB  - Objective: Exploring the feasibility of the 2014 European Society of
      Cardiology(ESC)guideline's risk prediction model for sudden cardiac death in
      hypertrophic cardiomyopathy (HCM Risk-SCD) in Chinese patients. Methods: The
      study population consisted of a consecutive cohort of 172 Chinese patients with
      HCM without prior sudden cardiac death (SCD) event who were in patients in
      Nanjing Drum Tower Hospital from December 2010 to October 2015.The endpoint event
      was a composite of SCD and appropriate implantable cardioverter-defibrillator
      (ICD) therapy.Clinical data were collected to calculate the 5-year SCD risk using
      the HCM Risk-SCD formula and to observe the actual risk during the follow
      up.Receiver operating characteristic curves (ROC) and the area under curve (AUC)
      were calculated for the HCM Risk-SCD and risk stratification methods of the 2011
      American Heart Association (AHA) guideline. Results: During follow-up of (2.69+/
      1.36) years, five patients achieved the endpoint event.The predicated rate of SCD
      event using HCM Risk-SCD was (2.36+/-1.73)%, (1.93+/-0.78)%, (5.18+/-0.65)%,
      (8.77+/-2.38)% for all patients, low-risk group, medium-risk group and high-risk
      group respectively.However, the actual rate of SCD event was 2.91%, 1.27%, 25.00%
      and 14.29%, respectively.The AUC of 2014 ESC guideline and 2011 AHA guidelinewas
      0.93(95%CI 0.85-1.00) vs. 0.87(95%CI 0.75-0.98). Conclusion: The predicated rate
      of SCD event calculated by HCM Risk-SCD is lower than actual rate of SCD, but the
      prediction efficiency and indication for ICD implantation of HCM Risk-SCD are
      better than that of 2011 AHA guideline.

PMID- 28511326
TI  - [Comparison of aortic annular diameter defined by different measurement
      mordalities before transcatheter aortic valve implantation].
AB  - Objective: To compare aortic annular diameter measured by transthoracic
      echocardiography (TTE), transesophageal echocardiography (TEE), and multislice
      computed tomography (MSCT) in patients with severe aortic stenosis, and to
      evaluate the impact on selection of prosthetic valve type in transcatheter aortic
      valve implantation (TAVI). Methods: Clinical data of 138 patients with severe
      aortic stenosis referred for TAVI between January 2014 and June 2016 in our
      hospital were retrospectively analyzed.The difference of aortic annular diameter
      measured by TTE, TEE, and MSCT were compared.TTE was performed after TAVI to
      evaluate the accuracy of measurement before TAVI. Results: (1) Aortic annular
      diameter was (23.37+/-2.22) mm by TTE and (23.52+/-1.70) mm by TEE (P=0.12).
      Pearson correlation analysis showed that aortic annular diameter measured by TTE
      was correlated to that measured by TEE (r=0.87, P<0.05). (2)The long-axis
      diameter and the short-axis diameter measured by MSCT multiplanar reconstruction
      were significantly different ((27.86+/-2.87) mm vs. (21.91+/-2.53) mm, P<0.05).
      There was no significant difference between the mean of the long- and short-axis
      diameters and the diameter derived from cross-sectional area by MSCT ((24.92+/
      2.38) mm vs. (24.84+/-2.25) mm, P=0.08). However, the diameter derived from the
      circumference ((25.35+/-2.34) mm) was significantly larger than the mean of the
      long- and short-axis diameters and the diameter derived from cross-sectional area
      by MSCT, and the difference were (0.43+/-0.62) mm and (0.51+/-0.62) mm
      respectively(both P<0.05). (3) Measurements of the aortic annulus diameter by
      MSCT including the mean of the long- and short-axis diameters, diameter derived
      from cross-sectional area, and diameter derived from the circumference were
      larger than the measurement by TTE and TTE (all P<0.05). (4) Implantation was
      successful in all patients.Moderate to severe paravalvular leakage was detected
      in 3 patients at 7 days post TAVI, and 1 patient developed severe prosthetic
      valve restenosis at 6 months post TAVI and received valve-in-valve implantation.
      Conclusions: In severe aortic stenosis patients referred for TAVI, the aortic
      annular diameter derived from TTE and TEE measurements are smaller than that from
      MSCT.In the absence of a gold standard, selection of prosthetic valve type in
      TAVI procedure should rely on comprehensive considerations, which is of
      importance to get good clinical results for severe aortic stenosis patients
      underwent TAVI.

PMID- 28511327
TI  - [Determination of iodine content in the left ventricular myocardium of healthy
      subjects using dual-source dual-energy CT myocardial first perfusion imaging: a
      preliminary study].
AB  - Objective: To analyze the normal value of the iodine content in the left
      ventricular myocardium of healthy subjects and to observe if there is a segmental
      differences on iodine distribution by using the second generation dual-source
      dual-energy computed tomography myocardial first perfusion imaging. Methods: In
      this retrospective study, 42 healthy subjects, who admitted to our department
      between January to June 2016, with normal second generation dual-source dual
      energy computed tomography and coronary CT angioghphy (CTA), electrocardiogram
      (ECG) results, normal cardiac, hepatic, renal function, normal myocardial enzymes
      results were enrolled, data from 38 out of 42 subjects with satisfactory image
      quality were analyzed using Siemens Dual Energy-Heart PBV image processing
      software.In accordance with the standards of the American Heart Association
      myocardial 17 fractionation method, content of iodine was measured at different
      segmental left ventricular myocardium and aorta (left coronary artery from the
      opening level). The standardized containing iodine value (nIC) was calculated.
      Results: The iodine content of left ventricular myocardium in normal subjects was
      3.1-7.8 mg/ml.The nIC of myocardium from 1st to 17th segments was 0.28+/-0.06,
      0.31+/-0.07, 0.30+/-0.07, 0.30+/-0.04, 0.28+/-0.04, 0.29+/-0.05, 0.29+/-0.01,
      0.30+/-0.07, 0.31+/-0.07, 0.27+/-0.06, 0.28+/-0.08, 0.28+/-0.07, 0.29+/-0.08,
      0.31+/-0.07, 0.27+/-0.06, 0.29+/-0.06 and 0.21+/-0.07, respectively.The nIC of
      the 17th segment was the lowest and was significantly lower than in other
      segments (all P<0.05), the nIC was similar among the rest 16 segments (all
      P>0.05). Conclusion: The normal iodine content range in left ventricle myocardium
      is 3.1-7.8 mg/ml, and the lowest iodine content is detected in the apex and which
      is significantly lower than the other left ventricular segments.

PMID- 28511328
TI  - [Effects of apolipoprotein E deficiency on sphingosine-1-phosphate distribution
      in plasma and lipoproteins of mice].
AB  - Objective: To investigate the effects of apolipoprotein E deficiency (Apo E(-/-))
      on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice.
      Methods: Five male or female Apo E(-/-) or wild type (WT) mice were fed with chow
      diet and sacrificed at 32-week-age and plasma was collected. The constituents of
      lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL),
      high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein
      concentration of constituents was detected by BCA protein quantitative kit, and
      the S1P concentration in plasma and various lipoprotein constituents was detected
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot was
      used to determine the plasma, liver, and kidney protein expression of
      apolipoprotein M(Apo M), which is considered as specific ligand of S1P.The S1P
      concentration in plasma and various constituents of lipoprotein in the Apo E(-/-)
      mice was compared to respective WT mice. Results: (1)Plasma S1P content was
      significantly higher in the Apo E(-/-) groups than that of WT groups (male:
      (535.7+/-78.5)nmol/L vs. (263.3+/-22.0)nmol/L; female: (601.1+/-64.0)nmol/L vs.
      (279.0+/-33.9)nmol/L; all P<0.01). (2) Compared with WT mice, S1P content in non
      HDL(LDL+ VLDL) was significantly higher in Apo E(-/-) mice (male: (504.9+/
      52.8)nmol/L vs. (28.7+/-9.0)nmol/L; female: (427.7+/-27.4) vs. (27.8+/
      4.7)nmol/L; after standardization of protein concentration, male: (385.0+/
      41.2)pmol/mg protein vs. (71.4+/-6.6)pmol/mg protein; female: (330.2+/
      22.0)pmol/mg protein vs. (67.2+/-12.1)pmol/mg protein; all P<0.01). (3) The
      expression of Apo M in plasma, liver and kidney was significantly higher in Apo
      E(-/-) groups than that of WT groups(all P<0.05). Conclusion: The deficiency of
      Apo E could lead to upregulated S1P expression in the non-HDL, the underlying
      mechanism might be the increased transfer of HDL into the non-HDL by Apo M-S1P.

PMID- 28511331
TI  - [Percutaneous ventricular restoration for patients with left ventricular aneurysm
      and heart failure after myocardial infarction:4 cases report].

PMID- 28511330
TI  - [Successful thrombolysis treatment in one patient with acute cerebral infarction
      after atrial fibrilation catheter ablation].

PMID- 28511329
TI  - [Therapeutic effect of combined use of FGF1-loaded nano-liposomes and ultrasound
      targeted microbubble destruction technique on treating rats with experimental
      diabetic cardiomyopathy].
AB  - Objective: The therapeutic effect of acid fibroblast growth factor 1(FGF1) on
      rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes
      combined with ultrasound-targeted microbubble destruction technique (UTMD).
      Methods: The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion
      method combined with lyophilization technique.TypeIdiabetes model was induced by
      intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD
      rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group
      (saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded
      nano-liposomes plus UTMD group (n=15 each). After two weeks of intervention
      followed by 2 weeks intervention stop, all rats underwent cardiac
      catheterization, and the left ventricular end-systolic pressure (LVESP), left
      ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate
      of left ventricular pressure (LV+/-dp/dtmax) were measured.Then, the rats were
      sacrificed and myocardial tissue were obtained for Masson trichrome staining,
      TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify
      myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and
      myocardial microvascular density (MVD). Results: (1)Scanning electron microscope
      results revealed good morphology and FGF1 encapsulation efficiency (84.3+/-2.8)%
      with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The
      hemodynamic evaluation showed that LVESP, LV + dp/dt(max) and LV -dp/dt(max) were
      all significantly higher, while LVEDP was significantly lower in the FGF1-loaded
      nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano
      liposome group(all P<0.05). (3)The Masson trichrome staining demonstrated that
      CVF was significantly higher in all DCM groups than in control group and was
      significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM
      group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (4)The
      CD31 immunohistochemical staining results showed that MVD was significantly lower
      in all DCM groups than in control group and was significantly higher in the FGF1
      loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1
      nano-liposome group (all P<0.05). (5)The TUNEL results showed that apoptotic
      index was significantly higher in all DCM groups than in control group and was
      significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM
      group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05).
      Conclusion: FGF1 nano-liposomes combining with UTMD technique can significantly
      improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance
      myocardial MVD in DCM rats.

PMID- 28511332
TI  - [Kounis sysdrome secondary to crucian allergy:a case report].

PMID- 28511333
TI  - [Left main artery embolism caused by left atrial myxoma:a case report].

PMID- 28511334
TI  - [Meigs syndrome presenting with isolated pericardial effusion: a case report].

PMID- 28511335
TI  - [Gene mutations of proprotein convertase subtilisin/kexin type 9 and low density
      lipoprotein-cholesterol].

PMID- 28511336
TI  - [Research update on the regulation between epicardial adipose tissue and coronary
      artery disease].

PMID- 28511337
TI  - [Research update on the regulation of monocyte/macrophages by Kruppel-like
      factors in atherosclerosis].

PMID- 28511338
TI  - [Research update on the hybrid treatment of atrial fibrillation].

PMID- 28511339
TI  - Patterns of disease occurrence and management, and public health issues among
      Korean populations based on information and experiences obtained by field
      epidemiological studies in various situations with episodic stories never been
      told.

PMID- 28511340
TI  - Review of brucellosis in Nepal.

PMID- 28511341
TI  - In vivo and molecular docking studies using whole extract and phytocompounds of
      Aegle marmelos fruit protective effects against Isoproterenol-induced Myocardial
      infarction in rats.
AB  - Myocardial infarction (MI) is a leading major health problem with increased
      morbidity and mortality worldwide. The present study investigates isoproterenol
      (ISO) induced MI and the beneficial role of Aegle marmelos fruit extract (AMFE)
      in rats. Our results indicated the significant augmentation of plasma nitric
      oxide (NOx) levels, C-reactive protein (CRP), homocysteine, apolipoprotein B (apo
      B), cardiac tissue lipid peroxidation and liver 3-hydroxy-3 methyl glutaryl CoA
      (HMG-CoA) reductase activity in ISO treated rats (85mg/kg b.wt) with a
      concomitant decrease in plasma apolipoprotein A1 (apo-A), lipase activity,
      paraoxonase-1 activity and cardiac tissue taurine levels when compared with
      controls. However, pretreatment of ISO administered rats with AMFE (150mg/kg
      b.wt/day for 45 days) markedly brought the observed alterations toward near
      normal level indicating its protective role against MI. Further, we have extended
      our studies to study the interaction of important phytocompounds, marmesin,
      marmin, umbelliferone and impertonin, present in AMFE with key enzymes, HMG-CoA
      reductase, iNOS, lipoprotein lipase and paraoxonase using AutoDock4. Molecular
      docking analysis indicated that HMG-CoA reductase, inducible nitric oxide
      synthase (iNOS) and lipoprotein lipase formed a strong enzyme ligand complex with
      impertonin. While the marmesin showed strong interaction with paraoxonase enzyme.
      In conclusion, our results suggest that AMFE acts as a strong protective agent
      against ISO-induced MI, and the bioactive compounds are responsible for this
      protective action which is confirmed by molecular docking studies.

PMID- 28511342
TI  - Combination of flavonoids from Oroxylum indicum seed extracts and acarbose
      improves the inhibition of postprandial blood glucose: In vivo and in vitro
      study.
AB  - The combined effect of Oroxylum indicum seed extracts (OISE) or major flavonoids
      from OISE and acarbose on reducing postprandial blood glucose (PBG) levels was
      investigated in vitro and in vivo. In vitro, the IC50 values of OISE and
      baicalein against alpha-glucosidase were 43.4+/-0.731MUgmL-1 and 25.9+/
      0.412MUgmL-1 respectively. A combination of acarbose with OISE or baicalein
      synergistically inhibited rat intestinal alpha-glucosidase. The combination index
      (CI) values for acarbose with OISE ranged from 0.33 to 0.75, suggesting a
      synergistic but not additive effect. OISE was determined to be a non-competitive
      inhibitor of maltose-hydrolyzing activity. In vivo, OISE were administered to
      normoglycemic and diabetic mice, either alone or in combination with acarbose. At
      doses between 50 and 200mgkg-1, OISE enhanced the efficacy of acarbose by up to 5
      fold. These results demonstrated that OISE enhances the efficacy of acarbose in
      vivo, and that the combination of OISE and acarbose displayed a synergistic
      effect in vitro. Therefore, OISE can be used to design dietary supplements to
      treat diabetes.

PMID- 28511343
TI  - Restoration of miR-143 expression could inhibit migration and growth of MDA-MB
      468 cells through down-regulating the expression of invasion-related factors.
AB  - INTRODUCTION: Breast adenocarcinoma is the second common cancer in women the
      incidence of which is increasing in many countries, especially in developing
      companies. In this study, miRNA143 has been replaced by vector based microRNA-143
      in breast adenocarcinoma cells (MDA-MB-468) and its anti-cancer effects on breast
      adenocarcinoma cells have been evaluated. METHODS: The pCMV-MIR-143 vector was
      transfected into MDA-MB-468 cells via JetPEI transfection reagent. The
      transfected cells were selected by IC50 concentration of Geneticin antibiotic
      (G418) after a 2-week treatment. To evaluate the effect of miR-143 on the
      inhibition of migration, scratch wound healing assay was performed. Then, the
      expression level of miR-143, Kras, Vimentin, CXCR4, MMP9 and E-Cadherin were
      measured by the qRT-PCR method. RESULTS: Results of MTT and wound healing assays
      showed that miR-143 inhibited cell growth and cell migration in miR-143 induced
      cell line compared with control group. The result of gene expression showed that
      miR-143 reduced Kras, Vimentin, CXCR4 and MMP9 expression, and increased E
      Cadherin expression in miR-143 replaced cells compared to control cells.
      CONCLUSION: The results showed that miRNA-143 plays an important role in cell
      growth and migration during breast cancer development and metastasis and it can
      be a candidate as a therapeutic molecule in microRNA replacement therapy of
      breast adenocarcinoma.

PMID- 28511344
TI  - Anti-inflammatory effects of trans-anethole in a mouse model of chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung
      disease that is generally characterized by progressive and irreversible airflow
      obstruction and alveolar destruction. Long-term treatment with current
      medications has been associated with various adverse effects, indicating a need
      for alternative approaches for the prevention and treatment of COPD. This study
      investigated the mechanism underlying the effects of trans-anethole in a mouse
      model of COPD induced by porcine pancreatic elastase (PPE) and lipopolysaccharide
      (LPS). BALB/c mice were orally administered trans-anethole (62.5, 125, 250, or
      500mg/kg) 2h before intranasal challenge with 1.2 units of PPE and 7MUg of LPS.
      Lactate dehydrogenase (LDH) activity, cell counts, lung histology, cytokine
      production, and blood pressure were analyzed. Trans-anethole reduced LDH activity
      and inflammatory cell counts, including macrophage, neutrophil, and lymphocyte
      counts. trans-anethole 125mg/kg restored the histopathological changes induced in
      mouse lungs by PPE and LPS. trans-anethole reduced the serum concentrations of
      pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha), as well as significantly reducing blood pressure during
      chronic inflammation. Trans-anethole ameliorated chronic lung inflammation in a
      mouse model of COPD by reducing the serum concentrations of pro-inflammatory
      cytokines such as TNF-alpha and IL-6, and by reducing blood pressure. The present
      results indicate that trans-anethole may be a potential therapeutic agent for
      prophylaxis and treatment in patients with chronic lung inflammation.

PMID- 28511345
TI  - ROS homeostasis, a key determinant in liver ischemic-preconditioning.
AB  - Reactive Oxygen Species (ROS) are key mediators of ischemia-reperfusion injury
      but also required for the induction of the stress response that limits tissue
      injury and underlies the protection provided by ischemic-preconditioning
      protocols. Liver steatosis is an important risk factor for liver transplant
      failure. Liver steatosis is associated with mitochondrial dysfunction and
      excessive mitochondrial ROS production. Studies aiming at decreasing the
      sensibility of the steatotic liver to ischemia-reperfusion injury using pre
      conditioning protocols, have shown that the steatotic liver has a reduced
      capacity to respond to these protocols. Recent studies indicate that these
      effects are related to a reduced capacity of the steatotic liver to respond to
      elevated ROS levels following reperfusion by inducing a compensatory response.
      This failure to respond to ROS is associated with reduced levels of antioxidants,
      mitochondrial damage, hepatocyte cell death, activation of the immune system and
      induction of pro-fibrotic mediators.

PMID- 28511349
TI  - Brown and black carbon in Beijing aerosol: Implications for the effects of brown
      coating on light absorption by black carbon.
AB  - Brown carbon (BrC) is increasingly included in climate models as an emerging
      category of particulate organic compounds that can absorb solar radiation
      efficiently at specific wavelengths. Water-soluble organic carbon (WSOC) has been
      commonly used as a surrogate for BrC; however, it only represents a limited
      fraction of total organic carbon (OC) mass, which could be as low as about 20% in
      urban atmosphere. Using methanol as the extraction solvent, up to approximately
      90% of the OC in Beijing aerosol was isolated and measured for absorption spectra
      over the ultraviolet-to-visible wavelength range. Compared to methanol-soluble OC
      (MSOC), WSOC underestimated BrC absorption by about 50% at 365nm. The mass
      absorption efficiencies measured for BrC in Beijing aerosol were converted to the
      imaginary refractive indices of BrC and subsequently used to compute BrC coating
      induced enhancement of light absorption (Eabs) by black carbon. Eabs attributed
      to lensing was reduced in the case of BrC coating relative to that caused by
      purely-scattering coating. However, this reduction was overwhelmed by the effect
      of BrC shell absorption, indicating that the overall effect of BrC coating was an
      increase in Eabs. Methanol extraction significantly reduced charring of OC during
      thermal-optical analysis, leading to a large increase in the measured elemental
      carbon (EC) mass and an apparent improvement in the consistency of EC
      measurements by different thermal-optical methods.

PMID- 28511348
TI  - Integrated flood hazard assessment based on spatial ordered weighted averaging
      method considering spatial heterogeneity of risk preference.
AB  - Flood is the most common natural hazard in the world and has caused serious loss
      of life and property. Assessment of flood prone areas is of great importance for
      watershed management and reduction of potential loss of life and property. In
      this study, a framework of multi-criteria analysis (MCA) incorporating geographic
      information system (GIS), fuzzy analytic hierarchy process (AHP) and spatial
      ordered weighted averaging (OWA) method was developed for flood hazard
      assessment. The factors associated with geographical, hydrological and flood
      resistant characteristics of the basin were selected as evaluation criteria. The
      relative importance of the criteria was estimated through fuzzy AHP method. The
      OWA method was utilized to analyze the effects of different risk attitudes of the
      decision maker on the assessment result. The spatial ordered weighted averaging
      method with spatially variable risk preference was implemented in the GIS
      environment to integrate the criteria. The advantage of the proposed method is
      that it has considered spatial heterogeneity in assigning risk preference in the
      decision-making process. The presented methodology has been applied to the area
      including Hanyang, Caidian and Hannan of Wuhan, China, where flood events occur
      frequently. The outcome of flood hazard distribution presents a tendency of high
      risk towards populated and developed areas, especially the northeast part of
      Hanyang city, which has suffered frequent floods in history. The result indicates
      where the enhancement projects should be carried out first under the condition of
      limited resources. Finally, sensitivity of the criteria weights was analyzed to
      measure the stability of results with respect to the variation of the criteria
      weights. The flood hazard assessment method presented in this paper is adaptable
      for hazard assessment of a similar basin, which is of great significance to
      establish counterplan to mitigate life and property losses.

PMID- 28511346
TI  - Potential therapeutic action of nitrite in sickle cell disease.
AB  - Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes
      under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated
      dehydration, and adhesivity of red blood cells. Increased red cell fragility
      results in hemolysis, which reduces nitric oxide (NO) bioavailability, and
      induces platelet activation and inflammation leading to adhesion of circulating
      blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has
      emerged as an attractive therapeutic agent that targets delivery of NO activity
      to areas of hypoxia through bioactivation by deoxygenated red blood cell
      hemoglobin. In this study, we demonstrate anti-platelet activity of nitrite at
      doses achievable through dietary interventions with comparison to similar doses
      with other NO donating agents. Unlike other NO donating agents, nitrite activity
      is shown to be potentiated in the presence of red blood cells in hypoxic
      conditions. We also show that nitrite reduces calcium associated loss of
      phospholipid asymmetry that is associated with increased red cell adhesion, and
      that red cell deformability is also improved. We show that nitrite inhibits red
      cell adhesion in a microfluidic flow-channel assay after endothelial cell
      activation. In further investigations, we show that leukocyte and platelet
      adhesion is blunted in nitrite-fed wild type mice compared to control after
      either lipopolysaccharide- or hemolysis-induced inflammation. Moreover, we
      demonstrate that nitrite treatment results in a reduction in adhesion of
      circulating blood cells and reduced red blood cell hemolysis in humanized
      transgenic sickle cell mice subjected to local hypoxia. These data suggest that
      nitrite is an effective anti-platelet and anti-adhesion agent that is activated
      by red blood cells, with enhanced potency under physiological hypoxia and in
      venous blood that may be useful therapeutically.

PMID- 28511350
TI  - On the applicability of a hybrid bioreactor operated with polymeric tubing for
      the biological treatment of saline wastewater.
AB  - Effective biological treatment of high salt content wastewater requires
      consideration of both salt and organic toxicity. This study treated a synthetic
      saline wastewater containing NaCl (100gL-1) and 2,4-dimethylphenol (1.2gL-1) with
      a hybrid system consisting of a biological reactor containing spiral-coiled
      polymeric tubing through which the mixed feed was pumped. The tubing wall was
      permeable to the organic contaminant, but not to the salt, which allowed transfer
      of the organic into the cell-containing bioreactor contents for degradation,
      while not exposing the cells to high salt concentrations. Different grades of
      DuPont Hytrel polymer were examined on the basis of organic affinity predictions
      and experimental partition and mass transfer tests. Hytrel G3548 tubing showed
      the highest permeability for 2,4-dimethylphenol while exerting an effective salt
      barrier, and was used to verify the feasibility of the proposed system. Very high
      organic removal (99% after just 5h of treatment) and effective biodegradation of
      the organic fraction of the wastewater (>90% at the end of the test) were
      observed. Complete salt separation from the microbial culture was also achieved.

PMID- 28511347
TI  - Mitochondrial complex I deactivation is related to superoxide production in acute
      hypoxia.
AB  - Mitochondria use oxygen as the final acceptor of the respiratory chain, but its
      incomplete reduction can also produce reactive oxygen species (ROS), especially
      superoxide. Acute hypoxia produces a superoxide burst in different cell types,
      but the triggering mechanism is still unknown. Herein, we show that complex I is
      involved in this superoxide burst under acute hypoxia in endothelial cells. We
      have also studied the possible mechanisms by which complex I could be involved in
      this burst, discarding reverse electron transport in complex I and the
      implication of PTEN-induced putative kinase 1 (PINK1). We show that complex I
      transition from the active to 'deactive' form is enhanced by acute hypoxia in
      endothelial cells and brain tissue, and we suggest that it can trigger ROS
      production through its Na+/H+ antiporter activity. These results highlight the
      role of complex I as a key actor in redox signalling in acute hypoxia.

PMID- 28511352
TI  - Emission inventory and environmental distribution of decabromodiphenyl ether in
      China.
AB  - Decabromodiphenyl ether (decaBDE) is a highly brominated flame retardant that
      recent studies have identified as a potential persistent organic pollutant. Large
      amounts of decaBDE have been consumed and released in the environment in China,
      while no emission inventory has been available until now. In this study, a
      substance flow analysis was applied to establish the emission inventory of
      decaBDE in China from 1982 (the first year of decaBDE production in China) until
      2013 based on activity data, transfer coefficients, and emission factors. The
      results show that the stock of decaBDE continually increased, reaching a peak of
      290,000tons in 2007. The annual processing capacity of decaBDE also increased,
      and the processing capacity in 2013 was 49,000tons. Historical accumulative
      emissions were estimated to be 313.3tons from 1982 to 2013, and the annual
      emissions peaked in 2003 at 27.5tons. On average, decaBDE processing was the
      major source (58.4%) of total emissions, followed by treatment, production, and
      usage processes. From 1982 to 2013, decaBDE was released mainly into water
      sources, accounting for 50.7% of the accumulative emissions. At the provincial
      level, Guangdong, Shandong, and Zhejiang provinces were the largest producers in
      China. Simulations produced by the level III fugacity model showed that the
      projected concentration was very consistent with the measured value. The stock of
      decaBDE in the soil and sediment phases accounted for 99.8% of the total stock,
      and the transfer among the four environmental phases occurred mainly at the
      atmosphere-soil interface.

PMID- 28511351
TI  - Effects of various fertilization regimes on abundance and activity of anaerobic
      ammonium oxidation bacteria in rice-wheat cropping systems in China.
AB  - Anaerobic ammonium oxidation (anammox) is an important process in many marine and
      paddy ecosystems. However, few studies have reported on the contribution to the
      nitrogen cycle of anammox and its dynamics in rice-wheat cropping systems with
      different fertilization regimes. Here, isotope tracing and molecular techniques
      were used to determine the potential rates of anammox and their association with
      bacterial abundance, diversity, and activity. Rice-wheat cropping systems at two
      sites in Jiangsu Province, China were selected and the treatments at each site
      were: 1) no fertilization (CK), 2) 100% chemical fertilization (CF), 3) pig
      manure compost plus 50% chemical fertilization (PMCF), and 4) straw plus 100%
      chemical fertilization (SRCF). The results revealed that anammox bacteria with
      high abundance were detected in both the wheat and rice seasons. The abundance of
      anammox in PMCF treatment was higher than that in SRCF treatment in both Changshu
      and Jintan. Moreover, the abundance of anammox bacteria in CF treatment was
      significantly higher than that in CK in Changshu. Analysis of anammox hydrazine
      synthase beta subunit (hzs-beta) gene sequences showed that in the rice season,
      the anammox bacteria Ca. Brocadia, Ca. Scalindua, and Ca. Jettenia were present.
      In contrast, all of the anammox hydrazine oxidase (hzo) genes were affiliated
      with Ca. Brocadia, suggesting that hzs genes are more representative of anammox
      biological diversity compared to hzo. Sequences from the PMCF treatment where
      affiliated with both Ca. Jettenia and Ca. Brocadia, and showed the highest
      diversity. Anammox activity was detected in both the wheat and rice seasons, but
      there were significant differences between seasons. The anammox rates were in the
      range 0.34 to 1.04nmol dinitrogen gas?g-1 dry soil?h-1, and 3.15 to 9.62% of
      dinitrogen gas emissions were attributed to anammox. However, no significant
      difference among the fertilizer treatments for anammox activity was found in the
      study.

PMID- 28511353
TI  - Assessment of water retention function as tool to improve integrated watershed
      management (case study of Poprad river basin, Slovakia).
AB  - The presented study concentrates on assessing the ecosystem function of water
      retention. The water retention function is defined as the ability of the
      landscape to retain water, slow runoff and encourage water infiltration. The
      water retention function was expressed by calculating the hydric significance
      (HS) indicator. This method is based on scoring the individual input parameters
      according to their overall impact on watershed hydrology. The study was conducted
      on a sample area of Poprad River basin. The final results presented a spatial
      distribution of hydric function within the watershed classified according to its
      significance into four classes (from limited to excellent significance). A
      breakdown of the results on the level of elementary watersheds was used in order
      to examine those with low hydric function. The results showed a significant
      influence of land-use on retention function; however, this impact could be
      limited by extreme precipitation or high soil water saturation. The methodology
      of hydric significance represents an innovative approach towards assessment of
      ecosystem function of water retention on regional level.

PMID- 28511354
TI  - Occurrence, distribution and sources of bisphenol analogues in a shallow Chinese
      freshwater lake (Taihu Lake): Implications for ecological and human health risk.
AB  - Since the production and use of BPA were regulated in China around 2008, several
      bisphenol analogues were widely used to substitute BPA in the manufacture of
      polycarbonates, epoxy resins, and plastics. However, there is limited
      understanding of the spatial distribution, potential sources and risk assessment
      for those bisphenol analogues. In this study, seven bisphenol analogues were
      investigated in water and sediment samples from Taihu Lake, China. Compared to
      the same lake in 2013 (range: 5.4-87ng/L for waters and 0.37-8.3ng/g dw for
      sediments), the samples from Taihu Lake contained comparatively higher BPs
      (2.0*102-9.5*102ng/L and 23-4.3*102ng/gdw) in 2016, indicating that the BPs
      levels in Taihu Lake have aggravated recently. In waters, BPAF has become the
      predominant congener in Taihu Lake, suggesting that BPAF was the most widely used
      substitute of BPA, recently. In sediments, BPA was the most abundant compound.
      Moderate or strong correlations between some individual BPs indicated that those
      BPs may have the common sources and/or similar environmental behavior. The
      strongly positive correlation between ?BPs and TOC content indicated that TOC
      content was one of the major factors controlled the distribution of ?BPs in the
      sediment. The risk assessment at the sampling sites showed no high eco-toxicity
      or estrogenic risk in Taihu Lake.

PMID- 28511355
TI  - Identification of polar transformation products and high molecular weight
      polycyclic aromatic hydrocarbons (PAHs) in contaminated soil following
      bioremediation.
AB  - Bioremediation is a technique commonly used to reduce the toxicity associated
      with polycyclic aromatic hydrocarbons (PAHs) in contaminated soils. However, the
      efficacy of bioremedial applications is evaluated based on the removal of a
      subset of parent (or unsubstituted) PAHs and does not incorporate toxic polar
      transformation products or the more mutagenic high molecular weight PAHs
      (MW>=302amu or MW302-PAHs). Previously, an effects-directed analysis approach was
      used to assess the effect of bioremediation on the toxicity of a coal tar
      contaminated soil. Increased genotoxicity and developmental toxicity was measured
      postbioremedation in the more polar soil extract fractions, as compared to the
      less polar fractions where the targeted PAHs eluted, and could not be attributed
      to the 88 target PAHs analyzed for (including selected oxygen-containing PAHs).
      In this study, comprehensive two-dimensional gas chromatography time-of-flight
      and liquid chromatography quadrupole time-of-flight mass spectrometry were used
      to characterize transformation products in the soil extract fractions identified
      as toxic, previously. Additionally, the degradation of 12MW302-PAHs, picene
      (MW=278) and coronene (MW=300) were evaluated following bioremediation. Non
      targeted analysis resulted in the tentative identification of 10 peaks with
      increased intensity postbioremediation (based on mass spectral library matching
      and fragmentation patterns from >5000 candidate peaks in the soil extracts).
      Several of these compounds contained oxygen, suggesting they would be relatively
      polar. MW302-PAHs were not significantly degraded during bioremediation,
      suggesting that the carcinogenic potential associated with these PAHs might
      remain unchanged. The results of this study suggest that polar transformation
      products, and MW302-PAHs, should be considered for realistic risk assessment of
      bioremediated soils.

PMID- 28511356
TI  - Effects of sewage effluents and seasonal changes on the metabolism of three
      Atlantic rivers.
AB  - Sewage inputs on fluvial ecosystems affect benthic communities and alter trophic
      networks resulting in changes on river functioning. Functional indicators (e.g.
      river metabolism) have been proposed as a valuable tool to evaluate ecosystem
      impairment. In the present study we monitored river metabolism in spring (few
      days after a major flood) and in summer (after 35days of low flow conditions)
      using both single-station and two-stations methods over a 24h period up and
      downstream of wastewater treatment plant (WWTP) effluents on three Atlantic river
      reaches located in northern Spain (Europe). Concurrently with river metabolism,
      we characterized environmental characteristics (flow, velocity, depth, pH, water
      temperature, nutrients, etc.), benthic macroinvertebrate communities and biofilm
      (algae and epilithic biomass). Ecosystem Respiration (ER24) was similar at the
      different periods and locations, but Gross Primary Productivity (GPP) tended to
      decrease in impacted reaches (downstream WWTPs) and in summer (except in the Saja
      River). However, the balance of the metabolic processes showed a trend towards
      autotrophy in the largest river, while WWTP effluents increased its autotrophy.
      Chlorophyll a concentration was >4 times larger in spring than in summer in all
      river reaches, while epilithic biomass followed a similar but less obvious
      pattern. Increase of invertebrate scraper densities (mainly, Potamopyrgus
      antipodarum) seems to be a plausible explanation for biofilm biomass temporal
      patterns in all sites (higher in spring than in summer), altering GPP and ER24
      patterns. Thus, metabolism rates show different responses to WWTP effluents
      depending on season and on the relationships among functional and structural
      components, with special focus on the composition and structure of
      macroinvertebrate communities. Increasing our understanding of cause-effect
      relationships on the impairment of aquatic ecosystems needs to account for both
      structural and functional components and their interactions.

PMID- 28511358
TI  - The degree of phosphorus saturation of agricultural soils in Germany: Current and
      future risk of diffuse P loss and implications for soil P management in Europe.
AB  - Decades of intensive agricultural production with excessive application of P
      fertilizer have resulted in the accumulation of P in soils, threatening water
      bodies in most industrialized countries with eutrophication. In our study, we
      elucidated the risk of P loss of German agricultural soils by transforming
      provided monitoring data of plant-available P determined by the calcium-acetate
      lactate (PCAL) and double-lactate method (PDL) into the degree of phosphorus
      saturation (DPS). As water-soluble phosphorus (WSP) is correlated to DPS, we
      derived a pedotransfer function (PTF) between PCAL and WSP for different soil
      types. Considering all soils together resulted in WSP=0.1918*PCAL (R2=0.80,
      n=54). Subsequently, risk parameters DPS and EPC0 were calculated from PCAL and
      PDL monitoring data (n>337,000) by using the determined PTF and soil type
      independent correlations with WSP, as published in an earlier study. Calculated
      DPS values from monitoring data indicated high risks of dissolved P loss for >76%
      of German arable soils. Recent suggestions by the Association of German
      Agricultural Analytical and Research Institutes (VDLUFA) to reduce recommended
      PCAL levels are crucial for the reduction of P loss risks in the future. The
      accuracy of predicted DPS and EPC0 values by CAL and other methods used in Europe
      to estimate plant-available P is limited by the soil type-dependency of these
      methods. Consequently, we recommend considering WSP as an agri-environmental soil
      P test across Europe. Our results indicate that a WSP level in soils can be
      defined that constitutes a reasonable compromise between the securing of
      agronomic production and the fulfillment of environmental goals.

PMID- 28511357
TI  - Establishing and testing a catchment water footprint framework to inform
      sustainable irrigation water use for an aquifer under stress.
AB  - Future water scarcities in the face of an increasing population, climate change
      and the unsustainable use of aquifers will present major challenges to global
      food production. The ability of water footprints (WFs) to inform water resource
      management at catchment-scale was investigated on the Steenkoppies Aquifer, South
      Africa. Yields based on cropping areas were multiplied with season-specific WFs
      for each crop to determine blue and green water consumption by agriculture.
      Precipitation and evapotranspiration of natural vegetation and other uses of blue
      water were included with the agricultural WFs to compare water availability and
      consumption in a catchment sustainability assessment. This information was used
      to derive a water balance and develop a catchment WF framework that gave
      important insights into the hydrology of the aquifer through a simplified method.
      This method, which requires the monitoring of only a few key variables, including
      rainfall, agricultural production, WFs of natural vegetation and other blue water
      flows, can be applied to inform the sustainability of catchment scale water use
      (as opposed to more complex hydrological studies). Results indicate that current
      irrigation on the Steenkoppies Aquifer is unsustainable. This is confirmed by
      declining groundwater levels, and suggests that there should be no further
      expansion of irrigated agriculture on the Steenkoppies Aquifer. Discrepancies
      between in- and outflows of water in the catchment indicated that further
      development of the WF approach is required to improve understanding of the
      geohydrology of the aquifer and to set and meet sustainability targets for the
      aquifer. It is envisaged that this 'working' framework can be applied to other
      water-stressed aquifers around the world.

PMID- 28511359
TI  - Occurrence of chemical contaminants in peri-urban agricultural irrigation waters
      and assessment of their phytotoxicity and crop productivity.
AB  - Water scarcity and water pollution have increased the pressure on water resources
      worldwide. This pressure is particularly important in highly populated areas
      where water demand exceeds the available natural resources. In this regard, water
      reuse has emerged as an excellent water source alternative for peri-urban
      agriculture. Nevertheless, it must cope with the occurrence of chemical
      contaminants, ranging from trace elements (TEs) to organic microcontaminants. In
      this study, chemical contaminants (i.e., 15 TEs, 34 contaminants of emerging
      concern (CECs)), bulk parameters, and nutrients from irrigation waters and crop
      productivity (Lycopersicon esculentum Mill. cv. Bodar and Lactuca sativa L. cv.
      Batavia) were seasonally surveyed in 4 farm plots in the peri-urban area of the
      city of Barcelona. A pristine site, where rain-groundwater is used for
      irrigation, was selected for background concentrations. The average concentration
      levels of TEs and CECs in the irrigation water impacted by treated wastewater
      (TWW) were 3 (35+/-75MUgL-1) and 13 (553+/-1050ngL-1) times higher than at the
      pristine site respectively. Principal component analysis was used to classify the
      irrigation waters by chemical composition. To assess the impact of the occurrence
      of these contaminants on agriculture, a seed germination assay (Lactuca sativa L)
      and real field-scale study of crop productivity (i.e., lettuce and tomato) were
      used. Although irrigation waters from the peri-urban area exhibited a higher
      frequency of detection and concentration of the assessed chemical contaminants
      than those of the pristine site (P1), no significant differences were found in
      seed phytotoxicity or crop productivity. In fact, the crops impacted by TWW
      showed higher productivity than the other farm plots studied, which was
      associated with the higher nutrient availability for plants.

PMID- 28511360
TI  - Refined 2013-based vehicle emission inventory and its spatial and temporal
      characteristics in Zhengzhou, China.
AB  - Vehicle emission is becoming one of the most important pollution sources because
      of the increase in vehicle population and activity in China. A more reasonable
      and complete vehicle emission inventory in Zhengzhou for the year 2013 was
      developed in this study. This inventory is suitable for local emission factors
      and vehicle kilometers of travel. Estimates show that the total carbon monoxide
      (CO), hydrocarbon (HC), nitrogen oxide (NOX), particulate matter (PM2.5 and PM10)
      and sulfur dioxide (SO2) emissions were 291Gg, 35Gg, 106Gg, 6Gg, 7Gg, and 3Gg,
      respectively. Approximately 55% of CO and HC emissions were from light duty
      gasoline vehicles and normal gasoline motorcycles, whereas approximately 60% of
      NOX, PM2.5, PM10 and SO2 were from heavy duty diesel vehicles, heavy duty diesel
      trucks, and medium duty diesel trucks. The spatial distribution of emissions was
      allocated in grid cells based on a road network and traffic flows with a
      resolution of 1km*1km at different road types and locations, which shows that the
      six aforementioned air pollutants have similar characteristics in administrative
      districts. Emissions are mainly concentrated on the central grid cells of each
      part and in good agreement with line sources. The spatial characteristics were
      compared at a resolution of 3km*3km and in a population-based approach. The
      network approach yields better level estimates in this study. Meanwhile, the
      preliminary temporal profiles were also established for on-road mobile source.

PMID- 28511361
TI  - Predicting phosphorus availability from chemically diverse conventional and
      recycling fertilizers.
AB  - Fertilizers produced from heterogeneous, phosphorus-rich biowastes are becoming
      increasingly relevant. Treatment and processing (combustion, pyrolysis, anaerobic
      digestion, etc.) increase the diversity of their physico-chemical composition
      even further. We investigated several approaches to characterize P availability
      from a set of 13 contrasting fertilizers. We tested them directly using standard
      fertilizer extractions, as well as a continuous, sink-based P extraction (iron
      bag) method. We also performed Olsen, CAL and diffusive gradients in thin films
      (DGT) tests on fertilized soil. Standard extractions correlated only weakly,
      whereas the iron bag method correlated highly (0.73<R2<0.85) with plant P uptake.
      Among the tests conducted on fertilized soils, DGT was equivalent or slightly
      better than Olsen, showing R2s of about 0.90 for P uptake and plant growth. Our
      results suggest that the validity of standard P fertilizer tests needs to be
      reassessed in the context of increasingly diverse recycling fertilizers.

PMID- 28511362
TI  - Towards complete and harmonized assessment of soil carbon stocks and balance in
      forests: The ability of the Yasso07 model across a wide gradient of climatic and
      forest conditions in Europe.
AB  - Accurate carbon-balance accounting in forest soils is necessary for the
      development of climate change policy. However, changes in soil organic carbon
      (SOC) occur slowly and these changes may not be captured through repeated soil
      inventories. Simulation models may be used as alternatives to SOC measurement.
      The Yasso07 model presents a suitable alternative because most of the data
      required for the application are readily available in countries with common
      forest surveys. In this study, we test the suitability of Yasso07 for simulating
      SOC stocks and stock changes in a variety of European forests affected by
      different climatic, land use and forest management conditions and we address
      country-specific cases with differing resources and data availability. The
      simulated SOC stocks differed only slightly from measured data, providing
      realistic, reasonable mean SOC estimations per region or forest type. The change
      in the soil carbon pool over time, which is the target parameter for SOC
      reporting, was generally found to be plausible although not in the case of
      Mediterranean forest soils. As expected under stable forest management
      conditions, both land cover and climate play major roles in determining the SOC
      stock in forest soils. Greater mean SOC stocks were observed in northern
      latitudes (or at higher altitude) than in southern latitudes (or plains) and
      conifer forests were found to store a notably higher amount of SOC than broadleaf
      forests. Furthermore, as regards change in SOC, an inter-annual sink effect was
      identified for most of the European forest types studied. Our findings
      corroborate the suitability of Yasso07 to assess the impact of forest management
      and land use change on the SOC balance of forests soils, as well as to accurately
      simulate SOC in dead organic matter (DOM) and mineral soil pools separately. The
      obstacles encountered when applying the Yasso07 model reflect a lack of available
      input data. Future research should focus on improving our knowledge of C inputs
      from compartments such as shrubs, herbs, coarse woody debris and fine roots. This
      should include turnover rates and quality of the litter in all forest
      compartments from a wider variety of tree species and sites. Despite the
      limitations identified, the SOC balance estimations provided by the Yasso07 model
      are sufficiently complete, accurate and transparent to make it suitable for
      reporting purposes such as those required under the UNFCCC (United Nations
      Framework Convention on Climate Change) and KP (Kyoto Protocol) for a wide range
      of forest conditions in Europe.

PMID- 28511363
TI  - Solving the Mystery of the Antero Lateral Ligament.
AB  - INTRODUCTION: The cruciate ligaments are essential for the antero-posterior
      stability of the knee joint. In Anterior Cruciate Ligament (ACL) rupture, though
      reconstructive surgery is a widely accepted and proven procedure, there is still
      an unacceptably high re-injury rate. The fact that the rotational instability
      persists even after the surgical reconstruction of ACL injury has evoked a new
      interest in the study of the soft tissue structures on the anterolateral aspect
      of the knee joint. The stability of the knee joint was found to improve
      dramatically if ACL reconstruction is accompanied with the reconstruction of the
      anterolateral soft structures of the knee. AIM: To identify the attachment and
      observe the measurable parameters of Antero Lateral Ligament (ALL) and its
      relationship with the adjacent bony landmarks. MATERIALS AND METHODS: Twenty six
      cadaveric specimens of knee joints were collected from the Department of Anatomy,
      Amrita School of Medicine, Amrita Institute of Medical Sciences, Kochi and were
      dissected for the anterolateral ligament. Various parameters of ALL in extended
      knee- the length, width at midpoint and at the femoral-tibial attachments and
      thickness- were measured. The relationship of femoral attachment of ALL with the
      lateral femoral epicondyle as well as the tibial attachment with the Gerdy's
      Tubercle (GT) and head of fibula were also noted. RESULTS: ALL was identified in
      all the 26 cadaveric knee specimens. It was 39.2+/-7.2 mm in length, 6.5+/-2.7 mm
      in width at femoral attachment and 7.4+/-3.4 mm at tibial attachment, while the
      thickness was 1.0+/-0.5 mm. At the femoral attachment it was 7.1+/-3.4 mm
      proximal to and 4.0+/-2.9 mm posterior to the lateral epicondyle while at the
      distal attachment it was 20.4+/-3.1 mm posterior to the GT and 21.33+/-4.6 mm
      anterior to the head of the fibula. CONCLUSION: The ALL was found to be a
      distinct, supporting anatomical structure on the anterolateral aspect of the
      human knee. There is a high incidence of ALL lesions in ACL injuries which causes
      high-grade pivot-shift. The reconstruction of ALL along with that of ACL could
      lead to a decrease in the re-injury rates. The anatomical descriptions and the
      morphometry of ALL may be of great value to the orthopaedic surgeons in
      performing a more effective reconstructive surgery of ACL.

PMID- 28511364
TI  - Comparative Study on Insall-Salvati Index by Radiological and Clinical Methods in
      a Tertiary Care Centre of North Bengal, India.
AB  - INTRODUCTION: Patellar height is an important parameter of patellar stability.
      Its importance is evident from various attempts to measure it, by different
      scientists from time to time and many indices have been derived among which
      Insall-Salvati index (IS index) is the most simple, accurate and easy to measure.
      In this study a new clinical method has been tried to measure patellar height by
      applying the same principle of IS index. AIM: To compare clinical method of
      measurement of IS index with the one derived radiologically and to establish the
      higher cut off value of the clinical method. MATERIALS AND METHODS: In the
      present study 186 knee joints (93 subjects) were subjected to measurement of
      patellar height by both clinical and radiological methods. The IS index was
      measured bilaterally from lateral view of X-ray plates and it was measured
      clinically in every knee joint. Both the values were compared using students t
      test and higher cut off values were set for normal knee joint for the clinical
      method. RESULTS: Among 93 study participants majority were females (54.83%), age
      of the patients varied from 10-68 years with mean age of 28 years and Standard
      deviation (SD) of 16.4. It was found that, there was no statistically significant
      difference between the mean values obtained by clinical method of measurement,
      compared to conventional one (IS Index) for both the genders and age groups on
      both the sides. A cut off value of 0.98 cm by clinical method gives sensitivity
      of 80% and specificity of 36% with area under the ROC curve 0.596. CONCLUSION:
      The subjects with patellar height of less than cut off value by clinical method
      can avoid radiological investigation as there was no statistically significant
      difference of IS index between radiological and clinical methods.

PMID- 28511365
TI  - Morphological and Morphometric Analysis of Hypoglossal Canal in North Indian Dry
      Skulls and It's Significance in Cranial Base Surgeries.
AB  - INTRODUCTION: Hypoglossal Canal (HC) is a paired bony passage which is situated
      above the Occipital Condyle (OC) and transmits hypoglossal nerve and blood
      vessels. Studies on the osteotic variations of HC has been a field of
      considerable interest to research workers especially because of its clinical,
      radiological and surgical significance. AIM: The aim of the present study was to
      analyze the morphological and morphometric features of HC and its topographical
      relationship with OC. MATERIALS AND METHODS: The present study was done on 50
      human dry skulls. The HC was looked for presence of spur and septa along with its
      location in the canal and were classified into different types accordingly. The
      distance of extracranial and intracranial openings of HC from the posterior end
      of OC was measured by Sliding Vernier caliper. Angle of inclination of HC with
      the midsagittal plane was measured with the help of goniometer. RESULTS: In the
      present study, we observed osteotic variations in the HC in 52% skulls. The spur
      (Type 2) was seen in 28% and incomplete septa (Type 3) was noted in 26% skulls.
      In some cases, spur and septa were seen in different locations of same HC.
      However, complete septa (Type 4) were not observed in our study. Spur and septa,
      both were present more frequently on the left side. The external and internal
      distance of HC from posterior end of OC was more on the left side in comparison
      to the right side. The anterior angle of HC to the midsagittal plane is less in
      comparison to posterior angle in case of double internal opening of HC.
      CONCLUSION: The present study regarding morphologic and morphometric analysis of
      HC and its relation to the OC will provide important information in North Indian
      population. It will enable effective and reliable surgical intervention in the
      area of HC and craniovertebral junction leading to better postoperative outcome.

PMID- 28511366
TI  - Gender Linked Metric Analysis of Portal Vein: A Sonographic Appraisal.
AB  - INTRODUCTION: Portal hypertension is one of the most mystifying and disconcerting
      abdominal ailment. Ultrasonography (USG) is an effective diagnostic tool for its
      prompt management. Knowledge of normal calibre of portal vein in a local setting
      is essential as literature reports contrasting values in different regions. It
      helps in early diagnosis of portal hypertension even before it is clinically
      manifested thereby assisting clinicians and interventional radiologists in
      pertinent management. AIM: Study was aimed to evaluate the Portal Vein Diameter
      (PVD) and find its correlation with gender by using USG in North Indian
      population. MATERIALS AND METHODS: A total of 300 healthy adults were included in
      the study. Portal vein diameter was measured in supine position and normal
      respiration by grey scale USG. The portal vein diameter was correlated with age
      and gender statistically using independent Student's t-test and ANOVA. RESULTS:
      Mean PVD of (9.49+/-1.03 mm) was observed in the present cross-sectional study.
      Male showed a significantly higher mean PVD (9.70+/-1.02 mm) as compared to
      females (9.10+/-0.94 mm). CONCLUSION: Scarcity of information concerning
      ultrasonographically measured standard portal vein diameter and inconstant values
      reported in literature necessitates the need for establishing local standard
      value. In the given subset of population the portal vein diameter was influenced
      by the gender. The information will be helpful in prompt diagnosis and management
      of portal hypertension.

PMID- 28511367
TI  - Neurobehavioural Changes in a Hemiparkinsonian Rat Model Induced by Rotenone.
AB  - INTRODUCTION: Rotenone, a mitochondrial complex I inhibitor is used as a
      neurotoxin agent to reproduce the neuropathological, and behavioural feature of
      Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone
      with various doses through different routes of administration, mortality is being
      reported. Low dose takes a longer duration to produce PD symptoms in animals.
      This present study was designed to create hemiparkinsonian 'partial' lesion model
      by rotenone at a single moderate dose in two sites of striatum in albino rats and
      also to assess its toxicity by behavioural parameters and by microscopic study.
      AIM: To assess all the motor deficits in lesioned animals that are due to the
      depletion of dopaminergic neurons or its terminals, the lesioned animals were
      administered with anti-parkinsonian drug, Levodopa which should counteract motor
      deficits in rats. MATERIALS AND METHODS: The unilateral partially lesioned PD
      model was induced by rotenone stereotaxically into two sites of striatum of male
      Wistar albino rats at a dosage of 25 MUg of rotenone/site. Rats were tested for
      its neurobehavioural activity on 7th day, 14th day, 21st day and on 30th day
      after rotenone infusion and compared with the sham group and sacrificed on 21st
      and 30th day for microscopic studies. L-DOPA was administered from 21st day to
      30th day after lesion and compared with the lesioned group for the motor
      performance and sacrificed on 30th day for histology. Statistical analysis using
      One-way Analysis of variance followed by Tukey's test was applied for behavioural
      studies. RESULTS: Statistical analysis showed that the signs and symptoms like
      motor in-coordination and postural disturbances are highly significant (p<0.05)
      on 14th and 21st day after administration of rotenone when compared to sham
      group. In L-DOPA treated rats, all the motor deficits were reversed. The neuronal
      cell death was minimal and sprouting of nerve terminals was detected. In lesioned
      group, the degeneration of nerve terminals and striatal neurons were in
      progressive manner. CONCLUSION: These findings suggest that intrastriatal
      infusion of rotenone at a moderate dose could be used for producing
      hemiparkinsonian partially lesioned animal model without any mortality. Hence,
      this model is suitable for evaluating behavioural studies and in drug screening
      programs even for a long term study.

PMID- 28511368
TI  - Evaluation of CYP1B1 Expression, Oxidative Stress and Phase 2 Detoxification
      Enzyme Status in Oral Squamous Cell Carcinoma Patients.
AB  - INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) affects global health with
      increasing incidence and mortality rate. It may involve exposure to carcinogens
      from tobacco smoking or chewing. Alteration in expression of gene encoding the
      enzymes concerned with carcinogen biotransformation along with oxidative stress
      may increase or decrease the risk of cancer. AIM: To evaluate the expression of
      CYP1B1 gene in OSCC patients along with its relation with oxidative stress and
      phase 2 detoxification enzyme status. MATERIALS AND METHODS: In the present
      study, CYP1B1 genotypic analysis was carried out along with estimation of serum
      Total Antioxidant Activity (TAA), erythrocyte Malondialdehyde (MDA) levels and
      serum Glutathione-S-Transferase (GST) activity in 20 OSCC patients and
      statistically compared with that of age matched 20 healthy subjects, served as
      control by using student's t-test. RESULTS: It was observed that 85% of
      histopathologically diagnosed OSCC patients had CYP1B1 expression with
      significantly elevated levels of MDA (p<0.001). In addition, plasma total
      antioxidant status and serum GST levels were decreased significantly (p<0.05) in
      OSCC patients as compared to the healthy controls to overcome the burden of
      oxidative stress. CONCLUSION: On the basis of the present study, we conclude that
      the expression of CYP1B1 is an important determinant of carcinogenesis and
      significantly associated with oxidative stress characterized by decreased serum
      GST and total antioxidant levels in OSCC patients.

PMID- 28511369
TI  - Study of Nitrosative Stress in 'Pregnancy Induced Hypertension'.
AB  - INTRODUCTION: Hypertension is the most common medical problem encountered during
      pregnancy. Pregnancy Induced Hypertension (PIH) is also called a disease of
      maternal endothelium. Nitric-oxide being a potent vasodilator released by
      endothelial cells, its role has been implicated in PIH. AIM: To study the role of
      reactive nitrogen species in PIH. MATERIALS AND METHODS: One hundred and twenty
      samples were selected for the study. Of these, 60 patients had PIH (case) and the
      rest without PIH (control). Estimation of serum nitric- oxide, serum nitrothiol,
      serum total thiol was done. RESULTS: The study showed decreased NOx (Mono
      nitrogen oxide No and No2) levels in PIH as compared to control (p< 0.001). PIH
      patients had significantly higher levels of S-nitrothiols than control (p<0.01).
      Thiol levels were decreased in PIH as compared to control (p<0.001). CONCLUSION:
      Thus, it is concluded from this study that nitrosative stress represents a point
      of convergence for several contributing factors potentially leading to the
      clinical manifestations of pregnancy induced hypertension. The antioxidants are
      used up while scavenging the free radicals.

PMID- 28511370
TI  - Correlation of Plasma Neutrophil Elastase Activity and Endogenous Protease
      Inhibitor Levels with the Severity of Pre-eclampsia.
AB  - INTRODUCTION: Pre-eclampsia (PE) is a common maternal syndrome characterized by
      severe systemic inflammatory response including neutrophil activation leading to
      uncontrolled activity of elastase. The excessive activity of elastase would lead
      to destroyal of the integrity of endothelial cells and could exacerbate the
      pathophysiological symptoms in PE. Thus, assessment of NE activity and its
      control mechanisms would be of relevance in the determination of severity of PE.
      AIM: To correlate the activity of plasma NE and its endogenous inhibitors alpha1
      antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG) with severity of PE.
      MATERIALS AND METHODS: A comparative study was conducted between normotensive
      pregnant (n=50) and pre-eclamptic (n=50) women. Serum C-Reactive Protein (CRP)
      was estimated by rapid latex slide and uric acid by uricase method. Plasma
      elastase was estimated using succinyl tri- L-alanyl-p-nitroanilide as substrate.
      Plasma alpha1-AT, alpha2-MG and NE- alpha1-AT complex were quantified by ELISA.
      ANOVA and Pearson's correlation tests were used to analyze the data. The results
      were expressed as mean+/-SD and p-value <0.001 was considered statistically
      highly significant. RESULTS: The activity of elastase was increased significantly
      in severe PE (0.62+/-0.08) in comparison to normal (0.35+/-0.10) and mild pre
      eclamptic subjects (0.37+/-0.03). The values of alpha1-AT were significantly less
      in mild (83.94+/-25.08) and severe PE (68.58+26.39) in comparison to normal
      (110.26+/-42.39). There was a significant rise in the levels of alpha2-MG in
      severe PE. However, the complex estimation did not evince any significant
      changes. CONCLUSION: The results of the present study indicate a significantly
      elevated elastase activity, alpha2-MG levels and decreased alpha1-AT in severe PE
      patients. The correlation analyses of PE severity parameters with NE, alpha1-AT
      and alpha2-MG further support the roles of these molecules in the assessment of
      severity of PE.

PMID- 28511371
TI  - Study of Serum Total PSA and Free PSA as an Oncological Marker in Breast Tumour.
AB  - INTRODUCTION: Breast Cancer (BC) cases are rising alarmingly all over the world
      and India is not an exception. This rising trend is due to an increased age at
      first child birth, decreased breast feeding, and the changing lifestyle mostly in
      urban India. With the advent of more sensitive methodologies and research works
      in this field, it has been suggested that Prostate Specific Antigen (PSA) plays
      an important role in the pathogenesis of breast cancer besides other established
      tumour markers. AIM: To study the molecular forms of PSA-total and free PSA in
      benign and malignant tumours and to analyse their association with the tumour
      burden. MATERIALS AND METHODS: The present study was conducted in collaboration
      with Gauhati Medical College and Hospital and Dr B Borooah Cancer Institute,
      Guwahati, Assam, India. Women in the age group of 18-65 years with recently
      diagnosed tumour (benign/malignant) in the breast were included in the study.
      Women taking Oral Contraceptive Pill (OCP), hormone replacement therapy, with
      past/present history of gynaecological/other malignancy and chronic endocrine
      disease like diabetes, thyroid disorders were excluded. The case group comprised
      of 50 female subjects with newly diagnosed Benign Breast Disease (BBD) and 50
      subjects with BC, while 50 age matched healthy females without any signs and
      symptoms of breast discomfort were included in the control group. Laboratory
      tests done were Serum Total PSA (TPSA), Free PSA (FPSA), Fasting Blood Glucose
      (FBS), serum urea, serum creatinine and fasting lipid profile. TPSA and FPSA was
      measured again in both the test groups after 10-14 days of surgery/therapy.
      RESULTS: A fall in postoperative value of total and free PSA in BC case group was
      noticed. In Grade I tumours the mean value of total PSA (1.813 ng/ml) and free
      PSA (1.149 ng/ml) were higher than those with Grade III tumours (TPSA-1.07 ng/ml
      and FPSA-1.002 ng/ml). Mean value of Fasting Blood Sugar (FBG), total cholesterol
      and Low Density Lipoprotein (LDL) in BC case group was higher than the control
      group. CONCLUSION: From the study, we can conclude PSA as a possible new marker
      for diagnosis and prognosis of BC.

PMID- 28511372
TI  - Comparison of Methods to Assay Liver Glycogen Fractions: The Effects of
      Starvation.
AB  - INTRODUCTION: There are several methods to extract and measure glycogen in animal
      tissues. Glycogen is extracted with or without homogenization by using cold
      Perchloric Acid (PCA). AIM: Three procedures were compared to determine glycogen
      fractions in rat liver at different physiological states. MATERIALS AND METHODS:
      The present study was conducted on two groups of rats, one group of five rats
      were fed standard rodent laboratory food and were marked as controls, and another
      five rats were starved overnight (15 hour) as cases. The glycogen fractions were
      extracted and measured by using three methods: classical homogenization, total
      glycogen-fractionation and homogenization-free protocols. RESULTS: The data of
      homogenization methods showed that following 15 hour starvation, total glycogen
      decreased (36.4+/-1.9 vs. 27.7+/-2.5, p=0.01) and the change occurred entirely in
      Acid Soluble Glycogen (ASG) (32.0+/-1.1 vs. 22.7+/-2.5, p=0.01), while Acid
      Insoluble Glycogen (AIG) did not change significantly (4.9+/-0.9 vs. 4.6+/-0.3,
      p=0.7). Similar results were achieved by using the method of total-glycogen
      fractionation. Homogenization-free procedure indicated that ASG and AIG fractions
      compromise about 2/3 and 1/3 of total glycogen and the changes occurred in both
      ASG (24.4+/-2.6 vs. 16.7+/-0.4, p<0.05) and AIG fraction (8.7+/-0.8 vs. 7.1+/
      0.3, p=0.05). CONCLUSION: The findings of 'homogenization assay method' indicate
      that ASG is the major portion of liver glycogen and is more metabolically active
      form. The same results were obtained by using 'total-glycogen-fractionation
      method'. 'Homogenization-free method' gave different results, because AIG has
      been contaminated with ASG fraction. In both 'homogenization' and 'homogenization
      free' methods ASG must be extracted at least twice to prevent contamination of
      AIG with ASG.

PMID- 28511373
TI  - Prevalence of Nutritional Deficiency Anaemia and Its Impact on Scholastic
      Performance among Undergraduate Medical Students.
AB  - INTRODUCTION: Nutritional deficiency anaemia can lead to development of headache,
      fatigue, lethargy, apathy, exertional dyspnoea, palpitations and tinnitus and
      thereby decrease the quality of everyday life to a great extent. Such symptoms
      may pose a hindrance for students in their academic life and have a negative
      impact on their career. AIM: To determine prevalence of nutritional deficiency
      anaemia and its correlation with academic performance among medical students.
      MATERIALS AND METHODS: A cross-sectional study was conducted at Adichunchanagiri
      Institute of Medical Sciences. Two hundred eighty nine healthy undergraduate
      medical students of both genders were included in this study. A predesigned and
      pre-structured questionnaire was used as a tool to obtain information regarding
      demographic profile, dietary habits and academic performance. Haemoglobin level
      was estimated. Student's t-test and Chi-square test were employed. RESULTS:
      Majority of the participants were within the age group of 17-20 years (84.4%).
      The overall prevalence of anaemia was 15.6% with high rates among female students
      (93.3%), this gender difference was statistically significant (p<0.001). There
      was statistically significant difference in Hb% (p=0.009) among high and low
      performers. There was no association between the anaemic status and students
      scholastic performance (chi2=3.1533, p=0.368). CONCLUSION: The mean haemoglobin
      level was higher among low performer, indicating that nutritional anaemia may not
      ?play a major role in educational performance and intelligence in higher
      education.

PMID- 28511374
TI  - Assessment of Lipid Peroxidation and Antioxidant Status in Vanillic Acid Treated
      7,12-Dimethylbenz[a]anthracene Induced Hamster Buccal Pouch Carcinogenesis.
AB  - INTRODUCTION: Vanillic acid, a naturally occurring bioactive substance, possesses
      diverse pharmacological potential including free radical scavenging and
      anticancer properties. Excessive generation of Reactive Oxygen Species (ROS) and
      insufficient antioxidant potential has been involved in numerous pathological
      disorders, including cancer. AIM: To explore the anti-lipid peroxidative and
      antioxidant efficacy of vanillic acid in Dimethylbenz[a]Anthracene (DMBA) induced
      oral carcinogenesis. MATERIALS AND METHODS: Topical application of DMBA for 14
      weeks in the buccal pouch of hamsters resulted in well developed oral squamous
      cell carcinoma. Vanillic acid at a dosage of 200 mg/kg body weight was orally
      administrated to the hamsters for 14 weeks. The status of lipid peroxidation and
      antioxidants were measured in the plasma and buccal mucosa of hamsters using
      specific colorimetric methods. RESULTS: Altered levels of lipid peroxidation by
      products {Thiobarbituric Acid Reactive Substances (TBARS)} and disturbances in
      antioxidants status {Superoxide Dismutase (SOD), Catalase (CAT), Glutathione
      Peroxidase (GPx), vitamin E, vitamin C and reduced Glutathione (GSH)} were
      observed in the plasma and buccal mucosa tissues of hamsters treated with DMBA
      alone. Vanillic acid (200 mg/kg bw p.o) significantly restored the above
      mentioned plasma and buccal mucosa biochemical variables to near normal range in
      DMBA treated hamsters. CONCLUSION: Present findings thus confirm the anti-lipid
      peroxidative and antioxidant efficacy of vanillic acid in DMBA induced hamster
      buccal pouch carcinogenesis.

PMID- 28511375
TI  - Impact of Nutritional Status on Cognition in Institutionalized Orphans: A Pilot
      Study.
AB  - INTRODUCTION: Proper nutrition is critical for maximizing brain function and
      enhancing learning. There is accumulating evidence that early malnutrition,
      marked by stunting, is associated with long-term deficits in cognitive and
      academic performance, even when social and psychological differences are
      controlled. All over the world, children living without permanent parental care
      are at a heightened risk for under-nutrition, putting their health and
      development in great jeopardy. AIM: To assess the nutritional and cognitive
      status in institutionalized orphans which might help to formulate effective
      interventions for improving the nutritional status of vulnerable children in
      future. MATERIALS AND METHODS: This cross-sectional, study included 70 children
      (35 orphans and 35 non-orphans). Their anthropometric measurements (height,
      weight, and BMI) were measured and cognition was assessed using subsets of
      Wechsler Intelligence Scale for Children-Revised (WISC-R): Block design and Digit
      span. The data obtained was subjected to descriptive statistical analysis.
      RESULTS: 18.57% (13) of children had stunting, 15.71% (11) had wasting, 22.86%
      (16) were underweight, and 17.14% (12) showed thinness. Mean+/-SD of Block design
      in non-orphans was significantly higher compared to orphans (p-value 0.05).
      Mean+/-SD of Digit span in non-orphans was significantly higher compared to
      orphans (p-value 0.000). For Block design, there was moderate positive
      correlation with nutritional status based on Z-scores (p-value <0.05). Digit span
      also showed moderate positive correlation (p-value <0.05). CONCLUSION: The
      results of our study indicate that children in orphanages have high rates of both
      malnutrition and cognitive delay compared to the non-orphans and there was a
      direct correlation between both the variables. If orphanages are here to stay as
      a last resort for children deprived of a family there is an urgent need to
      improve the institutional environment in order to foster the development of
      millions of children in orphanages around the world.

PMID- 28511376
TI  - Nerve Conduction Study on Sural Nerve among Nepalese Tailors Using Mechanical
      Sewing Machine.
AB  - INTRODUCTION: The use of new technologies and innovations are out of access for
      people living in a developing country like Nepal. The mechanical sewing machine
      is still in existence at a large scale and dominant all over the country.
      Tailoring is one of the major occupations adopted by skilled people with lower
      socioeconomic status and education level. Sural nerves of both right and left
      legs are exposed to strenuous and chronic stress exerted by chronic paddling of
      mechanical sewing machine with legs. AIM: To evaluate the influence of chronic
      and strenuous paddling on right and left sural nerves. MATERIALS AND METHODS: The
      study recruited 30 healthy male tailors with median age {34(31-37.25)} years
      (study group), and, 30 healthy male volunteers with age {34(32-36.25)} years
      (control group). Anthropometric measurements (age, height, weight, BMI and length
      of both right and left legs) as well as cardio respiratory measurements [Systolic
      Blood Pressure (SBP), Dystolic Blood Pressure (DBP), Pules Rate (PR) and
      Respiratory Rate (RR)] were recorded for each subject. Standard nerve conduction
      techniques using constant measured distances were applied to evaluate sural nerve
      (sensory) in both legs of each individual. The differences in variables between
      the study and control groups were tested using Student's t-test for parametric
      variables and Mann-Whitney U test for nonparametric variables. A p-value of <=
      0.05 was considered significant. RESULTS: Age, height, weight, body mass index
      and leg length were not significantly different between tailors and control
      groups. Cardio respiratory measurements (SBP, DBP, PR and RR) were also not
      significantly altered between both the groups. The sensory nerve conduction
      velocities (m/s) of the right {44.23(42.72-47.83) vs 50(46- 54)} and left sural
      nerves {45.97+/-5.86 vs 50.67+/-6.59} m/s were found significantly reduced in
      tailors in comparison to control group. Similarly amplitudes (MUv) of right sural
      (20.75+/-5.42 vs 24.10+/-5.45) and left sural nerves {18.2(12.43-21.8) vs
      32.0(26.5-35.25)} were significantly less in tailors in comparison to control
      group whereas, latencies (ms) of right sural {2.6(2.2-2.7) vs 2.0(2.0-2.250} and
      left sural nerve {2.4(2.07-2.72) vs 2.0(2.0-2.0)} were found significantly high
      in tailors as compared with control group. CONCLUSION: Operating mechanical
      sewing machine by paddling chronically and arduously could have attributed to
      abnormal nerve conduction study parameters due to vibration effect of the machine
      on right and left sural nerves. The results of present study follow the trend
      towards presymptomatic or asymptomatic neuropathy similar to subclinical
      neuropathy.

PMID- 28511377
TI  - An Analysis of Dynamic Pulmonary Functions of Hypothyroid Patients.
AB  - INTRODUCTION: Hypothyroidism is a silent epidemic of our times. In India, the
      prevalence of hypothyroidism is 11%. The effect of hypothyroidism on respiratory
      system is debatable with studies suggesting both obstructive and restrictive
      disease patterns. The symptoms range from mild dyspnoea to life-threatening
      respiratory failure. This study emphasizes the effect of hypothyroidism on
      dynamic respiratory functions. AIM: To find out the changes in dynamic
      respiratory functions (FVC, FEV1, FEV1% and PEFR) in both male and female
      hypothyroid patients within age group of 18-45 years. MATERIALS AND METHODS: This
      cross-sectional study was conducted in Jubilee Mission Medical College, Thrissur,
      Kerala, India. Total number of 60 newly detected cases of both sexes in 18-45
      years age group attending endocrinology outpatient department were enrolled.
      Patients with previous respiratory diseases and history of smoking were excluded.
      Proforma was filled up followed by clinical examination. Spirometry was performed
      using a computerised spirometer 'microQuark'. The data was analysed by paired t
      test and Analysis of Variance (ANOVA) test. RESULTS: The mean of the observed
      values in all the dynamic pulmonary parameters showed highly significant
      difference from the predicted mean of the parameters (p<0.001). They also
      decreased considerably with age, gender and BMI which were statistically
      significant (p<0.05). CONCLUSION: The above findings suggest that respiratory
      abnormality in newly detected cases of hypothyroidism shows a mixed pattern. This
      highlights that while investigating a patient with respiratory disorder, the
      thyroid status should always be probed into, as the effects of hypothyroidism can
      be reversed with proper treatment.

PMID- 28511378
TI  - Cortical Potentials Prior to Movement in Parkinson's Disease.
AB  - INTRODUCTION: Recording cortical potentials prior to movement
      (bereitschaftspotentials, BP) offer a good non invasive method for studying
      activity of motor related cortices in Parkinson's Disease (PD). Dopaminergic
      medications provide some symptomatic relief in advanced stages but they do not
      stop the progression of the disease. Assessing BP may be a good idea to see the
      response of anti PD drugs. It remains unclear whether the anti PD medications
      also improve cortical activity prior to movement even in advanced stages of the
      disease. AIM: In this study we recorded scalp BP in patients with varying grades
      of severity to study the relationship between disease severity and various
      components of BP. MATERIALS AND METHODS: We successfully recorded BP at Cz, C3
      and C4 sites during self-initiated 100 right wrist movements in 12 male patients
      with PD having severity Hoehn and Yahn (H&Y) scale 4 (PD3 group). These
      potentials were compared with age matched patients with H&Y scale 2 (PD1) and
      scale 3 (PD2) and also with age matched healthy controls. RESULTS: We found
      flatter waveforms with increasing severity of disease. Amplitude is first to be
      affected in mild severity as compared to controls (p=0.011); while with
      increasing severity early as well as late part of potentials is affected. Such
      changes are prominently seen at Cz site across the groups. CONCLUSION: These
      findings imply that there is increasing defect in cortical activity during
      movement especially in supplementary motor area with increasing severity in PD in
      spite of dopaminergic medications. This dynamic nature of dysfunction in
      supplementary motor cortices must be taken in account while treating advanced
      cases using newer stimulation techniques.

PMID- 28511379
TI  - Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis.
AB  - INTRODUCTION: Atopic Dermatitis (AD) is a recurrent chronic condition associated
      with microorganism and their interaction with the susceptible host. Malassezia
      yeast is a known commensal which is thought to provoke the recurrent episodes of
      symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties
      along with defective skin barrier in such host, results in disease manifestation.
      Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN gamma genes
      of the host and its relation with susceptibility to Malassezia infection. AIM: To
      isolate Malassezia yeast from AD patients and compare the genetic susceptibility
      of the host by correlating the cytokine gene polymorphism with the control
      subjects. MATERIALS AND METHODS: Study was conducted from January 2012 to January
      2013. It was a prospective observational study done in Department of Microbiology
      and Department of Dermatology and Venereology in University College of Medical
      Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD.
      Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and
      Modified Dixon Agar (MDA) and isolated were identified as per conventional
      phenotypic methods. Genomic DNA was extracted from blood samples collected from
      all study subjects. Cytokine genotyping was carried out by Amplification
      Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence
      specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-gamma+874A/T) in
      two cytokine genes were assessed in all the patients and healthy controls.
      STATISTICAL ANALYSIS: Chi-Square Test or Fisher's-Exact Test and Bonferroni's
      correction. RESULTS: In AD group, Malassezia yeasts were cultured in 24 out of 38
      samples and thus the identification rate was 63.1 percent as compared to healthy
      group, 52.6 percent (20/38). Significant difference in allele, or genotype
      distribution were observed in IL10-819/592C/T and IFN-gamma+874A/T gene
      polymorphism in AD group. CONCLUSION: Higher isolation rate in cases as compared
      to control group highlights the implication of Malassezia in AD. Association
      between specific cytokine gene polymorphism and clinical outcome was found to be
      significant in study group. The result of cytokine gene polymorphism in the
      present study demonstrated susceptibility of host to Malassezia infection.

PMID- 28511381
TI  - Prevalence of Carbapenem Resistant Non-Fermenting Gram Negative Bacterial
      Infection and Identification of Carbapenemase Producing NFGNB Isolates by Simple
      Phenotypic Tests.
AB  - INTRODUCTION: Non-Fermenting Gram negative bacilli (NFGNB) are emerging multi
      drug resistant pathogens causing nosocomial infections. In recent years,
      carbapenem resistance in NFGNB has increased due to a variety of drug resistance
      mechanisms, the most common being production of carbapenemases. AIM: To detect
      carbapenemase and metallo-beta-lactamase (MBL) production in NFGNBs by four
      phenotypic tests and to compare the various phenotypic methods for detection of
      carbapenemase and MBL production in nosocomial NFGNB isolates. MATERIALS AND
      METHODS: It is a cross sectional study carried out in the department of
      Microbiology, Chennai Medical College Hospital and Research Center, Irungalur,
      Trichy between January 2015 and December 2015. Out of the 598 NFGNB isolated from
      all the 5402 heterogenous clinical samples that were processed, 52 (8.7%) NFGNB
      showed resistance or intermediate sensitivity to meropenem as tested by disc
      diffusion assay. All the 52 isolates were subjected to four different phenotypic
      tests for carbapenemase and MBL detection, which included Modified Hodge Test
      (MHT), Meropenem-EDTA Disc Synergy (EDS) test, Meropenem-EDTA Combined Disc Test
      (CDT) and Growth on CHROMagar KPC. RESULTS: Among the 52 isolates, 29 (55.77%)
      were MHT positive and 49 (94.23%) were positive for growth on CHROMEagar KPC
      which were identified as carbapenemase producers. 44 (84.61%) were EDS positive
      and 46 (88.46%) were CDT positive which were identified as metallo-beta-lactamase
      producers. CONCLUSION: The presence of these resistant bugs strongly suggests the
      need to prevent their further spread by implementation of strict infection
      control measures and regular surveillance to check their outcome. Growth on
      CHROMagar KPC is the test that has picked up more number of carbapenem resistant
      isolates as carbapenemase and metallo-beta-lactamase producers among the four
      tests. It is also cheap and easy to perform, making it the most reliable test for
      routine screening of carbapenemase and MBL producers in clinical laboratories.

PMID- 28511380
TI  - Fungal Profile of Vulvovaginal Candidiasis in a Tertiary Care Hospital.
AB  - INTRODUCTION: Vulvovaginal Candidiasis (VVC) is a common medical health problem
      of adult women. It is most commonly caused by Candida albicans. But there is a
      change in fungal profile. Sabouraud's Dextrose Agar (SDA) is the most common
      culture medium used where mixed fungal infection may be missed. It can be
      detected easily by using chromogenic culture medium. AIM: To know the fungal
      profile of vulvovaginal candidiasis using Candida CHROMagar and antifungal
      susceptibility pattern in patients attending tertiary care hospital. MATERIALS
      AND METHODS: Culture confirmed cases of VVC presented at Department of Obstetrics
      and Gynaecology of Jawaharlal Institute of Postgraduate Medical Education and
      Research (JIPMER), Puducherry, India, from July 2015 to December 2015 were
      included in the cross-sectional study. Two high vaginal swabs were collected and
      inoculated on SDA and Candida CHROMagar (Hi-Media, Mumbai, India). After
      overnight incubation the colonies were counted and colour of the colonies were
      recorded from Candida CHROMagar. Candida spp. were identified by sugar
      fermentation and assimilation tests and other conventional tests. Antifungal
      susceptibility tests were performed by the disc diffusion method using
      fluconazole (25 MUg) and voriconazole (1MUg) as per the Clinical and Laboratory
      Standards Institute (CLSI - M44-A2) guidelines. RESULTS: A total of 50 culture
      confirmed (23.7%) cases were detected from 211 clinically suspected VVC cases.
      Candida glabrata (45.1%) was the most common isolate, followed by
      Candidatropicalis (23.5%), Candida albicans (17.6%), Candida krusei (9.8%) and
      Candida parapsilosis (3.9%). One mixed infection of C. glabrata and C. albicans
      was identified on Candida CHROMagar. Mixed fungal infection was observed in 2% of
      positive culture and 0.5% of VVC cases. The antifungal susceptibility testing
      revealed that 15.7% and 9.8% isolates of Candida spp. were resistant and
      Susceptible Dose Dependent (S-DD) respectively to fluconazole. The increase
      resistant against fluconazole was because of increased isolation of C. glabrata
      strains. All strains of Candida spp. were susceptible to voriconazole.
      CONCLUSION: C. glabrata was the most common causative agent of VVC in a tertiary
      care hospital. Chromogenic culture medium facilitates detection of mixed fungal
      infection. In vitro susceptibility testing should be used to guide the treatment
      especially in cases of non-albicans Candidiasis.

PMID- 28511383
TI  - Study on MICs of Tigecycline in Clinical Isolates of Carbapenem Resistant
      Enterobacteriaceae (CRE) at a Tertiary Care Centre in North India.
AB  - INTRODUCTION: Members of family Enterobacteriaceae are the most common Gram
      negative bacteria isolated from clinical samples. Those Enterobacteriaceae which
      have acquired resistance to all beta-lactams antibiotics including the
      carbapenems are considered as Carbapenem Resistant Enterobacteriaceae (CRE).
      These CRE isolates are often resistant to most other classes of antimicrobials as
      well, making their treatment a great challenge. Tigecycline is one of the last
      resort antimicrobials against such multidrug resistant bacteria. Decreased
      tigecycline susceptibility mediated by efflux pump systems is being reported in
      clinical strains of Enterobacteriaceae. Minimum Inhibitory Concentration (MIC)
      data would prove useful in managing infections by these multidrug resistant
      bacteria and optimizing use of tigecycline. AIM: To evaluate the MIC values of
      tigecycline against carbapenem resistant Escherichia coli and Klebsiella
      pneumoniae isolates. MATERIALS AND METHODS: This prospective study was carried
      out from January 2015 to December 2015 at the Department of Microbiology, Era's
      Lucknow Medical College and Hospital (ELMCH), Lucknow, Uttar Pradesh, India.
      Antimicrobial susceptibility by disk diffusion (Kirby-bauer) was done for 491 E.
      coli and K. pneumoniae strains isolated from 1606 samples collected from patients
      admitted in various wards and ICUs. Imipenem, meropenem and ertapenem 10 MUg
      disks were used for testing of sensitivity to carbapenems. In all isolates,
      Tigecycline 15 MUg (Hi-Media) disk was used to screen for tigecycline resistance.
      In CRE isolates, MICs of tigecycline were determined by E-test (Ezy MIC TM TG
      strips, Hi Media) and interpreted using European Committee on Antimicrobial
      Susceptibility Testing (EUCAST) 2016 guidelines. RESULTS: Out of 491 isolates
      tested, 186 (37.9%) were found to be CRE showing resistance to at least one of
      the three carbapenems tested and these included 99 E.coli and 87 K. pneumoniae.
      Sensitivity pattern of these two bacterial isolates shows a high level of
      resistance to most classes of antimicrobials. MIC testing for tigecycline was
      carried out in 144 CRE isolates and tigecycline resistance (MIC >2 MUg/ml) was
      seen in 12 (8.3%) isolates (eight K.pneumoniae and four E. coli). Eight other
      isolates were found to have MIC of 2 MUg/ml and thus the overall prevalence of
      isolates with decreased susceptibility was 20 (13.9%). CONCLUSION: A high
      prevalence of carbapenem resistance coupled with high tigecycline MICs in
      clinical isolates of E.coli and K. pneumoniae highlights the judicious use of a
      combination of antimicrobials. Routine in vitro sensitivity testing to evaluate
      the clinical utility of tigecycline against such resistant Enterobacteriaceae is
      warranted.

PMID- 28511384
TI  - Community Acquired Burkholderia cepacia Bacteraemia Presenting as MODS in an
      Immunocompetent Individual: An Unusual Case.
AB  - Burkholderia cepacia has been recognized as a group of highly virulent organisms
      known as Burkholderia cepacia complex (Bcc). Bcc are ubiquitous in nature and
      most commonly found in moist environment, on plant roots and soil. Because of its
      high intrinsic antibiotic resistance, Bcc is a major cause of morbidity and
      mortality in hospitalized patients. It is reported most commonly in
      immunocompromised patients especially in patients with cystic fibrosis. Here, we
      report a rare case report of bacteraemia by Burkholderia cepacia in an
      immunocompetent male, who presented with fever and Multiple Organ Dysfunction
      Syndrome (MODS). Burkholderia cepacia was isolated from his blood culture, which
      he acquired from his work place. He was treated successfully and discharged after
      negative blood culture.

PMID- 28511382
TI  - Rapid Identification of Vancomycin Resistant Enterococcus Faecalis Clinical
      Isolates using a Sugar Fermentation Method.
AB  - INTRODUCTION: Vancomycin Resistant Enterococci (VRE) can be found all over the
      world. Thus, rapid detection of the isolates could be of high importance in the
      treatment or prevention of the associated disease. AIM: To measure the turanose
      fermentation in Enterococcus faecalis clinical isolates for rapid differentiation
      of VRE and Vancomycin-Susceptible E. faecalis (VSE) isolates. MATERIALS AND
      METHODS: Forty E. faecalis samples were isolated from 200 clinical samples in
      Tehran Medical Center, Iran, from October 2012 to December 2012. These isolates
      were detected according to the standard microbial and biochemical tests.
      Detection of VRE isolates was originally performed by disk diffusion using 1 MUg
      vancomycin disk, followed by Polymerase Chain Reaction (PCR) amplification of the
      vanA gene. Finally, the turanose consumption in 1%, 0.7% and 0.5% dilutions was
      detected by a phenotypic method. RESULTS: Among the 40 E. faecalis isolates, 20
      vancomycin-susceptible and 20 vancomycin-resistant E. faecalis were isolated
      according to the disk diffusion and PCR of the vanA gene. There was a
      considerable difference between VRE and VSE isolates in 0.7% dilution of
      turanose. However, there was no significant difference between VRE and VSE in 1%
      and 0.5% dilutions of turanose. CONCLUSION: Since detection of VRE isolates is of
      high importance, especially in nosocomial infections, phenotypic methods may be
      highly useful for this purpose. In conclusion, our data indicate that VRE
      isolated from clinical samples could be distinguished from VSE isolates by
      turanose fermentation at dilution 0.7%.

PMID- 28511385
TI  - Intra-operative Diagnosis of Breast Lesions by Imprint Cytology and Frozen
      Section with Histopathological Correlation.
AB  - INTRODUCTION: The most common malignant tumour among women is breast carcinoma.
      Early lesions of the breast including carcinoma are potentially curable if
      treated properly in the era of breast conservative therapy. For this purpose
      different diagnostic strategies are in practice. Intra operative Imprint Cytology
      (IC) and Frozen Section (FS) have a role in spite of the intense recognition of
      aspiration cytology in the following settings: inconclusive cytological/core
      biopsy findings; for evaluation of lumpectomy margins and intra operative nodal
      status. Both IC and FS are dependable intra operative diagnostic consultation
      modalities and provide accurate results in minutes thereby making appropriate
      therapeutic decision. AIM: To study the IC and FS features of breast lesions with
      correlation of final Histopathologic (HP) diagnosis and to determine its
      diagnostic accuracy. MATERIALS AND METHODS: This was a descriptive cross
      sectional study conducted in the Department of Pathology, JSS Medical College,
      JSS University, Mysuru over a period of two years (October 2011-September 2013).
      A total of 62 cases of surgically resected breast specimens were evaluated for
      features of IC, FS and correlation with HP diagnosis. After describing gross
      features, representative tissue fragment was taken, three imprint smears were
      made and same tissue fragment was subjected to FS and later for routine HP
      processing. Slides prepared by IC, FS were interpreted and later correlated with
      HP diagnosis. Statistical analysis was done with SPSS for windows (version 16.0)
      by applying appropriate tests. RESULTS: Out of 62 cases, 33(53.23%) were
      malignant and 29(46.77%) were benign. Sensitivity, specificity and accuracy of IC
      were 100%, 96.43% and 98.36% and for FS were 100%, 96.55% and 98.39%
      respectively. p-value for both were <0.001 indicating significant correlation
      with HP study. CONCLUSION: IC is a simple, accurate, rapid and cost effective
      diagnostic tool intra operatively where services for FS are not available. It
      preserves crisp cellular and nuclear detail. FS tissue architecture strongly
      approximates permanent HP sections but is frequently hampered by freezing
      artifact. But FS is able to differentiate carcinoma in situ and infiltrative
      lesions from benign breast lesions. Thus, IC and FS together offer a more
      reliable diagnosis; hence, it is always useful to prepare both the slides intra
      operatively. HP study still remains the gold standard in final diagnosis of any
      breast lesion. In surgical pathology, the correlation of intra operative IC and
      FS diagnosis with the final HP diagnosis form an essential part of quality
      assurance activity.

PMID- 28511386
TI  - Assessment of Disease Severity and Role of Cytomegalo Virus Infection in Patients
      with Ulcerative Colitis.
AB  - INTRODUCTION: Course of Ulcerative Colitis is characterized by intermittent
      flares interposed between variable periods of remission. Identification of
      exacerbating factors and appropriate assessment of disease activity are crucial
      in deciding the choice of treatment. AIM: To evaluate various clinical,
      endoscopic and histological parameters in assessing disease activity and to find
      out various risk factors involved in the exacerbation of ulcerative colitis
      especially the role of Cytomegalo Virus (CMV) infection. MATERIALS AND METHODS:
      It was a prospective study of patients diagnosed as ulcerative colitis presenting
      with acute exacerbation of symptoms (cases) and those who were in remission
      (controls). A detailed evaluation of the disease history including personal
      history, treatment compliance and clinical disease severity were noted.
      Investigations including blood routine, endoscopic examination with biopsy,
      histopathological examination and immunohistochemistry for CMV were done on the
      biopsy sample. RESULTS: A total of 58 patients with ulcerative colitis were
      studied which included 37 cases and 21 controls. Out of the various clinical and
      demographic parameters, Good treatment compliance (p =0.0003) and Perceived
      Stress Scale (PSS) score (p=0.0001) showed significant difference between cases
      and controls. Basic laboratory parameters {Haemoglobin level, Total Leucocyte
      Count (TLC) and Erythrocyte Sedimentation Rate (ESR)}, clinical disease severity
      predictors (Truelove and Witt's criteria, Mayo score and endoscopic disease
      severity grade) and Geboes histological scoring showed significant difference
      between cases and controls. The prevalence of CMV colitis in our study was only
      5.4% (two cases). CONCLUSION: Clinical and endoscopic disease severity indicators
      can be used as predictors of histological activity in ulcerative colitis. Poor
      treatment compliance and stress are important risk factors for acute exacerbation
      of ulcerative colitis. Clinicians should be aware of the possibility of
      concurrent CMV infection while treating patients with acute exacerbation of
      ulcerative colitis not responding to the conventional management. Reduced
      prevalence of CMV colitis in cases of acute exacerbation of ulcerative colitis in
      our study may be due to the small sample size, reduced number of steroid
      dependent cases or reduced severity of our cases.

PMID- 28511387
TI  - Erythrocyte Alloimmunization and Autoimmunization among Blood Donors and
      Recipients visiting a Tertiary Care Hospital.
AB  - INTRODUCTION: The ultimate aim of pretransfusion testing is the acceptable
      survival of donor red cells in recipient's body and antibody detection plays a
      critical role in achieving the same. The cornerstone of antibody detection method
      is detecting an unexpected antibody as against the expected antibodies of ABO
      blood group system. Autoantibodies can also interfere with the detection of
      clinically significant alloantibodies. AIM: To study the frequency of
      alloantibodies and autoantibodies in the healthy blood donors and patient
      population visiting our hospital. MATERIALS AND METHODS: The Column Agglutination
      Technology (CAT) was used for ABO RhD blood grouping, Direct Antiglobulin Test
      (DAT), Autocontrol (AC), Indirect Antiglobulin Test (IAT) and red cell antibody
      screening and the unexpected reactions in any of these tests were recorded for
      further evaluation. Ethylene Diamine Tetra Acetic Acid (EDTA) blood samples were
      used for all these tests for both blood donors and admitted patients. The CAT was
      exercised for the blood grouping (using ABD-Reverse Diluent cassettes) and
      antibody screening (using 0.8% Surgiscreen, Ortho Clinical Diagnostics Limited,
      USA and Low Ionic Strength Saline Ortho BLISS with AHG cassettes) on the
      automated immunohaematology platform ORTHO AutoVue(r) Innova system (Ortho
      Clinical Diagnostics Limited, USA). RESULTS: Among all blood donors (n=6350),
      seven (0.11%) donors had showed unexpected reaction. Of these, four had positive
      antibody screen (three having naturally occuring antibodies 2=anti-M, 1=anti-Lea
      and 1=inconclusive) and the other three had positive DAT. Of all the patient
      samples (n=6136) screened for irregular red cell antibodies, four (0.06%)
      patients were found to have unexpected reaction revealing one (0.02%) with anti-M
      antibody and the other three (0.05%) had autoantibodies in their serum.
      CONCLUSION: The combined prevalence for both blood donor and recipient population
      (n=12,486) was found to be 0.11% at our center. The alloimmunisation among
      patient population was found to be lower than many other studies worldwide as our
      hospital does not cater to multitransfused or transfusion dependant patients with
      haematological disorders and majorly elective surgery patients with no history of
      previous blood transfusions visit our hospital.

PMID- 28511388
TI  - Leishman-Giemsa Cocktail - Is it an Effective Stain for Air Dried Cytology
      Smears.
AB  - INTRODUCTION: Air dried cytology smears are stained routinely with Romanowsky
      stains so that the relative cell size, nuclear size, cytoplasmic details, smear
      background elements and intercellular matrix components are better appreciated. A
      variety of modified Romanowsky stains are used in cytology. Leishman-Giemsa (LG)
      cocktail is one of the new staining techniques which can be used for staining the
      air dried cytology smears. AIM: To evaluate the quality of staining of LG
      cocktail on air dried smears and to compare the quality of staining of LG
      cocktail with May Grunwald Giemsa (MGG) which is the most commonly used stain in
      cytology. MATERIALS AND METHODS: The present prospective comparative study was
      carried out with 100 cases and two extra smears were prepared for each case and
      stained with MGG and LG cocktail stains. The stained slides were blinded and were
      evaluated for the staining characteristics of the nucleus, cytoplasm and
      background staining. Based on this, scoring was done by two pathologists
      independently. Quality Index (QI) was calculated by dividing the scores obtained
      with the total score possible. RESULTS: LG cocktail stained slides were excellent
      in cytoplasmic staining, granularity, nuclear morphology, background material
      staining and overall staining characteristics. QI of LG cocktail was 0.8 while
      that of MGG was 0.59. CONCLUSION: Staining of air dried smears by LG cocktail has
      a good QI. It is also cheaper, requires short duration for staining as compared
      to MGG. Hence, LG cocktail can be an effective replacement for MGG for staining
      the air dried cytology smears.

PMID- 28511389
TI  - Variability of Iron Load in Patients of Sickle Cell Anaemia (HbSS): A study from
      Eastern India.
AB  - INTRODUCTION: Sickle Cell Anaemia (SCA) is one of the commonest
      haemoglobinopathies due to a point mutation (A->T) of the beta-globin gene. Out
      of five haplotypes, the Arab-Indian haplotype present in India is one of the
      least severe phenotype and least studied also. It is characterized by lifelong
      haemolytic anaemia requiring red cell transfusion leading to iron overload. In
      contrast, there is very high incidence of deficiency of iron, folic acid and
      vitamin B12. AIM: Our objective was to access the Iron status of SCA patients and
      to find its correlation with various parameters like red cell transfusion,
      haemolysis and serum hepcidin. MATERIALS AND METHODS: This was a cross-sectional
      study conducted on 208 patients for a period of five years. Complete Blood Count
      (CBC), iron profile, haemolytic parameters and transfusion requirement were
      studied and data compared with 52 healthy controls. RESULTS: Few patients (9.6%)
      revealed significant iron overload (Serum ferritin > 1000 ng/ml). In majority
      (80.8%) it was either normal or border line raised (300 to 1000 ng/ml) or iron
      deficiency was noted in a small fraction (9.6%). Frequency of transfusion is the
      principal factor which positively correlated with level of iron load (p<0.001)
      while parameters of haemolysis and serum hepcidin level play an insignificant
      role in this context (p= 0.0634). CONCLUSION: This study supports the notion that
      the presentation of SCA patients in India is of "Viscosity - Vaso-Occlusive
      Crisis (VOC) phenotype" with high incidence of VOC, low haemolytic rate and
      transfusion requirement. Iron deficiency may be present in SCA patients requiring
      Iron supplementation. We suggest further studies to establish the role of
      hepcidin, ferroportin and other factors that control iron absorption in these
      patients.

PMID- 28511390
TI  - Expression of Angiogenic Factors in Psoriasis Vulgaris.
AB  - INTRODUCTION: Psoriasis is a chronic inflammatory skin disease characterized by
      epidermal hyperproliferation, abnormal differentiation and inflammatory
      infiltration in the dermis. The dermal microvascular expansion associated with
      abnormal orientation and dilatation of capillaries in the biopsies of the
      psoriatic skin suggest that the disease is dependent on angiogenesis. AIM: To
      analyze and compare the immunohistochemical expression of angiogenic factors -
      Vascular Endothelial Growth Factor (VEGF), von Willebrand Factor (vWF) and CD 34
      in skin biopsies of psoriasis cases with control skin samples; and to correlate
      the expression of angiogenic factors with Psoriasis Area and Severity Clinical
      Index (PASI SCORE). MATERIALS AND METHODS: This was a prospective case control
      study conducted over a period of 15 months. Thirty-two psoriasis cases and thirty
      control skin samples were included in the study. Skin biopsy specimen was taken
      from clinically diagnosed psoriasis cases who did not receive any treatment. The
      diagnosis of psoriasis vulgaris was confirmed after microscopic examination.
      Immunohistochemical expression for VEGF, vWF and CD 34 was studied. RESULTS: VEGF
      expression in epidermis was significantly higher in cases when compared to
      control skin (p <0.01). CD 34 expression was significantly upregulated in cases
      when compared to controls (p<0.01). Von Willebrand factor expression was weak in
      both the cases and the controls. Significant correlation between the expression
      of VEGF and PASI score (r=0.944; p<0.01), and expression of CD 34 and PASI score
      was observed (r=0.942; p<0.01). CONCLUSION: In the present study, significant
      overexpression of VEGF and CD 34 was noted in cases when compared to controls.
      The keratinocytes in the psoriatic skin lesions were recognized as a source of
      pro-angiogenic cytokines namely the VEGF and other growth factors which promotes
      angiogenesis in psoriatic plaque. Angiogenesis plays an important role in genesis
      and development of psoriasis vulgaris. Therefore, development of targeted anti
      angiogenic therapy might be beneficial for this chronic disabling dermatological
      disease.

PMID- 28511391
TI  - Utility of Modified Ultrafast Papanicolaou Stain in Cytological Diagnosis.
AB  - INTRODUCTION: Need for minimal turnaround time for assessing Fine Needle
      Aspiration Cytology (FNAC) has encouraged innovations in staining techniques that
      require lesser staining time with unequivocal cell morphology. The standard
      protocol for conventional Papanicolaou (PAP) stain requires about 40 minutes. To
      overcome this, Ultrafast Papanicolaou (UFP) stain was introduced which reduces
      staining time to 90 seconds and also enhances the quality. However, reagents
      required for this were not easily available hence, Modified Ultrafast
      Papanicolaou (MUFP) stain was introduced subsequently. AIM: To assess the
      efficacy of MUFP staining by comparing the quality of MUFP stain with
      conventional PAP stain. MATERIALS AND METHODS: FNAC procedure was performed by
      using 10 ml disposable syringe and 22-23 G needle. Total 131 FNAC cases were
      studied which were lymph node (30), thyroid (38), breast (22), skin and soft
      tissue (24), salivary gland (11) and visceral organs (6). Two smears were
      prepared and stained by MUFP and conventional PAP stain. Scores were given on
      four parameters: background of smears, overall staining pattern, cell morphology
      and nuclear staining. Quality Index (QI) was calculated from ratio of total score
      achieved to maximum score possible. Statistical analysis using chi square test
      was applied to each of the four parameters before obtaining the QI in both
      stains. Students t-test was applied to evaluate the efficacy of MUFP in
      comparison with conventional PAP stain. RESULTS: The QI of MUFP for thyroid,
      breast, lymph node, skin and soft tissue, salivary gland and visceral organs was
      0.89, 0.85, 0.89, 0.83, 0.92, and 0.78 respectively. Compared to conventional PAP
      stain QI of MUFP smears was better in all except visceral organ cases and was
      statistically significant. MUFP showed clear red blood cell background,
      transparent cytoplasm and crisp nuclear features. CONCLUSION: MUFP is fast,
      reliable and can be done with locally available reagents with unequivocal
      morphology which is the need of the hour for a cytopathology set-up.

PMID- 28511392
TI  - The Diagnostic Value of Urine Lipoarabinomannan (LAM) Antigen in Childhood
      Tuberculosis.
AB  - INTRODUCTION: Diagnosis of Tuberculosis (TB) in children is difficult because the
      clinical presentation is not specific, the chest X-ray interpretation has low
      accuracy and sputum sample is difficult to obtain. Antigen detection test such as
      rapid urine LAM is a non-invasive alternative for diagnosing TB .
      Lipoarabinomannan (LAM) is the main component of M.tuberculosis cell wall. AIM:
      To determine the diagnostic value of urinary LAM antigen for diagnosis of
      childhood TB. MATERIALS AND METHODS: In the present cross-sectional study,
      subjects were included using consecutive sampling method. All the children aged 0
      14 years Suspected of pulmonary or extra pulmonary TB suffering from cough more
      than two weeks, fever without clear aetiology, loss of body weight or poor weight
      gain, fatigue, malaise, chronic lymph node enlargement, spine angulation, joint
      swelling and had history of contact with positive sputum smear adult TB patient
      were enrolled in the study. Pulmonary and extra pulmonary diagnosis was based on
      clinical presentation, Tuberculin Skin Test (TST), chest X-ray, Acid Fast
      Bacillus (AFB) staining and or sputum culture. Urinary LAM level was measured by
      using Enzyme-Linked Immunosorbent Assay (ELISA). Cut off value and Area Under the
      Curve (AUC) were determined using ROC statistical analysis (SPSS 21.0).
      Sensitivity and specificity was measured from 2x2 cross table. RESULTS: Out of 61
      subjects suspected as TB, 49 (80.3%) were eventually diagnosed with TB. Of those
      diagnosed with TB, 21 (42.9%) were microbiologically confirmed cases either by
      sputum microscopy (34.7%) or culture (8.2%), whereas 28 subjects were unconfirmed
      cases (57.1%). The urinary LAM level was higher in subjects with TB (1.80+1.02)
      mg/l compared to non-TB group (0.46+0.3) mg/l; p<0.001(independent t-test). Urine
      LAM had 83% sensitivity and 85% specificity with cut off value 0.98 mg/l using
      microbiological and clinical confirmation as standard reference and 33%
      sensitivity and 60% specificity with cut off value 1.69 mg/l using
      microbiological confirmation only. CONCLUSION: Urinary LAM has good diagnostic
      value for childhood TB diagnosis.

PMID- 28511393
TI  - Utility of Tru-Cut Biopsy of Breast Lesions - An Experience in a Regional Cancer
      Center of a Developing Country.
AB  - INTRODUCTION: Tru-cut Needle Biopsy (TCB) is an integral part of triple
      assessment of breast cancer, which includes clinical assessment, mammography and
      TCB or Core Needle Biopsy (CNB). The technique is reliable, simple, and
      reproducible, and inexpensive, which can be adapted even for low-income group of
      patients and in developing countries. AIM: This study was done to establish the
      efficacy of TCB of palpable breast lesions in a developing country where
      mammography is not possible in all cases. MATERIALS AND METHODS: A retrospective
      analysis of 892 TCBs was done in AH Regional Cancer Centre, Cuttack, Odisha,
      India where TCBs were performed in patients presenting to outpatient department
      with palpable breast lesions. The H&E stained sections were interpreted by
      pathologists of the same centre. Diagnosis was classified into different
      categories. Immunohistochemistry (IHC) for Estrogen Receptor (ER), Progesterone
      Receptor (PR) and Her-2/neu was done and interpreted by Allred scoring system.
      RESULTS: A total 892 TCBs were analysed with 23 repeat TCBs. There were 13 (1.4%)
      male patients. A total of 747 cases (83.6%) were diagnosed as malignant,
      including 735 carcinomas, nine malignant phyllodes tumour, two angiosarcoma and
      one case of Non-Hodgkin' Lymphoma (NHL). It was possible to diagnose special
      histological types such as lobular carcinoma, metaplastic carcinoma and mucinous
      carcinoma on TCB. A total of 21 cases were diagnosed as carcinoma on repeat
      biopsy. Eight of the 735 TCBs diagnosed as carcinoma were bilateral breast
      cancers, hence actual number of carcinoma cases were 727. IHC was done
      successfully on the paraffin blocks in 260 cases. In this series out of 727
      patients of carcinomas 30% were in young, i.e., below 40 years of age, including
      four cases of carcinoma below 20 years. There were no false positive case in this
      study giving a specificity of 100% and sensitivity was 97%. CONCLUSION: TCBs are
      well tolerated by patients, can be done in OPDs and reduce cost. It is possible
      to give histological diagnosis of carcinoma, lymphoma, phyllodes tumour and
      sarcomas on TCBs. The paraffin blocks of TCBs can be used for IHC study which
      helps the oncologists for preoperative adjuvant therapy.

PMID- 28511394
TI  - Breast Biomarkers-Comparison on Whole Section and Tissue Microarray Section.
AB  - INTRODUCTION: Estrogen Receptor (ER), Progesterone Receptor (PR) and Her2/neu are
      routinely studied markers for breast carcinoma. Analysis of these biomarkers is
      traditionally done by Immunohistochemistry (IHC) on whole sections. These markers
      can also be studied on Tissue Microarray (TMA) sections. Tissue microarray is a
      technique where core samples from different paraffin blocks are arrayed on a
      single recipient block which can then be cut to yield a single section with
      multiple cores in it. AIM: To compare ER, PR and Her2/neu on TMA sections with
      whole sections and to determine the concordance of results between the two
      methods. MATERIALS AND METHODS: A TMA block was constructed by punching out 2 mm
      cores from appropriately marked paraffin blocks of 53 breast carcinoma cases and
      embedding them in the recipient block. Immunostaining of TMA sections and whole
      sections were performed for ER, PR and Her2/neu and the results were compared.
      Statistical analysis was done using chi square test/Fisher-Exact test. Kappa co
      efficient, Jaccard Index and G-Index were computed. RESULTS: Infiltrating Ductal
      Carcinoma-No Special Type (IDC-NST) was the predominant type of carcinoma and
      most of the tumours were of Grade II and III. Majority, 38/53 (71.7%) were ER/PR
      positive and Her2 negative and 9/53 (17%) cases were triple negative. Good
      concordance between whole sections and TMA sections were noted with kappa value
      for ER, PR and Her2/neu being 0.671, 0.754, 1.000 respectively which was
      statistically significant. CONCLUSION: Immunostaining for ER, PR and Her2/neu
      done on TMA section using single 2 mm core were comparable with conventional
      whole section scores. Thus, TMA is a reliable method for evaluating these
      biomarkers with the advantage of being time and cost effective.

PMID- 28511395
TI  - Clinical and Cytological Spectrum of Granulomatous Mastitis and Utility of FNAC
      in Picking up Tubercular Mastitis: An Eight-Year Study.
AB  - INTRODUCTION: Granulomatous Mastitis (GM) is a rare, benign, inflammatory disease
      of the breast. It is a well known mimicker of malignancy, clinically and
      radiologically. Patients are often subjected to number of tests for the right
      diagnosis. Non-specific Granulomatous Mastitis (NGM) and Tubercular Mastitis
      (TBM) are chief among the various causes of GM. They are important to be
      diagnosed early as their treatment varies significantly. Fine Needle Aspiration
      Cytology (FNAC) is simple, patient friendly and primary investigation modality in
      cases of lump in breast. AIM: To find out the utility of FNAC in differentiating
      NGM and TBM. MATERIALS AND METHODS: All cases of granulomatous mastitis diagnosed
      on cytology over eight years were retrospectively retrieved. The clinical and
      radiological history was obtained from the patient file. The slides were stained
      with haematoxylin and eosin stain as well as Leishman stains. Special stains like
      Periodic Acid Schiff (PAS) and Ziehl Neelsen (ZN) stain were used for fungus and
      Mycobacteriumtuberculosis respectively. Histopathological correlation of the
      available cases was done. Clinical presentation and cytological morphology of
      individual cases was studied in detail. RESULTS: Twenty one cases of GM obtained,
      of which 16 were NGM and five were TBM. Both diseases were common among young
      reproductive women who presented with unilateral breast lump of varying duration.
      Almost 25% of NGM and 60% of TBM has clinical suspicion of malignancy. About 30%
      had radiological suspicion of malignancy. Nearly 62.5% of NGM patients had
      painful swelling and none of tubercular mastitis patients had pain. About 31% of
      NGM patients underwent prior abscess drainage and 40% of TBM patients gave
      history of tuberculosis. Almost 6.25% of NGM and 60% of TBM had axillary
      lymphadenopathy. Cytologically epithelioid cells were identified in 100% of
      patients whereas, granulomas were seen in 62.5% and 80% of NGM and TBM smears
      respectively. Langhans giant cells were frequent among TBM and foreign body giant
      cell among NGM. Caseous necrosis was seen in 60% of TBM and absent in NGM smears.
      CONCLUSION: Though, NGM and TBM is said to have overlapping features, our study
      highlights few clinical and cytological differences which aid in differentiating
      the two entities at primary level. FNAC along with special stain must be
      advocated as the primary tool of diagnosis in cases of GM.

PMID- 28511396
TI  - A Clinicopathological Study of Paediatric Liver Tumours in a Tertiary Care
      Hospital.
AB  - INTRODUCTION: Paediatric primary liver tumours are the third largest group of
      solid abdominal neoplasms in children next to neuroblastoma and Wilms tumour,
      accounting for about 0.5% to 2% of all paediatric neoplasms, in which
      hepatoblastoma is the most common. AIM: The present study was done to estimate
      the incidence of paediatric liver tumours over a period of five years and also,
      to study the clinical behaviour, alpha-fetoprotein correlation and
      histopathological features of paediatric liver tumours. MATERIALS AND METHODS:
      The details of patients treated for paediatric liver tumours for a period of five
      years were retrospectively retrieved from the tumour board and medical records.
      The gross features and all the slides were reviewed and the pathologic diagnosis
      was confirmed and clinicopathological correlation was then done. RESULTS: A total
      of 39 paediatric liver tumours were detected during five years, of which 32 (82%)
      were malignant and seven (18%) were benign with a male to female ratio of 1:1.1.
      Hepatoblastoma was the most common liver tumour accounting for 28 cases (71.8%),
      of which 25 cases (89.4%) were of pure epithelial type. The second most common
      primary tumour was epithelioid haemangioendothelioma with six cases (15.4%) with
      female preponderance, followed by two cases each of hepatocellular carcinoma and
      undifferentiated embryonal sarcoma and one case of hepatocellular adenoma. Serum
      AFP level was increased in hepatoblastoma and in hepatocellular carcinoma, normal
      in hepatocellular adenoma and embryonal sarcoma. Serum AFP level was increased in
      few cases of epithelioid haemangioendothelioma. CONCLUSION: The spectrum of liver
      tumours in children is different from that in the adults. Hepatoblastoma is the
      most common paediatric liver tumour, followed by epithelioid
      haemangioendothelioma. Through better understanding of pathological diagnosis,
      refined surgical staging, newer and more effective radiological techniques and
      standardized multimodal therapies, a substantial number of children diagnosed
      with this highly malignant tumour can expect to survive the disease.

PMID- 28511397
TI  - Fibroadenoma in Axillary Ectopic Breast Tissue Mimicking Lymphadenopathy.
AB  - Swellings in the axilla especially in women are always viewed with suspicion
      owing to a large number of these being associated with breast carcinoma
      presenting as nodal metastasis. In a country like India, tuberculous
      lymphadenopathy is also amongst the first differentials. We present a case of a
      woman with right sided axillary swelling mimicking lymphadenopathy which on Fine
      Needle Aspiration Cytology (FNAC) turned out to be fibroadenoma of the ectopic
      breast tissue. This condition is a rare occurrence in Ectopic Breast Tissue (EBT)
      as opposed to that in the normal breast, the most common pathology affecting
      ectopic breast being carcinomas.

PMID- 28511398
TI  - Undifferentiated Uterine Sarcoma: An Uncommon Case Report.
AB  - Endometrial Stromal Sarcomas (ESS) are rare uterine malignancy of mesodermal
      origin. A 65-year-old female presented with postmenopausal bleeding in the
      Department of Gynaecology in our hospital. Computed Topography (CT) revealed an
      enlarged uterus with areas of low attenuation. On gross appearance endometrial
      cavity was distorted with an irregular friable necrotic mass.
      Histopathologically, it was diagnosed as undifferentiated uterine sarcoma.
      Rhabdoid, osteoid and cartilaginous differentiation were found along with
      osteoclast like giant cells. Immunohistochemistry was strongly positive for CD10.

PMID- 28511399
TI  - Primary Ovarian Endometrioid Stromal Sarcoma Presenting with Infertility.
AB  - Endometrioid Stromal Sarcoma (ESS) is an uncommon tumour that occurs in women
      over wide age range of 11 years to 76 years accounting for only 0.2% of all
      uterine malignancies and for 15%-26% of primary uterine sarcomas. These tumours
      arising from ovary are extremely rare. Most of them are associated with
      nulliparous or perimenopausal women. It is commonly associated with endometriosis
      of the ovary. Here we present this rare case to emphasize on the uniqueness and
      histomorphology of ovarian ESS in patients with endometriosis.

PMID- 28511400
TI  - A Case Report of a Giant Cholesteatoma.
AB  - Cholesteatoma is a well demarcated, non-neoplastic, temporal bone cystic lesion
      with extensive keratinisation. Keratoma and epidermoid cyst are other possibly
      more accurate names suggested to describe the same. It can be classified as
      congenital or acquired. Its management is often complicated by its tendency to
      recidivism/recurrence. Long standing cholesteatomas can be a precursor for
      squamous cell carcinoma. We hereby present a case of giant cholesteatoma in a 45
      year-old female with radiological involvement of the left temporal region,
      periauricular region and infratemporal fossa with lytic destruction of left
      middle ear ossicles, mastoid and squamous part of temporal bone with intracranial
      extension. The enormity of the present lesion along with its bony erosions raised
      the strong clinical suspicion of malignancy. The underlying case report
      highlights the relevance of exhaustive sectioning and immunohistochemistry to
      reach the diagnosis.

PMID- 28511401
TI  - Jejunal Gastric Heterotopia causing Multiple Strictures and Perforation
      Peritonitis- A Case Report with Review of Literature.
AB  - Gastric heterotopias beyond the ligament of Treitz though rare, should be thought
      of in the differential diagnosis of polypoid lesions presenting with
      gastrointestinal bleed or obstructive symptoms especially in children and in the
      young. Here is a 24-year-old male with multifocal jejunal gastric heterotopias
      causing multiple strictures and perforation peritonitis. Patient presented with
      acute abdomen pain and an emergency laparotomy was performed revealing jejunum
      with multiple strictures and perforation, followed by jejunal resection. On gross
      examination polypoid mucosa was noted at the stricture sites which showed
      heterotopic gastric mucosa on microscopy. Jejunal gastric heterotopias are
      extremely rare with less than ten reported cases and those presenting with
      multiple strictures are even rarer. To our knowledge this is the second case of
      jejunal gastric heterotopia presenting with multiple strictures.

PMID- 28511402
TI  - Bladder Adenocarcinoma: A Persisting Diagnostic Dilemma.
AB  - Primary urinary Bladder Adenocarcinoma (PBA) is an uncommon neoplasm and can
      cause diagnostic difficulties due to histologic similarities with adenocarcinomas
      of adjacent structures like Gastrointestinal Tract (GIT) and prostate, since
      involvement of the bladder by metastasis or direct spread can occur. Seven cases
      of bladder adenocarcinomas were diagnosed during a period of four years in a
      tertiary care hospital. Patient's age ranged from 26-78 years with a male
      predilection. Three cases were signet ring type adenocarcinomas, two cases were
      subtyped as enteric variant, one as mucinous variant and one as adenocarcinoma
      Not Otherwise Specified (NOS) variant. One case showed urachal involvement.
      Common site of involvement was the base and posterior wall of the bladder. Three
      cases had prior history of GIT malignancy. No morphologic difference was
      identified to differentiate primary from secondary adenocarcinomas. Bladder
      adenocarcinoma is rare tumours. Primary and secondary adenocarcinomas cannot be
      distinguished from each other on morphologic grounds. Ancillary studies may have
      limited role in distinguishing between the two. Hence, clinical correlation has a
      major role in their evaluation.

PMID- 28511403
TI  - A Prospective Analysis of Drug Interactions in Patients of Intensive Cardiac Care
      Unit.
AB  - INTRODUCTION: Drug-Drug Interaction (DDI) is a serious concern in cardiac
      patients due to polypharmacy. AIM: The present study was aimed to identify the
      potential DDI among hospitalized cardiac patients and evaluate the mechanism and
      severity of such interactions. MATERIALS AND METHODS: A prospective observational
      study was conducted in intensive cardiac care unit of a tertiary care hospital
      for six months. Patients aged 18 years and above and taking two or more drugs
      were included in the study. Medscape drug interaction checker was used to
      identify and analyze the pattern of potential DDI. RESULTS: Out of 500 patients,
      most of the patients were male (78.4%) in the age group of 50-60 years (31%). The
      most common diagnosis was acute coronary syndrome (57.2%). Out of total 2849 DDI,
      2194 (77.01%) were pharmacodynamic, 586 (20.57%) were pharmacokinetic in nature
      while 69 (2.42%) drug pairs interacted by unknown mechanism. Majority of drug
      interactions were significant {2031 (71.29%)} in nature followed by minor
      {725(25.45%)} while serious drug interactions were observed in only 93 (3.26%)
      drug pairs. A positive correlation was observed between patient's age and number
      of drugs prescribed (r=0.178, p<0.001), number of drugs prescribed and potential
      Drug-Drug Interaction (pDDI) (r= 0.788, p<0.001) and between patient's age and
      pDDI (r=0.338, p<0.001). CONCLUSION: The risk of pDDI was more commonly observed
      in elderly male patients particularly with antiplatelet drugs like low dose
      aspirin and clopidogrel.

PMID- 28511404
TI  - Statin Induced Rhabdomyolysis with Non Oliguric Renal Failure: A Rare
      Presentation.
AB  - Statins are safe, well tolerated, efficient and time tested drugs for the
      management of hypercholesterolemia, and thus play a cardinal role in the
      management of patients with heart disease. Although safe in clinical practice,
      they are associated with adverse effects, clinically the most important and most
      severe being muscle related complications/myotoxicity. Rhabdomyolysis, though
      rare, is the most severe form of myotoxicity. The US Food and Drug Administration
      (USFDA) adverse event reporting system reports rate of statin induced
      rhabdomyolysis at 0.3-13.5 cases per 1,000,000 patients. We present a case of a
      74-year-old male who presented with an acute coronary syndrome and was initiated
      on atorvastatin. However, patient developed atorvastatin induced rhabdomyolysis,
      with non oliguric renal failure, which subsequently improved on cessation of
      medication.

PMID- 28511405
TI  - Evaluation of Acute Oral Toxicity of Ethanol Leaves Extract of Catharanthus
      roseus in Wistar Albino Rats.
AB  - INTRODUCTION: Herbal drugs have gained importance globally in the treatment of
      various diseases. Catharanthus roseus is traditionally used as an anti diabetic
      and anti cancer drug. To the best of our knowledge limited data are available on
      acute and sub acute toxicity of C. roseus extract despite its wide spread use in
      traditional medicine. The present study was under taken to evaluate the acute
      oral toxicity of the ethanol leaves extract of C. roseus. AIM: To investigate the
      acute oral toxic effects of ethanol leaves extract of C. roseus. The objective of
      the study was to evaluate organ toxicity related to heart, liver and kidney in
      wistar albino rats. MATERIALS AND METHODS: The experiment was done based on the
      Organization for Economic Co-operation and Development (OECD) guideline 420. The
      study included twenty five non pregnant female wistar rats (n=25). Sighting study
      was done using the fixed dose method. The study was conducted by giving a single
      dose of test drug varying from 5, 50, 300 and 2000 mg and animals were observed
      for fourteen days. Blood samples were collected and biochemical findings SGPT,
      SGOT, urea, creatinine, creatinine phosphokinase and Lactate Dehydrogenase (LDH)
      were analyzed. Food consumption, water intake and histopathology changes were
      evaluated. RESULTS: Catharanthus roseus Extract (CRE) at a dose of 2000 mg did
      not produce mortality. SGOT, SGPT, Creatinine phosphokinase, LDH, urea and
      creatinine were elevated in 300 mg and 2000 mg doses. CONCLUSION: Though there
      was no mortality, the extract of C. roseus higher than 300 mg can produce signs
      of biochemical and histopathological toxicity in liver, kidney and heart. It is
      recommended that lower doses than the studied ones should be used for treatment.

PMID- 28511406
TI  - Effect of Sodium Valproate and Docosahexaenoic Acid on Pain in Rats.
AB  - INTRODUCTION: Analgesics are commonly prescribed medications used to alleviate
      pain of various aetiologies without affecting the patient's consciousness. They
      interfere with the transmission of pain signals. A commonly used antiepileptic
      drug, sodium valproate has been used in various non-epileptic conditions like
      migraine prophylaxis and in the treatment of bipolar disorder because of the
      multiple mechanisms by which it acts. Docosahexanoic Acid (DHA), an omega 3 fatty
      acid, is known to possess analgesic activity. We planned a study to assess the
      effect of sodium valproate alone and in combination with DHA in rat models of
      pain. AIM: To evaluate the analgesic activity of sodium valproate and DHA
      supplementation using various experimental models in albino Wistar rats.
      MATERIALS AND METHODS: For analgesic activity, A total of 48 adult Wistar albino
      rats were divided into eight groups of six rats each. Group I was control (distil
      water 1 ml/kg), Group II received intraperitoneal injection of tramadol (10
      mg/kg), Group III, IV, V were injected intraperitoneal sodium valproate 100, 200,
      400 mg/kg with distil water respectively and Group VI, VII, VIII were given
      sodium valproate 100, 200, 400 mg/kg plus DHA 300 mg/kg (intraperitoneal)
      respectively. Analgesic activity was assessed using hot plate, tail flick and
      acetic acid writhing models. RESULTS: We found that sodium valproate at higher
      doses (400 mg/kg) used either alone along with DHA (300 mg/kg) showed
      statistically significant analgesic activity in comparison to control in various
      experimental models for assessing pain. CONCLUSION: Combination of sodium
      valproate along with DHA has shown promising analgesic activity.

PMID- 28511407
TI  - Gerbode Ventricular Septal Defect -A Rare Cardiac Anomaly Associated with Genetic
      Variants in Indian Population- A Case Series.
AB  - Gerbode defects are rare Ventricular Septal Defects (VSD) constituting
      approximately one percent cases of congenital heart diseases. The genetic
      predispositions towards the Gerbode Defect (GD) have remained an unexplored area
      of study till date. We investigated the genotype-phenotype correlation in
      patients with Gerbode VSD. Molecular genetic study on Sanger sequencing and
      subsequent data analysis showed that the contributing sequence variations in the
      NKX2-5, GATA4 and TBX5 gene lies in one of the highly conserved regions and this
      region is responsible for encoding a functional protein. The resulting genotype
      variation may be responsible for causing the diseased phenotype known as GD.

PMID- 28511408
TI  - Estimation of Total Length of Femur from its Proximal and Distal Segmental
      Measurements of Disarticulated Femur Bones of Nepalese Population using
      Regression Equation Method.
AB  - INTRODUCTION: Length of long bones is taken as an important contributor for
      estimating one of the four elements of forensic anthropology i.e., stature of the
      individual. Since physical characteristics of the individual differ among
      different groups of population, population specific studies are needed for
      estimating the total length of femur from its segment measurements. AIM: Since
      femur is not always recovered intact in forensic cases, it was the aim of this
      study to derive regression equations from measurements of proximal and distal
      fragments in Nepalese population. MATERIALS AND METHODS: A cross-sectional study
      was done among 60 dry femora (30 from each side) without sex determination in
      anthropometry laboratory. Along with maximum femoral length, four proximal and
      four distal segmental measurements were measured following the standard method
      with the help of osteometric board, measuring tape and digital Vernier's caliper.
      Bones with gross defects were excluded from the study. Measured values were
      recorded separately for right and left side. Statistical Package for Social
      Science (SPSS version 11.5) was used for statistical analysis. RESULTS: The value
      of segmental measurements were different between right and left side but
      statistical difference was not significant except for depth of medial condyle
      (p=0.02). All the measurements were positively correlated and found to have
      linear relationship with the femoral length. CONCLUSION: With the help of
      regression equation, femoral length can be calculated from the segmental
      measurements; and then femoral length can be used to calculate the stature of the
      individual. The data collected may contribute in the analysis of forensic bone
      remains in study population.

PMID- 28511409
TI  - Knowledge, Attitude and Practice of Healthcare Managers to Medical Waste
      Management and Occupational Safety Practices: Findings from Southeast Nigeria.
AB  - INTRODUCTION: Awareness of appropriate waste management procedures and
      occupational safety measures is fundamental to achieving a safe work environment,
      and ensuring patient and staff safety. AIM: This study was conducted to assess
      the attitude of healthcare managers to medical waste management and occupational
      safety practices. MATERIALS AND METHODS: This was a cross-sectional study
      conducted among 54 hospital administrators in Ebonyi state. Semi-structured
      questionnaires were used for qualitative data collection and analyzed with SPSS
      statistics for windows (2011), version 20.0 statistical software (Armonk, NY: IBM
      Corp). RESULTS: Two-fifth (40%) of healthcare managers had received training on
      medical waste management and occupational safety. Standard operating procedure of
      waste disposal was practiced by only one hospital (1.9%), while 98.1% (53/54)
      practiced indiscriminate waste disposal. Injection safety boxes were widely
      available in all health facilities, nevertheless, the use of incinerators and
      waste treatment was practiced by 1.9% (1/54) facility. However, 40.7% (22/54) and
      59.3% (32/54) of respondents trained their staff and organize safety orientation
      courses respectively. Staff insurance cover was offered by just one hospital
      (1.9%), while none of the hospitals had compensation package for occupational
      hazard victims. Over half (55.6%; 30/54) of the respondents provided both
      personal protective equipment and post exposure prophylaxis for HIV. CONCLUSION:
      There was high level of non-compliance to standard medical waste management
      procedures, and lack of training on occupational safety measures. Relevant
      regulating agencies should step up efforts at monitoring and regulation of
      healthcare activities and ensure staff training on safe handling and disposal of
      hospital waste.

PMID- 28511412
TI  - Regulation of Molecular Diagnostic (NAT) Kits For HBV, HCV and HIV in India.

PMID- 28511410
TI  - Preventive Training among Medical Interns in Mexico City and Its Association with
      Needlestick and Sharp Injuries - A Cross Sectional Study.
AB  - INTRODUCTION: Medical students are a vulnerable group for the acquisition of
      blood borne pathogens due to their lack of experience. In Europe and Asia
      preventive training programs have reduced accidental exposures. AIM: The aim of
      the study was to compare the lifetime prevalence of Needlestick and Sharp Objects
      Injuries (NSIs) among medical interns who received preventive training versus
      those without such training in Mexico City. MATERIALS AND METHODS: In 2013, a
      cross-sectional study was performed applying an anonymous self-administrated
      questionnaire. The study population included 467 medical students, male and
      female, at the end of their internship. The lifetime prevalence of NSI was
      estimated and compared between students who had received preventive training and
      those who did not. RESULTS: The overall lifetime prevalence of NSI was 58%.
      Lifetime prevalence was higher in students without preventive training compared
      to those who had such a training (68% vs 51%; p value= 0.002). NSI Lifetime
      prevalence was not associated with sex, age or place of birth. The task most
      commonly associated with the latest NSI in trained and untrained students was
      withdrawing blood. CONCLUSION: NSI are frequent accidents among medical students
      in Mexico City, especially during blood taking. Training units on how to prevent
      NSI should be encouraged in Mexican medical colleges.

PMID- 28511411
TI  - Relationship of Lifestyle with Academic Achievement in Nursing Students.
AB  - INTRODUCTION: A healthy lifestyle is one of the main factor in maintaining the
      health of people in society. With regard to the role of youth and students in
      public health, they must complete and follow a training program on lifestyle
      related factors. One of the main aim of the training centres is to improve the
      academic achievement of students. AIM: This study was designed to determine the
      correlation of lifestyle with academic achievement in nursing students. MATERIALS
      AND METHODS: This was a cross-sectional study, wherein all nursing students of
      School of Borujen Nursing were selected by census sampling. Data gathering tool
      was Walker's lifestyle questionnaire which was modified for the purpose of the
      study. To evaluate the educational status of students, final grade point average
      was considered as an indicator of academic achievement. To analyze the data, SPSS
      version 16.0, and descriptive and analytical tests were used. RESULTS: The
      results indicated that most subjects (61.01%) displayed moderate levels of
      lifestyle. Pearson's correlation coefficient showed the significant positive
      relationship between lifestyle and academic achievement (p=0.03 and r=0.628).
      CONCLUSION: To improve the academic achievement of students, in addition to the
      cognitive abilities-perception, their lifestyle should also be considered.
      Therefore, it is suggested to incorporate lifestyle education in the curriculum
      of nursing students so as to improve their lifestyle.

PMID- 28511413
TI  - Knowledge Attitude and Perception of Sex Education among School Going Adolescents
      in Ambala District, Haryana, India: A Cross-Sectional Study.
AB  - INTRODUCTION: Adolescence is a highly dynamic period characterised by rapid
      growth and development. Adolescents have limited knowledge about sexual and
      reproduction health, and know little about the natural processes of puberty,
      sexual health, pregnancy or reproduction. Sex education should be an integral
      part of the learning process beginning in childhood and continuing into adult
      life, because it is lifelong process. AIM: This study was carried out to identify
      the knowledge and attitude of imparting sex education in school going adolescents
      in rural and urban area of Ambala district. MATERIALS AND METHODS: A cross
      sectional study design was used to study the knowledge of reproductive and sexual
      health among school going children. A total of 743 adolescents from age group of
      13-19 year were studied, using self designed semi-structured questionnaire to
      assess the knowledge regarding reproductive and sexual health among adolescents.
      RESULTS: The mean age of study subjects was 15.958+/-1.61 years, majority of
      adolescents i.e., 93.5% favour sex education. An 86.3% said sex education can
      prevent the occurrence of AIDS and 91.5% of adolescents prefer doctors should
      give them sex education followed by 83.0% school/teacher and least preference was
      parents 37.3%. CONCLUSION: There were substantial lacunae in the knowledge about
      reproductive and sexual health. Students felt that sex education is necessary and
      should be introduced in the school curriculum.

PMID- 28511414
TI  - A Community Based Study on Pelvic Inflammatory Disease in Postmenopausal Females:
      Microbiological Spectrum and Socio-Demographic Correlates.
AB  - INTRODUCTION: Pelvic Inflammatory Disease (PID) is a common and serious
      complication of sexually transmitted diseases in young women but is rarely
      diagnosed in the postmenopausal women. Very few studies have been done regarding
      post-menopausal PID. AIM: To determine the burden of PID, associated micro
      organisms, pathophysiology and risk factors among post-menopausal women of the
      community. MATERIALS AND METHODS: A cross-sectional study was conducted among 530
      post-menopausal women in the registered field practice areas of the JN Medical
      College and Hospital, Aligarh, Uttar Pradesh, India. A pre designed and pre
      tested proforma was used to obtain data regarding socio-demographic details and
      factors associated with PID. Clinical and laboratory examinations were done to
      confirm the diagnosis of PID. Data was analyzed using SPSS 23.0. Association
      between categorical variables was tested with chi-square test and logistic
      regression analysis was used to find independent risk factors. The value of
      p<0.05 was considered as significant. RESULTS: About 11.55% of the study subjects
      were diagnosed with PID (12.5% in rural areas and 10.6% in urban areas).
      Bacterial vaginosis followed by Trichomonas vaginalis were most common. Among the
      important risk factors, significant association was found with occupation of the
      women, increasing parity, multiple sexual contacts, and associated pelvic organ
      prolapse. Association with smoking, chronic illnesses, diabetes mellitus and
      hypertension, and associated urinary tract infection were not found to be
      significant. CONCLUSION: The study shows the hidden burden of the disease in the
      community and the associated risk factors, which can be prevented by life style
      and cultural changes if incorporated earlier in the lives.

PMID- 28511415
TI  - Impact of a Structured Tuberculosis Awareness Strategy on the Knowledge and
      Behaviour of the Families in a Slum Area in Chhattisgarh, India.
AB  - INTRODUCTION: Of different methods of disease prevention, health education and
      awareness programmes can empower people regarding several aspects of disease
      management and thereby enabling them in accessing the right treatment, in right
      time, at right place. AIM: The aim of this study was to assess the impact of a
      structured Tuberculosis (TB) awareness strategy on the knowledge and behaviour of
      slum dwellers of Durg, Chhattisgarh, India. MATERIALS AND METHODS: A TB awareness
      intervention was implemented in terms of informing the houses of marginalized and
      vulnerable communities about TB, its symptoms, diagnosis, treatment and Revised
      National TB Control Program (RNTCP) services and the impact of the same was
      assessed through a survey questionnaire before and after the implementation of
      the intervention. RESULTS: Of the knowledge components the improvement was
      incurred above 90% among the study participants in all components except in two
      components such as; modes of TB transmission and availability of free treatment
      facilities. In the behavioural segment, after the implementation of the awareness
      strategy, 53% and 92% of the respondents reported to visit government health
      facility for seeking help for their general and TB related problems respectively.
      Similarly the responses regarding not approaching the government health facility
      for TB care were changed after the implementation of the awareness strategy and
      36% of the respondents said they would prefer to visit government health facility
      for TB care. CONCLUSION: Health education activities should be directed to
      improve the knowledge of slum dwellers regarding the modes of TB transmission and
      availability of free treatment at public health facilities.

PMID- 28511416
TI  - Correlation of Cotinine Levels with Use of Smokeless Tobacco (Mishri) among
      Pregnant Women and Anthropometry of Newborn.
AB  - INTRODUCTION: 'Smokeless tobacco' is the term used for the tobacco that is
      consumed in un-burnt form and it can be used orally or nasally. Cotinine, a
      nicotine metabolite, is used to quantify exposure to tobacco, which readily gains
      access to foetal circulation. Cotinine is invariably found in coelomic, amniotic
      and foetal serum when maternal serum cotinine levels exceed 25ng/ml. AIM: To
      estimate cotinine levels among pregnant women using and not using smokeless
      tobacco (mishri) and to correlate cotinine level with anthropometry of newborns.
      MATERIALS AND METHODS: A hospital based cohort study was conducted at Krishna
      Hospital, Karad, District Satara, Maharashtra, India. Pregnant women who were
      using smokeless tobacco (mishri) during pregnancy were analyzed for cotinine
      levels in blood by using ELISA kit tech and correlated with anthropometry of
      newborn babies and compared with non users of tobacco. RESULTS: About 480 gm
      reduction in Birth weight and 6.5 cm reduction in birth length of babies born to
      mishri users compared to non users of tobacco and also cotinine levels among
      users were found significantly negatively correlating with anthropometric
      measurement of newborn babies. CONCLUSION: A pro-active effort is essential to
      educate the women about adverse effects of tobacco in general and on the
      intrauterine growth of the baby in particular.

PMID- 28511417
TI  - Effectiveness of A Four-Week Diet Regimen, Exercise and Psychological
      Intervention for Weight Loss.
AB  - INTRODUCTION: Obesity is accompanied by restriction in the quality of life and an
      increased risk of morbidity and mortality. Cardiovascular, orthopedic, and
      metabolic disorders are among the possible consequences. In the management of
      obesity, a combination therapy that includes dietary, exercise, and behaviour
      modules has proven its worth. AIM: To evaluate the effect of weight-associated
      parameters, circulation associated parameters, glucose metabolism, body
      composition and life quality changes within a four-week inpatient rehabilitation
      program. MATERIALS AND METHODS: Fifty-two patients underwent a 4-week inpatient
      rehabilitation program consisting of nutrition therapy, behavioural therapy and
      exercise therapy modules at the Eleonoren Clinic of Winterkasten, Germany.
      RESULTS: The mean weight reduction of 52 obese patients 40 (76.9%) males, 12
      (23.1%) females; mean age 46 years; mean Body Mass Index (BMI) 43,79 kg/m2)
      achieved was 7.1 kg (from 1.20 kg to 17.50 kg), and the BMI reduction was 2.3
      kg/m2 (from 0.40 kg/m2 to 5.40 kg/m2). The excessive weight loss was highly
      significant (p<0.001). Weight reduction was accompanied by an improvement in the
      diabetic metabolic state (lowering of fasting blood-glucose 20 mg/dl,
      postprandial blood glucose 26 mg/dl, HbA1c 0.27%). In all 73% of the patients
      suffered from arterial hypertonia. The significant mean decline of systolic and
      diastolic blood pressure was 12.8 mmHg and 6.8 mmHg, respectively. The resting
      pulse was reduced by an average of 11 beats per minute. The Bioelectric Impedance
      Analysis (BIA) revealed a significant reduction of body fat content (p<0.001).
      The subjective impression of impaired life quality (SF-36 questionnaire) improved
      significantly. CONCLUSION: The study clearly shows that the inpatient
      rehabilitation program at the Eleonoren Clinic was suitable to enhance the
      physical and mental state of people with obesity. In a two-year follow-up program
      the patients should take care of a permanent lifestyle change toward an improved
      dietary, movement and health behaviour.

PMID- 28511418
TI  - Screening in Public Health and Clinical Care: Similarities and Differences in
      Definitions, Types, and Aims - A Systematic Review.
AB  - INTRODUCTION: The concept of screening can be many times misleading to many
      people. This may be partly due to the way screening is described and explained in
      textbooks and journal articles. AIM: To review prominent public health and
      epidemiology textbooks, dictionaries, and relevant journal publications for
      definitions and examples of screening, with the aim of identifying common usages
      and concepts, as well as sources of potential confusion. MATERIALS AND METHODS:
      Commonly available epidemiology and public health textbooks and peer reviewed
      journals were searched for definitions and examples of screening. The search
      located seven journal articles, 10 textbooks, and one dictionary. The search
      platforms used were Pubmed, BIOSIS, EMBASE, Medline-OVID and Scopus under the
      Epidemiology and Biostatics subject head listed with Life Sciences. RESULTS:
      Descriptions of screening give varying emphasis to whether it is a test or a
      program, the aims of screening, the setting in which it is conducted, eligibility
      criteria, who initiates and who is intended to benefit and whether the condition
      being screened is an infectious or chronic disease or a risk-elevated state. Four
      essentially different 'types' of screening are described, using seven terms and
      occasionally contradictory examples. The detection of asymptomatic infectious
      cases is gradually changing from screening to surveillance as part of infection
      control. CONCLUSION: Voluntary screening programs rely on high participation to
      be effective and support and trust of the public are essential for the continued
      success of the public health profession. Consistent terminology is important for
      patients, providers and policymakers to understand what screening is and is not.
      Clear definitions are needed if we are to evaluate and communicate the risks and
      benefits of screening in public health.

PMID- 28511419
TI  - Nasal NK/T Cell Lymphoma Presenting with Perforation of Palate: A Case Report and
      Review of Literature.
AB  - Nasal Natural Killer (NK)/T cell lymphoma, commonly mentioned in the literature
      as Lethal Midline Granuloma (LMG) is an unusual pathology of the oro-maxillo
      facial region characterized by aggressive and progressive destruction of the
      face, nose, palate and pharynx. This disease is now classified as a T-cell
      lymphoma based on modern cytogenetics, immunologic and molecular studies.
      However, it is mentioned in various literatures by various names. Here, we
      present one such clinically diagnosed, histopathologically and immunologically
      confirmed case of LMG, designated as NK/T cell lymphoma in a 56-year-old male.
      The uncommon presentation of NK/T cell lymphomas should be kept as a differential
      diagnosis for management of patients.

PMID- 28511420
TI  - Effect of Intraperitoneal Injection of Saffron on the Treatment of Experimental
      Endotoxin Induced Uveitis in the Rabbit.
AB  - INTRODUCTION: Saffron with scientific name of "Crocus sativus" from the family
      "Iridaceae" is a plant without stem and root. Antioxidative and immunomodulatory
      effects of saffron has been demonstrated in different studies. AIM: To assess the
      effects of saffron in the treatment on Lipopolysaccharide (LPS) induced uveitis
      in the rabbit. MATERIALS AND METHODS: Thirty healthy female New Zealand white
      rabbits were prepared. LPS induced uveitis was confirmed via slit lamp
      examination 24 hours after intravitreal injection of Salmonella typhimurium LPS
      endotoxin in the right eye of all rabbits. Then the animals were randomly divided
      into two equal groups - group 1 (controls) and group 2 (saffron). After 24 hours
      of intravitreal injection of LPS, 60 mg/body weight of saffron was injected
      intraperitoneally for Group 2. On the seventh day after intraperitoneal
      injection, all rabbits of both groups were euthanized with an overdose
      intraperitoneal injection of sodium thiopental. Immediately after euthanasia,
      enucleation of both groups of rabbits was done. Clinical Scoring System (CSS) and
      pathological severity score of uveitis was assessed for each eye. RESULTS: No
      statistical difference in the CSS was found in days 3,5, and 7 after
      intraperitoneal injection of saffron. Also, Pathological Severity Score (PSS) did
      not show a significant difference between two groups. Additionally, the maximum
      PSS of both groups was very closed but the number was observed in the saffron
      group (20%) more than control group (10%). CONCLUSION: Intraperitoneal injection
      of saffron was ineffective in the management of experimental uveitis. Further
      studies with different dosages and follow up and using other routes of
      administration are needed.

PMID- 28511421
TI  - Surgical Outcome of Epicanthus and Telecanthus Correction by Double Z-Plasty and
      Trans-Nasal Fixation with Prolene Suture in Blepharophimosis Syndrome.
AB  - INTRODUCTION: Blepharophimosis Syndrome (BPES) is a complex and rare disease
      characterized by epicanthus inversus, telecanthus, lateral ectropion, narrowed or
      shortened inter-palpebral fissure distance and ptosis. It is mostly bilateral and
      may or may not be symmetrical. It is typically inherited as an autosomal dominant
      trait. In sporadic cases, the disease may occur without a prior family history as
      a genetic mutation from a deletion or translocation of the FOXL2 gene, which maps
      to chromosome 3q23. Surgical treatment of this disease poses an oculoplastic
      challenge due to multiple complex eyelid deformities. AIM: To evaluate the
      functional and cosmetic outcome of telecanthus and epicanthus correction by a
      Mustarde's rectangular double Z-Plasty and trans-nasal fixation using 1-0 prolene
      suture in BPES. MATERIALS AND METHODS: This was prospective, interventional study
      of 16 patients over a period of three years. In this study, all patients had BPES
      with prominent epicanthus and telecanthus. Mustarde's double Z-plasty and trans
      nasal fixation with 1-0 prolene suture was performed in the first of a two-stage
      operation. If ectropion was present, the lateral ectropion was corrected by a
      base-out flap transfer from the upper eyelid to the lower eyelid. After three
      months, a 2nd stage was undertaken, involving a lateral canthoplasty for
      horizontal widening of a short palpebral fissure and a tarso frontalis sling with
      silicone rod for correction of moderate to severe ptosis. Patients were followed
      up for six months to one year with postoperative ophthalmologic examinations and
      photographs. RESULTS: Out of 16 patients, 10 were females and six were males. All
      the patients had bilateral involvement. In this study preoperative Inner
      Intercanthal Distance (IICD) ranged from 38 mm to 42 mm and the mean IICD was
      41.2+/-0.57 mm. Postoperative IICD ranged from 31 mm to 34 mm. Horizontal
      Palpebral Fissure Length (HPFL) ranged from 20 mm to 23 mm and the mean value of
      HPFL was 21.50 mm preoperatively. Postoperative HPFL ranged from 26 mm to 29 mm
      and had a mean value of 28.50 mm, which was much improved after a combined
      correction of telecanthus and lateral canthoplasty. The mean preoperative IICD
      and HPFL ratio was 1.77 and was reduced to a postoperative value of 1.2. The
      Marginal Reflex Distance1 (MRD-1) test value improved from +1.25 mm to +3.50 mm
      postoperatively after placement of a tarsofrontalis sling with silicone rod using
      the Fox's Pentagon technique. In this study, two eyes had minimal unequal
      correction but were cosmetically and functionally acceptable. Correction of IICD
      is possible up to 6 mm. No major complication e.g., CSF rhinorrhea was noted in
      this series and preoperative prominent epicanthal folds were abolished.
      CONCLUSION: Here we propose a two-staged procedure involving a combined
      Mustarde's double Z-plasty with transnasal fixation using a 1-0 prolene suture
      with a flap transfer from the upper lid to the lower lid in the first stage and a
      lateral canthoplasty with a tarsofrontalis sling and silicone rod in the second
      stage. This technique is effective to correct epicanthus, telecanthus, ptosis and
      lateral ectropion in BPES with good cosmetic and functional outcome.

PMID- 28511422
TI  - Posterior Chamber Scleral Fixation of Intraocular Lenses in Post-Vitrectomised
      Aphakic Eyes.
AB  - INTRODUCTION: The best method of aphakia correction is in the bag implantation of
      Posterior Chamber Intraocular Lens (PCIOL). When this ideal procedure is not
      possible due to lack of integrity of posterior capsule or zonules, the other
      alternatives are broadly categorized into two: extraocular and intraocular.
      Whereas, the former includes contact lenses and aphakic glasses, the latter ones
      are further divided into anterior and posterior chamber methods. Anterior Chamber
      Intraocular Lenses (ACIOL) can be with or without iris claw. At the posterior
      chamber, fixation of the lenses can be with glue or sutures. When there is
      combined Pars Plana Vitrectomy (PPV) and lensectomy or if the indication of PPV
      is dropped nucleus or intraocular lens, a modality of aphakia correction should
      be devised. Posterior Chamber Scleral Fixation of Intraocular Lenses (PCSFIOL)
      with sutures is a preferred method because of its low complication profile.
      However, data on correction of aphakia after combined PPV and lensectomy is
      limited. To fill in this gap in knowledge, we evaluated the secondary PCSFIOL in
      aphakic eyes after previous PPV and lensectomy. AIM: To assess the outcome and
      complication profile of a large series of patients who underwent secondary
      PCSFIOL implantation with sutures after combined PPV and lensectomy. MATERIALS
      AND METHODS: Records of all patients who had undergone secondary PCSFIOL
      implantation with sutures after combined PPV and lensectomy from 2010 to 2014
      were reviewed retrospectively for visual outcomes and complications. Patients'
      demographic data, indication for PPV, best corrected preoperative and
      postoperative visual acuities, complications of surgery, and indications of
      PCSFIOL and length of follow up were collected and analyzed. RESULTS: A total of
      148 eyes of 148 patients (127 males and 21 females) were identified. Mean age at
      surgery was 32.5+/-8 years (range 2.5-73 years) with a mean follow up 23+/-14
      months (range 3-114 months). A total of 95.27%, 2.70% and 2.02% of patients had
      improvement, maintenance and worsening of their final postoperative visual
      acuities respectively. A total of 32 (21.62%) of 148 eyes had postoperative
      complications from PCSFIOL with Epiretinal Membrane (ERM) formation being the
      most common. They all required one form of management or the other. Suture
      breakage leading to PCSFIOL subluxation or dislocation occurred in four eyes
      (2.70%). CONCLUSION: PCSFIOL with sutures is a preferred method in the management
      of post-vitrectomised aphakic eyes when the capsular or zonular support is not
      adequate for in the bag implantation of posterior chamber intraocular lenses.

PMID- 28511423
TI  - Bardet Biedl Syndrome - A Report of Two Cases with Otolaryngologic Symptoms.
AB  - Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder characterized
      primarily by rod-cone dystrophy, postaxial polydactyly, central obesity, mental
      retardation, hypogonadism, and renal dysfunction. We present two cases of this
      syndrome, both female, who presented with complaints of nyctalopia and mental
      retardation, and additionally one of them had sensorineural hearing loss while
      the other had serous otitis media. Hearing loss being a rare presentation is
      worth reporting. Both the patients were given a course of vitamin A and the
      parents were counseled regarding the prognosis and additional complications
      associated with the syndrome.

PMID- 28511424
TI  - Mechanism and Immediate Outcome of Significant Mitral Regurgitation Following
      Balloon Mitral Valvuloplasty with JOMIVA Balloon.
AB  - INTRODUCTION: Balloon Mitral Valvuloplasty (BMV) with inoue balloon is the most
      common technique being followed worldwide. Over the wire BMV is a modified
      technique with Joseph Mitral Valvuloplasty (JOMIVA) balloon and is being followed
      in certain centres. We hypothesized that, the incidence and mechanism of Mitral
      Regurgitation (MR) is likely to be different from that of inoue balloon. AIM: To
      assess the mechanism and immediate clinical outcome of significant MR following
      BMV with JOMIVA balloon retrospectively. MATERIALS AND METHODS: We
      retrospectively analyzed the outcome of 48 patients who developed moderate to
      severe MR out of 249 patients who underwent BMV in our institute. We analyzed the
      echocardiographic and clinical parameters of these patients. RESULTS: Nineteen
      (7.6%) patients developed severe MR and 29 (11.2%) patients developed moderate
      MR. Commisural separation resulting in MR was the most common cause which was
      contributing to 73.6 % and 85.7% of patients with moderate and severe MR
      respectively. Leaflet tear was the second most common cause which contributed to
      15.7% and 14.2% of patients with severe and moderate MR respectively. Chordal
      rupture contributed to 10.5% of patients with severe MR. Six (31.6%) patients
      with severe MR developed worsening breathlessness among them one had to be
      referred for mitral valve replacement during index hospitalization and the rest
      could be managed medically. Patients with moderate MR remained asymptomatic and
      stable. CONCLUSION: Severe MR following JOMIVA BMV results most commonly due to
      wide separation of commisures. JOMIVA balloon is less likely to cause damage to
      subvalvular structures than inoue balloon. Most patients who develop severe MR
      will not require emergency mitral valve replacement. Moderate MR is well
      tolerated clinically.

PMID- 28511425
TI  - Early Experience of Sofosbuvir based Combination Therapy in "Real-Life" Cohort
      with Chronic Hepatitis-C Infection.
AB  - INTRODUCTION: There is scarcity of data in literature regarding the treatment
      response with Sofosbuvir (SOF) based therapy in Indian patients with chronic
      Hepatitis-C Virus (HCV) infection. AIM: This study was designed to observe
      initial treatment response to SOF based therapy in a "real-life" cohort of Indian
      patients with HCV infection. MATERIALS AND METHODS: This is a prospective,
      observational and single center study. A total of 107 patients who were diagnosed
      with chronic HCV infection and received SOF based treatment between March 2015
      and December 2015 were included. The patients were treated with either triple
      drug regimen [SOF, Ribavirin (RBV) and Pegylated Interferon-alpha (Peg IFN
      alpha)] or dual drug regimen (SOF and RBV) for either 12 or 24 weeks. The
      virological responses were obtained at baseline and thereafter weekly (up to four
      weeks) till viral load became undetected during treatment. RESULTS: A total of
      107 patients who received SOF based therapy for chronic HCV infection were
      included in the study. Mean age of the patients was 48.7+/-10.7 years. Among
      included patients, 24 (22.4%) patients were treatment-experienced. Majority of
      the patients (n=69; 64.5%) were infected with HCV genotype-3. Except one patient,
      all the included patients achieved virological response up to week-4 of the
      treatment. There was statistically insignificant association between virological
      response (up to four week of the treatment) and severity of the disease
      (cirrhosis and non-cirrhosis) or treatment status (treatment-naive and treatment
      experienced), or HCV genotype (genotype-1 and 3). CONCLUSION: The results of this
      observational study demonstrated rapid initial virological response of SOF based
      therapy in "real-life" cohort of Indian patients with chronic HCV infection.
      However, long-term follow-up data are needed to ensure the sustained antiviral
      efficacy of SOF based therapy.

PMID- 28511426
TI  - Effect of Anti-Cyclic Citrullinated Peptide and HLA-DRB1 Subtypes on Clinical
      Disease Activity Index in Rheumatoid Arthritis Patients.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a crippling disease with a global
      prevalence of approximately 0.5%-1% in adults. Genetic, environmental and
      immunologic factors contribute importantly to pathogenesis of RA. American
      College of Rheumatology (ACR) assists in early diagnosis of the disease. AIM: The
      aim of this study was to investigate the effects of HLA-DRB1 gene and anti-Cyclic
      Citrullinated Peptide (CCP) antibody on Clinical Disease Activity Index (CDAI)
      and to determine the frequency of HLA-DRB1 alleles in the patients with RA.
      MATERIALS AND METHODS: In this descriptive-analytical study, 64 patients with RA
      referring rheumatology clinic of Hajar Hospital, Shahr-e-Kord, Iran were enrolled
      based on ACR criteria (1987) by convenience sampling. All patients were examined
      to assess primary CDAI and referred to laboratory for serologic tests [Rheumatoid
      Factor (RF) and anti-CCP]. After the patients' DNA was extracted, HLA-DRB1 was
      determined per single specific primer-polymerase chain reaction by inno-train
      kits. The patients were re-examined six months later. RESULTS: The most prevalent
      type of HLA-DRB1 in the studied patients was 04. In patients with HLA-DRB1 (04),
      HLA-DRB1 (01), and HLA-DRB1 (15), CDAI decreased pronouncedly after six months,
      but in other patients it did not (p<0.05). Of the patients, 81.3% had high titers
      of anti-CCP, but no association between anti-CCP and CDAI was found. CONCLUSION:
      RA could be a multifactorial disease. The patients with HLA-DRB1 (04), HLA-DRB1
      (01) and HLA-DRB1 (15) showed a good response to routine treatments. The patients
      with HLA-DRB1 (04) are likely to have no decrease in secondary CDAI. High titers
      of anti-CCP in patients may indicate the severity of RA in the studied region and
      perhaps environmental, genetic and unknown or idiopathic factors are
      aetiologically crucial.

PMID- 28511427
TI  - Role of Omega-3 Fatty Acids on Lipid Profile in Diabetic Dyslipidaemia: Single
      Blind, Randomised Clinical Trial.
AB  - INTRODUCTION: Diabetic dyslipidaemia is characterised by hypertriglyceridaemia,
      low High Density Lipoprotein (HDL), postprandial lipimea, small and dense LDL
      particles is considered to be a major predisposing factor for various
      macrovascular complications. Omega-3 fatty acids are fish oil derivative
      introduced in the market for dyslipidaemia associated with increased triglyceride
      level. AIM: To study the effect of omega-3 fatty acids on lipid profile in Type
      II diabetes patients. MATERIALS AND METHODS: This study was prospective, single
      blind, randomized comparative trial. Hundred patients were randomized into three
      groups. Group I received metformin 500 mg twice daily and placebo, Group II
      received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) once daily
      and the Group III received metformin 500 mg twice daily and omega-3 fatty acids
      (1 gram) twice daily. ANOVA test was applied for analysis. RESULTS: Group II was
      effective in reducing the triglyceride level from 144.59+/-14.18 mg/dl to 101+/
      13.31 mg/dl which was significant as compared to Group I from 147.67+/-18.57
      mg/dl to 145.8+/-19.86 mg/dl respectively. Group III containing 1 g of omega-3
      fatty acids twice daily showed decrease from 144.83+/-22.17 mg/dl to 86+/-17.46
      mg/dl and was more effective in reducing triglyceride levels than Group II
      containing 1 gram of omega-3 fatty acids once daily. CONCLUSION: Omega-3 fatty
      acids can be given in conjunction with metformin to reduce triglyceride levels in
      diabetic dyslipidaemia without any adverse drug reactions or any drug
      interaction. Omega-3 fatty acids were effective in reducing the triglyceride
      level significantly as compared to placebo. Two grams of omega-3 fatty acids were
      more effective than 1 gram of omega-3 fatty acids in reducing triglyceride
      levels.

PMID- 28511428
TI  - Incidence of Metabolic Syndrome in Patients Admitted to Medical Wards with ST
      Elevation Myocardial Infarction.
AB  - INTRODUCTION: Metabolic Syndrome (MS) consists of a cluster of metabolic
      abnormalities that confer exaggerated risk of cardiovascular disease. MS is a
      novel risk factor for Coronary Artery Disease (CAD) and is a rising disease
      entity in Asia. Incidence of ST Elevation Myocardial Infarction (STEMI) is high
      in patients with MS. There is limited data on prevalence of MS in patients with
      Acute Myocardial Infarction (AMI). AIM: To determine frequency of MS in patients
      admitted with STEMI. MATERIALS AND METHODS: Hundred Consecutive patients between
      25 to 75 years who were admitted with STEMI at Govt medical college Thrissur were
      included in this prospective study. Subjects were assessed for five-component
      conditions of metabolic syndrome. Criteria to identify MS were based on a
      "Consensus statement for diagnosis of metabolic syndrome for Asian Indians".
      Presence of three or more of following suggest MS, Waist Circumference (WC)>90 cm
      in men and 80 cm in women, Blood pressure >130/85 mm Hg, Fasting Plasma Glucose
      (FPG) >100 mg%, serum triglycerides >150 mg/dl, High Density Lipoprotein (HDL)<40
      mg/dl in male and<50 mg/dl in female. Statistical analysis was performed using
      Epi-Info software. Data expressed as numbers and percents were compared by Chi
      square test. RESULTS: Study enrolled 100 patients (males 80, females 20) with a
      mean age of 58. Frequency of MS in patients with STEMI was 40% (36% of males and
      55% of females). Prevalence of components in the MS group was WC >80/90 -31(71%),
      BP>130/85- 23(58%), FPG >100 - 37(93%), HDL <40 (male)/ 50 (female) - 18(45%), TG
      >150 -15(37.5%). CONCLUSION: The present study concluded that there is a
      remarkably high occurrence of metabolic syndrome and central obesity in patients
      with ST elevation Myocardial Infarction (MI) in our local population especially
      in females. Considering this fact the role of specific and targeted intervention
      for clinical detection and management of MS including lifestyle modifications
      needs to be addressed.

PMID- 28511429
TI  - An Assessment of Osteoporotic Conditions among Users and Non-Users of Warfarin: A
      Case-Control Study.
AB  - INTRODUCTION: Warfarin is an oral anticoagulant which is associated with a
      decrease in Bone Mass Density (BMD). AIM: The study aimed to explore the
      prevalence of osteoporosis conditions in Malaysians with chronic warfarin
      patients using calcaneal quarter of Quantitative Ultrasound (QUS) machine and to
      investigate whether long-term sodium warfarin therapy that antagonizes vitamin K
      is affecting the increasing rate of osteoporosis in Penang and to find the risk
      factors of getting osteoporosis among warfarin users and its non users. MATERIALS
      AND METHODS: A case-control study was conducted among 130 patients using
      warfarin, attending the outpatient clinic at Hospital Pulau Pinang. A convenience
      sampling method was used to recruit the required sample. Another 140 subjects
      were selected from the community as a control group (non-users of warfarin).
      RESULTS: This study showed that more than three-quarter patients (82%) were at
      high risk of abnormal BMD. The warfarin users were two times more likely to have
      a higher osteoporosis risk compared to control group. Moreover, BMD has a
      negative correlation with age, but has a positive correlation with Body Mass
      Index (BMI). Patients showed a negative correlation with a higher dose of
      warfarin intake. CONCLUSION: This study concluded that osteopenia and
      osteoporosis are serious problems between users and non-users warfarin in Penang.
      Therefore, it should be taken into consideration in the Malaysian Health
      Ministry's agenda.

PMID- 28511430
TI  - Study on the Relation between Colorectal Cancer and Gall Bladder Disease.
AB  - INTRODUCTION: Colorectal cancer is cancer of the large intestine, the lower part
      of digestive system which includes the sigmoid colon and rectum. AIM: To study
      the relation of incidence of colorectal cancer with previous gall bladder disease
      or post-cholecystectomy status, a relation between gall bladder disease and
      smoking in particular and the most common region of colon involved in colorectal
      cancer in gall bladder disease and non-gall bladder disease patients. MATERIALS
      AND METHODS: A total of 256 patients with symptoms of rectal bleeding, change in
      bowel habit, unexplained tiredness, weight loss, pelvic pain, jaundice and
      abdominal distension were screened by using colonoscopy among whom 30 patients
      were diagnosed with colorectal cancer. Detailed history was taken with the help
      of a modified questionnaire and the patients were assessed, examined and the list
      of investigations such as faecal occult blood test, ultrasound of abdomen and
      pelvis, colonoscopy, sigmoidoscopy, barium enema, Computed Tomography (CT),
      Magnetic Resonance Imaging (MRI) of the abdomen and pelvis, tumour markers like
      Carcinoembryonic Antigen (CEA) and biopsy were collected. Patient pool was
      categorized into Gall Bladder Disease (GBD) and Non Gall Bladder Disease (NGBD).
      Proportions test and Fisher's-Exact test were used to calculate the p-values.
      RESULTS: Ten patients had previous gall bladder disease (33%) which was
      significant with a p-value of 0.016 by proportions test. Two patients underwent
      cholecystectomy, two patients underwent Endoscopic Retrograde Cholangio
      Pancreatography (ERCP) and the remaining six patients did not take any treatment
      for their gall bladder disease. Five patients with previous gall bladder disease
      were found to be smokers with a p-value of 0.091. The average age was 47.2 years
      in males and 42.2 years in females. Males constituted 66.6% (20 males) of the
      diseased population whereas, females constituted 33.4% (10 females). Rectal
      bleeding and altered bowel habits were the commonest symptoms. Confirmation of
      the disease was proven using CT abdomen and biopsy. Right sided colorectal cancer
      was common in GBD patients. Left sided colon cancer was common in NGBD patients.
      CONCLUSION: This study established a statistically significant risk of colorectal
      cancer following cholelithiasis though no risk was apparent following
      cholecystectomy.

PMID- 28511431
TI  - The Relationship between Serum Level of Vitamin D3 and the Severity of New Onset
      Rheumatoid Arthritis Activity.
AB  - INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic inflammatory disease which
      typically involves wrists, ankles, and finally every joint. Some of studies have
      reported a reverse relationship between the level of vitamin D and RA severity.
      AIM: The present study was carried out in order to check the potential
      relationship between the level of vitamin D and RA severity. MATERIALS AND
      METHODS: Ninety-three patients with RA with onset in recent three months (new
      onset RA), and 31 patients without RA were chosen as the control group. The
      patients all aged under 75 years and were diagnosed by a rheumatologist. The
      serum level of vitamin D was measured through blood test by chemiluminescence
      method by taking a blood sample of 5 cc. The relationship between the average
      level of vitamin D and disease severity was analyzed based on scoring scale of
      DAS28 in different groups with RA. The significant level of the above mentioned
      tests was set at p<0.05. Data analysis was carried out using SPSS 20.0. RESULTS:
      The results of the present study indicated that there was no significant
      relationship between the two groups in terms of the serum level of vitamin D.
      Since the subgroups of the patients are not homogenous in terms of age and based
      on disease severity, ANOVA and chi-square were used to modify this heterogeneity
      and compare vitamin D levels in patients based on disease severity. The results
      indicated that there was a significant difference between the three groups of
      patients in terms of disease severity, such that disease severity rose with a
      decrease in the serum level of vitamin D, (p-value <0.001). CONCLUSION: There was
      a significant reverse relationship between the serum level of vitamin D and RA
      severity based on Das Score 28. Therefore, it is recommended that if there is a
      lack of or insufficient amounts of this vitamin in the body, vitamin D supply
      needs to be optimized along with other standard medications in order to reduce
      the RA severity.

PMID- 28511432
TI  - Mutations in Hepatitis-B X-Gene Region: Chronic Hepatitis-B versus Cirrhosis.
AB  - INTRODUCTION: Specific mutations in Hepatitis-B Virus (HBV) genome would proceed
      the development of chronic hepatitis B to more serious consequences like
      cirrhosis and end-stage liver disease. AIM: This study was designed to detect
      deletion and insertion mutational patterns in the X-gene region in a population
      of chronic HBV and related cirrhosis patients. MATERIALS AND METHODS: Sixty eight
      chronic HBV patients and 34 HBV-related cirrhotics were recruited from the
      eligible cases (N=50) referred to the academic hospitals of Gorgan city,
      Northeast of Iran, between Jan 2011 to Dec 2013. The HBx region was amplified by
      semi-nested PCR using serum samples and analyzed by sequencing. RESULTS: Our
      findings showed deletions and insertions in the C-terminal of HBx of the
      cirrhotic group and 8 bp found in two chronic HBV cases (2.9%). We detected 15
      types of deletions in cirrhotic cases such as 1762-1768, 1763-1770, 1769-1773 and
      T1771/A1775. CONCLUSION: We found that the frequencies of deletion and insertion
      mutations in C-terminal of X-gene were more seen in cirrhotic patients comparing
      to chronic HBV cases in our area of study.

PMID- 28511433
TI  - Clinico-Radiologic and Spirometric Profile of an Indian Population with Post
      Tuberculous Obstructive Airway Disease.
AB  - INTRODUCTION: Tuberculosis is a public health problem in developing countries and
      in spite of receiving adequate anti-tuberculous therapy, patients often continues
      to have several post-tuberculous sequelae, especially airflow limitation. AIM: To
      evaluate pulmonary function by spirometry among post-tuberculosis cases with
      airway obstruction and their relationship with smoking. MATERIALS AND METHODS:
      All patients who presented to the pulmonary medicine Outpatient Department (OPD)
      with symptoms of obstructive airway disease and had completed adequate anti
      tuberculous therapy for pulmonary tuberculosis were taken up for study. They were
      initially evaluated with sputum smear for Acid Fast Bacilli (AFB) and chest X
      ray. Patients without evidence of active tuberculosis underwent spirometry and
      those having post-bronchodilator Forced Expiratory Volume in first second (FEV1)/
      Forced Vital Capacity (FVC) FEV1/FVC<0.7 were taken up for final analysis.
      Spirometric parameters were compared between smokers and non-smokers. RESULTS:
      Out of 138 finally selected cases, 84.06% were male and 71.01% were within age
      range of 40-69 years. Significant positive association was found between extent
      of radiologic lesion and severity of airflow obstruction. Purely obstructive
      pattern was found in 27.54% cases and 72.46% showed mixed pattern. Patients with
      mixed ventilatory abnormality had worse pulmonary function and poorer
      bronchodilator reversibility than patients with pure obstruction. Comparison of
      post-bronchodilator FEV1, FVC, Peak Expiratory Flow (PEF) and Forced Expiratory
      Flow (FEF) 25-75 between smokers and non-smokers did not show statistically
      significant difference. CONCLUSION: Majority of patients with post-tuberculous
      obstructive airway disease have associated restrictive component. But smoking did
      not cause significant alteration in pulmonary function among such patients.

PMID- 28511434
TI  - Anti-C1q Antibody is Associated with Renal and Cutaneous Manifestations in Asian
      Indian Patients with Systemic Lupus Erythematosus.
AB  - INTRODUCTION: C1q play an important role in clearance of immune complexes and
      apoptotic cell debris. Impaired clearance leads to exposure of C1 native antigen
      and development of anti-C1q antibody formation. Anti-C1q antibody is well studied
      in Systemic Lupus Erythematosus (SLE). Significance of anti-C1q Ab in Indian SLE
      patients and their clinical manifestations is not clear. AIM: The aim of this
      study was to investigate associations between anti-C1q antibody and clinical as
      well as serological markers of SLE. MATERIALS AND METHODS: Retrospective study of
      SLE patients fulfilling either American College of Rheumatology (ACR) 1990 or
      Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification
      criteria were recruited from inpatients and outpatients services of the Clinical
      immunology and Rheumatology Department, Christian Medical College at Vellore,
      India between March 2013 and January 2015. Anti-C1q antibody was assayed by ELISA
      (Demeditec Diagnostics GmbH, Germany). Logistic regression analysis was performed
      to find the association of anti-C1q antibodies with serological and clinical
      parameters in SLE including Lupus Nephritis (LN). RESULTS: Sixty nine patients
      (54.76%) out of 126 SLE patients had LN. Anti-C1q levels were higher in patients
      with LN as compared to those without (p<0.05). Anti-C1q antibody was also
      significantly associated with positive C1q immunofluorescence staining in renal
      biopsy specimens (p<0.05). Overall, renal Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI) {OR 1.35 (1.08-1.69)}, low C4 {OR 3.11 (1.04-9.26)} and
      mucocutaneous manifestation {OR 4.72 (1.38-16.05)} were independently associated
      with anti-C1q levels in serum. CONCLUSION: Renal SLEDAI, low C4 and mucocutaneous
      manifestations were independently associated with raised anti C1q antibody in SLE
      patients.

PMID- 28511435
TI  - Agreement and Correlation between Arterial and Central Venous Blood Gas Following
      Coronary Artery Bypass Graft Surgery.
AB  - INTRODUCTION: Arterial blood sampling, used to assess patients in acute
      conditions, may result in complications such as thrombosis and embolism. However,
      it can be replaced by venous blood sampling, but there is a dearth of information
      on this. AIM: To assess the correlation and agreement between the arterial and
      central venous blood gases analyses in patients undergoing elective Coronary
      Artery Bypass Graft (CABG) surgery. MATERIALS AND METHODS: In this cross
      sectional study, 100 ICU patients undergoing elective CABG surgery were
      recruited. 2 mm arterial and a 2 mm venous blood samples were obtained from each
      patient's arterial and central venous lines, respectively. To predict Arterial
      Blood Gas (ABG) values based on central Venous Blood Gas (VBG) values, the linear
      regression analysis was used and for evaluating their agreement Bland-Altman
      method was used. RESULTS: In total of 200 samples were obtained. The mean and
      Standard Deviation (SD) of age was 58.9+/-9.1 years and 51% of the participants
      were female. There was a strong correlation between ABG and central VBG values
      regarding pH, partial Pressure of Carbon Dioxide (PCO2), Bicarbonate (HCO3) and
      Base Excess (BE) (r= 0.73, r=0.74, r=0.67 and r=0.71, respectively; p<0.001);
      however, the correlation between the arterial and venous Partial Pressure of
      Oxygen (PO2) and Oxygen Saturation (SO2) was moderate (r=0.29, p=0.005 and
      r=0.27, p=0.006, respectively). The Bland-Altman analysis showed an excellent
      agreement between all the variables (p<0.001). CONCLUSION: Central VBG analysis
      cannot replace ABG analysis in measuring exact PO2 status, necessitating arterial
      sampling in some matters, but with respect to the accuracy of pulse oximetry
      measurements in determining the exact PO2 status, for the rest of the indices a
      central VBG rather than an ABG can be utilised for determining patient's acid
      base status. Particularly in patients who are hospitalised for a long time and
      have a central venous catheter in place like patients who have undergone CABG,
      thus reducing the risk and need for invasive arterial sampling.

PMID- 28511436
TI  - Glycaemic and Insulin Response to Equi-Quantity of Selected Common Indian Staples
      in Individuals with Type 2 Diabetes Mellitus.
AB  - INTRODUCTION: Diet therapy is one of the corner stone's in the management of
      diabetes. Keeping the blood sugar level as close to normal is the main focus of
      dietary management of diabetes. A typical Indian meal is largely composed of
      Carbohydrates (CHO). Consumption of staple cereals, forms the major source of CHO
      in the Indian diet. However, CHO metabolism is seen to be completely deranged in
      a person with type 2 diabetes. It is necessary to select the cereal which has
      lower postprandial glycaemic impact for subjects with compromised metabolic
      status. Preference between two main staple cereals rice and wheat as staple food,
      especially for diabetic group, will depend on the equi-quantity based
      postprandial glycaemic impact of these cereals. AIM: To identify the cereals,
      better suited for individuals with diabetes (based on postprandial glycaemic and
      insulinemic impact of rice and whole wheat Indian flat bread i.e., chapatti).
      MATERIALS AND METHODS: After an overnight fast and upto 2 hours for every half an
      hour, finger tip blood samples for fasting and postprandial blood sugar was
      assessed. Venous blood for estimation of insulin levels were also collected from
      enrolled diabetic individuals and paired normal subjects. About 50 gm of test
      food like boiled rice, whole wheat chapatti and white bread as standard food were
      given on different occasions. Glucose and insulin levels were measured using
      glucometer and ECLIA method. RESULTS: Contrary to the popular belief, it was seen
      that rice exerted a lower peak and lower postprandial glycaemic and insulinemic
      response in both the study groups. Factors such as co-nutrient, moisture and
      fiber content all exert an impact on the postprandial glucose and insulin levels.
      With this the grain structure, particle size and amylose: amylopectin ratio are
      also important determinants. CONCLUSION: When foods are considered as a whole and
      not a single nutrient, rice proves to be a better product for effective
      management of blood sugars in individuals with type 2 diabetes mellitus.

PMID- 28511437
TI  - Children's Physical Activity Awareness among Mothers in a Saudi Arabian Health
      Center.
AB  - INTRODUCTION: Physical inactivity is a major contributor to the increasing levels
      of obesity and other serious medical conditions among children and adolescents
      worldwide. A major factor in this increase is lack of awareness of mothers'
      regarding the Physical Activity (PA) of their children. AIM: The current study
      aimed to identify the degree of knowledge and awareness of Saudi mothers'
      regarding their children's physical activities, which will be useful for
      improving physical education, health programs, and eventually children's health
      care. MATERIALS AND METHODS: A total of 342 mothers attending a vaccination
      clinic, well-baby, or women's health clinic participated in the study, in which
      questionnaire was used to assess the awareness regarding PA. RESULTS: The
      majority of mothers agreed that they have a crucial role in motivating their
      children to engage in PA, but was not aware of current recommendations.
      CONCLUSION: Awareness of Saudi mothers' regarding their children's PA was
      exceedingly low. Creating awareness of children's PA is essential.

PMID- 28511438
TI  - Assessing the Safety and Clinical Impact of Thoracoscopic Lung Biopsy in Patients
      with Interstitial Lung Disease.
AB  - INTRODUCTION: The clinical relevance of surgical lung biopsy in Interstitial Lung
      Disease (ILD) is supported in the literature. Yet most reports reflect
      institutional or personal bias. AIM: To evaluate the validity of radiologic
      diagnosis and clinical impact of lung biopsy to help clarify which patient
      benefit most from biopsy. MATERIALS AND METHODS: We performed a retrospective
      analysis of a prospectively managed database. All patients who had a surgical
      lung biopsy for ILD within a period of four year (2009 to 2013) were included.
      Data included patient demographics, peri-operative variables and outcomes.
      Preoperative Computed Tomography (CT) imaging was reviewed by a thoracic
      radiologist blinded to the original report and pathologic information. RESULTS: A
      total of 47 patients were included. Lung tissue was obtained via a thoracoscopic
      approach in all but two that had mini-thoracotomy. Mean operating time was 51.1
      minutes (18-123), median hospital stay was two days (1-18). Most (87.2%) of the
      patients were discharged within 72 hours. Thirty day mortality for elective
      surgery was 4.5% (2/44). Post-operative complications occurred in about one third
      of the patients. Complications in elective procedures included pneumothorax
      (10.4%), re-intubation (5.4%) and prolonged intubation (2.7%). Full concordance
      of radiographic diagnosis with the final diagnosis was significantly higher when
      reviewed by a cardiothoracic radiologist (60.5% vs. 21.3%). The preoperative
      clinical diagnosis was fully concordant with the final diagnosis in only 28.2% of
      cases. In 13.0% of patients the preoperative diagnosis was incorrect. Malignancy
      was the final diagnosis in two (4.3%) patients. In 51.1% of the patients, results
      of the biopsy did alter therapy. CONCLUSION: Diagnosis of specific ILD by a
      cardiothoracic radiologist is more specific and accurate and will probably lead
      to more appropriate therapy. Elective thoracoscopic surgical lung biopsy is a
      safe procedure, leads to a more accurate diagnosis of ILD and impacts therapy.

PMID- 28511440
TI  - Portal Venous Thrombosis: Eosinophilic Vasculitis.
AB  - Portal Vein Thrombosis (PVT) is caused by various thrombophilic states. PVT
      secondary to underlying vasculitis especially Churg-Strauss disease is among the
      rarest presentation. Here, we report a case of peripheral eosinophilia,
      eosinophilic ascitis and venous thrombosis involving portal vein and superior
      mesenteric vein diagnosed as Churg-Strauss Syndrome (CSS). He was managed with
      steroids and anticoagulants. Following initiation of steroids, eosinophilia and
      eosinophilic ascitis improved.

PMID- 28511439
TI  - Light Chain Myeloma induced Severe Hypertriglyceridemia.
AB  - Hyperlipidemia is very common in general population and incidence has further
      increased in recent years. Evaluation of patient presenting with lipid disorders
      is essential to obtain a definite diagnosis to prevent complications, and apply
      the most appropriate treatment. An isolated elevation in triglyceride levels may
      be caused by a primary disorder of lipid metabolism like familial
      hypertriglyceridemia. It may also arise secondary to a number of conditions like
      diabetes mellitus, alcohol intake, hypothyroidism, drugs, infections and
      nephrotic syndrome. Herein, we describe a case of secondary hypertriglyceridemia
      leading to Nonalcoholic Steatohepatitis (NASH) in a young female which was
      attributed to Multiple Myeloma (MM). Significant reduction in triglyceride levels
      after starting anti-myeloma therapy established their relation. This is the first
      case of light chain myeloma causing severe secondary hypertriglyceridemia.

PMID- 28511441
TI  - Catheter-Assisted Balloon-Supported Retrieval of a Broken Semi-Compliant Balloon
      from a Coronary Artery.
AB  - Incidents of broken balloon in a coronary vasculature during percutaneous
      coronary angioplasty are very rare. Such events in cath-lab may create panic and
      can be life threatening for patients. Hence, immediate retrieval of broken
      balloon becomes vital. Here, we report an unusual complication of broken balloon
      in the mid portion of the left anterior descending coronary artery, which had a
      calcified and totally occluded in-stent restenotic lesion. The broken balloon was
      retrieved successfully with no eventual complication using a simple catheter
      assisted balloon-supported retrieval technique. The present case highlights the
      need for interventional cardiologist to be acquainted with different retrieval
      techniques.

PMID- 28511442
TI  - Cannon Ball Lung Metastases from a Previously Unreported Primary.

PMID- 28511443
TI  - Patent Vitellointestinal Duct with Patent Urachus Presenting as Umbilical
      Discharge.
AB  - Patent urachus with patent vitellointestinal duct is a rare combination to
      present in the same patient. We present a rare case of one year old male child
      with such a condition presenting with complaint of discharge from umblicus along
      with severe anaemia and an umblical granuloma. On exploratory laparotomy, patent
      tracts joining umblicus to ileum and umblicus to apex of urinary bladder were
      found. Both the tracts were excised and appropriate closure was done. Patient had
      been under follow up and is doing well.

PMID- 28511444
TI  - Pseudoangiomatous Stromal Hyperplasia: A Rare Cause of Breast Lump in a
      Premenopausal Female.
AB  - Pseudoangiomatous Stromal Hyperplasia (PASH) of the breast is a rare benign
      proliferating breast condition. We report a case of a 26-year-old female who was
      being worked up for infertility and was incidentally noted to have a well defined
      lump in the left breast. Fine Needle Aspiration Cytology (FNAC) and core needle
      biopsy of the lump were suggestive of benign breast disease. Patient underwent
      excision of the lump. Histopathology report of which was suggestive of PASH of
      the breast.

PMID- 28511445
TI  - Neoumbilicoplasty in a Laparoscopic Port Site: Description of a New Technique and
      Review of Literature.
AB  - The umbilicus contributes significantly to the cosmetic appearance of the abdomen
      especially in women. Loss of umbilicus may result not only in cosmetic
      disfigurement but also in significant psychological effects. Omphalectomy may
      accompany certain surgical procedures like ventral hernia repairs and
      abdominoplasty. For such patients, many techniques have been described by various
      authors in literature for creation of a neoumbilicus for good cosmetic
      appearance. In this report, we describe how a laparoscopic port site was utilized
      to create a neoumbilicus in a patient who required omphalectomy as a part of
      large umbilical hernia repair. Satisfactory postoperative result promted us to
      report this novel technique of neoumbilicus creation. This can be utilized in
      patients who have been previously subjected to laparoscopic procedures. This is
      the first case description in literature where a laparoscopic port scar was
      utilized for neoumbilicoplasty.

PMID- 28511446
TI  - Thromboangitis Obliterans involving Bilateral Upper limb Extremities - A Rare
      Case Report from Malaysia.
AB  - Thromboangitis Obliterans (TAO) or Buerger's disease is a non-atherosclerotic,
      occlusive, progressive and highly inflammatory disorder of distal arteries seen
      predominantly affecting the lower limb in smokers. TAO presenting itself in upper
      limb or bilaterally involving the upper limb is a very rare entity. We report on
      a rare case of TAO in a 46-year-old gentleman who presented with bilateral upper
      extremity digital gangrene with 18 pack-years of smoking. Brachial and radial
      pulses were palpable bilaterally and were of good volume but right ulnar pulse
      was faintly felt, while on the left side it was not appreciated due to malunion.
      Further Computed Tomography (CT)- angiography showed occlusion of distal right
      ulnar artery, stenosis of distal left ulnar artery with bilateral poor
      opacification of palmar and digital arteries. This case reports on the unusual
      and rare presentation of TAO in upper extremity involving both limbs. The case is
      reported for the first time from Malaysia.

PMID- 28511448
TI  - Rectus Sheath Haematoma Secondary to Enoxaparin Injection- A Rare Case Report.
AB  - Rectus sheath haematoma is a well-documented condition with an elusive diagnosis.
      It is an uncommon complication of anti-coagulation therapy, which can have a
      mortality of upto 25%. The patient discussed here is a 40-year-old female who was
      on Inj. Enoxaparin, who developed severe abdominal pain and hypovolemia after
      three days of treatment. Ultrasonography and CT scan showed a large rectus sheath
      haematoma on the right side, which was crossing the midline towards the left
      side. Inj. Enoxaparin was stopped and the patient was posted for surgery. In
      surgery, all clots were evacuated and inferior epigastric vessels were ligated.
      Patient recovered well following surgery. Here, this report presents forward a
      case of rectus sheath haematoma secondary to enoxaparin injection, its
      presentation and its surgical management.

PMID- 28511447
TI  - Delayed Presentation of Isolated Jejunal Perforation Following Accidental Trauma.
AB  - Blunt abdominal trauma can injure any abdominal organs which had significant
      morbidity and mortality in paediatric age group. It can lead to duodenal, jejunal
      or rather any bowel perforation. Isolated jejunal perforation still remains rare
      entity with less documented reports in specifically paediatric age group. We
      hereby present a case of three-year-old female child with isolated jejunal
      perforation, post history of fall from height. Early exploration and prompt
      surgical intervention led to successful outcome in this patient.

PMID- 28511449
TI  - Management of Accidental and Iatrogenic Foreign Body Injuries to Heart- Case
      Series.
AB  - Accidental and iatrogenic foreign body injuries to heart require immediate
      attention and its timely management is cornerstone to the life of an individual.
      We describe in detail five cases of Accidental and iatrogenic foreign body
      injuries to heart encountered between January 2013 and July 2016. Our series
      included the following: needle stick injury to the right atrium (1 case) retained
      catheter fragments in the distal main pulmonary artery (1 case), right ventricle
      injury during catheterisation study (1 case), right ventricle injury during
      permanent pacemaker lead placement (1 case), device migration in atrial septal
      defect closure (1 case). Foreign bodies were removed from the cardiac cavities
      when the patient presented with features of infection (1 case), cardiac tamponade
      (2 case), anxiety (1 case), and haemodynamic instability (1 case). The management
      of accidental and iatrogenic foreign body injuries to heart requires immediate
      attention. Foreign bodies in the heart should be removed irrespective of their
      location and symptomatology. Asymptomatic foreign bodies diagnosed immediately
      after the injury with associated risk factors should be removed; asymptomatic
      foreign bodies without associated risks factors or diagnosed accidentally after
      the injury also need surgical intervention to allay fears of anxiety in patient
      and their relatives, to prevent any late complications and also for medico-legal
      purpose.

PMID- 28511450
TI  - Emergency Peripartum Hysterectomy: Indications and Outcome in a Tertiary Care
      Setting.
AB  - INTRODUCTION: Emergency Peripartum Hysterectomy (EPH) is an important lifesaving
      procedure, mostly reserved for conditions deemed to be serious and life
      threatening, and not amenable to conservative methods. In the present scenario,
      the advent of newer medical and conservative surgical methods for controlling
      obstetric haemorrhage has influenced the incidence, trend and the outcomes of the
      procedure. AIM: To evaluate the demographic profile, indications, operative
      details, maternal morbidity and mortality and neonatal outcomes of women
      undergoing EPH. MATERIALS AND METHODS: A descriptive analysis of case records of
      women who underwent EPH between September 2006 to July 2014, at Guru Teg Bahadur
      Hospital Delhi, India was done. Data were collected from the medical records
      department. RESULTS: A total of 194 cases (n) were identified among 1,00712
      deliveries, an incidence of 1.92 per 1000 deliveries. Majority of the women were
      unbooked i.e., they did not receive any form of antenatal care and were gravida 3
      and above. The indications were atonic PPH in 89 (45.87%), rupture of unscarred
      uterus in 36 (18.56%), morbidly adhered placenta in 30 (15.46%), scar rupture in
      20 (10.31%) and gangrenous uterus 19 (9.79%). The mean blood loss was around
      1.6+/-0.45 litres. Approximately 14% cases underwent stepwise devascularisation
      prior to hysterectomy and in only 2% women, B-Lynch suture was applied. Thirteen
      (6.7%) cases had bladder injury and 22 (11.34%) needed re-laparotomy for
      hysterectomy. Around 76 (39%) women were shifted for ICU care. Nineteen (9.79%)
      women developed Disseminated Intravascular Coagulation (DIC). The case fatality
      rate was 7.2% and perinatal mortality was 30%. CONCLUSION: Atonic PPH remains the
      leading cause of EPH in our analysis. Surprisingly rupture of unscarred uterus
      was more common compared to scar rupture. Creating awareness among women to seek
      health services in time with facilities for early referral, teaching younger
      obstetricians with conservative surgical procedures like stepwise
      devascularisation steps and compressive sutures should be of utmost priority.

PMID- 28511451
TI  - Attitudes of Mashhad Public Hospital's Nurses and Midwives toward the Causes and
      Rates of Medical Errors Reporting.
AB  - INTRODUCTION: Patient's safety is one of the main objective in healthcare
      services; however medical errors are a prevalent potential occurrence for the
      patients in treatment systems. Medical errors lead to an increase in mortality
      rate of the patients and challenges such as prolonging of the inpatient period in
      the hospitals and increased cost. Controlling the medical errors is very
      important, because these errors besides being costly, threaten the patient's
      safety. AIM: To evaluate the attitudes of nurses and midwives toward the causes
      and rates of medical errors reporting. MATERIALS AND METHODS: It was a cross
      sectional observational study. The study population was 140 midwives and nurses
      employed in Mashhad Public Hospitals. The data collection was done through
      Goldstone 2001 revised questionnaire. SPSS 11.5 software was used for data
      analysis. To analyze data, descriptive and inferential analytic statistics were
      used. Standard deviation and relative frequency distribution, descriptive
      statistics were used for calculation of the mean and the results were adjusted as
      tables and charts. Chi-square test was used for the inferential analysis of the
      data. RESULTS: Most of midwives and nurses (39.4%) were in age range of 25 to 34
      years and the lowest percentage (2.2%) were in age range of 55-59 years. The
      highest average of medical errors was related to employees with three-four years
      of work experience, while the lowest average was related to those with one-two
      years of work experience. The highest average of medical errors was during the
      evening shift, while the lowest were during the night shift. Three main causes of
      medical errors were considered: illegibile physician prescription orders,
      similarity of names in different drugs and nurse fatigueness. CONCLUSION: The
      most important causes for medical errors from the viewpoints of nurses and
      midwives are illegible physician's order, drug name similarity with other drugs,
      nurse's fatigueness and damaged label or packaging of the drug, respectively.
      Head nurse feedback, peer feedback, fear of punishment or job loss were
      considered as reasons for under reporting of medical errors. This research
      demonstrates the need for greater attention to be paid to the causes of medical
      errors.

PMID- 28511452
TI  - The Effect of Entonox on Labour Pain Relief among Nulliparous Women: A Randomized
      Controlled Trial.
AB  - INTRODUCTION: Labour pain is one of the most severe pain in humans. Fear of
      labour pain is the most dreadful reason for Caesarean Section (CS). Entonox (a
      mixture of nitrous oxide+oxygen) is a safe inhalational analgesia during labour
      pain. AIM: This study investigated the effect of entonox on pain relief and
      length of labour in nulliparous women. MATERIALS AND METHODS: A clinical trial
      study was conducted among 120 nulliparous women (60 in intervention and 60 in
      control group) in 2015 in Atieh Hospital, Hamadan city, Iran. The women were
      chosen randomly to receive either entonox in the intervention group or oxygen in
      the control group. For the intervention group, entonox inhalation was introduced
      at the initiation of pain at each contraction. entonox gas was administrated via
      a face-mask. This enabled the women to breathe fresh gas in each inspiration. In
      the control group the oxygen inhalation was given with occurrence of pain at each
      contraction too. In both groups, the gas administration continued until the end
      of contraction pain with the patient finally breathing room air. Pain using
      Visual Analogue Scale (VAS), duration of labour and side effects were compared in
      two groups. RESULTS: The mean age of women was 25.69 (SD=4.83). There were
      significant differences between two groups on labour pain at the first, second,
      third and fourth hours after intervention (p<0.05). Duration of labour in the
      intervention group (64.80 minutes) was significantly shorter than the control
      group (98.33 minutes) (p<0.05). There were no significant differences between the
      two groups on women's blood pressure and neonatal Apgar score. Only dizziness was
      slightly higher in the intervention group compared to the control group (p<0.05).
      CONCLUSION: Entonox provides significant pain relief and it can quickly be
      implemented during painful labour.

PMID- 28511453
TI  - Pregnancy Outcome of Abnormal Nuchal Translucency: A Systematic Review.
AB  - INTRODUCTION: Nuchal Translucency (NT) is the sonographic form of subcutaneous
      gathering of liquid behind the foetal neck in the first trimester of pregnancy.
      There is association of increased NT with chromosomal and non-chromosomal
      abnormalities. AIM: The purpose of this systemic review was to review the
      pregnancy outcome of abnormal nuchal translucency. MATERIALS AND METHODS: The
      present systematic review was conducted by searching English language articles
      from sources such as International Medical Sciences, Medline, Web of science,
      Scopus, Google Scholar, PubMed, Index Copernicus, DOAJ, EBSCO-CINAHL. Persian
      articles were searched from Iranmedex and SID sources. Related key words were
      "outcome", "pregnancy", "abnormal", and "Nuchal Translucency" (NT). All,
      randomized, descriptive, analytic-descriptive, case control study conducted
      during 1997-2015 were included. RESULTS: Including duplicate articles, 95 related
      articles were found. After reviewing article titles, 30 unrelated article and
      abstracts were removed, and 65 articles were evaluated of which 30 articles were
      duplicate. Finally 22 articles were selected for final analysis. Exclusion
      criteria were, case studies and reports and quasi experimental designs. This
      evaluation has optioned negative relationship between nuchal translucency and
      pregnancy result. Rate of cardiac, chromosomal and other defects are correlated
      with increased NT>=2.5mm. Cardiac disease which were associated to the increased
      NT are heart murmur, systolic organic murmur, Atrial Septal Defect (ASD),
      Ventricular Septal Defect (VSD), tricuspid valve insufficiency and pulmonary
      valve insufficiency, Inferior Vena Cava (IVC) and Patent Ductus Arteriosus (PDA).
      The most common problems that related with increased NT were allergic symptoms.
      CONCLUSION: According to this systematic review, increased NT is associated with
      various foetal defects. To verify the presence of malformations, birth defect
      consultations with a perinatologist and additional tests are required.

PMID- 28511454
TI  - The Factor Structure and Psychometric Properties of the Persian Version of the
      Revised Prenatal Coping Inventory (Nu-PCI).
AB  - INTRODUCTION: Familiarity with coping strategies is essential for stress
      management during pregnancy. The Revised Prenatal Coping Inventory (Nu-PCI) was
      developed to assess coping strategies during pregnancy. AIM: This study aimed to
      assess the factor structure and psychometric properties of the Persian version of
      the Nu-PCI. MATERIALS AND METHODS: After forward-backward translation, the Nu-PCI
      was administered to 210 pregnant women who were enrolled in two teaching referral
      clinics in the North of the Islamic Republic of Iran (Babol). The participants
      completed the Persian Nu-PCI and Ways of Coping Questionnaire (WCQ), which was
      used to determine the validity of the Persian Nu-PCI. To test construct validity
      of the Persian Nu-PCI, a principal components factor analysis was performed.
      RESULTS: Principal components analysis with varimax rotation showed a best
      fitting 3-factor structure similar to the original with three coping subscales:
      planning-preparation, avoidance, and spiritual-positive coping. The Persian Nu
      PCI was internally consistent and within the acceptable range (alpha=0.89-0.97).
      The alpha coefficients for the Nu-PCI and the subscales of planning-preparation,
      avoidance, and spiritual-positive coping were high. Test-retest coefficients for
      the Nu-PCI and subscales were 0.98-0.99. The Nu-PCI and its subscales correlated
      with the WCQ in the entire sample and within each trimester. CONCLUSION: The
      Persian version of the Nu-PCI and the subscales of planning-preparation,
      avoidance, and spiritual-positive coping represent the first reliable
      standardized tool for measuring coping strategies during pregnancy in the Islamic
      Republic of Iran. Therefore, it can be applied as a quick and accurate
      preliminary screening tool for evaluating coping strategies throughout pregnancy
      in clinics and other medical and research settings.

PMID- 28511455
TI  - Cervical Conization and the Risk of Preterm Birth: A Population-Based
      Multicentric Trial of Turkish Cohort.
AB  - INTRODUCTION: Cold Knife Conization (CKC) is one of the most effective methods
      for the treatment of Cervical Intraepithelial Neoplasia (CIN). Some studies
      showed a relation between preterm birth and the treatment of CIN; on the other
      hand, other studies do not show such a relationship. AIM: The present study was
      conducted with the aim to investigate the pregnancy outcomes of Turkish women
      regarding demographic characteristics, obstetric history, removed tissue, and
      residual cervical length after CKC and to determine the effect of removed
      cervical tissue volume and height on preterm birth. MATERIALS AND METHODS: This
      study was a population-based, multicenter trial that was conducted on singleton
      pregnancies between January 2007 and December 2013. The control group comprised
      of 38,892 patients who gave birth during this period. On the other hand, patients
      who conceived after CKC during this period were invited to the hospital and
      included in the case group (n=20). The course of pregnancy following CKC was
      studied. Preterm birth rates, risk factors for preterm birth, conisation age,
      cervical smear and colposcopic biopsy results and the volume and height of the
      removed cervical tissue of those patients were evaluated. RESULTS: There was no
      statistically significant difference in preterm birth rates between the case and
      the control groups. None of our cases had any identified preterm birth risk
      factor except for one case. The average height of removed cervical tissue was
      12.6+/-5.4 mm and the average length of the residual cervix after birth was
      28.7+/-4.3 mm. CONCLUSION: Removal of cervical tissue of 12.6+/-5.4 mm in height
      and 2.35+/-2.27 cm3 in volume will not increase the risk of preterm birth of
      women who do not have any other preterm birth risk factors. If there is no other
      preterm birth risk factors, term birth is most probably possible after
      conisation.

PMID- 28511456
TI  - Acute Rubella Virus Infection among Women with Spontaneous Abortion in Mwanza
      City, Tanzania.
AB  - INTRODUCTION: Acute rubella virus infection in early pregnancy has been
      associated with poor pregnancy outcome ranging from spontaneous abortion,
      stillbirth and multiple birth defects known as Congenital Rubella Syndrome (CRS).
      Despite its importance the prevalence of acute rubella virus infections is not
      known among women with spontaneous abortion in most centres in developing
      countries. AIM: The present study was aimed to determine the seroprevalence of
      acute rubella infection among women with spontaneous abortion in Mwanza city.
      MATERIALS AND METHODS: A total of 268 women with spontaneous abortion were
      enrolled from four different hospitals in Mwanza city between November 2015 and
      April 2016. Blood samples were collected; sera were extracted and stored at -80
      degrees C until processing. Acute rubella virus infection was diagnosed by the
      detection of rubella specific IgM antibodies using indirect Enzyme Linked
      Immunosorbent Assay (ELISA) as per manufacturer's instructions. Data were
      analysed by using STATA version 11. RESULTS: The mean age of enrolled women was
      26.3+/-5.6 years. The prevalence of acute rubella virus infection was found to be
      9/268 (3.7%, 95% CI: 1-5). Only women residing in urban areas (AOR: 5.65, 95% CI:
      1.15-27.77, p=0.035) were found to predict acute rubella virus infection among
      cases with spontaneous abortion in Mwanza city. CONCLUSION: About four out of
      hundred women residing in urban areas with spontaneous abortion in Mwanza are
      acutely infected with rubella virus highlighting the potential of this virus in
      contributing to poor pregnancy outcome in this setting.

PMID- 28511457
TI  - Leptin as a Predictive Marker in Unexplained Infertility in North Indian
      Population.
AB  - INTRODUCTION: According to WHO, the primary infertility in India is about 3.9%
      (age-standardized to 25-49 year) and 16.8% (age-standardized to 15-49 year),
      using the "age but no birth" definition. Several factors which affect fertility
      include low sperm production in men, poor egg quality and blocked fallopian tubes
      in women and also hormonal imbalances. Leptin plays a critical role in women's
      reproduction and neuroendocrine health. It is used for treating exercise-induced
      bone loss, eating disorders and infertility. AIM: To evaluate the serum leptin
      levels in Indians and to ascertain the relationship between serum leptin levels,
      Unexplained Infertility (UI) and related variables [height, weight, Waist Hip
      Ratio (WHR), Body Mass Index (BMI)] between obese infertile, non-obese infertile
      and healthy subjects. MATERIALS AND METHODS: The present case-control study was
      conducted at the Department of Obstetrics and Gynaecology, King George's Medical
      University (KGMU), Lucknow, India and funded by Department of Science and
      Technology, New Delhi, India. The study included 229 female participants in the
      age group of 18-40 years (120 cases and 109 controls) who were randomly selected.
      The blood samples were collected from the Infertility Clinic, Queen Mary's
      Hospital, KGMU, Lucknow, India. All the participants underwent complete physical
      examination. Initially, the participants were categorized into fertile and
      infertile groups, they were further divided on the basis of BMI, normal (BMI-
      18.5-24.5) and overweight or obese (BMI>=25). Leptin level was measured by Active
      Human Leptin ELISA kit and BMI of all subjects was calculated in kg/m2 (weight in
      kg and height in m). RESULTS: A highly positive linear correlation (R=0.754,
      p<0.001) was found between BMI and serum leptin in unexplained infertile women,
      which indicates a strong relationship between BMI and serum leptin. The variation
      in serum leptin is explained by the independent variable, BMI. There was a
      partial positive linear correlation between BMI and serum leptin in the control
      group. Statistically there was no significant correlation (R=0.109, p=0.258)
      between BMI and serum leptin in the control group. CONCLUSION: The present study
      clearly demonstrates that level of leptin is higher in unexplained infertile than
      in the fertile group, and also shows that a strong relationship exists between
      BMI and serum leptin in the obese group. Serum leptin level was significantly
      higher in obese than non-obese subjects. Thus, leptin is an important factor for
      normal reproductive function. Obesity, the main cause of infertility may be
      controlled by regulating the leptin concentration.

PMID- 28511458
TI  - Maternal and Cord Blood Plasma sEng and TGF-beta1 in Patients with Hypertensive
      Disorders of Pregnancy: A Pilot Study in a South Indian Population.
AB  - INTRODUCTION: Hypertensive Disorders of Pregnancy (HDP) are one of the most
      widespread complications of pregnancy that affects both mother and foetus. It has
      been observed that in Preeclampsia, the release of soluble angiogenic factors
      from the ischemic placenta into maternal plasma plays a crucial role in the
      pathogenesis. AIM: To assess the plasma Soluble Endoglin (sEng) and Transforming
      Growth Factor (TGF-beta1) levels in various types of HDP and to correlate the
      levels of these markers with the pregnancy outcome. MATERIALS AND METHODS: A
      total of 128 pregnant women were recruited and the study was carried out for a
      period of three years. Cord blood and maternal blood plasma levels of sEng and
      TGF-beta1 were analysed by ELISA kits in Control Pregnant Women (CPW),
      Gestational Hypertension (GH), Early Onset Preeclampsia (EOPE), Late Onset
      Preeclampsia (LOPE), and Eclampsia (E) during third trimester. The Gestational
      Age (GA) at the time of delivery and Birth Weight (BW) of the baby also were also
      evaluated. RESULTS: The circulating levels of maternal and cord blood sEng were
      significantly higher in EOPE and E compared to CPW and GH. However, the maternal
      and cord blood levels of TGF-beta1 were significantly lower in LOPE and E when
      compared to CPW and GH. The GA and BW of the baby were found to be significantly
      lower in EOPE and E compared to CPW, GH and LOPE. Also, a negative correlation
      was observed between sEng levels with pregnancy outcome; GA and BW. And also, a
      positive correlation was found between TGF-beta1 and pregnancy outcome.
      CONCLUSION: A generalised angiogenic imbalance and poor birth outcomes were
      observed in HDP. There is a spectrum of biochemical derangements related to
      angiogenesis in GH, EOPE, LOPE and E.

PMID- 28511459
TI  - A Comparison of 2-Methoxyestradiol Value in Women with Severe Preeclampsia Versus
      Normotensive Pregnancy.
AB  - INTRODUCTION: Preeclampsia is a pregnancy complication characterized by high
      blood pressure and proteinuria. Endothelial dysfunction is a major theory
      suggested as its aetiology. It is caused by anti-angiogenic condition
      characterized by low Vascular Endothelial Growth Factor (VEGF). An estradiol
      metabolite, called 2-Methoxy Estradiol (2-ME), is produced with the help of
      Catechol-O-Methyltransferase (COMT). This substance has an important role in VEGF
      expression. A 2-ME is suppressed in women with preeclampsia. AIM: To compare 2-ME
      in women with severe preeclampsia and normotensive pregnancy. MATERIALS AND
      METHODS: A total of 80 subjects qualified the inclusion and exclusion criteria,
      were divided into two groups (40 each): the severe preeclampsia and the
      normotensive pregnancy. Blood sample was collected and examined with the ELISA 2
      ME kit (Cayman). The data were compared and calculated using Fisher-Exact test to
      examine 2-ME differences between the two groups. RESULTS: Women age, parity, and
      gestational age showed a non significant difference between both groups.
      Nonetheless, the BMI before pregnancy and the history of preeclampsia in the past
      pregnancy showed significant differences. In this study, the 2-ME value was lower
      in the severe preeclampsia group compared to the normotensive. CONCLUSION: This
      study concludes that 2-ME value in severe preeclampsia is lower than normotensive
      pregnancy. A lower 2-ME value may indicate COMT not producing enough 2-ME which
      in turn may cause the pre-eclampsia.

PMID- 28511460
TI  - Cuff Closure by Vaginal Route in TLH: Case Series and Review of Literature.
AB  - Total Laparoscopic Hysterectomy (TLH) represents one of the most performed
      gynaecological procedures nowadays. The closure of the vaginal cuff is the most
      diffucult part of TLH because of the difficulty of laparoscopic suturing
      techniques. Our aim was to evaluate the efficacy and safety of vaginal cuff
      closure by vaginal route on patients submitted to TLH. During the period between
      January 2013 to December 2015 total number of 64 laparoscopic hysterectomy were
      performed in our clinic. TLH and vaginal vault closure was performed as described
      by Ghezzi for all patients. The length of cuff closure time and the frequency of
      vaginal cuff-related complications were measured. Mean age was 48.1 (38-71)
      years, mean parity was 2.6 (1-9). Most ranked indications for hysterectomy were
      abnormal uterine bleeding and symptomatic leiomyoma. Average cuff closure time
      was 6 (2-17) minute. In average 24 (2-36) month follow-up there were no vaginal
      vault dehiscence. Transvaginal vaginal cuff closure seems to be safe, easy and
      effective for total vaginal hysterectomy. Using vaginal route can significantly
      reduce the length of closure time. This technique has comparable complication
      rates with endoscopic suturing techniques.

PMID- 28511461
TI  - Cervical Pregnancy Masquerading as an Incomplete Abortion- A Learning Lesson.
AB  - Cervical pregnancy is a rare site of ectopic pregnancy compared to tubal. The
      trophoblast implant into the cervical tissue and become a potentially dangerous
      site of torrential haemorrhage. The widespread use of Ultrasonography (USG) has
      led to a dramatic increase in the detection rates of extra uterine pregnancy. We
      hereby report an interesting case of extra uterine pregnancy with a unique
      situation where only a high index of suspicion prevented an iatrogenic mishap.
      The patient was referred as a case of incomplete abortion with a documented
      report of minimal retained products. Because of a high index of suspicion a serum
      beta Human chorionic gonadotropin (hCG) was sent prior to deciding for discharge.
      This indeed turned as a major change in the diagnosis of the case as the serum
      beta hCG was elevated. On re-evaluation, we diagnosed it as a case of cervical
      pregnancy which was successfully managed medically.

PMID- 28511462
TI  - Story of a Giant Endometrial Polyp in Asymptomatic Postmenopausal Female.
AB  - Endometrial polyps are localized overgrowth of endometrial glands and stoma
      through the uterine cavity. They are associated with postmenopausal bleeding,
      infertility and menorrhagia and are affected by unbalanced oestrogen therapy or
      increased frequency of tamoxifen exposure. We report a case of giant endometrial
      polyp in postmenopausal female without vaginal bleeding and hormone or drug use.
      A 65-year-old, postmenopausal female P3L2 with hypertension and Diabetes Mellitus
      (DM) came for routine health check-up. Her physical examination was normal.
      Pelvic examination uterus was multiparous sized, mid positioned and bilateral
      fornices were free. Patient was planned for hysteroscopic guided biopsy as her
      Ultrasonography (USG) showed endometrial thickness to be 12.3 mm. On
      hysteroscopy, there was hyperplastic endometrium with large endometrial polyp of
      size 8.5 cm. Polypectomy was done and the same was sent for histopathological
      evaluation. Report showed cystic hyperplasia without atypia. To summarize,
      postmenopausal female will not always present with symptoms and USG can also
      quite frequently miss the diagnosis, so proper evaluation is needed using
      hysteroscopy which is gold standard for diagnosis and treatment of endometrial
      polyp.

PMID- 28511463
TI  - Unusually High Serum Levels of CA 19-9 in an Ovarian Tumour: Malignant or Benign?
AB  - Carbohydrate antigen 19-9 (CA 19-9) is a tumour marker found to be elevated in
      some ovarian tumours. We share our experience with a 55-year-old postmenopausal
      lady with unusually high CA19-9 levels arising from a benign mucinous cystadenoma
      of the ovary. The levels returned to normal eight weeks following staging
      laparotomy and a total abdominal hysterectomy with bilateral salpingo
      oopherectomy. This report shows rare and significant elevation of CA 19-9 levels
      with benign mucinous cystadenomas of the ovary thus showing that women with
      unusually elevated tumour markers may actually harbour benign disease. The tumour
      markers should not be used to predict the malignant status of a tumour.

PMID- 28511464
TI  - A Study to Assess the Functional Outcome of Decompression and Posterior Lumbar
      Interbody Fusion of Low Grade Spondylolisthesis of Lumbar Vertebra.
AB  - INTRODUCTION: Spondylolisthesis is defined as the forward displacement of one
      vertebra over the vertebra below. It is often accompanied by spinal canal
      stenosis and compression, which is the cause of all the symptoms. AIM: To assess
      and study the functional outcome after decompression and Posterior Lumbar
      Interbody Fusion (PLIF) of isthmic spondylolisthesis of lower lumbar vertebra and
      to study the complications occurring with this technique. MATERIALS AND METHODS:
      A prospective study was conducted in the Department of Orthopaedics in Justice KS
      Hegde Charitable Hospital, Mangalore, Karnataka, India from March 2015 to August
      2016. A total of 15 diagnosed patients with Grade I and II spondylolisthesis of
      L4-L5 and L5-S1 vertebrae with no neurological deficits, between the age group of
      25-50 were included in the study. An initial two months of conservative treatment
      of back physiotherapy and flexion exercises was tried. Patients who did not
      improve with the conservative therapy were taken up for surgery with consent.
      Decompression and PLIF with bone grafting with interbody cage placement and
      pedicle screw instrumentation was performed. The patients were discharged on
      postoperative day 10 after suture removal. They were reviewed at postoperative
      day 10, week six and week 24. The scoring of the functional outcome of the back
      was done as per the Modified Oswestry low back pain Disability Questionnaire. The
      statistical analyses were done using the repeated measures ANOVA, SPSS version
      20. RESULTS: The mean Modified Oswestry low back pain Disability score
      preoperatively was noted to be 42.87+/- 3.46 points. The mean Modified Oswestry
      low back pain Disability score at postoperative day 10 was noted to be 36.93+/
      3.75 points. The mean Modified Oswestry low back pain Disability score at
      postoperative week six was noted to be 28.47+/-3.70 points. The mean Modified
      Oswestry low back pain Disability score at postoperative week 24 was noted to be
      24.27+/-3.01 points. Improvement in the Modified Oswestry low back pain
      Disability scores was noted during the follow ups. Foot drop was noted in two
      cases postoperatively which improved during the final follow up with
      physiotherapy. CONCLUSION: Decompression and PLIF is noted to produce good to
      satisfactory functional results in cases of isthmic spondylolisthesis of lower
      lumbar vertebra.

PMID- 28511465
TI  - Digging Deeper into the Patello - Femoral Joint: Patello - Femoral Composite - A
      New Dimension for Overstuffing of Patello - Femoral Joint.
AB  - INTRODUCTION: Patello-femoral complications are the most common complications in
      postoperative Total Knee Arthroplasty (TKA) patients especially overstuffing of
      Patello - Femoral Joint (PFJ). So, to study the effects of overstuffing of PFJ in
      postoperative TKA patients we put forth a new dimension - "PATELLO - FEMORAL
      COMPOSITE (PFC)". This is the maximum distance between anterior cortical line of
      femur shaft and the anterior cortex of patella with knee in full extension. AIM:
      To calculate chances of overstuffing of PFJ in postoperative TKA patients and
      document the effect of overstuffing of PFJ on the passive knee Range of Motion
      (ROM) in post- op TKA patients. MATERIALS AND METHODS: This was a prospective
      observational study which included 51 consecutive primary TKAs. Preoperative and
      postoperative (24 weeks) passive knee ROM was measured. Preoperative and
      postoperative radiological parameters {PFC, Anterior Femur Offset (AFO), Patellar
      thickness (PT)} was recorded using Computed Tomography (CT) Scanogram image of
      patient in lateral view with knee in full extension and perfect overlap of both
      femur condyles, using DICOM format of the CT Scanogram image on the DICOM viewer.
      RESULTS: The postoperative PFC was more than its preoperative-value in 80.39%
      TKAs. Patients who had increased postoperative PFC had significantly less
      preoperative AFO. Female patients in our study had significantly less
      preoperative AFO compared to males. Thus, we deduced that female patients with
      lesser preoperative AFO undergoing TKA had increased postoperative PFC than male
      patients. PFC not only accounted for the overstuffing of the PFJ because of the
      patellar component, but also because of the femoral component; thus was a better
      measure of PFJ overstuffing compared to isolated PT. Passive knee ROM in the
      postoperative TKA patients approximately decreased by 2 degrees for every 1 mm
      increase in PFC compared to its preoperative-value in the patients with PFJ
      overstuffing. CONCLUSION: We conclude that overstuffing of the PFJ in
      postoperative TKA is present in 80.39% patients. Higher chances of postoperative
      PFJ over stuffing are present in female patients and those with thinner anterior
      cortex of distal femur. Postoperative passive knee ROM decreases significantly in
      patients with postoperative PFJ overstuffing (Every 1 mm increase in the
      postoperative PFC, passive knee ROM decreased by approximately 2 degrees).

PMID- 28511466
TI  - Management of Cubitus Varus Deformity in Children by Closed Dome Osteotomy.
AB  - INTRODUCTION: Supracondylar fractures are the most common elbow injuries in
      skeletally immature children between 5-10 years of age and cubitus varus
      deformity is the most common late complication. Cubitus varus or bow elbow or
      gunstock deformity is the result of malunion occurring as a complication of
      supracondylar fracture of the humerus. Various type of corrective osteotomies are
      used of which lateral closed wedge French osteotomy is commomly used which has
      its own complications like lateral condylar prominence, unsightful scar and
      limitation of movement. Closed dome osteotomy is a technique which overcomes
      these complications. This surgery is done with simple readily available
      instruments in the orthopaedic operation theatre with no special requirements for
      instrumentation. AIM: This study was done to study the results of closed dome
      osteotomy for correction of cubitus varus deformity, after malunited
      supracondylar fracture of humerus in children. MATERIALS AND METHODS: This study
      included 25 children of either sex with malunited supracondylar fracture of
      distal humerus having cubitus varus deformity admitted in orthopaedics
      department. After appropriate pre operative assessment, closed dome osteotomy was
      done and post operatively X-ray of patients was taken and carrying angle and
      Lateral Condylar Prominence Index (LCPI) were calculated. Patients were re
      assessed at complete union and results were calculated as per Mitchell and Adams
      criteria. RESULTS: In our study of 25 patients, 68% were males, 32% were females.
      Majority (84%) of patients were in the age group of 5-10 years. Carrying angle
      post operatively was 0-10 degrees  valgus in 64% of patients while 36% had 10-20
      degrees  valgus. LCPI changed post operatively ranging from +5.0% to -10.7%,
      average -2.75%. Decrease in LCPI had better cosmetic appearance. Range of motion
      post operatively increased or remained same as previous full motion in 84% of the
      patients. Union occurred in all patients by eight weeks. Few complications were
      seen. Results according to Mitchell and Adams criteria were excellent in 88% and
      good in 12%; while no poor results were recorded. CONCLUSION: The results
      obtained in our study concluded that closed dome osteotomy is safe and effective
      treatment for the correction of cubitus varus deformity with few minor
      complications.

PMID- 28511467
TI  - Chaput Tubercle Fracture in an Adult- A Rare Case Report.
AB  - Chaput tubercle fracture occurs at the antero-lateral position of the distal
      tibia in adult as a counterpart of adolescent Tillaux fracture. It is a case of
      adult male which presented to us with onset of acute pain, swelling and
      restricted movements of ankle after a road side accident. A clinical diagnosis of
      Chaput tubercle fracture was established after a CT-scan. The displaced fracture
      was managed by open reduction and internal fixation by screw. At the end of
      follow up, the foot and ankle ability score measured. Through this case report we
      convey that Chaput tubercle fracture in an adult is a rare entity.

PMID- 28511468
TI  - Tuberculosis of Acromioclavicular Joint.
AB  - Tuberculosis (TB) arthritis accounts for approximately 1%-3% of all cases of TB
      and for approximately 10%-11% of extra pulmonary cases. Isolated
      acromioclavicular joint TB has been reported rarely with varied presentations as
      case series of one to three cases none of them being large studies. In our case,
      patient presented with pain in left shoulder since one month. Patient was
      investigated and was diagnosed to have acromioclavicular joint TB on basis of
      positive Acid Fast Bacilli (AFB) stain and cytology. Patient recovered well with
      antitubercular therapy. Thus, it is important to send Ziehl-Neelsen (ZN) stain in
      all cases in an endemic country like India.

PMID- 28511469
TI  - Clinical Profile and Outcome of Newborns with Acute Kidney Injury in a Level 3
      Neonatal Unit in Western India.
AB  - INTRODUCTION: Acute Kidney Injury (AKI) is a serious condition in neonatal care.
      It complicates the management necessitating the restrictive use of medications.
      AIM: To evaluate clinical profile, identify associated and prog-nostic factors in
      newborns with AKI. MATERIALS AND METHODS: This was a case control study done
      between January 2008 to January 2010. Total 1745 newborns were admitted, of which
      74 babies had AKI. It was defined as serum creatinine >1.5mg/dl. Control group
      was selected randomly from the hospital numbers of the newborns derived from the
      electronic registry with serum creatinine below 1.5 mg/dl. Demographic variables
      like birth weight, gender, gestational age, admission age, growth restriction,
      Apgar scores, electrolyte levels; and common clinical conditions like asphyxia,
      sepsis, meningitis, persistent pulmonary hypertension, Necrotizing Enterocolitis
      (NEC), mechanical ventilation, congenital heart disease; were compared amongst
      the two groups. Information was obtained from the admission register, admission
      files, labor register of obstetrics and gynaecology department and electronic
      registry. Chi square/independent sample t-test as applicable and logistic
      regression were used to establish an association of various factors and outcome
      with AKI. RESULTS: The incidence of AKI in our study was 4.24%. Demographic
      variables more common in AKI group were inborn (p=0.011), male gender (p=0.032),
      term gestation (p=0.001), Appropriate for gestational age (0.001), higher birth
      weight (p<0.001), full term (p<0.001), sepsis (p<0.001), NEC (p=0.042), low ApGAR
      scores at one minute (p=0.011) and five minute (p=0.003). However, on
      multivariate logistic regression only male gender [Odds Radio (OR)=2.84,
      Confidence Interval (CI)=1.12-7.21] and Sepsis (OR=14.46, CI=4.5-46.46) were
      associated with AKI. Respiratory distress syndrome was more prevalent in the
      control group (p<0.003). No need of mechanical ventilation and absence of shock,
      improved the survival. CONCLUSIONS: AKI continues to be of clinical significance
      in neonatal intensive care. Further studies are needed to evaluate newer
      associations (like male gender and low APGAR scores).

PMID- 28511470
TI  - Study on Steroid Induced Ocular Findings in Children with Nephrotic Syndrome.
AB  - INTRODUCTION: Long term use of corticosteroids in Nephrotic Syndrome (NS) is
      associated with ocular complications such as Posterior Subcapsular Cataract
      (PSC), glaucoma, increased intra-ocular pressure, ptosis, mydriasis, eyelid skin
      atrophy, keratisis, thinning of cornea and sclera, repeated hordeolum
      exacerbations. AIM: To determine ocular abnormalities in children with NS and
      their association with steroid dosing and duration. MATERIALS AND METHODS:
      Hundred patients with NS in the age group of 2-18 years, with no evidence of
      other systemic disease, were considered for the study. Group I included cases
      (66) who took standard steroid regimen for first episode of NS. Group II included
      cases (34) who took steroid irrationally (daily basis for long time) other than
      standard regimen. Steroid induced ocular complications were compared in both
      groups after detailed ophthalmological examination. Statistical analysis was done
      using Statistical Package for Social Science (SPSS-20.0). RESULTS: Ocular
      abnormalities were found in 12 patients out of 66 in Group I (18%) and 16
      patients out of 34 patients in Group II (47%). Out of 12 patients of Group I who
      had ocular problems, three had myopic astigmatism, eight patients had PSC and one
      had temporal disc pallor. While in Group II, out of 16 patients who had ocular
      complications, two patients had raised intra ocular pressure and two patients had
      myopic astigmatism and 12 patients had posterior sub capsular cataract. The
      difference in mean cumulative steroid doses in both groups was statistically
      significant but no such difference was there between duration of steroid intake
      in both group. CONCLUSION: Our study concluded that ocular complications were
      more common in patients with irrationally steroid intake and cumulative steroid
      dose intake was also significantly higher in same patients.

PMID- 28511471
TI  - Internet Based Obesity Prevention Program for Thai School Children- A Randomized
      Control Trial.
AB  - INTRODUCTION: Internet based obesity prevention program is one approach in
      learning strategies to improve healthy behaviour. It has been advocated as one
      strategy to address the rising prevalence of childhood obesity; however, their
      efficacy is not seen consistently. AIM: The purpose of this study was to assess
      the efficacy of internet based obesity prevention program in Thai school
      children. MATERIALS AND METHODS: Healthy children studying in public schools in
      one township of central Thailand were randomly assigned to either the
      intervention (internet based) program or the control group. Anthropometric
      characteristics were recorded at baseline and for the next four following months
      at monthly intervals. Changes in the percentage of overweight/obese children and
      changes in BMI at the end of study were considered as the primary and secondary
      outcome, respectively. RESULTS: A total of 217 children, mean age of 10.7 years,
      were included into the final analysis. Baseline anthropometric parameters and
      percentages of overweight/obesity were not significantly different between
      groups. At the end of the study, the control group had a higher percentage of
      overweight/obesity than the intervention group (56.6% vs. 39.6%, respectively; p
      value=0.009). Children in the control group had a significantly higher increase
      in net BMI gains than those in the intervention group (1.24kg/m2 vs. 0.40kg/m2, p
      value=0.027). The intervention group had no changes in BMI z-score (-0.001, 95%CI
      -0.19 to 0.18, p-value=0.988), contrary to those in the control group, which had
      significant gain of BMI z-score at the end of study (0.45, 95%CI 0.27 to 0.63, p
      value<0.001). CONCLUSION: Internet the based obesity prevention program was
      effective in modifying anthropometric outcome and helped to address the rising
      prevalence of overweight and obese status in Thai children.

PMID- 28511472
TI  - Short Term Unscheduled Revisits to Paediatric Emergency Department - A Six Year
      Data.
AB  - INTRODUCTION: Reviewing the reasons for return visits within 24 hours is a very
      important method of determining possible problems of emergency health care.
      Several causes stay behind unscheduled emergency return visits. Therefore,
      identifying these factors is crucial to set strategies in order to decrease the
      number of unnecessary visits. AIM: To define the characteristics of the patients
      returning to the Paediatric Emergency Department (PED) within 24 hours via
      determining rate, number and demographic data of patients. MATERIALS AND METHODS:
      The present study design involves retrospective data collection of patients who
      returned to PED within 24 hours after being discharged. Data was included over
      six year period and was collected from July 1, 2010 to June 30, 2016. The data
      was analysed with SPSS17.0 statistical package for windows. RESULTS: A total of
      1994 patients returned to PED within 24 hours from July 1, 2010 to June 30, 2016.
      The most common group of revisiting patients were toddlers (aged 0-2-year old),
      n=1168 (58.5%), and the least number represented young adolescents (aged 15-18
      year old), n=82 (4.1%). Number of patients returning to PED in 24 hours has
      significantly increased within years from approximately 90 patients to 720
      (p<0.05). This increase in number was observed in all and each age group (from 0
      18 years of age) without any exception. Seasonal distribution of the patients
      showed no significant difference (p>0.05) for each age, but again, presented
      definite negative correlation with age (the older is the patient group, the less
      is the number of revisits). The most common time for revisits was 17-24 hours
      after first discharge from PED, n=1277 (64.04%). CONCLUSION: The number of return
      visits is increasing over the years. The younger the patient is, more likely is
      the risk of unscheduled revisit to PED. Most of the patients returned to PED in
      17 to 24 hours after discharge.

PMID- 28511474
TI  - Correspondence: Predictors of Mortality in Paediatric Myocarditis.

PMID- 28511473
TI  - Phytotherapy with Hordeum Vulgare: A Randomized Controlled Trial on Infants with
      Jaundice.
AB  - INTRODUCTION: Jaundice is one of the most common causes of admission to hospital
      in newborns which is often associated with several complications. AIM: The
      present study was conducted to evaluate the effect of H. vulgare in reducing
      jaundice. MATERIALS AND METHODS: In this double-blind, randomized controlled
      trials 70 term infants hospitalized due to jaundice in 2014 were enrolled.
      Control group was treated with full-time phototherapy alone using LED except when
      the infants were breastfed and case group with phototherapy, as per the protocol
      in the control group, along with and topical H. vulgare seed flour three times a
      day. Data were analysed using and analysis of covariance (ANCOVA) and paired t
      test in SPSS version 16.0. RESULTS: There was a significant difference in mean
      indirect bilirubin level between the two groups p<0.05, such that the mean
      indirect bilirubin level was higher in the control group. Furthermore, no
      significant difference was seen in direct bilirubin level between the two groups
      at discharge p>0.05. CONCLUSION: H. vulgare flour can cause decrease in indirect
      bilirubin. Because the rate of decrease in indirect bilirubin can be effective in
      preventing severe complications due to bilirubinemia, H. vulgare can be used as a
      complementary therapy to treat jaundice.

PMID- 28511475
TI  - Colour Doppler Evaluation of Extracranial Carotid Artery in Patients Presenting
      with Acute Ischemic Stroke and Correlation with Various Risk Factors.
AB  - INTRODUCTION: Stroke is defined as an abrupt onset of neurologic deficit due to
      vascular cause. It is one of the leading causes of mortality and morbidity all
      over the world making early diagnosis and treatment inevitable. Lesions of extra
      cranial carotid arteries are implicated in majority of cases of acute ischemic
      stroke. Carotid Doppler is a non-invasive imaging technique, with sensitivity
      approaching that of angiography. Computed Tomography (CT) plays a major role to
      assess the site and nature of the lesion in patients with acute ischemic stroke.
      AIM: To evaluate the role of carotid Doppler sonography in patients presenting
      with acute ischemic stroke and find association between carotid artery stenosis
      and risk factors such as diabetes mellitus, hypertension, hyperlipidemia, smoking
      and age. MATERIALS AND METHODS: The present study was conducted on 50 patients.
      CT scan was done to diagnose acute ischemic stroke in patients who presented to
      emergency medicine with symptoms of acute ischemic stroke. Retrospectively CIMT
      and plaque characterization were done by gray scale ultrasound. Site and severity
      of stenosis were assessed on colour Doppler. All these findings were correlated
      with clinical presentation and risk factors. The collected data was statistically
      analyzed and multivariant logistic regression (R-value) test of significance was
      applied by using SPSS 16.0 version software. RESULTS: On carotid Doppler, ICA/CCA
      PSV ratio was good predictor of stenosis and ratio above three indicates
      significant stenosis (>60%). Carotid bulb was most common location of plaque
      formation. Hypertension and diabetes were the most prevalent risk factors for
      cerebral ischemic stroke. Out of total 50 patients, 32 had hypertension (64%) and
      22 had diabetes (44%). Hypertension and hyperlipidemia showed maximum mean R
      values (0.275 and 0.048 respectively) and positive correlation with stenosis and
      increased CIMT in acute ischemic stroke patients. CONCLUSION: The present study
      highlights the importance of Doppler sonography in acute ischemic stroke patients
      through surveillance of atherosclerosis.

PMID- 28511476
TI  - Magnetic Resonance Imaging in Mixed Mullerian Tumour: Report of Two Cases.
AB  - Malignant Mixed Mullerian Tumours (MMMTs) or carcinosarcomas of uterus are rare
      aggressive tumours of mesenchymal origin. It is associated with high incidence of
      lymphatic, pulmonary and peritoneal metastasis. We hereby present two cases of
      mixed mullerian tumour. Case-1 was a 60-year-old post menopausal woman who had
      come with complaint of metrorrhagia and a protruding mass in the vagina. Case-2
      was of a 54-year-old post-menopausal woman who came with complaints of heavy
      vaginal bleeding, pelvic pain since two months. For the assessment of these
      tumours Magnetic Resonance Imaging (MRI) is preferred imaging modality due to
      excellent tissue contrast to detect the myometrial invasion, local extent and
      staging. Preoperative differentiation of mullerian tumour with endometrial
      carcinoma is important as both have different treatment.

PMID- 28511477
TI  - Inferior Vena Cava Agenesis: A Rare Cause of Pelvic Congestion Syndrome.
AB  - Complete absence of Inferior Vena Cava (IVC) is a rare anomaly with a reported
      incidence of 0.0005% to 1%. This is often asymptomatic with incidental detection
      during cross-sectional imaging. It may also present with deep venous thrombosis,
      pulmonary thromboembolism or compressive symptoms in form of nerve root
      compression. Pelvic Congestion Syndrome (PCS) is an increasingly recognized
      entity with well laid out diagnostic criteria and evolving management protocols.
      Complete absence of IVC is a rare cause of pelvic congestion syndrome. We present
      a case of young female presenting with symptoms typical of pelvic venous
      congestion who was found to have complete absence of IVC as the underlying cause.
      She also had associated small left kidney with compensatory hypertrophy of the
      right kidney which is another rare association.

PMID- 28511478
TI  - Recognition of Small Airways Obstruction in Asthma and COPD - The Road Less
      Travelled.
AB  - The small airways, once regarded as the silent zone in the air conducting system
      of the lungs are now known to be one of the initial sites of involvement in
      diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD).
      Identification of the involvement of distal airways in these diseases is often
      difficult to assess, clinically as well as by conventional pulmonary function
      tests and therefore, usually remains undiscovered in early stages. Early
      recognition of their involvement in asthma and COPD and timely management may
      reduce long term morbidity in these conditions. This article aims to highlight
      the relatively lesser recognized facts about small airways involvement in asthma
      and COPD and role of imaging and newer modalities for detection.

PMID- 28511479
TI  - Extramedullary Haematopoiesis Presenting as an Adrenal Mass.

PMID- 28511480
TI  - Azygos Lobe - A Rare Anatomical Variant.

PMID- 28511481
TI  - Relationship of on Admission Hypocalcaemia and Illness Severity as Measured by
      APACHE-II and SOFA Score in Intensive Care Patients'.
AB  - INTRODUCTION: Hypocalcaemia is very much prevalent in critically ill patients yet
      very less is known about its association with severity of illness. Acute
      Physiology and Chronic Health Evaluation (APACHE) and Sequential Organ Failure
      Assessment (SOFA) are two commonly used and validated scoring tool used to assess
      the severity of illness in critically ill patients. AIM: To analyze the relation
      of on admission hypocalcaemia with severity of illness as measured by APACHE-II
      and SOFA scores. MATERIALS AND METHODS: After institute approval, 111 patients
      admitted during May to June 2016 were evaluated. Age, sex, on admission, ionized
      calcium (iCa0) levels, first day APACHE-II and SOFA scores were collected. Data
      were then divided in different classes based on iCa0 levels (i.e.,
      normocalcaemic, mild, moderate and severe hypocalcaemic), APACHE-II and SOFA
      scores and their relationship was assessed using INSTAT software (GraphPad
      Software, Inc, La Zolla, CA, USA) with appropriate statistical tests. RESULTS:
      Seventy eight (70.27%) patients were having hypocalcaemia on admission (<1.15
      mmol/L). The mean APACHE-II score of normocalcaemic patients were significantly
      (p<0.05) lower as compared to moderate and severe hypocalcaemic patients (15.57+/
      6.85 versus 21.72+/-6.37 and 15.57+/-6.85 versus 22.34+/-7.53, respectively). The
      mean iCa0 level in patients with APACHE-II > 20 were significantly lower than
      patients with APACHE-II < 9 (0.88+/-0.26 versus 1.09+/-0.24, p <0.05) but the
      mean iCa0 level in patients with SOFA > 9 were not significantly lower than
      patients with SOFA < 4 (0.99+/-0.41 versus 1.04+/-0.23, p > 0.05). The relative
      risk of on admission hypocalcaemia across increasing illness severity was also
      not statistically significant. Both relative risk of mortality and length of ICU
      stay were higher in on admission moderate hypocalcaemic patients as compared to
      normocalcaemic but the difference was not statistically significant. CONCLUSION:
      On admission, hypocalcaemia has inconsistent correlation with increasing illness
      severity in adult intensive care patients. iCa0 of 0.81-0.90 mmol/L appears to
      have maximum deleterious effect with regard to mortality and length of ICU stay.

PMID- 28511482
TI  - Effect of Ketofol on Pain and Complication after Caesarean Delivery under Spinal
      Anaesthesia: A Randomized Double-blind Clinical Trial.
AB  - INTRODUCTION: Pain is the key concern of women after caesarean delivery that may
      interfere with breastfeeding. AIM: The aim of this study was to assess effect of
      ketofol (ketamine/propofol combination) on pain and complication after caesarean
      delivery under spinal anaesthesia. MATERIALS AND METHODS: In this randomized
      double-blind clinical trial, 92 parturient scheduled for elective caesarean
      delivery under spinal anaesthesia were included. The simple random sampling
      method was used to place subjects in four groups of ketamine (0.25 mg/kg),
      propofol (0.25 mg/kg), ketofol (25 mg ketamine plus 25 mg propofol) and placebo
      (saline). The drugs were administered intravenously immediately after clamping
      the umbilical cord. Visual Analog Scale (VAS) was used to determine the intensity
      of pain. Complications after surgery including shivering, nausea and vomiting as
      well as onset of breastfeeding were recorded. RESULTS: The mean score of pain,
      morphine consumption and time of breastfeeding in the ketofol group were
      significantly lower than other groups at various intervals (p<0.05, p<0.001). The
      frequencies of shivering, nausea, vomiting, retention and pruritus in the ketofol
      group were significantly lower than other groups (p<0.001, p<0.05). CONCLUSION:
      The effective role of ketofol on reducing pain and complication after caesarean
      delivery indicated that it can be considered as a safe and alternative drug in
      these patients.

PMID- 28511483
TI  - A Study of Morbidity and Cost of Peripheral Venous Cannulation in Neonates
      Admitted to Paediatric Surgical Intensive Care Unit.
AB  - INTRODUCTION: Peripheral venous access in sick neonates is indicated for
      administration of fluids, drugs or nutrients. AIM: We conducted an audit of
      peripheral venous access in neonates admitted to paediatric surgical intensive
      care unit to study the morbidity, time spent on cannulation and cost with its
      use. MATERIALS AND METHODS: One hundred consecutive neonates requiring hospital
      admission to paediatric surgical intensive care unit in a period of one year were
      included in the study. Peripheral venous access was secured in all patients. We
      conducted an audit for the number of venipuncture sites, wastage of cannulae,
      cost, time spent on cannulation and morbidity with its use. Neonates were divided
      into three groups depending on their surgical intervention. Namely, Group A
      (thoracic procedures), Group B (bowel surgery) and Group C (other surgery and non
      operative cases). RESULTS: In Group A, mean venepuncture sites were 10.66, used
      cannulae were 5.6, wasted cannulae were 4.3, total cost of cannulation was 870
      rupees and 93.78 minutes were spent in cannulation per neonate. In Group B, mean
      venepuncture sites were 7.58, used cannulae were 4.35, wasted cannulae were 2.59,
      total cost of cannulation was 603 rupees and 59.85 minutes were spent in
      cannulation per neonate. In Group C mean venepuncture sites were 2.78, used
      cannulae were 2.9, wasted cannulae were 0.57, total cost of cannulation was 232
      rupees and 26.51 minutes were spent in cannulation per neonate. Thrombophlebitis
      severity was greater in neonates who had longer ICU stay and ventilator dependent
      days. CONCLUSION: Peripheral venous cannulation of longer duration is costly,
      time consuming, and associated with significant neonatal morbidity. It may be
      worthwhile to consider alternative vascular devices such as peripherally inserted
      central catheters or central venous catheters in such situations.

PMID- 28511484
TI  - Efficacy of Structured Yoga Intervention for Sleep, Gastrointestinal and
      Behaviour Problems of ASD Children: An Exploratory Study.
AB  - INTRODUCTION: Autism Spectrum Disorder (ASD) is a neuro developmental disorder
      which appears at early childhood age between 18 and 36 months. Apart from
      behaviour problems ASD children also suffer from sleep and Gastrointestinal (GI)
      problems. Major behaviour problems of ASD children are lack of social
      communication and interaction, less attention span, repetitive and restrictive
      behaviour, lack of eye to eye contact, aggressive and self-injurious behaviours,
      sensory integration problems, motor problems, deficiency in academic activities,
      anxiety and depression etc. Our hypothesis is that structured yoga intervention
      will brings significant changes in the problems of ASD children. AIM: The aim of
      this study was to find out efficacy of structured yoga intervention for sleep
      problems, gastrointestinal problems and behaviour problems of ASD children.
      MATERIALS AND METHODS: It was an exploratory study with pre-test and post-test
      control design. Three sets of questionnaires having 61 questions developed by
      researchers were used to collect data pre and post yoga intervention.
      Questionnaires were based on three problematic areas of ASD children as mentioned
      above and were administered to parents by teachers under the supervision of
      researcher and clinical psychologists. Experimental group was given yoga
      intervention for a period of 90 days and control group continued with school
      curriculum. RESULTS: Both children and parents participated in this intervention.
      Significant changes were seen post yoga intervention in three areas of problems
      as mentioned above. Statistical analysis also showed significance value of 0.001
      in the result. CONCLUSION: Structured yoga intervention can be conducted for a
      large group of ASD children with parent's involvement. Yoga can be used as
      alternative therapy to reduce the severity of symptoms of ASD children.

PMID- 28511485
TI  - Spiritual Well-Being and Associated Factors with Relapse in Opioid Addicts.
AB  - INTRODUCTION: Opioid dependence relapse is a complex and multidimensional
      problem, and lack of spiritual well-being is a major concern in opioid addicts.
      AIM: This study was conducted to determine spiritual well-being and factors
      associated with relapse among opioid addicts. MATERIALS AND METHODS: This cross
      sectional study was conducted from April 2015 to September 2015. According to
      purposive sampling, 312 eligible addicted patients were enrolled in the study.
      The patients had at least an attempt of detoxification in the past six months and
      referred to an outpatient detoxification clinic in Shahrekord (Southwest, Iran).
      They completed Paloutzian and Ellison's Spiritual Well-being Scale. A researcher
      developed questionnaire consisting of demographic characteristics and 20
      questions about associated factors with relapse was administered. Data were
      analysed by version 16.0 (SPSS Inc.,Chicago, IL) using one-way ANOVA, Pearson's
      correlation test, chi-square, Friedman test, and student's t-test. RESULTS: The
      most important factors associated with opioid dependence relapse consist of
      relation with an addict friend, unemployment, living expenses, family conflicts,
      and somatic pain. In the present study, 157 patients had never experienced
      relapse while the mean of relapse in the rest participants was (3.25+/-1.53)
      times. Furthermore, the addicted patients with relapse had significantly lower
      scores of spiritual well-being and its subscales compared with non-relapse
      patients (p<0.001). CONCLUSION: The findings of the present study indicate the
      necessity of paying attention to spiritual well-being, family and economical,
      personal, and occupational factors as crucial factors in opiate addiction
      relapse.

PMID- 28511486
TI  - A Review on Detection and Treatment Methods of Sleep Apnea.
AB  - This paper presents a review on detection and treatment methods of sleep apnea.
      Sleep apnea is the most common type of breathing-related sleep disorder. It
      manifests in a variety of behaviours from teeth grinding to night terrors as
      involuntary night-time events. The most common sleep disorders are narcolepsy,
      hypersomnia, sleep talking, sleep walking, and bedwetting. Sleep apnea
      (somnipathy) is a serious sleep disorder that pauses breathing while sleeping.
      Breathing pauses occur 30 times or more during sleep and it lasts for few seconds
      to minutes, when normal breathing starts after this pause. Untreated sleep apnea
      patients stop breathing, which happens up to hundreds of times during sleep that
      ultimately results in atrial fibrillation, cardiac arousal, stroke, brain tumor
      and other vascular diseases at the age of 65 that causes death. Smokers are at a
      greater threat for sleep apnea. Several studies have suggested that a person who
      smokes more than two packs a day has 40 times the risk of sleep apnea then
      nonsmokers. This review includes the discussion about detection of sleep apnea
      from heart rate and respiratory events. The published literature of sleep apnea
      and methods of treatment are also discussed.

PMID- 28511487
TI  - A Comparative Study of Liquid Nitrogen Cryotherapy as Monotherapy versus in
      Combination with Podophyllin in the Treatment of Condyloma Acuminata.
AB  - INTRODUCTION: Condyloma Acuminata (CA) is a common viral sexually transmitted
      disease. Although various treatment modalities are available for treating CA, but
      none of them can achieve 100% response rate. In a search for better response rate
      and less recurrence rate, the combination of cytotoxic agent Podophyllin with
      ablative liquid nitrogen cryotherapy was evaluated over cryotherapy alone. AIM:
      To evaluate the synergistic effect of Podophyllin as a chemotherapeutic adjunct
      to an ablative therapy of liquid nitrogen cryotherapy versus liquid nitrogen
      cryotherapy alone in the treatment of CA. MATERIALS AND METHODS: Sixty patients
      with multiple CA were randomly assigned to two groups in the study. Thirty
      patients in group A received double freeze thaw cycle of 25 seconds of liquid
      nitrogen cryotherapy. Thirty patients in Group B were subjected to liquid
      nitrogen cryotherapy in a similar manner followed by application of not more than
      0.5 ml of 25% Podophyllin solution. All patients were followed up at 1, 4, 8, 12
      and 24 weeks after the treatment to monitor the response to therapy and
      evaluation for any recurrence. When the number of unresponsive lesions were more
      than 30% of original lesions at 4 weeks follow-up, then the whole procedure was
      repeated again. RESULTS: The complete response rate and the recurrence rate in
      the Group B in our study were comparable to Group A as the difference was
      statistically insignificant. But the differentiating point was that the similar
      results were obtained in Group B with an average1.2 sessions per patient in
      comparison to an average of 1.67 sessions per patient in Group A. CONCLUSION:
      Cryotherapy represents a simple, safe and effective regimen for the treatment of
      multiple CA which in combination with Podophyllin is even more effective as a
      single session procedure; thereby shortening the treatment regimen.

PMID- 28511489
TI  - Micronucleus Assay in Urothelial Cells in Cancer Cervix.
AB  - INTRODUCTION: Cancer ranks third among the ten leading global causes of death. To
      evaluate the genotoxic risks, observed as DNA damages, can be assessed by
      Micronucleus (MN) test. AIM: To identify the occurrence of MN in normal and
      cancer cervix and find the correlation between MN and stage of cancer. MATERIALS
      AND METHODS: A total of 60 females were included in the study and visual
      examination of the cervix was done. Based on the examination two groups were
      formed: A- Normal cervix (n-23) and B- Presence of erosion or growth or ulcer
      etc., in cervix (n-37). Midstream urine sample was collected and centrifuged from
      the cases after getting the informed consent. Slides were prepared from the
      pellet, were fixed in methanol, glacial acetic acid fixative and stained with
      Giemsa and May Grunwald stain. Statistical analysis was done by student's t-test
      and chi-square test. RESULTS: A linear association was noted between the mean MN
      count and cancer cervix stage. Almost 18.2% of the Group A cases had significant
      MN count. Sensitivity and specificity of MN count in Group A was 83.8% and 82.6%
      respectively. The efficiency was 83.3%. CONCLUSION: A statistically significant
      MN count was seen in the different stages of cancer cervix. There are cases who
      had normal findings on visual inspection of cervix but with significant MN count
      are prone for malignant transformation. MN assay is an easy, non-invasive, cost
      effective method and can be used as a screening test for a large population.

PMID- 28511488
TI  - Comparative Efficacy and Safety of Ebastine 20 mg, Ebastine 10 mg and
      Levocetirizine 5 mg in Acute Urticaria.
AB  - INTRODUCTION: Acute and chronic urticaria can result in severely impaired quality
      of life from pruritus and associated sleep lessness, as well as anxiety and
      depression. Various treatment modalities are available out of which second
      generation non sedating H1 antihistamines e.g., fexofenadine, loratidine,
      desloratadine, cetirizine, levocetirizine, ebastine etc., are used as the first
      line treatment. AIM: To compare the safety and efficacy of ebastine 20 mg,
      ebastine 10 mg and levocetirizine 5 mg in the patients of urticaria. MATERIALS
      AND METHODS: A longitudinal study was conducted in dermatology Outpatient
      Department (OPD) of Adesh Institute of Medical Sciences and Research, Bathinda,
      India. A total of 150 patients between the age group 10-70 years, both men and
      women having urticaria were enrolled and divided into three groups of 50 each.
      Group A was given ebastine 20 mg OD, Group B was given ebastine 10 mg OD and
      Group C was given levocetirizine 5 mg OD. The patients were asked to scale their
      severity of disease over a period of follow up based on Urticarial Activity Score
      7 (UAS7). RESULTS: The mean age of patients was 32.82 years. The mean UAS 7 score
      at the end of 4th week was 1.08 with ebastine 20 mg, 1.98 with levocetirizine 5
      mg and 3.98 with ebastine 10 mg. In group A, 40 out of 50 patients (i.e., 80%),
      in Group B 25 out of 50 (i.e., 50%) get UAS7=0 and in Group C, 35 (i.e., 70%)
      patients who got relieved of symptoms at the end of treatment. When the scores
      were redefined and categorized under relieved and not relieved, and comparison
      done between all three groups, then there was a significant difference in the
      number of patients getting relieved, with p<0.001 (highly significant).
      Levocetirizine 5 mg had shown more side effects like dryness of mouth and
      sedation as compare to ebastine irrespective of dosage. The comparison made
      between the number of patients developing side effects among the groups was
      highly significant (p<0.001) for all the side effects. CONCLUSION: Ebastine 20 mg
      is found to have superior efficacy for treatment of Urticaria as compared to
      ebastine 10 mg but with levocetirizine 5 mg the results were almost similar.
      Tolerability of ebastine 20 mg is similar to ebastine 10 mg but with
      levocetirizine 5 mg there were more side effects and less tolerability.

PMID- 28511490
TI  - Primary Orbital Follicular Lymphoma: A Case Report and Review.
AB  - Orbital Lymphomas (OL) constitute a heterogeneous group of lymphoproliferative
      disorders of the orbit. They are predominantly of the Mucosa-Associated Lymphoid
      Tissue (MALT) subtype. Radiotherapy is the mainstay of treatment in localized
      orbital tumours, while chemotherapy is reserved for systemic disease. Authors
      report a case of a primary orbital lymphoma of follicular subtype (stage 1E) in a
      54-year-old female managed by surgery and adjuvant radiotherapy.

PMID- 28511491
TI  - Choroidal Metastasis as Initial Presentation in Adenocarcinoma of Lung: A Case
      Report.
AB  - Vision impairment as an initial presentation detecting choroid metastasis in
      primary lung cancer is rare. Prevention or treatment of visual loss and
      improvement in quality of life can be achieved by treatment of intraocular
      metastasis. The survival of the patient in choroid metastasis with lung primary
      is poor with the median survival being 3.3 months. However, proper treatment may
      increase the quality of life and survival to an extent. We report a case of
      adenocarcinoma of lung in a female patient, presented initially with visual
      impairment as a result of choroidal metastasis and treated with external beam
      radiotherapy for choroidal metastasis followed by palliative chemotherapy. The
      patient was survived with improved vision and quality of life since last 12
      months of diagnosis.

PMID- 28511492
TI  - Cardiac Myeloid Sarcoma: Review of Literature.
AB  - Granulocytic Sarcomas (GS) also called as Myeloid Sarcomas (MS) or chloromas are
      the representatives of extramedullary infiltrates of immature myeloid cells
      including myeloblasts, promyelocytes and myelocytes. Primary cardiac malignancies
      per se are rare and infiltration of cardiac muscles by secondary malignant cells
      is also an uncommon finding. Out of these cardiac tumors, contribution of Cardiac
      Myeloid Sarcoma (CMS) is even more smaller thereby limiting our knowledge about
      this rare entity. Because of its very lower incidence, an exact guideline for
      diagnosis and management is still missing and usually haematologists around the
      world are treating CMS based on their clinical acumen. Aim of this review is to
      briefly discuss the presenting clinical feature, differential diagnosis,
      diagnostic workup and management based on published articles related to CMS till
      date.

PMID- 28511493
TI  - Isolated Central Nervous System (CNS) Relapse in Paediatric Acute Promyelocytic
      Leukaemia: A Systematic Review.
AB  - INTRODUCTION: Extramedullary disease, as a whole, is rare in Acute Promyelocytic
      Leukaemia (APML). If at all relapse occurs, following sites are involved: Central
      Nervous System (CNS), skin, testes, mediastinum, gingiva, and ear. Isolated CNS
      relapses after complete morphological and molecular remission is rarer
      particularly in children. AIM: To review the literature systematically to find
      out the incidence of isolated CNS relapse in paediatric APML cases. MATERIALS AND
      METHODS: A systematic search of major databases (Medline, Pubmed and Google
      Scholar) was conducted. We included all types of studies that reported about
      incidence or prevalence of isolated CNS relapse in children upto 18 years of age
      with APML. RESULTS: A total of nine studies (with 10 cases of isolated CNS
      relapse) were included. Majority (70%) was high risk patients, and 60% were <=six
      year-old. Nearly, 50% were having the mean time to relapse <12 months and most
      (60%) of them were male. The children who died were having shorter time to CNS
      relapse (around 12 months), and were older (>6 to 18 years). CONCLUSION: In the
      present review, disease in the high-risk group, male sex, younger age (<=six
      years-old), and Promyelocytic Leukaemia/Retinoic Acid Receptor Alpha (PML-RARA)
      detection was found to be associated with isolated CNS relapse in children with
      APML. Cerebrospinal fluid (CSF) examination along with immunophenotyping and
      Reverse Transcription polymerase Chain Reaction (RT-PCR) for PML-RARA is required
      for a definite diagnosis and early treatment of patients to improve overall
      survival.

PMID- 28511494
TI  - Eyelid Malignancies- Always Quite Challenging.
AB  - The diagnosis and management of eyelid cancers are quite challenging. Eyelid
      tumours are relatively rare diverse group of diseases varied in their
      presentation and extent. Many benign tumours and inflammatory conditions quite
      frequently masquerade eyelid cancers. Eyelid cancers are not single entity but
      comprise a wide range of tumours with extremes of tumour biology from indolent to
      very aggressive histopathologic types. Compromise on aesthetics and eyelids'
      indispensable function of protecting the eyes during management, may lead to
      untoward cosmetic disfigurement and loss of vision. On the other hand, inadequate
      cancer clearance will also be vision threatening and life threatening due to loco
      regional recurrence and metastasis. To strike an optimal balance is a challenging
      task, to achieve 'cancer cure' with maximum preservation of function and
      cosmetics. In addition, the integration of other modalities of treatment,
      judicious selection and their sequencing require multidisciplinary discussion and
      joint management by different specialists. We are presenting four case scenarios,
      we met with in our teaching hospital with reference to literature review to
      emphasize that eyelid malignancies are not always simple with respect to
      diagnosis and management.

PMID- 28511495
TI  - Barriers Encountered by Accredited Social Health Activists (ASHA) in Arthritis
      Rehabilitation: A Qualitative Study.
AB  - INTRODUCTION: Healthy behaviour through education of individuals with arthritis
      is the mainstay of long term management. Time and access constraints restrict
      medical professionals from active involvement in arthritis education in the
      community. Reaching the community through the Accredited Social Health Activists
      (ASHAs) is the plan of action operational in India. Hence, the factors
      encountered by ASHAs while delivering arthritis education programs need to be
      studied. AIM: The aim of the study was to explore the experiences of ASHAs while
      delivering arthritis education program. MATERIALS AND METHODS: Qualitative
      exploratory design employing semi-structured interviews was adapted for the
      study. The interviews were conducted using focus groups of ASHAs from two
      geographically similar villages. Inductive analysis of focus group discussions
      was undertaken to determine themes, categories and codes. RESULTS: Three broad
      themes were identified from the interviews which influenced the performance of
      ASHAs. Categories identified show the influence of training, characteristics of
      ASHAs, geographical features, family characteristics and community attitude. Few
      problems reported were means of transport, time constraints, multiple tasks, type
      of incentive and frequency of on-field demonstrations. CONCLUSION: Providing
      motivation for altruistic services has always been a challenge to governing
      bodies. The issues identified in this study can be addressed prior to integrating
      ASHAs for rehabilitation services.

PMID- 28511496
TI  - Effect of Passive, Active and Combined Warm up on Lower Limb Muscle Performance
      and Dynamic Stability in Recreational Sports Players.
AB  - INTRODUCTION: Warm up is an activity that is done before a sports activity. The
      warm up can be done actively and passively. The preferred mode is active warm up
      in athletes. There are inconclusive effects of passive warm up compared with an
      active warm up on short term muscle performance. The cumulative effect of passive
      and active warm up on muscle performance and dynamic stability is not known. AIM:
      To find out the effects of passive, active and combined warm up on lower limb
      muscle performance and dynamic stability in recreational sports players.
      MATERIALS AND METHODS: A randomized crossover study was done on 19 recreational
      lower limb dominant sports players. Three different warm ups were included in the
      study passive, active and combined. Active warm up included series of activities
      like cycling, leg press, jump squats, squat jumps while passive warm up included
      application of moist heat for a period of 20 minutes on lower limb muscles.
      Combined warm up included both passive and active warm up. Six different
      sequences were made from these three warm ups. Subjects were screened and
      allotted into different groups based on the six warm up sequences after sequence
      randomization with 48 hours wash out period. After every warm up session Vertical
      Jump Test (VJT) and Star Excursion Balance Test (SEBT) was performed and results
      were recorded. Study duration was one year and six months. RESULTS: There was no
      difference noticed in both the outcome measures. Mean and SD values for passive,
      active and combined warm up are 47.62+/-9.64, 48.50+/-10.16 and 48.87+/-10.70
      respectively in Vertical Jump Test (VJT) and 85.43+/-8.61, 85.17+/-8.60 and
      85.17+/-8.38 respectively for SEBT. The p-value for mean difference between
      passive-active, active-combined, combined-passive are 0.67, 1.00, 0.51
      respectively, for VJT and 1.00, 1.00, 1.00 respectively for SEBT. CONCLUSION: All
      warm ups are equally effective in short term sports performance.

PMID- 28511497
TI  - Assessment of Oxidant-Antioxidant Status and Stress Factor in Recurrent Aphthous
      Stomatitis Patients: Case Control Study.
AB  - INTRODUCTION: Despite its vast occurrence, the aetiology of Recurrent Aphthous
      Stomatitis (RAS) still remains unknown and its aetiology is multifactorial. The
      factors believed to be associated with the aetiology of RAS, may disturb the
      equilibrium of oxidant-antioxidant status of the organism and may accelerate the
      formation of free radicals, resulting in Oxidative Stress (OS). Psychological
      stress is believed to act as a triggering factor or modifying factor for RAS.
      AIM: To find whether oxidant-antioxidant status and psychosocial stress play a
      role in the pathogenesis of RAS. MATERIALS AND METHODS: The study was conducted
      on 60 subjects over a period of one year (August 2014-August 2015) equally
      divided into two groups-patients with RAS and healthy controls. Psychosocial
      stress was analyzed by using Recent Life Changes Questionnaire (RLCQ). Saliva was
      analyzed to evaluate Superoxide Dismutase (SOD) and Glutathione Peroxidase
      (GSHPx) activities, Malondialdehyde (MDA) and Uric Acid (UA) levels in both the
      study and the control groups, using UV spectrophotometry. RESULTS: The mean value
      of salivary SOD and MDA was increased while the activity of GSHPx and UA
      decreased in the study group when compared to the controls; the difference being
      statistically significant (p<0.005). The mean RLCQ stress score was also found to
      be increased in the RAS group, which showed elevated levels of mental stresses
      when compared to physical stresses. No significant association was observed
      between SOD, MDA, GSHPx and UA with high levels of stress score (p>0.05). In the
      study group, no correlation was observed between the study variables and gender,
      the number of ulcer episodes in one year, the number of ulcers per episode or the
      duration of ulcers. CONCLUSION: This study shows that salivary antioxidant levels
      show a significant difference in response to OS in RAS patients. An increase in
      levels of psychosocial stress is seen associated with patients with RAS
      indicating its role as a modifying or triggering factor in the initiation of RAS.

PMID- 28511498
TI  - Antioxidant-Oxidant Index as a Biomarker in Oral Potentially Malignant Disorders
      and Oral Squamous Cell Carcinoma: A Biochemical Study.
AB  - INTRODUCTION: Oxidative stress has been implicated in tumourigenesis by affecting
      the actions of various protein kinases and transcription factors, and resulting
      in damage to DNA structure by the deamination of nucleotides and the generation
      of free radicals. Derangements in the antioxidant defence mechanism have been
      considered in the pathogenesis of oral cancer. AIM: To evaluate and compare the
      serum levels of nitric oxide and vitamin C in cases of Oral Potentially Malignant
      Disorders (OPMDs) and Oral Squamous Cell Carcinoma (OSCC) and healthy controls.
      MATERIALS AND METHODS: Serum from 20 patients with OSCC, 20 patients with OPMDs
      and 10 healthy subjects were analyzed for levels of nitric oxide and vitamin C
      using UV spectrophotometry. Antioxidant-Oxidant Index (AOI) was calculated by
      calculating the ratio between the levels of nitric oxide and vitamin C. RESULTS:
      The mean nitric oxide levels were elevated in OSCC group, as compared to OPMD and
      control group, whereas, mean serum vitamin C levels were reduced in OSCC group as
      compared to OPMDs and control group (statistically significant, p<0.05). There
      was significant increase in AOI from control group (0.023), OPMDs (0.167) and
      OSCC group (0.279) (p<0.05). CONCLUSION: Assessment of levels of antioxidant
      oxidant markers are useful tools in monitoring the progression of OPMDs to OSCC.
      AOI is an objective tool to assess the oxidative stress in these patients.

PMID- 28511499
TI  - Postoperative Pain and Flare-Ups: Comparison of Incidence Between Single and
      Multiple Visit Pulpectomy in Primary Molars.
AB  - INTRODUCTION: Endodontic treatment performed in either single- or multiple visit
      can be followed by numerous short- and long term complications. One of the short
      term complications include postoperative pain and flare-ups. The ability to
      predict its prevalence and forewarn the patient may go some way towards enabling
      coping strategies and help dentist in pain management treatment decisions. AIM:
      To compare the incidence and intensity of postoperative pain and flare-ups
      between single- and multiple visit pulpectomy in primary molars. Also, to
      correlate the preoperative status of the pulp to postoperative pain and flare
      ups. MATERIALS AND METHODS: Eighty primary molars indicated for pulpectomy were
      included in the study and divided into two groups. Tooth treated and preoperative
      status of the pulp vitality was recorded. All the conventional steps in
      pulpectomy were followed. Teeth in Group 1 (single visit pulpectomy) were
      obturated on the same visit. Teeth in Group 2 (multiple visit pulpectomy) were
      obturated in the subsequent appointment. The recording of postoperative pain,
      flare-ups, use of medication were done after 24 hours, seven days and one month.
      RESULTS: Four cases in both the groups reported postoperative pain (10%) at 24
      hour recall, p=0.74. One flare-up (2.5%) was recorded in each group p=0.67. None
      of the patients reported pain at seventh day and one month recall. Postoperative
      pain was recorded in five non-vital teeth (13.5%) and three vital teeth (6.9%).
      However, it was statistically not significant p=0.53. CONCLUSION: From the
      perspective of our study there was a low incidence of postoperative pain. The
      majority of patients in both groups reported no pain or only minimal pain within
      24 hours of treatment. There were no differences between single- and multi visit
      treatment protocols with respect to the incidence of postoperative pain. No
      significant correlation could be found between pulp vitality and the incidence of
      postoperative pain.

PMID- 28511500
TI  - Comparative Evaluation of the Efficacy of Probiotic, Herbal and Chlorhexidine
      Mouthwash on Gingival Health: A Randomized Clinical Trial.
AB  - INTRODUCTION: Due to inherent limitations of Chlorhexidine (CHX), search for an
      effective and potentially safe anti-plaque agent has led to emergence of
      alternative products. AIM: The present study evaluated the comparative efficacy
      of probiotic, herbal and CHX mouthwashes on gingival health of healthy
      individuals. MATERIALS AND METHODS: The present study was randomized parallel
      group controlled trial. A group of 45 healthy subjects in the age group of 18-21
      years received complete supragingival scaling at baseline and study variables
      viz., Oral Hygiene Index - Simplified (OHI-S), Plaque Index (PI) and Gingival
      Index (GI) were recorded. Subjects were then randomly divided into three groups
      (15 in each group) and were randomly intervened with three different mouthwashes
      i.e., HiOra mouthwash, CHX mouthwash and Probiotic mouthwash. Variables were
      again recorded on the seventh and 14th day after use of mouthwashes and data
      obtained was subjected to statistical analysis. RESULTS: There was no significant
      difference in the efficacy of CHX, HiOra regular and probiotic mouthwashes on
      plaque accumulation, gingival health and oral hygiene status. CONCLUSION: Herbal
      and probiotic mouthwashes can prove to be effective alternatives to CHX with
      minimal side effects.

PMID- 28511501
TI  - Gamma Glutamyl Transpeptidase, Smokeless Tobacco, Chronic Periodontitis:
      Exploring the Link.
AB  - INTRODUCTION: Oxidative Stress (OS) is implicated in the pathogenesis of many
      systemic and oral diseases such as periodontal disease. Smokeless tobacco extract
      produces apoptosis and causes an imbalance between reactive oxygen species and
      antioxidants, such as Gamma Glutamyl Transpeptidase (GGT). Epidemiological
      research implied serum GGT within its normal range to be an early sensitive
      enzyme related to OS. AIM: To assess how GGT fares as a biomarker in
      periodontitis subjects with or without the usage of smokeless tobacco and
      correlate it with clinical parameters. MATERIALS AND METHODS: Ninety subjects
      were divided into three groups of healthy, chronic periodontitis, and smokeless
      tobacco users with chronic periodontitis from the dental outpatient department of
      P.M. Nadagouda Memorial Dental College and Hospital. Serum samples of patients
      were collected after obtaining consent and analyzed for GGT. Statistical Analysis
      was performed using ANOVA, and Pearson's correlation coefficient. RESULTS: GGT
      levels were found to be significantly higher in chronic periodontitis patients
      compared to smokeless tobacco users with chronic periodontitis and healthy
      subjects. Conclusion: GGT may be used as a quick, easy and precise marker for
      measuring OS in patients with chronic periodontitis and smokeless tobacco users.

PMID- 28511502
TI  - Comparative Evaluation of Three Herbal Solutions on the Disinfection of
      Guttapercha Cones: An In vitro Study.
AB  - INTRODUCTION: Guttapercha (GP) cones are usually supplied in aseptic, sealed
      packages from the manufacturers, but once exposed to the dental office
      environment or even by handling; they can be contaminated by a number of
      microorganisms. Supplementary decontamination of GP cones is critical. As they
      cannot be sterilized by moist or dry heat, cold sterilization, using
      disinfectants should be used. AIM: The aim of the study was to evaluate rapid,
      reliable, convenient and effective method of disinfection of GP cones using
      readily available herbal solutions such as Aloevera Juice, Amla Juice and Pancha
      Tulsi. MATERIALS AND METHODS: Ninety GP cones were selected for the study. Based
      on the contaminants used, 80 GP cones were divided into two groups: Group A and
      Group B with 40 cones in each group and the remaining 10 cones which were
      uncontaminated served as negative control. The cones from Group A were
      contaminated with Staphylococcus aureus (S. aureus) and Group B were contaminated
      with Enterococcus faecalis (E. faecalis). The contaminated cones from both groups
      were subdivided into four groups with 10 cones in each group. Group I cones were
      disinfected with Aloevera Juice, Group II with Amla Juice and Group III with
      Pancha Tulsi. The fourth group consisted of GP cones without any disinfection
      which served as positive control. All the cones were then incubated in
      thioglycollate media for seven days. The thioglycollate media was subcultured and
      colony forming units were counted. The data were analyzed by one way ANOVA
      (analysis of variance) and Post-hoc Tukey test using SPSS 17.0 software. RESULTS:
      Mean colony forming units were compared in all the groups and there was a
      statistically significant difference present among the groups (p<0.01). Pancha
      Tulsi was found to be most effective disinfectant followed by Amla Juice.
      CONCLUSION: All the herbal solutions were found to be effective in the
      disinfection of GP points. However, Pancha Tulsi possesses superior antibacterial
      activity when compared with Aloevera Juice and Amla juice.

PMID- 28511503
TI  - Evaluation of Total and Lipid Bound Sialic Acid in Serum in Oral Leukoplakia.
AB  - INTRODUCTION: Oral cancer has become the most common cause of cancer related
      mortality which may be preceded by oral potentially malignant disorders. Altered
      glycosylation of glycoconjugates, such as sialic acid are one of the most
      important molecular changes accompanied during malignant transformation in
      precancerous lesions like Oral Leukoplakia (OL), and correlating them
      histopathologically with grades of epithelial dysplasia which will serve clinical
      significance. AIM: The aim of this study was to evaluate the significance of
      serum Total Sialic Acid (TSA) and serum Lipid Bound Sialic Acid (LSA) as a
      prognostic serum marker in Oral Leukoplakia. MATERIALS AND METHODS: Blood samples
      were collected from 30 patients diagnosed with OL and 30 healthy controls. Serum
      sialic acid (total and lipid bound) levels were measured using spectrophotometer.
      Tissue samples were histopathologically typed and were graded for epithelial
      dysplasia. Data were analysed using Independent t-test and Kruskal Wallis method.
      RESULTS: Serum levels of both total and lipid bound sialic acids were found to be
      increased in OL when compared to healthy controls. The mean TSA levels among
      those in the OL group (45.3+/-4.2) were significantly greater than healthy
      controls (29+/-2.2). On multiple comparison the highest mean TSA level was found
      in severe OL compared to moderate and mild OL (p<0.05). The mean levels of LSA
      were found to be statistically non-significant between the groups. CONCLUSION:
      The present study showed that the serum levels of both TSA and LSA were found to
      be increased in OL when compared to apparently healthy controls. We also found
      that with increasing grades of epithelial dysplasia TSA levels were found to be
      gradually increasing which was significant for this study serving as an early
      indicator for the detection of malignant transformation in OL.

PMID- 28511504
TI  - Prevalence of Distal Caries in Mandibular Second Molar Due to Impacted Third
      Molar.
AB  - INTRODUCTION: A tooth is said to be impacted if it does not reach the occlusal
      plane even after two-thirds root formation. The aetiology of impacted teeth is
      varied and multi-factorial. Significant problems associated with impacted teeth
      include trismus, infection, cervical caries of second molars. AIM: This study was
      aimed to assess the prevalence of distal caries in second molar teeth due to
      impacted third molars and to compare with similar studies conducted elsewhere.
      MATERIALS AND METHODS: Study included assessment of patients reporting between
      2009 to 2014 for dental care at College of Dentistry, King Khalid University,
      Abha, Kingdom of Saudi Arabia. This is a retrospective cross-sectional study
      which included a total of 6000 Orthopantomograms (OPGs). The data collected was
      decoded and entered into excel spread sheet. Descriptive analysis of the data was
      done and results were displayed as frequency table and graphs. RESULTS: A total
      of 979 patients had impacted third molars (16.31%). A total of 39% patient's with
      impacted third molars had distal cervical caries in second molar. Mesioangular
      impaction was the most prominent type. This was closely followed by horizontal
      impaction causing distal caries in second molars. Age group between 21-28 years
      and male gender had the higher prevalence of distal caries in second molar teeth
      due to impacted third molars. CONCLUSION: A total of 39% of the patients with
      impacted mandibular third molars had distal cervical caries in second molars.
      Mesioangular type, male gender, age group 21-28 years were the prominent factors
      associated with distal caries in second molar teeth due to impacted third molars.

PMID- 28511505
TI  - Effectiveness of Chewable Tooth Brush in Children-A Prospective Clinical Study.
AB  - INTRODUCTION: Dental plaque is one of the aetiological factors in causation of
      dental caries. Effective removal of plaque can reduce the incidence of caries.
      Various agents for removing plaque has been introduced, of which, chewable brush
      is a recent advance. There is limited evidence assessing the effectiveness of
      using chewable brush in children. AIM: The aim of this study was to evaluate the
      effectiveness of chewable brush in relation to efficiency in plaque removal and
      reduction in S.mutans counts in saliva. MATERIALS AND METHODS: Ten children of
      six-nine years with their first molars erupted were included in the study and the
      children were supervised for their normal brushing for 7 days. The baseline Oral
      Hygiene Index-Simplified (OHI-S), Plaque Index (PI) and Decay, Missing Filled
      Tooth Index (DMFT-I) were noted and the saliva sample was collected from the
      children. The sample was sent for microbiological examination of S.mutans count
      and the pH of the saliva was also determined. The children were advised to brush
      their teeth twice daily for seven days using chewable brush. On the seventh day,
      the indices were noted again and the saliva sample was collected and sent for
      microbiological examination. Statistical analysis was done using paired t-test to
      compare the pre and post-brushing index scores, S. mutans count and salivary pH.
      RESULTS: There was a significant reduction in the debris index (p<0.001), oral
      hygiene index (p<0.000), plaque index (p<0.001), pH of the saliva (p<0.037) and
      S. mutans level (p<0.006) before and after brushing with chewable brush. However,
      the calculus index remained unchanged (p=0.168). CONCLUSION: Chewable brush can
      be used as an effective alternative to manual brushing in children.

PMID- 28511506
TI  - An Assessment of Correlation between Dermatoglyphic Patterns and Sagittal
      Skeletal Discrepancies.
AB  - INTRODUCTION: Investigators over years have been fascinated by dermatoglyphic
      patterns which has led to the development of dermatoglyphics as a science with
      numerous applications in various fields other than being the best and most widely
      used method for personal identification. AIM: To assess the correlation between
      dermatoglyphic patterns and sagittal skeletal discrepancies. MATERIALS AND
      METHODS: A total of 180 patients, aged 18-40 years, were selected from those who
      attended the outpatient clinic of the Deparment of Orthodontics and Dentofacial
      Orthopedics, Mar Baselios Dental College, Kothamangalam, Kerala, India. The
      fingerprints of both hands were taken by ink and stamp method after proper hand
      washing. The patterns of arches, loops and whorls in fingerprints were assessed.
      The total ridge count was also evaluated. Data was also sent to the fingerprint
      experts for expert evaluation. The sagittal jaw relation was determined from the
      patient's lateral cephalogram. The collected data was then statistically analyzed
      using Chi-square tests, ANOVA and Post-hoc tests and a Multinomial regression
      prediction was also done. RESULTS: A significant association was observed between
      the dermatoglyphic pattern exhibited by eight fingers and the sagittal skeletal
      discrepancies (p<0.05). An increased distribution of whorl pattern was observed
      in the skeletal Class II with maxillary excess group and skeletal Class II with
      mandibular deficiency group while an increased distribution of loop pattern was
      seen in the skeletal Class III with mandibular excess group and skeletal Class
      III with maxillary deficiency group. Higher mean of total ridge count was also
      seen in the groups of skeletal Class II with maxillary excess and skeletal Class
      II with mandibular deficiency. Multinomial regression predicting skeletal pattern
      with respect to the fingerprint pattern showed that the left thumb impression
      fits the best model for predicting the skeletal pattern. CONCLUSION: There was a
      significant association between dermatoglyphic patterns and sagittal skeletal
      discrepancies. Dermatoglyphics could serve as a cost effective screening tool of
      these craniofacial problems.

PMID- 28511507
TI  - Evaluation of C-Reactive Protein and Fibrinogen in Patients with Chronic and
      Aggressive Periodontitis: A Clinico-Biochemical Study.
AB  - INTRODUCTION: Periodontal disease is characterised by chronic infection and
      inflammation in periodontal tissues leading to destruction of alveolar bone with
      subsequent tooth loss. Periodontal infections are the result of an interaction
      between tooth associated microbial biofilms and the host defences. Periodontal
      pathogens can affect local and systemic immune and inflammatory responses. AIM:
      The aim of the present study was to evaluate serum C-Reactive Protein (CRP),
      plasma fibrinogen and peripheral blood levels in healthy subjects, chronic and
      aggressive periodontitis patients. MATERIALS AND METHODS: A total of 55 subjects,
      27 males and 28 females were selected for the study. Blood samples were taken
      from healthy controls (n=20) and patients with chronic periodontitis (n=20) and
      aggressive periodontitis (n=15). The periodontal status of each patient was
      assessed by recording Oral Hygiene Index-Simplified (OHI-S), Bleeding Index (BI),
      Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL). The levels of
      serum CRP were measured using high sensitivity Enzyme Linked Immunosorbent Assay
      (ELISA) and levels of plasma fibrinogen were measured using Quantitative
      Immunoturbidimetric assay. Data description was done in the form of mean and
      standard deviation and analysis of data was done using one way ANOVA (Analysis of
      Variance) and Students t-test to test the statistical significance between
      groups. RESULTS: The levels of serum CRP and plasma fibrinogen was increased in
      patients with chronic and aggressive periodontitis when compared to healthy
      controls (p<0.001). A positive correlation was found to exist between levels of
      clinical parameters like OHI-S, BI, PPD and CAL when compared with CRP and
      fibrinogen as well as with the study groups. CONCLUSION: The finding of the
      present study suggests the role of serum as a diagnostic marker in inflammatory
      conditions and indicates that levels of CRP and fibrinogen may serve as important
      biomarkers for evaluating the association between periodontitis and
      cardiovascular diseases.

PMID- 28511509
TI  - Comparative Evaluation of Colour Stability and Surface Hardness of Methacrylate
      Based Flowable and Packable Composite -In vitro Study.
AB  - INTRODUCTION: With the advent of new technology in material sciences in recent
      years, the quality of composite resin restorations has improved; however,
      discolouration and wear of composite resin materials remains to be a major
      problem in long-term clinical studies. AIM: The aim of the present study was to
      compare the colour stability and surface hardness of methacrylate based flowable
      nano composite with methacrylate based packable nano composite. MATERIALS AND
      METHODS: The difference in colour stability and microhardness of the three
      composites: G aenial Universal Flo (GC India), Filtek Z350XT (3MESPE) and Tetric
      N Ceram (Ivoclar Vivadent) were evaluated. Forty eight disc shaped specimens were
      made out of three different resin composite materials which were subdivided into
      two groups of Colour Stability (CS) and Vicker's Hardness (VH). For colour
      stability, specimens were immersed in staining solution consisting instant coffee
      for 72 hours, and then specimens were rinsed thoroughly under tap water and
      subjected to 10 strokes of brushing with a soft-grade toothbrush. The colour
      measurements were obtained using spectrophotometer and the process was repeated
      every 72 hours for three weeks. VH was evaluated using microhardness tester
      (Zwick/Roell Vicker's Microhardness Tester). Vicker's Hardness Numbers (VHN) were
      determined from indentations made under 10 N load for 15 seconds by the
      arithmetic mean of three indentation values randomly performed. One-way ANOVA and
      Tukey's post-hoc analysis were applied. RESULTS: Statistically significant
      difference was found in comparison of colour stability at different time interval
      in study groups (p<0.001). Filtek Z350XT group showed least discolouration
      followed by Tetric N Ceram group and highest colour change in G aenial Universal
      Flo group after immersion for 21 days. Mean microhardness value of Filtek Z350XT
      (101.62) group was found to be significantly different from Tetric N Ceram group
      (63.74) (p<0.001*) and G aenial Universal Flo group (56.75) (p<0.001*).
      CONCLUSION: Greatest CS and VH was seen in Filtek Z350XT followed by Tetric N
      Ceram and least values were seen in G aenial Universal Flo.

PMID- 28511510
TI  - Patterns of Partial Edentulism and its Relation to Khat Chewing in Jazan
      Population - A Survey Study.
AB  - INTRODUCTION: Partial edentulism is a prime indicator of overall oral health in a
      given country. Khat chewing habit in the south region of Saudi Arabia is widely
      practiced by a majority of the population. AIM: To determine the frequency of
      Kennedy's classes in each arch among different age groups, gender and to find out
      the relationship between khat chewing and the pattern of partial edentulism.
      MATERIALS AND METHODS: The data was collected from 780 subjects reporting to the
      College of Dentistry, Jazan University, who required removable partial dentures.
      Clinical intra-oral and radiographic examinations were done. The study subjects
      were divided into five age groups, 20-29, 30-39, 40-49, 50-59 and >= 60 years
      respectively. Khat chewing hours/day and type of Kennedy's classes were recorded.
      The data were entered into a Statistical Package for Social Sciences program and
      analysed accordingly using Fisher-Exact test. RESULTS: Class III was the highest
      in all middle age groups followed by Class I. Class III was the highest in males,
      while in females, Class I was the highest in both arches. Class IV was the lowest
      in all age groups, both arches, and genders. Among khat chewers Class III was the
      highest followed by class I in both arches. Class IV was the highest in >12 hours
      duration in maxilla but in the mandible, Class I and II were the highest in 1-6
      hours duration. The obtained p-values were statistically significant (p<0.001) in
      all tested variables and age groups. CONCLUSION: Kennedy's Class III was the
      highest followed by Class I, while Kennedy's Class IV was the lowest in all age
      groups and both arches regardless of khat chewing durations. In males Class III,
      was the highest, while in females Class I was the highest in both arches.

PMID- 28511508
TI  - A Randomized Placebo- Controlled Double Blind Clinical Trial of Quercetin in the
      Prevention and Treatment of Chemotherapy-Induced Oral Mucositis.
AB  - INTRODUCTION: Oral Mucositis (OM) is a serious complication of chemotherapy that
      results in painful debilitating inflammation that sometimes ends in interruption
      of treatment. AIM: The study evaluated the effect of quercetin (a natural
      flavonoid) on preventing and treating chemotherapy induced OM in patients with
      blood malignancies. Materials and Methods: This double-blind, placebo controlled
      randomized trial was carried out on 20 adult patients who underwent high dose
      chemotherapy for blood malignancies. Patients were divided into two groups (10
      patients in the intervention group and 10 patients in the control group).
      Patients in the intervention group were administered 250 mg quercetin capsules
      twice daily for four weeks. RESULTS: Nine out of 20 patients developed OM (three
      in the intervention group and six in the control group). The incidence of OM was
      lower in the intervention group although it was not statistically significant
      (p=0.189). The mean severity of OM was higher in the intervention group (2.6 vs
      2). Healing time, age, gender, type of malignancy, drug type and duration of OM
      were not different in two groups. CONCLUSION: The incidence of mucositis was
      lower in the quercetin group, but mucositis was more severe in the intervention
      group, which may be due to lower oral health status in the intervention group.

PMID- 28511511
TI  - Health-Related Quality of Life of Persons after Rhinoplasty: A Longitudinal Study
      among Iranian Population.
AB  - INTRODUCTION: Despite the growing number of cosmetic rhinoplasty surgeries in
      Iran in recent years, there is little information about the effects of this
      procedure on the subjects' Quality of Life (QoL). This study examined the QoL
      after rhinoplasty in subjects without nasal obstruction, who wanted the surgery
      for aesthetic reasons, three and six months postoperatively. AIM: The aim of this
      study was to assess the changes of QoL in clients who take rhinoplasty. MATERIALS
      AND METHODS: This was a prospective study conducted in Tehran, Iran. Using
      convenience sampling, 150 subjects who had undergone cosmetic rhinoplasty from
      June 2013 to June 2014 were invited to participate in the study. Patients' QoL
      was measured one week before and three and six months after rhinoplasty, using
      the Iranian version of the 36-item Short Form (SF-36) questionnaire. Descriptive
      statistics, Pearson correlation coefficient, one-way ANOVA, paired t-test, and
      independent sample t-test were used for data analysis. RESULTS: Most of the
      participants were women (64%), and the mean age was 26.8+/-5.4 years (range: 18
      41 years). The mean QoL scores before and three and six months after rhinoplasty
      were 67.26+/-26.01, 68.00+/-15.7 and 83.65+/-9.6, respectively. None of the
      measured demographic characteristics showed any correlation or relationship with
      the participants' QoL before and after the procedure (p>0.05). CONCLUSION: QoL
      can be considered as a quality indicator of health care systems. This study shows
      that the persons' QoL improved six months after cosmetic rhinoplasty.

PMID- 28511513
TI  - Sexual Dimorphism of Maxillary Sinus: A Morphometric Analysis using Cone Beam
      Computed Tomography.
AB  - INTRODUCTION: Age and sex determination in forensic sciences are primary
      components of any skeletal analysis. As most bones used for sex determination are
      recovered in incomplete state, it is often necessary to use bones that are
      recovered intact e.g., the maxillary sinus. Cone Beam Computed Tomography (CBCT)
      can provide precise information about complex anatomical structures, as it is
      characterized by rapid volumetric image acquisition with high resolution. AIM:
      The present study was designed to evaluate the size and volume of Maxillary Sinus
      (MS) in determining gender by CBCT. MATERIALS AND METHODS: Bilateral maxillary
      sinus images (left and right) were acquired for 100 patients (50 females and 50
      males) and different parameters (width, length, height, area, perimeter and
      volume) were measured and evaluated. Mean and standard deviation of both
      maxillary sinuses measurements were calculated and compared. The data was
      subjected to discriminative statistical analysis and analysed using unpaired t
      test. RESULTS: Comparison between male and female groups showed statistically
      insignificant differences on both the right and left sides with respect to the
      maxillary sinus length, height, area, volume and perimeter. However, the female
      group showed statistically significant higher values for left side MS width
      (p=0.041) and left side MS width can be used to determine gender with an overall
      accuracy of 60%. The final result of discriminative analysis shows that the
      ability of the maxillary sinus to identify gender was 68% in males and 74% in
      females with an overall accuracy of 71%. CONCLUSION: Maxillary sinus width can be
      used as an aid in forensic anthropology for gender determination.

PMID- 28511512
TI  - Evaluation of Correlation between Salivary Calcium, Alkaline Phosphatase and
      Osteoporosis- A Prospective, Comparative and Observational Study.
AB  - INTRODUCTION: Fixed and/or removable prosthodontics caters to the restorative
      needs of the largest count of geriatric patients whose rehabilitative procedures
      depend on the quality and quantity of available bone. The common diagnostic
      parameters for quantifying bone may involve an invasive blood examination, an
      expensive bone densitometry procedure or a urine analysis. Sialometry involving
      the basic biochemistry of saliva analysis may be proposed as an alternative to
      the conventional investigative protocol and its usefulness may be attributed
      owing to its non invasive and simpler procedure. AIM: The aim of this study was
      to compare the salivary calcium and alkaline phosphatase among osteoporotic,
      osteopenic and normal edentulous subjects. MATERIALS AND METHODS: A prospective,
      comparative and observational study was carried out on 80 selected edentulous
      subjects (40 males and 40 females) aged 55-75 years (30 osteoporotic, 30
      osteopenic and 20 control). A sample of saliva was taken for the study. Salivary
      calcium was measured by Arsenazo reaction; and alkaline phosphatase by the
      International Federation of Clinical Chemistry (IFCC) method. Statistical
      analysis was done by unpaired t-test. A comparison was made in the levels of
      salivary calcium and alkaline phosphatase with that of osteoporosis and
      osteopenia. RESULTS: The mean salivary calcium and alkaline phosphatase levels
      were found to be significantly higher in the osteoporotic and osteopenic
      edentulous subjects as compared to the control group. CONCLUSION: Salivary
      calcium and alkaline phosphatase are increased significantly in case of
      osteoporosis and osteopenia. Hence, screening of salivary samples of patients may
      be an effective indicator for the detection of underlying disorders of bone
      metabolism.

PMID- 28511514
TI  - Evaluation of Relative Position of Mandibular Foramen in Children as a Reference
      for Inferior Alveolar Nerve Block using Orthopantamograph.
AB  - INTRODUCTION: The Mandibular Foramen (MF) is a landmark for administering local
      anaesthetic solution for Inferior Alveolar Nerve Block (IANB). The position of MF
      shows considerable variation among different ethnicity, ages and on either sides
      even within the same individual. Failure to achieve IANB leading to repeated
      injection of the local anaesthetic solution will not only pose a behaviour
      problem in children but can also lead to systemic toxic level of anaesthetic
      solution being administered. AIM: To determine the relative position of the
      mandibular foramen in 7 to 12-year-old children in relation to the mandibular
      occlusal plane and the deepest point on coronoid notch. MATERIALS AND METHODS:
      Ninety orthopantamograph of 7 to 12-year-old children were selected from the
      database and were divided into three groups: Group 1 (G1): seven to eight-year
      old, Group 2 (G2): 9 to 10-year-old and Group 3 (G3): 11 to 12-year-old. The
      radiographs were traced on acetate paper, anatomical landmarks were marked and
      linear measurements were noted from the Mandibular Lingula (ML) to the occlusal
      plane, and to the deepest point on coronoid notch. The data obtained was
      tabulated and subjected to statistical analysis. One way ANOVA test followed by
      Bonferroni post hoc analysis and Student's paired t-test were used. RESULTS:
      Mandibular foramen is approximately, 2-3 mm above the occlusal plane and 11.6
      13.0 mm from deepest point of coronoid notch for seven to eight-year-old
      children, 3-4 mm above the occlusal plane and 13.0-13.9 mm from deepest point of
      coronoid notch for 9-10 year age group and 5.5-6.5 mm above the occlusal plane
      and 11.9-12.2 mm from deepest point of coronoid notch for children of the ages 11
      12 years. The linear distance from the deepest point of coronoid notch to the
      mandibular lingula showed statistical significance in G2 vs G3 on right side G1
      vs G2 and G2 vs G3 on the left side. The variance of this distance for either
      side showed statistical significance for G1 and G2. CONCLUSION: The distance from
      the mandibular lingula to the occlusal plane showed gradual increase in all the
      three groups, which was statistically significant. The position of the mandibular
      foramen is not bilaterally symmetrically for any of the considered age groups.

PMID- 28511515
TI  - Comparative Evaluation of Antibacterial and Adhesive Properties of Chitosan
      Modified Glass Ionomer Cement and Conventional Glass Ionomer Cement: an In vitro
      Study.
AB  - INTRODUCTION: Recent studies have reported the incorporation of modifiers with
      conventional Glass Ionomer Cement (GIC) to enhance its antibacterial effect. One
      such modification being the addition of Chitosan (CH). However, these modifiers
      might affect the physical properties of the restorations. AIM: The aim of the
      present study was to investigate the effect of modifying the liquid phase of
      conventional GIC with 10% v/v CH on the antibacterial properties and adhesion to
      enamel in comparison to conventional GIC. MATERIALS AND METHODS: The liquid of
      commercially available restorative GIC (Fuji IX, GC Industrial Corporation,
      Japan) was modified with 10% v/v CH solution (Everest Biotech, Bengaluru). GIC
      powders were mixed with the unmodified and the CH-modified liquids at the desired
      powder/liquid ratio. Fourier Transform Infrared Spectroscopy (FTIR) was used to
      determine the setting reaction between the conventional and CH modified GIC
      liquid with GIC powder. For evaluation of the antibacterial properties, biofilms
      of Streptococcus mutans (S. mutans) were formed on the GIC discs and
      characterized by Scanning Electron Microscope (SEM). For the characterization of
      the adhesive properties, the unmodified and CH-modified GICs were bonded to the
      enamel surface and the microshear bond strength (MUSBs) was evaluated. Student's
      paired t-test was used to compare the micro-shear bond strength between CH
      modified GIC and unmodified GIC. RESULTS: Modification with 10% v/v CH solution
      improved the antibacterial properties of GIC against S. mutans in terms of
      resistance to biofilm formation which was assessed using SEM. Microshear bond
      strength of CH modified GIC was 85.40 MPa compared to 46.94 MPa of conventional
      GIC. This difference was found to be statistically significant. CONCLUSION:
      Modifying the liquid phase of a conventional GIC with 10% v/v CH significantly
      improves the antibacterial property of GIC as well as its adhesion to enamel.

PMID- 28511516
TI  - To Evaluate and Compare Periodontal Disease and Smoking as a Parallel Risk Factor
      for Systemic Health by Gauging the Serum C-Reactive Protein Levels.
AB  - INTRODUCTION: Physiologic and metabolic changes that occur immediately after a
      damage or disease are known as Acute Phase Reaction (APR). Acute Phase Proteins
      (APP) are blood proteins secreted by hepatocytes during APR C-Reactive Protein
      (CRP) being the important one. AIM: Present study was designed to estimate and
      compare the levels of the serum CRP in current smokers, former smokers and non
      smokers, with and without periodontitis. MATERIALS AND METHODS: An experimental
      study was planned on 165 subjects who were divided into four groups. Group 1-
      nonsmokers with periodontitis. Group 2- smokers without periodontitis. Group 3-
      smokers with periodontitis. Group 4- former smokers without periodontitis.
      Healthy controls were not included in the study as the normal range of CRP in
      health is already established. Periodontal examination was done and serum CRP was
      measured. After getting the acceptance to be a part of the study, written
      informed consent was taken from each participant. Data analysis was done by ANOVA
      and post-hoc tests. RESULTS: Highest level of CRP was found in smokers with
      periodontitis followed by non-smokers with periodontitis and smokers without
      periodontitis. Former smokers had minimum CRP compared to the other groups (p
      value=0.03). CONCLUSION: Periodontitis alone and in combination with smoking
      increases the systemic inflammatory burden and associated cardiovascular risk.
      This fact should be communicated thoroughly to the general population, general
      dentist, physicians and cardiovascular specialist to enhance early screening and
      multidisciplinary treatment.

PMID- 28511517
TI  - Holistic Healing Through Herbs: Effectiveness of Aloe Vera on Post Extraction
      Socket Healing.
AB  - INTRODUCTION: Advances in the field of alternative medicine has encouraged the
      use of various natural products for multiple uses in the field of dentistry for
      treatment of various oral diseases. A natural herbal product is Aloe vera, which
      has number of benefits with no reported side effects and gaining considerable
      importance in clinical research. AIM: The aim of this cross-sectional randomized
      interventional study was to evaluate the effectiveness of Aloe vera in the
      healing of post extraction sockets. MATERIALS AND METHODS: A sample size of 40
      patients undergoing atraumatic extraction was divided into two groups. Group A
      patients were prescribed only analgesics and followed for seven consecutive days
      and socket healing assessment was done. Group B-Patients were given Aloe vera
      soaked gel foams, followed up to the third and seventh day by two observers and
      the socket healing was assessed using the standardized index by Landry, Turnbull
      and Howley. In addition to healing the common complaint associated with
      extraction wound, the pain was assessed using numerical rating scale. Data
      obtained was statistically analysed using Mann-whitney U test, Wilcoxon Signed
      ranks test and Spearman's rank correlation method. RESULTS: Control group on the
      third and the seventh day showed healing of 60% and 70% respectively and the Aloe
      vera group showed a better result having a healing potential of 70% on the third
      day and 90% on the seventh day which was statistically significant with a (p
      value<0.001). Aloe vera group showed a significant decrease in pain after two
      hours on the day of extraction followed by second, third and seventh day which
      was statistically significant (p-value<0.001) and better than the control group.
      CONCLUSION: Aloe vera has been proved to have a unique property that is
      implicated in better healing than other group without any side effects. Aloe vera
      is economical, effective, powerful nutritional supplement and antioxidant that
      protects and promotes wound healing.

PMID- 28511518
TI  - Fat Free Pleomorphic Lipoma of Oral Cavity: A Rare Entity.
AB  - Pleomorphic lipoma is a rare, benign, soft tissue neoplasm that
      characteristically occurs as a subcutaneous mass in the posterior neck or upper
      back and rarely in the tonsillar fossa and oral cavity. Histologically,
      pleomorphic lipoma contains varying amounts of mature fat, areas of spindle and
      pleomorphic cells, floret giant cells and thick rope - like collagen in a myxoid
      stroma. Pleomorphic lipoma with scanty fatty elements is called the fat free
      variant of pleomorphic lipoma. The combination of meagre amount of fat and
      presence of pleomorphic elements gives a pseudosarcomatous picture under the
      microscope leading to misdiagnosis and over treatment. Here, we report a case of
      fat free pleomorphic lipoma, first of its kind in the oral cavity and discuss the
      diagnostic features and differential diagnosis.

PMID- 28511519
TI  - A Giant Cutaneous Horn Projecting from Verrucous Carcinoma of Buccal Mucosa: A
      Rare Case Report.
AB  - Cutaneous horn is conical shape of compact keratin that resembles a miniature
      animal horn. Though morphologically similar to horns in animals they are
      histologically very different from them. It is a circumscribed, conical,
      hyperkeratotic dense protrusion with epithelial cornification above the skin
      surface in response to a wide range of underlying benign and malignant
      pathological changes. Though benign, a cutaneous horn holds the potential to be
      premalignant or malignant. In India till now six cases has been reported with
      cutaneous horn at various unusual sites. We report a unique case of 52-year-old
      woman with a giant cutaneous horn at left oral commissure with underlying
      verrucous carcinoma of left buccal mucosa which is a very rare location for such
      lesion. Considering its malignant potential, adequate therapy requires wide
      excision with a tumour-free margin of at least 1 cm, particularly in the facial
      region where the incidence of malignancy is higher.

PMID- 28511520
TI  - Effect of Trauma to Primary Tooth on Permanent Maxillary Incisors: A Clinical
      Case Report.
AB  - Trauma to primary tooth leads to abnormal variations in crown and root canals of
      permanent teeth that presents a challenge in diagnosis and clinical management to
      the practitioner. This article presents a detailed case report of the endodontic
      treatment of a three canalled maxillary central incisor and maxillary lateral
      incisor having single canal with open apex linked with periodontal defect. Root
      canals were prepared with hand files and canals were irrigated with 2.5% sodium
      hypochlorite solution. Calcium hydroxide was placed as an intracanal medicament.
      As the expected healing did not occur even after one month of calcium hydroxide
      therapy, so periapical endodontic surgery was performed using Platelet Rich
      Plasma (PRP). Satisfactory clinical and radiographic results were obtained at 12
      months. Detailed knowledge of the anatomical variations in the root canal and
      awareness of their configuration is essential for the success of such cases.

PMID- 28511521
TI  - Cu-sil Denture- A Space Maintainer for Function- In Paediatric Patients.
AB  - The purpose of this report is to introduce Cu-sil like denture as a functional
      space maintainer. Here, we report two paediatric cases treated with Cu-sil like
      denture with multiple edentulous spaces and partially erupted/compromised
      permanent teeth. Cu-sil like denture not only serves as removable partial
      functional space maintainer, but also restores the vertical dimension of
      occlusion, mastication and aesthetics in children. Cu-sil like denture is used in
      elderly patients who are not willing for extraction of remaining few healthy
      teeth in the oral cavity. This concept utilizes the remaining natural teeth in
      the arch, accommodates them within the denture through perforations made in the
      denture base. The gap between the denture base and the tooth is sealed using a
      resilient liner. Such denture is used for the paediatric age group in this report
      for functional rehabilitation temporarily. The report describes the pros and cons
      of the Cu-sil like denture use in children with technique of preparation along
      with review of literature.

PMID- 28511522
TI  - Iris Positioning Using a Grid Attached to a Spring Bow for a Custom Ocular
      Prosthesis.
AB  - Eyes are among the first features of the face to be noticed. Loss of an eye due
      to congenital, traumatic or pathologic aetiologies causes disfigurement and loss
      of sensory feedback. It leaves a psychological impact on the patient, thus
      prosthesis should be provided at the earliest to raise the spirits of the
      afflicted. Iris positioning is one of the important steps in fabricating
      customized ocular prosthesis. In facial asymmetry cases, comparison of both
      irises together can be a major disadvantage. This case report illustrates the use
      of a unique customized frame spring bow assembly to position the iris disk using
      the established parallelism between inter pupillary line to the horizontal plane.

PMID- 28511523
TI  - Achondroplasia with Polydactyly: A Case Report.
AB  - An eight-year-old girl child reported to the Department of Oral Medicine and
      Radiology with the chief complaint of unerupted permanent teeth for past two
      years. The child presented features like disproportionately short stature,
      rhizomelic shortening of arms and legs, long face, frontal bossing and saddle
      nose. Based on the findings of chest and spine radiographs and ultrasound the
      case was diagnosed as a rare bone disorder "Achondroplasia". This case also
      presents a unique feature of polydactyly. Polydactyly is a manifestation in
      clinical medicine because it can serve as an indicator for a plethora of
      congenital anamolies. This case gained dental interest because of its
      characteristic craniofacial features. This article highlights the peculiar
      manifestations of this anamoly.

PMID- 28511525
TI  - Rehabilitation of a Patient with Facial and Palatal Defect - A Case Report.
AB  - Defects involving the face and maxilla present a challenge to the prosthodontists
      as these have a direct effect on aesthetics, function as well as the psychology
      of the patient. An array of problems awaits the clinician from restoring the
      previous contour of the oral cavity, facial form, etc. to the mental state of the
      patients. This article deals with the rehabilitation of a hemimaxillectomy
      patient with a facial defect, using an interim hollow bulb obturator and a
      silicone facial prosthesis, which helped to improve the general well being of the
      patient. Rehabilitative procedures provide patients considerable care so that
      they can continue their life with confidence.

PMID- 28511524
TI  - Basaloid Squamous Cell Carcinoma of Tongue: A Report with Emphasis on
      Immunohistochemistry.
AB  - Basaloid Squamous Cell Carcinoma (BSCC) is a rare entity with its
      histopathological distinction from conventional squamous cell carcinoma. It is
      frequently considered a high-grade carcinoma with poor prognosis because of
      higher rate of distant metastases. Here by, we are reporting a case of 39-year
      old male with an ulcer on the left lateral border of the tongue since a month.
      Histopathological examination of incisional biopsy revealed basaloid tumour cell
      islands accompanied by component of well differentiated squamous cell carcinoma.
      To reconfirm this incidental finding immunohistochemistry was carried out for
      Proliferative Cell Nuclear Antigen (PCNA) and pancytokeratin (AE1/AE3) which was
      positive to conclude diagnosis of BSCC. Further p16 staining was done to rule out
      Human Papilloma Virus (HPV) infection.

PMID- 28511526
TI  - Angiolymphoid Hyperplasia with Eosinophilia Involving the Occipital Artery: Case
      Report and Review of Literature.
AB  - Angiolymphoid Hyperplasia with Eosinophilia (ALHE) is an atypical vascular tumour
      occurring primarily in the head and neck area, which must be distinguished from
      Kimura's disease. The lesions can appear as single or multiple grouped
      intradermal papules or subcutaneous nodules. We report a rare case of ALHE in a
      57-year-old female with a large lesion of three nodules involving the right
      occipital artery which had a long term evolution and we treated it by surgical
      excision. The definitive histopathological diagnosis was ALHE. Our case report is
      accompanied by a discussion of clinical, radiological and histological features.
      Surgical excision with free margins is the treatment of choice but, even though
      ALHE is considered a benign condition, recurrence is common.

PMID- 28511527
TI  - Temporary Blindness after Inferior Alveolar Nerve Block.
AB  - Inferior Alveolar Nerve Block (IANB) anaesthesia is one of the common procedures
      in dental clinic. This procedure is safe, but complications may still occur.
      Ocular complications such as diplopia, loss of vision, or ophthalmoplegia are
      extremely rare. This case report explains an event where due to individual
      anatomic variation of the sympathetic vasoconstrictor nerve and maxillary and
      middle meningeal arteries, intravascular administration of anaesthetic agent
      caused unusual ocular signs and symptoms such as temporary blindness.

PMID- 28511528
TI  - Immediate Placement of Zirconia Implants in Teeth with Periapical Lesions: A Case
      Report.
AB  - This case report records the replacement of two failed endodontically treated
      mandibular molars with one piece zirconia implants in a patient with metal
      hypersensitivity. The two molars were atraumatically extracted and curetted to
      remove any remnants of a periapical granuloma. Immediate implant placement with
      primary stability was achieved using one piece WhiteSky(r) Bredent zirconia
      implants which were restored after four months with a zirconia crown. One year
      follow up revealed successful osseointegration with optimal form and function.

PMID- 28511529
TI  - Orthodontic Therapy for Paediatric Cancer Survivors: A Review.
AB  - The paper aims at reviewing the possibilities of orthodontic therapy for
      paediatric cancer survivors. It is important to understand the fundamental
      disease, it's treatment protocols, effects on growing skeleton, dental
      development, oral cavity and oral mucosa, dental caries, bone, orthodontic tooth
      movement.

PMID- 28511531
TI  - Occurrence of Cusp of Carabelli in Primary Second Molar Series of three Cases.
AB  - Morphological variations are seen in both primary and permanent dentitions. Cusp
      of Carabelli is also one of them. It is suggested that it is due to over activity
      of dental lamina but definitive aetiology is unknown. It is a type of accessory
      cusp, occurs more often in permanent maxillary first molars, whereas, its
      occurrence in primary tooth is rare. The present case series discusses the
      presence of cusp of Carabelli in primary maxillary second molars in three
      different cases. This case series will help clinicians to identify, diagnose and
      take proper preventive care and also adds to the incidence in literature.

PMID- 28511530
TI  - Herbs in Oral Mucositis.
AB  - Oral mucositis is an inflammatory mucosal destruction as a result of chemotherapy
      and/or radiation therapy, which in severe cases can impair patients' quality of
      life. Moreover, mucosal infection and/or systemic involvement due to compromised
      immunity leads to delay or discontinuation of the treatment. Many strategies and
      agents have been suggested for the management of this condition. Because of their
      lower side effects compared to chemical drugs, general interest in evaluating
      therapeutic effects of herbs has been increased intensively. Herbal plants apply
      their effect through different mechanisms of action: antioxidant, analgesic, anti
      inflammatory, antifungal, antiseptic, and anticarcinogenic activity. Recently,
      various natural agents in plants have been noticed in mucositis, which may
      improve the symptoms through different interventions. The purpose of this review
      is to focus on the preventive or therapeutic use of herbal medicine to alleviate
      oral mucositis.

PMID- 28511532
TI  - Kedo-S Paediatric Rotary Files for Root Canal Preparation in Primary Teeth - Case
      Report.
AB  - Nickel-Titanium (Ni-Ti) instrument are widely used for root canal preparation in
      permanent tooth compared to primary teeth. Hand instrumentation technique remains
      the conventional method for root canal preparation in primary teeth. The time
      taken for root canal preparation with the conventional method is more resulting
      in patients and clinicians fatigue. Recently Ni-Ti rotary files designed for
      permanent tooth has been used for root canal preparation in primary teeth. Using
      rotary instruments for primary tooth pulpectomies resulted in better and
      predictable root canal filling. This article presents case reports of pulpectomy
      treatment performed using Kedo-S an exclusive paediatric Ni-Ti rotary files. The
      advantages and disadvantages in use of Ni-Ti rotary files in primary teeth are
      discussed in this article.

PMID- 28511533
TI  - Composition, Morphology, and Topography of Galvanic Coatings Fe-Co-W and Fe-Co
      Mo.
AB  - Ternary coatings Fe-Co-W with an iron content of 40-55 at.%, cobalt 39-44 at.%,
      and tungsten 4-12 at.% and Fe-Co-Mo with an iron content of 40-55 at.%, cobalt 39
      44 at.%, and tungsten 4-12 at.% were obtained by galvanostatic and pulse
      electrolysis on the mild steel substrate from iron(III) citrate-based
      electrolyte. The influence of electrolysis mode and parameters on composition of
      deposited alloys was studied. The competing reduction of iron and tungsten in Fe
      Co-W coatings as well as the competitive deposition of iron and cobalt in Fe-Co
      Mo coatings at various current densities were defined. Simultaneously, the alloy
      enrichment with molybdenum is more marked at a pulse mode. Atomic force
      microscope analysis of the Fe-Co-W alloy coating morphology and surface
      topography indicates their globular structure with spherical grains in the range
      of 2.5-3.5 MUm. The surface of Fe-Co-Mo is characterized by parts of a globular
      structure with an average conglomerate size of 0.3-0.5 MUm and singly located
      cone-shaped hills with a base diameter of 3 MUm. Sites with a developed surface
      were detected within the same scan area which topography is identical to the
      crystal lattice of cobalt with the crystalline conglomerate sizes in the range of
      0.2-1.75 MUm.

PMID- 28511534
TI  - Ferroelectric domain states of a tetragonal BiFeO3 thin film investigated by
      second harmonic generation microscopy.
AB  - We investigate the ferroelectric state of a tetragonal BiFeO3 thin film grown on
      a LaAlO3 (001) substrate using an optical second harmonic generation (SHG)
      microscope. Whereas the ferroelectric state of this material hosts nanometer
      sized domains which again form micrometer-sized domains of four different
      configurations, we could figure out the characteristic features of each domain
      from the SHG mapping with various sizes of the probe beam, i.e., from 0.7 to 3.9
      MUm in its diameter. In particular, we demonstrate that a single micrometer-sized
      domain contributes to the SHG as a coherent summation of the constituent
      nanometer-sized domains, and multi-micrometer-sized domains contribute to the SHG
      as an incoherent summation of each micro-domain.

PMID- 28511535
TI  - Surface Morphology Evolution Mechanisms of InGaN/GaN Multiple Quantum Wells with
      Mixture N2/H2-Grown GaN Barrier.
AB  - Surface morphology evolution mechanisms of InGaN/GaN multiple quantum wells
      (MQWs) during GaN barrier growth with different hydrogen (H2) percentages have
      been systematically studied. Ga surface-diffusion rate, stress relaxation, and H2
      etching effect are found to be the main affecting factors of the surface
      evolution. As the percentage of H2 increases from 0 to 6.25%, Ga surface
      diffusion rate and the etch effect are gradually enhanced, which is beneficial to
      obtaining a smooth surface with low pits density. As the H2 proportion further
      increases, stress relaxation and H2 over- etching effect begin to be the dominant
      factors, which degrade surface quality. Furthermore, the effects of surface
      evolution on the interface and optical properties of InGaN/GaN MQWs are also
      profoundly discussed. The comprehensive study on the surface evolution mechanisms
      herein provides both technical and theoretical support for the fabrication of
      high-quality InGaN/GaN heterostructures.

PMID- 28511536
TI  - Biomimetic Silica Nanocapsules for Tunable Sustained Release and Cargo
      Protection.
AB  - Silica nanocapsules have attracted tremendous interest for encapsulation,
      protection, and controlled release of various cargoes due to their unique
      hierarchical core-shell structure. However, it remains challenging to synthesize
      silica nanocapsules having high cargo-loading capacity and cargo-protection
      capability without compromising process simplicity and biocompatibility
      properties. Here, we synthesized oil-core silica-shell nanocapsules under
      environmentally friendly conditions by a novel emulsion and biomimetic dual
      templating approach using a dual-functional protein, in lieu of petrochemical
      surfactants, thus avoiding the necessities for the removal of toxic components. A
      light- and pH-sensitive compound can be facilely encapsulated in the silica
      nanocapsules with the encapsulation efficiency of nearly 100%. Release of the
      encapsulated active from the nanocapsules was not shown an indication of
      undesired burst release. Instead, the release can be tuned by controlling the
      silica-shell thicknesses (i.e., 40 and 77 nm from which the cargo released at
      42.0 and 31.3% of the initial amount after 32 days, respectively). The release
      kinetics were fitted well to the Higuchi model, enabling the possibility of the
      prediction of release kinetics as a function of shell thickness, thus achieving
      design-for-purpose silica nanocapsules. Furthermore, the nanocapsules showed
      excellent alkaline- and sunlight-shielding protective efficacies, which resulted
      in significantly prolonged half-life of the sensitive cargo. Our biomimetic
      silica nanocapsules provide a nanocarrier platform for applications that demand
      process scalability, sustainability, and biocompatibility coupled with unique
      cargo-protection and controlled-release properties.

PMID- 28511538
TI  - Phonon-like Hydrogen-Bond Modes in Protic Ionic Liquids.
AB  - Gigahertz- to terahertz-frequency infrared and Raman spectra contain a wealth of
      information concerning the structure, intermolecular forces, and dynamics of
      ionic liquids. However, these spectra generally have a large number of
      contributions ranging from slow diffusional modes to underdamped librations and
      intramolecular vibrational modes. This makes it difficult to isolate effects such
      as the role of Coulombic and hydrogen-bonding interactions. We have applied far
      infrared and ultrafast optical Kerr effect spectroscopies on carefully selected
      ions with a greater or lesser degree of symmetry in order to isolate spectral
      signals of interest. This has allowed us to demonstrate the presence of
      longitudinal and transverse optical phonon modes and a great similarity of
      alkylammonium-based protic ionic liquids to liquid water. The data show that such
      phonon modes will be present in all ionic liquids, requiring a reinterpretation
      of their spectra.

PMID- 28511537
TI  - Terminal Acetylated/Acrylated Poly(ethylene glycol) Fabricated Drug Carriers:
      Design, Synthesis, and Biological Evaluation.
AB  - The simple acetylation or acrylation of poly(ethylene glycol) (PEG) terminus
      leads to the aggregation of PEG chains into spherical nanoparticles in water at
      room temperature and very low concentrations. The experiment results suggest that
      this aggregation happens by the variation of the local conformation of the O-CH2
      CH2-O segments of PEG chains caused by the introduced acyl group, which disturbs
      the originally strict hydrogen bond mode between the O-CH2-CH2-O groups and the
      water molecules. The simple modified PEG nanoparticles are excellent carriers for
      drug delivery. As examples, the cross-linkable 1d-based drug delivery systems,
      cPEG@SN-38 and targeted cPEG@SN-38, are successfully established by their high
      drug loading content (18 wt %/wt) and enhanced anticancer efficacy both in vitro
      and in vivo while obviating the inherent toxicity of the employed
      chemotherapeutics. This strategy that revolves around the simple modification of
      the generally regarded as safe (GRAS) modules to fabricate drug carriers
      represents a new direction for the drug delivery systems with clinical potential.

PMID- 28511539
TI  - Exploiting Salt Induced Microphase Separation To Form Soy Protein Microcapsules
      or Microgels in Aqueous Solution.
AB  - Self-assembly of native glycinin at room temperature was investigated as a
      function of the pH and the NaCl concentration. Microphase separation leading to
      the formation of dense protein microdomains was observed by confocal laser
      scanning microscopy. Depending on the conditions, the microdomains coalesced into
      a continuous protein rich phase or associated into large clusters. Addition of
      beta-conglycinin inhibited phase separation and reduced the pH range in which it
      occurred. Microdomains of glycinin that were formed in the presence of 0.1 M NaCl
      transformed into hollow stable cross-linked microcapsules when heated above 60 
      degrees C with diameters between 3 and 30 MUm depending on the protein
      concentration and a shell thickness between 1.0 and 1.4 MUm. The microcapsules
      were stable to dilution in salt free water, whereas microdomains formed at room
      temperature redispersed. Microdomains formed in mixtures with beta-conglycinin
      did not transform into microcapsules, but they became stable cross-linked
      homogeneous microgels.

PMID- 28511540
TI  - Effects of Water-Extractable Arabinoxylan on the Physicochemical Properties and
      Structure of Wheat Gluten by Thermal Treatment.
AB  - This study investigated the effects of water-extractable arabinoxylan (WEAX) on
      gluten by thermal treatment. Fourier transform infrared spectroscopy (FTIR)
      results showed that heating significantly decreased beta-sheets and beta-turn
      structures in gluten proteins between 25 and 55  degrees C. The addition of WEAX
      caused a transition from beta-turn to beta-sheets at >55  degrees C. The ratio of
      weakly hydrogen-bonded beta-sheets to strongly hydrogen-bonded beta-sheets
      demonstrated an increasing trend with temperature increasing, but WEAX can hinder
      this process. FT-Raman results revealed that a hydrophilic environment was
      developed with 5% WEAX at 25  degrees C, and phenolic hydroxyl on ferulic acid
      can form new H-bonds with the phenyl groups of the nondissociated Tyr residues. A
      5% WEAX content is helpful for gluten to maintain its original gauche-gauche
      gauche conformation of disulfide bond upon heating. In addition, WEAX can reduce
      the elasticity of gluten and form a soft texture at 25, 55, and 75  degrees C.

PMID- 28511543
TI  - Sterilization, hydration-dehydration and tube fabrication of zwitterionic
      hydrogels.
AB  - Terminal sterilization of hydrogel-based biomaterials is crucial for their
      clinically relevant applications. The authors synthesized nonfouling zwitterionic
      hydrogels consisting of carboxybetaine (CB) acrylamide monomer and a
      carboxybetaine dimethacrylate crosslinker. The mechanical and biological
      stability of nonfouling hydrogels were investigated using three main terminal
      sterilization techniques, i.e., steam autoclave, ethylene oxide gas, and gamma
      irradiation. It was found that CB hydrogels are very stable at high temperature
      and pressure and in oxidative gas environments without changing their stress,
      modulus, and nonfouling properties. Gamma irradiation of CB hydrogels in dry
      state showed high mechanical and nonfouling stability by avoiding the adverse
      effect of the free radicals resulted from water inside the hydrogel network. The
      CB hydrogels can be dehydrated and hydrated back and forward reversibly in
      several cycles without any loss in mechanical properties, which is desirable for
      hydrogel storage, handling, and sterilization. The CB hydrogel tubes are easily
      prepared using a simple procedure, and they are uniformly transparent and tough
      after swelling. Furthermore, the good mechanical properties of the CB hydrogel
      tubes and their resistance to red blood cells indicate great potential of this
      nonfouling material for medical applications.

PMID- 28511544
TI  - Structural characterization of membrane-bound human immunodeficiency virus-1 Gag
      matrix with neutron reflectometry.
AB  - The structural characterization of peripheral membrane proteins represents a
      tremendous challenge in structural biology due to their transient interaction
      with the membrane and the potential multitude of protein conformations during
      this interaction. Neutron reflectometry is uniquely suited to address this
      problem because of its ability to structurally characterize biological model
      systems nondestructively and under biomimetic conditions that retain full protein
      functionality. Being sensitive to only the membrane-bound fraction of a water
      soluble peripheral protein, neutron reflectometry obtains a low-resolution
      average structure of the protein-membrane complex that is further refined using
      integrative modeling strategies. Here, the authors review the current
      technological state of biological neutron reflectometry exemplified by a detailed
      report on the structure determination of the myristoylated human immunodeficiency
      virus-1 (HIV-1) Gag matrix associated with phosphoserine-containing model
      membranes. The authors found that the HIV-1 Gag matrix is able to adopt different
      configurations at the membrane in a pH-dependent manner and that the myristate
      group orients the protein in a way that is conducive to PIP2-binding.

PMID- 28511546
TI  - The Relationship Between Work Commitment, Dynamic, and Medication Error.
AB  - Incidence of medication errors in intensive care unit (ICU) can cause irreparable
      damage for ICU patients. Therefore, it seems necessary to find the causes of
      medication errors in this section. Work commitment and dynamic might affect the
      incidence of medication errors in ICU. To assess the mentioned hypothesis, we
      performed a descriptive-analytical study which was carried out on 117 nurses
      working in ICU of educational hospitals in Tehran. Minick et al., Salyer et al.,
      and Wakefield et al. scales were used for data gathering on work commitment,
      dynamic, and medication errors, respectively. Findings of the current study
      revealed that high work commitment in ICU nurses caused low number of medication
      errors, including intravenous and nonintravenous. We controlled the effects of
      confounding variables in detection of this relationship. In contrast, no
      significant association was found between work dynamic and different types of
      medication errors. Although the study did not observe any relationship between
      the dynamics and rate of medication errors, the training of nurses or nursing
      students to create a dynamic environment in hospitals can increase their interest
      in the profession and increase job satisfaction in them. Also they must have
      enough ability in work dynamic so that they don't confused and distracted result
      in frequent changes of orders, care plans, and procedures.

PMID- 28511545
TI  - Fosfomycin tromethamine for the Treatment of Cystitis in Abdominal Solid Organ
      Transplant Recipients With Renal Dysfunction.
AB  - BACKGROUND: Urinary tract infection (UTI) after abdominal solid organ
      transplantation (SOT) is associated with significant morbidity and mortality.
      Fosfomycin tromethamine (FOS), a uroselective antibiotic, is FDA approved for
      uncomplicated UTIs in women and is used off-label for complicated UTIs and
      prostatitis in men. Literature supporting the use of FOS in the SOT population is
      limited, and efficacy is questioned in the setting of renal dysfunction.
      OBJECTIVE: To evaluate the success of FOS for the treatment of cystitis in SOT
      patients with renal dysfunction. METHODS: This was a single-center, retrospective
      study using medical records. SOT recipients receiving at least 1 dose of FOS for
      treatment of cystitis between January 1, 2009, and April 30, 2015, were included.
      Treatment outcomes were analyzed with respect to renal function. RESULTS: A total
      of 76 courses of FOS were identified in 64 patients. The renal dysfunction arm
      (creatinine clearance [CrCl] < 40 mL/min) included 33 patients with 39 FOS
      courses; the normal renal function arm (CrCl >= 40 mL/min) included 31 patients
      with 37 FOS courses. Mean CrCl was 23.3 +/- 9.7 mL/min for the renal-dysfunction
      group and 65 +/- 29.3 mL/min for the normal renal function group ( P < 0.01). No
      significant difference in treatment success was noted between CrCl <40 mL/min and
      CrCl >=40 mL/min (31 [80%] vs 34 [92%], P = 0.12) in a unilateral analysis. After
      adjusting for confounders in a multivariable analysis, there was no difference in
      the risk of failure between CrCl <40 mL/min and CrCl >=40 mL/min groups ( P =
      0.70). CONCLUSION: FOS appears to be successful for the treatment of cystitis in
      SOT recipients in the setting of renal dysfunction.

PMID- 28511548
TI  - Quality-adjusted life year difference in patients with predominant negative
      symptoms of schizophrenia treated with cariprazine and risperidone.
AB  - AIM: Our study aimed at estimating differences in quality-adjusted life year
      (QALY) gain for patients with predominant negative symptoms of schizophrenia
      treated with cariprazine compared with risperidone. MATERIALS & METHODS: A Markov
      model was built, based on the Mohr-Lenert approach and data derived from clinical
      trials, to estimate potential QALY gains of patients. RESULTS: Patients had
      higher probability of reaching better health states treated with cariprazine
      compared with risperidone. In the model, this resulted in an estimated QALY gain
      of 0.029 per patient, after 1 year of treatment. CONCLUSION: Cariprazine, which
      showed clinically meaningful improvement in the symptoms, and personal and social
      performance, can also provide significant QALY gain in the treatment of patients
      with predominant negative symptoms of schizophrenia compared with risperidone.

PMID- 28511547
TI  - Smell and Taste Impairment After Total Laryngectomy.
AB  - OBJECTIVE: Aim of this observational study is the evaluation of olfactory and
      gustatory impairments in laryngectomized long-term survivors compared to control
      subjects. Correlation between smell and taste alterations, age, and previous
      adjuvant treatments in laryngectomees was investigated. METHODS: Fifty control
      subjects and 50 patients who underwent total laryngectomy for advanced laryngeal
      carcinoma were evaluated. All subjects underwent symptoms evaluation,
      oropharyngeal exam, endoscopic fiberoptic nasal examination, and Taste Strips and
      Sniffin' Sticks tests. RESULTS: Hyposmia was reported by all laryngectomees and
      hypogeusia by 54% of patients. Sniffin' Sticks and Taste Strips tests
      demonstrated a statistically significant difference between controls and
      laryngectomees regarding olfactory threshold, odor discrimination and
      identification, Threshold Discrimination Identification (TDI) score, and sour,
      salty, and gustatory Total Taste score ( P < .05). Multivariate analysis for
      Total Taste score in laryngectomees showed a statistically significant
      correlation with aging, having an odds ratio of 0.127 for age >=65 years, but not
      with TDI score, radiotherapy, and follow-up time, whereas multivariate analysis
      for TDI score demonstrated no correlation with radiotherapy, age, and follow-up
      time. CONCLUSIONS: Total laryngectomy determines olfactory and gustatory
      impairments that should be taken into account in clinical practice. Relationships
      between sensorial alterations, aging, follow-up period, and adjuvant treatments
      should be further evaluated in prospective studies.

PMID- 28511550
TI  - CT features in surgically proven cases of ovarian torsion-a pictorial review.
AB  - Ovarian torsion is a surgical emergency characterized by a partial or complete
      rotation of the ovarian vascular pedicle, causing obstruction to venous outflow
      followed by arterial inflow. Clinically, ovarian torsion frequently mimics other
      causes of acute pelvic pain such as appendicitis, diverticulitis, renal colic
      etc. Ultrasonography is the first-line imaging modality of choice for evaluation
      of ovarian torsion. MRI is useful as a problem-solving tool in patients with
      equivocal or non-diagnostic ultrasonography studies. CT is ordinarily not
      utilized in a young female with suspected ovarian torsion due to the radiation
      dose. However, the significant expansion in use of CT imaging in emergency
      departments for female patients presenting with acute abdominal pain has
      increased the likelihood that ovarian torsion may be first seen on CT. In
      addition, a non-specific clinical presentation may lead to an initial imaging
      with CT rather than ultrasonography. Ultrasound features of the ovarian torsion
      are well known and sufficiently described across literature as compared with the
      CT scan findings. In view of the increasing usage of CT as the modality of choice
      in emergency settings, it is imperative for the radiologist to familiarize with
      the CT features of ovarian torsion. An early correct diagnosis by the radiologist
      in clinically unsuspected cases, facilitating a prompt surgery to restore the
      ovarian blood flow can prevent permanent irreversible damage. There is limited
      published data available on the CT features of ovarian torsion. This pictorial
      essay illustrates CT findings with histological correlation of surgically proven
      ovarian torsion in our institution. These patients were primarily investigated
      with CT scan for acute pelvic pain ascribed to non-gynaecological causes such as
      bowel or urinary tract lesions.

PMID- 28511549
TI  - Radiological findings on irradiation-CT in patients with non metastatic breast
      cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the number of incidental
      findings on native CT treatment-planning scans for radiation in breast cancer
      patients. METHODS: The treatment-planning scans of 382 patients with non
      metastatic breast cancer were retrospectively analyzed for additional findings.
      The planning scan area covered the entire thorax and the upper part of the
      abdomen. Incidental findings were classified according to their clinical
      relevance. RESULTS: Overall 892 incidental findings were detected in the CT
      treatment-planning scans (mean 2.34 findings per patient). Only a small
      proportion of patients (n = 63, 16.4%) had no finding. Most findings were located
      in the thorax (683, 76.57%), and 209 findings (23.43%) were abdominal. 79
      findings (8.87%) were of major clinical relevance, 232 findings (26.01%) were of
      moderate clinical relevance and 580 findings (65.02%) were of minor clinical
      relevance. Most clinically relevant findings were in the thorax (p = 0.006).
      Abdominal findings were more of significantly minor clinical relevance (p <
      0.0001). CONCLUSION: Radiological findings are frequent in native CT treatment
      planning scans for radiation of breast cancer patients. Therefore, the
      radiologist should use this performed sectional image to obtain additional
      information of the patient. Advances in knowledge: Treatment-planning CT scans
      can show several radiological findings, namely 2.34 findings per patient. Major
      clinically relevant findings account for 8.87%.

PMID- 28511551
TI  - Theoretical Foundations of Appeals Used in Alcohol-Abuse and Drunk-Driving Public
      Service Announcements in the United States, 1995-2010.
AB  - PURPOSE: The study identifies the extent to which theoretical constructs drawn
      from well-established message effect communication theories are reflected in the
      content of alcohol-related public service announcements (PSAs) airing in the
      United States over a 16-year period. DESIGN: Content analysis of 18 530 141
      alcohol-abuse (AA) and drunk-driving (DD) PSAs appearing on national network and
      local cable television stations in the 210 largest designated marketing areas
      (DMAs) from January 1995 through December 2010. MEASURES: The authors developed a
      detailed content analytic codebook and trained undergraduate coders to reliably
      identify the extent to which theoretical constructs and other creative ad
      elements are reflected in the PSAs. We show these patterns using basic
      descriptive statistics. RESULTS: Although both classes of alcohol-related PSAs
      used strategies that are consistent with major message effect theories, their
      specific theoretical orientations differed dramatically. The AA PSAs were
      generally consistent with constructs emphasized by the Extended Parallel Process
      Model (EPPM), whereas DD PSAs were more likely to use normative strategies
      emphasized by the Focus Theory of Narrative Conduct (FTNC) or source credibility
      appeals central to the Elaboration Likelihood Model. CONCLUSION: Having
      identified message content, future research should use deductive approaches to
      determine if volume and message content of alcohol-control PSAs have an impact on
      measures of alcohol consumption and/or measures of drunk driving, such as
      fatalities or driving while intoxicated/driving under the influence arrests.

PMID- 28511552
TI  - R147W in PROC Gene Is a Risk Factor of Thromboembolism in Thai Children.
AB  - The p.R147W mutation, the c.C6152T in exon 7, causing a change in amino acid from
      arginine to tryptophan of the PROC gene has been reported as a common mutation in
      Taiwanese populations with venous thromboembolism (VTE). The present study aimed
      to identify the prevalence of p.R147W in the Thai population and children with TE
      and the risk of developing TE. Patients aged <=18 years diagnosed with TE were
      enrolled. The PROC gene was amplified by polymerase chain reaction using a
      specific primer in exon 7. The restriction fragment length polymorphism was
      designed using MwoI restriction enzyme. A total of 184 patients and 690 controls
      were enrolled. The most common diagnosis of TE was arterial ischemic stroke
      (AIS), at 100 (54.3%), followed by VTE, at 38 (20.6%), and cerebral venous sinus
      thrombosis (CVST), at 23 (12.5%). The prevalence of heterozygous and homozygous
      p.R147W in patients and controls was 9.5% versus 5.8% and 2.7% versus 0.1%,
      respectively. Heterozygous p.R147W had odds ratios (ORs) of 1.8 (95% confidence
      interval [CI]: 1.0-3.2, P = .04), 3.2 (95% CI: 1.2-8.2, P = .009), and 4.5 (95%
      CI: 1.6-12.8, P = .002) of developing overall TE, VTE, and CVST, respectively.
      Homozygous p.R147W had ORs of 20.2 (95% CI: 2.3-173.7, P < .001), 21.4 (95% CI:
      2.2-207.9, P < .001), and 43.3 (95% CI: 3.8-490.6, P < .001) of developing
      overall TE, AIS, and CVST, respectively. This study suggested that p.R147W is a
      common mutation and increased risk of TE in Thai children.

PMID- 28511553
TI  - Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty
      After Tooth Extraction in Patients Receiving Antiplatelet Therapy.
AB  - When patients on antiplatelet therapy (APT) require minor invasive surgery, APT
      is usually continued to limit the risk of thrombosis. However, the possibility of
      hemostatic difficulties necessitates the monitoring of platelet aggregation to
      prevent unexpected bleeding. We examined whether whole blood aggregometry as a
      point-of-care testing (POCT) could be useful as a tool for predicting hemostatic
      difficulties. Sixty-five patients receiving APT and 15 patients who were not
      receiving APT were enrolled in the present study; all patients were scheduled to
      undergo a tooth extraction. Whole blood samples were obtained and were examined
      using multiple electrode aggregometry. The aggregometry was performed using
      arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor
      activating peptide. Hemostatic difficulty was defined as a need for more than 10
      minutes of compression to achieve hemostasis. The AA test results were
      significantly lower in patients treated with aspirin (control: 97.7 [29.0] U,
      aspirin: 14.5 [7.2] U, P < .001). The ADP test results were also significantly
      lower in patients treated with a P2Y12 inhibitor (control: 77.7 [21.7] U, P2Y12
      inhibitor: 37.3 [20.4] U, P < .01). Six of the examined cases exhibited
      hemostatic difficulties. The cutoff values for the prediction of hemostatic
      difficulty were 16.5 U for the AA test (sensitivity, 0.833; specificity, 0.508)
      and 21 U for the ADP test (sensitivity, 0.847; specificity, 0.500). Our study
      showed that whole blood aggregometry was useful as a POCT for the prediction of
      hemostatic difficulties after tooth extraction in patients receiving APT.

PMID- 28511554
TI  - Resveratrol promotes recovery of immune function of immunosuppressive mice by
      activating JNK/NF-kappaB pathway in splenic lymphocytes.
AB  - Resveratrol, a natural compound found in over 70 plants, is known to possess
      immunoregulatory effects and anti-inflammatory activity. It has been shown that
      resveratrol has regulatory effects on different signaling pathways in different
      diseases. However, few reports have evaluated the effects of resveratrol on
      reinforcing immunity recovery via activating nuclear factor-kappaB (NF-kappaB)
      pathway and Jun N-terminal kinases (JNK) pathway. The present study aimed to
      assess immune-enhancing activity and underlying mechanism of resveratrol in
      immunosuppressive mice. Previously, we reported that resveratrol could promote
      mouse spleen lymphocyte functions to recover the immune system effectively. In
      the present study, we show that resveratrol could upregulate the expressions of
      NF-kappaB, IkappaB kinase, JNK, and c-jun in splenic lymphocytes of
      immunosuppressive mice. Taken together, our results indicate that resveratrol
      could promote recovery of immunologic function in immunosuppressive mice by
      activating JNK/NF-kappaB pathway.

PMID- 28511557
TI  - Impact of a Perioperative Prophylaxis Guideline on Post-Cardiothoracic Surgery
      Atrial Fibrillation.
AB  - BACKGROUND: National practice guidelines do not provide clear recommendations on
      combination pharmacological regimens to reduce cardiothoracic surgery (CTS)
      postoperative atrial fibrillation (POAF). OBJECTIVE: This study examines if there
      is a reduction in POAF rates after implementing a perioperative prophylaxis
      guideline that includes amiodarone, beta-blockers, and high-intensity statins.
      METHODS: Data were retrospectively collected on 400 adults (200 patients pre
      guideline implementation and 200 patients post-guideline implementation) with a
      CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus, and
      Vascular Disease) score of at least 3 points after CTS. Data were collected on
      the incidence of POAF lasting more than 5 minutes and secondary outcomes,
      including the length of hospitalization, guideline adherence rate, adverse
      events, and timeliness of POAF treatment. RESULTS: Guideline implementation
      increased prophylactic amiodarone ( P < 0.0001), statin ( P = 0.029), and high
      intensity statin ( P = 0.002) use without changing beta-blocker use (64.5% vs
      67.0%, P = 0.673) and reduced POAF (39.5% vs 52.0%, P = 0.016) and ventricular
      tachycardia (15.5% vs 24.5%, P = 0.034) compared with preguideline rates. Length
      of hospitalization and other postoperative adverse events, including stroke and
      mortality, were not statistically different. Subgroup analyses of patients who
      were adherent to both the amiodarone and beta-blocker recommendations (28% of the
      total) or to all 3 recommended therapies (24% of the total) had significant
      decreases in POAF ( P = 0.001; P < 0.001), length of hospitalization ( P = 0.023;
      P = 0.049), length of intensive care unit stay ( P = 0.045; P = 0.040), and
      ventricular tachycardia ( P = 0.008; P = 0.017) compared with preguideline
      patients, respectively. CONCLUSIONS: A perioperative guideline of amiodarone,
      beta-blockers, and high-intensity statins reduced POAF, but better benefits may
      result from enhanced adherence.

PMID- 28511558
TI  - Three new indole alkaloid derivatives from the roots of Murraya paniculata.
AB  - Three new indole alkaloid derivatives, named paniculidines D-F (1-3), and six
      known analogs (4-9) were isolated from the roots of Murraya paniculata. The
      structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR
      spectroscopic data analysis and comparison with the data reported in literature.
      The absolute configurations of new compounds were assigned via the determination
      of specific optical rotation, Mosher's method, and ECD spectra. Compound 3 is the
      first heterodimer of C-N linked indole and coumarin derivatives.

PMID- 28511556
TI  - Performance and digestive function of broiler chickens given grit in the diet.
AB  - 1. A series of experiments were carried out to study the effect of grit on
      broiler performance, gizzard development and fate of grit in the digestive tract.
      2. In Experiment 1, performance, gizzard weight and content of grit in the
      gizzard of broiler chickens given access to granite-type grit was investigated.
      In Experiment 2, the effect of grit stones on performance and gizzard development
      was assessed in diets with or without whole wheat. 3. In Experiment 3, the effect
      of grit in the form of zeolite, granite or marble on gizzard development and
      digestive tract grinding and passage was studied in diets with or without whole
      wheat. 4. Grit stones had no effect on performance of broiler chickens, which may
      be explained by the fact that grit stones did not stimulate gizzard development
      to the same extent as with other structural materials. 5. The lack of stimulation
      is at least partly due to the fact that a majority of the grit stones eaten pass
      through the small intestine without being retained in the gizzard. 6. Grit in the
      form of marble reduced feed intake and weight gain.

PMID- 28511559
TI  - Migrating microbes: what pathogens can tell us about population movements and
      human evolution.
AB  - BACKGROUND: The biology of human migration can be observed from the co
      evolutionary relationship with infectious diseases. While many pathogens are
      brief, unpleasant visitors to human bodies, others have the ability to become
      life-long human passengers. The story of a pathogen's genetic code may,
      therefore, provide insight into the history of its human host. The evolution and
      distribution of disease in Africa is of particular interest, because of the deep
      history of human evolution in Africa, the presence of a variety of non-human
      primates, and tropical reservoirs of emerging infectious diseases. METHODS: This
      study explores which pathogens leave traces in the archaeological record, and
      whether there are realistic prospects that these pathogens can be recovered from
      sub-Saharan African archaeological contexts. RESULTS: Three stories are then
      presented of germs on a journey. The first is the story of HIV's spread on the
      back of colonialism and the railway networks over the last 150 years. The second
      involves the spread of Schistosoma mansoni, a parasite which shares its history
      with the trans-Atlantic slave trade and the origins of fresh-water fishing.
      Finally, we discuss the tantalising hints of hominin migration and interaction
      found in the genome of human herpes simplex virus 2. CONCLUSIONS: Evidence from
      modern African pathogen genomes can provide data on human behaviour and migration
      in deep time and contribute to the improvement of human quality-of-life and
      longevity.

PMID- 28511560
TI  - Synthesis and in vitro antitumour activities of lupeol derivatives.
AB  - Nine lupeol derivatives were synthesised and assayed in vitro for their
      antitumour activities against three human tumour cells lines, A549, LAC and
      HepG2. Of lupeol derivaties, six were new compounds, and five compounds against
      A549 cells, four compounds against HepG2 cells and three compounds against LAC
      cells were effective in reducing viability, and the most promising compounds 5, 6
      and 9 exhibited high activities against lung and liver cancer cells, even higher
      activities than those of adriamycin.

PMID- 28511561
TI  - Depression of the maxillary sinus anterior wall and its influence on panoramic
      radiography appearance.
AB  - OBJECTIVES: To clarify the depression aspect of the maxillary sinus anterior wall
      and to investigate its relationship with the panoramic image appearance of a
      diagonal line from the inferior part of the so-called panoramic innominate line
      to the medial portion of the orbital floor line. METHODS: Based on CT data,
      panoramic images were simulated for two typical cases with and without anterior
      wall depression. Next, on axial CT images of 1689 subjects (3378 sinuses) stored
      in our image database, the wall depths were measured and analyzed for their
      relationships with the panoramic appearances of the diagonal line, classified
      into invisible, obscure and clear patterns. RESULTS: Based on the simulation
      study, visualization of the diagonal line was verified to alter depending on the
      morphology of the anterior wall and the position of the panoramic image layer. In
      408 (12.1%) sinuses, the diagonal line (clear and obscure patterns) could be seen
      on the panoramic image. The incidences of the obscure and clear patterns
      increased with increasing age groups. The mean wall depths were 2.91, 4.80 and
      7.28 mm for the invisible, obscure and clear patterns, respectively. The clear
      pattern showed the highest value for the wall depth, followed by the obscure
      pattern. CONCLUSIONS: The diagonal line on a panoramic image was verified to be
      related to depression of the maxillary sinus anterior wall, and its panoramic
      image appearance can be altered depending on the position of the tomographic
      image layer.

PMID- 28511562
TI  - A review of cognitive remediation approaches for schizophrenia: from top-down to
      bottom-up, brain training to psychotherapy.
AB  - INTRODUCTION: Individuals with psychotic disorders experience profound impairment
      in neurocognition, which is consistently found to be the best predictor of
      independent community functioning. Several diverse behavioural treatments
      designed to enhance neurocognitive abilities have been developed, with subtle to
      stark differences among them. Various approaches, to varying degrees, have
      demonstrated success across diffuse outcomes: improved brain structure and
      function, performance on neuropsychological tests, and community activities
      associated with daily living. Areas covered: This paper reviews the different
      approaches to cognitive remediation and the differential effects these approaches
      have on neurophysiological function, neurocognitive abilities, and real-world
      community functioning. Cognitive remediation approaches can be broadly classified
      along two dimensions: 1) treatment target, and 2) treatment modality. Some
      approaches target more basic perceptual skills, some target higher level
      executive processes, while some are non-targeted and seek to improve general
      cognitive ability. With regard to modality, approaches might have little/no
      therapist involvement and rely exclusively on computerized practice or they may
      include intensive therapist involvment to generalize neurocognitive change to
      community functioning. Expert commentary: Compared to other widely implemented
      treatments for schizophrenia, cognitive remediation produces better effects on
      outcome measures. It is time for cognitive remediation to be adopted as a best
      practice in the treatment of schizophrenia.

PMID- 28511563
TI  - Authors' response: development and validation of a questionnaire to evaluate
      infection control in oral radiology-consistent statistical analyses and
      methodology.

PMID- 28511564
TI  - Head and neck effective dose and quantitative assessment of image quality: a
      study to compare cone beam CT and multislice spiral CT.
AB  - OBJECTIVES: To evaluate the effective dose and image quality of horizontal CBCT
      in comparison with multislice spiral CT (MSCT) in scans of the head, cervical
      spine, ear and dental arches. METHODS: A head and neck Alderson-Rando(r) phantom
      (The Phantom Laboratory, Salem, NY) equipped with 74 thermoluminescence
      dosemeters was exposed according to 5 different scans in CBCT and 4 different
      scans in MSCT. Spatial and contrast resolutions, in terms of modulation transfer
      function and contrast-to-noise ratio (CNR), were measured to obtain a
      quantitative assessment of image quality. RESULTS: The CBCT effective dose was
      248, 249, 361, 565 and 688 uSv in the cervical spine, head, ear, dental arches
      with small field of view and dental arches with medium field of view,
      respectively. The MSCT effective dose was 3409, 1892, 660 and 812 uSv in the
      cervical spine, head, ear and dental arches, respectively. The modulation
      transfer function was 0.895 vs 0.347, 0.895 vs 0.275, 0.875 vs 0.342 and 0.961 vs
      0.352 for CBCT vs MSCT in the cervical spine, head, ear and dental arches,
      respectively. Head and cervical spine MSCT showed greater CNR than CBCT, whereas
      CNR of the ear and dental arches showed comparable values. CONCLUSIONS: CBCT was
      preferable to MSCT for the ear and dental arches volumetric imaging due to its
      lower radiation dose and significantly higher spatial resolution. In the case of
      cervical spine and head imaging, MSCT should be generally recommended if a high
      contrast resolution is required, despite the greater radiation exposure.

PMID- 28511565
TI  - The role of membrane transporters in ovarian cancer chemoresistance and
      prognosis.
AB  - INTRODUCTION: Ovarian cancer has the highest mortality rate of all cancers in
      women. There is currently no effective method for early diagnosis, limiting the
      precision of clinical expectations. Predictions of therapeutic efficacy are
      currently not available either. Specifically, the development of chemoresistance
      against conventional chemotherapy poses a fundamental complication. Some membrane
      transporters have been reported to influence chemoresistance, which is often
      associated with a poor prognosis. Areas covered: The aim of this article is to
      review the existing information about membrane transporters and their role in
      both ovarian cancer chemoresistance and its outcomes. We then highlight
      limitations of current methodologies and suggest alternatives providing avenues
      for future research. Expert opinion: Membrane transporters play an important role
      in development of chemoresistance and affect prognosis of ovarian cancer
      patients; however, due to variations in methodology and in patient populations,
      their specific roles have yet to be clarified. For further evaluation of the
      clinical utility of membrane transporters, it is essential to validate results
      and improve methods for marker assessment across laboratories. A promising area
      for future research is to identify the genetic variability in potential markers
      in peripheral blood. These markers would then stratify patients into defined
      groups for optimal intervention.

PMID- 28511567
TI  - Treating the chronic-phase chronic myeloid leukemia patient: which TKI, when to
      switch and when to stop?
AB  - INTRODUCTION: With the discovery of imatinib mesylate nearly 20 years ago,
      tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid
      leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has
      served as a paradigm of success for targeted drug therapy in cancer. Several new
      TKIs for CML have been approved over the last two decades that exhibit improved
      potency over imatinib and have different off-target profiles, providing options
      for individualized therapy selection. Areas covered: Current management of
      chronic phase CML, including guidance on the sequential use of imatinib and newer
      generation TKIs and evolving treatment strategies such as TKI discontinuation.
      Relevant literature was identified by searching biomedical databases (i.e.
      PubMed) for primary research material. Expert commentary: Although survival
      outcomes have drastically improved for CML patients, treatment for CML has grown
      more complex with the introduction of next-generation TKIs and the advent of
      treatment-free remissions (TFR). Goals of therapy have shifted accordingly, with
      increased focus on improving quality of life, managing patient expectations and
      optimizing patient adherence.

PMID- 28511566
TI  - Polar steroid derivatives from the Vietnamese starfish Astropecten polyacanthus.
AB  - Five polar steroid derivatives, including one new glycosylated polyhydroxysteroid
      namely polyacanthoside A (1), were isolated from the water-soluble materials from
      the MeOH extract of the Vietnamese starfish Astropecten polyacanthus using
      various chromatographic separations. The structure elucidation was confirmed by
      spectroscopic experiments such as HR-ESI-MS, 1D and 2D NMR. Among the isolated
      compounds, (20R,24S)-3beta,6alpha,8,15beta,24-pentahydroxy-5alpha-cholestane (3)
      showed significant cytotoxic effect against five human cancer cell lines as
      HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC50 values from 18.03 +/- 2.63 to
      21.59 +/- 3.23 MUM.

PMID- 28511568
TI  - Flexor Tendon Ruptures After Distal Scaphoid Excision for Scaphotrapeziotrapezoid
      Osteoarthritis.
AB  - BACKGROUND: Distal scaphoid excision is one treatment option for osteoarthritis
      of the scaphotrapeziotrapezoid (STT) joint following failure of conservative
      measures. Potential complications of this procedure include injury to the carpal
      ligaments, cartilage, and radial artery. METHODS: A single case was identified by
      the senior author, and the medical record was reviewed for surgical notes,
      progress notes, and radiographs. RESULTS: A 68-year-old male sustained ruptures
      of the flexor digitorum superficialis (FDS) and flexor digitorum profundus to the
      index finger 3 years following a distal scaphoid excision for symptomatic STT
      osteoarthritis. He required a flexor tendon reconstruction using the remaining
      FDS tendon for graft incorporated with a Pulvertaft weave. His midcarpal pain
      continued after recovery of his index finger function, eventually requiring a 4
      corner fusion of the wrist. CONCLUSIONS: Flexor tendon rupture is a previously
      unreported complication of distal scaphoid excision for STT arthritis.

PMID- 28511569
TI  - Weightbearing vs Gravity Stress Radiographs for Stability Evaluation of
      Supination-External Rotation Fractures of the Ankle.
AB  - BACKGROUND: Isolated lateral malleolar fractures may result from a supination
      external rotation (SER) injury of the ankle. Stable fractures maintain tibiotalar
      congruence due to competent medial restraints and can be treated nonoperatively
      with excellent functional results and long-term prognosis. Stability might be
      assessed with either stress radiographs or weightbearing radiographs. METHODS: A
      consecutive series of patients with closed SER fractures (presumed AO 44-B1) were
      prospectively enrolled from 2008 to 2015. Patients with clearly unstable
      fractures (medial clear space more than 7 mm) on the initial nonweightbearing
      radiograph were excluded and operated on. All other patients were examined with a
      gravity stress and a weightbearing anteroposterior radiograph. Borderline
      instability of the fracture was assumed when the medial clear space was 4 to 7
      mm. Those were treated nonoperatively. RESULTS: Of 104 patients with isolated
      lateral malleolar fractures of the SER type, 14 patients were treated operatively
      because of clear instability (displacement) on the initial radiographs. Of the
      nonoperative patients, 44 patients demonstrated borderline instability on the
      gravity stress but stability on the weightbearing radiograph ("gravity
      borderline"); the remaining 46 were stable in both tests ("gravity stable"). At
      an average follow-up of 23 months, no significant differences were seen in the
      American Orthopaedic Foot & Ankle Society hindfoot score (92 points gravity
      borderline group vs 93 points gravity-unstable group), the Foot Functional Index
      score (11 vs 10 points), the Short Form 36 (SF-36) physical component (86 vs 85
      points), and SF-36 mental component (84 vs 81 points). Radiographically, all
      fractures had healed with anatomic congruity of the ankle. CONCLUSION:
      Weightbearing radiographs provided a reliable basis to decide about stability and
      nonoperative treatment in isolated lateral malleolar fractures of the SER type
      with excellent clinical and radiographic outcome at short-term follow-up. Gravity
      stress radiographs appear to overrate the need for operative treatment. LEVEL OF
      EVIDENCE: Level III, prospective comparative study.

PMID- 28511570
TI  - Carpal Tunnel Syndrome Following Corrective Osteotomy for Distal Radius Malunion:
      A Rare Case Report and Review of the Literature.
AB  - BACKGROUND: Although median nerve neuropathy and carpal tunnel syndrome (CTS) are
      known complications of both untreated and acutely treated distal radius fracture,
      median neuropathy after correction of distal radius malunion is not commonly
      reported in hand surgery literature. We describe a patient with severe CTS after
      corrective osteotomy, open reduction internal fixation (ORIF) with a volar
      locking plate (VLP), and bone grafting for distal radius malunion. METHODS: We
      report a case of severe acute CTS as a complication of corrective osteotomy with
      bone grafting for distal radius malunion. RESULTS: The patient was treated with
      surgical exploration of the median nerve and carpal tunnel release. CONCLUSION:
      The authors report a case of acute CTS after ORIF with VLP for a distal radius
      malunion warranting surgical exploration and carpal tunnel release. Treatment
      teams must be aware of this potential complication so that the threshold for
      reoperation is low and irreversible damage to the median nerve is prevented.

PMID- 28511571
TI  - Brain Injury and Offending: The Development and Field Testing of a Linkworker
      Intervention.
AB  - Evidence suggests that traumatic brain injury (TBI) is more prevalent amongst
      offender populations than in the general population, and that it can lead to
      aggressive behaviour while in custody and impair engagement with offender
      rehabilitation programmes. The aim of this study was to develop, implement, and
      evaluate a brain injury Linkworker approach designed to support prisoners who
      report a significant TBI or multiple mild TBIs. Three clinical case examples are
      reported to illustrate the conceptual foundations of the approach and to
      demonstrate the feasibility of the service. Early results showed that engagement
      with a Linkworker led to effective identification of key areas of intervention
      and resulted in better integration for prisoners while in custody and in
      enhancement of the outcomes of offender rehabilitation. These initial findings
      provide justification for wider implementation and systematic evaluation of the
      efficacy of this model of service.

PMID- 28511573
TI  - Inhibition of PKR ameliorates lipopolysaccharide-induced acute lung injury by
      suppressing NF-kappaB pathway in mice.
AB  - Acute lung injury (ALI) is characterized by dramatic lung inflammation and
      alveolar epithelial cell death. Although protein kinase R (PKR) (double-stranded
      RNA-activated serine/threonine kinase) has been implicated in inflammatory
      response to bacterial cell wall components, whether it plays roles in
      lipopolysaccharide (LPS)-induced ALI remains unclear. This study was aimed to
      reveal whether and how PKR was involved in LPS-induced ALI pathology and the
      potential effects of its specific inhibitor, C16 (C13H8N4OS). During the
      experiment, mice received C16 (100 or 500 ug/kg) intraperitoneally 1 h before
      intratracheal LPS instillation. Then, whole lung lavage was collected for
      analysis of total protein levels and proinflammatory cytokines, including tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6. The
      lungs were tested for Western blot, transferase-mediated dUTP nick-end labeling
      (TUNEL) stain and immunohistochemistry. Results showed that PKR phosphorylation
      increased significantly after LPS instillation. Furthermore, PKR specific
      inhibition attenuated LPS-induced lung injury (hematoxylin and eosin stain),
      reduced lung protein permeability (total protein levels in whole lung lavage) and
      suppressed proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and lung
      apoptosis (TUNEL stain and caspase3 activation). Moreover, mechanism-study showed
      that C16 significantly suppressed I kappa B kinase (IKK)/I kappa B alpha
      (IkappaBalpha)/NF-kappaB signaling pathway after LPS challenge. These findings
      suggested that PKR inhibition ameliorated LPS-induced lung inflammation and
      apoptosis in mice by suppressing NF-kappaB signaling pathway.

PMID- 28511574
TI  - Effects of age and sex on voice onset time: Evidence from Mandarin voiceless
      stops.
AB  - Considerable studies have addressed effects of age and sex on voice onset time
      (VOT) in English. However, few studies have examined these effects on Mandarin
      stops. This study attempts to examine effects of age and sex on VOT in Mandarin.
      A total of 85 Mandarin-speaking children, aged 4-18 years old, and 13 adults as
      reference participated in a production experiment. Productions were elicited by
      reading target words in carrier phrases. Results showed that children aged 6-7
      years old had longer VOTs than older ones for highly aspirated stops, and the
      same tendency was not observed for unaspirated stops. However, no linear
      developmental trend was observed for both highly aspirated and unaspirated stops.
      In addition, females displayed longer VOTs for highly aspirated stops and shorter
      for unaspirated stops, whereas significant sex differences in VOTs existed from
      14 years old to adulthood for highly aspirated stops, and no significant sex
      differences in VOTs were found for unaspirated stops in each group, indicating
      that sex differences in VOTs varied with age and aspiration. The findings suggest
      that physiological changes in and differences between males and females provide
      account for some, but not all differences in VOTs across age and sex.

PMID- 28511575
TI  - Liver Transplantation for Non-Alcoholic Steatohepatitis Related Cirrhosis.

PMID- 28511572
TI  - mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling
      atherosclerosis and vascular cognitive impairment.
AB  - We recently showed that mTOR attenuation blocks progression and abrogates
      established cognitive deficits in Alzheimer's disease (AD) mouse models. These
      outcomes were associated with the restoration of cerebral blood flow (CBF) and
      brain vascular density (BVD) resulting from relief of mTOR inhibition of NO
      release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR
      drives aging and vascular dysfunction is a universal feature of aging, we
      hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction
      associated with atherosclerosis. We measured CBF, BVD, cognitive function,
      markers of inflammation, and parameters of cardiovascular disease in LDLR-/- mice
      fed maintenance or high-fat diet +/- rapamycin. Cardiovascular pathologies were
      proportional to severity of brain vascular dysfunction. Aortic atheromas were
      reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated
      potentially through reduction in systemic and brain inflammation following
      chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular
      integrity and function and that mTOR attenuation may restore neurovascular
      function and cardiovascular health. Together with our previous studies in AD
      models, our data suggest mTOR-driven vascular damage may be a mechanism shared by
      age-associated neurological diseases. Therefore, mTOR attenuation may have
      promise for treatment of cognitive impairment in atherosclerosis.

PMID- 28511576
TI  - Performance of a Brazilian sample on the Portuguese translation of the BNI Screen
      for Higher Cerebral Functions.
AB  - INTRODUCTION: The Barrow Neurological Institute (BNI) Screen for Higher Cerebral
      Functions (BNIS) has been translated into several languages and found useful in
      evaluating multiple domains of cognitive and affective dysfunction, particularly
      in neuro-rehabilitation settings. Normative data from countries with high
      literacy rates have reported strikingly similar mean level of performance scores
      on this test, with age typically correlating higher with total score performance
      than education. In the present study, we obtain convenience sample normative data
      from a native Brazilian population on a Portuguese translation of the BNIS (i.e.,
      BNIS-PT). METHOD: The BNIS was translated into Portuguese by two native speaking
      Portuguese neuropsychologists who were also fluent in English. It was then
      administered to 201 normally functioning native Brazilian individuals who varied
      considerably in age and formal educational training. RESULTS: The mean BNIS total
      score was similar to what previous studies reported, but primarily in younger
      adults with at least 12 years of formal education. In this Brazilian sample, the
      correlation of educational level and BNIS total score was r = .68, p < .001. The
      correlation of age and BNIS total score was r = -.36, p < .001. This is the
      opposite pattern to that observed in previous standardization studies. The strong
      correlation of education with performance in various subtests was observed in all
      age groups (ages ranging from 15 to 85 years). CONCLUSION: This standardization
      study provides guidelines for calculating expected average performance levels on
      the BNIS-PT for Brazilian individuals with varying degrees of age and education.
      Educational level positively correlated with test performance on the BNIS-PT and
      was repeatedly observed to overshadow the effects of age, suggesting its
      important role in the development of higher cerebral functions in multiple
      domains in a Brazilian sample of normally functioning individuals.

PMID- 28511577
TI  - Sonographic assessment of the lower uterine segment during active labor in women
      with or without a uterine scar - a prospective study.
AB  - OBJECTIVES: No study thus far has evaluated the LUS thickness in active labor. In
      this study, we endeavored to assess the LUS during active labor. METHODS: Using
      transabdominal sonography in the mid-sagittal position with a full urinary
      bladder, the thickness of the LUS was measured during active labor phase in women
      with or without a history of a previous cesarean section. RESULTS: A total of 28
      women with a previous cesarean delivery were compared to 29 women without a
      history of uterine surgery. The median LUS was significantly thinner in women
      with a uterine scar both during (4 versus 5 mm, p = .001) and between
      contractions (5 versus 7 mm, p = .011). Paired comparison of LUS thickness
      between and during contractions within each group showed that thinning of LUS
      during contraction was significant for both the previous CS group (p < .001) and
      the control group (p < .001). We found no correlation between LUS thickness and
      chances of successful TOLAC. CONCLUSIONS: In this study, we characterized for the
      first time the LUS during active labor. We found that LUS was significantly
      thinner in women after a previous CS and that the LUS was significantly thinner
      during contraction.

PMID- 28511579
TI  - Does an attention bias to appetitive and aversive words modulate interference
      control in youth with ADHD?
AB  - Interference control refers to the ability to selectively attend to certain
      information while ignoring distracting information. This ability can vary as a
      function of distractor relevance. Distractors that are particularly relevant to
      an individual may attract more attention than less relevant distractors. This is
      referred to as attention bias. Weak interference control and altered reward
      sensitivity are both important features of attention deficit hyperactivity
      disorder (ADHD). However, interference control is typically studied in isolation.
      This study integrates both. Youths (aged 9 to 17 years) with ADHD (n = 37, 25
      boys) and typically-developing controls (n = 38, 20 boys) completed a Stroop task
      using appetitive words and matched neutral words to assess whether appetitive
      distractors diminished interference control more in youths with ADHD than
      controls. In order to test for specificity, aversive words were also included. As
      expected, appetitive words disrupted interference control but this effect was not
      stronger for youths with ADHD than the controls. Aversive words, on the other
      hand, facilitated interference control. Dimensional analyses revealed that this
      facilitation effect increased substantially as a function of ADHD symptom
      severity. Possible mechanisms for this effect include up-regulation of
      interference control as a function of induced negative mood, or as a function of
      increased effort. In conclusion, appetitive words do not lead to worse
      interference control in youths with ADHD compared with controls. Interference
      control was modulated in a valence-specific manner, concurrent with mood-induced
      effects on cognitive control.

PMID- 28511578
TI  - Retinal atrophy in relation to visual functioning and vision-related quality of
      life in patients with multiple sclerosis.
AB  - BACKGROUND: Inner retinal layer atrophy in patients with multiple sclerosis (MS)
      has been validated as a structural imaging biomarker for neurodegeneration.
      OBJECTIVE: To determine how retinal layer thickness relates to high-contrast
      visual acuity (HCVA), low-contrast visual acuity (LCVA) and vision-related
      quality of life (QoL) and to investigate the effect of previous episodes on MS
      associated optic neuritis (MSON). METHODS: Spectral-domain optical coherence
      tomography (SD-OCT) was performed in 267 patients with MS. Images were segmented
      for the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion
      cell inner plexiform layer (GCIPL). Ophthalmological evaluations included history
      of MSON, HCVA, LCVA, and vision-related QoL. RESULTS: Independent of MSON, HCVA
      and LCVA were significantly associated with pRNFL and GCIPL thicknesses. Vision
      related QoL was positively associated with pRNFL (beta = 0.92, p = 0.06) and
      GCIPL (beta = 0.93, p = 0.02) thicknesses. These associations were independent of
      MSON. Not only binocular but also monocular atrophy of the inner retinal layers
      was associated with lower vision-related QoL. CONCLUSION: This study showed that
      retinal atrophy has a significant impact on visual functioning in patients with
      MS. OCT may therefore provide useful insight to patients with visual dysfunction,
      and our findings support including OCT and vision-related QoL measures into optic
      neuritis treatment trials.

PMID- 28511580
TI  - Deleterious Effects From Occupational Exposure to Ethylene Thiourea in Pregnant
      Women.
AB  - Human exposure to endocrine disrupting chemicals (EDCs) has become common as a
      result of widespread application of these chemicals to the food supply,
      environmental contamination, and occupational exposures (Caserta et al., 2011).
      However, relatively little is known about the effects of EDCs such as ethylene
      thiourea (ETU) in developing fetuses and the lasting implications of this
      disruption on human development from birth through adulthood. Of highest concern
      are chronic, low-dose exposures among industrial and agricultural workers.
      Current knowledge regarding the significance of endocrine thyroid signaling on
      normal human development raises serious concerns about the possible deleterious
      effects of EDCs in the developing fetus, children, and mature adults.
      Occupational health nurses are critical in identifying women and families at
      increased risk of ETU exposure and mitigating early exposures in pregnancy.

PMID- 28511581
TI  - The RANZCP guidelines for Schizophrenia: Why is our practice so far short of our
      recommendations, and what can we do about it?
AB  - The new RANZCP guidelines for the treatment of schizophrenia and related
      disorders highlights what we know works. In this paper, we examine why patients
      so often fail to benefit from this knowledge and why clinical practice falls so
      far short of the recommended standard. Instead of the continuous improvement that
      we expect of health care in general, in psychiatry we face an accelerating
      decline in systems of care. There has been a sustained underinvestment in public
      mental health care and a shared failure by State and Federal governments to
      construct and commit to a governance and funding model that can deliver the
      standard of care that is available in other major non-communicable diseases, and
      which we know is equally possible for severe mental illness. This paper sets out
      some of the reasons for the poor quality of care received by many people with
      schizophrenia and related disorders in Australia, and describes ways that care
      could be improved. In particular, we recommend an explicit statement of what
      constitutes an adequate standard of care, for people at all stages of these
      illnesses. This would help provide transparency about whether the care provided
      by mental health services achieves these benchmarks, and enable publication of
      results comparing the performance of different states and regional services.
      Patients and families, as well as professional, consumer and carer organizations
      would then be able to see clearly where the deficits are and demand resources and
      care that match the recommendations.

PMID- 28511582
TI  - Evaluation of an Unfractionated Heparin Pharmacy Dosing Protocol for the
      Treatment of Venous Thromboembolism in Nonobese, Obese, and Severely Obese
      Patients.
AB  - BACKGROUND: Despite large interpatient variability in dose response, heparin is
      utilized for treatment of venous thromboembolism (VTE). Current data on the
      optimal heparin dosing in obese patients are conflicting. OBJECTIVE: The
      objective was to evaluate the time and dose required to achieve a therapeutic
      activated partial thromboplastin time (aPTT) in nonobese, obese, and severely
      obese patients using a pharmacist-directed heparin dosing protocol. METHODS: This
      was a retrospective cohort study in a single-center community hospital inpatient
      setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to
      July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese
      (BMI < 30 kg/m2), obese (BMI = 30-39.9 kg/m2), and severely obese (BMI >= 40
      kg/m2). Data on height, weight, initial bolus dose, initial infusion rate, time
      to therapeutic aPTT, and therapeutic infusion rate were collected. Dosing body
      weight (DBW) was utilized for patients 20% over their ideal body weight (IBW).
      The primary outcome was time to therapeutic aPTT. RESULTS: Analysis included 298
      patients. Median times to therapeutic aPTT (hours:minutes) in the nonobese,
      obese, and severely obese were 15:00 (interquartile range [IQR] = 8:05-23:21),
      15:40 (IQR = 9:22-25:10), and 15:22 (IQR = 7.54-23:40), respectively ( P =
      0.506). There was no difference in bleeding among the nonobese (14%), obese
      (13.9%), or severely obese groups (7.9%; P = 0.453). No adverse thrombotic events
      occurred during hospitalization. CONCLUSION: Using a DBW for heparin dosing in
      patients 20% over their IBW resulted in similar times to therapeutic aPTT and
      adverse events in the nonobese, obese, and severely obese.

PMID- 28511583
TI  - Deciphering the crucial residues involved in heterodimerization of Bak peptide
      and anti-apoptotic proteins for apoptosis.
AB  - B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of
      apoptosis, functioning via mitochondrial outer membrane permeabilization. The
      family members are involved in several stages of apoptosis regulation. The
      overexpression of the anti-apoptotic proteins leads to several cancer
      pathological conditions. This overexpression is modulated or inhibited by
      heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the
      hydrophobic groove present at the surface of anti-apoptotic proteins.
      Additionally, the heterodimerization displayed differences in binding affinity
      profile among the pro-apoptotic peptides binding to anti-apoptotic proteins. In
      light of discovering the novel peptide/drug molecules that contain the potential
      to inhibit specific anti-apoptotic protein, it is necessary to understand the
      molecular basis of recognition between the protein and its binding partner
      (peptide or ligand) along with its binding energies. Therefore, the present work
      focused on deciphering the molecular basis of recognition between pro-apoptotic
      Bak peptide binding to different anti-apoptotic (Bcl-xL, Bfl-1, Bcl-W, Mcl-1, and
      Bcl-2) proteins using advanced Molecular Dynamics (MD) approach such as Molecular
      Mechanics-Generalized Born Solvent Accessible. The results from our investigation
      revealed that the predicted binding free energies showed excellent correlation
      with the experimental values (r2 = .95). The electrostatic (DeltaGele)
      contributions are the major component that drives the interaction between Bak
      peptides and different anti-apoptotic peptides. Additionally, van der Waals
      (DeltaGvdw) energies also play an indispensible role in determining the binding
      free energy. Furthermore, the decomposition analysis highlighted the
      comprehensive information about the energy contributions of hotspot residues
      involved in stabilizing the interaction between Bak peptide and different anti
      apoptotic proteins.

PMID- 28511584
TI  - A Pilot Intervention Designed to Address Behavioral Factors That Place
      Overweight/Obese Young Children at Risk for Later-Life Obesity.
AB  - The purpose of this pilot randomized controlled trial (RCT) was to intervene with
      parents of overweight/obese 4- to 8-year-old children to improve child
      internalizing and externalizing behaviors. Parent-child dyads ( N = 60) were
      randomly assigned to treatment or comparison conditions. Parents attended four
      intervention sessions at their child's primary health care office over 3 months.
      Child behaviors were assessed at 0, 3, 6, and 12 months post intervention.
      Parental beliefs in their skills/abilities increased in the experimental group
      parents, but there was no statistical difference between groups at any time.
      Child externalizing behaviors significantly decreased from baseline to
      postintervention for both groups ( F = 3.26, p = .020). Post hoc model testing
      suggests that this change was more pronounced in the intervention group ( F =
      0.56, p = .692). Child somatic symptoms significantly decreased over time ( F =
      4.55, p = .004), and there were group differences in child depressive behaviors (
      F = 6.19, p = .020). These findings suggest that a parent-focused intervention
      program demonstrated positive preliminary effects on children's behaviors.

PMID- 28511585
TI  - Three-Phase Adaptive Radiation Therapy for Patients With Nasopharyngeal Carcinoma
      Undergoing Intensity-Modulated Radiation Therapy: Dosimetric Analysis.
AB  - Patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation
      therapy may experience significant anatomic changes throughout the entire
      treatment course, and adaptive radiation therapy may be necessary to maintain
      optimal dose delivered both to the targets and to the critical structures. The
      timing of adaptive radiation therapy, however, is largely unknown. This study was
      to evaluate the dosimetric benefits of a 3-phase adaptive radiation therapy
      technique for nasopharyngeal carcinoma. Twenty patients with nasopharyngeal
      carcinoma treated with intensity-modulated radiation therapy were recruited
      prospectively. After fractions 5 and 15, each patient had repeat computed
      tomography scans, and adaptive replans with recontouring the targets and organs
      at risk on the new computed tomography images were generated and used for
      subsequent treatment (replan 1 and replan 2). Two hybrid intensity-modulated
      radiation therapy plans (plan 1 and plan 2) were generated by superimposing the
      initial plan (plan 0) to each repeated new computed tomography image, reflecting
      the actual dose delivered to the targets and organs at risk if no changes were
      made to the original plan. Dosimetric comparisons were made between the adaptive
      replans (adaptive radiation therapy plans: plan 0 + replan 1 + replan 2) and
      their corresponding nonadaptive radiation therapy plans (plan 0 + plan 1 + plan
      2). Comparing with the nonadaptive radiation therapy plans, the adaptive
      radiation therapy plans resulted in a significant improvement in conformity index
      for planning target volumes for primary disease, involved lymph node, high-risk
      clinical target volume, and low-risk clinical target volume (PTVnx, PTVnd, PTV1,
      and PTV2, respectively). Median V95 for PTVnx; D95, D99, V100, V95, and V93 for
      PTVnd; D99 and V100 for PTV1; and D95, D99, V100, V95, and V93 for PTV2 were
      increased significantly. There were significant dose-volume reductions, including
      maximum doses to the brainstem and temporal lobes, mean doses to the glottis, V50
      for the supraglottis, Dmean and V30 for the left parotid, median dose to the
      right optic nerve, and V55 for the skin. The 3-phase adaptive intensity-modulated
      radiation therapy for patients with nasopharyngeal carcinoma results in
      improvements in target coverage and conformity index and decreased doses to some
      organs at risk.

PMID- 28511586
TI  - Bioprocess optimization of PHB homopolymer and copolymer P3 (HB-co-HV) by
      Acinetobacter junii BP25 utilizing rice mill effluent as sustainable substrate.
AB  - The potential use of parboiled rice mill effluent as a cheap substrate for the
      production of homopolymer and copolymer of Polyhydroxyalkanoates (PHAs) by
      Acinetobacter junii BP 25 was investigated for the first time. Process
      optimization by one factor at a time led to homopolymer polyhydroxybutyrate (PHB)
      production of 2.64 +/- 0.18 g/l with 94.28% PHB content using a two-stage batch
      cultivation mode. BP 25 furthermore produced polyhydroxybutyrate-co
      hydroxyvalerate (P3 (HB-co-HV)), with the addition of valeric acid as an additive
      to the substrate, yielding (2.56 +/- 0.12 g/l dry biomass, 2.20 +/- 0.15 g/l PHA)
      a copolymer content of 85.93%. Thus, rice mill effluent can be an effective and
      relatively low-cost alternative for the production of PHA, replacing the pure
      substrates.

PMID- 28511588
TI  - An evening milk drink can affect word recall in Indonesian children with
      decreased sleep efficiency: A randomized controlled trial.
AB  - STUDY OBJECTIVES: Sleep is important for memory consolidation in children. This
      study intended to find out whether an evening milk-based drink could influence
      sleep efficiency and memory recall in a group of Indonesian children (5-6 years
      old) with sleep deprivation. METHODS: Children were randomly allocated to one of
      three interventions: Reference product, satiety-stimulating product, and a
      relaxing product. The intervention lasted for 6 weeks and children consumed two
      servings per day of each 200 ml, the serving in the morning being the same for
      all children. All measurements took place at baseline and at the end of the
      intervention. Sleep parameters were studied using actigraphy and a sleep diary
      during three consecutive days. Memory consolidation was tested using a 20 word
      pair list, which was memorized the evening before being recalled the next morning
      at home-base. Anthropometry was measured using standard equipment. RESULTS: The
      Satiety group showed a significant decrease in word recall, and a significant
      increase in nocturnal awakenings that was inversely associated with sleep
      efficiency at the end of the intervention. Sleep efficiency did not differ
      between the three groups being 75.5 +/- 8.6% and 75.7 +/- 6.3% at baseline and
      end of the intervention, respectively. Despite the lower energy intake in the
      Standard (reference) group, this condition showed the highest increase in weight.
      DISCUSSION: Evening growing-up milks can affect memory recall, sleep
      characteristics, and growth. However, to correct sleep efficiency and sleep
      duration, improvement of parental behavior may be the most important factor with
      nutrition providing a supplementary effect.

PMID- 28511590
TI  - Temperature Rise in Kirschner Wires Inserted Using Two Drilling Methods: Forward
      and Oscillation.
AB  - BACKGROUND: Kirschner wires (K-wires) are commonly used in orthopedic surgery.
      However, the loosening of the pins can lead to delayed or improper healing or
      infection. Wire loosening can occur by thermal necrosis that occurs due to heat
      produced during wire insertion. Although the parameters that affect temperature
      rise in cortical bone during wire insertion and drilling have been studied, the
      effect of drilling mode (oscillation versus forward) is unknown. The purpose of
      this study was to compare the temperature changes occurring in cortical bone
      during wire insertions by oscillating and forward drills. Our hypothesis is that
      oscillation drilling would produce less heat compared with forward drilling in K
      wire insertion with 2 commonly used wire diameters. METHODS: We drilled K-wires
      in a pig metacarpal model and measured the temperature rise between forward and
      oscillation drilling modes using diamond-tipped 0.062- and 0.045-inch-diameter K
      wires. There were 20 holes drilled for each group (n = 20). RESULTS: The average
      temperature rise using the 0.062-inch K-wire under forward and oscillation
      insertion was 14.0 +/- 5.5 degrees C and 8.8 +/- 2.6 degrees C, respectively. For
      the 0.045-inch K-wire, under forward and oscillation insertion, the average
      temperature rise was 11.4 +/- 2.6 degrees C and 7.1 +/- 1.9 degrees C,
      respectively. The effects of the drilling mode and wire diameter on temperature
      rise were significant ( P < .05). CONCLUSIONS: In conclusion, the oscillation of
      K-wires during insertion causes a lower temperature rise when compared with
      forward drilling.

PMID- 28511589
TI  - A semi-automatic method for the extraction of the portal venous input function in
      quantitative dynamic contrast-enhanced CT of the liver.
AB  - OBJECTIVE: To aid the extraction of the portal venous input function (PVIF) from
      axial dynamic contrast-enhanced CT images of the liver, eliminating the need for
      full manual outlining of the vessel across time points. METHODS: A cohort of 20
      patients undergoing perfusion CT imaging of the liver was examined. Dynamic
      images of the liver were reformatted into contiguous thin slices. A region of
      interest was defined within a transverse section of the portal vein on a single
      contrast-enhanced image. This region of interest was then computationally
      projected across all thin slices for all time points to yield a semi-automated
      PVIF curve. This was compared against the "gold-standard" PVIF curve obtained by
      conventional manual outlining. RESULTS: Bland-Altman plots of curve
      characteristics indicated no substantial difference between automated and manual
      PVIF curves [concordance correlation coefficient in the range (0.66, 0.98)]. No
      substantial differences were shown by Bland-Altman plots of derived
      pharmacokinetic parameters when a suitable kinetic model was applied in each case
      [concordance correlation coefficient in range (0.92, 0.95)]. CONCLUSION: This
      semi-automated method of extracting the PVIF performed equivalently to a "gold
      standard" manual method for assessing liver function. Advances in knowledge: This
      technique provides a quick, simple and effective solution to the problems
      incurred by respiration motion and partial volume factors in the determination of
      the PVIF in liver dynamic contrast-enhanced CT.

PMID- 28511591
TI  - Psychometric evaluation of the Signs of Depression Scale with a revised scoring
      mechanism in stroke patients with communicative impairment.
AB  - OBJECTIVES: To investigate (1) the diagnostic value of the Signs of Depression
      Scale (SODS) in a Likert scale format and (2) whether the Likert scale improves
      the diagnostic value compared with the original dichotomous scale. DESIGN: Cross
      sectional multicentre study. SETTING: One general and one university hospital in
      the Netherlands. SUBJECTS: A total of 116 consecutive hospitalized stroke
      patients, of whom 53 were patients with communicative impairment. MAIN MEASURES:
      Depression was diagnosed with the Composite International Diagnostic Interview
      (CIDI) administered to the patients' relatives. The Barthel Index (BI) was used
      as an external validator. RESULTS: The correlation between the CIDI and the SODS
      Likert or the SODS was small ( rb = 0.18), and the correlation between the
      Barthel Index and the SODS-Likert ( rs = -0.30) or the SODS ( rs = -0.33) was
      moderate. For both instruments, the discriminatory power for diagnosing
      depression when compared with the CIDI was best at a cut-off score of ?2. The
      internal consistency of the SODS-Likert was acceptable (alpha = 0.69) and
      slightly higher than that of the SODS (alpha = 0.57). The inter-rater reliability
      of the SODS-Likert and the SODS was acceptable (intraclass correlation
      coefficient (ICC) 0.66 and ICC 0.80, respectively). The clinical utility was
      rated good. CONCLUSION: The diagnostic value of the SODS did not improve using a
      Likert scale format. However, the diagnostic value of the original dichotomous
      SODS is reasonable for the initial mood assessment of stroke patients with
      communicative impairment.

PMID- 28511592
TI  - Cytotoxicity, mutagenicity, and antimutagenicity of the gentisic acid on HTC
      cells.
AB  - Gentisic acid (GA) exhibits antioxidant, anti-inflammatory, and antibiotic
      activities. This substance can be found in citrus fruits, grapes, olive oil, and
      peas. Considering that there are few studies in the literature on the toxicity of
      GA, the present work aimed to investigate its cytotoxic, mutagenic, and
      antimutagenic activities on HTC cells. GA was diluted in culture medium at the
      final concentration of 0.08, 0.16, 0.8, 1.6, and 8 MUg/mL. The cytotoxicity was
      determined by the MTT assay and Trypan Blue exclusion method, with methyl
      methanesulfonate and doxorubicin as positive controls, respectively. The
      cytokinesis-block micronucleus assay determined the mutagenic/antimutagenic
      activity with benzo[a]pyrene as positive control. Negative control received
      culture medium only. GA (0.08-8 MUg/mL) was not cytotoxic to HTC cells by the MTT
      assay nor the Trypan Blue exclusion method as no statistical difference was
      observed when compared to the control. Concentration of 0.08 and 0.8 MUg/mL
      showed no mutagenic or clastogenic effects, as no significant micronuclei
      inductions were observed, different from 8 MUg/mL, that was mutagenic.
      Furthermore, none of the concentrations presented an antiproliferative activity.
      The antimutagenic activity of GA (0.08 MUg/mL) was observed at the simultaneous
      treatment, as it reduced the frequency of micronuclei by 76% (24 h) and 79% (48
      h). Although pre- and post-treatments were not statistically different from the
      mutagen, they reduced the induced-damage by 11% and 21%, respectively. The
      present study indicated the absence of cytotoxicity and antiproliferative
      activities of GA, in addition to their antimutagenic/protective effects that may
      contribute to human health.

PMID- 28511593
TI  - Convergence Insufficiency Identifies Athletes at Risk of Prolonged Recovery From
      Sport-Related Concussion.
AB  - BACKGROUND: Sensitive and specific screening methods are needed to identify
      athletes at risk of prolonged recovery after sport-related concussion (SRC).
      Convergence insufficiency (CI) is a common finding in concussed athletes.
      PURPOSE: To assess the relationship between CI and recovery after SRC at the
      initial office visit. STUDY DESIGN: Case-control study; Level of evidence, 3.
      METHODS: In this retrospective cohort study, 270 athletes (147 male, 123 female),
      mean +/- SD age 14.7 +/- 2.0 years (range, 10-21 years), with the diagnosis of
      SRC who presented for initial office visit between January 2014 and January 2016
      were evaluated for near point of convergence (NPC). The athletes were categorized
      into 2 groups: normal near point of convergence (NPC <=6 cm), and convergence
      insufficiency (NPC >6 cm). These athletes were then followed to determine
      recovery time. RESULTS: Athletes presented for initial office visit at a mean of
      5.2 +/- 4.2 days (range, 1-21 days) after SRC. Half of the athletes had CI after
      SRC (50.4%; n = 136). Athletes with CI (NPC 12.3 +/- 4.7 cm) took significantly
      longer to recover after SRC, requiring 51.6 +/- 53.9 days, compared with athletes
      with normal NPC (4.1 +/- 1.3 cm), who required 19.2 +/- 14.7 days ( P < .001).
      After controlling for potential confounding variables, CI significantly increased
      the odds of prolonged recovery (>=28 days from injury) by 12.3-fold ( P < .001;
      95% confidence interval, 6.6-23.0). CI screening correctly classified 75.2% of
      our sample with 84.2% sensitivity and 70.0% specificity. The positive predictive
      value for CI and prolonged recovery was 62.5%, and the negative predictive value
      was 88.1%. CONCLUSION: CI at the initial office visit identified athletes at
      increased risk of prolonged recovery after SCR. Clinicians should consider
      measuring NPC in concussed athletes as a quick and inexpensive prognostic
      screening method.

PMID- 28511594
TI  - Fixation Strength in Full and Limited Fixation of Osteoporotic Distal Radius
      Fractures.
AB  - BACKGROUND: The purpose of this investigation is to determine whether
      osteoporotic intra-articular distal radius fractures surgically treated by
      filling all 7 distal screws of a volar plate will have a higher load to failure
      than those treated by filling only 4 distal screws. METHODS: Ten matched pairs of
      fresh frozen cadaveric forearms were randomized within each pair to be treated by
      using either all 7 of the distal holes of a volar plate or only 4 distal screws.
      The distal radius fixation was performed with unicortical screws going to but not
      through the dorsal cortex, and the most distal screws were placed within 4 mm of
      the joint surface. An AO C2 type fracture was then created. All specimens were
      tested cyclically, with an axial load of 60 N, at 3 Hz for 1000 cycles to
      simulate early postoperative motion. All specimens were subsequently tested to
      mechanical failure. RESULTS: There were no failures in either group during cyclic
      testing. There was no difference detected between groups for mean stiffness,
      yield load, peak load, or load to clinical failure. In both groups, the yield
      load, peak load, and load to clinical failure were higher than the 60- to 100-N
      forces encountered during postoperative rehabilitation. CONCLUSIONS: There was no
      difference detected between osteoporotic intra-articular distal radius fractures
      treated by utilizing all 7 of the distal screws of a volar plate compared with
      those treated with only 4 distal screws.

PMID- 28511595
TI  - Presence and Predictive Value of Obsessive-Compulsive Symptoms in Anxiety and
      Depressive Disorders.
AB  - OBJECTIVE: Obsessive-compulsive symptoms (OCS) co-occur frequently with anxiety
      and depressive disorders, but the nature of their relationship and their impact
      on severity of anxiety and depressive disorders is poorly understood. In a large
      sample of patients with anxiety and depressive disorders, we assessed the
      frequency of OCS, defined as a Young Adult Self-Report Scale-obsessive-compulsive
      symptoms score >7. The associations between OCS and severity of anxiety and/or
      depressive disorders were examined, and it was investigated whether OCS predict
      onset, relapse, and persistence of anxiety and depressive disorders. METHODS:
      Data were obtained from the third (at 2-year follow-up) and fourth wave (at 4
      year follow-up) of data collection in the Netherlands Study of Anxiety and
      Depression cohort, including 469 healthy controls, 909 participants with a
      remitted disorder, and 747 participants with a current anxiety and/or depressive
      disorder. RESULTS: OCS were present in 23.6% of the total sample, most notably in
      those with current combined anxiety and depressive disorders. In patients with a
      current disorder, OCS were associated with severity of this disorder. Moreover,
      OCS predicted (1) first onset of anxiety and/or depressive disorders in healthy
      controls (odds ratio [OR], 5.79; 95% confidence interval [CI], 1.15 to 29.14),
      (2) relapse in those with remitted anxiety and/or depressive disorders (OR, 2.31;
      95% CI, 1.55 to 3.46), and (3) persistence in patients with the combination of
      current anxiety and depressive disorders (OR, 4.42; 95% CI, 2.54 to 7.70) within
      the 2-year follow-up period Conclusions: OCS are closely related to both the
      presence and severity of anxiety and depressive disorders and affect their course
      trajectories. Hence, OCS might be regarded as a course specifier signaling
      unfavorable outcomes. This specifier may be useful in clinical care to adapt and
      intensify treatment in individual patients.

PMID- 28511597
TI  - Understanding sleep-wake mechanisms and drug discovery.
AB  - INTRODUCTION: Although not discernible at first glance, sleep is a highly active
      and regulated brain state. Although we spend practically one third of our
      lifetimes in this stage, its importance is often taken for granted. Sleep loss
      can lead to disease, error and economic loss. Our understanding of how sleep is
      achieved has greatly advanced in recent years, and with that, the management of
      sleep disorders has improved. There is still room for improvement and recently
      many new compounds have reached clinical trials with a few being approved for
      commercial use. Areas covered: In this review, the authors make the case of sleep
      disorders as a matter of public health. The mechanisms of sleep transition are
      discussed emphasizing the wake and sleep promoting interaction of different brain
      regions. Finally, advances in pharmacotherapy are examined in the context of
      chronic insomnia and narcolepsy. Expert opinion: The orexinergic system is an
      example of a breakthrough in sleep medicine that has catalyzed drug development.
      Nevertheless, sleep is a topic still with many unanswered questions. That being
      said, the melanin-concentrating hormone system is becoming increasingly relevant
      and we speculate it will be the next target of sleep medication.

PMID- 28511598
TI  - Silexan in anxiety disorders: Clinical data and pharmacological background.
AB  - OBJECTIVES: Silexan is a lavender oil preparation available in 80-mg capsules.
      Here we review clinical trials investigating its anxiolytic efficacy, safety and
      tolerability in humans, as well as preclinical investigations supporting this
      therapeutic use. METHODS: Besides three selected publications reporting
      preclinical investigations, seven clinical trials are included, of which five had
      a treatment duration of 6 or 10 weeks. Primary outcome measure was the HAM-A
      total score reduction, while single items were assessed with regard to effects on
      concomitant depressive symptoms and on quality of sleep. RESULTS: In patients
      with subthreshold (subsyndromal) anxiety or generalised anxiety disorder (GAD),
      an anxiolytic effect of Silexan was evident after 2 weeks. HAM-A total score
      reductions between baseline and end of treatment were significantly superior to
      placebo in patients with subthreshold anxiety and comparable with those achieved
      under lorazepam or paroxetine in patients with GAD. In addition, Silexan had
      beneficial effects on typical concomitant symptoms of anxiety disorders, such as
      impaired sleep, somatic complaints, co-morbid depression or decreased quality of
      life. Except for mild gastrointestinal symptoms, Silexan did not induce any
      adverse effects and did not cause drug interactions, sedation or withdrawal
      symptoms at daily doses of 80 or 160 mg. CONCLUSIONS: Silexan is a safe and
      effective treatment in anxiety disorders.

PMID- 28511599
TI  - Teething.
AB  - Misconceptions about the teething process has led to high infant morbidity and
      mortality, which was recently experienced in Nigeria due to consumption of an
      adulterated drug used in the prevention and treatment of teething-related
      illnesses in infants. It is however, unknown if these misconceptions still
      persist in a rural town in Nigeria despite oral health awareness campaigns
      targeted at this. The aim of this study is to assess the beliefs and practices of
      residents in Igbo Ora, a rural township in Nigeria, regarding the teething
      process. A descriptive cross-sectional study was conducted among 393 adults in
      Igbo Ora using a 33-item, semistructured questionnaire. Symptoms such as diarrhea
      (80.7%), fever (69.2%), and boils (64.4%) were still considered as a must to
      accompany teething. Teething powder, teething syrup, and traditional concoctions
      were commonly recommended by (42.0%), (31.6%), and (48.1%) of the respondents,
      respectively, to treat and prevent teething symptoms. This study revealed that
      misconceptions about teething are still highly prevalent among the populace in
      Igbo Ora, and a structured oral health education intervention at the community
      level is urgently needed.

PMID- 28511600
TI  - Knowledge Attitude and Practices Toward Lassa Fever Control and Prevention Among
      Residents of Ile-Ife, Southwest Nigeria.
AB  - Lassa fever had been reported as a cause of death especially in endemic parts of
      Nigeria. This study assessed the knowledge, attitude, and practices toward Lassa
      fever control and prevention among residents of Ile-Ife, southwest Nigeria.
      Descriptive cross-sectional study was conducted among consenting randomly
      selected adults using an interviewer administered questionnaire. Data were
      analyzed using descriptive and inferential statistics. A total of 400
      questionnaires with completed data were analyzed (response rate 96%). Majority,
      207 (51.8%), were males while 193 (48.2%) were females. Most, 234 (58.5%), had
      tertiary education while 148 (37%) had secondary education. Fifty-nine percent
      had heard of Lassa fever with radio as their major source of information. About
      76% had inadequate knowledge, 54% had negative attitude while 51% had poor
      practice toward Lassa fever. Determinants of knowledge of Lassa fever include
      having higher education (Adjusted Odd Ratio (AOR) = 11.49, 95% CI [3.10, 42.69],
      p = .0001), being in civil service (AOR = 0.22, 95% CI [0.09, 0.51], p = .01),
      and earning higher income (AOR = 4.23, 95% CI [2.61, 6.84], p = .0001). In
      conclusion, the knowledge, attitude, as well as preventive practices to Lassa
      fever were poor. It is necessary to increase public education and improve
      hygienic practices.

PMID- 28511601
TI  - Satisfaction of Patients Attending Public HIV or AIDS Care and Treatment Centers
      in Kinondoni District, Tanzania.
AB  - Satisfaction of care and treatment among HIV patients is one of the important
      elements for adherence. This study aimed to determine levels of satisfaction and
      associated factors among HIV-infected patients attending public care and
      treatment centers (CTCs) in Tanzania. The study was cross-sectional using face-to
      face interviews. Satisfaction was measured using a total of 30 questions from a
      domain of six area of CTC service delivery. To assess independent predictors of
      levels of satisfaction, we used multilevel ordinal logistic regression analysis.
      We enrolled 434 study participants. Of these, 5% reported low satisfaction, 25%
      medium satisfaction, and 70% reported high satisfaction. The CTC environment was
      rated low by 56% of the patients. Predictors of levels of satisfaction were age
      of patient and health facility level. Low levels of satisfaction with CTC
      environment and laboratory services underscore the need for improvement of these
      areas.

PMID- 28511602
TI  - Evaluation of Student Handwashing Practices During a School-Based Hygiene Program
      in Rural Western Kenya, 2007.
AB  - Unsafe drinking water and inadequate handwashing facilities in primary schools
      increase the risk of absenteeism due to diarrhea and respiratory infections. To
      mitigate these risks, we provided 28 schools in rural Western Kenya with
      handwashing and drinking water stations (containers with lids and taps on metal
      stands), bleach for water treatment, soap for handwashing, and educational
      materials. We observed the use of the water stations and assessed teachers'
      attitudes toward the intervention. Of 151 total handwashing stations, 69 (59%)
      were observed to have soap and water and treated drinking water 4 months after
      implementation; observations of pupils showed an increase in handwashing behavior
      in water stations located < 10 m, as compared with those >10 m, from latrines ( p
      < .02). In focus groups, teachers reported improved cleanliness and decreased
      illness in pupils. Teacher training and installation of water stations resulted
      in observed improvements in pupils' hygiene, particularly when water stations
      were located <10 m from latrines.

PMID- 28511603
TI  - Clinical Experience With Perampanel for Refractory Pediatric Epilepsy in One
      Canadian Center.
AB  - Perampanel (PER) is a new antiseizure medication that inhibits the alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors.
      It is important for physicians to be aware of the efficacy and tolerability of
      new drugs in the postmarketing phase. We performed a retrospective review of our
      experience with perampanel at BC Children's Hospital. Twenty-four pediatric
      patients prescribed perampanel from 2014 to 2016 were identified. Fifteen (63%)
      discontinued perampanel, and 10 (42%) had greater than 50% reduction in seizures.
      Twelve (50%) had behavioral and 8 (33%) had nonbehavioral adverse events. One
      third experienced serious adverse events. One patient experienced oculogyric
      crisis, which is not previously reported with perampanel. Adverse events were not
      dose related and were reversible. Possible risk factors for behavioral adverse
      events include a history of behavioral problems with other antiseizure
      medications and preexisting behavioral comorbidities. It is important to counsel
      patients about the potential for serious adverse events, particularly behavioral,
      when prescribing perampanel.

PMID- 28511604
TI  - Duplicated or Hybridized Peptide Functional Domains Promote Oral Homeostasis.
AB  - Proteins that have existed for millions of years frequently contain repeats of
      functional domains within their primary structure, thereby improving their
      functional capacity. In the evolutionary young statherin protein contained within
      the in vivo-acquired enamel pellicle (AEP), we identified a single functional
      domain (DR9) located within the protein N-terminal portion that exhibits a higher
      affinity for hydroxyapatite and more efficient protection against enamel
      demineralization compared to other native statherin peptides. Thus, we tested the
      hypothesis that multiplication of functional domains of naturally occurring
      pellicle peptides amplifies protection against enamel demineralization. In
      addition, a specific amino acid sequence from histatin 3 (RR-14) was introduced
      to the hybrid peptides for further testing. Enamel specimens were sectioned to
      150-um thickness and randomly grouped as follows: DR9, DR9-DR9, DR9-RR14,
      statherin, histatin 1, or distilled water (control). After submersion for 2 h at
      37 degrees C, the specimens were placed in 2 mL demineralization solution for 12
      d at 37 degrees C. Upon sample removal, the remaining solution was subjected to
      colorimetric assays to determine the amount of calcium and phosphate released
      from each specimen. DR9-DR9 amplified protection against enamel demineralization
      when compared to single DR9 or statherin. Notably, the hybrid peptide DR9-RR14
      demonstrated relatively strong protection when the antimicrobial property of
      these peptides was tested against Candida albicans and Streptococcus mutans. DR9
      RR14 was able to maintain 50% of the antifungal activity compared with RR14 for
      C. albicans and similar values of S. mutans killing activity. This study has
      pioneered the functional exploration of the natural peptide constituents of the
      AEP and their evolution-inspired engineered peptides. The knowledge obtained here
      may provide a basis for the development of stable (proteinase-resistant)
      synthetic peptides for therapeutic use against dental caries, dental erosion,
      and/or oral candidiasis.

PMID- 28511607
TI  - Increasing the use of psychiatric advance directives.

PMID- 28511605
TI  - 'It was all intertwined': Illness representations and self-management in patients
      with cancer and anxiety/depression.
AB  - OBJECTIVE: Cancer and anxiety/depression frequently co-occur, leading to poorer
      outcomes for these illnesses. However, the majority of existing research
      investigates how participants view single illnesses alone. This study aimed to
      explore the content of individuals' multimorbid representations and how these
      relate to their coping behaviours and self-management strategies for cancer and
      anxiety/depression. DESIGN: A semi-structured qualitative research design with
      theoretical thematic analysis. MAIN OUTCOME MEASURES: Multimorbid illness
      representations, coping behaviours, and self-management strategies. RESULTS: In
      interviews with 21 participants multimorbid representations varied, three
      participants viewed cancer and anxiety/depression as unrelated, five participants
      were uncertain about the relationship between cancer and anxiety/depression, and
      the majority of participants perceived cancer and anxiety/depression as related.
      This third group of participants often described relationships as causal, with
      representations having both positive and negative influences on coping behaviours
      and self-management strategies. Representations were shown to change over the
      course of the cancer experience, with fear of cancer recurrence and the influence
      of participants' most challenging illness also discussed. CONCLUSIONS: People
      hold multimorbid illness representations that can influence self-management. An
      awareness of these representations by researchers, health professionals, and
      patients is important for the creation of future interventions that aim to
      improve and maintain patient wellbeing.

PMID- 28511609
TI  - Why the history of nursing ethics matters.
AB  - Modern American nursing has an extensive ethical heritage literature that extends
      from the 1870s to 1965 when the American Nurses Association issued a policy paper
      that called for moving nursing education out of hospital diploma programs and
      into colleges and universities. One consequence of this move was the dispersion
      of nursing libraries and the loss of nursing ethics textbooks, as they were
      largely not brought over into the college libraries. In addition to approximately
      100 nursing ethics textbooks, the nursing ethics heritage literature also
      includes hundreds of journal articles that are often made less accessible in
      modern databases that concentrate on the past 20 or 30 years. A second
      consequence of nursing's movement into colleges and universities is that ethics
      was no longer taught by nursing faculty, but becomes separated and placed as a
      discrete ethics (later bioethics) course in departments of philosophy or
      theology. These courses were medically identified and rarely incorporated
      authentic nursing content. This shift in nursing education occurs
      contemporaneously with the rise of the field of bioethics. Bioethics is rapidly
      embraced by nursing, and as it develops within nursing, it fails to incorporate
      the rich ethical heritage, history, and literature of nursing prior to the
      development of the field of bioethics. This creates a radical disjunction in
      nursing's ethics; a failure to more adequately explore the moral identity of
      nursing; the development of an ethics with a lack of fit with nursing's ethical
      history, literature, and theory; a neglect of nursing's ideal of service; a
      diminution of the scope and richness of nursing ethics as social ethics; and a
      loss of nursing ethical heritage of social justice activism and education. We
      must reclaim nursing's rich and capacious ethics heritage literature; the history
      of nursing ethics matters profoundly.

PMID- 28511610
TI  - Women without vulvodynia can have a positive 'Q-tip test': a cross sectional
      study.
AB  - BACKGROUND: Vulvodynia is a frequently missed pathology, often confused with
      vaginismus. The Q-tip test (QTT) is fundamental for the diagnosis; however, there
      is lack of data about its performance in asymptomatic women. OBJECTIVE: This
      study intended to evaluate the QTT for painful vestibular spots in asymptomatic
      women. METHODS: Q-tips were gently pressed at different areas of the vulvar
      vestibule to obtain a 0-10 score representing the pain felt. This was performed
      in 267 consecutive patients presenting to the gynecology outpatient clinic for
      reasons other than vulvovaginal complaints. A questionnaire was done to evaluate
      the possibility of unrecognized vulvodynia. RESULTS: Out of the 267 women, 18
      (6.7%) fitted the diagnosis of vulvodynia and were excluded from the analysis. Of
      the remaining 249, 41 (16.5%) had a positive QTT. We could not find differences
      in the sexual activity rate between women with and without a positive QTT. No
      demographic differences could be found between the two groups. Only depression
      was more common in women with a positive QTT [31.7% (13/41) versus 10.8%
      (21/208), p=.001). CONCLUSIONS: Asymptomatic women can have painful vestibular
      spots in the absence of vulvodynia. A positive QTT cannot be considered
      equivalent to vulvodynia, highlighting the need for extensive workup of these
      women before that diagnosis can be assumed.

PMID- 28511611
TI  - Arthroscopic Assisted Resection of Triangular Fibrocartilage Complex Lesions: A
      19-Year Follow-up.
AB  - BACKGROUND: This study assesses long-term functional and subjective outcomes
      following arthroscopic assisted resection of lesions of the triangular
      fibrocartilage complex (TFCC). METHODS: Functional and subjective outcomes were
      assessed based on review of patient charts for patient demographic
      characteristics, comprehensive clinical evaluation, obtained radiographs, and
      patient-reported questionnaires. RESULTS: Fifteen patients, of whom 9 were
      female, and 10 dominant wrists, were included in this study. Median age was 60
      (range, 37-73) years, and median duration of follow-up was 19 (range, 18-21)
      years. Median Mayo Wrist Score was 85 (range, 45-100). Four patients scored
      excellent, 7 good, 3 fair, and 1 poor result according to the Modified Mayo Wrist
      Score. Median Quick Disabilities of the Arm, Shoulder and Arm was 20 (range, 0
      45) and Patient-Rated Wrist and Hand Evaluation was 8 (range, 0-61). Patients
      reported high rate for satisfaction and low rate for pain. All patients presented
      intact stability of the distal radioulnar joint. CONCLUSIONS: This study
      demonstrates persisting satisfactory subjective and functional outcomes for
      patients following arthroscopic assisted resection for lesions of the TFCC at 19
      years of follow-up. Arthroscopically assisted resection of selected TFCC lesions
      seems to be both a safe and efficient procedure.

PMID- 28511612
TI  - NGS analysis on tumor tissue and cfDNA for genotype-directed therapy in
      metastatic NSCLC patients. Between hope and hype?
AB  - INTRODUCTION: The advent of genomic based precision medicine led to the
      implementation of biomarker testing in metastatic non-small cell lung cancer
      (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented
      to routine diagnostic requirements in lung oncology. Areas covered: Two cases of
      patients with metastatic NSCLC for whom NGS analysis performed on both tumor and
      liquid biopsy has not improved the clinical course of their disease are reported.
      These cases illustrate the difficulty of the so-called 'personalized or
      precision' medicine in clinical routine practice for metastatic NSCLC. Expert
      commentary: Discovery and detection of critical cancer-gene alterations better
      indicates targeted therapies that must be administered to improve the care of
      NSCLC patients in the personalized medicine era. There has been much interest in
      the literature and the scientific community for NGS tailored therapies approach
      for patients. However, there may be a gap between this theoretical stratified
      medicine and clinical practice. The advantages and drawbacks of NGS on tumor
      tissue and cell-free DNA for metastatic NSCLC are discussed.

PMID- 28511613
TI  - Antimicrobial activity and molecular docking studies of a novel anthraquinone
      from a marine-derived fungus Aspergillus versicolor.
AB  - A novel anthraquinone, 2-(dimethoxymethyl)-1-hydroxyanthracene-9,10-dione (1),
      together with nine known compounds (2-10), were isolated from the fermentation of
      Aspergillus versicolor derived from deep sea sediment. Their structures were
      established through spectroscopic methods. Compound 1 exhibited strong inhibitory
      activities against MRSA ATCC 43300 and MRSA CGMCC 1.12409 (with MIC values of 3.9
      and 7.8 MUg/mL respectively) and moderate activities against tested strains of
      Vibrio (with MIC values ranging from 15.6 to 62.5 MUg/mL). Compound 1 was
      subjected to molecular docking studies for inhibition of topoisomerase IV and
      AmpC beta-lactamase enzymes indicating its usefulness as antimicrobial agent.

PMID- 28511616
TI  - Bayesian meta-analysis: The role of the between-sample heterogeneity.
AB  - The random effect approach for meta-analysis was motivated by a lack of
      consistent assessment of homogeneity of treatment effect before pooling. The
      random effect model assumes that the distribution of the treatment effect is
      fully heterogenous across the experiments. However, other models arising by
      grouping some of the experiments are plausible. We illustrate on simulated binary
      experiments that the fully heterogenous model gives a poor meta-inference when
      fully heterogeneity is not the true model and that the knowledge of the true
      cluster model considerably improves the inference. We propose the use of a
      Bayesian model selection procedure for estimating the true cluster model, and
      Bayesian model averaging to incorporate into the meta-analysis the clustering
      estimation. A well-known meta-analysis for six major multicentre trials to assess
      the efficacy of a given dose of aspirin in post-myocardial infarction patients is
      reanalysed.

PMID- 28511614
TI  - A new topical panthenol-containing emollient for maintenance treatment of
      childhood atopic dermatitis: results from a multicenter prospective study.
AB  - PURPOSE: A study was conducted with a new topical panthenol-containing emollient
      (NTP-CE) to investigate the efficacy and safety of a 3-month maintenance
      treatment in infants and children with stabilized mild atopic dermatitis (AD).
      METHODS: After the stabilization phase (up to 2 months) using a corticosteroid
      free topical medical device, 108 subjects (aged 2-49 months) with a SCORing AD
      (SCORAD) on the target area of <5, were randomized to receive NTP-CE (N = 52) or
      reference emollient (N = 56) twice-daily for ~3 months. SCORAD scores, occurrence
      of flares, and tolerability were assessed at regular intervals. RESULTS: In both
      groups, local SCORAD decreased during the study with a mean change from baseline
      (=end of stabilization phase) of -1.2 +/- 1.3 (NTP-CE) and -1.0 +/- 1.9. Kaplan
      Meier analysis provided success rates (i.e. proportion of subjects without flares
      at study end) of 96 and 77% for the NTP-CE and reference group, respectively (p
      =.083, log-rank test). Mean time to flare-up was 47 days (range: 29-65) in the
      NTP CE group and 50 days (6-100). Study products were well tolerated.
      CONCLUSIONS: Our results indicate that NTP-CE is efficacious and safe when used
      for maintenance treatment of mild childhood AD.

PMID- 28511617
TI  - Secondary Procedures Following Iliac Branch Device Treatment of Aneurysms
      Involving the Iliac Bifurcation: The pELVIS Registry.
AB  - PURPOSE: To evaluate the incidence and reasons for secondary procedures in
      patients treated with iliac branch devices (IBDs) for isolated iliac aneurysm or
      aortoiliac aneurysms involving the iliac bifurcation. METHODS: Between January
      2005 and December 2015, 575 surgical-high-risk patients (mean age 72.0+/-8.4
      years; 558 men) with isolated iliac aneurysms (n=79) or aortoiliac aneurysms
      involving the iliac bifurcation (n=496) were treated with placement of 650 ZBIS
      or Gore IBDs (75 bilateral) in 6 European centers. The primary outcome was
      procedure-related reinterventions for occlusion or high-grade (>70%) stenosis of
      the bridging device, occlusion of the ipsilateral common or external iliac artery
      (EIA), type I/III endoleak, rupture, or infection following IBD implantation.
      Clinical and radiological data were analyzed based on preset definitions of
      comorbidities, aneurysm morphology, intraoperative variables, and follow-up
      strategies. RESULTS: Nine (1.6%) reinterventions were performed within 30 days
      for occlusion or endoleak. Among 10 (1.5%) occluded EIAs ipsilateral to a
      deployed IBD, 6 underwent a reintervention with additional stent placement after
      thrombolysis (n=4) or a femorofemoral or iliofemoral crossover bypass (n=2).
      Three of 14 patients with early type I endoleak had a reintervention for an
      insufficient proximal sealing zone (stent-grafts in 2 common iliac arteries and 1
      bifurcated endograft). Mean clinical and radiological follow-up were 32.6+/-9.9
      and 29.8+/-21.1 months, respectively. Forty-two (7.3%) patients underwent
      reinterventions in the follow-up period. The overall postoperative reintervention
      rate was 8.9%. Both external and common iliac segments occluded in 30 (4.6%)
      IBDs; 2 patients had a crossover bypass and 14 were treated with endovascular
      techniques. In the other 14 patients, no specific treatment was performed. Seven
      (1.2%) patients with isolated EIA occlusion were treated during follow-up.
      Nineteen of the overall 28 patients with type I endoleak underwent endovascular
      repair. The other 9 were under radiological surveillance due to less significant
      (<5 mm) sac increase. No reintervention was performed to recanalize 11 (1.6%)
      occluded internal iliac arteries. CONCLUSION: Midterm experience with placement
      of IBDs is associated with a low incidence of secondary procedures due to type I
      endoleaks and occlusions. The main reasons for reinterventions seem to be short
      proximal sealing zone and poor conformability of the ZBIS device in elongated
      EIAs.

PMID- 28511619
TI  - Daylight photodynamic therapy in Scotland.
AB  - Chronic sun-induced dysplastic skin changes (actinic keratoses) are extremely
      common in fair-skinned people in Scotland. These changes are a major cause of
      morbidity and may develop into skin cancer. Actinic keratoses are often extensive
      and pose a therapeutic challenge as field-directed treatment is required for
      chronic disease management. One such treatment approach is hospital-based
      photodynamic therapy, which is a well-established treatment in Scotland for
      actinic keratoses, using a photosensitiser pro-drug and red LED light
      irradiation. However, photodynamic therapy using daylight as the activating light
      source is increasingly and effectively used in continental Europe, but had not
      been explored in Scotland until we initiated this in 2013. We report our
      experience of daylight photodynamic therapy in 64 patient-treatment courses and
      demonstrate that this can be an effective, well-tolerated treatment, which is
      liked by patients. Our most recent data show that most patients (73%) achieved
      clearance or at least a good response to treatment and had high levels of
      satisfaction with daylight photodynamic therapy. Daylight exposure measurements
      indicated that treatment is feasible in Scotland between April to September.
      Daylight photodynamic therapy is an important advancement in treatment options
      for Scottish patients with extensive pre-cancerous field changes and provides
      opportunities for home-based treatment and increased efficiency of photodynamic
      therapy services.

PMID- 28511618
TI  - Midterm Results of Low-Profile Stents to Treat Atherosclerotic Iliac Artery
      Disease.
AB  - PURPOSE: To evaluate the safety and effectiveness of low-profile 4-F stents for
      the treatment of atherosclerotic iliac artery lesions. METHODS: Between January
      2009 and December 2015, 63 patients (mean age 69.3 years; 42 men) received low
      profile stents (Astron Pulsar or Pulsar-18) at the discretion of the operator to
      treat iliac artery occlusive disease. The majority of patients (40, 63.5%) had
      critical limb ischemia; 36 of 82 lesions were total occlusions. All procedures
      were performed with 4-F equipment. Outcomes evaluated included mortality, patency
      (primary, assisted primary, and secondary), absence of target lesion
      revascularization (TLR), and limb salvage. Associations of patient and procedure
      variables with patency and TLR outcomes were sought with univariate and
      multivariate analysis. RESULTS: Via a brachial (n=46/63) or femoral (n=17/63)
      access, 82 stents were successfully deployed to treat the 82 lesions, with <30%
      residual stenosis. The overall access-related complication rate was 1.6%
      (brachial artery occlusion). Mean duration of follow-up was 24.1+/-22.3 months
      (range 1-72), during which 3 patients died and 1 major amputation occurred at 10
      months. The 4-year Kaplan-Meier estimate of primary patency was 76.9% (95% CI
      70.2% to 83.6%); the assisted primary and secondary patency estimates were 79.3%
      (95% CI 73% to 85.6%) and 91% (95% CI 84.5% to 97.5%). The 4-year freedom from
      TLR estimate was 73.8% (95% CI 67.4% to 80.2%). On multivariate analysis, the
      only associations confirmed involved Rutherford category 5/6 with primary patency
      (hazard ratio [HR] 5.7, 95% CI 4.4 to 7, p=0.02) and assisted primary patency (HR
      6.1, 95% CI 4.9 to 7.3, p=0.01). CONCLUSION: Use of a low-profile 4-F stent in
      atherosclerotic iliac lesions was safe and effective. At 4 years, the overall
      patency and the absence of TLR were good. Midterm outcomes were poor in patients
      with Rutherford category 5/6 ischemia. Finally, the use of stents with a >=6-mm
      diameter and postdeployment balloon dilation are recommended in all cases.

PMID- 28511620
TI  - Is children's listening effort in background noise influenced by the speaker's
      voice quality?
AB  - The present study aims at exploring the influence of voice quality on listening
      effort in children performing a language comprehension test with sentences of
      increasing difficulty. Listening effort is explored in relation to gender ( =
      cisgender). The study has a between-groups design. Ninety-three mainstreamed
      children aged 8;2 to 9;3 with typical language development participated. The
      children were randomly assigned to two groups (n = 46/47) with equal allocation
      of boys and girls and for the analysis to four groups depending of gender and
      voice condition. Working memory capacity and executive functions were tested in
      quiet. A digital version of a language comprehension test (the TROG-2) was used
      to measure the effect of voice quality on listening effort, measured as response
      time in a forced-choice paradigm. The groups listened to sentences through
      recordings of the same female voice, one group with a typical voice and one with
      a dysphonic voice, both in competing multi-talker babble noise. Response times
      were logged after a time buffer between the sentence-ending and indication of
      response. There was a significant increase in response times with increased task
      difficulty and response times between the two voice conditions differed
      significantly. The girls in the dysphonic condition were slower with increasing
      task difficulty. A dysphonic voice clearly adds to the noise burden and listening
      effort is greater in girls than in boys when the teacher speaks with dysphonic
      voice in a noisy background. These findings might mirror gender differences as
      for coping strategies in challenging contexts and have important implications for
      education.

PMID- 28511621
TI  - The effect of exercise training on characteristics of exercise oscillatory
      ventilation in chronic heart failure - Reply to the Letter to the Editor.

PMID- 28511622
TI  - The effect of exercise training on exercise oscillatory ventilation in heart
      failure.

PMID- 28511624
TI  - Ten Years After.

PMID- 28511625
TI  - Effects of Smoking on Clinical Foot and Ankle Practice.

PMID- 28511627
TI  - Short interpregnancy intervals and associated risk of preterm birth in Asians and
      Pacific Islanders.
AB  - PURPOSE: The prevalence of short interpregnancy intervals (IPIs) and associated
      rates of preterm birth has been understudied in Asian and Pacific Islander
      populations. We sought to estimate rates of short IPI among Asian subgroups and
      Pacific Islanders and associated risk of preterm birth. MATERIALS AND METHODS:
      For this retrospective cohort study, we linked records of women in California
      with a first birth in 1999-2000 and a second birth before 2005 with hospital
      discharge data. We used multivariate modeling to determine whether specific Asian
      ethnicities and Pacific Islanders were at greater risk of short IPI (<6 months, 6
      18 months) and if a short IPI increased risk for preterm birth in these groups.
      RESULTS: Our sample included 189,931 women. In multivariable analyses, Asian
      subgroups and Pacific Islanders were more likely to have an IPI <6 months than
      were White women (Pacific Islanders: OR 3.31 (95%CI [2.7, 4.1]); Filipinas: OR
      1.51 (95%CI [1.33, 1.71]); Southeast Asians: OR 1.93 (95%CI [1.73, 2.1]); East
      Asians: OR 1.65 (95%CI [1.48, 1.84]); other Asians: OR 2.04 (95%CI [1.70, 2.4])).
      CONCLUSIONS: Asian and Pacific Islander women have higher rates of IPI <6 months,
      but this did not significantly increase their risk of preterm birth.

PMID- 28511629
TI  - Letter to the Editor Re: Zeidman LA, Stone J, Kondziella D. New revelations about
      Hans Berger, father of the electroencephalogram (EEG), and his ties to the Third
      Reich. J Child Neurol. 2014;29:1002-1010.

PMID- 28511631
TI  - Reversible Cerebral Vasoconstriction Syndrome in Pediatrics: A Case Series and
      Review.
AB  - Reversible cerebral vasoconstriction syndrome is a transient vasculopathy
      associated with severe headaches and stroke. In most cases of reversible cerebral
      vasoconstriction syndrome, there is a precipitating event or trigger, such as
      pregnancy, serotonin agonist treatment or illicit drug use. The authors present 2
      pediatric cases of reversible cerebral vasoconstriction syndrome and review the
      previous 11 pediatric cases in the literature. In many instances, the clinical
      and radiographic features are similar in both pediatric and adult cases. In the
      pediatric group, reported potential triggers include trauma (1/13), exercise
      (2/13), water to the face (3/13), hypertension (3/13), and medication or
      substance use (4/13). One surprising difference is that 11 out of 13 pediatric
      patients with reversible cerebral vasoconstriction syndrome are male while most
      cases in adults are female. Many of the pediatric patients with reversible
      cerebral vasoconstriction syndrome were treated with a calcium channel blocker
      and the overall outcome of pediatric reversible cerebral vasoconstriction
      syndrome was good, with most patients experiencing a full recovery.

PMID- 28511630
TI  - Corpus Callosotomy for Intractable Epilepsy Revisited: The Children's Hospital of
      Michigan Series.
AB  - Corpus callosotomy is a palliative procedure performed to reduce the severity of
      drug-resistant epilepsy. The authors assessed its efficacy on different seizure
      types in 20 subjects (age range 5-19 years); 8 with active vagus nerve
      stimulator. Fifteen had complete callosotomy, 3 had anterior 2/3, and 2 had
      anterior 2/3 followed later by complete callosotomy. Ten had endoscopic approach.
      In all, 65% had >= 50% reduction of generalized seizures leading to falls
      (atonic, tonic, myoclonic); 35% became seizure-free (follow-up period: 6 months
      to 9 years; mean 3 years). Seizure outcome distribution was better for
      generalized than for partial seizures ( P = .003). Endoscopic approach was as
      effective as transcranial approach. Seven subjects who failed vagus nerve
      stimulator therapy responded with >=50% seizure reduction. Corpus callosotomy is
      an effective treatment for intractable generalized epilepsy leading to falls with
      significant seizure reduction or even elimination of seizures, in the majority of
      children.

PMID- 28511632
TI  - Mislabeling of Study Design and Overstatement of Findings in "Rechallenging
      Statin Therapy in Veterans With Statin-Induced Myopathy Post Vitamin D
      Replenishment".

PMID- 28511633
TI  - Authors' Response.

PMID- 28511634
TI  - Human factors considerations in designing for infection prevention and control in
      neonatal care - findings from a pre-design inquiry.
AB  - Qualitative data collection methods drawn from the early stages of human-centred
      design frameworks combined with thematic analysis were used to develop an
      understanding of infection prevention practice within an existing neonatal
      intensive care unit. Findings were used to generate a framework of understanding
      which in turn helped inform a baseline approach for future research and design
      development. The study revealed that a lack of clarity between infection
      transmission zones and a lack of design attributes needed to uphold infection
      prevention measures may be undermining healthcare workers' understanding and
      application of good practice. The issue may be further complicated by well
      intentioned behavioural attitudes to meeting work objectives; undue influences
      from spatial constraints; the influence of inadvertent and excessive touch-based
      interactions; physical and/or cognitive exertion to maintain transmission
      barriers; and the impact of expanding job design and increased workload to
      supplement for lack of effective barriers. Practitioner Summary: Despite high
      hand hygiene compliance within a neonatal intensive care unit, healthcare workers
      expressed concerns about the unit design and infection prevention practice. Early
      inquiry methods from human-centred design and thematic analysis helped develop a
      framework to understand how design can be used to aid infection prevention.

PMID- 28511635
TI  - Review of Techniques to Achieve Optical Surface Cleanliness and Their Potential
      Application to Surgical Endoscopes.
AB  - A clear visualization of the operative field is of critical importance in
      endoscopic surgery. During surgery the endoscope lens can get fouled by body
      fluids (eg, blood), ground substance, rinsing fluid, bone dust, or smoke plumes,
      resulting in visual impairment. As a result, surgeons spend part of the procedure
      on intermittent cleaning of the endoscope lens. Current cleaning methods that
      rely on manual wiping or a lens irrigation system are still far from ideal,
      leading to longer procedure times, dirtying of the surgical site, and reduced
      visual acuity, potentially reducing patient safety. With the goal of finding a
      solution to these issues, a literature review was conducted to identify and
      categorize existing techniques capable of achieving optically clean surfaces, and
      to show which techniques can potentially be implemented in surgical practice. The
      review found that the most promising method for achieving surface cleanliness
      consists of a hybrid solution, namely, that of a hydrophilic or hydrophobic
      coating on the endoscope lens and the use of the existing lens irrigation system.

PMID- 28511636
TI  - HPV prevalence and type distribution in Cypriot women with cervical cytological
      abnormalities.
AB  - BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted
      agent, and it can cause cervical lesions and cancer in females. Currently,
      information regarding the prevalence of HPV in Cyprus is lacking. The aim of this
      study was to evaluate the HPV type-specific prevalence in 596 women, aged 19-65
      years, with cytological abnormalities. Additionally, in a subset of 348 women for
      whom cytology results of the Pap test were available, the association between HPV
      infection and cervical disease was investigated. METHODS: HPV detection and
      typing was carried out using PCR and restriction fragment length polymorphism
      analysis, respectively. RESULTS: Overall, the HPV prevalence was 72.8%, and it
      was shown to be age dependent, with a decreasing prevalence until the age of 45
      years (p = 0.0018, chi2). Two hundred and fifty-eight women (59.4%) were infected
      with high-risk HPV, 151 (34.8%) with low-risk HPV, and 25 (5.8%) with HPV types
      of unknown risk. The most common high-risk HPV type was HPV16 (17.7%), followed
      by HPV31 (12.9%), HPV58 (7.1%), HPV68 (4.6%), HPV18 (4.1%), and HPV56 (3.7%).
      Among the women for whom cytology results were available, 268 (77%) were HPV
      positive, with a sample distribution as follows: 188 (74%) had atypical squamous
      cells of undetermined significance (ASCUS), 61 (85.9%) had low-grade squamous
      intraepithelial lesion (L-SIL), and 19 (82.6%) had high-grade squamous
      intraepithelial lesion (H-SIL). HPV16 was the most common type among women
      affected by L-SIL (19.7%) and H-SIL (15.8%), with HPV31 being the most common
      type in women affected by ASCUS (16.5%). CONCLUSIONS: The present study provides
      the first epidemiological data related to HPV prevalence and type distribution in
      Cypriot women with cytological abnormalities.

PMID- 28511637
TI  - The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and
      severity of, chronic ITP.
AB  - BACKGROUND: T-helper cell type 1 (Th1) polarization in chronic immune
      thrombocytopenia (cITP) has been reported at the protein and mRNA levels. We
      evaluated the impact of Th1/Th2 cytokine and cytokine receptor functional
      polymorphisms on both susceptibility to, and severity of, cITP. We analysed IFN
      gamma + 874 T/A, IFN-gammaR -611G/A, IL-4 -590C/T, and IL-4Ralpha Q576R
      polymorphisms in 126 cITP patients (male/female: 34/92; median age: 47.7 years)
      and 202 healthy control donors. Genotyping was determined by PCR and direct
      sequencing. The Th1/Th2 ratio was detected in peripheral blood mononuclear cells
      via flow cytometry. RESULTS: cITP patients had a higher frequency of the IL
      4Ralpha 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP
      patients with the IFN-gamma +874 non-AA genotype (high expression type) showed
      more severe thrombocytopenia than those with the AA genotype (P < 0.05). cITP
      patients had a significantly higher Th1/Th2 ratio than control patients (P <
      0.01); this ratio was inversely correlated with platelet counts. Furthermore,
      patients with both IFN-gamma +874 non-AA genotype (high expression type) and IFN
      gammaR -611 non-AA genotype (high-function type) had a significantly higher
      Th1/Th2 ratio (P < 0.05). CONCLUSIONS: The cytokine polymorphisms affecting
      Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.

PMID- 28511638
TI  - Screening for tuberculosis in an urban shelter for homeless in Switzerland: a
      prospective study.
AB  - BACKGROUND: Whereas high risk groups such as asylum seekers are systematically
      screened for active tuberculosis (TB) upon entry in Switzerland, this strategy
      does not apply to homeless persons despite a reported high risk. Geneva health
      and social authorities implemented an intersectoral project to screen for active
      TB in homeless persons. We aimed to assess acceptability of this program and
      prevalence of active TB in this group. METHODS: This prospective study targeted
      all homeless adults registering for shelter accommodation in Geneva during winter
      2015. Applicants were proposed a questionnaire-based screening ( www.tb-screen.ch
      ) exploring epidemiological and clinical risk factors for active TB. Participants
      with a positive score underwent diagnostic procedures at Geneva University
      Hospital. Enhanced TB surveillance targeting homeless persons in the community
      was continued 3 months after the study termination. RESULTS: Overall, 726/832
      (87.3%) homeless persons accepted the screening procedure. Most were young male
      migrants without access to care in Switzerland. Male gender (adjusted OR: 2.14;
      95% confidence interval: 1.27-3.62), age below 25 years (aOR: 4.16; 95% CI: 1.27
      13.64) and short duration of homelessness (aOR: 1.75; 95% CI: 1.06-2.87) were
      predictors of acceptance. Thirty (4.1%) had positive screening scores but none of
      the 24 who underwent further testing had active TB. Post-study surveillance did
      not identify any incident case in Geneva. CONCLUSIONS: Active TB screening
      targeting highly mobile homeless persons in shelters was well accepted and
      feasible. The participants' sociodemographic profile highlighted the
      heterogeneity of homeless groups in Europe and the null TB prevalence the
      variability of their active TB risks. These findings underline the feasibility of
      health programs targeting this hard to reach group and the need for close
      monitoring of this social group considering the rapid changes in international
      mobility patterns to tailor preventive and screening strategies to the local
      context.

PMID- 28511639
TI  - Physical activity among hospitalized older adults - an observational study.
AB  - BACKGROUND: Low level of physical activity is common among hospitalized older
      adults and is associated with worse prognosis. The aim of this paper is to
      describe the pattern and level of physical activity in a group of hospitalized
      older adults and to identify factors associated with physical activity. METHODS:
      We measured physical activity on day three after admission using accelerometer
      based activity monitors and time in upright position as outcome measure. We
      collected data of physical function (Short Physical Performance Battery, SPPB. 0
      12), cognitive function (Mini Mental Status Examination, MMSE, 0-30 and diagnosis
      of cognitive impairment at discharge, yes/no), personal Activities of Daily
      Living (p-ADL, Barthel Index, BI, 0-20) and burden of disease (Cumulative Illness
      Rating Scale, CIRS, 0-56). We analyzed data using univariable and multivariable
      linear regression models, with time in upright position as dependent variable.
      RESULTS: We recorded physical activity in a consecutive sample of thirty-eight
      geriatric patients. Their (mean age 82.9 years, SD 6.3) mean time in upright
      position one day early after admission was 117.1 min (SD 90.1, n = 38). Mean SPPB
      score was 4.3 (SD 3.3, n = 34). Mean MMSE score was 19.3 (SD 5.3, n = 30), 73%
      had a diagnosis of cognitive impairment (n = 38). Mean BI score was 16.4 (SD 4.4,
      n = 36). Mean CIRS score was 17.0 (SD 4.2, n = 38). There was a significant
      association between SPPB score and time in upright position (p = 0.048): For each
      one unit increase in SPPB, the expected increase in upright time was 11.7 min.
      There was no significant association between age (p = 0.608), diagnosis of
      cognitive impairment (p = 0.794), p-ADL status (p = 0.127), CIRS score (p =
      0.218) and time in upright position. The overall model fit was R2 0.431.
      CONCLUSION: Participants' mean time in upright position one day early after
      admission was almost two hours, indicating a high level of physical activity
      compared to results from similar studies. Physical function was the only variable
      significantly associated with physical activity indicating that SPPB could be a
      useful screening tool and that mobilization regimes should be delivered routinely
      for patients with reduced physical function.

PMID- 28511640
TI  - Tryptophan catabolism and immune activation in primary and chronic HIV infection.
AB  - BACKGROUND: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and
      linked to immune activation. We hypothesized that early cART initiation results
      in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR
      prior to cART is a predictor of the magnitude of subsequent reduction in immune
      activation. METHODS: Prospective study including 57 HIV-infected individuals
      (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/MUL, N =
      24), late presenters (<200 CD4+ T cells/MUL, N = 19)). Kynurenine and tryptophan
      were analysed by liquid chromatography-tandem mass spectrometry. Total CD4+ and
      CD8+ T cells were determined and proportion of activated CD38 + HLA-DR+ Tcells
      was measured using flow cytometry at baseline and after 6 and 12 months of cART.
      RESULTS: At baseline, primary HIV infection had higher KTR than early presenters.
      However, similar KTR in primary HIV infection and early presenters was found
      after cART initiation, while late presenters had higher KTR at all time points.
      In primary HIV infection and early presenters, KTR was positively associated with
      proportion of activated cells at baseline. Furthermore, in early presenters the
      KTR at baseline was associated with proportion of activated cells after 6 and 12
      months. Interestingly, in primary HIV infection the KTR at baseline was
      positively associated with reduction in proportion of CD8 + CD38 + HLA-DR T cells
      after 6 and 12 months. CONCLUSIONS: Lower kynurenine/tryptophan ratio during
      follow-up was found after early initiation of cART. KTR in primary HIV infection
      and early presenters was positively associated with immune activation.
      Importantly, KTR in primary HIV infection predicted the magnitude of subsequent
      reduction in immune activation. Thus, a beneficial effect of early cART on KTR
      was suggested.

PMID- 28511641
TI  - Network-based regularization for high dimensional SNP data in the case-control
      study of Type 2 diabetes.
AB  - BACKGROUND: Over the past decades, the prevalence of type 2 diabetes mellitus
      (T2D) has been steadily increasing around the world. Despite large efforts
      devoted to better understand the genetic basis of the disease, the identified
      susceptibility loci can only account for a small portion of the T2D heritability.
      Some of the existing approaches proposed for the high dimensional genetic data
      from the T2D case-control study are limited by analyzing a few number of SNPs at
      a time from a large pool of SNPs, by ignoring the correlations among SNPs and by
      adopting inefficient selection techniques. METHODS: We propose a network
      constrained regularization method to select important SNPs by taking the linkage
      disequilibrium into account. To accomodate the case control study, an iteratively
      reweighted least square algorithm has been developed within the coordinate
      descent framework where optimization of the regularized logistic loss function is
      performed with respect to one parameter at a time and iteratively cycle through
      all the parameters until convergence. RESULTS: In this article, a novel approach
      is developed to identify important SNPs more effectively through incorporating
      the interconnections among them in the regularized selection. A coordinate
      descent based iteratively reweighed least squares (IRLS) algorithm has been
      proposed. CONCLUSIONS: Both the simulation study and the analysis of the Nurses's
      Health Study, a case-control study of type 2 diabetes data with high dimensional
      SNP measurements, demonstrate the advantage of the network based approach over
      the competing alternatives.

PMID- 28511642
TI  - Impact of a workplace 'sit less, move more' program on efficiency-related
      outcomes of office employees.
AB  - BACKGROUND: Few studies have examined the impact of 'sit less, move more'
      interventions on workplace performance. This study assessed the short and mid
      term impacts of and patterns of change within, a 19-week workplace web-based
      intervention (Walk@WorkSpain; W@WS; 2010-11) on employees' presenteeism, mental
      well-being and lost work performance. METHODS: A site randomised control trial
      recruited employees at six Spanish university campuses (n = 264; 42 +/- 10 years;
      171 female), assigned by worksite and campus to an Intervention (IG; used W@WS; n
      = 129; 87 female) or an active Comparison group (A-CG; pedometer, paper diary and
      self-reported sitting time; n = 135; 84 female). A linear mixed model assessed
      changes between the baseline, ramping (8 weeks), maintenance (11 weeks) and
      follow-up (two months) phases for the IG versus A-CG on (i) % of lost work
      productivity (Work Limitations Questionnaire; WLQ); (ii) three scales for
      presenteeism (WLQ) assessing difficulty meeting scheduling demands (Time),
      performing cognitive and inter-personal tasks (Mental-Interpersonal) and
      decrements in meeting the quantity, quality and timeliness of completed work
      (Output); and (iii) mental well-being (Warwick-Edinburgh Mental Well-being
      Scale). T-tests assessed differences between groups for changes on the main
      outcomes. In the IG, a multivariate logistic regression model identified patterns
      of response according to baseline socio-demographic variables, physical activity
      and sitting time. RESULTS: There was a significant 2 (group) * 2 (program time
      points) interaction for the Time (F [3]=8.69, p = 0.005), Mental-Interpersonal (F
      [3]=10.01, p = 0.0185), Output scales for presenteeism (F [3]=8.56, p = 0.0357),
      and for % of lost work performance (F [3]=10.31, p = 0.0161). Presenteeism and
      lost performance rose significantly in both groups across all study time points;
      after baseline performance was consistently better in the IG than in the A-CG.
      Better performance was linked to employees being more active (Time, p = 0.041)
      and younger (Mental-interpersonal, p = 0.057; Output, p = 0.017). Higher total
      sitting time during nonworking days (Mental-interpersonal, p = 0.019) and lower
      sitting time during workdays (WLQ Index, p = 0.013) also improved performance.
      CONCLUSION: Versus an active comparison condition, a 'sit less, move more'
      workplace intervention effectively reduced an array of markers of lost workday
      productivity. TRIAL REGISTRATION: NCT02960750 ; Date of registration: 07/11/2016.

PMID- 28511643
TI  - Long noncoding RNA expression profile in HLE B-3 cells during TGF-beta2-induced
      epithelial-mesenchymal transition.
AB  - BACKGROUND: Recent evidence has shown that long noncoding RNAs (lncRNAs) are
      involved in the process of epithelial-mesenchymal transition (EMT). However,
      little research has focused on the expression profile of lncRNAs during EMT in
      human lens epithelial cells (LECs) and their functions have not yet been
      described. METHODS: Dysregulated lncRNAs and mRNAs in normal human lens
      epithelial B-3(HLE B-3) cells and during transforming growth factor beta2(TGF
      beta2)-induced EMT were analyzed via lncRNA microarray. Gene Ontology (GO) and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analyses of differentially
      expressed mRNAs were performed to identify their functions and pathologic
      pathways. Six candidate lncRNAs were validated via quantitative real-time reverse
      transcription polymerase chain reaction(qRT-PCR) to confirm the microarray data.
      RESULTS: A total of 775 lncRNAs (325 up-regulated and 450 down-regulated) and 935
      mRNAs (329 up-regulated and 606 down-regulated) were differentially expressed in
      HLE B-3 cells during TGF-beta2-induced EMT compared to normal HLE B-3 cells. GO
      and KEGG Pathway analyses indicated the functions of differentially expressed
      mRNAs in the TGF-beta2-induced EMT in HLE B-3 cells. qRT-PCR confirmed the trends
      indicated in microarray analysis for all 6 candidate lncRNAs. CONCLUSION: Our
      study lays the foundation for future research in lncRNAs related to EMT in HLE B
      3 cells and could provide new avenues for the prevention and treatment of
      posterior capsule opacification (PCO).

PMID- 28511644
TI  - Relationship between Glycemic Levels and Treatment Outcome among Critically Ill
      Children admitted into Emergency Room in Enugu.
AB  - BACKGROUND: Critically ill children are those in need of immediate attention on
      arrival to an emergency room. The importance of glycemic level measurement as
      well as maintaining the patency of the airway, effective breathing and
      circulation cannot be overemphasied. It has been highlighted that the peak
      hyperglycemia and hypoglycemia predict poor prognosis, longer lengths of hospital
      stay and higher mortality. The study aims to assess the relationship between
      glycemic level and treatment outcomes as well as length of hospital stay.
      METHODS: Analytical cross sectional method was used to study critically ill
      children aged >=1 month to <=10 years admitted into the Children Emergency Room
      of Enugu State University Teaching Hospital, Enugu. Their admission blood glucose
      was done. Interviewer administered questionnaire was used to collect information
      including sociodemographics, duration of hospitalization and outcome of
      treatment. Data was analysed using SPSS version 20. Chi square, logistic
      regressions and Kruskal Wallis tests were done as appropriate. RESULTS: A total
      of 300 patients were recruited. One hundred and seventeen (39%) had
      hyperglycemia, 62 (20.7%) patients had hypoglycaemia and 121 (40.3%) had
      euglycemia. Two hundred and fifty two (84%) were discharged while 48 (16%) died.
      There was significant association between glycemic levels and treatment outcome
      (p = < 0.001). Among the 48 who died, 12 (25.0%) had euglycemia, 21 (43.75%) had
      hypoglycaemia while 15 (31.25%) had hyperglycemia. On multivariate analysis,
      there was statistically significant association between hypoglycaemia and
      mortality (p = < 0.001). Unadjusted, those children with hypoglycaemia at
      presentation were about 4.7 times (UOR = 0.21, 95% Cl: 0.08-0.38) and adjusted,
      about 5 times (AOR = 0.20, 95% CI: 0.09-0.47) less likely to survive compared
      with those with euglycemia. Although not statistically significant, those with
      hyperglycemia were about 1.3 times less likely to survive compared with
      euglycemic children, adjusted and unadjusted (UOR = 0.75, 95% Cl: 0.33-1.68).
      CONCLUSION: While both hypo- and hyperglycemia are associated with mortality,
      hypoglycaemia had a greater effect than hyperglycemia. Glycemic levels
      significantly affects treatment outcome.

PMID- 28511645
TI  - Therapeutic potential of TAS-115 via c-MET and PDGFRalpha signal inhibition for
      synovial sarcoma.
AB  - BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue
      sarcoma, remains poor. We previously reported that c-MET or platelet-derived
      growth factor receptor alpha (PDGFRalpha) signalling pathway is related to SS
      progression based upon the findings of phospho-receptor tyrosine kinase (RTK)
      arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor
      targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs.
      Here we aimed to investigate the therapeutic potential of TAS-115 against SS.
      METHODS: We first evaluated which signalling pathway was relevant to the
      viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we
      assessed the anticancer activity and mechanism of action of TAS-115 in these SS
      cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and
      PDGFRalpha phosphorylation with that of pazopanib. RESULTS: We classified the SS
      cell lines as c-MET-dependent or PDGFRalpha-dependent based upon the differences
      in the signalling pathway relevant for growth and/or survival. We also found that
      c-MET and PDGFRalpha were the primary activators of both phosphatidylinositol 3
      kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and
      PDGFRalpha-dependent SS cells, respectively. TAS-115 treatment blocked the
      phosphorylation of PDGFRalpha as well as that of c-MET and their downstream
      effectors, leading to marked growth inhibition in both types of SS cell lines in
      in vitro and in vivo studies. Furthermore, PDGFRalpha phosphorylation, on at
      least four representative autophosphorylation sites, was impeded by TAS-115
      equivalently to pazopanib. CONCLUSIONS: These experimental results have
      demonstrated the significance of c-MET and PDGFRalpha signalling for growth
      and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose
      tumours are dependent upon either c-MET or PDGFRalpha signalling by functioning
      as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRalpha
      pathways.

PMID- 28511646
TI  - Emergence of microbial diversity due to cross-feeding interactions in a spatial
      model of gut microbial metabolism.
AB  - BACKGROUND: The human gut contains approximately 1014 bacteria, belonging to
      hundreds of different species. Together, these microbial species form a complex
      food web that can break down nutrient sources that our own digestive enzymes
      cannot handle, including complex polysaccharides, producing short chain fatty
      acids and additional metabolites, e.g., vitamin K. Microbial diversity is
      important for colonic health: Changes in the composition of the microbiota have
      been associated with inflammatory bowel disease, diabetes, obesity and Crohn's
      disease, and make the microbiota more vulnerable to infestation by harmful
      species, e.g., Clostridium difficile. To get a grip on the controlling factors of
      microbial diversity in the gut, we here propose a multi-scale, spatiotemporal
      dynamic flux-balance analysis model to study the emergence of metabolic diversity
      in a spatial gut-like, tubular environment. The model features genome-scale
      metabolic models (GEM) of microbial populations, resource sharing via
      extracellular metabolites, and spatial population dynamics and evolution.
      RESULTS: In this model, cross-feeding interactions emerge readily, despite the
      species' ability to metabolize sugars autonomously. Interestingly, the community
      requires cross-feeding for producing a realistic set of short-chain fatty acids
      from an input of glucose, If we let the composition of the microbial
      subpopulations change during invasion of adjacent space, a complex and stratified
      microbiota evolves, with subspecies specializing on cross-feeding interactions
      via a mechanism of compensated trait loss. The microbial diversity and
      stratification collapse if the flux through the gut is enhanced to mimic
      diarrhea. CONCLUSIONS: In conclusion, this in silico model is a helpful tool in
      systems biology to predict and explain the controlling factors of microbial
      diversity in the gut. It can be extended to include, e.g., complex nutrient
      sources, and host-microbiota interactions via the intestinal wall.

PMID- 28511647
TI  - Low-smoke chulha in Indian slums: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Biomass fuel is used as a primary cooking source by more than half of
      the world's population, contributing to a high burden of disease. Although
      cleaner fuels are available, some households continue using solid fuels because
      of financial constraints and absence of infrastructure, especially in non
      notified slums. The present study documents a randomised controlled study
      investigating the efficacy of improved cookstove on the personal exposure to air
      pollution and the respiratory health of women and children in an Indian slum. The
      improved cookstove was based on co-creation of a low-smoke chulha with local
      communities in order to support adaption and sustained uptake. METHODS: The study
      will be conducted in a non-notified slum called Ashrayanagar in Bangalore, India.
      The study design will be a 1:1 randomised controlled intervention trial,
      including 250 households. The intervention group will receive an improved
      cookstove (low-smoke chulha) and the control group will continue using either the
      traditional cookstove (chulha) or a combination of the traditional stove and the
      kerosene/diesel stove. Follow-up time is 1 year. Outcomes include change in lung
      function (FEV1/FVC), incidence of pneumonia, change in personal PM2.5 and CO
      exposure, incidence of respiratory symptoms (cough, phlegm, wheeze and shortness
      of breath), prevalence of other related symptoms (headache and burning eyes),
      change in behaviour and adoption of the stove. Ethical clearance was obtained
      from the Institutional Ethics Committee of the Indian Institute of Public Health
      Hyderabad- Bengaluru Campus. DISCUSSION: The findings from this study aim to
      provide insight into the effects of improved cookstoves in urban slums. Results
      can give evidence for the decrease of indoor air pollution and the improvement of
      respiratory health for children and women. TRIAL REGISTRATION: The trial was
      registered with clinicaltrials.gov on 21 June 2016 with the identifier
      NCT02821650 ; A Study to Test the Impact of an Improved Chulha on the Respiratory
      Health of Women and Children in Indian Slums.

PMID- 28511648
TI  - A mathematical model of mechanotransduction reveals how mechanical memory
      regulates mesenchymal stem cell fate decisions.
AB  - BACKGROUND: Mechanical and biophysical properties of the cellular
      microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate
      is influenced by past mechanical dosing (memory), but the mechanisms underlying
      this process have not yet been well defined. We have yet to understand how memory
      affects specific cell fate decisions, such as the differentiation of MSCs into
      neurons, adipocytes, myocytes, and osteoblasts. RESULTS: We study a minimal gene
      regulatory network permissive of multi-lineage MSC differentiation into four cell
      fates. We present a continuous model that is able to describe the cell fate
      transitions that occur during differentiation, and analyze its dynamics with
      tools from multistability, bifurcation, and cell fate landscape analysis, and via
      stochastic simulation. Whereas experimentally, memory has only been observed
      during osteogenic differentiation, this model predicts that memory regions can
      exist for each of the four MSC-derived cell lineages. We can predict the
      substrate stiffness ranges over which memory drives differentiation; these are
      directly testable in an experimental setting. Furthermore, we quantitatively
      predict how substrate stiffness and culture duration co-regulate the fate of a
      stem cell, and we find that the feedbacks from the differentiating MSC onto its
      substrate are critical to preserve mechanical memory. Strikingly, we show that re
      seeding MSCs onto a sufficiently soft substrate increases the number of cell
      fates accessible. CONCLUSIONS: Control of MSC differentiation is crucial for the
      success of much-lauded regenerative therapies based on MSCs. We have predicted
      new memory regions that will directly impact this control, and have quantified
      the size of the memory region for osteoblasts, as well as the co-regulatory
      effects on cell fates of substrate stiffness and culture duration. Taken
      together, these results can be used to develop novel strategies to better control
      the fates of MSCs in vitro and following transplantation.

PMID- 28511649
TI  - IL-10 ameliorates TNF-alpha induced meniscus degeneration in mature meniscal
      tissue in vitro.
AB  - BACKGROUND: Joint inflammation causes meniscus degeneration and can exacerbate
      post-traumatic meniscus injuries by extracellular matrix degradation, cellular de
      differentiation and cell death. The aim of this study was to examine whether anti
      inflammatory interleukin-10 exerts protective effects in an in vitro model of TNF
      alpha-induced meniscus degeneration. METHODS: Meniscus tissue was harvested from
      the knees of adult cows. After 24 h of equilibrium explants were simultaneously
      treated with bovine TNF-alpha and IL-10. After an incubation time of 72 h cell
      death was measured histomorphometrically (nuclear blebbing, NB) and release of
      glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were
      analysed. Transcription levels (mRNA) of matrix degrading enzymes, collagen type
      X (COL10A1) and nitric oxide synthetase 2 (NOS2) were measured by quantitative
      real time PCR. TNF-alpha-dependent formation of the aggrecanase-specific aggrecan
      neoepitope NITEGE was visualised by immunostaining. Differences between groups
      were calculated using a one-way ANOVA with a Bonferroni post hoc test. RESULTS:
      Administration of IL-10 significantly prevented the TNF-alpha-related cell death
      (P .001), release of NO (P .003) and NOS2 expression (P .04). Release of GAG
      fragments (P .001), NITEGE formation and expression of MMP3 (P .007), -13 (P .02)
      and ADAMTS4 (P .001) were significantly reduced. The TNF-alpha-dependent increase
      in COL10A1 expression was also antagonized by IL-10 (P .02). CONCLUSION: IL-10
      prevented crucial mechanisms of meniscal degeneration induced by a key cytokine
      of OA, TNF-alpha. Administration of IL-10 might improve the biological
      regeneration and provide a treatment approach in degenerative meniscus injuries
      and in conditions of post-traumatic sports injuries.

PMID- 28511650
TI  - Pain, pain intensity and pain disability in high school students are differently
      associated with physical activity, screening hours and sleep.
AB  - BACKGROUND: Studies exploring the association between physical activity, screen
      time and sleep and pain usually focus on a limited number of painful body sites.
      Nevertheless, pain at different body sites is likely to be of different nature.
      Therefore, this study aims to explore and compare the association between time
      spent in self-reported physical activity, in screen based activities and sleeping
      and i) pain presence in the last 7-days for 9 different body sites; ii) pain
      intensity at 9 different body sites and iii) global disability. METHODS: Nine
      hundred sixty nine students completed a questionnaire on pain, time spent in
      moderate and vigorous physical activity, screen based time watching TV/DVD,
      playing, using mobile phones and computers and sleeping hours. Univariate and
      multivariate associations between pain presence, pain intensity and disability
      and physical activity, screen based time and sleeping hours were investigated.
      RESULTS: Pain presence: sleeping remained in the multivariable model for the
      neck, mid back, wrists, knees and ankles/feet (OR 1.17 to 2.11); moderate
      physical activity remained in the multivariate model for the neck, shoulders,
      wrists, hips and ankles/feet (OR 1.06 to 1.08); vigorous physical activity
      remained in the multivariate model for mid back, knees and ankles/feet (OR 1.05
      to 1.09) and screen time remained in the multivariate model for the low back (OR
      = 2.34. Pain intensity: screen time and moderate physical activity remained in
      the multivariable model for pain intensity at the neck, mid back, low back,
      shoulder, knees and ankles/feet (Rp2 0.02 to 0.04) and at the wrists (Rp2 =
      0.04), respectively. Disability showed no association with sleeping, screen time
      or physical activity. CONCLUSIONS: This study suggests both similarities and
      differences in the patterns of association between time spent in physical
      activity, sleeping and in screen based activities and pain presence at 8
      different body sites. In addition, they also suggest that the factors associated
      with the presence of pain, pain intensity and pain associated disability are
      different.

PMID- 28511651
TI  - High-resolution mucociliary transport measurement in live excised large animal
      trachea using synchrotron X-ray imaging.
AB  - BACKGROUND: The Australian Synchrotron Imaging and Medical Beamline (IMBL) was
      designed as the world's widest synchrotron X-ray beam, enabling both clinical
      imaging and therapeutic applications for humans as well as the imaging of large
      animal models. Our group is developing methods for imaging the airways of newly
      developed CF animal models that display human-like lung disease, such as the CF
      pig, and we expect that the IMBL can be utilised to image airways in animals of
      this size. METHODS: This study utilised samples of excised tracheal tissue to
      assess the feasibility, logistics and protocols required for airway imaging in
      large animal models such as pigs and sheep at the IMBL. We designed an image
      processing algorithm to automatically track and quantify the tracheal mucociliary
      transport (MCT) behaviour of 103 MUm diameter high refractive index (HRI) glass
      bead marker particles deposited onto the surface of freshly-excised normal sheep
      and pig tracheae, and assessed the effects of airway rehydrating aerosols.
      RESULTS: We successfully accessed and used scavenged tracheal tissue, identified
      the minimum bead size that is visible using our chosen imaging setup, verified
      that MCT could be visualised, and that our automated tracking algorithm could
      quantify particle motion. The imaging sequences show particles propelled by
      cilia, against gravity, up the airway surface, within a well-defined range of
      clearance speeds and with examples of 'clumping' behaviour that is consistent
      with the in vivo capture and mucus-driven transport of particles. CONCLUSION:
      This study demonstrated that the wide beam at the IMBL is suitable for imaging
      MCT in ex vivo tissue samples. We are now transitioning to in vivo imaging of MCT
      in live pigs, utilising higher X-ray energies and shorter exposures to minimise
      motion blur.

PMID- 28511653
TI  - Processes and challenges of community mobilisation for latrine promotion under
      Nirmal Bharat Abhiyan in rural Odisha, India.
AB  - BACKGROUND: Despite efforts to eradicate it, open defecation remains widely
      practiced in India, especially in rural areas. Between 2013 and 2014, 50 villages
      in one district of Odisha, India, received a sanitation programme under the
      Nirmal Bharat Abhiyan (NBA - "Clean India Campaign"), the successor of India's
      Total Sanitation Campaign. This paper documents the strategies and processes of
      NBA community mobilisation for latrine promotion in these villages and assesses
      the strengths and limitations of the mobilisation activities. METHODS: NBA's
      community mobilisation activities were observed and assessed against the
      programme's theory of change in 10 randomly selected programme villages from
      start to finish. Additional data was collected through review of documents,
      individual interviews (n = 80) and focus group discussions (n = 26) with staff of
      the implementing NGOs and community members. RESULTS: Our study revealed the lack
      of a consistent implementation strategy, lack of capacities and facilitation
      skills of NGO staff to implement sanitation programmes, political interference,
      challenges in accessing government financial incentives for latrine construction,
      and lack of clarity on the roles and responsibilities among government and NGO
      staff, leading to failure in translating government policies into sustainable
      actions. Social divisions and village dynamics related to gender and caste
      further constrained the effectiveness of mobilisation activities. Meetings were
      often dominated by male members of upper caste households, and excluded low caste
      community members and views of women. Community discussions revolved largely
      around the government's cash incentive for latrines. Activities aimed at creating
      demand for sanitation and use of latrines often resonated poorly with community
      members. An assessment by the implementers, 1 year after community mobilisation
      found 19% of households had a completed latrine across the 50 villages, a
      marginal increase of 7 percentage points over baseline. CONCLUSIONS: In this
      setting, the Government of India's NBA programme to increase rural sanitation
      coverage and use is hampered by political, programmatic, logistical and socio
      structural constraints. Sanitation demand generation was difficult for local
      implementing NGOs as village populations had lost trust in organisations due to
      previous indications of fraud. Agencies or organisations implementing sanitation
      campaigns and conducting sanitation promotions need to enhance their staff's
      knowledge and build capacity in order to address important social heterogeneity
      within villages. This trial's registration number is NCT01214785 (October 4,
      2010).

PMID- 28511652
TI  - ING3 promotes prostate cancer growth by activating the androgen receptor.
AB  - BACKGROUND: The androgen receptor (AR) is a major driver of prostate cancer, and
      increased AR levels and co-activators of the receptor promote the development of
      prostate cancer. INhibitor of Growth (ING) proteins target lysine
      acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of
      active transcription, to affect chromatin structure and gene expression. ING3 is
      a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated
      in prostate cancer development. METHODS: Biopsies of 265 patients with prostate
      cancer were stained for ING3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen
      responsive cells were used for in vitro assays including immunoprecipitation,
      western blotting, Luciferase reporter assay and quantitative polymerase chain
      reaction. Cell viability and migration assays were performed in prostate cancer
      cell lines using scrambled siRNA or siRNA targeting ING3. RESULTS: We find that
      ING3 levels and AR activity positively correlate in prostate cancer. ING3
      potentiates androgen effects, increasing expression of androgen-regulated genes
      and androgen response element-driven reporters to promote growth and anchorage
      independent growth. Conversely, ING3 knockdown inhibits prostate cancer cell
      growth and invasion. ING3 activates the AR by serving as a scaffold to increase
      interaction between TIP60 and the AR in the cytoplasm, enhancing receptor
      acetylation and translocation to the nucleus. Activation is independent of ING3's
      ability to target the TIP60 complex to H3K4Me3, identifying a previously unknown
      chromatin-independent cytoplasmic activity for ING3. In agreement with in vitro
      observations, analysis of The Cancer Genome Atlas (TCGA) data (n = 498) and a
      prostate cancer tissue microarray (n = 256) show that ING3 levels are higher in
      aggressive prostate cancers, with high levels of ING3 predicting shorter patient
      survival in a low AR subgroup. Including ING3 levels with currently used
      indicators such as the Gleason score provides more accurate prognosis in primary
      prostate cancer. CONCLUSIONS: In contrast to the majority of previous reports
      suggesting tumor suppressive functions in other cancers, our observations
      identify a clear oncogenic role for ING3, which acts as a co-activator of AR in
      prostate cancer. Data from TCGA and our previous and current tissue microarrays
      suggest that ING3 levels correlate with AR levels and that in patients with low
      levels of the receptor, ING3 level could serve as a useful prognostic biomarker.

PMID- 28511655
TI  - Video vs direct laryngoscopy in the ICU: are we asking the right question?

PMID- 28511654
TI  - Oxidative profiles of LDL and HDL isolated from women with preeclampsia.
AB  - BACKGROUND: Oxidative stress causes biochemical changes in lipids and proteins;
      these changes can induce damage to the vascular endothelium and create maternal
      complications that are characteristic of preeclampsia. In this study, we
      evaluated the oxidative profile of lipoproteins isolated from women with
      preeclampsia. METHODS: Thirty women diagnosed with preeclampsia and thirty women
      without preeclampsia were included in the study. Lipid-damage biomarkers,
      including conjugated dienes, lipohydroperoxides and malondialdehyde, were
      measured. The reduction of nitroblue tetrazolium, the formation of dityrosines,
      and the carbonylation of proteins were assessed as indicators of protein damage.
      The protective activity of HDL-c was evaluated by the paraoxonase-I activity
      present on the HDL-c particles. Serum lipid profiles were also quantified in both
      groups. Data were analysed using Student's t test and the Pearson correlation
      coefficient. RESULTS: Our results demonstrated in PE women evident oxidative
      changes in the lipids and proteins in HDL-c and LDL-c particles and the activity
      of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as
      demonstrated by the negative correlation between paraoxonase-I activity and the
      formation of lipohydroperoxides in HDL-c (r = -0.3755, p < 0.005). CONCLUSIONS:
      LDL-c and HDL-c isolated from women with preeclampsia show oxidative damage to
      lipids and proteins. We propose an oxidative profile based on the oxidation
      levels indicated by each of the markers used. We also found that paraoxonase-I is
      inactivated in the presence of lipohydroperoxides. Antioxidant support might be
      helpful to reduce oxidative stress in patients with preeclampsia. Further
      investigations are necessary to define the association between antioxidant
      activities and preeclampsia.

PMID- 28511656
TI  - A randomized comparison of flow characteristics of semiskeletonized and pedicled
      internal thoracic artery preparations in coronary artery bypass.
AB  - BACKGROUND: Harvesting the internal thoracic artery (ITA) with
      semiskeletonization is an alternative technique between conventional wide pedicle
      and skeletonization. It is almost as simple as pedicle harvesting; however, it is
      supposed to provide the advantage of graft flow and length. Since the heart is
      unique being the only organ which is perfused during diastole, for comparing the
      intraoperative graft flow characteristics of semiskeletonization and pedicle
      technique, we used diastolic filling (DF) using transit-time flow measurement as
      a primary result. The objective of this study is to compare if semiskeletonized
      ITA has a greater effect on the intraoperative DF of graft flow versus
      conventional pedicled ITA in coronary artery bypass. METHODS: Between July 2015
      and May 2016, a prospective evaluation of 60 consecutive patients undergoing
      coronary artery bypass grafting for left anterior descending artery
      revascularization were randomized to having semiskeletonized (n = 30) or
      conventional pedicled (n = 30) ITA graft harvested by the same surgeon.
      Intraoperative transit-time flows were obtained. The DF of the ITA graft at the
      end of operation was evaluated in two groups. RESULTS: The intraoperative DF was
      significantly greater in the semiskeletonized grafts than in the pedicled grafts
      (70.50 +/- 14.15 versus 57.6 +/- 19.39%; p = 0.005). No statistical difference
      was observed comparing quantitative pulsatile flow and pulsatile index at the end
      of the operation in the two groups. However, the free flow of the conduit during
      the cardiopulmonary bypass before the anastomosis performed was greater in
      semiskeletonized group than in pedicled group (94 +/- 48.37 versus 56.35 +/-
      34.90 ml/min; p = 0.003). The total operative time was comparable between two
      groups (p = 0.092). CONCLUSIONS: Semiskeletonized ITA resulted in superior DF of
      left anterior descending bypass graft flow as compared with pedicled ITA. It is
      also provide a greater free flow and length of the graft without the long-delayed
      operative time. TRIAL REGISTRATION: Trial registration number (Study ID):
      TCTR20160913002 Date of registration: September 10, 2016.

PMID- 28511657
TI  - Skilled delivery inequality in Ethiopia: to what extent are the poorest and
      uneducated mothers benefiting?
AB  - BACKGROUND: The fifth Millennium Development Goal (MDG) targeted at improving
      maternal health. In this regard, Ethiopia has shown substantial progresses in the
      past two decades. Nonetheless, these impressive gains are unevenly distributed
      among Ethiopian women with different socio-economic characteristics. This study
      aimed at investigating levels and trends of skilled delivery service, and wealth
      and education related inequalities from 2000 to 16. METHODS: Longitudinal data
      analysis was conducted on Ethiopian Demographic and Health Survey (EDHS) data of
      2000, 2005, 2011 and 2016. The outcome variable was skilled delivery, while data
      on economic status and education level were used as dimensions of inequality.
      Rate Ratio (RR) and Rate Difference (RD) inequality measures were applied. STATA
      for windows version 10.1 statistical software was utilized for data analysis and
      presentation. The strength of association of inequality dimensions with the
      outcome variable was assessed using a 95% confidence interval. RESULTS: From
      total deliveries, 5.62%, 6.3%, 10.8% and 28% of them were attended by skilled
      birth attendant in 2000, 2005, 2011 and 2016 respectively. In the most recent
      survey (EDHS 2016), proportion of births attended by skilled birth attendance
      among women who completed secondary and above education was about 5.42 [95% CI
      (4.53, 6.09)] times more when compared to women with no formal education.
      Proportion of births attended by skilled birth attendance among women in the
      richest quintile was about 5.11 [95% CI (3.98, 6.12)] times higher than that of
      women in the poorest quintile. Moreover, gap of inequality on receiving skilled
      delivery service has increased substantially from 24.2 (2000) to 53.8 (2016)
      percentage points between women in the richest and poorest quintiles; and from
      44.9 (2000) to 76.0 (2016) percentage points between women who completed
      secondary and above education and women with no formal education. CONCLUSIONS:
      Skilled birth attendance remained low and virtually unchanged during the period
      2000-2011, but increased substantially in 2016. Gap on wealth and education
      related inequalities increased linearly during 2000-16. Most pronounced
      inequalities were observed in women's level of education revealing women with no
      formal education were the most underserved subgroups. Encouraging women in
      education and economic development programs should be strengthened as part of the
      effort to attain Universal Health Coverage (UHC) of Sustainable Development Goals
      (SDGs) in Ethiopia.

PMID- 28511658
TI  - Global Kalman filter approaches to estimate absolute angles of lower limb
      segments.
AB  - BACKGROUND: In this paper we propose the use of global Kalman filters (KFs) to
      estimate absolute angles of lower limb segments. Standard approaches adopt KFs to
      improve the performance of inertial sensors based on individual link
      configurations. In consequence, for a multi-body system like a lower limb
      exoskeleton, the inertial measurements of one link (e.g., the shank) are not
      taken into account in other link angle estimations (e.g., foot). Global KF
      approaches, on the other hand, correlate the collective contribution of all
      signals from lower limb segments observed in the state-space model through the
      filtering process. We present a novel global KF (matricial global KF) relying
      only on inertial sensor data, and validate both this KF and a previously
      presented global KF (Markov Jump Linear Systems, MJLS-based KF), which fuses data
      from inertial sensors and encoders from an exoskeleton. We furthermore compare
      both methods to the commonly used local KF. RESULTS: The results indicate that
      the global KFs performed significantly better than the local KF, with an average
      root mean square error (RMSE) of respectively 0.942 degrees  for the MJLS-based
      KF, 1.167 degrees  for the matrical global KF, and 1.202 degrees  for the local
      KFs. Including the data from the exoskeleton encoders also resulted in a
      significant increase in performance. CONCLUSION: The results indicate that the
      current practice of using KFs based on local models is suboptimal. Both the
      presented KF based on inertial sensor data, as well our previously presented
      global approach fusing inertial sensor data with data from exoskeleton encoders,
      were superior to local KFs. We therefore recommend to use global KFs for gait
      analysis and exoskeleton control.

PMID- 28511659
TI  - Antiplasmodial activity of Indigofera spicata root extract against Plasmodium
      berghei infection in mice.
AB  - BACKGROUND: In addition to pharmacovigilance and pharmaco-economic concerns,
      resistance to anti-malarial medicines has been documented in all classes of anti
      malarials and this is further worsened by resistance to common insecticides by
      malaria vector, which is a major threat to malaria control. As a means of facing
      the challenges of searching for new anti-malarial agents, the current study
      focused on evaluation of anti-malarial activity of root extract of Indigofera
      spicata. METHODS: Chloroquine-sensitive rodent malaria parasite, Plasmodium
      berghei (ANKA strain) was used to infect the Swiss Albino mice in 4-day
      suppressive and curative models. The crude hydromethanolic root extract of I.
      spicata at 200, 400 and 600 mg/kg doses was administered to a group of five mice.
      Important parameters, such as level of parasitaemia, packed cell volume (PCV),
      survival time, and body weight were determined and the significance of the
      differences between mean values of the five groups was analysed by one-way ANOVA
      followed by post hoc Tukey's Multiple Comparison test. RESULTS: In both the
      suppressive and curative models, 400 and 600 mg/kg doses of the extract
      suppressed the level of parasitaemia significantly (p < 0.001) compared to the
      vehicle-treated groups, 34.93 and 53.42%, respectively. However, only the mice
      which were treated with the 600 mg/kg dose of the extract had significant
      difference in their mean survival time. In other parameters, namely PCV and mean
      body weight, there was no statistically significant difference between the
      extract-treated groups when compared to the negative control. CONCLUSIONS: This
      study revealed that the root extract of I. spicata possesses anti-malarial
      activity and necessitates further scientific validation.

PMID- 28511660
TI  - Simvastatin for patients with acute respiratory distress syndrome: long-term
      outcomes and cost-effectiveness from a randomised controlled trial.
AB  - BACKGROUND: Simvastatin therapy for patients with acute respiratory distress
      syndrome (ARDS) has been shown to be safe and associated with minimal adverse
      effects, but it does not improve clinical outcomes. The aim of this research was
      to report on mortality and cost-effectiveness of simvastatin in patients with
      ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a
      multicentre, double-blind, randomised controlled trial carried out in the UK and
      Ireland. Five hundred and forty intubated and mechanically ventilated patients
      with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a
      dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS:
      Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI)
      26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months,
      although this was not significant. Simvastatin was associated with statistically
      significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95%
      CI 0.002-0.127) compared to placebo. Simvastatin was also less costly
      (incremental total costs -L3601, 95% CI -8061 to 859). At a willingness-to-pay
      threshold of L20,000 per QALY, the probability of simvastatin being cost
      effective was 99%. Sensitivity analyses indicated that the results were robust to
      changes in methodological assumptions with the probability of cost-effectiveness
      never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective
      for the treatment of ARDS, being associated with both a significant QALY gain and
      a cost saving. There was no significant reduction in mortality at 12 months,
      TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.

PMID- 28511661
TI  - A preliminary investigation on the utility of temporal features of Force
      Myography in the two-class problem of grasp vs. no-grasp in the presence of upper
      extremity movements.
AB  - BACKGROUND: In upper-extremity stroke rehabilitation applications, the potential
      use of Force Myography (FMG) for detecting grasping is especially relevant, as
      the presence of grasping may be indicative of functional activity, which is a key
      goal of rehabilitation. To date, most FMG research has focused on the
      classification of the raw FMG signal (i.e. instantaneous FMG samples) in order to
      determine the state of the hand. However, given the temporal nature of force
      generation during grasping, the use of temporal feature extraction techniques may
      yield increased accuracy. In this study, the effectiveness of classifying
      temporal features of the FMG signal for the two-class grasp detection problem of
      "grasp" versus "no grasp" (i.e. no object in hand) was evaluated with ten healthy
      participants. The experimental protocol comprised grasp and move tasks, requiring
      the use of six different grasp types frequently used in daily living, in
      conjunction with arm and hand movements. Data corresponding to arm and hand
      movements without grasping were also included to evaluate robustness to false
      positives. The temporal features evaluated were mean absolute value (MAV), root
      mean squared (RMS), linear fit (LF), parabolic fit (PF), and autoregressive model
      (AR). Off-line classification performance of the five temporal features, with a
      0.5 s extraction window, were determined and compared to that of the raw FMG
      signal using area under the receiver operating curve (AUC). RESULTS: The raw FMG
      signal yielded AUC of 0.819 +/- 0.098. LF and PF resulted in the greatest
      increases in classification performance, and provided statistically significant
      increases in performance. The largest increase obtained was with PF, yielding AUC
      of 0.869 +/- 0.061, corresponding to a 6.1% relative increase over the raw FMG
      signal. Despite the additional fitting term provided by PF, classification
      performance did not significantly improve with PF when compared to LF.
      CONCLUSIONS: The results obtained indicate that temporal feature extraction
      techniques that derive models of the data within the window may yield modest
      improvements in FMG based grasp detection performance. In future studies, the use
      of model-based temporal features should be evaluated with FMG data from
      individuals with stroke, who might ultimately benefit from this technology.

PMID- 28511662
TI  - Response to the Letter to the Editor by Eberhard et al.
AB  - In a Letter to the Editor, Eberhard et al. question the validity of our model of
      skin snip sensitivity and argue against the use of skin snips to evaluate
      onchocerciasis elimination by mass drug administration. Here we discuss their
      arguments and compare model predictions with observed data to assess the validity
      of our model.

PMID- 28511665
TI  - Clone temporal centrality measures for incomplete sequences of graph snapshots.
AB  - BACKGROUND: Different phenomena like the spread of a disease, social interactions
      or the biological relation between genes can be thought of as dynamic networks.
      These can be represented as a sequence of static graphs (so called graph
      snapshots). Based on this graph sequences, classical vertex centrality measures
      like closeness and betweenness centrality have been extended to quantify the
      importance of single vertices within a dynamic network. An implicit assumption
      for the calculation of temporal centrality measures is that the graph sequence
      contains all information about the network dynamics over time. This assumption is
      unlikely to be justified in many real world applications due to limited access to
      fully observed network data. Incompletely observed graph sequences lack important
      information about duration or existence of edges and may result in biased
      temporal centrality values. RESULTS: To account for this incompleteness, we
      introduce the idea of extending original temporal centrality metrics by cloning
      graphs of an incomplete graph sequence. Focusing on temporal betweenness
      centrality as an example, we show for different simulated scenarios of incomplete
      graph sequences that our approach improves the accuracy of detecting important
      vertices in dynamic networks compared to the original methods. An age-related
      gene expression data set from the human brain illustrates the new measures.
      Additional results for the temporal closeness centrality based on cloned
      snapshots support our findings. We further introduce a new algorithm called REN
      to calculate temporal centrality measures. Its computational effort is linear in
      the number of snapshots and benefits from sparse or very dense dynamic networks.
      CONCLUSIONS: We suggest to use clone temporal centrality measures in incomplete
      graph sequences settings. Compared to approaches that do not compensate for
      incompleteness our approach will improve the detection rate of important
      vertices. The proposed REN algorithm allows to calculate (clone) temporal
      centrality measures even for long snapshot sequences.

PMID- 28511666
TI  - Barriers and facilitators of access to maternal services for women with
      disabilities: scoping review protocol.
AB  - BACKGROUND: The Sustainable Development Goals (SDGs) emphasises the increasing
      equitable coverage of quality health care and provision of integrated services as
      means of reducing maternal mortality. Despite so much effort being placed on
      improved access to maternity health care, studies show that women with
      disabilities are being systemically excluded from the mainstream maternal health
      services. The proposed scoping review aims to map literature on the barriers and
      facilitators of access to maternal services for women with disabilities. METHODS
      AND ANALYSIS: The search strategy for this scoping review study will involve
      electronic databases including Pubmed, MEDLINE via EBSCOhost, CINAHL Plus with
      full text via EBSCOhost, Africa-Wide Info via EBSCOhost, JSTOR and Proquest
      Health and Medical Complete. Articles will also be searched through the "Cited
      by" search as well as citations included in the reference lists of included
      articles. A two-stage mapping strategy would be conducted. Stage 1 would be to
      screen studies through examining their titles. Furthermore, we will screen
      abstracts of the identified studies descriptively and by focus and method as
      stipulated by the inclusion and exclusion criteria. In stage 2, we will extract
      data from the included studies. A parallel screening and data extraction will be
      undertaken by two reviewers. We will access the quality of the included studies
      using the mixed methods appraisal tool (MMAT). We will use NVIVO version 10 to
      extract the relevant outcomes and thematic analysis of the studies. DISCUSSION:
      We anticipate to find relevant studies reporting evidence on the barriers and
      facilitators of access to maternal health services in Sub-Saharan Africa. The
      evidence obtained from the included studies when summarised will help guide
      future research. The study findings will be disseminated electronically and in
      print. In addition, it will be presented at conferences related to sexual
      reproductive health, maternal health care and reproductive health.

PMID- 28511663
TI  - Basic fibroblast growth factor reduces scar by inhibiting the differentiation of
      epidermal stem cells to myofibroblasts via the Notch1/Jagged1 pathway.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) plays an important role in
      promoting wound healing and reducing scar, but the possible molecular mechanisms
      are still unclear. Our previous studies have found that activating the
      Notch1/Jagged1 pathway can inhibit the differentiation of epidermal stem cells
      (ESCs) to myofibroblasts (MFB). Herein, we document that bFGF reduces scar by
      inhibiting the differentiation of ESCs to MFB via activating the Notch1/Jagged1
      pathway. METHODS: In in-vitro study, ESCs were isolated from 10 neonatal SD rats
      (1-3 days old), cultured in keratinocyte serum-free medium, and divided into six
      groups: bFGF group, bFGF + SU5402 group, bFGF + DAPT group, siJagged1 group, bFGF
      + siJagged1 group, and control group. Jagged1 of the ESCs in the siJagged1 group
      and bFGF + siJagged1 group was knocked down by small-interfering RNA
      transfection. Expression of ESC markers (CK15/CK10), MFB markers (alpha-SMA,
      Collagen I, Collagen III), and Notch1/Jagged1 components (Jagged1, Notch1, Hes1)
      was detected by FCM, qRT-PCR, and western blot analysis to study the
      relationships of bFGF, ESCs, and Notch1/Jagged1 pathway. In in-vivo study, the
      wound healing time and scar hyperplasia were observed on rabbit ear scar models.
      The quality of wound healing was estimated by hematoxylin and eosin staining and
      Masson staining. Expression of ESC markers, MFB markers and Notch1/Jagged1
      components was elucidated by immunohistochemistry, immunofluorescence, and
      western blot analysis. RESULTS: The in-vitro study showed that bFGF could
      significantly upregulate the expression of ESC markers and Notch1/Jagged1
      components, while downregulating the expression of MFB markers at the same time.
      However, these effects could be obviously decreased when we knocked down Jagged1
      or added DAPT. Similarly, in in-vivo study, bFGF also exhibited its functions in
      inhibiting the differentiation of rabbit ESCs to MFB by activating the
      Notch1/Jagged1 pathway, which improved the wound healing quality and alleviated
      scar significantly. CONCLUSION: These results provide evidence that bFGF can
      reduce scar by inhibiting the differentiation of ESCs to MFB via the
      Notch1/Jagged1 pathway, and present a new promising potential direction for the
      treatment of scar.

PMID- 28511664
TI  - Yields and chondrogenic potential of primary synovial mesenchymal stem cells are
      comparable between rheumatoid arthritis and osteoarthritis patients.
AB  - BACKGROUND: Mesenchymal stem cells derived from the synovial membrane (synovial
      MSCs) are a candidate cell source for regenerative medicine of cartilage and
      menisci due to their high chondrogenic ability. Regenerative medicine can be
      expected for RA patients with the inflammation well-controlled as well as OA
      patients and transplantation of synovial MSCs would also be a possible
      therapeutic treatment. Some properties of synovial MSCs vary dependent on the
      diseases patients have, and whether or not the pathological condition of RA
      affects the chondrogenesis of synovial MSCs remains controversial. The purpose of
      this study was to compare the properties of primary synovial MSCs between RA and
      OA patients. METHODS: Human synovial tissue was harvested during total knee
      arthroplasty from the knee joints of eight patients with RA and OA respectively.
      Synovial nucleated cells were cultured for 14 days. Total cell yields, surface
      markers, and differentiation potentials were analyzed for primary synovial MSCs.
      RESULTS: Nucleated cell number per 1 mg synovium was 8.4 +/- 3.9 thousand in RA
      and 8.0 +/- 0.9 thousand in OA. Total cell number after 14-day culture/1 mg
      synovium was 0.7 +/- 0.4 million in RA and 0.5 +/- 0.3 million in OA, showing no
      significant difference between in RA and OA. Cells after 14-day culture were
      mostly positive for CD44, CD73, CD90, CD105, negative for CD45 both in RA and OA.
      There was no significant difference for the cartilage pellet weight and sGAG
      content per pellet between in RA and OA. Both oil red O-positive colony rate and
      alizarin red-positive colony rate were similar in RA and OA. CONCLUSIONS: Yields,
      surface markers and chondrogenic potential of primary synovial MSCs in RA were
      comparable to those in OA. Synovium derived from RA patients can be the cell
      source of MSCs for cartilage and meniscus regeneration.

PMID- 28511667
TI  - Epidemiology of pertussis in Casablanca (Morocco): contribution of conventional
      and molecular diagnosis tools.
AB  - BACKGROUND: Pertussis, a vaccine preventable disease, is still responsible of
      significant morbidity and mortality around the world, mostly in newborns. The aim
      of the present study was (1) to introduce pertussis surveillance in the major
      pediatric hospital of Casablanca (2) to analyze the prevalence of pertussis among
      children under 14 years of age and their entourage in Casablanca, Morocco.
      METHODS: This is a prospective and non-case controlled study, including children
      suspected of Pertussis admitted at the Abderrahim Harouchi Pediatric Hospital in
      Casablanca, from January 2013 to June 2015. Nasopharyngeal samples were obtained
      for Bordetella spp. culture and Real time PCR detection (RT-PCR) with specific
      primers of Bordetella spp., B. pertussis, B. parapertussis and B. holmesii. The
      detection of Bordetella spp. was also performed in some household contacts of the
      children suspected of pertussis. RESULTS: During the 2.5-years period, a total of
      282 samples were collected from hospitalized children (156) and in some of their
      contacts (126). Among 156 samples from the children (from whom 57% were under 2
      month of age), Bordetella DNA was detected in 61% (96/156) by RT-PCR. Among these
      positive samples, 91.7% (88/96) corresponded to B. pertussis DNA. Furthermore, in
      39.5% (38/96) of the Bordetella positive samples, B. holmesii DNA was also
      detected. B. parapertussis DNA was detected in only one sample (1/156). Out of
      the 156 samples collected from the hospitalized children, only 48 were tested by
      culture, and 4 B. pertussis were isolated (8.3%). Among the 126 samples from the
      contacts of the children, mostly mothers (115 cases), Bordetella DNA was detected
      in 47% (59/126), 90% (53/59) being B. pertussis DNA. Moreover, B. holmesii DNA
      was also detected in 18.6% (11/59) of the Bordetella positive samples, and
      coexistence of B. pertussis and B. holmesii DNA in 36.5% (35/96). Two B.
      pertussis were isolated by culture performed on 43 samples of the contacts of the
      children (4.6%). CONCLUSIONS: This study highlights the circulation of B.
      pertussis but also of B. holmesii in Casablanca-Morocco with a high proportion of
      co-infections B. holmesii/B. pertussis in infants and their mothers, indicate
      that infection of non-vaccinated infants could be more associated with young
      parents. Moreover, the RT- PCR provides a sensitive and specific diagnosis of B.
      pertussis infections and distinguishes it from other Bordetella species, and is
      therefore suitable for implementation in the diagnostic laboratory.

PMID- 28511668
TI  - Structural similarities and functional differences clarify evolutionary
      relationships between tRNA healing enzymes and the myelin enzyme CNPase.
AB  - BACKGROUND: Eukaryotic tRNA splicing is an essential process in the
      transformation of a primary tRNA transcript into a mature functional tRNA
      molecule. 5'-phosphate ligation involves two steps: a healing reaction catalyzed
      by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase
      (CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that
      catalyze tRNA healing in yeast and higher eukaryotes are homologous to the
      members of the 2H phosphoesterase superfamily, in particular to the vertebrate
      myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). RESULTS: We
      employed different biophysical and biochemical methods to elucidate the overall
      structural and functional features of the tRNA healing enzymes yeast Trl1
      PNK/CPDase and lancelet PNK/CPDase and compared them with vertebrate CNPase. The
      yeast and the lancelet enzymes have cyclic phosphodiesterase and polynucleotide
      kinase activity, while vertebrate CNPase lacks PNK activity. In addition, we also
      show that the healing enzymes are structurally similar to the vertebrate CNPase
      by applying synchrotron radiation circular dichroism spectroscopy and small-angle
      X-ray scattering. CONCLUSIONS: We provide a structural analysis of the tRNA
      healing enzyme PNK and CPDase domains together. Our results support evolution of
      vertebrate CNPase from tRNA healing enzymes with a loss of function at its N
      terminal PNK-like domain.

PMID- 28511669
TI  - Fasting levels of growth hormone are associated with carotid intima media
      thickness but are not affected by fluvastatin treatment.
AB  - BACKGROUND: Growth hormone (GH) has been linked to cardiovascular disease but the
      exact mechanism of this association is still unclear. We here test if the fasting
      levels of GH are cross-sectionally associated with carotid intima media thickness
      (IMT) and whether treatment with fluvastatin affects the fasting level of GH.
      METHODS: We examined the association between GH and IMT in 4425 individuals (aged
      46-68 years) included in the baseline examination (1991-1994) of the Malmo Diet
      and Cancer cardiovascular cohort (MDC-CC). From that cohort we then studied 472
      individuals (aged 50-70 years) who also participated (1994-1999) in the beta
      Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS), a randomized,
      double blind, placebo-controlled, single-center clinical trial. Using
      multivariate linear regression models we related the change in GH-levels at 12
      months compared with baseline to treatment with 40 mg fluvastatin once daily.
      RESULTS: In MDC-CC fasting values of GH exhibited a positive cross-sectional
      relation to the IMT at the carotid bulb independent of traditional cardiovascular
      risk factors (p = 0.002). In a gender-stratified analysis the correlation were
      significant for males (p = 0.005), but not for females (p = 0.09). Treatment with
      fluvastatin was associated with a minor reduction in the fasting levels of hs-GH
      in males (p = 0.05) and a minor rise in the same levels among females (p = 0.05).
      CONCLUSIONS: We here demonstrate that higher fasting levels of GH are associated
      with thicker IMT in the carotid bulb in males. Treatment with fluvastatin for 12
      months only had a minor, and probably not clinically relevant, effect on the
      fasting levels of hs-GH.

PMID- 28511671
TI  - Erratum to: Investigation of the association between the TCF7L2 rs7903146 (C/T)
      gene polymorphism and obesity in a Cameroonian population: a pilot study.

PMID- 28511670
TI  - Onco-testicular sperm extraction (onco-TESE) for bilateral testicular tumors: two
      case reports.
AB  - BACKGROUND: Most patients with testicular cancer are infertile; thus, the
      preservation of the sperm after surgery is an important factor to consider. We
      report two cases of bilateral testicular cancer in patients who underwent
      bilateral higher orchiectomy and simultaneous testicular sperm extraction. CASE
      PRESENTATION: Two Asian-Japanese men were referred to our hospital with bilateral
      testicular tumors. Both of the patients were preoperatively diagnosed with
      azoospermia and requested testicular sperm extraction at the time of higher
      orchiectomy. In one patient, sperm was successfully harvested and then frozen. In
      the other patient, sperm could not be retrieved from the patient's testis. In
      both patients, the pathological diagnosis was seminoma. Testicular tumors often
      occur in patients of reproductive age. The preservation of sperm before
      chemotherapy or bilateral orchiectomy is necessary for patients with testicular
      tumors who wish to be fathers. CONCLUSIONS: Onco-testicular sperm extraction
      might be an option for patients with testicular cancer and azoospermia or severe
      oligospermia.

PMID- 28511672
TI  - CrMAPK3 regulates the expression of iron-deficiency-responsive genes in
      Chlamydomonas reinhardtii.
AB  - BACKGROUND: Under iron-deficient conditions, Chlamydomonas exhibits high affinity
      for iron absorption. Nevertheless, the response, transmission, and regulation of
      downstream gene expression in algae cells have not to be investigated.
      Considering that the MAPK pathway is essential for abiotic stress responses, we
      determined whether this pathway is involved in iron deficiency signal
      transduction in Chlamydomonas. RESULTS: Arabidopsis MAPK gene sequences were used
      as entry data to search for homologous genes in Chlamydomonas reinhardtii genome
      database to investigate the functions of mitogen-activated protein kinase (MAPK)
      gene family in C. reinhardtii under iron-free conditions. Results revealed 16 C.
      reinhardtii MAPK genes labeled CrMAPK2-CrMAPK17 with TXY conserved domains and
      low homology to MAPK in yeast, Arabidopsis, and humans. The expression levels of
      these genes were then analyzed through qRT-PCR and exposure to high salt (150 mM
      NaCl), low nitrogen, or iron-free conditions. The expression levels of these
      genes were also subjected to adverse stress conditions. The mRNA levels of
      CrMAPK2, CrMAPK3, CrMAPK4, CrMAPK5, CrMAPK6, CrMAPK8, CrMAPK9, and CrMAPK11 were
      remarkably upregulated under iron-deficient stress. The increase in CrMAPK3
      expression was 43-fold greater than that in the control. An RNA interference
      vector was constructed and transformed into C. reinhardtii 2A38, an algal strain
      with an exogenous FOX1:ARS chimeric gene, to silence CrMAPK3. After this gene was
      silenced, the mRNA levels and ARS activities of FOX1:ARS chimeric gene and
      endogenous CrFOX1 were decreased. The mRNA levels of iron-responsive genes, such
      as CrNRAMP2, CrATX1, CrFTR1, and CrFEA1, were also remarkably reduced.
      CONCLUSION: CrMAPK3 regulates the expression of iron-deficiency-responsive genes
      in C. reinhardtii.

PMID- 28511674
TI  - Predictors of fifty days in-hospital mortality in patients with culture negative
      neutrocytic ascites.
AB  - BACKGROUND: Culture negative neutrocytic ascites is a variant of spontaneous
      bacterial peritonitis. But there are conflicting reports regarding the mortality
      associated with culture negativeneutrocytic ascites. Therefore we aim to
      determine the predictors of mortality associated with culture negativeneutrocytic
      ascites in a larger sample population. METHODS: We analysed 170 patients
      consecutively admitted to intensive care unit with diagnosis of culture negative
      neutrocytic ascites. The clinical, laboratory parameters, etiology of liver
      cirrhosis was determined along with the scores like model for end stage liver
      disease, child turcotte pugh were recorded. RESULTS: The 50 day in-hospital
      mortality rate in culture negative neutrocytic ascites was 39.41% (n = 67). In
      univariate analysis, means of parameters like total leucocyte count, urea,
      bilirubin, alanine transaminase, aspartate transaminase, international normalized
      ratio, acute kidney injury, septic shock, hepatic encephalopathy and model for
      end stage liver disease were significantly different among survived and those who
      died (P value <=0.05). Cox proportional regression model showed the hazard ratio
      (HR) of acute kidney injury was 2.212 (95% CI: 1.334-3.667), septic shock (HR =
      1.895, 95% CI: 1.081-3.323) and model for end stage liver disease (HR = 1.054,
      95% CI: 1.020-1.090). Receiver operating characteristics curve showed aspartate
      aminotransferase (AST) had highest area under the curve 0.761 (95% CI: 0.625
      0.785). CONCLUSION: Patients with culture negative neutrocytic ascites have a
      mortality rate comparable to spontaneous bacterial peritonitis. aspartate
      aminotransferase, alanine aminotransferase (ALT), acute kidney injury (AKI),
      model for end stage liver disease (MELD) and septic shock are the independent
      predictors of 50 days in-hospital mortality in culture negative neutrocytic
      ascites.

PMID- 28511673
TI  - Long-term safety and efficacy of vismodegib in patients with advanced basal cell
      carcinoma: final update of the pivotal ERIVANCE BCC study.
AB  - BACKGROUND: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the
      first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed
      objective response rates (ORRs) by independent review facility (IRF) of 30% and
      43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC),
      respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC).
      Herein, we present long-term safety and final investigator-assessed efficacy
      results in patients with mBCC or laBCC. METHODS: One hundred four patients with
      measurable advanced BCC received oral vismodegib 150 mg once daily until disease
      progression or intolerable toxicity. The primary end point was IRF-assessed ORR.
      Secondary end points included ORR, duration of response (DOR), progression-free
      survival, overall survival (OS), and safety. RESULTS: At data cutoff (39 months
      after completion of accrual), 8 patients were receiving the study drug (69
      patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC
      group (all partial responses) and 60.3% in the laBCC group (20 patients had
      complete response and 18 patients had partial response). ORRs were comparable
      across patient subgroups, including aggressive histologic subtypes (eg,
      infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC).
      Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC
      cohort. Adverse events remained consistent with clinical experience. Thirty-three
      deaths (31.7%) were reported; none were related to vismodegib. CONCLUSIONS: This
      long-term update of the ERIVANCE BCC trial demonstrated durability of response,
      efficacy across patient subgroups, and manageable long-term safety of vismodegib
      in patients with advanced BCC. TRIAL REGISTRATION: This study was registered
      prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.

PMID- 28511676
TI  - Physical therapists and importance of work participation in patients with
      musculoskeletal disorders: a focus group study.
AB  - BACKGROUND: Musculoskeletal disorders are a major health problem resulting in
      negative effects on wellbeing and substantial costs to society. Work
      participation is associated with positive benefits for both mental and physical
      health. Potentially, generalist physical therapists (GPTs) can play an important
      role in reducing absenteeism, presenteeism and associated costs in patients with
      musculoskeletal disorders. However, work participation is often insufficiently
      addressed within generalist physical therapy practice (GPTP). Therefore, this
      study evaluates whether GPTs take work participation into account as a
      determining factor in patients with musculoskeletal disorders, and how this might
      be improved. METHODS: This qualitative study consisted of seven focus groups
      involving 30 participants: 21 GPTs and 9 occupational physical therapists (OPTs).
      Based on an interview guide, participants were asked how they integrate work
      participation within their practice, how they collaborate with other
      professionals, and how GPTs can improve integration of the patient's work within
      their practice. RESULTS: Although participants recognized the importance of work
      participation, they mentioned that the integration of this item in their GPTP
      could be improved. Generally, GPTs place insufficient priority on work
      participation. Moreover, there is a lack of cooperation between the generalist
      physical therapist and (other) occupational healthcare providers (including
      OPTs), and the borderlines/differences between generalist physcial therapy and
      occupational health physcial therapy were sometimes unclear. GPTs showed a lack
      of knowledge and a need for additional information about several important work
      related factors (e.g. work content, physical and psychosocial working conditions,
      terms of employment). CONCLUSIONS: Although a patient's work is important, GPTs
      take insufficient account of work participation as a determining factor in the
      treatment of patients with musculoskeletal disorders. GPTs often lack specific
      knowledge about work-related factors, and there is insufficient cooperation
      between OPTs and other occupational healthcare providers. The integration of work
      participation within GPTP, and the cooperation between GPTs and other
      occupational healthcare providers, show room for improvement.

PMID- 28511675
TI  - Comparing adult renal stem cell identification, characterization and
      applications.
AB  - Despite growing interest and effort, a consensus has yet to be reached in regards
      to the identification of adult renal stem cells. Organ complexity and low
      turnover of renal cells has made stem cell identification difficult and lead to
      the investigation of multiple possible populations. In this review, we summarize
      the work that has been done toward finding and characterizing an adult renal stem
      cell population. In addition to giving a general overview of what has been done,
      we aim to highlight the variation in methods and outcomes. The methods used to
      locate potential stem cell populations can vary widely, but even within the
      relatively standard practice of BrdU labeling of slowly dividing cells, there are
      significant differences in protocols and results. Additional diversity exists in
      cell marker profiles and apparent differentiation potential seen in potential
      stem cell sources. Cataloging the variety of methods and outcomes seen so far may
      help to streamline future investigation and stear the field toward consensus. But
      even without firmly defined populations, the application of renal stem cells
      holds tantalizing potential. Populations of highly proliferative, multipotent
      cells of renal origin show the ability to engraft in injured kidneys, mitigate
      functional loss and occasionally show the ability to generate nephrons de novo.
      The progress toward regenerative medicine applications is also summarized.

PMID- 28511677
TI  - A strategy to improve phasing of whole-genome sequenced individuals through
      integration of familial information from dense genotype panels.
AB  - BACKGROUND: Haplotype reconstruction (phasing) is an essential step in many
      applications, including imputation and genomic selection. The best phasing
      methods rely on both familial and linkage disequilibrium (LD) information. With
      whole-genome sequence (WGS) data, relatively small samples of reference
      individuals are generally sequenced due to prohibitive sequencing costs, thus
      only a limited amount of familial information is available. However, reference
      individuals have many relatives that have been genotyped (at lower density). The
      goal of our study was to improve phasing of WGS data by integrating familial
      information from haplotypes that were obtained from a larger genotyped dataset
      and to quantify its impact on imputation accuracy. RESULTS: Aligning a pre-phased
      WGS panel [~5 million single nucleotide polymorphisms (SNPs)], which is based on
      LD information only, to a 50k SNP array that is phased with both LD and familial
      information (called scaffold) resulted in correctly assigning parental origin for
      99.62% of the WGS SNPs, their phase being determined unambiguously based on
      parental genotypes. Without using the 50k haplotypes as scaffold, that value
      dropped as expected to 50%. Correctly phased segments were on average longer
      after alignment to the genotype phase while the number of switches decreased
      slightly. Most of the incorrectly assigned segments, and subsequent switches,
      were due to singleton errors. Imputation from 50k SNP array to WGS data with
      improved phasing had a marginal impact on imputation accuracy (measured as r 2),
      i.e. on average, 90.47% with traditional techniques versus 90.65% with pre
      phasing integrating familial information. Differences were larger for SNPs
      located in chromosome ends and rare variants. Using a denser WGS panel (~13
      millions SNPs) that was obtained with traditional variant filtering rules, we
      found similar results although performances of both phasing and imputation
      accuracy were lower. CONCLUSIONS: We present a phasing strategy for WGS data,
      which indirectly integrates familial information by aligning WGS haplotypes that
      are pre-phased with LD information only on haplotypes obtained with genotyping
      data, with both LD and familial information and on a much larger population. This
      strategy results in very few mismatches with the phase obtained by Mendelian
      segregation rules. Finally, we propose a strategy to further improve phasing
      accuracy based on haplotype clusters obtained with genotyping data.

PMID- 28511678
TI  - Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17).
      part 1: development and content validity.
AB  - BACKGROUND: Fibromyalgia (FM), a disorder characterized by chronic widespread
      pain and tenderness, affects greater than five million individuals in the United
      States alone. Patients experience multiple symptoms in addition to pain, and
      among them, fatigue is one of the most bothersome and disabling. There is a
      growing body of literature suggesting that fatigue is a multidimensional concept.
      Currently, to our knowledge, no multidimensional Patient Reported Outcome (PRO)
      measure of FM-related fatigue meets Food and Drug Administration (FDA)
      requirements to support a product label claim. Therefore, the objective of this
      research was to evaluate qualitative and quantitative data previously gathered to
      inform the development of a comprehensive, multidimensional, PRO measure to
      assess FM-related fatigue in FM clinical trials. METHODS: Existing qualitative
      and quantitative data from three previously conducted studies in patients with FM
      were reviewed to inform the initial development of a multidimensional PRO measure
      of FM-related fatigue: 1) a concept elicitation study involving in-depth, open
      ended interviews with patients with FM in the United States (US) (N = 20),
      Germany (N = 10), and France (N = 10); 2) a cognitive debriefing and pilot study
      of a preliminary pool of 23 items (N = 20 US patients with FM); and 3) a
      methodology study that explored initial psychometrics of the item pool (N = 145
      US patients with FM). RESULTS: Five domains were identified that intend to
      capture the broad experience of FM-related fatigue reported in the qualitative
      research: the Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue,
      Motivation, and Impact on Function. Seventeen of the original pool of 23 items
      were selected to best capture these five dimensions. These 17 items formed the
      basis of a newly developed multidimensional PRO measure to assess FM-related
      fatigue in clinical trials: the Multidimensional Daily Diary of Fatigue
      Fibromyalgia-17 (MDF-Fibro-17). CONCLUSION: Qualitative analysis, and preliminary
      quantitative item level data, confirmed that FM-related fatigue is
      multidimensional and provided strong support for the content validity of the MDF
      Fibro-17. The next stage was to quantitatively evaluate the measure to confirm
      the factor structure, psychometric properties, sensitivity to change, and
      meaningful change. This has been conducted and is being reported separately.

PMID- 28511679
TI  - Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus
      niruri L. (Euphorbiaceae) leaves in experimental rats.
AB  - BACKGROUND: The medicinal plants signify a massive basin of potential
      phytoconstituents that could be valuable as a substitute to allopathic drugs or
      considered as an analogue in drug development. Phyllanthus niruri L.
      (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and
      inflammation. In this project we investigated the methanolic extract of leaves of
      Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. METHODS: The
      anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was
      evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20
      mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats.
      Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left
      hind paw. Paw tissues from the different groups were examined for inflammatory
      cell infiltration. On the other hand, antiulcer activity of methanolic extract of
      P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined
      against ethanol-acid induced gastric mucosal injury in the Swiss albino rats -
      keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the
      stomachs were macroscopically examined to identify hemorrhagic lesions in the
      glandular mucosa. RESULTS: P. niruri significantly (p < 0.01) decreased
      carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and
      69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were
      further supported by the histological study. The methanolic extract also
      disclosed good protective effect against ethanol-acid induced gastric mucosal
      injury in the rats. Administration of the extract's doses (100, 200 and 400
      mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid
      induced gastric erosion in all the experimental groups when compared to the
      control. The methanolic extract at the higher dose (400 mg/kg) resulted in better
      inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20
      mg/kg). Histological studies of the gastric wall revealed that toxic control rats
      revealed mucosal degeneration, ulceration and migration of numerous inflammatory
      cells throughout the section. On the other hand, MEPN treatment groups showed
      significant regeneration of mucosal layer and significantly prevented the
      formation of hemorrhage and edema. CONCLUSIONS: The investigation suggests that
      methanolic extract of P. niruri leaf possess anti-inflammatory activity and
      promotes ulcer protection as ascertained by regeneration of mucosal layer and
      substantial prevention of the formation of hemorrhage and edema.

PMID- 28511680
TI  - Cohort profile: seek, test, treat and retain United States criminal justice
      cohort.
AB  - BACKGROUND: The STTR treatment cascade provides a framework for research aimed at
      improving the delivery of services, care and outcomes of PLWH. The development of
      effective approaches to increase HIV diagnoses and engage PLWH in subsequent
      steps of the treatment cascade could lead to earlier and sustained ART treatment
      resulting in viral suppression. There is an unmet need for research applying the
      treatment cascade to improve outcomes for those with criminal justice
      involvement. METHODS: The Seek, Test, Treat, and Retain (STTR) criminal justice
      (CJ) cohort combines data from 11 studies across the HIV treatment cascade that
      focused on persons involved in the criminal justice system, often but not
      exclusively for reasons related to substance use. The studies were conducted in a
      variety of CJ settings and collected information across 11 pre-selected domains:
      demographic characteristics, CJ involvement, HIV risk behaviors, HIV and/or
      Hepatitis C infections, laboratory measures of CD4 T-cell count (CD4) and HIV RNA
      viral load (VL), mental illness, health related quality of life (QoL),
      socioeconomic status, health care access, substance use, and social support.
      RESULTS: The STTR CJ cohort includes data on 11,070 individuals with and without
      HIV infection who range in age from 18 to 77 years, with a median age at baseline
      of 37 years. The cohort reflects racial, ethnic and gender distributions in the
      U.S. CJ system, and 64% of participants are African-American, 12% are Hispanic
      and 83% are men. Cohort members reported a wide range of HIV risk behaviors
      including history of injection drug use and, among those who reported on pre
      incarceration sexual behaviors, the prevalence of unprotected sexual intercourse
      ranged across studies from 4% to 79%. Across all studies, 53% percent of the STTR
      CJ cohort reported recent polysubstance use. CONCLUSIONS: The STTR CJ cohort is
      comprised of participants from a wide range of CJ settings including jail,
      prison, and community supervision who report considerable diversity in their
      characteristics and behavioral practices. We have developed harmonized measures,
      where feasible, to improve the integration of these studies together to answer
      questions that cannot otherwise be addressed.

PMID- 28511681
TI  - Chromosome engineering of Escherichia coli for constitutive production of
      salvianic acid A.
AB  - BACKGROUND: Salvianic acid A (SAA), a valuable natural product from herbal plant
      Salvia miltiorrhiza, exhibits excellent antioxidant activities on food industries
      and efficacious therapeutic potential on cardiovascular diseases. Recently,
      production of SAA in engineered Escherichia coli was established via the
      artificial biosynthetic pathway of SAA on the multiple plasmids in our previous
      work. However, the plasmid-mediated system required to supplement expensive
      inducers and antibiotics during the fermentation process, restricting scale-up
      production of SAA. Microbial cell factory would be an attractive approach for
      constitutive production of SAA by chromosome engineering. RESULTS: The limited
      enzymatic reactions in SAA biosynthetic pathway from glucose were grouped into
      three modules, which were sequentially integrated into chromosome of engineered
      E. coli by lambda Red homologous recombination method. With starting strain E.
      coli BAK5, in which the ptsG, pykF, pykA, pheA and tyrR genes were previously
      deleted, chassis strain BAK11 was constructed for constitutive production of
      precursor L-tyrosine by replacing the 17.7-kb mao-paa cluster with module 1 (P
      lacUV5 -aroG fbr -tyrA fbr -aroE) and the lacI gene with module 2 (P trc -glk
      tktA-ppsA). The synthetic 5tacs promoter demonstrated the optimal strength to
      drive the expression of hpaBC-d-ldh Y52A in module 3, which then was inserted at
      the position between nupG and speC on the chromosome of strain BAK11. The final
      strain BKD13 produced 5.6 g/L of SAA by fed-batch fermentation in 60 h from
      glucose without any antibiotics and inducers supplemented. CONCLUSIONS: The
      plasmid-free and inducer-free strain for SAA production was developed by targeted
      integration of the constitutive expression of SAA biosynthetic genes into E. coli
      chromosome. Our work provides the industrial potential for constitutive
      production of SAA by the indel microbial cell factory and also sets an example of
      further producing other valuable natural and unnatural products.

PMID- 28511682
TI  - Inequities in coverage of smokefree space policies within the United States.
AB  - BACKGROUND: Previous studies have found extensive geographic and demographic
      differences in tobacco use. These differences have been found to be reduced by
      effective public policies, including banning smoking in public spaces. Smokefree
      indoor and outdoor spaces reduce secondhand smoke exposure and denormalize
      smoking. METHODS: We evaluated regional and demographic differences in the
      proportion of the population covered by smokefree policies enacted in the United
      States prior to 2014, for both adults and children. RESULTS: Significant
      differences in coverage were found by ethnicity, region, income, and education (p
      < 0.001). Smokefree policy coverage was lower for jurisdictions with higher
      proportions of poor households, households with no high school diploma and the
      Southeast region. Increased ethnic heterogeneity was found to be a significant
      predictor of coverage in indoor "public spaces generally", meaning that diversity
      is protective, with differential effect by region (p = 0.004) - which may relate
      to urbanicity. Children had a low level of protection in playgrounds and schools
      (~10% covered nationwide) - these spaces were found to be covered at lower rates
      than indoor spaces. CONCLUSIONS: Disparities in smokefree space policies have
      potential to exacerbate existing health inequities. A national increase in
      smokefree policies to protect children in playgrounds and schools is a crucial
      intervention to reduce such inequities.

PMID- 28511683
TI  - Acute coronary syndrome patients admitted to a cardiology vs non-cardiology
      service: variations in treatment & outcome.
AB  - BACKGROUND: Specialized cardiology services have contributed to reduced mortality
      in acute coronary syndromes (ACS).  We sought to evaluate the outcomes of ACS
      patients admitted to non-cardiology services in Southern Alberta. METHODS:
      Retrospective chart review performed on all troponin-positive patients in the
      Calgary Health Region identified those diagnosed with ACS by their attending
      team. Patients admitted to non-cardiology and cardiology services were compared,
      using linked data from the Alberta Provincial Project for Outcomes Assessment in
      Coronary Heart Disease (APPROACH) registry and the Strategic Clinical Network for
      Cardiovascular Health and Stroke. RESULTS: From January 1, 2007 to December 31,
      2008, 2105 ACS patients were identified, with 1636 (77.7%) admitted to cardiology
      and 469 (22.3%) to non-cardiology services. Patients admitted to non-cardiology
      services were older, had more comorbidities, and rarely received cardiology
      consultation (5.1%). Cardiac catheterization was underutilized (5.1% vs 86.4% in
      cardiology patients (p < 0.0001)), as was evidence-based pharmacotherapy (p <
      0.0001). Following adjustment for baseline comorbidities, 30-day through 4-year
      mortality was significantly higher on non-cardiology vs. cardiology services
      (49.1% vs. 11.0% respectively at 4-years, p < 0.0001). CONCLUSION: In a large ACS
      population in the Calgary Health Region, 25% were admitted to non-cardiology
      services. These patients had worse outcomes, despite adjustment for baseline risk
      factor differences. Although many patients were appropriately admitted to non
      cardiology services, the low use of investigations and secondary prevention
      medications may contribute to poorer patient outcome. Further research is
      required to identify process of care strategies to improve outcomes and lessen
      the burden of illness for patients and the health care system.

PMID- 28511684
TI  - Access to pediatric rheumatology care for Juvenile Idiopathic Arthritis in the
      United Arab Emirates.
AB  - BACKGROUND: This study looks at access to care for Juvenile Idiopathic Arthritis
      through pediatric rheumatology in the UAE, as an example of multi-ethnic society.
      METHODS: Patients with a diagnosis of Juvenile idiopathic arthritis were
      identified through the hospital electronic medical records system from January
      1st 2011 to December 31st 2014. All residents of the United Arab Emirates hold an
      Emirates identity card. We divided our patients into two groups: Emirati
      Emirates, who are native Emirati children and hold the Emirati nationality, as
      stated on their Emirates identity card, and who therefore have full,
      comprehensive access to free medical care; and non-Emirati-Emirates, who
      represent other nationalities, as stated on their Emirates identity card. The
      primary objective of this study is to look at access to care for Juvenile
      idiopathic arthritis through pediatric rheumatology in the two groups. The
      secondary objective is to look at the effect of having multiple types of
      healthcare insurance coverage on access to biologics. A retrospective review was
      carried out. RESULTS: Sixty-six patients with JIA identified: 33 Emirates and 33
      non-Emirates. For Emirates, the mean time from onset to first appointment with
      pediatric rheumatologist and diagnosis is 9 months (range: 1-48), and for non
      Emirates is 12.4 months (range: 1-96). Among the Emirates, 10 patients are
      currently on biologic with methotrexate. Among the non-Emirates, 15 are on
      biologic with methotrexate. Among the Emirates, 12 are currently in remission
      while on treatment, as are 10 non-Emirates. Regarding disability, one Emirati
      patient has blindness secondary to noncompliance while under previous treatment.
      One Non-Emirati developed joint deformities due to periods of noncompliance and
      no follow up. CONCLUSIONS: Delay in presentation to pediatric rheumatology has
      been identified as an important factor in our population, which is multi-cultural
      and multi-ethnic. Type of health care insurance cover did not affect number of
      patients getting biological therapy once patient seen in the pediatric
      rheumatology service.

PMID- 28511685
TI  - Respectful maternity care in Ethiopian public health facilities.
AB  - BACKGROUND: Disrespect and abuse of women during institutional childbirth
      services is one of the deterrents to utilization of maternity care services in
      Ethiopia and other low- and middle-income countries. This paper describes the
      prevalence of respectful maternity care (RMC) and mistreatment of women in
      hospitals and health centers, and identifies factors associated with occurrence
      of RMC and mistreatment of women during institutional labor and childbirth
      services. METHODS: This study had a cross sectional study design. Trained
      external observers assessed care provided to 240 women in 28 health centers and
      hospitals during labor and childbirth using structured observation checklists.
      The outcome variable, providers' RMC performance, was measured by nine behavioral
      descriptors. The outcome, any mistreatment, was measured by four items related to
      mistreatment of women: physical abuse, verbal abuse, absence of privacy during
      examination and abandonment. We present percentages of the nine RMC indicators,
      mean score of providers' RMC performance and the adjusted multilevel model
      regression coefficients to determine the association with a quality improvement
      program and other facility and provider characteristics. RESULTS: Women on
      average received 5.9 (66%) of the nine recommended RMC practices. Health centers
      demonstrated higher RMC performance than hospitals. At least one form of
      mistreatment of women was committed in 36% of the observations (38% in health
      centers and 32% in hospitals). Higher likelihood of performing high level of RMC
      was found among male vs. female providers ([Formula: see text], p = 0.012),
      midwives vs. other cadres ([Formula: see text], p = 0.002), facilities
      implementing a quality improvement approach, Standards-based Management and
      Recognition (SBM-R(c)) ([Formula: see text], p = 0.003), and among laboring women
      accompanied by a companion [Formula: see text], p = 0.003). No factor was
      associated with observed mistreatment of women. CONCLUSION: Quality improvement
      using SBM-R(c) and having a companion during labor and delivery were associated
      with RMC. Policy makers need to consider the role of quality improvement
      approaches and accommodating companions in promoting RMC. More research is needed
      to identify the reason for superior RMC performance of male providers over female
      providers and midwives compared to other professional cadre, as are longitudinal
      studies of quality improvement on RMC and mistreatment of women during labor and
      childbirth services in public health facilities.

PMID- 28511686
TI  - Intrathymic injection of hematopoietic progenitor cells establishes functional T
      cell development in a mouse model of severe combined immunodeficiency.
AB  - BACKGROUND: Even though hematopoietic stem cell transplantation can be curative
      in patients with severe combined immunodeficiency, there is a need for additional
      strategies boosting T cell immunity in individuals suffering from genetic
      disorders of lymphoid development. Here we show that image-guided intrathymic
      injection of hematopoietic stem and progenitor cells in NOD-scid IL2rgammanull
      mice is feasible and facilitates the generation of functional T cells conferring
      protective immunity. METHODS: Hematopoietic stem and progenitor cells were
      isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+,
      CD45.1+) and injected intravenously or intrathymically into both male and female,
      young or aged NOD-scid IL2rgammanull recipients. The in vivo fate of injected
      cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and
      spleen-derived T cell populations. In addition to T cell reconstitution, we
      evaluated mice for evidence of immune dysregulation based on diabetes development
      and graft-versus-host disease. T cell immunity following intrathymic injection of
      hematopoietic stem and progenitor cells in NOD-scid IL2rgammanull mice was
      assessed in a B cell lymphoma model. RESULTS: Despite the small size of the
      thymic remnant in NOD-scid IL2rgammanull mice, we were able to accomplish precise
      intrathymic delivery of hematopoietic stem and progenitor cells by ultrasound
      guided injection. Thymic reconstitution following intrathymic injection of
      healthy allogeneic hematopoietic cells was most effective in young male
      recipients, indicating that even in the setting of severe immunodeficiency, sex
      and age are important variables for thymic function. Allogeneic T cells generated
      in intrathymically injected NOD-scid IL2rgammanull mice displayed anti-lymphoma
      activity in vivo, but we found no evidence for severe auto/alloreactivity in T
      cell-producing NOD-scid IL2rgammanull mice, suggesting that immune dysregulation
      is not a major concern. CONCLUSIONS: Our findings suggest that intrathymic
      injection of donor hematopoietic stem and progenitor cells is a safe and
      effective strategy to establish protective T cell immunity in a mouse model of
      severe combined immunodeficiency.

PMID- 28511687
TI  - Polymeric micelles with dual thermal and reactive oxygen species (ROS)
      responsiveness for inflammatory cancer cell delivery.
AB  - BACKGROUND: The object of this study was to develop a thermally and reactive
      oxygen species-responsive nanocarrier system for cancer therapy. RESULTS: PPS
      PNIPAm block copolymer was designed and synthesised using a combination of living
      anionic ring-opening polymerization and atom transfer radical polymerization. The
      synthesized polymer formed micellar aggregates in water and demonstrated dual
      responsiveness towards temperature and oxidants. Using doxorubicin (DOX) as a
      model drug, encapsulation and in vitro release of the drug molecules in PPS
      PNIPAm nanocarriers confirmed the responsive release properties of such system.
      Cell uptake of the DOX loaded micelles was investigated with human breast cancer
      cell line (MCF-7). The results showed Dox-loaded micelles were able to be taken
      by the cells and mainly reside in the cytoplasma. In the stimulated cells with an
      elevated level of ROS, more released DOX was observed around the nuclei. In the
      cytotoxicity experiments, the Dox-loaded micelles demonstrated comparable
      efficacy to free DOX at higher concentrations, especially on ROS stimulated
      cells. CONCLUSIONS: These results demonstrated that PPS-PNIPAm nanocarriers
      possess the capability to respond two typical stimuli in inflammatory cells:
      temperature and oxidants and can be used in anticancer drug delivery.

PMID- 28511688
TI  - Predictors of adherence to micronutrient supplementation before and during
      pregnancy in Vietnam.
AB  - BACKGROUND: Poor adherence to micronutrient supplementation often limits the
      effectiveness of public health programs. While predictors of adherence to
      micronutrient supplementation during pregnancy are well documented, information
      on adherence to preconception supplements is scarce. The objective of this study
      was to describe the predictors of adherence to preconception and prenatal
      micronutrient supplementation among women participating in a randomized control
      trial in Vietnam. METHODS: Adherence data were collected prospectively from a
      double blind randomized controlled trial in rural Vietnam. Five thousand eleven
      women of reproductive age were randomized to receive preconception supplements
      for weekly consumption containing either: Folic Acid, Iron and Folic Acid (IFA),
      or Multiple Micronutrients. Women who became pregnant received prenatal IFA
      supplements for daily consumption through delivery. Village health workers
      visited participants' homes every two weeks to deliver supplements and record
      consumption and side effects. Multivariate logistic regression was used to assess
      individual, household, and programmatic predictors of supplement adherence.
      RESULTS: Adherence was high with 78 and 82% of the women consuming more than 80%
      of the preconception and prenatal supplements, respectively. Women of minority
      ethnicity (OR = 0.78 95% CI = 0.67, 0.91) and farmers (OR = 0.71 95% CI = 0.58,
      0.88) were less likely to consume >80% of the preconception supplements while
      socioeconomic status (SES) (OR = 2.71 highest vs. lowest quintile; 95% CI = 2.10,
      3.52) was positively associated with >80% adherence in the entire preconception
      sample with available information (n = 4417). Women in their first pregnancy had
      lower prenatal adherence compared to multiparous women. At the programmatic
      level, each village health worker visit was associated with higher odds of >80%
      adherence by 3-5% before pregnancy and 18% during pregnancy. CONCLUSIONS: Key
      determinants of adherence included SES, ethnicity, occupation (farmer) and parity
      which may be helpful for targeting women for counseling on supplement adherence.
      Increased contact with village health workers was positively associated with
      adherence to micronutrient supplementation both before conception and during
      pregnancy indicating the need for resources to support community outreach to
      women of reproductive age. TRIAL REGISTRATION: NCT01665378 . Registered on August
      12, 2012.

PMID- 28511689
TI  - Harnessing interactive technologies to improve health outcomes in juvenile
      idiopathic arthritis.
AB  - BACKGROUND: Children and adolescents with Juvenile Idiopathic Arthritis (JIA)
      typically have reduced physical activity level and impaired aerobic and anaerobic
      exercise capacity when compared to their non-JIA counterparts. Low intensity
      exercise regimens appear to be safe in children with JIA and may results in
      improvements in overall physical function. Poor adherence to paediatric
      rheumatology treatment may lead to negative clinical outcomes and possibly
      increased disease activity. This includes symptoms such as pain, fatigue, quality
      of life, longer term outcomes including joint damage, as well as increase of
      healthcare associated costs. Low adherence to medications such as methotrexate
      and biological-drugs remains a significant issue for paediatric rheumatologists,
      with alarming reports that less than half of the children with JIA are compliant
      to drug-therapy. MAIN BODY: The recent advances in interactive technology
      resulting in a variety of wearable user-friendly smart devices may become a key
      solution to address important questions in JIA clinical management. Fully
      understanding the impact that arthritis and treatment complications have upon
      individual children and their families has long been a challenge for clinicians.
      Modern interactive technologies can be customised and accessed directly in the
      hands or wrists of children with JIA. These secured networks could be accessible
      'live' at anytime and anywhere by the child, parents and clinicians.
      Multidisciplinary teams in paediatric rheumatology may benefit from adopting
      these technologies to better understand domains such as patient biological
      parameters, symptoms progression, adherence to drug-therapy, quality of life, and
      participation in physical activities. Most importantly the use of smart devices
      technologies may also facilitate more timely clinical decisions, improve self
      management and parents awareness in the progression of their child's disease.
      Paediatric rheumatology research could also benefit from the use of these smart
      devices, as they would allow real-time access to meaningful data to thoroughly
      understand the disease-patterns of JIA, such as pain and physical activity
      outcomes. Data collection that typically occurs once every 1 or 3 months in the
      clinical setting could instead be gathered every week, day, minute or virtually
      live online. Arguably, few limitations in wearing such interactive technologies
      still exist and require further developments. CONCLUSION: Finally, by embracing
      and adapting these new and now highly accessible interactive technologies,
      clinical management and research in paediatric rheumatology may be greatly
      advanced.

PMID- 28511690
TI  - Development of a clinical prediction algorithm for knee osteoarthritis structural
      progression in a cohort study: value of adding measurement of subchondral bone
      density.
AB  - BACKGROUND: Risk prediction algorithms increase understanding of which patients
      are at greatest risk of a harmful outcome. Our goal was to create a clinically
      useful prediction algorithm for structural progression of knee osteoarthritis
      (OA), using medial joint space loss as a proxy; and to quantify the benefit of
      including periarticular bone mineral density (BMD) in the algorithm. METHODS:
      Participants were from the Osteoarthritis Initiative (OAI) Progression Cohort,
      with X-ray readings of medial joint space at 36- and 48-month visits, and a 30-
      or 36-month medial-to-lateral tibial BMD ratio (M:L BMD ratio) value. Loss of
      medial joint space was the outcome and clinically available factors associated
      with OA progression were employed in the base prediction algorithm, with M:L BMD
      ratio added to an enhanced prediction algorithm. The benefit of adding M:L BMD
      ratio was evaluated by change in area under the ROC curve (AUC), net
      reclassification improvement (NRI), and integrated discrimination improvement
      (IDI). RESULTS: Five hundred thirty-three participants were included; 51 (14%)
      had medial joint space loss; 47% were female; the mean (SD) age was 64.6 (9.2)
      years and BMI was 29.6 (4.8) kg/m2. The base algorithm model included age, BMI,
      gender, recent injury, knee pain, and hand OA as predictors and had an AUC value
      of 0.65. The algorithm adding M:L BMD ratio had an AUC value of 0.73, and the
      AUC, NRI and IDI were all significantly improved (p <= 0.002). CONCLUSIONS: This
      clinical prediction algorithm predicts structural progression in individuals with
      OA using only clinically available predictors supplemented by the M:L BMD ratio,
      a biomarker that could be made available at clinical sites.

PMID- 28511691
TI  - Tomato root microbiota and Phytophthora parasitica-associated disease.
AB  - BACKGROUND: Interactions between pathogenic oomycetes and microbiota residing on
      the surface of the host plant root are unknown, despite being critical to
      inoculum constitution. The nature of these interactions was explored for the
      polyphagous and telluric species Phytophthora parasitica. RESULTS: Composition of
      the rhizospheric microbiota of Solanum lycopersicum was characterized using deep
      re-sequencing of 16S rRNA gene to analyze tomato roots either free of or partly
      covered with P. parasitica biofilm. Colonization of the host root surface by the
      oomycete was associated with a shift in microbial community involving a
      Bacteroidetes/Proteobacteria transition and Flavobacteriaceae as the most
      abundant family. Identification of members of the P. parasitica-associated
      microbiota interfering with biology and oomycete infection was carried out by
      screening for bacteria able to (i) grow on a P. parasitica extract-based medium
      (ii), exhibit in vitro probiotic or antibiotic activity towards the oomycete
      (iii), have an impact on the oomycete infection cycle in a tripartite interaction
      S. lycopersicum-P. parasitica-bacteria. One Pseudomonas phylotype was found to
      exacerbate disease symptoms in tomato plants. The lack of significant gene
      expression response of P. parasitica effectors to Pseudomonas suggested that the
      increase in plant susceptibility was not associated with an increase in
      virulence. Our results reveal that Pseudomonas spp. establishes commensal
      interactions with the oomycete. Bacteria preferentially colonize the surface of
      the biofilm rather than the roots, so that they can infect plant cells without
      any apparent infection of P. parasitica. CONCLUSIONS: The presence of the
      pathogenic oomycete P. parasitica in the tomato rhizosphere leads to a shift in
      the rhizospheric microbiota composition. It contributes to the habitat extension
      of Pseudomonas species mediated through a physical association between the
      oomycete and the bacteria.

PMID- 28511692
TI  - Vitamin D receptor activation reduces inflammatory cytokines and plasma MicroRNAs
      in moderate chronic kidney disease - a randomized trial.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major risk factor for
      cardiovascular disease (CVD), partly due to endothelial dysfunction and chronic
      inflammation. Vitamin D treatment in end stage renal disease is suggested to
      modulate the immune system and lead to improved outcomes. We and others have
      demonstrated that treatment with vitamin D or activated vitamin D analogues
      protects the endothelial function in less severe renal disease as well. Since the
      endothelial protection might be mediated by vitamin D effects on inflammation, we
      assessed levels of pro-inflammatory cytokines and micro RNAs (miRs) in patients
      with moderate CKD, treated with an active vitamin D analogue (paricalcitol).
      METHODS: Thirty-six patients with moderate CKD were randomized to 12 weeks
      treatment with placebo, 1 MUg, or 2 MUg paricalcitol daily. Cytokines were
      measured by Milliplex 26-plex. Total RNA was isolated from plasma and miRs were
      determined by quantitative reverse transcription PCR analysis. RESULTS: Selected
      pro-inflammatory cytokines decreased significantly following treatment, while no
      change was observed in the placebo group. The micro RNAs; miR 432-5p, miR 495-3p,
      and miR 576-5p were significantly downregulated in the active treated groups,
      compared to the placebo group. CONCLUSION: Paricalcitol treatment for 12 weeks in
      patients with moderate CKD reduces cytokines and micro RNAs involved in
      atherosclerosis and inflammation. The potentially protective role of vitamin D
      receptor activation in the inflammatory processes regarding the long-term
      outcomes in CKD patients warrants further studies. TRIAL REGISTRATION: SOLID
      study; NCT01204528 , April 27, 2010.

PMID- 28511693
TI  - Antagonistic action on NMDA/GluN2B mediated currents of two peptides that were
      conantokin-G structure-based designed.
AB  - BACKGROUND: The GluN2B subunit of the N-methyl-D-aspartate receptor (NMDAr)
      modulates many physiological processes including learning, memory, and pain.
      Excessive increase in NMDAr/GluN2B activity has been associated with various
      disorders such neuropathic pain and neuronal death following hypoxia. Thus there
      is an interest in identifying NMDAr antagonists that interact specifically with
      the GluN2B subunit. Recently based on structural analysis between the GluN2B
      subunit and conantokin-G, a toxin that interacts selectively with the GluN2B
      subunit, we designed various peptides that are predicted to act as NMDAr
      antagonists by interacting with the GluN2B subunit. In this study we tested this
      prediction for two of these peptides EAR16 and EAR18. RESULTS: The effects of
      EAR16 and EAR18 in NMDA-evoked currents were measured in cultured rat embryonic
      hippocampal neurons and in HEK-293 cells expressing recombinant NMDAr comprised
      of GluN1a-GluN2A or GluN1a-GluN2B subunits. In hippocampal neurons, EAR16 and
      EAR18 reduced the NMDA-evoked calcium currents in a dose-dependent and reversible
      manner with comparable IC50 (half maximal inhibitory concentration) values of 241
      and 176 uM, respectively. At 500 uM, EAR16 blocked more strongly the NMDA-evoked
      currents mediated by the GluN1a-GluN2B (84%) than those mediated by the GluN1a
      GluN2A (50%) subunits. At 500 uM, EAR18 blocked to a similar extent the NMDA
      evoked currents mediated by the GluN1a-GluN2B (62%) and the GluN1a-GluN2A (55%)
      subunits. CONCLUSIONS: The newly designed EAR16 and EAR18 peptides were shown to
      block in reversible manner NMDA-evoked currents, and EAR16 showed a stronger
      selectivity for GluN2B than for GluN2A.

PMID- 28511695
TI  - Absolute and relative accelerometer thresholds for determining the association
      between physical activity and metabolic syndrome in the older adults: The
      Generation-100 study.
AB  - BACKGROUND: When assessing population adherence to physical activity (PA)
      recommendation using accelerometers, absolute intensity threshold definition is
      applied despite having limited validity in those with low cardiorespiratory
      fitness (CRF), who are unable to reach them (e.g older adults). Thus, PA
      thresholds relative to CRF may be an alternative approach. We compared the
      proportion of the older adults meeting the PA recommendation when PA is assessed
      using absolute versus sex-and-CRF-adjusted (relative) accelerometer thresholds
      and determined the association between relative versus absolute moderate PA
      (MPA), vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) and metabolic
      syndrome (MetS). METHODS: Cross-sectional study of 509 men and 567 women aged 70
      77. Accelerometer assessed MPA, VPA and MVPA were analyzed using absolute and
      relative thresholds. Meeting the PA-recommendation was defined as amounting >=150
      min/week in MPA/MVPA or 75 min/week in VPA, respectively. CRF was directly
      measured as peak oxygen uptake (VO2peak). MetS was defined as 3 or more of the
      following: elevated waist circumference, fasting glucose, hypertension,
      triglycerides, decreased HDL-cholesterol or diabetes, dyslipidemia or
      hypertension medication. RESULTS: Higher proportion of the population met the
      recommendation when PA was assessed with relative compared to absolute
      thresholds: VPA (72.4% vs. 1.7%) and MVPA (75.2% vs. 33.8%). Logistic regression
      analysis revealed that men and women not meeting the relative-MVPA or VPA
      recommendation had higher likelihood of MetS (Men: MVPA OR: 1.59, 95% CI: 1.08
      2.33. VPA OR: 1.81, 95%CI: 1.23-2.67 and Women: MVPA OR: 2.12, 95% CI: 1.36-3.31;
      VPA OR: 1.95, 95% CI: 1.29-2.95), compared to men and women meeting the relative
      MVPA or VPA recommendation. There was no significant association between MetS and
      absolute MVPA, MPA or VPA recommendations in the fully adjusted model.
      CONCLUSIONS: The association between meeting/not meeting the PA recommendation
      and MetS differed with method. Not meeting relative MVPA and VPA recommendation
      was associated with significantly higher likelihood for presence of MetS. Since
      relative intensity is part of the current PA recommendation, it should be
      considered when assessing population PA and associated health risks in the older
      adults. TRIAL REGISTRATION: Clinical Trial Registration: NCT01931111 (Date of
      trial registration: July 19, 2013).

PMID- 28511694
TI  - Ethephon induced oxidative stress in the olive leaf abscission zone enables
      development of a selective abscission compound.
AB  - BACKGROUND: Table olives (Olea europaea L.), despite their widespread production,
      are still harvested manually. The low efficiency of manual harvesting and the
      rising costs of labor have reduced the profitability of this crop. A selective
      abscission treatment, inducing abscission of fruits but not leaves, is crucial
      for the adoption of mechanical harvesting of table olives. In the present work we
      studied the anatomical and molecular differences between the three abscission
      zones (AZs) of olive fruits and leaves. RESULTS: The fruit abscission zone 3
      (FAZ3), located between the fruit and the pedicel, was found to be the active AZ
      in mature fruits and is sensitive to ethephon, whereas FAZ2, between the pedicel
      and the rachis, is the flower active AZ as well as functioning as the most
      ethephon induced fruit AZ. We found anatomical differences between the leaf AZ
      (LAZ) and the two FAZs. Unlike the FAZs, the LAZ is characterized by small cells
      with less pectin compared to neighboring cells. In an attempt to differentiate
      between the fruit and leaf AZs, we examined the effect of treating olive-bearing
      trees with ethephon, an ethylene-releasing compound, with or without
      antioxidants, on the detachment force (DF) of fruits and leaves 5 days after the
      treatment. Ethephon treatment enhanced pectinase activity and reduced DF in all
      the three olive AZs. A transcriptomic analysis of the three olive AZs after
      ethephon treatment revealed induction of several genes encoding for hormones
      (ethylene, auxin and ABA), as well as for several cell wall degrading enzymes.
      However, up-regulation of cellulase genes was found only in the LAZ. Many genes
      involved in oxidative stress were induced by the ethephon treatment in the LAZ
      alone. In addition, we found that reactive oxygen species (ROS) mediated
      abscission in response to ethephon only in leaves. Thus, adding antioxidants such
      as ascorbic acid or butyric acid to the ethephon inhibited leaf abscission but
      enhanced fruit abscission. CONCLUSION: Our findings suggest that treating olive
      bearing trees with a combination of ethephon and antioxidants reduces the
      detachment force (DF) of fruit without weakening that of the leaves. Hence, this
      selective abscission treatment may be used in turn to promote mechanized harvest
      of olives.

PMID- 28511696
TI  - Variant effect prediction tools assessed using independent, functional assay
      based datasets: implications for discovery and diagnostics.
AB  - BACKGROUND: Genetic variant effect prediction algorithms are used extensively in
      clinical genomics and research to determine the likely consequences of amino acid
      substitutions on protein function. It is vital that we better understand their
      accuracies and limitations because published performance metrics are confounded
      by serious problems of circularity and error propagation. Here, we derive three
      independent, functionally determined human mutation datasets, UniFun, BRCA1-DMS
      and TP53-TA, and employ them, alongside previously described datasets, to assess
      the pre-eminent variant effect prediction tools. RESULTS: Apparent accuracies of
      variant effect prediction tools were influenced significantly by the benchmarking
      dataset. Benchmarking with the assay-determined datasets UniFun and BRCA1-DMS
      yielded areas under the receiver operating characteristic curves in the modest
      ranges of 0.52 to 0.63 and 0.54 to 0.75, respectively, considerably lower than
      observed for other, potentially more conflicted datasets. CONCLUSIONS: These
      results raise concerns about how such algorithms should be employed, particularly
      in a clinical setting. Contemporary variant effect prediction tools are unlikely
      to be as accurate at the general prediction of functional impacts on proteins as
      reported prior. Use of functional assay-based datasets that avoid prior
      dependencies promises to be valuable for the ongoing development and accurate
      benchmarking of such tools.

PMID- 28511697
TI  - Immunohistology and remodeling in fatal pediatric and adolescent asthma.
AB  - BACKGROUND: Thickening of reticular basement membrane, increased airway smooth
      muscle mass and eosinophilic inflammation are found in adult fatal asthma. At the
      present study the histopathology of fatal paediatric and adolescent asthma is
      evaluated. METHODS: Post-mortem lung autopsies from 12 fatal asthma cases and 8
      non-asthmatic control subjects were examined. Thickness of reticular basement
      membrane (RBM) and percentage of airway smooth muscle (ASM%) mass area were
      measured and inflammatory cells were counted. Patient records were reviewed for
      clinical history. RESULTS: The age range of the cases was from 0.9 to 19.5 years,
      eight were males and five had received inhaled corticosteroids. Thickened RBM was
      detected in majority of the cases without any correlation to treatment delay, age
      at onset of symptoms or diagnosis. In the large airways ASM was clearly increased
      in one third of the cases whereas the median ASM% did not differ from that in
      healthy controls (14.0% vs. 14.0%). In small airways no increase of ASM was
      found, instead mucous plugs were seen in fatal asthma. The number of eosinophils,
      plasmacytoid dendritic cells, macrophages, and B-cells were significantly
      increased in fatal asthma cases compared with controls and the two latter
      correlated with the length of the fatal exacerbation. CONCLUSIONS: The findings
      highlight the strong presence of eosinophils and mucous plugs even in small
      airways in children and adolescents with fatal asthma. Thickened RBM was obvious
      in majority of the patients. Contrary to our hypothesis, increased ASM% was
      detected in only one third of the patients.

PMID- 28511698
TI  - Using a mobile health application to reduce alcohol consumption: a mixed-methods
      evaluation of the drinkaware track & calculate units application.
AB  - BACKGROUND: Smartphone applications ("apps") offer promise as tools to help
      people monitor and reduce their alcohol consumption. To date, few evaluations of
      alcohol reduction apps exist, with even fewer considering apps already available
      to the public. The aim of this study was to evaluate an existing publically
      available app, designed by Drinkaware, a UK-based alcohol awareness charity.
      METHODS: We adopted a mixed-methods design, analysing routinely collected app
      usage data to explore user characteristics and patterns of usage. Following this,
      in-depth interviews were conducted with a sub-sample of app users to examine
      perceptions of acceptability, usability and perceived effectiveness, as well as
      to provide recommendations on how to improve the app. RESULTS: One hundred
      nineteen thousand seven hundred thirteen people downloaded and entered data into
      the app over a 13-month period. High attrition was observed after 1 week. Users
      who engaged with the app tended to be "high risk" drinkers and to report being
      motivated "to reduce drinking" at the point of first download. In those who
      consistently engaged with the app over time, self-reported alcohol consumption
      levels reduced, with most change occurring in the first week of usage. Our
      qualitative findings indicate satisfaction with the usability of the app, but
      mixed feedback was given regarding individual features. Users expressed
      conflicting views concerning the type of feedback and notifications that the app
      currently provides. A common preference was expressed for more personalised
      content. CONCLUSIONS: The Drinkaware app is a useful tool to support behaviour
      change in individuals who are already motivated and committed to reducing their
      alcohol consumption. The Drinkaware app would benefit from greater
      personalisation and tailoring to promote longer term use. This evaluation
      provides insight into the usability and acceptability of various app features and
      contains a number of recommendations for improving user satisfaction and the
      potential effectiveness of apps designed to encourage reductions in alcohol
      consumption.

PMID- 28511699
TI  - Does intraoperative closed-suction drainage influence the rate of pancreatic
      fistula after pancreaticoduodenectomy?
AB  - BACKGROUND: Although drainage of pancreatic anastomoses after
      pancreaticoduodenectomy (PD) is still debated, it remains recommended, especially
      in patients with a high risk of post-operative pancreatic fistula (POPF).
      Modalities of drainage of pancreatic anastomoses, especially the use of passive
      (PAD) or closed-suction (CSD) drains, and their impact on surgical outcomes, have
      been poorly studied. The aim was to compare CSD versus PAD on surgical outcomes
      after PD. METHODS: Retrospective analysis of 197 consecutive patients who
      underwent a standardized PD at two tertiary centers between March 2012 and April
      2015. Patients with PAD (n = 132) or CSD (n = 65) were compared. RESULTS: There
      was no significant difference in terms of 30-day overall and severe post
      operative morbidity, post-operative hemorrhage, post-operative intra-abdominal
      fluid collections, 90-day post-operative mortality and mean length of hospital
      stay. The rate of POPF was significantly increased in the CSD group (47.7% vs.
      32.6%; p = 0.04). CSD was associated with an increase of grade A POPF (21.5% vs.
      8.3%; p = 0.03), while clinically relevant POPF were not impacted. In patients
      with grade A POPF, the rate of undrained intra-abdominal fluid collections was
      increased in the PAD group (46.1% vs. 21.4%; p = 0.18). After multivariate
      analysis, CSD was an independent factor associated with an increased rate of POPF
      (OR = 2.43; p = 0.012). CONCLUSIONS: There was no strongly relevant difference in
      terms of surgical outcomes between PAD or CSD of pancreatic anastomoses after PD,
      but CSD may help to decrease the rate of undrained post-operative intra-abdominal
      collections in some patients. Further randomized, multi-institutional studies are
      needed.

PMID- 28511700
TI  - A new, easy-to-make pectin-honey hydrogel enhances wound healing in rats.
AB  - BACKGROUND: Honey, alone or in combination, has been used for wound healing since
      ancient times and has reemerged as a topic of interest in the last decade. Pectin
      has recently been investigated for its use in various biomedical applications
      such as drug delivery, skin protection, and scaffolding for cells. The aim of the
      present study was to develop and evaluate a pectin-honey hydrogel (PHH) as a
      wound healing membrane and to compare this dressing to liquid honey. METHODS:
      Thirty-six adult male Sprague-Dawley rats were anesthetized and a 2 * 2 cm
      excisional wound was created on the dorsum. Animals were randomly assigned to
      four groups (PHH, LH, Pec, and C): in the PHH group, the pectin-honey hydrogel
      was applied under a bandage on the wound; in the LH group, liquid Manuka honey
      was applied; in the Pec group, pectin hydrogel was applied (Pec); and in the C
      group, only bandage was applied to the wound. Images of the wound were taken at
      defined time points, and the wound area reduction rate was calculated and
      compared between groups. RESULTS: The wound area reduction rate was faster in the
      PHH, LH, and Pec groups compared to the control group and was significantly
      faster in the PHH group. Surprisingly, the Pec group exhibited faster wound
      healing than the LH group, but this effect was not statistically significant.
      CONCLUSION: This is the first study using pectin in combination with honey to
      produce biomedical hydrogels for wound treatment. The results indicate that the
      use of PHH is effective for promoting and accelerating wound healing.

PMID- 28511702
TI  - What is the evidence for the management of patients along the pathway from the
      emergency department to acute admission to reduce unplanned attendance and
      admission? An evidence synthesis.
AB  - BACKGROUND: Globally, the rate of emergency hospital admissions is increasing.
      However, little evidence exists to inform the development of interventions to
      reduce unplanned Emergency Department (ED) attendances and hospital admissions.
      The objective of this evidence synthesis was to review the evidence for
      interventions, conducted during the patient's journey through the ED or acute
      care setting, to manage people with an exacerbation of a medical condition to
      reduce unplanned emergency hospital attendance and admissions. METHODS: A rapid
      evidence synthesis, using a systematic literature search, was undertaken in the
      electronic data bases of MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of
      Science, for the years 2000-2014. Evidence included in this review was restricted
      to Randomised Controlled Trials (RCTs) and observational studies (with a control
      arm) reported in peer-reviewed journals. Studies evaluating interventions for
      patients with an acute exacerbation of a medical condition in the ED or acute
      care setting which reported at least one outcome related to ED attendance or
      unplanned admission were included. RESULTS: Thirty papers met our inclusion
      criteria: 19 intervention studies (14 RCTs) and 11 controlled observational
      studies. Sixteen studies were set in the ED and 14 were conducted in an acute
      setting. Two studies (one RCT), set in the ED were effective in reducing ED
      attendance and hospital admission. Both of these interventions were initiated in
      the ED and included a post-discharge community component. Paradoxically 3 ED
      initiated interventions showed an increase in ED re-attendance. Six studies (1
      RCT) set in acute care settings were effective in reducing: hospital admission,
      ED re-attendance or re-admission (two in an observation ward, one in an ED
      assessment unit and three in which the intervention was conducted within 72 h of
      admission). CONCLUSIONS: There is no clear evidence that specific interventions
      along the patient journey from ED arrival to 72 h after admission benefit ED re
      attendance or readmission. Interventions targeted at high-risk patients,
      particularly the elderly, may reduce ED utilization and warrant future research.
      Some interventions showing effectiveness in reducing unplanned ED attendances and
      admissions are delivered by appropriately trained personnel in an environment
      that allows sufficient time to assess and manage patients.

PMID- 28511701
TI  - Easi-CRISPR: a robust method for one-step generation of mice carrying conditional
      and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins.
AB  - BACKGROUND: Conditional knockout mice and transgenic mice expressing
      recombinases, reporters, and inducible transcriptional activators are key for
      many genetic studies and comprise over 90% of mouse models created. Conditional
      knockout mice are generated using labor-intensive methods of homologous
      recombination in embryonic stem cells and are available for only ~25% of all
      mouse genes. Transgenic mice generated by random genomic insertion approaches
      pose problems of unreliable expression, and thus there is a need for targeted
      insertion models. Although CRISPR-based strategies were reported to create
      conditional and targeted-insertion alleles via one-step delivery of targeting
      components directly to zygotes, these strategies are quite inefficient. RESULTS:
      Here we describe Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR), a
      targeting strategy in which long single-stranded DNA donors are injected with pre
      assembled crRNA + tracrRNA + Cas9 ribonucleoprotein (ctRNP) complexes into mouse
      zygotes. We show for over a dozen loci that Easi-CRISPR generates correctly
      targeted conditional and insertion alleles in 8.5-100% of the resulting live
      offspring. CONCLUSIONS: Easi-CRISPR solves the major problem of animal genome
      engineering, namely the inefficiency of targeted DNA cassette insertion. The
      approach is robust, succeeding for all tested loci. It is versatile, generating
      both conditional and targeted insertion alleles. Finally, it is highly efficient,
      as treating an average of only 50 zygotes is sufficient to produce a correctly
      targeted allele in up to 100% of live offspring. Thus, Easi-CRISPR offers a
      comprehensive means of building large-scale Cre-LoxP animal resources.

PMID- 28511703
TI  - Mindfulness-based stress reduction for people with multiple sclerosis - a
      feasibility randomised controlled trial.
AB  - BACKGROUND: Multiple sclerosis (MS) is a stressful condition. Mental health
      comorbidity is common. Stress can increase the risk of depression, reduce quality
      of life (QOL), and possibly exacerbate disease activity in MS. Mindfulness-Based
      Stress Reduction (MBSR) may help, but has been little studied in MS, particularly
      among more disabled individuals. METHODS: The objective of this study was to test
      the feasibility and likely effectiveness of a standard MBSR course for people
      with MS. Participant eligibility included: age > 18, any type of MS, an Expanded
      Disability Status Scale (EDSS) </= 7.0. Participants received either MBSR or wait
      list control. Outcome measures were collected at baseline, post-intervention, and
      three-months later. Primary outcomes were perceived stress and QOL. Secondary
      outcomes were common MS symptoms, mindfulness, and self-compassion. RESULTS:
      Fifty participants were recruited and randomised (25 per group). Trial retention
      and outcome measure completion rates were 90% at post-intervention, and 88% at 3
      months. Sixty percent of participants completed the course. Immediately post
      MBSR, perceived stress improved with a large effect size (ES 0.93; p < 0.01),
      compared to very small beneficial effects on QOL (ES 0.17; p = 0.48). Depression
      (ES 1.35; p < 0.05), positive affect (ES 0.87; p = 0.13), anxiety (ES 0.85; p =
      0.05), and self-compassion (ES 0.80; p < 0.01) also improved with large effect
      sizes. At three-months post-MBSR (study endpoint) improvements in perceived
      stress were diminished to a small effect size (ES 0.26; p = 0.39), were
      negligible for QOL (ES 0.08; p = 0.71), but were large for mindfulness (ES 1.13;
      p < 0.001), positive affect (ES 0.90; p = 0.54), self-compassion (ES 0.83; p <
      0.05), anxiety (ES 0.82; p = 0.15), and prospective memory (ES 0.81; p < 0.05).
      CONCLUSIONS: Recruitment, retention, and data collection demonstrate that a RCT
      of MBSR is feasible for people with MS. Trends towards improved outcomes suggest
      that a larger definitive RCT may be warranted. However, optimisation changes may
      be required to render more stable the beneficial treatment effects on stress and
      depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02136485 ; trial
      registered 1st May 2014.

PMID- 28511704
TI  - The use of kDNA minicircle subclass relative abundance to differentiate between
      Leishmania (L.) infantum and Leishmania (L.) amazonensis.
AB  - BACKGROUND: Leishmaniasis is a neglected disease caused by many Leishmania
      species, belonging to subgenera Leishmania (Leishmania) and Leishmania (Viannia).
      Several qPCR-based molecular diagnostic approaches have been reported for
      detection and quantification of Leishmania species. Many of these approaches use
      the kinetoplast DNA (kDNA) minicircles as the target sequence. These assays had
      potential cross-species amplification, due to sequence similarity between
      Leishmania species. Previous works demonstrated discrimination between L.
      (Leishmania) and L. (Viannia) by SYBR green-based qPCR assays designed on kDNA,
      followed by melting or high-resolution melt (HRM) analysis. Importantly, these
      approaches cannot fully distinguish L. (L.) infantum from L. (L.) amazonensis,
      which can coexist in the same geographical area. METHODS: DNA from 18
      strains/isolates of L. (L.) infantum, L. (L.) amazonensis, L. (V.) braziliensis,
      L. (V.) panamensis, L. (V.) guyanensis, and 62 clinical samples from L. (L.)
      infantum-infected dogs were amplified by a previously developed qPCR (qPCR-ML)
      and subjected to HRM analysis; selected PCR products were sequenced using an ABI
      PRISM 310 Genetic Analyzer. Based on the obtained sequences, a new SYBR-green
      qPCR assay (qPCR-ama) intended to amplify a minicircle subclass more abundant in
      L. (L.) amazonensis was designed. RESULTS: The qPCR-ML followed by HRM analysis
      did not allow discrimination between L. (L.) amazonensis and L. (L.) infantum in
      53.4% of cases. Hence, the novel SYBR green-based qPCR (qPCR-ama) has been
      tested. This assay achieved a detection limit of 0.1 pg of parasite DNA in
      samples spiked with host DNA and did not show cross amplification with
      Trypanosoma cruzi or host DNA. Although the qPCR-ama also amplified L. (L.)
      infantum strains, the Cq values were dramatically increased compared to qPCR-ML.
      Therefore, the combined analysis of Cq values from qPCR-ML and qPCR-ama allowed
      to distinguish L. (L.) infantum and L. (L.) amazonensis in 100% of tested
      samples. CONCLUSIONS: A new and affordable SYBR-green qPCR-based approach to
      distinguish between L. (L.) infantum and L. (L.) amazonensis was developed
      exploiting the major abundance of a minicircle sequence rather than targeting a
      hypothetical species-specific sequence. The fast and accurate discrimination
      between these species can be useful to provide adequate prognosis and treatment.

PMID- 28511705
TI  - PD-L1 expressing circulating tumour cells in head and neck cancers.
AB  - BACKGROUND: Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a
      promising immunotherapeutic approach for the management and treatment of head and
      neck cancer patients who do not respond to 1st/2nd line therapy. However, as
      checkpoint inhibitors are cost intensive, identifying patients who would most
      likely benefit from anti PD-L1 therapy is required. Developing a non-invasive
      technique would be of major benefit to the patient and to the health care system.
      CASE PRESENTATION: We report the case of a 56 year old man affected by a
      supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right
      jugulodigastric node and suspicious lung lesions. The lung lesion was biopsied
      and confirmed to be consistent with SCC. The patient was offered palliative
      chemotherapy. At the time of presentation, a blood sample was taken for
      circulating tumour cell (CTC) analysis. The dissemination of cancer was confirmed
      by the detection of CTCs in the peripheral blood of the patient, measured by the
      CellSearch System (Janssen Diagnostics). Using marker-independent, low-shear
      spiral microfluidic technology combined with immunocytochemistry, CTC clusters
      were found in this patient at the same time point, expressing PD-L1. CONCLUSION:
      This report highlights the potential use of CTCs to identify patients which might
      respond to anti PD-L1 therapy.

PMID- 28511707
TI  - Rapid deployment valve system shortens operative times for aortic valve
      replacement through right anterior minithoracotomy.
AB  - BACKGROUND: There is growing evidence from the literature that right anterior
      minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome.
      However, increased cross clamp time is the strongest argument for surgeons not
      performing RAT-AVR. Rapid deployment aortic valve systems have the potential to
      decrease cross-clamp time and ease this procedure. We assessed clinical outcome
      of rapid deployment and conventional valves through RAT. METHODS: Sixty-eight
      patients (mean age 76 +/- 6 years, 32% females) underwent RAT-AVR between 9/2013
      and 7/2015. According to the valve type implanted the patients were divided into
      two groups. In 43 patients (R-group; mean age 74.1 +/- 6.6 years) a rapid
      deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine,
      Calif) and in 25 patients (C-group; mean age 74.2 +/- 6.6 years) a conventional
      stented biological aortic valve was implanted. RESULTS: Aortic cross-clamp (42.1
      +/- 12 min vs. 68.3 +/- 20.3 min; p < 0.001) and bypass time (80.4 +/- 39.3 min
      vs. 106.6 +/- 23.2 min; p = 0.001) were shorter in the rapid deployment group (R
      group). We observed no differences in clinical outcome. Postoperative gradients
      (R-group: max gradient, 14.3 +/- 8 mmHg vs. 15.5 +/- 5 mmHg (C-group), mean
      gradient, 9.2 +/- 1.7 mmHg (R-group) vs. 9.1 +/- 2.3 mmHg (C-group) revealed no
      differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23
      27 mm vs. 23 mm; IQR 21-25; p = 0.009). CONCLUSIONS: Our data suggest that the
      rapid deployment aortic valve system reduced cross clamp and bypass time in
      patients undergoing RAT-AVR with similar hemodynamics as with larger size stented
      prosthesis. However, larger studies and long-term follow-up are mandatory to
      confirm our findings.

PMID- 28511708
TI  - Enzyme-mediated formulation of stable elliptical silver nanoparticles tested
      against clinical pathogens and MDR bacteria and development of antimicrobial
      surgical thread.
AB  - BACKGROUND: Silver nanoparticles (AgNPs) are believed to be emerging tool against
      various infectious diseases including multi-drug resistant (MDR) bacteria. In the
      present study, in vitro synthesis of AgNPs was optimized using 1:50 ratio of
      macerozyme (25 MUg/MUl) and 1 mM AgNO3 incubated at 80  degrees C for 8 h. AgNPs
      were characterized by UV-Visible spectroscopy, dynamic light scattering (DLS),
      scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission
      electron microscopy (TEM) and X-ray diffraction (XRD). RESULTS: Characterization
      studies suggest the synthesis of elliptical, stable and crystalline AgNPs with an
      average size of 38.26 +/- 0.4 nm calculated using TEM. The XRD pattern revealed
      the face-centered-cubic (fcc) form of metallic silver. Good shape integrity and
      dispersion of AgNPs after 1 year of incubation confirmed their stability. AgNPs
      were exibited the antimicrobial property against ten pathogenic bacteria, three
      molds and one yeast. The AgNPs also revealed remarkable antimicrobial activity
      against three MDR strains i.e. Extended spectrum beta-lactamase positive
      Escherichia coli, Staphylococcus aureus (MRSA) and Teicoplanin resistant
      Streptococcus Pneumoniae. The AgNPs coated surgical threads (suture) were
      revealed the remarkble antibacterial activity against three MDR strains. This is
      the first report to synthesize antimicrobial elliptical AgNPs using enzymes.
      CONCLUSION: The results suggest the possibilities to develop the nanoparticles
      coated antimicrobial medical fabric to combat against MDR infection.

PMID- 28511709
TI  - Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem
      high-dose chemotherapy and autologous stem cell transplantation for high-risk
      neuroblastoma: results of the SMC NB-2009 study.
AB  - BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk
      neuroblastomas, which incorporated total-body irradiation (TBI) with second high
      dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the
      survival rate was encouraging; however, short- and long-term toxicities were
      significant. In the present SMC NB-2009 study, only TBI was replaced with 131I
      meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS:
      From January 2009 to December 2013, 54 consecutive patients were assigned to
      receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC
      (carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa +
      melphalan) regimen with (for metastatic MIBG avid tumors) or without (for
      localized or MIBG non-avid tumors) 131I-MIBG treatment (18 or 12 mCi/kg) were
      used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with
      13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered
      after tandem HDCT/auto-SCT. RESULTS: Fifty-two patients underwent the first
      HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no
      significant immediate toxicity during the 131I-MIBG infusion. Acute toxicities
      during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the
      NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and
      glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less
      significant in the NB-2009 study than in NB-2004 study. There was no difference
      in the 5-year event-free survival (EFS) between the two studies (67.5 +/- 6.7%
      versus 58.3 +/- 6.9%, P = 0.340). CONCLUSIONS: Incorporation of high-dose 131I
      MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term
      toxicities associated with TBI, without jeopardizing the survival rate. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT03061656.

PMID- 28511710
TI  - Association between leisure time physical activity preference and behavior:
      evidence from the China Health & Nutrition Survey, 2004-2011.
AB  - BACKGROUND: Previous studies have suggested that food preference is a good
      indicator of actual food intake and that sedentary activity preference is a
      significant predictor of lower physical activity level. But no studies have
      examined the direct relationship between leisure time physical activity (LTPA)
      preferences and actual LTPA behavior, especially studies using longitudinal data.
      This study seeks to determine the association between these two variables, and to
      assess whether the association differs between urban and rural areas in China.
      METHODS: A total of 2427 Chinese adults were included in the analysis. Spearman
      correlation coefficients were used to test the association between leisure time
      physical activity preference and behavior, followed by multiple logistic
      regressions to further examine the association after adjusting for possible
      confounding variables. Urban-rural differences in the association were
      investigated through stratified analysis. RESULTS: In the sample, 63.0% were from
      urban areas, 47.4% were men, and the mean age was 40. Adjusted estimates based on
      logistic regression show that LTPA preference was a significant predictor of
      actual LTPA behavior (OR = 1.05, 95% CI = 1.01-1.09). The correlation was found
      to be significant among urban residents (OR = 1.06, 95% CI = 1.01-1.10), but not
      in rural residents. CONCLUSIONS: The study illustrates the predictive value of
      LTPA preference for actual LTPA behavior. Changing LTPA preference to promote
      LTPA may be helpful in preventing and controlling chronic disease in China.

PMID- 28511706
TI  - Analgesic antipyretic use among young children in the TEDDY study: no association
      with islet autoimmunity.
AB  - BACKGROUND: The use of analgesic antipyretics (ANAP) in children have long been a
      matter of controversy. Data on their practical use on an individual level has,
      however, been scarce. There are indications of possible effects on glucose
      homeostasis and immune function related to the use of ANAP. The aim of this study
      was to analyze patterns of analgesic antipyretic use across the clinical centers
      of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective
      cohort study and test if ANAP use was a risk factor for islet autoimmunity.
      METHODS: Data were collected for 8542 children in the first 2.5 years of life.
      Incidence was analyzed using logistic regression with country and first child
      status as independent variables. Holm's procedure was used to adjust for
      multiplicity of intercountry comparisons. Time to autoantibody seroconversion was
      analyzed using a Cox proportional hazards model with cumulative analgesic use as
      primary time dependent covariate of interest. For each categorization, a
      generalized estimating equation (GEE) approach was used. RESULTS: Higher
      prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared
      to Finland (78.1%) and Germany (80.2%). First-born children were more commonly
      given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non
      Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p =
      0.002). Acetaminophen and NSAID use in the absence of fever and infection was
      more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland
      and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not
      predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99
      1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever
      weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95%
      CI 1.01-1.09; p = 0.024). CONCLUSIONS: ANAP use in young children is not a risk
      factor for seroconversion by age 6 years. Use of ANAP is widespread in young
      children, and significantly higher in the U.S. compared to other study sites,
      where use is common also in absence of fever and infection.

PMID- 28511712
TI  - What we learned from extended culture of 'rejected' day-3 cleavage stage embryos:
      a prospective cohort study.
AB  - BACKGROUND: To test whether poor quality day-3 embryos can undergo successful
      blastulation and implantation. METHODS: A prospective cohort study was conducted.
      Whether or not a good quality embryo was transferred on day-3, poor quality
      (rejected) embryos were further cultured and followed. The clinical outcome of
      each embryo was assessed. RESULTS: A total of 694 rejected embryos (from 205
      patients) were included, with a blastulation rate of 21.2% (147 embryos) compared
      to 64.2% general blastulation rate reported by our laboratory (P < 0.01). In a
      multivariate logistic regression model, only their grade on day-3 significantly
      affected blastulation (P = 0.01). A total of 97 embryos attained eligibility for
      fresh transfer or cryopreservation, only 6 of which resulted from a day-3 embryo
      scored < 2. Of these, 52 were transferred, resulting in 21 pregnancies (16
      clinical and 5 chemical). In summary, 694 cultured embryos yielded 16 clinical
      pregnancies; a 2.3% clinical pregnancy rate. CONCLUSIONS: Low score day-3 embryos
      can result in successful blastulation and clinical pregnancies. However, the
      normal blastulation rate is poor.

PMID- 28511711
TI  - SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney
      disease.
AB  - Diabetic kidney disease (DKD) is the most common cause of end stage renal
      disease. The comprehensive management of DKD depends on combined target-therapies
      for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium
      glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral
      hypoglycemic agents acted on renal proximal tubules, suppress glucose
      reabsorption and increase urinary glucose excretion. Besides improvements in
      glycemic control, they presented excellent performances in direct renoprotective
      effects and the cardiovascular (CV) safety by decreasing albuminuria and the
      independent CV risk factors such as body weight and blood pressure, etc.
      Simultaneous use of SGLT-2 inhibitors and renin-angiotensin-aldosterone system
      (RAAS) blockers are novel strategies to slow the progression of DKD via reducing
      inflammatory and fibrotic markers induced by hyperglycaemia more than either drug
      alone. The available population and animal based studies have described SGLT2
      inhibitors plus RAAS blockers. The present review was to systematically review
      the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl
      peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists,
      mineralocorticoid receptor antagonists, and especially the angiotensin-converting
      enzyme inhibitors/angiotensin receptor blockers.

PMID- 28511714
TI  - Assessing equity in the distribution of high-technology medical equipment in
      Guangxi: evidence from an ethnic minority region in Southern China.
AB  - BACKGROUND: High-technology medical equipment (HTME) are important health
      resources. However, there is unequal distribution of these equipment in favor of
      metropolis and well equipped health facilities. This study sought to examine the
      equity gaps in the distribution of HTME in Guangxi. The results of this study
      could shed light on the future HTME allocation in Guangxi Zhuang Autonomous
      Region. METHODS: Data related to HTME was sourced from a general investigation of
      all the hospitals of Guangxi. Concentration index was used to assess the equity
      status of HTME in Guangxi. RESULTS: Over all, the total amount of HTME in Guangxi
      had been increasing from 2011 to 2015, and the per million population HTME of
      five kinds were all increased at the same time. Meanwhile, the concentration
      indices ranged between 0.1020 and 0.4617. The five medical equipment were all
      concentrated among the rich. CONCLUSIONS: The possession of SPECT per million
      population in Guangxi is lower than the national average level while it is
      superior to the national average level for CT, MRI, DSA and LA. The equity status
      in the distribution of the five medical equipment has deteriorated since 2011. In
      2015, the equity status of CT was the best, while the equity status of MRI was
      the worst. Meanwhile, 45.1% of HTME were concentrated in Nanning, Guilin, and
      Liuzhou.

PMID- 28511713
TI  - Artemisinin-based combination therapy in pregnant women in Zambia: efficacy,
      safety and risk of recurrent malaria.
AB  - BACKGROUND: In Zambia, malaria is one of the leading causes of morbidity and
      mortality, especially among under five children and pregnant women. For the
      latter, the World Health Organization recommends the use of artemisinin-based
      combination therapy (ACT) in the second and third trimester of pregnancy. In a
      context of limited information on ACT, the safety and efficacy of three
      combinations, namely artemether-lumefantrine (AL), mefloquine-artesunate (MQAS)
      and dihydroartemisinin-piperaquine (DHAPQ) were assessed in pregnant women with
      malaria. METHODS: The trial was carried out between July 2010 and August 2013 in
      Nchelenge district, Luapula Province, an area of high transmission, as part of a
      multi-centre trial. Women in the second or third trimester of pregnancy and with
      malaria were recruited and randomized to one of the three study arms. Women were
      actively followed up for 63 days, and then at delivery and 1 year post-delivery.
      RESULTS: Nine hundred pregnant women were included, 300 per arm. PCR-adjusted
      treatment failure was 4.7% (12/258) (95% CI 2.7-8.0) for AL, 1.3% (3/235) (95% CI
      0.4-3.7) for MQAS and 0.8% (2/236) (95% CI 0.2-3.0) for DHAPQ, with significant
      risk difference between AL and DHAPQ (p = 0.01) and between AL and MQAS (p =
      0.03) treatments. Re-infections during follow up were more frequent in the AL
      (HR: 4.71; 95% CI 3.10-7.2; p < 0.01) and MQAS (HR: 1.59; 95% CI 1.02-2.46; p =
      0.04) arms compared to the DHAPQ arm. PCR-adjusted treatment failure was
      significantly associated with women under 20 years [Hazard Ratio (HR) 5.35 (95%
      CI 1.07-26.73; p = 0.04)] and higher malaria parasite density [3.23 (95% CI 1.03
      10.10; p = 0.04)], and still women under 20 years [1.78, (95% CI 1.26-2.52; p <
      0.01)] had a significantly higher risk of re-infection. The three treatments were
      generally well tolerated. Dizziness, nausea, vomiting, headache and asthenia as
      adverse events (AEs) were more common in MQAS than in AL or DHAPQ (p < 0.001).
      Birth outcomes were not significantly different between treatment arms.
      CONCLUSION: As new infections can be prevented by a long acting partner drug to
      the artemisinins, DHAPQ should be preferred in places as Nchelenge district where
      transmission is intense while in areas of low transmission intensity AL or MQAS
      may be used.

PMID- 28511716
TI  - Retraction Note to: Inotropic therapy for cardiac low output syndrome: comparison
      of hemodynamic effects of dopamine/dobutamine versus dopamine/dopexamine.

PMID- 28511717
TI  - Pancreatic beta-cell regeneration: advances in understanding the genes and
      signaling pathways involved.
AB  - Recent advances in beta-cell regeneration in vivo are providing insights into the
      mechanisms involved in the conversion of distinct pancreatic cell lineages into
      beta cells. These mechanisms mostly involve reactivation of the gene encoding the
      pancreatic endocrine cell-specifying transcription factor neurogenin-3.

PMID- 28511715
TI  - Erratum to: Elaboration of a nomogram to predict nonsentinel node status in
      breast cancer patients with positive sentinel node, intraoperatively assessed
      with one step nucleic amplification: Retrospective and validation phase.

PMID- 28511718
TI  - Simultaneous development of Kawasaki disease following acute human adenovirus
      infection in monozygotic twins: A case report.
AB  - BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. However, many
      studies have suggested that specific genetic factors and/or some infectious
      agents underlie the onset of KD. Previous studies have suggested that human
      adenovirus (HAdV) is one of the triggering pathogens of KD. Here, we report
      monozygotic twin boys who sequentially developed KD in conjunction with acute
      HAdV type 3 (HAdV-3) infection. CASE PRESENTATION: The patients were four-year
      old monozygotic twin boys. The elder brother developed a high fever and was
      diagnosed with HAdV infection with an immunochromatographic kit for HAdV (IC
      kit). He was transferred to our institute after persistent fever for 7 days. On
      admission, he already fulfilled all the diagnostic criteria for KD. His
      laboratory data were as follows: WBC, 9700/MUl; CRP, 2.42 mg/dl; IFN-gamma, 99.8
      pg/ml; and TNF-alpha, 10.9 pg/ml. He received intravenous immunoglobulin (IVIG)
      and aspirin and responded well, with no coronary artery abnormalities. The
      younger brother, who was also IC-kit-positive, was hospitalized on the same day
      as his elder brother after persistent fever for 3 days. His data on admission
      were as follows: WBC, 12,600/MUl; CRP, 5.54 mg/dl; IFN-gamma, 105.0 pg/ml; and
      TNF-alpha, 33.6 pg/ml. Although he developed all of the typical KD symptoms by
      day 4, his fever subsided spontaneously on day 6 without IVIG or aspirin.
      However, he developed a dilation of the coronary artery in the region of the left
      circumflex artery bifurcation on day 10. His coronary artery dilation had
      resolved 3 months after onset. HAdV-3 DNA was detected with PCR in stool samples
      from both patients, and HAdV3 was isolated from the younger brother's stool
      sample. Serum neutralizing antibodies to AdV3 were also significantly elevated in
      both patients, suggesting seroconversion. CONCLUSIONS: There have been few
      reports of the simultaneous development of KD in monozygotic twins. Notably, both
      twins had an acute HAdV-3 infection immediately before they developed KD. These
      cases strongly suggest that KD was triggered by HAdV-3 infection, and they
      indicate that specific immune responses to some pathogens (such as HAdV-3),
      arising from genetic susceptibility, play a critical role in the pathogenesis of
      KD.

PMID- 28511720
TI  - Identifying models of delivery, care domains and quality indicators relevant to
      palliative day services: a scoping review protocol.
AB  - BACKGROUND: With an ageing population and increasing numbers of people with life
      limiting illness, there is a growing demand for palliative day services. There is
      a need to measure and demonstrate the quality of these services, but there is
      currently little agreement on which aspects of care should be used to do this.
      The aim of the scoping review will be to map the extent, range and nature of the
      evidence around models of delivery, care domains and existing quality indicators
      used to evaluate palliative day services. METHODS: Electronic databases (MEDLINE,
      EMBASE, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials) will be
      searched for evidence using consensus development methods; randomised or quasi
      randomised controlled trials; mixed methods; and prospective, longitudinal or
      retrospective case-control studies to develop or test quality indicators for
      evaluating palliative care within non-residential settings, including day
      hospices and community or primary care settings. At least two researchers will
      independently conduct all searches, study selection and data abstraction
      procedures. Meta-analyses and statistical methods of synthesis are not planned as
      part of the review. Results will be reported using numerical counts, including
      number of indicators in each care domain and by using qualitative approach to
      describe important indicator characteristics. A conceptual model will also be
      developed to summarise the impact of different aspects of quality in a palliative
      day service context. Methodological quality relating to indicator development
      will be assessed using the Appraisal of Indicators through Research and
      Evaluation (AIRE) tool. Overall strength of evidence will be assessed using the
      Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
      system. Final decisions on quality assessment will be made via consensus between
      review authors. DISCUSSION: Identifying, developing and implementing evidence
      based quality indicators is critical to the evaluation and continued improvement
      of palliative care. Review findings will be used to support clinicians and
      policymakers make decisions on which quality indicators are most appropriate for
      evaluating day services at the patient and service level, and to identify areas
      for further research.

PMID- 28511719
TI  - Interleukin-10-producing LAG3+ regulatory T cells are associated with disease
      activity and abatacept treatment in rheumatoid arthritis.
AB  - BACKGROUND: Regulatory T cells (Tregs) play a role in the suppression of
      inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was
      reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify
      the function of human IL-10-producing CD4+CD25-LAG3+ T cells (LAG3+ Tregs) and
      their association with rheumatoid arthritis (RA). METHODS: LAG3+ Tregs of human
      peripheral blood mononuclear cells (PBMCs) were cultured with B cells and
      follicular helper T cells to examine antibody suppression effects. The frequency
      of LAG3+ Tregs was evaluated in peripheral blood samples from 101 healthy donors
      and 85 patients with RA. In patients treated with abatacept, PBMC samples were
      analyzed before and after treatment. Naive CD4+ T cells were sorted and cultured
      in the presence of abatacept, followed by flow cytometric analysis and function
      assays. RESULTS: LAG3+ Tregs produced high amounts of IL-10 and interferon-gamma,
      and they suppressed B-cell antibody production more strongly than CD25+ Tregs.
      Cell-to-cell contact was required for the suppressive function of LAG3+ Tregs.
      The frequency of LAG3+ Tregs was lower in patients with RA, especially those with
      higher Clinical Disease Activity Index scores. LAG3+ Tregs significantly
      increased after 6 months of abatacept treatment, whereas CD25+ Tregs generally
      decreased. Abatacept treatment in vitro conferred LAG3 and EGR2 expression on
      naive CD4+ T cells, and abatacept-treated CD4+ T cells exhibited suppressive
      activity. CONCLUSIONS: IL-10-producing LAG3+ Tregs are associated with the
      immunopathology and therapeutic response in RA. LAG3+ Tregs may participate in a
      mechanism for the anti-inflammatory and immune-modulating effects of targeted
      therapy for costimulation.

PMID- 28511722
TI  - Use of Rapid Ascertainment Process for Institutional Deaths (RAPID) to identify
      pregnancy-related deaths in tertiary-care obstetric hospitals in three
      departments in Haiti.
AB  - BACKGROUND: Accurate assessment of maternal deaths is difficult in countries
      lacking standardized data sources for their review. As a first step to
      investigate suspected maternal deaths, WHO suggests surveillance of "pregnancy
      related deaths", defined as deaths of women while pregnant or within 42 days of
      termination of pregnancy, irrespective of cause. Rapid Ascertainment Process for
      Institutional Deaths (RAPID), a surveillance tool, retrospectively identifies
      pregnancy-related deaths occurring in health facilities that may be missed by
      routine surveillance to assess gaps in reporting these deaths. METHODS: We used
      RAPID to review pregnancy-related deaths in six tertiary obstetric care
      facilities in three departments in Haiti. We reviewed registers and medical
      dossiers of deaths among women of reproductive age occurring in 2014 and 2015
      from all wards, along with any additional available dossiers of deaths not
      appearing in registers, to capture pregnancy status, suspected cause of death,
      and timing of death in relation to the pregnancy. We used capture-recapture
      analyses to estimate the true number of in-hospital pregnancy-related deaths in
      these facilities. RESULTS: Among 373 deaths of women of reproductive age, we
      found 111 pregnancy-related deaths, 25.2% more than were reported through routine
      surveillance, and 22.5% of which were misclassified as non-pregnancy-related.
      Hemorrhage (27.0%) and hypertensive disorders (18.0%) were the most common
      categories of suspected causes of death, and deaths after termination of
      pregnancy were statistically significantly more common than deaths during
      pregnancy or delivery. Data were missing at multiple levels: 210 deaths had an
      undetermined pregnancy status, 48.7% of pregnancy-related deaths lacked specific
      information about timing of death in relation to the pregnancy, and capture
      recapture analyses in three hospitals suggested that approximately one-quarter of
      pregnancy-related deaths were not captured by RAPID or routine surveillance.
      CONCLUSIONS: Across six tertiary obstetric care facilities in Haiti, RAPID
      identified unreported pregnancy-related deaths, and showed that missing data was
      a widespread problem. RAPID is a useful tool to more completely identify facility
      based pregnancy-related deaths, but its repeated use would require a concomitant
      effort to systematically improve documentation of clinical findings in medical
      records. Limitations of RAPID demonstrate the need to use it alongside other
      tools to more accurately measure and address maternal mortality.

PMID- 28511723
TI  - Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node
      biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of
      diagnostic studies.
AB  - BACKGROUND: Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a
      promising diagnostic tool to assess accurately the status of lymph node
      metastasis in the surgical operation and assure the oncologic safety of the
      function or stomach preserving surgery. The diagnostic performance of this
      technology in recent studies varied. Thus, we conducted this meta-analysis.
      METHODS: This systematic review and meta-analysis was registered at the PROSPERO.
      Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and
      Cochrane Library databases. A random-effect model was used to pool the data.
      Summary receiver operator characteristic curves, analysis for publication bias,
      meta-regression, and subgroup analysis were also performed. RESULTS: The pooled
      SLN identification rate and sensitivity were 0.97 and 0.89. 99mTc-human serum
      albumin with indocyanine green (ICG), 99mTc-antimony sulfur colloid with ICG,
      performing SLN biopsy >=15 min after dye injection, an SLN >=5, the basin
      dissection, laparoscopic surgery, in studies conducted in Japan and studies
      published after 2012, were associated with higher sensitivity. CT1 stage,
      performing SLN biopsy >=15 min after dye injection, in studies conducted in Japan
      and studies published after 2012, were related with a higher identification rate.
      CONCLUSIONS: Dual tracer is promising in SLN biopsy in gastric cancer, and the
      clinical application of SLN biopsy should be limited to the patients of cT1N0M0
      gastric cancer. The combination of 99mTc-human serum albumin and ICG as well as
      the combination of 99mTc-antimony sulfur colloid and ICG may be the optimal
      tracer combination. However, it seems not justified to put this technique into
      routine clinical application recently. Some factors that might enhance diagnostic
      value are identified.

PMID- 28511724
TI  - Production of a recombinant swollenin from Trichoderma harzianum in Escherichia
      coli and its potential synergistic role in biomass degradation.
AB  - BACKGROUND: Fungal swollenins (SWOs) constitute a class of accessory proteins
      that are homologous to canonical plant expansins. Expansins and expansin-related
      proteins are well known for acting in the deagglomeration of cellulose structure
      by loosening macrofibrils. Consequently, SWOs can increase the accessibility and
      efficiency of the other enzymes involved in the saccharification of cellulosic
      substrates. Thus, SWOs are promising targets for improving the hydrolysis of
      plant biomass and for use as an additive to enhance the efficiency of an enzyme
      cocktail designed for the production of biofuels. RESULTS: Here, we report the
      initial characterization of an SWO from Trichoderma harzianum (ThSwo) that was
      successfully produced using Escherichia coli as a host. Initially, transcriptome
      and secretome data were used to compare swo gene expression and the amount of
      secreted ThSwo. The results from structural modeling and phylogenetic analysis of
      the ThSwo protein showed that ThSwo does preserve some structural features of the
      plant expansins and family-45 glycosyl hydrolase enzymes, but it evolutionarily
      diverges from both of these protein classes. Recombinant ThSwo was purified at a
      high yield and with high purity and showed secondary folding similar to that of a
      native fungal SWO. Bioactivity assays revealed that the purified recombinant
      ThSwo created a rough and amorphous surface on Avicel and displayed a high
      synergistic effect with a commercial xylanase from T. viride, enhancing its
      hydrolytic performance up to 147 +/- 7%. CONCLUSIONS: Many aspects of the
      structure and mechanism of action of fungal SWOs remain unknown. In the present
      study, we produced a recombinant, active SWO from T. harzianum using a
      prokaryotic host and confirmed its potential synergistic role in biomass
      degradation. Our work paves the way for further studies evaluating the structure
      and function of this protein, especially regarding its use in biotechnology.

PMID- 28511725
TI  - The performance of different classification criteria sets for spondyloarthritis
      in the worldwide ASAS-COMOSPA study.
AB  - BACKGROUND: In this study, we sought to compare the performance of
      spondyloarthritis (SpA) classification criteria sets in an international SpA
      cohort with patients included from five continents around the world. METHODS:
      Data from the (ASAS) COMOrbidities in SPondyloArthritis (ASAS-COMOSPA) study were
      used. ASAS-COMOSPA is a multinational, cross-sectional study with consecutive
      patients diagnosed with SpA by rheumatologists worldwide. Patients were
      classified according to the European Spondyloarthropathy Study Group (ESSG),
      modified European Spondyloarthropathy Study Group (mESSG), Amor, modified Amor,
      Assessment of SpondyloArthritis international Society (ASAS) axial
      Spondyloarthritis (axSpA), ASAS peripheral spondyloarthritis (pSpA) and
      ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria. Overlap
      between the classification criteria sets was assessed for patients with and
      without back pain. Furthermore, patients fulfilling different arms of the ASAS
      axSpA criteria (imaging arm, clinical arm, both arms) were compared on the
      presence of SpA features. RESULTS: A total of 3942 patients (5 continents, 26
      countries) were included. The mean age was 43.6 years, 65.0% were male, 56.2%
      were human leucocyte antigen B27-positive and 64.4% had radiographic sacroiliitis
      (based on modified New York criteria). Of the patients, 85.5% were classified by
      the ASAS SpA criteria (87.7% ASAS axSpA, 12.3% ASAS pSpA). Fulfilment of the
      Amor, ESSG and CASPAR criteria was present in 83.3%, 88.4% and 21.6% of patients,
      respectively. Of the patients with back pain (n = 3227), most were classified by
      all three of Amor, ESSG and ASAS axSpA criteria (71.4%). Patients fulfilling the
      imaging arm and the clinical arm of the ASAS axSpA criteria had similar
      presentations of SpA features. In patients without back pain, overlap between
      classification criteria sets was seen, although to a lesser extent. CONCLUSIONS:
      Most patients with a clinical diagnosis of axial SpA in the worldwide ASAS
      COMOSPA study fulfil several classification criteria sets, and a substantial
      overlap between different criteria sets is seen, which suggests a high level of
      credibility of the criteria. Large inter-regional differences in the fulfilment
      of classification criteria were not found. Patients fulfilling the clinical arm
      were remarkably similar to patients fulfilling the imaging arm with respect to
      the presence of most SpA features.

PMID- 28511721
TI  - Socioeconomic status and dietary patterns in children from around the world:
      different associations by levels of country human development?
AB  - BACKGROUND: Although 'unhealthy' diet is a well-known risk factor for non
      communicable diseases, its relationship with socio-economic status (SES) has not
      been fully investigated. Moreover, the available research has largely been
      conducted in countries at high levels of human development. This is the first
      study to examine relationships among dietary patterns and SES of children from
      countries spanning a wide range of human development. METHODS: This was a
      multinational cross-sectional study among 9-11 year-old children (n = 6808) from
      urban/peri-urban sites across 12 countries. Self-reported food frequency
      questionnaires were used to determine the children's dietary patterns. Principal
      Components Analysis was employed to create two component scores representing
      'unhealthy' and 'healthy' dietary patterns. Multilevel models accounting for
      clustering at the school and site level were used to examine the relationships
      among dietary patterns and SES. RESULTS: The mean age of participants in this
      study (53.7% girls) was 10.4 years. Largest proportions of total variance in
      dietary patterns occurred at the individual, site, and school levels (individual,
      school, site: 62.8%; 10.8%; 26.4% for unhealthy diet pattern (UDP) and 88.9%;
      3.7%; 7.4%) for healthy diet pattern (HDP) respectively. There were significant
      negative 'unhealthy' diet-SES gradients in 7 countries and positive 'healthy'
      diet-SES gradients in 5. Within country diet-SES gradients did not significantly
      differ by HDI. Compared to participants in the highest SES groups, unhealthy diet
      pattern scores were significantly higher among those in the lowest within-country
      SES groups in 8 countries: odds ratios for Australia (2.69; 95% CI: 1.33-5.42),
      Canada (4.09; 95% CI: 2.02-8.27), Finland (2.82; 95% CI: 1.27-6.22), USA (4.31;
      95% CI: 2.20-8.45), Portugal (2.09; 95% CI: 1.06-4.11), South Africa (2.77; 95%
      CI: 1.22-6.28), India (1.88; 95% CI: 1.12-3.15) and Kenya (3.35; 95% CI: 1.91
      5.87). CONCLUSIONS: This study provides evidence of diet-SES gradients across all
      levels of human development and that lower within-country SES is strongly related
      to unhealthy dietary patterns. Consistency in within-country diet-SES gradients
      suggest that interventions and public health strategies aimed at improving
      dietary patterns among children may be similarly employed globally. However,
      future studies should seek to replicate these findings in more representative
      samples extended to more rural representation.

PMID- 28511726
TI  - Executive Functioning in Pedophilia and Child Sexual Offending.
AB  - OBJECTIVES: Pedophilia (P) is a psychiatric disease associated with sexual
      attraction toward children and often accompanied by child sexual offending (CSO).
      Consequently, it is important to address the understanding of executive
      dysfunctions that may increase the probability of CSO. Moreover, this research
      field has been lacking to disentangle executive deficits associated with
      pedophilia (as a deviant sexual preference) from those associated with CSO (as a
      deviant sexual behavior). METHODS: The German multi-sided research network NeMUP
      offers the opportunity to overcome these limitations. By applying the Cambridge
      Automated Neuropsychological Test Battery in four carefully matched groups of
      men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual
      offending against children; (3) child molesters without pedophilia (N=19), and
      (4) non-offending controls (N=49), we were able to analyze executive functioning
      in pedophilia and CSO independently. RESULTS: Both CSO groups as compared to both
      non-CSO groups exhibited worsened response inhibition ability. However, only non
      pedophilic offenders showed additionally disabled strategy use ability. Regarding
      set-shifting abilities, the P+CSO group showed the best performance. We also
      found that performances were affected by age: only in pedophiles, response
      inhibition worsened with age, while age-related deficits in set-shifting
      abilities were restricted to non-pedophilic participants. The latter also
      differentiated between both sexual preference groups. CONCLUSIONS: Our results
      are the first to demonstrate that executive dysfunctions are related to offense
      status rather than pedophilic preference. Furthermore, there was evidence for
      differentiating age and performance correlations between pedophiles and non
      pedophiles, which warrants further investigation. (JINS, 2017, 23, 460-470).

PMID- 28511727
TI  - Rejection Sensitivity as a Moderator of Psychosocial Outcomes Following Pediatric
      Traumatic Brain Injury.
AB  - OBJECTIVES: The current study examines whether psychosocial outcomes following
      pediatric traumatic brain injury (TBI) vary as a function of children's rejection
      sensitivity (RS), defined as their disposition to be hypersensitive to cues of
      rejection from peers. METHODS: Children ages 8-13 with a history of severe TBI
      (STBI, n=16), complicated mild/moderate TBI (n=35), or orthopedic injury (OI,
      n=49) completed measures assessing self-esteem and RS on average 3.28 years post
      injury (SD=1.33, range=1.25-6.34). Parents reported on their child's emotional
      and behavioral functioning and social participation. RESULTS: Regression analyses
      found moderation of group differences by RS for three outcomes: social
      participation, self-perceptions of social acceptance, and externalizing behavior
      problems. Conditional effects at varying levels of RS indicated that
      externalizing problems and social participation were significantly worse for
      children with STBI at high levels of RS, compared to children with OI. Social
      participation for the STBI group remained significantly lower than the OI group
      at mean levels of RS, but not at low levels of RS. At high levels of RS, self
      perceptions of social acceptance were lower for children with moderate TBI
      compared to OI, but group differences were not significant at mean or low levels
      of RS. No evidence of moderation was found for global self-worth, self
      perceptions of physical appearance or athletic ability, or internalizing
      problems. CONCLUSIONS: The findings highlight the salient nature of social
      outcomes in the context of varying levels of RS. These findings may have
      implications for the design of interventions to improve social outcomes following
      TBI. (JINS, 2017, 23, 451-459).

PMID- 28511728
TI  - Birth weight interacts with a functional variant of the oxytocin receptor gene
      (OXTR) to predict executive functioning in children.
AB  - Genetic variation in the oxytocin receptor gene (OXTR) is associated with several
      psychiatric conditions characterized by deficits in executive functioning (EF). A
      specific OXTR variant, rs2254298, has previously been associated with brain
      functioning in regions implicated in EF. Moreover, birth weight variation across
      the entire range is associated with individual differences in cortical structure
      and function that underlie EF. This is the first study to examine the main and
      interactive effect between rs2254298 and birth weight on EF in children. The
      sample consisted of 310 children from an ongoing longitudinal study. EF was
      measured at age 4.5 using observational tasks indexing working memory, cognitive
      flexibility, and inhibitory control. A family-based design that controlled for
      population admixture, stratification, and nongenomic confounds was employed. A
      significant genetic association between rs2254298 and EF was observed, with more
      copies of the major allele (G) associated with higher EF. There was also a
      significant interaction between rs2254298 and birth weight, such that more copies
      of the major allele in combination with higher birth weight predicted better EF.
      Findings suggest that OXTR may be associated with discrete neurocognitive
      abilities in childhood, and these effects may be modulated by intrauterine
      conditions related to fetal growth and development.

PMID- 28511729
TI  - Juicy Conceptualizations: Increasing Alliance Through Attending to Client
      Metaphoric Language.
AB  - BACKGROUND: There is increasing interest in the use of metaphor in cognitive
      behaviour therapy. Experts advocate bringing client metaphors into case
      conceptualizations, but there is little empirical research to support this. AIMS:
      This study evaluated the effect of training 12 therapists to attend to client
      metaphors and bring them into case conceptualizations. METHOD: Pre- and post
      training role-played therapy sessions were conducted and video-recorded. Alliance
      was rated by role play 'clients' and an external expert rated the quality of the
      sessions and of the shared conceptualizations. RESULTS: There were significant
      increases in some ratings of alliance, based on role play 'client' ratings and
      external ratings of role plays of therapy sessions before and after training. The
      greater the difference between therapist and 'client' on a measure of preference
      for producing metaphor, the lower the rating of the session by the 'client' on
      the Bond factor score of an alliance measure, the Working Alliance Inventory.
      This result suggests that working metaphorically may be most effective when the
      therapist and client have a similar degree of preference for speaking
      metaphorically. CONCLUSION: This study provides preliminary support for the idea
      that attending to client metaphors during conceptualization can be beneficial for
      alliance.

PMID- 28511730
TI  - Simulation in Canadian postgraduate emergency medicine training - a national
      survey.
AB  - OBJECTIVES: Simulation-based education (SBE) is an important training strategy in
      emergency medicine (EM) postgraduate programs. This study sought to characterize
      the use of simulation in FRCPC-EM residency programs across Canada. METHODS: A
      national survey was administered to residents and knowledgeable program
      representatives (PRs) at all Canadian FRCPC-EM programs. Survey question themes
      included simulation program characteristics, the frequency of resident
      participation, the location and administration of SBE, institutional barriers,
      interprofessional involvement, content, assessment strategies, and attitudes
      about SBE. RESULTS: Resident and PR response rates were 63% (203/321) and 100%
      (16/16), respectively. Residents reported a median of 20 (range 0-150) hours of
      annual simulation training, with 52% of residents indicating that the time
      dedicated to simulation training met their needs. PRs reported the frequency of
      SBE sessions ranging from weekly to every 6 months, with 15 (94%) programs having
      an established simulation curriculum. Two (13%) of the programs used simulation
      for resident assessment, although 15 (94%) of PRs indicated that they would be
      comfortable with simulation-based assessment. The most common PR-identified
      barriers to administering simulation were a lack of protected faculty time (75%)
      and a lack of faculty experience with simulation (56%). Interprofessional
      involvement in simulation was strongly valued by both residents and PRs.
      CONCLUSIONS: SBE is frequently used by Canadian FRCPC-EM residency programs.
      However, there exists considerable variability in the structure, frequency, and
      timing of simulation-based activities. As programs transition to competency-based
      medical education, national organizations and collaborations should consider the
      variability in how SBE is administered.

PMID- 28511731
TI  - Dietary nitrate and blood pressure: evolution of a new nutrient?
AB  - Dietary nitrate is mainly obtained from vegetables, especially green leafy
      vegetables and beetroot. As a result of early research, dietary nitrate is
      currently viewed as a contaminant linked to increased risks of stomach cancer and
      methaemoglobinaemia. Consequently, nitrate levels are restricted in certain
      vegetables and in water supplies to ensure exposure levels remain below an
      acceptable daily intake of 3.7 mg/kg per d. The average nitrate intake in the UK
      is approximately 70 mg/d, although some population groups, such as vegetarians,
      may consume three times that amount. However, recent studies in the last decade
      suggest that dietary nitrate can significantly reduce systolic blood pressure via
      the nitrate-nitrite-NO pathway. A small, downward shift in systolic blood
      pressure across the population could significantly reduce the incidence of
      hypertension and mortality from CVD such as stroke. Interestingly, vegetarians
      tend to have lower levels of blood pressure than omnivores and epidemiological
      studies suggest that vegetarians have lower risks of CVD. Recent evidence is
      mainly focused on the acute effects of dietary nitrate supplementation and there
      is a lack of data looking at the chronic effects of high nitrate consumption in
      humans. Nevertheless, due to potential health benefits, some authors are
      recommending that nitrate should be considered as a nutrient necessary for
      health, rather than as a contaminant which needs to be restricted. This review
      will discuss the emerging role of dietary nitrate in the control of blood
      pressure and whether there is sufficient evidence to state that nitrate is a
      'new' nutrient.

PMID- 28511732
TI  - Outbreak of diarrhoea among participants of a triathlon and a duathlon on 12 July
      2015 in Utrecht, the Netherlands.
AB  - On 12 July 2015, a triathlon competition with 900 participants took place in
      Utrecht, the Netherlands. An outbreak investigation was initiated after 56
      participants reported health complaints. An online questionnaire was sent to 700
      participants. Stool specimens from six participants and four water specimens were
      collected from the swimming location. A total of 239 participants completed the
      questionnaire (response rate: 34%), 73 (31%) of them met the case definition for
      acute gastrointestinal illness (AGI). A total of 67% of the respondents were male
      and the median age was 38 years. Almost half (42%) of swimmers reported health
      complaints. Consumption of energy drinks and ingesting ?3 mouthfuls of canal
      water were identified as risk factors for AGI among swimmers only (adjusted
      relative risks (aRR) 1.6; 95% confidence intervals (CI) 1.0-2.5 and aRR 2.6; 95%
      CI 1.5-4.8). The collected water specimens tested positive for norovirus
      genogroup I and rotavirus and stool specimens tested positive for norovirus
      genogroup II. Our findings indicate that the outbreak could have been caused by
      exposure to norovirus during swimming. Swimmers should get information about the
      health risks for making an informed choice about participating. For future
      events, the organisers decided to change the swimming location from a canal to a
      recreational lake.

PMID- 28511733
TI  - Similarities and interactions between the ageing process and high chronic intake
      of added sugars.
AB  - In our societies, the proportions of elderly people and of obese individuals are
      increasing. Both factors are associated with high health-related costs. During
      obesity, many authors suggest that it is a high chronic intake of added sugars
      (HCIAS) that triggers the shift towards pathology. However, the majority of
      studies were performed in young subjects and only a few were interested in the
      interaction with the ageing process. Our purpose was to discuss the metabolic
      effects of HCIAS, compare with the effects of ageing, and evaluate how
      deleterious the combined action of HCIAS and ageing could be. This effect of
      HCIAS seems mediated by fructose, targeting the liver first, which may lead to
      all subsequent metabolic alterations. The first basic alterations induced by
      fructose are increased oxidative stress, protein glycation, inflammation,
      dyslipidaemia and insulin resistance. These alterations are also present during
      the ageing process, and are closely related to each other, one leading to the
      other. These basic alterations are also involved in more complex syndromes, which
      are also favoured by HCIAS, and present during ageing. These include non
      alcoholic fatty liver disease, hypertension, neurodegenerative diseases,
      sarcopenia and osteoporosis. Cumulative effects of ageing and HCIAS have been
      seldom tested and may not always be strictly additive. Data also suggest that
      some of the metabolic alterations that are more prevalent during ageing could be
      related more with nutritional habits than to intrinsic ageing. In conclusion, it
      is clear that HCIAS interacts with the ageing process, accelerates the
      accumulation of metabolic alterations, and that it should be avoided.

PMID- 28511734
TI  - Sleeping with one eye open: loneliness and sleep quality in young adults.
AB  - BACKGROUND: Feelings of loneliness are common among young adults, and are
      hypothesized to impair the quality of sleep. In the present study, we tested
      associations between loneliness and sleep quality in a nationally representative
      sample of young adults. Further, based on the hypothesis that sleep problems in
      lonely individuals are driven by increased vigilance for threat, we tested
      whether past exposure to violence exacerbated this association. METHOD: Data were
      drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth
      cohort of 2232 twins born in England and Wales in 1994 and 1995. We measured
      loneliness using items from the UCLA Loneliness Scale, and sleep quality using
      the Pittsburgh Sleep Quality Index. We controlled for covariates including social
      isolation, psychopathology, employment status and being a parent of an infant. We
      examined twin differences to control for unmeasured genetic and family
      environment factors. RESULTS: Feelings of loneliness were associated with worse
      overall sleep quality. Loneliness was associated specifically with subjective
      sleep quality and daytime dysfunction. These associations were robust to controls
      for covariates. Among monozygotic twins, within-twin pair differences in
      loneliness were significantly associated with within-pair differences in sleep
      quality, indicating an association independent of unmeasured familial influences.
      The association between loneliness and sleep quality was exacerbated among
      individuals exposed to violence victimization in adolescence or maltreatment in
      childhood. CONCLUSIONS: Loneliness is robustly associated with poorer sleep
      quality in young people, underscoring the importance of early interventions to
      mitigate the long-term outcomes of loneliness. Special care should be directed
      towards individuals who have experienced victimization.

PMID- 28511735
TI  - Addenbrooke's cognitive examination-revised: normative and accuracy data for
      seniors with heterogeneous educational level in Brazil.
AB  - BACKGROUND: Several cognitive tools have been developed aiming to diagnose
      dementia. The cognitive battery Addenbrooke's Cognitive Examination - Revised
      (ACE-R) has been used to detect cognitive impairment; however, there are few
      studies including samples with low education. The aim of the study was to provide
      ACE-R norms for seniors within a lower education, including illiterates. An
      additional aim was to examine the accuracy of the ACE-R to detect dementia and
      cognitive impairment no dementia (CIND). METHODS: Data originated from an
      epidemiological study conducted in the municipality of Tremembe, Brazil. The
      Brazilian version of ACE-R was applied as part of the cognitive assessment in all
      participants. Of the 630 participants, 385 were classified as cognitively normal
      (CN) and were included in the normative data set, 110 individuals were diagnosed
      with dementia, and 135 were classified as having CIND. RESULTS: ACE-R norms were
      provided with the sample stratified into age and education bands. ACE-R total
      scores varied significantly according to age, education, and sex. To distinguish
      CN from dementia, a cut-off of 64 points was established (sensitivity 91%,
      specificity 76%) and to differentiate CN from CIND the best cut-off was 69 points
      (sensitivity 73%, specificity 65%). Cut-off scores varied according to the
      educational level. CONCLUSIONS: This study offers normative and accuracy
      parameters for seniors with lower education and it should expand the use of the
      ACE-R for this population segment.

PMID- 28511736
TI  - Dietary salt intake in the Australian population.
AB  - OBJECTIVE: To update the estimate of mean salt intake for the Australian
      population made by the Australian Health Survey (AHS). DESIGN: A secondary
      analysis of the data collected in a cross-sectional survey was conducted.
      Estimates of salt intake were made in Lithgow using the 24 h diet recall
      methodology employed by the AHS as well as using 24 h urine collections. The data
      from the Lithgow sample were age- and sex-weighted, to provide estimates of daily
      salt intake for the Australian population based upon (i) the diet recall data and
      (ii) the 24 h urine samples. SETTING: Lithgow, New South Wales, Australia.
      SUBJECTS: Individuals aged >=20 years residing in Lithgow and listed on the 2009
      federal electoral roll. RESULTS: Mean (95 % CI) salt intake estimated from the 24
      h diet recalls was 6.4 (6.2, 6.7) g/d for the Lithgow population compared with a
      corresponding figure of 6.2 g/d for the Australian population derived from the
      AHS. The corresponding estimate of salt intake for Lithgow adults based upon the
      24 h urine collections was 9.0 (8.6, 9.4) g/d. When the age- and sex-specific
      estimates of salt intake obtained from the 24 h urine collections in the Lithgow
      sample were weighted using Australian census data, estimated salt intake for the
      Australian population was 9.0 (8.6, 9.5) g/d. Further adjustment for non-urinary
      Na excretion made the best estimate of daily salt intake for both Lithgow and
      Australia about 9.9 g/d. CONCLUSIONS: The dietary recall method used by the AHS
      likely substantially underestimated mean population salt consumption in
      Australia.

PMID- 28511737
TI  - Suicide in older adults: differences between the young-old, middle-old, and
      oldest old.
AB  - BACKGROUND: In the limited research into suicides in older adults, they have been
      treated as a homogenous group without distinguishing between different age
      groups. This study aimed to compare differences in sociodemographic variables,
      recent life events, and mental and physical illnesses between three age groups
      within older adults who died by suicide: young-old (65-74 years), middle-old (75
      84 years), and oldest old (85 years and over) in Queensland, Australia, during
      the years 2000-2012 (N = 978). METHODS: The Queensland Suicide Register was
      utilized for the analysis. Annual suicide rates were calculated. Odds ratios with
      95% confidence intervals and chi 2 tests for trend were calculated to examine
      differences between the three groups. RESULTS: Suicide rates were increasing with
      age for males, but not for females. Hanging and firearms were the predominant
      methods of suicides. However, suffocation by plastic bag and drowning as suicide
      methods increased with age, in contrast firearms and explosives decreased with
      age. Overall, psychiatric problems, suicidal behavior, legal and financial
      stressors, and relationship problems decreased significantly with age, meanwhile
      physical conditions and bereavement increased with age. CONCLUSION: Suicide
      across older adulthood is not a homogenous phenomenon. Our findings showed
      significant differences in the prevalence of potential risk factors within the
      three different age groups considered. To prevent suicide in older adults would
      require targeting specific factors for each subgroup while using holistic and
      comprehensive approaches.

PMID- 28511738
TI  - Positive psychology outcome measures for family caregivers of people living with
      dementia: a systematic review.
AB  - BACKGROUND: Family caregivers of people living with dementia can have both
      positive and negative experiences of caregiving. Despite this, existing outcome
      measures predominately focus on negative aspects of caregiving such as burden and
      depression. This review aimed to evaluate the development and psychometric
      properties of existing positive psychology measures for family caregivers of
      people living with dementia to determine their potential utility in research and
      practice. METHOD: A systematic review of positive psychology outcome measures for
      family caregivers of people with dementia was conducted. The databases searched
      were as follows: PsychINFO, CINAHL, MEDLINE, EMBASE, and PubMed. Scale
      development papers were subject to a quality assessment to appraise psychometric
      properties. RESULTS: Twelve positive outcome measures and six validation papers
      of these scales were identified. The emerging constructs of self-efficacy,
      spirituality, resilience, rewards, gain, and meaning are in line with positive
      psychology theory. CONCLUSIONS: There are some robust positive measures in
      existence for family caregivers of people living with dementia. However, lack of
      reporting of the psychometric properties hindered the quality assessment of some
      outcome measures identified in this review. Future research should aim to include
      positive outcome measures in interventional research to facilitate a greater
      understanding of the positive aspects of caregiving and how these contribute to
      well-being.

PMID- 28511739
TI  - Self-Critical Thinking and Overgeneralization in Depression and Eating Disorders:
      An Experimental Study.
AB  - BACKGROUND: Self-critical thinking is common across psychological disorders. This
      study hypothesized that it may play an important role in 'overgeneralization',
      the process of drawing general implications from an isolated negative experience.
      AIMS: To explore the impact of two experimental tasks designed to elicit self
      critical thoughts on the endorsement of general negative self-views of clinical
      and non-clinical populations. METHOD: Three groups (depression, eating disorders
      and non-clinical controls), completed standardized questionnaires and the two
      tasks. Participants rated their self-critical thinking and general negative self
      beliefs before and after each task. RESULTS: Following a failure experience, both
      clinical groups showed a greater increase in general negative self-views compared
      with controls, indicating greater overgeneralization. Both habitual and increases
      in state self-critical thinking were associated with overgeneralization while
      negative perfectionism was not. Overgeneralization was more strongly associated
      with post-task reduced mood than self-criticism. CONCLUSIONS: Self-critical
      thinking may be an important factor in the process of overgeneralization, and the
      increase in general negative self-views may be particularly crucial for lowering
      of mood.

PMID- 28511741
TI  - Influenza detection and prediction algorithms: comparative accuracy trial in
      Ostergotland county, Sweden, 2008-2012.
AB  - Methods for the detection of influenza epidemics and prediction of their progress
      have seldom been comparatively evaluated using prospective designs. This study
      aimed to perform a prospective comparative trial of algorithms for the detection
      and prediction of increased local influenza activity. Data on clinical influenza
      diagnoses recorded by physicians and syndromic data from a telenursing service
      were used. Five detection and three prediction algorithms previously evaluated in
      public health settings were calibrated and then evaluated over 3 years. When
      applied on diagnostic data, only detection using the Serfling regression method
      and prediction using the non-adaptive log-linear regression method showed
      acceptable performances during winter influenza seasons. For the syndromic data,
      none of the detection algorithms displayed a satisfactory performance, while non
      adaptive log-linear regression was the best performing prediction method. We
      conclude that evidence was found for that available algorithms for influenza
      detection and prediction display satisfactory performance when applied on local
      diagnostic data during winter influenza seasons. When applied on local syndromic
      data, the evaluated algorithms did not display consistent performance. Further
      evaluations and research on combination of methods of these types in public
      health information infrastructures for 'nowcasting' (integrated detection and
      prediction) of influenza activity are warranted.

PMID- 28511740
TI  - The association between cognitive decline and incident depressive symptoms in a
      sample of older Puerto Rican adults with diabetes.
AB  - BACKGROUND: Older Puerto Rican adults have particularly high risk of diabetes
      compared to the general US population. Diabetes is associated with both higher
      depressive symptoms and cognitive decline, but less is known about the
      longitudinal relationship between cognitive decline and incident depressive
      symptoms in those with diabetes. This study investigated the association between
      cognitive decline and incident depressive symptoms in older Puerto Rican adults
      with diabetes over a four-year period. METHODS: Households across Puerto Rico
      were visited to identify a population-based sample of adults aged 60 years and
      over for the Puerto Rican Elderly: Health Conditions study (PREHCO); 680
      participants with diabetes at baseline and no baseline cognitive impairment were
      included in analyses. Cognitive decline and depressive symptoms were measured
      using the Mini-Mental Caban (MMC) and Geriatric Depression Scale (GDS),
      respectively. We examined predictors of incident depressive symptoms (GDS >= 5 at
      follow-up but not baseline) and cognitive decline using regression modeling.
      RESULTS: In a covariate-adjusted logistic regression model, cognitive decline,
      female gender, and greater diabetes-related complications were each significantly
      associated with increased odds of incident depressive symptoms (p < 0.05). In a
      multiple regression model adjusted for covariates, incident depressive symptoms
      and older age were associated with greater cognitive decline, and higher
      education was related to less cognitive decline (p < 0.05). CONCLUSIONS: Incident
      depressive symptoms were more common for older Puerto Ricans with diabetes who
      also experienced cognitive decline. Efforts are needed to optimize diabetes
      management and monitor for depression and cognitive decline in this population.

PMID- 28511743
TI  - Health and Economic Burden of Skin Melanoma in Croatia - Cost-of-illness Study.
AB  - Melanoma incidence is increasing, especially in the younger population. The aim
      of this study was to investigate the cost of this disease in the Croatian
      population and to identify costs through types of care and types of costs. The
      secondary goal was to estimate the prevalence of certain types of melanoma (as
      well as staging distribution) and to connect each stage and its prevalence in
      Croatia to related costs. A cost-of-illness analysis was performed, mainly
      including direct costs (monitoring, drugs, primary health care services,
      hospitalizations, and diagnostics). The calculations were based on data collected
      from Sestre milosrdnice University Hospital Center in Zagreb and from Cancer
      Registry Data. The number of patients with melanoma was calculated using the
      Markov model for melanoma staging and 5-year survival. The estimated total
      prevalence of melanoma in 2011 in Croatia was 2,180. The total cost of melanoma
      was estimated to 1,063,488 EUR, with 46% used for hospitalization and
      chemotherapy, 10% for dermatoscopy, and the remaining 17% being monitoring costs.
      The average cost per patient was estimated to range between 98 and 4,333 EUR
      depending on the stage of the disease. The cost of melanoma in the adult
      population in Croatia in a one-year timeframe accounted for as much as 0.04% of
      the total Croatian national health care budget for 2011. Study findings indicate
      the need for a clear strategy to achieve regular screening in order to detect the
      disease at an early stage.

PMID- 28511742
TI  - Predictors for routine admission to paediatric intensive care for post
      supraglottoplasty laryngomalacia patients.
AB  - OBJECTIVES: Supraglottoplasty for the treatment of laryngomalacia has little
      current evidence regarding post-operative care. Our study aimed to: (1)
      retrospectively assess what proportion of patients required paediatric intensive
      care unit level of care; (2) identify pre-operative predictive factors common to
      these cases; and (3) report patient outcomes at six weeks' follow up. METHODS: A
      10-year retrospective case series analysis was conducted of all patients
      diagnosed with laryngomalacia and subsequently treated with supraglottoplasty.
      Paediatric intensive care unit level of care was defined as the need for
      intubation or tracheostomy, positive pressure ventilation, multiple doses of
      nebulised adrenaline, and oxygen dependency beyond 12 hours. RESULTS: Forty-two
      patients (19 males, 23 females) were identified; 28.5 per cent of cases met our
      criteria for paediatric intensive care unit level of care. A low pre-operative
      oxygen saturation was the only significant risk factor that predicted a future
      need for paediatric intensive care unit level of care (p = 0.0008). CONCLUSION:
      This is the first study published in the UK to suggest the importance of pre
      operative oxygen saturation as a predictor of a future need for paediatric
      intensive care unit level of care.

PMID- 28511744
TI  - Correlation of Antibodies against Desmogleins 1 and 3 with Indirect
      Immunofluorescence and Disease Activity in 72 Patients with Pemphigus Vulgaris.
AB  - The enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence
      (IIF) have both been used for testing of antibodies to desmogleins 1 and 3 (anti
      Dsg1 and anti-Dsg3) and for the serologic diagnosis of pemphigus. IIF values and
      antibody concentrations and profile do not always correlate with a specific
      clinical phenotype and with the disease activity. The purpose of the present
      study was to correlate the clinical phenotype of patients with pemphigus vulgaris
      (PV) and the disease activity with anti-Dsg1 and anti-Dsg3 antibodies and IIF
      titers. A total of 72 patients with PV underwent ELISA serum testing for the
      presence and titers of anti-Dsg1 and anti-Dsg3 and IIF which were correlated with
      the severity of the disease (evaluated using the Pemphigus Disease Area Index,
      PDAI), clinical phenotype, and clinical course. In 79.2% patients there was a
      perfect correlation between the clinical phenotype and antibody profiles; in
      20.8% patients, clinical features and antigenic findings were discordant. A
      statistically significant correlation was found between disease activity and a)
      anti-Dsg3 and anti-Dsg1 concentrations (Rho=0.679, P<0.001 and Rho=0.363, P=0.02,
      respectively) and b) IIF titers (Rho=0.426, P<0.01), as well between IIF titers
      and anti-Dsg3 and anti-Dsg1 antibodies (Rho=0.742, P<0.01 and Rho=0.372, P=0.02,
      respectively). This study supports the previous observations that the disease
      severity in most patients with pemphigus correlates with IIF titers, which in
      turn is determined by the quantities of Dsg1 and Dsg3 antibodies, as well as the
      previous observation that the clinical phenotype and antibody profile are not
      always in correlation.

PMID- 28511745
TI  - Lupus Band Test in Patients with Borderline Systemic Lupus Erythematosus with
      Discoid Lesions.
AB  - Patients with lupus erythematosus (LE) that have discoid lesions who fulfill the
      four diagnostic criteria of systemic lupus erythematosus (SLE) with only
      mucocutaneous findings and antinuclear antibody (ANA) positivity were classified
      as borderline SLE in the literature. Objective of this study was to determine the
      place of borderline SLE with discoid lesions on the LE spectrum according to the
      lupus band test (LBT). Lesional and sun-protected non-lesional (SPNL) skin LBTs
      of 94 patients with LE that had discoid lesions were retrospectively evaluated.
      Firstly, patients were divided into two main groups: discoid LE (DLE; group A)
      and SLE (Group B); three subgroups were then classified as DLE (Group A),
      borderline SLE (Group B1) and SLE (Group B2) using another method. Each group had
      its own comparisons. Immunoreactant (IR) deposition was observed on the lesional
      skin in all patients and on the SPNL skin in 42 (44.7%). In patients with
      borderline SLE, the deposition of IgM was lower on the lesional LBTs, whereas
      isolated IgG was higher than SLE; thus, it shows similarity with DLE.
      Additionally, it was also closer to DLE because of the low deposition of C3,
      multiple IRs, and a double conjugate of IRs on the SPNL skin. However, it showed
      similarity with SLE in the high percentage of LBT positivity and more
      immunoglobulin M (IgM) and immunoglobulin G (IgG) deposition on the SPNL skin.
      The deposition of multiple conjugates on SPNL skin in patients with LE with
      discoid lesions may reflect systemic involvement. Despite the fact that LBT
      positivity on SPNL skin in borderline SLE was higher than DLE, less deposition of
      multiple conjugates compared to SLE indicates that the classification of
      borderline SLE with discoid lesions in the LE spectrum is questionable.

PMID- 28511746
TI  - Two Ultrasonographic Patterns in Maculopapular Cutaneous Mastocytosis: A
      Preliminary Report.
AB  - Maculopapular cutaneous mastocytosis (MPCM) is a variant of cutaneous
      mastocytosis resulting from abnormal accumulation of mast cells in dermal
      tissues. Ultrasonography is a contemporary, safe, non-invasive, and real-time
      diagnostic method. High-frequency ultrasonography (HFUS) utilizes probes emitting
      frequencies of 20 MHz and higher, visualizing and measuring areas of healthy and
      lesional skin in various dermatologic conditions. We examined 4 patients with
      MPCM using a taberna pro medicumTM (Germany) device. We present 2 characteristic
      ultrasonographic patterns of MPCM lesions. Three subjects presented with an
      abnormal, widened, and hypoechogenic area representing the dermis. One subject
      demonstrated an anechogenic fusiform structure below the epidermis that
      represented a localized pattern of infiltrate. This patient responded better to
      psoralen and ultraviolet A radiation (PUVA) therapy than the other subjects. Our
      research implies that HFUS may be used as an additional method in evaluating skin
      lesions in MPCM.

PMID- 28511747
TI  - Red Blood Cell Distribution Width is a Reliable Marker of Inflammation in Plaque
      Psoriasis.
AB  - Psoriasis is a systemic inflammatory disease accepted as an independent risk
      factor for cardiovascular diseases (CVD). Elevated levels and correlation of red
      cell distribution width (RDW) with inflammatory markers has recently been shown
      in studies investigating CVD risk and prognosis in rheumatoid arthritis and
      ankylosing spondylitis. The aim of this study was to evaluate levels and
      correlation of RDW with inflammatory markers in patients with plaque psoriasis.
      Data including demographics, disease severity indices, laboratory parameters, and
      bioelectrical impedance analysis was collected from medical charts of patients
      who were diagnosed with plaque psoriasis at the Hacettepe University Department
      of Dermatology between March 2014 and August 2015. Patients were evaluated for
      major CVD risk factors defined by international guidelines. 199 patients with
      psoriasis and 73 volunteers were included. Patients had statistically significant
      higher values of metabolic age, visceral fat rating, body-mass index (BMI), red
      blood cells (RBC), white blood cells (WBC), red blood cell distribution width
      (RDW), alanine aminotransferase (ALT), uric acid, low-density lipoprotein (LDL),
      and C-reactive protein (CRP) (p=0.044, p=0.047,p=0.029, p= 0.005, p=0.02, p<0,01,
      p=0.001, p=0,016, p=0,014, p<0.01). A statistically significant relationship and
      positive correlation between RDW and CRP levels was found in the patient group
      (p=0.01, r=0.396). Patients without major CVD risk factors (n=79) had
      significantly higher values of RDW, LDL, and CRP (p=0.01, p=0.031, p=0.03,
      respectively). Patients with psoriasis who had one or more CVD risk factors
      (n=120) had significantly higher values of BMI, RDW, thrombocytes, ALT, and CRP
      (p=0.038, p=0.01, p=0.017, p=0.02, p=0.01, respectively). RDW, which is elevated
      as well as CRP, reflects the systemic inflammatory burden and can be used for
      prediction of CVD in psoriasis. In fact, patients with psoriasis who do not have
      any major CVD risk factors still have high levels of CRP and RDW, supporting the
      hypothesis that psoriatic inflammation itself can simultaneously cause CRP and
      RDW elevation. Coexistence of CVD risk factors is associated with ALT elevation
      since additional CVD risk factors may predict psoriatic comorbidities such as non
      alcoholic fatty liver disease.

PMID- 28511748
TI  - Stress and Coping in Patients with Clinical Manifestations of Human
      Papillomavirus.
AB  - Stressful life events in response to a psychosocial trigger have been reported to
      negatively affect the course of infections. This study was based on patients with
      clinical manifestations of human papillomavirus (HPV) infection and a control
      group of patients with psoriasis who were admitted over a period of one year to
      the Dermatology Department of Karlovac General Hospital. A total of 122 patients
      participated in the study, either with a confirmed diagnosis of clinical
      manifestations of HPV infection (n=66) or in a psoriasis control group (n=56).
      The aim of this study was to determine which coping strategies are used in
      patients with clinical manifestations of HPV infection. We used the Recent Life
      Changes Questionnaire and Brief COPE test for stress evaluation. There were no
      statically significant differences between adaptive and maladaptive coping
      strategies comparing patients with HPV and a control group. The difference in
      specific coping strategies between HPV and control groups showed that self-blame
      and planning strategies were statistically significantly more common in the HPV
      group. Patients with HPV with genital warts used maladaptive coping statistically
      significantly more than patients with non-genital localization of HPV. Patients
      with HPV who had a higher score of life stress events used maladaptive coping
      statistically significantly more than patients with a lower life stress events
      score. The results point to the need for patients with HPV with genital
      localization and high numbers of stress events to learn how to cope with stress,
      enabling them to take action and change their ways of coping. There is also a
      need to integrate psychological intervention into standard care protocols of
      dermatologic diseases.

PMID- 28511749
TI  - Microinvasive Radial Growth Phase of Cutaneous Melanoma: A Histopathological and
      Immunohistochemical Study with Diagnostic Implications.
AB  - Cutaneous melanoma (M) can develop through two progression phases: the radial
      growth phase of M (RGPM) and the vertical one. This distinction has a practical
      relevance in defining lesions with potential for a metastatic course. We analyzed
      the morphological attributes (intraepidermal proliferation type, inflammatory
      infiltrate, mitogenicity, Breslow thickness, Clark level, ulceration) and the
      immunohistochemical profile (S100, Melan A, HMB45, p16INK4a, CD117, Ki67, Cyclin
      D1, E Cadherin, Podoplanin) of 12 microinvasive RGPMs in absence of regression,
      with almost 10 years of follow-up. Immunohistochemistry (IHC) revealed that S100,
      Melan A, and HMB45 maintain a high expression in M cells in both epidermal and
      dermal compartments. Interestingly, an overexpression of p16INK4a in the nests of
      dermal microinvasion has been ascertained in all our cases. On the other hand, we
      found an attenuation of expression for CD117, Ki67, Cyclin D1, and E Cadherin in
      the migration phase from the epidermis to dermis. Each phase in M progression
      appears characterized by a specific immunohistochemical profile, as a result of
      molecular alterations. The long-term follow-up of our case series showed that
      microinvasive RGPM without regression is not tumorigenic and is devoid of
      metastatic potential; therefore, its accurate categorization is important.
      Conversely, microinvasive RGPM with regression should be classified as
      melanocytic tumor with uncertain biological potential. IHC for p16INK4a can be
      helpful in the diagnosis of microinvasive M on challenging cutaneous biopsies.
      Moreover, it can be applied as an immunohistochemical discriminator to
      distinguish microinvasive RGPM from in situ RGPM and microinvasive RGPM from
      dysplastic nevi.

PMID- 28511750
TI  - The Prevalence of Penile Pearly Papules among Young Men.
AB  - The aim of this study was to determine the prevalence of pearly penile papules
      (PPP) among young men in Eskisehir, Turkey. This was a prospective, non
      randomized, cross-sectional study. From December 2014 to September 2015, 2613
      consecutive male patients who were referred to the dermatology outpatient clinic
      were included in the study. Patients were inspected for the presence of PPP,
      localization, and association with human papilloma virus (HPV). A total of 2613
      patients were included in the study. The average age of the patients was 21.33+/
      2.08 (mean +/- Standard Deviation (SD); ranging from 18 to 24) years. All of the
      patients were white and circumcised men. Of the 2613 patients, 449 (17.18%) PPP
      were observed. PPP were localized on the corona of the glans penis (100%),
      coronal sulcus (18.9%), frenulum (15.1%), ventral shaft (5.3%), and dorsal shaft
      of the penis (2.4%). Of the 449 patients with PPP, 23 (5.3%) underwent treatment;
      73 (16.2%) would consider removal, 7 (1.5%) had a previous treatment for HPV, and
      5 (1.1%) had HPV. PPP are encountered very commonly in the pubertal age in boys
      and young men. All medical practitioners should be familiar with PPP. Their
      similarity to genital warts may generate a false apprehension of venereal disease
      and may lead to unwanted and hazardous treatments. Therefore, better health
      education is needed.

PMID- 28511751
TI  - Aging - What Do We Know?
AB  - Skin aging is a combination of reduction in the biological activity of cells, a
      slowing down of regenerative processes, and a loss of resistance to environmental
      factors. Genetics, lifestyle, and hormones significantly affect proper
      functioning of the skin. The aim of this article was to present the current
      knowledge about aging processes and concurrent therapies which can influence skin
      aging.

PMID- 28511752
TI  - Biosimilars: An Update on Clinical Trials (Review of Published and Ongoing
      Studies).
AB  - Biosimilars represent a new trend in the treatment of many immune-mediated
      inflammatory diseases. Regulatory requirements for approval of biosimilars are
      different from those of originators and rely mostly on the evidence generated
      from bioequivalence studies and in particular from RCTs. Our goal in this review
      was to search for relevant studies from randomized controlled trials on the
      biosimilars adalimumab, etanercept, infliximab and ustekinumab compared with
      their reference medication (publication in Medline) and ongoing studies in
      clinical trial registries. For infliximab biosimilars, we found data on patients
      with ankylosing spondylitis rheumatoid arthritis indicating no clinically
      relevant differences regarding efficacy and safety, as well as data on
      inflammatory bowel diseases and psoriasis. In addition, three registered studies
      of adalimumab biosimilars and just one study of an etanercept biosimilar were
      being carried out in patients with psoriasis. Ongoing studies on adalimumab,
      etanercept, and infliximab biosimilars in patients with rheumatoid arthritis were
      also identified. The conclusion seems to be that there are only 4 clinical trials
      on psoriasis (3 for the adalimumab biosimilar and 1 for etanercept biosimilar)
      and 1 clinical trial for Pso, CD, UC, RA, and AS (with the Infliximab
      biosimilar). Thus, the real and unique advantage of biosimilars is the low price
      derived from the special design studies despite the high technology used in
      fabrication process. Although not all ongoing biosimilar trials may have been
      registered, the present situation in terms of registered trials is quite
      unsatisfactory and provision of further clinical data and inclusion of patients
      in patient registries will be crucial.

PMID- 28511754
TI  - Antibiotic-induced Toxic Epidermal Necrolysis - A Case Report.
AB  - Toxic epidermal necrolysis (TEN) is severe cutaneous hypersensitivity reaction
      characterized by necrosis of the epidermis and detachment of the epidermis and
      dermis that usually occurs as an idiosyncratic reaction to certain drugs. We
      report the case of a patient admitted to our Intensive Care Unit after an above
      the-knee amputation who developed toxic epidermal necrolysis, possibly resulting
      from antibiotics therapy. Therapy included a combination of intravenous
      immunoglobulin with gentle early debridement of necrotic skin areas followed by
      wound coverage with a synthetic cover (Aquacel Ag(r)). This case report suggests
      that intensive wound management together with intravenous immunoglobulin might be
      beneficial in the treatment of patients with TEN.

PMID- 28511753
TI  - Mycobacterium marinum Infection of the Hand in an Immunocompromised Aquarium
      Hobbyist.
AB  - M. marinum, a nontuberculous mycobacterium, is a rare human pathogen widely
      distributed in the aquatic environment. In the previous century, epidemics took
      place due to inadequately chlorinated swimming pool water. Nowadays the majority
      of infections are acquired through contact of previously damaged skin with
      contaminated fish tank water. We present a case of M. marinum infection of the
      hand in an aquarium hobbyist which stayed unrecognized for 2 years. After
      confirming the correct diagnosis, the patient was successfully treated with a
      regiment containing clarithromycin and rifampicin. The aim of this paper is to
      raise the awareness of the possibility of M. marinum infection when encountered
      with non-healing nodular/verrucous/ulcerative lesions of the extremities.

PMID- 28511755
TI  - Onychomadesis Following Cutaneous Vasculitis.
AB  - Beau lines are transverse, band-like depressions extending from one lateral edge
      of the nail to the other and affecting all nails at corresponding levels (1).
      Onychomadesis is considered an extreme form of Beau line with subsequent
      separation of the proximal nail plate from the nail bed. Both fall along a
      spectrum of nail plate abnormalities that occur secondary to temporary nail
      matrix arrest (NMA). Various systemic and dermatologic conditions have been
      reported in association with onychomadesis (2-7) (Table 1). Nail changes can
      affect all or some of the nails and both the fingernails and toenails; however,
      fingernails are more frequently affected. The severity of the nail changes varies
      depending on the underlying cause, its duration, and environmental factors (8).
      We present a case of onychomadesis following cutaneous leukocytoclastic
      vasculitis (CLCV). A 61-year-old woman presented to the Dermatology Clinic
      complaining of a purpuric rash that began on her lower extremities and rapidly
      progressed to her abdomen and upper extremities over the previous five days. Her
      medical history was remarkable for hypertension and diet-controlled diabetes
      mellitus. Her medications included enalapril, which she had been taking for the
      past four years. On three consecutive days before the skin eruption, the patient
      took oral diclofenac sodium for hip pain. A clinical examination revealed non
      blanching petechial rash on the legs, abdomen, and upper limbs up to the elbow
      (Figure 1, A) with leukocytoclastic vasculitis on biopsy (Figure 1, B). Direct
      immunofluorescence was negative. Laboratory investigations revealed a white blood
      cell count of 14.5 * 109/L with a normal differential count, and a platelet count
      of 380 * 109/L. Westergren erythrocyte sedimentation rate was 65 mm/1st h, and C
      reactive protein was at 8.5 mg/dL. Antinuclear antibodies, rheumatoid factor,
      immune complexes, and cryoglobulinemia were negative, as were B and C hepatitis
      virus serological tests. Her renal, cardiac, pulmonary, and abdominal exams were
      normal. Diclofenac was discontinued due to a clinical suspicion of drug-induced
      cutaneous vasculitis. The rash resolved in 2 weeks without treatment, leaving
      post-inflammatory hyperpigmentation. Four weeks later, she presented with
      painless, palpable grooves on all 10 fingernails (Figure 2). The grooves were 3
      to 4 mm in width, at a similar distance from the proximal nail fold. There were
      no signs of periungual inflammation. The patient denied any recent history of
      trauma, unusual activities, or chemical exposure. Routine serum biochemistry and
      hematology results were normal. Repeated potassium hydroxide preparations and
      fungal cultures of the nail clippings were negative. A diagnosis of Beau lines
      and onychomadesis was made. Nail changes were tolerable and did not require any
      specific treatment. During the follow up, the Beau lines advanced with the linear
      growth of the nails and disappeared (Figure 3 and 4). Four fingernails developed
      complete nail shedding (onychomadesis). No toenail alterations were observed in
      this period. A complete recovery of the nail plate surface was observed after 4
      months. The nail matrix epithelium is formed by highly proliferating cells that
      differentiate and keratinize to produce the nail plate. The nail matrix
      epithelium is very susceptible to toxic noxae, and acute damage results in a
      defective nail plate formation. Nail matrix arrest is a term used to describe a
      temporary inhibition of the nail matrix proliferation that can present as Beau
      lines and onychomadesis (8). The width of Beau lines relates to the duration of
      the etiological agent. As the nail adheres firmly to the nail bed, the
      onychomadesis remains latent for several weeks before leading to temporary
      shedding (8,9). There are several proposed etiological mechanisms for NMA. NMA
      associated with fever, severe infection, and major medical illnesses can be
      explained by an inflammation of the matrix, periungual tissues, or digital blood
      vessels (8); chemotherapy agents temporary inhibit the mitotic activity in nail
      matrix (10); the detection of Coxackie virus in the shedding nail particle,
      following hand, foot, and mouth disease, suggests that the viral replication
      itself may directly damage the nail matrix (11). However, as nail changes are not
      unique, it may be difficult to incriminate a single etiological agent. Our
      patient presented with an onset of Beau lines seven weeks after the initial CLCV
      lesions, which suggests that vasculitis might have acted as a trigger for NMA. As
      the fingers were not affected by CLCV, an indirect effect of vasculitis is more
      plausible. Leukocytoclastic vasculitis is a small-vessel inflammatory disease
      mediated by a deposition of immune complexes. Thus, the circulating immune
      complexes may be involved in the damage of nail bed microvasculature. Considering
      that the patient had been receiving enalapril and diclofenac, it is less likely
      that those drugs were involved in the pathogenesis of NMA. Enalapril was
      continued, and the nail changes were resolved while patient was still on
      enalapril. Furthermore, diclofenac is a widely prescribed drug and its
      association with NMA is yet to be described in literature. We described a patient
      who developed Beau lines and onychomadesis following cutaneous leukocytoclastic
      vasculitis. This clinical observation can expand the spectrum of possible causes
      of nail matrix arrest.

PMID- 28511756
TI  - Nested Melanoma, a New Morphological Variant of Superficial Spreading Melanoma
      with Characteristic Dermoscopic Features.
AB  - A new morphological variant of superficial spreading melanoma (SSM) was first
      described by Kutzner et al. (1) and named "melanoma composed exclusively or
      predominantly of large nests"; it was later named "nested melanoma" (NM) (2,3).
      Clinically, lesions are larger in diameter (>6 mm), mostly showing typical
      clinical features of melanoma (the ABCD rule), and significantly different from
      all other pigmented lesions (the "ugly duckling sign") (1). The majority of NM is
      found on the trunk and limbs of patients older than 60 years (1-9). Dermoscopy
      shows typical features of melanoma (asymmetry, irregular blotches, atypical
      pigmented network, multicomponent structure, irregular dots, and globules)
      followed by the "typical" dermoscopic finding of a globular pattern with globules
      varying in shape, color, and distribution (1,3). It is known that flat nevi in
      the elderly present with a reticular or structureless dermoscopic global pattern,
      along with the fact that total nevi count decreases with advancing age due to
      involution of nevi (4,5). Therefore, a globular pattern is uncommon in the
      elderly, and this finding should always invoke a high suspicion of melanoma.
      Histological diagnosis may be difficult because of the predominantly nested
      pattern, and the condition may be confused histologically with a benign
      junctional nevus (6). However, these large junctional nests of different sizes,
      with bridging and cytonuclear atypias together with lesion asymmetry, are the
      hallmark of this special kind of melanoma (6). Pathologically, NM presents with
      large intraepidermal melanocytic nests, which are more or less the same size and
      shape and equally distributed along the dermoepidermal junction, with a focal
      tendency to confluence. Melanocytes in nests show moderate to significant
      cytological atypia (1). Since most NMs were found on sun-damaged skin, solar
      elastosis can be present. Pagetoid spread of atypical melanocytes along the
      epidermis is rare, but may be found (1-3). In most case reports there was
      discrepancy between clinical and dermoscopic features - both favoring melanoma -
      and histopathology, which at first glance appeared nevoid (9). Although the
      majority of analyzed NMs were in situ, an invasive dermal component was also
      found. The atypical nevus in the elderly is an unstable nevus, and one variation
      also observed is the hypercellular nested variant described by authors; these
      have been reported as in situ nevoid melanomas, with cellular morphology usually
      associated with crowded small-to-medium hyperchromatic melanocytes. The
      progression of these atypical nested melanomas is often to a small cell (nevoid)
      melanoma, which may become desmoplastic (9). Although the term "superficial
      spreading melanoma" is appropriate for NM from a clinical perspective, at least
      some of these tumors may be linked to an aberrant nevus pathway seen in elderly
      individuals, explaining their unusual pattern resembling a bizarre nevus (9).
      Additional tests can be performed due to clinicopathological discrepancy,
      including confocal microscopy, immunohistochemistry, array comparative genomic
      hybridization (aCGH), and in situ hybridization (FISH). Reflectance confocal
      microscopy may be useful in cases of such difficult lesions in order to proceed
      to surgical excision with more confidence, and can reveal the presence of dense
      nests at the dermo-epidermal junction with cytologic atypia and pagetoid cells
      (3,7). In confocal microscopy, a grossly regular clod pattern (at low
      magnification) with atypical cells within nests (at higher magnification) was
      found if the NM was in situ (3,7,9). aCGH showed multiple chromosomal aberrations
      in all cases (1,2). Processing with the FISH technique showed a variation in
      range from 40% to 87% FISH-positive NM, depending on different authors (1,2).
      Once the diagnosis of NM is established, further treatment, including re
      excision, is highly recommended (2). All the authors who described NM consider NM
      a special variant of SSM in the elderly, and according to their opinion this
      should lead to modification of histopathological criteria for SSM. We would
      stress that the "elderly" criterion is not mandatory given the numerous cases
      reported in people under 60 years of age (6). This is important and should
      henceforth reduce misinterpretation of this variant of melanoma due to the
      lesion's nevoid appearance (9). Dermoscopic criteria for NM should also be
      established so clinicians consider NM in differential diagnosis, which would
      further help the pathologist establish the correct diagnosis, since it is crucial
      not to misdiagnose a malignant lesion. Dermoscopy is very helpful in all cases,
      and globules are typically found in conjunction with other melanoma-specific
      criteria (1,3).

PMID- 28511757
TI  - Telehealth Overview: The Reality Check, Please.
AB  - The trend lines and bar charts are marching up. Investors are investing, insurers
      are extending coverage, health care systems are getting on board. But there at
      some skunks at the telehealth garden party: research suggesting quality and
      utilization problems and lingering uncertainty about reimbursement.

PMID- 28511758
TI  - Possible Employee Wariness Stifles Telehealth's Acceptance.
AB  - A lot hinges on this question: Do you feel comfortable getting a diagnosis or
      being treated for a condition by someone on a screen?

PMID- 28511759
TI  - Telehealth Business: Boom Times, but Profits May Wait.
AB  - Investors are plowing millions into telehealth startups. Millennials could be
      eager adopters. But these at early times and it may take years--and some
      regulatory changes--for profits to materialize.

PMID- 28511760
TI  - Some Thumbs Up, Some Down, on Telehealth Quality of Care.
AB  - The study results are a mishmash; the methods, a work in progress. Antibiotic
      prescribing is a trouble spot.

PMID- 28511761
TI  - 'Telemental' Health Is Becoming the Norm.
AB  - When it's time for a session, your therapist's face is on your phone or computer
      instead of in the room. Telemental health doesn't mean the end of in-person
      sessions, but it's increasingly part of the therapy mix.

PMID- 28511762
TI  - Q&A: A Conversation with Henry DePhilips, MD: The Doctor in the Teladoc House.
AB  - The CMO of Teladoc, one of the country's largest telemedicine providers,
      certainly knows how to sing the praises of the industry, and handle devil's
      advocate kind of questions as well. Most of Teledoc's customers are commercial
      insurers and employers. Medicare? Not so much. Medicaid makes "perfect sense."

PMID- 28511763
TI  - Are Insurers' Prior Authorization Rules Killing Opioid Addicts?
AB  - Some insurers are changing their rules after the AMA and others said prior
      authorization could result in treatment delays that can be deadly.

PMID- 28511765
TI  - Basaglar, an Insulin 'Follow On,' Prepares To Do Battle With Lantus.
AB  - At last, there's a biosimilar-like competitor in the U.S. insulin market. Can
      Basaglar put some downward pressure on prices?

PMID- 28511764
TI  - Telehealth Wave: Surf's Up for Fed, State Policymakers.
AB  - If millions of Americans lose Medicaid or private health insurance coverage
      because of the unACAing of American health care, telehealth may seem like a
      gimmicky sideshow rather than a good-faith effort to bring health care into the
      digital century.

PMID- 28511766
TI  - Medimedia Poll of Managed Care Readers: Telehealth Gets a Warm Reception.
AB  - In an online survey conducted in late February and early March, 37% of the 174
      respondents rated the likelihood that telehealth will reduce health care costs as
      high, and 50% favored laws and regulations that would encourage its adoption.

PMID- 28511767
TI  - Finding the Virtue in Virtual Care.
AB  - Virtual care offerings come with no shortage of complexities, but their potential
      for value has many asking when, not if, to invest.

PMID- 28511768
TI  - Telemedicine Seems To Work But Payment Creates a Disconnect.
AB  - The cost savings go to payers, but providers often wind up footing the bill.
      Value-based care could solve the problem.

PMID- 28511770
TI  - Federal Per Capita Funding of Medicaid Deals a Wild Card to the States.
AB  - Republicans say it brings efficiency and flexibility. Others see dire
      consequences for beneficiaries.

PMID- 28511771
TI  - Multiple priming instances increase the impact of practice-based but not verbal
      code-based stimulus-response associations.
AB  - Stimulus-response (S-R) associations, the basis of learning and behavioral
      automaticity, are formed by the (repeated) co-occurrence of stimuli and responses
      and render stimuli able to automatically trigger associated responses. The
      strength and behavioral impact of these S-R associations increases with the
      number of priming instances (i.e., practice). Here we investigated whether
      multiple priming instances of a special form of instruction, verbal coding, also
      lead to the formation of stronger S-R associations in comparison to a single
      instance of priming. Participants either actively classified stimuli or passively
      attended to verbal codes denoting responses once or four times before S-R
      associations were probed. We found that whereas S-R associations formed on the
      basis of active task execution (i.e., practice) were strengthened by multiple
      priming instances, S-R associations formed on the basis of verbal codes (i.e.,
      instruction) did not benefit from additional priming instances. These findings
      indicate difference in the mechanisms underlying the encoding and/or retrieval of
      previously executed and verbally coded S-R associations.

PMID- 28511773
TI  - Psychiatric Patient Length of Stay in the Emergency Department Following Closure
      of a Public Psychiatric Hospital.
AB  - BACKGROUND: Psychiatric patient boarding in the emergency department (ED) is a
      ubiquitous problem associated with increased morbidity and mortality. OBJECTIVE:
      We evaluate the effect of closing a public psychiatric facility in a major
      metropolitan area on the ED length of stay (LOS) of psychiatric patients.
      METHODS: This was a retrospective chart review at two metropolitan EDs of all
      patients assessed to require inpatient psychiatric hospitalization. The time of
      arrival, time of disposition, time of transfer, insurance status, and accepting
      facility type were collected prior to and following the closure of a local
      inpatient psychiatric facility. RESULTS: We analyzed a total of 1107 patients
      requiring inpatient psychiatric hospitalization, with 671 patients who presented
      prior to the closure of the closest public psychiatric facility and 436 patients
      that presented following the facility closure. Following hospital closure,
      patients with private insurance (620 min before, 771 min after) and
      Medicare/Medicaid (642 min before, 718 min after) had statistically significantly
      longer ED LOS, as well as patients transferred to a private psychiatric hospital
      (664 min prior, 745 min after). However, overall ED length of stay following
      hospital closure for transfer of all psychiatric patients requiring inpatient
      hospitalization was not found to be statistically significant (1017 min prior,
      967 min after). CONCLUSION: There was a statistically significant increase in ED
      LOS for patients with private insurance, Medicare/Medicaid, and for those
      patients transferred to a private psychiatric facility following closure of a
      public mental health hospital; however, overall, ED LOS was not increased for
      patients transferred to an inpatient psychiatric facility. This study highlights
      the significant impact that the closure of a single inpatient psychiatric
      facility can have on nearby EDs. We hope to bring attention to the need for
      increased psychiatric services during a time when there is a nationwide trend
      toward the reduction of available inpatient psychiatric beds.

PMID- 28511774
TI  - An Unusual Case of Flank Pain: More Than Just an Inguinal Hernia.

PMID- 28511772
TI  - Transcoronary Concentration Gradient of microRNA-133a and Outcome in Patients
      With Coronary Artery Disease.
AB  - Circulating levels of microRNA (miR)-133a are increased in patients with coronary
      atherosclerotic disease (CAD). Whether the cardiac release of this miR provides
      any prognostic information in patients with CAD is currently unknown. We aimed to
      investigate if changes in concentration of miR-133a trough the coronary
      circulation may be associated with patients' cardiovascular outcome. We enrolled
      111 patients (82 with stable CAD and 29 with acute coronary syndromes [ACS]) who
      underwent coronary angiography. Circulating levels of miR-133a were measured
      across the transcoronary circulation. Major adverse cardiac events (MACE: death,
      nonfatal myocardial infarction, and need for revascularization) were recorded
      through a median follow-up of 32 months. An increased transcoronary concentration
      gradient of miR133a showed a significant association with overall rate of MACE at
      follow-up in patients with both stable CAD and ACS (p = 0.011 and p = 0.002,
      respectively). At the single end point-analysis, increased transcoronary
      concentration gradients of miR133a were significantly associated with increased
      rate of death in patients with ACS (p = 0.017) and with increased incidence of
      new revascularization because of in-stent restenosis in patients with stable CAD
      (p = 0.026). Kaplan-Meier curves showed a significantly worse event-free survival
      in patients with greater transcoronary gradients of miR133a (p = 0.026 in stable
      CAD group and p = 0.007 for ACS group). Nevertheless, these findings lost their
      significance after adjustment for common cardiovascular risk factor and high
      sensitivity troponin-T. In conclusions, the release of miR133a, as measured by
      its transcoronary concentration gradient, is associated with a higher incidence
      of MACE in patients with CAD, but it does not add significant prognostic
      information compared with traditional prognostic biomarkers, therefore limiting
      its potential usefulness in the clinical practice. Nevertheless, the differential
      modulation of miR-133a release in the coronary circulation may reflect
      pathophysiological mechanism involved in CAD progression and complications and
      suggest a novel potential role for this miR in the development of in-stent
      restenosis.

PMID- 28511775
TI  - Alpha-fetoprotein is a significant prognostic factor for gastric cancer: Results
      from a propensity score matching analysis after curative resection.
AB  - BACKGROUND: Prognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC)
      remains elusive so far due to disparities in cohort size and baseline
      characteristics in previous studies. A propensity score matching (PSM) analysis
      as well as multivariable model was performed for unbiased evaluation of the
      outcome in AFPGC. METHODS: Among 3034 gastric cancer patients who underwent
      curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea
      between 2002 and 2007, we identified 97 patients being positive for AFP either by
      elevation of serum-AFP levels >10 MUg/L or by immunohistochemical staining. Due
      to marked disparities in baseline characteristics and cohort size, propensity
      score-matching was performed which matched 87 AFPP-GC patients to the same number
      of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were
      compared using chi2-test. Survival curves were compared using the Kaplan-Meier
      method and multivariable regression analysis was performed to evaluate the effect
      of AFP-positivity while adjusting the effects of confounding variables. RESULTS:
      AFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts.
      After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location,
      grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren
      histologic type and stage distribution. In multivariable regression analysis of
      the PSM-groups, only AFP-positivity and pathologic stage were predictive for
      overall survival (HR 2.98, CI 95% {1.7-5.1}, p < 0.0001). Five-year-survival
      rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014).
      Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003).
      CONCLUSION: AFP can be considered as an independent negative predictor of overall
      and recurrence-free survival in patients with gastric cancer.

PMID- 28511776
TI  - Radiation-induced cancer risk predictions in proton and heavy ion radiotherapy.

PMID- 28511777
TI  - Expression of interleukin-1beta and interleukin-6 in leprosy reactions in
      patients with human immunodeficiency virus coinfection.
AB  - Previous studies suggest that coinfection of leprosy and human immunodeficiency
      virus (HIV) does not decrease the frequency and intensity of leprosy reactions.
      However, the immunological aspects of leprosy reactions in coinfected patients
      remain obscure, with a limited number of studies showing contradictory results.
      Observational study using tissue samples collected during leprosy reactions from
      15 patients coinfected with leprosy and HIV and from 15 patients with leprosy
      alone. Patients were part of a prior larger cohort study of leprosy patients with
      and without HIV coinfection. Specific antibodies were used to detect IL-1beta and
      IL-6 expression in skin biopsy tissue cells. IL-1beta and IL-6 expression was
      similar between leprosy patients with and without HIV coinfection (p>0.05).
      Coinfected and non-coinfected tissues showed similar levels of IL-1beta and IL-6
      expression for type 1 reactions. A trend towards increased levels of IL-1beta and
      IL-6 expression was observed in tissue from coinfected patients (p=0.0024). The
      expression of IL-1beta and IL-6 during leprosy reactions did not differ
      significantly between tissues obtained from leprosy patients with and without HIV
      coinfection. Therefore, we conclude that HIV coinfection does not affect the
      immunological pattern of leprosy reactions.

PMID- 28511778
TI  - Elevated cranial ultrasound resistive indices are associated with improved
      neurodevelopmental outcomes one year after pediatric cardiac surgery: A single
      center pilot study.
AB  - OBJECTIVE: To determine if a non-invasive, repeatable test can be used to predict
      neurodevelopmental outcomes in patients with congenital heart disease. METHODS:
      This was a prospective study of pediatric patients less than two months of age
      undergoing congenital heart surgery at the Children's Health Children's Medical
      Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized
      during the surgery, and ultrasound (US) resistive indices (RI) of the major
      cranial vessels were obtained prior to surgery, immediately post-operatively, and
      prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to
      z transformation were used where appropriate. RESULTS: A total of 16 patients
      were enrolled. All had US data. Of the sixteen patients, two died prior to the
      neurodevelopmental testing, six did not return for the neurodevelopmental
      testing, and eight patients completed the neurodevelopmental testing. There were
      no significant correlations between the prior to surgery and prior to discharge
      US RI and neurodevelopmental outcomes. The immediate post-operative US RI
      demonstrated a strong positive correlation with standardized neurodevelopmental
      outcome measures. We were able to demonstrate qualitative differences using
      multichannel NIRS during surgery, but experienced significant technical
      difficulties implementing consistent monitoring. CONCLUSIONS: A higher resistive
      index in the major cerebral blood vessels following cardiac surgery in the
      neonatal period is associated with improved neurological outcomes one year after
      surgery. Obtaining an ultrasound with resistive indices of the major cerebral
      vessels prior to and after surgery may yield information that is predictive of
      neurodevelopmental outcomes.

PMID- 28511779
TI  - An Evidence-based Review of the Efficacy of Treatment Approaches for Immature
      Permanent Teeth with Pulp Necrosis.
AB  - INTRODUCTION: Two fundamental assumptions for teeth treated with regenerative
      endodontic procedures (REPs) are (1) that the clinical outcome is comparable with
      the traditional techniques of calcium hydroxide apexification and mineral
      trioxide aggregate apical barrier techniques and (2) that REPs will result in
      further root maturation. METHODS: A systematic review of the electronic databases
      (Scopus, PubMed, and Web of Science) involved a search for studies that used
      quantitative assessments of root maturation. The search terms were "dental pulp,"
      "regenerative endodontic therapy," "revascularization," and "revitalization." The
      identified studies were further screened for cohort studies that compared
      clinical outcomes between teeth treated with REPs and apexification/apical
      barrier approaches. The primary question under review was framed according to the
      population, exposure, and outcome format. RESULTS: Of the 368 studies identified
      by the search, 6 cohort studies used quantitative assessments of any further root
      maturation after REPs, and a subset of 4 of these cohort studies assessed and
      compared clinical outcomes between the different treatment approaches.
      CONCLUSIONS: Immature teeth with pulp necrosis treated with REPs generally show
      further root maturation although the results are variable. Clinical outcomes were
      similar for both groups. Patient-based criteria such as tooth discoloration,
      indications for changing the treatment option, and number of treatment
      appointments are all important for discussion before electing the appropriate
      treatment plan for the management of immature teeth with pulp necrosis.

PMID- 28511780
TI  - Anti-Mycobacterium avium complex activity of clarithromycin, rifampin, rifabutin,
      and ethambutol in combination with adenosine 5'-triphosphate.
AB  - We previously reported that adenosine 5'-triphosphate (ATP) inhibited the growth
      of various bacteria, including mycobacteria, Staphylococcus, and Pseudomonas,
      without damaging bacterial surface structures. Notably, ATP's antibacterial
      activity was found to be attributable to its iron-chelating ability. ATP
      exhibited combined effects with some antimicrobials against Mycobacterium
      intracellulare and methicillin-resistant S. aureus, suggesting its usefulness as
      an adjunctive drug in the chemotherapy against certain intractable infections. In
      this study, we examined detailed profiles of the anti-Mycobacterium avium complex
      (MAC) activity of some antimicrobial agents, including clarithromycin (CLA),
      rifampin (RIF), rifabutin (RBT), and ethambutol (EMB), in combination with ATP.
      It was found that the anti-MAC activity of CLA+RIF, CLA+RBT, and CLA+EMB was
      markedly potentiated in a strain-dependent manner. In this case, the onset of the
      regrowth of antimicrobial agent-treated mycobacteria during cultivation was
      significantly delayed in the presence of ATP, indicating the usefulness of ATP as
      an adjunctive drug in chemotherapy against MAC infections.

PMID- 28511781
TI  - Correlation of right atrial enlargement on ECG to right atrial volume by
      echocardiography in patients with pulmonary hypertension.
AB  - Previous attempts to validate ECG criteria for right atrial (RA) enlargement
      (RAE) have been limited by sample sizes and lack of accepted standards for
      measuring RA size. New guidelines have recommended that RA volume (RAV) be used
      to determine RA size. Since these guidelines were released, no studies have been
      published that correlate RAE by ECG to RAV using the new standards. We aimed to
      validate previously proposed ECG criteria for RAE, commonly called P pulmonale,
      and to establish whether a correlation exists between P wave amplitudes and RAV
      as determined by echocardiogram in patients from the pulmonary hypertension (PHT)
      clinic. We identified patients from the PHT clinic that had an echocardiogram and
      ECG done at most 30days apart. We defined increased P wave amplitude as >=2mm in
      lead II and >=1mm in lead V1. The RA was determined to be enlarged if the RAV
      index (RAVI) was >=39mL/m2 for men and >=33mL/m2 for women. Patients were
      stratified into four groups: those with P II>=2mm, those with P V1>=1mm, those
      that met both criteria, and those that met neither. Right atrial volumes were
      then compared. Sixty-three patients were included in the study (7 men, 56 women).
      Three men and 36 women had an ECG that met criteria for P pulmonale. Five men and
      28 women had an enlarged RA on echocardiogram. Sixty-nine percent of ECGs that
      met criteria for RAE were associated with increased RAV by echocardiogram. The
      specificity of each of the ECG criteria for P pulmonale at detecting RAE was 100%
      for men. The criterion with the highest specificity among women was P II>=2mm AND
      P V1>=1mm (94%). The least specific criterion for women was P II>=2mm (70%). The
      sensitivity of each criterion was much lower. The most sensitive criteria for men
      and women were P V1>=1mm (66.6%) and P II>=2mm (48%), respectively. The
      correlation of P wave amplitude in leads II and V1 and RAVI was not statistically
      significant for any of the ECG criteria for P pulmonale. In patients from the PHT
      clinic, the specificity of P pulmonale for detecting RAE is high, but the
      sensitivity is relatively low. These results suggest that in PHT, P pulmonale can
      be used to confirm that the RA is enlarged, but it is not a reliable test for
      diagnosing RAE.

PMID- 28511782
TI  - Prevalence of early repolarization pattern in patients with lone atrial
      fibrillation.
AB  - BACKGROUND: The objective of this study was to test the association of early
      repolarization pattern (ER) with lone atrial fibrillation (AF). METHODS:
      Electrocardiograms (ECGs) were analyzed in blinded fashion in a case-control
      study of 182 patients with lone AF and 182 controls without AF. RESULTS: Patients
      with lone AF and controls had similar frequencies of ER pattern (15% vs. 19%,
      p=0.40). In patients <50years of age, there was also no difference in the
      percentage of patients with ER in the AF and control groups (17% vs. 19%,
      p=0.60). ER pattern was more common in patients with ECG voltage criteria of left
      ventricular hypertrophy (LVH), with ER present in 57% of patients with elevated
      Sokolow-Lyon voltage compared to 14% of those without (p<0.0001). CONCLUSIONS: No
      association could be identified between the ER pattern and lone AF in young and
      middle-aged patients. In this age group, ER is substantially more common in
      patients with elevated Sokolow-Lyon voltage criteria.

PMID- 28511784
TI  - Editor in Chief's response: Women's talents.

PMID- 28511783
TI  - Is elaboration of affective content sufficient to attenuate emotional responses
      during reappraisal procedures?
AB  - Reappraisal is an emotion regulation strategy which involves changing the
      interpretation of emotional stimuli. It decreases measures of negative affect
      together with markers of emotional processing, including late positive potential
      (LPP). Affective responses can also be attenuated by various cognitive tasks. As
      reappraisal tasks require cognitive effort to elaborate emotional stimuli, it is
      possible that the observed reduction of the LPP amplitude during reinterpretation
      is, at least partly, caused by an unspecific cognitive activity. The aim of the
      study was to examine, whether mental activity other than cognitive change carried
      out directly on affective stimuli can be a factor that significantly modifies the
      intensity of the emotional responses. Three groups took part in an experiment
      with standardized emotional pictures: a reappraisal group (trained in
      reinterpretation), a retro group (trained in cognitive elaboration of emotional
      stimuli other than cognitive change), and a control group (passive viewing). The
      early LPP potential showed a main effect of group with the highest amplitude in
      the control group and the lowest amplitude in the reappraisal group. The retro
      group revealed no significant differences comparing with the other two groups.
      The late LPP was indistinguishable in the reappraisal and retro groups, which
      showed an equal decrease in its amplitude compared to the control group in the
      case of negative stimuli. Conversely, behavioral ratings collected in a separate
      group of subjects showed a decrease in negative feelings in the reappraisal group
      only. We conclude that the LPP component during reappraisal is under additive
      influence from the cognitive change itself and from unspecific cognitive
      activity; however, both of them differ in regard to their temporal
      characteristics.

PMID- 28511785
TI  - Reply to "Letter to the Editor" by Moran et al. "Comment on 'Potentized estrogen
      in homeopathic treatment of endometriosis associated pelvic pain: A 24-week,
      randomized, double-blind, placebo-controlled study'".

PMID- 28511786
TI  - Corrigendum to "The neuroprotective compound P7C3-A20 promotes neurogenesis and
      improves cognitive function after stroke" [Exp. Neurol. 290 (2017) 63-73].

PMID- 28511788
TI  - Porous structure of ion exchange membranes investigated by various techniques.
AB  - A comparative review of various techniques is provided: mercury intrusion
      porosimetry, nitrogen sorption porosimetry, differential scanning calorimetry
      (DSC)-based thermoporosimetry, and standard contact porosimetry (SCP), which
      allows determining pore volume distribution versus pore radius/water binding
      energy in ion-exchange membranes (IEMs). IEMs in the swollen state have a labile
      structure involving micro-, meso- and macropores, whose size is a function of the
      external water vapor pressure. For such materials, the most appropriate methods
      for quantifying their porosity are DSC and SCP. Especially significant
      information is given by the SCP method allowing measuring porosimetric curves in
      a very large pore size range from 1 to 105nm. Experimental results of water
      distribution in homogeneous and heterogeneous commercial and modified IEMs are
      presented. The effect of various factors on water distribution is reviewed, i.e.
      nature of polymeric matrix and functional groups, method for membrane
      preparation, membrane ageing. A special attention is given to the effect of
      membrane modification by embedding nanoparticles in their structure. The
      porosimetric curves are considered along with the results of electrochemical
      characterization involving the measurements of membrane conductivity, as well as
      diffusion and electroosmotic permeability. It is shown that addition of
      nanoparticles may lead to either increase or decrease of water content in IEMs,
      different ranges of pore size being affected. Hybrid membranes modified with
      hydrated zirconium dioxide exhibit much higher permselectivity in comparison with
      the pristine membranes. The diversity of the responses of membrane properties to
      their modification allows for formation of membranes suitable for fuel cells,
      electrodialysis or other applications.

PMID- 28511787
TI  - Comparative and cost-effectiveness research: Competencies, opportunities, and
      training for nurse scientists.
AB  - BACKGROUND: Comparative and cost-effectiveness research develops knowledge on the
      everyday effectiveness and value of treatments and care delivery models. PURPOSE:
      To describe comparative and cost-effectiveness research; identify needed
      competencies for this research; identify federal funding; and describe current
      training opportunities. METHODS: Published recommended competencies were
      reviewed. Current federal funding and training opportunities were identified. A
      federally funded training program and other training opportunities are described.
      DISCUSSION: Fourteen core competencies were identified that have both analytic
      and theoretical foci from nursing and other fields. There are multiple sources of
      federal funding for research and training. Interdisciplinary training is needed.
      CONCLUSION: Comparative and cost-effectiveness research has the opportunity to
      transform health care delivery and improve the outcomes of patients. Nurses, as
      clinicians and scientists, are in a unique position to contribute to this
      important research. We encourage nurses to seek the needed interdisciplinary
      research training to participate in this important endeavor. We also encourage
      educators to use the competencies and processes identified in current training
      programs to help shape their doctoral programs.

PMID- 28511789
TI  - Salicylic acid mediated growth, physiological and proteomic responses in two
      wheat varieties under drought stress.
AB  - : Salicylic acid (SA) induced drought tolerance can be a key trait for increasing
      and stabilizing wheat production. These SA induced traits were studied in two
      Triticum aestivum L. varieties; drought tolerant, Kundan and drought sensitive,
      Lok1 under two different water deficit regimes: and rehydration at vegetative and
      flowering stages. SA alleviated the negative effects of water stress on
      photosynthesis more in Kundan. SA induced defense responses against drought by
      increasing antioxidative enzymes and osmolytes (proline and total soluble
      sugars). Differential proteomics revealed major role of carbon metabolism and
      signal transduction in enhancing drought tolerance in Kundan which was shifted
      towards defense, energy production and protection in Lok1. Thioredoxins played
      important role between SA and redox signaling in activating defense responses. SA
      showed substantial impact on physiology and carbon assimilation in tolerant
      variety for better growth under drought. Lok1 exhibited SA induced drought
      tolerance through enhanced defense system and energy metabolism. Plants after
      rehydration showed complete recovery of physiological functions under SA
      treatment. SA mediated constitutive defense against water stress did not
      compromise yield. These results suggest that exogenously applied SA under drought
      stress confer growth promoting and stress priming effects on wheat plants thus
      alleviating yield limitation. BIOLOGICAL SIGNIFICANCE: Studies have shown
      morphological, physiological and biochemical aspects associated with the SA
      mediated drought tolerance in wheat while understanding of molecular mechanism is
      limited. Herein, proteomics approach has identified significantly changed
      proteins and their potential relevance to SA mediated drought stress responses in
      drought tolerant and sensitive wheat varieties. SA regulates wide range of
      processes such as photosynthesis, carbon assimilation, protein metabolism, amino
      acid and energy metabolism, redox homeostasis and signal transduction under
      drought. Proteome response to SA during vegetative and reproductive growth gave
      an insight on mechanism related water stress acclimation for growth and
      development to attain potential yield under drought. The knowledge gained can be
      potentially applied to provide fundamental basis for new strategies aiming
      towards improved crop drought tolerance and productivity.

PMID- 28511790
TI  - The use of front-back arrays by young children to code locations.
AB  - Research suggests that during the first 2years of life, children use an
      egocentric reference system and an extrinsic reference frame, the latter being
      one allocentric reference system, to encode locations. However, little is known
      about children's use of an object's intrinsic structure, another allocentric
      reference system. The current study focused on the role of the front-back
      relationship, one of the simplest intrinsic reference frames, in children's
      location encoding. Children (3- to 5-year-olds) participated in a hide-and-find
      game with one of three different intrinsic front-back array conditions: a facet
      induced front-back array, a motion-induced front-back array, or no array. The
      results showed that whereas the ability to use a facet-induced front-back array
      began by 3years of age, children used a motion-induced front-back array to encode
      locations at 4years of age. These results provide evidence that the developmental
      trajectories of using an intrinsic reference frame to encode locations vary and
      depend on the specific spatial array involved.

PMID- 28511791
TI  - [Usefulness of the budget and the balanced scorecard in managing Primary Care
      Centres. Impact on staff motivation].
AB  - OBJECTIVE: To analyse the utility perceived by managers of centers of primary
      care about management tools (budget and balanced scorecard), together their
      impact on human resources motivation. DESIGN: Qualitative study (case study)
      based on grounded theory performed between January and June 2014. LOCATION: Units
      of Clinical Management of Primary Health (UGCAP) in Metropolitan Health Area of
      Seville, Spain. PARTICIPANTS: UGCAP managers and Health Area (CEO) managers.
      METHOD: Data were collected through 8 semi-structured interviews using non
      probabilistic intentional sampling with representation and sufficiency criteria
      of discourse. Interviews were recorded, literally transcripted and analysis
      through in-vivo codes. RESULTS: Both tools are fully implemented but differently
      used in primary care centers. Budget is perceived as a coercive management tool,
      which has been imposed for cost saving; however, it is scarcely adequate for day
      by-day management. While balanced scorecard is a more flexible tool that allows
      identifying financial and welfare problems, budgeting limits heavily reduce the
      possibility of implementing adequate solutions. The policy of incentives is not
      adequate either, leading on de-motivation. CONCLUSIONS: This study shows that
      budgeting restrictions have led to a significant reduction in autonomy of Spanish
      Primary Care centers. Management decision making is much centralised, also
      focused on cost saving over quality of healthcare. As a result, two needs emerge
      for the future: increasing centers' autonomy and improving staff commitment
      through training and professional development programs.

PMID- 28511792
TI  - Mechanisms of hemispheric lateralization: A replication study.
AB  - It has been shown, using functional magnetic resonance imaging (fMRI), that
      hemispheric lateralization of brain activity depends on the requirements of the
      cognitive task performed during the processing of a sensory stimulus rather than
      on the intrinsic characteristics of that stimulus [Stephan et al., 2003, Science
      301 (5631): 384-6]. Task-dependent increase in the coupling of the anterior
      cingulate cortex (ACC), a region involved in cognitive control, and brain areas
      in the left prefrontal and right parietal cortex, respectively, regions involved
      in task execution, was proposed as the mechanism underlying this task-dependency
      of hemispheric lateralization. The aim of the present study was two-fold: First,
      we aimed for a conceptual replication of these findings in an independent sample
      of subjects. Second, we investigated the test-retest reliability of the imaging
      paradigm to assess whether the task can be used to capture reliable measures of
      inter-individual differences in hemispheric lateralization. We were able to
      confirm previous findings showing that hemispheric lateralization depends on the
      nature of the cognitive task rather than on the nature of the processed stimuli.
      The task-related brain activation patterns were highly reliable across sessions
      (as indicated by intra-class correlation coefficients - ICCs, >=.51). We could,
      however, not replicate previous results proposing task-dependent changes in the
      coupling between ACC and brain regions for task execution as the mechanism
      underlying hemispheric lateralization. This re-opens the question which
      mechanisms could determine the task-dependent functional asymmetries that were
      observed previously and replicated in this study.

PMID- 28511793
TI  - Two sources of dopamine for the hippocampus.
AB  - Dopaminergic signalling is established as playing an important role in novelty
      related modulation of hippocampal memory. Two recent studies have identified the
      noradrenergic fibres originating in the locus coeruleus as an additional source
      of neurotransmitter acting on dopaminergic receptors in the hippocampus.

PMID- 28511794
TI  - Application of end-tidal carbon dioxide monitoring via distal gas samples in
      ventilated neonates.
AB  - BACKGROUND: Previous research has suggested correlations between the end-tidal
      partial pressure of carbon dioxide (PETCO2) and the partial pressure of arterial
      carbon dioxide (PaCO2) in mechanically ventilated patients, but both the
      relationship between PETCO2 and PaCO2 and whether PETCO2 accurately reflects
      PaCO2 in neonates and infants are still controversial. This study evaluated
      remote sampling of PETCO2 via an epidural catheter within an endotracheal tube to
      determine the procedure's clinical safety and efficacy in the perioperative
      management of neonates. METHODS: Abdominal surgery was performed under general
      anesthesia in 86 full-term newborns (age 1-30 days, weight 2.55-4.0 kg, American
      Society of Anesthesiologists class I or II). The infants were divided into 2
      groups (n = 43 each), and carbon dioxide (CO2) gas samples were collected either
      from the conventional position (the proximal end) or a modified position (the
      distal end) of the epidural catheter. RESULTS: The PETCO2 measured with the new
      method was significantly higher than that measured with the traditional method,
      and the difference between PETCO2 and PaCO2 was also reduced. The accuracy of
      PETCO2 measured increased from 78.7% to 91.5% when the modified sampling method
      was used. The moderate correlation between PETCO2 and PaCO2 by traditional
      measurement was 0.596, which significantly increased to 0.960 in the modified
      sampling group. Thus, the PETCO2 value was closer to that of PaCO2. CONCLUSION:
      PETCO2 detected via modified carbon dioxide monitoring had a better accuracy and
      correlation with PaCO2 in neonates.

PMID- 28511795
TI  - miR-142-5p regulates tumor cell PD-L1 expression and enhances anti-tumor
      immunity.
AB  - Cancer immunotherapy has many great achievements in recent years. One of the most
      promising cancer immunotherapies is PD-1/PD-L1 pathway blockade. miRNAs
      (MicroRNAs) belongs to small noncoding RNA and can regulate gene expression by
      binding to the 3'UTR. Many miRNAs can inhibit cancer growth by regulating the PD
      L1 expression in cancer cells. Herein, we firstly found that PD-L1 could be the
      target of miR-142-5p by using bioinformatics methods, then we conduct luciferase
      activity assay, RT-PCR and western blot experiments to demonstrate that miR-142
      5p can regulate PD-L1 expression by binding to its 3'UTR. And in vivo experiments
      certified that miR-142-5p overexpression can inhibit pancreatic cancer growth.
      Flow cytometry and RT-PCR experiment demonstrated that miR-142-5p overexpression
      on tumor cells inhibits the expression of PD-L1 on tumor cells which result in
      the increase of CD4+ T lymphocytes and CD8+ T lymphocytes, the decrease of PD-1+
      T lymphocytes and increase of IFN-gamma and TNF-alpha. So, miR-142-5p
      overexpression can enhance anti-tumor immunity by blocking PD-L1/PD-1 pathway.
      Our results identify a novel mechanism by which PD-L1 is regulated by miR-142-5p
      and overexpression of miR-142-5p could enhance the anti-tumor immunity.

PMID- 28511796
TI  - Attenuation of deregulated miR-369-3p expression sensitizes non-small cell lung
      cancer cells to cisplatin via modulation of the nucleotide sugar transporter
      SLC35F5.
AB  - Deregulation of the microRNAs (miRNAs), a cluster of important
      posttranscriptional regulators, has been frequently associated with lung cancer
      (LCa). However, the emerging mechanism for how miRNAs is linked causally in the
      development of LCa chemoresistance is poorly understood. Herein, we established
      for the time the up-regulation of miR-369-3p in cisplatin (DDP)-resistant
      nonsmall cell lung cancer (NSCLC) tissues and cells. Its deregulation was found
      to be correlated to the magnitude of malignancy in well-characterized LCa cells.
      Functionally, inhibition of miR-369-3p sensitized LCa cells to DDP and suppressed
      the invasive capability in the presence of DDP treatment, whereas miR-369-3p
      overexpression promoted DDP resistance and thereby enhanced LCa cells
      invasiveness. Mechanistically, bioinformatics coupled with luciferase and gain-of
      function, loss-of-function assays revealed that miR-369-3p may regulate DDP
      chemoresistance by directly targeting the 3' untranslated region (UTR) of human
      solute carrier 35F5 (SLC35F5), as application of miR-369-3p inhibitors or
      reintroduction of epigenetically silenced SLC35F5 both individually sensitized
      LCa cells to DDP, but combined treatment with miR-369-3p inhibitors and SLC35F5
      overexpression failed to sensitized LCa cells further to DDP-elicited cell death.
      Our results provide evidence that the oncomiR effect of miR-369-3p may be
      mediated through disrupting the nucleotide sugar transportation and that SLC35F5
      is a key effector of this chemoresistance-promoting activity.

PMID- 28511797
TI  - Deficiency of liver-X-receptor-alpha reduces glucose uptake and worsens post
      myocardial infarction remodeling.
AB  - Liver X receptor alpha (LXRalpha) is an endogenous protective receptor against
      ischemic heart diseases. However, whether LXRalpha regulated glucose metabolism
      in ischemic heart diseases has not been investigated. In this study we
      investigated the involvement of LXRalpha on glucose metabolism in cardiac
      remodeling after myocardial infarction (MI). MI was induced in mice by permanent
      ligation of the left anterior descending coronary artery (LCA). Genetic LXRalpha
      deletion significantly worsened cardiac remodeling and impaired cardiac function
      at 4 weeks after MI. Cardiac 18F-fluorodeoxyglucose (FDG) uptake by positron
      emission tomography (PET) demonstrated that the FDG standardized uptake value
      (SUV) was significantly lower in LXRalpha-/- mice as compared to WT mice.
      Mechanistically, GLUT1/4 and AMPK phosphorylation were significantly
      downregulated while CD36 expression was markedly upregulated in LXRalpha-/- mice.
      This study demonstrated that deficiency of LXRalpha decreased glucose uptake
      after MI, resulting in a metabolic shift that suppressed glucose metabolism,
      which was in association with adverse cardiac remodeling.

PMID- 28511798
TI  - Induction of copper and iron in acute cold-stimulated brown adipose tissues.
AB  - Copper (Cu) and iron (Fe), the enzymatic cofactors required for various
      biochemical processes, have been recently linked to lipid metabolism. Adipose
      tissues play central roles in energy balance and whether copper and iron
      homeostasis is involved in cold-stimulated energy metabolism remains unknown. In
      this study, the Cu and Fe contents in interscapular brown adipose tissue (BAT)
      and subcutaneous white adipose tissue (subWAT) from mice at different
      developmental stages were measured. Our results revealed the dynamic changes of
      Cu and Fe levels during development, suggesting their potential roles in energy
      homeostasis. Furthermore, the significantly increased Cu and Fe contents and the
      markedly up-regulated CTR1 and ATP7A expression in acute cold-stimulated BAT
      indicates the involvement of both Cu and Fe in the BAT-mediated thermogenesis.
      Comparably, no change in the Cu and Fe levels in cold-stimulated subWAT was
      observed at the indicated time points, suggesting that both metals are not
      involved in the cellular process of cold-induced WAT browning. Taken together,
      these data demonstrate the induction of Cu and Fe in acute cold-stimulated BAT
      activation, thus providing the direct evidences of the involvement of copper and
      iron homeostasis in BAT-mediated non-shivering energy metabolism.

PMID- 28511799
TI  - Towards a Grand Unified Theory of sports performance: A response to the
      commentaries.

PMID- 28511800
TI  - Epidemiologic pattern of paediatric supracondylar fractures of humerus in a
      teaching hospital of rural India: A prospective study of 263 cases.
AB  - PURPOSE: This prospective study aimed to investigate the epidemiologic parameters
      of supracondylar humeral fractures in children admitted to a teaching institution
      of a developing country primarily catering to rural population, to find any
      preventable cause of such injuries. METHODS: All suspected cases of supracondylar
      humeral fracture reporting to emergency or outpatients department were analysed
      for various epidemiologic parameters including age, sex, laterality, time of
      presentation, associated injuries, neurovascular complications and classification
      over a period of four years. RESULTS: We analysed a total of 263 patients and
      most of the fractures were seen in 5-8-year age group with a mean of 7.9 years. A
      total of 157 cases were males and non-dominant extremity was involved in 65% of
      fractures in our series. Fall on outstretched hand was the predominant cause of
      injury and fall from rooftop was the predominant mode. In all patients, 36.12%
      reported to our hospital 1 week after injury, 39.92% presented to hospital within
      48 h after trauma and the remaining 23.95% presented 48 h to 1 week after trauma.
      None had a bilateral injury. Gartland type 3 fractures constituted 54.37% of
      patients, followed by type 1 (23.95%) and type 2 (21.67%). CONCLUSION: Almost one
      fourth of supracondylar humeral fractures in children can be prevented by
      installing railing of rooftops and stairs. It is necessary to educate people on
      hazards of treatment by traditional bonesetters. Moreover, the children with
      supracondylar humeral fractures should be screened for associated injuries.

PMID- 28511801
TI  - Intergenerational differences in the effects of transcatheter closure of atrial
      septal defects on cardiac function.
AB  - BACKGROUND: Little is known regarding intergenerational differences in the
      effects of atrial sepal defect (ASD) closure on the left heart. We therefore
      analyzed age-related serial changes in the left heart following ASD closure.
      METHODS: We studied 50 patients with an isolated ASD who underwent successful
      transcatheter closure using Amplatzer septal occluders (St. Jude Medical, Little
      Canada, MN, USA) between June 2007 and June 2013. Patients were divided into
      three age groups: young patients aged <=17 years; middle-aged patients aged 18-50
      years; and older patients aged >50 years. Multi-modal echocardiographic studies
      with different views were performed before and at 1 day, 1-3 months, and 6-12
      months after ASD closure. Echocardiographic variables were compared among the
      groups at different time points after closure. RESULTS: Left ventricular end
      diastolic and end-systolic volume indices (EDVI and ESVI) in the older group were
      significantly smaller than those in the other groups before closure. EDVI and
      ESVI increased with time after closure in all groups with stable ejection
      fractions. However, EDVI and ESVI remained significantly smaller in the older
      group compared with the other groups. There was a significant interaction among
      the age groups only in terms of left atrial volume index (LAVI). LAVI increased
      significantly with time in the older group, but did not change in the other
      groups. CONCLUSION: Although the left ventricle enlarged with time after ASD
      closure in all age groups, left ventricular size in older patients never reached
      that in younger patients. In addition to this inadequate enlargement of the left
      ventricle, diastolic dysfunction might also result in late left atrial
      enlargement in older patients following ASD closure.

PMID- 28511802
TI  - [A continuous series of 27 adult patients treated for L5-S1 isthmic
      spondylolisthesis by combined approach: Clinical and radiological outcomes at 1
      year follow-up].
AB  - Through this single-center consecutive prospective study, we evaluated the
      results of a combined approach for L5-S1 isthmic spondylolisthesis, using a
      polyetheretherketone (PEEK) interbody lordotic cage during anterior approach and
      pedicle screw-based posterior fixation. Between 2010 and 2014, 27 adult patients
      were treated for L5-S1 isthmic spondylolisthesis (high and low grades) by a
      combined approach with a minimum follow-up of one year. Clinical outcome was
      assessed before surgical treatment and at four months and one year after surgery
      by: VAS, Oswestry Index (ODI) and Rolland-Morris scores. Two observers evaluated
      the following radiological parameters: pelvic incidence, pelvic tilt, lumbar
      lordosis, segmental lordosis L5-S1, anterior and posterior disc height, spinal
      vertical axis (SVA), SVA/sacro-femoral distance (SFD) ratio. Fusion was evaluated
      on the CT scan at one-year follow-up. Blood loss, surgery time and complications
      were also collected. The mean age was 47.7 years (+/-16.9). The VAS, ODI and
      Rolland-Morris scores were significantly improved postoperatively, decreased from
      7.5 (+/-1.45); 48 (+/-19.25); 15.3 (+/-4.67) before the surgery to 3.8 (+/-2.55);
      28.7 (+/-19.58) and 7.76 (+/-7.21) respectively at one year after the surgery
      (P=0.05). The mean follow-up was 3.3 years. Mean surgery time was 193.7min (+/
      37). Fusion was obtained in 100% of cases. Segmental lordosis L5-S1, pelvic tilt,
      slippage, anterior and posterior L5-S1 disc height were significantly improved
      postoperatively, they passed from 20.1; 22.6; 35.3%; 26.4%; 17.9% to 29.5; 20.6;
      20.3%; 64.4%; 36.3% respectively. Combined surgical procedure meets the required
      goals of surgery in the treatment of adults L5-S1 isthmic spondylolisthesis.

PMID- 28511803
TI  - Group members' questions shape participation in health counselling and health
      education.
AB  - OBJECTIVE: This study examines how group members' questions shape member
      participation in health counselling and health education groups. METHODS: The
      study applies conversation analytic principles as a method. The data consist of
      video-recorded health education lessons in secondary school and health
      counselling sessions for adults with a high risk of Type 2 diabetes. RESULTS:
      Group members' questions accomplish a temporary change in participatory roles.
      They are used to 1) request counselling, 2) do counselling or 3) challenge
      previous talk. They are usually treated as relevant and legitimate actions by the
      participants, but are occasionally interpreted as transitions outside the current
      action or topic. CONCLUSION: Group members' questions result in a shift from
      leader-driven to member-driven discussion. Thus they constitute a pivot point for
      detecting changes in participation in group interventions. PRACTICE IMPLICATIONS:
      Observing the occurrence of group members' questions helps group leaders to
      adjust their own actions accordingly and thus facilitate or guide group
      participation. Comparison of the type and frequency of members' questions is a
      way to detect different trajectories for delivering group interventions and can
      thus be used to develop methods for process evaluation of interventions.

PMID- 28511805
TI  - Evidence for resection of sarcoma pulmonary metastases: More, but better?

PMID- 28511804
TI  - How long do I have? Observational study on communication about life expectancy
      with advanced cancer patients.
AB  - OBJECTIVE: To examine how communication about life expectancy is initiated in
      consultations about palliative chemotherapy, and what prognostic information is
      presented. METHODS: Patients with advanced cancer (n=41) with a median life
      expectancy <1year and oncologists (n=6) and oncologists-in-training (n=7) meeting
      with them in consultations (n=62) to discuss palliative chemotherapy were
      included. Verbatim transcripts of audio-recorded consultations were analyzed
      using MAXqda10. RESULTS: Life expectancy was addressed in 19 of 62 of the
      consultations. In all cases, patients took the initiative, most often through
      direct questions. Estimates were provided in 12 consultations in various formats:
      the likelihood of experiencing a significant event, point estimates or general
      time scales of "months to years", often with an emphasis on the "years". The
      indeterminacy of estimates was consistently stressed. Also their potential
      inadequacy was regularly addressed, often by describing beneficial prognostic
      predictors for the specific patient. Oncologists did not address the reliability
      or precision of estimates. CONCLUSION: Oncologists did not initiate talk about
      life expectancy, they used different formats, emphasized the positive and
      stressed unpredictability, yet not ambiguity of estimates. PRACTICE IMPLICATIONS:
      Prognostic communication should be part of the medical curriculum. Further
      research should address the effect of different formats of information provision.

PMID- 28511806
TI  - STEMI could be the primary presentation of acute aortic dissection.
AB  - BACKGROUND: Stanford type A aortic dissection (TAAD) may lead to coronary artery
      occlusion and malfunction. However, TAAD manifesting as acute ST-segment
      elevation myocardial infarction (STEMI) has not been studied. In the present
      study, we reported 8 TAAD cases with STEMI as the primary presentation, and
      analyzed their clinical characteristics and outcome. METHODS: The records were
      reviewed for patients admitted to the large comprehensive university hospital for
      PCI due to STEMI from January 1, 2002 to January 1, 2017. RESULTS: The incidence
      of STEMI secondary to TAAD in our center was 0.51% (8/1,576). A total of 5
      patients underwent urgent coronary angiography (CAG) without awareness of TAAD.
      Compression at the ostium of right coronary artery (RCA) was found in 2 patients,
      dissected flap of RCA in 1 patient, and heterogeneous filling and false lumen in
      RCA in 1 patient. Three of these 5 patients received surgery and survived. One
      patient accepted urgent RCA stenting because of cardiogenic shock and died after
      refusal of surgical therapy and failure of medical treatment. Another 2 patients
      received thrombolytic therapy died prior to CAG. Thus, the total in-hospital
      mortality was 37.5% (3/8). CONCLUSIONS: TAAD presenting as STEMI was a rare
      condition that predominantly involved RCA. A quick and correct clinical diagnosis
      of STEMI caused by TAAD prior to invasive procedure would be important. Urgent
      CAG without awareness of TAAD could provide important information for a timely
      diagnosis. High level of suspicion and awareness is the key to establishing the
      diagnosis and achieving optimal clinical outcome.

PMID- 28511807
TI  - Does the novel lateral trauma position cause more motion in an unstable cervical
      spine injury than the logroll maneuver?
AB  - OBJECTIVE: Prehospital personnel who lack advanced airway management training
      must rely on basic techniques when transporting unconscious trauma patients. The
      supine position is associated with a loss of airway patency when compared to
      lateral recumbent positions. Thus, an inherent conflict exists between securing
      an open airway using the recovery position and maintaining spinal immobilization
      in the supine position. The lateral trauma position is a novel technique that
      aims to combine airway management with spinal precautions. The objective of this
      study was to compare the spinal motion allowed by the novel lateral trauma
      position and the well-established log-roll maneuver. METHODS: Using a full-body
      cadaver model with an induced globally unstable cervical spine (C5-C6) lesion, we
      investigated the mean range of motion (ROM) produced at the site of the injury in
      six dimensions by performing the two maneuvers using an electromagnetic tracking
      device. RESULTS: Compared to the log-roll maneuver, the lateral trauma position
      caused similar mean ROM in five of the six dimensions. Only medial/lateral linear
      motion was significantly greater in the lateral trauma position (1.4mm (95%
      confidence interval [CI] 0.4, 2.4mm)). CONCLUSIONS: In this cadaver study, the
      novel lateral trauma position and the well-established log-roll maneuver resulted
      in comparable amounts of motion in an unstable cervical spine injury model. We
      suggest that the lateral trauma position may be considered for unconscious non
      intubated trauma patients.

PMID- 28511810
TI  - The Case for an Epilepsy and Clinical Neurophysiology Match.

PMID- 28511808
TI  - Astaxanthin from shrimp efficiently modulates oxidative stress and allied cell
      death progression in MCF-7 cells treated synergistically with beta-carotene and
      lutein from greens.
AB  - This study investigated the synergistic efficacy of keto-carotenoid astaxanthin
      (AST, from shrimp) plus hydrocarbon (beta-carotene, BC) and hydroxyl (lutein, L)
      carotenoids (from greens) on molecular events in MCF-7 cells. MCF-7 cells were
      treated with either of carotenoid (20 MUM, AST or BC or L) separately or the
      mixture of them (an equimolar concentration of carotenoids mixture, CM) or
      saponified carotenoid extract from shrimp (SSCE) for 48 h and analyzed cellular
      uptake, cytotoxicity, and apoptosis. The IC50 and combination-index values of AST
      co-treatment with a lower concentration of BC and L (5 MUM) exhibited enhanced
      cytotoxicity and oxidative stress as compared with individual carotenoids or
      SSCE. Further, higher cellular uptake/accumulation of AST along with BC and L
      found to synergistically induce apoptosis through modulation of cyclin D1, p53,
      Bax and Bcl-2 expressions by arresting cell cycle at G0/G1 phase. Further, CM or
      SSCE treatments are unlikely to affect proliferation of normal breast epithelial
      cells (MCF-10A). The results of selective killing of MCF-7 cells demonstrated a
      greater insight on the synergistic effect of shrimp AST plus BC and L. It is
      concluded that consumption of shrimp along with green leafy vegetables helps in
      combating cancer chemoprevention.

PMID- 28511811
TI  - Autoimmune Voltage-Gated Potassium Channelopathy Presenting With Catecholamine
      Excess.
AB  - BACKGROUND: Autoimmune voltage-gated potassium channelopathies have been
      associated with a range of neurological presenting symptoms, including central,
      peripheral, and autonomic dysfunction. PATIENT DESCRIPTION: We describe a 12-year
      old boy who presented with nine months of pain, anxiety, and 30-pound weight
      loss. He was admitted for failure to thrive, then noted to be persistently
      hypertensive and tachycardic. Plasma metanephrines and urine metanephrines and
      catecholamines were elevated. Extensive investigation for causes of elevated
      catecholamines, such as hyperthyroidism or catecholamine-secreting tumor, was
      negative. A paraneoplastic panel was positive for voltage-gated potassium channel
      antibodies. Treatment with intravenous immunoglobulin and pulse
      methylprednisolone led to complete resolution of symptoms, weight gain, and
      normalization of vital signs and plasma metanephrines. CONCLUSION: Voltage-gated
      potassium channel antibodies should be considered as part of the differential in
      patients presenting with elevated metanephrine and catecholamine secretion.

PMID- 28511809
TI  - Characterisation of the selective binding of antibiotics vancomycin and
      teicoplanin by the VanS receptor regulating type A vancomycin resistance in the
      enterococci.
AB  - A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the
      leading hospital acquired infectious agent, the enterococci, is the most common
      in the UK. Resistance is regulated by the VanRASA two-component system,
      comprising the histidine sensor kinase VanSA and the partner response regulator
      VanRA. The nature of the activating ligand for VanSA has not been identified,
      therefore this work sought to identify and characterise ligand(s) for VanSA. In
      vitro approaches were used to screen the structural and activity effects of a
      range of potential ligands with purified VanSA protein. Of the screened ligands
      (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan
      components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala)
      only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanSA
      with different affinities (vancomycin 70MUM; teicoplanin 30 and 170MUM), and were
      proposed to bind via exposed aromatic residues tryptophan and tyrosine.
      Furthermore, binding of the antibiotics induced quicker, longer-lived
      phosphorylation states for VanSA, proposing them as activators of type A
      vancomycin resistance in the enterococci.

PMID- 28511812
TI  - Acute Management of Symptomatic Subependymal Giant Cell Astrocytoma With
      Everolimus.
AB  - BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing tumors,
      which can cause obstructive hydrocephalus in patients with tuberous sclerosis
      complex (TSC). These tumors require routine surveillance with magnetic resonance
      imaging. Current consensus guidelines recommend treatment of asymptomatic SEGAs
      with an mechanistic target of rapamycin (mTOR) inhibitor because these
      medications have demonstrated efficacy and safety in multiple prospective
      clinical trials. For symptomatic SEGAs, standard therapy typically involves
      surgical resection of the tumor to relieve mass effect and resolve hydrocephalus.
      However, resection can be associated with significant perioperative morbidity and
      complications. There are anecdotal reports of using mTOR inhibitors to reduce
      tumor size in preparation for surgery, but prospective studies comparing sole
      mTOR inhibitor therapy with surgical management have not been completed. METHODS:
      Here, we present a seven-year-old boy with a large, symptomatic SEGA which was
      treated acutely with everolimus. RESULTS: Everolimus treatment resulted in rapid
      reduction in tumor size, symptomatic improvement, and decrease in cerebrospinal
      fluid protein. CONCLUSIONS: Everolimus can effectively reduce tumor size,
      decrease cerebrospinal fluid protein, and allow successful ventriculoperitoneal
      shunt placement without the need for surgical resection of a symptomatic SEGA.

PMID- 28511813
TI  - Conservative management of mallet injuries: A national survey of current practice
      in the UK.
AB  - INTRODUCTION: Mallet injuries are common and usually treated conservatively.
      Various systematic reviews have found a lack of evidence regarding the best
      management, and it is unclear whether this uncertainty is reflected in current UK
      practice. METHODS: An online survey was developed to determine the current
      practice for the conservative treatment of mallet injury among specialist hand
      clinicians in the UK, including physiotherapists, occupational therapists and
      surgeons. Clinician's views of study outcome selection were also explored to
      improve future trials. RESULTS: In total, 336 professionals completed the survey.
      Inconsistency in overall practice was observed in splint type choice, time to
      discharge to GP, and assessment of adherence. Greater consistency was observed
      for recommended duration of continuous immobilisation. Bony injuries were most
      commonly splinted for 6 weeks (n = 228, 78%) and soft tissue injuries for either
      8 weeks (n = 172, 56%) or 6 weeks (n = 119, 39%). Post-immobilisation splinting
      was frequently recommended, but duration varied between 2 and 10 weeks. The
      outcome rated as most important by all clinicians was patient satisfaction.
      DISCUSSION: There is overall variation in the current UK conservative management
      of mallet injuries, and the development of a standardised, evidence-based
      protocol is required. Clinicians' opinions may be used to develop a core set of
      outcome measures, which will improve standardisation and comparability of future
      trials.

PMID- 28511814
TI  - Evaluation of the influence of mechanical activation on physical and chemical
      properties of municipal solid waste incineration sludge.
AB  - Despite numerous studies concerning the application of by-products in the
      construction field, municipal solid waste incineration (MSWI) residues are not
      widely used as secondary building materials. In some European countries, washing
      treatment to the full bottom ash (BA) fraction (0-32 mm) is applied, isolating
      more contaminated particles, smaller than 0.063 mm. Therefore, a MWSI sludge is
      produced, having a high moisture content, and thus a limited presence of soluble
      species. In order to enhance its performance as building material, here, dry
      mechanical activation is applied on MSWI sludge. Thereafter, a reactivity
      comparison between reference BA and untreated and treated MSWI sludge is
      provided, evaluating their behaviour in the presence of cement and their
      pozzolanic activity. Moreover, the mechanical performances, as 25% substitution
      of Portland cement (PC) are assessed, based on the EN 450. Mechanical activation
      enhances MSWI sludge physically due to the improved particle morphology and
      packing. Chemically, the hydration degree of PC is enhanced by the MSWI sludge by
      ~25%. The milling treatment proved to be beneficial to the residues performances
      in the presence of PC, providing 32% higher strength than untreated sample.
      Environmentally, the compliance with the unshaped material legislation is
      successfully verified, according to the Soil Quality Decree.

PMID- 28511815
TI  - Signature of the Sleeper Cell: A Biomarker of HIV Latency Revealed.
AB  - HIV establishes a reservoir in latently infected T cells, and this reservoir has
      long hampered curative approaches. A recent study by Descours et al. identifies
      CD32a as a marker of latently infected T cells, potentially opening the way to
      the development of strategies that directly target this critical HIV reservoir.

PMID- 28511817
TI  - The Wait.

PMID- 28511819
TI  - Psychiatric dermatology revisited.

PMID- 28511820
TI  - Somatic symptom disorder in dermatology.
AB  - Somatic symptom disorder (SSD) is defined by the prominence of somatic symptoms
      associated with abnormal thoughts, feelings, and behaviors related to the
      symptoms, resulting in significant distress and impairment. Individuals with
      these disorders are more commonly encountered in primary care and other medical
      settings, including dermatology practice, than in psychiatric and other mental
      health settings. What defines the thoughts, feelings, and behaviors as abnormal
      is that they are excessive, that is, out of proportion to other patients with
      similar somatic symptoms, and that they result in significant distress and
      impairment. SSD may occur with or without the presence of a diagnosable
      dermatologic disorder. When a dermatologic disorder is present, SSD should be
      considered when the patient is worrying too much about his or her skin, spending
      too much time and energy on it, and especially if the patient complains of many
      nondermatologic symptoms in addition. The differential diagnosis includes other
      psychiatric disorders, including depression, anxiety disorders, delusions of
      parasitosis, and body dysmorphic disorder. This paper describes SSD and its
      applicability in dermatologic practice, with illustrative cases.

PMID- 28511818
TI  - "How the other half live": Lay perspectives on health inequalities in an age of
      austerity.
AB  - This paper examines how people living in two socially contrasting areas of
      Stockton on Tees, North East England experience, explain, and understand the
      stark health inequalities in their town. Participants displayed opinions that
      fluctuated between a variety of converging and contrasting explanations. Three
      years of ethnographic observation in both areas (2014-2017) generated
      explanations which initially focused closely on behavioural and individualised
      factors, whilst 118 qualitative interviews subsequently revealed more nuanced
      justifications, which prioritised more structural, material and psychosocial
      influences. Findings indicate that inequalities in healthcare, including access,
      the importance of judgemental attitudes, and perceived place stigma, would then
      be offered as explanations for the stark gap in spatial inequalities in the area.
      Notions of fatalism, linked to (a lack of) choice, control, and fear of the
      future, were common reasons given for inequalities across all participants. We
      conclude by arguing for a prioritisation of listening to, and working to
      understand, the experiences of communities experiencing the brunt of health
      inequalities; especially important at a time of austerity.

PMID- 28511821
TI  - Somatization in the dermatology patient: Some sociocultural perspectives.
AB  - Somatization in dermatology patients is a challenge to diagnose and manage.
      Somatization presents as medically unexplained dermatologic symptoms, which are
      commonly encountered in dermatology and psychiatry practices. These cutaneous
      symptoms are often intriguing and do not fit into any particular known
      dermatologic condition. Sometimes, they may evoke negative feelings in the
      practicing dermatologist. The dermatologic somatic symptoms might be one way of
      communicating psychologic distress in a culturally acceptable method. These
      somatic symptoms may be masking another psychiatric disorder such as depression.
      They could also be an adaptive response to a difficult psychosocial situation and
      means of coping in a culturally meaningful way; therefore, the underlying
      conflicts need to be understood and managed in the sociocultural context of the
      symptoms. This chapter discusses the various unexplained physical symptoms in
      dermatology patients and the need for comprehensive evaluation.

PMID- 28511822
TI  - Posttraumatic stress disorder (PTSD) and the dermatology patient.
AB  - Dermatologic symptoms can be associated with posttraumatic stress disorder (PTSD)
      in several situations: (1) as features of some core PTSD symptoms, such as
      intrusion symptoms manifesting as cutaneous sensory flashbacks, as autonomic
      arousal manifesting as night sweats and idiopathic urticaria, and as dissociation
      manifesting as numbness and dermatitis artefacta; (2) the cutaneous psychosomatic
      effects of emotional and physical neglect and sexual abuse (eg, infantile eczema,
      cutaneous self-injury, and body-focused repetitive behaviors such as
      trichotillomania and skin picking disorder) and eating disorders, which can have
      dermatologic effects; (3) the direct effect of physical or sexual abuse or
      catastrophic life events (eg, earthquakes) on the skin; and (4) as a result of
      significant alterations in hypothalamic-pituitary-adrenal and sympatho-adrenal
      medullary axes, which can affect neuroendocrine and immune functions, and can
      lead to exacerbations of stress-reactive inflammatory dermatoses such as
      psoriasis, chronic urticaria, and atopic dermatitis. Elevated levels of
      inflammatory biomarkers and impaired epidermal barrier function have been
      reported in situations involving sustained psychologic stress and sleep
      deprivation. Some PTSD patients show hypothalamic-pituitary-adrenal axis
      hyporesponsiveness and higher circulating T lymphocytes, which can exacerbate
      immune-mediated dermatologic disorders. PTSD should be considered an underlying
      factor in the chronic, recurrent, or treatment-resistant stress-reactive
      dermatoses and in patients with self-induced dermatoses.

PMID- 28511816
TI  - Mechanisms of Immune Tolerance in Leukemia and Lymphoma.
AB  - The mechanisms through which immune responses are generated against solid cancers
      are well characterized and knowledge of the immune evasion pathways exploited by
      these malignancies has grown considerably. However, for hematological cancers,
      which develop and disseminate quite differently than solid tumors, the pathways
      that regulate immune activation or tolerance are less clear. Growing evidence
      suggests that, while numerous immune escape pathways are shared between
      hematological and solid malignancies, several unique pathways are exploited by
      leukemia and lymphoma. Below we discuss immune evasion mechanisms in leukemia and
      lymphoma, highlighting key differences from solid tumors. A more complete
      characterization of the mechanisms of immune tolerance in hematological
      malignancies is critical to inform the development of future immunotherapeutic
      approaches.

PMID- 28511823
TI  - Dissociation and conversion symptoms in dermatology.
AB  - Dissociation and conversion (defined as the somatic component of dissociation)
      can play an important mediating role in the exacerbation of the stress-reactive
      dermatoses (eg, psoriasis, idiopathic urticaria, atopic dermatitis), dermatoses
      that are exacerbated by excessive scratching (eg, lichen simplex chronicus,
      prurigo nodularis) and koebnerization, and the self-induced dermatoses
      (dermatitis artefacta, acne excoriee, skin picking disorder, trichotillomania,
      onychotillomania/onychophagia). Dissociative symptoms often coexist with
      obsessive-compulsive symptoms in the more severe cases of the self-induced
      dermatoses. Dissociation can play an important role in cutaneous sensory disorder
      (eg, scalp dysesthesia syndrome, stomatodynia/glossodynia,
      vulvodynia/scrotodynia, medically unexplained anesthesia). Dissociation typically
      occurs in the context of extreme psychosocial stress and a history of severe
      abuse/neglect during early life. Dissociative patients may experience a sense of
      detachment from their body and present in a state of extreme self-neglect,
      including denial of serious skin disorders. Amnesia is one of the core symptoms
      of dissociation; therefore, patients, who self-induce their skin lesions during a
      dissociative episode often deny self-inducing their lesions; it is important to
      recognize that this is distinct from malingering, and the lesions are not
      intentionally induced. Dissociation and conversion symptoms are typically present
      in the complex dermatology patient and should be assessed using a comprehensive
      biopsychosocial approach.

PMID- 28511824
TI  - Psychiatric disorders and pruritus.
AB  - The skin and psyche are intimately related with various skin diseases caused by
      or resulting in psychiatric disturbances. Pruritus is a commonly reported symptom
      in psychiatric patients, and likewise psychiatric co-morbidities, including
      anxiety and depression, are frequently seen in chronic pruritus patients. Primary
      psychodermatologic conditions, such as somatic symptom disorder, dermatitis
      artefacta, obsessive-compulsive and related disorders (excoriation disorder and
      prurigo nodularis), delusional infestation, and substance use disorder, can all
      induce significant pruritus in patients, severely affecting their quality of
      life. Such entities can be challenging to manage, and therefore a greater
      understanding of the underlying psychopathology and evaluation of associated
      psychosocial factors is necessary. In addition to proper skin hygiene and first
      line pharmacotherapies such as selective serotonin reuptake inhibitors,
      noradrenergic and selective serotonin antidepressants, antiepileptics, and
      antipsychotics (for delusional and psychotic disorders), patients with
      psychopruritic disorders should be offered psychotherapy to maximize the
      therapeutic efficacy.

PMID- 28511826
TI  - Use of hypnosis, meditation, and biofeedback in dermatology.
AB  - Hypnosis utilizes trance to access otherwise inaccessible repressed or
      unconscious memories and features of the psyche and control of physiology not
      attainable in the ordinary conscious waking state. Medical uses of hypnosis in
      dermatology include reducing discomfort from itching or skin pain, altering
      ingrained dysfunctional habits such as scratching, promoting healing of skin
      disorders, searching for psychosomatic aspects of skin disorders and alleviating
      them, and reframing cognitive and emotional dysfunctional patterns related to
      skin disorders. Meditation uses trance to center and balance. Medical uses of
      meditation in dermatology include relaxation to promote healing of skin disorders
      and refocusing with respect to the meaning and emotional negative valance of skin
      disorders. Biofeedback in dermatology employs instrumentation with visual or
      auditory feedback to permit conscious awareness and alteration of physiologic
      phenomena such as sweating as measured by galvanic skin resistance and skin
      temperature measured by temperature detecting devices, promoting relaxation and
      healing. These methods and techniques permit access to and intervention in
      otherwise inaccessible areas that can influence skin disorders. With proper use,
      they are very safe, with minimal, if any, side effects and sometimes produce
      significant results where other methods have failed.

PMID- 28511825
TI  - Neuropsychiatric factors in sensitive skin.
AB  - Sensitive skin is a syndrome defined by the occurrence of unpleasant sensations
      (stinging, burning, pain, pruritus, and tingling sensations) in response to
      stimuli that normally should not provoke such sensations. The worldwide
      prevalence of sensitive skin is approximately 40%. Clinical, histologic,
      biochemical, and therapeutic data show that this condition is related to changes
      in epidermal nerve endings with subsequent hyperreactivity and neurogenic
      inflammation; hence, sensitive skin is not a psychosomatic disorder, although
      psychologic consequences are possible.

PMID- 28511827
TI  - Psychosomatic aspects of vitiligo.
AB  - Vitiligo is a chronic common skin disease. The asymptomatic hypopigmented
      cutaneous lesions are considered by many health care professionals as a cosmetic
      problem only; however, vitiligo can have a major psychosocial impact on patients'
      lives. We review some of the factors responsible for this impact, such as the
      general public's wrong perception of the disease, feelings and emotional
      responses from patients, how stressful events can act as triggers of the disease,
      stigmatization experiences suffered by the patients, the prevalence of
      psychiatric morbidity, the effects on relationships and sex life, how quality of
      life in adults and children is impaired, and how treatment can improve it.

PMID- 28511828
TI  - Body dysmorphic disorder in the dermatology patient.
AB  - Body dysmorphic disorder is primarily a psychiatric disorder, in which the
      patient believes that some normal or very near normal aspect of his or her
      physical appearance is distorted or ugly. Should there be a minor abnormality, it
      is grossly exaggerated in the mind of the patient, causing feelings of shame and
      embarrassment and leading daily to spending hours at the mirror, or any
      reflecting surface, as the patient tries to conceal or remove the perceived
      abnormality through the development of ritualistic behavior. Although other
      organs can be involved-for example, the shape of the nose or a portion of an ear-
      the skin, hair, and nails are most commonly involved, while the patient
      constantly seeks reassurance about appearance from friends and family. There is a
      broad spectrum of severity in body dysmorphic disorder, ranging from obsessional
      worry to frank delusion, and the psychiatric comorbidities-anxiety, depression,
      and personality disorder-are prominent parts of the picture. Unfortunately, the
      psychiatric comorbidities and the negative impact on every aspect of the
      patient's life may not be recognized by dermatologists and other non-psychiatric
      physicians, so that effective treatment is often not instituted or appropriate
      referrals made. This paper describes the incidence, possible etiologies, and
      clinical picture of body dysmorphic disorder in dermatology patients and
      discusses interpersonal approaches that may permit appropriate treatment or
      referral to take place. Specific treatments and prognosis are also discussed.

PMID- 28511829
TI  - Suicidal behaviors in the dermatology patient.
AB  - An assessment of suicidal behaviors in the dermatology patient may be necessary
      in several situations: (1) in the presence of psychiatric comorbidity (major
      depressive disorder, body dysmorphic disorder, substance use disorder,
      posttraumatic stress disorder), encountered in up to 30% of dermatology patients;
      (2) when dermatologic symptoms ("dysmorphophobia," dermatitis artefacta)
      represent psychiatric pathologic conditions; (3) when psychosocial stressors
      (bereavement, interpersonal violence) increase the risk of suicidal behavior and
      exacerbate stress-reactive dermatoses (psoriasis, acne); (4) in the presence of
      high disease burden (chronicity, increased disease severity); (5) in instances of
      significant pruritus or chronic sleep disruption; (6) in the presence of facial
      lesions or facial scarring; (7) when social exclusion or feelings of alienation
      arise secondary to the skin disorder; (8) with use of medications (retinoids,
      biologics) for which suicidal behavior has been implicated as a possible side
      effect; and (9) when treating psychiatric patients experiencing a serious
      reaction to psychotropic medications (eg, Stevens-Johnson syndrome and
      anticonvulsants). Suicide risk must be assessed within a demographic context
      because suicide rates rise rapidly in adolescents and young adults, among whom
      the prevalence of skin disorders associated with suicidal behaviors (acne,
      psoriasis, atopic dermatitis) is also high, and suicide rates are increasing
      among white men, who tend to be overrepresented in dermatology clinical trials.

PMID- 28511830
TI  - Personality disorders and the "difficult" dermatology patient: Maximizing patient
      satisfaction.
AB  - Personality disorders (PDs) are stable and enduring patterns of thought, feeling,
      and behavior that deviate from one's cultural norms and cause impairment in
      functionality. Patients with PDs are commonly encountered in the dermatologic
      setting and can be perceived by providers as "difficult." Given that PDs are
      chronic, rigid, and frustrating to deal with, it is important to be skillful in
      the approach to such patients, especially in the era of the value-based
      reimbursement system, in which patient satisfaction is crucial for reimbursement.
      This contribution discusses four PDs most commonly encountered in the dermatology
      setting: Borderline, histrionic, obsessive-compulsive, and narcissistic. Although
      the details regarding the approach to patients for each PD differ as discussed,
      once a PD is identified, there are few key management strategies that can be
      helpful in minimizing conflict and enhancing outcomes. In patients with PD, the
      presenting skin complaint is often a secondary problem, as there may be an
      underlying psychologic issue (somatization). Understanding the underlying
      psychologic aspect of the patients' dermatologic complaints and adapting
      behaviors to the patients' needs are fundamental for maximizing patient
      satisfaction.

PMID- 28511831
TI  - Obstructive sleep apnea and dermatologic disorders.
AB  - Obstructive sleep apnea (OSA) is present in at least 2% of women and 4% of men,
      and its prevalence is increasing, because a major predisposing factor for OSA is
      a high body mass index. Psoriasis has the most strongly substantiated link with
      OSA, where the relationship may be bidirectional. Dermatologic disorders may be
      comorbid with OSA due to several factors: (i) the heightened proinflammatory
      state in OSA, which can occur independent of body mass index, and may exacerbate
      inflammatory dermatoses; (ii) intermittent hypoxemia may promote
      neovascularization and tumor growth in certain cancers, such as melanoma; (iii)
      obesity, present in majority of OSA patients, can be associated with a heightened
      proinflammatory state; (iv) upper airway obstruction due to local tumors or soft
      tissue swelling due to physical urticaria or angioedema; (v) acute nasal
      congestion in the atopic patient with allergic rhinitis; (vi) dermatologic
      disorders associated with other OSA risk factors (eg, acanthosis nigricans and
      metabolic syndrome); and (vii) a high sympathetic tone (eg, in atopic dermatitis)
      and resultant sleep fragmentation contributing to upper airway instability during
      sleep. In many instances, the dermatology patient with OSA may have other medical
      and psychiatric comorbidities that are also associated with increased OSA risk.

PMID- 28511832
TI  - Impact factor: Universalism and reliability of assessment.
AB  - In 1955, Eugene Garfield (1925-1917) published a paper in Science where for the
      first time he advocated the necessity of introducing parameters to assess the
      quality of scientific journals. Underlying this necessity was an observation of a
      trend where the whole area of influence in academic publishing was dominated by a
      narrow group of large interdisciplinary research journals. For this reason, along
      with Irving H. Sher, they created the impact factor (IF), also called the
      Garfield impact factor, journal citation rate, journal influence, and journal
      impact factor. The concept of IF concerns a research discipline called
      bibliometrics, which uses mathematical and statistical methods to analyze
      scientific publications. Established by Garfield in 1963, the Science Citation
      Index, a record of scientific publications and citations therein, contributed
      directly to the increased importance of this method. Since the 1960s, the
      register of scientific publications has expanded and their evaluation by the IF
      has become a fundamental and universal measure of the journal's value. Contrary
      to the authors' intentions in the creation of the index (IF), it is often used to
      assess the quality of contributions, simultaneously assessing the authors'
      achievements or academic career and academic institutions' funding possibilities.

PMID- 28511833
TI  - Isotretinoin in retrospect.

PMID- 28511834
TI  - An assault to the National Academies of Venezuela.

PMID- 28511836
TI  - Corrigendum to "Morbidity and mortality of very low birth weight infants in
      Taiwan-Changes in 15 years: A population based study" [J Formos Med Assoc 115
      (2016) 1039-1045].

PMID- 28511835
TI  - ADCY5-related movement disorders: Frequency, disease course and phenotypic
      variability in a cohort of paediatric patients.
AB  - INTRODUCTION: ADCY5 mutations have been recently identified as an important cause
      of early-onset hyperkinetic movement disorders. The phenotypic spectrum
      associated with mutations in this gene is expanding. However, the ADCY5
      mutational frequency in cohorts of paediatric patients with hyperkinetic movement
      disorders has not been evaluated. METHODS: We performed a screening of the entire
      ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed
      childhood-onset hyperkinetic movement disorders, featuring chorea alone or in
      combination with myoclonus and dystonia. All patients had normal CSF analysis and
      brain imaging and were regularly followed-up in tertiary centers for paediatric
      movement disorders. RESULTS: We identified five unrelated subjects with ADCY5
      mutations (11% of the cohort). Three carried the p. R418W mutation, one the p.
      R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while
      one patient inherited the mutation from his similarly affected father. All
      patients had delayed motor and/or language milestones with or without axial
      hypotonia and showed generalized chorea and dystonia, with prominent myoclonic
      jerks in one case. Episodic exacerbations of the baseline movement disorder were
      observed in most cases, being the first disease manifestation in two patients.
      The disease course was variable, from stability to spontaneous improvement during
      adolescence. CONCLUSION: Mutations in ADCY5 are responsible for a hyperkinetic
      movement disorder that can be preceded by episodic attacks before the movement
      disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral
      palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance
      are frequently observed in patients with ADCY5 mutations.

PMID- 28511837
TI  - Immunomodulatory activity of recombinant alpha-gliadin conjugated to cholera
      toxin in DQ8 transgenic mice.
AB  - Coeliac disease (CD) is characterized by an intestinal lesion sustained by an
      abnormal mucosal T-cell response to wheat gliadin. An immunological approach that
      is able to suppress this immune response is a perspective worth pursuing. Several
      strategies of antigen administration have been aimed at the downregulation of
      pathogenic T-cells. In particular, we previously reported a significant
      suppression of the systemic cell-mediated response toward wheat gliadin in DQ8
      transgenic mice receiving nasally a recombinant alpha-gliadin. To gain further
      insight about the cellular mechanisms underlying the tolerogenic properties of
      this molecule, we analysed different preparations of the recombinant alpha
      gliadin, alone or conjugated to the adjuvant cholera toxin (CT), by in vitro
      challenge with spleen CD4+ T cells from gliadin-sensitized DQ8 tg mice. We found
      that a partially purified preparation of recombinant alpha-gliadin (r-gliadin)
      induced a significantly higher production of IFN-gamma than native gliadin as
      well as HPLC purified r-gliadin. Interestingly, r-gliadin, but not HPLC purified
      r-gliadin, stimulated the gliadin-specific expression of IL-10 in CD4+ T cells.
      No significant cytotoxic effect was induced by r-gliadin in MODE-K cells, a
      murine model of enterocytes. Notably, a conjugate CT-r-gliadin failed in
      stimulating IFN-gamma, whereas IL-10 secretion was still induced in gliadin
      specific CD4+ T cells. In conclusion, our results showed that DCs, pulsed with CT
      r-gliadin in vitro, could modulate the ongoing Th1-like T cell response toward
      wheat gliadin. This finding provides new insight into the design of
      immunomodulatory protocols potentially useful for CD.

PMID- 28511838
TI  - Supra-annular Valve-in-Valve implantation reduces blood stasis on the
      transcatheter aortic valve leaflets.
AB  - Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and
      Valve-in-Valve (ViV) procedures has been increasingly recognized. This study
      aimed to investigate the effect of positioning of the transcatheter aortic valve
      (TAV) in ViV setting on the flow dynamics aspect of post-ViV thrombosis by
      quantifying the blood stasis in the intra-annular and supra-annular settings. To
      that end, two idealized computational models, representing ViV intra-annular and
      supra-annular positioning of a TAV were developed in a patient-specific geometry.
      Three-dimensional flow fields were then obtained via fluid-solid interaction
      modeling to study the difference in blood residence time (BRT) on the TAV
      leaflets in the two settings. At the end of diastole, a strip of high BRT (?1.2s)
      region was observed on the TAV leaflets in the ViV intra-annular positioning at
      the fixed boundary where the leaflets are attached to the frame. Such a high BRT
      region was absent on the TAV leaflets in the supra-annular positioning. The
      maximum value of BRT on the surface of non-, right, and left coronary leaflets of
      the TAV in the supra-annular positioning were 53%, 11%, and 27% smaller compared
      to the intra-annular positioning, respectively. It was concluded that the
      geometric confinement of TAV by the leaflets of the failed bioprosthetic valve in
      ViV intra-annular positioning increases the BRT on the leaflets and may act as a
      permissive factor in valvular thrombosis. The absence of such a geometric
      confinement in the ViV supra-annular positioning leads to smaller BRT and
      subsequently less likelihood of leaflet thrombosis.

PMID- 28511839
TI  - The implication of the osteolysis threshold and interfacial gaps on
      periprosthetic osteolysis in cementless total hip replacement.
AB  - Osteolysis around joint replacements may develop due to migration of wear
      particles from the joint space into gaps between the interface bone and the
      implant where they can accumulate in high concentrations to cause tissue damage.
      Osteolysis may appear in various postoperative times and morphological shapes
      which can be generalized into linear and focal. However, there are no clear
      explanations on the causes of such variations. Patients' degree of sensitivity to
      polyethylene particles (osteolysis thresholds), the local particle concentration
      and the access route provided by the interface gaps have been described as
      determining factors. To study their effects, a 2D computational fluid dynamics
      model of the hip joint capsule in communication with an interfacial gap and the
      surrounding bone was employed. Particles were presented using a discrete phase
      model (DPM). High capsular fluid pressure was considered as the driving force for
      particle migration. Simulations were run for different osteolysis thresholds
      ranging from 5*108 to 1*1012 particle number per gram of tissue and fibrous
      tissue generation in osteolytic lesion due to particles was simulated for the
      equivalent of ten postoperative years. In patients less sensitive to polyethylene
      particles (higher threshold), osteolysis may be linear and occur along an
      interfacial gap in less than 5% of the interfacial tissue. Focal osteolysis is
      more likely to develop in patients with higher sensitivity to polyethylene
      particles at distal regions to an interfacial gaps where up to 80% of the
      interfacial tissue may be replaced by fibrous tissue. In these patients, signs of
      osteolysis may also develop earlier (third postoperative year) than those with
      less sensitivity who may show very minor signs even after ten years. This study
      shows the importance of patient sensitivity to wear particles, the role of
      interfacial gaps in relation to morphology and the onset of osteolysis.
      Consequently, it may explain the clinically observed variation in osteolysis
      development.

PMID- 28511840
TI  - Quantitative assessment of trunk deformation during running.
AB  - The trunk has a multi-segmental structure and is composed of the cervical,
      thoracic, and lumber spines and surrounding soft tissue elements; this allows
      flexible deformation during dynamic movements. The purpose of this study was to
      quantitatively assess trunk deformation during dynamic movement. Ten male
      subjects performed running at four different speeds: 8km/h, 10km/h, 12km/h, and
      14km/h. Forty reflective markers were placed on the backs of these individuals to
      define 56 small triangular areas, and three-dimensional kinematic data was
      recorded with a motion capture system. The coefficients of variation (CV) of the
      horizontal and vertical lengths between two adjacent markers and the standard
      deviation (SD) of the normal vectors of triangular areas were calculated as
      measures for translational and angular trunk deformation, respectively. Up to
      about 14% of CV and 78 degrees  of SD appeared as the measure of translational
      and angular deformation, respectively. These results imply that the trunk
      underwent a significant amount of position-specific deformation. These findings
      would be useful in the construction of an optimal trunk segment model to
      represent the complex and flexible trunk movement during dynamic movements.

PMID- 28511841
TI  - A method for isolating cortical interneurons sharing the same birthdays for gene
      expression studies.
AB  - The two neuronal populations in the cortex, pyramidal neurons and interneurons,
      can be separated based on neurotransmitter identity, however, within this
      segregation a large degree of diversity exists. Investigations into the molecular
      diversity of neurons are impeded by the inability to isolate cell populations
      born at different times for gene expression analysis. Developing interneurons may
      be distinguished by the expression of Glutamic Acid Decarboxylase-67 (GAD67).
      Neuronal birthdating using nucleoside analogs is an effective means of
      identifying coetaneous interneurons. Using these two features, neurotransmitter
      identity and birthdating, we have developed a method to isolate migrating
      interneurons using fluorescent-activated cell sorting (FACS) for RNA extraction
      and gene expression analysis. We utilized 5-ethynyl-2'-deoxyuridine (EdU) to
      birthdate interneuron cohorts and the GAD67 knock-in GFP transgenic mice to
      identify interneurons. In combination, we achieved simultaneous detection of GFP
      and EdU signals during FACS sorting of coetaneous interneurons with minimum loss
      of RNA integrity. RNA quality was deemed to be satisfactory by quantitative
      polymerase chain reaction (qPCR) for the interneuron-specific transcript Gad67.

PMID- 28511842
TI  - Response to the letter to the editor regarding "Quantitative study of voice
      dysfunction after thyroidectomy".

PMID- 28511843
TI  - Interpellating recovery: The politics of 'identity' in recovery-focused
      treatment.
AB  - Much research tends to treat alcohol and other drug 'recovery' as a process of
      positive identity change and development. In this article, we depart from this
      dominant approach by examining how the social and material practices of alcohol
      and other drug treatment are themselves active in the constitution of 'recovery
      identity'. Using Judith Butler's theorisation of interpellation, we examine the
      accounts of treatment experiences and practices provided in interviews with
      people who inject drugs. In contrast to the existing literature, we argue that
      the 'recovering addict' is a socially produced category rather than a coherent
      psychological identity. We consider the production of this category in relation
      to three dynamics identified in the data: (1) the tendency to materialise
      treatment subjects as both disordered and as 'in control' of these disorders; (2)
      the production of treatment subjects as enmeshed in suspect social relationships
      and therefore requiring surveillance as well as social support; and (3)
      treatment's particular enactment of social context such that it erases
      stigmatisation and marginalisation and paradoxically performs subjects as
      entirely individually responsible for relinquishing drug use. These dynamics
      produce capacities and attributes often ascribed to identity but which are better
      understood as articulations of epistemological disorder in the state of knowledge
      about addiction, and its expression in treatment. By way of conclusion, we
      question the utility of 'recovery identity', conventionally defined, in providing
      a rationale for treatment.

PMID- 28511844
TI  - Pediatric Nurse Practitioners in the Emergency Department: Implications for
      Education and Research.
AB  - The use of pediatric nurse practitioners in emergency departments is common in
      the United States. Defining competencies that are specific to the wide span of
      urgent and emergent pediatric conditions, along with a recognized practice
      standard for education and specialty certification for pediatric nurse
      practitioners practicing in emergency care, is needed. Pediatric emergency
      departments require a team of providers with a skill set that aligns with each
      patient's needs. The use of qualified pediatric nurse practitioners on these
      teams, both primary care and acute care certified, to provide care to these
      children is expanding, with implications for education and research.

PMID- 28511845
TI  - miR-205 is a critical regulator of lacrimal gland development.
AB  - The tear film protects the terrestrial animal's ocular surface and the lacrimal
      gland provides important aqueous secretions necessary for its maintenance.
      Despite the importance of the lacrimal gland in ocular health, molecular aspects
      of its development remain poorly understood. We have identified a noncoding RNA
      (miR-205) as an important gene for lacrimal gland development. Mice lacking miR
      205 fail to properly develop lacrimal glands, establishing this noncoding RNA as
      a key regulator of lacrimal gland development. Specifically, more than half of
      knockout lacrimal glands never initiated, suggesting a critical role of miR-205
      at the earliest stages of lacrimal gland development. RNA-seq analysis uncovered
      several up-regulated miR-205 targets that may interfere with signaling to impair
      lacrimal gland initiation. Supporting this data, combinatorial epistatic deletion
      of Fgf10, the driver of lacrimal gland initiation, and miR-205 in mice
      exacerbates the lacrimal gland phenotype. We develop a molecular rheostat model
      where miR-205 modulates signaling pathways related to Fgf10 in order to regulate
      glandular development. These data show that a single microRNA is a key regulator
      for early lacrimal gland development in mice and highlights the important role of
      microRNAs during organogenesis.

PMID- 28511846
TI  - Measuring the differences in work ratios between pediatric and adult
      ophthalmologic examinations.
AB  - PURPOSE: To assess the differences in work needed for pediatric and adult
      ophthalmologic examinations. METHODS: Seven ophthalmology residents conducted
      slit-lamp and refraction examinations on children 3-7 years of age and adults 20
      69 years of age. The examiners reported the magnitude estimate (ME) of their work
      in relation to two references (cross-reference ME): average adult examination and
      average pediatric examination. The examination time was also measured. RESULTS:
      For the slit-lamp examination, 50 children and 58 adults were recruited. The ME
      was 1.45 (95% CI, 1.30-1.62) times higher for the pediatric examinations than for
      the adult examinations when the reference was an average adult case. With respect
      to time, the pediatric examinations took 1.22 (95% CI, 1.06-1.41) times longer
      than the adult examinations. For the refraction examinations, 58 children and 96
      adults were recruited. The ME was 1.35 (95% CI, 1.21-1.52) times higher for the
      pediatric examinations. The pediatric examination took 1.32 (95% CI, 1.16-1.50)
      times longer than the adult examination. The cross-reference ME ratios measuring
      the pediatric over adult examinations against both the pediatric and adult
      reference cases were equivalent in both the slit-lamp and the refraction
      examinations; however, the ME and time ratios of the pediatric over the adult
      examinations were not equivalent for the slit-lamp or for the refraction
      examinations. CONCLUSIONS: The cross-reference ME showed that pediatric
      ophthalmologic examinations require more work than the adult examination with
      validity and reliability. The time estimate was insufficient as a single
      indicator for work estimation.

PMID- 28511847
TI  - Moving with the times.

PMID- 28511848
TI  - Intense resistance exercise increases peripheral brain-derived neurotrophic
      factor.
AB  - OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been shown to increase
      in an intensity dependent manner in response to aerobic exercise. However,
      previous research investigating the use of resistance exercise to increase BDNF
      levels has been less conclusive, likely due to the low intensity nature of
      traditional resistance exercise programs. This study examined the influence of
      acute resistance exercise to-fatigue on serum BDNF levels and blood lactate.
      DESIGN: Acute crossover study. METHODS: Eleven untrained to intermediately
      trained males (age: 25.0+/-1.3 year) and five untrained females (age: 23.2+/-1.1
      year) were recruited to undertake two bouts of resistance exercise. Strength
      (five sets of five repetitions, 180s recovery) and hypertrophy (three sets of ten
      repetitions, 60s recovery) based resistance exercise was implemented to-fatigue
      to examine the effect on serum BDNF and blood lactate levels immediately post-,
      and 30min post-exercise. RESULTS: An interaction (p<0.01; ES=0.52) was observed
      between conditions immediately post-exercise, with hypertrophy resulting in
      significantly greater BDNF levels when compared with strength exercise. Changes
      in lactate and BDNF from baseline to post- exercise were positively correlated
      following hypertrophy exercise (r=0.70; p<0.01), but not correlated following
      strength exercise (r=0.18; p=0.56). CONCLUSIONS: The use of a to-fatigue
      hypertrophy based resistance exercise protocol provides the necessary stimulus to
      increase peripheral serum BDNF. Mechanistically, the presence of lactate does not
      appear to drive the BDNF response during resistance exercise.

PMID- 28511849
TI  - Cardiometabolic healthy obesity paradigm and all-cause mortality risk.
AB  - OBJECTIVE: To examine the cardiometabolic healthy obesity paradigm as it relates
      to all-cause mortality risk, with effect moderation evaluated for physical
      activity and demographic characteristics. METHODS: Data from the 1999-2006 NHANES
      were used. The analytic sample included 7579 dietary fasting adults (20+ yrs).
      All-cause mortality was linked with participant data from the National Death
      Index. Metabolic health was based on fasting levels of triglycerides, high
      density lipoprotein cholesterol, glucose and blood pressure. Weight status was
      determined from measured height and weight. Physical activity was assessed via
      self-report. Six mutually exclusive groups were evaluated, including 1)
      Metabolically Healthy and Normal Weight (Referent), 2) Metabolically Healthy and
      Overweight, 3) Metabolically Healthy and Obese, 4) Metabolically Abnormal and
      Normal Weight, 5) Metabolically Abnormal and Overweight, and 6) Metabolically
      Abnormal and Obese. A Cox proportional hazards model was used to evaluate the
      association between these 6 groups and all-cause mortality. RESULTS: The
      unweighted median follow-up was 103months; 770,568 person-months occurred with an
      incidence rate of 1.18 deaths per 1000 person-months. When compared to those who
      were metabolically healthy and of normal BMI, all other metabolic and weight
      configurations had an increased mortality risk. There was no evidence of effect
      modification by physical activity or demographic characteristics. CONCLUSIONS:
      These findings emphasize the importance of optimizing body habitus and increasing
      public awareness of the detrimental effects of metabolic abnormalities.

PMID- 28511850
TI  - Asteroid Hyalosis.

PMID- 28511851
TI  - Sex differences in association between decreased glomerular filtration rate and
      prolongation of corrected QT interval in general Chinese population.

PMID- 28511852
TI  - Introducing a checking technician allows pharmacists to spend more time on
      patient-focused activities.
AB  - BACKGROUND: Internationally there is an increasing focus on the clinical and
      cognitive services that pharmacists can provide. Lack of time has been identified
      as a barrier to pharmacists increasing their clinical activities. Within the
      pharmacy workplace there are many tasks that can only be performed by a
      pharmacist. The final accuracy check of a dispensed prescription is currently the
      sole responsibility of pharmacists in New Zealand. This takes up a significant
      amount of time during a pharmacist's work day. The introduction of a checking
      technician role has been suggested to allow pharmacists more time to do more
      patient focused work. AIM/OBJECTIVE: To investigate the amount of time pharmacy
      staff spend on specific activities and to establish whether the introduction of a
      checking technician into twelve pilot sites increased the amount of time that the
      pharmacists could spend on patient focused activities. METHODS: This study
      utilised a self-reported work sampling technique in twelve pilot sites, selected
      from both the hospital and community settings. Work sampling using an electronic
      device was conducted at two time-points (before the implementation of a Pharmacy
      Accuracy Checking Technician (PACT) role and when the PACT was in place). Data
      was collected at 10 min intervals for the period of five days, a working week.
      Tasks were grouped into patient focused, dispensing and personal activities.
      RESULTS: The introduction of the PACT into the pilot sites saw a mean increase of
      19% in pharmacists' patient focused activities and a mean 20% decrease in
      dispensing activities. CONCLUSION: The introduction of a checking technician role
      into New Zealand pharmacies demonstrated the potential to provide pharmacists
      with more time to spend on patient focused activities.

PMID- 28511853
TI  - Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens
      against highly pathogenic avian influenza virus.
AB  - Avian influenza viruses (AIV) are a threat to poultry production worldwide.
      Vaccination is utilized as a component of control programs for both high
      pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine
      used in poultry are inactivated, adjuvanted products. To identify the best
      formulations for chickens, vaccines were prepared with beta-propiolactone (BPL)
      inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially
      available or experimental adjuvants. Each vaccine formulation was evaluated for
      immunogenicity in chickens. Challenge studies with an antigenically homologous
      strain of HPAIV were conducted to compare protection against mortality and
      measure reductions in virus levels in oral swabs. The four best adjuvants from
      the studies with BPL inactivated antigen were selected and tested identically,
      but with vaccines prepared from formalin inactivated virus. Mineral and vegetable
      oil based adjuvants generally induced the highest antibody titers with 100%
      seroconversion by 3weeks post vaccination. Chitosan induced positive antibody
      titers in 100% of the chickens, but the titers were significantly lower than
      those of most of the oil based adjuvants. Antibody levels from calcium phosphate
      and alginate adjuvanted groups were similar to those of non-adjuvanted virus. All
      groups that received adjuvanted vaccines induced similar levels of protection
      against mortality (0-20%) except the groups vaccinated with calcium phosphate
      adjuvanted vaccines, where mortality was similar (70%) to groups that received
      non-adjuvanted inactivated virus or no vaccine (60-100% mortality). Virus
      shedding in oral swabs was variable among the treatment groups. Formalin
      inactivated vaccine induced similar antibody titers and protection against
      challenge compared to BPL inactivated vaccine groups. These studies support the
      use of oil adjuvanted vaccines for use in the poultry industry for control for
      AIV.

PMID- 28511854
TI  - Acot1 is a sensitive indicator for PPARalpha activation after perfluorooctanoic
      acid exposure in primary hepatocytes of Sprague-Dawley rats.
AB  - Perfluorooctanoic acid (PFOA) is one of the most commonly detected and persistent
      perfluoroalkyl substances (PFASs) found in the environment. We found that cell
      viability and intracellular oxidant stress increased in primary rat hepatocytes
      exposed to PFOA (100MUM PFOA, 24h), and mitochondrial superoxide increased from
      6.25MUM PFOA treatment group. To screen for sensitive indicators in mRNA level,
      we investigated global transcriptome profile alteration after PFOA exposure using
      RNA-sequencing (RNA-seq) in primary rat hepatocytes, and identified 177 gene
      transcripts (158 upregulated, 19 downregulated) as significantly changed after
      exposure to 100MUM of PFOA for 24h (fold change >=2, FDR<0.05). Quantitative PCR
      (qPCR) and RNA-fluorescence in situ hybridization (RNA-FISH) assays were
      conducted after PFOA treatment at various doses (0, 0.4, 1.56, 6.25, 25, and
      100MUM) and times (6, 12, 18, 24, 48, and 96h). Acot1 transcripts increased
      significantly in the 100MUM PFOA group (4500-fold) after 24h of exposure, and
      increased remarkably for all time points (24, 48, 72 and 96h) after exposure to
      6.25MUM. Acot1 also responded to lower PFOA doses, with a significant increase
      found after exposure to 0.4MUM for 96h. These results imply Acot1 could serve as
      a sensitive indicator for PPARalpha activation after PFOA exposure in primary rat
      hepatocytes.

PMID- 28511856
TI  - Measurement of 15N longitudinal relaxation rates in 15NH4+ spin systems to
      characterise rotational correlation times and chemical exchange.
AB  - Many chemical and biological processes rely on the movement of monovalent cations
      and an understanding of such processes can therefore only be achieved by
      characterising the dynamics of the involved ions. It has recently been shown that
      15N-ammonium can be used as a proxy for potassium to probe potassium binding in
      bio-molecules such as DNA quadruplexes and enzymes. Moreover, equations have been
      derived to describe the time-evolution of 15N-based spin density operator
      elements of 15NH4+ spin systems. Herein NMR pulse sequences are derived to select
      specific spin density matrix elements of the 15NH4+ spin system and to measure
      their longitudinal relaxation in order to characterise the rotational correlation
      time of the 15NH4+ ion as well as report on chemical exchange events of the
      15NH4+ ion. Applications to 15NH4+ in acidic aqueous solutions are used to cross
      validate the developed pulse sequence while measurements of spin-relaxation rates
      of 15NH4+ bound to a 41kDa domain of the bacterial Hsp70 homologue DnaK are
      presented to show the general applicability of the derived pulse sequence. The
      rotational correlation time obtained for 15N-ammonium bound to DnaK is similar to
      the correlation time that describes the rotation about the threefold axis of a
      methyl group. The methodology presented here provides, together with the previous
      theoretical framework, an important step towards characterising the motional
      properties of cations in macromolecular systems.

PMID- 28511855
TI  - Clinical correlates and prognostic impact of impaired iron storage versus
      impaired iron transport in an international cohort of 1821 patients with chronic
      heart failure.
AB  - AIMS: To define iron deficiency in chronic heart failure (CHF), both,
      ferritin<100MUg/L (indicating reduced iron storage) and transferrin saturation
      (TSAT)<20% (indicating reduced iron transport) are used. The aim of the study was
      to evaluate clinical outcomes and prognosis of either low ferritin or low TSAT in
      patients with CHF. METHODS AND RESULTS: We evaluated the clinical impact of
      impaired iron storage (IIS) and impaired iron transport (IIT) either alone or in
      combination compared to patients with normal iron status (NIS), in an
      international cohort of 1821 patients with CHF with a mean age of 66+/-13years
      and mean left ventricular ejection fraction of 35%+/-15. Isolated IIS was
      observed in 219 patients (12%), isolated IIT in 454 (25%) and coexistence of both
      conditions (IIS+IIT) were seen in 389 (21%). In adjusted models we found that
      patients with IIS+IIT and patients with isolated IIT had higher NT-proBNP levels
      (OR 2.2 [1.6-3.1] and OR 2.1 [1.5-2.9] respectively) and worse quality of life
      (OR 1.8 [1.2-2.7] and OR 1.7 [1.2-2.5] respectively) compared with isolated IIS.
      Multivariate Cox analyses showed that IIS+IIT and isolated IIT were independently
      associated with all-cause mortality (OR 1.41 [1.06-1.86] and OR 1.47 [1.13-1.92]
      respectively). Patients with isolated IIS did not differ from NIS patients in
      terms of severity or outcomes. CONCLUSIONS: Impaired iron transport alone or in
      combination with impaired iron storage is associated with worse clinical profile
      and increased risk of mortality in patients with CHF. Patients with isolated
      impaired iron storage may have a milder form of iron deficiency.

PMID- 28511857
TI  - Posterior microphthalmos, retinitis pigmentosa and optic disc drusen with white
      dots. A case report.
AB  - OBJECTIVE: To present the case of a patient with a posterior microphthalmos-optic
      disc drusen-retinitis pigmentosa syndrome associated, for the first time, with
      white dots in the posterior pole. METHODOLOGY: The posterior microphthalmos,
      retinitis pigmentosa and optic disc drusen syndrome was described for the first
      time in literature in 1991. Later, it was associated with a pattern of foveal
      thickening and/or foveoschisis. Different forms of mutations on chromosomes 11
      and 14 have been identified as being responsible for the appearance of this
      syndrome, but the inheritance pattern is unknown. DISCUSSION: The case is
      reported of a 37 year-old man, with no personal or family history of interest,
      diagnosed with this syndrome in association with white dots in the posterior
      pole. Such a morphological association has never been published before in
      literature. CONCLUSION: The posterior microphthalmos, retinitis pigmentosa and
      optic disc drusen syndrome is a very rare entity, and has never been described
      associated with white dots in the posterior pole. More case reports are needed to
      establish clear patterns of both the disease and inheritance.

PMID- 28511860
TI  - First-Trimester Fetal Echocardiography: Identification of Cardiac Structures for
      Screening from 6 to 13 Weeks' Gestational Age.
AB  - BACKGROUND: Early fetal echocardiography (FE), performed at 12 to 16 weeks'
      gestational age (GA), can be used to screen for fetal heart disease akin to that
      routinely performed in the second trimester. The efficacy of FE at earlier GAs
      has not been as well explored, particularly with recent advances in ultrasound
      technology. The aim of this study was to evaluate the efficacy of early FE in
      assessing fetal heart structure, and the added benefit of color Doppler (CD),
      from as early as 6 weeks through to 13+6 weeks' GA. METHODS: Pregnant women were
      prospectively recruited for first-trimester FE. All underwent two-dimensional
      (2D) cardiac imaging combined with CD assessment, and all were offered second
      trimester fetal echocardiographic evaluations. Fetal cardiac anatomy was assessed
      both in real time during FE and additionally offline by two separate reviewers.
      RESULTS: Very early FE was performed in 202 pregnancies including a total of 261
      fetuses, with 92% (n = 241) being reassessed at >=18 weeks' GA. Mean GA at FE was
      10+6 weeks (range, 6+1 to 13+6 weeks). Transabdominal scanning was used in all
      cases, and transvaginal scanning was used additionally in most at <11 weeks' GA
      (n = 103 of 117 [88%]). There was stepwise improvement in image resolution of the
      fetal heart in those pregnancies that presented at later gestation for
      assessment. CD assisted with definition of cardiac anatomy at all GAs. A four
      chambered heart could be identified in 52% of patients in the eighth week (n = 12
      of 23), improving to 80% (n = 36 of 45) in the 10th week and 98% (n = 57 of 58)
      by the 11th week. The inferior vena cava was visualized by 2D imaging in only 4%
      (n = 1 of 23) in the eighth week, increasing to 13% (n = 6 of 45) by the 10th
      week and 80% (n = 25 of 31) by the 13th week. CD improved visualization of the
      inferior vena cava at earlier GAs to >80% (n = 37 of 45) from 10 weeks. Pulmonary
      veins were not visualized by either 2D imaging or CD until after the 11th week.
      Both cardiac outflow tracts could be visualized by 2D imaging in the minority
      from 8+0 to 10+6 weeks (n = 18 of 109 [16%]) but were imaged in most from 11+0 to
      13+6 weeks (n = 114 of 144 [79%]). CD imaging improved visualization of both
      outflow tracts to 64% (n = 29 of 45) in the 10th week. On 2D imaging alone, both
      the aortic and ductal arches were seen in only 29% of patients in the 10th week
      (n = 13 of 45), increasing to 58% when CD was used (58% [n = 26 of 45]) and to
      >80% (n = 47 of 58) using CD in the 11th week. CONCLUSIONS: Very early FE, from
      as early as 8 weeks, can be used to assess cardiac structures. The ability to
      image fetal heart structures between 6 and 8 weeks is currently nondiagnostic.
      The use of CD significantly increases the detection of cardiac structures on
      early FE. The ideal timing of complete early FE, excluding pulmonary vein
      assessment, appears to be after 11 weeks' GA.

PMID- 28511859
TI  - Reference Ranges and Regional Patterns of Left Ventricular Strain and Strain Rate
      Using Two-Dimensional Speckle-Tracking Echocardiography in a Healthy Middle-Aged
      Black and White Population: The CARDIA Study.
AB  - BACKGROUND: Strain and strain rate are sensitive markers of left ventricular (LV)
      myocardial function. The aim of this study was to assess reference ranges and
      regional patterns of LV strain and strain rate using two-dimensional speckle
      tracking echocardiography in a large population of black and white subjects.
      METHODS: This study involved a retrospective review of prospectively collected
      images in 557 participants in the Coronary Artery Risk Development in Young
      Adults study who remained healthy at the year 25 examination. LV deformation
      parameters were measured in apical four-chamber, apical two-chamber, and
      parasternal short-axis views in 509, 391, and 521 subjects, respectively.
      RESULTS: Patients' mean age was 49.6 +/- 3.6 years, 61.6% were women, and 69.5%
      were white. White women showed the highest LV systolic and diastolic deformation
      values, reflected by a more negative reference range for apical four-chamber
      longitudinal strain (-16.4%; 95% prediction interval [PI], -20.8% to -12.0%) and
      a higher positive reference range for early diastolic strain rate (0.93 1/sec;
      95% PI, 0.41 to 1.46 1/sec), respectively. The lowest LV systolic and diastolic
      deformation values were found in black men, with apical four-chamber longitudinal
      strain (14.7%; 95% PI, -19.1% to -10.3%) and early diastolic strain rate (0.79
      1/sec; 95% PI, 0.42 to 1.16 1/sec). Absolute strain increased from the epicardium
      toward the endocardium. A base-to-apex gradient of longitudinal strain toward the
      apex was exhibited in inferior and inferoseptal regions and, in contrast, in the
      opposite direction in anterior and anterolateral walls. Sex had the strongest
      influence on LV deformation variability. CONCLUSIONS: Strain and strain rate
      reference values were sex and race related. White women showed the highest
      reference ranges for LV deformation, while the lowest values were found in black
      men. Significant layer- and level-specific patterns in regional LV deformation
      were identified.

PMID- 28511861
TI  - Speckle-Tracking Layer-Specific Analysis of Myocardial Deformation and Evaluation
      of Scar Transmurality in Chronic Ischemic Heart Disease.
AB  - BACKGROUND: Identification of the extent of scar transmurality in chronic
      ischemic heart disease is important because it correlates with viability. The aim
      of this retrospective study was to evaluate whether layer-specific two
      dimensional speckle-tracking echocardiography allows distinction of scar presence
      and transmurality. METHODS: A total of 70 subjects, 49 with chronic ischemic
      cardiomyopathy and 21 healthy subjects, underwent two-dimensional speckle
      tracking echocardiography and late gadolinium-enhanced cardiac magnetic
      resonance. Scar extent was determined as the relative amount of hyperenhancement
      using late gadolinium-enhanced cardiac magnetic resonance in an 18-segment model
      (0% hyperenhancement = normal; 1%-50% = subendocardial scar; 51%-100% =
      transmural scar). In the same 18-segment model, peak systolic circumferential
      strain and longitudinal strain were calculated separately for the endocardial and
      epicardial layers as well as the full-wall myocardial thickness. RESULTS: All
      strain parameters showed cutoff values (area under the curve > 0.69) that allowed
      the discrimination of normal versus scar segments but not of transmural versus
      subendocardial scars. This was true for all strain parameters analyzed, without
      differences in efficacy between longitudinal and circumferential strain and
      subendocardial, subepicardial, and full-wall-thickness strain values.
      Circumferential and longitudinal strain in normal segments showed transmural and
      basoapical gradients (greatest values at the subendocardial layer and apex). In
      segments with scar, transmural gradient was maintained, whereas basoapical
      gradient was lost because the reduction of strain values in the presence of the
      scar was greater at the apex. CONCLUSIONS: The two-dimensional speckle-tracking
      echocardiographic values distinguish scar presence but not transmurality; thus,
      they are not useful predictors of scar segment viability. It remains unclear why
      there is a greater strain value reduction in the presence of a scar at the apical
      level.

PMID- 28511858
TI  - Reduced Myocardial Reserve in Young X-Linked Muscular Dystrophy Mice Diagnosed by
      Two-Dimensional Strain Analysis Combined with Stress Echocardiography.
AB  - BACKGROUND: Early, sensitive, and reproducible evaluation of left ventricular
      function is imperative for the diagnosis of cardiac dysfunction in patients with
      Duchene muscular dystrophy. The aim of this study was to test the hypothesis that
      combining two-dimensional strain analysis with catecholamine stress could be a
      sensitive method for detecting early cardiac dysfunction. METHODS: Mdx
      (C57BL/10ScSn-Dmdmdx/J, a mouse model of DMD) and control (C57BL/10ScSn) mice
      were studied with conventional M-mode and high-frequency ultrasound-based two
      dimensional speckle-tracking echocardiography using long- and short-axis images
      of the left ventricle at baseline and after intraperitoneal isoprenaline (ISO)
      administration (2 MUg/g body weight). RESULTS: Conventional M-mode analysis
      showed no differences in left ventricular fractional shortening, wall thickness,
      or internal diameter at diastole between mdx and control mice before the age of 6
      months. ISO increased left ventricular ejection fraction and fractional
      shortening to the same extent in mdx and control mice at young ages (3, 4, and 5
      months). No differences in basal peak systolic strain (PSS) but increased SDs of
      times to PSS between young mdx and control mice were found. After ISO, PSS and
      percentile changes of PSS were significantly diminished in mdx mice compared with
      control mice at young ages. ISO increased the normalized maximum difference of
      times to PSS in young mdx mice but not in young control mice, suggesting that ISO
      reduces cardiac contractile synchrony in young mdx mice. CONCLUSIONS: This study
      suggests that catecholamine stress coupled with two-dimensional strain analysis
      is a feasible and sensitive approach for detecting early onset of cardiac
      dysfunction, which is instrumental for early diagnosis of cardiac dysfunction and
      early treatment.

PMID- 28511862
TI  - Effect of different concentrations of egg yolk and virgin coconut oil in Tris
      based extenders on chilled and frozen-thawed bull semen.
AB  - The aim of this study was to evaluate the effects of 8% virgin coconut oil (VCO)
      combined with different percentages of egg yolk in Tris extender on the quality
      of chilled and frozen-thawed bull semen. A total of 24 ejaculates from four bulls
      were collected using an electroejaculator. Semen samples were diluted with 8% VCO
      in Tris extender which contained different concentrations 0% (control), 4%, 8%,
      12%, 16% and 20% egg yolk. The diluted semen samples were divided into two
      fractions: one was chilled and stored at 4 degrees C until evaluation after 24,
      72, and 144h; the second fraction was processed by chilling for 3h at 4 degrees C
      to equilibrate, then packaged in 0.25ml straws and frozen and stored in liquid
      nitrogen at -196 degrees C until evaluation after 7 and 14 days. Both chilled and
      frozen semen samples were then thawed at 37 degrees C and assessed for general
      motility using computer-assisted semen analysis (CASA), viability, acrosome
      integrity, and morphology (eosin-nigrosin), membrane integrity (hypo-osmotic
      swelling test) and lipid peroxidation (thiobarbituric acid-reactive substances
      (TBARS)). The results indicate treatments with 8%, 12%, 16% and 20% egg yolk with
      8% VCO had greater sperm quality (P<0.05) as compared with the control. The
      treatment with 20% egg yolk had the greatest sperm quality (P<0.05) among the
      treated groups for both chilled and frozen-thawed semen. In conclusion, the use
      of 8% VCO combined with 20% egg yolk in a Tris-based extender enhanced the values
      for chilled and frozen-thawed quality variables of bull sperm.

PMID- 28511863
TI  - Expression of TNF-alpha system members in bovine ovarian follicles and the
      effects of TNF-alpha or dexamethasone on preantral follicle survival, development
      and ultrastructure in vitro.
AB  - This study was conducted to detect the protein expression of TNF-alpha system
      members (TNF-alpha/TNFR1/TNFR2) in bovine ovarian follicles and to evaluate the
      effects of TNF-alpha or dexamethasone on the survival and growth of primordial
      follicles in vitro, as well as on gene expression in cultured ovarian tissue. It
      was hypothesized that TNF-alpha induces follicular atresia in ovarian tissues
      cultured in vitro, and that dexamethasone suppresses the production of endogenous
      TNF-alpha, which can improve follicle viability in vitro. Ovarian fragments were
      cultured for 6days in alpha-MEM+ supplemented with TNF-alpha (0, 1, 10, 100 or
      200ng/ml) or dexamethasone (0, 1, 10, 100 or 200ng/ml). After culture, the
      expression of mRNAs for BCL-2, BAX, P53, TNF-alpha, and CASP3 and CASP6 were
      evaluated. Immunohistochemical results showed that the TNF-alpha system members,
      were detected in bovine preantral and antral follicles. After 6days, the TNF
      alpha (10ng/ml) treatment reduced the percentage of normal preantral follicles
      and increased the number of TUNEL-positive cells in cultured tissue.
      Dexamethasone (10ng/ml) during 6days of culture did maintain the percentage of
      normal follicles and the ultrastructure of follicles, while the presence of TNF
      alpha or dexamethasone did not influence primordial follicle activation. However,
      TNF-alpha or dexamethasone had no effect on the levels of mRNA for P53, BCL-2,
      BAX and CASP6, in cultured tissues, but the presence of dexamethasone reduced the
      levels of CASP3 compared to ovarian slices cultured in control medium (alpha
      MEM+). In conclusion, proteins of the TNF-alpha system are expressed at different
      bovine follicle stages. The addition of TNF-alpha in culture reduces follicle
      survival and increases the number of apoptotic cells in ovarian tissue, while the
      presence of dexamethasone maintains follicle ultrastructure in cultured tissue.

PMID- 28511864
TI  - Metabolism and disposition of [14C]-methylcyclosiloxanes in rats.
AB  - Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) are low
      molecular weight cyclic volatile methyl siloxanes (cVMSs) primarily used as
      intermediates or monomers in the production of high molecular weight silicone
      polymers. The use of D4 as a direct ingredient in personal care products has
      declined significantly over the past 20 years, although it may be present as a
      residual impurity in a variety of consumer products. D5 is still used as an
      intentional ingredient in cosmetics, consumer products and in dry cleaning.
      Persons who may be exposed include occupational exposure for workers, and
      potential inhalation or dermal exposure for consumers and the general public.
      Because of the diverse use, especially of D5, and the potential for human
      exposure, a comprehensive program was undertaken to understand the kinetics,
      metabolism, enzyme induction and toxicity of D4 and D5 in rats following relevant
      routes of exposure. Physiologically based pharmacokinetic (PBPK) models utilizing
      these studies have been reported for D4 and D5 in the rat and human following
      dermal and inhalation exposures, with the oral uptake component of the model
      being limited in its description. Data from high dose oral studies in corn oil
      and simethicone vehicles and neat were used in the D4/D5 harmonized PBPK model
      development. It was uncertain if the inability to adequately describe the oral
      uptake was due to unrealistic high doses or unique aspects of the chemistry of
      D4/D5. Low dose studies were used to provide data to refine the description of
      oral uptake in the model by exploring the dose dependency and the impact of a
      more realistic food-like vehicle. Absorption, distribution, metabolism and
      elimination (ADME) of D4 and D5 was determined following a single low oral gavage
      dose of 14C-D4 and 14C-D5 at 30 and 100mg/kg body weight (bw), respectively, in a
      rodent liquid diet. Comparison of the low vs. high dose oral gavage
      administration of D4 and D5 demonstrated dose-dependent kinetic behavior. Data
      and modeling results suggest differences in metabolism between low and high dose
      administration indicating high dose administration results in or approaches non
      linear saturated metabolism. These low dose data sets were used to refine the
      D4/D5 multi-route harmonized PBPK model to allow for a better description of the
      disposition and toxicokinetics of D4/D5 following oral exposure. With a refined
      oral uptake description, the model could be used in risk assessment to better
      define the internal dose of D4 and D5 following exposure to D4 and D5 via
      multiple routes.

PMID- 28511865
TI  - Racial and socioeconomic disparities in viral suppression among persons living
      with HIV in New York City.
AB  - PURPOSE: To examine differences in racial disparities across levels of
      neighborhood poverty and differences in socioeconomic disparities by
      race/ethnicity in viral suppression among persons living with HIV (PLWH).
      METHODS: Using HIV surveillance data, we categorized and geocoded PLWH who were
      in care in New York City (NYC). Multilevel binomial regression techniques were
      used to model viral suppression with a two-level hierarchical structure, by
      including age, transmission risk, year of diagnosis, race/ethnicity, census tract
      poverty, and an interaction term of race/ethnicity and census tract poverty in
      the model. RESULTS: There were 30,638 Blacks, 22,921 Hispanics, and 11,695 Whites
      living with HIV and retained in care in NYC, 2014. Compared with Blacks living in
      the most impoverished neighborhoods (>=30% residents living below the federal
      poverty level) who had the lowest proportion of viral suppression, with 75% in
      males and 76% in females, Whites living in the least impoverished neighborhoods
      (<10% residents living below the federal poverty level) had the highest, with 92%
      in males (prevalence ratio = 1.16; 95% confidence interval: 1.13, 1.18) and 90%
      in females (PR = 1.14; 95% CI: 1.09, 1.19). CONCLUSIONS: By examining racial and
      socioeconomic disparities simultaneously, we were able to detect both disparities
      in viral suppression among PLWH in NYC.

PMID- 28511866
TI  - Differences in mental health among young adults with borderline personality
      symptoms of various severities.
AB  - PURPOSE: This study examined the differences in mental health and behavioral
      problems among young adults with borderline personality symptoms of various
      severities. METHODS: 500 college students participated in this study. Borderline
      personality symptoms were evaluated using the Taiwanese version of the Borderline
      Symptom List (BSL-23). Mental health problems were assessed using the Symptom
      Checklist-90-Revised Scale. Suicidality and other behavioral problems were
      assessed using questions from the epidemiological version of the Kiddie Schedule
      for Affective Disorders and Schizophrenia and BSL-23 Supplement. According to the
      distribution of BSL-23 scores at the 25th, 50th, and 75th percentiles, the
      participants were divided into 4 groups: No/Mild, Moderate, Severe, and Profound.
      Analysis of variance and the chi-square test were used to compare mental health
      and behavioral problems among the 4 groups. RESULTS: All mental health problems
      differed significantly among the 4 groups. The severity of nearly all mental
      health problems increased with that of borderline personality symptoms. The
      proportions of most behavioral problems differed significantly among the 4
      groups. The Profound group was more likely to have behavioral problems than the
      other 3 groups. CONCLUSION: Young adults who had more severe borderline
      personality symptoms had more severe mental health and behavioral problems.

PMID- 28511867
TI  - Social housing and social isolation: Impact on stress indices and energy balance
      in male and female Syrian hamsters (Mesocricetus auratus).
AB  - Although Syrian hamsters are thought to be naturally solitary, recent evidence
      from our laboratory demonstrates that hamsters may actually prefer social
      contact. Hamsters increase their preference for a location associated with an
      agonistic encounter regardless of whether they have "won" or "lost". It has also
      been reported that social housing as well as exposure to intermittent social
      defeat or to a brief footshock stressor increase food intake and body mass in
      hamsters. By contrast, it has also been suggested that housing hamsters in social
      isolation causes anxiety-induced anorexia and reductions in body mass selectively
      in females. The purpose of this study was to determine the physiological
      consequences of housing hamsters in social isolation versus in social groups.
      Male and female hamsters were housed singly or in stable groups of 5 for 4weeks
      after which they were weighed and trunk blood was collected. In addition, fat
      pads and thymus and adrenal glands were extracted and weighed. Serum and fecal
      cortisol were measured using an enzyme-linked immunoassay. Housing condition had
      no effect on serum or fecal cortisol, but socially housed hamsters displayed
      modest thymus gland involution. Socially housed females weighed more than did any
      other group, and socially housed females and males had more fat than did socially
      isolated hamsters. No wounding or tissue damage occurred in grouped hamsters.
      Overall, these data suggest that Syrian hamsters tolerate both stable social
      housing and social isolation in the laboratory although social housing is
      associated with some alteration in stress-related and bioenergetic measures.

PMID- 28511868
TI  - Tunnel malpositions in anterior cruciate ligament risk cartilaginous changes and
      bucket-handle meniscal tear: Arthroscopic survey in both primary and revision
      surgery.
AB  - OBJECTIVES: There are not many chances to arthroscopically reassess how graft
      tunnel malpositions in primary anterior cruciate ligament reconstruction (ACLR)
      associate with intra-articular degeneration in revision ACLR. This study was
      aimed to evaluate whether radiographic tunnel position in primary ACLR affect
      cartilaginous changes and bucket-handle meniscus tears in revision ACLR. METHODS:
      Thirty-five patients who underwent revision ACLR were recruited; their primary
      surgeries were single-bundle reconstructions. Tunnel positions were evaluated
      using the plain radiographs after primary surgery. The sagittal tunnel positions
      of the femur (FP) and tibia (TP) were determined on the lateral view. The
      articular cartilage was evaluated arthroscopically at primary and revision
      surgery using the International Cartilage Repair Society (ICRS) score. A
      progression of two grades was considered as cartilaginous changes. Meniscal tears
      were evaluated with an arthroscopic probe. Logistic regression analysis was
      conducted using the prevalence of cartilaginous changes or bucket-handle meniscus
      tears as the dependent variable; tunnel parameters were used as the independent
      variables. RESULTS: Seven patients (20.0%) had cartilaginous changes and nine
      patients (25.7%) had bucket-handle tears in the medial meniscus. In logistic
      regression analysis, %FP [odds ratio (OR): 1.212; P = 0.007] and the cut-off of
      60% in the FP (OR: 22.000; P = 0.008) were correlated with cartilaginous changes.
      %TP (OR: 1.126; P = 0.036) was correlated with the prevalence of bucket-handle
      meniscus tears. CONCLUSIONS: Anterior femoral tunnel malposition in the femur was
      associated with the cartilaginous changes, and posterior tibial tunnel
      malposition with the development of bucket-handle meniscus tears.

PMID- 28511869
TI  - Markers of the p53 pathway further refine molecular profiling in high-risk
      endometrial cancer: A TransPORTEC initiative.
AB  - BACKGROUND: The morphological classification of high-risk endometrial cancer is
      of limited prognostic value. Recent attempts to stratify tumours according to
      molecular signatures have shown considerable promise. Here we attempted to
      further refine molecular classifications using markers of the p53 pathway.
      METHODS: We analysed the expression of p53 as well as three downstream markers of
      the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a
      series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype)
      with high-risk features (such as high tumour grade and deep myometrial invasion)
      and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data
      were used to analyse TP63 mutations and copy-number alterations using cBioPortal.
      TP53 was silenced in two endometrial cancer cell lines to study its effect on p21
      and p63. RESULTS: About half of the tumours showed a p53 mutant phenotype and
      there was a strong negative correlation with p21 expression. Being marker
      positive for pp63 or mdm2 was associated with a significantly increased
      likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04
      9.39), respectively]. These findings were seen in both p53 wildtype and p53
      mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63
      alteration. Upon silencing of TP53, p21 expression was decreased in one cell
      line, but no effects on p63 were observed. CONCLUSION: Markers of the p53 pathway
      improve stratification of endometrial cancers and provide novel insights into the
      role of this pathway in the disease.

PMID- 28511870
TI  - ATP-sensitive K+ channels maintain resting membrane potential in interstitial
      cells of Cajal from the mouse colon.
AB  - To investigate the role of ATP-sensitive K+(KATP) channels on pacemaker activity
      in interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and
      intracellular Ca2+([Ca2+]i) imaging were performed in cultured colonic ICC.
      Pinacidil (a K+ channel opener) hyperpolarized the membrane and inhibited the
      generation of pacemaker potential, and this effect was reversed by glibenclamide
      (a KATP channel blocker). RT-PCR showed that Kir 6.1 and SUR2B were expressed in
      Ano-1 positive colonic ICC. Glibenclamide depolarized the membrane and increased
      pacemaker potential frequency. However, 5-hydroxydecanoic acid (a mitochondrial
      KATP channel blocker) had no effects on pacemaker potentials. Phorbol 12
      myristate 13-acetate (PMA; a protein kinase C activator) blocked the pinacidil
      induced effects, and PMA alone depolarized the membrane and increased pacemaker
      potential frequency. Cell-permeable 8-bromo-cyclic AMP also increased pacemaker
      potential frequency. Recordings of spontaneous intracellular Ca2+([Ca2+]i)
      oscillations showed that glibenclamide increased the frequency of [Ca2+]i
      oscillations. In small intestinal ICC, glibenclamide alone did not alter the
      generation of pacemaker potentials, and Kir 6.2 and SUR2B were expressed in Ano-1
      positive ICC. Therefore, KATP channels in colonic ICC are activated in resting
      state and play an important role in maintaining resting membrane potential.

PMID- 28511871
TI  - Effect of distigmine on the contractile response of guinea pig urinary bladder to
      electrical field stimulation.
AB  - Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase
      (ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia
      gravis, distigmine is also indicated for detrusor underactivity in Japan.
      According to the pharmacological classification of distigmine, its therapeutic
      effect against detrusor underactivity appears to be produced by enhanced urinary
      bladder smooth muscle (UBSM) contractility due to an increased concentration of
      acetylcholine between parasympathetic nerve endings and UBSM cells. However, ATP
      as well as acetylcholine is also released from parasympathetic nerve endings that
      dominate UBSM. The present study was thus carried out to investigate the
      potentiating effects of distigmine on the two UBSM contractile components in
      response to parasympathetic nerve stimulation induced by electrical field
      stimulation (EFS). In isolated guinea pig UBSM tissues, EFS (1-16Hz) produced
      tetrodotoxin-sensitive, frequency-dependent contractions. The contractile
      responses to EFS were largely diminished by atropine (10-6M), and the remaining
      contractile components in the presence of atropine were virtually abolished by
      alpha,beta-methylene adenosine triphosphate (alpha,beta-mATP) (10-4M). Distigmine
      (10-6M) significantly potentiated EFS-induced contractile components generated in
      the presence of alpha,beta-mATP (10-4M), but did not potentiate EFS-induced
      contractile components generated in the presence of atropine (10-6M). These
      findings clearly indicate that distigmine strongly potentiates UBSM contraction
      selectively induced by parasympathetic nerve-derived acetylcholine, suggesting a
      potential mechanism by which distigmine restores detrusor underactivity.

PMID- 28511872
TI  - Impairment of tear film and the ocular surface in patients with facial burns.
AB  - AIM: The aim of this study is to investigate the factors affecting tear film and
      ocular surface in patients with facial burns. METHODS: A total of 273 patients
      with facial burns, treated at Hallym University Hangang Sacred Heart Hospital
      from November 2012 to July 2015, were included. Tear break-up time (TBUT),
      Schirmer's tear secretion test, fluorescein staining score (FSS), ocular surface
      disease index (OSDI), and visual analogue pain score (VAS) were compared
      according to burned surface area, burn site, burn cause, time since burn injury,
      or lid abnormality. RESULTS: Mean age was 48.66+/-14.46years (range: 18-85). Tear
      film stability was not different according to burn area, burn site, or burn
      cause. Facial burn patients with lid abnormalities had shorter TBUT and higher
      OSDI scores compared to no lid abnormality (p<0.001 and 0.015, independent t
      test). There was no difference in TBUT and tear secretion according to area,
      site, or cause of burn. FSS was different according to the area of burn (p=0.007,
      ANOVA). OSDI and VAS was higher in the patients with an electrical burn compared
      to thermal burn (p=0.003 and 0.024, ANOVA). CONCLUSIONS: Facial burn patients
      with lid abnormalities had tear film instability and ocular discomforts.
      Aggressive treatment may be of benefit in facial burn patients with lid
      involvement. Electrical burn caused more severe pain compared to thermal burn.
      Attention should be paid to pain control in patients with electrical burns.

PMID- 28511873
TI  - Misdiagnosis of vertebral fractures on local radiographic readings of the
      multicentre POINT (Prevalence of Osteoporosis in INTernal medicine) study.
AB  - BACKGROUND: Osteoporotic vertebral fractures (VFs) are often misdiagnosed because
      asymptomatic and occurring in the absence of specific trauma. Further, diagnostic
      assessment of VFs may be suboptimal. AIM OF THE STUDY: To assess the misdiagnosis
      of vertebral fractures on local radiographic readings in the cohort of patients
      enrolled in the POINT study. METHODS: We enrolled hospitalised patients, admitted
      for any cause to the Internal Medicine Units of 37 hospitals participating to the
      cross-sectional previously published POINT study. The assessment of VFs was
      performed both by local radiologists and by two expert skeletal radiologists, by
      using semiquantitative method (SQ). To better evaluate mild vertebral
      deformities, the two central radiologists also used the algorithm-based
      qualitative assessment (ABQ). RESULTS: The radiographs of 661 patients (401
      females; mean age 75.8+/-8.0) were evaluated. The inter-reader percent agreement
      between two central expert radiologists per-vertebra assessment was excellent
      (99.78%; k=0.984; 95% CI, 0.977-0.991). Central reading identified 318/661
      (48.1%) patients with at least one VF. Local and central readings agreed in
      502/661 (75.9%) patients, resulting in a fair reproducibility (k=0.52; 95%
      confidence interval 0.44-0.59). Diagnostic performance parameters of local
      readings were: sensitivity 76.1%; specificity 75.8%; PPV 74.46%; NPV 77.38%). By
      examining 9254 vertebrae, central and local readers diagnosed 665 (7.2%) and 562
      (6.1%) VFs respectively. Misdiagnosis (102 false positives and 205 false
      negatives) mainly occurred for mild VFs. Local readings identified correctly 460
      out 665 VFs diagnosed by central readings, resulting in sensitivity of 69.2% and
      PPV of 81.8%. CONCLUSIONS: Following a standardized protocol of acquisition
      techniques and of interpretation criteria, an excellent agreement between local
      and central readings for moderate and severe vertebral fractures resulted.
      However a significant amount of mild vertebral fractures, that are the most of
      VFs, were misdiagnosed by local radiologists. In order to improve VFs assessment,
      the radiologists should be trained and sensitized in relation to the relevant
      clinical significance of osteoporotic VFs identification.

PMID- 28511875
TI  - Visible light-switched cytosol release of siRNA by amphiphilic fullerene
      derivative to enhance RNAi efficacy in vitro and in vivo.
AB  - : Cationic macromolecules are attractive for use as small interfering RNA (siRNA)
      carriers due to their performance in non-immunological reactions, customization
      during synthesis, and low costs compared to viral carriers. However, their low
      transfection efficiency substantially hinders their application in both clinical
      practices and academic research, which is mostly attributable to the low capacity
      of siRNA/cationic macromolecule complexes to escape lysosomes. To address this
      challenge, we designed an amphiphilic fullerene derivative (C60-Dex-NH2) for
      efficient and controllable siRNA delivery. To synthesize C60-Dex-NH2, terminally
      aminated dextran was conjugated to C60. The conjugate was further cationized by
      covalently introducing ethylenediamine to the dextran. The physicochemical
      characteristics of C60-Dex-NH2 was examined with elemental analyses, gel
      permeation chromatography, solid-state nuclear magnetic resonance (13C, HPDEC),
      agarose gel electrophoresis, and dynamic light scattering. The cytotoxicity,
      cellular uptake, intracellular distribution, and in vitro RNA interference (RNAi)
      of siRNA/C60-Dex-NH2 complex was evaluated in the human breast cancer cell line
      MDA-MB-231. The RNAi efficiencies mediated by C60-Dex-NH2in vivo was evaluated in
      subcutaneous tumor-bearing mice. The results showed that C60-Dex-NH2 has a
      specific amphiphilic skeleton and could form micelle-like aggregate structures in
      water, which could prevent siRNA from destroying by reactive oxygen species
      (ROS). When exposed to visible light, C60-Dex-NH2 could trigger controllable ROS
      generation which could destroy the lysosome membrane, promote the lysosomal
      escape, and enhance the gene silencing efficiency of siRNA in vitro and in vivo.
      The gene silencing efficiency could reach a maximum of 53% in the MDA-MB-231-EGFP
      cells and 69% in the 4T1-GFP-Luc2 tumor-bearing mice. STATEMENT OF SIGNIFICANCE:
      We designed a novel photosensitive amphiphilic carrier (C60-Dex-NH2) for
      efficient and controllable siRNA delivery, which can be used in gene therapy. We
      showed that C60-Dex-NH2 could destroy lysosome membrane via controllable
      generation of ROS when exposed to light, which can help siRNA to escape from
      lysosome before degradation. This can enhance the gene silencing efficiency
      significantly and provides a useful way to regulate RNAi efficiency by light. One
      advantage for C60-Dex-NH2 system is C60 has broad absorbance spectrum and can be
      activated by weak visible light; Furthermore, C60-Dex-NH2 has a specific
      amphiphilic structure, which may prevent siRNA from degrading and allows C60-Dex
      NH2 to embed into the lipid membrane of lysosome to improve the ROS induced
      lysosomal disturbance after internalization.

PMID- 28511874
TI  - Photothermal and photodynamic activity of polymeric nanoparticles based on alpha
      tocopheryl succinate-RAFT block copolymers conjugated to IR-780.
AB  - : The aim of this work was the generation of a multifunctional nanopolymeric
      system that incorporates IR-780 dye, a near-infrared (NIR) imaging probe that
      exhibits photothermal and photodynamic properties; and a derivate of alpha
      tocopheryl succinate (alpha-TOS), a mitochondria-targeted anticancer compound. IR
      780 was conjugated to the hydrophilic segment of copolymer PEG-b-polyMTOS, based
      on poly(ethylene glycol) (PEG) and a methacrylic derivative of alpha-tocopheryl
      succinate (MTOS), to generate IR-NP, self-assembled nanoparticles (NPs) in
      aqueous media which exhibit a hydrophilic shell and a hydrophobic core. During
      assembly, the hydrophobic core of IR-NP could encapsulate additional IR-780 to
      generate derived subspecies carrying different amount of probe (IR-NP-eIR).
      Evaluation of photo-inducible properties of IR-NP and IR-NP-eIR were thoroughly
      assessed in vitro. Developed nanotheranostic particles showed distinct
      fluorescence and photothermal behavior after excitation by a laser light emitting
      at 808nm. Treatment of MDA-MB-453 cells with IR-NP or IR-NP-eIR resulted in an
      efficient internalization of the IR-780 dye, while subsequent NIR-laser
      irradiation led to a severe decrease in cell viability. Photocytoxicity conducted
      by IR-NP, which could not be attributed to the generation of lethal hyperthermia,
      responded to an increase in the levels of intracellular reactive oxygen species
      (ROS). Therefore, the fluorescence imaging and inducible phototoxicity
      capabilities of NPs derived from IR-780-PEG-b-polyMTOS copolymer confer high
      value to these nanotheranostics tools in clinical cancer research. STATEMENT OF
      SIGNIFICANCE: Multifunctional polymeric nanoparticles (NPs) that combine imaging
      and therapeutic properties are highly valuable in cancer treatment. In this paper
      we describe the development of NPs that are fluorescent in the near-infrared
      (NIR). This is important for their visualization in living tissues that present
      low absorption and low autofluorescence in this wavelength region (between 700
      and 1000nm). Moreover, NPs present photothermal and photodynamic properties when
      NIR irradiated: the NPs produce an efficient increment of temperature and
      increase the intracellular reactive oxygen species (ROS) when laser irradiated at
      808nm. These tuneable photoinduced properties make the NPs highly cytotoxic after
      NIR irradiation and provide a new tool for highly precise cancer treatment.

PMID- 28511876
TI  - Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for
      miR-34a delivery.
AB  - : Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM)
      through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR
      34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient
      cellular uptake of miR-34a in a CD44-dependent endocytosis way and further
      facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a
      delivery, obvious inhibition of cell proliferation could be detected which was
      attributed to the enhancement of cell apoptosis and cell cycle arrest, and
      meanwhile the cell migration and invasion has been observed to be inhibited.
      Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice
      bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit
      the tumor growth and induce the tumor apoptosis owing to the enhanced
      accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be
      used as a tumor-targeted oligonucleotide carrier for achieving tumor gene
      therapy. STATEMENT OF SIGNIFICANCE: The cationic dendrimer PAMAM was modified by
      chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted
      carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an
      efficient cellular uptake and intracellular transfection of miR-34a in a CD44
      dependent endocytosis manner. The miR-34a delivery could execute the anti
      proliferation activity by simultaneously inducing cell apoptosis and cell cycle
      arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic
      delivery of miR-34a showed significant inhibition of tumor growth and induction
      of tumor apoptosis using a mice model of subcutaneously implanted tumors.

PMID- 28511879
TI  - [Pneumopericardium in a patient with lung carcinoma].

PMID- 28511878
TI  - Epidemiological multicentre study on the education provided to patients with type
      2 diabetes mellitus in the Spanish Health Care System. The Forma2 study.
AB  - PURPOSE: The purpose of the present study was to characterize the education that
      patients with type 2 diabetes mellitus receive, and to identify differences as
      regards the presence of insulin therapy or not. METHODS: This crossover,
      multicentre and descriptive study involved 1066 Spanish physicians who completed
      a questionnaire on Internet. RESULTS: The physicians that responded had a mean of
      26.0 years of experience in healthcare, and mainly worked in a walk-in clinic in
      an urban area. Physicians rated the level of patient knowledge about their
      disease on a 5.0 point-scale. Fifty percent of them indicated that they spent
      between 15 and 30min in educating patients at the time of diagnosis. Previous
      control with HbA1c>9%, presence of microvascular complications, and a low socio
      cultural level, were factors associated with spending more time in education.
      CONCLUSION: This is the first study designed to evaluate the education provided
      to patients with type 2 diabetes mellitus from Spain. The time spent and the
      individualization of the education are important factors associated with better
      long-term control of the disease, and thus with the effectiveness of the clinical
      management.

PMID- 28511877
TI  - [Inflammatory injury on the chin].

PMID- 28511880
TI  - [The tired adolescent: Evaluation and management in the family practice].
AB  - The narrative review is used as a methodological tool for the presentation of
      this article. A search was made in the PubMed, Elsevier, Ebsco, and Medline
      databases using temporal limits (publications from 2005 to 2016), in the Spanish,
      English, and Portuguese language, and by the type of persons analysed in the
      study (adolescents), along with the keywords in English: Adolescent/teen,
      tiredness, fatigue, sleepiness, drowsiness. A total of 33 articles of relevance
      were obtained for the diagnostic and therapeutic approach of the tired adolescent
      in Primary Care. It was found that the main cause of excessive daytime sleepiness
      and drowsiness in adolescents is insufficient or inadequate sleep. For this
      reason, a sleep assessment should be a routine component of the clinical
      evaluation of adolescents, and as the initial approach to dismiss secondary
      causes.

PMID- 28511881
TI  - [What medication should be prescribed to a patient with coeliac disease?]
AB  - Coeliac disease is a permanent intolerance to gluten proteins from wheat, rye,
      barley and triticale. Although strict adherence is complicated, the only
      effective treatment is a gluten-free diet throughout life. Some drugs contain
      starch as an excipient, and there is a risk related to the gluten content, which
      must be avoided in these patients. Current legislation requires the analysis of
      the protein content of wheat starch, or the absence of starches from another
      source where rice, maize, or potato starches are used as excipients. But, it does
      not specify that reference should be made to traces of gluten that are residues
      of the process of production of the active ingredient. As regards the case
      described, there needs to be awareness of the importance of adequately informing
      patients and reviewing/updating current legislation to ensure the safe use of
      drugs.

PMID- 28511882
TI  - [Warning of a resistant psoriasis; looking beyond the usual].

PMID- 28511884
TI  - The Impact of Quality Variations on Patients Undergoing Surgery for Renal Cell
      Carcinoma: A National Cancer Database Study.
AB  - BACKGROUND: Despite efforts to define metrics assessing hospital-level quality
      for renal cell carcinoma (RCC) surgical care there remains a paucity of real
      world data validating their ability to benchmark performance. Consequently,
      whether poor performance on hospital-level quality indicators is associated with
      inferior patient outcomes remains unknown. OBJECTIVES: To determine hospital
      level variations in RCC surgical quality after adjusting for differences in
      patient- and tumor-specific factors. Further, to determine associations between
      hospital-level quality performance and surgical volume, academic affiliation, and
      patient mortality. DESIGN, SETTING, AND PARTICIPANTS: RCC patients undergoing
      surgery in the USA and Puerto Rico (2004-2014) were identified from the National
      Cancer Database. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Hospital-level
      quality of care was assessed according to disease-specific process and outcome
      quality indicators. Case-mix adjusted hospital benchmarking was performed using
      indirect standardization methodology and multivariable regression models. A
      composite measure of quality, the Renal Cancer Quality Score (RC-QS), was
      subsequently derived and associations between RC-QS and surgical volume, academic
      affiliation, and patient mortality were determined. RESULTS AND LIMITATIONS: Over
      1100 hospitals were benchmarked for quality, with 10-31% identified as providing
      poor care for a given quality indicator. Lower RC-QS hospitals had smaller
      referral volumes and were less academic compared with higher RC-QS hospitals
      (p<0.001). Higher RC-QS was independently associated with lower 30-d, 90-d, and
      overall mortality (adjusted odds ratio [confidence interval]: 0.92 [0.90-0.95],
      odds ratio: 0.94 [0.91-0.96], hazard ratio: 0.97 [0.96-0.98] per unit increase,
      respectively). These data are retrospective and it is unknown whether improvement
      in the RC-QS improves outcomes. CONCLUSIONS: Widespread hospital-level variations
      in RCC surgical quality exist, as captured by the RC-QS. Superior quality is
      associated with improved patient outcomes, including mortality benefit. The RC-QS
      serves as a benchmarking tool for RCC quality that can provide audit level
      feedback to hospitals and policymakers for quality improvement. PATIENT SUMMARY:
      We benchmarked hospital performance across quality indicators for kidney cancer
      surgical care. Overall, large variations in quality exist, with high volume
      academic hospitals demonstrating superior performance and improved patient
      survival. These data can inform hospitals and policymakers for quality
      improvement initiatives.

PMID- 28511885
TI  - Salivary changes in type 2 diabetic patients.
AB  - OBJECTIVE: this study was conducted to determine the effect of type 2 diabetes
      mellitus on salivary secretion of glucose, amylase and immunoglobulin A levels
      and also to fined out if saliva could be used as anon invasive method to monitor
      glycaemic control in type 2 diabbetes. This study was conducted on 40 human
      subjectes, They were 20 males and 20 females, their ages ranged from 35 years to
      64 years,and they were divided into two groups, the first one is the patient
      group which contains 20 diabetic paient. (10 males and 10 females,aged between 38
      years to 64 years). the second one is the control group which contains 20 healthy
      adult (10 males and 10 females,aged between 35 years to 60 years) they were age
      and sex matched. All studied group were subjected to clinical and laboratory
      investigation which includes post prandial blood glucose, HA1C, salivary glucose,
      salivary amylase, and salivary immunoglobulin A. RESULTS: there was a highly
      significant increase in the level of post prandial blood glucose, HBA1C; Salivary
      glucose, Salivary amylase & Salivary immunoglobulin A in diabetic group compared
      with control group and There was a significant positive correlation between post
      prandial blood glucose and salivary glucose in diabetic group. CONCLUSIONS: These
      results suggest that diabetes influences the composition of saliva and that
      saliva can be used as less painful,non invasive biomarker for monitoring the
      blood glucose concentration in the patients with diabetes mellitus.

PMID- 28511883
TI  - A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation
      Underpin Aggression of Intraductal and Cribriform Subpathologies.
AB  - BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA)
      represent unfavorable subpathologies in localized prostate cancer. We recently
      showed that IDC shares a clonal ancestry with the adjacent glandular
      adenocarcinoma. OBJECTIVE: We investigated for the co-occurrence of "aggression"
      factors, genomic instability and hypoxia, and performed gene expression profiling
      of these tumors. DESIGN, SETTING, AND PARTICIPANTS: A total of 1325 men were
      treated for localized prostate cancer from four academic institutions (University
      Health Network, CHU de Quebec-Universite Laval, Memorial Sloan Kettering Cancer
      Center [MSKCC], and Erasmus Medical Center). Pathological specimens were
      centrally reviewed. Gene copy number and expression, and intraprostatic
      oxygenation were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: IDC/CA
      was separately assessed for biochemical relapse risk in the Canadian and MSKCC
      cohorts. Both cohorts were pooled for analyses on metastasis. RESULTS AND
      LIMITATION: Presence of IDC/CA independently predicted for increased risks of
      biochemical relapse (HRCanadian 2.17, p<0.001; HRMSKCC 2.32, p=0.0035) and
      metastasis (HRpooled 3.31, p<0.001). IDC/CA+ cancers were associated with an
      increased percentage of genome alteration (PGA [median] 7.2 vs 3.0, p<0.001), and
      hypoxia (64.0% vs 45.5%, p=0.17). Combinatorial genomic-pathological indices
      offered the strongest discrimination for metastasis (C-index 0.805
      [clinical+IDC/CA+PGA] vs 0.786 [clinical+IDC/CA] vs 0.761 [clinical]). Profiling
      of mRNA abundance revealed that long noncoding RNA, SChLAP1, was the only gene
      expressed at >3-fold higher (p<0.0001) in IDC/CA+ than in IDC/CA- tumors,
      independently corroborated by increased SChLAP1 RNA in situ hybridization signal.
      Optimal treatment intensification for IDC/CA+ prostate cancer requires
      prospective testing. CONCLUSIONS: The poor outcome associated with IDC and CA
      subpathologies is associated with a constellation of genomic instability, SChLAP1
      expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer,
      "nimbosus" (gathering of stormy clouds, Latin), which manifests as increased
      metastatic capacity and lethality. PATIENT SUMMARY: A constellation of
      unfavorable molecular characteristics co-occur with intraductal and cribriform
      subpathologies in prostate cancer. Modern imaging for surveillance and treatment
      intensification trials should be considered in this adverse subgroup.

PMID- 28511887
TI  - Antioxidant polyphenols in cancer treatment: Friend, foe or foil?
AB  - Cancer prevention can be probably obtained with easier, faster and less financial
      strains by pursuing educational programs aimed to induce changes in lifestyle,
      starting from dietary habits. In the past decades, observational and case-control
      studies tried to establish a functional relationship between cancer mortality and
      morbidity and diet. The field becomes even more intricate when scientists
      investigated which dietary components are responsible for the putative,
      protective effects of fruits and vegetables against cancer. A relevant part of
      the literature focused on the positive role of "antioxidant" compounds in foods,
      including polyphenols. The present review critically evaluate clinical and pre
      clinical studies based on polyphenol administration, which contributed to support
      the concept, deeply rooted in the general population, that antioxidant
      polyphenols can fight cancer. The controversial and contradictory issues related
      to the pros and cons on the use of polyphenols against cancer reflect the
      confounding assumption that cancer treatment and cancer prevention may overlap.
      We conclude that a clear cut must be done between these two concepts and that the
      experimental approaches to investigate one or the other should be significantly
      different, starting from adequate and specifically selected cellular models.

PMID- 28511889
TI  - Severely infected pneumoceles of the frontal sinus in patients with mental
      retardation and brain atrophy treated by endoscopic sinus surgery.
AB  - We herein present three cases of abnormally expanded frontal sinuses
      (pneumoceles) with severe infection in patients with mental retardation and brain
      atrophy. Two patients previously underwent laryngotracheal separation surgery,
      and bacteriological examinations of purulent nasal discharge revealed infections
      caused by drug-resistant bacteria such as Pseudomonas aeruginosa and
      Acinetobacter baumannii. As conservative medical treatments were ineffective, all
      three patients were treated by computed tomography-guided endoscopic sinus
      surgery. This navigation system is useful for safer surgery in the area of
      anatomic deformity. The clinical findings, possible etiologies and surgical
      treatment of these cases are discussed.

PMID- 28511888
TI  - Simple visual review of pre- to post-operative renal ultrasound images predicts
      pyeloplasty success equally as well as geometric measurements: A blinded
      comparison with a gold standard.
AB  - BACKGROUND: MAG3 diuretic renal scan remains the gold standard for determination
      of improvement in renal drainage following pyeloplasty for ureteropelvic junction
      obstruction. We hypothesized that (i) a change in geometric measurements between
      pre-operative and post-operative renal ultrasound (RUS) images and (ii) blinded
      simple visual review of images both would predict pyeloplasty success. OBJECTIVE:
      To determine if simple visual review and/or novel geometric measurement of renal
      ultrasounds can detect pyeloplasty failure. STUDY DESIGN: This study was a
      retrospective, blinded comparison with a gold standard. Included were children
      aged <=18 years undergoing pyeloplasty at our institution from 2009 to 2015. For
      each kidney, representative pre-operative and post-operative RUS images were
      chosen. Our standard for pyeloplasty success was improved drainage curve on MAG3
      and lack of additional surgery. Measurements for collecting system circularity,
      roundness, and renal parenchymal to collecting system area ratio (RPCSR) were
      obtained by three raters (Figure), who were blinded to the outcome of the
      pyeloplasty. Changes in geometric measurements were analyzed as a diagnostic test
      for MAG3-defined pyeloplasty success using ROC curve analysis. In addition, six
      reviewers blinded to pyeloplasty success reviewed pre-operative and post
      operative images visually for improved hydronephrosis and categorized pyeloplasty
      as success or failure based on simple visual review of RUS. RESULTS: Fifty-three
      repaired renal units were identified (50 children). There were five pyeloplasty
      failures, four of which underwent revision or nephrectomy. While all geometric
      measurements could discriminate pyeloplasty failure and success, the geometric
      measurements that discriminated best between pyeloplasty failure and success were
      change in collecting system roundness and change in RPCSR. Consensus opinion
      among six blinded reviewers using simple visual review had a sensitivity of 94%
      and PPV of 100% with respect to identifying pyeloplasty success (AUC 0.97 (95% CI
      0.93-1.0)). This was not significantly different from AUC for change in roundness
      (p = 0.09) or change in RPCSR (p = 0.1). DISCUSSION: Change in collecting system
      roundness and change in RPCSR were the most accurate geometric measurements in
      predicting pyeloplasty success. Simple visual review of ultrasound images for
      pyeloplasty success performed as well or better than geometric measurements.
      However, geometric measurements remain useful as a research tool or to
      communicate findings between clinicians. CONCLUSIONS: Complex geometric
      measurements of hydronephrosis or post-operative MAG3 scans are not needed if
      hydronephrosis is visually significantly improved, as simple visual review is
      highly sensitive for detecting pyeloplasty failure.

PMID- 28511886
TI  - Numtogenesis as a mechanism for development of cancer.
AB  - Transfer of genetic material from cytoplasmic organelles to the nucleus, an
      ongoing process, has implications in evolution, aging, and human pathologies such
      as cancer. The transferred mitochondrial DNA (mtDNA) fragments in the nuclear
      genome are called nuclear mtDNA or NUMTs. We have named the process numtogenesis,
      defining the term as the transfer of mtDNA into the nuclear genome, or, less
      specifically, the transfer of mitochondria or mitochondrial components into the
      nucleus. There is increasing evidence of the involvement of NUMTs in human
      biology and pathology. Although information pertaining to NUMTs and numtogenesis
      is sparse, the role of this aspect of mitochondrial biology to human cancers is
      apparent. In this review, we present available knowledge about the origin and
      mechanisms of numtogenesis, with special emphasis on the role of NUMTs in human
      malignancies. We describe studies undertaken in our laboratory and in others and
      discuss the influence of NUMTs in tumor initiation and progression and in
      survival of cancer patients. We describe suppressors of numtogenesis and
      evolutionary conserved mechanisms underlying numtogenesis in cancer. An
      understanding the emerging field of numtogenesis should allow comprehension of
      this process in various malignancies and other diseases and, more generally, in
      human health.

PMID- 28511890
TI  - Intratympanic steroid delivery by an indwelling catheter in refractory severe
      sudden sensorineural hearing loss.
AB  - OBJECTIVE: Many studies over the last decade showed favorable outcomes with
      intratympanic (IT) steroid treatment, alone as salvage treatment or in
      combination with conventional systemic therapy (ST). However, in severe to
      profound sensorineural hearing loss resistant to ST, the optimal infusion mode,
      the type and concentration of the solution, the preferable drug, its total
      amount, and the duration and fractionation of the treatment are still debated.
      Aim of the study was to investigate the feasibility and the outcomes of a direct
      and constant IT delivery of dexamethasone (DEX) by means of a new indwelling
      catheter. METHODS: A prospective case-control study in a tertiary referral
      university hospital. Ninety-nine subjects treated with ST only and 28 with
      additional IT DEX have been included in the study. A 4 Fr catheter inserted in a
      sub-annular fashion with a minimal postero-inferior tympanotomy through and
      endocanalar approach under local anesthesia. DEX 4mg/ml delivered daily, up to 7
      days. Daily bone and air-conducted pure tone and speech audiometry were performed
      with a follow-up at 1, 3, 6 months after treatment. RESULTS: Twenty-one out of 28
      patients (75%) refractory to ST gained on average 24.0dB+/-20.5dB HL after IT
      DEX, compared to 35.4% (average 6.7dB+/-16.6dB HL) of those receiving only
      medical ST (p<0.001). No significant side effects were noted. CONCLUSION: In
      severe to profound sudden deafness refractory to conventional ST, the daily
      perfusion of 4mg/ml DEX through an intratympanic catheter is an easy, well
      accepted procedure that enables patients to receive a drug in the middle ear in a
      repeatable or sustained form, with minimal discomfort and a partial rescue
      (67.86%) and a speech recognition gain of 39%.

PMID- 28511891
TI  - External pelvic and vaginal irradiation vs. vaginal irradiation alone as
      postoperative therapy in women with early stage uterine serous carcinoma: Results
      of a National Cancer Database analysis.
AB  - PURPOSE: Adjuvant treatment in early stage uterine serous carcinoma (USC) usually
      consists of chemotherapy with vaginal brachytherapy (VB), pelvic external beam
      radiation therapy (EBRT), or combination. We compared survival outcomes across
      these various radiation treatment modalities using the National Cancer Database.
      METHODS AND MATERIALS: The National Cancer Database was queried for adult females
      with histologically confirmed International Federation of Gynecology and
      Obstetrics 1988 Stage I-II USC diagnosed from 2003 to 2013 treated definitively
      with hysterectomy, adjuvant chemotherapy, and radiation therapy. chi2 tests were
      used to assess differences by radiation type (VB, pelvic EBRT, and EBRT + VB) and
      various clinical variables. Kaplan-Meier and log-rank test methods were used to
      evaluate survival outcomes. Risk factors related to overall survival were
      identified by univariate and multivariate analysis. RESULTS: We identified 1336
      patients with USC who met our inclusion criteria. Most patients were treated with
      VB (66%) compared with EBRT (21%) or combination EBRT + VB (13%). The proportion
      of patients who received EBRT (including EBRT + VB) was higher for those who did
      not have a lymph node dissection or with fewer dissected lymph nodes. Patients
      treated with VB alone had longer 5-year survival rates (84% [95% confidence
      interval: 80, 90]) than those treated with EBRT (75% [95% confidence interval:
      69, 80]) (p < 0.001). On multivariate analysis, the presence of lymphovascular
      space invasion (hazard ratio, 2.48; p < 0.001) and the absence of a lymph node
      dissection (hazard ratio, 2.24; p = 0.047) were independent predictors of overall
      survival. CONCLUSIONS: This large hospital-based study suggests that VB alone may
      be sufficient for adjuvant radiation treatment in women with USC treated with
      adjuvant chemotherapy and who underwent an adequate surgical staging.

PMID- 28511892
TI  - Occurrence and biosynthesis of carotenoids in phytoplankton.
AB  - Naturally occurring carotenoids are important sources of antioxidants, anti
      cancer compounds and anti-inflammatory agents and there is thus considerable
      market demand for their pharmaceutical applications. Carotenoids are widely
      distributed in marine and freshwater organisms including microalgae,
      phytoplankton, crustaceans and fish, as well as in terrestrial plants and birds.
      Recently, phytoplankton-derived carotenoids have received much attention due to
      their abundance, rapid rate of biosynthesis and unique composition. The
      carotenoids that accumulate in particular phytoplankton phyla are synthesized by
      specific enzymes and play unique physiological roles. This review focuses on
      studies related to the occurrence of carotenoids in different phytoplankton phyla
      and the molecular aspects of their biosynthesis. Recent biotechnological advances
      in the isolation and characterization of some representative carotenoid synthases
      in phytoplankton are also discussed.

PMID- 28511893
TI  - Assessment of the effectiveness of attenuation of Pb aprons by using TLD
      dosimetry and Monte Carlo calculations.
AB  - We developed an experimental set-up by using a continuous emission X-ray (Pantak
      DXT-3000) and three types of Pb aprons, with thicknesses of 0.25, 0.5, and
      0.75mm, coated with Mylar fiber on their surface. Aprons were placed at a
      distance of 2.5m from the focus. Aluminum filtration was performed at the beam
      output to reproduce the qualities of narrow beams, N40 (Eeffective =33keV), N80
      (Eeffective =65keV), and N100 (Eeffective =83keV), according to the ISO standard
      4037 (1-3). Each apron was fixed with 10 thermoluminescent dosimeters (TLDs) over
      its surface, five dosimeters before and five dosimeters after irradiation with X
      rays. Dosimeter readings were noted, and the attenuation coefficients for each
      effective energy were calculated. To confirm the method of effective energy of
      ISO-4037 and evaluate the effectiveness of aprons according to the energy range
      required for different medical practices, a Monte Carlo simulation using GEANT4
      code was performed. Thus, the fluence and the absorbed dose in each of the
      dosimeters were determined, and then the coefficients of linear attenuation were
      calculated and compared with the experimental data and with those reported by the
      National Institute of Standards and Technology. Results were consistent between
      theoretical calculations and experimental measures. This work will serve to make
      assessments for other personalized radiation protectors made of Pb.

PMID- 28511894
TI  - Incorporating simulation into gynecologic surgical training.
AB  - Today's educational environment has made it more difficult to rely on the
      Halstedian model of "see one, do one, teach one" in gynecologic surgical
      training. There is decreased surgical volume, but an increased number of surgical
      modalities. Fortunately, surgical simulation has evolved to fill the educational
      void. Whether it is through skill generalization or skill transfer, surgical
      simulation has shifted learning from the operating room back to the classroom.
      This article explores the principles of surgical education and ways to introduce
      simulation as an adjunct to residency training. We review high- and low-fidelity
      surgical simulators, discuss the progression of surgical skills, and provide
      options for skills competency assessment. Time and money are major hurdles when
      designing a simulation curriculum, but low-fidelity models, intradepartmental
      cost sharing, and utilizing local experts for simulation proctoring can aid in
      developing a simulation program.

PMID- 28511896
TI  - [Changes in the prevalence of statin use in Germany - findings from national
      health interview and examination surveys 1997-1999 and 2008-2011].
AB  - BACKGROUND: Evidence-based guideline recommendations on lipid lowering drug
      treatment, in particular statin treatment, play an essential role in the
      management of dyslipidemias and in the prevention of cardiovascular disease
      events. In Germany, statutory health insurance data provide information on time
      trends in the prescription of lipid lowering drugs. However, population-based
      data regarding changes in user prevalence according to socio-demographic and
      health-related characteristics are lacking. Based on data from national health
      interview and examination surveys for adults in Germany 1997-1999 (GNHIES98) and
      2008-2010 (DEGS1), the present analysis aims to close this information gap with a
      particular focus on the use of statins. METHODS: The study population consisted
      of 7,099 participants (GNHIES98) and 7,091 participants (DEGS1) aged 18 to 79
      years at the time of the respective surveys. Primary data on medication use
      within 7 days prior to the survey were collected using standardized medication
      interviews and brown-bag drug review. Unique product identifiers on original drug
      containers were scanned and coded according to the latest version of the
      Anatomical Therapeutic Chemical (ATC) classification system. Medical history was
      obtained in computer-assisted personal interviews. A history of stroke or
      coronary heart disease (CHD) was assessed among persons aged 40 to 79 years only,
      and previous stroke or CHD were defined as cardiovascular disease. Obesity was
      defined as a body mass index (BMI) of >= 30kg/m2) based on calculation from
      standardized measures of body weight and height. Information on socio-demographic
      variables and type of health insurance was collected using standardized self
      administered questionnaires. In cross-sectional descriptive analyses we
      calculated the prevalence of statin use (ATC codes: C10AA, C10BA, C10BX) by
      survey as well as the changes between surveys stratified according to relevant
      preexisting diseases and other co-variables. The association between survey
      period and statin use was analyzed in multivariable binary logistic regression
      models among persons aged 40 to 79 years. All results were weighted and
      standardized for the population of 2010. RESULTS: Between the two survey periods
      1997-1999 and 2008-2011, the prevalence of statin use increased from 3.2 % to 8.8
      %. The increase was most pronounced for the age group 65 to 79 years (7.2 % vs.
      26.9 %) and among persons with relevant preexisting conditions, such as CHD (19.1
      % vs. 54.9 %), stroke (17.1 % vs. 50.1 %), diabetes mellitus (10.5 % vs. 33.2 %),
      and dyslipidemia (12.6 % vs. 27.8 %). Among persons aged 40 to 79 years, the
      prevalence of statin use significantly increased between the two surveys,
      independent of co-variables (Odds Ratio: 3.70; 95 % confidence interval [CI]:
      2.92 to 4.70). This applied to persons with cardiovascular disease (5.17; 3.50 to
      7.64) and without cardiovascular disease (2.76; 2.07 to 3.67). CONCLUSION: The
      increase in the prevalence of statin use in Germany between the two national
      health surveys (1997-1999 and 2008-2011) reflects the implementation of current
      guideline recommendations without evidence for inequalities according to gender,
      education, type of health insurance or region of residence. These population
      based data add to information on statin prescription obtained from statutory
      health insurance data. Limitations of survey-based information derive from
      potential misclassification and selection bias as well as large time gaps between
      the survey periods. Further studies are needed to examine why the observed
      prevalence of statin use among persons with cardiovascular morbidity lags behind
      current guideline recommendations for secondary cardiovascular prevention.

PMID- 28511897
TI  - Takotsubo in amyotrophic lateral sclerosis.

PMID- 28511898
TI  - Is the Takotsubo syndrome a brain-heart or multiorgan disorder?

PMID- 28511895
TI  - Diagnostic performance of Anyplex II MTB/MDR/XDR for detection of resistance to
      first and second line drugs in Mycobacterium tuberculosis.
AB  - PURPOSE: Genotypic methods have considerably improved the diagnosis of multidrug
      resistant (MDR) tuberculosis. One of these tests is Anyplex II MTB/MDR/XDR
      (Anyplex). Our aim was to evaluate the diagnostic performance of this multiplex
      PCR. METHODS: We conducted our study on 47 MDR tuberculosis and 14 pan
      susceptible strains. We evaluated the ability of Anyplex to detect resistance
      mutations in rpoB (rifampin [RIF]), katG and inhA (isoniazid [INH]), gyrA
      (fluoroquinolones [FLQ]), and rrs and eis (aminoglycosides [AMG]). We used the
      agar proportion method as gold standard. We also studied concordance with
      GenoType MTBDRplus (first line drugs) and MTBDRsl (second line drugs). DNA
      sequencing was applied to clarify discrepancies. RESULTS: All pan-susceptible
      strains were susceptible by Anyplex. Sensitivity and specificity of Anyplex for
      detection of resistance mutations were 97.9% and 100%, respectively, for RIF,
      91.5% and 100% for INH, 80% and 100% for FLQ, and 50% and 99.7% for AMG.
      Concordance with GenoType was perfect for RIF, INH, and FLQ (kappa score, k=1.0)
      and moderate for AMG (k=0.48). Sensitivity and specificity for detection of MDR
      tuberculosis were 89.4% and 100%, respectively. DNA sequencing of the
      phenotypically resistant strains considered as susceptible by Anyplex, confirmed
      no mutations in the corresponding genes. CONCLUSIONS: Anyplex is a reliable assay
      for the detection of MDR tuberculosis and shows excellent concordance with
      GenoType. Anyplex reduces the time to diagnosis of MDR tuberculosis strains, as
      it is recommended by current guidelines on control of tuberculosis.

PMID- 28511899
TI  - Signaling pathways to and from the hypophysial pars tuberalis, an important
      center for the control of seasonal rhythms.
AB  - Seasonal (circannual) rhythms play an important role for the control of body
      functions (reproduction, metabolism, immune responses) in nearly all living
      organisms. Also humans are affected by the seasons with regard to immune
      responses and mental functions, the seasonal affective disorder being one of the
      most prominent examples. The hypophysial pars tuberalis (PT), an important
      interface between the hypophysial pars distalis and neuroendocrine centers in the
      brain, plays an essential role in the regulation of seasonal functions and may
      even be the seat of the circannual clock. Photoperiodic signals provide a major
      input to the PT. While the perception of these signals involves extraocular
      photoreceptors in non-mammalian species (birds, fish), mammals perceive
      photoperiodic signals exclusively in the retina. A multisynaptic pathway connects
      the retina with the pineal organ where photoperiodic signals are translated into
      the neurohormone melatonin that is rhythmically produced night by night and
      encodes the length of the night. Melatonin controls the functional activity of
      the mammalian PT by acting upon MT1 melatonin receptors. The PT sends its output
      signals via retrograde and anterograde pathways. The retrograde pathway
      targetting the hypothalamus employs TSH as messenger and controls a local
      hypothalamic T3 system. As discovered in Japanese quail, TSH triggers molecular
      cascades mediating thyroid hormone conversion in the ependymal cell layer of the
      infundibular recess of the third ventricle. The local accumulation of T3 in the
      mediobasal hypothalamus (MBH) appears to activate the gonadal axis by affecting
      the neuro-glial interaction between GnRH terminals and tanycytes in the median
      eminence. This retrograde pathway is conserved in photoperiodic mammals (sheep
      and hamsters), and even in non-photoperiodic laboratory mice provided that they
      are capable to synthesize melatonin. The anterograde pathway is implicated in the
      control of prolactin secretion, targets cells in the PD and supposedly employs
      small molecules as signal substances collectively denominated as "tuberalins".
      Several "tuberalin" candidates have been proposed, such as tachykinins, the
      secretory protein TAFA and endocannabinoids (EC). The PT-intrinsic EC system was
      first demonstrated in Syrian hamsters and shown to respond to photoperiodic
      changes. Subsequently, the EC system was also demonstrated in the PT of mice,
      rats and humans. To date, 2-arachidonoylglycerol (2-AG) appears as the most
      important endocannabinoid from the PT. Likely targets for the EC are folliculo
      stellate cells that contain the CB1 receptor and appear to contact lactotroph
      cells. The CB1 receptor was also found on corticotroph cells which appear as a
      further target of the EC. Recently, the CB1 receptor was also localized to CRF
      containing nerve fibers running in the outer zone of the median eminence. This
      finding suggests that the EC system of the PT contributes not only to the
      anterograde, but also to the retrograde pathway. Taken together, the results
      support the concept that the PT transmits its signals via a "cocktail" of
      messenger molecules which operate also in other brain areas and systems rather
      than through PT-specific "tuberalins". Furthermore, they may attribute a novel
      function to the PT, namely the modulation of the stress response and immune
      functions.

PMID- 28511900
TI  - Predictive value of CT for first esophageal variceal bleeding in patients with
      cirrhosis: Score calibration and prediction.

PMID- 28511901
TI  - First haplosporidan parasite reported infecting a member of the Superfamily
      Pinnoidea (Pinna nobilis) during a mortality event in Alicante (Spain, Western
      Mediterranean).
AB  - Several stages of a haplosporidan parasite, including spores, were detected
      infecting three out of four specimens of the Pen Shell Pinna nobilis from the
      coast of Alicante (Western Mediterranean). A mortality event initiated few weeks
      before the sampling. The infection was systemic in the connective tissue, with
      free uni-nucleate stages and early plasmodia, whereas sporulation process took
      place in the digestive tubules disrupting them. Morphological details, by light
      and transmission electron microscopy, and PCR amplification confirmed that the
      parasite belongs to the haplosporidan group. Spores were pleomorphic, usually
      elongated ovoid, with round to elongated haplosporosomes-like in the sporoplasma.
      The operculum was situated in the apical zone of the wall, with an external lid,
      and the nucleus tended to be eccentric in the basal zone. Spore ornamentation was
      not observed. The single uninfected specimen appeared to be healthy. This is the
      first report of a haplosporidan parasite infecting a member of the Superfamily
      Pinnoidea and this is the first histopathological study of a mortality event in
      the endangered and protected P. nobilis.

PMID- 28511902
TI  - Adiposity as a full mediator of the influence of cardiorespiratory fitness and
      inflammation in schoolchildren: The FUPRECOL Study.
AB  - BACKGROUND AND AIMS: Studies in the paediatric population have shown inconsistent
      associations between cardiorespiratory fitness and inflammation independently of
      adiposity. The purpose of this study was (i) to analyse the combined association
      of cardiorespiratory fitness and adiposity with high-sensitivity C-reactive
      protein (hs-CRP), and (ii) to determine whether adiposity acts as a mediator on
      the association between cardiorespiratory fitness and hs-CRP in children and
      adolescents. METHODS AND RESULTS: This cross-sectional study included 935 (54.7%
      girls) healthy children and adolescents from Bogota, Colombia. The 20 m shuttle
      run test was used to estimate cardiorespiratory fitness. We assessed the
      following adiposity parameters: body mass index, waist circumference, and fat
      mass index and the sum of subscapular and triceps skinfold thickness. High
      sensitivity assays were used to obtain hs-CRP. Linear regression models were
      fitted for mediation analyses examined whether the association between
      cardiorespiratory fitness and hs-CRP was mediated by each of adiposity parameters
      according to Baron and Kenny procedures. Lower levels of hs-CRP were associated
      with the best schoolchildren profiles (high cardiorespiratory fitness + low
      adiposity) (p for trend <0.001 in the four adiposity parameters), compared with
      unfit and overweight (low cardiorespiratory fitness + high adiposity)
      counterparts. Linear regression models suggest a full mediation of adiposity on
      the association between cardiorespiratory fitness and hs-CRP levels. CONCLUSIONS:
      Our findings seem to emphasize the importance of obesity prevention in childhood,
      suggesting that having high levels of cardiorespiratory fitness may not
      counteract the negative consequences ascribed to adiposity on hs-CRP.

PMID- 28511903
TI  - Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL
      receptor 1-mediated endothelial dysfunction in comparison to lovastatin.
AB  - BACKGROUND AND AIMS: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to
      increased oxidative stress linked to endothelial dysfunction and atherosclerosis.
      The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering
      statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from
      plants of gender Berberis, has lipid-lowering and anti-inflammatory activity.
      However, its role in regulating LOX1-mediated signaling is still unknown. The aim
      of this study was to investigate the effect of BBR on oxLDL- and TNFalpha-induced
      endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to
      compare it with that of lovastatin (LOVA). METHODS AND RESULTS: Cytotoxicity was
      determined by lactate dehydrogenase assay. Antioxidant capacity was measured with
      chemiluminescent and fluorescent method and intracellular ROS levels through a
      fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and
      western blot, respectively. HUVECs exposure to oxLDL (30 MUg/ml) or TNFalpha (10
      ng/ml) for 24 h led to a significant increase in LOX1 expression, effect
      abrogated by BBR (5 MUM) and LOVA (5 MUM). BBR but not LOVA treatment abolished
      the TNFalpha-induced cytotoxicity and restored the activation of Akt signaling.
      In spite of a low direct antioxidant capacity, both compounds reduced
      intracellular ROS levels generated by treatment of TNFalpha but only BBR
      inhibited NOX2 expression, MAPK/Erk1/2 signaling and subsequent NF-kappaB target
      genes VCAM and ICAM expression, induced by TNFalpha. CONCLUSIONS: These findings
      demonstrated for the first time that BBR could prevent the oxLDL and TNFalpha -
      induced LOX1 expression and oxidative stress, key events that lead to NOX,
      MAPK/Erk1/2 and NF-kappaB activation linked to endothelial dysfunction. CHEMICAL
      COMPOUNDS STUDIED IN THIS ARTICLE: Berberine (PubChem CID: 2353); Lovastatin
      (PubChem CID: 53232).

PMID- 28511904
TI  - Analysis of the association of leptin and adiponectin concentrations with
      metabolic syndrome in children: Results from the IDEFICS study.
AB  - BACKGROUND AND AIMS: Adipokines may play a role in the pathogenesis of the
      metabolic syndrome (MetS) in children. We aimed to evaluate the association of
      leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS)
      in a subsample of the IDEFICS (Identification and prevention of Dietary- and
      lifestyle-induced health EFfects In Children and infantS) cohort. METHODS AND
      RESULTS: Leptin, adiponectin and MetS parameters were measured in a subsample of
      1253 children (3-9.9 years) participating to the IDEFICS study, grouped as: Non
      OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined
      using the sex- and age-specific cut-offs based on the distribution of MetS
      components in the IDEFICS cohort. The prevalence of the MetS among OW/Ob was
      24.8% and 27.1% in boys and girls respectively, whereas <=2% among Non-OW. OW/Ob
      had significantly higher leptin and L/A ratio as compared to Non-OW.
      Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob
      without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as
      compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD
      decrease in adiponectin z-score were significantly associated with higher risk of
      MetS. After adjustment for BMI or body fat mass (BFM) the association remained
      significant only for leptin. CONCLUSION: We showed that in European children,
      higher leptin concentration is associated with MetS, even after adjusting for BMI
      or BFM, confirming an early role of leptin in MetS, while the association of
      adiponectin with MetS seems be mediated by body fat in this age range.

PMID- 28511905
TI  - Hemorheological alterations in adults with prediabetes identified by hemoglobin
      A1c levels.
AB  - BACKGROUND AND AIMS: A link between increased blood viscosity and type 2 diabetes
      has been previously reported. Herein, we investigated the association of blood
      viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c)
      according to the new American Diabetes Association criteria, and subclinical
      atherosclerosis. METHODS AND RESULTS: The study cohort includes 1136 non-diabetic
      adults submitted to anthropometrical evaluation, an oral glucose tolerance test
      and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood
      viscosity was estimated using a validated formula based on hematocrit and total
      plasma proteins. After adjusting for age, and gender, individuals with HbA1c
      defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly
      higher values of hematocrit, and predicted blood viscosity as compared with
      controls. Increased levels of IMT were observed in subjects with HbA1c-defined
      prediabetes in comparison to controls. Predicted blood viscosity was positively
      correlated with age, waist circumference, blood pressure, cholesterol,
      triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load
      glucose levels, fasting insulin, IMT and inversely correlated with HDL and
      Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e.
      HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant
      correlation with predicted blood viscosity (beta = 0.054, P = 0.04) in a
      multivariate regression analysis model including multiple atherosclerosis risk
      factors. CONCLUSION: The study shows that individuals with HbA1c-defined
      prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion
      may be helpful to capture individuals with an increased risk of diabetes and
      cardiovascular disease who may benefit from an intensive lifestyle intervention.

PMID- 28511906
TI  - Design, synthesis and anti-tumor activity study of novel histone deacetylase
      inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding
      groups.
AB  - As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to
      lots of diseases, especially cancer. Further researches indicated that different
      HDAC isoforms played various roles in a wide range of tumor types. Herein a novel
      series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based
      zinc binding groups have been designed and synthesized through scaffold hopping
      strategy. Among these compounds, the most potent compound 9n exhibited similar if
      not better HDAC inhibition and antiproliferative activities against multiple
      tumor cell lines compared with the positive control entinostat (MS-275).
      Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163,
      0.396 and 0.605uM, respectively), compound 9n with IC50 values of 0.032, 0.256
      and 0.311uM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.

PMID- 28511907
TI  - Potential inhibitors of human carbonic anhydrase isozymes I and II: Design,
      synthesis and docking studies of new 1,3,4-thiadiazole derivatives.
AB  - In the last years, inhibition of carbonic anhydrase (CA) has emerged as a
      promising approach for pharmacologic intervention in a variety of disorders such
      as glaucoma, epilepsy, obesity, and cancer. As a consequence, the design of CA
      inhibitors (CAIs) is a highly dynamic field of medicinal chemistry. Due to the
      therapeutic potential of thiadiazoles as CAIs, new 1,3,4-thiadiazole derivatives
      were synthesized and investigated for their inhibitory effects on hCA I and hCA
      II. Although the tested compounds did not carry a sulfonamide group, an important
      pharmacophore for CA inhibitory activity, it was a remarkable finding that most
      of them were more effective on hCAs than acetazolamide (AAZ), the reference
      agent. Among these compounds, N'-((5-(4-chlorophenyl)furan-2-yl)methylene)-2-((5
      (phenylamino)-1,3,4-thiadiazol-2-yl)thio)acetohydrazide (3) was found to be the
      most effective compound on hCA I with an IC50 value of 0.14nM, whereas N'-((5-(2
      chlorophenyl)furan-2-yl)methylene)-2-((5-(phenylamino)-1,3,4-thiadiazol-2
      yl)thio)acetohydrazide (1) was found to be the most potent compound on hCA II
      with an IC50 value of 0.15nM. According to molecular docking studies, all
      compounds exhibited high affinity and good amino acid interactions similar to AAZ
      on the both active sites of hCA I and hCA II enzymes.

PMID- 28511908
TI  - Potential anti-gout constituents as xanthine oxidase inhibitor from the fruits of
      Stauntonia brachyanthera.
AB  - With the aim of finding a better xanthine oxidase inhibitor with potential anti
      gout properties, the studies on the fruit of Stauntonia brachyanthera were
      carried out, which led to the isolation of 12 glycosides, including 4 new nor
      oleanane triterpenoids. Their structures were determined by comprehensive
      spectroscopic (NMR and HR MS) analysis. Two compounds (4 and 11) exhibited
      significant inhibitory activities on xanthine oxidase with IC50 values of 5.22
      and 1.60uM, respectively. Another five compounds (1, 2, 3, 8 and 10) showed
      qualified activities. The results suggested that the existences of nor-oleanane
      triterpenoids and flavonoids in the fruits were responsible for the inhibitory
      activity on xanthine oxidase that could cut off the production of uric acid. Nor
      oleanane triterpenoids, a new leading XO inhibitor, is worthy of further studies
      on molecular biology level for its mechanisms.

PMID- 28511909
TI  - Discovery and structure-guided fragment-linking of 4-(2,3-dichlorobenzoyl)-1
      methyl-pyrrole-2-carboxamide as a pyruvate kinase M2 activator.
AB  - Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the
      pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic
      intermediates as building blocks for biosynthetic processes, and thereby
      supporting cell proliferation. Activation of PKM2 should invert aerobic
      glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has
      gained attention as a promising cancer therapy target. To obtain novel PKM2
      activators, we conducted a high-throughput screening (HTS). Among several hit
      compounds, a fragment-like hit compound with low potency but high ligand
      efficiency was identified. Two molecules of the hit compound bound at one
      activator binding site, and the molecules were linked based on the crystal
      structure. Since this linkage succeeded in maintaining the original position of
      the hit compound, the obtained compound exhibited highly improved potency in an
      in vitro assay. The linked compound also showed PKM2 activating activity in a
      cell based assay, and cellular growth inhibition of the A549 cancer cell line.
      Discovery of this novel scaffold and binding mode of the linked compound provides
      a valuable platform for the structure-guided design of PKM2 activators.

PMID- 28511910
TI  - Synthesis and biological research of novel azaacridine derivatives as potent DNA
      binding ligands and topoisomerase II inhibitors.
AB  - DNA and DNA-related enzymes are one of the most effective and common used
      intracellular anticancer targets in clinic and laboratory studies, however, most
      of DNA-targeting drugs suffered from toxic side effects. Development of new
      molecules with good antitumor activity and low side effects is important. Based
      on computer aided design and our previous studies, a series of novel azaacridine
      derivatives were synthesized as DNA and topoisomerases binding agents, among
      which compound 9 displayed the best antiproliferative activity with an IC50 value
      of 0.57MUM against U937 cells, which was slightly better than m-AMSA. In
      addition, compound 9 displayed low cytotoxicity against human normal liver cells
      (QSG-7701), the IC50 of which was more than 3 times lower than m-AMSA. Later
      study indicated that all the compounds displayed topoisomerases II inhibition
      activity at 50MUM. The representative compound 9 could bind with DNA and induce
      U937 apoptosis through the exogenous pathway.

PMID- 28511911
TI  - Sulfonamide inhibition profiles of the beta-carbonic anhydrase from the
      pathogenic bacterium Francisella tularensis responsible of the febrile illness
      tularemia.
AB  - A new beta-class carbonic anhydrase (CA, EC 4.2.1.1) has been cloned, purified
      and characterized in the genome of the pathogenic bacterium Francisella
      tularensis responsible of the febrile illness tularemia. This enzyme, FtubetaCA,
      showed a kcat of 9.8 *105s-1 and a kcat/KM of 8.9 *107M-1s-1 for the CO2
      hydration, physiological reaction, being one of the most effective beta-CAs known
      to date, with a catalytic activity only 1.68-times lower than that of the
      human(h) isoform hCA II. A panel of 39 simple aromatic and heterocyclic
      sulfonamides, as well as clinically used drugs incorporating
      sulfonamide/sulfamate zinc-binding groups, was used to investigate the inhibition
      profile of FtubetaCA with these classes of derivatives. The enzyme generally
      showed a weaker affinity for these inhibitors compared to other alpha- and beta
      CAs investigated earlier, with only acetazolamide and its deacetylated precursor
      having inhibition constant <1uM. Indeed, the two compounds acetazolamide AAZ and
      its deacetylated precursor 13 (KIs of 655-770nM), as well as metanilamide and
      methazolamide (KIs of 2.53-2.92uM), were the best FtubetaCA inhibitors detected
      so far. As the physiological role of bacterial beta-CAs is poorly understood for
      the virulence/life cycle of these pathogens, the present study may constitute a
      starting point for the design of effective pathogenic bacteria CA inhibitors with
      potential use as antiinfectives.

PMID- 28511912
TI  - Inhibition of KDM4A activity as a strategy to suppress interleukin-6 production
      and attenuate colitis induction.
AB  - 4-Chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) functions as a hapten and
      fluoresces upon binding to proteins. Therefore, fluorescence visualization of
      hapten-proteins is a feature of the colitis induced by NBD-Cl. Using this colitis
      model, we located activated fibroblasts in the vicinity of hapten-proteins upon
      colitis induction and observed interleukin (IL)-6 production in the activated
      fibroblasts. We screened herbal ingredients using primary fibroblasts stimulated
      with tumor necrosis factor alpha (TNF-alpha) and found the suppressive action of
      Atractylodin on IL-6 production. Under TNF-alpha stimulation, Atractylodin
      induced the tri-methylation of histone H3 at lysine residue 9, which impaired the
      binding between NF-kappaB and the IL-6 promoter on the genomic DNA. Atractylodin
      inhibited KDM4A but not KDM6A activity. Atractylodin administration attenuated
      colitis induction. The KDM4A inhibitor ML324 showed similar actions on IL-6
      production and colitis induction. We propose the inhibition of KDM4A activity as
      a strategy to suppress IL-6 production and attenuate colitis induction.

PMID- 28511913
TI  - The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent
      activation of the HPA axis.
AB  - The corticotropin-releasing hormone (CRH) plays an important role in mediating
      physiological response to stress and is thought to be involved in the development
      of various psychiatric disorders. In this paper, we compare the differences
      between the effect of intraperitoneal (i.p.) and intraarterial (i.a.)
      administration of the non-peptide CRH1 antagonist CP-154,526 (CP) (10 and
      20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP,
      and c-Fos expression in the paraventricular nucleus of the hypothalamus.
      Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma
      ACTH (from 105+/-13 to 278+/-51pg/ml after 20mg/kg). This effect was accompanied
      by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the
      paraventricular nucleus of the hypothalamus. When the drug was administered i.p.,
      CP-induced activation of the HPA appears to mask the inhibitory effect of CP on
      stress-induced ACTH secretion, an effect which was readily apparent when the drug
      was given i.a. Intraperitoneal administration of CP also increased the baseline
      MAP which may account for previous reports that treatment with this drug
      attenuated the increases associated with stress. CP given by either route had no
      effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies
      in which CP 154,526 is given, the route of delivery must be given careful
      consideration.

PMID- 28511914
TI  - Digitoxin increases sensitivity of glioma stem cells to TRAIL-mediated apoptosis.
AB  - Malignant glioma is one type of common malignancy in central nervous system (CNS)
      tumors which has a very bad influence on the survival quality of the patients. In
      this regard, lots of studies on improving the therapeutic effects of malignant
      glioma have been done continuously. This study takes glioma stem cells (GSCs) as
      the subject and focuses on the sensitization effect of digitoxin (DT) on the
      apoptosis mediated by TNF-related apoptosis-inducing ligand (TRAIL) to prove that
      the combination therapy of DT and TRAIL has a more active effect of inducing GSCs
      apoptosis. This study used cultured GSCs. Comparisons of single drug therapy and
      combination therapy indicated that DT had a synergistic action with TRAIL to
      produce a more active effect of inducing the apoptosis of GSCs. This effect was
      also shown in the changes of expressions of cell apoptosis pathway related
      protein markers tested by Western Blot method. In conclusion, DT had a
      sensitization effect on GSCs apoptosis mediated by TRAIL.

PMID- 28511915
TI  - Altered ionic currents and amelioration by IGF-1 and PACAP in motoneuron-derived
      cells modelling SBMA.
AB  - Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a
      motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat
      encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA
      is triggered by the binding of mutant AR to its natural ligands, testosterone and
      dihydrotestosterone (DHT). To investigate the neuronal alterations of motor
      neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ
      expansions in the AR alter cell ionic currents. We used mouse motoneuron-derived
      MN-1 cells expressing normal AR (MN24Q) and mutant AR (MN100Q treated cells with
      vehicle EtOH and DHT). We observed a reduction of the current flux mainly at
      depolarizing potentials in the DHT-treated cells, while the dissection of
      macroscopic currents showed single different cationic currents belonging to
      voltage-gated channels. Also, we treated the cells with IGF-1 and PACAP, which
      have previously been shown to protect MN-1 cells from the toxicity of mutant AR,
      and we found an amelioration of the altered currents. Our results suggest that
      the electrophysiological correlate of SBMA is a suitable reference point for the
      identification of disease symptoms and for future therapeutic targets.

PMID- 28511916
TI  - Pre-treatment with amitriptyline causes epigenetic up-regulation of
      neuroprotection-associated genes and has anti-apoptotic effects in mouse neuronal
      cells.
AB  - Antidepressants, such as imipramine and fluoxetine, are known to alter gene
      expression patterns by inducing changes in the epigenetic status of neuronal
      cells. There is also some evidence for the anti-apoptotic effect of various
      groups of antidepressants; however, this effect is complicated and cell-type
      dependent. Antidepressants of the tricyclic group, in particular amitriptyline,
      have been suggested to be beneficial in the treatment of neurodegenerative
      disorders. We examined whether amitriptyline exerts an anti-apoptotic effect via
      epigenetic mechanisms. Using DNA microarray, we analyzed global gene expression
      in mouse primary cultured neocortical neurons after treatment with amitriptyline
      and imipramine. The neuroprotection-associated genes, activating transcription
      factor 3 (Atf3) and heme oxygenase 1 (Hmox1), were up-regulated at both mRNA and
      protein levels by treatment with amitriptyline. Quantitative chromatin
      immunoprecipitation assay revealed that amitriptyline increased enrichments of
      trimethylation of histone H3 lysine 4 in the promoter regions of Atf3 and Hmox1
      and acetylation of histone H3 lysine 9 in the promoter regions of Atf3, which
      indicate an active epigenetic status. Amitriptyline pre-treatment attenuated 1
      methyl-4-phenylpyridinium ion (MPP+)- or amyloid beta peptide 1-42 (Abeta1-42)
      induced neuronal cell death and inhibited the activation of extracellular signal
      regulated kinase 1 and 2 (ERK1/2). We found that Atf3 and Hmox1 were also up
      regulated after Abeta1-42 treatment, and were further increased when pre-treated
      with amitriptyline. Interestingly, the highest up-regulation of Atf3 and Hmox1,
      at least at mRNA level, was observed after co-treatment with Abeta1-42 and
      amitriptyline, together with the loss of the neuroprotective effect. These
      findings suggest preconditioning and neuroprotective effects of amitriptyline;
      however, further investigations are needed for clarifying the contribution of
      epigenetic up-regulation of Atf3 and Hmox1 genes.

PMID- 28511917
TI  - Evidence of the role of the vagal nerves as a monitor in the gastrointestinal
      renal axis of natriuresis in human: Effects of vagotomy.
AB  - This study aimed to investigate the mechanism of gastrointestinal regulation of
      natriuresis. Sixteen subjects without (group I) and sixteen subjects with a
      truncal vagotomy (group II), were given a daily diet of 18mmol of sodium for
      5days (D1-D5). The sodium deficit for this period was calculated for each subject
      and on the morning of day-6 (D6), their cumulative deficit (E) was given as 3%
      NaCl. In both groups the subjects were divided to receive the hypertonic saline
      either orally (Ior, IIor) or intravenously (Iiv, IIiv). During the period of low
      sodium diet when compared to group II subjects of group I (1) had a greater
      weight loss (p<0.005), (2) demonstrated a larger drop in pulse pressure
      (p<0.005), (3) achieved a positive sodium equilibrium later (D5 vs D4) and (4)
      developed a greater sodium deficit (p<0.005). During the two 12h periods of D6,
      both Ior and Iiv exhibited greater natriuresis during the first 12h period
      (p<0.0001) whereas both IIor and IIiv did so during the second 12h period
      (p<0.0001). On D6 Ior excreted the greatest percentage of E (E%; 35.63%+/-3.12%,
      p<0.0001) compared to Iiv (17.06%+/-1.78%), IIor (16.03%+/-3.54%) and IIiv
      (15.39%+/-2.77%) whereas E% was not different between the other subgroups. These
      results indicate that the differential natriuresis between oral and intravenous
      sodium loading in previously sodium deprived subjects, is due to a mechanism in
      which the vagal nerves play a significant role as part of neural reflex or via a
      natriuretic hormone.

PMID- 28511919
TI  - The debate: Treatment after the first seizure-The PRO.
AB  - According to current diagnosis criteria, first seizures constitute beginning
      epilepsy when they carry recurrence risks of >=60% over the next 10 years. This
      is frequently the case and warrants AED treatment. Evidence argues against
      deferring treatment when provoking factors such as sleep deprivation are
      reported. There are several characteristics of first seizures which markedly
      increase recurrence risk but not clearly beyond 60%. This includes status
      epilepticus or seizure flurries at first manifestation or focal semiology
      indicating focal epilepsy. In this situation, there are still various medical,
      social and individual aspects supporting early initiation of AED. Modern AED
      allow this safely and at low dosages.

PMID- 28511920
TI  - The Girls-Only HPV Vaccination Program in British Columbia, Canada: A Qualitative
      Study Exploring Expert Informants' Perspectives of Input From the Public.

PMID- 28511918
TI  - Molecular imaging of serotonin degeneration in mild cognitive impairment.
AB  - Neuropathological and neuroimaging studies have consistently demonstrated
      degeneration of monoamine systems, especially the serotonin system, in normal
      aging and Alzheimer's disease. The evidence for degeneration of the serotonin
      system in mild cognitive impairment is limited. Thus, the goal of the present
      study was to measure the serotonin transporter in vivo in mild cognitive
      impairment and healthy controls. The serotonin transporter is a selective marker
      of serotonin terminals and of the integrity of serotonin projections to cortical,
      subcortical and limbic regions and is found in high concentrations in the
      serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty
      eight participants with mild cognitive impairment (age 66.6+/-6.9, 16 males) and
      28 healthy, cognitively normal, demographically matched controls (age 66.2+/-7.1,
      15 males) underwent magnetic resonance imaging for measurement of grey matter
      volumes and high-resolution positron emission tomography with well-established
      radiotracers for the serotonin transporter and regional cerebral blood flow. Beta
      amyloid imaging was performed to evaluate, in combination with the
      neuropsychological testing, the likelihood of subsequent cognitive decline in the
      participants with mild cognitive impairment. The following hypotheses were
      tested: 1) the serotonin transporter would be lower in mild cognitive impairment
      compared to controls in cortical and limbic regions, 2) in mild cognitive
      impairment relative to controls, the serotonin transporter would be lower to a
      greater extent and observed in a more widespread pattern than lower grey matter
      volumes or lower regional cerebral blood flow and 3) lower cortical and limbic
      serotonin transporters would be correlated with greater deficits in auditory
      verbal and visual-spatial memory in mild cognitive impairment, not in controls.
      Reduced serotonin transporter availability was observed in mild cognitive
      impairment compared to controls in cortical and limbic areas typically affected
      by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum
      and thalamus that are relatively spared in Alzheimer's disease. The reduction of
      the serotonin transporter in mild cognitive impairment was greater than grey
      matter atrophy or reductions in regional cerebral blood flow compared to
      controls. Lower cortical serotonin transporters were associated with worse
      performance on tests of auditory-verbal and visual-spatial memory in mild
      cognitive impairment, not in controls. The serotonin system may represent an
      important target for prevention and treatment of MCI, particularly the post
      synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as
      presynaptic aspects of the serotonin system, as indicated by the observation of
      lower serotonin transporters in MCI relative to healthy controls.

PMID- 28511922
TI  - Simultaneous Transseptal Para-Ring Leak Closure and Transcatheter Mitral Valve
      Implantation for the Treatment of Surgical Mitral Repair Failure.
AB  - Repeat cardiac surgery in patients with a previous sternotomy is associated with
      significant morbidity and mortality. While transcatheter aortic valve
      implantation in high risk surgical patients is now well established, experience
      with transcatheter mitral valve replacement is still at an early stage. Although
      many successful reports of transcatheter mitral valve replacements now exist, the
      predominant approach has been via a transapical approach. It is likely that, as
      with the evolution of favoured access routes for transcatheter aortic therapies,
      future directions for transcatheter mitral valves will focus on smaller delivery
      systems favouring the transvenous transseptal approach where possible. We present
      the first reported case of combined transseptal para-ring leak closure followed
      by transcatheter mitral valve implantation using a 12/5mm Amplatzer III vascular
      plug and a 29mm SAPIEN 3 valve.

PMID- 28511923
TI  - IgG4-Aortopathy: An Underappreciated Cause of Non-Infectious Thoracic Aortitis.
AB  - IgG4 related thoracic aortitis is a recent addition to the differential diagnosis
      for inflammatory aortic disease - a condition which is often underappreciated
      until complications arise such as aneurysmal formation or aortic dissection.
      Currently, IgG4 aortitis remains a post-surgical diagnosis reliant on positive
      immunohistochemistry findings. Management is guided by the extent of disease
      involvement, which can be gauged by serum IgG4 levels and radiological findings.
      Options include surgical resection, corticosteroid therapy and steroid-sparing
      agents to prevent relapses.

PMID- 28511924
TI  - Evaluation of the Effectiveness of a Phone Based Care Coordination Pilot on
      Hospital Utilisation and Costs for Patients With Chest Pain.
AB  - BACKGROUND: A small percentage of the population represents a disproportionate
      number of attendances at emergency departments (ED). "Frequent presenters" to ED
      with chest pain do not always fit into established pathways for acute myocardial
      events. With accelerated "rule out" protocols, patients are often discharged from
      the ED after short lengths of stay. This research will evaluate the effectiveness
      of a phone based care-coordination pilot designed to meet the needs of patients
      attending ED with cardiac and non-cardiac chest pain. METHODS: A longitudinal,
      single-arm interventional study with retrospectively recruited control group.
      Ninety-five patients were enrolled as the intervention group; 97 patients were
      retrospectively identified as controls. These patients had re-presented with
      chest pain within 6 months of a cardiac event, or attended hospital within 12
      months two or more times with chest pain and/or complex needs. Intervention group
      patients were holistically assessed then phone-coached to support self-management
      of chest pain over 6 months. Following descriptive and univariate analysis,
      multivariate analysis was conducted to adjust for noted differences between the
      intervention and control groups. RESULTS: Thirty-day representation to ED was
      significantly less for the intervention group (14.1%) compared to controls
      (27.7%). After adjusting for baseline differences, intervention patients were
      more than two-fold less likely to re-present compared to controls (OR=0.42,
      95%CI: 0.19-0.96). After adjustment for baseline differences, the savings in
      subsequent inpatient costs was $1588 per person, as a result of intervention,
      patients were less likely to have inpatient readmissions (16.3%) compared to
      controls (20.2%), although this was not statistically significant (p=0.588).
      CONCLUSION: A phone based care-coordination pilot with targeted interventions has
      the potential to reduce ED presentations and hospital readmissions among patients
      representing with chest pain.

PMID- 28511926
TI  - Fresh, frozen, or ambient food equivalents and their impact on food waste
      generation in Dutch households.
AB  - In Europe, it is estimated that more than 50% of total food waste - of which most
      is avoidable - is generated at household level. Little attention has been paid to
      the impact on food waste generation of consuming food products that differ in
      their method of food preservation. This exploratory study surveyed product
      specific possible impacts of different methods of food preservation on food waste
      generation in Dutch households. To this end, a food waste index was calculated to
      enable relative comparisons of the amounts of food waste from the same type of
      foods with different preservation methods on an annual basis. The results show
      that, for the majority of frozen food equivalents, smaller amounts were wasted
      compared to their fresh or ambient equivalents. The waste index (WI) proposed in
      the current paper confirms the hypothesis that it may be possible to reduce the
      amount of food waste at household level by encouraging Dutch consumers to use
      (certain) foods more frequently in a frozen form (instead of fresh or ambient).
      However, before this approach can be scaled to population level, a more detailed
      understanding of the underlying behavioural causes with regard to food
      provisioning and handling and possible interactions is required.

PMID- 28511921
TI  - Myeloperoxidase: A new player in autoimmunity.
AB  - Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules
      of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other
      reactive moieties, which kill pathogens during infections. In contrast, in the
      setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be
      pathogenic, promoting inflammation and causing tissue damage. In contrast,
      evidence also exists that MPO can limit the extent of immune responses. Elevated
      MPO levels and activity are observed in a number of autoimmune diseases including
      in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of
      rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving
      autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby
      MPO is thought to contribute to disease pathogenesis include tuning of adaptive
      immune responses and/or the induction of vascular permeability.

PMID- 28511925
TI  - Total Correction of Tetralogy of Fallot at Early Age: A Study of 183 Cases.
AB  - BACKGROUND: Opinions regarding the optimal time for the repair of tetralogy of
      Fallot vary. A debate also exists about the timing of repair for the asymptomatic
      infant. METHODS: This study included 183 patients with tetralogy of Fallot. All
      patients were subjected to clinical examination with measurement of oxygen
      saturation, 12-lead ECG, plain chest x-ray, and complete laboratory
      investigation. Echocardiography and cardiac catheterisation were indicated if
      there was an inability to reach diagnosis by echocardiography, suspicion of
      coronary anomaly, evaluation of distal pulmonary arteries or suspicion of major
      aorto-pulmonary collaterals. Complete repair was done in all patients. Patients
      were divided into two groups for comparison. Group 1 (147 patients, 1-year-old or
      less), and Group 2 (36 patients older than 1 year). RESULTS: Three patients died
      in Group1 (2.04%) while there was no early mortality in Group 2 patients. Six
      patients in Group 1 (4.08%) were reoperated for significant residual or recurrent
      right ventricular outflow stenosis, three patients (2.04%) were reoperated for
      residual significant shunt, and three patients (2.04%) were reoperated for
      residual significant stenosis and residual significant shunt. That is in addition
      to three patients (2.04%) who had significant tricuspid regurgitation, three more
      patients (2.04%) who needed a permanent pacemaker implantation, and nine patients
      (6.1%) who had significant postoperative pulmonary valve regurgitation. On the
      other hand, for Group 2 patients, there were only three patients who were
      reoperated for postoperative restenosis and significant shunt, three patients who
      were reoperated for permanent pacemaker implantation, and another two patients
      who had insignificant restenosis to be followed up. CONCLUSIONS: Early complete
      tetralogy of Fallot repair can be accomplished with a low mortality.

PMID- 28511927
TI  - Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer
      through long-range chromatin interactions.
AB  - Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 genes encode a family
      of interferon (IFN)-induced transmembrane proteins that block entry of a broad
      spectrum of pathogens. However, the transcriptional regulation of these genes,
      especially whether there exist any enhancers and their roles during the IFN
      induction process remain elusive. Here, through public data mining, episomal
      luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified
      an IFN-responsive enhancer located 35kb upstream of IFITM3 gene promoter
      upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin
      immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and
      luciferase reporter assay demonstrated that signal transducers and activators of
      transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was
      indispensable for the enhancer activity. Furthermore, using chromosome
      conformation capture technique, we revealed that the IFITM1, 2 and 3 genes
      physically clustered together and constitutively looped to the distal enhancer
      through long-range interactions in both HEK293 and A549 cells, providing
      structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer.
      Finally, we showed that in vivo truncation of the enhancer impaired IFN-induced
      resistance to influenza A virus (IAV) infection. These findings expand our
      understanding of the mechanisms underlying the transcriptional regulation of
      IFITM1, 2 and 3 expression and its ability to mediate IFN signaling.

PMID- 28511929
TI  - Clinical Characteristics of Pertussis-Associated Cough in Adults and Children: A
      Diagnostic Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Pertussis (whooping cough) is a highly infective cause of cough that
      causes significant morbidity and mortality. Existing case definitions include
      paroxysmal cough, whooping, and posttussive vomiting, but diagnosis can be
      difficult. We determined the diagnostic accuracy of clinical characteristics of
      pertussis-associated cough. METHODS: We systematically searched CINAHL, Embase,
      Medline, and SCI-EXPANDED/CPCI-S up to June 2016. Eligible studies compared
      clinical characteristics in those positive and negative for Bordetella pertussis
      infection, confirmed by laboratory investigations. Two authors independently
      completed screening, data extraction, and quality and bias assessments. For each
      characteristic, RevMan was used to produce descriptive forest plots. The
      bivariate meta-analysis method was used to generate pooled estimates of
      sensitivity and specificity. RESULTS: Of 1,969 identified papers, 53 were
      included. Forty-one clinical characteristics were assessed for diagnostic
      accuracy. In adult patients, paroxysmal cough and absence of fever have a high
      sensitivity (93.2% [CI, 83.2-97.4] and 81.8% [CI, 72.2-88.7], respectively) and
      low specificity (20.6% [CI, 14.7-28.1] and 18.8% [CI, 8.1-37.9]), whereas
      posttussive vomiting and whooping have low sensitivity (32.5% [CI, 24.5-41.6] and
      29.8% [CI, 8.0-45.2]) and high specificity (77.7% [CI, 73.1-81.7] and 79.5% [CI,
      69.4-86.9]). Posttussive vomiting in children is moderately sensitive (60.0% [CI,
      40.3-77.0]) and specific (66.0% [CI, 52.5-77.3]). CONCLUSIONS: In adult patients,
      the presence of whooping or posttussive vomiting should rule in a possible
      diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of
      fever should rule it out. In children, posttussive vomiting is much less helpful
      as a clinical diagnostic test.

PMID- 28511930
TI  - Bed morphological features associated with an optimal slurry concentration for
      reproducible preparation of efficient capillary ultrahigh pressure liquid
      chromatography columns.
AB  - Column wall effects and the formation of larger voids in the bed during column
      packing are factors limiting the achievement of highly efficient columns.
      Systematic variation of packing conditions, combined with three-dimensional bed
      reconstruction and detailed morphological analysis of column beds, provide
      valuable insights into the packing process. Here, we study a set of sixteen 75MUm
      i.d. fused-silica capillary columns packed with 1.9MUm, C18-modified, bridged
      ethyl hybrid silica particles slurried in acetone to concentrations ranging from
      5 to 200mg/mL. Bed reconstructions for three of these columns (representing low,
      optimal, and high slurry concentrations), based on confocal laser scanning
      microscopy, reveal morphological features associated with the implemented slurry
      concentration, that lead to differences in column efficiency. At a low slurry
      concentration, the bed microstructure includes systematic radial heterogeneities
      such as particle size-segregation and local deviations from bulk packing density
      near the wall. These effects are suppressed (or at least reduced) with higher
      slurry concentrations. Concomitantly, larger voids (relative to the mean particle
      diameter) begin to form in the packing and increase in size and number with the
      slurry concentration. The most efficient columns are packed at slurry
      concentrations that balance these counteracting effects. Videos are taken at low
      and high slurry concentration to elucidate the bed formation process. At low
      slurry concentrations, particles arrive and settle individually, allowing for
      rearrangements. At high slurry concentrations, they arrive and pack as large
      patches (reflecting particle aggregation in the slurry). These processes are
      discussed with respect to column packing, chromatographic performance, and bed
      microstructure to help reinforce general trends previously described. Conclusions
      based on this comprehensive analysis guide us towards further improvement of the
      packing process.

PMID- 28511931
TI  - Water-compatible micron-sized monodisperse molecularly imprinted beads for
      selective extraction of five iridoid glycosides from Cornus officinalis fructus.
AB  - An efficient, accurate and sensitive method for the determination of five iridoid
      glycosides (IGs) in Cornus officinalis fructus using molecularly imprinted solid
      phase extraction (MISPE) coupled with high performance liquid chromatography
      (HPLC) has been developed. Water-compatible molecularly imprinted beads (MIBs)
      were synthesized by precipitation polymerization, using alkenyl glycosides
      glucose as the hydrophilic functional monomer. Scanning electron microscopy
      showed that the MIBs had a narrow particle size distribution, with diameters in
      the range 7.5-9.3MUm. The special molecular recognition by the MIBs of IGs in
      aqueous media was verified by static adsorption, kinetic adsorption, and
      selectivity experiments. The newly prepared MIBs were used as sorbents in solid
      phase extraction (SPE) for the selective recognition of five IGs (loganin,
      morroniside, loganic acid, 7-O-ethyl-morroniside and 7-O-methyl morroniside) in
      Cornus officinalis fructus. When optimized, the MISPE-HPLC method had good
      linearity (0.02-100mgg-1), with correlation coefficient (R)>=0.994. Recoveries at
      three spiked levels were in the range 80.0%-94.0%. Because of its excellent
      specificity and hydrophilicity, SPE based on monodisperse MIBs provides a
      promising pretreatment strategy for the analysis of active components in natural
      products, especially for the quality control of traditional Chinese medicines.

PMID- 28511932
TI  - Determination of piperidinium ionic liquid cations in environmental water samples
      by solid phase extraction and hydrophilic interaction liquid chromatography.
AB  - This paper presents a novel analytical method for the determination of
      piperidinium ionic liquid cations in environmental water by hydrophilic
      interaction liquid chromatography and solid-phase extraction technology. The left
      standing, centrifuged and filtered river water samples were first purified and
      concentrated through the C18 solid phase extraction column, and eluted with
      0.02mol/L hydrochloric acid prepared in methanol and deionized water (80/20,
      v/v). Then the eluents were analyzed by a hydrophilic column combined with
      0.8mmol/L 1-propyl-3-methyl imidazolium tetrafluoroborate aqueous
      solution/acetonitrile (40/60, v/v) as the mobile phase and indirect ultraviolet
      detection. The detection limits of piperidinium cations were less than 0.4mg/L.
      The relative standard deviations were less than 0.6%. The method has been
      successfully applied to the determination of piperidinium cations in Songhua
      River water samples. Recoveries were 80.0%-98.3%. This research may provide a
      reference for studying the environmental effect of ionic liquids.

PMID- 28511933
TI  - An initial demonstration of hierarchically porous niobium alkylphosphonates
      coordination polymers as potent radioanalytical separation materials.
AB  - Combining the merits of soft-templating and perchlorate oxidation methods, the
      first-case investigation of niobium alkylphosphonates has uncovered their unique
      morphology, backbone composition, thermal behavior and huge potentiality as
      radioanalytical separation materials. These hierarchically porous solids are
      random aggregates of densely stacked nanolayers perforated with worm-like holes
      or vesicular voids, manifesting the massif-, tower-like "polymer brush" elevated
      up to ~150nm driven by the minimal surface free energy principle. These
      coordination polymers consist of distorted niobium (V) ions strongly linked with
      tetrahedral alkylphosphonate building units, exposing uncoordinated phosphonate
      moieties and defective metal sites. Despite the amorphous features, they
      demonstrate multimodal porosity covering continuous micropores, segregated
      mesopores and fractional macropores, beneficial for the sequestration by active
      Lewis acid-base center. Evidenced by the maximum distribution coefficients of
      thorium, lanthanides reaching 9.0*104, 9.5*104mLg-1 and large separation factor
      at pH<=1 20-element cocktail, this category of niobium alkylphosphonates are
      capable of harvesting thorium, lanthanides directly from the radionuclide
      surrogate, comparable to or even surpass the performance of the metal (IV)
      arylphosphonates counterparts. They also display appreciable SFEu/Sm ~20 in 1molL
      1 HNO3, shedding light on dual approaches to achieve the isolation of americium
      from curium. A combinatorial radioanalytical separation protocol has been
      proposed to enrich thorium and europium, revealing facile utilization of these
      highly stable, phosphonated hybrids in sustainable development of radioanalytical
      separation.

PMID- 28511928
TI  - Rational design of nanoparticles towards targeting antigen-presenting cells and
      improved T cell priming.
AB  - Vaccination is a promising strategy to trigger and boost immune responses against
      cancer or infectious disease. We have designed, synthesized and characterized
      aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to
      investigate how the nature of protein association (adsorbed versus entrapped) and
      polymer/surfactant concentrations impact on the generation and modulation of
      antigen-specific immune responses. The ability of the NP formulations to target
      dendritic cells (DC), be internalized and activate the T cells was characterized
      and optimized in vitro and in vivo using markers of DC activation and co
      stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination
      with the engraftment of CD4+ and CD8+ T cells, carrying a transgenic OVA
      responding T cell receptor (TCR), to trace and characterize the activation of
      antigen-specific CD4+ and CD8+ lymph node T cells upon NP vaccination.
      Accordingly, the phenotype and frequency of immune cell stimulation induced by
      the NP loaded with OVA, isolated or in combination with synthetic unmethylated
      cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were
      characterized. DC-NP interactions increased with incubation time, presenting
      internalization values between 50 and 60% and 30-40%, in vitro and in vivo,
      respectively. Interestingly, animal immunization with antigen-adsorbed NP up
      regulated major histocompatibility complex (MHC) class II (MHCII), while NP
      entrapping the antigen up-regulated MHCI, suggesting a more efficient cross
      presentation. On the other hand, rather surprisingly, the surfactant used in the
      NP formulation had a major impact on the activation of antigen presenting cells
      (APC). In fact, DC collected from lymph nodes of animals immunized with NP
      prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed
      significantly higher levels of CD86, MHCI and MHCII. In addition, those NP
      prepared with PVA and co-entrapping OVA and the toll-like receptor (TLR) ligand
      CpG, induced the most profound antigen-specific T cell response, by both CD4+ and
      CD8+ T cells, in vivo. Overall, our data reveal the impact of NP composition and
      surface properties on the type and extension of induced immune responses. Deeper
      understanding on the NP-immune cell crosstalk can guide the rational development
      of nano-immunotherapeutic systems with improved and specific therapeutic efficacy
      and avoiding off-target effects.

PMID- 28511934
TI  - Repeated manganese administration produced abnormal expression of circadian clock
      genes in the hypothalamus and liver of rats.
AB  - Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment
      like Parkinson's disease (PD), and is called as Manganism. Circadian disruption
      is a non-motor symptom found in PD and Manganism. Clock genes are essential to
      drive and maintain circadian rhythm, but little is known about Mn exposure on
      circadian clock genes expression. Both the brain and liver are targets of Mn, we
      hypothesize that repeated Mn administration could affect clock gene expression in
      the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally
      injected Mn2+ 1mg and 5mg/kg as MnCl2.4H2O, every other day for 30 days. Mn
      neurotoxicity was evaluated by behavioral changes and loss of dopaminergic
      neurons via immunohistochemistry. The expression of circadian clock genes was
      determined via RT-qPCR. Repeated Mn administration dose-dependently retarded the
      body weight gain, impaired the rotarod activity, decreased the number of
      dopaminergic neurons in the substantia nigra, and activated microglia in the
      brain. Expressions of circadian core genes brain and muscle Arnt-like protein-1
      (Bmal1), locomotor output cycles kaput (Clock) and neuronal PAS domain protein2
      (Npas2), and clock feedback gene cryptochrome1 (Cry1), period genes (Per1 and
      Per2) in the hypothalamus and liver were decreased after exposure to Mn in a dose
      dependent manner, while expressions of clock-targeted genes nuclear receptor Rev
      Erbalpha (Nr1d1) and D-box-binding protein (Dbp) were increased. Peripheral clock
      in the liver appears to be more susceptible to Mn-induced abnormal clock gene
      expression. In summary, repeated Mn administration produced dysregulation of
      circadian clock gene expressions in both the brain and liver.

PMID- 28511935
TI  - Bile acids and male fertility: From mouse to human?
AB  - Next to their involvement in digestion, bile acids have been defined as signaling
      molecules. They have been demonstrated to control many physiological functions
      among which lipid homeostasis, glucose and energy metabolisms. Bile acids are
      ligands of several receptors and multiple studies using transgenic mouse models
      defined the major roles of their respective nuclear and membrane receptors namely
      the Farnesoid-X-Receptor (FXRalpha) and the G-protein-coupled bile acid receptor
      1(GPBAR1; TGR5). Here we review the reports highlighting the impacts of bile
      acids on testicular physiology and on male reproductive functions. The studies on
      mouse models open perspectives to better understand the deleterious effects of
      bile acids on testicular pathophysiologies and fertility disorders. Additional
      studies are needed to corroborate these correlations in humans.

PMID- 28511936
TI  - Biotechnologies for Marine Oil Spill Cleanup: Indissoluble Ties with
      Microorganisms.
AB  - The ubiquitous exploitation of petroleum hydrocarbons (HCs) has been accompanied
      by accidental spills and chronic pollution in marine ecosystems, including the
      deep ocean. Physicochemical technologies are available for oil spill cleanup, but
      HCs must ultimately be mineralized by microorganisms. How environmental factors
      drive the assembly and activity of HC-degrading microbial communities remains
      unknown, limiting our capacity to integrate microorganism-based cleanup
      strategies with current physicochemical remediation technologies. In this review,
      we summarize recent findings about microbial physiology, metabolism and ecology
      and describe how microbes can be exploited to create improved biotechnological
      solutions to clean up marine surface and deep waters, sediments and beaches.

PMID- 28511937
TI  - Hot Start to European Pluripotent Stem Cell Banking.
AB  - Achieving consistency in standards of access to and quality of human induced
      pluripotent stem cells has lagged behind their use. In Europe, a network of
      academic and industrial partners has been established to overcome this challenge.
      The experience reveals the devil in the detail of worthy ambitions informing
      future efforts.

PMID- 28511938
TI  - Floating marine litter as a raft for drifting voyages for Planes minutus
      (Crustacea: Decapoda: Grapsidae) and Liocarcinus navigator (Crustacea: Decapoda:
      Polybiidae).
AB  - The Columbus crab Planes minutus and Arch-fronted swimming crab Liocarcinus
      navigator, within their distribution ranges in the Mediterranean, were found
      rafted on plastic macro-litter floating on the open south Adriatic. While P.
      minutus was recorded from inanimate flotsam outside of the Mediterranean, L.
      navigator is herein reported for the first time on floating marine litter. The
      role of floating litter as habitat or as a dispersal agent for marine
      invertebrates has received quite attention however, records of decapod crabs
      drifting on litter has been relatively sparse. Our results suggests that vast
      quantities of floating debris, comprised primarily of non-biodegradable plastic
      polymers, probably will augment natural floating substrates in the marine
      environment, potentially facilitating the spread of invasive species. The
      dispersion of rafting crabs through floating debris should be investigated given
      the high potential ecological risk of invasion by exotic species due to the
      increase in waste production (ecological risk assessment).

PMID- 28511939
TI  - Droplet and bubble formation of combined oil and gas releases in subsea blowouts.
AB  - Underwater blowouts from gas and oil operations often involve the simultaneous
      release of oil and gas. Presence of gas bubbles in jets/plumes could greatly
      influence oil droplet formation. With the aim of understanding and quantifying
      the droplet formation from Deepwater Horizon blowout (DWH) we developed a new
      formulation for gas-oil interaction with jets/plumes. We used the jet-droplet
      formation model VDROP-J with the new module and the updated model was validated
      against laboratory and field experimental data. Application to DWH revealed that,
      in the absence of dispersant, gas input resulted in a reduction of d50 by up to
      1.5mm, and maximum impact occurred at intermediate gas fractions (30-50%). In the
      presence of dispersant, reduction in d50 due to bubbles was small because of the
      promoted small sizes of both bubbles and droplets by surfactants. The new
      development could largely enhance the prediction and response to oil and gas
      blowouts.

PMID- 28511940
TI  - Comparative efficacy of benthic biotic indices in assessing the Ecological
      Quality Status (EcoQS) of the stressed Ulhas estuary, India.
AB  - Ecostatus of Ulhas estuary, one of the most polluted estuaries along the
      industrialized and urbanized northwest coast of India, was evaluated by six
      widely accepted benthic indices viz. H'(log2), AMBI, M-AMBI, BENTIX, BOPA and
      BO2A to test their efficiency in a tropical setting. The mesohaline zone, which
      presented eutrophic conditions, was classified as 'bad' by all indices due to the
      azoic status. Despite significant correlations obtained between indices, there
      were discrepancies in the accurate level of EcoQS assigned to each station. AMBI
      was observed to be most efficient in indicating a clear spatial variability from
      a 'poor' to 'bad' ecological quality status in the middle and upstream zones to
      an improved status in the downstream region. Limitations of all indices are
      discussed in light of their suitability for assessing the estuarine environmental
      condition. The present results could provide a fillip to environmental
      improvement initiatives currently being undertaken in the estuary.

PMID- 28511941
TI  - Effects of ocean acidification on the physiological performance and carbon
      production of the Antarctic sea ice diatom Nitzschia sp. ICE-H.
AB  - Ocean acidification (OA) resulting from increasing atmospheric CO2 strongly
      influences marine ecosystems, particularly in the polar ocean due to greater CO2
      solubility. Here, we grew the Antarctic sea ice diatom Nitzschia sp. ICE-H in a
      semicontinuous culture under low (~400ppm) and high (1000ppm) CO2 levels.
      Elevated CO2 resulted in a stimulated physiological response including increased
      growth rates, chlorophyll a contents, and nitrogen and phosphorus uptake rates.
      Furthermore, high CO2 enhanced cellular particulate organic carbon production
      rates, indicating a greater shift from inorganic to organic carbon. However, the
      cultures grown in high CO2 conditions exhibited a decrease in both extracellular
      and intracellular carbonic anhydrase activity, suggesting that the carbon
      concentrating mechanisms of Nitzschia sp. ICE-H may be suppressed by elevated
      CO2. Our results revealed that OA would be beneficial to the survival of this sea
      ice diatom strain, with broad implications for global carbon cycles in the future
      ocean.

PMID- 28511943
TI  - Relationship between soluble CD25 and gene expression in healthy individuals and
      patients with multiple sclerosis.
AB  - Genome wide association studies and fine mapping has established a firm link
      between the IL2RA gene, encoding the interleukin-2 receptor alpha-chain CD25, and
      susceptibility to multiple sclerosis (MS). We hypothesized that gene expression
      in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and MS
      patients are associated with IL2RA SNP rs2104286 and that gene expression levels
      correlate with soluble CD25 (sCD25) concentrations - that are affected by
      rs2104286. We used the Affymetrix Human Gene ST 1.0 microarray to analyze gene
      expression levels in PBMCs from 18 HCs and 51MS patients. Plasma concentrations
      of sCD25 were measured by ELISA in all individuals. In HCs 266 genes correlated
      with sCD25 with Spearman's rho>=0.707; 70 of these genes had a false discovery
      rate (FDR) value of q<0.05. These genes were highest expressed in cells belonging
      to the innate immune system. Gene-networks were focused around NFKB1, TNF, BCL6
      and STAT1. Eighteen genes correlated with sCD25 with rho>=0.707 in relapsing
      remitting MS versus 33 in secondary progressive and 34 in primary progressive MS.
      None had a FDR<0.05. Thirty-eight and 23 genes were differentially expressed
      between rs2104286 genotype-groups in MS patients and HCs respectively, however
      they were not significant after FDR correction. Our study indicates that
      rs2104286 influences gene expression in PBMCs in HCs as shown by the high
      correlations with the rs2104286-affected sCD25 protein. Correlations were
      strongest in HCs suggesting that immunological alterations may obscure the role
      of the IL2RA SNP rs2104286 in established MS.

PMID- 28511942
TI  - Effect of resistant and digestible rice starches on human cytokine and lactate
      metabolic networks in serum.
AB  - Resistant starch generated after treating ordinary starch is of great
      significance to human health in the countries with overnutrition. However, its
      functional evaluation in the human body has been rarely reported. By determining
      the lactate metabolic flux, 12 serum enzymes expression level and 38 serum
      cytokines in healthy volunteers, the variation in cytokine network and lactate
      metabolic network in serum were investigated to compare the mechanism of the
      physiological effects between the two starches. The results indicated that
      compared with digestible starch, resistant starch had anti-inflammatory effects,
      increased anabolism, and decreased catabolism. Further, the intercellular
      communication networks including cytokine and lactate metabolic networks were
      mapped out. The relationship suggested that resistant starch might affect and
      control the secretion of cytokines to regulate lactate metabolic network in the
      body, promoting the development of immunometabolism.

PMID- 28511944
TI  - Serum periostin in patients hospitalized for COPD exacerbations.
AB  - Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory
      response in patients with asthma, but its predictive role in hospitalized
      patients with COPD has not been evaluated. The aim of the present observational
      prospective cohort study was to evaluate the possible role of serum periostin as
      predictor of outcome in COPD patients hospitalized for AECOPD. Serum periostin
      was measured on admission and at discharge in patients admitted to the hospital
      for a COPD exacerbation. Patients were followed-up for 1year for future
      exacerbations, hospitalizations and mortality. 155 consecutive patients admitted
      to the hospital for AECOPD were included to the study. Periostin levels on
      admission were elevated compared to discharge [34.7 (25.2-52.2) vs. 25.9 (17.4
      41.0) ng/mL, p=0.003], but serum periostin levels did not differ between patients
      with or without prolonged hospitalization, or those who required non-invasive
      ventilation, intubation, or died during hospitalization. Frequent exacerbators
      had higher serum periostin levels at the time of discharge compared to non
      frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p<0.001].
      Periostin levels above the median value (25ng/mL) were not related to the time of
      next exacerbation, time of next COPD hospitalization, (p=0.858) or time to death.
      The role of serum periostin levels as a predictive biomarker of future risk in
      hospitalized patients with COPD is of limited value.

PMID- 28511945
TI  - Low Rates of Aseptic Tibial Loosening in Obese Patients With Use of High
      Viscosity Cement and Standard Tibial Tray: 2-Year Minimum Follow-Up.
AB  - BACKGROUND: Total knee arthroplasty is overall a very successful surgery, but
      complications do occur. These complications include aseptic loosening of the
      tibial component, and obese patients are among the highest risk group. High
      viscosity cement (HVC) has been implicated as a possible cause for aseptic
      loosening of the tibial component. The purpose of this study was to evaluate the
      incidence of aseptic loosening of the tibial component in obese patients with the
      use of HVC and standard tibial tray. METHODS: We identified 1366 obese patients
      (1851 knees) with a body mass index >35 kg/m2 and 2-year minimum follow-up who
      underwent primary total knee arthroplasty using HVC and a symmetrical, grit
      blasted, cobalt-chrome tibial component with 40-mm stem. Preoperative and
      postoperative range of motion, Knee Society (KS) scores, complications, and
      reoperations were evaluated. Specifically, we assessed the rate of tibial aseptic
      loosening. RESULTS: At a mean 5.4 years follow-up, only 1 in 1851 knees had
      aseptic loosening of the tibial component for an incidence of 0.054%. There was a
      mean increase of 3.3 degrees of knee range of motion. KS pain level decreased by
      38.6 points (50 point scale). KS clinical scores improved by 52.2, Knee Society
      functional scores improved by 19.5, University of California, Los Angeles,
      activity score improved by 0.9, and Oxford Knee Score by 15.7. All these
      improvements were statistically significant with P < .001. CONCLUSION: Standard
      tibial components and HVC can be used in most patients, including the high-risk
      obese group, with low rates of tibial aseptic loosening.

PMID- 28511946
TI  - National Incidence of Patient Safety Indicators in the Total Hip Arthroplasty
      Population.
AB  - BACKGROUND: The Centers for Medicare & Medicaid Services use the incidence of
      patient safety indicators (PSIs) to determine health care value and hospital
      reimbursement. The national incidence of PSI has not been quantified in the total
      hip arthroplasty (THA) population, and it is unknown if patient insurance status
      is associated with PSI incidence after THA. METHODS: All patients in the
      Nationwide Inpatient Sample (NIS) who underwent THA in 2013 were identified using
      the International Classification of Diseases, Ninth Revision, Clinical
      Modification codes. The incidence of PSI was determined using the International
      Classification of Diseases, Ninth Revision, diagnosis code algorithms published
      by the Centers for Medicare & Medicaid Services and the Agency for Healthcare
      Research and Quality. The association of insurance status and the incidence of
      PSI during the inpatient episode was determined by comparing privately insured
      and Medicare patients with Medicaid/self-pay patients using a logistic regression
      model that controlled for patient demographics, patient comorbidities, and
      hospital characteristics. RESULTS: In 2013, the NIS included 68,644
      hospitalizations with primary THA performed during the inpatient episode. During
      this period, 429 surgically relevant PSI were recorded in the NIS. The estimated
      national incidence rate of PSI after primary THA was 0.63%. In our secondary
      analysis, the privately insured cohort had significantly lower odds of
      experiencing one or more PSIs relative to the Medicaid/self-pay cohort (odds
      ratio, 0.47; 95% confidence interval, 0.29-0.76). CONCLUSION: The national
      incidence of PSI among THA patients is relatively low. However, primary insurance
      status is associated with the incidence of one or more PSIs after THA. As value
      based payment becomes more widely adopted in the United States, quality
      benchmarks and penalty thresholds need to account for these differences in risk
      adjustment models to promote and maintain access to care in the underinsured
      population.

PMID- 28511947
TI  - Intraoperative Femur Fracture Risk During Primary Direct Anterior Approach
      Cementless Total Hip Arthroplasty With and Without a Fracture Table.
AB  - BACKGROUND: There is no study to date comparing intraoperative femur fractures
      (IFFs) in the direct anterior approach (DAA) with and without a fracture table.
      We hypothesize that there is no significant difference in the IFF with and
      without a fracture table when performed by experienced DAA hip surgeons. METHODS:
      This study is a 1-year retrospective review of patients who underwent DAA total
      hip arthroplasty by 2 surgeons: one surgeon uses a flat table and manually
      elevates the femur with a large bone hook, while the other surgeon uses a
      fracture table and a mechanical femoral elevator. Exclusion criteria included
      cemented femoral implants, femoral neck fractures, and lack of 6-month follow-up.
      RESULTS: We identified 487 patients for analysis (220 male and 267 female,
      average age 66.55 years). There were 12 total IFFs (2.46%): 8 female and 4 male
      patients. The average age of IFF patients was 70.67 years and in nonfracture
      patients was 66.00 years. There was no difference in gender (P = .2981) or age (P
      = .2099) between IFF and nonfracture patients. In the fracture table group, there
      were 6 IFFs (2.22%) in 271 patients; in the nonfracture table group, there were 6
      IFFs (2.76%) in 216 patients. There was no statistical difference in IFF between
      the 2 groups (P = .6973). We observed just 2 patients (0.4%) in this series where
      the IFFs changed management requiring a revision femoral stem. CONCLUSION: There
      was no statistical difference in IFF with or without the use of fracture table.
      Both DAA surgical technique variations are felt to be equivalent regarding the
      risk for IFF during DAA cementless total hip arthroplasty.

PMID- 28511948
TI  - Computer Navigation Helps Reduce the Incidence of Noise After Ceramic-on-Ceramic
      Total Hip Arthroplasty.
AB  - BACKGROUND: Noise after ceramic-on-ceramic (CoC) total hip arthroplasty (THA) is
      a well-recognized problem. Computer navigation has been shown to achieve desired
      implant orientation. Our aim was (1) to compare the incidence of noise between
      navigated and conventional CoC THAs and (2) to determine the factors associated
      with noise. METHODS: All patients undergoing CoC THA between March 2009 and
      August 2012 were considered for this study. Information regarding hip noise was
      obtained via telephone or postal interview. A comparable cohort of patients in
      navigated and conventional groups was used to evaluate the incidence of noise.
      RESULTS: A total of 375 CoC THAs using the same implant (202 navigated and 173
      conventional) were evaluated. Patients <65 years of age had significantly greater
      incidence of noise (22.4% vs 6.1%; P < .001). To ensure similarity, a subgroup of
      cohort <65 years and a 32-mm head size was used to compare the incidence of noise
      between the navigated (68 THAs) and conventional (118 THAs) groups. Overall
      incidence of noise was significantly greater in the conventional group (28%) as
      compared with the navigated group (10%; P = .005). The relative risk of noise for
      the conventional vs the navigated group was 2.7 (P = .01), and for squeaking was
      1.9 (P = .2). Squeaking THAs had significantly lower cup anteversion (13.4
      degrees  +/- 5.2 degrees ) as compared with the silent THAs (17.6 degrees  +/-
      6.9 degrees ; P = .01). CONCLUSION: Navigated CoC THAs were 2.7* less likely to
      have noise as compared with the conventional ones. Squeaking THAs had
      significantly lower cup anteversion as compared with the silent ones. Patients of
      age <65 years had significantly greater incidence of noise after CoC THA.

PMID- 28511950
TI  - Benign Mullerian Inclusions in Lymphadenectomies for Renal Cell Carcinoma: A
      Radiologic and Pathologic Mimic of Metastases.

PMID- 28511949
TI  - Serum Metal Levels for Diagnosis of Adverse Local Tissue Reactions Secondary to
      Corrosion in Metal-on-Polyethylene Total Hip Arthroplasty.
AB  - BACKGROUND: Recently, corrosion at the head-neck junction in metal-on
      polyethylene bearing surface total hip arthroplasty (THA) has been recognized as
      a cause of adverse local tissue reactions (ALTRs). Serum metal levels have been
      advocated as a tool for the diagnosis of ALTR; however, no prior studies have
      specifically examined their utility. The purpose of this study was to determine
      the optimal cutoff values for serum cobalt and chromium levels in diagnosing ALTR
      after metal-on-polyethylene bearing surface THA. METHODS: We reviewed 447
      consecutive patients with serum metal levels tested at our institution and
      identified 64 patients with a metal-on-polyethylene bearing who had axial imaging
      or underwent reoperation to confirm the presence or absence of ALTR. Receiver
      operating characteristic curves were produced to identify cutoff thresholds to
      optimize sensitivity, and diagnostic test performance was characterized. RESULTS:
      Forty-four of the 64 patients (69%) were positive for an ALTR. The best test for
      the diagnosis of ALTR was the serum cobalt level (area under the curve [AUC] =
      99%). A threshold cutoff of >=1.0 ng/mL had a sensitivity of 100%, specificity of
      90%, positive predictive value (PPV) of 96%, and negative predictive value (NPV)
      of 100%. Serum chromium levels were also diagnostic (AUC = 87%). A threshold
      cutoff of >=0.15 ng/mL had a sensitivity of 100%, specificity of 50%, PPV of 81%,
      and NPV of 100%. Finally, serum cobalt-to-chromium ratio was also helpful for
      diagnosis (AUC = 90%). A threshold cutoff value of 1.4 for the cobalt-to-chromium
      ratio offered a sensitivity of 93%, specificity of 70%, PPV of 87%, and NPV of
      82%. CONCLUSION: Measurement of serum cobalt level with a threshold value of 1.0
      ng/mL in our experience is the best test for identifying the presence of ALTR in
      patients with a metal-on-polyethylene THA. Measurement of chromium level and the
      ratio of cobalt-to-chromium levels are also of value.

PMID- 28511952
TI  - Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and
      hippocampus of the adult rat brain.
AB  - Lithium an effective mood stabilizer, primary used in the treatment of bipolar
      disorders, has been reported as a protective agent in various neurological
      disorders. In this study, we examined the neuroprotective role of lithium
      chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of
      the adult rat brain. We determined that LiCl -attenuated LPS-induced activated
      toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear
      factor-kB (NF-KB) translation factor and various other inflammatory mediators
      such as interleukin-1 beta (IL-1beta) and tumour necrosis factor alpha (TNF
      alpha). We also analyzed that LiCl significantly abrogated activated gliosis via
      attenuation of specific markers for activated microglia, ionized calcium-binding
      adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP)
      in both the cortex and hippocampus of the adult rat brain. Furthermore, we also
      observed that LiCl treatment significantly ameliorated the increase expression
      level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase
      3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus
      regions of the LPS-treated adult rat brain. In addition, the morphological
      results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated
      the neuronal degeneration in the cortex and hippocampus regions of the LPS
      treated adult rat brain. Taken together, our Western blot and morphological
      results indicated that LiCl significantly prevents the LPS-induced neurotoxicity
      via attenuation of neuroinflammation and apoptotic neurodegeneration in the
      cortex and hippocampus of the adult rat brain.

PMID- 28511951
TI  - Proteome profiling reveals immune responses in Japanese flounder (Paralichthys
      olivaceus) infected with Edwardsiella tarda by iTRAQ analysis.
AB  - The liver is an important organ for bacterial pathogen attack in fish. The
      differential proteomic response of the Japanese flounder liver to Edwardsiella
      tarda infection was examined using isobaric tags for relative and absolute
      quantitation (iTRAQ) labeling followed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). A total of 3290 proteins were identified and classified
      into categories related to biological process (51.4%), molecular function
      (63.6%), and cellular component (57.7%). KEGG enrichment analysis indicated the
      complement and coagulation cascade pathways and the mineral absorption pathway
      were significantly enriched. Among the differentially expressed proteins, those
      involved in mediating complement cascade (e.g. complement component C7, C8, C9,
      complement factor H, complement factor Bf/C2) and mineral absorption (e.g.
      ferritin, STEAP-4) were most significantly upregulated during infection.
      Subsequently, five significantly upregulated (C4, C8beta, ferritin middle
      subunit, PRDX4-like and KRT18) and one significantly downregulated (transferrin)
      candidate immune proteins were validated by multiple reaction monitoring (MRM)
      assays. Furthermore, changes in expression of 15 proteins in the complement
      cascade and mineral absorption pathways were validated at the transcriptional
      level using quantitative real-time PCR (qPCR). The transcriptional levels of four
      transcription factors (p21Ras, Rab-31-like, NF-kappaB, STAT3) were also
      investigated by qPCR following infection with E. tarda. This study contributes to
      understanding the defense mechanisms of the liver in fish.

PMID- 28511954
TI  - High intensity interval training (HIIT) improves resting blood pressure,
      metabolic (MET) capacity and heart rate reserve without compromising cardiac
      function in sedentary aging men.
AB  - BACKGROUND: This study examined a programme of pre-conditioning exercise with
      subsequent high intensity interval training (HIIT) on blood pressure,
      echocardiography, cardiac strain mechanics and maximal metabolic (MET) capacity
      in sedentary (SED) aging men compared with age matched masters athletes (LEX).
      METHODS: Using a STROBE compliant observational design, 39 aging male
      participants (SED; n=22, aged 62.7+/-5.2yrs) (LEX; n=17, aged=61.1+/-5.4yrs) were
      recruited to a study that necessitated three distinct assessment phases;
      enrolment (Phase A), following pre-conditioning exercise in SED (Phase B), then
      following 6weeks of HIIT performed once every five days by both groups before
      reassessment (Phase C). Hemodynamic, echocardiographic and cardiac strain
      mechanics were obtained at rest and maximal cardiorespiratory and chronotropic
      responses were obtained at each measurement phase. RESULTS: The training
      intervention improved systolic, mean arterial blood pressure, rate pressure
      product and heart rate reserve (each P<0.05) in SED and increased MET capacity in
      both SED and LEX (P<0.01) which was amplified by HIIT. Echocardiography and
      cardiac strain measures were unremarkable apart from trivial increase to intra
      ventricular septum diastole (IVSd) (P<0.05) and decrease to left ventricular
      internal dimension diastole (LVId) (P<0.05) in LEX following HIIT. CONCLUSIONS: A
      programme of preconditioning exercise with HIIT induces clinically relevant
      improvements in blood pressure, rate pressure product and encourages recovery of
      heart rate reserve in SED, while improving maximal MET capacity in both SED and
      LEX without inducing any pathological cardiovascular remodeling. These data add
      to the emerging repute of HIIT as a safe and promising exercise prescription to
      improve cardiovascular function and metabolic capacity in sedentary aging.

PMID- 28511955
TI  - Chronic Diarrhea Caused by Chronic Lymphocytic Leukemia and Small Lymphocytic
      Lymphoma With Colorectal Involvement.

PMID- 28511953
TI  - Small conductance Ca2+-activated K+ channels in the plasma membrane, mitochondria
      and the ER: Pharmacology and implications in neuronal diseases.
AB  - Ca2+-activated K+ (KCa) channels regulate after-hyperpolarization in many types
      of neurons in the central and peripheral nervous system. Small conductance Ca2+
      activated K+ (KCa2/SK) channels, a subfamily of KCa channels, are widely
      expressed in the nervous system, and in the cardiovascular system. Voltage
      independent SK channels are activated by alterations in intracellular Ca2+
      ([Ca2+]i) which facilitates the opening of these channels through binding of Ca2+
      to calmodulin that is constitutively bound to the SK2 C-terminus. In neurons, SK
      channels regulate synaptic plasticity and [Ca2+]i homeostasis, and a number of
      recent studies elaborated on the emerging neuroprotective potential of SK channel
      activation in conditions of excitotoxicity and cerebral ischemia, as well as
      endoplasmic reticulum (ER) stress and oxidative cell death. Recently, SK channels
      were discovered in the inner mitochondrial membrane and in the membrane of the
      endoplasmic reticulum which sheds new light on the underlying molecular
      mechanisms and pathways involved in SK channel-mediated protective effects. In
      this review, we will discuss the protective properties of pharmacological SK
      channel modulation with particular emphasis on intracellularly located SK
      channels as potential therapeutic targets in paradigms of neuronal dysfunction.

PMID- 28511956
TI  - Erosion of the Duodenum by an Aortic Graft, Leading to Recurrent Sepsis.

PMID- 28511957
TI  - A stochastic vector-borne epidemic model: Quasi-stationarity and extinction.
AB  - We consider a stochastic model describing the spread of a vector borne disease in
      a community where individuals (hosts and vectors) die and new individuals (hosts
      and vectors) are born. The time to extinction of the disease, TQ, starting in
      quasi-stationary (conditional on non extinction) is studied. Properties of the
      limiting distribution are used to obtain an approximate expression for E(TQ), the
      mean-parameter in the exponential distribution of the time to extinction, for a
      finite population. It is then investigated numerically and by means of
      simulations how E(TQ) and its approximations depend on the different model
      parameters.

PMID- 28511958
TI  - Selection of discriminant mid-infrared wavenumbers by combining a naive Bayesian
      classifier and a genetic algorithm: Application to the evaluation of
      lignocellulosic biomass biodegradation.
AB  - Infrared spectroscopy provides useful information on the molecular compositions
      of biological systems related to molecular vibrations, overtones, and
      combinations of fundamental vibrations. Mid-infrared (MIR) spectroscopy is
      sensitive to organic and mineral components and has attracted growing interest in
      the development of biomarkers related to intrinsic characteristics of
      lignocellulose biomass. However, not all spectral information is valuable for
      biomarker construction or for applying analysis methods such as classification.
      Better processing and interpretation can be achieved by identifying
      discriminating wavenumbers. The selection of wavenumbers has been addressed
      through several variable- or feature-selection methods. Some of them have not
      been adapted for use in large data sets or are difficult to tune, and others
      require additional information, such as concentrations. This paper proposes a new
      approach by combining a naive Bayesian classifier with a genetic algorithm to
      identify discriminating spectral wavenumbers. The genetic algorithm uses a linear
      combination of an a posteriori probability and the Bayes error rate as the
      fitness function for optimization. Such a function allows the improvement of both
      the compactness and the separation of classes. This approach was tested to
      classify a small set of maize roots in soil according to their biodegradation
      process based on their MIR spectra. The results show that this optimization
      method allows better discrimination of the biodegradation process, compared with
      using the information of the entire MIR spectrum, the use of the spectral
      information at wavenumbers selected by a genetic algorithm based on a classical
      validity index or the use of the spectral information selected by combining a
      genetic algorithm with other methods, such as Linear Discriminant Analysis. The
      proposed method selects wavenumbers that correspond to principal vibrations of
      chemical functional groups of compounds that undergo degradation/conversion
      during the biodegradation of lignocellulosic biomass.

PMID- 28511959
TI  - Pattern formation in a nonlocal mathematical model for the multiple roles of the
      TGF-beta pathway in tumour dynamics.
AB  - The growth and invasion of cancer cells are very complex processes, which can be
      regulated by the cross-talk between various signalling pathways, or by single
      signalling pathways that can control multiple aspects of cell behaviour. TGF-beta
      is one of the most investigated signalling pathways in oncology, since it can
      regulate multiple aspects of cell behaviour: cell proliferation and apoptosis,
      cell-cell adhesion and epithelial-to-mesenchimal transition via loss of cell
      adhesion. In this study, we use a mathematical modelling approach to investigate
      the complex roles of TGF-beta signalling pathways on the inhibition and growth of
      tumours, as well as on the epithelial-to-mesenchimal transition involved in the
      metastasis of tumour cells. We show that the nonlocal mathematical model derived
      here to describe repulsive and adhesive cell-cell interactions can explain the
      formation of new tumour cell aggregations at positions in space that are further
      away from the main aggregation. Moreover, we show that the increase in cell-cell
      adhesion leads to fewer but larger aggregations, and the increase in TGF-beta
      molecules - whose late-stage effect is to decrease cell adhesion - leads to many
      small cellular aggregations. Finally, we perform a sensitivity analysis on some
      parameters associated with TGF-beta dynamics, and use it to investigate the
      relation between the tumour size and its metastatic spread.

PMID- 28511960
TI  - Inadequate target volume delineation and local-regional recurrence after
      intensity-modulated radiotherapy for human papillomavirus-positive oropharynx
      cancer.
AB  - PURPOSE: To perform a spatial analysis of local-regional recurrences, in relation
      to quantitative dose distribution, among patients treated by intensity-modulated
      radiotherapy (IMRT) for human papillomavirus (HPV)-positive oropharyngeal cancer.
      METHODS AND MATERIALS: The records of 107 consecutive patients who presented for
      consideration of re-irradiation for local-regional recurrent disease occurring in
      a previously irradiated field were reviewed. The original IMRT plans were
      retrieved for those with HPV-positive disease originating from the oropharynx,
      and deformable image registration was used to fuse the magnetic resonance imaging
      (MRI) and positron emission tomography (PET) scans obtained at recurrence to the
      pre-treatment planning computed tomography (CT) dataset. The recurrent tumor
      volume (Vrecur) was subsequently identified on axial imaging, and the dose of
      radiation received by Vrecur was then calculated and analyzed using dose-volume
      histograms. RESULTS: A total of 83 recurrent lesions occurring in 50
      oropharyngeal cancer patients were HPV-positive and met inclusion criteria. Using
      PET-defined Vrecur, thirty-three lesions were classified as in-field recurrences
      (40%), 35 were marginal misses (41%), and 15 were true misses (18%). Using the
      MRI-defined Vrecur, thirty-seven lesions were classified as in-field recurrences
      (45%), 32 were marginal misses (39%), and 14 were true misses (17%). CONCLUSION:
      A significant proportion of local-regional recurrences from HPV-positive
      oropharyngeal cancer represented geographical misses which possibly could have
      been prevented with more meticulous attention to IMRT planning. This finding has
      important implications with respect to ongoing attempts to de-escalate radiation
      dose for this disease. Our data highlight the importance of robust quality
      assurance with careful review of target volumes prior to the initiation of IMRT.

PMID- 28511961
TI  - Pre-Operative Evaluation of Axillary Lymph Node Status in Patients with Suspected
      Breast Cancer Using Shear Wave Elastography.
AB  - The aim of this study was to evaluate shear wave elastography (SWE) for pre
      operative evaluation of axillary lymph node (LN) status in patients with
      suspected breast cancer. A total of 130 axillary LNs in 130 patients who
      underwent SWE before fine-needle aspiration, core biopsy or surgery were
      analyzed. On gray-scale images, long and short axes, shape (elliptical or round),
      border (sharp or unsharp) and cortical thickening (concentric, eccentric or no
      fatty hilum) of LNs were assessed. On SWE, mean, maximum, minimum, standard
      deviation and the lesion-to-fat ratio (Eratio) values of elasticity were
      collected. Gray-scale and SWE features were compared statistically between
      metastatic and benign LNs using the chi2-test and independent t-test. Diagnostic
      performance of each feature was evaluated using the area under the receiver
      operating characteristic curve (AUC). Logistic regression analysis was used to
      determine gray-scale or SWE features independently associated with metastatic
      LNs. Of the 130 LNs, 65 (50%) were metastatic and 65 (50%) were benign after
      surgery. Metastatic LNs were significantly larger (p = 0.018); had higher
      elasticity indexes at SWE (p < 0.0001); and had higher proportions of round shape
      (p = 0.033), unsharp border (p = 0.048) and eccentric cortical thickening or no
      fatty hilum (p = 0.005) compared with benign LNs. On multivariate analysis,
      Eratio was independently associated with metastatic LNs (odds ratio = 3.312, p =
      0.008). Eratio had the highest AUC among gray-scale (0.582-0.719) and SWE (0.900
      0.950) variables. SWE had good diagnostic performance in metastatic axillary LNs,
      and Eratio was independently associated with metastatic LNs.

PMID- 28511962
TI  - Interventions for prevention of type 2 diabetes in relatives: A systematic
      review.
AB  - The relatives and partners of people with type 2 diabetes are at increased risk
      of developing type 2 diabetes. This systematic review examines randomized
      controlled trials, written in English that tested an intervention, which aimed to
      modify behaviors known to delay or prevent type 2 diabetes, among the relatives
      or partners of people with type 2 diabetes. Study quality was assessed using the
      Cochrane Collaboration's tool for assessing risk of bias. Seven studies met the
      inclusion criteria. The majority of studies were at low risk of bias. Six studies
      tested an intervention in first-degree relatives of people with type 2 diabetes
      and one in partners. Intervention components and intervention intensity across
      studies varied, with those targeting diet and physical activity reporting the
      most significant changes in primary outcomes. Only one study did not observe
      significant changes in primary outcomes. There were three main recruitment
      approaches: advertising in the community, recruiting people through their
      relatives with diabetes, or identifying people as high risk by screening of their
      own health care contacts. Some evidence was found for potentially successful
      interventions to prevent type 2 diabetes among the relatives and partners of
      people with type 2 diabetes, although finding simple and effective methods to
      identify and recruit them remains a challenge. Future studies should explore the
      effect of patients' perceptions on their family members' behavior and capitalize
      on family relationships in order to increase intervention effectiveness.

PMID- 28511964
TI  - Evidence on multimorbidity from definition to intervention: An overview of
      systematic reviews.
AB  - The increasing challenge of multiple chronic diseases (multimorbidity) requires
      more evidence-based knowledge and effective practice. In order to better
      understand the existing evidence on multimorbidity, we performed a systematic
      review of systematic reviews on multimorbidity with pre-established search
      strategies and exclusion criteria by searching multiple databases and grey
      literature. Of 8006 articles found, 53 systematic reviews (including meta
      analysis and qualitative research synthesis performed in some reviews) that
      stated multimorbidity as the main focus were included, with 79% published during
      2013-2016. Existing evidence on definition, measurement, prevalence, risk
      factors, health outcomes, clinical practice and medication (polypharmacy), and
      intervention and management were identified and synthesised. There were three
      major definitions from three perspectives. Seven studies on prevalence reported a
      range from 3.5% to 100%. As six studies showed, depression, hypertension,
      diabetes, arthritis, asthma, and osteoarthritis were prone to be comorbid with
      other conditions. Four groups of risk factors and eight multimorbidity associated
      outcomes were explored by five and six studies, respectively. Nine studies
      evaluated interventions, which could be categorized into either organizational or
      patient-oriented, the effects of these interventions were varied. Self-management
      process, priority setting and decision making in multimorbidity were synthesised
      by evidence from 4 qualitative systematic reviews. We were unable to draw solid
      conclusions from this overview due to the heterogeneity in methodology and
      inconsistent findings among included reviews. As suggested by all included
      studies, there is a need for prospective research, especially longitudinal cohort
      studies and randomized control trials, to provide more definitive evidence on
      multimorbidity.

PMID- 28511963
TI  - Short interfering RNA targeting Net1 reduces the angiogenesis and tumor growth of
      in vivo cervical squamous cell carcinoma through VEGF down-regulation.
AB  - Net1, a guanine nucleotide exchange factor, is implicated in cancer cell invasion
      through activation of RhoA. However, there is still no report on the association
      between Net1 and cancer angiogenesis. The current study was designed to explore
      the role of Net1 in the angiogenesis of cervical squamous cell carcinoma (CSCC)
      and further observe the effects of Net1 short interfering RNA (siRNA) on the
      tumor growth. Net1 was overexpressed in CSCC samples (n=80), correlated with the
      cancer microvessel density (r=0.223, P=.026), and related to aggressive clinical
      behaviors, including depth of cervical wall invasion (P=.041), parametrial
      involvement (P=.037), lymph node metastasis (P=.021), and vascular invasion
      (P=.018). Human umbilical vein endothelial cells treated with supernatant of SiHa
      cells with Net1 siRNA showed significantly decreased proliferation (0.75+/-0.038
      versus 1.0+/-0.015, P<.001), migration (39.3+/-6.5 versus 66.0+/-10.1, P=.019),
      and tube formation (13.5+/-3.05 versus 21.7+/-2.89, P=.030) compared with those
      human umbilical vein endothelial cells treated with normal SiHa cells
      supernatant. Net1 siRNA of SiHa decreased VEGF expression level (0.60+/-0.026
      versus 0.78+/-0.031, P=.02). Furthermore, Net1 siRNA significantly reduced tumor
      growth (P=.037) and microvessel density (5.8+/-0.43 versus 3.4+/-0.55, P=.012)
      and decreased the expression level of VEGF (0.31+/-0.002 versus 0.39+/-0.004,
      P<.001) in CSCC. In conclusion, Net1 promotes the angiogenesis of CSCC, and siRNA
      targeting Net1 can effectively reduce the angiogenesis and thus inhibit the tumor
      growth of CSCC in vivo.

PMID- 28511965
TI  - Relationship between hospital volume and outcomes in patients with traumatic
      brain injury: A retrospective observational study using a national inpatient
      database in Japan.
AB  - BACKGROUND: The relationship between hospital volume and outcome after traumatic
      brain injury (TBI) is not completely understood in a real clinical setting. We
      investigated whether patients admitted with TBI achieved better outcomes in high
      volume hospitals than in low-volume hospitals using a national inpatient database
      in Japan. METHODS: This retrospective cohort study used the Diagnosis Combination
      Procedure database in Japan. We included patients with TBI admitted to hospitals
      with a Japan Coma Scale (JCS) score >=2 between April 1, 2013 and March 31, 2014.
      Hospital volume was defined as the annual number of all admissions with TBI in
      individual hospitals. The hospital volume was categorized into four volume
      groups: low (<=60 admissions per hospital), medium-low (61-120 admissions per
      hospital), medium-high (121-180 admissions per hospital) and high (>=181
      admissions per hospital). The outcomes of interest included 28-day mortality and
      survival discharge with complete dependency defined as a Barthel Index score of 0
      at discharge. We used multivariate logistic regression models fitted with
      generalized estimating equations to evaluate relationships between the hospital
      volume and the outcomes. The hospital volume was evaluated both as categorical
      variables defined above and as continuous variables. RESULTS: The analysis
      dataset consisted of 20,146 eligible patients. Of these, 2,784 died within 28days
      (13.8%) and 3,409 were completely dependent among 16,996 patients discharged
      alive (20.1%). Multivariate analyses found that there was no significant
      difference between the high-volume and low-volume groups for 28-day mortality
      (adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.58-1.06 for the
      high-volume group) or complete dependency at discharge (adjusted OR 0.94, 95% CI
      0.71-1.23 for the high-volume group). The results were the same when the hospital
      volume was evaluated as a continuous variable. CONCLUSIONS: Hospital volume did
      not appear to influence outcomes in patients with TBI. High-volume hospitals may
      not be necessarily beneficial for patients with TBI exhibiting impaired
      consciousness as a whole.

PMID- 28511967
TI  - A sliding hip screw augmented with 2 screws is biomechanically similar to an
      inverted triad of cannulated screws in repair of a Pauwels type-III fracture.
AB  - OBJECTIVE: Pauwels III femoral neck fractures are highly unstable. These
      fractures are commonly treated with three cannulated screws or sliding hip screw
      (SHS) implants, however high rates of non-union persist. A hybrid SHS construct
      has recently been proposed. The objective of the study was to compare this
      construct to the familiar inverted triad of cannulated screws and to a single
      SHS. METHODS: Fourth generation biomechanical femur analogs were used to create a
      highly repeatable injury model. The hybrid SHS construct contained a SHS with two
      superior cannulated screws in an inverted triangle configuration. Eight samples
      for each construct were biomechanically evaluated and the results compared using
      ANOVA (p<0.05). RESULTS: The cannulated triad and hybrid SHS provided similar
      stiffness and fracture gap motion. The single SHS exhibited significantly lower
      stiffness and larger fracture plane diastasis than either the inverted triangle
      of cannulated screws or hybrid SHS (p<0.05). None of the constructs exhibited
      catastrophic failure during cyclic loading nor under loading up to 2.5 times body
      weight. CONCLUSIONS: The single SHS provided the least stable fracture fixation,
      while the inverted triad and hybrid SHS constructs were mechanically similar. The
      fracture repair simulated here illustrates how these repairs have the potential
      to return near pre-fracture strength in ideal conditions with young, healthy
      bone. However; in clinical situations where comminution impairs load transfer
      through the cortices the hybrid SHS may be the most favorable option.

PMID- 28511966
TI  - Identification of potential target genes and related regulatory transcription
      factors in spontaneous hairline fracture induced by hypervitaminosis A.
AB  - BACKGROUND: The aim was to research the molecular changes of bone cells induced
      by excessive dose of vitamin A, and analyze molecular mechanism underlying
      spontaneous fracture. METHODS: The gene expression profile of GSE29859, including
      4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control
      cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO)
      database. Differentially expressed genes (DGEs) between cortical bone marrow
      samples and control samples were screened out and pathway enrichment analysis was
      undertaken. Based on the MSigDB database, the potential regulatory transcription
      factors (TFs) were identified. RESULTS: A total of 373 DEGs including 342 up- and
      31 down-regulated genes were identified. These DEGs were significantly enriched
      in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated
      proteolysis and glycerophospholipid metabolism. Finally, the most significant
      regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA
      Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2
      (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). CONCLUSION: Key TFs
      including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1,
      Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by
      hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum,
      ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key
      mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our
      findings will provide new insights for the target selection in clinical
      application to prevent spontaneous fracture induced by hypervitaminosis A.

PMID- 28511968
TI  - The Future of Image-guided Radiotherapy.

PMID- 28511969
TI  - The current role of decompressive craniectomy for severe traumatic brain injury.
AB  - There is little doubt that decompressive craniectomy can reduce mortality
      however, the results of a recent study has provided more evidence to inform the
      debate regarding clinical and ethical concerns that it merely converts death into
      survival with severe disability or in a vegetative state. The recently published
      RESCUEicp trial compared last-tier secondary decompressive craniectomy with
      continued medical management for refractory intracranial hypertension after
      severe traumatic brain injury. Patients were randomly assigned to decompressive
      craniectomy with medical therapy or to receive continued medical therapy with the
      option of adding barbiturates. The results of the study support the findings of
      the stroke studies in that the reduction in mortality was almost directly
      translatable into survival with either severe disability or in a vegetative
      state. The question remains as to whether there is a subset of patients who
      obtain benefit from surgical decompression and it is in this regard that the use
      of observational cohort studies and sophisticated outcome prediction models may
      be of use. Comparing the percentage prediction with the observed long outcome
      provides an objective assessment of the most likely outcome can be obtained for
      patients thought to require surgical intervention. Whilst there will always be
      limitations when using this type of data they may help prompt appropriate patient
      centred discussions regarding realistic outcome expectations. A broader debate is
      also needed regarding use of a medical intervention that may leave a person in a
      condition that they may feel to be unacceptable and also places a considerable
      burden on society.

PMID- 28511970
TI  - Cleomedes of Astypalaea: A possible early sufferer of chronic traumatic
      encephalopathy.
AB  - Dementia pugilistica was the term adopted by H. Martland in 1928 to identify
      boxers with cognitive decline. In more recent years, the syndrome of dementia
      pugilistica with pathological correlates has been defined as chronic traumatic
      encephalopathy (CTE). A number of sportsmen have been recently diagnosed with
      CTE; and we may have identified an ancient Greek athlete of pankration who
      presented with the symptoms that have been associated with CTE. Our study reports
      the history and the known clinical information about Cleomedes of Astypalaea,
      possibly the first athlete ever affected by CTE.

PMID- 28511971
TI  - Learning curve for the endoscopic endonasal approach for suprasellar
      craniopharyngiomas.
AB  - The endoscopic endonasal approach is considered an alternative minimally invasive
      approach for suprasellar craniopharyngiomas. However, the complicated surgical
      manipulations required by this approach have limited its application. We evaluate
      whether the approach features a learning curve. Thirty-three patients were
      retrospectively reviewed and grouped as early (17 patients) and late (16 patient)
      groups. The operation time, extent of removal, ophthalmology, endocrinology,
      reconstruction and modifications of standard technique were evaluated. Between
      the two groups, the operation time decreased from 201.1+/-105.3min in the early
      group to 107.6+/-90.0min in the late group (p<0.05). Regarding clinical outcomes,
      non-significantly increasing trends toward the rate of gross total resection,
      visual improvement and (from 76.5% to 87.5%, 73.3% to 93.3%), significantly
      decreasing trends toward the rate of tumor recurrence (from 23.5% to 0% p<0.05)
      and non-significantly decreasing trends toward the rate of hypopituitarism
      recovery (26.7% to 0%) were observed between the two groups. With respect to
      complications, non-statistically significant decreasing trends toward transient
      cranial nerve paralysis (from 5.9% to 0%) and non-statistically significant
      increasing trends toward rate of CSF leakage, meningitis and new hypothyroidism
      (from 11.8% to 25%, 11.8% to 31.3%, 0 to 3%) were observed. We identified a
      learning curve for the endoscopic endonasal approach for suprasellar
      craniopharyngiomas. The exact number of patients necessary to establish a
      significant improvement in the clinical outcomes and decrease in the
      complications warrants further investigation. The outcomes of tumor recurrence
      may be associated with duration of follow-up. The CSF leakage represented the
      most common complication.

PMID- 28511972
TI  - A matched cohort comparison of cervical disc arthroplasty versus anterior
      cervical discectomy and fusion: Evaluating perioperative outcomes.
AB  - OBJECTIVE: Cervical disc arthroplasty (CDA) is a recent alternative to anterior
      cervical discectomy and fusion (ACDF) in patients suffering cervical disc
      herniation and degeneration. To date, a systematic analysis of their comparative
      advantages and risks following elective surgery remains elusive. METHODS: Adult
      patients undergoing elective CDA or ACDF were extracted from the American College
      of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database
      years 2011-2014. A total of 19,369 patients were matched 1:1 by age, sex,
      functional status, charlson comorbidity index, ASA classification, BMI
      classification, and number of vertebral levels operated on during surgery. This
      matching process led to a final sample of 588 subjects (294 CDA, 294 ACDF).
      Multivariable regression was performed for five outcome measures: operation time,
      early complications, reoperation rates, hospital length of stay (HLOS), and
      discharge destination. Mean differences (B), odds ratios (OR) and associated 95%
      confidence intervals (CI) are reported. RESULTS: Compared to ACDF, CDA was
      associated with decreased mean operation time (B=-18.78-min, 95% CI [-29.13, 
      8.42]; p<0.001), decreased HLOS (B=-0.44-days [-0.77, -0.11]; p=0.009), and
      increased likelihood of discharge to home (OR=5.39 [1.14-25.43]; p=0.033). No
      differences in reoperation rates and complications were found. CONCLUSION: In a
      matched cohort analysis, CDA performs comparably to ACDF and is associated with
      decreased operation time and HLOS, and increased likelihood of discharge to home,
      without differences in 30-day complications or reoperation rates. Future
      prospective studies are warranted.

PMID- 28511973
TI  - Anterior decompression and hybrid reconstruction with titanium mesh cage plus
      plate and self-locking stand-alone cage for the treatment of three-level cervical
      spondylotic myelopathy.
AB  - It has been reported that anterior cervical decompression has good clinical
      outcomes for the treatment of adjacent three-level cervical spondylotic
      myelopathy (CSM). However, the application of a long plate in the anterior
      cervical spine poses substantial risks of soft tissue damage. In this
      retrospective study, we aimed to analyze the clinical and radiological results of
      the hybrid construction with titanium mesh cage (TMC) plus plate and self-locking
      stand-alone cage for treatment of adjacent three-level CSM. A total of 28
      consecutive patients with adjacent three-level CSM were treated by anterior
      decompression and hybrid reconstruction with TMC plus plate and self-locking
      stand-alone cage. Clinical outcomes, complications, fusion rate and time, cage
      subsidence and spinal curvature were assessed. The mean follow-up period was
      22.8months. The average operative time was 103+/-18.5min, and the average blood
      loss was 115+/-13.3mL. The JOA score and degree of spinal curvature were
      significantly increased at the final follow-up compared with preoperatively
      (P<0.05). Twenty-seven cases finally achieved a solid fusion, and the average
      time to achieve a solid fusion was 6.2months. Postoperative complications
      included one case of cerebrospinal fluid leakage (3.57%), one case of temporary
      sore throat (3.57%) and two cases of TMC subsidence (7.1%). No dysphagia and
      hoarseness were observed. Anterior decompression and hybrid reconstruction with
      TMC plus plate and self-locking stand-alone cage could be used safely and
      effectively for the treatment of adjacent three-level CSM. It could effectively
      restore cervical lordosis, reduce the complications related to long plate
      fixation, and lead to satisfactory outcomes.

PMID- 28511974
TI  - Risk factor analysis for meralgia paresthetica: A hospital-based study in Taiwan.
AB  - Recognizing the cause is essential for the management of meralgia paresthetica
      (MP), also known as lateral femoral cutaneous neuropathy. The aim of this study
      was to investigate the etiologies of MP and their influence on each other. This
      retrospective study enrolled referral patients with electromyographic studies who
      fulfilled the clinical and electrodiagnostic criteria of MP from January 2003 to
      December 2013. Data including age, gender, body weight, body height, occupation,
      and relevant medical history were collected. The etiological analysis was based
      on age and gender. A total of 50 patients (30 males and 20 females) were
      enrolled. The average age (+/-standard deviation) at diagnosis was 49.8+/
      12.8years. Risk factors were identified in 29 cases (58.0%). More patients
      younger than 50years of age were male (73.1%, p=0.049). Peaks of age occurred
      between 41-50years in men and 51-60years in women. More males had a body mass
      index>=24kg/m2 (69.2% vs. 31.6%, p=0.012) and >=27kg/m2 (34.6% vs. 0.0%,
      p=0.006). Overweight and obese patients were more vulnerable to occupational
      factors (50.0% vs. 19.0%, p=0.030). Only one case had diabetes mellitus (2%).
      Male middle-aged patients with a higher body mass index and certain occupations
      had an increased risk of MP. In contrast to the peak age distribution of the male
      patients, the frequency of developing MP was relatively even among the women at
      all ages. The cause was often obscure.

PMID- 28511975
TI  - Leptomeningeal failure in patients with breast cancer receiving stereotactic
      radiosurgery for brain metastases.
AB  - PURPOSE: Prior studies suggest a high incidence of leptomeningeal failure (LMF)
      in breast cancer metastatic to brain. This study examines breast cancer-specific
      variables affecting development of LMF and survival after Gamma-Knife
      Radiosurgery (GKS). METHODS: Between 2000-2010, 149 (breast) and 658 other
      histology patients were treated with GKS. Hormone/HER2, age, local/distant brain
      failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were
      assessed. Median follow-up was 54months (range, 0-106). Serial MRI determined
      local and distant-brain failure and LMF. Statistical analysis with
      categorical/continuous data comparisons were done with Fisher's-exact, Wilcoxon
      rank-sum, log-rank tests, and Cox-Proportional Hazard models. RESULTS: Of 149
      patients, 21 (14%) developed LMF (median time of 11.9months). None of the
      following predicted for LMF: Her2-status (HR=0.49, p=0.16), hormone-receptor
      status (HR=1.15, p=0.79), prior craniotomy (HR=1.58, p=0.42), prior WBRT
      (HR=1.36, p=0.55). Non-significant factors between patients that did (n=21) and
      did not (n=106) develop LMF included neurologic death (p=0.34) and median
      survival (8.6 vs 14.2months, respectively). Breast patients who had distant
      failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2,
      p=0.005); including 15/65 (23%) patients who had distant-failure and developed
      LMF. Median time-to-death for patients experiencing LMF was 6.1months (IQR 3.4
      7.8) from onset of LMF. Median survival from LMF to death was much longer in
      breast (6.1months) than in other (1.7months) histologies CONCLUSION: Breast
      cancer patients had a longer survival after diagnosis of LMF versus other
      histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted
      for development of LMF in breast patients.

PMID- 28511976
TI  - Fertility, pregnancy, and prolactinoma: A survey of pituitary surgeons' view and
      review of the literature.
AB  - OBJECTIVE: Pituitary surgeons frequently encounter female prolactinoma patients
      seeking treatment to restore fertility. Current medical guidelines recommend
      using dopamine agonist (DA) for this, but for fetal safety, DA should stop upon
      pregnancy confirmation. The probability that prolactinoma may grow during
      pregnancy makes this last recommendation imperfect. With the advances in
      endoscopic surgery, we queried the potential role for surgery in these infertile
      patients, who may be ambivalent about both stopping and continuing DA while
      pregnant. METHODS: An anonymous survey was sent to pituitary surgeons to
      investigate how they would advise prolactinoma patients on treatment of
      infertility, and counsel them about pregnancy. Directories from various US-based
      neurosurgical societies were culled. Surgeons who designated themselves as "skull
      base"/"pituitary" were surveyed. RESULTS: Seventy-six surgeons responded (41%).
      The majority (67%) adhered to medical guidelines for microprolactinoma, but 26%
      recommended surgery. However, for a macroprolactinoma at diagnosis, the number of
      surgeons who recommended DA treatment vs. surgical treatment were almost evenly
      split (chi2p=0.06). The practice setting of a multidisciplinary clinic with
      endocrinologists did not significantly influence our respondents' choice. For a
      patient who presented after becoming pregnant on DA, our respondents were against
      surgery to prevent tumor growth (96%). CONCLUSION: A review of the current
      literature shows that both medical and surgical therapy have flaws. Significant
      numbers of surgeons considered surgery a legitimate option for prolactinoma
      patients seeking to be pregnant. The divergence between these surgeons' opinion
      and current medical guidelines warrants further investigation and discussion.

PMID- 28511977
TI  - Role of acetylcholine and serotonin in novelty processing using an oddball
      paradigm.
AB  - The processing of novel stimuli is known to take place in the hippocampus and
      frontal cortex, and is influenced by the cholinergic system. This ability is
      crucial to help detect changes in the environment and adapt behaviour
      accordingly. Previous research has shown that acetylcholine (ACh) can interact
      with serotonin (5-HT) at the hippocampal level, which may have consequences for
      cognitive functioning. However, little is known about the exact nature of this
      ACh and 5-HT interaction as well their possible interactive effects on novelty
      processing. We investigated the interactive role of ACh and 5-HT in novelty
      processing in healthy young participants. Levels of these neurotransmitters were
      manipulated with the muscarinic M1 antagonist biperiden, and with acute
      tryptophan depletion (ATD). Participants received either placebo, biperiden, ATD,
      or a combination of both in a double-blind cross-over design. Auditory event
      related potentials (ERPs) were recorded while a novelty oddball task was
      presented. Our results showed that biperiden affected ERP components considered
      to reflect attentional mechanisms; it increased the P50 amplitude and decreased
      that of the P200. Furthermore, a decrease of N100 amplitude by ATD was reversed
      by biperiden. The treatments did not affect the mismatch negativity (MMN)
      component, which is elicited when a deviant stimulus is presented in a sequence
      of repetitive stimuli. Importantly, biperiden decreased the amplitude of the ERP
      component related to novelty processing (P3a). The current study's results did
      not reveal an interactive effect of ACh and 5-HT on novelty processing. However,
      the data do suggest that ACh is involved in novelty processing and that it
      influences basic stimulus processing, without affecting sound-discrimination
      accuracy.

PMID- 28511978
TI  - Behavioural outcomes of adult female offspring following maternal stress and
      perinatal fluoxetine exposure.
AB  - : Depression, anxiety, and stress are common in pregnant women. One of the
      primary pharmacological treatments for anxiety and depression is the
      antidepressant fluoxetine (Flx). Maternal stress, depression, and Flx exposure
      are known to effect neurodevelopment of the offspring, however, their combined
      effects have been scarcely studied, especially in female offspring. The present
      study investigated the combined effects of maternal stress during pregnancy and
      perinatal exposure to Flx on the behaviour of female mice as adults. METHODS:
      Mouse dams were exposed to either chronic unpredictable stress (embryonic (E) day
      7 to E18), or FLX (E15- postnatal day 12), or a combination of stress and FLX or
      left untreated. At two months of age, the female offspring went through a
      comprehensive behavioural test battery. RESULTS: Maternal stress led to increased
      activity and alterations of prepulse inhibition in the adult female offspring.
      Maternal treatment with Flx had a potentially beneficial effect on spatial
      memory. The combination of prenatal stress and perinatal Flx exposure did not
      interact in their effects. These results suggest that gestational Flx exposure
      may have a limited negative impact on female offspring.

PMID- 28511979
TI  - Water and T-maze protocols are equally efficient methods to assess spatial memory
      in 3xTg Alzheimer's disease mice.
AB  - Rodent spatial memory is commonly tested using the water-maze; however, there is
      a potential confound of stress on learning in this behavioural paradigm. This is
      particularly relevant when testing spatial memory in models of neurodegeneration,
      such as the 3xTg mouse model for Alzheimer's disease. Here, we first confirmed
      that 3xTgAD mice express fear conditioning and then compared the performance of
      young and middle-aged mice on short-duration versions of the radial arm water
      maze (RAWM) and the minimally stressful T-maze spontaneous alternation task. Our
      main questions were: (1) does the reliance on stressors in water-maze training
      mask the true cognitive ability of 3xTgAD mice; and (2) are 3xTgAD mice similarly
      impaired in water-maze and T-maze protocols. Firstly, male and female 3xTgAD mice
      displayed intact freezing responses in both contextual and Pavlovian fear
      conditions. As male 3xTgAD mice displayed relatively enhanced fear responses the
      remaining tests were performed using only female 3xTgAD and control mice in order
      to equate for response to stressors. We found that alternation rates after both
      short and long delays were impaired at both ages in female 3xTgAD mice,
      indicative of robust spatial working memory deficits. For RAWM, again performance
      deficits were found in young 3xTgAD mice. As both tasks had similar efficacy at
      revealing early spatial memory deficits, we suggest that spontaneous behavioural
      protocols be prioritised over water maze testing in models such the 3xTgAD mouse
      as the former provide a far less stressful but equally effective alternative.

PMID- 28511980
TI  - Reward loss and the basolateral amygdala: A function in reward comparisons.
AB  - The neural circuitry underlying behavior in reward loss situations is poorly
      understood. We considered two such situations: reward devaluation (from large to
      small rewards) and reward omission (from large rewards to no rewards). There is
      evidence that the central nucleus of the amygdala (CeA) plays a role in the
      negative emotion accompanying reward loss. However, little is known about the
      function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA
      function in reward loss, negative emotion and reward comparisons, were tested in
      an experiment involving pretraining excitotoxic BLA lesions followed by training
      in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS)
      acquisition and extinction, anticipatory negative contrast (ANC), and open field
      testing (OF). Cell counts in the BLA (but not in the CeA) were significantly
      lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and
      accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF
      testing: higher activity in the periphery than in the central area. This pattern
      of results provides support for the hypothesis that BLA neurons are important for
      reward comparison. The three affected tasks (cSNC, ANC, and AS extinction)
      involve reward comparisons. However, ANC does not seem to involve negative
      emotions and it was affected, whereas OF activity is known to involve negative
      emotion, but it was not affected. It is hypothesized that a circuit involving the
      thalamus, insular cortex, and BLA is critically involved in the mechanism
      comparing current and expected rewards.

PMID- 28511981
TI  - Role of cholinergic receptors in memory retrieval depends on gender and age of
      memory.
AB  - The phenomenon of utilizing information acquired in the past to make decision and
      performance in present depends on memory retrieval, which is affected in
      retrograde amnesia. Role of cholinergic receptors in memory retrieval is not much
      explored. In this study we evaluated the gender specific role of cholinergic
      receptors, i.e. muscarinic and nicotinic receptors, in memory retrieval in young
      Balb/c mice. Acute (only one injection, 30min before test) and sub-chronic (five
      days) muscarinic blockade (using scopolamine=1mg/kg) before test impaired
      retrieval of contextual fear memory in male (31.45+/-5.39% and 33.36+/-3.78%
      respectively) and female mice (22.88+/-5.73%; P<0.05), except sub-chronically
      treated female group (33.31+/-4.90%; P>0.05). Only sub-chronic nicotinic receptor
      antagonism (using methyllycaconitine MLA=87.5MUg/kg and dihydro beta erythroidine
      DHbetaE=1mg/kg) in female showed significantly higher freezing response than
      control during contextual fear memory retrieval (60.85+/-7.71% and 40.91+/-7.53%
      respectively; P<0.001). Acute and sub-chronic muscarinic antagonism (but not
      nicotinic antagonism) impaired spatial memory retrieval in male (P<0.05) but not
      in female mice (P>0.05). There was no effect of acute and sub-chronic cholinergic
      receptor antagonism on discriminating novel object from the familiar one in male
      and female mice, however, nicotinic receptor blockade affected the working memory
      of all male and female mice on test day compared to the training sessions. Our
      results suggested that cholinergic receptors involvement in retrieving spatial
      and fear memories depends on the age of the memory and gender.

PMID- 28511983
TI  - Target temperature management after cardiac arrest in comatose survivors in
      Brazil - A survey of the current clinical practice.

PMID- 28511982
TI  - Characteristic and intermingled neocortical circuits encode different visual
      object discriminations.
AB  - Synaptic plasticity and neural network theories hypothesize that the essential
      information for advanced cognitive tasks is encoded in specific circuits and
      neurons within distributed neocortical networks. However, these circuits are
      incompletely characterized, and we do not know if a specific discrimination is
      encoded in characteristic circuits among multiple animals. Here, we determined
      the spatial distribution of active neurons for a circuit that encodes some of the
      essential information for a cognitive task. We genetically activated protein
      kinase C pathways in several hundred spatially-grouped glutamatergic and
      GABAergic neurons in rat postrhinal cortex, a multimodal associative area that is
      part of a distributed circuit that encodes visual object discriminations. We
      previously established that this intervention enhances accuracy for specific
      discriminations. Moreover, the genetically-modified, local circuit in POR cortex
      encodes some of the essential information, and this local circuit is
      preferentially activated during performance, as shown by activity-dependent gene
      imaging. Here, we mapped the positions of the active neurons, which revealed that
      two image sets are encoded in characteristic and different circuits. While
      characteristic circuits are known to process sensory information, in sensory
      areas, this is the first demonstration that characteristic circuits encode
      specific discriminations, in a multimodal associative area. Further, the circuits
      encoding the two image sets are intermingled, and likely overlapping, enabling
      efficient encoding. Consistent with reconsolidation theories, intermingled and
      overlapping encoding could facilitate formation of associations between related
      discriminations, including visually similar discriminations or discriminations
      learned at the same time or place.

PMID- 28511985
TI  - Reply to: Time matters in patients undergoing extracorporeal cardiopulmonary
      resuscitation.

PMID- 28511984
TI  - Comparison of three cognitive exams in cardiac arrest survivors.
AB  - BACKGROUND: Cognitive deficits may detract from quality of life after cardiac
      arrest. Their pattern and prevalence are not well documented. We used the
      Computer Assessment of Mild Cognitive Impairment (CAMCI), the Montreal Cognitive
      Assessment (MOCA) and the 41 Cent Test (41CT) to assess cognitive impairment in
      cardiac arrest survivors and examine the exams' diagnostic accuracy. We
      hypothesized that the scores of these exams would indicate the presence of
      cognitive impairment in arrest survivors, that the overall scores on the three
      study assessments would correlate with one another, and that the 41CT, MOCA, and
      executive function element of the CAMCI would vary independently from other non
      executive CAMCI components, reflecting executive function impairment after
      cardiac arrest. METHODS: Four researchers administered the CAMCI, MOCA, and/or
      the 41CT to cardiac arrest survivors after discharge from the intensive care unit
      between 2010 and 2015. Physicians screened patients with the Mini-Mental State
      Exam to determine when this cognitive testing was feasible, generally when the
      patient was able to score 20-25 points on the MMSE. We performed pairwise
      correlations between the different subscales' and tests' scores. RESULTS: One
      hundred and fourteen participants completed the CAMCI, of which 38 (33.3%)
      participants additionally completed the MOCA and 41CT. The median (IQR)
      percentile score for CAMCI for all 114 participants was 33.5 (18.3, 49.8), which
      corresponds to moderately low risk of impairment. The median (IQR) for the MOCA
      was 22.0 (19, 24.8) out of a possible 30, which is considered indicative of
      abnormal cognitive function, and for the 41CT was 6 (5, 7) out of a possible 7
      points when all 38 participants were included. MOCA correlated strongly with the
      overall CAMCI score (r=0.71); the CAMCI correlated moderately strongly with the
      41CT (r=0.62) and the MOCA and 41CT were moderately strongly correlated with each
      other (r=0.56). When all 114 CAMCI scores were considered, the Executive Accuracy
      subscale was strongly correlated with the overall CAMCI score (r=0.81).
      CONCLUSION: The CAMCI detects cognitive impairment after cardiac arrest. The MOCA
      correlates strongly with the overall CAMCI and the executive function subscale of
      the CAMCI. The 41CT as appears less effective than the MOCA in detecting
      cognitive deficits.

PMID- 28511987
TI  - Human parechovirus type 3 infection: An emerging infection in neonates and young
      infants.
AB  - Human parechoviruses (HPeVs) are RNA viruses that have characteristics similar to
      those of enteroviruses and usually cause mild respiratory or gastrointestinal
      symptoms. Human parechovirus type 3 (HPeV3), first reported in 2004, is
      exceptional because it can provoke sepsis and meningoencephalitis leading to
      neurological sequelae, and even death, in neonates and young infants.
      Pediatricians and researchers are increasingly aware that HPeV3 is responsible
      for serious disease in neonates and young infants. Retrospective studies and
      several reports of epidemics of HPeV3 infection have provided data on
      epidemiology, clinical symptoms and signs, laboratory findings, and outcomes.
      However, the pathogenesis of HPeV3 infection remains unclear, which explains the
      lack of specific antiviral therapy and effective prevention measures. Maternal
      antibodies are important in protection against severe HPeV3-related disease, and
      this may be a clue regarding its pathogenesis. HPeV3 epidemics are likely to
      continue, and because the clinical manifestations of HPeV3 are severe,
      determining the pathogenesis of HPeV3 infection and establishing specific
      antiviral therapies are important goals for future research.

PMID- 28511986
TI  - Epileptiform discharge detection with the 4-channel frontal
      electroencephalography during post-resuscitation care.
AB  - INTRODUCTION: We performed this study to investigate whether the SEDline system,
      a 4-channel-processed electroencephalography (EEG) monitoring device in the
      frontal area, can detect epileptiform discharges accurately during post
      resuscitation care in comatose cardiac arrest survivors. METHODS: Adult comatose
      cardiac arrest survivors, who were admitted to the intensive care unit (ICU) for
      post-resuscitation care including TTM, were enrolled. Within 72h post-return of
      spontaneous circulation (ROSC), conventional EEG was conducted for 30min. The
      SEDline system data were recorded with a video camera simultaneously with
      conventional EEG. Data retrieved from conventional EEG were interpreted by a
      neurologist and data from the SEDline system were interpreted by three emergency
      physicians blinded to the conventional EEG data. Then, the sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      and accuracy of the SEDline system to detect epileptiform discharges were
      calculated. RESULTS: Thirty-nine patients were enrolled in this study.
      Epileptiform discharges were confirmed in 6 patients (15.4%) who had the same
      patterns of generalized periodic epileptiform discharges in both conventional EEG
      and the concurrent SEDline system. The SEDline system showed 100.0% (95%
      confidence interval (CI), 54.1-100.0%) of sensitivity, 100.0% (95% CI, 89.4
      100.0%) of specificity, 100.0% (95% CI, 54.1-100.0%) of PPV, and 100.0% (95% CI,
      89.4-100.0%) of NPV. The overall classification accuracy of the SEDline system to
      detect epileptiform discharges was 100.0%. CONCLUSION: The SEDline system
      detected epileptiform discharges accurately in comatose cardiac arrest survivors
      during post-resuscitation care.

PMID- 28511988
TI  - Exploring the Potential of Nanotherapeutics in Targeting Tumor Microenvironment
      for Cancer Therapy.
AB  - Advanced research in the field of cancer biology clearly demonstrated the key
      role of tumor microenvironment (TME) in cancer development and metastasis
      particularly in solid tumors. Components of TME, being non-neoplastic in nature
      provide supportive and permissive conditions for the growth of cancer cells.
      Hence it is important to modify TME in cancer therapy and this would be achieved
      by better understanding of TME morphological features and functioning of stromal
      components. Nanotechnology based drug delivery offers various advantages such as
      prolonged circulation time, delivery of cargo at desired site, improved
      bioavailability, reduced toxicity etc. over conventional chemotherapeutics.
      Abnormal characteristic features of TME play a paradoxical role in
      nanoparticulate drug delivery. Leaky vasculature, acidic and hypoxic conditions
      of TME helps in the accumulation of tailored nanoparticles whereas high
      interstitial pressure and dense stroma restrict the extravasation, homogenous
      distribution of nanocarriers in TME. This review mainly discusses the potential
      of nanotherapeutics in targeting TME by briefly discussing stromal components,
      therapeutic opportunities and barriers offered by TME for nanoparticulate drug
      delivery. Updated information on TME remodeling strategies for improved drug
      delivery and specific targeting of individual stromal components are also
      outlined.

PMID- 28511990
TI  - Corrigendum to "Inhibition of autophagy enhances hydroquinone-induced TK6 cell
      death" [Toxicol. in Vitro 41 (2017) 123-132].

PMID- 28511989
TI  - Biased agonism/antagonism at the AngII-AT1 receptor: Implications for adrenal
      aldosterone production and cardiovascular therapy.
AB  - Many of the effects of angiotensin II (AngII), including adrenocortical
      aldosterone release, are mediated by the AngII type 1 receptor (AT1R), a receptor
      with essential roles in cardiovascular homeostasis. AT1R belongs to the G protein
      coupled receptor (GPCR) superfamily, mainly coupling to the Gq/11 type of G
      proteins. However, it also signals through betaarrestins, oftentimes in parallel
      to eliciting G protein-dependent signaling. This has spurred infinite
      possibilities for cardiovascular pharmacology, since various beneficial effects
      are purportedly exerted by AT1R via betaarrestins, unlike AT1R-induced G protein
      mediated pathways that usually result in damaging cardiovascular effects,
      including hypertension and aldosterone elevation. Over the past decade however, a
      number of studies from our group and others have suggested that AT1R-induced
      betaarrestin signaling can also be damaging for the heart, similarly to the G
      protein-dependent one, with regard to aldosterone regulation. Additionally, AT1R
      induced betaarrestin signaling in astrocytes from certain areas of the brain may
      also play a significant role in central regulation of blood pressure and
      hypertension pathogenesis. These findings have provided the impetus for testing
      available angiotensin receptor blockers (ARBs) in their efficacy towards blocking
      both routes (i.e. both G protein- and betaarrestin-dependent) of AT1R signaling
      in vitro and in vivo and also have promoted structure-activity relationship (SAR)
      studies for the AngII molecule in terms of betaarrestin signaling to certain
      cellular effects, e.g. adrenal aldosterone production. In the present review, we
      will recount all of these recent studies on adrenal and astrocyte AT1R-dependent
      betaarrestin signaling while underlining their implications for cardiovascular
      pathophysiology and therapy.

PMID- 28511991
TI  - Calculation of the cross-sectional shape of a fibril from equatorial scattering.
AB  - An alternate formulation of helical diffraction theory is used to generate cross
      sectional shapes of fibrous structures from equatorial scattering. We demonstrate
      this approach with computationally generated scattering intensities and then
      apply it to scattering data from Tobacco Mosaic Virus (TMV) and in vitro
      assembled fibrils of Abeta40 peptides. Refining the cross-sectional shape of TMV
      from SAXS data collected on a 26mg/ml solution resulted in a circular shape with
      outer diameter of ~180A and inner diameter of ~40A consistent with the known
      structure of TMV. We also utilized this method to analyze the equatorial
      scattering from TMV collected by Don Caspar from a concentrated (24% ~295mg/ml)
      gel of TMV as reported in his Ph.D. thesis in 1955. This data differs from the
      SAXS data in having a sharp interference peak at ~250A spacing, indicative of
      strong interparticle interactions in the gel. Analysis of this data required
      consideration of interatomic vectors as long as 2000A and resulted in generation
      of images that were interpreted as representative of local organization of TMV
      particles in the sample. Peaks in the images were separated, on average by about
      250A with a density consistent with Caspar's original measurements. Analysis of
      SAXS data from Abeta fibrils resulted in a cross-sectional shape that could be
      interpreted in terms of structural models that have been constructed from ssNMR
      and cryoEM. These results demonstrate an unexpected use of the small-angle region
      of fiber diffraction patterns to derive fundamental structural properties of
      scattering objects.

PMID- 28511992
TI  - RNA-seq analyses reveal that cervical spinal cords and anterior motor neurons
      from amyotrophic lateral sclerosis subjects show reduced expression of
      mitochondrial DNA-encoded respiratory genes, and rhTFAM may correct this
      respiratory deficiency.
AB  - Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative
      disease of adults that produces weakness and atrophy due to dysfunction and death
      of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze
      expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and
      CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed
      with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to
      recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3
      dimensions clustered gene networks activated by rhTFAM, quantitated their
      interactions with other genes and determined their gene ontology (GO) families.
      RNA-seq and quantitative PCR (qPCR) analyses showed reduced mitochondrial gene
      expression in ALS hCSC and ALS motor neurons isolated by laser capture
      microdissection (LCM), and revealed that hNSC and CTL human cervical spinal cords
      were similar. Rats treated with i.v. rhTFAM showed a dose-response increase in
      brain respiration and an increase in spinal cord mitochondrial gene expression.
      Treatment of hNSC with rhTFAM increased expression of mtDNA-encoded respiratory
      genes and produced one major and several minor clusters of gene interactions.
      Gene ontology (GO) analysis of rhTFAM-stimulated gene clusters revealed
      enrichment in GO families involved in RNA and mRNA metabolism, suggesting
      mitochondrial-nuclear signaling. In postmortem ALS hCSC and LCM-isolated motor
      neurons we found reduced expression of mtDNA respiratory genes. In hNSC's rhTFAM
      increased mtDNA gene expression and stimulated mRNA metabolism by unclear
      mechanisms. rhTFAM may be useful in improving bioenergetic function in ALS.

PMID- 28511993
TI  - The expression of opioid genes in non-classical reward areas depends on early
      life conditions and ethanol intake.
AB  - The young brain is highly sensitive to environmental influences that can cause
      long-term changes in neuronal function, possibly through altered gene expression.
      The endogenous opioid system continues to mature after birth and because of its
      involvement in reward, an inadequate maturation of this system could lead to
      enhanced susceptibility for alcohol use disorder. Recent studies show that the
      classical reward areas nucleus accumbens and ventral tegmental area are less
      affected by early life stress whereas endogenous opioids in non-classical areas,
      e.g. dorsal striatum and amygdala, are highly responsive. The aim was to
      investigate the interaction between early life conditions and adult voluntary
      ethanol intake on opioid gene expression. Male Wistar rats were exposed to
      conventional rearing, 15, or 360min of daily maternal separation (MS) postnatal
      day 1-21, and randomly assigned to ethanol or water drinking postnatal week 10
      16. Rats exposed to early life stress (MS360) had increased opioid receptor gene
      (Oprm1, Oprd1 and Oprk1) expression in the dorsal striatum. Ethanol drinking was
      associated with lower striatal Oprd1 and Oprk1 expression solely in rats exposed
      to early life stress. Furthermore, rats exposed to early life stress had high
      inherent Pomc expression in the amygdala but low expression after ethanol intake.
      Thus, adverse events early in life induced changes in opioid gene expression and
      also influenced the central molecular response to ethanol intake. These long-term
      consequences of early life stress can contribute to the enhanced risk for
      excessive ethanol intake and alcohol use disorder seen after exposure to
      childhood adversity.

PMID- 28511994
TI  - Study of rubella candidate vaccine based on a structurally modified plant virus.
AB  - A novel rubella candidate vaccine based on a structurally modified plant virus -
      spherical particles (SPs) - was developed. SPs generated by the thermal
      remodelling of the tobacco mosaic virus are promising platforms for the
      development of vaccines. SPs combine unique properties: biosafety, stability,
      high immunogenicity and the effective adsorption of antigens. We assembled in
      vitro and characterised complexes (candidate vaccine) based on SPs and the
      rubella virus recombinant antigen. The candidate vaccine induced a strong humoral
      immune response against rubella. The IgG isotypes ratio indicated the
      predominance of IgG1 which plays a key role in immunity to natural rubella
      infection. The immune response was generally directed against the rubella antigen
      within the complexes. We suggest that SPs can act as a platform (depot) for the
      rubella antigen, enhancing specific immune response. Our results demonstrate that
      SPs-antigen complexes can be an effective and safe candidate vaccine against
      rubella.

PMID- 28511995
TI  - Live, full-term mouse pups from oocytes grown and matured in vitro with serum
      substitutes.
AB  - For in vitro growth and maturation of mouse oocytes (IVG-IVM), serum is added to
      media up to and including the stage of oocyte maturation; this subsequently
      supports oocytes through fertilization and early embryo development. However,
      problems may occur with sera, such as batch differences and issues of biosafety.
      The purpose of the present study was to determine the capacity for fertilization
      and pre- and post-implantation development of oocytes that underwent IVG-IVM with
      a serum substitute. Oocyte-granulosa cell complexes from preantral follicles were
      cultured in medium with either fetal bovine serum (FBS), Serum Substitute
      SupplementTM (SSS), or KnockoutTM Serum Replacement (KSR) for 10days, and were
      then allowed to mature for 17 h. Subsequently, more than 90% of oocytes underwent
      germinal vesicle breakdown (GVBD) and more than 70% reached metaphase II, with no
      significant difference between the groups. A lower fertilization rate, presumably
      due to zona hardening, was found in the serum substitute groups. Nevertheless,
      more than 50% of the inseminated oocytes were fertilized and 35%-45% of them
      underwent first cleavage and developed to the blastocyst stage. Following embryo
      transfer, one and four live offspring were produced from the SSS and KSR groups,
      respectively. The present study demonstrated that murine IVG-IVM oocytes cultured
      in media with a serum substitute, achieved fertilization in vitro, pre- and post
      implantation development, and the delivery of live pups, although the efficiency
      of the process is reduced compared to FBS supplementation.

PMID- 28511996
TI  - Comparative characteristics of spermatozoa harvested and cryopreserved in culture
      and cryoprotectant media with or without donor serum proteins.
AB  - The objectives of this study is to evaluate the efficacy of protein-free media in
      the preparation, holding and crypreservation of spermatazoa for use in ART.
      Normozoospermic semen samples (N=71) were used to compare the effects of media on
      the survival and quality of spermatozoa when washed and cultured with different
      media with and without added proteins at 4 degrees C, 15 degrees C, 22 degrees C
      and 37 degrees C for 0, 4-7 and 24h. Survival and quality of spermatozoa were
      assessed after freeze-thaw with synthetic cryoprotectant with and without
      proteins. Ethics/IRB approval was obtained (Ref. 1073.52). Spermatozoa parameters
      were similar in all media after washing and culture for 24h. Post-thaw survival
      and quality of spermatozoa was not significantly different 24h after thawing of
      samples frozen in all cryoprotectant medium. In conclusion synthetic protein-free
      culture and cryoprotectant media are equal in efficacy to protein-containing
      media in culture and cryopreservation of spermatozoa . Use of these synthetic
      media are anticipated to significantly reduce the risk, potentially associated
      with conventional protein-containing media, of transmission of disease and
      possibly harmful undeclared proteins to the patient, baby and the healtcare
      worker. Synthetic media also ensure consistency of quality between batches of
      media.

PMID- 28511997
TI  - Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving
      cardiac safety testing paradigm.
AB  - Since 2005, when the International Conference on Harmonisation (ICH) E14
      guideline was adopted, no drug has been withdrawn because of QTc prolongation or
      torsade de pointes arrhythmia. There are, however, costs associated with this
      success. In addition to the time and money invested, thorough QT (TQT) studies
      have limited the efficiency of the drug development pipeline. In this paper, we
      discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction
      as a part of the debate regarding their usefulness.

PMID- 28511999
TI  - Clinical nutrition education in medical schools: Results of an ESPEN survey.

PMID- 28511998
TI  - A J-shaped association between soy food intake and depressive symptoms in Chinese
      adults.
AB  - BACKGROUND & AIMS: Soy food has been proven to have multiple positive effects on
      human health, however, no study has yet investigated the association between
      habitual intake of soy food and depressive symptoms in general population. The
      objective of this study was to examine this association. METHODS: In a cross
      sectional analysis, we studied a sample of 13,760 adults (mean age 43.5 years) in
      Tianjin, China. The Self-Rating Depression Scale (SDS) was used to assess
      depressive symptoms, with four cut-off points (SDS >=40, 45, 48 or 50) indicating
      increased level of depressive symptoms. Food Frequency Questionnaire (FFQ) was
      used to assess dietary intake. RESULTS: In the total population, the prevalence
      of increased depressive symptoms was 7.2% (SDS >=50). Comparing to the group with
      lowest intake frequency of soy food (<once/week), the fully adjusted odds ratios
      (95% confidence intervals) of depressive symptoms were 0.80 (0.67, 0.95) for 1-3
      times/week, 0.69 (0.55, 0.86) for 4-7 times/week, and 1.85 (1.21, 2.80) for
      >=twice/day. Associations remained when other cut-off points (SDS >=40, 45 or 48)
      were used as a definition of increased depressive symptoms. CONCLUSION: Findings
      from this study suggested a J-shaped association between intake frequency of soy
      food and incidence of depressive symptoms among adults. For the first time, the
      study provides evidence that light-to-moderate intake of soy food may reduce the
      incidence of depressive symptoms, while relatively high (>=twice/day) intake may
      generate the opposite effect.

PMID- 28512000
TI  - Computed tomography (CT)-compatible remote center of motion needle steering
      robot: Fusing CT images and electromagnetic sensor data.
AB  - Lung cancer is the most common cause of cancer-related death, and early detection
      can reduce the mortality rate. Patients with lung nodules greater than 10 mm
      usually undergo a computed tomography (CT)-guided biopsy. However, aligning the
      needle with the target is difficult and the needle tends to deflect from a
      straight path. In this work, we present a CT-compatible robotic system, which can
      both position the needle at the puncture point and also insert and rotate the
      needle. The robot has a remote-center-of-motion arm which is achieved through a
      parallel mechanism. A new needle steering scheme is also developed where CT
      images are fused with electromagnetic (EM) sensor data using an unscented Kalman
      filter. The data fusion allows us to steer the needle using the real-time EM
      tracker data. The robot design and the steering scheme are validated using three
      experimental cases. Experimental Case I and II evaluate the accuracy and CT
      compatibility of the robot arm, respectively. In experimental Case III, the
      needle is steered towards 5 real targets embedded in an anthropomorphic gelatin
      phantom of the thorax. The mean targeting error for the 5 experiments is 1.78 +/-
      0.70 mm. The proposed robotic system is shown to be CT-compatible with low
      targeting error. Small nodule size and large needle diameter are two risk factors
      that can lead to complications in lung biopsy. Our results suggest that nodules
      larger than 5 mm in diameter can be targeted using our method which may result in
      lower complication rate.

PMID- 28512003
TI  - Towards a sustainable biobased industry - Highlighting the impact of
      extremophiles.
AB  - The transition of the oil-based economy towards a sustainable economy completely
      relying on biomass as renewable feedstock requires the concerted action of
      academia, industry, politics and civil society. An interdisciplinary approach of
      various fields such as microbiology, molecular biology, chemistry, genetics,
      chemical engineering and agriculture in addition to cross-sectional technologies
      such as economy, logistics and digitalization is necessary to meet the future
      global challenges. The genomic era has contributed significantly to the
      exploitation of natures biodiversity also from extreme habitats. By applying
      modern technologies it is now feasible to deliver robust enzymes (extremozymes)
      and robust microbial systems that are active at temperatures up to 120 degrees C,
      at pH 0 and 12 and at 1000bar. In the post-genomic era, different sophisticated
      "omics" analyses will allow the identification of countless novel enzymes
      regardless of the lack of cultivability of most microorganisms. Furthermore,
      elaborate protein-engineering methods are clearing the way towards tailor-made
      robust biocatalysts. Applying environmentally friendly and efficient biological
      processes, terrestrial and marine biomass can be converted to high value products
      e.g. chemicals, building blocks, biomaterials, pharmaceuticals, food, feed and
      biofuels. Thus, further application of extremophiles has the potential to improve
      sustainability of existing biotechnological processes towards a greener biobased
      industry.

PMID- 28512005
TI  - Intraosseous venous drainage anomaly at the tibia.

PMID- 28512001
TI  - Low dose inflammatory potential of silica particles in human-derived THP-1
      macrophage cell culture studies - Mechanism and effects of particle size and
      iron.
AB  - Silica and iron are major constituents in ambient particulate matter, and iron is
      a common impurity in many engineered nanomaterials. The purpose of this work was
      to determine the pro-inflammatory and other biological effects and mechanism of
      particle size and iron presence under low dose, non-cytotoxic conditions that are
      likely to approximate actual exposure levels, in contrast with higher dose
      studies in which cytotoxicity occurs. Specifically, human-derived THP-1
      macrophages were exposed to 1 MUg/ml of pristine and iron-coated 50 nm and 2 MUm
      engineered silica nanoparticles. Particles were first characterized for size,
      size distribution, surface area, iron concentration, phase and aggregation in
      cell culture media. Then, biological assays were conducted to determine a non
      lethal dose used in subsequent experiments. Superoxide production, lipid
      peroxidation, and increased pro-inflammatory cytokine (TNF-alpha and IL-1beta)
      mRNA expression were measured as a function of particle size and iron presence.
      Smaller particle size and the presence of iron increased superoxide production,
      lipid peroxidation, and the induction of pro-inflammatory cytokine mRNA
      expression. Separate addition of an iron-chelator, a scavenger of superoxide and
      hydrogen peroxide, and an inhibitor of phosphatidylcholine specific phospholipase
      C (PC-PLC), suppressed the increase in cytokine mRNA expression. Furthermore,
      free iron itself showed none of the aforementioned effects. The results highlight
      the importance of particle size and iron in lung inflammation for both natural
      and engineered nanomaterials, under low dose, non-toxic conditions, and support
      the role of an oxidant, lipid peroxidation and PC-PLC dependent inflammatory
      mechanism.

PMID- 28512006
TI  - Stress fracture in athletes.
AB  - Stress fractures are widely encountered in sport medicine and rheumatology.
      Stress fractures result from abnormal and repetitive loading on normal bone that
      lead to microdamage and then fracture. They occur after sudden increase in
      physical activity. They appear mostly at lower limbs. Women are at higher risk
      than men. Patients complain of mechanical pain. Clinical findings include focused
      pain and sometimes swelling. No biological test is useful for diagnosis. Plain
      radiographs are normal in early stage disease. MRI is the gold standard to
      confirm stress fracture. Treatments of stress fracture always involve rest and
      analgesics. Non-steroidal anti-inflammatory should be use cautiously because they
      may inhibit callus formation. Extracorporeal shockwave may be a new approach for
      SF not healing with rest. Surgical treatment is often needed in high risk stress
      fracture of delayed healing, non-union or complete fracture.

PMID- 28512002
TI  - Cell-surface G-protein-coupled receptors for tumor-associated metabolites: A
      direct link to mitochondrial dysfunction in cancer.
AB  - Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative
      phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of
      mitochondrial function is one of the most significant changes that occurs in
      tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and
      epigenetics. In particular, three mitochondrial enzymes are inactivated in
      cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3
      hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to
      regulation via acetylation/deacetylation. SIRT3, the predominant mitochondrial
      deacetylase, directly targets these enzymes for deacetylation and maintains their
      optimal catalytic activity. SIRT3 is a tumor suppressor, and deacetylation of
      these enzymes contributes to its biological function. PDH catalyzes the oxidative
      decarboxylation of pyruvate into acetyl CoA, SDH oxidizes succinate into
      fumarate, and HMGCS2 controls the synthesis of the ketone body beta
      hydroxybutyrate. As the activities of these enzymes are decreased in cancer,
      tumor cells accumulate lactate and succinate but produce less amounts of beta
      hydroxybutyrate. Apart from their role in cellular energetics, these metabolites
      function as signaling molecules via specific cell-surface G-protein-coupled
      receptors. Lactate signals via GPR81, succinate via GPR91, and beta
      hydroxybutyrate via GPR109A. In addition, lactate activates hypoxia-inducible
      factor HIF1alpha and succinate promotes DNA methylation. GPR81 and GPR91 are
      tumor promoters, and increased production of lactate and succinate as their
      agonists drives tumorigenesis by enhancing signaling via these two receptors. In
      contrast, GPR109A is a tumor suppressor, and decreased synthesis of beta
      hydroxybutyrate as its agonist suppresses signaling via this receptor, thus
      attenuating the tumor-suppressing function of GPR109A. In parallel with the
      opposing changes in lactate/succinate and beta-hydroxybutyrate levels, tumor
      cells upregulate GPR81 and GPR91 but downregulate GPR109A. As such, these three
      metabolite receptors play a critical role in cancer and represent a new class of
      drug targets with selective antagonists of GPR81 and GPR91 for cancer treatment
      and agonists of GPR109A for cancer prevention.

PMID- 28512004
TI  - Contribution of high resolution peripheral quantitative CT to the management of
      bone and joint diseases.
AB  - Many imaging modalities have been described to diagnose and monitor osteoporosis
      (OP), osteoarthritis and inflammatory rheumatic diseases. Over the last ten
      years, High Resolution peripheral Quantitative Computerized Tomography (HR-pQCT)
      was shown to be a precise and non invasive technique to study bone and joint
      diseases in clinical research. It allows the study of both cortical and
      trabecular bone microarchitecture at the distal tibia and radius, and further
      applications have been developed such as the study of mechanical properties by
      the finite element analysis. Thus, in case-control and cross-sectional studies,
      microarchitecture parameters discriminated fractured individuals independently of
      areal BMD. Also, microstructure parameters can predict incident fracture in
      postmenopausal women. In metabolic diseases associated with bone fragility, HR
      pQCT may also be used to explore bone changes. In joint disease studies, HR-pQCT
      was a remarkable tool to assess bone erosion and joint space narrowing at the
      hand. This article gives an overview of this imaging technique.

PMID- 28512007
TI  - Antimalarial drug retinopathy: A typical " Bull's eyes " appearance of fundus.

PMID- 28512008
TI  - 3D printing and modelling of customized implants and surgical guides for non
      human primates.
AB  - BACKGROUND: Primate neurobiologists use chronically implanted devices such as
      pedestals for head stabilization and chambers to gain access to the brain and
      study its activity. Such implants are skull-mounted, and made from a hard,
      durable material, such as titanium. NEW METHOD: Here, we present a low-cost
      method of creating customized 3D-printed cranial implants that are tailored to
      the anatomy of individual animals. We performed pre-surgical computed tomography
      (CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models
      of the skull and brain. We then used 3D modelling software to design implantable
      head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides
      to aid us during surgery. Prototypes were made from plastic or resin, while
      implants were 3D-printed in titanium. The implants underwent post-processing and
      received a coating of osteocompatible material to promote bone integration.
      RESULTS: Their tailored fit greatly facilitated surgical implantation, and
      eliminated the gap between the implant and the bone. To date, our implants remain
      robust and well-integrated with the skull. COMPARISON WITH EXISTING METHOD(S):
      Commercial-off-the-shelf solutions typically come with a uniform, flat base,
      preventing them from sitting flush against the curved surface of the skull. This
      leaves gaps for fluid and tissue ingress, increasing the risk of microbial
      infection and tissue inflammation, as well as implant loss. CONCLUSIONS: The use
      of 3D printing technology enabled us to quickly and affordably create unique,
      complex designs, avoiding the constraints levied by traditional production
      methods, thereby boosting experimental success and improving the wellbeing of the
      animals.

PMID- 28512009
TI  - Combining D-cycloserine with appetitive extinction learning modulates amygdala
      activity during recall.
AB  - Appetitive Pavlovian conditioning plays a crucial role in the pathogenesis of
      drug addiction and conditioned reward cues can trigger craving and relapse even
      after long phases of abstinence. Promising preclinical work showed that the NMDA
      receptor partial agonist D-cycloserine (DCS) facilitates Pavlovian extinction
      learning of fear and drug cues. Furthermore, DCS-augmented exposure therapy seems
      to be beneficial in various anxiety disorders, while the supposed working
      mechanism of DCS during human appetitive or aversive extinction learning is still
      not confirmed. To test the hypothesis that DCS administration before extinction
      training improves extinction learning, healthy adults (n=32) underwent
      conditioning, extinction, and extinction recall on three successive days in a
      randomized, double-blind, placebo-controlled fMRI design. Monetary wins and
      losses served as unconditioned stimuli during conditioning to probe appetitive
      and aversive learning. An oral dose of 50mg of DCS or placebo was administered 1h
      before extinction training and DCS effects during extinction recall were
      evaluated on a behavioral and neuronal level. We found attenuated amygdala
      activation in the DCS compared to the placebo group during recall of the
      extinguished appetitive cue, along with evidence for enhanced functional amygdala
      vmPFC coupling in the DCS group. While the absence of additional physiological
      measures of conditioned responses during recall in this study prevent the
      evaluation of a behavioral DCS effect, our neuronal findings are in accordance
      with recent theories linking successful extinction recall in humans to modulatory
      top-down influences from the vmPFC that inhibit amygdala activation. Our results
      should encourage further translational studies concerning the usefulness of DCS
      to target maladaptive Pavlovian reward associations.

PMID- 28512010
TI  - Cerebellar learning modulates surface expression of a voltage-gated ion channel
      in cerebellar cortex.
AB  - Numerous experiments using ex vivo electrophysiology suggest that mammalian
      learning and memory involves regulation of voltage-gated ion channels in terms of
      changes in function. Yet, little is known about learning-related regulation of
      voltage-gated ion channels in terms of changes in expression. In two experiments,
      we examined changes in cell surface expression of the voltage-gated potassium
      channel alpha-subunit Kv1.2 in a discrete region of cerebellar cortex after
      eyeblink conditioning (EBC), a well-studied form of cerebellar-dependent
      learning. Kv1.2 in cerebellar cortex is expressed almost entirely in basket
      cells, primarily in the axon terminal pinceaux (PCX) region, and Purkinje cells,
      primarily in dendrites. Cell surface expression of Kv1.2 was measured using both
      multiphoton microscopy, which allowed measurement confined to the PCX region, and
      biotinylation/western blot, which measured total cell surface expression. In the
      first experiment, rats underwent three sessions of EBC, explicitly unpaired
      stimulus exposure, or context-only exposure and the results revealed a decrease
      in Kv1.2 cell surface expression in the unpaired group as measured with
      microscopy but no change as measured with western blot. In the second experiment,
      the same three training groups underwent only one half of a session of training,
      and the results revealed an increase in Kv1.2 cell surface expression in the
      unpaired group as measured with western blot but no change as measured with
      microscopy. In addition, rats in the EBC group that did not express conditioned
      responses (CRs) exhibited the same increase in Kv1.2 cell surface expression as
      the unpaired group. The overall pattern of results suggests that cell surface
      expression of Kv1.2 is changed with exposure to EBC stimuli in the absence, or
      prior to the emergence, of CRs.

PMID- 28512011
TI  - Modulation of alpha oscillations is required for the suppression of semantic
      interference.
AB  - Recent findings on alpha band oscillations suggest their important role in memory
      consolidation and suppression of external distractors such as environmental
      noise. However, less attention was given to the phenomenon of internal
      distracting information being solely inherent to the stimuli content. Human
      memory may be prone to internal distractions caused by semantic relatedness
      between the meaning of words (e.g., atom, neutron, nucleus, etc.) to be encoded,
      i.e., semantic interference. Our study investigates the brain oscillatory
      dynamics behind the semantic interference phenomenon, whose possible outcome is
      known as false memories. In this direction, Deese-Roediger-McDermott word lists
      were appropriated for a modified Sternberg paradigm in auditory modality.
      Participants received semantically related and unrelated word lists via
      headphones while EEG data were acquired. Semantic interference triggered the
      false memory rates to be higher than those of other types of memory errors.
      Analysis demonstrated that the upper part of alpha band (~10-12Hz) power
      decreases on parieto-occipital channels in the retention interval, prior to the
      probe item for semantically related condition. Our study elucidates the
      oscillatory mechanisms behind semantic interference by relying on alpha
      functional inhibition theory.

PMID- 28512012
TI  - Crustins are distinctive members of the WAP-containing protein superfamily: An
      improved classification approach.
AB  - Crustins are considered effector molecules of innate immunity in arthropods, and
      classification schemes have been proposed over the last 10 years. However,
      classification problems have emerged: for example, proteins that have been well
      identified as members of a particular category have also been classified as
      crustins. Therefore, the objective of this manuscript was to analyze and, based
      on solid arguments, improve the original proposed nomenclature to make crustins a
      distinctive group of antibacterial proteins. The presence of WAP or 4DSC domain
      has been considered a distinctive feature of crustins; however, several
      antibacterial proteins containing WAP domains have been detected in diverse
      taxonomic groups (including mammals). Here, we present evidence supporting the
      idea that the Cys-rich region and the 4DSC domain can be considered a signature
      of crustins and, together with some distance arrangements occurring within this
      12-Cys region, yield enough information for the classification of these proteins.
      Herein, the core characteristics to be considered for classification purposes are
      the length of the Gly-rich region and the repetitive tetrapeptides occurring
      within this region; these characteristics are then hierarchically followed by the
      F and A distances located within the 4DSC domain. Finally, the proposed system
      considers the crustin signature as the common structure in all members, which is
      a differentiator from other proteins containing WAP domains, separating crustins
      as a well-distinguished member of the superfamily of WAP-domain containing
      proteins.

PMID- 28512013
TI  - Evaluation of the N-latex serum free light chain assay on the Siemens BNII
      analyzer and agreement with The Binding Site FreeLite assay on the SPAPlus.
AB  - OBJECTIVES: To evaluate the Siemens N-latex kappa free light chain (kappaFLC) and
      lambda FLC (lambdaFLC) assays on the BNII nephelometer and assess agreement with
      The Binding Site Freelite FLC assays on the SPAPlus. DESIGN AND METHODS: Over 180
      patient serum samples from routine analysis of kappaFLC and lambdaFLC measured by
      the Freelite assay were collected for the study and measured with the N-latex
      kappaFLC and lambdaFLC assays to assess precision, linearity, method comparison
      and dilutional effects. RESULTS: Complex precision showed coefficients of
      variation of 4.8-7.2% for the kappaFLC assay and 3.6-6.0% for the lambdaFLC
      assay. Linearity assessment showed both assays were linear (kappaFLC, y=1.00x
      0.09 and lambdaFLC, y=1.050x-1.252). Qualitative method comparison showed 87.9%
      (116/132) agreement and Cohen's kappa of 80.4% between the kappaFLC assays and
      72.6% (98/135) agreement and Cohen's kappa of 55.4% for the lambdaFLC assays.
      Quantitative method comparison for kappaFLC<150mg/L was y=0.92x+2.21, R=0.661 and
      for lambdaFLC<150mg/L was y=7.90x-137.96, R=0.526. Dilutional effects including
      antigen excess and non-linearity were also examined. CONCLUSIONS: The N-latex
      assay showed good precision and linearity with reasonable agreement to the
      Freelite assay. However, the assays should not be used interchangeably to monitor
      patients.

PMID- 28512014
TI  - Expressional divergence of insect GOX genes: From specialist to generalist
      glucose oxidase.
AB  - Insect herbivores often secrete glucose oxidase (GOX) onto plants to counteract
      plant defenses and potential pathogens. Whether generalist herbivores always have
      significantly higher GOX activities than their specialist counterparts at any
      comparable stage or conditions and how this is realized remain unknown. To
      address these two general questions, we subjected larvae of a pair of sister
      species differed mainly in host range, the generalist Helicoverpa armigera and
      its specialist counterpart Helicoverpa assulta, to the same sets of stage,
      protein to digestible carbohydrate (P:C) ratio, allelochemical or host plant
      treatments for simultaneous analyses of GOX transcripts and activities in their
      labial glands. GOX activity and transcripts are upregulated concurrently with
      food ingestion and body growth, downregulated with stopping ingestion and
      wandering for pupation in both species. The three tested host plants upregulated
      GOX transcripts, and to a lesser extent, GOX activity in both species. There were
      significant differences in both GOX transcripts and activity elicited by
      allelochemicals, but only in GOX transcripts by P:C ratios in both species. GOX
      activities were higher in H. armigera than H. assulta in all the comparable
      treatments, but GOX transcripts were significantly higher either in generalists
      or in specialists, depending on the developmental stages, host plants, P:C ratio
      and allelochemicals they encounter. These data indicate that the greater GOX
      activity in generalist herbivores is not achieved by greater transcription rate,
      but by greater transcript stability, greater translation rate, better enzyme
      stability and/or their combination.

PMID- 28512015
TI  - The association between miR-34 dysregulation and distant metastases formation in
      lung adenocarcinoma.
AB  - Lung cancer has the highest mortality rate amongst human cancers and the majority
      of deaths can be attributed to metastatic spread. The miR-34 family includes
      three tumor suppressive miRs: miR-34a, miR-34b and miR-34c. miR-34 downregulation
      is a frequent observation in human malignancies and is often attributed to
      hypermethylation of the miR-34a and miR-34b/c promoters. Here, the potential
      association between aberrant miR-34 expression and promoter methylation and
      distant metastases formation in lung adenocarcinoma (LAC) is investigated. The
      expression levels of miR-34a, miR-34b and miR-34c, as well as the methylation
      status of the miR-34a and miR-34b/c promoters were determined in a LAC patient
      cohort comprising 26 non-metastasizing and 26 metastasizing primary LACs, as well
      as 24 paired distant metastases and 25 tumor-adjacent normal lung samples using
      RT-qPCR and Methylation-Sensitive High Resolution Melting (MS-HRM) analysis. No
      difference in expression was observed for miR-34a when comparing metastasizing
      and non-metastasizing LACs (p=0.793). For both miR-34b and miR-34c, a
      significantly lower expression level was determined in metastasizing LACs
      compared to non-metastasizing LACs (p=0.0005 and p=0.002) with similarly
      decreased expression levels observed in the paired distant metastases.
      Hypermethylation was detected in 35/51 LACs compared to 0/25 tumor-adjacent
      normal lungs for the miR-34a promoter (p<0.0001). Similarly, 18/51 LACs compared
      to 1/25 tumor-adjacent normal lungs showed hypermethylation of the miR-34b/c
      promoter (p=0.003). No difference in methylation was observed between
      metastasizing and non-metastasizing LACs for neither the miR-34a (p=0.832) nor
      the miR-34b/c (p=0.900) promoter. In conclusion, miR-34a and miR-34b/c promoter
      hypermethylation is a frequent event in LAC occurring in 68.7% and 35.3% of
      tested cases (n=51), respectively. Low miR-34b and miR-34c expression was
      associated with distant metastases formation in LAC. These changes can be
      targeted as novel biomarkers in LAC.

PMID- 28512016
TI  - Mechanism of action of AMP-jsa9, a LI-F-type antimicrobial peptide produced by
      Paenibacillus polymyxa JSa-9, against Fusarium moniliforme.
AB  - LI-F type peptides (AMP-jsa9) are a group of cyclic lipodepsipeptides that
      exhibit broad antimicrobial spectrum against Gram-positive bacteria and
      filamentous fungi. We sought to assess the toxicity of AMP-jsa9 and the mechanism
      of AMP-jsa9 action against Fusarium moniliforme. AMP-jsa9 exhibited weak
      hemolytic activity and weak cytotoxicity at antimicrobial concentrations
      (32MUg/ml). Confocal laser microscopy, SEM, and TEM indicated that AMP-jsa9
      primarily targets the cell wall, plasma membrane, and cytoskeleton, increases
      membranepermeability, and enhances cytoplasm leakage (e.g., K+, protein).
      Quantitative proteomic analysis using isobaric tags for relative and absolute
      quantitation (iTRAQ) detected a total of 162 differentially expressed proteins
      (59 up-regulated and 103 down-regulated) following treatment of F. moniliforme
      with AMP-jsa9. AMP-jsa9 treatment also led to reductions in chitin, ergosterol,
      NADH, NADPH, and ATP levels. Moreover, fumonisin B1 expression and biosynthesis
      was suppressed in AMP-jsa9-treated F. moniliforme. Our results provide a
      theoretical basis for the application of AMP-jsa9 as a natural and effective
      antifungal agent in the agricultural, food, and animal feed industries.

PMID- 28512017
TI  - A case of autoimmune severe acquired von Willebrand syndrome (type 3-like).
AB  - Von Willebrand disease (VWD) is the most common congenital bleeding disorder and
      is due to quantitative or qualitative defects of von Willebrand factor (VWF).
      Acquired defects of VWF, termed acquired von Willebrand syndrome (AVWS), are due
      to a host of different mechanisms. Autoantibody-mediated AVWS may be associated
      with lymphoproliferative or immunological disorders, such as systemic lupus
      erythematosus (SLE). A large majority of AVWS cases are type 1 or type 2A-like
      and patients tend to have a mild to moderate bleeding tendency. We report a case
      of severe autoimmune AVWS in a woman with SLE who presented with clinical and
      laboratory features of type 3 VWD (undetectable VWF antigen, ristocetin cofactor
      activity, and VWF multimers). A mixing study demonstrated an inhibitor to VWF
      (6BU/mL). Her bleeds were managed with antifibrinolytics, recombinant activated
      factor VII, and activated prothrombin complex concentrate. She was initially
      treated with steroids and intravenous immunoglobulin therapy. However, her
      bleeding symptoms continued until she was treated with rituximab, and her VWF
      parameters normalized. She relapsed two years later due to non-compliance with
      her immunosuppressive medications and expired another two years later secondary
      to complications of sepsis and uremic pericarditis. This case emphasizes the
      importance of aggressive initial therapy of SLE to reduce secondary
      complications, frequent patient monitoring, and continued treatment of the
      underlying autoimmune disorder in patients with AVWS.

PMID- 28512018
TI  - Nanoencapsulation of a glucocorticoid improves barrier function and anti
      inflammatory effect on monolayers of pulmonary epithelial cell lines.
AB  - The anti-inflammatory effect of polymeric deflazacort nanocapsules (NC-DFZ) was
      investigated, and possible improvement of epithelial barrier function using
      filter grown monolayers of Calu-3 cells was assessed. NC prepared from
      poly(epsilon-caprolactone) (PCL) had a mean size around 200nm, slightly negative
      zeta potential (~-8mV), and low polydispersity index (<0.10). Encapsulation of
      DFZ had an efficiency of 85%. No cytotoxic effects were observed at particle
      concentration of 9.85*1011NC/ml, which was therefore chosen to evaluate the
      effect of NC-DFZ at 1% (w/v) of PCL and 0.5% (w/v) of DFZ on the epithelial
      barrier function of Calu-3 monolayers. Nanoencapsulated drug at 0.5% (w/v)
      increased transepithelial electrical resistance and decreased permeability of the
      paracellular marker sodium fluorescein, while non-encapsulated DFZ failed to
      improve these parameters. Moreover, NC-DFZ reduced the lipopolysaccharide (LPS)
      mediated secretion of the inflammatory marker IL-8. In vitro dissolution testing
      revealed controlled release of DFZ from nanocapsules, which may explain the
      improved effect of DFZ on the cells. These data suggest that nanoencapsulation of
      pulmonary delivered corticosteroids could be advantageous for the treatment of
      inflammatory conditions, such as asthma and chronic obstructive pulmonary
      diseases.

PMID- 28512019
TI  - Novel inulin-based mucoadhesive micelles loaded with corticosteroids as potential
      transcorneal permeation enhancers.
AB  - In this work a new copolymer of inulin (INU) derivatized with ethylendiamine
      (EDA) and retinoic acid (RA), named INU-EDA-RA, was synthetized, characterized
      and employed to produce micelles as carriers for topical administration of
      corticosteroids for the potential treatment of diseases of posterior eye segment.
      Spectroscopic analysis confirmed a molar derivatization degree of 11.30 and 4.30%
      in EDA and RA, respectively. INU-EDA-RA micelles are capable of strong
      mucoadhesive interactions which result time-independent and stable over time but
      concentration depending. Moreover micelles are able to encapsulate efficiently
      from 3 to 13% (w/w) of lipophilic drugs, as dexamethasone, triamcinolone and
      triamcinolone acetonide. Drug loaded micelles are stable for three months when
      stored as freeze-dried powders and able to release high amount of drug when
      compared to drug dissolution profiles from suspensions. Moreover, drug loaded
      micelles are compatible with different ocular cell lines that are also able to
      internalize fluorescent micelles. Finally, drug loaded micelles enhance drug
      fluxes and permeability coefficients across corneal epithelial cells, thus
      reducing drug loss due to retention inside the cells.

PMID- 28512020
TI  - Molecular epidemiology of porcine reproductive and respiratory syndrome virus in
      Central China since 2014: The prevalence of NADC30-like PRRSVs.
AB  - Porcine reproductive and respiratory syndrome (PRRS), characterized by
      respiratory disorders in piglets and reproductive failure in sows, is still the
      great threat of swine industry. Recently, Emergence of the novel NADC30-like PRRS
      viruses (PRRSVs) has caused widespread outbreaks of PRRS. To investigate the
      epidemic characteristics of PRRSVs in Central China since 2014, 6372 clinical
      serum samples were tested by ELISA, 250 tissue samples were tested by RT-PCR, and
      among these, 30 ORF5 and 17 Nsp2 genes sequences were analyzed. Phylogenetic tree
      based on ORF5 revealed that, 17 isolates were clustered into subgroup 1,
      represented by the NADC30. And for the Nsp2, The strains which had a
      discontinuous 131-amino-acid deletion in Nsp2, called NADC30-like strains, were
      clustered into subgroup 2. Our data suggested that the NADC30-like PRRSV strains
      spread quickly and are now circulating and prevalent in Central China as well as
      the classical HP-PRRSV strains. In addition, amino acid variation analysis of GP5
      revealed that the amino acid sequences of NADC30-like PRRSV strains underwent
      rapid evolution and contained extensive amino acid substitutions in important
      motifs, such as potential neutralization epitope and the N-glycosylation sites.
      In summary, our data would provide a large amount of detailed information on
      molecular variation and genetic diversity of PRRSV in central China.

PMID- 28512021
TI  - Statin Use After Diagnosis of Colon Cancer and Patient Survival.
AB  - BACKGROUND & AIMS: Statin use has been associated with a reduced incidence of
      colorectal cancer and might also affect survival of patients diagnosed with colon
      cancer. Statins are believed to inhibit Ras signaling and may also activate the
      bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells. We
      investigated the effects of statins on overall survival of patients with a
      diagnosis of colon cancer, and whether their effects were associated with changes
      in KRAS or the BMP signaling pathways. METHODS: Data were derived from the PHARMO
      database network (Netherlands) and linked to patients diagnosed with colon cancer
      from 2002 through 2007, listed in the Eindhoven Cancer Registry. We obtained
      information on causes of death from statistics Netherlands. We constructed a
      tissue microarray of 999 colon cancer specimens from patients who underwent
      surgical resection from 2002 through 2008. Survival was analyzed with statin user
      status after diagnosis as a time-dependent covariate. Multivariable Poisson
      regression survival models and Cox analyses were used to study the effect of
      statins on survival. Tumor tissues were analyzed by immunohistochemistry for
      levels of SMAD4, BMPR1A, BMPR1B, and BMPR2 proteins. Tumor tissues were
      considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A,
      BMPR1B, or BMPR2. DNA was isolated from tumor tissues and analyzed by
      quantitative polymerase chain reaction to detect mutations in KRAS. The primary
      outcome measures were overall mortality and cancer-specific mortality. RESULTS:
      In this cohort, 21.0% of the patients (210/999) were defined as statin users
      after diagnosis of colon cancer. Statin use after diagnosis was significantly
      associated with reduced risk of death from any cause (adjusted relative risk
      [RR], 0.67; 95% confidence interval [CI], 0.51-0.87; P = .003) and death from
      cancer (adjusted RR, 0.66; 95% CI, 0.49-0.89; P = .007). Statin use after
      diagnosis was associated with reduced risk of death from any cause or from cancer
      for patients whose tumors had intact BMP signaling (adjusted RR, 0.39; 95% CI,
      0.22-0.68; P = .001), but not for patients whose tumors did not have BMP
      signaling (adjusted RR, 0.81; 95% CI, 0.55-1.21; P = .106; P < .0001 for the
      interaction). Statin use after diagnosis was not associated with reduced risk of
      death from any cause or from cancer for patients whose tumors did not contain
      KRAS mutations (adjusted RR, 0.81; 95% CI, 0.56-1.18; P = .273) or whose tumors
      did have KRAS mutations (adjusted RR, 0.59; 95% CI 0.35-1.03; P = .062; P = .90
      for the interaction). CONCLUSIONS: In an analysis of 999 patients with a
      diagnosis of colon cancer, we associated statin with reduced risk of death from
      any cause or from cancer. The benefit of statin use is greater for patients whose
      tumors have intact BMP signaling, independent of KRAS mutation status. Randomized
      controlled trials are required to confirm these results.

PMID- 28512022
TI  - Synthesis, antimycobacterial activity and docking study of 2-aroyl
      [1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives and related hydrazide
      hydrazones.
AB  - A new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol
      4(1H)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues
      4a-e was presented. The antimycobacterial activity against reference strain
      Mycobacterium tuberculosis H37Rv and cytotoxicity against the human embryonic
      kidney cell line HEK-293 were tested in vitro. All compounds demonstrated
      significant minimum inhibitory concentrations (MIC) ranging 0.28-1.69MUM, which
      were comparable to those of isoniazid. The cytotoxicity (IC50>200uM) to the
      "normal cell" model HEK-293T exhibited by 2-aroyl-[1]benzopyrano[4,3-c]pyrazol
      4(1H)-one derivatives 5b-e, was noticeably milder compared to that of their
      hydrazone analogues 4a-e (IC50 33-403uM). Molecular docking studies on compounds
      4a-e and 5b-g were also carried out to investigate their binding to the 2-trans
      enoyl-ACP reductase (InhA) enzyme involved in M. tuberculosis cell wall
      biogenesis. The binding model suggested one or more hydrogen bonding and/or arene
      H or arene-arene interactions between hydrazones or pyrazole-fused coumarin
      derivatives and InhA enzyme for all synthesized compounds.

PMID- 28512023
TI  - Synthesis and biological evaluation of novel 5-aryl-4-(5-nitrofuran-2-yl)
      pyrimidines as potential anti-bacterial agents.
AB  - A facile two-step synthetic approach to fluorinated and non-fluorinated 5-aryl-4
      (5-nitrofuran-2-yl)-pyrimidines from readily available 5-bromo-4-(furan-2
      yl)pyrimidine has been developed. All synthesized compounds were screened in
      vitro for their antibacterial activities against twelve various bacterial
      strains. It is demonstrated that some of these compounds exhibited significant
      antibacterial activities against strains Neisseria gonorrhoeae and Staphylococcus
      aureus, comparable and even higher with that commercial drug Spectinomycin.

PMID- 28512025
TI  - Synthesis of methanesulphonamido-benzimidazole derivatives as gastro-sparing
      antiinflammatory agents with antioxidant effect.
AB  - A series of 5-methanesulphonamido benzimidazole derivatives were designed by
      combining the structural features of clinically useful anti-inflammatory drugs
      (nimesulide and rofecoxib) and antiulcer drugs (lansoprazole, omeprazole, etc.)
      based on physicochemical and 3D similarity studies. The compounds were evaluated
      for their anti-inflammatory activity in carrageenan induced rat paw edema model
      taking rofecoxib and indomethacin as standard drugs. In vitro antioxidant
      activity of the compounds was assessed by potassium ferricyanide reducing power
      (PFRAP) assay. The compounds 9, 10 and 11 showed anti-inflammatory activity
      comparable to the standard group and were also non-ulcerogenic at the test doses.
      Compounds 6-11 exhibited good antioxidant effect in the concentration range (1.0
      50.0umol/ml. Preliminary theoretical ADME profiling of the compounds based on
      computation of selected physicochemical properties showed an excellent compliance
      with Lipinski's rule.

PMID- 28512024
TI  - Repurposing of Proton Pump Inhibitors as first identified small molecule
      inhibitors of endo-beta-N-acetylglucosaminidase (ENGase) for the treatment of
      NGLY1 deficiency, a rare genetic disease.
AB  - N-Glycanase deficiency, or NGLY1 deficiency, is an extremely rare human genetic
      disease. N-Glycanase, encoded by the gene NGLY1, is an important enzyme involved
      in protein deglycosylation of misfolded proteins. Deglycosylation of misfolded
      proteins precedes the endoplasmic reticulum (ER)-associated degradation (ERAD)
      process. NGLY1 patients produce little or no N-glycanase (Ngly1), and the
      symptoms include global developmental delay, frequent seizures, complex
      hyperkinetic movement disorder, difficulty in swallowing/aspiration, liver
      dysfunction, and a lack of tears. Unfortunately, there has not been any
      therapeutic option available for this rare disease so far. Recently, a proposed
      molecular mechanism for NGLY1 deficiency suggested that endo-beta-N
      acetylglucosaminidase (ENGase) inhibitors may be promising therapeutics for NGLY1
      patients. Herein, we performed structure-based virtual screening utilizing FDA
      approved drug database on this ENGase target to enable repurposing of existing
      drugs. Several Proton Pump Inhibitors (PPIs), a series of substituted 1H-benzo
      [d] imidazole, and 1H-imidazo [4,5-b] pyridines, among other scaffolds, have been
      identified as potent ENGase inhibitors. An electrophoretic mobility shift assay
      was employed to assess the inhibition of ENGase activity by these PPIs. Our
      efforts led to the discovery of Rabeprazole Sodium as the most promising hit with
      an IC50 of 4.47+/-0.44MUM. This is the first report that describes the discovery
      of small molecule ENGase inhibitors, which can potentially be used for the
      treatment of human NGLY1 deficiency.

PMID- 28512026
TI  - One-pot synthesis and biological evaluation of N-(aminosulfonyl)-4
      podophyllotoxin carbamates as potential anticancer agents.
AB  - A series of N-(aminosulfonyl)-4-podophyllotoxin carbamates were synthesized via
      the Burgess-type intermediate, and their antiproliferative activities were
      evaluated. Most of them possessed more potent cytotoxic effects against four
      human tumor cell lines (HeLa, A-549, HCT-8 and HepG2) and less toxic to normal
      human fetal lung fibroblast WI-38 cells than etoposide. In particular, N
      (morpholinosulfonyl)-4-podophyllotoxin carbamate (9) exhibited the most potent
      activity towards these four tumor cells with IC50 values in the range of 0.5
      16.5MUM. Furthermore, immunofluorescence analysis revealed that 9 induced cell
      apoptosis by up-regulating the expression of p53 and ROS. Meanwhile, 9
      effectively inhibited tubulin polymerization and microtubule assembly at cellular
      levels in HeLa cells. In addition, 9 could induce cell cycle arrest in the G2/M
      phase in HeLa cells by up-regulating levels of cyclinB1 and cdc2 and decreasing
      the expression of p-cdc2. These results indicated that 9 had potential for
      further development as anticancer agents.

PMID- 28512027
TI  - Insights into the myosin II inhibitory potency of A-ring-modified (S)
      blebbistatin analogs.
AB  - Myosin II is an interesting target for therapeutic intervention, as it is
      involved in a large number of motility-based diseases. (S)-Blebbistatin is a
      known micromolar inhibitor of this protein. A new series of (S)-blebbistatin
      derivatives with a modified A-ring was synthesized and the myosin II inhibitory
      properties were evaluated in vitro. In this way, we gained insight into the
      influence of structural modifications in this part of the scaffold on myosin II
      inhibitory potency. Our results indicate there are few possibilities for potency
      enhancement via ring A modification of the blebbistatin scaffold.

PMID- 28512028
TI  - Evaluation of synthesized coumarin derivatives on aromatase inhibitory activity.
AB  - In women across the world, the most common type of cancer is breast cancer. Among
      medical treatments, endocrine therapy based on aromatase inhibitors (AI) is
      expected to be effective against not only post-menopausal but also pre-menopausal
      breast cancer. In this study, we examined the structure-activity relationship
      between the aromatase inhibitory effects of 7-diethylaminocoumarin derivatives
      with a substituent at position 3 and coumarin derivatives with a substituent at
      position 7. Consequently, we found that 7-(pyridin-3-yl)coumarin (IC50 values
      30.3nM) and 7,7'-diethylamino-3,3'-biscoumarin (28.7nM) are the most potent
      inhibitors of aromatase. These inhibitors were found to be comparable to the
      existing CYP19 inhibitor exemestane (42.5nM).

PMID- 28512029
TI  - Calixarene-mediated liquid membrane transport of choline conjugates 3: The effect
      of handle variation on neurotransmitter transport.
AB  - Upper rim phosphonic acid functionalized calix[4]arene affects selective
      transport of multiple molecular payloads through a liquid membrane. The secret is
      in the attachment of a receptor-complementary handle to the payload. We find that
      the trimethylammonium ethylene group present in choline is one of several general
      handles for the transport of drug and drug-like species. Herein we compare the
      effect of handle variation against the transport of serotonin and dopamine. We
      find that several ionizable amine termini handles are sufficient for transport
      and identify two ideal candidates. Their performance is significantly enhanced in
      HEPES buffered solutions. This inquiry completes a series of 3 studies aimed at
      optimization of this strategy. In completion a new approach towards synthetic
      receptor mediated selective small molecule transport has emerged; future work in
      vesicular and cellular systems will follow.

PMID- 28512030
TI  - Discovery of potent and orally active 1,4-disubstituted indazoles as novel
      allosteric glucokinase activators.
AB  - Guided by co-crystal structural information obtained from a different series we
      were exploring, a scaffold morphing and SBDD approach led to the discovery of the
      1,4-disubstituted indazole series as a novel class of GKAs that potently activate
      GK in enzyme and cell assays. anti-diabetic OGTT efficacy was demonstrated with
      29 in a rodent models of type 2 diabetes.

PMID- 28512031
TI  - From a novel HTS hit to potent, selective, and orally bioavailable KDM5
      inhibitors.
AB  - A high-throughput screening (HTS) of the Genentech/Roche library identified a
      novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding
      mode, initial attempts to improve inhibitor potency failed to improve potency,
      and synthesis of analogs was further hampered by the presence of a C-C bond
      between the pyrrolidine and pyridine. Replacing this with a C-N bond
      significantly simplified synthesis, yielding pyrazole analog 35, of which we
      obtained a co-crystal structure with KDM5A. Using structure-based design
      approach, we identified 50 with improved biochemical, cell potency and reduced MW
      and lower lipophilicity (LogD) compared with the original hit. Furthermore, 50
      showed lower clearance than 9 in mice. In combination with its remarkably low
      plasma protein binding (PPB) in mice (40%), oral dosing of 50 at 5mg/kg resulted
      in unbound Cmax ~2-fold of its cell potency (PC9 H3K4Me3 0.96MUM), meeting our
      criteria for an in vivo tool compound from a new scaffold.

PMID- 28512032
TI  - Cytotoxic triterpene diglycosides from the sea cucumber Stichopus horrens.
AB  - Using various chromatographic separation techniques, eight triterpene
      diglycosides (1-8), including four new compounds namely stichorrenosides A-D (1
      4), were isolated from a methanol extract of the Vietnamese sea cucumber S.
      horrens. Their structures were elucidated based on spectroscopic analyses,
      including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against
      five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid
      carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2
      (melanoma), was evaluated using SRB methods. Stichorrenoside D (4), stichoposide
      A (5), and 3beta-O-[beta-d-xylopyranosyl-(1->2)-beta-d-xylopyranosyl]-23S
      acetoxyholost-7-ene (7) showed strong cytotoxicity on all five tested cancer cell
      lines, whereas significant effect was observed for stichorrenoside C (3) and
      stichoposide B (6).

PMID- 28512033
TI  - Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine
      and behavioral alterations in mice.
AB  - Emerging evidence suggests that there is a window of opportunity within the early
      developmental period, when microbiota-based interventions could play a major role
      in modulating the gut-brain axis and, thereby, in preventing mood disorders. This
      study aims at evaluating the effects and mode of action of Bifidobacterium
      pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by
      maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four
      groups, which were subjected or not to MS and supplemented with placebo or B.
      pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until
      P41. Behavioral tests were performed and neuroendocrine parameters were analyzed
      including corticosterone, cytokine/chemokine concentrations and
      neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene
      sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects
      of the excessive MS-induced stress response of the hypothalamic-pituitary-adrenal
      (HPA) axis, particularly corticosterone production at baseline and in response to
      subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down
      regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN
      gamma]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA]
      and adrenaline [A] concentrations) at P21. These effects have a long-term impact
      on the central nervous system (CNS) of adult mice since MS mice fed B.
      pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice,
      as well as normal neurotransmitter levels in the hypothalamus. The anti
      inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an
      improvement in glucocorticoid sensitivity in mesenteric lymph node
      immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT
      7765 to MS animals also reversed intestinal dysbiosis affecting the proportions
      of ten Operational Taxonomic Units (OTUs) at P21, which could partly explain the
      restoration of immune, neuroendocrine and behavioral alterations caused by stress
      in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765
      is able to beneficially modulate the consequences of chronic stress on the HPA
      response produced by MS during infancy with long-lasting effects in adulthood,
      via modulation of the intestinal neurotransmitter and cytokine network with short
      and long-term consequences in brain biochemistry and behavior.

PMID- 28512034
TI  - Diagnostic yield of capsule endoscopy versus magnetic resonance enterography and
      small bowel contrast ultrasound in the evaluation of small bowel Crohn's disease:
      Systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Capsule endoscopy (CE), magnetic resonance enterography
      (MRE) and small bowel (SB) intestinal contrast ultrasound (SICUS) are the
      modalities of choice for SB evaluation. This study aimed to compare the
      diagnostic yield (DY) of CE to MRE and SICUS in detection and monitoring of SB CD
      through meta-analysis of the available literature. METHODS: We performed a
      systematic literature search for trials comparing the accuracy of CE, MRE and
      SICUS for detection of active SB inflammation in patients with suspected and/or
      established CD. Only prospective studies comparing CE with another additional
      diagnostic modality were included in the final analysis. Pooled odds ratios (ORs)
      for the DY of the three modalities were calculated. RESULTS: A total of 112
      studies were retrieved; following selection, 13 studies were eligible for
      analysis. The DY of CE for detection of active SB CD was similar to that of MRE
      (10 studies, 400 patients, OR 1.17; 95% CI 0.83-1.67) and SICUS (5 studies, 142
      patients, OR 0.88; 95% CI 0.51-1.53). The outcomes were similar for the subgroups
      of suspected versus established CD and adult versus pediatric patients. CE was
      superior to MRE for proximal SB CD (7 studies, 251 patients, OR 2.79; 95% CI 1.2
      6.48); the difference vs SICUS was not significant. CONCLUSION: CE, MRE and SICUS
      have similar DY for detection of SB CD in both suspected and established CD. CE
      is superior to MRE for detection of proximal SB disease, however the risk of
      capsule retention should be considered.

PMID- 28512035
TI  - The predatory behavior of the Neotropical social wasp Polybia rejecta.
AB  - We experimentally studied the predatory behavior of Polybia rejecta (Vespidae,
      Polistinae, Epiponini) towards 2-88 mm-long insects attracted to a UV light trap.
      Foragers, which began to hunt at 6:30, selected 4-14 mm-long prey insects. Prey
      detection by sight by hovering wasps was confirmed using decoys. After the wasps
      landed and walked along a sinuous path, prey were detected by contact or from a
      distance (1-3cm). This was followed by seizure, stinging (contrarily to most
      other known cases), prey manipulation and retrieval. Prey that flew off might be
      caught in flight. The prey load, representing 30.7% of a forager's weight, was
      optimized by capturing up to six small prey or two medium-sized prey successively
      (both of which might be consumed in situ). The foragers cut off the wings of
      larger prey or cut them into two pieces and returned to gather the second piece.
      The handling time increased exponentially with the weight of the prey. Partial
      loading (i.e., retrieving a load much inferior to the maximum possible) was
      likely related to social facilitation, a form of nest-based recruitment that was
      demonstrated through the experimental elimination of local enhancement by
      removing foragers (both mechanisms favor the exploitation of favorable patches).

PMID- 28512036
TI  - Vocal responses of austral forest frogs to amplitude and degradation patterns of
      advertisement calls.
AB  - Degradation phenomena affecting animal acoustic signals may provide cues to
      assess the distance of emitters. Recognition of degraded signals has been
      extensively demonstrated in birds, and recently studies have also reported
      detection of degraded patterns in anurans that call at or above ground level. In
      the current study we explore the vocal responses of the syntopic burrowing male
      frogs Eupsophus emiliopugini and E. calcaratus from the South American temperate
      forest to synthetic conspecific calls differing in amplitude and emulating
      degraded and non-degraded signal patterns. The results show a strong dependence
      of vocal responses on signal amplitude, and a general lack of differential
      responses to signals with different pulse amplitude modulation depths in E.
      emiliopugini and no effect of relative amplitude of harmonics in E. calcaratus.
      Such limited discrimination of signal degradation patterns from non-degraded
      signals is likely related to the burrowing habits of these species. Shelters
      amplify outgoing and incoming conspecific vocalizations, but do not counteract
      signal degradation to an extent comparable to calling strategies used by other
      frogs. The limited detection abilities and resultant response permissiveness to
      degraded calls in these syntopic burrowing species would be advantageous for
      animals communicating in circumstances in which signal alteration prevails.

PMID- 28512037
TI  - Understanding behavior under nonverbal transitive-inference procedures: Stimulus
      control-topography analyses.
AB  - Following training with verbal stimulus relations involving A is greater than B
      and B is greater than C, verbally-competent individuals reliably select A>C when
      asked "which is greater, A or C?" (i.e., verbal transitive inference). This
      result is easy to interpret. Nonhuman animals and humans with and without
      intellectual disabilities have been exposed to nonverbal transitive-inference
      procedures involving trained arbitrary stimulus relations. Following the training
      of A+B-, B+C-, C+D-, and D+E-, B reliably is selected over D (i.e., nonverbal
      transitive inference). Such findings are more challenging to interpret. The
      present research explored accounts of nonverbal transitive inference based in
      transitive inference per se, reinforcement, such as value-transfer theory, and
      operant stimulus control. In Experiment 1, college students selected B>G
      following the training of A+B-, B+C-, C+D-///E+F-, F+G-, and G+H-
      (where///signifies the omission of D+E-). In Experiment 2, college students
      selected B>G following the training of A+B-, B+C-, C+D-///E+F-, F+G-, and G+X-
      (where X refers to 10 stimuli that alternated across trials). In Experiment 3,
      college students selected G>B following the training of Y+B-, B+C-, C+D-///E+F-,
      F+G-, and G+X- (where Y and X refer to 10 stimuli, respectively, that alternated
      across trials). These findings are discussed in the context of operant stimulus
      control by offering an approach based in stimulus B typically acquiring only a
      select stimulus control topography.

PMID- 28512038
TI  - Involvement of the oxytocin system in the nucleus accumbens in the regulation of
      juvenile social novelty-seeking behavior.
AB  - Exploration of novel environments, stimuli, and conspecifics is highly adaptive
      during the juvenile period, as individuals transition from immaturity to
      adulthood. We recently showed that juvenile rats prefer to interact with a novel
      individual over a familiar cage mate. However, the neural mechanisms underlying
      this juvenile social novelty-seeking behavior remain largely unknown. One
      potential candidate is the oxytocin (OXT) system, given its involvement in
      various motivated social behaviors. Here, we show that administration of the
      specific oxytocin receptor antagonist desGly-NH2,d(CH2)5-[Tyr(Me)2,Thr4]OVT
      reduces social novelty seeking-behavior in juvenile male rats when injected into
      the nucleus accumbens (10ng/0.5MUl/side). The same drug dose was ineffective at
      altering social novelty-seeking behavior when administered into the lateral
      septum or basolateral amygdala. These results are the first to suggest the
      involvement of the OXT system in the nucleus accumbens in the regulation of
      juvenile social novelty-seeking behavior.

PMID- 28512039
TI  - Fluorescein-Guided Surgery for High-Grade Glioma Resection: An Intraoperative
      "Contrast-Enhancer".
AB  - BACKGROUND: Fluorescein sodium salt is widely used in medicine as fluorescein
      isothiocyanate and commonly named fluorescein (FL). This fluorophore has been
      used as a fluorescent tracer for many applications, especially in ophthalmic
      surgery. It was initially used in neuro-oncology in 1948 to control tumor
      resection margins. After a transient disuse, it has recently had a second spring
      with the development of dedicated filters for operating microscopes, although it
      is still under evaluation in clinical use. The aim of this study is to contribute
      to the investigation according to which FL-guided surgery for high-grade glioma
      (HGG) is related to better rates of gross total resection (GTR) and so to a
      better outcome. METHODS: We retrospectively analyzed 23 cases of patients with
      new diagnosis of HGG, operated on in our unit by intraoperative FL use with a
      filter system directly integrated into an operative microscope (group 1).
      Fluorescence was compared with histology by biopsies carried out both in the
      fluorescent areas and in the periphery of fluorescent areas. Group 1 was matched
      with a control group of 25 patients with HGG operated on in our unit during the
      last 2 years without FL guidance (group 2). RESULTS: No side effects occurred
      related to FL. Histology and intraoperative neuronavigation showed strong
      correspondence with fluorescent and nonfluorescent areas. GTR rate was
      significantly higher in group 1 (82.6%) than in group 2 (52%). CONCLUSIONS:
      Intraoperative fluorescein-guided surgery showed safety and feasibility. Our and
      other studies suggest an improvement of GTR rate in HGG than nonuse.

PMID- 28512040
TI  - Meningiomas Adjacent to Major Venous Sinuses-Clinical Outcome and Recurrence.
AB  - BACKGROUND: Surgical treatment of meningiomas next to venous sinuses is difficult
      because of their irregular growth patterns and infiltration into the venous
      sinuses, making gross total resection impossible in some patients. We evaluated
      the postoperative clinical and neurologic course of this tumor subgroup. METHODS:
      This study included 141 consecutive patients with meningioma located within 20 mm
      of a major venous sinus. Complete data sets were available for all patients. We
      reviewed patient charts and surgical reports for demographics, histology, and
      clinical and neurologic performance preoperatively and postoperatively and during
      follow-up. Radiographic images were screened for tumor extension, infiltration
      into the skull, sinus infiltration (Sindou grade), extent of resection (Simpson
      grade), and tumor recurrence. RESULTS: Immediate postoperative neurologic
      improvement was found in 53.7% (n = 36) of patients with preoperative neurologic
      deficits (n = 67). Follow-up was up to 13.5 years. Medical Research Council
      Neurological Performance Scale and Karnofsky performance scale postoperatively
      improved in 24.1% and 55.3% of patients, respectively. Local tumor recurrence was
      detected in 10.6% (n = 15) of patients. Higher World Health Organization grade (P
      = 0.03), tumor size (P = 0.001), and bone invasion (P = 0.002) were predictors of
      local tumor recurrence. The median MIB-1 labeling index in patients with tumor
      recurrence was twice as high as in patients without recurrence. CONCLUSIONS:
      Surgical removal of meningiomas adjacent to venous sinuses reduces neurologic
      impairment and enables local tumor control in most patients. Tumor size, bone
      infiltration, and higher World Health Organization grade are important predictors
      of tumor recurrence.

PMID- 28512041
TI  - Characteristics of Blood Pressure Profiles After Endovascular Coiling as
      Predictors of Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.
AB  - OBJECTIVE: Accurate identification of patients who will achieve a favorable
      outcome is almost impossible preoperatively or postoperatively in poor-grade
      (Hunt and Hess Grade IV and V) aneurysmal subarachnoid hemorrhage (SAH). Whether
      characteristics of blood pressure profiles during the first 24 hours after
      endovascular coiling could predict prognosis in poor grade patients was explored.
      METHODS: Data were obtained retrospectively on all patients undergoing
      endovascular treatment with poor-grade SAH from November 2011 to June 2016. Blood
      pressure during the initial 24 hours was measured at 2-hour intervals after coil
      embolization. Studied features of mean systolic blood pressure (MSBP) and
      systolic blood pressure variability (SBPV) as well as demographics, medical
      history, clinical characteristics, and neurologic outcomes were documented. SBPV
      was determined as standard deviation and successive variation of systolic blood
      pressure. Logistic regression analysis was used to identify predictors of
      favorable outcome assessed on modified Rankin Scale score of 0 to 2. RESULTS: The
      patients with favorable and unfavorable outcome were comparable with respect to
      systolic blood pressure on admission and MSBP after coiling. However, MSBP
      between 120 and 140 mm Hg was one of independent predictors of good outcomes at
      discharge (odds ratio 7.1; P = 0.002). SBPV-successive variation after
      embolization was associated with functional recovery (odds ratio 0.87; P = 0.011)
      in multivariate logistic analysis and mortality by Cox proportional hazard
      regression (hazard ratio, 1.10; P = 0.001) at 6-month follow-up. CONCLUSIONS:
      Characteristics of blood pressure profiles after coiling appeared to be simple
      and convenient indexes for the prognosis of patients with poor-grade SAH.

PMID- 28512042
TI  - The Corona Dentis: Description of an Anatomic Variant with Technical Implications
      for Anterior Odontoid Screw Placement.
AB  - BACKGROUND: Type 2 odontoid fractures are the most common cervical fractures
      among the elderly. Neurologic deficit is usually caused by myelopathy as a result
      of posterior dens migration. Direct anterior screw placement provides
      stabilization and can preserve C1-C2 movement. The presence of a bony excrescence
      on the anterior superior tip of the dens may lead to placement of a screw of
      incorrect length. METHODS: Twenty C2 dry specimens were examined for the presence
      of a corona dentis, which is a bony excrescence in the coronal plane near the
      apex of the dens. When identified, measurements of the corona dentis were
      performed using calipers and a ruler. In addition, anteroposterior (AP) and
      lateral fluoroscopy was performed on all specimens found to have a corona dentis.
      RESULTS: A corona dentis was found on 20% of our C2 specimens and had an average
      width of 9 mm and an average height of 4.5 mm. The average width of the dens did
      not vary as the normal tip of the dens transitioned into the coronae. In no
      specimen did the corona dentis seem to be composed of trabecular bone and it was
      seen as a superior projection of cortical bone on fluoroscopy. On fluoroscopy,
      the corona dentis could be identified on a true AP projection. In angulated AP
      views, fluoroscopic images overestimated the length of the corona dentis.
      CONCLUSIONS: We describe a new entity termed the corona dentis because of its
      crownlike feature. It is a superior cortical bone protrusion and should be noted
      as a variant of the dens during anterior odontoid screw placement. Its propensity
      to increase the height of the dens markedly can lead to higher rates of
      neurologic deficits during type 2 odontoid fractures if not appreciated. A true
      AP view is critical for correct screw size placement.

PMID- 28512043
TI  - Endoscopic Assisted Supraorbital Keyhole Approach or Endoscopic Endonasal
      Approach in Cases of Tuberculum Sellae Meningioma: Which Surgical Route Should Be
      Favored?
AB  - OBJECTIVE: Keyhole approaches are under investigation for skull base tumor
      surgery. They are expected to have a low complication rate with the same
      successful resection rate compared with endoscopic endonasal procedures. In this
      study, we compare our current series of tuberculum sellae meningiomas resected
      via an endoscopic endonasal or microsurgical supraorbital keyhole approach.
      METHODS: Between 2011 and 2016, 16 patients were treated using the supraorbital
      keyhole procedure and 6 patients received an endoscopic endonasal procedure. Both
      surgical techniques were analyzed and compared concerning complications, surgical
      radicality, endocrinologic, and ophthalmologic outcome and recurrences in
      patients' follow-up. RESULTS: The 2 different approaches yielded similar rates of
      gross total resection (endonasal 83% [5 of 6] vs. supraorbital 87% [14 of 16]),
      near total resection (17% [1 of 6] vs. 13% [2 of 16]), and visual recovery
      (endonasal 66% [2 of 3] vs. supraorbital 60% [3 of 5]). An extension lateral to
      the internal carotid artery was noted in 81% (13 of 16) of the supraorbital cases
      and in none of the endonasal cases. Tumor volume was 14.9 cm3 (+/-8.2 cm3) for
      supraorbital tumors versus 2.1 cm3 (+/-0.8 cm3) for the endonasal approach.
      CONCLUSIONS: Both approaches provide minimally invasive surgical routes accessing
      meningiomas of the sellar region. The ideal approach should be tailored to the
      individual patient considering the tumor anatomy, lateral extension, and the
      experience of the surgeon with both surgical approaches. We suggest using the
      supraorbital approach for larger meningiomas of sellar region with far lateral
      extension or broad vascular encasement.

PMID- 28512044
TI  - Spinal Solitary Fibrous Tumor/Hemangiopericytoma: A Clinicopathologic and
      Radiologic Analysis of Eleven Cases.
AB  - OBJECTIVE: To retrospectively review the clinicopathologic features and computed
      tomography (CT) and magnetic resonance imaging (MRI) findings of spinal solitary
      fibrous tumor (SFT)/hemangiopericytoma (HPC) tumors. METHODS: Eleven patients
      with surgically and pathologically confirmed spinal SFT/HPC were enrolled. Their
      clinicopathologic data and imaging findings were retrospectively reviewed.
      RESULTS: There were 8 male and 3 female patients with a median age of 42 years
      (range, 26-65 years). Of the 11 patients, 5 were classified as grade I, 4 were
      grade II, and the remaining 2 were grade III. CT or MRI showed a well-defined (n
      = 8) or ill-defined (n = 3), oval (n = 4), irregular (n = 3), dumbbell-shaped (n
      = 3), and striped (n = 1) mass with heterogeneous (n = 10) or homogeneous (n = 1)
      density. The lesions appeared isointense (n = 4) or hypointense (n = 5) on T1
      weighted MRI and mildly hyperintense (n = 3) or hyperintense (n = 6) on T2
      weighted MRI. Bone destruction was observed in 7 cases, including osteolytic (n =
      6) and osteoblastic (n = 1) patterns. Calcification was observed in only 1 case.
      On enhanced CT/MRI, marked (n = 9), mild (n = 1) heterogeneous, and marked
      homogeneous (n = 1) enhancement were observed in this study. CONCLUSIONS: Spinal
      SFT/HPC commonly appears as a well-defined solitary mass characterized by a black
      and white appearance that is marked with heterogeneous enhancement with or
      without bone destruction.

PMID- 28512045
TI  - Early Diagnosis of Delayed Cerebral Ischemia: Possible Relevance for Inflammatory
      Biomarkers in Routine Clinical Practice?
AB  - BACKGROUND: Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH)
      is one of the main causes of neurologic deterioration. However, it frequently
      evades timely detection. Early identification and effective reversal may improve
      the clinical outcome. In this prospective study, we evaluate several serum
      inflammatory markers after aneurysmal SAH with regard to the occurrence of DCI.
      METHODS: On days 1, 4, 7, 10, and 14 after SAH, leucocyte count, C-reactive
      protein, interleukin 6, E-selectin, matrix metallopeptidase 9, intercellular
      adhesion molecule 1, and leukemia inhibitory factor were assessed in patients'
      serum samples. Using a Cox regression model (SPSS 21.0), associations of baseline
      parameters, maximum and delta (maximum minus baseline) values with occurrence of
      DCI were evaluated. RESULTS: Considering the assessed parameters, leucocyte count
      (high baseline and delta values) matches most closely with occurrence of DCI.
      Although baseline levels of C-reactive protein are also associated with
      occurrence of DCI, neither maximum (only on a borderline level) nor delta levels
      do so. CONCLUSIONS: Our data analysis identified leucocyte count as the parameter
      most likely associated with occurrence of DCI. However, because of its lack of
      specificity leucocyte count, it cannot be used as a biomarker. As hypothesized
      earlier, the results indicate a possible involvement of the inflammatory reaction
      after aneurysmal SAH in the pathomechanism of DCI.

PMID- 28512046
TI  - Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients
      Undergoing Surgery for Metastatic Brain Tumors.
AB  - OBJECTIVE: Metastatic brain tumors are the most common brain tumors in adults.
      Patients with metastatic brain tumors have poor prognoses with median survival of
      6-12 months. Seizures are a major presenting symptom and cause of morbidity and
      mortality. In this article, risk factors for the onset of preoperative seizures
      and postoperative seizure control are examined. METHODS: Adult patients who
      underwent resection of one or more brain metastases at a single institution
      between 1998 and 2011 were reviewed retrospectively. RESULTS: Of 565 patients,
      114 (20.2%) patients presented with seizures. Factors independently associated
      with preoperative seizures were preoperative headaches (P = 0.044), cognitive
      deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013),
      temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone
      involvement by tumor (P = 0.029). Factors independently associated with loss of
      seizure control after surgical resection were preoperative seizures (P = 0.001),
      temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P =
      0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P =
      0.027). At last follow-up, the majority of patients (93.8%) were seizure-free.
      Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients
      (1.41%) who did not have preoperative seizures presented with new-onset seizures
      after surgical resection of their metastases. CONCLUSIONS: The brain is a common
      site for metastases from numerous primary cancers, such as breast and lung. The
      identification of factors associated with onset of preoperative seizures as well
      as seizure control postoperatively could aid management strategies for patients
      with metastatic brain tumors. Patients with preoperative seizures who underwent
      resection tended to have good seizure control after surgery.

PMID- 28512047
TI  - Preoperative Planning of the Lateral Entry Point Is Necessary in Percutaneous L5
      Vertebroplasty.
AB  - OBJECTIVE: To compare treatment outcomes and complications between the computer
      assisted preoperative planning of lateral entry approach and the traditional
      approach for L5 percutaneous vertebroplasty. METHODS: In this prospective
      randomized clinical study performed from January 2008 to December 2014, 68
      patients scheduled for L5 percutaneous vertebroplasty were divided at random into
      group A, in which the traditional transpedicle approach was used, and group B, in
      which the computer-assisted lateral entry point approach was used. A visual
      analog scale and Oswestry Disability Index were evaluated preoperatively,
      postoperatively, and at the latest follow-up. RESULTS: Patient demographics were
      similar in the 2 groups. The mean duration of follow-up was 65 months. The mean
      distance between the entry point and the midline was 3.05 +/- 0.5 cm in group A
      and 7.04 +/- 0.7 cm in group B. The mean inclination angle measured on the
      preoperative axial image was 17.1 +/- 3.4 degrees  in group A and 41 +/- 3.8
      degrees  in group B. Clinical outcomes were comparable in the 2 groups; however,
      cement leakage was significantly greater in group A (P < 0.001). CONCLUSIONS:
      Owing to the hemispherical morphology and convergent pedicle axis of the L5
      vertebrae, a more lateral skin entry point and convergent angle of the puncture
      needle should be emphasized to reach the optimal point according to the
      preoperative assessment. The approach involving computer-assisted preoperative
      planning of the lateral entry point was associated with a higher rate of
      bilateral cement infiltration with fewer complications.

PMID- 28512048
TI  - Combined Hyperactive Dysfunction Syndrome of the Cranial Nerves: A Retrospective
      Systematic Study of Clinical Characteristics in 44 Patients.
AB  - BACKGROUND: Combined hyperactive dysfunction syndrome (HDS) is defined as the
      combination symptoms arising from overactivity in cranial nerves, specifically,
      trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia
      (GPN), without an obvious explanatory structural lesion. This study
      retrospectively analyzes the clinical characteristics of combined HDS treated
      with microvascular decompression (MVD) in a single institution. METHODS: A total
      of 1450 patients with HDS were treated with MVD in our department during a 10
      year period, among which 44 cases of combined HDS were identified. Clinical
      records and follow-ups were reviewed. RESULTS: Combined HDS comprised 3.03%
      (44/1450) of all HDS in our series, with female predominance compared with single
      HDS (P = 0.002), including combined TN-HFS (14 cases), combined TN-GPN (26
      cases), bilateral TN (2 cases), and combined TN-HFS-GPN (2 cases). The average
      age at diagnosis of patients with combined HDS (60.9 years) was significantly
      older than that of patients with single HDS (53.5 years) (P = 0.035).
      Hypertension was closely associated with the prevalence of combined HDS compared
      with single HDS (P = 0.009). The curative rate was 97.7% (43/44) after MVD, and
      the recurrence rate was 3.33%. The incidence rates of postoperative cardiac,
      pulmonary, thromboembolic, and delirium complications were higher in combined HDS
      than in single HDS (P < 0.05). CONCLUSIONS: Combined HDS is a rarely occurring
      syndrome usually observed in older females, and the most common types are
      combined TN-GPN and combined TN-HFS. Age and gender seemed to be causes for
      developing combined HDS, and MVD shows potential as a favorable treatment choice.

PMID- 28512049
TI  - Space-Occupying Tumor Bed Cysts as a Complication of Modern Treatment for High
      Grade Glioma.
AB  - BACKGROUND: The management of high-grade glioma (HGG) has been affected by recent
      landmark trials and is now more proactive. More aggressive treatment leads to
      hospitalization due to side effects, however. Space-occupying tumor bed cysts
      have been described, but not systematically assessed. We sought to analyze this
      complication in a contemporary HGG cohort. METHODS: We performed a retrospective
      review of patients with HGG treated between 2007 and 2013, identified patients
      with space-occupying tumor bed cysts, and reviewed their hospital notes for
      relevant variables. Statistical analyses were performed, and odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated. RESULTS: Tumor bed cysts
      were found in 12 of 282 patients (4%). The main symptoms were increased
      intracranial pressure (n = 11), new focal deficits (n = 6), and pseudomeningocele
      (n = 3), presenting at a median of 19 days since the last resection. Cysts were
      treated with cystoperitoneal (n = 7) and ventriculoperitoneal (n = 5) shunts,
      resulting in clinical benefit in 75% of those treated. Intraoperative opening of
      ventricles is a risk factor, with an OR of 39.339. We propose a classification
      system comprising 3 cyst types: isolated cyst, cyst with local cerebrospinal
      fluid (CSF) disturbance, and cyst with global CSF disturbance. CONCLUSIONS: In
      modern neuro-oncology, the rate of tumor bed cysts complicating HGG management
      appears stable compared with historical data. Shunt implantation is feasible and
      effective. We propose a classification system as a common data element for
      comparison across future studies.

PMID- 28512050
TI  - Assessing the Role of Preoperative Embolization in the Surgical Management of
      Cerebral Arteriovenous Malformations.
AB  - BACKGROUND: Preoperative embolization is established as an advantageous adjunct
      in multimodality treatment of cerebral arteriovenous malformations (AVMs).
      However, the benefit of preoperative embolization in AVMs with favorable surgical
      risk profile is debatable, because it has yet to be supported by evidence in
      comparative studies. In this study, we assessed outcome of surgically treated
      patients in a comparative setting. METHODS: Our institutional AVM database of
      retrospectively and prospectively collected data between 1990 and 2015 was
      reviewed. Patients with complete clinical data who underwent surgical resection
      for AVMs were included. We performed a 1:1 ratio propensity score match for
      baseline variables that differed between patients with or without preoperative
      embolization. Differences in surgical risk and outcomes were evaluated between
      these 2 groups. RESULTS: AVM size, eloquence, deep drainage, middle cerebral
      artery feeder, and ruptured presentation differed significantly between the 2
      groups. Forty-eight patients without preoperative embolization were matched to 48
      with embolization, with no significant differences in baseline variables or AVM
      characteristics between the 2 groups. We found no significant differences in AVM
      obliteration and postoperative modified Rankin Scale (mRS) score between
      embolized and nonembolized patients, respectively. Change in mRS score from
      preoperative score was also not significant, although more embolized patients had
      a decline in mRS score. Secondary outcome measures including duration of surgery
      (P = 0.172), intraoperative bleeding (P = 0.280), duration of hospitalization (P
      = 0.368), and postoperative symptoms were also similar between both groups.
      CONCLUSIONS: Our data do not support substantial benefit of preoperative
      embolization for patients with a favorable surgical risk profile. Because of
      risks and costs with this intervention, the prudent use of preoperative
      embolization should be individually considered.

PMID- 28512052
TI  - Cystic Dilation of the Ventriculus Terminalis: Report of 6 Surgical Cases Treated
      with Cyst-Subarachnoid Shunting Using a T-Catheter.
AB  - BACKGROUND: Cystic dilation of the ventriculus terminalis (CDVT) is a rare
      anatomic variation that and may become symptomatic. Literature regarding CDVT is
      limited, and thus the clinical characteristics and management strategy of CDVT
      are unclear. Here we report 6 cases of CDVT seen in our institution, and provide
      a review of the current literature. METHODS: The study cohort comprised 6
      patients with CDVT seen at Beijing Tiantan Hospital between September 2010 and
      June 2015. All 6 patients were managed surgically. Data on age, sex, clinical
      presentation, radiologic features, operative methods, and surgical outcomes were
      reviewed retrospectively. We evaluated the clinical outcomes and postoperative
      radiologic changes of these patients and compared them with findings of similar
      previous reports. RESULTS: All 6 patients were female, with a median age of 50.0
      years (interquartile range [IQR], 25.8-54.0 years). Surgical management of cyst
      subarachnoid shunting using T-catheter after myelotomy was successfully performed
      in all patients. During an average follow-up of 41 months, relief of clinical
      symptoms, especially low-back pain and sciatica, were observed in all 6 patients.
      No patients experienced symptom recurrence during follow-up, and postoperative
      magnetic resonance imaging revealed no regrowth of the lesion. Patients with
      focal neurologic deficits and sphincter disorders also achieved symptom relief
      from the procedure. CONCLUSIONS: CDVT is an extremely rare cause of conus
      medullaris syndrome with an unclear treatment strategy. Our successful surgical
      management of 6 cases through cystic-subarachnoid shunting using a T-catheter for
      CDVT drainage provides a potential option for treating CDVT.

PMID- 28512051
TI  - Membranectomy in Chronic Subdural Hematoma: Meta-Analysis.
AB  - OBJECTIVE: Initial management strategies of chronic subdural hematoma (cSDH) are
      controversial and range from bedside twist-drill or burr-hole drainage to
      craniotomy with membranectomy (CWM). We aim to 1) perform a meta-analysis of the
      available data on the outcomes of CWM for treatment of cSDH in published English
      language literature and 2) evaluate collective outcomes of CWM with respect to
      morbidity, mortality, and recurrence rates. METHODS: A search of English-language
      literature performed in PubMed, Ovid, and Cochrane databases using key words
      ("subdural hematoma" or "chronic subdural hematoma") and ("membrane" or
      "membranectomy") from inception to December 2016 was conducted. Studies reporting
      outcomes of CWM in cSDH were included. Mortality, morbidity, follow-up duration,
      and recurrence rate data were extracted and analyzed. Pooled estimates and
      confidence intervals (CIs) were calculated for all outcomes using a random
      effects model. RESULTS: Of 301 articles found, 17 articles containing 5369
      patients met our eligibility criteria. Mean follow-up duration ranged from 1-30.8
      months. Collective mean mortality and morbidity rates were 3.7% and 6.9%,
      respectively (95% CI 2-5.4% and 2.1-11.6%; P < 0.001 and P = 0.004). The
      collective mean recurrence rate was 7.6% (95% CI: 5%-10.2%; P < 0.001).
      CONCLUSIONS: Clinical data on outcomes of CWM in cSDH are limited to single
      institutional analyses, with considerable variation in recurrence rates and
      follow-up time. The rates we reported are comparable with the 5% mortality and 3%
      12% morbidity rates and lower than the 10%-21% recurrence rate in the literature
      for burr holes or craniotomy without membranectomy. This meta-analysis provides
      an in-depth analysis of available data and reviews reported outcomes.

PMID- 28512054
TI  - Synthesis and characterization of psyllium seed mucilage grafted with N,N
      methylene bisacrylamide.
AB  - Psyllium seed polysaccharide was modified to investigate its use as
      multifunctional pharmaceutical excipient. The objective of this study was
      isolation of psyllium seed polysaccharide and crosslinking with acrylic acid
      using N,N-methylene bisacrylamide and its characterization. Acrylic acid was used
      as monomer and ammonium persulfate as initiator. A full factorial design was
      employed to optimize the crosslinking. The modified polysaccharide was
      characterized by FTIR, DSC, PXRD, loss on drying, pH, viscosity, micromeritics
      properties and swelling studies in 0.1N HCl, 0.5N NaOH, phosphate buffer pH 6.8.
      It was observed that swelling of crosslinked polysaccharide increased with
      decreased concentration of monomer and increasing concentration of crosslinker.
      Greater degree of grafting was observed with increase in crosslinker and monomer
      concentration. Dispersions of 1% w/v of PPS and APPS show pseudoplastic behavior.
      No clinical signs of toxicity were evident in repeat dose toxicity studies
      conducted in rats. Administration of up to 350mg/kg/day of APPS was well
      tolerated by the animals. Modification of psyllium via graft copolymerization and
      network formation with the crosslinker, improved the property profile and utility
      of psyllium polysaccharide. The modified polysaccharide can be used for designing
      controlled release drug delivery systems due to its swelling ability.

PMID- 28512053
TI  - Effect of chitosan and coagulation factors on the wound repair phenotype of
      bioengineered blood clots.
AB  - Controlling the blood clot phenotype in a surgically prepared wound is an
      evolving concept in scaffold-guided tissue engineering. Here, we investigated the
      effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation
      factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory
      factors released by blood clots. We tested the hypothesis that 80% DDA chitosan
      specifically enhances leukotriene B4 (LTB4) production. Human or rabbit whole
      blood was combined with isotonic chitosan solutions, coagulation factors, or
      lipopolysaccharide, cultured in vitro at 37 degrees C, and after 4hours the serum
      was assayed for LTB4 or inflammatory factors. Only 80% DDA chitosan clots
      produced around 15-fold more LTB4 over other clots including 95% DDA chitosan
      clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots
      produced very low type I cytokines compared to lipopolysaccharide clots, with
      even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots.
      Coagulation factors had no detectable effect on clot phenotype. Conclusion In
      blood clots from healthy individuals, 80% DDA chitosan has a unique influence of
      inducing more LTB4, a potent neutrophil chemoattractant, with similar production
      of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots.

PMID- 28512055
TI  - First plasma and tissue pharmacokinetic study of the YSNSG cyclopeptide, a new
      integrin antagonist, using microdialysis.
AB  - The YSNSG peptide is a synthetic peptide targeting alphavbeta3 integrin. This
      peptide exhibits promising activity in vitro and in vivo against melanoma. To
      determine pharmacokinetic parameters and predictive active doses in the central
      nervous system (CNS) and subcutaneous tissue (SC), we conducted microdialysis
      coupled with pharmacokinetic modeling and Monte Carlo simulation. After a
      recovery period of surgical procedures, a microdialysis probe was inserted in the
      caudate and in subcutaneous tissue. Plasma samples and dialysates collected 5h
      after YSNSG intravenous administration (10mg/kg) were analyzed by UPLC-MS/MS. A
      nonlinear mixed-effect modeling approach implemented in Monolix(r) 2016R1 was
      performed. Model selection and evaluation were based on the usual diagnostic
      plot, precision and information criteria. The primary plasma and tissue
      pharmacokinetic parameters were comparable with those of other integrin
      antagonists, such as cilengitide or ATN-161. Tissue/plasma and brain/plasma area
      under the curve (AUC) ratio were 66.2+/-21.6% and 3.6+/-4.7%, respectively. Two
      models of 2-compartments with an additional microdialysis compartment,
      parameterized as rate constants (k for elimination, k12/k21 and k13/k31 for
      distribution) and volumes (central V1 and peripheral microdialysis compartment
      V3) with zero-order input were selected to describe the dialysate concentrations
      in CNS and SC. The inter-individual variability (IIV) was described by
      exponential terms, and residual variability was described by a combined additive
      and proportional error model. Individual AUC (plasma and tissues) values were
      derived for each animal using the Empirical-Bayes-Estimates of the individual
      parameters. The regimens needed to achieve an in vitro predetermined target
      concentration in tissues were studied by Monte Carlo simulations using Monolix(r)
      2016R1. YSNSG pharmacokinetic parameters show promising results in terms of
      subcutaneous disposition. Further investigations into such processes as
      encapsulation and intratumoral disposition are currently being conducted.

PMID- 28512056
TI  - Combined proportional and additive residual error models in population
      pharmacokinetic modelling.
AB  - INTRODUCTION: In pharmacokinetic modelling, a combined proportional and additive
      residual error model is often preferred over a proportional or additive residual
      error model. Different approaches have been proposed, but a comparison between
      approaches is still lacking. METHODS: The theoretical background of the methods
      is described. Method VAR assumes that the variance of the residual error is the
      sum of the statistically independent proportional and additive components; this
      method can be coded in three ways. Method SD assumes that the standard deviation
      of the residual error is the sum of the proportional and additive components.
      Using datasets from literature and simulations based on these datasets, the
      methods are compared using NONMEM. RESULTS: The different coding of methods VAR
      yield identical results. Using method SD, the values of the parameters describing
      residual error are lower than for method VAR, but the values of the structural
      parameters and their inter-individual variability are hardly affected by the
      choice of the method. CONCLUSION: Both methods are valid approaches in combined
      proportional and additive residual error modelling, and selection may be based on
      OFV. When the result of an analysis is used for simulation purposes, it is
      essential that the simulation tool uses the same method as used during analysis.

PMID- 28512057
TI  - Normative morphometric data for cerebral cortical areas over the lifetime of the
      adult human brain.
AB  - Proper normative data of anatomical measurements of cortical regions, allowing to
      quantify brain abnormalities, are lacking. We developed norms for regional
      cortical surface areas, thicknesses, and volumes based on cross-sectional MRI
      scans from 2713 healthy individuals aged 18 to 94 years using 23 samples provided
      by 21 independent research groups. The segmentation was conducted using
      FreeSurfer, a widely used and freely available automated segmentation software.
      Models predicting regional cortical estimates of each hemisphere were produced
      using age, sex, estimated total intracranial volume (eTIV), scanner manufacturer,
      magnetic field strength, and interactions as predictors. The explained variance
      for the left/right cortex was 76%/76% for surface area, 43%/42% for thickness,
      and 80%/80% for volume. The mean explained variance for all regions was 41% for
      surface areas, 27% for thicknesses, and 46% for volumes. Age, sex and eTIV
      predicted most of the explained variance for surface areas and volumes while age
      was the main predictors for thicknesses. Scanner characteristics generally
      predicted a limited amount of variance, but this effect was stronger for
      thicknesses than surface areas and volumes. For new individuals, estimates of
      their expected surface area, thickness and volume based on their characteristics
      and the scanner characteristics can be obtained using the derived formulas, as
      well as Z score effect sizes denoting the extent of the deviation from the
      normative sample. Models predicting normative values were validated in
      independent samples of healthy adults, showing satisfactory validation R2.
      Deviations from the normative sample were measured in individuals with mild
      Alzheimer's disease and schizophrenia and expected patterns of deviations were
      observed.

PMID- 28512058
TI  - Downregulation of miR-224 and let-7i contribute to cell survival and
      chemoresistance in chronic myeloid leukemia cells by regulating ST3GAL IV
      expression.
AB  - Acquired resistance to imatinib is frequently associated with poor clinical
      outcome of chronic myeloid leukemia (CML) patient. To date, evidence indicates
      that protein glycosylation and its upstream regulators might be implicated in
      tumorigenesis and chemoresistance occurrence. In current study we initially
      explored N-glycan profiles on the surface of CML cell lines and bone marrow
      mononuclear cells (BMMC) of CML patients by using mass spectrometry (MS)
      analysis. An elevated sialylation was detected in K562R cells (CML cells with
      imatinib resistance phenotype) compare to K562 cells. By quantitative real time
      PCR (qRT-PCR) and western blotting analysis we observed that imatinib resistant
      K562R cells exhibited marked high levels of CMP-N-acetylneuraminate-beta
      galactosamide-alpha-2,3-sialyltransferase (ST3Gal IV) as compared to imatinib
      sensitive K562 cells. Further studies revealed that manipulated expression of
      ST3GAL IV led to the significant alterations of cell cycle distribution,
      apoptotic signal, cell proliferation and the effectiveness of imatinib treatment.
      Using microRNA array, miRNA database searching and luciferase reporter assay, we
      identified that miR-224 and let-7i directly regulate the expression of ST3GAL IV
      gene. Moreover, engineered expression of miR-224 and let-7i in K562 and K562R
      cells could significantly affect ST6Gal IV-induced proliferation rate and drug
      resistance. Thus we propose that miR-224 and let-7i regulate the proliferation
      and chemosensitivity of CML cells probably via targeting ST3GAL IV.

PMID- 28512059
TI  - Genome-scale metabolic network of Cordyceps militaris useful for comparative
      analysis of entomopathogenic fungi.
AB  - The first genome-scale metabolic network of Cordyceps militaris (iWV1170) was
      constructed representing its whole metabolisms, which consisted of 894
      metabolites and 1,267 metabolic reactions across five compartments, including the
      plasma membrane, cytoplasm, mitochondria, peroxisome and extracellular space. The
      iWV1170 could be exploited to explain its phenotypes of growth ability,
      cordycepin and other metabolites production on various substrates. A high number
      of genes encoding extracellular enzymes for degradation of complex carbohydrates,
      lipids and proteins were existed in C. militaris genome. By comparative genome
      scale analysis, the adenine metabolic pathway towards putative cordycepin
      biosynthesis was reconstructed, indicating their evolutionary relationships
      across eleven species of entomopathogenic fungi. The overall metabolic routes
      involved in the putative cordycepin biosynthesis were also identified in C.
      militaris, including central carbon metabolism, amino acid metabolism (glycine, l
      glutamine and l-aspartate) and nucleotide metabolism (adenosine and adenine).
      Interestingly, a lack of the sequence coding for ribonucleotide reductase
      inhibitor was observed in C. militaris that might contribute to its over
      production of cordycepin.

PMID- 28512060
TI  - Characterization and phylogenetic analysis of complete mitochondrial genomes for
      two desert cyprinodontoid fishes, Empetrichthys latos and Crenichthys baileyi.
AB  - The Pahrump poolfish (Empetrichthys latos) and White River springfish
      (Crenichthys baileyi) are small-bodied teleost fishes (order Cyprinodontiformes)
      endemic to the arid Great Basin and Mojave Desert regions of western North
      America. These taxa survive as small, isolated populations in remote streams and
      springs and evolved to tolerate extreme conditions of high temperature and low
      dissolved oxygen. Both species have experienced severe population declines over
      the last 50-60years that led to some subspecies being categorized with protected
      status under the U.S. Endangered Species Act. Here we report the first sequencing
      of the complete mitochondrial DNA genomes for both E. l. latos and the moapae
      subspecies of C. baileyi. Complete mitogenomes of 16,546bp nucleotides were
      obtained from two E. l. latos individuals collected from introduced populations
      at Spring Mountain Ranch State Park and Shoshone Ponds Natural Area, Nevada, USA,
      while a single mitogenome of 16,537bp was sequenced for C. b. moapae. The
      mitogenomes of both species contain 13 protein-encoding genes, twenty-two tRNAs,
      and two rRNAs (12S and 18S) following the syntenic arrangement typical of
      Actinopterygiian fish mitogenomes, as well as D-loop control regions of 858bp for
      E. latos and 842bp for C. baileyi moapae. The two E. latos individuals exhibited
      only 0.0181% nucleotide sequence divergence across the entire mitogenome,
      implying little intraspecific mtDNA genetic variation. Comparative phylogenetic
      analysis of the poolfish and springfish mitochondrial genomes to available
      mitogenomes of other Cyprinodontoid fishes confirmed the close relationship of
      these oviparous Empetrichthys and Crenichthys genera to the viviparous goodeid
      fishes of central Mexico, and showed the combined clade of these fishes to be a
      sister group to the Profundulidae killifishes. Despite several significant life
      history and morphological differences between the Empetrichthyinae and Goodienae,
      estimates of evolutionary genetic distances using two partial regions of mtDNA
      point to inclusion of the Empetrichthys and Crenichthys genera within the family
      Goodeidae along with the goodeid fishes of central Mexico.

PMID- 28512061
TI  - Genetic variants in autophagy associated genes are associated with DNA damage
      levels in Chinese population.
AB  - Autophagy associated genes (ATGs) played an important role in the repair process
      of DNA damage and decreased autophagy may weaken the repair process and aggravate
      DNA damage. Based on this, we hypothesized that DNA damage levels might be
      modified by genetic variants in autophagy associated genes. In order to validate
      our hypothesis, 307 subjects were recruited from three different cities (Zhuhai,
      Wuhan and Tianjin) in China. Demographic data, individual 24-h PM2.5 exposure and
      peripheral blood DNA damage levels were also detected. Seven potentially
      functional polymorphisms in four essential autophagy associated genes (ATG5,
      ATG7, ATG8 and ATG13) were screened to evaluate the relationship between the
      polymorphisms of autophagy associated genes and DNA damage levels. This
      association was assessed by using multivariable linear regression model, age,
      sex, smoke and PM2.5 exposure levels were adjusted in each city. We found that
      rs12599322 in ATG8 (A>G, beta=0.263, 95% CI: 0.108-0.419, P=8.98*10-4) and
      rs7484002 in ATG13 (A>G, beta=0.396, 95% CI: 0.085-0.708, P=0.013) were
      significantly associated with higher DNA damage levels. Furthermore, functional
      annotations showed that both rs12599322 and rs7484002 located at transcription
      factor binding sites (TFBS), indicating that they could regulate the expression
      of related genes through TF regulation. Following allelic trend analysis revealed
      that the DNA damage levels were significantly aggravated with the increasing
      number of risk variants in autophagy associated genes (P for trend: 8.09*10-5).
      Our findings suggested that the polymorphisms in ATGs may influence DNA damage
      levels in one of the Chinese population.

PMID- 28512062
TI  - Hsa-miR-513b-5p suppresses cell proliferation and promotes P53 expression by
      targeting IRF2 in testicular embryonal carcinoma cells.
AB  - Previous studies have reported the miR-513b is located on the X chromosome and is
      preferentially expressed in testis. However, the underlying mechanisms of miR
      513b involved in spermatogenesis remains unknown. In this study, we found that
      hsa-miR-513b-5p was highly expressed in the testes of infertile males with
      maturation arrest compared with normal controls. Overexpression of hsa-miR-513b
      5p suppressed testicular embryonal carcinoma (NT2) cell proliferation and induced
      apoptosis in vitro, whereas silencing of hsa-miR-513b-5p reversed these effects.
      In addition, we found that interferon regulatory transcription factor 2 (IRF2)
      was a direct and functional target of hsa-miR-513b-5p. Silencing of endogenous
      IRF2 enhanced hsa-miR-513b-5p-mediated effects on cell proliferation in NT2
      cells, whereas overexpression of IRF2 reversed these effects. Moreover,
      immunoblotting showed that overexpression of hsa-miR-513b-5p or silencing of
      endogenous IRF2 could promote the expression of P53. Moreover, overexpression of
      hsa-miR-513b-5p in the absence of p53 could also induce cell apoptosis. Together,
      our results suggest that hsa-miR-513b-5p suppresses NT2 cell proliferation and
      promotes P53 protein expression by targeting IRF2, and abnormal testicular hsa
      miR-513b-5p expression may contribute to maturation arrest.

PMID- 28512064
TI  - Familial lumps of the lower jaw.

PMID- 28512065
TI  - Long-Term Functional and Psychosocial Outcomes After Hypoxic-Ischemic Brain
      Injury: A Case-Controlled Comparison to Traumatic Brain Injury.
AB  - BACKGROUND: Despite the increasing rate of survival from hypoxic-ischemic brain
      injury (HIBI), there is a paucity of evidence on the long-term functional
      outcomes after inpatient rehabilitation among these nontrauma patients compared
      to patients with traumatic brain injury (TBI). OBJECTIVES: To compare functional
      and psychosocial outcomes of patients with HIBI to those of case-matched patients
      with TBI 4-11 years after brain insult. DESIGN: Retrospective, matched case
      controlled study. METHODS: Data at the time of rehabilitation admission and
      discharge were collected as part of a larger acquired brain injury (ABI) database
      at Toronto Rehabilitation Institute (TRI) between 1999 and 2009. This study
      consisted of 11 patients with HIBI and 11 patients with TBI that attended the
      neuro-rehabilitation day program at TRI during a similar time frame and were
      matched on age, admission Functional Independence Measure (FIM) scores, and acute
      care length of stay (ALOS). At 4-11 years following brain insult, patients were
      reassessed using the FIM, Disability Rating Scale (DRS), Personal Health
      Questionnaire Depression Scale (PHQ-9), and the Mayo-Portland Adaptability
      Inventory 4 (MPAI-4). RESULTS: At follow-up, patients with HIBI had significantly
      lower FIM motor and cognitive scores than patients with TBI (75.3 +/- 20.6 versus
      88.1 +/- 4.78, P < .05, and 25.5 +/- 5.80 versus 32.7 +/- 2.54, P <.05,
      respectively) despite having a similar time frame postinsult (ie, 4-11 years). In
      addition, there were significant differences in motor and total FIM change from
      admission to follow-up between HIBI and TBI patients (P < .05). Patients with
      HIBI also had significantly lower scores on the DRS, PHQ-9, and total MPAI-4 at
      follow-up (P < .05). CONCLUSIONS: The study results suggest that patients with
      HIBI achieve less long-term functional improvements compared to patients with
      TBI. Further research is warranted to compare the components of inpatient
      rehabilitation while adjusting for demographics and clinical characteristics
      between these 2 groups of patients. LEVEL OF EVIDENCE: III.

PMID- 28512063
TI  - Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on
      T2-mapping: is it possible to comprehensively assess knee cartilage composition
      in one post-contrast MR examination at 3 Tesla?
AB  - OBJECTIVE: To evaluate the possibility of assessing knee cartilage with T2
      mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of
      cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). DESIGN:
      T2 mapping was performed in 10 healthy volunteers at baseline; directly after
      baseline; after 10 min of cycling; and after 90 min delay, and in 16
      osteoarthritis patients before and after intravenous administration of a double
      dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol
      elements. Differences in T2 relaxation times between each timepoint and baseline
      were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed
      rank tests and the smallest detectable change (SDC). RESULTS: After cycling, a
      significant change in T2 relaxation times was found in the lateral weight-bearing
      tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were
      found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the
      lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of
      interests (ROIs), absolute differences were small and lower than the
      corresponding SDCs. T2-mapping after contrast administration only showed
      statistically significantly lower T2 relaxation times in the medial posterior
      femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. CONCLUSION:
      Because dGEMRIC protocol elements resulted in only small differences in T2
      relaxation times that were not consistent and lower than the SDC in the majority
      of regions, our results suggest that T2-mapping and dGEMRIC can be performed
      reliably in a single imaging session to assess cartilage biochemical composition
      in knee osteoarthritis (OA) at 3 T.

PMID- 28512066
TI  - Use of Electroencephalography Brain-Computer Interface Systems as a
      Rehabilitative Approach for Upper Limb Function After a Stroke: A Systematic
      Review.
AB  - BACKGROUND: Brain-computer interface (BCI) systems have been suggested as a
      promising tool for neurorehabilitation. However, to date, there is a lack of
      homogeneous findings. Furthermore, no systematic reviews have analyzed the degree
      of validation of these interventions for upper limb (UL) motor rehabilitation
      poststroke. OBJECTIVES: The study aims were to compile all available studies that
      assess an UL intervention based on an electroencephalography (EEG) BCI system in
      stroke; to analyze the methodological quality of the studies retrieved; and to
      determine the effects of these interventions on the improvement of motor
      abilities. TYPE: This was a systematic review. LITERATURE SURVEY: Searches were
      conducted in PubMed, PEDro, Embase, Cumulative Index to Nursing and Allied
      Health, Web of Science, and Cochrane Central Register of Controlled Trial from
      inception to September 30, 2015. METHODOLOGY: This systematic review compiles all
      available studies that assess UL intervention based on an EEG-BCI system in
      patients with stroke, analyzing their methodological quality using the Critical
      Review Form for Quantitative Studies, and determining the grade of recommendation
      of these interventions for improving motor abilities as established by the Oxford
      Centre for Evidence-based Medicine. The articles were selected according to the
      following criteria: studies evaluating an EEG-based BCI intervention; studies
      including patients with a stroke and hemiplegia, regardless of lesion origin or
      temporal evolution; interventions using an EEG-based BCI to restore functional
      abilities of the affected UL, regardless of the interface used or its combination
      with other therapies; and studies using validated tools to evaluate motor
      function. SYNTHESIS: After the literature search, 13 articles were included in
      this review: 4 studies were randomized controlled trials; 1 study was a
      controlled study; 4 studies were case series studies; and 4 studies were case
      reports. The methodological quality of the included papers ranged from 6 to 15,
      and the level of evidence varied from 1b to 5. The articles included in this
      review involved a total of 141 stroke patients. CONCLUSIONS: This systematic
      review suggests that BCI interventions may be a promising rehabilitation approach
      in subjects with stroke. LEVEL OF EVIDENCE: II.

PMID- 28512067
TI  - Optimal implantation is the way to prevent scaffold thrombosis: a hypothesis to
      be tested.

PMID- 28512068
TI  - Potentially increased incidence of scaffold thrombosis in patients treated with
      Absorb BVS who terminated DAPT before 18 months.
AB  - AIMS: The aim of this study was to investigate the impact of dual antiplatelet
      therapy (DAPT) termination on late and very late scaffold thrombosis (ScT) in
      patients treated with the Absorb bioresorbable vascular scaffold (BVS). METHODS
      AND RESULTS: Data from the registries of three centres were pooled (808
      patients). To investigate the effect of DAPT termination on ScT after a minimum
      of six months, we selected a subgroup ("DAPT study cohort" with 685 patients)
      with known DAPT status >6 months and excluded the use of oral anticoagulants and
      early ScT. In this cohort, definite/probable ScT incidence for the period on DAPT
      was compared to ScT incidence after DAPT termination. ScT incidence was 0.83
      ScT/100 py with 95% confidence interval (CI): 0.34-1.98. After DAPT termination,
      the incidence was higher (1.77/100 py; 95% CI: 0.66-4.72), compared to the
      incidence on DAPT (0.26/100 py, 95% CI: 0.04-1.86; p=0.12) and increased within
      the month after DAPT termination (6.57/100 py, 95% CI: 2.12-20.38; p=0.01). No
      very late ScT occurred in patients who continued on DAPT for a minimum of 18
      months. CONCLUSIONS: The incidence of late and very late definite/probable ScT
      was acceptable. The incidence was low while on DAPT but potentially higher when
      DAPT was terminated before 18 months.

PMID- 28512069
TI  - Optical coherence tomography findings: insights from the "randomised multicentre
      trial investigating angiographic outcomes of hybrid sirolimus-eluting stents with
      biodegradable polymer compared with everolimus-eluting stents with durable
      polymer in chronic total occlusions" (PRISON IV) trial.
AB  - AIMS: The PRISON IV trial investigated the next-generation sirolimus-eluting
      stent (SES) with ultra-thin struts and biodegradable polymer against the second
      generation everolimus-eluting stent (EES) with thin struts and durable polymer in
      patients with successfully recanalised chronic total occlusions (CTO). In this
      study, we examined the secondary optical coherence tomography endpoints. METHODS
      AND RESULTS: The main PRISON IV trial randomised 330 patients to either SES or
      EES. At nine months, 281 (85%) patients underwent repeat angiography. Of these,
      60 consecutive patients received optical coherence tomography divided over both
      stent groups. The mean number of struts analysed was 750+/-337 and 633+/-358 in
      SES and EES patients, respectively (p=0.07). The minimal lumen area, minimal
      stent area, maximal neointima area and neointimal thickness were comparable
      between the groups (4.8+/-2.1 and 4.4+/-1.5 mm2; 5.3+/-1.8 and 5.3+/-1.4 mm2;
      2.5+/-2.0 and 2.2+/-1.5 mm2; 0.7+/-1.7 and 0.4+/-0.2 mm). The percentage of
      uncovered struts was higher with EES (6.2+/-7.5% and 11.9+/-13.4%, p=0.04),
      whereas the percentage of malapposed struts and mean number of coronary
      evaginations were significantly higher with SES (2.9+/-4.0% and 1.2+/-2.4%,
      p=0.02; 18.5+/-17.7 and 5.3+/-3.1, p=0.004). CONCLUSIONS: The optical coherence
      tomography findings of this substudy demonstrated improved strut coverage with
      ultra-thin strut SES with bioresorbable polymer compared to thin-strut EES with
      durable polymer in CTO. On the other hand, SES showed a higher rate of stent
      strut malappositon and coronary evaginations. The clinical relevance of these
      findings remains to be demonstrated.

PMID- 28512070
TI  - Very late scaffold thrombosis: is prolonged DAPT the answer?

PMID- 28512071
TI  - Ethical and legal challenges of vaccines and vaccination: Reflections.
AB  - Vaccines and vaccination have emerged as key medical scientific tools for
      prevention of certain diseases. Documentation of the history of vaccination shows
      that the initial popular resistance to universal vaccination was based on false
      assumptions and eventually gave way to acceptance of vaccines and trust in their
      ability to save lives. The successes of the global eradication of smallpox, and
      now of polio, have only strengthened the premier position occupied by vaccines in
      disease prevention. However, the success of vaccines and public trust in their
      ability to eradicate disease are now under challenge, as increasing numbers of
      people refuse vaccination, questioning the effectiveness of vaccines and the need
      to vaccinate.

PMID- 28512072
TI  - Lessons learnt in Japan from adverse reactions to the HPV vaccine: a medical
      ethics perspective.
AB  - The human papillomavirus (HPV) vaccine has been linked to a number of serious
      adverse reactions. The range of symptoms is diverse and they develop in a multi
      layered manner over an extended period of time. The argument for the safety and
      effectiveness of the HPV vaccine overlooks the following flaws: (i) no
      consideration is given to the genetic basis of autoimmune diseases, and arguments
      that do not take this into account cannot assure the safety of the vaccine; (ii)
      the immune evasion mechanisms of HPV, which require the HPV vaccine to maintain
      an extraordinarily high antibody level for a long period of time for it to be
      effective, are disregarded; and (iii) the limitations of effectiveness of the
      vaccine. We also discuss various issues that came up in the course of developing,
      promoting and distributing the vaccine, as well as the pitfalls encountered in
      monitoring adverse events and epidemiological verification.

PMID- 28512073
TI  - Identifying ethical issues in the development of vaccines and in vaccination.
AB  - Vaccines are a widely accepted public health intervention. They are also a
      profitable tool for pharmaceutical companies manufacturing vaccines. There are
      many vaccines in the pipeline, for various diseases, or as combination vaccines
      for several diseases. However, there is also a growing concern about vaccines and
      the manner in which they are developed and approved by the authorities. Approvals
      are fast tracked and adverse events and serious adverse events following
      vaccination are seldom reported once the vaccine gets its marketing approval.
      Thus, vaccines have been clouded with many controversies and their use as a
      public health tool to prevent diseases is constantly under challenge.

PMID- 28512074
TI  - An idea whose time has come: Compensation for vaccine-related injuries and death
      in India.
AB  - This paper emphasises the urgent need for a compensation policy for those
      affected by adverse events following immunisation in India. In the absence of
      such a mechanism in the country, people claim compensation by taking recourse to
      tort law and have to face the ensuing uncertainty and challenges with regard to
      the award of compensation. The paper argues that people should be provided
      compensation in the event of death and serious adverse events following
      compulsory immunisation, irrespective of whether there is a causal association
      between the adverse event and the vaccine, on the basis of no fault compensation.

PMID- 28512075
TI  - Public trust in vaccination: an analytical framework.
AB  - While vaccination is one of the most successful public health interventions,
      there has always been a parallel movement against vaccines. Apart from scientific
      factors, the uptake of vaccinations is influenced by historical, political,
      sociocultural and economic factors. In India, the health system is struggling
      with logistical weaknesses in taking vaccination to the remotest corners; while
      on the other hand, some people in places where vaccination is available resist
      it. Unwillingness to be vaccinated is a growing problem in the developed world.
      This trend is gradually emerging in several parts of India as well. Other
      factors, such as heightened awareness of the profit motives of the vaccine
      industry, conflicts of interest among policy-makers, and social, cultural and
      religious considerations have eroded the people's trust in vaccination. This
      paper develops an analytical framework to assess trust in vaccination. The
      framework considers trust in vaccination from four perspectives - trust in the
      health system, the vaccine policy, vaccination providers and specific vaccines.
      The framework considers specific issues involved in vaccination trust, including
      the increasing scepticism towards medical technology, perceptions of conflicts of
      interest in the vaccine policy, and of lack of transparency and openness, the
      presence of strong alternative schools of thought, influence of the social media.
      The paper will conclude by arguing that engaging with communities and having a
      dialogue about the vaccination policy is an ethical imperative.

PMID- 28512076
TI  - Considering the "public" in public health: popular resistance to the Smallpox
      Eradication Programme in India.
AB  - Public health initiatives, including large-scale vaccination and disease
      eradication programmes, regularly pit the rights of the individual against
      broader benefits to society. At times, the public resists such initiatives, with
      the World Health Organisation's Smallpox Eradication Programme (SEP) in India
      being a case in point. Here, we critically investigate resistance to smallpox
      vaccines in India and argue that while the SEP successfully eradicated a global
      killer; individuals were stripped of human rights through coercion, forcible
      vaccination and quarantine. In many cases, resistance to vaccination was linked
      to deep-rooted social, cultural and religious beliefs. Critical points made in
      this paper are applicable to contemporary discussions on required vaccinations,
      quarantine during the outbreak of diseases and the current campaign to eradicate
      polio.

PMID- 28512077
TI  - Vaccine delivery to disease control: a paradigm shift in health policy.
AB  - India's Universal Immunisation Programme (UIP) has resulted in the creation of
      infrastructure, human resources and systems for the procurement and delivery of
      vaccines. Recently, new vaccines have been added and there are plans for the
      introduction of more. However, the outcomes in terms of reduction of the diseases
      for which the vaccines are being administered remain ambiguous. This is evident
      from the persistent health issues that children continue to experience, despite
      immunisation. This situation raises a fundamental ethical question for public
      health: vaccinations are one of the tools of disease control, but are they
      properly aligned to the control of disease so as to produce the expected public
      health utility or benefit?

PMID- 28512078
TI  - Is MCI over emphasising publication for promotion of medical teachers?
AB  - Over the past year, there has been constant debate in various journals on the
      circular issued by the Medical Council of India (MCI) in September 2015,
      regarding the requirements for promotion of teaching faculty. The lack of a time
      bound promotion system of medical faculty results in higher stress,
      dissatisfaction, lower productivity and quality of life and work. The critics
      have highlighted several issues in assessment of publication for teacher's
      promotion, eg the exclusion of publications in "electronic-only" journals,
      awarding points only to "original research" papers and first or second authors,
      listing of indexing databases for journals, categorising journals as national or
      international.

PMID- 28512079
TI  - Crowdsourced Identification of Possible Allergy-Associated Factors: Automated
      Hypothesis Generation and Validation Using Crowdsourcing Services.
AB  - BACKGROUND: Hypothesis generation is an essential task for clinical research, and
      it can require years of research experience to formulate a meaningful hypothesis.
      Recent studies have endeavored to apply crowdsourcing to generate novel
      hypotheses for research. In this study, we apply crowdsourcing to explore
      previously unknown allergy-associated factors. OBJECTIVE: In this study, we aimed
      to collect and test hypotheses of unknown allergy-associated factors using a
      crowdsourcing service. METHODS: Using a series of questionnaires, we asked
      crowdsourcing participants to provide hypotheses on associated factors for seven
      different allergies, and validated the candidate hypotheses with odds ratios
      calculated for each associated factor. We repeated this abductive validation
      process to identify a set of reliable hypotheses. RESULTS: We obtained two
      primary findings: (1) crowdsourcing showed that 8 of the 13 known hypothesized
      allergy risks were statically significant; and (2) among the total of 157
      hypotheses generated by the crowdsourcing service, 75 hypotheses were
      statistically significant allergy-associated factors, comprising the 8 known
      risks and 53 previously unknown allergy-associated factors. These findings
      suggest that there are still many topics to be examined in future allergy
      studies. CONCLUSIONS: Crowdsourcing generated new hypotheses on allergy
      associated factors. In the near future, clinical trials should be conducted to
      validate the hypotheses generated in this study.

PMID- 28512080
TI  - Using Text Messaging in Long-Term Arthroplasty Follow-Up: A Pilot Study.
AB  - BACKGROUND: Patient-reported outcome measures (PROMs) and mobile technology have
      the potential to change the way patients are monitored following joint
      replacement surgery. OBJECTIVE: The aim of this study was to determine the
      feasibility of text messaging to record PROMs in long-term follow-up of hip and
      knee arthroplasty. Our participants were 17 patients 2-years-plus post hip or
      knee arthroplasty attending clinic with a mobile telephone number on record.
      METHODS: A simple PROM (Oswestry Very Short Form) was texted to the patient.
      Responses were compared to clinical, radiographic, and existing PROM findings.
      Patients were interviewed to discover their opinions on this use of texting.
      RESULTS: A total of 11 patients engaged with the text messaging. Reasons for not
      engaging included wrong numbers, physical barriers, and lack of understanding. A
      total of 8 patients attending clinic allowed comparison of text messaging with
      clinical findings. The average age was 70 years. A total of 4 patient text
      messaging responses matched clinical and radiographic findings; 3 also matched
      PROM scores collected in clinic. The 3 patients with mixed responses had abnormal
      clinical, radiographic, or PROM findings. One patient's text responses conflicted
      with clinical outcome. Analysis of patients' views showed a generally positive
      opinion: patients were happy to communicate with surgeons by text. Practical
      problems, PROM limitations, and trustworthiness of texting were highlighted.
      CONCLUSIONS: Engaging with changing technology creates challenges for patients
      and health care professionals. Despite this, our results suggest text messaging
      is a promising way to communicate with arthroplasty patients. Earlier integration
      of text communication in the patient pathway may be important and needs further
      research.

PMID- 28512081
TI  - Effects of eHealth Literacy on General Practitioner Consultations: A Mediation
      Analysis.
AB  - BACKGROUND: Most evidence (not all) points in the direction that individuals with
      a higher level of health literacy will less frequently utilize the health care
      system than individuals with lower levels of health literacy. The underlying
      reasons of this effect are largely unclear, though people's ability to seek
      health information independently at the time of wide availability of such
      information on the Internet has been cited in this context. OBJECTIVE: We propose
      and test two potential mediators of the negative effect of eHealth literacy on
      health care utilization: (1) health information seeking and (2) gain in
      empowerment by information seeking. METHODS: Data were collected in New Zealand,
      the United Kingdom, and the United States using a Web-based survey administered
      by a company specialized on providing online panels. Combined, the three samples
      resulted in a total of 996 baby boomers born between 1946 and 1965 who had used
      the Internet to search for and share health information in the previous 6 months.
      Measured variables include eHealth literacy, Internet health information seeking,
      the self-perceived gain in empowerment by that information, and the number of
      consultations with one's general practitioner (GP). Path analysis was employed
      for data analysis. RESULTS: We found a bundle of indirect effect paths showing a
      positive relationship between health literacy and health care utilization: via
      health information seeking (Path 1), via gain in empowerment (Path 2), and via
      both (Path 3). In addition to the emergence of these indirect effects, the direct
      effect of health literacy on health care utilization disappeared. CONCLUSIONS:
      The indirect paths from health literacy via information seeking and empowerment
      to GP consultations can be interpreted as a dynamic process and an expression of
      the ability to find, process, and understand relevant information when that is
      necessary.

PMID- 28512082
TI  - Medical Student Evaluation With a Serious Game Compared to Multiple Choice
      Questions Assessment.
AB  - BACKGROUND: The gold standard for evaluating medical students' knowledge is by
      multiple choice question (MCQs) tests: an objective and effective means of
      restituting book-based knowledge. However, concerns have been raised regarding
      their effectiveness to evaluate global medical skills. Furthermore, MCQs of
      unequal difficulty can generate frustration and may also lead to a sizable
      proportion of close results with low score variability. Serious games (SG) have
      recently been introduced to better evaluate students' medical skills. OBJECTIVES:
      The study aimed to compare MCQs with SG for medical student evaluation. METHODS:
      We designed a cross-over randomized study including volunteer medical students
      from two medical schools in Paris (France) from January to September 2016. The
      students were randomized into two groups and evaluated either by the SG first and
      then the MCQs, or vice-versa, for a cardiology clinical case. The primary
      endpoint was score variability evaluated by variance comparison. Secondary
      endpoints were differences in and correlation between the MCQ and SG results, and
      student satisfaction. RESULTS: A total of 68 medical students were included. The
      score variability was significantly higher in the SG group (sigma2 =265.4) than
      the MCQs group (sigma2=140.2; P=.009). The mean score was significantly lower for
      the SG than the MCQs at 66.1 (SD 16.3) and 75.7 (SD 11.8) points out of 100,
      respectively (P<.001). No correlation was found between the two test results
      (R2=0.04, P=.58). The self-reported satisfaction was significantly higher for SG
      (P<.001). CONCLUSIONS: Our study suggests that SGs are more effective in terms of
      score variability than MCQs. In addition, they are associated with a higher
      student satisfaction rate. SGs could represent a new evaluation modality for
      medical students.

PMID- 28512084
TI  - GPs use pen and paper after IT systems are shut down as precaution.

PMID- 28512083
TI  - The impact of not having enough staff is exhausting and detrimental to patient
      care.

PMID- 28512087
TI  - Cannabis as medicine.

PMID- 28512086
TI  - Two Loci Contribute Epistastically to Heterospecific Pollen Rejection, a
      Postmating Isolating Barrier Between Species.
AB  - Recognition and rejection of heterospecific male gametes occurs in a broad range
      of taxa, although the complexity of mechanisms underlying these components of
      postmating cryptic female choice is poorly understood. In plants, the arena for
      postmating interactions is the female reproductive tract (pistil), within which
      heterospecific pollen tube growth can be arrested via active molecular
      recognition and rejection. Unilateral incompatibility (UI) is one such postmating
      barrier in which pollen arrest occurs in only one direction of an interspecific
      cross. We investigated the genetic basis of pistil-side UI between Solanum
      species, with the specific goal of understanding the role and magnitude of
      epistasis between UI QTL. Using heterospecific introgression lines (ILs) between
      Solanum pennellii and S. lycopersicum, we assessed the individual and pairwise
      effects of three chromosomal regions (ui1.1, ui3.1, and ui12.1) previously
      associated with interspecific UI among Solanum species. Specifically, we
      generated double introgression ('pyramided') genotypes that combined ui12.1 with
      each of ui1.1 and ui3.1, and assessed the strength of UI pollen rejection in the
      pyramided lines, compared to single introgression genotypes. We found that none
      of the three QTL individually showed UI rejection phenotypes, but lines combining
      ui3.1 and ui12.1 showed significant pistil-side pollen rejection. Furthermore,
      double ILs (DILs) that combined different chromosomal regions overlapping ui3.1
      differed significantly in their rate of UI, consistent with at least two genetic
      factors on chromosome three contributing quantitatively to interspecific pollen
      rejection. Together, our data indicate that loci on both chromosomes 3 and 12 are
      jointly required for the expression of UI between S. pennellii and S.
      lycopersicum, suggesting that coordinated molecular interactions among a
      relatively few loci underlie the expression of this postmating prezygotic
      barrier. In addition, in conjunction with previous data, at least one of these
      loci appears to also contribute to conspecific self-incompatibility (SI),
      consistent with a partially shared genetic basis between inter- and intraspecific
      mechanisms of postmating prezygotic female choice.

PMID- 28512088
TI  - TRPV4 in the battle of the sexes.
AB  - New JGP paper explains sexual dimorphism and tissue-specific activity of TRPV4.

PMID- 28512085
TI  - Self reported outcomes and adverse events after medical abortion through online
      telemedicine: population based study in the Republic of Ireland and Northern
      Ireland.
AB  - Objectives To assess self reported outcomes and adverse events after self sourced
      medical abortion through online telemedicine.Design Population based
      study.Setting Republic of Ireland and Northern Ireland, where abortion is
      unavailable through the formal healthcare system except in a few restricted
      circumstances.Population 1000 women who underwent self sourced medical abortion
      through Women on Web (WoW), an online telemedicine service, between 1 January
      2010 and 31 December 2012.Main outcome measures Successful medical abortion: the
      proportion of women who reported ending their pregnancy without surgical
      intervention. Rates of adverse events: the proportion who reported treatment for
      adverse events, including receipt of antibiotics and blood transfusion, and
      deaths reported by family members, friends, or the authorities. Care seeking for
      symptoms of potential complications: the frequency with which women reported
      experiencing symptoms of a potentially serious complication and the proportion
      who reported seeking medical attention as advised.Results In 2010-12, abortion
      medications (mifepristone and misoprostol) were sent to 1636 women and follow-up
      information was obtained for 1158 (71%). Among these, 1023 women confirmed use of
      the medications, and follow-up information was available for 1000. At the time
      women requested help from WoW, 781 (78%) were <7 weeks pregnant and 219 (22%)
      were 7-9 weeks pregnant. Overall, 94.7% (95% confidence interval 93.1% to 96.0%)
      reported successfully ending their pregnancy without surgical intervention. Seven
      women (0.7%, 0.3% to 1.5%) reported receiving a blood transfusion, and 26 (2.6%,
      1.7% to 3.8%) reported receiving antibiotics (route of administration (IV or
      oral) could not be determined). No deaths resulting from the intervention were
      reported by family, friends, the authorities, or the media. Ninety three women
      (9.3%, 7.6% to 11.3%) reported experiencing any symptom for which they were
      advised to seek medical advice, and, of these, 87 (95%, 87.8% to 98.2%) sought
      attention. None of the five women who did not seek medical attention reported
      experiencing an adverse outcome.Conclusions Self sourced medical abortion using
      online telemedicine can be highly effective, and outcomes compare favourably with
      in clinic protocols. Reported rates of adverse events are low. Women are able to
      self identify the symptoms of potentially serious complications, and most report
      seeking medical attention when advised. Results have important implications for
      women worldwide living in areas where access to abortion is restricted.

PMID- 28512089
TI  - Physician age and outcomes in elderly patients in hospital in the US:
      observational study.
AB  - Objectives To investigate whether outcomes of patients who were admitted to
      hospital differ between those treated by younger and older physicians.Design
      Observational study.Setting US acute care hospitals.Participants 20% random
      sample of Medicare fee-for-service beneficiaries aged >=65 admitted to hospital
      with a medical condition in 2011-14 and treated by hospitalist physicians to whom
      they were assigned based on scheduled work shifts. To assess the generalizability
      of findings, analyses also included patients treated by general internists
      including both hospitalists and non-hospitalists.Main outcome measures 30 day
      mortality and readmissions and costs of care. Results 736 537 admissions managed
      by 18 854 hospitalist physicians (median age 41) were included. Patients'
      characteristics were similar across physician ages. After adjustment for
      characteristics of patients and physicians and hospital fixed effects
      (effectively comparing physicians within the same hospital), patients' adjusted
      30 day mortality rates were 10.8% for physicians aged <40 (95% confidence
      interval 10.7% to 10.9%), 11.1% for physicians aged 40-49 (11.0% to 11.3%), 11.3%
      for physicians aged 50-59 (11.1% to 11.5%), and 12.1% for physicians aged >=60
      (11.6% to 12.5%). Among physicians with a high volume of patients, however, there
      was no association between physician age and patient mortality. Readmissions did
      not vary with physician age, while costs of care were slightly higher among older
      physicians. Similar patterns were observed among general internists and in
      several sensitivity analyses.Conclusions Within the same hospital, patients
      treated by older physicians had higher mortality than patients cared for by
      younger physicians, except those physicians treating high volumes of patients.

PMID- 28512090
TI  - The Vibrio cholerae VexGH RND Efflux System Maintains Cellular Homeostasis by
      Effluxing Vibriobactin.
AB  - Resistance-nodulation-division (RND) superfamily efflux systems have been widely
      studied for their role in antibiotic resistance, but their native biological
      functions remain poorly understood. We previously showed that loss of RND
      mediated efflux in Vibrio cholerae resulted in activation of the Cpx two
      component regulatory system, which mediates adaptation to stress resulting from
      misfolded membrane proteins. Here, we investigated the mechanism linking RND
      mediated efflux to the Cpx response. We performed transposon mutagenesis
      screening of RND-deficient V. cholerae to identify Cpx suppressors. Suppressor
      mutations mapped to genes involved in the biosynthesis of the catechol
      siderophore vibriobactin. We subsequently demonstrated that vibriobactin
      secretion is impaired in mutants lacking the VexGH RND efflux system and that
      impaired vibriobactin secretion is responsible for Cpx system activation,
      suggesting that VexGH secretes vibriobactin. This conclusion was bolstered by
      results showing that vexGH expression is induced by iron limitation and that vexH
      deficient cells exhibit reduced fitness during growth under iron-limiting
      conditions. Our results support a model where VexGH contributes to cellular
      homeostasis by effluxing vibriobactin. In the absence of vexGH, retained
      vibriobactin appears to chelate iron from iron-rich components of the respiratory
      chain, with the deferrated proteins functioning to activate the Cpx response. Our
      collective results demonstrate that a native function of the V. cholerae VexGH
      RND efflux system is in vibriobactin secretion and that vibriobactin efflux is
      critical for maintenance of cellular homeostasis.IMPORTANCE RND efflux systems
      are ubiquitous Gram-negative transporters that play critical roles in
      antimicrobial resistance. In addition to antimicrobial resistance, RND
      transporters also affect the expression of diverse phenotypes, including
      virulence, cell metabolism, and stress responses. The latter observations suggest
      that RND transporters fulfill unknown physiological functions in the cell
      independently of their role in antimicrobial resistance. Vibrio cholerae is
      representative of many Gram-negative bacteria in encoding multiple RND
      transporters that are redundant in antimicrobial resistance and affect multiple
      phenotypes. Here we describe a novel function of the V. cholerae VexGH RND
      transporter in vibriobactin secretion. We show that vibriobactin production in
      VexGH-deficient cells impacts cell homeostasis, leading to activation of the Cpx
      stress response and reduced fitness under iron-limiting conditions. Our results
      highlight a native physiological function of an RND transporter and provide
      insight into the selective forces that maintain what was thought to be a
      redundant multidrug transporter.

PMID- 28512092
TI  - Quantitative Kinetic Analyses of Shutting Off a Two-Component System.
AB  - Cells rely on accurate control of signaling systems to adapt to environmental
      perturbations. System deactivation upon stimulus removal is as important as
      activation of signaling pathways. The two-component system (TCS) is one of the
      major bacterial signaling schemes. In many TCSs, phosphatase activity of the
      histidine kinase (HK) is believed to play an essential role in shutting off the
      pathway and resetting the system to the prestimulus state. Two basic challenges
      are to understand the dynamic behavior of system deactivation and to
      quantitatively evaluate the role of phosphatase activity under natural cellular
      conditions. Here we report a kinetic analysis of the response to shutting off the
      archetype Escherichia coli PhoR-PhoB TCS pathway using both transcription
      reporter assays and in vivo phosphorylation analyses. Upon removal of the
      stimulus, the pathway is shut off by rapid dephosphorylation of the PhoB response
      regulator (RR) while PhoB-regulated gene products gradually reset to prestimulus
      levels through growth dilution. We developed an approach combining
      experimentation and modeling to assess in vivo kinetic parameters of the
      phosphatase activity with kinetic data from multiple phosphatase-diminished
      mutants. This enabled an estimation of the PhoR phosphatase activity in vivo,
      which is much stronger than the phosphatase activity of PhoR cytoplasmic domains
      analyzed in vitro We quantitatively modeled how strong the phosphatase activity
      needs to be to suppress nonspecific phosphorylation in TCSs and discovered that
      strong phosphatase activity of PhoR is required for cross-phosphorylation
      suppression.IMPORTANCE Activation of TCSs has been extensively studied; however,
      the kinetics of shutting off TCS pathways is not well characterized. We present
      comprehensive analyses of the shutoff response for the PhoR-PhoB system that
      reveal the impact of phosphatase activity on shutoff kinetics. This allows
      development of a quantitative framework not only to characterize the phosphatase
      activity in the natural cellular environment but also to understand the
      requirement for specific strengths of phosphatase activity to suppress
      nonspecific phosphorylation. Our model suggests that the ratio of the phosphatase
      rate to the nonspecific phosphorylation rate correlates with TCS expression
      levels and the ratio of the RR to HK, which may contribute to the great diversity
      of enzyme levels and activities observed in different TCSs.

PMID- 28512091
TI  - Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C
      Virus Glycoprotein E2.
AB  - The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing
      antibodies and is therefore highly relevant for vaccine design. Its structure
      features a central immunoglobulin (Ig)-like beta-sandwich that contributes to the
      binding site for the cellular receptor CD81. We show that a synthetic peptide
      corresponding to a beta-strand of this Ig-like domain forms an alpha-helix in
      complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of
      hydrophobic residues and a secondary structure change in the composite CD81
      binding site. A detailed interaction analysis of DAO5 and cross-competing
      neutralizing antibodies with soluble E2 revealed that the Ig-like domain is
      trapped by different antibodies in at least two distinct conformations. DAO5
      specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and
      infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5
      captured HCVpp can be blocked by a cross-competing neutralizing antibody,
      indicating that a single virus particle simultaneously displays E2 molecules in
      more than one conformation on its surface. Such conformational plasticity of the
      HCV E2 receptor binding site has important implications for immunogen
      design.IMPORTANCE Recent advances in the treatment of hepatitis C virus (HCV)
      infection with direct-acting antiviral drugs have enabled the control of this
      major human pathogen. However, due to their high costs and limited accessibility
      in combination with the lack of awareness of the mostly asymptomatic infection,
      there is an unchanged urgent need for an effective vaccine. The viral
      glycoprotein E2 contains regions that are crucial for virus entry into the host
      cell, and antibodies that bind to these regions can neutralize infection. One of
      the major targets of neutralizing antibodies is the central immunoglobulin (Ig)
      like domain within E2. We show here that this Ig-like domain is conformationally
      flexible at the surface of infectious HCV particles and pseudoparticles. Our
      study provides novel insights into the interactions of HCV E2 with the humoral
      immune system that should aid future vaccine development.

PMID- 28512094
TI  - Intrinsic Toxin-Derived Peptides Destabilize and Inactivate Clostridium difficile
      TcdB.
AB  - Clostridium difficile infection (CDI) is a major cause of hospital-associated,
      antibiotic-induced diarrhea, which is largely mediated by the production of two
      large multidomain clostridial toxins, TcdA and TcdB. Both toxins coordinate the
      action of specific domains to bind receptors, enter cells, and deliver a
      catalytic fragment into the cytosol. This results in GTPase inactivation, actin
      disassembly, and cytotoxicity. TcdB in particular has been shown to encode a
      region covering amino acids 1753 to 1851 that affects epitope exposure and
      cytotoxicity. Surprisingly, studies here show that several peptides derived from
      this region, which share the consensus sequence 1769NVFKGNTISDK1779, protect
      cells from the action of TcdB. One peptide, PepB2, forms multiple interactions
      with the carboxy-terminal region of TcdB, destabilizes TcdB structure, and
      disrupts cell binding. We further show that these effects require PepB2 to form a
      higher-order polymeric complex, a process that requires the central GN amino acid
      pair. These data suggest that TcdB1769-1779 interacts with repeat sequences in
      the proximal carboxy-terminal domain of TcdB (i.e., the CROP domain) to alter the
      conformation of TcdB. Furthermore, these studies provide insights into TcdB
      structure and functions that can be exploited to inactivate this critical
      virulence factor and ameliorate the course of CDI.IMPORTANCEClostridium difficile
      is a leading cause of hospital-associated illness that is often associated with
      antibiotic treatment. To cause disease, C. difficile secretes toxins, including
      TcdB, which is a multidomain intracellular bacterial toxin that undergoes
      conformational changes during cellular intoxication. This study describes the
      development of peptide-based inhibitors that target a region of TcdB thought to
      be critical for structural integrity of the toxin. The results show that peptides
      derived from a structurally important region of TcdB can be used to destabilize
      the toxin and prevent cellular intoxication. Importantly, this work provides a
      novel means of toxin inhibition that could in the future develop into a C.
      difficile treatment.

PMID- 28512096
TI  - Erratum for Briese et al., "Virome Capture Sequencing Enables Sensitive Viral
      Diagnosis and Comprehensive Virome Analysis".

PMID- 28512093
TI  - Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing
      Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal
      Group 307.
AB  - Klebsiella pneumoniae is a major human pathogen responsible for high morbidity
      and mortality rates. The emergence and spread of strains resistant to multiple
      antimicrobial agents and documented large nosocomial outbreaks are especially
      concerning. To develop new therapeutic strategies for K. pneumoniae, it is
      imperative to understand the population genomic structure of strains causing
      human infections. To address this knowledge gap, we sequenced the genomes of
      1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured
      from patients in the 2,000-bed Houston Methodist Hospital system between
      September 2011 and May 2015, representing a comprehensive, population-based
      strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused
      more infections than those of well-studied epidemic CG258. Strains varied
      markedly in gene content and had an extensive array of small and very large
      plasmids, often containing antimicrobial resistance genes. Some patients with
      multiple strains cultured over time were infected with genetically distinct
      clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase
      1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam
      antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse
      strains showed that the global transcriptome of each strain was unique and highly
      variable. Experimental mouse infection provided new information about
      immunological parameters of host-pathogen interaction. We exploited the large
      data set to develop whole-genome sequence-based classifiers that accurately
      predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We
      conclude that analysis of large, comprehensive, population-based strain samples
      can assist understanding of the molecular diversity of these organisms and
      contribute to enhanced translational research.IMPORTANCEKlebsiella pneumoniae
      causes human infections that are increasingly difficult to treat because many
      strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms
      have caused outbreaks in health care settings worldwide. Using a comprehensive
      population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K.
      pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused
      the plurality of ESBL-producing K. pneumoniae infections in our patients. We
      discovered that CG307 strains have been abundant in Houston for many years. As
      assessed by experimental mouse infection, CG307 strains were as virulent as
      pandemic CG258 strains. Our results may portend the emergence of an especially
      successful clonal group of antibiotic-resistant K. pneumoniae.

PMID- 28512095
TI  - Structure-Based Mutations in the Herpes Simplex Virus 1 Glycoprotein B Ectodomain
      Arm Impart a Slow-Entry Phenotype.
AB  - Glycoprotein B (gB) is the conserved herpesvirus fusion protein, and it is
      required for the entry of herpesviruses. The structure of the postfusion
      conformation of gB has been solved for several herpesviruses; however, the gB
      prefusion crystal structure and the details of how the protein refolds from a
      prefusion to a postfusion form to mediate fusion have not been determined. Using
      structure-based mutagenesis, we previously reported that three mutations (I671A,
      H681A, and F683A) in the C-terminal arm of the gB ectodomain greatly reduced cell
      cell fusion. This fusion deficit could be rescued by the addition of a
      hyperfusogenic mutation, suggesting that the gB triple mutant was not misfolded.
      Using a bacterial artificial chromosome (BAC), we constructed two independent
      herpes simplex virus 1 mutant strains (gB 3A) carrying the three arm mutations.
      The gB 3A viruses have 200-fold smaller plaques than the wild-type virus and
      demonstrate remarkably delayed entry into cells. Single-step and multistep growth
      curves show that gB 3A viruses have delayed replication kinetics. Interestingly,
      incubation at 40 degrees C promoted the entry of the gB 3A viruses. We propose
      that the gB 3A viruses' entry deficit is due to a loss of interactions between
      residues in the gB C-terminal arm and the coiled-coil core of gB. The results
      suggest that the triple alanine mutation may destabilize the postfusion gB
      conformation and/or stabilize the prefusion gB conformation and that exposure to
      elevated temperatures can overcome the defect in gB 3A viruses.IMPORTANCE Because
      of its complexity, the mechanism of herpesvirus entry into cells is not well
      understood. Our study investigated one of the most important unanswered questions
      about herpesvirus entry; i.e., how does the herpesvirus fusion protein gB mediate
      membrane fusion? gB is an essential protein that is conserved in all
      herpesviruses and is thought to undergo a conformational change to provide the
      energy to fuse the viral and cellular membranes. Using our understanding of the
      structure of gB, we designed mutations in the gB "arm" region that we predicted
      would impede gB function. We introduced these mutations into herpes simplex virus
      1 by using a bacterial artificial chromosome, and the mutant virus exhibited a
      drastically delayed rate of entry. This entry defect was rescued by incubation at
      elevated temperatures, supporting a hypothesis that the engineered mutations
      altered the energetics of gB refolding. This study supports our hypothesis that
      an interaction between the gB arm and the core of gB is critical for gB refolding
      and the execution of membrane fusion, thus providing key details about the
      function of gB in herpesvirus-mediated fusion and subsequent virus entry.

PMID- 28512098
TI  - A rare case of thrombotic microangiopathy triggered by acute pancreatitis.
AB  - Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely
      described. Without prompt intervention, TMA can be, and often is, lethal, so
      prompt recognition is important. Here, we present a case of a 61-year-old woman
      with a history of alcohol misuse who presented with epigastric pain, nausea and
      vomiting after binge drinking. Elevated serum lipase and imaging were suggestive
      of acute-on-chronic pancreatitis. Although the patient's symptoms of acute
      pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury
      worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for
      TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed
      10 TPE sessions that improved her anaemia and serum creatinine and resolved the
      thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55%
      activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a
      confident diagnosis of TMA caused by acute pancreatitis was made. There was no
      evidence of relapse 2 years later.

PMID- 28512097
TI  - Glutathionylation of Yersinia pestis LcrV and Its Effects on Plague Pathogenesis.
AB  - Glutathionylation, the formation of reversible mixed disulfides between
      glutathione and protein cysteine residues, is a posttranslational modification
      previously observed for intracellular proteins of bacteria. Here we show that
      Yersinia pestis LcrV, a secreted protein capping the type III secretion machine,
      is glutathionylated at Cys273 and that this modification promotes association
      with host ribosomal protein S3 (RPS3), moderates Y. pestis type III effector
      transport and killing of macrophages, and enhances bubonic plague pathogenesis in
      mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to
      reveal glutathionylation, a modification that is abolished by the codon
      substitution Cys273Ala in lcrV Moreover, the lcrVC273A mutation enhanced the
      survival of animals in models of bubonic plague. Investigating the molecular
      mechanism responsible for these virulence attributes, we identified macrophage
      RPS3 as a ligand of LcrV, an association that is perturbed by the Cys273Ala
      substitution. Furthermore, macrophages infected by the lcrVC273A variant
      displayed accelerated apoptotic death and diminished proinflammatory cytokine
      release. Deletion of gshB, which encodes glutathione synthetase of Y. pestis,
      resulted in undetectable levels of intracellular glutathione, and we used a Y.
      pestis DeltagshB mutant to characterize the biochemical pathway of LcrV
      glutathionylation, establishing that LcrV is modified after its transport to the
      type III needle via disulfide bond formation with extracellular oxidized
      glutathione.IMPORTANCEYersinia pestis, the causative agent of plague, has killed
      large segments of the human population; however, the molecular bases for the
      extraordinary virulence attributes of this pathogen are not well understood. We
      show here that LcrV, the cap protein of bacterial type III secretion needles, is
      modified by host glutathione and that this modification contributes to the high
      virulence of Y. pestis in mouse and rat models for bubonic plague. These data
      suggest that Y. pestis exploits glutathione in host tissues to activate a
      virulence strategy, thereby accelerating plague pathogenesis.

PMID- 28512099
TI  - Mitral valve vegetation diagnosed with oesophageal ultrasound with bronchoscope
      (EUS-B).
AB  - Oesophageal ultrasound with bronchoscope (EUS-B) is designed to evaluate
      mediastinal structures. We describe a case of a 78-year-old woman who presented
      with altered mental status for 2 weeks. CT head revealed a subacute infarct in
      the right middle cerebral artery distribution. She was also found to have a lung
      mass on chest imaging. EUS-B-guided fine needle aspiration demonstrated the
      presence of adenocarcinoma in station 7 lymph node and in the mass.
      Immunohistochemistry confirmed it to be a lung primary as the Thyroid
      Transcription Factor-1 (TTF-1) was strongly positive. During the procedure, the
      cardiac valves were evaluated, and a mitral valve vegetation was noted. Formal
      echocardiography confirmed the presence of the vegetation. During hospital stay,
      the patient developed fever. Her blood cultures grew oxacillin-resistant
      Staphylococcus aureus. She was subsequently treated for infective endocarditis.
      We suggest that the use of EUS-B to routinely scan adjacent structures during a
      procedure may help obtain additional clinical information that may be critical to
      patient management.

PMID- 28512100
TI  - Anaemia and respiratory failure in a child: can it be idiopathic pulmonary
      haemosiderosis?
AB  - We present an 8-year-old male child admitted with cough and high-grade fever for
      7 days and respiratory difficulty for 2 days. There was a history of blood
      transfusion at 2 years of age during a respiratory illness. The child was
      anaemic, tachycardic, tachypnoeic and hypoxic at presentation. Chest examination
      revealed equal air entry with fine crackles bilaterally. Blood reports were
      suggestive of anaemia (haemoglobin 6.5 g/dL), leucocytosis and high C reactive
      protein levels. Chest radiograph revealed bilateral air space opacities involving
      diffuse lung fields, right more than left. Relevant microbiological workup was
      negative. Based on the clinical scenario and investigations, a provisional
      diagnosis of pulmonary haemosiderosis was kept. The patient was started on
      intravenous pulse methylprednisolone. Fibre-optic bronchoscopy was done following
      recovery from the acute event. Bronchoalveolar lavage demonstrated a significant
      number of haemosiderin-laden macrophages confirming pulmonary haemosiderosis.

PMID- 28512101
TI  - Novel use of combination of electromyography and ultrasound to guide quadratus
      lumborum block after open appendicectomy.
AB  - The quadratus lumborum (QL) block facilitates the administration of anaesthesia
      to the anterior abdominal wall. The use of ultrasound (US) improves the accuracy
      of the QL block and reduces the risk of adverse events. Electromyography (EMG) in
      combination with US for muscle plane blocks has not been described previously. We
      postulated that the addition of EMG-guided needle positioning might assist the
      execution of this block. This case report describes the first use of combined
      needle EMG and US to carry out a QL block performed for postoperative analgesia
      following an open appendicectomy.

PMID- 28512102
TI  - Uncommon presentation of adult-form scimitar syndrome associated with single left
      pulmonary vein in a pregnant woman.
AB  - Scimitar syndrome is the constellation of malformations including an abnormal
      venous drainage of the right lung into the inferior vena cava, associated with
      the right lung and systemic supply to the right lung. The anomalous vein looks
      like the curved, Turkish sword (scimitar), hence the name.The adult form of
      scimitar syndrome is rare, and it is usually an incidental diagnosis based on the
      characteristic finding on radiological imaging since the patients are usually
      asymptomatic or with minimal symptoms.Our patient presented with a rare
      presentation of scimitar syndrome, which is tachyarrhythmia (sinus tachycardia,
      with episodes of supraventricular tachycardia). The diagnosis of scimitar
      syndrome was made based on the typical radiological finding of the anomalous
      venous drainage on CT angiography. Our patient does not have the full spectrum of
      the scimitar syndrome; therefore, she did not suffer from the usual complication
      (pulmonary hypertension). She was treated with ablation without surgical
      intervention.

PMID- 28512103
TI  - Pericardial incidentaloma: benign pericardial cyst.

PMID- 28512104
TI  - Mitral Stenosis.

PMID- 28512106
TI  - David Oliver: The NHS's understaffing is its Achilles' heel.

PMID- 28512105
TI  - Double hit lymphoma presenting as haemophagocytic lymphohistiocytosis.

PMID- 28512107
TI  - Divergent Requirements for EZH1 in Heart Development Versus Regeneration.
AB  - RATIONALE: Polycomb repressive complex 2 is a major epigenetic repressor that
      deposits methylation on histone H3 on lysine 27 (H3K27me) and controls
      differentiation and function of many cells, including cardiac myocytes. EZH1 and
      EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The
      relative roles of EZH1 and EZH2 in heart development and regeneration are
      unknown. OBJECTIVE: We compared the roles of EZH1 versus EZH2 in heart
      development and neonatal heart regeneration. METHODS AND RESULTS: Heart
      development was normal in Ezh1-/- (Ezh1 knockout) and Ezh2f/f::cTNT-Cre (Ezh2
      knockout) embryos. Ablation of both genes in Ezh1-/-::Ezh2f/f::cTNT-Cre embryos
      caused lethal heart malformations, including hypertrabeculation, compact
      myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome
      profiling showed that derepressed genes were upregulated in a manner consistent
      with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2
      was dispensable. This finding was further supported by rescue experiments:
      cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal
      heart regeneration in Ezh1 knockout. In myocardial infarction performed outside
      of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart
      function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1
      occupied and activated genes related to cardiac growth. CONCLUSIONS: Our work
      unravels divergent mechanisms of EZH1 in heart development and regeneration,
      which will empower efforts to overcome epigenetic barriers to heart regeneration.

PMID- 28512110
TI  - In patients with intracerebral haemorrhage and concomitant atrial fibrillation,
      optimal timing of reinitiating anticoagulants may be 7-8 weeks after ICH.

PMID- 28512109
TI  - Resumption of anticoagulation after major bleeding decreases the risk of stroke
      in patients with atrial fibrillation.

PMID- 28512108
TI  - Clinical Relevance and Role of Neuronal AT1 Receptors in ADAM17-Mediated ACE2
      Shedding in Neurogenic Hypertension.
AB  - RATIONALE: Neurogenic hypertension is characterized by an increase in sympathetic
      activity and often resistance to drug treatments. We previously reported that it
      is also associated with a reduction of angiotensin-converting enzyme type 2
      (ACE2) and an increase in a disintegrin and metalloprotease 17 (ADAM17) activity
      in experimental hypertension. In addition, while multiple cells within the
      central nervous system have been involved in the development of neurogenic
      hypertension, the contribution of ADAM17 has not been investigated. OBJECTIVE: To
      assess the clinical relevance of this ADAM17-mediated ACE2 shedding in
      hypertensive patients and further identify the cell types and signaling pathways
      involved in this process. METHODS AND RESULTS: Using a mass spectrometry-based
      assay, we identified ACE2 as the main enzyme converting angiotensin II into
      angiotensin-(1-7) in human cerebrospinal fluid. We also observed an increase in
      ACE2 activity in the cerebrospinal fluid of hypertensive patients, which was
      correlated with systolic blood pressure. Moreover, the increased level of tumor
      necrosis factor-alpha in those cerebrospinal fluid samples confirmed that ADAM17
      was upregulated in the brain of hypertensive patients. To further assess the
      interaction between brain renin-angiotensin system and ADAM17, we generated mice
      lacking angiotensin II type 1 receptors specifically on neurons. Our data reveal
      that despite expression on astrocytes and other cells types in the brain, ADAM17
      upregulation during deoxycorticosterone acetate-salt hypertension occurs
      selectively on neurons, and neuronal angiotensin II type 1 receptors are
      indispensable to this process. Mechanistically, reactive oxygen species and
      extracellular signal-regulated kinase were found to mediate ADAM17 activation.
      CONCLUSIONS: Our data demonstrate that angiotensin II type 1 receptors promote
      ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a
      loss in compensatory activity during neurogenic hypertension.

PMID- 28512111
TI  - An Initial Evaluation of the Impact of Pokemon GO on Physical Activity.
AB  - BACKGROUND: Pokemon GO is a location-based augmented reality game. Using GPS and
      the camera on a smartphone, the game requires players to travel in real world to
      capture animated creatures, called Pokemon. We examined the impact of Pokemon GO
      on physical activity (PA). METHODS AND RESULTS: A pre-post observational study of
      167 Pokemon GO players who were self-enrolled through recruitment flyers or
      online social media was performed. Participants were instructed to provide
      screenshots of their step counts recorded by the iPhone Health app between June
      15 and July 31, 2016, which was 3 weeks before and 3 weeks after the Pokemon GO
      release date. Of 167 participants, the median age was 25 years (interquartile
      range, 21-29 years). The daily average steps of participants at baseline was 5678
      (SD, 2833; median, 5718 [interquartile range, 3675-7279]). After initiation of
      Pokemon GO, daily activity rose to 7654 steps (SD, 3616; median, 7232
      [interquartile range, 5041-9744], pre-post change: 1976; 95% CI, 1494-2458, or a
      34.8% relative increase [P<0.001]). On average, 10 000 "XP" points (a measure of
      game progression) was associated with 2134 additional steps per day (95% CI, 1673
      2595), suggesting a potential dose-response relationship. The number of
      participants achieving a goal of 10 000+ steps per day increased from 15.3%
      before to 27.5% after (odds ratio, 2.06; 95% CI, 1.70-2.50). Increased PA was
      also observed in subgroups, with the largest increases seen in participants who
      spent more time playing Pokemon GO, those who were overweight/obese, or those
      with a lower baseline PA level. CONCLUSIONS: Pokemon GO participation was
      associated with a significant increase in PA among young adults. Incorporating PA
      into gameplay may provide an alternative way to promote PA in persons who are
      attracted to the game. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02888314.

PMID- 28512113
TI  - How Symptomatic Should a Hypertrophic Obstructive Cardiomyopathy Patient Be to
      Consider Alcohol Septal Ablation?

PMID- 28512112
TI  - Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With
      Hypertrophic Obstructive Cardiomyopathy: A Long-Term Follow-Up Study Based on the
      Euro-Alcohol Septal Ablation Registry.
AB  - BACKGROUND: The long-term efficacy and safety of alcohol septal ablation (ASA) in
      patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been
      demonstrated. The aim of this study was to evaluate the long-term outcomes of
      mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated
      with ASA. METHODS AND RESULTS: We retrospectively evaluated consecutive patients
      enrolled in the Euro-ASA registry (1427 patients) and identified 161 patients
      (53+/-13 years; 27% women) who were mildly symptomatic (New York Heart
      Association [NYHA] class II) pre-ASA. The median (interquartile range) follow-up
      was 4.8 (1.7-8.5) years. The clinical outcome was assessed and compared with the
      age- and sex-matched general population. The 30-day mortality after ASA was 0.6%
      and the annual all-cause mortality rate was 1.7%, which was similar to the age-
      and sex-matched general population (P=0.62). A total of 141 (88%) patients had
      resting left ventricular outflow tract gradient at the last clinical checkup <=30
      mm Hg. Obstruction was reduced from 63+/-32 to 15+/-19 mm Hg (P<0.01), and the
      mean NYHA class decreased from 2.0+/-0 to 1.3+/-0.1 (P<0.01); 69%, 29%, and 2% of
      patients were in NYHA class I, II, and III at the last clinical checkup,
      respectively. CONCLUSIONS: Mildly symptomatic hypertrophic obstructive
      cardiomyopathy patients treated with ASA had sustained symptomatic and
      hemodynamic relief with a low risk of developing severe heart failure. Their
      survival is comparable to the general population.

PMID- 28512115
TI  - Endogenous Hydrogen Sulfide Enhances Carotid Sinus Baroreceptor Sensitivity by
      Activating the Transient Receptor Potential Cation Channel Subfamily V Member 1
      (TRPV1) Channel.
AB  - BACKGROUND: We aimed to investigate the regulatory effects of hydrogen sulfide
      (H2S) on carotid sinus baroreceptor sensitivity and its mechanisms. METHODS AND
      RESULTS: Male Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) were
      used in the experiment and were given an H2S donor or a cystathionine-beta
      synthase inhibitor, hydroxylamine, for 8 weeks. Systolic blood pressure and the
      cystathionine-beta-synthase/H2S pathway in carotid sinus were detected. Carotid
      sinus baroreceptor sensitivity and the functional curve of the carotid
      baroreceptor were analyzed using the isolated carotid sinus perfusion technique.
      Effects of H2S on transient receptor potential cation channel subfamily V member
      1 (TRPV1) expression and S-sulfhydration were detected. In SHRs, systolic blood
      pressure was markedly increased, but the cystathionine-beta-synthase/H2S pathway
      in the carotid sinus was downregulated in comparison to that of Wistar-Kyoto
      rats. Carotid sinus baroreceptor sensitivity in SHRs was reduced, demonstrated by
      the right and upward shift of the functional curve of the carotid baroreceptor.
      Meanwhile, the downregulation of TRPV1 protein was demonstrated in the carotid
      sinus; however, H2S reduced systolic blood pressure but enhanced carotid sinus
      baroreceptor sensitivity in SHRs, along with TRPV1 upregulation in the carotid
      sinus. In contrast, hydroxylamine significantly increased the systolic blood
      pressure of Wistar-Kyoto rats, along with decreased carotid sinus baroreceptor
      sensitivity and reduced TRPV1 protein expression in the carotid sinus.
      Furthermore, H2S-induced enhancement of carotid sinus baroreceptor sensitivity of
      SHRs could be amplified by capsaicin but reduced by capsazepine. Moreover, H2S
      facilitated S-sulfhydration of TRPV1 protein in the carotid sinus of SHRs and
      Wistar-Kyoto rats. CONCLUSIONS: H2S regulated blood pressure via an increase in
      TRPV1 protein expression and its activity to enhance carotid sinus baroreceptor
      sensitivity.

PMID- 28512114
TI  - Associations of Acid Suppressive Therapy With Cardiac Mortality in Heart Failure
      Patients.
AB  - BACKGROUND: It has been recently reported that histamine H2 receptor antagonists
      (H2RAs) are associated with impairment of ventricular remodeling and incident
      heart failure. In addition, favorable pleiotropic effects and adverse effects of
      proton pump inhibitors (PPIs) on cardiovascular disease have also been reported.
      We examined the associations of acid suppressive therapy using H2RAs or PPIs with
      cardiac mortality in patients with heart failure. METHODS AND RESULTS: In total,
      1191 consecutive heart failure patients were divided into 3 groups: a non-acid
      suppressive therapy group (n=363), an H2RA group (n=164), and a PPI group
      (n=664). In the follow-up period (mean 995 days), 169 cardiac deaths occurred. In
      the Kaplan-Meier analysis, cardiac mortality was significantly lower in the PPI
      group than in the H2RA and non-acid suppressive therapy groups (11.0% versus
      21.3% and 16.8%, respectively; log-rank P=0.004). In the multivariable Cox
      proportional hazards analysis, use of PPIs, but not H2RAs, was found to be an
      independent predictor of cardiac mortality (PPIs: hazard ratio 0.488, P=0.002;
      H2RAs: hazard ratio 0.855, P=0.579). The propensity-matched 1:1 cohort was
      assessed based on propensity score (H2RAs, n=164; PPIs, n=164). Cardiac mortality
      was significantly lower in the PPI group than in the H2RA group in the
      postmatched cohort (log-rank P=0.025). In the Cox proportional hazards analysis,
      the use of PPIs was a predictor of cardiac mortality in the postmatched cohort
      (hazard ratio 0.528, P=0.028). CONCLUSIONS: PPIs may be associated with better
      outcome in patients with heart failure.

PMID- 28512116
TI  - Weekday and Survival After Cardiac Surgery-A Swedish Nationwide Cohort Study in
      106 473 Patients.
AB  - BACKGROUND: The purpose of this study was to investigate the association between
      weekday of surgery and survival following cardiac surgery. METHODS AND RESULTS:
      In a nationwide cohort study, we included all patients who underwent cardiac
      surgery in 1999-2013 from the SWEDEHEART (Swedish Web-system for Enhancement and
      Development of Evidence-based care in Heart disease Evaluated According to
      Recommended Therapies) register. All-cause mortality until March 2014 was
      obtained from national registers. The association between weekday of surgery and
      mortality was estimated using Cox regression, and reported as hazard ratios with
      95% CI. We used the restricted mean survival time difference to estimate loss of
      life related to weekday of surgery. Among 106 473 patients, 25 221 (24%), 24 471
      (23%), 22 977 (22%), 20 189 (19%), 9251 (8.7%), and 4364 (4.1%) underwent surgery
      during a Monday, Tuesday, Wednesday, Thursday, Friday, and a Saturday/Sunday,
      respectively. More patients were operated on urgently during Friday to Sunday,
      and unadjusted analyses showed higher early and late mortality in those patients.
      The adjusted hazard ratios (95% CI) were 1.00 (0.89-1.13), 1.00 (0.88-1.12), 1.02
      (0.90-1.16), 1.17 (1.01-1.37), and 1.05 (0.86-1.29) in patients who underwent
      surgery during a Tuesday, Wednesday, Thursday, Friday, and Saturday/Sunday
      compared to a Monday, after 1 year of follow-up conditional on 30-day survival.
      In elective surgery (n=46 146), the 1-year restricted mean survival time
      difference (95% CI) was -0.5 (-1.8-0.8), -0.5 (-1.9-0.8), -1.0 (-2.6-0.5), 0.02 (
      2.2-2.3), and -1.2 (-6.3-3.9) days in patients who underwent surgery during a
      Tuesday, Wednesday, Thursday, Friday, and a Saturday/Sunday, respectively,
      compared to a Monday. CONCLUSIONS: We found no evidence of a clinically relevant
      weekday effect in patents who underwent cardiac surgery in Sweden during a 15
      year period. These data suggest that the early risk and long-term prognosis
      following cardiac surgery was not affected by the weekday of surgery. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT02276950.

PMID- 28512117
TI  - The interaction of MC3R and MC4R with MRAP2, ACTH, alpha-MSH and AgRP in
      chickens.
AB  - The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with
      proopiomelanocortin (POMC)-derived peptides (e.g. alpha-MSH), agouti-related
      protein (AgRP) and melanocortin-2 receptor accessory protein 2 (MRAP2) is
      suggested to play critical roles in energy balance of vertebrates. However,
      evidence on their interaction in birds remains scarce. Our study aims to reveal
      their interaction in chickens and the results showed that (1) chicken (c-)MC3R
      and cMC4R expressed in Chinese hamster ovary (CHO) cells can be activated by
      alpha-MSH and ACTH1-39 equipotently, monitored by a pGL3-CRE-luciferase reporter
      system; (2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2
      homolog), show increased sensitivity to ACTH treatment and thus likely act as
      ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was
      demonstrated by co-immunoprecipitation assay; (3) both cMC3R and cMC4R display
      constitutive activity when expressed in CHO cells, as monitored by dual
      luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive
      activity; (4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also
      antagonizes ACTH/alpha-MSH action on cMC4R/cMC3R, indicating that AgRP functions
      as the inverse agonist and antagonist for both receptors. These findings,
      together with the co-expression of cMC4R, cMC3R, cMRAP2, cAgRP and cPOMC in
      chicken hypothalamus detected by quantitative real-time PCR, suggest that within
      the hypothalamus, alpha-MSH/ACTH, AgRP and MRAP2 may interact at the MC4R(/MC3R)
      interface to control energy balance. Furthermore, our data provide novel proof
      for the involvement of MRAP2 (and MRAP) in fine-tuning the constitutive activity
      and ligand sensitivity and selectivity of both MC3R and MC4R in vertebrates.

PMID- 28512119
TI  - Complementary and integrative medicine in the management of headache.
AB  - Headaches, including primary headaches such as migraine and tension-type
      headache, are a common clinical problem. Complementary and integrative medicine
      (CIM), formerly known as complementary and alternative medicine (CAM), uses
      evidence informed modalities to assist in the health and healing of patients. CIM
      commonly includes the use of nutrition, movement practices, manual therapy,
      traditional Chinese medicine, and mind-body strategies. This review summarizes
      the literature on the use of CIM for primary headache and is based on five meta
      analyses, seven systematic reviews, and 34 randomized controlled trials (RCTs).
      The overall quality of the evidence for CIM in headache management is generally
      low and occasionally moderate. Available evidence suggests that traditional
      Chinese medicine including acupuncture, massage, yoga, biofeedback, and
      meditation have a positive effect on migraine and tension headaches. Spinal
      manipulation, chiropractic care, some supplements and botanicals, diet
      alteration, and hydrotherapy may also be beneficial in migraine headache. CIM has
      not been studied or it is not effective for cluster headache. Further research is
      needed to determine the most effective role for CIM in patients with headache.

PMID- 28512118
TI  - Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma
      cells via the EGFR/Ca2+/calpain/ITGbeta4 axis.
AB  - Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) promotes the
      motility of nasopharyngeal carcinoma (NPC) cells. Previously, we have shown that
      the localization of integrin beta4 (ITGbeta4) is regulated by LMP2A, with
      ITGbeta4 concentrated at the cellular protrusions in LMP2A-expressing NPC cells.
      In the present study, we aim to further investigate mechanisms involved in this
      process and its contribution to cell motility. We show that expression of LMP2A
      was correlated with increased epidermal growth factor receptor (EGFR) activation,
      elevated levels of intracellular Ca2+, calpain activation and accelerated
      cleavage of ITGbeta4. Activation of EGFR and calpain activity was responsible for
      a redistribution of ITGbeta4 from the basal layer of NPC cells to peripheral
      membrane structures, which correlated with an increased migratory capacity of NPC
      cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was
      downregulated in NPC primary tumors. In conclusion, our results point to LMP2A
      mediated targeting of the EGFR/Ca2+/calpain/ITGbeta4 signaling system as a
      mechanism underlying the increased motility of NPC cells. We suggest that calpain
      facilitated cleavage of ITGbeta4 contributes to the malignant phenotype of NPC
      cells.

PMID- 28512120
TI  - Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.
AB  - BACKGROUND: A clinical classification system has been developed to define the
      severity and predict the prognosis of subjects with non-cystic fibrosis (CF)
      bronchiectasis. We aimed to identify laboratory parameters that are correlated
      with the bronchiectasis severity index (BSI) and FACED score. METHODS: The
      medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED
      scores could be calculated were retrospectively reviewed. The correlations
      between the laboratory parameters and BSI or FACED score were assessed, and
      multiple-linear regression analysis was performed to identify variables
      independently associated with BSI and FACED score. An additional subgroup
      analysis was performed according to sex. RESULTS: Among all of the enrolled
      subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED
      scores were 9.43 +/- 3.81 and 1.92 +/- 1.59, respectively. The serum albumin
      level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r =
      0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were
      significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and
      bilirubin level (r = -0.25) showed a significant correlation with the FACED
      score. Multiple-linear regression analysis showed that the serum bilirubin level
      was independently associated with BSI, and the serum albumin level was
      independently associated with both scoring systems. Subgroup analysis revealed
      that the level of uric acid was also a significant variable independently
      associated with the BSI in male bronchiectasis subjects. CONCLUSIONS: Several
      laboratory variables were identified as possible prognostic factors for non-CF
      bronchiectasis. Among them, the serum albumin level exhibited the strongest
      correlation and was identified as an independent variable associated with the BSI
      and FACED scores.

PMID- 28512122
TI  - Labour calls for inquiry into NHS cyber-attack.

PMID- 28512121
TI  - Agricultural pest control with CRISPR-based gene drive: time for public debate:
      Should we use gene drive for pest control?

PMID- 28512123
TI  - Treatment of severe hypocalcaemia due to osteoblastic metastases in a patient
      with post-thyroidectomy hypoparathyroidism with 153Sm-EDTMP.
AB  - Symptomatic hypocalcaemia is an uncommon finding in patients with malignant
      tumours. We describe a patient with advanced metastatic breast cancer who
      developed severe hypocalcaemia caused by the combination of osteoblastic
      metastases and a permanent postoperative hypoparathyroidism. The patient failed
      to be treated with the conventional replacement therapy and was submitted
      effectively to radionucleotide therapy with 153Sm.

PMID- 28512124
TI  - Use of propranolol in a remote region of rural Guatemala to treat a large facial
      infantile haemangioma.
AB  - We present a female infant with a right-sided facial and neck haemangioma, from a
      remote, resource-poor community in rural Guatemala. She received first-line
      treatment, propranolol, with marked reduction in tumour size and erythema.
      Treatment was stopped after 35 weeks due to recurrent diarrhoea and sustained
      weight loss. Propranolol can be used to safely treat infants with haemangiomas in
      remote, rural communities if there is adequate follow-up, education and
      communication. Periocular haemangiomas should be treated promptly to avoid visual
      impairment. Infants with large facial haemangiomas should be screened for
      Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac anomalies, and
      Eye anomalies (PHACE) syndrome, and specialists should be involved. The case also
      highlights the difficulty of providing treatment for a complex illness when basic
      health needs, such as food security and water sanitation, are limited.

PMID- 28512125
TI  - Full-thickness gaping wound in the inguinal region of prenatal origin in an
      extremely premature baby.

PMID- 28512126
TI  - Tumor-associated myoepithelial cells promote the invasive progression of ductal
      carcinoma in situ through activation of TGFbeta signaling.
AB  - The normal myoepithelium has a tumor-suppressing nature and inhibits the
      progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma
      (IDC). Conversely, a growing number of studies have shown that tumor-associated
      myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of
      tumor-associated myoepithelial cells in the DCIS-to-IDC development remains
      undefined. To address this, we explored the role of tumor-associated
      myoepithelial cells in the DCIS-to-IDC progression. We developed a direct
      coculture system to study the cell-cell interactions between DCIS cells and tumor
      associated myoepithelial cells. Coculture studies indicated that tumor-associated
      myoepithelial cells promoted the invasive progression of a DCIS cell model in
      vitro, and mechanistic studies revealed that the interaction with DCIS cells
      stimulated tumor-associated myoepithelial cells to secrete TGFbeta1, which
      subsequently contributed to activating the TGFbeta/Smads pathway in DCIS cells.
      We noted that activation of the TGFbeta signaling pathway promoted the epithelial
      mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS
      cells. Importantly, xenograft studies further demonstrated that tumor-associated
      myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we
      found that TGFbeta-mediated induction of oncogenic miR-10b-5p expression and down
      regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to
      the invasive progression of DCIS. Our findings provide the first experimental
      evidence to directly support the paradigm that altered DCIS-associated
      myoepithelial cells promote the invasive progression of DCIS into IDC via TGFbeta
      signaling activation.

PMID- 28512128
TI  - Refined topology model of the STT3/Stt3 protein subunit of the
      oligosaccharyltransferase complex.
AB  - The oligosaccharyltransferase complex, localized in the endoplasmic reticulum
      (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of
      numerous protein substrates. The membrane protein STT3 is a highly conserved part
      of the oligosaccharyltransferase and likely contains the active site of the
      complex. However, understanding the catalytic determinants of this system has
      been challenging, in part because of a discrepancy in the structural topology of
      the bacterial versus eukaryotic proteins and incomplete information about the
      mechanism of membrane integration. Here, we use a glycosylation mapping approach
      to investigate these questions. We measured the membrane integration efficiency
      of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a
      refined topology of the N-terminal half of the mouse STT3-A. Our results show
      that most of the STT3 TMDs are well inserted into the ER membrane on their own or
      in the presence of the natural flanking residues. However, for the mouse STT3-A
      hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured
      reduced insertion efficiency into the ER membrane. Furthermore, we mapped the
      first half of the STT3-A protein, finding two extra hydrophobic domains between
      the third and the fourth TMD. This result indicates that the eukaryotic STT3 has
      13 transmembrane domains, consistent with the structure of the bacterial homolog
      of STT3 and setting the stage for future combined efforts to interrogate this
      fascinating system.

PMID- 28512127
TI  - A structure-derived snap-trap mechanism of a multispecific serpin from the
      dysbiotic human oral microbiome.
AB  - Enduring host-microbiome relationships are based on adaptive strategies within a
      particular ecological niche. Tannerella forsythia is a dysbiotic member of the
      human oral microbiome that inhabits periodontal pockets and contributes to
      chronic periodontitis. To counteract endopeptidases from the host or microbial
      competitors, T. forsythia possesses a serpin-type proteinase inhibitor called
      miropin. Although serpins from animals, plants, and viruses have been widely
      studied, those from prokaryotes have received only limited attention. Here we
      show that miropin uses the serpin-type suicidal mechanism. We found that, similar
      to a snap trap, the protein transits from a metastable native form to a relaxed
      triggered or induced form after cleavage of a reactive-site target bond in an
      exposed reactive-center loop. The prey peptidase becomes covalently attached to
      the inhibitor, is dragged 75 A apart, and is irreversibly inhibited. This
      coincides with a large conformational rearrangement of miropin, which inserts the
      segment upstream of the cleavage site as an extra beta-strand in a central beta
      sheet. Standard serpins possess a single target bond and inhibit selected
      endopeptidases of particular specificity and class. In contrast, miropin uniquely
      blocked many serine and cysteine endopeptidases of disparate architecture and
      substrate specificity owing to several potential target bonds within the reactive
      center loop and to plasticity in accommodating extra beta-strands of variable
      length. Phylogenetic studies revealed a patchy distribution of bacterial serpins
      incompatible with a vertical descent model. This finding suggests that miropin
      was acquired from the host through horizontal gene transfer, perhaps facilitated
      by the long and intimate association of T. forsythia with the human gingiva.

PMID- 28512129
TI  - Mammalian O-mannosylation of cadherins and plexins is independent of protein O
      mannosyltransferases 1 and 2.
AB  - Protein O-mannosylation is found in yeast and metazoans, and a family of
      conserved orthologous protein O-mannosyltransferases is believed to initiate this
      important post-translational modification. We recently discovered that the
      cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved
      residues in specific extracellular cadherin domains, and it was suggested that
      the function of E-cadherin was dependent on the O-Man glycans. Deficiencies in
      enzymes catalyzing O-Man biosynthesis, including the two human protein O
      mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular
      dystrophies designated alpha-dystroglycanopathies, because deficient O-Man
      glycosylation of alpha-dystroglycan disrupts laminin interaction with alpha
      dystroglycan and the extracellular matrix. To explore the functions of O-Man
      glycans on cadherins and protocadherins, we used a combinatorial gene-editing
      strategy in multiple cell lines to evaluate the role of the two POMTs initiating
      O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O
      mannose beta-1,2-N-acetylglucosaminyltransferase, POMGnT1. Surprisingly, O
      mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2
      in contrast to alpha-dystroglycan, and moreover, the O-Man glycans on cadherins
      are not elongated. Thus, the classical and evolutionarily conserved POMT O
      mannosylation pathway is essentially dedicated to alpha-dystroglycan and a few
      other proteins, whereas a novel O-mannosylation process in mammalian cells is
      predicted to serve the large cadherin superfamily and other proteins.

PMID- 28512131
TI  - H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase.
AB  - Buildup of hydrogen sulfide (H2S), which functions as a signaling molecule but is
      toxic at high concentrations, is averted by its efficient oxidation by the
      mitochondrial sulfide oxidation pathway. The first step in this pathway is
      catalyzed by a flavoprotein, sulfide quinone oxidoreductase (SQR), which converts
      H2S to a persulfide and transfers electrons to coenzyme Q via a flavin cofactor.
      All previous studies on human SQR have used detergent-solubilized protein. Here,
      we embedded human SQR in nanodiscs (ndSQR) and studied highly homogenous
      preparations by steady-state and rapid-kinetics techniques. ndSQR exhibited
      higher catalytic rates in its membranous environment than in its solubilized
      state. Stopped-flow spectroscopic data revealed that transfer of the sulfane
      sulfur from an SQR-bound cysteine persulfide intermediate to a small-molecule
      acceptor is the rate-limiting step. The physiological acceptor of sulfane sulfur
      from SQR has been the subject of controversy; we report that the kinetic analysis
      of ndSQR is consistent with glutathione rather than sulfite being the predominant
      acceptor at physiologically relevant concentrations of the respective
      metabolites. The identity of the acceptor has an important bearing on how the
      sulfide oxidation pathway is organized. Our data are more consistent with the
      reaction sequence for sulfide oxidation being: H2S -> glutathione persulfide ->
      sulfite -> sulfate, than with a more convoluted route that would result if
      sulfite were the primary acceptor of sulfane sulfur. In summary, nanodisc
      incorporated human SQR exhibits enhanced catalytic performance, and pre-steady
      state kinetics characterization of the complete SQR catalytic cycle indicates
      that GSH serves as the physiologically relevant sulfur acceptor.

PMID- 28512132
TI  - Abortion by telemedicine: an equitable option for Irish women.

PMID- 28512134
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Suicide risk in patients with diabetes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies investigating the risk of suicide in diabetes
      patients reported controversial findings. We did a systematic review and meta
      analysis to comprehensively estimate the risk and incidence rate of suicide in
      diabetic patients. METHODS: PubMed, EMBASE and PsycINFO were searched for
      eligible studies. Random-effects meta-analysis was used to calculate the relative
      risk (RR) and the incidence rate of suicide in diabetes patients. We also
      calculated the proportion of deaths attributable to suicide among diabetes
      patients. RESULTS: 54 studies were finally included, including 28 studies on the
      suicide risk associated with diabetes, 47 studies on the incidence rate of
      suicide and 45 studies on the proportion of deaths attributable to suicide. Meta
      analysis showed that diabetes could significantly increase the risk of suicide
      (RR = 1.56; 95% CI: 1.29-1.89; P < 0.001). Subgroup analysis showed that the RR
      of suicide associated with type 1 diabetes was 2.25 (95% CI: 1.50-3.38; P <
      0.001). The pooled incidence rate of suicide in patients with diabetes was 2.35
      per 10 000 person-years (95% CI: 1.51-3.64). The pooled proportions of long-term
      deaths attributable to suicide in type 1 diabetes patients and type 2 diabetes
      patients were 7.7% (95% CI: 6.0-9.8) and 1.3% (95% CI: 0.6-2.6), respectively.
      CONCLUSION: This meta-analysis suggests that diabetes can significantly increase
      the risk of suicide. Suicide has an obvious contribution to mortality in diabetic
      patients, especially among type 1 diabetes patients. Effective strategies to
      decrease suicide risk and improve mental health outcomes in diabetes patients are
      needed.

PMID- 28512130
TI  - Combination therapy with octyl gallate and ferulic acid improves cognition and
      neurodegeneration in a transgenic mouse model of Alzheimer's disease.
AB  - To date, there is no effective Alzheimer's disease (AD)-modifying therapy.
      Nonetheless, combination therapy holds promise, and nutraceuticals (natural
      dietary compounds with therapeutic properties) and their synthetic derivatives
      are well-tolerated candidates. We tested whether combination therapy with octyl
      gallate (OG) and ferulic acid (FA) improves cognition and mitigates AD-like
      pathology in the presenilin-amyloid beta-protein precursor (PSAPP) transgenic
      mouse model of cerebral amyloidosis. One-year-old mice with established beta
      amyloid plaques received daily doses of OG and FA alone or in combination for 3
      months. PSAPP mice receiving combination therapy had statistically significant
      improved cognitive function versus OG or FA single treatment on some (but not
      all) measures. We also observed additional statistically significant reductions
      in brain parenchymal and cerebral vascular beta-amyloid deposits as well as brain
      amyloid beta-protein abundance in OG- plus FA-treated versus singly-treated PSAPP
      mice. These effects coincided with enhanced nonamyloidogenic amyloid beta-protein
      precursor (APP) cleavage, increased alpha-secretase activity, and beta-secretase
      inhibition. We detected elevated expression of nonamyloidogenic soluble APP-alpha
      and the alpha-secretase candidate, a disintegrin and metalloproteinase domain
      containing protein 10. Correspondingly, amyloidogenic beta-carboxyl-terminal APP
      fragment and beta-site APP-cleaving enzyme 1 expression levels were reduced. In
      parallel, the ratio of beta- to alpha-carboxyl-terminal APP fragment was
      decreased. OG and FA combination therapy strikingly attenuated neuroinflammation,
      oxidative stress, and synaptotoxicity. Co-treatment afforded additional
      statistically significant benefits on some, but not all, of these outcome
      measures. Taken together, these data provide preclinical proof-of-concept for AD
      combination therapy.

PMID- 28512133
TI  - Quality of compounded hydrocortisone capsules used in the treatment of children.
AB  - OBJECTIVES: Due to the lack of paediatric-licensed formulations, children are
      often treated with individualized pharmacy-compounded adult medication. An
      international web-based survey about the types of medication in children with
      adrenal insufficiency (AI) revealed that the majority of paediatric physicians
      are using pharmacy-compounded medication to treat children with AI. Observations
      of loss of therapy control in children with congenital adrenal hyperplasia with
      compounded hydrocortisone capsules and regained control after prescribing a new
      hydrocortisone batch led to this 'real world' evaluation of pharmacy-compounded
      paediatric hydrocortisone capsules. METHODS: Capsule samples were collected
      randomly from volunteering parents of treated children suffering from congenital
      adrenal hyperplasia from all over Germany. Analysis of net mass and
      hydrocortisone content by high-performance liquid chromatography with ultraviolet
      (HPLC-UV) detection method was performed based on the European Pharmacopeia.
      RESULTS: In a total of 61 batches that were sent, 5 batches could not be analysed
      because of missing dose information, insufficient number of capsules or were not
      possible to be evaluated. Fifty-six batches containing 1125 capsules were
      evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass
      or drug content and additional 3.6% failed because they did not contain the
      labelled drug. CONCLUSIONS: Compounded medication is a possible cause of
      variation of steroid doses in children with adrenal insufficiency or congenital
      adrenal hyperplasia, putting these vulnerable patients at risk of poor disease
      control and adrenal crisis. These data may apply to other individualized
      compounded oral medication as well, emphasizing the need for development of
      licensed paediatric formulations approved by regulatory authorities.

PMID- 28512135
TI  - Critical thinking in healthcare and education.

PMID- 28512136
TI  - Physician age and patient outcomes.

PMID- 28512137
TI  - Keep within target range of blood oxygen levels, new guideline recommends.

PMID- 28512138
TI  - Factors Predicting Parent Anxiety Around Infant and Toddler Postoperative and
      Pain.
AB  - BACKGROUND AND OBJECTIVES: Understanding of parent anxiety and its effect on
      infant postoperative pain is limited. We sought to identify psychological factors
      associated with preoperative anxiety for parents of infants and toddlers
      undergoing elective surgery and to determine whether parent anxiety is associated
      with child postoperative pain. METHODS: This was a prospective cohort study of
      consecutively eligible patients aged <=18 months undergoing craniofacial surgery
      and their parents. Preoperative parent assessment included anxiety, coping,
      parent health locus of control, and self-efficacy. Postoperative inpatient child
      pain scores and medication use were collected. Analyses included hierarchical
      multivariable logistic and linear regression models. RESULTS: Parents (n = 71,
      90% female) of young children (mean age 6.6 months) undergoing cleft lip or
      palate (n = 59) or cranial vault repair (n = 13) were enrolled. Maladaptive
      coping (odds ratio 1.3; 95% confidence interval, 1.1-1.6), low parent self
      efficacy (odds ratio 2.4; 95% confidence interval, 1.3-4.5), and external locus
      of control (odds ratio 1.74; 95% confidence interval, 1.1-2.9) were independently
      associated with high parental anxiety. The adjusted odds of moderate/severe
      parent anxiety was 3.6 (95% confidence interval, 1.5-9.1) higher with each SD
      increase in maladaptive coping. High parental anxiety was correlated with
      significantly higher hospital mean child pain scores (1.87 points on 0-10 scale;
      95% confidence interval, 0.42-3.70; P = .045). CONCLUSIONS: Coping and self
      efficacy are modifiable factors that contribute to parent anxiety before and
      during hospitalization and may be targets for intervention. Infants and toddlers
      undergoing elective craniofacial surgery with highly anxious parents may be at
      greater risk for higher postoperative pain.

PMID- 28512141
TI  - Oncogene-inducible organoids as a miniature platform to assess cancer
      characteristics.
AB  - Direct effects of oncogenic proteins or inhibitor treatments on signaling
      pathways are difficult to assess in transgenic mice. In this issue, Riemer et al.
      (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610058) demonstrate that
      oncogene-inducible organoids offer the experimental versatility of two
      dimensional cell lines, while closely representing the in vivo situation.

PMID- 28512142
TI  - A well-known potassium channel plays a critical role in lysosomes.
AB  - Whole-endolysosome patch clamping presents new opportunities to identify and
      characterize channels pivotal for these acidic organelles. In this issue (Wang et
      al., 2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612123), the
      identification of a role for the large conductance calcium-activated potassium
      channel brings new thinking about regulation of lysosome membrane potential and
      function.

PMID- 28512139
TI  - A genome-wide association meta-analysis on lipoprotein (a) concentrations
      adjusted for apolipoprotein (a) isoforms.
AB  - High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for
      cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle
      IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a)
      concentrations using data from five genome-wide association studies (n = 13,781).
      We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to
      be significantly associated with Lp(a) concentrations. We also adjusted for
      apo(a) isoforms to identify loci affecting Lp(a) levels independently from them,
      which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seven SNPs
      showed a genome-wide significant association with coronary artery disease (CAD)
      risk. A rare SNP (rs186696265; MAF ~1%) showed the highest effect on Lp(a) and
      was also associated with increased risk of CAD (odds ratio = 1.73, P = 3.35 * 10
      30). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number
      of Lp(a)-increasing alleles. We found the APOE2-determining allele of rs7412 to
      be significantly associated with Lp(a) concentrations (P = 3.47 * 10-10). Each
      APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ~15% of the
      population's mean values. Performing a gene-based test of association, including
      suspected Lp(a) receptors and regulators, resulted in one significant association
      of the TLR2 gene with Lp(a) (P = 3.4 * 10-4). In summary, we identified a large
      number of independent SNPs in the LPA gene region, as well as the APOE2 allele,
      to be significantly associated with Lp(a) concentrations.

PMID- 28512143
TI  - Diverse roles of guanine nucleotide exchange factors in regulating collective
      cell migration.
AB  - Efficient collective migration depends on a balance between contractility and
      cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication,
      all controlled by GTPases of the RHO family. By comprehensive screening of
      guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell
      monolayers, we identified GEFs that are required for collective migration at
      large, such as SOS1 and beta-PIX, and RHOA GEFs that are implicated in
      intercellular communication. Down-regulation of the latter GEFs differentially
      enhanced front-to-back propagation of guidance cues through the monolayer and was
      mirrored by down-regulation of RHOA expression and myosin II activity. Phenotype
      based clustering of knockdown behaviors identified RHOA-ARHGEF18 and ARHGEF3
      ARHGEF28-ARHGEF11 clusters, indicating that the latter may signal through other
      RHO-family GTPases. Indeed, knockdown of RHOC produced an intermediate between
      the two phenotypes. We conclude that for effective collective migration, the RHOA
      GEFs -> RHOA/C -> actomyosin pathways must be optimally tuned to compromise
      between generation of motility forces and restriction of intercellular
      communication.

PMID- 28512144
TI  - TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle
      formation.
AB  - XMAP215, CLASP, and Crescerin use arrayed tubulin-binding tumor overexpressed
      gene (TOG) domains to modulate microtubule dynamics. We hypothesized that TOGs
      have distinct architectures and tubulin-binding properties that underlie each
      family's ability to promote microtubule polymerization or pause. As a model, we
      investigated the pentameric TOG array of a Drosophila melanogaster XMAP215
      member, Msps. We found that Msps TOGs have distinct architectures that bind
      either free or polymerized tubulin, and that a polarized array drives microtubule
      polymerization. An engineered TOG1-2-5 array fully supported Msps-dependent
      microtubule polymerase activity. Requisite for this activity was a TOG5-specific
      N-terminal HEAT repeat that engaged microtubule lattice-incorporated tubulin.
      TOG5-microtubule binding maintained mitotic spindle formation as deleting or
      mutating TOG5 compromised spindle architecture and increased the mitotic index.
      Mad2 knockdown released the spindle assembly checkpoint triggered when TOG5
      microtubule binding was compromised, indicating that TOG5 is essential for
      spindle function. Our results reveal a TOG5-specific role in mitotic fidelity and
      support our hypothesis that architecturally distinct TOGs arranged in a sequence
      specific order underlie TOG array microtubule regulator activity.

PMID- 28512146
TI  - Science Signaling Podcast for 16 May 2017: Vibrio rewires host cells.
AB  - This Podcast features a conversation with Kim Orth and Nicole De Nisco, authors
      of a Research Resource that appears in the 16 May 2017 issue of Science
      Signaling, about how the marine bacterium Vibrio parahaemolyticus rewires host
      cell signaling networks. V. parahaemolyticus thrives in warm brackish waters and
      infects both shellfish and finfish. This bacterium causes gastroenteritis when
      humans consume contaminated seafood that is raw or undercooked. V.
      parahaemolyticus delivers virulence factors into host cells through two different
      type 3 secretion systems (T3SSes). Whereas T3SS2 mediates gastroenteritis, T3SS1
      is required for the bacterium to survive in its natural environment and delivers
      virulence factors that target conserved cellular processes. De Nisco et al
      examined transcriptional changes in human cells infected with a strain of V.
      parahaemolyticus that lacked T3SS2 but had an intact T3SS1. They found that the
      virulence factors delivered through T3SS1 initially induced transcriptional
      changes that promoted cell survival, then later repressed prosurvival signaling
      to induce cell death.Listen to Podcast.

PMID- 28512145
TI  - The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to
      subvert cell death and activate cell survival pathways.
AB  - Bacterial effectors potently manipulate host signaling pathways. The marine
      bacterium Vibrio parahaemolyticus (V. para) delivers effectors into host cells
      through two type 3 secretion systems (T3SSs). T3SS1 is vital for V. para survival
      in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts.
      Although the natural host is undefined, T3SS1 effectors attack highly conserved
      cellular processes and pathways to orchestrate nonapoptotic cell death. To
      understand how the concerted action of T3SS1 effectors globally affects host cell
      signaling, we compared gene expression changes over time in primary fibroblasts
      infected with V. para that have a functional T3SS1 (T3SS1+) to those in cells
      infected with V. para lacking T3SS1 (T3SS1-). Overall, the host transcriptional
      response to both T3SS1+ and T3SS1-V. para was rapid, robust, and temporally
      dynamic. T3SS1 rewired host gene expression by specifically altering the
      expression of 398 genes. Although T3SS1 effectors targeted host cells at the
      posttranslational level to cause cytotoxicity, V. para T3SS1 also precipitated a
      host transcriptional response that initially activated cell survival and
      repressed cell death networks. The increased expression of several key
      prosurvival transcripts mediated by T3SS1 depended on a host signaling pathway
      that is silenced posttranslationally later in infection. Together, our analysis
      reveals a complex interplay between the roles of T3SS1 as both a transcriptional
      and posttranslational manipulator of host cell signaling.

PMID- 28512148
TI  - Erratum for the Research Article: "Reactive oxygen species induce virus
      independent MAVS oligomerization in systemic lupus erythematosus" by I. A.
      Buskiewicz, T. Montgomery, E. C. Yasewicz, S. A. Huber, M. P. Murphy, R. C.
      Hartley, R. Kelly, M. K. Crow, A. Perl, R. C. Budd, A. Koenig.

PMID- 28512149
TI  - Quorum sensing to repress virulence.
AB  - A quorum-sensing system of an insect endosymbiont enables the bacterium to
      establish persistent infection by inhibiting the expression of virulence genes.

PMID- 28512147
TI  - Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model
      and improves maternal and fetal outcomes.
AB  - Placental activation of the renin-angiotensin system (RAS) plays a key role in
      the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to
      affect placental angiogenesis, which is critical for preventing preeclampsia
      pathology. We examined the role of ROS in preeclampsia by genetically modifying
      the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model
      of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular
      antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved
      maternal and fetal survival, ameliorated intra-uterine growth retardation, and
      augmented oxidative DNA damage. Furthermore, the placentas of Nrf2-deficient mice
      had increased endothelial cell proliferation with dense vascular networks. In
      contrast, the placentas of preeclamptic mice with overactive Nrf2 showed
      repressed angiogenesis, which was associated with decreased expression of genes
      encoding angiogenic chemokines and cytokines. Our findings support the notion
      that ROS-mediated signaling is essential for maintaining placental angiogenesis
      in preeclampsia and may provide mechanistic insight into the negative results of
      clinical trials for antioxidants in preeclampsia.

PMID- 28512153
TI  - New connections: The duality of ROS in angiogenesis.
AB  - Depending on the tissue and context, ROS can either stimulate or suppress blood
      vessel formation.

PMID- 28512154
TI  - Glucose autoregulation is the dominant component of the hormone-independent
      counterregulatory response to hypoglycemia in the conscious dog.
AB  - The contribution of hormone-independent counterregulatory signals in defense of
      insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted
      conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold
      basal. Either euglycemia was maintained (group 1) or hypoglycemia (~45 mg/dl) was
      allowed to occur. There were three hypoglycemic groups: one in which hepatic
      autoregulation against hypoglycemia occurred in the absence of sympathetic
      nervous system input (group 2), one in which autoregulation occurred in the
      presence of norepinephrine (NE) signaling to fat and muscle (group 3), and one in
      which autoregulation occurred in the presence of NE signaling to fat, muscle, and
      liver (group 4). Average net hepatic glucose balance (NHGB) during the last hour
      for groups 1-4 was -0.7 +/- 0.1, 0.3 +/- 0.1 (P < 0.01 vs. group 1), 0.7 +/- 0.1
      (P = 0.01 vs. group 2), and 0.8 +/- 0.1 (P = 0.7 vs. group 3) mg.kg-1.min-1,
      respectively. Hypoglycemia per se (group 2) increased NHGB by causing an
      inhibition of net hepatic glycogen synthesis. NE signaling to fat and muscle
      (group 3) increased NHGB further by mobilizing gluconeogenic precursors resulting
      in a rise in gluconeogenesis. Lowering glucose per se decreased nonhepatic
      glucose uptake by 8.9 mg.kg-1.min-1, and the addition of increased neural
      efferent signaling to muscle and fat blocked glucose uptake further by 3.2 mg.kg
      1.min-1 The addition of increased neural efferent input to liver did not affect
      NHGB or nonhepatic glucose uptake significantly. In conclusion, even in the
      absence of increases in counterregulatory hormones, the body can defend itself
      against hypoglycemia using glucose autoregulation and increased neural efferent
      signaling, both of which stimulate hepatic glucose production and limit glucose
      utilization.

PMID- 28512156
TI  - Effects of metformin on compensatory pancreatic beta-cell hyperplasia in mice fed
      a high-fat diet.
AB  - Metformin has been widely used for the treatment of type 2 diabetes. However, the
      effect of metformin on pancreatic beta-cells remains controversial. In this
      study, we investigated the impacts of treatment with metformin on pancreatic beta
      cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive beta
      cell replication. An 8-wk treatment with metformin improved insulin resistance
      and suppressed the compensatory beta-cell hyperplasia induced by HFD-feeding. In
      contrast, the increment in beta-cell mass arising from 60 wk of HFD feeding was
      similar in mice treated with and those treated without metformin. Interestingly,
      metformin suppressed beta-cell proliferation induced by 1 wk of HFD feeding
      without any changes in insulin resistance. Metformin directly suppressed glucose
      induced beta-cell proliferation in islets and INS-1 cells in accordance with a
      reduction in mammalian target of rapamycin phosphorylation. Taken together,
      metformin suppressed HFD-induced beta-cell proliferation independent of the
      improvement of insulin resistance, partly via direct actions.

PMID- 28512155
TI  - Functional high-intensity training improves pancreatic beta-cell function in
      adults with type 2 diabetes.
AB  - Type 2 diabetes (T2D) is characterized by reductions in beta-cell function and
      insulin secretion on the background of elevated insulin resistance. Aerobic
      exercise has been shown to improve beta-cell function, despite a subset of T2D
      patients displaying "exercise resistance." Further investigations into the
      effectiveness of alternate forms of exercise on beta-cell function in the T2D
      patient population are needed. We examined the effect of a novel, 6-wk CrossFit
      functional high-intensity training (F-HIT) intervention on beta-cell function in
      12 sedentary adults with clinically diagnosed T2D (54 +/- 2 yr, 166 +/- 16 mg/dl
      fasting glucose). Supervised training was completed 3 days/wk, comprising
      functional movements performed at a high intensity in a variety of 10- to 20-min
      sessions. All subjects completed an oral glucose tolerance test and
      anthropometric measures at baseline and following the intervention. The mean
      disposition index, a validated measure of beta-cell function, was significantly
      increased (PRE: 8.4 +/- 3.1, POST: 11.5 +/- 3.5, P = 0.02) after the
      intervention. Insulin processing inefficiency in the beta-cell, expressed as the
      fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 +/- 0.37, POST:
      1.78 +/- 0.30, P = 0.04). Increased beta-cell function during the early-phase
      response to glucose correlated significantly with reductions in abdominal body
      fat (R2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase (R2 = 0.55, P
      = 0.006). Mean total body-fat percentage decreased significantly (Delta: -1.17
      0.30%, P = 0.003), whereas lean body mass was preserved (Delta: +0.05 +/- 0.68
      kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for
      improving beta-cell function in adults with T2D.

PMID- 28512157
TI  - IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium
      for antigen uptake.
AB  - Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue
      depending on the situation; therefore, IL-22 signaling needs to be tightly
      regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22
      signaling. It is expressed in intestinal and lymphoid tissues, although its
      precise distribution and roles have remained unclear. In this study, we show that
      IL-22BP is highly expressed by CD11b+CD8alpha- dendritic cells in the
      subepithelial dome region of Peyer's patches (PPs). We found that IL-22BP blocks
      IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs,
      indicating that IL-22BP plays a role in regulating the characteristics of the
      FAE. As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered
      properties such as the enhanced expression of mucus and antimicrobial proteins as
      well as prominent fucosylation, which are normally suppressed in FAE.
      Additionally, Il22ra2-/- mice exhibited the decreased uptake of bacterial
      antigens into PPs without affecting M cell function. Our present study thus
      demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE
      gene expression and function.

PMID- 28512158
TI  - Association between changes in fat distribution and biomarkers for breast cancer.
AB  - We assessed the associations between changes in total and abdominal fat and
      changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In
      the SHAPE-2 trial, 243 postmenopausal overweight women were included. The
      intervention in this trial consisted of 5-6 kg weight loss either by diet only or
      exercise plus diet. After 16 weeks, we measured serum sex hormones, inflammatory
      markers, total body fat (measured by DEXA scan) and intra and subcutaneous
      abdominal fat (measured by MRI). Associations between changes in different body
      fat depots and biomarkers were analysed by linear regression using the study
      cohort irrespective of randomisation to make maximal use of the distribution of
      changes in fat measures. We found that a loss in total body fat was associated
      with favourable changes in free oestradiol, free testosterone, leptin and sex
      hormone binding globulin (SHBG). The loss of intra-abdominal fat was associated
      with a decrease in free testosterone, hsCRP and leptin, and an increase in SHBG.
      In the multivariable analysis, the best fitted models for the biomarkers free
      oestradiol, SHBG leptin and adiponectin included only total body fat. For free
      testosterone, this was subcutaneous abdominal fat, and for hsCRP and IL-6, only
      intra-abdominal fat change was important. For IL-6 and adiponectin, however,
      associations were weak and not significant. We conclude that, in our population
      of healthy overweight postmenopausal women, loss of fat at different body
      locations was associated with changes in different types of biomarkers, known to
      be related to risk of breast cancer.

PMID- 28512159
TI  - Employing Extracellular Volume Cardiovascular Magnetic Resonance Measures of
      Myocardial Fibrosis to Foster Novel Therapeutics.
AB  - Quantifying myocardial fibrosis (MF) with myocardial extracellular volume
      measures acquired during cardiovascular magnetic resonance promises to transform
      clinical care by advancing pathophysiologic understanding and fostering novel
      therapeutics. Extracellular volume quantifies MF by measuring the extracellular
      compartment depicted by the myocardial uptake of contrast relative to plasma. MF
      is a key domain of dysfunctional but viable myocardium among others (eg,
      microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction). Although
      anatomically distinct, these domains may functionally interact. MF represents
      pathological remodeling in the heart associated with cardiac dysfunction and
      adverse outcomes likely mediated by interactions with the microvasculature and
      the cardiomyocyte. Reversal of MF improves key measures of cardiac dysfunction,
      so reversal of MF represents a likely mechanism for improved outcomes. Instead of
      characterizing the myocardium as homogenous tissue and using important yet still
      generic descriptors, such as thickness (hypertrophy) and function (diastolic or
      systolic), which lack mechanistic specificity, paradigms of cardiac disease have
      evolved to conceptualize myocardial disease and patient vulnerability based on
      the extent of disease involving its various compartments. Specifying myocardial
      compartmental involvement may then implicate cellular/molecular disease pathways
      for treatment and targeted pharmaceutical development and above all highlight the
      role of the cardiac-specific pathology in heart failure among myriad other
      changes in the heart and beyond. The cardiology community now requires phase 2
      and 3 clinical trials to examine strategies for the regression/prevention of MF
      and eventually biomarkers to identify MF without reliance on cardiovascular
      magnetic resonance. It seems likely that efficacious antifibrotic therapy will
      improve outcomes, but definitive data are needed.

PMID- 28512160
TI  - Improving the Impact of Peritoneal Dialysis Research.

PMID- 28512161
TI  - Should Nephrologists Promote Peritoneal Dialysis as a Bridge to Transplantation?

PMID- 28512162
TI  - Increase in Extracellular Hydration Status After Initiating Peritoneal Dialysis
      Electively.
AB  - Renal replacement therapy is designed to treat uremic symptoms and correct
      hypervolemia. We hypothesized that starting peritoneal dialysis (PD) should
      reduce overhydration, and we measured body composition and hydration status using
      bioimpedance in PD patients prior to training and then at the first assessment of
      peritoneal membrane function. We studied 100 consecutive patients with a planned
      start to PD, without peritoneal infections or mechanical catheter problems, mean
      age 54.7 +/- 17.1 years, 57% male and 25% diabetic. Extracellular water (ECW)
      overhydration increased from -0.06 (-1.21 to 0.97) L to 0.96 (0.50 to 3.01) L, p
      < 0.001. Fat mass increased from 22.7 +/- 11.1 to 23.7 +/- 11.3 kg, p = 0.007).
      The change in ECW/total body water (TBW) was associated with age (beta 0.065, p <
      0.001), increasing comorbidity (beta 1.107, p = 0.005), faster peritoneal protein
      transport (beta 1.84, p < 0.04), and negatively with serum albumin (beta -0.208,
      p < 0.001), and residual renal function (beta -0.725, p = 0.026). Patients who
      had an increase in ECW/TBW had higher C-reactive protein (CRP) both before
      starting (16.8 +/- 24.1 vs 7.7 +/- 18.9 mg/L), and when established on PD (15.0
      +/- 31.8 vs 4.6 +/- 5.1 mg/L), p < 0.05. Rather than a reduction in ECW hydration
      status, overhydration increased after starting PD. This was greater for older
      more comorbid patients and those with an inflammatory milieu and lower residual
      renal function. These factors should be considered when deciding upon initial PD
      prescriptions to limit ECW overhydration before information on peritoneal
      membrane function becomes available.

PMID- 28512163
TI  - Retroperitoneal Laparoscopic Radical Nephrectomy Allows Continuation of
      Peritoneal Dialysis in Patients with End-Stage Renal Disease.
AB  - Patient outcomes for retroperitoneal laparoscopic radical nephrectomy (RLRN) in
      adults on peritoneal dialysis (PD) have not been described in the literature.
      This is the first series on the successful application of RLRN for renal cell
      carcinoma (RCC) among adults with end-stage renal disease (ESRD) on PD. In our
      series of 5 patients, all were able to promptly resume PD, no wound complications
      were noted at postoperative visits, and no evidence of recurrence was identified
      on surveillance imaging at follow-up. We propose that RLRN should be considered
      in PD patients as it allows immediate reinstitution of PD and prevents the
      morbidity and complications associated with interim hemodialysis.

PMID- 28512165
TI  - The Use of the Galactomannan Test to Diagnose Peritoneal Dialysis-Associated
      Penicillium Peritonitis.

PMID- 28512164
TI  - Time to Positivity of Bacteria Cultures in Peritoneal Dialysis Fluid: Evaluation
      of Different Laboratory Techniques.
AB  - Patients with chronic kidney disease on peritoneal dialysis (PD) are susceptible
      to infections, with peritonitis being the primary cause of dropout. Peritoneal
      fluid culture is one of the essential elements for proper diagnosis and
      peritonitis treatment. The aim of this study was to compare the time required to
      obtain a positive culture using different laboratory methods. An in vitro cross
      sectional study was conducted comparing different techniques for preparation and
      culture of bacteria in peritoneal fluid. The research was carried out with 21
      sterile dialysis bags and 21 PD bags containing peritoneal fluid drained from
      patients without peritonitis. Fluids from the 42 PD bags were contaminated by
      injecting a coagulase-negative Staphylococcus suspension and then prepared for
      culture using 4 distinct techniques: A - direct culture; B - post-centrifugation
      culture; C - direct culture after 4 h sedimentation; and D - culture after 4 h
      sedimentation and centrifugation. This was followed by seeding. In the 21
      contaminated sterile bags, mean times to obtain a positive culture with
      techniques D (19.6 h +/- 2.6) and C (19.1 h +/- 2.3) were longer than with
      technique A (15.8 h +/- 3.0; p < 0.01), but not statistically different from
      group B (19.0 h +/- 3.2). The same occurred in the 21 bags drained from patients,
      with mean times for techniques D (14.0 h +/- 1.9) and C (14.5 h +/- 1.7) being
      longer than technique A (12.22 h +/- 1.94; p < 0.05) but not statistically
      different from technique B (13.2 h +/- 1.3). The sedimentation and centrifugation
      steps seem to be unnecessary and may delay antibiotic sensitivity test results by
      approximately 8 hours.

PMID- 28512166
TI  - A Case of Peritoneal Dialysis-Associated Peritonitis Caused by Agromyces
      mediolanus.

PMID- 28512167
TI  - Candida parapsilosis Peritonitis-Macroscopic and Microscopic Appearances.

PMID- 28512168
TI  - Hydrocele Caused by Peritoneal Fluid Leakage Through Inguinal Canal.

PMID- 28512169
TI  - Eosinophilia in Peritoneal Effluent Due To a Levonorgestrel-Releasing
      Intrauterine System in a Woman on Peritoneal Dialysis.

PMID- 28512170
TI  - Deconstruction of Interhospital Transfer Workflow in Large Vessel Occlusion: Real
      World Data in the Thrombectomy Era.
AB  - BACKGROUND AND PURPOSE: Interhospital transfer is a critical component in the
      treatment of acute anterior circulation large vessel occlusive stroke transferred
      for mechanical thrombectomy. Real-world data for benchmarking and theoretical
      modeling are limited. We sought to characterize transfer workflow from primary
      stroke center (PSC) to comprehensive stroke center after the publication of
      positive thrombectomy trials. METHODS: Consecutive patients transferred from 3
      high-volume PSCs to a single comprehensive stroke center between January 2015 and
      August 2016 were included in a retrospective study. Factors associated with key
      time metrics were analyzed with emphasis on PSC intrahospital workflow. RESULTS:
      Sixty-seven patients were identified. Median age was 74 years (interquartile
      range [IQR], 63.5-78) and National Institutes of Health Stroke Scale 17 (IQR, 12
      21). Median transfer time measured by PSC-door-to-comprehensive stroke center
      door was 128 minutes (IQR, 107-164), of which 82.8% was spent at PSCs (door-in
      door-out [DIDO]; 106 minutes; IQR, 86-143). The lengthiest component of DIDO was
      computed-tomography-to-retrieval-request (median 59.5 minutes; IQR, 44-83). The
      37.3% had DIDO exceeding 120 minutes. DIDO times differed significantly between
      PSCs (P=0.01). In multivariate analyses, rerecruiting the initial ambulance crew
      for transfer (P<0.01) and presentation during working hours (P=0.04) were
      associated with shorter DIDO times. CONCLUSIONS: In a metropolitan hub-and-spoke
      network, PSC-door-to-comprehensive stroke center-door and DIDO times are long
      even in high-volume PSCs. Improving PSC workflow represents a major opportunity
      to expedite mechanical thrombectomy and improve patient outcomes.

PMID- 28512171
TI  - Effect of message congruency on attention and recall in pictorial health warning
      labels.
AB  - OBJECTIVE: The nine pictorial health warning labels (PWLs) proposed by the US
      Food and Drug Administration vary in format and feature of visual and textual
      information. Congruency is the degree to which visual and textual features
      reflect a common theme. This characteristic can affect attention and recall of
      label content. This study investigates the effect of congruency in PWLs on
      smoker's attention and recall of label content. METHODS: 120 daily smokers were
      randomly assigned to view either congruent or incongruent PWLs, while having
      their eye movements recorded. Participants were asked to recall label content
      immediately after exposure and 5 days later. RESULTS: Overall, the image was
      viewed more and recalled better than the text. Smokers in the incongruent
      condition spent more time focusing on the text than smokers in the congruent
      condition (p=0.03), but dwell time of the image did not differ. Despite lower
      dwell time on the text, smokers in the congruent condition were more likely to
      correctly recall it on day 1 (p=0.02) and the risk message of the PWLs on both
      day 1 (p=0.01) and day 5 (p=0.006) than smokers in the incongruent condition.
      CONCLUSIONS: This study identifies an important design feature of PWLs and
      demonstrates objective differences in how smokers process PWLs. Our results
      suggest that message congruency between visual and textual information is
      beneficial to recall of label content. Moreover, images captured and held
      smokers' attention better than the text.

PMID- 28512172
TI  - In Vivo Hemin Conditioning Targets the Vascular and Immunologic Compartments and
      Restrains Prostate Tumor Development.
AB  - Purpose: Conditioning strategies constitute a relatively unexplored and exciting
      opportunity to shape tumor fate by targeting the tumor microenvironment. In this
      study, we assessed how hemin, a pharmacologic inducer of heme oxygenase-1 (HO-1),
      has an impact on prostate cancer development in an in vivo conditioning
      model.Experimental Design: The stroma of C57BL/6 mice was conditioned by
      subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge.
      Complementary in vitro and in vivo assays were performed to evaluate hemin effect
      on both angiogenesis and the immune response. To gain clinical insight, we used
      prostate cancer patient-derived samples in our studies to assess the expression
      of HO-1 and other relevant genes.Results: Conditioning resulted in increased
      tumor latency and decreased initial growth rate. Histologic analysis of tumors
      grown in conditioned mice revealed impaired vascularization. Hemin-treated human
      umbilical vein endothelial cells (HUVEC) exhibited decreased tubulogenesis in
      vitro only in the presence of TRAMP-C1-conditioned media. Subcutaneous hemin
      conditioning hindered tumor-associated neovascularization in an in vivo Matrigel
      plug assay. In addition, hemin boosted CD8+ T-cell proliferation and
      degranulation in vitro and antigen-specific cytotoxicity in vivo A significant
      systemic increase in CD8+ T-cell frequency was observed in preconditioned tumor
      bearing mice. Tumors from hemin-conditioned mice showed reduced expression of
      galectin-1 (Gal-1), key modulator of tumor angiogenesis and immunity, evidencing
      persistent remodeling of the microenvironment. We also found a subset of prostate
      cancer patient-derived xenografts and prostate cancer patient samples with mild
      HO-1 and low Gal-1 expression levels.Conclusions: These results highlight a novel
      function of a human-used drug as a means of boosting the antitumor response. Clin
      Cancer Res; 23(17); 5135-48. (c)2017 AACR.

PMID- 28512173
TI  - Clinical Utility of Risk Models to Refer Patients with Adnexal Masses to
      Specialized Oncology Care: Multicenter External Validation Using Decision Curve
      Analysis.
AB  - Purpose: To evaluate the utility of preoperative diagnostic models for ovarian
      cancer based on ultrasound and/or biomarkers for referring patients to
      specialized oncology care. The investigated models were RMI, ROMA, and 3 models
      from the International Ovarian Tumor Analysis (IOTA) group [LR2, ADNEX, and the
      Simple Rules risk score (SRRisk)].Experimental Design: A secondary analysis of
      prospectively collected data from 2 cross-sectional cohort studies was performed
      to externally validate diagnostic models. A total of 2,763 patients (2,403 in
      dataset 1 and 360 in dataset 2) from 18 centers (11 oncology centers and 7
      nononcology hospitals) in 6 countries participated. Excised tissue was
      histologically classified as benign or malignant. The clinical utility of the
      preoperative diagnostic models was assessed with net benefit (NB) at a range of
      risk thresholds (5%-50% risk of malignancy) to refer patients to specialized
      oncology care. We visualized results with decision curves and generated bootstrap
      confidence intervals.Results: The prevalence of malignancy was 41% in dataset 1
      and 40% in dataset 2. For thresholds up to 10% to 15%, RMI and ROMA had a lower
      NB than referring all patients. SRRisks and ADNEX demonstrated the highest NB. At
      a threshold of 20%, the NBs of ADNEX, SRrisks, and RMI were 0.348, 0.350, and
      0.270, respectively. Results by menopausal status and type of center (oncology
      vs. nononcology) were similar.Conclusions: All tested IOTA methods, especially
      ADNEX and SRRisks, are clinically more useful than RMI and ROMA to select
      patients with adnexal masses for specialized oncology care. Clin Cancer Res;
      23(17); 5082-90. (c)2017 AACR.

PMID- 28512175
TI  - 2015/2016 Quality Risk Management Benchmarking Survey.
AB  - This paper investigates the concept of quality risk management (QRM) maturity as
      it applies to the pharmaceutical and biopharmaceutical industries, using the
      results and analysis from a QRM benchmarking survey conducted in 2015 and 2016.
      QRM maturity can be defined as the effectiveness and efficiency of a quality risk
      management program, moving beyond "check-the-box" compliance with guidelines such
      as ICH Q9 Quality Risk Management, to explore the value QRM brings to business
      and quality operations. While significant progress has been made towards full
      adoption of QRM principles and practices across industry, the full benefits of
      QRM have not yet been fully realized. The results of the QRM Benchmarking Survey
      indicate that the pharmaceutical and biopharmaceutical industries are
      approximately halfway along the journey towards full QRM maturity.LAY ABSTRACT:
      The management of risks associated with medicinal product quality and patient
      safety are an important focus for the pharmaceutical and biopharmaceutical
      industries. These risks are identified, analyzed, and controlled through a
      defined process called quality risk management (QRM), which seeks to protect the
      patient from potential quality-related risks. This paper summarizes the outcomes
      of a comprehensive survey of industry practitioners performed in 2015 and 2016
      that aimed to benchmark the level of maturity with regard to the application of
      QRM. The survey results and subsequent analysis revealed that the pharmaceutical
      and biopharmaceutical industries have made significant progress in the management
      of quality risks over the last ten years, and they are roughly halfway towards
      reaching full maturity of QRM.

PMID- 28512176
TI  - Extractables Screening of Polypropylene Resins Used in Pharmaceutical Packaging
      for Safety Hazards.
AB  - Pharmaceutical products are packaged in containers so that they can be
      manufactured, distributed, and used. Because extractables from such containers
      are precursors of leachable impurities in the product, extractables represent
      potential hazards to user safety. Polypropylene resins are frequently used as
      materials of construction for packaging of liquid parenteral drug products. Thus,
      extractables profiling of polypropylene resins may be an effective means of
      hazard identification associated with the resin's safe use. Twenty-one
      polypropylene resins were extracted using aqueous and organic extraction
      solvents, and the resulting extracts were screened for extractables using
      appropriate general chemistry, chromatographic, and spectroscopic methodologies.
      The resulting extractables profiles were toxicologically reviewed by a defined
      process to identify potential hazards given a specified therapeutic application
      involving long-term use of a large-volume aqueous parenteral drug product. The
      organic extractables profiles of individual polypropylene resins were variable in
      terms of the individual extractable identified and their extracted levels,
      consistent with high variability in polypropylene resin formulations and
      pharmaceutical product manufacturing. However, the profiles were similar in terms
      of the groups of extractables measured. Thus, for example, all the resins had
      extractables associated with antioxidants, as all the resins contained
      antioxidants but the specific extractables for a given resin depended on the
      specific antioxidants present in that resin. Few of the targeted extractable
      elements were present in the extracts at measurable levels, although most resins
      had measurable levels of extracted aluminum, silicon, and alkali and alkaline
      earths. A worst-case extractables profile (all the extractables measured in
      individual resins at their highest levels) was toxicologically reviewed
      considering an aqueous large-volume parenteral drug product. This review
      established certain extractables as potential hazards whose actual toxicological
      safety risk assessment would require more rigorous data and a more rigorous
      process than those used for hazard identification.LAY ABSTRACT: Packages used to
      contain aqueous parenteral drug products may be made of polypropylene. During
      storage, extractables from the polypropylene may leach out of the container and
      accumulate in the drug product, where they could affect product quality and/or
      safety. In this study, 21 polypropylene resins were characterized with respect to
      their organic and elemental extractables profiles. A worst-case extractables
      profile (highest level of all the extractables identified) was toxicologically
      assessed to establish potentially hazardous extractables. Certain extractables
      were established as potential hazards whose actual toxicological safety risk
      assessment would require more rigorous data and a more rigorous process than
      those used for hazard identification.

PMID- 28512174
TI  - Dynamic Changes in PD-L1 Expression and Immune Infiltrates Early During Treatment
      Predict Response to PD-1 Blockade in Melanoma.
AB  - Purpose: Disruption of PD-L1/cytotoxic T-cell PD-1 signaling by immune checkpoint
      inhibitors improves survival in cancer patients. This study sought to identify
      changes in tumoral PD-L1 expression and tumor-associated immune cell flux with
      anti-PD-1 therapies in patients with melanoma, particularly early during
      treatment, and correlate them with treatment response.Experimental Design: Forty
      six tumor biopsies from 23 patients with unresectable AJCC stage III/IV melanoma
      receiving pembrolizumab/nivolumab were analyzed. Biopsies were collected prior to
      (PRE, n = 21), within 2 months of commencing treatment (EDT, n = 20) and on
      disease progression after previous response (PROG, n = 5). Thirteen patients
      responded (defined as CR, PR, or durable SD by RECIST/irRC criteria), and 10 did
      not respond.Results: PRE intratumoral and peritumoral PD-1+ T-cell densities were
      sevenfold (P = 0.006) and fivefold higher (P = 0.011), respectively, in
      responders compared with nonresponders and correlated with degree of radiologic
      tumor response (r = -0.729, P = 0.001 and r = -0.725, P = 0.001, respectively).
      PRE PD-L1 expression on tumor and macrophages was not significantly different
      between the patient groups, but tumoral PD-L1 and macrophage PD-L1 expression was
      higher in the EDT of responders versus nonresponders (P = 0.025 and P = 0.033).
      Responder EDT biopsies (compared with PRE) also showed significant increases in
      intratumoral CD8+ lymphocytes (P = 0.046) and intratumoral CD68+ macrophages (P =
      0.046).Conclusions: Higher PRE PD-1+ T cells in responders suggest active
      suppression of an engaged immune system that is disinhibited by anti-PD-1
      therapies. Furthermore, immunoprofiling of EDT biopsies for increased PD-L1
      expression and immune cell infiltration showed greater predictive utility than
      PRE biopsies and may allow better selection of patients most likely to benefit
      from anti-PD-1 therapies and warrants further evaluation. Clin Cancer Res;
      23(17); 5024-33. (c)2017 AACR.

PMID- 28512177
TI  - Evaluation of Novel Process Indicators for Rapid Monitoring of Hydrogen Peroxide
      Decontamination Processes.
AB  - Geobacillus stearothermophilus spores on stainless steel discs are routinely used
      as biological indicators for the validation of hydrogen peroxide bio
      decontamination processes. Given ongoing concerns about the reliability and
      response time of biological indicators, we explored the potential for an enzyme
      based approach to decontamination process evaluation. Thermostable adenylate
      kinase enzyme was coated onto a solid support and exposed to hydrogen peroxide
      vapour, in parallel with standard commercial 6-log biological indicators, during
      a series of vapour-phase hydrogen peroxide cycles in a flexible film isolator.
      The exposed biological indicators were enumerated to define the degree of kill at
      different time intervals and the results compared to the thermostable adenylate
      kinase values, as determined by measuring adenosine triphosphate produced by
      residual active enzyme. Both biological indicators and the thermostable adenylate
      kinase indicators exhibited a biphasic inactivation profile during the process.
      There was significant variance between individual cycles, with some cycles
      showing complete inactivation of the biological indicators to the limit of
      detection of the assay, within 6 min, whereas biological indicators in some
      cycles were inactivated at a time greater than 12 min. The log-kill of the
      biological indicators at intermediate time points were plotted and compared to
      the fully quantifiable measurements derived from the thermostable adenylate
      kinase indicators at the same time points. The results demonstrated very similar
      inactivation profiles for the enzyme and for the biological indicators, thus it
      was possible to define a relationship between relative light units measurement
      and biological indicator kill. This indicates that it is possible to use
      thermostable adenylate kinase measurement as a direct measure of vapour-phase
      hydrogen peroxide bio-decontamination performance, expressed in terms of log
      reduction. Because thermostable adenylate kinase measurement can be achieved
      within a few minutes of vapour-phase hydrogen peroxide cycle completion, compared
      with a minimum of 7 days for the evaluation of biological indicator growth, this
      offers a potentially valuable tool for rapid vapour-phase hydrogen peroxide bio
      decontamination cycle development and subsequent re-qualification.LAY ABSTRACT:
      Pharmaceutical product manufacture is performed in controlled cleanroom and
      closed chamber environments (isolators) to reduce the risk of contamination.
      These environments undergo regular decontamination to control microbial
      contamination levels, using a range of methods, one of which is to vaporize
      hydrogen peroxide (a chemical disinfectant) into a gas or an aerosol and disperse
      it throughout the environment, killing any microorganisms present. Biological
      indicators, which consist of a small steel coupon carrying a population of
      bacterial spores that are more resistant to hydrogen peroxide than are most
      microorganisms, are placed within the environment, and then tested for growth
      following treatment to ensure the process was effective. Confirmation of
      growth/no growth (and therefore hydrogen peroxide cycle efficacy) can take up to
      7 days, which significantly increases time and cost of developing and confirming
      cycle efficacy. This study tests whether a new technology which uses a robust
      enzyme, thermostable adenylate kinase, could be used to predict biological
      indicator growth. The study shows this method can be used to confirm hydrogen
      peroxide cycle efficacy, by predicting whether the BI is killed at a specific
      time point or not and results are obtained in a few minutes rather than 7 days.
      This potentially offers significant time and cost benefits.

PMID- 28512178
TI  - Particulate Generation Mechanisms during Bulk Filling and Mitigation via New
      Glass Vial.
AB  - Contamination with foreign particulate matter continues to be a leading cause of
      parenteral drug recalls, despite extensive control and inspection during
      manufacturing. Glass is a significant source of particulate matter contamination;
      however, the mechanism, source, and quantification have not been extensively
      analyzed. Quantification of particulate matter generation with lab simulations
      suggests that glass-to-glass contact on the filling line produces large
      quantities of glass particles of various sizes. A new strengthened glass vial
      with a low coefficient of friction surface is proposed to address this root cause
      of glass particle generation. Lab simulations and two line trials using this new
      vial demonstrated a substantial reduction of glass particulate generation, of
      resulting product contamination, as well as of the frequency of required filling
      line interventions. These results suggest that substantial reductions in
      particulate matter contamination of all types, glass and non-glass, can be
      achieved through the use of a new glass vial designed to effectively eliminate a
      root cause of glass particle generation.LAY ABSTRACT: Contamination with foreign
      particulate contamination continues to be a leading cause of injectable drug
      recalls, despite extensive control and inspection during manufacturing. Glass
      particles are one of the most common types of particulate identified; however,
      the generation mechanism has not been extensively studied. Lab simulations
      suggest that routine glass-to-glass contact of vials during the filling process
      results in large quantities of glass particulate. A new, strengthened glass vial
      with a low coefficient of friction surface is proposed to address this mechanism.
      Lab simulations and multiple filling line trials demonstrated a substantial
      reduction of glass particulate matter generation and product contamination with
      use of the new vial. These results suggest that this new vial reduces
      contamination risk by eliminating a root cause of glass particulate generation.

PMID- 28512181
TI  - Inner Workings: In search for "magic" nuclei, theory catches up to experiments.

PMID- 28512183
TI  - Measles outbreak in Somali American community follows anti-vaccine talks.

PMID- 28512179
TI  - Cooperative Regulatory Functions of miR858 and MYB83 during Cyst Nematode
      Parasitism.
AB  - MicroRNAs (miRNAs) recently have been established as key regulators of
      transcriptome reprogramming that define cell function and identity. Nevertheless,
      the molecular functions of the greatest number of miRNA genes remain to be
      determined. Here, we report cooperative regulatory functions of miR858 and its
      MYB83 transcription factor target gene in transcriptome reprogramming during
      Heterodera cyst nematode parasitism of Arabidopsis (Arabidopsis thaliana). Gene
      expression analyses and promoter-GUS fusion assays documented a role of miR858 in
      posttranscriptional regulation of MYB83 in the Heterodera schachtii-induced
      feeding sites, the syncytia. Constitutive overexpression of miR858 interfered
      with H. schachtii parasitism of Arabidopsis, leading to reduced susceptibility,
      while reduced miR858 abundance enhanced plant susceptibility. Similarly, MYB83
      expression increases were conducive to nematode infection because overexpression
      of a noncleavable coding sequence of MYB83 significantly increased plant
      susceptibility, whereas a myb83 mutation rendered the plants less susceptible. In
      addition, RNA-seq analysis revealed that genes involved in hormone signaling
      pathways, defense response, glucosinolate biosynthesis, cell wall modification,
      sugar transport, and transcriptional control are the key etiological factors by
      which MYB83 facilitates nematode parasitism of Arabidopsis. Furthermore, we
      discovered that miR858-mediated silencing of MYB83 is tightly regulated through a
      feedback loop that might contribute to fine-tuning the expression of more than a
      thousand of MYB83-regulated genes in the H. schachtii-induced syncytium.
      Together, our results suggest a role of the miR858-MYB83 regulatory system in
      finely balancing gene expression patterns during H. schachtii parasitism of
      Arabidopsis to ensure optimal cellular function.

PMID- 28512184
TI  - Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in
      Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial).
AB  - BACKGROUND: It is currently unknown whether intensive blood pressure (BP)
      lowering beyond that recommended would lead to more lowering of the risk of left
      ventricular hypertrophy (LVH) in patients with hypertension and whether reducing
      the risk of LVH explains the reported cardiovascular disease (CVD) benefits of
      intensive BP lowering in this population. METHODS: This analysis included 8164
      participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension
      but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure
      Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP
      <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg).
      Progression and regression of LVH as defined by Cornell voltage criteria derived
      from standard 12-lead ECGs recorded at baseline and biannually were compared
      between treatment arms during a median follow-up of 3.81 years. The effect of
      intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a
      composite of myocardial infarction, acute coronary syndrome, stroke, heart
      failure, and CVD death) was compared before and after adjustment for LVH as a
      time-varying covariate. RESULTS: Among SPRINT participants without baseline LVH
      (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower
      risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68).
      Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those
      assigned to the intensive (versus standard) BP lowering were 66% more likely to
      regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31
      2.11). Adjustment for LVH as a time-varying covariate did not substantially
      attenuate the effect of intensive BP therapy on CVD events (hazard ratio of
      intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64
      0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment
      for LVH as a time-varying covariate, respectively). CONCLUSIONS: Among patients
      with hypertension but no diabetes mellitus, intensive BP lowering (target
      systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP
      <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH
      and higher rates of regression of LVH in those with existing LVH. This favorable
      effect on LVH did not explain most of the reduction in CVD events associated with
      intensive BP lowering in the SPRINT trial. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

PMID- 28512186
TI  - Building Ultra-High-Density Linkage Maps Based on Efficient Filtering of
      Trustable Markers.
AB  - The study is focused on addressing the problem of building genetic maps in the
      presence of ~103-104 of markers per chromosome. We consider a spectrum of
      situations with intrachromosomal heterogeneity of recombination rate, different
      level of genotyping errors, and missing data. In the ideal scenario of the
      absence of errors and missing data, the majority of markers should appear as
      groups of cosegregating markers ("twins") representing no challenge for map
      construction. The central aspect of the proposed approach is to take into account
      the structure of the marker space, where each twin group (TG) and singleton
      markers are represented as points of this space. The confounding effect of
      genotyping errors and missing data leads to reduction of TG size, but upon a low
      level of these effects surviving TGs can still be used as a source of reliable
      skeletal markers. Increase in the level of confounding effects results in a
      considerable decrease in the number or even disappearance of usable TGs and,
      correspondingly, of skeletal markers. Here, we show that the paucity of
      informative markers can be compensated by detecting kernels of markers in the
      marker space using a clustering procedure, and demonstrate the utility of this
      approach for high-density genetic map construction on simulated and
      experimentally obtained genotyping datasets.

PMID- 28512185
TI  - Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in
      the Drosophila melanogaster Wing Imaginal Disc.
AB  - Regeneration is a complex process that requires an organism to recognize and
      repair tissue damage, as well as grow and pattern new tissue. Here, we describe a
      genetic screen to identify novel regulators of regeneration. We ablated the
      Drosophila melanogaster larval wing primordium by inducing apoptosis in a
      spatially and temporally controlled manner and allowed the tissue to regenerate
      and repattern. To identify genes that regulate regeneration, we carried out a
      dominant-modifier screen by assessing the amount and quality of regeneration in
      adult wings heterozygous for isogenic deficiencies. We have identified 31 regions
      on the right arm of the third chromosome that modify the regenerative response.
      Interestingly, we observed several distinct phenotypes: mutants that regenerated
      poorly, mutants that regenerated faster or better than wild-type, and mutants
      that regenerated imperfectly and had patterning defects. We mapped one deficiency
      region to cap-n-collar (cnc), the Drosophila Nrf2 ortholog, which is required for
      regeneration. Cnc regulates reactive oxygen species levels in the regenerating
      epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth,
      debris localization, and pupariation timing. Here, we present the results of our
      screen and propose a model wherein Cnc regulates regeneration by maintaining an
      optimal level of reactive oxygen species to promote JNK signaling.

PMID- 28512188
TI  - The functional movement test 9+ is a poor screening test for lower extremity
      injuries in professional male football players: a 2-year prospective cohort
      study.
AB  - BACKGROUND: The 9+ screening battery test consists of 11 tests to assess
      limitations in functional movement. AIM: To examine the association of the 9+
      with lower extremity injuries and to identify a cut-off point to predict injury
      risk. METHODS: Professional male football players in Qatar from 14 teams
      completed the 9+ at the beginning of the 2013/2014 and 2014/2015 seasons. Time
      loss injuries and exposure in training and matches were registered prospectively
      by club medical staff during these seasons. Univariate and multivariate Cox
      regression analyses were used to calculate HR and 95% CI. Receiver operating
      characteristic (ROC) curves were calculated to determine sensitivity and
      specificity and identify the optimal cut-off point for risk assessment. RESULTS:
      362 players completed the 9+ and had injury and exposure registration. There were
      526 injuries among 203 players (56.1%) during the two seasons; injuries to the
      thigh were the most frequent. There was no association between 9+ total score and
      the risk of lower extremity injuries (HR 1.02, 95% CI 0.99 to 1.05, p=0.13), even
      after adjusting for other risk factors in a multivariate analysis (HR 1.01, 95%
      CI 0.98 to 1.04, p=0.37). ROC curve analysis revealed an area under the curve of
      0.48, and there was no cut-off point that distinguished injured from non-injured
      players. CONCLUSION: The 9+ was not associated with lower extremity injury, and
      it was no better than chance for distinguishing between injured and uninjured
      players. Therefore, the 9+ test cannot be recommended as an injury prediction
      tool in this population.

PMID- 28512187
TI  - Neutral Competition for Drosophila Follicle and Cyst Stem Cell Niches Requires
      Vesicle Trafficking Genes.
AB  - The process of selecting for cellular fitness through competition plays a
      critical role in both development and disease. The germarium, a structure at the
      tip of the ovariole of a Drosophila ovary, contains two follicle stem cells
      (FSCs) that undergo neutral competition for the stem cell niche. Using the FSCs
      as a model, we performed a genetic screen through a collection of 126 mutants in
      essential genes on the X chromosome to identify candidates that increase or
      decrease competition for the FSC niche. We identified ~55 and 6% of the mutations
      screened as putative FSC hypo- or hyper-competitors, respectively. We found that
      a large majority of mutations in vesicle trafficking genes (11 out of the 13 in
      the collection of mutants) are candidate hypo-competition alleles, and we
      confirmed the hypo-competition phenotype for four of these alleles. We also show
      that Sec16 and another COPII vesicle trafficking component, Sar1, are required
      for follicle cell differentiation. Lastly, we demonstrate that, although some
      components of vesicle trafficking are also required for neutral competition in
      the cyst stem cells of the testis, there are important tissue-specific
      differences. Our results demonstrate a critical role for vesicle trafficking in
      stem cell niche competition and differentiation, and we identify a number of
      putative candidates for further exploration.

PMID- 28512189
TI  - When is a study result important for athletes, clinicians and team coaches/staff?

PMID- 28512191
TI  - MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting
      MAML3 and WHSC1 in gastric cancer.
AB  - MicroRNAs have emerged as essential regulators of various cellular processes. We
      identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC)
      metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and
      overexpression of miR-2392 significantly inhibited GC invasion and metastasis in
      vitro and in vivo We identified MAML3 and WHSC1 as novel targets of miR-2392, and
      knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR
      2392 in GC cells. These effects were clinically relevant, as low miR-2392
      expression was correlated with high MAML3 and WHSC1 expression and poor survival
      in patients with GC. Furthermore, forced expression of miR-2392 substantially
      suppressed Slug and Twist1, transcriptional repressors of E-cadherin, by
      targeting MAML3 and WHSC1, respectively, resulting in inhibition of the
      epithelial-mesenchymal transition. These findings indicate that the miR-2392
      MAML3/WHSC1-Slug/Twist1 regulatory axis plays a critical role in GC metastasis.
      Restoration of miR-2392 may be a therapeutic approach for blocking GC metastasis.
      Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F.,
      Zhao, X., Nie, Y., Fan, D. MiR-2392 suppresses metastasis and epithelial
      mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer.

PMID- 28512190
TI  - Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease
      in adults.
AB  - Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare
      histiocytic disorders induced by somatic mutation of MAPK pathway genes.
      BRAFV600E mutation is the most common mutation in both conditions and also occurs
      in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult
      LCH or ECD arises from hematopoietic stem cells (HSCs), nor which potential blood
      borne precursors lead to the formation of histiocytic lesions. In this study,
      BRAFV600E allele-specific polymerase chain reaction was used to map the
      neoplastic clone in 20 adults with LCH, ECD, and HCL. BRAFV600E was tracked to
      classical monocytes, nonclassical monocytes, and CD1c+ myeloid dendritic cells
      (DCs) in the blood, and mutations were observed in HSCs and myeloid progenitors
      in the bone marrow of 4 patients. The pattern of involvement of peripheral blood
      myeloid cells was indistinguishable between LCH and ECD, although the histiocytic
      disorders were distinct to HCL. As reported in children, detection of BRAFV600E
      in peripheral blood of adults was a marker of active multisystem LCH. The healthy
      counterparts of myeloid cells affected by BRAF mutation had a range of
      differentiation potentials depending on exogenous signals. CD1c+ DCs acquired
      high langerin and CD1a with granulocyte-macrophage colony-stimulating factor and
      transforming growth factor beta alone, whereas CD14+ classical monocytes required
      additional notch ligation. Both classical and nonclassical monocytes, but not
      CD1c+ DCs, made foamy macrophages easily in vitro with macrophage colony
      stimulating factor and human serum. These studies are consistent with a
      hematopoietic origin and >1 immediate cellular precursor in both LCH and ECD.

PMID- 28512192
TI  - Human mismatch repair system balances mutation rates between strands by removing
      more mismatches from the lagging strand.
AB  - Mismatch repair (MMR) is one of the main systems maintaining fidelity of
      replication. Differences in correction of errors produced during replication of
      the leading and the lagging DNA strands were reported in yeast and in human
      cancers, but the causes of these differences remain unclear. Here, we analyze
      data on human cancers with somatic mutations in two of the major DNA polymerases,
      delta and epsilon, that replicate the genome. We show that these cancers
      demonstrate a substantial asymmetry of the mutations between the leading and the
      lagging strands. The direction of this asymmetry is the opposite between cancers
      with mutated polymerases delta and epsilon, consistent with the role of these
      polymerases in replication of the lagging and the leading strands in human cells,
      respectively. Moreover, the direction of strand asymmetry observed in cancers
      with mutated polymerase delta is similar to that observed in MMR-deficient
      cancers. Together, these data indicate that polymerase delta (possibly together
      with polymerase alpha) contributes more mismatches during replication than its
      leading-strand counterpart, polymerase epsilon; that most of these mismatches are
      repaired by the MMR system; and that MMR repairs about three times more
      mismatches produced in cells during lagging strand replication compared with the
      leading strand.

PMID- 28512195
TI  - An interview with Eric Wieschaus.
AB  - Eric Wieschaus is a HHMI Investigator, and the Squibb Professor in Molecular
      Biology at Princeton University and the Lewis-Sigler Institute for Integrative
      Genomics. In 1995, he was awarded the Nobel Prize jointly with Edward Lewis and
      Christiane Nusslein-Volhard for discoveries about the genetic control of
      Drosophila embryogenesis. We caught up with Eric at the joint meeting of the
      German and Japanese Societies of Developmental Biologists held in Kiel in March
      2017, and discussed his career, his thoughts on the field and the impact the
      Nobel award had on his life.

PMID- 28512193
TI  - DNA replication timing during development anticipates transcriptional programs
      and parallels enhancer activation.
AB  - In dividing cells, DNA replication occurs in a precise order, but many questions
      remain regarding the mechanisms of replication timing establishment and
      regulation. We now have generated genome-wide, high-resolution replication timing
      maps throughout zebrafish development. Unexpectedly, in the rapid cell cycles
      preceding the midblastula transition, a defined timing program was present that
      predicted the initial wave of zygotic transcription. Replication timing was
      thereafter progressively and continuously remodeled across the majority of the
      genome, and epigenetic changes involved in enhancer activation frequently
      paralleled developmental changes in replication timing. The long arm of
      Chromosome 4 underwent a dramatic developmentally regulated switch to late
      replication during gastrulation, reminiscent of mammalian X Chromosome
      inactivation. This study reveals that replication timing is dynamic and tightly
      linked to epigenetic and transcriptional changes throughout early zebrafish
      development. These data provide insight into the regulation and functions of
      replication timing and will enable further mechanistic studies.

PMID- 28512196
TI  - The developmental biology of genetic Notch disorders.
AB  - Notch signaling regulates a vast array of crucial developmental processes. It is
      therefore not surprising that mutations in genes encoding Notch receptors or
      ligands lead to a variety of congenital disorders in humans. For example, loss of
      function of Notch results in Adams-Oliver syndrome, Alagille syndrome,
      spondylocostal dysostosis and congenital heart disorders, while Notch gain of
      function results in Hajdu-Cheney syndrome, serpentine fibula polycystic kidney
      syndrome, infantile myofibromatosis and lateral meningocele syndrome.
      Furthermore, structure-abrogating mutations in NOTCH3 result in CADASIL. Here, we
      discuss these human congenital disorders in the context of known roles for Notch
      signaling during development. Drawing on recent analyses by the exome aggregation
      consortium (EXAC) and on recent studies of Notch signaling in model organisms, we
      further highlight additional Notch receptors or ligands that are likely to be
      involved in human genetic diseases.

PMID- 28512194
TI  - Ancient antagonism between CELF and RBFOX families tunes mRNA splicing outcomes.
AB  - Over 95% of human multi-exon genes undergo alternative splicing, a process
      important in normal development and often dysregulated in disease. We sought to
      analyze the global splicing regulatory network of CELF2 in human T cells, a well
      studied splicing regulator critical to T cell development and function. By
      integrating high-throughput sequencing data for binding and splicing
      quantification with sequence features and probabilistic splicing code models, we
      find evidence of splicing antagonism between CELF2 and the RBFOX family of
      splicing factors. We validate this functional antagonism through knockdown and
      overexpression experiments in human cells and find CELF2 represses RBFOX2 mRNA
      and protein levels. Because both families of proteins have been implicated in the
      development and maintenance of neuronal, muscle, and heart tissues, we analyzed
      publicly available data in these systems. Our analysis suggests global,
      antagonistic coregulation of splicing by the CELF and RBFOX proteins in mouse
      muscle and heart in several physiologically relevant targets, including proteins
      involved in calcium signaling and members of the MEF2 family of transcription
      factors. Importantly, a number of these coregulated events are aberrantly spliced
      in mouse models and human patients with diseases that affect these tissues,
      including heart failure, diabetes, or myotonic dystrophy. Finally, analysis of
      exons regulated by ancient CELF family homologs in chicken, Drosophila, and
      Caenorhabditis elegans suggests this antagonism is conserved throughout
      evolution.

PMID- 28512200
TI  - A new model for lineage segregation.

PMID- 28512197
TI  - Interstitial fluid osmolarity modulates the action of differential tissue surface
      tension in progenitor cell segregation during gastrulation.
AB  - The segregation of different cell types into distinct tissues is a fundamental
      process in metazoan development. Differences in cell adhesion and cortex tension
      are commonly thought to drive cell sorting by regulating tissue surface tension
      (TST). However, the role that differential TST plays in cell segregation within
      the developing embryo is as yet unclear. Here, we have analyzed the role of
      differential TST for germ layer progenitor cell segregation during zebrafish
      gastrulation. Contrary to previous observations that differential TST drives germ
      layer progenitor cell segregation in vitro, we show that germ layers display
      indistinguishable TST within the gastrulating embryo, arguing against
      differential TST driving germ layer progenitor cell segregation in vivo We
      further show that the osmolarity of the interstitial fluid (IF) is an important
      factor that influences germ layer TST in vivo, and that lower osmolarity of the
      IF compared with standard cell culture medium can explain why germ layers display
      differential TST in culture but not in vivo Finally, we show that directed
      migration of mesendoderm progenitors is required for germ layer progenitor cell
      segregation and germ layer formation.

PMID- 28512198
TI  - Novel role of Rac-Mid1 signaling in medial cerebellar development.
AB  - Rac signaling impacts a relatively large number of downstream targets; however,
      few studies have established an association between Rac pathways and pathological
      conditions. In the present study, we generated mice with double knockout of Rac1
      and Rac3 (Atoh1-Cre;Rac1flox/flox;Rac3-/- ) in cerebellar granule neurons (CGNs).
      We observed impaired tangential migration at E16.5, as well as numerous apoptotic
      CGNs at the deepest layer of the external granule layer (EGL) in the medial
      cerebellum of Atoh1-Cre;Rac1flox/flox;Rac3-/- mice at P8. Atoh1
      Cre;Rac1flox/flox;Rac3-/- CGNs differentiated normally until expression of
      p27kip1 and NeuN in the deep EGL at P5. Primary CGNs and cerebellar microexplants
      from Atoh1-Cre;Rac1flox/flox;Rac3-/- mice exhibited impaired neuritogenesis,
      which was more apparent in Map2-positive dendrites. Such findings suggest that
      impaired tangential migration and final differentiation of CGNs have resulted in
      decreased cerebellum size and agenesis of the medial internal granule layer,
      respectively. Furthermore, Rac depleted/deleted cells exhibited decreased levels
      of Mid1 and impaired mTORC1 signaling. Mid1 depletion in CGNs produced mild
      impairments in neuritogenesis and reductions in mTORC1 signaling. Thus, a novel
      Rac-signaling pathway (Rac1-Mid1-mTORC1) may be involved in medial cerebellar
      development.

PMID- 28512199
TI  - Dominant-negative Sox18 function inhibits dermal papilla maturation and
      differentiation in all murine hair types.
AB  - SOX family proteins SOX2 and SOX18 have been reported as being essential in
      determining hair follicle type; however, the role they play during development
      remains unclear. Here, we demonstrate that Sox18 regulates the normal
      differentiation of the dermal papilla of all hair types. In guard (primary) hair
      dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2
      expression at E14.5, which allowed fate tracing of primary DC cells until birth.
      Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at
      E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum)
      did not prevent DC formation in any hair type. However, it affected dermal
      papilla differentiation, restricting hair formation especially in secondary and
      tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or
      dermal papilla spheres from inducing hair in regeneration assays. Microarray
      expression studies identified WNT5A and TNC as potential downstream effectors of
      SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts
      as a mesenchymal molecular switch necessary for the formation and function of the
      dermal papilla in all hair types.

PMID- 28512202
TI  - Heat shock protein regulates human hepatocyte differentiation.

PMID- 28512201
TI  - Exciting input for inhibitory neurons.

PMID- 28512203
TI  - The mechanism of activation of IRAK1 and IRAK4 by interleukin-1 and Toll-like
      receptor agonists.
AB  - We have developed the first assays that measure the protein kinase activities of
      interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 reliably in human
      cell extracts, by employing Pellino1 as a substrate in conjunction with specific
      pharmacological inhibitors of IRAK1 and IRAK4. We exploited these assays to show
      that IRAK4 was constitutively active and that its intrinsic activity towards
      Pellino1 was not increased significantly by stimulation with interleukin-1 (IL-1)
      in IL-1R-expressing HEK293 cells, Pam3CSK4-stimulated human THP1 monocytes or
      primary human macrophages. Our results, in conjunction with those of other
      investigators, suggest that the IL-1-stimulated trans-autophosphorylation of
      IRAK4 is initiated by the myeloid differentiation primary response gene 88
      induced dimerization of IRAK4 and is not caused by an increase in the intrinsic
      catalytic activity of IRAK4. In contrast with IRAK4, we found that IRAK1 was
      inactive in unstimulated cells and converted into an active protein kinase in
      response to IL-1 or Pam3CSK4 in human cells. Surprisingly, the IL-1-stimulated
      activation of IRAK1 was not affected by pharmacological inhibition of IRAK4 and
      not reversed by dephosphorylation and/or deubiquitylation, suggesting that IRAK1
      catalytic activity is not triggered by a covalent modification but by an
      allosteric mechanism induced by its interaction with IRAK4.

PMID- 28512206
TI  - Genetic testing and reproductive choice in neurological disorders.
AB  - Genetic testing is increasingly important for investigating suspected inherited
      neurological conditions. A genetic diagnosis can have a huge impact on patients
      and also their families. It is important for neurologists to appreciate the
      presymptomatic and prenatal testing options available to patients and their at
      risk relatives once a genetic disorder is diagnosed. Asymptomatic family members
      can experience considerable psychological distress from the knowledge that they
      might have inherited a neurodegenerative condition. They may also be concerned
      about the risk of their children inheriting the condition. Information on
      reproductive options can provide hope and reassurance. This paper reviews the
      principles of genetic testing in neurological practice, and how they can be
      applied in prenatal and preimplantation genetic diagnosis. We explain the basis
      for direct and exclusion testing, use case examples to illustrate the process by
      which families are counselled and discuss the ethical implications of
      reproductive technologies.

PMID- 28512204
TI  - The human RNA-binding protein RBFA promotes the maturation of the mitochondrial
      ribosome.
AB  - Accurate assembly and maturation of human mitochondrial ribosomes is essential
      for synthesis of the 13 polypeptides encoded by the mitochondrial genome. This
      process requires the correct integration of 80 proteins, 1 mt (mitochondrial)
      tRNA and 2 mt-rRNA species, the latter being post-transcriptionally modified at
      many sites. Here, we report that human ribosome-binding factor A (RBFA) is a
      mitochondrial RNA-binding protein that exerts crucial roles in mitoribosome
      biogenesis. Unlike its bacterial orthologue, RBFA associates mainly with helices
      44 and 45 of the 12S rRNA in the mitoribosomal small subunit to promote
      dimethylation of two highly conserved consecutive adenines. Characterization of
      RBFA-depleted cells indicates that this dimethylation is not a prerequisite for
      assembly of the small ribosomal subunit. However, the RBFA-facilitated
      modification is necessary for completing mt-rRNA maturation and regulating
      association of the small and large subunits to form a functional monosome
      implicating RBFA in the quality control of mitoribosome formation.

PMID- 28512207
TI  - 'Organic' and 'non-organic': a tale of two turnips.

PMID- 28512205
TI  - Phorbol-12-myristate-13-acetate-mediated stabilization of leukemia inhibitory
      factor (lif) mRNA: involvement of Nucleolin and PCBP1.
AB  - Leukemia inhibitory factor (LIF) is a potent pleiotropic cytokine involved in
      diverse biological activities, thereby requiring precise spatial and temporal
      control of its expression. The present study reveals that enhanced expression of
      LIF in response to PMA (phorbol-12-myristate-13-acetate) in human histiocytic
      lymphoma cell line U937 largely happens through stabilization of its mRNA.
      Functional characterization of the long 3'-untranslated region of human lif mRNA
      revealed several conserved sequences with conventional cis-acting elements. A 216
      nucleotide containing proximal cis-element with two AUUUA pentamers and four poly
      rC sequences demonstrated significant mRNA destabilizing potential, which, on
      treatment with PMA, showed stabilizing activity. Affinity chromatography followed
      by western blot and RNA co-immunoprecipitation of PMA-treated U937 extract
      identified Nucleolin and PCBP1 as two protein trans-factors interacting with lif
      mRNA, specifically to the proximal non-conventional AU-rich region. PMA induced
      nucleo-cytoplasmic translocation of both Nucleolin and PCBP1. RNA-dependent in
      vivo co-association of both these proteins with lif mRNA was demonstrated by
      decreased co-precipitation in the presence of RNase. Ectopic overexpression of
      Nucleolin showed stabilization of both intrinsic lif mRNA and gfp reporter,
      whereas knockdown of Nucleolin and PCBP1 demonstrated a significant decrease in
      both lif mRNA and protein levels. Collectively, this report establishes the
      stabilization of lif mRNA by PMA, mediated by the interactions of two RNA-binding
      proteins, Nucleolin and PCBP1 with a proximal cis-element.

PMID- 28512208
TI  - Chorioretinitis: a potential clue to the early diagnosis of subacute sclerosing
      panencephalitis.
AB  - We describe a 36-year-old man with subacute sclerosing panencephalitis (SSPE)
      presenting with chorioretinitis two years before onset of other neurological
      features. He had neither myoclonus nor the typical EEG features of SSPE. The
      diagnosis was confirmed in the appropriate clinical setting by detecting elevated
      measles antibody titres in cerebrospinal fluid and serum. Clinicians should
      consider SSPE among the differential diagnoses in chorioretinitis. This is
      particularly so if there is macular or perimacular involvement with concurrent
      involvement of the optic nerve in young patients, even without other
      characteristic neurological symptoms.

PMID- 28512209
TI  - Venous hypertensive encephalopathy secondary to venous sinus thrombosis and dural
      arteriovenous fistula.
AB  - A 52-year-old man with a history of factor V Leiden thrombophilia, persistent
      headaches and papilloedema presented with worsening vision and confusion. MRI and
      MR angiography of the brain at the time of this presentation showed findings
      concerning for transverse sinus thrombosis and an associated dural arteriovenous
      fistula. Dural venous sinus thrombosis can lead to the formation of a dural
      arteriovenous fistula, which must be considered in the differential diagnosis for
      intracranial hypertension in patients with thrombophilia.

PMID- 28512210
TI  - Margaret McCartney: The NHS needs big, firm IT pants.

PMID- 28512211
TI  - Correction for Bernard et al., "Splicing Factor Spf30 Assists Exosome-Mediated
      Gene Silencing in Fission Yeast".

PMID- 28512212
TI  - Correction for Khalimonchuk et al., "Formation of the Redox Cofactor Centers
      during Cox1 Maturation in Yeast Cytochrome Oxidase".

PMID- 28512213
TI  - Retraction for Roy et al., "DDB2, an Essential Mediator of Premature Senescence".

PMID- 28512214
TI  - Correction for Munoz-Galvan et al., "Distinct Roles of Mus81, Yen1, Slx1-Slx4,
      and Rad1 Nucleases in the Repair of Replication-Born Double-Strand Breaks by
      Sister Chromatid Exchange".

PMID- 28512216
TI  - Setting the (Scientific) Record Straight: Molecular and Cellular Biology Responds
      to Postpublication Review.

PMID- 28512217
TI  - Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like
      symptoms in zebrafish.
AB  - RAD51 is an indispensable homologous recombination protein, necessary for strand
      invasion and crossing over. It has recently been designated as a Fanconi anemia
      (FA) gene, following the discovery of two patients carrying dominant-negative
      mutations. FA is a hereditary DNA-repair disorder characterized by various
      congenital abnormalities, progressive bone marrow failure, and cancer
      predisposition. In this report, we describe a viable vertebrate model of RAD51
      loss. Zebrafish rad51 loss-of-function mutants developed key features of FA,
      including hypocellular kidney marrow, sensitivity to cross-linking agents, and
      decreased size. We show that some of these symptoms stem from both decreased
      proliferation and increased apoptosis of embryonic hematopoietic stem and
      progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects
      seen in the single mutants, but led to tumor development. We further demonstrate
      that prolonged inflammatory stress can exacerbate the hematological impairment,
      leading to an additional decrease in kidney marrow cell numbers. These findings
      strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence
      for the notion that aberrant p53 signaling during embryogenesis leads to the
      hematological defects seen later in life in FA. Further research on this
      zebrafish FA model will lead to a deeper understanding of the molecular basis of
      bone marrow failure in FA and the cellular role of RAD51.

PMID- 28512219
TI  - Energetic cost of building a virus.
AB  - Viruses are incapable of autonomous energy production. Although many experimental
      studies make it clear that viruses are parasitic entities that hijack the
      molecular resources of the host, a detailed estimate for the energetic cost of
      viral synthesis is largely lacking. To quantify the energetic cost of viruses to
      their hosts, we enumerated the costs associated with two very distinct but
      representative DNA and RNA viruses, namely, T4 and influenza. We found that, for
      these viruses, translation of viral proteins is the most energetically expensive
      process. Interestingly, the costs of building a T4 phage and a single influenza
      virus are nearly the same. Due to influenza's higher burst size, however, the
      overall cost of a T4 phage infection is only 2-3% of the cost of an influenza
      infection. The costs of these infections relative to their host's estimated
      energy budget during the infection reveal that a T4 infection consumes about a
      third of its host's energy budget, whereas an influenza infection consumes only ~
      1%. Building on our estimates for T4, we show how the energetic costs of double
      stranded DNA phages scale with the capsid size, revealing that the dominant cost
      of building a virus can switch from translation to genome replication above a
      critical size. Last, using our predictions for the energetic cost of viruses, we
      provide estimates for the strengths of selection and genetic drift acting on
      newly incorporated genetic elements in viral genomes, under conditions of energy
      limitation.

PMID- 28512221
TI  - Shear bands as manifestation of a criticality in yielding amorphous solids.
AB  - Amorphous solids increase their stress as a function of an applied strain until a
      mechanical yield point whereupon the stress cannot increase anymore, afterward
      exhibiting a steady state with a constant mean stress. In stress-controlled
      experiments, the system simply breaks when pushed beyond this mean stress. The
      ubiquity of this phenomenon over a huge variety of amorphous solids calls for a
      generic theory that is free of microscopic details. Here, we offer such a theory:
      The mechanical yield is a thermodynamic phase transition, where yield occurs as a
      spinodal phenomenon. At the spinodal point, there exists a divergent correlation
      length that is associated with the system-spanning instabilities (also known as
      shear bands), which are typical to the mechanical yield. The theory, the order
      parameter used, and the correlation functions that exhibit the divergent
      correlation length are universal in nature and can be applied to any amorphous
      solids that undergo mechanical yield.

PMID- 28512218
TI  - Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP*NPLOC4*UFD1L is
      enhanced by a mutation that causes multisystem proteinopathy.
AB  - p97 is a "segregase" that plays a key role in numerous ubiquitin (Ub)-dependent
      pathways such as ER-associated degradation. It has been hypothesized that p97
      extracts proteins from membranes or macromolecular complexes to enable their
      proteasomal degradation; however, the complex nature of p97 substrates has made
      it difficult to directly observe the fundamental basis for this activity. To
      address this issue, we developed a soluble p97 substrate-Ub-GFP modified with K48
      linked ubiquitin chains-for in vitro p97 activity assays. We demonstrate that WT
      p97 can unfold proteins and that this activity is dependent on the p97 adaptor
      NPLOC4-UFD1L, ATP hydrolysis, and substrate ubiquitination, with branched chains
      providing maximal stimulation. Furthermore, we show that a p97 mutant that causes
      inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia in
      humans unfolds substrate faster, suggesting that excess activity may underlie
      pathogenesis. This work overcomes a significant barrier in the study of p97 and
      will allow the future dissection of p97 mechanism at a level of detail previously
      unattainable.

PMID- 28512220
TI  - Increasing intracellular magnesium levels with the 31-amino acid MgtS protein.
AB  - Synthesis of the 31-amino acid, inner membrane protein MgtS (formerly denoted
      YneM) is induced by very low Mg2+ in a PhoPQ-dependent manner in Escherichia coli
      Here we report that MgtS acts to increase intracellular Mg2+ levels and maintain
      cell integrity upon Mg2+ depletion. Upon development of a functional tagged
      derivative of MgtS, we found that MgtS interacts with MgtA to increase the levels
      of this P-type ATPase Mg2+ transporter under Mg2+-limiting conditions.
      Correspondingly, the effects of MgtS upon Mg2+ limitation are lost in a ?mgtA
      mutant, and MgtA overexpression can suppress the ?mgtS phenotype. MgtS
      stabilization of MgtA provides an additional layer of regulation of this tightly
      controlled Mg2+ transporter and adds to the list of small proteins that regulate
      inner membrane transporters.

PMID- 28512222
TI  - Looplessness in networks is linked to trophic coherence.
AB  - Many natural, complex systems are remarkably stable thanks to an absence of
      feedback acting on their elements. When described as networks these exhibit few
      or no cycles, and associated matrices have small leading eigenvalues. It has been
      suggested that this architecture can confer advantages to the system as a whole,
      such as "qualitative stability," but this observation does not in itself explain
      how a loopless structure might arise. We show here that the number of feedback
      loops in a network, as well as the eigenvalues of associated matrices, is
      determined by a structural property called trophic coherence, a measure of how
      neatly nodes fall into distinct levels. Our theory correctly classifies a variety
      of networks-including those derived from genes, metabolites, species, neurons,
      words, computers, and trading nations-into two distinct regimes of high and low
      feedback and provides a null model to gauge the significance of related
      magnitudes. Because trophic coherence suppresses feedback, whereas an absence of
      feedback alone does not lead to coherence, our work suggests that the reasons for
      "looplessness" in nature should be sought in coherence-inducing mechanisms.

PMID- 28512223
TI  - Kinematics of the lever arm swing in myosin VI.
AB  - Myosin VI (MVI) is the only known member of the myosin superfamily that, upon
      dimerization, walks processively toward the pointed end of the actin filament.
      The leading head of the dimer directs the trailing head forward with a power
      stroke, a conformational change of the motor domain exaggerated by the lever arm.
      Using a unique coarse-grained model for the power stroke of a single MVI, we
      provide the molecular basis for its motility. We show that the power stroke
      occurs in two major steps. First, the motor domain attains the poststroke
      conformation without directing the lever arm forward; and second, the lever arm
      reaches the poststroke orientation by undergoing a rotational diffusion. From the
      analysis of the trajectories, we discover that the potential that directs the
      rotating lever arm toward the poststroke conformation is almost flat, implying
      that the lever arm rotation is mostly uncoupled from the motor domain. Because a
      backward load comparable to the largest interhead tension in a MVI dimer prevents
      the rotation of the lever arm, our model suggests that the leading-head lever arm
      of a MVI dimer is uncoupled, in accord with the inference drawn from polarized
      total internal reflection fluorescence (polTIRF) experiments. Without any
      adjustable parameter, our simulations lead to quantitative agreement with polTIRF
      experiments, which validates the structural insights. Finally, in addition to
      making testable predictions, we also discuss the implications of our model in
      explaining the broad step-size distribution of the MVI stepping pattern.

PMID- 28512224
TI  - The general form of Hamilton's rule makes no predictions and cannot be tested
      empirically.
AB  - Hamilton's rule asserts that a trait is favored by natural selection if the
      benefit to others, [Formula: see text], multiplied by relatedness, [Formula: see
      text], exceeds the cost to self, [Formula: see text] Specifically, Hamilton's
      rule states that the change in average trait value in a population is
      proportional to [Formula: see text] This rule is commonly believed to be a
      natural law making important predictions in biology, and its influence has spread
      from evolutionary biology to other fields including the social sciences. Whereas
      many feel that Hamilton's rule provides valuable intuition, there is disagreement
      even among experts as to how the quantities [Formula: see text], [Formula: see
      text], and [Formula: see text] should be defined for a given system. Here, we
      investigate a widely endorsed formulation of Hamilton's rule, which is said to be
      as general as natural selection itself. We show that, in this formulation,
      Hamilton's rule does not make predictions and cannot be tested empirically. It
      turns out that the parameters [Formula: see text] and [Formula: see text] depend
      on the change in average trait value and therefore cannot predict that change. In
      this formulation, which has been called "exact and general" by its proponents,
      Hamilton's rule can "predict" only the data that have already been given.

PMID- 28512225
TI  - High Arctic Holocene temperature record from the Agassiz ice cap and Greenland
      ice sheet evolution.
AB  - We present a revised and extended high Arctic air temperature reconstruction from
      a single proxy that spans the past ~12,000 y (up to 2009 CE). Our reconstruction
      from the Agassiz ice cap (Ellesmere Island, Canada) indicates an earlier and
      warmer Holocene thermal maximum with early Holocene temperatures that are 4-5 
      degrees C warmer compared with a previous reconstruction, and regularly exceed
      contemporary values for a period of ~3,000 y. Our results show that air
      temperatures in this region are now at their warmest in the past 6,800-7,800 y,
      and that the recent rate of temperature change is unprecedented over the entire
      Holocene. The warmer early Holocene inferred from the Agassiz ice core leads to
      an estimated ~1 km of ice thinning in northwest Greenland during the early
      Holocene using the Camp Century ice core. Ice modeling results show that this
      large thinning is consistent with our air temperature reconstruction. The
      modeling results also demonstrate the broader significance of the enhanced
      warming, with a retreat of the northern ice margin behind its present position in
      the mid Holocene and a ~25% increase in total Greenland ice sheet mass loss (~1.4
      m sea-level equivalent) during the last deglaciation, both of which have
      implications for interpreting geodetic measurements of land uplift and gravity
      changes in northern Greenland.

PMID- 28512226
TI  - Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally
      boosting direct-acting antiviral-based treatments.

PMID- 28512227
TI  - Reply to Candel et al.: Evidence for evolutionary conservation of folding
      kinetics in the thioredoxin protein family.

PMID- 28512228
TI  - Fast folding and slow unfolding of a resurrected Precambrian protein.

PMID- 28512229
TI  - Inhibitors of hepatitis C virus entry may be potent ingredients of optimal drug
      combinations.

PMID- 28512231
TI  - Survey on antimicrobial prescribing patterns in small animal veterinary practice
      in Emilia Romagna, Italy.
AB  - This investigation provides for the first time a general view of the prescribing
      patterns ofantimicrobials in small animal practice in Emilia Romagna, Italy. In
      the context of a projecton antimicrobial resistance managed by the Regional
      Veterinary Service, veterinary clinicianswere invited to voluntarily complete an
      online questionnaire. This was designed to gatherinformation on antimicrobial
      prescribing practices and biosecurity measures and tounderstand the perception of
      the issue specific to this region of Italy. In total, 266questionnaires correctly
      completed were collected. Although clinicians seemed to followdifferent
      approaches when using antimicrobials, the data analysis revealed a
      generalawareness on resistance. Penicillins were the most commonly prescribed
      class, followed by(fluoro)quinolones and cephalosporins. Among those who use
      laboratory testing more orless frequently (microbiological analysis and
      susceptibility testing) to support theirprescribing habits, only 7 per cent make
      a habit of always waiting for the results beforestarting the treatment. Seventy
      eight per cent of the respondents declared the use ofantimicrobials licensed for
      human beings. Biosecurity measures were carefully taken intoaccount by the
      majority of the veterinarians. The results identified the antimicrobial
      classesthat are commonly prescribed and highlighted that perioperative hygiene
      measures and theuse of laboratory diagnosis are critical aspects that need to be
      emphasised in drawing upguidelines on the prudent use of these drugs in pets.

PMID- 28512232
TI  - Loop-mediated isothermal amplification for extended spectrum beta-lactamase gene
      detection in poultry carcase.

PMID- 28512233
TI  - Identification, assessment and management of new and re-emerging animal-related
      risks: UK perspective.
AB  - Veterinary surveillance programmes aim to reduce the burden to the public,
      livestock andwider society posed by animal-related 'risks' (referred to as
      'threats' later in the paper inline with a definition used by the European Food
      Safety Authority) including the reemergenceof diseases believed absent or
      eradicated. To achieve this, it is important to havea systematic approach to
      identifying and dealing with such threats rapidly and effectively.This paper
      describes the transparent, systematic and auditable process used for
      identifying,assessing, escalating and prioritising new and re-emerging animal
      related threats in the UK.This has been achieved through the establishment of a
      Veterinary Risk Group in late 2009.

PMID- 28512230
TI  - Differential Proteomic Analysis of Gender-dependent Hepatic Tumorigenesis in
      Hras12V Transgenic Mice.
AB  - Male prevalence is an outstanding characteristic of hepatocellular carcinoma
      (HCC), and the underlying mechanisms for this have remained largely unknown. In
      the present study, Hras12V transgenic mice, in which hepatocyte-specific
      expression of the ras oncogene induces male-biased hepatic tumorigenesis, were
      studied, and altered proteins were detected by two-dimensional fluorescence
      difference gel electrophoresis (2D-DIGE). Protein samples from hepatic tumor
      tissues (T) and peritumor tissues (P) of transgenic males and females and the
      corresponding normal liver tissues (Wt) of nontransgenic males and females were
      subjected to pairwise comparisons based on proteomic analysis. Among 2381
      autodetected protein spots, more than 1600 were differentially expressed based on
      a pairwise comparison (|ratio| > = 1.5, p < = 0.05). Of these, 180 spots were
      randomly selected for matrix-assisted laser desorption ionization tandem time-of
      flight mass spectrometry (MALDI-TOF/TOF MS) identification; finally, 89 distinct
      proteins were obtained. Among these 89 proteins, 7 and 50 proteins were further
      validated by Western blotting and literature investigation, respectively.
      Intriguingly, compared with Wt, the altered proteins were relatively concentrated
      in T in transgenic females but in P in transgenic males. Consistently, the levels
      of p-ERK and p-mTOR were significantly higher in the T of females compared with
      that of males. The pathway enrichment assay showed that 5 pathways in males but
      only 1 in females were significantly altered in terms of the upregulated proteins
      in T compared with Wt. These data indicate that female hepatocytes are disturbed
      by oncogenes with great difficulty, whereas male hepatocytes readily do so. In
      addition, 33 proteins were gender-dependently altered in hepatic tumorigenesis.
      Moreover, 4% DNA packaging and 4% homeostasis-related functional proteins were
      found in females but not in males, and more nucleus proteins were found in
      females (8%) than in males (3%). In conclusion, the proteomic data and
      comparative analysis presented here offer crucial clues for elucidating the
      mechanisms that underlie the male prevalence in HCC.

PMID- 28512234
TI  - A guide for targeted SUMO removal.
AB  - SUMO homeostasis is important for many cellular processes. In the current issue
      of Genes & Development, Liang and colleagues (pp. 802-815) demonstrate how a
      desumoylation enzyme is targeted to the nucleolus for removing SUMO from specific
      substrates and how curtailing sumoylation levels can regulate transcription in
      this nuclear compartment.

PMID- 28512235
TI  - Identifying the niche controlling melanocyte differentiation.
AB  - Melanocytes present in hair follicles are responsible for their pigmentation.
      Melanocyte differentiation and hair pigmentation depend on the stem cell factor
      (SCF)/c-Kit signaling pathway, but the niche that regulates melanocyte
      differentiation is not well characterized. In this issue of Genes & Development,
      Liao and colleagues (pp. 744-756) identify Krox20+-derived cells of the hair
      shaft as the niche and the essential source of SCF required for melanocyte
      maturation. This study delineates the niche factors regulating melanocyte
      differentiation and hair pigmentation and opens up new avenues to further
      characterize the cross-talk between the hair follicle and melanocytes that
      controls melanocyte maintenance and differentiation.

PMID- 28512238
TI  - Corrigendum: Evolution of a transcriptional regulator from a transmembrane
      nucleoporin.

PMID- 28512239
TI  - Erratum: BRaf signaling principles unveiled by large-scale human mutation
      analysis with a rapid lentivirus-based gene replacement method.

PMID- 28512237
TI  - Regulation of DNA demethylation by the XPC DNA repair complex in somatic and
      pluripotent stem cells.
AB  - Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent
      state during cellular reprogramming requires DNA methylation to silence somatic
      gene expression and dynamic DNA demethylation to activate pluripotency gene
      transcription. The removal of methylated cytosines requires the base excision
      repair enzyme TDG, but the mechanism by which TDG-dependent DNA demethylation
      occurs in a rapid and site-specific manner remains unclear. Here we show that the
      XPC DNA repair complex is a potent accelerator of global and locus-specific DNA
      demethylation in somatic and pluripotent stem cells. XPC cooperates with TDG
      genome-wide to stimulate the turnover of essential intermediates by overcoming
      slow TDG-abasic product dissociation during active DNA demethylation. We further
      establish that DNA demethylation induced by XPC expression in somatic cells
      overcomes an early epigenetic barrier in cellular reprogramming and facilitates
      the generation of more robust induced pluripotent stem cells, characterized by
      enhanced pluripotency-associated gene expression and self-renewal capacity. Taken
      together with our previous studies establishing the XPC complex as a
      transcriptional coactivator, our findings underscore two distinct but
      complementary mechanisms by which XPC influences gene regulation by coordinating
      efficient TDG-mediated DNA demethylation along with active transcription during
      somatic cell reprogramming.

PMID- 28512241
TI  - Assessment of Breast Cancer Risk Factors Reveals Subtype Heterogeneity.
AB  - Subtype heterogeneity for breast cancer risk factors has been suspected,
      potentially reflecting etiologic differences and implicating risk prediction.
      However, reports are conflicting regarding the presence of heterogeneity for many
      exposures. To examine subtype heterogeneity across known breast cancer risk
      factors, we conducted a case-control analysis of 2,632 breast cancers and 15,945
      controls in Sweden. Molecular subtype was predicted from pathology record-derived
      IHC markers by a classifier trained on PAM50 subtyping. Multinomial logistic
      regression estimated separate ORs for each subtype by the exposures parity, age
      at first birth, breastfeeding, menarche, hormone replacement therapy use,
      somatotype at age 18, benign breast disease, mammographic density, polygenic risk
      score, family history of breast cancer, and BRCA mutations. We found clear
      subtype heterogeneity for genetic factors and breastfeeding. Polygenic risk score
      was associated with all subtypes except for the basal-like (Pheterogeneity <
      0.0001). "Never breastfeeding" was associated with increased risk of basal-like
      subtype [OR 4.17; 95% confidence interval (CI) 1.89-9.21] compared with both
      nulliparity (reference) and breastfeeding. Breastfeeding was not associated with
      risk of HER2-overexpressing type, but protective for all other subtypes. The
      observed heterogeneity in risk of distinct breast cancer subtypes for germline
      variants supports heterogeneity in etiology and has implications for their use in
      risk prediction. The association between basal-like subtype and breastfeeding
      merits more research into potential causal mechanisms and confounders. Cancer
      Res; 77(13); 3708-17. (c)2017 AACR.

PMID- 28512236
TI  - Focus on cutaneous and uveal melanoma specificities.
AB  - Cutaneous melanoma (CM) and uveal melanoma (UM) derive from cutaneous and uveal
      melanocytes that share the same embryonic origin and display the same cellular
      function. However, the etiopathogenesis and biological behaviors of these
      melanomas are very different. CM and UM display distinct landscapes of genetic
      alterations and show different metastatic routes and tropisms. Hence, therapeutic
      improvements achieved in the last few years for the treatment of CM have failed
      to ameliorate the clinical outcomes of patients with UM. The scope of this review
      is to discuss the differences in tumorigenic processes (etiologic factors and
      genetic alterations) and tumor biology (gene expression and signaling pathways)
      between CM and UM. We develop hypotheses to explain these differences, which
      might provide important clues for research avenues and the identification of
      actionable vulnerabilities suitable for the development of new therapeutic
      strategies for metastatic UM.

PMID- 28512240
TI  - STING Activation Reverses Lymphoma-Mediated Resistance to Antibody Immunotherapy.
AB  - Tumors routinely attract and co-opt macrophages to promote their growth,
      angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb
      therapies. Here we report that the tumor microenvironment creates an
      immunosuppressive signature on tumor-associated macrophages (TAM), which favors
      expression of inhibitory rather than activating Fcgamma receptors (FcgammaR),
      thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR
      and STING agonists (a) for their ability to reprogram macrophages to a state
      optimal for mAb immunotherapy. Both STINGa and TLRa induced cytokine release,
      modulated FcgammaR expression, and augmented mAb-mediated tumor cell phagocytosis
      in vitro However, only STINGa reversed the suppressive FcgammaR profile in vivo,
      providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma.
      Potent adjuvants like STINGa, which can improve FcgammaR activatory:inhibitory
      (A:I) ratios on TAM, are appealing candidates to reprogram TAM and curb tumor
      mediated immunosuppression, thereby empowering mAb efficacy. Cancer Res; 77(13);
      3619-31. (c)2017 AACR.

PMID- 28512242
TI  - A Systematic Analysis of Oncogenic Gene Fusions in Primary Colon Cancer.
AB  - Genomic rearrangements that give rise to oncogenic gene fusions can offer
      actionable targets for cancer therapy. Here we present a systematic analysis of
      oncogenic gene fusions among a clinically well-characterized, prospectively
      collected set of 278 primary colon cancers spanning diverse tumor stages and
      clinical outcomes. Gene fusions and somatic genetic variations were identified in
      fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene
      detection pipeline, and GATK RNA-seq variant calling. We considered gene fusions
      to be pathogenically relevant when recurrent, producing divergent gene expression
      (outlier analysis), or as functionally important (e.g., kinase fusions). Overall,
      2.5% of all specimens were defined as harboring a relevant gene fusion (kinase
      fusions 1.8%). Novel configurations of BRAF, NTRK3, and RET gene fusions
      resulting from chromosomal translocations were identified. An R-spondin fusion
      was found in only one tumor (0.35%), much less than an earlier reported frequency
      of 10% in colorectal cancers. We also found a novel fusion involving USP9X-ERAS
      formed by chromothripsis and leading to high expression of ERAS, a constitutively
      active RAS protein normally expressed only in embryonic stem cells. This USP9X
      ERAS fusion appeared highly oncogenic on the basis of its ability to activate AKT
      signaling. Oncogenic fusions were identified only in lymph node-negative tumors
      that lacked BRAF or KRAS mutations. In summary, we identified several novel
      oncogenic gene fusions in colorectal cancer that may drive malignant development
      and offer new targets for personalized therapy. Cancer Res; 77(14); 3814-22.
      (c)2017 AACR.

PMID- 28512243
TI  - Plk1 Phosphorylation of Mre11 Antagonizes the DNA Damage Response.
AB  - The mitotic kinase Plk1 contributes to the DNA damage response (DDR) by targeting
      multiple factors downstream of the core responder kinase ATM/ATR. In this study,
      we show that Polo-like kinase 1 (Plk1) also phosphorylates key factors upstream
      of ATM/ATR and regulates their DDR-related functions. Plk1 phosphorylated Mre11,
      a component of the Mre11/Rad50/Nbs1 (MRN) complex, at serine 649 (S649) during
      DDR. Phosphorylation of Mre11-S649 by Plk1 primed subsequent CK2-mediated
      phosphorylation at Mre11-serine 688 (S688). Phosphorylation of Mre11 at S649/S688
      inhibited loading of the MRN complex to damaged DNA, leading to both premature
      DNA damage checkpoint termination and inhibition of DNA repair. Tumors expressing
      phosphomimetic Mre11 were more sensitive to the PARP inhibitor olaparib, compared
      with those expressing unphosphorylatable Mre11, suggesting that patients with
      elevated Plk1 expression might benefit from olaparib treatment. Cancer Res;
      77(12); 3169-80. (c)2017 AACR.

PMID- 28512244
TI  - Engineering and Functional Characterization of Fusion Genes Identifies Novel
      Oncogenic Drivers of Cancer.
AB  - Oncogenic gene fusions drive many human cancers, but tools to more quickly
      unravel their functional contributions are needed. Here we describe methodology
      permitting fusion gene construction for functional evaluation. Using this
      strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6
      NTRK3, as well as 20 previously uncharacterized fusion genes identified in The
      Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the
      known fusion oncogenes engineered by our construction strategy, we validated five
      novel fusion genes involving MET, NTRK2, and BRAF kinases that exhibited potent
      transforming activity and conferred sensitivity to FDA-approved kinase
      inhibitors. Our fusion construction strategy also enabled domain-function studies
      of BRAF fusion genes. Our results confirmed other reports that the transforming
      activity of BRAF fusions results from truncation-mediated loss of inhibitory
      domains within the N-terminus of the BRAF protein. BRAF mutations residing within
      this inhibitory region may provide a means for BRAF activation in cancer,
      therefore we leveraged the modular design of our fusion gene construction
      methodology to screen N-terminal domain mutations discovered in tumors that are
      wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic
      mutation, F247L, whose expression robustly activated the MAPK pathway and
      sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools
      will facilitate rapid fusion gene construction for subsequent functional
      characterization and translation into personalized treatment strategies. Cancer
      Res; 77(13); 3502-12. (c)2017 AACR.

PMID- 28512245
TI  - Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like
      Tumor Development in Mice.
AB  - Merkel cell carcinoma (MCC) tumor cells express several markers detected in
      normal Merkel cells, a nonproliferative population of neuroendocrine cells that
      arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV)
      DNA and express viral transforming antigens, sT and tLT, but the role of these
      putative oncogenes in MCC development, and this tumor's cell of origin, are
      unknown. Using a panel of preterm transgenic mice, we show that epidermis
      targeted coexpression of sT and the cell fate-determinant atonal bHLH
      transcription factor 1 (ATOH1) leads to development of widespread cellular
      aggregates, with histology and marker expression mimicking that of human
      intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7
      binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV
      tLT did not appreciably alter the phenotype driven by either sT or sT combined
      with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate
      development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12);
      3151-7. (c)2017 AACR.

PMID- 28512246
TI  - Tumor-Associated Macrophages Promote Malignant Progression of Breast Phyllodes
      Tumors by Inducing Myofibroblast Differentiation.
AB  - Myofibroblast differentiation plays an important role in the malignant
      progression of phyllodes tumor, a fast-growing neoplasm derived from periductal
      stromal cells of the breast. Macrophages are frequently found in close proximity
      with myofibroblasts, but it is uncertain whether they are involved in the
      myofibroblast differentiation during phyllodes tumor progression. Here we show
      that increased density of tumor-associated macrophage (TAM) correlates with
      malignant progression of phyllodes tumor. We found that TAMs stimulated
      myofibroblast differentiation and promoted the proliferation and invasion of
      phyllodes tumor cells. Furthermore, we found that levels of the chemokine CCL18
      in TAM was an independent prognostic factor of phyllodes tumor. Mechanistic
      investigations showed that CCL18 promoted expression of alpha-smooth muscle
      actin, a hallmark of myofibroblast, along with the proliferation and invasion of
      phyllodes tumor cells, and that CCL18-driven myofibroblast differentiation was
      mediated by an NF-kappaB/miR-21/PTEN/AKT signaling axis. In murine xenograft
      models of human phyllodes tumor, CCL18 accelerated tumor growth, induced
      myofibroblast differentiation, and promoted metastasis. Taken together, our
      findings indicated that TAM drives myofibroblast differentiation and malignant
      progression of phyllodes tumor through a CCL18-driven signaling cascade amenable
      to antibody disruption. Cancer Res; 77(13); 3605-18. (c)2017 AACR.

PMID- 28512247
TI  - Targetable T-type Calcium Channels Drive Glioblastoma.
AB  - Glioblastoma (GBM) stem-like cells (GSC) promote tumor initiation, progression,
      and therapeutic resistance. Here, we show how GSCs can be targeted by the FDA
      approved drug mibefradil, which inhibits the T-type calcium channel Cav3.2. This
      calcium channel was highly expressed in human GBM specimens and enriched in GSCs.
      Analyses of the The Cancer Genome Atlas and REMBRANDT databases confirmed
      upregulation of Cav3.2 in a subset of tumors and showed that overexpression
      associated with worse prognosis. Mibefradil treatment or RNAi-mediated
      attenuation of Cav3.2 was sufficient to inhibit the growth, survival, and
      stemness of GSCs and also sensitized them to temozolomide chemotherapy. Proteomic
      and transcriptomic analyses revealed that Cav3.2 inhibition altered cancer
      signaling pathways and gene transcription. Cav3.2 inhibition suppressed GSC
      growth in part by inhibiting prosurvival AKT/mTOR pathways and stimulating
      proapoptotic survivin and BAX pathways. Furthermore, Cav3.2 inhibition decreased
      expression of oncogenes (PDGFA, PDGFB, and TGFB1) and increased expression of
      tumor suppressor genes (TNFRSF14 and HSD17B14). Oral administration of mibefradil
      inhibited growth of GSC-derived GBM murine xenografts, prolonged host survival,
      and sensitized tumors to temozolomide treatment. Our results offer a
      comprehensive characterization of Cav3.2 in GBM tumors and GSCs and provide a
      preclinical proof of concept for repurposing mibefradil as a mechanism-based
      treatment strategy for GBM. Cancer Res; 77(13); 3479-90. (c)2017 AACR.

PMID- 28512248
TI  - Androgen Receptor Supports an Anchorage-Independent, Cancer Stem Cell-like
      Population in Triple-Negative Breast Cancer.
AB  - Preclinical and early clinical trials indicate that up to 50% of triple-negative
      breast cancers (TNBC) express androgen receptor (AR) and are potentially
      responsive to antiandrogens. However, the function of AR in TNBC and the
      mechanisms by which AR-targeted therapy reduces tumor burden are largely unknown.
      We hypothesized that AR maintains a cancer stem cell (CSC)-like tumor-initiating
      population and serves as an antiapoptotic factor, facilitating anchorage
      independence and metastasis. AR levels increased in TNBC cells grown in forced
      suspension culture compared with those in attached conditions, and cells that
      expressed AR resisted detachment-induced apoptosis. Culturing TNBC cells in
      suspension increased the CSC-like population, an effect reversed by AR
      inhibition. Pretreatment with enzalutamide (Enza) decreased the tumor-initiating
      capacity of TNBC cells and reduced tumor volume and viability when administered
      simultaneously or subsequent to the chemotherapeutic paclitaxel; simultaneous
      treatment more effectively suppressed tumor recurrence. Overall, our findings
      suggest that AR-targeted therapies may enhance the efficacy of chemotherapy even
      in TNBCs with low AR expression by targeting a CSC-like cell population with
      anchorage independence and invasive potential. Cancer Res; 77(13); 3455-66.
      (c)2017 AACR.

PMID- 28512251
TI  - Inhibition of the Cell Death Pathway in Nonalcoholic Steatohepatitis (NASH)
      Related Hepatocarcinogenesis Is Associated with Histone H4 lysine 16
      Deacetylation.
AB  - Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers, and
      its incidence is steadily increasing worldwide. Recent epidemiologic findings
      have suggested that the increased incidence of HCC is associated with obesity,
      type II diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the
      mechanisms and the molecular pathogenesis of NASH-related HCC are not fully
      understood. To elucidate the underlying mechanisms of the development of NASH
      related HCC, we investigated the hepatic transcriptomic and histone modification
      profiles in Stelic Animal Model mice, the first animal model of NASH-related HCC
      to resemble the disease pathogenesis in humans. The results demonstrate that the
      development of NASH-related HCC is characterized by progressive transcriptomic
      alterations, global loss of histone H4 lysine 20 trimethylation (H4K20me3), and
      global and gene-specific deacetylation of histone H4 lysine 16 (H4K16). Pathway
      analysis of the entire set of differentially expressed genes indicated that the
      inhibition of cell death pathway was the most prominent alteration, and this was
      facilitated by persistent gene-specific histone H4K16 deacetylation.
      Mechanistically, deacetylation of histone H4K16 was associated with
      downregulation of lysine acetyltransferase KAT8, which was driven by
      overexpression of its inhibitor nuclear protein 1 (Nupr1). The results of this
      study identified a reduction of global and gene-specific histone H4K16
      acetylation as a key pathophysiologic mechanism contributing to the development
      of NASH-derived HCC and emphasized the importance of epigenetic alterations as
      diagnostic and therapeutic targets for HCC.Implications: Histone H4K16
      deacetylation induces silencing of genes related to the cell death that occurred
      during the development of NASH-related HCC. Mol Cancer Res; 15(9); 1163-72.
      (c)2017 AACR.

PMID- 28512249
TI  - p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production,
      Maintain Mitochondrial Integrity, and Promote Tumorigenesis.
AB  - p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic
      substrate that accumulates in cells with hyperactive mTORC1, such as kidney cells
      with mutations in the tumor suppressor genes tuberous sclerosis complex (TSC)1 or
      TSC2. Here we report that p62 is a critical mediator of TSC2-driven
      tumorigenesis, as Tsc2+/- and Tsc2f/f Ksp-CreERT2+ mice crossed to p62-/- mice
      were protected from renal tumor development. Metabolic profiling revealed that
      depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate,
      and glutathione (GSH). p62 positively regulated the glutamine transporter Slc1a5
      and increased glutamine uptake in Tsc2-null cells. We also observed p62-dependent
      changes in Gcl, Gsr, Nqo1, and Srxn1, which were decreased by p62 attenuation and
      implicated in GSH production and utilization. p62 attenuation altered
      mitochondrial morphology, reduced mitochondrial membrane polarization and maximal
      respiration, and increased mitochondrial reactive oxygen species and mitophagy
      marker PINK1. These mitochondrial phenotypes were rescued by addition of
      exogenous GSH and overexpression of Sod2, which suppressed indices of
      mitochondrial damage and promoted growth of Tsc2-null cells. Finally, p62
      depletion sensitized Tsc2-null cells to both oxidative stress and direct
      inhibition of GSH biosynthesis by buthionine sulfoximine. Our findings show how
      p62 helps maintain intracellular pools of GSH needed to limit mitochondrial
      dysfunction in tumor cells with elevated mTORC1, highlighting p62 and redox
      homeostasis as nodal vulnerabilities for therapeutic targeting in these tumors.
      Cancer Res; 77(12); 3255-67. (c)2017 AACR.

PMID- 28512252
TI  - Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
AB  - Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular
      profile. Mesenchymal identity in GBM has been associated with a comparatively
      unfavorable prognosis, primarily due to inherent resistance of these tumors to
      current therapies. The identification of molecular determinants of mesenchymal
      transformation could potentially allow for the discovery of new therapeutic
      targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc
      finger transcriptional repressor with a crucial role in brain development and
      neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal
      subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes
      to the aggressive phenotype of glioblastoma through regulation of poor prognosis
      associated signatures. Restitution of ZBTB18 expression reverses the phenotype
      and impairs tumor-forming ability. These results indicate that ZBTB18 functions
      as a tumor suppressor in GBM through the regulation of genes associated with
      phenotypically aggressive properties.Implications: This study characterizes the
      role of the putative tumor suppressor ZBTB18 and its regulation by promoter
      hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the
      mesenchymal subtype of GBM and provides a new mechanistic opportunity to
      specifically target this tumor subclass. Mol Cancer Res; 15(8); 998-1011. (c)2017
      AACR.

PMID- 28512250
TI  - Introduction to the human gut microbiota.
AB  - The human gastrointestinal (GI) tract harbours a complex and dynamic population
      of microorganisms, the gut microbiota, which exert a marked influence on the host
      during homeostasis and disease. Multiple factors contribute to the establishment
      of the human gut microbiota during infancy. Diet is considered as one of the main
      drivers in shaping the gut microbiota across the life time. Intestinal bacteria
      play a crucial role in maintaining immune and metabolic homeostasis and
      protecting against pathogens. Altered gut bacterial composition (dysbiosis) has
      been associated with the pathogenesis of many inflammatory diseases and
      infections. The interpretation of these studies relies on a better understanding
      of inter-individual variations, heterogeneity of bacterial communities along and
      across the GI tract, functional redundancy and the need to distinguish cause from
      effect in states of dysbiosis. This review summarises our current understanding
      of the development and composition of the human GI microbiota, and its impact on
      gut integrity and host health, underlying the need for mechanistic studies
      focusing on host-microbe interactions.

PMID- 28512253
TI  - Infiltrating Myeloid Cells Exert Protumorigenic Actions via Neutrophil Elastase.
AB  - Tissue infiltration and elevated peripheral circulation of granulocytic myeloid
      derived cells is associated with poor outcomes in prostate cancer and other
      malignancies. Although myeloid-derived cells have the ability to suppress T-cell
      function, little is known about the direct impact of these innate cells on
      prostate tumor growth. Here, it is reported that granulocytic myeloid-derived
      suppressor cells (MDSC) are the predominant tumor-infiltrating cells in prostate
      cancer xenografts established in athymic nude mice. MDSCs significantly increased
      in number in the peripheral circulation as a function of xenograft growth and
      were successfully depleted in vivo by Gr-1 antibody treatment. Importantly, MDSC
      depletion significantly decreased xenograft growth. We hypothesized that
      granulocytic MDSCs might exert their protumorigenic actions in part through
      neutrophil elastase (ELANE), a serine protease released upon granulocyte
      activation. Indeed, it was determined that NE is expressed by infiltrating immune
      cells and is enzymatically active in prostate cancer xenografts and in prostate
      tumors of prostate-specific Pten-null mice. Importantly, treatment with
      sivelestat, a small-molecule inhibitor specific for NE, significantly decreased
      xenograft growth, recapitulating the phenotype of Gr-1 MDSC depletion.
      Mechanistically, NE activated MAPK signaling and induced MAPK-dependent
      transcription of the proliferative gene cFOS in prostate cancer cells.
      Functionally, NE stimulated proliferation, migration, and invasion of prostate
      cancer cells in vitro IHC on human prostate cancer clinical biopsies revealed
      coexpression of NE and infiltrating CD33+ MDSCs.Implications: This report
      suggests that MDSCs and NE are physiologically important mediators of prostate
      cancer progression and may serve as potential biomarkers and therapeutic targets.
      Mol Cancer Res; 15(9); 1138-52. (c)2017 AACR.

PMID- 28512255
TI  - Immune consequences of penfluridol treatment associated with inhibition of
      glioblastoma tumor growth.
AB  - Glioblastoma is the most common and lethal brain tumor associated with only 12%
      median survival rate of patients. Despite the development of advanced surgical,
      radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma
      patients is still a challenge. The major contributing factor in glioblastoma
      progression and resistive nature is its ability to evade the immune surveillance.
      Hence, modulating the immune system in glioblastoma tumors could be an important
      strategy for anticancer therapeutics. Penfluridol, an antipsychotic drug has been
      shown to have anti-cancer properties in our recently published studies. The
      present study evaluates the immune response of penfluridol in glioblastoma
      tumors. Our results demonstrated that penfluridol treatment significantly
      suppressed glioblastoma tumor growth. Our current results demonstrated about 72%
      suppression of myeloid derived suppressor cells (MDSCs) with penfluridol
      treatment in mouse bearing U87MG glioblastoma tumors. MDSCs are known to increase
      regulatory T cells (Treg), which are immunosuppressive in nature and suppresses
      M1 macrophages that are tumor suppressive in nature. Our results also showed
      suppression of regulatory T cells as well as elevation of M1 macrophages with
      penfluridol treatment by 58% and 57% respectively. Decrease in CCL4 as well as
      IFNgamma with penfluridol treatment was also observed indicating decrease in
      overall tumor inflammation. This is the first report demonstrating immune
      modulations by penfluridol treatment associated with glioblastoma tumor growth
      suppression prompting further investigation to establish penfluridol as a
      treatment option for glioblastoma patients.

PMID- 28512254
TI  - Catecholamines facilitate VEGF-dependent angiogenesis via beta2-adrenoceptor
      induced Epac1 and PKA activation.
AB  - Chronic stress has been associated with the progression of cancer and antagonists
      for beta-adrenoceptors (betaAR) are regarded as therapeutic option. As they are
      also used to treat hemangiomas as well as retinopathy of prematurity, a role of
      endothelial beta2AR in angiogenesis can be envisioned. We therefore investigated
      the role of beta2AR-induced cAMP formation by analyzing the role of the cAMP
      effector molecules exchange factor directly activated by cAMP 1 (Epac1) and
      protein kinase A (PKA) in endothelial cells (EC). Epac1-deficient mice showed a
      reduced amount of pre-retinal neovascularizations in the model of oxygen-induced
      retinopathy, which is predominantly driven by vascular endothelial growth factor
      (VEGF). siRNA-mediated knockdown of Epac1 in human umbilical vein EC (HUVEC)
      decreased angiogenic sprouting by lowering the expression of the endothelial VEGF
      receptor-2 (VEGFR-2). Conversely, Epac1 activation by beta2AR stimulation or the
      Epac-selective activator cAMP analog 8-p-CPT-2'-O-Me-cAMP (8-pCPT) increased
      VEGFR-2 levels and VEGF-dependent sprouting. Similar to Epac1 knockdown,
      depletion of the monomeric GTPase Rac1 decreased VEGFR-2 expression. As Epac1
      stimulation induces Rac1 activation, Epac1 might regulate VEGFR-2 expression
      through Rac1. In addition, we found that PKA was also involved in the regulation
      of angiogenesis in EC since the adenylyl cyclase (AC) activator forskolin (Fsk),
      but not 8-pCPT, increased sprouting in Epac1-depleted HUVEC and this increase was
      sensitive to a selective synthetic peptide PKA inhibitor. In accordance, beta2AR-
      and AC-activation, but not Epac1 stimulation increased VEGF secretion in
      HUVEC.Our data indicate that high levels of catecholamines, which occur during
      chronic stress, prime the endothelium for angiogenesis through a beta2AR-mediated
      increase in endothelial VEGFR-2 expression and VEGF secretion.

PMID- 28512264
TI  - Gallic acid inhibits the release of ADAMTS4 in nucleus pulposus cells by
      inhibiting p65 phosphorylation and acetylation of the NF-kappaB signaling
      pathway.
AB  - This study investigated the inhibitory effect of gallic acid (GA) on the release
      of A Disintegrin and Metalloproteinase with Thrombospondin motifs 4 (ADAMTS4)
      through the regulation of the NF-kappaB signaling pathway, which is closely
      related to the matrix metalloproteinases in nucleus pulposus cells. Different
      concentrations of GA were added to TNF-alpha-induced human nucleus pulposus cells
      (hNPCs) and intervertebral disc degeneration rat model. ADAMTS-4 expression
      increased both in the TNF-alpha-induced nucleus pulposus cells and intervertebral
      disc degeneration rat model. By contrast, the release of ADAMTS-4 was reduced,
      and the TNF-alpha-induced apoptosis of nucleus pulposus cells was significantly
      inhibited after addition of GA at different concentrations. Further study found
      that the levels of phosphorylated p65 (p-p65) was increased and the classical NF
      kappaB signal pathway was activated after the nucleus pulposus cells were
      stimulated by TNF-alpha. Meanwhile, GA suppressed the p65 phosphorylation and
      inceased p65 deacetylation levels. As a consequence, GA can decrease the
      expression of ADAMTS-4 in nucleus pulposus cells by regulating the
      phosphorylation and acetylation of p65 in NF-kappaB signaling pathways.

PMID- 28512265
TI  - Chaetocin enhances dendritic cell function via the induction of heat shock
      protein and cancer testis antigens in myeloma cells.
AB  - Dendritic cells (DC)-based vaccines are considered useful in cancer immuno
      therapy, and the interactions of DC and dying tumor cells are important and
      promising for cancer immunotherapy. We investigated whether chaetocin could be
      used to induce death of myeloma cells, for loading onto DCs can affect DCs
      function. In this study, we show that the dying myeloma cells treated with
      chaetocin resulted in the induction of heat shock protein (HSP) 90, which was
      inhibited by antioxidant N-acetyl cysteine, and showed an increase in the
      expression of MAGE-A3 and MAGE-C1/CT7. DCs loaded with chaetocin-treated dying
      myeloma cells produced low levels of IL-10 and enhanced the cross presentation of
      DCs. Additionally, these DCs most potently inhibited regulatory T cells, induced
      Th1 polarization and activated myeloma-specific cytotoxic T lymphocytes compared
      with DCs loaded with UVB-irradiated dying myeloma cells. These results suggest
      that the pretreatment of myeloma cells with chaetocin can enhance DC function
      through the up-regulation of HSP90 and cancer testis antigens in dying myeloma
      cells and can potently induce the Th1 polarization of DCs and myeloma-specific
      cytotoxic T lymphocytes.

PMID- 28512268
TI  - Advance directives: cancer patients' preferences and family-based decision
      making.
AB  - BACKGROUND: Advance directives are a sensitive issue among traditional Chinese
      people, who usually refrain from mentioning this topic until it is imperative.
      Medical decisions for cancer patients are made by their families, and these
      decisions might violate patients' personal will. OBJECTIVES: This study aimed to
      examine the acceptance of advance directives among Chinese cancer patients and
      their families and patient participation in this procedure and, finally, to
      analyze the moral risk involved. RESULTS: While 246 patients and their family
      members refused official discussion of an advance directive, the remaining 166
      patients and their families accepted the concept of an advance directive and
      signed a document agreeing to give up invasive treatment when the anti-cancer
      treatment was terminated. Of these, only 24 patients participated in the decision
      making. For 101 patients, anti-cancer therapy was ended prematurely with as many
      as 37 patients not told about their potential loss of health interests. MATERIALS
      AND METHODS: Participants were 412 adult cancer patients from 9 leading hospitals
      across China. An advance directive was introduced to the main decision makers for
      each patient; if they wished to sign it, the advance directive would be
      systematically discussed. A questionnaire was given to the oncologists in charge
      of each patient to evaluate the interaction between families and patients,
      patients' awareness of their disease, and participation in an advance directive.
      CONCLUSIONS: Advance directives were not widely accepted among Chinese cancer
      patients unless anti-cancer therapy was terminated. Most cancer patients were
      excluded from the discussion of an advance directive.

PMID- 28512266
TI  - Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile
      xanthogranuloma.
AB  - Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually
      benign and self-limiting. We present a case of atypical, aggressive JXG harboring
      a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1
      gene, which encodes mitogen-activated protein kinase 1 or extracellular signal
      regulated 2 (ERK2). Our analysis revealed that the mutation results in
      constitutive ERK activation that is resistant to BRAF or MEK inhibitors but
      susceptible to an ERK inhibitor. These data highlight the importance of
      identifying specific MAPK pathway alterations as part of the diagnostic workup
      for patients with histiocytic disorders rather than initiating empiric treatment
      with MEK inhibitors.

PMID- 28512270
TI  - Abscopal Effect: Propitious or Pernicious?
AB  - Recent advances in the field of radiation biology have increased our knowledge of
      cellular responses to radiation and microenvironmental disseminations through
      radiation at molecular level.

PMID- 28512269
TI  - Oscillating expression of interleukin-16 in multiple myeloma is associated with
      proliferation, clonogenic growth, and PI3K/NFKB/MAPK activation.
AB  - Multiple myeloma (MM) is an incurable hematologic malignancy emerging from a
      plasma cell clone located in the bone marrow and is characterized by a high rate
      of fatal relapses after initially effective treatment. We have previously
      identified Interleukin-16 (IL-16) as an important factor promoting the
      proliferation of MM cells. We demonstrate here an upregulated, periodic
      expression, and secretion of IL-16 by MM cells leading to high extracellular IL
      16 levels. The level of IL-16 released from a given MM cell line correlated with
      its proliferative activity. Establishing an inducible knockdown system and
      performing gene expression arrays we observed an association between IL-16
      expression and activation of PI3, NFkappaB and MAP kinase pathways and,
      specifically, genes involved in tumor cell proliferation. Functional assays
      showed that IL-16 knockdown reduced the proliferative activity with a significant
      delay in cell cycle progression to G2 phase of conventional MM cells and
      completely suppressed the growth of clonogenic MM cells, which are suspected to
      be responsible for the high relapse rates in MM. Overall, our results demonstrate
      that tumor-regenerating MM cells may be particularly susceptible to IL-16
      neutralization, suggesting an important role of anti-IL-16 therapies in the
      treatment of MM, particularly in combination with existing strategies targeting
      the bulk of myeloma cells.

PMID- 28512271
TI  - Staining Beverages and Cigarette Smoke on Composite Resin and Human Tooth
      Fluorescence by Direct Spectrometry.
AB  - INTRODUCTION: This study evaluated the fluorescence intensity (FI) of different
      brands of composite resins (CRs) and compare those values with the FI of human
      tooth, under the action of cigarette smoke (CI), coffee (CA), and soft drink
      (CO), measured by direct spectrometry. MATERIALS AND METHODS: A total of 30
      specimens of each brand (Filtek Z350, Esthet-X, Amelogen, Durafill) were made.
      Others 30 tooth specimens (3 mm/diameter) were obtained from human molars using a
      trephine bur. The specimens were randomly divided into three groups (n = 10),
      according to substances: CI, CA, CO. The FI was directly measured using an optic
      fiber associated with a spectrometer and was measured at baseline and after
      staining. Data were submitted to Kruskal-Wallis, Dunnett, and Dunn tests.
      RESULTS: Staining influenced FI mean values among CRs and between those with
      human tooth. Z showed the closest FI mean values of tooth after staining.
      CONCLUSION: Staining beverages and cigarette smoke negatively influenced on FI of
      CR and human tooth. CLINICAL SIGNIFICANCE: The study shows darkening treatments
      influenced on the fluorescent property of the dental tissues and restorative
      materials according to the direct spectrometry analysis.

PMID- 28512272
TI  - Apical Periodontitis and Endodontic Treatment in Patients with Type II Diabetes
      Mellitus: Comparative Cross-sectional Survey.
AB  - AIMS: The aims of this study were to investigate the prevalence of apical
      periodontitis (AP) in diabetes mellitus (DM) patients compared with nondiabetic
      patients and to examine the effect of glycemic control on the prevalence of AP.
      MATERIALS AND METHODS: Radiographs of a group of DM patients were compared with
      those of a matched nondiabetic group to identify AP. The diabetic group was
      subdivided according to the level of glycemic control into two subgroups: A well
      controlled DM and a poorly controlled DM. The periapical index score was used to
      assess the periapical status. All groups were compared in regard to the presence
      of AP lesions, the number of end-odontically treated teeth (ET), and the
      percentage of failure of endodontically treated teeth (AP/ET ratio). Statistical
      Package for the Social Sciences (SPSS version 20.0, Chicago, Illinois, USA) was
      used for all the analyses; p <= 0.05 was considered as statistically significant.
      RESULTS: The prevalence of AP was higher in diabetic group than in the
      nondiabetic group (13.5 vs 11.9% respectively). Diabetic group had more teeth
      with endodontic treatment ET compared with nondiabetic group (4.18 vs 1.82%
      respectively); this difference was statistically significant (p = 0.001) along
      with higher AP/ET ratio (27.7 vs 19.3 respectively). The poorly controlled DM
      group had a higher prevalence of AP lesions compared with the well-controlled DM
      group (18.29 vs 9.21 respectively). This difference was statistically significant
      (p = 0.001); they also had a higher percentage of ET (5.55 vs 3.13% respectively)
      and AP/ ET ratio (32.0 vs 21.8% respectively). CONCLUSION: This survey
      demonstrates a higher prevalence of AP in DM patients compared with nondiabetic
      group, with an increased prevalence of persistent chronic AP. Compared with a
      well-controlled diabetic group, a poor glycemic control may be associated with a
      higher prevalence of AP and increased rate of endodontic failures. CLINICAL
      SIGNIFICANCE: Counseling diabetic patients, particularly those with poor glycemic
      control, about the risk of failure of endodontic treatment can be part of
      planning management, which could include refereeing diabetic patients who need
      endodontic treatment for consultant care.

PMID- 28512273
TI  - Comparison of Complications in Removable Mandibular Acrylic Splint and Cantilever
      Herbst for Management of Class II Malocclusion: A Retrospective Study.
AB  - INTRODUCTION: Numerous appliances are present for the management of class II
      malocclusion. We have conducted a study to compare the clinical complications
      during treatment with either a removable mandibular acrylic splint (RMS) or with
      a cantilever Herbst (HC) appliance for the management of class II malocclusion.
      MATERIALS AND METHODS: This study consisted of records of 114 patients (61 males,
      53 females), who were divided into two groups. Group I received RMS and group II
      received HC for the treatment of class II, Division 1 malocclusion. They were
      further subdivided according to the telescopic system used [Dentaurum type I or
      propulsor mandibular abzil (PMA)] and fixation mode (splint with crowns or
      GripTite bands). Patients' clinical records were assessed to identify clinical
      complications. RESULTS: The results of the study showed that the incidence of
      complications during treatment in both groups was statistically nonsignificant.
      The complications with either crown or band were also statistically
      nonsignificant. The Dentaurum group showed more susceptibility to complications
      than the PMA group. CONCLUSION: The PMA telescopic system is more efficient as
      compared with Dentaurum. Complication resulting from Herbst appliance is
      independent type of appliance used and mode of fixation. CLINICAL SIGNIFICANCE:
      Herbst appliance is the treatment of choice for class II malocclusion.

PMID- 28512274
TI  - Glucose Transporter 1 Expression in Odontogenic Keratocyst, Dentigerous Cyst, and
      Ameloblastoma: An Immunohistochemical Study.
AB  - INTRODUCTION: An array of odontogenic lesions manifest in the maxillofacial
      region with variable presentations. The biological behavior of lesions, such as
      odontogenic keratocyst (OKC), dentigerous cyst (DC), and ameloblastoma (AM)
      always invite debate. Glucose transporter 1 (GLUT-1) is proven to be an indicator
      of metabolic behavior of several benign and malignant neoplasms. AIM: The purpose
      of this study was to evaluate the expression of GLUT-1 in OKC, DC, and AM to
      understand their metabolic behavior. MATERIALS AND METHODS: Immunohistochemical
      expression of GLUT-1 was evaluated in each of the 15 cases of OKC, DC, and AM.
      The number of labeled cells, staining intensity, and membrane or cytoplasmic
      expressions were the parameters assessed and analyzed using chi-square test.
      RESULTS: All cases showed positive GLUT-1 expression: 86.6% OKC showed more than
      50% labeled cells followed by DC (40%) and AM (26.5%); 53.3% OKC showed strong
      intensity in comparison to AM, which showed weak intensity in 53.3% cases; 86.6%
      of OKCs showed both membrane and cytoplasmic expression followed by DC (40%) and
      AM (26.6%), whereas 73.3% of AM showed only membrane expression followed by DC
      (60%) and OKC (13.3%). CONCLUSION: Odontogenic keratocyst was found out to be
      more metabolically active followed by DC and AM.

PMID- 28512275
TI  - Knowledge, Attitude, and Practice of Pregnant Women regarding Oral Health Status
      and Treatment Needs following Oral Health Education in Pune District of
      Maharashtra: A Longitudinal Hospital-based Study.
AB  - INTRODUCTION: Pregnancy is a natural process that may create some changes in
      different parts of the body including the oral cavity. These changes will lead to
      oral diseases if enough and timely care of oral cavity is not taken. Women may
      experience increased gingivitis or pregnancy gingivitis beginning in the second
      or third month of pregnancy that increases in severity throughout the duration of
      pregnancy. To motivate the patient toward oral health and implement the needed
      prophylactic measures, a longitudinal study was planned to observe the effect of
      oral health education during pregnancy on knowledge, attitude, practice, oral
      health status, and treatment needs (TNs) of pregnant women belonging to different
      socioeconomic groups. MATERIALS AND METHODS: A longitudinal study was conducted
      among 112 pregnant women belonging to different socioeconomic groups to assess
      the effect of oral health education on knowledge, attitude, practice, oral health
      status, and TNs. The demographic details, knowledge, attitude, and practice of
      pregnant women, and oral health status were collected through a predesigned
      questionnaire by a principal investigator through an interview. Oral health
      examination was carried out to assess oral health status using revised World
      Health Organization Proforma 1997, and oral health education was given through
      PowerPoint presentation to the participants in local language, i.e., Marathi,
      after collecting the baseline data. Reinforcement of oral health education and
      blanket referral was done at 14th week, and follow-up data were collected at 28th
      week of gestation. The demographic details, such as age, sex, education,
      occupation, income, and the questions based on knowledge, attitude, and practice
      among participants were analyzed using number, percentage, and mean. RESULTS: At
      baseline, knowledge was limited, attitude was positive, while the practice was
      poor regarding oral health care during pregnancy in pregnant women belonging to
      different socioeconomic groups. After oral health education and blanket referral,
      at 28th week of gestation, knowledge regarding oral health care improved
      drastically, attitude toward oral health became more positive, whereas practice
      did not change much among all the pregnant women belonging to different
      socioeconomic groups, probably indicating sociocultural influences. CONCLUSION:
      Intensive oral health education during pregnancy leads to drastic improvement in
      knowledge and attitude. Practice, gingival health, and the number of filled teeth
      also improved to some extent. CLINICAL SIGNIFICANCE: Regular oral health
      education programs should be conducted at community level among pregnant woman to
      reduce the burden of oral diseases.

PMID- 28512276
TI  - Osteoporosis Knowledge and Related Health Behavior among Women in Jazan Region,
      Kingdom of Saudi Arabia.
AB  - INTRODUCTION: Osteoporosis is a systemic bone disease that can be prevented to
      some extent by awareness of its risk factors and related health behavior. The aim
      of this study was to collect information about knowledge and awareness of
      osteoporosis among women living in Jazan and to describe the type of food habits,
      sociodemographic characteristics, and other osteoporosis-related health behavior.
      MATERIALS AND METHODS: Self-administered questionnaires were used for data
      collection. The total participants were 546 women: 88 (16.1%) were health
      professionals and 458 (83.9%) non health professionals in the age range <=20 to
      50 years. Data collection was facilitated by a trained intern female doctor of
      dentistry whose task was to administer the distribution and collection of the
      questionnaires. RESULTS: In total, 61.9% of health professionals and 54.3% of
      nonhealth professionals scored highly on knowledge of osteoporosis. The
      respondents of osteoporosis preventive food items were also highly knowledgeable
      with 50.6 and 52.6% of health and nonhealth professionals respectively. About
      48.1% of health professional and 44.2% of nonhealth professional scored low on
      knowledge of osteoporosis behavior and attitude, vitamin supplements, and
      sunlight exposure. The age effect on osteoporosis knowledge was 33.8% in young
      age group and 30.7% in old age group. CONCLUSION: Our study shows that Jazan
      women were highly knowledgeable and aware about osteoporosis and its related
      health behavior and that health professionals and nonhealth professionals were
      equally aware about osteoporosis-related health matters. CLINICAL SIGNIFICANCE:
      Awareness and preventive behavior of osteoporosis can prevent or slow the
      development of the disease.

PMID- 28512277
TI  - Accuracy of Working Length Determination using NovApex and Root-ZX Apex Locators:
      An in vitro Study.
AB  - INTRODUCTION: This ex vivo study evaluated the accuracy of the Root-ZX electronic
      apex locator (EAL) (J. Morita, Tokyo, Japan) and the NovApex (Forum Technologies,
      Rishon Lezion, Israel) in determining the working length (WL) during endodontic
      treatment. MATERIALS AND METHODS: Forty extracted single-rooted human teeth were
      selected for this study. The actual WL was measured with visual technique by a
      size #15 k-file under magnification. Then, the canal lengths were measured
      electronically with both Root-ZX and NovApex apex locators within +/-0.5 and +/-1
      mm. Mean percentage of data was analyzed between groups using paired t-test, with
      a statistically significant level of p < 0.05. RESULTS: The accuracy of NovApex
      apex locator was 85% within +/-0.5 mm and 92.5% within +/-1 mm. The accuracy of
      Root-ZX apex locator was 70% within +/-0.5 mm and 97.5% within +/-1 mm. There was
      no significant difference between the accuracy of the two EALs. CONCLUSION: Both
      the NovApex and Root-ZX EALs are useful for measuring the WL with high accuracy.
      CLINICAL SIGNIFICANCE: Given the importance of accurate WL determination in the
      success of endodontic treatments, the accuracy of different apex locators should
      be evaluated.

PMID- 28512278
TI  - Use of Collagen Matrix for Augmentation of the Peri-implant Soft Tissue at the
      Time of Immediate Implant Placement.
AB  - AIM: The aim of this study was to determine the treatment outcome of the use of a
      porcine monolayer collagen matrix (mCM) to augment peri-implant soft tissue in
      conjunction with immediate implant placement as an alternative to patient's own
      connective tissue. MATERIALS AND METHODS: A total of 27 implants were placed
      immediately in 27 patients (14 males and 13 females, with a mean age of 52.2
      years) with simultaneous augmentation of the soft tissue by the use of a mCM. The
      patients were randomly divided into two groups: Group I: An envelope flap was
      created and mCM was left coronally uncovered, and group II: A coronally
      repositioned flap was created and the mCM was covered by the mucosa. Soft-tissue
      thickness (STTh) was measured at the time of surgery (T0) and 6 months
      postoperatively (T1) using a customized stent. Cone beam computed tomographies
      (CBCTs) were taken from 12 representative cases at T1. A stringent plaque control
      regimen was enforced in all the patients during the 6-month observation period.
      RESULTS: Mean STTh change was similar in both groups (0.7 +/- 0.2 and 0.7 +/- 0.1
      mm in groups I and II respectively). The comparison of STTh between T0 and T1
      showed a statistically significant increase of soft tissue in both groups I and
      II as well as in the total examined population (p < 0.001). The STTh change as
      well as matrix thickness loss were comparable in both groups (p > 0.05). The
      evaluation of the CBCTs did not show any signs of resorption of the buccal bone
      plate. CONCLUSION: Within the limitations of this study, it could be concluded
      that the collagen matrix used in conjunction with immediate implant placement
      leads to an increased thickness of peri-implant soft tissue independent of the
      flap creation technique and could be an alternative to connective tissue graft.
      CLINICAL SIGNIFICANCE: The collagen matrix used seems to be a good alternative to
      patient's own connective tissue and could be used for the soft tissue
      augmentation around dental implants.

PMID- 28512279
TI  - Antimicrobial Potential of Plant Extracts and Chemical Fractions of Sideroxylon
      obtusifolium (Roem. & Schult.) T.D. Penn on Oral Microorganisms.
AB  - AIM: The aim of this study is to evaluate the in vitro antimicrobial activity of
      plant extracts and chemical fractions of Sideroxylon obtusifolium T.D. Penn on
      Streptococcus mutans, Streptococcus oralis, Streptococcus salivarius,
      Streptococcus parasanguinis, and Candida albicans as well as to identify the
      chemical classes found in the bioactive extracts possessing better activity.
      MATERIALS AND METHODS: Freeze-dried hydroalcoholic extracts of the bark and
      leaves (LC and LF respectively) and ethanol extracts of bark and leaves (EC and
      EF respectively) of S. obtusifolium were assessed for antimicrobial potential by
      determining the minimum inhibitory concentration (MIC), minimum bactericidal
      concentration, and minimum fungicidal concentration (MFC). The tests were
      performed by microdilu-tion method (in triplicate) in three independent
      experiments. Phytochemical characterization was performed by quantification of
      total polyphenols, total flavonoids, and condensed tannins. RESULTS: The EC
      extract presented weak antimicrobial potential on the growth of S. mutans (MIC =
      1000 MUg/mL); all extracts showed moderate inhibitory activity on the growth of
      C. albicans (MIC = 500 MUg/mL). The dichloromethane and n-butanol fractions of LF
      extracts showed moderate growth inhibitory activity (MIC = 250 MUg/mL) on C.
      albicans and fungicide potential (MFC/MIC = 2). The phytochemical
      characterization revealed a predominance of total polyphenols (EC = 29.23%; LC =
      25.98%) and condensed tannins (LC = 38.84%; LF = 17.78%). CONCLUSION: The
      dichloromethane and n-butanol fractions of S. obtusifolium LF extract showed
      antifungal activity against C. albicans, with the potential for bioprospection of
      phytocom-pounds for the treatment of periodontal fungal diseases caused by this
      microorganism. The effect may be related to phyto-chemical compounds from the
      polyphenol and condensed tannin classes. CLINICAL SIGNIFICANCE: Research for new
      oral microbial disease treatment alternatives in bioactive compounds from
      medicinal plants is of clinical relevance and scientific interest since many
      therapeutic antifungal agents do not obtain the effectiveness expected due to
      microbial resistance, or to adverse effects on human tissues.

PMID- 28512280
TI  - Herpes Simplex 1 and Periopathogen Role in Peri-implantitis.
AB  - INTRODUCTION: The objectives of this study were to compare the qualitative and
      quantitative profiles of herpes simplex virus type I (HSV-1) in implant surfaces
      between participants with peri-implantitis (PI) and Healthy peri-implant tissues
      and to quantitatively assess the relation between HSV-1 and periopathogens inside
      the microbiological profile associated with PI. MATERIALS AND METHODS: A total of
      40 patients with PI and 40 with healthy peri-implant tissues (HI) were recruited.
      Plaque samples from peri-implant sulcus and internal implant connections were
      analyzed using quantitative real-time polymerase chain reaction to detect and
      quantify HSV-1 and periodonto-pathogens. Frequencies of detection and levels of
      microorganisms were compared between PI and HI; the frequencies and levels of
      periodontopathogens were compared between HSV-1+ and HSV-1- PI to assess
      qualitative relations between HSV-1 and bacteria. Correlation between HSV-1 and
      periodontopatho-gens levels was assessed in PI and HI. RESULTS: A total of 77
      dental implants affected by PI, and 113 HIs were included. The HSV-1 prevalence
      was slightly higher in PI compared with controls (33.3 vs 23.8%; p > 0.05); HSV-1
      was detected in external samples more frequently compared with internal samples.
      The HSV-1-positive patients revealed higher median loads of Prevotella intermedia
      (Pi) and Campylobacter rectus (Cr) compared with HSV-1-negative patients. In the
      PI group, a significant positive correlation was evidenced between HSV-1 and
      Tannerella forsythia, Parvimonas micra (Pm), Fusobacterium nucleatum, and Cr
      levels, while in the HI, positive correlation between HSV-1 and Aggregatibacter
      actinomycetemcomitans, Pi, and Pm was established. CONCLUSION: The HSV-1
      prevalence cannot be used to identify PI. The HSV-1 was found in similar levels
      of PI and HI patients after an average of 6 years of loaded implants. The HSV-1
      prevalence cannot be used to identify implants with or without the presence of
      PI. CLINICAL SIGNIFICANCE: Although HSV-1 is detected in PI site, HSV-1 may
      represent an unspecific indicator for the host response to the bacterial
      challenge observed in PI.

PMID- 28512281
TI  - Intricate Assessment and Evaluation of Long-term Implant Success as affected by
      Clinicomicrobial and Salivary Diagnostics in Type II Diabetic Patients: A
      Longitudinal Study.
AB  - INTRODUCTION: Replacement of missing teeth by dental implants is one of the most
      common methods employed these days. Because of significant advancement in the
      design of implants and modifications in the procedure of dental implant surgery,
      the survival rate of the dental implants has reached up to approximately 95%.
      Osseointegration is one of the important factors affecting the survival of dental
      implants. Apart from these, the body's physiologic alterations can also
      predispose the dental implants for failure. Diabetes is one such metabolic
      disease characterized by abnormal or delayed wound healing. Hence, we assessed
      the clinicomicrobial and salivary profile of diabetic patients undergoing
      rehabilitation by dental implants. MATERIALS AND METHODS: This study included
      diabetic patients who underwent dental implant surgeries for prosthetic
      rehabilitation. Follow-up records of the patients' up to 1 year were maintained.
      Various clinicoradiographic and periodontal parameters were measured at various
      time intervals during follow-up time; 25 mL of salivary and blood sample was
      taken from all the subjects and was sent to the laboratories for assessment of
      various salivary biomarkers. All the results were analyzed by Statistical Package
      for the Social Sciences software. RESULTS: The mean level of interleukin-p at
      baseline time was found to be 2.38 and 2.21 in diabetic group and control group
      respectively. While comparing the levels of osteoprotegerin in both study groups,
      a significant correlation was obtained. In diabetic and control group, 62 and 61
      years was the mean age of the patients respectively. No significant correlation
      was obtained while comparing the microbial flora of diabetic and control group.
      CONCLUSION: In both diabetic and nondiabetic patients, similar microbial,
      salivary marker, and clinicoradiological patterns were seen. CLINICAL
      SIGNIFICANCE: Diabetic patients who maintain their body's metabolic rate show
      similar success rate of dental implants as seen in nondiabetic patients.

PMID- 28512282
TI  - Orthopedic Effect of Chin Cup during Mixed Dentition Stage.
AB  - INTRODUCTION: Chin cup (CC) therapy has been used as the traditional appliance
      for treating class III malocclusion during mixed dentition period. The aim of
      this study was to investigate the effect of CC on the improvement of skeletal and
      dentoalveo-lar skeletal changes in class III patients during mixed dentition
      stage. MATERIALS AND METHODS: A total of 30 patients (7-9 years old) with
      skeletal class III malocclusion were selected based on clinical and cephalometric
      examination. Out of 30 patients, 20 underwent CC therapy. All orthodontic records
      and measurements were taken before and after treatment. Similar records were
      collected from the control group. The lateral cephalometric films were traced
      before and after treatment and analyzed. RESULTS: There was a significant
      improvement in maxillary and the mandibular skeletal measurements after CC
      therapy. Improvement of ANB angle and an increase in Wits appraisal have been
      detected in the treated group according to intermaxillary skeletal variables.
      CONCLUSION: The study concluded that the CC therapy is effective for correcting
      skeletal class III malocclusion along with positive changes in the dentoskeletal
      variables during the mixed dentition stage.

PMID- 28512283
TI  - Unusual Root Canal Irrigation Solutions.
AB  - Microorganisms and their by-products play a critical role in pulp and
      periradicular pathosis. Therefore, one of the main purposes of root canal
      treatment is disinfection of the entire system of the canal. This aim may be
      obtained using mechanical preparation, chemical irrigation, and temporary
      medication of the canal. For this purpose, various irrigation solutions have been
      advocated. Common root canal irrigants, such as sodium hypochlorite,
      chlorhexidine, and a mixture of tetracycline, acid, and detergent have been
      extensively reviewed. The aim of this review was to address the less common newer
      root canal irrigation solutions, such as citric acid, maleic acid,
      electrochemically activated water, green tea, ozonated water, and SmearClear.

PMID- 28512284
TI  - Improved Survival in Patients with Resected Pancreatic Carcinoma Using
      Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial
      Infusion Chemotherapy.
AB  - BACKGROUND We assessed the role of adjuvant intensity-modulated radiotherapy
      (IMRT) in combination with chemotherapy for pancreatic carcinomas after curative
      resection and identified prognostic factors related to pancreatic carcinoma after
      multidisciplinary treatment strategies. MATERIAL AND METHODS Pancreatic carcinoma
      patients (n=61) who received adjuvant radiotherapy after resection (median dose,
      50.4 Gy) between 2010 and 2016 were retrospectively identified. Sixty patients
      received chemotherapy, including concurrent chemoradiotherapy (CCRT), systemic
      chemotherapy, and regional intra-arterial infusion chemotherapy (RIAC). The
      Kaplan-Meier method was used to measure the 3-year overall survival (OS) and
      disease-free survival (DFS) rates. Log-rank univariate analysis and multivariate
      Cox regression model analysis were used to identify prognostic factors. RESULTS
      Median follow-up time was 25.5 (range, 4.9-59.7) months. The 3-year OS and DFS
      rates were 31.0% and 16.1%, respectively. The median OS and DFS were 27.4 and
      16.7 months, respectively. Multivariate analysis indicated that independent
      favorable predictors for OS were CCRT (p=0.039) and postoperative RIAC (p=0.044).
      Moreover, postoperative RIAC (p=0.027), and pre-radiotherapy CA19-9 <=37 U/mL
      (p=0.0080) were independent favorable predictors for DFS. The combination of
      radiotherapy and chemotherapy was tolerated well by the patients, and no
      treatment-related death occurred. CONCLUSIONS Combined IMRT and adjuvant
      chemotherapy appeared safe and effective for pancreatic carcinoma. CCRT was
      associated with improved survival with acceptable toxicity. We propose that
      radiotherapy could be a part of postoperative treatment, but it should be
      administered concurrently with chemotherapy. Adding RIAC was associated with
      improved OS and DFS and it could be integrated into the postoperative treatment
      regimen.

PMID- 28512285
TI  - Coronary Aneurysm Formation After Bioresorbable Vascular Scaffold Implantation
      Resulting in Acute Myocardial Infarction.
AB  - BACKGROUND Development of a true coronary aneurysm after percutaneous coronary
      intervention is a rare event, and a coronary aneurysm resulting in acute
      myocardial infarction is even rarer. Coronary aneurysm formation after
      bioresorbable vascular scaffold (BVS) implantation, eventually leading to
      thrombosis, embolization, and myocardial infarction, has never been reported
      before in the literature. CASE REPORT A 62-year-old man received an elective BVS
      for a proximal left anterior descending lesion. Two months later, he suffered
      from a non-ST-segment myocardial infarction. Coronary angiography showed a non
      significant distal stent edge restenosis over the left anterior descending artery
      and a small aneurysm after the first diagonal branch. A XIENCE Xpedition stent
      was used to cover both lesions and final angiography showed shrinkage of the
      aneurysm and resolution of the restenosis. CONCLUSIONS Since a consensus or an
      established treatment guideline for treating coronary aneurysms is currently
      lacking, each case should be treated with caution and should be guided by the
      accompanying circumstances presented during the procedure. Although size,
      rapidity of growth, and the presence of high-risk features are the main
      determinants of whether to treat the lesion, the inherent risk of restenosis or
      reocclusion after use of drug-eluting stents and the coronary intervention
      procedure itself should also be taken into consideration. However, one must not
      take lightly a small coronary aneurysm when discovered, as the abnormal fluid
      dynamics inside may result in thrombus formation and embolization. The
      fundamental technical aspects of stent deployment, such as avoiding
      overstretching during lesion preparation, use of balloons shorter than the
      implanted device, and normal-to-normal or healthy "landing zone" of the device,
      should be followed.

PMID- 28512286
TI  - Multifaceted catalytic hydrogenation of amides via diverse activation of a
      sterically confined bipyridine-ruthenium framework.
AB  - Amides are ubiquitous and abundant in nature and our society, but are very stable
      and reluctant to salt-free, catalytic chemical transformations. Through the
      activation of a "sterically confined bipyridine-ruthenium (Ru) framework
      (molecularly well-designed site to confine adsorbed H2 in)" of a precatalyst,
      catalytic hydrogenation of formamides through polyamide is achieved under a wide
      range of reaction conditions. Both C=O bond and C-N bond cleavage of a lactam
      became also possible using a single precatalyst. That is, catalyst diversity is
      induced by activation and stepwise multiple hydrogenation of a single precatalyst
      when the conditions are varied. The versatile catalysts have different structures
      and different resting states for multifaceted amide hydrogenation, but the common
      structure produced upon reaction with H2, which catalyzes hydrogenation, seems to
      be "H-Ru-N-H."

PMID- 28512287
TI  - Levels of Faecal Calprotectin and Magnetic Resonance Enterocolonography Correlate
      with Severity of Small Bowel Crohn's Disease: A Retrospective Cohort Study.
AB  - Few studies have evaluated the usefulness of fecal calprotectin (FC) or magnetic
      resonance enterography (MRE) in diagnosing active Crohn's disease (CD) of the
      small bowel. In the study, we investigated the reliability of FC and MRE in
      assessing the activity of ileal CD and further explored the relationship between
      levels of FC and MRE scores. A total of 221 patients were diagnosed with ileal or
      ileo-colitis CD in our department between July 2012 and October 2016. The global
      magnetic resonance index of activity (MaRIA) correlated with the simple
      endoscopic score for CD (SES-CD) (r = 0.527, P = 0.005). When analysed segment-by
      segment, a significant correlation was still observed (r = 0.590, P < 0.001). The
      SES-CD correlated closest with FC (r = 0.503), followed by CRP (r = 0.461), ESR
      (0.377) and the CDAI (r = 0.320). In receiver operating characteristic (ROC)
      analyses, the FC cut-off value of mucosal healing was 213.1 MUg/g, with 76.1%
      sensitivity and 66.7% specificity. As for MaRIA, a cut-off value of 6.8 for each
      segment provided a sensitivity of 100% and a specificity of 79.2%. No agreement
      between MaRIA and FC levels was found. In conclusion, a combination of FC levels
      and MaRIA could be effective in monitoring mucosal activity in patients with
      small bowel CD.

PMID- 28512289
TI  - A genetic screen in combination with biochemical analysis in Saccharomyces
      cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular
      trafficking and autophagy.
AB  - The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA)
      protects plants, mammals and humans effectively against various fungal pathogens.
      However, the mechanism by which PCA inhibits or kills fungal pathogens is not
      fully understood. We analyzed the effects of PCA on the growth of two fungal
      model organisms, Saccharomyces cerevisiae and Candida albicans, and found that
      PCA inhibited yeast growth in a dose-dependent manner which was inversely
      dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in
      a dose-dependent manner as pH increased. We then screened a yeast mutant library
      to identify genes whose mutation or deletion conferred resistance or sensitivity
      to PCA. We isolated 193 PCA-resistant or PCA-sensitive mutants in clusters,
      including vesicle-trafficking- and autophagy-defective mutants. Further analysis
      showed that unlike hygromycin B, PCA significantly altered intracellular
      vesicular trafficking under growth conditions and blocked autophagy under
      starvation conditions. These results suggest that PCA inhibits or kills
      pathogenic fungi in a complex way, in part by disrupting vesicular trafficking
      and autophagy.

PMID- 28512288
TI  - Lactic acid bacteria-specific induction of CD4+Foxp3+T cells ameliorates shrimp
      tropomyosin-induced allergic response in mice via suppression of mTOR signaling.
AB  - The beneficial effects of probiotics have been described in allergic
      sensitization and diseases; however, many questions remain unanswered, such as
      characteristics of the most effective strains in modulation of allergic responses
      and how orally administered probiotics affect the systemic immune system. In the
      present work, oral administration of five lactic acid bacteria strains showed
      variable effects on protection against the allergic reaction in a mouse model of
      food allergy to shrimp tropomyosin (ST). The most effective anti-allergic strain,
      Bacillus coagulans 09.712 (Bc), greatly improved epithelial barrier function and
      increased lymphocytes proliferation. Moreover, Bc suppresses ST sensitization by
      altering Th1/Th2/Treg balance as a result of strong induction of CD4+Foxp3+Tregs
      in combination with IL-10 producing. Bc-specific induction of CD4+Foxp3+ Tregs
      also suppresses Th17 pro-inflammatory response in this mouse model. Finally, the
      intake of Bc suppresses mTOR activation and thus the phosphorylation of
      downstream factors. Inhibition of mTOR signaling by Bc further results in FOXP3
      up-regulation and GATA-3 down-regulation, which, in turn, facilitate to control
      Th2-predominant and Th17 pro-inflammatory responses caused by ST. Our work
      provides further characterization of the anti-allergic effects of probiotic LAB
      strains, and identifies new targets for preventive and curative treatment of food
      allergies.

PMID- 28512290
TI  - Evolution of Drug-resistant Acinetobacter baumannii After DCD Renal
      Transplantation.
AB  - Infection after renal transplantation remains a major cause of morbidity and
      death, especially infection from the extensively drug-resistant bacteria, A.
      baumannii. A total of fourteen A. baumannii isolates were isolated from the
      donors' preserved fluid from DCD (donation after cardiac death) renal
      transplantation and four isolates in the recipients' draining liquid at the
      Kidney Disease Center, The First Affiliated Hospital, College of Medicine,
      Zhejiang University, from March 2013 to November 2014. An outbreak of A.
      baumannii emerging after DCD renal transplantation was tracked to understand the
      transmission of the pathogen. PFGE displayed similar DNA patterns between
      isolates from the same hospital. Antimicrobial susceptibility tests against
      thirteen antimicrobial agents were determined using the K-B diffusion method and
      eTest. Whole-genome sequencing was applied to investigate the genetic
      relationship of the isolates. With the clinical data and research results, we
      concluded that the A. baumannii isolates 3R1 and 3R2 was probably transmitted
      from the donor who acquired the bacteria during his stay in the ICU, while
      isolate 4R1 was transmitted from 3R1 and 3R2 via medical manipulation. This study
      demonstrated the value of integration of clinical profiles with molecular methods
      in outbreak investigation and their importance in controlling infection and
      preventing serious complications after DCD transplantation.

PMID- 28512292
TI  - Effects of treadmill running with different intensity on rat subchondral bone.
AB  - Subchondral bone (SB) is recognized as a key factor in normal joint protection,
      not only does it provide a shock absorbing and supportive function for the
      cartilage, but it may also be important for cartilage metabolism. Mechanical
      loading is considered to be a critical regulator of skeletal homeostasis,
      including bone and cartilage. It is suggested that both cartilage and bone may
      respond to mechanical loading in an intensity-dependent manner. In this report,
      we have discovered that the subchondral plate became thicker with higher bone
      mineral density (BMD) and lower porosity, while trabecular bone became more plate
      like and denser with higher BMD in high-intensity running (HIR) group. Further,
      HIR led to highly remodeled, less mineralized, and stiffer subchondral plate and
      trabecular bone. On the contrary, low-intensity running and moderate-intensity
      running failed to result in considerable changes in microstructure, composition
      and hardness. Our findings suggested that running affects SB in an intensity
      dependent manner. In addition, HIR may induce change in organization and
      composition of SB, and consequently alter its mechanical properties. HIR-induced
      "brittle and stiff" SB may adversely affect the overlying articular cartilage.

PMID- 28512291
TI  - Characterization of Mechanically Matched Hydrogel Coatings to Improve the
      Biocompatibility of Neural Implants.
AB  - Glial scar is a significant barrier to neural implant function. Micromotion
      between the implant and tissue is suspected to be a key driver of glial scar
      formation around neural implants. This study explores the ability of soft
      hydrogel coatings to modulate glial scar formation by reducing local strain. PEG
      hydrogels with controllable thickness and elastic moduli were formed on the
      surface of neural probes. These coatings significantly reduced the local strain
      resulting from micromotion around the implants. Coated implants were found to
      significantly reduce scarring in vivo, compared to hard implants of identical
      diameter. Increasing implant diameter was found to significantly increase
      scarring for glass implants, as well as increase local BBB permeability, increase
      macrophage activation, and decrease the local neural density. These results
      highlight the tradeoff in mechanical benefit with the size effects from
      increasing the overall diameter following the addition of a hydrogel coating.
      This study emphasizes the importance of both mechanical and geometric factors of
      neural implants on chronic timescales.

PMID- 28512293
TI  - Near Infrared Quantum Cutting Luminescence of Er3+/Tm3+ Ion Pairs in a Telluride
      Glass.
AB  - The multiphoton near-infrared, quantum cutting luminescence in Er3+/Tm3+ co-doped
      telluride glass was studied. We found that the near-infrared 1800-nm luminescence
      intensity of (A) Er3+(8%)Tm3+(0.5%):telluride glass was approximately 4.4 to 19.5
      times larger than that of (B) Tm3+(0.5%):telluride glass, and approximately 5.0
      times larger than that of (C) Er3+(0.5%):telluride glass. Additionally, the
      infrared excitation spectra of the 1800 nm luminescence, as well as the visible
      excitation spectra of the 522 nm and 652 nm luminescence, of (A)
      Er3+(8%)Tm3+(0.5%):telluride glass are very similar to those of Er3+ ions in (C)
      Er3+(0.5%):telluride glass, with respect to the shapes of their excitation
      spectral waveforms and peak wavelengths. Moreover, we found that there is a
      strong spectral overlap and energy transfer between the infrared luminescence of
      Er3+ donor ions and the infrared absorption of Tm3+ acceptor ions. The efficiency
      of this energy transfer {4I13/2(Er3+) -> 4I15/2(Er3+), 3H6(Tm3+) -> 3F4(Tm3+)}
      between the Er3+ and Tm3+ ions is approximately 69.8%. Therefore, we can conclude
      that the observed behaviour is an interesting multiphoton, near-infrared, quantum
      cutting luminescence phenomenon that occurs in novel Er3+-Tm3+ ion pairs. These
      findings are significant for the development of next-generation environmentally
      friendly germanium solar cells, and near-to-mid infrared (1.8-2.0 MUm) lasers
      pumped by GaN light emitting diodes.

PMID- 28512294
TI  - The potential use of cuticular hydrocarbons and multivariate analysis to age
      empty puparial cases of Calliphora vicina and Lucilia sericata.
AB  - Cuticular hydrocarbons (CHC) have been successfully used in the field of forensic
      entomology for identifying and ageing forensically important blowfly species,
      primarily in the larval stages. However in older scenes where all other
      entomological evidence is no longer present, Calliphoridae puparial cases can
      often be all that remains and therefore being able to establish the age could
      give an indication of the PMI. This paper examined the CHCs present in the lipid
      wax layer of insects, to determine the age of the cases over a period of nine
      months. The two forensically important species examined were Calliphora vicina
      and Lucilia sericata. The hydrocarbons were chemically extracted and analysed
      using Gas Chromatography - Mass Spectrometry. Statistical analysis was then
      applied in the form of non-metric multidimensional scaling analysis (NMDS),
      permutational multivariate analysis of variance (PERMANOVA) and random forest
      models. This study was successful in determining age differences within the empty
      cases, which to date, has not been establish by any other technique.

PMID- 28512296
TI  - Entanglement monogamy in three qutrit systems.
AB  - By introducing an arbitrary-dimensional multipartite entanglement measure, which
      is defined in terms of the reduced density matrices corresponding to all possible
      two partitions of the entire system, we prove that multipartite entanglement
      cannot be freely shared among the parties in both n-qubit systems and three
      qutrit systems. Furthermore, our result implies that the satisfaction of the
      entanglement monogamy is related to the number of particles in the quantum
      system. As an application of three-qutrit monogamy inequality, we give a
      condition for the separability of a class of two-qutrit mixed states in a 3 ? 3
      system.

PMID- 28512297
TI  - Flexible Two-Photon Interference Fringes with Thermal Light.
AB  - Flexible interference patterning is an important tool for adaptable measurement
      precisions. We report on experimental results of controllable two-photon
      interference fringes with thermal light in an incoherent rotational shearing
      interferometer. The two incoherent beams in the interferometer are orthogonally
      polarized, and their wavefront distributions differ only in an angle of rotation.
      The spacings and directions of the two-photon interference fringes vary with the
      rotation angle, as illustrated in three cases of two-photon correlation
      measurements in experiment.

PMID- 28512298
TI  - Genetic load makes cancer cells more sensitive to common drugs: evidence from
      Cancer Cell Line Encyclopedia.
AB  - Genetic alterations initiate tumors and enable the evolution of drug resistance.
      The pro-cancer view of mutations is however incomplete, and several studies show
      that mutational load can reduce tumor fitness. Given its negative effect, genetic
      load should make tumors more sensitive to anticancer drugs. Here, we test this
      hypothesis across all major types of cancer from the Cancer Cell Line
      Encyclopedia, which provides genetic and expression data of 496 cell lines
      together with their response to 24 common anticancer drugs. We found that the
      efficacy of 9 out of 24 drugs showed significant association with genetic load in
      a pan-cancer analysis. The associations for some tissue-drug combinations were
      remarkably strong, with genetic load explaining up to 83% of the variance in the
      drug response. Overall, the role of genetic load depended on both the drug and
      the tissue type with 10 tissues being particularly vulnerable to genetic load. We
      also identified changes in gene expression associated with increased genetic
      load, which included cell-cycle checkpoints, DNA damage and apoptosis. Our
      results show that genetic load is an important component of tumor fitness and can
      predict drug sensitivity. Beyond being a biomarker, genetic load might be a new,
      unexplored vulnerability of cancer.

PMID- 28512295
TI  - cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal
      neuronal cells.
AB  - Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble
      adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs).
      Both cAMP sources were shown to be required for the phosphorylation of ERK1/2
      triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and
      neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth
      arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells).
      By characterising CRHR1 signalling mechanisms involved in the neuritogenic
      effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by
      a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are
      involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation
      and c-fos induction, but only sAC-generated cAMP pools are critical for the
      neuritogenic effect of CRH, further highlighting the engagement of two sources of
      cAMP downstream of the activation of a GPCR, and reinforcing the notion that
      restricted cAMP microdomains may regulate independent cellular processes.

PMID- 28512299
TI  - Transgenic Bt rice lines producing Cry1Ac, Cry2Aa or Cry1Ca have no detrimental
      effects on Brown Planthopper and Pond Wolf Spider.
AB  - Transgenic rice expressing cry genes from the bacterium Bacillus thuringiensis
      (Bt rice) is highly resistant to lepidopteran pests. The brown planthopper (BPH,
      Nilaparvata lugens) is the main non-target sap-sucking insect pest of Bt
      transgenic rice. The pond wolf spider (PWS, Pardosa pseudoannulata) is one of the
      most dominant predators of BPH in rice fields. Consequently, the safety
      evaluation of Bt rice on BPH and PWS should be conducted before
      commercialization. In the current study, two experiments were performed to assess
      the potential ecological effects of Bt rice on BPH and PWS: (1) a tritrophic
      experiment to evaluate the transmission of Cry1Ac, Cry2Aa and Cry1Ca protein in
      the food chain; and (2) binding assays of Cry1Ac, Cry2Aa and Cry1Ca to midgut
      brush border membrane proteins from BPH and PWS. Trace amounts of the three Cry
      proteins were detected in BPH feeding on Bt rice cultivars, but only Cry1Ac and
      Cry2Aa proteins could be transferred to PWS through feeding on BPH. In vitro
      binding of biotinylated Cry proteins and competition assays in midgut protein
      vesicles showed weak binding, and ligand blot analysis confirmed the binding
      specificity. Thus, we inferred that the tested Bt rice varieties have negligible
      effects on BPH and PWS.

PMID- 28512300
TI  - Overview of influenza vaccination policy in Beijing, China: Current status and
      future prospects.
AB  - Vaccination is the best available way to prevent influenza infections and related
      complications. Little information is available on vaccination policy in the
      world's most populous country, China. In China, influenza vaccine is not included
      in the national immunization programme. Citizens seek the vaccine on their own.
      Since 2007, Beijing, ahead of most cities in China, has offered free influenza
      vaccine for seniors aged at least 60 years and for primary and middle school
      students. There has been limited evaluation of the policy. We introduce and
      evaluate the government-funded influenza immunization policy in Beijing.
      Available data showed that the policy greatly increased the vaccine uptake rate
      in the population qualifying for free vaccination. Evidence of impact in a single
      influenza season on all high-risk populations was unclear. We suggest that
      further evaluation over multiple influenza seasons and in each high-risk group
      are required to inform future policy development in Beijing.

PMID- 28512301
TI  - Maternal antioxidant provisioning mitigates pollutant-induced oxidative damage in
      embryos of the temperate sea urchin Evechinus chloroticus.
AB  - One mechanism of pollution resistance in marine populations is through
      transgenerational plasticity, whereby offspring capacity to resist pollution
      reflects parental exposure history. Our study aimed to establish correlations
      between oxidative stress biomarkers and key reproductive fitness parameters in
      the temperate sea urchin Evechinus chloroticus following exposure to dietary
      polycyclic aromatic hydrocarbons (PAHs). PAH-exposed adults exhibited total gonad
      tissue concentrations of PAHs in excess of 4 and 5 times baseline levels, for
      females and males respectively. Antioxidant enzymes were upregulated and
      oxidative lipid and protein damage to gonad tissues occurred. In addition, early
      stage offspring reflected maternal antioxidant status, with progeny derived from
      exposed females demonstrating significantly higher baselines than those derived
      from control females. Maternal exposure history enhanced the capacity of embryos
      to minimise oxidative damage to lipids and proteins following exposure to
      additional PAHs, but provided less of an advantage in protection against
      oxidative DNA damage. Abnormal embryonic development was largely independent of
      oxidative damage, remaining high in all embryo populations regardless of parental
      PAH-history. Overall, results document evidence for maternal transfer of
      antioxidant potential in E. chloroticus, but imply that a short-term inherited
      resilience against oxidative stress may not necessarily translate to a fitness or
      survival gain.

PMID- 28512302
TI  - Olfactory threshold and odor discrimination ability in children - evaluation of a
      modified "Sniffin' Sticks" test.
AB  - The clinical diagnostics of olfactory dysfunction in children turns out to be
      challenging due to low attention span, insufficient linguistic development and
      lack of odor experiences. Several smell tests have been developed for adults.
      Most of these examinations take a relatively long time and require a high level
      of concentration. Therefore, the aim of the current study was to evaluate an odor
      discrimination and olfactory threshold test using the frequently used "Sniffin'
      Sticks" in children and adolescents in a simplified two-alternative-forced-choice
      version (2AFC) and compare it to the original three-alternative-forced-choice
      test (3AFC). One-hundred-twenty-one healthy participants aged between 5 and 17
      years took part in this study. Within each of the two sessions participants
      underwent olfactory testing using the modified 2AFC as well as the standard 3AFC
      method. A better test-retest reliability was achieved using the original 3AFC
      method compared to the modified 2AFC. This was true for the odor discrimination
      as well as the olfactory threshold. Age had a significant influence on both
      tests, which should be considered when testing young children. We discuss these
      findings with relation to the existing norms and recommend using the 3AFC version
      due to a better test-retest reliability to measure olfactory function in
      children.

PMID- 28512303
TI  - Volunteer Participation in the Health eHeart Study: A Comparison with the US
      Population.
AB  - Direct volunteer "eCohort" recruitment can be an efficient way of recruiting
      large numbers of participants, but there is potential for volunteer bias. We
      compared self-selected participants in the Health eHeart Study to participants in
      the National Health And Nutrition Examination Survey (NHANES) 2013-14, a cross
      sectional survey of the US population. Compared with the US population
      (represented by 5,769 NHANES participants), the 12,280 Health eHeart participants
      with complete survey data were more likely to be female (adjusted odds ratio
      (ORadj) = 3.1; 95% confidence interval (CI) 2.9-3.5); less likely to be Black,
      Hispanic, or Asian versus White/non-Hispanic (ORadj's = 0.4-0.6, p < 0.01); more
      likely to be college-educated (ORadj = 15.8 (13-19) versus <=high school); more
      likely to have cardiovascular diseases and risk factors (ORadj's = 1.1-2.8, p <
      0.05) except diabetes (ORadj = 0.8 (0.7-0.9); more likely to be in excellent
      general health (ORadj = 0.6 (0.5-0.8) for "Good" versus "Excellent"); and less
      likely to be current smokers (ORadj = 0.3 (0.3-0.4)). While most self-selection
      patterns held for Health eHeart users of Bluetooth blood pressure cuff
      technology, there were some striking differences; for example, the gender ratio
      was reversed (ORadj = 0.6 (0.4-0.7) for female gender). Volunteer participation
      in this cardiovascular health-focused eCohort was not uniform among US adults nor
      for different components of the study.

PMID- 28512304
TI  - Nearly Perfect Durable Superhydrophobic Surfaces Fabricated by a Simple One-Step
      Plasma Treatment.
AB  - Fabrication of superhydrophobic surfaces is an area of great interest because it
      can be applicable to various engineering fields. A simple, safe and inexpensive
      fabrication process is required to fabricate applicable superhydrophobic
      surfaces. In this study, we developed a facile fabrication method of nearly
      perfect superhydrophobic surfaces through plasma treatment with argon and oxygen
      gases. A polytetrafluoroethylene (PTFE) sheet was selected as a substrate
      material. We optimized the fabrication parameters to produce superhydrophobic
      surfaces of superior performance using the Taguchi method. The contact angle of
      the pristine PTFE surface is approximately 111.0 degrees  +/- 2.4 degrees , with
      a sliding angle of 12.3 degrees  +/- 6.4 degrees . After the plasma treatment,
      nano-sized spherical tips, which looked like crown-structures, were created. This
      PTFE sheet exhibits the maximum contact angle of 178.9 degrees , with a sliding
      angle less than 1 degrees . As a result, this superhydrophobic surface requires a
      small external force to detach water droplets dripped on the surface. The contact
      angle of the fabricated superhydrophobic surface is almost retained, even after
      performing an air-aging test for 80 days and a droplet impacting test for 6 h.
      This fabrication method can provide superb superhydrophobic surface using simple
      one-step plasma etching.

PMID- 28512306
TI  - Structure Based docking studies towards exploring potential anti-androgen
      activity of selected phytochemicals against Prostate Cancer.
AB  - Prostate cancer (PCa) is the second most common malignancy amongst men worldwide.
      Under PCa maintenance therapy drugs acting as antagonists/partial agonists of
      hormone receptors against the prostate tissue are used in clinical practices.
      Prominent drugs being Cyproterone acetate, Flutamide, Bicalutamide, they not only
      cause acute and long-term toxicity, but also develops drug resistance among
      patients. Our focus has been on phytochemicals which do not exhibit any
      cytotoxicity and have significant androgen receptor (AR) inhibition activity. As
      Protein- Ligand interactions play a key role in structure based drug design, so
      by using molecular docking, we screened 803 phytochemicals and investigated their
      binding affinity against AR. The three dimensional (3D) structure of AR was
      retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 803
      phytochemicals using Argus Lab. Molecular docking and drug likeness studies were
      made using ADMET properties while Lipinski's rule of five was performed for the
      phytochemicals to evaluate their anti-prostate cancer activity. The results
      showed that Isobavachin exhibited best binding affinity of -13.73 kcal/mol with
      AR followed by Glabranin, Anthocyanin and Eriosemation. Our studies therefore
      reveal that these four phytochemicals could be promising candidates for further
      evaluation for PCa prevention or management.

PMID- 28512305
TI  - Mutation screening in genes known to be responsible for Retinitis Pigmentosa in
      98 Small Han Chinese Families.
AB  - Retinitis pigmentosa (RP) is highly heterogeneous in both clinical and genetic
      fields. Accurate mutation screening is very beneficial in improving clinical
      diagnosis and gene-specific treatment of RP patients. The reason for the
      difficulties in genetic diagnosis of RP is that the ethnic-specific mutation
      databases that contain both clinical and genetic information are largely
      insufficient. In this study, we recruited 98 small Han Chinese families
      clinically diagnosed as RP, including of 22 dominant, 19 recessive, 52 sporadic,
      and five X-linked. We then used whole exome sequencing (WES) analysis to detect
      mutations in the genes known for RP in 101 samples from these 98 families. In
      total, we identified 57 potential pathogenic mutations in 40 of the 98 (41%)
      families in 22 known RP genes, including 45 novel mutations. We detected
      mutations in 13 of the 22 (59%) typical autosomal dominant families, 8 of the 19
      (42%) typical autosomal recessive families, 16 of the 52 (31%) sporadic small
      families, and four of the five (80%) X-linked families. Our results extended the
      mutation spectrum of known RP genes in Han Chinese, thus making a contribution to
      RP gene diagnosis and the pathogenetic study of RP genes.

PMID- 28512307
TI  - Comparing the Success Rate of Dacryocystorhinostomy With and Without Silicone
      Intubation: A Trial Sequential Analysis of Randomized Control Trials.
AB  - A previous meta-analysis reported no benefit for silicone intubation during
      dacryocystorhinostomy. However, the power of this meta-analysis was 0.274.
      Therefore, the benefit of silicone intubation remains controversial. We undertook
      a cumulative meta-analysis to evaluate the success rate of dacryocystorhinostomy
      (DCR) with and without the use of a stent. Pubmed, EMBASE and the Cochrane
      Library were searched. Statistical power and trial sequential analyses were
      performed according to the result of the meta-analysis. Twelve randomized
      controlled trials involving 969 cases met the inclusion criteria. The success
      rates of DCR with and without intubation were significantly different (p =
      0.006). The success rates of external DCR (EX-DCR) with and without intubation
      were also significantly different based on subgroup analysis (p = 0.002). The
      cumulative z-curves crossed the O'Brian-Fleming boundaries. There were no
      significant differences in the success rate in the endonasal endoscopic DCR (EN
      DCR) subgroup or the occurrence of postoperative complications between the two
      groups based on the meta-analysis, and the z-curve did not intersect any trial
      sequential analysis boundaries. DCR with intubation achieved better results than
      DCR without intubation, especially in the EX-DCR subgroup. Differences in the
      success rate in the EN-DCR subgroup and postoperative complications between the
      two groups were underpowered to reach a conclusion.

PMID- 28512308
TI  - Quantum key distribution with hacking countermeasures and long term field trial.
AB  - Quantum key distribution's (QKD's) central and unique claim is information
      theoretic security. However there is an increasing understanding that the
      security of a QKD system relies not only on theoretical security proofs, but also
      on how closely the physical system matches the theoretical models and prevents
      attacks due to discrepancies. These side channel or hacking attacks exploit
      physical devices which do not necessarily behave precisely as the theory expects.
      As such there is a need for QKD systems to be demonstrated to provide security
      both in the theoretical and physical implementation. We report here a QKD system
      designed with this goal in mind, providing a more resilient target against
      possible hacking attacks including Trojan horse, detector blinding, phase
      randomisation and photon number splitting attacks. The QKD system was installed
      into a 45 km link of a metropolitan telecom network for a 2.5 month period,
      during which time the system operated continuously and distributed 1.33 Tbits of
      secure key data with a stable secure key rate over 200 kbit/s. In addition
      security is demonstrated against coherent attacks that are more general than the
      collective class of attacks usually considered.

PMID- 28512309
TI  - Triplet Cooper pairs induced in diffusive s-wave superconductors interfaced with
      strongly spin-polarized magnetic insulators or half-metallic ferromagnets.
AB  - Interfacing superconductors with strongly spin-polarized magnetic materials opens
      the possibility to discover new spintronic devices in which spin-triplet Cooper
      pairs play a key role. Motivated by the recent derivation of spin-polarized
      quasiclassical boundary conditions capable of describing such a scenario in the
      diffusive limit, we consider the emergent physics in hybrid structures comprised
      of a conventional s-wave superconductor (e.g. Nb, Al) and either strongly spin
      polarized ferromagnetic insulators (e.g. EuO, GdN) or halfmetallic ferromagnets
      (e.g. CrO2, LCMO). In contrast to most previous works, we focus on how the
      superconductor itself is influenced by the proximity effect, and how the
      generated triplet Cooper pairs manifest themselves in the self-consistently
      computed density of states (DOS) and the superconducting critical temperature T c
      . We provide a comprehensive treatment of how the superconductor and its
      properties are affected by the triplet pairs, demonstrating that our theory can
      reproduce the recent observation of an unusually large zero-energy peak in a
      superconductor interfaced with a half-metal, which even exceeds the normal-state
      DOS. We also discuss the recent observation of a large superconducting spin-valve
      effect with a T c change ~1 K in superconductor/half-metal structures, in which
      case our results indicate that the experiment cannot be explained fully by a long
      ranged triplet proximity effect.

PMID- 28512311
TI  - Dramatic improvement of strain hardening and ductility to 95% in highly
      deformable high-strength duplex lightweight steels.
AB  - Ferrite + austenite duplex lightweight steels have been actively developed by
      adding low-density Al for overcoming a limitation of stiffness deterioration by a
      traditional approach to obtain a weight reduction. Multiple-stage deformation
      mechanism in lightweight steels, i.e., simultaneous formation of deformation
      induced martensite and deformation twin and additional plasticity by twinning,
      has been nominated as an attractive strategy, but shows a steady flow behavior
      with early plastic instability. Here, we present a newly designed Fe-0.3C-9Mn-5Al
      steel in order to obtain an optimal level of stability of austenite and a
      resultant outstanding combination of tensile strength and ductility, e.g., 874
      MPa and 72%, together with sufficiently high strain hardening. These enhanced
      properties are attributed to the decreased austenite stability by controlling the
      austenite size and alloying partitioning due to variation in austenite fraction
      inside duplex microstructures. The present work gives a promise for structural
      applications requiring both reduced specific weight and remarkable deformability.

PMID- 28512310
TI  - FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.
AB  - Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets
      cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte
      growth and the development of left ventricular hypertrophy (LVH) in rodents.
      Serum FGF23 levels are highly elevated in patients with chronic kidney disease
      (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH
      and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23
      are solely pathological, or if they potentially can be reversed. Here, we report
      that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon
      removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates
      established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form
      of accelerated cardiovascular aging, we also studied age-related cardiac
      remodeling. We show that aging mice lacking FGFR4 are protected from LVH.
      Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of
      FGF23 on aortic relaxation do not require FGFR4. Taken together, our data
      highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling
      and function, and indicate that pharmacological interference with cardiac
      FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.

PMID- 28512312
TI  - Two-step phase shifting differential-recording digital holographic microscopy.
AB  - We present two-step phase-shifting differential-recording digital holographic
      microscopy (TPD-DH in microscopy) for phase imaging of microscopic transparent
      elements. Two CCDs are employed to record two interferograms at two different
      defocusing distances. The interferograms on the two CCD cameras are shifted for a
      phase retarder 0 and pi via an all-optics phase shifting unit. A novel algorithm
      is proposed to reconstruct both amplitude and phase distributions of the object
      wave from the recorded interferograms. This method has the same spectrum
      bandwidth and measurement accuracy with those of conventional four-step phase
      shifting interferometry (FS-PSI), whereas it reduces the measurement time by
      half.

PMID- 28512313
TI  - A Rapid Capillary-Pressure Driven Micro-Channel to Demonstrate Newtonian Fluid
      Behavior of Zebrafish Blood at High Shear Rates.
AB  - Blood viscosity provides the rheological basis to elucidate shear stress
      underlying developmental cardiac mechanics and physiology. Zebrafish is a high
      throughput model for developmental biology, forward-genetics, and drug discovery.
      The micro-scale posed an experimental challenge to measure blood viscosity. To
      address this challenge, a microfluidic viscometer driven by surface tension was
      developed to reduce the sample volume required (3MUL) for rapid (<2 min) and
      continuous viscosity measurement. By fitting the power-law fluid model to the
      travel distance of blood through the micro-channel as a function of time and
      channel configuration, the experimentally acquired blood viscosity was compared
      with a vacuum-driven capillary viscometer at high shear rates (>500 s-1), at
      which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a
      Newtonian fluid. The measured values of whole blood from the micro-channel
      (4.17cP) and the vacuum method (4.22cP) at 500 s-1 were closely correlated at 27 
      degrees C. A calibration curve was established for viscosity as a function of
      hematocrits to predict a rise and fall in viscosity during embryonic development.
      Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian
      fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity
      during development.

PMID- 28512314
TI  - Water-Assisted Synthesis of Molybdenum Disulfide Film with Single Organic Liquid
      Precursor.
AB  - We report on the synthesis of large-area molybdenum disulfide (MoS2) film on an
      insulating substrate by means of chemical vapor deposition. A single mixture of
      molybdenum hexacarbonyl (Mo(CO)6) and dimethyl disulfide (C2H6S2) was utilized as
      an organic liquid precursor for the synthesis of MoS2 film. Carbon impurities
      stemming from the dissociation of the organic precursor are effectively removed
      by water oxidation, and hydrogen gas, which is a by-product of the oxidation of
      carbon impurities, inhibits the formation of molybdenum oxides. The use of a
      liquid precursor assisted with water oxidation ensures high reproducibility and
      full-coverage of MoS2 film for large area, which is not typically achieved with
      solid precursors such as molybdenum oxide and sulfur powder. We believe that our
      approach will advance the synthesis of transition metal dichalcogenides.

PMID- 28512315
TI  - Midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible, and field
      caught populations of Plutella xylostella, and phenomics of the predominant
      midgut bacterium Enterococcus mundtii.
AB  - Gut bacteria play a significant role in host insect. This study evaluated detail
      difference of midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible
      and field-caught populations of diamondback moth, and studied phenomics of the
      predominant midgut bacterium Enterococcus mundtii. Cultivable bacteria revealed
      that E. mundtii and Carnobacterium maltaromaticum dominated the bacterial
      populations from deltamethrin-resistant and deltamethrin-susceptible larval
      midguts, whereas E. mundtii was predominant in field-caught population. Illumina
      sequencing analysis indicated that 97% of the midgut bacteria were from the phyla
      Firmicutes, Proteobacteria and Cyanobacteria. Both resistant and susceptible
      populations had more Enterococcus and Carnobacterium. Enterococcus,
      Carnobacterium, Bacillus, and Pseudomonas were predominant in the field-caught
      population. A phenomics analysis revealed that E. mundtii was able to metabolize
      25.26% of the tested carbon sources, 100% of the nitrogen sources, 100% of the
      phosphorus sources and 97.14% of the sulfur sources, had a wide range of
      osmolytes and pH conditions, and showed active deaminase activity but no
      decarboxylase activity. This is the first report regarding different populations
      of DBM midgut bacteria analyzed using both high-throughput DNA sequencing and
      cultivation methods, and also first report concerning the phenomics of E.
      mundtii. The phenomics of E. mundtii provide a basis for the future study of gut
      bacteria functions.

PMID- 28512316
TI  - Phenotypic plasticity, trade-offs and gene expression changes accompanying
      dietary restriction and switches in Bactrocera dorsalis (Hendel) (Diptera:
      Tephritidae).
AB  - In this study, we investigated the effects of dietary restriction (DR) and
      variable diets on phenotypes and gene expression in oriental fruit fly,
      Bactrocera dorsalis (Hendel), one of the most economically important pests in the
      family Tephritidae around the world. As expected, we found that DR altered the B.
      dorsalis phenotypes by significantly increasing stress resistance and lifespan,
      but reduced egg production when compared with the control diet. The results
      suggested a trade-off between reproduction versus somatic maintenance (stress
      resistance) and lifespan in B. dorsalis. Diet also had a significant effect on
      hatchability, and DR could increase the egg hatching success of B. dorsalis.
      Furthermore, DR up-regulated metabolic pathways involved in energy homeostasis
      and down-regulated pathways in egg production, which might mediate trade-offs
      between somatic maintenance and reproduction under DR regimes. The gene
      expression profiles in response to the acute dietary switches indicated that the
      digestive and metabolic pathways maybe involved in the adaptability of flies to
      variable dietary resources. In summary, the research facilitates a better
      understanding of the molecular mechanisms responsible for the B. dorsalis'
      phenotypic adjustments to the different qualities of the available diets.

PMID- 28512318
TI  - Structure-based prediction and identification of 4-epimerization activity of
      phosphate sugars in class II aldolases.
AB  - Sugar 4-epimerization reactions are important for the production of rare sugars
      and their derivatives, which have various potential industrial applications. For
      example, the production of tagatose, a functional sweetener, from fructose by
      sugar 4-epimerization is currently constrained because a fructose 4-epimerase
      does not exist in nature. We found that class II D-fructose-1,6-bisphosphate
      aldolase (FbaA) catalyzed the 4-epimerization of D-fructose-6-phosphate (F6P) to
      D-tagatose-6-phosphate (T6P) based on the prediction via structural comparisons
      with epimerase and molecular docking and the identification of the condensed
      products of C3 sugars. In vivo, the 4-epimerization activity of FbaA is normally
      repressed. This can be explained by our results showing the catalytic efficiency
      of D-fructose-6-phosphate kinase for F6P phosphorylation was significantly higher
      than that of FbaA for F6P epimerization. Here, we identified the epimerization
      reactions and the responsible catalytic residues through observation of the
      reactions of FbaA and L-rhamnulose-1-phosphate aldolases (RhaD) variants with
      substituted catalytic residues using different substrates. Moreover, we obtained
      detailed potential epimerization reaction mechanism of FbaA and a general
      epimerization mechanism of the class II aldolases L-fuculose-1-phosphate
      aldolase, RhaD, and FbaA. Thus, class II aldolases can be used as 4-epimerases
      for the stereo-selective synthesis of valuable carbohydrates.

PMID- 28512317
TI  - Structural determinants of Neosartorya fischeri antifungal protein (NFAP) for
      folding, stability and antifungal activity.
AB  - The recent global challenges to prevent and treat fungal infections strongly
      demand for the development of new antifungal strategies. The structurally very
      similar cysteine-rich antifungal proteins from ascomycetes provide a feasible
      basis for designing new antifungal molecules. The main structural elements
      responsible for folding, stability and antifungal activity are not fully
      understood, although this is an essential prerequisite for rational protein
      design. In this study, we used the Neosartorya fischeri antifungal protein (NFAP)
      to investigate the role of the disulphide bridges, the hydrophobic core, and the
      N-terminal amino acids in the formation of a highly stable, folded, and
      antifungal active protein. NFAP and its mutants carrying cysteine deletion
      (NFAPDeltaC), hydrophobic core deletion (NFAPDeltah), and N-terminal amino acids
      exchanges (NFAPDeltaN) were produced in Pichia pastoris. The recombinant NFAP
      showed the same features in structure, folding, stability and activity as the
      native protein. The data acquired with mass spectrometry, structural analyses and
      antifungal activity assays of NFAP and its mutants proved the importance of the
      disulphide bonding, the hydrophobic core and the correct N-terminus for folding,
      stability and full antifungal function. Our findings provide further support to
      the comprehensive understanding of the structure-function relationship in members
      of this protein group.

PMID- 28512319
TI  - What the skull and scapular morphology of the dugong (Dugong dugon) can tell us:
      sex, habitat and body length?
AB  - The dugong (Dugong dugon, Muller) is an endangered marine mammal species. We
      examined the relationship between sex, habitat and body length based on the skull
      and scapular morphology and morphometrics of 81 dugong samples in Thailand. A
      total of 58 parameters from the skull and scapula (25 from the cranium, 23 from
      the mandible and 10 from the scapula) as well as tusks were used in this study.
      Data were analyzed by univariate analysis, followed by discriminant analysis and
      multivariate linear regression. Here we show, 100% and 98.5% accuracy rates for
      sexing using large tusks and the skull, respectively. Scapular morphology using
      the caudal border tubercle and coracoid process showed 91.30% and 96.15% accuracy
      rates for identifying males and females. Skull morphometrics could categorize
      dugong habitat, i.e. living in the Andaman Sea or Gulf of Thailand, with 100%
      accuracy. Moreover, our model could be used to estimate body length with
      coefficient of determination (R 2) of 0.985. The results of our study showed that
      skull morphology and morphometric measurements could be used as a tool for sex
      identification, location identification and estimation of body length. But
      scapular morphology is the best tool for sex identification in dugongs.

PMID- 28512320
TI  - Hyponatremia upon presentation to the emergency department - the need for urgent
      neuroimaging studies.
AB  - This study aims to evaluate the necessity of urgent neuroimaging for emergency
      admissions exhibiting symptomatology of profound hyponatremia. We retrospectively
      analyzed the medical records of all patients admitted to the emergency room of
      the University Hospital Munster from 2010 to 2014 with a serum sodium value < 125
      mmol/L. From 52918 emergency admissions, 261 patients with profound hyponatremia
      were identified, of whom 140 (54%) had neurological symptoms. Unspecific weakness
      and confusion were the most prevalent of these symptoms (59%). Focal neurological
      signs [FNS] were present in 31% of cases and neuroimaging was performed in 68%
      (95/140) of symptomatic patients. Multiple logistic regression analysis
      identified FNS, seizures, altered consciousness and age as independent predictors
      for conducting neuroimaging (all p < 0.05). Significant pathological findings
      consistent with acute symptomatology were evident in 17 cases, all of whom had
      FNS. Recursive partitioning analyses confirmed FNS as the best predictor of
      neuroimaging pathology (p < 0.001). Absence of FNS had a negative predictive
      value of 100% [95% confidence interval: 93-100%] for excluding neuroimaging
      pathology. In conclusion, emergency patients with profound hyponatremia
      frequently show nonspecific-neurological symptoms and may undergo neuroimaging
      unnecessarily. The lack of FNS may serve as a valuable criterion for withholding
      neuroimaging until hyponatremia has been corrected.

PMID- 28512321
TI  - Restoration of the growth of Escherichia coli under K+-deficient conditions by
      Cs+ incorporation via the K+ transporter Kup.
AB  - Biological incorporation of cesium ions (Cs+) has recently attracted significant
      attention in terms of the possible applications for bioremediation of radiocesium
      and their significant roles in biogeochemical cycling. Although high
      concentrations of Cs+ exhibit cytotoxicity on microorganisms, there are a few
      reports on the promotive effects of Cs+ on microbial growth under K+-deficient
      conditions. However, whether this growth-promoting effect is a common phenomenon
      remains uncertain, and direct correlation between growth promotion and Cs+ uptake
      abilities has not been confirmed yet. Here, we validated the growth promotive
      effects of Cs+ uptake under K+-deficient conditions using an Escherichia coli
      strain with an inducible expression of the Kup K+ transporter that has
      nonspecific Cs+ transport activities (strain kup-IE). The strain kup-IE exhibited
      superior growth under the Cs+-supplemented and K+-deficient conditions compared
      to the wild type and the kup null strains. The intracellular Cs+ levels were
      significantly higher in strain kup-IE than in the other strains, and were well
      correlated with their growth yields. Furthermore, induction levels of the kup
      gene, intracellular Cs+ concentrations, and the growth stimulation by Cs+ also
      correlated positively. These results clearly demonstrated that Cs+ incorporation
      via Kup transporter restores growth defects of E. coli under K+-deficient
      conditions.

PMID- 28512323
TI  - Nicotine in floral nectar pharmacologically influences bumblebee learning of
      floral features.
AB  - Many plants defend themselves against herbivores by chemical deterrents in their
      tissues and the presence of such substances in floral nectar means that
      pollinators often encounter them when foraging. The effect of such substances on
      the foraging behaviour of pollinators is poorly understood. Using artificial
      flowers in tightly-controlled laboratory settings, we examined the effects of the
      alkaloid nicotine on bumblebee foraging performance. We found that bumblebees
      confronted simultaneously with two equally rewarded nicotine-containing and
      nicotine-free flower types are deterred only by unnaturally high nicotine
      concentrations. This deterrence disappears or even turns into attraction at lower
      nectar-relevant concentrations. The alkaloid has profound effects on learning in
      a dose-dependent manner. At a high natural dose, bees learn the colour of a
      nicotine-containing flower type more swiftly than a flower type with the same
      caloric value but without nicotine. Furthermore, after experiencing flowers
      containing nicotine in any tested concentration, increasing numbers of bumblebees
      stay more faithful to these flowers, even if they become a suboptimal choice in
      terms of reward. These results demonstrate that alkaloids enhance pollinator
      flower constancy, opening new perspectives in co-evolutionary process between
      plants and pollinators.

PMID- 28512325
TI  - Complex hierarchical microstructures of Cambrian mollusk Pelagiella: insight into
      early biomineralization and evolution.
AB  - Shell microstructure and mineralogy of Pelagiella madianensis Zhou & Xiao, 1984,
      a globally distributed Cambrian micromollusk, are investigated based on abundant
      and extraordinarily well-preserved specimens from Xinji Formation, Longxian,
      Shaanxi, North China. Five types of aragonitic microstructures have been
      recognized. The lamello-fibrillar microstructure, previously known from
      Pelagiella, constructs the outermost shell layer, while the remaining four types
      are reported here for the first time in this genus. They include fibrous
      foliated, foliated aragonite, crossed foliated lamellar and isolated tablets. The
      animal constructs these five types of microstructures to build its shell in a
      complex hierarchical pattern with four orders: crystallite columns, laths, folia
      and lamellae. These findings demonstrate that the capability of building complex
      shell microstructures had already evolved by the Cambrian explosion. In addition,
      this work shows that early aragonitic shells were constructed with fibers, laths,
      folia and isolated tablets, indicating increased controls over biomineralization
      by the animal.

PMID- 28512324
TI  - Global gene expression analysis provides insight into local adaptation to
      geothermal streams in tadpoles of the Andean toad Rhinella spinulosa.
AB  - The anuran Rhinella spinulosa is distributed along the Andes Range at altitudes
      that undergo wide daily and seasonal variation in temperature. One of the
      populations inhabits geothermal streams, a stable environment that influences
      life history traits such as the timing of metamorphosis. To investigate whether
      this population has undergone local adaptation to this unique habitat, we carried
      out transcriptome analyses in animals from two localities in two developmental
      stages (prometamorphic and metamorphic) and exposed them to two temperatures (20
      and 25  degrees C). RNA-Seq, de novo assembly and annotation defined a
      transcriptome revealing 194,469 high quality SNPs, with 1,507 genes under
      positive selection. Comparisons among the experimental conditions yielded 1,593
      differentially expressed genes. A bioinformatics search for candidates revealed a
      total of 70 genes that are highly likely to be implicated in the adaptive
      response of the population living in a stable environment, compared to those
      living in an environment with variable temperatures. Most importantly, the
      population inhabiting the geothermal environment showed decreased transcriptional
      plasticity and reduced genetic variation compared to its counterpart from the non
      stable environment. This analysis will help to advance the understanding of the
      molecular mechanisms that account for the local adaptation to geothermal streams
      in anurans.

PMID- 28512322
TI  - Physicochemical properties of dietary phytochemicals can predict their passive
      absorption in the human small intestine.
AB  - A diet high in phytochemical-rich plant foods is associated with reducing the
      risk of chronic diseases such as cardiovascular and neurodegenerative diseases,
      obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the
      common component underlying these chronic diseases. Whilst the positive health
      effects of phytochemicals and their metabolites have been demonstrated to
      regulate OSI, the timing and absorption for best effect is not well understood.
      We developed a model to predict the time to achieve maximal plasma concentration
      (Tmax) of phytochemicals in fruits and vegetables. We used a training dataset
      containing 67 dietary phytochemicals from 31 clinical studies to develop the
      model and validated the model using three independent datasets comprising a total
      of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed
      model based on dietary intake forms and the physicochemical properties
      lipophilicity and molecular mass accurately predicts Tmax of dietary
      phytochemicals and pharmaceutical compounds over a broad range of chemical
      classes. This is the first direct model to predict Tmax of dietary phytochemicals
      in the human body. The model informs the clinical dosing frequency for optimising
      uptake and sustained presence of dietary phytochemicals in circulation, to
      maximise their bio-efficacy for positively affect human health and managing OSI
      in chronic diseases.

PMID- 28512327
TI  - Prognostic value of hypoalbuminemia for adverse outcomes in patients with
      rheumatic heart disease undergoing valve replacement surgery.
AB  - High-risk patients with rheumatic heart disease (RHD) who were undergoing valve
      replacement surgery (VRS) were not identified entirely. This study included 1782
      consecutive patients with RHD who were undergoing VRS to explore the relationship
      between hypoalbuminemia and adverse outcomes and to confirm whether
      hypoalbuminemia plays a role in risk evaluation. A total of 27.3% of the RHD
      patients had hypoalbuminemia. In-hospital deaths were significantly higher in the
      hypoalbuminemic group than in the non-hypoalbuminemic group (6.6% vs 3.1%, P =
      0.001). Hypoalbuminemia was an independent predictor of in-hospital death (OR =
      1.89, P = 0.014), even after adjusting for the Euro score. The addition of
      hypoalbuminemia to Euro score enhanced net reclassification improvement (0.346
      for in-hospital death, P = 0.004; 0.306 for 1-year death, p = 0.005). A Kaplan
      Meier curve analysis revealed that the cumulative rate of 1-year mortality after
      the operation was higher in patients with a new Euro score >=6. These findings
      indicated that hypoalbuminemia was an independent risk factor for in-hospital and
      1-year mortality after VRS in patients with RHD, which might have additive
      prognostic value to Euro score.

PMID- 28512326
TI  - Accuracy of shear wave elastography for the diagnosis of prostate cancer: A meta
      analysis.
AB  - Many studies have established the high diagnostic accuracy of shear wave
      elastography (SWE) for the detection of prostate cancer (PCa); however, its
      utility remains a subject of debate. This meta-analysis sought to appraise the
      overall accuracy of SWE for the detection of PCa. A literature search of the
      PubMed, Embase, Cochrane Library, Web of Science and CNKI (China National
      Knowledge Infrastructure) databases was conducted. In all of the included
      studies, the diagnostic accuracy of SWE was compared with that of histopathology,
      which was used as a standard. Data were pooled, and the sensitivity, specificity,
      area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood
      ratio (NLR), and diagnostic odds ratio (DOR) were calculated to estimate the
      accuracy of SWE. The pooled sensitivity and specificity for the diagnosis of PCa
      by SWE were 0.844 (95% confidence interval: 0.696-0.927) and 0.860 (0.792-0.908),
      respectively. The AUC was 0.91 (0.89-0.94), the PLR was 6.017 (3.674-9.853), and
      the NLR was 0.182 (0.085-0.389). The DOR was 33.069 (10.222-106.982). Thus, SWE
      exhibited high accuracy for the detection of PCa using histopathology as a
      diagnostic standard. Moreover, SWE may reduce the number of core biopsies needed.

PMID- 28512328
TI  - Tacrolimus Blood Level Fluctuation Predisposes to Coexisting BK Virus Nephropathy
      and Acute Allograft Rejection.
AB  - BK virus nephropathy (BKVN) and allograft rejection are two distinct disease
      entities which occur at opposite ends of the immune spectrum. However, they
      coexist in renal transplant recipients. Predisposing factors for this coexistence
      remain elusive. We identified nine biopsy-proven BKVN patients with coexisting
      acute rejection, and 21 patients with BKVN alone. We retrospectively analyzed the
      dosage and blood concentrations of immunosuppressants during the 3-month period
      prior to the renal biopsy between the two patient groups. Compared to the BKVN
      alone group, renal function was noticeably worse in the coexistence group (p =
      0.030). Regarding the dose and average drug level of immunosuppressants, there
      was no difference between the two groups. Interestingly, the coefficient of
      variance of tacrolimus trough blood level was noticeably higher during the 3
      month period prior to the renal biopsy in the coexistence group (p = 0.010). Our
      novel findings suggest that a higher variability of tacrolimus trough level may
      be associated with the coexistence of BKVN and acute rejection. Since the
      prognosis is poor and the treatment is challenging in patients with coexisting
      BKVN and acute rejection, transplant clinicians should strive to avoid
      fluctuations in immunosuppressant drug levels in patients with either one of
      these two disease entities.

PMID- 28512329
TI  - Tree-ring widths are good proxies of annual variation in forest productivity in
      temperate forests.
AB  - Tree rings have long been used to calibrate the net primary production (NPP) time
      series predicted by process-based models, based on an implicit assumption that
      ring-width indices (RWI) can well reflect temporal NPP change. However, this
      assumption has seldom been tested systematically. In this study, 36 plots were
      set in three forest types from four sites along a latitudinal gradient in
      northeast China. For each plot, we constructed chronologies and stand NPP of the
      past 20 years to examine: is RWI a good proxy of inter-annual variation of forest
      NPP for different forest types under different climate? If it is, why? Our
      results indicate that RWI was closely related to stand NPP in most cases, and
      could be used as a good proxy of NPP in temperate forests. Standard and arstan
      chronologies were better related to NPP series than residual chronology. Stand
      NPP time-series were mainly determined by large trees, and the correlation
      between RWI and NPP was also higher for larger trees. We suggest that large trees
      and dominant species of canopy layer should be sampled for chronology
      construction. Large trees are major contributors of forest biomass and
      productivity, and should have priority in forest conservation in a rapid-warming
      world.

PMID- 28512330
TI  - Direct evaluation of influence of electron damage on the subcell performance in
      triple-junction solar cells using photoluminescence decays.
AB  - Tandem solar cells are suited for space applications due to their high
      performance, but also have to be designed in such a way to minimize influence of
      degradation by the high energy particle flux in space. The analysis of the
      subcell performance is crucial to understand the device physics and achieve
      optimized designs of tandem solar cells. Here, the radiation-induced damage of
      inverted grown InGaP/GaAs/InGaAs triple-junction solar cells for various electron
      fluences are characterized using conventional current-voltage (I-V) measurements
      and time-resolved photoluminescence (PL). The conversion efficiencies of the
      entire device before and after damage are measured with I-V curves and compared
      with the efficiencies predicted from the time-resolved method. Using the time
      resolved data the change in the carrier dynamics in the subcells can be
      discussed. Our optical method allows to predict the absolute electrical
      conversion efficiency of the device with an accuracy of better than 5%. While
      both InGaP and GaAs subcells suffered from significant material degradation, the
      performance loss of the total device can be completely ascribed to the damage in
      the GaAs subcell. This points out the importance of high internal electric fields
      at the operating point.

PMID- 28512331
TI  - Entanglement concentration for arbitrary four-particle linear cluster states.
AB  - Cluster states, whose model are a remarkably rich structure in measurement-based
      quantum computation, hold high degree of entanglement, while entanglement is very
      fragile during the process of transmission because of the inevitable interaction
      with the environment. We propose two entanglement concentration protocols for
      four-particle linear cluster states which and are susceptible to the decoherence
      and the imperfect communication setups. In the first protocol, POVM operators are
      introduced to maximize the success probability, and the second protocol is based
      on cross-Kerr nonlinearity which is utilized to check the parity between the
      original particle and the ancillary particle. Both of the protocols have their
      own advantages. The first one can be easily realized in experiment by linear
      optics, while the one with cross-Kerr nonlinearity reach more than 90% success
      probability by iteration. Since the wide application of cluster states, the two
      protocols are efficient and valuable to different fields of quantum
      communication.

PMID- 28512332
TI  - Microalgal diversity fosters stable biomass productivity in open ponds treating
      wastewater.
AB  - It is established that biodiversity determines productivity of natural ecosystems
      globally. We have proved that abiotic factors influenced biomass productivity in
      engineered ecosystems i.e. high rate algal ponds (HRAPs), previously. This study
      demonstrates that biotic factors, particularly microalgal diversity, play an
      essential role in maintaining stable biomass productivity in HRAP treating
      municipal wastewater by mutualistic adaptation to environmental factors. The
      current study examined data from the second year of a two-year study on HRAP
      treating municipal wastewater. Microalgal diversity, wastewater characteristics,
      treatment efficiency and several environmental and meteorological factors were
      documented. Multivariate statistical analyses reveal that microalgae in
      uncontrolled HRAPs adapt to adverse environmental conditions by fostering
      diversity. Subsequently, five dominant microalgal strains by biovolume were
      isolated, enriched, and optimum conditions for high biomass productivity were
      ascertained. These laboratory experiments revealed that different microalgal
      strains dominate in different conditions and a consortium of these diverse taxa
      help in sustaining the algae community from environmental and predatory
      pressures. Diversity, niche or seasonal partitioning and mutualistic growth are
      pertinent in microalgal cultivation or wastewater treatment. Therefore,
      enrichment of selective species would deprive the collective adaptive ability of
      the consortium and encourage system vulnerability especially in wastewater
      treatment.

PMID- 28512333
TI  - Hybrid Organic Tandem Solar Cell Comprising Small-Molecule Bottom and
      Polymer:Fullerene Top Subcells Fabricated by Thin-Film Transfer.
AB  - Multilayer structures involving solution-deposited polymer films are difficult to
      fabricate, not allowing for unrestricted designs of polymer-based optoelectronic
      devices required for maximizing their performance. Here, we fabricate a hybrid
      organic tandem solar cell whose top and bottom subcells have polymer:fullerene
      and small molecules active layers, respectively, by a solvent-free process based
      on transferring the polymer:fullerene layer from an elastomeric stamp onto a
      vacuum-deposited bottom subcell. The interface between small-molecule and
      transferred polymer:fullerene layers is void-free at the nanoscale, allowing for
      efficient charge transport across the interface. Consequently, the transfer
      fabricated tandem cell has an open-circuit voltage (V OC) almost identical to the
      sum of V OC values for the single-junction devices. The short-circuit current
      density (J SC) of the tandem cell is maximized by current matching achieved by
      varying the thickness of the small-molecule active layer in the bottom subcell,
      which is verified by numerical simulations. The optimized transfer-fabricated
      tandem cell, whose active layers are composed of poly[2,1,3-benzothiadiazole-4,7
      diyl[4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b']dithiophene-2,6
      diyl]]:[6,6]-Phenyl-C71-butyric acid methyl ester and Di-[4-(N,N-di-p-tolyl
      amino)-phenyl]cyclohexane:C70, has V OC = 1.46 V, J SC = 8.48 mA/cm2, a fill
      factor of 0.51, leading to the power-conversion efficiency of 6.26%, the highest
      among small molecule-polymer:fullerene hybrid tandem solar cells demonstrated so
      far.

PMID- 28512334
TI  - Three-dimensional scoring of zebrafish behavior unveils biological phenomena
      hidden by two-dimensional analyses.
AB  - The study of zebrafish behavior represents a cornerstone upon which basic
      researchers promise to advance knowledge in life sciences. Although zebrafish
      swim in a three-dimensional (3D) space, their behavior in the lab is almost
      exclusively scored in two dimensions, whereby zebrafish are recorded using a
      single camera providing 2D videos. Whether this dimensional reduction preserves
      the reliability of data has not been addressed. Here we show that, compared to a
      3D observation, 2D data are flawed by over-reporting and under-reporting of
      locomotory differences. Specifically, we first reconstructed 3D trajectories
      through the integration of synchronous information derived from two cameras, and
      then compared them with the original 2D views in classical experimental paradigms
      assessing shoaling tendency, fear, anxiety, and general locomotion. Our results
      suggest that traditional behavioral scoring of individual zebrafish performed in
      2D may undermine data integrity, thereby requiring a general reconsideration of
      scoring zebrafish behavior to incorporate a 3D approach. We then demonstrate
      that, compared to 2D, a 3D approach requires a reduced number of subjects to
      achieve the same degree of validity. We anticipate these findings to largely
      benefit animal welfare by reducing the number of experimental subjects, without
      affecting statistical power.

PMID- 28512335
TI  - Arginine-rich cell-penetrating peptide-modified extracellular vesicles for active
      macropinocytosis induction and efficient intracellular delivery.
AB  - Extracellular vesicles (EVs) including exosomes have been shown to play crucial
      roles in cell-to-cell communication because of their ability to carry
      biofunctional molecules (e.g., microRNAs and enzymes). EVs also have
      pharmaceutical advantages and are highly anticipated to be a next-generation
      intracellular delivery tool. Here, we demonstrate an experimental technique that
      uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active
      macropinocytosis for effective cellular EV uptake. Modification of arginine-rich
      CPPs on the EV membrane resulted in the activation of the macropinocytosis
      pathway, and the number of arginine residues in the peptide sequences affected
      the cellular EV uptake efficiency. Consequently, the ribosome-inactivating
      protein saporin-encapsulated EVs modified with hexadeca-arginine (R16) peptide
      effectively attained anti-cancer activity.

PMID- 28512337
TI  - Powder Metallurgy Processing of a WxTaTiVCr High-Entropy Alloy and Its Derivative
      Alloys for Fusion Material Applications.
AB  - The WxTaTiVCr high-entropy alloy with 32at.% of tungsten (W) and its derivative
      alloys with 42 to 90at.% of W with in-situ TiC were prepared via the mixing of
      elemental W, Ta, Ti, V and Cr powders followed by spark plasma sintering for the
      development of reduced-activation alloys for fusion plasma-facing materials.
      Characterization of the sintered samples revealed a BCC lattice and a multi-phase
      structure. The selected-area diffraction patterns confirmed the formation of TiC
      in the high-entropy alloy and its derivative alloys. It revealed the development
      of C15 (cubic) Laves phases as well in alloys with 71 to 90at.% W. A mechanical
      examination of the samples revealed a more than twofold improvement in the
      hardness and strength due to solid-solution strengthening and dispersion
      strengthening. This study explored the potential of powder metallurgy processing
      for the fabrication of a high-entropy alloy and other derived compositions with
      enhanced hardness and strength.

PMID- 28512336
TI  - Lung Cancer Screening Based on Type-different Sensor Arrays.
AB  - In recent years, electronic nose (e-nose) systems have become a focus method for
      diagnosing pulmonary diseases such as lung cancer. However, principles and
      patterns of sensor responses in traditional e-nose systems are relatively
      homogeneous. Less study has been focused on type-different sensor arrays. In this
      paper, we designed a miniature e-nose system using 14 gas sensors of four types
      and its subsequent analysis of 52 breath samples. To investigate the performance
      of this system in identifying and distinguishing lung cancer from other
      respiratory diseases and healthy controls, five feature extraction algorithms and
      two classifiers were adopted. Lastly, the influence of type-different sensors on
      the identification ability of e-nose systems was analyzed. Results indicate that
      when using the LDA fuzzy 5-NN classification method, the sensitivity, specificity
      and accuracy of discriminating lung cancer patients from healthy controls with e
      nose systems are 91.58%, 91.72% and 91.59%, respectively. Our findings also
      suggest that type-different sensors could significantly increase the diagnostic
      accuracy of e-nose systems. These results showed e-nose system proposed in this
      study was potentially practicable in lung cancer screening with a favorable
      performance. In addition, it is important for type-different sensors to be
      considered when developing e-nose systems.

PMID- 28512339
TI  - Nash Equilibrium of Social-Learning Agents in a Restless Multiarmed Bandit Game.
AB  - We study a simple model for social-learning agents in a restless multiarmed
      bandit (rMAB). The bandit has one good arm that changes to a bad one with a
      certain probability. Each agent stochastically selects one of the two methods,
      random search (individual learning) or copying information from other agents
      (social learning), using which he/she seeks the good arm. Fitness of an agent is
      the probability to know the good arm in the steady state of the agent system. In
      this model, we explicitly construct the unique Nash equilibrium state and show
      that the corresponding strategy for each agent is an evolutionarily stable
      strategy (ESS) in the sense of Thomas. It is shown that the fitness of an agent
      with ESS is superior to that of an asocial learner when the success probability
      of social learning is greater than a threshold determined from the probability of
      success of individual learning, the probability of change of state of the rMAB,
      and the number of agents. The ESS Nash equilibrium is a solution to Rogers'
      paradox.

PMID- 28512338
TI  - Impact of metabolic status on the incidence of psoriasis: a Korean nationwide
      cohort study.
AB  - Growing evidence suggests that obesity is a risk factor for incident psoriasis.
      This study was aimed to evaluate the association of obesity and metabolic status
      with the incidence of psoriasis. A total of 418,057 adults were followed-up using
      a nationwide prospective cohort study in Korea. Participants were stratified
      based on the body mass index categories and metabolic condition. During the
      follow-up visit, 11054 (2.6%) cases were found to have psoriasis. Diabetes,
      hypertension, hyperlipidemia, and obesity were all found to be risk factors for
      incident psoriasis. The metabolically unhealthy non-obese (MUNO) subjects (hazard
      ratio [HR], 1.29; 95% confidence interval [CI], 1.22-1.37) and metabolically
      unhealthy obese subjects (MUO; HR, 1.33; 95% CI, 1. 26-1.41) had a significantly
      higher risk of psoriasis incidence as compared to metabolically healthy non-obese
      subjects. The risk of psoriasis development was found to be high among the MUNO
      and MUO subjects in both sexes and all age groups. In conclusion, the metabolic
      health status was significantly associated with an increased risk of psoriasis in
      both obese and non-obese individuals. However, further studies are needed to
      evaluate whether the control of metabolic parameters can lower the incidence of
      psoriasis.

PMID- 28512340
TI  - Using an Event-History with Risk-Free Model to Study the Genetics of Alcoholism.
AB  - Case-control genetic association studies typically ignore possible later disease
      onset in currently healthy subjects and assume that subjects with diseases
      equally contribute to the likelihood for inference, regardless of their onset
      age. Therefore, we used an event-history with risk-free model to simultaneously
      characterize alcoholism susceptibility and onset age in 65 independent non
      Hispanic Caucasian males in the Collaborative Study on the Genetics of
      Alcoholism. Following data quality control, we analysed 22 single nucleotide
      polymorphisms (SNPs) on 12 candidate genes. The single-SNP analysis showed that
      the dominant minor allele of rs2134655 on DRD3 increases alcoholism
      susceptibility; the dominant minor allele of rs1439047 on NTRK2 delays the
      alcoholism onset age, but the additive minor allele of rs172677 on GRIN2B and the
      dominant minor allele of rs63319 on ALDH1A1 advance the alcoholism onset age; and
      the dominant minor allele of rs1079597 on DRD2 shortens the onset age range.
      Similarly, multiple-SNPs analysis revealed joint effects of rs2134655, rs172677
      and rs1079597, with an adjustment for habitual smoking. This study provides a
      more comprehensive understanding of the genetics of alcoholism than previous case
      control studies.

PMID- 28512341
TI  - A new paradigm in sweat based wearable diagnostics biosensors using Room
      Temperature Ionic Liquids (RTILs).
AB  - Successful commercialization of wearable diagnostic sensors necessitates
      stability in detection of analytes over prolonged and continuous exposure to
      sweat. Challenges are primarily in ensuring target disease specific small
      analytes (i.e. metabolites, proteins, etc.) stability in complex sweat buffer
      with varying pH levels and composition over time. We present a facile approach to
      address these challenges using RTILs with antibody functionalized sensors on
      nanoporous, flexible polymer membranes. Temporal studies were performed using
      both infrared spectroscopic, dynamic light scattering, and impedimetric
      spectroscopy to demonstrate stability in detection of analytes, Interleukin-6 (IL
      6) and Cortisol, from human sweat in RTILs. Temporal stability in sensor
      performance was performed as follows: (a) detection of target analytes after 0,
      24, 48, 96, and 168 hours post-antibody sensor functionalization; and (b)
      continuous detection of target analytes post-antibody sensor functionalization.
      Limit of detection of IL-6 in human sweat was 0.2 pg/mL for 0-24 hours and 2
      pg/mL for 24-48 hours post-antibody sensor functionalization. Continuous
      detection of IL-6 over 0.2-200 pg/mL in human sweat was demonstrated for a period
      of 10 hours post-antibody sensor functionalization. Furthermore, combinatorial
      detection of IL-6 and Cortisol in human sweat was established with minimal cross
      talk for 0-48 hours post-antibody sensor functionalization.

PMID- 28512342
TI  - A gas sensor array for the simultaneous detection of multiple VOCs.
AB  - Air quality around the globe is declining and public health is seriously
      threatened by indoor air pollution. Typically, indoor air pollutants are composed
      of a series of volatile organic compounds (VOCs) that are generally harmful to
      the human body, especially VOCs with low molecular weights (less than 100 Da).
      Moreover, in some situations, more than one type of VOC is present; thus, a
      device that can detect one or more VOCs simultaneously would be most beneficial.
      Here, we synthesized a sensor array with 4 units to detect 4 VOCs: acetone (unit
      1), benzene (unit 2), methanol (unit 3) and formaldehyde (unit 4) simultaneously.
      All units were simultaneously exposed to 2.5 ppm of all four VOCs. The
      sensitivity of unit 1 was 14.67 for acetone and less than 2.54 for the other
      VOCs. The sensitivities of units 2, 3 and 4 to benzene, methanol and formaldehyde
      were 2 18.64, 20.98 and 17.26, respectively, and less than 4.01 for the other
      VOCs. These results indicated that the sensor array exhibited good selectivity
      and could be used for the real-time monitoring of indoor air quality. Thus, this
      device will be useful in situations requiring the simultaneous detection of
      multiple VOCs.

PMID- 28512343
TI  - The influence of statistical properties of Fourier coefficients on random
      Gaussian surfaces.
AB  - Many examples of natural systems can be described by random Gaussian surfaces.
      Much can be learned by analyzing the Fourier expansion of the surfaces, from
      which it is possible to determine the corresponding Hurst exponent and
      consequently establish the presence of scale invariance. We show that this
      symmetry is not affected by the distribution of the modulus of the Fourier
      coefficients. Furthermore, we investigate the role of the Fourier phases of
      random surfaces. In particular, we show how the surface is affected by a non
      uniform distribution of phases.

PMID- 28512344
TI  - Ecological relevance of skeletal fatty acid concentration and composition in
      Mediterranean scleractinian corals.
AB  - The intra-skeletal fatty acid concentration and composition of four Mediterranean
      coral species, namely Cladocora caespitosa, Balanophyllia europaea, Astroides
      calycularis and Leptopsammia pruvoti, were examined in young and old individuals
      living in three different locations of the Mediterranean Sea. These species are
      characterized by diverse levels of organization (solitary or colonial) and
      trophic strategies (symbiotic or non-symbiotic). Fatty acids have manifold
      fundamental roles comprehensive of membrane structure fluidity, cell signaling
      and energy storage. For all species, except for B. europaea, the intra-skeletal
      fatty acid concentration was significantly higher in young individuals than in
      old ones. Moreover, fatty acid concentration was higher in colonial corals than
      in solitary ones and in the symbiotic corals compared to non-symbiotic ones.
      Analysis by gas chromatography-mass spectrometry (GC-MS) revealed that palmitic
      acid (16:0) was the most abundant fatty acid, followed by stearic (18:0) in order
      of concentration. Oleic acid (18:1) was detected as the third main component only
      in skeletons from symbiotic corals. These results suggest that, in the limits of
      the studied species, intra-skeletal fatty acid composition and concentration may
      be used for specific cases as a proxy of level of organization and trophic
      strategy, and eventually coral age.

PMID- 28512345
TI  - Phosphoproteome Analysis Reveals Phosphorylation Underpinnings in the Brains of
      Nurse and Forager Honeybees (Apis mellifera).
AB  - The honeybee brain is a central organ in regulating wide ranges of honeybee
      biology, including life transition from nurse to forager bees. Knowledge is still
      lacking on how protein phosphorylation governs the neural activity to drive the
      age-specific labor division. The cerebral phosphoproteome of nurse and forager
      honeybees was characterized using Ti4+-IMAC phosphopeptide enrichment mass
      spectrometry-based proteomics and protein kinases (PKs) were predicted. There
      were 3,077 phosphosites residing on 3,234 phosphopeptides from 1004
      phosphoproteins in the nurse bees. For foragers the numbers were 3,056, 3,110,
      and 958, respectively. Notably, among the total 231 PKs in honeybee proteome, 179
      novel PKs were predicted in the honeybee brain, of which 88 were experimentally
      identified. Proteins involved in wide scenarios of pathways were phosphorylated
      depending on age: glycolysis/gluconeogenesis, AGE/RAGE and phosphorylation in
      nurse bees and metal ion transport, ATP metabolic process and phototransduction
      in forager bees. These observations suggest that phosphorylation is vital to the
      tuning of protein activity to regulate cerebral function according to the
      biological duties as nursing and foraging bees. The data provides valuable
      information on phosphorylation signaling in the honeybee brain and potentially
      useful resource to understand the signaling mechanism in honeybee neurobiology
      and in other social insects as well.

PMID- 28512346
TI  - Cryptic diversity in the Japanese mantis shrimp Oratosquilla oratoria (Crustacea:
      Squillidae): Allopatric diversification, secondary contact and hybridization.
AB  - Mounting evidence of cryptic species in the marine realm emphasizes the necessity
      to thoroughly revise our current perceptions of marine biodiversity and species
      distributions. Here, we used mitochondrial cytochrome oxidase subunit I (mtDNA
      COI) and nuclear ribosomal internal transcribed spacer (nrDNA ITS) to investigate
      cryptic diversity and potential hybridization in the Japanese mantis shrimp
      Oratosquilla oratoria in the Northwestern (NW) Pacific. Both mitochondrial and
      nuclear gene genealogies revealed two cryptic species in this morphotaxon, which
      was further confirmed by extensive population-level analyses. One cryptic species
      is restricted to cold waters with a distribution range corresponding to temperate
      affinities, while the other dwelled warm waters influenced by the Kuroshio
      Current. Their divergence was postulated to be attributable to the vicariant
      event which resulted from the isolation of the Sea of Japan during the middle
      Pliocene (c. 3.85 Mya, 95% HPD 2.23-6.07 Mya). Allopatric speciation was
      maintained by limited genetic exchange due to their habitat preferences.
      Furthermore, the observation of recombinant nrDNA ITS sequence and intra
      individual ITS polymorphism suggested recent hybridization event of the two
      cryptic species occurred in sympatric areas. Our study also illustrated that the
      Changjiang River outflow might act as an oceanic barrier to gene flow and
      promoted allopatric diversification in O. oratoria species complex.

PMID- 28512347
TI  - Insight into the global evolution of Rodentia associated Morbilli-related
      paramyxoviruses.
AB  - One portion of the family Paramyxoviridae is a group of Unclassified Morbilli
      Related Viruses (UMRV) recently recognized in wild small mammals. At a global
      level, the evolutionary history of these viruses is not properly understood and
      the relationships between UMRV and their hosts still remain largely unstudied.
      The present study revealed, for the first time, that Rodentia associated UMRV
      emerged from a common ancestor in southern Africa more than 4000 years ago.
      Sequenced UMRV originating from different regions in the world, clustered into
      four well-supported viral lineages, which suggest that strain diversification
      occurred during host dispersal and associated exchanges, with purifying selection
      pressure as the principal evolutionary force. In addition, multi-introductions on
      different continents and islands of Rodentia associated UMRV and spillover
      between rodent species, most probably Rattus rattus, were detected and indicate
      that these animals are implicated in the vectoring and in the worldwide emergence
      of this virus group. The natural history and the evolution dynamics of these
      zoonotic viruses, originating from and hosted by wild animals, are most likely
      shaped by commensalism related to human activities.

PMID- 28512348
TI  - Adaptive evolution of proteins in hepatitis B virus during divergence of
      genotypes.
AB  - Hepatitis B virus (HBV) is classified into several genotypes, correlated with
      different geographic distributions, clinical outcomes and susceptible human
      populations. It is crucial to investigate the evolutionary significance behind
      the diversification of HBV genotypes, because it improves our understanding of
      their pathological differences and pathogen-host interactions. Here, we performed
      comprehensive analysis of HBV genome sequences collected from public database.
      With a stringent criteria, we generated a dataset of 2992 HBV genomes from eight
      major genotypes. In particular, we applied a specified classification of non
      synonymous and synonymous variants in overlapping regions, to distinguish joint
      and independent gene evolutions. We confirmed the presence of selective
      constraints over non-synonymous variants in consideration of overlapping regions.
      We then performed the McDonald-Kreitman test and revealed adaptive evolutions of
      non-synonymous variants during genotypic differentiation. Remarkably, we
      identified strong positive selection that drove the differentiation of PreS1
      domain, which is an essential regulator involved in viral transmission. Our study
      presents novel evidences for the adaptive evolution of HBV genotypes, which
      suggests that these viruses evolve directionally for maintenance or improvement
      of successful infections.

PMID- 28512349
TI  - The winding path of protein methylation research: milestones and new frontiers.
AB  - In 1959, while analysing the bacterial flagellar proteins, Ambler and Rees
      observed an unknown species of amino acid that they eventually identified as
      methylated lysine. Over half a century later, protein methylation is known to
      have a regulatory role in many essential cellular processes that range from gene
      transcription to signal transduction. However, the road to this now burgeoning
      research field was obstacle-ridden, not least because of the inconspicuous nature
      of the methyl mark itself. Here, we chronicle the milestone achievements and
      discuss the future of protein methylation research.

PMID- 28512352
TI  - Stem cells: Stem cell-based therapies threatened by the accumulation of p53
      mutations.

PMID- 28512353
TI  - Favorable Response to Long-term Nucleos(t)ide Analogue Therapy in HBeAg-positive
      Patients with High Serum Fucosyl-Agalactosyl IgG.
AB  - Aberrant IgG glycosylation is a feature of hepatitis B virus (HBV) infection but
      its effect on a long-term efficacy of antiviral therapy has never been addressed.
      After a screening of 1,085 patients, 132 eligible HBV e antigen (HBeAg)-positive
      and 101 HBeAg-negative patients with anti-HBV nucleos(t)ide analogue monotherapy
      were enrolled with on-treatment follow-ups for at least one year. IgG1 N-glycome
      was profiled using mass spectrometry and evaluated for its relevance in treatment
      responses. The results indicated that a high level of serum fucosyl-agalactosyl
      IgG1 (IgG1-G0F) at baseline was associated with the severity of liver
      inflammation and damage but advanced treatment responses, including HBV DNA loss,
      HBeAg seroconversion, a reduced drug resistance rate, and a liver histological
      improvement at year 1, thereby improving the long-term treatment efficacy and the
      probability of treatment discontinuation in HBeAg-positive patients. Stepwise Cox
      regression analyses revealed that baseline IgG1-G0F >30% was an independent
      factor that links to virological response (HR 3.071, 95% CI 1.835-5.141, P <
      0.001) or HBeAg seroconversion (HR 2.034, 95% CI 1.011-4.093, P = 0.046).
      Furthermore, a high IgG1-G0F level at the treatment endpoint was associated with
      an off-treatment sustained virological response. In conclusion, IgG1-G0F favors
      the medication outcome for HBeAg-positive chronic hepatitis B.

PMID- 28512354
TI  - Neglect Patients Exhibit Egocentric or Allocentric Neglect for the Same Stimulus
      Contingent upon Task Demands.
AB  - Hemispatial Neglect (HN) is a failure to allocate attention to a region of space
      opposite to where damage has occurred in the brain, usually the left side of
      space. It is widely documented that there are two types of neglect: egocentric
      neglect (neglect of information falling on the individual's left side) and
      allocentric neglect (neglect of the left side of each object, regardless of the
      position of that object in relation to the individual). We set out to address
      whether neglect presentation could be modified from egocentric to allocentric
      through manipulating the task demands whilst keeping the physical stimulus
      constant by measuring the eye movement behaviour of a single group of neglect
      patients engaged in two different tasks (copying and tracing). Eye movements and
      behavioural data demonstrated that patients exhibited symptoms consistent with
      egocentric neglect in one task (tracing), and allocentric neglect in another task
      (copying), suggesting that task requirements may influence the nature of the
      neglect symptoms produced by the same individual. Different task demands may be
      able to explain differential neglect symptoms in some individuals.

PMID- 28512356
TI  - Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal
      mucosa of obese rats, are downregulated by three probiotic strains.
AB  - We have previously reported that administration of Lactobacillus paracasei CNCM I
      4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036
      to obese Zucker-Lepr fa/fa rats attenuates liver steatosis and exerts anti
      inflammatory effects. The goal of the present work was to investigate the
      modulation of gene expression in intestinal mucosa samples of obese Zucker-Lepr
      fa/fa rats fed the probiotic strains using a DNA microarray and postgenomic
      techniques. We also measured secretory IgA content in the gut and
      lipopolysaccharide (LPS)-binding protein (LBP) in serum. Expression of three
      genes (Adamdec1, Ednrb and Ptgs1/Cox1) was up-regulated in the intestinal mucosa
      of the obese rats compared with that in the rats when they were still lean.
      Probiotic administration down-regulated expression of Adamdec1 and Ednrb at the
      mRNA and protein levels and that of Ptgs1/Cox1 at the mRNA level, and this effect
      was in part mediated by a decrease in both macrophage and dendritic cell
      populations. Probiotic treatment also increased secretory IgA content and
      diminished the LBP concentration. Based on results reported in this work and else
      where, we propose a possible mechanism of action for these bacterial strains.

PMID- 28512355
TI  - Ancient and recent admixture layers in Sicily and Southern Italy trace multiple
      migration routes along the Mediterranean.
AB  - The Mediterranean shores stretching between Sicily, Southern Italy and the
      Southern Balkans witnessed a long series of migration processes and cultural
      exchanges. Accordingly, present-day population diversity is composed by multiple
      genetic layers, which make the deciphering of different ancestral and historical
      contributes particularly challenging. We address this issue by genotyping 511
      samples from 23 populations of Sicily, Southern Italy, Greece and Albania with
      the Illumina GenoChip Array, also including new samples from Albanian- and Greek
      speaking ethno-linguistic minorities of Southern Italy. Our results reveal a
      shared Mediterranean genetic continuity, extending from Sicily to Cyprus, where
      Southern Italian populations appear genetically closer to Greek-speaking islands
      than to continental Greece. Besides a predominant Neolithic background, we
      identify traces of Post-Neolithic Levantine- and Caucasus-related ancestries,
      compatible with maritime Bronze-Age migrations. We argue that these results may
      have important implications in the cultural history of Europe, such as in the
      diffusion of some Indo-European languages. Instead, recent historical expansions
      from North-Eastern Europe account for the observed differentiation of present-day
      continental Southern Balkan groups. Patterns of IBD-sharing directly reconnect
      Albanian-speaking Arbereshe with a recent Balkan-source origin, while Greek
      speaking communities of Southern Italy cluster with their Italian-speaking
      neighbours suggesting a long-term history of presence in Southern Italy.

PMID- 28512357
TI  - Effect of seed position and soil nutrients on seed mass, germination and seedling
      growth in Peucedanum oreoselinum (Apiaceae).
AB  - There is large variation in seed mass within P. oreoselinum (L.) Moench selected
      for the present study from two contrasting habitats: roadside and oak forest.
      Effect of seed position within a plant and of soil nutrients on seed mass,
      germination and seedlings growth were studied. Within an individual plant, seed
      mass decreased with umbel order and seeds from the central umbellet of the umbel
      were lighter than those from the outer edge, suggesting that variation in seed
      mass within an individual plant was due to the position effect. There was a
      significant relationship between seed mass and total germination. Covariate
      analysis showed the differences between sites in seed macronutrient contents were
      caused by respective differences in seed mass and soil macronutrients. This
      indicates substantial variation in the amount of reserves initially available for
      seedling growth. In conclusion, phenotypically-based variation in seed mass may
      arise from soil conditions, maternal traits or combination of the two. High
      variability in seed mass of P. oreoselinum favours its widespread geographic
      distribution. These results suggest that with respect to germination
      characteristics large seeds from primary order have a competitive advantage over
      small seeds produced on secondary umbels because they have higher overall
      germination.

PMID- 28512351
TI  - Non-homologous DNA end joining and alternative pathways to double-strand break
      repair.
AB  - DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because
      they can result in the loss of large chromosomal regions. In all mammalian cells,
      DSBs that occur throughout the cell cycle are repaired predominantly by the non
      homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity
      to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes
      proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible
      manner. This flexibility permits NHEJ to function on a wide range of DNA-end
      configurations, with the resulting repaired DNA junctions often containing
      mutations. In this Review, we discuss the most recent findings regarding the
      relative involvement of the different NHEJ proteins in the repair of various DNA
      end configurations. We also discuss the shunting of DNA-end repair to the
      auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing
      (SSA) and the relevance of these different pathways to human disease.

PMID- 28512350
TI  - Mechanisms of action and regulation of ATP-dependent chromatin-remodelling
      complexes.
AB  - Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out
      histone sliding, ejection or the incorporation of histone variants, suggesting
      that different mechanisms of action are used by the various chromatin-remodelling
      complex subfamilies. However, all chromatin-remodelling complex subfamilies
      contain an ATPase-translocase 'motor' that translocates DNA from a common
      location within the nucleosome. In this Review, we discuss (and illustrate with
      animations) an alternative, unifying mechanism of chromatin remodelling, which is
      based on the regulation of DNA translocation. We propose the 'hourglass' model of
      remodeller function, in which each remodeller subfamily utilizes diverse
      specialized proteins and protein domains to assist in nucleosome targeting or to
      differentially detect nucleosome epitopes. These modules converge to regulate a
      common DNA translocation mechanism, to inform the conserved ATPase 'motor' on
      whether and how to apply DNA translocation, which together achieve the various
      outcomes of chromatin remodelling: nucleosome assembly, chromatin access and
      nucleosome editing.

PMID- 28512359
TI  - The perceived stability of scenes: serial dependence in ensemble representations.
AB  - We are continuously surrounded by a noisy and ever-changing environment. Instead
      of analyzing all the elements in a scene, our visual system has the ability to
      compress an enormous amount of visual information into ensemble representations,
      such as perceiving a forest instead of every single tree. Still, it is unclear
      why such complex scenes appear to be the same from moment to moment despite
      fluctuations, noise, and discontinuities in retinal images. The general effects
      of change blindness are usually thought to stabilize scene perception, making us
      unaware of minor inconsistencies between scenes. Here, we propose an alternative,
      that stable scene perception is actively achieved by the visual system through
      global serial dependencies: the appearance of scene gist is sequentially
      dependent on the gist perceived in previous moments. To test this hypothesis, we
      used summary statistical information as a proxy for "gist" level, global
      information in a scene. We found evidence for serial dependence in summary
      statistical representations. Furthermore, we show that this kind of serial
      dependence occurs at the ensemble level, where local elements are already merged
      into global representations. Taken together, our results provide a mechanism
      through which serial dependence can promote the apparent consistency of scenes
      over time.

PMID- 28512358
TI  - Delayed epidural transplantation of human induced pluripotent stem cell-derived
      neural progenitors enhances functional recovery after stroke.
AB  - Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a
      promising source of tailor-made cell therapy for neurological diseases. However,
      major obstacles to clinical use still exist. To circumvent complications related
      to intracerebral administration, we implanted human iPSC-NPCs epidurally over the
      peri-infarct cortex 7 days after permanent middle cerebral artery occlusion in
      adult rats. Compared to controls, cell-treated rats showed significant
      improvements in paretic forelimb usage and grip strength from 10 days post
      transplantation (dpt) onwards, as well as reductions in lesion volumes,
      inflammatory infiltration and astrogliosis at 21 dpt. Few iPSC-NPCs migrated into
      rat peri-infarct cortices and exhibited poor survival in tissue. To examine the
      paracrine therapeutic mechanisms of epidural iPSC-NPC grafts, we used
      transmembrane co-cultures of human iPSC-NPCs with rat cortical cells subjected to
      oxygen-glucose deprivation. Compared to other human stem cells, iPSC-NPCs were
      superior at promoting neuronal survival and outgrowth, and mitigating
      astrogliosis. Using comparative whole-genome microarrays and cytokine
      neutralization, we identified a neurorestorative secretome from iPSC-NPCs, and
      neutralizing enriched cytokines abolished neuroprotective effects in co-cultures.
      This proof-of-concept study demonstrates a relatively safe, yet effective
      epidural route for delivering human iPSC-NPCs, which acts predominately through
      discrete paracrine effects to promote functional recovery after stroke.

PMID- 28512360
TI  - Bullying behavior and mental health in healthcare and educational sectors in
      Kaunas, Lithuania.
AB  - BACKGROUND: Investigations on workplace bullying in the countries of Eastern
      Europe are yet not too extensive. The aim of the study has been to identify the
      most frequent bullying behavior and to explore the associations with
      psychological distress and post-traumatic stress symptoms in 3 female-dominated
      occupations in Kaunas, Lithuania. MATERIAL AND METHODS: This crosssectional study
      employed 517 teachers (response rate (RR) = 71.3%), 174 family physicians (RR =
      65.7%) and 311 internal medicine department nurses (RR = 69.1%). The twenty-two
      item Negative Acts Questionnaire was used for measuring the exposure to bullying
      behavior, Goldberg 12-item General Health Questionnaire (GHQ-12) - psychological
      distress, Event Scale-Revised (IES-R) inventory - post-traumatic stress symptoms,
      Karasek & Theorell Demand-Control questionnaire - psychosocial job
      characteristics. The International Business Machines Corporation (IBM) SPSS
      Statistics version 20.0 was used for performing the statistical analysis.
      Logistic regression was used for assessing the associations among 22 negative
      acts as continuous variable and mental health outcomes adjusting to age,
      psychosocial factors at work and everyday life. RESULTS: Exposure to workplace
      bullying behavior on a weekly/daily basis was prevalent among family physicians
      at the rate of 19%, among nurses - 12.9%, among teachers - 4.1%. Even after
      adjustment to age, psychosocial job characteristics and threatening life events,
      the exposure to 22 negative acts as continuous variable was significantly
      associated with psychological distress and post-traumatic stress symptoms for all
      3 occupations. CONCLUSIONS: Health care sector is particularly affected by
      workplace bullying. Exposure to bullying behavior was associated with mental
      health problems for all 3 occupations. Preventive measures are necessary to
      improve psychosocial work environment conditions in healthcare and educational
      institutions in Lithuania. Med Pr 2017;68(3):307-314.

PMID- 28512361
TI  - Quantification of lower extremity physical exposures in various combinations of
      sit/stand time duration associated with sit-stand workstation.
AB  - BACKGROUND: Sit-stand workstations are available for office work purposes but
      there is a dearth of quantitative evidence to state benefits for lower limb
      outcomes while using them. And there are no guidelines on what constitutes
      appropriate sit/stand time duration. The primary aim of this study has been to
      compare muscle activity and perceived discomfort in the lower extremity during
      various combinations of sit/stand time duration associated with a sit-stand
      workstation separately and to evaluate the effects of the sit-stand workstation
      on the lower extremity during the text entry task. MATERIAL AND METHODS: During
      the 5 days, all participants completed a 2-h text entry task each day for various
      sit/stand time duration combinations as follows: 5/25 min, 10/20 min, 15/15 min,
      20/10 min, 25/5 min. Lower extremity muscular exposure of 12 male and 13 female
      participants was collected at 8 sites by surface electromyography and body
      discomfort was calculated by a questionnaire under those 5 conditions. RESULTS:
      Results have demonstrated that lower extremity muscle activity has been
      significantly varied among the 5 sit/stand time duration groups. Perceived level
      of discomfort (PLD) has not differed significantly for 9 out of 10 body parts.
      CONCLUSIONS: The muscle activity of the thigh region was influenced by sit/stand
      time duration significantly. Ergonomic exposures of lower extremity when using a
      sit-stand workstation were increased, particularly during the long time standing
      posture. Results indicate that body mass index (BMI) and gender were not
      significant factors in this study. Combination of sit/stand time duration 25/5
      min appears to show positive effects on relief of muscle exposure of back of
      thigh in the shifts of sitting and standing work position. Med Pr 2017;68(3):315
      327.

PMID- 28512362
TI  - [Copenhagen Psychosocial Questionnaire (COPSOQ) - Psychometric properties of
      selected scales in the Polish version].
AB  - BACKGROUND: The Copenhagen Psychosocial Questionniare (COPSOQ) has many
      advantages as compared to other similar instruments, i.a., it is not related to
      one single theoretical model and it measures a wide spectrum of psychosocial
      working conditions that have shown proven impact on health. The aim of the
      article is to summarize information on psychometric properties of 11 scales in
      the Polish version: Quantitative Demands, Emotional Demands, Influence at Work,
      Social Support, Possibilities for Development, Meaning of Work, Role Clarity,
      Quality of Leadership, Job Insecurity, Job Satisfaction, and General Health.
      MATERIAL AND METHODS: Analyses were based on the results of 4 research projects,
      in which the Polish version of the COPCOQ scales has been used: on a
      representative sample of Polish nurses (N = 4354), job insecurity in 2 groups of
      civil servants (N = 295, N = 724), mobbing among teachers (N = 1037) and
      psychological consequences of restructuring (N = 1396). The following
      psychometric characteristics were analysed: internal reliability, theoretical
      validity, and factorial validity. RESULTS: Internal reliability of the following
      8 scales was found satisfactory: Quantitative Demands, Influence at Work, Social
      Support, Possibilities for Development, Meaning of Work, Quality of Leadership,
      Job Satisfaction, and General Health (Cronbach's alpha = 0.7-0.91, depending on
      the scale). The results of exploratory factor analyses indicated factorial
      separateness of the above mentioned scales. Theoretical validity of 11 scales was
      confirmed; they were associated with variables that can be regarded as their
      validity criteria. CONCLUSIONS: The 8 COPSOQ scales, in the Polish version, can
      be recommended for using in the research involving psychosocial job
      characteristics. Mean scores on these scales and standard deviations given in the
      article can serve as reference points during an evaluation of received results.
      Med Pr 2017;68(3):329-348.

PMID- 28512364
TI  - [Radiographic implications of procedures involving cardiac implantable electronic
      devices (CIEDs) - Selected aspects].
AB  - BACKGROUND: Some cardiac implantable electronic device (CIED) implantation
      procedures require the use of X-rays, which is reflected by such parameters as
      total fluoroscopy time (TFT) and dose-area product (DAP - defined as the absorbed
      dose multiplied by the area irradiated). MATERIAL AND METHODS: This retrospective
      study evaluated 522 CIED implantation (424 de novo and 98 device upgrade and new
      lead placement) procedures in 176 women and 346 men (mean age 75+/-11 years) over
      the period 2012-2015. The recorded procedure-related parameters TFT and DAP were
      evaluated in the subgroups specified below. The group of 424 de novo procedures
      included 203 pacemaker (PM) and 171 implantable cardioverter-defibrillator (ICD)
      implantation procedures, separately stratified by single-chamber and dual-chamber
      systems. Another subgroup of de novo procedures involved 50 cardiac
      resynchronization therapy (CRT) devices. The evaluated parameters in the group of
      98 upgrade procedures were compared between 2 subgroups: CRT only and combined PM
      and ICD implantation procedures. RESULTS: We observed differences in TFT and DAP
      values between procedure types, with PM-related procedures showing the lowest,
      ICD - intermediate (with values for single-chamber considerably lower than those
      for dual-chamber systems) and CRT implantation procedures - highest X-ray
      exposure. Upgrades to CRT were associated with 4 times higher TFT and DAP values
      in comparison to those during other upgrade procedures. Cardiac resynchronization
      therapy de novo implantation procedures and upgrades to CRT showed similar mean
      values of these evaluated parameters. CONCLUSIONS: Total fluoroscopy time and DAP
      values correlated progressively with CIED implantation procedure complexity, with
      CRT-related procedures showing the highest values of both parameters. Med Pr
      2017;68(3):363-374.

PMID- 28512363
TI  - [Attenuation of earmuffs used simultaneously with respiratory protective
      devices].
AB  - BACKGROUND: In the work environment, apart from the noise, employees may be
      exposed to other harmful factors. Therefore, they wear hearing protectors and
      other personal protective equipment. The aim of the study was to determine
      whether simultaneous use of earmuffs and respiratory protective devices affects
      the attenuation of earmuffs. MATERIAL AND METHODS: The study was conducted in
      laboratory conditions using the subjective REAT (Real Ear Attenuation at
      Threshold) and objective MIRE (Microphone in Real Ear) methods. The REAT method
      was used to measure sound attenuation of earmuffs, while MIRE was used to
      determine changes in attenuation of earmuffs due to the use of other personal
      protective equipment. RESULTS: The study showed reduction in attenuation of
      earmuffs due to the use of a full face mask up to 20 dB. Using a full face mask
      causes that attenuation of earmuffs in the low frequency range is close to zero.
      Reduction in attenuation due to the use of half masks for complete with particle
      filters (half masks) is 3-15 dB. Simultaneous use of earmuffs and filtering half
      masks makes small changes in attenuation not exceeding 3 dB. CONCLUSIONS: The
      study showed that full face masks give the greatest reduction in attenuation of
      earmuffs. On the other hand, the least reduction is observed in the case of
      filtering half masks. There is a significant difference between the reduction in
      attenuation of earmuffs worn with half masks for complete with particle filters
      because they may be equipped with different kind of the head strap. Med Pr
      2017;68(3):349-361.

PMID- 28512365
TI  - [Temperament risk factor for mental health disturbances in the judiciary staff].
AB  - BACKGROUND: The aim of this paper was to examine how temperament might moderate
      the health impact of psychosocial hazards at work and thus to attempt to identify
      the temperament risk factor in the judiciary staff. MATERIAL AND METHODS: The
      data were collected from 355 court employees, including judges, judicial
      assistants, court clerks and service workers from criminal, civil, commercial as
      well as from labor and social insurance divisions. The psychosocial work
      environment was measured with the Psychosocial Working Conditions Questionnaire
      by Cieslak and Widerszal-Bazyl, temperament with Cloninger's Temperament and
      Character Inventory adopted by Hornowska and employee health status was screened
      with Goldberg's General Health Questionnaire- 28 (GHQ-28) adopted by Makowska and
      Merecz. The health impact of job strain with moderating effects of temperament
      traits was estimated with logistic regression (forward stepwise selection based
      on the likelihood ratio for the model). RESULTS: The analyses confirmed the
      moderating role of temperament in the health consequences of work-related stress.
      High score in novelty seeking was identified as independent temperament risk
      factor for mental health disturbances in judiciary staff facing at least medium
      job demands. The job control was a protective factor while relative risk of
      negative health outcomes was also elevated due to female gender. CONCLUSIONS:
      Temperament may control sensitivity to the environmental exposure to psychosocial
      hazards at work and its health consequences. Further research is needed to
      explore and understand better the moderating role of temperament in the relation
      between job stress (strain) and health in different vocational groups and
      workplaces. Med Pr 2017;68(3):375-390.

PMID- 28512366
TI  - [Effect of alpha-lipoic acid on free radical processes in serum of rats on high
      fat diet].
AB  - BACKGROUND: Oils are often fried which reduces their beneficial biological and
      nutritional properties, contributing to disturbances in homeostasis. Some
      antioxidant substances can improve stability of oils. The aim of the study was to
      examine the effect of alpha-lipoic acid (ALA) on the concentration of sulfhydryl
      groups, lipid peroxides, malondialdehyde, creatinine and urea in serum of rats
      fed high fat diet for 3 months. MATERIAL AND METHODS: Thirty six Wistar rats were
      equally divided into 6 groups: the control group on standard breeding diet (SB),
      oxidized oil (OU) group on SB with 10% oxidized oil, ALA10 group on SB with ALA
      10 mg/kg of body weight (b.w.), OU+ALA10 group on SB with oxidized oil and ALA
      (10 mg/kg b.w.), ALA50 group on SB with ALA in a dose of 50 mg/kg b.w., OU+ALA50
      group on SB with oxidized oil and ALA (50 mg/kg b.w.). Oil was oxidized in 180
      degrees C for 6 h. RESULTS: We observed decrease in concentration of protein
      sulfhydryl (PSH) groups in all study groups except for ALA10 vs. control group
      (C) and increase in OU+ALA10 and OU+ALA50 vs. OU; increase in the lipid
      hydroperoxide (LHP) concentration in OU, OU+ALA10 and OU+ALA50 vs. C and decrease
      in all study groups vs. OU; increase of malondialdehyde (MDA) in OU vs. all other
      groups. And also increase in creatinine and urea concentration in OU group.
      CONCLUSIONS: High fat diet rich in oxidized oil intensifies the lipid
      peroxidation process and oxidation of sulfhydryl groups. It can also impair
      kidney function. Administration of lipoic acid in a dose of 10 mg/kg b.w.
      inhibits the lipid peroxidation and protects sulfhydryl groups. Med Pr
      2017;68(3):391-399.

PMID- 28512367
TI  - [Theoretical models of drivers behavior on the road].
AB  - Understanding of mechanisms and factors responsible for the driver behavior on
      the road is the subject of ongoing interest to transportation psychologists,
      occupational doctors and engineers. Models of driver behavior are a key point for
      the understanding the mechanisms and factors which may cause limitations to the
      optimal functioning on the road. They also systematize knowledge about the
      factors responsible for the behavior of the driver and thus constitute a starting
      point for formulating empirical or diagnostic hypotheses. The aim of this study
      is to present models of driver behavior from the descriptive and functional
      perspectives. Med Pr 2017;68(3):401-411.

PMID- 28512368
TI  - [Analysis of the phenomenon of over-the-counter drug abuse and not controlled
      herbs trade by polish adolescents: Part I].
AB  - The phenomenon of stupefying by the use of available over-the-counter drugs (OTC)
      among adolescents is an essential problem in both Poland and throughout the
      world. Popular analgesics, cold medicine and antihistamines contain psychedelic
      substances, such as dextromethorphan (DXM), pseudoephedrine/ephedrine, codeine
      (methylmorphine), dimenhydrinate, paracetamol (acetaminophren) and others. Cases
      of fatal addiction to dextromethorphan, one of the active substances contained in
      medicines, e.g., the common cold, have been reported. The test results cited by
      the authors clearly indicate that the use of OTC drugs, whose turnover is not
      controlled is a domain of females. The extent of use of drugs not prescribed by a
      doctor has remained for many years at a constant level. The most common
      poisonings with OTC drugs are caused by those that affect the respiratory system
      or exert analgesic or antipyretic effects. They are also used in attempted
      suicides, especially among females. Analyzing poisonings caused by OTC
      medications their seasonality has been observed. Their number increases during
      spring-autumn. A territorial differentiation in areas of OTC drug trade in terms
      of their quantities, with the predominance of southern regions is also noted.
      Intoxication with psychoactive substances causes the deterioration of relations
      between young people. In the reviewed studies there is no detailed information on
      the composition of non-prescription medicines. Moreover, young people have easy
      access to mushroom fungi, growing in nearby forests and meadows that may have
      hallucinogenic effects and are available in pharmacies and on the Internet. Med
      Pr 2017;68(3):413-422.

PMID- 28512369
TI  - [Nanopesticides - Light or dark side of the force?]
AB  - Nanotechnology has been used in many branches of industry, including agriculture,
      where nanomaterials are used as carriers of chemical plant protection compounds,
      as well as active ingredients. Meanwhile, the effects of nanopesticides exposure
      on the human body are unknown. Due to their occupation, farmers should be
      particularly monitored. This paper summarizes the use of nanoparticles in
      agriculture, the route of potential exposure for agricultural workers and the
      current state of knowledge of nanopesticides toxicity to mammalian cells. The
      authors also discuss techniques for detecting nanoparticles in the workplace, as
      well as biomarkers and effects of exposure. The results of this review indicate
      that the use of nanotechnology in agriculture can bring measurable benefits by
      reducing the amount of chemicals used for plant protection. However, there is no
      research available to determine whether or not the use of pesticide
      nanoformulations increases the harmful effects of pesticides. Moreover, the
      results of research on cell lines and in animal models suggest that nanoparticles
      used as active substance are toxic to mammalian cells. Interestingly, there is
      also a complete lack of epidemiological studies on this subject. In the nearest
      future the effects of exposure to nanopesticides may require a particular
      attention paid by scientists and medical doctors who, treat agricultural workers
      and their families. Med Pr 2017;68(3):423-432.

PMID- 28512370
TI  - Occupational contact allergy to omeprazole and ranitidine.
AB  - Omeprazole is a proton pump inhibition and ranitidine is an H2 histamine receptor
      antagonist widely used in the treatment of gastroesophageal reflex disease,
      peptic ulcer disease, Zollinger-Ellison syndrome and as a protector of the
      gastric mucosae. We report a case of occupational contact allergy to omeprazole
      and ranitidine. A 48-year-old man, with no pre-existing history of atopy or
      lifestyle factors. He neither had any medical history of consumption of drugs
      such as ranitidine and omeprazole. He worked for 19 months in the pharmaceutical
      company that manufactured ranitidine base. He presented rash in the face and
      eczema on the dorsum of the hands with itching. The study by prick tests with
      ranitidine gave negative response. Patch testing with ranitidine base and
      ranitidine hydrochloride gave positive response. A month later, when the patient
      was asymptomatic he returned to the pharmaceutical company, being switched from
      this previous job to the reactor manufacturing omeprazole. A few days after that,
      he presented erythematous eruptions involving face and neck with itching. Prick
      tests, path tests and in vitro laboratories studies with omeprazole gave
      positives. In this case the patient presented hypersensitivity type I at
      omeprazole and hypersensitivity type IV at omeprazole and ranitidine. Our
      aportation indicates the importance of careful analysis of the occupational
      exposure histories of patients with the suspected type I or type IV
      hypersensitivity to allergens, to determine whether work exposure is the cause.
      Med Pr 2017;68(3):433-435.

PMID- 28512371
TI  - First Report of the Spiral Nematode Helicotylenchus microlobus Infecting Soybean
      in North Dakota.
AB  - Spiral nematodes (Helicotylenchus spp.) are common plant-parasitic nematodes in
      fields of many crops. In June 2015, two soil samples were collected from a
      soybean field in Richland County, ND. Nematodes were extracted from soil using
      the sugar centrifugal flotation method (Jenkins, 1964). Plant-parasitic nematodes
      were identified to genus based on morphological features and counted. Both
      samples contained spiral nematodes from 1,500 to 3,300 per kilogram of soil. In
      June and August 2016, 10 soil samples were collected from the same field.
      Nematodes were extracted, and nine of the samples had spiral nematodes ranging
      from 125 to 3,065 per kilogram of soil. One soil sample with 1,500 spiral
      nematodes per kilogram was used to inoculate two soybean cultivars Sheyenne and
      Barnes each in four replicates. After 15 wk of growth at 22 degrees C in a
      greenhouse room, the population of spiral nematodes was found to have increased
      greatly. The final density was 9,300 +/- 1,701 spiral nematodes per kilogram of
      soil for Sheyenne and 9,451 +/- 2,751 for Barnes. The reproductive factor in
      Sheyenne and Barnes was 6.2 and 6.3, respectively, indicating that this spiral
      nematode infects and reproduces well on these two soybean cultivars. Infected
      soybean roots had small brown lesions on the surface. Individual spiral nematodes
      were handpicked and examined morphologically and molecularly for species
      identification. Morphological measurements of adult females (n = 15) included
      body length (mean = 708.5 MUm, range = 600.0-812.0 MUm), stylet (27.6, 26.0
      29.0), body width (28.3, 25.0-33.0), lip region end to posterior end of
      pharyngeal glands (142.5, 130.0-152.0), anal body width (15.8, 14.0-17.5), tail
      length (20.3, 15.0-25.0), tail annules (11.6, 10.0-14.0), a (25.0, 21.4-27.1), b
      (5.0, 4.4-5.7), c (35.4, 30.2-41.7), c' (1.3, 1.0-1.6), and V (61.8%, 60.0-63.7).
      The spiral nematode was identified as Helicotylenchus microlobus according to
      morphological and morphometric characteristics (Subbotin et al., 2015). DNA was
      extracted from single nematodes (n = 8) using the Proteinase K method (Kumari and
      Subbotin, 2012). The internal transcribed spacer (ITS) region of rDNA was
      amplified with the primers rDNA2/rDNA1.58S (Cherry et al., 1997). The PCR
      products were then purified and sequenced. The consensus ITS rDNA sequence
      (accession no. KY271078, 822 bp) that was deposited into the GenBank shared 99%
      identity with two isolates of H. microlobus from California (KM506860.1 and
      KM506859.1) and one isolate of H. microlobus from Spain (KM506862.1) (Subbotin et
      al., 2015). It had only 91% sequence identity with seven isolates of H.
      pseudorobustus (KM506875.1, KM506880.1, KM506876.1, KM506874.1, KM506872.1,
      KM506879.1, and KM506878.1) from California, Switzerland, and New Zealand, a
      spiral nematode species very closely related to H. microlobus in morphology. The
      molecular tests confirmed the identity of this spiral nematode as H. microlobus.
      The H. microlobus nematode was reported as one of the most commonly observed
      spiral nematodes in soil samples in the state of Minnesota, and all 13 soybean
      cultivars tested except Hawkeye were rated as hosts (Taylor, 1960). To our
      knowledge, this is the first report of H. microlobus in North Dakota.

PMID- 28512372
TI  - Characterization of Lilium longiflorum cv. 'Nellie White' Infection with Root
      lesion Nematode Pratylenchus penetrans by Bright-field and Transmission Electron
      Microscopy.
AB  - Lilium longiflorum cv. Nellie White, commonly known as Easter lily, is an
      important floral crop with an annual wholesale value of over $26 million in the
      United States. The root-lesion nematode, Pratylenchus penetrans, is a major pest
      of lily due to the significant root damage it causes. In this study, we
      investigated the cytological aspects of this plant-nematode interaction using
      bright-field and transmission electron microscopy. We took advantage of an in
      vitro culture method to multiply lilies and follow the nematode infection over
      time. Phenotypic reactions of roots inoculated with P. penetrans were evaluated
      from 0 to 60 d after nematode infection. Symptom development progressed from
      initial randomly distributed discrete necrotic areas to advanced necrosis along
      entire roots of each inoculated plant. A major feature characterizing this
      susceptible host response to nematode infection was the formation of necrosis,
      browning, and tissue death involving both root epidermis and cortical cells.
      Degradation of consecutive cell walls resulted in loss of cell pressure, lack of
      cytoplasmic integrity, followed by cell death along the intracellular path of the
      nematode's migration. Pratylenchus penetrans was never seen in the vascular
      cylinder as the layer of collapsed endodermal cells presumably blocked the
      progression of nematodes into this area of the roots. This study presents the
      first detailed cytological characterization of P. penetrans infection of Easter
      lily plants.

PMID- 28512373
TI  - Assessment of Globodera pallida RNA Extracted from Solanum Roots.
AB  - The introduction of high-throughput sequencing technologies has made
      transcriptome analyses of plant-pathogen interactions almost routine.
      Nevertheless, it is still challenging to obtain RNA from populations made up of
      two species. An RNA extraction method that worked well on free-living
      Caenorhabditis elegans failed when applied to isolated Globodera pallida J2
      larva. Furthermore, alternative protocols that extracted RNA from free-living J2
      larva produced less satisfactory results once the animals entered their hosts'
      roots. We have compared several extraction procedures to ascertain whether a
      single protocol was capable of recovering high-quality, high-molecular-weight RNA
      from newly hatched J2 larva as well as from larva embedded in roots of both
      potatoes (Solanum tuberosum L. cv. Desiree) and a very distantly related species,
      Solanum sisymbriifolium. Although it was possible to recover large amounts of RNA
      from J2 larvae using Proteinase K treatments, this protocol failed to yield high
      quality nematode RNA from infected roots. By comparison, mechanical disruption
      procedures yielded lower amounts of RNA from infected roots, but what was
      recovered was of higher quality. We conclude that different extraction protocols
      need to be developed to sample mixed populations of organisms.

PMID- 28512374
TI  - Description of Enchodorus yeatsi n. sp. (Dorylaimida, Nordiidae) from Southern
      Iran and Its Molecular Phylogenetic Study.
AB  - Enchodorus yeatsi n. sp., a new species of the rare genus Enchodorus is described
      and illustrated based on its morphological and molecular characters. It was
      recovered from southern Iran. Females of the new species are characterized by
      having 1,511.3- to 1,792.5-um long slender body, angular lip region having
      prominent papillae, 12- to 13-um long odontostyle, double guiding ring, simple
      rod-like odontophore, didelphic-amphidelphic reproductive system, and 102- to 160
      um long elongate-conoid tail with rounded tip. Males of the new species are
      abundant and functional, characterized by 1,484- to 1,576-um long body, 40- to 43
      um long spicules, 5 to 6 ventromedian supplements, and ventrally bent elongate
      conical tail. Compared to the type species, Enchodorus dolichurus, the new
      species has differences in its tail morphology and V value. These morphological
      differences and the separation of two species was further supported with basic
      differences in sequences of 28S rDNA D2/D3 and internal transcribed spacer 1
      (ITS1) fragments. Compared to Enchodorus neodolichurus, it has basic differences
      in tail characters and spicule lengths. Molecular phylogenetic studies using
      partial sequences of 28S rDNA D2/D3 fragment of the new species and available
      sequences of Nordiidae members and several other dorylaim species/genera,
      revealed E. yeatsi n. sp. and E. dolichurus forming a clade with 0.81 Bayesian
      posterior probability (BPP). This clade forms a sister clade to the clade of
      Heterodorus sp. and Rhyssocolpus vinciguerrae, again with 0.81 BPP. In ITS1 tree,
      reconstructed using few available sequences, the new species and E. dolichurus
      formed a clade with 0.98 BPP.

PMID- 28512375
TI  - A Simple Express Technique to Process Nematodes for Collection Slide Mounts.
AB  - The new simple technique of hot fixation and a method for processing a mass
      quantity of nematodes to prepare nematode collection slides for taxonomic and
      ecological purposes, combined with an abrupt reduction of the set of procedures
      caused by the "cocktail" principle (a stratification of layers with a gradient of
      glycerol concentrations), are described.

PMID- 28512376
TI  - Oscheius microvilli n. sp. (Nematoda: Rhabditidae): A Facultatively Pathogenic
      Nematode from Chongming Island, China.
AB  - A new species, Oscheius microvilli n. sp., was found on Chongming Island
      (Shanghai, China). The new species is morphologically similar to the type strain
      of Oscheius myriophilus, but can be distinguished from it and other species of
      Oscheius on the basis of unique morphological characteristics of the bursa as
      well as male papillae. In this new species, the male bursal papillar formula is
      2, 1, 3, 3 with everted tips in the first, fifth, and seventh pairs. The bursal
      rim is jagged, joins together anterior to the spicules, and is partially extended
      and decorated with microvilli. The spicules are incompletely separated, and the
      tail does not extend beyond the bursa. Phylogenetic trees of 18S rDNA and
      internal transcribed spacer indicate that the new species belongs to the
      insectivora group of the genus Oscheius; it is most closely related to O.
      myriophilus, and the two species can be distinguished on the basis of their
      different body length, morphological features of the bursa, and molecular data.
      The new species is facultatively associated with a bacterial strain of Serratia.
      The LC50 of this novel nematode against Galleria mellonella was 69.1 dauer
      juveniles per milliliter after 48 hr of infection.

PMID- 28512377
TI  - Species Delimitation and Description of Mesocriconema nebraskense n. sp.
      (Nematoda: Criconematidae), a Morphologically Cryptic, Parthenogenetic Species
      from North American Grasslands.
AB  - Nematode surveys of North American grasslands conducted from 2010 to 2015
      frequently recovered a species of criconematid nematode morphologically
      resembling Mesocriconema curvatum. These specimens were recovered from remnant
      native prairies in the central tallgrass ecoregion of North America, and not from
      surrounding agroecosystems. Historical records indicate that M. curvatum is a
      cosmopolitan species feeding on a wide range of agronomic and native plants. DNA
      barcoding indicates North American grasslands contain at least 10
      phylogenetically distinct lineages of Mesocriconema that resemble, but are not,
      M. curvatum. Analysis of the two most common lineages reveals two distinctly
      different population structures. The variation in population structure suggests
      unique evolutionary histories associated with their diversification. These two
      major lineages share a sympatric distribution and their slight morphological
      differences contrast with a high level of genetic separation. Based on their
      genetic divergence, fixed diagnostic nucleotides, population structure, species
      delimitation metrics, and a sympatric distribution, we believe that one of these
      distinct lineages warrants formal nomenclatural recognition. Herein, we provide
      formal recognition for Mesocriconema nebraskense n. sp. and discuss its
      relationship to other Mesocriconema lineages discovered in native North American
      grasslands.

PMID- 28512378
TI  - Description of Aphelenchoides macrospica n. sp. (Nematoda: Aphelenchoididae) from
      Northwestern Iran.
AB  - Aphelenchoides macrospica n. sp. is described and illustrated from the West
      Azerbayjan province, northwestern Iran. The new species is characterized by its
      body length of 807 to 963 MUm (males) and 792 to 1,094 MUm (females), offset
      cephalic region, lateral fields with four incisures, long stylet with 15 to 16
      MUm length, and excretory pore situated opposite or behind the nerve ring.
      Pharyngeal glands overlapping intestine dorsally and extending for 90 to 121 MUm,
      tail terminus mucronate in both sexes. Vagina directed anteriad, and spicules are
      relatively large (27-32 MUm) with well-developed broadly rounded apex and
      condylus. The new species comes close to seven known species of the genus namely
      A. arcticus, A. blastophthorus, A. haguei, A. huntensis, A. lucknowensis, A.
      parasaprophilus, and A. xui, but it differs from them by the body size, stylet
      length, size of spicules, and length of postvulval uterine sac. The results of
      phylogenetic analyses based on sequences of D2-D3 expansion region of 28S and 18S
      rDNA, confirmed its status as a new species.

PMID- 28512379
TI  - Evaluation of Pochonia chlamydosporia and Purpureocillium lilacinum for
      Suppression of Meloidogyne enterolobii on Tomato and Banana.
AB  - Meloidogyne enterolobii is one of the most important root-knot nematode in
      tropical regions, due to its ability to overcome resistance mechanisms of a
      number of host plants. The lack of new and safe active ingredients against this
      nematode has restricted control alternatives for growers. Egg-parasitic fungi
      have been considered as potential candidates for the development of
      bionematicides. In tissue culture plates, Pochonia chlamydosporia (var.
      catenulata and chlamydosporia) and Purpureocillium lilacinum strains were
      screened for their ability to infect eggs of the root-knot nematode M.
      enterolobii on water-agar surfaces. Reduction in the hatching of J2 varied from
      13% to 84%, depending on strain. The more efficacious strains reduced
      hatchability of J2 by 57% to 84% when compared to untreated eggs, but average
      reductions were only 37% to 55% when the same strains were applied to egg masses.
      Combinations of fungal isolates (one of each species) did not increase the
      control efficacy in vitro. In experiments in which 10,000 nematode eggs were
      inoculated per plant, reductions in the number of eggs after 12 months were seen
      in three of four treatments in banana plants, reaching 34% for P. chlamydosporia
      var. catenulata. No significant reductions were seen in tomato plants after 3
      mon. In another experiment with tomato plants using either P. chlamydosporia var.
      catenulata or P. lilacinum, the number of eggs was reduced by 34% and 44%,
      respectively, when initial infestation level was low (500 nematode eggs per
      plant), but tested strains were not effective under a moderate infestation level
      (5,000 eggs per plant). Under all infestation levels tested in this work, gall
      and egg mass indexes (MI) did not differ from the untreated controls, bringing
      concerns related to the practical adoption of this control strategy by farmers.
      In our opinion, if the fungi P. chlamydosporia and P. lilacinum are to be used as
      biocontrol tools toward M. entorolobii, they should focus on agricultural
      settings with low soil infestation levels and within an IPM approach.

PMID- 28512380
TI  - Esteya vermicola Controls the Pinewood Nematode, Bursaphelenchus xylophilus, in
      Pine Seedlings.
AB  - Esteya vermicola (Ophiostomataceae) is an endoparasitic fungus that has great
      potential as a biological control agent against the pinewood nematode
      Bursaphelenchus xylophilus which causes pine wilt disease. We tested E. vermicola
      for control of pine wilt disease by spraying E. vermicola conidia on artificial
      wounds on pine seedlings, and the optimum E. vermicola treatment density and
      application time were also investigated in the greenhouse. The wounds were
      similar to those made by sawyer beetles (Coleoptera: Cerambycidae). Esteya
      vermicola treatments significantly increased the survival rate of pine seedlings
      that were infected by pinewood nematodes. Wounded plants sprayed with 107 CFU/ml
      E. vermicola had a 73.0% greater survival rate than nonwounded pine seedlings
      treated similarly. The treatment of pine seedlings with 107 CFU/ml E. vermicola
      14 d before nematode infection increased their survival rate by 90.0%. The number
      of pinewood nematodes isolated from dead pine seedlings sprayed with E. vermicola
      was 76% less than the number of pinewood nematodes in the controls. Moreover,
      infected nematodes and the hyphae of E. vermicola were detected in the dead or
      wilting pine seedlings. Therefore, spraying E. vermicola on the wounds of pine
      seedlings made by sawyer beetles provides good control of the pine wilt disease
      that is caused by pinewood nematodes.

PMID- 28512381
TI  - First Report and Comparative Study of Steinernema surkhetense (Rhabditida:
      Steinernematidae) and its Symbiont Bacteria from Subcontinental India.
AB  - Two populations (CS19 and CS20) of entomopathogenic nematodes were isolated from
      the soils of vegetable fields from Bijnor district, India. Based on
      morphological, morphometrical, and molecular studies, the nematodes were
      identified as Steinernema surkhetense. This work represents the first report of
      this species in India. The infective juveniles (IJs) showed morphometrical and
      morphological differences, with the original description based on longer IJs
      size. The IJs of the Indian isolates possess six ridges in their lateral field
      instead of eight reported in the original description. The analysis of ITS-rDNA
      sequences revealed nucleotide differences at 345, 608, and 920 positions in
      aligned data. No difference was observed in D2-D3 domain. The S. surkhetense COI
      gene was studied for the first time as well as the molecular characterization of
      their Xenorhabdus symbiont using the sequences of recA and gyrB genes revealing
      Xenorhabdus stockiae as its symbiont. These data, together with the finding of X.
      stockiae, suggest that this bacterium is widespread among South Asian nematodes
      from the "carpocapsae" group. Virulence of both isolates was tested on Spodoptera
      litura. The strain CS19 was capable to kill the larvae with 31.78 IJs at 72 hr,
      whereas CS20 needed 67.7 IJs.

PMID- 28512382
TI  - Occurrence of Belonolaimus in Sinaloa, Northwestern Mexico: A New Report on
      Distribution and Host Range.
AB  - The present study reports the occurrence of the genus Belonolaimus in the state
      of Sinaloa, Mexico, associated with native plants (i.e., Ziziphus amole and
      Stenocereus alamosensis) in a natural coastal ecosystem. Both morphological and
      molecular approaches were employed to characterize the Sinaloa population.
      Notwithstanding of some morphological and morphometric variation between
      Belonolaimus from Sinaloa and other valid species, the characterization indicates
      that this population might belong to the Belonolaimus longicaudatus species
      complex. Molecular analyses based on the 28S gene and ITS1-5.8S-ITS2 regions of
      the ribosomal RNA (rRNA) identified four major clades within Belonolaimus;
      however, none of the species including B. longicaudatus, B. gracilis, and B.
      euthychilus were supported as monophyletic; yet monophyly is argued to be a basic
      requirement of species status. Sequence divergence among different Belonolaimus
      populations and species varied according to the rRNA dataset (i.e., ITS1-5.8S
      ITS2 > 28S > 18S) used, thus showing the importance of using genes with different
      rates of evolution to estimate species relationships. The fact that Belonolaimus
      has not been found in other cultivated (including on suitable hosts) areas in
      Sinaloa and that this population is relatively distant from the common B.
      longicaudatus groups (i.e., clades A and B) suggests that its appearance was not
      due to a recent introduction associated with the local agriculture.

PMID- 28512384
TI  - Erratum.
AB  - [This corrects the article on p. 280 in vol. 48, PMID: 28154434.].

PMID- 28512383
TI  - Effects of Cover Crops on Pratylenchus penetrans and the Nematode Community in
      Carrot Production.
AB  - Cover cropping is a common practice in U.S. Midwest carrot production for soil
      conservation, and may affect soil ecology and plant-parasitic nematodes-to which
      carrots are very susceptible. This study assessed the impact of cover crops-oats
      (Avena sativa), radish (Raphanus sativus) cv. Defender, rape (Brassica napus) cv.
      Dwarf Essex, and a mixture of oats and radish-on plant-parasitic nematodes and
      soil ecology based on the nematode community in Michigan carrot production
      systems. Research was conducted at two field sites where cover crops were grown
      in Fall 2014 preceding Summer 2015 carrot production. At Site 1, root-lesion
      (Pratylenchus penetrans) and stunt (Tylenchorhynchus sp.) nematodes were present
      at low population densities (less than 25 nematodes/100 cm3 soil), but were not
      significantly affected (P > 0.05) by cover crops. At Site 2, P. penetrans
      population densities were increased (P <= 0.05) by 'Defender' radish compared to
      other cover crops or fallow control during cover crop growth and midseason carrot
      production. At both sites, there were few short-term impacts of cover cropping on
      soil ecology based on the nematode community. At Site 1, only at carrot harvest,
      radish-oats mixture and 'Dwarf Essex' rape alone enriched the soil food web based
      on the enrichment index (P <= 0.05) while rape and radish increased structure
      index values. At Site 2, bacterivore abundance was increased by oats or radish
      cover crops compared to control, but only during carrot production. In general,
      cover crops did not affect the nematode community until nearly a year after cover
      crop growth suggesting that changes in the soil community following cover
      cropping may be gradual.

PMID- 28512385
TI  - Association of PECAM-1 Gene Polymorphisms with Kawasaki Disease in Chinese
      Children.
AB  - Kawasaki disease (KD) is an acute systemic vasculitis complicated by development
      of coronary artery lesions. PECAM-1 is a kind of cell adhesion molecule, which
      plays an important role in coronary artery disease. The relationship between
      PECAM-1 gene polymorphisms and their susceptibility to Kawasaki diseases (KD) is
      still unclear. In our study, we examined the PECAM-1 gene polymorphisms in 44 KD
      patients and 59 healthy children and revealed the correlation of PECAM-1 gene
      polymorphisms in KD children with and without coronary artery lesions (CAL).

PMID- 28512386
TI  - Oxidative Stress Biomarkers: Establishment of Reference Values for Isoprostanes,
      AOPP, and NPBI in Cord Blood.
AB  - Oxidative stress (OS) is a common pathogenic factor involved in the onset of
      several diseases in humans, from immunologic disorders to malignancy, being a
      serious public health problem. In perinatal period, OS has been associated with
      adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are
      mediated by increased production of free radicals (FRs) following various
      mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation,
      mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism. FRs
      have short half-life, and their measurement in vivo is faced with many
      challenges. However, oxyradical derivatives are stable and thus may be measured
      and monitored repeatedly. The quantification of OS is based on the measurement of
      specific biomarkers in biologic fluids and tissues, which reflect induced
      oxidative damage to lipids, proteins, and DNA. Prostanoids, non-protein-bound
      iron (NPBI), and advanced oxidation protein products (AOPP) are actually
      considered truly specific and reliable for neonatal injury. Defining reference
      values for these biomarkers is necessary to investigate their role in neonatal
      diseases or also to evaluate the success of treatments. In this work, we wanted
      to define laboratory reference values for biomarkers of OS in a healthy
      population of term newborns.

PMID- 28512389
TI  - Evaluation of Quality of Life at Progression in Patients with Soft Tissue
      Sarcoma.
AB  - Introduction. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal
      tissue, with international incidence estimates between 1.8 and 5 per 100,000 per
      year. Understanding quality of life (QoL) and the detrimental impact of disease
      progression is critical for long-term care and survival. Objectives. The primary
      objective was to explore the relationship between disease progression and health
      related quality of life (HRQoL) using data from Eisai's study (E7389-G000-309).
      Methods. This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study
      comparing the efficacy and safety of eribulin versus dacarbazine in patients with
      advanced STS. The QoL analysis was conducted for the baseline and progression
      populations using the European Organization for Research and Treatment of Cancer
      30-item core QoL questionnaire (EORTC QLQ-C30). Results. There were no
      statistical differences between the two treatment arms at baseline for any domain
      (p > 0.05; n = 452). Of the 399 patients who experienced disease progression
      (unadjusted and adjusting for histology), dacarbazine patients had significantly
      lower Global Health Status, Physical Functioning scores, and significantly worse
      Nausea and Vomiting, Insomnia, and Appetite Loss (p < 0.05). Conclusions. These
      results indicate differences in HRQoL overall and at progression between
      dacarbazine and eribulin patients, with increases in symptom severity observed
      among dacarbazine patients.

PMID- 28512388
TI  - Insufficient Humidification of Respiratory Gases in Patients Who Are Undergoing
      Therapeutic Hypothermia at a Paediatric and Adult Intensive Care Unit.
AB  - For cooled newborn infants, humidifier settings for normothermic condition
      provide excessive gas humidity because absolute humidity at saturation is
      temperature-dependent. To assess humidification of respiratory gases in patients
      who underwent moderate therapeutic hypothermia at a paediatric/adult intensive
      care unit, 6 patients were studied over 9 times. Three humidifier settings, 37
      default (chamber-outlet, 37 degrees C; Y-piece, 40 degrees C), 33.5-theoretical
      (chamber-outlet, 33.5 degrees C; Y-piece, 36.5 degrees C), and 33.5-adjusted
      (optimised setting to achieve saturated vapour at 33.5 degrees C using feedback
      from a thermohygrometer), were tested. Y-piece gas temperature/humidity and the
      incidence of high (>40.6 mg/L) and low (<32.9 mg/L) humidity relative to the
      target level (36.6 mg/L) were assessed. Y-piece gas humidity was 32.0 (26.8
      37.3), 22.7 (16.9-28.6), and 36.9 (35.5-38.3) mg/L {mean (95% confidence
      interval)} for 37-default setting, 33.5-theoretical setting, and 33.5-adjusted
      setting, respectively. High humidity was observed in 1 patient with 37-default
      setting, whereas low humidity was seen in 5 patients with 37-default setting and
      8 patients with 33.5-theoretical setting. With 33.5-adjusted setting, inadequate
      Y-piece humidity was not observed. Potential risks of the default humidifier
      setting for insufficient respiratory gas humidification were highlighted in
      patients cooled at a paediatric/adult intensive care unit. Y-piece gas conditions
      can be controlled to the theoretically optimal level by adjusting the setting
      guided by Y-piece gas temperature/humidity.

PMID- 28512387
TI  - Oncolytic Virus-Based Immunotherapies for Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma is highly refractory cancer which is resistant to
      conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although
      many anticancer drugs have been developed for treating HCC, sorafenib is the only
      effective treatment, but it only prolongs survival duration for about 3 months.
      Recently, oncolytic virotherapy has shown promising results in treating HCCs and
      the effects can be more enhanced by adopting immune modulatory molecules. This
      review discusses the current status of treating HCC and the effective strategy of
      oncolytic virus-based immunotherapy for the treatment of HCCs.

PMID- 28512390
TI  - Cystic Lymphangioma of the Colon: Endoscopic Removal beyond the Frontiers of
      Size.
AB  - Cystic lymphangiomas are benign colonic neoplasms arising from the submucosa.
      Traditionally, endoscopic resection has been described for smaller lesions, while
      surgery is reserved for larger symptomatic lesions. We present a case of a 69
      year-old asymptomatic individual noted to have a cystic lymphangioma of the colon
      measuring 5 cm, which was successfully removed with endoloop endoscopic resection
      without any complications.

PMID- 28512392
TI  - Utility of Glissonean Pedicle Transection for Surgical Treatment of Severe Liver
      Trauma.
AB  - The most common initial strategy for treatment of severe liver trauma is damage
      control in which hemostasis is achieved by perihepatic gauze packing and/or
      vascular embolization. However, we encounter patients in whom this strategy alone
      is not adequate. We have applied the principles of Glissonean pedicle
      transection, a technique that was originally devised to ensure safe and quick
      performance of planned hepatectomy for liver cancer, to 3 cases of severe liver
      trauma. We performed Glissonean pedicle ligation during damage control surgery in
      2 patients and Glissonean pedicle transection during the definitive surgery in 1
      patient. We describe the approaches and our experience with them, including
      operation times and outcomes. From our experience thus far, it seems that 8-12 h
      after the damage control procedure is appropriate for performing the definitive
      surgery. Although there are some problems posed by this strategy and cases to
      which it will not be applicable, the method seems to be particularly useful for
      cases of severe liver trauma in which the damage is extensive and involves the
      Glissonean pedicles near the hepatic hilus. We describe our 3 cases in detail and
      review our experience in light of the available literature.

PMID- 28512393
TI  - Immunoglobulin A Lambda Multiple Myeloma in a Patient with HIV: An Unusual Cause
      of Massive Ascites.
AB  - Multiple myeloma (MM) is a neoplastic proliferation of plasma cells with
      overproduction of monoclonal immunoglobulins and infiltration into the bone and
      other organs. Ascites can develop in patients with lymphoproliferative and solid
      malignancies involving the peritoneum. However, ascites is unusual in MM and
      rarely the initial presenting sign or symptom. The development of ascites can be
      due to peritoneal infiltration or secondary to hepatic involvement, heart
      failure, or kidney failure. Ascites in MM reflects a more aggressive stage, and
      the reported prognosis is poor, with a median survival of 1-2 months. Here we
      present a rare case of immunoglobulin A lambda MM presenting with massive
      myelomatous ascites.

PMID- 28512391
TI  - A Foreign Body (Toothbrush) in the Esophagus of a Patient with Hiatal Hernia.
AB  - Toothbrush ingestion is rare and most commonly seen in patients with psychiatric
      comorbidities and in young women with a medical history of eating disorders who
      try to induce emesis. Long ingested objects, such as a toothbrush, cannot pass
      the gastrointestinal tract spontaneously and require endoscopic removal or even a
      surgical approach in cases of unsuccessful endoscopic removal or complication
      development. We present a case of a 71-year-old male with hiatal hernia without
      psychiatric or neurological comorbidity who accidentally ingested a toothbrush
      during oral hygiene routine. After X-ray confirmation, the toothbrush was removed
      endoscopically.

PMID- 28512394
TI  - Successful Endoscopic Management of Late Biliary Cast Syndrome in a Liver
      Transplant Recipient: A Case Report.
AB  - Biliary cast syndrome (BCS) is an unusual complication of liver transplantation
      (LT). The pathophysiology is not known, and it is thought to develop because of
      mucosal damage in the bile duct related to obstruction, ischemia, or bacterial
      infection. It occurs in 2.5-18% of LT patients and is associated with increased
      graft failure, need for retransplantation, and mortality. Here we report on a
      case of BCS of late appearance after LT who was successfully treated by
      endoscopic means.

PMID- 28512396
TI  - A Generic Transferable EEG Decoder for Online Detection of Error Potential in
      Target Selection.
AB  - Reliable detection of error from electroencephalography (EEG) signals as feedback
      while performing a discrete target selection task across sessions and subjects
      has a huge scope in real-time rehabilitative application of Brain-computer
      Interfacing (BCI). Error Related Potentials (ErrP) are EEG signals which occur
      when the participant observes an erroneous feedback from the system. ErrP holds
      significance in such closed-loop system, as BCI is prone to error and we need an
      effective method of systematic error detection as feedback for correction. In
      this paper, we have proposed a novel scheme for online detection of error
      feedback directly from the EEG signal in a transferable environment (i.e., across
      sessions and across subjects). For this purpose, we have used a P300-speller
      dataset available on a BCI competition website. The task involves the subject to
      select a letter of a word which is followed by a feedback period. The feedback
      period displays the letter selected and, if the selection is wrong, the subject
      perceives it by the generation of ErrP signal. Our proposed system is designed to
      detect ErrP present in the EEG from new independent datasets, not involved in its
      training. Thus, the decoder is trained using EEG features of 16 subjects for
      single-trial classification and tested on 10 independent subjects. The decoder
      designed for this task is an ensemble of linear discriminant analysis, quadratic
      discriminant analysis, and logistic regression classifier. The performance of the
      decoder is evaluated using accuracy, F1-score, and Area Under the Curve metric
      and the results obtained is 73.97, 83.53, and 73.18%, respectively.

PMID- 28512395
TI  - Keypress-Based Musical Preference Is Both Individual and Lawful.
AB  - Musical preference is highly individualized and is an area of active study to
      develop methods for its quantification. Recently, preference-based behavior,
      associated with activity in brain reward circuitry, has been shown to follow
      lawful, quantifiable patterns, despite broad variation across individuals. These
      patterns, observed using a keypress paradigm with visual stimuli, form the basis
      for relative preference theory (RPT). Here, we sought to determine if such
      patterns extend to non-visual domains (i.e., audition) and dynamic stimuli,
      potentially providing a method to supplement psychometric, physiological, and
      neuroimaging approaches to preference quantification. For this study, we adapted
      our keypress paradigm to two sets of stimuli consisting of seventeenth to twenty
      first century western art music (Classical) and twentieth to twenty-first century
      jazz and popular music (Popular). We studied a pilot sample and then a separate
      primary experimental sample with this paradigm, and used iterative mathematical
      modeling to determine if RPT relationships were observed with high R2 fits. We
      further assessed the extent of heterogeneity in the rank ordering of keypress
      based responses across subjects. As expected, individual rank orderings of
      preferences were quite heterogeneous, yet we observed mathematical patterns
      fitting these data similar to those observed previously with visual stimuli.
      These patterns in music preference were recurrent across two cohorts and two
      stimulus sets, and scaled between individual and group data, adhering to the
      requirements for lawfulness. Our findings suggest a general neuroscience
      framework that predicts human approach/avoidance behavior, while also allowing
      for individual differences and the broad diversity of human choices; the
      resulting framework may offer novel approaches to advancing music neuroscience,
      or its applications to medicine and recommendation systems.

PMID- 28512397
TI  - Leukocyte Expression of Type 1 and Type 2 Purinergic Receptors and Pro
      Inflammatory Cytokines during Total Sleep Deprivation and/or Sleep Extension in
      Healthy Subjects.
AB  - The purinergic type P1 (adenosine A1 and A2A) receptors and the type P2 (X7)
      receptor have been suggested to mediate physiological effects of adenosine and
      adenosine triphosphate on sleep. We aimed to determine gene expression of A1R
      (receptor), A2AR, and P2RX7 in leukocytes of healthy subjects during total sleep
      deprivation followed by sleep recovery. Expression of the pro-inflammatory
      cytokines IL-1beta and TNF-alpha were also determined as they have been
      characterized as sleep regulatory substances, via P2RX7 activation. Blood
      sampling was performed on 14 young men (aged 31.9 +/- 3.9) at baseline (B), after
      24 h of sleep deprivation (24 h-SD), and after one night of sleep recovery (R).
      We compared gene expression levels after six nights of habitual (22.30-07.00) or
      extended (21.00-07.00) bedtimes. Using quantitative real-time PCR, the amount of
      mRNA for A1R, A2AR, P2RX7, TNF-alpha, and IL-1beta was analyzed. After 24 h-SD
      compared to B, whatever prior sleep condition, a significant increase of A2AR
      expression was observed that returned to basal level after sleep recovery [day
      main effect, F(2, 26) = 10.8, p < 0.001]. In both sleep condition, a day main
      effect on P2RX7 mRNA was observed [F(2, 26) = 6.7, p = 0.005] with significant
      increases after R compared with 24 h-SD. TNF-alpha and IL-1beta expressions were
      not significantly altered. Before 24 h-SD (baseline), the A2AR expression was
      negatively correlated with the latency of stage 3 sleep during the previous
      night, while that of the A1R positively. This was not observed after sleep
      recovery following 24 h-SD. This is the first study showing increased A2AR and
      not A1 gene expression after 24 h-SD in leukocytes of healthy subjects, and this
      even if bedtime was initially increased by 1.5 h per night for six nights. In
      conclusion, prolonged wakefulness induced an up-regulation of the A2A receptor
      gene expression in leukocytes from healthy subjects. Significant correlations
      between baseline expression of A1 and A2A receptors in peripheral cells and stage
      3 sleep suggested their involvement in mediating the effects of adenosine on
      sleep.

PMID- 28512399
TI  - Protein S Negatively Regulates Neural Stem Cell Self-Renewal through Bmi-1
      Signaling.
AB  - Revealing the molecular mechanisms underlying neural stem cell self-renewal is a
      major goal toward understanding adult brain homeostasis. The self-renewing
      potential of neural stem and progenitor cells (NSPCs) must be tightly regulated
      to maintain brain homeostasis. We recently reported the expression of Protein S
      (PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC
      quiescence and neuronal differentiation. Here, we investigate the effect of PROS1
      on NSPC self-renewal and show that genetic ablation of Pros1 in neural
      progenitors increased NSPC self-renewal by 50%. Mechanistically, we identified
      the upregulation of the polycomb complex protein Bmi-1 and repression of its
      downstream effectors p16Ink4a and p19Arf to promote NSPC self-renewal in Pros1
      ablated cells. Rescuing Pros1 expression restores normal levels of Bmi-1
      signaling, and reverts the proliferation and enhanced self-renewal phenotypes
      observed in Pros1-deleted cells. Our study identifies PROS1 as a novel negative
      regulator of NSPC self-renewal. We conclude PROS1 is instructive for NSPC
      differentiation by negatively regulating Bmi-1 signaling in adult and embryonic
      neural stem cells.

PMID- 28512400
TI  - Exposure to Hedione Increases Reciprocity in Humans.
AB  - Cooperation among unrelated humans is frequently regarded as a defining feature
      in the evolutionary success of our species. Whereas, much research has addressed
      the strategic and cognitive mechanisms that underlie cooperation, investigations
      into chemosensory processes have received very limited research attention. To
      bridge that gap, we build on recent research that has identified the chemically
      synthesized odorant Hedione (HED) as a ligand for the putative human pheromone
      receptor (VN1R1) expressed in the olfactory mucosa, and hypothesize that exposure
      to HED may increase reciprocity. Applying behavioral economics paradigms, the
      present research shows that exposure to the ligand causes differentiated
      behavioral effects in reciprocal punishments (Study 1) as well as rewards (Study
      2), two types of behaviors that are frequently regarded as essential for the
      development and maintenance of cooperation.

PMID- 28512401
TI  - Increased Gamma Connectivity in the Human Prefrontal Cortex during the
      Bereitschaftspotential.
AB  - The Bereitschaftspotential (BP) is a slow negative cortical potential preceding
      voluntary movement. Since movement preparation is dependent upon the synchronous
      activity of a variety of neurons, BP may develop through the exchange of
      information among motor-related neurons. However, the relationship between BP and
      information flow is not yet well-known. In the present study, we aimed to
      investigate how the connectivity in the prefrontal cortex (PFC) changes during
      the occurrence of BP. Electrocorticography (ECoG) was recorded in five patients
      with epilepsy. The subjects performed self-paced hand grasping. We compared the
      intraregional connectivity between PFC and non-PFC regions using partial directed
      coherence. In the PFC, the connectivity of beta and gamma bands in the BP period
      increased by an average of 24.4% compared with the baseline connectivity.
      Conversely, gamma connectivity in non-PFC regions decreased by 31.4%. Moreover,
      the intraregional connectivity in the PFC increased according to the stage of BP.
      The increased gamma band connectivity in the PFC implies that the increased
      communication among neurons in the PFC is associated with development of BP.
      Intraregional connectivity as one of the factors involved in voluntary movement
      may reflect the activation of brain networks related to movement preparation in
      PFC.

PMID- 28512403
TI  - Papulonodular Secondary Syphilis Presenting as Multiple Distinct Cutaneous
      Lesions in an HIV-Positive Transgender Woman.
AB  - We present the first reported case of papulonodular secondary syphilis in an HIV
      positive transgender female. Syphilis is classified into primary, secondary,
      latent, and tertiary stages, with secondary syphilis having notably diverse
      cutaneous manifestations. Our patient presented with diverse lesions throughout
      her body, all pathologically consistent with papulonodular secondary syphilis.
      Proper identification of the multiple presentations of syphilis is crucial to
      early diagnosis and treatment. This report seeks to broaden the scope of
      dermatological manifestations that arise secondary to papulonodular syphilis in
      HIV-positive patients.

PMID- 28512402
TI  - Unilateral Linear Punctate Palmoplantar Keratoderma: A Case Report.
AB  - Punctate palmoplantar keratoderma (PPPK) is a rare entity with an estimated
      prevalence rate of 1.17/100,000. PPPK usually presents with bilateral
      asymptomatic, tiny, hyperkeratotic punctate papules and plaques on the
      palmoplantar surface. Among the PPPK varieties, the linear presentation is much
      rarer, and so far there have been only 3 case reports. Here, we report the case
      of a 27-year-old female Thai patient who presented to our outpatient clinic with
      unilateral asymptomatic linear thickening lesions on her right sole since
      childhood. There were no similar lesions on other parts of the body. A
      histopathologic examination revealed epidermal hyperplasia and hyperkeratosis
      without columns of parakeratosis or cornoid lamella. The other examinations were
      normal. The clinical and histological contexts were consistent with a diagnosis
      of unilateral linear PPPK. The patient was treated with topical 10% urea cream
      and 10% salicylic acid cream twice daily. To the best of our knowledge, this is
      the first reported case of unilateral linear PPPK in Thailand, and the fourth
      reported case worldwide.

PMID- 28512404
TI  - Painful Leg Ulceration in a Poorly Controlled Hypertensive Patient: A Case Report
      of Martorell Ulcer.
AB  - Martorell ulcer is a form of lower limb ulceration, preceded by a small area of
      excruciating pain. It often appears as a solitary lesion on the outer aspect of
      the lower limb, and is primarily associated with poorly controlled hypertension
      and diabetes. Treatment of the ulcer involves awareness and early correct
      diagnosis, adequate control of blood pressure, management of infection, and wound
      care. We describe a 77-year-old diabetic and hypertensive woman presenting with
      excruciating pain in her right lower lateral leg leading to a necrotic ulcer.
      Serial photographs of the evolution of the lesion and eventual healing of the
      ulcer are presented.

PMID- 28512398
TI  - Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
AB  - Protein homeostasis (proteostasis), the correct balance between production and
      degradation of proteins, is essential for the health and survival of cells.
      Proteostasis requires an intricate network of protein quality control pathways
      (the proteostasis network) that work to prevent protein aggregation and maintain
      proteome health throughout the lifespan of the cell. Collapse of proteostasis has
      been implicated in the etiology of a number of neurodegenerative diseases,
      including amyotrophic lateral sclerosis (ALS), the most common adult onset motor
      neuron disorder. Here, we review the evidence linking dysfunctional proteostasis
      to the etiology of ALS and discuss how ALS-associated insults affect the
      proteostasis network. Finally, we discuss the potential therapeutic benefit of
      proteostasis network modulation in ALS.

PMID- 28512406
TI  - A Case of Subcutaneous Sarcoidosis Occurring along the Superficial Veins of the
      Forearms: A Distinctive Cutaneous Manifestation Masquerading Venous Tropic Action
      in the Underlying Systemic Disease?
AB  - Sarcoidosis is a multisystem disease of unknown etiology, developing granulomas
      in any tissues and organs. Approximately 25% of sarcoidosis patients have
      cutaneous involvement with various clinical manifestations, which are categorized
      into specific or nonspecific diseases based on the histopathology; the former
      represents the typical sarcoid granulomas. Subcutaneous sarcoidosis is one of the
      specific skin lesions and often affects extremities, to a much lesser extent with
      other anatomical sites. Herein, we report the case of an 82-year-old Japanese man
      with subcutaneous sarcoidosis whose skin nodules exclusively overlay the lines of
      superficial veins on the forearms. This rare clinical presentation was discussed
      with the literature reported thus far to access the underlying disease
      pathophysiology from the viewpoint of tropic response to the venous system in
      systemic sarcoidosis.

PMID- 28512405
TI  - Concomitant B Hairy Cell Leukemia and Mycosis Fungoides in an Elderly Man.
AB  - The development of both a T- and B-cell lymphoproliferative disorder in one
      patient is an unlikely coincidence due to the low prevalence of each malignancy.
      We report a 65-year-old man with a previously documented history of B hairy cell
      leukemia, who presented with a new-onset acneiform eruption of his scalp, face,
      trunk, back, and extremities. Routine pathology of the skin lesions with
      immunohistochemical stains and molecular studies were consistent with a
      folliculotropic mycosis fungoides. B hairy cell leukemia and mycosis fungoides
      occurring in the same patient seems to be a rare phenomenon with only 5 cases
      reported in the literature.

PMID- 28512407
TI  - Severe Rhabdomyolysis during Treatment with Trabectedin in Combination with a
      Herbal Drug in a Patient with Metastatic Synovial Sarcoma: A Case Report.
AB  - Rhabdomyolysis is defined as dissolution of striped muscle characterized by
      leakage of intracellular muscle components into the circulation, which can
      ultimately lead to renal failure with a possible fatal outcome. This is an
      uncommon side effect of trabectedin which is used in second-line therapy of
      metastatic sarcoma after anthracycline and ifosfamide failure. Here, we describe
      a case of reversible rhabdomyolysis in a male patient with recurrent metastatic
      synovial sarcoma of the hand, with marked 18F-FDG uptake into his skeletal
      muscles, after 4 cycles of trabectedin, and who at the same time was taking an
      alternative medicine (bioflavonoids) suspected of triggering this adverse event.

PMID- 28512408
TI  - Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy for
      Recurrent Ovarian Cancer with Incidental Bochdalek Hernia and Postoperative
      Bilateral Thalamic Infarct: A Case Report.
AB  - Congenital Bochdalek hernia is a defect of the diaphragm and very rare in adults.
      Only around 100 cases have been reported in the literature. Herein, we present a
      case with a recurrent ovarian cancer who underwent secondary cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy. An oval defect with
      dimensions of 3 * 4 cm was seen in the left posterolateral site of the diaphragm
      during surgical exploration. In addition, a 6 * 3 cm iatrogenic right-sided
      diaphragmatic defect was found and repaired. In the early postoperative period, a
      bilateral thalamic infarction occurred.

PMID- 28512409
TI  - Immunoglobulin D Multiple Myeloma Presenting as Spontaneous Fracture.
AB  - Immunoglobulin D multiple myeloma is a rare type of multiple myeloma that usually
      presents as bone pain, fatigue, or weight loss. We report a case of
      immunoglobulin D multiple myeloma in a 53-year-old Caucasian male patient with
      previous medical history of anaplastic oligodendroglioma status post-surgical
      resection who was evaluated for back pain while mowing the lawn. His physical
      examination showed tenderness over the lower thoracic vertebrae with no sensory
      or motor impairment. Initial lab investigations showed normocytic anemia and
      hypercalcemia with low parathyroid hormone. Magnetic resonance imaging of
      thoracic spine with and without contrast showed acute pathological fracture of
      the T12 vertebral body with enhancing soft tissue which extended into the left
      ventral epidural space and left T11-T12 neural foramen. Serum protein
      electrophoresis showed abnormal protein band in the gamma globulin. Free light
      chain assay showed serum free kappa which was elevated at 3,090.0 mg/L (reference
      range 3.3-19.4 mg/L). Immunoglobulin D was elevated at 566.0 mg/dL (reference
      range <15.3 mg/dL). The patient was successfully treated with standard
      chemotherapy and autologous peripheral blood stem cell transplant with complete
      remission 3 years after starting treatment. Advancement in the treatment of
      immunoglobulin D multiple myeloma urge clinicians to offer their patients new
      treatment options especially as of the earlier presentation of this subtype of
      multiple myeloma and the previous reports of worse prognosis.

PMID- 28512411
TI  - Spinal Intradural Intramedullary Dissemination in the Absence of Intracranial
      Relapse of a Previously Radically Treated Temporal Lobe Glioblastoma Multiforme.
AB  - Intracranial glioblastoma multiforme (GBM) constitutes the most frequent and
      unfortunately aggressive primary central nervous system malignancy. Despite the
      high tendency of these tumors to show local relapse within the brain after
      primary therapy, dissemination into the spinal axis is an infrequent event. If
      spinal metastases occur they are leptomeningeal in the vast majority of cases and
      always in the context of intracranial progressive disease. Spinal intramedullary
      metastases of intracranial GBM have rarely been described to date. We report the
      unique case of a young woman with subacute progressive paraparesis due to spinal
      intramedullary metastases of a temporal lobe GBM despite the remarkable absence
      of intracranial tumor relapse. The patient had undergone gross total resection of
      a left temporal GBM in contact with the ventricles and cisternal space followed
      by radio- and chemotherapy 13 months before. At the moment of diagnosis of spinal
      intramedullary metastases, there were no signs of intracranial tumor recurrence
      as revealed by MRI scans. Since a high level of suspicion may be needed to detect
      this rare evolution of intracranial GBM and other differential diagnoses must be
      ruled out at presentation, we discuss the important features of this case
      regarding clinical manifestation, diagnosis, surgery, and management.
      Furthermore, we mention possible factors that may have contributed to the
      development of these metastases in the context of intracranial remission.

PMID- 28512412
TI  - Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another
      Metastatic Lesion in Malignant Melanoma Patients.
AB  - Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the
      Food and Drug Administration as a treatment option for patients with unresectable
      melanoma without brain metastasis. In the literature, vemurafenib has been
      reported to be also effective against brain metastasis. We encountered 3 cases
      with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was
      clinically effective against metastatic lesions other than those in the brain.
      The brain lesions developed after the metastatic lesion had occurred. Therefore,
      we assume that the melanomas of the patients acquired resistance against
      vemurafenib. The brain metastases were treated with the cyberknife. Patients 1
      and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH
      elevation died despite the treatment. We need to carefully follow patients on
      vemurafenib therapy because brain metastasis can suddenly occur even if the
      metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib
      against brain metastasis is poor in cases with LDH elevation.

PMID- 28512410
TI  - RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of
      the Vagina: A Rare Gynecological Tumor.
AB  - Small cell carcinoma of the vagina is rare, so rare in fact that the total number
      reported in English-language journals is less than 30. Due to this extremely low
      incidence, no specific treatment guidelines have been established, and most of
      what is clinically known is derived from a handful of single case reports.
      However, as befitting its highly aggressive histologic features, which are
      reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled
      after SCLC. Herein is reported the case of a 51-year-old African-American patient
      with metastatic biopsy-proven small cell carcinoma of the vagina that progressed
      through multiple therapies: first-line cisplatin and etoposide (making it
      platinum-resistant) and radiotherapy, followed by the tumor macrophage
      stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per
      protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST
      v.1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied
      by central necrosis in several of the enlarged lymph nodes and hepatic
      metastases, which may have been evidence of pseudoprogression, accounting for her
      ongoing longer-than-expected survival, since the necrotic tissue may have primed
      the activity of the PD-1 inhibitor. The lack of response to RRx-001 is
      hypothesized to have correlated with sparse tumor macrophage infiltration, seen
      on pre- and post-treatment biopsies, since the mechanism of action of RRx-001
      relates to stimulation of tumor-associated macrophages.

PMID- 28512413
TI  - Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related
      Adverse Events.
AB  - Nivolumab is a recently approved medication for the treatment of unresectable
      malignant melanoma. Many immune-related adverse events (irAEs) associated with
      nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and
      thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how
      or if nivolumab should be administered to patients after they have experienced an
      irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1
      demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2
      had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest
      shadow of CT scan in both cases. However, when nivolumab was re-administrated,
      case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From
      our cases, it is difficult to re-administrate nivolumab for the patients with
      pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve
      their symptoms.

PMID- 28512414
TI  - An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively
      Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor.
AB  - A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound
      performed for a medical check-up. Abdominal contrast-enhanced computed tomography
      showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail.
      Endoscopic ultrasound-guided fine needle aspiration was performed. An
      extragastric growing gastrointestinal stromal tumor was thereby diagnosed
      preoperatively, and surgical resection was planned. Laparoscopic surgery was
      attempted but conversion to open surgery was necessitated by extensive adhesions,
      and distal pancreatectomy, splenectomy, and partial gastrectomy were performed.
      The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor
      is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic
      tissues. It usually occurs in the extremities and abdominal wall, and only rarely
      in the abdominal cavity. We experienced a case with an intra-abdominal desmoid
      tumor that was histologically diagnosed after laparotomy, which had been
      preoperatively diagnosed as an extragastric growing gastrointestinal stromal
      tumor. Although rare, desmoid tumors should be considered in the differential
      diagnosis of intra-abdominal tumors. Herein, we report this case with a
      literature review.

PMID- 28512415
TI  - Neoadjuvant Chemotherapy and Adjuvant Chemoradiation Therapy in the Treatment of
      Resected Gastric Adenocarcinoma: A Case Series.
AB  - The treatment of gastric cancer requires a multimodal approach to decrease the
      risk of locoregional and distant recurrence. The optimal timing of chemotherapy,
      surgery, and radiation therapy continues to be explored in ongoing trials. In the
      United States, surgical resection is often followed by adjuvant chemoradiation
      therapy or by a combination of neoadjuvant and adjuvant chemotherapy. Here we
      report on 4 patients with resected gastric adenocarcinoma who were treated with a
      combination of these 2 approaches, receiving neoadjuvant chemotherapy followed by
      adjuvant chemoradiation therapy.

PMID- 28512417
TI  - A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic
      Hyperosmolar Nonketotic Syndrome.
AB  - Carcinoid tumors are neuroendocrine tumors that mainly arise in the
      gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been
      associated with Cushing syndrome, which results from ectopic adrenocorticotrophic
      hormone (ACTH) secretion. We report the case of a 65-year-old man, a colonel in
      the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a
      clinical trial who was hospitalized for complaints of increasing thirst,
      polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia
      suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS).
      Additional findings, which included hypokalemia, hypernatremia, hypertension,
      metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic
      ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a
      fluid replacement and insulin drip resulted in immediate symptomatic improvement.
      Cushing syndrome should be considered in carcinoid patients with physical
      stigmata such as moon facies and striae. HHNS may be the presenting clinical
      feature in patients with impaired glucose metabolism.

PMID- 28512416
TI  - Unusual Case of Laryngeal Squamous Cell Carcinoma with Cervical Metastasis of a
      Prostatic Adenocarcinoma: A Case Report.
AB  - Brain and Head and neck metastases are rare in prostatic carcinoma patients. In
      this report we present a very uncommon case of the concomitant occurrence of a
      prostatic adenocarcinoma with neck metastases and an advanced laryngeal squamous
      cell carcinoma without neck metastases. The presence of cervical lymph node
      prostate adenocarcinoma metastasis concomitantly with a laryngeal squamous cell
      carcinoma is at least intriguing and may remind us of a rare event called
      "collision tumors". In this case we had the metastatization of 1 carcinoma to the
      site of the drainage of another carcinoma, but we never found the 2 histological
      types as close as requested to reach the definition of a collision tumor. This
      emphasizes the need of histological verification of different sites of recurrence
      when 2 or more primary cancers are known in a patient, particularly when the
      treatments of those primary cancers vary widely.

PMID- 28512418
TI  - Cushing's Syndrome, Cortisol, and Cognitive Competency: A Case Report.
AB  - Glucocorticoids are associated with immunosuppression and neuropsychiatric
      complications. We describe the case of a carcinoid patient with Cushing's
      syndrome (CS) and neurocognitive impairment due to ectopic ACTH production who
      developed sepsis and died because of his family's decision to withdraw antibiotic
      treatment. This report is presented to illustrate the importance of advanced-care
      planning in patients with CS.

PMID- 28512419
TI  - Successful Treatment of Primary Cutaneous Peripheral T-Cell Lymphoma Presenting
      Acquired Ichthyosis with Oral Bexarotene Monotherapy.
AB  - Acquired ichthyosis (AI) is a reactive cutaneous manifestation that can be
      associated with malignant hematological disease, including cutaneous T-cell
      lymphoma (CTCL). Since it is difficult to distinguish AI from ichthyosiform
      mycosis fungoides, to select the treatment for CTCL with ichthyosis-like
      appearance and to evaluate its efficacy is sometimes challenging. In this report,
      we describe a case of primary cutaneous peripheral T-cell lymphoma not otherwise
      specified presenting AI successfully treated with oral bexarotene. In the present
      case, the administration of oral bexarotene was not only effective for lymphoma
      cells infiltrating ulcers and nodules, but it also eliminated AI.

PMID- 28512420
TI  - A Case of Iris Melanocytoma Demonstrating Diffuse Melanocytic Proliferation with
      Uncontrolled Intraocular Pressure.
AB  - We report a rare case with histologically proven melanocytoma of the iris that
      demonstrated diffuse melanocytic proliferation with uncontrolled secondary
      glaucoma and investigate the etiology of the intraocular pressure elevation. The
      patient was a 78-year-old man with a history of darkened iris of his left eye.
      The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse
      darkened iris, and a gonioscopic examination revealed open angle with
      circumferential heavy pigmentation. There was no pigment dispersion of the
      anterior chamber and no pigment deposition of the cornea. We suspected malignant
      ring melanoma in the left eye and enucleated it. The globe was examined with
      light and electron microscopy. Light microscopy revealed the presence of heavily
      pigmented tumor cells in the iris, ciliary body, trabecular meshwork, and
      Schlemm's canal. A bleached preparation showed large tumor cells with central and
      paracentral nuclei without mitosis. Electron microscopy of the trabecular
      meshwork revealed melanin-bearing tumor cells invading the intertrabecular
      spaces, and the melanin granules were not phagocytosed in the trabecular cells.
      The mechanical obstruction of the aqueous flow by the tumor cells may be a major
      cause of secondary glaucoma in eyes with iris melanocytoma presenting diffuse
      proliferation.

PMID- 28512421
TI  - When an Easy Thing Goes Wrong: Foreign Body Induced Granuloma-Associated
      Scleritis Following Pterygium Surgery.
AB  - PURPOSE: To report a case of pterygium surgery with conjunctival autograft
      followed by focal necrotizing scleritis due to foreign body entrapment in the
      scleral bed. CASE REPORT/RESULTS: This is a case report of a 76-years-old male
      patient who underwent nasal pterygium surgery and developed focal necrotizing
      scleritis secondary to foreign body entrapment under conjunctival autograft. One
      month following surgery, slit-lamp examination demonstrated a progressive
      thinning of the surgical area with focal inflammatory signs. A small synthetic
      fiber was identified to be trapped under the graft. A second intervention was
      performed with foreign body removal and a new conjunctival graft. Despite the
      surgery, focal scleral melting continued to progress and the patient was placed
      under systemic corticotherapy and submitted to amniotic membrane graft with
      epithelial side up. During the follow-up period there was a good tissue response.
      CONCLUSION: Despite being a safe and quick procedure, pterygium surgery can
      sometimes elicit new challenges.

PMID- 28512422
TI  - Acute Onset Ocular Hypotony after Coronary Artery Bypass Surgery.
AB  - IMPORTANCE: The purpose of this case report is to evaluate risk factors
      associated with post-coronary artery bypass graft (CABG) ocular hypotony compared
      to post-CABG ischemic optic neuropathy. OBSERVATIONS: The patient described here
      is a single case at the University of California, Irvine Medical Center, from
      July 2016. This case demonstrates the rare incidence of acute post-CABG ocular
      hypotony and vision loss in a patient with prior history of optic atrophy. Both
      vision loss and hypotony resolved completely to baseline without intervention
      within 3 days postoperatively. CONCLUSIONS AND RELEVANCE: Severe anemia and large
      fluctuations in central venous pressure and blood pressure can occur in any
      patient undergoing CABG surgery. These hemodynamic shifts can cause transient
      ischemia to pressure controlling systems such as the ciliary body and reduce
      episcleral venous pressure. Other risk factors for acute hypotony in the setting
      of CABG surgery also include the use of hypertonic agents, cardiopulmonary
      bypass, and intravenous anesthesia.

PMID- 28512423
TI  - Refined Internal Limiting Membrane Inverted Flap Technique for Intractable
      Macular Detachment with Optic Disc Pit.
AB  - PURPOSE: To report a surgical technique for retinal detachment associated with
      optic disc pit (ODP) by using an internal limiting membrane (ILM) inverted flap
      as an obstacle between the vitreous cavity and subretinal space. CASE
      PRESENTATION: A 43-year-old man presented with decreased visual acuity in the
      right eye for 1 week due to macular detachment associated with ODP. After 2
      unsuccessful surgeries, the retina was reattached by vitrectomy with an ILM
      inverted flap onto the ODP. CONCLUSION: Covering the pit with an inverted ILM
      flap is a reliable method for intercepting fluid from the vitreous cavity.
      Immediate absorption of subretinal fluid may lead to early macular attachment.
      This technique would be effective in managing ODP.

PMID- 28512424
TI  - Optical Coherence Tomography Angiography of Retinal Microvascular Changes
      Overlying Choroidal Nodules in Neurofibromatosis Type 1.
AB  - PURPOSE: To report 3 cases of neurofibromatosis type 1 (NF1) with choroidal
      nodules associated with retinal microvascular changes imaged with optical
      coherence tomography angiography (OCTA). METHODS: Small case series in 3 NF1
      patients. OCTA examinations were performed by a trained examiner (J.J.) after
      pupillary dilation. A standard scan, centered over the macula measuring 6 * 6 mm
      and 3 * 3 mm was obtained according to the findings on standard color
      photography. Additional scans were obtained in the zones with microvascular
      abnormalities. The segmentation provided by the machine software was used.
      RESULTS: Corkscrew retinal vessels were observed in association with "placoid"
      type choroidal nodules as shown by near-infrared reflectance imaging. In all
      cases, multiple lesions were found. They were second- or third-order tortuous
      vessels originating from the superior or inferior temporal veins. OCTA
      demonstrated that the tortuous venules were located in the superficial capillary
      plexus, and no abnormalities were found in the deep capillary plexus. DISCUSSION:
      Corkscrew retinal vessels are part of a spectrum of retinal microvascular
      alterations seen in association, sometimes overlying choroidal nodules in
      patients with NF1 and are visualized in the superficial capillary plexus on OCTA.
      We demonstrated with OCTA that they are not associated with flow loss or ischemia
      in the superficial and deep capillary plexus. The link between the underlying
      nodule remains unclear. Since neovascularization was described in choroidal
      ganglioneuroma, we hypothesize that corresponding secretory substances from
      Schwann cells, ganglion cells, or melanocytes in choroidal nodules might alter
      the retinal vasculature. CONCLUSION: We report on 3 cases of NF1 with choroidal
      nodules in association with retinal microvascular changes imaged with OCTA. OCTA
      demonstrated preservation of the blood flow in the deep and superficial capillary
      plexus of the retina. We hypothesize that angiogenic factors secreted by the
      underlying choroidal nodules could have an effect on the retinal vasculature.
      Further immunohistological studies in NF1 patients with choroidal nodules to
      detect angiogenic factors (such as VEGF) are necessary to confirm this
      hypothesis.

PMID- 28512425
TI  - Long-Term Follow-Up of Polypoidal Choroidal Vasculopathy Secondary to Angioid
      Streaks Treated by Intravitreal Aflibercept and Ranibizumab.
AB  - PURPOSE: Angioid streaks (AS) are dehiscences in Bruch's membrane that may be
      idiopathic or associated with numerous systemic illnesses. Polypoidal choroidal
      vasculopathy (PCV) is an underdiagnosed exudative chorioretinopathy often
      characterised by serosanguineous detachments of the pigmented epithelium. The use
      of the anti-VEGF agents ranibizumab and aflibercept in the management of PCV
      secondary to AS has not been previously documented. We report 3 patients with
      active PCV secondary to AS, 1 of which had a family history of PCV secondary to
      AS, not previously reported in the literature. All patients were symptomatic and
      treated with intravitreal anti-VEGF therapy with and without combination
      photodynamic therapy (PDT). METHODS: This is a long-term retrospective case
      review of 3 eyes of 3 patients with AS and clinical features of PCV. The patients
      were examined using fundoscopy, spectral domain optical coherence tomography,
      fluorescein angiography, and indocyanine green angiography. All patients were
      managed with intravitreal anti-VEGF using a treat-and-extend protocol according
      to specific retreatment criteria. One patient had 1 session of PDT in combination
      with anti-VEGF injections. RESULTS: The mean follow-up time in all patients was 4
      years. In all 3 cases, the treatment resulted in improved visual acuity and
      regression of active PCV lesions with a longer duration between injections.
      CONCLUSION: The treat-and-extend protocol with intravitreal aflibercept or
      ranibizumab with or without PDT is effective and safe for PCV secondary to AS.

PMID- 28512426
TI  - Spontaneous Unilateral Subperiosteal Hematoma in the Orbit due to Self-Induced
      Asphyxia: Unusual Cause of Unilateral Exophthalmos.
AB  - BACKGROUND: To report an unusual case of subperiosteal bleeding of nontraumatic
      etiology. CASE DESCRIPTION: A 48-year-old female presented with an acute
      protrusion of the left eye after nonaccomplished suicide by means of asphyxia
      using a cable around the neck. At the time of presentation, the MRI showed an
      orbital subperiosteal hematoma causing an exophthalmos. After conservative
      treatment, there was a complete remission of the lesion. CONCLUSION: Nontraumatic
      subperiosteal bleedings without involvement of the intraocular structures and no
      vision-threatening intraorbital changes should be treated conservatively.

PMID- 28512427
TI  - Long-Term Clinical Course in a Patient with Complete Congenital Stationary Night
      Blindness.
AB  - BACKGROUND: This report describes a 45-year-old man with complete congenital
      stationary night blindness (CSNB1) who has been followed up for 38 years. CASE:
      The patient first visited our hospital as a 7-year-old boy with a complaint of
      low visual acuity. Best corrected visual acuity (BCVA) was 0.5 in the right eye
      and 0.6 in the left eye. The refractive error was approximately -5.0 D in both
      eyes. The fundus showed only myopic changes. A bright-flash electroretinogram
      (ERG) revealed a negative configuration. We diagnosed CSNB and corrected the
      refractive error with glasses. We continued to monitor the ERG and various
      waveform components as well as visual acuity and the appearance of the fundus.
      All NYX exons were screened for a causative mutation by polymerase chain reaction
      amplification, and direct sequencing was performed. RESULTS: By 10 years of age,
      BCVA had increased to 0.8 on the right and 0.9 on the left, with little change
      thereafter. The fundus continued to show only myopic changes. No changes were
      seen in the amplitude or implicit time of the a-wave or b-wave or in the b/a-wave
      ratio. A novel hemizygous insertion mutation, c.1205_1206insT,
      p.(Glu404Argfs*89), was detected in exon 2 of the NYX gene. CONCLUSION: To our
      knowledge, this is the longest follow-up of a patient with CSNB1. No changes in
      the clinical course have been seen during follow-up. We believe that it is
      important to continue observations and accumulate clinical data for prognostic
      purposes on patients with CSNB1.

PMID- 28512428
TI  - Type 3 Neovascularization Associated with Retinitis Pigmentosa.
AB  - PURPOSE: To report a case of type 3 neovascular lesion in a patient with
      retinitis pigmentosa (RP) complicated by macular edema. CASE REPORT: A 78-year
      old man with a long follow-up for RP was referred for painless visual acuity
      decrease in the right eye. Best-corrected visual acuity was 20/125 in the right
      eye and 20/40 in the left. Fundus examination showed typical RP and macular edema
      in both eyes. In the right eye, spectral domain optical coherence tomography
      revealed a marked cystic macular edema associated with disruption of the Bruch
      membrane/retinal pigment epithelium complex overlying a pigmentary epithelium
      detachment, with a vascular structure which appeared to originate from the deep
      capillary plexus and to be connected with the subretinal pigment epithelium
      space. Optical coherence tomography angiography showed a high-flow vessel
      infiltrating the outer retinal layers in the deep capillary plexus segmentation,
      and a tuft-shaped, bright, high-flow network that seemed to be connected with the
      subretinal pigment epithelium space in the outer retinal layer segmentation. This
      presentation was consistent with an early type 3 neovascular lesion in the right
      eye. CONCLUSION: Type 3 neovascularization may be considered a possible
      complication of RP.

PMID- 28512429
TI  - Reduced Prefrontal Short-Latency Afferent Inhibition in Older Adults and Its
      Relation to Executive Function: A TMS-EEG Study.
AB  - Combining transcranial magnetic stimulation (TMS) with electroencephalography
      (EEG) allows for the assessment of various neurophysiological processes in the
      human cortex. One of these paradigms, short-latency afferent inhibition (SAI), is
      thought to be a sensitive measure of cholinergic activity. In a previous study,
      we demonstrated the temporal pattern of this paradigm from both the motor (M1)
      and dorsolateral prefrontal cortex (DLPFC) using simultaneous TMS-EEG recording.
      The SAI paradigm led to marked modulations at N100. In this study, we aimed to
      investigate the age-related effects on TMS-evoked potentials (TEPs) with the SAI
      from M1 and the DLPFC in younger (18-59 years old) and older (>=60 years old)
      participants. Older participants showed significantly lower N100 modulation in M1
      SAI as well as DLPFC-SAI compared to the younger participants. Furthermore, the
      modulation of N100 by DLPFC-SAI in the older participants correlated with
      executive function as measured with the Trail making test. This paradigm has the
      potential to non-invasively identify cholinergic changes in cortical regions
      related to cognition in older participants.

PMID- 28512430
TI  - CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the
      Impact of CYP2D6*10 on Interindividual Variation in a Chinese Population.
AB  - Purpose: Asian populations have around 40-60% frequency of reduced function
      allele CYP2D6*10 compared to 1-2% in Caucasian populations. The wide range of
      CYP2D6 enzyme activities in subjects with the CYP2D6*10 variant is a big concern
      for clinical practice. The quantitative analysis measuring the impact of CYP2D6
      enzyme activity as a result of one CYP2D6*10 allele or two CYP2D6*10 alleles has
      not been reported in large Asian populations. Methods: A total of 421 healthy
      Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and
      direct DNA sequencing. A total of 235 subjects with CYP2D6*1/*1 (n = 22),
      CYP2D6*1/*10 (n = 93), CYP2D6*10/*10 (n = 85), and CYP2D6*5/*10 (n = 35) were
      phenotyped for CYP2D6 using dextromethorphan as the probe drug. Metabolic ratios
      (MR) were calculated as the ratio of parent drug to metabolite in 0-3 h urine, 3
      h plasma, and 3 h saliva for each sample type. Results: The urinary, plasma, or
      salivary MRs increased successively in subjects with CYP2D6*1/*1, *1/*10,
      *10/*10, and *5/*10 (all P < 0.001). In the normal metabolizer group, homozygous
      CYP2D6*10/*10 decreased the CYP2D6 enzyme activity further than heterozygous
      CYP2D6*1/*10. Urinary, plasma, and salivary MRs were highly correlated.
      Conclusion: The normal metabolizer group calls for a more detailed
      classification. The activity score system could more accurately predict enzyme
      activity than by grouping a number of genotypes into a single phenotype group.
      Single-point plasma samples and saliva samples could be used as alternative
      phenotyping methods for clinical convenience.

PMID- 28512431
TI  - Variable Ventilation Improved Respiratory System Mechanics and Ameliorated
      Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion.
AB  - Lung ischemia-reperfusion injury remains a major complication after lung
      transplantation. Variable ventilation (VV) has been shown to improve respiratory
      function and reduce pulmonary histological damage compared to protective volume
      controlled ventilation (VCV) in different models of lung injury induced by
      endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However,
      no study has compared the biological impact of VV vs. VCV in lung ischemia
      reperfusion injury, which has a complex pathophysiology different from that of
      other experimental models. Thirty-six animals were randomly assigned to one of
      two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was
      completely occluded and released after 30 min; and (2) Sham, in which animals
      underwent the same surgical manipulation but without hilar clamping. Immediately
      after surgery, the left (IR-injured) and right (contralateral) lungs from 6
      animals per group were removed, and served as non-ventilated group (NV) for
      molecular biology analysis. IR and Sham groups were further randomized to one of
      two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg,
      positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired oxygen
      (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence
      of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30%
      coefficient of variation. After 5 min of ventilation and at the end of a 2-h
      period (Final), respiratory system mechanics and arterial blood gases were
      measured. At Final, lungs were removed for histological and molecular biology
      analyses. Respiratory system elastance and alveolar collapse were lower in VCV
      than VV (mean +/- SD, VCV 3.6 +/- 1.3 cmH20/ml and 2.0 +/- 0.8 cmH20/ml, p =
      0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8],
      p = 0.04, respectively). In left lungs of IR animals, VCV increased the
      expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV,
      with no significant differences between VV and NV. Compared to VCV, VV increased
      the expression of surfactant protein-D, suggesting protection from type II
      epithelial cell damage. In conclusion, in this experimental lung ischemia
      reperfusion model, VV improved respiratory system elastance and reduced lung
      damage compared to VCV.

PMID- 28512432
TI  - Whole-Body Cryotherapy in Athletes: From Therapy to Stimulation. An Updated
      Review of the Literature.
AB  - Nowadays, whole-body cryotherapy is a medical physical treatment widely used in
      sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season
      recovery are the main purposes for application. However, the most recent studies
      confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this
      therapy by highlighting the underlying physiological responses. In addition to
      its therapeutic effects, whole-body cryotherapy has been demonstrated to be a
      preventive strategy against the deleterious effects of exercise-induced
      inflammation and soreness. Novel findings have stressed the importance of fat
      mass on cooling effectiveness and of the starting fitness level on the final
      result. Exposure to the cryotherapy somehow mimics exercise, since it affects
      myokines expression in an exercise-like fashion, thus opening another possible
      window on the therapeutic strategies for metabolic diseases such as obesity and
      type 2 diabetes. From a biochemical point of view, whole-body cryotherapy not
      always induces appreciable modifications, but the final clinical output (in terms
      of pain, soreness, stress, and post-exercise recovery) is very often improved
      compared to either the starting condition or the untreated matched group. Also,
      the number and the frequency of sessions that should be applied in order to
      obtain the best therapeutic results have been deeply investigated in the last
      years. In this article, we reviewed the most recent literature, from 2010 until
      present, in order to give the most updated insight into this therapeutic
      strategy, whose rapidly increasing use is not always based on scientific
      assumptions and safety standards.

PMID- 28512433
TI  - Reported Hydration Beliefs and Behaviors without Effect on Plasma Sodium in
      Endurance Athletes.
AB  - Purpose: Little information is available on the association of hydration beliefs
      and behaviors in endurance athletes and exercise-associated hyponatremia (EAH).
      The aim of the present study was to determine hydration beliefs and behaviors in
      endurance athletes. Method: A 100 and 38 recreational athletes [107 mountain
      bikers (MTBers) and 31 runners] competing in seven different endurance and ultra
      endurance races completed pre- and post-race questionnaires, and a subgroup of
      113 (82%) participants (82 MTBers and 31 runners) also provided their blood
      samples. Result: More than half of the participants had some pre-race (59%), mid
      race (58%), and post-race (55%) drinking plan. However, the participants
      simultaneously reported that temperature (66%), thirst (52%), and plan (37%)
      affected their drinking behavior during the race. More experienced (years of
      active sport: p = 0.002; number of completed races: p < 0.026) and trained (p =
      0.024) athletes with better race performance (p = 0.026) showed a more profound
      knowledge of EAH, nevertheless, this did not influence their planned hydration,
      reported fluid intake, or post-race plasma sodium. Thirteen (12%) hyponatremic
      participants did not differ in their hydration beliefs, race behaviors, or
      reported fluid intake from those without post-race EAH. Compared to MTBers,
      runners more often reported knowledge of the volumes of drinks offered at fluid
      stations (p < 0.001) and information on how much to drink pre-race (p < 0.001),
      yet this was not associated with having a drinking plan (p > 0.05). MTBers with
      hydration information planned more than other MTBers (p = 0.004). In comparison
      with runners, more MTBers reported riding with their own fluids (p < 0.001) and
      planning to drink at fluid stations (p = 0.003). On the whole, hydration
      information was positively associated with hydration planning (n = 138) (p =
      0.003); nevertheless, the actual reported fluid intake did not differ between the
      group with and without hydration information, or with and without a pre-race
      drinking plan (p > 0.05). Conclusion: In summary, hydration beliefs and behaviors
      in the endurance athletes do not appear to affect the development of asymptomatic
      EAH.

PMID- 28512434
TI  - Evaluation of a Rapid Anisotropic Model for ECG Simulation.
AB  - State-of-the-art cardiac electrophysiology models that are able to deliver
      physiologically motivated activation maps and electrocardiograms (ECGs) can only
      be solved on high-performance computing architectures. This makes it nearly
      impossible to adopt such models in clinical practice. ECG imaging tools typically
      rely on simplified models, but these neglect the anisotropic electric
      conductivity of the tissue in the forward problem. Moreover, their results are
      often confined to the heart-torso interface. We propose a forward model that
      fully accounts for the anisotropic tissue conductivity and produces the standard
      12-lead ECG in a few seconds. The activation sequence is approximated with an
      eikonal model in the 3d myocardium, while the ECG is computed with the lead-field
      approach. Both solvers were implemented on graphics processing units and
      massively parallelized. We studied the numerical convergence and scalability of
      the approach. We also compared the method to the bidomain model in terms of ECGs
      and activation maps, using a simplified but physiologically motivated geometry
      and 6 patient-specific anatomies. The proposed methods provided a good
      approximation of activation maps and ECGs computed with a bidomain model, in only
      a few seconds. Both solvers scaled very well to high-end hardware. These methods
      are suitable for use in ECG imaging methods, and may soon become fast enough for
      use in interactive simulation tools.

PMID- 28512435
TI  - The Role of Self-esteem and Fear of Negative Evaluation in Compulsive Buying.
AB  - Compulsive buying is a relatively new addictive disorder that interferes with
      everyday functioning and may result in serious psychological and financial
      problems (1). A very few data are currently available regarding this behavioral
      addiction. This study investigated gender differences in the relationships
      between contingent self-esteem (CSE), fear of negative evaluation (FNE), and
      compulsive buying. Participants included 240 Italian adults (170 females, M age =
      33.80) who responded to self-report questionnaires. The results showed that women
      scored higher on CSE and FNE scales than men. No gender differences were found in
      compulsive buying tendencies. CSE and FNE were positively related to CB.
      Furthermore, structural equation modeling confirmed the evidence on CSE as a
      strong predictor of CB for both genders. Interestingly, FNE seems to play a
      mediating role between CSE and compulsive buying behaviors only for women. These
      findings highlight the importance of studying self-esteem in compulsive buying
      tendencies to inquire more deeply into the underlying mechanisms of some
      compulsive behaviors.

PMID- 28512437
TI  - Behavioral Patterns in Special Education. Good Teaching Practices.
AB  - Providing quality education means to respond to the diversity in the classroom.
      The teacher is a key figure in responding to the various educational needs
      presented by students. Specifically, special education professionals are of great
      importance as they are the ones who lend their support to regular classroom
      teachers and offer specialized educational assistance to students who require it.
      Therefore, special education is different from what takes place in the regular
      classroom, demanding greater commitment by the teacher. There are certain
      behaviors, considered good teaching practices, which teachers have always been
      connected with to achieve good teaching and good learning. To ensure that these
      teachers are carrying out their educational work properly it is necessary to
      evaluate. This means having appropriate instruments. The Observational Protocol
      for Teaching Functions in Primary School and Special Education (PROFUNDO-EPE,
      v.3., in Spanish) allows to capture behaviors from these professionals and
      behavioral patterns that correspond to good teaching practices. This study
      evaluates the behavior of two special education teachers who work with students
      from different educational stages and educational needs. It reveals that the
      analyzed teachers adapt their behavior according the needs and characteristics of
      their students to the students responding more adequately to the needs presented
      by the students and showing good teaching practices. The patterns obtained
      indicate that they offer support, help and clear guidelines to perform the tasks.
      They motivate them toward learning by providing positive feedback and they check
      that students have properly assimilated the contents through questions or non
      verbal supervision. Also, they provide a safe and reliable climate for learning.

PMID- 28512436
TI  - Transition to Kindergarten: Negative Associations between the Emotional
      Availability in Mother-Child Relationships and Elevated Cortisol Levels in
      Children with an Immigrant Background.
AB  - Background: The transition to child care is a challenging time in a child's life
      and leads to elevated levels of cortisol. These elevations may be influenced by
      the quality of the mother-child relationship. However, remarkably little is known
      about cortisol production in response to the beginning of child care among
      children-at-risk such as children with an immigrant background. However,
      attending kindergarten or any other child day-care institution can for example
      have a compensating effect on potential language deficits thus improving the
      educational opportunities of these children. Method: Data of a subsample of N =
      24 "hard-to-reach" mother-child dyads was collected in the context of the
      psychoanalytic early prevention project FIRST STEPS. The project focuses on the
      earliest integration of children with an immigrant background by supporting
      parenting capacities in the critical phase of migration and early parenthood.
      Children's hair cortisol concentration (HCC) was assessed 1 week before (mean age
      = 38.77 months) and 3 months after kindergarten entry (mean age = 42.26 months).
      Hair analysis was conducted for both times of measurement, reflecting the first 3
      months after kindergarten entry and 3 months prior. Furthermore, the emotional
      quality of the mother-child relationship was assessed with the help of the
      Emotional Availability Scales (EAS; Biringen, 2008) shortly before kindergarten
      entry when the children were about 3 years old (mean age = 37.2). Results and
      Conclusion: Children's mean cumulated HCC was higher after kindergarten entry
      than before. The increase correlated negatively with several dimensions of the
      EAS. Repeated measures ANCOVA revealed that particularly responsive children and
      children who had experienced less intrusive mother-child relationships
      demonstrated lower elevations in HCC after kindergarten entry. Furthermore, a
      decreased EA score was found in all EA dimensions, besides the dimension
      "mother's non-hostility," indicating problematic EA within the mother-child
      relationships of the sample. The results suggest that children with an immigrant
      background who experience more emotional available mother-child relationships
      seem to regulate stress induced by kindergarten entry more effectively, indicated
      by lower cortisol elevations after entry. This implicates that supporting early
      mother-child relationships by intervention may have a positive effect on the
      children's ability to regulate stress induced by kindergarten entry thus
      promoting child development.

PMID- 28512438
TI  - Are Neurodynamic Organizations A Fundamental Property of Teamwork?
AB  - When performing a task it is important for teams to optimize their strategies and
      actions to maximize value and avoid the cost of surprise. The decisions teams
      make sometimes have unintended consequences and they must then reorganize their
      thinking, roles and/or configuration into corrective structures more appropriate
      for the situation. In this study we ask: What are the neurodynamic properties of
      these reorganizations and how do they relate to the moment-by-moment, and longer,
      performance-outcomes of teams?. We describe an information-organization approach
      for detecting and quantitating the fluctuating neurodynamic organizations in
      teams. Neurodynamic organization is the propensity of team members to enter into
      prolonged (minutes) metastable neurodynamic relationships as they encounter and
      resolve disturbances to their normal rhythms. Team neurodynamic organizations
      were detected and modeled by transforming the physical units of each team
      member's EEG power levels into Shannon entropy-derived information units about
      the team's organization and synchronization. Entropy is a measure of the
      variability or uncertainty of information in a data stream. This physical unit to
      information unit transformation bridges micro level social coordination events
      with macro level expert observations of team behavior allowing multimodal
      comparisons across the neural, cognitive and behavioral time scales of teamwork.
      The measures included the entropy of each team member's data stream, the overall
      team entropy and the mutual information between dyad pairs of the team. Mutual
      information can be thought of as periods related to team member synchrony.
      Comparisons between individual entropy and mutual information levels for the dyad
      combinations of three-person teams provided quantitative estimates of the
      proportion of a person's neurodynamic organizations that represented periods of
      synchrony with other team members, which in aggregate provided measures of the
      overall degree of neurodynamic interactions of the team. We propose that
      increased neurodynamic organization occurs when a team's operating rhythm can no
      longer support the complexity of the task and the team needs to expend energy to
      re-organize into structures that better minimize the "surprise" in the
      environment. Consistent with this hypothesis, the frequency and magnitude of
      neurodynamic organizations were less in experienced military and healthcare teams
      than they were in more junior teams. Similar dynamical properties of neurodynamic
      organization were observed in models of the EEG data streams of military,
      healthcare and high school science teams suggesting that neurodynamic
      organization may be a common property of teamwork. The innovation of this study
      is the potential it raises for developing globally applicable quantitative models
      of team dynamics that will allow comparisons to be made across teams, tasks and
      training protocols.

PMID- 28512439
TI  - Long-Time Exposure to Violent Video Games Does Not Show Desensitization on
      Empathy for Pain: An fMRI Study.
AB  - As a typical form of empathy, empathy for pain refers to the perception and
      appraisal of others' pain, as well as the corresponding affective responses.
      Numerous studies investigated the factors affecting the empathy for pain, in
      which the exposure to violent video games (VVGs) could change players' empathic
      responses to painful situations. However, it remains unclear whether exposure to
      VVG influences the empathy for pain. In the present study, in terms of the
      exposure experience to VVG, two groups of participants (18 in VVG group, VG; 17
      in non-VVG group, NG) were screened from nearly 200 video game experience
      questionnaires. And then, the functional magnetic resonance imaging data were
      recorded when they were viewing painful and non-painful stimuli. The results
      showed that the perception of others' pain were not significantly different in
      brain regions between groups, from which we could infer that the desensitization
      effect of VVGs was overrated.

PMID- 28512440
TI  - Clinical Depression and Punishment Sensitivity on the BART.
AB  - Depression is associated with altered sensitivity to reward and punishment, which
      can influence complex decision-making. We examined punishment sensitivity in the
      performance of participants with major depressive disorder (MDD) with that of a
      comparison group on the automatic Balloon Analogue Risk Task (BART), which is a
      direct measure of risk taking. The present study examined the BART performance of
      30 individuals with MDD and 30 matched comparison individuals. The comparison
      group (M = 63.25) entered a significantly (p < 0.001; d = 1.1) higher number of
      pumps on the BART than the MDD group (M = 50.83). Higher levels of depression
      symptoms were significantly correlated (r = -0.40, p < 0.05) with entering a
      lower number of pumps in the MDD group. MDD patients showed an increased
      sensitivity to punishment on the BART: after a loss, the MDD group decreased (M =
      13.7) the number of subsequent pumps they entered by a significantly (p < 0.001,
      d = 0.81) greater amount than the comparison group (M = 4.35). This difference
      applied to losses only: no difference was found between the groups regarding the
      magnitude of change in pumps selected after a win. Findings suggest the presence
      of elevated punishment sensitivity among individuals with MDD, which may
      contribute to the maintenance of depressive symptoms.

PMID- 28512441
TI  - Mapping the Paths from Styles of Anger Experience and Expression to Obsessive
      Compulsive Symptoms: The Moderating Roles of Family Cohesion and Adaptability.
AB  - Previous research has shown strong connections of anger experience and expression
      with obsessive-compulsive (OC) symptoms. Additionally, studies have demonstrated
      links between family environment variables and obsessive-compulsive disorder
      (OCD). Our study aims to integrate the perspectives from these two literatures by
      exploring the moderating roles of family cohesion and family adaptability in the
      relationship between anger proneness and suppression and OCD symptoms. A total of
      2008 college students were recruited from a comprehensive university in Shanghai,
      China between February and May 2016. The subjects completed self-report
      inventories, including the Symptom Check List-90, State-Trait Anger Expression
      Inventory 2 (Chinese version), and Family Adaptability and Cohesion Scale, second
      edition (Chinese Version). Controlling for age, one-child family status,
      ethnicity, family income, current depression, and anxiety, our analyses showed
      that the association between anger proneness and OC symptoms was moderated by
      family cohesion among men and that family adaptability moderated the connection
      between anger suppression and OC complaints among women. The findings imply that
      a more cohesive and empathic family environment may protect male students with
      high levels of anger proneness from developing OC behaviors or thoughts. The
      results suggest that for female subjects who are accustomed to suppressing angry
      feelings, flexible family coping strategies and communication atmospheres would
      reduce their vulnerability to OC symptoms. The findings are somewhat consistent
      with those of previous studies on psychotherapy outcomes that showed that OCD
      patients benefitted from psychotherapeutic interventions that cultivated the
      clients' family cohesion and adaptability.

PMID- 28512442
TI  - Posterior-Anterior Brain Maturation Reflected in Perceptual, Motor and Cognitive
      Performance.
AB  - Based on several postmortem morphometric and in vivo imaging studies it has been
      postulated that brain maturation roughly follows a caudal to rostral direction.
      In this study, we linked this maturational pattern to psychological function
      employing a series of well-established behavioral tasks. We addressed three
      distinct functions and brain regions with a perceptual (contour integration, CI),
      motor (finger tapping, FT), and executive control (Navon global-local) task. Our
      purpose was to investigate basic visual integration functions relying on primary
      visual cortex (V1) in CI; motor coordination function related to primary motor
      cortex (M1) in FT, and the executive control component, switching, related to the
      dorsolateral prefrontal region of the brain in the Navon task. 122 volunteer
      subjects were recruited to participate in this study between the ages of 10 and
      20 (females n = 63, males n = 59). Employing conventional statistical methods, we
      found that 10 and 12 year olds are performing significantly weaker than 20 year
      olds in all three tasks. In the CI and Navon global-local tasks, even 14 years
      old perform poorer than adults. We have also investigated the developmental
      trajectories by fitting sigmoid curves on our data streams. The analysis of the
      developmental trajectories of the three tasks showed a posterior to anterior
      pattern in the emergence of the developmental functions with the earliest
      development in the visual CI task (V1), followed by motor development in the FT
      task (M1), and cognitive development as measured in the Navon global-local task
      (DLPC) being the slowest. Gender difference was also present in FT task showing
      an earlier maturation for girls in the motor domain.

PMID- 28512443
TI  - Transcranial Direct Current Stimulation for Post-Concussion Syndrome: Study
      Protocol for a Randomized Crossover Trial.
AB  - BACKGROUND: Mild traumatic brain injury (MTBI) represents 70-80% of all treated
      brain injuries. A considerable proportion of MTBI patients experience post
      concussion symptoms for a prolonged period after MTBI, and these symptoms are
      diagnosed as persistent post-concussion syndrome (PPCS). PPCS is defined as a
      range of physical, cognitive, and emotional symptoms. However, memory and
      executive dysfunction seems to be one of the most debilitating symptoms.
      Recently, non-invasive brain stimulation has been studied as a potential
      treatment method for traumatic brain injury (TBI) patients. Therefore, our
      primary goal is to verify the effects of transcranial direct current stimulation
      (tDCS) in patients with PPCS who demonstrate cognitive deficits in long-term
      episodic memory, working memory, and executive function following MTBI.
      METHODS/DESIGN: This is a randomized crossover trial of patients with a history
      of MTBI with cognitive deficits in memory and executive function. Thirty adult
      patients will be randomized in a crossover manner to receive three weekly
      sessions of anodal tDCS (2 mA) at left dorsolateral prefrontal cortex, left
      temporal cortex, and sham stimulation that will be performed at 7-day intervals
      (washout period). The clinical diagnosis of PPCS will be determined using the
      Rivermead Post-Concussion Symptoms Questionnaire. Patients who meet the inclusion
      criteria will be assessed with a neuropsychological evaluation. A new battery of
      computerized neuropsychological tests will be performed before and immediately
      after each stimulation. Statistical analysis will be performed to determine
      trends of cognitive improvement. DISCUSSION: There is paucity of studies
      regarding the use of tDCS in TBI patients, and although recent results showed
      controversial data regarding the effects of tDCS in such patients, we will
      address specifically patients with PPCS and MTBI and no brain abnormalities on CT
      scan other than subarachnoid hemorrhage. Moreover, due to the missing information
      on literature regarding the best brain region to be studied, we will evaluate two
      different regions to find immediate effects of tDCS on memory and executive
      dysfunction. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier
      NCT02292589 (https://register.clinicaltrials.gov).

PMID- 28512445
TI  - The Therapeutic Value of Bone Marrow-Derived Endothelial Progenitor Cell
      Transplantation after Intracerebral Hemorrhage in Rats.
AB  - AIMS: To study the effect of endothelial progenitor cell (EPC) treatment on
      intracerebral hemorrhage (ICH) in rats and elucidate possible mechanisms.
      METHODS: The rats were randomly divided into three groups: (1) EPC group: ICH +
      EPC, (2) phosphate-buffered saline group: ICH + PBS, and (3) sham group. EPCs
      were transplanted intravenously 6 h after ICH. Modified neurological severity
      score was used to evaluate neurological function. Blood-brain barrier (BBB)
      integrity was evaluated. Dead cells, inflammatory cytokines, and neuroprotective
      cytokines were assessed to investigate possible mechanisms. RESULTS: The animals
      in the EPC group showed significant improvement in neurological function at 48 h,
      72 h, and 7 days after ICH, compared with those in the PBS group. EPC
      transplantation significantly reduced brain edema and the number of dead cells in
      the hematoma boundary areas. The intensity of Evans Blue was decreased, and
      expression levels of zonula occluden-1 and claudin-5 were increased in the EPC
      group. Proinflammatory cytokines, including interferon-gamma, IL-6, and TNF
      alpha, were decreased, whereas anti-inflammatory cytokines, including
      transforming growth factor-beta1 and IL-10, were increased in the EPC group. In
      addition, expression levels of brain-derived neurotrophic factor, vascular
      endothelial growth factor, and neurotrophic growth factor were increased
      following transplantation of EPCs. CONCLUSION: EPC transplantation could improve
      neurological function of ICH rats. The protective effect may be mediated by
      promotion of neuroprotective cytokine secretion, restoration of the BBB,
      reduction of cell death, and the decrease in inflammation.

PMID- 28512444
TI  - Longitudinal Quantification of Eye-Movement Impairments after Pontine Hemorrhage.
AB  - INTRODUCTION: We report a case of hypertrophic olivary degeneration due to
      pontine hemorrhage. A 59-year-old male with untreated hypertension suffered a
      primary pontine hemorrhage, which caused horizontal eye-movement limitation.
      Progressive neurological deterioration with involuntary eye and palatal movements
      began months after hemorrhage. This was accompanied by magnetic resonance imaging
      evidence of hypertrophic olivary degeneration at 4.5 months. BACKGROUND: Primary
      pontine hemorrhage often leads to impairment of eye movements and diplopia.
      Hypertrophic olivary degeneration can also emerge months after hemorrhage,
      producing involuntary pendular eye movements. Neither the natural history of
      voluntary eye movements nor the emergence of involuntary eye movements after
      pontine hemorrhage has been previously quantified. METHODS: We used an
      optokinetic task that enabled measurement of eye movements. It provided real-time
      feedback on the ability to track continuously and saccade quickly in a pursuit
      task. The feedback motivated the patient to use the system repeatedly in his
      home. From 3 months after hemorrhage, the patient used the system for 9 months,
      allowing us to quantify changes in his eye movements. RESULTS: Horizontal gaze
      impairments were manifest in our task as limitation in horizontal range of
      motion, as well as delay in initiation of the right eye's movement during left-to
      right pursuit. Improvement in these impairments was measured over the course of
      months 3-7 post hemorrhage. In addition, the emergence of vertical pendular
      nystagmus was identified in the subject at 4 months. Analysis of the eye-movement
      records revealed presymptomatic oscillatory eye movements whose amplitude had
      grown steadily over the course of 3 weeks, prior to a sharp increase in amplitude
      that coincided with the patient's first report of oscillopsia. Horizontal
      pendular nystagmus emerged 7.4 months after the hemorrhage, primarily in the left
      eye. CONCLUSION: An eye-tracking system deployed in a patient's home enabled
      prospective longitudinal quantification of the natural history and improvement in
      voluntary eye-movement impairments after pontine hemorrhage. It also
      characterized prospectively for the first time, the emergence of involuntary eye
      movements resulting from the rare complication of hypertrophic olivary
      degeneration. Results suggest that brief weekly measurements with an eye-tracker
      may allow early detection of this complication.

PMID- 28512446
TI  - Neuroprotective Roles of l-Cysteine in Attenuating Early Brain Injury and
      Improving Synaptic Density via the CBS/H2S Pathway Following Subarachnoid
      Hemorrhage in Rats.
AB  - l-Cysteine is a semi-essential amino acid and substrate for cystathionine-beta
      synthase (CBS) in the central nervous system. We previously reported that NaHS,
      an H2S donor, significantly alleviated brain damage after subarachnoid hemorrhage
      (SAH) in rats. However, the potential therapeutic value of l-cysteine and the
      molecular mechanism supporting these beneficial effects have not been determined.
      This study was designed to investigate whether l-cysteine could attenuate early
      brain injury following SAH and improve synaptic function by releasing endogenous
      H2S. Male Wistar rats were subjected to SAH induced by cisterna magna blood
      injection, and l-cysteine was intracerebroventricularly administered 30 min after
      SAH induction. Treatment with l-cysteine stimulated CBS activity in the
      prefrontal cortex (PFC) and H2S production. Moreover, l-cysteine treatment
      significantly ameliorated brain edema, improved neurobehavioral function, and
      attenuated neuronal cell death in the PFC; these effects were associated with a
      decrease in the Bax/Bcl-2 ratio and the suppression of caspase-3 activation 48 h
      after SAH. Furthermore, l-cysteine treatment activated the CREB-brain-derived
      neurotrophic factor (BDNF) pathway and intensified synaptic density by regulating
      synapse proteins 48 h after SAH. Importantly, all the beneficial effects of l
      cysteine in SAH were abrogated by amino-oxyacetic acid, a CBS inhibitor. Based on
      these findings, l-cysteine may play a neuroprotective role in SAH by inhibiting
      cell apoptosis, upregulating CREB-BDNF expression, and promoting synaptic
      structure via the CBS/H2S pathway.

PMID- 28512448
TI  - The Potential Role of Contraction-Induced Myokines in the Regulation of Metabolic
      Function for the Prevention and Treatment of Type 2 Diabetes.
AB  - Skeletal muscle represents the largest organ in the body, comprises 36-42% of
      body weight, and has recently been recognized as having an endocrine function.
      Proteins expressed and released by muscle that have autocrine, paracrine, and
      endocrine bioactivities have been termed myokines. It is likely that muscle
      contraction represents the primary stimulus for the synthesis and secretion of
      myokines to enable communication with other organs such as the liver, adipose
      tissue, brain, and auto-regulation of muscle metabolism. To date, several hundred
      myokines in the muscle secretome have been identified, a sub-population of which
      are specifically induced by skeletal muscle contraction. However, the bioactivity
      of many of these myokines and the mechanism through which they act has either not
      yet been characterized or remains poorly understood. Physical activity and
      exercise are recognized as a central tenet in both the prevention and treatment
      of type 2 diabetes (T2D). Recent data suggest humoral factors such as muscle
      derived secretory proteins may mediate the beneficial effects of exercise in the
      treatment of metabolic diseases. This mini-review aims to summarize our current
      knowledge on the role of contraction-induced myokines in mediating the beneficial
      effects of physical activity and exercise in the prevention and treatment of T2D,
      specifically glucose and lipid metabolism. Future directions as to how we can
      optimize contraction-induced myokine secretion to inform exercise protocols for
      the prevention and treatment of T2D will also be discussed.

PMID- 28512447
TI  - Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral
      Neuropathy.
AB  - Diabetic peripheral neuropathy (DPN) remains one of the most common and serious
      complications of diabetes. Currently, pharmacological agents are limited to
      treating the pain associated with DPN, and do not address the underlying
      pathological mechanisms driving nerve damage, thus leaving a significant unmet
      medical need. Interestingly, research conducted using exercise as a treatment for
      DPN has revealed interleukin-6 (IL-6) signaling to be associated with many
      positive benefits such as enhanced blood flow and lipid metabolism, decreased
      chronic inflammation, and peripheral nerve fiber regeneration. IL-6, once known
      solely as a pro-inflammatory cytokine, is now understood to signal as a
      multifunctional cytokine, capable of eliciting both pro- and anti-inflammatory
      responses in a context-dependent fashion. IL-6 released from muscle in response
      to exercise signals as a myokine and as such has a unique kinetic profile,
      whereby levels are transiently elevated up to 100-fold and return to baseline
      levels within 4 h. Importantly, this kinetic profile is in stark contrast to long
      term IL-6 elevation that is associated with pro-inflammatory states. Given
      exercise induces IL-6 myokine signaling, and exercise has been shown to elicit
      numerous beneficial effects for the treatment of DPN, a causal link has been
      suggested. Here, we discuss both the clinical and preclinical literature related
      to the application of IL-6 as a treatment strategy for DPN. In addition, we
      discuss how IL-6 may directly modulate Schwann and nerve cells to explore a
      mechanistic understanding of how this treatment elicits a neuroprotective and/or
      regenerative response. Collectively, studies suggest that IL-6, when administered
      in a low-dose pulsatile strategy to mimic the body's natural response to
      exercise, may prove to be an effective treatment for the protection and/or
      restoration of peripheral nerve function in DPN. This review highlights the
      studies supporting this assertion and provides rationale for continued
      investigation of IL-6 for the treatment of DPN.

PMID- 28512449
TI  - Antibacterial Potential of an Antimicrobial Agent Inspired by Peroxidase
      Catalyzed Systems.
AB  - Antibiotic resistance is an increasingly serious threat to global health.
      Consequently, the development of non-antibiotic based therapies and
      disinfectants, which avoid induction of resistance, or cross-resistance, is of
      high priority. We report the synthesis of a biocidal complex, which is produced
      by the reaction between ionic oxidizable salts-iodide and thiocyanate-in the
      presence of hydrogen peroxide as an oxidation source. The reaction generates
      bactericidal reactive oxygen and iodine species. In this study, we report that
      the iodo-thiocyanate complex (ITC) is an effective bactericidal agent with
      activity against planktonic and biofilm cells of Gram-negative (Escherichia coli
      and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and
      methicillin-resistant S. aureus) bacteria. The minimum bactericidal
      concentrations and the minimum biofilm eradication concentrations of the biocidal
      composite were in the range of 7.8-31.3 and 31.3-250 MUg ml-1, respectively. As a
      result, the complex was capable to cause a rapid cell death of planktonic test
      cultures at between 0.5 and 2 h, and complete eradication of dual and mono
      species biofilms between 30 s and 10 min. Furthermore, the test bacteria,
      including a MRSA strain, exposed to the cocktail failed to develop resistance
      after serial passages. The antimicrobial activity of the ITC appears to derive
      from the combinational effect of the powerful species capable of oxidizing the
      essential biomolecules of bacteria. The use of this composition may provide an
      effective and efficient method for killing potential pathogens, as well as for
      disinfecting and removing biofilm contamination.

PMID- 28512450
TI  - Host Plant Compatibility Shapes the Proteogenome of Frankia coriariae.
AB  - Molecular signaling networks in the actinorhizal rhizosphere select host
      compatible Frankia strains, trigger the infection process and eventually the
      genesis of nitrogen-fixing nodules. The molecular triggers involved remain
      difficult to ascertain. Root exudates (RE) are highly dynamic substrates that
      play key roles in establishing the rhizosphere microbiome. RE are known to induce
      the secretion by rhizobia of Nod factors, polysaccharides, and other proteins in
      the case of legume symbiosis. Next-generation proteomic approach was here used to
      decipher the key bacterial signals matching the first-step recognition of host
      plant stimuli upon treatment of Frankia coriariae strain BMG5.1 with RE derived
      from compatible (Coriaria myrtifolia), incompatible (Alnus glutinosa), and non
      actinorhizal (Cucumis melo) host plants. The Frankia proteome dynamics were
      mainly driven by host compatibility. Both metabolism and signal transduction were
      the dominant activities for BMG5.1 under the different RE conditions tested. A
      second set of proteins that were solely induced by C. myrtifolia RE and were
      mainly linked to cell wall remodeling, signal transduction and host signal
      processing activities. These proteins may footprint early steps in receptive
      recognition of host stimuli before subsequent events of symbiotic recruitment.

PMID- 28512452
TI  - Towards Identifying Protective B-Cell Epitopes: The PspA Story.
AB  - Pneumococcal surface protein A (PspA) is one of the most abundant cell surface
      protein of Streptococcus pneumoniae (S. pneumoniae). PspA variants are
      structurally and serologically diverse and help evade complement-mediated
      phagocytosis of S. pneumoniae, which is essential for its survival in the host.
      PspA is currently been screened for employment in the generation of more
      effective (serotype independent) vaccine to overcome the limitations of
      polysaccharide based vaccines, providing serotype specific immune responses. The
      cross-protection eliciting regions of PspA localize to the alpha-helical and
      proline rich regions. Recent data indicate significant variation in the ability
      of antibodies induced against the recombinant PspA variants to recognize distinct
      S. pneumoniae strains. Hence, screening for the identification of the
      topographical repertoire of B-cell epitopes that elicit cross-protective immune
      response seems essential in the engineering of a superior PspA-based vaccine.
      Herein, we revisit epitope identification in PspA and the utility of hybridoma
      technology in directing the identification of protective epitope regions of PspA
      that can be used in vaccine research.

PMID- 28512453
TI  - Alterations in the Rumen Liquid-, Particle- and Epithelium-Associated Microbiota
      of Dairy Cows during the Transition from a Silage- and Concentrate-Based Ration
      to Pasture in Spring.
AB  - In spring dairy cows are often gradually transitioned from a silage- and
      concentrate-based ration (total mixed ration, TMR) to pasture. Rumen microbiota
      adaptability is a key feature of ruminant survival strategy. However, only little
      is known on the temporal and spatial microbial alterations involved. This study
      aims to investigate how the rumen liquid (LAAB), particle (PAAB), and epithelium
      (EAAB) associated archaea and bacteria are influenced by this nutritional change.
      A 10-wk trial was performed, including 10 rumen-fistulated dairy cows, equally
      divided into a pasture- and a confinement- group (PG and CG). The CG stayed on a
      TMR-based ration, while the PG was gradually transitioned from TMR to pasture (wk
      1: TMR-only, wk 2: 3 h/day on pasture, wk 3 & 4: 12 h/day on pasture, wk 5-10:
      pasture-only). In wk 1, wk 5, and wk 10 samples of solid and liquid rumen
      contents, and papillae biopsies were collected. The DNA was isolated, and PCR
      SSCP and 16S rRNA gene amplicon sequencing analysis were performed. Cluster
      analysis revealed a higher similarity between LAAB and PAAB, compared to the
      EAAB, characterized by higher species diversity. At all three locations the
      microbiota was significantly influenced by the ration change, opposite the
      generally acknowledged hypothesis that the EAAB remain more consistent throughout
      dietary changes. Even though the animals in the PG were already on a full-grazing
      ration for 4-6 days in wk 5, the microbiota at all three locations was
      significantly different compared to wk 10, suggesting an adaptation period of
      several days to weeks. This is in line with observations made on animal level,
      showing a required time for adaptation of 2-3 weeks for production and metabolic
      variables. A large part of the rumen prokaryote species remained unaltered upon
      transition to pasture and exhibited a strong host influence, supporting the
      hypothesis that the rumen microbiota consists of a core and a variable
      microbiota. For the effect of the location as well as the ration change either
      very similar or opposite trends among member species of common taxa were
      observed, demonstrating that microbes that are phylogenetically close may still
      exhibit substantially different phenotypes and functions.

PMID- 28512451
TI  - Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria,
      and Microeukaryotes during the First Year of Life.
AB  - Perturbations to the colonization process of the human gastrointestinal tract
      have been suggested to result in adverse health effects later in life. Although
      much research has been performed on bacterial colonization and succession, much
      less is known about the other two domains of life, archaea, and eukaryotes. Here
      we describe colonization and succession by bacteria, archaea and microeukaryotes
      during the first year of life (samples collected around days 1, 3, 5, 28, 150,
      and 365) within the gastrointestinal tract of infants delivered either vaginally
      or by cesarean section and using a combination of quantitative real-time PCR as
      well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms
      belonging to all three domains of life were detectable in all of the collected
      meconium samples. The microeukaryotic community composition fluctuated strongly
      over time and early diversification was delayed in infants receiving formula
      milk. Cesarean section-delivered (CSD) infants experienced a delay in
      colonization and succession, which was observed for all three domains of life.
      Shifts in prokaryotic succession in CSD infants compared to vaginally delivered
      (VD) infants were apparent as early as days 3 and 5, which were characterized by
      increased relative abundances of the genera Streptococcus and Staphylococcus, and
      a decrease in relative abundance for the genera Bifidobacterium and Bacteroides.
      Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum
      in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio
      between days 5 and 150 when compared to VD infants. Although the delivery mode
      appeared to have the strongest influence on differences between the infants,
      other factors such as a younger gestational age or maternal antibiotics intake
      likely contributed to the observed patterns as well. Our findings complement
      previous observations of a delay in colonization and succession of CSD infants,
      which affects not only bacteria but also archaea and microeukaryotes. This
      further highlights the need for resolving bacterial, archaeal, and
      microeukaryotic dynamics in future longitudinal studies of microbial colonization
      and succession within the neonatal gastrointestinal tract.

PMID- 28512454
TI  - New Insights into the Regulation of Cell-Surface Signaling Activity Acquired from
      a Mutagenesis Screen of the Pseudomonas putida IutY Sigma/Anti-Sigma Factor.
AB  - Cell-surface signaling (CSS) is a signal transfer system that allows Gram
      negative bacteria to detect environmental signals and generate a cytosolic
      response. These systems are composed of an outer membrane receptor that senses
      the inducing signal, an extracytoplasmic function sigma factor (sigmaECF) that
      targets the cytosolic response by modifying gene expression and a cytoplasmic
      membrane anti-sigma factor that keeps the sigmaECF in an inactive state in the
      absence of the signal and transduces its presence from the outer membrane to the
      cytosol. Although CSS systems regulate bacterial processes as crucial as stress
      response, iron scavenging and virulence, the exact mechanisms that drive CSS are
      still not completely understood. Binding of the signal to the CSS receptor is
      known to trigger a signaling cascade that results in the regulated proteolysis of
      the anti-sigma factor and the activation of the sigmaECF in the cytosol. This
      study was carried out to generate new insights in the proteolytic activation of
      CSS sigmaECF. We performed a random mutagenesis screen of the unique IutY protein
      of Pseudomonas putida, a protein that combines a cytosolic sigmaECF domain and a
      periplasmic anti-sigma factor domain in a single polypeptide. In response to the
      presence of an iron carrier, the siderophore aerobactin, in the extracellular
      medium, IutY is processed by two different proteases, Prc and RseP, which results
      in the release and activation of the sigmaIutY domain. Our experiments show that
      all IutY mutant proteins that contain periplasmic residues depend on RseP for
      activation. In contrast, Prc is only required for mutant variants with a
      periplasmic domain longer than 50 amino acids, which indicates that the
      periplasmic region of IutY is trimmed down to ~50 amino acids creating the RseP
      substrate. Moreover, we have identified several conserved residues in the CSS
      anti-sigma factor family of which mutation leads to constitutive activation of
      their cognate sigmaECF. These findings advance our knowledge on how CSS activity
      is regulated by the consecutive action of two proteases. Elucidation of the exact
      mechanism behind CSS activation will enable the development of strategies to
      block CSS in pathogenic bacteria.

PMID- 28512455
TI  - Non-edible Oil Cakes as a Novel Substrate for DPA Production and Augmenting
      Biocontrol Activity of Paecilomyces variotii.
AB  - The present study investigated the use of waste non-edible oil cakes (Jatropha,
      Karanja, Neem, and Mahua) as a substrate for the growth of Paecilomyces variotii
      and dipicolinic acid (DPA) production. Previous researches proved the efficacy of
      DPA in suppressing certain pathogens that are deleterious to the plants in the
      rhizosphere. DPA production was statistical optimized by amending non-edible oil
      cakes in growing media as nitrogen and sugars (Dextrose, Glucose, and Lactose) as
      carbon source. Plackett-Burman design (PBD), indicated that Jatropha cake,
      Karanja cake, and Dextrose were the most significant components (p < 0.05) of the
      media and were further optimized using response surface methodology (RSM).
      Jatropha cake, Karanja cake, and Dextrose at the concentration of 12.5, 4.5, and
      10 g/l, respectively, yielded 250 mg/l of DPA, which was 2.5 fold more than that
      obtained from basal medium. HPLC analysis of the optimized medium (peak at
      retention time of 30 min) confirmed the enhanced DPA production by P. variotii.
      The scanning electron microscopy (SEM) images showed that optimized medium impose
      a stress like condition (due to less C:N ratio) for the fungus and generated more
      spores as compared to the basal medium in which carbon source is easily available
      for the mycelial growth. The antimicrobial activity of the fungal extract was
      tested and found to be effective even at 10-2 dilution after 72 h against two
      plant pathogens, Fusarium oxysporum and Verticillium dahlia. Statistical
      experimental design of this study and the use of non-edible oil cakes as a
      substrate offer an efficient and viable approach for DPA production by P.
      variotii.

PMID- 28512456
TI  - Proline-Based Cyclic Dipeptides from Korean Fermented Vegetable Kimchi and from
      Leuconostoc mesenteroides LBP-K06 Have Activities against Multidrug-Resistant
      Bacteria.
AB  - Lactobacillus plantarum and Leuconostoc mesenteroides play a prominent role as
      functional starters and predominant isolates in the production of various types
      of antimicrobial compound-containing fermented foods, especially including
      kimchi. In the case of the bioactive cyclic dipeptides, their racemic
      diastereomers inhibitory to bacteria and fungi have been suggested to come solely
      from Lactobacillus spp. of these strains. We previously demonstrated the
      antifungal and antiviral activities of proline-based cyclic dipeptides, which
      were fractionated from culture filtrates of Lb. plantarum LBP-K10 originated from
      kimchi. However, cyclic dipeptides have not been identified in the filtrates,
      either from cultures or fermented subject matter, driven by Ln. mesenteroides,
      which have been widely used as starter cultures for kimchi fermentation. Most
      importantly, the experimental verification of cyclic dipeptide-content changes
      during kimchi fermentation have also not been elucidated. Herein, the
      antibacterial fractions, including cyclo(Leu-Pro) and cyclo(Phe-Pro), from Ln.
      mesenteroides LBP-K06 culture filtrates, which exhibited a typical
      chromatographic retention behavior (tR), were identified by using semi
      preparative high-performance liquid chromatography and gas chromatography-mass
      spectrometry. Based on this finding, the proline-based cyclic dipeptides,
      including cyclo(Ser-Pro), cyclo(Tyr-Pro), and cyclo(Leu-Pro), were additionally
      identified in the filtrates only when fermenting Chinese cabbage produced with
      Ln. mesenteroides LBP-K06 starter cultures. The detection and isolation of cyclic
      dipeptides solely in controlled fermented cabbage were conducted under the
      control of fermentation-process parameters concomitantly with strong CDP
      selectivity by using a two-consecutive-purification strategy. Interestingly,
      cyclic dipeptides in the filtrates, when using this strain as a starter,
      increased with fermentation time. However, no cyclic dipeptides were observed in
      the filtrates of other fermented products, including other types of kimchi and
      fermented materials of plant and animal origin. This is the first report to
      conclusively demonstrate evidence for the existence of antimicrobial cyclic
      dipeptides produced by Ln. mesenteroides in kimchi. Through filtrates from lactic
      acid bacterial cultures and from fermented foods, we have also proved a method of
      combining chromatographic fractionation and mass spectrometry-based analysis for
      screening cyclic dipeptide profiling, which may allow evaluation of the fermented
      dairy foods from a new perspective.

PMID- 28512457
TI  - The 25-26 nt Small RNAs in Phytophthora parasitica Are Associated with Efficient
      Silencing of Homologous Endogenous Genes.
AB  - Small RNAs (sRNAs) are important non-coding RNA regulators, playing key roles in
      developmental regulation, transposon suppression, environmental response, host
      pathogen interaction and other diverse biological processes. However, their roles
      in oomycetes are poorly understood. Here, we performed sRNA sequencing and RNA
      sequencing of Phytophthora parasitica at stages of vegetative growth and
      infection of Arabidopsis roots to examine diversity and function of sRNAs in P.
      parasitica, a model hemibiotrophic oomycete plant pathogen. Our results indicate
      that there are two distinct types of sRNA-generating loci in P. parasitica
      genome, giving rise to clusters of 25-26 nt and 21 nt sRNAs, respectively, with
      no significant strand-biases. The 25-26 nt sRNA loci lie predominantly in gene
      sparse and repeat-rich regions, and overlap with over 7000 endogenous gene loci.
      These overlapped genes are typically P. parasitica species-specific, with no
      homologies to the sister species P. infestans. They include approximately 40%
      RXLR effector genes, 50% CRN effector genes and some elicitor genes. The
      transcripts of most of these genes could not be detected at both the vegetative
      mycelium and infection stages as revealed by RNA sequencing, indicating that the
      25-26 nt sRNAs are associated with efficient silencing of these genes. The 21 nt
      sRNA loci typically overlap with the exon regions of highly expressed genes,
      suggesting that the biogenesis of the 21 nt sRNAs may be dependent on the level
      of gene transcription and that these sRNAs do not mediate efficient silencing of
      homologous genes. Analyses of the published P. infestans sRNA and mRNA sequencing
      data consistently show that the 25-26 nt sRNAs, but not the 21 nt sRNAs, may
      mediate efficient gene silencing in Phytophthora.

PMID- 28512458
TI  - A Mitochondrial Autonomously Replicating Sequence from Pichia pastoris for
      Uniform High Level Recombinant Protein Production.
AB  - Pichia pastoris is a non-conventional methylotrophic yeast that is widely used
      for recombinant protein production, typically by stably integrating the target
      gene into the genome as part of an expression cassette. However, the
      comparatively high clonal variability associated with this approach usually
      necessitates a time intense screening step in order to find strains with the
      desired productivity. Some of the factors causing this clonal variability can be
      overcome using episomal vectors containing an autonomously replicating sequence
      (ARS). Here, we report on the discovery, characterization, and application of a
      fragment of mitochondrial DNA from P. pastoris for use as an ARS. First
      encountered as an off-target event in an experiment aiming for genomic
      integration, the newly created circular plasmid named "pMito" consists of the
      expression cassette and a fragment of mitochondrial DNA. Multiple matches to
      known ARS consensus sequence motifs, but no exact match to known chromosomal ARS
      from P. pastoris were detected on the fragment, indicating the presence of a
      novel ARS element. Different variants of pMito were successfully used for
      transformation and their productivity characteristics were assayed. All analyzed
      clones displayed a highly uniform expression level, exceeding by up to fourfold
      that of a reference with a single copy integrated in its genome. Expressed GFP
      could be localized exclusively to the cytoplasm via super-resolution fluorescence
      microscopy, indicating that pMito is present in the nucleus. While expression
      levels were homogenous among pMito clones, an apparent upper limit of expression
      was visible that could not be explained based on the gene dosage. Further
      investigation is necessary to fully understand the bottle-neck hindering this and
      other ARS vectors in P. pastoris from reaching their full capability. Lastly, we
      could demonstrate that the mitochondrial ARS from P. pastoris is also suitable
      for episomal vector transformation in Saccharomyces cerevisiae, widening the
      potential for biotechnological application. pMito displayed strong potential to
      reduce clonal variability in experiments targeting recombinant protein
      production. These findings also showcase the as of yet largely untapped potential
      of mitochondrial ARS from different yeasts for biotechnological applications.

PMID- 28512459
TI  - In Vivo Chronic Stimulation Unveils Autoreactive Potential of Wiskott-Aldrich
      Syndrome Protein-Deficient B Cells.
AB  - Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency caused by mutations
      in the gene encoding the hematopoietic-specific WAS protein (WASp). WAS is
      frequently associated with autoimmunity, indicating a critical role of WASp in
      maintenance of tolerance. The role of B cells in the induction of autoreactive
      immune responses in WAS has been investigated in several settings, but the
      mechanisms leading to the development of autoimmune manifestations have been
      difficult to evaluate in the mouse models of the disease that do not
      spontaneously develop autoimmunity. We performed an extensive characterization of
      Was-/- mice that provided evidence of the potential alteration in B cell
      selection, because of the presence of autoantibodies against double-stranded DNA,
      platelets, and tissue antigens. To uncover the mechanisms leading to the
      activation of the potentially autoreactive B cells in Was-/- mice, we performed
      in vivo chronic stimulations with toll-like receptors agonists (LPS and CpG) and
      apoptotic cells or infection with lymphocytic choriomeningitis virus. All
      treatments led to increased production of autoantibodies, increased proteinuria,
      and kidney tissue damage in Was-/- mice. These findings demonstrate that a lower
      clearance of pathogens and/or self-antigens and the resulting chronic
      inflammatory state could cause B cell tolerance breakdown leading to autoimmunity
      in WAS.

PMID- 28512460
TI  - Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment
      Strategies, and Future Prospects.
AB  - Delivery of high doses of radiation to thoracic region, particularly with non
      small cell lung cancer patients, becomes difficult due to subsequent
      complications arising in the lungs of the patient. Radiation-induced pneumonitis
      is an early event evident in most radiation exposed patients observed within 2-4
      months of treatment and leading to fibrosis later. Several cytokines and
      inflammatory molecules interplay in the vicinity of the tissue developing
      radiation injury leading to pneumonitis and fibrosis. While certain cytokines may
      be exploited as biomarkers, they also appear to be a potent target of
      intervention at transcriptional level. Initiation and progression of pneumonitis
      and fibrosis thus are dynamic processes arising after few months to year after
      irradiation of the lung tissue. Currently, available treatment strategies are
      challenged by the major dose limiting complications that curtails success of the
      treatment as well as well being of the patient's future life. Several approaches
      have been in practice while many other are still being explored to overcome such
      complications. The current review gives a brief account of the immunological
      aspects, existing management practices, and suggests possible futuristic
      approaches.

PMID- 28512463
TI  - Allometric Models for Predicting Aboveground Biomass and Carbon Stock of Tropical
      Perennial C4 Grasses in Hawaii.
AB  - Biomass is a promising renewable energy option that provides a more
      environmentally sustainable alternative to fossil resources by reducing the net
      flux of greenhouse gasses to the atmosphere. Yet, allometric models that allow
      the prediction of aboveground biomass (AGB), biomass carbon (C) stock non
      destructively have not yet been developed for tropical perennial C4 grasses
      currently under consideration as potential bioenergy feedstock in Hawaii and
      other subtropical and tropical locations. The objectives of this study were to
      develop optimal allometric relationships and site-specific models to predict AGB,
      biomass C stock of napiergrass, energycane, and sugarcane under cultivation
      practices for renewable energy and validate these site-specific models against
      independent data sets generated from sites with widely different environments.
      Several allometric models were developed for each species from data at a low
      elevation field on the island of Maui, Hawaii. A simple power model with stalk
      diameter (D) was best related to AGB and biomass C stock for napiergrass,
      energycane, and sugarcane, (R2 = 0.98, 0.96, and 0.97, respectively). The models
      were then tested against data collected from independent fields across an
      environmental gradient. For all crops, the models over-predicted AGB in plants
      with lower stalk D, but AGB was under-predicted in plants with higher stalk D.
      The models using stalk D were better for biomass prediction compared to dewlap H
      (Height from the base cut to most recently exposed leaf dewlap) models, which
      showed weak validation performance. Although stalk D model performed better,
      however, the mean square error (MSE)-systematic was ranged from 23 to 43 % of MSE
      for all crops. A strong relationship between model coefficient and rainfall was
      existed, although these were irrigated systems; suggesting a simple site-specific
      coefficient modulator for rainfall to reduce systematic errors in water-limited
      areas. These allometric equations provide a tool for farmers in the tropics to
      estimate perennial C4 grass biomass and C stock during decision-making for land
      management and as an environmental sustainability indicator within a renewable
      energy system.

PMID- 28512461
TI  - Transcriptional Responses to Pre-flowering Leaf Defoliation in Grapevine Berry
      from Different Growing Sites, Years, and Genotypes.
AB  - Leaf removal is a grapevine canopy management technique widely used to modify the
      source-sink balance and/or microclimate around berry clusters to optimize fruit
      composition. In general, the removal of basal leaves before flowering reduces
      fruit set, hence achieving looser clusters, and improves grape composition since
      yield is generally curtailed more than proportionally to leaf area itself. Albeit
      responses to this practice seem quite consistent, overall vine performance is
      affected by genotype, environmental conditions, and severity of treatment. The
      physiological responses of grape varieties to defoliation practices have been
      widely investigated, and just recently a whole genome transcriptomic approach was
      exploited showing an extensive transcriptome rearrangement in berries defoliated
      before flowering. Nevertheless, the extent to which these transcriptomic
      reactions could be manifested by different genotypes and growing environments is
      entirely unexplored. To highlight general responses to defoliation vs. different
      locations, we analyzed the transcriptome of cv. Sangiovese berries sampled at
      four development stages from pre-flowering defoliated vines in two different
      geographical areas of Italy. We obtained and validated five markers of the early
      defoliation treatment in Sangiovese, an ATP-binding cassette transporter, an
      auxin response factor, a cinnamyl alcohol dehydrogenase, a flavonoid 3-O
      glucosyltransferase and an indole-3-acetate beta-glucosyltransferase. Candidate
      molecular markers were also obtained in another three grapevine genotypes (Nero
      d'Avola, Ortrugo, and Ciliegiolo), subjected to the same level of selective pre
      flowering defoliation (PFD) over two consecutive years in their different areas
      of cultivation. The flavonol synthase was identified as a marker in the pre
      veraison phase, the jasmonate methyltransferase during the transition phase and
      the abscisic acid receptor PYL4 in the ripening phase. The characterization of
      transcriptome changes in Sangiovese berry after PFD highlights, on one hand, the
      stronger effect of environment than treatment on the whole berry transcriptome
      rearrangement during development and, on the other, expands existing knowledge of
      the main molecular and biochemical modifications occurring in defoliated vines.
      Moreover, the identification of candidate genes associated with PFD in different
      genotypes and environments provides new insights into the applicability and
      repeatability of this crop practice, as well as its possible agricultural and
      qualitative outcomes across genetic and environmental variability.

PMID- 28512464
TI  - Insights into the Mechanism of Proliferation on the Special Microbes Mediated by
      Phenolic Acids in the Radix pseudostellariae Rhizosphere under Continuous
      Monoculture Regimes.
AB  - As potent allelochemicals, phenolic acids are believed to be associated with
      replanting disease and cause microflora shift and structural disorder in the
      rhizosphere soil of continuously monocultured Radix pseudostellariae. The
      transcriptome sequencing was used to reveal the mechanisms underlying the
      differential response of pathogenic bacterium Kosakonia sacchari and beneficial
      bacterium Bacillus pumilus on their interactions with phenolic acids, the main
      allelochemicals in root exudates of R. pseudostellariae in the monoculture
      system. The microbes were inoculated in the pots containing soil and the
      medicinal plant in this study. The results showed that the addition of beneficial
      B. pumilus to the 2-year planted soil significantly decreased the activity of
      soil urease, catalase, sucrase, and cellulase and increased the activity of
      chitinase compared with those in the 2nd-year monocropping rhizosphere soil
      without any treatment. However, opposite results were obtained when K. sacchari
      was added. Transcriptome analysis showed that vanillin enhanced
      glycolysis/gluconeogenesis, fatty acid biosynthesis, pentose phosphate, bacterial
      chemotaxis, flagellar assembly, and phosphotransferase system pathway in K.
      sacchari. However, protocatechuic acid, a metabolite produced by K. sacchari from
      vanillin, had negative effects on the citrate cycle and biosynthesis of
      novobiocin, phenylalanine, tyrosine, and tryptophan in B. pumilus. Concurrently,
      the protocatechuic acid decreased the biofilm formation of B. pumilus. These
      results unveiled the mechanisms how phenolic acids differentially mediate the
      shifts of microbial flora in rhizosphere soil, leading to the proliferation of
      pathogenic bacteria (i.e., K. sacchari) and the attenuation of beneficial
      bacteria (i.e., B. pumilus) under the monocropping system of R. pseudostellariae.

PMID- 28512465
TI  - Growth, Water Use, and Nitrate-15N Uptake of Greenhouse Tomato as Influenced by
      Different Irrigation Patterns, 15N Labeled Depths, and Transplant Times.
AB  - Increasing water use efficiency and reducing nitrogen pollutant discharge are
      important tasks for modern agriculture. To evaluate the effect of alternate
      partial root-zone irrigation (APRI) on tomato plant growth, water use efficiency
      and nitrate-15N uptake, an experiment was conducted from June to December in 2014
      under greenhouse condition in northern China. The experiment contained two
      irrigation patterns [APRI and conventional irrigation (CI)], two 15N labeled
      depths in soil (10 and 50 cm) and two transplant time (early and late summer).
      Results showed that, compared to CI, APRI did not significantly (p > 0.05) impact
      the growth and biomass accumulation in aboveground part of tomato, while it
      enhanced the root, reflecting by greater length density, and more dry mass. APRI
      produced marginally lower yields, but saved 34.9% of irrigation water, and gave a
      37.6-49.9% higher water use efficiency relative to CI. In addition, APRI improved
      fruit quality, mainly through increasing the contents of soluble solid (by 12.8
      21.6%), and vitamin C (2.8-12.7%), and the sugar/acid ratio (3.5-8.5%). The 15N
      utilization efficiency (15NUE) in APRI was higher than that in CI, which was more
      evident when 15N was labeled at 50 cm depth. Significant (p < 0.05) 15N recovery
      increase of 10.2-13.2% and 15N loss decrease of 35.4-54.6% were found for APRI
      compared to CI. The overall results suggest that APRI under greenhouse could
      benefit the nitrate-N recovery and increase the water use efficiency in tomato.

PMID- 28512462
TI  - De novo Transcriptome Profiling of Flowers, Flower Pedicels and Pods of Lupinus
      luteus (Yellow Lupine) Reveals Complex Expression Changes during Organ
      Abscission.
AB  - Yellow lupine (Lupinus luteus L., Taper c.), a member of the legume family
      (Fabaceae L.), has an enormous practical importance. Its excessive flower and pod
      abscission represents an economic drawback, as proper flower and seed formation
      and development is crucial for the plant's productivity. Generative organ
      detachment takes place at the basis of the pedicels, within a specialized group
      of cells collectively known as the abscission zone (AZ). During plant growth
      these cells become competent to respond to specific signals that trigger
      separation and lead to the abolition of cell wall adhesion. Little is known about
      the molecular network controlling the yellow lupine organ abscission. The aim of
      our study was to establish the divergences and similarities in transcriptional
      networks in the pods, flowers and flower pedicels abscised or maintained on the
      plant, and to identify genes playing key roles in generative organ abscission in
      yellow lupine. Based on de novo transcriptome assembly, we identified 166,473
      unigenes representing 219,514 assembled unique transcripts from flowers, flower
      pedicels and pods undergoing abscission and from control organs. Comparison of
      the cDNA libraries from dropped and control organs helped in identifying 1,343,
      2,933 and 1,491 differentially expressed genes (DEGs) in the flowers, flower
      pedicels and pods, respectively. In DEG analyses, we focused on genes involved in
      phytohormonal regulation, cell wall functioning and metabolic pathways. Our
      results indicate that auxin, ethylene and gibberellins are some of the main
      factors engaged in generative organ abscission. Identified 28 DEGs common for all
      library comparisons are involved in cell wall functioning, protein metabolism,
      water homeostasis and stress response. Interestingly, among the common DEGs we
      also found an miR169 precursor, which is the first evidence of micro RNA engaged
      in abscission. A KEGG pathway enrichment analysis revealed that the identified
      DEGs were predominantly involved in carbohydrate and amino acid metabolism, but
      some other pathways were also targeted. This study represents the first
      comprehensive transcriptome-based characterization of organ abscission in L.
      luteus and provides a valuable data source not only for understanding the
      abscission signaling pathway in yellow lupine, but also for further research
      aimed at improving crop yields.

PMID- 28512466
TI  - Salinity Stress Does Not Affect Root Uptake, Dissemination and Persistence of
      Salmonella in Sweet-basil (Ocimum basilicum).
AB  - Crop produce can be contaminated in the field during cultivation by bacterial
      human pathogens originating from contaminated soil or irrigation water. The
      bacterial pathogens interact with the plant, can penetrate the plant via the root
      system and translocate and survive in above-ground tissues. The present study is
      first to investigate effects of an abiotic stress, salinity, on the interaction
      of plants with a bacterial human pathogen. The main sources of human bacterial
      contamination of plants are manures and marginal irrigation waters such as
      treated or un-treated wastewater. These are often saline and induce
      morphological, chemical and physiological changes in plants that might affect the
      interaction between the pathogens and the plant and thereby the potential for
      plant contamination. This research studied effects of salinity on the
      internalization of the bacterial human pathogen Salmonella enterica serovar
      Newport via the root system of sweet-basil plants, dissemination of the bacteria
      in the plant, and kinetics of survival in planta. Irrigation with 30 mM NaCl
      salinity induced typical salt-stress effects on the plant: growth was reduced, Na
      and Cl concentrations increased, K and Ca concentrations reduced, osmotic
      potential and anti-oxidative activity were increased by 30%, stomatal conductance
      was reduced, and concentrations of essential-oils in the plants increased by 26%.
      Despite these physical, chemical and morphological changes in the plants, root
      internalization of the bacteria and its translocation to the shoot were not
      affected, and neither was the die-off rate of Salmonella in planta. The results
      demonstrate that the salinity-induced changes in the sweet-basil plants did not
      affect the interaction between Salmonella and the plant and thereby the potential
      for crop contamination.

PMID- 28512468
TI  - Molecular Identification and Karyological Analysis of a Rampant Aspen Populus
      tremula L. (Salicaceae) Clone.
AB  - A rampant highly heterozygous aspen (Populus tremula L.) clone "Meshabash" has
      been revealed in course of population genetic diversity analysis in a native
      stand in the Republic of Tatarstan, Russia. Here we report the results of
      karyological analysis showing that this highly vigorous clone is diploid (2n =
      38) while typically triploid aspen demonstrates increased growth rate and
      resistance to aspen trunk rot caused by fungus Phellinus tremulae. By means of
      DNA identification of a series of model trees using 14 SSR loci we outlined the
      area occupied by this clone (at least 1.94 ha) and demonstrated that its ramets
      constitute 40 out of 48 genotyped trunks on the plot with the maximal distance
      between ramets 254 m. Since aspen is able to regenerate after cutting or die-off
      of maternal tree by root suckers at a distance up to 20-35 m this assumed that
      current stand appeared as a result of such spreading from an ortet tree during at
      least 5 generations. Trunk rot damage in the wood of model trees indicated low
      influence of this pathogen on viability and performance of the studied clone that
      can be associated with its extreme heterozygosity level (0.926) exceeding all the
      studied trees in this research plot and in three other control samples.

PMID- 28512467
TI  - Extra Facial Landmark Localization via Global Shape Reconstruction.
AB  - Localizing facial landmarks is a popular topic in the field of face analysis.
      However, problems arose in practical applications such as handling pose
      variations and partial occlusions while maintaining moderate training model size
      and computational efficiency still challenges current solutions. In this paper,
      we present a global shape reconstruction method for locating extra facial
      landmarks comparing to facial landmarks used in the training phase. In the
      proposed method, the reduced configuration of facial landmarks is first
      decomposed into corresponding sparse coefficients. Then explicit face shape
      correlations are exploited to regress between sparse coefficients of different
      facial landmark configurations. Finally extra facial landmarks are reconstructed
      by combining the pretrained shape dictionary and the approximation of sparse
      coefficients. By applying the proposed method, both the training time and the
      model size of a class of methods which stack local evidences as an appearance
      descriptor can be scaled down with only a minor compromise in detection accuracy.
      Extensive experiments prove that the proposed method is feasible and is able to
      reconstruct extra facial landmarks even under very asymmetrical face poses.

PMID- 28512470
TI  - Predictors of Cephalic Vaginal Delivery Following External Cephalic Version: An
      Eight-Year Single-Centre Study of 447 Cases.
AB  - Introduction. Our study aims to investigate and evaluate (1) rates of success of
      ECV for breech presentation at term at the Royal Women's Hospital in comparison
      to international standards; (2) mode of delivery following ECV; (3) factors
      influencing success rates of ECV at the Royal Women's Hospital. Methods. An audit
      of all women who underwent ECV between the years 2007 and 2014 at the Royal
      Women's Hospital as public patients was completed. Data parameters were collected
      from paper and electronic patient files at the Women's Hospital. Data was
      collected to analyse the effect of the following parameters on ECV success and
      birth outcome: age, parity, gestational age, BMI, AFI, and tocolytic use. These
      parameters were analysed to determine their effect on ECV outcome and birth
      outcome. Results. The Women's Hospital, Melbourne, has an ECV success rate of
      approximately 37%. Of the patients undergoing ECV, 29% proceeded to normal
      vaginal delivery. Predictors of successful ECV included low BMI, multiparity, and
      AFI more than 16 (P < 0.05). The only predictor of cephalic vaginal delivery
      following ECV was multiparity. Negative predictors of cephalic delivery were low
      AFI and nulliparity. Conclusions. The success rate of ECV at the Women's
      Hospital, Melbourne, is in line with global standards.

PMID- 28512469
TI  - Metabolic Perturbation and Potential Markers in Patients with Esophageal Cancer.
AB  - Clinical diagnosis of esophageal cancer (EC) at early stage is rather difficult.
      This study aimed to profile the molecules in serum and tissue and identify
      potential biomarkers in patients with EC. A total of 64 volunteers were
      recruited, and 83 samples (24 EC serum samples, 21 serum controls, 19 paired EC
      tissues, and corresponding tumor-adjacent tissues) were analyzed. The gas
      chromatography time-of-flight mass spectrometry (GC/TOF-MS) was employed, and
      principal component analysis was used to reveal the discriminatory metabolites
      and identify the candidate markers of EC. A total of 41 in serum and 36
      identified compounds in tissues were relevant to the malignant prognosis. A
      marked metabolic reprogramming of EC was observed, including enhanced anaerobic
      glycolysis and glutaminolysis, inhibited tricarboxylic acid (TCA) cycle, and
      altered lipid metabolism and amino acid turnover. Based on the potential markers
      of glucose, glutamic acid, lactic acid, and cholesterol, the receiver operating
      characteristic (ROC) curves indicated good diagnosis and prognosis of EC. EC
      patients showed distinct reprogrammed metabolism involved in glycolysis, TCA
      cycle, glutaminolysis, and fatty acid metabolism. The pivotal molecules in the
      metabolic pathways were suggested as the potential markers to facilitate the
      early diagnosis of human EC.

PMID- 28512471
TI  - Resveratrol Induces Differentiation of Human Umbilical Cord Mesenchymal Stem
      Cells into Neuron-Like Cells.
AB  - Objective. Human umbilical cord mesenchymal stem cells (hUC-MSCs) potentially
      differentiate to various types of cells including neuron-like cells. The natural
      polyphenol resveratrol benefits patients with many diseases including ischemic
      brain injury. We hypothesize that resveratrol induces differentiation of hUC-MSCs
      into neuron-like cells. Methods. Flow cytometry was used to determine the surface
      antigens in different stage of hUC-MSCs (P2, P5, and P10). Nestin, neuron
      specific enolase (NSE), and glial fibrillary acidic protein (GFAP) were detected
      by immunocytochemistry, Western blotting, and real time RT-PCT. The cultured hUC
      MSCs were treated with resveratrol at different concentrations (0, 7.5, 15.0, and
      30.0 mg/L). Nestin, GFAP, and NSE protein and mRNA were measured at posttreatment
      time points of 2 h, 4 h, 6 h, 12 h, and 24 h. Results. Neuron-like cells were
      found in hUC-MSCs treated by resveratrol at concentrations of 15.0 and 30.0 mg/L,
      but not in hUC-MSCs treated with vehicle and 7.5 mg/L resveratrol. Furthermore,
      immunocytochemical staining revealed that nestin and NSE immunoreactivities were
      positive in resveratrol-treated hUC-MSCs at concentrations of 15.0 and 30.0 mg/L.
      Resveratrol treatment significantly increased nestin and NSE protein and mRNA
      levels 4 h after the treatment. However, resveratrol treatment did not change
      GFAP immunoreactivities and protein and mRNA expression levels in cultured hUC
      MSCs. Conclusions. Taken together, resveratrol treatment induces a
      differentiation of hUC-MSCs into neuron-like cells at relatively high
      concentrations.

PMID- 28512472
TI  - Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF
      beta Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast
      Differentiation.
AB  - Pulsed electromagnetic fields (PEMFs) have been documented to promote bone
      fracture healing in nonunions and increase lumbar spinal fusion rates. However,
      the molecular mechanisms by which PEMF stimulates differentiation of human bone
      marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this
      study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF
      stimulation of hBMSCs' cell numbers mainly affected genes of cell cycle
      regulation, cell structure, and growth receptors or kinase pathways. In the
      differentiation and mineralization stages, PEMF regulated preosteoblast gene
      expression and notably, the transforming growth factor-beta (TGF-beta) signaling
      pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated
      activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and
      TGF-beta signaling was essential for PEMF stimulation of alkaline phosphatase
      mRNA expression. Smad7, an antagonist of the TGF-beta signaling pathway, was
      found to be miR21-5p's putative target gene and PEMF caused a decrease in Smad7
      expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p
      inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating
      cells. Thus, PEMF could mediate its effects on bone metabolism by activation of
      the TGF-beta signaling pathway and stimulation of expression of miR21-5p in
      hBMSCs.

PMID- 28512474
TI  - Human Papillomavirus Genotype Distribution among Cervical Cancer Patients prior
      to Brazilian National HPV Immunization Program.
AB  - To evaluate the impact of HPV immunization and possible changes in virus type
      specific prevalence associated with cervical cancer, it is important to obtain
      baseline information based on socioeconomic, educational, and environmental
      characteristics in human populations. We describe these characteristics and the
      type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in
      two Brazilian healthcare institutions located at the Southeastern (Rio de
      Janeiro/RJ) and the Amazonian (Belem/PA) regions. Large differences were observed
      between women in these regions regarding economic, educational, and reproductive
      characteristics. The eight most frequent HPV types found in tumor samples were
      the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as
      unknown or low risk were found in tumor samples with single infections, HPV 83 in
      RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was
      lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more
      frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16
      in PA was higher in younger women (p < 0.05). The success of a cervical cancer
      control program should consider HPV types, local health system organization, and
      sociodemographic diversity of Brazilian regions.

PMID- 28512475
TI  - Risk Factors for Road Traffic Injuries among Different Road Users in the Gambia.
AB  - We identified risk factors for road traffic injuries among road users who
      received treatment at two major trauma hospitals in urban Gambia. The study
      includes pedestrians, bicyclists, motorcyclists, and drivers/passengers of cars
      and trucks. We examined distributions of injury by age, gender, collision vehicle
      types and vehicle category, and driver and environment factors. Two hundred and
      fifty-four patients were included in the study. Two-thirds were male and one
      third female. Two-thirds (67%) of road traffic injuries involved pedestrians,
      bicyclists, and motorcyclists; and these were more common during weekdays (74%)
      than weekends. Nearly half (47%) of road traffic injuries involved pedestrians.
      One-third (34%) of injured patients were students (mean age of students was less
      than 14 years), more than half (51%) of whom were injured on the roadway as
      pedestrians. Head/skull injuries were common. Concussion/brain injuries were 3.5
      times higher among pedestrians, bicyclists, and motorcyclists than vehicle
      occupants. Crashes involving pedestrians were more likely to involve young people
      (<25 years; aOR 6.36, 95% CI: 3.32-12.17) and involve being struck by a motor car
      (aOR 3.95, 95% CI: 2.09-7.47). Pedestrians contribute the largest proportion of
      hospitalizations in the Gambia. Young pedestrians are at particularly high risk.
      Prevention efforts should focus on not only vehicle and driver factors, but also
      protecting pedestrians, bicyclists, and motorcyclists.

PMID- 28512476
TI  - Root and Canal Morphology of Mandibular Molars in a Selected Iranian Population
      Using Cone-Beam Computed Tomography.
AB  - INTRODUCTION: The aim of this study was to evaluate the root canal morphology of
      mandibular first and second molars using cone-beam computed tomography (CBCT) in
      northern Iranian population and also to indicate the thinnest area around root
      canals. METHODS AND MATERIALS: We evaluated CBCT images of 154 first molars and
      147 second molars. By evaluating three axial, sagittal and coronal planes of each
      tooth we determined the number of root canals, prevalence of C-shaped Melton
      types, and prevalence of Vertucci configuration and inter orifice distance. Also
      the minimum wall thickness of root canals was determined by measuring buccal,
      lingual, distal and mesial wall thicknesses of each canal in levels with 2 mm
      intervals from apex to orifice. RESULTS: Amongst 154 first mandibular molars, 149
      (96.7%) had two roots, 3 (1.9%) had three roots and 2 (1.2%) had C-shaped root
      configuration. Of 147 second mandibular molars, 120 (81.6%) had two roots, 1
      (0.6%) had three roots and 26 (17.6%) had C-shaped roots. There was no
      significant difference in the prevalence of Vertucci's type between two genders.
      The most common configuration in mesial roots of first and second molars were
      type IV (57%-42.9%) and type II (31.5%-28%). Mesial and distal walls had the most
      frequency as the thinnest wall in all levels of root canals with mostly less than
      1 mm thickness. In second molars the DB-DL inter orifice distance and in first
      molars the MB-ML distance were the minimum. MB-D in first molars had the maximum
      distance while ML-DL, MB-DB and ML-D had the same and maximum distance in second
      molars. CONCLUSION: Vertucci's type IV and type I were the most prevalent
      configurations in mesial and distal roots of first and second mandibular molars
      and the thickness of thinnest area around the canals should be considered during
      endodontic treatments.

PMID- 28512477
TI  - Physical Properties and Chemical Characterization of Two Experimental Epoxy Resin
      Root Canal Sealers.
AB  - INTRODUCTION: The aim of this in vitro study was to evaluate the setting time,
      flow, film thickness, solubility, radiopacity and characterization analysis of
      three epoxy resin based sealers including two experimental sealers and AH-26.
      METHODS AND MATERIALS: Five samples of each material were evaluated for setting
      time, flow, film thickness, solubility and radiopacity according to ISO 6876
      Standard. Characterization of sealers was performed under the scanning electron
      microscopy (SEM), X-ray energy dispersive spectroscopy, X-ray diffraction (XRD)
      and Fourier transform infrared (FTIR) spectroscopy. Statistical evaluation was
      performed using the Kruskal-Wallis test. RESULTS: In this study, AH-26 showed
      more radiopacity and flow compared to two other experimental sealers (P<0.05).
      However, both sealers had lower setting time than AH-26 (P<0.05). No statistical
      differences were found regarding film thickness, solubility and radiopacity
      (P>0.05). The characterization analysis exhibited relatively similar
      microstructure of AH-26 sealer to the experimental root canal sealers.
      CONCLUSION: According to the result of this study, all tested root canal sealers
      had acceptable properties based on ISO 6876 standard criteria.

PMID- 28512473
TI  - Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and
      Epigenetics.
AB  - Transcription factors and signaling molecules are well-known regulators of stem
      cell identity and behavior; however, increasing evidence indicates that
      environmental cues contribute to this complex network of stimuli, acting as
      crucial determinants of stem cell fate. l-Ascorbic acid (vitamin C (VitC)) has
      gained growing interest for its multiple functions and mechanisms of action,
      contributing to the homeostasis of normal tissues and organs as well as to tissue
      regeneration. Here, we review the main functions of VitC and its effects on stem
      cells, focusing on its activity as cofactor of Fe+2/alphaKG dioxygenases, which
      regulate the epigenetic signatures, the redox status, and the extracellular
      matrix (ECM) composition, depending on the enzymes' subcellular localization.
      Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum,
      VitC regulates ECM/collagen homeostasis and plays a key role in the
      differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and
      tendons. In the nucleus, VitC enhances the activity of DNA and histone
      demethylases, improving somatic cell reprogramming and pushing embryonic stem
      cell towards the naive pluripotent state. The broad spectrum of actions of VitC
      highlights its relevance for stem cell biology in both physiology and disease.

PMID- 28512478
TI  - Subcutaneous Reaction of Rat Tissues to Nanosilver Coated Gutta-Percha.
AB  - INTRODUCTION: Gutta-percha (GP), is a neutral and non-toxic material. The aim of
      this animal study was to compare the biocompatibility of nanosilver coated GP (NS
      GP) with conventional GP in subcutaneous tissues in a rat model. METHODS AND
      MATERIALS: Conventional GP and NS-GP were subcutaneously implanted in the backs
      of 20 male Wistar rats (n=10). A control animal was assigned for each trial
      period. Ten animals were sacrificed after 7 and 30 days and light microscopic
      evaluation of tissue reaction to NS-GP (n=20) and conventional GP (n=20) was
      accomplished. The Mann-Whitney U, Wilcoxon Signed Ranks, Fisher Exact, and
      McNemar tests were used for statistical analysis of the data. RESULTS: After 7
      days, inflammation was moderate and mild for NS-GP and conventional GP,
      respectively (P<0.001). After 30 days, no inflammation was discernible in
      conventional GP. However, mild inflammation was reported for NS-GP (P<0.001).
      Regarding inflammatory cell type, there was a significant difference between two
      experimental groups at both times (P<0.001). CONCLUSION: Inflammation decreased
      over time in both groups. Fibrous connective tissue, a representative of healing
      and control of inflammatory process, surrounded both test materials. NS-GP was
      biocompatible and might be a reasonable endodontic obturation material.

PMID- 28512479
TI  - In vitro Cytotoxicity Comparison of MTA Fillapex, AH-26 and Apatite Root Canal
      Sealer at Different Setting Times.
AB  - INTRODUCTION: This study aimed to compare the cytotoxicity of MTA Fillapex, AH-26
      and Apatite root canal sealers at different times after mixing. METHODS AND
      MATERIALS: In this in vitro study, MTA Fillapex, AH-26 and Apatite root canal
      sealer were spilled uniformly by 40 um mesh in a 96-well plate. Then, human fetal
      foreskin fibroblast cell line (HFFF2) were added to each sealer cell culture
      medium. Cytotoxicity was measured using MTT assay after 24, 48 and 72 h and seven
      days. Multiple comparisons were done using analysis of variances (ANOVA) and
      Scheffe's post hoc test. RESULTS: All studied sealers exhibited severe
      cytotoxicity (more than 70%) except for Apatite sealer (95%) at 48 h after
      mixing. Cytotoxicity of MTA Fillapex and AH-26 were similar (P>0.05) at 24, 48
      and 72 h and 7 days after mixing of sealers. Cytotoxicity of MTA Fillapex and
      Apatite root canal sealer, at 24 and 48 h, were significantly different (P=0.003
      and P=0.000, respectively); MTA Fillapex was more cytotoxic. However in 72 h and
      7 days after mixing, the difference was not significant (P>0.05). At 24 and 48 h
      after mixing, AH-26 was more cytotoxic (P=0.002 and P=0.000, respectively). Same
      as above at 72 h and 7 days after mixing, their cytotoxicity were similar
      (P>0.05). CONCLUSION: Overall cytotoxicity of all studied materials were severe.
      However, it was observed that the cytotoxicity of MTA Fillapex, AH-26 and Apatite
      root canal sealer decreased over time. Apatite root canal sealer exhibited the
      least cytotoxicity. Cytotoxicity of MTA Fillapex and AH-26 were similar at
      different time intervals.

PMID- 28512480
TI  - Effect of Intra-Canal Calcium Hydroxide Remnants on the Push-Out Bond Strength of
      Two Endodontic Sealers.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of intra-canal
      calcium hydroxide (CH) remnants after ultrasonic irrigation and hand file removal
      on the push out bond strength of AH-26 and EndoSequence Bioceramic sealer (BC
      Sealer). METHODS AND MATERIALS: A total of 102 single-rooted extracted human
      teeth were used in this study. After root canal preparation up to 35/0.04 Mtwo
      rotary file, all the specimens received CH dressing except for 34 specimens in
      the control group. After 1 week, the specimens with CH were divided into 2 groups
      (n=34) based on the CH removal technique; i.e. either with ultrasonic or with #35
      hand file. Then specimens were divided into two subgroups according to the sealer
      used for root canal obturation: AH-26 or BC Sealer. After 7 days, 1 mm-thick
      disks were prepared from the middle portion of the specimens. The push out bond
      strength and failure mode were evaluated. Data were analyzed by the two-way ANOVA
      and Tukey's post hoc tests. RESULTS: The push out bond strength of both sealers
      was lower in specimens receiving CH. These values were significantly higher when
      CH was removed by ultrasonic (P<0.05). The dominant mode of failure in all
      subgroups was of mixed type except for the BC Sealer specimens undergoing CH
      removal with hand file which dominantly exhibited adhesive mode of failure.
      CONCLUSION: CH remnants had a negative effect on the push out bond strength of AH
      26 and BC Sealer. Ultrasonic irrigation was more effective in removing CH.

PMID- 28512481
TI  - Influence of Root Canal Curvature on the Accuracy of Root ZX Electronic Foramen
      Locator: An In Vitro Study.
AB  - INTRODUCTION: The aim of this in vitro study was to evaluate the correlation
      between accuracy of Root ZX electronic foramen locator and root canal curvature.
      METHODS AND MATERIALS: One hundred and ten extracted mandibular molars were
      selected. Access cavity was prepared and coronal enlargement of mesiobuccal canal
      was performed. A #10 Flexofile was inserted into the mesiobuccal canal, and a
      radiography was taken to measure the degree of curvature by Schneider's method.
      The actual working length (AWL) was defined by inserting the file until its tip
      could be observed at a place tangential to the major apical foramen and then 0.5
      mm was subtracted from this measurement. For the electronic working length (EWL)
      measurement, the apical 3 or 4 mm of the root was embedded in alginate as the
      electrolyte material. The file was inserted into the root canal to the major
      foramen, until the APEX reading was shown on the electronic device and then
      pulled back until the visual display showed the 0.5-mm mark. The AWL was
      subtracted from the EWL to define the distance between the file tip and the point
      0.5 mm coronal to the major apical foramen. Data were analyzed using the
      Pearson's correlation coefficient. RESULTS: The accuracy of Root ZX within +/-0.1
      mm and +/-0.5 mm was 38.2% and 94.6%, respectively. There was no correlation
      between the distance from the EWL to the AWL and the degree of root canal
      curvature (r=0.097, P=0.317). CONCLUSION: Root canal curvature did not influence
      the accuracy of Root ZX foramen locator.

PMID- 28512482
TI  - Effect of Field Of View on Detection of External Root Resorption in Cone-Beam
      Computed Tomography.
AB  - INTRODUCTION: Conventional methods for diagnosis of external root resorption
      (ERR) are based on clinical findings and x-ray observations which are not
      appropriate for early diagnosis. The present study assessed the effect of
      different sizes and field of views (FOVs) in the diagnosis of simulated external
      root resorption by cone-beam computed tomography (CBCT). METHODS AND MATERIALS:
      In this diagnostic in vitro trial, 100 human extracted mandibular central
      incisors were collected and marked in 3 apical, middle and coronal areas.
      Cavities with different sizes were created in buccal and lingual surfaces of each
      area. Following this procedure, CBCT images were taken in 2 different 6 * 6 cm
      and 12 * 8 cm FOVs with the same voxel size of 0.2 mm. Absence or presence of
      cavities in CBCT images were assigned by 3 radiologists and compared with gold
      standard results which were obtained by measurement of the size of cavities using
      a digital caliper. Sensitivity and specificity values, positive predictive value
      (PPV) and negative predictive value (NPV), AZ value and Kappa values were
      calculated and reported. RESULTS: Amounts of sensitivity in 6 * 6 cm FOV with
      voxel size of 0.2 mm for small, medium and large cavities were 95.93%, 96.03% and
      97.1%, respectively. Amounts of sensitivity in 12 * 8cm FOV with the same voxel
      size for small, medium and large cavities were noted as 94.4%, 96.03% and 98.5%,
      respectively. However, specificity in FOV of 6 * 6 cm and FOV of 12 * 8 cm was
      calculated as 93.03% and 90.83%, respectively. CONCLUSION: Both used FOVs show
      nearly same performances in the case of detection of ERR; therefore, smaller FOV
      should be preferably used for detection of ERR in order to decrease the amount of
      imposed radiation dose given to patients.

PMID- 28512483
TI  - Efficacy of Different Root Canal Irrigants on Smear Layer Removal after Post
      Space Preparation: A Scanning Electron Microscopy Evaluation.
AB  - INTRODUCTION: Effective durable adhesion between post material and dentine using
      resin cements is essential for longevity of restoration. The aim of this in vitro
      study was to compare the effect of different irrigants on smear layer removal
      after post space preparation. METHODS AND MATERIALS: A total of 75 extracted
      anterior human teeth were selected. The canals were instrumented by rotary system
      and then were filled. After preparing the post space, teeth were divided into 5
      groups according to irrigants: 17% EDTA; 17% EDTA+2% CHX; 5.25% NaOCl; 17%
      EDTA+5.25% NaOCl; and saline. The canals were irrigated with 5 cc of each
      irrigants for 1 min. Specimens were examined with scanning electron microscopy
      (SEM). Hulsmann's score was used for marking of smear layer removal at coronal,
      middle and apical thirds of post space. The data were analyzed using the Kruskal
      Wallis and Mann-Whitney U tests. RESULTS: The results revealed that subsequent
      use of 17% EDTA+5.25% NaOCl was more effective than the other groups in smear
      layer removal. No statistical difference was found among different levels of root
      canal within each group. CONCLUSION: It can be concluded that 17% EDTA+5.25%
      NaOCl could be an effective irrigant for smear layer removal after post space
      preparation.

PMID- 28512484
TI  - Scanning Electron Microscopy and Energy-Dispersive X-Ray Microanalysis of Set CEM
      Cement after Application of Different Bleaching Agents.
AB  - INTRODUCTION: The present study evaluated the element distribution in completely
      set calcium-enriched mixture (CEM) cement after application of 35% carbamide
      peroxide, 40% hydrogen peroxide and sodium perborate as commercial bleaching
      agents using an energy-dispersive x-ray microanalysis (EDX) system. The surface
      structure was also observed using the scanning electron microscope (SEM). METHODS
      AND MATERIALS: Twenty completely set CEM cement samples, measuring 4*4 mm2, were
      prepared in the present in vitro study and randomly divided into 4 groups based
      on the preparation technique as follows: the control group; 35% carbamide
      peroxide group in contact for 30-60 min for 4 times; 40% hydrogen peroxide group
      with contact time of 15-20 min for 3 times; and sodium perborate group, where the
      powder and liquid were mixed and placed on CEM cement surface 4 times. Data were
      analyzed at a significance level of 0.05 through the one Way ANOVA and Tukey's
      post hoc tests. RESULTS: EDX showed similar element distribution of oxygen,
      sodium, calcium and carbon in CEM cement with the use of carbamide peroxide and
      hydroxide peroxide; however, the distribution of silicon was different (P<0.05).
      In addition, these bleaching agents resulted in significantly higher levels of
      oxygen and carbon (P<0.05) and a lower level of calcium (P<0.05) compared to the
      control group. SEM of the control group showed plate-like and globular structure.
      Sodium perborate was similar to control group due to its weak oxidizing
      properties. Globular structures and numerous woodpecker holes were observed on
      the even surface on the carbamide peroxide group. CONCLUSION: The mean elemental
      distribution of completely set CEM cement was different when exposed to sodium
      perborate, carbamide peroxide and hydrogen peroxide.

PMID- 28512485
TI  - Effect of Blood Exposure on Push-Out Bond Strength of Four Calcium Silicate Based
      Cements.
AB  - INTRODUCTION: The purpose of this study was to compare the push-out bond strength
      of white ProRoot Mineral Trioxide Aggregate (MTA), Biodentine, calcium-enriched
      mixture (CEM) cement and Endosequence Root Repair Material (ERRM) putty after
      exposure to blood. METHODS AND MATERIALS: A total of 96 root dentin slices with a
      standardized thickness of 1.00+/-0.05 mm and standardized canal spaces were
      randomly divided into 4 main experimental groups (n=24) according to the calcium
      silicate based cement (CSC) used: white ProRoot MTA, CEM Cement, ERRM Putty and
      Biodentine. Specimens were exposed to whole fresh human blood and then subdivided
      into two subgroups depending on the exposure time (24 or 72 h). Push-out bond
      strength was measured using a universal testing machine. Failure modes were
      examined under a light microscope under *10 magnification. Data were analyzed
      using the two-way ANOVA test. RESULTS: Biodentine exhibited the highest values
      regardless of the exposure time. The lowest push-out strength values were seen in
      white ProRoot MTA and CEM cement in both post exposure times. After exposure to
      blood, the push-out bond strength of all materials increased over time. This
      increase was only statistically significant in white ProRoot MTA and ERRM
      specimens. The dominant failure mode in all CSCs was the adhesive mode.
      CONCLUSION: Biodentine showed the highest values of push-out bond strength and
      may be better options for situations encountering higher dislocation forces in a
      short time after cement application.

PMID- 28512487
TI  - Comparative Antimicrobial Efficacy of Eucalyptus Galbie and Myrtus Communis L.
      Extracts, Chlorhexidine and Sodium Hypochlorite against Enterococcus Faecalis.
AB  - INTRODUCTION: The aim of this study was to evaluate the antimicrobial effect of
      Eucalyptusgalbie and Myrtus communis L. methanolic extracts, chlorhexidine (CHX)
      and sodium hypochlorite (NaOCl) on Enterococcus faecalis (E. faecalis) as the
      predominant species isolated from infected root canals. METHODS AND MATERIALS:
      One hundred twenty mandibular premolars were randomly divided into 8 groups:
      Eucalyptusgalbie (E. galbie) 12.5 mg/mL, Myrtus communis L. (M. communis L.) 6.25
      mg/mL, 0.2% CHX, %2 CHX, 2.5% NaOCl, 5.25% NaOCl, positive and negative control
      group. Sampling was performed using paper points (from the root canal space
      lumen) and Gates-Glidden drills (from the dentinal tubules); then colony forming
      units (CFU) were counted and analyzed using the Kruskal-Wallis test, followed by
      Mann Whitney U test. The level of significance was set at 0.05. RESULTS: All
      irrigants reduced more than 99% of bacteria in root canal. In the presence of M.
      communis L. and E. galbie, the bacterial count in dentin were significantly more
      than CHX and NaOCl groups (P<0.05) except 0.2% CHX in 200 um and 400 um depths
      (P>0.05). CONCLUSION: Although 5.25% NaOCl was the most effective irrigant, all
      agents exerted acceptable antimicrobial activity against E. faecalis.

PMID- 28512486
TI  - Students' Knowledge Comprehension after Implementation of Live Conventional
      Demonstration, Video Teaching and Video-Assisted Instruction Methods in
      Endodontic Practice.
AB  - INTRODUCTION: Video-assisted clinical instruction (VACID) has been found to be a
      beneficial teaching tool for various fields in dentistry. The aim of this
      interventional study was to compare the efficacy of live conventional
      demonstration (CD), video teaching, and VACID (video with explanation) methods in
      teaching of root canal treatment to undergraduate dental students. METHODS AND
      MATERIALS: Forty-two undergraduate senior dental students participated in this
      study. The students experienced this course for the first time and were randomly
      divided into three groups (n=14). Group A attended live CD on a patient; group B
      watched a professionally produced demonstration video without any verbal
      explanation during 1 h; and finally group C watched the same video alongside live
      explanation by a mentor during the 1.5 h (VACID). The whole process was performed
      by an experienced endodontist on maxillary central incisors. All of The students
      carried out a multiple choice question exam to evaluate their comprehension. The
      mean score of the experimental groups were compared using ANOVA test and multiple
      comparisons were carried out with Tamhane test. The level of significance was set
      at 0.05. RESULTS: There was significant difference among three groups according
      to the ANOVA test (P<0.05). Group VACID had the highest mean scores. There was
      significant difference between the groups VACID and VT (P=0.011); no significant
      differences were found in other inter-group comparisons. CONCLUSION: According to
      the results, VACID may improve the quality of endodontic training in
      undergraduate dental students.

PMID- 28512488
TI  - In Vitro Microleakage of Mineral Trioxide Aggregate, Calcium-Enriched Mixture
      Cement and Biodentine Intra-Orifice Barriers.
AB  - INTRODUCTION: This in vitro study compared the coronal microleakage of mineral
      trioxide aggregate (MTA), calcium-enriched mixture (CEM) cement and Biodentine as
      intra-orifice barriers. METHODS AND MATERIALS: The study was conducted on 76
      extracted single-canal human teeth. Their root canals were prepared using
      ProTaper rotary files and filled with gutta percha and AH-26 sealer using lateral
      condensation technique. Coronal 3 mm of the gutta percha was removed from the
      root canals and replaced randomly with MTA, CEM cement or Biodentine in the three
      experimental groups (n=22). A positive and a negative control group were also
      included (n=5). The entire root surfaces of all teeth were covered with two
      layers of nail varnish in such a way that only the access openings were not
      coated. In the negative control group, the access opening was also coated with
      nail varnish. All teeth were immersed in India ink and after clearing, the
      samples were evaluated under a stereomicroscope under *10 magnification to assess
      the degree of dye penetration. The data were analyzed using the Kruskal-Wallis
      test. The level of significance was set at 0.05. RESULTS: The negative control
      group showed no leakage while the positive control group showed significantly
      higher microleakage than the test groups (P>0.05). CEM cement had the lowest
      (0.175+/-0.068 mm) and MTA showed the highest dye penetration (0.238+/-0.159 mm)
      among the experimental groups; although these differences were not statistically
      significant (P=0.313). CONCLUSION: CEM cement exhibited the least microleakage as
      an intra-orifice barrier in endodontically treated teeth.

PMID- 28512489
TI  - Effect of Deep Cryogenic Treatment on Cyclic Fatigue of Endodontic Rotary Nickel
      Titanium Instruments.
AB  - INTRODUCTION: Cyclic fatigue is the common reason for breakage of rotary
      instruments. This study was conducted to evaluate the effect of cryogenic
      treatment (CT) in improving the resistance to cyclic fatigue of endodontic rotary
      instruments. METHODS AND MATERIALS: In this in vitro study, 20 RaCe and 20 Mtwo
      files were randomly divided into two groups of negative control and CT. CT files
      were stored in liquid nitrogen at -196 degrees C for 24 h, and then were
      gradually warmed to the room temperature. All files were used (at torques and
      speeds recommended by their manufacturers) in a simulated canal with a 45 degrees
      curvature until breakage. The time to fail (TF) was recorded and used to
      calculate the number of cycle to fail (NCF). Groups were compared using
      independent-samples t-test. RESULTS: Mean NCFs were 1248.2+/-68.1, 1281.6+/-78.6,
      4126.0+/-179.2, and 4175.4+/-190.1 cycles, for the Mtwo-control, Mtwo-CT, RaCe
      control, and RaCe-CT, respectively. The difference between the controls and their
      respective CT groups were not significant (P>0.3). The difference between the
      systems was significant. CONCLUSION: Deep CT did not improve resistance to cyclic
      fatigue of the evaluated rotary files.

PMID- 28512490
TI  - In Vitro Cytotoxicity of a New Nano Root Canal Sealer on Human Gingival
      Fibroblasts.
AB  - INTRODUCTION: The aim of this in vitro study was to evaluate the cytotoxicity of
      a new nano zinc-oxide eugenol (NZOE) sealer on human gingival fibroblasts (HGFs)
      compared with Pulpdent (micro-sized ZOE sealer) and AH-26 (resin-based sealer).
      METHODS AND MATERIALS: The Pulpdent, AH-26, and NZOE sealers were prepared and
      exposed to cell culture media immediately after setting, and 24 h and one week
      after setting. Then, the primary cultured HGFs were incubated for 24 h with
      different dilutions (1:1 to 1:32) of each sealer extract. Cell viability was
      evaluated by methyl thiazolyl diphenyl tetrazolium bromide (MTT) assay. The
      results were compared using two-way analysis of variance followed by Tukey's post
      hoc test. The level of significance was set at 0.05. RESULTS: All sealer
      extracts, up to 32 times dilutions, showed cytotoxicity when exposed to HGF
      immediately after setting. The extracts obtained 24 h or one week after setting
      showed lower cytotoxicity than extracts obtained immediately after setting. At
      all setting times, NZOE showed lower cytotoxicity than Pulpdent and AH-26. While
      one-week extracts of NZOE had no significant effect on the viability of HGF at
      dilutions 1:4 to 1:32, both Pulpdent and AH-26 decreased the cell viability at
      dilutions of 1:4 and 1:8. CONCLUSION: NZOE exhibited lower cytotoxicity compared
      to Pulpdent and AH-26 on HGF and has the potential to be considered as a new root
      canal filling material.

PMID- 28512491
TI  - Pulp Response following Direct Pulp Capping with Dentin Adhesives and Mineral
      Trioxide Aggregate; An Animal Study.
AB  - INTRODUCTION: Pulp vitality and its continuous dentin prodution are essential for
      long-term success of direct pulp capping (DPC). The aim of present study was to
      evaluate the histopathological response of the canine pulp following DPC using
      either different dentin adhesive resins (DAR), calcium hydroxide (CH) or mineral
      trioxide aggregate (MTA). METHODS AND MATERIALS: DPC was done on 72 dog's teeth
      using 6 types of dental materials (n=12) (4 types of DAR, white MTA and CH).
      Therefore, six healthy dogs were anesthetized and 2 teeth from each dog were
      allocated to either type of mentioned DPC agents. The dental pulps were exposed
      mechanically by drilling in the center of class V cavities. The different types
      of capping materials included DARS (Clearfil S3 Bond, Optibond FL, Single Bond
      and Clearfil SE Bond), white MTA and CH. After 7, 21 and 63 days, two dogs were
      euthanized in each interval. Microscopic evaluations were done according to
      following criteria: intensity of inflammation, presence of necrosis and formation
      of hard tissue. The recorded data were analyzed by the Kruskal-Wallis, Friedman,
      Cochran's and Fisher's exact tests using SPSS software version 12 at significant
      level of 0.05. RESULTS: No significant differences were found regarding necrosis
      among DPC materials (P>0.05). However, MTA caused higher amount of hard tissue
      formation after 63 days in comparison with 21 days. CONCLUSION: MTA provided the
      highest degree of hard tissue formation after 63 days. However, further studies
      should be performed for administering a definitive material.

PMID- 28512492
TI  - In Vitro Sealing Properties of Calcium-Enriched Mixture and Mineral Trioxide
      Aggregate Orifice Barriers during Intra-Coronal Bleaching.
AB  - INTRODUCTION: This study aimed at evaluating the sealing properties of calcium
      enriched mixture (CEM) compared to mineral trioxide aggregate (MTA) as a cervical
      barriers in intra-coronal bleaching. METHODS AND MATERIALS: In this in vitro
      study, endodontic treatment was performed on 60 extracted human incisors and
      canines without canal calcification, caries, restorations, resorption or cracks.
      The teeth were then randomly divided into two experimental groups and two control
      groups (n=15). Then, CEM cement and MTA were applied as 3-mm intra-orifice
      barriers in the test groups; a mixture of sodium perborate and 30% hydrogen
      peroxide bleaching agents were placed within the pulp chamber for one week. Dye
      penetration method was used to evaluate the sealing ability of agents.
      Statistical analysis was performed using SPSS software. The Kendall coefficient
      was used to evaluate inter-observer agreement. The chi-squared test was used for
      statistical analysis. RESULTS: The results showed that the penetration rates of
      CEM and MTA were the same as positive control group, with no significant
      differences (P=0.673 and P=0.408, respectively). However, there was a significant
      difference between the negative control group and CEM and MTA groups (P=0.001 for
      both groups). In addition, the sealing ability of MTA and CEM cement were not
      significantly different (P=0.682). CONCLUSION: During intra-coronal bleaching
      procedures CEM cement can be used as a cervical barrier with sealing properties
      comparable to that of MTA.

PMID- 28512493
TI  - Radiographic Quality of Root Canal Obturation Performed By Fifth Year Students of
      Hamadan Dental School.
AB  - INTRODUCTION: The aim of this study was to assess the radiographic technical
      quality of root canal therapy performed by fifth year students of Dental School
      of Hamadan University of Medical Sciences from 2015 to 2016. METHODS AND
      MATERIALS: Four hundred and seventy records of root canal therapies were
      evaluated. Records with graphies taken as initial, master apical file (MAF),
      master apical cone (MAC) and final radiographs were included in the study and
      records of patient younger than 16 years and older than 68 years were excluded
      from further investigations. Lastly, 432 teeth were selected. Obturation length,
      canal tapering, quality and density of filling material were the variables
      investigated in the present study. Two independent investigators examined the
      radiographies using a magnifying lens (*2) and x-ray viewer. Data were analyzed
      using chi-square test. RESULTS: The technical quality of root filling performed
      by undergraduate dental students was classified as acceptable in 10.4% of cases.
      Moreover, 70.8% of teeth had adequate filling, 17.1% were underfilled and 12%
      were overfilled. The three groups were significantly different in terms of
      working length and taper quality. One hundred ninety four (44.9%) records had
      adequate taper and 109 (25%) records had adequate density. There was a
      significant association between teeth location and the length of obturation so
      that the probability of a successful treatment was higher in maxillary teeth.
      Furthermore, the rate of a proper length of obturation was higher among incisors
      than that of premolars and molars. CONCLUSION: The technical quality of root
      canal therapy performed by dental students in Hamadan University of medical
      sciences is not as acceptable as it should be. One of the most important factors
      in this regard is a high student/professor ratio.

PMID- 28512494
TI  - Cleanliness of Canal Walls following Gutta-Percha Removal with Hand Files, RaCe
      and RaCe plus XP-Endo Finisher Instruments: A Photographic in Vitro Analysis.
AB  - INTRODUCTION: Gutta-percha must be removed from the root canal space during
      retreatment to ensure a more favorable outcome. The aim of this study was to
      compare the efficacy of hand instruments, RaCe and RaCe plus XP-endo finisher
      instruments in removal of gutta-percha from root canal walls during retreatment.
      METHODS AND MATERIALS: Thirty single-rooted premolars were prepared, obturated,
      and divided into three groups according to retreatment method; in group 1,
      retreatment was carried out by hand instruments, while in groups 2 and 3
      retreatment was done using RaCe rotary files alone or accompanied by XP-endo
      finisher instruments, respectively. After retreatment, teeth were sectioned
      longitudinally and photographic images were taken. The amount of remaining gutta
      percha in coronal, middle and apical thirds was quantified using Image J
      software. The two-way ANOVA and post hoc Tukey's tests were used to analyze data.
      The level of significance was set at 0.05. RESULTS: RaCe cleaned the apical third
      significantly better than hand instrumentation. In the coronal third, RaCe+XP
      endo finisher was more effective than RaCe. RaCe+XP-endo finisher was more
      effective than hand instrumentation in the entire root canal. The amount of
      remaining gutta-percha was the least in the apical part and increased toward the
      coronal part with the use of XP-endo finisher (P<0.05). CONCLUSION: Rotary
      instrumentation was more effective in removing gutta-percha from the canal walls.
      Furthermore, use of XP-endo finisher file resulted in cleaner canal walls and was
      more effective in removing gutta-percha from the coronal toward the apical part
      of the canal.

PMID- 28512495
TI  - Endodontic Management of Open Apex Teeth Using Lyophilized Collagen Sponge and
      MTA Cement: Report of Two Cases.
AB  - Teeth with open apices, such as in immature teeth or those with apical root
      resorption are clinical cases with difficult immediate resolution. With the use
      of mineral trioxide aggregate (MTA) in dentistry, it was possible to optimize the
      treatment time of these cases by immediate placement of apical plug and the root
      canal filling. However, some negative effects can occur if MTA is extruded beyond
      the apex. To avoid this accident, it has been recommended to use of an apical
      matrix prior to placement of MTA. This study reports two clinical cases of apical
      plug placement in teeth with pulp necrosis and open apices. One case had an
      immature apex due to dental trauma and the other case had apical resorption due
      to the presence of endodontic infection in the root canal. MTA apical plug with
      approximately 4 mm thickness, was placed in the apical zone of the root and
      immediately the canal was obturated with gutta-percha and endodontic sealer.
      Follow-up evaluations showed clinical and radiographic evidence of success.

PMID- 28512496
TI  - Nonsurgical Management of a Large Periapical Lesion: A Case Report.
AB  - This case report describes the non-surgical management of a large cyst-like
      periapical lesion in the mandible of a 16-year-old female with the chief
      complaint of periodic swelling and pus drainage from the mandibular anterior
      region gingivae with no history of pain and traumatic accident in this area. Both
      mandibular central incisors had extensive caries. Root canals of both mandibular
      central incisors were filled with calcium hydroxide. After 10 days, endodontic
      therapy was carried out on both teeth. Clinical and radiographic re-evaluations
      at 3 and 12 months revealed progressing bone healing. This case report shows that
      appropriate diagnosis in combination with root canal treatment as a conservative
      non-surgical approach can lead to complete healing of large lesions without
      invasive treatments.

PMID- 28512497
TI  - Management of Perforating Idiopathic Internal Root Resorption.
AB  - This case report describes the endodontic treatment of an idiopathic perforated
      internal root resorption. A 24-year-old male Malay patient presented with
      internal root resorption of two of his anterior teeth. The medical history was
      non-contributory and he had no history of traumatic injury or orthodontic
      treatment. Cone-beam computed tomography (CBCT) determined the nature, location
      and severity of the resorptive lesion. Non-surgical root canal treatment of tooth
      #22 and combined non-surgical and surgical approach for tooth #11 were carried
      out using mineral trioxide aggregate (MTA) as the filling material. The clinical
      and radiographic examination three years after completion of treatment revealed
      evidences of periapical healing. The appropriate diagnosis and the treatment of
      internal root resorption allowed good healing of these lesions and maintained the
      tooth in function for as long as possible.

PMID- 28512499
TI  - Neuroprotective Effect of Fagopyrum dibotrys Extract against Alzheimer's Disease.
AB  - Accumulated evidence suggests that polyphenolic antioxidants present in herbs
      play important roles in prevention of AD; the molecular mechanisms behind
      neuroprotective actions rely on the phenols through different effects on the
      amyloid-aggregation pathway. Fagopyrum dibotrys is a traditional herbal medicine
      which contains high quantity phenols. In present study, we investigate the
      beneficial pharmacological actions of Fagopyrum dibotrys extract in the APP/PS1
      transgenic mouse mode; meanwhile, effects of the FDE on the fibrillation and
      cytotoxicity of Abeta peptide were evaluated in vitro. After 9-month treatment,
      FDE exhibited multifunctional properties on Abeta-related pathologies, which
      cleaned Abeta deposits in the brain and decreased Abeta burden in the plasma,
      inhibited microhaemorrhage, and reduced reactive microglia in APP/PS1 transgenic
      mice and also promoted Abeta fibrils disaggregation and inhibited neurotoxicity
      induced by Abeta in SH-SY5Y cells. These results highlighted that FDE is an AD
      type pathology modulator with therapeutic potential against AD.

PMID- 28512498
TI  - Treatment Outcomes of Full Pulpotomy as an Alternative to Tooth Extraction in
      Molars with Hyperplastic/Irreversible Pulpitis: A Case Report.
AB  - Root canal therapy (RCT) is a common and successful treatment for irreversible
      pulpitis due to carious pulp exposure in mature permanent teeth. However, it is
      often an expensive procedure, may require multiple appointments, and requires a
      high level of training and clinical skill, specifically in molars. Uninsured
      patients, low-income patients, and patients with limited access to specialist
      care often elect for extraction of restorable teeth with irreversible pulpitis.
      There is a need for an alternative affordable treatment option to preserve their
      teeth and maintain chewing function. A case of pulpotomy using calcium-enriched
      mixture (CEM) cement in two maxillary molars (#14 and 15) in a healthy 36-year
      old patient is presented. Both teeth were diagnosed with symptomatic
      hyperplastic/irreversible pulpitis. Patient did not have dental insurance, was
      unable to afford RCT, and refused to extract the teeth. CEM pulpotomy and amalgam
      build-ups were done as an alternative to extraction. At 2-year recall, both teeth
      were functional with no signs/symptoms of inflammation/infection. Periapical
      radiographs and 3D images showed normal PDL around all roots. Pulpotomy with CEM
      biomaterial might be a viable alternative to tooth extraction for mature
      permanent teeth with hyperplastic/irreversible pulpitis, and can result in long
      term tooth retention and improved oral health.

PMID- 28512501
TI  - Effect of Traditional Chinese Medicine Product, QiangGuYin, on Bone Mineral
      Density and Bone Turnover in Chinese Postmenopausal Osteoporosis.
AB  - Introduction. The aim of this study was to investigate the efficacy of herbal
      formula QiangGuYin (QGY) in postmenopausal women. Materials and Methods. A total
      of 240 participants from six clinical centers were randomly to receive
      alendronate 70 mg/week, QGY granules 20 g/day, and placebo. Primary end points
      were BMD changes over 6 and 12 months; secondary end points were bone turnover
      markers changes at 3, 6, 9, and 12 months. Safety was monitored by clinical
      adverse events reported during the follow-up. Results. Of 240 women recruited,
      218 completed the study. Significant BMD increases from baseline were observed
      over 6 and 12 months at each observed part both in QGY and alendronate compared
      with placebo (p < 0.01). Alendronate-treated subjects had significant decreases
      in beta-CTX compared to QGY-treated subjects at each time point assessed (p <
      0.01). Reduction in t-P1NP was only observed in the QGY group at 3 and 6 months (
      23.81% and -3.07%, resp.). No significant difference was observed in the overall
      incidence of clinical adverse events among the alendronate group and the QGY
      group (5.0% versus 7.5%, p = 0.513). Conclusion. 1-Year treatment with QGY
      demonstrated a safe statistical increase in BMD and new balance may be rebuilt
      after 9 months. This trail is registered with ChiCTR-POC-16008026.

PMID- 28512500
TI  - The Effect of Chunghyul-Dan on Hyperventilation-Induced Carbon Dioxide Reactivity
      of the Middle Cerebral Artery in Normal Subjects: A Dose-Dependent Study.
AB  - Background. This study was conducted to show the prompt effect of chunghyul-dan
      (CHD) on cerebral hemodynamics in order to provide evidence for its use in stroke
      prevention. Methods. Hyperventilation-induced CO2 reactivity of the middle
      cerebral artery was measured in 12 healthy male volunteers (mean age: 26.3 +/-
      1.1 years) using transcranial Doppler sonography. All subjects were examined
      before and for 3 hours after administration, with an interval of 1 week between
      measurements. Results. Compared to baseline, the CO2 reactivity of the middle
      cerebral artery increased significantly at 2 and 3 hours after the administration
      of CHD (600 mg and 1200 mg). The mean blood pressure and heart rate did not vary
      from the baseline values in all groups. Conclusion. These data suggest that CHD
      administration (especially 600 mg) immediately improves cerebral blood flow.

PMID- 28512503
TI  - Massive Oculomotor Nerve Enlargement: A Case of Presumed Schwannomatosis.
AB  - A 45-year-old man presented with a slowly progressive pupil-involving third nerve
      palsy. Magnetic resonance imaging (MRI) revealed a tubular lesion extending from
      the interpeduncular cistern through the cavernous sinus and into the left orbit
      where it branched into a superior and an inferior division, clearly outlining the
      anatomy of the third cranial nerve. Multiple other, less pronounced, enlarged
      cranial nerves were noted. The differential diagnosis included chronic
      inflammatory demyelinating polyneuropathy (CIDP), hereditary motor and sensory
      neuropathy (HMSN), neurofibromatosis (NF), and schwannomatosis. The absence of
      other muscle weakness and of sensory symptoms combined with normal peripheral
      nerve conduction studies effectively ruled out the hypertrophic polyneuropathies
      and pointed to a syndromic cause of multiple benign peripheral nerve sheath
      tumours (PNSTs). The authors are treating this case as presumed schwannomatosis,
      a syndrome similar to NF2 with much lower frequency of acoustic neuromas.

PMID- 28512502
TI  - Health Inequalities Associated with Post-Stroke Visual Impairment in the United
      Kingdom and Ireland: A Systematic Review.
AB  - The aim of this study was to report on the health inequalities facing stroke
      survivors with visual impairments as described in the current literature. A
      systemic review of the literature was conducted to investigate the potential
      health inequalities facing stroke survivors with subsequent visual impairments. A
      quality-of-evidence and risk-of-bias assessment was conducted for each of the
      included articles using the appropriate tool dependent on the type of article.
      Only four articles discussed health inequalities affecting stroke survivors with
      visual impairment specifically. A further 23 articles identified health
      inequalities after stroke, and 38 reported on health inequalities within the
      visually impaired UK or Irish population. Stroke survivors with visual impairment
      face inconsistency in eye care provision nationally, along with variability in
      the assessment and management of visual disorders. The subgroups identified as
      most at risk were females; black ethnicity; lower socioeconomic status; older
      age; and those with lower education attainment. The issue of inconsistent service
      provision for this population must be addressed in future research. Further
      research must be conducted in order to firmly establish whether or not stroke
      survivors are at risk of the aforementioned sociodemographic and economic
      inequalities.

PMID- 28512504
TI  - A Case Report of Drug-Induced Myopathy Involving Extraocular Muscles after
      Combination Therapy with Tremelimumab and Durvalumab for Non-Small Cell Lung
      Cancer.
AB  - Recently developed anti-tumour therapies targeting immune checkpoints include
      tremelimumab and durvalumab. These agents have incompletely characterised side
      effect profiles. The authors report a 68-year-old man treated for non-small cell
      lung cancer (NSCLC) with a combination of tremelimumab and durvalumab. After
      treatment he developed diplopia, ptosis, fatigue, weakness, and an inflammatory
      myopathy affecting the extraocular muscles requiring hospitalisation.
      Electromyography (EMG) testing and muscle biopsy suggested inflammatory myopathy
      without sign of myasthenia. Within 1 month of withdrawal of cancer therapies and
      initiation of oral steroid therapy, ocular and systemic symptoms had resolved.
      This notable adverse effect has not been previously described for these drugs
      administered singly or in combination, and ophthalmologists should be aware of
      this presentation in patients treated with these agents.

PMID- 28512505
TI  - Chronic Invasive Fungal Sinusitis Presenting as Inferior Altitudinal Visual Field
      Defect.
AB  - A young male with acute blurring of vision (6/9) complained of an inferior
      altitudinal field defect in right eye. Clinical ophthalmological examination was
      normal. Magnetic resonance imaging (MRI) of the brain revealed the expansion and
      mucosal thickening of right posterior ethmoid and sphenoid sinuses and opacified
      right maxillary sinus. Surgical intervention (transethmoidal sphenoidotomy) and
      histopathological examination revealed chronic invasive granulomatous fungal
      sinusitis. Anti-fungal therapy led to resolution of visual complaints and
      restoration of visual field defects.

PMID- 28512506
TI  - Case of Primary Leptomeningeal Lymphoma Presenting with Papilloedema and
      Characteristics of Pseudotumor Syndrome.
AB  - The authors describe an immunocompetent, 50-year-old man who complained of a
      daily transient blurring of his vision with bilateral papilloedema. His visual
      acuity was 20/20 OU, and the blind spot was enlarged bilaterally. There was
      intracranial hypertension, but imaging for systemic and brain tumours were
      negative. These findings suggested a diagnosis of the pseudotumor syndrome.
      However, MRI showed leptomeningeal enhancement, and acetazolamide successfully
      resolved his visual symptoms and papilloedema. Cytology and flow cytometry of the
      CSF led to the final diagnosis of primary leptomeningeal lymphoma (PLML).
      Clinicians need to be aware that a case of PLML may be misdiagnosed as peudotumor
      cerebri.

PMID- 28512507
TI  - Homonymous Hemianopsia Due to Posterior Cortical Atrophy.
AB  - A 63-year-old woman presented to her ophthalmologist complaining of reading
      difficulties for two years. Ophthalmological examination revealed a homonymous
      hemianopsia. Brain magnetic resonance imaging (MRI) scan was interpreted as
      normal, but positron emission tomography (PET) showed areas of posterior brain
      hypometabolism. This case highlights the high diagnostic suspicion that
      ophthalmologists should have regarding posterior cortical atrophy (including the
      visual variant of Alzheimer disease) in patients complaining of reading
      difficulties in the setting of a normal ophthalmic examination.

PMID- 28512508
TI  - Lhermitte-Duclos Disease and Cerebellar Gangliocytoma-An Incidental Finding in a
      Patient with Gradual Vision Loss.
AB  - A 50-year-old male patient presented to the neuro-ophthalmology clinic with chief
      complaints of gradual decrease in vision in both eyes, more in the left eye, for
      6 years. On general examination, the patient had a hemiplegic gait. His
      presenting acuity was 20/50 in the right eye and 20/320 in the left eye, not
      improving further. He had dense posterior subcapsular cataracts in both eyes, and
      fundus examination revealed pale discs. Humphrey visual field tests 30-2 revealed
      a vertical nasal midline defect in the right eye and grossly depressed fields in
      the left eye. Keeping in mind the above findings, the authors requested for a
      magnetic resonance imaging (MRI) of the brain. The brain MRI shows a large
      infarct in the right parieto-occipital lobe and a small circumscribed lesion in
      the left cerebellum. The radiologist opined that it could possibly be a
      gangliocytoma of the cerebellum, and a possible diagnosis of Lhermitte-Duclos
      syndrome was made.

PMID- 28512510
TI  - Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive
      External Ophthalmoplegia.

PMID- 28512509
TI  - United Kingdom CSF Disorders Day, 14th October 2016, University Hospitals
      Birmingham.
AB  - The management of patients with cerebrospinal fluid (CSF) disorders requires a
      multi-specialty approach involving specialists in neurosurgery, neurology,
      neuroradiology, and neuro-ophthalmology. A symposium on CSF disorders took place
      at University Hospitals Birmingham and covered a selection of the more
      challenging and controversial issues facing the multi-specialty team. The meeting
      also featured a synopsis of the latest scientific research. The authors provide
      an overview of the event.

PMID- 28512511
TI  - Automated Detection of Red Lesions Using Superpixel Multichannel Multifeature.
AB  - Red lesions can be regarded as one of the earliest lesions in diabetic
      retinopathy (DR) and automatic detection of red lesions plays a critical role in
      diabetic retinopathy diagnosis. In this paper, a novel superpixel Multichannel
      Multifeature (MCMF) classification approach is proposed for red lesion detection.
      In this paper, firstly, a new candidate extraction method based on superpixel is
      proposed. Then, these candidates are characterized by multichannel features, as
      well as the contextual feature. Next, FDA classifier is introduced to classify
      the red lesions among the candidates. Finally, a postprocessing technique based
      on multiscale blood vessels detection is modified for removing nonlesions
      appearing as red. Experiments on publicly available DiaretDB1 database are
      conducted to verify the effectiveness of our proposed method.

PMID- 28512512
TI  - Learning about Chemiosmosis and ATP Synthesis with Animations Outside of the
      Classroom.
AB  - Many undergraduate biology courses have begun to implement instructional
      strategies aimed at increasing student interaction with course material outside
      of the classroom. Two examples of such practices are introducing students to
      concepts as preparation prior to instruction, and as conceptual reinforcement
      after the instructional period. Using a three-group design, we investigate the
      impact of an animation developed as part of the Virtual Cell Animation Collection
      on the topic of concentration gradients and their role in the actions of ATP
      synthase as a means of pre-class preparation or post-class reinforcement compared
      with a no-intervention control group. Results from seven sections of introductory
      biology (n = 732) randomized to treatments over two semesters show that students
      who viewed animation as preparation (d = 0.44, p < 0.001) or as reinforcement (d
      = 0.53, p < 0.001) both outperformed students in the control group on a follow-up
      assessment. Direct comparison of the preparation and reinforcement treatments
      shows no significant difference in student outcomes between the two treatment
      groups (p = 0.87). Results suggest that while student interaction with animations
      on the topic of concentration gradients outside of the classroom may lead to
      greater learning outcomes than the control group, in the traditional lecture
      based course the timing of such interactions may not be as important.

PMID- 28512513
TI  - Using a Concept Inventory to Reveal Student Thinking Associated with Common
      Misconceptions about Antibiotic Resistance.
AB  - Misconceptions, also known as alternate conceptions, about key concepts often
      hinder the ability of students to learn new knowledge. Concept inventories (CIs)
      are designed to assess students' understanding of key concepts, especially those
      prone to misconceptions. Two-tiered CIs include prompts that ask students to
      explain the logic behind their answer choice. Such two-tiered CIs afford an
      opportunity for faculty to explore the student thinking behind the common
      misconceptions represented by their choice of a distractor. In this study, we
      specifically sought to probe the misconceptions that students hold prior to
      beginning an introductory microbiology course (i.e., preconceptions). Faculty
      learning communities at two research-intensive universities used the validated
      Host-Pathogen Interaction Concept Inventory (HPI-CI) to reveal student
      preconceptions. Our method of deep analysis involved communal review and
      discussion of students' explanations for their CI answer choice. This approach
      provided insight valuable for curriculum development. Here the process is
      illustrated using one question from the HPI-CI related to the important topic of
      antibiotic resistance. The frequencies with which students chose particular
      multiple-choice responses for this question were highly correlated between
      institutions, implying common underlying misconceptions. Examination of student
      explanations using our analysis approach, coupled with group discussions within
      and between institutions, revealed patterns in student thinking to the
      participating faculty. Similar application of a two-tiered concept inventory by
      general microbiology instructors, either individually or in groups, at other
      institutions will allow them to better understand student thinking related to key
      concepts in their curriculum.

PMID- 28512514
TI  - First-Year and Non-First-Year Student Expectations Regarding In-Class and Out-of
      Class Learning Activities in Introductory Biology.
AB  - National calls for teaching transformation build on a constructivist learning
      theory and propose that students learn by actively engaging in course activities
      and interacting with other students. While interactive pedagogies can improve
      learning, they also have the potential to challenge traditional norms regarding
      class participation and learning strategies. To better understand the potential
      openness of students to interactive teaching practices, we administered a survey
      during the first week of two sections of an introductory biology course to
      characterize how students envisioned spending time during class as well as what
      activities they expected to complete outside of class during non-exam weeks and
      in preparation for exams. Additionally, we sought to test the hypothesis that the
      expectations of first-year students differed from those of non-first-year
      students. Analyses of closed-ended and open-ended questions revealed that
      students held a wide range of expectations and that most students expressed
      expectations consistent with some degree of transformed teaching. Furthermore,
      first-year students expected more active learning in class, more out-of-class
      coursework during non-exam weeks, and more social learning strategies than non
      first-year students. We discuss how instructor awareness of incoming student
      expectations might be used to promote success in introductory science courses.

PMID- 28512515
TI  - Biofilms for Babies: Introducing Microbes and Biofilms to Preschool-Aged
      Children.

PMID- 28512516
TI  - A Simple Activity to Enhance the Learning Experience of Reading Primary
      Literature.

PMID- 28512518
TI  - Development of Oral Communication Skills by Undergraduates that Convey
      Evolutionary Concepts to the Public.

PMID- 28512519
TI  - An Internship May Not Be Enough: Enhancing Bioscience Industry Job Readiness
      through Practicum Experiences.
AB  - In contrast to the narrowing of options in academic careers, the bioscience
      industry offers robust employment opportunities for STEM-trained workers,
      especially those who display both scientific and business talent. Unfortunately,
      traditional science programs typically lack curricular features that develop this
      type of worker. The North Carolina State University Master of Microbial
      Biotechnology (MMB) program facilitates industry-specific experiential learning
      to fill this training gap. Similar programs often rely on a single industry
      internship to provide students relevant work experience, but completion of one
      internship might not suffice to position students for employment in a highly
      competitive job market. The MMB program requires students to complete an
      internship and three practicum projects in an industry setting, to promote
      development of key skills in a variety of areas, to build confidence in the
      ability to perform initial job duties, and to establish a more extensive work
      history in industry. In this Perspective we discuss an unmet need in
      undergraduate and graduate STEM education that can be filled by incorporating a
      similar set of industry-specific work experiences for students who desire to
      transition from academe into the life science industry.

PMID- 28512517
TI  - siRNA Immunological Fishing Training (SIFT) Experience as a Novel Research
      Education Tool for Students Studying Immunology.

PMID- 28512521
TI  - Using Pre-Assessment and In-Class Questions to Change Student Understanding of
      Molecular Movements.
AB  - Understanding how different types of molecules move through cell membranes is a
      fundamental part of cell biology. To identify and address student misconceptions
      surrounding molecular movement through cell membranes, we surveyed student
      understanding on this topic using pre-class questions, in-class clicker
      questions, and subsequent exam questions in a large introductory biology course.
      Common misconceptions identified in student responses to the pre-class assessment
      questions were used to generate distractors for clicker questions. Two-tier
      diagnostic clicker questions were used to probe incoming common student
      misconceptions (first tier) and their reasoning (second tier). Two subsequent
      lectures with assessment clicker questions were used to help students construct a
      new framework to understand molecular movement through cell membranes. Comparison
      of pre-assessment and post-assessment (exam) performance showed dramatic
      improvement in students' understanding of molecular movement: student answers to
      exam questions were 74.6% correct with correct reasoning while only 1.3% of the
      student answers were correct with correct reasoning on the pre-class assessment.
      Our results show that students' conceptual understanding of molecular movement
      through cell membranes progressively increases through discussions of a series of
      clicker questions and suggest that this clicker-based teaching strategy was
      highly effective in correcting common student misconceptions on this topic.

PMID- 28512522
TI  - Photo Animation Brings Scientists Back to Life in the Classroom.

PMID- 28512523
TI  - Student Buy-In Toward Formative Assessments: The Influence of Student Factors and
      Importance for Course Success.
AB  - Formative assessment (FA) techniques, such as pre-class assignments, in-class
      activities, and post-class homework, have been shown to improve student learning.
      While many students find these techniques beneficial, some students may not
      understand how they support learning or may resist their implementation.
      Improving our understanding of FA buy-in has important implications, since buy-in
      can potentially affect whether students fully engage with and learn from FAs. We
      investigated FAs in 12 undergraduate biology courses to understand which student
      characteristics influenced buy-in toward FAs and whether FA buy-in predicted
      course success. We administered a mid-semester survey that probed student
      perceptions toward several different FA types, including activities occurring
      before, during, and after class. The survey included closed-ended questions
      aligned with a theoretical framework outlining key FA objectives. We used factor
      analysis to calculate an overall buy-in score for each student and general linear
      models to determine whether certain characteristics were associated with buy-in
      and whether buy-in predicted exam scores and course grades. We found that unfixed
      student qualities, such as perceptions, behaviors, and beliefs, consistently
      predicted FA buy-in, while fixed characteristics, including demographics,
      previous experiences, and incoming performance metrics, had more limited effects.
      Importantly, we found that higher buy-in toward most FA types predicted higher
      exam scores and course grades, even when controlling for demographic
      characteristics and previous academic performance. We further discuss steps that
      instructors can take to maximize student buy-in toward FAs.

PMID- 28512524
TI  - Promoting the Multidimensional Character of Scientific Reasoning.
AB  - This study reports part of a long-term program to help students improve
      scientific reasoning using higher-order cognitive tasks set in the discipline of
      cell biology. This skill was assessed using problems requiring the construction
      of valid conclusions drawn from authentic research data. We report here efforts
      to confirm the hypothesis that data interpretation is a complex, multifaceted
      exercise. Confirmation was obtained using a statistical treatment showing that
      various such problems rank students differently-each contains a unique set of
      cognitive challenges. Additional analyses of performance results have allowed us
      to demonstrate that individuals differ in their capacity to navigate five
      independent generic elements that constitute successful data interpretation:
      biological context, connection to course concepts, experimental protocols, data
      inference, and integration of isolated experimental observations into a coherent
      model. We offer these aspects of scientific thinking as a "data analysis skills
      inventory," along with usable sample problems that illustrate each element.
      Additionally, we show that this kind of reasoning is rigorous in that it is
      difficult for most novice students, who are unable to intuitively implement
      strategies for improving these skills. Instructors armed with knowledge of the
      specific challenges presented by different types of problems can provide specific
      helpful feedback during formative practice. The use of this instructional model
      is most likely to require changes in traditional classroom instruction.

PMID- 28512526
TI  - The Founding of a Journal.

PMID- 28512527
TI  - The Future of CaJEM.

PMID- 28512525
TI  - H2S Donor NaHS Changes the Production of Endogenous H2S and NO in D-Galactose
      Induced Accelerated Ageing.
AB  - Aims. The study was designed to explore whether hydrogen sulphide (H2S) and
      nitric oxide (NO) generation changed in D-galactose- (D-gal-) induced ageing, the
      possible effects of exogenous H2S supplementation, and related mechanisms.
      Results. In D-gal-induced senescent mice, both H2S and NO levels in the heart,
      liver, and kidney tissues were decreased significantly. A similar trend was
      observed in D-gal-challenged human umbilical vein endothelial cells (HUVECs).
      Sustained H2S donor (NaHS) treatment for 2 months elevated H2S and NO levels in
      these mice, and during this period, the D-gal-induced senescent phenotype was
      reversed. The protective effect of NaHS is associated with a decrease in reactive
      oxygen species levels and an increase in antioxidants, such as glutathione, and
      superoxide dismutase and glutathione peroxidase activities. Increased expression
      of the H2S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine
      beta-synthase (CBS) in the heart, liver, and kidney tissues was observed in the
      NaHS-treated groups. NaHS supplementation also significantly postponed D-gal
      induced HUVEC senescence. Conclusions. Endogenous hydrogen sulphide production in
      both ageing mice and endothelial cells is insufficient. Exogenous H2S can
      partially rescue ageing-related dysfunction by inducing endogenous H2S and NO
      production and reducing oxidative stress. Restoring endogenous H2S production may
      contribute to healthy ageing, and H2S may have antiageing effects.

PMID- 28512528
TI  - Introducing the New Editor-In-Chief.

PMID- 28512529
TI  - From the Cal/AAEM representative on the CAL/ACEP Governmental Affairs Committee.

PMID- 28512530
TI  - Resident/Student Corner.

PMID- 28512531
TI  - Pro Position for Filming in The ED.

PMID- 28512533
TI  - Rebuttal to "Saying No..."

PMID- 28512532
TI  - Saying No to Cameras in the Emergency Department.

PMID- 28512534
TI  - Rebuttal to "Pro Filming in the ED".

PMID- 28512535
TI  - Evaluation of surface roughness of enamel after various bonding and clean-up
      procedures on enamel bonded with three different bonding agents: An in-vitro
      study.
AB  - BACKGROUND: The purpose of this study was to analyze and compare the enamel
      surface roughness before bonding and after debonding, to find correlation between
      the adhesive remnant index and its effect on enamel surface roughness and to
      evaluate which clean-up method is most efficient to provide a smoother enamel
      surface. MATERIAL AND METHODS: 135 premolars were divided into 3 groups
      containing 45 premolars in each group. Group I was bonded by using moisture
      insensitive primer, Group II by using conventional orthodontic adhesive and Group
      III by using self-etching primer. Each group was divided into 3 sub-groups on the
      basis of type of clean-up method applied i,e scaling followed by polishing,
      tungsten carbide bur and Sof-Lex disc. Enamel surface roughness was measured and
      compared before bonding and after clean-up. RESULTS: Evaluation of pre bonding
      and post clean-up enamel surface roughness (Ra value) with the t test showed that
      Post clean-up Ra values were greater than Pre bonding Ra values in all the groups
      except in teeth bonded with self-etching primer cleaned with Sof-Lex disc.
      Reliability of ARI score taken at different time interval tested with Kruskal
      Wallis test suggested that all the readings were reliable. CONCLUSIONS: No clean
      up procedure was able to restore the enamel to its original smoothness. Self
      etching primer and Sof-Lex disc clean-up method combination restored the enamel
      surface roughness (Ra value) closest to its pre-treatment value. Key words:Enamel
      surface roughness, clean-up method, adhesive remnant index.

PMID- 28512536
TI  - Effect of Smear Clear and Some Other Commonly Used Irrigants on dislodgement
      resistance of Mineral Trioxide Aggregate to Root Dentin.
AB  - BACKGROUND: This study aimed to assess the push-out bond strength of mineral
      trioxide aggregate (MTA) to root canal dentin after irrigation with Smear Clear
      in comparison with 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) and
      saline as commonly used root canal irrigants. MATERIAL AND METHODS: The coronal
      and mid-root areas of maxillary anterior teeth were horizontally sectioned into
      one-millimeter thick slices. The root canal lumen of dentinal slices was dilated
      using a diamond bur with 1.3 mm diameter. After the application of MTA, the
      samples were incubated in 100% humidity for 10 minutes and were then randomly
      divided into four groups (n=20) and immersed in Smear Clear, 2.5% NaOCl, 2% CHX
      and saline for 30 minutes. No irrigant was used for the control group (n=20). A
      wet cotton pellet was placed on the samples and after 48 hours of incubation,
      push-out bond strength was measured using a universal testing machine. The
      samples were evaluated under a stereomicroscope to determine the mode of failure.
      One-way ANOVA was used to assess statistical differences among the groups.
      RESULTS: The control group showed the highest bond strength with significant
      differences with other groups (P<0.05). Among the experimental groups, the saline
      group had no significant difference with CHX (P=0.09) but it had significant
      differences with Smear Clear and NaOCl groups (P<0.05). No significant difference
      in bond strength to MTA was noted after irrigation with Smear Clear, CHX and
      NaOCl (P>0.05). Other pairwise comparisons showed no significant difference
      (P>0.05). CONCLUSIONS: Irrigation with Smear Clear, CHX and NaOCl did not cause a
      significant change in bond strength of MTA to dentin. Key words:Root Canal
      Irrigants, push-out, Mineral Trioxide Aggregate, dentin.

PMID- 28512537
TI  - Decreased dentin tubules density and reduced thickness of peritubular dentin in
      hyperbilirubinemia-related green teeth.
AB  - BACKGROUND: It is stated anecdotally that patients with liver diseases in
      childhood who develop green teeth have increased risk for rampant caries, which
      may be secondary to changes in dental structure. The aim of this study was to
      test the hypothesis that hyperbilirubinemia affects the dentin morphology of
      green teeth. MATERIAL AND METHODS: Sixteen primary teeth were prepared and
      divided into two groups (green teeth, n = 8 and control, n = 8), which were
      transversely fractured across the cervical third of the dental crowns; dentin was
      prepared and sputter-coated with gold, and examined under a scanning electron
      microscope. The mean density and mean diameter of dentin tubules, as well as the
      thickness of peritubular dentin, were compared. RESULTS: Hyperbilirubinemia was
      associated with a decrease in the density of the dentin tubules (p< .01) and the
      thickness of peritubular dentin of green teeth (p< .01). CONCLUSIONS: There was a
      correlation between childhood hyperbilirubinemia and changes in the dentin
      morphology, including a decrease in the density of the dentin tubules and a
      reduction in the thickness of peritubular dentin in green teeth. Key
      words:Hyperbilirubinemia, liver disease, childhood, dentin tubules, human teeth,
      scanning electron microscopy.

PMID- 28512538
TI  - Oral hygiene and periodontal health status among khat chewers. A case-control
      study.
AB  - BACKGROUND: Habitual khat chewing is a widespread male habit in Southern Arabia
      and East Africa. The aim of this study was to assess the effect of Khat chewing
      on oral hygiene and periodontal health status among Yemeni male khat chewers.
      MATERIAL AND METHODS: This case- control study included 310 khat chewers, aged 20
      65 years, and 72 age- and gender- matched non-chewers as controls. Periodontal
      examination included recording of dental plaque index (PI), gingival index (GI),
      probing pocket depth (PPD), attachment level (AL) and gingival recession (GR).
      Demographic data, oral hygiene practices, and duration, frequency and site of
      khat chewing were obtained using questionnaires. SPSS was used for data analysis.
      ANOVA and t- tests were used to compare groups. RESULTS: Khat chewers had
      significantly higher mean PI, AL, GR scores than non-chewers (P < 0.05). However,
      no significant differences in the GI and PPD mean scores were observed between
      both groups (p > 0.05). Interestingly, the results showed that the chewing side
      had less PI, GI and PPD than non-chewing side. However, gingival recession was
      significantly higher in the chewing side. The duration of chewing showed a
      significant effect on PI, PPD, AL, and GR but had no effect on the gingival
      condition. Likewise, the frequency of chewing showed a significant effect on PPD,
      AL, and GR, but had no effect on other indices (PI and GI). CONCLUSIONS: The
      results of this study indicate that khat chewing have a detrimental effect on the
      periodontium. Key words:Khat chewing, periodontal health, oral hygiene.

PMID- 28512539
TI  - Longitudinal effects of rapid maxillary expansion on masticatory muscles
      activity.
AB  - BACKGROUND: To investigate the modifications induced by rapid maxillary expansion
      (RME) on the electromyographic (EMG) activities of the anterior temporal and
      superficial masseter muscles, in patients without pre-treatment EMG alterations.
      MATERIAL AND METHODS: Twenty-one patients with unilateral posterior cross-bite
      selected from the orthodontic department of the University of L'Aquila (Italy),
      were enrolled. There was no control group in this study since each subject acted
      as a control of her/himself. Two surface EMG recordings were taken: T0 (before
      RME) and at T1 (3 month after the end of expansion). To verify the neuromuscular
      equilibrium, the EMG activities of both right and left masseter and anterior
      temporal muscles were recorded during a test of maximum clench. EMG indexes were
      compared by paired Student's t-test. RESULTS: In both occasions, all indices
      showed a good symmetry between the right and left side masticatory muscles. No
      statistically significant differences were found between the two recordings.
      CONCLUSIONS: In children without pre-treatment EMG alterations, no variations in
      standardized muscular activity after RME were found. The treatment did not alter
      the equilibrium of the masseter and temporal muscles. Key words:Rapid maxillary
      expansion, electromyography, masticatory muscles.

PMID- 28512540
TI  - The effects of three remineralizing agents on regression of white spot lesions in
      children: A two-week, single-blind, randomized clinical trial.
AB  - BACKGROUND: This study investigated the effect of three remineralizing agents on
      improving white spot lesions (WSLs). MATERIAL AND METHODS: This clinical trial
      included children who had at least one WSL on anterior teeth of upper or lower
      jaws. The participants were randomly assigned to 4 groups by treatment: 1) a
      cream containing casein phosphopeptide-amorphous calcium phosphate and fluoride
      (MI Paste Plus); 2) a cream containing hydroxyapatite and fluoride (Remin Pro);
      3) a 2% sodium fluoride gel; and 4) usual home care (control). The treatment was
      performed for 3 times over 10 days using special trays for retaining
      remineralizing agents. The area and mineral content of WSLs were measured at
      baseline (T1) and 1 day after finishing treatment (T2). Blinding was applied for
      outcome assessment. RESULTS: Eighty patients were assigned to MI Paste Plus,
      Remin Pro, NaF or control groups. The application of all remineralizing agents
      caused a significant decrease in area and a significant increase in mineral
      content of WSLs (p<0.05), whereas the control patients did not experience any
      significant alteration (p>0.05). At T2, the area of WSLs was significantly lower
      in three experimental groups compared to the control group (p=0.023), but between
      group difference in mineral content of WSLs failed to achieve statistical
      significance (p=0.08). CONCLUSIONS: The in-office application of either MI Paste
      Plus or Remin Pro was as effective as 2% NaF for reducing area and increasing
      mineral content of WSLs. MI Paste Plus and Remin Pro could be recommended as
      suitable alternatives to NaF for managing WSLs. Key words:White spot lesion,
      caries, casein phosphopeptide-amorphous calcium phosphate, hydroxyapatite, sodium
      fluoride, CPP-ACP, MPlus, Remin Pro, NaF.

PMID- 28512541
TI  - Anti-plaque and anti-gingivitis effect of Papain, Bromelain, Miswak and Neem
      containing dentifrice: A randomized controlled trial.
AB  - BACKGROUND: Patients undergoing fixed orthodontic therapy may have difficulty in
      maintaining a good oral hygiene due to the difficulty posed by the appliances in
      accessing such areas. This study aimed to compare anti-plaque and anti-gingivitis
      efficacy of dentifrice containing Papain, Bromelain, Miswak and Neem with a
      standard dentifrice among patient's undergoing fixed orthodontic treatment.
      MATERIAL AND METHODS: Single center, single blind, parallel arm, randomized
      controlled clinical trial with an allocation ratio of 1:1 was conducted.
      Evaluation of plaque and gingivitis was done using Williams modification of
      Silness and Loe Plaque Index (PI) for use in orthodontic subjects and Loe and
      Silness's Gingival Index (GI) at baseline and one month. RESULTS: Inter-group
      comparison showed there was significantly lower mean plaque index in test (0.88
      +/-0.05) than in control group (1.17 +/-0.05) after adjusting for the baseline
      plaque index (p<0.001). Similarly, there was significantly lower mean gingival
      index in test (0.87 +/-0.04) than in control group (1.14 +/-0.04) after adjusting
      for the baseline gingival index (p<0.001). CONCLUSIONS: The efficacy of the test
      dentifrice in limiting plaque and gingivitis suggests that it can be used as a
      home based adjunct to clinical therapy in orthodontic patients. Key
      words:Bromelain, gingivitis, miswak, neem, papain, plaque.

PMID- 28512542
TI  - Cambra system in patients awaiting hematopoietic progenitor cell transplant and
      high caries risk.
AB  - BACKGROUND: Recent times have witnessed a significant increase in the number of
      patients affected by problems related to oncological treatment Aims of this study
      is to evaluate dental affectation among patients awaiting hematopoietic
      progenitor cell transplant (HPCT), and they showed high caries risk, so it should
      establish a protocol prior to transplantation. MATERIAL AND METHODS: The study
      included 72 patients due for HPCT. Clinical and radiological explorations were
      performed and oral photos taken. The amount of caries, missing teeth and fillings
      were registered for each patient. CAO, DMFS and Restoration Indices were
      calculated. RESULTS: 83% of patients presented caries. 48 patients (67%) had lost
      at least one tooth. Only 32 patients (44%) had received some sort of conservative
      treatment. The average CAO index value obtained was 10.37. The DMFS index showed
      an average of 27.06 affected surfaces. Of the 72 patients studied, 40 (56%)
      showed a restoration index value of zero. CONCLUSIONS: These patients presented a
      high number of carious teeth and a low restoration index. The presence of so many
      possible septic foci in an individual, who will later become susceptible to
      infection, highlights the importance of preventative treatment and bucco-dental
      restoration within this patient population. These patients with a high caries
      risk can be treated with CAMBRA system. Key words:Hematopoietic progenitor cell
      transplantation, high caries risk, state of oral health, haematological disease,
      CAMBRA system.

PMID- 28512543
TI  - Tensile strength and impact strength of color modified acrylic resin reinforced
      with titanium dioxide nanoparticles.
AB  - BACKGROUND: Poor mechanical properties are among the main limitations of acrylic
      resins. Addition of titanium dioxide (TiO2) nanoparticles to acrylic resin has
      been shown to improve its mechanical properties with an adverse effect on its
      color. Thus, this study sought to assess the tensile and impact strength of a
      color modified heat cure acrylic resin reinforced with TiO2 nanoparticles.
      MATERIAL AND METHODS: In this in vitroexperimental study, 1wt% TiO2 nanoparticles
      were added to SR Triplex Hot heat-cure acrylic resin powder and mixed. Pigments
      and color fibers were also added and 18 samples were fabricated of this paste for
      tensile and impact strength testing (n=9) according to ISO5271. Eighteen control
      samples were also fabricated from the acrylic powder without any modification.
      Independent t-test was used for data analysis (P< 0.05). RESULTS: The mean
      tensile strength of the reinforced group was found to be significantly higher
      (difference of 11 MPa) than that of the control group (P=0.001). The mean impact
      strength of the reinforced group was 7 MPa higher than that of the control group
      and this difference was statistically significant as well (P=0.001). CONCLUSIONS:
      The color modified acrylic resin reinforced with 1wt% TiO2 showed significantly
      higher tensile and impact strength compared to the conventional acrylic resin.
      Thus, TiO2 nanoparticles may be incorporated into color-modified acrylic resin
      powder to enhance its tensile and impact strength, given that they have no
      adverse effect on other properties. Key words:Tensile strength, acrylic resins,
      titanium dioxide, impact strength.

PMID- 28512544
TI  - Oral health related quality-of-life outcomes of partially edentulous patients
      treated with implant-supported single crowns or fixed partial dentures.
AB  - BACKGROUND: Oral health-related quality of life (OHRQoL) is afflicted by
      different variables. Limited information is available regarding the impact of
      different phases of implant therapy on OHRQoL of edentulous patients. This study
      was carried out to assess the OHRQoL of patients treated with implant-supported
      single crowns or fixed partial dentures. MATERIAL AND METHODS: A total of 79
      healthy partially edentulous subjects needing implant therapy were incorporated
      in this study. Before placement of the implants, the subjects were instructed to
      fill the original version of OHIP questionnaire. Subsequently patients received
      titanium oral implants of the ITI(r) Dental Implant System. After 1st, 2nd and
      3rd year of implant placement, patients filled the same OHIP-49 questionnaire. In
      this manner the impact of implant therapy on OHRQoL by putting in comparison pre-
      and post-treatment OHIP-49 scores was assessed. Statistical analyses were
      performed using Statistical Package for the Social Science software (SPSS,
      version 22, Chicago, IL, USA). Paired t test and Unpaired t test were performed
      and a statistical significance was set at 5% level of significance (p<0.05).
      RESULTS: Functional limitation, physical pain, psychological discomfort, physical
      disability, psychological disability, social disability were significantly
      decreased from baseline to 1st year (p<0.05) except handicap (p>0.05). All
      variables were also significantly decreased from baseline to 2nd year and 3rd
      year (p<0.05). There were no significant differences dependent on gender with
      respect to OHIP (p>0.05). Patients aged less than 60 years and more than 60 years
      of age groups differed significantly with respect to OHIP scores measured at 1st
      year, 2nd year and at 3rd year of implant placement (p<0.05). CONCLUSIONS:
      Decrease in pre- and post-treatment OHIP scores OHIP demonstrated the significant
      increase in the OHRQoL after the therapy, which suggested increased levels of
      patient satisfaction. Key words:Edentulism, dental implants, Oral health-related
      quality-of-life.

PMID- 28512545
TI  - Effect of hemostatic agent on marginal gaps of class V giomer restorations.
AB  - BACKGROUND: Contamination of dentin with hemostatic agents might exert a
      deleterious effect on adhesive procedures on dentin. The present study was
      undertaken to investigate the effect of aluminum chloride hemostatic agent on
      marginal gaps in Cl V giomer restorations. MATERIAL AND METHODS: Fifty sound
      bovine permanent incisors were selected for the purpose of this in vitro study
      and Cl V cavities were prepared on their buccal surfaces; the gingival margins of
      the cavities were placed in dentin. The tooth samples were randomly assigned to
      two groups (n=25). The samples in groups 1 and 2 underwent a restorative
      procedure without and with the application of aluminum chloride hemostatic agent
      in the cavity, respectively, before application of the adhesive. BeautiBond one
      step self-etch adhesive and Beautifil II giomer restorative material were used
      for the restoration of the cavities in both groups. The samples were thermocycled
      and sectioned, followed by measuring the gap sizes at gingival margins in um
      under a stereomicroscope. The marginal gaps were compared with Mann-Whitney U
      test. Statistical significance was set at P<0.05. RESULTS: The results showed
      significant differences in the mean marginal gaps between the two groups under
      study (P<0.001); the mean marginal gaps were higher in group 2 (with hemostatic
      agent) compared to those in group 1 (without hemostatic agent) (P<0.0005).
      CONCLUSIONS: Contamination with aluminum chloride hemostatic agent in giomer
      restorations gave rise to higher gingival margin gaps. Key words:Dental
      adhesives, giomer restorative material, hemostatic agent, marginal adaptation.

PMID- 28512547
TI  - Vascular labeling of the head and neck vessels: Technique, advantages and
      limitations.
AB  - BACKGROUND: Vascular staining techniques have been used to describe the vascular
      structures of several anatomic areas. However, few reports have described this
      procedure in the head and neck region. This paper describes a head and neck
      vascular labeling procedure, and describes some of the technical complications
      that may occur. MATERIAL AND METHODS: Fifteen specimen cadaver heads were
      prepared. After drying the vascular system, the internal carotid arteries were
      ligated and a solution with latex and a gelling agent was injected into the
      internal carotid arteries and external jugular veins. Two different colors were
      employed to differentiate arteries from veins. A total of 60ml latex was injected
      into each blood vessel. Subsequently, the specimens were refrigerated at 5
      degrees C for a minimum of 24 hours. Finally, a dissection was performed to
      identify the venous and arterial systems of the maxillofacial region. RESULTS: In
      most specimens, correct identification of the vascular structures (lingual
      artery, pterigoyd plexus, and the major palatal arteries, among others) was
      possible. However, in three heads a major technical problem occurred (the latex
      remained liquid), making the dissection unfeasible. Other minor complications
      such as latex obstruction due to the presence of atheromas were found in two
      further specimens. CONCLUSIONS: The vascular labeling technique is a predictable,
      effective and simple method for analyzing the vascular system of the
      maxillofacial area in cadaveric studies, including vessels of reduced diameter or
      with an intraosseous course. This procedure can be especially useful to teach
      vascular anatomy to dental students and postgraduate residents. Key words:Blood
      vessels, vascular casting, vascular labeling, head and neck arteries, carotid
      arteries, jugular veins.

PMID- 28512546
TI  - Evaluation of the effect of different enamel surface treatments and waiting times
      on the staining prevention after bleaching.
AB  - BACKGROUND: Bleached dental enamel can be more susceptible to staining than the
      enamel that has never been bleached, especially right after tooth bleaching. The
      aim of this study is to evaluate the effect of surface treatments and waiting
      time prior to contact with dye on bleached enamel staining susceptibility.
      MATERIAL AND METHODS: One hundred teeth were bleached with 35% hydrogen peroxide
      (Whiteness HP, FGM) and randomly assigned to G1 artificial saliva, G2 2% sodium
      fluoride (Flugel, Nova DFL), G3 casein phosphopeptide-amorphous calcium phosphate
      fluoride paste (CPP-ACPF, MI Paste Plus, GC America), G4 rinse for color
      maintenance after bleaching (Keep White Rinse, DMC) and G5 polishing with
      aluminum oxide-impregnated disks (Super Buff Disk, Shofu). Fifty specimens were
      immersed in red wine for 15 minutes, immediately after treatment, and the others
      one hour after. Color difference (?E) was evaluated with a spectrophotometer
      (Vita EasyShade). Surface treatments and waiting time effects were analyzed with
      Kruskal-Wallis and Mann Whitney tests (p<0.05). RESULTS: Surface treatments
      (p>0.05) and waiting time (p>0.05) were not significant to decrease bleached
      enamel susceptibility to red wine staining. CONCLUSIONS: Surface treatments were
      similar to artificial saliva for bleached enamel susceptibility to red wine
      staining. Immediate or one-hour-postponed contact with red wine did not affect
      bleached enamel color. Key words:Tooth bleaching, color, dental enamel, hydrogen
      peroxide, pigmentation.

PMID- 28512548
TI  - Relationship between pulp-tooth volume ratios and chronological age in different
      anterior teeth on CBCT.
AB  - BACKGROUND: The CBCT imaging technique exhibits proper accuracy to determine the
      internal anatomy of teeth. Therefore, this technique can use to estimate age by
      measuring the amount of decrease in the volume of the pulpal cavity of teeth. The
      aim of the present study was to evaluate the correlation between chronological
      age and pulp-to-tooth volume ratios in anterior teeth with the use of the CBCT
      technique and to determine a regression model to estimate human age. MATERIAL AND
      METHODS: In this present descriptive-analytical study, 122 subjects (46 males and
      76 females), with an age range of 13-70 years, were evaluated. The MIMICS
      software program was used to determine the pulp-to-tooth volume ratios in 732
      anterior teeth. Regression analysis was used to assess the correlation between
      age and pulp to tooth volume ratios. RESULTS: In all the teeth evaluated, there
      was an inverse and significant correlation between age and the pulp-to-tooth
      volume ratios in males and females, with a stronger correlation in males. In
      addition, such a correlation was stronger in maxillary central incisors and
      canines. In the model in which the mean of ratios in anterior teeth was used to
      estimate age the correlation was stronger compared to that in single tooth.
      CONCLUSIONS: In general, the results of the present study showed that it is
      advisable to use the mean of all the ratios of anterior teeth in forensics to
      estimate age. Key words:Age estimation , cone-beam CT, forensic dentistry,
      secondary dentin, pulp cavity.

PMID- 28512549
TI  - Evaluation of the effectiveness of the photobiomodulation in the treatment of
      dentin hypersensitivity after basic therapy. A randomized clinical trial.
AB  - BACKGROUND: Dentin hypersensitivity (DH) in one of the most common causes of
      patient discomfort in the general population and its prevalence is higher in
      patients who have received basic or surgical periodontal treatment. Efficiency of
      the diode laser with different wavelengths has been studied by several authors,
      showing an improvement rate of the DH between 60-98%. The aim of the present
      study was to evaluate the effect of photobiomodulation (PBM) treatment on the
      reduction of DH after non surgical periodontal treatment. MATERIAL AND METHODS: A
      randomized split mouth clinical trial was performed involving 30 patients (120
      teeth) diagnosed with DH after scaling and root planning. Two teeth of the
      experimental side were treated with the laser and 2 teeth of the control side
      were treated without activating the laser. The laser treatment parameters for
      each tooth were 660nm, 200mW, CW, illuminated area 1.15cm2, 173mW/cm2, 60
      seconds, 12 J, 10.4J/cm2. Age, gender, smoking, plaque index, gingival recession,
      probing and VAS (for tactile and thermal stimulation) were registered before the
      laser treatment, immediate post treatment (after 2 minutes), 2 weeks, 1 month and
      2 months after treatment. RESULTS: There was significant difference (p<0.01) in
      discomfort to thermal and mechanical stimulation between the control and diode
      laser treatment sites at all evaluation periods. The level of discomfort
      decreased immediately following diode laser therapy, and continued to demonstrate
      a decrease for the duration of the study. All teeth remained vital after laser
      treatment, without adverse reactions or complications. CONCLUSIONS: The PBM can
      be used to reduce DH without detrimental pulpal effects. Key words:Dental
      hypersensitivity, laser, diode laser, photobiomodulation.

PMID- 28512550
TI  - Analysis of scientific production in spanish implantology.
AB  - BACKGROUND: The aim of the study was to quantify the scientific productivity of
      researchers, organizations, and regions in Spain that publish articles on
      implantology in dental journals indexed in Journal Citation Reports. MATERIAL AND
      METHODS: A search was conducted among the core collection of Thomson Reuters' Web
      of Science database, on the basis of its broad thematic and geographic coverage
      of health sciences. The search identified original articles - the main vehicle
      for the dissemination of research results. The search was conducted in July 2016,
      applying the truncated search term 'implant*' to locate original articles on
      implantology and its derivative forms. The search was conducted within the topic
      field (title, keywords and abstract) and two inclusion criteria were applied:
      documents denominated as articles were included; and articles categorized as Web
      of Science Medicine Dentistry and Oral Surgery. Finally only articles for which
      one of the participating organizations was located in Spain were selected.
      RESULTS: The final search identified a total of 774 records. The period 1988 to
      2015 saw an exponential growth in scientific production, especially during the
      last 10 years. Clinical Oral Implants Research and Medicina Oral Patologia Oral y
      Cirugia Bucal (Oral Medicine, Oral Pathology, and Oral Surgery) were the most
      productive journals. Collaborative networks among authors and among institutions
      increased and this increase was related to the improving quality of the
      publications. CONCLUSIONS: Bibliometric analysis revealed a significant growth in
      the quantity and quality of Spanish implantology literature. Most key
      bibliometric indicators demonstrated upward trends. Key words:Bibliometric
      analysis, publication, keywords, implantology, implant.

PMID- 28512551
TI  - Consensus statements and clinical recommendations on treatment indications,
      surgical procedures, prosthetic protocols and complications following All-On-4
      standard treatment. 9th Mozo-Grau Ticare Conference in Quintanilla, Spain.
AB  - OBJECTIVES: The present consensus report critically evaluates the scientific
      evidence based on a comprehensive systematic review of the All-On-4 treatment
      concept, focusing primarily on the treatment indications, surgical procedures and
      prosthetic protocols, and secondarily on the mechanical and biological
      complications involved. MATERIAL AND METHODS: A systematic review was made in
      advance of the meeting. Consensus statements, treatment guidelines and
      recommendations for future research were based on within-group as well as plenary
      debates and discussions of the systematic review. RESULTS: The main indication of
      All-On-4 standard care is an atrophic maxilla or mandible, with or without
      remnant hopeless tooth. in ASA I or II patients. This surgical-prosthetic
      protocol seems efficient, safe and effective in the case of Cawood & Howell class
      IV, V and VI. It is necessary for the implant to have had an insertion torque of
      over 35 Ncm for immediate loading. The provisional prosthesis should provide
      rigidity, being non-flexible in order to avoid micro-movements, and should be
      strong enough to not fracture. Balanced occlusion without interferences is
      required, ensuring very gentle dynamic movements. The design of the definitive
      prosthesis must be cleanable and biomechanically adjusted to the implant position
      and individual characteristics of each patient. A non-concave acrylic base
      resting over soft tissue is recommended, facilitating hygiene. Regarding
      occlusion, a group guide should be made, taking into account whether the
      antagonist is not a removable complete denture. In that case, bi-balanced
      occlusion should be assessed. Prosthetic complications occur as a result of
      fractures of the provisional acrylic prostheses. These problems in turn can be
      resolved by repair through relining or fixing. The most frequent biological
      complication is the loss of at least one implant, while the second most frequent
      complication is the development of peri-implantitis and mucositis. CONCLUSIONS:
      In the treatment of atrophy for full-arch implant supported restorations it is
      considered that four implants suffice for immediate loading and the final
      prosthesis, even when there is available bone between the mental foramina or
      maxillary sinuses. The weakness of the quality of the available evidence
      indicates that further studies are needed, involving an appropriate design and
      with adequate follow-up in All-On-4 standard care to confirm the present results
      mainly in relation to survival rates and complications. Key words:Atrophic jaw,
      All-on-4, immediate implant loading, edentulous mandible, edentulous maxilla,
      tilted implant, implant failure, dental implants.

PMID- 28512553
TI  - Juxtacortical Mandibular Chondrosarcoma during pregnancy: A case report.
AB  - Chondrosarcoma is one of the most common malignant bone tumors in adults. It use
      to affect upper arm, pelvis and thigh bone. A wide surgical extirpation represent
      the gold standard to treat this disorder. In fact, radiotherapy and chemotherapy
      are no useful. Interestingly, chondrosarcoma is rare in head and neck (HNCS) and
      extremely uncommon during pregnancy. Thus, there is a lack of evidence about the
      proper treatment in these cases. A wide surgical extirpation is also considered
      the most effective procedure in HNCS. There are no consistent evidences about the
      he role of radiation and chemotherapy. In view of that, the present study
      describes a case of juxtacortical mandibular chondrosarcoma affecting a 28-year
      old pregnant woman. After a multidisciplinary analysis of the case, we decided to
      treat the patient with a wide surgical resection and and immediately
      reconstruction. Key words:Mandibular chondrosarcoma, pregnancy, surgical
      extirpation, radiotherapy, chemoteraphy.

PMID- 28512552
TI  - Ability of salivary biomarkers in the prognostic of systemic and buccal
      inflammation.
AB  - Nowadays, there is a growing interest in using saliva as an alternative sample
      for the diagnosis, prediction and progression of several diseases. It has been
      established that some molecules found in saliva are related to oral inflammatory
      processes and systemic health status. Furthermore, it is known that saliva is
      crucial for the carrying out of different functions in the oral cavity and its
      role in the local modulation of inflammatory and immune response is being
      thoroughly studied by the health research community. The aim of this review is to
      analyze the most important biomarkers which have been utilized in biomedicine
      during the last two decades in order to establish a correlation between certain
      specific salivary biomarkers and systemic inflammation. Then, we discuss the
      utility of total proteins, immunoglobulin A and alpha-amylase as biomarkers for
      the prognostic of local inflammation after oral surgery. Key words:Inflammation,
      salivary biomarkers, systemic disease, buccal surgery, total proteins,
      inmunoglobulin A, Alpha-amylase.

PMID- 28512554
TI  - A case report on dental management of a toddler with Pachygyria.
AB  - Children with special health care needs receive less oral care than the normal
      population, inspite of the high level of dental diseases among them. They are at
      an increased risk for oral diseases throughout their lifetime. This paper reports
      a case of a toddler with congenital unusual thick convolutions of the cortex
      resulting in a condition called pachygyria. Intra oral examination showed
      multiple abscesses with poor oral hygiene. As the patient was lacking cooperative
      ability, treatment of full mouth rehabilitation as needed. The parents were
      advised for regular dental check-ups and informed about maintenance of good oral
      hygiene. This case report demonstrates the importance of oral hygiene maintenance
      of special children and also about their short and long term dental treatment
      protocol for maintaining good oral health. Key words:Pachygyria, general
      anaesthesia, special child, health care needs, preventive measures.

PMID- 28512555
TI  - Assessment of Obesity and Hepatic Late Adverse Effects in the Egyptian Survivors
      of Pediatric Acute Lymphoblastic Leukemia: a Single Center Study.
AB  - BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates
      reaching 80% emphasizes the necessity to determine treatment-related long-term
      effects. The aim of this study is to estimate the prevalence of overweight,
      obesity, and hepatic late adverse effects in a cohort of ALL survivors treated at
      the Hematology and Oncology Unit, Pediatrics Department, Menoufia University,
      Egypt. METHODS: In this case-control study, height, weight, and body mass index
      (BMI) were assessed for 35 pediatric ALL survivors and 35 healthy children. These
      parameters were plotted on the growth and WHO standard deviation charts for both
      males and females. Overweight and obesity were defined by BMI > 85th and 95th
      percentile respectively. Laboratory investigations were done in the form of iron
      profile, liver enzymes, total and direct bilirubin levels, serum urea &creatinine
      and detection of hepatitis C virus antibodies by ELISA. RESULTS: The weight and
      BMI were significantly greater in the survivors than controls (P value =0.002 and
      0.039 respectively). ALT, total & direct bilirubin, serum ferritin and
      transferrin saturation were considerably higher in the survivors than the
      controls (P value = 0.03, 0.036, 0.044, 0.006 and 0.03 respectively). Ten (28.6%)
      of survivors had hepatitis C antibodies with none (0%) of controls (P value
      =0.02). CONCLUSIONS: Pediatric ALL survivors are at increased risk of
      overweight/obesity, hepatic dysfunction in the form of elevated liver enzymes,
      bilirubin levels, and C viral hepatitis. Screening of those survivors for such
      complications should be considered.

PMID- 28512556
TI  - Pediatric Tuberculosis in Northern Sardinia.
AB  - BACKGROUND AND OBJECTIVES: Migration flux is an increasing phenomenon in Italy,
      and it raises several public health issues and concerns in pediatric infectious
      diseases. This study investigated the clinical characteristics and outcomes of a
      pediatric population at high-risk for tuberculosis (TB) and the potential role of
      immigration as a risk factor. DESIGN: We performed an observational retrospective
      study of children referred to the only Pediatric Infectious Diseases Unit for
      Northern Sardinia over a 6-year-period (2009-2014). Main variables assessed
      included TB skin test (TST), confirmed by quantiFERON Gold in Tube test, thorax X
      ray (TX), microbiological culture, direct microscopy for acid-fast bacilli and
      molecular assays. RESULTS: Of the 246 children (mean age = 5.8 +/- 3.9 years)
      identified, 222 (90.2%) were native to Sardinia and 24 (9.8%) were immigrants.
      The majority of children (n=205; 83%) were TB-exposed but not infected based on a
      negative TST and TX. Among the TST positive group (n= 39; 16%), 19 (49%) had
      latent TB (TX negative), while 20 (51%) had active TB (TX positive). The percent
      of TST positive children was significantly higher in the immigrant than the
      native group (42.5% versus 14%, p<0.001). Clinical presentations included
      pulmonary involvement with hilar lymphadenopathy (72%), pleurisy (13,5%), lateral
      cervical lymphadenopathy (9%), pneumonia with calcifications (4.5%) and
      disseminated TB (4.5%). One child had multidrug-resistant tuberculosis.
      CONCLUSIONS: Pediatric TB represents a relevant and potentially worsening public
      health problem in Northern Sardinia. A strict surveillance system and appropriate
      treatment can prevent the most severe forms and reduce TB transmission.

PMID- 28512557
TI  - Increased Vasoocclusive Crises in "O" Blood Group Sickle Cell Disease Patients:
      Association with Underlying Thrombospondin Levels.
AB  - OBJECTIVES: To explore the incidence of vaso-occlusive crisis (VOC) in Blood
      Group "O" sickle cell disease (SCD) patients, and correlate it with the blood
      group and thrombospondin (TSP) levels. METHODS: In 89 consecutive SCD patients,
      blood samples were obtained for von Williebrand factor (vWF:Ag) antigen, collagen
      binding activity (CBA), ristocetin binding activity (RCo), blood group typing, C
      reactive protein (CRP), high performance liquid chromatography (HPLC), Serum TSP
      1 and TSP 2 levels, complete blood counts (CBC), lactic dehydrogenase (LDH)
      levels, liver function (LFT) and renal function tests (RFT) during VOC episodes
      and in steady state conditions. RESULTS: In steady state SCD patients (n=72), "O"
      blood group patients (n=37) showed a significantly higher median serum TSP 1 and
      TSP 2 levels as compared to non-O blood group patients [n=35] [p <0.05, Mann
      Whitney test]; with an inverse relation between vWF:Ag, Factor VIII:C and TSP
      levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher
      in patients presenting with acute VOC [n=17], as well as in those with repeated
      VOC's (group 1, n=16), especially amongst blood group "O" patients [p, <0.05,
      Mann-Whitney test]. CONCLUSIONS: The study demonstrates an inverse relation
      between TSP and vWF levels, in blood group "O" SCD patients, with an upregulation
      of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2
      levels were significantly elevated.

PMID- 28512558
TI  - FDG-PET Scan: a new Paradigm for Follicular Lymphoma Management.
AB  - In the present review, the reader will be led to the most relevant observations
      that prompted oncologists and haematologist to consider FDG-PET/CT as a new
      paradigm for FL management in clinical practice. The role of functional imaging
      in lymphoma staging, restaging, prognostication, and metabolic tumour volume
      computing will be reviewed in detail. Moreover, a special focus will be addressed
      to technical and practical aspects of PET scan reporting, which have been set
      during the last decade to ensure the reproducibility of the therapeutic results.
      Finally, the predictive role of PET/CT on long-term treatment outcome will be
      compared with another well-known prognosticator as minimal residual disease (MRD)
      detection by Immunoglobulin gene rearrangement assessment.

PMID- 28512559
TI  - Spirometric Evaluation of Pulmonary Function in Nigerian Children underwent Bone
      Marrow Transplantation for Sickle Cell Anemia.

PMID- 28512560
TI  - The Start-Up of the first Hematopoietic Stem Cell Transplantation Center in the
      Iraqi Kurdistan: a Capacity-Building Cooperative Project by the Hiwa Cancer
      Hospital, Sulaymaniyah, and the Italian Agency for Development Cooperation: an
      Innovative Approach.
AB  - We describe the entire process leading to the start-up of a hematopoietic stem
      cell transplantation center at the Hiwa Cancer Hospital, in the city of
      Sulaymaniyah, Kurdistan Iraqi Region. This capacity building project was funded
      by the Italian Development Cooperation Agency and implemented with the support of
      the volunteer work of Italian professionals, either physicians, nurses,
      biologists and technicians. The intervention started in April 2016, was based
      exclusively on training and coaching on site, that represent a significant
      innovative approach, and led to a first autologous transplant in June 2016 and to
      the first allogeneic transplant in October. At the time of reporting, 9 months
      from the initiation of the project, 18 patients have been transplanted, 15 with
      an autologous and 3 with an allogeneic graft. The center at the HCH represents
      the first transplantation center in Kurdistan and the second in wide Iraq. We
      conclude that international development cooperation may play an important role
      also in the field of high-technology medicine, and contribute to improved local
      centers capabilities through country to country scientific exchanges. The
      methodology to realize this project is innovative, since HSCT experts are brought
      as volunteers to the center(s) to be started, while traditionally it is the
      opposite, i.e. the local professionals to be trained are brought to the
      specialized center(s).

PMID- 28512561
TI  - Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and
      Progenitor Cells.
AB  - Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the
      bone marrow is a complex process with a critical role in repopulation of the bone
      marrow after transplantation. This active process allows for migration of HSC
      from peripheral blood and their successful anchoring in bone marrow before
      proliferation. The process of engraftment starts with the onset of proliferation
      and must, therefore, be functionally dissociated from the former process. In this
      overview, we analyze the characteristics of stem cells (SCs) with particular
      emphasis on their plasticity and ability to find their way home to the bone
      marrow. We also address the problem of graft failure which remains a significant
      contributor to morbidity and mortality after allogeneic hematopoietic stem cell
      transplantation (HSCT). Within this context, we discuss non-malignant and
      malignant hematological disorders treated with reduced-intensity conditioning
      regimens or grafts from human leukocyte antigen (HLA)-mismatched donors.

PMID- 28512563
TI  - Acquired von Willebrand Syndrome Associated to Secondary IgM MGUS Emerging after
      Autologous Stem Cell Transplantation for AL Amyloidosis.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that
      occurs in patients with no prior personal or family history of bleeding. Here, we
      describe a case of AVWS occurring after autologous stem cell transplantation
      (ASCT). Interestingly, AVWS developed after bortezomib-based induction and
      conditioning regimens. Recent evidence suggests that the proximity of the
      bortezomib therapy to the collection of stem cells with consequent depletion of
      regulatory T cells after the conditioning regimen could explain some of the
      unusual autoimmune complications reported in patients receiving bortezomib prior
      to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which
      may have also contributed to the AVWS. To the best of our knowledge, this is the
      first case of post-ASCT AVWS reported. Prospective data is needed to better
      elucidate the mechanisms by which these unusual complications occur in patients
      receiving bortezomib prior to ASCT.

PMID- 28512562
TI  - Morphologic Confounders and CD19 Negativity in a Case of Hairy Cell Leukemia.
AB  - OBJECTIVES: We report a case of hairy cell leukemia (HCL) initially misdiagnosed
      as plasma cell dyscrasia due to various clinical, morphological and
      immunophenotypic confounders. METHODS AND RESULTS: In a patient diagnosed of
      marrow plasmacytosis and serum monoclonal protein elsewhere and referred to our
      hospital, morphological evaluation of bone marrow aspirate smears and trephine
      biopsy, immunophenotyping, and molecular testing (BRAFV600E mutation) were done.
      Clinically, the patient was asymptomatic; bone marrow revealed plasmacytosis,
      mastocytosis, and lymphocytosis with a few "hairy" cells. Immunophenotyping
      showed features of HCL with aberrant CD10 expression and a large subclone of
      CD19neg cells. A diagnosis of HCL with reactive plasmacytosis and mast cell
      hyperplasia was made and confirmed by immunophenotyping and molecular studies.
      CONCLUSION: Hematopathologists must be aware of various confounding factors and
      should judiciously use flow cytometric and molecular studies for attaining a
      proper diagnosis of HCL. We also report a very rare immunophenotypic aberrancy
      (CD 19 negativity) in HCL.

PMID- 28512565
TI  - Developments in the structural science of materials.
AB  - Recent developments in the structural science of materials and the growing power
      of computational methods in this field are discussed.

PMID- 28512564
TI  - Infections and Follicular Lymphoma: is there a Link?
AB  - Several infectious agents appear to provide a proliferative signal -- "antigen
      drive" - that could be implicated in the pathogenesis of various type of Non
      Hodgkin Lymphoma (NHL). A classical model of the infection-driven
      lymphoproliferative disorder is Helicobacter pylori-induced gastric MALT
      lymphoma, where antibiotic therapy allows the eradication of both the infectious
      agent and the clonal B-cell expansion. Following the footsteps of this example,
      several retrospective studies have found a correlation with other pathogens and B
      cell Lymphomas, adding new relevant information about pathogenesis and laying the
      groundwork for chemotherapy-free treatments. Although no clear association has
      been found between infectious agents and Follicular Lymphoma (FL), a growing
      number of biological and clinical observations suggests the interaction of
      physiological and pathological microbial populations also in this subtype of
      lymphoma. In the last few years, epidemiological studies investigating the
      association of known risk factors and FL found a potential correlation with viral
      or bacterial infections; moreover, recent findings of the stimulation of FL
      clones support the importance of microbial exposure to lymphomagenesis and
      disease progression. In the following review we make an attempt to find tangible
      evidence for a role of either physiological and pathological exogenous microbial
      species in the pathogenesis of FL, and try to integrate the findings coming from
      epidemiological, biological and interventional studies to define future novel
      treatment and prevention strategies for FL.

PMID- 28512566
TI  - Regulating thermosalient behaviour in three polymorphs.
AB  - Three polymorphs of a di-chloro-N-salicylideneaniline derivative show visually
      impressive jumping and sudden blasting behaviours on heating due to phase
      transitions.

PMID- 28512567
TI  - How many tricks can an old perovskite play?
AB  - The ferroelectric-paraelectric transition in Li0.2Na0.8NbO3 is between two
      extremely rare perovskite polytypes. How the unprecedented sequence of structures
      was established shows that even old oxides can play new tricks.

PMID- 28512568
TI  - Acemetacin cocrystal structures by powder X-ray diffraction.
AB  - Cocrystals of acemetacin drug (ACM) with nicotinamide (NAM), p-aminobenzoic acid
      (PABA), valerolactam (VLM) and 2-pyridone (2HP) were prepared by melt
      crystallization and their X-ray crystal structures determined by high-resolution
      powder X-ray diffraction. The powerful technique of structure determination from
      powder data (SDPD) provided details of molecular packing and hydrogen bonding in
      pharmaceutical cocrystals of acemetacin. ACM-NAM occurs in anhydrate and hydrate
      forms, whereas the other structures crystallized in a single crystalline form.
      The carboxylic acid group of ACM forms theacid-amide dimer three-point synthon
      R32(9)R22(8)R32(9) with three different syn amides (VLM, 2HP and caprolactam).
      The conformations of the ACM molecule observed in the crystal structures differ
      mainly in the mutual orientation of chlorobenzene fragment and the neighboring
      methyl group, being anti (type I) or syn (type II). ACM hydrate, ACM-NAM, ACM-NAM
      hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas
      ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen
      bond interactions in all the crystal structures were quantified by calculating
      their molecular electrostatic potential (MEP) surfaces. Hirshfeld surface
      analysis of the cocrystal surfaces shows that about 50% of the contribution is
      due to a combination of strong and weak O?H, N?H, Cl?H and C?H interactions. The
      physicochemical properties of these cocrystals are under study.

PMID- 28512569
TI  - Unprecedented phase transition sequence in the perovskite Li0.2Na0.8NbO3.
AB  - The perovskite Li0.2Na0.8NbO3 is shown, by powder neutron diffraction, to display
      a unique sequence of phase transitions at elevated temperature. The ambient
      temperature polar phase (rhombohedral, space group R3c) transforms via a first
      order transition to a polar tetragonal phase (space group P42mc) in the region
      150-300 degrees C; these two phases correspond to Glazer tilt systems a-a-a- and
      a+a+c-, respectively. At 500 degrees C a ferroelectric-paraelectric transition
      takes place from P42mc to P42/nmc, retaining the a+a+c- tilt. Transformation to a
      single-tilt system, a0a0c+ (space group P4/mbm), occurs at 750 degrees C, with
      the final transition to the aristotype cubic phase at 850 degrees C. The P42mc
      and P42/nmc phases have each been seen only once and twice each, respectively, in
      perovskite crystallography, in each case in compositions prepared at high
      pressure.

PMID- 28512570
TI  - The structure of denisovite, a fibrous nanocrystalline polytypic disordered 'very
      complex' silicate, studied by a synergistic multi-disciplinary approach employing
      methods of electron crystallography and X-ray powder diffraction.
AB  - Denisovite is a rare mineral occurring as aggregates of fibres typically 200-500
      nm diameter. It was confirmed as a new mineral in 1984, but important facts about
      its chemical formula, lattice parameters, symmetry and structure have remained
      incompletely known since then. Recently obtained results from studies using
      microprobe analysis, X-ray powder diffraction (XRPD), electron crystallography,
      modelling and Rietveld refinement will be reported. The electron crystallography
      methods include transmission electron microscopy (TEM), selected-area electron
      diffraction (SAED), high-angle annular dark-field imaging (HAADF), high
      resolution transmission electron microscopy (HRTEM), precession electron
      diffraction (PED) and electron diffraction tomography (EDT). A structural model
      of denisovite was developed from HAADF images and later completed on the basis of
      quasi-kinematic EDT data by ab initio structure solution using direct methods and
      least-squares refinement. The model was confirmed by Rietveld refinement. The
      lattice parameters are a = 31.024 (1), b = 19.554 (1) and c = 7.1441 (5) A, beta
      = 95.99 (3) degrees , V = 4310.1 (5) A3 and space group P12/a1. The structure
      consists of three topologically distinct dreier silicate chains, viz. two
      xonotlite-like dreier double chains, [Si6O17]10-, and a tubular loop-branched
      dreier triple chain, [Si12O30]12-. The silicate chains occur between three walls
      of edge-sharing (Ca,Na) octahedra. The chains of silicate tetrahedra and the
      octahedra walls extend parallel to the z axis and form a layer parallel to (100).
      Water molecules and K+ cations are located at the centre of the tubular silicate
      chain. The latter also occupy positions close to the centres of eight-membered
      rings in the silicate chains. The silicate chains are geometrically constrained
      by neighbouring octahedra walls and present an ambiguity with respect to their z
      position along these walls, with displacements between neighbouring layers being
      either Deltaz = c/4 or -c/4. Such behaviour is typical for polytypic sequences
      and leads to disorder along [100]. In fact, the diffraction pattern does not show
      any sharp reflections with l odd, but continuous diffuse streaks parallel to a*
      instead. Only reflections with l even are sharp. The diffuse scattering is caused
      by (100) nano-lamellae separated by stacking faults and twin boundaries. The
      structure can be described according to the order-disorder (OD) theory as a
      stacking of layers parallel to (100).

PMID- 28512571
TI  - Mechanochemical synthesis of N-salicylidene-aniline: thermosalient effect of
      polymorphic crystals.
AB  - Polymorphs of the dichloro derivative of N-salicylideneaniline exhibit mechanical
      responses such as jumping (Forms I and III) and exploding (Form II) in its three
      polymorphs. The molecules are connected via the amide N-H?O dimer synthon and C
      Cl?O halogen bond in the three crystal structures. A fourth high-temperature Form
      IV was confirmed by variable-temperature single-crystal X-ray diffraction at 180
      degrees C. The behaviour of jumping exhibited by the polymorphic crystals of
      Forms I and III is due to the layered sheet morphology and the transmission of
      thermal stress in a single direction, compared with the corrugated sheet
      structure of Form II such that heat dissipation is more isotropic causing
      blasting. The role of weak C-Cl?O interactions in the thermal response of
      molecular crystals is discussed.

PMID- 28512572
TI  - Experimental strategies for imaging bioparticles with femtosecond hard X-ray
      pulses.
AB  - This study explores the capabilities of the Coherent X-ray Imaging Instrument at
      the Linac Coherent Light Source to image small biological samples. The weak
      signal from small samples puts a significant demand on the experiment.
      Aerosolized Omono River virus particles of ~40 nm in diameter were injected into
      the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were
      recorded on two area detectors. The statistical nature of the measurements from
      many individual particles provided information about the intensity profile of the
      X-ray beam, phase variations in the wavefront and the size distribution of the
      injected particles. The results point to a wider than expected size distribution
      (from ~35 to ~300 nm in diameter). This is likely to be owing to nonvolatile
      contaminants from larger droplets during aerosolization and droplet evaporation.
      The results suggest that the concentration of nonvolatile contaminants and the
      ratio between the volumes of the initial droplet and the sample particles is
      critical in such studies. The maximum beam intensity in the focus was found to be
      1.9 * 1012 photons per um2 per pulse. The full-width of the focus at half-maximum
      was estimated to be 500 nm (assuming 20% beamline transmission), and this width
      is larger than expected. Under these conditions, the diffraction signal from a
      sample-sized particle remained above the average background to a resolution of
      4.25 nm. The results suggest that reducing the size of the initial droplets
      during aerosolization is necessary to bring small particles into the scope of
      detailed structural studies with X-ray lasers.

PMID- 28512573
TI  - Photoreduction and validation of haem-ligand intermediate states in protein
      crystals by in situ single-crystal spectroscopy and diffraction.
AB  - Powerful synergies are available from the combination of multiple methods to
      study proteins in the crystalline form. Spectroscopies which probe the same
      region of the crystal from which X-ray crystal structures are determined can give
      insights into redox, ligand and spin states to complement the information gained
      from the electron-density maps. The correct assignment of crystal structures to
      the correct protein redox and ligand states is essential to avoid the
      misinterpretation of structural data. This is a particular concern for haem
      proteins, which can occupy a wide range of redox states and are exquisitely
      sensitive to becoming reduced by solvated electrons generated from interactions
      of X-rays with water molecules in the crystal. Here, single-crystal spectroscopic
      fingerprinting has been applied to investigate the laser photoreduction of ferric
      haem in cytochrome c'. Furthermore, in situ X-ray-driven generation of haem
      intermediates in crystals of the dye-decolourizing-type peroxidase A (DtpA) from
      Streptomyces lividans is described.

PMID- 28512574
TI  - Crystallographic and SAXS studies of S-adenosyl-l-homocysteine hydrolase from
      Bradyrhizobium elkanii.
AB  - S-Adenosyl-l-homocysteine hydrolase (SAHase) from the symbiotic bacterium
      Bradyrhizobium elkanii (BeSAHase) was crystallized in four ligand complexes with
      (i) mixed adenosine (Ado) and cordycepin (Cord; 3'-deoxyadenosine), (ii) adenine
      (Ade), (iii) Ado and (iv) mixed 2'-deoxyadenosine (2'-dAdo) and Ade. The crystal
      structures were solved at resolutions of 1.84, 1.95, 1.95 and 1.54 A,
      respectively. Only the Ade complex crystallized with a dimer in the asymmetric
      unit, while all of the other complexes formed a crystallographically independent
      tetrameric assembly. In the Ado/Cord complex, adenosine is found in three
      subunits while the fourth subunit has cordycepin bound in the active site. In the
      Ade and Ado complexes only these ligand molecules are present in the active
      sites. The 2'-dAdo/Ade complex has Ade bound in two subunits and 2'-dAdo bound in
      the other two subunits. The BeSAHase fold adopted a closed conformation in the
      complexes with Ado, Ade and 2'-dAdo, and a semi-open conformation when cordycepin
      occupied the active site. An SAHase-specific molecular gate, consisting of
      residues His342 and Phe343, behaves differently in the different complexes, but
      there is no simple correlation with the ligand type. Additional small-angle X-ray
      scattering (SAXS) experiments confirm the tetrameric state of the protein in
      solution. The main conclusions from this work are (i) that the SAHase subunit
      does not simply oscillate between two discrete conformational open/closed states
      in correlation with the absence/presence of a ligand in the active site, but can
      also assume an intermediate form for some ligands; (ii) that the shut/open state
      of the molecular gate in the access channel to the active site is not correlated
      in a simple way with the open/closed subunit conformation or empty/occupied
      status of the active site, but that a variety of states are possible even for the
      same ligand; (iii) that a cation (typically sodium) coordinated in an
      intersubunit loop rigidifies a molecular hinge and thus stabilizes the closed
      conformation; (iv) that BeSAHase in solution is a tetramer, consistent with the
      model derived from crystallography.

PMID- 28512575
TI  - New leads for fragment-based design of rhenium/technetium radiopharmaceutical
      agents.
AB  - Multiple possibilities for the coordination of fac-[Re(CO)3(H2O)3]+ to a protein
      have been determined and include binding to Asp, Glu, Arg and His amino-acid
      residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro.
      The large number of rhenium metal complex binding sites that have been identified
      on specific residues thereby allow increased target identification for the design
      of future radiopharmaceuticals. The core experimental concept involved the use of
      state-of-art tuneable synchrotron radiation at the Diamond Light Source to
      optimize the rhenium anomalous dispersion signal to a large value (f'' of 12.1
      electrons) at its LI absorption edge with a selected X-ray wavelength of 0.9763
      A. At the Cu Kalpha X-ray wavelength (1.5418 A) the f'' for rhenium is 5.9
      electrons. The expected peak-height increase owing to the optimization of the Re
      f'' was therefore 2.1. This X-ray wavelength tuning methodology thereby showed
      the lower occupancy rhenium binding sites as well as the occupancies of the
      higher occupancy rhenium binding sites.

PMID- 28512577
TI  - Genetic changes found in a distinct clade of Enterovirus D68 associated with
      paralysis during the 2014 outbreak.
AB  - Enterovirus D68 (EV-D68) caused a severe respiratory illness outbreak in the
      United States in 2014. Reports of acute flaccid myelitis (AFM)/paralysis (AFP) in
      several independent epidemiological clusters of children with detectable EV-D68
      have raised concerns that genetic changes in EV-D68 could be causing increased
      disease severity and neurological symptoms. To explore the potential link between
      EV-D68 genetic variations and symptom changes, we performed a series of
      comparative genomic analyses of EV-D68 2014 outbreak isolate sequences using data
      and analytical tools in the Virus Pathogen Resource (ViPR; www.viprbrc.org). Our
      results suggest that (1) three distinct lineages of EV-D68 were co-circulating in
      2013 and 2014; (2) isolates associated with AFM/AFP belong to a single
      phylogenetic subclade - B1; (3) the majority of isolates from the B1 subclade
      have 21 unique substitutions that distinguish them from other isolates, including
      amino acid substitutions in the VP1, VP2, and VP3 capsid proteins and the 3D RNA
      dependent RNA polymerase, and nucleotide substitutions in the internal ribosome
      entry sequence (IRES); (4) at 12 of these positions, B1 isolates carry the same
      residues observed at equivalent positions in paralysis-causing enteroviruses,
      including poliovirus, EV-D70 and EV-A71. Based on these results, we hypothesize
      that unique B1 substitutions may be responsible for the apparent increased
      incidence of neuropathology associated with the 2014 outbreak.

PMID- 28512576
TI  - Applications of contact predictions to structural biology.
AB  - Evolutionary pressure on residue interactions, intramolecular or intermolecular,
      that are important for protein structure or function can lead to covariance
      between the two positions. Recent methodological advances allow much more
      accurate contact predictions to be derived from this evolutionary covariance
      signal. The practical application of contact predictions has largely been
      confined to structural bioinformatics, yet, as this work seeks to demonstrate,
      the data can be of enormous value to the structural biologist working in X-ray
      crystallo-graphy, cryo-EM or NMR. Integrative structural bioinformatics packages
      such as Rosetta can already exploit contact predictions in a variety of ways. The
      contribution of contact predictions begins at construct design, where structural
      domains may need to be expressed separately and contact predictions can help to
      predict domain limits. Structure solution by molecular replacement (MR) benefits
      from contact predictions in diverse ways: in difficult cases, more accurate
      search models can be constructed using ab initio modelling when predictions are
      available, while intermolecular contact predictions can allow the construction of
      larger, oligomeric search models. Furthermore, MR using supersecondary motifs or
      large-scale screens against the PDB can exploit information, such as the parallel
      or antiparallel nature of any beta-strand pairing in the target, that can be
      inferred from contact predictions. Contact information will be particularly
      valuable in the determination of lower resolution structures by helping to assign
      sequence register. In large complexes, contact information may allow the identity
      of a protein responsible for a certain region of density to be determined and
      then assist in the orientation of an available model within that density. In NMR,
      predicted contacts can provide long-range information to extend the upper size
      limit of the technique in a manner analogous but complementary to experimental
      methods. Finally, predicted contacts can distinguish between biologically
      relevant interfaces and mere lattice contacts in a final crystal structure, and
      have potential in the identification of functionally important regions and in
      foreseeing the consequences of mutations.

PMID- 28512578
TI  - Safety and Efficacy of Microinvasive Glaucoma Surgery.
AB  - Microinvasive glaucoma surgery (MIGS) is emerging as a new therapeutic option for
      glaucoma patients who wish to reduce their medication burden and avoid the
      postoperative complications of conventional glaucoma filtration surgery. These
      devices differ in terms of their efficacy and safety profile. Schlemm's canal
      devices have the most favorable safety profile at the compromise of modest
      efficacy, while subconjunctival and suprachoroidal devices are potentially more
      effective at lowering the intraocular pressure at the expense of a higher rate of
      complications. This review consolidates the latest evidence on the efficacy and
      safety of the MIGS devices in clinical use and provides an overview on upcoming
      devices which would likely also become viable treatment options in the near
      future. These clinical data would assist a glaucoma surgeon in selecting the most
      appropriate MIGS device for each patient based on the glaucoma severity and
      patient expectations.

PMID- 28512579
TI  - The Impact of Electronic Reading Devices on Reading Speed and Comfort in Patients
      with Decreased Vision.
AB  - Background/Aims. To evaluate the impact of back-illuminated and nonilluminated
      electronic reading devices on reading speed and comfort in patients with
      decreased vision. Methods. A prospective study involving a convenience sample of
      167 patients at a single retina practice from January 2011 to December 2012.
      Participants were asked to read five different excerpts on five different media
      in a randomly assigned order. Media included a printed book at 12-point font
      (12PF), iPad2 at 12PF, iPad2 at 18-point font (18PF), Kindle2 at 12PF, and
      Kindle2 at 18PF. Reading speed in words per minute (WPM) and medium preference
      were recorded and stratified by visual acuity (VA). Results. Mean reading speeds
      in WPM: iPad2 at 18PF (217.0), iPad2 at 12PF (209.1), Kindle2 at 18PF (183.3),
      Kindle2 at 12PF (177.7), and printed book at 12PF (176.8). Reading speed was
      faster on back-illuminated media compared to nonilluminated media. Text
      magnification minimized losses in reading performance with worsening patient VA.
      The majority of participants preferred reading on the iPad2 at 18PF. Conclusions.
      Back-illuminated devices may increase reading speed and comfort relative to
      nonilluminated devices and printed text, particularly in patients with decreased
      VA.

PMID- 28512581
TI  - Refractive Lens Exchange Combined with Primary Posterior Vitrectorhexis in Highly
      Myopic Patients.
AB  - Purpose. To evaluate efficacy and safety of primary vitrectorhexis for posterior
      capsulotomy in highly myopic patients undergoing refractive lens exchange.
      Methods. The study is a prospective nonrandomized interventional study. The study
      comprised 60 eyes of 60 myopic patients. All patients underwent refractive lens
      exchange (RLE) and foldable IOL implantation combined with primary posterior
      capsulotomy. We used a 23-gauge vitrectomy probe for the creation of the
      posterior capsule opening. We followed the patients for one year. Results. During
      surgery, the IOLs remained well centered in the capsular bag after creation of
      the capsulotomy. Postoperatively, we did not report any complications related to
      lens centration or changes in the posterior capsulotomy size. No eye required YAG
      laser posterior capsulotomy and no cases of retinal detachment (RD) occurred
      during the follow-up period. Conclusion. Primary posterior vitrectorhexis during
      RLE is an efficient method in preventing the occurrence of posterior capsular
      opacification (PCO) and the need for YAG laser posterior capsulotomy with its
      possible complications.

PMID- 28512580
TI  - High-Intensity Focused Ultrasound Circular Cyclocoagulation in Glaucoma: A Step
      Forward for Cyclodestruction?
AB  - The ciliary body ablation is still considered as a last resort treatment to
      reduce the intraocular pressure (IOP) in uncontrolled glaucoma. Several ablation
      techniques have been proposed over the years, all presenting a high rate of
      complications, nonselectivity for the target organ, and unpredictable dose-effect
      relationship. These drawbacks limited the application of cyclodestructive
      procedures almost exclusively to refractory glaucoma. High-intensity focused
      ultrasound (HIFU), proposed in the early 1980s and later abandoned because of the
      complexity and side effects of the procedure, was recently reconsidered in a new
      approach to destroy the ciliary body. Ultrasound circular cyclocoagulation (UC3),
      by using miniaturized transducers embedded in a dedicated circular-shaped device,
      permits to selectively treat the ciliary body in a one-step, computer-assisted,
      and non-operator-dependent procedure. UC3 shows a high level of safety along with
      a predictable and sustained IOP reduction in patients with refractory glaucoma.
      Because of this, the indication of UC3 was recently extended also to naive-to
      surgery patients, thus reconsidering the role and timing of ciliary body ablation
      in the surgical management of glaucoma. This article provides a review of the
      most used cycloablative techniques with particular attention to UC3, summarizing
      the current knowledge about this procedure and future possible developments.

PMID- 28512582
TI  - Factors Affecting Utilization of Voluntary HIV Counseling and Testing Services
      among Teachers in Awi Zone, Northwest Ethiopia.
AB  - HIV/AIDS affects the basic educational sector which is the most productive
      segment of the population and vital to the creation of human capital. The loss of
      skilled and experienced teachers due to the problem is increasingly compromising
      the provision of quality education in most African countries. The study was
      proposed to determine the magnitude of VCT utilization and assess contributing
      factors that affect VCT service utilization among secondary school teachers in
      Awi Zone. A cross-sectional study design was conducted among 588 participants in
      2014. Self-administered questionnaire was used to collect data. Data was analyzed
      using SPSS version 16, presented as frequencies and summary statistics, and
      tested for presence of significant association with odds ratio at 95% CI. More
      than half (53.6%) of study participants were tested for HIV. Those who had sexual
      intercourse, had good knowledge about VCT, were divorced/widowed, were in the age
      group of 20-29 years, and were married utilized VCT services two, three, four,
      three, and two times better than their counterparts, respectively. Actions
      targeting unmarried status, increase of educational level, and teachers with age
      groups above 30 years are necessary to follow their counterparts to utilize VCT
      service in order to save loss of teachers.

PMID- 28512583
TI  - Role of Transbronchial Lung Cryobiopsies in Diffuse Parenchymal Lung Diseases:
      Interest of a Sequential Approach.
AB  - Background. Transbronchial lung cryobiopsies (TBLCs) are a promising diagnostic
      tool in the setting of diffuse parenchymal lung diseases (DPLDs). However, no
      comparison with surgical lung biopsy (SLB) in the same patient is available.
      Methods. The diagnostic yield and safety data of TBLCs, as well as the result of
      SLB performed after TBLCs, were analysed in a multicentric Belgian study. A SLB
      was performed after TBLCs in absence of a definite pathological diagnosis or if a
      NSIP pattern was observed without related condition identified following
      multidisciplinary discussion. Results. Between April 2015 and November 2016, 30
      patients were included. Frequent complications included pneumothorax (20%) and
      bleeding (severe 7%, moderate 33%, and mild 53%). There was no mortality. The
      overall diagnostic yield was 80%. A SLB was performed in six patients (three
      without definite histological pattern and three with an NSIP). The surgical
      biopsy changed the pathological diagnosis into a UIP pattern in five patients and
      confirmed a NSIP pattern in one patient. Conclusion. TBLCs are useful in the
      diagnostic work-up of DPLDs avoiding a SLB in 80% of the patients. However,
      surgical biopsies, performed as a second step after TBLCs because of an
      indefinite diagnosis or a NSIP pattern, provide additional information supporting
      the interest of a sequential approach in these patients.

PMID- 28512584
TI  - Neurorehabilitation: Neural Plasticity and Functional Recovery.

PMID- 28512586
TI  - Cryoablation for Ventricular Tachycardia Originating from Anterior Papillary
      Muscle of Left Ventricle Guided by Intracardiac Echocardiography.
AB  - Papillary muscles (PMs) were reported to be origin of ventricular arrhythmia
      (VA). Radiofrequency (RF) ablation was reported to be acutely effective in
      eliminating VA. However, the recurrence rate is high. Recently, cryoablation
      guided by intracardiac echocardiography, 3-dimensional mapping system, and image
      integration was introduced as alternative strategy for this challenging ablation.
      We present a case of ventricular tachycardia originating from anterior PM of left
      ventricle treated by cryoablation guided only by intracardiac echocardiography.

PMID- 28512587
TI  - Adenocarcinoma In Situ Arising from Brunner's Gland Treated by Endoscopic Mucosal
      Resection.
AB  - An 86-year-old Japanese man was presented to our hospital for further
      investigation of duodenal adenocarcinoma. The tumor was endoscopically resected.
      Pathological analysis revealed coexistence of gastric foveolar metaplasia and a
      surrounding hyperplastic Brunner's gland, in addition to an adenocarcinoma
      component. Immunostaining for MUC5AC and MUC6 confirmed the diagnosis of
      adenocarcinoma in situ arising from Brunner's gland hyperplasia. This case
      suggests that although detailed preoperative evaluation is required to determine
      the depth of tumor invasion, endoscopic resection may be a promising option for
      the treatment of adenocarcinomas arising from Brunner's gland hyperplasia.

PMID- 28512589
TI  - A Case of Early Disseminated Neurological Lyme Disease Followed by Atypical
      Cutaneous Manifestations.
AB  - Lyme disease (LD) is a tick-borne illness caused by Borrelia burgdorferi sensu
      stricto. An 80-year-old female from Pennsylvania, USA, presented to an outside
      hospital with fever, confusion, lower extremity weakness, and stool incontinence.
      CT head and MRI spine were unremarkable. An infectious work-up including lumbar
      puncture was negative. She was transferred to our tertiary care hospital. Patient
      was noted to have mild unilateral right-sided facial droop and a diffuse macular
      rash throughout the body. She denied any outdoor activities, tick bites, or
      previous rash. Intravenous ceftriaxone was started for suspected LD. The
      patient's symptoms including facial droop resolved within 24 hours of antibiotic
      therapy. Polymerase chain reaction of the blood, IgM ELISA, and IgM Western blot
      testing for LD came back positive a few days after initiation of therapy. She was
      treated for a total of 21 days for neurological LD with complete symptom
      resolution. Not all patients have the classic "targetoid" EM rash on initial
      presentation, rash could develop after neurological manifestations, and prompt
      initiation of antibiotics without awaiting serology is paramount to making a
      quick and a full recovery. There should be a high index of suspicion for early
      disseminated LD, as presentations can be atypical.

PMID- 28512588
TI  - Severe Aplastic Anemia following Parvovirus B19-Associated Acute Hepatitis.
AB  - Human parvovirus (HPV) B19 is linked to a variety of clinical manifestations,
      such as erythema infectiosum, nonimmune hydrops fetalis, and transient aplastic
      anemia. Although a few cases have shown HPVB19 infection as a possible causative
      agent for hepatitis-associated aplastic anemia (HAAA) in immunocompetent
      patients, most reported cases of HAAA following transient hepatitis did not have
      delayed remission. Here we report a rare case of severe aplastic anemia following
      acute hepatitis with prolonged jaundice due to HPVB19 infection in a previously
      healthy young male. Clinical laboratory examination assessed marked liver injury
      and jaundice as well as peripheral pancytopenia, and bone marrow biopsy revealed
      severe hypoplasia and fatty replacement. HPVB19 infection was diagnosed by enzyme
      immunoassay with high titer of anti-HPVB19 immunoglobulin M antibodies.
      Immunosuppressive therapy was initiated 2 months after the onset of acute
      hepatitis when liver injury and jaundice were improved. Cyclosporine provided
      partial remission after 2 months of medication without bone marrow
      transplantation. Our case suggests that HPVB19 should be considered as a
      hepatotropic virus and a cause of acquired aplastic anemia, including HAAA.

PMID- 28512585
TI  - Understanding the Mechanisms of Recovery and/or Compensation following Injury.
AB  - Injury due to stroke and traumatic brain injury result in significant long-term
      effects upon behavioral functioning. One central question to rehabilitation
      research is whether the nature of behavioral improvement observed is due to
      recovery or the development of compensatory mechanisms. The nature of functional
      improvement can be viewed from the perspective of behavioral changes or changes
      in neuroanatomical plasticity that follows. Research suggests that these changes
      correspond to each other in a bidirectional manner. Mechanisms surrounding
      phenomena like neural plasticity may offer an opportunity to explain how
      variables such as experience can impact improvement and influence the definition
      of recovery. What is more, the intensity of the rehabilitative experiences may
      influence the ability to recover function and support functional improvement of
      behavior. All of this impacts how researchers, clinicians, and medical
      professionals utilize rehabilitation.

PMID- 28512591
TI  - Sporadic Insulinoma as a Rare Cause of Recurrent Hypoglycemia in Children.
AB  - Insulinoma is a rare pancreatic tumor in children and adolescents. As a result of
      insulin hypersecretion, signs and symptoms are more commonly consequences of the
      pathophysiologic responses to hypoglycemia. According to rarity of this tumor in
      children and nonspecificity of clinical presentations, diagnosis of insulinoma in
      this group of patients is usually delayed. Early diagnosis is very important for
      preventing neurologic damage. In this case report, we present the case of a 10
      year-old boy with signs and symptoms of hypoglycemia and final diagnosis of
      insulinoma.

PMID- 28512590
TI  - Acute Bacterial Meningitis and Systemic Abscesses due to Streptococcus
      dysgalactiae subsp. equisimilis Infection.
AB  - Disseminated abscesses due to group G beta-hemolytic Streptococcus dysgalactiae
      were observed in a 57-year-old cirrhotic patient with the skin being the putative
      way of entry for the pathogen. S. dysgalactiae is a rare agent in human
      infections responsible for acute pyogenic meningitis. The mortality rate
      associated with S. dysgalactiae bacteraemia and meningitis may be as high as 50%,
      particularly in the presence of endocarditis or brain abscesses. In our patient,
      main sites of infections were meningitis and ventriculitis, spondylodiscitis,
      septic arthritis, and soft-tissue infections. In contrast, no endocarditis was
      evidenced. Cirrhosis-related immune suppression was considered as a
      pathophysiological cofactor for the condition. Fortunately, clinical status
      improved after long-term (3 months) antimicrobial therapy.

PMID- 28512593
TI  - Electrochemical Determination of Caffeine Content in Ethiopian Coffee Samples
      Using Lignin Modified Glassy Carbon Electrode.
AB  - Lignin film was deposited at the surface of glassy carbon electrode
      potentiostatically. In contrast to the unmodified glassy carbon electrode, an
      oxidative peak with an improved current and overpotential for caffeine at
      modified electrode showed catalytic activity of the modifier towards oxidation of
      caffeine. Linear dependence of peak current on caffeine concentration in the
      range 6 * 10-6 to 100 * 10-6 mol L-1 with determination coefficient and method
      detection limit (LoD = 3 s/slope) of 0.99925 and 8.37 * 10-7 mol L-1,
      respectively, supplemented by recovery results of 93.79-102.17% validated the
      developed method. An attempt was made to determine the caffeine content of
      aqueous coffee extracts of Ethiopian coffees grown in four coffee cultivating
      localities (Wonbera, Wolega, Finoteselam, and Zegie) and hence to evaluate the
      correlation between users preference and caffeine content. In agreement with
      reported works, caffeine contents (w/w%) of 0.164 in Wonbera coffee; 0.134 in
      Wolega coffee; 0.097 in Finoteselam coffee; and 0.089 in Zegie coffee were
      detected confirming the applicability of the developed method for determination
      of caffeine in a complex matrix environment. The result indicated that users'
      highest preference for Wonbera and least preference for Zegie cultivated coffees
      are in agreement with the caffeine content.

PMID- 28512592
TI  - The Relationship between Body Mass Index and the Severity of Coronary Artery
      Disease in Patients Referred for Coronary Angiography.
AB  - Background and Aim. Obesity is associated with an increased risk of
      cardiovascular disease and may be associated with more severe coronary artery
      disease (CAD); however, the relationship between body mass index [BMI (kg/m2)]
      and CAD severity is uncertain and debatable. The aim of this study was to examine
      the relationship between BMI and angiographic severity of CAD. Methods. Duke
      Jeopardy Score (DJS), a prognostic tool predictive of 1-year mortality in CAD,
      was assigned to angiographic data of patients >=18 years of age (N = 8,079).
      Patients were grouped into 3 BMI categories: normal (18.5-24.9 kg/m2), overweight
      (25.0-29.9 kg/m2), and obese (>=30 kg/m2); and multivariable adjusted hazard
      ratios for 1-year all-cause and cardiac-specific mortality were calculated.
      Results. Cardiac risk factor prevalence (e.g., diabetes, hypertension, and
      hyperlipidemia) significantly increased with increasing BMI. Unadjusted all-cause
      and cardiac-specific 1-year mortality tended to rise with incremental increases
      in DJS, with the exception of DJS 6 (p < 0.001). After adjusting for potential
      confounders, no significant association of BMI and all-cause (HR 0.70, 95% CI .48
      1.02) or cardiac-specific (HR 1.11, 95% CI .64-1.92) mortality was found.
      Conclusions. This study failed to detect an association of BMI with 1-year all
      cause or cardiac-specific mortality after adjustment for potential confounding
      variables.

PMID- 28512594
TI  - Rapid Determination of Six Low Molecular Carbonyl Compounds in Tobacco Smoke by
      the APCI-MS/MS Coupled to Data Mining.
AB  - A simple method was established for the rapid determination of low molecular
      carbonyl compounds by the combination of atmospheric pressure chemical ionization
      tandem mass spectrometry (APCI-MS/MS) and data mining. The ionization was carried
      out in positive mode, and six low molecular carbonyl compounds of acrolein,
      acetone, propionaldehyde, crotonaldehyde, butanone, and butyraldehyde were
      analyzed by both full scan mode and daughter scan mode. To overcome the
      quantitative difficulties from isomer of acetone/propionaldehyde and
      butanone/butyraldehyde, the quantitation procedure was performed with the
      characteristic ion of [CH3O]+ under CID energy of 5 and 15 eV. Subsequently, the
      established method was successfully applied to analysis of six low molecular
      carbonyl compounds in tobacco smoke with analytical period less than four
      minutes. The contents of acrolein, acetone, propionaldehyde, crotonaldehyde,
      butanone, and butyraldehyde for a cigarette were about 63 +/- 5.8, 325 +/- 82, 55
      +/- 9.7, 11 +/- 1.4, 67 +/- 5.9, and 12 +/- 1.8 MUg/cig, respectively. The
      experimental results indicated that the established method had the potential
      application in rapid determination of low molecular carbonyl compounds.

PMID- 28512596
TI  - In vitro screening for protein tyrosine phosphatase 1B and dipeptidyl peptidase
      IV inhibitors from selected Nigerian medicinal plants.
AB  - BACKGROUND/AIM: Protein tyrosine phosphatase 1B (PTP 1B) and dipeptidyl peptidase
      IV (DPP IV) have been identified as one of the drug targets for the treatment of
      Type-2 diabetes. This study was designed to screen for PTP 1B and DPP-IV
      inhibitors from some Nigerian medicinal plants. MATERIALS AND METHODS: PTP 1B and
      DPP-IV drug discovery kits from Enzo Life Sciences were used to investigate in
      vitro inhibitory effect of crude methanolic extract of 10 plants; Mangifera
      indica, Moringa oleifera, Acacia nilotica, Arachis hypogaea, Senna nigricans,
      Azadirachta indica, Calotropis procera, Leptadenia hastata, Ziziphus mauritiana,
      and Solanum incanum. RESULTS: The results indicated PTP IB inhibition by S.
      nigricans (68.2 +/- 2.29%), A. indica (67.4 +/- 2.80%), A. hypogaea (57.2 +/-
      2.50%), A. nilotica (55.1 +/- 2.19%), and M. oleifera (41.2 +/- 1.87%) were
      significantly (P < 0.05) higher as compared with standard inhibitor, sumarin
      while that of L. hastata (18.1 +/- 2.00%) was significantly lower as compared
      with sumarin. The PTB 1B inhibition by M. indica (31.5 +/- 1.90%) was not
      significantly (P > 0.05) different from that of sumarin. The DPP-IV inhibition by
      S. incanum (68.1 +/- 2.71%) was significantly higher as compared with a known
      inhibitor, P32/98. S. nigrican (57.0+/-1.91%), Z. mauritiana (56.6+/-2.01%), A.
      hypogaea (51.0+/-1.30%), M. indica (44.6 +/- 2.40%), C. procera (36.2 +/- 2.00%),
      A. nilotica (35.4 +/- 2.10%), and A. indica (33.6 +/- 1.50%) show significantly
      (P < 0.05) lower inhibitions toward DPP-IV. CONCLUSION: The work demonstrated
      that these plant materials could serve as sources of lead compounds in the
      development of anti-diabetic agent(s) targeting PTP 1B and/or DPP-IV.

PMID- 28512595
TI  - Reassessment of the polar fraction of Stachys alopecuros (L.) Benth. subsp.
      divulsa (Ten.) Grande (Lamiaceae) from the Monti Sibillini National Park: A
      potential source of bioactive compounds.
AB  - BACKGROUND: The phytochemical analysis of Stachys alopecuros subsp. divulsa, an
      endemic Italian species, has been recently reported and has showed the presence
      of 8-O-acetylharpagide (2), harpagide (3), allobetonicoside (4), and 4c-O
      galactopyranosyl-teuhircoside (5). In this paper, an in deep study of its
      glycosidic fraction with the aim to widen the knowledge on its secondary
      metabolites content is reported. MATERIALS AND METHODS: Chromatographic
      techniques were used for the isolation of constituents while spectroscopic and
      spectrometric techniques were applied for the structures elucidation. RESULTS:
      Besides the known constituents, all of them reconfirmed, ajugoside (1), reptoside
      (6) and 6-O-acetyl-ajugol (7) were also identified among the iridoids while the
      phenolic components resulted to be chlorogenic acid (8), b-arbutin (9),
      verbascoside (10), and stachysoside A (11), instead. CONCLUSION: The iridoid
      pattern of S. alopecuros subsp. divulsa has been expanded with the identification
      of not previously reported compounds as well as for the phenolic fraction. Except
      for the reconfirmed verbascoside (10), the other phenolic compounds were
      recognized for the first time in the studied species. The complete NMR assignment
      of compound (1) by means of bidimensional techniques is reported, and both the
      chemotaxonomic and pharmacological relevance of the isolated compounds is largely
      discussed.

PMID- 28512597
TI  - Documentation of ethnomedicinal information and antimicrobial validation of
      Thespesia populnea used by Yanadi tribe of Ganugapenta village, Chittoor
      district, Andhra Pradesh, India.
AB  - AIM: This study aimed to document the traditional knowledge of medicinal plants
      and antimicrobial validation of Thespesia populnea used by Yanadi tribe of
      Chittoor district, Andhra Pradesh, India. MATERIALS AND METHODS: The study was
      mainly focused on documentation of medicinal plants used by Yanadi tribe to treat
      different diseases with a standard questionnaire. These plants were cross-checked
      in Dr. Dukes Database and available literature to know the significance of this
      tribe on medicinal knowledge. Among the documented plants, T. populnea was
      selected for antimicrobial activity with disc diffusion assay. RESULTS: Among the
      documented medicinal plants, herbs were the most utilized plants, followed by
      leaf part of the plants; paste form of medicinal preparation was the dominant one
      among the mode of preparations and oral administration was generally followed by
      this tribe. When checked these plants in Dr. Duke's Phytochemical and
      Ethnobotanical Database most of the medicinal plants were matched at least one
      medicinal use and most of them were correlated with existing literature. In
      antimicrobial activity, the microbial pathogens Klebsiella pneumonia among
      bacteria and Rhizopus arrhizus among fungi were most susceptible to methanol
      extract of T. populnea. CONCLUSION: From this study, we conclude that the
      preparation and dosage of the medicines by Yanadi tribe of this area is unique
      and the correlation of medicinal data with Duke's Database and existing
      literature reveals high medicinal significance of claimed data of this tribe and
      potential inhibitory activity of T. populnea could be studied further to isolate
      effective antimicrobial agents.

PMID- 28512598
TI  - Phytochemical screening and study of antioxidant, antimicrobial, antidiabetic,
      anti-inflammatory and analgesic activities of extracts from stem wood of
      Pterocarpus marsupium Roxburgh.
AB  - AIMS: The main aims of the study were to evaluate the phytochemical constituents
      and to study the antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and
      analgesic activities of extracts from stem wood of Pterocarpus marsupium.
      MATERIALS AND METHODS: Ethanol, acetone and isopropyl alcohol (IPA) (1:1)
      extracts of stem wood of P. marsupium were subjected to phytochemical screening
      and analysis of biological activities from August 2015 to January 2016. The
      antioxidant assay was carried out using 2, 2-diphenyl-1-picrylhydrazyl scavenging
      method, antimicrobial activity testing by cup diffusion method, antidiabetic test
      evaluation by oral glucose tolerance test in mice, anti-inflammatory effect was
      evaluated by hind paw edema method in mice and analgesic test evaluation by a
      chemical writhing method in mice. RESULTS: The results of the study revealed that
      P. marsupium is a source of various phytoconstituents such as alkaloids,
      glycosides, saponins, tannins, proteins, carbohydrates, cardiac glycosides,
      flavonoids, and terpenoids. Both the acetone and IPA extract as well as the
      ethanol extract of stem wood of P. marsupium exhibited a dose-dependent
      antioxidant activity. Acetone and IPA extract showed antibacterial activity
      against Gram-positive bacteria, while the ethanolic extract was found to possess
      antidiabetic activity. The antidiabetic activity of the extract was found to be
      time and dose-dependent. Similarly, the acetone and IPA extract was found to have
      anti-inflammatory activity, which was also time and dose-dependent. Furthermore,
      the ethanolic extract showed analgesic activity, which was dose-dependent. The
      ethanolic extract was found to be nontoxic. CONCLUSIONS: Thus, this study laid
      sufficient background for the further research on extracts from stem wood of P.
      marsupium for identification, subsequent purification and isolation of compounds
      having antibacterial, antidiabetic, anti-inflammatory, and analgesic activities.

PMID- 28512599
TI  - Effect of Trichilia monadelpha (Meliaceae) extracts on bone histomorphology in
      complete Freund's adjuvant-induced arthritis.
AB  - AIM: This study aimed to assess the effect of petroleum ether extract (PEE),
      ethyl acetate extract (EthE), and ethanol extract (EAE) of Trichilia monadelpha
      stem bark on bone histomorphology in arthritis. METHODS: Percentage inhibition of
      edema and arthritic scores in complete Freund's adjuvant-induced (0.1 ml of 5
      mg/ml1 of heat-killed Mycobacterium tuberculosis in paraffin oil-injected
      subplantar into the right hind paw) arthritic Sprague-Dawley rats treated with
      PEE, EthE, or EAE (10,30, and 100 mg/kg1, respectively), dexamethasone (0.3-3.0
      mg/kg1), or methotrexate (0.1-1.0 mg/kg1) over a 28-day period were estimated.
      Rat paws were radiographed and scored. Body weights were taken and paw tissues
      were harvested for histopathological studies. RESULTS: The extracts significantly
      (P <= 0.01-0.0001) and dose dependently reduced the polyarthritic phase of
      arthritis. EAE and PEE significantly (P <= 0.01-0.0001) minimized edema spread
      from acute arthritic phase (days 0-10) to polyarthritic phase (days 10-28). EthE
      improved which deteriorated body weight in arthritis. All extracts significantly
      (P <= 0.05-0.01) improved arthritic score; reducing erythema, swelling and joint
      rigidity, and also significantly (P <= 0.05-0.01) reduced hyperplasia, pannus
      formation, and exudation of inflammatory cells into synovial spaces. CONCLUSION:
      The stem bark extracts of T. monadelpha reduce bone tissue damage and resorption
      associated with adjuvant-induced arthritis, hence could be useful in managing
      arthritis in humans.

PMID- 28512600
TI  - A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae)
      on the antibacterial activity of selected antibiotics and cell membrane
      permeability.
AB  - AIM/BACKGROUNDS: Artocarpanone isolated from Artocarpus heterophyllus L.
      (Moraceae) exhibits antibacterial activity. The present study investigated
      synergistic activity between artocarpanone and tetracycline, ampicillin, and
      norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus
      (MRSA), Pseudomonas aeruginosa, and Escherichia coli. MATERIALS AND METHODS: A
      broth microdilution method was used for evaluating antibacterial susceptibility.
      Synergistic effects were identified using a checkerboard method, and a bacterial
      cell membrane disruption was investigated by assay of released 260 nm absorbing
      materials following bacteriolysis. RESULTS AND DISCUSSION: Artocarpanone
      exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum
      inhibitory concentrations values of 125 and 500 MUg/mL, respectively. However,
      the compound showed strong antibacterial activity against E. coli (7.8 MUg/mL).
      The interaction between artocarpanone and all tested antibiotics revealed
      indifference and additive effects against P. aeruginosa and E. coli (fractional
      inhibitory concentration index [FICI] values of 0.75-1.25). The combination of
      artocarpanone (31.2 MUg/mL) and norfloxacin (3.9 MUg/mL) resulted in synergistic
      antibacterial activity against MRSA, with an FICI of 0.28, while the interaction
      between artocarpanone and tetracycline, and ampicillin showed an additive effect,
      with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone
      had a synergistic effect on the antibacterial activity of norfloxacin. In
      addition, the combination of artocarpanone and norfloxacin altered the membrane
      permeability of MRSA. CONCLUSION: These findings suggest that artocarpanone may
      be used to enhance the antibacterial activity of norfloxacin against MRSA.

PMID- 28512601
TI  - Anti-nociceptive and anti-inflammatory potentials of Vernoniaamygdalina leaf
      extract via reductions of leucocyte migration and lipid peroxidation.
AB  - BACKGROUND: Vernonia amygdalina is well known as a medicinal plant in folk
      medicine as antidiabetic, anthelmintic, antimalarial, laxative/purgative, and
      expectorant among others. AIM: This study was conducted to investigate the
      antinociceptive and anti-inflammatory effects of V. amygdalina. MATERIALS AND
      METHODS: Methanol extract of V. amygdalina leaf (MEVA) was evaluated for
      antinociceptive effect and possible mechanisms of action in the presence of
      naloxone (1 mg/kg), atropine (2 mg/kg), and prazosin (1 mg/kg) using acetic acid
      writhing test in mice. The anti-inflammatory effect was evaluated in carrageenan
      hind paw edema and carrageenan air pouch models. Protein concentration,
      malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) assays
      were carried out for its antioxidative activities in inflammation. Hematoxylin
      and eosin staining was used to assess the level of inflammation. RESULTS: From
      the acetic acid writhing test results, MEVA (50,100 mg/kg) showed significant
      antinociceptive effect. Naloxone, atropine and prazosin did not significantly
      reverse the antinociceptive effect of MEVA (50 mg/kg). MEVA (50, 100, and 200
      mg/kg) showed dose-dependent inhibition of edema (41.4, 63.0, and 68.6%) at 4 h
      post-carrageenan injection. In the carrageenan air pouch model, MEVA (200 mg/kg)
      significantly (P < 0.05) reduced infiltrating leukocytes, protein concentration
      and MDA levels, while GSH and SOD were unaffected. The histological study showed
      a reduction in the infiltration of inflammatory cells in MEVA-treated groups.
      CONCLUSION: V. amygdalina showed antinociceptive activity and anti-inflammatory
      effect via reductions of leukocyte migration and lipid peroxidation.

PMID- 28512603
TI  - Bactericidal activity of herbal volatile oil extracts against multidrug-resistant
      Acinetobacter baumannii.
AB  - AIM: The aim of the study is to investigate the antibacterial activity of 10
      volatile oils extracted from medicinal plants, including galangal (Alpinia
      galanga Linn.), ginger (Zingiber officinale), plai (Zingiber cassumunar Roxb.),
      lime (Citrus aurantifolia), kaffir lime (Citrus hystrix DC.), sweet basil (Ocimum
      basilicum Linn.), tree basil (Ocimum gratissimum), lemongrass (Cymbopogon
      citratus DC.), clove (Syzygium aromaticum), and cinnamon (Cinnamomum verum)
      against four standard strains of Staphylococcus aureus, Escherichia coli,
      Pseudomonas aeruginosa, Acinetobacter baumannii, and 30 clinical isolates of
      multidrug-resistant A. baumannii (MDR-A. baumannii). MATERIALS AND METHODS: Agar
      diffusion, minimum inhibitory concentration, and minimum bactericidal
      concentration (MBC) were employed for the determination of bactericidal activity
      of water distilled medicinal plants. Tea tree oil (Melaleuca alternifolia) was
      used as positive control in this study. RESULTS: The results indicated the
      volatile oil extracted from cinnamon exhibited potent antibacterial activity
      against the most common human pathogens, S. aureus, E. coli, P. aeruginosa, and
      A. baumannii. Most of volatile oil extracts were less effective against non
      fermentative bacteria, P. aeruginosa. In addition, volatile oil extracted from
      cinnamon, clove, and tree basil possessed potent bactericidal activity against
      MDR-A. baumannii with MBC90 of 0.5, 1, and 2 mg/mL, respectively. CONCLUSIONS:
      The volatile oil extracts would be useful as alternative natural product for the
      treatment of the most common human pathogens and MDR-A. baumannii infections.

PMID- 28512604
TI  - Traditional dentistry knowledge among Serbs in several Balkan countries.
AB  - BACKGROUND/AIM: There are still unrevealed treasures of traditional dental
      medicine, that is, the reason to investigate and present various ways in
      treatment of oral and orofacial tissues, as well as magic and religious elements
      involved in representative areas among Serbs. MATERIALS AND METHODS: Information
      was collected from the elderly non-professional folk dentists and herbalists with
      the additional help of local physicians and dentists that was done through
      questionnaire and personal interviews. RESULTS: Classified and prepared material
      consists of total 1038 inquiry sheets. The 41 data were averagely obtained by
      inquiry form, i.e. 41,984 information for the whole research. The most voluminous
      was the group of 64 recipes, including 39 for gums diseases and 25 for toothache,
      while only seven ones were mentioned for magic way of treatment. Among them, 18
      prescriptions were of nonherbal origin. The study revealed 84 herbal original
      prescriptions, including 67 plant species (29 families) including local name,
      synonyms, and preparation mode. Traditional healers used predominantly herbal
      recipes to treat painful tooth, gum disease, blisters - herpetic ulcers/lips and
      mouth/, stomatitis/painful mouth, ptyalismus/, maxillary sinusitis, bad breath,
      teeth cleaning and bleaching. Very few methods of treatment appeared as
      inadequate (magical practice), whereas majority were noted as beneficial ones
      (herbal medicine). Still many people in distant nonurban areas use various plant
      recipes, especially as the first aid in oral disease healing. CONCLUSIONS: The
      significance of plants obtained from unpolluted areas, whose active ingredients
      have not yet been used in dental pharmaceutics, should be further investigated in
      the future.

PMID- 28512602
TI  - Bio-efficacy of medicinal plants used for the management of diabetes mellitus in
      Gabon: An ethnopharmacological approach.
AB  - BACKGROUND/AIM: People suffering of diabetes increased significantly worldwide.
      Population, in Sub-Saharan Africa and mainly in Gabon, rely on medicinal plants
      to manage diabetes, as well in rural as in urban areas. This study aimed to
      survey a wide range of Gabonese plants for their antidiabetic activity. MATERIALS
      AND METHODS: This study focused on the identification of medicinal plants used in
      the local treatment of diabetes mellitus. Ethnobotanical investigations were
      carried out in rural and urban areas of three provinces of Gabon using a semi
      structured interview. RESULTS: About 50 plant species belonging to 31 families
      and 50 genera were recorded, a majority of which have been documented previously
      to have medicinal properties. Most have documented antidiabetic properties with
      characterized therapeutic chemical compounds. Of the plant parts used for
      treatment, stem barks were employed most frequently (50%), followed by leaves
      (26%); the remaining 24% comprised roots, fibers, fruit, bulbs, flowers, rhizom,
      skin, and stem. Regarding the mode of preparation, decoction was the most widely
      used (58%), followed by maceration (18%) and infusion (14%). Almost all the plant
      products were administered orally (98%). CONCLUSIONS: Taken in concert, this
      study highlights the possibility of exploiting traditional knowledge of specific
      medicinal plants for the inexpensive treatment and management of diabetes.

PMID- 28512605
TI  - Toxicity status and antiulcerative potential of Sansevieria trifasciata leaf
      extract in Wistar rats.
AB  - AIMS: The lethal dose 50% (LD50) and antiulcerative potentials of Sansevieria
      trifasciata (ST) leaf extract were investigated. MATERIALS AND METHODS: LD50 was
      determined through two routes of administration (intraperitoneal [i.p] and oral
      [p.o]) using the method of Lorke. The antiulcerative activity was evaluated in
      indomethacin-induced ulcer model (40 mg/kg body weight [BW], i.p, single dose)
      against a reference drug, cimetidine (100 mg/kg BW, p.o). ST was assessed at two
      different doses (200 and 400 mg/kg BW, p.o). Treatments were done twice daily at
      8 h interval for 7 days before indomethacin administration. RESULTS: The i.p LD50
      was determined as 774.60 mg/kg BW and oral administration of the extract at
      18,000 mg/kg BW dosage did not cause any negative behavioral changes in the
      animals, and no mortality was recorded after 24 h of the experiment. ST-pre
      treated animals showed some improvement against indomethacin-induced ulceration.
      The extract curtailed indomethacin-induced reduction in gastric volume (36.1%),
      free acidity (55.3%), total acidity (35.6%) while minimizing the increase in pH
      by 13.3%. Moreover, the extract showed 17.92% and 14.96% ulcer protective ability
      at 200 and 400 mg/kg BW, respectively. The phytochemical analysis of ST extract
      revealed the presence of phytoconstituents such as glycosides, saponins,
      flavonoids, terpenoids, alkaloids, tannins, anthraquinone, and glycosides.
      CONCLUSIONS: ST apparently has a promising antiulcerative potential, and is safe
      for use in folk medicine. This valuable medicinal property is probably due to the
      array of important phytochemicals contained in the plant as observed in this
      study. However, a further study involving bioassay-guided identification of the
      main antiulcerative compound in ST is required to establish the use of the plant
      as a viable antiulcerative agent.

PMID- 28512606
TI  - Antimicrobial activity of Nigerian medicinal plants.
AB  - Antimicrobial resistance (AMR) is currently one of the major threats facing
      mankind. The emergence and rapid spread of multi- and pan-drug-resistant
      organisms (such as vancomycin-, methicillin-, extended-spectrum beta-lactam-,
      carbapenem- and colistin-resistant organisms) has put the world in a dilemma. The
      health and economic burden associated with AMR on a global scale are dreadful.
      Available antimicrobials have been misused and are almost ineffective with some
      of these drugs associated with dangerous side effects in some individuals.
      Development of new, effective, and safe antimicrobials is one of the ways by
      which AMR burden can be reduced. The rate at which microorganisms develop AMR
      mechanisms outpaces the rate at which new antimicrobials are being developed.
      Medicinal plants are potential sources of new antimicrobial molecules. There is
      renewed interest in antimicrobial activities of phytochemicals. Nigeria boasts of
      a huge heritage of medicinal plants and there is avalanche of researches that
      have been undertaken to screen antimicrobial activities of these plants.
      Scientific compilation of these studies could provide useful information on the
      antimicrobial properties of the plants. This information can be useful in the
      development of new antimicrobial drugs. This paper reviews antimicrobial
      researches that have been undertaken on Nigerian medicinal plants.

PMID- 23868168
TI  - An Algorithm for Calculating the Probability of Classes of Data Patterns on a
      Genealogy.
AB  - Felsenstein's pruning algorithm allows one to calculate the probability of any
      particular data pattern arising on a phylogeny given a model of character
      evolution. Here we present a similar dynamic programming algorithm. Our algorithm
      treats the tree and model as known. The algorithm makes it feasible to calculate
      the probability that a randomly selected character will be a member of a
      particular class of character patterns. Specifically, we are interested in
      binning patterns by the number of parsimony steps and the set of states observed
      at the tips of the tree. This algorithm was developed to expand the range of data
      set sizes that can be used with Waddell et al.'s marginal testing approach for
      assessing the adequacy of a model. The algorithms introduced can also be used in
      likelihood calculations which correct for ascertainment biases. For example,
      Lewis introduced an Mkv model which corrects for the lack of constant sites. The
      probability of a constant pattern arising can be calculated using the algorithm
      that we present, or by enumerating all possible constant patterns and calculating
      the probability of each one. Because the number of constant data patterns is
      small, both methods are efficient. However, elaborations of the Mkv model (such
      as those in Nylander et al) require calculating the probability of parsimony
      uninformative patterns arising. For large trees and characters with many possible
      character states, the number of possible parismony-uninformative patterns is
      immense. In these cases, the algorithms introduced here will be more efficient.
      The algorithm has been implemented in open source software written in C++.

PMID- 24678439
TI  - The Role of Veterans Affairs in Emergency Management: A Systematic Literature
      Review.
AB  - The Department of Veterans Affairs (VA) is a key player in emergency management
      for both veterans and civilians. Unfortunately, limited evidence-based research
      findings exist regarding the role and experience of VA during disasters. The
      present study is a systematic literature review of 41 published, peer-reviewed
      articles regarding VA and emergency management. Trained researchers utilized a
      data abstraction tool and conducted a qualitative content analysis. A description
      of article characteristics include methodology, phase of emergency management
      addressed in the research, and study design. Five topic categories emerged from
      the review including effects of disaster on mental health status and services
      use, effects of disaster on general health services use, patient tracking,
      evacuation, and disaster planning/preparation. Findings were used to generate
      suggestions for future research.

PMID- 24818064
TI  - A Prospective Study of the Outcome of Patients with Limb Trauma following the
      Haitian Earthquake in 2010 at One- and Two- Year (The SuTra2 Study).
AB  - Background Severe limb trauma is common in earthquake survivors. Overall medium
      term outcomes and patient-perceived outcomes are poorly documented. Methods and
      Findings The prospective study SuTra2 assessed the functional and socio-economic
      status of a cohort of patients undergoing surgery for limb injury resulting in
      amputation (A) or limb preservation (LP) one year and two years after the 2010
      Haiti earthquake. 305 patients [A: n=199 (65%), LP: n=106 (35%)] were evaluated.
      Their characteristics were: 57% female; mean age 31 years; 74% of principal
      injuries involved the lower limb; 46% of patients had an additional severe
      injury; 60% had fractures, of which two-thirds were compound or associated with
      severe soft tissue damage; 15% of amputations were traumatic. At 2 years, 51% of
      patients were satisfied with the functional outcome (A: 52%, LP: 49%, ns).
      Comparison with the 1-year status indicates a worsening of the perceived
      functional status, significantly more pronounced in amputees, and an increase in
      pain complaints, mainly in amputees (62% and 80% of pain in overall population at
      1- and 2-year respectively). Twenty eight percent (28%) of LP and 66% of A
      considered themselves as "cured". 100% of LP and 79% of A would have chosen a
      conservative approach if an amputation was medically avoidable. Two years after
      the earthquake, 23.5 % of patients were still living in a tent, 30% were working,
      and 25.5% needed ongoing surgical management. Conclusions Only half the patients
      with severe limb injuries, whether managed with amputation or limb preservation,
      deemed their functional status satisfactory at 2 years. The patients'
      perspective, clearly favors limb conservative management whenever possible.
      Prolonged care and rehabilitation are needed to optimize the outcome for
      earthquake survivors with limb injuries. Humanitarian respondents to catastrophes
      have professional and ethical obligations to provide optimal immediate care and
      ensure scrupulous attention to long-term management. Keywords Haiti earthquake,
      limb injury, two-year outcome, patients' perspective, amputation, limb salvage.

PMID- 28512610
TI  - Melanoma Is Skin Deep: A 3D Reconstruction Technique for Computerized Dermoscopic
      Skin Lesion Classification.
AB  - Melanoma mortality rates are the highest amongst skin cancer patients. Melanoma
      is life threating when it grows beyond the dermis of the skin. Hence, depth is an
      important factor to diagnose melanoma. This paper introduces a non-invasive
      computerized dermoscopy system that considers the estimated depth of skin lesions
      for diagnosis. A 3-D skin lesion reconstruction technique using the estimated
      depth obtained from regular dermoscopic images is presented. On basis of the 3-D
      reconstruction, depth and 3-D shape features are extracted. In addition to 3-D
      features, regular color, texture, and 2-D shape features are also extracted.
      Feature extraction is critical to achieve accurate results. Apart from melanoma,
      in-situ melanoma the proposed system is designed to diagnose basal cell
      carcinoma, blue nevus, dermatofibroma, haemangioma, seborrhoeic keratosis, and
      normal mole lesions. For experimental evaluations, the PH2, ISIC: Melanoma
      Project, and ATLAS dermoscopy data sets is considered. Different feature set
      combinations is considered and performance is evaluated. Significant performance
      improvement is reported the post inclusion of estimated depth and 3-D features.
      The good classification scores of sensitivity = 96%, specificity = 97% on PH2
      data set and sensitivity = 98%, specificity = 99% on the ATLAS data set is
      achieved. Experiments conducted to estimate tumor depth from 3-D lesion
      reconstruction is presented. Experimental results achieved prove that the
      proposed computerized dermoscopy system is efficient and can be used to diagnose
      varied skin lesion dermoscopy images.

PMID- 28512612
TI  - Review of Cranioplasty after Decompressive Craniectomy.
AB  - Cranioplasty is an in evitable operation conducted after decompressive
      craniectomy (DC). The primary goals of cranioplasty after DC are to protect the
      brain, achieve a natural appearance and prevent sinking skin flap syndrome (or
      syndrome of the trephined). Furthermore, restoring patients' functional outcome
      and supplementing external defects helps patients improve their self-esteem.
      Although early cranioplasty is preferred in recent year, optimal timing for
      cranioplasty remains a controversial topic. Autologous bone flaps are the most
      ideal substitute for cranioplasty. Complications associated with cranioplasty are
      also variable, however, post-surgical infection is most common. Many new
      materials and techniques for cranioplasty are introduced. Cost-benefit analysis
      of these new materials and techniques can result in different outcomes from
      different healthcare systems.

PMID- 28512611
TI  - Decompressive Craniectomy in Traumatic Brain Injury: A Review Article.
AB  - The importance of treating traumatic brain injury (TBI) is well known worldwide.
      Although many studies have been conducted in this topic, there is still much
      uncertainty about the effectiveness of surgical treatment in TBI. Recently, good
      randomized controlled trial (RCT) papers about the effectiveness of decompressive
      craniectomy (DC) in TBI has been published. In this article, we will review the
      overall contents of the DC (historical base, surgical technic, rationale,
      complications) and the results of the recently published RCT paper.

PMID- 28512613
TI  - Comparison of Complications Following Cranioplasty Using a Sterilized Autologous
      Bone Flap or Polymethyl Methacrylate.
AB  - OBJECTIVE: The aims of current study are to compare complications following
      cranioplasty (CP) using either sterilized autologous bone or polymethyl
      methacrylate (PMMA), and to identify the risk factors for two of the most common
      complications: bone flap resorption (BFR) and surgical site infection (SSI).
      METHODS: Between January 2004 and December 2013, 127 patients underwent CP and
      were followed at least 12 months. Variables, including sex, age, initial
      diagnosis, time interval between decompressive craniectomy (DC) and CP, operation
      time, size of bone flap, and presence of ventriculo-peritoneal shunt, were
      analyzed to identify the risk factors for BFR and SSI. RESULTS: A total of 97
      (76.4%) patients underwent CP using PMMA (Group I) and 30 (23.6%) underwent CP
      using autologous bone (Group II). SSI occurred in 8 (8.2%) patients in Group I,
      and in 2 (6.7%) in Group II; there was no statistically significant difference
      between the groups (p=1.00). No statistically significant risk factors for SSI
      were found in either group. In Group I, there was no reported case of BFR. In
      Group II patients, BFR developed in 18 (60.0%) patients at the time of CP (Type 1
      BFR), and at 12-month follow up (Type 2 BFR) in 4 (13.3%) patients. No
      statistically significant risk factors for BFR were found in Group II.
      CONCLUSION: CP using sterilized autologous bone result in a significant rate of
      BFR. PMMA, however, is a safe alloplastic material for CP, as it has low
      complication rate.

PMID- 28512614
TI  - Postoperative Contralateral Hematoma in Patient with Acute Traumatic Brain
      Injury.
AB  - OBJECTIVE: Head injury is a leading cause of death and disability in subjects who
      suffer a traumatic accident. Contralateral hematomas after surgery for traumatic
      brain injury are rare. However, an unrecognized, these hematomas can cause
      devastating results. We presented our experience of these patients and discussed
      diagnosis and management. METHODS: This study included 12 traumatic patients with
      acute traumatic brain injury who developed delayed contralateral hematoma after
      evacuation of an acute hematoma. Clinical and radiographic data was obtained
      through review of medical records and radiographs retrospectively. RESULTS: Ten
      males and two females were included in the study. Ten (83.3%) patients had severe
      head injury (Glasgow Coma Scale [GCS] score <8). Intraoperative brain swelling
      during removal of the traumatic subdural hematoma was noted in 10 (83.3%)
      patients. A skull fracture on the side contralateral to the acute hematoma was
      noted on computed tomography (CT) scans of nine (75%) patients. Three (33.3%)
      patients with severe head injury (GCS <8) died. Only (10%) one patient with a
      severe head injury had less severe disability. CONCLUSION: A postoperative CT
      scan is essential in patients with acute traumatic brain injury and a
      contralateral skull fracture or a low GCS score. Our results indicated that it is
      very important to evaluate this rare but potentially devastating complication.

PMID- 28512615
TI  - Delayed Infarction of Medullar and Cerebellum 3 Months after Vertebral Artery
      Injury with C1-2 Fracture: Case Report.
AB  - The clinical manifestations of vertebral artery (VA) injury (VAI) after cervical
      trauma range from asymptomatic to fatal cerebral infarction. Thrombotic occlusion
      and embolization to the distal arteries can cause cerebellar and brain stem
      infarction within days after trauma. We report a 64-year-old man who underwent
      arthrodesis surgery for C1 and C2 fractures. He had left VAI at the C2 transverse
      foramen site but was asymptomatic. The patient experiences brainstem and
      cerebellar infarction 3 months after injury to the VA, and we are here to discuss
      the treatment of VAI after cervical trauma.

PMID- 28512616
TI  - Surgical Management of Syringomyelia Associated with Spinal Adhesive
      Arachnoiditis, a Late Complication of Tuberculous Meningitis: A Case Report.
AB  - Syringomyelia associated with tuberculous meningitis is an extremely rare
      condition. Only a few studies have reported clinical experience with
      syringomyelia as a late complication of tuberculous meningitis. Twenty-six years
      after a tuberculous meningitis episode, a 44-year-old man presented with
      progressively worsening spastic paresis of the lower limbs and impaired urinary
      function for 2 years. Radiological examination revealed syringomyelia extending
      from the level of C2 to T9 and arachnoiditis with atrophy of the spinal cord
      between C2 and T3. We performed laminectomy from C7 to T1, dissected the
      arachnoid adhesion and placed a syringo-pleural shunt via keyhole myelotomy. One
      year after the operation, his neurological condition improved. The postoperative
      control magnetic resonance imaging revealed the correctly located shunt and
      significantly diminished syringomyelia cavities. We aim to discuss the mechanism
      of syrinx formation following tuberculous meningitis and to share our surgical
      therapeutic experience with this rare disease entity.

PMID- 28512617
TI  - Vertebral Artery Injury in C2-3 Epidural Schwannoma Resection: A Case Report and
      Literature Review.
AB  - The incidence of vertebral artery (VA) injury (VAI) in posterior approach tumor
      resection surgery is extremely rare, but it can lead to serious complication. In
      this case, a 57-year-old man underwent surgery for resection of the tumor
      involving left epidural space and neural foramen at C2-3 level. Iatrogenic VAI
      occurred suddenly during tumor resection procedure using pituitary forceps.
      Immediate local hemostasis and maintaining of perfusion for reducing the risk of
      posterior circulation ischemia were performed. Intraoperative angiogram of both
      VA and emergent trapping embolization were done as well. It may reduce the risk
      of immediate postop complication, and further delayed occurrence. The patient had
      no complication after VAI by appropriate intraoperative management. Preoperative
      angiographic work up and preparation of endovascular team cooperation are
      positively necessary as well as a warning for the VAI during cervical spine
      surgery.

PMID- 28512618
TI  - Incomplete Isolated C7 Root Injury Caused by Gunshot Wound: A Case Report.
AB  - Gunshot wounds to the spine cause severe neurological and/or internal organs
      damages. Although most of publications in the literature are realized on military
      injuries, increased civilian arming which raises civilian gunshot injuries is a
      new social danger causing serious health problems. In gunshot injuries to the
      spine; vertebral column, spinal cord and nerve roots are damaged with direct,
      indirect and transient cavitation related mechanisms. In this case report, we
      present 24 years old male patient who had severe pain and monoparesis in left
      upper extremity followed by gunshot injury to the spine with clinical,
      radiological and postoperative follow-up findings.

PMID- 28512619
TI  - Severe Retrolisthesis at the Adjacent Segment after Lumbar Fusion Combined with
      Dynamic Stabilization.
AB  - Lumbar fusion using the pedicle screw system is a popular operative procedure,
      with favorable clinical results and high fusion rates. However, the risk of
      adjacent segment disease after lumbar fusion is problematic. We report a
      complicated case of severe retrolisthesis at L3-4 level following dynamic
      interspinous process stabilization at L2-3 level and a fusion at L4-5 level. The
      radiological and clinical findings of this complication are discussed, and a
      review of the literature is presented.

PMID- 28512620
TI  - Adjacent Bilateral Stress Pedicle Fractures after Instrumented Lumbar Fusion: A
      Case Report.
AB  - Bilateral pedicle stress fractures are rare even in the elderly. Bilateral
      pedicle fractures are due to post-surgical complications at the level of fusion
      or stress related activities in most cases. The authors describe a unique case of
      adjacent L4 bilateral pedicle fractures, which developed 4 years after anterior
      lumbar interbody fusion with bone cement augmented screw fixation at the L5-S1
      level. As far as the authors' knowledge, no similar case has been previously
      reported in the literature. The pathophysiological mechanism of this rare entity
      is discussed with review of relevant literature.

PMID- 28512621
TI  - Spontaneous Acute Subdural Hemorrhage in a Patient with a Tick Borne Bunyavirus
      Induced Severe Fever with Thrombocytopenia Syndrome.
AB  - We report the first case of severe fever with thrombocytopenia syndrome (SFTS)
      and a spontaneous acute subdural hematoma (SDH) in Korea. A 79-year-old male
      presented with fever and thrombocytopenia. On the third day of hospitalization,
      his mental changed from drowsy to semi-coma. Brain computed tomography indicated
      an acute subdural hemorrhage on the right convexity. He was given early
      decompressive craniectomy, but did not survive. Real-time reverse transcription
      polymerase chain reaction analysis of a blood sample indicated the presence of
      SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage
      and SFTS. This case report describes our treatment of a patient with acute SDH
      and an infection from a tick-borne species of Bunyaviridae.

PMID- 28512622
TI  - Erratum: Risk Factor Analysis for the Recurrence of Chronic Subdural Hematoma: A
      Review of 368 Consecutive Surgical Cases.
AB  - [This corrects the article on p. 63 in vol. 11, PMID: 27169067.].

PMID- 28512623
TI  - Ca2+ Microdomains in T-Lymphocytes.
AB  - Early Ca2+ signaling is characterized by occurrence of Ca2+ microdomains formed
      by opening of single or clusters of Ca2+ channels, thereby initiating first
      signaling and subsequently activating global Ca2+ signaling mechanisms. However,
      only few data are available focusing on the first seconds and minutes of Ca2+
      microdomain formation and related signaling pathways in activated T-lymphocytes.
      In this review, we condense current knowledge on Ca2+ microdomain formation in T
      lymphocytes and early Ca2+ signaling, function of Ca2+ microdomains, and
      microdomain organization. Interestingly, considering the first seconds of T cell
      activation, a triphasic Ca2+ signal is becoming apparent: (i) initial Ca2+
      microdomains occurring in the first second of T cell activation, (ii)
      amplification of Ca2+ microdomains by recruitment of further channels in the next
      5-10 s, and (iii) a transition to global Ca2+ increase. Apparently, the second
      messenger nicotinic acid adenine dinucleotide phosphate is the first second
      messenger involved in initiation of Ca2+ microdomains. Ryanodine receptors type 1
      act as initial Ca2+ release channels in CD4+ T-lymphocytes. Regarding the
      temporal correlation of Ca2+ microdomains with other molecular events of T cell
      activation, T cell receptor-dependent microdomain organization of signaling
      molecules Grb2 and Src homology [SH2] domain-containing leukocyte protein of 65
      kDa was observed within the first 20 s. In addition, fast cytoskeletal changes
      are initiated. Furthermore, the involvement of additional Ca2+ channels and
      organelles, such as the Ca2+ buffering mitochondria, is discussed. Future
      research developments will comprise analysis of the causal relation between these
      temporally coordinated signaling events. Taken together, high-resolution Ca2+
      imaging techniques applied to T cell activation in the past years paved the way
      to detailed molecular understanding of initial Ca2+ signaling mechanisms in non
      excitable cells.

PMID- 28512624
TI  - The Close Interconnection between Mitochondrial Dynamics and Mitophagy in Cancer.
AB  - Recent decades have revealed the shape changes of mitochondria and their
      regulators to be main players in a plethora of physiological cell processes.
      Mitochondria are extremely dynamic organelles whose highly controlled
      morphological changes respond to specific and diverse pathophysiological needs.
      Thus, their qualitative control is crucial for the determination of cell function
      and fate. Moreover, ever-new metabolic changes, mainly attributable to
      mitochondrial (dys)functions, are strongly connected to cancer and its
      microenvironment. For this reason, the aspects controlling mitochondria activity
      and status are in the oncological spotlight. In this review, we elucidate the
      most intriguing discoveries related to two apparently independent but strictly
      interconnected processes crucial for the organelle functionality and fate,
      mitochondrial dynamics, and mitophagy. We will mostly focus on their metabolic
      interconnections and regulations that can causally foster a tumoral context.

PMID- 28512625
TI  - Using Murine Models to Investigate Tumor-Lymphoid Interactions: Spotlight on
      Chronic Lymphocytic Leukemia and Angioimmunoblastic T-Cell Lymphoma.
AB  - The role of the tumor microenvironment in leukemias and lymphomas is well
      established, yet the intricacies of how the malignant cells regulate and
      influence their non-malignant counterparts remain elusive. For example, chronic
      lymphocytic leukemia (CLL) is an expansion of malignant CD5+CD19+ B cells, yet
      the non-malignant T cells play just as large of a role in disease presentation
      and etiology. Herein, we review the dynamic tumor cell to lymphoid repertoire
      interactions found in two non-Hodgkin's lymphoma subtypes: CLL and
      angioimmunoblastic T-cell lymphoma. We aim to highlight the pivot work done in
      the murine models which recapitulate these diseases and explore the insights that
      can be gained from studying the immuno-oncological regulation of non-malignant
      lymphoid counterparts.

PMID- 28512626
TI  - Anti-Restriction Protein, KlcAHS, Promotes Dissemination of Carbapenem
      Resistance.
AB  - Carbapenemase-producing Klebsiella pneumoniae (KPC) has emerged and spread
      throughout the world. A retrospective analysis was performed on carbapenem
      resistant K. pneumoniae isolated at our teaching hospital during the period 2009
      2010, when the initial outbreak occurred. To determine the mechanism(s) that
      underlies the increased infectivity exhibited by KPC, Multilocus Sequence Typing
      (MLST) was conducted. A series of plasmids was also extracted, sequenced and
      analyzed. Concurrently, the complete sequences of blaKPC-2-harboring plasmids
      deposited in GenBank were summarized and aligned. The blaKPC-2 and KlcAHS genes
      in the carbapenem-resistant K. pneumoniae isolates were examined. E. coli
      strains, carrying different Type I Restriction and Modification (RM) systems,
      were selected to study the interaction between RM systems, anti-RM systems and
      horizontal gene transfer (HGT). The ST11 clone predominated among 102 carbapenem
      resistant K. pneumoniae isolates, all harbored the blaKPC-2 gene; 98% contained
      the KlcAHS gene. KlcAHS was one of the core genes in the backbone region of most
      blaKPC-2 carrying plasmids. Type I RM systems in the host bacteria reduced the
      rate of pHS10842 plasmid transformation by 30- to 40-fold. Presence of the anti
      restriction protein, KlcAHS, on the other hand, increased transformation
      efficiency by 3- to 6-fold. These results indicate that RM systems can
      significantly restrict HGT. In contrast, KlcAHS can disrupt the RM systems and
      promote HGT by transformation. These findings suggest that the anti-restriction
      protein, KlcAHS, represents a novel mechanism that facilitates the increased
      transfer of blaKPC-2 and KlcAHS -carrying plasmids among K. pneumoniae strains.

PMID- 28512627
TI  - Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a
      Systemic Immune Response-Note of Caution for In vivo Infection Experiments.
AB  - Whether mice are an appropriate model for S. aureus infection and vaccination
      studies is a matter of debate, because they are not considered as natural hosts
      of S. aureus. We previously identified a mouse-adapted S. aureus strain, which
      caused infections in laboratory mice. This raised the question whether laboratory
      mice are commonly colonized with S. aureus and whether this might impact on
      infection experiments. Publicly available health reports from commercial vendors
      revealed that S. aureus colonization is rather frequent, with rates as high as
      21% among specific-pathogen-free mice. In animal facilities, S. aureus was
      readily transmitted from parents to offspring, which became persistently
      colonized. Among 99 murine S. aureus isolates from Charles River Laboratories
      half belonged to the lineage CC88 (54.5%), followed by CC15, CC5, CC188, and CC8.
      A comparison of human and murine S. aureus isolates revealed features of host
      adaptation. In detail, murine strains lacked hlb-converting phages and
      superantigen-encoding mobile genetic elements, and were frequently ampicillin
      sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than
      human CC88 isolates. Importantly, S. aureus colonization clearly primed the
      murine immune system, inducing a systemic IgG response specific for numerous S.
      aureus proteins, including several vaccine candidates. Phospholipase C emerged as
      a promising test antigen for monitoring S. aureus colonization in laboratory
      mice. In conclusion, laboratory mice are natural hosts of S. aureus and
      therefore, could provide better infection models than previously assumed. Pre
      exposure to the bacteria is a possible confounder in S. aureus infection and
      vaccination studies and should be monitored.

PMID- 28512629
TI  - A Modified Behavior Risk Factor Surveillance System to Assess Diabetes Self
      management Behaviors and Diabetes Care in Monterrey Mexico: A Cross-sectional
      Study.
AB  - Type 2 diabetes mellitus (T2DM) is one of the leading causes of death from
      worldwide non-communicable diseases. The prevalence of diabetes in the Mexico
      (MX)-United States border states exceeds the national rate in both countries. The
      economic burden of diabetes, due to decreased productivity, disability, and
      medical costs, is staggering and increases significantly when T2DM-related
      complications occur. The purpose of this study was to use a modified behavioral
      risk factor surveillance system (BRFSS) to describe the T2DM self-management
      behaviors, diabetes care, and health perception of a convenience sample of adults
      with T2DM in Monterrey, MX. This cross-sectional study design, with convenience
      sampling, was conducted with a convenience sample (n = 351) of adults in the
      metropolitan area of Monterrey, MX who self-reported a diagnosis of T2DM.
      Potential participants were recruited from local supermarkets. Twenty-six
      diabetes and health-related items were selected from the BRFSS and administered
      in face-to-face interviews by trained data collectors. Data analysis was
      conducted using descriptive statistics. The mean age was 47 years, and the mean
      length of time with T2DM was 12 years. The majority was taking oral medication
      and 34% required insulin. Daily self-monitoring of feet was performed by 56% of
      the participants; however, only 8.8% engaged in blood glucose self-monitoring.
      The mean number of health-care provider visits was 9.09 per year, and glycated
      hemoglobin level (HbA1c) was assessed 2.6 times per year. Finally, only 40.5% of
      the participants recalled having a dilated eye exam. We conclude the modified
      BRFSS survey administered in a face-to-face interview format is an appropriate
      tool for assessing engagement in T2DM self-management behaviors, diabetes care,
      and health perception. Extension of the use of this survey in a more rigorous
      design with a larger scale survey is encouraged.

PMID- 28512628
TI  - Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections,
      and B Lymphopenia: A Novel Variant of WHIM Syndrome?
AB  - WHIM syndrome is a condition in which affected persons have chronic peripheral
      neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus
      infection, and myelokathexis. Myelokathexis refers to the retention of mature
      neutrophils in the bone marrow (BM), which accounts for degenerative changes and
      hypersegmentation. Most patients present heterozygous autosomal dominant
      mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4
      signaling impairs the receptor downregulation causing hyperactivation (gain-of
      function) that affects BM homing for myelopoiesis and lymphopoiesis and the
      release of neutrophils in the bloodstream. We report the case of a 26-year-old
      female with severe foot and hand cutaneous warts since childhood, recalcitrant
      genital condylomatas, bacterial infections, and intraepithelial cervical
      neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high and low
      risk types. HIV testing was negative. Not only CXCR4 but also GATA2, NEMO, and
      CD40L gene mutations were excluded. BM smears revealed, in the presence of a
      normal cellularity, hyperplasia of myeloid cells (MPO positive) and karyorrhexis,
      especially in neutrophils and eosinophils. Of note, neutrophils with altered
      lobation of nuclei connected by long thin chromatin filaments were observed. Our
      patient presented a clinical and histological picture reminiscent of WHIM in the
      presence of normal peripheral neutrophil counts and wild-type CXCR4 gene.
      Although the BM did not reveal a classical pattern of myelokathexis, the
      observation of consistent signs of neutrophil dysplasia has fuelled the
      hypothesis of a novel WHIM variant or a novel immunodeficiency. We speculate that
      abnormalities that affect CXCR4/CXCL12 pair, including GRK levels or activity,
      might be responsible for this WHIM-like disorder.

PMID- 28512630
TI  - Hand Grasping Synergies As Biometrics.
AB  - Recently, the need for more secure identity verification systems has driven
      researchers to explore other sources of biometrics. This includes iris patterns,
      palm print, hand geometry, facial recognition, and movement patterns (hand
      motion, gait, and eye movements). Identity verification systems may benefit from
      the complexity of human movement that integrates multiple levels of control
      (neural, muscular, and kinematic). Using principal component analysis, we
      extracted spatiotemporal hand synergies (movement synergies) from an object
      grasping dataset to explore their use as a potential biometric. These movement
      synergies are in the form of joint angular velocity profiles of 10 joints. We
      explored the effect of joint type, digit, number of objects, and grasp type. In
      its best configuration, movement synergies achieved an equal error rate of 8.19%.
      While movement synergies can be integrated into an identity verification system
      with motion capture ability, we also explored a camera-ready version of hand
      synergies-postural synergies. In this proof of concept system, postural synergies
      performed well, but only when specific postures were chosen. Based on these
      results, hand synergies show promise as a potential biometric that can be
      combined with other hand-based biometrics for improved security.

PMID- 28512633
TI  - An Ambulatory Electroencephalography System for Freely Moving Horses: An
      Innovating Approach.
AB  - Electroencephalography (EEG) that has been extensively studied in humans presents
      also a large interest for studies on animal brain processes. However, since the
      quality of the recordings is altered by muscular activity, most EEG recordings on
      animals are obtained using invasive methods with deeply implanted electrodes.
      This requires anesthesia and can thus only be used in laboratory or clinical
      settings. As EEG is a very useful tool both for detecting brain alterations due
      to diseases or accidents and to evaluate the arousal and attentional state of the
      animal, it seemed crucial to develop a tool that would make such recordings
      possible in the horse's home environment, with a freely moving horse. Such a tool
      should neither be invasive nor cause discomforts to the horse as the usual other
      practice which consists, after shaving the zone, in gluing the electrodes to the
      skin. To fulfill these requirements, we developed a novel EEG headset adapted to
      the horse's head that allows an easy and fast positioning of the electrodes and
      that can be used in the home environment on a freely moving horse. In this study,
      we show that this EEG headset allows to obtain reliable recordings, and we
      propose an original evaluation of an animal's "EEG profile" that allows
      comparisons between individuals and situations. This EEG headset opens new
      possibilities of investigation on horse cognition, and it can also become a
      useful tool for veterinarians to evaluate cerebral disorders or check the
      anesthesia level during a surgery.

PMID- 28512631
TI  - Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori
      Infection.
AB  - Gastric cancer is a world health problem and depicts the fourth leading mortality
      cause from malignancy in Mexico. Causation of gastric cancer is not only due to
      the combined effects of environmental factors and genetic variants. Recent
      molecular studies have transgressed a number of genes involved in gastric
      carcinogenesis. The aim of this review is to understand the recent basics of gene
      expression in the development of the process of gastric carcinogenesis. Genetic
      variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved
      in mediating inflammation have been associated with the development of gastric
      carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, beta
      catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha,
      GSK3beta, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX
      2) have been studied in association with oncogenic activation or inactivation of
      tumor suppressor genes. All these mechanisms have been investigated to elucidate
      the process of gastric carcinogenesis, as well as their potential use as
      biomarkers and/or molecular targets to treatment of disease.

PMID- 28512632
TI  - Understanding Interleukin 33 and Its Roles in Eosinophil Development.
AB  - Over the last decade, significant interest in the contribution of three
      "epithelial-derived cytokines," such as thymic stromal lymphopoietin, interleukin
      25, and interleukin 33 (IL-33), has developed. These cytokines have been strongly
      linked to the early events that occur during allergen exposures and how they
      contribute to the subsequent type 2 immune response. Of these three cytokines, IL
      33 has proven particularly interesting because of the strong associations found
      between both it and its receptor, ST2, in several genome-wide association studies
      of allergic diseases. Further work has demonstrated clear mechanisms through
      which this cytokine might orchestrate allergic inflammation, including activation
      of several key effector cells that possess high ST2 levels, including mast cells,
      basophils, innate lymphoid cells, and eosinophils. Despite this, controversies
      surrounding IL-33 seem to suggest the biology of this cytokine might not be as
      simple as current dogmas suggest including: the relevant cellular sources of IL
      33, with significant evidence for inducible expression in some hematopoietic
      cells; the mechanistic contributions of nuclear localization vs secretion;
      secretion and processing mechanisms; and the biological consequences of IL-33
      exposure on different cell types. In this review, we will address the evidence
      for IL-33 and ST2 regulation over eosinophils and how this may contribute to
      allergic diseases. In particular, we focus on the accumulating evidence for a
      role of IL-33 in regulating hematopoiesis and how this relates to eosinophils as
      well as how this may provide new concepts for how the progression of allergy is
      regulated.

PMID- 28512634
TI  - User experience analysis of e-TB Manager, a nationwide electronic tuberculosis
      recording and reporting system in Ukraine.
AB  - Ukraine has successfully implemented e-TB Manager nationwide as its mandatory
      national tuberculosis registry after first introducing it in 2009. Our objective
      was to perform an end-of-programme evaluation after formal handover of the
      registry administration to Ukraine's Centre for Disease Control in 2015. We
      conducted a nationwide, cross-sectional, anonymous, 18-point user experience
      survey, and stratified the registry's transaction statistics to demonstrate
      usability. Contrary to initial implementation experience, older users (aged >50
      years), often with limited or no computer proficiency prior to using the
      registry, had significantly better user experience scores for at least six of the
      12 measures compared to younger users (aged 18-29 years). Using the registry for
      >3 years was associated with significantly higher scores for having capacity,
      adequacy of training received and satisfaction with the registry. Of the 5.9
      million transactions over a 4-year period, nine out of 24 oblasts (regions) and
      Kiev city accounted for 62.5% of all transactions, and corresponded to 59% of
      Ukraine's tuberculosis burden. There were 437 unique active users in 486 rayons
      (districts) of Ukraine, demonstrating extensive reach. Our key findings
      complement the World Health Organization and European Respiratory Society's
      agenda for action on digital health to help implement the End TB Strategy.

PMID- 28512635
TI  - Drug Susceptibility of 33 Reference Strains of Slowly Growing Mycobacteria to 19
      Antimicrobial Agents.
AB  - Objectives. Slowly growing mycobacteria (SGM) are prevalent worldwide and cause
      an extensive spectrum of diseases. Methods. In this study, the antimicrobial
      susceptibility of 33 reference strains of SGM to 19 antimicrobial agents was
      tested using a modified microdilution method. Results. Cefmetazole (32/33) and
      azithromycin (32/33) exhibited the highest antimicrobial activity, and dapsone
      (9/33) exhibited the lowest activity against the tested strains. Cefoxitin
      (30/33), cefoperazone (28/33), and cefepime (28/33) were effective against a high
      proportion of strains, and macrolides were also highly effective as well as
      offering the benefit of convenient oral administration to patients. Linezolid
      (27/33), meropenem (26/33), sulfamethoxazole (26/33), and tigecycline (25/33)
      showed the highest activity; clofazimine (20/33) and doxycycline (18/33) showed
      intermediate activity; and rifapentine (13/33), rifabutin (13/33), and
      minocycline (11/33) showed low antimicrobial activity, closely followed by
      thioacetazone (10/33) and pasiniazid (10/33), against the tested organisms.
      According to their susceptibility profiles, the slowly growing species
      Mycobacterium avium and Mycobacterium simiae were the least susceptible to the
      tested drugs, whereas Mycobacterium intracellulare, Mycobacterium asiaticum,
      Mycobacterium scrofulaceum, Mycobacterium szulgai, Mycobacterium branderi, and
      Mycobacterium holsaticum were the most susceptible. Conclusions. In summary,
      cephalosporins and macrolides, particularly cefmetazole, azithromycin,
      clarithromycin, and roxithromycin, showed good antimicrobial activity against the
      reference strains of SGM.

PMID- 28512636
TI  - Expression of YAP/TAZ in Keratocystic Odontogenic Tumors and Its Possible
      Association with Proliferative Behavior.
AB  - The aim of this study is to clarify whether YAP/TAZ is involved in the
      pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT).
      The expression levels of YAP/TAZ and downstream proteins and genes in normal oral
      mucosa (OM) and KCOT were determined and compared by immunohistochemistry and
      real-time quantitative PCR. The results showed that the expression of YAP/TAZ and
      downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with
      upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of
      transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes
      (CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are
      also upregulated in the KCOT. In addition, the results from Spearman rank
      correlation test revealed the close relationship between YAP/TAZ and Ki-67, which
      was further evidenced by double-labelling immunofluorescence that revealed a
      synchronous distribution for YAP/TAZ with Ki-67 in KCOT samples. All the data
      suggested YAP/TAZ might be involved in the proliferative behavior of KCOT.

PMID- 28512637
TI  - Positive Correlation between IP-10 and IFN-gamma Levels in Rhesus Monkeys (Macaca
      mulatta) with Either Naturally Acquired or Experimental Infection of
      Mycobacterium tuberculosis.
AB  - Numerous studies identify that IP-10 and IFN-gamma are involved in leucocyte
      migration and activation and regarded as promising surrogate biomarkers in human
      and bovine tuberculosis infection, but there is lack of evidence for IP-10 in
      nonhuman primates. In this study, we directly determined IP-10 and IFN-gamma
      levels in plasma from 30 healthy monkeys, 30 monkeys with naturally acquired
      tuberculosis, 4 monkeys experimentally infected with tuberculosis, and PPD
      stimulated whole blood of 14 monkeys with naturally acquired tuberculosis by
      ELISA. Higher plasma levels of IP-10 and IFN-gamma were observed in natural
      tuberculosis monkeys than in healthy controls. The dynamic changes of plasma IP
      10 and IFN-gamma in experimental infections showed consistent representation of a
      transient increase during the infection period. After PPD stimulation, release of
      IP-10 and IFN-gamma is significantly induced in natural tuberculosis monkeys, but
      the stimulation index of IP-10 was significantly lower than IFN-gamma. Further
      analysis showed that positive correlation between IP-10 and IFN-gamma existed in
      healthy and tuberculosis monkeys. Our findings support plasma IP-10 and IFN-gamma
      as biomarkers for monitoring ongoing inflammation of nonhuman primate
      tuberculosis, and IFN-gamma is a more valuable diagnostic biomarker.

PMID- 28512638
TI  - Seroprevalence and Risk Factors of Bluetongue Virus Infection in Tibetan Sheep
      and Yaks in Tibetan Plateau, China.
AB  - Bluetongue (BT), caused by bluetongue virus (BTV), is an arthropod-borne viral
      disease in ruminants. However, information about BTV infection in yaks in China
      is limited. Moreover, no such data concerning BTV in Tibetan sheep is available.
      Therefore, 3771 serum samples were collected from 2187 Tibetan sheep and 1584
      yaks between April 2013 and March 2014 from Tibetan Plateau, western China, and
      tested for BTV antibodies using a commercially available ELISA kit. The overall
      seroprevalence of BTV was 17.34% (654/3771), with 20.3% (443/2187) in Tibetan
      sheep and 13.3% (211/1584) in yaks. In the Tibetan sheep group, the
      seroprevalence of BTV in Luqu, Maqu, Tianzhu, and Nyingchi Prefecture was 20.3%,
      20.8%, 20.5%, and 19.1%, respectively. The seroprevalence of BTV in different
      season groups varied from 16.5% to 23.4%. In the yak group, BTV seroprevalence
      was 12.6%, 15.5%, and 11.0% in Tianzhu, Maqu, and Luqu counties, respectively.
      The seroprevalence in different seasons was 12.6%, 15.5%, 15.4%, and 9.0% in
      spring, summer, autumn, and winter, respectively. The season was the major risk
      factor concerning BTV infection in yaks (P < 0.05). The date of the BTV
      seroprevalence in Tibetan sheep and yaks provides baseline information for
      controlling BT in ruminants in western China.

PMID- 28512639
TI  - Inhibitory Effect of Chemical Constituents Isolated from Artemisia iwayomogi on
      Polyol Pathway and Simultaneous Quantification of Major Bioactive Compounds.
AB  - Blocking the polyol pathway plays an important role preventing diabetic
      complications. Therefore, aldose reductase (AR) and advanced glycation
      endproducts (AGEs) formation has significant effect on diabetic complications.
      Artemisia iwayomogi has long been used as treatment of various diseases in Korea.
      However, no literatures have reported on AR and AGEs formation inhibitory
      activities of A. iwayomogi. For these reasons, we aimed to assess that A.
      iwayomogi had potential as anti-diabetic complications agents. We led to
      isolation of two coumarins (1 and 2), nine flavonoids (3-11), five caffeoylquinic
      acids (12-16), three diterpene glycosides (17-19), and one phenolic compound (20)
      from A. iwayomogi. Among them, hispidulin (4), 6-methoxytricin (6),
      arteanoflavone (7), quercetin-3-gentiobioside (10), 1,3-di-O-caffeoylquinic acid
      (13), and suavioside A (18) were first reported on the isolation from A.
      iwayomogi. Not only two coumarins (1 and 2), nine flavonoids (3-11), and five
      caffeoylquinic acids (12-16) but also extracts showed significant inhibitor on AR
      and AGEs formation activities. We analyzed contents of major bioactive compounds
      in Korea's various regions of A. iwayomogi. Overall, we selected Yangyang,
      Gangwon-do, from June, which contained the highest amounts of bioactive
      compounds, as suitable areas for cultivating A. iwayomogi as preventive or
      therapeutic agent in the treatment of diabetic complications.

PMID- 28512640
TI  - Relationship between HLA-DQ Gene Polymorphism and Hepatitis B Virus Infection.
AB  - Hepatitis B virus (HBV) infection is the predominant risk factor for chronic
      hepatitis B (CHB). The association between HBV infection and human leukocyte
      antigen- (HLA-) DQ polymorphism (rs2856718 and rs7453920) has been demonstrated
      in other studies; however, the results were controversial or inconclusive.
      Therefore, to derive a more precise estimation of the association, a meta
      analysis was performed. Crude odds ratios (ORs) and their 95% confidence
      intervals (CIs) were used to assess the strength of association between HLA-DQ
      polymorphism (rs2856718 and rs7453920) and HBV infection risk. A total of 11
      articles were used to evaluate the effect of the two polymorphisms on risk of HBV
      infection. The pooled data showed that HLA-DQ rs2856718-G polymorphism showed
      protection against HBV infection, and rs2856718-A was a risk factor for chronic
      HBV infection. The pooled risk estimates indicated that HLA-DQ rs7453920-A
      polymorphism was associated with decreased risk of HBV infection, and rs7453920-G
      serves as a risk factor in HBV infection. However, these stratified analyses were
      lacking credibility due to the limitation of correlational study numbers; further
      investigation on a large population and different ethnicities is warranted.

PMID- 28512641
TI  - Podocyte Autophagy: A Potential Therapeutic Target to Prevent the Progression of
      Diabetic Nephropathy.
AB  - Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD),
      becomes a worldwide problem. Ultrastructural changes of the glomerular filtration
      barrier, especially the pathological changes of podocytes, lead to proteinuria in
      patients with diabetes. Podocytes are major components of glomerular filtration
      barrier, lining outside of the glomerular basement membrane (GBM) to maintain the
      permeability of the GBM. Autophagy is a high conserved cellular process in
      lysosomes including impaired protein, cell organelles, and other contents in the
      cytoplasm. Recent studies suggest that activation of autophagy in podocytes may
      be a potential therapy to prevent the progression of DN. Here, we review the
      mechanisms of autophagy in podocytes and discuss the current studies about
      alleviating proteinuria via activating podocyte autophagy.

PMID- 28512643
TI  - Diagnostic and Research Aspects of Small Intestinal Disaccharidases in Coeliac
      Disease.
AB  - Disaccharidases (DS) are brush border enzymes embedded in the microvillous
      membrane of small intestinal enterocytes. In untreated coeliac disease (CD), a
      general decrease of DS activities is seen. This manuscript reviews different
      aspects of DS activities in CD: their utility in the diagnosis and their
      application to in vitro toxicity testing. The latter has never been established
      in CD research. However, with the recent advances in small intestinal organoid
      techniques, DS might be employed as a biomarker for in vitro studies. This
      includes establishment of self-renewing epithelial cells raised from tissue,
      which express differentiation markers, including the brush border enzymes.
      Determining duodenal DS activities may provide additional information during the
      diagnostic workup of CD: (i) quantify the severity of the observed histological
      lesions, (ii) provide predictive values for the grade of mucosal villous atrophy,
      and (iii) aid diagnosing CD where minor histological changes are seen. DS can
      also provide additional information to assess the response to a gluten-free diet
      as marked increase of their activities occurs four weeks after commencing it.
      Various endogenous and exogenous factors affecting DS might also be relevant when
      considering investigating the role of DS in other conditions including noncoeliac
      gluten sensitivity and DS deficiencies.

PMID- 28512645
TI  - Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine
      Kinases in Human Neutrophils.
AB  - Neutrophils play a critical role in innate immunity and also influence adaptive
      immune responses. This occurs in good part through their production of
      inflammatory and immunomodulatory cytokines, in conjunction with their prolonged
      survival at inflamed foci. While a picture of the signaling machinery underlying
      these neutrophil responses is now emerging, much remains to be uncovered. In this
      study, we report that neutrophils constitutively express various Src family
      isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine
      kinases selectively hinders inflammatory cytokine generation by acting
      posttranscriptionally. Accordingly, STK or Syk inhibition decreases the
      phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved
      in translational control. By contrast, delayed apoptosis appears to be
      independent of either STKs or Syk. Our data therefore significantly extend our
      understanding of which neutrophil responses are governed by STKs and Syk and
      pinpoint some signaling intermediates that are likely involved. In view of the
      foremost role of neutrophils in several chronic inflammatory conditions, our
      findings identify potential molecular targets that could be exploited for future
      therapeutic intervention.

PMID- 28512642
TI  - Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy.
AB  - Diabetic nephropathy (DN) is manifested as increased urinary protein level,
      decreased glomerular filtration rate, and final renal dysfunction. DN is the
      leading cause of end-stage renal disease worldwide and causes a huge societal
      healthcare burden. Since satisfied treatments are still limited, exploring new
      strategies for the treatment of this disease is urgently needed. Oxidative stress
      takes part in the initiation and development of DN. In addition, nuclear factor
      erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to
      oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the
      treatment of DN. In current review, we discussed and summarized the therapeutic
      effects of Nrf2 activation on DN from both basic and clinical studies.

PMID- 28512644
TI  - Analysis of Serum Cytokines and Single-Nucleotide Polymorphisms of SOD1, SOD2,
      and CAT in Erysipelas Patients.
AB  - Increased free radical production had been documented in group A (beta-hemolytic)
      streptococcus infection cases. Comparing 71 erysipelas patients to 55 age-matched
      healthy individuals, we sought for CAT, SOD1, and SOD2 single polymorphism
      mutation (SNPs) interactions with erysipelas' predisposition and serum cytokine
      levels in the acute and recovery phases of erysipelas infection. Whereas female
      patients had a higher predisposition to erysipelas, male patients were prone to
      having a facial localization of the infection. The presence of SOD1 G7958, SOD2
      T2734, and CAT C262 alleles was linked to erysipelas' predisposition. T and C
      alleles of SOD2 T2734C individually were linked to patients with bullous and
      erythematous erysipelas, respectively. G and A alleles of SOD1 G7958A
      individually were associated with lower limbs and higher body part localizations
      of the infection, respectively. Serum levels of IL-1beta, CCL11, IL-2Ralpha,
      CXCL9, TRAIL, PDGF-BB, and CCL4 were associated with symptoms accompanying the
      infection, while IL-6, IL-9, IL-10, IL-13, IL-15, IL-17, G-CSF, and VEGF were
      associated with predisposition and recurrence of erysipelas. While variations of
      IL-1beta, IL-7, IL-8, IL-17, CCL5, and HGF were associated with the SOD2 T2734C
      SNP, variations of PDFG-BB and CCL2 were associated with the CAT C262T SNP.

PMID- 28512648
TI  - Revision of biliary sphincterotomy by re-cut, balloon dilation or temporary
      stenting: comparison of clinical outcome and complication rate (with video).
AB  - Background and study aims Revision of endoscopic retrograde
      cholangiopancreatography (ERCP) may be necessary following previous biliary
      endoscopic sphincterotomy for recurrent biliary symptoms related to biliary stone
      recurrence, cholangitis or post-biliary endoscopic sphincterotomy (bEST)
      papillary stenosis and cholestasis. The aim of this retrospective study was to
      evaluate the clinical outcome and complication rate associated with re-cut,
      balloon dilation and biliary metal stenting in revision ERCP. Patients and
      methods From January 2010 to January 2015, 139 subjects with stigma of a previous
      sphincterotomy required a revision ERCP (64 Men/75 Women; mean age 71 years;
      range 32 - 101 years). The most appropriate technique (re-cut, balloon dilation
      or fully covered self-expandable metal stent [FCSEMS] placement) was tailored
      according to underlying pathologies and anatomical features. Results Technical
      success was achieved in all cases (100 %). Clinical success (definitive clearance
      of common bile duct stones and liver test normalization) was achieved in 127 out
      of 139 patients (91.4 %) with a mean follow up of 12 months. 12 clinical failures
      occurred: 11 patients required a new ERCP after an average of 9 months meanwhile
      1 patient required surgery for definite treatment. The overall complication rate
      was 9 % (13 /139) with 5 acute complications (intra-procedural) and 8 short-term
      complications (before 1 month). Group specific overall complication rates were as
      follow: re-cut 11.5 % (8 bleeds and 3 perforations), balloon dilation 25 % (4
      mild PEP [post-ERCP pancreatitis]), FCSEMS 14.3 % (1 moderate PEP), re-cut +
      balloon dilation and re-cut + FCSEMS 0 %. A statistically significant higher risk
      of post-ERCP pancreatitis was highlighted in the balloon dilation group meanwhile
      re-cut was burdened by a higher risk of bleeding and perforation. Conclusions
      Revision ERCP following previous bEST is a feasible procedure enabling clinical
      success in most cases. Different approaches are available and must be considered
      according to underlying pathologies. Re-cut is burdened by a higher risk of
      perforation and bleeding compared to balloon dilation and SEMS meanwhile balloon
      dilation is associated to increased risk of PEP.

PMID- 28512647
TI  - Early esophagogastroduodenoscopy is associated with better Outcomes in upper
      gastrointestinal bleeding: a nationwide study.
AB  - Background and study aims We analyzed NIS (National Inpatient Sample) database
      from 2007 - 2013 to determine if early esophagogastroduodenoscopy (EGD) (24
      hours) for upper gastrointestinal bleeding improved the outcomes in terms of
      mortality, length of stay and costs. Patients and methods Patients were
      classified as having upper gastrointestinal hemorrhage by querying all diagnostic
      codes for the ICD-9-CM codes corresponding to upper gastrointestinal bleeding.
      For these patients, performance of EGD during admission was determined by
      querying all procedural codes for the ICD-9-CM codes corresponding to EGD; early
      EGD was defined as having EGD performed within 24 hours of admission and late EGD
      was defined as having EGD performed after 24 hours of admission. Results A total
      of 1,789,532 subjects with UGIH were identified. Subjects who had an early EGD
      were less likely to have hypovolemia, acute renal failure and acute respiratory
      failure. On multivariable analysis, we found that subjects without EGD were 3
      times more likely to die during the admission than those with early EGD. In
      addition, those with late EGD had 50 % higher odds of dying than those with an
      early EGD. Also, after adjusting for all factors in the model, hospital stay was
      on average 3 and 3.7 days longer for subjects with no or late EGD, respectively,
      then for subjects with early EGD. Conclusion Early EGD (within 24 hours) is
      associated with lower in-hospital mortality, morbidity, shorter length of stay
      and lower total hospital costs.

PMID- 28512646
TI  - MRI in Glioma Immunotherapy: Evidence, Pitfalls, and Perspectives.
AB  - Pseudophenomena, that is, imaging alterations due to therapy rather than tumor
      evolution, have an important impact on the management of glioma patients and the
      results of clinical trials. RANO (response assessment in neurooncology) criteria,
      including conventional MRI (cMRI), addressed the issues of pseudoprogression
      after radiotherapy and concomitant chemotherapy and pseudoresponse during
      antiangiogenic therapy of glioblastomas (GBM) and other gliomas. The development
      of cancer immunotherapy forced the identification of further relevant response
      criteria, summarized by the iRANO working group in 2015. In spite of this, the
      unequivocal definition of glioma progression by cMRI remains difficult
      particularly in the setting of immunotherapy approaches provided by checkpoint
      inhibitors and dendritic cells. Advanced MRI (aMRI) may in principle address this
      unmet clinical need. Here, we discuss the potential contribution of different
      aMRI techniques and their indications and pitfalls in relation to biological and
      imaging features of glioma and immune system interactions.

PMID- 28512650
TI  - Effect of antimicrobial photodynamic therapy ?and laser alone as adjunct to
      mechanical debridement in the management of halitosis: A systematic review.
AB  - OBJECTIVE: The aim of the present study was to assess the efficacy of laser
      therapy (LT) and antimicrobial photodynamic therapy (aPDT) as adjunct to
      mechanical debridement (MD) on the management of halitosis. DATA SOURCES: In
      order to address the focused question "Is MD with adjunct LT and/or aPDT more
      effective in the management of halitosis compared with MD alone?" an electronic
      search without time or language restrictions was conducted up to January 2017 in
      indexed databases using the combination of different key words including
      photochemotherapy, lasers, light, photodynamic therapy, halitosis, and bad
      breath. The exclusion criteria included qualitative and/or quantitative reviews,
      case reports, case series, commentaries, letters to the editor, interviews, and
      updates. RESULTS: Six randomized control trials were included and processed for
      data extraction. Results from all studies reported that MD with adjunct LT or
      aPDT is more effective in reducing halitosis and/or volatile sulfur compounds
      concentration associated with oral conditions compared with MD alone. One study
      reported a significant reduction in bacterial colony forming units on the dorsum
      of the tongue among patients with coated tongue receiving MD with aPDT compared
      with MD alone. CONCLUSION: The efficacy of aPDT and/or LT on halitosis management
      remains unclear. Further well-designed randomized clinical trials assessing the
      efficacy of mechanical debridement with LT or aPDT on the halitosis treatment are
      needed.

PMID- 28512651
TI  - Premium protocol for planning a periodontal-restorative approach: Conservative,
      predictable, ?and reproducible.
AB  - Planning oral rehabilitation that involves an interdisciplinary approach is
      challenging, especially when it includes changes in the morphologic aspects of
      teeth and the architecture of gingival tissues. Patients commonly complain about
      the esthetics of maxillary anterior teeth, especially when diastemata are
      present. A guideline known as the golden proportion can be used to establish
      adequate width distribution of anterior teeth. Tooth proportion is also affected
      by incisogingival tooth length, hence gingival contouring should be evaluated as
      well. In these situations, the width-to-height ratio of 0.75:0.78 in the
      maxillary anterior teeth could be used to obtain wax-ups and a surgical guide,
      resulting in a more predictable esthetic outcome. Therefore, this clinical report
      describes a protocol for the planning of a periodontal-restorative approach with
      two wax-ups and a surgical guide using the golden proportion width-to-height
      ratio of 0.75:0.78 for the treatment of maxillary anterior teeth with diastemata
      using minimum thickness lithium disilicate veneers.

PMID- 28512649
TI  - Purification and Characterization of Schwann Cells from Adult Human Skin and
      Nerve.
AB  - Despite its modest capacity for regeneration, peripheral nervous system injury
      often results in significant long-term disability. Supplementing peripheral
      nervous system injury with autologous Schwann cells (SCs) may serve to rejuvenate
      the postinjury environment to enhance regeneration and ultimately improve
      functional outcomes. However, human nerve-derived SC (hN-SC) collection
      procedures require invasive surgical resection. Here, we describe the
      characterization of SCs from adult human skin (hSk-SCs) of four male donors
      ranging between 27 and 46 years old. Within five weeks of isolating and culturing
      adherent mixed skin cells, we were able to obtain 3-5 million purified SCs. We
      found that hSk-SCs appeared transcriptionally indistinguishable from hN-SCs with
      both populations exhibiting expression of SC genes including: SOX10, SOX9, AP2A1,
      CDH19, EGR1, ETV5, PAX3, SOX2, CX32, DHH, NECL4, NFATC4, POU3F1, S100B, and YY1.
      Phenotypic analysis of hSk-SCs and hN-SCs cultures revealed highly enriched
      populations of SCs indicated by the high percentage of NES+ve, SOX10+ve, s100+ve
      and p75+ve cells, as well as the expression of a battery of other SC-associated
      proteins (PAX3, CDH19, ETV5, SOX2, POU3F1, S100B, EGR2, and YY1). We further show
      that both hSk-SCs and hN-SCs are capable of promoting axonal growth to similar
      degrees and that a subset of both associate with regenerating axons and form
      myelin following transplantation into the injured mouse sciatic nerve.
      Interestingly, although the majority of both hSk-SCs and hN-SCs maintained SOX10
      immunoreactivity following transplant, only a subset of each activated the
      promyelinating factor, POU3F1, and were able to myelinate. Taken together, we
      demonstrate that adult hSk-SCs are genetically and phenotypically
      indistinguishable to hN-SCs.

PMID- 28512652
TI  - Comparison of simplistic biofilm models for ?evaluating irrigating solutions.
AB  - OBJECTIVE: Many innovations have recently been implemented in the field of
      endodontics, often based on a variety of in-vitro/ex-vivo test setups. It was the
      goal of this research to compare different biofilm models for evaluating the
      effectiveness of rinsing solutions. METHOD AND MATERIALS: Three different models
      have been applied in this study, including petri dishes with nutrient medium,
      arrays of human dentin disks, and split bovine root segments. The susceptibility
      of biofilms formed by Enterococcus faecalis to commonly used endodontic irrigants
      was tested. RESULTS: While citric acid 3% did not show an inhibitory effect on
      solid medium, mean maximum inhibition areolae of 9.8 +/- 1.6 mm were found for
      sodium hypochlorite 3%. Fluorescein solution was shown to penetrate dentin
      tubules to a depth of 0.5 to 1 mm, indicating that the dentin tubules are not
      freely accessible, but clotted by E faecalis biofilms. Rinsing root canals with a
      combination of citric acid, hydrogen peroxide, chlorhexidine, and sodium
      hypochlorite removed bacterial biofilms from the dentin tubules only to a depth
      of 0.5 mm, while bacteria in deeper regions were not affected. CONCLUSION:
      Standard irrigating solutions inhibit bacterial growth; however, due to the
      morphology of the tooth, the effect of irrigating media is restricted to the root
      canal and the adjacent volume of dentin tubules. Results from standardizable
      diffusion tests seem not to be predictive for clinical performance of irrigating
      solutions.

PMID- 28512658
TI  - Effect of the material properties on the crumpling of a thin sheet.
AB  - While simple at first glance, the dense packing of sheets is a complex phenomenon
      that depends on material parameters and the packing protocol. We study the effect
      of plasticity on the crumpling of sheets of different materials by performing
      isotropic compaction experiments on sheets of different sizes and elasto-plastic
      properties. First, we quantify the material properties using a dimensionless
      foldability index. Then, the compaction force required to crumple a sheet into a
      ball as well as the average number of layers inside the ball are measured. For
      each material, both quantities exhibit a power-law dependence on the diameter of
      the crumpled ball. We experimentally establish the power-law exponents and find
      that both depend nonlinearly on the foldability index. However the exponents that
      characterize the mechanical response and morphology of the crumpled materials are
      related linearly. A simple scaling argument explains this in terms of the
      buckling of the sheets, and recovers the relation between the crumpling force and
      the morphology of the crumpled structure. Our results suggest a new approach to
      tailor the mechanical response of the crumpled objects by carefully selecting
      their material properties.

PMID- 28512653
TI  - Simplified technique for easy extraction of impacted supernumerary teeth using
      guided surgery.
AB  - Most mesiodens remain impacted and can affect the growth and development of
      adjacent permanent teeth. Impacted mesiodens are usually located in an
      intraosseous position associated with complicated anatomical structures,
      necessitating minimally invasive surgical approaches. This article demonstrates a
      simple customized surgical stent for extraction of impacted mesiodens. Its use
      and advantages are described.

PMID- 28512659
TI  - Extensive characterization of magnetic microrods observed using optical
      microscopy.
AB  - The usage of micro or nanorods is steadily increasing in various applications
      from fundamental research to industry. Therefore their geometrical, mechanical
      and eventually magnetic properties need to be well determined. Here, using an
      optical microscope equipped with magnetic tweezers, we report an experimental
      procedure to obtain all those information on a single magnetic rod. In
      particular, we measure magnetic susceptibility chi by analyzing the deformation
      of a rod subjected to a uniform magnetic field. To do so, we refine a theoretical
      model which takes into account the variation of chi with the internal field. We
      prove experimentally that this model yields consistent measurements, at any value
      of the field strength and the incidence angle. From the combination of the
      different measurements, we also deduce the number of iron oxide nanoparticles
      which are embedded within the polymer matrix of the superparamagnetic rods under
      study.

PMID- 28512660
TI  - Selective protein recognition in supported lipid bilayer arrays by tailored, dual
      mode deep cavitand hosts.
AB  - Self-folding deep cavitands with variably functionalized upper rims are able to
      selectively immobilize proteins at a biomimetic supported lipid bilayer surface.
      The immobilization process takes advantage of the dual-mode binding capabilities
      of the hosts, combining a defined binding pocket with upper rim charged/H-bonding
      groups. A variety of proteins can be selectively immobilized at the bilayer
      interface, either via complementary charge/H-bonding interactions, cavity-based
      molecular recognition, or a combination of both. The immobilization process can
      be used to bind unmodified native proteins, epitopes for bioadhesion, or proteins
      covalently modified with suitable RNMe3+ binding "handles" and charged groups
      that can either match or mismatch with the cavitand rim. The immobilization
      process can be monitored in real time using surface plasmon resonance (SPR)
      spectroscopy, and applied to the construction of cavitand:lipid arrays using the
      hosts and trehalose vitrified phospholipid vesicles. The selective, dual-mode
      protein recognition is maintained in the arrays, and can be visualized using SPR
      imaging.

PMID- 28512662
TI  - A hospital-wide transition from paper to digital problem-oriented clinical notes.
      A descriptive history and cross-sectional survey of use, usability, and
      satisfaction.
AB  - OBJECTIVES: To evaluate the use, usability, and physician satisfaction of a
      locally developed problem-oriented clinical notes application that replaced paper
      based records in a large Dutch university medical center. METHODS: Using a
      clinical notes database and an application event log file and a cross-sectional
      survey of usability, authors retrospectively analyzed system usage for medical
      specialties, users, and patients over 4 years. A standardized questionnaire
      measured usability. Authors analyzed the effects of sex, age, professional
      experience, training hours, and medical specialty on user satisfaction via
      univariate analysis of variance. Authors also examined the correlation between
      user satisfaction in relation to users' intensity of use of the application.
      RESULTS: In total 1,793 physicians used the application to record progress notes
      for 219,755 patients. The overall satisfaction score was 3.2 on a scale from 1
      (highly dissatisfied) to 5 (highly satisfied). A statistically significant
      difference occurred in satisfaction by medical specialty, but no statistically
      significant differences in satisfaction took place by sex, age, professional
      experience, or training hours. Intensity of system use did not correlate with
      physician satisfaction. CONCLUSIONS: By two years after the start of the
      implementation, all medical specialties utilized the clinical notes application.
      User satisfaction was neutral (3.2 on a 1-5 scale). Authors believe that the
      significant factors facilitating this transition mirrored success factors
      reported by other groups: a generic, consistent, and transparent design of the
      application; intensive collaboration; continuous monitoring; and an incremental
      rollout.

PMID- 28512663
TI  - Advancing the integration of hospital IT. Pitfalls and perspectives when
      replacing specialized software for high-risk environments with enterprise system
      extensions.
AB  - BACKGROUND: Planning and controlling surgical operations hugely impacts upon
      productivity, patient safety, and surgeons' careers. Established, specialized
      software for this task is being increasingly replaced by "Operating Room (OR)
      modules" appended to enterprise-wide resource planning (ERP) systems. As a
      result, usability problems are re-emerging and require developers' attention.
      OBJECTIVE: Systematic evaluation of the functionality and social repercussions of
      a global, market-leading IT business control system (SAP R3, Germany), adapted
      for real-time OR process steering. METHODS: Field study involving document
      analyses, interviews, and a 73-item survey addressed to 77 qualified (> 1-year
      system experience) senior planning executives (end users; "planners") working in
      surgical departments of university hospitals. RESULTS: Planners reported that 57%
      of electronic operation requests contained contradictory information. Key screens
      contained clinically irrelevant areas (36 +/- 29%). Compared to the legacy
      system, users reported either no improvements or worse performance, in regard to
      co-ordination of OR stakeholders, intra-day program changes, and safety. Planners
      concluded that the ERP-planning module was "non-intuitive" (66%), increased
      planning work (56%, p=0.002), and did not impact upon either organizational
      mishap spectrum or frequency. Interviews evidenced intra-institutional power
      shifts due to increased system complexity. Planners resented e.g. a trend towards
      increased personal culpability for mishap. CONCLUSIONS: Highly complex enterprise
      system extensions may not be directly suited to specific process steering tasks
      in a high risk/low error-environment like the OR. In view of surgeons' high
      primary task load, the repeated call for simpler IT is an imperative for ERP
      extensions. System design should consider a) that current OR IT suffers from an
      input limitation regarding planning-relevant real-time data, and b) that there
      are social processes that strongly affect planning and particularly ERP use
      beyond algorithms. Real improvement of clinical IT tools requires their
      independent evaluation according to standards developed for pharmaceutical
      subjects.

PMID- 28512664
TI  - Antidepressants have Anti-inflammatory Effects that may be Relevant to
      Dermatology: A Systematic Review.
AB  - There is increasing evidence of clinically relevant anti-inflammatory effects of
      monoaminergic antidepressants. PubMed and Ovid databases were searched
      systematically for the use and efficacy of antidepressants in association with 5
      common inflammatory skin disorders: chronic urticaria, psoriasis, atopic
      dermatitis, other eczema, and alopecia areata. From January 1984 to June 2016,
      publications included a total of 1,252 dermatological patients in 28 trials or
      case reports. These unambiguously reported a reduced burden of dermatological
      symptoms in relation to treatment with antidepressants. Several randomized
      controlled trials of first-generation antidepressants have been published, while
      studies of modern antidepressants are usually open-label, yet more informative,
      regarding patients' characteristics and study procedures. These overall positive
      findings may indicate a rationale, beyond treating comorbid psychiatric
      disorders, for the use of antidepressants in dermatology. Further research into
      modern tolerable antidepressants, including selective serotonin re-uptake
      inhibitors, mirtazapine and bupropion, is required.

PMID- 28512665
TI  - Involvement of u-opioid Receptors and kappa-opioid Receptors in Itch-related
      Scratching Behaviour of Imiquimod-induced Psoriasis-like Dermatitis in Mice.
AB  - The pathogenesis of psoriatic itch is poorly understood. The aim of this study
      was to investigate the involvement of opioid receptors in scratching behaviour of
      imiquimod-induced psoriasis-like dermatitis model mice. Topical application of 5%
      imiquimod cream to the rostral back skin of mice induced antihistamine-resistant
      scratching behaviour. The expression of u-opioid receptor (MOR) protein increased
      in the epidermis, dorsal root ganglia (DRG) and spinal cord of imiquimod-treated
      mice. In contrast, the expression of kappa-opioid receptor (KOR) protein
      decreased in the DRG and spinal cord of imiquimod-treated mice, and was
      undetectable in the epidermis of both groups. Topical or intraperitoneal
      administration of the MOR antagonist naloxone and oral administration of the
      centrally acting KOR agonist ICI-199,441 inhibited scratching behaviour, whereas
      oral administration of the peri-pherally-selective KOR agonist asimadoline did
      not. These results suggest that peripheral and central MOR and central KOR may be
      involved in the modulation of scratching behaviour in imiquimod-treated mice.

PMID- 28512666
TI  - Diagnostic Efficacy of Digital Dermoscopy and Clinical Findings in Thin Melanoma
      of the Lower Limbs.
AB  - The introduction of dermoscopy has improved the accuracy of diagnosis of
      melanoma. However, early stage melanoma can be difficult to diagnose. Eighty-nine
      cases of thin melanoma with a Breslow thickness <=1 mm located on the lower limb
      and diagnosed between 2008 and 2016 were assessed using 4 dermoscopic algorithms:
      (i) modified pattern analysis; (ii) ABCD rule of dermoscopy; (iii) 7-point
      checklist; and (iv) Menzies' method. Two groups of early stage melanomas of the
      legs were identified: "difficult to diagnose melanomas" (DDM) and "non-difficult
      to diagnose melanomas" (NDDM). In our series the dermoscopic features of DDM were
      difficult to differentiate from melanocytic naevi, and the reticular pattern was
      the most frequently observed. "Depigmentation" was the only specific criterion
      associated with DDM. The sensitivity of diagnostic systems for thin melanomas of
      the lower limbs was lower than in previous studies. This result could be related
      to the lower mean Breslow thickness of the invasive melanomas in our sample and
      the high number of melanomas in situ. In conclusion, early stage melanoma of the
      legs may be difficult to detect at clinical examination or with dermoscopic
      examination alone. Focusing on depigmentation in dermoscopy associated with
      anamnestic features could be a useful tool to detect difficult thin melanomas. In
      addition, sequential dermoscopy is recommended for high-risk patients with
      previous melanomas or atypical mole syndrome.

PMID- 28512667
TI  - Involvement of Leukotriene B4 Released from Keratinocytes in Itch-associated
      Response to Intradermal Interleukin-31 in Mice.
AB  - A recent study suggests that interleukin-31 (IL-31) exerts its effect via
      indirect mechanisms rather than through direct stimulation of cutaneous nerves.
      However, the underlying peripheral mechanisms of IL-31-induced itch in the skin
      remain unclear. Therefore, the present study investigated the peripheral
      mechanisms underlying IL-31-induced itch in mice. IL-31-induced itch-related
      response was inhibited by anti-allergic drugs (tranilast and azelastine), but not
      by an H1 histamine receptor antagonist (terfenadine). Furthermore, a 5
      lipoxygenase inhibitor (zileuton), but not a cyclooxygenase inhibitor
      (indomethacin), and a leuko-triene B4 (LTB4) receptor antagonist (CMHVA)
      attenuated the action of IL-31. IL-31 receptor-immunoreactivity was observed in
      the epidermis and primary sensory neurones. IL-31 receptor mRNA was expressed in
      mouse keratinocytes and dorsal root ganglia neurones. IL-31 increased the
      production of LTB4 in mouse keratinocytes. These results suggest that IL-31
      elicits itch not only through direct action on primary sensory neurones, but also
      by inducing LTB4 production in keratinocytes.

PMID- 28512668
TI  - Prevalence of Cancer in Adult Patients with Atopic Dermatitis: A Nationwide
      Study.
AB  - is missing (Short communication).

PMID- 28512669
TI  - Combined Fractional Treatment of Acne Scars Involving Non-ablative 1,550-nm
      Erbium-glass Laser and Micro-needling Radiofrequency: A 16-week Prospective,
      Randomized Split-face Study.
AB  - An optimized therapeutic regimen involving a non-ablative fractionated laser or
      radiofrequency therapy for acne scars has not yet been established. To evaluate
      whether the combination of a non-ablative fractional laser (NAF) and fractional
      micro-needling radiofrequency (FMR) has clinical advantages for the treatment of
      atrophic acne scars compared with NAF alone, a 16-week prospective, randomized
      split-face study was performed. Each facial side of a patient was treated with 3
      sessions of either NAF with FMR or NAF alone, with a 4-week interval between each
      session. Although both sides demonstrated significant decreases in the echelle
      d'evaluation clinique des cicatrices d'acne (ECCA) score, the facial side treated
      using the combination regimen demonstrated greater improvement in ECCA score
      regarding degree and onset time than the NAF-treated side. Histopathological and
      immunohistochemical results confirmed the clinical findings. This study
      demonstrated that a combination regimen involving NAF and FMR could be a viable
      option with satisfactory efficacy.

PMID- 28512670
TI  - Disrupted Skin Barrier is Associated with Burning Sensation after Topical
      Tacrolimus Application in Atopic Dermatitis.

PMID- 28512671
TI  - Biologic Therapies in HIV-infected Patients with Psoriasis: An Italian
      Experience.

PMID- 28512672
TI  - Sezary Syndrome with Nodal CD30-positive Manifestation Treated with Brentuximab
      Vedotin and Extracorporeal Photopheresis.

PMID- 28512674
TI  - Preparing pathology for precision medicine: challenges and opportunities.

PMID- 28512673
TI  - Hepatozoon caimani Carini, 1909 (Adeleina: Hepatozoidae) in wild population of
      Caiman yacare Daudin, 1801 (Crocodylia: Alligatoridae), Pantanal, Brazil.
AB  - Previous studies showed infections of Hepatozoon caimani in wild populations of
      caimans in wide regions from Brazil; some of those demonstrated that trophic
      chain are linked to natural infections through paratenic hosts or by the direct
      ingestion of vectors. These studies life cycle of H. caimani contributed
      inestimably to the knowledge of transmission routes, yet but lack enhancement
      tools for better detail of parasite. This study reports the forms in the blood
      and tissues, and also partial molecular characterization of the H. caimani
      following part of the 18S rRNA region. In the southern Pantanal, there were
      sampling 39 adult caimans (Caiman yacare), where 31 (79.5%) were parasitized by
      H. caimani. Free gametocytes had an average intensity of 19.6% and
      intraerythrocytic forms 7.42%, in the blood smears. In stained smears of the
      liver and lungs of naturally infected caimans which were examined, monozoic and
      dizoic cysts were found in these tissues, generally next to the vessels. In the
      histopathology, meronts were observed in the wall of vessels from liver and
      kidney ducts. Blood samples were forwarded to PCR process and produced amplicons
      with about 600 and 900 bp, respectively, for the primers HEPF300/HEP900 and
      HEMO1/HEMO2. This was the first report of molecular confirmation of Hepatozoon in
      populations of naturally infected caimans of morphological detail of the
      gametocytes in scanning electron microscopy and histology of merogony in livers
      and kidneys of C. yacare.

PMID- 28512675
TI  - Selection and characterization of an anaerobic microbial consortium with high
      adaptation to crude glycerol for 1,3-propanediol production.
AB  - Crude glycerol is an ideal feedstock for bioproduction of 1,3-propanediol (1,3
      PDO) while pure culture always shows low substrate tolerance and limited
      productivity. In this study, an anaerobic microbial consortium for conversion of
      crude glycerol was selected and its 1,3-PDO production capacity was evaluated.
      The consortium was obtained from anaerobic activated sludge by 19 serial
      transfers and mainly consisted of 94.64% Clostridiaceae and 4.47%
      Peptostreptococcaceae. The consortium adapted well with high glycerol
      concentration of 120 g/L as well as wide substrate concentration fluctuation from
      15 to 80 g/L, producing 60.61 and 82.66 g/L 1,3-PDO in the batch and fed-batch
      fermentation, with the productivity of 3.79 and 3.06 g/(L?h), respectively, which
      are among the best results published so far. Furthermore, mini consortia isolated
      by serial dilution exhibited similar microbial composition but gradually
      decreasing tolerance to crude glycerol. Four randomly selected Clostridium
      butyricum displayed different substrate tolerance and insufficient 1,3-PDO
      production capacity. This work demonstrated that the high adaptation to crude
      glycerol of the consortium was the collaborative effort of different individuals.

PMID- 28512678
TI  - Benefits of Long-Term Digital Support Following Bariatric Surgery Incorporating
      Views from a Patient Advisory Group.

PMID- 28512676
TI  - Different fermentation processes produced variants of an anti-CD52 monoclonal
      antibody that have divergent in vitro and in vivo characteristics.
AB  - The anti-CD52 antibody has already been approved for the treatment of patients
      with resistant chronic lymphocytic leukemia, relapsing-remitting multiple
      sclerosis, and has demonstrable efficacy against stem cell transplantation
      rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody
      (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified.
      The critical quality attributes of these mAb variants were characterized and the
      pharmacokinetics (PK) properties were investigated. Results showed that the
      perfusion culture achieved higher productivity, whereas the fed-batch culture
      produced more aggregates and acid components. Additionally, the perfusion culture
      produced similar fucose, more galactose and a higher proportion of sialic acid on
      the anti-CD52 mAb compared to the fed-batch culture. Furthermore, the perfusion
      process produced anti-CD52 mAb had higher complement-dependent cytotoxicity (CDC)
      efficacy than that produced by the fed-batch culture, a result probably linked to
      its higher galactose content. However, antibody produced by fed-batch and
      perfusion cultures showed similar PK profiles in vivo. In conclusion, perfusion
      is a more efficient method than fed-batch process in the production of functional
      anti-CD52 monoclonal antibody. Product quality variants of anti-CD52 mAb were
      found in different cell culture processes, which demonstrated different
      physiochemical and biological activities, but comparable PK properties. Whether
      these observations apply to all mAbs await further investigation.

PMID- 28512679
TI  - Multiphysics Modeling of the Atrial Systole under Standard Ablation Strategies.
AB  - The aim of this study was to develop a computational framework to compare the
      impact of standard ablation concepts on the mechanical performance of the atria,
      since different line combinations cannot be applied in practice to the same
      patient. For this purpuse, we coupled electro-mechano-hemodynamic mathematical
      models based on biophysical principles and simulate the contractile performance
      of the atria. We computed systolic pressures and volumes in two patient-specific
      atrial geometries (one of normal size and one hypertrophied) with various
      ablation concepts. We found that our computational model is able to detect the
      differences in the left atrial contractility and ejection fraction for various
      electrical activation sequences resulting from different ablation line
      combinations. We show that multiphysics modeling has the potential to quantify
      the hemodynamic performance of left atria for different ablation lines, which
      could be used as additional pre-operative clinical information for the choice of
      the ablation concept in the future.

PMID- 28512680
TI  - A Novel Idea to Improve Cardiac Output of Mechanical Circulatory Support Devices
      by Optimizing Kinetic Energy Transfer Available in Forward Moving Aortic Blood
      Flow.
AB  - Mechanical circulatory support devices (MCSDs) have gained widespread clinical
      acceptance as an effective heart failure (HF) therapy. The concept of harnessing
      the kinetic energy (KE) available in the forward aortic flow (AOF) is proposed as
      a novel control strategy to further increase the cardiac output (CO) provided by
      MCSDs. A complete mathematical development of the proposed theory and its
      application to an example MCSDs (two-segment extra-aortic cuff) are presented. To
      achieve improved device performance and physiologic benefit, the example MCSD
      timing is regulated to maximize the forward AOF KE and minimize retrograde flow.
      The proof-of-concept was tested to provide support with and without KE control in
      a computational HF model over a wide range of HF test conditions. The simulation
      predicted increased stroke volume (SV) by 20% (9 mL), CO by 23% (0.50 L/min),
      left ventricle ejection fraction (LVEF) by 23%, and diastolic coronary artery
      flow (CAF) by 55% (3 mL) in severe HF at a heart rate (HR) of 60 beats per minute
      (BPM) during counterpulsation (CP) support with KE control. The proposed KE
      control concept may improve performance of other MCSDs to further enhance their
      potential clinical benefits, which warrants further investigation. The next step
      is to investigate various assist technologies and determine where this concept is
      best applied. Then bench-test the combination of kinetic energy optimization and
      its associated technology choice and finally test the combination in animals.

PMID- 28512681
TI  - Evaluation of Immune Indices and Serum Vitamin D Content in Children with Atopic
      Dermatitis.
AB  - The influence of vitamin D on allergic diseases, including atopic dermatitis, is
      linked to the presence of vitamin D nuclear receptors in immune cells. The
      present study seeks to determine the possible relationship between serum vitamin
      D content and immune indices in children with atopic dermatitis. The study was
      conducted in 19 children with atopic dermatitis. The control consisted of 17 age
      matched healthy children. A single significant finding was a distinctly lower
      number of serum regulatory T cells in atopic dermatitis compared with controls (p
      < 0.00001). There were no appreciable differences between the two groups
      concerning the immunological indices such as the phenotypes: CD3, CD4, CD8,
      CD4/CD8, CD19, CD16/56, natural killer T cells, and anti-CD3 human leukocyte
      antigen - antigen D related cell surface receptor (HLA-DR3), or the percentage of
      lymphocytes, eosinophils, and the IgE level. We also revealed an inverse
      association between the serum vitamin D and the percentage of CD8+ cells (p <
      0.05; r = 0.62) in atopic dermatitis. In conclusion, the results point to a
      regulatory role of T cells in the pathogenesis of atopic dermatitis, but fail to
      substantiate the influence of vitamin D on the course of the disease.

PMID- 28512682
TI  - Causa formalis-detail matters.

PMID- 28512677
TI  - Heterogeneity of proliferative markers in pancreatic beta-cells of patients with
      severe hypoglycemia following Roux-en-Y gastric bypass.
AB  - AIMS: Severe postprandial hypoglycemia with neuroglycopenia is an increasingly
      recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery.
      Increased secretion of insulin and incretin hormones is implicated in its
      pathogenesis. Histopathologic examination of pancreas has demonstrated increased
      islet size and/or nuclear diameter in post-RYGB patients who underwent
      pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB +
      NG). We aimed to determine whether beta-cell proliferation or apoptosis is
      altered in RYGB + NG. METHODS: We performed an observational study to analyze
      markers of proliferation, apoptosis, cell cycle, and transcription factor
      expression in pancreatic tissue from affected RYGB + NG patients (n = 12),
      normoglycemic patients undergoing pancreatic surgery for benign lesions
      (controls, n = 6), and individuals with hypoglycemia due to insulinoma (n = 52).
      RESULTS: Proliferative cell nuclear antigen (PCNA) expression was increased in
      insulin-positive cells in RYGB + NG patients (4.5-fold increase, p < 0.001 vs.
      controls) and correlated with beta-cell mass. Ki-67 immunoreactivity was low in
      both RYGB + NG and controls, but did not differ between groups. Phospho-histone
      H3 levels did not differ between RYGB + NG and controls. PCNA and Ki-67 were both
      significantly lower in both controls and RYGB + NG than insulinomas. Markers of
      apoptosis and cell cycle (M30, p27, and p21) did not differ between groups. PDX1
      and menin exhibited similar expression patterns, while FOXO1 appeared to be more
      cytosolic in RYGB + NG. CONCLUSIONS: Markers of proliferation are heterogeneous
      in patients with severe post-RYGB hypoglycemia. Increased beta-cell proliferation
      in some individuals may contribute to increased beta-cell mass observed in
      severely affected patients.

PMID- 28512684
TI  - Therapeutic Applications of Classic Hallucinogens.
AB  - This chapter reviews what is known about the therapeutic uses of the serotonergic
      or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin
      that exert their effects primarily through agonist activity at serotonin 2A
      (5HT2A) receptors. Following a review of the history of human use and scientific
      study of these drugs, the data from clinical research are summarized, including
      extensive work on the use of classic hallucinogens in the treatment of alcoholism
      and other addictions, studies of the use of LSD and psilocybin to relieve
      distress concerning death, particularly in patients with advanced or terminal
      cancer, and more limited data concerning the use of classic hallucinogens to
      treat mood and anxiety disorders. A survey of possible mechanisms of clinically
      relevant effects is provided. The well-established safety of classic
      hallucinogens is reviewed. To provide a clinical perspective, case summaries are
      provided of two individuals who received treatment in recent controlled trials of
      psilocybin: one being treated for alcoholism, the other suffering from anxiety
      and depression related to fear of death due to a cancer diagnosis. Although
      promising early phase research conducted from the 1950s through the early 1970s
      was discontinued before firm conclusions could be reached concerning the efficacy
      of any of the classic hallucinogens for any clinical condition, the research that
      was conducted in that era strongly suggests that classic hallucinogens have
      clinically relevant effects, particularly in the case of LSD treatment of
      alcoholism. In the past decade, clinical trials have resumed investigating the
      effects of classic hallucinogens in the treatment of existential distress in the
      face of cancer, and in the treatment of addictions including alcoholism and
      nicotine addiction. The studies that have been completed to date are not
      sufficient to establish efficacy, but the outcomes have been very encouraging,
      and larger trials, up to and including phase 3, are now underway or being
      planned. Although research has elucidated many of the acute neurobiological and
      psychological effects of classic hallucinogens on humans, animals, and in vitro
      systems, the mechanisms of clinically relevant persisting effects remain poorly
      understood.

PMID- 28512683
TI  - Messenger RNA transport in the opportunistic fungal pathogen Candida albicans.
AB  - Candida albicans, a common commensal fungus, can cause disease in
      immunocompromised hosts ranging from mild mucosal infections to severe
      bloodstream infections with high mortality rates. The ability of C. albicans
      cells to switch between a budding yeast form and an elongated hyphal form is
      linked to pathogenicity in animal models. Hyphal-specific proteins such as cell
      surface adhesins and secreted hydrolases facilitate tissue invasion and host cell
      damage, but the specific mechanisms leading to asymmetric protein localization in
      hyphae remain poorly understood. In many eukaryotes, directional cytoplasmic
      transport of messenger RNAs that encode asymmetrically localized proteins allows
      efficient local translation at the site of protein function. Over the past two
      decades, detailed mechanisms for polarized mRNA transport have been elucidated in
      the budding yeast Saccharomyces cerevisiae and the filamentous fungus Ustilago
      maydis. This review highlights recent studies of RNA-binding proteins in C.
      albicans that have revealed intriguing similarities to and differences from known
      fungal mRNA transport systems. I also discuss outstanding questions that will
      need to be answered to reach an in-depth understanding of C. albicans mRNA
      transport mechanisms and the roles of asymmetric mRNA localization in polarized
      growth, hyphal function, and virulence of this opportunistic pathogen.

PMID- 28512686
TI  - Amygdala structure and core dimensions of the affective personality.
AB  - While biological models of human personality propose that socio-affective traits
      and skills are rooted in the structure of the amygdala, empirical evidence
      remains sparse and inconsistent. Here, we used a comprehensive assessment of the
      affective personality and tested its association with global, local, and
      laterality measures of the amygdala structure. Results revealed three broad
      dimensions of the affective personality that were differentially related to
      bilateral amygdala structures. Dysfunctional and maladaptive affective traits
      were associated with a global size and local volume reduction of the amygdala,
      whereas adaptive emotional skills were linked to an increased size of the left
      amygdala. Furthermore, reduced asymmetry in the bilateral global amygdala volume
      was linked to higher affective instability and might be a potential precursor of
      psychiatric disorders. This study demonstrates that structural amygdala measures
      provide a neural basis for all major dimensions of the human personality related
      to adaptive and maladaptive socio-affective functioning.

PMID- 28512685
TI  - Modeling brain lentiviral infections during antiretroviral therapy in AIDS.
AB  - Understanding HIV-1 replication and latency in different reservoirs is an ongoing
      challenge in the care of patients with HIV/AIDS. A mathematical model was created
      to describe and predict the viral dynamics of HIV-1 and SIV infection within the
      brain during effective combination antiretroviral therapy (cART). The
      mathematical model was formulated based on the biology of lentiviral infection of
      brain macrophages and used to describe the dynamics of transmission and
      progression of lentiviral infection in brain. Based on previous reports
      quantifying total viral DNA levels in brain from HIV-1 and SIV infections,
      estimates of integrated proviral DNA burden were made, which were used to
      calibrate the mathematical model predicting viral accrual in brain macrophages
      from primary infection. The annual rate at which susceptible brain macrophages
      become HIV-1 infected was estimated to be 2.90*10-7-4.87*10-6 per year for cART
      treated HIV/AIDS patients without comorbid neurological disorders. The
      transmission rate for SIV infection among untreated macaques was estimated to be
      5.30*10-6-1.37*10-5 per year. An improvement in cART effectiveness (1.6-48%)
      would suppress HIV-1 infection in patients without neurological disorders. Among
      patients with advanced disease, a substantial improvement in cART effectiveness
      (70%) would eradicate HIV-1 provirus from the brain within 3-32 (interquartile
      range 3-9) years in patients without neurological disorders, whereas 4-51
      (interquartile range 4-16) years of efficacious cART would be required for
      HIV/AIDS patients with comorbid neurological disorders. HIV-1 and SIV provirus
      burdens in the brain increase over time. A moderately efficacious antiretroviral
      therapy regimen could eradicate HIV-1 infection in the brain that was dependent
      on brain macrophage lifespan and the presence of neurological comorbidity.

PMID- 28512688
TI  - Perceptions of Exercise During Medical School.

PMID- 28512687
TI  - Added Value of Covered Stents in Transjugular Intrahepatic Portosystemic Shunt: A
      Large Single-Center Experience.
AB  - PURPOSE: Transjugular intrahepatic portosystemic shunts (TIPS) were historically
      placed using uncovered bare-metal stents. Current practice has now shifted toward
      the use of polytetrafluoroethylene (PTFE)-covered stents, given the improved
      primary patency seen with these stents. The aim of this study was to determine
      whether there is any added value, such as overall survival or stent patency, when
      using covered stents versus uncovered stents in TIPS placement in a large cohort.
      MATERIALS AND METHODS: From April 1995 to June 2012, a total of 744 consecutive
      adult patients underwent de novo TIPS placement (378 receiving uncovered stents,
      366 receiving covered stents). Information was obtained on demographics, baseline
      clinical variables, and outcomes after TIPS placement. Data were collected,
      compared, and analyzed to assess outcomes including mortality, primary patency
      (determined via repeat intervention), and secondary patency (determined via
      ultrasound parameters). RESULTS: Covered stents were associated with
      significantly improved primary patency (P < 0.001) and secondary patency (P <
      0.001) when compared with uncovered stents in TIPS procedures. Additionally,
      covered stents were associated with higher estimated overall survival rates and
      higher survival rates when TIPS was performed emergently and in patients with
      higher Model for End-Stage Liver Disease (MELD) scores. For example, in patients
      with MELD scores between 11 and 18, there was a predicted survival of 59.2% with
      covered stents versus 42.8% with uncovered stents at 1 year. CONCLUSION: This
      study demonstrated that covered stents offer the additional value of higher
      estimated overall survival and higher estimated survival in patients undergoing
      TIPS emergently and in those with higher MELD scores when compared to uncovered
      stents.

PMID- 28512689
TI  - Long-term results of fibular-Achilles tenodesis (Westin's tenodesis) for
      paralytic pes calcaneus: is hypercorrection avoidable? A longitudinal
      retrospective study.
AB  - PURPOSE: The purpose of this study was to review all cases of patients submitted
      to Westin's tenodesis, who had calcaneus feet secondary to myelomeningocele
      sequel, in order to evaluate the anatomical change provided by surgery and also
      to verify, in a long-term follow-up, the inversion of the deformity depending on
      the patient's age. METHODS: In this longitudinal retrospective study, all medical
      records of patients with myelomeningocele sequelae submitted to Westin's
      tenodesis from 1993 to 2013 in a public university hospital were reviewed.
      Patients were contacted for new clinical and radiographic evaluations after a
      minimum of 36 months after surgery. The calcaneotibial angle was measured and the
      shortening of the fibula was calculated as the "intermalleolar height". RESULTS:
      The study was based on 16 children (26 feet), aged 84.27 months on average at the
      time of tenodesis. The calcaneotibial angle increased significantly post
      operatively, from 63.77 degrees on average to 70.54 degrees. Intermalleolar
      height and valgus ankle did not change significantly. Most patients had
      plantigrade feet after surgery, without pressure ulcers, and were able to use
      orthoses. CONCLUSION: Westin's tenodesis, with or without other associated
      procedures, can correct or improve the calcaneus and valgus ankle deformity in
      patients with myelomeningocele sequelae. There was no association of the surgical
      result with age at the time of surgery. There was no inversion of the deformity
      in equinus during the follow-up time.

PMID- 28512690
TI  - Translational studies on a ready-to-use intramuscular injection of penethamate
      for bovine mastitis.
AB  - Bovine mastitis caused by bacterial infections of the mammary gland (udder) of
      dairy cows is a costly pathology for the dairy industry due to direct and
      indirect losses in production. Penethamate, a pro-drug of benzylpenicillin, is
      used by intramuscular injection (IM). The existing products are powders which
      must be reconstituted in water-for-injection and this presents difficulties in
      the field. Penethamate is too unstable to be formulated as an aqueous formulation
      but a chemically stable suspension formulation was possible in certain oils;
      however, some literature suggests that such formulations would have unacceptable
      prolonged release. The translational research proceeded iteratively from lab to
      the target species, rather than via laboratory animal trials. Pilot studies in
      cows suggested that some oily suspensions would give concentrations of
      benzylpenicillin, (in both blood and milk) comparable with those of the
      reconstituted product. A physicochemical screen and a low level in vitro-in vivo
      correlation (IVIVC) was cautiously used to guide selection of formulations for
      subsequent animal trials which have resulted in a lead formulation for good
      laboratory practices (GLP), good clinical practices (GCP) studies.

PMID- 28512691
TI  - Complete Circumferential Osseous Extension in the Acetabular Rim Occurs
      Regardless of Acetabular Coverage.
AB  - BACKGROUND: Complete circumferential osseous extension in the acetabular rim has
      been reported to occur in the deep hip with pincer impingement. However, this
      phenomenon occasionally is observed in dysplastic hips without pincer
      impingement, and the degree to which this finding might or might not be
      associated with hip pain, and how often it occurs bilaterally among patients, are
      not well characterized. QUESTIONS/PURPOSES: (1) To determine the proportion of
      patients with complete circumferential osseous extension in the acetabular rim
      using three-dimensional (3-D) CT in patients with and without hip pain who had CT
      scans obtained for various reasons. (2) To elucidate how often this complete
      circumferential osseous extension occurred bilaterally among those patients. (3)
      To investigate the relationship between the proportions of patients with complete
      circumferential osseous extension observed on CT scans among three different
      acetabular coverage groups: dysplasia, normal, and overcoverage. (4) To determine
      how often the finding of hip pain was associated with complete circumferential
      osseous extension. PATIENTS AND METHODS: Between September 2011 to July 2016, we
      evaluated 3788 patients with pelvic complaints such as hip, groin, thigh,
      buttock, or sacroiliac joint pain. We obtained consent from 26% (992 of 3788) of
      them, and obtained 3-D CT scans as part of that evaluation. For the current
      retrospective study, we excluded patients younger than 20 years or 80 years or
      older (181 patients), patients who had previous hip surgery (185 patients),
      patients with severe osteoarthritis with Tonnis Grades 2 or 3 (301 patients), and
      patients who could not have an accurate lateral center-edge (LCE) angle measured
      owing to poor-quality radiographs (24 patients), leaving 301 patients (602 hips)
      for this analysis. In this study population, patients reported pain in 131 hips
      (22%), defined as all types of hip pain except for trauma, including activity
      pain, pain with sports, pain on motion, and impingement pain; the others did not
      report hip pain. The mean age of the patients was 56 +/- 16 years, and the mean
      LCE angle was 26 degrees  +/- 8 degrees  (range, -9 degrees  to 47 degrees ). We
      first determined the proportion of patients with complete circumferential osseous
      extension in the acetabular rim using 3-D CT for those with and without hip pain
      who had CT obtained for various reasons. We next elucidated how often this
      complete circumferential osseous extension occurred bilaterally among the
      patients, and finally we investigated the relationship between the proportion of
      patients with complete circumferential osseous extension observed on CT scans
      among the three groups: dysplasia (defined as LCE angles of 22 degrees  or
      smaller), normal, and overcoverage (defined as LCE angles of 34 degrees  or
      larger) groups. We finally determined how often the finding was associated with
      hip pain attributable to complete circumferential osseous extension. RESULTS: The
      proportion of patients with complete circumferential osseous extension was 6% (18
      of 301 patients). Eighty-nine percent (16 of 18) of the patients had bilateral
      complete circumferential osseous extension. There were no differences in the
      proportions of patients with complete circumferential osseous extension among the
      three groups: 5.3% (odds ratio [OR], 1.02; 95% CI, 0.45-2.31; p = 0.97), 5.3%,
      and 7.4% (OR, 0.70; 95% CI, 0.28-1.73; p = 0.44) in the dysplasia, normal, and
      overcoverage groups, respectively, with the numbers available. Eighteen percent
      (six of 34) of the hips with complete circumferential osseous extension had pain.
      CONCLUSIONS: Complete circumferential osseous extension in the acetabular rim is
      relatively uncommon. When it occurs, it usually is bilateral, it occurs
      regardless of acetabular coverage, and it is associated with pain in a minority
      of patients. LEVEL OF EVIDENCE: Level III, prognostic study.

PMID- 28512694
TI  - Erratum to: Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A
      Systematic Review and Meta-Analysis.

PMID- 28512696
TI  - Synthesis, Characterization, Electrochemical and Surface Morphologies of
      Polyazomethines Containing Silane and Phosphazene Units.
AB  - Polyazomethines containing silane and phosphazene groups were synthesized via
      elimination reactions of dihydroxy compounds containing imine bonding with
      phosphazane and silane dichloride. The structures of monomers and polymers
      containing phosphazane and silane groups were supported by 1H-NMR, 13C-NMR, FT-IR
      and UV-Vis techniques. Electrochemical properties of the prepared Schiff bases
      and polymers were given by cyclic voltammetric (CV) analysis. Thermal properties
      of synthesized monomers and polymers were determined by TG-DTA and TG-DTA, DMA
      and DSC techniques, respectively. Molecular mass distributions of polymers are
      determined with gel permeation chromatography (GPC) measurement. Morphologic
      images of polymers containing heteroatom (silane/phosphazene) and azomethine
      linkage in the main chain were investigated by SEM techniques. The
      electrochemical band gap values of SB-1, SB-2, P-1, P-2 and P-3 compounds were
      found as 3.09, 3.30, 2.63, 3.07 and 3.04 eV, respectively.

PMID- 28512692
TI  - Virtual Reality-Enhanced Extinction of Phobias and Post-Traumatic Stress.
AB  - Virtual reality (VR) refers to an advanced technological communication interface
      in which the user is actively participating in a computer-generated 3-dimensional
      virtual world that includes computer sensory input devices used to simulate real
      world interactive experiences. VR has been used within psychiatric treatment for
      anxiety disorders, particularly specific phobias and post-traumatic stress
      disorder, given several advantages that VR provides for use within treatment for
      these disorders. Exposure therapy for anxiety disorder is grounded in fear
      conditioning models, in which extinction learning involves the process through
      which conditioned fear responses decrease or are inhibited. The present review
      will provide an overview of extinction training and anxiety disorder treatment,
      advantages for using VR within extinction training, a review of the literature
      regarding the effectiveness of VR within exposure therapy for specific phobias
      and post-traumatic stress disorder, and limitations and future directions of the
      extant empirical literature.

PMID- 28512695
TI  - Arsenic Induces Thioredoxin 1 and Apoptosis in Human Liver HHL-5 Cells.
AB  - To further characterize the mechanisms underlying liver toxicity induced by
      arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and
      the apoptotic signaling pathways in human liver HHL-5 cells. The cells were
      treated with 0, 2, 5, and 10 MUM of sodium arsenite for 24 h, and the changes of
      Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis
      were examined. A concentration-dependent increase in mRNA and protein levels of
      Trx1 and TrxR1 was observed in arsenic-treated cells. Intracellular ROS levels
      and apoptosis were also significantly increased in a concentration-dependent
      manner. In line with this, protein levels of Bax and cytochrome C were increased
      and Bcl-2 was decreased by arsenic treatments. Increases in caspase 3 activity
      were observed. These results indicate that Trx is involved in arsenic-induced
      liver cell injury, probably through the apoptotic signaling pathway. However,
      further studies are needed to elucidate on these findings.

PMID- 28512697
TI  - Utilization of Genetic Counseling after Direct-to-Consumer Genetic Testing:
      Findings from the Impact of Personal Genomics (PGen) Study.
AB  - Direct-to-consumer personal genomic testing (DTC-PGT) results lead some
      individuals to seek genetic counseling (GC), but little is known about these
      consumers and why they seek GC services. We analyzed survey data pre- and post
      PGT from 1026 23andMe and Pathway Genomics customers. Participants were mostly
      white (91%), female (60%), and of high socioeconomic status (80% college
      educated, 43% household income of >=$100,000). After receiving PGT results, 43
      participants (4%) made or planned to schedule an appointment with a genetic
      counselor; 390 (38%) would have used in-person GC had it been available. Compared
      to non-seekers, GC seekers were younger (mean age of 38 vs 46 years), more
      frequently had children <18 (26% vs 16%), and were more likely to report previous
      GC (37% vs 7%) and genetic testing (30% vs 15%). In logistic regression analysis,
      seeking GC was associated with previous GC use (OR = 6.5, CI = 3.1-13.8), feeling
      motivated to pursue DTC-PGT for health reasons (OR = 4.3, CI = 1.8-10.1), fair or
      poor self-reported health (OR = 3.1, CI = 1.1-8.3), and self-reported uncertainty
      about the results (OR = 1.8, CI = 1.1-2.7). These findings can help GC providers
      anticipate who might seek GC services and plan for clinical discussions of DTC
      PGT results.

PMID- 28512698
TI  - Repair of the pronator quadratus after volar plate fixation in distal radius
      fractures: a systematic review.
AB  - To position the volar plate on the distal radius fracture site, the pronator
      quadratus muscle needs to be detached from its distal and radial side and lifted
      for optimal exposure to the fracture site. Although the conventional approach
      involves repair of the pronator quadratus, controversy surrounds the merits of
      this repair. The purpose of this study was to compare the functional outcomes of
      patients with distal radius fractures treated with pronator quadratus repair
      after volar plate fixation versus no pronator quadratus repair. A systematic
      search was conducted in Medline, EMBASE and the Cochrane Central Register of
      Controlled Trials, on 23 July 2015. All studies comparing pronator quadratus
      repair with no pronator quadratus repair in adult patients undergoing volar plate
      fixation for distal radius fractures were included. The primary outcome was the
      Disability of the Arm, Shoulder and Hand (DASH) score at 12 months. Secondary
      outcomes included range of motion, grip strength, post-operative pain and
      complications. A total of 169 patients were included, of which 95 underwent
      pronator quadratus repair, while 74 patients underwent no pronator quadratus
      repair. At 12 months follow-up no statistically significant differences in DASH
      scores and range of motion were observed between pronator quadratus repair and no
      repair. Moreover, post-operative pain and complication rates were similar between
      both groups. At 12 months of follow-up, we do not see any advantages of pronator
      quadratus repair after volar plate fixation in the distal radius. However, a
      definitive conclusion cannot be drawn from this systematic review due to a lack
      of available evidence.

PMID- 28512700
TI  - Use of insulin glargine and cancer incidence in Scotland: a study from the
      Scottish Diabetes Research Network Epidemiology Group.

PMID- 28512699
TI  - An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban
      Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in
      Healthy Adults.
AB  - BACKGROUND: Edoxaban is an orally active, direct factor Xa inhibitor indicated to
      reduce the risk of stroke and systemic embolism in non-valvular atrial
      fibrillation and for the treatment of venous thromboembolism. OBJECTIVES: This
      study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60
      mg tablet crushed and administered via a nasogastric tube in a water suspension
      or orally mixed in apple puree. METHODS: This phase 1, open-label, crossover
      study randomized 30 healthy adults to receive three edoxaban treatment regimens
      (oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered
      via a nasogastric tube or orally in apple puree) in one of six treatment
      sequences. RESULTS: Total edoxaban exposure was similar between the intact and
      crushed tablet regimens (mean area under the plasma concentration-time curve from
      time zero to infinity: whole tablet, 2132 ng.h/mL; nasogastric tube, 2021
      ng.h/mL; apple puree, 2076 ng.h/mL). Mean maximum plasma concentration, area
      under the plasma concentration-time curve from time zero to the time of the last
      measurable concentration, terminal half-life, and apparent total body clearance
      values were also similar. Time to maximum plasma concentration was significantly
      shorter for the nasogastric tube suspension and apple puree vs. the whole tablet
      [Hodges-Lehmann estimate of median difference (90% confidence interval): -0.75 (
      1.25, -0.28); p = 0.0003 and -0.62 (-0.99, -0.26); p = 0.0024, respectively]. The
      maximum plasma concentation, area under the plasma concentration-time curve from
      time zero to infinity, and area under the plasma concentration-time curve from
      time zero to the time of the last measurable concentration were similar between
      treatment regimens; 90% confidence interval of the geometric least-squares means
      ratios were within the predefined 80-125% bioequivalence criterion. The safety
      and tolerability of edoxaban did not differ between treatment regimens.
      CONCLUSION: The results support the use of edoxaban tablets crushed and
      administered either via a nasogastric tube or orally mixed in apple puree in
      patients who are unable to swallow solid oral dose formulations.

PMID- 28512701
TI  - Estimation of 3D Ground Reaction Force Using Nanocomposite Piezo-Responsive Foam
      Sensors During Walking.
AB  - This paper describes a method for the estimation of the 3D ground reaction force
      (GRF) during human walking using novel nanocomposite piezo-responsive foam (NCPF)
      sensors. Nine subjects (5 male, 4 female) walked on a force-instrumented
      treadmill at 1.34 m/s for 120 s each while wearing a shoe that was instrumented
      with four NCPF sensors. GRF data, measured via the treadmill, and sensor data,
      measured via the NCPF inserts, were used in a tenfold cross validation process to
      calibrate a separate model for each individual. The calibration model estimated
      average anterior-posterior, mediolateral and vertical GRF with mean average
      errors (MAE) of 6.52 N (2.14%), 4.79 N (6.34%), and 15.4 N (2.15%), respectively.
      Two additional models were created using the sensor data from all subjects and
      subject demographics. A tenfold cross validation process for this combined data
      set resulted in models that estimated average anterior-posterior, mediolateral
      and vertical GRF with less than 8.16 N (2.41%), 6.63 N (7.37%), and 19.4 N
      (2.31%) errors, respectively. Intra-subject estimates based on the model had a
      higher accuracy than inter-subject estimates, likely due to the relatively small
      subject cohort used in creating the model. The novel NCPF sensors demonstrate the
      ability to accurately estimate 3D GRF during human movement outside of the
      traditional biomechanics laboratory setting.

PMID- 28512702
TI  - An Intracardiac Soft Robotic Device for Augmentation of Blood Ejection from the
      Failing Right Ventricle.
AB  - We introduce an implantable intracardiac soft robotic right ventricular ejection
      device (RVED) for dynamic approximation of the right ventricular (RV) free wall
      and the interventricular septum (IVS) in synchrony with the cardiac cycle to
      augment blood ejection in right heart failure (RHF). The RVED is designed for
      safe and effective intracardiac operation and consists of an anchoring system
      deployed across the IVS, an RV free wall anchor, and a pneumatic artificial
      muscle linear actuator that spans the RV chamber between the two anchors. Using a
      ventricular simulator and a custom controller, we characterized ventricular
      volume ejection, linear approximation against different loads and the effect of
      varying device actuation periods on volume ejection. The RVED was then tested in
      vivo in adult pigs (n = 5). First, we successfully deployed the device into the
      beating heart under 3D echocardiography guidance (n = 4). Next, we performed a
      feasibility study to evaluate the device's ability to augment RV ejection in an
      experimental model of RHF (n = 1). RVED actuation augmented RV ejection during
      RHF; while further chronic animal studies will provide details about the efficacy
      of this support device. These results demonstrate successful design and
      implementation of the RVED and its deployment into the beating heart. This soft
      robotic ejection device has potential to serve as a rapidly deployable system for
      mechanical circulatory assistance in RHF.

PMID- 28512703
TI  - Metal homeostasis in bacteria: the role of ArsR-SmtB family of transcriptional
      repressors in combating varying metal concentrations in the environment.
AB  - Bacterial infections cause severe medical problems worldwide, resulting in
      considerable death and loss of capital. With the ever-increasing rise of
      antibiotic-resistant bacteria and the lack of development of new antibiotics,
      research on metal-based antimicrobial therapy has now gained pace. Metal ions are
      essential for survival, but can be highly toxic to organisms if their
      concentrations are not strictly controlled. Through evolution, bacteria have
      acquired complex metal-management systems that allow them to acquire metals that
      they need for survival in different challenging environments while evading metal
      toxicity. Metalloproteins that controls these elaborate systems in the cell, and
      linked to key virulence factors, are promising targets for the anti-bacterial
      drug development. Among several metal-sensory transcriptional regulators, the
      ArsR-SmtB family displays greatest diversity with several distinct metal-binding
      and nonmetal-binding motifs that have been characterized. These prokaryotic
      metolloregulatory transcriptional repressors represses the expression of operons
      linked to stress-inducing concentrations of metal ions by directly binding to the
      regulatory regions of DNA, while derepression results from direct binding of
      metal ions by these homodimeric proteins. Many bacteria, e.g., Mycobacterium
      tuberculosis, Bacillus anthracis, etc., have evolved to acquire multiple metal
      sensory motifs which clearly demonstrate the importance of regulating
      concentrations of multiple metal ions. Here, we discussed the mechanisms of how
      ArsR-SmtB family regulates the intracellular bioavailability of metal ions both
      inside and outside of the host. Knowledge of the metal-challenges faced by
      bacterial pathogens and their survival strategies will enable us to develop the
      next generation drugs.

PMID- 28512704
TI  - Pseudomonas aeruginosa Inhibits the Growth of Scedosporium and Lomentospora In
      Vitro.
AB  - In vitro bacterial-fungal interaction studies in cystic fibrosis (CF) have mainly
      focused on interactions between bacteria and Candida. Here we investigated the
      effect of Pseudomonas aeruginosa on the growth of Scedosporium/Lomentospora spp.
      Standard suspensions of P. aeruginosa (16 non-mucoid and nine mucoid isolates)
      were dropped onto paper disks, placed on lawns of Lomentospora prolificans
      (formerly Scedosporium prolificans) strain WM 14.140 or Scedosporium aurantiacum
      strain WM 11.78 on solid agar. The median inhibitory activity (mIz) was
      calculated for each fungal-bacterial combination. As a group, mIz values for non
      mucoid phenotype P. aeruginosa strains were significantly lower than those for
      mucoid strains (P < 0.001); 14/16 (87.5%) non-mucoid strains had mIz <1.0 against
      both fungi versus just 3/9 mucoid strains (33.4%) (P = 0.01). One non-mucoid
      (PA14) and one mucoid (CIDMLS-PA-28) P. aeruginosa strain effecting inhibition
      were selected for further studies. Inhibition of both L. prolificans and S.
      aurantiacum by these strains was confirmed using the XTT (2,3-bis(2-methoxy-4
      nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide)
      reduction assay. Following incubation with XTT, inhibition of fungal growth was
      determined as the ratio of absorbance in liquid culture with Pseudomonas to that
      in control fungal cultures. An absorbance ratio of <1.0 consistent with bacterial
      inhibition of fungal growth was observed for all four P. aeruginosa-fungal
      combinations (P < 0.05). Fluorescence microscopy, subsequent to co-culture of
      either fungal isolate with P. aeruginosa strain PA14 or CIDMLS-PA-28 revealed
      poorly formed hyphae, compared with control fungal cultures. P. aeruginosa
      inhibits growth of L. prolificans and S. aurantiacum in vitro, with non-mucoid
      strains more commonly having an inhibitory effect. As P. aeruginosa undergoes
      phenotype transitions from non-mucoid to the mucoid form with progression of CF
      lung disease, this balance may influence the appearance of Scedosporium fungi in
      the airways.

PMID- 28512705
TI  - Predicting fecal coliform using the interval-to-interval approach and SWAT in the
      Miyun watershed, China.
AB  - Pathogens in manure can cause waterborne-disease outbreaks, serious illness, and
      even death in humans. Therefore, information about the transformation and
      transport of bacteria is crucial for determining their source. In this study, the
      Soil and Water Assessment Tool (SWAT) was applied to simulate fecal coliform
      bacteria load in the Miyun Reservoir watershed, China. The data for the fecal
      coliform were obtained at three sampling sites, Chenying (CY), Gubeikou (GBK),
      and Xiahui (XH). The calibration processes of the fecal coliform were conducted
      using the CY and GBK sites, and validation was conducted at the XH site. An
      interval-to-interval approach was designed and incorporated into the processes of
      fecal coliform calibration and validation. The 95% confidence interval of the
      predicted values and the 95% confidence interval of measured values were
      considered during calibration and validation in the interval-to-interval
      approach. Compared with the traditional point-to-point comparison, this method
      can improve simulation accuracy. The results indicated that the simulation of
      fecal coliform using the interval-to-interval approach was reasonable for the
      watershed. This method could provide a new research direction for future model
      calibration and validation studies.

PMID- 28512707
TI  - Geochemistry and sources of fluoride and nitrate contamination of groundwater in
      Lar area, south Iran.
AB  - Groundwater quality in bone-dry and semiarid areas of Iran is decreasing because
      of contaminants from natural origins and anthropogenic sources. Among many
      harmful contaminants, nitrate and fluoride ions are more common. This study was
      carried out with the aim of determining geochemical processes controlling
      chemistry of groundwater with special reference to nitrate and fluoride
      enrichment in groundwater in Lar plain aquifer, south of Iran. Groundwater
      samples were collected from 17 sites and analyzed for main constituents (Na, K,
      Ca, Mg, Cl, SO42-, HCO3-, F-, and NO3-). Composite diagram, saturation indices
      calculation, and multivariate analysis techniques including cluster and factor
      analyses were employed in evaluating groundwater quality. The EC ranges from
      8793.87 to 13,345.00 MUS/cm in wet season and from 9621.59 to 12,640.00 MUS/cm in
      dry season. Fluoride amounts range between 0.59 and 3.92 mg/L. Nitrate
      concentrations range between 1.47 and 70.66 mg/L. Results indicate that
      dissolution-precipitation of carbonate and evaporate minerals, evaporation (in
      terms of agricultural water return), and opposite ion interchange are the main
      processes that determine groundwater chemistry. It seems that fluoride has a
      natural origin and the equilibrium reaction between fluorite and calcite is very
      significant to control fluoride concentration level in water. Vertical variation
      of nitrate concentration and distribution of agricultural areas have indicated
      that nitrate originated from nitrogenous inorganic fertilizers used during
      irrigation periods. The results also indicate that denitrification takes place in
      the aquifer and that nitrate decline is not only a function of dilution but also
      a process of denitrification.

PMID- 28512706
TI  - Cyanides in the environment-analysis-problems and challenges.
AB  - Cyanide toxicity and their environmental impact are well known. Nevertheless,
      they are still used in the mining, galvanic and chemical industries. As a result
      of industrial activities, cyanides are released in various forms to all elements
      of the environment. In a natural environment, cyanide exists as cyanogenic
      glycosides in plants seeds. Too much consumption can cause unpleasant side
      effects. However, environmental tobacco smoke (ETS) is the most common source of
      cyanide. Live organisms have the ability to convert cyanide into less toxic
      compounds excreted with physiological fluids. The aim of this paper is to review
      the current state of knowledge on the behaviour of cyanide in the environment and
      its impact on the health and human life.

PMID- 28512709
TI  - Influence of low-temperature combustion and dimethyl ether-diesel blends on
      performance, combustion, and emission characteristics of common rail diesel
      engine: a CFD study.
AB  - Due to presence of more oxygen, absence of carbon-carbon (C-C) bond in chemical
      structure, and high cetane number of dimethyl ether (DME), pollution from DME
      operated engine is less compared to diesel engine. Hence, the DME can be a
      promising alternative fuel for diesel engine. The present study emphasizes the
      effect of various exhaust gas recirculation (EGR) rates (0-20%) and DME/Diesel
      blends (0-20%) on combustion characteristics and exhaust emissions of common rail
      direct injection (CRDI) engine using three-dimensional computational fluid
      dynamics (CFD) simulation. Extended coherent flame model-3 zone (ECFM-3Z) is
      implemented to carry out combustion analysis, and k-xi-f model is employed for
      turbulence modeling. Results show that in-cylinder pressure marginally decreases
      with employing EGR compared to without EGR case. As EGR rate increases, nitrogen
      oxide (NO) formation decreases, whereas soot increases marginally. Due to better
      combustion characteristics of DME, indicated thermal efficiency (ITE) increases
      with the increases in DME/diesel blend ratio. Adverse effect of EGR on efficiency
      for blends is less compared to neat diesel, because the anoxygenated region
      created due to EGR is compensated by extra oxygen present in DME. The trade-off
      among NO, soot, carbon monoxide (CO) formation, and efficiency is studied by
      normalizing the parameters. Optimum operating condition is found at 10% EGR rate
      and 20% DME/diesel blend. The maximum indicated thermal efficiency was observed
      for DME/diesel ratio of 20% in the present range of study. Obtained results are
      validated with published experimental data and found good agreement.

PMID- 28512708
TI  - Titanium dioxide-based sonophotocatalytic mineralization of bisphenol A and its
      intermediates.
AB  - In this study, bisphenol A (BPA) removal by sonophotocatalysis coupled with
      commercially available titanium dioxide (TiO2, P25) was assessed in batch tests
      using energy-based advanced oxidation combining ultrasound (US) and ultraviolet
      (UV). The kinetics of BPA removal were systematically evaluated by changing
      operational parameters, such as US frequency and power, mechanical stirring
      speed, and temperature, but also comparison of single and coupled systems under
      the optimum US conditions (35 kHz, 50 W, 300 rpm stirring speed, and 20  degrees
      C). The combination of US/UV/P25 exhibited the highest BPA removal rate (28.0 *
      10-3 min-1). In terms of the synergy index, the synergistic effect of
      sonophotocatalysis was found to be 2.2. This indicated that sonophotocatalysis
      has a considerably higher removal efficiency than sonocatalysis or
      photocatalysis. The removal of BPA was further investigated to identify BPA
      byproducts and intermediates using high-performance liquid chromatography-mass
      spectrometry. Five main intermediates were formed during sonophotocatalytic
      degradation, and complete removal of BPA and its intermediates was obtained after
      3 h of operation. The degradation pathway of BPA by sonophotocatalysis was also
      elucidated.

PMID- 28512711
TI  - Environmental Kuznets curve for EU agriculture: empirical evidence from new
      entrant EU countries.
AB  - The present work examines the intertemporal causal relationship between
      environmental damage from carbon emissions released by agriculture per 1000 ha of
      utilized agriculture area and economic performance in the sector of agriculture
      as described by net value added per capita. The autoregressive distributed lag
      bounds testing approach is employed to examine this linkage, for three new
      entrant EU countries, namely, Bulgaria, Czech Republic, and Hungary. The
      environmental Kuznets hypothesis is confirmed in the long run for Bulgaria and
      Czech Republic while in the short run is validated only for the case of Czech
      Republic. The results indicate that the adoption of environment-friendly farming
      practices and crops' selection does not secure simultaneous high economic and
      environmental performance at least in the short run for our sample countries and
      also in the long run for Hungary necessitating the modification of the agro
      environmental measures adopted to make those two targets complementary and not
      mutually exclusive for a farmer.

PMID- 28512710
TI  - Effects of coexisting BDE-47 on the migration and biodegradation of BDE-99 in
      river-based aquifer media recharged with reclaimed water.
AB  - Two prominent polybrominated diphenyl ether (PBDE) congeners have been included
      in the persistent organic pollutant list, 2,2',4,4',5-tetrabromodiphenyl ether
      (BDE-99) and 2,2,4,4'-tetrabromodiphenyl ether (BDE-47), which have been detected
      in treated municipal wastewater, river water, and sediments in China. A lab-scale
      column experiment was established to investigate the effects of the competitive
      sorption of BDE-47 on BDE-99 biodegradation and migration in two types of river
      based aquifer soils during groundwater recharge with reclaimed water. Two types
      of recharge columns were used, filled with either silty clay (SC) or black carbon
      amended silty clay (BCA). The decay rate constants of BDE-99 in the BCA and SC
      systems were 0.186 and 0.13 m-1 in the single-solute system and 0.128 and 0.071 m
      1 in the binary-solute system, respectively, showing that the decay of BDE-99 was
      inhibited by the coexistence of BDE-47. This was particularly evident in the SC
      system because the higher hydrophobicity of BDE-99 determined the higher affinity
      and competition for sorption sites onto black carbon. The biodegradation of BDE
      99 was suppressed by the coexistence of BDE-47, especially in the SC system.
      Lesser-brominated congeners (BDE-47 and BDE-28) and higher-brominated congeners
      (BDE-100, BDE-153, BDE-154, and BDE-183) were generated in the four recharge
      systems, albeit at different ratios. Bacterial biodiversity was influenced by the
      presence of BDE-47 in the SC system, while it had no significant effect on the
      BCA system, because the high sorption capacity of black carbon on the hydrophobic
      PBDEs effectively reduced their toxicity. The ranking order of the most abundant
      classes changed markedly due to the coexistence of BDE-47 in both the SC and BCA
      systems. The ranking order of the most abundant genera changed from Azospira,
      Methylotenera, Desulfovibrio, Methylibium, and Bradyrhizobium to Halomonas,
      Hyphomicrobium, Pseudomonas, Methylophaga, and Shewanella, which could be
      involved in PBDE degradation.

PMID- 28512712
TI  - Post-Translational Tubulin Modifications in Human Astrocyte Cultures.
AB  - The cytoskeletal protein tubulin plays an integral role in the functional
      specialization of many cell types. In the central nervous system, post
      translational modifications and the expression of specific tubulin isotypes in
      neurons have been analyzed in greater detail than in their astrocytic
      counterparts. In this study, we characterized post-translational specifications
      of tubulin in human astrocytes using the normal human astrocyte (NHA; Lonza)
      commercial cell line of fetal origin. Immunocytochemical techniques were
      implemented in conjunction with confocal microscopy to image class III beta
      tubulin (betaIII-tubulin), acetylated tubulin, and polyglutamylated tubulin using
      fluorescent antibody probes. Fluorescent probe intensity differences and
      colocalization were quantitatively assessed with the 'EBImage' package for the
      statistical programming language R. Colocalization analysis revealed that,
      although both acetylated tubulin and polyglutamylated tubulin showed a high
      degree of correlation with betaIII-tubulin, the correlation with acetylated
      tubulin was stronger. Quantification and statistical analysis of fluorescence
      intensity demonstrated that the fluorescence probe intensity ratio for acetylated
      tubulin/betaIII-tubulin was greater than the ratio for polyglutamylated
      tubulin/betaIII-tubulin. The open source GEODATA set GSE819950, comprising RNA
      sequencing data for the NHA cell line, was mined for the expression of enzymes
      responsible for tubulin modifications. Our analysis uncovered greater expression
      at the mRNA level for enzymes reported to function in acetylation and
      deacetylation as compared to enzymes implicated in glutamylation and
      deglutamylation. Taken together, the results represent a step toward unraveling
      the tubulin isotypic expression profile and post-translational modification
      patterns in astrocytes during human brain development.

PMID- 28512713
TI  - Matairesinol Suppresses Neuroinflammation and Migration Associated with Src and
      ERK1/2-NF-kappaB Pathway in Activating BV2 Microglia.
AB  - Chronic neuroinflammation is a pathological feature of neurodegenerative
      diseases. Inhibition of microglia-mediated neuroinflammation might be a potential
      strategy for neurodegeneration. Matairesinol, a dibenzylbutyrolactone plant
      lignan, presents in a wide variety of foodstuffs. It has been found to possess
      anti-angiogenic, anti-oxidative, anti-cancer and anti-fungal activities. In the
      present study, we investigated the anti-neuroinflammation effects of matairesinol
      on lipopolysaccharide (LPS)-induced BV2 microglia cells and the related molecular
      mechanisms. The results showed that matairesinol inhibited microglia activation
      by reducing the production of nitric oxide, the expression of inducible nitric
      oxide synthase and cyclooxygenase-2 in a concentration-dependent manner (6.25,
      12.5, 25 MUM). In the molecular signaling pathway, LPS-induced nuclear factor
      kappa B (NF-kappaB) transcriptional activity and translocation into the nucleus
      were remarkably suppressed by matairesinol through the inhibition of the
      extracellular signal-regulated kinase (ERK)1/2 signal transduction pathways, but
      not p38 MAPK or c-jun N-terminal kinase (JNK). Meanwhile, matairesinol also
      blocked LPS-mediated microglia migration and this was associated with inhibition
      of LPS-induced Src phosphorylation as well as Src expression in a concentration
      dependent manner. Taken together, these results suggest that matairesinol
      inhibited inflammatory response and migration in LPS-induced BV2 microglia, and
      the mechanisms may be associated with the NF-kappaB activation and modulation of
      Src pathway.

PMID- 28512715
TI  - Management of rainwater harvesting and its impact on the health of people in the
      Middle East: case study from Yatta town, Palestine.
AB  - Water-related diseases are a primary problem in Palestine where many residents
      revert to harvested rainwater as their primary water source due to water
      shortages within the area. From an environmental engineering perspective, it is
      already well known that certain situations (e.g., cross contamination) reduce
      drinking water quality and ultimately cause diseases in a population. In this
      study, we investigated the social practices and situations that may lead to lower
      disease occurrence. Towards this goal, we surveyed 382 residents in Yatta to
      collect data on the water-related diseases that they experienced and the specific
      situations that might affect the disease occurrences such as the residents'
      practices (i) for maintaining a high quality of cistern water, (ii) for
      maintaining the environment around the cistern, and (iii) for managing the
      wastewater. In addition, we measured the physicochemical and microbiological
      parameters in cisterns to support the qualitative survey data. The measured
      parameters, including turbidity, salinity, free available chlorine, total
      Coliforms, and fecal Coliforms, were above Palestinian Standard Institution (PSI)
      and World Health Organization (WHO) guideline levels, suggesting a potential
      infectious hazard. The poor quality of the water was also observed by residents
      based on change in taste and by visually noting floating impurities, turbidity,
      and green coloration. Survey results showed that observations of the poor quality
      in cisterns and surrounding environment had statistically significant correlation
      with most of the water-related diseases. Additionally, frequently emptying the
      septic tank contributes to improving the observed water qualities. Therefore,
      residents should be encouraged to continue to observe the water quality in the
      cistern, improve the surrounding environment of cistern, and empty their septic
      tank frequently, to keep the water diseases away from their households.

PMID- 28512716
TI  - Clint M. Alfaro wins ABC Best Paper Award.

PMID- 28512714
TI  - Comparison of the diagnostic accuracy of PET/MRI to PET/CT-acquired FDG brain
      exams for seizure focus detection: a prospective study.
AB  - BACKGROUND: There is great interest in positron emission tomography
      (PET)/magnetic resonance (MR) as a clinical tool due to its capacity to provide
      diverse diagnostic information in a single exam. OBJECTIVE: The goal of this exam
      is to compare the diagnostic accuracy of PET/MR-acquired [F-18]2-fluoro-2
      deoxyglucose (FDG) brain exams to that of PET/CT with respect to identifying
      seizure foci in children with localization-related epilepsy. MATERIALS AND
      METHODS: Institutional Review Board approval and informed consent were obtained
      for this Health Insurance Portability and Accountability Act-compliant,
      prospective study. All patients referred for clinical FDG-PET/CT exams of the
      brain at our institution for a diagnosis of localization-related epilepsy were
      prospectively recruited to undergo an additional FDG-PET acquisition on a tandem
      PET/MR system. Attenuation-corrected FDG images acquired at PET/MR and PET/CT
      were interpreted independently by five expert readers. Readers were blinded to
      the scanner used for acquisition and attenuation correction as well as all other
      clinical and imaging data. A Likert scale scoring system (1-5) was used to assess
      image quality. The locale of seizure origin determined at multidisciplinary
      epilepsy surgery work rounds was considered the reference standard. Non
      inferiority testing for paired data was used to compare the diagnostic accuracy
      of PET/MR to that of PET/CT. RESULTS: The final study population comprised 35
      patients referred for a diagnosis of localization-related epilepsy (age range: 2
      19 years; median: 11 years; 21 males, 14 females). Image quality did not differ
      significantly between the two modalities. The accuracy of PET/MR was not inferior
      to that of PET/CT for localization of a seizure focus (P=0.017). CONCLUSION: The
      diagnostic accuracy of FDG-PET images acquired on a PET/MR scanner and generated
      using MR-based attenuation correction was not inferior to that of PET images
      processed by traditional CT-based correction.

PMID- 28512717
TI  - Infrared laser ablation sample transfer of tissue DNA for genomic analysis.
AB  - Infrared (IR) laser ablation was used to remove material from tissue sections
      mounted on microscope slides, with subsequent capture in a solvent-containing
      microcentrifuge tube. Experiments conducted with a 3200-bp double-stranded
      plasmid DNA template demonstrated IR-laser ablation transfer of intact DNA. The
      transfer efficiency and the molecular integrity of the captured DNA were
      evaluated using Sanger sequencing, gel electrophoresis, and fluorimetric
      analysis. The plasmid DNA was reproducibly transferred with an efficiency of 59
      +/- 3% at laser fluences of between 10 and 20 kJ/m2 at a wavelength of 3 MUm. IR
      laser ablation sample transfer was then used to ablate and capture DNA from 50
      MUm-thick rat brain and kidney tissue sections. DNA was extracted from the
      captured material using five commercial DNA extraction kits that employed
      significantly divergent methodologies, with all kits recovering sufficient DNA
      for successful amplification by polymerase chain reaction (PCR). Four sets of
      primers were employed, targeting one region of the CYP 11b2 gene (376 bp) and
      three different regions of the Snn1g gene (298, 168, and 281 bp). The PCR results
      were not consistently reliable when using unpurified ablation samples; however,
      after extraction, all samples produced PCR products of the expected size. This
      work expands the sampling capabilities of IR laser ablation, demonstrating that
      DNA can be isolated from tissue samples for genomic assays. Due to the small size
      of the ablation regions (1 mm2), this technique will be useful for sampling
      discrete cell populations from tissue sections. Graphical abstract Infrared laser
      ablation transfer of intact DNA from a tissue section.

PMID- 28512718
TI  - Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended
      Release Tablet Formulation Using Urinary Pharmacokinetic Data.
AB  - PURPOSE: To develop and validate a Level A in vitro-in vivo correlation (IVIVC)
      for potassium chloride extended-release (ER) formulations. METHODS: Three
      prototype ER formulations of potassium chloride with different in vitro release
      rates were developed and their urinary pharmacokinetic profiles were evaluated in
      healthy subjects. A mathematical model between in vitro dissolution and in vivo
      urinary excretion, a surrogate for measuring in vivo absorption, was developed
      using time-scale and time-shift parameters. The IVIVC model was then validated
      based on internal and external predictability. RESULTS: With the established
      IVIVC model, there was a good correlation between the observed fraction of dose
      excreted in urine and the time-scaled and time-shifted fraction of the drug
      dissolved, and between the in vitro dissolution time and the in vivo urinary
      excretion time for the ER formulations. The percent prediction error (%PE) on
      cumulative urinary excretion over the 24 h interval (Ae0-24h) and maximum urinary
      excretion rate (Rmax) was less than 15% for the individual formulations and less
      than 10% for the average of the two formulations used to develop the model.
      Further, the %PE values using external predictability were below 10%.
      CONCLUSIONS: A novel Level A IVIVC was successfully developed and validated for
      the new potassium chloride ER formulations using urinary pharmacokinetic data.
      This successful IVIVC may facilitate future development or manufacturing changes
      to the potassium chloride ER formulation.

PMID- 28512719
TI  - Hypoplastic Left Heart Syndrome with Congenital Complete Heart Block.
AB  - Congenital complete atrioventricular block (CCAVB) is a rare condition with an
      incidence of 1 of 20,000 live births. Hypoplastic left heart syndrome (HLHS)
      occurs more frequently than CCAVB and occurs in 1 of 5000 live births. HLHS in
      association with CCAVB is exceedingly rare. In this report, we describe a rare
      case of HLHS and CCAVB diagnosed in utero. Postnatal diagnosis, management and
      outcome are presented as well as review of the medical literature.

PMID- 28512720
TI  - Pacing Induced Ventricular Dysfunction in a Child: Improvement with Reduction in
      Paced Rate.
AB  - Right ventricular (RV) pacing can be associated with impairment of left
      ventricular (LV) function due to electrical dyssynchrony and myocardial
      remodeling (Janousek et al. in J Cardiovasc Electrophysiol 15:470-474, 2004). RV
      pacing induced ventricular dysfunction is reversible by techniques such as
      biventricular pacing and LV apical or LV free wall pacing or turning the
      pacemaker off which have all been shown to restore synchrony and improve left
      ventricular function (Janousek et al. in J Cardiovasc Electrophysiol 15:470-474,
      2004; Geldorp et al. in Heart Fail Rev 16:305-314, 2011). We describe an infant
      with RV-pacing induced cardiomyopathy who improved when the pacing rate was
      reduced thus demonstrating the relationship between pacing rate and development
      of LV dysfunction.

PMID- 28512721
TI  - Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children
      with Kawasaki Disease and Transient Coronary Abnormalities.
AB  - There is evidence for premature atherosclerosis and systemic arterial stiffening
      during follow-up of children with Kawasaki disease (KD) and coronary artery
      abnormalities (CAA). Moreover, patients with KD may also have subclinical
      myocardial involvement and inhomogeneous ventricular repolarization. The
      inhomogeneous ventricular repolarization manifests as increased QT dispersion on
      electrocardiography. There is a paucity of studies in endothelial dysfunction and
      QT dispersion in children with KD and transient CAA. Twenty children with KD and
      transient CAA were studied at least 1 year after resolution of CAA. Mean follow
      up period between KD onset and enrolment in the study was 53.7 months. Twenty age
      and sex-matched controls were enrolled. High-resolution B-mode ultrasonography
      was used to analyze brachial artery dilatation in response to reactive hyperemia
      (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery
      intima-media thickness (cIMT) and stiffness index were calculated. The difference
      between maximum and minimum QTc intervals on 12 lead electrocardiogram was
      calculated as QTc dispersion (QTcd). No statistically significant difference was
      noted in percent flow-mediated dilatation of brachial arteries in response to
      reactive hyperemia between cases (13.31 +/- 10.41%) and controls (12.86 +/-
      7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was
      14.88 +/- 12.03%. Mean cIMT was similar in cases (0.036 +/- 0.015 cm) and
      controls (0.035 +/- 0.076 cm; p = 0.791). No statistically significant difference
      between groups was observed in mean QTcd values (0.057 +/- 0.018 s vs. 0.059 +/-
      0.015 s in controls, p = 0.785). No evidence of significant endothelial
      dysfunction or increased QT dispersion in patients with KD and transient coronary
      artery abnormalities was found in our cohort when studied at a mean follow-up of
      53.7 months. This is reassuring, and indicates that risk of subclinical
      atherosclerosis and myocarditis in a subset of children with KD and transient
      coronary artery abnormalities is not significant.

PMID- 28512722
TI  - Status of cardiovascular PET radiation exposure and strategies for reduction: An
      Information Statement from the Cardiovascular PET Task Force.
AB  - Cardiovascular positron emission tomography (PET) imaging provides high-quality
      visual and quantitative myocardial perfusion and function images. In addition,
      cardiovascular PET can assess myocardial viability, myocardial inflammatory
      disorders such as cardiac sarcoid, and infections of implanted devices including
      pacemakers, ventricular assist devices, and prosthetic heart valves. As with all
      nuclear cardiology procedures, the benefits need to be considered in relation to
      the risks of exposure to radiation. When performed properly, these assessments
      can be obtained while simultaneously minimizing radiation exposure. The purpose
      of this information statement is to present current concepts to minimize patient
      and staff radiation exposure while ensuring high image quality.

PMID- 28512723
TI  - Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and
      assessed through a head-to-head comparison with a conventional single-isotope
      protocol.
AB  - PURPOSE OF THE REPORT: This study aimed at assessing an original low-dose dual
      isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed
      by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope
      procedure. METHODS AND RESULTS: One hundred two patients, referred for a low-dose
      stress-SPECT with Sestamibi (123 +/- 20 MBq) on a CZT camera and for whom a rest
      Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 +/- 5 MBq)
      between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed
      for spill-over and scatter corrections, and uptake differences with stress
      Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual
      isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in
      segments for which a diagnosis of ischemia, infarct, or normal perfusion was
      achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to
      5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not
      warranted. After a further background correction of Tl-201 images, the rest
      stress difference in myocardial uptake was equivalent between dual- and single
      procedures for identifying ischemic segments (respective areas-under-curves: 0.83
      +/- 0.03 and 0.81 +/- 0.03). CONCLUSION: This original dual-isotope procedure
      provides acceptable radiation doses and consistent results, as compared with
      conventional single-isotope.

PMID- 28512724
TI  - Congenital Pulmonary Alveolar Proteinosis: From Birth to Ten-years of Age.
AB  - Pulmonary alveolar proteinosis is a rare lung disease in which lipoproteinaceous
      material accumulates within the alveoli, interfering with gas exchange. The
      disease is classified into congenital, secondary, and acquired. The congenital
      form includes inborn errors of surfactant metabolism, lysinuric protein
      intolerance and mutations in the components of granulocyte-macrophage colony
      stimulating factor receptor. The main symptoms are non-specific. The radiologic
      appearance of pulmonary alveolar proteinosis is bilateral, symmetric and
      perihilar airspace consolidation. Bronchoalveolar lavage is crucial for diagnosis
      of the disease. There is only one ten-year-old patient with diagnosed congenital
      form in Croatia. What makes him different from other children in the world is
      that since the ninth month of his life he has been mechanically ventilated.
      Diagnosis of postnatal alveolar proteinosis should be considered in every infant
      with respiratory distress with diffuse alveolar and interstitial infiltrate.

PMID- 28512725
TI  - Clofibrate as an Adjunct to Phototherapy for Unconjugated Hyperbilirubinemia in
      Term Neonates.
AB  - OBJECTIVE: To evaluate the efficacy of oral clofibrate as an adjunct to
      phototherapy for unconjugated hyperbilirubinemia in term neonates. METHODS: This
      randomized controlled trial was done in the level III neonatal intensive care
      unit (NICU) of a tertiary care hospital. Ninety term neonates with unconjugated
      hyperbilirubinemia with serum bilirubin 15-25 mg/dl were randomized to either
      intervention group (single dose of clofibrate in a dose of 50 mg/kg prior to
      starting phototherapy) or standard care group (only phototherapy). Primary
      outcome was absolute fall in bilirubin by 48 h. Secondary outcomes were duration
      of phototherapy, absolute fall in bilirubin levels at 12, 24, 36, 48 h, need for
      exchange transfusion and incidence of side-effects. RESULTS: After 48 h of
      intervention, significantly lower bilirubin levels were noted in the intervention
      group compared to standard care group with a mean difference of 7 mg/dl (95% CI
      6.7 mg/dl to 7.2 mg/dl). Duration of phototherapy required was less in the
      intervention group compared to standard care group with mean difference of 23.82
      h (95% CI 30.46 h to 17.18 h). Exchange transfusion was needed for 4 neonates in
      the standard care group and none in the intervention group. No side-effects were
      noted with clofibrate. CONCLUSIONS: Single dose clofibrate prior to starting
      phototherapy in term neonates with uncomplicated unconjugated hyperbilirubinemia
      reduces the duration of phototherapy significantly.

PMID- 28512726
TI  - Cutaneous reflex modulation during obstacle avoidance under conditions of normal
      and degraded visual input.
AB  - The nervous system integrates visual input regarding obstacles with limb-based
      sensory feedback to allow an individual to safely negotiate the environment. This
      latter source can include cutaneous information from the foot, particularly in
      the event that limb trajectory is not sufficient and there is an unintended
      collision with the object. However, it is not clear the extent to which cutaneous
      reflexes are modified based on visual input. In this study, we first determined
      if phase-dependent modulation of these reflexes is present when stepping over an
      obstacle during overground walking. We then tested the hypothesis that degrading
      the quality of visual feedback alters cutaneous reflex amplitude in this task.
      Subjects walked and stepped over an obstacle-leading with their right foot-while
      we electrically stimulated the right superficial peroneal nerve at the level of
      the ankle at different phases. Subjects performed this task with normal vision
      and with degraded vision. We found that the amplitude of cutaneous reflexes
      varied based on the phase of stepping over the obstacle in all leg muscles
      tested. With degraded visual feedback, regardless of phase, we found larger
      facilitation of cutaneous reflexes in the ipsilateral biceps femoris-a muscle
      responsible for flexing the knee to avoid the obstacle. Although degrading vision
      caused minor changes in several other muscles, none of these differences reached
      the level of significance. Nonetheless, our results suggest that visual feedback
      plays a role in altering how the nervous system uses other sensory input in a
      muscle-specific manner to ensure safe obstacle clearance.

PMID- 28512728
TI  - Treatment of red tattoo reaction using CO2 laser.

PMID- 28512727
TI  - Variability of high-dose melphalan exposure on oral mucositis in patients
      undergoing prophylactic low-level laser therapy.
AB  - The present study outlines the clinical impact and risk factors of oral mucositis
      in 79 patients with multiple myeloma following high-dose melphalan for autologous
      transplant. All patients underwent daily prophylactic low-level indium gallium
      aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm2, 10 s per
      point) from the beginning of the conditioning regimen up to day +2. Oral
      mucositis assessments were made daily until hospital discharge. For analysis,
      oral mucositis was divided into two groups according to severity: group 1,
      patients with oral mucositis grade <III (n = 71) and group 2, patients with oral
      mucositis grade >=III (n = 8). Univariate logistic models were used to determine
      the risk factors. Patients in group 1 were found to have statistically fewer days
      of oral pain than those in group 2 (3.94 and 6.25 days, respectively, p = 0.014).
      Morphine was required in 75% of patients in group 2, versus 42.25% in group 1 (p
      = 0.06). Risk of severe oral mucositis was associated with higher serum
      creatinine levels (OR = 6.10; 95% CI 1.25-31.60; p = 0.02) and older age (OR =
      1.21; 95% CI 1.05-1.47; p = 0.027). Severe oral mucositis was associated with
      worse clinical outcomes. Older patients and those with renal dysfunction previous
      autologous transplant had the greatest risk for severe oral mucositis despite
      prophylactic laser treatment. Our results highlight the importance of further
      research to define the dose, application time, and number of prophylactic laser
      sessions in those patients with the greatest risk for severe oral mucositis.

PMID- 28512731
TI  - Active Surveillance for Prostate Cancer: How to Do It Right.
AB  - Prostate cancer is the most common malignancy affecting men. There has been a
      nearly 70% increase in new prostate cancer cases, mostly classified as low risk,
      that have been diagnosed in early stages as a consequence of prostate-specific
      antigen (PSA) screening. Data regarding the natural history of this disease
      confirm the clinical insignificance of low-grade prostate cancer, which is
      associated with scant or no metastatic dissemination. Active surveillance is a
      conservative management approach, conducted for those patients with "low-risk" or
      "favorable-risk" disease, which avoids long-term adverse effects on the patient's
      quality of life. It is characterized by a routine protocol of close monitoring
      with digital rectal examination, periodic biopsy, and serial PSA testing. As
      defined by D'Amico, active surveillance is broadly appropriate for men with a
      Gleason score of 6 or less and a PSA level of less than 10 ng/mL. Typically,
      Gleason pattern 3 disease lacks the common genetic aberrancies of a true cancer.
      An essential element of the active surveillance approach is early recognition of
      higher-risk disease, which is diagnosed by systematic biopsy in 30% of patients
      who initiate active surveillance with low-risk disease. Also, a small group of
      patients have molecular alterations that can cause progression to more aggressive
      disease; these men can be switched to immediate treatment if such progression is
      detected. Oncologic outcomes for active surveillance cohorts have shown the long
      term safety of this approach, with a cancer-specific mortality rate of 3% at 10
      to 15 years. In this review of active surveillance for favorable-risk prostate
      cancer, we will discuss the rationality of this approach, the biological evidence
      for employing active surveillance in Gleason pattern 3 and 4 prostate cancer,
      patient selection for active surveillance, clinical trial data on active
      surveillance, and the role of prostate cancer biomarkers and imaging studies
      (MRI) for clinical decision making in patients with low-risk disease.

PMID- 28512730
TI  - Examining the Role of Transmission of Chelonid Alphaherpesvirus 5.
AB  - Marine turtle fibropapillomatosis (FP) is a devastating neoplastic disease
      characterized by single or multiple cutaneous and visceral fibrovascular tumors.
      Chelonid alphaherpesvirus 5 (ChHV5) has been identified as the most likely
      etiologic agent. From 2010 to 2013, the presence of ChHV5 DNA was determined in
      apparently normal skin, tumors and swab samples (ocular, nasal and cloacal)
      collected from 114 olive ridley (Lepidochelys olivacea) and 101 green (Chelonia
      mydas) turtles, with and without FP tumors, on the Pacific coasts of Costa Rica
      and Nicaragua. For nesting olive ridley turtles from Costa Rica without FP, 13.5%
      were found to be positive for ChHV5 DNA in at least one sample, while in
      Nicaragua, all olive ridley turtles had FP tumors, and 77.5% tested positive for
      ChHV5 DNA. For green turtles without FP, 19.8% were found to be positive for
      ChHV5 DNA in at least one of the samples. In turtles without FP tumors, ChHV5 DNA
      was detected more readily in skin biopsies than swabs. Juvenile green turtles
      caught at the foraging site had a higher prevalence of ChHV5 DNA than adults. The
      presence of ChHV5 DNA in swabs suggests a possible route of viral transmission
      through viral secretion and excretion via corporal fluids.

PMID- 28512729
TI  - Protective effects of Nebivolol against interleukin-1beta (IL-1beta)-induced type
      II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13).
AB  - The pathological progression of osteoarthritis (OA) involves degradation of
      articular cartilage matrix. Type II collagen is the main component of cartilage
      matrix, which is degraded by pro-inflammatory cytokines such as IL-1beta mediated
      by MMP-13. Nebivolol, a licensed drug used for the treatment of hypertension in
      clinics, displays its anti-inflammatory capacity in various conditions. However,
      whether Nebivolol has a protective effect on cartilage matrix degradation has not
      been reported before. In this study, we investigated the effects of Nebivolol on
      regulating the expression of MMP-13 and degradation of type II collagen. Our
      results indicate that Nebivolol alleviated the increase in gene expression,
      protein expression, and activity of MMP-13 induced by IL-1beta. Importantly, IL
      1beta strikingly reduced the levels of type II collagen in cell culture
      supernatants, which was reversed by treatment with Nebivolol in a dose-dependent
      manner. Mechanistically, Nebivolol was found to alleviate the increased levels of
      phosphorylated IkappaBalpha and reduced levels of total IkappaBalpha induced by
      IL-1beta, which subsequently mitigated p65 nuclear translocation and the
      transcriptional activity of NF-kappaB. Furthermore, our results indicated that IL
      1beta treatment resulted in a significant increase in expression of the
      transcriptional factor interferon regulatory factor-1 (IRF-1) at both the mRNA
      and protein levels, which was significantly ameliorated by treatment with
      Nebivolol. The combination of these findings suggests that Nebivolol can
      potentially be applied in human OA treatment.

PMID- 28512732
TI  - Decision Making in the Surgical Management of Invasive Breast Cancer-Part 1:
      Lumpectomy, Mastectomy, and Contralateral Prophylactic Mastectomy.
AB  - Several prospective randomized clinical trials conducted internationally have
      proven the safety and survival equivalence of breast-conserving surgery compared
      with mastectomy. Adjuvant radiation is routinely recommended following lumpectomy
      surgery to minimize the risk of local recurrence. Comprehensive breast imaging
      (including bilateral mammography with diagnostic views and ultrasound
      evaluation), in addition to clinical examination, is essential to rule out
      potential contralateral pathology and to optimally characterize the extent of
      disease. These studies are considered standard in the assessment of patient
      eligibility for lumpectomy. MRI of the breast remains controversial as an adjunct
      to determine candidacy for breast conservation, since MRI findings increase
      mastectomy rates without evidence of improved local control; prospective
      randomized clinical trials are underway to define the role of MRI in newly
      diagnosed breast cancer. Recently, the multidisciplinary oncology community has
      adopted a consensus guideline defining "no ink on tumor" as an acceptable
      microscopic margin at lumpectomy; however, post-lumpectomy imaging may be
      necessary to confirm complete removal of all cancer-associated
      microcalcifications, with clinical judgment exercised regarding re-excision for
      close margins. Contralateral prophylactic mastectomy is becoming increasingly
      common in the United States, and patients considering this option must be
      counseled about its lack of a survival benefit, its higher complication rate, and
      the fact that it is risk-reducing but not risk-eliminating.

PMID- 28512733
TI  - A lipidomic cell-based assay for studying drug-induced phospholipidosis and
      steatosis.
AB  - Phospholipidosis and steatosis are two toxic effects, which course with
      overaccumulation of different classes of lipids in the liver. MS-based lipidomics
      has become a powerful tool for the comprehensive determination of lipids. LC-MS
      lipid profiling of HepG2 cells is proposed as an in vitro assay to study and
      anticipate phospholipidosis and steatosis. Cells with and without preincubation
      with a mixture of free fatty acids (FFA; i.e. oleic and palmitic) were exposed to
      a set of well-known steatogenic and phospholipidogenic compounds. The use of FFA
      preloading accelerated the accumulation of phospholipids, thus leading to a
      better discrimination of phospholipidosis, and magnified the lipidomic
      alterations induced by steatogenic drugs. Phospholipidosis was characterized by
      increased levels of phosphatidylcholines, phosphatidylethanolamines,
      phosphatidylserines, and phosphatidylinositols, while steatosis induced
      alterations in FA oxidation and triacylglyceride (TG) synthesis pathways (with
      changes in the levels of FFA, acylcarnitines, monoacylglycerides,
      diacylglycerides, and TG). Interestingly, palmitic and oleic acids incorporation
      into lipids differed. A characteristic pattern was observed in the fold of change
      of particular TG species in the case of steatosis (TG(54:3) > TG(52:2) > TG(50:1)
      > TG(48:0)). Based on the levels of those lipids containing only palmitic and/or
      oleic acid moieties a partial least squares-discriminant analysis model was
      built, which showed good discrimination among nontoxic, phospholipidogenic and
      steatogenic compounds. In conclusion, it has been shown that the use of FFA
      preincubation together with intracellular LC-MS based lipid profiling could be a
      useful approach to identify the potential of drug candidates to induce
      phospholipidosis and/or steatosis.

PMID- 28512734
TI  - Mitral valve aneurysms: Clinical characteristics, echocardiographic
      abnormalities, and possible mechanisms of formation.
AB  - AIMS: Mitral valve aneurysms (MVA) are most frequently associated with
      endocarditis. Echocardiography is the method of choice for diagnosis, and color
      flow imaging is an important, easy method to detect MVA ruptures. We aimed to
      study the clinical and echocardiographic findings and their relation to the
      mechanism of aneurysm formation. METHODS AND RESULTS: We reviewed clinical and
      echocardiographic records of 18 patients during a 17-year period, corresponding
      to 0.02% of the total studies performed at our institution. All patients
      underwent transthoracic echocardiogram (TTE), and all except two underwent
      transesophageal echocardiogram (TEE). The aneurysm was located either on the
      anterior leaflet (16 cases) or on the posterior leaflet (two cases). In seven
      cases, the probable aneurysm formation mechanism was an aortic regurgitant jet
      striking the anterior mitral leaflet. Perforation was present in 17 (94.4%)
      patients, and 10 (55.5%) cases presented more than one aneurysm. No patients
      underwent surgery exclusively because of the echocardiography finding.
      CONCLUSION: Different etiologies and formation mechanisms can occur in MVA.
      Echocardiography plays a fundamental role, providing meticulous examination of
      the mitral valve anatomy and flow. Unlike standard recommendations, clinical
      management is possible, and diagnosis does not imply immediate surgical
      correction.

PMID- 28512735
TI  - Fluorinated Porous Conjugated Polyporphyrins through Direct C-H Arylation
      Polycondensation: Preparation, Porosity, and Use as Heterogeneous Catalysts for
      Baeyer-Villiger Oxidation.
AB  - By considering the high reactivity of fluorinated iron-porphyrin and good
      stability of porphyrin-based porous polymers, fluorinated iron-porphyrin
      conjugated porous polymers (FPOP-3-6) were synthesized through direct C-H
      arylation polymerization. The obtained materials are chemically and thermally
      stable, of which FPOP-3 exhibits the highest Brunauer-Emmett-Teller specific
      surface area (about 840 m2  g-1 ). For functional studies of the obtained
      polymers as heterogeneous catalysts, catalytic transformation of cycloketones
      into lactones by oxygen through Baeyer-Villiger oxidation was used as a model
      reaction. Fluorinated phenyl substituents of the iron-porphyrin not only are
      beneficial to the conversion, but also can stabilize the porphyrin to resist
      catalyst breakdown. The polymer FPOP-3, with high porosity, exhibits the best
      catalytic efficiency and recycling effect. The recovered catalyst also shows good
      catalytic activities after recycling three times with a small loss in yield.

PMID- 28512737
TI  - Mucinous non-neoplastic cyst of the pancreas: is surgical resection avoidable?

PMID- 28512736
TI  - CAGI4 SickKids clinical genomes challenge: A pipeline for identifying pathogenic
      variants.
AB  - Compared with earlier more restricted sequencing technologies, identification of
      rare disease variants using whole-genome sequence has the possibility of finding
      all causative variants, but issues of data quality and an overwhelming level of
      background variants complicate the analysis. The CAGI4 SickKids clinical genome
      challenge provided an opportunity to assess the landscape of variants found in a
      difficult set of 25 unsolved rare disease cases. To address the challenge, we
      developed a three-stage pipeline, first carefully analyzing data quality, then
      classifying high-quality gene-specific variants into seven categories, and
      finally examining each candidate variant for compatibility with the often complex
      phenotypes of these patients for final prioritization. Variants consistent with
      the phenotypes were found in 24 out of the 25 cases, and in a number of these,
      there are prioritized variants in multiple genes. Data quality analysis suggests
      that some of the selected variants are likely incorrect calls, complicating
      interpretation. The data providers followed up on three suggested variants with
      Sanger sequencing, and in one case, a prioritized variant was confirmed as likely
      causative by the referring physician, providing a diagnosis in a previously
      intractable case.

PMID- 28512738
TI  - First-in-Class Composite Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in
      Practice.
AB  - Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor
      (ARNI) inhibits angiotensin II and neprilysin, enhancing circulating vasoactive
      peptides. It is recommended in heart failure with reduced ejection fraction
      (HFrEF) as a result of the PARADIGM-HF trial.1 This review discusses the
      rationale for neprilysin inhibition, data supporting efficacy, and practical tips
      for patient selection and utilization.

PMID- 28512739
TI  - Normal development of spinal axons in early embryo stages and posterior locomotor
      function is independent of GAL-1.
AB  - It was recently described that Galectin-1 (Gal-1) promotes axonal growth after
      spinal cord injury. This effect depends on protein dimerization, since monomeric
      Gal-1 fails to stimulate axonal re-growth. Gal-1 is expressed in vivo at
      concentrations that favor the monomeric species. The aim of the present study is
      to investigate whether endogenous Gal-1 is required for spinal axon development
      and normal locomotor behavior in mice. In order to characterize axonal
      development, we used a novel combination of 3-DISCO technique with 1-photon
      microscopy and epifluorescence microscopy under high power LED illumination,
      followed by serial image section deconvolution and 3-D reconstruction. Cleared
      whole lgals-1-/- embryos were used to analyze the 3-D cytoarchitecture of motor,
      commissural, and sensory axons. This approach allowed us to evaluate axonal
      development, including the number of fibers, fluorescence density of the fiber
      tracts, fiber length as well as the morphology of axonal sprouting, deep within
      the tissue. Gal-1 deficient embryos did not show morphological/anatomical
      alterations in any of the axonal populations and parameters analyzed. In
      addition, specific guidance receptor PlexinA4 did not change its axonal
      localization in the absence of Gal-1. Finally, Gal-1 deficiency did not change
      normal locomotor activity in post-natal animals. Taken together, our results show
      that development of spinal axons as well as the locomotor abilities observed in
      adult mice are independent of Gal-1. Supporting our previous observations, the
      present study further validates the use of lgals-1-/- mice to develop spinal cord
      or traumatic brain injury models for the evaluation of the regenerative action
      of Gal-1.

PMID- 28512740
TI  - Excited-state minima and emission energies of retinal chromophore analogues:
      Performance of CASSCF and CC2 methods as compared with CASPT2.
AB  - This study provides gas-phase S1 excited-state geometries along with emission and
      adiabatic energies for methylated/demethylated and ring-locked analogues of
      protonated Schiff base retinal models comprising system of five conjugated double
      bonds (PSB5), using second order multiconfiguration perturbation theory (CASPT2).
      CASPT2 results serve as reference data to assess the performance of CC2 (second
      order approximate coupled cluster singles and doubles) and a commonly used
      CASSCF/CASPT2 protocol, that is, complete active space self-consistent field
      (CASSCF) geometry optimization followed by CASPT2 energy calculation. We find
      that the CASSCF methodology fails to locate planar S1 minimum energy structures
      for four out of five investigated planar models in contrast to CC2 and CASPT2
      methods. However, for those which were found: one planar and two twisted minima,
      there is an excellent agreement between CASSCF and CASPT2 results in terms of
      geometrical parameters, one-electron properties, as well as emission and
      adiabatic energies. CC2 performs well for in-plane S1 minima and their
      spectroscopic and electronic properties. However, this picture deteriorates for
      twisted minima. As expected, the CC2 description of the S2 electronic state, with
      strong multireference and significant double excitation character, is very poor,
      exhibiting errors in transition energies exceeding 1 eV. They may be
      substantially diminished by recalculating transition energies with CASPT2 method.
      Our work shows that CASSCF/CASPT2 and CC2 shortcomings may influence gas-phase
      retinal analogues' excited state description in a dramatic way. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28512741
TI  - Intervention for elevated intracranial pressure improves success rate after
      repair of spontaneous cerebrospinal fluid leaks.
AB  - OBJECTIVES/HYPOTHESIS: Spontaneous cerebrospinal fluid (CSF) leaks are associated
      with increased intracranial pressure (ICP) and considered a manifestation of
      idiopathic intracranial hypertension. Although postoperative acetazolamide and
      placement of CSF shunt systems are considered valuable interventions for elevated
      ICP, the impact on recurrence rate remains unclear. The objective of this study
      was to systematically review evidence from reported literature to evaluate
      whether postoperative ICP management reduces recurrence rates after primary
      endoscopic repair. STUDY DESIGN: Prospective case series and systematic review.
      METHODS: Demographics, defect location, success rates, and ICP management in
      spontaneous CSF leak patients were prospectively collected over 8 years. A search
      was also conducted in PubMed to identify studies reporting cases of spontaneous
      CSF rhinorrhea. RESULTS: Fifty-six articles with nonduplicated data were
      identified and combined with a prospective series of 108 patients for a total of
      679 patients treated for spontaneous CSF rhinorrhea. Average age was 50.4 years
      with 77% female. Average body mass index was 35.8 kg/m2 . Defects were most
      commonly located in the sphenoid sinus (n = 334) followed by the ethmoid (n =
      318) and the frontal sinus (n = 46). Successful primary repair was 92.82% in
      patient cohorts where ICP evaluation and intervention with acetazolamide or CSF
      shunt systems was performed, but was significantly decreased to 81.87% in series
      with no active management of elevated ICP (P < .001). CONCLUSIONS: Evaluation and
      intervention for elevated ICP in spontaneous CSF leaks is associated with
      significantly improved success rates following primary endoscopic repair. LEVEL
      OF EVIDENCE: 4. Laryngoscope, 127:2011-2016, 2017.

PMID- 28512742
TI  - Differing intrinsic biological properties between forebrain and spinal
      oligodendroglial lineage cells.
AB  - Differentiation of oligodendroglial progenitor cells (OPCs) into myelinating
      oligodendrocytes is known to be regulated by the microenvironment where they
      differentiate. However, current research has not verified whether or not
      oligodendroglial lineage cells (OLCs) derived from different anatomical regions
      of the central nervous system (CNS) respond to microenvironmental cues in the
      same manner. Here, we isolated pure OPCs from rat neonatal forebrain (FB) and
      spinal cord (SC) and compared their phenotypes in the same in vitro conditions.
      We found that although FB and SC OLCs responded differently to the same external
      factors; they were distinct in proliferation response to mitogens,
      oligodendrocyte phenotype after differentiation, and cytotoxic responses to alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type glutamate receptor-mediated
      excitotoxicity at immature stages of differentiation in a cell-intrinsic manner.
      Moreover, transcriptome analysis identified genes differentially expressed
      between these OPC populations, including those encoding transcription factors
      (TFs), cell surface molecules, and signaling molecules. Particularly, FB and SC
      OPCs retained the expression of FB- or SC-specific TFs, such as Foxg1 and Hoxc8,
      respectively, even after serial passaging in vitro. Given the essential role of
      these TFs in the regional identities of CNS cells along the rostrocaudal axis,
      our results suggest that CNS region-specific gene regulation by these TFs may
      cause cell-intrinsic differences in cellular responses between FB and SC OLCs to
      extracellular molecules. Further understanding of the regional differences among
      OPC populations will help to improve treatments for demyelination in different
      CNS regions and to facilitate the development of stem cell-derived OPCs for cell
      transplantation therapies for demyelination. Cover Image for this issue: doi.
      10.1111/jnc.13809.

PMID- 28512743
TI  - Proteinase 3-antineutrophil cytoplasmic antibody-associated cutaneous vasculitis
      without systemic involvement.

PMID- 28512744
TI  - Incremental benefit of three-dimensional transesophageal echocardiography in the
      assessment of left main coronary artery stent protrusion.
AB  - Ostial lesions represent a challenging clinical scenario and percutaneous
      intervention (PCI) of left main coronary artery ostial lesions has been
      associated with postintervention complications, including protrusion of deployed
      stents into a sinus of Valsalva or aortic root. We report a case of stent
      protrusion into the aortic root following aorto-ostial left main coronary artery
      PCI, in which three-dimensional transesophageal echocardiography (3DTEE) provided
      incremental benefit over standard two-dimensional images. Specifically, 3DTEE
      confirmed the presence of stent protrusion by allowing clear visualization of the
      stent scaffold, in addition to characterizing the relationship between the stent
      and surrounding structures.

PMID- 28512745
TI  - Implementation of multidisciplinary care reduces maternal mortality in women with
      sickle cell disease living in low-resource setting.
AB  - Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women
      with SCD living in low-resource settings, pregnancy is associated with
      significantly increased maternal and perinatal mortality rates. We tested the
      hypothesis that implementing a multidisciplinary obstetric and hematology care
      team in a low-resource setting would significantly reduce maternal and perinatal
      mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching
      Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric
      hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The
      pre-intervention period was assessed through a retrospective chart review to
      identify every death and the post-intervention period was assessed prospectively.
      Interventions consisted of joint obstetrician and hematologist outpatient and
      acute inpatient reviews, close maternal and fetal surveillance, and simple
      protocols for management of acute chest syndrome and acute pain episodes. Primary
      outcomes included maternal and perinatal mortality rates before and after the
      study period. A total of 158 and 90 pregnant women with SCD were evaluated in the
      pre- and post- intervention periods, respectively. The maternal mortality rate
      decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100
      000 at post-intervention, representing a risk reduction of 89.1% (P = 0.007).
      Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention
      to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P
      = 0.20). A multidisciplinary obstetric and hematology team approach can
      dramatically reduce maternal and perinatal mortality in a low-resource setting.

PMID- 28512747
TI  - Visuoperceptual processing in children with neurofibromatosis type 1: True
      deficit or artefact?
AB  - Impairments in visuoperceptual processing have long been considered a hallmark
      deficit of individuals with Neurofibromatosis type 1 (NF1). However, it is
      unclear which specific visuoperceptual subprocesses are impaired and whether
      impairments on these tasks really result from visuoperceptual impairments or
      rather from confounding factors like Executive Functioning (EF) impairments,
      lower intelligence (IQ) and/or co-occurring symptoms of Autism Spectrum Disorder
      (ASD). To answer these questions, we administered four visuoperceptual tasks and
      two control tasks in 39 children with NF1, 52 typically developing children and
      52 children with ASD (8-18 years), all matched for age and gender. Furthermore,
      EF, IQ, and symptoms of ASD were assessed. Children with NF1 displayed intact
      visual form discrimination and intact information integration along the dorsal
      visual pathway. Moreover, their reduced performance on a task requiring
      integration of information along the ventral visual stream and their more detail
      oriented processing style appeared to result from confounding EF impairments and
      not from visuoperceptual impairments per se. The co-occurring ASD symptoms and
      lower IQ of the children with NF1 did not impact substantially upon their
      visuoperceptual performance. These findings point to the large impact of EF
      impairments on the performance of visuoperceptual task and suggest that
      individuals with NF1 show intact visual form discrimination, intact visual
      integration, and typical visual processing style when potential confounding
      factors are controlled for. This may have large repercussions for the
      interpretation of other findings on visuoperceptual processing in individuals
      with NF1. (c) 2017 Wiley Periodicals, Inc.

PMID- 28512746
TI  - A panel of microRNAs can be used to determine oral squamous cell carcinoma.
AB  - BACKGROUND: Subjective histopathology is currently used to diagnose oral squamous
      cell carcinoma (OSCC). We tested if abundances of a panel of microRNA could be an
      objective OSCC indicator. METHOD: Literature review enabled identification of 10
      microRNAs associated with oral and head and neck malignancies. We extracted RNA
      from formalin-fixed paraffin-embedded biopsies; 20 each with OSCC, dysplasia, or
      histologically normal epithelium (HNE) and 10 with oral lichen planus (OLP).
      Relative abundances of microRNAs in HNE and OSCC were determined using reverse
      transcription and then real-time PCR with global mean normalization. MicroRNAs
      differentially expressed (test microRNA, T-miR) and non-differentially expressed
      (normalization microRNA, N-miR) were identified. The raw microRNA Cq data were
      incorporated in a developed algorithm that output a T-miR expression value (T
      miREV) score. Raw Cq data from HNE, OSCC, dysplasia, and OLP samples were then
      used to test the algorithm scoring and OSCC classification. RESULTS: Four test
      and normalization microRNAs were identified. Algorithm output of T-mirEV >1 or <
      1 indicated high and low OSCC probability score, respectively, and gave 88.9%
      sensitivity, 100% specificity, and 93.5% accuracy. Grouping high and intermediate
      T-mirEV scores (T-miREV >=-1) resulted in sensitivity of 90%, specificity of 65%,
      and accuracy of 77.5% in OSCC classification. All 20 dysplasias and eight of 10
      OLP had T-miREV >=-1 indicating intermediate to high probability of malignant
      changes. CONCLUSION: A microRNA panel combined with our algorithm can identify
      tissue with probable oncogenic changes. IMPACT: The developed algorithm serves as
      a baseline for prospective trials, which may result in potential clinical
      utility.

PMID- 28512749
TI  - Anxiety genetics: Dispatches from the frontier.

PMID- 28512750
TI  - Genetic risk variants for social anxiety.

PMID- 28512748
TI  - Genetic influences on ADHD symptom dimensions: Examination of a priori
      candidates, gene-based tests, genome-wide variation, and SNP heritability.
AB  - Although the heritability of ADHD is estimated to be high, identifying specific
      genetic markers remains challenging. Most studies to date have examined the
      genetic basis of ADHD by employing dichotomous diagnostic phenotypes, but, as
      ADHD symptoms tend to be phenotypically dimensional, an alternative and
      potentially informative approach is to examine continuous indices of inattention
      and hyperactivity-impulsivity symptoms. The current study aimed to identify
      genetic effects on dimensionally-focused adult ADHD-related phenotypes in 990
      individuals of European ancestry with intentionally low levels of substance
      misuse to avoid confounding. The study used four complementary approaches: (1)
      analysis of a priori candidate loci identified in prior meta-analytic work; (2)
      gene-based analysis; (3) hypothesis-free genome-wide association testing; and (4)
      single nucleotide polymorphism (SNP) heritability via genomic-relatedness-matrix
      restricted maximum likelihood analysis (GREML). The GREML analysis included a
      bivariate model to test whether the ADHD symptom dimensions index the same
      genetic liability. The results revealed significant differential associations
      between two a priori loci and ADHD phenotypes, rs6296 in HTR1B with inattention
      and rs3746544 in SNAP-25 with hyperactivity-impulsivity. No significant gene
      based or genome-wide associations were detected, but SNP heritability revealed
      that a large portion of genetic variance was accounted for by common SNPs (44%,
      55%, and 59% for inattention, hyperactivity-impulsivity, and total ADHD,
      respectively) and substantial shared genetic variance across inattention and
      hyperactivity-impulsivity (86%). These findings reveal both unique and common
      patterns of genetic influences across dimensional ADHD-related phenotypes. More
      broadly, these findings reveal the value in using multiple methods to understand
      the genetic etiology of ADHD.

PMID- 28512751
TI  - Giant torturous left circumflex artery draining to the right atrium.
AB  - Coronary artery anomalies represent a diverse group of congenital disorders
      characterized by abnormalities of coronary arteries anatomy. We describe an
      extremely rare case of giant torturous left circumflex artery draining to the
      right atrium manifesting by palpitations and atrial fibrillation.

PMID- 28512752
TI  - An Optimized Two-Photon Fluorescent Probe for Biological Sensing and Imaging of
      Catechol-O-Methyltransferase.
AB  - A practical two-photon fluorescent probe was developed for highly sensitive and
      selective sensing of the activities of catechol-O-methyltransferase (COMT) in
      complex biological samples. To this end, a series of 3-substituted 7,8
      dihydroxycoumarins were designed and synthesized. Among them, 3-BTD displayed the
      best combination of selectivity, sensitivity, reactivity, and fluorescence
      response following COMT-catalyzed 8-O-methylation. The newly developed two-photon
      fluorescent probe 3-BTD can be used for determining the activities of COMT in
      complex biological samples and bio-imaging of endogenous COMT in living cells and
      tissue slices with good cell permeability, low cytotoxicity, and high imaging
      resolution. All these findings suggest that 3-BTD holds great promise for
      developing therapeutic molecules that target COMT, as well as for exploring COMT
      associated biological processes and its biological functions in living systems.
      Furthermore, the strategy also sheds new light on the development of fluorescent
      probes for other conjugative enzymes.

PMID- 28512754
TI  - An unusual case of methicillin-resistant Staphylococcus aureus necrotic soft
      tissue infection of the lip.

PMID- 28512755
TI  - Evaluation of safety of concomitant splenectomy in living donor liver
      transplantation: a retrospective study.
AB  - In Asian countries, concomitant splenectomy in living donor liver transplantation
      (LDLT) is indicated to modulate the portal vein pressure in the small-sized graft
      to protect against small for size syndrome. While concomitant splenectomy in
      deceased donor liver transplantation is almost contraindicated based on Western
      Reports of increased mortality and morbidity rate due to septic complications,
      there are few studies about that in LDLT. So, we retrospectively investigated the
      clinical outcome of adult LDLT at Kyoto University Hospital from July 2010 to
      July 2016. We divided the patients (n = 164) into those with concomitant
      splenectomy (n = 88) and those without (n = 76). The splenectomy group showed
      significantly increased operative time and intraoperative blood loss (P = 0.008,
      P = 0.0007, respectively), and significantly higher rate of postoperative splenic
      vein thrombosis and cytomegalovirus infection (P = 0.03, P = 0.016,
      respectively). However, there were no significant differences between the two
      groups regarding the incidence of postoperative hemorrhage (P = 0.06), post
      transplant bacteremia (P = 0.38), infection-related mortality rates (P = 0.8),
      acute rejection (P = 0.87), and patient and graft survival (P = 0.66, P = 0.67
      respectively); finally, model for end-stage liver disease score above 30 was an
      independent predictor for infection-related mortality post-transplant (HR = 5.99,
      95% CI = 2.15-16.67, P = 0.001). In conclusion, concomitant splenectomy in LDLT
      can be safely performed when indicated.

PMID- 28512753
TI  - Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis.
AB  - OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are
      shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations
      in peripheral blood. Various diseases causing neuronal damage have resulted in
      elevated CSF concentrations. We explored the value of an ultrasensitive single
      molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).
      METHODS: sNfL levels were measured in healthy controls (HC, n = 254) and two
      independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n
      = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow
      up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation
      to concurrent clinical, imaging, and treatment parameters and to future clinical
      outcomes. RESULTS: sNfL levels were higher in both MS cohorts than in HC (p <
      0.001). We found a strong association between CSF NfL and sNfL (beta = 0.589, p <
      0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both
      brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had
      higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; beta = 1.461, p =
      0.005 and beta = 1.902, p = 0.002, respectively). sNfL was independently
      associated with Expanded Disability Status Scale (EDSS) assessments (beta =
      1.105, p < 0.001) and presence of relapses (beta = 1.430, p < 0.001). sNfL levels
      were lower under disease-modifying treatment (beta = 0.818, p = 0.003). Patients
      with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based
      percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio
      = 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening
      (97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034). INTERPRETATION:
      These results support the value of sNfL as a sensitive and clinically meaningful
      blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann
      Neurol 2017;81:857-870.

PMID- 28512756
TI  - Nitramino- and Dinitromethyl-Substituted 1,2,4-Triazole Derivatives as High
      Performance Energetic Materials.
AB  - Since highly nitrated nitrogen-rich heterocycles are important motifs in high
      energy density materials, extensive studies for the development of such novel
      molecules have been underway. A highly energetic moiety, 3-dinitromethyl-5
      nitramino-1,2,4-triazole, which consists of a triazole ring, and nitramino and
      dinitromethyl groups, has been designed and synthesized. By pairing with nitrogen
      rich cations, several ionic derivatives were obtained. Theoretical and
      experimental studies show that the hydroxylammonium salt (7) is highly dense, and
      has excellent detonation performance with acceptable thermal stablity and
      sensitivities, which are superior to those of RDX.

PMID- 28512757
TI  - Sense of coherence and oral health in older adults in Southern Brazil.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between sense of
      coherence and oral health among older adults treated at family health units in
      southern Brazil. MATERIAL AND METHODS: The sample was composed of 164 individuals
      aged 60 years old or older. Socio-demographic and oral health variables were
      collected using a standardised questionnaire. Sense of coherence (SOC) was
      measured with the questionnaire proposed by Antonovsky containing 29 closed-ended
      questions. Poisson regression analysis was employed to identify factors
      associated with SOC. RESULTS: Among the 164 older adults, 53.9% were edentate,
      54.5% did not need any type of dental prosthesis, and 82.1% had good/adequate
      self-assessed oral health. The multivariate analysis revealed lower SOC scores
      among non-white individuals [Mean Ratio (MR)=0.94; 95% CI: 0.91-0.97; P<.001],
      with poor/very poor self-assessed oral health (MR=0.85; 95% CI: 0.78-0.91;
      P<.001) and with one or more teeth present in the oral cavity (MR=0.94; 95% CI:
      0.91-0.97; P<.001). CONCLUSION: The present results show that older adults who
      are self-reported as non-white, with one or more teeth in the oral cavity and
      with poor/very poor self-assessed oral health have lower SOC scores.

PMID- 28512758
TI  - Reporting practices for unsolicited and secondary findings from next-generation
      sequencing technologies: Perspectives of laboratory personnel.
AB  - While next-generation sequencing (NGS) has enormous potential to identify genetic
      causes of disease, the nature of the technology means that it can also identify
      additional information about the individual receiving sequencing that is
      unrelated to the original rationale for testing. Reporting these unsolicited
      findings (UF) to clinicians, and subsequently to patients, could lead to
      potentially lifesaving interventions. Most international guidelines provide
      limited specific recommendations as to whether these UF should be reported.
      Little research has been conducted exploring which of these variants are reported
      in practice. Twenty-six interviews were conducted with 27 laboratory personnel,
      representing 24 laboratories in Europe (12), Canada (five), and Australasia
      (Seven) to explore their reporting practices. There is considerable variation
      between laboratories in the reporting of UF. While some limit their reporting to
      findings that are relevant to the clinical question, others report UF to varying
      degrees. In addition, most laboratory personnel interviewed said that their
      laboratories do not actively search for secondary findings in disease-causing
      genes unrelated to the clinical question, such as those suggested by the American
      College of Medical Genetics and Genomics. Our study highlights that laboratories
      are still grappling with decisions about which UF to report from NGS and are
      calling for more guidance.

PMID- 28512759
TI  - Effect of pH on rheotaxis of bull sperm using microfluidics.
AB  - The aim of the present research is to study the effect of pH values on the sperm
      rheotaxis properties. Semen collected from bulls was diluted with SOF medium
      (1:10). pH of the medium was adjusted using a digital pH meter to the following
      pH values: 6.0, 6.2, 6.4, 6.4, 6.8, 7.0. All kinetic parameters of sperm (n =
      3,385) were determined through a computer-assisted sperm analysis (CASA) system
      using microfluidic devices with controlled flow velocity. The following
      parameters were determined: total motility (TM%), positive rheotaxis (PR%),
      straightline velocity (VSL, MUm/s), average path velocity (VAP, MUm/s), linearity
      (LIN, as VSL/VCL, %), beat cross-frequency (BCF, Hz) and curvilinear velocity
      (VCL, MUm/s). Nitric oxide, calcium and potassium were estimated in semen at
      different pH values. To confirm the effect of nitric oxide and K+ , we used
      sodium nitroprusside (an NO donor) and KCL as (a K+ donor) to see their effect on
      sperm PR%. The results showed no difference in TM% at pH (6-7). The PR% was the
      lowest at pH 6 and 7. The best parameters for the PR% were at pH 6.4-6.6. The
      concentration of Ca+2 did not change at different pH values. The mean NO values
      decreased with the increase of pH; however, the mean values of K+ increased with
      the increase of pH. Addition of high concentration of NO and K+ to the semen
      media at fixed pH level had a negative effect on TM% and PR%. In conclusion, the
      bull sperm had the best rheotaxis properties at pH 6.4-6.6 and sensitive to the
      change of seminal NO and K+ .

PMID- 28512760
TI  - Different perspectives of validity in psychiatry.
AB  - It is important to improve our understanding about what might be the specific
      characteristics of mental disorders to strengthen the scientific credibility of
      psychiatry and to clarify its position among other medical and nonmedical
      sciences. On the other hand, this issue has diagnostic, research, therapeutic,
      legal, financial, and moral implications. Some authors defend a realistic and
      absolutist attitude towards validity and others an instrumental and relativistic
      stance. Regarding the organization of concepts, dimensional or categorical
      approaches have both advantages and disadvantages. Regarding the methodology by
      which validity is sought, it can be oriented externally or internally to the
      concept in question. On the other hand, the validity can be expert driven or data
      driven, the research can be based on disorders or in symptoms and quantitative or
      qualitative methods may be used. In this article, we review all these different
      kinds of perspectives that can be taken towards the definition of validity in
      psychiatry and the methodology to search for it.

PMID- 28512762
TI  - Importance of Group Therapeutic Support for Family Members of Children with
      Alopecia Areata: A Cross-Sectional Survey Study.
AB  - BACKGROUND/OBJECTIVES: The psychological effect of alopecia areata (AA) is well
      documented, but group interaction may help lessen this burden. We aimed to
      determine factors that draw patients with AA and their families to group events.
      METHODS: Surveys were administered at the annual alopecia areata bowling social
      in 2015 and 2016. This event is a unique opportunity for children with AA and
      their families to meet others with the disease and connect with local support
      group resources from the Minnesota branch of the National Alopecia Areata
      Foundation. Data from 2015 and 2016 were combined. Comparisons of subgroups were
      performed using Fisher exact tests for response frequencies and percentages and
      two-sample t tests for mean values. RESULTS: An equal number of men and women
      participated in the study (n = 13 each). The average age was 41.1 years. There
      were no significant differences (p > 0.05) in survey responses based on
      respondent age or sex. Twenty-three (88.5%) attendees sought to connect with
      others with AA and met three or more people during the event. Seventeen (65.4%)
      also attended other support group events. Twelve respondents (46.2%) came to
      support a friend or family member. One hundred percent of attendees identified
      socializing with others with AA as important. CONCLUSIONS: Group interaction is
      an important source of therapeutic support for people with AA and their families.

PMID- 28512764
TI  - Maternal fructose consumption can affect offspring metabolic outcomes.

PMID- 28512761
TI  - Deconstructing white matter connectivity of human amygdala nuclei with thalamus
      and cortex subdivisions in vivo.
AB  - Structural alterations in long-range amygdala connections are proposed to
      crucially underlie several neuropsychiatric disorders. While progress has been
      made in elucidating the function of these connections, our understanding of their
      structure in humans remains sparse and non-systematic. Harnessing diffusion
      weighted imaging and probabilistic tractography in humans, we investigate
      connections between two main amygdala nucleus groups, thalamic nuclei, and
      cortex. We first parcellated amygdala into deep (basolateral) and superficial
      (centrocortical) nucleus groups, and thalamus into six subregions, using
      previously established protocols based on connectivity. Cortex was parcellated
      based on T1-weighted images. We found substantial amygdala connections to
      thalamus, with different patterns for the two amygdala nuclei. Crucially, we
      describe direct subcortical connections between amygdala and paraventricular
      thalamus. Different from rodents but similar to non-human primates, these are
      more pronounced for basolateral than centrocortical amygdala. Substantial white
      matter connectivity between amygdala and visual pulvinar is also more pronounced
      for basolateral amygdala. Furthermore, we establish detailed connectivity
      profiles for basolateral and centrocortical amygdala to cortical regions. These
      exhibit cascadic connections with sensory cortices as suggested previously based
      on tracer methods in non-human animals. We propose that the quantitative
      connectivity profiles provided here may guide future work on normal and
      pathological function of human amygdala. Hum Brain Mapp 38:3927-3940, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28512765
TI  - Tail gut cyst: an unusual case.

PMID- 28512763
TI  - Impact of MLH1 expression on tumor evolution after curative surgical tumor
      resection in a murine orthotopic xenograft model for human MSI colon cancer.
AB  - Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often
      result from MLH1 deficiency. The aim of this study was to assess the impact of
      MLH1 expression per se on tumor evolution after curative surgical resection using
      a xenograft tumor model. Transplantable tumors established with the human MLH1
      deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were
      implanted onto the caecum of NOD/SCID mice. Curative surgical resection was
      performed at day 10 in half of the animals. The HCT116-derived tumors were more
      voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and
      peritoneal carcinomatosis occurred significantly more often in the group of mice
      grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice
      did not develop peritoneal carcinomatosis or liver metastasis. After surgical
      resection, lymph node metastases only arose in the group of mice implanted with
      HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P =
      .047). The murine orthotopic xenograft model based on isogenic human CRC cell
      lines allowed us to reveal the impact of MLH1 expression on tumor evolution in
      mice who underwent curative surgical resection and in mice whose tumor was left
      in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only
      governed by mutations arising in genes harboring microsatellite repeated
      sequences but also from their defect in MLH1 as such.

PMID- 28512768
TI  - Nursing home prices and quality of care - Evidence from administrative data.
AB  - There is widespread concern about the quality of care in nursing homes. On the
      basis of administrative data of a large health insurance fund, we investigate
      whether nursing home prices are associated with relevant quality of care
      indicators at the resident level. Our results indicate negative associations
      between price and both inappropriate and psychotropic medication. In contrast, we
      do not find any relationship between the price and impairments of physical
      health.

PMID- 28512766
TI  - Mental health outcomes of developmental coordination disorder in late
      adolescence.
AB  - AIM: To assess the relationship between developmental coordination disorder (DCD)
      and mental health outcomes in late adolescence. METHOD: Data were analyzed from
      the Avon Longitudinal Study of Parents and Children. Moderate-to-severe DCD was
      defined at 7 to 8 years according to the DSM-IV-TR criteria. Mental health was
      assessed at 16 to 18 years using self-reported questionnaires: Strengths and
      Difficulties Questionnaire, Short Moods and Feelings Questionnaire, and the
      Warwick-Edinburgh Mental Well-being Scale. Logistic and linear regressions
      assessed the associations between DCD and mental health, using multiple
      imputation to account for missing data. Adjustments were made for socio-economic
      status, IQ, and social communication difficulties. RESULTS: Adolescents with DCD
      (n=168) had an increased risk of mental health difficulties (total Strengths and
      Difficulties Questionnaire score) than their peers (n=3750) (odds ratio 1.78, 95%
      confidence interval 1.12-2.83, adjusted for socio-economic status and IQ). This
      was, in part, mediated through poor social communication skills. Adolescent
      females with DCD (n=59) were more prone to mental health difficulties than males.
      Greater mental well-being was associated with better self-esteem (beta 0.82,
      p<0.001). INTERPRETATION: Individuals with DCD, particularly females, had
      increased risk of mental health difficulties in late adolescence. Interventions
      that aim to promote resilience in DCD should involve improving social
      communication skills and self-esteem.

PMID- 28512767
TI  - Duration of major and minor depressive episodes and associated risk indicators in
      a psychiatric epidemiological cohort study of the general population.
AB  - OBJECTIVE: Hardly any studies exist on the duration of major depressive disorder
      (MDD) and factors that explain variations in episode duration that lack biases.
      This limits clinical decision-making and leaves patients wondering when they will
      recover. METHOD: Data were used from the Netherlands Mental Health Survey and
      Incidence Study-2, a psychiatric epidemiological cohort study among a nationally
      representative adult population. Respondents with a newly originated depressive
      episode were selected: 286 MDD and 107 minor depressive disorder (MinDD) cases.
      DSM-IV diagnoses were assessed with the Composite International Diagnostic
      Interview 3.0 and episode duration with the Life Chart Interview. RESULTS: Among
      MDD cases, median episode duration was 6 months, mean duration was 10.7 months,
      and 12% had not recovered at 36 months. Longer duration was associated with
      comorbid dysthymia, anxiety disorder, psychotropic medication use (i.e.
      antidepressants or benzodiazepines prescribed by a mental health professional),
      mental health care use and suicidal behaviour. Better physical and mental
      functioning before depression onset predicted shorter duration. Among MinDD
      cases, shorter median duration (3 months) but similar mean duration (8.7 months),
      risk of chronicity (10% not recovered at 36 months) and risk indicators for
      episode duration were found. CONCLUSION: As the risk of chronicity was similar
      for MDD and MinDD, MinDD cannot be dismissed as a merely brief mood state.

PMID- 28512769
TI  - Modern cardiac surgery: the future of cardiac surgery in Australia.
AB  - Cardiac surgery is a relatively young specialty and is undergoing many changes
      presently. The advent of catheter-based technology, minimally invasive surgery
      and better information regarding the roles of cardiac surgery in the management
      of common cardiac disease is changing the way we provide services. In Australia,
      attention must be turned to the way cardiac surgical services are provided to
      enable delivery of modern procedures. This has implications for the provision of
      training. We explore the face of modern cardiac surgery and how this may be taken
      up in Australia.

PMID- 28512770
TI  - Role of Halide Ions in the Nature of the Magnetic Anisotropy in Tetrahedral CoII
      Complexes.
AB  - A series of mononuclear tetrahedral CoII complexes with a general molecular
      formula [CoL2 X2 ] [L=thiourea and X=Cl (1), Br (2) and I (3)] were synthesized
      and their structures were characterized by single-crystal X-ray diffraction.
      Direct-current (dc) magnetic susceptibility [chiM T(T) and M(H)] and its slow
      relaxation of magnetization were measured for all three complexes. The
      experimental dc magnetic data are excellently reproduced by fitting both chiM
      T(T) and M(H) simultaneously with the parameters D=+10.8 cm-1 , g1 =2.2, g2 =2.2,
      and g3 =2.4 for 1; D=-18.7 cm-1 , giso =2.21 for 2; and D=-19.3 cm-1 , giso =2.3
      for 3. The replacement of chloride in 1 by bromide or iodide (in 2 and 3,
      respectively) was accompanied by a change in both sign and magnitude of the
      magnetic anisotropy D. Field-induced out-of-phase susceptibility signals observed
      in 10 % diluted samples of 1-3 imply slow relaxation of magnetization of
      molecular origin. To better understand the magnetization relaxation dynamics of
      complexes 1-3, detailed ab initio CASSCF/NEVPT2 calculations were performed. The
      computed spin Hamiltonian parameters are in good agreement with experimental
      data. In particular, the calculations unveil the role of halide ions in switching
      the sign of D on moving from Cl- to I- . The large spin-orbit coupling constant
      associated with the heavier halide ion and weaker pi donation reduces the ground
      state-excited state gap, which leads to a larger contribution to negative D for
      complex 3 compared to complex 1. Further magnetostructural D correlations were
      developed to understand the role of structural distortion in the sign and
      magnitude of D values in this family of complexes.

PMID- 28512771
TI  - Negative Cardiovascular Consequences of Small Molecule Immunosuppressants.
AB  - Immunosuppressants are critical after transplantation and prescribed as immune
      modulators for autoimmune disorders and glomerulonephritides. Immunosuppressants
      include large (e.g., thymoglobulin, alemtuzumab, and rituximab) and small
      molecules (e.g., corticosteroids, calcineurin inhibitors, antimetabolites, and
      mammalian target of rapamycin (mTOR) inhibitors). The majority of the small
      molecules worsen traditional cardiovascular risks. This review describes
      cardiovascular risks of small molecule immunosuppressants: corticosteroids,
      calcineurin inhibitors (tacrolimus and cyclosporine), and mTOR inhibitors
      (rapamycin), by categorizing these risks into two categories: ischemic heart
      disease and nonischemic cardiac effects.

PMID- 28512772
TI  - Subspecialty approach for the management of acute cholecystitis: an alternative
      to acute surgical unit model of care.
AB  - BACKGROUND: Acute cholecystitis is a common condition. Recent studies have shown
      an association between creation of an acute surgical unit (ASU) and improved
      outcomes. This study aimed to evaluate the outcomes of a subspecialty based
      approach to the management of acute cholecystitis as an alternative to the
      traditional 'generalist' general surgery approach or the ASU model. METHOD: A 6
      year retrospective analysis of outcomes in patients admitted under a dedicated
      upper gastrointestinal service for acute cholecystitis undergoing emergency
      laparoscopic cholecystectomy. RESULTS: Seven hundred emergency laparoscopic
      cholecystectomies were performed over this time. A total of 486 patients were
      available for analysis. The median time to operation was 2 days and median length
      of operation was 80 min. A total of 86.9% were performed during daylight hours.
      Eight cases were converted to open surgery (1.6%). Intra-operative
      cholangiography was performed in 408 patients. The major complication rate was
      8.2%, including retained common bile duct stones (2.3%), sepsis (0.2%), post
      operative bleeding (0.4%), readmission (0.6%), bile leak (2.1%), AMI (0.4%),
      unscheduled return to theatre (0.6%) and pneumonia (0.8%). There were no
      mortalities and no common bile duct injuries. CONCLUSION: Over a time period that
      encompasses the current publications on the ASU model, a subspecialty model of
      care has shown consistent results that exceed established benchmarks.
      Subspecialty management of complex elective pathologies has become the norm in
      general surgery and this study generates the hypothesis that subspecialty
      management of patients with complex emergency pathologies should be considered a
      valid alternative to ASU. Access block to emergency theatres delays treatment and
      prolongs hospital stay.

PMID- 28512773
TI  - Natural history of intraductal papillary mucinous neoplasm and non-neoplastic
      cyst: long-term imaging follow-up study.
AB  - BACKGROUND: To identify differences in incidence and mortality of pancreatic
      cancer (PC) between intraductal papillary mucinous neoplasm (IPMN) and non
      neoplastic cyst. METHODS: Patients with pancreatic cyst (n = 526; 263 with IPMN
      and 263 with non-neoplastic cyst matched for age, sex, and diagnosis year) were
      periodically followed-up with imaging. Hazard ratio (HR), standardized incidence
      ratio (SIR), and standardized mortality ratio (SMR) for PC and PC-related
      mortality were estimated. RESULTS: During a mean follow-up of 57.5 months with
      3,376 computed tomography scans and 1,079 magnetic resonance imaging scans, 5
      year cumulative PC incidence was 4.0% for IPMN and 0% for non-neoplastic cyst,
      respectively (HR 5.2; P = 0.031). During a mean follow-up of 73.1 months, 5-year
      cumulative PC-related mortality was 2.6% for IPMN and 0% for non-neoplastic cyst,
      respectively (HR 4.5; P = 0.05). Compared with the general population in Japan,
      patients with IPMN, but not those with non-neoplastic cyst, had significantly
      increased risks of PC incidence (SIR 22.03) and related mortality (SMR 15.9).
      CONCLUSIONS: During long-term imaging follow-up, patients with IPMN developed PC
      over time, whereas none of the patients with non-neoplastic cyst developed it
      within 5 years. Compared with the general population, patients with IPMN, but not
      those with non-neoplastic cyst, were at risk of PC and related mortality.

PMID- 28512774
TI  - Cybersecurity and medical devices: A practical guide for cardiac
      electrophysiologists.
AB  - Medical devices increasingly depend on software. While this expands the ability
      of devices to perform key therapeutic and diagnostic functions, reliance on
      software inevitably causes exposure to hazards of security vulnerabilities. This
      article uses a recent high-profile case example to outline a proactive approach
      to security awareness that incorporates a scientific, risk-based analysis of
      security concerns that supports ongoing discussions with patients about their
      medical devices.

PMID- 28512776
TI  - Can telomere length be used as a biomarker for cardiovascular diseases? Insights
      from a large clinical study.

PMID- 28512775
TI  - A porphyrin-based fluorescence method for zinc determination in commercial
      propolis extracts without sample pretreatment.
AB  - The quantification of zinc in over-the-counter drugs as commercial propolis
      extracts by molecular fluorescence technique using meso-tetrakis(4
      carboxyphenyl)porphyrin (H2 TCPP4 ) was developed for the first time. The
      calibration curve is linear from 6.60 to 100 nmol L-1 of Zn2+ . The detection and
      quantification limits were 6.22 nmol L-1 and 19.0 nmol L-1 , respectively. The
      reproducibility and repeatability calculated as the percentage variation of
      slopes of seven calibration curves were 6.75% and 4.61%, respectively. Commercial
      propolis extract samples from four Brazilian states were analyzed and the results
      (0.329-0.797 mg/100 mL) obtained with this method are in good agreement with that
      obtained with the Atomic Absorption Spectroscopy (AAS) technique. The method is
      simple, fast, of low cost and allows the analysis of the samples without
      pretreatment. Moreover the major advantage is that Zn-porphyrin complex presents
      fluorescent characteristic promoting the selectivity and sensitivity of the
      method.

PMID- 28512777
TI  - The Australian laparoscopic radical prostatectomy learning curve.
AB  - BACKGROUND: International estimates of the laparoscopic radical prostatectomy
      (LRP) learning curve extend to as many as 1000 cases, but is unknown for
      Fellowship-trained Australian surgeons. METHODS: Prospectively collected data
      from nine Australian surgeons who performed 2943 consecutive LRP cases was
      retrospectively reviewed. Their combined initial 100 cases (F100, n = 900) were
      compared to their second 100 cases (S100, n = 782) with two of nine surgeons
      completing fewer than 200 cases. RESULTS: The mean age (61.1 versus 61.1 years)
      and prostate specific antigen (7.4 versus 7.8 ng/mL) were similar between F100
      and S100. D'Amico's high-, intermediate- and low-risk cases were 15, 59 and 26%
      for the F100 versus 20, 59 and 21% for the S100, respectively. Blood transfusions
      (2.4 versus 0.8%), mean blood loss (413 versus 378 mL), mean operating time (193
      versus 163 min) and length of stay (2.7 versus 2.4 days) were all lower in the
      S100. Histopathology was organ confined (pT2) in 76% of F100 and 71% of S100.
      Positive surgical margin (PSM) rate was 18.4% in F100 versus 17.5% in the S100 (P
      = 0.62). F100 and S100 PSM rates by pathological stage were similar with pT2 PSM
      12.2 versus 9.5% (P = 0.13), pT3a PSM 34.8 versus 40.5% (P = 0.29) and pT3b PSM
      52.9 versus 36.4% (P = 0.14). CONCLUSION: There was no significant improvement in
      PSM rate between F100 and S100 cases. Perioperative outcomes were acceptable in
      F100 and further improved with experience in S100. Mentoring can minimize the LRP
      learning curve, and it remains a valid minimally invasive surgical treatment for
      prostate cancer in Australia even in early practice.

PMID- 28512778
TI  - CAGI4 Crohn's exome challenge: Marker SNP versus exome variant models for
      assigning risk of Crohn disease.
AB  - Understanding the basis of complex trait disease is a fundamental problem in
      human genetics. The CAGI Crohn's Exome challenges are providing insight into the
      adequacy of current disease models by requiring participants to identify which of
      a set of individuals has been diagnosed with the disease, given exome data. For
      the CAGI4 round, we developed a method that used the genotypes from exome
      sequencing data only to impute the status of genome wide association studies
      marker SNPs. We then used the imputed genotypes as input to several machine
      learning methods that had been trained to predict disease status from marker SNP
      information. We achieved the best performance using Naive Bayes and with a
      consensus machine learning method, obtaining an area under the curve of 0.72,
      larger than other methods used in CAGI4. We also developed a model that
      incorporated the contribution from rare missense variants in the exome data, but
      this performed less well. Future progress is expected to come from the use of
      whole genome data rather than exomes.

PMID- 28512780
TI  - Novel enantioselective fluorescent sensors for tartrate anion based on
      acridinezswsxa.
AB  - Novel chiral fluorescence sensors L-1 and D-1 incorporating N-Boc-protected
      alanine and acridine moieties were synthesized. The recognition ability of the
      sensors was studied by fluorescence titration, 1 H NMR spectroscopy and density
      functional theory (DFT) calculations. The sensors exhibited good enantioselective
      fluorescent sensing ability toward enantiomers of tartrate anion for the selected
      carboxylate anions and formed 1: 1 complexes by multiple hydrogen bonding
      interactions.

PMID- 28512782
TI  - Aortocoronary artery dissection: a partial aortic root remodelling, aortic valve
      repair and coronary artery bypass.

PMID- 28512779
TI  - Structure of protein emulsion in food impacts intestinal microbiota, caecal
      luminal content composition and distal intestine characteristics in rats.
AB  - SCOPE: Few studies have evaluated in vivo the impact of food structure on
      digestion, absorption of nutrients and on microbiota composition and metabolism.
      In this study we evaluated in rat the impact of two structures of protein
      emulsion in food on gut microbiota, luminal content composition, and intestinal
      characteristics. METHODS AND RESULTS: Rats received for 3 weeks two diets of
      identical composition but based on lipid-protein matrices of liquid fine (LFE) or
      gelled coarse (GCE) emulsion. LFE diet led to higher abundance, when compared to
      the GCE, of Lactobacillaceae (Lactobacillus reuteri) in the ileum, higher beta
      diversity of the caecum mucus-associated bacteria. In contrast, the LFE diet led
      to a decrease in Akkermansia municiphila in the caecum. This coincided with
      heavier caecum content and higher amount of isovalerate in the LFE group. LFE
      diet induced an increased expression of (i) amino acid transporters in the ileum
      (ii) glucagon in the caecum, together with an elevated level of GLP-1 in portal
      plasma. However, these intestinal effects were not associated with modification
      of food intake or body weight gain. CONCLUSION: Overall, the structure of protein
      emulsion in food affects the expression of amino acid transporters and gut
      peptides concomitantly with modification of the gut microbiota composition and
      activity. Our data suggest that these effects of the emulsion structure are the
      result of a modification of protein digestion properties.

PMID- 28512781
TI  - Developmental regulation and localization of carnitine palmitoyltransferases
      (CPTs) in rat brain.
AB  - While the brain's high energy demands are largely met by glucose, brain is also
      equipped with the ability to oxidize fatty acids for energy and metabolism. The
      brain expresses the carnitine palmitoyltransferases (CPTs) that mediate carnitine
      dependent entry of long-chain acyl-CoAs into the mitochondrial matrix for beta
      oxidation - CPT1a and CPT2 located on the outer and inner mitochondrial
      membranes, respectively. Their developmental profile, regional distribution and
      activity as well as cell type expression remain unknown. We determined that brain
      CPT1a RNA and total protein expression were unchanged throughout post-natal
      development (PND0, PND7, PND14, PND21 and PND50); however, CPT2 RNA peaked at PND
      21 and remained unchanged through PND50 in all regions studied (cortex,
      hippocampus, midbrain, and cerebellum). Both long-chain acyl CoA dehydrogenase
      and medium acyl-CoA dehydrogenase showed a similar developmental profile to CPT2.
      Acylcarnitines, generated as a result of CPT1a activity, significantly increased
      with age and peaked at PND21 in all brain regions, concurrent with the increased
      expression of enzymes involved in mitochondrial beta-oxidation. The CPT system is
      highly enriched in vivo in hippocampus and cerebellum, relative to cortex and
      midbrain, and is exclusively present in astrocytes and neural progenitor cells,
      while absent in neurons, microglia, and oligodendrocytes. Using radiolabeled
      oleate, we demonstrate regional differences in brain fatty acid oxidation that
      may be blocked by the irreversible CPT1a inhibitor etomoxir. This study
      contributes to the field of knowledge in brain cell-specific metabolic pathways,
      which are important for understanding normal brain development and aging, as well
      as pathophysiology of neurological diseases. Read the Editorial Comment for this
      article on page 347.

PMID- 28512783
TI  - Effect of silver-loaded PMMA on Streptococcus mutans in a drip flow reactor.
AB  - Orthodontic retention has been proposed as a life-long commitment for patients
      who desire to maintain straight teeth. However, the presence of foreign material
      increases risk of bacterial colonization and caries formation, of which
      Streptococcus mutans is a key contributor. Multiple studies have assessed the
      ability of silver to be added to base plate material and resist attachment of S.
      mutans. However, it does not appear that long-term washout in connection with
      biofilm growth under physiologically relevant conditions has been taken into
      consideration. In this study, silver was added to base plate material and exposed
      to short- or long-term washout periods. Materials were then assessed for their
      ability to resist biofilm formation of S. mutans using a drip flow reactor that
      modeled the human oral environment. Data indicated that silver was able to resist
      biofilm formation following short-term washout, but long-term washout periods
      resulted in a lack of ability to resist biofilm formation. These data will be
      important for future development of base plate materials to achieve long-term
      antimicrobial efficacy to reduce risk of caries formation and benefit patients in
      the long term. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A:
      2632-2639, 2017.

PMID- 28512784
TI  - Evaluation of aromatic radiobromination by nucleophilic substitution using
      diaryliodonium salt precursors.
AB  - Radiobromine-labeled compounds can be used for positron emission tomography (PET)
      imaging (ie, 76 Br) and for radiation therapy (ie, 77 Br). However, the commonly
      used electrophilic substitution reaction using no-carrier-added radiobromide does
      not always afford the desired product due to the high reactivity of the
      brominating intermediate. A nucleophilic substitution by bromide, such as
      radiobromination of iodonium precursors, provides an alternative route for the
      synthesis of bromo-radiopharmaceuticals. The applicability of aromatic
      radiobromination by nucleophilic substitution using diaryliodonium salt
      precursors was evaluated using iodonium model compounds and [76 Br]/[77
      Br]bromide. Radiobromination was observed under all conditions tested, in up to
      quantitative yields. A QMA cartridge treatment method and a base-free method have
      been developed, and no extra base is needed for either methods. The base-free
      conditions are mild and afford much cleaner reactions. Up to 20% water is
      tolerated in the reactions without reducing the radiochemical yields. No-carrier
      added and carrier-added reactions afforded similar results. 4-Bromobenzaldehyde
      and 4-bromobenzoate have been radiosynthesized reliably and in good yields. These
      results indicate that this method is robust and efficient and thus will provide a
      route for radiobromination of electron-deficient arenes and an alternative route
      for the synthesis of bromo-radiopharmaceuticals for biological evaluations.

PMID- 28512785
TI  - Clinical, immunologic, molecular analyses and outcomes of iranian patients with
      LRBA deficiency: A longitudinal study.
AB  - BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a
      combined immunodeficiency caused by mutation in LRBA gene. The patients have a
      variety of clinical symptoms including hypogammaglobulinemia, recurrent
      infections, autoimmunity, and enteropathy. METHODS: A total of 17 LRBA-deficient
      patients were enrolled in this longitudinal study. For all patients, demographic
      information, clinical records, laboratory, and molecular data were collected.
      RESULT: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency
      in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency
      in 11 (64.7%) patients. All patients had history of infectious complications;
      pneumonia was the most common (76.5%) occurring infection. A history of
      lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13
      (76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5),
      and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus
      treatment improved enteropathy of patients with remarkable success. The 20-year
      overall survival rate declined to 70.6%. CONCLUSION: LRBA deficiency has a very
      broad and variable phenotype and should be considered, especially in children
      with early-onset hypogammaglobulinemia, severe autoimmune manifestations,
      enteropathy, lymphoproliferation, and recurrent respiratory tract infections.

PMID- 28512786
TI  - A Single-Molecular AND Gate Operated with Two Orthogonal Switching Mechanisms.
AB  - Single-molecular electronics is a potential solution to nanoscale electronic
      devices. While simple functional single-molecule devices such as diodes,
      switches, and wires are well studied, complex single-molecular systems with
      multiple functional units are rarely investigated. Here, a single-molecule AND
      logic gate is constructed from a proton-switchable edge-on gated
      pyridinoparacyclophane unit with a light-switchable diarylethene unit. The AND
      gate can be controlled orthogonally by light and protonation and produce desired
      electrical output at room temperature. The AND gate shows high conductivity when
      treated with UV light and in the neutral state, and low conductivity when treated
      either with visible light or acid. A conductance difference of 7.3 is observed
      for the switching from the highest conducting state to second-highest conducting
      state and a conductance ratio of 94 is observed between the most and least
      conducting states. The orthogonality of the two stimuli is further demonstrated
      by UV-vis, NMR, and density function theory calculations. This is a demonstration
      of concept of constructing a complex single-molecule electronic device from two
      coupled functional units.

PMID- 28512787
TI  - Corrigendum.

PMID- 28512788
TI  - Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after
      autologous stem cell transplant in the current era of novel therapeutics: A
      retrospective analysis.
AB  - Patients with relapsed/refractory Hodgkin lymphoma (RR-HL) who progress or
      relapse following autologous stem cell transplantation (ASCT) have historically
      had a poor prognosis. Several novel agents, particularly brentuximab vedotin,
      have shown efficacy in this setting. However, there remains a paucity of data
      characterizing outcomes outside of clinical trials and how these novel agents
      have impacted prognosis in general population of patients with RR-HL. Here, we
      conducted a retrospective analysis to evaluate outcomes in 87 patients with RR-HL
      with relapse post-ASCT. Treatment with novel agents (including brentuximab
      vedotin) was associated with significant improvement in median overall survival
      (OS) compared to patients who did not receive novel agents (85.6 vs 17.1 months;
      P < .001). Additional factors associated with improved OS in univariate analysis
      include treatment with radiation therapy post-ASCT (34.1 vs 17.0 months; P =
      .015), chemosensitivity (i.e., relapsed compared to primary refractory disease;
      51.8 vs 25.6 months; p = 0.013), initial response to ASCT (i.e., CR/PR compared
      to SD/PD; 46.1 vs 20.4 months; P = .011), and transplantation in 2010 and later
      compared to prior to 2010 (not reached vs 24.5 months; P = .025). The current
      study demonstrates markedly improved OS in RR-HL patients treated with novel
      therapeutics and lends "real world" credence to the role of these agents in
      improving outcomes in the current era.

PMID- 28512790
TI  - Ultrastructural changes of the glomerular basement membrane... unmasked by C4d
      staining.

PMID- 28512792
TI  - Expression of aquaporin 4 in the chicken ovary in relation to follicle
      development.
AB  - In the mammalian ovary, aquaporins (AQPs) are thought to be involved in the
      regulation of fluid transport within the follicular wall and antrum formation.
      Data concerning the AQPs in the avian ovary is very limited. Therefore, the
      present study was designed to examine whether the AQP4 is present in the chicken
      ovary, and if so, what is its distribution in the ovarian compartment of the
      laying hen. Localization of AQP4 in the ovarian follicles at different stage of
      development was also investigated. After decapitation of hens the stroma with
      primordial follicles and white (1-4 mm), yellowish (4-8 mm), small yellow and the
      three largest yellow pre-ovulatory follicles F3-F1 (F3 < F2 < F1; 20-36 mm) were
      isolated from the ovary. The granulosa and theca layers were separated from the
      pre-ovulatory follicles. The AQP4 mRNA and protein were detected in all examined
      ovarian compartments by the real-time PCR and Western blot analyses,
      respectively. The relative expression of AQP4 was depended on follicular size and
      the layer of follicular wall. It was the lowest in the granulosa layer of pre
      ovulatory follicles and the highest in the ovarian stroma as well as white and
      yellowish follicles. Along with approaching of the largest follicle to ovulation
      the gradual decrease in AQP4 protein level in the granulosa layer was observed.
      Immunoreactivity for AQP4 was present in the granulosa and theca cells (theca
      interna >= theca externa > granulosa). The obtained results suggest that AQP4 may
      take part in the regulation of water transport required for follicle development
      in the chicken ovary.

PMID- 28512793
TI  - 5-Azacytidine-mediated hMSC behavior on electrospun scaffolds for skeletal muscle
      regeneration.
AB  - Incomplete regeneration after trauma or muscular dysfunction is a common problem
      in muscle replacement therapies. Recent approaches in tissue engineering allow
      for the replication of skeletal muscle structure and function in vitro and in
      vivo by molecular therapies and implantable scaffolds which properly address
      muscle cells toward myotube differentiation and maturation. Here, we investigate
      the in vitro response of human mesenchymal stem cells (hMSC) on electrospun
      fibers made of polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to
      evaluate how fibrous network may influence the therapeutic effect of drug during
      in vitro myogenesis. Biological studies demonstrate the ability of hMSCs to
      differentiate in mature myofibers in supplemented (myogenic) and, preferentially,
      in 5-AZA-enriched culture. PCL electrospun fibers amplify the 5-AZA capability to
      induce a low proliferation rate in hMSC, thus promoting hMSC differentiation (MTT
      assay). Qualitative (Azan Mallory stain, immunofluorescence assay, SEM analyses)
      and quantitative (ELISA test) assays confirm the synergistic contribution of PCL
      electrospun fibers and 5-AZA on in vitro myotubes formation and maturation. This
      result is also confirmed by the expression of muscle-specific proteins related to
      the myogenic mechanisms in the presence of other muscle inductive signals (i.e.,
      oxytocin, Tweak). Hence, we suggest the use of PCL electrospun fibers as
      interesting preclinical model to explore the effect of drugs and
      chemotherapeutics administration after damaged muscle resection. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2551-2561, 2017.

PMID- 28512794
TI  - Free and total plasma concentrations of elvitegravir/cobicistat during pregnancy
      and postpartum: a case report.

PMID- 28512796
TI  - Poster - Thurs Eve-11: Quantitative imaging of 213Bi alpha-emitter with a beta
      imager.
AB  - Targeted alpha-particle emitter therapy is emerging as a promising approach for
      treating metastatic cancer. An understanding of the biodistribution of targeted
      alpha-emitters at the cell level is important in evaluating potential efficacy
      and toxicity. This is best accomplished by autoradiography of tissue samples, ex
      vivo. We have investigated the feasibility of using a high resolution,
      quantitative beta-imager (Biospace Mesures beta-Imager) to detect the short-lived
      alpha-particle emitter, Bismuth-213 (213Bi). The advantages of this detector
      include: shorter acquisition time than film-based autoradiography, which is
      critical for an isotope with such a short half-life; high resolution; and data
      acquisition in list mode. While our interest in 213Bi lies in the alpha, the
      decay chain includes high energy beta- particles, enabling this study. Published
      studies using the beta-Imager show predominantly qualitative results, with the
      quantitative depending on long exposure time or direct comparisons. At low count
      rate the detector auto-regulates by varying the HV, directly affecting the
      results. We imaged a phantom prepared from 213Bi in 5% gelatin. We plot only the
      results in a narrow HV range and fit an exponential decay function to obtain a
      half-life close to the expected value. We plot the ratio of the exponential fit
      to the measured count rate value against HV for all count rates and find a
      functional correlation between HV and count rate. A similar correction for gas
      flow ratio variations is also applied. As the remaining fluctuations conform to
      Gaussian statistics, this suggests that we have successfully calibrated 213Bi for
      future studies.

PMID- 28512791
TI  - Peptide-Functionalized Fluorescent Particles for In Situ Detection of Nitric
      Oxide via Peroxynitrite-Mediated Nitration.
AB  - Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role
      in modulating physiological homeostasis across multiple biological systems. NO
      dysregulation is linked to the pathogenesis of multiple diseases; therefore, its
      quantification is important for understanding pathophysiological processes. The
      detection of NO is challenging, typically limited by its reactive nature and
      short half-life. Additionally, the presence of interfering analytes and
      accessibility to biological fluids in the native tissues make the measurement
      technically challenging and often unreliable. Here, a bio-inspired peptide-based
      NO sensor is developed, which detects NO-derived oxidants, predominately
      peroxynitrite-mediated nitration of tyrosine residues. It is demonstrated that
      these peptide-based NO sensors can detect peroxynitrite-mediated nitration in
      response to physiological shear stress by endothelial cells in vitro. Using the
      peptide-conjugated fluorescent particle immunoassay, peroxynitrite-mediated
      nitration activity with a detection limit of ~100 * 10-9 m is detected. This
      study envisions that the NO detection platform can be applied to a multitude of
      applications including monitoring of NO activity in healthy and diseased tissues,
      localized detection of NO production of specific cells, and cell
      based/therapeutic screening of peroxynitrite levels to monitor pronitroxidative
      stress in biological samples.

PMID- 28512795
TI  - Influence of primary site on metastatic distribution and survival in stage IV
      colorectal cancer.
AB  - BACKGROUND: To assess pattern distribution and prognosis of the three anatomical
      entities of metastatic colorectal cancer, and influence of treatment of
      metastases on survival. METHODS: Patients presenting with stage IV colorectal
      cancer (synchronous group), or who developed metastatic recurrence (metachronous
      group) after initial curative treatment between January 2005 and August 2015 were
      reviewed. Right sided (cecum to transverse colon), left sided (splenic flexure to
      sigmoid colon) and rectal cancers were identified. Distribution of metastases
      were noted as hepatic, lung or peritoneal. RESULTS: Of 374 patients, 276 were
      synchronous, 98 were metachronous. Metachronous group had a better 3-year
      survival (54%, 95% CI: 42-64 versus 33%, 95% CI: 27-39, log rank P = 0.0038).
      There were equal numbers of right (n = 119), left (n = 115) and rectal cancers (n
      = 140). Rectal cancers had a higher metastatic recurrence, yet demonstrated
      better 3-year survival (right colon 45%, 95% CI: 19-67, left colon 49%, 95% CI:
      27-68, rectum 59%, 95% CI: 42-72, P = 0.39) due to higher proportions of
      metachronous patients undergoing treatment for metastases (40 versus 14%). Over
      half of all organ metastases spread to liver, with equal distribution from all
      three anatomical groups. Rectal cancers showed highest preponderance for lung
      metastases. CONCLUSION: Rectal cancers have a higher chance of recurring, with a
      higher metastatic rate to the lung, yet demonstrate better survival outcomes in
      metastatic colorectal cancer, reflecting the benefit of intervention for
      metastases.

PMID- 28512797
TI  - Poster - Thurs Eve-22: Image guided radiation therapy for lung cancer.
AB  - OBJECTIVE: To determine the geometric accuracy of conventional and stereotactic
      lung radiotherapy using cone-beam CT image guidance, and assess the efficacy of
      these image-guided radiation therapy (IGRT) processes. MATERIALS AND METHODS:
      IGRT was first used for our stereotactic lung program, where high geometric
      accuracy is required to deliver high doses in few fractions. The initial
      positional accuracy for 47 patients was assessed by registering daily CBCT to the
      planning CT; the patient position was corrected when the CBCT indicated
      discrepancies > +/- 3 mm in any direction. For 19 of these patients, a second
      CBCT was acquired to assess the residual error. IGRT was also used to assess the
      initial and residual errors for lung cancer patients treated conventionally with
      (14 pts; 584 CBCT) and without (25 pts; 1032 CBCT) a remote-controlled treatment
      couch. Systematic (Sigma) and random (sigma) positional errors were assessed for
      these three groups. RESULTS: For stereotactic lung patients, Sigma and sigma
      ranged between 4.1 and 6.1 mm. IGRT reduces these errors to 1.2-1.9 mm, raising
      the proportion of patients within +/- 3 mm from 16% to 82%. For conventional lung
      cancer patients, Sigma and sigma ranged between 1.4 and 3.8 mm, and IGRT raises
      the proportion of patients within +/- 3 mm from 27% to 67%, with the remote
      controlled couch further improving this proportion to 84%. CONCLUSION: IGRT
      clearly confirms the high geometric accuracy required for stereotactic lung
      patients. This new paradigm has been transported to patients with locally
      advanced lung cancer, with similar accuracy.

PMID- 28512798
TI  - Sci-Thurs PM: Delivery-05: One year of learning from incidents.
AB  - The aim of this study is to quantify the effect of an incident learning system in
      radiation therapy. The system is designed to detect all occurrences of "an
      unwanted or unexpected change from a normal system behaviour that causes or has
      the potential to cause an adverse effect to persons or equipment". Our
      application to radiation therapy defines 5 incident types, four levels of
      severity and four work domains where errors discovered during routine quality
      assurance within each domain were not classified as incidents. During 2007, we
      recorded, corrected, investigated, determined root cause and learned from 657
      incidents. The vast majority of these incidents were classified as potential
      minor clinical incidents having little or no impact on patient treatment. The
      value of the system lies in the application of the learning portion of the
      investigation. We demonstrated a dramatic reduction in the rate of more severe
      incidents by the implementation of several simple tools. Our results also show a
      reduction of incidents on accelerators treating essentially a single disease
      site. The only treatment unit treating with both image guidance and intensity
      modulation recorded the fewest incidents while the cobalt unit with the least
      technological assistance recorded three times the average treatment unit
      incidents with a higher severity. Additionally, although the rate of incidents at
      the point of treatment delivery was low, the impact of those incidents was
      substantially higher than that of incidents originating during treatment
      planning. This system has proven to be a powerful program management tool.

PMID- 28512799
TI  - Poster - Thurs Eve-33: Initial implementation of a novel, measurement-based IMRT
      QA method.
AB  - Current measurement-based QA for IMRT typically involves a composite dose
      delivery to a phantom. However, this approach does not allow a direct dosimetric
      evaluation of the delivered treatment with respect to the patient anatomy. In
      this work we implement a novel, measurement-based IMRT QA method which provides
      an accurate reconstruction of the 3D-dose distribution in the patient model. The
      RPC Head&Neck phantom and two clinical prostate cases have been examined to date.
      Step & shoot plans were developed satisfying required dose metrics. A 2D-array of
      dose chambers (MatriXX, IBA Dosimetry) was mounted on a linear accelerator to
      capture delivered fluence. The measurement data were read directly by the control
      software (COMPASS, IBA Dosimetry), which also provides the ability to import
      patient plan data from the TPS. The COMPASS software also includes a dose
      calculation engine and head fluence model and requires beam commissioning
      procedures analogous to those of a TPS. Reconstructed doses and DVHs were
      compared to those calculated by the TPS. The beam model in the COMPASS software
      was able to predict percentage depth dose and X and Y profiles for MLC-defined
      apertures ranging from 1*1-20*20 cm?2 to within 1.5% (depth-dose), 2.0% (in-field
      profiles), and 2.5% (out-of-field profiles). Reconstructed doses in the test
      plans were mostly within 2% of those in the TPS. DVHs compared to <1.2%.
      Reconstructed doses were overlaid on CT data and contoured structures, to enable
      a clinically useful understanding of discrepancies as compared to the TPS plan.
      Research partially sponsored by IBA Dosimetry.

PMID- 28512800
TI  - Poster - Thurs Eve-04: Mathematical modeling of liver metastases tumour growth
      and control with radiotherapy.
AB  - Generating an optimized radiation treatment plan requires understanding the
      factors affecting tumour control. Mathematical models of tumour dynamics may help
      in future studies of factors predicting tumor sensitivity to radiotherapy. In
      this study, a time-dependent differential model, incorporating biological cancer
      markers, is presented to describe pre-treatment tumour growth, response to
      radiation, and recurrence. The model uses Gompertzian growth to model pre
      treatment tumour growth. The effect of radiotherapy is handled by a realistic
      cell-kill term that includes a volume-dependent change in tumour sensitivity.
      Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As
      proof-of-concept, we examined the fit of the model's prediction using various
      liver enzyme levels as markers of metastatic liver tumour growth in a liver
      cancer patient. Enzyme data were derived from repeated serum blood tests, and
      radiation treatment-related data were retrieved from the patient's chart. A
      tumour clonogen population model was formulated. Each enzyme was coupled to the
      same tumour population, and served as surrogates of the tumour. This dynamical
      model was solved numerically and compared to the measured enzyme levels. By
      minimizing the mean-squared error of the model enzyme predictions, we determined
      the following tumour model parameters: growth rate prior to treatment was 0.7%
      per day; the fractional radiation cell kill for the prescribed dose was 60% per
      day; and tumour repopulation rate was 3.5% per day. These preliminary results
      provided the basis to test the model in a larger series of patients, to apply
      biological markers for improving the efficacy of radiotherapy by determining the
      underlying tumour dynamics.

PMID- 28512801
TI  - Poster - Thurs Eve-15: Comparison of Cobalt-60 and 6 MV linac based tomotherapy:
      A prostate case study.
AB  - Previous work reported by us has shown the potential for Cobalt-60 (Co-60)
      tomotherapy for sites with small separations such as in head and neck site. In
      this work we extend our investigations by comparing tomotherapy plans for the
      treatment of a typical prostate cancer obtained for 6 MV and Co-60 beams. Beam
      collimation was provided by the MIMiC(r) (NOMOS Corporation, Sewickly, PA) multi
      leaf collimator (MLC). Both plans used 21 beam angles, each utilizing the central
      10 leaf-pairs of the MLC for intensity modulation. An in-house inverse treatment
      planning program, based on the active-set conjugate gradient method, was used for
      dose-volume optimization. BEAMnrc and DOSXYZnrc Monte Carlo simulated beam and
      dose data, including inhomogeneity corrections, were used to calculate the
      optimized tomotherapy dose distributions. Prostate, rectum, and external body
      contours were outlined and dose-volume optimization objectives were set to
      deliver a minimum of 95% and a maximum of 105% of the 76 Gy dose prescription to
      the prostate and limiting only 20% of the rectum volume to receive ? 70 Gy. A
      quantitative analysis of the dose distributions and dose-area histograms show
      that both Co-60 and 6 MV plans achieve the initial objectives for target
      (prostate) and organ at risk (rectum). Although the dose to the body and rectum
      for Co-60 is slightly higher than that for 6 MV, it satisfies the plan objectives
      based on the clinical dose tolerance. Our results demonstrate that Co-60 based
      tomotherapy can provide clinically competitive dose distributions for the
      treatment of prostate cancer.

PMID- 28512802
TI  - Poster - Thurs Eve-26: Influence of MLC leaf edge and tongue and groove effect on
      IMRT dose distributions.
AB  - An important consideration when using multileaf collimators (MLCs) for IMRT
      delivery is the correct account of leaf edge effects. To study these effects, two
      maps were constructed from a clinical beam's step and shoot delivery sequence: a
      time-weighted leaf edge position (LEP) map where the pixel intensity was
      proportional to the length of time that a leaf edge defined the edge of any
      segment within the field, and a (TG) map where pixel intensity was proportional
      to the length of time that adjacent segments matched along a leaf edge. We
      investigated the correlation between LEP or TG maps with dose error maps
      (obtained by subtracting calculated from either measured (CM) or from re
      calculated (CC) data). Re-calculated data were obtained by modifying selected MLC
      photon modeling parameters from their commissioned values. We calculated the
      correlation coefficient between corresponding regions of CM and CC maps with TG
      and LEP maps. A NAT analysis of the CM maps indicated that the NAT index was
      minimized for tongue and groove width at the commissioned value of 0.1cm. A
      higher correlation coefficient was seen between CM and LEP maps (0.62+/-0.11)
      than between CM or CC and TG maps across all MLC modeling parameters used. The
      low correlation between both LEP or TG maps and CC maps suggests that the higher
      correlation observed between both LEP or TG maps and CM maps cannot be attributed
      to the choice of MLC modeling parameters alone. Further work is needed to
      pinpoint the cause of this correlation.

PMID- 28512803
TI  - Sci-Thurs PM: Delivery-09: Improving megavoltage portal image contrast with low
      atomic number target materials.
AB  - PURPOSE: to investigate the impact of low atomic number (Z) targets and detector
      design on megavoltage (MV) portal image contrast. METHODS AND MATERIALS: two
      experimental beams were generated by replacing flattening filtration of a 2100EX
      linac with beryllium (Be) and aluminum (Al) targets and using the linac in 6 MeV
      electron mode. A standard MV contrast phantom was used to quantify planar image
      contrast for the standard 6MV and the 6MeVAl beam, incident on an amorphous
      silicon (a-Si) detector. Contrast versus separation for 6MV and 6MeV/Al was
      quantified using a 1 cm bone/solid water slab within increasing thicknesses of
      solid water. The Monte Carlo BEAMnrc/DOXYZnrc package was used to model beam
      generation and detection. The beam/detector model was validated with comparison
      to measured open field profiles. RESULTS: Low-Z target spectra differ
      significantly from the standard 6MV spectrum with Be-target and Al-target peaks
      at ~ 25keV and ~50keV, respectively. Approximately 1/3rd of the photon population
      is below 60keV for the 4MeV/Be beam. Planar contrast is increased significantly
      over that of 6MV using low-Z targets, showing additional improvement with removal
      of the detector's copper build-up layer. Contrast decreases with increasing
      separation more rapidly for 6MeV/Al than for 6MV; however contrast for the former
      is superior over the full range of separation examined. CONCLUSIONS: Use of low-Z
      linac target materials improves MV image contrast. An additional advantage is
      realized by removing the copper layer from the a-Si detector. CONFLICT OF
      INTEREST: This research has been sponsored by Varian Medical Systems,
      Incorporated.

PMID- 28512804
TI  - Poster - Thurs Eve-37: Energy and irradiation modality independence of
      calibration coefficients for water equivalent plastic scintillation detectors in
      the megavoltage range.
AB  - PURPOSE: To demonstrate that the independence of the calibration coefficients of
      plastic scintillation detector (PSD) for both photon and electron beams in the
      megavoltage energy range. METHOD AND MATERIALS: The PSD consists in a small 1 mm
      diameter and 2 mm long plastic scintillating fiber made of a polystyrene core
      (BCF-12, Saint-Gobain, inc.). The scintillator was coupled to a 2 meters long non
      scintillating plastic optical fiber and a color CCD camera (Apogee instruments
      inc.) was used as photodetector. The calibration coefficients of the PSD where
      extracted for 6 MV, 23 MV photon beams and 9,12,15 and 18 MeV electron beams
      using a Farmer ionization chamber (Exradin). Complete removal of the Cerenkov
      radiation produced in the optical fiber was performed with a chromatic
      discrimination technique using the blue and green channel of the CCD camera. All
      measurements were performed according to the recommendations of the AAPM TG-51
      protocol for clinical dosimetry. RESULTS: The PSD exhibits a maximum deviation of
      less than 1.7 % (about the mean) of its calibration coefficients over the
      measured energy range for both irradiation modalities. CONCLUSION: The energy
      independence of the calibration coefficients for PSD was demonstrated
      experimentally for the first time for both photons and electrons. PSDs have the
      potential to simplify and improve accuracy of dose measurements in clinical
      situations where photons and electrons are both present in the beam such as
      electron contamination in photon beams or bremsstrahlung contaminated electron
      beams.

PMID- 28512805
TI  - Poster - Thurs Eve-08: Passive shimming optimization of a permanent magnet
      structure for a prototype coupled MRI-medical linear accelerator.
AB  - The ultimate goal of radiation therapy is to increase tumor control while
      reducing normal tissue complications. This is accomplished by conforming the
      radiation dose delivered to a patient to the tumor geometry, permitting the
      delivery of higher doses to the target volume while decreasing the dose in
      surrounding normal tissues. In order to best achieve this goal, our group is
      pursuing the design of a 0.2T biplanar magnetic resonance imager (MRI) coupled
      with a medical linear accelerator, which will be capable of performing real-time
      image guided radiotherapy. In a simplified design of the permanent magnet
      structure for this system, large paramagnetic plates which affect the
      characteristics of the magnetic field in the imaging volume are used to hold the
      magnetic material in place. Since the sole purpose of the MRI module of this unit
      is to provide geometrical information regarding the shape and position of the
      target volume during irradiation, obtaining distortion-free images is critical.
      In the present work, we seek a particular surface topology on the pole plates of
      the permanent magnet structure which minimizes the overall size of the pole
      plates while maximizing the homogeneity of the magnetic field in the imaging
      volume. A rose ring design is investigated with the aid of finite element
      analysis and the results indicate that a significant improvement in field
      uniformity is obtained as compared to the simplest design possible.

PMID- 28512806
TI  - Poster - Thurs Eve-19: IGRT QA for helical tomotherapy.
AB  - Helical tomotherapy (HT) with daily imaging using mega-voltage computed
      tomography for 3D image guided radiotherapy (IGRT). We present two techniques
      developed in our department to verify the integrity of the HT IGRT process. A
      phantom was constructed of two equally sized (5*10*10cm3 ) polystyrene blocks
      stacked on top of each other, each piece having a hole capable of receiving a
      small volume ionization chamber. A piece of Radiochromic film fits neatly in
      between the blocks. The phantom was CT scanned and the CT slices were transferred
      to the HT treatment planning system (TPS). The first procedure is used daily to
      test the image registration aspects of the IGRT process, and involves setting the
      phantom on the tomotherapy treatment unit table in an arbitrary position, imaging
      it, and performing image registration to determine what displacements are
      necessary to return the phantom to the planned position. A variation of this test
      is to place the phantom at a position incurring known displacements and ensuring
      the registration recognizes the shifts. The second procedure verifies the entire
      IGRT procedure, and includes the first procedure and the delivery of a treatment
      plan. An inverse plan is created to deliver simultaneously 2 and 3 Gy to 2 pre
      defined targets. The treatment plan can be setup as a QA plan in the TPS
      software, allowing for a detailed comparison of ion chamber measurements and film
      dosimetry to the planned dose distribution. We have found that these QA
      procedures adequately test the IGRT capabilities of our HT unit.

PMID- 28512807
TI  - Poster - Thurs Eve-30: Investigation of a patient immobilization system for
      breast tomotherapy.
AB  - Using tomotherapy to deliver adjuvant radiation therapy for breast cancer
      treatment requires more precise immobilization than can be achieved using gravity
      alone. We evaluated the use of a thermoplastic shell to immobilize the patient's
      torso during breast cancer treatment. To measure intrafraction breathing motion,
      4DCT scans were performed for eight post-lumpectomy or post-mastectomy breast
      cancer patients with the thermoplastic shell in place. The 4DCT scans were then
      analyzed to determine the magnitude of motion of the breast surface, chest wall,
      and heart over the breathing cycle. Maximum surface motion was typically less
      than 2mm, with a maximum of 4mm. Maximum displacement of the chest wall was less
      than 3mm with a maximum of 5mm in a single patient. Comparison with the setup
      errors recorded prior to repositioning the patients suggests that, with the
      thermoplastic shell in place, patient setup error will be a more significant
      source of uncertainty in patient position than breathing motion.

PMID- 28512808
TI  - Poster - Thurs Eve-21: Experience with the Velocity(TM) pre-commissioning
      services.
AB  - As the first Canadian users of the VelocityTM program offered by Siemens, we
      would like to share our experience with the program. The Velocity program
      involves the measurement of the commissioning data by an independent Physics
      consulting company at the factory test cell. The data collected was used to model
      the treatment beams in our planning system in parallel with the linac delivery
      and installation. Beam models and a complete data book were generated for two
      photon energies including Virtual Wedge, physical wedge, and IMRT, and 6 electron
      energies at 100 and 110 cm SSD. Our final beam models are essentially the
      Velocity models with some minor modifications to customize the fit to our liking.
      Our experience with the Velocity program was very positive; the data collection
      was professional and efficient. It allowed us to proceed with confidence in our
      beam data and modeling and to spend more time on other aspects of opening a new
      clinic. With the assistance of the program we were able to open a three-linac
      clinic with Image-Guided IMRT within 4.5 months of machine delivery.

PMID- 28512809
TI  - Sci-Thurs PM: Delivery-04: Comprehensive fluence model for absolute portal dose
      image prediction in IMRT pre-treatment verification.
AB  - Amorphous silicon (a-Si) electronic portal imaging devices (EPIDs) have been
      heavily investigated as treatment verification tools, with a particular focus on
      intensity modulated radiation therapy (IMRT). This verification could be
      accomplished through a comparison of measured portal images to predicted images.
      A general fluence determination for portal dose image prediction would be a great
      asset in order to model the complex modulation of IMRT. A physically-based
      parameter fluence model was developed by matching multi-leaf collimator defined
      predicted images to measured image profiles. The fluence model was composed of a
      focal Gaussian and extrafocal Gaussian-like source (Pearson VII). Specific
      aspects of the MLCs and secondary collimators were also modeled (eg. jaw and MLC
      transmission factors, MLC rounded leaf tips, tongue and groove effect, interleaf
      leakage, MLC offsets). The resulting calculated fluence was then convolved with
      Monte Carlo generated EPID-specific dose kernels to convert incident fluence to
      dose delivered to the EPID. Measured EPID data was obtained with an a-Si EPID for
      various MLC-defined fields (1*1 to 20*20 cm2 ) over a range of source-to-imager
      distances. These measured profiles were used to determine the fluence model
      parameters and the resulting model was tested on prostate and oropharyngeal IMRT
      fields. The model predicted the open-field profiles within 2%, 2mm, while the
      predicted IMRT fields were generally within 3%, 3mm for at least 96% of the
      pixels. This model demonstrates the necessary accuracy needed for IMRT portal
      dose image prediction in complex clinical examples (<3%, 3mm) and could be used
      for pre-treatment verification.

PMID- 28512810
TI  - Poster - Thurs Eve-32: Dose errors related to the treatment couch.
AB  - Modern radiotherapy linacs often use carbon fibre for their couch tops due to its
      radio translucent properties. Beam attenuation by the couches is often ignored
      during planning and MU calculation. This work examines beam attenuation and loss
      of "skin sparing" (dose build up region) when various photon beams transit either
      the MedTec (Siemens) or Medical Intelligence (Elekta) couches. Additionally,
      measured doses were compared to CMS treatment planning system (XiO version
      4.33.02) predictions. We found the two couches to have different structures,
      resulting in different attenuation signatures as a function of gantry angle. For
      normal beam incidence the Siemens and Elekta couches had radiological thicknesses
      of 4.5 mm and 6.0 mm, respectively. For a normal incidence 10*10 cm2 6MV beam the
      surface dose after couch transmission was 93% vs. 83% for Elekta and Siemens,
      respectively. Conversely, the increased mass on the lateral edge of the Siemens
      couch resulted in a maximum attenuation (6 MV 5*5 cm2 beams) of 8% compared to 5%
      by the Elekta couch. Incorporating the treatment couch as part of the patient
      planning CT allowed the CMS TPS model to calculate couch attenuation within 1% of
      measurement, except at the very edge of the Siemens couch, where the attenuation
      is strongly gantry angle dependent. The CMS beam model was also able to predict
      the loss of skin sparing within 1%. In conclusion, the two patient couches are
      different, but both can significantly affect patient dose which can be accounted
      for in the CMS TPS.

PMID- 28512811
TI  - Poster - Thurs Eve-03: Dose verification using a 2D diode array (Mapcheck) for
      electron beam modeling, QA and patient customized cutouts.
AB  - PURPOSE: To assess a diode detector array (MapCheck) for commissioning, quality
      assurance (QA); and patient specific QA for electrons. METHOD AND MATERIALS: 2D
      dose information was captured for various depths at several square fields ranging
      from 2*2 to 25*25cm2 , and 9 patient customized cutouts using both Mapcheck and a
      scanning water phantom. Beam energies of 6, 9, 12, 16 and 20 MeV produced by
      Varian linacs were used. The water tank, beam energies and fields were also
      modeled on the Pinnacle planning system obtaining dose information. Mapcheck,
      water phantom and Pinnacle results were compared. Relative output factors (ROF)
      acquired with Mapcheck were compared to an in-house algorithm (JeffIrreg). Inter-
      and intra-observer variability was also investigated Results: Profiles and %DD
      data for Mapcheck, water tank, and Pinnacle agree well. High-dose, low-dose
      gradient comparisons agree to within 1% between Mapcheck and water phantom. Field
      size comparisons showed mostly sub-millimeter agreement. ROFs for Mapcheck and
      JeffIrreg agreed within 2.0% (mean=0.9%+/-0.6%). CONCLUSION: The current standard
      for electron commissioning and QA is the scanning water tank which may be
      inefficient. Our results demonstrate that MapCheck can potentially be an
      alternative. Also the dose distributions for patient specific electron treatment
      require verification. This procedure is particularly challenging when the minimum
      dimension across the central axis of the cutout is smaller than the range of the
      electrons in question. Mapcheck offers an easy and efficient way of determining
      patient dose distributions especially compared to using the alternatives, namely,
      ion chamber and film.

PMID- 28512812
TI  - Poster - Thurs Eve-14: Linking IGRT data with dose calculation for prostate IMRT
      planning.
AB  - Internal organ motion was studied for 20 prostate patients who were treated with
      IGRT using MV EPI with three gold seeds implanted in the prostate. Prostate
      motion was determined from the gold seed displacement relative to bony anatomy
      between the EPI and the DRR fraction-to-fraction before any correction was
      applied. The patients were planned with a tight 2mm PTV margin for seven-beam
      IMRT with prescribed dose of 82 Gy. Treatment planning incorporating organ motion
      was done manually by convolving the static dose distribution with patient
      specific PDF. A Gaussian PDF is reasonable for modeling geometric uncertainties.
      In the anterior and superior directions, dose decreased more than 5% on the edge
      of PTV for 5% of the patients. While in inferior direction the dose decreased
      more than 5% on the edge of PTV for 15% of the patients. The PTV dose is lower
      than 95% prescription dose for 10% of the patient incorporating individual IGRT
      data. While for applying group PDF, the dose satisfied the minimum 95% of PTV
      dose, so group PDF should not be used for accurate treatment planning evaluation
      for individual patients. Static dose distribution is insufficient to assess PTV
      coverage. The inclusion of organ motion on dose distribution is required for
      close agreement between planned and delivered dose. The Gaussian PDF is patient
      specific and group PDF should not be used for accurate treatment planning
      evaluation for individual patients. Patient-specific PDF data should be used for
      re-planning to assess accuracy of delivered dose.

PMID- 28512813
TI  - Poster - Thurs Eve-25: Depth dependence of electron backscatter for electron
      radiotherapy: A Monte Carlo study.
AB  - The aim of this study is to investigate the depth dependence of electron
      backscatter from lead (Pb) for clinical electron beams using Monte Carlo
      simulations. Phase-space files for the 4 and 9MeV electron beams based on the
      Varian 21EX Linac were generated using the BEAMnrc code. A 3mm Pb layer was
      irradiated by the phase-space beams with 0.5 and 1cm depth of water on top.
      Electron energy spectra at different depths in water with and without the Pb
      layer were determined using the BEAMnrc code. For energy spectra of the 4 MeV
      beams with 0.5cm depth of water, electron backscatter was found at both the Pb
      water interface and 0.5cm of water over the Pb. However, electron backscatter
      almost disappeared at 0.5 and 1cm of water over the Pb, when 1cm depth of water
      was used. This is because the increased attenuations of the (1) 4MeV beam from
      the thicker water layer, and (2) electron backscatter in water above the Pb. For
      the 9MeV beams with 0.5cm depth of water, only slight electron backscatter was
      observed. More electron backscatter was found when 1cm depth of water was used.
      It is because the electron beam energy was reduced more due to the attenuation of
      the 1 cm depth of water compared to 0.5 cm. Since the electron energy spectrum
      varies with depth of water on top of the Pb layer, the electron backscatter
      depends very much on the thickness of water/water equivalent bolus/human tissue
      over the Pb shield in electron radiotherapy.

PMID- 28512814
TI  - Sci-Thurs PM: Delivery-08: Investigation of the source of RF noise from a
      modulator for an MR-linac project.
AB  - INTRODUCTION: The next significant step in the advancement of IGRT is the
      integration of an MRI with a linac. The MRI-linac will provide images with
      exquisite soft tissue contrast in real-time during treatment. A possible problem
      associated with the proposed integration is the RF noise generated by the linac.
      This noise could interfere with the received signals of the MRI producing
      deleterious effects in the image quality. The work herein is concerned with
      understanding the processes involved in the RF noise production and the magnitude
      and frequency of this RF noise in the modulator of a linac. MATERIALS/METHODS: A
      software programming environment, MultiSIM, was used to model the electronic
      components of a modulator. Several Current and Voltage waveforms from the
      modulator were measured with an oscilloscope and compared with the corresponding
      results from the modulator model for validation. Finally, RF noise generated by
      the modulator was measured using field probes, which permits the frequency
      components of the measured and simulated modulator waveforms to be compared with
      the measured RF noise. RESULTS/DISCUSSION: The modeled PFN charging current and
      voltage, and klystron current show good agreement with measurements, with the
      exception of the tail of the klystron voltage signal. Once the model has been
      validated in both the time and frequency domains, future work will entail
      predicting pulse shape changes when, and if, modifications to the modulator are
      made. Specifically, modifications will be made which shift and/or reduce the RF
      noise in the frequency range of interest for a 0.2T MRI.

PMID- 28512815
TI  - Poster - Thurs Eve-36: Use of multileaf collimator as a replacement of physical
      missing tissue compensator.
AB  - Missing tissue compensators are used to improve dose uniformity for some patients
      undergoing radiation therapy. Currently, our practice is to machine compensators
      out of lead alloy plate. Replacing this physical filter with a segmented
      multileaf collimator (MLC) delivery sequence is beneficial in terms of work flow
      and delivery efficiency. The purpose of this work is to compare the dose
      uniformity achieved by fields that are either (A) conventionally compensated,
      compensated by segmenting the physical compensator thickness map into either (B)
      step-and-shoot or (C) dynamic MLC delivery sequences using an in-house sequencer,
      (D) compensated using Pinnacle sequencer, or (E) compensated using IMRT
      optimization. A computer program was developed to construct both step-and-shoot
      and dynamic MLC sequence files from mechanical thickness maps of our current
      compensators. In addition, the Pinnacle sequencer and IMRT optimization were used
      to generate step-and-shoot MLC sequences. Planar doses were measured for each at
      the isocenter depth with an ion chamber array to compare the five methods. A
      comparison of the relative dose distribution shows that the compensation achieved
      by method (E) is in close agreement with that achieved using method (A), that is,
      dose uniformity within 4%. Method (D) resulted in the shortest delivery time and
      achieved dose uniformity to within 5%. Methods (B) and (C) need additional
      refinement to be of practical use. The results support the feasibility of
      replacing physical compensators with MLC delivery sequences. Compensation by MLC
      segments provides more flexibility and efficiency in design and delivery than by
      physical compensators while maintaining or improving the uniformity of dose to
      the plane of compensation.

PMID- 28512816
TI  - Poster - Thurs Eve-07: The dosimetric consequences of MLC position inaccuracy in
      IMRT.
AB  - The Multileaf Collimator (MLC), the most widely used means of intensity
      modulating beams for IMRT, is subject to random and systematic errors in leaf
      positions that may compromise the treatment quality. This work is a simulation
      study of the effect of random and systematic errors in leaf position on delivered
      dose distributions. The dosimetric effects of random errors of up to 2 mm and
      systematic errors (+/-1mm in 2 banks, +/-0.5mm in 2 banks and 2mm in 1 bank of
      leaves) were analysed for a typical head and neck IMRT plan and a typical
      prostate IMRT plan. Dose Volume Histograms and Equivalent Uniform Doses (EUD) of
      the target volumes, bladder and rectum for the prostate plan and brainstem,
      larynx, parotids and spinal cord for the head and neck plan were calculated with
      and without MLC positioning errors and compared. The results show that if we
      adopt a 2% change in EUD of the target and 2 Gy for the OARs as acceptable levels
      of uncertainty in dose due to MLC effects only, then random errors of up to 2mm
      may be tolerated but systematic errors in leaf position will need to be limited
      to 0.5mm. Our study provides guidance, based on a surrogate of clinical outcome,
      for the development of quality control standards for multileaf collimators.

PMID- 28512817
TI  - Poster - Thurs Eve-18: Performance evaluation of MV CT imaging on the HI ART II
      tomotherapy unit.
AB  - The HI-ART II unit (TomoTherapy Inc., Madison WI) is a modality used by the
      London Regional Cancer Program (LRCP) for radiation therapy. This machine uses
      the same source of Megavoltage energy radiation to image (3.5 MV) and to treat
      (6MV) patients, combining the functionality of a traditional linear accelerator
      and CT simulator into one unit. Thus, it is possible to assess patient
      positioning and adjust for anatomy changes just prior to radiation therapy.
      Unfortunately, at MV energy levels, the physics of radiation interaction limits
      image quality, and gives rise to an inherent dose limitation concern that
      enhances noise levels. Therefore, we propose to quantify the image quality
      produced by the HI-ART II unit using techniques established for kVCT scanner
      technology. Our study involved the use of three standard phantoms to test image
      resolution, noise, uniformity, and linearity for a 512 * 512 reconstruction
      matrix and three scan pitch settings (0.8, 1.6, and 2.4). Results follow:
      linearity between MV CT number versus relative electron density was observed,
      noise calculations ranged from 2.15-2.51%, and a distinct central artifact was
      revealed during uniformity testing. The linearity between MV CT number versus
      relative electron density implies that MV CT images are highly suitable for dose
      calculations. MV CT image quality of uniform phantoms were acceptable and
      demonstrated noise levels higher than those produced by kVCT simulators. Further
      study is necessary to correct for the central artifact in MV CT images.

PMID- 28512818
TI  - Poster - Thurs Eve-29: Real-time tumour tracking and dose adaptation utilizing 4D
      MR images.
AB  - Magnetic Resonance Imaging (MRI) is known to be the best imaging modality for
      soft-tissue delineation. We will exploit this feature to develop and test a real
      time tumour tracking and dose adaptation algorithm based on 4D MR images, such as
      we hope to obtain using a Linac-MR system under development by our research
      group. We have developed algorithms capable of auto-contouring and tracking the
      motion of tumours in pseudo real-time from 4D MR image sets acquired 4 times per
      second. To compensate for the time delays between imaging, image processing, the
      mechanical movement of Linac, and the actual treatment, an algorithm capable of
      predictively modeling tumour position based on 4D MR images, such as would be
      acquired just prior to patient treatment, is being developed. Based on these, an
      algorithm able to adjust Multileaf Collimator (MLC) movement and beam intensity
      depending on the position, depth, and density of tissue overlying the tumour as a
      function of time is under development. Our initial results, in which we used 4D
      MR images acquired from a 3T MR scanner with a Steady State Free Precession
      (SSFP) image sequence, demonstrated the feasibility of real-time tumour
      contouring and tracking. By using an in-house built MR compatible motion phantom
      and the same scanner with a Balanced Full Field Echo (BFFE) image sequence, we
      succeeded in acquiring dynamic MR images, and we confirmed the promising
      capability of our prediction algorithm, which can infer the position of tumour
      0.25 seconds in advance.

PMID- 28512819
TI  - Sci-Thurs PM: Delivery-12: Correction and calibration of megavoltage cone-beam CT
      images for the calculation of the dose of the day.
AB  - PURPOSE: To show that accurate dose calculations can be achieved with megavoltage
      cone-beam CT (MVCBCT) images of head-and-neck (H&N) and prostate sites, allowing
      the verification of the daily dose distribution received by these patients.
      METHOD AND MATERIALS: Corrections for the cupping and missing data artifacts seen
      on MVCBCT images were developed for both H&N and pelvic imaging. MVCBCT images of
      six H&N and two prostate patients were acquired weekly during the course of their
      treatment. Several regions of interest were contoured including: the prostate and
      rectum and the spinal cord and parotids. Dose calculation was performed with the
      MVCBCT images using the plan beams. Variations from treatment plan dosimetric
      endpoints were analyzed. RESULTS: Dose calculations with kVCT and corrected
      MVCBCT images of the H&N (pelvic) regions show standard deviations of 1.9%
      (0.6%). The mean dose to the right parotid of H&N patients had an average
      increase of 18% during treatment. The maximum dose to 1% of the spinal cord went
      up by 2% on average. For prostate patients on one fraction the dose received by
      95% of the prostate diminished by 3%. One patient had an average increase of 3.6%
      of the maximum dose received by 1% of the rectum. CONCLUSION: MVCBCT can be used
      to verify daily dose distributions for H&N and prostate patients. An increase in
      the mean dose to normal tissues was observed during H&N treatment. Underdosage of
      the prostate and the dosimetric consequences of volume changes in rectum and
      bladder were observed. Research supported by Siemens.

PMID- 28512820
TI  - Poster - Thurs Eve-31: Clinical implementation and experience with EPID-based
      precision isocentre localization.
AB  - Modern linear accelerators contain multiple isocentres, defined by the mechanical
      motions of gantry, collimator and table. Isocentre localization for these motions
      has been performed using film and manual evaluations which have difficulty in
      relating the individual motions. To address these limitations, we have developed
      an EPID based technique to measure the isocentre position for each of the
      treatment unit motions. This technique uses the projected position of a radio
      opaque marker at the isocentre in a series of MV images to determine the motion
      of the isocentre. This analytical procedure has been implemented in the clinic
      using a MatLab code to automatically analyze images and determine both the
      isocentre position and motion about the mean for each of gantry, collimator and
      table. Results of isocentre measurements for 18 machines from 2 different vendors
      at 2 separate clinics are reported. These measurements show that while the
      position of the mean isocentres are contained within a 2mm sphere, combinations
      of gantry, table and collimator rotations can be found that result in treatment
      isocentres more than 2mm apart. Results for a treatment unit, which underwent a
      recent equipment upgrade, are also presented that show a small change in the
      location of the gantry relative to the table isocentre. The implementation of
      this of isocentre localization technique has provided important clinical
      information which can be efficiently completed in less than an hour. This
      information is an important consideration in monitoring the changes and in
      assessing the treatment precision that can be obtained.

PMID- 28512821
TI  - Poster - Thurs Eve-02: 3 dimensional ultrasound-guided breast brachytherapy.
AB  - Breast cancer is one of Canada's leading causes of death, taking the lives of
      approximately 5000 people annually. Breast-conserving tumour excision, or
      lumpectomy followed by radiation therapy is becoming an increasingly common
      treatment method for smaller tumours. High dose rate (HDR) brachytherapy is a
      precise form of radiation delivery following surgery involving the delivery of
      radiation dose through an HDR afterloader attached to catheters inserted into the
      breast. Currently, a CT scan of the patient is taken to properly reconstruct the
      tumour and guide catheter insertion. We propose to use our three-dimensional
      ultrasound (3DUS) scanner as the primary treatment planning device, eliminating
      the need for a CT scan. This would greatly increase patient comfort along with
      saving time and money. We have designed and constructed a 3DUS scanner
      specifically to be used in breast brachytherapy. It attaches to a Kuske breast
      application kit already used in the clinic. Software to view 3DUS images produced
      by the device is already being used, and needle guidance software is currently
      being developed. Laboratory tests on agar phantoms are set to begin shortly to
      evaluate the precision of the device and perform brachytherapy catheter insertion
      simulations. When the results of these tests are satisfactory, a full
      brachytherapy procedure will be performed in Quebec City using the 3DUS scanner.

PMID- 28512822
TI  - Poster - Thurs Eve-13: Modeling the effect of organ motion on cumulative rectal
      dose using EUD.
AB  - A rigid body model and electronic serial portal imaging (EPI) data were used to
      generate the cumulative dose distribution for the rectum incorporating organ
      motion during IMRT. The impact of rectal motion was assessed via NTCP and TCP
      based on equivalent uniform dose per fraction (EUDf ). The rectal positional
      variations were measured fraction-to-fraction from MV EPI for 20 prostate
      patients implanted with gold seeds. Five-field (5F) and seven-field (7F) IMRT
      plans for prostate patients were constructed with prescribed dose 78 Gy/39
      fractions using a Pinnacle3 treatment planning system. EUD increased in 45% of
      the patients with greater than 2.5% increase for 5% of the patients. While EUD
      decreased in 55% of the patients with greater than 2.5% decrease for 10% of the
      patients. The amplitudes of EUDf increase and decrease are correlated with the
      dose gradient. Higher dose gradients lead to higher rectal EUDf change. The
      rectal NTCP decreases for half of the patients and increases for the other for
      both 5F and 7F plans. The NTCP decreased with the increasing of dose gradient
      between the prostate and rectum for 5F and 7F IMRT plans. The correlation
      coefficient for the rectal NTCP and the dose gradient is - 0.71. The increase or
      decrease of rectal cumulative dose depends on the dose gradient, motion amplitude
      and frequency in AP direction. EUDf is a useful QA parameter for interpreting the
      biological impact of geometric uncertainties on the static dose distribution.
      Rectal NTCP is patient dependent and must be determined individually.

PMID- 28512823
TI  - Poster - Thurs Eve-24: Dosimetry study on the penumbra region for the irregular
      MLC fields with stepping patterns.
AB  - The aim of this study is to investigate the dosimetric effect in the penumbra
      region for the multi-leaf collimator (MLC) fields with stepping patterns. Various
      irregular MLC fields with different stepping patterns were designed. Radiographic
      films were used to measure the beam profiles (cross-plane (X1-X2 jaw) and in
      plane (Y1-Y2 jaw)) for different MLC field configurations of varying lengths of
      protruded leaves adjacent (on one or both sides) to the beam profile axis. 6 MV
      photon beams produced by the Varian 21 EX linear accelerator with 120-leaf
      Millennium MLC were used. The results showed that the penumbra widths (10% - 90%)
      of the profiles (cross-plane) with 0.5 cm gap width increased with the protruded
      lengths of the neighbouring leaves, while the penumbra widths did not vary too
      much for the larger gap widths of 1 cm and 1.5 cm. The neighbouring leaf's
      influence on the profile was very insignificant, when the distance between the
      profile and neighbouring leaf edge was larger than 1 cm. Moreover, when both the
      upper and lower portions of leaves were moved out forming a gap for the profile,
      the dose at the "edge" region was decreased by about 20% and 6% when the
      protruded lengths of the leaves were 0.5 cm and 1 cm, respectively. It is
      important to understand the dosimetric effect in the penumbra region for
      irregular MLC fields with stepping leaf patterns, especially during the
      commissioning process for the conformal external beam and intensity modulated
      radiation therapy.

PMID- 28512824
TI  - Sci-Thurs PM: Delivery-07: Evaluation of prospects to use daily megavoltage CT
      studies for adaptive radiotherapy.
AB  - PURPOSE: To evaluate gross tumor volume (GTV) changes for non-small cell lung
      cancer (NSCLC) patients using daily megavoltage CT (MVCT) studies acquired before
      each treatment fraction on helical tomotherapy, and to relate the potential
      benefit of adaptive image-guided radiotherapy to changes in GTV. METHODS: 17
      patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for
      NSCLC at London Regional Cancer Program from December 2005 to March 2007. The GTV
      was contoured on the daily MVCT studies of each patient. Adapted plans were
      created using merged MVCT-kVCT image sets to investigate the advantages of
      replanning for patients with differing GTV regression characteristics. RESULTS:
      The average GTV change observed over 30 fractions was -38%, ranging from -12 to 
      87%. No significant correlation was observed between GTV change and patient's
      physical or tumor features. The pattern of GTV changes of the 17 patients could
      be broadly divided into 3 groups with distinctive potential for benefit from
      adaptive planning. CONCLUSIONS: GTV changes are difficult to predict
      quantitatively based on patient or tumor characteristics. If changes do occur,
      there are points in time during the treatment course when it may be appropriate
      to adapt the plan to improve sparing of normal tissues. If the GTV decreases by
      greater than 30% at any point in the first twenty fractions of treatment,
      adaptive planning is appropriate to further improve the therapeutic ratio.

PMID- 28512825
TI  - Poster - Thurs Eve-35: Error reduction in variable angle implant reconstruction
      by optimization of imaging geometry.
AB  - Movement towards intraoperative dosimetric analysis of permanent seed
      brachytherapy implants has driven seed localization techniques that may be
      applied in an operating suite. Variable angle reconstructions with a C-arm are a
      widely available, cost effective and easily integrated solution but are subject
      to mechanical limitations on imaging geometry accuracy. Phantom reconstructions
      of known seed locations were used to show optimization of the imaging geometry
      for consistency with the observed datasets in multiple variable angle images can
      be used to obtain more accurate source and detector positions and reduce
      uncertainty in reconstructed seed positions. Furthermore, the most difficult part
      of backprojection methods is the matching of corresponding seeds between the
      variable angle images. With improved accuracy in imaging geometry, tighter
      constraints on possible seed matches can be used. This reduces the number of
      potential matches between images. Application to typical clinical data has shown
      a reduction in the number of possible matches. The benefits are observed when
      optimizations are performed on very small subsets of matched seeds, allowing a
      small number of obvious matches due to orientation or peripheral positioning to
      greatly simplify matching over the remainder of the implant.

PMID- 28512826
TI  - Poster - Thurs Eve-06: Maximizing eclipse IMRT dose accuracy by adjusting the
      dosimetric leaf gap parameter.
AB  - The dosimetric leaf gap (DLG) is a parameter used by Eclipse to model the rounded
      leaf ends of Varian MLCs. The DLGs were determined for the Millennium (M120) and
      High-Definition (HD120) model MLCs and taken as the difference between measured
      (0.6mm diode, IBA) and nominal MLC-defined profile FWHM values. Configuring the
      Eclipse pencil beam algorithm with the measured DLG gave poor agreement between
      measured and calculated IMRT dose distributions for the HD120 but not the M120.
      Agreement was optimized by adjusting the DLG for the HD120; 0.3mm changes in DLG
      were enough to cause significant variations in field dose agreement. Optimal DLG
      values of 0.04cm and 0.05cm were found for the 6MV HD120 and 10MV HD120,
      respectively, and 0.135cm 0.175cm for the 6MV M120 and 18MV M120, respectively.
      Agreement between measured and calculated dose distributions worsened for the AAA
      algorithm indicating separate DLG values may be required. A leaf calibration
      software upgrade also reduced agreement by changing the physical leaf position
      for a given location value. The change was detected using film and the picket
      fence MLC-pattern which places the two banks of opposing leaves at the same
      position but at different times. The DLG value can be adjusted from its measured
      physical value to improve the dosimetric accuracy of Eclipse IMRT plans and
      compensate for the effects of treatment planning algorithm and varying leaf
      calibrations. Since leaf calibrations are variable it is important to define the
      dosimetric leaf gap for each accelerator and clinic.

PMID- 28512827
TI  - Poster - Thurs Eve-17: Stand alone software for deforming delivered dose
      distributions to account for daily anatomical variations in prostate patients
      treated on the TomoTherapy Hi-Art II system.
AB  - The acquisition of daily megavoltage (MV)-CT images provides an invaluable tool
      in the delivery of adaptive radiotherapy (ART) on the TomoTherapy Hi-ART II
      system. Using TomoTherapy's Planned Adaptive software, delivery sinograms can be
      applied to pre-treatment MVCT images to generate daily delivered dose
      distributions, allowing for the potential comparison of planned and delivered
      doses. However, daily patient anatomical variations complicate the task and
      accurate comparison requires that daily doses be evaluated in the same references
      frame as the planned dose. Each anatomical point in daily MVCT images must be
      mapped to its corresponding point in the patient planning CT and that deformation
      map must be applied to the daily dose distribution. Stand alone software has been
      developed for the comparison of planned and delivered doses for TomoTherapy
      prostate patients. Software inputs are the planning CT, planning structure data,
      planned dose distribution, daily MVCT and delivered dose distribution. The
      software uses an in-house developed automatic voxel-based deformable registration
      algorithm designed and optimized specifically for the registration of prostate CT
      images to achieve anatomical correspondence between MVCT and planning images. The
      resultant deformation map is applied to the daily dose distribution and the
      software outputs the deformed daily dose distribution in the planning CT's
      reference frame, as well as a delivered DVH for each of the planning CT's ROI.
      The software allows for a number of potential research opportunities, in
      particular, the calculation of the cumulative dose delivered over the course of
      treatment for prostate patients treated on the Hi-Art II system.

PMID- 28512829
TI  - Sci-Thurs PM: Delivery-11: Image guidance for prostate IMRT using low dose cone
      beam CT.
AB  - Linac-mounted cone beam computed tomography (CBCT) using Varian's On Board Imager
      (OBI) currently delivers significant imaging dose and lacks automatic methods for
      clinical target volume (CTV) registration. In this work, we address these two
      issues to enable frequent treatment corrections during a course of prostate
      intensity modulated radiation therapy (IMRT). The process starts by acquiring a
      low dose (low mAs) CBCT image after patient setup. The image is then used in one
      of two automatic image guidance strategies. The "global" technique provides the
      couch corrections necessary to improve patient setup by registering the CBCT to
      the planning CT. The "local" method involves non-rigid registration of the
      planning CT to the CBCT followed by automatic treatment re-optimization using the
      deformed planning CT and contours. Thus, the global method attempts to correct
      patient setup to match the planned treatment, while the local method corrects the
      treatment to match the patient setup. Both techniques were evaluated using images
      of an anthropomorphic male pelvis phantom. Global image guidance resulted in a
      registration error of 3.6 +/- 1.3 mm (imaging dose independent) and high
      treatment doses to the bladder and rectum for large magnitude motion. The local
      technique always resulted in clinically acceptable treatment doses due to a
      reduced registration error of 2.3 +/- 0.8 mm, obtained at 15% of the OBI's
      default dose (125 kVp, 2 mAs per projection). These preliminary results show that
      our automatic local image guidance technique reduces imaging dose and is
      sufficiently accurate and robust for application in prostate IMRT.

PMID- 28512828
TI  - Poster - Thurs Eve-28: New brain diffusion analysis method: White matter grey
      matter dissasociation.
AB  - Diffusion MR studies are often used to investigate the physical properties of
      brain tissues (1, 2). It is known that a full characterisation of the diffusion
      decay for brain could give valuable information about the structural organisation
      of cerebral tissue. The significance of the present diffusion decay study lies in
      the combination of three novel procedures to provide a better characterization of
      the diffusion decay: i) the acquisition of a large number of b-values (96 b
      values up to 10,000 s/mm2 ), ii) the application of a noise correction technique
      (3) to the acquired data, and iii) the use of a Non Negative Least Squares (NNLS)
      fitting algorithm to evaluate the diffusion coefficients. The presence of noise
      in magnitude MR images can affect the calculation of the diffusion parameters (4)
      and therefore a noise correction technique (3) is applied. The NNLS algorithm is
      used to fit the corrected data instead of the more commonly used Levenberg
      Marquardt algorithm since the NNLS algorithm does not require the number of
      components to be specified, nor does it need initial estimates of the fitting
      parameters as input; thus giving it more versatility as a fitting tool for the
      diffusion decay. The results indicate that the diffusion decays in grey and white
      matter have one and two components, respectively. Consequently, the short
      diffusion component in white matter (Fig. 1.c) can be used as a tool in the
      disassociation of white and grey matter tissues.

PMID- 28512830
TI  - Poster - Thurs Eve-10: The accuracy of MU calculations for enhanced dynamic wedge
      with the Varian's anisotropic analytical algorithm.
AB  - The Anisotropic Analytical Algorithm (AAA) of the Varian Eclipse treatment
      planning system calculates absolute dose for a variety of beam settings including
      those with an enhanced dynamic wedge (EDW). This algorithm has gone through a
      number of version updates since it was first released in July 2005. Previous
      versions of AAA have come with instructions on how to manually modify the several
      parameters that affect the EDW output factors. The current version of AAA
      (8.1.17) has had the EDW module modified so that problems associated with the
      second-source parameter calculation are resolved. The purpose of this paper is to
      report on the observed discrepancies between measured and calculated EDW output
      factors for the current version (8.1.17) and the most recent version (8.0.05) of
      the AAA algorithm. EDW output factors were measured in a water-equivalent phantom
      on a Varian 2100iX LINAC running 6MV and 15MV photon beams. A similar geometry
      was modelled in the treatment planning system to calculate the number of monitor
      units required to deliver a specified dose at a depth with or without an EDW.
      Measurements and calculations were performed for a wide range of EDW wedge
      angles, field sizes and depths. The best EDW output factor results possible with
      version 8.0.05 yielded discrepancies up to 7% despite considerable parameter
      adjustment. The new version (8.1.17) gave results within 1% of measured without
      any parameter adjustment. Care should be taken when using any Eclipse AAA
      algorithm earlier than version 8.1.17 to calculate MUs for Varian enhanced
      dynamic wedge.

PMID- 28512831
TI  - Poster - Thurs Eve-01: Comparison of clinical IMRT plan quality and delivery
      accuracy: Few large segments vs many small segments.
AB  - Commercial radiation treatment planning systems for intensity modulation use
      optimization algorithms that can vary multi-leaf collimator (MLC) segment sizes,
      segment number and the minimum number of monitor units (MU) per segment. These
      parameters are varied according to the treatment site, size, location, and
      proximity to the organs at risk. This study compares the utility of optimization
      using (Case A) few large segments and a higher minimum MU per segment to that of
      (case B) using many smaller segments with a lower minimum MU per segment. For
      Case A, the patient benefits from a reduced treatment time associated with fewer
      MUs and fewer MLC movements and an increased accuracy in dose delivery. Also,
      shorter treatment times may lead to fewer patient movement uncertainties. The
      accumulated MLC leakage dose is reduced, the patient specific quality assurance
      (QA) is more manageable and small field modeling inaccuracies are reduced.
      Pinnacle-3 (v8) plans are generated with direct machine parameter optimization
      (DMPO) for both scenarios. Three dimensional dose distributions and dose volume
      histograms are used to compare plan quality. We compare plans using few large MLC
      segments with those using many small MLC segments for some clinical cases.
      Improved plan quality is demonstrated using fewer MLC segments. Dose QAs are
      performed and compared for each scenario using MapCheck and film. When comparing
      dose delivery accuracy between different MU per segment settings, a decrease in
      delivery errors with minimum MU size is observed. In conclusion, few large MLC
      segments with larger area should be used when possible.

PMID- 28512832
TI  - Poster - Thurs Eve-12: A needle-positioning robot co-registered with volumetric x
      ray micro-computed tomography images for minimally-invasive small-animal
      interventions.
AB  - Preclinical research protocols often require the delivery of biological
      substances to specific targets in small animal disease models. To target
      biologically relevant locations in mice accurately, the needle positioning error
      needs to be < 200 MUm. If targeting is inaccurate, experimental results can be
      inconclusive or misleading. We have developed a robotic manipulator that is
      capable of positioning a needle with a mean error < 100 MUm. An apparatus and
      method were developed for integrating the needle-positioning robot with
      volumetric micro-computed tomography image guidance for interventions in small
      animals. Accurate image-to-robot registration is critical for integration as it
      enables targets identified in the image to be mapped to physical coordinates
      inside the animal. Registration is accomplished by injecting barium sulphate into
      needle tracks as the robot withdraws the needle from target points in a tissue
      mimicking phantom. Registration accuracy is therefore affected by the positioning
      error of the robot and is assessed by measuring the point-to-line fiducial and
      target registration errors (FRE, TRE). Centroid points along cross-sectional
      slices of the track are determined using region growing segmentation followed by
      application of a center-of-mass algorithm. The centerline points are registered
      to needle trajectories in robot coordinates by applying an iterative closest
      point algorithm between points and lines. Implementing this procedure with four
      fiducial needle tracks produced a point-to-line FRE and TRE of 246 +/- 58 MUm and
      194 +/- 18 MUm, respectively. The proposed registration technique produced a TRE
      < 200 MUm, in the presence of robot positioning error, meeting design
      specification.

PMID- 28512833
TI  - Poster - Thurs Eve-23: Effect of lung density and geometry variation on
      inhomogeneity correction algorithms: A Monte Carlo dosimetry evaluation.
AB  - This study provides new information on the evaluation of the lung dose
      calculation algorithms as a function of the relative electron density of lung,
      rhoe,lung . Doses calculated using the collapsed cone convolution (CCC) and
      adaptive convolution (AC) algorithm in lung with the Pinnacle3 system were
      compared to those calculated using the Monte Carlo (MC) simulation (EGSnrc-based
      code). Three groups of lung phantoms, namely, "Slab", "Column" and "Cube" with
      different rhoe,lung (0.05-0.7), positions, volumes and shapes of lung in water
      were used. 6 and 18MV photon beams with 4*4 and 10*10cm2 field sizes produced by
      a Varian 21EX Linac were used in the MC dose calculations. Results show that the
      CCC algorithm agrees well with AC to within +/-1% for doses calculated in the
      lung phantoms, indicating that the AC, with 3-4 times less computing time
      required than CCC, is a good substitute for the CCC method. Comparing the CCC and
      AC with MC, dose deviations are found when rhoe,lung are ?0.1-0.3. The degree of
      deviation depends on the photon beam energy and field size, and is relatively
      large when high-energy photon beams with small field are used. For the penumbra
      widths (20%-80%), the CCC and AC agree well with MC for the "Slab" and "Cube"
      phantoms with the lung volumes at the central beam axis (CAX). However,
      deviations >2mm occur in the "Column" phantoms, with two lung volumes separated
      by a water column along the CAX, using the 18MV (4*4cm2 ) photon beams with
      rhoe,lung ?0.1.

PMID- 28512834
TI  - Sci-Thurs PM: Delivery-06: 2-D lag and response nonlinearity corrections for
      dynamic IMRT verification using an EPID.
AB  - In recent years, EPIDs have been used for pre-treatment IMRT verification.
      Although EPID lag and signal nonlinearities have been investigated, they have not
      been implemented in the verification process. In dynamic sliding-window IMRT
      delivery, the dose delivered, and the time between the end of dose delivery and
      the end of image acquisition differ between pixels. The resulting differences in
      lag and signal-response across the image can cause artificial asymmetries and
      amplitude changes in measured EPID dose images. These artifacts alter the
      agreement between measured and predicted images, potentially complicating the
      assessment of clinical IMRT verifications. A method of 2-D (pixel-by-pixel)
      correction was developed based on data from sets of experiments performed to
      independently quantify the lag and nonlinearity characteristics of Varian's aS500
      EPID. To test the correction, it was applied to two sweeping window 10*10 cm2
      fields that differ only in sweeping direction. The correction resolved
      discrepancies in the symmetry between these two cases, and the differences
      between measured and predicted amplitudes evident when small numbers of MUs were
      delivered. To illustrate its potential use, the correction technique was applied
      to a measured image of a clinical IMRT field that produced a relatively poor
      verification result. The correction partially accounted for discrepancies between
      measured and Eclipse-predicted images of this field, reducing the percentage of
      pixels failing a Gamma analysis (3 %, 3 mm) from 8.5 to 5.6 %. This correction
      technique can be used to help resolve the source of discrepancies in troublesome
      clinical IMRT verifications.

PMID- 28512835
TI  - Poster - Thurs Eve-34: Extended CT-range in RT planning of pelvic cancer
      treatment in presence of hip replacements.
AB  - Extended CT range in conventional CT scanners has a potential to allow for a more
      conformal treatment of patients with hip prosthesis. Its use may limit
      inaccuracies in electron density maps that are observed due to severe artifacts
      in CT data. In this study, we investigate the use of CT images with extended CT
      numbers in dose calculations and compare the results of calculations with
      standard CT data and measured doses. A phantom containing a hip prosthesis was
      scanned and treatment was planned with extended and standard CT numbers. The
      density override function was used to eliminate the effect of artifacts in the
      region outside of the metallic implant, while raw CT numbers were used to
      indicate density within the implant. Dose measurements were performed with two
      types of ion chambers at 6, 10 and 18MV energies. Our results indicate that data
      with extended CT range result in a better agreement between measured and
      calculated dose at the central position of the body phantom, as should be
      expected. However, CT artifacts within the implant region also result in
      discrepancies between the measured and calculated dose. The discrepancy is
      greater at lower cross-sectional thickness where bright, high density surface
      artifacts are high relative to the artificially low density inner region of the
      implant. Potential ways of resolving the discrepancies are outlined and a
      possibility of their application to clinical routine will be discussed.

PMID- 28512836
TI  - Poster - Thurs Eve-05: An assessment of PDDs and outputs predicted by a Monte
      Carlo-based treatment planning system for electron beams.
AB  - Monte Carlo simulation is currently considered to be the most accurate method of
      calculating dose distributions for electron beam therapy, and commercial
      treatment planning software using simplified macro Monte Carlo is available for
      electron treatment planning. In this work, Eclipse V8.1.18 is being investigated
      in preparation for the clinical use of CT-based electron treatment planning.
      Water tank measurements of percentage depth doses (PDDs) and absolute outputs at
      depth of maximum dose (Zmax ) under different geometric conditions are compared
      to the results calculated by Eclipse. The measurements are carried out for a
      range of electron energies (6, 9, 12, and 16 MeV) for the standard open field
      (10*10 cm2 ) and for circular cutouts (2, 3, and 6 cm diameters) at SSD of 100
      cm. In addition, extended SSDs (105 and 110 cm) and oblique beam incident (gantry
      345 degree) for the open field and 3 cm diameter cutout are measured and compared
      to Eclipse. For PDDs, the results predicted by Eclipse are generally acceptable,
      falling mostly within 5% of those measured in water. For output, the results
      predicted by Eclipse are similar, falling mostly within 3% of those measured in
      water. We observed the greatest differences between Eclipse and measurements near
      the water surface and in high dose gradients for PDDs. A similar observation is
      noted for a small field in the case of outputs.

PMID- 28512837
TI  - Poster - Thurs Eve-16: Just-in-time tomography (JiTT).
AB  - Soft-tissue target motion is one of the main concerns in high-precision radiation
      therapy. Cone beam computed tomography (CBCT) has been developed recently to
      image soft-tissue targets in the treatment room for image-guided radiation
      therapy. However, due to its relatively long image acquisition time the CBCT
      approach cannot provide images of the target at the instant of the treatment and
      thus is not adequate for imaging targets with intrafraction motion. In this work,
      a new concept for image-guided radiation therapy- just-in-time tomography (JiTT) 
      is introduced. Differing from CBCT, JiTT takes much less time to generate the
      needed tomographical, beam's-eye-view images of the treatment target at the right
      moment to guide the radiation therapy treatment. A system to achieve JiTT is
      proposed and its feasibility is investigated. Research supported by Siemens.

PMID- 28512838
TI  - Poster - Thurs Eve-27: Method of estimating imaging dose to patients from on-line
      cone-beam computed tomography using patient size data.
AB  - The use of on-line kilovoltage cone-beam computed tomography (CBCT) is increasing
      as part of the current evolution of image-guided radiotherapy. At our
      institution, we use Varian's On Board Imager(r) (OBI) mainly for imaging prostate
      cancer patients. Since daily CBCT can add significant dose, we have performed a
      comprehensive set of dose measurements using acrylic cylindrical phantoms using
      ionization chambers as well as skin dose measurements using Thermoluminescence
      Dosimeters (TLD). The TLD were calibrated under chosen reference conditions
      (10*10 cm2 field size at 100 cm SSD) using the OBI beam with bowtie filters (125
      kVp, 6.0 mm Al). For the patients, TLD were placed on the anterior, left and
      right lateral locations to give the peripheral dose. The CBCT dose values (in
      units of mGy/100mAs) were then used to model the central (phantom only) and
      peripheral dose (phantom and patients) as a function of equivalent diameter, deq
      , using exponential functions. Dose values measured in Rando phantom as well as
      published dose values agreed with the model quite well for deq ? 24 cm (body),
      but there was higher variation in CBCT dose for deq ? 18 cm (head). Hence, it is
      recommended that skin dose be measured for head scans to validate the estimate.
      This method provides a quick estimate of CBCT dose so that a decision can be made
      whether to incorporate it into the treatment prescription. Also, knowledge of
      CBCT dose as a function of patient size may enable reduction of the total mAs for
      smaller body scans.

PMID- 28512839
TI  - Sci-Thurs PM: Delivery-10: Marker trajectory reconstruction using cone-beam CT
      projection images.
AB  - Image guidance and daily verification is becoming increasingly important in
      radiotherapy today, especially when dealing with moving targets. Cone-beam CT
      (CBCT) is a 3D imaging modality available in the treatment room, but it is
      difficult to assess motion from this integrated image. If a fiducial marker is
      placed in a moving target, it can easily be identified in the raw projection
      images that are captured during the CBCT. Normally, this projection data is
      discarded after reconstruction, but we show a method that can be used to extract
      trajectory information from this data. A CBCT was acquired of a moveable phantom
      with a known motion and an implanted gold seed. During the scan, the phantom
      underwent 14 cycles of motion. The fiducial marker location was determined from
      each raw projection image, and the data was separated into individual breathing
      cycles. Each point in each cycle was then assigned a 'breath phase' based
      temporal position in the cycle. To reconstruct a single 3D position in room
      coordinates, two nearly orthogonal images at the same 'breath phase' but in two
      different breaths were used. Multiple reconstructions from 14 nearly orthogonal
      pairs produced points which on average should represent the 4D trajectory. When
      compared to the true motion, the reconstructed average trajectory had an accuracy
      of less than 1mm. We have shown that in the ideal case of identical motion in
      each cycle we can accurately measure the 4D trajectory. Future work will use this
      tool to collect and estimate the trajectories for more realistic motions which
      differ from cycle to cycle.

PMID- 28512840
TI  - Poster - Thurs Eve-38: CT Imaging in high dose rate brachytherapy for treatment
      of cervical cancer: Estimation of dose to bowel.
AB  - Treatment of cervical cancer often involves intracavitary high dose rate (HDR)
      brachytherapy. Dose delivered to the bladder and rectum are typically estimated
      using the ICRU reference points. Dose to the sigmoid and small bowel are not
      estimated, yet these organs typically exhibit significant complication rates. The
      objective of this study was to estimate dose to the small bowel and sigmoid using
      CT images. Bladder and rectum dose estimates obtained from the reference point
      method were also compared to those obtained from CT images. Eighteen CT scans
      taken before or after treatment of women treated with HDR using ring and tandem
      applicators were included in this study. The small bowel, sigmoid, bladder and
      rectum were contoured and the ICRU points were digitized. The minimum dose to 2cc
      (D2cc ) of each organ was calculated and normalized to % prescribed to Point A.
      Average D2cc bowel dose was 70%. D2cc bowel dose was significantly higher than
      both D2cc rectal (27%) and D2cc sigmoid (31%) doses. The average D2cc bladder and
      rectal doses were 68% (p=NS) and 27% (p<0.001) of prescribed Point A dose. D2cc
      bowel dose, although significantly higher than rectum and sigmoid, is within an
      acceptable limit. D2cc bladder and rectum values are either not significantly
      different from or are significantly lower than ICRU reference values. The results
      of this study suggest that CT imaging is not necessary for determination of dose
      to organs at risk. However, image guidance is of value for identifying
      perforations prior to commencing treatment.

PMID- 28512841
TI  - Poster - Thurs Eve-09: Evaluation of a commercial 2D ion-chamber array for
      intensity modulated radiation therapy dose measurements.
AB  - Experimental verification of calculated dose from a treatment planning system is
      often essential for quality assurance (QA) of intensity modulated radiation
      therapy (IMRT). Film dosimetry and single ion chamber measurements are commonly
      used for IMRT QA. Film dosimetry has very good spatial resolution, but is labor
      intensive and absolute dose is not reliable. Ion chamber measurements are still
      required for absolute dose after measurements using films. Dosimeters based on 2D
      detector arrays that can measure 2D dose in real-time are gaining wider use.
      These devices provide a much easier and reliable tool for IMRT QA. We report the
      evaluation of a commercial 2D ion chamber array, including its basic performance
      characteristics, such as linearity, reproducibility and uniformity of relative
      ion chamber sensitivities, and comparisons between measured 2D dose and
      calculated dose with a commercial treatment planning system. Our analysis shows
      this matrix has excellent linearity and reproducibility, but relative
      sensitivities are tilted such that the +Y region is over sensitive, while the -Y
      region is under sensitive. Despite this behavior, our results show good agreement
      between measured 2D dose profiles and Eclipse planned data for IMRT test plans
      and a few verification plans for clinical breast field-in-field plans. The gamma
      values (3% or 3 mm distance-to-agreement) are all less than 1 except for one or
      two pixels at the field edge This device provides a fast and reliable stand-alone
      dosimeter for IMRT QA.

PMID- 28512842
TI  - Poster - Thurs Eve-20: Analysis of dosimetric differences between dose-to-water
      vs. dose-to-medium calculations for electron beams.
AB  - PURPOSE: With the advent of commercial Monte Carlo based treatment planning
      systems (TPS) typically calculating dose-to-medium, Dm , as opposed to dose-to
      water, Dw , calculated by conventional TPS, a thorough analysis of differences
      between these treatments plans is required. Such an analysis has not yet been
      carried out. The purpose of our study was to evaluate dosimetric differences
      between such plans generated with a commercial MC based TPS. MATERIALS AND
      METHODS: The analysis included plans of 53 breast cancer patients treated with
      electron beams ranging from 6-20 MeV. These plans were originally calculated
      using the Dm approach. Keeping the original beam arrangements and the same
      calculation parameters, the plans were recalculated using the Dw approach. The
      comparison between Dm and Dw plans was performed by means of dose volume
      histograms and isodose distributions on the corresponding CT slices. RESULTS AND
      CONCLUSIONS: The plans calculated using Dm vs. Dw show some differences, with
      magnitudes depending on the location of the tumor and organs at risk and the beam
      energy. The largest difference was found for the treatment of the chest wall
      after complete mastectomy with 13 MeV beam. The dose to internal mammary nodes
      was 43.6 Gy and 39.0 Gy for Dm and Dw approach, respectively. This amounts to
      8.1% difference in the maximum dose delivered to that volume. For the same
      patient, the dose received by the right lung was 13.5 and 15.4 Gy for Dm and Dw
      approach, respectively, which amounts to 3.6% difference in dose delivered to
      this lung.

PMID- 28512843
TI  - Assessment of the efficacy and safety of a new complex skin cream in Asian women:
      A controlled clinical trial.
AB  - BACKGROUND: Medical products such as hydroquinone and tretinoin have been widely
      used to treat various types of skin hyperpigmentation. However, these products
      are limited in daily use given their adverse effects. Other alternative agents
      with fewer adverse side effects have been developed. However, single agents often
      do not produce satisfactory results. AIMS: To evaluate the efficacy and safety of
      a new brightening complex cream containing niacinamide, tranexamic acid,
      oxyresveratrol, glutathione disulfide, and linoleic acid. PATIENTS AND METHODS: A
      total of 26 Korean women seeking to lighten their skin were enrolled. The product
      was applied on the face two times per day for 12 weeks. Standardized photographs
      were taken at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was assessed
      using melanin index (MI), erythema index (EI), and chromatic aberration values
      (L*, a*, and b*). Improvement perceived by investigators and patients was
      measured as well. RESULTS: The L*-value was increased at 8 weeks (0.7+/-2.5,
      P<.05) and at 12 weeks (0.8+/-2.5, P<.05). The MI was significantly decreased at
      8 weeks (-4.2+/-4.5, P<.05) and at 12 weeks (-3.8+/-4.8, P<.001). The EI was
      significantly improved at 12 weeks (-3.2+/-2.2, P<.001). More than 80% of
      patients were considered improved at 12 weeks based on the view of the
      investigators and patients. CONCLUSIONS: The new brightening complex cream was
      proved to be effective and safe in Asian women.

PMID- 28512845
TI  - Work, retirement, and muscle strength loss in old age.
AB  - Reduced muscle strength is an accurate predictor of functional limitations,
      disability, and mortality. Hence, understanding which socio-economic factors
      contribute to preserve muscle strength in old age is central to the design of
      social policies that help reducing these health risks. Using data on handgrip
      strength collected by the Survey of Health, Ageing and Retirement in Europe for
      the population of Europeans aged 50+ and the exogenous variation in pension
      eligibility age across countries over time, we estimate that the retirement
      transition has a short-term positive causal effect on muscle strength. However,
      this protective effect is not persistent, as retirement speeds up the age-related
      trend in muscle strength loss, especially for blue-collar workers and males. The
      "holy grail" of early retirement may not be such a good deal for retirees'
      longevity and physical functioning late in life.

PMID- 28512846
TI  - Melatonin influences the sonic hedgehog signaling pathway in porcine cumulus
      oocyte complexes.
AB  - Melatonin, which is synthesized in the pineal gland and peripheral reproductive
      organs, has antioxidant properties and regulates physiological processes. It is
      well known that melatonin affects in vitro maturation (IVM) of oocytes and
      embryonic development in many species. However, beneficial effects of melatonin
      on IVM have been explained mainly by indirect antioxidant effects and little
      information is available on the underlying mechanism by which melatonin directly
      acts on porcine cumulus oocyte complexes (COCs). Sonic hedgehog (Shh) signaling
      is important for follicle development, oocyte maturation, and embryo development,
      and there may be a relationship between melatonin and Shh signaling. To examine
      this, we designed three groups: (i) control, (ii) melatonin (10-9  mol/L), and
      (iii) melatonin with cyclopamine (2 MUmol/L; Shh signaling inhibitor). The aim of
      this study was to investigate the effects of these agents on cumulus expansion,
      oocyte maturation, embryo development after parthenogenetic activation (PA), gene
      expression in cumulus cells, oocytes and blastocysts, and protein expression in
      COCs. Melatonin significantly increased the proportion of COCs exhibiting
      complete cumulus expansion (degree 4), PA blastocyst formation rates, and total
      cell numbers, which were inhibited by addition of cyclopamine. Simultaneously,
      the expression of cumulus expansion-related genes (Ptgs1, Ptgs2, and Has2) and
      Shh signaling-related genes (Shh, Pthc1, Smo, and Gli1) and proteins (Ptch1, Smo,
      and Gli1) in cumulus cells was upregulated in the melatonin-treated group, and
      these effects were also inhibited by cyclopamine. In conclusion, our results
      suggest that Shh signaling mediates effects of melatonin to improve porcine
      cumulus expansion and subsequent embryo development.

PMID- 28512848
TI  - Bullous fixed drug eruption due to fluconazole, imitating herpes simplex.

PMID- 28512849
TI  - Synthesis and luminescence properties of brick-shaped lanthanum-organic
      frameworks with mesoporous and macroporous architectures.
AB  - Generally, metal-organic frameworks (MOFs) are made up from kinds of repeating
      microporous structure. Here, a series of Eu3+ ions activated terephthalate-based
      lanthanum-organic frameworks (La-MOFs) was synthesized by a hydrothermal
      reaction. By controlling the reaction time, we obtained some unique brick-shaped
      La-MOFs in a micron scale size range, and these La-MOFs showed tunable mesoporous
      and macroporous architectures. It is speculated that the change in the
      composition and structure of building units results in the formation of this
      mesoporous and macroporous heterogeneous architectures. Powder X-ray diffraction
      patterns and Eu3+ luminescence behavior support the speculation.

PMID- 28512851
TI  - Rebuttal to Dr Bianchi Commentary.

PMID- 28512850
TI  - In situ handheld three-dimensional bioprinting for cartilage regeneration.
AB  - Articular cartilage injuries experienced at an early age can lead to the
      development of osteoarthritis later in life. In situ three-dimensional (3D)
      printing is an exciting and innovative biofabrication technology that enables the
      surgeon to deliver tissue-engineering techniques at the time and location of
      need. We have created a hand-held 3D printing device (biopen) that allows the
      simultaneous coaxial extrusion of bioscaffold and cultured cells directly into
      the cartilage defect in vivo in a single-session surgery. This pilot study
      assessed the ability of the biopen to repair a full-thickness chondral defect and
      the early outcomes in cartilage regeneration, and compared these results with
      other treatments in a large animal model. A standardized critical-sized full
      thickness chondral defect was created in the weight-bearing surface of the
      lateral and medial condyles of both femurs of six sheep. Each defect was treated
      with one of the following treatments: (i) hand-held in situ 3D printed
      bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed
      bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated
      (control, C group). At 8 weeks after surgery, macroscopic, microscopic and
      biomechanical tests were performed. Surgical 3D bioprinting was performed in all
      animals without any intra- or postoperative complication. The HH biopen allowed
      early cartilage regeneration. The results of this study show that real-time, in
      vivo bioprinting with cells and scaffold is a feasible means of delivering a
      regenerative medicine strategy in a large animal model to regenerate articular
      cartilage.

PMID- 28512852
TI  - Sleep in mental disorders, ageing and memory, insomnia, external factors on sleep
      and basic research.

PMID- 28512853
TI  - Derivation and validation of the APPEND score: an acute appendicitis clinical
      prediction rule.
AB  - BACKGROUND: Although many clinical prediction rules (CPRs) for appendicitis
      exist, none have been developed for a New Zealand population presenting with
      right iliac fossa (RIF) pain. The aim of this study was to derive and validate an
      appendicitis CPR for our population. METHOD: This is a retrospective review of
      all patients from December 2010 to February 2012 of at least 15 years of age
      presenting to the general surgery service with RIF pain. Patient data were
      divided into derivation and validation groups. Univariate and multiple regression
      analyses identified significant predictors of appendicitis which were used to
      construct a CPR. A retrospective validation study was then performed and the CPR
      was refined accordingly. Finally, the accuracy of the CPR was tested. RESULTS:
      The final components of the new CPR, the APPEND score, were Anorexia, migratory
      Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender
      (Dude). This CPR has an area under the receiver operating characteristic curve of
      0.84. The CPR can stratify patients into low, intermediate and high-risk groups
      which may standardize patient care and reduce the negative appendicectomy rate.
      CONCLUSION: A new CPR for predicting appendicitis, in patients presenting with
      RIF pain, has been derived and validated for use in our population. A prospective
      study to further evaluate its performance is required.

PMID- 28512854
TI  - Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly Through
      Regulation of the TLR4/MAPK/NF-kappaB Axis via AMPK Activation.
AB  - Acute lung injury (ALI) often leads to high mortality, and there is as yet no
      effective drug treatment. The present study aimed to investigate protective
      effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia
      grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1,
      10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal
      administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose
      dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1beta, IL
      6, TNF-alpha and HMGB1) release and higher MPO activity in lung tissues induced
      by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not
      only increased the phosphorylation of adenosine 5'-monophosphate-activated
      protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4
      (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also
      inhibited the activation of MAPKs and nuclear factor kappaB (NF-kappaB)
      signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory
      effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a
      pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of
      MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial
      role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down
      regulating TLR4/MAPK/NF-kappaB signalling pathways. Copyright (c) 2017 John Wiley
      & Sons, Ltd.

PMID- 28512855
TI  - Insulin-like growth factor I enhances the developmental competence of yak embryos
      by modulating aquaporin 3.
AB  - The objective of our present study was to determine the effects of insulin-like
      growth factor I (IGF-I) on the development of yak (Bos grunniens) embryos after
      cumulus-oocyte complex (COC) vitrification and warming followed by in vitro
      fertilization (IVF). In Experiment 1, the yak COCs underwent vitrification and
      then IVF. Embryos were incubated in synthetic oviductal fluid (SOF) supplemented
      with four concentrations (0, 50, 100 and 200 ng/ml) of IGF-I, while the yak COCs
      without vitrification or IGF-I supplementation acted as the control group; the
      BAX, BCL-2, AQP3mRNA and aquaporin 3 (AQP3) protein expression levels in the five
      groups of blastocysts were evaluated using quantitative real-time PCR and
      immunofluorescence analyses. In Experiment 2, the groups described above were
      fertilized and incubated. The cleavage rate, blastocyst rate, total cell count
      per blastocyst and the rate of growth of the inner cell mass (ICM) and
      trophectoderm (TE) were evaluated. The results were as follows: (1) the AQP3 gene
      expression and protein expression in the control and 100 ng/ml IGF-I treatment
      groups were the highest. (2) The BAX gene expression was the lowest and the BCL-2
      gene expression was the highest in the control and 100 ng/ml IGF-I treatment
      groups. (3) The rates of cleavage and blastocysts in the control and 100 ng/ml
      IGF-I groups were higher than those in the other three groups. The total cell
      count per blastocyst in the vitrified and warmed 100 ng/ml IGF-I group (106.7 +/-
      4.9) and the control group (107.3 +/- 4.2) was higher than that in the vitrified
      and warmed 0 ng/ml IGF-I (91.2 +/- 3.1), 50 ng/ml IGF-I (92.3 +/- 3.7) and 200
      ng/ml IGF-I (92.4 +/- 3.7) groups. Therefore, we conclude that IGF-I can improve
      yak blastocyst developmental ability, cytomembrane permeability and formation of
      the blastocyst cavity after COC vitrification by improving the BAX, BCL-2 and
      AQP3 expression levels.

PMID- 28512856
TI  - Early-onset urticaria: a marker of cryopyrin-associated periodic syndrome.

PMID- 28512857
TI  - Interest of variations in microRNA-152 and -122 in a series of hepatocellular
      carcinomas related to hepatitis C virus infection.
AB  - AIM: Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C
      virus (HCV) infection and constitutes the main burden of this disease. The
      molecular mechanisms underlying the development of HCC are multiple and might
      involve certain microRNA (miR). As discordant results have been reported
      concerning the detection of expression of miR-152 and miR-122 in HCC, our aim was
      to measure the levels of both miRs in serum and liver samples. METHODS: We
      analyzed miR-152 and miR-122 expression by reverse transcription-quantitative
      polymerase chain reaction in a serum cohort from 14 HCV-infected patients who
      developed HCC, 20 HCV+ patients without HCC, and 19 control patients. We also
      studied miR-152 and miR-122 in an independent tissue cohort from 11 normal
      livers, and from paired HCC and non-tumor adjacent livers of 11 HCV-infected
      patients and 12 non-infected patients. RESULTS: In serum samples, higher levels
      of miR-122 were found in non-HCC HCV+ compared to HCC HCV+ and control groups,
      whereas miR-152 was detectable in a lower range in HCC HCV+ compared to non-HCC
      HCV+ and control groups. We found higher signals for miR-122 and miR-152 in non
      tumor liver and HCC tissues compared to control tissues. Hepatocellular carcinoma
      etiology had no detectable influence on miR-122 expression, whereas miR-152 was
      increased in HCV+ tissue samples. CONCLUSIONS: Detection of low values of
      circulating miR-152 is a potentially interesting marker of hepatocarcinogenesis
      in HCV+ patients, in contrast to miR-122, which varies according to hepatocyte
      damage.

PMID- 28512858
TI  - Comprehension of handwriting development: Pen-grip kinetics in handwriting tasks
      and its relation to fine motor skills among school-age children.
AB  - BACKGROUND/AIM: Numerous tools have been developed to evaluate handwriting
      performances by analysing written products. However, few studies have directly
      investigated kinetic performances of digits when holding a pen. This study thus
      attempts to investigate pen-grip kinetics during writing tasks of school-age
      children and explore the relationship between the kinetic factors and fine motor
      skills. METHODS: This study recruited 181 children aged from 5 to 12 years old
      and investigated the effects of age on handwriting kinetics and the relationship
      between these and fine motor skills. The forces applied from the digits and pen
      tip were measured during writing tasks via a force acquisition pen, and the
      children's fine motor performances were also evaluated. RESULTS: The results
      indicate that peak force and average force might not be direct indicators of
      handwriting performance for normally developing children at this age. Younger
      children showed larger force variation and lower adjustment frequency during
      writing, which might indicate they had poorer force control than the older
      children. Force control when handling a pen is significantly correlated with fine
      motor performance, especially in relation to the manual dexterity.
      CONCLUSIONS/SIGNIFICANCE OF THE STUDY: A novel system is proposed for analysing
      school-age children's force control while handwriting. We observed the
      development of force control in relation to pen grip among the children with
      different ages in this study. The findings suggested that manipulation skill may
      be crucial when children are establishing their handwriting capabilities.

PMID- 28512859
TI  - Exploring daily affective changes in university students with a mindful positive
      reappraisal intervention: A daily diary randomized controlled trial.
AB  - Brief and cost-effective interventions focused on emotion regulation techniques
      can buffer against stress and foster positive functioning. Mindfulness and
      positive reappraisal are two techniques that can mutually enhance one another to
      promote well-being. However, research testing the effectiveness of interventions
      combining mindfulness and reappraisal is lacking. The current pilot examined the
      effect of a combined mindful-reappraisal intervention on daily affect in a 5-day
      diary study with 106 university students. Participants were randomized to a
      mindful-reappraisal intervention (n = 36), a reappraisal-only intervention (n =
      34), or an active control activity (n = 36). All participants described a
      negative event each day but only reappraised the event in the intervention
      conditions. Using multilevel growth modelling, results indicated that negative
      affect in both interventions declined over 5 days compared to the control;
      however, there were no differences in the growth of positive affect. Compared to
      reappraisal-only, the mindful-reappraisal group reported overall lower daily
      negative affect and marginally higher daily positive affect over the 5-day
      intervention. These findings suggest that brief daily practice combining
      mindfulness and positive reappraisal can be trained as a self-regulatory resource
      to promote positive affect and buffer negative affect above and beyond
      reappraisal practice alone.

PMID- 28512860
TI  - Intrinsic cellular and molecular properties of in vivo hippocampal synaptic
      plasticity are altered in the absence of key synaptic matrix molecules.
AB  - Hippocampal synaptic plasticity comprises a key cellular mechanism for
      information storage. In the hippocampus, both long-term potentiation (LTP) and
      long-term depression (LTD) are triggered by synaptic Ca2+ -elevations that are
      typically mediated by the opening of voltage-gated cation channels, such as N
      methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity
      of the post-synaptic density is ensured by the extracellular matrix (ECM). Here,
      we explored whether synaptic plasticity is affected in adult behaving mice that
      lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO). We
      observed that the profiles of synaptic potentiation and depression in the dentate
      gyrus (DG) were profoundly altered compared to plasticity profiles in wild-type
      littermates (WT). Specifically, synaptic depression was amplified in a frequency
      dependent manner and although late-LTP (>24 hr) was expressed following strong
      afferent tetanization, the early component of LTP (<75 min post-tetanization) was
      absent. LTP (>4 hr) elicited by weaker tetanization was equivalent in WT and KO
      animals. Furthermore, this latter form of LTP was NMDAR-dependent in WT but not
      KO mice. Scrutiny of DG receptor expression revealed significantly lower levels
      of both the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor, of
      the metabotropic glutamate receptor, mGlu5 and of the L-type calcium channel, Cav
      1.3 in KO compared to WT animals. Homer 1a and of the P/Q-type calcium channel,
      Cav 1.2 were unchanged in KO mice. Taken together, findings suggest that in mice
      that lack multiple ECM proteins, synaptic plasticity is intact, but is
      fundamentally different.

PMID- 28512861
TI  - Rapid diagnosis of sepsis with TaqMan-Based multiplex real-time PCR.
AB  - BACKGROUND: The survival rate of septic patients mainly depends on a rapid and
      reliable diagnosis. A rapid, broad range, specific and sensitive quantitative
      diagnostic test is the urgent need. Thus, we developed a TaqMan-Based Multiplex
      real-time PCR assays to identify bloodstream pathogens within a few hours.
      METHODS: Primers and TaqMan probes were designed to be complementary to conserved
      regions in the 16S rDNA gene of different kinds of bacteria. To evaluate
      accurately, sensitively, and specifically, the known bacteria samples (Standard
      strains, whole blood samples) are determined by TaqMan-Based Multiplex real-time
      PCR. In addition, 30 blood samples taken from patients with clinical symptoms of
      sepsis were tested by TaqMan-Based Multiplex real-time PCR and blood culture.
      RESULTS: The mean frequency of positive for Multiplex real-time PCR was 96% at a
      concentration of 100 CFU/mL, and it was 100% at a concentration greater than 1000
      CFU/mL. All the known blood samples and Standard strains were detected positively
      by TaqMan-Based Multiplex PCR, no PCR products were detected when DNAs from other
      bacterium were used in the multiplex assay. Among the 30 patients with clinical
      symptoms of sepsis, 18 patients were confirmed positive by Multiplex real-time
      PCR and seven patients were confirmed positive by blood culture. CONCLUSION:
      TaqMan-Based Multiplex real-time PCR assay with highly sensitivity, specificity
      and broad detection range, is a rapid and accurate method in the detection of
      bacterial pathogens of sepsis and should have a promising usage in the diagnosis
      of sepsis.

PMID- 28512862
TI  - Group-based parent training programmes for improving emotional and behavioural
      adjustment in children.

PMID- 28512864
TI  - Fish kairomones induce spine elongation and reduce predation in marine crab
      larvae.
AB  - Specialized defense strategies are induced in zooplankton upon detection of
      predator chemical cues or kairomones. These defenses are well-described for
      freshwater zooplankters, with morphological defenses being particularly striking,
      but few studies have reported kairomone-induced morphological defenses in marine
      zooplankton. Here, we compare morphological responses to kairomones in the larvae
      of two marine crab species, estuarine mud crabs (Rhithropanopeus harrisii) and
      Asian shore crabs (Hemigrapsus sanguineus). When reared in the presence of fish
      kairomones, spine length increased by 2-3% in larval R. harrisii, while no
      morphological changes were identified in H. sanguineus. In subsequent feeding
      assays with a co-occurring fish predator (Atlantic silversides, Menidia menidia),
      consumption of R. harrisii was lower on larvae that had been reared with
      kairomones. In addition, we found that broods with smaller larvae are more likely
      to exhibit increases in spine length after kairomone exposure. Hence, the
      observed morphological response is likely influenced by larval size.

PMID- 28512863
TI  - Defining a multimodal signature of remote sports concussions.
AB  - Sports-related concussions lead to persistent anomalies of the brain structure
      and function that interact with the effects of normal ageing. Although post
      mortem investigations have proposed a bio-signature of remote concussions, there
      is still no clear in vivo signature. In the current study, we characterized white
      matter integrity in retired athletes with a history of remote concussions by
      conducting a full-brain, diffusion-based connectivity analysis. Next, we combined
      MRI diffusion markers with MR spectroscopic, MRI volumetric, neurobehavioral and
      genetic markers to identify a multidimensional in vivo signature of remote
      concussions. Machine learning classifiers trained to detect remote concussions
      using this signature achieved detection accuracies up to 90% (sensitivity: 93%,
      specificity: 87%). These automated classifiers identified white matter integrity
      as the hallmark of remote concussions and could provide, following further
      validation, a preliminary unbiased detection tool to help medical and legal
      experts rule out concussion history in patients presenting or complaining about
      late-life abnormal cognitive decline.

PMID- 28512866
TI  - Medial sural artery perforator free flap for the reconstruction of leg, foot and
      ankle defect: an excellent option.
AB  - BACKGROUND: The defects over the leg, foot and ankle are best covered with a thin
      pliable flap. The use of muscle flap for the reconstruction of these defects
      leaves a grafted, aesthetically inferior result. The medial sural artery
      perforator (MSAP) free flap gives a thin pliable tissue for the reconstruction
      with better aesthesis. METHODS: The study design was retrospective case analysis
      over a period of 2 years. All the patients who underwent flap for leg, foot and
      ankle defect reconstruction in the form of MSAP free flap were included in the
      study. The flap characteristics and aesthesis were assessed along with the
      patient satisfaction. The flap complication and donor site morbidity were also
      analysed. RESULTS: A total of seven MSAP free flaps were done for leg, foot and
      ankle reconstruction. The mean flap size was 14.29 * 6.6 cm and mean pedicle
      length was 9.71 cm. One flap had venous congestion post-operatively resulting in
      marginal flap loss. All the flaps had acceptable aesthesis with good patient
      satisfaction. There was donor site morbidity in two patients, in the form of
      wound dehiscence. CONCLUSION: MSAP free flap is a reliable choice for leg, foot
      and ankle defect reconstruction.

PMID- 28512865
TI  - Efficacy and safety of ruxolitinib in intermediate-1 IPSS risk myelofibrosis
      patients: Results from an independent study.
AB  - Patients with myelofibrosis at intermediate-1 risk according to the International
      Prognostic Score System are projected to a relatively long survival; nonetheless,
      they may carry significant splenomegaly and/or systemic constitutional symptoms
      that hamper quality of life and require treatment. Since registrative COMFORT
      studies included only patients at intermediate-2/high International Prognostic
      Score System risk, safety and efficacy data in intermediate-1 patients are
      limited. We report on 70 intermediate-1 patients treated with ruxolitinib
      according to standard clinical practice that were evaluated for response using
      the 2013 IWG-MRT criteria. At 6 months, rates of spleen and symptoms response
      were 54.7% and 80% in 64 and 65 evaluable patients, respectively. At 3 months,
      ruxolitinib-induced grade 3 anemia and thrombocytopenia occurred in 40.6% and
      2.9% of evaluable patients, respectively. Notably, 11 (15.9%) patients
      experienced at least one infectious event >=grade 2. Most (82.6%) patients were
      still on therapy after a median follow-up of 27 months. These data support the
      need for standardized guidelines that may guide the decision to initiate
      ruxolitinib therapy in this risk category, balancing benefit expectations and
      potential adverse effects.

PMID- 28512868
TI  - Metastasis-associated microRNA expression in canine uveal melanoma.
AB  - BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumour in
      dogs. There is no effective means of predicting whether a tumour will
      metastasize. microRNA (miRNA) metastasis signatures have been identified for
      several human cancers, including UM. AIMS: In this study we investigated whether
      metastasizing and non-metastasizing canine UMs can be distinguished by miRNA
      expression levels. MATERIALS AND METHODS: miRNA microarray profiling was used to
      compare miRNA expression in 8 metastasizing and 12 non-metastasizing formalin
      fixed, paraffin-embedded (FFPE) primary UM biopsies. RESULTS: Fourteen miRNAs
      exhibited statistically significant differences in expression between the
      metastasizing and non-metastasizing tumours. Class prediction analysis pinpointed
      9 miRNAs which categorized tumours as metastasizing or non-metastasizing with an
      accuracy of 89%. Of the discriminating miRNAs, 8 were up-regulated in
      metastasizing UM, and included 3 miRNAs implicated as potential "metastasis
      activators" in human cutaneous melanoma. The expression of 4 of the miRNAs was
      subsequently measured using the quantitative reverse transcription polymerase
      chain reaction (RT-qPCR), and their up-regulation in metastasizing tumours
      validated. CONCLUSION: miRNA expression profiles may potentially be used to
      identify UMs that will metastasize, and miRNAs that are up-regulated in
      metastasizing tumours may be targets for therapeutic intervention.

PMID- 28512867
TI  - The structural basis for inhibition of the classical and lectin complement
      pathways by S. aureus extracellular adherence protein.
AB  - The extracellular adherence protein (Eap) plays a crucial role in pathogenesis
      and survival of Staphylococcus aureus by inhibiting the classical and lectin
      pathways of complement. We have previously shown that Eap binds with nanomolar
      affinity to complement C4b and disrupts the initial interaction between C4b and
      C2, thereby inhibiting formation of the classical and lectin pathway C3 pro
      convertase. Although an underlying mechanism has been identified, the structural
      basis for Eap binding to C4b is poorly understood. Here, we show that Eap domains
      3 and 4 each contain a low-affinity, but saturable binding site for C4b. Taking
      advantage of the high lysine content of Eap, we used a zero-length crosslinking
      approach to map the Eap binding site to both the alpha'- and gamma-chains of C4b.
      We also probed the C4b/Eap interface through a chemical footprinting approach
      involving lysine modification, proteolytic digestion, and mass spectrometry. This
      identified seven lysines in Eap that undergo changes in solvent exposure upon C4b
      binding. We found that simultaneous mutation of these lysines to either alanine
      or glutamate diminished C4b binding and complement inhibition by Eap. Together,
      our results provide insight into Eap recognition of C4b, and suggest that the
      repeating domains that comprise Eap are capable of multiple ligand-binding modes.

PMID- 28512870
TI  - School-based physical activity programs for promoting physical activity and
      fitness in children and adolescents aged 6 to 18.

PMID- 28512869
TI  - Patterns of head and neck sarcoma in Australia.
AB  - BACKGROUND: Sarcomas affecting the head and neck often require complex management
      due to the combination of anatomic, aesthetic and oncological considerations. The
      incidence and patterns of presentation are poorly understood and have not been
      reviewed in the Australian population. METHOD: This study sourced incidence and
      demographic data from the National Cancer Registry at the Australian Institute of
      Health and Welfare for the years 1982-2009 (corresponding to 97.3% of the
      Australian population). All cases of sarcoma, according to ICD-O-3 classification
      ((International Classification of Diseases for Oncology, 3rd edition), were
      assessed. RESULTS: A total of 3911 new cases of sarcoma affecting the head and
      neck were recorded during the period 1982-2009, including 1383, 2106 and 442
      cases arising from skin, soft tissue and bone, respectively. The annual incidence
      rate of sarcomas affecting the head and neck was 1.59 per 100 000 population. The
      incidence of head and neck sarcoma rose substantially in older age groups (age 65
      years and above) and was most common in male patients (69%). Malignant fibrous
      histiocytoma (MFH) was the most common pathology. There was an increase in
      incidence in skin-origin sarcoma in the head and neck, particularly affecting
      elderly males. CONCLUSION: The incidence of head and neck sarcoma in Australia is
      higher than that reported for an equivalent European population. The increase in
      MFH arising from the skin in elderly male patients mirrors the patterns of common
      cutaneous malignancy, particularly melanoma, suggesting that ultraviolet
      radiation is an epidemiological factor. Management of head and neck sarcoma is
      complex and best managed in a specialist multidisciplinary environment.

PMID- 28512871
TI  - Sci-Fri PM: Planning-08: Zero diffusion radiochromic genipin-gelatin dosimeter.
AB  - PURPOSE: To develop a zero diffusion radiochromic hydrogel by cross-linking
      gelatin polymers with genipin, for three-dimensional (3-D) radiation dosimetry.
      METHOD AND MATERIALS: Gelatin and genipin were dissolved in distilled water and
      continuously stirred at 40C for thee hours and then sulfuric acid was acid prior
      to placing gel in containers. Concentrations of genipin, gelatin and sulfuric
      acid were varied to determine the optimal gel sensitivity for optical computed
      tomography (CT). Photon beams (4 MV x-rays, 1*1, 2*2, 3*3 cm) irradiated a 10 cm
      diameter cylinder of gel. Using a cone beam optical CT scanner at lambda = 590
      nm, zero diffusion was observed by recording sequential 3D scans separated by 18
      hours. Additional evidence was provided by sequential transmission photographs of
      a cuvette containing a sample that had been exposed to a 0.8 mm diameter, 1 mW,
      594 nm, He-Ne laser beam and photobleached. RESULTS: Radiochromic bleaching is a
      fast process, complete within seconds of termination of irradiation. Dose
      sensitivity increases with cross- linking density and sulfuric acid
      concentration. The initial optical density limits dose sensitivity, requiring
      approximately 30 Gy for 10 cm diameter samples to have reasonable contrast. More
      sensitive but darker gels require smaller samples. A comparison of profiles
      through 3D reconstructed dose distribution showed identical profiles for a time
      interval of 18 hours. Visually the sample maintained this image for six months
      when stored at 4C in a dark refrigerator. Transmission photographs of the laser
      beam image recorded by photobleaching remained constant when stored a 23 C in the
      dark for ten months. CONCLUSION: Radiochromic genipin gelatin gels form a
      permanent and stable image when protected from bright visible light. This result
      is a new, non-toxic material for 3D dosimetry.

PMID- 28512872
TI  - Sci-Sat AM(1): Imaging-07: Open field normalization: How to avoid inflation to
      MTF and DQE values caused by zero-frequency normalization.
AB  - PURPOSE: To show that the novel open-field normalization technique prevents a
      common error in calculation of the detective quantum efficiency (DQE) caused by
      zero-frequency normalization of the modulation transfer function (MTF). METHOD
      AND MATERIALS: Models describing zero-frequency and open-field normalization were
      used to derive the resulting measured MTF, noise power spectrum (NPS) and DQE
      using a finite region of interest (ROI) of image data. Simulated one-dimensional
      images containing Gaussian blur were used to model a deterministic system and to
      calculate the resultant values. Measurements were made using both zero-frequency
      and open-field normalization with ROIs ranging in size from 1-10 cm. RESULTS: Use
      of a finite ROI results in truncation of the system line-spread function (LSF)
      causing the zero-frequency value of the measured MTF to be less than the true MTF
      value of unity, and causes spectral leakage in both the MTF and NPS. Zero
      frequency normalization of the MTF inflates values at all non-zero frequencies.
      Since no zero-frequency normalization is performed on the NPS, this causes
      inflated DQE values. Simulated results show a 6% inflation of DQE values for a
      ROI of 10 cm, which increases as the ROI is reduced. Open-field normalization
      accurately determines MTF and NPS (and thus DQE) values at all frequencies away
      from zero frequency. CONCLUSION: Open-field normalization measurements provide a
      good estimate of the true MTF and DQE. This approach should be used to avoid a
      common error in DQE calculations that is not obvious and inflates DQE
      calculations by 5-20%.

PMID- 28512873
TI  - Poster - Thurs Eve-43: Verification of dose calculation with tissue inhomogeneity
      using MapCHECK.
AB  - MapCHECK (Sun Nuclear, Melbourne, FL) with 445 diode detectors has been used
      widely for routine IMRT quality assurance (QA)1 . However, routine IMRT QA has
      not included the verification of inhomogeneity effects. The objective of this
      study is to use MapCHECK and a phantom to verify dose calculation and IMRT
      delivery with tissue inhomogeneity. A phantom with tissue inhomogeneities was
      placed on top of MapCHECK to measure the planar dose for an anterior beam with
      photon energy 6 MV or 18 MV. The phantom was composed of a 3.5 cm thick block of
      lung equivalent material and solid water arranged side by side with a 0.5 cm slab
      of solid water on the top of the phantom. The phantom setup including MapCHECK
      was CT scanned and imported into Pinnacle 8.0d for dose calculation. Absolute
      dose distributions were compared with gamma criteria 3% for dose difference and 3
      mm for distance-to-agreement. The results are in good agreement between the
      measured and calculated planar dose with 88% pass rate based on the gamma
      analysis. The major dose difference was at the lung-water interface. Further
      investigation will be performed on a custom designed inhomogeneity phantom with
      inserts of varying densities and effective depth to create various dose gradients
      at the interface for dose calculation and delivery verification. In conclusion, a
      phantom with tissue inhomogeneities can be used with MapCHECK for verification of
      dose calculation and delivery with tissue inhomogeneity.

PMID- 28512874
TI  - Sci-Fri PM: Planning-01: Measured electron and x-ray angular distribution data
      for benchmarking Monte Carlo codes.
AB  - Monte Carlo (MC) studies of the output of medical linear accelerators have
      demonstrated that in-air profiles are useful in the beam commissioning process. A
      recent investigation of x-ray profiles (Tonkopi et al, Med. Phys 32 (9), 2005)
      showed very good agreement between measurement and EGSnrc calculations but to
      achieve this level of agreement the beam linac spot size, energy and angular
      divergence had to be treated as variables. In this project we carried out
      measurements and MC calculations for an electron accelerator for which the
      initial beam parameters are well known. Two sets of investigations were carried
      out. In the first we measured electron scatter distributions for a range of
      scattering foils and electron energies of 13 and 20 MeV. The profiles were
      parameterised and compared to EGSnrc Monte Carlo calculations. It was found that
      generally the EGSnrc calculations gave agreement with the measurements within 1.5
      %. In the second investigation, which is on-going, in-air profiles were obtained
      for photon beams produced using different targets (from beryllium to lead).
      Measured angular distributions were obtained using ion chambers with different
      build-up caps (low and high-Z) and the sensitivity of the data to small changes
      in geometry (e.g., moving the x-ray target) was investigated. The photon energy
      fluence was calculated using EGSnrc and preliminary indications are that the
      measured and calculated distributions agree to better than 5 %. Work supported in
      part by NIH grant R01 CA104777-01A2.

PMID- 28512875
TI  - Sci-Fri PM: Planning-12: Class II division interpretation of the amended Class II
      regulations.
AB  - The proposed amendments to the Class II regulations are expected to come into
      effect in May 2008. This presentation will provide highlights of the change to
      Class II regulations and how those changes will be interpreted by the CNSC during
      licence assessments and inspections. The changes to the regulations are designed
      to correct a number of regulatory deficiencies that have come to light since the
      regulations came into force.

PMID- 28512876
TI  - Sci-Sat AM(2): Brachy-03: Monte Carlo dosimetry for I-125 and Pd-103 eye plaque
      brachytherapy.
AB  - A Monte Carlo study of dosimetry for eye plaque brachytherapy was performed.
      BrachyDose, an EGSnrc user-code which makes use of Yegin's multi-geometry
      package, was used to fully model Iodine-125 (model 6711) and Palladium-103 (model
      200) brachytherapy seeds and the standardized plaques of the Collaborative Ocular
      Melanoma Study (COMS). Three-dimensional dose distributions in the eye region
      were obtained. In general, dose to water was scored, however the implications of
      replacing water with eye materials was explored. The effect of the gold alloy
      (Modulay) backing was investigated and the dose was found to be sensitive to the
      elemental composition of the backing. The presence of the silicon polymer
      (Silastic) seed carrier resulted in substantial dose decreases relative to water,
      particularly for Pd-103. For the Modulay backing and Silastic insert combination
      in a 20 mm plaque, the dose decrease relative to water is of the order of 12% for
      I-125 and 20% for Pd-103 at a distance of 1 cm from the central seed along the
      plaque's central axis. For the configurations of seeds used in COMS plaques,
      interseed attenuation is a small effect within the eye region. The introduction
      of an air interface results in a dose reduction in its vicinity which depends on
      the plaque's position within the eye and the source type. The dose distributions
      in the eye for the two different sources were compared and, for the same
      prescription dose, Pd-103 generally offers a lower dose to critical normal
      structures.

PMID- 28512878
TI  - Sci-Sat AM(2): Brachy-09: Investigation of catheter displacement in HDR prostate
      brachytherapy.
AB  - During prostate cancer treatment with HDR brachytherapy, catheters are inserted
      into the prostate. Between planning and treatment, catheters may move inferiorly
      due to edema. If undetected, treatment proceeds without correcting the catheter
      displacement, and an incorrect treatment is delivered. The purpose of this study
      was to investigate the consequences of catheter displacement on prostate coverage
      and critical structure avoidance. Ten patient plans were selected in which
      movement of the catheters had been observed. The original treatment plan,
      generated using Nucletron PLATO (ver. 14.3.2), was adjusted introducing inferior
      catheter offsets of 5, 10, 20, and 30 mm. The original treatment dwell times were
      re-entered into the offset plans to determine the consequences of the
      displacement. DVH data was calculated for the prostate, rectum, urethra, and
      bladder. Prostate V100 decreased from 99% to 36% over the ten patients studied.
      For the urethra, the D10 increased (114.1% to 128.2%), as did the V125 (2.7% to
      12.8%). In the rectum the V75 initially increased as the catheters shifted
      inferiorly, but dropped as the shift increased beyond 10 mm. In the penile bulb
      the V75 increased as a function of shift (from 2.1% to 44.8%). Every effort
      should be made to ensure that the catheters do not move during prostate
      treatment. A small shift, 5 mm, would result in a small deviation of the dose
      distribution. In this case a re-optimization of the plan is unnecessary. Larger
      shifts will have a serious impact on the dose delivered to the prostate and to
      sensitive normal structures.

PMID- 28512877
TI  - Sci-Fri AM: YIS-04: Scatter correction of cone beam optical computed tomography
      for polymer gel dosimetry.
AB  - Optical computed tomography (OptCT) may become the preferred scanning method for
      gel dosimetry dose validations, due to its high sensitivity and relatively low
      cost. Cone beam computed tomography (CBCT) arrangements are advantageous because
      of reduced scan time. However, CBCT arrangements are more sensitive to errors
      associated with scatter than other CT configurations. Unfortunately in polymer
      gel dosimetry this problem is amplified as the primary mode of beam attenuation
      is through scatter. Thus, managing and reducing the effects of scatter remains an
      important challenge for cone beam OptCT. In this work we examine two schemes for
      reducing the effects of scatter in the Vista cone beam OptCT system. First, we
      employed a pair of anti-scatter polarizing planes to reduce the magnitude of
      stray light reaching the camera. Secondly, we implemented a beam stop array (BSA)
      sampling method -which has been successful in correcting for scatter in X-ray
      CBCT- to obtain scatter field measurements that are subtracted from CT
      projections removing veiling glare. While both implementations reduced scatter
      related artifacts, the BSA technique yielded greater improvement without obvious
      image degradation. Comparative studies between absorbing dye standards and
      colloidal scattering standards with the same spectrophotometric optical
      attenuation revealed that application of the BSA technique nullified OptCT
      measurement disagreements between scattering and absorbing systems. When the BSA
      scatter correction technique was applied to polymer gel dosimetry 3%3mm agreement
      rose from 79.2% to 99.82%. These findings underscore the strength of the BSA
      sampling technique and its utility in cone beam OptCT.

PMID- 28512879
TI  - Sci-Fri PM: Planning-05: Saving trees and improving workflow.
AB  - Patient treatment preparation is a multi-step process requiring inputs from a
      range of disciplines and technologies. Our centre generates just over 4500
      treatment plans annually and operates from two main campuses. A large, split
      program presents unique challenges during treatment preparation and has provided
      the impetus for a completely electronic treatment process. Throughout 2006 and
      2007, we migrated our external beam treatment planning to the Computerized
      Medical Systems (CMS) product line. Utilizing a thin-client architecture, CMS
      supports distributed (multi-site) planning. Coincident with the treatment
      planning upgrade, IMPAC Multi-Access was configured to provide a paperless and
      filmless treatment record and electronic patient workflow. Standardized treatment
      objectives were also implemented in the form of site-group approved care plans.
      Details of the pretreatment process and the CMS / IMPAC implementation will be
      presented as well as a workflow time analysis. To date, treatment preparation
      times have been reduced by 25% (2.5 days) as a result of workflow improvements,
      representing a clear benefit to both staff and patients.

PMID- 28512880
TI  - Sci-Sat AM(1): Imaging-04: Respiratory errors in cardiac PET/CT with manual
      alignment of the CT image.
AB  - Respiratory motion can produce misregistration errors between CT and PET images
      in cardiac PET/CT imaging. The objective of this study was to determine if manual
      registration of a single-phase end-expiration CT scan to the PET image would
      eliminate respiratory-induced artifacts. Listmode data from 71 cardiac PET
      patient scans were rebinned into a 8-frame respiratory-gated image series based
      on a respiratory trigger signal obtained with an optical tracking system. CT
      based attenuation correction (AC) was performed after registering the CT image
      with the mean position of the PET images. The 8 phases of the gated PET study
      were coregistered and the breathing motion was measured. Images from end
      inspiration and end-expiration were compared to assess the effect of motion.
      Studies in which the motion was >8mm were reconstructed again, with the CT scan
      aligned to end-expiration or end-inspiration, to determine if phase-specific
      registration could reduce the residual errors. The motion was found to be
      greatest in the axial direction (mean 4.1mm +?- 1.8mm) and 4 Rb stress studies
      (17%) had motion >8mm. The maximum displacement during breathing was greater for
      Rb-stress imaging (<15mm) than for resting (<7.5mm) or NH3-stress (<5.4mm)
      imaging. No significant differences were noted between the respiratory phases of
      the rest studies. Errors in myocardial radiotracer uptake of up to 35% were noted
      between end-inspiration and end-expiration for studies with >8mm of motion. Phase
      specific registration of the CT reduced the extent of the errors but did not
      fully resolve them, suggesting that more sophisticated AC is required.

PMID- 28512881
TI  - Poster - Thurs Eve-40: The potential of using SPECT ventilation information with
      IMRT for functional lung avoidance in radiotherapy of non small cell lung cancer.
AB  - We have investigated the feasibility of using ventilation scans obtained from
      single photon emission computed tomography (SPECT) in intensity-modulated
      radiation therapy (IMRT) planning in lung cancer radiotherapy to avoid well
      functioning lung. We fused SPECT ventilation scans acquired at GE Hawkeye SPECT
      CT of ten stage-III lung radiotherapy patients with planning CT in treatment
      planning system (Pinnacle v8.0, Philips Medical Systems). We automatically
      segment out 50% and 70% ventilated volumes. For each patient, we generated IMRT
      plans using nine equally spaced beams with and without avoiding well ventilated
      volume. They were compared with three beam IMRT plans with beam directions chosen
      to minimize the mean dose to the ventilated lung volumes, while keeping cord dose
      below tolerance and dose uniformity in the target. The plans generated using
      functional lung avoidance information reduces the doses to the functioning lung.
      With both IMRT avoidance plans, we could not obtain better functional avoidance
      or lower V-20Gy (volume receiving 20Gy or more) for total lung when the planning
      target volume (PTV) was surrounded by functional lung volumes. We were able to
      achieve better ventilated lung avoidance and lower total lung V-20Gy when the PTV
      is close to, but not surrounded by functioning lung volumes. For patients with
      the PTV that is far from 50% and 70% functional lung volumes, three-field IMRT
      spare the ventilated lung as well as nine-field IMRT ventilation avoidance plan,
      with a lower total lung V20-Gy.

PMID- 28512882
TI  - Sci-Sat AM(2): Brachy-07: Tomosynthesis-based seed reconstruction in LDR prostate
      brachytherapy: A clinical study.
AB  - To develop a tomosynthesis-based dose assessment procedure that can be performed
      after an I-125 prostate seed implantation, while the patient is still under
      anaesthesia on the treatment table. Our seed detection procedure involves the
      reconstruction of a volume of interest based on the backprojection of 7 seed-only
      binary images acquired over an angle of 60 degrees  with an isocentric imaging
      system. A binary seed-only volume is generated by a simple thresholding of the
      volume of interest. Seeds positions are extracted from this volume with a 3D
      connected component analysis and a statistical classifier that determines the
      number of seeds in each cluster of connected voxels. A graphical user interface
      (GUI) allows to visualize the result and to introduce corrections, if needed. A
      phantom and a clinical study (24 patients) were carried out to validate the
      technique. A phantom study demonstrated a very good localization accuracy of
      (0.4+/-0.4) mm when compared to CT-based reconstruction. This leads to dosimetric
      error on D90 and V100 of respectively 0.5% and 0.1%. In a patient study with an
      average of 56 seeds per implant, the automatic tomosynthesis-based reconstruction
      yields a detection rate of 96% of the seeds and less than 1.5% of false
      positives. With the help of the GUI, the user can achieve a 100% detection rate
      in an average of 3 minutes. This technique would allow to identify possible
      underdosage and to correct it by potentially reimplanting additional seeds. A
      more uniform dose coverage could then be achieved in LDR prostate brachytherapy.

PMID- 28512883
TI  - Sci-Sat AM(1): Imaging-06: Proximity-based modification to an automatic method
      for tumor delineation using MRSI.
AB  - Quantifying the relative levels of Choline (Cho) to N-Acetylaspartate (NAA) has
      been the method of choice by many groups as a mean to biologically identify
      tumors in the brain. Mcknight et al. have introduced an automatic technique for
      delineating tumors biologically using MRSI. A statistical model is used to
      separate tumors from normal tissue based on the relative concentrations of
      Choline and NAA in both tissue types; that method is commonly referred to as the
      Choline-to-NAA Index (CNI). In their work, it is assumed that the variation in
      the relative levels of Cho to NAA in normal brain is unnoticeable to within 2
      standard deviations of the mean. However, developments in MRSI sequences have
      enabled the detectablity of more variations within the relative levels of Cho to
      NAA in normal tissue. With the uncertainty in the Cho to NAA levels of normal
      tissue increasing, it is essential to modify the CNI method to improve its
      specificity. This work introduces a modification to the CNI method developed by
      McKnight et al. that would address such increase in uncertainty. Instead of
      relying on an arbitrary CNI value of 2 to define the tumor boundaries, our method
      defines a high certainty tumor volume, surrounded by a region of uncertainty.
      Then based on their proximity to high certainty tumor regions, the voxels in the
      uncertainty region are segmented to either tumor or normal tissue. Preliminary
      results suggest that the proposed modified method decreases the number of false
      positive resulting from the original CNI method.

PMID- 28512884
TI  - Poster - Thurs Eve-42: A revision of the gamma-evaluation: Initial interpretation
      of dose disagreements on gamma-vector fields.
AB  - Gamma evaluations are a common clinical tool used as a quantitative comparison
      between dose-distributions, combining both dose difference and distance to
      agreement criteria. Because gamma evaluations permit rapid analysis of agreement
      between complex dose distributions, they are often a preferred comparison method
      for assessing delivery of conformal radiotherapy distributions. Although the
      comparison provides a useful measure of agreement between distributions when the
      index is less than one, the scalar gamma value provides little information into
      the clinical significance or source of disagreements of failing gamma values
      (i.e., when gamma>1). Previously, Stock et al., have presented the gamma angle as
      an indicator of the relative influence of the distance to agreement versus the
      dose difference on gamma. We present a modification to the gamma evaluation such
      that the complete 3D gamma vector information is considered. The predictive
      nature of each vector component was investigated by simulating various dose
      disagreements in test distributions. Misalignment tests revealed that the mean
      gamma vector components indicate the offset direction and relative magnitude for
      all test distributions. The mean dose component of the gamma vector was
      prognostic of double Gaussian overdoses and underdoses in a virtual conformal
      delivery. The response of the vector field depends on properties distinctive to
      each distribution, such as the local dose gradient. Understanding how these
      unique properties affect the vector field may permit better diagnosis of dose
      disagreement sources. Other vector field properties, such as curl and divergence,
      may yet provide more information for interpreting the cause and significance of
      gamma>1.

PMID- 28512885
TI  - Sci-Fri AM: YIS-10: Development of a flat panel detector with avalanche gain for
      low-dose x-ray imaging.
AB  - Digital flat panel detectors are increasingly being used in radiography and
      fluoroscopy. The imaging performance of current systems, however, is compromised
      by electronic noise at the low X-ray exposures employed in fluoroscopy and low
      dose radiography. In other words, current flat panel detectors are not quantum
      noise limited at these low radiation exposures. There is thus a need to develop
      an imaging detector with the high sensitivity of an X-ray image intensifier and
      the inherent advantages of a solid-state flat panel detector. Towards this end,
      we have developed and characterized a novel solid-state device capable of
      providing very high avalanche gains and an excellent temporal response. The
      device which is based on the amorphous photoconductor a-Se, is scalable (i.e. can
      be manufactured in large areas), can overcome electronic noise even at the lowest
      X-ray exposures used in diagnostic imaging (0.1 MUR/frame at the detector) and
      has a very low level of dark current. Here, we investigate the gain and temporal
      characteristics of this device and discuss its applicability for low exposure X
      ray imaging as well as the effects of avalanche gain on the detective quantum
      efficiency. Coupled to a high-resolution structured CsI X-ray scintillator and a
      thin film transistor array, this device should provide a true solid-state
      alternative to the X-ray image intensifier, which is both robust and cost
      effective. This should open the door to dose-efficient flat panel imagers for
      radiography and fluoroscopy as well as a number of other demanding medical
      imaging applications.

PMID- 28512886
TI  - Sci-Fri PM: Planning-11: Selection and optimization of angiographic roadmap
      images for magnetic resonance guided catheter tracking.
AB  - As endovascular magnetic resonance (MR) techniques for device tracking and
      guidance move closer to demonstrating clinical feasibility, more investigation in
      the generation and optimization of vascular roadmap images is need to achieve the
      full benefit of MR-guided procedure. MR angiographic roadmap imaging requires
      high signal-to-noise (SNR), good vascular-to-background contrast and short
      acquisition time. These requirements not only qualify the appropriate roadmaps
      for therapy, but also guide in the optimization of their acquisition parameters.
      We hypothesize that among the well established MR angiographic techniques, low
      resolution phase-contrast (PC) images would prove satisfactory for vascular
      roadmap imaging. To verify this, four potential MR angiography techniques,
      specifically, time-of-flight, contrast-enhanced, phase-contrast and black-blood
      angiography, were explored for roadmap imaging using a canine model on a 3 T MR
      scanner. PC angiography was specifically performed to evaluate impact of key
      parameters on the SNR efficiency and vascular-to-background contrast efficiency
      in order to optimize the sequence for therapeutic use. Data were collected from
      five canines. Phase-contrast angiography was found to be most suitable for
      generating vascular roadmap for MR-guided endovascular therapy. It was also found
      that small acquisition matrix and large FOV produced satisfactory roadmap images
      provided that the size of the vessel of interest was more than a few times the in
      plane pixel dimension. Also, reducing the phase encoding steps had minimal effect
      on vessel oriented parallel to the phase encode direction.

PMID- 28512887
TI  - Sci-Sat AM(2): Brachy-02: Image guided brachytherapy (IGBT) for HDR prostate
      treatment : Pre-treatment verification using cone beam imaging to determine
      catheter displacement.
AB  - PURPOSE: Prostate HDR brachytherapy utilizes flexible catheters for treatment
      delivery. Catheters are inserted under US guidance and planning performed on CT
      images. This study investigates the efficacy of performing kV cone beam imaging
      prior to treatment to quantify catheter displacement and dose delivered.
      MATERIALS AND METHODS: Twenty consecutive patients undergoing HDR prostate
      brachytherapy were planned using CT images. Under US guidance, catheters and four
      fiducial markers were placed into the prostate. Before treatment, visual check
      confirmed no movement of the template sutured to the perineum and no movement
      relative to the template. Cone beam imaging was performed using an isocentric
      mobile c-arm. Catheters were re-adjusted if required by the Radiation Oncologist.
      The cone beam images prior to adjustment were later fused with the planning CT.
      RESULTS AND DISCUSSION: In 17 of the 20 patients, catheter displacements
      exceeding 0.5cm were observed. Compared to the CT based plan, an average catheter
      displacement of 1.0cm results in a decrease in the V100 of the prostate by
      approximately 27%, urethra V120 increased by about 7%, and urethra D10 increased
      by about 4%. Approximately 65% of patients had average catheter displacements of
      1.0cm and larger. Three patients had catheter shifts larger than 2cm.
      CONCLUSIONS: Catheter movement within the patient can be significant and cone
      beam imaging prior to treatment delivery provides precise imaging to determine
      catheter displacement. Cone beam imaging time using an isocentric C-arm is
      sufficiently short enough (~ 2 minutes) so as to make this a viable quality
      assurance tool in the OR.

PMID- 28512888
TI  - Sci-Fri AM: YIS-03: Simulated annealing optimization of the pre-target electron
      beam in Monte Carlo virtual linac models.
AB  - The purpose of this study is to develop a method for determining the initial
      parameters of the pre-target electron beam within a Monte Carlo (MC) accelerator
      model able to produce accurate 18 MV 40*40 cm2 photon field profiles. We have
      developed a novel method by which the electron beam intensity distribution can be
      reverse engineered to reproduce measured dose distributions. The method begins
      from a cylindrically symmetric pre-target electron beam (radius 0.5 cm) of
      uniform intensity. This beam is subdivided into annular regions of fluence for
      which each region is individually transported through the accelerator head and
      into a water phantom. A simulated annealing search is then performed to determine
      the optimal combination of weights of the annular fluences that provide a best
      match between measured dose distributions and the weighted sum of annular dose
      distributions. Remarkably, the intensity distribution converges to a solution
      that is predominantly Gaussian, with a FWHM=1.1mm. In addition, the solution
      contains an important secondary "extra focal halo" on the order of 10% of the
      maximum Gaussian intensity. Agreement of the 40*40 cm2 photon field profiles with
      measurement was within 0.5%. The method greatly reduces the effort required to
      commission a MC accelerator model for clinical use and has achieved better
      agreement with measurement than other methods described in the literature. Our
      derived value of the electron beam FWHM agrees with that measured by Jaffray et
      al, 1993, and the "extra focal halo" is in qualitative agreement with their
      measurements of extra focal radiation.

PMID- 28512889
TI  - Sci-Sat AM(2): Brachy-08: Monte Carlo calculations of 192Ir high dose rate
      brachytherapy treatment plans using CT and cone beam CT images.
AB  - The feasibility of using cone beam computed tomography (CBCT) images for Monte
      Carlo (MC) brachytherapy dose calculations has been investigated. To evaluate the
      effects of tissue heterogeneities and finite patient dimensions for 192Ir high
      dose rate treatment, CT-based MC calculations for breast and head and neck cases
      were first performed using the PTRAN_CT photon transport code. PTRAN_CT is an
      accelerated MC code specifically designed for patient-specific dose calculations.
      Muscles and adipose tissues, which are nearly indistinguishable in CBCT images,
      are found to cause minimal dose perturbations at 192Ir energies compared to
      water. The proximity of the tumor to the skin, however, will have an observable
      impact on the dose up to a few percent. Therefore, for CBCT calculations, a
      reasonable assignment of material and density values to the patient voxel
      geometry, with a good delineation of the skin and bony structures, will suffice
      for MC dose calculations. A CBCT-based calculation for an actual treatment plan
      with the tumor close to the cheek was performed. The results were compared to
      TG43 calculations to quantify the dose differences in the target and critical
      structures. Since the dose delivered to the tumor is mostly primary dose,
      deviations are found mostly in the organs at risk where scatter contribution
      becomes more significant. This study shows that for HDR brachytherapy
      applications, CBCT-based MC calculations is a feasible option despite inferior
      image quality and larger uncertainties in the Hounsfield Units compared to CT
      images. Research supported by Nucletron BV.

PMID- 28512890
TI  - Sci-Fri PM: Planning-04: Dose escalation study using anatomy-based aperture IMRT
      and SPECT perfusion images for lung cancer.
AB  - In the case of non-small cell lung cancer, doses typically prescribed (60-66 Gy)
      are not sufficient to ensure a satisfactory tumor control probability. Dose
      escalation needs to be realized, but dose to organs at risk (OARs) must be kept
      under widely accepted clinical thresholds. Also, lung functionality is not
      homogeneously distributed over all the volume: single-photon emission computed
      tomography (SPECT) allows spatial characterization of perfusion, open the way to
      the design of treatments plans that could preferentially avoid highly-functional
      lung. In this study, three cases of lung cancer were retrospectively used to
      assess the capacity of an anatomy-based aperture inverse planning system to
      realize dose escalation while limiting dose to perfused lung. Plans were
      generated for four-beam non-coplanar configurations, mixing 6 and 23 MV photon
      beams. All dose calculations were performed using Pinnacle3
      superposition/convolution algorithm. An increasing dose was prescribed to a
      subvolume of the initial planning target volume. Levels of escalation achieved
      for the three cases studied were 81 Gy, 111 Gy and 66 Gy to the subvolume.
      Escalation was limited in two cases by the dose to the esophagus and in the other
      case by the presence of overdosages near beam entry ports. Calculation of dose
      volume parameters for OARs shows that they respect clinical thresholds. Plans
      generated by the system are less complex than plans generated in beamlet-based
      IMRT, because of the use of few, large segments. The approach used in this study
      allows important dose escalation, potentially improving treatment outcome.

PMID- 28512891
TI  - Sci-Sat AM(1): Imaging-03: On-line dynamic contrast enhanced cone-beam CT for
      measuring.
AB  - We propose a novel on-line functional imaging method with which tumor
      microenvironment can be quantified at the treatment unit. It is an X-ray contrast
      enhanced method based the (kv) cone beam CT (CBCT) platform and it promises to
      provide a surrogate measurement of tumor perfusion. The method was tested with 6
      rabbits implanted with VX2 tumor. The technique involves a baseline CBCT followed
      by a contrast enhanced CBCT synchronized with contrast injection. The scan time
      for each CBCT is approximately 2 minutes during which a set of projections are
      acquired. The conventional reconstruction approach of contrast enhanced CBCT will
      give a single volumetric image with no temporal signature. On the other hand, the
      proposed technique makes use of a mathematical expression to parameterize the
      wash-in and wash-out behavior of contrast uptake in each voxel. Based on the
      projection data, the new method uses non-linear optimization to solve for the
      parameters describing the dynamic characteristics of injected contrast with which
      tumor perfusion can be derived. In our rabbit study, dynamic contrast enhanced
      images were reconstructed with the CBCT projections by the proposed method.
      Results show that the estimated contrast enhancement with the proposed CBCT
      method is in excellent agreement with the measured enhancement by CT. The
      proposed CBCT method is sensitive for detecting changes in the tumor
      microenvironment as a result of radiation treatment.

PMID- 28512892
TI  - Poster - Thurs Eve-39: Full 3D dose calculation for total body irradiation: A
      comparison study between treatment planning systems in homogeneous and
      heterogeneous conditions.
AB  - PURPOSE: To perform full 3D heterogeneous dose calculations for total body
      irradiation (TBI) cases and compare different treatment planning softwares (TPS).
      METHOD: A retrospective study was performed on 7 patients. Dose distributions
      obtained with Pinnacle3 v.7.9u (Philips Medical Systems) were compared with the
      ones calculated using our actual TBI planning system Theraplan Plus (TPP) by MDS
      Nordion/Nucletron. Two different Pinnacle3 models were studied: standard beam
      commissioning (std_Pinnacle3 ) and TBI commissioning (TBI_Pinnacle3 ). For the
      later case, commissioning was adapted for the special TBI conditions (extended
      SSD of 190cm, large field, acrylic beam spoiler, and out of field dose (OFD)).
      RESULTS: Significant differences are found between the TPP, std_Pinnacle3 and
      TBI_Pinnacle3 dose distributions. For the relative mid-line doses, differences up
      to 12% were observed. Systematic overestimations of 5% were found in patients
      extremities between TPP and TBI_Pinnacle3 . Average dose underestimation of 3%
      was observed between std_Pinnacle3 and TBI_Pinnacle3 . Differences in patient
      extremities are attributed to the OFD contribution which is not correctly
      computed in TPP and std_Pinnacle3 . Dose comparison outside the patient's mid
      line showed greater differences (up to 20%) between models. Accurate 3D
      heterogeneous dose calculations with TBI_Pinnacle3 model show major differences
      (homogeneous versus heterogeneous) in high and low density regions. Dose
      overestimation of 5% was observed in bony regions and dose underestimation of 5%
      to 10% was observed in lung regions. CONCLUSION: Those results are of major
      interest since they show a strong dependence of the dose calculation outcome on
      both TPS and commissioning used, potentially leading to significant dose
      misevaluation.

PMID- 28512893
TI  - Sci-Sat AM(2): Brachy-06: A Comparison of MR/CT fusion versus CT alone for
      assessment of implant quality in permanent prostate brachytherapy.
AB  - Low dose-rate permanent implant brachytherapy is widely used in the management of
      patients with early stage prostate cancer. An assessment of the implant quality
      is usually carried out 30 days after the implant is delivered, using computed
      tomography (CT) to identify the prostate and seeds. This is difficult due to poor
      contrast of the prostate and the superposition of seeds in the CT images.
      Magnetic resonance (MR) imaging offers superior contrast but inferior
      visualization of seeds. At our centre, patients are imaged using both CT and T2
      weighted MR 30 days after an implant, and the image sets are fused using a
      commercial software package. The seeds are identified on CT and the prostate
      volumes are contoured on MR, with fusion performed by matching seeds on CT with
      seed signal voids on MR. The purpose of this study was to compare standard
      prostate post-implant dosimetric parameters (D90, V100, etc.) for prostates
      contoured on CT alone (MR blinded) versus MR/CT fusion. 25 patients were
      evaluated with all contouring performed by the same physician. We found that the
      prostate volume was overestimated using CT alone as compared to MR/CT fusion
      (mean: 37.2cc vs. 35.0cc respectively, p = 0.033). We also found that dosimetric
      parameters were underestimated for CT alone compared to MR/CT fusion, including
      D90 (mean: 144.3Gy vs. 150.8Gy respectively, p = 0.005) and V100 (mean: 89.2% vs.
      91.0% respectively, p = 0.01). Centres using CT alone for post-implant dosimetry
      may therefore be underestimating their implant quality.

PMID- 28512894
TI  - Sci-Fri AM: YIS-07: A new paradigm for improving IMRT: Selection of beam
      orientations by optimizing beam intersection volume.
AB  - A beam orientation optimization (BOO) algorithm based on optimizing beam
      intersection volume (BIV) components within an Organ-at-Risk (OAR) is proposed to
      improve conventional intensity-modulated radiation therapy (IMRT). A simulated
      annealing algorithm was employed to search for the optimal set of five beam
      orientations (5-opt) which simultaneously minimize the BIV components within an
      OAR. The 5-opt plans were compared to standard 5, 7, and 9 equiangular-spaced
      beam plans (5-equi, 7-equi, 9-equi) for: (1) gastric (2) Radiation Therapy
      Oncology Group (RTOG) P-0126 prostate and (3) RTOG H-0022 oropharyngeal (Stage
      III, IV) cancer patients. In the gastric case, the coplanar 5-opt plan reduced
      the right kidney V 20 Gy by 41.1%, 32.1%, and 29.5% compared to the 5-equi, 7
      equi, and 9-equi plans. In the prostate case, the coplanar 5-opt plan improved
      rectal sparing over all standard plans with a reduction of the V 75 Gy, V 70 Gy,
      V 65 Gy, and V 60 Gy of 3.9%, 6.2%, 8.1%, and 10.6% compared to the 5-equi plan.
      In both oropharyngeal cases, the non-coplanar 5-opt plan substantially reduced
      the V 30 Gy and mean dose to the contralateral parotid compared to the 5-equi, 7
      equi, and 9-equi plans: (Stage-III) 8.9%, 7.0%, 8.6% and 4.1 Gy, 2.5 Gy, 2.7 Gy
      (Stage-IV) 11.2%, 11.2%, 10.8% and 7.8 Gy, 7.9 Gy, 8.0 Gy. In conclusion, the
      method of optimizing BIV to produce substantial improvements in OAR sparing over
      conventional IMRT has been demonstrated to be robust for application to a variety
      of IMRT treatment sites.

PMID- 28512895
TI  - Poster - Thurs Eve-41: Imaging and radiation delivery in helical tomotherapy:
      Phantom study of a moving target.
AB  - Treating lung cancer with radiation therapy by guaranteed delivery of the
      prescription dose to the target is difficult due to tumour motion. The standard
      approach to account for motion effects consists of adding a substantial margin to
      a lesion visible on the CT study. Larger irradiated volume results in increased
      dose deposition in healthy lung and the potential for patient complications. This
      investigation focuses on determining the optimal choice of planning CT mode for
      improved radiation delivery in terms of better target coverage and sparing of
      healthy organs. Dosimetric measurements were performed on a helical tomotherapy
      unit. A Quasar(r) (Modus Medical Devices, London, ON) respiratory phantom was
      imaged while a polystyrene target moved sinusoidally with a period of 4 s and
      amplitude of 2 cm. For target moving in superior-inferior and lateral directions,
      conventional fast-CT image studies were created, as well as maximum intensity
      projection (MIP) and average intensity projection (AveIP) image studies using
      four-dimensional CT information. All types of CT studies were used to develop
      treatment plans with a prescription of 2 Gy per fraction to the target outlined
      according to the imaged data. Measurements of dose deposition were made in four
      locations within the moving target using an Exradin A1SL ion chamber. Comparing
      all results to the dose measured at the centre of the static phantom, the MIP
      plans overdose the target, the fast-CT results vary from case to case, while the
      AveIP plans provide consistent dose distribution across the target within 2% of
      the normalization dose.

PMID- 28512897
TI  - Sci-Fri PM: Planning-10: The replacement correction factors for cylindrical
      chambers in megavoltage beams.
AB  - The replacement correction factor (Prepl ) in ion chamber dosimetry accounts for
      the effects of the medium being replaced by the air cavity of the chamber. In TG
      21, Prepl was conceptually separated into two components: fluence correction, Pfl
      , and gradient correction, Pgr . In TG-51, for electron beams, the calibration is
      at dref where Pgr is required for cylindrical chambers and Pfl is unknown and
      assumed to be the same as that for a beam having the same mean electron energy at
      dmax . For cylindrical chambers in high-energy photon beams, Prepl also
      represents a major uncertainty in current dosimetry protocols. In this study,
      Prepl is calculated with high precision (<0.1%) by the Monte Carlo method as the
      ratio of the dose in a phantom to the dose scored in water-walled cylindrical
      cavities of various radii (with the center of the cavity being the point of
      measurement) in both high energy photon and electron beams. It is found that, for
      electron beams, the mean electron energy at depth is a good beam quality
      specifier for Pfl ; and TG-51's adoption of Pfl at dmax with the same mean
      electron energy for use at dref is proven to be accurate. For Farmer chambers in
      photon beams, there is essentially no beam quality dependence for Prepl values.
      In a Co photon beam, the calculated Prepl is about 0.4-0.6% higher than the TG-21
      value, indicating TG-21 (and TG-51) used incorrect values of Prepl for
      cylindrical chambers.

PMID- 28512896
TI  - Sci-Fri AM: YIS-09: The effect of magnetic interference on a coupled MR-linac
      system: Optimization of 3D FEM linac model.
AB  - PURPOSE: The coupling of a 0.2T bi-planar Magnetic Resonance Imager and medical
      linear accelerator (linac) is proposed to provide real-time Image Guided
      Radiotherapy. This coupling necessitates the linac to be within the fringe fields
      of the bi-planar magnets causing magnetic interference. The design and
      optimization of the minimum required shielding is necessary to reduce the fringe
      field magnitudes to a point where a clinically useful radiation beam is produced.
      METHOD: A first step to designing shielding is the full 3D radio-frequency
      modeling of the linac waveguide using the Finite Element Method. Various
      optimizations were performed on the linac model in order to achieve a desired
      resonant frequency, pi/2 phase shift per cavity and other desired properties. An
      accelerating cavity (AC) and coupling cavity (CC) was first optimized in 3D to
      have identical resonant frequencies before the full 3D model was generated.
      RESULTS: In order to increase the capture efficiency of the injected electrons,
      the electric field in the first AC was reduced by shifting the first CC towards
      the gun end of the linac. The input waveguide AC dimensions were adjusted to
      account of the additional coupling iris and the last full AC had its gap length
      decreased. CONCLUSION: This work is the first step to determining the minimum
      magnetic shielding required to produce a clinically useful radiation beam from a
      coupled MR-Linac system. The fully optimized 3D model more accurately calculates
      the electric and magnetic field values since it includes the effects of coupling.

PMID- 28512898
TI  - Sci-Sat AM(2): Brachy-01: A novel HDR Ir-192 brachytherapy water calorimeter
      standard.
AB  - Parameters influencing the accuracy of absorbed dose measurements for HDR 192Ir
      brachytherapy using water calorimetry were investigated with the goal to develop
      a novel primary absorbed dose to water standard. To provide greater stability,
      flexibility, and accuracy in the source-detector distance dsrc-det positioning
      and measurement, a new spring-loaded catheter holder composed of two concentric
      cylindrical sleeves with multiple orthogonal adjusting screws was developed. The
      absorbed dose from Nucletron microSelectron-HDR 192Ir brachytherapy sources with
      air kerma strengths ranging between 21000-38000 U was studied. dsrc-det is
      optimized so as to balance signal-to-noise ratio (decreasing with increasing dsrc
      det ) and temperature drift effects resulting from source self-heating. The
      irradiation times were adjusted to yield a minimum 1 Gy of dose at the
      measurement point. Successful measurements at dsrc-det ranging between 25-50 mm
      were performed. COMSOL MULTIPHYSICSTM software was used to determine the heat
      loss correction due to conduction defined as the ratio between temperature rise
      at a point under ideal conditions to realistic conditions (i.e., no conduction).
      An agreement of better than 6.5% was observed between TG-43 calculated and
      calorimetrically measured absorbed dose rates. The effects of convection where
      calculated to be negligible as the glass vessel provides a convective barrier
      significantly decoupling the water velocity in the interior and exterior of the
      vessel (water velocities were 1-2 orders of magnitude different). Our work paves
      the way to successful primary absorbed dose determination for radioactive sources
      using calorimetric techniques.

PMID- 28512899
TI  - Sci-Fri AM: YIS-02: Evaluation of the LabPET4 imaging capabilities for in vivo
      small animal imaging.
AB  - Positron Emission Tomography (PET) is a non-invasive technique to visualize
      metabolic and physiological processes in vivo. Excellent imaging capabilities
      such as spatial resolution and count rate performance are essential to achieve
      accurate information about the observed processes. It is for this purpose that
      the LabPET scanner, an avalanche photodiode (APD)-based fully digital scanner PET
      scanner, was initially developed. Two variants of the scanner exist: LabPET4 and
      LabPET8 with 3.75 and 7.5 cm axial lengths respectively. The range of the
      transaxial FOV is up to 10 cm therefore it can easily accommodate mice and rats.
      The aim of this work is to evaluate LabPET4 imaging in several phantoms and small
      animals. Spatial resolution was determined using a point source and hot spots
      phantoms. The latter were used to assess recovery coefficients (RC) obtained by
      taking the ratio of hot spot maximum values compared to the biggest spot maximum
      value. FBP reconstructed tangential/radial resolution is 1.3/1.4 mm FWHM (2.5/2.4
      FWTM) at the field of view center. With an Ultra Micro Hot Spot Phantom, 1 mm
      spots are clearly resolved. Count rate performance was obtained for mouse-size
      and rat-size phantoms. For mouse phantom, scatter fraction is 18%, noise
      equivalent count rate (NEC) peak is 120 kcps at 5.6 mCi and true coincidences
      peak is 215 kcps at 6.6 mCi. Mice and rats were imaged with Na18F and 18FDG.
      LabPET4 imaging capabilities achieve state-of-the-art requirements for molecular
      imaging and therefore can provide excellent quality images.

PMID- 28512900
TI  - Sci-Fri PM: Planning-03: Fundamental understanding of the inter-relation of arc
      range, angular dose rate and MLC leaf position optimization of Intensity
      Modulated Arc Therapy for a concave target.
AB  - Intensity Modulated Arc Therapy (IMAT) is a rotational variant of Intensity
      Modulated Radiation Therapy (IMRT) that can be implemented with or without
      angular dose rate optimization. The purpose of this study is to determine the
      inter-relationship among arc range, Multi-Leaf Collimator (MLC) leaf positions
      and angular dose rate optimizations for IMAT delivery of a concave target. A
      concave planning target volume (PTV) with central cylindrical organ at risk (OAR)
      was used in dissecting the inter-relationships. Plans with full and limited arc
      range were generated using leaf position optimization (LPO) alone, angular dose
      rate optimization (ADRO) alone or LPO followed by ADRO. Two initial IMAT arcs
      were conformal avoidance arcs created with 5 degrees  angular increments where
      MLC leaf positions were determined from the beams eye view to irradiate the PTV
      but avoid the OAR. The objective function value (evaluating dose to PTV and OAR),
      a conformity index, dose homogeneity index, mean dose to OAR and normal tissues
      were computed and used to evaluate the treatment plans. Dose rate variations and
      MLC leaf movements as a function of gantry angle were examined in this approach.
      The results demonstrate that LPO followed by ADRO provided the lowest objective
      function values, best conformity and dose homogeneity indices, and third in mean
      dose to OAR and normal tissues for the complete arc range. Future work will
      address different strategies for simultaneously optimizing both the MLC leaf
      positions and the variable angular dose rate for IMAT delivery and compare single
      and multiple arc plans.

PMID- 28512901
TI  - Sci-Sat AM(1): Imaging-02: Comparison between experimental measurements and Monte
      Carlo simulations for the off-focal radiation in diagnostic x-ray systems.
AB  - In a typical x-ray tube, off-focal radiation is mainly generated by the
      backscattered electrons that re-enter the anode outside the focal spot. In an
      earlier study, the EGSnrc/BEAMnrc system was modified to be able to properly
      transport the anode backscattered electrons, and to tally their subsequent
      generation of off-focal x-rays. In the current study, a diagnostic system and a
      recent digital mammography system are simulated using the modified BEAMnrc code,
      and the simulation results are compared with experimental measurements from the
      literature. Simulation results show excellent agreement with experimental
      measurements for the spectral shape of both the primary and the off-focal
      components, and also for the integral off-focal-to-primary ratio. The spectrum of
      the off-focal component at the patient plane is softer than the primary, which
      causes a slight softening in the overall spectrum. For a given configuration, the
      off-focal component increases with tube voltage because of the increased
      probability for off-focal x-rays to escape the anode self-filtration and the
      total filtration. This study validates our earlier implementation of off-focal
      radiation in EGSnrc/BEAMnrc, and provides a well-benchmarked tool that simulates
      x-ray tubes more realistically. The macro to add this feature to BEAMnrc is
      available from the authors.

PMID- 28512902
TI  - Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two
      iodine seeds in LDR brachytherapy.
AB  - PURPOSES: This work consists of studying the interseed and tissue composition
      effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model
      seed. MATERIALS & METHODS: Three seeds were modeled with the MCNP MC code in a
      water sphere to evaluate the interseed effect. The dose calculated at different
      distances from the centre was compared to the dose summed when the seeds were
      simulated separately. The tissue composition effect was studied calculating the
      radial dose function for different tissues. Before carrying out post-implant
      studies, the absolute dose calculated by MC was compared to experiment results:
      with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed
      in a water tank. Afterwards, the TG-43 approximation effects were studied for a
      prostate and breast post-implant. RESULTS AND DISCUSSION: The interseed effect
      study shows that this effect is more important for model 6711 (15%) than for IBt
      (10%) due to the silver rod in 6711. For both seed models the variations of the
      radial dose function as a function of the tissue composition are quasi similar.
      The absolute dose comparisons between MC calculations and experiments give good
      agreement (inferior to 3% in general). For the prostate and breast post-implant
      studies, a 10% difference between MC calculations and the TG-43 is found for both
      models of seeds. CONCLUSION: This study shows that the differences in dose
      distributions between TG43 and MC are quite similar for the two models of seeds
      and are about 10% for the studied post-implant treatments.

PMID- 28512903
TI  - Sci-Fri AM: YIS-06: On-line adaptive radiation therapy based on the intra
      fractional digital tomosynthesis images.
AB  - PURPOSE: To investigate the feasibility of performing on-line adaptive radiation
      therapy (ART) based on the intra-fractional digital tomosynthesis (DTS) images.
      METHOD AND MATERIALS: Intra-fractional DTS images were reconstructed as the
      gantry rotated between treatment positions. An edge detection algorithm was used
      to automatically segment the DTS images as the gantry arrived at each treatment
      position. The original treatment plan was then re-optimized for the most recent
      DTS image contours and dose was delivered from each treatment position based on
      the newly re-optimized plan. Plan re-optimization was performed using modified
      direct aperture optimization (DAO). To test our system, a model representing
      typical prostate, bladder and rectum anatomy was generated. First, a treatment
      plan based on this original anatomy was created using our DAO system. To simulate
      prostate deformations, three clinically relevant deformations (small, medium and
      large) were modeled by systematically deforming the original anatomy. The ability
      of our approach to adapt the original treatment plan and account for the anatomy
      deformations was investigated. RESULTS: Based on the dose-volume constraints from
      the RTOG 0415 prostate protocol, the original treatment plan would have been
      clinically unacceptable for all three deformations. Using our approach to on-line
      ART, the original treatment plan was successfully adapted to arrive at a
      clinically acceptable plan for all three anatomy deformations. CONCLUSION: We
      have shown that performing on-line ART based on intra-fractional DTS images is
      feasible. The advantages are reduced treatment time and the ability to detect and
      account for patient motion during the treatment fraction.

PMID- 28512904
TI  - Sci-Fri PM: Planning-07: A low diffusion radiochromic gel dosimeter for three
      dimensional radiation dosimetry.
AB  - PURPOSE: To develop a low diffusion radiochromic leuco crystal violet (LCV)
      hydrogel utilizing micelles, for three-dimensional (3-D) radiation dosimetry.
      METHOD AND MATERIALS: Concentrations of LCV dye, Triton X-100 and trichloroacetic
      acid were varied to determine the optimal gel sensitivity for optical computed
      tomography (CT). Using a laser optical CT scanner at lambda = 594 nm, diffusion
      rate measurements were performed on half-irradiated (6 MV x-rays) cuvette gel
      samples made with and without surfactant, respectively. A cylindrical 1 L gel
      volume was irradiated with a 12 MeV electron beam (Varian Clinac 2100C) to a dose
      of 30 Gy and scanned with cone- beam optical CT at lambda ~ 590 nm (VistaTM,
      Modus Medical Devices Inc.). RESULTS: The most radiation sensitive gel
      formulation was found to be: 1 mM LCV, 4 mM Triton X-100, 30 mM trichloroacetic
      acid and 4% gelatin. The diffusion rates of a LCV gel without and with surfactant
      present were about 2 and 20 times lower than the Fricke xylenol-orange gel
      system, respectively. Comparison of the central axis gel attenuation coefficients
      normalized at depth of maximum dose (dmax ) with TG21-corrected ion chamber data,
      were in agreement, thus, indicating energy and dose-rate independence.
      CONCLUSION: Radiochromic LCV micelle gels show minimal diffusion effects and a
      dose response that is linear, energy and dose-rate independent. Optical CT
      scanned LCV micelle gels are a promising system for 3-D dose verification.
      CONFLICT OF INTEREST: Two of the authors (JB, KJ) have a licensing agreement with
      Modus Medical Devices Inc. concerning the commercialization of VistaTM.

PMID- 28512905
TI  - Sci-Fri AM: YIS-08: Prototype fan beam optical computed tomography scanner for
      three-dimensional dose verification in radiation therapy.
AB  - A prototype, rapid, high precision fan beam optical computed tomography (OptCT)
      scanner for three-dimensional polymer gel dosimetry of complex radiotherapy
      protocols has been developed. The scanner employs a sixty degree fan beam of 543
      nm laser light to interrogate irradiated gel samples up to 19 cm in cross
      sectional diameter. Rapid data acquisition with minimal scattered light and
      minimal refraction and reflection artefacts is achieved with the unique radial
      design of the front and back apertures of the index matching medium tank,
      concentric arrangement of a CNC machined collimator and five photodiode detector
      arrays for light detection. Characteristics of the scanner include: an SNR of
      optical absorbance in light field projections of up to 100:1; SNR of optical
      absorbance in transmission projections of up to 92:1 for phantoms with
      absorbances ranging from 0.1 to 1.0 and a spatial resolution of 0.25 mm. OptCT
      dose maps extracted from normoxic NIPAM polymer gels irradiated with (a) a
      rectangular 3*3 cm2 field, (b) a 4-field wedged treatment and (c) a C-shaped IMRT
      plan are examined and compared to the Eclipse TPS. For these treatments, dose
      resolution is examined in steep and moderate dose gradient regions using dose
      difference and gamma function metrics. The effect of different OptCT
      reconstruction parameters on ring and streaking artefacts is also demonstrated.

PMID- 28512906
TI  - Sci-Fri PM: Planning-09: An EGSnrc investigation of ion chamber response to Co-60
      beams.
AB  - The EGSnrc Monte Carlo code was evaluated for its ability to calculate the
      relative response of a variety of ion chambers to Co-60 beams as a means of
      justifying the use of this code in future investigations of cavity theory. EGSnrc
      calculations were compared to measurements with four separate ion chambers, which
      were each configured with several wall materials (ranging from plastic to lead)
      and cavity sizes (or cavity air pressures). The experimental results included
      measurements by Nilsson et al. in 1992, and experiments by Whyte, Attix et al.
      and Cormack and Johns in the mid-to-late 1950's designed to evaluate Spencer
      Attix cavity theory. Experiments by Whyte involved measurements of the response
      per unit mass as a function of cavity air pressure for a large cylindrical
      chamber, whereas the other experiments consisted of measurements of the response
      per unit mass (or ionization current) as a function of the distance between the
      front and back wall (cavity height) of a plane-parallel chamber. EGSnrc
      calculations, which could account for the change in response associated with
      changes in wall material in most cases, were generally within 1-3% of
      experimental values, even for experimental data that required calculations of
      unreported wall corrections determined using experimental techniques. The ability
      of EGSnrc to accurately model these experiments, which showed variations up to
      300%, confirms its suitability for detailed Monte Carlo studies of cavity theory.

PMID- 28512907
TI  - Sci-Sat AM(1): Imaging-08: Small animal APD PET detector with submillimetric
      resolution for molecular imaging.
AB  - Visualization and quantification of biological processes in mice, the preferred
      animal model in most preclinical studies, require the best possible spatial
      resolution in positron emission tomography (PET). A new 64-channel avalanche
      photodiode (APD) detector module was developed to achieve submillimeter spatial
      resolution for this purpose. The module consists of dual 4 * 8 APD arrays mounted
      in a custom ceramic holder. Individual APD pixels having an active area of 1.1 *
      1.1 mm2 at a 1.2 mm pitch can be fitted to an 8 * 8 LYSO scintillator block
      designed to accommodate one-to-one coupling. An analog test board with four 16
      channel preamplifier ASICs was designed to be interfaced with the existing LabPET
      digital processing electronics. At a standard APD operating bias, a mean energy
      resolution of 27.5 +/- 0.6% was typically obtained at 511 keV with a relative
      standard deviation of 13.8% in signal amplitude for the 64 individual pixels.
      Crosstalk between pixels was found to be well below the typical lower energy
      threshold used for PET imaging applications. With two modules in coincidence, a
      global timing resolution of 5.0 ns FWHM was measured. Finally, an intrinsic
      spatial resolution of 0.8 mm FWHM was measured by sweeping a 22Na point source
      between two detector arrays. The proposed detector module demonstrates promising
      characteristics for dedicated mouse PET imaging at submillimiter resolution.

PMID- 28512908
TI  - Sci-Fri AM: YIS-01: Comprehensive MR distortion correction: Phantom validation
      and in-vivo application.
AB  - MR images provide excellent diagnostic information; however, their treatment
      planning utility is limited due to geometric uncertainties from both system and
      patient related sources. Despite this concern, interest in developing MR-based
      treatment planning protocols is on the rise because of the ease with which
      clinically relevant structures can be identified in MR. Here we present our
      systematic approach to quantifying both machine (gradient non-linearity and B0
      inhomogeneity) and patient (susceptibility and chemical shift) distortions.
      Gradient non-linearities were previously measured using a 3D grid phantom while
      the remaining types of distortion were measured using a double gradient echo scan
      to obtain a B0 distortion map specific to each object/patient. Distortion
      measurement and correction were validated on phantoms and then implemented on a
      volunteer. B0 inhomogeneity and susceptibility distortions were simulated by
      offsetting the x2 -y2 shims; maximum absolute distortion was reduced from 5.4 mm
      to 1.0 mm and mean (+/- standard deviation) was reduced from 1.7 +/- 1.4 mm to
      0.4 +/- 0.2 mm. Chemical shift distortion was qualitatively evaluated using a
      phantom containing fat and water inserts; displacement of the fat signal was much
      improved following distortion correction. Intensity correction was validated
      using a uniformity phantom and undistorted image profiles were compared to
      distorted image profiles and to profiles corrected for geometric and
      geometric/intensity distortion; the need for intensity correction was clearly
      demonstrated. Once all types of distortion correction were validated on phantoms,
      the technique was implemented on a volunteer brain image. Both GE and multi-shot
      EPI images were corrected.

PMID- 28512909
TI  - Sci-Fri PM: Planning-02: MRI-based radiation treatment planning for an MRI-linac
      system.
AB  - At Cross Cancer Institute, we are investigating a novel MRI-linac system
      consisting of a bi-planar 0.2 T permanent magnet coupled with a 6 MV Linac. The
      system can freely revolve axially around the patient to deliver dose from any
      desired angle. For such a system, the radiation treatment planning procedure is
      expected to rely on the MR images only, i.e. MRI Simulation. Replacing the
      current CT/CT+MRI-based RTP procedure with MRI Simulation will eliminate the need
      for the planning CT scanning sessions (no additional x-ray exposure) and
      consequently the image fusion between MRI and planning CT. In this work, we
      propose a comprehensive MRI-based RTP procedure for an MRI-Linac system.
      Specifically, the method consists of a) data acquisition, b) analysis and
      correction of image artifacts caused by the scanner-related and patient-induced
      distortions, c) segmentation of organ structures relevant to dosimetric
      calculations (e.g. soft tissue, bone, air), d) conversion of MR images into CT
      like images by assigning bulk electron density values to organ contours defined
      at step c), e) dose calculations in external magnetic field, and f) plan
      evaluation. Monte Carlo simulations were performed to determine the linac-MRI
      scanner's magnetic field induced effects on the dose deposited patterns using
      patient data. Specifically, we investigated the dosimetric differences between
      the corresponding MRI-based RT plans simulated at zero and 0.2 T. We found that
      the maximum percent differences for brain studies were within 4%. Most of these
      differences occurred at the inferior field edge and superficially at beam exits.

PMID- 28512910
TI  - Sci-Sat AM(1): Imaging-01: Tumour and normal tissue T2 and ADC distributions for
      a mouse model at 9.4T.
AB  - Magnetic resonance (MR) measurements of relaxation times and diffusion
      coefficient in tissue have been demonstrated to be sensitive to biological
      changes induced by radiation therapy. We are currently using mouse models of
      human glioblastoma multiforme (GBM) to study tumour response to ionizing
      radiation by MRI at 9.4T. Utilizing conventional imaging techniques coupled with
      quantitative measurements of transverse relaxation time (T2) and apparent
      diffusion coefficient (ADC), we monitor changes during tumour growth and
      subsequent changes after single-fraction radiotherapy. In addition to tumour
      parameters, we have measured T2 and ADC in other structures that appear in the
      same transverse slices as tumour tissue. Here we report the measured
      distributions of T2 and ADC in tumour and in normal tissues that are likely to be
      encountered during MR imaging of tumour xenografts in mice, including liver,
      kidney, fat, skeletal muscle, spinal cord, and brain. Quantitative knowledge of
      these distributions in normal tissue is important in optimizing the sequences
      used for imaging of these tissues, and in optimizing continued measurements of T2
      and ADC changes. Knowledge of parameter distributions in tumour is important
      because recent studies have suggested that the T2 and ADC responses after therapy
      may be the result of large shifts in smaller isolated pockets of tumour, rather
      than more moderate shifts in T2 and ADC over the whole tumour volume. These
      distributions provide a baseline measurement of typical distributions in advance
      of radiation therapy.

PMID- 28512911
TI  - Sci-Sat AM(2): Brachy-04: Spectral and dosimetric study of the Xoft electronic
      brachytherapy system.
AB  - The Axxent developed by Xoft Inc. is a miniature x-ray tube capable of generating
      a 50 kVp x-ray spectrum with dose-rates suitable for HDR applications. Results of
      spectral measurements compared with Geant4 Monte Carlo simulations have been
      published. This study is a continuation of previous work with shifting emphasis
      towards dosimetric characterization of the miniature x-ray tube. Dose
      distributions using EBT Gafchromic films agree to within 10 % of Geant4 results.
      In addition, TG-43 parameters can be calculated. However, consideration should be
      given to the biological effectiveness of the spectrum at different depths.
      Spectral measurements show significant beam hardening with 1st HVL increasing
      from 0.55 to 1.20 mm Al after 11.50 mm of water filtration. This effect may be
      attributed to the significant loss of low energy characteristic photons.
      Furthermore, the degree of beam hardening is dependent of the material, with 1st
      HVLs of 1.20 and 1.03 mm Al after 11.50 mm of water and Lucite respectively. The
      biological effect is quantified by calculating the number of single and double
      strand breaks. The number of strand breaks for the 50 kVp x-ray spectrum is
      similar to that of I-125 radiation.

PMID- 28512912
TI  - Sci-Fri AM: YIS-05: A new guidance device for lateral-approach stereotactic
      breast biopsy.
AB  - Stereotactic breast biopsy (SBB) is the gold standard for noninvasive breast
      cancer diagnosis. Current systems rely on one of two methods for needle
      insertion: a top-approach (from above the breast compression plate) or a lateral
      approach (parallel to the compression plate). While the top-approach is more
      commonly used, it is not feasible in patients with thin breasts (less than 2.5 cm
      thickness after compression), or with superficial lesions. We present a novel
      design of lateral guidance support for SBB, which addresses these limitations of
      the top-approach, and provides improvements over existing lateral support
      hardware. This device incorporates spherical linkages to allow two degrees of
      rotational freedom in the needle trajectory for increased targeting flexibility,
      as well as an adjustable rigid needle support to minimize needle deflection
      within the tissue. Needle placement error in SBB experiments is compared using
      both the new lateral guidance device and a commercial lateral guidance device in
      agar phantoms. The effect of elevation angle on needle placement accuracy using
      the new lateral guidance device is also assessed. Finally, a biopsy accuracy
      experiment is presented using a certified SBB phantom to compare the new design
      and the commercial lateral guidance device. In these experiments, SBB performed
      using the new lateral guidance device results in improved needle placement error
      and biopsy accuracy, while increasing targeting flexibility and maintaining
      procedural workflow.

PMID- 28512913
TI  - Sci-Fri PM: Planning-06: Verification of a Monte Carlo based treatment planning
      system in a homogeneous water phantom.
AB  - In this abstract we present the results of the verification of the XVMC based
      treatment planning system "PrecisePLAN" (release 2.50; Elekta). We investigated a
      6 MV photon beam from an Elekta Synergy linear accelerator in a homogeneous water
      phantom. Measurements of profiles, percentage depth dose curves (pdds) and
      relative output factors (ROFs) for square fields of sides 3, 5, 7, 10, 15, 20 and
      30 cm were compared to calculations performed with PrecisePLAN and simulations
      with BEAMnrc and DOSXYZnrc. Following recommendations from the literature we
      investigated the deviations between measurements and calculations of the profiles
      and pdds in four regions and checked for the criterion of acceptability (given in
      parenthesis): the inner region (3 %, 2 % at the central axis), the penumbra (2 mm
      distance to agreement), the outer region (3 %) and the build up region (2 mm).
      The mean deviation +/- 1.5 times the standard deviation should lie within the
      confidence interval of the thresholds quoted above. For the ROFs we found very
      good agreement with the measurement. The deviations are lower than two and one
      percent for PrecisePLAN and BEAMnrc, respectively, for the investigated field
      sizes. Also most of the profiles and pdds fulfill the criteria of acceptability
      given above, but for the large field sizes some of the profiles and pdds fall
      outside the threshold values. The overall agreement between measurements and
      calculations, especially for the clinically relevant situations in modern
      conformal/IMRT techniques, is clinically acceptable.

PMID- 28512914
TI  - Sci-Sat AM(1): Imaging-05: Analytical scatter estimation for cone-beam computed
      tomography.
AB  - A significant challenge to the implementation of cone-beam computed tomography
      (CBCT) for high-resolution imaging is the high scatter to primary ratio. Scatter
      causes cupping and shading artifacts, increased noise and decreased contrast in
      reconstructed images. Methods to reduce the impact of scatter in CBCT are thus
      very desirable. We are investigating methods for computational scatter estimation
      and compensation for CBCT, with the goal of incorporating a scatter estimator
      within a statistical reconstruction algorithm. We have developed an analytical
      method for estimating single scatter, based on Klein-Nishina cross-sections. We
      have compared scatter estimates generated with this method with the results of
      high-count EGSnrc Monte Carlo simulations. The analytical estimates compare
      favorably with the Monte Carlo estimates. The paper will discuss our method for
      analytical estimation of single scatter, including the assumptions and
      simplifications required to render it computationally tractable, along with the
      results of the comparison between the analytical method and Monte Carlo
      simulations. The paper will extend previous results obtained with small (40 * 40
      * 40 voxel) homogeneous computational phantoms to include results for larger,
      more clinically relevant phantoms (128 * 128 * 128 voxels, simulated 50/50 breast
      tissue with inserts of varying contrast). The paper will also discuss
      computational acceleration obtained through the use of parallel processing via
      the WestGrid High-Performance Computing network.

PMID- 28512915
TI  - BOOKS AND PUBLICATIONS.

PMID- 28512916
TI  - Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.
AB  - Tryptophan, an essential amino acid through a series of enzymatic reactions gives
      rise to various metabolites, viz. serotonin and melatonin, that regulate distinct
      biological functions. We show here that tryptophan metabolism in the pineal gland
      favors bone mass accrual through production of melatonin, a pineal-derived
      neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes
      the first step in the melatonin biosynthesis lead to a decrease in melatonin
      levels and a low bone mass due to an isolated decrease in bone formation while
      bone resorption parameters remained unaffected. Skeletal analysis of the mice
      deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice
      while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone
      mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and
      bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/
      and MT2-/- mice showed a cell intrinsic defect in the proliferation,
      differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT
      counterparts, and the mutant cells did not respond to melatonin addition.
      Finally, we demonstrate that daily oral administration of melatonin can increase
      bone accrual during growth and can cure ovariectomy-induced structural and
      functional degeneration of bone by specifically increasing bone formation. By
      identifying pineal-derived melatonin as a regulator of bone mass through MT2
      receptors, this study expands the role played by tryptophan derivatives in the
      regulation of bone mass and underscores its therapeutic relevance in
      postmenopausal osteoporosis.

PMID- 28512918
TI  - Postpartum contraceptive choices among women attending a well-baby clinic in
      Ghana.
AB  - OBJECTIVE: To assess postpartum contraceptive choices among women attending a
      well-baby clinic in Ghana. METHODS: From April 1 to May 31, 2011, a descriptive
      cross-sectional survey was conducted among women who attended the well-baby
      clinic of Komfo Anokye Teaching Hospital, Kumasi, at 6-24 months after delivery.
      Participants were consecutively recruited and interviewed using semi-structured
      questionnaires. Data were collected on demographics, exposure to family planning
      counseling, message content, and postpartum contraceptive choices. Differences
      between the profiles of women who did or did not take up postpartum family
      planning were assessed. RESULTS: Of the 200 women enrolled, 44 (22.0%) wanted no
      more children and the last pregnancy was unintended among 88 (44.0%). In all, 110
      (55.0%) women took up postpartum contraception, with the calendar method (n=57;
      51.8%) and injectable contraceptives (n=22; 20.0%) cited as popular choices.
      Family planning counseling was received at the prenatal clinic by 47 (23.5%)
      women, with 12 (6.0%) given written referrals on the postnatal ward. More
      previous contraceptive users than previous non-users chose long-acting or
      permanent postpartum methods (P<0.001). CONCLUSION: Inadequate postpartum family
      planning counseling and referrals during maternity care were recorded, suggesting
      that a comprehensive educational intervention is required to improve uptake.

PMID- 28512919
TI  - Influence of serum lipids on the incidence and progression of diabetic
      retinopathy and macular oedema: Sankara Nethralaya Diabetic Retinopathy
      Epidemiology And Molecular genetics Study-II.
AB  - IMPORTANCE: The importance of lipids on incidence and progression of diabetic
      retinopathy has not been studied in the Indian population. BACKGROUND: To
      elucidate the influence of serum lipid control on the incidence and progression
      of diabetic retinopathy and diabetic macular oedema in subjects with type 2
      diabetes. DESIGN: Population-based longitudinal observational study in a hospital
      setting. PARTICIPANTS: Eight hundred ninety subjects were examined at baseline
      and follow-up. METHODS: Diabetic retinopathy was graded per Modified Early
      Treatment Diabetic Retinopathy Study scales; 45 degrees , 4-field dilated
      stereoscopic digital photography was performed with an additional 30 degrees , 7
      field for those who had retinopathy. Macular oedema was evaluated per Proposed
      International Clinical Diabetic Retinopathy and Diabetic Macular Oedema Disease
      Severity Scales. MAIN OUTCOME MEASURES: Association of serum lipids and incidence
      and progression of diabetic retinopathy. RESULTS: Poor control of total
      cholesterol was associated with the incidence of sight-threatening retinopathy
      (odds ratio = 7.2 [95% confidence interval: 1.5-34.3], P = 0.012) and macular
      oedema (odds ratio = 5.5 [95% confidence interval: 1.4-27.4], P = 0.037) after
      adjusting for potential confounders. Poor control of triglycerides was associated
      with progression to proliferative diabetic retinopathy (odds ratio = 3.2 [95%
      confidence interval: 1.1-10.5], P = 0.048). Risk for incident macular oedema (P =
      0.041) and progression to proliferative diabetic retinopathy (P = 0.028) was
      greater when all lipid types were abnormal. CONCLUSIONS AND RELEVANCE: Poor
      control of lipids is a risk factor for incidence of and progression to late
      stages of retinopathy. Abnormal levels of all lipid types are associated with
      risk of incident macular oedema and progression to proliferative diabetic
      retinopathy.

PMID- 28512917
TI  - Nomenclature for factors of the HLA system, update February 2017.

PMID- 28512920
TI  - An audit of adherence to heart failure guidelines in an Australian hospital: A
      pharmacist perspective.
AB  - RATIONALE, AIMS, AND OBJECTIVES: The Australian National Heart Foundation
      Guidelines have been developed to guide clinicians on how to best manage chronic
      heart failure (CHF) patients according to the current best available evidence.
      The primary aim of this study is to evaluate the proportion of patients
      prescribed evidence-based therapy (EBT) for CHF on discharge at this Australian
      metropolitan hospital and factors affecting its prescribing. The secondary aims
      are to examine the proportion of patients prescribed EBT on discharge on cardiac
      wards compared to medical wards and to explore the role of the pharmacist in the
      management of these patients. METHOD: A retrospective audit of patients' medical
      notes who were admitted consecutively for CHF management was conducted over 6
      months to examine their management. RESULTS: The results showed at discharge, a
      total of 52% of patients were discharged on angiotensin converting enzyme
      inhibitors/angiotensin receptor blockers, 49% were discharged on beta-blockers,
      15% were on Aldosterone receptor antagonists, 90% were discharged on diuretics,
      and 29% were discharged on Digoxin. The main determinants of prescribing EBT on
      discharge were the presence of prescribing contraindications and patients'
      comorbidities. Patients discharged from cardiac wards were more likely to be
      prescribed EBT than if discharged on medical wards. Furthermore, in the subset of
      the cohort who was reviewed by a pharmacist during admission, a higher percentage
      of patients were discharged on EBT compared with those who did not have a
      pharmaceutical input. CONCLUSION: This study highlighted existing gaps between
      the National CHF Guidelines and clinical prescribing practice in this hospital.
      Patients who were discharged from cardiac wards were more likely to be prescribed
      medications concordant with the guidelines, and there is further opportunity for
      pharmacists to assist in closing gaps in prescribing practice by the promotion of
      adherence to these guidelines.

PMID- 28512921
TI  - Web-based integrated bipolar parenting intervention for parents with bipolar
      disorder: a randomised controlled pilot trial.
AB  - BACKGROUND: People with bipolar disorder (BD) experience additional parenting
      challenges associated with mood driven fluctuations in communication, impulse
      control and motivation. This paper describes a novel web-based self-management
      approach (Integrated Bipolar Parenting Intervention; IBPI) to support parents
      with BD. METHOD: Parents with BD with children aged 3-10 years randomised to IBPI
      plus treatment as usual (TAU) or waitlist control (WL). IBPI offered 16 weeks
      access to interactive self-management information concerning BD and parenting
      issues. Feasibility was through recruitment, retention and web usage. Clinical
      outcomes were assessed at baseline, 16, 24, 36 and 48 weeks. TRIAL REGISTRATION
      NUMBER: ISRCTN75279027. RESULTS: Ninety seven participants were recruited with
      98% retention to end of intervention and 90% to final follow-up (56%-94% data
      analysed of retained participants; higher rates for observer measures). 77% of
      IBPI participants accessed the website (53% accessed parenting modules). Child
      behaviour, parenting sense of competence and parenting stress improved
      significantly in IBPI compared to WL to end of intervention, sustained to 48
      weeks. Impacts of IBPI on family functioning, parent mood and time to mood
      relapse were not significant. CONCLUSIONS: Online self-management support for
      parents with BD is feasible, with promising improvements in parenting and child
      behaviour outcomes. A definitive clinical and cost-effectiveness trial is
      required to confirm and extend these findings.

PMID- 28512922
TI  - Effect of chemical immobilization of SDF-1alpha into muscle-derived scaffolds on
      angiogenesis and muscle progenitor recruitment.
AB  - The availability of three-dimensional bioactive scaffolds with enhanced
      angiogenic capacity that have the capability to recruit tissue specific resident
      progenitors is of great importance for the regeneration of impaired skeletal
      muscle. Here, we have investigated whether introduction of chemoattractant
      factors to tissue specific extracellular matrix promotes cellular behaviour in
      vitro as well as muscle progenitor recruitment and vascularization in vivo. We
      developed an interconnective macroporous sponge from decellularized skeletal
      muscle with maintained biochemical traits of the intact muscle. SDF-1alpha, a
      potent cell homing factor involved in muscle repair, was physically adsorbed or
      chemically immobilized in these muscle-derived sponges. The immobilized sponges
      showed significantly higher SDF-1alpha conjugation efficiency along with improved
      metabolism and infiltration of muscle-derived stem cells in vitro, and thus
      generated uniform cellular constructs. In vivo, femoral muscle implantation in
      rats revealed a negligible immune response in all scaffold groups. We observed
      enhanced engraftment, neovascularization, and infiltration of CXCR4+ cells in the
      immobilized-SDF-1alpha sponge compared with nonimmobilized controls. Although
      Pax7+ cells identified adjacent to the immobilized-SDF-1alpha implantation site,
      other factors appear to be necessary for efficient penetration of Pax7+ cells
      into the sponge. These findings suggest that immobilization of cell homing
      factors via chemical mediators can result in recruitment of cells to the
      microenvironment with subsequent improvement in angiogenesis.

PMID- 28512923
TI  - The Braden Scale, A standard tool for assessing pressure ulcer risk, predicts
      early outcomes after liver transplantation.
AB  - The Braden Scale is a standardized tool to assess pressure ulcer risk that is
      reported for all hospitalized patients in the United States per requirements of
      the Center for Medicare and Medicaid Services. Previous data have shown the
      Braden Scale can predict both frailty and mortality risk in patients with
      decompensated cirrhosis. Our aim was to evaluate the association of the Braden
      Scale score with short-term outcomes after liver transplantation (LT). We
      performed a retrospective cohort study of deceased donor LT recipients at 2
      centers and categorized them according to the Braden Scale at hospital admission
      as low (>18), moderate (16-18), or high risk (<16) for pressure ulcer. We created
      logistic and Poisson multiple regression models to evaluate the association of
      Braden Scale category with in-hospital and 90-day mortality, length of stay
      (LOS), nonambulatory status at discharge, and discharge to a rehabilitation
      facility. Of 341 patients studied, 213 (62.5%) were low risk, 59 (17.3%) were
      moderate risk, and 69 (20.2%) were high risk. Moderate- and high-risk patients
      had a greater likelihood for prolonged LOS, nonambulatory status, and discharge
      to a rehabilitation facility, as compared with low-risk patients. High-risk
      patients additionally had increased risk for in-hospital and 90-day mortality
      after LT. Multiple regression modeling demonstrated that high-risk Braden Scale
      score was associated with prolonged LOS (IRR, 1.56; 95% confidence interval [CI],
      1.47-1.65), nonambulatory status at discharge (odds ratio [OR], 4.15; 95% CI,
      1.77-9.71), and discharge to a rehabilitation facility (OR, 5.51; 95% CI, 2.57
      11.80). In conclusion, the Braden Scale, which is currently assessed in all
      hospitalized patients in the United States, independently predicted early
      disability-related outcomes and greater LOS after LT. Liver Transplantation 23
      1153-1160 2017 AASLD.

PMID- 28512925
TI  - Nitrogen-fixing tree abundance in higher-latitude North America is not
      constrained by diversity.
AB  - The rarity of nitrogen (N)-fixing trees in frequently N-limited higher-latitude
      (here, > 35 degrees ) forests is a central biogeochemical paradox. One hypothesis
      for their rarity is that evolutionary constraints limit N-fixing tree diversity,
      preventing N-fixing species from filling available niches in higher-latitude
      forests. Here, we test this hypothesis using data from the USA and Mexico. N
      fixing trees comprise only a slightly smaller fraction of taxa at higher vs.
      lower latitudes (8% vs. 11% of genera), despite 11-fold lower abundance (1.2% vs.
      12.7% of basal area). Furthermore, N-fixing trees are abundant but belong to few
      species on tropical islands, suggesting that low absolute diversity does not
      limit their abundance. Rhizobial taxa dominate N-fixing tree richness at lower
      latitudes, whereas actinorhizal species do at higher latitudes. Our results
      suggest that low diversity does not explain N-fixing trees' rarity in higher
      latitude forests. Therefore, N limitation in higher-latitude forests likely
      results from ecological constraints on N fixation.

PMID- 28512931
TI  - Characterization of a C60o unit at a secondary standard dosimetry laboratory:
      Monte Carlo simulations compared to measurements and results from the literature.
AB  - PURPOSE: To compare a Monte Carlo (MC) characterization of a C60o unit at the
      Swedish Secondary Standard Dosimetry Laboratory (SSDL) with the results of both
      measurements and literature with the aims of (1) resolving a change in the ratio
      of air-kerma free in air Kair and absorbed dose to water Dw in a water phantom
      noted experimentally after a source exchange in the laboratory and (2) reviewing
      results from the literature on similar MC simulations. Although their use in
      radiotherapy is decreasing, the characteristics of C60o beams are of interest
      since C60o beams are utilized in calibrating ionization chambers for the absolute
      dosimetry of radiotherapy beams and as reference radiation quality in evaluating
      the energy dependence of radiation detectors and in studies on radiobiological
      effectiveness. METHODS: The BEAMnrc MC code was used with a detailed geometrical
      model of the treatment head and two models of the C60o source representing the
      sources used before and after source exchange, respectively. The active diameters
      of the C60o sources were 1.5 cm in pellet form and 2.0 cm in sintered form.
      Measurements were performed on the actual unit at the Swedish SSDL. RESULTS:
      Agreement was obtained between the MC and the measured results within the
      estimated uncertainties for beam profiles, water depth-dose curve, relative air
      kerma output factors, and for the ratios of Kair/Dw before and after source
      exchange. The on-axis energy distribution of the photon fluence free in air for
      the unit loaded with its present (1.5 cm in diameter) source agreed closely with
      the results from the literature in which a source of the same make and active
      diameter, inside a different treatment head, was simulated. The spectrum for the
      larger (2.0 cm in diameter) source was in close agreement with another published
      spectrum, also modeling a C60o source with an active diameter of 2.0 cm inside a
      different treatment head. CONCLUSIONS: The reduction in the value of Kair/Dw
      following source exchange was explained by the spectral differences between the
      two sources that were larger in the free in-air geometry used for Kair
      calibrations than at 5g/cm2 depth in the water phantom used for Dw calibrations.
      Literature review revealed differences between published in-air C60o spectra
      derived for sources of different active diameters, and investigators in need of
      an accurately determined C60o in-air spectrum should be aware of differences due
      to source active diameter.

PMID- 28512983
TI  - A radiobiological investigation on dose and dose rate for permanent implant
      brachytherapy of breast using I125 or P103d sources.
AB  - PURPOSE: The present report addresses the question of what could be the
      appropriate dose and dose rate for I125 and P103d permanent seed implants for
      breast cancer as monotherapy for early stage breast cancer. This is addressed by
      employing a radiobiological methodology, which is based on the linear quadratic
      model, to identify a biologically effective dose (BED) to the prescription point
      of the brachytherapy implant, which would produce equivalent cell killing (or
      same cell survival) when compared to a specified external radiotherapy scheme.
      METHODS: In the present analysis, the tumor and normal tissue BED ratios of
      brachytherapy and external radiotherapy are examined for different combinations
      of tumor proliferation constant (K), alpha/beta ratios, initial dose rate (R0),
      and reference external radiotherapy scheme (50 or 60 Gy in 2 Gy per fraction).
      The results of the radiobiological analysis are compared against other reports
      and clinical protocols in order to examine possible opportunities of improvement.
      RESULTS: The analysis indicates that physical doses of approximately 100-110 Gy
      delivered with an initial dose rate of around 0.05Gyh-1 and 78-80 Gy delivered at
      0.135Gyh-1 for I125 and P103d permanent implants, respectively, are equivalent to
      50 Gy external beam radiotherapy (EBRT) in 2 Gy per fraction. Similarly, for
      physical doses of approximately 115-127 Gy delivered with an initial dose rate of
      around 0.059Gyh-1 and 92 Gy delivered at 0.157Gyh-1 for I125 and P103d,
      respectively, are equivalent to 60 Gy EBRT in 2 Gy per fraction. It is shown that
      the initial dose rate required to produce isoeffective tumor response with 50 or
      60 Gy EBRT in 2 Gy per fraction increases as the repopulation factor K increases,
      even though repopulation is also considered in EBRT. Also, the initial dose rate
      increases as the value of the alpha/beta ratio decreases. The impact of the
      different alpha/beta ratios on the ratio of the tumor BEDs is significantly large
      for both the I125 and P103d implants with the deviation between the
      alpha/beta=10.0Gy ratios and those using the 4.0 and 3.5 Gy values ranging
      between 18% and 22% in most of the cases. CONCLUSIONS: For the cases of I125 and
      P103d, the equivalent physical doses to 50 Gy EBRT in 2 Gy per fraction are
      associated with an overdosage of the involved normal tissue in the range of 4%
      16% and an underdosage by 10%-15% for a BED for normal tissue, using an
      alpha/beta value of 3.0 Gy (BEDNT,3Gy) of 100 Gy. These values are lower by 10%
      20% than the published value of 124 Gy for I125 and by about 13% when compared to
      the published isoeffective dose of 90 Gy for P103d. Similarly, the equivalent
      physical doses to 60 Gy EBRT in 2 Gy per fraction are associated with an
      overdosage of the involved normal tissue by 10%-20% and an underdosage by 4%-10%
      for BEDNT,3Gy of 110 Gy.

PMID- 28512986
TI  - Work climate and the mediating role of workplace bullying related to job
      performance, job satisfaction, and work ability: A study among hospital nurses.
AB  - AIM: To increase understanding of workplace bullying and its relation to work
      climate and different outcomes among nurses. Examine a proposed bullying model
      including both job resource and job demands, as well as nurse outcomes reflected
      in job performance, job satisfaction, and work ability. BACKGROUND: Workplace
      bullying has been identified as some of the most damaging mechanisms in workplace
      settings. It is important to increase understanding of workplace bullying in
      relation to work climate and different outcomes among nurses. DESIGN: This study
      adopted a cross-sectional web based survey design. METHOD: A sample of 2946
      Registered Nurses from four public Norwegian hospitals were collected during
      October 2014. We analysed data using descriptive statistics, correlations,
      Cronbach's alpa, confirmatory factor analyses, and structural equation modelling.
      RESULTS: The majority of work climate characteristics confirmed to influence
      workplace bullying, and additionally had direct influence on nurse outcomes; job
      performance, job satisfaction, and work ability. Bullying had a mediational role
      between most of the work climate dimensions and nurse outcomes. CONCLUSION: This
      study increases our understanding of organizational antecedent of bullying among
      nurses. Workplace bullying among nurses functions as a mediator between the
      majority of work climate dimensions and outcomes related to job satisfaction and
      work ability. Strategies to reduce bullying should look at the study finding and
      specifically job resources and job demands that influence bullying and nurse
      outcomes.

PMID- 28512988
TI  - Phytochemistry and Pharmacology of Phyllanthus niruri L.: A Review.
AB  - Phyllanthus niruri, a typical member of family Euphorbiaceae, is a small annual
      herb found throughout the tropical and subtropical regions of both hemispheres.
      The genus Phyllanthus has been used in traditional medicine for its wide range of
      pharmacological activities like antimicrobial, antioxidant, anticancer,
      antiinflammatory, antiplasmodial, antiviral, diuretic and hepatoprotective. This
      review summarizes the information about morphological, biochemical,
      ethanobotanical, pharmacological, biological and toxicological activities with
      special emphasis on mechanism of anticancer activity of P. niruri. Gaps in
      previous studies such as taxonomic inconsistency of P. niruri, novel
      phytochemicals and their therapeutic properties, especially mechanisms of
      anticancerous activity and market products available, have been looked into and
      addressed. Scientific information related to 83 phytochemicals (including many
      novel compounds detected recently by the authors) has been provided in a very
      comprehensive manner. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28512989
TI  - The 'golden goddess' of spices: a potentially effective topical therapy for Bowen
      disease?

PMID- 28512990
TI  - Luminescence, circular dichroism and in silico studies of binding interaction of
      synthesized naphthylchalcone derivatives with bovine serum albumin.
AB  - Chalcones possess various biological properties, for example, antimicrobial, anti
      inflammatory, analgesic, antimalarial, anticancer, antiprotozoal and
      antitubercular activity. In this study, naphthylchalcone derivatives were
      synthesized and characterized using 1 H NMR 13 C NMR, Fourier transform infrared
      and mass techniques. Yields for all derivatives were found to be >90%. Protein
      drug interactions influence the absorption, distribution, metabolism and
      excretion (ADME) properties of a drug. Therefore, to establish whether the
      synthesized naphthylchalcone derivatives can be used as drugs, their binding
      interaction toward a serum protein (bovine serum albumin) was investigated using
      fluorescence, circular dichroism and molecular docking techniques under
      physiological conditions. Fluorescence quenching of the protein in the presence
      of naphthylchalcone derivatives, and other derived parameters such as association
      constants, number of binding sites and static quenching involving confirmed non
      covalent binding interactions in the protein-ligand complex were observed.
      Circular dichroism clearly showed changes in the secondary structure of the
      protein in the presence of naphthylchalcones, indicating binding between the
      derivatives and the serum protein. Molecular modelling further confirmed the
      binding mode of naphthylchalcone derivatives in bovine serum albumin. A site
      specific molecular docking study of naphthylchalcone derivatives with serum
      albumin showed that binding took place primarily in the aromatic low helix and
      then in subdomain II. The dominance of hydrophobic, hydrophilic and hydrogen
      bonding was clearly visible and was responsible for stabilization of the complex.

PMID- 28512991
TI  - Is parity a risk factor for excessive weight gain during pregnancy and postpartum
      weight retention? A systematic review and meta-analysis.
AB  - The aim of this study was to systematically review and meta-analyse the
      associations between parity, pre-pregnancy body mass index (BMI), gestational
      weight gain (GWG) and, when included, postpartum weight retention (PPWR). Papers
      reporting associations between parity and BMI and/or GWG in adult women were
      eligible: 2,195 papers were identified, and 41 longitudinal studies were included
      in the narrative synthesis; 17 studies were included in a meta-analysis. Findings
      indicated that parity was associated positively with pre-pregnancy BMI. In
      contrast, the role of parity in GWG was less clear; both positive and negative
      relationships were reported across studies. Parity was not associated directly
      with PPWR. This pattern of results was supported by our meta-analysis with the
      only significant association between parity and pre-pregnancy BMI. Overall,
      parity was associated with higher pre-pregnancy BMI; however, the role of parity
      in GWG and PPWR remains unclear, and it is likely that its influence is indirect
      and complex. Further research to better understand the contribution of parity to
      maternal obesity is warranted.

PMID- 28512992
TI  - Association of CD8+ T-cells with bone erosion in patients with rheumatoid
      arthritis.
AB  - AIM: Bone erosion is a major problem worsening quality of rheumatoid arthritis
      (RA) patients' lives. However, causal factors responsible for bone erosion in RA
      have remained unclear. We aimed to examine genetic variants conferring bone
      erosion in RA using a Korean genome-wide association study (GWAS) and to search
      for possible biological mechanisms underlying the development of bone erosion.
      METHOD: We obtained genome-wide single nucleotide polymorphism (SNP) data for 711
      Korean RA patients using Illumina HapMap 550v3/660W arrays. Associations between
      SNPs and bone erosion status based on the Steinbrocker staging system were
      examined using multivariate logistic regression. Cell-type-specific enrichment of
      the epigenomic chromatin annotation H3K4me3 at the bone erosion associated
      variants was further investigated using National Institute of Health Roadmap
      Epigenomics data. RESULTS: As we tested the associations between 439 289 SNPs and
      bone erosion in 385 patients with erosive RA and 326 with non-erosive RA, none of
      the tested SNPs reached the genome-wide significance threshold, although many
      loci showed modest genetic effect on bone erosion status with suggestive
      association (e.g., rs2741200 [P = 3.75 * 10-6 ] in the SLA-TG locus and
      rs12422918 [P = 4.13 * 10-6 ] in SRGAP1). However, the top-ranked SNPs and their
      linked proxies, which were mostly located in non-coding variants, were
      significantly co-localized with the highly tissue-specific regulatory marker
      H3K4me3 in CD8+ memory T-cells (P = 0.014). CONCLUSION: Although, there was no
      large-effect variants associated with bone erosion in our GWAS, we have shown
      that CD8+ memory T-cells may have relevance with bone erosion in patients with RA
      through the analysis of ChiP-seq data.

PMID- 28512993
TI  - HLA-Cw6-positive patients with psoriasis show improved response to methotrexate
      treatment.
AB  - It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type
      1) psoriasis have increased severity and reduced age of onset of psoriasis.
      However, not much is known about any differential response of this genetic
      subgroup to various treatments. We set out to determine if there was any genetic
      association of the HLA-Cw6 allele with the first-line systemic treatment commonly
      used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland
      was recruited through a novel generic consenting process (GoShare); they were
      extensively phenotyped and analysed for an association of their HLA-Cw6 genotype
      status with treatment outcomes. HLA-Cw6+ patients showed notably improved
      response to methotrexate (P = 0.05), and further analysis demonstrated an even
      greater response in a subcohort of the HLA-Cw6+ patients, who did not have
      concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited
      fewer treatment-limiting adverse events. In addition to these findings, the
      methodology and primary clinical outcome phenotype, which we validate here, will
      greatly facilitate replication of the present results in independent cohorts.

PMID- 28512994
TI  - Erythema elevatum diutinum presenting with palmoplantar keratoderma.

PMID- 28512995
TI  - Alpha-1-antitrypsin deficiency-related panniculitis: two cases with diverse
      clinical courses.
AB  - Alpha-1-antitrypsin deficiency (AATD)-related panniculitis is an extremely rare
      and underdiagnosed entity, and there is a paucity of data on its treatment. We
      report two cases of AATD-related panniculitis. The first was a 24-year-old woman
      with known AATD who presented with painful leg ulcers refractory to treatment
      with corticosteroids and colchicine. She had a good response to alpha1
      antitrypsin infusions but required dose adjustment due to flares in disease
      activity. The second case was a 38-year-old woman who presented with painful
      nodules on the legs refractory to corticosteroid therapy. Laboratory
      investigations revealed severe AATD. She had an excellent response to colchicine
      therapy. In both these cases of AATD, panniculitis was the first clinical
      manifestation of the disease. AATD-related panniculitis may have none of the
      typical clinical clues for AATD, such as a family history, cirrhosis or
      emphysema. Early identification may help prevent these complications from
      developing.

PMID- 28512996
TI  - ZL006 promotes migration and differentiation of transplanted neural stem cells in
      male rats after stroke.
AB  - New strategies must be developed to resolve the problems of stroke treatment. In
      recent years, stem cell-based therapy after stroke has come into the public and
      academic lens. Previously we have shown that uncoupling neuronal nitric oxide
      synthase (nNOS) from the postsynaptic density protein-95 (PSD-95) by ZL006, a
      small molecular compound, can ameliorate ischemic damage and promote neuronal
      differentiation of endogenous neural stem cells (NSCs) in focal cerebral ischemic
      male rats. In this study, we transplanted exogenous NSCs into the ipsilateral
      hemisphere of male rats in combination with ZL006 treatment after ischemic
      stroke. We show that ZL006 treatment facilitates the migration of transplanted
      NSCs into the ischemia-injured area and promotes neuronal differentiation of
      these cells, which is not due to a direct effect of ZL006 on exogenous NSCs but
      is associated with increased phosphorylation of cAMP response element-binding
      protein (CREB) in neurons and favorable microenvironment. Moreover, improved
      functional outcome in the ZL006-treated group was also found. Taken together, our
      data indicate that ZL006, uncoupling nNOS-PSD-95 in neurons, positively regulates
      the fate of transplanted NSCs and benefits the functional outcome after stroke in
      male rats.

PMID- 28512997
TI  - Research publication performance of Australian Professors of Nursing & Midwifery.

PMID- 28512999
TI  - In response to Otolaryngology workforce analysis.

PMID- 28512998
TI  - Implementation of Treat-to-Target in Rheumatoid Arthritis Through a Learning
      Collaborative: Results of a Randomized Controlled Trial.
AB  - OBJECTIVE: Treat-to-target (TTT) is an accepted paradigm for the management of
      rheumatoid arthritis (RA), but some evidence suggests poor adherence. The purpose
      of this study was to test the effects of a group-based multisite improvement
      learning collaborative on adherence to TTT. METHODS: We conducted a cluster
      randomized quality-improvement trial with waitlist control across 11 rheumatology
      sites in the US. The intervention entailed a 9-month group-based learning
      collaborative that incorporated rapid-cycle improvement methods. A composite TTT
      implementation score was calculated as the percentage of 4 required items
      documented in the visit notes for each patient at 2 time points, as evaluated by
      trained staff. The mean change in the implementation score for TTT across all
      patients for the intervention sites was compared with that for the control sites
      after accounting for intracluster correlation using linear mixed models. RESULTS:
      Five sites with a total of 23 participating rheumatology providers were
      randomized to intervention and 6 sites with 23 participating rheumatology
      providers were randomized to the waitlist control. The intervention included 320
      patients, and the control included 321 patients. At baseline, the mean TTT
      implementation score was 11% in both arms; after the 9-month intervention, the
      mean TTT implementation score was 57% in the intervention group and 25% in the
      control group (change in score of 46% for intervention and 14% for control; P =
      0.004). We did not observe excessive use of resources or excessive occurrence of
      adverse events in the intervention arm. CONCLUSION: A learning collaborative
      resulted in substantial improvements in adherence to TTT for the management of
      RA. This study supports the use of an educational collaborative to improve
      quality.

PMID- 28513000
TI  - A hit to current "hit" wisdom: A century later, it's time for a change.

PMID- 28513001
TI  - The frequency of urinary tract infection and subclinical bacteriuria in dogs with
      allergic dermatitis treated with oclacitinib: a prospective study.
AB  - BACKGROUND: Oclacitinib is a selective Janus kinase inhibitor for the treatment
      of canine allergic pruritus and atopic dermatitis in dogs. Glucocorticoids and
      ciclosporin increase urinary tract infection (UTI) frequency in dogs with
      inflammatory skin disease. OBJECTIVE: Prospective study to evaluate the frequency
      of UTI and subclinical bacteriuria in dogs with allergic dermatitis receiving
      oclacitinib. METHODS: Client-owned dogs >=2 years of age with a history of
      allergic dermatitis without apparent history of urinary tract disease or
      predisposition to UTI were included. Prior to enrolment, urinalysis and
      quantitative urine culture were performed after a washout period of at least 14
      days from systemic antimicrobial drugs and 28 days for ciclosporin and systemic
      glucocorticoids. Dogs received oclacitinib at labelled dosing for an intended
      period of 180-230 days with a follow-up urinalysis and urine culture performed
      regardless of urinary tract signs. Systemic antimicrobial and immune-modulating
      drugs were not administered during the study. RESULTS: None of the 55 dogs in
      this study developed UTI while receiving oclacitinib based on follow-up
      urinalysis and urine culture performed during a range of 58-280 days (mean 195
      days). Two dogs developed self-limiting abnormal urinary tract signs without
      urine culture or urinalysis findings consistent with UTI. CONCLUSIONS AND
      CLINICAL IMPORTANCE: These findings indicate that bacteriuria is not an expected
      adverse effect in dogs treated with oclacitinib without a prior history of UTI or
      predisposing condition during this treatment period. Therefore, routine urine
      culture is not indicated for such dogs in the absence of abnormal urinalysis or
      clinical signs of urinary tract disease.

PMID- 28513002
TI  - One oxygen breath shortened the time to return of spontaneous circulation in
      severely asphyxiated piglets.
AB  - AIM: Asphyxiated neonates should be resuscitated with air, but it remains unclear
      if oxygen supplementation is needed in ineffectively ventilated newborn infants.
      We studied the return of spontaneous circulation (ROSC) with oxygen or air in an
      experimental model of inadequate ventilation. METHODS: Asphyxia was induced in 16
      newborn piglets until their heart rate was <60 bpm or mean arterial pressure
      (MAP) <30 mmHg. During the first 10 minutes of resuscitation, they received one
      breath per minute of oxygen (n = 8) or air (n = 8). Tidal volume was 7.5 mL/kg.
      If MAP was <30 mmHg for 15 seconds, closed-chest cardiac massage (CCCM) was
      performed for 45 seconds. From 10 minutes onward, all piglets received normal
      ventilation with air. ROSC was defined as a heart rate >150 bpm, MAP >40 mmHg and
      no subsequent CCCM. RESULTS: Before resuscitation, the median arterial pH was
      6.73. At 10 minutes, no piglets in the oxygen group needed CCCM, while all did in
      the air group (p < 0.001). The median time to ROSC was 60 seconds with oxygen and
      845 seconds with air (p < 0.001). No brain tissue hyperoxia occurred. CONCLUSION:
      When ventilation was inadequate, one oxygen breath reduced time to ROSC in
      piglets with severe metabolic and respiratory acidosis.

PMID- 28513003
TI  - Quantification of skin erythema response to topical alcohol in alcohol-intolerant
      East Asians.
AB  - BACKGROUND/PURPOSE: Severe alcohol intolerance characterized by flushing,
      headache, nausea, and tachycardia even after very modest oral alcohol
      consumption, is common among East Asians (Chinese, Japanese, Koreans) and has
      been associated with the accumulation of acetaldehyde resulting from genetic
      polymorphism of aldehyde dehydrogenase (ALDH). These individuals also display
      erythema of the skin in response to exposure to topical alcohol. We have recently
      observed that dietary phytochemicals such as sulforaphane can accelerate the
      disposal of acetaldehyde from cells and animals by inducing ALDH. The goal of
      this study was to quantify the erythema response of skin to topical alcohol
      exposure. METHODS: The erythema response of the forearm skin of healthy Japanese
      with unusual alcohol sensitivity evoked by a range of very low doses of alcohol
      (2, 4, 8, and 16 MUmol/cm2 ) was determined by means of a chromometer, which
      measures a* values (red-green scale). RESULTS: The magnitude of the a* response
      (?a*) to alcohol was time- and dose-dependent, but differed considerably among
      individuals. It was much higher in those individuals who claimed to be alcohol
      intolerant, and ?a* was unrelated to the initial a* values of the skin prior to
      alcohol challenge. CONCLUSION: The ?a* index is suitable for the quantitative
      determination of topical alcohol-induced erythema response, and the evaluation of
      effectiveness of protective strategies against erythema response.

PMID- 28513005
TI  - Effects of argument quality, source credibility and self-reported diabetes
      knowledge on message attitudes: an experiment using diabetes related messages.
AB  - BACKGROUND: Previous studies have reported that credibility and content (argument
      quality) are the most critical factors affecting the quality of health
      information and its acceptance and use; however, this causal relationship merits
      further investigation in the context of health education. Moreover, message
      recipients' prior knowledge may moderate these relationships. OBJECTIVES: This
      study used the elaboration likelihood model to determine the main effects of
      argument quality, source credibility and the moderating effect of self-reported
      diabetes knowledge on message attitudes. METHODS: A between-subjects experimental
      design using an educational message concerning diabetes for manipulation was
      applied to validate the effects empirically. A total of 181 participants without
      diabetes were recruited from the Department of Health, Taipei City Government.
      Four group messages were manipulated in terms of argument quality (high and low)
      * source credibility (high and low). RESULTS: Argument quality and source
      credibility of health information significantly influenced the attitude of
      message recipients. The participants with high self-reported knowledge
      participants exhibited significant disapproval for messages with low argument
      quality. CONCLUSION: Effective health information should provide objective
      descriptions and cite reliable sources; in addition, it should provide accurate,
      customised messages for recipients who have high background knowledge level and
      ability to discern message quality.

PMID- 28513004
TI  - Effects of encapsulated porcine islets on glucose and C-peptide concentrations in
      diabetic nude mice 6 months after intraperitoneal transplantation.
AB  - BACKGROUND: In patients with type 1 diabetes, allogeneic islet transplantation
      can provide normal HbA1c concentrations, but it requires immunosuppression.
      Transplanting encapsulated islets into the peritoneal cavity could reduce or
      eliminate the need for immunosuppression. One of the uncertain features of
      intraperitoneal islet transplantation is the difficulty of measuring C-peptide
      concentrations in peripheral blood, which is often used for the marker of islet
      function. We hypothesized that secreted C-peptide from intraperitoneally
      transplanted islets was mostly consumed in the peritoneal cavity, which resulted
      in low C-peptide concentrations in peripheral blood. METHODS: In each of two
      experiments, encapsulated neonatal porcine islets were intraperitoneally
      transplanted into four nude mice with streptozotocin-induced diabetes. Three
      diabetic nude mice without transplanted islets were used as diabetic controls,
      and three untreated healthy nude mice were used as normal controls. Islet
      functions were monitored for 2 months in the first experiment and 6 months in the
      second experiment. Encapsulated islets were retrieved after each experiment and
      evaluated by fluorescein diacetate/propidium iodide tests for the viability and
      static glucose-stimulated insulin release tests for the function. C-peptide
      concentrations from the blood and from the intraperitoneal cavity at 6 months
      were compared. RESULTS: In both experiments, diabetes was reversed in all
      transplanted mice, and oral glucose tolerance test showed improved profiles. In
      general, retrieved islets were viable and functional. However, blood porcine C
      peptide concentrations were low at both 2 and 6 months, and concentrations in the
      ascites of peritoneal cavity were 40 times as high as those in blood.
      CONCLUSIONS: The peripheral blood sampling for c-peptide, though highly
      informative in vascularized grafts, may not be the primary tool for monitoring
      the health and function of encapsulated products when transplanted into
      intraperitoneal cavity. Our results might explain the clinical feature of the low
      C-peptide blood concentrations after successful intraperitoneal encapsulated
      islet transplantation.

PMID- 28513027
TI  - Sci-Thurs PM: Delivery-02: Improving image quality produced by CCD cameras
      exposed to stray radiation from a medical linac.
AB  - PURPOSE: Charge coupled devices (CCDs) are increasingly used in radiation
      therapy. CCDs are ideal for applications such as two-dimensional dosimetry of
      scintillator sheets or to read arrays of miniature scintillation detectors.
      However, CCDs are sensitive to stray radiation. Radiation-induced noise strongly
      alters images and limits their quantitative analysis. We have characterized
      radiation-induced noise and developed filtration algorithms to restore image
      quality. METHOD AND MATERIALS: Two models of CCD cameras were used for
      measurements in linac environments. Images were acquired with and without
      radiation. The structure of the transient noise was characterized. Then, four
      methods of noise filtration were compared: median filtering of a time series of
      images, uniform median filtering of single images, an adaptive filter with
      switching mechanism and a modified version of the adaptive filter. RESULTS: The
      intensity distribution of noisy pixels was similar in both cameras. However, the
      spatial distribution of the noise was different: the average noise cluster size
      was 1.2+/-0.6 and 3.2+/-2.7 pixels for each of the two cameras. The median of a
      time series of image resulted in the best filtration and minimal image
      distortion. For applications where time series is impractical, adaptive
      filtration must be used to reduce image distortion. CONCLUSION: We have
      characterized the transient noise produced in CCDs by scattered radiation from a
      linac and have developed an efficient filtration scheme to remove this noise and
      restore image quality. Use of our filtration scheme allows detailed quantitative
      analysis of an image even when subjected to scattered radiation.

PMID- 28513032
TI  - COMS eye plaque brachytherapy dosimetry simulations for P103d, I125, and C131s.
AB  - Monte Carlo (MC) simulations were performed to estimate brachytherapy dose
      distributions for Collaborative Ocular Melanoma Study (COMS) eye plaques.
      Brachytherapy seed models 200, 6711, and CS-1 Rev2 carrying P103d, I125, and
      C131s radionuclides, respectively, were modeled and benchmarked against
      previously published values. Calculated dose rate constants LambdaMC were 0.684,
      0.924, and 1.052 cGy h-1 U-1 (+/-2.6%, k=1 uncertainty) for models 200, 6711, and
      CS-1 Rev2, respectively. The seeds were distributed into 10, 12, 14, 16, 18, 20,
      and 22 mm-diameter COMS eye plaques. Simulations were performed in both
      heterogeneous and homogeneous environments, where the latter were in-water and
      the former included the silastic seed carrier insert and gold-alloy plaque. MC
      based homogenous central axis dose distributions agreed within 2%+/-1% (+/-1
      s.d.) to hand-calculated values. For heterogeneous simulations, notable photon
      attenuation was observed, with dose reduction at 5 mm of 19%, 11%, and 9% for
      P103d, I125, and C131s, respectively. A depth-dependent correction factor was
      derived to correct homogenous central-axis dose distributions for plaque
      component heterogeneities, which were found to be significant at short radial
      distances.

PMID- 28513039
TI  - Sci-Thurs PM: Delivery-01: Sliding Window IMRT: Uncertainties of the leading edge
      and plateau of the beam profile.
AB  - The aim of this work is to analyze the dependence of the dose profile
      uncertainties for the sliding window IMRT (SW-IMRT) beams under the condition of
      an extreme dose rate (DR) and leaf velocity (LV). The deviations of the edges and
      plateau for the beam profiles of small number of MUs delivered using the dynamic
      MLC were studied. Field sizes with lengths of 5 and 10 cm were irradiated by
      photon beams of 2-8 MU/beam, DR = 100-600 MU/min and LS = 1-5 cm/s. Kodak TL
      radiographic films were used in the measurement. The photon beams (6 and 15 MV)
      were produced by a Varian 21EX Linac with a 120-leaf MLC. It is found that the
      MLC cannot keep the leaves moving with a proper speed continuously under a stable
      DR when beam of small MUs are irradiated. For example, the dynamic MLC needs 1.2
      s and 12 MU to irradiate a field of 5 cm length with 2 MU using DR = 600 MU/min
      and LC = 5 cm/s. The plateau of the beam profile has several sinusoidal periods
      of about 150 ms. The magnitude of the plateau uncertainties was about 7% and 15%
      for the dose of the beam with DR = 400 and 600 MU/min (2 MU/beam), respectively.
      It is concluded that SW-IMRT beams of more than 10 MUs, delivered with 1 cm/s ?
      LV ? 5 cm/s and 100 MU/min ? DR ? 600 MU/min, have a good agreement between the
      delivered and planned dose profiles.

PMID- 28513041
TI  - Erratum: "Out-of-field dose equivalents delivered by proton therapy of prostate
      cancer".

PMID- 28513050
TI  - Sci-Thurs PM: Delivery-03: Optical imaging of microscopic radiation dose
      gradients using a digital microscope.
AB  - Using superior localization and immobilization methods, stereotactic radiosurgery
      is capable of delivering spheres of dose as small as a few millimetres in
      diameter to intracranial targets. For targets abutting critical structures, the
      most conformal treatments minimize adverse radiation side effects and it is
      important, therefore, to ensure proper quality assurance prior to delivering high
      doses of radiation to eloquent brain locations in a single fraction. This work
      examines the capability of a digital microscope, with translation stage and
      associated software, to resolve dose gradients in Gafchromic EBTTM film at the
      micron level. In order to validate the microscope-film system from a radiation
      physics approach, films were irradiated to produce very steep penumbrae by using
      very small fields, lower photon energies and minimal geometric penumbra
      contribution. Orthovoltage film irradiations were done by placing films in
      phantom beneath pinhole collimators. The experimentally determined off-axis dose
      profiles were compared with Monte Carlo computer simulations which replicated the
      irradiation geometry and served to validate our measured data. The measured 80% -
      20% penumbral widths were 46 MUm +/- 26 MUm (100 kVp, 2 mm field size) and 69 MUm
      +/- 27 MUm (300 kVp, 2 mm field size). In the energy range covered, the measured
      penumbral widths agreed with Monte Carlo computer simulations within experimental
      uncertainty. The effects of noise originating from both the film and the
      microscope system are discussed and improvements to this system suggested.

PMID- 28513052
TI  - Primary care and cancer: Facing the challenge of early diagnosis and
      survivorship.
AB  - With ageing populations and an increasing lifetime risk of cancer, primary care
      will continue to play an increasingly important role in early diagnosis and
      cancer survivorship, especially with the lowering of risk thresholds for referral
      and diagnostic investigations. However, primary care in many countries is in
      crisis with increasing workloads for primary care physicians. Potential solutions
      to these challenges will be outlined including development of multidisciplinary
      teams, diagnostic decision support, increasing access to diagnostics and cost
      effective referral pathways.

PMID- 28513053
TI  - High-frequency ultrasound quantification of acute radiation dermatitis: pilot
      study of patients undergoing radiotherapy for breast cancer.
AB  - BACKGROUND: Acute radiation dermatitis (ARD) is a frequent complication after
      breast cancer radiotherapy and is usually assessed by semi-quantitative clinical
      scores, which may be subject to inter-observer variability. High-frequency
      ultrasound imaging of the skin can reliably quantify thickness and edema in
      diseased skin. We aimed to compare the relative increase in dermal thickness of
      the irradiated zone in breast-cancer patients undergoing radiotherapy, with
      clinical severity. METHODS: A consecutive series of patients undergoing treatment
      for breast cancer by lumpectomy and radiotherapy in a 6-month period also
      underwent clinical and ultrasound evaluation of ARD. RESULTS: We included 34
      female patients 17 had grade 1 (group 1), 17 had grade 2 or grade 3 ARD (group
      2). The mean relative increase in dermal thickness in irradiated skin (RIDTIS)
      was greater for group 2 than 1: 0.53 vs 0.29 mm (P=.023). On univariate analysis,
      ARD was associated with skin phototype, breast volume and RIDTIS, and on
      multivariable analysis, breast volume and age remained predictive of the disease.
      CONCLUSION: Patients with more severe dermatitis showed significantly increased
      dermal thickness. Dermal thickness is a quantitative variable that could help
      quantify the efficacy of drugs and improve the treatment of this disease in
      patients undergoing radiotherapy.

PMID- 28513054
TI  - Is there a common motor dysregulation in sleepwalking and REM sleep behaviour
      disorder?
AB  - This study sought to determine if there is any overlap between the two major non
      rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep
      terrors and rapid eye movement sleep behaviour disorder. We assessed adult
      patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour
      disorder screening questionnaires and determined if they had enhanced muscle tone
      during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep
      behaviour disorder patients using the Paris Arousal Disorders Severity Scale and
      determined if they had more N3 awakenings. The 251 participants included 64
      patients with rapid eye movement sleep behaviour disorder (29 with idiopathic
      rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep
      behaviour disorder associated with Parkinson's disease), 62 patients with
      sleepwalking/sleep terrors, 66 old healthy controls (age-matched with the rapid
      eye movement sleep behaviour disorder group) and 59 young healthy controls (age
      matched with the sleepwalking/sleep terrors group). They completed the rapid eye
      movement sleep behaviour disorder screening questionnaire, rapid eye movement
      sleep behaviour disorder single question and Paris Arousal Disorders Severity
      Scale. In addition, all the participants underwent a video-polysomnography. The
      sleepwalking/sleep terrors patients scored positive on rapid eye movement sleep
      behaviour disorder scales and had a higher percentage of 'any' phasic rapid eye
      movement sleep without atonia when compared with controls; however, these
      patients did not have higher tonic rapid eye movement sleep without atonia or
      complex behaviours during rapid eye movement sleep. Patients with rapid eye
      movement sleep behaviour disorder had moderately elevated scores on the Paris
      Arousal Disorders Severity Scale but did not exhibit more N3 arousals (suggestive
      of non-rapid eye movement parasomnia) than the control group. These results
      indicate that dream-enacting behaviours (assessed by rapid eye movement sleep
      behaviour disorder screening questionnaires) are commonly reported by
      sleepwalking/sleep terrors patients, thus decreasing the questionnaire's
      specificity. Furthermore, sleepwalking/sleep terrors patients have excessive
      twitching during rapid eye movement sleep, which may result either from a higher
      dreaming activity in rapid eye movement sleep or from a more generalised non
      rapid eye movement/rapid eye movement motor dyscontrol during sleep.

PMID- 28513055
TI  - Breastfeeding in the context of domestic violence-a cross-sectional study.
AB  - AIMS: To determine the differences in breastfeeding among women who did and did
      not experience domestic violence during pregnancy and postpartum in a Swedish
      context. In addition, to identify possible differences regarding breastfeeding
      between groups with or without a history of violence. Further, determine the
      relationship between exclusive breastfeeding and symptoms of depression.
      BACKGROUND: History of violence may increase the risk of depression and a
      decrease in, or cessation of, breastfeeding. DESIGN: The study has a cross
      sectional design. METHODS: Data were collected prospectively from March 2012 -
      May 2015. A cohort of 731 mothers answered a questionnaire from a larger project
      (1.5 years postpartum). RESULTS: Breastfeeding was reported by 93.7% of
      participants. Women exposed to domestic violence during pregnancy and/or
      postpartum (4.5%) were just as likely to breastfeed as women who had not reported
      exposure to domestic violence. There were no statistically significant
      differences between the groups with or without a history of violence regarding
      exclusive breastfeeding. Women reporting several symptoms of depression breastfed
      exclusively to a lesser extent compared with women who had a few symptoms of
      depression. CONCLUSION: Domestic violence did not influence breastfeeding
      prevalence or duration. Breastfeeding did not differ in women with or without a
      history of violence. Symptoms of depression influenced duration of exclusive
      breastfeeding. Beyond recognizing women who are exposed to violence, it is
      important to identify and to support pregnant women and new mothers with symptoms
      of depression as their health and the health of their infants depends on the
      mothers' mental well-being.

PMID- 28513056
TI  - Lessons learned from a pilot study of an Indigenous patient navigator
      intervention in Queensland, Australia.
AB  - Indigenous patient navigator (IPN) programmes show promise in addressing barriers
      to cancer care and facilitation of patient self-efficacy. The purpose of this
      paper is to describe and reflect upon the experience of training an IPN and
      implementation of the intervention in the Australian context with Indigenous
      cancer patients. Randomised clinical trial might provide the best available
      evaluation measure of an intervention but caution should be taken in the
      implementation process. Socio-cultural aspects and training can affect the
      conduct of this type of intervention. We report here five issues needing
      consideration prior to implementing such intervention. Specifically: (1)
      recognition of the collective bonds within Indigenous community and understanding
      by IPN of the degree of personal assistance perceived as not intrusive by the
      patient; (2) conduct ongoing evaluation of the different role of an IPN involved
      in this intervention care provider vs. researcher. (3) meaningful engagement
      develops from a trusting/collaborative relationship between research team and
      study site staff which may not occur in the study time frame; (4) existing skills
      as well as training provided may not translate in the IPN understanding and
      aligning with the study objectives/research values; (5) recruitment of
      participants requires innovative and highly flexible strategies to be successful.

PMID- 28513057
TI  - Systemic inflammation and alterations to cerebral blood flow in obstructive sleep
      apnea.
AB  - Systemic inflammation and alterations to regional cerebral blood flow (CBF) have
      been reported previously in obstructive sleep apnea (OSA). This study utilized
      arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI) to
      evaluate CBF in OSA patients and determine its relationship with systemic
      inflammation. Twenty male patients with moderate and severe OSA [apnea-hypopnea
      index (AHI) >15] and 16 healthy male volunteers (AHI <5) were recruited. Early-
      or late-phase changes in leucocyte apoptosis and its subsets were determined by
      flow cytometry. Perfusion MRI data were acquired with a pulsed continuous ASL
      technique. The CBF maps were compared using voxel-based statistics to determine
      differences between the OSA and control groups. The differences in CBF, clinical
      severity and leucocyte apoptosis were correlated. Exploratory groupwise
      comparison between the two groups revealed that the OSA patients exhibited low
      CBF values in the vulnerable regions. The lower regional CBF values were
      correlated with higher clinical disease severity and leucocyte apoptosis. OSA
      impairs cerebral perfusion in vulnerable regions, and this deficit is associated
      with increased disease severity. The apparent correlation between systemic
      inflammation and cerebral perfusion may be indicative of haemodynamic alterations
      and their consequences in OSA.

PMID- 28513058
TI  - Pro-myogenic and low-oxygen culture increases expression of contractile smooth
      muscle markers in human fibroblasts.
AB  - Smooth muscle cells (SMCs) are essential for tissue engineering strategies to
      fabricate organs such as blood vessels, the oesophagus and bladder, and to create
      disease models of these systems. In order for such therapies and models to be
      feasible, SMCs must be sourced effectively to enable production of large numbers
      of functional cells. In vitro, SMCs divide slowly and demonstrate short
      proliferative lifespans compared with other types of cells, including stem cells
      and fibroblasts, limiting the number of cells that can be derived from expansion
      in culture of a primary isolation. As such, it would be beneficial to better
      understand the factors underlying induction and maintenance of SMC phenotypes, in
      order to produce new sources of SMCs for tissue engineering and disease
      modelling. Here we report the ability of human dermal fibroblasts to display
      patterns of gene expression resembling contractile SMCs when cultured under
      conditions that are known to promote a contractile phenotype in SMCs, including
      culture on collagen IV, low-serum culture, TGF-beta1 treatment and hypoxia. These
      factors drive expression of the myogenic transcription factor myocardin, as well
      as expression of several of its gene targets that are known contributors to
      contractile phenotype in SMCs, including smooth muscle alpha actin, calponin, and
      myosin heavy chain. Our results suggest that culture conditions associated with
      culture of SMCs may be sufficient to induce myogenic gene expression patterns and
      potential myogenic function in non-muscle cells.

PMID- 28513060
TI  - Increased oral inflammation, leukocytes, and leptin, and lower adiponectin in
      overweight or obesity.
AB  - OBJECTIVES: The association between body mass index (BMI) and oral diseases was
      investigated, and levels of obesity-related inflammatory mediators were
      evaluated. SUBJECTS AND METHODS: Participants (n = 160) were clinically and
      radiographically examined for oral diseases. Blood profiles were recorded. Levels
      of adiponectin, leptin, and C-reactive protein (CRP) were measured. RESULTS: One
      hundred and thirteen (70.6%) participants had overweight or obese status (BMI >=
      23.0 kg/m2 ). Sum of dental diseases and severe periodontitis were higher in
      overweight or obese individuals than in normal-weight participants (p = .037 and
      p = .002, respectively). A significant difference in oral mucosal disorders
      between normal weight and overweight or obesity was not found. Plasma leukocyte
      counts, liver enzymes, leptin, and CRP levels were increased while adiponectin
      levels were decreased in individuals with BMI>=23.0 kg/m2 compared with normal
      weight participants. After adjusting for age, sex, fasting plasma glucose level,
      smoking, and exercise, obesity was associated with sum of dental diseases (beta =
      0.239, p = .013), severe periodontitis (OR=4.52; 95% CI 1.37, 14.95, p = .013),
      adiponectin (beta = -0.359, p < .001), leptin (beta = 0.630, p < .001), and CRP
      levels (OR=12.66; 95% CI 3.07, 52.21, p < .001). CONCLUSION: Overweight or obese
      Thai people were related to an increase in inflammatory dental and periodontal
      diseases with an altered health profile and plasma inflammatory mediators.

PMID- 28513061
TI  - Disorder-specific versus generic cognitive-behavioral treatment of anxiety
      disorders in children and young people: a systematic narrative review of evidence
      for the effectiveness of disorder-specific CBT compared with the disorder-generic
      treatment, Coping Cat.
AB  - BACKGROUND: Coping Cat (CC), a generic cognitive-behavioral intervention for
      anxiety disorders in children and young people, is recommended in the United
      Kingdom for social anxiety disorder (SAD), generalized anxiety disorder,
      separation anxiety (SA), and specific phobias (SP), with disorder-specific
      approaches generally favored in treatment of anxiety disorders in adults.
      OBJECTIVES: To compare CC with disorder-specific cognitive-behavioral therapy
      (CBT) interventions based on anxiety-related treatment outcomes. STUDY SELECTION:
      Primary research articles describing treatment of children and young people aged
      7-17 for SAD, generalized anxiety disorder, SA, and SP, using CC or disorder
      specific CBT. RESULTS: Ten studies implemented CC and four implemented disorder
      specific CBT. One study compared CC with a disorder-specific approach. There was
      a lack of data to support use of CC in treatment of SPs. However, CC was equally
      effective as disorder-specific treatments for SA and SAD. CONCLUSIONS: A lack of
      data exists for disorder-specific CBT interventions compared to CC.

PMID- 28513059
TI  - Fluoxetine and congenital malformations: a systematic review and meta-analysis of
      cohort studies.
AB  - AIMS: To investigate the safety of fluoxetine use during pregnancy, and to better
      understand the relationship between maternal fluoxetine use during the first
      trimester and congenital malformations in infants. METHODS: PubMed and Web of
      Science databases were systematically searched from inception to 21 March 2016.
      Additional studies were identified in a manual search of the reference lists. Two
      reviewers independently extracted data. A third reviewer checked the data.
      Estimates were pooled using a random-effects model to calculate the summarized
      relative ratios (RR) and 95% confidence intervals (CI). RESULTS: Among 1918
      initially identified articles, 16 cohort studies were included. The offspring of
      pregnant women exposed to fluoxetine during the first trimester had a
      statistically increased risk of major malformations (RR = 1.18, 95% CI = 1.08
      1.29), cardiovascular malformations (RR = 1.36, 95% CI = 1.17-1.59), septal
      defects (RR = 1.38, 95% CI = 1.19-1.61), and non-septal defects (RR = 1.39, 95%
      CI = 1.12-1.73) with low heterogeneity in infants. There were no significant
      observations of other system-specific malformations in the nervous system, eye,
      urogenital system, digestive system, respiratory system, or musculoskeletal
      system, respectively. There was no indication of publication bias. CONCLUSIONS:
      The results of this meta-analysis indicate maternal fluoxetine use is associated
      with a slightly increased risk of cardiovascular malformations in infants. Health
      care providers and pregnant women must weigh the risk-benefit potential of these
      drugs when making decisions about whether to treat with fluoxetine during
      pregnancy.

PMID- 28513063
TI  - Challenges and opportunities for addressing adolescent cyberbullying within the
      context of clinically meaningful psychological outcomes.

PMID- 28513062
TI  - What are the family needs when a parent has mental health problems? Evidence from
      a systematic literature review.
AB  - PROBLEM: Little evidence exists showing how a given high-risk group of children
      born to parents with poor mental health seek help and how care may be improved in
      order to better reach and support their families. METHODS: A systematic
      literature review was undertaken to identify the needs and help-seeking behaviors
      of children and their parents. Through an analysis of both quantitative and
      qualitative studies, published in German- and English-speaking research
      literature, the needs of children and parents were identified and categorized.
      Findings concerning their help-seeking behavior and the influence of demographic
      variables on needs and help-seeking behaviors were also described. FINDINGS: In
      the primary studies, the most identified parental needs were "the need for being
      a good parent"; "worries about the child's well-being"; and "the need for
      practical help." For children, the categories identified included "the need for
      knowledge"; "worries about parent's well-being"; and "the need for normality."
      However, information about help-seeking behaviors and influences of demographic
      factors was fairly limited in the literature. CONCLUSIONS: In families with
      parental mental health problems, it seems especially important to take a family
      focused approach. The individual needs of children (and their families) should
      shape the planning of treatment and nursing care.

PMID- 28513065
TI  - Catalyst-Controlled Regiodivergent Alkyne Insertion in the Context of C-H
      Activation and Diels-Alder Reactions: Synthesis of Fused and Bridged Cycles.
AB  - Rhodium(III)- and cobalt(III)-catalyzed C-H activation of indoles and coupling
      with 1,6-enynes is discussed. Under rhodium(III) catalysis, the alkyne insertion
      follows 2,1-regioselectivity with a subsequent type-I intramolecular Diels-Alder
      reaction (IMDA) to afford [6,5]-fused cycles. When catalyzed by the cobalt(III)
      congener, 1,2-insertion of the alkyne is preferred, and followed by a rare type
      II IMDA, thus leading to bridged [3,3,1]-cycles. This selectivity of the alkyne
      insertion was mainly tuned by the steric sensitivity of the catalyst.

PMID- 28513064
TI  - Autofluorescence of collagen fibres in scar.
AB  - BACKGROUND/PURPOSE: Autofluorescence has become an important factor associated
      with diagnosis and treatment of many diseases. METHODS: Full thickness skin
      grafts and scar biopsies were obtained from five volunteers. The normal skin or
      scar tissue paraffin-wax sections were stained with HE and the autofluorescence
      of collagen fibres was viewed under fluorescence microscopy. RESULTS: In normal
      skin, the autofluorescence was showed in dermis, specifically in collagen fibres.
      There was very weak autofluorescence in epidermis. The spectrum was excited at
      488 nm and the peak value of autofluorescence was significantly different between
      reticular layer (169.24+/-9.18) and papillar layer of dermis (103.91+/-15.23). In
      scar tissue, the autofluorescence was showed in collagen fibres and the peak
      value was 176.71+/-20.69. The structure of collagen fibres in normal skin or scar
      tissue was different in loose degree, thickness, boundle size, and morphology by
      their autofluorescence. CONCLUSION: The different peak value of autofluorescence
      between scar and normal skin may due to the different density of collagen fibtes
      in them. This study may provide us a simple and effective assessment indicator
      and method for diagnosis and treatment of scar.

PMID- 28513066
TI  - Sexual selection, speciation and constraints on geographical range overlap in
      birds.
AB  - The role of sexual selection as a driver of speciation remains unresolved, not
      least because we lack a clear empirical understanding of its influence on
      different phases of the speciation process. Here, using data from 1306 recent
      avian speciation events, we show that plumage dichromatism (a proxy for sexual
      selection) does not predict diversification rates, but instead explains the rate
      at which young lineages achieve geographical range overlap. Importantly, this
      effect is only significant when range overlap is narrow (< 20%). These findings
      are consistent with a 'differential fusion' model wherein sexual selection
      reduces rates of fusion among lineages undergoing secondary contact, facilitating
      parapatry or limited co-existence, whereas more extensive sympatry is contingent
      on additional factors such as ecological differentiation. Our results provide a
      more mechanistic explanation for why sexual selection appears to drive early
      stages of speciation while playing a seemingly limited role in determining broad
      scale patterns of diversification.

PMID- 28513067
TI  - Interventions for cutaneous molluscum contagiosum.
AB  - BACKGROUND: Molluscum contagiosum is a common skin infection that is caused by a
      pox virus and occurs mainly in children. The infection usually resolves within
      months in people without immune deficiency, but treatment may be preferred for
      social and cosmetic reasons or to avoid spreading the infection. A clear evidence
      base supporting the various treatments is lacking.This is an update of a Cochrane
      Review first published in 2006, and updated previously in 2009. OBJECTIVES: To
      assess the effects of specific treatments and management strategies, including
      waiting for natural resolution, for cutaneous, non-genital molluscum contagiosum
      in people without immune deficiency. SEARCH METHODS: We updated our searches of
      the following databases to July 2016: the Cochrane Skin Group Specialised
      Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched six trial registers
      and checked the reference lists of included studies and review articles for
      further references to relevant randomised controlled trials. We contacted
      pharmaceutical companies and experts in the field to identify further relevant
      randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials of
      any treatment of molluscum contagiosum in people without immune deficiency. We
      excluded trials on sexually transmitted molluscum contagiosum and in people with
      immune deficiency (including those with HIV infection). DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected studies, assessed
      methodological quality, and extracted data from selected studies. We obtained
      missing data from study authors where possible. MAIN RESULTS: We found 11 new
      studies for this update, resulting in 22 included studies with a total of 1650
      participants. The studies examined the effects of topical (20 studies) and
      systemic interventions (2 studies).Among the new included studies were the full
      trial reports of three large unpublished studies, brought to our attention by an
      expert in the field. They all provided moderate-quality evidence for a lack of
      effect of 5% imiquimod compared to vehicle (placebo) on short-term clinical cure
      (4 studies, 850 participants, 12 weeks after start of treatment, risk ratio (RR)
      1.33, 95% confidence interval (CI) 0.92 to 1.93), medium-term clinical cure (2
      studies, 702 participants, 18 weeks after start of treatment, RR 0.88, 95% CI
      0.67 to 1.14), and long-term clinical cure (2 studies, 702 participants, 28 weeks
      after start of treatment, RR 0.97, 95% CI 0.79 to 1.17). We found similar but
      more certain results for short-term improvement (4 studies, 850 participants, 12
      weeks after start of treatment, RR 1.14, 95% CI 0.89 to 1.47; high-quality
      evidence). For the outcome 'any adverse effect', we found high-quality evidence
      for little or no difference between topical 5% imiquimod and vehicle (3 studies,
      827 participants, RR 0.97, 95% CI 0.88 to 1.07), but application site reactions
      were more frequent in the groups treated with imiquimod (moderate-quality
      evidence): any application site reaction (3 studies, 827 participants, RR 1.41,
      95% CI 1.13 to 1.77, the number needed to treat for an additional harmful outcome
      (NNTH) was 11); severe application site reaction (3 studies, 827 participants, RR
      4.33, 95% CI 1.16 to 16.19, NNTH over 40).For the following 11 comparisons, there
      was limited evidence to show which treatment was superior in achieving short-term
      clinical cure (low-quality evidence): 5% imiquimod less effective than cryospray
      (1 study, 74 participants, RR 0.60, 95% CI 0.46 to 0.78) and 10% potassium
      hydroxide (2 studies, 67 participants, RR 0.65, 95% CI 0.46 to 0.93); 10%
      Australian lemon myrtle oil more effective than olive oil (1 study, 31
      participants, RR 17.88, 95% CI 1.13 to 282.72); 10% benzoyl peroxide cream more
      effective than 0.05% tretinoin (1 study, 30 participants, RR 2.20, 95% CI 1.01 to
      4.79); 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5%
      salicylic acid alone (1 study, 30 participants, RR 3.50, 95% CI 1.23 to 9.92);
      and iodine plus tea tree oil more effective than tea tree oil (1 study, 37
      participants, RR 0.20, 95% CI 0.07 to 0.57) or iodine alone (1 study, 37
      participants, RR 0.07, 95% CI 0.01 to 0.50). Although there is some uncertainty,
      10% potassium hydroxide appears to be more effective than saline (1 study, 20
      participants, RR 3.50, 95% CI 0.95 to 12.90); homeopathic calcarea carbonica
      appears to be more effective than placebo (1 study, 20 participants, RR 5.57, 95%
      CI 0.93 to 33.54); 2.5% appears to be less effective than 5% solution of
      potassium hydroxide (1 study, 25 participants, RR 0.35, 95% CI 0.12 to 1.01); and
      10% povidone iodine solution plus 50% salicylic acid plaster appears to be more
      effective than salicylic acid plaster alone (1 study, 30 participants, RR 1.43,
      95% CI 0.95 to 2.16).We found no statistically significant differences for other
      comparisons (most of which addressed two different topical treatments). We found
      no randomised controlled trial evidence for expressing lesions or topical
      hydrogen peroxide.Study limitations included no blinding, many dropouts, and no
      intention-to-treat analysis. Except for the severe application site reactions of
      imiquimod, none of the evaluated treatments described above were associated with
      serious adverse effects (low-quality evidence). Among the most common adverse
      events were pain during application, erythema, and itching. Included studies of
      the following comparisons did not report adverse effects: calcarea carbonica
      versus placebo, 10% povidone iodine plus 50% salicylic acid plaster versus
      salicylic acid plaster, and 10% benzoyl peroxide versus 0.05% tretinoin.We were
      unable to judge the risk of bias in most studies due to insufficient information,
      especially regarding concealment of allocation and possible selective reporting.
      We considered five studies to be at low risk of bias. AUTHORS' CONCLUSIONS: No
      single intervention has been shown to be convincingly effective in the treatment
      of molluscum contagiosum. We found moderate-quality evidence that topical 5%
      imiquimod was no more effective than vehicle in terms of clinical cure, but led
      to more application site reactions, and high-quality evidence that there was no
      difference between the treatments in terms of short-term improvement. However,
      high-quality evidence showed a similar number of general side effects in both
      groups. As the evidence found did not favour any one treatment, the natural
      resolution of molluscum contagiosum remains a strong method for dealing with the
      condition.

PMID- 28513069
TI  - Predict pancreatic fistula after pancreaticoduodenectomy: ratio body
      thickness/main duct.
AB  - BACKGROUND: The occurrence of post-operative pancreatic fistula (POPF) after
      pancreaticoduodenectomy is a challenging issue. The aim was to identify variables
      on preoperative computed tomography (CT) scan, useful to predict clinically
      significant POPF (grades B-C) after pancreaticoduodenectomy. METHODS: Patients
      presented POPF after pancreaticoduodenectomy were included from two tertiary
      referral centres. B/W ratio was defined by ratio of pancreas body thickness (B)
      to main pancreatic duct (W). The predictive parameters of POPF on CT scan were
      assessed with a receiving operator characteristics (ROC) curve and intrinsic
      characteristics. RESULTS: Between 2010 and 2013, 186 patients who underwent
      pancreaticoduodenectomy were included. POPF occurred in 25% of them, and was
      clinically significant in 13%. After univariate analysis, endocrine tumours (P =
      0.03), main pancreatic duct size (P < 0.01) and B/W ratio (P = 0.04) were
      significantly associated with POPF. ROC curve showed a greater area under curve
      for B/W ratio (0.68) than for main pancreatic duct size (0.33). A 3.8 threshold
      displayed 80 and 51% for sensibility and specificity, respectively, and a
      negative predictive value of 94%. A B/W ratio >3.8 increased the rates of post
      operative haemorrhage (odds ratio = 4.3 (1.4-13.2), P = 0.01), and reintervention
      (odds ratio = 3.4 (1.2-9.6), P = 0.02). CONCLUSIONS: B/W ratio superior to 3.8
      assessed on preoperative CT scan may be an easy tool to predict clinically
      significant POPF after pancreaticoduodenectomy.

PMID- 28513068
TI  - A randomized controlled trial: branched-chain amino acid levels and glucose
      metabolism in patients with obesity and sleep apnea.
AB  - There is evidence that changes in branched-chain amino acid (BCAA) levels may
      correlate with the efficacy of therapeutic interventions for affecting
      improvement in metabolic control. The objective of this study was to evaluate
      whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate
      in insulin sensitivity and glucose tolerance after continuous positive airway
      pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A
      prospective randomized controlled trial of OSA patients with morbid obesity was
      conducted. Eighty patients were randomized into two groups: 38 received
      conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels
      of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and
      after treatment. After treatment, significant decreases of leucine levels were
      observed in both groups when compared with baseline levels (P < 0.005). With
      respect to patients with normal glucose tolerance (NGT), patients with impaired
      glucose tolerance (IGT) had higher baseline levels of isoleucine (78 +/- 16
      versus 70 +/- 13 MUmol L-1 , P = 0.014) and valine (286 +/- 36 versus 268 +/- 41
      MUmol L-1 , P = 0.049), respectively. Changes in levels of leucine and isoleucine
      after treatment were related negatively to changes in fasting plasma glucose and
      glycosylated haemoglobin values only in the conservative group (P < 0.05). In
      summary, we found that the treatment with CPAP for 12 weeks caused similar
      changes in circulating BCAAs concentrations to conservative treatment and a
      differential metabolic response of CPAP and conservative treatment was observed
      between the relationship of BCAAs and glucose homeostasis. Additional studies are
      needed to determine the interplay between branched-chain amino acids and glucose
      metabolism in patients with sleep apnea.

PMID- 28513070
TI  - Influence of quercetin on the interaction of gliclazide with human serum albumin 
      spectroscopic and docking approaches.
AB  - Protein-binding interactions are displacement reactions which have been
      implicated as the causative mechanisms in many drug-drug interactions. Thus, the
      aim of presented study was to analyse human serum albumin-binding displacement
      interaction between two ligands, hypoglycaemic drug gliclazide and widely
      distributed plant flavonoid quercetin. Fluorescence analysis was used in order to
      investigate the effect of substances on intrinsic fluorescence of human serum
      albumin (HSA) and to define binding and quenching properties of ligand-albumin
      complexes in binary and ternary systems, respectively. Both ligands showed the
      ability to bind to HSA, although to a different extent. The displacement effect
      of one ligand from HSA by the other one has been described on the basis of the
      quenching curves and binding constants comparison for the binary and ternary
      systems. According to the fluorescence data analysis, gliclazide presents a
      substance with a lower binding capacity towards HSA compared with quercetin.
      Results also showed that the presence of quercetin hindered the interaction
      between HSA and gliclazide, as the binding constant for gliclazide in the ternary
      system was remarkably lower compared with the binary system. This finding
      indicates a possibility for an increase in the non-bound fraction of gliclazide
      which can lead to its more significant hypoglycaemic effect. Additionally,
      secondary and tertiary structure conformational alterations of HSA upon binding
      of both ligands were investigated using synchronous fluorescence, circular
      dichroism and FT-IR. Experimental data were complemented with molecular docking
      studies. Obtained results provide beneficial information about possible
      interference upon simultaneous co-administration of the food/dietary supplement
      and drug.

PMID- 28513071
TI  - Juvenile idiopathic arthritis in multiplex families: longitudinal follow-up.
AB  - OBJECTIVE: To describe the physical, social, educational and employment status
      and clinical outcomes of patients with juvenile idiopathic arthritis (JIA) from
      multiplex families. METHODS: All familial JIA patients were treated and had
      regular follow-up between 1990 and 2015 at King Faisal Specialist Hospital and
      Research Center (KFSH-RC), Riyadh, were included. Demographic data, disease
      duration, active arthritis and articular and extra-articular damage at last
      follow-up visit were reviewed. Additionally, social, educational and employment
      history were obtained via personal or phone interviews. RESULTS: Twenty-three
      patients (20 females) belonging to 10 families were included. The mean age was
      14.6 (+/-9) years with mean disease duration of 11.4 (+/-9) years and mean follow
      up duration of 10.5 (+/-6). Fourteen patients had systemic JIA while eight
      patients had polyarticular subtype, and one patient had psoriatic arthritis. All
      patients received concomitant treatment. Twenty-one patients commenced biologic
      agents; treatment switched to another agent in all of them because of inadequate
      response. Most patients had progressive disease course. Twelve patients had
      active polyarthritis and 22 patients showed evidence of articular damage. All
      patients had raised inflammatory markers. Eighteen patients had short stature and
      11 patients had delayed puberty. Two patients had lower limb lymphedema and one
      patient had a single kidney with refractory hypertension. Three patients
      underwent hip arthroplasty. Seventeen patients had satisfactory educational
      achievement and four patients were in employment. Two patients died due to
      infection. CONCLUSION: Our results showed the largest familial clusters of JIA in
      the Middle East. Patients with familial JIA had refractory disease with
      progressive disease course.

PMID- 28513072
TI  - Self-Assembly and Local Manipulation of Au-Pyridyl Coordination Networks on Metal
      Surfaces.
AB  - Using scanning tunnelling microscopy (STM), we demonstrate that Au-pyridyl
      coordination can be used to assemble two-dimensional coordination network
      structures on metal surfaces. The polymorphism of the coordination network
      structures can be manipulated at both the micro- and nanoscale. Using the same
      organic ligand, we assembled two distinct polymorphic network structures, which
      were assisted by threefold Au-pyridyl coordination on Ag(111) with predeposited
      Au atoms (alpha-network), and by twofold Au-pyridyl coordination on Au(111) (beta
      network), respectively. Specifically on the Au(111) surface, single-oriented beta
      network domains as large as ~400 nm were selected by thermal annealing. We
      ascribe this global control strategy to distinct Au bonding modes tuned by
      molecule-substrate interactions. Using an STM tip, we succeeded in creating alpha
      network domains (~10 nm) locally within the homogeneous beta-network domain areas
      on Au(111) in a controlled manner.

PMID- 28513073
TI  - Early neurocognitive improvements following parathyroidectomy for primary
      hyperparathyroidism.
AB  - OBJECTIVES: To establish a time frame for postoperative improvements in
      neurocognitive function in patients who undergo parathyroidectomy for primary
      hyperparathyroidism by utilizing repeat neuropsychological assessment at multiple
      time points before and after surgery. STUDY DESIGN: Prospective cohort study.
      METHODS: A prospective study was conducted at a tertiary academic medical center
      between August 2014 and December 2015, including 50 patients with primary
      hyperparathyroidism who underwent parathyroidectomy. A panel of neurocognitive
      tests was administered at two separate time points: preoperative and 1-week
      postoperative. Validated neuropsychological assessment tools were utilized,
      including Rey Auditory-Verbal Learning Test, Trail Making Test A and B, Benton
      Controlled Oral Word Association, WAIS-IV Digit Span, Hospital Anxiety and
      Depression Scale, Positive and Negative Affect Schedule, and Insomnia Severity
      Index. Barona Information Sheet was used to collect demographic data. Paired t
      tests were to compare pre- and postoperative scores. RESULTS: Thirty-five
      patients completed the preoperative and 1-week postoperative testing. In
      cognitive testing, significant improvement was noted in immediate recall (P <
      0.001), working memory (P = 0.011), and attention (P = 0.008) at 1-week
      postoperative. In mood testing, depression (P < 0.001), anxiety (P < 0.001), and
      negative affect (P = 0.001) scores were significantly improved at 1-week
      postoperative. Insomnia scores also were significantly improved at 1 week (P <
      0.001). CONCLUSION: Objective improvements in neurocognitive function following
      parathyroidectomy for primary hyperparathyroidism were noted as early as 1 week
      after surgery, which is earlier than previously reported. LEVEL OF EVIDENCE: 2b.
      Laryngoscope, 128:775-780, 2018.

PMID- 28513074
TI  - Delta-Myrtoxin-Mp1a is a Helical Heterodimer from the Venom of the Jack Jumper
      Ant that has Antimicrobial, Membrane-Disrupting, and Nociceptive Activities.
AB  - Delta-Myrtoxin-Mp1a (Mp1a), a 49-residue heterodimeric peptide from the venom of
      Myrmecia pilosula, comprises a 26-mer A chain and a 23-mer B chain connected by
      two disulfide bonds in an antiparallel arrangement. Combination of the individual
      synthetic chains through aerial oxidation remarkably resulted in the self
      assembly of Mp1a as a homogenous product without the need for directed disulfide
      bond formation. NMR analysis revealed a well-defined, unique structure containing
      an antiparallel alpha-helix pair. Dual polarization interferometry (DPI) analysis
      showed strong interaction with supported lipid bilayers and insertion within the
      bilayers. Mp1a caused non-specific Ca2+ influx in SH-SY5Y cells with a half
      maximal effective concentration (EC50 ) of 4.3 MUm. Mp1a also displayed broad
      spectrum antimicrobial activity, with the highest potency against Gram-negative
      Acinetobacter baumannii (MIC 25 nm). Intraplantar injection (10 MUm) in mice
      elicited spontaneous pain and mechanical allodynia. Single- and two-chain
      mimetics of Mp1a revealed functional selectivity.

PMID- 28513075
TI  - Using interpretation services during clerkships.
AB  - BACKGROUND: Although using professional interpreters is known to improve health
      outcomes for patients when language barriers are present, care providers often
      hesitate to use them. Training in how to use interpreters has been effective in
      increasing students' knowledge and self-efficacy, but little is known about how
      students apply the competencies gained. We explored students' perspectives on how
      they dealt with language barriers during their clerkships. METHOD: Students in
      the Netherlands who received training (n = 8) and who did not receive training (n
      = 8) were interviewed about their experiences during their clerkships with
      regards to language barriers and the use of professional interpreters. RESULTS:
      Students do not report using interpretation services during clerkships, even when
      they have been trained. Students report that their supervisors and other staff
      members provide barriers to the use of interpretation services. CONCLUSIONS: Not
      only students but also staff need training in the use of professional
      interpretation services, because staff serve as role models for the students.
      Care providers often hesitate to use [professional interpreters].

PMID- 28513077
TI  - Tuneable luminescence properties of EDTA-assisted ZnS:Mn nanocrystals from a
      yellow-orange to a red emission band.
AB  - Luminescence technology has been improved with the help of semiconductor
      nanoparticles that possess novel optical and electrical properties compared with
      their bulk counterpart. The aim of this study was to design semiconductor
      nanocrystals in their pure (ZnS) or doped form (ZnS:Mn) with different
      concentrations of Mn2+ ions by a wet chemical route stabilized by ethylenediamine
      tetra-acetic acid (EDTA) and to evaluate their luminescence properties. The
      nanocrystals were characterized by physicochemical techniques such as X-ray
      diffraction (XRD), High-resolution transmission electron microscopy (HRTEM),
      selected area electron diffraction (SEAD), EDS, and ultraviolet (UV)-visible
      light and photoluminescence (PL) studies. These results showed the presence of
      cubic phase and spherically shaped nanocrystals. A blue shift with respect to
      their bulk counterpart was observed. PL emission spectra were observed with a
      fixed blue peak and the yellow-orange bands were red shifted towards the red
      region under the same excitation wavelength. The orange-red bands were attributed
      to the radiation transition of electrons in 3d5 unfilled shells of Mn2+ ions [4
      T1 (4 G)-6 A1 (6 S)]; the ZnS matrix varied with Mn2+ concentration. Shift and
      increase in the intensity of the PL and absorption bands were observed with
      increase in Mn content. The study showed that Mn2+ -doped ZnS nanocrystal
      emission bands can be tuned from the yellow-orange to the red regions under a
      controlled synthesis process and could be used as promising luminescent emitters
      in the biology field upon functionalization with suitable materials. Further
      studies on construction with various other materials will be useful for practical
      applications.

PMID- 28513078
TI  - Peripheral synucleinopathy in early Parkinson's disease: Submandibular gland
      needle biopsy findings.

PMID- 28513076
TI  - A computational assessment of the predicted structures of Human Macrophage
      Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human
      CD74 receptor.
AB  - The human macrophage migration inhibitory factor 1 (Hu-MIF-1) is a protein
      involved in the inflammatory and immunology response to parasite infection. In
      the present study, the existence of Hu-MIF-1 from parasites have been explored by
      mining WormBase. A total of 35 helminths were found to have Hu-MIF-1 homologs,
      including some parasites of importance for public health. Physicochemical,
      structural, and biological properties of Hu-MIF-1 were compared with its
      orthologs in parasites showing that most of these are secretory proteins, with
      positive net charge and presence of the Cys-Xaa-Xaa-Cys motif that is critical
      for its oxidoreductase activity. The inhibitor-binding site present in Hu-MIF-1
      is well conserved among parasite MIFs suggesting that Hu-MIF inhibitors may
      target orthologs in pathogens. The binding of Hu-MIF-1 to its cognate receptor
      CD74 was predicted by computer-assisted docking, and it resulted to be very
      similar to the predicted complexes formed by parasite MIFs and human CD74. More
      than 1 plausible conformation of MIFs in the extracellular loops of CD74 may be
      possible as demonstrated by the different predicted conformations of MIF
      orthologs in complex with CD74. Parasite MIFs in complex with CD74 resulted with
      some charged residues oriented to CD74, which was not observed in the Hu-MIF
      1/CD74 complex. Our findings predict the binding mode of Hu-MIF-1 and orthologs
      with CD74, which can assist in the design of novel MIF inhibitors. Whether the
      parasite MIFs function specifically subvert host immune responses to suit the
      parasite is an open question that needs to be further investigated. Future
      research should lead to a better understanding of parasite MIF action in the
      parasite biology.

PMID- 28513080
TI  - Sleep Disorders and RBD: What Would James Parkinson Think?

PMID- 28513079
TI  - REM Sleep Behavior Disorder in Parkinson's Disease and Other Synucleinopathies.
AB  - Rapid eye movement sleep behavior disorder is characterized by dream enactment
      and complex motor behaviors during rapid eye movement sleep and rapid eye
      movement sleep atonia loss (rapid eye movement sleep without atonia) during
      polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or
      symptomatic and in both settings is highly associated with synucleinopathy
      neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies,
      multiple system atrophy, and pure autonomic failure. Rapid eye movement sleep
      behavior disorder frequently manifests years to decades prior to overt motor,
      cognitive, or autonomic impairments as the presenting manifestation of
      synucleinopathy, along with other subtler prodromal "soft" signs of hyposmia,
      constipation, and orthostatic hypotension. Between 35% and 91.9% of patients
      initially diagnosed with idiopathic rapid eye movement sleep behavior disorder at
      a sleep center later develop a defined neurodegenerative disease. Less is known
      about the long-term prognosis of community-dwelling younger patients, especially
      women, and rapid eye movement sleep behavior disorder associated with
      antidepressant medications. Patients with rapid eye movement sleep behavior
      disorder are frequently prone to sleep-related injuries and should be treated to
      prevent injury with either melatonin 3-12 mg or clonazepam 0.5-2.0 mg to limit
      injury potential. Further evidence-based studies about rapid eye movement sleep
      behavior disorder are greatly needed, both to enable accurate prognostic
      prediction of end synucleinopathy phenotypes for individual patients and to
      support the application of symptomatic and neuroprotective therapies. Rapid eye
      movement sleep behavior disorder as a prodromal synucleinopathy represents a
      defined time point at which neuroprotective therapies could potentially be
      applied for the prevention of Parkinson's disease, dementia with Lewy bodies,
      multiple system atrophy, and pure autonomic failure. (c) 2017 International
      Parkinson and Movement Disorder Society.

PMID- 28513081
TI  - Nomenclature of genetic movement disorders: Recommendations of the International
      Parkinson and Movement Disorder Society task force.

PMID- 28513082
TI  - Impact of Osteoarthritis on Difficulty Walking: A Population-Based Study.
AB  - OBJECTIVE: To assess the relationship of hip and knee osteoarthritis (OA) to
      walking difficulty. METHODS: A population cohort ages <=55 years recruited from
      1996 to 1998 (n = 28,451) completed a standardized questionnaire assessing
      demographics, health conditions, joint symptoms, and functional limitations,
      including difficulty walking in the past 3 months. Survey data were linked to
      health administrative databases; self-report and administrative data were used to
      identify health conditions. Hip/knee OA was defined as self-reported swelling,
      pain, or stiffness in a hip or knee lasting >=6 weeks in the past 3 months
      without an inflammatory arthritis diagnosis. Using multivariable logistic
      regression, we examined the determinants of walking difficulty and constructed a
      clinical nomogram. RESULTS: A total of 18,490 cohort participants were eligible
      (mean age 68 years, 60% women), and 25% reported difficulty walking. Difficulty
      walking was significantly and independently associated with older age, female
      sex, body mass index, and several health conditions. Of the conditions examined,
      the likelihood of walking difficulty was greatest with hip and knee OA and
      increased with the number of hip/knee joints affected. The predicted probability
      of difficulty walking for a 60-year-old middle-income, normal-weight woman was 5
      10% with no health conditions, 10-20% with diabetes mellitus and cardiovascular
      (CV) disease, 40% with OA in 2 hips/knees, 60-70% with diabetes mellitus, CV
      disease, and OA in 2 hips/knees, and 80% with diabetes mellitus, CV disease, and
      OA in all hips/knees. CONCLUSION: In a population cohort, symptomatic hip/knee OA
      was the strongest contributor to walking difficulty. Given the importance of
      walking to engagement in physical activity for chronic disease management,
      greater attention to OA is warranted.

PMID- 28513084
TI  - Exploring the role of occupational therapy in caring for cancer survivors in
      Australia: A cross sectional study.
AB  - BACKGROUND/AIM: With increasing rates of cancer survival in Australia, more
      people are living with long-term side effects of cancer and its treatment, and
      cancer survivorship is now considered a distinct phase of cancer care. While
      occupational therapists play an integral role in multidisciplinary care for
      people with chronic conditions, there is little evidence documenting the
      occupational therapy role for people living with chronic cancer-related
      conditions. This study aimed to explore the views of Australian occupational
      therapists about current practice and what constitutes best practice for cancer
      survivors. METHODS: A cross-sectional online survey was developed and distributed
      via emailed invitations to the Occupational Therapy Australia membership to
      collect responses from occupational therapists in a range of locations and
      practice settings around Australia. RESULTS: A total of 204 completed surveys
      were returned (response rate of 4%). More than 70% (n = 143) of respondents
      worked with people with cancer at least sometimes and most worked in acute
      (13.8%, n = 28) or community (11.2%, n = 23) settings. Participants rated
      equipment provision as the most common intervention (94%, n = 192), followed by
      energy conservation (91%, n = 185) and pressure care (78%, n = 160). Lack of
      funding for occupational therapy positions and a lack of recognition of the role
      of occupational therapy by health professionals and consumers were identified as
      key barriers to survivorship care. CONCLUSION: Research is needed to provide
      evidence supporting the role and practice of occupational therapy with cancer
      survivors. Collaborative work with multidisciplinary teams is needed to develop
      long-term routine treatment pathways that include occupational therapy
      interventions.

PMID- 28513083
TI  - Screen-printed ambulatory electrode set enables accurate diagnostics of sleep
      bruxism.
AB  - Currently, definite diagnosis of sleep bruxism requires polysomnography. However,
      it is restrictedly available, and too cumbersome and expensive for the purpose.
      The aim of this study was to introduce an ambulatory electrode set and evaluate
      its feasibility for more cost-effective diagnostics of sleep bruxism. Six self
      assessed bruxers (one male, five females; aged 21-58 years) and six healthy
      controls (four males, two females, aged 21-25 years) underwent a standard
      polysomnographic study and a concurrent study with the ambulatory electrode set.
      Bruxism events, cortical arousals and sleep stages were scored for the two
      montages separately in a random order, and obtained sleep parameters were
      compared. In addition, the significance of video recording and sleep stage
      scoring for the diagnostic accuracy of ambulatory electrode set was determined.
      Ambulatory electrode set yielded similar diagnoses as standard polysomnography in
      all subjects. However, compared with standard polysomnography the median
      (interquartile range) tonic bruxism event index was significantly higher in the
      control group [+0.38 (+0.08 to +0.56) events per hour, P = 0.046], and the phasic
      bruxism event index was significantly lower in the bruxer group [-0.44 (-1.30 to
      +0.07) events per hour, P = 0.046]. Exclusion of video recording and both video
      recording and sleep stage scoring from analysis increased overestimation of the
      tonic bruxism event index in the control group +0.86 (+0.42 to +1.03) and +1.19
      (+0.55 to +1.39) events per hour, P = 0.046 and P = 0.028, respectively],
      resulting in one misdiagnosed control subject. To conclude, ambulatory electrode
      set is a sensitive method for ambulatory diagnostics of sleep bruxism, and video
      recording and sleep stage scoring help reaching the highest specificity of sleep
      bruxism diagnostics.

PMID- 28513085
TI  - Systematic review with meta-analysis: endoscopic dilation is highly effective and
      safe in children and adults with eosinophilic oesophagitis.
AB  - BACKGROUND: Oesophageal dilation is frequently used as an adjunct treatment to
      alleviate symptoms that develop from fibrostenotic remodelling in eosinophilic
      oesophagitis (EoE). Earlier reports described an increased risk of complications
      associated with dilation. AIM: Perform a systematic review and meta-analysis to
      assess the efficacy and safety of endoscopic dilation in children and adults with
      EoE. METHODS: Professional librarians searched MEDLINE, EMBASE, the Cochrane
      library, Scopus, and Web of Science for articles in any language describing
      studies of dilation in EoE through December 2016. Studies were selected and data
      were abstracted independently and in duplicate. Random effects modelling was used
      to generate summary estimates for clinical improvement and complications
      (haemorrhage, perforation, hospitalisation, and death). RESULTS: The search
      resulted in 3495 references, of which 27 studies were included in the final
      analysis. The studies described 845 EoE patients, including 87 paediatric
      patients, who underwent a total of 1820 oesophageal dilations. The median number
      of dilations was 3 (range: 1-35). Clinical improvement occurred in 95% of
      patients (95% CI: 90%-98%, I2 : 10%, 17 studies). Perforation occurred in 0.38%
      (95% CI: 0.18%-0.85%, I2 : 0%, 27 studies), haemorrhage in 0.05% (95% CI: 0%
      0.3%, I2 : 0%, 18 studies), and hospitalisation in 0.67% (95% CI: 0.3%-1.1%, I2 :
      44%, 24 studies). No deaths occurred (95% CI: 0%-0.2% I2 : 0%, 25 studies).
      CONCLUSIONS: Endoscopic dilation is consistently effective in children and adults
      with EoE, resulting in improvement in 95% of patients with very low rates (<1%)
      of major complications.

PMID- 28513086
TI  - Photoluminescent properties of novel design heteroleptic Zn(II) complexes.
AB  - Three novel heteroleptic Zn(II) complexes containing 8-hydroxy quinoline and
      various pyrazolone-based derivatives were synthesized and their structures
      confirmed by 1 H-nuclear magnetic resonance, mass spectrometry, Fourier transform
      infra-red spectroscopy, UV-vis analysis and element analysis. All three complexes
      showed good photoluminescence properties in the solid state and in solution in
      the maximum emission range from 475 to 490 nm with a quantum yield of 0.45 to
      0.51. Absorption spectra revealed that the complexes possessed a maximum
      absorption range of 272-281 nm with a band gap of 2.59-2.68 eV. The highest
      occupied molecular orbital and lowest unoccupied molecular orbital of all the
      complexes were determine by cyclic voltammetry. All complexes displayed high
      thermal stability. These characteristics were assessed to find suitability for an
      alternative cheap light emitter for organic light-emitting diodes.

PMID- 28513087
TI  - Kangaroo mother care to reduce morbidity and mortality in low birth weight
      infants.

PMID- 28513089
TI  - Editorial overview: Celebrating the advances in cell biology from China.

PMID- 28513088
TI  - Psoas muscle area is not representative of total skeletal muscle area in the
      assessment of sarcopenia in ovarian cancer.
AB  - BACKGROUND: Computed tomography measurements of total skeletal muscle area can
      detect changes and predict overall survival (OS) in patients with advanced
      ovarian cancer. This study investigates whether assessment of psoas muscle area
      reflects total muscle area and can be used to assess sarcopenia in ovarian cancer
      patients. METHODS: Ovarian cancer patients (n = 150) treated with induction
      chemotherapy and interval debulking were enrolled retrospectively in this
      longitudinal study. Muscle was measured cross sectionally with computed
      tomography in three ways: (i) software quantification of total skeletal muscle
      area (SMA); (ii) software quantification of psoas muscle area (PA); and (iii)
      manual measurement of length and width of the psoas muscle to derive the psoas
      surface area (PLW). Pearson correlation between the different methods was
      studied. Patients were divided into two groups based on the extent of change in
      muscle area, and agreement was measured with kappa coefficients. Cox-regression
      was used to test predictors for OS. RESULTS: Correlation between SMA and both
      psoas muscle area measurements was poor (r = 0.52 and 0.39 for PA and PLW,
      respectively). After categorizing patients into muscle loss or gain, kappa
      agreement was also poor for all comparisons (all kappa < 0.40). In regression
      analysis, SMA loss was predictive of poor OS (hazard ratio 1.698 (95%CI 1.038
      2.778), P = 0.035). No relationship with OS was seen for PA or PLW loss.
      CONCLUSIONS: Change in psoas muscle area is not representative of total muscle
      area change and should not be used to substitute total skeletal muscle to predict
      survival in patients with ovarian cancer.

PMID- 28513090
TI  - Benchmarking a computational design method for the incorporation of metal ion
      binding sites at symmetric protein interfaces.
AB  - The design of novel metal-ion binding sites along symmetric axes in protein
      oligomers could provide new avenues for metalloenzyme design, construction of
      protein-based nanomaterials and novel ion transport systems. Here, we describe a
      computational design method, symmetric protein recursive ion-cofactor sampling
      (SyPRIS), for locating constellations of backbone positions within oligomeric
      protein structures that are capable of supporting desired symmetrically
      coordinated metal ion(s) chelated by sidechains (chelant model). Using SyPRIS on
      a curated benchmark set of protein structures with symmetric metal binding sites,
      we found high recovery of native metal coordinating rotamers: in 65 of the 67
      (97.0%) cases, native rotamers featured in the best scoring model while in the
      remaining cases native rotamers were found within the top three scoring models.
      In a second test, chelant models were crossmatched against protein structures
      with identical cyclic symmetry. In addition to recovering all native placements,
      10.4% (8939/86013) of the non-native placements, had acceptable geometric
      compatibility scores. Discrimination between native and non-native metal site
      placements was further enhanced upon constrained energy minimization using the
      Rosetta energy function. Upon sequence design of the surrounding first-shell
      residues, we found further stabilization of native placements and a small but
      significant (1.7%) number of non-native placement-based sites with favorable
      Rosetta energies, indicating their designability in existing protein interfaces.
      The generality of the SyPRIS approach allows design of novel symmetric metal
      sites including with non-natural amino acid sidechains, and should enable the
      predictive incorporation of a variety of metal-containing cofactors at symmetric
      protein interfaces.

PMID- 28513091
TI  - Estimation of exposure distribution adjusting for association between exposure
      level and detection limit.
AB  - In environmental exposure studies, it is common to observe a portion of exposure
      measurements to fall below experimentally determined detection limits (DLs). The
      reverse Kaplan-Meier estimator, which mimics the well-known Kaplan-Meier
      estimator for right-censored survival data with the scale reversed, has been
      recommended for estimating the exposure distribution for the data subject to DLs
      because it does not require any distributional assumption. However, the reverse
      Kaplan-Meier estimator requires the independence assumption between the exposure
      level and DL and can lead to biased results when this assumption is violated. We
      propose a kernel-smoothed nonparametric estimator for the exposure distribution
      without imposing any independence assumption between the exposure level and DL.
      We show that the proposed estimator is consistent and asymptotically normal.
      Simulation studies demonstrate that the proposed estimator performs well in
      practical situations. A colon cancer study is provided for illustration.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28513092
TI  - Pharmacokinetics and pharmacodynamics of meldonium in exercised thoroughbred
      horses.
AB  - Although developed as a therapeutic medication, meldonium has found widespread
      use in human sports and was recently added to the World Anti-Doping Agency's list
      of prohibited substances. Its reported abuse potential in human sports has led to
      concern by regulatory authorities about the possible misuse of meldonium in
      equine athletics. The potential abuse in equine athletes along with the limited
      data available regarding the pharmacokinetics and pharmacodynamics of meldonium
      in horses necessitates further study. Eight exercised adult thoroughbred horses
      received a single oral dose of 3.5, 7.1, 14.3 or 21.4 mg/kg of meldonium. Blood
      and urine samples were collected and analyzed using liquid chromatography tandem
      mass spectrometry. Pharmacokinetic parameters were determined using non
      compartmental analysis. Maximum serum concentrations ranged from 440.2 to 1147
      ng/mL and the elimination half-life from 422 to 647.8 h. Serum concentrations
      were below the limit of quantitation by days 4, 7, 12 and 12 for doses of 3.5,
      7.1, 14.3 and 21.4 mg/kg, respectively. Urine concentrations were below the limit
      of detection by day 44 following administration of 3.5 mg/kg and day 51 for all
      other dose groups. No adverse effects were observed following meldonium
      administration. While the group numbers were small, changes in heart rate were
      observed in the 3.5 mg/kg dose group (n = 1). Glucose concentrations changed
      significantly in all dose groups studied (n = 2 per dose group). Similar to that
      reported for humans, the detection time of meldonium in biological samples
      collected from horses is prolonged, which should allow for satisfactory
      regulation in performance horses. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28513093
TI  - Treatment and outcomes of patients presenting to an adult emergency department
      involuntarily with substance misuse.
AB  - Alcohol and other drug (AOD) use is common in our society. The use of these
      substances flow throughout all areas of healthcare, and is especially prevalent
      in patients presenting to the emergency department with signs of mental illness.
      At the extreme end of these presentations patients present involuntarily with
      either police or ambulance officers. The aim of this study was to identify and
      describe the population presenting to the ED involuntarily with and without
      substance misuse as a precipitating factor. Quantitative descriptive analysis was
      used to describe this population between April and June 2015. In patients
      presenting to one large inner city emergency department involuntarily, 30% had
      alcohol or other drug misuse as a precipitating factor. Patients who
      involuntarily presented with alcohol and other misuse stay longer in the
      emergency department then others that do not have alcohol or other drug misuse.
      These patients represent frequently, with over 50% representing at 90 days
      however this was not associated with alcohol or other drug misuse. Almost all
      patients who present involuntarily are discharged home post review by a mental
      health team. Significant improvements in care can be made in this population if
      the opportunistic treatment of both mental illness and AOD misuse is completed in
      the emergency department.

PMID- 28513094
TI  - Chemiluminescence detection of trace iodide with flow injection analysis of KMnO4
      -carbon dots system.
AB  - Ultra-weak chemiluminescence (CL) from the reaction of iodide and KMnO4 was
      strongly enhanced by carbon nanodots (CNDs) in an acidic medium. The CL intensity
      was directly proportional to the concentration of iodide in the solution.
      Therefore, a flow-injection CL system with high sensitivity, selectivity and
      reproducibility is proposed for the determination of iodide. The proposed method
      exhibited advantages over a linear range of 3.0 * 10-6 -1.0 * 10-4  mol/L and had
      a detection limit of 3.5 * 10-7  mol/L. The method was successfully applied to
      the evaluation of iodide in food samples with recoveries of between 96 and 103%.
      The relative standard deviations were 2.1 and 4.1% for intra- and inter-assay
      precision, respectively.

PMID- 28513095
TI  - Research of the master-slave robot surgical system with the function of force
      feedback.
AB  - BACKGROUND: Surgical robots lack force feedback, which may lead to operation
      errors. In order to improve surgical outcomes, this research developed a new
      master-slave surgical robot, which was designed with an integrated force sensor.
      METHODS: The new structure designed for the master-slave robot employs a force
      feedback mechanism. A six-dimensional force sensor was mounted on the tip of the
      slave robot's actuator. Sliding model control was adopted to control the slave
      robot. According to the movement of the master system manipulated by the surgeon,
      the slave's movement and the force feedback function were validated. RESULTS: The
      motion was completed, the standard deviation was calculated, and the force data
      were detected. Hence, force feedback was realized in the experiment. CONCLUSIONS:
      The surgical robot can help surgeons to complete trajectory motions with haptic
      sensation.

PMID- 28513096
TI  - Is the oral fungal pathogen Candida albicans a cariogen?
AB  - Pathobiology of dental caries is complex. Data from recent molecular
      microbiologic studies have further redefined the role of the oral microbiome in
      the etiology of dental caries. This new information challenges the conventional
      view on the hegemony of classic cariogenic prokaryotes such as Streptococcus
      mutans in caries etiology, and raises the intriguing possibility of the
      participation of the eukaryotic oral fungal pathogen Candida in the caries
      process. The virulence attributes of Candida species such as their acidogenicity
      and aciduric nature, the ability to develop profuse biofilms, ferment and
      assimilate dietary sugars, and produce collagenolytic proteinases are all
      indicative of their latent cariogenic potential. Based on the above, oral
      candidal counts have been used by some as a caries risk indicator. On the
      contrary, other studies suggest that Candida is merely a passenger extant in an
      acidic cariogenic milieu, and not a true pathogen. In this review, we critically
      examine the varying roles of Candida, and traditionally accepted cariogens such
      as the mutans group of streptococci in the pathobiology of dental caries. The
      weight of available data tends to imply that Candida may play a pivotal role as a
      secondary agent perpetuating the carious process, especially in dentinal caries.

PMID- 28513098
TI  - Non-alcoholic fatty liver disease and type 2 diabetes: Importance of glycemic
      control.

PMID- 28513097
TI  - Evidence for a peptidoglycan-like structure in Orientia tsutsugamushi.
AB  - Bacterial cell walls are composed of the large cross-linked macromolecule
      peptidoglycan, which maintains cell shape and is responsible for resisting
      osmotic stresses. This is a highly conserved structure and the target of numerous
      antibiotics. Obligate intracellular bacteria are an unusual group of organisms
      that have evolved to replicate exclusively within the cytoplasm or vacuole of a
      eukaryotic cell. They tend to have reduced amounts of peptidoglycan, likely due
      to the fact that their growth and division takes place within an osmotically
      protected environment, and also due to a drive to reduce activation of the host
      immune response. Of the two major groups of obligate intracellular bacteria, the
      cell wall has been much more extensively studied in the Chlamydiales than the
      Rickettsiales. Here, we present the first detailed analysis of the cell envelope
      of an important but neglected member of the Rickettsiales, Orientia
      tsutsugamushi. This bacterium was previously reported to completely lack
      peptidoglycan, but here we present evidence supporting the existence of a
      peptidoglycan-like structure in Orientia, as well as an outer membrane containing
      a network of cross-linked proteins, which together confer cell envelope
      stability. We find striking similarities to the unrelated Chlamydiales,
      suggesting convergent adaptation to an obligate intracellular lifestyle.

PMID- 28513099
TI  - Syntheses, analytical and pharmacological characterizations of the 'legal high' 4
      [1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues.
AB  - New psychoactive substances (NPS) are commonly referred to as 'research
      chemicals', 'designer drugs' or 'legal highs'. One NPS class is represented by
      dissociative anesthetics, which include analogues of the arylcyclohexylamine
      phencyclidine (PCP), ketamine and diphenidine. A recent addition to the NPS
      market was 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo), a morpholine
      analogue of 3-MeO-PCP. Although suspected to have dissociative effects in users,
      information about its pharmacological profile is not available. From clinical and
      forensic perspectives, detailed analytical data are needed for identification,
      especially when facing the presence of positional isomers, as these are
      frequently unavailable commercially. This study presents the analytical and
      pharmacological characterization of 3-MeO-PCMo along with five additional
      analogues, namely the 2- and 4-MeO-PCMo isomers, 3,4-methylenedioxy-PCMo (3,4-MD
      PCMo), 3-Me-PCMo and PCMo. All six arylcyclohexylmorpholines were synthesized and
      characterized using chromatographic, mass spectrometric and spectroscopic
      techniques. The three positional isomers could be differentiated and the identity
      of 3-MeO-PCMo obtained from an internet vendor was verified. All six compounds
      were also evaluated for affinity at 46 central nervous system receptors including
      the N-methyl-d-aspartate receptor (NMDAR), an important target for dissociative
      anesthetics such as PCP and ketamine. In vitro binding studies using (+)-[3-3 H]
      MK-801 in rat forebrain preparations revealed moderate affinity for NMDAR in the
      rank order of 3-Me >3-MeO > PCMo >3,4-MD > 2-MeO > 4-MeO-PCMo. 3-MeO-PCMo was
      found to have moderate affinity for NMDAR comparable to that of ketamine, and had
      an approximate 12-fold lower affinity than PCP. These results support the
      anecdotal reports of dissociative effects from 3-MeO-PCMo in humans.

PMID- 28513100
TI  - Function of bacteriophage G7C esterase tailspike in host cell adsorption.
AB  - Bacteriophages recognize and bind to their hosts with the help of receptor
      binding proteins (RBPs) that emanate from the phage particle in the form of
      fibers or tailspikes. RBPs show a great variability in their shapes, sizes, and
      location on the particle. Some RBPs are known to depolymerize surface
      polysaccharides of the host while others show no enzymatic activity. Here we
      report that both RBPs of podovirus G7C - tailspikes gp63.1 and gp66 - are
      essential for infection of its natural host bacterium E. coli 4s that populates
      the equine intestinal tract. We characterize the structure and function of gp63.1
      and show that unlike any previously described RPB, gp63.1 deacetylates surface
      polysaccharides of E. coli 4s leaving the backbone of the polysaccharide intact.
      We demonstrate that gp63.1 and gp66 form a stable complex, in which the N
      terminal part of gp66 serves as an attachment site for gp63.1 and anchors the
      gp63.1-gp66 complex to the G7C tail. The esterase domain of gp63.1 as well as
      domains mediating the gp63.1-gp66 interaction is widespread among all three
      families of tailed bacteriophages.

PMID- 28513101
TI  - Industrialization of a perfusion bioreactor: Prime example of a non
      straightforward process.
AB  - Bioreactors are essential enabling technologies for the translation of advanced
      therapies medicinal products from the research field towards a successful
      clinical application. In order to speed up the translation and the spread of
      novel tissue engineering products into the clinical routine, tissue engineering
      bioreactors should evolve from laboratory prototypes towards industrialized
      products. In this work, we thus challenged the industrialization process of a
      novel technological platform, based on an established research prototype of
      perfusion bioreactor, following a GMP-driven approach. We describe how the
      combination of scientific background, intellectual property, start-up factory
      environment, wise industrial advice in the biomedical field, design, and
      regulatory consultancy allowed us to turn a previously validated prototype
      technology into an industrial product suitable for serial production with
      improved replicability and user-friendliness. The solutions implemented enhanced
      aesthetics, ergonomics, handling, and safety of the bioreactor, and they allowed
      compliance with the fundamental requirements in terms of traceability,
      reproducibility, efficiency, and safety of the manufacturing process of advanced
      therapies medicinal products. The result is an automated incubator-compatible
      device, housing 12 disposable independent perfusion chambers for seeding and
      culture of any perfusable tissue. We validated the cell seeding process of the
      industrialized bioreactor by means of the Design of Experiment approach, whilst
      the effectiveness of perfusion culture was evaluated in the context of bone
      tissue engineering.

PMID- 28513103
TI  - A systematic review and meta-analysis of interval training versus moderate
      intensity continuous training on body adiposity.
AB  - Interval training (including high-intensity interval training [HIIT] and sprint
      interval training [SIT]) is promoted in both scientific and lay media as being a
      superior and time-efficient method for fat loss compared with traditional
      moderate-intensity continuous training (MICT). We evaluated the efficacy of
      HIIT/SIT when directly compared with MICT for the modulation of body adiposity.
      Databases were searched to 31 August 2016 for studies with exercise training
      interventions with minimum 4-week duration. Meta-analyses were conducted for
      within-group and between-group comparisons for total body fat percentage (%) and
      fat mass (kg). To investigate heterogeneity, we conducted sensitivity and meta
      regression analyses. Of the 6,074 studies netted, 31 were included. Within-group
      analyses demonstrated reductions in total body fat (%) (HIIT/SIT: -1.26 [95% CI: 
      1.80; -0.72] and MICT: -1.48 [95% CI: -1.89; -1.06]) and fat mass (kg) (HIIT/SIT:
      -1.38 [95% CI: -1.99; -0.77] and MICT: -0.91 [95% CI: -1.45; -0.37]). There were
      no differences between HIIT/SIT and MICT for any body fat outcome. Analyses
      comparing MICT with HIIT/SIT protocols of lower time commitment and/or energy
      expenditure tended to favour MICT for total body fat reduction (p = 0.09).
      HIIT/SIT appears to provide similar benefits to MICT for body fat reduction,
      although not necessarily in a more time-efficient manner. However, neither short
      term HIIT/SIT nor MICT produced clinically meaningful reductions in body fat.

PMID- 28513102
TI  - How bilingualism protects the brain from aging: Insights from bimodal bilinguals.
AB  - Bilingual experience can delay cognitive decline during aging. A general
      hypothesis is that the executive control system of bilinguals faces an increased
      load due to controlling two languages, and this increased load results in a more
      "tuned brain" that eventually creates a neural reserve. Here we explored whether
      such a neuroprotective effect is independent of language modality, i.e., not
      limited to bilinguals who speak two languages but also occurs for bilinguals who
      use a spoken and a signed language. We addressed this issue by comparing bimodal
      bilinguals to monolinguals in order to detect age-induced structural brain
      changes and to determine whether we can detect the same beneficial effects on
      brain structure, in terms of preservation of gray matter volume (GMV), for
      bimodal bilinguals as has been reported for unimodal bilinguals. Our GMV analyses
      revealed a significant interaction effect of age * group in the bilateral
      anterior temporal lobes, left hippocampus/amygdala, and left insula where bimodal
      bilinguals showed slight GMV increases while monolinguals showed significant age
      induced GMV decreases. We further found through cortical surface-based
      measurements that this effect was present for surface area and not for cortical
      thickness. Moreover, to further explore the hypothesis that overall bilingualism
      provides neuroprotection, we carried out a direct comparison of GMV, extracted
      from the brain regions reported above, between bimodal bilinguals, unimodal
      bilinguals, and monolinguals. Bilinguals, regardless of language modality,
      exhibited higher GMV compared to monolinguals. This finding highlights the
      general beneficial effects provided by experience handling two language systems,
      whether signed or spoken. Hum Brain Mapp 38:4109-4124, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28513104
TI  - Novelty seeking and reward dependence-related large-scale brain networks
      functional connectivity variation during salience expectancy.
AB  - A salience network (SN) anchored in the anterior insula (AI) and dorsal anterior
      cingulate cortex (dACC) plays a key role in switching between brain networks
      during salience detection and attention regulation. Previous fMRI studies have
      associated expectancy behaviors and SN activation with novelty seeking (NS) and
      reward dependence (RD) personality traits. To address the question of how
      functional connectivity (FC) in the SN is modulated by internal (expectancy
      related) salience assignment and different personality traits, 68 healthy
      participants performed a salience expectancy task using functional magnetic
      resonance imaging, and psychophysiological interaction analysis (PPI) was
      conducted to determine salience-related connectivity changes during these
      anticipation periods. Correlation was then evaluated between PPI and personality
      traits, assessed using the temperament and character inventory of 32 male
      participants. During high salience expectancy, SN-seed regions showed reduced FC
      to visual areas and parts of the default mode network, but increased FC to the
      central executive network. With increasing NS, participants showed significantly
      increasing disconnection between right AI and middle cingulate cortex when
      expecting high-salience pictures as compared to low-salience pictures, while
      increased RD also predicted decreased right dACC and caudate FC for high salience
      expectancy. Our findings suggest a direct link between personality traits and
      internal salience processing mediated by differential network integration of the
      SN. SN activity and coordination may therefore be moderated by novelty seeking
      and reward dependency personality traits, which are associated with risk of
      addiction. Hum Brain Mapp 38:4064-4077, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513106
TI  - Cholecystitis in situs inversus totalis.

PMID- 28513107
TI  - Extramedullary leukaemia presenting as cardiac myeloid sarcoma.

PMID- 28513105
TI  - Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and
      attenuates wound healing.
AB  - The bone morphogenic protein signaling (BMP) is intricately involved in the
      quiescence and regulation of stem cells through activation of BMP receptors. Hair
      follicle stem cells play a critical role in cutaneous homeostasis and
      regeneration. Here, we utilize a novel mouse model with targeted overexpression
      of the BMP receptor ALK2/ACVR1 in hair follicle stem cells, to characterize its
      role in skin development and postnatal wound healing. Initial histologic
      evaluation demonstrated significant dysregulation in hair follicle morphogenesis
      in mutant mice. These demonstrated increased numbers of individual hair follicles
      with altered morphology and localization. Mutant follicles were found to exhibit
      elevated proliferative activity as well as increased prevalence of CD34 and ITGA6
      positive follicle stem cells. Interestingly, constitutive overexpression of ALK2
      resulted in attenuation of cutaneous wound healing. These findings demonstrate
      that hair follicle specific ALK2 is intricately involved in maintenance of the
      stem cell niche and wound healing.

PMID- 28513108
TI  - Dermatofibrosarcoma protuberans of the scalp: therapeutic challenges.

PMID- 28513109
TI  - Separation and identification of mouse brain tissue microproteins using top-down
      method with high resolution nanocapillary liquid chromatography mass
      spectrometry.
AB  - Microproteins and endogenous peptides in the brain contain important substances
      that have critical roles in diverse biological processes, contributing to signal
      transduction and intercellular signaling. However, variability in their physical
      or chemical characteristics, such as molecule size, hydrophobicity, and charge
      states, complicate the simultaneous analysis of these compounds, although this
      would be highly beneficial for the field of neuroscience research. Here, we
      present a top-down analytical method for simultaneous analysis of microproteins
      and endogenous peptides using high-resolution nanocapillary LC-MS/MS. This method
      is detergent-free and digestion-free, which allows for extracting and preserving
      intact microproteins and peptides for direct LC-MS analysis. Both higher energy
      collision dissociation and electron-transfer dissociation fragmentations were
      used in the LC-MS analysis to increase the identification rate, and
      bioinformatics tools ProteinGoggle and PEAKS Studio software were utilized for
      database search. In total, we identified 471 microproteins containing 736
      proteoforms, including brain-derived neurotrophic factor and a number of
      fibroblast growth factors. In addition, we identified 599 peptides containing 151
      known or potential neuropeptides such as somatostatin-28 and neuropeptide Y. Our
      approach bridges the gap for the characterization of brain microproteins and
      peptides, which permits quantification of a diversity of signaling molecules for
      biomarker discovery or therapy diagnosis in the future.

PMID- 28513111
TI  - Type 2 Diabetic Patients Fasting on Ramadan in Israel.
AB  - BACKGROUND: Fasting during Ramadan is not mandatory for diabetic patients, but
      the majority of type 2 diabetic patients insist on fasting despite the potential
      risks. These patients represent a challenge not only for themselves, but also for
      healthcare practitioners during this period. This review provides, for the first
      time, healthcare practitioners in Israel with guidelines and recommendations that
      fit the Muslim population for better management of diabetic patients who fast
      during Ramadan, taking into consideration recently published recommendations and
      therapies available in Israel.

PMID- 28513110
TI  - Separation and purification of two minor typical diarrhetic shellfish poisoning
      toxins from harmful marine microalgae via combined liquid chromatography with
      mass spectrometric detection.
AB  - A novel method was developed for the purification of two typical diarrhetic
      shellfish poisoning toxins from toxin-producing marine microalgae using
      macroporous resin, high-speed countercurrent chromatography-mass spectrometry,
      and semipreparative high-performance liquid chromatography-mass spectrometry.
      Analytical high-performance liquid chromatography-mass spectrometry was used for
      identification and purity analysis of okadaic acid and dinophysistoxin-1 because
      they exhibit no visible or ultraviolet absorption. First, four kinds of
      macroporous resins were investigated, and HP-20 macroporous resin was selected
      for the preenrichment and cleanup of the two target toxins. Second, the resin
      purified sample was further purified using high-speed countercurrent
      chromatography coupled with a mass spectrometer. The purities of the obtained
      okadaic acid and dinophysistoxin-1 were 89.0 and 83.0%, respectively, as
      determined through analytical high-performance liquid chromatography-mass
      spectrometry. Finally, further purification was carried out using semipreparative
      high-performance liquid chromatography with mass spectrometry, and the purities
      of the final okadaic acid and dinophysistoxin-1 products were both over 98.0%
      based on the analytical high-performance liquid chromatography-mass spectrometry
      chromatograms and fraction spectra. This work demonstrates that the proposed
      purification process is a powerful method for the preparation of high-purity
      okadaic acid and dinophysistoxin-1 from toxin-producing marine microalgae.
      Moreover, it is particularly important for the purification and preparation of
      minor toxins that exhibit no visible or ultraviolet absorption from harmful
      marine algae.

PMID- 28513112
TI  - Risk of Overweight in Adolescence among Offspring of Diabetic Mothers.

PMID- 28513113
TI  - Retina and Nerve Fiber Layer Thickness in Eyes with Thyroid-Associated
      Ophthalmopathy.
AB  - BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease
      that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%-5%
      have severe sight-threatening disease due to optic neuropathy Optical coherence
      tomography (OCT), the non-invasive imaging technology that yields high-resolution
      cross-sectional images of the retina, provides qualitative and quantitative data
      on the retina. OBJECTIVES: To apply this technique to quantitatively assess
      retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects
      and in patients with TAO to determine their relationship to the severity of the
      orbital disease. METHODS: All patients in the ophthalmology clinic who were
      diagnosed with TAO and underwent OCT imaging as part of their ocular examination
      comprised the study group, and healthy patients who volunteered to undergo OCT
      examination served as controls. Results of the complete ophthalmologic
      examination and OCT findings were collected from medical files, including the
      thickness of the RNFL and the macula. RESULTS: The study comprised 21 patients
      and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula
      thinning compared to healthy subjects. Mean RNFL thickness was correlated with
      the severity of the orbital disease. CONCLUSIONS: The OCT findings suggest that
      the retina is involved in TAO, probably as early as the subclinical stage. This
      highlights the ability of OCT to identify retinal changes earlier and far more
      accurately than is detected today, enabling earlier diagnosis and more timely
      treatment to prevent severe visual sequelae.

PMID- 28513114
TI  - When Cardioversion May Be Complicated.
AB  - BACKGROUND: In recent years cardioversion of atrial fibrillation has become a
      routine procedure, enabling symptomatic functional improvement in most cases.
      However, some patients develop complications after cardioversion. Identifying
      these individuals is an important step toward improving patient outcome.
      OBJECTIVES: To characterize those patients who may not benefit from cardioversion
      or who may develop complications following cardioversion. METHODS: We
      retrospectively analyzed 186 episodes of cardioversion in 163 patients with
      atrial fibrillation who were admitted to our cardiology department between 2008
      and 2013 based on their clinical and echocardiographic data. Patients were
      divided into two groups: those with uncomplicated cardioversion, and those who
      developed complications after cardioversion. RESULTS: Of the 186 episodes,
      cardioversion was done in 112 men (60%) and 74 women (40%), P < 0.00001.
      Complications after cardioversion occurred in 25 patients (13%). These patients
      were generally older (72 vs. 65 years, P < 0.01), were more often diabetic (52%
      vs. 27%, P = 0.005), had undergone emergency cardioversion (64% vs. 40%, P =
      0.01), had left ventricular hypertrophy (left ventricular mass 260 vs. 218 g, P =
      0.01), had larger left atrium (left atrial volume 128 vs. 102 ml, P < 0.009), and
      more often died from complications of cardioversion (48% vs. 16%). They had
      significant mitral regurgitation (20% vs. 4%, P = 0.03) and higher pulmonary
      artery pressure (50 vs. 42 mm Hg, P < 0.02). CONCLUSIONS: People with
      complications after cardioversion tend to be older, are more often diabetic and
      more often have severe mitral regurgitation. In these patients, the decision to
      perform cardioversion should consider the possibility of complications.

PMID- 28513115
TI  - Endarterectomy or Stenting in Severe Asymptomatic Carotid Stenosis.
AB  - BACKGROUND: Stroke is a major cause of death in the western world, and carotid
      endarterectomy has been shown to be effective in treating both symptomatic and
      asymptomatic carotid stenosis. Carotid stenting is a relatively new form of
      treatment for carotid stenosis and few studies have looked specifically at
      asymptomatic patients. OBJECTIVES: To retrospectively examine short- and long
      term results in the treatment of asymptomatic carotid artery stenosis with
      surgery or stenting. METHODS: We retrospectively collected data of all patients
      with asymptomatic carotid stenosis treated by carotid artery stenting or carotid
      endarterectomy in our department from 2006-2007. The primary endpoints were
      stroke, myocardial infarction, or death during the periprocedural period; or any
      ipsilateral stroke, restenosis, or death within 4 years after the procedure.
      RESULTS: The study comprised 409 patients who were treated by either stenting or
      surgery. There was a low morbidity rate in both treatment groups with no
      significant difference in morbidity or mortality between the treatment groups in
      both in the short-term as well as long-term. CONCLUSIONS: Both treatment methods
      have a low morbidity and mortality rate and should be considered for patients
      with few risk factors and a long life expectancy. Treatment method should be
      selected according to the patient's individual risk factors and imaging data.

PMID- 28513116
TI  - Worse Outcome in Patients with Acute Stroke and Atrial Fibrillation Following
      Thrombolysis.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and a common
      cause of ischemic stroke. Stroke patients with AF have been shown to have a
      poorer neurological outcome than stroke patients without AF. OBJECTIVES: To
      determine the impact of pre-existing AF on residual degree of disability in
      patients treated with IV thrombolysis. METHODS: In this case-control study, data
      of 214 stroke patients (63 with AF and 151 without AF) were collected from the
      National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database.
      Stroke severity and outcome were compared using the National Institute of Health
      Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on
      admission and discharge. Demographics and stroke characteristics were also
      compared between the groups. RESULTS: Stroke severity, as determined by NIHSS at
      admission, was higher in the AF group than the non-AF. In the group of patients
      who were treated with intravenous tissue plasminogen activator (tPA), more
      patients had favorable outcomes (mRS = 0-1 on discharge) in the non-AF group than
      in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to
      5.05). CONCLUSIONS: Our study suggests worse outcome in thrombolized patients
      with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor
      prognostic factor for tPA sensitivity regarding the chance of revascularization
      and recovery after intravenous tPA.

PMID- 28513117
TI  - Routine Laboratory Indices as Predictor of Neurological Recovery in Post
      Resuscitation Syndrome Patients Treated with Therapeutic Hypothermia.
AB  - BACKGROUND: Hypothermia is associated with improved outcome in selected survivors
      of cardiac arrest but no single metric enables proper prediction of neurological
      outcome. OBJECTIVES: To explored the association between routine laboratory
      indices of patients treated by hypothermia for cardiac arrest and their
      neurological outcome. METHODS: We retrospectively collected data from survivors
      of cardiac arrest treated with hypothermia for 24 hours and grouped them
      according to their neurological outcome to either "poor" or "favorable". Routine
      laboratory indices were collected at constant time intervals up to one week of
      admission. A comparison between the laboratory values in both groups was
      performed. RESULTS: Between May 2008 to November 2011, 41 consecutive patients
      with a mean age of 54.3 +/- 16.7 years were included in this study. No
      significant correlation was found between routine laboratory indices and the
      neurological outcome. The temporal trend of decay in the serum glucose values and
      the ratio of polymorphonuclears to white blood cells during the first 72 hours
      after admission was steeper in the favorable outcome group (P for trend < 0.05).
      CONCLUSIONS: No single routine laboratory index was associated with neurological
      outcome of survivors of cardiac arrest treated with hypothermia. The temporal
      trends in both serum glucose and polymorphonuclear ratio signal a more intense
      inflammatory response associated with poor outcome.

PMID- 28513118
TI  - Metformin Does Not Induce Hyperlactatemia in Patients Admitted to Internal
      Medicine Ward.
AB  - BACKGROUND: Concerns about metformin-associated lactic acidosis (MALA) prohibit
      the use of metformin in a large subset of diabetic patients, mostly in patients
      with chronic kidney disease. Increasing evidence suggests that the current safety
      regulations may be overly restrictive. OBJECTIVES: To examine the association
      between chronic metformin treatment and lactate level in acute illness on the
      first day of admission to an internal medicine ward. METHODS: We compared
      diabetic and non-diabetic hospitalized patients treated or not treated with
      metformin in different sets of kidney function. RESULTS: A total of 140 patients
      participated in the study, 54 diabetic patients on chronic metformin treatment,
      33 diabetic patients without metformin and 53 patients with no diabetes. Most
      participants were admitted for conditions that prohibit metformin use, such as
      heart failure, hypoxia and sepsis. Average lactate level was significantly higher
      in the diabetes + metformin group compared to the diabetes non-metformin group.
      Metformin treatment was not associated with higher than normal lactate level
      (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as
      the main diagnosis. CONCLUSIONS: Chronic metformin treatment mildly increases
      lactate level, but does not induce hyperlactatemia or lactic acidosis in acute
      illness on the first day of admission to an internal medicine ward. These data
      support the expansion of metformin use.

PMID- 28513119
TI  - Low Borderline Levels of Serum Vitamin B12 May Predict Cognitive Decline in
      Elderly Hip Fracture Patients.
AB  - BACKGROUND: The progression from cognitive impairment to dementia is a
      multifactorial process that involves genetic and environmental factors. Vitamin
      B12 deficiency can be an important factor in the progress from cognitive decline
      to dementia. OBJECTIVES: To examine the relationship between borderline low level
      of vitamin B12 (<= 350 pg/ml) and cognitive decline among a group of elderly hip
      fracture patients. METHODS: This retrospective chart review study was conducted
      in a geriatric rehabilitation ward of a university-affiliated referral hospital.
      It comprised 91 elderly hip fracture patients. Cognition was assessed by the Mini
      Mental State Examination (MMSE) tool. Fasting serum vitamin B12 levels were
      measured within 24 hours after admission to the rehabilitation ward. RESULTS:
      Twenty-two of the patients had vitamin B12 levels <= 350 pg/ml. In a multiple
      linear regression analysis, after adjusting for confounding variables, serum
      vitamin B12 levels <= 350 pg/ml were linked to a higher risk of developing
      cognitive decline (beta coefficient = -0.28, P = 0.008). CONCLUSIONS: In our
      study, serum vitamin B12 levels <= 350 pg/ml, were independently associated with
      lower MMSE scores in elderly hip fracture patients. Serum vitamin B12 may assist
      in identifying patients in the early stages of cognitive decline. This study
      joins others that have reported on the association of low normal range vitamin
      B12 blood levels and conditions like dementia, falls, fractures and frailty. We
      suggest a reexamination of what is currently considered as the normal range of
      vitamin B12 in the elderly.

PMID- 28513120
TI  - Gestational Weight Gain and Its Relationship with Maternal Characteristics.
AB  - BACKGROUND: Both high and insufficient weight gain during pregnancy have been
      associated with adverse outcomes for mothers and their offspring. OBJECTIVES: To
      describe self-reported weight gain during pregnancy, assess the concurrence of
      this weight gain with issued recommendations, and investigate associations
      between lifestyle factors and weight gain. METHODS: In this cross-sectional
      study, 109 pregnant women hospitalized in one gynecological and obstetrics
      department completed questionnaires related to weight gain and lifestyle factors
      such as smoking, diet and exercise. Recommended weight gain was defined by the
      American Congress of Obstetricians and Gynecologists and was compatible with the
      Ministry of Health guidelines in Israel. RESULTS: Fifty-three (49%) participants
      reported weight gain above the recommendation, 31 (28%) met the recommendations
      and 25 (23%) reported weight gain below the recommendations. Characteristics
      associated with high weight gain included past smoking and/or age above 36 years
      and/or body mass index (BMI) above 25 kg/m2. Only 34 women (31%) reported seeking
      professional nutritional counseling during pregnancy. An increased tendency to
      consult a nutritionist was reported among diabetic women. CONCLUSIONS: Only a
      minority of women gained the recommended weight during pregnancy. High BMI and/or
      a history of smoking and/or older age were associated with weight gain above
      recommendations. Particular effort should be directed toward counseling women at
      high risk of weight gain during pregnancy.

PMID- 28513121
TI  - Can Procalcitonin Contribute to the Diagnosis of Clostridium difficile Colitis?
AB  - BACKGROUND: It is a challenge to diagnosis Clostridium difficile colitis.
      OBJECTIVES: To determine, among patients who developed nosocomial diarrhea,
      whether serum procalcitonin (PCT) can distinguish between C. difficile toxin
      (CDT)-positive and CDT-negative patients. METHODS: This prospective study
      included 50 adults (>18 years) who developed diarrhea during hospitalization, 25
      with a positive fecal test for CDT (study group) and 25 CDT negative (control
      group). RESULTS: Baseline demographic and underlying illnesses were similar in
      both groups. Duration of diarrhea was 6 +/- 4 days and 3 +/- 1 in the study and
      control groups, respectively (P = 0.001). Mean blood count was 20 +/- 15 and 9.9
      +/- 4, respectively (P = 0.04). CRP level was higher in the study than in the
      control group (10.9 +/- 7.4 and 6.6 +/- 4.8, P = 0.028). PCT level was higher in
      the study group (4.4 +/- 4.9) than the control group (0.3 +/- 0.5, P = 0.102). A
      PCT level > 2 ng/ml was found in 7/25 patients (28%) and 1/25 (4%), respectively
      [odds ratio 9.33, 95% confidence interval (0.98 to 220), P = 0.049]. Multivariate
      analysis showed that only duration of diarrhea and left shift of peripheral
      leucocytes were significant indicators of CDT (P = 0.014 and P = 0.019,
      respectively). The mortality rate was 12/25 (48%) vs. 5/25 (20%), respectively (P
      = 0.04). CONCLUSIONS: We found a non-significant tendency to higher PCT levels in
      patients with CDT-positive vs. CDT-negative nosocomial diarrhea. However, a PCT
      level > 2 ng/ml may help distinguish between these patients.

PMID- 28513122
TI  - The Many Faces of Non-Classic Congenital Adrenal Hyperplasia.

PMID- 28513123
TI  - Urgent Endoscopic Stapler Zenker's Diverticulotomy in Acute Aphagia.

PMID- 28513124
TI  - Definitive Endovascular Repair of a Brucellar Descending Thoracic Aortic
      Aneurysm.

PMID- 28513125
TI  - Pseudocirrhosis in Metastatic Breast Cancer.

PMID- 28513126
TI  - Type 1 Gaucher disease with fatal outcome in a 17-year-old girl from Kazakhstan.

PMID- 28513129
TI  - Electrodeposited Nickel-Cobalt-Sulfide Catalyst for the Hydrogen Evolution
      Reaction.
AB  - A novel Ni-Co-S-based material prepared by the potentiodynamic deposition from an
      aqueous solution containing Ni2+, Co2+, and thiourea is studied as an
      electrocatalyst for the hydrogen evolution reaction (HER) in a neutral phosphate
      solution. The composition of the catalyst and the HER activity are tuned by
      varying the ratio of the concentrations of Ni2+ and Co2+ ions in the
      electrolytes. Under optimized deposition conditions, the bimetallic Ni-Co-S
      exhibits higher electrocatalytic activity than its monometallic counterparts. The
      Ni-Co-S catalyst requires an overpotential of 150 mV for the HER onset, and 10 mA
      cm-2 current density is obtained at 280 mV overpotential. The catalyst exhibits
      two different Tafel slopes (93 and 70 mV dec-1) indicating two dissimilar
      mechanisms. It is proposed that the catalyst comprises two types of catalytic
      active sites, and they contribute selectively toward HER in different potential
      regions.

PMID- 28513127
TI  - Shear-wave elastography in breast ultrasonography: the state of the art.
AB  - Shear-wave elastography (SWE) is a recently developed ultrasound technique that
      can visualize and measure tissue elasticity. In breast ultrasonography, SWE has
      been shown to be useful for differentiating benign breast lesions from malignant
      breast lesions, and it has been suggested that SWE enhances the diagnostic
      performance of ultrasonography, potentially improving the specificity of
      conventional ultrasonography using the Breast Imaging Reporting and Data System
      criteria. More recently, not only has SWE been proven useful for the diagnosis of
      breast cancer, but has also been shown to provide valuable information that can
      be used as a preoperative predictor of the prognosis or response to chemotherapy.

PMID- 28513130
TI  - Anisotropic Friction of Wrinkled Graphene Grown by Chemical Vapor Deposition.
AB  - Wrinkle structures are commonly seen on graphene grown by the chemical vapor
      deposition (CVD) method due to the different thermal expansion coefficient
      between graphene and its substrate. Despite the intensive investigations focusing
      on the electrical properties, the nanotribological properties of wrinkles and the
      influence of wrinkle structures on the wrinkle-free graphene remain less
      understood. Here, we report the observation of anisotropic nanoscale frictional
      characteristics depending on the orientation of wrinkles in CVD-grown graphene.
      Using friction force microscopy, we found that the coefficient of friction
      perpendicular to the wrinkle direction was ~194% compare to that of the parallel
      direction. Our systematic investigation shows that the ripples and "puckering"
      mechanism, which dominates the friction of exfoliated graphene, plays even a more
      significant role in the friction of wrinkled graphene grown by CVD. The
      anisotropic friction of wrinkled graphene suggests a new way to tune the graphene
      friction property by nano/microstructure engineering such as introducing
      wrinkles.

PMID- 28513128
TI  - Clinical features of recently diagnosed papillary thyroid carcinoma in elderly
      patients aged 65 and older based on 10 years of sonographic experience at a
      single institution in Korea.
AB  - PURPOSE: The aim of this study was to assess the characteristics of papillary
      thyroid carcinoma (PTC) in patients aged 65 and older in order to predict
      postoperative recurrence based on the results of ultrasonographic surveillance.
      METHODS: Among 1,494 patients (200 male and 1,294 female; mean age, 46.6+/-11.3
      years) who underwent surgery for thyroid cancer at our institution between 2006
      and 2015, we retrospectively enrolled 150 PTC patients (29 male and 121 female;
      mean age, 69.4+/-4.2 years). To identify the risk factors for recurrence, we
      analyzed age, gender, multiplicity, size, number, extrathyroidal extension (ETE)
      of the tumor, lymph node metastasis (LNM), type of surgery, and the dose of
      radioactive ablation using a Cox regression model to identify hazard ratios
      (HRs). RESULTS: Among the 115 asymptomatic patients with PTCs detected by
      screening ultrasonography (n=86), other cross-sectional imaging modalities
      (computed tomography or positron emission tomography-computed tomography, n=13),
      or incidentally through a surgical specimen (n=16), 78 patients were confirmed to
      have papillary thyroid microcarcinomas (PTMCs). The other 35 patients presented
      with palpable neck masses (n=25), vocal cord palsy (n=9) or blood-tinged sputum
      (n=1). During the follow-up period (mean, 43.6 months), 17 patients (12.5%)
      experienced recurrence in the neck. None of the patients died due to PTC-related
      recurrence or distant metastasis during the follow-up period. Cox regression
      analysis demonstrated that tumor size (HR, 2.12; P<0.001) and LNM (central LNM:
      HR, 9.08; P=0.004; lateral LNM: HR, 14.71; P=0.002; both central and lateral LNM:
      HR, 58.41; P<0.001) significantly increased the recurrence rate. ETE, LNM, and
      recurrence were significantly less frequent in PTMCs than in non-PTMC (all
      P<0.001). CONCLUSION: PTCs of small size and absent LNM showed significantly
      better prognoses in patients 65 years and older.

PMID- 28513131
TI  - Improved Oxidase Mimetic Activity by Praseodymium Incorporation into Ceria
      Nanocubes.
AB  - Ceria nanocubes (NC) modified with increasing concentrations of praseodymium (5,
      10, 15, and 20 mol %) have been successfully synthesized by a hydrothermal
      method. The as-synthesized Pr-modified ceria nanocubes exhibit an enhanced
      oxidase-like activity on the organic dye TMB within a wide range of
      concentrations and durations. The oxidase activity increases with increasing Pr
      amounts in Pr-modified ceria nanocubes within the investigated concentration
      range. Meanwhile, these Pr-modified ceria nanocubes also show higher reducibility
      than pure ceria nanocubes. The kinetics of their oxidase mimetic activity is
      fitted with the Michaelis-Menten equation. A mechanism has been proposed on how
      the Pr incorporation could affect the energy level of the bands in ceria and
      hence facilitate the TMB oxidation reaction. The presence of Pr3+ species on the
      surface also contributes to the increasing activity of the Pr-modified ceria
      nanocubes present higher oxidase activity than pure ceria nanocubes.

PMID- 28513132
TI  - alpha-Amylase- and Redox-Responsive Nanoparticles for Tumor-Targeted Drug
      Delivery.
AB  - Paclitaxel (PTX) is an effective antineoplastic agent and shows potent antitumor
      activity against a wide spectrum of cancers. Yet, the wide clinical use of PTX is
      limited by its poor aqueous solubility and the side effects associated with its
      current therapeutic formulation. To tackle these obstacles, we report, for the
      first time, alpha-amylase- and redox-responsive nanoparticles based on
      hydroxyethyl starch (HES) for the tumor-targeted delivery of PTX. PTX is
      conjugated onto HES by a redox-sensitive disulfide bond to form HES-SS-PTX, which
      was confirmed by results from NMR, high-performance liquid chromatography-mass
      spectrometry, and Fourier transform infrared spectrometry. The HES-SS-PTX
      conjugates assemble into stable and monodispersed nanoparticles (NPs), as
      characterized with Dynamic light scattering, transmission electron microscopy,
      and atomic force microscopy. In blood, alpha-amylase will degrade the HES shell
      and thus decrease the size of the HES-SS-PTX NPs, facilitating NP extravasation
      and penetration into the tumor. A pharmacokinetic study demonstrated that the HES
      SS-PTX NPs have a longer half-life than that of the commercial PTX formulation
      (Taxol). As a consequence, HES-SS-PTX NPs accumulate more in the tumor compared
      with the extent of Taxol, as shown in an in vivo imaging study. Under reductive
      conditions, the HES-SS-PTX NPs could disassemble quickly as evidenced by their
      triggered collapse, burst drug release, and enhanced cytotoxicity against 4T1
      tumor cells in the presence of a reducing agent. Collectively, the HES-SS-PTX NPs
      show improved in vivo antitumor efficacy (63.6 vs 52.4%) and reduced toxicity in
      4T1 tumor-bearing mice compared with those of Taxol. These results highlight the
      advantages of HES-based alpha-amylase- and redox-responsive NPs, showing their
      great clinical translation potential for cancer chemotherapy.

PMID- 28513133
TI  - Antibacterial Property of a Polyethylene Glycol-Grafted Dental Material.
AB  - Dental materials often cause bacterial adhesion and promote bacterial biofilm
      formation, which brings a series of long-standing and significant problems in
      oral health. However, the current development of antibacterial research in dental
      devices is limited by the lack of materials endowed with good antibacterial
      properties against oral bacteria. Here, we present a new strategy for reducing
      the initial adhesion of bacterial on dental biomaterials by chemically bonding
      long-chain polyethylene glycol. Our work represents an important step toward
      solving the problem of bacterial accumulation on dental devices.

PMID- 28513134
TI  - Silicon Quantum Dots in Dielectric Scattering Media: Broadband Enhancement of
      Effective Absorption Cross Section by Light Trapping.
AB  - We report strong enhancements of the effective absorption cross section and
      photoluminescence (PL) intensity of silicon quantum dots (Si QDs) with 2.8-6.8 nm
      in diameter in a highly scattering dielectric medium. The scattering medium is a
      polymer thin film with submicrometer size pores inside, supporting the resonant
      cavity modes in the visible range. By the scattering associated with the cavity
      modes, efficient light trapping into a polymer film with ~1 MUm in thickness is
      achieved, which leads to 30-40 times enhancement of the effective absorption
      cross section of embedded Si QDs in a green-red wavelength range. The scattering
      medium can also enhance up to 40 times the PL of QDs. Detailed analysis reveals
      that the enhancements of the extraction efficiency as well as the excitation
      efficiency contribute to the PL enhancement.

PMID- 28513135
TI  - Porous MOF with Highly Efficient Selectivity and Chemical Conversion for CO2.
AB  - A new Co(II)-based MOF, {[Co2(tzpa)(OH)(H2O)2].DMF}n (1) (H3tzpa = 5-(4-(tetrazol
      5-yl)phenyl)isophthalic acid), was constructed by employing a tetrazolyl-carboxyl
      ligand H3tzpa. 1 possesses 1D tubular channels that are decorated by MU3-OH
      groups, uncoordinated carboxylate O atoms, and open metal centers generated by
      the removal of coordinated water molecules, leading to high CO2 adsorption
      capacity and significantly selective capture for CO2 over CH4 and CO in the
      temperature range of 298-333 K. Moreover, 1 shows the chemical stability in
      acidic and basic aqueous solutions. Grand canonical Monte Carlo simulations
      identified multiple CO2-philic sites in 1. In addition, the activated 1 as the
      heterogeneous Lewis and Bronsted acid bifunctional catalyst facilitates the
      chemical fixation of CO2 coupling with epoxides into cyclic carbonates under
      ambient conditions.

PMID- 28513137
TI  - Hierarchical Porous Carbon Doped with Iron/Nitrogen/Sulfur for Efficient Oxygen
      Reduction Reaction.
AB  - Hierarchical porous Fe/N/S-doped carbon with a high content of graphitic nitrogen
      (FeNS/HPC) has been successfully synthesized by a facile dual-template method.
      FeNS/HPC shows not only macropores resulting from the dissolution of the SiO2
      template, but abundant mesopores were also obtained after removing the in situ
      generated Fe2O3 nanoparticles on the ultrathin (~4 nm) carbon shell of the
      macropores. Moreover, micropores are produced during the thermal pyrolysis of the
      carbon precursors. With respect to the electrochemical performance in the oxygen
      reduction reaction (ORR), FeNS/HPC not only exceeds other prepared porous carbon
      materials completely but also shows higher onset potential (0.97 vs 0.93 V), half
      wave potentials (0.87 vs 0.83 V), and diffusion current density (5.5 vs 5.3 mA cm
      2) than those of Pt/C. Furthermore, FeNS/HPC also exhibits outstanding stability
      and methanol tolerance, making it a competent candidate for ORR. The following
      aspects contribute to its excellent ORR performance. (1) High content of
      graphitic N (5.1%) and codoping of pyridinic N species, thiophene-S, FeNx, and
      graphitic carbon-encapsulated iron nanoparticles, providing highly active sites.
      (2) The hierarchical porous mesh structure with micro-, meso-, and macroporosity,
      accelerating the mass transfer and facilitating full utilization of the active
      sites. (3) The high specific surface area (1148 m2 g-1) of the graphitic carbon
      shell, assuring a large interface and rapid electron conduction for ORR.

PMID- 28513136
TI  - Cold Chain-Free Storable Hydrogel for Infant-Friendly Oral Delivery of
      Amoxicillin for the Treatment of Pneumococcal Pneumonia.
AB  - Pneumonia is the major cause of death in children under five, particularly in
      developing countries. Antibiotics such as amoxicillin greatly help in mitigating
      this problem. However, there is a lack of an infant/toddler-friendly formulation
      for countries with limited clean water orr electricity. Here, we report the
      development of a shear-thinning hydrogel system for the oral delivery of
      amoxicillin to infant/toddler patients, without the need of clean water and
      refrigeration. The hydrogel formulation consists of metolose (hydroxypropyl
      methylcellulose) and amoxicillin. It preserves the structural integrity of
      antibiotics and their antibacterial activity over 12 weeks at room temperature.
      Pharmacokinetic profiling of mice reveals that the hydrogel formulation increases
      the bioavailability of drugs by ~18% compared to that with aqueous amoxicillin
      formulation. More importantly, oral gavage of this formulation in a mouse model
      of secondary pneumococcal pneumonia significantly ameliorates inflammatory
      infiltration and tissue damage in lungs, with a 10-fold reduction in bacterial
      counts compared to those in untreated ones. Given the remarkable antibacterial
      efficacy as well as the use of FDA-regulated ingredients (metolose and
      amoxicillin), the hydrogel formulation holds great promise for rapid clinical
      translation.

PMID- 28513138
TI  - In Situ Growth of Mesoporous Silica with Drugs on Titanium Surface and Its
      Biomedical Applications.
AB  - Mesoporous silica has been developed for the modification of titanium surfaces
      that are used as implant materials. Yet, the traditional modification methods
      failed to effectively construct mesoporous silica on the titanium surface evenly
      and firmly, in which the interaction between mesoporous silica and titanium was
      mainly physical. Here, in situ growth of mesoporous silica on a titanium surface
      was performed using a simple evaporation-induced self-assembly strategy.
      Meantime, in situ introduction of drugs (heparin and vancomycin) to mesoporous
      silica was also adopted to improve the drug-loading amount. Both the above
      mentioned processes were completed at the same time. Transmission electron
      microscopy, N2 adsorption-desorption isotherms, Fourier transform infrared
      spectroscopy, scanning electron microscopy, and water contact angle measurements
      were used to characterize the structure of the mesoporous silica film. Results
      indicated that the mesoporous silica film that in situ grew on the titanium
      surface was smooth, thin, transparent, and stable. Cytotoxicity, proliferation
      performance of osteoblast cells, and in vitro and in vivo studies of the
      antibacterial activity of the coating were tested. This is the first study to
      modify the titanium surface by the in situ growth of a mesoporous silica coating
      with two kinds of drugs. The stability of the mesoporous silica coating can be
      attributed to the chemical bonding between dopamine and silicon hydroxyl of the
      mesoporous silica coating, and the smooth surface of mesoporous silica is a
      result of the method of in situ growth. The large amount of drug-loading also
      could be ascribed to the in situ introduction of drugs during the synthetic
      process. The strategy proposed in this work will bring more possibilities for the
      preparation of advanced functional materials based on the combination of
      mesoporous structure and metallic materials.

PMID- 28513140
TI  - Hybrid Prodrug Nanoparticles with Tumor Penetration and Programmed Drug
      Activation for Enhanced Chemoresistant Cancer Therapy.
AB  - Despite nanomedicine having shown great potential for reversing cancer cell
      resistance, the suboptimal transport across multiple biological obstacles
      seriously impedes its reaching targets at an efficacious level, which remains a
      challenging hurdle for clinical success in resistant cancer therapy. Here, a
      lipid-based hybrid nanoparticle was designed to efficiently deliver the
      therapeutics to resistant cells and treat resistant cancer in vivo. The hybrid
      nanoparticles (D-NPs/tetrandrine (TET)) are composed of a pH-responsive prodrug
      1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-doxorubicin (DOX), an
      efflux inhibitor TET, and a surfactant DSPE-[methoxy (poly(ethylene glycol))
      2000] (DSPE-mPEG2000), which hierarchically combatted the sequential
      physiological and pathological barriers of drug resistance and exhibited
      prolonged blood circulation, high tumor accumulation, and deep tumor parenchyma
      penetration. In the meantime, the programmed stepwise activation of encapsulated
      TET and DOX suppressed the function of resistance-related P-glycoprotein in a
      timely manner and facilitated the DOX sustained accommodation in tumor cells.
      Through systematic studies, the results show that such a nanosystem dramatically
      enhances drug potency and significantly overcomes the DOX resistance of breast
      cancer with negligible systemic toxicities. These findings provide new strategies
      to systemically combat chemoresistant cancers.

PMID- 28513139
TI  - One-Step Facile Synthesis of Highly Magnetic and Surface Functionalized Iron
      Oxide Nanorods for Biomarker-Targeted Applications.
AB  - We report a one-step method for facile and sustainable synthesis of magnetic iron
      oxide nanorods (or IONRs) with mean lengths ranging from 25 to 50 nm and mean
      diameters ranging from 5 to 8 nm. The prepared IONRs are highly stable in aqueous
      media and can be surface functionalized for biomarker-targeted applications. This
      synthetic strategy involves the reaction of iron(III) acetylacetonate with
      polyethyleneimine in the presence of oleylamine and phenyl ether, followed by
      thermal decomposition. Importantly, the length and diameter as well as the aspect
      ratio of the prepared IONRs can be controlled by modulating the reaction
      parameters. We show that the resultant IONRs exhibit stronger magnetic properties
      compared to those of the widely used spherical iron oxide nanoparticles (IONPs)
      at the same iron content. The increased magnetic properties are dependent on the
      aspect ratio, with the magnetic saturation gradually increasing from 10 to 75 emu
      g-1 when increasing length of the IONRs, 5 nm in diameter, from 25 to 50 nm. The
      magnetic resonance imaging (MRI) contrast-enhancing effect, as measured in terms
      of the transverse relaxivity, r2, increased from 670.6 to 905.5 mM-1 s-1, when
      increasing the length from 25 to 50 nm. When applied to the immunomagnetic cell
      separation of the transferrin receptor (TfR)-overexpressed medulloblastoma cells
      using transferrin (Tf) as the targeting ligand, Tf-conjugated IONRs can capture
      92 +/- 3% of the targeted cells under a given condition (2.0 * 104 cells/mL, 0.2
      mg Fe/mL concentration of magnetic materials, and 2.5 min of incubation time)
      compared to only 37 +/- 2% when using the spherical IONPs, and 14 +/- 2% when
      using commercially available magnetic beads, significantly improving the
      efficiency of separating the targeted cells.

PMID- 28513141
TI  - Application of Cu3InSnSe5 Heteronanostructures as Counter Electrodes for Dye
      Sensitized Solar Cells.
AB  - In this research, we reported the synthesis of quaternary Cu3InSnSe5
      nanoparticles with uniform size distribution and morphology for the first time
      through delicate controls over the chemical reaction kinetics. On the basis of
      the preparation strategy of Cu3InSnSe5 nanoparticles, Pt-Cu3InSnSe5 and Au
      Cu3InSnSe5 heteronanostructures were designed and yielded using a simple and
      efficient seed growth method. These two heteronanostructures remained
      monodispersed without presence of any Cu3InSnSe5 nanocrystal impurities. To
      explore their application potentials for dye-sensitized solar cells, counter
      electrodes consisting of individual Cu3InSnSe5, Pt-Cu3InSnSe5, or Au-Cu3InSnSe5
      constituents were fabricated. Current density-voltage (J-V) characteristics
      evaluation reveals that Cu3InSnSe5 nanoparticles, Pt-Cu3InSnSe5 and Au-Cu3InSnSe5
      heterostructured nanoparticles display a comparative power conversion efficiency
      (PCE) of 5.8%, 7.6%, and 6.5% to that of a Pt-based counter electrode (7.9%),
      respectively. As such, we believe that the reported preparation strategy could
      provide new insights to the design and manufacture of counter electrode materials
      with controlled structure, morphology, and optimized power conversion efficiency
      for dye-sensitized solar cells.

PMID- 28513142
TI  - 12,13-Aziridinyl Epothilones. Stereoselective Synthesis of Trisubstituted
      Olefinic Bonds from Methyl Ketones and Heteroaromatic Phosphonates and Design,
      Synthesis, and Biological Evaluation of Potent Antitumor Agents.
AB  - The synthesis and biological evaluation of a series of 12,13-aziridinyl
      epothilone B analogues is described. These compounds were accessed by a
      practical, general process that involved a 12,13-olefinic methyl ketone as a
      starting material obtained by ozonolytic cleavage of epothilone B followed by
      tungsten-induced deoxygenation of the epoxide moiety. The attachment of the
      aziridine structural motif was achieved by application of the Ess-Kurti-Falck
      aziridination, while the heterocyclic side chains were introduced via
      stereoselective phosphonate-based olefinations. In order to ensure high (E)
      selectivities for the latter reaction for electron-rich heterocycles, it became
      necessary to develop and apply an unprecedented modification of the venerable
      Horner-Wadsworth-Emmons reaction, employing 2-fluoroethoxyphosphonates that may
      prove to be of general value in organic synthesis. These studies resulted in the
      discovery of some of the most potent epothilones reported to date. Equipped with
      functional groups to accommodate modern drug delivery technologies, some of these
      compounds exhibited picomolar potencies that qualify them as payloads for
      antibody drug conjugates (ADCs), while a number of them revealed impressive
      activities against drug resistant human cancer cells, making them desirable for
      potential medical applications.

PMID- 28513143
TI  - Interactive Effects of Corrosion, Copper, and Chloramines on Legionella and
      Mycobacteria in Hot Water Plumbing.
AB  - Complexities associated with drinking water plumbing systems can result in
      undesirable interactions among plumbing components that undermine engineering
      controls for opportunistic pathogens (OPs). In this study, we examine the effects
      of plumbing system materials and two commonly applied disinfectants, copper and
      chloramines, on water chemistry and the growth of Legionella and mycobacteria
      across a transect of bench- and pilot-scale hot water experiments carried out
      with the same municipal water supply. We discovered that copper released from
      corrosion of plumbing materials can initiate evolution of >1100 times more
      hydrogen (H2) from water heater sacrificial anode rods than does presence of
      copper dosed as soluble cupric ions. H2 is a favorable electron donor for
      autotrophs and causes fixation of organic carbon that could serve as a nutrient
      for OPs. Dosed cupric ions acted as a disinfectant in stratified stagnant pipes,
      inhibiting culturable Legionella and biofilm formation, but promoted Legionella
      growth in pipes subject to convective mixing. This difference was presumably due
      to continuous delivery of nutrients to biofilm on the pipes under convective
      mixing conditions. Chloramines eliminated culturable Legionella and prevented L.
      pneumophila from recolonizing biofilms, but M. avium gene numbers increased by
      0.14-0.76 logs in the bulk water and were unaffected in the biofilm. This study
      provides practical confirmation of past discrepancies in the literature regarding
      the variable effects of copper on Legionella growth, and confirms prior reports
      of trade-offs between Legionella and mycobacteria if chloramines are applied as
      secondary disinfectant residual.

PMID- 28513144
TI  - Rapid Elemental Analysis of Aerosols Using Atmospheric Glow Discharge Optical
      Emission Spectroscopy.
AB  - A new, low-cost approach based on the application of atmospheric radio frequency
      glow discharge (rf-GD) optical emission spectroscopy (OES) has been developed for
      near real-time measurement of multielemental concentration in airborne
      particulate phase. This method involves deposition of aerosol particles on the
      tip of a cathode in a coaxial microelectrode system, followed by ablation,
      atomization, and excitation of the particulate matter using the rf-GD. The
      resulting atomic emissions are recorded using a spectrometer for elemental
      identification and quantification. The glow discharge plasma in our system was
      characterized by measuring spatially resolved gas temperatures (378-1438 K) and
      electron densities (2-5 * 1014 cm-3). Spatial analysis of the spectral features
      showed that the excitation of the analyte occurred in the region near the
      collection electrode. The temporal analysis of spectral features in the rf-GD
      showed that the collected particles were continuously ablated; the time for
      complete ablation of 193 ng of sucrose particles was found to be approximately 2
      s. The system was calibrated using 100 nm particles containing C, Cd, Mn, and Na,
      respectively. The method provides limits of detection in the range of 0.055-1.0
      ng, and a measurement reproducibility of 5-28%. This study demonstrates that the
      rf-GD can be an excellent excitation source for the development of low-cost hand
      held sensors for elemental measurement of aerosols.

PMID- 28513145
TI  - Monodisperse Fiber-like Micelles of Controlled Length and Composition with an
      Oligo(p-phenylenevinylene) Core via "Living" Crystallization-Driven Self
      Assembly.
AB  - We report the preparation of a series of fiber-like micelles of narrow length
      distribution with an oligo(p-phenylenevinylene) (OPV)-core and a poly(N
      isopropylacrylamide) (PNIPAM) corona via two different crystallization-driven
      self-assembly (CDSA) strategies. The average length Ln of these micelles can be
      varied up to 870 nm by varying the temperature in self-seeding experiments. In
      addition, seeded growth was employed not only to prepare uniform micelles of
      controlled length, but also to form fiber-like A-B-A triblock comicelles with an
      OPV-core.

PMID- 28513146
TI  - Insights into Antimony Adsorption on {001} TiO2: XAFS and DFT Study.
AB  - Antimony (Sb) contamination poses an emerging environmental risk, whereas its
      removal remains a contemporary challenge due to the lack of knowledge in its
      surface chemistry and efficient adsorbent. In this study, self-assembly {001}
      TiO2 was examined for its effectiveness in Sb removal, and the molecular level
      surface chemistry was studied with X-ray absorption spectroscopy and density
      functional theory calculations. The kinetics results show that Sb adsorption
      followed the pseudo-second order reaction, and the Langmuir adsorption capacity
      was 200 mg/g for Sb(III) and 156 mg/g for Sb(V). The PZC of TiO2, which was 6.6
      prior to the adsorption experiment, shifted to 4.8 and <0 after adsorption of
      Sb(III) and Sb(V), respectively, indicating the formation of negatively charged
      inner-sphere complexes. EXAFS results suggest that Sb(III/V) adsorption exhibited
      a bidentate binuclear surface complex. The orbital hybridizing of complexes was
      studied by XANES, molecular orbital theory (MO), and density of states (DOS)
      calculations. The change in orbital energy derived from orbital hybridizing of
      adsorbed Sb on surfaces is the driving force underlining the Sb surface
      chemistry. New bonds between Sb and TiO2 surface were formed with matched orbital
      energies. Integrating the molecular and electronic structures into surface
      complexation modeling reveals the nature of macroscopic Sb adsorption behaviors.

PMID- 28513147
TI  - Four Specific Hapten Conformations Dominating Antibody Specificity: Quantitative
      Structure-Activity Relationship Analysis for Quinolone Immunoassay.
AB  - Antibody-based immunoassay methods have been important tools for monitoring drug
      residues in animal foods. However, because of limited knowledge about the
      quantitative structure-activity relationships between a hapten and its resultant
      antibody specificity, antibody production with the desired specificity is still a
      huge challenge. In this study, the three-dimensional quantitative structure
      activity relationship (3D QSAR) was analyzed in accordance with the cross
      reactivity of quinolone drugs reacting with the antibody raised by pipemidic acid
      as the immunizing hapten and compared with the reported cross-reactivity data and
      their hapten structures. It was found that the specificity of a quinolone
      antibody was strongly related to the conformation of the hapten used and that
      hapten conformations shaped like the letters "I", "P", and "Phi" were essential
      for the desired high specificity with low cross-reactivity, but that the hapten
      conformation shaped like the letter "Y" led to an antibody with broad specificity
      and high cross-reactivity. Almost all of the antibodies against quinolones could
      result from these four hapten conformations. It was first found that the concrete
      conformations dominated the specificity of the antibody to quinolone, which will
      be of significance for the accurate hapten design, predictable antibody
      specificity, and better understanding the recognition mechanism between haptens
      and the antibodies for immunoassays.

PMID- 28513148
TI  - Correction to X-ray Absorption Spectroscopic Quantification and Speciation
      Modeling of Sulfate Adsorption on Ferrihydrite Surfaces.

PMID- 28513149
TI  - Vertical Profiles, Sources, and Transport of PFASs in the Arctic Ocean.
AB  - The relative importance of atmospheric versus oceanic transport for poly- and
      perfluorinated alkyl substances (PFASs) reaching the Arctic Ocean is not well
      understood. Vertical profiles from the Central Arctic Ocean and shelf water, snow
      and meltwater samples were collected in 2012; 13 PFASs (C6-C12 PFCAs; C6, 8, 10
      PFSAs; MeFOSAA and EtFOSAA; and FOSA) were routinely detected (range: <5-343
      pg/L). PFASs were only detectable above 150 m depth in the polar mixed layer
      (PML) and halocline. Enhanced concentrations were observed in snow and meltpond
      samples, implying atmospheric deposition as an important source of PFASs. Model
      results suggested atmospheric inputs to account for 34-59% (~11-19 pg/L) of
      measured PFOA concentrations in the PML (mean 32 +/- 15 pg/L). Modeled surface
      and halocline measurements for PFOS based on North Atlantic inflow (11-36 pg/L)
      agreed with measurements (mean, 17, range <5-41 pg/L). Modeled deep water
      concentrations below 200 m (5-15 pg/L) were slightly higher than measurements (<5
      pg/L), suggesting the lower bound of PFAS emissions estimates from wastewater and
      rivers may provide the best estimate of inputs to the Arctic. Despite low
      concentrations in deep water, this reservoir is expected to contain most of the
      PFOS mass in the Arctic (63-180 Mg) and is projected to continue increasing to
      2038.

PMID- 28513150
TI  - Production of Caproic Acid from Mixed Organic Waste: An Environmental Life Cycle
      Perspective.
AB  - Caproic acid is an emerging platform chemical with diverse applications.
      Recently, a novel biorefinery process, that is, chain elongation, was developed
      to convert mixed organic waste and ethanol into renewable caproic acids. In the
      coming years, this process may become commercialized, and continuing to improve
      on the basis of numerous ongoing technological and microbiological studies. This
      study aims to analyze the environmental performance of caproic acid production
      from mixed organic waste via chain elongation at this current, early stage of
      technological development. To this end, a life cycle assessment (LCA) was
      performed to evaluate the environmental impact of producing 1 kg caproic acid
      from organic waste via chain elongation, in both a lab-scale and a pilot-scale
      system. Two mixed organic waste were used as substrates: the organic fraction of
      municipal solid waste (OFMSW) and supermarket food waste (SFW). Ethanol use was
      found to be the dominant cause of environmental impact over the life cycle.
      Extraction solvent recovery was found to be a crucial uncertainty that may have a
      substantial influence on the life-cycle impacts. We recommend that future
      research and industrial producers focus on the reduction of ethanol use in chain
      elongation and improve the recovery efficiency of the extraction solvent.

PMID- 28513151
TI  - Acoustophoretic Mobility and Its Role in Optimizing Acoustofluidic Separations.
AB  - In the separation sciences, sample species are separated according to their
      physicochemical properties, the nature of the selective field, and, if present,
      the properties of the medium in which they are dissolved or suspended.
      Separations may be carried out on a continuous basis in microfluidic devices or
      split-flow thin channel (SPLITT) devices by selectively transporting species in a
      direction transverse to the direction of flow of the suspending fluid. Separation
      is achieved in the so-called transport mode according to relative differences in
      mobility of the species under the influence of the applied field. Gravitational,
      centrifugal, thermal gradient, magnetic, electric, and dielectric fields may all
      be used for continuous SPLITT fractionation. We present here the theory for
      optimizing the operation of the relatively new technique of acoustic SPLITT
      fractionation for the continuous separation of non-Brownian materials. The theory
      is based on a quantitatively defined acoustophoretic mobility that is consistent
      with the generalized concept of mobility proposed by Giddings. Until now,
      acoustophoretic mobility has almost exclusively been used as a qualitative
      descriptor for velocity induced by an acoustic field. The quantitative definition
      presented here will contribute to the advancement of all forms of acoustofluidic
      separations.

PMID- 28513154
TI  - Role of Proton Tunneling and Metal-Free Organocatalysis in the Decomposition of
      Methanediol: A Theoretical Study.
AB  - Canonical variational transition state theory rate calculations have been
      performed to assess the fate of methanediol in the troposphere. The calculations
      suggest that proton tunneling plays a very important role in the gas-phase
      decomposition of methanediol as it enhances the rate of the reaction by 1-9
      orders of magnitude in the tropospherically relevant temperature range of 200-300
      K. The effect of proton tunneling is greatest at 200 K; the rate constant is
      enhanced up to 9 orders of magnitude. This is in stark contrast to previous
      calculations suggesting that tunneling would not play any role in the alkanediol
      decomposition under typical laboratory and interstellar conditions. Furthermore,
      the results imply that though water is the most dominant trace component of the
      troposphere, formic acid and the hydroperoxyl radical, which are relatively less
      abundant, outcompete water in catalyzing the decomposition. Methanediol may also
      catalyze its own decomposition below 280 K. However, this autocatalytic pathway
      turns out to be less effective than the water-catalyzed one. These results may
      play a crucial role in improving our understanding of alkanediol chemistry, which
      has a broad appeal beyond the troposphere.

PMID- 28513153
TI  - Sensitive Analysis of Protein Adsorption to Colloidal Gold by Differential
      Centrifugal Sedimentation.
AB  - It is demonstrated that the adsorption of bovine serum albumin (BSA) to aqueous
      gold colloids can be quantified with molecular resolution by differential
      centrifugal sedimentation (DCS). This method separates colloidal particles of
      comparable density by mass. When proteins adsorb to the nanoparticles, both their
      mass and their effective density change, which strongly affects the sedimentation
      time. A straightforward analysis allows quantification of the adsorbed layer.
      Most importantly, unlike many other methods, DCS can be used to detect
      chemisorbed proteins ("hard corona") as well as physisorbed proteins ("soft
      corona"). The results for BSA on gold colloid nanoparticles can be modeled in
      terms of Langmuir-type adsorption isotherms (Hill model). The effects of surface
      modification with small thiol-PEG ligands on protein adsorption are also
      demonstrated.

PMID- 28513152
TI  - A Molecular Mechanism for Nonphotochemical Quenching in Cyanobacteria.
AB  - The cyanobacterial orange carotenoid protein (OCP) protects photosynthetic
      cyanobacteria from photodamage by dissipating excess excitation energy collected
      by phycobilisomes (PBS) as heat. Dissociation of the PBS-OCP complex in vivo is
      facilitated by another protein known as the fluorescence recovery protein (FRP),
      which primarily exists as a dimeric complex. We used various mass spectrometry
      (MS)-based techniques to investigate the molecular mechanism of this FRP-mediated
      process. FRP in the dimeric state (dFRP) retains its high affinity for the C
      terminal domain (CTD) of OCP in the red state (OCPr). Site-directed mutagenesis
      and native MS suggest the head region on FRP is a candidate to bind OCP. After
      attachment to the CTD, the conformational changes of dFRP allow it to bridge the
      two domains, facilitating the reversion of OCPr into the orange state (OCPo)
      accompanied by a structural rearrangement of dFRP. Interestingly, we found a
      mutual response between FRP and OCP; that is, FRP and OCPr destabilize each
      other, whereas FRP and OCPo stabilize each other. A detailed mechanism of FRP
      function is proposed on the basis of the experimental results.

PMID- 28513155
TI  - Degradation Kinetics of 6'''-p-Coumaroylspinosin and Identification of Its
      Metabolites by Rat Intestinal Flora.
AB  - 6'''-p-Coumaroylspinosin (P-CS), a bioactive flavonoid, is typically extracted
      from Semen Ziziphi Spinosae (SZS). In this study, a high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to
      determine P-CS for investigating the degradation characteristics of P-CS
      incubated with rat feces. The results showed that P-CS degraded rapidly and the
      degradation speeds varied depending upon the P-CS concentrations (3, 15, and 30
      MUg/mL). The degradation of P-CS processes follow first-order kinetics. On the
      basis of the mass spectrometry (MS) spectrum mode of the product ions, two main
      metabolites of P-CS were identified. Swertisin was the main metabolite at 3 and
      15 MUg/mL, while spinosin was produced when the P-CS concentration was 30 MUg/mL.
      Spinosin and swertisin could improve mRNA transcription levels of glutamate
      receptor K1, K2, and K3 (GluK1, GluK2, and GluK3) subunits in rat hippocampal
      neurons. In addition, they showed an obvious synergistic effect in this respect.
      Collectively, the results can be used to explain the metabolic and
      pharmacological mechanisms of P-CS.

PMID- 28513156
TI  - Quantum Chemical Investigation on Photochemical Reactions of Nonanoic Acids at
      Air-Water Interface.
AB  - Photoinduced chemical reactions of organic compounds at the marine boundary layer
      have recently attracted significant experimental attention because this kind of
      photoreactions has been proposed to have substantial impact on local new particle
      formation and their photoproducts could be a source of secondary organic
      aerosols. In this work, we have employed first-principles density functional
      theory method combined with cluster models to systematically explore
      photochemical reaction pathways of nonanoic acids (NAs) to form volatile
      saturated and unsaturated C9 and C8 aldehydes at air-water interfaces. On the
      basis of the results, we have found that the formation of C9 aldehydes is not
      initiated by intermolecular Norrish type II reaction between two NAs but by
      intramolecular T1 C-O bond fission of NA generating acyl and hydroxyl radicals.
      Subsequently, saturated C9 aldehydes are formed through hydrogenation reaction of
      acyl radical by another intact NA. Following two dehydrogenation reactions,
      unsaturated C9 aldehydes are generated. In parallel, the pathway to C8 aldehydes
      is initiated by T1 C-C bond fission of NA, which generates octyl and carboxyl
      radicals; then, an octanol is formed through recombination reaction of octyl with
      hydroxyl radical. In the following, two dehydrogenation reactions result into an
      enol intermediate from which saturated C8 aldehydes are produced via NA-assisted
      intermolecular hydrogen transfer. Finally, two dehydrogenation reactions generate
      unsaturated C8 aldehydes. In these reactions, water and NA molecules are found to
      play important roles. They significantly reduce relevant reaction barriers. Our
      work has also explored oxygenation reactions of NA with molecular oxygen and
      radical-radical dimerization reactions.

PMID- 28513157
TI  - Shedding Light on the Accuracy of Optimally Tuned Range-Separated Approximations
      for Evaluating Oxidation Potentials.
AB  - There is a surge in the literature on the development of exchange-correlation
      density functionals for a wide variety of physical and chemical properties. As a
      recent endeavor toward the systematic and nonempirical design of density
      functional approximations, optimally tuned range-separated hybrid (OT-RSH) models
      have been introduced. In this work, we propose novel OT-RSH density functionals
      for predicting the oxidation potentials of organic compounds from different
      categories. In this regard, detailed analysis of the role of nonempirical
      optimization of the range separation parameter and importance of short- and long
      range exact-like exchange in OT-RSH calculations of the oxidation potential has
      also been done. It is shown that the newly developed OT-RSH approximations not
      only perform better than other standard long-range corrected functionals but also
      in many cases outperform other conventional hybrid functionals with a fixed
      amount of exact-like exchange. Plus, we find that the proposed functionals
      describe well the oxidation potentials of compounds for which the tuning of the
      range separation parameter was not performed. From a different perspective,
      accountability of the computed frontier orbital energies from the OT-RSH density
      functionals for estimation of oxidation potentials has also been evaluated. Our
      results reveal that the negative highest occupied molecular orbital energies of
      molecules and the negative lowest unoccupied molecular orbital energies of their
      cations correlate remarkably with the observed oxidation potentials. Admittedly,
      with more efforts along this line, modern OT-RSH functionals with broader
      applicability can be released for computational electrochemistry.

PMID- 28513158
TI  - Molecular Optimization Enables over 13% Efficiency in Organic Solar Cells.
AB  - A new polymer donor (PBDB-T-SF) and a new small molecule acceptor (IT-4F) for
      fullerene-free organic solar cells (OSCs) were designed and synthesized. The
      influences of fluorination on the absorption spectra, molecular energy levels,
      and charge mobilities of the donor and acceptor were systematically studied. The
      PBDB-T-SF:IT-4F-based OSC device showed a record high efficiency of 13.1%, and an
      efficiency of over 12% can be obtained with a thickness of 100-200 nm, suggesting
      the promise of fullerene-free OSCs in practical applications.

PMID- 28513159
TI  - Accurate Anharmonic Zero-Point Energies for Some Combustion-Related Species from
      Diffusion Monte Carlo.
AB  - Full-dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ
      calculations have been determined for 48 small combustion-related molecules. The
      analytic surfaces have been used in Diffusion Monte Carlo calculations of the
      anharmonic zero-point energies. The resulting anharmonicity corrections are
      compared to vibrational perturbation theory results based both on the same level
      of electronic structure theory and on lower-level electronic structure methods
      (B3LYP and MP2).

PMID- 28513160
TI  - Formation of Free and Protein-Bound Heterocyclic Amines in Roast Beef Patties
      Assessed by UPLC-MS/MS.
AB  - The effect of different roasting temperatures on the amounts of 17 heterocyclic
      amines (HAs) from seven categories of both free and protein-bound states in roast
      beef patties was assessed using an ultraperformance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) method. There were increased amounts and more
      types of HAs detected at higher roasting temperatures. Nine free HAs were
      detected at 250  degrees C, including PhIP (14.34 +/- 0.36 ng/g), DMIP (1.02 +/-
      0.07 ng/g), 1,5,6-TMIP (1.70 +/- 0.08 ng/g), MeIQ (0.36 +/- 0.01 ng/g), IQx (0.37
      +/- 0.04 ng/g), MeIQx (9.94 +/- 0.61 ng/g), 4,8-DiMeIQx (0.90 +/- 0.05 ng/g),
      norharman (6.03 +/- 0.30 ng/g), and harman (2.60 +/- 0.09 ng/g). Also, 37.32 ng/g
      of total free HAs was generated. Twelve protein-bound HAs were detected in roast
      beef patties at 250  degrees C, including PhIP (1.70 +/- 0.13 ng/g), DMIP (2.33
      +/- 0.25 ng/g), 1,5,6-TMIP (3.62 +/- 0.49 ng/g), MeIQ (5.47 +/- 0.18 ng/g),
      IQ[4,5-b] (0.70 +/- 0.03 ng/g) MeIQx (4.03 +/- 0.41 ng/g), 4,8-DiMeIQx (0.67 +/-
      0.09 ng/g), MeAalphaC (19.51 +/- 1.12 ng/g), AalphaC (2.91 +/- 0.45 ng/g),
      norharman (1304.96 +/- 110.73 ng/g), harman (400.85 +/- 25.29 ng/g), and Phe-P-1
      (0.81 +/- 0.06 ng/g). The highest amount of protein-bound HAs was 2913.31 ng/g at
      175  degrees C. PhIP tended to exist in a free state, whereas MeIQ, harman, and
      norharman tended to exist in a protein-bound state. Furthermore, Phe-P-1,
      MeAalphaC, and AalphaC were detected only in a protein-bound state. These results
      could be useful for evaluating the exposure to HAs in a daily diet.

PMID- 28513162
TI  - Radical C-H Fluorination Using Unprotected Amino Acids as Radical Precursors.
AB  - We report a unique example of utilizing unprotected amino acids for benzylic C-H
      fluorination via a radical process. alpha-Aminoalkyl radicals are readily
      generated via oxidative decarboxylation of unprotected amino acids using a simple
      silver(I) catalyst and Selectfluor, which serves as both a mild oxidant and
      source of electrophilic fluorine. Mechanistic investigation shows that
      coordination of the unprotected amino acid plays a crucial role in lowering the
      oxidation potential of Ag(I), enabling oxidation under mild conditions. Mono- or
      difluorination is possible by controlling the stoichiometry of amino acid and
      fluorine source.

PMID- 28513161
TI  - Improved Synthesis for Modular Ascarosides Uncovers Biological Activity.
AB  - A versatile synthesis of modular ascarosides, a family of signaling molecules
      from Caenorhabditis elegans and other nematodes, via hydrogenolysis of a cyclic
      sulfate derived from methyl-alpha-l-rhamnopyranoside is reported. The route
      enables selective introduction of different side chains at the 1, 2, and 4
      positions of the sugar, as demonstrated for ascarosides from C. elegans and
      Pristionchus pacificus. Bioassays with synthetic samples of 4'-tigloyl ascaroside
      mbas#3 revealed its role as an avoidance or dispersal signal.

PMID- 28513163
TI  - Bronsted Base Mediated Stereoselective Diphosphination of Terminal Alkynes with
      Diphosphanes.
AB  - A Bronsted base mediated stereoselective diphosphination of terminal alkynes with
      diphosphanes proceeds to deliver the corresponding (E)-1,2-diphosphinoethenes in
      good yields. The reaction of aromatic alkynes occurs efficiently in the presence
      of a catalytic amount of LiO-t-Bu while MN(TMS)2 (M = Li or Na) gave better
      results in the case of aliphatic substrates. The Bronsted base mediated protocol
      can offer a good alternative to precedented transition-metal-catalyzed or radical
      promoted approaches to the 1,2-diphosphinoethene framework of potent interest in
      catalysis and coordination chemistry.

PMID- 28513164
TI  - Total Synthesis of Neomarchantin A: Key Bond Constructions Performed Using
      Continuous Flow Methods.
AB  - A synthesis of neomarchantin A has been achieved wherein key bond constructions
      involving C-O or C-C bond formations were augmented via continuous flow
      techniques. Of note, the synthesis of neomarchantin A represents the first
      demonstration of catalytic macrocyclic olefin metathesis as a key step for the
      synthesis of a macrocyclic bisbibenzyl natural product.

PMID- 28513165
TI  - alpha-CASSCF: An Efficient, Empirical Correction for SA-CASSCF To Closely
      Approximate MS-CASPT2 Potential Energy Surfaces.
AB  - Because of its computational efficiency, the state-averaged complete active-space
      self-consistent field (SA-CASSCF) method is commonly employed in nonadiabatic ab
      initio molecular dynamics. However, SA-CASSCF does not effectively recover
      dynamical correlation. As a result, there can be qualitative differences between
      SA-CASSCF potential energy surfaces (PESs) and more accurate reference surfaces
      computed using multistate complete active space second-order perturbation theory
      (MS-CASPT2). Here we introduce an empirical correction to SA-CASSCF that scales
      the splitting between individual states and the state-averaged energy. We call
      this the alpha-CASSCF method, and we show here that it significantly improves the
      accuracy of relative energies and PESs compared with MS-CASPT2 for the
      chromophores of green fluorescent and photoactive yellow proteins. As such, this
      method may prove to be quite valuable for nonadiabatic dynamics.

PMID- 28513166
TI  - Bronsted Acid Catalyzed Nitrile Synthesis from Aldehydes Using Oximes via
      Transoximation at Ambient Temperature.
AB  - The Bronsted acid-catalyzed synthesis of nitriles is described via transoximation
      under mild conditions using an O-protected oxime as a more stable equivalent of
      explosive O-protected hydroxylamines. The nitrile was generated via an O
      protected aldoxime produced from the aldehyde and an O-protected oxime through
      transoximation. The reaction could be performed on a 1 g scale.

PMID- 28513168
TI  - Influence of Rotator Design on the Speed of Self-Assembled Four-Component
      Nanorotors: Coordinative Versus Dispersive Interactions.
AB  - Four-component nanorotors are prepared by the self-assembly of stator [Cu4(4)]4+
      with its four copper(I)-loaded phenanthroline stations and various rotators
      carrying one, two, or three pyridine terminals. The fourth component, 1,4
      diazabicyclo[2.2.2]octane, serves as a connecting axle between rotator and
      stator. Capitalizing on the heteroleptic pyridyl and phenanthroline metal
      complexes concept, the rotator's pyridine terminals are connected to the
      copper(I)-loaded phenanthroline stations (Npy -> [Cu(phen)]+) in the STOP state
      and disconnected in the transition state of rotation. As the barrier of the
      thermally activated rotation, measured by variable-temperature 1H NMR, is mainly
      governed by attractive forces between stator stations and rotator terminals, it
      increases along the series Ea (monopyridine rotator) < Ea (dipyridine rotator) <
      Ea (tripyridine rotator). However, there are even distinct differences in rate
      between rotors with equal number of rotator terminals. The change from the 5,10
      dipyridyl (cis) to 5,15-dipyridyl (trans) zinc porphyrin rotator enhances the
      rotational frequency by almost 1000-fold. Density functional theory computational
      results suggest that not only coordinative Npy -> [Cu(phen)]+ interactions but
      also dispersive attraction influence the barrier of rotation.

PMID- 28513169
TI  - Structural and Magnetic Properties of the Osmium Double Perovskites Ba2
      xSrxYOsO6.
AB  - The crystal and magnetic structures of double perovskites of the type Ba2
      xSrxYOsO6 were studied by synchrotron X-ray and neutron powder diffraction
      methods, bulk magnetic susceptibility measurements, and X-ray absorption
      spectroscopy. The structures were refined using combined neutron and synchrotron
      data sets based on an ordered array of corner-sharing YO6 and OsO6 octahedra,
      with the Ba/Sr cations being completely disordered. The structure evolves from
      cubic to monoclinic Fm3m (x ~ 0.6) -> I4/m (x ~ 1.0) -> I2/m (x ~ 1.6) -> P21/n
      as the Sr content is increased, due to the introduction of cooperative tilting of
      the octahedra. Bulk magnetic susceptibility measurements demonstrate the oxides
      are all anti-ferromagnets. The decrease in symmetry results in a nonlinear
      increase in the Neel temperature. Low-temperature neutron diffraction
      measurements of selected examples show these to be type-I anti-ferromagnets. X
      ray absorption spectra collected at the Os L3- and L2-edges confirm the Os is
      pentavalent in all cases, and there is no detectable change in the covalency of
      the Os cation as the A-cation changes. Analysis of the L3/L2 branching ratio
      shows that the spin-orbit coupling is constant and insignificant across the
      series.

PMID- 28513167
TI  - Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of
      Monocarboxylate Transporter 6.
AB  - Monocarboxylate transporter 6 (MCT6; SLC16A5) has been recognized for its role as
      a xenobiotic transporter, with characterized substrates probenecid, bumetanide,
      and nateglinide. To date, the impact of commonly ingested dietary compounds on
      MCT6 function has not been investigated, and therefore, the objective of this
      study was to evaluate a variety of flavonoids for their potential MCT6-specific
      interactions. Flavonoids are a large group of polyphenolic phytochemicals found
      in commonly consumed plant-based products that have been recognized for their
      dietary health benefits. The uptake of bumetanide in human MCT6 gene-transfected
      Xenopus laevis oocytes was significantly decreased in the presence of a variety
      of flavonoids (e.g., quercetin, luteolin, phloretin, and morin), but was not
      significantly affected by flavonoid glycosides (e.g., naringin, rutin,
      phlorizin). The IC50 values of quercetin, phloretin, and morin were determined to
      be 25.3 +/- 3.36, 17.3 +/- 2.37, and 33.1 +/- 3.29 MUM, respectively. The
      mechanism of inhibition of phloretin was reversible and competitive, with a Ki
      value of 22.8 MUM. Furthermore, typical MCT substrates were also investigated for
      their potential interactions with MCT6. Substrates of MCTs 1, 2, 4, 8, and 10 did
      not cause any significant decrease in MCT6-mediated bumetanide uptake, suggesting
      that MCT6 has distinct compound selectivity. In summary, these results suggest
      that dietary aglycon flavonoids may significantly alter the pharmacokinetics and
      pharmacodynamics of bumetanide and other MCT6-specific substrates, and may
      represent potential substrates for MCT6.

PMID- 28513170
TI  - Phospholipid-Biomimetic Fluorescent Mitochondrial Probe with Ultrahigh
      Selectivity Enables In Situ and High-Fidelity Tissue Imaging.
AB  - In situ and directly imaging mitochondria in tissues instead of isolated cells
      can offer more native and accurate information. Particularly, in the clinical
      diagnose of mitochondrial diseases such as mitochondrial myopathy, it is a
      routine examination item to directly observe mitochondrial morphology and number
      in muscle tissues from patients. However, it is still a challenging task because
      the selectivity of available probes is inadequate for exclusively tissue imaging.
      Inspired by the chemical structure of amphiphilic phospholipids in mitochondrial
      inner membrane, we synthesized a phospholipid-biomimetic amphiphilic fluorescent
      probe (Mito-MOI) by modifying a C18-alkyl chain to the lipophilic side of
      carbazole-indolenine cation. Thus, the phospholipid-like Mito-MOI locates at
      mitochondrial inner membrane through electrostatic interaction between its cation
      and inner membrane negative charge. Simultaneously, the C18-alkyl chain, as the
      second targeting group, is deeply embedded into the hydrophobic region of inner
      membrane through hydrophobic interaction. Therefore, the dual targeting groups
      (cation and C18-alkyl chain) actually endow Mito-MOI with ultrahigh selectivity.
      As expected, high-resolution microscopic photos showed that Mito-MOI indeed
      stained mitochondrial inner membrane. Moreover, in situ and high-fidelity tissue
      imaging has been achieved, and particularly, four kinds of mitochondria and their
      crystal-like structure in muscle tissues were visualized clearly. Finally, the
      dynamic process of mitochondrial fission in living cells has been shown. The
      strategy employing dual targeting groups should have reference value for
      designing fluorescent probes with ultrahigh selectivity to various intracellular
      membranous components.

PMID- 28513171
TI  - Ni(II) Complexes of the Redox-Active Bis(2-aminophenyl)dipyrrin: Structural,
      Spectroscopic, and Theoretical Characterization of Three Members of an Electron
      Transfer Series.
AB  - The sterically hindered bis(2-aminophenyl)dipyrrin ligand H3NL was prepared. X
      ray diffraction discloses a bifurcated hydrogen bonding network involving the
      dipyrrin and one aniline ring. The reaction of H3NL with one equivalent of
      nickel(II) in the air produces a paramagnetic neutral complex, which absorbs
      intensively in the Vis-NIR region. Its electron paramagnetic resonance spectrum
      displays resonances at g1 = 2.033, g2 = 2.008, and g3 = 1.962 that are
      reminiscent of an (S = 1/2) system having a predominant organic radical
      character. Both the structural investigation (X-ray diffraction) and density
      functional theory calculations on [NiII(NL*)] points to an unprecedented mixed
      "pyrrolyl-anilinyl" radical character. The neutral complex [NiII(NL*)] exhibits
      both a reversible oxidation wave at -0.28 V vs Fc+/Fc and a reversible reduction
      wave at -0.91 V. The anion was found to be highly air-sensitive, but could be
      prepared by reduction with cobaltocene and structurally characterized. It
      comprises a Ni(II) ion coordinated to a closed-shell trianionic ligand and hence
      can be formulated as [NiII(NL)]-. The cation was generated by reacting
      [NiII(NL*)] with one equivalent of silver hexafluoroantimonate. By X-ray
      diffraction we established that it contains an oxidized, closed-shell ligand
      coordinated to a nickel(II) ion. We found that a reliable hallmark for both the
      oxidation state of the ligand and the extent of delocalization within the series
      is the bond connecting the dipyrrin and the aniline, which ranges between 1.391 A
      (cation) and 1.449 A (anion). The cation and anion exhibit a rich Vis-NIR
      spectrum, despite their nonradical nature. The low energy bands correspond to
      ligand-based electronic excitations. Hence, the HOMO-LUMO gap is small, and the
      redox processes in the electron transfer series are exclusively ligand-centered.

PMID- 28513172
TI  - A Quantum Chemical Interpretation of Two-Dimensional Electronic Spectroscopy of
      Light-Harvesting Complexes.
AB  - Nonlinear electronic spectroscopies represent one of the most powerful techniques
      to study complex multichromophoric architectures. For these systems, in fact,
      linear spectra are too congested to be used to disentangle the many coupled
      vibroelectronic processes that are activated. By using a 2D approach, instead, a
      clear picture can be achieved, but only when the recorded spectra are combined
      with a proper interpretative model. So far, this has been almost always achieved
      through parametrized exciton Hamiltonians that necessarily introduce biases
      and/or arbitrary assumptions. In this study, a first-principles approach is
      presented that combines accurate quantum chemical descriptions with state-of-the
      art models for the environment through the use of atomistic and polarizable
      embeddings. Slow and fast bath dynamics, along with exciton transport between the
      pigments, are included. This approach is applied to the 2DES spectroscopy of the
      Light-Harvesting 2 (LH2) complex of purple bacteria. Simulations are extended
      over the entire visible-near-infrared spectral region to cover both carotenoid
      and bacteriochlorophyll signals. Our results provide an accurate description of
      excitonic properties and relaxation pathways, and give an unprecedented insight
      into the interpretation of the spectral signatures of the measured 2D signals.

PMID- 28513173
TI  - Photophysics of Deoxycytidine and 5-Methyldeoxycytidine in Solution: A
      Comprehensive Picture by Quantum Mechanical Calculations and Femtosecond
      Fluorescence Spectroscopy.
AB  - The study concerns the relaxation of electronic excited states of the DNA
      nucleoside deoxycytidine (dCyd) and its methylated analogue 5-methyldeoxycytidine
      (5mdCyd), known to be involved in the formation of UV-induced lesions of the
      genetic code. Due to the existence of four closely lying and potentially coupled
      excited states, the deactivation pathways in these systems are particularly
      complex and have not been assessed so far. Here, we provide a complete
      mechanistic picture of the excited state relaxation of dCyd/5mdCyd in three
      solvents-water, acetonitrile, and tetrahydrofuran-by combining femtosecond
      fluorescence experiments, addressing the effect of solvent proticity on the
      relaxation dynamics of dCyd and 5mdCyd for the first time, and two complementary
      quantum mechanical approaches (CASPT2/MM and PCM/TD-CAM-B3LYP). The lowest energy
      pipi* state is responsible for the sub-picosecond lifetime observed for dCyd in
      all the solvents. In addition, computed excited state absorption and transient IR
      spectra allow one, for the first time, to assign the tens of picoseconds time
      constant, reported previously, to a dark state (nOpi*) involving the carbonyl
      lone pair. A second low-lying dark state, involving the nitrogen lone pair
      (nNpi*), does significantly participate in the excited state dynamics. The 267 nm
      excitation of dCyd leads to a non-negligible population of the second bright
      pipi* state, which affects the dynamics, acting mainly as a "doorway" state for
      the nOpi* state. The solvent plays a key role governing the interplay between the
      different excited states; unexpectedly, water favors population of the dark
      states. In the case of 5mdCyd, an energy barrier present on the main nonradiative
      decay route explains the 6-fold lengthening of the excited state lifetime
      compared to that of dCyd, observed for all the examined solvents. Moreover, C5
      methylation destabilizes both nOpi* and nNpi* dark states, thus preventing them
      from being populated.

PMID- 28513174
TI  - Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti
      inflammatory and Anticolitis Effects of Curcumin.
AB  - Curcumin, a dietary compound from turmeric, has beneficial effects on
      inflammatory diseases such as inflammatory bowel disease. Most previous studies
      have focused on the structure-activity relationship of the thiol-reactive
      alpha,beta-unsaturated carbonyl groups of curcumin, so little is known about the
      roles of methoxy groups in biological activities of curcumin. Here we synthesized
      a series of curcumin analogues with different substitution groups (R = H-, Br-,
      Cl-, F-, NO2-, CH3-, and OH-) to replace the methoxy group and evaluated their
      biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 MUM)
      suppressed 74.91 +/- 0.88, 77.75 +/- 0.89, and 71.75 +/- 0.90% of LPS-induced NO
      production, respectively (P < 0.05). Similarly, these compounds also decreased
      iNOS expression, COX-2 expression, and NF-kappaB signaling in RAW 264.7
      macrophage cells (P < 0.05). However, other analogues, especially Cur-NO2, were
      inactive (P > 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse
      model, the Cur-Br analogue also showed a beneficial effect the same as curcumin
      (P < 0.05), whereas the Cur-NO2 analogue had no effect in the animal model (P >
      0.05). Together, the analogues have dramatically different effects on
      inflammation, supporting that the substitution group on the methoxy position
      plays an important role in the anti-inflammatory effects of curcumin. The methoxy
      group is a potential structural candidate for modification to design curcumin
      based drugs for inflammatory diseases.

PMID- 28513175
TI  - Effect of VOC Emissions from Vegetation on Air Quality in Berlin during a
      Heatwave.
AB  - The potential of emissions from urban vegetation combined with anthropogenic
      emissions to produce ozone and particulate matter has long been recognized. This
      potential increases with rising temperatures and may lead to severe problems with
      air quality in densely populated areas during heat waves. Here, we investigate
      how heat waves affect emissions of volatile organic compounds from urban/suburban
      vegetation and corresponding ground-level ozone and particulate matter. We use
      the Weather Research and Forecasting Model with atmospheric chemistry (WRF-Chem)
      with emissions of volatile organic compounds (VOCs) from vegetation simulated
      with MEGAN to quantify some of these feedbacks in Berlin, Germany, during the
      heat wave in 2006. The highest ozone concentration observed during that period
      was ~200 MUg/m3 (~101 ppbV). The model simulations indicate that the contribution
      of biogenic VOC emissions to ozone formation is lower in June (9-11%) and August
      (6-9%) than in July (17-20%). On particular days within the analyzed heat wave
      period, this contribution increases up to 60%. The actual contribution is
      expected to be even higher as the model underestimates isoprene concentrations
      over urban forests and parks by 0.6-1.4 ppbv. Our study demonstrates that
      biogenic VOCs can considerably enhance air pollution during heat waves. We
      emphasize the dual role of vegetation for air quality and human health in cities
      during warm seasons, which is removal and lessening versus enhancement of air
      pollution. The results of our study suggest that reduction of anthropogenic
      sources of NOx, VOCs, and PM, for example, reduction of the motorized vehicle
      fleet, would have to accompany urban tree planting campaigns to make them really
      beneficial for urban dwellers.

PMID- 28513177
TI  - Hydrogen Bonded Structures of Confined Water Molecules and Electric Field Induced
      Shift of Their Equilibrium Revealed by IR Electroabsorption Spectroscopy.
AB  - Water confined on a nanometer scale plays an essential role in various chemical
      and biological processes. Confined water molecules are often exposed to electric
      fields as manifested by those that occur on protein surfaces or in electrical
      double layers, but the electric field effects on confined water are not fully
      understood. We used IR electroabsorption (EA) spectroscopy with unprecedented
      sensitivity to observe electric-field-induced changes in the OH stretching
      absorption of water (H2O) molecules dissolved in 1,4-dioxane, which constitute a
      simple model system for confined water. A multivariate curve resolution analysis
      of the normal IR spectra (without an electric field) of water in 1,4-dioxane at
      different concentrations indicates the presence of the monomer and dimer of the
      confined water molecules and equilibrium between them. We find that the IR EA
      spectrum that is free from the contribution of field-induced molecular
      reorientation is mainly attributable to a field-induced shift of the equilibrium
      toward the dimer. This result demonstrates a possible control of the polarity of
      confined water by simply applying an external electric field and the ability of
      our method to elucidate how it is achieved.

PMID- 28513176
TI  - Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst
      33258 Derived Mono- and Bisbenzimidazoles.
AB  - A series of Hoechst 33258 based mono- and bisbenzimidazoles have been synthesized
      and their Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA
      duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with
      alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition
      properties with IC50 values <5.0 MUM. Several bisbenzimidazoles (3, 6, 7, 8) also
      inhibit RNA topoisomerase activity of E. coli DNA topoisomerase I.
      Bisbenzimidazoles inhibit bacterial growth much better than monobenzimidazoles
      for Gram-positive strains. The minimum inhibitory concentration (MIC) was much
      lower for Gram positive bacteria (Enterococcus spp. and Staphylococcus spp.,
      including two MRSA strains 0.3-8 MUg/mL) than for the majority of Gram negative
      bacteria (Pseudomonas aeruginosa, 16-32 MUg/mL, Klebsiella pneumoniae > 32
      MUg/mL). Bisbenzimidazoles showed varied stabilization of B-DNA duplex (1.2-23.4 
      degrees C), and cytotoxicity studies show similar variation dependent upon the
      side chain length. Modeling studies suggest critical interactions between the
      inhibitor side chain and amino acids of the active site of DNA topoisomerase I.

PMID- 28513178
TI  - Decoupling the Effects of Mass Density and Hydrogen-, Oxygen-, and Aluminum-Based
      Defects on Optoelectronic Properties of Realistic Amorphous Alumina.
AB  - The search for functional materials is currently hindered by the difficulty to
      find significant correlation between constitutive properties of a material and
      its functional properties. In the case of amorphous materials, the diversity of
      local structures, chemical composition, impurities and mass densities makes such
      a connection difficult to be addressed. In this Letter, the relation between
      refractive index and composition has been investigated for amorphous AlOx
      materials, including nonstoichiometric AlOx, emphasizing the role of structural
      defects and the absence of effect of the band gap variation. It is found that the
      Newton-Drude (ND) relation predicts the refractive index from mass density with a
      rather high level of precision apart from some structures displaying structural
      defects. Our results show especially that O- and Al-based defects act as additive
      local disturbance in the vicinity of band gap, allowing us to decouple the mass
      density effects from defect effects (n = n[ND] + Deltandefect).

PMID- 28513179
TI  - Consumption of Watermelon Juice Enriched in l-Citrulline and Pomegranate
      Ellagitannins Enhanced Metabolism during Physical Exercise.
AB  - l-Citrulline is a nonessential amino acid precursor of arginine and indirectly a
      precursor of nitric oxide (NO), which is a vasodilator and increases
      mitochondrial respiration. On the other hand, the antioxidant pomegranate
      ellagitannins are precursors of urolithin A, which has been associated with
      mitophagy and increased muscle function. To elucidate if a single dose of
      watermelon enrichment with these compounds could have a positive effect after
      high-intensity exercise (eight sets of eight repetitions of half-squat exercise),
      a double-blind randomized crossover in vivo study was performed in healthy male
      subjects (n = 19). Enrichment juices maintained basal levels of blood markers of
      muscle damage, such as lactate dehydrogenase and myoglobin, and showed a
      significant maintenance of force during the exercise and a significant decrease
      in the rating of perceived exertion and muscle soreness after exercise. A
      positive effect was observed between l-citrulline and ellagitannins, improving
      the ergogenic effect of watermelon juice.

PMID- 28513180
TI  - Infrared Spectra of Neutral Bent Carbon Dioxide.
AB  - A combined ab initio and quantum dynamical study characterizes a family of bent
      neutral carbon dioxide molecules in terms of their vibrational levels, electric
      dipole moment surfaces, and infrared spectra in the gas phase. The considered
      isomers include the dioxiranylidene form of CO2 with the equilibrium valence
      angle of 72 degrees , belonging to the ground electronic state, and four open
      structures with the valence angles of 118 degrees /119 degrees  (they belong to
      the singlet and triplet electronic states 21A' and 13A', respectively) and 127
      degrees /128 degrees  (states 11A" and 13A", respectively). All studied bent
      structures possess permanent dipole moments. For all isomers, the antisymmetric
      stretch fundamental is the strongest infrared transition. Individual bent
      molecules can be distinguished on the basis of strong absorption bands in the
      frequency window 1100-1800 cm-1 as well as isotopic shifts in the progression of
      antisymmetric stretch mode. Excitation of bent neutral carbon dioxide near a
      perfect metal surface is also briefly discussed. It is argued that the excitation
      energy from the linear ground state exhibits a substantial red shift depending on
      the molecule-metal distance.

PMID- 28513181
TI  - Synthesis of [8]Cycloparaphenylene-octacarboxylates via Rh-Catalyzed Stepwise
      Cross-Alkyne Cyclotrimerization.
AB  - The synthesis of C4- and C2-symmetrical [8]cycloparaphenylene (CPP)
      octacarboxylates has been achieved via macrocyclization by the rhodium-catalyzed
      intermolecular stepwise cross-cyclotrimerization and subsequent reductive
      aromatization. The C4-symmetrical octa-tert-butyl [8]CPP-octacarboxylate forms a
      dimer in which eight ester moieties face each other. The dimers are aligned so as
      to make a one-dimensional column with a channel structure inside. Both absorption
      and fluorescence maxima of [8]CPP-octacarboxylates in CHCl3 were significantly
      blue-shifted compared to those of [8]CPP due to the presence of eight electron
      withdrawing ester moieties.

PMID- 28513182
TI  - 'It just opens up their world': autism, empathy, and the therapeutic effects of
      equine interactions.
AB  - Experiences of autism-spectrum disorder are now increasingly studied by social
      scientists. Human-animal relations have also become a major focus of social
      inquiry in recent years. Examining horse-assisted therapy for autistic spectrum
      disorders, this is the first paper that brings these fields together. Drawing on
      participant observation and interviews at a UK horse therapy Centre, this article
      examines how staff and the parents of riders account for the successes and
      limitations of equine therapy. To the respondents, horses 'open up' autistic
      children and make possible interactions that seemed impossible before. Horses
      were regarded as facilitating the emergence of apparently social behaviours,
      which included eye contact, pointing, and speech. Three key explanations emerged
      for therapeutic success: the sensorial, embodied experience of riding the horse;
      the specific movements and rhythms of the horse; and, the 'personality' of the
      horse. Equine therapy can be regarded as enabling a form of multispecies
      intersubjectivity, with the resonance between rider and horse seeming to make
      possible a new attunement between humans. Practices of equine therapy, and
      perceptions of its efficacy, serve in turn to attune social scientists to a
      version of empathy constituted through lively and sensorial interactions, as
      opposed to one that is restricted to particular kinds of humans.

PMID- 28513183
TI  - Design and statistical analysis of method transfer studies for biotechnology
      products.

PMID- 28513185
TI  - Moderate dementia: relational social engagement (RSE) during family visits.
AB  - OBJECTIVE: This qualitative study seeks evidence of retained social awareness in
      individuals with moderate dementia residing in care-homes, when engaged in
      interactive family visits. METHOD: Speech/non-speech data collected from 10/15
      minute video-recorded family interactions of five family groups (12 individuals;
      2 sessions per family group) were coded using thematic analysis. RESULTS:
      Interactional patterns embedded in familiar bonds provided the context for the
      superordinate theme: relational social engagement (RSE). This overarched two
      subthemes: in-step and out-of-step; highlighting that RSE, can occur as a result
      of both positive and negative familial communication patterns. When familial
      communication was in-step, despite changed communication pathways, the resident's
      attempts at social engagement appeared open, relaxed, and responsive. A sense of
      trust, and familiarity appeared to facilitate reciprocal understanding and the
      striving of resident family members to retain family group membership. When
      familial communication was out-of-step, active attempts at reciprocity or open
      engagement from visiting family members were not observed. At such times,
      communication became discordant, and frustrated in their efforts to remain an
      integral part of the family group, the resident appeared disinterested or guarded
      often retorting with annoyance at visiting family members. CONCLUSION: The
      construct of RSE appears specific to prior meaningful relationships, where
      optimal social awareness and communication, positive and negative, can occur.
      Currently, dementia assessment and care does not include RSE during family
      interactions. Implications are discussed.

PMID- 28513186
TI  - Initially intact neural responses to pain in autism are diminished during
      sustained pain.
AB  - Pain assessments typically depend on self-report of the pain experience. Yet, in
      individuals with autism spectrum disorders, this can be an unreliable due to
      communication difficulties. Importantly, observations of behavioral hypo- and
      hyperresponsivity to pain suggest altered pain sensitivity in autism spectrum
      disorder. Neuroimaging may provide insight into mechanisms underlying pain
      behaviors. The neural pain signature reliably responds to painful stimulation and
      is modulated by other outside regions, affecting the pain experience. In this
      first functional magnetic resonance imaging study of pain in autism spectrum
      disorder, we investigated neural responses to pain in 15 adults with autism
      spectrum disorder relative to a typical comparison group (n = 16). We explored
      temporal and spatial properties of the neural pain signature and its modulators
      during sustained heat pain. The two groups had indistinguishable pain ratings and
      neural pain signature responses during acute pain; yet, we observed strikingly
      reduced neural pain signature response in autism spectrum disorder during
      sustained pain and after stimulus offset. The posterior cingulate cortex, a
      neural pain signature modulating region, mirrored this late signal reduction in
      autism spectrum disorder. Intact early responses, followed by diminished late
      responses to sustained pain, may reflect altered pain coping or evaluation in
      autism spectrum disorder. Evidence of a dichotomous neural response to initial
      versus protracted pain may clarify the coexistence of both hypo- and
      hyperresponsiveness to pain in autism spectrum disorder.

PMID- 28513187
TI  - Stress and Response to Treatment: Insights From a Pilot Study Using a 4-week
      Contemplative Self-Healing Meditation Intervention for Posttraumatic Stress in
      Breast Cancer.
AB  - Along with symptoms of anxiety and depression, many breast cancer survivors
      experience symptoms of posttraumatic stress disorder (PTSD) that may worsen in
      the setting of other stressful life events. The aim of this pilot study was to
      evaluate whether a 4-week version of our Contemplative Self-Healing program would
      have different effects in reducing PTSD symptoms between breast cancer survivors
      with or without chronic stress at baseline. PTSD symptoms were measured using the
      Impact of Events scale (IES). A linear mixed model analysis was used to evaluate
      within patients changes in IES score. Results showed that breast cancer patients
      who were experiencing chronic stress reported greater improvement in IES score
      than those without chronic stress. Our preliminary findings shed light on the
      need to evaluate life stressors in breast cancer patients. Evaluating chronic
      stress may be essential in predicting which cancer patients may benefit most from
      a psychological intervention.

PMID- 28513188
TI  - Late presentation of esophageal rupture following blunt thoracic trauma.
AB  - Esophageal rupture following blunt thoracic trauma is extremely rare. A 30-year
      old man sustained a road traffic accident causing blunt thoracic trauma that
      resulted in lower esophageal rupture. He presented 24 h after the initial trauma
      and was managed with primary repair and aggressive lavage with a drainage
      procedure. Early identification and repair of esophageal rupture is vital for
      preventing mediastinitis, but an aggressive surgical and postoperative management
      strategy can prevent mortality even in late presentations.

PMID- 28513189
TI  - Transcatheter aortic valve implantation: the transaortic approach.
AB  - Background Transcatheter aortic valve implantation has been established as a safe
      and effective treatment option for patients at high or prohibitive surgical risk.
      However, some patients may not be suitable for the transfemoral approach due to
      severe iliofemoral disease or aneurysmal disease of the thoracoabdominal aorta.
      The aim of this case series was to evaluate the feasibility and clinical outcomes
      of the transaortic approach. Methods From May 2015 to June 2016, 5 patients (mean
      age 78.4 +/- 3.9 years) with severe symptomatic aortic stenosis underwent
      transaortic transcatheter aortic valve implantation after a heart team
      discussion. They were considered to be at high surgical risk and ineligible for
      the transfemoral approach due to iliofemoral or thoracoabdominal aortic disease.
      Results A CoreValve Evolut R was successfully deployed in all 5 patients. We
      performed 4 right mini-parasternal incisions and one J-incision partial
      sternotomy. None of the patients required permanent pacemaker implantation, one
      required reopening of the mini-parasternal incision for postoperative bleeding.
      Follow-up echocardiography one month after the procedure showed improvement in
      the mean aortic gradient (from 63.2 to 8.3 mm Hg) and aortic valve area (from
      0.62 to 2.2 cm2). None of the patients had more than mild paravalvular leakage.
      There was no intraoperative or 30-day mortality. Conclusion Transaortic
      transcatheter aortic valve implantation is a safe and feasible option for
      patients with severe aortic stenosis who are considered unsuitable for
      transfemoral aortic valve implantation.

PMID- 28513190
TI  - Prevalence and correlates of bullying victimisation and perpetration in a
      nationally representative sample of Australian youth.
AB  - OBJECTIVE: Bullying prevalence studies are limited by varied measurement methods
      and a lack of representative samples. This study estimated the national
      prevalence of bullying victimisation, perpetration and combined victim
      perpetration experiences in a representative population-based sample of
      Australian youth. The relationships between the three types of bullying
      involvement with a range of mental health symptoms and diagnoses were also
      examined. METHODS: A randomly selected nationally representative sample aged 11
      17 years ( N = 2967, Mage = 14.6 years; 51.6% male) completed the youth component
      of the Second Australian Child and Adolescent Survey of Mental Health and
      Wellbeing (Young Minds Matter). Parents or carers also completed a structured
      face-to-face interview that asked questions about a single randomly selected
      child in the household. The youth survey comprised self-reported bullying
      victimisation and perpetration (Olweus Bully-Victim Questionnaire-adapted),
      psychological distress (K10), emotional and behavioural problems (Strengths and
      Difficulties Questionnaire), as well as self-harm, suicide attempts and substance
      use. Modules from the Diagnostic Interview Schedule for Children Version IV were
      administered to all youth and parents to assess for mental disorder diagnoses
      (major depressive disorder, any anxiety disorder and any externalising disorder
      [attention-deficit hyperactivity disorder, oppositional defiant disorder and
      conduct disorder]). RESULTS: The 12-month prevalence of bullying victimisation
      was 13.3%, perpetration 1.6% and victim-perpetration 1.9%. Logistic regression
      models showed all forms of involvement in bullying were associated with increased
      risk of psychological distress, emotional and behavioural problems, substance
      use, self-harm and attempted suicide. Victimisation and victim-perpetration were
      associated with youth-reported major depressive disorder. There were also
      significant associations between bullying involvement and parent-reported
      diagnoses of major depressive disorder, any anxiety disorder and any
      externalising disorder. CONCLUSION: Bullying continues to be frequently
      experienced by Australian adolescents. The current findings showed that
      involvement in any bullying behaviour was associated with increased risk of
      concurrent mental health problems. This evidence can be used to inform decisions
      concerning the allocation of resources to address this important health issue.

PMID- 28513191
TI  - The antecedents and outcomes of dyadic coping in close personal relationships: a
      systematic review and narrative synthesis.
AB  - BACKGROUND AND OBJECTIVES: Theories of dyadic coping and empirical literature
      have intermittently and inconsistently highlighted antecedents and outcomes of
      dyadic coping. The purpose of this review was to systematically identify the
      antecedents and outcomes of dyadic coping in close personal relationships.
      DESIGN: A PRISMA-guided systematic review and narrative synthesis. METHODS:
      Literature searches were conducted using CINAHL, PubMed, PsycINFO, and citation
      pearl growing to identify studies that were relevant to the aim of the review.
      The search strategy and exclusion criteria led to a final sample of 46 studies
      that each highlighted antecedents and outcomes of dyadic coping among married
      couples. Each study was critically appraised and analyzed using narrative
      synthesis. RESULTS: The narrative synthesis highlighted five antecedents
      (learning, gender, relationship characteristics, relationship role, and cultural
      influences) and two outcomes (relationship functioning and personal health) of
      dyadic coping. CONCLUSION: The review exposes inconsistencies in the
      conceptualization of dyadic coping, highlights a range of antecedents that
      influence dyadic coping, and suggests that dyadic coping can have positive
      benefits for relationship functioning and personal health. The findings have
      implications for future research and practice (e.g. when working with couples to
      improve relationship functioning).

PMID- 28513192
TI  - The haemodynamic effect of an adjustable band in an arteriovenous fistula.
AB  - A number of treatment approaches exist for excessive flowrate arteriovenous
      fistulae. Banding has a number of advantages, yet there is concern over its use
      due to reported high post-surgery thrombosis rates. A computational study is
      conducted of a new technique, to elucidate the hemodynamics present in the
      process. The key improvement involves the use of an adjustable band which can be
      used to optimise the flowrate during the surgery. The pressure and flowrate
      changes are apparent from the computational results and the computational results
      also demonstrate that further optimization may be possible. We then present a
      small cohort of five cases where the new banding procedure has been implemented
      with success. The new technique was combined with intra-operative ultrasound flow
      monitoring.

PMID- 28513193
TI  - Impact of Health Literacy on Time Spent Seeking Hand Care.
AB  - BACKGROUND: Patients with limited health literacy may have less knowledge and
      fewer resources for efficient access and navigation of the health care system. We
      tested the null hypothesis that there is no correlation between health literacy
      and total time spent seeking hand surgery care. METHODS: New patients visiting a
      hand surgery clinic at a suburban academic medical center were asked to complete
      a questionnaire to determine demographics, total time spent seeking hand surgery
      care, and outcomes. A total of 112 patients were included in this study. RESULTS:
      We found health literacy levels did not correlate with total time seeking hand
      surgery care or from booking an appointment to being evaluated in clinic.
      CONCLUSIONS: In this suburban academic medical center, patients with low health
      literacy do not spend more time seeking hand surgery care and do have longer
      delays between seeking and receiving care. The finding that-at least in this
      setting-health literacy does not impact patient time seeking hand care suggests
      that resources to improve health disparities can be focused elsewhere in the care
      continuum.

PMID- 28513195
TI  - Binge drinking: Health impact, prevalence, correlates and interventions.
AB  - OBJECTIVE: Binge drinking (also called heavy episodic drinking, risky single
      occasion drinking etc.) is a major public health problem. This paper provides an
      overview of recently published evidence concerning the definition and
      measurement, prevalence rates, health impact, demographic and psychosocial
      correlates of, and interventions for, binge drinking. DESIGN: Narrative review.
      RESULTS: Mostly occurring among young people at weekends, binge drinking
      increases the risk of both acute (e.g. injuries) and long-term negative
      consequences (e.g. alcohol disorders). Binge drinkers tend to be extrovert,
      impulsive and sensation-seeking. Stress, anxiety, traumatic events and depression
      are also related to binge drinking. Both alcohol-related behaviour of parents and
      general parenting (e.g. parenting styles, monitoring) are also important. Other
      major risk factors for binge drinking are frequently spending time with friends
      who drink, and the drinking norms observed in the wider social environment (e.g.
      school, community, culture). Emergency departments, birthday parties,
      fraternities and the workplace serve as settings for interventions; these are
      increasingly delivered via digital and mobile technology. There is evidence of
      small-sized effects across approaches (brief interventions, personalised
      normative feedback, protective behavioural strategies etc.) and populations.
      CONCLUSION: A more consistent terminology, investigating multi-level influences
      and identifying the most effective intervention components are challenges for
      future research.

PMID- 28513194
TI  - Long noncoding RNAs: emerging regulators of tumor angiogenesis.
AB  - Long noncoding RNAs (lncRNAs) participate in multiple biological processes
      especially human diseases, of which, tumor seems to be one of the most
      significant. Angiogenesis has been deemed to have a pivotal role in a series of
      tumor biological behaviors in tumorigenesis, progression and prognosis. Emerging
      evidences suggested that lncRNAs are involved in tumor angiogenesis and lncRNAs
      have already been verified to be potential biomarkers and promising therapeutic
      targets. This review summarized emerging angiogenesis-related lncRNAs, discussed
      their mechanisms interacting with cytokines, cancer stem cells, miRNAs and tumor
      hypoxia microenvironment, and demonstrated if lncRNAs could be new candidate
      targets of antiangiogenesis therapy.

PMID- 28513196
TI  - Synthesis and in vivo antimalarial activity of novel naphthoquine derivatives
      with linear/cyclic structured pendants.
AB  - AIM: Naphthoquine (NQ) was discovered by our institute as an antimalarial
      candidate in 1980s, and currently employed as an artemisinin-based combination
      therapy partner drug. Resistance to NQ was found in mouse model in laboratory,
      and might emerge in future as widely used. METHODOLOGY: We herein report the
      design and synthesis of NQ derivatives by replacing t-butyl moiety with
      linear/cyclic structured pendants. All the target compounds 6a-l and
      intermediates 5a-h were tested for their in vivo antimalarial activity against
      Plasmodium berghei K173 strain in mice. RESULTS: Compounds 6a and 6j were found
      to have a comparable or slightly more potent activity (the 50% effective dose
      [ED50], which is required to decrease parasitemia by 50%: 0.38-0.43 mg/kg) than
      NQ (ED50: 0.48 mg/kg). CONCLUSION: The newly designed compounds 6a and 6j might
      be promising antimalarial candidates for further research.

PMID- 28513197
TI  - Uptake of telehealth implementation for COPD patients in a high-poverty, inner
      city environment: A survey.
AB  - This study aimed to investigate computer and internet access and education
      attained in patients with chronic obstructive pulmonary disease (COPD) as
      potential barriers to implementation of telemedicine. We prospectively assessed
      98 patients admitted with an acute exacerbation of COPD (mean age: 70.5 +/- 9.3
      years; force expired volume in the first second: 0.75 +/- 0.39 L; 59% male)
      recording educational level attained and home computer and internet access.
      Hospital readmission surveillance occurred up to 2.7 (2.6-2.8) years following
      the index hospital admission. Only 16% of patients had a computer and only 14%
      had internet access; this group were younger and more educated than those without
      a computer. There was no difference in hospital readmissions over 2 years between
      those with and without access to a computer or internet. Only 12% of the whole
      cohort were educated to a school leaving age of 16 years and this group were more
      likely to be still working. School leaving age was directly associated with fewer
      hospital readmissions ( r = 0.251, p = 0.031). In conclusion, these data
      highlight the current challenges to the widespread implementation of telehealth
      in COPD patients as there is limited availability of computer and internet access
      with such patients demonstrating a lower level of education achievement.

PMID- 28513199
TI  - Experience of exclusion: A framework analysis of socioeconomic factors affecting
      cardiac rehabilitation participation among patients with acute coronary syndrome.
AB  - BACKGROUND: The Danish public healthcare system provides comprehensive care based
      on the principle of equal access. However, it is well documented that patients
      with low socioeconomic position are less likely to participate in cardiac
      rehabilitation. More knowledge is needed to understand this phenomenon. The aim
      of the study was to explore the patient experience of barriers to completion of
      phase II cardiac rehabilitation, and to investigate the impact of socioeconomic
      factors on completion of cardiac rehabilitation. METHODS: The study had a
      qualitative explorative design using semi-structured individual or dyadic
      interviews with patients ( n = 24) and close relatives ( n = 12). Informants were
      sampled from a quantitative prospective study of 302 patients with acute coronary
      syndrome and data were analyzed using the framework method. RESULTS: Patients in
      different socioeconomic groups were challenged by a rigid and non-individualized
      rehabilitation program. A total of five themes were identified that might explain
      non-participation in cardiac rehabilitation: exclusion by time and place,
      exclusion by health beliefs, exclusion from counseling, exclusion by alienation,
      and exclusion of relatives. The themes were described in a matrix of
      socioeconomic factors of age, sex, education and employment. CONCLUSIONS:
      Patients in various socioeconomic subgroups felt excluded from cardiac
      rehabilitation for different reasons. This study supports earlier findings and
      provides examples of real-life issues that need to be addressed to prevent
      attrition and encourage participation. Equal access to cardiac rehabilitation can
      only be reached if the physical and psychological needs of patient and family are
      met by tailoring therapy to consider age, sex, education and employment groups.

PMID- 28513198
TI  - Cleaning and infection control of airway clearance devices used by CF patients.
AB  - Respiratory treatment for cystic fibrosis (CF) patients includes use of
      respiratory devices. Contamination of airway clearance devices has not been
      adequately explored. We aimed to determine whether airway clearance devices are
      contaminated after use and whether cleaning guidelines for nebulizers are as
      effective for airway clearance devices. Patients brought their airway clearance
      devices to the clinic. Swabs from the devices were taken before and after
      cleaning and were cultured for bacterial counts. Total colony-forming units (CFU)
      was determined, and predominant colonies were identified using Matrix-Assisted
      Laser Desorption Ionization Time-of-Flight Mass Spectrometry technology. Thirty
      devices were collected from 23 patients. Most of the devices (28/30) were
      contaminated when brought to the clinic. Complete bacterial eradication was
      achieved in 15 (50%) samples and partial eradication in 9 (30%). The cleaning was
      totally ineffective in four samples. Median CFU decreased significantly from 1250
      (IQR 25-75% 175-10.000) to 0 (IQR 25-75% 0-700) before and after cleaning ( p <
      0.0001). The predominant organisms were identified in five samples only, and
      there was no concordance with sputum culture results. Airway clearance devices
      are contaminated after use, and appropriate cleaning can reduce contamination.
      The effect on disease progression in CF patients is unclear. There is a need for
      infection prevention and control guidelines for the growing number of respiratory
      devices.

PMID- 28513201
TI  - Real-World Evolution of Robot Morphologies: A Proof of Concept.
AB  - Evolutionary robotics using real hardware has been almost exclusively restricted
      to evolving robot controllers, but the technology for evolvable morphologies is
      advancing quickly. We discuss a proof-of-concept study to demonstrate real robots
      that can reproduce. Following a general system plan, we implement a robotic
      habitat that contains all system components in the simplest possible form. We
      create an initial population of two robots and run a complete life cycle,
      resulting in a new robot, parented by the first two. Even though the individual
      steps are simplified to the maximum, the whole system validates the underlying
      concepts and provides a generic workflow for the creation of more complex
      incarnations. This hands-on experience provides insights and helps us elaborate
      on interesting research directions for future development.

PMID- 28513202
TI  - Abstraction, Sensory-Motor Coordination, and the Reality Gap in Evolutionary
      Robotics.
AB  - One of the major challenges of evolutionary robotics is to transfer robot
      controllers evolved in simulation to robots in the real world. In this article,
      we investigate abstraction of the sensory inputs and motor actions as a tool to
      tackle this problem. Abstraction in robots is simply the use of preprocessed
      sensory inputs and low-level closed-loop control systems that execute higher
      level motor commands. To demonstrate the impact abstraction could have, we
      evolved two controllers with different levels of abstraction to solve a task of
      forming an asymmetric triangle with a homogeneous swarm of micro air vehicles.
      The results show that although both controllers can effectively complete the task
      in simulation, the controller with the lower level of abstraction is not
      effective on the real vehicle, due to the reality gap. The controller with the
      higher level of abstraction is, however, effective both in simulation and in
      reality, suggesting that abstraction can be a useful tool in making evolved
      behavior robust to the reality gap. Additionally, abstraction aided in reducing
      the computational complexity of the simulation environment, speeding up the
      optimization process. Preeminently, we show that the optimized behavior exploits
      the environment (in this case the identical behavior of the other robots) and
      performs input shaping to allow the vehicles to fly into and maintain the
      required formation, demonstrating clear sensory-motor coordination. This shows
      that the power of the genetic optimization to find complex correlations is not
      necessarily lost through abstraction as some have suggested.

PMID- 28513200
TI  - HIV-infected individuals who use alcohol and other drugs, and virologic
      suppression.
AB  - People living with HIV (PLWH) on antiretroviral therapy (ART) who use substances
      were examined to (a) describe those with virologic control and (b) determine
      which substance use-factors are associated with lack of virologic control.
      Participants were adult PLWH taking ART with either past 12-month DSM-IV
      substance dependence or past 30-day alcohol or illicit drug use. Substance use
      factors included number of DSM-IV alcohol or drug dependence criteria and past 30
      day specific substance use. Associations with HIV viral load (HVL) (<200 vs.
      >=200 copies/mL) were tested using logistic regression models. Multivariable
      analyses adjusted for age, sex, homelessness and anxiety or depression.
      Participants (n = 202) were median age 50 years, 66% male, 51% African American
      and 75% self-reported >=90% past 30-day ART adherence. Though HVL suppression
      (HVL <200 copies/mL) was achieved in 78% (158/202), past 30-day substance use was
      common among this group: 77% cigarette use; 51% heavy alcohol use; 50% marijuana;
      27% cocaine; 16% heroin; and 15% illicit prescription opioid use. After adjusting
      for covariates, specific substance use was not associated with a detectable HVL,
      however number of past 12-month DSM-IV drug dependence criteria was (adjusted
      odds ratio = 1.23 for each additional criterion, 95% CI: 1.04-1.46). Three
      quarters of a substance-using cohort of PLWH receiving ART had virologic control
      and >=90% ART adherence. Substance dependence criteria (particularly drug
      dependence), not specifically substance use, were associated with lack of
      virologic control. Optimal HIV outcomes can be achieved by individuals who use
      alcohol or drugs and addressing symptoms of substance dependence may improve HIV
      related outcomes.

PMID- 28513203
TI  - Automating the Incremental Evolution of Controllers for Physical Robots.
AB  - Evolutionary robotics is challenged with some key problems that must be solved,
      or at least mitigated extensively, before it can fulfill some of its promises to
      deliver highly autonomous and adaptive robots. The reality gap and the ability to
      transfer phenotypes from simulation to reality constitute one such problem.
      Another lies in the embodiment of the evolutionary processes, which links to the
      first, but focuses on how evolution can act on real agents and occur
      independently from simulation, that is, going from being, as Eiben, Kernbach, &
      Haasdijk [2012, p. 261] put it, "the evolution of things, rather than just the
      evolution of digital objects...." The work presented here investigates how fully
      autonomous evolution of robot controllers can be realized in hardware, using an
      industrial robot and a marker-based computer vision system. In particular, this
      article presents an approach to automate the reconfiguration of the test
      environment and shows that it is possible, for the first time, to incrementally
      evolve a neural robot controller for different obstacle avoidance tasks with no
      human intervention. Importantly, the system offers a high level of robustness and
      precision that could potentially open up the range of problems amenable to
      embodied evolution.

PMID- 28513204
TI  - On Design Mining: Coevolution and Surrogate Models.
AB  - Design mining is the use of computational intelligence techniques to iteratively
      search and model the attribute space of physical objects evaluated directly
      through rapid prototyping to meet given objectives. It enables the exploitation
      of novel materials and processes without formal models or complex simulation. In
      this article, we focus upon the coevolutionary nature of the design process when
      it is decomposed into concurrent sub-design-threads due to the overall complexity
      of the task. Using an abstract, tunable model of coevolution, we consider
      strategies to sample subthread designs for whole-system testing and how best to
      construct and use surrogate models within the coevolutionary scenario. Drawing on
      our findings, we then describe the effective design of an array of six
      heterogeneous vertical-axis wind turbines.

PMID- 28513205
TI  - Introduction to the Evolution of Physical Systems Special Issue.

PMID- 28513206
TI  - A General Architecture for Robotics Systems: A Perception-Based Approach to
      Artificial Life.
AB  - Departing from the conventional view of the reasons for the behavior of living
      systems, this research presents a radical and unique view of that behavior, as
      the observed side effects of a hierarchical set of simple, continuous, and
      dynamic negative feedback control systems, by way of an experimental model
      implemented on a real-world autonomous robotic rover. Rather than generating
      specific output from input, the systems control their perceptual inputs by
      varying output. The variables controlled do not exist in the environment, but are
      entirely internal perceptions constructed as a result of the layout and
      connections of the neural architecture. As the underlying processes are
      independent of the domain, the architecture is universal and thus has significant
      implications not only for understanding natural living systems, but also for the
      development of robotics systems. The central process of perceptual control has
      the potential to unify the behavioral sciences and is proposed as the missing
      behavioral principle of Artificial Life.

PMID- 28513207
TI  - Evolutionary Developmental Robotics: Improving Morphology and Control of Physical
      Robots.
AB  - Evolutionary algorithms have previously been applied to the design of morphology
      and control of robots. The design space for such tasks can be very complex, which
      can prevent evolution from efficiently discovering fit solutions. In this article
      we introduce an evolutionary-developmental (evo-devo) experiment with real-world
      robots. It allows robots to grow their leg size to simulate ontogenetic
      morphological changes, and this is the first time that such an experiment has
      been performed in the physical world. To test diverse robot morphologies, robot
      legs of variable shapes were generated during the evolutionary process and
      autonomously built using additive fabrication. We present two cases with evo-devo
      experiments and one with evolution, and we hypothesize that the addition of a
      developmental stage can be used within robotics to improve performance. Moreover,
      our results show that a nonlinear system-environment interaction exists, which
      explains the nontrivial locomotion patterns observed. In the future, robots will
      be present in our daily lives, and this work introduces for the first time
      physical robots that evolve and grow while interacting with the environment.

PMID- 28513208
TI  - Self-Organization of Vocabularies under Different Interaction Orders.
AB  - Traditionally, the formation of vocabularies has been studied by agent-based
      models (primarily, the naming game) in which random pairs of agents negotiate
      word-meaning associations at each discrete time step. This article proposes a
      first approximation to a novel question: To what extent is the negotiation of
      word-meaning associations influenced by the order in which agents interact?
      Automata networks provide the adequate mathematical framework to explore this
      question. Computer simulations suggest that on two-dimensional lattices the
      typical features of the formation of word-meaning associations are recovered
      under random schemes that update small fractions of the population at the same
      time; by contrast, if larger subsets of the population are updated, a periodic
      behavior may appear.

PMID- 28513210
TI  - Alzheimer Europe's position on involving people with dementia in research through
      PPI (patient and public involvement).
AB  - This paper reflects Alzheimer Europe's position on PPI (patient and public
      involvement) in the context of dementia research and highlights some of the
      challenges and potential risks and benefits associated with such meaningful
      involvement. The paper was drafted by Alzheimer Europe in collaboration with
      members of INTERDEM and the European Working Group of People with Dementia. It
      has been formally adopted by the Board of Alzheimer Europe and endorsed by the
      Board of INTERDEM and by the JPND working group 'Dementia Outcome Measures -
      Charting New Territory'. Alzheimer Europe is keen to promote the involvement of
      people with dementia in research, not only as participants but also in the
      context of PPI, by generating ideas for research, advising researchers, being
      involved in consultations and being directly involved in research activities.
      This position paper is in keeping with this objective. Topics covered include,
      amongst others, planning involvement, establishing roles and responsibilities,
      training and support, managing information and input from PPI, recognising the
      contribution of people with dementia involved in research in this way, promoting
      and protecting the rights and well-being of people with dementia, training and
      support, and promoting an inclusive approach and the necessary infrastructure for
      PPI in dementia research.

PMID- 28513209
TI  - Caregiver determinants of patient clinical event risk in heart failure.
AB  - BACKGROUND: Preventing hospitalization and improving event-free survival are
      primary goals of heart failure (HF) treatment according to current European
      Society of Cardiology guidelines; however, substantial uncertainty remains in our
      ability to predict risk and improve outcomes. Although caregivers often assist
      patients to manage their HF, little is known about their influence on clinical
      outcomes. AIMS: To quantify the influence of patient and caregiver
      characteristics on patient clinical event risk in HF. METHODS: This was a
      secondary analysis of data using a sample of Italian adults with HF and their
      informal caregivers ( n = 183 patient-caregiver dyads). HF patients were followed
      over 12 months for the following clinical events: hospitalization for HF,
      emergency room visit for HF or all-cause mortality. Influence of baseline
      caregiver- and patient-level factors (patient and caregiver age; dyad
      relationship type; patient New York Heart Association (NYHA) Class, cognition,
      and comorbidities; and caregiver strain, mental health status, and contributions
      to HF self-care) on patient risk of death or hospitalization/emergency room use
      was quantified using Cox proportional hazards regression. RESULTS: Over the
      course of follow up, 32.8% of patients died, 19.7% were hospitalized for HF and
      10.4% visited the emergency room. Higher caregiver strain, better caregiver
      mental health status and greater caregiver contributions to HF self-care
      maintenance were associated with significantly better event-free survival. Worse
      patient functional class and greater caregiver contributions to patient self-care
      management were associated with significantly worse patient event-free survival.
      CONCLUSION: Considering caregiving factors together with patient factors
      significantly increases our understanding of patient clinical event risk in HF.

PMID- 28513211
TI  - Image quality of low-radiation dose left atrial CT using filtered back projection
      and an iterative reconstruction algorithm: intra-individual comparison in
      unselected patients undergoing pulmonary vein isolation.
AB  - Background Computed tomography (CT) of the left atrium (LA) is performed prior to
      pulmonary vein isolation (PVI) to improve success of circumferential ablation for
      atrial fibrillation. The ablation procedure itself exposes patients to
      substantial radiation doses, therefore radiation dose reduction in pre-ablational
      imaging is of concern. Purpose To assess and compare diagnostic performance of
      low-radiation dose preprocedural CT in patients scheduled for PVI using two types
      of reconstruction algorithms. Material and Methods Forty-six patients (61 +/- 10
      years) scheduled for PVI were enrolled in this study irrespective of body-mass
      index or cardiac rhythm at examination. An electrocardiographically triggered
      dual-source CT scan was performed. Filtered back projection (FBP) and iterative
      reconstruction (IR) algorithms were applied. Images were integrated into an
      electroanatomic mapping (EAM) system. Subjective image quality was scored
      independently by two readers on a five-point scale for both reconstruction
      algorithms (1 = excellent to 5 = non-diagnostic). Signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR), and effective radiation dose were calculated.
      Results Data acquisition and EAM integration were successful in all patients.
      Median image quality score was 1 for both FBP (quartiles = 1, 1.62; range = 1-3)
      and IR (quartiles = 1, 1.5; range = 1-3). Mean SNR was 7.61 +/- 2.14 for FBP and
      9.02 +/- 2.69 for IR. Mean CNR was 5.92 +/- 1.80 for FBP and 6.95 +/- 2.29 for
      IR. Mean effective radiation dose was 0.3 +/- 0.1 mSv. Conclusion At a radiation
      dose of 0.3 +/- 0.1 mSv, high-pitch dual-source CT yields LA images of
      consistently high quality using both FBP and IR. IR raises SNR and CNR without
      significantly improving subjective image quality.

PMID- 28513213
TI  - Remote Ischemic Conditioning: The Commercial Market? CellAegis Perspective.
AB  - Remote ischemic conditioning (RIC) is at a pivotal point in its evolution, both
      in terms of its adoption as a therapy and its viability commercially. The most
      usual way of inducing RIC, with a standard blood pressure cuff and a stopwatch,
      is time-consuming and potentially inaccurate and unsafe. Development of automated
      devices have facilitated large-scale randomized trials and will make clinical
      deployment of the technique more straightforward. Both the medical and commercial
      future of RIC will depend on the results of upcoming phase 3 pivotal trials.

PMID- 28513212
TI  - An Optical-Fiber-Based Smart Textile (Smart Socks) to Manage Biomechanical Risk
      Factors Associated With Diabetic Foot Amputation.
AB  - OBJECTIVE: This study aimed to validate a smart-textile based on fiber-optics for
      simultaneous measurement of plantar temperature, pressure, and joint angles in
      patients with diabetic peripheral neuropathy (DPN). METHODS: After in-vitro
      validation in the laboratory, 33 eligible subjects with DPN were recruited (age:
      58 +/- 8 years, BMI: 31.5 +/- 8 kg/m2) for assessing plantar pressure and
      temperature during habitual gait-speed in a clinical-setting. All participants
      were asked to walk at their habitual speed while wearing a pair of sensorized
      socks made from highly flexible fiber optics (SmartSox). An algorithm was
      designed to estimate temperature, pressure, and toe range of motion from optical
      wavelength generated from SmartSox. To validate the device, results from thermal
      stress response (TSR) using thermography and peak pressure measured by
      computerized pressure insoles (F-Scan) were used as gold standards. RESULTS: In
      laboratory and under controlled conditions, the agreements for parameters of
      interest were excellent ( r > .98, P = .000), and no noticeable cross-talks
      between measurements of temperature, angle, and pressure were observed. During
      clinical data acquisition, a significant correlation was found for pressure
      profile under different anatomical regions of interest between SmartSox and F
      Scan ( r = .67, P < .050) as well as between thermography and SmartSox ( r = .55,
      P < .050). CONCLUSION: This study demonstrates the validity of an innovative
      smart textile for assessing simultaneously the key parameters associated with
      risk of foot ulcers in patients with DPN. It may empower clinicians to
      objectively stratify foot risk and provide timely care. Another study is
      warranted to validate its clinical application in preventing limb threating
      problems in patients with DPN.

PMID- 28513214
TI  - The Future of Remote Ischemic Conditioning.

PMID- 28513215
TI  - Presence of Air Trapping and Mosaic Attenuation on Chest Computed Tomography
      Predicts Survival in Chronic Hypersensitivity Pneumonitis.
AB  - RATIONALE: Significant heterogeneity of computed tomography (CT) presentation
      exists within chronic hypersensitivity pneumonitis (HP). There are limited data
      aimed at delineating the prognostic value of specific CT features, distribution,
      and patterns in chronic HP. OBJECTIVES: To examine whether the presence of CT
      mosaic attenuation (MA) and air trapping (AT), and the distribution or patterns
      of fibrosis impact survival in subjects with chronic HP. METHODS: We
      retrospectively identified 110 consecutively enrolled, well-characterized, biopsy
      proven adult subjects with chronic HP between 1982 and 2015 from the National
      Jewish Health interstitial lung disease research database. The first available CT
      scan of diagnostic quality from each subject was formally evaluated for specific
      CT findings associated with chronic HP and for overall CT pattern. A Cox
      proportional hazards model was used to identify independent predictors in time-to
      death analysis, and bootstrap analysis was performed for internal model
      validation. RESULTS: Fibrotic HP (65%; 72/110) was most often peripheral in the
      axial plane and lower lung preponderant. The distribution of lung disease in
      those without fibrosis was most often axially and zonally diffuse. There was no
      association between survival and CT distribution or CT pattern in the whole
      cohort or within the fibrotic subset of subjects. After multivariate adjustment,
      AT/MA was independently associated with survival in the whole cohort (HR = 0.26;
      95% confidence interval = 0.07-0.97). Results were similar after restricting the
      analyses to fibrotic HP cases. CONCLUSIONS: Among subjects with chronic HP, the
      presence of CT AT/MA may identify subjects with better prognosis.

PMID- 28513216
TI  - Efficacy of Syringe Filtration for the Selective Isolation of Campylobacter from
      Chicken Carcass Rinse.
AB  - We investigated the efficacy of syringe filtration for selective isolation of
      Campylobacter from chicken carcass rinse by combining syringe filtration with the
      conventional culture method. Whole chicken carcass rinses were incubated in
      Bolton enrichment broth, set aside or subjected to syringe filtration, and
      streaked on Campy-Cefex agar with or without cefoperazone antibiotic supplement.
      Compared with the conventional method without filtration, 0.65-MUm-pore-size
      syringe filtration resulted in a significantly higher number of Campylobacter
      positive samples (23.8 to 37.5% versus 70.0 to 72.5%; P < 0.05), a lower number
      of plates contaminated with non-Campylobacter (93.8% versus 6.3 to 26.3%), and a
      lower growth index (1 = growth of a few colonies; 2 = growth of colonies on about
      half of the plate; and 3 = growth on most of the plate) for competing microbiota
      (2.9 to 3.0 versus 1.2 to 1.4). When syringe filtration was applied, agar plates
      containing the antibiotic had significantly less contamination (6.3% versus
      26.3%; P < 0.05) and a lower growth index (1.2 versus 1.4) compared with plates
      without the antibiotic, although the Campylobacter isolation rate was similar (P
      > 0.05). Syringe filtration combined with conventional enrichment improved the
      rate and selectivity of Campylobacter isolation from chicken carcasses.

PMID- 28513217
TI  - A Preliminary Study on the Effect of Computer-Aided Designed and Manufactured
      Orthoses on Chronic Plantar Heel Pain.
AB  - INTRODUCTION: Chronic plantar heel pain (CPHP) is a significant, painful
      condition referring to a range of undifferentiated foot conditions that affect
      the heel of the foot. METHOD: Participants presenting with CPHP of more than 6
      months' duration were recruited on a first through the door basis. Computer-Aided
      Design and Computer-Aided Manufactured (CAD-CAM) orthoses were designed and
      constructed for each participant, then dispensed as per normal practice. Pre- and
      postintervention assessment of pain was performed at baseline and after 6 weeks
      of use, utilizing the pain subset of the Foot Function Index (FFI). RESULTS:
      There was a significant reduction in the mean pain scores for all participants in
      all constructs of the FFI. Total FFI score was also significant ( P = .003).
      CONCLUSION: CAD-CAM orthoses have the potential to become a treatment modality of
      choice in CPHP since they have resulted in a significant improvement in heel pain
      after only 6 weeks' use. LEVELS OF EVIDENCE: Therapeutic, Level IV: Prospective,
      comparative trial.

PMID- 28513218
TI  - Three Cycles of Radiofrequency Ablation Are More Efficacious Than Two in the
      Management of Morton's Neuroma.
AB  - BACKGROUND: Morton's neuroma is a common cause of forefoot pain. Outcomes of
      conservative therapy are mixed and many patients undergo operative intervention.
      Radiofrequency ablation has recently gained favor as a treatment option, although
      the optimal regime is unknown. This study investigates the effectiveness of 2
      versus 3 cycles of radiofrequency ablation for the treatment of Morton's neuroma.
      METHODS: We surveyed a cohort of patients with Morton's neuroma who had
      progressed to radiofrequency ablation after failed conservative treatment.
      Patients received either 2 or 3 cycles of radiofrequency ablation by a single
      surgeon. We assessed patients based on their change in numerical pain rating
      scale, symptom improvement, complications, and progression to surgical excision
      through a series of telephone interviews. Outcomes between the 2 treatment arms
      were compared by parametric tests. RESULTS: Twenty-eight patients were included
      in the study. Eighteen patients with 21 neuromas received 2 cycles and 10
      patients with 11 neuromas received 3 cycles. Mean time of follow-up was 12.9
      months. Overall, 88% of patients were either very or moderately satisfied with
      their outcome. In patients who received 2 cycles mean numerical pain scores
      decreased from 7.9 +/- 1.1 to 3.4 +/- 2.4 postprocedure. Three patients
      progressed to operative excision. In patients who received 3 cycles, numerical
      pain scores decreased from 8.0 +/- 1.0 to 1.5 +/- 2.0 postprocedure. One patient
      progressed to operative excision. Patients who received 3 cycles had reduced
      medium-term pain postoperatively compared with 2 cycles (3.4 +/- 2.4 vs 1.5 +/-
      2.0, P = .011). CONCLUSION: Radiofrequency ablation provides a high rate of
      patient satisfaction in the treatment of Morton's neuroma with few side effects.
      It appears that 3 cycles may be superior to 2 cycles but a randomized controlled
      trial will be required to confirm these results. LEVELS OF EVIDENCE:
      Intervention, Level III: Comparative study without concurrent controls.

PMID- 28513219
TI  - A temporofrontal fascia flap that penetrated temporal muscle for the
      reconstruction of an anterior skull base bone and dura: a technical case report.
AB  - During skull base surgery, reconstruction of the dura is a very important
      procedure. Here, the use of a temporofrontal pedicled fascia flap tunnelled
      between temporal muscle fibres is described. This technique is easily performed
      and has a low postoperative morbidity, including skin and temporal muscle
      complications.

PMID- 28513220
TI  - Corrigendum.

PMID- 28513221
TI  - Sericins of mulberry and non-mulberry silkworms for eco-friendly synthesis of
      silver nanoparticles.
AB  - Green synthesis of silver nanoparticles (AgNPs) has received many interests as a
      simple, cost-effective, and environmentally friendly method. This study reported
      the use of sericins extracted from non-mulberry (Samia cynthia ricini) and
      mulberry (Bombyx mori) silkworms for green syntheses of AgNPs. Both sericins
      possessed the reducing activity, which the reducing activity of S. c. ricini
      sericin was significantly higher than that of B. mori sericin. The formation of
      AgNPs facilitated by S. c. ricini sericin was greater than B. mori sericin as
      determined by the intensity of the surfacing plasmon resonance peak of silver at
      412 nm. The synthesized AgNPs using both sericins were spherical and uniform in
      size with the average diameter of ~13 nm. The silver component and the
      crystalline structure was determined by energy-dispersive X-ray and X-ray
      diffraction analyses. The synthesized AgNPs exhibited the antibacterial activity
      against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia
      coli, suggesting their potential application as an effective antibacterial agent.

PMID- 28513222
TI  - The contribution of CYP2C gene subfamily involved in epoxygenase pathway of
      arachidonic acids metabolism to hypertension susceptibility in Russian
      population.
AB  - Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase
      pathway of arachidonic acids metabolism for the pathogenesis of essential
      hypertension (EH). The present study was designed to investigate whether common
      single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8
      (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are
      associated with susceptibility to EH in Russian population. A total of 816
      unrelated Russian individuals comprising 425 EH patients and 391 normotensive
      controls were included into the study. Genotyping of SNPs was performed using the
      MassARRAY 4 system. SNP rs7909236 of CYP2C8 was significantly associated with
      increased risk of EH (OR adjusted for sex and age was 2.99 95% CI 1.39-6.44, P =
      0.005). SNPs rs1934953 CYP2C8 and rs4244285 of CYP2C19 showed association with EH
      risk but at a borderline statistical significance (P <= 0.04). Combination of
      genotypes CYP2C8 rs7909236 TT and CYP2C19 rs4244285 GG was associated with
      increased EH risk (OR 3.34 95%CI 1.48-7.51, P = 0.004). Genotype-phenotype
      correlation analysis showed that the levels of CYP2C8 mRNA were significantly
      correlated with SNP rs7909236 (P = 0.01). in silico functional prediction
      analysis revealed the functionality of majority of investigated SNPs. Thus, genes
      of CYP2C subfamily are important genetic determinants of susceptibility to
      essential hypertension in Russians.

PMID- 28513224
TI  - Letter to the Editor.

PMID- 28513223
TI  - Activation of thromboxane A2 receptors mediates endothelial dysfunction in
      diabetic mice.
AB  - BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease.
      Improvement of endothelial dysfunction in diabetes reduces vascular
      complications. However, the underlying mechanism needs to be uncovered. This
      study was conducted to elucidate whether and how thromboxane A2 receptor (TPr)
      activation contributes to endothelial dysfunction in diabetes. METHODS AND
      RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either
      TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics,
      significantly reduced phosphorylations of endothelial nitric oxide synthase
      (eNOS) at Ser1177 and Akt at Ser473. These effects were abolished by
      pharmacological or genetic inhibitors of TPr. TPr-induced suppression of eNOS and
      Akt phosphorylation was accompanied by upregulation of PTEN (phosphatase and
      tension homolog deleted on chromosome 10) and Ser380/Thr382/383 PTEN
      phosphorylation. PTEN-specific siRNA restored Akt-eNOS signaling in the face of
      TPr activation. The small GTPase, Rho, was also activated by TPr stimulation, and
      pretreatment of HUVECs with Y27632, a Rho-associated kinase (ROCK) inhibitor,
      rescued TPr-impaired Akt-eNOS signaling. In mice, streptozotocin-induced diabetes
      was associated with aortic PTEN upregulation, PTEN-Ser380/Thr382/383
      phosphorylation, and dephosphorylation of Akt (at Ser473) and eNOS (at Ser1177).
      Importantly, administration of TPr antagonist blocked these changes. CONCLUSION:
      We conclude that TPr activation impairs endothelial function by selectively
      inactivating the ROCK-PTEN-Akt-eNOS pathway in diabetic mice.

PMID- 28513225
TI  - Use of the augmentation index from applanation tonometry of the radial artery for
      assessing the extent of coronary artery calcium as assessed by coronary computed
      tomography.
AB  - BACKGROUND: The augmentation index (AI) obtained from applanation tonometry of
      the radial artery is technically the easiest and quickest of available methods
      for assessing arterial stiffness. We tested the hypothesis that the radial AI is
      associated with the extent of coronary artery calcium (CAC) as assessed by
      coronary computed tomography (CCT). METHODS AND RESULTS: This study included 161
      patients with known or suspected coronary artery disease undergoing central
      hemodynamic measurements and CCT. Radial AI was recorded and was corrected in
      accordance with heart rate (radial AI@75). Thirty-seven patients had no CAC (CAC
      score = 0), 85 had low-grade CAC (CAC score = 1-399), and 39 had high-grade CAC
      (CAC score >=400). Coronary risk factors, except for age and serum creatinine,
      were similar among the three groups. There were significant differences in
      brachial systolic blood pressure (SBP) (p = 0.011) and radial AI@75 (%) (p =
      0.006). Multivariate analysis showed that age (beta = 0.27, p = 0.001), serum
      creatinine (beta = 0.18, p = 0.03), and radial AI@75 (beta = 0.24, p = 0.005)
      were significantly associated with ln (CAC score + 1), whereas brachial SBP was
      not. Additionally, serum creatinine (odds ratio: 11.91, 95% confidence interval:
      1.46-112.0, p = 0.02) and radial AI@75 (per 10%) (odds ratio: 1.76, 95%
      confidence interval: 1.22-2.64, p = 0.002) were independent factors associated
      with high-grade CAC. CONCLUSIONS: Our results suggest that the radial AI is
      better for estimating CAC than brachial SBP in patients with known or suspected
      coronary artery disease.

PMID- 28513226
TI  - Application of proteomics to the study of Helicobacter pylori and implications
      for the clinic.
AB  - INTRODUCTION: Helicobacter pylori (H. pylori) is a gram-negative bacterium that
      colonizes the gastric epithelium and mucous layer of more than half the world's
      population. H. pylori is a primary human pathogen, responsible for the
      development of chronic gastritis, peptic ulceration and gastric cancer.
      Proteomics is impacting several aspects of medical research: understanding the
      molecular basis of infection and disease manifestation, identification of
      therapeutic targets and discovery of clinically relevant biomarkers. Areas
      covered: The main aim of the present review is to provide a comprehensive
      overview of the contribution of proteomics to the study of H. pylori infection
      pathophysiology. In particular, we focused on the role of the bacterium and its
      most important virulence factor, CagA, in the progression of gastric cells
      transformation and cancer progression. We also discussed the proteomic approaches
      aimed at the investigation of the host response to bacterial infection. Expert
      commentary: In the field of proteomics of H. pylori, comprehensive analysis of
      clinically relevant proteins (functional proteomics) rather than entire proteomes
      will result in important medical outcomes. Finally, we provided an outlook on the
      potential development of proteomics in H. pylori research.

PMID- 28513227
TI  - Temporal Relationship of Sex Risk Behaviors and Substance Use Severity Among Men
      in Substance Use Treatment.
AB  - Sex risk behaviors and substance use are intertwined. Many men continue to engage
      in high-risk sexual behaviors even when enrolled in substance use disorder (SUD)
      treatment. We hypothesized that changes in sex risk behaviors would coincide with
      changes in drug/alcohol use severity among men in SUD treatment. During an HIV
      risk-reduction trial, men in methadone maintenance and outpatient drug-free
      treatment (N = 359) completed assessments at baseline and six months after. We
      assessed changes in sex risk and substance use severity, using the Addiction
      Severity Index-Lite (ASI-Lite), controlling for treatment condition. In
      multinomial logistic regressions, decreased alcohol severity was significantly
      associated with decreases in reported sex partners, and increased alcohol
      severity was significantly associated with increases in reported sex partners.
      Increasing drug use severity was significantly associated with maintaining and
      initiating sex with a high-risk partner, while decreasing alcohol use severity
      was significantly associated with discontinuing sex under the influence. However,
      changes in drug/alcohol use severity were not associated with changes in
      unprotected sex. Substance use reductions may decrease HIV risk behaviors among
      male substance users. Our findings highlight the importance of integrating
      interventions in SUD treatment settings that address the intersection of sex risk
      behaviors and substance use.

PMID- 28513228
TI  - Relationship between CHOP/GADD153 and unstable human carotid atherosclerotic
      plaque.
AB  - BACKGROUND AND AIMS: The signaling protein C/EBP homologous protein (CHOP) and
      corresponding growth-arrest-and-DNA-damage-inducible gene 153 (GADD153) is
      associated with endoplasmic reticulum stress (ERS), which can lead to apoptosis.
      Our study aims to elucidate the role of CHOP/GADD153 in unstable atherosclerotic
      (AS) plaque formation isolated from confounding factors such as diabetes
      mellitus, primary hyperlipidemia, autoimmune deficiencies/abnormalities,
      essential hypertension, chronic heart failure, chronic kidney disease, and
      smoking. MATERIAL AND METHODS: We collected carotid artery tissue samples from
      patients aged 50-80 years-old who received carotid endarterectomies (CEA) at our
      institution. We obtained fresh AS plaque samples during CEA and preserved the
      specimens immediately in the operating room with liquid nitrogen. Samples were
      categorized as stable or unstable AS plaques according to a six-stage histologic
      classification. CHOP/GADD153 expression was then examined with
      immunohistochemistry and reverse transcription polymerase chain reaction (RT
      PCR). RESULTS: A total of 32 patients met our inclusion and exclusion criteria,
      with 24 (75.0%) classified as unstable lesions. The mean optical density ratio
      normalized to GAPDH for CHOP/GADD153 in stable and unstable groups was 0.357 +/-
      0.025 and 0.490 +/- 0.027, respectively (p < .05). Positive immunostaining of
      CHOP/GADD153 was found in macrophages and smooth muscle cells of unstable AS
      plaques with a mean integrated optical density of 0.63 +/- 0.03, compared to 0.17
      +/- 0.05 in the stable group (p < .05). CONCLUSIONS: In conclusion, we were able
      to show significant elevation of CHOP/GADD153 in unstable plaques independent of
      other confounding factors that induce ERS.

PMID- 28513229
TI  - ABO blood group is a risk factor for coronary artery disease in patients with
      poor blood pressure control.
AB  - BACKGROUND: Few studies had examined the role of ABO blood groups on CAD in
      hypertensive patients with different blood pressure (BP) controls. METHODS: A
      total of 2708 patients with primary hypertension (HTN) were consecutively
      enrolled and underwent coronary angiography (CAG) due to angina-like chest pain.
      The severity of coronary artery stenosis was assessed by Gensini score (GS).
      Patients were divided into two groups due to results of CAG: HTN with CAD (n =
      2185) and HTN without CAD (n = 523). Poor BP control was defined as systolic BP
      (SBP) >= mean in the study. Multivariable regression analysis was used to
      determine the potential impact of ABO blood groups on risk of the presence and
      severity of CAD. RESULTS: Compared to HTN without CAD group, the percentage of A
      blood group was statistically higher and O blood group was significantly lower in
      HTN with CAD group. Moreover, percentage of the angiography-proven CAD was higher
      in A blood group than that in non-A blood group (p < 0.05). After adjusting for
      confounding factors, A blood group was independently associated with CAD (odds
      ratio (OR): 1.422; 95% confidence interval (CI): 1.017-1.987; p = 0.039) and GS
      (beta = 0.055, p = 0.046) in patients with poor BP control. CONCLUSIONS: A blood
      group was an independent risk factor for the presence and severity of CAD in
      hypertensive patients with poor BP control.

PMID- 28513230
TI  - Association of renin-angiotensin-aldosterone system gene polymorphisms with left
      ventricular hypertrophy in patients with heart failure with preserved ejection
      fraction: A case-control study.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has close ties
      with hypertension, though risk factors to the development of HFpEF in
      hypertensive patients are not fully understood. Left ventricular hypertrophy
      (LVH) signifies the susceptibility toward diastolic heart dysfunction, and
      genetic determinants of LVH as a result may serve as risk predictors for HFpEF in
      hypertension. We investigated the role of three renin-angiotensin-aldosterone
      system (RAAS) gene polymorphisms in the development of LVH in hypertensive
      patients with a diagnosis of HFpEF. METHODS: A total of 176 hypertensive patients
      with a diagnosis of HFpEF were divided to cases with LVH and controls without.
      rs4343 and rs4291 of angiotensin-converting enzyme (ACE) and rs5186 of
      angiotensin receptor type 1 were genotyped using PCR-RFLP method. RESULTS:
      Genotypes and allele frequencies were significantly different between the case
      and control groups for rs4343 and rs4291, whereas no difference was observed for
      rs5186. CONCLUSION: Increased ACE activity explains the significant association
      of rs4343 and rs4291 polymorphisms with LVH in the carriers. Furthermore,
      findings support the pathophysiologic links between RAAS and increased LV mass in
      hypertension and suggest a genetic susceptibility to HFpEF. Such polymorphisms
      may serve as risk predictors of HFpEF in hypertensive patients.

PMID- 28513231
TI  - Left atrial mechanical function and stiffness in patients with nondipper
      hypertension: A speckle tracking study.
AB  - BACKGROUND: Nondipper hypertension is associated with increased cardiovascular
      morbidity and mortality. Speckle tracking echocardiography is a novel and
      promising tool for detecting early changes in left atrial (LA) myocardial
      dysfunction. Our aim was to evaluate the LA mechanical function and stiffness in
      nondipper hypertensive patients by two-dimensional speckle tracking
      echocardiography strain parameters. METHOD: This study included 80 hypertensive
      patients. Hypertensive patients were divided into two groups: 50 dipper patients
      (29 male, mean age 51.5 +/- 8 years) and 30 nondipper patients (17 male, mean age
      50.6 +/- 5.4 years). LA volume indices, mitral annular velocities, and global
      longitudinal LA strain were measured. The ratio of E/e' to LA strain was used as
      an index of LA stiffness. RESULTS: Patients with nondipper hypertension showed
      increased LA volume indices and decreased LA global strain (25.3 +/- 5.5 vs. 39.6
      +/- 9.9%, P < 0.001). LA stiffness was increased in patients with nondipper than
      in the dipper subjects (0.41 +/- 0.15 vs. 0.19 +/- 0.14, P < 0.001), and LA
      strain and LA stiffness were related to LA volume indices. CONCLUSION: Patients
      with nondipper hypertension have decreased LA global strain and increased
      stiffness, in comparison with dipper group. LA stiffness and LA strain were
      significantly related to LA volume indices. LA stiffness and LA strain can be
      used for the assessment of LA function in patients with nondipper hypertension.

PMID- 28513232
TI  - Right ventricular pressure elevated in one-kidney, one clip Goldblatt
      hypertensive rats.
AB  - Both renal and respiratory diseases are common with high mortality rate around
      the world. This study was the first to compare effects of two kidneys, one clip
      (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right
      ventricular pressure during normal condition and mechanical ventilation with
      hypoxia gas. Male Sprague-Dawley rats were subjected to control, 2K1C, or 1K1C
      groups. Twenty-eight days after the first surgery, animals were anesthetized, and
      femoral artery and vein, and right ventricle cannulated. Systemic arterial
      pressure and right ventricular systolic pressures (RVSP) were recorded during
      ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was
      significantly more than the control and 2K1C groups during baseline conditions
      and ventilation the animals with hypoxic gas. Administration of antioxidant
      Trolox increased RVSP in the 1K1C and control groups compared with their
      baselines. Furthermore, there was no alteration in RVSP during hypoxia in the
      presence of Trolox. This study indicated that RVSP only increased after 28 days
      induction of 1K1C but not 2K1C model. In addition, it seems that the response to
      hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest
      that effects of 1K1C may partially be related to reactive oxygen species (ROS)
      pathways.

PMID- 28513233
TI  - Effect of statins on blood pressure: Analysis on adverse events released by FDA.
AB  - OBJECTIVE: As a class of cholesterol-lowering drugs, statins have been reported
      to cause unexpected decrease in blood pressure (BP). However, most studies in
      this issue were subject to inadequate study design or very small sample size. The
      present study was designed to examine the BP-lowering effect of various statins.
      METHODS: Here we retrieved 5.9 million clinical reports submitted to FDA Adverse
      Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to
      estimate the overall reporting odds ratio (ROR) of hypotension adverse events
      concurrent with various statins (i.e., atorvastatin, simvastatin, and
      rosuvastatin). RESULTS: Comparing the reporting rate of hypotension event between
      statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p
      value = 8.60 * 10-4) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16
      * 10-45) were significantly associated with reduction in BP. On the other hand,
      the association between rosuvastatin and hypotension was observed to be
      nonsignificant (adjusted p-value = 0.65). CONCLUSION: To our knowledge, this is
      the first pooled analysis on large-scale data of adverse events to identify the
      BP-lowering effect of statins. The results will contribute to the development of
      novel statin-based antihypertensive therapies. In addition, the differential
      effects of individual statins can warrant subsequent research on the underlying
      mechanisms of BP control.

PMID- 28513234
TI  - The development of the UK National Institute of Health and Care Excellence
      evidence-based clinical guidelines on motor neurone disease.
AB  - The care of people with motor neuron disease/amyotrophic lateral sclerosis is
      often complex and involves a wide multidisciplinary team approach. The National
      Institute for Health and Care Excellence (NICE) in the UK has produced an
      evidence based guideline for the management of patients. This has made
      recommendations, based on clear evidence or consensus discussion. The evidence is
      often limited and areas for further research are suggested.

PMID- 28513235
TI  - Impact of interaction between CYP1A1 genetic polymorphisms and smoking on
      coronary artery disease in the Han of China.
AB  - AIMS: To investigate the association of CYP1A1 genotype and additional gene
      smoking interaction with coronary artery disease (CAD) risk based on a Chinese
      case-control study. METHODS: A total of 1862 participants (1134 men, 728 women)
      were selected, including 620 CAD patients and 1242 normal controls. Logistic
      regression was performed to investigate association of CYP1A1 genotype, gene
      gene, and gene-smoking interaction with CAD. Generalized multifactor
      dimensionality reduction (GMDR) was used to screen the best gene-gene and gene
      smoking interaction combination, cross-validation consistency, the testing
      balanced accuracy, and the sign test, to assess if each selected interaction was
      calculated. RESULTS: The carriers of homozygous mutant of rs4886605 polymorphism
      and heterozygous of rs4646903 are associated with increased CAD risk than those
      with wild-type homozygotes; OR (95% CI) was 1.98 (1.53-2.61) and 1.58 (1.24
      1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism
      is associated with decreased CAD risk than those with wild-type homozygotes, OR
      (95% CI) = 0.75 (0.60-0.93). GMDR model indicated a potential gene-gene
      interaction between rs4886605 and rs4646903 and a potential gene-smoking
      interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT
      and rs4646903-TC or CC genotype have the highest CAD risk, compared to
      participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72
      (2.03-3.61). In addition, we also found that smokers with rs4886605-CT or TT
      genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC
      genotype; OR (95% CI) was 3.07 (2.23-3.96). CONCLUSIONS: rs4886605 and rs4646903
      are associated with increased CAD risk, but rs1048943 is associated with
      decreased CAD risk; we also found gene-gene interaction between rs4886605 and
      rs4646903 and gene-environment interaction between rs4886605 and smoking.

PMID- 28513236
TI  - Enhanced gap junctional channel activity between vascular smooth muscle cells in
      cerebral artery of spontaneously hypertensive rats.
AB  - The aim of the present study is to investigate the effects of hypertension on the
      gap junctions between vascular smooth muscle cells (VSMCs) in the cerebral
      arteries (CAs) of spontaneously hypertensive rats (SHRs). The functions of gap
      junctions in the CAs of VSMCs in SHRs and control normotensive Wistar-Kyoto (WKY)
      rats were studied using whole-cell patch clamp recordings and pressure myography,
      and the expression levels of connexins were analyzed using reverse transcription
      quantitative polymerase chain reaction and Western blot analyses. Whole-cell
      patch clamp measurements revealed that the membrane capacitance and conductance
      of in situ VSMCs in the CAs were significantly greater in SHRs than in WKY rats,
      suggesting that gap junction coupling is enhanced between VSMCs in the CAs of
      SHRs. Application of the endothelium-independent vasoconstrictors KCl or
      phenylephrine (PE) stimulated a greater vasoconstriction in the CAs of SHRs than
      in those of WKY rats. The EC50 value of KCl was 24.9 mM (n = 14) and 36.9 mM
      (n=12) for SHRs and WKY rats, respectively. The EC50 value of PE was 0.9 uM (n =
      7) and 2.2 uM (n = 7) for SHRs and WKY rats, respectively. Gap junction
      inhibitors 18beta-glycyrrhetinic acid (18beta-GA), niflumic acid (NFA), and 2
      aminoethoxydiphenyl borate (2-APB) attenuated KCl-induced vasoconstriction in
      SHRs and WKY rats. The mRNA and protein expression levels of the gap junction
      protein connexin 45 (Cx45) were significantly higher in the CAs of SHRs than in
      those of WKY rats. Phosphorylated Cx43 protein expression was significantly
      higher in the CAs of SHRs than in those of WKY rats, despite the total Cx43 mRNA
      and protein expression levels in the cerebral artery (CA) exhibiting no
      significant difference between SHRs and WKY rats. Increases in the expression of
      Cx45 and phosphorylation of Cx43 may promote gap junction communication among
      VSMCs in the CAs of SHRs, which may enhance the contractile response of the CA to
      vasoconstrictors.

PMID- 28513237
TI  - T-cell subsets are associated with serum homocysteine concentration in patients
      with essential hypertension.
AB  - OBJECTIVE: To explore the association between serum homocysteine (Hcy)
      concentration and T-cell subsets from patients with essential hypertension.
      PATIENTS AND METHODS: A total of 218 essential hypertension patients were
      recruited, of which 170 were H-type essential hypertensive and 48 were non-H-type
      essential hypertensive. H-type essential hypertensive patients were divided into
      three groups by concentration of serum Hcy. The peripheral blood T-cell subsets
      (CD3+%, CD4+%, CD8+ T%, CD4+/CD8+) and clinical features including age, sex,
      serum creatinine, uric acid, total cholesterol, triglycerides, low-density
      lipoprotein cholesterol, and high-density lipoprotein cholesterol were recorded
      and analyzed with T-cell subsets which were counted by fluorescence activated
      cytometry. RESULTS: Compared with non-H-type hypertensive patients, CD4+ T-cell
      percentage in peripheral blood was significantly decreased in H-type hypertensive
      patients. Because of the increase of Hcy level, CD4+ T-cell percentage decreased.
      Linear regression analysis showed that Hcy level was negatively correlated with
      CD4+ T-cell percentage; however, it was positively correlated with CD3+ T-cell
      percentage. CONCLUSION: A direct association between serum Hcy concentrations and
      T-cell percentage was observed in patients with essential hypertension. This
      observation indicates that T-cell subsets might play an important role in
      hypertension.

PMID- 28513238
TI  - Exercise and Dementia in Nursing Homes: Views of Staff and Family Carers.
AB  - This paper reports the qualitative component of a randomized controlled trial
      which evaluated the impact and feasibility of a physical exercise intervention on
      individuals living with dementia in nursing homes. Interviews were conducted with
      10 staff and nine family carers about their views and opinions of physical
      exercise (n = 19). Thematic content analysis revealed both benefits and barriers
      to physical exercise for individuals living with dementia in nursing homes.
      Another theme was the influences of knowledge and understanding on individuals'
      views of physical exercise. The involvement of staff and family carers in
      research encourage their involvement in the implementation of research into
      clinical practice. This can help to improve provisions of meaningful and
      beneficial activities for individuals living with dementia in nursing homes. The
      views and opinions of individuals living with dementia in nursing homes were not
      considered, though it would be beneficial to include them in future research.

PMID- 28513239
TI  - Multicenter evaluation of IV acyclovir use prior to, during, and after a national
      shortage.

PMID- 28513240
TI  - Prenatal diagnosis of monosomy 18p associated with holoprosencephaly: case
      report.

PMID- 28513241
TI  - Eric T MacKenzie, PhD (25 May 1950-2 March 2017).

PMID- 28513242
TI  - Development of Physical Activity-Related Parenting Practices Scales for Urban
      Chinese Parents of Preschoolers: Confirmatory Factor Analysis and Reliability.
AB  - BACKGROUND: Valid instruments of parenting practices related to children's
      physical activity (PA) are essential to understand how parents affect
      preschoolers' PA. This study developed and validated a questionnaire of PA
      related parenting practices for Chinese-speaking parents of preschoolers in Hong
      Kong. METHODS: Parents (n = 394) completed a questionnaire developed using
      findings from formative qualitative research and literature searches. Test-retest
      reliability was determined on a subsample (n = 61). Factorial validity was
      assessed using confirmatory factor analysis. Subscale internal consistency was
      determined. RESULTS: The scale of parenting practices encouraging PA comprised 2
      latent factors: Modeling, structure and participatory engagement in PA (23
      items), and Provision of appropriate places for child's PA (4 items). The scale
      of parenting practices discouraging PA scale encompassed 4 latent factors: Safety
      concern/overprotection (6 items), Psychological/behavioral control (5 items),
      Promoting inactivity (4 items), and Promoting screen time (2 items). Test-retest
      reliabilities were moderate to excellent (0.58 to 0.82), and internal subscale
      reliabilities were acceptable (0.63 to 0.89). CONCLUSION: We developed a theory
      based questionnaire for assessing PA-related parenting practices among Chinese
      speaking parents of Hong Kong preschoolers. While some items were context and
      culture specific, many were similar to those previously found in other
      populations, indicating a degree of construct generalizability across cultures.

PMID- 28513243
TI  - Performance of Alpine Touring Boots When Used in Alpine Ski Bindings.
AB  - Alpine touring (AT) equipment is designed for ascending mountains and snow skiing
      down backcountry terrain. Skiers have been observed using AT boots in alpine (not
      made for Alpine Touring) ski bindings. We tested the effect on the retention
      release characteristics of AT boots used in alpine bindings. Ten AT ski boots and
      5 alpine ski boots were tested in 8 models of alpine ski bindings using an ASTM
      F504-05 (2012) apparatus. Thirty-one percent of the AT boots released
      appropriately when used in alpine ski bindings. One alpine binding released
      appropriately for all alpine and AT boots tested; 2 alpine ski bindings did not
      release appropriately for any AT boots. Altering the visual indicator settings on
      the bindings (that control the release torque of an alpine system) had little or
      no effect on the release torque when using AT boots in alpine ski bindings. Many
      combinations released appropriately in ski shop tests, but did not release
      appropriately in the more complex loading cases that simulated forward and
      backward falls; the simple tests performed by ski shops could produce a "false
      negative" test result. These results indicate that using AT boots with alpine ski
      bindings could increase the likelihood of lower leg injuries.

PMID- 28513244
TI  - Different Relationship Between Physical Activity, Arterial Stiffness, and
      Metabolic Status in Obese Subjects.
AB  - BACKGROUND: Although the relationship between physical activity and arterial
      stiffness has been shown in healthy persons, it remains controversial in obese
      persons. METHODS: From January 2014 to September 2014, we evaluated 795 obese
      subjects from 25 public health centers in Seoul, Korea. We compared physical
      activity and brachial-ankle pulse wave velocity (baPWV) between obese subjects
      with metabolic syndrome (MetS) (MO) and obese subjects without MetS (NMO).
      RESULTS: The MO group had more men, higher body mass index (BMI), higher fasting
      glucose level, lower high-density lipoprotein-cholesterol level, and higher
      triglyceride level. The mean physical activity levels were similar between the 2
      groups. baPWV was higher in the MO group than the NMO group. MO group showed
      positive correlation between baPWV and physical activity (Ptrend = 0.04).
      Interestingly, baPWV was significantly higher in the MO group than in the NMO
      group in subjects with moderate and vigorous physical activity (1403.4 cm/sec vs
      1349 cm/sec [95% CI 21.4 to 87.4], P < .05). Multivariate regression analysis
      demonstrated that brachial-ankle pulse wave velocity was apparently associated
      with age, BMI, blood pressure, and glucose level. CONCLUSIONS: In a community
      based population, baPWV was higher in obese MetS group compared with obese non
      MetS group. Physical activity showed different association with baPWV depending
      on metabolic status.

PMID- 28513245
TI  - Sit-Stand Desks To Reduce Workplace Sitting Time In Office Workers With Abdominal
      Obesity: A Randomized Controlled Trial.
AB  - BACKGROUND: Sit-stand desks reduce workplace sitting time among healthy office
      workers; however, their metabolic and behavioral impact in higher risk
      populations remains unknown. METHODS: 25 office workers with abdominal obesity
      were randomized to an intervention (sit-stand workstation) or control group
      (seated desk) for 12 weeks. Physical activity, sedentary behavior, and
      cardiometabolic risk factors were assessed before and after the intervention
      period in both groups. RESULTS: In comparison with the control group, which did
      not change, the intervention group experienced significant reductions in workday
      (344 +/- 107 to 186 +/- 101 min/day) and total (645 +/- 140 to 528 +/- 91
      min/day) sitting time, as well as increases in workday standing time (154 +/- 108
      to 301 +/- 101 min/day, P < .05). There were no changes in sitting or standing
      time outside of work hours, steps taken each day, or any marker of
      cardiometabolic risk in either group (all P > .05). CONCLUSION: Sit-stand desks
      were effective in reducing workplace sedentary behavior in an at-risk population,
      with no change in sedentary behavior or physical activity outside of work hours.
      However, these changes were not sufficient to improve markers of cardiometabolic
      risk in this population.

PMID- 28513247
TI  - Use of nonbiologic treatments in antihistamine-refractory chronic urticaria: a
      review of published evidence.
AB  - BACKGROUND: Knowledge of effectiveness and safety of the nonbiologic,
      nonantihistamine treatments used for chronic urticaria is important as in some
      cases the principal guideline-recommended drug; omalizumab, has limited effect,
      side effects or is too expensive or unavailable. Herein, we systematically review
      the evidence for the use of the nonbiologic treatments in antihistamine
      refractory chronic urticaria. METHODS: We performed a systematic review of the
      literature using PubMed and Webofscience and identified studies that reported use
      of one or more of the nonbiological, nonantihistamine treatment options for
      chronic urticaria. The studies were evaluated based on study design, number of
      patients, effect of treatment and safety. RESULTS: We identified 118 studies or
      case series with 13 different treatments (azathioprine, chloroquine, colchicine,
      cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate,
      montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic
      acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a
      paucity of controlled trials for most of the treatments reviewed albeit the
      strongest evidence in favor of a beneficial effect in chronic urticaria was,
      apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed
      by IVIG. CONCLUSION: The treatment options reviewed should be seen as potential
      alternatives in treatment-resistant chronic urticaria where guideline-based
      selections have failed. However, larger controlled trials are warranted to
      advance the level of evidence, possibly supporting some treatments' future
      recommendation in selected patients.

PMID- 28513248
TI  - The Comparative Effects of Ankle Bracing on Functional Performance.
AB  - Ankle sprains represent a common musculoskeletal injury that clinicians are
      tasked with preventing and treating. Because of the prevalence of this injury,
      ankle braces have been designed to prophylactically protect the joint and reduce
      the incidence of repetitive sprains. Although an abundance of literature exists
      focusing on the efficacy of braces in preventing ankle sprains in young, healthy,
      and physically active populations, there is a scarcity of evidence specific to
      the impact of these apparatuses on functional performance; therefore, the purpose
      of this critically appraised topic (CAT) is to investigate the effects of ankle
      braces on functional performance measures in such individuals. The outcomes of
      this CAT will assist sport rehabilitation specialists with informed clinical
      decision making in managing young, healthy, and physically active populations
      using ankle braces. Do ankle braces hinder functional performance measures when
      compared with an unbraced condition in a young, healthy, and physically active
      population? A minimum of level II evidence research studies were surveyed for
      this CAT. For this CAT, 1 randomized controlled trial and 3 prospective cohort
      studies were selected. One study found a statistically significant main effect of
      increased agility run times while participants wore ankle braces. Another study
      demonstrated a statistically significant decrease in vertical jump height and
      ankle range of motion while wearing braces. No other statistically significant
      findings were reported among studies comparing unbraced with braced conditions.
      Current data indicate that young, healthy, and physically active individuals may
      experience varied performance effects when executing specific functional
      performance tasks while wearing ankle braces. In general, bracing does not appear
      to significantly impair performance on most functional tasks; however, decrements
      were noted to increases in agility run time and decreases in vertical jump
      height. Subsequent analysis indicated that a brace may result in decreased ankle
      plantarflexion, dorsiflexion, eversion, and inversion range of motion, which may
      underpin noted performance deficits.

PMID- 28513246
TI  - Molecular composition and distribution of gap junctions in the sensory epithelium
      of the human cochlea-a super-resolution structured illumination microscopy (SR
      SIM) study.
AB  - BACKGROUND: Mutations in the GJB2 gene, which encodes the Connexin26 (Cx26)
      protein, are the most common cause of childhood hearing loss in American and
      European populations. The cochlea contains a gap junction (GJ) network in the
      sensory epithelium and two connective tissue networks in the lateral wall and
      spiral limbus. The syncytia contain the GJ proteins beta 2 (GJB2/Cx26) and beta 6
      (GJB6/Cx30). Our knowledge of their expression in humans is insufficient due to
      the limited availability of tissue. Here, we sought to establish the molecular
      arrangement of GJs in the epithelial network of the human cochlea using
      surgically obtained samples. METHODS: We analyzed Cx26 and Cx30 expression in GJ
      networks in well-preserved adult human auditory sensory epithelium using
      confocal, electron, and super-resolution structured illumination microscopy (SR
      SIM). RESULTS: Cx30 plaques (<5 MUm) dominated, while Cx26 plaques were subtle
      and appeared as 'mini-junctions' (2-300 nm). 3-D volume rendering of Z-stacks and
      orthogonal projections from single optical sections suggested that the GJs are
      homomeric/homotypic and consist of assemblies of identical GJs composed of either
      Cx26 or Cx30. Occasionally, the two protein types were co-expressed, suggesting
      functional cooperation. CONCLUSIONS: Establishing the molecular composition and
      distribution of the GJ networks in the human cochlea may increase our
      understanding of the pathophysiology of Cx-related hearing loss. This information
      may also assist in developing future strategies to treat genetic hearing loss.

PMID- 28513249
TI  - Medicaid Expansion Produces Long-Term Impact on Insurance Coverage Rates in
      Community Health Centers.
AB  - BACKGROUND: It is crucial to understand the impact of the Affordable Care Act
      (ACA). This study assesses changes in insurance status of patients visiting
      community health centers (CHCs) comparing states that expanded Medicaid to those
      that did not. METHODS: Electronic health record data on 875,571 patients aged 19
      to 64 years with >= 1 visit between 2012 and 2015 in 412 primary care CHCs in 9
      expansion and 4 nonexpansion states. We assessed changes in rates of total,
      uninsured, Medicaid-insured, and privately insured primary care and preventive
      care visits; immunizations administered, and medications ordered. RESULTS: Rates
      of uninsured visits decreased pre- to post-ACA, with greater drops in expansion (
      57%) versus nonexpansion (-20%) states. Medicaid-insured visits increased 60% in
      expansion states while remaining unchanged in nonexpansion states. Privately
      insured visits were 2.7 times higher post-ACA in nonexpansion states with no
      increase in expansion states. Comparing 2015 with 2014: Uninsured visit rates
      continued to decrease in expansion (-28%) and nonexpansion states (-19%),
      Medicaid-insured rates did not significantly increase, and privately insured
      visits increased in nonexpansion states but did not change in expansion states.
      CONCLUSIONS: Medicaid expansion and subsidies to purchase private coverage likely
      increased the accessibility of health insurance for patients who had previously
      not been able to access coverage.

PMID- 28513251
TI  - Comparison of the effects of 665 nm low level diode Laser Hat versus and a
      combination of 665 nm and 808nm low level diode Laser Scanner of hair growth in
      androgenic alopecia.
AB  - BACKGROUND: This study aimed to evaluate the effectiveness of a combined set of
      low level diode laser scanner (665 nm and 808nm) on hair growth, and assessment
      of safety and effectiveness of a new laser scanner on hair growth treatment
      procedure in androgenic alopecia. METHODS: 90 patients (18 to 70 years) with
      androgenic alopecia were randomized into three groups. The first group (n=30)
      received 655 nm red light using laser hat, the second group (n=30) received 655
      nm red laser plus 808 nm infrared laser using a laser scanner of hair growth
      device (with the patent number: 77733) and the third group (n=30) received no
      laser as the control group. RESULTS: Patients in laser scanner group had better
      results and showed a higher increase in terminal hair density compared with laser
      hat group (mean of 9.61 versus 9.16 per cm2). We found significant decrease in
      terminal hair density from baseline in control group (mean -1.8 per cm2,
      p<0.0001). CONCLUSION: Results showed a statistically significant improvement in
      the laser scanner of the hair growth group compared with laser hat and the
      control group. The study showed that treatment with new laser devise had a
      promising result without any observable adverse effects.

PMID- 28513250
TI  - Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide
      levels for assessing upper airway diseases in asthmatic patients.
AB  - BACKGROUND: Despite the close linkage between rhinitis, chronic rhinosinusitis
      (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation
      are rare. METHODS: Patients with asthma (without upper airway disease [UAD; n =
      24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated
      rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were
      prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s
      (FeNO50), nasal NO levels, Lund-Macay-scores of sinus computed tomography and an
      asthma control questionnaire (ACQ) were evaluated. RESULTS: Asthma was associated
      with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were
      higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2
      ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were
      higher in rhinitis patients than other UAD categories, irrespective of the asthma
      concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb)
      than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p <
      0.0001). A receiver-operating-characteristic curve analysis for detecting
      comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve
      (0.87). Nasal NO levels were positively correlated with FeNO50 levels (rho =
      0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively
      correlated with the Lund-Macay (rho = -0.46, p = 0.03) and ACQ scores (rho = 
      0.52, p = 0.009) in asthmatics with CRS. CONCLUSIONS: Higher nasal NO levels
      reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO50
      levels reflect the presence of CRS and asthma. These NO measurements are useful
      for assessing comorbid UAD in asthmatics.

PMID- 28513252
TI  - A novel model-based on FCM-LM algorithm for prediction of protein folding rate.
AB  - The prediction of protein folding rates is of paramount importance in describing
      the protein folding mechanism, which has broad applications in fields such as
      enzyme engineering and protein engineering. Therefore, predicting protein folding
      rates using the first-order of protein sequence, secondary structure and amino
      acid properties has become a very active research topic in recent years. This
      paper presents a new fuzzy cognitive map (FCM) model based on deep learning
      neural networks which uses data obtained from biological experiments to predict
      the protein folding rate. FCM extracts the important data features from the
      protein sequence which then initializes the deep neural networks effectively. It
      was found that the Levenberg-Marquardt (LM) algorithm for deep neural networks
      can improve the prediction accuracy of the protein folding rates. The correlation
      coefficient between the predicted values and those real values obtained from
      experiments reached 0.94 and 0.9 in two independent numerical tests.

PMID- 28513253
TI  - Synthesizing large-scale species trees using the strict consensus approach.
AB  - Supertree problems are a standard tool for synthesizing large-scale species trees
      from a given collection of gene trees under some problem-specific objective.
      Unfortunately, these problems are typically NP-hard, and often remain so when
      their instances are restricted to rooted gene trees sampled from the same
      species. While a class of restricted supertree problems has been effectively
      addressed by the parameterized strict consensus approach, in practice, most gene
      trees are unrooted and sampled from different species. Here, we overcome this
      stringent limitation by describing efficient algorithms that are adopting the
      strict consensus approach to also handle unrestricted supertree problems.
      Finally, we demonstrate the performance of our algorithms in a comparative study
      with classic supertree heuristics using simulated and empirical data sets.

PMID- 28513254
TI  - Peripapillary sparing in RDH12-associated Leber congenital amaurosis.
AB  - BACKGROUND: Peripapillary sparing is a characteristic that is traditionally
      described as pathognomonic for Stargardt disease. MATERIALS AND METHODS: We
      present a multimodal assessment of four Leber congenital amaurosis (LCA) cases
      with congenital macular atrophy and severely attenuated electroretinogram
      findings caused by bilallelic mutations in RDH12. RESULTS: Fundus
      autofluorescence imaging revealed a general loss of retinal pigment epithelium
      across the macula except for the peripapillary region in both eyes of all
      patients. Spectral domain-optical coherence tomography confirmed relative
      preservation in this area along with retinal thinning and excavation throughout
      the rest of the macula. LCA was diagnosed based on clinical exam and retinal
      imaging, and subsequently confirmed with genetic testing. CONCLUSIONS:
      Peripapillary sparing is a novel phenotypic feature of RDH12-associated LCA.

PMID- 28513255
TI  - Successful mechanical thrombectomy in a comatose patient with cerebral venous
      sinus thrombosis: A case report.
AB  - Cerebral venous sinus thrombosis is a rare cause of stroke, which is routinely
      treated with systemic heparin. Unfavourable outcome is often seen in severe
      cases. Therefore alternative treatment methods should be explored in these
      patients. Due to the risk of haemorrhagic complications, treatment without
      administration of thrombolytics is of particular interest. This report presents a
      case of successful mechanical thrombectomy, without the use of thrombolytics, in
      a comatose patient with cerebral venous sinus thrombosis.

PMID- 28513256
TI  - Do current OELs for silica protect from obstructive lung impairment? A critical
      review of epidemiological data.
AB  - Inhalation of respirable crystalline silica (RCS) can lead to serious health
      effects such as silicosis and lung cancer. There also seems to be a general
      consensus to consider that RCS exposure is associated with obstructive lung
      impairment or chronic obstructive pulmonary disease (COPD), a leading cause of
      mortality, morbidity, and disability worldwide. It is, however, not clear whether
      occupational exposure levels (OELs), generally set to prevent silicosis, also
      protect workers from developing an obstructive impairment. This review aims at
      clarifying the potential relationship between RCS exposure and obstructive lung
      impairment as defined by spirometry. Eleven studies that reported both silica
      exposure levels and spirometry results were identified. We systematically
      extracted data pertaining to (a) the population studied, (b) level of exposure to
      RCS and other pollutants, (c) spirometry procedure and interpretation, and (d)
      methodology used to investigate the relationship between RCS exposure and
      spirometry. These studies add supporting evidence in favor of a qualitative
      association between occupational activities exposing to RCS and obstructive lung
      dysfunction. However, no well-founded quantitative estimate can be drawn from
      these investigations; the available relevant literature does not allow defining a
      RCS exposure threshold associated with an increased risk of obstructive lung
      dysfunction, as defined by spirometry, in workers without silicosis. Further
      research is needed, but, as highlighted in this review, conducting
      epidemiological studies with both valid exposure and outcome measurements is a
      real challenge.

PMID- 28513257
TI  - Factors Associated With Levels of Physical Activity in Chronic Kidney Disease
      Patients Undergoing Hemodialysis: The Role of Dialysis Versus Nondialysis Day.
AB  - BACKGROUND: Patients on hemodialysis (HD) report lower physical activity (PA)
      levels. We analyzed factors associated with low levels of PA in patients with
      chronic kidney disease (CKD) and compared PA on HD day and non-HD. METHODS: 79
      patients wore an accelerometer and were classified according to time spent on
      moderate-to-vigorous PA (MVPA). Demographic data, BMI, comorbidities, clinical
      status, and health-related quality of life (HRQoL) were checked for association
      with PA. In addition, PA level was compared between days of HD and non-HD.
      RESULTS: Accelerometer compliance was 78.5% [33 men and 29 women (53.96 +/- 15.71
      yrs) were included in analysis]. 35.5% of sample achieved >=150min/week on MVPA.
      Lower MVPA was associated with older age (OR = 5.80, 95% CI = 1.11 to 30.19, P =
      .04), and lower score of physical function HRQoL (OR = 4.33, 95% CI = 1.23 to
      15.23, P = .02). In addition, patients spent 9.73% more time on sedentary
      behavior, 38.9% less on light PA and 74.9% less on MVPA on HD day versus non-HD
      day. CONCLUSION: Age and physical function HRQoL were the main factors associated
      to lower PA levels. In addition, lower time spent on PA during HD day suggest
      that strategies for increasing physical activity levels during HD day such
      exercising during HD session could help CKD patients to reach current PA
      recommendations.

PMID- 28513258
TI  - A Note from the Outgoing Editor.

PMID- 28513260
TI  - Standing on the Shoulders of Nutrition's Giants: A Third Editor Assumes the Food
      and Nutrition Bulletin.

PMID- 28513259
TI  - Short Stature Is Associated With Overweight but Not With High Energy Intake in
      Low-Income Quilombola Women.
AB  - BACKGROUND: Population exposed to chronic undernutrition in early life seems to
      be more susceptible to obesity in adulthood due to the development of mechanisms
      that improve the efficiency of energy use. Therefore, these individuals have
      relatively reduced energy requirements (thrifty phenotype). OBJECTIVE: To
      investigate, among women living on severe socioeconomic vulnerability, whether
      short stature, a marker for undernutrition in early life, is associated with
      excess body weight but not with a high energy intake. METHODS: This cross
      sectional study, carried out between July and November 2008, evaluated 1308 women
      from all (N = 39) Quilombola communities of Alagoas. Adequacy of energy intake
      was estimated by the ratio between energetic ingestion and the estimated energy
      requirement (EER). RESULTS: The prevalence of short stature (<= 154.8 cm) was
      43.0% and 52.4% had excess body weight (body mass index >= 25 kg/m2), being that
      33.1% were overweight and 19.3% obese. Excess body weight was higher among women
      with short stature (56.6% vs 49.2%; P = .008), even after adjusting for age,
      energy intake, and per capita income (prevalence ratio = 1.16; 95% confidence
      interval = 1.04; 1.28). The ratio of energy intake/EER was independent of women's
      stature. CONCLUSION: Excess body weight among Quilombola women represents a
      serious health problem. Short stature was significantly associated with excess
      body weight but not with a high energy intake. "Thrifty phenotype" may be one of
      the plausible explanations for this finding.

PMID- 28513261
TI  - Rainer Gross Award Lecture 2016: A Laboratory in Your Pocket: Enabling Precision
      Nutrition.
AB  - The need for improving methods of nutritional assessment and delivering primary
      health care globally cannot be overemphasized. While advances in medical
      technology typically create more disparities because of access being limited to
      resource-rich settings, a transition of health care to a mobile platform is
      increasingly leveling the field. Technological advances offer opportunities to
      scale laboratory procedures down to mobile devices, such as smartphones and
      tablets. Globalization also provides the required infrastructure and network
      capacity to support the use of mobile health devices in developing settings where
      nutritional deficiencies are most prevalent. Here, we discuss some of the
      applications and advantages provided by expanding markets of biomarker
      measurement coupled with primary health care and public health systems and how
      this is enhancing access and delivery of health services with significant global
      impact.

PMID- 28513262
TI  - Introduction to Rainer Gross.

PMID- 28513263
TI  - Mortality Benefits of Vitamin A Are Not Affected by Varying Frequency, Total
      Dose, or Duration of Supplementation.
AB  - BACKGROUND: Although vitamin A supplementation reduces child mortality, it
      remains unclear whether dosing frequency, total dose, or duration modifies
      effectiveness. OBJECTIVE: Determine whether mortality effects of vitamin A vary
      by dosing frequency, total dose, or duration. METHODS: Meta-analysis of
      randomized controlled trials, identified by systematic review and expert opinion,
      utilizing relatively standard World Health Organization doses in children <5
      years. Meta-regression evaluated whether mortality effects varied by dosing
      frequency, total dose, or supplementation duration. RESULTS: Identified 17
      trials, including 1,180,718 children, mean (standard deviation [SD]) age 31.5
      (15.4) months at baseline. Supplementation frequency ranged every 3 months-every
      2 years, supplementation duration 4-60 months (mean = 15.4; SD = 12.8), and total
      dose 134,361-2,200,000 IU (mean = 667,132 IU; SD = 540,795). Compared with
      control, vitamin A reduced mortality 22% (95% confidence interval [CI] = 10-32; P
      = 0.002). This protective effect was not modified by increasing supplementation
      frequency (dose/year: relative risk [RR] = 1.02; 95% CI = 0.98-1.06; P = .22),
      total dose (per 200,000 IU: RR = 1.02; 95% CI = 0.97-1.06; P = .31), nor
      supplementation duration (per year: RR = 1.06; 95% CI = 0.97-1.15; P = 0.14).
      Multivariate meta-regression showed similar results. Sensitivity analyses
      excluding 1 controversial trial (Aswathi 2013) did not alter findings.
      CONCLUSION: Results confirm benefits of vitamin A supplementation in children <5
      years in nations with vitamin A deficiency, without influence of frequency, total
      dose, or dosing duration within ranges evaluated. These findings inform design
      and efficiency of vitamin A supplementation policies.

PMID- 28513265
TI  - Perturbing Status of Vitamin B12 in Indian Infants and Their Mothers.
AB  - BACKGROUND: Vitamin B12 deficiency in early life can adversely affect the growth
      of developing brain with myriad of neurodevelopmental manifestations. At this
      age, the deficiency is usually the result of low maternal levels. OBJECTIVES: To
      assess the vitamin B12 status of healthy exclusively breast-fed Indian infants
      aged 1 to 6 months and their mothers. METHODS: One hundred term exclusively
      breast-fed infants aged 1 to 6 months attending pediatric outpatient department
      were recruited. Hemogram, serum B12, folate, and ferritin levels were obtained
      from each infant-mother pair. RESULTS: The prevalence of B12 deficiency in
      infants was found to be 57%. Forty-six percent of mothers were deficient. There
      was a positive correlation ( r = .23) between the B12 levels of the infants and
      their mothers. CONCLUSION: There is a high prevalence of vitamin B12 deficiency
      in Indian infants and their mothers. There is an urgent need to supplement our
      population with vitamin B12, and the best time to do this would be antenatal.

PMID- 28513264
TI  - Body Composition Analysis by Using Bioelectrical Impedance in a Young Healthy
      Chinese Population: Methodological Considerations.
AB  - OBJECTIVE: To develop a new bioelectrical impedance analysis (BIA) model for
      analyzing body composition by using isotope dilution, magnetic resonance imaging
      (MRI), and dual-energy X-ray absorptiometry (DEXA) as the reference methods in
      young healthy Chinese populations. METHODS: Thirty healthy participants were
      enrolled. Their body composition was analyzed using BIA and 3 reference methods.
      We established a model that uniformed data from 3 references methods (isotope,
      MRI, and DEXA) into 1 formula. This model was further validated with 209
      participants. RESULTS: The following BIA body composition adjustment model was
      developed: [Formula: see text], where X represents the impedance index; when K =
      1, 2, and 3, Y represents total body water, fat mass, and bone mass,
      respectively. The prediction accuracy of this formula was 93.3%. By incorporating
      the data matrix, the protein mass was calculated using BIA: [Formula: see text].
      In the verification part of this study, the lean body mass measured using DEXA
      and BIA was 43.02 +/- 8.34 kg and 45.85 +/- 8.81 kg, respectively. Analysis
      indicated that the model fit was extremely favorable ( R2 = .9997, P < .001).
      CONCLUSIONS: The accuracy of BIA measurement on body composition and protein mass
      is significantly improved by our work.

PMID- 28513266
TI  - A Technical and Policy Case Study of Large-Scale Rescue and Redistribution of
      Perishable Foods by the "Leket Israel" Food Bank.
AB  - BACKGROUND: Food banks seeking to rescue and redistribute highly nutritious
      perishable foods to simultaneously alleviate food insecurity and reduce food
      waste often encounter practical, ethical, and political dilemmas. OBJECTIVES: We
      present a case study of "Leket Israel," an Israeli food bank that uses an
      effective large-scale logistical model for the rescue and redistribution of
      perishable food and discuss the challenges and solutions it offers. RESULTS: The
      organization operates in a rich country plagued with poverty and inequality,
      where the government passively encourages nongovernmental organizations to
      respond to the serious and growing problem of food insecurity. Operating under a
      business-to-business model, Leket Israel distributes food via intermediary
      nonprofit organizations (NPOs), enriching the food they provide with fresh
      produce. Food is obtained through an Agricultural Gleaning project, Self-Growing
      Farm project, and Meal Rescue project. The partnering NPOs then distribute the
      food to people in need. Although the rescue and redistribution of highly
      perishable food is more costly and complex than acquiring, storing, and
      distributing dried and staple foods and it requires specialized knowledge and
      infrastructure in order to maintain rigorous safety standards, it improves the
      nutritional quality of the aid. In 2015, Leket Israel distributed 15 217 389 kg
      of food, 90% of which was fruit and vegetables, to 180 partnering NPOs
      nationwide, reaching an estimated 175 000 recipients. CONCLUSION: "Leket Israel"
      offers a valuable model that can be studied and emulated by international
      nutrition scientists, practitioners, and policy makers who are seeking to reduce
      food insecurity and food waste in other countries.

PMID- 28513267
TI  - Self-use of snake venom: The other side of the coin.

PMID- 28513268
TI  - Effects of Volume Training on Strength and Endurance of Back Muscles: A
      Randomized Controlled Trial.
AB  - CONTEXT: Strength/resistance training volume has historically been supported in
      the American College of Sports Medicine recommendations. However, for the back
      muscles, exercise prescription related to the number of sets, such as single
      versus multiple, is not well established in the literature. OBJECTIVE: The
      purpose of this study was to compare the effects of 2 training volumes on
      strength and endurance of back-extensor muscles in untrained young participants
      with regard to a repeated-measures design. DESIGN: Randomized controlled trial.
      SETTING: Laboratory of functional evaluation and human motor performance.
      PARTICIPANTS: Forty-four untrained young participants (mean age = 21 y) were
      randomized into single-set (n = 14), multiple-set (MSG, n = 15), and untrained
      control (n = 15) groups. INTERVENTION: The single-set group and MSG underwent a
      10-week progressive resistance training program (2 d/wk) using a 45 degrees 
      Roman chair. MAIN OUTCOME MEASURES: Back maximal strength (dynamometer) and
      isometric and dynamic endurance (time limit, trunk extension-flexion cycles, and
      electromyography muscle fatigue estimates). RESULTS: The results showed
      differences between the MSG and control group for isometric endurance time (mean
      = 19.8 s; 95% confidence interval, -44.1 to 4.8), but without time intervention
      significance. Significant improvement after training (P < .05) was found
      predominantly during dynamic endurance (number of repetitions) for both the MSG
      (+61%) and single-set group (+26%) compared with preintervention, whereas the
      control group reported no benefit. There was no significant (P > .05) difference
      in either strength or electromyography estimates after training. CONCLUSIONS:
      Both multiple and single volume training were efficient in promoting better back
      endurance during dynamic performance based on mechanical variables (time and
      number of repetitions).

PMID- 28513270
TI  - Physiological and Performance Measures for Baseline Concussion Assessment.
AB  - CONTEXT: Baseline testing is a common strategy for concussion assessment and
      management. Research continues to evaluate novel measures for potential to
      improve baseline testing methods. OBJECTIVES: The primary objective was to (1)
      determine the feasibility of including physiological, neuromuscular, and mood
      measures as part of baseline concussion testing protocol, (2) describe typical
      values in a varsity athlete sample, and (3) estimate the influence of concussion
      history on these baseline measures. DESIGN: Prospective observational study.
      SETTING: Ryerson University Athletic Therapy Clinic. PARTICIPANTS: One hundred
      varsity athletes. MAIN OUTCOME MEASURES: Frequency and domain measures of heart
      rate variability, blood pressure, grip strength, profile of mood states-short
      form, and the Sport Concussion Assessment Tool-2. RESULTS: Physiological,
      neuromuscular performance, and mood measures were feasible at baseline.
      Participants with a history of 2 or more previous concussions displayed
      significantly higher diastolic blood pressure. Females reported higher total mood
      disturbance compared with males. CONCLUSIONS: Physiological and neuromuscular
      performance measures are safe and feasible as baseline concussion assessment
      outcomes. History of concussion may have an influence on diastolic blood
      pressure.

PMID- 28513271
TI  - College Pitchers Demonstrate Directional Differences in Shoulder Joint Position
      Sense Compared With Controls.
AB  - CONTEXT: The relationship between overhead throwing and its effect on
      proprioception is not well understood. It is important to gain a better
      understanding of how these are related, to protect overhead athletes from an
      increased risk of injury. OBJECTIVE: To investigate proprioceptive alterations in
      the overhead thrower's shoulder. DESIGN: Cross-sectional study. Independent
      variables are limb (dominant and nondominant), group (thrower or control), and
      target angle. Dependent variables are joint position sense and range of motion.
      SETTING: An orthopedic biomechanics lab and university athletic training
      facility. PARTICIPANTS: Twelve Division I baseball pitchers and 13 nonthrowing
      control subjects. INTERVENTION: Shoulder proprioception was assessed using an
      active joint repositioning task administered with an iPod Touch. MAIN OUTCOME
      MEASURE: Root mean square error and constant error of repositioning angles were
      used to assess accuracy and directional patterns, respectively. RESULTS: Both
      groups demonstrated significantly higher joint acuity at the 80 degrees  external
      rotation target angle compared with 60 degrees  (1.5 degrees  [0.5 degrees ], P =
      .01). There were no differences in accuracy between groups. Constant error
      revealed differing repositioning patterns between limbs for the pitchers and also
      between groups for the dominant side. Although the throwing shoulder overshot the
      target angles by 0.4 degrees , all nonthrowing shoulders undershot by an average
      of 2.7 degrees . CONCLUSIONS: There is no difference in shoulder joint position
      sense accuracy between throwers and nonthrowers, although both groups display
      increased accuracy closer to their end range of external rotation. The throwing
      shoulder demonstrates a different repositioning pattern, overshooting the desired
      target angle, while all other shoulders undershoot.

PMID- 28513273
TI  - The clinical value of Vav3 in peripheral blood for predicting lymphatic
      metastasis of gastric cancer.
AB  - BACKGROUND: Overexpression of Vav3, a gene involved in signal transduction,
      promotes invasion and inhibits apoptosis in several cancers. The clinical value
      of the protein product of this gene, Vav3, in the peripheral blood of gastric
      cancer patients is unknown. We hypothesised increased serum Vav3 that related to
      tissue levels and lymph node metastases. In addition, we further explored its
      clinical value in respect of linked molecules Rac-1, MMP-7 and ICAM-1 Methods:
      120 gastric cancer patients who had radical surgery were enrolled.
      Immunohistochemistry was used to determine the expressions of Vav3, Rac-1, MMP-7
      and ICAM-1 in gastric cancer mucosa and normal mucosa. ELISA was used to detect
      these proteins in peripheral blood of gastric cancer patients and 100 age- and
      sex-matched healthy controls. RESULTS: Vav3, Rac-1 and MMP-7 (P < 0.001), but not
      ICAM-1 (P = 0.303) were more highly expressed by cancer tissues than normal
      gastric mucosa. Serum levels of all molecules were higher than those in healthy
      subjects (P < 0.001). Levels of Vav3, Rac-1 and MMP-7 decreased 2 weeks
      postoperatively (all P < 0.001) but there was no change in ICAM-1 (P = 0.192).
      Similarly, increased levels of Vav3, Rac-1 and MMP-7 were present in patients
      with lymphatic metastasis than those without (all P < 0.001) but there was no
      difference in ICAM-1 levels (P = 0.378). There were positive correlations between
      Vav3 with Rac-1 and MMP-7 in cancer tissues (P < 0.001), and also between Vav3
      and Rac-1 in pre-surgery blood (P = 0.003). CONCLUSIONS: Vav3 in peripheral blood
      may serve as a biomarker for gastric cancer, and to predict the lymphatic
      metastasis in gastric cancer.

PMID- 28513272
TI  - Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity
      and Gene Expression?
AB  - DNMT3A and 3B are the main de novo DNA methyltransferases (DNMTs) in the brain
      that introduce new methylation marks to non-methylated DNA in postmitotic
      neurons. DNA methylation is a key epigenetic mark that is known to regulate
      important cellular processes in neuronal development and brain plasticity.
      Accumulating evidence disclosed rapid and dynamic changes in DNA methylation of
      plasticity-relevant genes that are important for learning and memory formation.
      To understand how DNMTs contribute to brain function and how they are regulated
      by neuronal activity is a prerequisite for a deeper appreciation of activity
      dependent gene expression in health and disease. This review discusses the
      functional role of de novo methyltransferases and in particular DNMT3A1 in the
      adult brain with special emphasis on synaptic plasticity, memory formation, and
      brain disorders.

PMID- 28513275
TI  - Relationship Between Lower-Extremity Strength and Subjective Function in
      Individuals With Patellofemoral Pain.
AB  - OBJECTIVE: Evaluate the relationship between subjective knee function and lower
      extremity strength in individuals with patellofemoral pain (PFP). DESIGN: Cohort.
      SETTING: Laboratory. PARTICIPANTS: Participants were 30 individuals with PFP (20
      females and 10 males; 76.02 [17.88] kg, 173.04 [7.58] cm, and 24.9 [7] y). MAIN
      OUTCOME MEASURES: Subjects completed the Activities of Daily Living Scale (ADLS)
      and had lower-extremity hip and knee isometric strength assessed. Strength was
      compared between low and high subjective functioning ADLS groups. Correlations
      for strength and subjective function were assessed, with a linear regression
      utilized to determine if strength predicted subjective function. RESULTS:
      Quadriceps strength was significantly greater in the high subjective function
      group (38.5 [13.9] percent body mass) than in the low subjective function group
      (27.88 [8.96] percent body mass, P = .02). Significant correlations were seen
      between the ADLS and all 5 lower-extremity strength measures (r = .376-.535).
      Quadriceps strength was a strong predictor of subjective function in those with
      PFP, explaining 28.6% of the total variance in the ADLS. CONCLUSIONS: Quadriceps
      strength was a strong predictor of subjective function when assessed by the ADLS
      in patients with PFP and significantly greater in those with higher subjective
      function. A strong relationship exists between self-reported function and lower
      extremity strength, suggesting the need to evaluate and treat lower-extremity
      weakness.

PMID- 28513274
TI  - Cognitive functioning and adjudicative competence: defendants referred for
      neuropsychological evaluation in a psychiatric inpatient setting.
AB  - OBJECTIVE: A paucity of peer-reviewed research exists regarding the relation
      between cognitive functioning and adjudicative competence, despite increasing
      awareness of cognitive deficits associated with serious mental illness. This
      retrospective study sought to add to and expand upon existing research by
      considering performance validity and court determinations of competence, when
      available. METHOD: We compared demographic and cognitive variables of a group of
      defendants with presumed valid testing admitted to an inpatient psychiatric
      facility for evaluation of adjudicative competence and referred for
      neuropsychological evaluation (n = 45) and compared individuals determined by the
      evaluator and/or the court to be competent (n = 30) and incompetent (n = 15).
      RESULTS: Defendants who were incompetent were more likely to be diagnosed with a
      cognitive disorder, with a medium effect size. There was a difference in tests of
      immediate and delayed memory as measured by the Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS), with medium to large effects,
      and high delayed memory scores were helpful in ruling out incompetence (Negative
      predictive power = 85.71%). CONCLUSIONS: These results provide support for the
      relationship between cognitive functioning and trial competence, particularly at
      high and low levels of performance.

PMID- 28513276
TI  - Attachment avoidance, but not anxiety, minimizes the joys of caregiving.
AB  - Perhaps unlike other social roles that people may hold, caring for children
      offers opportunities for both immense joy and incredible frustration. Yet what
      predicts how parents will feel during caregiving experiences? In the current
      study, we examined parents' (N = 152) positive emotion, negative emotion, and
      felt meaning during caregiving using the Day Reconstruction Method. In addition,
      we tested attachment anxiety and avoidance as predictors of parents' emotion
      during caregiving relative to their other daily experiences. We found that
      attachment avoidance was associated with elevated negative emotion and reduced
      positive emotion and meaning in life across the entire day, whereas attachment
      anxiety was associated with elevated negative emotion and marginally greater
      meaning in life, but not positive emotion, across the entire day. Furthermore,
      caregiving was associated with greater positive emotion and meaning, but not
      negative emotion, compared to parents' other daily activities. Finally,
      attachment avoidance, but not anxiety, was associated with lower levels of
      positive emotion, negative emotion, and felt meaning during caregiving compared
      to other daily activities. These findings are consistent with other evidence that
      attachment avoidance is associated with deactivation of emotion in close
      relationships and suggest that attachment avoidance minimizes the joys of
      parenting.

PMID- 28513269
TI  - Immune surveillance in melanoma: From immune attack to melanoma escape and even
      counterattack.
AB  - Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the
      programmed death receptor-1 (PD1) has resulted in unprecedented durable responses
      in metastatic melanoma. However, resistance to immunotherapy remains a major
      challenge. Effective immune surveillance against melanoma requires 4 essential
      steps: activation of the T lymphocytes, homing of the activated T lymphocytes to
      the melanoma microenvironment, identification and episode of melanoma cells by
      activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis. At
      each of these steps, there are multiple factors that may interfere with the
      immune surveillance machinery, thus allowing melanoma cells to escape immune
      attack and develop resistance to immunotherapy. We provide a comprehensive review
      of the complex immune surveillance mechanisms at play in melanoma, and a detailed
      discussion of how these mechanisms may allow for the development of intrinsic or
      acquired resistance to immunotherapeutic modalities, and potential avenues for
      overcoming this resistance.

PMID- 28513277
TI  - Effect of Gastrocnemius Kinesio Taping on Countermovement Jump Performance and
      Vertical Stiffness Following Muscle Fatigue.
AB  - CONTEXT: Kinesio tape (KT) is a widely used intervention in the fields of sports
      and rehabilitation. However, its effects on lower-extremity behavior during
      functional activities are not entirely known. OBJECTIVE: To test the hypothesis
      that application of KT can change performance and vertical stiffness (VS) during
      the countermovement jump (CMJ) before and after a fatigue protocol. DESIGN: A
      predesign and postdesign to study the effect of KT in 2 situations, prefatigue
      and postfatigue. In each fatiguing condition, there were 2 conditions with and
      without KT application on the gastrocnemius muscle. SETTING: Biomechanics
      laboratory. PARTICIPANTS: Fifty healthy, nonathlete participants (26 females and
      24 males). INTERVENTIONS: KT application on the gastrocnemius muscle and a
      fatigue protocol to induce fatigue in plantar flexor muscles. MAIN OUTCOME
      MEASURES: Various jumping parameters, including jump height, maximum force,
      maximum power, rate of force development, eccentric lower-limb stiffness, and VS,
      were calculated using the vertical ground reaction force data. Eccentric lower
      limb stiffness and VS were calculated using a mass-spring model. The studied
      variables can present lower-extremity elastic behavior and performance during
      CMJ. RESULTS: The results of a 2-way repeated-measures analysis of variance
      showed no significant effect for KT application. Fatigue resulted in lower values
      of jump height, maximum power, and VS. Moreover, male subjects showed greater
      values of jump height, maximum force, and maximum power than did females.
      CONCLUSIONS: The main finding of this study was that gastrocnemius KT has no
      effect on performance or elastic behavior of the lower-extremity during CMJ.
      Moreover, KT cannot reduce the adverse effect of fatigue in a functional activity
      such as CMJ. It seems that gastrocnemius KT is not effective for demanding
      activities.

PMID- 28513278
TI  - Infraspinatus Isolation During External Rotation Exercise at Varying Degrees of
      Abduction.
AB  - CONTEXT: External rotation (ER) strengthening exercises are a common component of
      shoulder injury prevention and rehabilitation programs. They are primarily
      intended to target the infraspinatus muscle, based on its role in glenohumeral
      stabilization and inferior humeral glide. ER also recruits the posterior deltoid,
      which can be undesirable due to its role in subacromial space narrowing.
      OBJECTIVE: To determine the angle of humeral abduction that maximizes the
      infraspinatus to posterior deltoid activation ratio (INFRA/PD) during ER. DESIGN:
      Within-subjects repeated-measures controlled lab trial. PARTICIPANTS: A total of
      10 healthy participants (5 males, 5 females) aged 21 (0.67) years participated in
      the study. INTERVENTION: 7 consecutive repetitions of ER at 7 different abduction
      angles ranging from 0 degrees  to 90 degrees , with resistance normalized to 3%
      body mass. MAIN OUTCOME MEASURES: Surface electromyography was performed on the
      infraspinatus, middle deltoid, and posterior deltoid. Surface electromyography
      data were processed to determine absolute muscle activation as well as INFRA/PD
      at each abduction angle. Group means were compared between abduction angles using
      1-way analysis of variance. RESULTS: Abduction significantly reduced overall
      infraspinatus activity but increased posterior deltoid activity (P < .01).
      Average and peak INFRA/PD decreased as the angle of abduction increased (P < .001
      and P < .01, respectively). CONCLUSION: Our findings suggest that ER should be
      performed in 0 degrees  of abduction to maximize infraspinatus isolation. Slight
      abduction, such as placing a towel under the humerus, as recommended by some
      clinicians, may improve patient comfort, but did not increase infraspinatus
      isolation in this study.

PMID- 28513280
TI  - Application of Acoustic Radiation Force Impulse Elastography in Imaging of
      Delayed Onset Muscle Soreness: A Comparative Analysis With 3T MRI.
AB  - CONTEXT: Delayed onset muscle soreness is one of the most common reasons for
      impaired muscle performance in sports and is associated with reduced muscle
      strength and frequently observed both in professional and recreational athletes.
      OBJECTIVE: To emphasize the diagnostic value of acoustic radiation force impulse
      (ARFI) in imaging of delayed onset muscle soreness by comparing findings with
      high-resolution 3T magnetic resonance imaging T2-weighted sequences. DESIGN: Case
      series. SETTING: Laboratory environment. PARTICIPANTS: Fifteen healthy students
      (7 females and 8 males; mean [SD]: age 24 [4] y, height 178 [10] cm, body weight
      67 [12] kg). MAIN OUTCOME MEASURES: ARFI values, represented as shear wave
      velocities of the gastrocnemius muscle and soleus muscle, as well as conventional
      ultrasound, high-resolution 3T magnetic resonance imaging, creatine kinase
      activity, extension range of the ankle joint, calf circumference, and muscle
      soreness were assessed before (baseline) and 60 hours after (postintervention) a
      standardized eccentric exercise. RESULTS: ARFI shear wave velocity values of the
      gastrocnemius muscle revealed a statistically significant decrease of 19.1%
      between baseline (2.2 [0.26] m/s) and postintervention (1.78 [0.24] m/s); P =
      .01. At follow-up, the magnetic resonance imaging investigations showed
      intramuscular edema for the gastrocnemius muscle in all participants
      corresponding to a significant raise in T2 signal intensity (P = .001) and in T2
      time values (P = .004). CONCLUSIONS: ARFI elastography seems to be an additional
      sensitive diagnostic modality in the diagnostic workup of delayed onset muscle
      soreness. Intramuscular shear wave velocities could represent an additional
      imaging marker for the assessment and monitoring of ultrastructural muscle
      injuries and therefore be helpful for individual training composition in elite
      sports.

PMID- 28513281
TI  - Short-Term Effects of Kinesio Taping on Muscle Recruitment Order During a
      Vertical Jump: A Pilot Study.
AB  - CONTEXT: Kinesio taping is commonly used in sports and rehabilitation settings
      with the aim of prevention and treatment of musculoskeletal injuries. However,
      limited evidence exists regarding the effects of 24 and 72 hours of kinesio
      taping on trunk and lower limb neuromuscular and kinetic performance during a
      vertical jump. OBJECTIVE: The purpose of this study was to analyze the short-term
      effects of kinesio taping on height and ground reaction force during a vertical
      jump, in addition to trunk and lower limb muscle latency and recruitment order.
      DESIGN: Single-group pretest-posttest. SETTING: University laboratory.
      PARTICIPANTS: Twelve male athletes from different sports (track and field,
      basketball, and soccer). INTERVENTIONS: They completed a single squat and
      countermovement jump at basal time (no kinesio taping), 24, and 72 hours of
      kinesio taping application on the gluteus maximus, biceps femoris, rectus
      femoris, gastrocnemius medialis, and longissimus. MAIN OUTCOME MEASURES: Muscle
      onset latencies were assessed by electromyography during a squat and
      countermovement jump, in addition to measurements of the jump height and
      normalized ground reaction force. RESULTS: The kinesio taping had no effect after
      24 hours on either the countermovement or squat jump. However, at 72 hours, the
      kinesio taping increased the jump height (P = .02; d = 0.36) and normalized
      ground reaction force (P = .001; d = 0.45) during the countermovement jump. In
      addition, 72-hour kinesio taping reduced longissimus onset latency (P = .03; d =
      1.34) and improved muscle recruitment order during a countermovement jump.
      CONCLUSIONS: These findings suggest that kinesio taping may improve neuromuscular
      and kinetic performance during a countermovement jump only after 72 hours of
      application on healthy and uninjured male athletes. However, no changes were
      observed on a squat jump. Future studies should incorporate a control group to
      verify kinesio taping's effects and its influence on injured athletes.

PMID- 28513279
TI  - w09, a novel autophagy enhancer, induces autophagy-dependent cell apoptosis via
      activation of the EGFR-mediated RAS-RAF1-MAP2K-MAPK1/3 pathway.
AB  - The EGFR (epidermal growth factor receptor) signaling pathway is frequently
      deregulated in many malignancies. Therefore, targeting the EGFR pathway is
      regarded as a promising strategy for anticancer drug discovery. Herein, we
      identified a 2-amino-nicotinonitrile compound (w09) as a novel autophagy
      enhancer, which potently induced macroautophagy/autophagy and consequent
      apoptosis in gastric cancer cells. Mechanistic studies revealed that EGFR
      mediated activation of the RAS-RAF1-MAP2K-MAPK1/3 signaling pathway played a
      critical role in w09-induced autophagy and apoptosis of gastric cancer cells.
      Inhibition of the MAPK1/3 pathway with U0126 or blockade of autophagy by specific
      chemical inhibitors markedly attenuated the effect of w09-mediated growth
      inhibition and caspase-dependent apoptosis. Furthermore, these conclusions were
      supported by knockdown of ATG5 or knockout of ATG5 and/or ATG7. Notably, w09
      increased the expression of SQSTM1 by transcription, and knockout of SQSTM1 or
      deleting the LC3-interaction region domain of SQSTM1, significantly inhibited w09
      induced PARP1 cleavage, suggesting the central role played by SQSTM1 in w09
      induced apoptosis. In addition, in vivo administration of w09 effectively
      inhibited tumor growth of SGC-7901 xenografts. Hence, our findings not only
      suggested that activation of the EGFR-RAS-RAF1-MAP2K-MAPK1/3 signaling pathway
      may play a critical role in w09-induced autophagy and apoptosis, but also imply
      that induction of autophagic cancer cell death through activation of the EGFR
      pathway may be a potential therapeutic strategy for EGFR-disregulated gastric
      tumors.

PMID- 28513282
TI  - Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid
      metabolism in the streptozotocin-induced diabetic rats.
AB  - This study aimed to evaluate the effects of Zanthoxylum alkylamides on the
      glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes.
      Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides
      for 28 days. Alkylamides significantly decreased fasting blood glucose and
      fructosamine content, as well as relieved organ enlargement caused by diabetes.
      The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents
      of rats with STZ-induced diabetes were significantly reduced. Total cholesterol
      in the liver also significantly decreased. Quantitative polymerase chain reaction
      (Q-PCR) and Western blot detected insignificantly increased (P > 0.05) mRNA
      expression levels of adenosine monophosphate-activated protein kinase (AMPK) in
      the skeletal muscle of diabetic rats. However, AMPK and p-AMPK (Thr172) protein
      expression levels significantly increased. The mRNA and protein expression levels
      of silencing information regulator 1 significantly increased. The mRNA expression
      levels of acetyl-CoA-carboxylase (ACC) and protein p-ACC (Ser79) also increased.
      The mRNA and protein expression levels of glucose transporter type 4 (GLUT4) were
      significantly upregulated in the skeletal muscle cell membranes of diabetic rats.
      Results indicated that alkylamides activated the AMPK-signaling pathway. Thus,
      inhibiting ACC activity reduced fatty-acid synthesis. The rapid translocation of
      GLUT4 mediated increased glucose transport rate and reduced blood glucose.
      Therefore, alkylamides can ameliorate glucose and lipid metabolism disorders in
      diabetic rats by activating the AMPK pathway.

PMID- 28513284
TI  - Best Practices for Population Genetic Analyses.
AB  - Population genetic analysis is a powerful tool to understand how pathogens emerge
      and adapt. However, determining the genetic structure of populations requires
      complex knowledge on a range of subtle skills that are often not explicitly
      stated in book chapters or review articles on population genetics. What is a good
      sampling strategy? How many isolates should I sample? How do I include positive
      and negative controls in my molecular assays? What marker system should I use?
      This review will attempt to address many of these practical questions that are
      often not readily answered from reading books or reviews on the topic, but emerge
      from discussions with colleagues and from practical experience. A further
      complication for microbial or pathogen populations is the frequent observation of
      clonality or partial clonality. Clonality invariably makes analyses of population
      data difficult because many assumptions underlying the theory from which analysis
      methods were derived are often violated. This review provides practical guidance
      on how to navigate through the complex web of data analyses of pathogens that may
      violate typical population genetics assumptions. We also provide resources and
      examples for analysis in the R programming environment.

PMID- 28513283
TI  - Molecular Characterization of Australian Isolates of Puccinia graminis f. sp.
      tritici Supports Long-Term Clonality but also Reveals Cryptic Genetic Variation.
AB  - Long-term surveys of pathogenicity in Puccinia graminis f. sp. tritici in
      Australia have implicated mutation as a major source of virulence, at times
      leading to the demise of stem-rust-resistant wheat cultivars and substantial
      yield losses. Since 1925, these surveys have identified at least four occasions
      on which exotic isolates of P. graminis f. sp. tritici appeared in Australia,
      with each acting as a founding isolate that gave rise sequentially to derivative
      pathotypes via presumed single-step mutation. The current study examined the
      relationship between virulence and molecular patterns using simple-sequence
      repeat (SSR) markers on selected isolates of P. graminis f. sp. tritici collected
      in Australia during a 52-year period in order to propose an evolutionary pathway
      involving these isolates. Studies of SSR variability among this collection of
      isolates within a putative clonal lineage based on pathotype 21-0, first detected
      in 1954 (the "21/34 lineage"), provided compelling evidence of clonality over the
      52-year period, coupled with single-step acquisition of virulence for resistance
      genes. It also supported the postulation that two triticale-attacking pathotypes
      (34-2,12 and 34-2,12,13) detected in the early 1980s were derived from pathotype
      21-0 via stepwise sequential acquisition of virulence for Sr5, Sr11, Sr27, and
      then SrSatu. Some of the isolates examined that were regarded as members of the
      race 21/34 lineage based on pathogenicity differed significantly in their SSR
      genotypes, indicating that they may have originated from processes more complex
      than simple mutation. This included two isolates of pathotype 21-0, which were
      collected in 1994 and 2006. Given that sexual recombination in P. graminis is
      rare or absent in Australia, the cryptic complexity observed could indicate that
      one or more of these isolates arose as a consequence of asexual recombination.

PMID- 28513286
TI  - Azelnidipine is a useful medication for the treatment of heart failure preserved
      ejection fraction.
AB  - BACKGROUND: The optimal therapy in patients with heart failure preserved ejection
      fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker
      (BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are
      recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB),
      a major anti-hypertensive drugs in Japan, is also recommend as class IIa in
      patients with HFpEF. However, the difference between azelnidipine, an L type CCB,
      and cilnidipine, an N type CCB, is unclear. We investigated the difference
      between azelnidipine and cilnidipine in patients with HFpEF and HT. METHODS:
      Twenty-five consecutive HFpEF patients treated with BB and RAAS-I from April 2013
      to March 2015 were enrolled. Initially, cilnidipine was used, and then switched
      to azelnidipine. Age, gender, blood pressure (BP), heart rate (HR), blood tests,
      echocardiography, and cardiac-scintigraphy (123I-metaiodobenzylguanidine: MIBG)
      were measured before and after six months from azelnidipine administration.
      RESULTS: There was no statistically significant difference in BP. B type
      natriuretic peptides were significantly reduced (pre-state: 195.4 +/- 209.7 pg/ml
      and post-state: 140.7 +/- 136.4 pg/ml, p = 0.050). In echocardiography, the TEI
      index tended to be decreased (pre-state: 0.47 +/- 0.15 and post-state: 0.42 +/-
      0.08, p = 0.057). As for MIBG, there was no significant change in the
      heart/mediastinum ratio. However, the washout rate was significantly reduced (pre
      state: 44.7 +/- 12.2 and post-state: 40.7 +/- 12.1, p = 0.011). In addition,
      there was no statistically significant change, although HR tended to decrease by
      switching to azelnidipine (pre-state: 62.7 +/- 11.6 and post-state: 61.8 +/-
      16.5, p = 0.373). CONCLUSIONS: In patients with HT and HFpEF, azelnidipine
      improved the severity of HF and cardiac sympathetic nerve activity compared with
      cilnidipine.

PMID- 28513285
TI  - Hypertensive disorders of pregnancy increase the risk for chronic kidney disease:
      A population-based retrospective study.
AB  - Hypertensive disorders of pregnancy (HDP) and chronic kidney disease (CKD) are
      well-known risk factors for cardiovascular disease (CVD) in later life. However,
      few studies have investigated the association of HDP with CKD. Moreover, these
      studies utilized either registry- or clinical-based data and did not include
      subclinical CKD patients. To address this gap in the literature, we investigated
      whether HDP is related to CKD, diagnosed based on the estimated glomerular
      filtration rate (eGFR), in later life. We designed a population-based,
      retrospective study, and reviewed the results of blood and physiological
      examinations as well as the results of pregnancy data available in patients'
      Maternity Health Record Books for 312 women. We identified 15 women with a
      diagnosis of CKD based on the eGFR, and 14 women with HDP. We found that women
      who experienced HDP had a high risk of CKD in later life compared with women
      without HDP (odds ratio (OR): 4.854; 95% confidence interval (CI): 1.042-22.621).
      Compared with normotensive women, those who were hypertensive at the time of the
      examination were significantly associated with CKD (OR: 3.109; 95% CI: 1.213
      11.510). Awareness regarding the risk for CKD and CVD in a relatively young age
      can enable women to prevent diseases effectively.

PMID- 28513287
TI  - Contact force technology integrated with 3D navigation system for atrial
      fibrillation ablation: improving results?
AB  - INTRODUCTION: Pulmonary veins isolation (PVI) by radiofrequency (RF) ablation is
      currently an established treatment for symptomatic, drug-resistant paroxysmal
      atrial fibrillation. Although the effectiveness of the therapy has been clearly
      demonstrated, success rate after a single procedure is still sub-optimal. The
      main reason for recurrences after PVI is electrical pulmonary vein-atrium
      reconnection. In order to increase the likelihood of permanent PVI, the creation
      of a transmural, durable lesion is mandatory. The main determinants of lesion
      size and transmurality are power, stability, duration and contact-force during RF
      application. In recent times, catheters with contact-force sensors have been
      developed and released for clinical use. Areas covered: The present review
      summarizes rational and clinical evidences for efficacy and safety of contact
      force (CF) technology integrated into 3D navigation systems for AF ablation.
      Expert commentary Although CF technology has a strong rational, clinical data on
      the superior safety and efficacy of CF technology over traditional non-CF
      catheters are still conflicting. The reason for that is very likely to rely on
      the lack of definite data on how to optimize CF parameters and how to integrate
      CF data with power, duration of RF applications and information on catheter
      stability.

PMID- 28513288
TI  - Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early
      detection of diabetic nephropathy.
AB  - BACKGROUND: To investigate the diagnostic level of cystatin C and growth arrest
      specific gene 6 (Gas6) levels in elderly type 2 diabetic patients with different
      degrees of diabetic nephropathy (DN). METHODS: Four hundred and eighty-two old
      people, including 130 healthy controls, 130 normoalbuminuric diabetic patients,
      122 with microalbuminuria, and 100 with macroalbuminuria, were recruited. Plasma
      Gas6 and serum cystatin C levels were measured. RESULTS: Plasma Gas6
      concentration was significantly lower in diabetic patients with microalbuminuria
      or macroalbuminuria, as compared with diabetic subjects with normoalbuminuria;
      while cystatin C was significantly higher. Gas6 was inversely correlated with
      BMI, WHR, and HbA1c, while cystatin C was inversely correlated with urea nitrogen
      and creatinine. Multivariate logistic regression analysis showed that, after
      adjusted for established diabetes risk factors, higher plasma Gas6 was
      significantly associated with a decreased risk of DN, while higher serum cystatin
      C was significantly associated with an increased risk. Receiver operating
      characteristic curve analysis showed that Gas6 was better than cystatin C as a
      biomarker for early diagnosis and detection of DN, with a cutoff value of 9.435
      ng/mL (86.1% sensitivity and 84.6% specificity). CONCLUSION: Compared to cystatin
      C, Gas6 may be potentially a better noninvasive diagnostic biomarker for early
      detection of DN.

PMID- 28513289
TI  - Detection of meat species adulteration using high-resolution mass spectrometry
      and a proteogenomics strategy.
AB  - Due to the internationalisation of food production and distribution, there has
      been a significant increase of food fraud in recent years. Food fraud can have
      serious health implications, and it occurs when food manufacturers implement
      unethical practices such as making false label claims as well as using additives
      and fillers within their products to increase profitability. This has been a
      serious concern. Meat adulteration was examined using a well-defined
      proteogenomic annotation, carefully selected surrogate tryptic peptides and high
      resolution mass spectrometry. Selected mammalian meat samples were homogenised
      and the proteins extracted and digested with trypsin. Chromatography was achieved
      using a 30-min linear gradient along with a BioBasic C8 100 * 1 mm column at a
      flow rate of 75 ul min-1. The mass spectrometer was operated in full-scan high
      resolution and accurate mass using resolving powers of 140,000 and 17,500 (FWHM)
      in full-scan MS and MS/MS respectively. Data independent acquisition (DIA) mode
      was used including 12 DIA MS/MS scans to cover the mass range 600-1200 m/z.
      Methodically in silico analyses of myoglobin, myosin-1, myosin-2 and beta
      haemoglobin sequences allow for the identification of a species-specific tryptic
      peptide mass lists and theoretical MS/MS spectra. Following comprehensive MS,
      MS/MS or DIA analyses, the method was capable of the detection and identification
      of very specific tryptic peptides for all four targeted proteins for each animal
      species tested with observed m/z below 3 ppm compared with the theoretical m/z.
      The analyses were successfully performed with raw and cooked meat. Specifically,
      the method was capable of detecting 1% (w/w) of pork or horse meat in a mixture
      before and after cooking (71 degrees C internal temperature).

PMID- 28513290
TI  - Examining the relationship between encouragement and health-related quality of
      life among Muslims.
AB  - This study examines the relationship between encouragement and health-related
      quality of life (HRQOL) among a sample of American Muslims, in tandem with the
      potential mediating effects of depression and spirituality. To conduct this cross
      sectional study, a model was developed and tested using structural equation
      modeling (SEM) with a community sample of Muslims (N = 284). The results indicate
      that encouragement has a direct, positive effect on HRQOL. Neither depression nor
      spirituality mediated the relationship between encouragement and HRQOL. Rather,
      both variables exhibited a direct, independent effect on HRQOL. In addition,
      spirituality exhibited an indirect effect on HRQOL through attenuating
      depression. The findings underscore the importance of encouragement as a pathway
      to enhance HRQOL among Muslims in post-9/11 America. The results also suggest
      that spirituality can play a significant role in fostering HRQOL among Muslims,
      both directly and indirectly by reducing the effects of depression on HRQOL.

PMID- 28513291
TI  - Low-cost mobile air pollution monitoring in urban environments: a pilot study in
      Lubbock, Texas.
AB  - The complex nature of air pollution in urban areas prevents traditional
      monitoring techniques from obtaining measurements representative of true human
      exposure. The current study assessed the capability of low-cost mobile monitors
      to acquire useful data in a city without a monitoring network in place (Lubbock,
      Texas) using a bicycle platform. The monitoring campaign resulted in 30 days of
      data along a 13.4 km fixed concentric route. Due to high sensitivities to
      airflow, the apparent wind velocity was accounted for throughout the route. The
      data were also normalized into percentiles in order to visualize spatial
      patterns. The highest estimated pollution levels were located near frequently
      busy intersections and roads; however, sensor issues resulted in lower
      confidence. Additional research is needed concerning the appropriate use of low
      cost metal oxide sensors for citizen science applications, as measurements can be
      misleading if the user is unaware of sensors specifications. The simultaneous use
      of several low-cost mobile platforms, rather than a single platform, as well as
      the use of high-end cases, are recommended to create a more robust spatial
      analysis. The issues addressed from this research are important to understand for
      accurate and beneficial application of low-cost gaseous monitors for citizen
      science.

PMID- 28513292
TI  - Analysis of cutting-oil emulsion destabilization by aluminum sulfate.
AB  - The destabilization mechanism of the high stable cutting-oil emulsion by aluminum
      sulfate (Al2(SO4)3) was investigated since it can affect properties of aggregates
      and following separation units. Al2(SO4)3 dosage and pH were key factors in the
      destabilization. The effective separation occurred when precipitated Al(OH)3 is
      dominated at the neutral pH of 6.5-7.0. The best separation can be achieved when
      solid flocs were formed at 1.0 mM, which exceeded the dosage from the critical
      coagulation concentration (CCC) of 0.75 mM. Two different mechanisms were proved
      for the emulsion destabilization depending upon the Al3+ concentration under this
      pH range. The first mechanism was the adsorption of Al(OH)3 on surface of oil
      droplets, which led to the droplet coalescence. By increasing the Al3+ dosage,
      the sweep flocculation by Al(OH)3 precipitates occurred. Al3+ dosage for
      effective destabilization was increased in accordance with oil concentration. The
      formation of aluminum hydroxide precipitates in bayerite structure was affirmed
      by analyzing elemental composition and crystalline structure of flocs from the
      destablization.

PMID- 28513293
TI  - Effect of organic matter on mobilization of antimony from nanocrystalline
      titanium dioxide.
AB  - Antimony (Sb) is of increasing environmental concern worldwide. The sorption
      behavior of Sb was investigated. Both Sb(III) and Sb(V) were likely to be sorbed
      onto nanocrystalline titanium dioxide (TiO2). Sorption studies showed that the
      Sb(V) sorption capacity and rate for TiO2 were greater than those of Sb(III). The
      highest Sb(III) and Sb(V) sorption on TiO2, on the basis of the Langmuir
      equation, were 333 and 588 mmol kg-1, respectively. The study suggested that TiO2
      is an effective adsorbent for Sb removal. In addition, Sb mobilization in the
      presence of humic acid (HA) was found to be highly pH-dependent. For pH values of
      9-11, the addition of HA enhanced Sb mobilization significantly. The results
      highlight the importance of organic matter in the mobilization of Sb in alkaline
      contaminated environments.

PMID- 28513294
TI  - Efficacy of propidium iodide and FUN-1 stains for assessing viability in
      basidiospores of Rhizopogon roseolus.
AB  - The use of spores in applications of ectomycorrhizal fungi requires information
      regarding spore viability and germination, especially in genera such as
      Rhizopogon with high rates of spore dormancy. The authors developed a protocol to
      assess spore viability of Rhizopogon roseolus using four vital stains to quantify
      spore viability and germination and to optimize storage procedures. They showed
      that propidium iodide is an excellent stain for quantifying nonviable spores.
      Observing red fluorescent intravacuolar structures following staining with 2
      chloro-4-(2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene)-1
      phenylquinolinium iodide (FUN-1) can help identify viable spores that are
      activated. At 6 mo and 1 y, the spores kept in a water suspension survived better
      than those left within intact, dry gasterocarps. Our work highlights the
      importance of temperature, nutrients, and vitamins for maturation and germination
      of spores of R. roseolus during 1 y of storage.

PMID- 28513296
TI  - Confirmatory biopsy of men under active surveillance: extended versus saturation
      versus multiparametric magnetic resonance imaging/transrectal ultrasound fusion
      prostate biopsy.
AB  - OBJECTIVE: The aim of this study was to evaluate the detection rate for
      clinically significant prostate cancer (PCa) after multiparametric magnetic
      resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion biopsy versus
      extended biopsy or saturation prostate biopsy (SPBx) in men enrolled on active
      surveillance (AS). MATERIALS AND METHODS: From May 2013 to January 2016, 100 men
      with very low-risk PCa were enrolled on AS. Eligible criteria were: life
      expectancy greater than 10 years, cT1c, prostate-specific antigen (PSA) below 10
      ng/ml, PSA density less than 0.20 ng/ml2, three or fewer unilateral positive
      biopsy cores, Gleason score (GS) equal to 6 and greatest percentage of cancer in
      a core 50% or lower. All patients underwent 3.0 T pelvic mpMRI before
      confirmatory transperineal extended biopsy (20 cores) and SPBx (median 30 cores)
      combined with mpMRI/TRUS fusion targeted biopsy (median four cores) of suspicious
      lesions [Prostate Imaging Reporting and Data System (PI-RADS) 3-5]. Clinically
      significant PCa was defined as the presence of at least one core with a GS of 4
      or higher. RESULTS: After confirmatory biopsy, 16 out of 60 (26.6%) patients
      showed significant PCa. Targeted biopsy of PI-RADS 4-5 versus PI-RADS 3-5 lesions
      diagnosed six out of 16 (37.5%) and 12 out of 16 (87.5%) significant PCa,
      respectively, with two false positives (5%). The detection rate for significant
      PCa was equal to 68.8% on mpMRI/TRUS fusion biopsy, 75% on extended biopsy and
      100% on SPBx. mpMRI/TRUS targeted biopsy and extended biopsy missed five out of
      16 (31.2%) and four out of 16 (25%) PCa, respectively. CONCLUSIONS: Although
      mpMRI may improve the diagnosis of significant PCa in men under AS, SPBx had a
      higher detection rate for clinically significant PCa.

PMID- 28513298
TI  - Cleaning of lead smelting flue gas scrubber sludge and recovery of lead, selenium
      and mercury by the hydrometallurgical route.
AB  - The expansion of the nonferrous metal smelting industry in the recent two decades
      has resulted in the generation of massive quantities of flue gas scrubber sludge
      containing hazardous heavy metals, such as cadmium, lead, arsenic, selenium and
      mercury (Hg), posing a potential environmental threat. In this work, lead
      smelting flue gas scrubber sludge was treated by a hydrometallurgical process to
      achieve sludge cleaning and economic recovery of metal values lead, selenium and
      mercury. The sludge was preliminarily leached by sodium chloride solution to
      extract lead. Under the optimum conditions, 99.8% of lead was selectively leached
      into the solution and subsequently precipitated by calcium oxide while almost the
      entire selenium and mercury remained in residue. Ninety-eight percent of selenium
      and 99.8% of mercury were further leached by hydrochloric acid solution with
      sodium chlorate. 99.3% of mercury was precipitated as red mercuric oxide from the
      Se-Hg leach liquor by adding sodium hydroxide. After the mercury was removed from
      the solution, 97.5% of selenium was reduced and precipitated as crude selenium by
      reduction with sodium sulfite. Recovery yields of lead, mercury and selenium by
      this process were 99.6%, 98.9% and 95.5%, respectively.

PMID- 28513297
TI  - Former food products safety: microbiological quality and computer vision
      evaluation of packaging remnants contamination.
AB  - The use of alternative feed ingredients in farm animal's diets can be an
      interesting choice from several standpoints, including safety. In this respect,
      this study investigated the safety features of selected former food products
      (FFPs) intended for animal nutrition produced in the framework of the IZS PLV
      06/14 RC project by an FFP processing plant. Six FFP samples, both mash and
      pelleted, were analysed for the enumeration of total viable count (TVC) (ISO
      4833), Enterobacteriaceae (ISO 21528-1), Escherichia coli (ISO 16649-1),
      coagulase-positive Staphylococci (CPS) (ISO 6888), presumptive Bacillus cereus
      and its spores (ISO 7932), sulphite-reducing Clostridia (ISO 7937), yeasts and
      moulds (ISO 21527-1), and the presence in 25 g of Salmonella spp. (ISO 6579). On
      the same samples, the presence of undesired ingredients, which can be identified
      as remnants of packaging materials, was evaluated by two different methods:
      stereomicroscopy according to published methods; and stereomicroscopy coupled
      with a computer vision system (IRIS Visual Analyzer VA400). All FFPs analysed
      were safe from a microbiological point of view. TVC was limited and Salmonella
      was always absent. When remnants of packaging materials were considered, the
      contamination level was below 0.08% (w/w). Of note, packaging remnants were found
      mainly from the 1-mm sieve mesh fractions. Finally, the innovative computer
      vision system demonstrated the possibility of rapid detection for the presence of
      packaging remnants in FFPs when combined with a stereomicroscope. In conclusion,
      the FFPs analysed in the present study can be considered safe, even though some
      improvements in FFP processing in the feeding plant can be useful in further
      reducing their microbial loads and impurity.

PMID- 28513299
TI  - Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced
      by andrographolide via upregulation of phospho-p53 in vitro and in vivo.
AB  - Oral squamous cell carcinoma is one of the most common neoplasm in the world.
      Despite the improvements in diagnosis and treatment, the outcome is still poor
      now. Thus, the development of novel therapeuticapproaches is needed. The aim of
      this study is to assess the synergistic anti-tumor effect of andrographolide with
      cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in
      vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and
      western blotting on CAL-27 cells treated with andrographolide, DDP or the
      combination in vitro. In vivo, we also treated CAL-27 xenografts with
      andrographolide or the combination, and performed terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling assay and
      immunohistochemical analysis of Ki-67. The results showed the combination of
      andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in
      vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition,
      the synergistic anti-tumor effect of andrographolide with synergistic was due to
      an enhanced apoptosis. Moreover, the combination therapy upregulated the
      expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our
      data indicate that the combination treatment of andrographolide and DDP results
      in synergistic anti-tumor growth activity against oral squamous cell carcinoma
      CAL-27 in vitro and in vivo. These results demonstrated that combination of
      andrographolide with DDP was likely to represent a potential therapeutic strategy
      for oral squamous cell carcinoma.

PMID- 28513301
TI  - Modern strategies and capabilities for activation of the immune response against
      tumor cells.
AB  - Dendritic cells are professional antigen-presenting cells and the most potent
      stimulators of various immune responses, such as antitumor responses. Modern
      studies have not shown an effective antitumor immune response development in
      patients with malignant tumors. The major cause is the decrease in functional
      activity of dendritic cells in cancer patients through irregularities in the
      maturation process to a functionally active form and in the antigen presentation
      process to naive T lymphocytes. This review describes the main stages of cellular
      antitumor immune response induction in vitro, aimed at resolving the problems
      that are blocking the full functioning of dendritic cells, and additional
      stimulation of antitumor immune response.

PMID- 28513300
TI  - S100A11 regulates renal carcinoma cell proliferation, invasion, and migration via
      the EGFR/Akt signaling pathway and E-cadherin.
AB  - S100A11 is a S100 protein family member that contributes to cancer progression.
      Upregulated in human renal cancer tissues, S100A11 may be a prognostic marker for
      clear cell renal cell carcinoma, but how it functions in cancer is uncertain.
      Thus, we studied S100A11 and noted knockdown of S100A11 using short hairpin RNA,
      which inhibited proliferation, invasion, and migration of renal carcinoma cells
      as well as increased expression of E-cadherin and decreased expression of
      epidermal growth factor receptor/Akt in renal carcinoma cells. Therefore, S100A11
      may be a key molecular target for treating renal carcinoma.

PMID- 28513302
TI  - Controlled release of 1-methylcyclopropene from its functionalised electrospun
      fibres under constant and linearly ramped humidity.
AB  - The methodology to electrospin polystyrene (PS) fibres functionalised with the
      inclusion complex between 1-methylcyclopropene (1-MCP) and alpha-cyclodextrin
      (alpha-CD) has been developed successfully. Due to limited availability, alpha-CD
      crystals instead of 1-MCP/alpha-CD complex were suspended in the electrospinning
      (ES) solutions to investigate the ES process. The ES solutions were characterised
      in terms of viscosity, conductivity and surface tension. Meanwhile, the fibres
      were subjected to scanning electron microscopy. The average fibre diameter was
      proportional to approximately one-sixth power of the capillary number of the ES
      solution. Viscosity, which was a function of PS concentration and alpha-CD
      loading, was the main property that dictated the spin ability of the ES
      solutions. ES fibres with 1.5-4.4 MUm in diameter were produced with 12.5-20.0%
      (w/w) PS in ES solution and an equal amount of the inclusion complex for PS. In
      the case of the ES solutions of 20 wt% PS loaded with the inclusion complex from
      0 to 100% (w/w) to PS, all the ES solutions were electrospinnable with the
      average diameter ranging from 3.8 to 4.6 MUm. X-ray diffractometry indicated that
      the alpha-CD crystals were homogeneously suspended on the fibre mats. Confocal
      laser scanning microscopy showed that the crystals were suspended on the fibre
      mats while being coated with a layer of PS. The complex-functionalised fibre was
      formed from the ES solution of 20% PS and 50% (w/w) inclusion complex with the
      ES. The release characteristics of 1-methylcyclopropene (1-MCP) from the
      functionalised fibre and the inclusion complex were investigated real time under
      linearly ramping humidity conditions at constant temperatures with a home-built
      humidity regulating system coupled with gas chromatography. The irregular release
      profiles were successfully modelled and the activation energies of release for
      the functionalised fibre and inclusion complex were about 128 and 69 kJ/mol,
      respectively..

PMID- 28513303
TI  - Effects of Functional-Task Training on Older Adults With Alzheimer's Disease.
AB  - The aim of this study was to verify the effects of functional-task training on
      cognitive function, activities of daily living (ADL) performance, and functional
      fitness in community-dwelling older adults with diagnosis of Alzheimer's disease
      (AD). A total of 57 participants (22 functional-task training group [FTG], 21
      social gathering group [SGG], 14 control group [CG]) were recruited. Participants
      in both intervention groups carried out three 1-hr sessions per week of a
      functional-task program and social gathering activities for 12 weeks. Significant
      improvements were observed in executive functions (TMT, t-test, p = .03) in the
      SGG and in upper limb strength (arm curl, t-test, p = .01) in the FTG. Functional
      task training has no significant effect on cognitive function, ADL, and
      functional fitness among people with AD, although it may contribute to slowing
      down the process of deterioration this illness causes.

PMID- 28513304
TI  - Using a sedimentation scanner to determine mangrove health responses to
      sedimentation derived from dredging. An example from northwestern Australia.
AB  - A sedimentation scanner was used to measure daily sediment height at 10 sites
      associated with a 14 million cubic metre dredging project in Port Hedland
      harbour, Western Australia, between July 2011 and May 2012. Data were collected
      from seven potential impact sites, where up to 35 mm of additional sedimentation
      was predicted via modelling to result from dredging and at three reference sites,
      where background variation was monitored. A variety of mangrove habitat health
      indices from each site (including leaf area and health, pneumatophore and faunal
      burrow density) were collected before, during and after dredging. Despite
      predictions, most impact sites received between 0 and 10 mm over the dredging
      period, with one site experiencing a gain of 28 mm. Reference sites received
      between 2 and 28 mm which was attributed to natural processes. It was concluded
      that the health of Avicennia marina (Forssk.) Vierh. and Rhizophora stylosa
      Griff., the most common mangroves, were neither affected by a net sedimentation
      up to 28 mm of over a period of 11 months (i.e. 30.5 mm y-1) nor rapid changes
      over shorter time periods such as 14 mm over two days. This technology could be
      deployed in any tidally influenced sedimentary environment where short-term
      processes were of interest.

PMID- 28513307
TI  - Foundation for Veterinary Dentistry: Veterinary Dental Research Grant.

PMID- 28513311
TI  - Scholarship Application.

PMID- 28513305
TI  - Do Sitting, Standing, or Treadmill Desks Impact Psychobiological Indicators of
      Work Productivity?
AB  - BACKGROUND: This pilot study investigated the links between psychobiological
      indicators of work productivity, prolonged desk sitting, and conditions whereby
      office workers were able to interrupt sitting using a sit-stand or treadmill
      desk. METHODS: Twenty participants visited our laboratory and completed their own
      desk work in counterbalanced sit-only, sit-stand (Varidesk Pro Plus 48TM), and
      sit-walk conditions (Infiniti TR1200-DTSTM). Steady-state visually evoked
      potentials calculated from electroencephalography recordings during a set task at
      the end of the workday assessed attentional resource. Salivary cortisol samples
      were taken during the morning and afternoon to measure stress response. Within
      subject analyses were used to compare work productivity indicators relative to
      condition. RESULTS: No significant differences in mean steady-state visually
      evoked potential amplitude were observed, although attentional resource
      allocation was found to be the most effective following the sit-stand [1.01
      (0.46) MUV] compared with the sit-walk [0.9 (0.28) MUV] and sit-only [0.91 (0.32)
      MUV] conditions. The mean magnitude of decrease in cortisol was most apparent
      when workers used treadmill (1.5 nmol/L; P = .007) and sit-stand (1.6 nmol/L; P =
      .001) desks, and least evident in the sit-only condition (1.0 nmol/L; P = .146).
      CONCLUSIONS: The findings highlight the potential benefits of standing or active
      deskwork to the allocation of attentional resources and the regulation of stress.

PMID- 28513312
TI  - Employment Opportunities.

PMID- 28513313
TI  - Odontogenic Fibromyxoma in a Cat: First Confirmed Case in This Species.
AB  - An inflammatory gingival mass surrounding resorbing teeth was diagnosed via
      biopsy in a 9-year-old domestic shorthair cat. A dorsal rim excision was
      performed to remove the entire mass with associated teeth and bone.
      Histopathological diagnosis of the en bloc tissue revealed an odontogenic
      fibromyxoma. Extensive literature review revealed few case reports of companion
      animals with this neoplasm, and none in a feline patient. This report documents
      the clinical presentation, diagnostic differentials, surgical therapy, and long
      term follow-up of an odontogenic fibromyxoma in a cat.

PMID- 28513314
TI  - Editorial.

PMID- 28513317
TI  - Engagement in Physical Activity During Recess: Gender and Grade Level Differences
      in the Elementary Grades.
AB  - BACKGROUND: There are many purported benefits to recess including engaging in
      physical activity, forming positive peer relationships, and taking a break from
      the classroom. Current research, however, is inconclusive regarding the presence
      of gender and developmental differences in physical activity that takes place
      during recess. The purpose of this study was to examine differences in the amount
      of physical activity that occurs during recess across gender and grade level.
      METHODS: Students from first- and sixth-grade classrooms participated in the
      study, and physical activity was measured using accelerometers to record the
      number of steps taken during recess. RESULTS: A 2 * 2 factorial ANOVA indicated
      sixth grade males engaged in more physical activity than sixth grade females,
      first grade males, and first grade females. CONCLUSIONS: Because they are not
      engaging in as much physical activity as their sixth grade male counterparts,
      ways to help female and younger students take more steps during recess should be
      explored.

PMID- 28513316
TI  - Childhood Socioeconomic Disadvantage, Occupational, Leisure-Time, and Household
      Physical Activity, and Diabetes in Adulthood.
AB  - BACKGROUND: Regular physical activity is a key way to prevent disease. However,
      we have a limited understanding of the socioeconomic precursors and
      glucoregulatory sequelae of engaging in physical activity in different domains.
      METHODS: We examined the associations among life course socioeconomic
      disadvantage; meeting the physical activity guidelines with leisure-time physical
      activity, occupational physical activity, or household physical activity; and
      prediabetes and diabetes in the Midlife in the United States national study (N =
      986). RESULTS: Childhood disadvantage was associated with lower odds of meeting
      the guidelines with leisure-time physical activity (odds ratio = 0.75; 95%
      confidence interval, 0.65-0.86). Adulthood disadvantage was associated with
      higher odds of meeting the guidelines with occupational physical activity (odds
      ratio = 1.94; 95% confidence interval, 1.49-2.53). Importantly, while meeting the
      guidelines with leisure-time physical activity was associated with lower odds of
      prediabetes and diabetes, we found no evidence for associations among
      occupational physical activity, household physical activity, and glucoregulation.
      CONCLUSION: Current US physical activity guidelines do not differentiate between
      physical activity for leisure or work, assuming that physical activity in any
      domain confers comparable health benefits. We documented important differences in
      the associations among lifetime socioeconomic disadvantage, physical activity
      domain, and diabetes, suggesting that physical activity domain potentially
      belongs in the guidelines, similar to other characteristics of activity (eg,
      type, intensity).

PMID- 28513318
TI  - Neighborhood Built Environment and Socioeconomic Status in Relation to Active
      Commuting to School in Children.
AB  - BACKGROUND: The role of neighborhood type in active commuting to school (ACS) has
      not been extensively studied in children. The purpose of this study was to
      analyze the association between neighborhood built environment (walkability) and
      neighborhood socioeconomic status (SES) with ACS among children. METHODS: A cross
      sectional study of 310 Spanish children (aged 10-12 y; 51% male) was conducted in
      2015. Walkability was defined as an index of 3 built environment characteristics
      (ie, residential density, land-use mix, and street connectivity) based on
      geographical information system data. Children's home and school neighborhoods
      were evaluated. ACS was evaluated by questionnaire. Mixed model regression
      analyses evaluated ACS in relation to neighborhood walkability and SES. RESULTS:
      There were no significant SES-walkability interactions for ACS. Children living
      in more walkable neighborhoods reported 2.5 more trips per week compared with
      those living in less walkable neighborhoods (P < .001). Children attending
      schools located in lower SES neighborhoods reported more ACS trips per week than
      those attending schools in higher SES neighborhoods (P < .05). CONCLUSIONS: Home
      neighborhood walkability and school-neighborhood SES were associated with ACS.
      This study highlights the importance of assessing children's home environment and
      school environment when ACS behavior is analyzed.

PMID- 28513319
TI  - Effect of surface functionalizations of multi-walled carbon nanotubes on
      neoplastic transformation potential in primary human lung epithelial cells.
AB  - Functionalized multi-walled carbon nanotube (fMWCNT) development has been
      intensified to improve their surface activity for numerous applications, and
      potentially reduce toxic effects. Although MWCNT exposures are associated with
      lung tumorigenesis in vivo, adverse responses associated with exposure to
      different fMWCNTs in human lung epithelium are presently unknown. This study
      hypothesized that different plasma-coating functional groups determine MWCNT
      neoplastic transformation potential. Using our established model, human primary
      small airway epithelial cells (pSAECs) were continuously exposed for 8 and 12
      weeks at 0.06 MUg/cm2 to three-month aged as-prepared-(pMWCNT), carboxylated-(MW
      COOH), and aminated-MWCNTs (MW-NHx). Ultrafine carbon black (UFCB) and
      crocidolite asbestos (ASB) served as particle controls. fMWCNTs were
      characterized during storage, and exposed cells were assessed for several
      established cancer cell hallmarks. Characterization analyses conducted at 0 and 2
      months of aging detected a loss of surface functional groups over time due to
      atmospheric oxidation, with MW-NHx possessing less oxygen and greater lung
      surfactant binding affinity. Following 8 weeks of exposure, all fMWCNT-exposed
      cells exhibited significant increased proliferation compared to controls at 7 d
      post-treatment, while UFCB- and ASB-exposed cells did not differ significantly
      from controls. UFCB, pMWCNT, and MW-COOH exposure stimulated significant
      transient invasion behavior. Conversely, aged MW-NHx-exposed cells displayed
      moderate increases in soft agar colony formation and morphological transformation
      potential, while UFCB cells showed a minimal effect compared to all other
      treatments. In summary, surface properties of aged fMWCNTs can impact cell
      transformation events in vitro following continuous, occupationally relevant
      exposures.

PMID- 28513320
TI  - CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras
      knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice.
AB  - Both Pten and Nras are downstream mediators of receptor tyrosine kinase
      activation that plays important roles in controlling cell survival and
      proliferation. Here, we investigated whether and how Pten loss cross-talks with
      Nras activation in driving liver cancer development in mice. Somatic disruption
      of hepatic Pten and overexpression of Nras were achieved in out-bred
      immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying
      Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated
      Pten knockout system. Concurrent Pten knockout and Nras knock-in induced
      hepatocellular carcinoma, while individual gene manipulation failed. Tumor
      development was associated with liver fibrosis, hyperlipidemia, hepatic
      deposition of lipid droplets and glycogen, and hepatomegaly. At the molecular
      level, lipid droplet formation was primarily contributed by upregulated
      expression of genes responsible for lipogenesis and fatty acid sequestration,
      such as Srebpf1, Acc, Pparg and its downstream targets. Our findings demonstrated
      that Pten disruption was synergized by Nras overexpression in driving hepatocyte
      malignant transformation, which correlated with extensive formation of lipid
      droplets.

PMID- 28513322
TI  - People with and without prosopagnosia have insight into their face recognition
      ability.

PMID- 28513321
TI  - Active Travel to and From School Among School-Age Children During 1997-2011 and
      Associated Factors in China.
AB  - BACKGROUND: Active travel to school (ATS) is positively associated with various
      health indicators. The rapid social, economic, and environmental changes in China
      provide a unique setting to study changes and predictors of ATS over time.
      METHODS: Using logistic regression modeling, we analyzed data from the China
      Health and Nutrition Survey during 1997 to 2011 (N = 9487, ages 6 to 17 years) to
      estimate the change over time in ATS and to identify associated factors. RESULTS:
      The prevalence of reported ATS among children dropped from 95.8% in 1997 to 69.3%
      in 2011. ATS was common in children living closer to school, in middle school,
      from low-income households, with low parental education status, and those without
      a private vehicle. Children who were living in a metropolitan area and who had
      more than 40 minutes of total PA per day were less likely to report ATS.
      CONCLUSIONS: The decrease of ATS had been concurrent with the increase of the
      children living at a longer distance from school and the increase of household
      owning private vehicles which were associated with the rapid urbanization and
      economic growth in China. Factors associated with the decreased ATS in China are
      similar to other countries but the underlying reasons may be different.

PMID- 28513323
TI  - Modulation of somatoparaphrenia following left-hemisphere damage.
AB  - Somatoparaphrenic symptoms after left-hemisphere damage are rare. To verify the
      potential role of body-related sensory (proprioceptive, visual, and
      somatosensory) manipulation in patients experiencing sensations of hand
      disownership, the symptoms of a patient suffering from right-hand
      somatoparaphrenia were monitored and clinical and neuropsychological variables
      were controlled. Four types of manipulation were administered: changes in spatial
      position of the hand, multisensory stimulation, and self-observation using video
      or mirrors. Multisensory visuo-tactile stimulation was efficacious in terms of
      reducing somatoparaphrenia, and changes in the position of the hand produced some
      positive effects. Third-person perspective self-observation did not, however,
      result in any changes.

PMID- 28513324
TI  - Biomechanical Comparison of Countermovement Jumps Performed on Land and in Water:
      Age Effects.
AB  - CONTEXT: The aquatic environment provides a low-impact alternative to land-based
      exercise and rehabilitation in older adults. OBJECTIVE: Evaluate the biomechanics
      of older adults and young adults performing jumping movements on land and in
      water. DESIGN AND SETTING: Cross-sectional, mixed-factorial experiment;
      adjustable-depth pool at sports medicine research facility. PARTICIPANTS: Fifty
      six young adults (age = 22.0 [3.9] y) and 12 healthy older adults (age = 57.3
      [4.4] y). INTERVENTIONS: Each participant performed 6 maximal effort
      countermovement jumps: 3 jumps were performed on land, and 3 other jumps were
      performed with participants immersed in chest-deep water. MAIN OUTCOME MEASURES:
      Using data from the amortization and propulsive phases of jumping, the authors
      computed the following kinetic and kinematic measures: peak and mean mechanical
      power, peak force, amortization time and rate, unweighting and propulsive times,
      and lower-extremity segment kinematics. RESULTS: Mechanical power outputs were
      greater in younger adults (peak: 7322 [4035] W) versus older adults (peak:
      5661.65 [2639.86] W) and for jumps performed in water (peak: 9387 [3981] W)
      versus on land (peak: 4545.84 [1356.53] W). Peak dorsiflexion velocities were
      greater for jumps performed in water (66 [34] deg/s) versus on land (4 [7]
      deg/s). The amortization rate was 26% greater in water versus on land. The
      amortization time was 20% longer in older adults versus young adults.
      CONCLUSIONS: Countermovement jumps performed in water are mechanically specific
      from those performed on land. Older adults jumped with longer unweighting times
      and increased mechanical power in water. These results suggest that aquatic-based
      exercise and rehabilitation programs that feature jumping movements may benefit
      older adults.

PMID- 28513326
TI  - The Effects of Blood Flow Restricted Electrostimulation on Strength and
      Hypertrophy.
AB  - CONTEXT: The combined effect of neuromuscular electrical stimulation (NMES) and
      blood flow restriction (BFR) on muscle mass and strength has not been thoroughly
      investigated. OBJECTIVE: To examine the effects of combined and independent BFR
      and a low-intensity NMES on skeletal muscle adaptation. DESIGN: Exploratory
      study. SETTING: Laboratory. PARTICIPANTS: Twenty recreationally active subjects.
      MAIN OUTCOME MEASURES: Subjects had each leg randomly allocated to 1 of 4
      possible intervention groups: (1) cyclic BFR alone, (2) NMES alone, (3) BFR +
      NMES, or (4) control. Each leg was stimulated in its respective intervention
      group for 32 minutes, 4 days per week for 6 weeks. Mean differences in size (in
      grams) and isometric strength (in kilograms), between week 0 and week 6, were
      calculated for each group. RESULTS: Leg strength increased 32 (19) kg in the BFR
      + NMES group, which differed from the 3 (11) kg change in the control group (P =
      .03). The isolated NMES and BFR groups revealed increases of 16 (28) kg and 18
      (17) kg, respectively, but these did not statistically differ from the control,
      or one another. No alterations were statistically significant for leg size.
      CONCLUSION: Compared with a control that received no treatment, the novel
      combination of BFR and NMES led to increasing muscular strength of the knee
      extensors, but not muscle mass which had a large interindividual variability in
      response.

PMID- 28513325
TI  - Developmental transitions in Arabidopsis are regulated by antisense RNAs
      resulting from bidirectionally transcribed genes.
AB  - Transcription terminators are DNA elements located at the 3' end of genes that
      ensure efficient cleavage of nascent RNA generating the 3' end of mRNA, as well
      as facilitating disengagement of elongating DNA-dependent RNA polymerase II.
      Surprisingly, terminators are also a potent source of antisense transcription. We
      have recently described an Arabidopsis antisense transcript originating from the
      3' end of a master regulator of Arabidopsis thaliana seed dormancy DOG1. In this
      review, we discuss the broader implications of our discovery in light of recent
      developments in yeast and Arabidopsis. We show that, surprisingly, the key
      features of terminators that give rise to antisense transcription are preserved
      between Arabidopsis and yeast, suggesting a conserved mechanism. We also compare
      our discovery to known antisense-based regulatory mechanisms, highlighting the
      link between antisense-based gene expression regulation and major developmental
      transitions in plants.

PMID- 28513327
TI  - Dolphin Morbillivirus in a Fin Whale (Balaenoptera physalus) in Denmark, 2016.
AB  - We studied the etiology of encephalitis in a fin whale (Balaenoptera physalus)
      that stranded in 2016 on the coast of Denmark. Dolphin morbillivirus (DMV) was
      detected in the brain and other organs. Phylogenetics showed close relation to
      DMV isolated from a striped dolphin (Stenella coeruleoalba) from Spain in 2012.

PMID- 28513328
TI  - TRYPANOSOMA CRUZI IN FREE-RANGING MAMMALIAN POPULATIONS IN SOUTH TEXAS, USA.
AB  - Chagas disease, also known as American trypanosomiasis, is caused by the
      flagellate protozoan Trypanosoma cruzi. It is a significant health concern in
      South and Central America, where millions of people are infected or at risk of
      infection, and is an emerging health concern in the US. The occurrence of Chagas
      disease in natural environments is supported by mammal host species, but those
      primary species may vary based on geographic location. In South Texas, the
      primary host species for the disease is poorly understood, and required a field
      study to determine the spatial distribution of T. cruzi prevalence in free
      ranging mammals. Our study objectives were to determine the spatial distribution
      and prevalence of T. cruzi parasites in free-ranging mammals. We compared T.
      cruzi prevalence among species, among vegetative communities, and among different
      topographies (i.e., floodplain versus upland). From December 2011 through
      December 2013, 450 blood and tissue samples from geolocated free-ranging wildlife
      mammal species were analyzed with the use of polymerase chain reaction to detect
      protozoan T. cruzi DNA. We also calculated mammal abundance with the use of mark
      recapture methodology and recorded capture-site characteristics such as
      vegetation structure. We found that animals in grasslands had a significantly
      lower infection rate when summed across all species compared with animals in
      dense hardwoods and semi-improved woodlands (P=0.001). A higher percentage of
      infections were found in the lower-elevation floodplain-65% (28/43) of animals
      sampled, compared to upland areas-25% (9/36) of animals sampled. Our study
      suggested that common free-ranging meso-mammals supported T. cruzi in natural
      environments and are of public health concern in South Texas. Mitigation
      strategies should consider a range of management activities to include vegetation
      management, selective application of insecticides, and changes in human behavior
      in high-risk areas.

PMID- 28513329
TI  - Serologic Detection of Subtype-specific Antibodies to Influenza A Viruses in
      Southern Sea Otters (Enhydra lutris nereis).
AB  - There are approximately 3,000 southern sea otters (Enhydra lutris nereis) in the
      nearshore environment along the California coast, US, and the species is
      classified as Threatened under the Endangered Species Act. We tested sera from
      661 necropsied southern sea otters sampled from 1997 to 2015 to determine overall
      exposure to influenza A viruses (IAVs) and to identify subtype-specific antibody
      responses. Using an enzyme-linked immunosorbent assay (ELISA), antibodies to IAV
      nucleoproteins were detected in 160 (24.2%) otters, with seropositive animals
      found in every year except 2008. When the ELISA-positive samples were tested by
      virus microneutralization, antibody responses were detected to avian-origin
      hemagglutinin subtypes H1, H3, H4, H5, H6, H7, H9, and H11. Strong antibody
      responses to pandemic H1N1 (pdmH1N1) were also detected, indicating that
      epizootic transmission of pdmH1N1 occurred among the southern sea otter
      population after the emergence of this human-origin virus in 2009. We conclude
      that southern sea otters are susceptible to infection with avian and human-origin
      IAV and that exposure to a wide array of subtypes likely occurs during a given
      otter's 10- to 15-yr life span. Important unanswered questions include what
      effect, if any, IAV infection has on sea otter health, and how these animals
      become infected in their nearshore environment.

PMID- 28513331
TI  - Tracking cell proliferation using a nanotechnology-based approach.
AB  - AIM: To develop an efficient nanotechnology fluorescence-based method to track
      cell proliferation to avoid the limitations of current cell-labeling dyes.
      MATERIAL & METHODS: Synthesis, PEGylation, bifunctionalization and labeling with
      a fluorophore (Cy5) of 200 nm polystyrene nanoparticles (NPs) were performed.
      These NPs were characterized and assessed for in vitro long-term monitoring of
      cell proliferation. RESULTS: The optimization and validation of this method to
      track long-term cell proliferation assays have been achieved with high
      reproducibility, without cell cycle disruption. This method has been successfully
      applied in several adherent and suspension cells including hard-to-transfect
      cells and isolated human primary lymphocytes. CONCLUSION: A novel approach to
      track efficiently cellular proliferation by flow cytometry using fluorescence
      labeled NPs has been successfully developed. [Formula: see text].

PMID- 28513330
TI  - THE PATHOGENESIS OF CLADE 2.3.4.4 H5 HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUSES IN
      RUDDY DUCK (OXYURA JAMAICENSIS) AND LESSER SCAUP (AYTHYA AFFINIS).
AB  - Waterfowl are the natural hosts of avian influenza virus (AIV) and disseminate
      the virus worldwide through migration. Historically, surveillance and research
      efforts for AIV in waterfowl have focused on dabbling ducks. The role of diving
      ducks in AIV ecology has not been well characterized. In this study, we examined
      the relative susceptibility and pathogenicity of clade 2.3.4.4 H5 highly
      pathogenic AIV (HPAIV) in two species of diving ducks. Juvenile and adult Ruddy
      Duck (Oxyura jamaicensis) and juvenile Lesser Scaup (Aythya affinis) were
      intranasally inoculated with A/Northern Pintail/WA/40964/2014 H5N2 HPAIV.
      Additional groups of juvenile Lesser Scaups were inoculated with
      A/Gyrfalcon/WA/41088/2014 H5N8 HPAIV. The approximate 50% bird infectious doses
      (BID50) of the H5N2 isolate for adult Ruddy Ducks was <102 50% egg infectious
      doses (EID50) and for the juvenile Lesser Scaups it was <104 EID50. There were
      insufficient juvenile Ruddy Ducks to calculate the BID50. The BID50 for the
      juvenile Lesser Scaups inoculated with the H5N8 isolate was 103 EID50. Clinical
      disease was not observed in any group; however, mortality occurred in the
      juvenile Ruddy Ducks inoculated with the H5N2 virus (three of five ducks), and
      staining for AIV antigen was observed in numerous tissues from these ducks. One
      adult Ruddy Duck also died and although it was infected with AIV (the duck was
      positive for virus shedding and AIV antigen was detected in tissues), it was also
      infected with coccidiosis. The proportion of ducks shedding virus was related to
      the dose administered, but the titers were similar among dose groups. The group
      with the fewest ducks shedding virus was the adult Ruddy Ducks. There was a trend
      for the Lesser Scaups to shed higher titers of virus than the Ruddy Ducks. No
      virus shedding was detected after 7 d postinoculation in any group. Similar to
      dabbling ducks, Lesser Scaups and Ruddy Ducks are susceptible to infection with
      this H5 HPAIV lineage, although they excrete lower titers of virus.

PMID- 28513332
TI  - A fit-for-purpose method to monitor 16 European Union PAHs in food: results of
      five years of official food control in two Italian regions.
AB  - A gas-chromatographic single-quadrupole analytical method for the analysis of the
      16 priority European Union (EU) polycyclic aromatic hydrocarbons (PAHs) in food
      is presented. The method fulfils the request of Regulation EU 836/2011 for an
      analytical procedure to be used for official control of PAHs in food in EU member
      states. The sample preparation involves a pressurised liquid extraction (PLE)
      with an in-cell clean-up step followed by a lipid removal using solid-phase
      extraction (SPE) on a styrene divinylbenzene stationary phase (SDVB) and a final
      gel-permeation chromatography (GPC) step. To reach a better sensitivity for all
      the analytes, including the heaviest last eluting PAHs, 3 MUl of the purified
      extract were injected in solvent vent mode using a programmable temperature
      vaporization (PTV) injector. The isobaric PAH isomers were successfully separated
      using an Agilent Technologies DB-17MS (20 m * 0.18 mm * 0.18 MUm) column. The
      method was fully validated using an in-house approach and the sensitivity,
      accuracy and precision obtained were satisfactory. The method expanded
      uncertainty was estimated and it was verified that it was below the maximum
      standard measurement uncertainty. Moreover, the results of 347 samples of meat
      and meat products, fish and fish products and mussels collected from January 2012
      to December 2016 in the Marche and Umbria regions of Italy are reported. None of
      the samples exceed the maximum levels fixed by EU Regulation 835/2011, and clams
      turned out to be the most contaminated among the food matrices analysed. Finally,
      an estimate of the sum of four marker PAHs (benzo[a]anthracene,
      benzo[b]fluoranthene, benzo[a]pyrene, chrysene) as indicator of the PAHs
      contamination was done by comparison with the 16 carcinogenic PAHs sum.

PMID- 28513334
TI  - Benefits of ion mobility for analysing monochloropropane-diol esters.
AB  - This paper reports the first application and benefits of ion mobility in
      combination with liquid chromatography and a transportable time-of-flight mass
      spectrometer to the analysis of monochloropropane-diol esters (MCPDE) in
      vegetable oils. The additional selectivity obtained with the ion mobility allowed
      the quantitative analysis of MCPDEs as such in their intact form (direct
      analysis) without any chemical derivatisation and, furthermore, without any
      enrichment or purification step. This gain in selectivity manifests primarily in
      the resolution of interferences originating, for example, from the diacylglycerol
      components of palm oil. In silico calculations confirm that resolution of such
      interferences would require mass resolutions higher than 200,000 at m/z 600,
      e.g., in the case of signals of the 41K isotope of the PO DAG and the signals of
      the sodiated PO MCPD. While such resolution can be obtained on certain state-of
      the-art costly and laboratory-exhaustive research instruments, this study
      demonstrates that even transportable time-of-flight MS can achieve the required
      selectivity when combined with ion mobility. Further advantage of the described
      approach is that the applied sample preparation is only dilution with minimum
      consumable requirements and can be performed quickly even outside laboratories
      directly in the field. The described results suggest that the application of ion
      mobility in addition to LC-MS is likely to push the boundaries of contaminant
      analysis especially for high-throughput screening investigations.

PMID- 28513333
TI  - Atg9a deficiency causes axon-specific lesions including neuronal circuit
      dysgenesis.
AB  - Conditional knockout mice for Atg9a, specifically in brain tissue, were generated
      to understand the roles of ATG9A in the neural tissue cells. The mice were born
      normally, but half of them died within one wk, and none lived beyond 4 wk of age.
      SQSTM1/p62 and NBR1, receptor proteins for selective autophagy, together with
      ubiquitin, accumulated in Atg9a-deficient neurosoma at postnatal d 15 (P15),
      indicating an inhibition of autophagy, whereas these proteins were significantly
      decreased at P28, as evidenced by immunohistochemistry, electron microscopy and
      western blot. Conversely, degenerative changes such as spongiosis of nerve fiber
      tracts proceeded in axons and their terminals that were occupied with aberrant
      membrane structures and amorphous materials at P28, although no clear-cut
      degenerative change was detected in neuronal cell bodies. Different from
      autophagy, diffusion tensor magnetic resonance imaging and histological
      observations revealed Atg9a-deficiency-induced dysgenesis of the corpus callosum
      and anterior commissure. As for the neurite extensions of primary cultured
      neurons, the neurite outgrowth after 3 d culturing was significantly impaired in
      primary neurons from atg9a-KO mouse brains, but not in those from atg7-KO and
      atg16l1-KO brains. Moreover, this tendency was also confirmed in Atg9a-knockdown
      neurons under an atg7-KO background, indicating the role of ATG9A in the
      regulation of neurite outgrowth that is independent of autophagy. These results
      suggest that Atg9a deficiency causes progressive degeneration in the axons and
      their terminals, but not in neuronal cell bodies, where the degradations of
      SQSTM1/p62 and NBR1 were insufficiently suppressed. Moreover, the deletion of
      Atg9a impaired nerve fiber tract formation.

PMID- 28513335
TI  - TiO2/UV-assisted rhodamine B degradation: putative pathway and identification of
      intermediates by UPLC/MS.
AB  - The present study was designed to evaluate the photocatalytic degradation of
      Rhodamine B (Rh-B) in a self-assembled TiO2-assisted system under UV light
      irradiation. Chemical oxygen demand, total organic carbon and high-performance
      liquid chromatography analyses confirmed the elevated Rh-B degradation level. A
      stepwise meticulous breakdown pathway based on the ultra-performance liquid
      chromatography coupled with electrospray ionization mass spectrometry is
      proposed. Results demonstrated that the degradation of Rh-B mainly occurred via N
      de-ethylation process, and N-de-ethylated intermediate products were further
      oxidized into acids and alcohols. Reduction in toxicity of the dye by the
      formation of metabolites was measured using human cell lines (MTT assay) and
      toxicity tests based on shrimp Artemia salina. Noticeably, the degraded
      intermediates of Rh-B revealed low or non-toxicity than the original dye
      molecule. Therefore, it can be inferred that the TiO2-assisted photocatalysis
      could be beneficial for the degradation of recalcitrant compounds and textile
      wastewater effluents, and for the elimination of toxicity therein.

PMID- 28513336
TI  - Use of Tenax(r) films to demonstrate the migration of chemical contaminants from
      cardboard into dry food.
AB  - Contaminants in food packaging are a challenge of our time since the packaging
      material itself has been found to represent a source of food contamination
      through the migration of substances from it. Before first use, packaging
      materials destined for the packaging of dry foods can be evaluated by performing
      migration experiments with the simulant for dry foods, Tenax(r). This simulant is
      commercially available as a powder that is more difficult to handle during the
      migration experiments. This paper reports the development of a Tenax film. The
      film can be applied to the cardboard surface to conduct the migration test. After
      the migration is completed, the film can be easily extracted to determine the
      concentration of the contaminants in the film. Finally, the performance of the
      Tenax film was compared with the conventional Tenax powder for the evaluation of
      15 model migrants.

PMID- 28513337
TI  - Assessment of applicability index for better management of municipal solid waste:
      a case study of Dhanbad, India.
AB  - Selection of suitable municipal solid waste management (MSWM) options is one of
      the major challenges in urban areas of the developing countries. Success of MSWM
      requires accurate data of generation rate, composition and physico-chemical
      characteristics of solid wastes. Improper handling of solid waste can have
      significant environmental and aesthetical impacts. The present study proposes a
      new method (applicability index - Pik values) for identifying the most
      appropriate disposal option with the help of applicability values of Composting
      CP, Incineration-IP and Landfill-LP for individual components of MSW based on the
      results of the physico-chemical analysis of the collected representative solid
      waste samples from the study area, Dhanbad, India. The mean values of moisture
      content, carbon, hydrogen, oxygen, nitrogen, sulfur, volatile organic carbon,
      fixed carbon, ash content, density and calorific values (CV) of individual
      components were used as input values in this process. Based on the proposed
      applicability index (Pik), the highest Pik values were obtained for incineration
      (IP) for plastics, polythene, paper, coconut shell, wood, cardboard, textile,
      thermocol (polystyrene), rubber, sugarcane bagasse, cow dung and leather wastes
      (IP > CP > LP) due to high CV of these solid waste components; the highest Pik
      values were obtained for composting (CP) of kitchen waste (CP > IP > LP); and the
      highest Pik values for inert wastes were obtained for landfill option (LP > IP >
      CP). The highest Pik value for a particular waste for a specific treatment option
      signifies that the waste is suitable for treatment/disposal using that option.

PMID- 28513339
TI  - Juggling thoughts and feelings: How do female patients with borderline
      symptomology and substance use disorder experience change in mentalization-based
      treatment?
AB  - OBJECTIVE: The aim of this study was to explore the experience of central
      psychological change processes for female patients with borderline symptomology
      and substance use disorder in mentalization-based treatment. METHOD: Semi
      structured qualitative interviews on experiences from mentalization-based
      treatment with 13 participants were conducted. The interview material was
      analysed within a hermeneutical-phenomenological epistemology, with emphasis on
      researcher reflexivity. RESULTS: The following themes regarding central
      psychological change processes were found: "by feeling the feeling," "by thinking
      things through," "by walking in your shoes to see myself" and "by stepping
      outside of own bad feelings in seeing you." Two of these themes dealt with intra
      psychic modes of how to relate to own mind-states. First, they had a shift from
      avoiding emotions into tolerating emotions. Second, they discovered the ability
      to think mental states through. Two themes dealt with mental stances for dealing
      with interpersonal situations, where one mode included a self-reflective stance
      in difficult encounters, and the other mode entailed an empathic reflective
      stance by exploring others' intentionality. CONCLUSIONS: The findings are in line
      with theoretical assumptions that increasing mentalizing capacity is a central
      change process for these patients. Furthermore, the findings demonstrate the
      complex interaction between different modes of mentalizing.

PMID- 28513338
TI  - Worldwide Surveillance, Policy, and Research on Physical Activity and Health: The
      Global Observatory for Physical Activity.
AB  - BACKGROUND: The Global Observatory for Physical Activity (GoPA!) was launched in
      response to the physical inactivity pandemic. The aim of this article is to
      present current information about surveillance, policy, and research on physical
      activity (PA) and health worldwide. METHODS: Information was collected for 217
      countries. For 139 of these nations we identified a contact who confirmed
      information's accuracy and completeness. Associations were calculated among
      surveillance, policy and research categories. RESULTS: Of the 139 countries,
      90.6% reported having completed 1 or more PA survey, but less than one-third had
      3 or more. 106 included PA on a national plan, but only one-quarter of these were
      PA-specific. At least 1 peer reviewed publication was identified for 63.3% of the
      countries. Positive associations (P < .001) were found between research and
      policy (rho = 0.35), research and surveillance (rho = 0.41), and surveillance and
      policy (rho = 0.31). Countries with a standalone plan were more likely to have
      surveillance. Countries with more research were more likely to have a standalone
      plan and surveillance. CONCLUSIONS: Surveillance, policy, and research indicators
      were positively correlated, suggesting that action at multiple levels tends to
      stimulate progress in other areas. Efforts to expand PA-related surveillance,
      policy, and research in lower income countries are needed.

PMID- 28513341
TI  - Adolescent Pregnancy and Increasing Body Mass Index: Risks and Benefits.

PMID- 28513340
TI  - Questions About Cervical and Breast Cancer Screening Knowledge, Practice, and
      Outcomes: A Review of Demographic and Health Surveys.
AB  - United Nation's Sustainable Development Goals and the World Health Organization's
      Global Monitoring Framework support a strong global commitment to reducing the
      high burden of cervical and breast cancers among low- and middle-income
      countries. Strategies include vaccination, screening, and early diagnosis.
      Population-based surveys, such as those conducted by the Demographic and Health
      Surveys (DHS) Program, can collect the information needed to guide cancer control
      efforts in a standardized comparable manner. We identified and evaluated the
      breadth of breast and cervical cancer screening information that was collected by
      the DHS from 1984 through 2015. Then, we determined if these surveys currently
      provide the specific and measurable data about both the quantity and quality of
      cancer screening needed to guide national efforts to reduce the overall effects
      of cervical and breast cancers. We searched the DHS website to identify surveys
      conducted between the start of the DHS Program in 1984 and November 2015 that
      included questions about breast and cervical cancer screening. The relevant
      questions were extracted from the questionnaire, translated into English, and
      grouped by themes. Of the 90 countries where DHS surveys have been implemented,
      cervical cancer screening questions were included in 22 countries (24.4%) and
      breast cancer screening questions in 18 countries (20.0%). The common themes
      identified were disease knowledge, screening knowledge, screening practice, and
      screening outcomes. Most countries with survey questionnaires available for
      review addressed at least one aspect of screening practice (88.9% of cervical and
      87.5% of breast), although few countries queried knowledge and outcomes.
      Questions that assess varied aspects of breast and cervical cancer screening have
      been incorporated into relatively few DHS surveys. The themes identified could
      guide the design of a standard set of questions for use in future population
      based surveys and enable evaluation beyond the existence of screening, which
      would include assessment of the quality and impact of cervical and breast cancer
      screening.

PMID- 28513342
TI  - Integration in the Psychodynamic Psychotherapy of Severe Personality Disorders:
      The Conversational Model.
AB  - The psychotherapy of commonly occurring severe personality disorders-borderline,
      narcissistic, avoidant, dependent, obsessive compulsive, and schizoid-presents
      the therapist with a unique therapeutic challenge, as each personality disorder
      rarely occurs alone. Integration of what is most useful and what works in each
      model is being proposed to enable a more successful approach to the diversity of
      presentations. We describe the conversational model, some outcome research, and
      descriptive studies to illustrate this. Based in psychoanalytic theory, the
      conversational model is integrated with trauma theory, findings in memory
      research, linguistics, neurophysiological data, and, above all, on the
      observations of clinical experiences. Our emphasis in this article is on the
      treatment principles, methods, and techniques, along with case examples to
      illustrate what we mean. Case material is taken from audio recordings for which
      written informed consent was obtained for presentations and journal articles.
      Some changes have been made to maintain confidentiality.

PMID- 28513343
TI  - The Impact of Social Exclusion on "Reading the Mind in the Eyes" Performance in
      Relation to Borderline Personality Disorder Features.
AB  - In this study we used the Reading the Mind in the Eyes Test (RMET) to explore
      facial emotion recognition in borderline personality disorder (BPD). We also used
      Cyberball, a computerized task designed to mimic social ostracism, to examine the
      response of BPD-feature participants to social exclusion. Seventeen individuals
      with BPD features were compared to 16 healthy controls on RMET performance pre-
      and post-exclusion via Cyberball. Our results revealed a significant interaction
      between BPD-feature status and RMET performance in relation to neutral stimuli
      following a social exclusion experience. BPD participants' ability to correctly
      identify neutral faces significantly decreased following exclusion. This finding
      suggests that once an individual with BPD features experiences a social exclusion
      event, his or her objectivity decreases and affective valence is ascribed to
      stimuli previously perceived as neutral. Our results may help to explain, in
      part, the social instability seen in BPD.

PMID- 28513344
TI  - Pathological Narcissism and Nonsuicidal Self-Injury.
AB  - Few studies have examined associations between pathological narcissism and self
      harm, but those that do indicate that narcissistic vulnerability (not
      narcissistic grandiosity) relates to self-harm. The current study extends this
      literature by investigating how facets of pathological narcissism assessed by the
      Pathological Narcissism Inventory relate to specific nonsuicidal self-injury
      (NSSI) behaviors assessed by the Inventory of Statements About Self-Injury using
      statistical models appropriate for non-normally distributed count data. In a
      sample of 1,023 undergraduate students, results revealed that facets of both
      narcissistic vulnerability and narcissistic grandiosity were differentially
      related to the endorsement and frequency of specific NSSI behaviors and higher
      order latent NSSI factors (repetitive and impulsive), even after accounting for
      levels of borderline pathology. The clinical implications of these results are
      discussed.

PMID- 28513345
TI  - Borderline Personality Disorder Features and Sensitivity to Injustice.
AB  - Hypersensitivity to injustice has been proposed to contribute to interpersonal
      dysfunction in borderline personality disorder (BPD). We investigated whether BPD
      features are related to sensitivity to injustice and whether justice sensitivity
      mediates the relationship between BPD features and aggressive behavior. In an
      online survey, subjects reported justice sensitivity from the perspective of a
      victim, an observer, a beneficiary, and a perpetrator as well as BPD features and
      their own aggressive behavior. Justice sensitivity was higher in participants
      with a clinically relevant degree of BPD features when they evaluated injustice
      from the perspective of a victim or an observer. Victim sensitivity partially
      mediated the relationship between BPD features and the frequency of aggressive
      behavior. The present study provides first data on the important role of
      sensitivity to injustice in those with marked BPD features. Particularly, victim
      sensitivity with its close link to angry reactions may contribute to
      interpersonal problems in BPD.

PMID- 28513347
TI  - Development and Initial Validation of an Inconsistent Responding Scale for the
      Youth Psychopathic Traits Inventory.
AB  - The Youth Psychopathic Traits Inventory (YPI) is widely used in research, but
      there currently exist no means to identify potentially invalid protocols
      resulting from careless or random responding. We describe the development of an
      inconsistent responding scale for the YPI using three archival samples of youths,
      including two from the United States (juvenile justice and middle school) and one
      from Germany (vocational training school). We first identified pairs of
      correlated YPI items and then created a total score based on the sum of the
      absolute value of the differences for each item pair. The resulting scale
      strongly differentiated between genuine protocols and randomly generated YPI data
      (n = 1,000) across samples (AUC values = .88-.92). It also differentiated between
      genuine protocols and those same protocols after 50% of the original YPI items
      were replaced with random data (AUCs = .77-.84). Scores on this scale also
      demonstrated fairly consistent patterns of association with theoretically
      relevant correlates.

PMID- 28513346
TI  - Psychoeducation and Problem Solving (PEPS) Therapy for Adults With Personality
      Disorder: A Pragmatic Randomized-Controlled Trial.
AB  - We compared psychoeducation and problem solving (PEPS) therapy against usual
      treatment in a multisite randomized-controlled trial. The primary outcome was
      social functioning. We aimed to recruit 444 community-dwelling adults with
      personality disorder; however, safety concerns led to an early cessation of
      recruitment. A total of 154 people were randomized to PEPS and 152 to usual
      treatment. Follow-up at 72 weeks was completed for 68%. PEPS therapy was no more
      effective than usual treatment for improving social functioning (adjusted
      difference in mean Social Functioning Questionnaire scores = -0.73; 95% CI [
      1.83, 0.38]; p = 0.19). PEPS therapy is not an effective treatment for improving
      social functioning of adults with personality disorder living in the community.

PMID- 28513348
TI  - Measurement Invariance Between Genders on Two Measures of Borderline Personality
      Disorder.
AB  - Gender bias in the diagnosis and assessment of borderline personality disorder
      (BPD) has been the subject of much controversy in the psychological research
      literature. Evidence regarding differential prevalence rates and diagnostic rates
      in clinical settings between genders has been mixed, and measurement bias is one
      potential explanation for these mixed findings. A total of 340 participants were
      recruited from a Midwestern university and four outpatient community mental
      health clinics. They were administered two structured clinical interviews for BPD
      that were then evaluated for measurement invariance. Both the SCID-II BPD scale
      and the PDI-IV BPD scale were found to be measurement invariant between genders.
      No significant differences were found on the SCID-II BPD scale in diagnosis or
      overall number of criteria endorsed. However, in the rates of endorsement of
      individual criteria, differences were found in the unstable relationships item.

PMID- 28513349
TI  - Development and Psychometric Properties of the Standardized Assessment of
      Severity of Personality Disorder (SASPD).
AB  - Personality disorder (PD) is increasingly categorized according to its severity,
      but there is no simple way to screen for severity according to ICD-11 criteria.
      We set out to develop the Standardized Assessment of Severity of Personality
      Disorder (SASPD). A total of 110 patients completed the SASPD together with a
      clinical assessment of the severity of personality disorder. We examined the
      predictive ability of the SASPD using the area under the ROC curve (AUC). Two to
      four weeks later, 43 patients repeated the SASPD to examine reliability. The
      SASPD had good predictive ability for determining mild (AUC = 0.86) and moderate
      (AUC = 0.84) PD at cut points of 8 and 10, respectively. Test-retest reliability
      of the SASPD was high (intraclass correlation coefficient = 0.93, 95% CI [0.88,
      0.96]). The SASPD thus provides a simple, brief, and reliable indicator of the
      presence of mild or moderate PD according to ICD-11 criteria.

PMID- 28513350
TI  - Examining the Relationships Between the Triarchic Psychopathy Constructs and
      Behavioral Deviance in a Community Sample.
AB  - Few studies have examined the extent to which psychopathic traits relate to the
      commission of mild to moderate acts of deviance, such as vandalism and minor
      traffic violations. Given that psychopathy is now studied in community
      populations, the relationship between psychopathic traits and less severe deviant
      behaviors, which are more normative among noninstitutionalized samples, warrants
      investigation. The current study examined the relationships between the triarchic
      model of psychopathy (Patrick, Fowles & Krueger, 2009) and seven forms of deviant
      behavior (drug use, alcohol use, theft, vandalism, school misconduct, assault,
      and general deviance) in a nationally representative sample. Triarchic
      disinhibition positively predicted each form of normative deviance. Boldness
      positively predicted drug and alcohol use as well as general deviance, while
      meanness negatively predicted school misconduct. Boldness and disinhibition also
      positively predicted overall lifetime engagement in deviant behavior.
      Implications are discussed, including support of the role of boldness within the
      psychopathy construct.

PMID- 28513354
TI  - Nurses' goodwill keeping NHS afloat, RCN warns.
AB  - Four in five NHS nursing directors in the UK are worried that their hospitals
      rely on the goodwill of staff to keep services running, according to research
      from the RCN.

PMID- 28513351
TI  - Mind the Fathers: Associations of Parental Childhood Adversities With Borderline
      Personality Disorder Pathology in Female Adolescents.
AB  - Previous research revealed significant relations between the experience of
      childhood adversity (CA) and the development of borderline personality disorder
      (BPD) in adulthood. However, it is still uncertain whether parental CA could have
      a transgenerational association with adolescent BPD. We investigated associations
      between parents' CA (antipathy, neglect, physical abuse) and BPD traits within a
      clinical adolescent sample and tested for mediating variables. The sample
      consists of 91 female inpatients, along with 84 mothers and 59 fathers.
      Adolescent BPD traits were assessed using the BPD module of the Structured
      Clinical Interview for DSM-IV Disorders (SCID-II). Adolescent and parental CA and
      parental subclinical BPD traits were measured using validated self-report
      questionnaires (CECA.Q; PSSI). The findings revealed significant associations
      between parental CA and adolescent BPD traits, which were partially mediated by
      parental subclinical BPD traits and by paternal but not maternal CA. The results
      underline that early intervention of BPD must target the family environment,
      including fathers.

PMID- 28513355
TI  - Student-mentor friction debated.
AB  - Nursing students' challenging behaviour towards mentors was the subject of a
      debate at RCN congress.

PMID- 28513352
TI  - What impact does antenatal and postnatal care have on neonatal deaths in low- and
      lower-middle-income countries? Evidence from Bangladesh.
AB  - We investigated the contribution of antenatal and postnatal care in reducing the
      risk of neonatal deaths in Bangladesh. The effects of these services were
      examined using adjusted Cox regression models and secondary data with 7,314 live
      born infants. We observed that neonatal mortality was significantly decreased for
      newborns whose mothers' attended antenatal care services but postnatal care did
      not show any effect. Health promotion programs offering antenatal care in
      Bangladesh and other low- and lower-middle-income countries may build awareness
      about these practices. Further research is required to examine the reasons for
      the lack of impact of postnatal care on mortality.

PMID- 28513356
TI  - FamilyPlug.
AB  - This is the first communication app for patients with severe physical
      disabilities who are in an immobilised and semiconscious state. It allows the
      user's voice to reach the patient to help reduce feelings of isolation.

PMID- 28513357
TI  - Nursing students' experience of research during clinical placements.
AB  - Aim To investigate pre-registration nursing students' experience of research
      during clinical placements, and to identify any positive aspects or barriers to
      gaining experience of research during clinical placements. Method Qualitative,
      phenomenological, semi-structured interviews were undertaken with preregistration
      degree-level nursing students. The students were attending one university in the
      east of England, and were on clinical placements at one of three hospital sites
      in two trusts. Data were reviewed using thematic analysis. Findings The main
      themes that emerged from the interview data were: visibility, mentor influence,
      placement culture, student mindset, and role of the university. The study
      participants provided suggestions that could be adopted by universities and
      trusts to improve nursing students' experience of research during clinical
      placements, such as increasing opportunities to shadow research teams,
      introducing research earlier in the pre-registration course, and including a
      practical research module in the course. Conclusion Nursing students' experience
      of research during their clinical placements varied. It is important for trusts
      and universities to identify ways to improve nursing students' experience of
      research and to enhance their research learning, since research activity drives
      innovation and best practice.

PMID- 28513358
TI  - Workplace violence is unacceptable.
AB  - 'No one should feel threatened in the workplace for simply doing their job,' said
      the newspaper report.

PMID- 28513359
TI  - 'Innovations in your Specialty award winner helped save my life'.
AB  - 'Diane has given me strength and courage when I had nothing more than suicidal
      thoughts and, slowly but surely, she has helped me to piece together my life,'
      says Simon Peacock. 'She did this by keeping her word. She believed in me. She
      followed up referrals. She listened.'

PMID- 28513360
TI  - Student life - Be an agent of compassion.
AB  - [Figure: see text] The true definition of compassion is 'to be with suffering'.
      But in reality, compassion demands much more than simply being with suffering. It
      requires agency to help another get through it. Therefore, compassion requires an
      agent. An agent is defined as 'a person who acts on behalf of another person',
      and 'a person or thing that acts or has the power to act'.

PMID- 28513363
TI  - Wales keeps a welcome for students.
AB  - A campaign has been launched promoting Wales as a place for nurses to train, work
      and live.

PMID- 28513361
TI  - Readers' panel - Will the general election lead to a better deal for nurses?
AB  - Our experts consider a hot topic of the day.

PMID- 28513364
TI  - NHS Providers urges new government to address workforce shortages.
AB  - Unsafe staffing levels and poor pay are compromising patient care, healthcare
      providers have warned.

PMID- 28513365
TI  - No safety net.
AB  - What is the point of the royal family publicising mental health issues when care
      services in this specialty are not there when needed?

PMID- 28513366
TI  - Nurses wearing body cams.
AB  - This is inconceivable in mental health settings. Can you imagine an acutely
      unwell individual with paranoid and psychotic symptoms being seen by a nurse
      wearing a body cam? Not to mention issues around confidentiality.

PMID- 28513367
TI  - A sense of belonging unites Queen's Nurses.
AB  - In 1893, Florence Nightingale said hospitals are 'only an intermediate stage of
      civilization, never intended at all even to take in the whole sick population'.

PMID- 28513368
TI  - Credit where it's due.
AB  - Will staff in care homes ever receive thanks for their hard work and dedication?

PMID- 28513370
TI  - Tick-box spirituality.
AB  - The continued support for nurses in the delivery of spiritual care is to be
      welcomed (opinion, 12 April; evidence & practice, 19 April). However, I remain
      sceptical about the inclination to produce nursing process-type forms of
      spiritual assessment. If you have to use a form to assess a patient's spiritual
      needs, should you be asking at all?

PMID- 28513369
TI  - Confidentiality issues.
AB  - The first thing you need to do is seek approval from the relevant person at the
      practice. This could be your line manager, the practice manager or one of the
      partners. Once permission is in place, and if you want your son's friend to
      observe you as you work, there are two main areas that could pose a problem:
      patient consent and confidentiality.

PMID- 28513371
TI  - Letter.
AB  - There are many implications for patient dignity and confidentiality if staff wear
      body cams, but if interactions are recorded it could help prevent difficult
      situations from escalating.

PMID- 28513373
TI  - Philip, a prince among men.
AB  - Following the announcement that Prince Philip will withdraw from public duties, I
      should like to place on record the gratitude of male nurses when, as patron of
      the Society of Registered Male Nurses, he encouraged the career development of
      men in the profession.

PMID- 28513375
TI  - Helping victims of modern slavery.
AB  - I was volunteering at a refugee centre when a woman told me she was the happiest
      she could remember being. She said she had previously been a slave, and no matter
      how bad I thought her situation was now, it was always better than her past.

PMID- 28513374
TI  - Bursaries and safe staffing legislation top Corbyn's election pledges at
      congress.
AB  - Nursing student bursaries will be reinstated and NHS staff from the European
      Union (EU) given the right to remain if Labour wins the general election, Jeremy
      Corbyn has pledged.

PMID- 28513376
TI  - People who speak up must be celebrated.
AB  - From my own experience and conversations with other NHS whistleblowers, I am
      acutely aware of the fear that can consume you before and after raising concerns.
      Many health service staff believe they will lose their job, or at the very least
      be prevented from progressing in their career if they speak out.

PMID- 28513377
TI  - An important specialism.
AB  - Inflammatory bowel disease (IBD) nurse specialists provide invaluable support and
      expertise to patients to help improve their quality of life and give them more
      control over their treatment.

PMID- 28513378
TI  - Research identifies new way to attack breast cancer cells.
AB  - A study has revealed a new method for attacking the growth of cancer cells, after
      researchers discovered a protein that drives the spread of breast cancer.

PMID- 28513380
TI  - Plain packaging for cigarettes 'could cut smoker numbers'.
AB  - Plain cigarette packaging could reduce the number of people who smoke, research
      suggests.

PMID- 28513379
TI  - How to minimise the stress of relocating.
AB  - When it comes to stability, security and routine, your home and your work are
      vital. When you change the two at once, the stresses multiply.

PMID- 28513381
TI  - Cancer Drugs Fund was not a cost-effective use of NHS funds.
AB  - The NHS Cancer Drugs Fund (CDF) was not good value for patients or society and
      may have led to unnecessary side effects, researchers have found.

PMID- 28513383
TI  - Fructose intake in pregnancy linked to childhood obesity.
AB  - A diet high in fructose-containing sugars during pregnancy or breastfeeding may
      increase children's chances of developing obesity or type 2 diabetes, new
      research results suggest.

PMID- 28513382
TI  - Make nursing an election issue, Davies tells congress.
AB  - UK-WIDE legislation on safe staffing is needed to protect patients and the
      profession, RCN general secretary Janet Davies told this week's RCN congress.

PMID- 28513384
TI  - Pedometer challenge.
AB  - Nurses put their best feet forward for a pedometer challenge during RCN congress.

PMID- 28513385
TI  - Scrap the cap or jeopardise patient safety.
AB  - After the general election, for the sake of patient safety, the government must
      scrap the cap on nurses' pay and help to fill the 40,000 vacant jobs. These are
      not my words, but those of RCN general secretary Janet Davies, and summarise the
      college's key message to the political parties in the run-up to polling day on 8
      June.

PMID- 28513386
TI  - 'Working with nurses in Myanmar opened my eyes'.
AB  - When paediatric nurse Jennifer Sims decided in 2015 that she wanted to take on a
      new career challenge overseas, she got more than she bargained for.

PMID- 28513387
TI  - 'I wanted to be a Blue Peter presenter'.
AB  - Ruth Butler qualified as a registered general nurse and registered sick
      children's nurse in the 1980s, working at London's Great Ormond Street Hospital
      for Children NHS Trust. Last year, she was crowned winner of the child health
      award at the RCNi Nurse Awards, and has been in her current role as research
      associate at Central London Community Healthcare NHS Trust since October 2016.

PMID- 28513388
TI  - Cerebral palsy.
AB  - New guidelines from the National Institute for Health and Care Excellence (NICE)
      focus on children with cerebral palsy.

PMID- 28513389
TI  - TB: not just a disease of the past.
AB  - According to TB nurse manager Margaret Ogedengbe, getting the message across that
      tuberculosis (TB) is still a real and present danger in the UK is tough, because
      many people simply don't believe it.

PMID- 28513391
TI  - Body cameras help to reduce violence on wards.
AB  - Nurses who wore body cameras at work have praised the technology after a three
      month trial.

PMID- 28513393
TI  - Further study opens up career opportunities.
AB  - In the 1970s, only about one in 20 nurses in the had a degree, and the necessity
      of such an academic requirement was often viewed with derision. Now, as an all
      graduate profession, the importance of a master's degree for career progression
      takes on greater potency.

PMID- 28513395
TI  - Children less physically active as they progress through school.
AB  - Children spend less time doing physical activity as they progress through primary
      school, research has found.

PMID- 28513396
TI  - Acute pulmonary oedema.
AB  - What was the nature of the CPD activity, practice-related feedback and/or event
      and/or experience in your practice? The article provided information about the
      pathology, recognition, assessment and management of acute pulmonary oedema.

PMID- 28513397
TI  - Congress backs 'summer of protest' over pay.
AB  - Nurses across the UK could be set for a historic summer of protest after an RCN
      poll revealed strong support for strikes over pay restraint. The college warned
      that unless the next government scraps the 1% pay cap it will hold a ballot on
      industrial action later this year, threatening the first ever members' strikes in
      the RCN's 100-year history.

PMID- 28513398
TI  - 'Nurse believed in me and helped me piece my life back together'.
AB  - While serving in the Royal Anglian Regiment in Afghanistan in 2007, I was
      seriously injured by friendly fire. I was left with significant physical and
      psychological injuries from the blast.

PMID- 28513399
TI  - Reducing health inequalities for people with serious mental illness.
AB  - People with serious mental illness (SMI) are at risk of dying many years earlier
      than the general population. Providing an effective, cost-efficient healthcare
      service requires a holistic approach, and improving the physical health of people
      with SMI should be integral to all healthcare roles. It is important for nurses
      to identify and understand the barriers that people with SMI may experience when
      accessing physical healthcare. A range of factors contribute to reduced life
      expectancy, including lifestyle factors, symptoms of mental illness and the side
      effects of medications. This article discusses four areas of health that commonly
      affect people with SMI: metabolic syndrome, smoking, oral health and sexual
      health. Metabolic syndrome is a cluster of risk factors that increase an
      individual's risk of cardiovascular disease, stroke and type 2 diabetes mellitus.
      Smoking is increasingly prevalent in people with SMI, with rates remaining steady
      despite a decline in smoking rates nationally. Oral health and sexual health can
      negatively affect the physical health and well-being of people with SMI; however,
      these aspects of health are often neglected. This article identifies ways that
      nurses in all practice settings can use health promotion, assessment and
      treatment to improve the physical health of people with SMI in relation to these
      four areas.

PMID- 28513400
TI  - Role of nurses in supporting patients to self-manage chronic conditions.
AB  - The burden of chronic illness is increasing globally as a result of increased
      life expectancy, unhealthy lifestyles, and advances in medical interventions and
      treatments. Therefore, people living with chronic conditions, and their families,
      will have to assume greater responsibility in managing such conditions. However,
      to do so they require appropriate support from healthcare services. This article
      explores some of the tensions that hinder the self-management of chronic
      conditions. It emphasises the importance of individuals and their families having
      the desire, and being enabled, to assume an active and decisive role in the
      management of chronic conditions. Nurses have a role in enabling patients to
      optimise their self-management skills, but organisational constraints in
      healthcare services, as well as constraints in nurse training and nursing roles,
      may mean that nurses are unable to fulfil this role. This article considers some
      of the factors that may limit the development of patient and nursing roles in
      relation to self-management of chronic conditions.

PMID- 28513401
TI  - Brain natriuretic peptide: what the nurse needs to know.
AB  - Rationale and key points Brain natriuretic peptide is a chemical secreted when
      the heart is under strain. It is sampled by a blood test. This article informs
      nurses about how brain natriuretic peptide can be used as a diagnostic and
      prognostic marker for patients with cardiac conditions. " A brain natriuretic
      peptide level within the normal range in a patient who is not receiving
      treatment, almost certainly rules out a significant cardiac condition. " An
      elevated brain natriuretic peptide level suggests an active cardiac condition and
      further investigations are indicated, usually an electrocardiogram and
      echocardiogram. " A highly elevated brain natriuretic peptide level is a marker
      for a more severe prognosis.

PMID- 28513402
TI  - Safeguarding Adults in Nursing Practice (Second edition) Northway Ruth Jenkins
      Robert Safeguarding Adults in Nursing Practice (Second edition) 240pp L21.99
      Learning Matters/Sage 9781473954847 1473954843 [Formula: see text].
AB  - It is refreshing to find a book that explores nursing practice and adult
      safeguarding in the manner that this one does.

PMID- 28513403
TI  - Spirituality and Coping with Loss: End of Life Healthcare Practice Greenstreet
      Wendy Spirituality and Coping with Loss: End of Life Healthcare Practice 160pp
      L25.99 CRC Press 9781785231483 1785231480 [Formula: see text].
AB  - Sometimes a book that seems at first more concerned with theory than practice can
      turn out to be a fascinating and valuable text for all nurses.

PMID- 28513404
TI  - [A bomb attack in the Netherlands; how would we provide hospital care?]
AB  - - There is an ever-present threat of large-scale incidents and disasters, such as
      terrorism and natural disasters.- Preparation and planning are the key to
      successful response to major incidents and disasters, which is why education,
      training sessions and exercises take place in the Netherlands.- Analysis of
      recent large-scale incidents in Europe and the USA emphasises the importance of
      adequate distribution of the wounded to centres where the correct care can be
      provided.- A major step has been taken in the Netherlands to provide for such an
      eventuality with the introduction of distribution plans for the wounded, and
      other initiatives such as a regional hospital disaster plan.- If a large-scale
      incident should take place the Netherlands also has a Major Incident Hospital at
      its disposal; this is a unique facility that can guarantee availability of 200
      spare beds to the Netherlands healthcare system within 30 minutes.

PMID- 28513405
TI  - [A football player with an evident knee trauma].
AB  - A 22-year-old male presented with medial sided instability of the right knee
      three days after shooting a blocked ball. Physical examination, which is usually
      feasible in the acute phase, showed grade 3 laxity of the superficial medial
      collateral ligament. MRI confirmed a distal rupture, which needs repair within 2
      weeks after onset.

PMID- 28513406
TI  - [The court physician, the clergyman, a learned society and smallpox].
AB  - Variolation was introduced in England in the first half of the 18th century. The
      positive effects of this new method for preventing smallpox were already known in
      the Netherlands around 1720, one of whom was the Dutch physician Boerhaave. In
      spite of this, it took another 30 years before variolation was used in the
      Netherlands. Despite receiving positive advice and information from his learned
      English friends Sloane and Sherard, Boerhaave did not apply nor advise the use of
      variolation. There were various arguments for this restrained approach. In 1754
      Thomas Schwencke found that conditions were favourable for the introduction of
      variolation in The Hague. There was support from the House of Orange-Nassau (the
      current royal family in the Netherlands) and from a learned society; a highly
      motivated clergyman acted as ambassador for the new technique and the court
      physician Schwencke was willing to take the lead. A similar combination had
      previously been effective in England, though the ambassador there was not a
      clergyman but an influential noble lady.

PMID- 28513407
TI  - [Cardiac resynchronization therapy: who is a candidate and who is not?]
AB  - - Cardiac resynchronisation therapy (CRT) is a treatment for patients with
      impaired cardiac pump function (left ventricular ejection fraction <= 35%) and a
      wide QRS complex who, despite maximum tolerated medical therapy, remain
      symptomatic.- In addition to reducing symptoms, CRT can reduce hospital
      admissions and improve survival.- Selection of patients for CRT remains
      difficult. Despite the fact that predicting and influencing success of CRT has
      improved, ~30% of patients do not respond to the therapy.- Optimizing therapy and
      follow-up of patients after implantation requires a multidisciplinary approach
      tailored to the individual patient.- Cardiac rehabilitation with life style
      advices and structured exercise training maximizes patient benefit from CRT.

PMID- 28513408
TI  - [Legally capable care refuser has rights as well as responsibilities].
AB  - It is hard to determine how a doctor should act when a patient with a somatic
      condition refuses medical care. The Dutch law obliges a doctor to inform a
      patient about his condition and the possible treatment options. This includes an
      effort to reach out and make contact with the patient. But how far should a
      doctor's responsibility reach when a patient refuses contact? We point out that
      refusal of medical care can also be seen in the light of a patient's autonomy. We
      thereby propose that falling ill gives responsibilities to a patient too, which
      include making the effort to seek medical care and cooperate with treatment.

PMID- 28513409
TI  - [A woman with acute bilateral vision loss].
AB  - A 46-year-old woman presented to the emergency department with progressive
      bilateral loss of vision followed by headache. She had been taking topiramate 25
      mg daily for eight days before presentation. In the end, she was diagnosed with
      topiramate-induced acute glaucoma for which she received appropriate treatment.

PMID- 28513410
TI  - [What if the sperm donor has a hereditary disease? Informed consent needed for
      sharing medical information].
AB  - There are no regulations in the Netherlands regarding the exchange of important
      genetic information that has become available after the birth of a child
      conceived with donor gametes. This may lead to difficult situations such as when
      the gamete donor is found to suffer from a genetic cancer-predisposition
      disorder. Genetic information about the donor that becomes available later may be
      of great importance to donor offspring. Genetic information uncovered in the
      donor child may likewise be of importance to legal offspring of the gamete donor.
      We propose an informed-consent procedure for both donors and recipients to take
      better care of this issue.

PMID- 28513411
TI  - [Injuries resulting from accidents and violence in the Netherlands; results of an
      Emergency Department register].
AB  - - Injuries from accidents and violence are amongst the most important public
      health issues in the world, including in Europe and the Netherlands.- Using the
      Dutch Injury Surveillance System and the Dutch Burden of Injury Model, we
      describe the incidence and costs associated with injuries in the Netherlands that
      are registered via Emergency Departments (ED). We also map the main causes of
      injury by age category.- Annually, 700,000 patients attend the ED of a hospital
      with an injury; 1 in 6 attendees is admitted.- The societal costs of these
      injuries totals 3.2 billion euro per year. These costs consist of direct care
      related costs and indirect costs through work absence.- Private injuries
      contribute to more than half of the number of casualties. Injuries occur
      relatively more often in children and the elderly.- The key underlying causes
      differ per age category. Common causes in all ages are cycling accidents, falls
      from heights, and other fall-related incidents.- The government should continue
      to deliver the public health interventions for prevention of fall injuries and
      cycling accidents.

PMID- 28513412
TI  - [Multidisciplinary approach of facial injuries].
AB  - BACKGROUND: Approximately one quarter of polytrauma patients has facial injuries,
      which usually lead to loss of form and function. Several specialties are involved
      in the acute and reconstructive phases of facial injuries, such as oral and
      maxillofacial surgery, otorhinolaryngology, plastic surgery, ophthalmology and
      dentistry. CASE DESCRIPTION: A 25-year-old man with severe facial injuries was
      brought to the shock room after sustaining high-energy trauma. He had a panfacial
      fracture that required reconstruction. This was done with two surgeries, with an
      interval of 4 days. The patient recovered successfully after this. CONCLUSION:
      Because of the complexity of facial trauma, many factors are involved in acute
      care and treatment. It is therefore important to designate one coordinating
      specialty to guide this process. The oral and maxillofacial surgeon plays a vital
      role in this.

PMID- 28513413
TI  - [NHG 'Traumatic wounds and bite wounds' treatment guideline].
AB  - - The 'Traumatic wounds and bite wounds' treatment guideline by the NHG (Dutch
      College of General Practitioners) has recommendations for treating traumatic
      wounds, bite wounds and wound infection.- It is important to distinguish between
      traumatic wounds and bite wounds because treatment of lacerations and cuts
      differs from treatment of bites.- Clean a wound under a lukewarm water tap; avoid
      using disinfectants.- Preferably close traumatic wounds within 12 hours, provided
      that the wounds have been carefully cleaned and that there are no referral
      indications. The strict limit of 6 hours has been abandoned because the age of
      the wound does not seem to be related to increased infection risk.- Do not close
      bite wounds unless there is a low estimated risk of infection, it is considered
      cosmetically important, closure is possible within 8 hours, provided that the
      wounds have been carefully cleaned, and there are no referral indications.

PMID- 28513414
TI  - [Prehospital triage in trauma patients; ambulance care and deployment of a mobile
      medical team].
AB  - - The prehospital trauma triage system consisting of regional ambulance services
      and overarching availability of mobile medical teams, the level criteria for
      trauma centres and in-hospital care for trauma patients are well-organised in the
      Netherlands.- However, the quality of prehospital triage in the Netherlands is
      inadequate at the moment, with an average under-triage rate of more than 30%.
      There is, thus, much room for improvement in the quality of prehospital triage.-
      Research in this area is now taking off, partly because of the arrival of a new
      quality indicator from the Netherlands National Health Care Institute, which
      states that at least 90% of multiple-trauma patients should be primarily taken to
      a level 1 trauma centre.

PMID- 28513415
TI  - The Fungal Cell Wall: Structure, Biosynthesis, and Function.
AB  - The molecular composition of the cell wall is critical for the biology and
      ecology of each fungal species. Fungal walls are composed of matrix components
      that are embedded and linked to scaffolds of fibrous load-bearing
      polysaccharides. Most of the major cell wall components of fungal pathogens are
      not represented in humans, other mammals, or plants, and therefore the immune
      systems of animals and plants have evolved to recognize many of the conserved
      elements of fungal walls. For similar reasons the enzymes that assemble fungal
      cell wall components are excellent targets for antifungal chemotherapies and
      fungicides. However, for fungal pathogens, the cell wall is often disguised since
      key signature molecules for immune recognition are sometimes masked by
      immunologically inert molecules. Cell wall damage leads to the activation of
      sophisticated fail-safe mechanisms that shore up and repair walls to avoid
      catastrophic breaching of the integrity of the surface. The frontiers of research
      on fungal cell walls are moving from a descriptive phase defining the underlying
      genes and component parts of fungal walls to more dynamic analyses of how the
      various components are assembled, cross-linked, and modified in response to
      environmental signals. This review therefore discusses recent advances in
      research investigating the composition, synthesis, and regulation of cell walls
      and how the cell wall is targeted by immune recognition systems and the design of
      antifungal diagnostics and therapeutics.

PMID- 28513416
TI  - The Role of ESX-1 in Mycobacterium tuberculosis Pathogenesis.
AB  - In this article, we have described several cellular pathological effects caused
      by the Mycobacterium tuberculosis ESX-1. The effects include induction of
      necrosis, NOD2 signaling, type I interferon production, and autophagy. We then
      attempted to suggest that these pathological effects are mediated by the
      cytosolic access of M. tuberculosis-derived materials as a result of the
      phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity
      of ESAT-6 is most likely due to its pore-forming activity at the membrane. The
      amyloidogenic characteristic of ESAT-6 is reviewed here as a potential mechanism
      of membrane pore formation. In addition to ESAT-6, the ESX-1 substrate EspB
      interferes with membrane-mediated innate immune mechanisms such as efferocytosis
      and autophagy, most likely through its ability to bind phospholipids. Overall,
      the M. tuberculosis ESX-1 secretion system appears to be a specialized system for
      the deployment of host membrane-targeting proteins, whose primary function is to
      interrupt key steps in innate immune mechanisms against pathogens. Inhibitors
      that block the ESX-1 system or block host factors critical for ESX-1 toxicity
      have been identified and should represent attractive potential new
      antituberculosis drugs.

PMID- 28513418
TI  - Flagellar expression in clinical isolates of non-typeable Haemophilus influenzae.
AB  - PURPOSE: Haemophilus influenzae is a commensal organism found in the upper
      respiratory tract of humans. When H. influenzae becomes a pathogen, these
      bacteria can move out of their commensal niche and cause multiple respiratory
      tract diseases such as otitis media, sinusitis, conjunctivitis and bronchitis in
      children, and chronic obstructive pulmonary disease in adults. However, H.
      influenzae is currently considered a non-flagellate bacterium. METHODOLOGY AND
      RESULTS: In this study, 90 clinical isolates of H. influenzae strains (typeable
      and non-typeable) showed different degrees of the swarm-motility phenotype in
      vitro.Keys findings. One of these strains, NTHi BUAP96, showed the highest
      motility rate and its flagella were revealed using transmission electron
      microscopy and Ryu staining. Moreover, the flagellar genes fliC and flgH
      exhibited high homology with those of Actinobacillus pleuropneumoniae,
      Escherichia coli and Shigella flexneri. Furthermore, Western blot analysis, using
      anti-flagellin heterologous antibodies from E. coli, demonstrated cross-reaction
      with a protein present in NTHi BUAP96. CONCLUSION: This study provides, for the
      first time, information on flagellar expression in H. influenzae, representing an
      important finding related to its evolution and pathogenic potential.

PMID- 28513417
TI  - Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV
      infected children in Zimbabwe.
AB  - BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on
      the epidemiology of multidrug-resistant organisms are scarce for Africa,
      especially in HIV-infected individuals who often have frequent contact with
      healthcare. We investigated the prevalence of extended-spectrum beta-lactamase
      producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected
      children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We
      recruited children who were stable on antiretroviral therapy (ART) attending a
      HIV clinic from August 2014 to June 2015. Information was collected on antibiotic
      use and hospitalization. Stool was tested for ESBL-E through combination disc
      diffusion. API20E identification and antimicrobial susceptibility was performed
      on the positive samples followed by whole genome sequencing. RESULTS: Stool was
      collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range
      (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were
      found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to
      amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6
      % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es
      variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage
      were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year
      (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently
      hospitalized for a chest infection. CONCLUSION: We found a 13.7 % prevalence of
      ESBL-E carriage in a population where ESBL-E carriage has not been described
      previously. Antimicrobial resistance (AMR) in Africa merits further study,
      particularly given the high HIV prevalence and limited diagnostic and therapeutic
      options available.

PMID- 28513419
TI  - Histological findings in severe Mycoplasma pneumoniae pneumonia.

PMID- 28513422
TI  - 2017 Trauma Association of Canada Annual Scientific Meeting Abstracts.

PMID- 28513423
TI  - Bethune Roundtable 2017 Abstracts.

PMID- 28513421
TI  - Clinical and bacteriological characteristics associated with clustering of
      multidrug-resistant tuberculosis.
AB  - SETTING: The impact of the genetic characteristics of Mycobacterium tuberculosis
      on the clustering of multidrug-resistant tuberculosis (MDR-TB) has not been
      analyzed together with clinical and demographic characteristics. OBJECTIVE: To
      determine factors associated with genotypic clustering of MDR-TB in a community
      based study. DESIGN: We measured the proportion of clustered cases among MDR-TB
      patients and determined the impact of clinical and demographic characteristics
      and that of three M. tuberculosis genetic characteristics: lineage, drug
      resistance-associated mutations, and rpoA and rpoC compensatory mutations.
      RESULTS: Of 174 patients from California and Texas included in the study, the
      number infected by East-Asian, Euro-American, Indo-Oceanic and East-African
      Indian M. tuberculosis lineages were respectively 70 (40.2%), 69 (39.7%), 33
      (19.0%) and 2 (1.1%). The most common mutations associated with isoniazid and
      rifampin resistance were respectively katG S315T and rpoB S531L. Potential
      compensatory mutations in rpoA and rpoC were found in 35 isolates (20.1%).
      Hispanic ethnicity (OR 26.50, 95%CI 3.73-386.80), infection with an East-Asian M.
      tuberculosis lineage (OR 30.00, 95%CI 4.20-462.40) and rpoB mutation S531L (OR
      4.03, 95%CI 1.05-23.10) were independent factors associated with genotypic
      clustering. CONCLUSION: Among the bacterial factors studied, East-Asian lineage
      and rpoB S531L mutation were independently associated with genotypic clustering,
      suggesting that bacterial factors have an impact on the ability of M.
      tuberculosis to cause secondary cases.

PMID- 28513424
TI  - A review of six methods for monitoring infliximab concentrations and antibodies
      to infliximab?.
AB  - Anti-TNF-alpha therapy, such as infliximab (IFX), has profoundly changed
      treatment to induce and maintain remission for inflammatory bowel diseases
      patients who do not respond to conventional therapies. Unfortunately, IFX, as a
      chimeric protein, is potentially immunogenic, and antibodies to infliximab (ATI)
      may interfere with the pharmacodynamics and pharmacokinetics of the drug, thus
      resulting in a loss of response for a substantial proportion of patients. The
      clinical efficacy of IFX is correlated with the levels of IFX and ATI. Therefore,
      monitoring patients for the trough levels of IFX and the presence of ATI is very
      important. The procedures and characteristics of six assays for monitoring IFX
      and ATI are described in this review, and the comparisons between them are also
      discussed. To date, there has been no optimal assay for monitoring IFX and ATI.
      Therefore, many technical problems need to be solved to make therapeutic drug and
      immunogenicity monitoring a part of routine clinical management.?.

PMID- 28513425
TI  - Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a
      simulated OTC environment?.
AB  - OBJECTIVE: Evaluate adherence of US consumers to proposed label directions for a
      new 400 mg ibuprofen formulation. METHODS: In this single-arm, open-label,
      multicenter, 30-day study simulating an over-the-counter (OTC)-like environment,
      US analgesic consumers reviewed proposed product packaging for a new 400 mg
      ibuprofen formulation and made a purchase decision. Purchasers used the product
      as needed and recorded use over 30 days. Outcomes included the percentage of
      participants who exhibited correct or acceptable product use for the primary
      endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary
      endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to
      the labeled dosing interval of 6 - 8 hours. Primary endpoint success was met if
      the lower bound of the 95% confidence interval (CI) was >= 85%. RESULTS: Of 685
      purchasers providing use data, correct or acceptable use behavior occurred in
      95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI:
      81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most
      participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%).
      Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~
      82% re-dosed between the 4- and 6-hour time intervals. Adverse events were
      consistent with prior ibuprofen 200 mg experience. CONCLUSION: This study
      provides evidence that a majority of US consumers would be able to use OTC
      ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse
      rates were low and unlikely to generate an excess risk of clinically important
      adverse events.?.

PMID- 28513426
TI  - Pharmacokinetics and bioequivalence of a pregabalin 150-mg capsule in healthy
      Thai subjects.
AB  - OBJECTIVE: The purpose of the study was to evaluate the pharmacokinetics and
      bioequivalence of pregabalin following administration of a 150-mg capsule of test
      and reference products. METHOD: The study was designed as a randomized, two
      treatment, two-period, two-sequence, single-dose crossover with 1-week washout
      period between period I and period II dosing. 20 healthy male and female Thai
      subjects were enrolled in the study. Each subject was in fasted state for ~ 10
      hours prior to receiving a single oral 150-mg pregabalin capsule. Serial blood
      samples were collected at pre-dose until 32 hours after drug administration.
      Plasma samples were extracted by protein precipitation and derivatized with 4
      chloro-7-nitrobenzofurazan. Pregabalin plasma concentrations were determined by
      HPLC method, and pharmacokinetic parameters were calculated. For bioequivalence
      assessment, the differences of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0
      inf</sub> means based on ln-transformed data were assessed by the 90% confidence
      interval (CI). RESULTS: Pharmacokinetic parameters were determined that test and
      reference products showed 0.96 +/- 0.35 and 1.04 +/- 0.96 hours for
      t<sub>max</sub>, 4,594.217 +/- 834.195 and 4,568.68 +/- 573.963 ng/mL for
      C<sub>max</sub>, 30,048.150 +/- 2,998.920 and 29,315.722 +/- 2,747.396 ng*h/mL
      for AUC<sub>0-t</sub>, 30,594.210 +/- 2,872.317 and 29,831.454 +/- 2,688.020
      ng*h/mL for AUC<sub>0-inf</sub>, respectively. The 90% CIs of C<sub>max</sub>,
      AUC<sub>0-t</sub>, and AUC<sub>0-inf</sub> for test and reference products were
      assessed at 95.356 - 104.630%, 99.303 - 105.751%, and 99.373 - 105.788%,
      respectively. The results were within the acceptance criteria of 80 - 125%.
      CONCLUSION: Pharmacokinetic parameters of a single oral 150-mg pregabalin capsule
      in healthy Thai subjects were evaluated and showed rapid absorption. 90% CI for
      the differences of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-inf</sub>
      were within the acceptable range of the criteria so that bioequivalence of the
      test and reference products of pregabalin 150-mg capsule could be concluded.?.

PMID- 28513427
TI  - Population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1
      receptor agonist (recombinant exendin-4, rE-4) in Chinese patients with type 2
      diabetes mellitus?.
AB  - OBJECTIVE: To investigate the population pharmacokinetics of lyophilized
      recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients
      with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and
      individualized treatment. METHODS: Twelve patients with T2DM were enrolled to
      receive subcutaneous injections of rE-4 at 5 ug twice daily for 84 days.
      Administration dosage was adjusted from 5 ug to 10 ug twice daily at day 29 in
      case of glycated albumin (GA) >= 17%. The population pharmacokinetic model was
      developed in the nonlinear mixed-effects modeling software NONMEM. RESULTS: The
      data were best described by a two-compartment model with first-order absorption
      and elimination. The outcome parameters were as follows: apparent clearance
      (CL/F) 6.67 L/h, apparent distribution volume of central compartment
      (V<sub>c</sub>/F) 19.4 L, absorption rate constant (K<sub>a</sub>) 1.39 h<sup>
      1</sup>, apparent distribution volume of peripheral compartment (V<sub>p</sub>/F)
      22.6 L, intercompartmental clearance (Q/F) 1.28 L/h. The interindividual
      variabilities for CL/F, V<sub>c</sub>/F, K<sub>a</sub>, and Q/F were 64.4%,
      57.7%, 45.5%, and 153.3%, respectively. The intra-individual variability of
      proportional error model was 41.7%. No covariate was screened out that showed
      significant influence on the model parameters. CONCLUSIONS: The established two
      compartment model with first-order absorption and elimination successfully
      described the pharmacokinetic characteristics of rE-4 in Chinese patients with
      T2DM.?.

PMID- 28513429
TI  - Five-year publication rate of podium presentations at SICOT Annual Conference: an
      observational study and new objective proposal of conference power.
AB  - INTRODUCTION: The SICOT Conference Committee continually tries to improve the
      quality of presentations at their annual international meetings. However to the
      author's best knowledge, no previous study has been undertaken to determine
      abstract quality. This study aimed to determine the five-year publication rate of
      presentations made at the 2009 SICOT Annual International Conference (AIC),
      recognise predictors of full-text publication, identify inconsistencies between
      presentations and publications, and determine presentation-publication delay.
      METHODS: We retrieved all 329 oral presentation abstracts from the 2009 SICOT
      Conference, recorded fundamental study details and conducted a comprehensive,
      electronic search of Medline and PubMed to determine publication status. For
      subsequent publications, we examined for inconsistencies between presentation
      abstracts and full-text publications, whether there were retrospectively
      identifiable publication predictors and calculated presentation-publication
      delay. RESULTS: The five-year publication rate for all presentations was 31.3%,
      for oral presentations. The average presentation-publication delay was 23.4
      months. Observational studies were the most commonly published studies.
      Publications most commonly resulted from studies related to hip and knee
      subspecialties. CONCLUSION: Our study shows that almost one third of all
      abstracts presented at SICOT led to a full-text publication. This is a positive
      outcome particularly when made in comparison to similar studies of other
      reputable international conferences such as European Federation of Orthopaedics
      and Traumatology (EFORT) and American Academy of Orthopaedic Surgeons (AAOS).
      This study re-enforces SICOT's reputation as a world leading international
      conference with a strict peer-review process yielding high-quality presentations.

PMID- 28513430
TI  - Global clues to the nature of genomic mutations in humans.
AB  - An analysis of worldwide human genetic variation reveals the footprints of
      ancient changes in genomic mutation processes.

PMID- 28513428
TI  - Slipped capital femoral epiphysis: a review of management in the hip impingement
      era.
AB  - Slipped capital femoral epiphysis (SCFE) remains the most common adolescent hip
      disorder. Most cases present with stable slips, and in situ fixation is the most
      commonly adopted treatment worldwide. The introduction of the concept of
      femoroacetabular impingement and subsequent studies have revealed SCFE-related
      hip impingement to be a significant pre-arthritic condition, and the previously
      suggested remodeling of the proximal femur after in situ fixation has been called
      into question. Complex proximal femoral osteotomies and more recently intra
      articular procedures via surgical hip dislocation have been employed. The
      literature is still lacking a strong evidence to undertake such aggressive
      procedures. Moreover, the application of a particular procedure regarding the
      nature of the slip, being stable or unstable, the degree of the slip, and the
      condition of the physis has not been extensively described in the literature. The
      purpose of this article is to outline the SCFE-related hip impingement, to review
      the best evidence for the current treatment options for both stable and unstable
      slips, and to develop an algorithm for decision making.

PMID- 28513432
TI  - Keeping carbon dioxide in check.
AB  - The response of the brainstem to increased levels of carbon dioxide in the blood
      is coordinated with the response of the cardiovascular system.

PMID- 28513431
TI  - Dissection of zebrafish shha function using site-specific targeting with a Cre
      dependent genetic switch.
AB  - Despite the extensive use of zebrafish as a model organism in developmental
      biology and regeneration research, genetic techniques enabling conditional
      analysis of gene function are limited. In this study, we generated Zwitch, a Cre
      dependent invertible gene-trap cassette, enabling the establishment of
      conditional alleles in zebrafish by generating intronic insertions via in vivo
      homologous recombination. To demonstrate the utility of Zwitch, we generated a
      conditional sonic hedgehog a (shha) allele. Homozygous shha mutants developed
      normally; however, shha mutant embryos globally expressing Cre exhibited strong
      reductions in endogenous shha and shha target gene mRNA levels and developmental
      defects associated with null shha mutations. Analyzing a conditional shha mutant
      generated using an epicardium-specific inducible Cre driver revealed unique roles
      for epicardium-derived Shha in myocardial proliferation during heart development
      and regeneration. Zwitch will extend the utility of zebrafish in organ
      development and regeneration research and might be applicable to other model
      organisms.

PMID- 28513433
TI  - Distributing tasks via multiple input pathways increases cellular survival in
      stress.
AB  - Improving in one aspect of a task can undermine performance in another, but how
      such opposing demands play out in single cells and impact on fitness is mostly
      unknown. Here we study budding yeast in dynamic environments of hyperosmotic
      stress and show how the corresponding signalling network increases cellular
      survival both by assigning the requirements of high response speed and high
      response accuracy to two separate input pathways and by having these pathways
      interact to converge on Hog1, a p38 MAP kinase. Cells with only the less
      accurate, reflex-like pathway are fitter in sudden stress, whereas cells with
      only the slow, more accurate pathway are fitter in increasing but fluctuating
      stress. Our results demonstrate that cellular signalling is vulnerable to trade
      offs in performance, but that these trade-offs can be mitigated by assigning the
      opposing tasks to different signalling subnetworks. Such division of labour could
      function broadly within cellular signal transduction.

PMID- 28513436
TI  - Drowning: a silent killer.

PMID- 28513437
TI  - UK air pollution and public health.

PMID- 28513439
TI  - Offline: The message of mental health.

PMID- 28513434
TI  - A unifying mechanism for the biogenesis of membrane proteins co-operatively
      integrated by the Sec and Tat pathways.
AB  - The majority of multi-spanning membrane proteins are co-translationally inserted
      into the bilayer by the Sec pathway. An important subset of membrane proteins
      have globular, cofactor-containing extracytoplasmic domains requiring the dual
      action of the co-translational Sec and post-translational Tat pathways for
      integration. Here, we identify further unexplored families of membrane proteins
      that are dual Sec-Tat-targeted. We establish that a predicted heme-molybdenum
      cofactor-containing protein, and a complex polyferredoxin, each require the
      concerted action of two translocases for their assembly. We determine that the
      mechanism of handover from Sec to Tat pathway requires the relatively low
      hydrophobicity of the Tat-dependent transmembrane domain. This, coupled with the
      presence of C-terminal positive charges, results in abortive insertion of this
      transmembrane domain by the Sec pathway and its subsequent release at the
      cytoplasmic side of the membrane. Together, our data points to a simple unifying
      mechanism governing the assembly of dual targeted membrane proteins.

PMID- 28513438
TI  - Improving access to biosimilars in low-income countries.

PMID- 28513435
TI  - A bioactive peptide amidating enzyme is required for ciliogenesis.
AB  - The pathways controlling cilium biogenesis in different cell types have not been
      fully elucidated. We recently identified peptidylglycine alpha-amidating
      monooxygenase (PAM), an enzyme required for generating amidated bioactive
      signaling peptides, in Chlamydomonas and mammalian cilia. Here, we show that PAM
      is required for the normal assembly of motile and primary cilia in Chlamydomonas,
      planaria and mice. Chlamydomonas PAM knockdown lines failed to assemble cilia
      beyond the transition zone, had abnormal Golgi architecture and altered levels of
      cilia assembly components. Decreased PAM gene expression reduced motile ciliary
      density on the ventral surface of planaria and resulted in the appearance of
      cytosolic axonemes lacking a ciliary membrane. The architecture of primary cilia
      on neuroepithelial cells in Pam-/- mouse embryos was also aberrant. Our data
      suggest that PAM activity and alterations in post-Golgi trafficking contribute to
      the observed ciliogenesis defects and provide an unanticipated, highly conserved
      link between PAM, amidation and ciliary assembly.

PMID- 28513440
TI  - Luca Richeldi: high hopes for rare lung diseases.

PMID- 28513441
TI  - The art of transplantation: Mend the Living.

PMID- 28513442
TI  - Digitising the mind.

PMID- 28513443
TI  - Health economics.

PMID- 28513444
TI  - Essential medicines for universal health coverage.

PMID- 28513445
TI  - Health economics - Authors' reply.

PMID- 28513446
TI  - Health economics.

PMID- 28513447
TI  - Essential medicines for universal health coverage - Authors' reply.

PMID- 28513448
TI  - Child poverty: no future?

PMID- 28513449
TI  - No psychotherapy monoculture for anxiety disorders.

PMID- 28513451
TI  - Department of Error.

PMID- 28513450
TI  - No psychotherapy monoculture for anxiety disorders - Authors' reply.

PMID- 28513452
TI  - Department of Error.

PMID- 28513453
TI  - Chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) kills more than 3 million people
      worldwide every year. Despite progress in the treatment of symptoms and
      prevention of acute exacerbations, few advances have been made to ameliorate
      disease progression or affect mortality. A better understanding of the complex
      disease mechanisms resulting in COPD is needed. Smoking cessation programmes,
      increasing physical activity, and early detection and treatment of comorbidities
      are further key components to reduce the burden of the disease. However, without
      a global political and economic effort to reduce tobacco use, to regulate
      environmental exposure, and to find alternatives to the massive use of biomass
      fuel, COPD will remain a major health-care problem for decades to come.

PMID- 28513454
TI  - Lysosomal dysfunction in neurodegenerative diseases.
AB  - Dane literaturowe z ostatnich lat jednoznacznie wskazuja na udzial lizosomow w
      programowanej smierci komorki. Dysfunkcje lizosomow uposledzaja fuzje
      autofagosomow z lizosomami, co prowadzi do wakuolizacji cytoplazmy. Obecnosc
      wakuoli autofagalnych obladowanych uszkodzonymi organellami i nieprawidlowymi
      bialkami jest cecha charakterystyczna wielu chorob neurodegeneracyjnych.
      Agregacja niezdegradowanego materialu zaburza homeostaze komorki powodujac smierc
      neuronu w wyniku apoptozy i/lub nekrozy. Ponadto indukowany kalpainami lub
      spowodowany mutacjami rozpad blony lizosomu uwalnia katepsyny, ktore indukuja
      szlak smierci komorki. W artykule przedstawiono mechanizm smierci komorki
      nerwowej, laczacy zaburzenie szlaku autofagalno-lizosomalnego z dysfunkcjami
      lizosomow, zwany lizosomalnym szlakiem smierci neuronu.

PMID- 28513455
TI  - Glucose tolerance disorders during treatment with glucocorticoids in patients
      with inflammatory diseases of the musculoskeletal system - based on the analysis
      of data from the literature and own research results.
AB  - Glucocorticoids are among the most frequently used anti-inflammatory and
      immunosuppressive drugs. They are widely used in the treatment of numerous
      autoimmune disorders. However, the treatment with glucocorticoids is connected
      with the risk of a number of side effects. Among them, glucose tolerance
      disorders play an important role. The results of meta-analyses show that the risk
      of diabetes is from 1.4 to 2.5 times higher in the case of treated patients in
      comparison to the general population. Glucocorticoids can directly impair
      pancreatic beta-cell secretion. Nevertheless, a crucial role in the hyperglycemic
      activity seems to be played by a peripheral glucose uptake reduction, principally
      in the skeletal muscle, which is responsible for the decrease of insulin
      sensitivity, and can manifest itself in the increase of postprandial blood
      glucose levels. If they are used in higher doses and for a prolonged period, they
      can also reduce the inhibitory effect of insulin on hepatic glucose production,
      which can lead to an increase of fasting plasma glucose. Numerous literature data
      indicate that in the case of patients who suffer from inflammatory diseases of
      the musculoskeletal system, the treatment with low to moderate doses of
      glucocorticoids, for a short period, does not significantly increase the
      metabolic risk. The beneficial role in this area may be connected with an anti
      inflammatory and immunosuppressive effect. The regular assessment of the
      postprandial glucose, especially in the afternoon and evening, has the highest
      diagnostic sensitivity of glucocorticoid-induced glucose tolerance disorders. In
      the case of patients without a prior diagnosis of diabetes, after discontinuation
      of treatment, the oral glucose tolerance test should be considered in order to
      identify the presence of persistent disorders.

PMID- 28513456
TI  - Aflatoxins: characteristics and impact on human health.
AB  - Some molds commonly occurring in the natural environment produce mycotoxins in
      the process of secondary metabolism. Aspergillus flavus and A. parasiticus are
      species of molds, which are responsible for the production of aflatoxins and are
      crucial in the pathogenesis of human diseases. Aspergillus species present in
      decaying plants, the soil and their spores are transferred via air currents and
      insects to crops and food storages. Aflatoxins B1, B2, G1, G2, M1 and M2 are the
      most common derivatives of aflatoxins. Ingestion of contaminated food is the main
      source of exposure to aflatoxins, which adversely affect the health of both
      humans and animals. The compounds can cause acute or chronic toxic effects of a
      teratogenic, mutagenic, carcinogenic, immunotoxic or hepatotoxic character.
      Molecular aflatoxins affect DNA mutations, postranslation peptids chains
      modification, proteins and nucleic acids methylation and the formation of free
      radicals. Due to aflatoxins carcinogenic features and frequent occurrence in food
      and forages they are routinely examinated in some groceries and agricultural
      products.

PMID- 28513457
TI  - Bacteriocins from lactic acid bacteria as an alternative to antibiotics.
AB  - Bacteriocins are ribosomally synthesized, proteinaceous substances that inhibit
      the growth of closely related species through numerous mechanisms. The
      classification system used in this review divided bacteriocins into four sub
      groups based on their size. Currently, there is extensive research focused on
      bacteriocins and their usage as a food preservative. The increasing incidence of
      multidrug resistant bacterial pathogens is one of the most pressing medical
      problems in recent years. Recently, the potential clinical application of LAB
      (Lactic Acid Bacteria) bacteriocin has been the subject of investigations by many
      scientists. Bacteriocins can be considered in a sense as antibiotic, although
      they differ from conventional antibiotics in numerous aspects. The gene-encoded
      nature of bacteriocins makes them easily amenable through bioengineering to
      either increase their activity or specify target microorganism. Owing to this
      feature of bacteriocins, antibiotic therapy would become less damaging to the
      natural gut microflora, which is a common drawback of conventional antibiotic
      use. Bacteriocins from lactic acid bacteria represent one of the most studied
      microbial defense systems and the idea of subjecting them to bioengineering to
      either increase antimicrobial activity or further specify their target
      microorganism is now a rapidly expanding field. This review aimed to present
      bacteriocins as a possible alternative to conventional antibiotics basic on
      latest scientific data.

PMID- 28513458
TI  - Cofilin - a protein controlling dynamics of actin filaments.
AB  - Cofilins are evolutionary conserved proteins present in all Eukaryotic cells.
      Their primary function is dynamic reorganization of actin cytoskeleton. Two
      cofilin isoforms are known: cofilin 1, present in all studied non-muscle cells
      and in embryonic muscle cells, and cofilin 2, which dominates in mature skeletal
      and cardiac muscles. Polypeptide chains of both isoforms fold into a structure
      homological to a conservative ADF (actin depolymerizing factor) domain, which is
      characteristic of actin depolymerizing factor. In cofilin molecule two actin
      binding sites were found. One site binds monomeric and filamentous actin, the
      second one interacts only with the filament. Binding of cofilin to actin filament
      causes a change in the orientation of subunits, which results in filament
      severing. This increases number of ends which can either elongate or shorten the
      filament, depending on the conditions. Cofilin interactions with monomeric actin
      decreases availability of polymerization-competent actin subunits. Cofilin
      activity is controlled by phosphorylation, binding membrane phospholipids, local
      pH and oxidative stress. Under conditions of oxidative stress oxidation of
      cysteine residues leads to formation of dimers, which are able to cross-link
      actin filaments. Stable actin-cofilin rods save cellular ATP, which is not used
      during active polymerization process. This facilitates faster cell recovery from
      the stress. The final cellular reaction on the environmental stimuli is a
      resultant of cofilin activity and activities of other actin-binding proteins,
      which function either synergistically or antagonistically. Due to the central
      role in the regulation of actin filaments dynamics, cofilin is involved in
      development of cancer, neurodegenerative diseases, congenital myopathies and
      cardiomyopathies.

PMID- 28513459
TI  - Effects of Granulocyte Colony-Stimulating Factor on Opsonin Receptor Expression
      and Neutrophil Antibacterial Activity in a Mouse Model of Severe Acute
      Pancreatitis.
AB  - The antimicrobial function of neutrophils, which is dependent on opsonin
      receptors, deteriorates in severe acute pancreatitis (SAP). Granulocyte colony
      stimulating factor (G-CSF) putatively enhanced levels of the opsonin receptors
      CD11b and CD32/16 in healthy human subjects, and provided protection against
      infection in animal models of SAP. A statistically convincing study of the effect
      of G-CSF on CD32/16 expression in an SAP model is lacking. We used a mouse model
      of SAP to investigate the association between G-CSF administration and CD32/16
      levels on neutrophils and bacterial translocation. G-CSF or saline was
      subcutaneously injected into SAP-induced mice. The pancreases were histologically
      examined, and leukocytes were stained to count neutrophils. The expression of
      CD11b and CD32/16 on neutrophils was measured by flow cytometry, and bacterial
      translocation was observed by bacterial culture. The numbers of CD11b and CD32/16
      positive neutrophils were significantly elevated in the SAP mice treated with G
      CSF, and the mean fluorescence intensities of these receptors on neutrophils were
      significantly elevated. Bacterial translocations to cavity organs were suppressed
      from 17% to 6% by G-CSF treatment. Our results indicated that the number of
      neutrophils significantly increased with increasing expression of CD11b and
      CD32/16 and their mean fluorescence intensities (MFIs). This inhibited bacterial
      translocation to other organs. These results are in accord with other studies in
      SAP dogs and SAP mice. Our findings suggest that G-CSF was effective in
      protecting against bacterial infection in SAP mice.

PMID- 28513460
TI  - The role of oxidative stress in female infertility and in vitro fertilization.
AB  - Infertility problem involves many couples of reproductive age. It has been
      estimated that in Poland 0.7-1.0 million pairs require treatment, while for more
      than half of them assisted reproduction is the only recommended and effective
      method. Infertility affects 13 to 15% of the world's population. A major concern
      is the age-related decline in female fertility even more that often a decision
      about pregnancy is taken at later age. Recent studies show that increased
      production of reactive oxygen species is an important factor in etiopathogenesis
      of pregnancy and affects female reproduction. It was found that oxidative stress
      may damage the oocytes and may impair their fertilization capacity. Oxidative
      stress may also lead to embryo fragmentation and formation of numerous
      developmental abnormalities, and is regarded to be one of the important reasons
      of spontaneous and recurrent miscarriage. Moreover, overproduction of reactive
      oxygen species has a significant impact on the success of in vitro fertilization
      (IVF).

PMID- 28513461
TI  - The importance of Bordetella pertussis strains which do not produce virulence
      factors in the epidemiology of pertussis.
AB  - Bordetella pertussis strains, which have lost the ability to produce antigens,
      such as pertactin - Prn, pertussis toxin - Ptx, filamentous haemagglutinin - FHA,
      fimbriae type 2 and 3 - Fim 2 and 3, tracheal colonization factor - TcfA, have
      recently been isolated in countries with a high vaccination coverage. The
      emergence of such isolates might have resulted from B. pertussis natural
      evolution course or adaptive mechanisms, allowing increased circulation of the
      pathogen in vaccinated populations. So far, the majority of described mutants
      were deficient in the Prn production. Prn deficient isolates were found in
      countries which use acellular pertussis vaccines (aP) in routine immunization
      programmes. The increase of frequency of Prn- strains isolation was correlated
      with the period of routine vaccination with aP vaccines. In most countries, the
      spread of these isolates has resulted from independent mutations rather than from
      the expansion of a single clone. Prn- isolates were collected from patients
      showing typical clinical symptoms of pertussis found for Prn+ strains. Results of
      in vitro and in vivo studies have shown that Prn-, Ptx- and FHA- isolates retain
      cytotoxic properties, and besides Ptx- isolates, were lethal in intranasally
      infected mice. Further explanation of the impact of antigen deficiencies on
      virulence and transmission of B. pertussis in the context of the continuous
      increase of pertussis incidence is necessary to develop a new, optimized strategy
      of pertussis prevention.

PMID- 28513462
TI  - Invasion and metastasis of tumour cells resistant to chemotherapy.
AB  - Metastatic tumours resistant to chemotherapy are the major cause of the clinical
      failure in the treatment of malignant diseases. It is observed often that drugs
      active against primary tumours do not exhibit the same efficacy towards
      metastatic tumour cells having modified signaling pathways. Among cellular
      factors involved in the development of the metastatic potential of multidrug
      resistant tumour cells are some oncoproteins, antiapoptotic proteins, mutated
      suppressor proteins, integrins and CD44 receptor. It was also demonstrated that
      numerous chemotherapeutics have the effect on the emergence of the metastatic
      potential and multidrug resistance (MDR) phenomenon of tumour cells. The results
      of numerous studies suggest that genes involved in the development of MDR and
      metastatic phenotype of tumour cells are regulated by the same signaling
      pathways. They lead to the activation of transcription factors e.g. HIF-1alpha,
      NF-kappaB, Ets1 and AP-1 controlling the expression of genes involved in the
      development of the metastatic potential of multidrug resistant tumour cells. The
      identification of key cellular factors responsible for the emergence of the
      metastatic potential of MDR tumour cells could lead to the development of new
      efficient strategies for the treatment of metastatic tumours resistant to the
      conventional chemotherapy.

PMID- 28513463
TI  - Alzheimer's disease against peptides products of enzymatic cleavage APP protein:
      Biological, pathobiological and physico-chemical properties of fibrillating
      peptides.
AB  - Various peptides products of enzymatic cleavage of key for Alzheimer's disease
      Amyloid Precursor Protein (APP) are well known, but still are matter of
      scientific debate. The Abeta type products are especially challenging for
      experimental and medical research. This paper outlines several, still poorly
      known, biological and medical processes such as peptides biology, i.e.,
      formation, biodistribution, translocation, transport and finally removal from
      brain compartments and body fluids like Intracellular Fluid (ICF), Cerebrospinal
      Fluid (CSF), Interstitial Fluid (ISF), blood serum or urine. In addition, the
      following studies concerning AD patients might prove challenging and
      simultaneously promising: peptides translocation through Blood-Brain - Barrier
      (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB) and their removal from the
      brain according to a new concept of glymphatic system; - diagnostic difficulties
      that stem from physico-chemical properties and the nature of proteins or
      fibrillating peptides itself like low concentration, short half-live and from
      experimental-technical problems as well like high adsorption or low solubility of
      Abeta, tau or amylin. The study of diagnostic parameters is very important, as it
      may better reflect early changes before the disease develops; one such parameter
      is the Abeta42/Abeta40 ratio, or the ratio with the total tau concentration
      combination and other new biomarkers like Abeta1-38; other factors include
      oxidative stress and inflammation process proteins, complement factor H, alpha-2
      macroglobulin, or clusterin. The study of various forms of pathological amyloid
      deposits that emerge in different but specific brain regions AD patients seems to
      be crucial as well. The composition of the first initial pathological, pre
      fibrillating monomers of fibrillating peptides and their role in AD development
      and disease progression have been described as well. They are even more
      challenging for science and simultaneously might be more promising in early
      diagnosis for AD patients. As always in science, research leads to endless
      discoveries and further inquiry. Fundamental problems in this field most probably
      are still far from being definitively comprehended, and multiple crucial
      questions await better answers. What we really need is to study more and deeper
      into this matter.

PMID- 28513464
TI  - Pharmacological features of osthole.
AB  - Coumarins are a group of naturally occurring compounds common in the plant world.
      These substances and their derivatives exhibit a broad range of biological
      activities. One of the naturally occurring coumarins is osthole, which can most
      frequently be found in plants of the Apiaceae family. Cnidium monnieri (L.)
      Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.). It has
      anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic
      properties; apart from that, inhibition of platelet aggregation has also been
      proved. The impact of osthole on bone metabolism has been demonstrated; also its
      hepatoprotective and neuroprotective properties have been confirmed. The
      inhibitory effect of this metokcompound on the development of neurodegenerative
      diseases has been proved in experimental models. Anticancer features of osthole
      have been also demonstrated both in vitro on different cell lines, and in vivo
      using animals xenografts. Osthole inhibited proliferation, motility and
      invasiveness of tumor cells, which may be associated with the induction of
      apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti
      cancer mode of action has not been fully elucidated. A synergistic effect of
      osthole with other anti-tumor substances has been also reported. Modification of
      its chemical structure led to the synthesis of many derivatives with significant
      anticancer effects. To sum up, osthole is an interesting therapeutic option, due
      to both its direct effect on tumor cells, as well as its neuroprotective or anti
      inflammatory properties. Thus, there is a chance to use osthole or its synthetic
      derivatives in the treatment of cancer.

PMID- 28513466
TI  - Non-small cell lung cancer - mutations, targeted and combination therapy.
AB  - Year after year, a growing number of cases of non-small cell lung cancer (NSCLC),
      mostly caused by smoking, have been noted. Most patients die because of the late
      detection of cancer and tumor resistance to treatment with cytostatics. Treatment
      of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to
      cytostatic agents and the co-existence of many diseases, which substrate is, like
      lung cancer, cigarette smoking. Along with the development of molecular biology,
      targeted therapy has started to be used, affecting specific signaling pathways
      involved in the processes of oncogenesis. Compounds that inhibit the activity of
      receptor tyrosine kinases are very well examined and already used in clinical
      practice. NSCLC is characterized by multiple mutations, including EGFR (epidermal
      growth factor receptor) and KRAS. Rarer but clinically significant is the
      rearrangement of the ALK gene. Currently, for NSCLC treatment a number of EGFR
      inhibitors such as erlotinib, gefitinib, afatinib and two compounds targeted in
      ALK kinase crizotinib and ceritinib are applied. Unfortunately, despite numerous
      studies, we are still not able to improve the treatment effectiveness of patients
      with KRAS mutations. The most efficient solution would be to use a combination of
      the compounds exhibiting synergistic effects on tumor cells. The literature data
      describes numerous examples of the combination treatment of NSCLC cells. Some
      combinations of compounds are already in clinical trials. Most attempts relate to
      tyrosine kinase inhibitors in combination with other types of pharmacologic
      inhibitor or immunotherapy. This paper describes the mutations occurring in NSCLC
      and drugs used in clinical practice as well as being in preclinical development.

PMID- 28513465
TI  - The role of SRSF1 in cancer.
AB  - SRSF1 jest wielofunkcyjnym bialkiem bioracym udzial w procesach zwiazanych z
      metabolizmem RNA. Nastepstwem zaburzen ekspresji SRSF1, obserwowanych w wielu
      typach nowotworow, sa nieprawidlowosci w skladaniu pre-mRNA, zmiany stabilnosci
      transkryptow i poziomu translacji onkogenow oraz genow supresorowych. Regulujac
      roznicowe skladanie transkryptow genow CCND1, RAC1, KLF6, BCL2L1, MCL1 oraz
      CASP9, SRSF1 indukuje zmiany w cyklu komorkowym, proliferacji i apoptozie.
      Czynnik SRSF1 wplywa takze na angiogeneze nowotworowa i przerzutowanie, m.in.
      promujac powstawanie proangiogennych wariantow VEGF oraz wariantu splicingowego
      genu RON, ktory aktywuje proces przejscia nablonkowo-mezenchymalnego. Ze wzgledu
      na istotna role SRSF1 w rozwoju i progresji nowotworow, bialko to jest
      obiecujacym celem terapii przeciwnowotworowych wykorzystujacych zwiazki hamujace
      jego aktywnosc. W artykule przedstawiono najnowsze informacje o wplywie SRSF1 na
      nowotworzenie oraz jego potencjalne znaczenie w opracowaniu nowych strategii w
      leczeniu chorych z nowotworami.

PMID- 28513467
TI  - Evolution of the Fermi surface of BiTeCl with pressure.
AB  - We report measurements of Shubnikov-de Haas oscillations in the giant Rashba
      semiconductor BiTeCl under applied pressures up to  ~2.5 GPa. We observe two
      distinct oscillation frequencies, corresponding to the Rashba-split inner and
      outer Fermi surfaces. BiTeCl has a conduction band bottom that is split into two
      sub-bands due to the strong Rashba coupling, resulting in two spin-polarized
      conduction bands as well as a Dirac point. Our results suggest that the chemical
      potential lies above this Dirac point, giving rise to two Fermi surfaces. We use
      a simple two-band model to understand the pressure dependence of our sample
      parameters. Comparing our results on BiTeCl to previous results on BiTeI, we
      observe similar trends in both the chemical potential and the Rashba splitting
      with pressure.

PMID- 28513468
TI  - Structural evolution during calcination and sintering of a (La0.6Sr0.4)0.99CoO3
      delta nanofiber prepared by electrospinning.
AB  - Design of three-dimensional metal oxide nanofibers by electrospinning is being
      widely explored. However, the impacts of calcination and sintering on the
      resulting morphology remain unknown. For the first time, (La0.6Sr0.4)0.99CoO3
      delta (LSC) nanofiber, which is among the most promising electrode materials for
      solid oxide fuel cells, was synthesized by sol-gel electrospinning. By elevating
      the temperature in oxygen using in situ transmission electron microscopy, we
      discovered the structural transitions from nanofibers to nanotubes and then to
      nano-pearl strings. This facile and up-scalable method can be widely applied to
      design metal oxide one-dimensional nanomaterials with precise control in both
      geometry (nanofiber, nanotube and nano-pearl string) and surface area (by varying
      grain size).

PMID- 28513469
TI  - Amplified excited state intramolecular proton transfer fluorescence of butterfly
      shaped bis-2,6-dibenzothiazolylphenol.
AB  - A butterfly-shaped benzothiazole derivative, bis-2,6-dibenzothiazolylphenol (2),
      was synthesized via 4-methylene bridging two 2,6-dibenzothiazolylphenol (1)
      molecules, and the excited-state intramolecular proton transfer (ESIPT)
      fluorescence of 1 and 2 were comparably investigated by steady-state
      spectroscopic experiments with the aid of theoretical simulations for structure
      and energy. It was found that 2 showed similar ESIPT emissions to those of 1 in
      solution and solid states, but the ESIPT fluorescence quantum yield was
      substantially amplified in the case of the more 'integrated' 2. In both
      tetrahydrofuran (THF) and CHCl3 solvents, ESIPT occurred and orange emissions at
      580-590 nm from keto tautomers were observed, where the absolute fluorescence
      quantum yield was measured to be 0.28 and 0.41 for 1, as well as 0.41 and 0.59
      for 2, respectively. In the solid state, 2 showed an ESIPT emission at 570 nm
      with an absolute fluorescence quantum yield of 0.38, which is substantially
      shorter and larger than the corresponding values of 1 (592 nm and 0.26)
      respectively. Furthermore, both 2 and 1 showed strongly blue-shifted green
      emissions around 520 nm from the deprotonated anion species in N,N-dimethyl
      formamide (DMF). A similar blue-shifted green emission was also found with the
      addition of fluoride in the THF solution of 2 or 1, suggesting that the
      competitive deprotonation makes the ESIPT impossible.

PMID- 28513470
TI  - Phase diagram of the Shastry-Sutherland Kondo lattice model with classical
      localized spins: a variational calculation study.
AB  - We study the Shastry-Sutherland Kondo lattice model with additional
      Dzyaloshinskii-Moriya (DM) interactions, exploring the possible magnetic phases
      in its multi-dimensional parameter space. Treating the local moments as classical
      spins and using a variational ansatz, we identify the parameter ranges over which
      various common magnetic orderings are potentially stabilized. Our results reveal
      that the competing interactions result in a heightened susceptibility towards a
      wide range of spin configurations including longitudinal ferromagnetic and
      antiferromagnetic order, coplanar flux configurations and most interestingly,
      multiple non-coplanar configurations including a novel canted-flux state as the
      different Hamiltonian parameters like electron density, interaction strengths and
      degree of frustration are varied. The non-coplanar and non-collinear magnetic
      ordering of localized spins behave like emergent electromagnetic fields and drive
      unusual transport and electronic phenomena.

PMID- 28513471
TI  - Dual-functional aniline-assisted wet-chemical synthesis of bismuth telluride
      nanoplatelets and their thermoelectric performance.
AB  - The wet-chemical approach is of great significance for the synthesis of two
      dimensional (2D) bismuth telluride nanoplatelets as a potential thermoelectric
      (TE) material. Herein, we proposed a simple and effective solution method with
      the assistance of aniline for the fabrication of bismuth telluride nanoplatelets
      at a low temperature of 100  degrees C. The choice of aniline with its dual
      function avoided the simultaneous use of a capping regent and a toxic reductant.
      The as-synthesized nanoplatelets have a large size of more than 900 * 500 nm2 and
      a small thickness of 15.4 nm. The growth of bismuth telluride nanoplatelets are
      related to the Bi/Te ratio of precursors indicating that a larger content of the
      Bi precursor is more conducive to the formation of 2D nanoplatelets. The bismuth
      telluride nanoplatelets pressed into a pellet show a smaller electrical
      resistivity (~6.5 * 10-3 Omega . m) and a larger Seebeck coefficient (-135 MUV K
      1), as well as a lower thermal conductivity (0.27 W m-1 K-1) than those of
      nanoparticles. The next goal is to further reduce the electrical resistivity and
      optimize the TE performance by disposing of the residual reactant of aniline
      adsorbed on the surface of the nanoplatelets.

PMID- 28513472
TI  - Experimental and numerical studies of beetle-inspired flapping wing in hovering
      flight.
AB  - In this paper, we measure unsteady forces and visualize 3D vortices around a
      beetle-like flapping wing model in hovering flight by experiment and numerical
      simulation. The measurement of unsteady forces and flow patterns around the wing
      were conducted using a dynamically scaled wing model in the mineral-oil tank. The
      wing kinematics were directly derived from the experiment of a real beetle. The
      3D flow structures of the flapping wing were captured by using air bubble
      visualization while forces were measured by a sensor attached at the wing base.
      In comparison, the size and topology of spiral leading edge vortex, trailing edge
      vortex and tip vortex are well matched from experimental and numerical studies.
      In addition, the time history of forces calculated from numerical simulation is
      also similar to that from theforce measurement. A difference of average force is
      in order of 10 percent. The results indicate that the leading edge vortex due to
      rotational acceleration at the end of the stroke during flapping wing causes
      significant reduction of lift. The present study provides useful information on
      hover flight to develop a beetle-like flapping wing Micro Air Vehicle.

PMID- 28513473
TI  - A density functional approach to ferrogels.
AB  - Ferrogels consist of magnetic colloidal particles embedded in an elastic polymer
      matrix. As a consequence, their structural and rheological properties are
      governed by a competition between magnetic particle-particle interactions and
      mechanical matrix elasticity. Typically, the particles are permanently fixed
      within the matrix, which makes them distinguishable by their positions. Over
      time, particle neighbors do not change due to the fixation by the matrix. Here we
      present a classical density functional approach for such ferrogels. We map the
      elastic matrix-induced interactions between neighboring colloidal particles
      distinguishable by their positions onto effective pairwise interactions between
      indistinguishable particles similar to a 'pairwise pseudopotential'. Using Monte
      Carlo computer simulations, we demonstrate for one-dimensional dipole-spring
      models of ferrogels that this mapping is justified. We then use the
      pseudopotential as an input into classical density functional theory of
      inhomogeneous fluids and predict the bulk elastic modulus of the ferrogel under
      various conditions. In addition, we propose the use of an 'external
      pseudopotential' when one switches from the viewpoint of a one-dimensional dipole
      spring object to a one-dimensional chain embedded in an infinitely extended bulk
      matrix. Our mapping approach paves the way to describe various inhomogeneous
      situations of ferrogels using classical density functional concepts of
      inhomogeneous fluids.

PMID- 28513474
TI  - Dielectric analysis based on spherical-shell model for cationic and anionic
      spherical polyelectrolyte brushes.
AB  - We report here a dielectric study on cationic and anionic spherical
      polyelectrolyte brush (SPB) (consisting of a polystyrene (PS) core and poly (2
      aminoethylmethacrylate hydrochloride (PAEMH) chains or poly (acrylic acid) (PAA)
      chains grafted onto the core) suspensions over a frequency range of 40 Hz-110
      MHz. The relaxation behavior of the suspensions shows significant changes in the
      brush layer properties when changing the particle mass fraction or pH of the
      system. After eliminating the electrode polarization effect at a low frequency,
      two definite relaxations related to interfacial polarization, around 100 kHz and
      10 MHz respectively, are observed. Based on a single layer spherical-shell model,
      we developed a curve-fitting procedure to analyze such dielectric spectra for
      soft particles, and then calculated the dielectric properties of the components
      of the SPBs (such as the permittivities and conductivities of the layer and
      solution phase), especially the layer thickness d s of the polyelectrolyte chain
      (PE) layer. We also found a larger confinement degree of counterions in the PAEMH
      brush due to the protonation of the amino group. Moreover, the repulsive force
      between the SPB particles is evaluated by using the d s combined with the
      relative theoretical formulas. We conclude that by raising (reducing) the acidity
      of the system, the stability of the PAEMH-SPB (PAA-SPB) suspension was improved.
      An increase in particle concentration can also improve the stability of these two
      dispersions.

PMID- 28513475
TI  - Self-assembling graphene-anthraquinone-2-sulphonate supramolecular nanostructures
      with enhanced energy density for supercapacitors.
AB  - Boosting the energy density of capacitive energy storage devices remains a
      crucial issue for facilitating applications. Herein, we report a graphene
      anthraquinone supramolecular nanostructure by self-assembly for supercapacitors.
      The sulfonated anthraquinone exhibits high water solubility, a pi-conjugated
      structure and redox active features, which not only serve as a spacer to interact
      with and stabilize graphene but also introduce extra pseudocapacitance
      contributions. The formed nest-like three-dimensional (3D) nanostructure with
      further hydrothermal treatment enhances the accessibility of ion transfer and
      exposes the redox-active quinone groups in the electrolytes. A fabricated all
      solid-state flexible symmetric device delivers a high specific capacitance of
      398.5 F g-1 at 1 A g-1 (1.5 times higher than graphene), superior energy density
      (52.24 Wh kg-1 at about 1 kW kg-1) and good stability (82% capacitance retention
      after 10 000 cycles).

PMID- 28513476
TI  - The influence of magnetic order on the magnetoresistance anisotropy of Fe1 +
      delta-x Cu x Te.
AB  - We performed resistance measurements on [Formula: see text]Cu x Te with [Formula:
      see text] in the presence of in-plane applied magnetic fields, revealing a
      resistance anisotropy that can be induced at a temperature far below the
      structural and magnetic zero-field transition temperatures. The observed
      resistance anisotropy strongly depends on the field orientation with respect to
      the crystallographic axes, as well as on the field-cooling history. Our results
      imply a correlation between the observed features and the low-temperature
      magnetic order. Hysteresis in the angle-dependence indicates a strong pinning of
      the magnetic order within a temperature range that varies with the Cu content.
      The resistance anisotropy vanishes at different temperatures depending on whether
      an external magnetic field or a remnant field is present: the closing temperature
      is higher in the presence of an external field. For [Formula: see text] the
      resistance anisotropy closes above the structural transition, at the same
      temperature at which the zero-field short-range magnetic order disappears and the
      sample becomes paramagnetic. Thus we suggest that under an external magnetic
      field the resistance anisotropy mirrors the magnetic order parameter. We discuss
      similarities to nematic order observed in other iron pnictide materials.

PMID- 28513477
TI  - Microtube array membrane bioreactor promotes neuronal differentiation and
      orientation.
AB  - An important challenge in neuronal tissue engineering is to create innovative
      tools capable of promoting cellular response in terms of neuronal differentiation
      and neurite orientation that may be used as investigational platforms for
      studying neurobiological events and neurodegenerative disorders. A novel membrane
      bioreactor was created to provide a 3D well-controlled microenvironment for
      neuronal outgrowth. The bioreactor consisted of poly-L-lactic acid highly aligned
      microtube array (PLLA-MTA) membranes assembled in parallel within a chamber that
      establish an intraluminal and an extraluminal compartment whose communication
      occurs through the pores of the MTA membrane walls. The bioreactor configuration
      provided a wide surface area for cell adhesion in a small volume, and offered a
      peculiar arrangement that directed neuronal orientation. The combination of an
      appropriate membrane porosity, pore interconnectivity and very thin walls ensured
      optimal indirect perfusion to cell compartment, and enhanced the mass transfer of
      metabolites and catabolites protecting neurons from shear stress. The PLLA-MTA
      membrane bioreactor promoted the growth and differentiation of SH-SY5Y cells
      toward a neuronal phenotype, and guided neurite alignment giving rise to a 3D
      neuronal tissue-like construct. It provides an innovative platform to study
      neurobiological phenomena in vitro and by guiding neuronal orientation for repair
      and/or regeneration.

PMID- 28513478
TI  - A gaze independent hybrid-BCI based on visual spatial attention.
AB  - OBJECTIVE: Brain-computer interfaces (BCI) use measures of brain activity to
      convey a user's intent without the need for muscle movement. Hybrid designs,
      which use multiple measures of brain activity, have been shown to increase the
      accuracy of BCIs, including those based on EEG signals reflecting covert
      attention. Our study examined whether incorporating a measure of the P3 response
      improved the performance of a previously reported attention-based BCI design that
      incorporates measures of steady-state visual evoked potentials (SSVEP) and alpha
      band modulations. APPROACH: Subjects viewed stimuli consisting of two bi
      laterally located flashing white boxes on a black background. Streams of letters
      were presented sequentially within the boxes, in random order. Subjects were cued
      to attend to one of the boxes without moving their eyes, and they were tasked
      with counting the number of target-letters that appeared within. P3 components
      evoked by target appearance, SSVEPs evoked by the flashing boxes, and power in
      the alpha band are modulated by covert attention, and the modulations can be used
      to classify trials as left-attended or right-attended. MAIN RESULTS: We showed
      that classification accuracy was improved by including a P3 feature along with
      the SSVEP and alpha features (the inclusion of a P3 feature lead to a 9% increase
      in accuracy compared to the use of SSVEP and Alpha features alone). We also
      showed that the design improves the robustness of BCI performance to individual
      subject differences. SIGNIFICANCE: These results demonstrate that incorporating
      multiple neurophysiological indices of covert attention can improve performance
      in a gaze-independent BCI.

PMID- 28513479
TI  - Producing lasting amphiphobic building surfaces with self-cleaning properties.
AB  - Nowadays, producing building surfaces that prevent water and oil uptake and which
      present self-cleaning activity is still a challenge. In this study, amphiphobic
      (superhydrophobic and oleophobic) building surfaces were successfully produced. A
      simple and low-cost process was developed, which is applicable to large-scale
      building surfaces, according the following procedure: (1) by spraying a SiO2
      nanocomposite which produces a closely-packed nanoparticle uniform topography;
      (2) by functionalizing the previous coating with a fluorinated alkoxysilane,
      producing high hydrophobicity and oleophobicity. The formation of a Cassie-Baxter
      regime, in which air pockets could be trapped between the aggregates of
      particles, was confirmed by topographic study. The building surface demonstrated
      an excellent self-cleaning performance. Finally, the surface presented lasting
      superhydrophobicity with high stability against successive attachment/detachment
      force cycles. This high durability can be explained by the effective grafting of
      the silica nanocomposite coating skeleton with the substrate, and with the
      additional fluorinated coating produced by condensation reactions.

PMID- 28513480
TI  - Highly sensitive and scalable AAO-based nano-fibre SERS substrate for sensing
      application.
AB  - Well-ordered periodic nanostructures are excellent substrates for many surface
      enhanced Raman spectroscopy (SERS) applications. Conventional fabrication
      approaches such as high precision electron beam lithography or focused ion beam
      produce high resolution nano-features with great reproducibility at the expense
      of low throughput. In this work, a highly sensitive and scalable AAO-nano-fibre
      (ANF) SERS substrate is demonstrated by optimising the second anodisation time of
      the standard two-step anodisation of aluminium and performing an additional wet
      etching step on the resulting AAO substrate. The optimised ANF substrate exhibits
      SERS sensitivity that surpasses the AAO nanoholes and the metal-film-on
      nanoparticles substrates. A detection limit of 0.1 nM is achieved with a signal
      to-noise ratio of 2.6-3 using a low excitation power of 0.1 mW. The ANF substrate
      exhibits an enhancement factor of 9.28 * 106 and a standard deviation of no more
      than 8%. The results indicate that the highly sensitive and scalable ANF
      substrate is a promising substrate for commercial SERS application.

PMID- 28513481
TI  - Recurrent painful lesions on the lower lip.

PMID- 28513482
TI  - Trichosporon inkin causing subcutaneous sinus tract: Successfully treated by oral
      and ultrasound-guided intralesional itraconazole therapy.

PMID- 28513484
TI  - Bilateral subungual epidermoid inclusions of big toes.

PMID- 28513483
TI  - A case of dermatomyositis with underlying unusual malignancy.

PMID- 28513485
TI  - Acantholysis or the Auspitz sign? A revelation of the life of Carl Heinrich
      Auspitz.

PMID- 28513486
TI  - Pegylated liposomal doxorubicin-induced miliaria crystallina and lichenoid
      follicular eruption.

PMID- 28513487
TI  - Every ending is a new beginning.

PMID- 28513488
TI  - Imaging in tuberculosis-associated uveitis.
AB  - Intraocular tuberculosis (TB) can have several clinical presentations, affecting
      nearly every tissue of the eye. These clinical signs have specific imaging
      characteristics which help in associating them with tuberculous etiology. This
      review enumerates the conventional and emerging imaging techniques for
      intraocular TB and highlights their clinical application for diagnosis and
      management of specific clinical presentations.

PMID- 28513489
TI  - The influence of corneal collagen cross-linking on anterior chamber in
      keratoconus.
AB  - AIMS: This study aimed to evaluate the effect of the corneal changes following
      corneal cross-linking (CXL) on the anterior chamber in keratoconus patients.
      MATERIALS AND METHODS: Forty-five eyes of 32 patients who had been diagnosed with
      progressive keratoconus and had undergone CXL were included in this retrospective
      study. The thinnest corneal thickness of the progressive keratoconus patients
      included in the study was >400 MU. The preoperative (T0), postoperative 6th month
      (T1), and postoperative 1st year (T2) anterior chamber volume (ACV), anterior
      chamber angle (ACA), and anterior chamber depth (ACD) scheimpflug imaging values
      were obtained for each eye. RESULTS: The mean T0 ACV value was 182.79 +/- 36.68
      mmwhile the T1 value was 201.25 +/- 41.73 mm3 and the T2 value was 208.40 +/-
      42.69 mm3 with a statistically significant difference between the periods (P =
      0.001). The mean T0 ACA value was 38.64 degrees  +/-5.85 degrees , increasing to
      41.45 degrees  +/-4.83 degrees  in the T1 and 42.10 degrees  +/- 4.84 degrees  in
      the T2. The T0 value was significantly lower than the post-CXL values (P =
      0.003). The mean ACD value was 3.73 +/- 0.29 mm at the T0 and 3.82 +/- 0.38 mm at
      the T1 and 3.84 +/- 0.36 mm at the T2. The pre-CXL values were significantly
      lower than the post-CXL values (P = 0.001). CONCLUSIONS: The improvement of
      corneal parameters by CXL in keratoconus patients can have a positive effect on
      anterior chamber parameters as well. This effect becomes marked at the
      postoperative first 6-month evaluation.

PMID- 28513490
TI  - Coexistence of herpes simplex virus infection in microsporidial stromal keratitis
      associated with granulomatous inflammation.
AB  - BACKGROUND: Microsporidial stromal keratitis poses several diagnostic challenges.
      Patients may present with corneal ulceration, marked stromal thinning, or even as
      a quite corneal scar. The presentation of microsporidial stromal keratitis
      commonly mimics viral keratitis. Microbiology scrapings are usually helpful;
      however, scraping and culture-negative cases pose a significant diagnostic
      dilemma. Histopathological examination is diagnostic but shows varying degree of
      inflammation, predominantly composed of polymorphonuclear leukocytes.
      Granulomatous inflammation, in microsporidial stromal keratitis, is never well
      described, and the authors in this article aim to describe the presence of
      granulomatous inflammation in microsporidial stromal keratitis, in patients with
      associated herpes simplex virus (HSV) keratitis. METHODS: This was a
      retrospective and observational study conducted at a tertiary eye care center.
      RESULTS: Of 263 patients who underwent therapeutic penetrating keratoplasty for
      infectious keratitis, during 2011-2013, seven patients were diagnosed as
      microsporidial stromal keratitis. Microsporidial spores could be demonstrated on
      microbiological scrapings in 5/7 (71%) of cases, but identified on
      histopathological examination and also confirmed on polymerase chain reaction
      (PCR) for microsporidium in 100% of cases. There was evidence of diffuse stromal
      necrosis with markedly severe degree of polymorphonuclear leukocytic infiltrates,
      with granulomatous inflammation in 42% of cases. Interestingly, these were
      positive for HSV-1 DNA on PCR. Review of medical records revealed much severe
      clinical presentations in patients with granulomatous inflammation, in comparison
      to cases without granulomatous inflammation. CONCLUSIONS: The authors hereby
      recommend that severe clinical presentation in patients with microsporidial
      stromal keratitis, markedly dense polymorphonuclear leukocytic infiltrates or the
      presence of granulomatous inflammation on the histopathological examination,
      should be investigated further for the presence of HSV-1 DNA for better patient
      management and good visual outcome.

PMID- 28513491
TI  - Results of a new "mirror tuck technique" for fixation of lacrimal bypass tube in
      conjunctivodacryocystorhinostomy.
AB  - CONTEXT: Conjunctivodacryocystorhinostomy (CDCR) is the procedure of choice for
      proximal canalicular blocks. However, the complications of tube migration and
      extrusion limit its widespread practice. AIM: The aim of this study is to
      evaluate the efficacy and complications of the new "mirror tuck technique" for
      fixation of lacrimal bypass glass tube without holes in proximal canalicular
      blocks in laser CDCR. MATERIALS AND METHODS: A prospective interventional study
      was conducted in forty consecutive eyes of adult patients, undergoing 980 nm
      diode laser CDCR for proximal canalicular blocks. After creating the tract under
      endoscopic guidance, the collar of the glass tube was fixed to the conjunctiva
      with 6-0 prolene suture by "mirror tuck technique." Success was defined as the
      absence of extrusion of tube with patent tract and relief in epiphora at 1 year
      of follow-up. RESULTS: Both anatomical and functional success was achieved in 39
      (97.5%) cases. Tube displacement occurred in one patient suffering from allergic
      conjunctivitis in which the tube had to be removed. A temporary heaviness was
      reported by 5 (12.5%) patients till about 2 weeks. Conjunctival overgrowth over
      the tube occurred in 1 (2.5%) eye at 5 months which was excised and treated with
      application of 0.02% mitomycin C with no subsequent recurrence. There were no
      cases of suture abscess or suture intolerance warranting tube removal.
      CONCLUSION: "Mirror tuck technique" is an effective method for tube fixation (for
      tube without holes) in CDCR. However, it is important to position the
      conjunctival opening so as to leave sufficient space for passage of sutures for
      anchorage medially.

PMID- 28513492
TI  - Repeatability and agreement of five imaging systems for measuring anterior
      segment parameters in healthy eyes.
AB  - PURPOSE: The purpose of this study is to assess the repeatability and agreement
      of five imaging devices, namely, the Pentacam (Oculus), Sirius (CSO), Orbscan IIz
      (Bausch and Lomb), Corvis (Oculus), and ultrasound pachymetry (UP, Tomey) in
      measuring steep keratometry (sKm), flat keratometry (fKm), central corneal
      thickness (CCT), thinnest corneal thickness (TCT), and anterior chamber depth
      (ACD) in healthy individuals. DESIGN: This was prospective, comparative study.
      SUBJECTS: Forty-six healthy Indian patients. MATERIALS AND METHODS: Forty-six
      eyes of 46 healthy participants underwent three consecutive scans on each device
      by a single examiner. Within-subject standard deviation, test-retest
      repeatability (TRT), and coefficient of variation (COV) for assessing
      repeatability and Bland-Altman plots for the agreement between the mean
      measurements of each machine were analyzed. MAIN OUTCOME MEASURES: The
      repeatability and agreement between the five devices for the measurements of sKm,
      fKm, CCT, TCT, and ACD. RESULTS: The TRT of sKm measurements ranged between 0.23
      diopter (D) (with Pentacam) and 0.83 D (with Orbscan). The same of fKm, TCT, ACD,
      and CCT measurements ranged between 0.28 D (with Pentacam) and 0.74 D (with
      Sirius), 7.78 MUm (Sirius) and 19.81 MUm (Orbscan), 0.05 mm (Orbscan) and 0.07
      (Sirius), and 7.36 MUm (Sirius) and 18.02 MUm (Orbscan), respectively. The TRT of
      sKm and fKm measurements with Pentacam was significantly lower than those with
      Orbscan and Sirius. The TRT of TCT measurement with Sirius was significantly
      lower than that with Pentacam (4.53 MUm) and Orbscan (7.15 MUm). There were
      statistically significant differences in the mean measurements of all parameters
      between the devices. The 95% limit of agreement on the Bland-Altman analysis was
      wide for the measurement pairs with all the devices. Significant proportional
      bias in the agreement was detected for TCT measurements with all the device pairs
      and for the ACD measurements between Sirius and Pentacam. CONCLUSIONS: The
      repeatability estimates of sKm, fKm, TCT, ACD, and CCT measurements with
      Pentacam, Orbscan, Sirius, Corvis, and UP in Indian eyes were good. However, the
      differences in the measurements between the devices were statistically
      significant and the same cannot be used interchangeably for anterior segments
      measurements.

PMID- 28513493
TI  - Inflammatory choroidal neovascularization in Indian eyes: Etiology, clinical
      features, and outcomes to anti-vascular endothelial growth factor.
AB  - BACKGROUND AND OBJECTIVES: The aim was to study the clinical profile of
      inflammatory choroidal neovascularization (CNV) and its treatment response to
      intravitreal bevacizumab or ranibizumab on pro re nata (PRN) basis in Indian
      eyes. MATERIALS AND METHODS: This was a retrospective case series of consecutive
      patients with inflammatory CNV treated with anti-vascular endothelial growth
      factor (anti-VEGF) in a tertiary eye care center in Eastern India between 2009
      and 2014. The data about clinical features, investigations, treatment, and
      outcomes were obtained from the medical records. We included patients with active
      inflammatory CNV but with no evidence of inflammation and were treated with anti
      VEGF alone, with a minimum follow-up of 6 months. Main outcome measures were a
      clinical and etiological profile of inflammatory CNV in Indian eyes and their
      response to treatment. RESULTS: Thirty eyes of 28 patients were included in the
      study. The mean follow-up was 17.93 +/- 14.28 months (range 6-53 months). In our
      cohort, seven (23.33%) eyes had inflammatory CNV secondary to idiopathic
      choroiditis, four (13.33%) eyes had toxoplasmosis, idiopathic panuveitis, and
      Vogt Koyanaki Harada's disease each. Three (10%) eyes had geographic helicoid
      peripapillary choroidopathy and tubercular choroiditis each. Remaining two
      (6.66%) eyes had punctate inner choroidopathy, while multifocal choroiditis with
      panuveitis, resolved endogenous endophthalmitis and Hansen's diseases were the
      etiology in one (3.33%) case of inflammatory CNV each. The mean number of
      injections were 2.76 (range 1-5). Among thirty eyes of inflammatory CNV, 16
      (53.3%) eyes showed improvement, eight (26.6%) maintained the same vision,
      whereas six (20%) eyes showed deterioration of vision. Interpretations and
      Conclusion: Idiopathic choroiditis was the most common cause of inflammatory CNV
      and PRN intravitreal anti-VEGF (ranibizumab or bevacizumab) appears to have
      effective treatment response.

PMID- 28513494
TI  - Tear film and ocular surface dysfunction in diabetes mellitus in an Indian
      population.
AB  - PURPOSE: Ophthalmic complications in diabetes such as retinopathy, cataract, and
      infections have been extensively studied. Recently, attention has been drawn
      toward ocular surface changes in diabetes mellitus (DM). This study has been
      carried out to investigate the tear film and ocular surface abnormalities in type
      II DM patients. MATERIALS AND METHODS: A total of 83 participants (130 eyes) were
      enrolled: 53 diabetics (80 eyes) and 30 healthy controls (50 eyes). Of the 53
      diabetics, 24 patients (42 eyes) had some diabetic retinopathy. The tear film and
      ocular surface were evaluated using Schirmer test, tear film break-up time
      (TBUT), keratoepitheliopathy score (KES), Rose Bengal Staining (RBS) test, and
      conjunctival impression cytology. RESULTS: When compared with the healthy
      controls, diabetics showed significantly reduced Schirmer, TBUT measurements and
      the higher grades of KES and RBS test (P < 0.001). Impression cytology analysis
      showed goblet cell loss and conjunctival squamous metaplasia in diabetics.
      CONCLUSION: Tear film abnormality is a significant feature of diabetic ocular
      surface diseases. These abnormalities are likely on account of poor quality and
      function of tears, combined with the subnormal ocular surface. Therefore, all
      diabetic patients especially those with evidence of retinopathy changes should
      undergo routine early examination and follow-up of tear function and ocular
      surface parameters.

PMID- 28513495
TI  - Effect of post crosslinking haze on the repeatability of Scheimpflug-based and
      slit-scanning imaging devices.
AB  - PURPOSE: The aim of this study was to analyze the effect of postcollagen
      crosslinking (CXL) haze on the measurement and repeatability of pachymetry and
      mean keratometry (Km) of four corneal topographers. MATERIALS AND METHODS: Sixty
      eyes of sixty patients with progressive keratoconus who had undergone accelerated
      CXL (ACXL) underwent imaging with a scanning slit imaging device (Orbscan II) and
      three Scheimpflug imaging devices (Pentacam HR, Sirius, and Galilei). Post-ACXL
      haze was measured using the densitometry software on the Pentacam HR. Readings of
      the thinnest corneal thickness (TCT) and Km from three scans of each device were
      analyzed. Effect of haze on the repeatability of TCT and Km measurements was
      evaluated using regression models. Repeatability was assessed by coefficient of
      variation. RESULTS: Corneal densitometry in different zones affected the
      repeatability of TCT measurement of Orbscan (P < 0.05) significantly but not the
      repeatability of TCT with Pentacam HR and Sirius (P = 0.03 and 0.05,
      respectively). Km values were affected by haze when measured with the Pentacam HR
      (P < 0.05). The repeatability of Km readings for all devices was unaffected by
      haze. In the anterior 0-2 mm and 2-6 mm zone, TCT (P = 0.43 and 0.45,
      respectively), Km values (P = 0.4 and 0.6, respectively), repeatability of TCT (P
      = 0.1 in both zones), and Km (P = 0.5 and 0.1, respectively) with Galilei were
      found to be the most reliable. CONCLUSION: Galilei measurements appear to be
      least affected by post-ACXL haze when compared with other devices. Hence,
      topography measurements in the presence of haze need to be interpreted with
      caution.

PMID- 28513496
TI  - Intra-arterial chemotherapy for retinoblastoma: Two-year results from tertiary
      eye-care center in India.
AB  - AIM: The aim of this study is to describe treatment outcomes and complications of
      selective intra-arterial chemotherapy (IAC) for intraocular retinoblastoma (RB).
      MATERIALS AND METHODS: A retrospective, interventional series of 10 eyes with RB
      which underwent IAC using melphalan (5 mg/7.5 mg) and topotecan (1 mg), or
      melphalan (5 mg/7.5 mg) alone. Treatment outcomes were evaluated in terms of
      tumor control, vitreous seeds (VS) and subretinal seeds (SRS) control, and globe
      salvage rates. RESULTS: Ten eyes of 10 patients underwent 38 IAC sessions (mean =
      3.8; median = 4; range = 3-5 sessions). Following IAC, complete regression of
      main tumor was seen in 9 eyes (90%) and partial regression in 1 (10%). All four
      eyes with SRS showed complete regression (100%). Of 5 eyes with VS, 3 eyes (60%)
      showed complete regression, 1 eye (20%) showed relapse, while 1 eye (20%) showed
      no response. Globe salvage was achieved in 8 of 10 eyes (80%). Complications
      included transient ophthalmic artery narrowing (n = 2), branched retinal vein
      occlusion (n = 1), forehead skin pigmentation (n = 1), and vitreous hemorrhage (n
      = 2). There was no case of stroke, hemiplegia, metastasis, or death. Transient
      hematological changes included relative pancytopenia (n = 4), relative leukopenia
      (n = 5), and relative thrombocytopenia (n = 4). Mean follow-up was 26 months
      (median = 28, range = 13-36) from the initiation of first IAC. CONCLUSIONS: IAC
      is an effective therapy for globe preservation in eyes with intraocular RB, in
      the setting of a developing country like India. Larger studies with longer follow
      up are required to validate these results.

PMID- 28513497
TI  - Sialadenitis following blepharoplasty: An unusual sequelae.

PMID- 28513498
TI  - Combination of phototherapeutic keratectomy and wavefront-guided photorefractive
      keratectomy for the treatment of Thiel-Behnke corneal dystrophy.
AB  - Phototherapeutic keratectomy (PTK) has been used to treat anterior corneal
      dystrophy but may cause hyperopic shift or corneal high-order aberration. We
      describe the successful treatment of a case of a 43-year-old female with Thiel
      Behnke corneal dystrophy, using PTK followed by wavefront-guided photorefractive
      keratectomy (PRK). The patient had high corneal aberration and hyperopic shift
      after PTK in both eyes. The corneal surface regularity index and surface
      asymmetric index increased after PTK and decreased after wavefront-guided PRK.
      Vision improved from preoperative 20/400 and 20/60 to postoperative 20/20 and
      20/25 in the right eye and the left eye, respectively. Additional wavefront
      guided PRK may enhance the effects of PTK by reducing irregular corneal surfaces
      and by correcting PTK-induced hyperopic shift.

PMID- 28513499
TI  - Role of mini-scleral lens in mucous membrane pemphigoid.
AB  - This study aims to report the use of mini-scleral contact lens in the management
      of mucous membrane pemphigoid (MMP) with persistent epithelial defects. A 68-year
      old male with a history of ocular pain and declining visual acuity was referred
      to our clinic with a diagnosis of MMP. His corrected distance visual acuity
      (CDVA) was 20/200 in the right eye and 20/100 in the left eye. Despite being on
      lubricants, topical steroids and intravenous cyclophosphamide, the patient
      developed persistent corneal epithelial defects in both eyes. He was then given a
      trial of mini-scleral lenses. Within 4 weeks, corneal epithelial defects healed,
      and at 6 months, the CDVA had improved to 20/50 in the right eye and 20/40 in the
      left eye. By improving the corneal surface integrity and visual function, mini
      scleral lenses can play a role in the visual rehabilitation of patients with MMP.

PMID- 28513500
TI  - Rescue vitrectomy with blocked artery massage and bloodletting for branch retinal
      artery occlusion.
AB  - A 61-year-old male suffered from sudden blurred vision and superior visual field
      defect oculus dexter. His vision was counting fingers at 20 cm. Fundoscopy
      demonstrated inferior pale retina and a large embolus located at the proximal
      inferior retinal artery. Branch retinal artery occlusion (BRAO) was diagnosed.
      Initial paracentesis, topical brimonidine tartrate, oral pentoxifylline, and
      hyperbaric oxygen therapy were performed but showed limited improvement. Hence,
      he received 25-gauge vitrectomy, artificial posterior vitreous detachment,
      blocked retinal artery massage, and bloodletting 5 days after onset. After the
      surgery, his vision improved to 20/25. Fundoscopy showed reperfused retina, and
      optical coherence tomography revealed resolved retinal edema. RAO is an
      ophthalmological emergency; however, no standard guideline is available.
      Vitrectomy with blocked retinal artery massage and bloodletting showed favorable
      results in this case of BRAO with a large embolus. More prospective clinical
      trials are needed for setting up the standard treatment.

PMID- 28513501
TI  - Ocular surface burn secondary to smart phone battery blast.

PMID- 28513502
TI  - Comment on: To assess survival outcomes of combined femtosecond laser-assisted
      cataract surgery with 25-gauge vitrectomy surgery at a tertiary eye care center.

PMID- 28513503
TI  - Authors' reply.

PMID- 28513504
TI  - Fundus findings in a case of Joubert syndrome.

PMID- 28513505
TI  - Practice of trabeculectomy by ophthalmologists in Nigeria.
AB  - AIM: To assess the practice of trabeculectomy among ophthalmologists in Nigeria.
      MATERIALS AND METHODS: This was a cross-sectional study in which structured, self
      administered questionnaires were distributed to 80 consenting ophthalmologists
      present during the 2010 annual scientific session of the Ophthalmological Society
      of Nigeria. All consenting ophthalmologists treat glaucoma patients. Information
      obtained were demographic characteristics, glaucoma outpatient load, number of
      trabeculectomies performed in the preceding 1 year and during residency training,
      and factors influencing trabeculectomy practice. Data were analyzed with
      Statistical Package for Social Science version 16.0. Relationships between
      variables were tested using the *2 test for statistical significance. RESULTS:
      Sixty-five of the 80 consenting ophthalmologists responded to the questionnaires
      (81.3% response rate); 32 (53.3%) were females and 28 (46.7%) were males (5 non
      responders). Ages ranged from 30 to 60 years with a mean of 44 years +/- SD 7.7.
      Only 36 (57.1%) performed trabeculectomy in the 1 year preceding the study. There
      was an overall trabeculectomy rate of 0.9/ophthalmologist/month. Of the 15
      respondents who performed more than 15 trabeculectomies during residency, 14
      (93.3%) also performed the surgery in the year preceding this study (P = 0.001).
      The main limitation to the practice of the procedure was patients' unwillingness
      to accept surgery, as identified by 50 (89.3%) respondents. CONCLUSIONS: A low
      trabeculectomy rate of 0.9/ophthalmologist/month was found in this study. It was
      significantly associated with insufficient exposure to the surgery during
      residency training and patients' poor acceptance of the surgery.

PMID- 28513506
TI  - Surgical difficulties, success, and complication rates of orthodontic miniplate
      anchorage systems: Experience with 382 miniplates.
AB  - PURPOSE: The aim of this study was to evaluate the complications and success
      rates of the miniplates using both maxilla and mandible for orthodontic anchorage
      in growing patients. MATERIALS AND METHODS: One hundred and fifty-five
      consecutive patients (range 8.7-13.8 years) with Class II and III malocclusion
      without congenital or acquired deformities were included in this study. A total
      of 382 titanium miniplates were placed by the same surgeon. All miniplates were
      inserted under local anesthesia. Loading of the miniplates with a force of 200 g
      with the help of elastics or functional devices were initiated 3 weeks after
      surgery. RESULTS: The overall success rate of miniplate anchorage in terms of
      stability was 96.8%. Twenty-one patients reported irritation of the mucosa of the
      cheeks or lower lip after the surgery in the mandible group. Twelve miniplates
      needed to be removed and were successfully replaced. CONCLUSION: Skeletal
      anchorage miniplates is effective for correcting malocclusions. Success depends
      on proper presurgical patient counseling, minimally invasive surgery, good
      postsurgical instructions, and orthodontic follow-up.

PMID- 28513507
TI  - Early pregnancy plasminogen activator inhibitor-1 levels in Nigerian women and
      its relationship with preeclampsia.
AB  - AIM: This study compared early plasma levels of plasminogen activator inhibitor-1
      (PAI-1) in normal pregnancy and preeclampsia and determined its relationship with
      disease severity. SUBJECTS AND METHODS: This was a prospective cohort study of
      195 normotensive, aproteinuric pregnant women without prior history of
      gestational hypertension. The women were attending the Antenatal Clinic at The
      Lagos University Teaching Hospital and were within 24 weeks gestation at
      recruitment. The outcome measures were PAI-1, systolic blood pressure (SBP),
      diastolic blood pressure (DBP), and significant proteinuria. The endpoint of the
      study was the development of preeclampsia. The diagnosis of preeclampsia was made
      by the attending Obstetrician. The data were analyzed using the IBM SPSS
      statistical software. Statistical significance was set at P < 0.05. RESULTS:
      First trimester PAI-1 levels were significantly higher in the women who later
      developed preeclampsia compared to those who had a normal pregnancy (P < 0.0001).
      In these group of women who later developed preeclampsia, PAI-1 had an inverse
      relationship with gestational age (r = 0.878) whereas in normal pregnancy, PAI-1
      and gestational age had a direct relationship (r = 0.017). Second trimester
      systolic and DBP values were also significantly higher in the women who later
      developed preeclampsia compared to normal pregnancy, P = 0.007 and 0.004,
      respectively. There was, however, no correlation between PAI-1 values and SBP,
      DBP and proteinuria in the women who developed preeclampsia. CONCLUSION: Plasma
      levels of PAI-1 are increased early in pregnancies complicated by preeclampsia,
      but the lack of correlation of this marker with disease severity may limit its
      clinical utility.

PMID- 28513508
TI  - Harmful effects of formaldehyde and possible protective effect of Nigella sativa
      on the trachea of rats.
AB  - OBJECTIVE: We aimed in this study to investigate the harmful effects of
      formaldehyde (FA) inhalation and possible protective effects of Nigella sativa
      (NS) on rats' trachea. MATERIALS AND METHODS: In this study, 63 adult male rats
      were used. Animals were divided into nine groups. Group I was used as control
      group. All other groups were exposed to FA inhalation. Group III, V, VII, and IX
      were administered NS by gavage. Tissues were examined histologically, and
      immunohistochemical examination for Bax and caspase-3 immunoreactivity was
      carried out. RESULTS: Our study demonstrated that FA caused apoptosis in the
      tracheal epithelial cells. The most apoptotic activity occurred at a 10 ppm dose
      in a 13-week exposure. Distortion of tracheal epithelium and cilia loss on
      epithelial surface was present in all groups. However, NS treated Groups VII and
      IX had decreased apoptotic activity and lymphoid infiltration and protected the
      epithelial structure, despite some shedded areas. Difference of tracheal
      epithelial thickness and histological score was statistically significant between
      Group VI-VII and VIII-IX. CONCLUSION: FA induces apoptosis and tracheal
      epithelial damage in rats, and chronic administration of NS can be used to
      prevent FA-induced apoptosis and epithelial damage.

PMID- 28513509
TI  - Relationship between alexithymia and chronic periodontitis.
AB  - OBJECTIVE: The aim of this study was to investigate the potential relationship
      between alexithymia and chronic periodontitis. MATERIALS AND METHODS: A case
      control study of 222 male and female subjects aged 21-63 years was conducted. The
      participants were divided into a chronic periodontitis group (n = 114) and a
      control group (n = 108) with no history of periodontitis. The Toronto Alexithymia
      Scale (TAS-20) was used to evaluate alexithymia status of the subjects. Clinical
      data were collected on parameters such as the plaque index, bleeding on probing,
      probing depth, and the clinical attachment level (CAL). Socioeconomic data on the
      patients were also recorded. RESULTS: Chronic periodontitis group showed higher
      frequency in alexithymic patients as compared to control group. The proportion of
      high dental anxiety did not differ between the groups. The total TAS-20 score was
      statistically significantly higher in male subjects than in female subjects (P <
      0.05). The bivariate analyses of the psychometric measures and the periodontal
      parameters revealed positive correlations with the severity of periodontal
      disease/CAL and the total TAS-20 score (P < 0.05). CONCLUSION: The results of the
      current study suggest that alexithymia is a possible risk factor for chronic
      periodontitis. Further research is needed to identify the underlying mechanism.

PMID- 28513510
TI  - Factors associated with blood pressure control in predialysis chronic kidney
      disease patients: Short-term experience from a single center in Southern Nigeria.
AB  - BACKGROUND: Hypertension is a leading cause of kidney disease worldwide, and
      chronic kidney disease (CKD) is a known cause of secondary hypertension. Blood
      pressure (BP) control is a main-stay in the management of CKD because it retards
      the progression of established CKD. AIM: To determine BP control and its
      associated factors in predialysis CKD patients in a tertiary hospital setting.
      METHODOLOGY: CKD patients who attended the renal outpatient clinic during the
      period from December 2013 to June 2014 were recruited into the study. Demographic
      and clinical information were obtained from their case records. The average of
      the three most recent clinic BPs was calculated for each patient. Good BP control
      was taken as an average BP of <140/90 mmHg. RESULTS: One hundred and three
      patients (53 males and 50 females) met inclusion criteria for the study. The mean
      age of the patients was 40.6 +/- 17.4 years. Estimated glomerular filtration rate
      was <60 ml/min in 49.5% of patients. Good BP control was seen in 57 (55.3%)
      patients. Poor BP control was associated with middle age, proteinuric CKD, and
      prescription of 3 or more BP medication. CONCLUSION: BP control in predialysis
      CKD patients still needs to be optimized. Special attention should be given to
      middle-aged patients who have proteinuric CKD and those on multiple BP drugs
      without optimal BP control.

PMID- 28513511
TI  - Comparison of elasticity values of the right lobe of the liver of normal weight
      and morbidly obese Turkish patients.
AB  - INTRODUCTION: Shear wave elastography is a method for the measurement of tissue
      stiffness. The advantage of this method is that its outcome is not operator
      dependent. Our aim was to compare the elastiscity values of the right lobe of the
      liver of normal weighted and morbidly obese patients. MATERIALS AND METHODS: The
      mean elastiscity values of the right lobe of the liver were calculated for 38
      normal weighted and 37 morbidly obese patients. All the patients had no history
      of liver disease. RESULTS: The mean elastiscity value was significantly higher in
      morbidly obese patients than (25,7 +3,30 kPascal) in normal weighted patients for
      the right lobe of liver (10,55 +2,20 kPascal). CONCLUSION: Morbidly obese
      patients have a potential risk for liver fibrosis even in the absence of
      hepatosteatosis.

PMID- 28513512
TI  - Effects of laser etching on shear bond strengths of brackets bonded to fluorosed
      enamel.
AB  - AIM: To evaluate the effects of laser etching on the shear bond strengths (SBS)
      and failure modes of brackets bonded to fluorosed enamel. MATERIALS AND METHODS:
      This in vitro study included 34 fluorosed and 34 nonfluorosed teeth. Teeth were
      divided into four subgroups according to the etching procedure: Group (A) normal
      enamel etched with 37% phosphoric acid for 15 s, Group (B) nonfluorosed enamel
      etched with erbium:yttrium aluminum garnet (Er: YAG) laser for 15 s, Group (C)
      fluorosed enamel etched with 37% phosphoric acid for 30 s, Group (D) fluorosed
      enamel etched with Er: YAG laser for 30 s. After bonding of the premolar metal
      brackets, specimens were subjected to the thermal cycles. After SBS test,
      modified adhesive remnant index (ARI) by using stereomicroscope and failure modes
      with a scanning electron microscope (SEM) was determined. After bonding, one
      specimen from each group was examined under SEM to identify enamel-resin
      interfaces. ANOVA and Tukey post-hoc tests were used to compare the SBS values.
      The Kruskal-Wallis and Chi-square tests were used to analyze the distribution of
      ARI scores and failure modes of groups. RESULTS: The highest mean SBS value
      (17.56 +/- 1.05 MPa) was found in Group A, while the lowest (12.25 +/- 0.96 MPa)
      in Group D. Significant differences were found in the SBS test and failure modes
      among all groups. The differences between ARI scores of the groups were not
      significant. CONCLUSION: According to our findings, laser etching reduced the SBS
      of brackets bonded to fluorosed teeth, but provided clinically acceptable SBS
      values.

PMID- 28513513
TI  - Electrocardiographic changes and troponin T levels in children with severe
      malaria anemia and heart failure.
AB  - BACKGROUND: Severe malaria anemia is a major cause of childhood heart failure in
      malaria endemic countries. The resulting hypoxic-ischemic injuries may cause
      myocardial damage detectable by electrocardiogram (ECG) and elevated troponin T
      (cTnT) levels. OBJECTIVE: Evaluate the ECG changes and cTnT levels in children
      with severe malaria anemia compared with those who had uncomplicated malaria
      without anemia. METHODS: Consecutive children with severe malaria anemia were
      recruited as subjects while controls were age- and gender-matched children with
      uncomplicated malaria without anemia. ECG findings, cTnT levels, and the
      proportion of children with elevated cTnT were compared between subjects and
      controls. RESULTS: There were 43 subjects with a mean age of 25.7 +/- 22.9
      months. Controls were forty children; mean age was 31.2 +/- 20.0 months. All the
      subjects and 10 (25.0%) controls had ECG abnormalities. Five (11.6%) subjects and
      no control had ST segment changes, P = 0.06. Twenty-three percent of subjects
      compared to 5% of the controls had prolonged QTc, P = 0.027. Median cTnT of
      subjects (131.8 ng/L) was not significantly higher than the 85.9 ng/L of
      controls, P = 0.99. The median cTnT of subjects that died 208.9 ng/L was higher
      than in survivors 99.6 ng/L, P = 0.51. CONCLUSION: Prolonged QTc was more
      prevalent in children with severe malaria anemia compared to those without
      anemia, suggesting that children with severe malaria anemia were more prone to
      arrhythmias. The median cTnT value in the subjects was not significantly lower
      than that in controls, suggesting that children with severe malaria anemia are
      not prone to myocardial injury any more than those with uncomplicated malaria
      without anemia.

PMID- 28513514
TI  - Efficacy of polishing kits on the surface roughness and color stability of
      different composite resins.
AB  - OBJECTIVE: Different polishing kits may have different effects on the composite
      resin surfaces. The aim of this study was to evaluate the surface roughness and
      color stability of four different composites which was applied different
      polishing technique. MATERIALS AND METHODS: Thirty specimens were made for each
      composite resin group (nanohybrid, GrandioSo-GS; nanohybrid, Clearfil Majesty
      Esthetic-CME; hybrid, Valux Plus-VP; micro-hybrid, Ruby Comp-RC; [15 mm in
      diameter and 2 mm height]), with the different monomer composition and particle
      size from a total of 120 specimens. Each composite group was divided into three
      subgroups (n = 10). The first subgroup of the each composite subgroups served as
      control (C) and had no surface treatment. The second subgroup of the each
      composite resin groups was polished with finishing discs (Bisco Finishing Discs;
      Bisco Inc., Schaumburg, IL, USA). The third subgroup of the each composite resin
      was polished with polishing wheel (Enhance and PoGo, Dentsply, Konstanz,
      Germany). The surface roughness and the color differences measurement of the
      specimens were made and recorded. The data were compared using Kruskal-Wallis
      test, and regression analysis was used in order to examine the correlation
      between surface roughness and color differences of the specimens (alpha = 0.05).
      RESULTS: The Kruskal-Wallis test indicated significant difference among the
      composite resins in terms of DeltaE (P < 0.05), and there was no statistically
      significant difference among composite resins in terms of surface roughness (P >
      0.05). Result of the regression analysis indicated statistically significant
      correlation between Ra and DeltaE values (P < 0.05, r2 = 0.74). CONCLUSION: The
      findings of the present study have clinical relevance in the choice of polishing
      kits used.

PMID- 28513515
TI  - Relationship between knowledge and quality of asthma care among physicians in
      South-West Nigeria.
AB  - INTRODUCTION: Adequate knowledge of asthma management and adherence to
      international guidelines are known to increase the quality of care offered by
      Physicians. We conducted this study to assess the level of asthma knowledge and
      quality of care among physicians practicing in Ondo State. METHODS: We conducted
      a cross sectional survey of 96 physicians from various specialties participating
      in a continuous professional development (CPD) lecture using adapted
      questionnaires. RESULT: Respondents ranged in age from 23-62years (42.5+/-19.4).
      There were more male (70%). The minority (17%) had additional postgraduate
      medical qualifications. There was a high distribution of correct answers for
      individual knowledge questions. The greatest areas of knowledge gaps appeared in
      diagnostic instruments, asthma severity and drugs. We observed gaps regarding the
      use of GINA guidelines (6%) and prescribing combined inhaled steroid and long
      acting bronchodilator for patients who are not controlled on inhaled steroid
      alone (29%). A large number of the respondents do not confirm the diagnosis of
      asthma by spirometry (32%). Only 8% of the respondents with high knowledge
      reported a corresponding high quality of Asthma care. CONCLUSION: We concluded
      that although physicians in South-West Nigeria appear to have good knowledge,
      there are areas of gap in the quality of asthma care with regards to standard
      guideline. There is need for constant training and re-training of physicians in
      order to keep them up to date with international guidelines. In addition,
      increase access to diagnostic facilities and adapting international guideline to
      local realities will help improve standard of Asthma care.

PMID- 28513516
TI  - Admission hyperglycemia an independent predictor of outcome in acute ischemic
      stroke: A longitudinal study from a tertiary care hospital in South India.
AB  - BACKGROUND: Stroke is one of the important causes of long-term disability-related
      deaths worldwide. Incidence and prevalence of stroke have been steadily
      increasing in India. Increasing interest has been focused on the role of
      admission hyperglycemia in the evolution of acute ischemic stroke. Very few
      studies were conducted in south India; hence, we intended to do this study.
      METHODS: A total of 198 patients with acute ischemic stroke were included in a
      hospital-based longitudinal study to identify the independent factors
      (demographic, clinical, and biochemical parameters) associated with poor outcome
      (functional impairment-mRS >= 3 and mortality at 90 days of follow-up. RESULTS:
      Nearly, 75% of the patients presented with moderate-to-severe stroke. Out of the
      198 patients, 117 (59%) had severe disability at admission. At 90 days of follow
      up, it was observed that only 10 (5.5%) had severe disability. Patients with
      hyperglycemia exhibited greater functional impairment, that is, 96 out of 111
      study subjects had modified Rankin score (mRS) >=3, than those with normoglycemia
      (P < 0.0001). Mortality was high in hyperglycemics when compared with
      normoglycemics, that is, out of the 20 deaths, 13 patients had hyperglycemia and
      seven had normoglycemia at presentation (P < 0.015). Logistic regression analysis
      predicted that higher capillary blood glucose at first presentation, moderate-to
      severe stroke, poor drug compliance, stress hyperglycemia, and newly detected
      diabetes mellitus were associated with poor functional outcome at 90 days of
      follow-up. CONCLUSION: Stress hyperglycemia in stroke was associated with higher
      risk of poor functional outcome in acute ischemic stroke. Hyperglycemia at stroke
      onset without prior history of diabetes mellitus have particularly poor
      prognosis, than those with hyperglycemia in known diabetes.

PMID- 28513517
TI  - Comparison of arch width changes following orthodontic treatment with and without
      extraction using three-dimensional models.
AB  - OBJECTIVE: To compare the arch width changes in patients treated fixed
      orthodontic mechanics without extraction (Group 1), with upper and lower first
      premolar extractions (Group 2), and with upper first premolar extraction only
      (Group 3). MATERIALS AND METHODS: The study was conducted with pre- and post
      treatment digital models from 240 patients. Anterior, middle, and posterior
      distances were measured on pre- and post-treatment models. At T1 measurements,
      the distance among the canine cusp tips, the second premolar buccal cusp tips,
      and the first molar mesiobuccal cusp tips were measured. In addition, the
      distance (D) between the intercanine and intermolar lines and the distance (D')
      between the interpremolar and intermolar lines were defined on the anatomic y
      axis, and this distance was maintained in calculating posttreatment measurements
      (T2). Mandibular and maxillary arch width changes were evaluated within and
      between groups. RESULTS: Anterior, middle, and posterior arch widths increased
      significantly in Groups 1 and 3. Maxillary anterior and middle arch widths also
      increased in Group 2, but the increases were not statistically significant.
      Changes in maxillary anterior and middle arch widths were higher in Groups 1 and
      3 when compared to Group 2. However, there was no statistically significant
      difference in mandibular arch changes between the groups. CONCLUSION: Extraction
      treatment mechanics did not cause narrow dental arches, but nonextraction
      treatment increased arch width in all 3 measurements. Treatments with only upper
      arch extraction showed similar results with nonextraction treatment.

PMID- 28513518
TI  - Firearm injuries received in emergency room of a Nigerian Teaching Hospital:
      Aanalysis of pattern, morbidity, and mortality.
AB  - BACKGROUND: The morbidity and mortality associated with civilian firearm injury
      in developing countries is appreciable. The increasing incidence of gunshot
      casualties received in hospital emergency rooms is an emerging concern. The aim
      of this study was to determine the pattern and outcome of firearm injuries in a
      civilian setting of a developing country. MATERIALS AND METHOD: This was a
      retrospective analysis of data on the entire patients with firearm injury
      received in the emergency room of Federal Teaching Hospital Abakaliki from
      January 2005 to December 2014. RESULTS: There were 214 casualties, male-to-female
      ratio was 8:1, and mean age was 31.7 +/- 0.80 years. The causes of injuries were
      armed robbery (59.9%), assault (33.6%), and accidental (6.5%). The incidence of
      armed robbery-related injury peaked in May and was higher in rainy season (P <
      0.018), urban areas (P < 0.001) and at night-time (P < 0.033), whereas the
      incidence of assault-related injury peaked in April and was higher in dry season
      in rural areas and at day-time. Duration of hospital admission ranged from 1 to
      184 days and mean was 16 days. Prolonged duration of hospital admission
      correlated with perforating wound (P < 0.001), high-velocity gunshot (P < 0.001),
      fractures (P < 0.001) and wound infection (P < 0.001). Preventable death rate was
      high, although mortality rate was 5.6%. A high mortality rate correlated with
      visceral injury (P < 0.001) and hypovolaemic shock (P < 0.001). CONCLUSION: The
      temporal distribution of firearm injury varies in location and aetiology of
      gunshot. This and the factors for relatively high morbidity and preventable death
      rate observed call for preventive strategies as well as improvement in pre
      hospital and emergency room care.

PMID- 28513519
TI  - Attitude and knowledge of family medicine practitioners towards the association
      between periodontal disease and obesity.
AB  - OBJECTIVES: To assess the attitude and knowledge of family medicine practitioners
      (FMPs) towards the association between periodontal disease and obesity. MATERIALS
      AND METHODS: A cross-sectional study was performed and a 13-item survey
      questionnaire was given to FMPs practicing in 12 different teaching hospitals in
      Karachi, Pakistan. The questions were aimed at exploring the knowledge of FMP's
      regarding the association of obesity and periodontal disease and their attitude
      towards the association of obesity and periodontal disease. Chi-square and
      Spearman co-efficient were conducted to compare subgroups and correlate factors
      with the knowledge score of FMPs. RESULTS: A total of 314 questionnaires were
      completed (response rate = 92%). Median age of participants was 41 years and 57%
      were females. Almost 61% of FMPs answered all the knowledge questions correctly
      and 64% reported moderate understanding of the association between periodontal
      health and obesity. Nearly 73% FMPs inquired from obese patients regarding the
      periodontal disease and more than half (58%) refer patients to a dentist for
      evaluation. More than half of FMPs perform periodontal disease screening. Nearly
      all FMPs considered informing obese patients regarding periodontal disease as one
      of their roles. CONCLUSIONS: FMP's play an important role in the early diagnosis,
      prevention and treatment of periodontal conditions in obese patients. More than
      two thirds of FMPs showed good knowledge of the association of obesity and
      periodontal disease. The attitudes of FMPs towards assessing and referring obese
      patients at a risk of having periodontal disease were reassuring.

PMID- 28513520
TI  - Clinical assessment of mineral trioxide aggregate in the treatment of deep
      carious lesions.
AB  - OBJECTIVE: This clinical study aimed to assess the effectiveness of mineral
      trioxide aggregate (MTA) and calcium hydroxide (Ca[OH]2) in the treatment of deep
      carious lesions using the direct complete caries excavation technique. SUBJECTS
      AND METHODS: Hundred permanent molars/premolars were capped either with Ca (OH)2
      (n = 49) or MTA (n = 51) and restored with composite resin in 73 patients.
      Periapical radiographs were taken prior to the treatment, at 6 months and 12
      months. Two calibrated examiners clinically and radiographically assessed the
      periapical pathology and pulpal symptoms. Inter-group comparisons of the observed
      values were analyzed using Fisher's exact test. Significance was predetermined at
      alpha = 0.05. RESULTS: Recall rates were 100% at 6 and 12 months. Four teeth
      capped with Ca(OH)2 (two each at the end of 6 and 12 months) and one tooth capped
      with MTA (at the end of 12 months) received endodontic emergency treatment
      because of symptoms of irreversible pulpitis that were clinically and/or
      radiographically established. There was no significant difference between the
      protection of the tooth vitality and pulp capping agents at 6 and 12 months (P =
      0.238, P = 0.606, respectively). CONCLUSION: Both materials were clinically
      applicable at the end of 12 months.

PMID- 28513521
TI  - Otorhinolaryngological emergencies in a Tertiary Hospital in Port Harcourt.
AB  - BACKGROUND: Emergencies are not uncommon in a typical otorhinolaryngological
      (ORL) clinic. The knowledge of the profile and prevalence of these emergencies
      will go a long way in helping to equip as well as aid proper and prompt
      management of these conditions so as to reduce their morbidity and mortality.
      PATIENTS AND METHODS: A descriptive retrospective 8 years review of all patients
      that presented to the ENT Surgery Department from January 2004 to December 2012.
      This includes referrals from the accident and emergency as well as the children
      emergency ward. The patients case files, the ward, and theatre records were the
      source of data. Data collected included; age, sex, presentations, diagnosis, and
      management. RESULTS: There were a total number of 5660 patients that presented as
      emergencies, however only 2160 cases were real emergencies. Males were 1328 and
      females 832 with a ratio of 1.6:1. The age ranged from 6 months to 70 years. The
      age range 0-10 years were the most affected 670 (31.02%) followed by age range 21
      30 years 534 (24.72%). The least was 61-70 years 26 (1.20%). Foreign body
      aspiration/ingestion/insertion was the commonest emergency 900 cases (41.7%)
      followed by trauma 650 (30.09%). There were five cases (0.23%) of mortality
      recorded. Respiratory distresses from upper airway obstruction, dysphagia, and
      odynophagia were the common presentations. Direct laryngoscopy, esophagoscopy,
      and tracheostomy were the commonest form of management. CONCLUSION: ORL
      emergencies are common. The pediatric age group is the most affected; foreign
      body and trauma comprise the commonest emergency in our environment.

PMID- 28513522
TI  - Comparison between olfactory function of pregnant women and non-pregnant women in
      reproductive age group in Ibadan, Nigeria.
AB  - BACKGROUND: Pregnant women require normal olfactory function in order to develop
      good appetite for healthy living and normal fetal development. This study was
      carried out to investigate and compare olfactory function of pregnant women with
      non-pregnant women. METHODS: This was a case control study of women in
      reproductive age group at the University College Hospital, Ibadan, Nigeria from
      July 2014 to February 2015. Consecutive 70 pregnant women and 70 non-pregnant
      women (controls) without rhinologic symptoms were studied. A structured
      questionnaire was administered to obtain participants' information on socio
      demographics, pregnancy history, and ability to perceive smell. They subjectively
      rated their olfactory function on a visual analogue scale of 0 - 100. Olfactory
      threshold (OT), discrimination (OD), identification (OI) scores and TDI of both
      groups were determined with"Sniffin' sticks"kits and compared. The level of
      significance was P<0.05. RESULTS: The mean age of the pregnant women was 30.5+/
      3.9years and control was 28.5+/-6.6years. There were more pregnant women (7.1%)
      with hyposmia than the non-pregnant women (2.9%). The subjective rating of
      olfactory function was 68.2+/-24.9 (median 70) and 72.3+/-21.6 (median 69) in
      pregnant women and controls respectively. The mean OT, OD, OI, TDI scores were
      higher in pregnant women than the controls. However, it was only in OI (P=0.000)
      and TDI (P=0.012) that the differences were significant. CONCLUSIONS: Pregnant
      women have olfactory dysfunction more than the non-pregnant women of reproductive
      age group. Also, they have tendency to develop loss of cognitive olfactory
      information more than the non-pregnant women.

PMID- 28513523
TI  - The efficacy of sequential therapy in eradication of Helicobacter pylori in
      Turkey.
AB  - BACKGROUND AND AIM: Most of the studies about sequential therapy that have been
      reported from Turkey were levofloxacin based. We aimed to compare the
      Helicobacter pylori (H. pylori) eradication rates of standard triple, sequential
      and quadruple therapies including claritromycin regimes in this study. MATERIALS
      AND METHODS: A total of 160 patients with dyspeptic symptoms were enrolled to the
      study. The patients were randomized to four groups of treatment protocols. And 40
      patients received standard triple therapy for 2 weeks, 40 patients received
      bismuth containing quadruple therapy for 2 weeks, 40 patients received 5 + 5
      clarithromycin-based sequential therapy, and 40 patients received 7 + 7
      clarithromycin-based sequential therapy. H. pylori eradication was assessed by C
      14 urea breath test 4 weeks after therapy. RESULTS: Out of 160 patients with H.
      pylori infection, 131 (81.9%) were eradicated successfully and 29 (18.1%) failed
      to eradicate H. pylori infection. H. pylori eradication was achieved in 28 of 40
      patients receiving standard triple therapy (70%), in 33 of 40 patients receiving
      quadruple therapy (82.5%), in 37 of 40 patients receiving 5 + 5 sequential
      therapy (92.5%), and in 33 of 40 patients receiving 7 + 7 sequential therapy (82.
      5%). Statistics revealed that 5 + 5 sequential therapy led to significantly
      higher H. pylori eradication rates compared with that of standard triple therapy
      (P = 0.019). There was no statically difference between 5 + 5 sequential therapy
      and the other therapy groups' eradication rates, but it was higher than all of
      the protocols. H. pylori eradication rate with sequential therapy in our patients
      with nonulcer dyspepsia was higher than those of patients with standard therapy
      (93% versus 82%, respectively, P>0.05). CONCLUSION: 5 + 5 sequential therapy was
      associated with significantly higher eradication rate of H. pylori compared with
      standard triple therapy in our study cohort.

PMID- 28513524
TI  - Ureterolithiasis: Management in an environment with limited facilities.
AB  - BACKGROUND: In the past 2-3 decades, there has been a dramatic development in the
      techniques of stone removal. This study highlights the management of symptomatic
      ureteral stones in an environment without such facilities. MATERIALS AND METHODS:
      Sixty-nine patients, comprising 53 (76.8%) males and 16 (23.2%) females,
      diagnosed of symptomatic ureteric calculi within the study period in two tertiary
      health institutions were included in the study. Thorough history taking and
      physical examinations were performed. Extensive laboratory investigations using
      blood and urine specimens were carried out. Imaging studies, ultrasonography,
      intravenous urography, and computerized tomographic scan were used to locate the
      position and size of the calculi. RESULTS: Forty-six (66.7%) patients presented
      with excruciating flank ureteric colic radiating to the groin in 16 (23.2%)
      patients and hematuria in 62 (89.9%) patients. Bilateral ureteric calculi
      occurred in 3 (4.3%) patients. Eleven (15%) stones passed spontaneously. 33
      (47.8%) patients had uneventful open surgery. The stones were mixed in nature.
      CONCLUSION: Management of ureteric stones in our environment is affected by delay
      in presentation, low level of awareness of urinary stone disease, lack of modern
      endourological equipment, and paucity of urological surgeons. Finally, medical
      treatment should be explored for stones below 10 mm in size.

PMID- 28513525
TI  - Rehabilitation effect of exercise with soft tissue manipulation in patients with
      lumbar muscle strain.
AB  - OBJECTIVE: To study the rehabilitation effect of exercise with soft tissue
      manipulation therapy for patients with lumbar muscle strain. METHODS: Patients
      with lumbar muscle strain who met the inclusion criteria for study were randomly
      divided into control and experimental groups. Conventional therapy (i.e., triple
      therapy of needle, moxibustion, and cupping jar) was implemented for control
      group patients with lumbar muscle strain, whereas the combination therapy of
      exercise with manipulation was implemented for experimental group patients with
      lumbar muscle strain. Pain levels of the two groups of patients were graded using
      the VAS score, and finally, the rehabilitation effect of the two groups of
      patients was evaluated. Comparative analysis was performed using SPSS17.0
      software, t-test, variance and chi2 test, and other statistical methods. RESULTS:
      After treatment, there is a significant difference in average visual analogue
      scale (VAS) score between experimental group and control group, which meets P <
      0.05; difference in joint range of motion between experimental group patients and
      control group patients was P < 0.05; the total treatment efficiency of
      experimental group patients was 99%, whereas that of control group was 79%.
      CONCLUSION: Rehabilitation effect of exercise with soft tissue manipulation
      therapy for lumbar muscle strain is more significant.

PMID- 28513526
TI  - Cecal carcinoid tumor in a nigerian man: A case report and review of literature.
AB  - Carcinoid tumors are rare neuroendocrine tumors that have been reported in a wide
      range of organs but most commonly involve the gastrointestinal tract (stomach,
      ileum, appendix, and colon), and rarely ovary and thymus. We present a case of a
      56-year-old Nigerian man with a cecal carcinoid tumor that was surgically
      removed. A 56-year-old Nigerian man, presented to our hospital with a year
      history of right-sided lower abdominal fullness, audible bowel sounds, occasional
      diarrhea, nausea, vomiting, and epigastric pain. There was no history of
      hematochezia or passage of melena stool. Colonoscopy revealed a cecal mass
      occupying more than two-thirds of the cecal lumen. Histology confirmed carcinoid
      tumor (well-differentiated neuroendocrine tumor), which was surgically removed.
      Carcinoid tumors are slow growing rare neuroendocrine tumors. Mortality is low if
      it is diagnosed early.

PMID- 28513527
TI  - Management of pediatric mandibular fracture using orthodontic vacuum-formed
      thermoplastic splint: A case report and review of literature.
AB  - Fractures of the mandible are relatively less frequent in children when compared
      to adults. The anatomic features of children are protected. Children have a
      higher adaptation to maxillofacial fractures compared to adults. Treatment
      principles of mandibular fractures in children differ from that of adults due to
      concerns regarding mandibular growth and the developing dentition. A case of a 6
      year-old boy with fractured mandibular symphysis managed by closed reduction
      using a vacuum formed thermoplastic splint and circummandibular wiring is
      presented. This article also provides a review of the literature regarding the
      management of mandibular fracture in young children.

PMID- 28513528
TI  - Complete upper urinary tract obstruction caused by penetrating pellet injury of
      the ureterintroduction.
AB  - Ureteral injuries due to gunshots are tend to be misdiagnosed because of
      concomitant vascular and intraabdominal organ wounds. Our case is a 23-year-old
      man who was admitted to the hospital with multiple abdominal gunshot wounds.
      Laboratory findings showed worsening anemia, and the computed tomography (CT)
      scan showed multiple lead bullets inside the abdomen and retroperitoneum. Patient
      was then taken to the operation room for laparatomy. There were many intestinal
      injuries and also a stable retroperitoneal hematoma. There was no ureteral injury
      mentioned in the operation note or the initial CT report. Two weeks after this
      operation, the patient developed significant urine leakage from the abdominal
      wounds. Ureteral J stent placement was our first choice of treatment. This was
      complicated with a late ureteral obstruction. The final treatment was an
      ureteroureterostomy. Diagnosing ureteral injuries due to traumatic causes can be
      hard in most of the cases. Physicians should consider early evaluation of the
      patient for ureteral leakage if there is suspicion about ureteral injury.

PMID- 28513529
TI  - Total gastric necrosis: A case report and literature review.
AB  - Total gastric necrosis is a rare disease and easy to misdiagnose. Here we report
      a rare case of total gastric necrosis. The patient, an 89-year-old male, had
      epigastric pain for 5 days. He was transferred to our hospital because of
      intraperitoneal hemorrhage and hypovolemic shock. We performed an emergency
      laparotomy. During the surgery, we found a total of 3500ml unclotted blood in the
      abdomen, splenic infarction and gastric necrosis. Total gastrectomy with Roux-en
      Y esophagojejunostromy and splenectomy was performed. However, the patient died
      on the second day after the surgery. This case suggests that surgical treatment
      should be performed as early as possible when ischemia of abdominal organs is
      suspected.

PMID- 28513530
TI  - An analysis of child deaths by suicide in Queensland Australia, 2004-2012. What
      are we missing from a preventative health services perspective?
AB  - BACKGROUND: This article analyzes case descriptions of child suicides from 2004
      to 2012 to inform future policy and practice. METHODS: Quantitative data and case
      descriptions for 159 child suicides (less than 18 years) in Queensland,
      Australia, were analyzed quantitatively using SPSS and qualitatively using
      automated content analysis (Leximancer). RESULTS: More than three quarters of
      child suicides involved hanging and 81% of suicides occurred in the family home.
      Less than 20% of the deceased left a note, however there was evidence of planning
      in 54% of cases. Most common triggering events were family conflicts.
      CONCLUSIONS: Effective suicide prevention interventions require a comprehensive
      understanding of risk factors. Quality of case descriptions varied widely, which
      can hamper injury prevention efforts through an incomplete understanding of
      characteristics of and important factors in child suicide. Additional attention
      and resources dedicated to this public health issue could enhance the development
      and implementation of effective intervention strategies targeting child and
      adolescent suicide.

PMID- 28513531
TI  - Who should lead a trauma team: Surgeon or non-surgeon? A systematic review and
      meta-analysis.
AB  - BACKGROUND: Presence of a trauma team leader (TTL) in the trauma team is
      associated with positive patient outcomes in major trauma. The TTL is
      traditionally a surgeon who coordinates the resuscitation and ensures adherence
      to Advanced Trauma Life Support (ATLS) guidelines. The necessity of routine
      surgical leadership in the resuscitative component of trauma care has been
      questioned by some authors. Therefore, it remains controversial who should lead
      the trauma team. We aimed to evaluate outcomes associated with surgeon versus non
      surgeon TTLs in management of trauma patients. METHODS: In accordance with
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      statement standards, we performed a systematic review. Electronic databases
      MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials
      (CENTRAL) were searched to identify randomized and non-randomized studies
      investigating outcomes associated with surgeon versus non-surgeon TTL in
      management of trauma patients. The Newcastle-Ottawa scale was used to assess the
      methodological quality and risk of bias of the selected studies. Fixed-effect
      model was applied to calculate pooled outcome data. RESULTS: Three retrospective
      cohort studies, enrolling 2,519 adult major trauma patients were included. Our
      analysis showed that there was no difference in survival [odds ratio (OR): 0.82,
      95% confidence interval (CI) 0.61-1.10, P=0.19] and length of stay when trauma
      team was led by surgeon or non-surgeon TTLs; however, fewer injuries were missed
      when the trauma team was led by a surgeon (OR: 0.48, 95% CI 0.25-0.92, P=0.03).
      CONCLUSIONS: Despite constant debate, the comparative evidence about outcomes
      associated with surgeon and non-surgeon trauma team leader is insufficient. The
      best available evidence suggests that there is no significant difference in
      outcomes of surgeon or non-surgeon trauma team leaders. High quality randomized
      controlled trials are required to compare the effectiveness of surgeon and non
      surgeon trauma team leaders in order to resolve the controversy about who should
      lead the trauma team. Clinically significant missed injuries should be considered
      as important outcome in future studies.

PMID- 28513532
TI  - Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites
      with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients.
AB  - Peritoneal ascites are a distinguishable feature of patients with advanced
      epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has
      been reported in EOC-associated ascites, which also can or not contain malignant
      cells. The goal of this study was to analyze the functional characteristics of
      natural killer (NK) cells from EOC-associated ascites in terms of their
      expression of activating receptors and ascites' contents of lymphocyte subtypes,
      cytokine profile and presence of EOC cells. NK cell function was evaluated by the
      expression of the degranulation marker CD107a in resting and interleukin (IL)-2
      stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC
      cell-free ascites was significantly (p < 0.05) higher than all the other groups,
      either in their resting state or after IL-2 stimulation, suggesting a previous
      local stimulation. In contrast, treatment with IL-2 had no effect on NK cells
      from ascites with EOC cells. The amount of regulatory T cells was significantly
      higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with
      EOC cells also had higher levels of tumor necrosis factor (TNF)-alpha, suggesting
      inflammation related to the malignancy. In conclusion, the functional performance
      of NK cells was distinct between EOC cell-free ascites and ascites with EOC
      cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was
      consistent with an immunosuppressive tumor microenvironment.

PMID- 28513533
TI  - Deleterious Metabolic Effects of High Fructose Intake: The Preventive Effect of
      Lactobacillus kefiri Administration.
AB  - Modern lifestyle and diets have been associated with metabolic disorders and an
      imbalance in the normal gut microbiota. Probiotics are widely known for their
      health beneficial properties targeting the gut microbial ecosystem. The aim of
      our study was to evaluate the preventive effect of Lactobacillus kefiri (L.
      kefiri) administration in a fructose-rich diet (FRD) mice model. Mice were
      provided with tap water or fructose-added (20% w/v) drinking water supplemented
      or not with L. kefiri. Results showed that probiotic administration prevented
      weight gain and epidydimal adipose tissue (EAT) expansion, with partial reversion
      of the adipocyte hypertrophy developed by FRD. Moreover, the probiotic prevented
      the increase of plasma triglycerides and leptin, together with the liver
      triglyceride content. Leptin adipocyte secretion was also improved by L. kefiri,
      being able to respond to an insulin stimulus. Glucose intolerance was partially
      prevented by L. kefiri treatment (GTT) and local inflammation (TNFalpha; IL1beta;
      IL6 and INFgamma) was completely inhibited in EAT. L. kefiri supplementation
      generated an impact on gut microbiota composition, changing Bacteroidetes and
      Firmicutes profiles. Overall, our results indicate that the administration of
      probiotics prevents the deleterious effects of FRD intake and should therefore be
      promoted to improve metabolic disorders.

PMID- 28513536
TI  - Resonance Rayleigh Scattering and SERS Spectral Detection of Trace Hg(II) Based
      on the Gold Nanocatalysis.
AB  - Mercury (Hg) is a heavy metal pollutant, there is an urgent need to develop
      simple and sensitive methods for Hg(II) in water. In this article, a simple and
      sensitive resonance Rayleigh scattering (RRS) method was developed for
      determination of 0.008-1.33 umol/L Hg, with a detection limit of 0.003 MUmol/L,
      based on the Hg(II) regulation of gold nanoenzyme catalysis on the HAuCl4-H2O2 to
      form gold nanoparticles (AuNPs) with an RRS peak at 370 nm. Upon addition of
      molecular probes of Victoria blue B (VBB), the surface-enhanced Raman scattering
      (SERS) peak linearly decreased at 1612 cm-1 with the Hg(II) concentration
      increasing in the range of 0.013-0.5 MUmol/L. With its good selectivity and good
      accuracy, the RRS method is expected to be a promising candidate for determining
      mercury ions in water samples.

PMID- 28513535
TI  - Characterization of Chinese Unifloral Honeys Based on Proline and Phenolic
      Content as Markers of Botanical Origin, Using Multivariate Analysis.
AB  - The phenolic and proline content were determined in honey samples of different
      floral origins (rapeseed, sunflower, buckwheat and Codonopsis) from five
      different regions of China. The phenolic and proline profile of these samples
      were used to construct a statistical model to distinguish honeys from different
      floral origins. Significant differences were identified among the studied honey
      samples from multivariate chemometric methods. The proline content varied among
      the four types of honeys, with the values decreasing in the order: buckwheat >
      Codonopsis > sunflower > rapeseed. Rapeseed honeys contained a high level of
      benzoic acid, while rutin, p-coumaric acid, p-hydroxybenzoic acid were present at
      relatively high levels in buckwheat honeys. Principal component analysis (PCA)
      revealed that rapeseed honey could be distinguished from the other three
      unifloral honeys, and benzoic acid, proline and kaempferol could serve as
      potential floral markers. Using 18 phenolic compounds and proline the honey
      samples were satisfactorily classified according to floral origin at 94% correct
      prediction by linear discriminant analysis (LDA). The results indicated that
      phenolic compounds and proline were useful for the identification of the floral
      origin of the four type honeys.

PMID- 28513537
TI  - Computational Predictions for Single Chain Chalcogenide-Based One-Dimensional
      Materials.
AB  - Exfoliation of multilayered materials has led to an abundance of new two
      dimensional (2D) materials and to their fabrication by other means. These
      materials have shown exceptional promise for many applications. In a similar
      fashion, we can envision starting with crystalline polymeric (multichain)
      materials and exfoliate single-chain, one-dimensional (1D) materials that may
      also prove useful. We use electronic structure methods to elucidate the
      properties of such 1D materials: individual chains of chalcogens, of silicon
      dichalcogenides and of sulfur nitrides. The results indicate reasonable
      exfoliation energies in the case of polymeric three-dimensional (3D) materials.
      Quantum confinement effects lead to large band gaps and large exciton binding
      energies. The effects of strain are quantified and heterojunction band offsets
      are determined. Possible applications would entail 1D materials on 3D or 2D
      substrates.

PMID- 28513534
TI  - Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic
      Acids.
AB  - Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative
      disorders that affect humans and other mammals. The etiologic agents common to
      these diseases are misfolded conformations of the prion protein (PrP). The
      molecular mechanisms that trigger the structural conversion of the normal
      cellular PrP (PrPC) into the pathogenic conformer (PrPSc) are still poorly
      understood. It is proposed that a molecular cofactor would act as a catalyst,
      lowering the activation energy of the conversion process, therefore favoring the
      transition of PrPC to PrPSc. Several in vitro studies have described physical
      interactions between PrP and different classes of molecules, which might play a
      role in either PrP physiology or pathology. Among these molecules, nucleic acids
      (NAs) are highlighted as potential PrP molecular partners. In this context, the
      SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has
      proven extremely valuable to investigate PrP-NA interactions, due to its ability
      to select small nucleic acids, also termed aptamers, that bind PrP with high
      affinity and specificity. Aptamers are single-stranded DNA or RNA
      oligonucleotides that can be folded into a wide range of structures (from harpins
      to G-quadruplexes). They are selected from a nucleic acid pool containing a large
      number (1014-1016) of random sequences of the same size (~20-100 bases). Aptamers
      stand out because of their potential ability to bind with different affinities to
      distinct conformations of the same protein target. Therefore, the identification
      of high-affinity and selective PrP ligands may aid the development of new
      therapies and diagnostic tools for TSEs. This review will focus on the selection
      of aptamers targeted against either full-length or truncated forms of PrP,
      discussing the implications that result from interactions of PrP with NAs, and
      their potential advances in the studies of prions. We will also provide a
      critical evaluation, assuming the advantages and drawbacks of the SELEX
      (Systematic Evolution of Ligands by Exponential Enrichment) technique in the
      general field of amyloidogenic proteins.

PMID- 28513538
TI  - Room-Temperature Ammonia Sensor Based on ZnO Nanorods Deposited on ST-Cut Quartz
      Surface Acoustic Wave Devices.
AB  - Using a seed layer-free hydrothermal method, ZnO nanorods (NRs) were deposited on
      ST-cut quartz surface acoustic wave (SAW) devices for ammonia sensing at room
      temperature. For a comparison, a ZnO film layer with a thickness of 30 nm was
      also coated onto an ST-cut quartz SAW device using a sol-gel and spin-coating
      technique. The ammonia sensing results showed that the sensitivity, repeatability
      and stability of the ZnO NR-coated SAW device were superior to those of the ZnO
      film-coated SAW device due to the large surface-to-volume ratio of the ZnO NRs.

PMID- 28513540
TI  - Enterotoxigenic Escherichia coli Flagellin Inhibits TNF-Induced NF-kappaB
      Activation in Intestinal Epithelial Cells.
AB  - Enterotoxigenic Escherichia coli (ETEC) causes childhood diarrhea in developing
      countries. ETEC strains produce the heat-labile enterotoxin (LT) and/or heat
      stable enterotoxins (ST) and encode a diverse set of colonization factors used
      for adherence to intestinal epithelial cells. We previously found that ETEC
      secretes a heat-stable protein we designated as ETEC Secreted Factor (ESF) that
      inhibits the extent of NF-kappaB activation normally induced by tumor necrosis
      factor alpha (TNF). Here we fractionated ETEC supernatants using fast protein
      liquid chromatography (FPLC) and determined that ETEC flagellin was necessary and
      sufficient to protect IkappaBalpha from degradation in response to TNF
      stimulation. These data suggest a potentially novel mechanism by which ETEC may
      evade the host innate immune response by down-regulating NF-kappaB-dependent host
      responses.

PMID- 28513541
TI  - Promoting Healthy Lifestyle and Well-Being in Adolescents through Outdoor
      Physical Activity.
AB  - Health-enhancing physical activities (PA) performed outdoors could markedly
      contribute to the adoption of a healthy lifestyle in adolescence. The differences
      between PA preferences and actual opportunities for these PA are an issue that
      has received frequent attention. To date, the extent to which these differences
      are reflected in adolescents meeting PA recommendations and their well-being has
      not been explored. In total, 10,086 respondents took part in an on-line research
      project regarding PA preferences. Of them, 2446 also completed the International
      Physical Activity Questionnaire (Long Form) and the World Health Organization
      (WHO) W-5 questionnaire to assess well-being. Finally, 1278 of these respondents
      were involved in objective PA monitoring using pedometers. The study aimed to
      explore the prevalence and trends regarding outdoor PA. Moreover, we assessed
      whether the agreement between preferred PA and PA actually undertaken was
      associated with higher odds for meeting PA recommendations and achieving a higher
      level of well-being. Of a selection of outdoor activities, Czech and Polish boys
      preferred cycling, swimming, and downhill skiing, while girls preferred swimming
      activities, skating, and cycling. The agreement between preferred and PA actually
      undertaken was associated with higher odds for meeting the weekly PA
      recommendations and higher levels of well-being both in boys and girls.
      Evaluation of outdoor PA preferences and taking these preferred activities into
      account when forming conditions for them was important in the efficient promotion
      of the physical and mental health of adolescents.

PMID- 28513542
TI  - Biomimetic Synthesis of Resveratrol Trimers Catalyzed by Horseradish Peroxidase.
AB  - Biotransformation of trans-resveratrol and synthetic (+/-)-epsilon-viniferin in
      aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants
      resulted in the isolation of two new resveratrol trimers (3 and 4), one new
      resveratrol derivative (5) with a dihydrobenzofuran skeleton, together with two
      known stilbene trimers (6 and 7), and six known stilbene dimers (8-13). Their
      structures and relative configurations were identified through spectral analysis
      and possible formation mechanisms were also discussed. Among these oligomers,
      trimers 6 and 7 were obtained for the first time through direct transformation
      from resveratrol. Results indicated that this reaction is suitable for the
      preparation of resveratrol oligomers with a complex structure.

PMID- 28513539
TI  - The Interplay between Oncogenic Signaling Networks and Mitochondrial Dynamics.
AB  - Mitochondria are dynamic organelles that alter their organization in response to
      a variety of cellular cues. Mitochondria are central in many biologic processes,
      such as cellular bioenergetics and apoptosis, and mitochondrial network
      morphology can contribute to those physiologic processes. Some of the biologic
      processes that are in part governed by mitochondria are also commonly deregulated
      in cancers. Furthermore, patient tumor samples from a variety of cancers have
      revealed that mitochondrial dynamics machinery may be deregulated in tumors. In
      this review, we will discuss how commonly mutated oncogenes and their downstream
      effector pathways regulate the mitochondrial dynamics machinery to promote
      changes in mitochondrial morphology as well as the physiologic consequences of
      altered mitochondrial morphology for tumorigenic growth.

PMID- 28513543
TI  - Chronic Exposure to Uranium from Gestation: Effects on Behavior and Neurogenesis
      in Adulthood.
AB  - Uranium exposure leads to cerebral dysfunction involving for instance
      biochemical, neurochemical and neurobehavioral effects. Most studies have focused
      on mechanisms in uranium-exposed adult animals. However, recent data on
      developing animals have shown that the developing brain is also sensitive to
      uranium. Models of uranium exposure during brain development highlight the need
      to improve our understanding of the effects of uranium. In a model in which
      uranium exposure began from the first day of gestation, we studied the
      neurobehavioral consequences as well as the progression of hippocampal
      neurogenesis in animals from dams exposed to uranium. Our results show that 2
      month-old rats exposed to uranium from gestational day 1 displayed deficits in
      special memory and a prominent depressive-like phenotype. Cell proliferation was
      not disturbed in these animals, as shown by 5-bromo-2'deoxyuridine
      (BrdU)/neuronal specific nuclear protein (NeuN) immunostaining in the dentate
      gyrus. However, in some animals, the pyramidal cell layer was dispersed in the
      CA3 region. From our previous results with the same model, the hypothesis of
      alterations of neurogenesis at prior stages of development is worth considering,
      but is probably not the only one. Therefore, further investigations are needed to
      correlate cerebral dysfunction and its underlying mechanistic pathways.

PMID- 28513544
TI  - Morphogenetically-Active Barrier Membrane for Guided Bone Regeneration, Based on
      Amorphous Polyphosphate.
AB  - We describe a novel regeneratively-active barrier membrane which consists of a
      durable electrospun poly(epsilon-caprolactone) (PCL) net covered with a
      morphogenetically-active biohybrid material composed of collagen and inorganic
      polyphosphate (polyP). The patch-like fibrous collagen structures are decorated
      with small amorphous polyP nanoparticles (50 nm) formed by precipitation of this
      energy-rich and enzyme-degradable (alkaline phosphatase) polymer in the presence
      of calcium ions. The fabricated PCL-polyP/collagen hybrid mats are characterized
      by advantageous biomechanical properties, such as enhanced flexibility and
      stretchability with almost unaltered tensile strength of the PCL net. The
      polyP/collagen material promotes the attachment and increases the
      viability/metabolic activity of human mesenchymal stem cells compared to cells
      grown on non-coated mats. The gene expression studies revealed that cells,
      growing onto polyP/collagen coated mats show a significantly (two-fold) higher
      upregulation of the steady-state-expression of the angiopoietin-2 gene used as an
      early marker for wound healing than cells cultivated onto non-coated mats. Based
      on our results we propose that amorphous polyP, stabilized onto a collagen
      matrix, might be a promising component of functionally-active barrier membranes
      for guided tissue regeneration in medicine and dentistry.

PMID- 28513545
TI  - A Study on Immersion and Presence of a Portable Hand Haptic System for Immersive
      Virtual Reality.
AB  - This paper proposes a portable hand haptic system using Leap Motion as a haptic
      interface that can be used in various virtual reality (VR) applications. The
      proposed hand haptic system was designed as an Arduino-based sensor architecture
      to enable a variety of tactile senses at low cost, and is also equipped with a
      portable wristband. As a haptic system designed for tactile feedback, the
      proposed system first identifies the left and right hands and then sends tactile
      senses (vibration and heat) to each fingertip (thumb and index finger). It is
      incorporated into a wearable band-type system, making its use easy and
      convenient. Next, hand motion is accurately captured using the sensor of the hand
      tracking system and is used for virtual object control, thus achieving
      interaction that enhances immersion. A VR application was designed with the
      purpose of testing the immersion and presence aspects of the proposed system.
      Lastly, technical and statistical tests were carried out to assess whether the
      proposed haptic system can provide a new immersive presence to users. According
      to the results of the presence questionnaire and the simulator sickness
      questionnaire, we confirmed that the proposed hand haptic system, in comparison
      to the existing interaction that uses only the hand tracking system, provided
      greater presence and a more immersive environment in the virtual reality.

PMID- 28513548
TI  - Towards System Calibration of Panoramic Laser Scanners from a Single Station.
AB  - Terrestrial laser scanner measurements suffer from systematic errors due to
      internal misalignments. The magnitude of the resulting errors in the point cloud
      in many cases exceeds the magnitude of random errors. Hence, the task of
      calibrating a laser scanner is important for applications with high accuracy
      demands. This paper primarily addresses the case of panoramic terrestrial laser
      scanners. Herein, it is proven that most of the calibration parameters can be
      estimated from a single scanner station without a need for any reference
      information. This hypothesis is confirmed through an empirical experiment, which
      was conducted in a large machine hall using a Leica Scan Station P20 panoramic
      laser scanner. The calibration approach is based on the widely used target-based
      self-calibration approach, with small modifications. A new angular
      parameterization is used in order to implicitly introduce measurements in two
      faces of the instrument and for the implementation of calibration parameters
      describing genuine mechanical misalignments. Additionally, a computationally
      preferable calibration algorithm based on the two-face measurements is
      introduced. In the end, the calibration results are discussed, highlighting all
      necessary prerequisites for the scanner calibration from a single scanner
      station.

PMID- 28513546
TI  - Edible Plants and Their Influence on the Gut Microbiome and Acne.
AB  - Acne vulgaris affects most people at some point in their lives. Due to unclear
      etiology, likely with multiple factors, targeted and low-risk treatments have yet
      to be developed. In this review, we explore the multiple causes of acne and how
      plant-based foods and supplements can control these. The proposed causative
      factors include insulin resistance, sex hormone imbalances, inflammation and
      microbial dysbiosis. There is an emerging body of work on the human gut
      microbiome and how it mediates feedback between the foods we eat and our bodies.
      The gut microbiome is also an important mediator of inflammation in the gut and
      systemically. A low-glycemic load diet, one rich in plant fibers and low in
      processed foods, has been linked to an improvement in acne, possibly through gut
      changes or attenuation of insulin levels. Though there is much interest in the
      human microbiome, there is much more unknown, especially along the gut-skin axis.
      Collectively, the evidence suggests that approaches such as plant-based foods and
      supplements may be a viable alternative to the current first line standard of
      care for moderate acne, which typically includes antibiotics. Though patient
      compliance with major dietary changes is likely much lower than with medications,
      it is a treatment avenue that warrants further study and development.

PMID- 28513547
TI  - Epigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in
      Gliomas.
AB  - High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a
      common human brain tumor with poor patient outcome. Astrocytoma demonstrates two
      known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA)
      and on alternative lengthening of telomeres (ALT). ALT is associated with lower
      tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors
      by direct mutation and epigenetic activation of the hTERT promoter is well
      established. Here, we summarize the genetic background of TMMs in non-malignant
      cells and in cancer, in addition to clinical and pathological features of
      gliomas. Furthermore, we present new evidence for epigenetic mechanisms (EMs)
      involved in regulation of ALT and TA with special emphasis on human diffuse
      gliomas as potential therapeutic drug targets. We discuss the role of TMM
      associated telomeric chromatin factors such as DNA and histone modifying enzymes
      and non-coding RNAs including microRNAs and long telomeric TERRA transcripts.

PMID- 28513549
TI  - Brain RNA-Seq Profiling of the Mucopolysaccharidosis Type II Mouse Model.
AB  - Lysosomal storage disorders (LSDs) are a group of about 50 genetic metabolic
      disorders, mainly affecting children, sharing the inability to degrade specific
      endolysosomal substrates. This results in failure of cellular functions in many
      organs, including brain that in most patients may go through progressive
      neurodegeneration. In this study, we analyzed the brain of the mouse model for
      Hunter syndrome, a LSD mostly presenting with neurological involvement. Whole
      transcriptome analysis of the cerebral cortex and
      midbrain/diencephalon/hippocampus areas was performed through RNA-seq. Genes
      known to be involved in several neurological functions showed a significant
      differential expression in the animal model for the disease compared to wild
      type. Among the pathways altered in both areas, axon guidance, calcium
      homeostasis, synapse and neuroactive ligand-receptor interaction, circadian
      rhythm, neuroinflammation and Wnt signaling were the most significant.
      Application of RNA sequencing to dissect pathogenic alterations of complex
      syndromes allows to photograph perturbations, both determining and determined by
      these disorders, which could simultaneously occur in several metabolic and
      biochemical pathways. Results also emphasize the common, altered pathways between
      neurodegenerative disorders affecting elderly and those associated with pediatric
      diseases of genetic origin, perhaps pointing out a general common course for
      neurodegeneration, independent from the primary triggering cause.

PMID- 28513550
TI  - hCG Triggering in ART: An Evolutionary Concept.
AB  - Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation
      triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially
      presented as a substitute for hCG, has led to a new era of administering GnRH
      agonist followed by hCG triggering. According to this new concept, GnRH agonist
      enables successful ovum maturation, while hCG supports the luteal phase and
      pregnancy until placental shift.

PMID- 28513552
TI  - A Two-Echelon Cooperated Routing Problem for a Ground Vehicle and Its Carried
      Unmanned Aerial Vehicle.
AB  - In this paper, a two-echelon cooperated routing problem for the ground vehicle
      (GV) and its carried unmanned aerial vehicle (UAV) is investigated, where the GV
      travels on the road network and its UAV travels in areas beyond the road to visit
      a number of targets unreached by the GV. In contrast to the classical two-echelon
      routing problem, the UAV has to launch and land on the GV frequently to change or
      charge its battery while the GV is moving on the road network. A new 0-1 integer
      programming model is developed to formulate the problem, where the constraints on
      the spatial and temporal cooperation of GV and UAV routes are included. Two
      heuristics are proposed to solve the model: the first heuristic (H1) constructs a
      complete tour for all targets and splits it by GV routes, while the second
      heuristic (H2) constructs the GV tour and assigns UAV flights to it. Random
      instances with six different sizes (25-200 targets, 12-80 rendezvous nodes) are
      used to test the algorithms. Computational results show that H1 performs slightly
      better than H2, while H2 uses less time and is more stable.

PMID- 28513551
TI  - The Regulatory Capacity of Bivalent Genes-A Theoretical Approach.
AB  - Bivalent genes are frequently associated with developmental and lineage
      specification processes. Resolving their bivalency enables fast changes in their
      expression, which potentially can trigger cell fate decisions. Here, we provide a
      theoretical model of bivalency that allows for predictions on the occurrence,
      stability and regulatory capacity of this prominent modification state. We
      suggest that bivalency enables balanced gene expression heterogeneity that
      constitutes a prerequisite of robust lineage priming in somatic stem cells.
      Moreover, we demonstrate that interactions between the histone and DNA
      methylation machineries together with the proliferation activity control the
      stability of the bivalent state and can turn it into an unmodified state. We
      suggest that deregulation of these interactions underlies cell transformation
      processes as associated with acute myeloid leukemia (AML) and provide a model of
      AML blast formation following deregulation of the Ten-eleven Translocation (TET)
      pathway.

PMID- 28513554
TI  - An Improved Model Predictive Current Controller of Switched Reluctance Machines
      Using Time-Multiplexed Current Sensor.
AB  - This paper presents a fixed-switching-frequency model predictive current
      controller using multiplexed current sensor for switched reluctance machine (SRM)
      drives. The converter was modified to distinguish currents from simultaneously
      excited phases during the sampling period. The only current sensor installed in
      the converter was time division multiplexing for phase current sampling. During
      the commutation stage, the control steps of adjacent phases were shifted so that
      sampling time was staggered. The maximum and minimum duty ratio of pulse width
      modulation (PWM) was limited to keep enough sampling time for analog-to-digital
      (A/D) conversion. Current sensor multiplexing was realized without complex
      adjustment of either driver circuit nor control algorithms, while it helps to
      reduce the cost and errors introduced in current sampling due to inconsistency
      between sensors. The proposed controller is validated by both simulation and
      experimental results with a 1.5 kW three-phase 12/8 SRM. Satisfied current
      sampling is received with little difference compared with independent phase
      current sensors for each phase. The proposed controller tracks the reference
      current profile as accurately as the model predictive current controller with
      independent phase current sensors, while having minor tracking errors compared
      with a hysteresis current controller.

PMID- 28513553
TI  - Antibacterial Activity of 7-Epiclusianone and Its Novel Copper Metal Complex on
      Streptococcus spp. Isolated from Bovine Mastitis and Their Cytotoxicity in MAC-T
      Cells.
AB  - Mastitis is an inflammation of mammary gland parenchyma that adversely affects
      bovine health and dairy production worldwide despite significant efforts to
      eradicate it. The aim of this work was to characterize the antimicrobial activity
      of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis
      fruit, its complex with copper against Streptococcus spp. isolated from bovine
      mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC
      T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with
      optical activity. Its vibrational spectrum in the infrared region showed
      absorption bands in the high-frequency region, as well as bands that can be
      attributed to the unconjugated and conjugated stretching of the free ligand. The
      complex was anhydrous. One of the tested bacterial strains was not sensitive to
      the compounds, while the other three had MIC values of 7.8 ug mL-1 and minimum
      bactericidal concentration (MBC) values between 15.6 and 31.3 ug mL-1. These two
      compounds are bacteriostatic, did not cause damage to the cell wall and, at sub
      inhibitory concentrations, did not induce bacterial adhesion. The compounds were
      not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable
      antimicrobial properties and could potentially be used in bovine mastitis
      treatment.

PMID- 28513555
TI  - Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children
      and White-Collar Workers.
AB  - OBJECTIVE: Our study aimed to investigate the nutritional vitamin D status of
      school children aged 9-15 years and white-collar workers in Zhejiang province,
      and evaluate the efficacy of low-dose-oral vitamin D supplementation in both
      populations. METHODS: We conducted a prospective controlled trial during March
      2014 to November 2015, comparing the efficacy of vitamin D supplements (400
      IU/day) with non-intervention for 18 months in school children aged 9-15 years.
      Meanwhile, a before-after study was conducted among white-collar workers for 1
      year. Serum 25(OH)D concentration was measured at baseline and after vitamin D
      supplementation, respectively. RESULTS: At the baseline, 95% of school children
      and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school
      children, no difference was observed between the intervention and control groups
      with regard to anthropometric data. Serum 25(OH)D concentrations of the school
      children intervention group, school children control group and white-collar
      workers were 12.77 +/- 3.01 ng/mL, 14.17 +/- 3.59 ng/mL and 16.58 +/- 3.66 ng/mL
      at baseline and increased to 17.34 +/- 3.78 ng/mL, 18.04 +/- 4.01 ng/mL and 17.75
      +/- 5.36 ng/mL after vitamin D supplementation, respectively. Although, after
      adjusting for potential confounders, the 400 IU oral vitamin D supplementation
      increased serum 25(OH)D concentration in school children (beta = 0.81, p =
      0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of
      vitamin D deficiency was still very high among school children (79.23% in
      intervention group and 72.38% in control group) and white-collar workers
      (76.00%). CONCLUSIONS: High prevalence of vitamin D deficiency was common in
      these two study populations. Daily doses of 400 IU oral vitamin D supplementation
      was not able to adequately increase serum 25(OH)D concentrations. A suitable
      recommendation regarding the level of vitamin D supplementation is required for
      this Chinese population.

PMID- 28513556
TI  - Microscale Quantitative Analysis of Polyhydroxybutyrate in Prokaryotes Using
      IDMS.
AB  - Poly(3-hydroxybutyrate) (PHB) is an interesting biopolymer for replacing
      petroleum-based plastics, its biological production is performed in natural and
      engineered microorganisms. Current metabolic engineering approaches rely on high
      throughput strain construction and screening. Analytical procedures have to be
      compatible with the small scale and speed of these approaches. Here, we present a
      method based on isotope dilution mass spectrometry (IDMS) and propanolysis
      extraction of poly(3-hydroxybutyrate) from an Escherichia coli strain engineered
      for PHB production. As internal standard (IS), we applied an uniformly labeled
      13C-cell suspension, of an E. coli PHB producing strain, grown on U-13C-glucose
      as C-source. This internal 13C-PHB standard enables to quantify low
      concentrations of PHB (LOD of 0.01 ug/gCDW) from several micrograms of biomass.
      With this method, a technical reproducibility of about 1.8% relative standard
      deviation is achieved. Furthermore, the internal standard is robust towards
      different sample backgrounds and dilutions. The early addition of the internal
      standard also enables higher reproducibility and increases sensitivity and
      throughput by simplified sample preparation steps.

PMID- 28513557
TI  - Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP
      2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling
      Activation.
AB  - The present study evaluated the effects of a calcium (Ca) supplement derived from
      Gallus gallus domesticus (GD) on breaking force, microarchitecture, osteogenic
      differentiation and osteoclast differentiation factor expression in vivo in Ca
      deficient ovariectomized (OVX) rats. One percent of Ca supplement significantly
      improved Ca content and bone strength of the tibia. In micro-computed tomography
      analysis, 1% Ca supplement attenuated OVX- and low Ca-associated changes in bone
      mineral density, trabecular thickness, spacing and number. Moreover, 1% Ca
      supplemented diet increased the expression of osteoblast differentiation marker
      genes, such as bone morphogenetic protein-2, Wnt3a, small mothers against
      decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin and
      collagenase-1, while it decreased the expression of osteoclast differentiation
      genes, such as thrombospondin-related anonymous protein, cathepsin K and receptor
      activator of nuclear factor kappa B. Furthermore, 1% Ca-supplemented diet
      increased the levels of phosphorylated extracellular signal-regulated kinase and
      c-Jun N-terminal kinase. The increased expression of osteoblast differentiation
      marker genes and activation of mitogen-activated protein kinase signaling were
      associated with significant increases in trabecular bone volume, which plays an
      important role in the overall skeletal strength. Our results demonstrated that 1%
      Ca supplement inhibited osteoclastogenesis, stimulated osteoblastogenesis and
      restored bone loss in OVX rats.

PMID- 28513558
TI  - From Cell to Beak: In-Vitro and In-Vivo Characterization of Chicken Bitter Taste
      Thresholds.
AB  - Bitter taste elicits an aversive reaction, and is believed to protect against
      consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein
      coupled receptors, with a species-dependent number of subtypes. Chickens
      demonstrate bitter taste sensitivity despite having only three bitter taste
      receptors-ggTas2r1, ggTas2r2 and ggTas2r7. This minimalistic bitter taste system
      in chickens was used to determine relationships between in-vitro (measured in
      heterologous systems) and in-vivo (behavioral) detection thresholds. ggTas2r
      selective ligands, nicotine (ggTas2r1), caffeine (ggTas2r2), erythromycin and (+)
      catechin (ggTas2r7), and the Tas2r-promiscuous ligand quinine (all three
      ggTas2rs) were studied. Ligands of the same receptor had different in-vivo:in
      vitro ratios, and the ggTas2r-promiscuous ligand did not exhibit lower in-vivo:in
      vitro ratios than ggTas2r-selective ligands. In-vivo thresholds were similar or
      up to two orders of magnitude higher than the in-vitro ones.

PMID- 28513559
TI  - Detecting and Discriminating Shigella sonnei Using an Aptamer-Based Fluorescent
      Biosensor Platform.
AB  - In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate
      specific aptamers against Shigella sonnei. Real-time PCR amplification and post
      SELEX experiment revealed that the selected aptmers possessed a high binding
      affinity and specificity for S. sonnei. Of the 21 aptamers tested, the C(t)
      values of the SS-3 and SS-4 aptamers (Ct = 13.89 and Ct = 12.23, respectively)
      had the lowest value compared to other aptamer candidates. The SS-3 and SS-4
      aptamers also displayed a binding affinity (KD) of 39.32 +/- 5.02 nM and 15.89 +/
      1.77 nM, respectively. An aptamer-based fluorescent biosensor assay was designed
      to detect and discriminate S. sonnei cells using a sandwich complex pair of SS-3
      and SS-4. The detection of S. sonnei by the aptamer based fluorescent biosensor
      platform consisted of three elements: (1) 5'amine-SS-4 modification in a 96-well
      type microtiter plate surface (N-oxysuccinimide, NOS) as capture probes; (2) the
      incubation with S. sonnei and test microbes in functionalized 96 assay wells in
      parallel; (3) the readout of fluorescent activity using a Cy5-labeled SS-3
      aptamer as the detector. Our platform showed a significant ability to detect and
      discriminate S. sonnei from other enteric species such as E. coli, Salmonella
      typhimurium and other Shigella species (S. flexneri, S. boydii). In this study,
      we demonstrated the feasibility of an aptamer sensor platform to detect S. sonnei
      in a variety of foods and pave the way for its use in diagnosing shigellosis
      through multiple, portable designs.

PMID- 28513561
TI  - The Effect of Physicochemical Modification on the Function of Antibodies Induced
      by Anti-Nicotine Vaccine in Mice.
AB  - Smoking remains one of the major causes of morbidity and mortality worldwide. One
      approach to assisting smoking cessation is via anti-nicotine vaccines, composed
      of nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). We
      have previously shown that the carrier, hapten, linker, hapten load, degree of
      conjugate aggregation, and presence of adducts can each influence the function
      (nicotine-binding capacity) of the antibody (Ab) induced. Herein, we extend those
      findings and show that tertiary structure is also critical to the induction of
      functional immune responses and that this can be influenced by conjugation
      conditions. We evaluated immunogenicity in mice using six lots of NIC7-CRM, a
      conjugate of 5-aminoethoxy-nicotine (Hapten 7), and a single point (glycine 52 to
      glutamic acid) mutant nontoxic form of diphtheria toxin, cross-reactive material
      197 (CRM197), which were synthesized under different reaction conditions
      resulting in conjugates with equivalent molecular characteristics (hapten load,
      aggregates, adducts), but a different tertiary structure. When tested in mice,
      better functional responses (reduced nicotine in the brain of immunized animals
      relative to non-immunized controls) were obtained with conjugates with a more
      closed structure than those with an open conformation. These studies highlight
      the need for a better understanding of the physicochemical properties of small
      molecule conjugate vaccines.

PMID- 28513560
TI  - Meta-Chirality: Fundamentals, Construction and Applications.
AB  - Chiral metamaterials represent a special type of artificial structures that
      cannot be superposed to their mirror images. Due to the lack of mirror symmetry,
      cross-coupling between electric and magnetic fields exist in chiral mediums and
      present unique electromagnetic characters of circular dichroism and optical
      activity, which provide a new opportunity to tune polarization and realize
      negative refractive index. Chiral metamaterials have attracted great attentions
      in recent years and have given rise to a series of applications in polarization
      manipulation, imaging, chemical and biological detection, and nonlinear optics.
      Here we review the fundamental theory of chiral media and analyze the
      construction principles of some typical chiral metamaterials. Then, the progress
      in extrinsic chiral metamaterials, absorbing chiral metamaterials, and
      reconfigurable chiral metamaterials are summarized. In the last section, future
      trends in chiral metamaterials and application in nonlinear optics are
      introduced.

PMID- 28513562
TI  - Effects of Growth Media on the Diversity of Culturable Fungi from Lichens.
AB  - Microscopic and molecular studies suggest that lichen symbioses contain a
      plethora of associated fungi. These are potential producers of novel bioactive
      compounds, but strains isolated on standard media usually represent only a minor
      subset of these fungi. By using various in vitro growth conditions we are able to
      modulate and extend the fraction of culturable lichen-associated fungi. We
      observed that the presence of iron, glucose, magnesium and potassium in growth
      media is essential for the successful isolation of members from different
      taxonomic groups. According to sequence data, most isolates besides the lichen
      mycobionts belong to the classes Dothideomycetes and Eurotiomycetes. With our
      approach we can further explore the hidden fungal diversity in lichens to assist
      in the search of novel compounds.

PMID- 28513563
TI  - New Glycosides from the Fruits of Nicandra physaloides.
AB  - Three new glycosides (1-3) and 15 known ones (4-18) were isolated and identified
      from the fruits of Nicandra physaloides. The structures of these compounds were
      established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4-18) were the
      first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited
      inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values
      from 26.9 to 47.5 MUM.

PMID- 28513564
TI  - Tetrodotoxin-Producing Bacteria: Detection, Distribution and Migration of the
      Toxin in Aquatic Systems.
AB  - This review is devoted to the marine bacterial producers of tetrodotoxin (TTX), a
      potent non-protein neuroparalytic toxin. In addition to the issues of the ecology
      and distribution of TTX-producing bacteria, this review examines issues relating
      to toxin migration from bacteria to TTX-bearing animals. It is shown that the
      mechanism of TTX extraction from toxin-producing bacteria to the environment
      occur through cell death, passive/active toxin excretion, or spore germination of
      spore-forming bacteria. Data on TTX microdistribution in toxic organs of TTX
      bearing animals indicate toxin migration from the digestive system to target
      organs through the transport system of the organism. The role of symbiotic
      microflora in animal toxicity is also discussed: despite low toxin production by
      bacterial strains in laboratory conditions, even minimal amounts of TTX produced
      by intestinal microflora of an animal can contribute to its toxicity. Special
      attention is paid to methods of TTX detection applicable to bacteria. Due to the
      complexity of toxin detection in TTX-producing bacteria, it is necessary to use
      several methods based on different methodological approaches. Issues crucial for
      further progress in detecting natural sources of TTX investigation are also
      considered.

PMID- 28513566
TI  - Neurophysiological Changes Induced by Chronic Toxoplasma gondii Infection.
AB  - Although the parasite Toxoplasma gondii is one of the most pervasive neurotropic
      pathogens in the world, the host-parasite interactions during CNS infection and
      the consequences of neurological infection are just beginning to be unraveled.
      The chronic stages of infection have been considered dormant, although several
      studies have found correlations of infection with an array of host behavioral
      changes. These may facilitate parasite transmission and impact neurological
      diseases. During infection, in addition to the presence of the parasites within
      neurons, host-mediated neuroimmune and hormonal responses to infection are also
      present. T. gondii induces numerous changes to host neurons during infection and
      globally alters host neurological signaling pathways, as discussed in this
      review. Understanding the neurophysiological changes in the host brain is
      imperative to understanding the parasitic mechanisms and to delineate the effects
      of this single-celled parasite on health and its contribution to neurological
      disease.

PMID- 28513567
TI  - Mental Health Service Utilization among Black Youth; Psychosocial Determinants in
      a National Sample.
AB  - Racial disparity in mental health service utilization (MHSU) persists, and youths
      are not an exception to the underutilization of services. Very limited research
      has been conducted on the determinants of MHSU among Black youth. Using a
      national sample of American Black youth, the current study investigated the
      association between demographic factors, socioeconomic status, psychiatric
      disorders, and self-rated health (SRH) on MHSU. We also tested the heterogeneity
      of the effects of SRH and psychiatric disorders based on ethnicity, gender, and
      their intersection. We used data from the National Survey of American Life
      Adolescents supplement (NSAL-A), 2003-2004. The study enrolled 1170 Black youth
      between 13 and 17 years old including 810 African Americans and 360 Caribbean
      Blacks. Age, gender, ethnicity, socioeconomic status, SRH, 12-month psychiatric
      disorders (Composite International Diagnostic Interview modified version), and
      MHSU (last year) were measured. Logistic regressions were used for data analysis.
      Ethnicity (odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.17-0.65),
      subjective socioeconomic status (OR = 1.43, 95% CI = 1.09-1.88), SRH (OR = 2.45,
      95% CI = 1.00-6.37), and psychiatric disorders (OR = 2.17, 95% CI = 1.05-4.48)
      were associated with MHSU. Age, gender, and objective socioeconomic status were
      not associated with MHSU. Gender and ethnicity did not interact with SRH and
      psychiatric disorders on MHSU. Actual and perceived need both universally
      influence Black youths' likelihood of MHSU, regardless of their ethnicity and
      gender. Ethnicity and perceived socioeconomic status also play unique roles in
      MHSU. Future research is needed to understand pathways to MHSU for Black youth
      who both have and perceive mental health needs. There is also a need to find ways
      to promote MHSU for those with a need for mental health services.

PMID- 28513568
TI  - Using UPLC-MS/MS for Characterization of Active Components in Extracts of
      Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma
      after Oral Administration.
AB  - Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large
      array of compounds, has been effectually used in health protection. A two
      dimensional liquid chromatography (2D-LC) combined with quadrupole time-of-flight
      mass spectrometry (QTOF-MS) method was firstly established to separate and
      identify chemical components in YPF. A total of 33 compounds were identified,
      including 15 constituents (flavonoids and saponins) in Astragali radix; seven
      constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and
      11 constituents (chromone and coumarins) in Saposhnikoviae radix. The
      corresponding fragmentation pathway of typical substances was investigated. Then,
      seven active constituents (astragaloside, calycosin, formononetin,
      cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol,
      and atractylenolide II) derived from three medicinal plants were chosen to
      further investigate the pharmacokinetic behavior of YPF formula using ultrahigh
      performance liquid chromatography with triple quadrupole mass spectrometry
      system. The method was sensitive, accurate and reliable. We also used the area
      under the plasma concentration-time curve from zero to infinity (AUC0-infinity)
      as weighting factor to make an integrated pharmacokinetic curve. Results show
      that the constituents of Saposhnikoviae radix have the best absorption and
      pharmacokinetic behavior and may play important role in leading to the changes of
      overall therapeutic effects of YPF. Further study is needed to confirm the
      association between them.

PMID- 28513570
TI  - A Study of the Protective Properties of Iraqi Olive Leaves against Oxidation and
      Pathogenic Bacteria in Food Applications.
AB  - There is an ancient and prodigious history of olive trees because of their
      nutritional, medicinal, and traditional uses. Intensive studies have been
      conducted on olive leaves because they have many positive and beneficial effects
      for human health. In this study, different solvents were used to examine the
      olive leaves for their antioxidant and antimicrobial activities and their
      possible food applications. The obtained results showed that the amounts of
      phenolic compounds of the olive leaf were 190.44 +/- 0.50, 173 +/- 1.72, 147.78
      +/- 0.69, and 147.50 +/- 0.05 mg gallic acid/g extracts using methanol, ethanol,
      diethyl ether, and hexanol, respectively. The statistical analysis revealed that
      there was a significant difference in the phenolic contents in terms of the used
      solvents. The stability of the olive leaves extraction was also studied and the
      results indicated that increasing the storage temperature could negatively affect
      and encourage the degradation of the phenolic compounds. Furthermore, the olive
      leaf extraction was applied to raw sheep meat slides at 0.5%, 1.5%, and 2.5%
      (w/v) in order to test its antioxidant and antimicrobial effects. The results
      obviously showed that the sample treated with 2.5% olive leaf extract had the
      significantly (p < 0.05) lowest Thiobarbituric Acid (TBA) values of 1.92 +/- 0.12
      (mg Malonaldehyde MDA/kg) throughout 12 days of cold storage. Moreover, the
      results showed that the sample, which was treated with 2.5% olive leaf extract,
      had low total bacterial count and total coliform bacteria (6.23 +/- 0.05, 5.2 +/-
      0.35 log colony forming unit (CFU)/g, respectively) among the control, 0.5%, and
      1.5% olive leaf treated samples throughout 12 days of storage. The phenolic
      extracts from the olive leaf extract had significant antioxidant and
      antimicrobial activities, which could be used as a source of potential
      antioxidant and antimicrobial agents.

PMID- 28513569
TI  - Intravenous Arginine Administration Promotes Proangiogenic Cells Mobilization and
      Attenuates Lung Injury in Mice with Polymicrobial Sepsis.
AB  - This study investigated the influence of intravenous arginine (Arg)
      administration on alteration of circulating proangiogenic cells and remote lung
      injury in a model of polymicrobial sepsis. Mice were assigned to one normal
      control group (NC) and two sepsis groups that were induced by cecal ligation and
      puncture (CLP). One of the sepsis groups was injected with saline (SS), whereas
      the other (SA) was administered with a single bolus of 300 mg Arg/kg body weight
      via the tail vein 1 h after CLP. Septic mice were sacrificed at either 24 or 48 h
      after CLP, with their blood and lung tissues collected for analysis. Results
      showed that septic groups had higher proangiogenic cells releasing factors and
      proangiogenic cells percentage in blood. Also, concentration of inflammatory
      cytokines and expression of angiopoietin (Angpt)/Tie-2 genes in lung tissues were
      upregulated. Arg administration promoted mobilization of circulating
      proangiogenic cells while it downregulated the production of inflammatory
      cytokines and expression of Angpt/Tie-2 genes in the lung. The results of this
      investigation suggested that intravenous administration of Arg shortly after the
      onset of sepsis enhanced the mobilization of circulating proangiogenic cells,
      maintained the homeostasis of the Angpt/Tie-2 axis, and attenuated remote organ
      injury in polymicrobial sepsis.

PMID- 28513572
TI  - Synthesis and Antiradical Activity of Isoquercitrin Esters with Aromatic Acids
      and Their Homologues.
AB  - Isoquercitrin, (IQ, quercetin-3-O-beta-d-glucopyranoside) is known for strong
      chemoprotectant activities. Acylation of flavonoid glucosides with carboxylic
      acids containing an aromatic ring brings entirely new properties to these
      compounds. Here, we describe the chemical and enzymatic synthesis of a series of
      IQ derivatives at the C-6". IQ benzoate, phenylacetate, phenylpropanoate and
      cinnamate were prepared from respective vinyl esters using Novozym 435 (Lipase B
      from Candida antarctica immobilized on acrylic resin). The enzymatic procedure
      gave no products with "hydroxyaromatic" acids, their vinyl esters nor with their
      benzyl-protected forms. A chemical protection/deprotection method using Steglich
      reaction yielded IQ 4-hydroxybenzoate, vanillate and gallate. In case of p
      coumaric, caffeic, and ferulic acid, the deprotection lead to the saturation of
      the double bonds at the phenylpropanoic moiety and yielded 4-hydroxy-, 3,4
      dihydroxy- and 3-methoxy-4-hydroxy-phenylpropanoates. Reducing capacity of the
      cinnamate, gallate and 4-hydroxyphenylpropanoate towards Folin-Ciocalteau reagent
      was significantly lower than that of IQ, while other derivatives displayed
      slightly better or comparable capacity. Compared to isoquercitrin, most
      derivatives were less active in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging, but they showed significantly better 2,2'-azinobis-(3
      ethylbenzothiazoline-6-sulfonic acid, ABTS) scavenging activity and were
      substantially more active in the inhibition of tert-butylhydroperoxide induced
      lipid peroxidation of rat liver microsomes. The most active compounds were the
      hydroxyphenylpropanoates.

PMID- 28513571
TI  - Fat, Sugar, and Bone Health: A Complex Relationship.
AB  - With people aging, osteoporosis is expected to increase notably. Nutritional
      status is a relatively easily-modified risk factor, associated with many chronic
      diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD),
      along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a
      primary function in bone metabolism and maintaining bone health. In Western
      nations, diets are generally high in saturated fats, however, currently, the
      nutritional patterns dominating in China continue to be high in carbohydrates
      from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose,
      glucose, or sucrose) impart a significant impact on bone structural integrity.
      Due to diet being modifiable, demonstrating the effects of nutrition on bone
      health can provide an approach for osteoporosis prevention. Most researchers have
      reported that a high-fat diet consumption is associated with bone mineral density
      (BMD) and, as bone strength diminishes, adverse microstructure changes occur in
      the cancellous bone compartment, which is involved with lipid metabolism
      modulation disorder and the alteration of the bone marrow environment, along with
      an increased inflammatory environment. Some studies, however, demonstrated that a
      high-fat diet contributes to achieving peak bone mass, along with microstructure,
      at a younger age. Contrary to these results, others have shown that a high
      fructose diet consumption leads to stronger bones with a superior
      microarchitecture than those with the intake of a high-glucose diet and, at the
      same time, research indicated that a high-fat diet usually deteriorates
      cancellous bone parameters, and that the incorporation of fructose into a high
      fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown
      both beneficial and detrimental influences on bone metabolism. Combined, these
      studies showed that nutrition exerts different effects on bone health. Thus, a
      better understanding of the regulation between dietary nutrition and bone health
      might provide a basis for the development of strategies to improve bone health by
      modifying nutritional components.

PMID- 28513573
TI  - Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative
      Stress.
AB  - The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti
      apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis
      oxidative microenvironment. We created an oxidative stress model with H2O2
      treated PDLSCs. We used real-time PCR, Western blotting, TUNEL staining,
      fluorogenic assay and transfer genetics to confirm the degree of oxidative stress
      and apoptosis as well as the function of nuclear factor-erythroid 2-related
      factor 2 (Nrf2). We demonstrated that with upregulated levels of reactive oxygen
      species (ROS) and malondialdehyde (MDA), the effect of oxidative stress was
      obvious under H2O2 treatment. Oxidative molecules were altered after the H2O2
      exposure, whereby the signaling of Nrf2 was activated with an increase in its
      downstream effectors, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1
      (NQO1) and gamma-glutamyl cysteine synthetase (gamma-GCS). Additionally, the
      apoptosis levels gradually increased with oxidative stress by the upregulation of
      caspase-9, caspase-3, Bax and c-Fos levels in addition to the downregulation of
      Bcl-2. However, there was no alterations in levels of caspase-8. The enhanced
      antioxidant effect could not mitigate the occurrence of apoptosis. Furthermore,
      Nrf2 overexpression effectively improved the anti-oxidative levels and increased
      cell proliferation. At the same time, overexpression effectively restrained TUNEL
      staining and decreased the molecular levels of caspase-9, caspase-3, Bax and c
      Fos, but not that of caspase-8. In contrast, silencing the expression of Nrf2
      levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its
      effects on regulating oxidative stress and anti-intrinsic apoptosis by the
      activation of oxidative enzymes.

PMID- 28513574
TI  - Transcriptional and Physiological Responses to Nutrient Loading on Toxin
      Formation and Photosynthesis in Microcystis Aeruginosa FACHB-905.
AB  - An important goal of understanding harmful algae blooms is to determine how
      environmental factors affect the growth and toxin formation of toxin-producing
      species. In this study, we investigated the transcriptional responses of toxin
      formation gene (mcyB) and key photosynthesis genes (psaB, psbD and rbcL) of
      Microcystis aeruginosa FACHB-905 in different nutrient loading conditions using
      real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).
      Three physio-biochemical parameters (malondialdehyde (MDA), superoxide dismutase
      (SOD) and glutathione (GSH)) were also evaluated to provide insight into the
      physiological responses of Microcystis cells. We observed an upregulation of mcyB
      gene in nutrient-deficient conditions, especially in nitrogen (N) limitation
      condition, and the transcript abundance declined after the nutrient were
      resupplied. Differently, high transcription levels were seen in phosphorus (P)
      deficient treatments for key photosynthesis genes throughout the culture period,
      while those in N-deficient cells varied with time, suggesting an adaptive
      regulation of Microsystis cells to nutrient stress. Increased contents of
      antioxidant enzymes (SOD and GSH) were seen in both N and P-deficient conditions,
      suggesting the presence of excess amount of free radical generation caused by
      nutrient stress. The amount of SOD and GSH continued to increase even after the
      nutrient was reintroduced and a strong correlation was seen between the MDA and
      enzyme activities, indicating the robust effort of rebalancing the redox system
      in Microcystis cells. Based on these transcriptional and physiological responses
      of M. aeruginosa to nutrient loading, these results could provide more insight
      into Microcystis blooms management and toxin formation regulation.

PMID- 28513575
TI  - Adding Value to Goat Meat: Biochemical and Technological Characterization of
      Autochthonous Lactic Acid Bacteria to Achieve High-Quality Fermented Sausages.
AB  - Quality and safety are important challenges in traditional fermented sausage
      technology. Consequently, the development of a tailored starter culture based on
      indigenous microbiota constitutes an interesting alternative. In the present
      study, spontaneously fermented goat meat sausages were created and analyzed using
      a physicochemical and microbiological approach. Thereafter 170 lactic acid
      bacteria (LAB) strains were isolated and preliminary characterized by phenotypic
      assays. The hygienic and technological properties, and growth and fermentative
      potential of isolates using a goat-meat-based culture medium were evaluated. All
      strains proved to have bioprotective features due to their acidogenic metabolism.
      Almost all grew optimally in meat environments. LAB isolates presented
      proteolytic activity against meat proteins and enriched amino acid contents of
      the goat-meat-based model. The most efficient strains were four different
      Lactobacillus sakei isolates, as identified by genotyping and RAPD analysis. L.
      sakei strains are proposed as optimal candidates to improve the production of
      fermented goat meat sausages, creating a new added-value fermented product.

PMID- 28513565
TI  - Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways.
AB  - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is
      commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic
      colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and
      breast cancer. Various mechanisms mediate the upregulation of EGFR activity,
      including common mutations and truncations to its extracellular domain, such as
      in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R
      and T790M mutations, or the exon 19 truncation. These EGFR aberrations over
      activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK
      ERK MAPK and AKT-PI3K-mTOR pathways. These pathways then activate many biological
      outputs that are beneficial to cancer cell proliferation, including their chronic
      initiation and progression through the cell cycle. Here, we review the molecular
      mechanisms that regulate EGFR signal transduction, including the EGFR structure
      and its mutations, ligand binding and EGFR dimerization, as well as the signaling
      pathways that lead to G1 cell cycle progression. We focus on the induction of
      CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent
      kinase inhibitor proteins (CDKi) by EGFR signaling pathways. We also discuss the
      successes and challenges of EGFR-targeted therapies, and the potential for their
      use in combination with CDK4/6 inhibitors.

PMID- 28513577
TI  - Optical determination of crystal phase in semiconductor nanocrystals.
AB  - Optical, electronic and structural properties of nanocrystals fundamentally
      derive from crystal phase. This is especially important for polymorphic II-VI,
      III-V and I-III-VI2 semiconductor materials such as cadmium selenide, which exist
      as two stable phases, cubic and hexagonal, each with distinct properties.
      However, standard crystallographic characterization through diffraction yields
      ambiguous phase signatures when nanocrystals are small or polytypic. Moreover,
      diffraction methods are low-throughput, incompatible with solution samples and
      require large sample quantities. Here we report the identification of unambiguous
      optical signatures of cubic and hexagonal phases in II-VI nanocrystals using
      absorption spectroscopy and first-principles electronic-structure theory. High
      energy spectral features allow rapid identification of phase, even in small
      nanocrystals (~2 nm), and may help predict polytypic nanocrystals from
      differential phase contributions. These theoretical and experimental insights
      provide simple and accurate optical crystallographic analysis for liquid
      dispersed nanomaterials, to improve the precision of nanocrystal engineering and
      improve our understanding of nanocrystal reactions.

PMID- 28513576
TI  - Biofilm is a Major Virulence Determinant in Bacterial Colonization of Chronic
      Skin Ulcers Independently from the Multidrug Resistant Phenotype.
AB  - Bacterial biofilm is a major factor in delayed wound healing and high levels of
      biofilm production have been repeatedly described in multidrug resistant
      organisms (MDROs). Nevertheless, a quantitative correlation between biofilm
      production and the profile of antimicrobial drug resistance in delayed wound
      healing remains to be determined. Microbial identification, antibiotic
      susceptibility and biofilm production were assessed in 135 clinical isolates from
      87 patients. Gram-negative bacteria were the most represented microorganisms
      (60.8%) with MDROs accounting for 31.8% of the total isolates. Assessment of
      biofilm production revealed that 80% of the strains were able to form biofilm. A
      comparable level of biofilm production was found with both MDRO and not-MDRO with
      no significant differences between groups. All the methicillin-resistant
      Staphylococcus aureus (MRSA) and 80% of Pseudomonas aeruginosa MDR strains were
      found as moderate/high biofilm producers. Conversely, less than 17% of Klebsiella
      pneumoniae extended-spectrum beta-lactamase (ESBL), Escherichia coli-ESBL and
      Acinetobacter baumannii were moderate/high biofilm producers. Notably, those
      strains classified as non-biofilm producers, were always associated with biofilm
      producer bacteria in polymicrobial colonization. This study shows that biofilm
      producers were present in all chronic skin ulcers, suggesting that biofilm
      represents a key virulence determinant in promoting bacterial persistence and
      chronicity of ulcerative lesions independently from the MDRO phenotype.

PMID- 28513579
TI  - Electricity from methane by reversing methanogenesis.
AB  - Given our vast methane reserves and the difficulty in transporting methane
      without substantial leaks, the conversion of methane directly into electricity
      would be beneficial. Microbial fuel cells harness electrical power from a wide
      variety of substrates through biological means; however, the greenhouse gas
      methane has not been used with much success previously as a substrate in
      microbial fuel cells to generate electrical current. Here we construct a
      synthetic consortium consisting of: (i) an engineered archaeal strain to produce
      methyl-coenzyme M reductase from unculturable anaerobic methanotrophs for
      capturing methane and secreting acetate; (ii) micro-organisms from methane
      acclimated sludge (including Paracoccus denitrificans) to facilitate electron
      transfer by providing electron shuttles (confirmed by replacing the sludge with
      humic acids), and (iii) Geobacter sulfurreducens to produce electrons from
      acetate, to create a microbial fuel cell that converts methane directly into
      significant electrical current. Notably, this methane microbial fuel cell
      operates at high Coulombic efficiency.

PMID- 28513580
TI  - Global perturbation of organic carbon cycling by river damming.
AB  - The damming of rivers represents one of the most far-reaching human modifications
      of the flows of water and associated matter from land to sea. Dam reservoirs are
      hotspots of sediment accumulation, primary productivity (P) and carbon
      mineralization (R) along the river continuum. Here we show that for the period
      1970-2030, global carbon mineralization in reservoirs exceeds carbon fixation
      (P<R); the global P/R ratio, however, varies significantly, from 0.20 to 0.58
      because of the changing age distribution of dams. We further estimate that at the
      start of the twenty-first century, in-reservoir burial plus mineralization
      eliminated 4.0+/-0.9 Tmol per year (48+/-11 Tg C per year) or 13% of total
      organic carbon (OC) carried by rivers to the oceans. Because of the ongoing boom
      in dam building, in particular in emerging economies, this value could rise to
      6.9+/-1.5 Tmol per year (83+/-18 Tg C per year) or 19% by 2030.

PMID- 28513578
TI  - Crystal structure of a multi-domain human smoothened receptor in complex with a
      super stabilizing ligand.
AB  - The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein
      coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog
      signalling pathway. Here we report the crystal structure of the multi-domain
      human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray
      free-electron laser source at 2.9 A. The structure reveals a precise arrangement
      of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge
      domain (HD) and an intact extracellular cysteine-rich domain (CRD). This
      architecture enables allosteric interactions between the domains that are
      important for ligand recognition and receptor activation. By combining the
      structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange
      analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and
      the HD play a central role in transmitting the signal employing a unique GPCR
      activation mechanism, distinct from other multi-domain GPCRs.

PMID- 28513581
TI  - Tailoring spin defects in diamond by lattice charging.
AB  - Atomic-size spin defects in solids are unique quantum systems. Most applications
      require nanometre positioning accuracy, which is typically achieved by low-energy
      ion implantation. A drawback of this technique is the significant residual
      lattice damage, which degrades the performance of spins in quantum applications.
      Here we show that the charge state of implantation-induced defects drastically
      influences the formation of lattice defects during thermal annealing. Charging of
      vacancies at, for example, nitrogen implantation sites suppresses the formation
      of vacancy complexes, resulting in tenfold-improved spin coherence times and
      twofold-improved formation yield of nitrogen-vacancy centres in diamond. This is
      achieved by confining implantation defects into the space-charge layer of free
      carriers generated by a boron-doped diamond structure. By combining these results
      with numerical calculations, we arrive at a quantitative understanding of the
      formation and dynamics of the implanted spin defects. These results could improve
      engineering of quantum devices using solid-state systems.

PMID- 28513582
TI  - Behavioural individuality in clonal fish arises despite near-identical rearing
      conditions.
AB  - Behavioural individuality is thought to be caused by differences in genes and/or
      environmental conditions. Therefore, if these sources of variation are removed,
      individuals are predicted to develop similar phenotypes lacking repeatable
      individual variation. Moreover, even among genetically identical individuals,
      direct social interactions are predicted to be a powerful factor shaping the
      development of individuality. We use tightly controlled ontogenetic experiments
      with clonal fish, the Amazon molly (Poecilia formosa), to test whether near
      identical rearing conditions and lack of social contact dampen individuality. In
      sharp contrast to our predictions, we find that (i) substantial individual
      variation in behaviour emerges among genetically identical individuals isolated
      directly after birth into highly standardized environments and (ii) increasing
      levels of social experience during ontogeny do not affect levels of individual
      behavioural variation. In contrast to the current research paradigm, which
      focuses on genes and/or environmental drivers, our findings suggest that
      individuality might be an inevitable and potentially unpredictable outcome of
      development.

PMID- 28513585
TI  - Correspondence: Flawed assumptions compromise water yield assessment.

PMID- 28513583
TI  - The cohesin-like RecN protein stimulates RecA-mediated recombinational repair of
      DNA double-strand breaks.
AB  - RecN is a cohesin-like protein involved in DNA double-strand break repair in
      bacteria. The RecA recombinase functions to mediate repair via homologous DNA
      strand invasion to form D-loops. Here we provide evidence that the RecN protein
      stimulates the DNA strand invasion step of RecA-mediated recombinational DNA
      repair. The intermolecular DNA tethering activity of RecN protein described
      previously cannot fully explain this novel activity since stimulation of RecA
      function is species-specific and requires RecN ATP hydrolysis. Further, DNA-bound
      RecA protein increases the rate of ATP hydrolysis catalysed by RecN during the
      DNA pairing reaction. DNA-dependent RecN ATPase kinetics are affected by RecA
      protein in a manner suggesting a specific order of protein-DNA assembly, with
      RecN acting after RecA binds DNA. We present a model for RecN function that
      includes presynaptic stimulation of the bacterial repair pathway perhaps by
      contributing to the RecA homology search before ternary complex formation.

PMID- 28513584
TI  - Kinesin-5-independent mitotic spindle assembly requires the antiparallel
      microtubule crosslinker Ase1 in fission yeast.
AB  - Bipolar spindle assembly requires a balance of forces where kinesin-5 produces
      outward pushing forces to antagonize the inward pulling forces from kinesin-14 or
      dynein. Accordingly, Kinesin-5 inactivation results in force imbalance leading to
      monopolar spindle and chromosome segregation failure. In fission yeast, force
      balance is restored when both kinesin-5 Cut7 and kinesin-14 Pkl1 are deleted,
      restoring spindle bipolarity. Here we show that the cut7Deltapkl1Delta spindle is
      fully competent for chromosome segregation independently of motor activity,
      except for kinesin-6 Klp9, which is required for anaphase spindle elongation. We
      demonstrate that cut7Deltapkl1Delta spindle bipolarity requires the microtubule
      antiparallel bundler PRC1/Ase1 to recruit CLASP/Cls1 to stabilize microtubules.
      Brownian dynamics-kinetic Monte Carlo simulations show that Ase1 and Cls1
      activity are sufficient for initial bipolar spindle formation. We conclude that
      pushing forces generated by microtubule polymerization are sufficient to promote
      spindle pole separation and the assembly of bipolar spindle in the absence of
      molecular motors.

PMID- 28513586
TI  - Hundreds of dual-stage antimalarial molecules discovered by a functional
      gametocyte screen.
AB  - Plasmodium falciparum stage V gametocytes are responsible for parasite
      transmission, and drugs targeting this stage are needed to support malaria
      elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the
      previously developed P. falciparum female gametocyte activation assay (Pf FGAA),
      which assesses stage V female gametocyte viability and functionality using Pfs25
      expression. We identify over 400 compounds with activities <2 MUM, chemically
      classified into 57 clusters and 33 singletons. Up to 68% of the hits are
      chemotypes described for the first time as late-stage gametocyte-targeting
      molecules. In addition, the biological profile of 90 compounds representing the
      chemical diversity is assessed. We confirm in vitro transmission-blocking
      activity of four of the six selected molecules belonging to three distinct
      scaffold clusters. Overall, this TCAMS gametocyte screen provides 276 promising
      antimalarial molecules with dual asexual/sexual activity, representing starting
      points for target identification and candidate selection.

PMID- 28513587
TI  - Experimental quantum compressed sensing for a seven-qubit system.
AB  - Well-controlled quantum devices with their increasing system size face a new
      roadblock hindering further development of quantum technologies. The effort of
      quantum tomography-the reconstruction of states and processes of a quantum device
      scales unfavourably: state-of-the-art systems can no longer be characterized.
      Quantum compressed sensing mitigates this problem by reconstructing states from
      incomplete data. Here we present an experimental implementation of compressed
      tomography of a seven-qubit system-a topological colour code prepared in a
      trapped ion architecture. We are in the highly incomplete-127 Pauli basis
      measurement settings-and highly noisy-100 repetitions each-regime. Originally,
      compressed sensing was advocated for states with few non-zero eigenvalues. We
      argue that low-rank estimates are appropriate in general since statistical noise
      enables reliable reconstruction of only the leading eigenvectors. The remaining
      eigenvectors behave consistently with a random-matrix model that carries no
      information about the true state.

PMID- 28513588
TI  - Inertial displacement of a domain wall excited by ultra-short circularly
      polarized laser pulses.
AB  - Domain wall motion driven by ultra-short laser pulses is a pre-requisite for
      envisaged low-power spintronics combining storage of information in
      magnetoelectronic devices with high speed and long distance transmission of
      information encoded in circularly polarized light. Here we demonstrate the
      conversion of the circular polarization of incident femtosecond laser pulses into
      inertial displacement of a domain wall in a ferromagnetic semiconductor. In our
      study, we combine electrical measurements and magneto-optical imaging of the
      domain wall displacement with micromagnetic simulations. The optical spin
      transfer torque acts over a picosecond recombination time of the spin-polarized
      photo-carriers that only leads to a deformation of the initial domain wall
      structure. We show that subsequent depinning and micrometre-distance displacement
      without an applied magnetic field or any other external stimuli can only occur
      due to the inertia of the domain wall.

PMID- 28513590
TI  - Giant tunnelling electroresistance in metal/ferroelectric/semiconductor tunnel
      junctions by engineering the Schottky barrier.
AB  - Recently, ferroelectric tunnel junctions have attracted much attention due to
      their potential applications in non-destructive readout non-volatile memories.
      Using a semiconductor electrode has been proven effective to enhance the
      tunnelling electroresistance in ferroelectric tunnel junctions. Here we report a
      systematic investigation on electroresistance of Pt/BaTiO3/Nb:SrTiO3
      metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky
      barrier on Nb:SrTiO3 surface via varying BaTiO3 thickness and Nb doping
      concentration. The optimum ON/OFF ratio as great as 6.0 * 106, comparable to that
      of commercial Flash memories, is achieved in a device with 0.1 wt% Nb
      concentration and a 4-unit-cell-thick BaTiO3 barrier. With this thinnest BaTiO3
      barrier, which shows a negligible resistance to the tunnelling current but is
      still ferroelectric, the device is reduced to a polarization-modulated
      metal/semiconductor Schottky junction that exhibits a more efficient control on
      the tunnelling resistance to produce the giant electroresistance observed. These
      results may facilitate the design of high performance non-volatile resistive
      memories.

PMID- 28513589
TI  - Decoding material-specific memory reprocessing during sleep in humans.
AB  - Neuronal learning activity is reactivated during sleep but the dynamics of this
      reactivation in humans are still poorly understood. Here we use multivariate
      pattern classification to decode electrical brain activity during sleep and
      determine what type of images participants had viewed in a preceding learning
      session. We find significant patterns of learning-related processing during rapid
      eye movement (REM) and non-REM (NREM) sleep, which are generalizable across
      subjects. This processing occurs in a cyclic fashion during time windows
      congruous to critical periods of synaptic plasticity. Its spatial distribution
      over the scalp and relevant frequencies differ between NREM and REM sleep.
      Moreover, only the strength of reprocessing in slow-wave sleep influenced later
      memory performance, speaking for at least two distinct underlying mechanisms
      between these states. We thus show that memory reprocessing occurs in both NREM
      and REM sleep in humans and that it pertains to different aspects of the
      consolidation process.

PMID- 28513591
TI  - Zinc is a potent and specific inhibitor of IFN-lambda3 signalling.
AB  - Lambda interferons (IFNL, IFN-lambda) are pro-inflammatory cytokines important in
      acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and
      rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance,
      as well as inflammation and fibrosis progression in viral and non-viral liver
      disease. The underlying mechanism, however, is not defined. Here we show that the
      rs12979860 CC genotype correlates with increased hepatic metallothionein
      expression through increased systemic zinc levels. Zinc interferes with IFN
      lambda3 binding to IFNL receptor 1 (IFNLR1), resulting in decreased antiviral
      activity and increased viral replication (HCV, influenza) in vitro. HCV patients
      with high zinc levels have low hepatocyte antiviral and inflammatory gene
      expression and high viral loads, confirming the inhibitory role of zinc in vivo.
      We provide the first evidence that zinc can act as a potent and specific
      inhibitor of IFN-lambda3 signalling and highlight its potential as a target of
      therapeutic intervention for IFN-lambda3-mediated chronic disease.

PMID- 28513592
TI  - IFN-gamma increases susceptibility to influenza A infection through suppression
      of group II innate lymphoid cells.
AB  - Increased levels of interferon-gamma (IFN-gamma) are routinely observed in the
      respiratory tract following influenza virus infection, yet its potential role
      remains unclear. We now demonstrate that influenza-induced IFN-gamma restricts
      protective innate lymphoid cell group II (ILC2) function in the lung following
      challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus.
      Specifically, IFN-gamma deficiency resulted in enhanced ILC2 activity,
      characterized by increased production of interleukin (IL)-5 and amphiregulin, and
      improved tissue integrity, yet no change in ILC2 numbers, viral load or
      clearance. We further found that IFN-gamma-deficient mice, as well as wild-type
      animals treated with neutralizing anti-IFN-gamma antibody, exhibited decreased
      susceptibility to lethal infection with H1N1 CA04 influenza virus, and moreover
      that survival was dependent on the presence of IL-5. The beneficial effects of
      IFN-gamma neutralization were not observed in ILC2-deficient animals. These data
      support the novel concept that IFN-gamma can have a detrimental role in the
      pathogenesis of influenza through a restriction in ILC2 activity. Thus,
      regulation of ILC2 activity is a potential target for post-infection therapy of
      influenza.

PMID- 28513593
TI  - Jak3 deficiency blocks innate lymphoid cell development.
AB  - Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive
      severe combined immunodeficiency (SCID). Defects in this form of SCID are
      restricted to the immune system, which led to the development of
      immunosuppressive JAK inhibitors. We find that the B6.Cg-Nr1d1tm1Ven/LazJ mouse
      line purchased from Jackson Laboratories harbors a spontaneous mutation in Jak3,
      generating a SCID phenotype and an inability to generate antigen-independent
      professional cytokine-producing innate lymphoid cells (ILCs). Mechanistically,
      Jak3 deficiency blocks ILC differentiation in the bone marrow at the ILC
      precursor and the pre-NK cell progenitor. We further demonstrate that the pan-JAK
      inhibitor tofacitinib and the specific JAK3 inhibitor PF-06651600 impair the
      ability of human intraepithelial ILC1 (iILC1) to produce IFN-gamma, without
      affecting ILC3 production of IL-22. Both inhibitors impaired the proliferation of
      iILC1 and ILC3 and differentiation of human ILC in vitro. Tofacitinib is
      currently approved for the treatment of moderate-to-severely active rheumatoid
      arthritis. Both tofacitinib and PF-06651600 are currently in clinical trials for
      several other immune-mediated conditions. Our data suggest that therapeutic
      inhibition of JAK may also impact ILCs and, to some extent, underlie clinical
      efficacy.

PMID- 28513594
TI  - Regionally compartmentalized resident memory T cells mediate naturally acquired
      protection against pneumococcal pneumonia.
AB  - As children age, they become less susceptible to the diverse microbes causing
      pneumonia. These microbes are pathobionts that infect the respiratory tract
      multiple times during childhood, generating immunological memory. To elucidate
      mechanisms of such naturally acquired immune protection against pneumonia, we
      modeled a relevant immunological history in mice by infecting their airways with
      mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous
      pneumococcal infections provided protection against a heterotypic, highly
      virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term
      sterilizing immunity. This protection was diminished by depletion of CD4+ cells
      prior to the final infection. The resolution of previous pneumococcal infections
      seeded the lungs with CD4+ resident memory T (TRM) cells, which responded to
      heterotypic pneumococcus stimulation by producing multiple effector cytokines,
      particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing
      CD4+ TRM cells were confined to the previously infected lobe, rather than
      dispersed throughout the lower respiratory tract. Importantly, pneumonia
      protection also was confined to that immunologically experienced lobe. Thus
      regionally localized memory cells provide superior local tissue protection to
      that mediated by systemic or central memory immune defenses. We conclude that
      respiratory bacterial infections elicit CD4+ TRM cells that fill a local niche to
      optimize heterotypic protection of the affected tissue, preventing pneumonia.

PMID- 28513595
TI  - HIV-2 infection is associated with preserved GALT homeostasis and epithelial
      integrity despite ongoing mucosal viral replication.
AB  - The mechanisms that enable preservation of gut mucosal integrity during
      persistent viral replication and inherent inflammation remain unclear. Here, we
      investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally
      occurring form of attenuated HIV disease. We found viral replication in both
      sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating
      CD4+T-cells per MUl) despite their undetectable viremia, accompanied by
      interferon-gamma-producing CD8 T-cell expansion, irrespective of antiretroviral
      treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17-
      or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing
      innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were
      maintained. In agreement, the epithelium histology was preserved, including tight
      junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection
      of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1
      expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were
      significantly increased, in direct correlation with GM-CSF, indicating a local
      response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of
      mucosal integrity in HIV-2 infection was associated with T-cell recruitment
      responses, potentially counteracting CD4 T-cell depletion due to HIV-2
      replication. These data have unique implications for the design of therapies
      targeting gut homeostasis in HIV-1 infection and other chronic inflammatory
      settings.

PMID- 28513596
TI  - An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection.
AB  - The airway epithelium secretes proteins that function in innate defense against
      infection. Bactericidal/permeability-increasing fold-containing family member A1
      (BPIFA1) is secreted into airways and has a protective role during bacterial
      infections, but it is not known whether it also has an antiviral role. To
      determine a role in host defense against influenza A virus (IAV) infection and to
      find the underlying defense mechanism, we developed transgenic mouse models that
      are deficient in BPIFA1 and used these, in combination with in vitro three
      dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its
      antiviral properties. We show that BPIFA1 has a significant role in mucosal
      defense against IAV infection. BPIFA1 secretion was highly modulated after IAV
      infection. Mice deficient in BPIFA1 lost more weight after infection, supported a
      higher viral load and virus reached the peripheral lung earlier, indicative of a
      defect in the control of infection. Further analysis using mTEC cultures showed
      that BPIFA1-deficient cells bound more virus particles, displayed increased
      nuclear import of IAV ribonucleoprotein complexes, and supported higher levels of
      viral replication. Our results identify a critical role of BPIFA1 in the initial
      phase of infection by inhibiting the binding and entry of IAV into airway
      epithelial cells.

PMID- 28513597
TI  - Thermophoretic migration of vesicles depends on mean temperature and head group
      chemistry.
AB  - A number of colloidal systems, including polymers, proteins, micelles and hard
      spheres, have been studied in thermal gradients to observe and characterize their
      driven motion. Here we show experimentally the thermophoretic behaviour of
      unilamellar lipid vesicles, finding that mobility depends on the mean local
      temperature of the suspension and on the structure of the exposed polar lipid
      head groups. By tuning the temperature, vesicles can be directed towards hot or
      cold, forming a highly concentrated region. Binary mixtures of vesicles composed
      of different lipids can be segregated using thermophoresis, according to their
      head group. Our results demonstrate that thermophoresis enables robust and
      chemically specific directed motion of liposomes, which can be exploited in
      driven processes.

PMID- 28513599
TI  - Corrigendum: Arctic megaslide at presumed rest.

PMID- 28513598
TI  - YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell
      fate.
AB  - How the behaviour of somatic stem cells (SCs) is influenced by mechanical signals
      remains a black-box in cell biology. Here we show that YAP/TAZ regulation by cell
      shape and rigidity of the extracellular matrix (ECM) dictates a pivotal SC
      decision: to remain undifferentiated and grow, or to activate a terminal
      differentiation programme. Notably, mechano-activation of YAP/TAZ promotes
      epidermal stemness by inhibition of Notch signalling, a key factor for epidermal
      differentiation. Conversely, YAP/TAZ inhibition by low mechanical forces induces
      Notch signalling and loss of SC traits. As such, mechano-dependent regulation of
      YAP/TAZ reflects into mechano-dependent regulation of Notch signalling.
      Mechanistically, at least in part, this is mediated by YAP/TAZ binding to distant
      enhancers activating the expression of Delta-like ligands, serving as 'in cis'
      inhibitors of Notch. Thus YAP/TAZ mechanotransduction integrates with cell-cell
      communication pathways for fine-grained orchestration of SC decisions.

PMID- 28513601
TI  - Vacuum ultraviolet spectroscopy of the lowest-lying electronic state in
      subcritical and supercritical water.
AB  - The nature and extent of hydrogen bonding in water has been scrutinized for
      decades, including how it manifests in optical properties. Here we report vacuum
      ultraviolet absorption spectra for the lowest-lying electronic state of
      subcritical and supercritical water. For subcritical water, the spectrum
      redshifts considerably with increasing temperature, demonstrating the gradual
      breakdown of the hydrogen-bond network. Tuning the density at 381  degrees C
      gives insight into the extent of hydrogen bonding in supercritical water. The
      known gas-phase spectrum, including its vibronic structure, is duplicated in the
      low-density limit. With increasing density, the spectrum blueshifts and the
      vibronic structure is quenched as the water monomer becomes electronically
      perturbed. Fits to the supercritical water spectra demonstrate consistency with
      dimer/trimer fractions calculated from the water virial equation of state and
      equilibrium constants. Using the known water dimer interaction potential, we
      estimate the critical distance between molecules (ca. 4.5 A) needed to explain
      the vibronic structure quenching.

PMID- 28513600
TI  - Temporal dynamics of gene expression and histone marks at the Arabidopsis shoot
      meristem during flowering.
AB  - Plants can produce organs throughout their entire life from pluripotent stem
      cells located at their growing tip, the shoot apical meristem (SAM). At the time
      of flowering, the SAM of Arabidopsis thaliana switches fate and starts producing
      flowers instead of leaves. Correct timing of flowering in part determines
      reproductive success, and is therefore under environmental and endogenous
      control. How epigenetic regulation contributes to the floral transition has
      eluded analysis so far, mostly because of the poor accessibility of the SAM. Here
      we report the temporal dynamics of the chromatin modifications H3K4me3 and
      H3K27me3 and their correlation with transcriptional changes at the SAM in
      response to photoperiod-induced flowering. Emphasizing the importance of tissue
      specific epigenomic analyses we detect enrichments of chromatin states in the SAM
      that were not apparent in whole seedlings. Furthermore, our results suggest that
      regulation of translation might be involved in adjusting meristem function during
      the induction of flowering.

PMID- 28513603
TI  - Enhanced heterogeneous ice nucleation by special surface geometry.
AB  - The freezing of water typically proceeds through impurity-mediated heterogeneous
      nucleation. Although non-planar geometry generically exists on the surfaces of
      ice nucleation centres, its role in nucleation remains poorly understood. Here we
      show that an atomically sharp, concave wedge can further promote ice nucleation
      with special wedge geometries. Our molecular analysis shows that significant
      enhancements of ice nucleation can emerge both when the geometry of a wedge
      matches the ice lattice and when such lattice match does not exist. In
      particular, a 45 degrees  wedge is found to greatly enhance ice nucleation by
      facilitating the formation of special topological defects that consequently
      catalyse the growth of regular ice. Our study not only highlights the active role
      of defects in nucleation but also suggests that the traditional concept of
      lattice match between a nucleation centre and crystalline lattice should be
      extended to include a broader match with metastable, non-crystalline structural
      motifs.

PMID- 28513602
TI  - Tetrahelical structural family adopted by AGCGA-rich regulatory DNA regions.
AB  - Here we describe AGCGA-quadruplexes, an unexpected addition to the well-known
      tetrahelical families, G-quadruplexes and i-motifs, that have been a focus of
      intense research due to their potential biological impact in G- and C-rich DNA
      regions, respectively. High-resolution structures determined by solution-state
      nuclear magnetic resonance (NMR) spectroscopy demonstrate that AGCGA-quadruplexes
      comprise four 5'-AGCGA-3' tracts and are stabilized by G-A and G-C base pairs
      forming GAGA- and GCGC-quartets, respectively. Residues in the core of the
      structure are connected with edge-type loops. Sequences of alternating 5'-AGCGA
      3' and 5'-GGG-3' repeats could be expected to form G-quadruplexes, but are shown
      herein to form AGCGA-quadruplexes instead. Unique structural features of AGCGA
      quadruplexes together with lower sensitivity to cation and pH variation imply
      their potential biological relevance in regulatory regions of genes responsible
      for basic cellular processes that are related to neurological disorders, cancer
      and abnormalities in bone and cartilage development.

PMID- 28513604
TI  - Exploring the statistical uncertainty in acceptable exposure limit values for
      hexavalent chromium exposure.
AB  - Exposure limit values give the exposure level at which an accepted (or
      acceptable) number of additional work related diseases are expected. The values
      are derived from dose-response curves and carry a large amount of uncertainty. In
      this paper we aim to quantify some of this uncertainty with statistical means. We
      explore the limit value issued by the European Chemical Agency (ECHA) for
      occupational exposure to hexavalent chromium, CR(VI). We investigate how the dose
      response model and statistical estimation variability influences the data-based
      fixation of exposure limit values. We also look at the effect of measurement
      variation on the exposure level itself, where simulation techniques allow to
      quantify the uncertainty in statistical terms. We demonstrate that statistical
      uncertainty needs to be taken into account when fixing exposure limit values
      based on data.

PMID- 28513605
TI  - Picocyanobacteria and deep-ocean fluorescent dissolved organic matter share
      similar optical properties.
AB  - Marine chromophoric dissolved organic matter (CDOM) and its related fluorescent
      components (FDOM), which are widely distributed but highly photobleached in the
      surface ocean, are critical in regulating light attenuation in the ocean.
      However, the origins of marine FDOM are still under investigation. Here we show
      that cultured picocyanobacteria, Synechococcus and Prochlorococcus, release FDOM
      that closely match the typical fluorescent signals found in oceanic environments.
      Picocyanobacterial FDOM also shows comparable apparent fluorescent quantum yields
      and undergoes similar photo-degradation behaviour when compared with deep-ocean
      FDOM, further strengthening the similarity between them. Ultrahigh-resolution
      mass spectrometry (MS) and nuclear magnetic resonance spectroscopy reveal
      abundant nitrogen-containing compounds in Synechococcus DOM, which may originate
      from degradation products of the fluorescent phycobilin pigments. Given the
      importance of picocyanobacteria in the global carbon cycle, our results indicate
      that picocyanobacteria are likely to be important sources of marine autochthonous
      FDOM, which may accumulate in the deep ocean.

PMID- 28513606
TI  - Corrigendum: Risk Model for Colorectal Cancer in Spanish Population Using
      Environmental and Genetic Factors: Results from the MCC-Spain study.

PMID- 28513608
TI  - The last sea nomads of the Indonesian archipelago: genomic origins and dispersal.
AB  - The Bajo, the world's largest remaining sea nomad group, are scattered across
      hundreds of recently settled communities in Island Southeast Asia, along the
      coasts of Indonesia, Malaysia and the Philippines. With a significant role in
      historical trading, the Bajo lived until recently as nomads, spending their
      entire lives on houseboats while moving long distances to fish and trade. Along
      the routes they traveled, the Bajo settled and intermarried with local land-based
      groups, leading to 'maritime creolization', a process whereby Bajo communities
      retained their culture, but assimilated - and frequently married into - local
      groups. The origins of the Bajo have remained unclear despite several hypotheses
      from oral tradition, culture and language, all currently without supporting
      genetic evidence. Here, we report genome-wide SNP analyses on 73 Bajo individuals
      from three communities across Indonesia - the Derawan of Northeast Borneo, the
      Kotabaru of Southeast Borneo and the Kendari of Southeast Sulawesi, with 87 new
      samples from three populations surrounding the area where these Bajo peoples
      live. The Bajo likely share a common connection with Southern Sulawesi, but
      crucially, each Bajo community also exhibits unique genetic contributions from
      neighboring populations.

PMID- 28513607
TI  - Variants in TTC25 affect autistic trait in patients with autism spectrum disorder
      and general population.
AB  - Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder
      with a complex genetic architecture. To identify genetic variants underlying ASD,
      we performed single-variant and gene-based genome-wide association studies using
      a dense genotyping array containing over 2.3 million single-nucleotide variants
      in a discovery sample of 160 families with at least one child affected with non
      syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic
      trait. Replication of the top findings was performed in Psychiatric Genomics
      Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association
      of quantitative autistic trait was observed with the TTC25 gene at 17q21.2
      (effect size=10.2, P-value=3.4 * 10-7) in the gene-based analysis. The gene also
      showed nominally significant association in the cohort-based ERF study
      (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved
      the association signal (P-valuemeta=1.5 * 10-8). No genome-wide significant
      signal was observed in the single-variant analysis of either the binary ASD
      phenotype or the quantitative autistic trait. Our study has identified a novel
      gene TTC25 to be associated with quantitative autistic trait in patients with
      ASD. The replication of association in a cohort-based study and the effect
      estimate suggest that variants in TTC25 may also be relevant for broader ASD
      phenotype in the general population. TTC25 is overexpressed in frontal cortex and
      testis and is known to be involved in cilium movement and thus an interesting
      candidate gene for autistic trait.

PMID- 28513610
TI  - Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus
      callosum dysgenesis, ptosis, and developmental delay.
AB  - The introduction of whole-exome sequencing into the Pediatric Genetics clinic has
      increased the identification of novel genes associated with neurodevelopmental
      disorders and congenital anomalies. This agnostic approach has shed light on
      multiple proteins and pathways not previously known to be associated with
      disease. Here we report eight subjects from six families with predicted loss of
      function variants in ZNF462, a zinc-finger protein of unknown function. These
      individuals have overlapping phenotypes that include ptosis, metopic ridging,
      craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. We
      propose that ZNF462 plays an important role in embryonic development, and is
      associated with craniofacial and neurodevelopmental abnormalities.

PMID- 28513609
TI  - Application of rare variant transmission disequilibrium tests to epileptic
      encephalopathy trio sequence data.
AB  - The classic epileptic encephalopathies, including infantile spasms (IS) and
      Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise
      sporadically. De novo variants in genes mainly encoding ion channel and synaptic
      proteins have been found to account for over 15% of patients with IS or LGS. The
      contribution of autosomal recessive genetic variation, however, is less well
      understood. We implemented a rare variant transmission disequilibrium test (TDT)
      to search for autosomal recessive epileptic encephalopathy genes in a cohort of
      320 outbred patient-parent trios that were generally prescreened for rare
      metabolic disorders. In the current sample, our rare variant transmission
      disequilibrium test did not identify individual genes with significantly
      distorted transmission over expectation after correcting for the multiple tests.
      While the rare variant transmission disequilibrium test did not find evidence of
      a role for individual autosomal recessive genes, our current sample is
      insufficiently powered to assess the overall role of autosomal recessive
      genotypes in an outbred epileptic encephalopathy population.

PMID- 28513611
TI  - Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2
      variants.
AB  - Variation in FOXC1 and PITX2 is associated with Axenfeld-Rieger syndrome,
      characterised by structural defects of the anterior chamber of the eye and a
      range of systemic features. Approximately half of all affected individuals will
      develop glaucoma, but the age at diagnosis and the phenotypic spectrum have not
      been well defined. As phenotypic heterogeneity is common, we aimed to delineate
      the age-related penetrance and the full phenotypic spectrum of glaucoma in FOXC1
      or PITX2 carriers recruited through a national disease registry. All coding exons
      of FOXC1 and PITX2 were directly sequenced and multiplex ligation-dependent probe
      amplification was performed to detect copy number variation. The cohort included
      53 individuals from 24 families with disease-associated FOXC1 or PITX2 variants,
      including one individual diagnosed with primary congenital glaucoma and five with
      primary open-angle glaucoma. The overall prevalence of glaucoma was 58.5% and was
      similar for both genes (53.3% for FOXC1 vs 60.9% for PITX2, P=0.59), however, the
      median age at glaucoma diagnosis was significantly lower in FOXC1 (6.0+/-13.0
      years) compared with PITX2 carriers (18.0+/-10.6 years, P=0.04). The penetrance
      at 10 years old was significantly lower in PITX2 than FOXC1 carriers (13.0% vs
      42.9%, P=0.03) but became comparable at 25 years old (71.4% vs 57.7%, P=0.38).
      These findings have important implications for the genetic counselling of
      families affected by Axenfeld-Rieger syndrome, and also suggest that FOXC1 and
      PITX2 contribute to the genetic architecture of primary glaucoma subtypes.

PMID- 28513612
TI  - Insertion of Alu elements at a PTEN hotspot in Cowden syndrome.
AB  - Cowden syndrome (CS) is an inherited autosomal dominant disorder associated with
      germline pathogenic variants of the PTEN tumor suppressor gene. Its phenotypical
      expression is highly variable and the existence of patients with a CS suggestive
      phenotype without pathogenic PTEN variant may be related to genetic
      heterogeneity. In order to explore this hypothesis through the detection of
      potentially deleterious variants enabling us to identify a new candidate gene, we
      performed whole-exome sequencing (WES) in a series of 22 CS patients without
      detectable PTEN pathogenic variant using conventional methods for mutation
      screening. We failed to identify a novel candidate gene, but interestingly in two
      patients WES revealed the presence of two distinct, previously undescribed Alu
      insertions with the same break points in exon 5. These insertions were not found
      in a series of 35 breast carcinomas that showed a loss of PTEN expression without
      a detectable alteration of this gene. This study reveals the presence of a PTEN
      Alu insertion hotspot involved in CS, and suggests that undetected PTEN
      pathogenic variants could contribute to CS.

PMID- 28513613
TI  - Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis
      imperfecta.
AB  - We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T,
      p.(P249L)) in ACPT, the gene encoding acid phosphatase, testicular, which
      segregates with hypoplastic amelogenesis imperfecta in two unrelated families.
      ACPT is reported to play a role in odontoblast differentiation and mineralisation
      by supplying phosphate during dentine formation. Analysis by computerised
      tomography and scanning electron microscopy of a primary molar tooth from an
      individual homozygous for the c.746C>T variant revealed an enamel layer that was
      hypoplastic, but mineralised with prismatic architecture. These findings
      implicate variants in ACPT as a cause of early failure of amelogenesis during the
      secretory phase.

PMID- 28513614
TI  - Recurrent somatic JAK-STAT pathway variants within a RUNX1-mutated pedigree.
AB  - Germline variants within the transcription factor RUNX1 are associated with
      familial platelet disorder and acute leukemia in over 40% of carriers. At
      present, the somatic events triggering leukemic transformation appear
      heterogeneous and profiles of leukemia initiation across family members are
      poorly defined. We report a new RUNX1 family where three sisters harboring a
      germline nonsense RUNX1 variant, c.601C>T (p.(Arg201*)), developed acute
      myelomonocytic leukemia (AML) at 5 years of age. Whole-exome sequencing of tumor
      samples revealed all three siblings independently acquired variants within the
      JAK-STAT pathway, specifically targeting JAK2 and SH2B3 (a negative regulator of
      JAK2), while also sharing the 46/1 haplotype linked with sporadic JAK2-positive
      myeloproliferative neoplasms. In-depth chromosomal characterization of tumors
      revealed acquired copy number gains and uniparental disomy amplifying RUNX1, JAK2
      and SH2B3 variants, highlighting the significance of co-operation between these
      disrupted pathways. One sibling, presenting with myelodysplasia at 14 years, had
      no evidence of clonal or subclonal JAK2 or SH2B3 variants, suggesting the latter
      were specifically associated with leukemic transformation in her sisters.
      Collectively, the clinical and molecular homogeneity across these three young
      siblings provides the first notable example of convergent AML evolution in a
      RUNX1 pedigree, with the recurrent acquisition of JAK-STAT pathway variants
      giving rise to high-risk AML, characterized by chemotherapy resistance and
      relapse.

PMID- 28513616
TI  - Complementarity between medical geneticists and genetic counsellors: its added
      value in genetic services in Europe.
AB  - Clinical genetic services have progressed significantly the last few decades.
      This has led to the need for non-medical health-care professionals working as
      genetic counsellors in Europe and worldwide. However, there is no unified
      approach to genetic counsellors' role in health-care services in Europe, as in
      most countries the profession is still emerging and the educational backgrounds
      diverge noticeably, within and between countries. This qualitative study aims to
      describe the potential added value of genetic counsellors in clinical genetics
      teams and to explore their tasks and responsibilities in different European
      countries. A total of 143 participants providing genetic counselling in Europe at
      the time of the survey responded. The results show differences in activities of
      genetic counsellors, although there is a wide range of roles, which are similar.
      The ability to establish a quality relationship with consultands was frequently
      mentioned as one of the strengths of genetic counsellors, as well as a patient
      centred approach. It is believed that genetic counsellors add a more holistic
      approach of psychosocial and familial dimensions of genetic concerns to the
      multidisciplinary teams. This study provides examples of successful integration
      of genetic counsellors in teams, as complementariness with medical geneticist
      became clear in several cases. Although the added value of genetic counsellors
      was manifested, professional recognition of genetic counsellors across Europe is
      still needed in order to support the quality of patients care and safety of
      practice.

PMID- 28513615
TI  - Exome sequencing of two Italian pedigrees with non-isolated Chiari malformation
      type I reveals candidate genes for cranio-facial development.
AB  - Chiari malformation type I (CMI) is a congenital abnormality of the cranio
      cerebral junction with an estimated incidence of 1 in 1280. CMI is characterized
      by underdevelopment of the occipital bone and posterior fossa (PF) and consequent
      cerebellar tonsil herniation. The presence for a genetic basis to CMI is
      supported by many lines of evidence. The cellular and molecular mechanisms
      leading to CM1 are poorly understood. The occipital bone formation is dependent
      on complex interactions between genes and molecules with pathologies resulting
      from disruption of this delicate process. Whole-exome sequencing of affected and
      not affected individuals from two Italian families with non-isolated CMI was
      undertaken. Single-nucleotide and short insertion-deletion variants were
      prioritized using KGGSeq knowledge-based platform. We identified three
      heterozygous missense variants: DKK1 c.121G>A (p.(A41T)) in the first family, and
      the LRP4 c.2552C>G (p.(T851R)) and BMP1 c.941G>A (p.(R314H)) in the second
      family. The variants were located at highly conserved residues, segregated with
      the disease, but they were not observed in 100 unaffected in-house controls. DKK1
      encodes for a potent soluble WNT inhibitor that binds to LRP5 and LRP6, and is
      itself regulated by bone morphogenetic proteins (BMPs). DKK1 is required for
      embryonic head development and patterning. LRP4 is a novel osteoblast expressed
      receptor for DKK1 and a WNT and BMP 4 pathways integrator. Screening of DKK1 in a
      cohort of 65 CMI sporadic patients identified another missense variant, the
      c.359G>T (p.(R120L)), in two unrelated patients. These findings implicated the
      WNT signaling in the correct development of the cranial mesenchyme originating
      the PF.

PMID- 28513618
TI  - Age Increases Monocyte Adhesion on Collagen.
AB  - Adhesion of monocytes to micro-injuries on arterial walls is an important early
      step in the occurrence and development of degenerative atherosclerotic lesions.
      At these injuries, collagen is exposed to the blood stream. We are interested
      whether age influences monocyte adhesion to collagen under flow, and hence
      influences the susceptibility to arteriosclerotic lesions. Therefore, we studied
      adhesion and rolling of human peripheral blood monocytes from old and young
      individuals on collagen type I coated surface under shear flow. We find that firm
      adhesion of monocytes to collagen type I is elevated in old individuals. Pre
      stimulation by lipopolysaccharide increases the firm adhesion of monocytes
      homogeneously in older individuals, but heterogeneously in young individuals.
      Blocking integrin alphax showed that adhesion of monocytes to collagen type I is
      specific to the main collagen binding integrin alphaxbeta2. Surprisingly, we find
      no significant age-dependent difference in gene expression of integrin alphax or
      integrin beta2. However, if all integrins are activated from the outside, no
      differences exist between the age groups. Altered integrin activation therefore
      causes the increased adhesion. Our results show that the basal increase in
      integrin activation in monocytes from old individuals increases monocyte adhesion
      to collagen and therefore the risk for arteriosclerotic plaques.

PMID- 28513619
TI  - Corrigendum: A brain-sparing diphtheria toxin for chemical genetic ablation of
      peripheral cell lineages.

PMID- 28513617
TI  - The perceived impact of the European registration system for genetic counsellors
      and nurses.
AB  - The aim of the European Board of Medical Genetics has been to develop and promote
      academic and professional standards necessary in order to provide competent
      genetic counselling services. The aim of this study was to explore the impact of
      the European registration system for genetic nurses and counsellors from the
      perspectives of those professionals who have registered. Registration system was
      launched in 2013. A cross-sectional, online survey was used to explore the
      motivations and experiences of those applying for, and the effect of registration
      on their career. Fifty-five Genetic Nurses and Counsellors are registered till
      now, from them, thirty-three agreed to participate on this study. The main
      motivations for registering were for recognition of their work value and
      competence (30.3%); due to the absence of a registration system in their own
      country (15.2%) and the possibility of obtaining a European/international
      certification (27.3%), while 27.3% of respondents registered to support
      recognition of the genetic counselling profession. Some participants valued the
      registration process as an educational activity in its own right, while the
      majority indicated the greatest impact of the registration process was on their
      clinical practice. The results confirm that registrants value the opportunity to
      both confirm their own competence and advance the genetic counselling profession
      in Europe.

PMID- 28513620
TI  - Efficient hydrogen production on MoNi4 electrocatalysts with fast water
      dissociation kinetics.
AB  - Various platinum-free electrocatalysts have been explored for hydrogen evolution
      reaction in acidic solutions. However, in economical water-alkali electrolysers,
      sluggish water dissociation kinetics (Volmer step) on platinum-free
      electrocatalysts results in poor hydrogen-production activities. Here we report a
      MoNi4 electrocatalyst supported by MoO2 cuboids on nickel foam (MoNi4/MoO2@Ni),
      which is constructed by controlling the outward diffusion of nickel atoms on
      annealing precursor NiMoO4 cuboids on nickel foam. Experimental and theoretical
      results confirm that a rapid Tafel-step-decided hydrogen evolution proceeds on
      MoNi4 electrocatalyst. As a result, the MoNi4 electrocatalyst exhibits zero onset
      overpotential, an overpotential of 15 mV at 10 mA cm-2 and a low Tafel slope of
      30 mV per decade in 1 M potassium hydroxide electrolyte, which are comparable to
      the results for platinum and superior to those for state-of-the-art platinum-free
      electrocatalysts. Benefiting from its scalable preparation and stability, the
      MoNi4 electrocatalyst is promising for practical water-alkali electrolysers.

PMID- 28513623
TI  - Prevalence of malnutrition in a cohort of 509 patients with acute hip fracture:
      the importance of a comprehensive assessment.
AB  - : Backgrounds/objectives:Malnutrition is very common in acute hip fracture (HF)
      patients. Studies differ widely in their findings, with reported prevalences
      between 31 and 88% mainly because of small sample sizes and the use of different
      criteria. The aim of this study was to learn the prevalence of malnutrition in a
      large cohort of HF patients in an comprehensive way that includes the frequency
      of protein-energy malnutrition, vitamin D deficiency and sarcopenia.
      SUBJECTS/METHODS: A 1-year consecutive sample of patients admitted with fragility
      HF in a 1300-bed public University Hospital, who were assessed within the first
      72 h of admission. Clinical, functional, cognitive and laboratory variables were
      included. Energy malnutrition (body mass index (BMI) <22 kg/m2), protein
      malnutrition (serum total protein <6.5 g/dl or albumin <3.5 g/dl), vitamin D
      deficiency (serum 25-OH-vitamin D <30 ng/dl) and sarcopenia (low muscle mass plus
      low grip strength) were considered. RESULTS: Five hundred nine HF patients were
      included. The mean age was 85.6+/-6.9 years and 79.2% were women. Ninety-nine
      (20.1%) patients had a BMI <22 kg/m2. Four hundred nine patients (81.2%) had
      protein malnutrition. Eighty-seven (17.1%) patients had both energy and protein
      malnutrition. Serum vitamin D was <30 ng/ml in 466 (93%) patients. The prevalence
      of sarcopenia was 17.1%. CONCLUSIONS: Protein malnutrition and vitamin D
      deficiency are the rule in acute HF patients. Energy malnutrition and sarcopenia
      are also common. A nutritional assessment in these patients should include these
      aspects together.

PMID- 28513621
TI  - Body mass index and mortality in lung cancer patients: a systematic review and
      meta-analysis.
AB  - Studies examining the relation of body mass index (BMI) and mortality in patients
      with lung cancer have shown diverse results. We conducted a meta-analysis to
      investigate the association using all available studies from January 1982 to
      October 2016. PubMed and EMBASE were searched to identify relevant studies. We
      calculated the summary hazard ratio (HR) and 95% confidence interval (CI) using
      random effects model. The dose-response relationship was assessed by random
      effects meta-regression model. Fifty-five articles from 51 studies involving 3
      152 552 subjects (males, 54.8%) were included. The pooled results suggested that
      on average a high BMI decreased risk of death from lung cancer or all-cause. Each
      5 kg/m2 increase in BMI had a 12% lower risk of lung cancer-specific mortality
      (HR=0.88, 95% CI: 0.75-1.02, P=0.09) and a 14% lower risk of all-cause mortality
      (HR=0.86, 95% CI: 0.77-0.96, P<0.01). When stratifying by ethnicity, each 5 kg/m2
      increase in BMI was associated with 22% and 28% reduction, respectively, in the
      risk of lung cancer-specific mortality (P<0.01) and all-cause mortality (P<0.01)
      in Asians, but no association was found in Westerners (P=0.51 and P=0.53,
      respectively). In conclusion, lung cancer patients with a higher BMI have a
      longer survival than those with a lower BMI. Considering the significant
      heterogeneity between included studies, future studies are needed to confirm
      these findings.

PMID- 28513622
TI  - Human milk insulin is related to maternal plasma insulin and BMI: but other
      components of human milk do not differ by BMI.
AB  - BACKGROUND/OBJECTIVES: The impact of maternal BMI and insulin sensitivity on
      bioactive components of human milk (HM) is not well understood. As the prevalence
      of obesity and diabetes rises, it is increasingly critical that we understand how
      maternal BMI and hormones associated with metabolic disease relate to
      concentrations of bioactive components in HM. SUBJECTS/METHODS: This longitudinal
      cohort design followed 48 breastfeeding mothers through the first four months of
      lactation, collecting fasting morning HM samples at 2-weeks and 1, 2, 3 and 4
      months, and fasting maternal blood at 2-weeks and 4-months. Insulin, glucose,
      adipokines leptin and adiponectin, appetite regulating hormone ghrelin, marker of
      oxidative stress 8OHdG and inflammatory cytokines (IL-6, IL-8, and TNF-a) were
      measured in HM and maternal plasma. RESULTS: A total of 26 normal weight (NW)
      (BMI=21.4+/-2.0 kg/m2) and 22 overweight/obese (OW/Ob) (BMI=30.4+/-4.2 kg/m2)
      were followed. Of all HM analytes measured, only insulin and leptin were
      different between groups - consistently higher in the OW/Ob group (leptin:
      P<0.001; insulin: P<0.03). HM insulin was 98% higher than maternal plasma insulin
      at 2-weeks and 32% higher at 4-months (P<0.001). Maternal fasting plasma insulin
      and HOMA-IR were positively related to HM insulin at 2-weeks (P<0.001, R2?0.38,
      n=31), and 4-months (P?0.005, R2?0.20, n=38). CONCLUSIONS: The concentrations of
      insulin in HM are higher than in maternal plasma and are related to maternal BMI
      and insulin sensitivity. With the exception of leptin, there were minimal other
      differences observed in HM composition across a wide range in maternal BMI.

PMID- 28513624
TI  - Type 2 diabetes mellitus in Malaysia: current trends and risk factors.
AB  - This review discussed the prevalence of diabetes mellitus (DM) in Malaysia and
      the associated major risk factors, namely overweight/obesity, dietary practices
      and physical activity in both adults and school children. Detailed analyses of
      such information will provide crucial information for the formulation and
      implementation of programmes for the control and prevention of T2DM in the
      country. National studies from 1996-2015, and other recent nation-wide studies
      were referred to. The current prevalence of DM in 2015 is 17.5%, over double
      since 1996. Females, older age group, Indians, and urban residents had the
      highest risk of DM. The combined prevalence of overweight/obesity in 2015 is
      47.7% for adults. Adults did not achieve the recommended intakes for majority of
      the foods groups in the Malaysian Food Pyramid especially fruits and vegetables.
      Adults also had moderate physical activity level. Three nation-wide studies
      showed a prevalence ranging from 27 to 31% for combined overweight/obesity in
      school children. The prevalence was higher among boys, primary school age, Indian
      ethnicity, and even rural children are not spared. Physical activity level was
      also low among school children. There must be serious systematic implementation
      of action plans to combat the high prevalence of diabetes and associated risk
      factors.

PMID- 28513625
TI  - Diagnostic criteria for diabetes in China: are we pushing too much beyond
      evidence?

PMID- 28513630
TI  - IBD: Tofacitinib effective in ulcerative colitis.

PMID- 28513627
TI  - Neuromorphic device architectures with global connectivity through electrolyte
      gating.
AB  - Information processing in the brain takes place in a network of neurons that are
      connected with each other by an immense number of synapses. At the same time,
      neurons are immersed in a common electrochemical environment, and global
      parameters such as concentrations of various hormones regulate the overall
      network function. This computational paradigm of global regulation, also known as
      homeoplasticity, has important implications in the overall behaviour of large
      neural ensembles and is barely addressed in neuromorphic device architectures.
      Here, we demonstrate the global control of an array of organic devices based on
      poly(3,4ethylenedioxythiophene):poly(styrene sulf) that are immersed in an
      electrolyte, a behaviour that resembles homeoplasticity phenomena of the neural
      environment. We use this effect to produce behaviour that is reminiscent of the
      coupling between local activity and global oscillations in the biological neural
      networks. We further show that the electrolyte establishes complex connections
      between individual devices, and leverage these connections to implement
      coincidence detection. These results demonstrate that electrolyte gating offers
      significant advantages for the realization of networks of neuromorphic devices of
      higher complexity and with minimal hardwired connectivity.

PMID- 28513626
TI  - Fabrication of cerebral aneurysm simulator with a desktop 3D printer.
AB  - Now, more and more patients are suffering cerebral aneurysm. However, long
      training time limits the rapid growth of cerebrovascular neurosurgeons. Here we
      developed a novel cerebral aneurysm simulator which can be better represented the
      dynamic bulging process of cerebral aneurysm The proposed simulator features the
      integration of a hollow elastic vascular model, a skull model and a brain model,
      which can be affordably fabricated at the clinic (Fab@Clinic), under $25.00 each
      with the help of a low-cost desktop 3D printer. Moreover, the clinical blood flow
      and pulsation pressure similar to the human can be well simulated, which can be
      used to train the neurosurgical residents how to clip aneurysms more effectively.

PMID- 28513628
TI  - An integrated model for detecting significant chromatin interactions from high
      resolution Hi-C data.
AB  - Here we present HiC-DC, a principled method to estimate the statistical
      significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC
      uses hurdle negative binomial regression account for systematic sources of
      variation in Hi-C read counts-for example, distance-dependent random polymer
      ligation and GC content and mappability bias-and model zero inflation and
      overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell
      line, HiC-DC detects significant interactions at the sub-topologically
      associating domain level, identifying potential structural and regulatory
      interactions supported by CTCF binding sites, DNase accessibility, and/or active
      histone marks. CTCF-associated interactions are most strongly enriched in the
      middle genomic distance range (~700 kb-1.5 Mb), while interactions involving
      actively marked DNase accessible elements are enriched both at short (<500 kb)
      and longer (>1.5 Mb) genomic distances. There is a striking enrichment of longer
      range interactions connecting replication-dependent histone genes on chromosome
      6, potentially representing the chromatin architecture at the histone locus body.

PMID- 28513631
TI  - Paediatrics: Are human milk oligosaccharides the magic bullet for necrotizing
      enterocolitis?

PMID- 28513629
TI  - Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth:
      the missing link.
AB  - Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be
      predominantly related to psychological factors, has a microorganic basis in a
      subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of
      the diarrhoea-predominant subtype (defined as new development of IBS following
      acute infectious diarrhoea), is one such condition known to occur in up to 10-30%
      individuals after acute gastroenteritis. However, following acute infectious
      gastroenteritis, patients can also develop post-infectious malabsorption syndrome
      (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously
      excluded tropical sprue by appropriate investigations, including small intestinal
      biopsy, the frequency of tropical sprue among patients with PI-IBS is not known.
      Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated
      with IBS in general, and in particular diarrhoea-predominant IBS, including PI
      IBS. SIBO is also known to be associated with tropical sprue. As both IBS,
      particularly the subset probably associated with SIBO, and tropical sprue improve
      with antibiotic treatment, we provide evidence and an explanatory model to
      support a link among these disorders.

PMID- 28513633
TI  - NAFLD: A gut microbiome signature for advanced fibrosis diagnosis in NAFLD.

PMID- 28513634
TI  - Mitochondria-targeted platinum(ii) complexes: dual inhibitory activities on tumor
      cell proliferation and migration/invasion via intracellular trafficking of beta
      catenin.
AB  - Mitochondria-targeted therapy is an alternative strategy for cancer therapy and
      may overcome the problems of metastasis and drug resistance that usually occur in
      conventional treatment. In this work, we demonstrate the mitochondria-targeted
      delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer
      cells. PIP-platin showed selective delivery and accumulation in the mitochondria
      and exhibited toxicity against a variety of tumor cell lines. The mitochondria
      were disrupted by PIP-platin, along with the generation of reactive oxygen
      species, depolarization of mitochondrial membrane potential, release of
      cytochrome c and necrosis. Interestingly, PIP-platin can promote cell adhesion
      within several hours and the cells became hard to dislodge from the culture
      plate. A wound healing assay, transwell migration/invasion assay and 3D spheroid
      migration assay all demonstrated that PIP-platin can inhibit cell
      migration/invasion. To illustrate the associated mechanisms, we investigated the
      intracellular trafficking of beta-catenin, a central protein in the regulation of
      cell adhesion, and gene transcription for cell proliferation. Upon treatment with
      PIP-platin, this protein can translocate onto the plasma membrane for increased
      cell adhesion. In addition, PIP-platin was demonstrated to efficiently inhibit
      Wnt signaling by blocking the translocation of beta-catenin into the nuclei,
      thereby preventing cell proliferation. We demonstrate that, accordingly, PIP
      platin has remarkable potential for intracellular delivery in mitochondria and
      has inhibitory effects on cancer cell proliferation and migration/invasion
      through beta-catenin, and may therefore be exploited as a dual-functional
      antitumor drug candidate in cancer treatment.

PMID- 28513635
TI  - The impact of dark chocolate intake on arterial elasticity in individuals with
      HIV/AIDS undergoing ART: a randomized, double-blind, crossover trial.
AB  - An increase in the frequency of cardiovascular diseases has been observed in the
      HIV/AIDS population. Studies involving healthy subjects or subjects with other
      diseases have shown benefits of chocolate supplementation on endothelial function
      and vasodilation. We evaluate the impact of chocolate consumption on arterial
      elasticity in people living with human immunodeficiency virus - PLHIV. A double
      blind, crossover trial including 110 PLHIV (19 to 59 years) on antiretroviral
      therapy - ART for at least 6 months and with a viral load of <500 copies per mL
      was conducted. All subjects were randomly assigned to 15-d dietary supplements
      containing dark chocolate or placebo with a 15-d washout period. Each participant
      received one of the two sequences: A (dark chocolate, placebo chocolate); B
      (placebo chocolate, dark chocolate). Arterial elasticity was measured using the
      HDI/PulseWaveTM CR-2000 CardioVascular Profiling System(r). Body composition,
      lipid profile, C-reactive protein, and thiobarbituric acid reactive substances
      were also assessed. Analysis of variance (ANOVA) for repeated measures using the
      Stata 11.0(r) program was used for cross-over analysis. Most subjects were men
      (59.0%) and Caucasian (46.1%) and the mean age was 44.6 +/- 7.1 years. The mean
      time since diagnosis of HIV infection was 13.7 +/- 5.3 years and the mean
      duration of ART was 12.9 +/- 4.2 years. Chocolate consumption resulted in
      significant alterations in the large artery elasticity index - LAEI (p = 0.049)
      and the mean concentration of HDL-c was higher after supplementation with dark
      chocolate (p = 0.045). This is the first study to evaluate the effect of
      chocolate on arterial elasticity in PLHIV. The results showed that dark chocolate
      consumption for 15 days improved the elastic properties of the LAEI in PLHIV.
      These findings, added to the noninvasive method used, may expand the knowledge of
      CVDs in this population.

PMID- 28513636
TI  - Modular synthesis of self-assembling Janus-dendrimers and facile preparation of
      drug-loaded dendrimersomes.
AB  - Materials and methods aimed at the next generation of nanoscale carriers for
      drugs and other therapeutics are currently in great demand. Yet, creating these
      precise molecular arrangements in a feasible and straightforward manner
      represents a remarkable challenge. Herein we report a modular synthetic route for
      amphiphilic Janus-dendrimers via a copper-catalyzed click reaction (CuAAC) and a
      facile procedure, using simple injection, to obtain highly uniform dendrimersomes
      with efficient loading of the model drug compound propranolol. The resulting
      assemblies were analyzed by dynamic light scattering and cryogenic transmission
      electron microscopy revealing the formation of unilamellar and multilamellar
      dendrimersomes. The formation of a bilayer structure was confirmed using cryo-TEM
      and confocal microscopy visualization of an encapsulated solvatochromic dye (Nile
      Red). The dendrimersomes reported here are tunable in size, stable over time and
      display robust thermal stability in aqueous media. Our results expand the scope
      of dendrimer-based supramolecular colloidal systems and offer the means for one
      step fabrication of drug-loaded dendrimersomes in the size range of 90-200 nm,
      ideal for biomedical applications.

PMID- 28513632
TI  - How to stomach an epigenetic insult: the gastric cancer epigenome.
AB  - Gastric cancer is a deadly malignancy afflicting close to a million people
      worldwide. Patient survival is poor and largely due to late diagnosis and
      suboptimal therapies. Disease heterogeneity is a substantial obstacle,
      underscoring the need for precision treatment strategies. Studies have identified
      different subgroups of gastric cancer displaying not just genetic, but also
      distinct epigenetic hallmarks. Accumulating evidence suggests that epigenetic
      abnormalities in gastric cancer are not mere bystander events, but rather promote
      carcinogenesis through active mechanisms. Epigenetic aberrations, induced by
      pathogens such as Helicobacter pylori, are an early component of gastric
      carcinogenesis, probably preceding genetic abnormalities. This Review summarizes
      our current understanding of the gastric cancer epigenome, highlighting key
      advances in recent years in both tumours and pre-malignant lesions, made possible
      through targeted and genome-wide technologies. We focus on studies related to DNA
      methylation and histone modifications, linking these findings to potential
      therapeutic opportunities. Lessons learned from the gastric cancer epigenome
      might also prove relevant for other gastrointestinal cancers.

PMID- 28513637
TI  - The synergy between atomically dispersed Pd and cerium oxide for enhanced
      catalytic properties.
AB  - We report a photochemical synthesis of Pd/CeO2 catalysts with atomically
      dispersed Pd. Compared to atomically dispersed Pd/CeO2 with a cubic CeO2 support
      (Pd/CeO2-CP), atomically dispersed Pd/CeO2 with a truncated octahedral CeO2
      support (Pd/CeO2-TOP) exhibited higher activity and selectivity, owing to the
      synergy between Pd atoms and the (111) surface of CeO2. When compared to Pd/CeO2
      with Pd clusters and nanoparticles via chemical reduction, Pd/CeO2-TOP showed
      excellent activity with an enhancement factor of 324 in CO oxidation, as well as
      an activity enhancement by a factor of 344 in selective oxidation of benzyl
      alcohol.

PMID- 28513638
TI  - Automatic assignment of metal-containing peptides in proteomic LC-MS and MS/MS
      data sets.
AB  - Transition metal-containing proteins and enzymes are critical for the maintenance
      of cellular function and metal-based (metallo)drugs are commonly used for the
      treatment of many diseases, such as cancer. Detection and characterisation of
      metallodrug targets is crucial for improving drug-design and therapeutic
      efficacy. Due to the unique isotopic ratios of many metal species, and the
      complexity of proteomic samples, standard MS data analysis of these species is
      unsuitable for accurate assignment. Herein a new method for differentiating metal
      containing species within complex LCMS data is presented based upon the Smart
      Numerical Annotation Procedure (SNAP). SNAP-LC accounts for the change in
      isotopic envelopes for analytes containing non-standard species, such as metals,
      and will accurately identify, record, and display the particular spectra within
      extended LCMS runs that contain target species, and produce accurate lists of
      matched peaks, greatly assisting the identification and assignment of modified
      species and tailored to the metals of interest. Analysis of metallated species
      obtained from tryptic digests of common blood proteins after reactions with three
      candidate metallodrugs is presented as proof-of-concept examples and demonstrates
      the effectiveness of SNAP-LC for the fast and accurate elucidation of metallodrug
      targets.

PMID- 28513639
TI  - Strong enhancement of electrical conductivity in two-dimensional micrometer-sized
      RuO2 nanosheets for flexible transparent electrodes.
AB  - The enhancement in electrical transport properties of exfoliated individual RuO2
      NSs was systemically investigated for their application in flexible electronics
      and optoelectronics. Decoration of Ag NPs on the surface of the RuO2 NSs provides
      donor electrons and dramatically increases the electrical conductivity of the
      monolayer RuO2 NSs by up to 3700%. The n-type doping behavior was confirmed via
      Hall measurement analysis of the doped RuO2 NSs. The layer number- and
      temperature-dependence of the conductivity were also investigated. Moreover,
      carrier concentration and mobility were obtained from Hall measurements,
      indicating that the undoped RuO2 NSs had ambipolar transport and semi-metallic
      characteristics. Moreover, the Ag-doped RuO2 NS multilayer films on polycarbonate
      substrates were demonstrated by the Langmuir-Blodgett assembly methods, showing
      one-third reduction in the sheet resistance and extraordinarily high bending
      stability that the change in the resistance was less than 1% over 50 000 cycles.

PMID- 28513644
TI  - Light induced cytotoxicity of nitrofurantoin toward murine melanoma.
AB  - The cytotoxicity of nitrofurantoin (NFT) in the dark and after light exposure
      (UVA irradiation, lambda = 385 nm) was evaluated in murine melanoma B16F10 cells.
      NFT induces both cell proliferation and inhibition of cell viability. The
      dominance of one or the other effect depends on the drug concentration,
      incubation time (tinc) and irradiation dose. The uptake of NFT in these cells, as
      well as its photocytotoxicity, reaches saturation after 24 hours of incubation.
      The mechanism of cell death in the dark is associated with the enzymatic release
      of nitric oxide (NO). The increase of NFT cytotoxicity under light irradiation is
      associated with the increase of NO concentration due to photorelease. NO
      photorelease by NFT in solution was confirmed by chemiluminescence, while NO
      formation in cells was confirmed by fluorescence microscopy using DAF-2DA, a
      specific indicator of NO in living cells. The NFT does not enter nuclei,
      distributing preferentially in the cell cytoplasm, as shown by fluorescence
      microscopy.

PMID- 28513645
TI  - Electrode potential dependent desolvation and resolvation of germanium(100) in
      contact with aqueous perchlorate electrolytes.
AB  - The electrode potential dependence of the hydration layer on an n-Ge(100) surface
      was studied by a combination of in situ and operando electrochemical attenuated
      total reflection infrared (ATR-IR) spectroscopy and real space density functional
      theory (DFT) calculations. Constant-potential DFT calculations were coupled to a
      modified generalised Poisson-Boltzmann ion distribution model and applied within
      an ab initio molecular dynamics (AIMD) scheme. As a result, potential-dependent
      vibrational spectra of surface species and surface water were obtained, both
      experimentally and by simulations. The experimental spectra show increasing
      absorbance from the Ge-H stretching modes at negative potentials, which is
      associated with an increased negative difference absorbance of water-related OH
      modes. When the termination transition of germanium from OH to H termination
      occurs, the surface switches from hydrophilic to hydrophobic. This transition is
      fully reversible. During the switching, the interface water molecules are
      displaced from the surface forming a "hydrophobic gap". The gap thickness was
      experimentally estimated by a continuum electrodynamic model to be ~2 A. The
      calculations showed a shift in the centre of mass of the interface water by ~0.9
      A due to the surface transformation. The resulting IR spectra of the interfacial
      water in contact with the hydrophobic Ge-H show an increased absorbance of free
      OH groups, and a decreased absorbance of strongly hydrogen bound water.
      Consequently, the surface transformation to a Ge-H terminated surface leads to a
      surface which is weakening the H-bond network of the interfacial water in
      contact.

PMID- 28513646
TI  - Biocompatibility and therapeutic evaluation of magnetic liposomes designed for
      self-controlled cancer hyperthermia and chemotherapy.
AB  - Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining
      importance as an effective therapeutic modality for cancer. However, control and
      maintenance of optimum hyperthermia are major challenges in clinical settings due
      to the overheating of tissues. To overcome this problem, we developed a novel
      magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension
      of La0.75Sr0.25MnO3 (LSMO) and iron oxide (Fe3O4) nanoparticles for self
      controlled hyperthermia and chemotherapy. However, the general apprehension about
      biocompatibility and safety of the newly developed formulation needs to be
      addressed. In this work, in vitro and in vivo biocompatibility and therapeutic
      evaluation studies of the novel magnetic liposomes are reported. Biocompatibility
      study of the magnetic liposomes formulation was carried out to evaluate the signs
      of preliminary systemic toxicity, if any, following intravenous administration of
      the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic
      liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse
      model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following
      intratumoral injection of single or double doses of the magnetic liposomes with
      or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at
      3 days interval) with drug loaded magnetic liposomes following single dose
      administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356
      +/- 550 mm3) whereas the double dose treatment reduced the tumour growth by 3.6
      fold (mean tumour volume 1045 +/- 440 mm3) compared to their corresponding
      control (mean tumour volume 3782 +/- 515 mm3). At the end of the tumour efficacy
      studies, the presence of MNPs was studied in the remnant tumour tissues and vital
      organs of the mice. No significant leaching or drainage of the magnetic liposomes
      during the study was observed from the tumour site to the other vital organs of
      the body, suggesting again the potential of the novel magnetic liposomes
      formulation for possibility of developing as an effective modality for treatment
      of drug resistant or physiologically vulnerable cancer.

PMID- 28513647
TI  - IF5 affects the final stage of the Cl-F exchange fluorination in the synthesis of
      pentafluoro-lambda6-sulfanyl-pyridines, pyrimidines and benzenes with electron
      withdrawing substituents.
AB  - A difficult chlorine-fluorine (Cl-F) exchange fluorination reaction in the final
      stage of the preparation of pentafluoro-lambda6-sulfanyl-(hetero)arenes having
      electron-withdrawing substituents has now been elucidated through the use of
      iodine pentafluoride. A major side-reaction of C-S bond cleavage was sufficiently
      inhibited by the potential interaction between F and I with a halogen bonding.

PMID- 28513649
TI  - Recent advances in the chemical transformations of functionalized
      alkylidenecyclopropanes (FACPs).
AB  - During the past several years, functionalized alkylidenecyclopropanes (FACPs)
      have attracted intensive attention in synthetic chemistry. Many interesting
      transformations of FACPs have been developed to synthesize a lot of structurally
      diverse and valuable polycyclic and heterocyclic compounds. This review will
      classify FACPs into aryl-FACPs, alkyl-FACPs and ring-FACPs for the first time,
      and recent interesting chemical transformations in these research fields will be
      included, respectively, from 2011. Moreover, we will pay more attention to the
      clarification of the reaction mechanism, in which the C-C bond cleavage of
      alkylidenecyclopropanes (ACPs) will be emphasized.

PMID- 28513648
TI  - Radical-carbene coupling reaction: Mn-catalyzed synthesis of indoles from
      aromatic amines and diazo compounds.
AB  - An unprecedented coupling reaction between aromatic amines and diazo compounds
      was well developed, which afforded a bridge connecting between radical chemistry
      and metal carbene chemistry. This Mn-catalyzed tandem reaction also provided a
      fundamentally different and practical approach to the indole skeleton under mild
      conditions.

PMID- 28513650
TI  - Photo-induced copper-catalyzed C-H chalcogenation of azoles at room temperature.
AB  - Inexpensive copper catalysts enabled direct C-H chalcogenations at ambient
      temperature by means of photo-induced catalysis. The expedient copper catalysis
      set the stage for C-S and C-Se bond formation from readily accessible non
      volatile elemental chalcogens. The photo-assisted copper catalysis manifold
      proved suitable for a wide range of substrates with good functional group
      tolerance and exhibited high catalytic efficacy even at a reaction temperature of
      25  degrees C.

PMID- 28513651
TI  - A tripeptide-based self-shrinking hydrogel for waste-water treatment: removal of
      toxic organic dyes and lead (Pb2+) ions.
AB  - A triphenylalanine-based superhydrogel shows automatic syneresis (self
      compressing properties) with time and this self-shrinking behavior has been
      successfully utilized to remove toxic lead ions and organic dyes from waste-water
      efficiently with the ability to re-use for a few times.

PMID- 28513652
TI  - An electrochemiluminescence assay for sensitive detection of methyltransferase
      activity in different cancer cells by hybridization chain reaction coupled with a
      G-quadruplex/hemin DNAzyme biosensing strategy.
AB  - In this work, a highly sensitive electrochemiluminescence (ECL) assay was
      fabricated for the detection of human DNA (cytosine-5)-methyltransferase1 (DNMT1)
      activity in cancer cells. The ECL assay coupled hybridization chain reaction with
      a G-quadruplex/hemin DNAzyme biosensing strategy. The ECL intensity changes
      (DeltaI) allowed detection of DNMT1 activity down to 0.09 U mL-1, and DeltaI was
      proportional to the logarithm of the activity of DNMT1 within the range of 1.0 to
      30.0 U mL-1 in buffer solution. It also showed high sensitivity to DNMT1 activity
      in A549 cells, with a detection limit of about 2 cells. This ECL assay provides a
      promising platform for profiling of the mutational cells of tumors and shows a
      great potential for application to DNA methylation-related clinical diagnostics.

PMID- 28513653
TI  - 3D and 2D supramolecular assemblies and thermotropic behaviour of a carbo
      benzenic mesogen.
AB  - Hexaalkoxy-di(phenylethynyl)-tetraphenyl-carbo-benzenes bearing six CnH2n+1
      aliphatic chains (n = 12, 18) have been synthesized and characterized, including
      by single crystal XRD analysis. For n = 12, a liquid crystal behaviour was
      observed in the range of 109-130  degrees C. DSC, POM and PXRD analyses evidenced
      a rectangular columnar mesophase at 115  degrees C. The determined 3D lattice
      constants are consistent with 2D STM images of the so-called "carbo-mesogen"
      deposited on an HOPG surface.

PMID- 28513654
TI  - Rhodium-catalyzed synthesis of 1,2-dihydropyridine by a tandem reaction of 4-(1
      acetoxyallyl)-1-sulfonyl-1,2,3-triazole.
AB  - A tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole including
      formation of alpha-imino rhodium carbene, 1,2-migration of an acetoxy group and
      six electron electrocyclic ring closure was reported. The migration of the OAc
      group with excellent chemoselectivity was the crucial process, leading to the
      formation of 1,2-dihydropyridine specifically in up to 90% yield. Several
      transformations of the dihydropyridine product were also achieved illustrating
      the potential of the protocol in organic synthesis. Based on the observation of
      the intermediate, a plausible mechanism was proposed.

PMID- 28513655
TI  - Boron difluoride hemicurcuminoid as an efficient far red to near-infrared
      emitter: toward OLEDs and laser dyes.
AB  - A hemicurcuminoid boron difluoride complex is used as an emitter in organic light
      emitting diodes, showing far red/near-infrared electroluminescence with an
      external quantum efficiency as high as 2.1%. This dye blended in CBP thin films
      shows amplified spontaneous emission with a threshold of 22 MUJ cm-2 at 750 nm,
      making this compound attractive for organic semiconductor lasers operating in the
      near-infrared region.

PMID- 28513657
TI  - Copper-catalyzed hydroallylation of allenes employing hydrosilanes and allyl
      chlorides.
AB  - The hydroallylation of allenes was developed by employing a hydrosilane and allyl
      chlorides in the presence of a copper catalyst. The reaction provided (E)-1,5
      dienes mainly in good to high yields.

PMID- 28513656
TI  - Restoring the biophysical properties of decellularized patches through
      recellularization.
AB  - Various extracellular matrix (ECM) scaffolds, isolated through decellularization,
      were suggested as ideal biomimetic materials for 'Functional tissue engineering'
      (FTE). The decellularization process comprises a compromise between damaging and
      preserving the ultrastructure and composition of ECM-previously shown to affect
      cell survival, proliferation, migration, organization, differentiation and
      maturation. Inversely, the effects of cells on the ECM constructs' biophysical
      properties, under physiological-like conditions, remain still largely unknown. We
      hypothesized that by re-cellularizing porcine cardiac ECM (pcECM, as a model
      scaffold) some of the original biophysical properties of the myocardial tissue
      can be restored, which are related to the scaffold's surface and the bulk
      modifications consequent to cellularization. We performed a systematic
      biophysical assessment of pcECM scaffolds seeded with human mesenchymal stem
      cells (MSCs), a common multipotent cell source in cardiac regenerative medicine.
      We report a new type of FTE study in which cell interactions with a composite
      scaffold were evaluated from the perspective of their contribution to the
      biophysical properties of the construct surface (FTIR, WETSEMTM) and bulk (DSC,
      TGA, and mechanical testing). The results obtained were compared with acellular
      pcECM and native ventricular tissue serving as negative and positive controls,
      respectively. MSC recellularization resulted in an inter-fiber plasticization
      effect, increased protein density, masking of acylated glycosaminoglycans (GAGs)
      and active pcECM remodelling which further stabilized the reseeded construct and
      increased its denaturation resistance. The systematic approach presented herein,
      therefore, identifies cells as "biological plasticizers" and yields important
      methodologies, understanding, and data serving both as a reference as well as
      possible 'design criteria' for future studies in FTE.

PMID- 28513658
TI  - Capillary zone electrophoresis-mass spectrometry with microliter-scale loading
      capacity, 140 min separation window and high peak capacity for bottom-up
      proteomics.
AB  - Better peptide separation is required for bottom-up proteomics for further
      improving the proteome coverage. The two-dimensional liquid chromatography (2D
      LC) systems only explore differences among peptides in their hydrophobicity
      (reversed-phase, RP) and charge (strong cation/anion exchange, SCX/SAX).
      Alternative separation techniques with different separation mechanisms are
      required to further improve the separation. Capillary zone electrophoresis (CZE)
      is an attractive alternative because it has high efficiency for separation of
      biomolecules and it separates analytes based on their size-to-charge ratios,
      complementary with LC. However, the low loading capacity and narrow separation
      window of CZE limit its wide application for large-scale proteomics. In this
      manuscript, we present an automated CZE-mass spectrometry (MS) system for solving
      those issues. The CZE-MS system can approach at least half-a-microliter loading
      capacity with good robustness and reproducibility, can routinely use over 12% of
      the available sample in the sample vial for analysis, and can generate a 140 min
      separation window and high peak capacity (~380) for complex proteome analysis.
      The results represent the highest peak capacity and the widest separation window
      of CZE for peptide separation with a microliter-scale loading capacity. It is the
      first time that CZE-MS approaches both the microliter-scale loading capacity and
      over 2-hour separation window for analysis of complex samples. The automated CZE
      MS system dramatically reduces the gap between CZE-MS and RPLC-MS in terms of
      loading capacity, separation window and peak capacity. It truly opens the door
      for large-scale bottom-up proteomics using CZE-MS.

PMID- 28513660
TI  - Access to dihydropyridinones and spirooxindoles: application of N-heterocyclic
      carbene-catalyzed [3+3] annulation of enals and oxindole-derived enals with 2
      aminoacrylates.
AB  - A strategy for the NHC-catalyzed synthesis of dihydropyridinones and
      spirooxindoles has been developed via [3+3] annulation reactions of enals or
      isatin-derived enals with 2-aminoacrylates under oxidative conditions. In this
      efficient strategy, the 2-aminoacrylates served as nucleophiles. Modifying the
      standard base switched the carbon-carbon double bond formation from 5,6-positions
      to 3,4-positions to generate 5,6-dihydropyridinones and 3,4-dihydropyridinones,
      respectively. Meanwhile, a diverse set of spirooxindole derivatives were also
      synthesized in good to excellent yields.

PMID- 28513659
TI  - Serum-resistant, reactive oxygen species (ROS)-potentiated gene delivery in
      cancer cells mediated by fluorinated, diselenide-crosslinked polyplexes.
AB  - The transfection performance of polycations is often hampered by various systemic
      barriers that pose conflicting requirements for material design. Herein, we
      developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and
      serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency
      between DNA condensation and release, and the inconsistency between cellular
      internalization and serum stability. Low-molecular weight (MW) PEI was cross
      linked with a diselenide-containing linker and further modified with fluorocarbon
      chains. The obtained high-MW DSe-PEI-F has potent DNA condensation as well as
      intracellular DNA delivery capabilities, while in the cytoplasm of cancer cells,
      it can rapidly degrade into low-MW segments upon ROS treatment to promote DNA
      release and reduce the material toxicity. As such, DSe-PEI-F showed high
      transfection efficiencies in cancer cells in the presence of serum, outperforming
      the commercial reagent PEI 25k by several orders of magnitude. This study thus
      provides an effective approach to overcome various barriers against non-viral
      gene delivery, which contributes to the development of a new class of gene
      vectors with high efficiency and low toxicity.

PMID- 28513661
TI  - A zwitterionic hydrocarbon-soluble borenium ion based on a beta-diketiminate
      backbone.
AB  - A versatile synthetic route has been developed to access strongly Lewis acidic
      borenium cations (and heavier group 13 analogues) featuring a pendant weakly
      coordinating borate function. The hydrocarbon-soluble borenium/borate zwitterion
      is more strongly Lewis acidic than B(C6F5)3, despite featuring a pendant (non
      fluorinated) aryl group and two flanking N-donors.

PMID- 28513662
TI  - Chemical synthesis of dual labeled proteins via differently protected alkynes
      enables intramolecular FRET analysis.
AB  - We report a novel method for multisite protein conjugation by setting differently
      silyl-protected alkynes as conjugation handles, which can remain intact through
      the whole synthetic procedure and provide sequential and orthogonal conjugation.
      This strategy enables efficient preparation of a dual dye-labeled protein and
      structural analysis via an intramolecular FRET mechanism.

PMID- 28513663
TI  - Reductive activation of O2 by a bioinspired Fe complex for catalytic epoxidation
      reactions.
AB  - Aerobic epoxidation of olefins catalyzed by iron complexes without the use of a
      sacrificial coreductant is unknown. We report the reductive activation of O2 by a
      bioinspired [(bTAML)FeIII(H2O)]- (1) complex to catalyze the epoxidation of
      alkenes with TONs of up to 80. Spectroscopic and kinetic evidence indicates the
      involvement of FeV(O) as the active oxidant during the reaction.

PMID- 28513664
TI  - A resilient and luminescent stimuli-responsive hydrogel from a heterotopic 1,8
      naphthalimide-derived ligand.
AB  - A heterotopic naphthalimide ligand N-(4-picolyl)-4-(4'-carboxyphenoxy)-1,8
      naphthalimide HL is utilised for the formation of self-assembled soft materials.
      In the presence of K+ ions, L- forms a robust photoluminescent hydrogel 1 which
      is reversible under thermal, mechanical or chemical stimuli.

PMID- 28513665
TI  - A fully integrated microchip system for automated forensic short tandem repeat
      analysis.
AB  - We have successfully developed an integrated microsystem that combines two
      plastic microchips for DNA extraction and PCR amplification with a glass
      capillary array electrophoresis chip together in a compact control and detection
      instrument for automated forensic short tandem repeat (STR) analysis. DNA
      extraction followed by an "in situ PCR" was conducted in a single reaction
      chamber of the microchip based on a filter paper-based extraction methodology.
      PCR products were then mixed with sizing standards by an injection electrode and
      injected into the electrophoresis chip for four-color confocal fluorescence
      detection. The entire STR analysis can be completed in about two hours without
      any human intervention. Since the 15-plex STR system has a more stringent
      requirement for PCR efficiency, we optimized the structure of the plastic DNA
      extraction and amplification chip, in which the reaction chamber was formed by
      sandwiching a hollow structure layer with two blank cover layers, to reduce the
      adsorption of PCR reagents to the surfaces. In addition, PCR additives, bovine
      serum albumin, poly(ethylene glycol), and more magnesium chloride were included
      into the on-chip multiplex STR system. The limit-of-detection study demonstrated
      that our microsystem was able to produce full 15-plex STR profiles from 3.75 ng
      standard K562 DNA. Buccal swab and whole blood samples were also successfully
      typed by our system, validating the feasibility of performing rapid DNA typing in
      a "sample-in-answer-out" manner for on-site forensic human identification.

PMID- 28513666
TI  - High performance solution-processable tetrathienoacene (TTAR) based small
      molecules for organic field effect transistors (OFETs).
AB  - Three new organic semiconductors with alkyl chain-substituted tetrathienoacene
      (TTAR) as the central core and both ends capped with thiophene (DT-TTAR),
      thienothiophene (DTT-TTAR) and dithienothiophene (DDTT-TTAR) have been
      synthesized and characterized for organic field effect transistor (OFET)
      applications. A hole mobility of 0.81 cm2 V-1 s-1 was achieved for the DDTT-TTAR
      film, which represents the highest mobility yet found for a solution-processable
      p-type TTAR-based small molecular semiconductors.

PMID- 28513667
TI  - Hierarchical self-supported ZnAlEu LDH nanotubes hosting luminescent CdTe quantum
      dots.
AB  - Self-supported oligo-layered ZnAlEu LDH nanotubes (? 20 nm) self-assemble upon
      controlled hydrolysis of the metal ions (Zn2+, Al3+, Eu3+) in the presence of
      1,3,5-benzenetricarboxylate anions and non-ionic worm-like micelles. Their high
      surface area and easily accessible cylindrical mesopores (175 m2 g-1; 0.75 cm3 g
      1) facilitate interaction with 5 nm CdTe quantum dots, enhancing the overall
      luminescence behavior.

PMID- 28513668
TI  - Computational analysis of site differences in selective aliphatic C-H
      hydroxylation by nonheme iron-oxo complexes.
AB  - Selective C-H hydroxylation by nonheme iron complexes offers a promising method
      in the field of organic synthesis. Aliphatic C-H bond oxidation reactions of
      pivalate (R) catalyzed by [Fe(S,S-PDP)(CH3CN)2]2+ (CAT1) were examined using the
      density functional theory. Our calculations of the CH3CN solvent agree with the
      experimental findings. However, it was observed that the gas-phase results did
      not replicate selective C-H hydroxylation observed experimentally when CAT1
      catalyzed hydrocarbon oxidations by H2O2via an HO-FeV[double bond, length as m
      dash]O oxidant (CAT1a). We inferred that the difference was mainly from hydrogen
      bonding formation, (CAT1a) O-HO[double bond, length as m-dash]C (R), in certain
      gaseous H-abstraction transition states (TSH). Then, the appearance of the
      stronger (CAT1a) O-HN[triple bond, length as m-dash]CCH3-solvent weakened the
      aforementioned interaction, leading to C-H activation influenced primarily by
      their electronic and steric properties. Such a deduction explained the same
      selective C-H found in both phases of reactions with CAT1b, a cyclic ferric
      peracetate oxidant, by the reason of TSH without the influence of H-bonding.
      Another interesting finding was that the commonly recognized radical intermediate
      was further isomerized by a favorable electron rearrangement. Thus, the
      subsequent OH-rebound behavior proceeded by an electrostatic interaction. This
      study provides mechanistic clues for modifying regioselective C-H hydroxylation
      for molecule synthesis applications.

PMID- 28513670
TI  - Effects of the asphaltene structure and the tetralin/heptane solvent ratio on the
      size and shape of asphaltene aggregates.
AB  - Asphaltene molecules, which consist of differently hydrogenated polyaromatic
      cores grafted with side alkyl chains of different sizes and grafting densities,
      were simulated with a solvent mixture of heptane and tetralin using coarse
      grained force fields. Starting with the initial configuration of randomly
      distributed asphaltene molecules and solvents, the asphaltene molecules aggregate
      because of the attractive force between their polyaromatic cores, but their sizes
      and shapes differ. The average aggregate size decreases with an increase in the
      hydrogenated polycyclic core, side-chain length, and tetralin concentration,
      which agree with experimental observations in the hydrocracking process. The
      number of side chains also influences the aggregate size but only in the presence
      of tetralin. In particular, the effect of tetralin addition occurs more
      significantly for asphaltene molecules with more side chains because side chains
      sterically block the intermolecular interactions between polyaromatic cores,
      which makes it easier for the aromatic ring of tetralin to bind to the
      polyaromatic core of asphaltene. These steric effects of side chains yield
      different shapes of aggregates, showing parallel stacking (face-to-face) for
      aromatic cores with many side chains, and T-shape (edge-to-face) or offset
      parallel stacking for those with fewer side chains. These findings agree with the
      experimental observation regarding the effect of tetralin on the solubility of
      asphaltene, and indicate that the extent of the tetralin effect depends on the
      number of side alkyl chains, implying that tetralin solvents need to be added
      with consideration for the structural change of asphaltene under hydrogenation or
      dealkylation conditions.

PMID- 28513669
TI  - The open-cubane oxo-oxyl coupling mechanism dominates photosynthetic oxygen
      evolution: a comprehensive DFT investigation on O-O bond formation in the S4
      state.
AB  - The dioxygen formation mechanism of biological water oxidation in nature has long
      been the focus of argument; many diverse mechanistic hypotheses have been
      proposed. Based on a recent breakthrough in the resolution of the electronic and
      structural properties of the oxygen-evolving complex in the S3 state, our density
      functional theory (DFT) calculations reveal that the open-cubane oxo-oxyl
      coupling mechanism, whose substrates preferably originate from W2 and O5 in the
      S2 state, emerges as the best candidate for O-O bond formation in the S4 state.
      This is justified by the overwhelming energetic superiority of this mechanism
      over alternative mechanisms in both the isomeric open and closed-cubane forms of
      the Mn4CaO5 cluster; spin-dependent reactivity rooted in variable magnetic
      couplings was found to play an essential role. Importantly, this oxygen evolution
      mechanism is supported by the recent discovery of femtosecond X-ray free electron
      lasers (XFEL), and the origin of the observed structural changes from the S1 to
      S3 state has been analyzed. In this view, we corroborate the proposed water
      binding mechanism during S2-S3 transition and correlate the theoretical models
      with experimental findings from aspects of substrate selectivity according to
      water exchange kinetics. This theoretical consequence for native metalloenzymes
      may serve as a significant guide for improving the design and synthesis of
      biomimetic materials in the field of photocatalytic water splitting.

PMID- 28513671
TI  - Temporal analysis of blister evolution during anion intercalation in graphite.
AB  - In the currently accepted picture, when graphite is immersed and polarized in a
      diluted sulfuric acid electrolyte, the surface undergoes an invasive process due
      to the intercalation of solvated sulphate anions inside the crystal. The
      following evolution of CO, CO2 and O2 promotes the surface swelling and the
      growth of blisters. Here, we give evidence that the appearance of blisters
      affects the graphite surface as soon as the oxygen potential is reached, i.e.
      before the traditionally accepted anion intercalation stage, which instead is
      demonstrated slowing the blister development. These results suggest a new picture
      of the solvated anion intercalation in graphite with respect to the current
      interpretative model.

PMID- 28513672
TI  - A computational study of the electronic properties, ionic conduction, and thermal
      expansion of Sm1-xAxCoO3 and Sm1-xAxCoO3-x/2 (A = Ba2+, Ca2+, Sr2+, and x = 0.25,
      0.5) as intermediate temperature SOFC cathodes.
AB  - The substitutional doping of Ca2+, Sr2+, and Ba2+ on the Sm-site in the cubic
      perovskite SmCoO3 is reported to improve both electronic and ionic conductivities
      for applications as solid oxide fuel cell (SOFC) cathodes. Hence, in this study
      we have used density functional theory (DFT) calculations to investigate dopant
      configurations at two different dopant concentrations: 25 and 50%. To preserve
      the electroneutrality of the system, we have studied two different charge
      compensation mechanisms: the creation of oxygen vacancies, and electronic holes.
      After examining the electronic structure, charge density difference, and oxygen
      vacancy formation energies, we concluded that oxygen vacancy charge compensation
      is the preferred mechanism to maintain the electroneutrality of the system.
      Furthermore, we found that the improvement of the electronic conduction is not a
      direct consequence of the appearance of electron holes, but a result of the
      distortion of the material, more specifically, the distortion of the Co-O bonds.
      Finally, molecular dynamics were employed to model ionic conduction and thermal
      expansion coefficients. It was found that all dopants at both concentrations
      showed high ionic conduction comparable to experimental results.

PMID- 28513673
TI  - Stability, electronic structure, and optical properties of protected gold-doped
      silver Ag29-xAux (x = 0-5) nanoclusters.
AB  - In this work, we used density functional theory (DFT) and linear response time
      dependent DFT (LR-TDDFT) to investigate the stability, electronic structure, and
      optical properties of Au-doped [Ag29-xAux(BDT)12(TPP)4]3- nanoclusters (BDT: 1,3
      benzenedithiol; TPP triphenylphosphine) with x = 0-5. The aim of this work is to
      shed light on the most favorable doped structures by comparing our results with
      previously published experimental data. The calculated relative energies, ranging
      between 0.8 and 10 meV per atom, indicate that several doped Ag29-xAux
      nanoclusters are likely to co-exist at room temperature. However, only the Au
      doped [Ag29-xAux(BDT)12(TPP)4]3- nanoclusters that have direct bonding between Au
      dopants and phosphines display an enhancement in the electronic transitions at
      ~450 nm. This agrees with the main spectral absorption features that have been
      experimentally reported for the mixture of Au-doped silver Ag29-xAux
      nanoclusters. In addition, the formation of the Au-TPP bond could prevent cluster
      degradation starting from the detachment of the phosphine molecules, since the Au
      TPP bond is stronger by ~0.4 eV than the analogous Ag-TPP one. Thus, the results
      presented here show the important role of Au-TPP bonding in determining the
      stability and optical properties of thiolate/phosphine-protected Ag29-xAux
      nanoclusters.

PMID- 28513674
TI  - Molecular organization in the twist-bend nematic phase by resonant X-ray
      scattering at the Se K-edge and by SAXS, WAXS and GIXRD.
AB  - Using a magnetically aligned liquid crystal mixture containing a novel Se
      labelled dimer and the difluoroterphenyl dimer DTC5C7, the twist-bend nematic
      phase (Ntb) was studied by the resonant scattering of hard X-rays and by
      conventional small and wide-angle X-ray scattering (SAXS, WAXS). Resonant
      diffraction spots indicated a helix with a 9-12 nm pitch in the Ntb phase and an
      unprecedentedly high helix orientation. This enabled deconvolution of global and
      local order parameters. These findings, combined with the simultaneously recorded
      resonant and non-resonant SAXS and WAXS data, allowed us to construct a locally
      layered molecular model of the Ntb phase, where the average twisted conformation
      of each molecule was idealised as a helical segment, matching the local
      heliconical director field. The dimers were found to be less bent in the Ntb
      phase than in their minimum energy conformation, and straightening further with
      increasing temperature. It is proposed that on further heating their low bend
      angle allows the transition to the normal nematic phase, where the molecules can
      freely move longitudinally, without the need to perform screw-like motion as in
      the Ntb phase. At the low-temperature end, the increasing molecular twist becomes
      unsustainable, leading to a transition to a smectic phase, where no twist is
      required.

PMID- 28513675
TI  - Photophysical properties and the NO photorelease mechanism of a ruthenium
      nitrosyl model complex investigated using the CASSCF-in-DFT embedding approach.
AB  - A complete state-averaged active space self-consistent field (SA-CASSCF)
      calculation by means of the SA-CASSCF(18,14)-in-BP86 Miller-Manby embedding
      approach was performed to explore the ground and excited electronic states of the
      trans-[RuCl(NO)(NH3)4]2+ complex. Insights into the NO photodissociation
      mechanism and Ru-NO bonding properties are provided. In addition, spin-orbit (SO)
      interactions were taken into account to describe and characterize the spin
      forbidden transitions observed at the low-energy regions of the trans
      [RuCl(NO)(NH3)4]2+ UV-Vis spectrum. The SA-CASSCF(18,14)-in-BP86 electronic
      spectrum is in great agreement with the experimental data of Schreiner [Schreiner
      et al., Inorg. Chem., 1972, 11, 880].

PMID- 28513676
TI  - Intermediate phases during solid to liquid transitions in long-chain n-alkanes.
AB  - The solid to liquid phase transition of n-alkanes with more than ten carbon atoms
      is an interesting phenomenon relevant to many fields, from cosmetics to
      automotive. Here we report Raman spectroscopy of tetradecane, pentadecane and
      hexadecane as a function of temperature. In order to gain information on the
      structural changes that the hydrocarbons undergo during melting, and to determine
      the temperature and the speed at which the phase change occurs, their temperature
      dependent Raman spectra are acquired. The spectra are analysed not only with
      respect to frequency shifts, band widths, and intensity ratio of certain bands,
      but also using a principal component analysis. The spectroscopic data suggest
      that the solid to liquid phase transition in hexadecane, differently from
      tetradecane and pentadecane, is almost instantaneous. Tetradecane shows a
      slightly faster transition than pentadecane. In addition, a rotator phase as an
      intermediate state between the liquid and crystalline solid phases is identified
      in pentadecane. Different characteristic features in the solid spectra of the
      hydrocarbons relate tetradecane and hexadecane to a tryclinic crystalline
      structure, and pentadecane to an orthorhombic structure.

PMID- 28513677
TI  - Regular and red-shifted fluorescence of the donor-acceptor compound 5-(1H-pyrrole
      1-yl)thiophenecarbonitrile (TCN) is efficiently quenched by internal modes of
      thiophene.
AB  - The photochemical properties of thiophene analogs of N-pyrrolobenzonitrile (PBN),
      notably the two isomers 5-(1H-pyrrole-1-yl)thiophene-2-carbonitrile (2-TCN) and 5
      (1H-pyrrole-1-yl)thiophene-3-carbonitrile (3-TCN) have been investigated. The aim
      of this study is to reveal whether the donor-acceptor compound TCN shows a
      fluorescence behavior similar to other benzonitrile derivatives like PBN and N,N
      dimethylaminobenzonitrile (DMABN). For this purpose high-level ab initio methods
      have been employed comprising approximate coupled cluster (CC2) methods, the
      algebraic-diagramatic construction scheme for the polarization propagator (ADC(2)
      and ADC(3)) as well as time-dependent density functional theory (TDDFT). Solvent
      effects have been included using continuum solvation models. In the gas phase
      excited TCN molecules most likely deactivate in a radiationless fashion to the
      ground state via a low lying S1/S0 conical intersection. In polar solvents the
      dark S(CT) (S2) state is stabilized below S(pipi*) (S1), however, despite this
      stabilization radiationless decay to the ground state remains the most likely
      deactivation pathway. Nevertheless, population of a twisted minimum of the S(CT)
      state becomes energetically feasible. Hence it is predicted that TCN does not
      show any fluorescence in the gas phase, and if at all only weak red-shifted
      emission from a twisted intramolecular charge transfer (TICT) minimum may be
      observable in polar solvents.

PMID- 28513678
TI  - Mechanochemically induced sulfur doping in ZnO via oxygen vacancy formation.
AB  - Surface defects of ZnO nanoparticles were induced via mechanical stressing using
      a Turbula shaker mixer and a planetary ball mill, and the possibilities for
      surface modification and functionalization of the ZnO nanoparticles were
      exemplified by sulfur doping of activated ZnO. Raman spectroscopy reveals that
      the formation of oxygen vacancies (VO) does not only occur under high stressing
      conditions in a planetary ball mill but even upon rather 'mild stressing' in the
      shaker mixer. The temporal evolution of the vacancy concentration in ZnO stressed
      under different conditions can be described by a model that accounts for stress
      number and vacancy diffusion with diffusion coefficients of VO of 3.7 * 10-21 m2
      s-1 and 2.4 * 10-20 m2 s-1 for stressing in the shaker and the planetary ball
      mill, respectively. The thickness of the VO layer was estimated to be about 1 nm.
      Thiourea was mixed with defective ZnO particles, and then heated at various
      temperatures for sulfur-doping. A linear relationship between the amount of
      induced VO and the level of sulfur doping was found. Remarkably, mechanical
      activation is indispensable in order to control the level of sulfur doping
      quantitatively. High-angle annular dark field scanning transmission electron
      microscopy (HAADF STEM) observations with energy dispersive X-ray spectroscopy
      (EDX) analysis clearly revealed that the doped sulfur atoms are concentrated at
      the particle surface. Thus, ZnO (core)/ZnS (shell) structures are obtained easily
      via mechanochemical activation and subsequent thermal treatment.

PMID- 28513679
TI  - A novel synthesis of an Fe3+/Fe2+ layered double hydroxide ('green rust') via
      controlled electron transfer with a conducting polymer.
AB  - This report examines the influence of a conducting polymer on the crystal growth
      of labile green rust (GR) through hybridization with polypyrrole. All hybrids
      used in this study were prepared via one-pot co-precipitation at neutral pH, with
      specific stoichiometric ratios among all chemical species. The role of the
      conducting polymer and the effective stoichiometric ratio were demonstrated to
      facilitate the crystal growth of GR.

PMID- 28513680
TI  - Molecular structures of various alkyldichlorosilanes in the solid state.
AB  - A series of organodichlorosilanes RR'SiCl2 (R,R' = (CH2)3; (CH2)4; (CH2)5; Me,Me;
      Me,H; Me,Cl) was studied by single-crystal X-ray diffraction analyses. At ambient
      temperature liquid chlorosilanes (melting points in the range of 180-220 K) were
      transferred into glass capillaries and crystallized in situ on a diffractometer.
      In the solid state structure these chlorosilanes are monomeric, even in the case
      of the sterically less demanding 1,1-dichlorosilacyclobutane (CH2)3SiCl2.
      Interestingly, regardless the steric demand of the alkyl substituents, the
      dialkyldichlorosilanes exhibit essentially the same Cl-Si-Cl angle (for
      (CH2)3SiCl2, (CH2)4SiCl2, (CH2)5SiCl2, Me2SiCl2: 106.08(3) degrees , 106.07(4)
      degrees /105.86(4) degrees , 106.91(2) degrees  and 105.59(6) degrees ,
      respectively). Replacement of one alkyl group by hydrogen has only a marginal
      influence on the Cl-Si-Cl angle (MeHSiCl2 106.31(3) degrees ), whereas in MeSiCl3
      slightly wider Cl-Si-Cl angles are found (ranging between 107.04(11) degrees  and
      107.86(11) degrees ), in accordance with VSEPR. Computational analyses, i.e.,
      potential energy surface scans of the Cl-Si-Cl angle variation, of (CH2)3SiCl2,
      Me2SiCl2, MeHSiCl2 and H2SiCl2 reveal essentially identical energy profiles for
      the Cl-Si-Cl deformation in these four dichlorosilanes with basically
      superimposed curves for (CH2)3SiCl2 and Me2SiCl2, whereas with increasing H
      substitution the energetic minimum is shifted to a slightly wider Cl-Si-Cl angle.
      In the crystal packing only MeHSiCl2 exhibits weak intermolecular SiCl van der
      Waals contacts, whereas the Si-Cl moieties of the other five chlorosilanes engage
      in intermolecular ClH and (for (CH2)3SiCl2, (CH2)4SiCl2 and MeSiCl3) ClCl
      contacts.

PMID- 28513681
TI  - Heteroleptic iron(iii) Schiff base spin crossover complexes: halogen
      substitution, solvent loss and crystallite size effects.
AB  - The influence of the halogen substituent on the qsal moiety of iron(iii)
      heteroleptic compounds with the formulae [Fe(qsal-X)(thsa)].nMeCN, where qsal-X-
      = X-substituted quinolylsalicylaldimine; thsa2- = thiosemicarbazone
      salicylaldiminate; X = F; n = 2.5, 1.2.5MeCN and X = Cl 2, Br 3 and I 4, n = 1
      (labelled 2.MeCN, 3.MeCN and 4.MeCN, respectively) has been systematically
      investigated. Magnetic studies on solid samples show incomplete spin crossover in
      1-3 which can be related to MeCN solvent loss. Complex 4.MeCN remains fully LS up
      to 360 K. Single crystals have been examined at variable temperatures for samples
      possessing different degrees of solvation. Intermolecular C-XH interactions are
      present for X = F, Cl and Br while a C-Ipi interaction is uniquely observed in
      4.MeCN. These preferential interactions result in different supramolecular
      packings of the various halogen substituted compounds. However, as the LS
      stability increases from F to I, the ligand field strength is then also suggested
      to increase from F to I. Consequently, in this family, the electronic structure
      resulting from halogen variation is believed to influence the magnetic properties
      more than crystal packing effects. Mossbauer spectra, at variable temperatures,
      confirm the presence of Fe(iii) and the magnetic properties in these compounds.
      The effect of different drying methods as well as the crystal/powder effect on
      the magnetic properties are discussed in the case of 2.MeCN.

PMID- 28513684
TI  - Ultrafast IR spectroscopy of photo-induced electron transfer in self-assembled
      donor-acceptor coordination cages.
AB  - Photo-induced processes in self-assembled coordination cages were studied by
      femtosecond infrared pump-probe spectroscopy. Densely packed, interpenetrated
      double cages were constructed from eight bis-monodentate redoxactive ligands
      bound to four Pd(ii) nodes. Two types of ligands consisting of electron rich
      phenothiazine (PTZ) or electron deficient anthraquinone (ANQ) chromophores were
      used to assemble either homo-octameric or mixed-ligand cages. Upon
      photoexcitation the homo-octameric acceptor cage undergoes intersystem crossing
      to a long-lived triplet state, similar to the free acceptor ligand. Excitation of
      the free donor ligand leads to a fluorescent state with intramolecular charge
      transfer character. This fluorescence is completely quenched in the homo
      octameric donor double cage due to a ligand-to-metal charge transfer followed by
      back electron transfer on a ps timescale. Only for the mixed-ligand cage
      irradiation produces a charge separated state with an oxidized PTZ radical cation
      and a reduced ANQ radical anion as proven by their vibrational fingerprints in
      the transient IR spectra. In dichloromethane the lifetime of this charge
      separated state extends from tens of ps to >1.5 ns which is attributed to the
      broad distribution of mixed-ligand cages with different stoichiometry and/or
      stereo configurations.

PMID- 28513683
TI  - A theoretical study of low-lying singlet and triplet excited states of
      quinazoline, quinoxaline and phthalazine: insight into triplet formation.
AB  - Quinazoline, quinoxaline and phthalazine are nitrogen containing heterocyclic
      aromatic molecules which belong to the class diazanaphthalenes. These isomers
      have low-lying npi* and naphthalene-like pipi* states that interact via spin
      orbit coupling. In this contribution, we study their structure and electronic
      states by means of a coupled-cluster method. The computed properties are compared
      to those of cinnoline which were obtained in our previous study [Etinski et al.,
      Phys. Chem. Chem. Phys., 2014, 16, 4740]. The excited state features of these
      isomers are dependent on the position of the nitrogen atoms. We find that
      quinazoline and quinoxaline exhibit similarities in the ordering and character of
      the excited states. In contrast, a marked difference in the electronic and
      geometric structures of the lowest excited triplet states of cinnoline and
      phthalazine is noticed, although both are orthodiazanaphthalenes. Our findings
      suggest that the S1 [radiolysis arrow - arrow with voltage kink] T1 channel is
      responsible for the rapid intersystem crossing in quinazoline and quinoxaline,
      whereas the S1 [radiolysis arrow - arrow with voltage kink] T2 pathway is active
      in phthalazine.

PMID- 28513687
TI  - Modeling DNA oxidation in water.
AB  - A novel set of hole-site energies and electronic coupling parameters to be used,
      in the framework of the simplest tight-binding approximation, for predicting DNA
      hole trapping efficiencies and rates of hole transport in oxidized DNA is
      proposed. The novel parameters, significantly different from those previously
      reported in the literature, have been inferred from reliable density functional
      calculations, including both the sugar-phosphate ionic backbone and the effects
      of the aqueous environment. It is shown that most of the experimental oxidation
      free energies of DNA tracts and of oligonucleotides available from photoelectron
      spectroscopy and voltammetric measurements are reproduced with great accuracy,
      without the need for introducing sequence dependent parameters.

PMID- 28513686
TI  - A tri-functional vanadium(iv) complex to detect cysteine oxidation.
AB  - The development of effective molecular probes to detect and image the levels of
      oxidative stress in cells remains a challenge. Herein we report the design,
      synthesis and preliminary biological evaluation of a novel optical probe to
      monitor oxidation of thiol groups in cysteine-based phosphatases (CBPs).
      Following orthogonal protecting approaches we synthesised a new vanadyl complex
      designed to bind to CBPs. This complex is functionalised with a well-known
      dimedone derivative (to covalently trap sulfenic acids, SOHs) and a coumarin
      based fluorophore for optical visualization. We show that this new probe
      efficiently binds to a range of phosphatases in vitro with nanomolar affinity.
      Moreover, preliminary flow cytometry and microscopy studies in live HCT116 cells
      show that this probe can successfully image cellular levels of sulfenic acids -
      one of the species resulting from protein oxidative damage.

PMID- 28513689
TI  - Proton conduction in a hydrogen-bonded complex of copper(ii)-bipyridine
      glycoluril nitrate.
AB  - Bipyridine glycoluril (BPG), a urea-fused bipyridine tecton, forms a square
      pyramidal secondary building unit with copper(ii) which further self-assembles to
      give a porous hydrogen-bonded complex. This complex displays a high proton
      conductivity of 4.45 * 10-3 S cm-1 at 90  degrees C and 95% relative humidity
      (RH). Chains consisting of coordinated water, solvent water and nitrate anions
      embedded in the complex are responsible for high proton conduction. The proton
      conduction pathway was corroborated by ab initio electronic structure
      calculations with molecular dynamics (MD) simulations using the Nudged Elastic
      Band (NEB) method. The theoretical activation energy estimated to be 0.18 eV is
      in close agreement with the experimental value of 0.15 eV which evidences a
      Grotthuss proton hopping mechanism. We thus demonstrate that the hydrogen-bonded
      complex encapsulating appropriate counter ions, coordinated water and solvent
      water molecules exhibts superprotonic conductivity.

PMID- 28513688
TI  - Solution-processed two-dimensional layered heterostructure thin-film with
      optimized thermoelectric performance.
AB  - Graphene-based two-dimensional (2D) heterostructures have ignited intensive
      interest in recent years because of their excellent physical performance.
      However, the most common method to prepare them uses chemical vapor deposition,
      which has the drawback of a complex process unsuitable for large-scale
      production. In this respect, reduced graphene oxide and transitional metal
      dichalcogenides (rGO-TMDs) composite thin-films were fabricated by a simple
      solution-processing method and their thermoelectric performance was investigated
      systematically. Addition of rGO nanosheets (NSs) efficiently improved the
      electrical conductivity of MoS2 and WS2 (MS2) NSs, due to the excellent electron
      transport performance of rGO. Furthermore, it should be noted that an optimized
      content of rGO can effectively avoid direct contact between TMDs NSs by forming a
      rGO-TMDs heterojunction, leading to significantly increased electrical
      conductivity and a slight variation in its Seebeck coefficient. Our work obtained
      high thermoelectric performance heterostructures by inducing two kinds of layered
      materials using a simple method that may potentially be applied to other 2D
      layered materials to construct heterostructures for energy conversion.

PMID- 28513690
TI  - Influence of the nature and environment of manganese in Mn-BEA zeolites on NO
      conversion in selective catalytic reduction with ammonia.
AB  - Manganese-containing BEA zeolites, MnxSiBEA (x = 1-4 wt%) and Mn(I.E.)AlBEA, were
      prepared by a two-step post-synthesis method and a conventional wet ion-exchange,
      respectively, and applied as catalysts in the selective catalytic reduction of NO
      with ammonia (NH3-SCR). The physicochemical analysis of zeolite properties by
      high-energy-resolution fluorescence-detected XANES (HERFD-XANES) and X-ray
      emission spectroscopy (XES) uncovered that the coordination, geometry and
      oxidation state of Mn species are strongly related to the preparation method.
      Additionally, the study of catalyst acidity by FTIR spectroscopy with CO and
      pyridine probe molecules provided important insight into the number and type of
      acidic centres present on the catalyst surface. The catalytic results revealed
      that NO conversion depended on the state and content of Mn. The zeolites obtained
      by the two-step post-synthesis method and with a low Mn content were very active
      in the medium temperature range (NO conversion ~100%) with simultaneous high
      selectivity to N2 due to the presence of isolated, framework Mn(iii) and Mn(ii)
      species. The N2O formation was especially high in the case of catalysts
      containing extra-framework polynuclear Mn species and negligible in the case of
      Mn(I.E.)AlBEA containing predominantly isolated, extra-framework Mn(ii) species.

PMID- 28513691
TI  - Conformational behavior and stacking interactions of contorted polycyclic
      aromatics.
AB  - We present a systematic computational analysis of the conformations and stacking
      interactions of a set of 18 saddle-shaped, contorted polycyclic aromatic
      compounds at the B97-D3M(BJ)/TZV(2d,2p)//B97-D/TZV(2d,2p) level of theory. These
      doubly-concave systems offer a means of tuning the strength of stacking
      interactions through variations in molecular curvature, and understanding the
      intermolecular non-covalent interactions exhibited by these systems will aid the
      design of contorted polycyclic systems with precisely defined packing in the
      solid state. Computations reveal wide variations in both the nature of the low
      lying conformations and the stacking affinities of these systems. In particular,
      the introduction of both thiophene rings around the periphery of these systems
      and the incorporation of B and N atoms into the coronene core can greatly enhance
      their tendency to form strongly stacked dimers. Overall, these data provide a
      reminder that curvature does not always lead to stronger stacking interactions.

PMID- 28513692
TI  - Odd-even effect in two dimensions induced by the bicomponent blends of isobutenyl
      compounds.
AB  - Scanning tunneling microscopy (STM) investigation was performed for the blends of
      isobutenyl compounds, in which the long alkyl chains were connected with ester or
      carbamoyl linkages. Each component by itself did not show the odd-even effect of
      alkyl chain length, whereas after blending them, the 2D structures drastically
      changed and modulated to exhibit odd-even effect. Star, lozenge, twist-like, and
      linear structures were found, dependent on the blend ratio and alkyl chain
      length. The blend ratio dependence of 2D structures was explained in terms of
      homogeneous and heterogeneous dimerization due to the interdigitation of alkyl
      chains.

PMID- 28513693
TI  - Synthesis, characterization and in vitro and in vivo anticancer activity of
      Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)].
AB  - This report describes the synthesis, characterization and biological activity of
      a series of platinum(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10
      phenanthroline)] (Pt56MeSS) with non-bioactive, lipophilic and bioactive axial
      ligands. In an attempt to explore the anticancer activity potential of the Pt(iv)
      derivatives, 2D and 3D cytotoxic screening and a preliminary in vivo study were
      performed. The average IC50 values of the platinum(iv) derivatives ranged from
      1.26 to 5.39 MUM, compared with 1.24 MUM for Pt56MeSS, suggesting that the axial
      ligands have a relatively minor effect on the potency of the compounds.
      Preliminary in vivo studies indicate that the platinum(iv) derivatives of
      Pt56MeSS are active in vivo and can reduce the tumor to a similar extent to
      cisplatin.

PMID- 28513694
TI  - Atomic scale observation of a defect-mediated first-order phase transition in
      VO2(A).
AB  - The study of first-order structural transformations has attracted extensive
      attention due to their significant scientific and industrial importance. However,
      it remains challenging to exactly determine the nucleation sites at the very
      beginning of the transformation. Here, we report the atomic scale real-time
      observation of a unique defect-mediated reversible phase transition between the
      low temperature phase (LTP) and the high temperature phase (HTP) of VO2(A). In
      situ Cs-corrected scanning transmission electron microscopy (STEM) images clearly
      indicate that both phase transitions (from the HTP to the LTP and from the LTP to
      the HTP) start at the defect sites in parent phases. Intriguingly, the structure
      of the defects within the LTP is demonstrated to be the HTP of VO2 (A), and the
      defect in the HTP of VO2(A) is determined to be the LTP structure of VO2(A).
      These findings are expected to broaden our current understanding of the first
      order phase transition and shed light on controlling materials' structure
      property phase transition by "engineering" defects in applications.

PMID- 28513695
TI  - Surface passivation and self-regulated shell growth in selective area-grown GaN
      (Al,Ga)N core-shell nanowires.
AB  - The large surface-to-volume ratio of GaN nanowires implicates sensitivity of the
      optical and electrical properties of the nanowires to their surroundings. The
      implementation of an (Al,Ga)N shell with a larger band gap around the GaN
      nanowire core is a promising geometry to seal the GaN surface. We investigate the
      luminescence and structural properties of selective area-grown GaN-(Al,Ga)N core
      shell nanowires grown on Si and diamond substrates. While the (Al,Ga)N shell
      allows a suppression of yellow defect luminescence from the GaN core, an overall
      intensity loss due to Si-related defects at the GaN/(Al,Ga)N interface has been
      observed in the case of Si substrates. Scanning transmission electron microscopy
      measurements indicate a superior crystal quality of the (Al,Ga)N shell along the
      nanowire side facets compared to the (Al,Ga)N cap at the top facet. A nucleation
      study of the (Al,Ga)N shell reveals a pronounced bowing of the nanowires along
      the c-direction after a short deposition time which disappears for longer growth
      times. This is assigned to an initially inhomogeneous shell nucleation. A
      detailed study of the proceeding shell growth allows the formulation of a strain
      driven self-regulating (Al,Ga)N shell nucleation model.

PMID- 28513696
TI  - External electric field driving the ultra-low thermal conductivity of silicene.
AB  - The manipulation of thermal transport is in increasing demand as heat transfer
      plays a critical role in a wide range of practical applications, such as
      efficient heat dissipation in nanoelectronics and heat conduction hindering in
      solid-state thermoelectrics. It is well established that the thermal transport in
      semiconductors and insulators (phonons) can be effectively modulated by structure
      engineering or materials processing. However, almost all the existing approaches
      involve altering the original atomic structure of materials, which would be
      hindered due to either irreversible structure change or limited tunability of
      thermal conductivity. Motivated by the inherent relationship between phonon
      behavior and interatomic electrostatic interaction, we comprehensively
      investigate the effect of external electric field, a widely used gating technique
      in modern electronics, on the lattice thermal conductivity (kappa). Taking two
      dimensional silicon (silicene) as a model, we demonstrate that by applying an
      electric field (Ez = 0.5 V A-1) the kappa of silicene can be reduced to a record
      low value of 0.091 W m-1 K-1, which is more than two orders of magnitude lower
      than that without an electric field (19.21 W m-1 K-1) and is even comparable to
      that of the best thermal insulation materials. Fundamental insights are gained
      from observing the electronic structures. With an electric field applied, due to
      the screened potential resulting from the redistributed charge density, the
      interactions between silicon atoms are renormalized, leading to phonon
      renormalization and the modulation of phonon anharmonicity through electron
      phonon coupling. Our study paves the way for robustly tuning phonon transport in
      materials without altering the atomic structure, and would have significant
      impact on emerging applications, such as thermal management, nanoelectronics and
      thermoelectrics.

PMID- 28513697
TI  - Self-assembled nanohelix from a bolaamphiphilic diacetylene via hydrogelation and
      selective responsiveness towards amino acids and nucleobases.
AB  - A bolaamphiphile with diacteylene mesogen unit and l-glutamic acid as the
      terminal group was newly designed and its self-assembly was investigated. The
      compound formed hydrogels with water upon heating and cooling. The as-formed gel
      could be switched to a dispersion upon mechanical shaking. Both the gel and the
      water dispersion undergo polymerization upon UV irradiation. However, the gel
      turned to blue and then purple red color, while the dispersion turned red
      directly. Using AFM and SEM observations, it was found that nanohelix was formed
      in the as-prepared gel and polymerized blue gels, while nanobelt was formed from
      the water dispersion. The blue nanohelix was stable but showed selective response
      to certain amino acids and nucleobases. It was found that the blue gel underwent
      shrinkage when reacting with charged amino acids such as Glu, Asp, Lys, Arg and
      His. In the shrunk gel, the solution phase further turned pink in the case of His
      and Arg. In addition, the blue gel showed also shrinkage and color change when
      reacting with cytosine.

PMID- 28513698
TI  - Unzipping and shearing DNA with electrophoresed nanoparticles in hydrogels.
AB  - We show electric control of unzipping and shearing dehybridization of a DNA
      duplex anchored to a hydrogel. Tensile force is applied by electrophoresing (25 V
      cm-1) gold nanoparticles pulling the DNA duplex. The pulled DNA strand is
      gradually released from the hydrogel. The unzipping release rate is faster than
      shearing; for example, 3-fold for a 15 base pair duplex, which helps to design
      electrically driven DNA devices.

PMID- 28513700
TI  - Outstanding reviewers for Lab on a Chip in 2016.

PMID- 28513699
TI  - Multifunctional nanoprobes for both fluorescence and 19F magnetic resonance
      imaging.
AB  - Fluorescence is widely used for cell imaging due to its high sensitivity and rich
      color choice but limited for in vivo imaging because of its low light
      penetration. Meanwhile, magnetic resonance imaging (MRI) is widely applied for in
      vivo diagnosis but not suitable for cell imaging because of its low resolution.
      Compared to 1H-MRI, 19F-MRI is more suitable for clinical application due to its
      high sensitivity but fabricating 19F-MRI probes is a great challenge. Therefore,
      it is highly desirable to develop a dual-modal imaging probe for both cell
      fluorescence imaging and in vivo19F-MRI with high sensitivity and deep
      penetration. In this study, 19F moiety loaded nanocomposites with an organic
      fluorescent core were successfully prepared via a facile strategy by
      encapsulating organic dyes with oleylamine-functionalized polysuccinimide and
      1H,1H,2H,2H-perfluorodecyltriethoxysilane (PDTES). The aggregation of organic
      fluorescent dyes in the core results in significant fluorescence for optical
      imaging, while the 19F moieties on PDTES allow for simultaneous 19F MRI.
      Moreover, the nanocomposites exhibited high water dispersibility and excellent
      biocompatibility. These properties make them promising for both cell imaging and
      in vivo imaging applications.

PMID- 28513702
TI  - Stretchable impedance sensor for mammalian cell proliferation measurements.
AB  - This paper presents the fabrication and testing of a novel stretchable electric
      cell-substrate impedance sensing (ECIS) lab on a chip device. This is the first
      time that ECIS electrodes were fabricated on a stretchable polydimethylsiloxane
      (PDMS) substrate and ECIS measurements were performed on mammalian cells exposed
      to cyclic strain. The stretchable ECIS biosensors simulate in vitro the dynamic
      environment of organisms, such as pulsation, bending and stretching, which
      enables investigations on cell behavior that undergoes mechanical stimuli in
      biological tissue. Usually cell-based assays used in cell mechanobiology rely on
      endpoint cell tests, which provide a limited view on dynamic cellular mechanisms.
      The ECIS technique is a label-free, real-time and noninvasive method to monitor
      the cellular response to mechanical stimuli. Bovine aortic endothelial cells
      (BAECs) have been used in this research because the BAECs are exposed in vivo to
      cyclic physiologic elongation produced by blood circulation in the arteries.
      These innovative stretchable ECIS biosensors were used to analyze the
      proliferation of BAECs under different cyclic mechanical stimulations. The
      results of fluorescence based cell proliferation assays confirmed that the
      stretchable ECIS sensors were able to analyze in real-time the BAEC
      proliferation. The novel stretchable ECIS sensor has the ability to analyse cell
      proliferation, determine the cell number and density, and apply mechanical
      stimulation at the same time.

PMID- 28513703
TI  - Nonlinear photoluminescence in monolayer WS2: parabolic emission and excitation
      fluence-dependent recombination dynamics.
AB  - Recombination dynamics during photoluminescence (PL) in two-dimensional (2D)
      semiconducting transition metal dichalcogenides (TMDs) are complicated and can be
      easily affected by the surroundings because of their atomically thin structures.
      Herein, we studied the excitation power and temperature dependence of the
      recombination dynamics on the chemical vapor deposition-grown monolayer WS2via a
      combination of Raman, PL, and time-resolved PL spectroscopies. We found a red
      shift and parabolic intensity increase in the PL emission of the monolayer WS2
      with the increasing excitation power and the decay time constants corresponding
      to the recombination of trions and excitons from transient PL dynamics. We
      attributed the abovementioned nonlinear changes in the PL peak positions and
      intensities to the combination of increasing carrier interaction and band
      structure renormalization rather than to the thermal effect from a laser.
      Furthermore, the excitation power-dependent Raman measurements support our
      conclusion. These findings and understanding will provide important information
      for the development of TMD-based optoelectronics and photonics.

PMID- 28513704
TI  - Modeling the formation of TiO2 ultra-small nanoparticles.
AB  - The structures of TiO2 ultra-small nanoparticles (USNPs) at the atomistic level
      have been predicted because of their potential importance in catalytic,
      environmental, biological and energy applications. Low energy (TiO2)n clusters
      and USNPs (n up to 80 at the B3LYP/DZVP2 level, and up to 384 at the PM6 level)
      were found using a novel bottom-up global optimization approach that is based on
      all-atom real-space calculations. These structures include USNPs that belong to 1
      D, 2-D and 3-D USNP series where all the members share the same fragment types
      and local translational symmetries. Most of the metastable 2-D and 3-D USNPs
      contain tubular building blocks similar to the 1-D USNPs. The 3-D USNPs that
      resemble the bulk anatase are predicted to be energetically favorable structures
      for 64 <= n <= 384. A fragment-based model was developed to relate the energy
      with geometry for the 1-D, 2-D and 3-D USNPs. Surface energy densities were
      predicted for surface fragments at the different positions of the USNPs using
      this new model. Based on the predicted surface energy densities and the partial
      density of states, the most catalytically active sites for the anatase-like 3-D
      USNPs were predicted to be the kink sites on Face-x surfaces consisting of an
      octahedral-Ti, the step (edge) sites between the Face-x and Face-y surfaces
      consisting of a square pyramidal-Ti (on Face-x), and the step sites consisting of
      a trigonal bipyramidal Ti on the Face-y surfaces.

PMID- 28513705
TI  - On-demand curing of polydimethylsiloxane (PDMS) using the photothermal effect of
      gold nanoparticles.
AB  - The photothermal effect of gold nanoparticles (AuNPs) produces extremely
      localized heat that can be harnessed to drive large scale chemical reactions by
      simultaneously generating many individual reactions on the nanoscale. We use the
      photothermal effect to enhance the curing rate of polydimethylsiloxane (PDMS) by
      a factor of 4.9 * 109. Photothermal curing occurs via crosslinking reactions
      between vinyl and Si-H groups of the pre-polymer, and the course of the reaction
      was followed by monitoring the disappearance of infrared bands associated with
      these functional groups. Using mass spectroscopy, we verify that the major
      polymer m/z peaks are identical for both traditionally and photothermally cured
      polymers, indicating that the photothermal effect of AuNPs is an effective way in
      which to supply on-demand curing of PDMS.

PMID- 28513706
TI  - Control over the magnetism and transition between high- and low-spin states of an
      adatom on trilayer graphene.
AB  - Using density-functional theory, we investigate the electronic and magnetic
      properties of an adatom (Na, Cu and Fe) on ABA- and ABC-stacked (Bernal and
      rhombohedral) trilayer graphenes. In particular, we study the influence of an
      applied gate voltage on magnetism, as it modifies the electronic states of the
      trilayer graphene (TLG) as well as changes the adatom spin states. Our study
      performed for a choice of three different adatoms (Na, Cu, and Fe) shows that the
      nature of adatom-graphene bonding evolves from ionic to covalent in moving from
      an alkali metal (Na) to a transition metal (Cu or Fe). Applying an external
      electric field (EEF) to TLG systems with different stacking orders results in the
      transition between high- and low-spin states in the latter case (Cu, Fe) and
      induces a little of magnetism in the former (Na) without magnetism in the absence
      of an external electric field. Our study would be useful for controlled adatom
      magnetism and (organic) spintronic applications in nanotechnology.

PMID- 28513707
TI  - Systematic study of interdependent relationship on gold nanorod synthesis
      assisted by electron microscopy image analysis.
AB  - Here, we systematically investigated the independent, multiple, and synergic
      effects of three major components, namely, ascorbic acid (AA), seed, and silver
      ions (Ag+), on the characteristics of gold nanorods (GNRs), i.e., longitudinal
      localized surface plasmon resonance (LSPR) peak position, shape, size, and
      monodispersity. To quantitatively assess the shape and dimensions of GNRs, we
      used an automated transmission electron microscopy image analysis method using a
      MATLAB-based code developed in-house and the concept of solidity, which is the
      ratio between the area of a GNR and the area of its convex hull. The solidity of
      a straight GNR is close to 1, while it decreases for both dumbbell- and dogbone
      shaped GNRs. We found that the LSPR peak position, shape, and monodispersity of
      the GNRs all altered simultaneously with changes in the amounts of individual
      components. For example, as the amount of AA increased, both the LSPR peak and
      solidity decreased, while the polydispersity increased. In contrast, as the
      amount of seeds increased, both the LSPR and solidity increased, while the
      monodispersity improved. More importantly, we found that the influence of each
      component can actually change depending on the composition of the GNR growth
      solution. For instance, the LSPR peak position red-shifted as the amount of AA
      increased when the seed content was low, whereas it blue-shifted when the seed
      content was high.

PMID- 28513708
TI  - Symmetry-breaking charge transfer in the excited state of directly linked push
      pull porphyrin arrays.
AB  - Herein, we revealed a symmetry-breaking charge transfer (SBCT) process in the
      excited state of a directly linked push-pull porphyrin dyad (AD) and triad (ADA)
      via spectroscopic measurements including steady-state absorption and
      fluorescence, time-resolved fluorescence (TRF), femtosecond transient absorption
      (fs-TA), and time-resolved infrared (TRIR) measurements. Unprecedented broad
      fluorescence spectra were observed for porphyrin arrays in polar solvents; these
      were attributed to the existence of a charge transfer state as evidenced by the
      TRF measurements. TA measurements also revealed emerging features of a CT state
      for AD and ADA in polar solvents. These dynamics were also confirmed via TRIR
      measurements, which provided further information on the solvation and structural
      relaxation processes of the SBCT process. This is the first observation of an
      SBCT process in porphyrin arrays, providing fundamental understanding of the
      strongly coupled porphyrin arrays. Thus, the results of this study reveal the
      potential of the porphyrin arrays in relevant applications requiring SBCT.

PMID- 28513709
TI  - Correction: Optofluidic time-stretch imaging - an emerging tool for high
      throughput imaging flow cytometry.
AB  - Correction for 'Optofluidic time-stretch imaging - an emerging tool for high
      throughput imaging flow cytometry' by Andy K. S. Lau et al., Lab Chip, 2016, 16,
      1743-1756.

PMID- 28513710
TI  - Are highly morphed peptide frameworks lurking silently in microbial genomes
      valuable as next generation antibiotic scaffolds?
AB  - Antibiotics are a therapeutic class that, once deployed, select for resistant
      bacterial pathogens and so shorten their useful life cycles. As a consequence new
      versions of antibiotics are constantly needed. Among the antibiotic natural
      products, morphed peptide scaffolds, converting conformationally mobile, short
      lived linear peptides into compact, rigidified small molecule frameworks, act on
      a wide range of bacterial targets. Advances in bacterial genome mining,
      biosynthetic gene cluster prediction and expression, and mass spectroscopic
      structure analysis suggests many more peptides, modified both in side chains and
      peptide backbones, await discovery. Such molecules may turn up new bacterial
      targets and be starting points for combinatorial or semisynthetic manipulations
      to optimize activity and pharmacology parameters.

PMID- 28513711
TI  - A novel approach for fabricating highly tunable and fluffy bioinspired 3D
      poly(vinyl alcohol) (PVA) fiber scaffolds.
AB  - The excellent biocompatibility, biodegradability and chemo-thermal stability of
      poly(vinyl alcohol) (PVA) have been harnessed in diverse practical applications.
      These properties have motivated the fabrication of high performance PVA based
      nanofibers with adequate control over the micro and nano-architectures and
      surface chemical interactions. However, the high water solubility and
      hydrophilicity of the PVA polymer limits the application of the electrospun PVA
      nanofibers in aqueous environments owing to instantaneous dissolution. In this
      work, we report a novel yet facile concept for fabricating extremely light,
      fluffy, insoluble and stable three dimensional (3D) PVA fibrous scaffolds
      with/without coating for multifunctional purposes. While the solubility,
      morphology, fiber density and mechanical properties of nanofibers could be tuned
      by optimizing the cross-linking conditions, the surface chemical reactivity could
      be readily enhanced by coating with a polydopamine (pDA) bioinspired polymer
      without compromising the stability and innate properties of the native PVA fiber.
      The 3D pDA-PVA scaffolds exhibited super dye adsorption and constructive
      synergistic cell-material interactions by promoting healthy adhesion and
      viability of the human mesenchymal stem cells (hMSCs) within 3D micro-niches. We
      foresee the application of tunable PVA 3D as a highly adsorbent material and a
      scaffold material for tissue regeneration and drug delivery with close
      consideration of realistic in vivo parameters.

PMID- 28513712
TI  - Charge transport in C60-based single-molecule junctions with graphene electrodes.
AB  - We investigate charge transport in C60-based single-molecule junctions with
      graphene electrodes employing a combination of density functional theory (DFT)
      electronic structure calculations and Landauer transport theory. In particular,
      the dependence of the transport properties on the conformation of the molecular
      bridge and the type of termination of the graphene electrodes is investigated.
      Furthermore, electron pathways through the junctions are analyzed using the
      theory of local currents. The results reveal, in agreement with previous
      experiments, a pronounced dependence of the transport properties on the bias
      polarity, which is rationalized in terms of the electronic structure of the
      molecule. It is also shown that the edge states of zigzag-terminated graphene
      induce additional transport channels, which dominate transport at low voltages.
      The importance of the edge states for transport depends profoundly on the
      interface geometry of the junctions.

PMID- 28513713
TI  - One-step hydrothermal synthesis of photoluminescent carbon nanodots with
      selective antibacterial activity against Porphyromonas gingivalis.
AB  - Carbon dots (CDs) with high quantum yield (QY), low toxicity and good
      biocompatibility are the major quests of biomedical research. In this paper, we
      develop a green, simple hydrothermal approach to synthesize water-soluble,
      nontoxic, highly photoluminescent carbon nanodots (CNDs) from Metronidazole,
      which possess selective antibacterial activity against obligate anaerobes for the
      first time. Metronidazole was used as a sole precursor to prepare CNDs at 250 
      degrees C (CNDs-250) for 8 h. After the CNDs-250 with an average size of 2.9 nm,
      consisting of a highly carbon crystalline core and various surface groups were
      obtained, the formation and fluorescence mechanisms of CNDs were further explored
      by adjusting the reaction time and reaction temperatures, respectively.
      Biological experimental data proved that CNDs-250 can only inhibit the growth of
      obligate anaerobes, such as Porphyromonas gingivalis (P. gingivalis) directly,
      instead of further functionalization. Besides, CNDs-250 with a QY around 28.1%
      exhibit an obvious excitation-dependent emission, which will be conducive to
      multicolor bioimaging. And it may not only develop a new approach for researchers
      to prepare multifunctional CDs, but also provide a valuable strategy for the
      theranostics of some diseases as well as other fields.

PMID- 28513714
TI  - Highly water-stable rare ternary Ag-Au-Se nanocomposites as long blood
      circulation time X-ray computed tomography contrast agents.
AB  - X-ray computed tomography (CT) is a powerful and widely used medical non-invasive
      technique that often requires intravenous administration of contrast agents (CAs)
      to better visualize soft tissues. In this work, we have developed a novel CT
      contrast agent based on ternary Ag-Au-Se chalcogenide nanoparticles (NP). A
      facile ligand exchange by using a 3 kDa PEGylated ligand with a dithiol
      dihydrolipoic acid as an anchor group resulted in highly water-soluble and
      monodisperse nanoparticles. These PEGylated ternary NPs were tested in vivo in
      mice, showing slow uptake by the mononuclear phagocyte system, long blood
      circulation times, low toxicity, and very good X-ray contrast, thus being
      promising candidates as CT contrast agents for clinical applications.

PMID- 28513715
TI  - Heterogeneous Cu-Pd binary interface boosts stability and mass activity of atomic
      Pt clusters in the oxygen reduction reaction.
AB  - A ternary metallic CuPdPt nanocatalyst (NC) is synthesized using a wet chemical
      reduction method, which is sequentially designed, in the presence of acid treated
      carbon nanotubes. This NC is a nanocrystal with a configuration of a Cu@Pd core
      and atomic Pt clusters (~9 wt%) on the top (Cu@Pd/Pt). A residual current of
      92.6%, 5.2 times higher than that of commercial Pt catalysts (at 0.85 V vs. RHE),
      is retained after 40 000 cycles of an accelerated degradation test (ADT). Atomic
      and electronic structure analyses show that such exclusive stability mainly
      results from electron localization at Pt clusters in heterogeneous interfaces of
      the Cu-Pd core. Most importantly, we develop a robust ternary NC, which shows
      outstanding MA, superior chemical durability, and ~90 wt% lower Pt loading than
      commercial Pt NCs in the oxygen reduction reaction.

PMID- 28513716
TI  - Combining light-harvesting with detachability in high-efficiency thin-film
      silicon solar cells.
AB  - Efforts to realize thin-film solar cells on unconventional substrates face
      several obstacles in achieving good energy-conversion efficiency and integrating
      light-management into the solar cell design. In this report a technique to
      circumvent these obstacles is presented: transferability and an efficient light
      harvesting scheme are combined for thin-film silicon solar cells by the
      incorporation of a NaCl layer. Amorphous silicon solar cells in p-i-n
      configuration are fabricated on reusable glass substrates coated with an
      interlayer of NaCl. Subsequently, the solar cells are detached from the substrate
      by dissolution of the sacrificial NaCl layer in water and then transferred onto a
      plastic sheet, with a resultant post-transfer efficiency of 9%. The light
      trapping effect of the surface nanotextures originating from the NaCl layer on
      the overlying solar cell is studied theoretically and experimentally. The
      enhanced light absorption in the solar cells on NaCl-coated substrates leads to
      significant improvement in the photocurrent and energy-conversion efficiency in
      solar cells with both 350 and 100 nm thick absorber layers, compared to flat
      substrate solar cells. Efficient transferable thin-film solar cells hold a vast
      potential for widespread deployment of off-grid photovoltaics and cost reduction.

PMID- 28513717
TI  - In situ generation of less accessible Boc-imines from aldehydes: construction of
      a quaternary carbon by the Mannich reaction or unprecedented aldol reaction.
AB  - In situ generation of less accessible N-Boc-protected imines from aldehydes and
      their application to the direct three-component Mannich reaction with beta
      dicarbonyls were realized. The catalyst-free aldol reaction of ynals with beta
      dicarbonyls was also developed.

PMID- 28513720
TI  - Refinement of labile hydrogen positions based on DFT calculations of 1H NMR
      chemical shifts: comparison with X-ray and neutron diffraction methods.
AB  - Numerous gas phase electron diffraction, ultra-fast electron diffraction, X-ray
      and neutron diffraction experiments on beta-dicarbonyl compounds exhibiting enol
      enol tautomeric equilibrium, with emphasis on acetylacetone and dibenzoylmethane,
      have so far been reported with conflicting results on the structural details of
      the O-HO intramolecular hydrogen bond and resulted in alternative hypotheses on
      the intramolecular hydrogen bond potential function either a double minimum
      potential corresponding to two tautomeric forms in equilibrium or a single
      symmetrical one. We demonstrate herein, firstly, that the DFT calculated OH 1H
      NMR chemical shifts of acetylacetone and dibenzoylmethane exhibit a strong linear
      dependence on the computed OO hydrogen bond length of ~-50 ppm A-1 and as a
      function of the O-HO bond angle of ~1 ppm per degree, upon the transfer of the
      hydrogen atom from the ground state toward the transition state. Secondly, the
      refinement of labile hydrogen atomic positions in intramolecular hydrogen bonds
      based on the root-mean-square deviation between experimentally determined and DFT
      calculated 1H NMR chemical shifts in solution can provide high resolution
      structures of O-H and O(H)O bond lengths and O-HO bond angles with an accuracy of
      ~10-2 A and ~0.5 degrees , respectively. Thirdly, the calculated 1H NMR chemical
      shifts in solution of the two ground state tautomers in equilibrium of
      acetylacetone and dibenzoylmethane are in excellent agreement with the
      experimental value, even for moderate basis sets for energy minimization. In
      contrast, the single symmetrical structure in a strongly delocalized system is a
      transition state with calculated 1H NMR chemical shifts which strongly deviate
      from the experimental value. Fourth, the DFT calculated ground state O-H bond
      lengths of acetylacetone and dibenzoylmethane are in quantitative agreement with
      the literature data which take into account the effect of quantum nuclear motion.
      The DFT structural results are critically discussed with respect to the state-of
      the-art variable temperature X-ray and neutron diffraction methods.

PMID- 28513721
TI  - Programmable micrometer-sized motor array based on live cells.
AB  - Trapping and transporting microorganisms with intrinsic motility are important
      tasks for biological, physical, and biomedical applications. However, fast
      swimming speed makes the manipulation of these organisms an inherently
      challenging task. In this study, we demonstrated that an optoelectrical
      technique, namely, optically induced dielectrophoresis (ODEP), could effectively
      trap and manipulate Chlamydomonas reinhardtii (C. reinhardtii) cells swimming at
      velocities faster than 100 MUm s-1. Furthermore, live C. reinhardtii cells
      trapped by ODEP can form a micrometer-sized motor array. The rotating frequency
      of the cells ranges from 50 to 120 rpm, which can be reversibly adjusted with a
      fast response speed by varying the optical intensity. Functional flagella have
      been demonstrated to play a decisive role in the rotation. The programmable cell
      array with a rotating motion can be used as a bio-micropump to drive the liquid
      flow in microfludic chips and may shed new light on bio-actuation.

PMID- 28513723
TI  - Amphiphilic coatings for the protection of upconverting nanoparticles against
      dissolution in aqueous media.
AB  - Upconverting nanoparticles (UCNPs) of beta-NaYF4, co-doped with Yb3+ and Tm3+ and
      21-36 nm large, were synthesized using a modified thermal decomposition method.
      The as-synthesized UCNPs were coated with oleic acid and dispersed in nonpolar
      media. Their morphology, size and crystal structure were analysed with
      transmission electron microscopy and X-ray diffraction. The UCNPs showed a
      fluorescence emission spectrum characteristic of Tm3+. Their dissolution in water
      (pH ~ 4-5) and phosphate buffered saline (PBS, pH = 7.4) was determined from the
      fraction of dissolved fluoride ions using a fluoride-ion-selective electrode. The
      dissolution of bare UCNPs was much more prominent in PBS than in water. Two
      amphiphilic coatings, poly(maleic anhydride-alt-1-octadecene)
      bis(hexamethylene)triamine (PMAO-BHMT) and d-alpha-tocopheryl polyethylene glycol
      succinate (TPGS) were tested for their effects on the dissolution of the UCNPs.
      The coatings were formed directly on the as-synthesized UCNPs as was confirmed
      with electrokinetic measurements, infrared spectroscopy and thermogravimetric
      analyses. Both coatings enabled the dispersion of UCNPs in water, and improved
      the fluorescence emission intensity with respect to the bare UCNPs. However, only
      the PMAO-BHMT coating provided an effective protection against the dissolution of
      the UCNPs and long-term colloidal stability in PBS, and did not show cytotoxicity
      in EAhy926 endothelial cells.

PMID- 28513725
TI  - Push-pull type meso-ester substituted BODIPY near-infrared dyes as contrast
      agents for photoacoustic imaging.
AB  - A series of push-pull type meso-ester substituted BODIPY dyes 1-4 with intense
      near-infrared absorption, largely enhanced photoacoustic (PA) activity and
      excellent photo-stability were synthesized. The impact of the electronic
      structure on the PA activity was also discussed. Moreover, the in vitro and in
      vivo PA imaging were investigated, which suggested a passive targeting capacity
      in the tumor site.

PMID- 28513724
TI  - Role of electronic correlations in photoionization of NO2 in the vicinity of the
      2A1/2B2 conical intersection.
AB  - We present the first ab initio multi-channel photoionization calculations for NO2
      in the vicinity of the 2A1/2B2 conical intersection, for a range of nuclear
      geometries, using our newly developed set of tools based on the ab initio
      multichannel R-matrix method. Electronic correlation is included in both the
      neutral and the scattering states of the molecule via configuration interaction.
      Configuration mixing is especially important around conical intersections and
      avoided crossings, both pertinent for NO2, and manifests itself via significant
      variations in photoelectron angular distributions. The method allows for a
      balanced and accurate description of the photoionization/photorecombination for a
      number of different ionic channels in a wide range of photoelectron energies up
      to 100 eV. Proper account of electron correlations is crucial for interpreting
      time-resolved signals in photoelectron spectroscopy and high harmonic generation
      (HHG) from polyatomic molecules.

PMID- 28513726
TI  - Delocalized and localized donating-accepting Mn-C interactions in half-sandwich
      cyclopentadienyl and pentadienyl complexes.
AB  - The widely used cyclopentadienyl (Cp) ligand and the pentadienyl (Pdl) ligand
      have very similar molecular orbitals (MOs) but they have significantly different
      chemical behavior. The extensively mixing of the MOs in the Pdl ligand has
      prevented a quantitative explanation of the observed differences between these
      two ligands. In a series of synthesized close/open half sandwich manganese
      phosphine carbonyls, the quantum theory of atoms in molecules and the interacting
      quantum atom model allow us to quantify the accepting-donating capacities of both
      ligands and to break down the M-dienyl bond into individual atomic interactions.
      The Mn-Pdl bond is stronger, more localized and has a larger backbonding
      contribution than the Mn-Cp bond. All carbon atoms in the Cp ring interact
      similarly with the Mn center, whereas the Pdl's terminal carbon atoms exhibit a
      strong donor and a moderate acceptor character, and C2 and C4 have an acceptor
      character and C3 a donor character. Contrarily to the constrained five-membered
      Cp ring, the stronger Mn-Pdl interaction can barely compensate for the large
      destabilizing distortion of the backbone of the nonaromatic Pdl ligand.

PMID- 28513727
TI  - Self-assembled air-stable magnesium hydride embedded in 3-D activated carbon for
      reversible hydrogen storage.
AB  - The rational design of stable, inexpensive catalysts with excellent hydrogen
      dynamics and sorption characteristics under realistic environments for reversible
      hydrogen storage remains a great challenge. Here, we present a simple and
      scalable strategy to fabricate a monodispersed, air-stable, magnesium hydride
      embedded in three-dimensional activated carbon with periodic synchronization of
      transition metals (MHCH). The high surface area, homogeneous distribution of MgH2
      nanoparticles, excellent thermal stability, high energy density, steric
      confinement by carbon, and robust architecture of the catalyst resulted in a
      noticeable enhancement of the hydrogen storage performance. The resulting MHCH-5
      exhibited outstanding hydrogen storage performance, better than that of most
      reported Mg-based hydrides, with a high storage density of 6.63 wt% H2, a rapid
      kinetics loading in <5 min at 180  degrees C, superior reversibility, and
      excellent long-term cycling stability over ~435 h. The significant reduction of
      the enthalpy and activation energy observed in the MHCH-5 demonstrated
      enhancement of the kinetics of de-/hydrogenation compared to that of commercial
      MgH2. The origin of the intrinsic hydrogen thermodynamics was elucidated via
      solid state 1H NMR. This work presents a readily scaled-up strategy towards the
      design of realistic catalysts with superior functionality and stability for
      applications in reversible hydrogen storage, lithium ion batteries, and fuel
      cells.

PMID- 28513728
TI  - A droplet-chip/mass spectrometry approach to study organic synthesis at nanoliter
      scale.
AB  - A droplet-based microfluidic device with seamless hyphenation to electrospray
      mass spectrometry was developed to rapidly investigate organic reactions in
      segmented flow providing a versatile tool for drug development. A chip-MS
      interface with an integrated counterelectrode allowed for a flexible positioning
      of the chip-emitter in front of the MS orifice as well as an independent
      adjustment of the electrospray potentials. This was necessary to avoid
      contamination of the mass spectrometer as well as sample overloading due to the
      high analyte concentrations. The device was exemplarily applied to study the
      scope of an amino-catalyzed domino reaction with low picomole amount of catalyst
      in individual nanoliter sized droplets.

PMID- 28513729
TI  - Stable small bubble clusters in two-dimensional foams.
AB  - Key features of the mechanical response of amorphous particulate materials, such
      as foams, emulsions, and granular media, to applied stress are determined by the
      frequency and size of particle rearrangements that occur as the system
      transitions from one mechanically stable state to another. This work describes
      coordinated experimental and computational studies of bubble rafts, which are
      quasi-two dimensional systems of bubbles confined to the air-water interface. We
      focus on small mechanically stable clusters of four, five, six, and seven bubbles
      with two different sizes with diameter ratio sigmaL/sigmaS ? 1.4. Focusing on
      small bubble clusters, which can be viewed as subsystems of a larger system,
      allows us to investigate the full ensemble of clusters that form, measure the
      respective frequencies with which the clusters occur, and determine the form of
      the bubble-bubble interactions. We emphasize several important results. First,
      for clusters with N > 5 bubbles, we find using discrete element simulations that
      short-range attractive interactions between bubbles give rise to a larger
      ensemble of distinct mechanically stable clusters compared to that generated by
      long-range attractive interactions. The additional clusters in systems with short
      range attractions possess larger gaps between pairs of neighboring bubbles on the
      periphery of the clusters. The ensemble of bubble clusters observed in
      experiments is similar to the ensemble of clusters with long-range attractive
      interactions. We also compare the frequency with which each cluster occurs in
      simulations and experiments. We find that the cluster frequencies are extremely
      sensitive to the protocol used to generate them and only weakly correlated to the
      energy of the clusters.

PMID- 28513730
TI  - Accurate measurement of the chirality of WS2 nanotubes.
AB  - We describe the structural parameters and atomic positions of a single-walled WS2
      nanotube. The structure factor is calculated in detail using analytic expressions
      for both single-walled and multi-walled WS2 nanotubes. A zoning scheme has been
      developed to obtain the ratio m/n from the electron diffraction patterns. The
      procedure for determination of the chiral indices of both single-walled and multi
      walled WS2 nanotubes and the tilt angle is illustrated in detail for either
      normal incidence or inclined incidence. As an example of application, the
      determination of the chiral indices of a five-shell WS2 nanotube was carried out
      and the tilt angle was obtained as 17.7 degrees . The method developed here is
      useful and valid to determine the atomic structure of WS2 nanotubes.

PMID- 28513732
TI  - Reduced {001}-TiO2-x photocatalysts: noble-metal-free CO2 photoreduction for
      selective CH4 evolution.
AB  - The preparation of reduced TiO2 photocatalysts with high Ti3+ concentration is a
      great challenge due to their instability in air. Here we report a new approach
      for the synthesis of reduced TiO2 with {001} facets exposed via a hydrothermal
      process. By the introduction of fluoride atoms, {001} and {101} facets are
      formed, which act as hole and electron collectors, respectively, for charge
      separation. By adjusting the volume of HF added, a rutile-anatase transition is
      observed for the first time. EPR spectra confirm the generation of Ti3+ species
      in the bulk of TiO2, and Ti3+ signals are studied in the anatase and rutile
      phases separately. The quantified EPR shows that reduced TiO2 samples present 14
      000-fold more spins compared to the pristine TiO2, and the intensity can reach as
      high as 24.6 * 1019 spins per g. The obtained samples also have a unique
      disordered layer with a thickness of 1-2 nm on their surfaces, which contributes
      to the stabilization of the formed Ti3+ species by preventing their oxidation in
      air. In addition, the synthesized reduced TiO2 samples also exhibit wide-spectrum
      solar light absorption, especially in the near-infrared region. Owing to their
      enhanced solar light absorption, improved electron-hole separation and special
      facet exposure, these samples exhibit enhanced photocatalytic CO2 reduction
      performance and high CH4 selectivity under solar light irradiation, in the
      absence of a noble metal Pt as a co-catalyst.

PMID- 28513731
TI  - Ag@Au nanoprism-metal organic framework-based paper for extending the glucose
      sensing range in human serum and urine.
AB  - In this work, we present a Ag@Au nanoprism-metal-organic framework-paper based
      glucose sensor for rapid, sensitive, single-use and quantitative glucose
      determination in human serum. To achieve painless measurement of glucose with a
      non-invasive detection methodology, this biosensor was further tested in human
      urine. In this approach, a new hybrid-Ag@Au nanoprism loaded in close proximity
      to micrometer sized coordination polymers as phosphorescent luminophores
      significantly enhanced the emission intensity due to metal-enhanced
      phosphorescence and worked as reaction sites to support more dissolved oxygen.
      Reports of enhanced phosphorescence intensity are relatively rare, especially at
      room temperature. The true enhancement factor of Ag@Au-phosphorescent metal
      organic frameworks on paper was deduced to be 110-fold, making it a better
      optical type glucose meter. The results demonstrate the validity of the intensity
      enhancement effect of the excitation of the overlap of the emission band of a
      luminophore with the surface plasmon resonance band of Ag@Au nanoprisms. Ag@Au
      nanoprisms were used not only to improve the detection limit of glucose sensing
      but also to extend the glucose sensing range by enhancing the oxygen oxidation
      efficiency. The oxidation of glucose as glucose oxidase is accompanied by oxygen
      consumption, which increases the intensity of the phosphorescence emission. The
      turn-on type paper-based biosensor exhibits a rapid response (0.5 s), a low
      detection limit (0.038 mM), and a wide linear range (30 mM to 0.05 mM), as well
      as good anti-interference, long-term longevity and reproducibility. Finally, the
      biosensor was successfully applied to the determination of glucose in human serum
      and urine.

PMID- 28513733
TI  - Polylactic acid nano- and microchamber arrays for encapsulation of small
      hydrophilic molecules featuring drug release via high intensity focused
      ultrasound.
AB  - Long term encapsulation combined with spatiotemporal release for a precisely
      defined quantity of small hydrophilic molecules on demand remains a challenge in
      various fields ranging from medical drug delivery, controlled release of
      catalysts to industrial anti-corrosion systems. Free-standing individually sealed
      polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip
      coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient
      conditions. The wall thickness of these hydrophobic nano-microchambers is tunable
      from 150 nm to 7 MUm by varying the PLA solution concentration. Furthermore,
      small hydrophilic molecules were successfully in situ precipitated within
      individual microchambers in the course of solvent evaporation after sonicating
      the PLA@PDMS stamp to remove air-bubbles and to load the active substance
      containing solvent. The cargo capacity of single chambers was determined to be in
      the range of several picograms, while it amounts to several micrograms per cm2.
      Two different methods for sealing chambers were compared: microcontact printing
      versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for
      entrapment of micro-air-bubbles enabling microchambers with both ultrasound
      responsiveness and reduced permeability. Cargo release triggered by external high
      intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and
      compared with numerical simulations.

PMID- 28513734
TI  - Strained alkynes derived from 2,2'-dihydroxy-1,1'-biaryls; synthesis and copper
      free cycloaddition with azides.
AB  - A series of strained alkynes were prepared from 2,2'-dihydroxy-biaryls. Several
      were characterised by X-ray crystallography, revealing strained C(sp)-C(sp)
      C(sp3) bond angles in the range of 163-167 degrees . Their cycloadditions with
      azides proceed without a catalyst. Functionalised versions of these reagents have
      potential applications to materials synthesis and bioconjugations.

PMID- 28513735
TI  - Highly efficient genome editing of human hematopoietic stem cells via a nano
      silicon-blade delivery approach.
AB  - Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)
      Cas9 bacterial immunity system has opened a promising avenue to treat genetic
      diseases that affect the human hematopoietic stem cells (HSCs). Therefore,
      finding a highly efficient delivery method capable of modifying the genome in the
      hard-to-transfect HSCs, combined with the advanced CRISPR-Cas9 system, may meet
      the challenges for dissecting the hematologic disease mechanisms and facilitate
      future clinical applications. Here, we developed an effective HSC-specified
      delivery microfluidic chip to disrupt the cell membrane transiently by inducing
      rapid mechanical deformation that allowed the delivery of biomaterials into the
      cytoplasm from the surrounding matrix. Compared with the previous designs, the
      new nano-silicon-blade structure was specifically optimized for HSCs. Using the
      silicon substrate, the sharpness and rigidity of the nano-blade constriction was
      largely enhanced to improve the biomaterials delivery efficiency. We achieved
      highly efficient delivery results by transporting various macro-molecules into
      the HSCs. Moreover, the treated HSCs possess high viability and maintain inherent
      pluripotency after the delivery via the Nano-Blade Chip (NB-Chip). Subsequently,
      we disrupted the p42 isoform in C/EBPalpha on the NB-Chip and induced HSCs into a
      myeloid proliferation behavior. In conclusion, the NB-Chip provides a harmless,
      rapid and high-throughput gene editing approach for the HSC study and
      therapeutics.

PMID- 28513736
TI  - Photosensitization of CuI - the role of visible light induced CuI-> CuII
      transition in photocatalytic degradation of organic pollutants and inactivation
      of microorganisms.
AB  - Bare and photosensitized copper iodides were tested in photocatalysed degradation
      of an organic dye (Acid Red 1) and inactivation of fungi (Saccharomyces
      cerevisiae). CuI, with the band gap energy slightly lower than that of TiO2,
      appeared to be highly efficient in these processes. Sensitization of copper
      iodide was achieved by surface modification with [Cu(SCN)2(phen)2]. The
      photosensitization mechanism encompasses a metal to metal charge transfer, CuI->
      CuII. The applied photosensitizer binds to CuI through thiocyanate ligands
      resulting in the formation of an active CuII/CuI hybrid photocatalyst
      ([CuII(SCN)2(phen)2]@CuII). Its absorption edge is red shifted towards a lower
      energy when compared with bare CuI, resulting in enhanced visible light induced
      photocatalytic activity. The studied materials appeared to be photoactive in
      current generation, degradation of organic compounds and inactivation of fungi.

PMID- 28513738
TI  - Role of Ni in hetero-architectured NiO/Ni composites for enhanced catalytic
      performance.
AB  - A facile, one-step combustion synthesis in solution is reported for preparing
      hetero-architectured NiO/Ni nanocomposites using different organic fuels. The
      prepared nanocomposites were physicochemically characterized for crystal
      structure, functional groups, and morphology. It was found that the content of Ni
      in the nanocomposite varied due to different combustion fuels. A photocatalytic
      (PC) investigation of these nanocomposites was performed using rhodamine 6G (RG)
      under UV light. A citric acid combusted NiO/Ni (N-CA) composite containing 20% Ni
      phase showed the highest photoactivity in comparison to pure NiO due to its large
      porous channels and high surface area (~28 +/- 2 m2 g-1). The N-CA catalyst was
      further evaluated for the degradation of cationic, anionic dyes and chloro/nitro
      phenols under both UV and visible light. Photoelectrocatalysis (PEC) of RG with N
      CA resulted in complete degradation of the dye. The mechanism governing the
      catalytic processes was determined from the trapping experiments. The potential
      reasons for the enhanced photoactivity of the NiO/Ni nanocomposite were that Ni
      acted as an electron sink, and the applied bias of +1.0 V separated the electron
      hole, reducing its rate of recombination.

PMID- 28513737
TI  - Dimeric and trimeric derivatives of the azinomycin B chromophore show enhanced
      DNA binding.
AB  - To explore the utility of the azinomycin B chromophore as a platform for the
      development of major-groove binding small molecules, we have prepared a series of
      3-methoxy-5-methylnaphthalene derivatives containing diamine, triamine, and
      carbohydrate linker moieties. All bis- and tris-azinomycin derivatives are
      intercalators that display submicromolar binding affinities for calf-thymus DNA,
      as revealed by viscometry measurements and fluorescent intercalator displacement
      (FID) assays, respectively. Although the tightest binding ligand 1d (Ka = 2.42 *
      107 M-1) has similar affinities for sequence diverse polynucleotides, competition
      binding studies with methylated phage DNA and known major and minor groove
      binding small molecules suggest that the tether moiety linking the naphthalene
      chromophores may occupy the major groove of DNA.

PMID- 28513739
TI  - Vapour-liquid interfacial properties of square-well chains from density
      functional theory and Monte Carlo simulation.
AB  - The statistical associating fluid theory for attractive potentials of variable
      range (SAFT-VR) density functional theory (DFT) developed by [Gloor et al., J.
      Chem. Phys., 2004, 121, 12740-12759] is used to predict the interfacial behaviour
      of molecules modelled as fully-flexible square-well chains formed from
      tangentially-bonded monomers of diameter sigma and potential range lambda =
      1.5sigma. Four different model systems, comprising 4, 8, 12, and 16 monomers per
      molecule, are considered. In addition to that, we also compute a number of
      interfacial properties of molecular chains from direct simulation of the vapour
      liquid interface. The simulations are performed in the canonical ensemble, and
      the vapour-liquid interfacial tension is evaluated using the wandering interface
      (WIM) method, a technique based on the thermodynamic definition of surface
      tension. Apart from surface tension, we also obtain density profiles, coexistence
      densities, vapour pressures, and critical temperature and density, paying
      particular attention to the effect of the chain length on these properties.
      According to our results, the main effect of increasing the chain length (at
      fixed temperature) is to sharpen the vapour-liquid interface and to increase the
      width of the biphasic coexistence region. As a result, the interfacial thickness
      decreases and the surface tension increases as the molecular chains get longer.
      The interfacial thickness and surface tension appear to exhibit an asymptotic
      limiting behaviour for long chains. A similar behaviour is also observed for the
      coexistence densities and critical properties. Agreement between theory and
      simulation results indicates that SAFT-VR DFT is only able to predict
      qualitatively the interfacial properties of the model. Our results are also
      compared with simulation data taken from the literature, including the vapour
      liquid coexistence densities, vapour pressures, and surface tension.

PMID- 28513740
TI  - l-Ornithine stimulates growth hormone release in a manner dependent on the
      ghrelin system.
AB  - We found that intraduodenal administration of l-ornithine (l-Orn) stimulates
      growth hormone (GH) secretion in Wistar rats, and then investigated its
      mechanism. GH-releasing activity after intraduodenal administration of l-Orn was
      blocked by [d-Lys3]-GHRP-6, an antagonist of the ghrelin receptor; however, l-Orn
      (100 MUM) has no affinity for the ghrelin receptor, suggesting that the GH
      releasing activity of l-Orn is mediated via ghrelin release and activation of the
      ghrelin receptor. Intraduodenally administered l-Orn increased ghrelin mRNA
      expression in the duodenum but not in the stomach or hypothalamus. In addition, l
      Orn-induced GH-releasing activity was inhibited by propranolol, an antagonist of
      beta-adrenergic receptor, which is known to be coupled to ghrelin release. In
      conclusion, intraduodenally administered l-Orn stimulates GH secretion through
      the sympathetic nervous and ghrelin systems.

PMID- 28513741
TI  - Magneto-structural correlations in a family of di-alkoxo bridged chromium dimers.
AB  - A series of di-alkoxo bridged Cr(iii) dimers have been synthesised using pyridine
      alcohol ligands. The structures fall into four general categories and are of
      formula: [Cr2(OMe)2(pic)4].1/2MeOH.1/2Et2O (1), [Cr2(hmp)2(pic)2X2] (where X = Cl
      (2), Br (3)), [Cr2(L)2Cl4(A)2].2S (where L = hmp, A = H2O and S = Et2O (4); L =
      hmp, A = pyridine and S = pyridine (5); L = hmp, A = 4-picoline and no S (6); L =
      hep, A = H2O and S = MeCN (7)), and [Cr(hmp)(hmpH)Cl2].MeCN (8). Direct current
      (DC) magnetic susceptibility measurements show relatively weak antiferromagnetic
      exchange interactions between the Cr(iii) centres with J values <|15| cm-1 in all
      of the complexes measured. DFT calculations performed on complexes 1-8 reproduce
      both the sign and strength of the exchange interactions found experimentally, and
      confirm that the magnitude and sign of the J value is strongly dependent upon the
      orientation of the dihedral angle formed between the bridging Cr2O2 plane and the
      O-R vector of the bridging group (theta), and the Cr-O-Cr-O dihedral angle (psi).

PMID- 28513742
TI  - Structural stability and intriguing electronic properties of two-dimensional
      transition metal dichalcogenide alloys.
AB  - Based on the first-principles calculations, we systematically studied the
      structures and electronic properties of two-dimensional (2D) transition metal
      dichalcogenide (TMD) alloys with half-to-half mixing of S and Se. Using the
      chemical potentials of S and Se, the energetic phase diagrams for both single
      phases and mixed phases of TMD were constructed. A new heterolayer structure (for
      Sc and Ti) and alternating structure (for Cr, Mn, Fe, Zr, Mo, and W) were
      proposed for the first time, which were thermodynamically stable for MSSe alloys
      under the S-poor (relatively low chemical potential of S) and Se-rich (relatively
      high chemical potential of Se) conditions, and further compared with the
      disordered structures. Moreover, band gaps, carrier effective mass, and work
      functions were calculated for these stable mixed phases. Compared to the single
      phases of MS2 and MSe2, MSSe alloys showed superior electronic properties
      including tunable band gaps and work functions. Importantly, the significantly
      reduced effective mass of the carriers in the MSSe alloys may induce higher
      carrier mobility, providing better performance of TMD materials in electronic
      devices.

PMID- 28513743
TI  - Adsorption differences between low coverage enantiomers of alanine on the chiral
      Cu{421}R surface.
AB  - Chiral separation using heterogeneous methods has long been sought after. Chiral
      metal surfaces have the potential to make it possible to model these systems
      using small amino acids, the building blocks for proteins. A comparison of
      submonolayer concentrations of alanine enantiomers adsorbed onto Cu{421}R has
      revealed a large geometrical differences between the two molecules as compared to
      the saturated coverage. Large differences were observed in HR-XPS and NEXAFS and
      complemented by theoretical DFT calculations. At approximately one third of a
      monolayer a comparison of the C1s XPS signal showed a shift in the methyl group
      of more than 300 meV indicating that the two enantiomers are in different
      chemical environments. NEXAFS spectroscopy confirmed the XPS variations and
      showed large differences in the orientation of the adsorbed molecules. Our DFT
      results show that the l-enantiomer is energetically the most stable in the {311}
      microfacet configuration. In contrast to the full monolayer coverage, these lower
      coverages showed enhanced selectivity.

PMID- 28513744
TI  - High-affinity recognition of the human C-reactive protein independent of
      phosphocholine.
AB  - A high-affinity polypeptide conjugate 4-C25L22-DQ, has been developed for the
      molecular recognition of the human C-reactive protein, CRP, a well-known
      inflammation biomarker. CRP is one of the most frequently quantified targets in
      diagnostic applications and a target in drug development. With the exception of
      antibodies, most molecular constructs take advantage of the known affinity for
      CRP of phosphocholine that depends on Ca2+ for its ability to bind. 4-C25L22-DQ
      which is unrelated to phosphocholine binds in the absence of Ca2+ with a
      dissociation constant of 760 nM, an order of magnitude lower than that of
      phosphocholine, the KD of which is 5 MUM. The small organic molecule 2-oxo-1,2
      dihydroquinoline-8-carboxylic acid (DQ) was designed based on the structural
      similarities between three hits from a set of compounds selected from a building
      block collection and evaluated with regards to affinity for CRP by NMR
      spectroscopy. 4-C25L22-DQ was shown in a competition experiment to bind CRP three
      orders of magnitude more strongly than DQ itself, and in a pull-down experiment 4
      C25L22-DQ was shown to extract CRP from human serum. The development of a robust
      and phosphocholine-independent recognition element provides unprecedented
      opportunities in bioanalytical applications in vivo and in vitro under conditions
      where the concentration of Ca2+ ions is low, or where Ca2+ binding agents such as
      EDTA or heparin are needed to prevent blood coagulation. The identification from
      a compound library of a small organic molecule and its conjugation to a small set
      of polypeptides, none of which were previously known to bind CRP, illustrates a
      convenient and general route to selective high-affinity binders for proteins with
      dissociation constants in the MUM to nM range for which no small molecule ligands
      are known.

PMID- 28513745
TI  - In vivo fermentation of a Pleurotus eryngii polysaccharide and its effects on
      fecal microbiota composition and immune response.
AB  - A novel, homogeneous Pleurotus eryngii polysaccharide (PEP) (molecular weight 426
      kDa, purity 91.25 +/- 3.14%) which mainly consisted of glucose with beta-type
      glycosidic linkages was used to investigate in vivo fermentation behavior and
      effects on immune response in mice. Different doses (0.2, 0.4, 0.8 g per kg body
      weight) were orally administered to the mice for a period of six weeks. The
      results showed that the SCFA concentration, pH value, and moisture contents of
      cecum and colon contents were significantly altered with high-dose PEP treatment
      compared to the control group (P < 0.05). Moreover, the fecal microbiota in the
      PEP treated group was found to be structurally different compared to the control
      group; especially, the Porphyromonadaceae, Rikenellaceae, Bacteroidaceae and
      Lactobacillaceae abundances were all increased at the family level. In addition,
      the exerted immune response was significantly altered after the high-dose PEP
      oral administration. This exploratory study indicated that intake of PEP could
      have a positive role in gastrointestinal tract health.

PMID- 28513746
TI  - Structure-functionality relationship and pharmacological profiles of Pseudomonas
      aeruginosa alkylquinolone quorum sensing modulators.
AB  - An important paradigm in anti-infective research is the antivirulence concept.
      Pathoblockers are compounds which disarm bacteria of their arsenal of virulence
      factors. PqsR is a transcriptional regulator controlling the production of such
      factors in Pseudomonas aeruginosa, most prominently pyocyanin. In this work, a
      series of tool compounds based on the structure of the natural ligand 2-heptyl-4
      quinolone (HHQ) were used for probing the structure-functionality relationship.
      Four different profiles are identified namely agonists, antagonists, inverse
      agonists and biphasic modulators. Molecular docking studies revealed that each
      class of the PqsR modulators showed distinctive interactions in the PqsR binding
      domain. It was found that the substituents in position 3 of the quinolone core
      act as a switch between the different profiles, according to their ability to
      donate or accept a hydrogen bond, or form a hydrophobic interaction. Finally, it
      was shown that only inverse agonists were able to strongly inhibit pyocyanin
      production.

PMID- 28513747
TI  - Structural and electronic elucidation of a N-heterocyclic silylene vanadocene
      adduct.
AB  - The solid and solution state structure of the vanadium(ii) N-heterocyclic
      silylene (NHSi) complex, [(SiIPr)V(Cp)2] (1) is reported (SiIPr: 1,3-bis(2,6
      diisopropylphenyl)-1,3-diaza-2-silacyclopent-4-en-2-ylidene). The electronic
      structure of 1 is probed using a combination of magnetic measurements, EPR
      spectroscopy and computational studies. The V-Si bond strength and complex
      forming mechanism between vanadocene and an NHSi ligand is elucidated using
      computational methods.

PMID- 28513748
TI  - Development of stable Pickering emulsions/oil powders and Pickering HIPEs
      stabilized by gliadin/chitosan complex particles.
AB  - In this paper, we demonstrate the use of gliadin/chitosan complex particles
      (GCCPs) as particulate stabilizers of oil-in-water emulsions of natural oils and
      water. For this purpose, we fabricated GCCPs through a facile anti-solvent
      procedure and demonstrated their usage in the formation of Pickering emulsions
      and Pickering high internal phase emulsions (HIPEs). The GCCPs can be used to
      produce surfactant-free o/w Pickering emulsions and Pickering HIPEs;
      unfortunately these emulsions were labile to coalescence. NaCl addition and/or pH
      regulation, and the combination were used to modify the surface wettability of
      the complex particles to achieve stable emulsions. The microstructures, e.g.,
      interfacial frameworks, GCCP partition between the continuous phase and
      interfacial region, and the state of the droplets, of Pickering emulsions were
      visualized by confocal laser scanning microscopy (CLSM), confirming that the
      inclusion of NaCl and slightly adjusting pH toward 4.0 and/or 5.0 benefited the
      adsorption and accumulation of colloid particles at the droplet surface to form
      an engineered interfacial structure, bridging droplets together through a
      percolating layer of colloidal particles at the oil/water interface. A schematic
      representation for the formation route of the emulsions is proposed to relate the
      physical performance and rheological property with the interfacial structures and
      aggregate behaviors in the Pickering system stabilized by the complex particles.
      Interestingly, direct freeze-drying of the emulsions transformed unstable
      Pickering emulsions into stable oil powders. This study opens a promising route
      based on Pickering HIPEs or oil powders to structure liquid oils into solid-like
      fats without artificial trans-fat, which outlines new directions for future
      fundamental research.

PMID- 28513749
TI  - Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in
      Pseudomonas aeruginosa resistance to beta-lactam antibiotics.
AB  - The synthesis of a series of d-gluco-like configured 4,5,6-trihydroxyazepanes
      bearing a triazole, a sulfonamide or a fluorinated acetamide moiety at C-3 is
      described. These synthetic derivatives have been tested for their ability to
      selectively inhibit the muropeptide recycling glucosaminidase NagZ and to thereby
      increase sensitivity of Pseudomonas aeruginosa to beta-lactams, a pathway with
      substantial therapeutic potential. While introduction of triazole and sulfamide
      groups failed to lead to glucosaminidase inhibitors, the NHCOCF3 analog proved to
      be a selective inhibitor of NagZ over other glucosaminidases including human O
      GlcNAcase and lysosomal hexosaminidases HexA and B.

PMID- 28513750
TI  - Enantioselective magnesium-catalyzed transformations.
AB  - This review updates the major progress in the field of enantioselective
      transformations promoted by chiral magnesium catalysts, covering the literature
      since 2007, illustrating the power of these mild Lewis acid catalysts to provide
      a wide variety of novel asymmetric reactions.

PMID- 28513751
TI  - Iodine-mediated synthesis of sulfur-bridged enaminones and chromones via double
      C(sp2)-H thiolation.
AB  - The reactions of various enaminones with elemental sulfur giving rise to both
      sulfur-bridged enaminones and chromones have been realized via iodine promotion.
      All products were furnished by means of double C(sp2)-H bond thiolation without
      using any metal catalyst or sensitive oxidant, providing a simple and efficient
      protocol for the synthesis of diverse sulfur derivatives of enaminones.

PMID- 28513752
TI  - Comparison of PM2.5 carbonaceous pollutants between an urban site in Shanghai and
      a background site in a coastal East China Sea island in summer: concentration,
      composition and sources.
AB  - Nine paired samples of atmospheric particulate matter with an aerodynamic
      diameter less than or equal to 2.5 MUm (PM2.5) were collected concurrently from
      an urban site in Shanghai, China and a background site in Huaniao Island (HNI) in
      the coastal East China Sea (ECS) between July 21 and 29, 2011. The samples were
      analyzed for 16 United States Environmental Protection Agency (USEPA) priority
      polycyclic aromatic hydrocarbons (PAHs), n-alkanes (20 species, C14-C33), hopanes
      (10 species, C29-C32), and steranes (12 species, C27-C29). These two sites,
      approximately 66 km apart, are both on the pathway of land-based pollutants as
      they are transported to the ECS by seasonal winds. As expected, concentrations in
      Shanghai were higher (average: 8.4 and 67.8 ng m-3 for the 16 PAHs and n-alkanes,
      respectively) than those in HNI (average: 1.8 and 8.5 ng m-3, respectively). The
      dominant contributor to the 16 PAHs in Shanghai was 5-6-ring PAHs (60.0%),
      whereas 2-3-ring PAHs contributed the most (72.5%) in HNI. Plant waxes
      contributed 45.7% and 25.9% of the n-alkanes in Shanghai and HNI, respectively,
      implying a relatively greater contribution from petroleum residues to the n
      alkanes in HNI. Principal component analysis (PCA) and the compositions of
      hopanes and steranes highlighted a prominent contribution from traffic emissions
      to carbonaceous PM2.5 aerosols. This study provides comprehensive details about
      the sources, formation, and transport of pollutants from eastern China to the
      coastal ECS.

PMID- 28513753
TI  - Two-step conversion of carboxylic esters into distally fluorinated ketones via
      ring cleavage of cyclopropanol intermediates: application of sulfinate salts as
      fluoroalkylating reagents.
AB  - Tertiary cyclopropanols easily available from carboxylic esters have been used in
      the synthesis of distally fluorinated ketones. Cyclopropane ring cleavage
      reactions in methanol with aqueous tert-butyl hydroperoxide in the presence of a
      copper(ii) acetate catalyst and sodium triflinate (Langlois reagent) afford beta
      trifluoromethyl ketones in 16-74% isolated yields. Sodium triflinate serves as a
      precursor of reactive trifluoromethyl copper species, enabling ring-opening
      trifluoromethylation, as evidenced by mechanistic studies. We also demonstrate
      here that other sulfinate salts, such as sodium 1,1-difluoroethanesulfinate,
      sodium 2-(4-bromophenyl)-1,1-difluoroethanesulfinate and sodium 1
      (trifluoromethyl)cyclopropanesulfinate, can be used as fluoroalkylation reagents,
      resulting in the corresponding fluorinated ketones.

PMID- 28513754
TI  - Structural heterogeneity in a parent ground-state structure of AnPixJg2 revealed
      by theory and spectroscopy.
AB  - We investigated the red absorbing, dark stable state (Pr state) of the second GAF
      domain of the cyanobacteriochrome AnPixJ (AnPixJg2) by a molecular dynamics
      simulation of 1 MUs duration. Our results reveal two distinct conformational
      isoforms of the chromophore, from which only one was known from crystallographic
      experiments. The interconversion between both isoforms is accompanied by
      alterations in the hydrogen bond pattern between the chromophore and the protein
      and the solvation structure of the chromophore binding pocket. The existence of
      sub-states in the Pr form of AnPixJg2 is supported by the results from
      experimental 13C MAS NMR spectroscopy. Our finding is consistent with the
      observation of structural heterogeneity in other cyanobacteriochromes and
      phytochromes.

PMID- 28513756
TI  - Divergent synthesis of biflavonoids yields novel inhibitors of the aggregation of
      amyloid beta (1-42).
AB  - Biflavonoids are associated with a variety of biologically useful properties.
      However, synthetic biflavonoids are poorly explored within drug discovery. There
      is considerable structural diversity possible within this compound class and
      large regions of potentially biologically relevant biflavonoid chemical space
      remain untapped or underexplored. Herein, we report the development of a modular
      and divergent strategy towards biflavonoid derivatives which enabled the step
      economical preparation of a structurally diverse collection of novel unnatural
      biflavonoids. Preliminary studies established that the strategy could also be
      successfully extended to the preparation of very rare triflavonoids, which are
      also expected to be useful tools for biological intervention. Prompted by
      previous inhibitory studies with flavonoid libraries, amyloid anti-aggregation
      screening was performed, which led to the identification of several structurally
      novel inhibitors of the aggregation of the amyloid beta peptide (Abeta42).
      Aggregated Abeta42 is a pathological hallmark of Alzheimer's disease and the use
      of small molecules to inhibit the aggregation process has been identified as a
      potentially valuable therapeutic strategy for disease treatment. Methylated
      biaurones were associated with highest levels of potency (the most active
      compound had an IC50 value of 16 MUM), establishing this scaffold as a starting
      point for inhibitor development.

PMID- 28513755
TI  - Re-assembled casein micelles improve in vitro bioavailability of vitamin D in a
      Caco-2 cell model.
AB  - The pandemic of vitamin D (VD) deficiency, and the global rise in obesity
      stimulate a need for staple low-fat foods and beverages enriched with VD. In
      light of consumer demand for a clean label, the use of natural endogenous food
      ingredients as delivery vehicles is of great interest. To this end, re-assembled
      casein micelles (rCM) have been shown to help retain VD during processing and
      shelf life and provide high bioavailability in low-fat milk and non-fat yoghurt.
      This follow-up study focused on the performance of VD-loaded rCM after drying and
      reconstitution, considering VD retention during simulated digestion, and the
      subsequent in vitro bioavailability of the vitamin. rCM conferred great
      protection to VD3 during simulated digestion with a significant increase in
      vitamin retention for 1 h under gastric conditions. This observation is believed
      to arise from the vitamin-casein binding and the system's natural gelation (curd
      formation) near the casein isoelectric point that seclude the vitamin from
      environmental stressors and couple its release with digestive proteolysis of the
      rCM matrix. Vitamin absorption by Caco-2 cells from digested rCM was not
      significantly different from the absorption of the digested free VD. However,
      thanks to the highly protective effect of the rCM, against VD gastric
      degradation, the overall effect of the rCM was a 4-fold higher bioavailability,
      compared to the free VD.

PMID- 28513757
TI  - [New drugs for horses and production animals in 2016].
AB  - In 2016, only one newly developed active pharmaceutical ingredient for horses and
      food-producing animals was released on the German market for veterinary drug
      products. The immunomodulator Pegbovigrastim is now available as an injection
      solution for cattle (Imrestor(r)). Four established veterinary active
      pharmaceutical ingredients are available for further species: the ectoparasitic
      Amitraz (Apitraz(r)) from the triazapentadiene group was additionally authorized
      for honeybees, the expectorant Bromhexine (Exflow(r) Vet) for chickens, turkeys
      and ducks and the macrolide antibiotic Gamithromycin (Zactran(r)) for pigs. The
      dopamine D2 receptor agonist Cabergolin (Velactis(r)) was released for dairy
      cattle. However, the authorization was suspended a few months after market
      introduction because of severe side effects. Additionally, one veterinary drug
      with a new combination of active ingredients as well as one active substance in
      mono-preparation have been launched on the market for horses and food producing
      animals.

PMID- 28513758
TI  - [New drugs for small animals in 2016].
AB  - In 2016, two active pharmaceutical ingredients were released on the German market
      for small animals: the mineralocorticoid Desoxycorticosterone (Zycortal(r)) and
      Sarolaner (Simparica(r)), an ectoparasiticide of the isoxazoline group. One
      substance has been authorized for an additional species; Fluralaner
      (Bravecto(r)), also an ectoparasiticide of the isoxazoline group, is now
      authorized for use in cats. Additionally, one veterinary drug with a new
      combination of active ingredients, one active substance in mono-preparation and
      two veterinary drugs with a new pharmaceutical form have been launched on the
      market for small animals.

PMID- 28513759
TI  - [Diagnosis of leptospirosis in dogs].
AB  - Rapid confirmation of the diagnosis leptospirosis is important in order to apply
      appropriate treatment; in addition, infected dogs are a zoonotic risk. Culture
      and isolation of living leptospires from blood, urine, or tissues is considered
      the reference standard of diagnosis. However, sensitivity are low, and
      leptospires require weeks to months to grow. Therefore, diagnosis of
      leptospirosis is most commonly based on antibody testing or the detection of
      Leptospira spp. DNA by PCR. Microscopic agglutination test (MAT) is currently
      still the recommended confirmatory test for canine leptospirosis, despite its
      numerous limitations (e. g., negative results in early infection, positive
      results due to vaccine-associated antibodies). ELISA can differentiate between
      IgG and IgM antibodies and thus, discriminate current infections from previous
      vaccination or exposure. Point-of-care tests and in-house-PCR tests have recently
      been developed for use in private practice allowing easy and immediate diagnosis.
      However, only few data on sensitivity and specificity of these tests exist so
      far. A reliable diagnosis can only be established in case of a positive PCR
      result or a fourfold titre increase in MAT.

PMID- 28513760
TI  - Cell therapy in the treatment of bipolar mania in an animal model: a proof of
      concept study.
AB  - INTRODUCTION: The rationale of mesenchymal stem cells (MSCs) as a novel
      therapeutic approach in certain neurodegenerative diseases is based on their
      ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar
      disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the
      development of new strategies to stimulate the neurogenesis process in BD is
      crucial. OBJECTIVES: To investigate the behavioral and neurochemical changes
      induced by transplantation of MSCs in a model of mania-like behavior induced by
      lisdexamfetamine dimesylate (LDX). METHODS: Wistar rats (n=65) received one oral
      daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment,
      the animals additionally received intrahippocampal saline or MSC (1 uL containing
      25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two
      hours after the last administration, behavioral and neurochemical analyses were
      performed. RESULTS: LDX-treated rats had increased locomotor activity compared to
      saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive
      behavior (p<0.001). In contrast, the administration of MSCs did not change
      hyperlocomotion, indicating no effects of this treatment on LDX-treated rats
      (p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in
      the hippocampus of rats. CONCLUSION: Even though these results suggest that a
      single intrahippocampal injection of MSCs was not helpful to treat hyperactivity
      induced by LDX and neither influenced BDNF secretion, we cannot rule out the
      possible therapeutic effects of MSCs. Further research is required to determine
      direct effects of LDX on brain structures as well as in other pathophysiological
      targets related to BD.

PMID- 28513762
TI  - Water fluoridation in Brazilian cities at the first decade of the 21st century.
AB  - OBJECTIVE: To assess the coverage of the fluoridation of the public water supply
      in Brazilian municipalities at the first decade of the 21st century, according to
      population size and municipal human development index (MHDI). METHODS: We have
      used data produced by national information agencies and the United Nations
      Development Programme. Population size was separated into < 10,000, 10,000
      50,000, and > 50,000 inhabitants. The MHDI was classified into < 0.600, 0.600
      0.699, 0.700-0.799, and > 0.799. Absolute and relative inequalities between
      categories were evaluated using indicators of effect and total impact. RESULTS:
      We have obtained information for 5,558 municipalities. The coverage rate of water
      fluoridation increased from 67.7% to 76.3%. Approximately 884 (15.9%)
      municipalities and 29,600,000 inhabitants started being benefited by the measure.
      We have observed a significant expansion in municipalities with < 10,000
      inhabitants (increase of 21.0 percentage points) and low or very low MHDI (17.7
      percentage points). CONCLUSIONS: Population coverage of the public policy has
      increased 8.6%, and we can also see significant reductions in absolute and
      relative inequality according to population size and MHDI. Regarding municipal
      coverage rate, there was also a reduction in inequality in all comparisons except
      for absolute inequality between the categories of MHDI. The public policy has
      operated as a factor of health protection in the context of the ongoing social
      protection policies in the country. OBJETIVO: Avaliar a cobertura da fluoretacao
      da agua de abastecimento publico em municipios brasileiros na primeira decada do
      seculo XXI, segundo porte demografico e nivel de desenvolvimento humano municipal
      (IDH-M). METODOS: Foram utilizados dados produzidos por agencias nacionais de
      informacao e pelo Programa das Nacoes Unidas para o Desenvolvimento. O porte
      demografico foi separado em < 10 mil; 10-50 mil; > 50 mil habitantes. O IDH-M foi
      classificado em < 0,600; 0,600-0,699; 0,700-0,799; > 0,799. As desigualdades
      absoluta e relativa entre as categorias foram avaliadas por meio de indicadores
      de efeito e de impacto total. RESULTADOS: Foram obtidas informacoes para 5.558
      municipios. A taxa de cobertura da fluoretacao da agua aumentou de 67,7% para
      76,3%. Passaram a ser beneficiados pela medida 884 (15,9%) municipios, e 29,6
      milhoes de habitantes. Observou-se ampliacao expressiva em municipios com < 10
      mil habitantes (aumento de 21,0 pontos percentuais) e com IDH-M baixo ou muito
      baixo (17,7 pontos percentuais). CONCLUSOES: A cobertura populacional da politica
      publica aumentou 8,6%, sendo expressivas as reducoes das desigualdades absoluta e
      relativa segundo o porte demografico e o IDH-M. Quanto a taxa de cobertura
      municipal, houve tambem reducao da desigualdade em todas as comparacoes com
      excecao da desigualdade absoluta entre as categorias de IDH-M. A politica publica
      operou como fator de protecao sanitaria no contexto das politicas de protecao
      social em curso no pais.

PMID- 28513761
TI  - Socioeconomic determinants of access to health services among older adults: a
      systematic review.
AB  - OBJECTIVE: The objective of this study was to analyze the association between the
      socioeconomic characteristics and the access to or use of health services among
      older adults. METHODS: This is a systematic review of the literature. The search
      has been carried out in the databases PubMed, LILACS and Web of Science, without
      restriction of dates and languages; however we have included only articles
      published in Portuguese, English, and Spanish. The inclusion criteria were:
      observational design, socioeconomic factors as variables of interest in the
      analysis of the access to or use of health services among older adults,
      representative sample of the target population, adjustment for confounding
      factors, and no selection bias. RESULTS: We have found 5,096 articles after
      deleting duplicates and 36 of them have been selected for review after the
      process of reading and evaluating the inclusion criteria. Higher income and
      education have been associated with the use and access to medical appointments in
      developing countries and some developed countries. The same association has been
      observed in dental appointments in all countries. Most studies have shown no
      association between socioeconomic characteristics and the use of inpatient and
      emergency services. We have identified greater use of home visits in lower-income
      individuals, with the exception of the United States. CONCLUSIONS: We have
      observed an unequal access to or use of health services in most countries,
      varying according to the type of service used. The expansion of the health care
      coverage is necessary to reduce this unequal access generated by social
      inequities.

PMID- 28513764
TI  - Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian
      urban area.
AB  - OBJECTIVE: To analyze the determinants for the occurrence of human visceral
      leishmaniasis linked to the conditions of vulnerability. METHODS: This is an
      ecological study, whose spatial analysis unit was the Territorial Analysis Unit
      in Araguaina, State of Tocantins, Brazil, from 2007 to 2012. We have carried out
      an analysis of the sociodemographic and urban infrastructure situation of the
      municipality. Normalized primary indicators were calculated and used to construct
      the indicators of vulnerability of the social structure, household structure, and
      urban infrastructure. From them, we have composed a vulnerability index. Kernel
      density estimation was used to evaluate the density of cases of human visceral
      leishmaniasis, based on the coordinates of the cases. Bivariate global Moran's I
      was used to verify the existence of spatial autocorrelation between the incidence
      of human visceral leishmaniasis and the indicators and index of vulnerability.
      Bivariate local Moran's I was used to identify spatial clusters. RESULTS: We have
      observed a pattern of centrifugal spread of human visceral leishmaniasis in the
      municipality, where outbreaks of the disease have progressively reached central
      and peri-urban areas. There has been no correlation between higher incidences of
      human visceral leishmaniasis and worse living conditions. Statistically
      significant clusters have been observed between the incidences of human visceral
      leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the
      indicators and index of vulnerability. CONCLUSIONS: The environment in
      circumscribed areas helps as protection factor or increases the local
      vulnerability to the occurrence of human visceral leishmaniasis. The use of
      methodology that analyzes the conditions of life of the population and the
      spatial distribution of human visceral leishmaniasis is essential to identify the
      most vulnerable areas to the spread/maintenance of the disease. OBJETIVO:
      Analisar determinantes para a ocorrencia da leishmaniose visceral humana
      vinculados as condicoes de vulnerabilidade. METODOS: Estudo ecologico, cuja
      unidade de analise espacial foi a Unidade de Analise Territorial em Araguaina,
      TO, de 2007 a 2012. Foi realizada analise da situacao sociodemografica e de
      infraestrutura urbana no municipio. Indicadores primarios normalizados foram
      calculados e utilizados na construcao de indicadores de vulnerabilidade de
      estrutura social, de estrutura domiciliar e de infraestrutura urbana. A partir
      deles, foi composto um indice de vulnerabilidade. A estimativa de Kernel foi
      utilizada para avaliar a densidade de casos de leishmaniose visceral humana, com
      base nas coordenadas dos casos. O I-Moran Global Bivariado foi empregado para
      verificar a existencia de autocorrelacao espacial entre a incidencia de
      leishmaniose visceral humana e os indicadores e indice de vulnerabilidade. I
      Moran Local Bivariado foi utilizado para identificar clusters espaciais.
      RESULTADOS: Foi observado um padrao de disseminacao centrifuga da leishmaniose
      visceral humana no municipio, em que surtos da doenca atingiram progressivamente
      areas centrais e periurbanas. Houve correlacao entre maiores incidencias de
      leishmaniose visceral humana e piores condicoes de vida. Foram observados
      clusters estatisticamente significativos entre as incidencias de leishmaniose
      visceral humana nos dois periodos analisados (2007 a 2009 e 2010 a 2012) e os
      indicadores e indice de vulnerabilidade. CONCLUSOES: O ambiente em areas
      circunscritas contribui como fator de protecao ou aumenta a vulnerabilidade local
      a ocorrencia de leishmaniose visceral humana. O uso de metodologia que analisa as
      condicoes de vida da populacao e distribuicao espacial da leishmaniose visceral
      humana e essencial na identificacao de areas mais vulneraveis a
      disseminacao/manutencao da doenca.

PMID- 28513763
TI  - Interaction between demand-control and social support in the occurrence of common
      mental disorders.
AB  - OBJECTIVE: To analyze the interaction between the psychosocial aspects of work
      and the occurrence of common mental disorders among health workers. METHODS: This
      is a cross-sectional study conducted with a representative sample of workers of
      the primary health care of five municipalities of the State of Bahia, Brazil, in
      2012. The variable of outcome were the common mental disorders evaluated by the
      SRQ-20, and the variables of exposure were high demand (high psychological demand
      and low control over the work) and low social support in the workplace.
      Interaction was checked by the deviation of the additivity of the effects for the
      factors studied from the calculation of excess risk from interaction, proportion
      of cases attributed to interaction, and the synergy index. RESULTS: The global
      prevalence of common mental disorders was 21%. The group of combined exposure has
      shown higher magnitude (high demand and low social support), reaching 28% when
      compared to the 17% in the situation of no exposure (low demand and high social
      support). CONCLUSIONS: The results strengthen the hypothesis of interaction
      between the factors investigated, directing to the synergy of the effects.
      OBJETIVO: Analisar a interacao entre aspectos psicossociais do trabalho e a
      ocorrencia de transtornos mentais comuns entre trabalhadores da saude. METODOS:
      Estudo transversal conduzido em amostra representativa de trabalhadores da
      atencao basica de cinco municipios da Bahia em 2012. As variaveis desfecho foram
      os transtornos mentais comuns avaliados pelo SRQ-20, as de exposicao foram a alta
      exigencia (alta demanda psicologica e baixo controle sobre o proprio trabalho) e
      o baixo apoio social no trabalho. A interacao foi verificada pelo afastamento da
      aditividade dos efeitos para fatores estudados a partir do calculo do excesso de
      risco devido a interacao, proporcao de casos atribuida a interacao e indice de
      sinergia. RESULTADOS: A prevalencia global de transtornos mentais comuns foi de
      21%. Apresentou maior magnitude no grupo de exposicao combinada (alta exigencia e
      baixo apoio social), chegando a 28% quando comparada a 17% na situacao de nenhuma
      exposicao (baixa exigencia e alto apoio social). CONCLUSOES: Os resultados
      fortalecem a hipotese de interacao entre os fatores investigados, com direcao
      para a sinergia dos efeitos.

PMID- 28513765
TI  - Factors associated with suicidal ideation among university students.
AB  - Objective: to analyze the factors associated with suicidal ideation in a
      representative sample of university students. Methods: cross-sectional study,
      carried out with 637 students of the Federal University of Mato Grosso. The
      presence of suicidal ideation, demographic and socioeconomic variables, use of
      alcohol through the Alcohol, Smoking and Substance Involvement Screening Test,
      and depressive symptoms (Major Depression Inventory) were investigated. Bivariate
      analysis was performed with the Chi-square test and multivariate analysis using
      the Poisson regression model. Results: it was found that 9.9% of the students had
      suicidal thoughts in the previous 30 days and, in the bivariate analysis, the
      variables economic class, sexual orientation, religious practice, suicide
      attempts in the family and among friends, alcohol consumption and depressive
      symptoms were associated with suicidal ideation. In the multivariate analysis
      sexual orientation, suicide attempts in the family and the presence of depressive
      symptoms remained as associated factors. Conclusion: these findings constitute a
      situational diagnosis that enables the formulation of academic policies and
      preventive actions to confront this situation on the university campus.

PMID- 28513767
TI  - Capnography as a tool to detect metabolic changes in patients cared for in the
      emergency setting.
AB  - Objective:: to evaluate the usefulness of capnography for the detection of
      metabolic changes in spontaneous breathing patients, in the emergency and
      intensive care settings. Methods:: in-depth and structured bibliographical search
      in the databases EBSCOhost, Virtual Health Library, PubMed, Cochrane Library,
      among others, identifying studies that assessed the relationship between
      capnography values and the variables involved in blood acid-base balance.
      Results:: 19 studies were found, two were reviews and 17 were observational
      studies. In nine studies, capnography values were correlated with carbon dioxide
      (CO2), eight with bicarbonate (HCO3), three with lactate, and four with blood pH.
      Conclusions:: most studies have found a good correlation between capnography
      values and blood biomarkers, suggesting the usefulness of this parameter to
      detect patients at risk of severe metabolic change, in a fast, economical and
      accurate way. Objetivo:: avaliar a utilidade da capnografia para a deteccao de
      alteracoes metabolicas em pacientes com respiracao espontanea, no contexto das
      emergencias e dos cuidados intensivos. Metodo:: pesquisa bibliografica
      estruturada aprofundada, nas bases de dados EBSCOhost, Biblioteca Virtual em
      Saude, PubMed, Cochrane Library, entre outras, identificando estudos que
      avaliavam a relacao entre os valores da capnografia e as variaveis envolvidas no
      equilibrio acido-base sanguineo. Resultados:: foram levantados 19 estudos, dois
      eram revisoes e 17 eram estudos observacionais. Em nove estudos, os valores
      capnograficos foram correlacionados com o dioxido de carbono (CO2), em oito com o
      bicarbonato (HCO3), em tres com o lactato, e em quatro com o pH sanguineo.
      Conclusoes:: na maioria dos estudos foi observada uma correlacao adequada entre
      os valores capnograficos e os biomarcadores sanguineos, sugerindo a utilidade
      deste parametro para a identificacao de pacientes com risco de sofrer uma
      alteracao metabolica grave, de uma forma rapida, economica e precisa. Objetivo::
      explorar la utilidad de la capnografia para la deteccion de alteraciones
      metabolicas ante pacientes en respiracion espontanea, en el ambito de las
      emergencias y los cuidados criticos. Metodo:: busqueda bibliografica estructurada
      en profundidad, en bases de datos EBSCOhost, Biblioteca Virtual de la Salud,
      PubMed, Cochrane Library, entre otras, identificando estudios que evaluaban la
      relacion entre valores de la capnografia y variables implicadas en el equilibrio
      acido-base sanguineo. Resultados:: se recopilaron 19 estudios, dos eran
      revisiones y 17 observacionales. En nueve estudios, se correlacionaron los
      valores capnograficos junto al dioxido de carbono (CO2), en ocho con el
      bicarbonato (HCO3), tres con el lactato, y cuatro con el pH sanguineo.
      Conclusiones:: la mayoria de estudios han obtenido una correlacion adecuada entre
      los valores capnograficos y biomarcadores sanguineos, sugiriendo la utilidad de
      este parametro para la deteccion de pacientes en riesgo de padecer una alteracion
      metabolica grave, de forma rapida, economica y precisa.

PMID- 28513766
TI  - Intervening factors for the initiation of treatment of patients with stomach and
      colorectal cancer.
AB  - Objective: to identify the time between symptoms, the request for care and the
      beginning of treatment in patients with stomach and colorectal cancer as well as
      the factors that interfere in these processes. Method: correlational descriptive
      study, including 101 patients diagnosed with stomach or colorectal cancer,
      treated in a hospital specialized in oncology. Results: the 101 patients
      investigated there was predominance of males, mean age of 61.7 years. The search
      for medical care occurred within 30 days after the onset of symptoms, in most
      cases. The mean total time between the onset of symptoms and the beginning of
      treatment ranged from 15 to 16 months, and the mean time between the search for
      medical care and the diagnosis was 4.78 months. The family history of cancer
      (p=0.008) and the implementation of preventive follow-up (p<0.001) were
      associated with shorter periods between the search for care and the beginning of
      treatment. Nausea, vomiting, hematochezia, weight loss and pain were associated
      with faster demand for care. Conclusion: the longer interval between the search
      for medical care and the diagnosis was possibly due to the non-association
      between the presented symptoms and the disease.

PMID- 28513768
TI  - Microbiological testing of devices used in maintaining peripheral venous
      catheters.
AB  - Objective: to evaluate the use of peripheral venous catheters based on
      microbiological analysis of devices (dressing and three-way stopcocks) and thus
      contribute to the prevention and infection control. Methods: this was a
      prospective study of microbiological analysis of 30 three-way stopcocks (external
      surfaces and lumens) and 30 dressing used in maintaining the peripheral venous
      catheters of hospitalized adult patients. Results: all external surfaces, 40% of
      lumens, and 86.7% of dressing presented bacterial growth. The main species
      isolated in the lumen were 50% coagulase-negative Staphylococcus, 14.3%
      Staphylococcus aureus, and 14.3% Pseudomonas aeruginosa. Fifty nine percent of
      multidrug-resistant bacteria were isolated of the three-way stopcocks, 42% of the
      lumens, and 44% of the dressing with a predominance of coagulase-negative
      Staphylococcus resistant to methicillin. Besides, 18% gram-negative bacteria with
      resistance to carbapenems were identified from multidrug-resistant bacteria on
      the external surfaces of the three-way stopcocks. Conclusion: it is important to
      emphasize the isolation of coagulase-negative Staphylococcus and gram-negative
      bacteria resistant to methicillin and carbapenems in samples of devices,
      respectively, which reinforces the importance of nursing care in the maintenance
      of the biologically safe environment as well as prevention and infection control
      practices.

PMID- 28513769
TI  - The situation of nursing education in Latin America and the Caribbean towards
      universal health.
AB  - Objective:: to assess the situation of nursing education and to analyze the
      extent to which baccalaureate level nursing education programs in Latin America
      and the Caribbean are preparing graduates to contribute to the achievement of
      Universal Health. Method:: quantitative, descriptive/exploratory, cross-sectional
      study carried out in 25 countries. Results:: a total of 246 nursing schools
      participated in the study. Faculty with doctoral level degrees totaled 31.3%,
      without Brazil this is reduced to 8.3%. The ratio of clinical experiences in
      primary health care services to hospital-based services was 0.63, indicating that
      students receive more clinical experiences in hospital settings. The results
      suggested a need for improvement in internet access; information technology;
      accessibility for the disabled; program, faculty and student evaluation; and
      teaching/learning methods. Conclusion:: there is heterogeneity in nursing
      education in Latin America and the Caribbean. The nursing curricula generally
      includes the principles and values of Universal Health and primary health care,
      as well as those principles underpinning transformative education modalities such
      as critical and complex thinking development, problem-solving, evidence-based
      clinical decision-making, and lifelong learning. However, there is a need to
      promote a paradigm shift in nursing education to include more training in primary
      health care. Objetivo:: avaliar a situacao da educacao em enfermagem e analisar o
      quanto os programas de educacao em enfermagem, no nivel de Bacharelado na America
      Latina e no Caribe, estao preparando graduados a contribuir para o alcance da
      Saude Universal. Metodo:: estudo quantitativo, descritivo/exploratorio,
      transversal, realizado em 25 paises. Resultados:: um total de 246 escolas de
      enfermagem participaram do estudo. O corpo docente com nivel de Doutorado
      totalizou 31,3%; sem o Brasil o numero fica reduzido a 8,3%. A razao entre
      experiencias clinicas nos servicos de atencao primaria a saude e nos servicos
      hospitalares foi de 0,63, indicando que os estudantes tem mais experiencias
      clinicas nos cenarios hospitalares. Os resultados sugeriram necessidade de
      aprimoramento relacionada ao acesso a Internet; tecnologia da informacao; acesso
      para portadores de deficiencias; avaliacao do programa, do corpo docente e dos
      estudantes; e aos metodos de ensino/aprendizagem. Conclusao:: ha heterogeneidade
      na educacao em enfermagem na America Latina e no Caribe. Os curriculos de
      enfermagem incluem, geralmente, os principios e valores da Saude Universal e da
      atencao primaria a saude, bem como aqueles principios subjacentes as modalidades
      de educacao transformativa, como o desenvolvimento de pensamento critico e
      complexo, a solucao de problemas, a tomada de decisao clinica baseada em
      evidencias, e aprendizagem continua. No entanto, e preciso promover uma mudanca
      de paradigma na educacao em enfermagem que inclua mais treinamento na atencao
      primaria a saude. Objetivo:: evaluar la situacion de la educacion en enfermeria y
      analizar en que grado los programas de educacion de enfermeria a nivel de grado
      en America Latina y el Caribe estan preparando a los graduados para contribuir al
      logro de la Salud Universal. Metodo:: se llevo a cabo un estudio transversal,
      cuantitativo, descriptivo y exploratorio en 25 paises. Resultados:: participaron
      en el estudio 246 escuelas de enfermeria. El porcentaje de profesores con titulos
      de doctorado fue de 31,3%; pero, si se excluye a Brasil esta cifra se reduce a
      8,3%. La proporcion de la experiencia clinica adquirida en los servicios de
      atencion primaria de salud en relacion con la adquirida en servicios
      hospitalarios fue de 0,63, lo que indica que los estudiantes adquieren la mayor
      parte de su experiencia clinica en entornos hospitalarios. Los resultados
      mostraron una necesidad de mejorar el acceso a internet; la tecnologia de la
      informacion; la accesibilidad para las personas discapacitadas; la evaluacion de
      los programas, de los profesores y de los estudiantes; y los metodos de ensenanza
      y aprendizaje. Conclusiones:: hay heterogeneidad en la educacion en enfermeria en
      America Latina y el Caribe. En general, los programas de estudios de enfermeria
      han adoptado los principios y los valores de la Salud Universal y la atencion
      primaria de salud, asi como los principios que sustentan las modalidades de
      educacion transformadora, como son el desarrollo del pensamiento critico y
      complejo, la solucion de problemas, la toma de decisiones clinicas basadas en la
      evidencia y el aprendizaje a lo largo de toda la vida. Sin embargo, hay necesidad
      de promover un cambio en el paradigma de la educacion en enfermeria, a fin de que
      abarque mas capacitacion en la atencion primaria de salud.

PMID- 28513770
TI  - Association between MFN2 gene polymorphisms and the risk and prognosis of acute
      liver failure: a case-control study in a Chinese population.
AB  - This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms
      in the risk and prognosis of acute liver failure (ALF). A total of 298 blood
      samples were collected from 138 ALF patients (case group) and 160 healthy
      participants (control group). Coagulation function, glutamic pyruvic transaminase
      (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood
      ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2
      gene polymorphisms in the risk and prognosis of ALF patients was estimated using
      Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression
      analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood
      ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or
      the TT genotype of rs4846085 than in those with the CC genotype of these two
      SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk
      factor for ALF, respectively. Blood ammonia and LA levels were independent risk
      factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were
      protective factors for ALF. ALF patients with the GG genotype of rs873457 or the
      TT genotype of rs4846085 had a lower survival rate than those with other
      genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both
      independent factors affecting the prognosis of ALF patients. MFN2 gene
      polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be
      associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated
      with the risk and prognosis of ALF.

PMID- 28513772
TI  - Etanercept protects rat cardiomyocytes against hypertrophy by regulating
      inflammatory cytokines secretion and cell apoptosis.
AB  - We aimed to investigate the effect of etanercept, a tumor necrosis factor-alpha
      (TNF-alpha) inhibitor, on rat cardiomyocyte hypertrophy and its underlying
      mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley
      rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and
      then treated with different concentrations of etanercept (1, 10, and 50 MUM).
      After treatment, cell counts, viability and cell apoptosis were evaluated. The
      mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic
      factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT
      PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were
      measured by western blotting. The protein levels of transforming growth factor
      beta1 (TGF-beta1), interleukin (IL)-1beta, IL-6, leukemia inhibitory factor (LIF)
      and cardiotrophin-1 (CT-1) were determined using enzyme linked immunosorbent
      assay (ELISA) kits. In the present study, TNF-alpha level in cardiomyocytes with
      hypertrophy was significantly enhanced (P<0.05). Compared to the model group,
      cell number and viability were significantly increased and ratio of apoptotic
      cells was reduced by etanercept (P<0.05, P<0.01, or P<0.001). In addition,
      etanercept remarkably reduced the mRNA levels of ANF, MMP-9 and MMP-13, inhibited
      the expression of Bax, and increased the expression of Bcl-2 compared to the
      model group (P<0.05). ELISA results further showed that etanercept lowered the
      levels of IL-1beta, IL-6, LIF and CT-1 but not TGF-beta1 compared to the model
      group (P<0.05). Etanercept may protect rat cardiomyocytes from hypertrophy by
      inhibiting inflammatory cytokines secretion and cell apoptosis.

PMID- 28513771
TI  - Species distribution and antifungal susceptibility patterns of Candida isolates
      from a public tertiary teaching hospital in the Eastern Cape Province, South
      Africa.
AB  - Candida species are the leading cause of invasive fungal infections, and over the
      past decade there has been an increased isolation of drug resistant Candida
      species. This study aimed to identify the species distribution of Candida
      isolates and to determine their unique antifungal susceptibility and resistance
      patterns. During a cross-sectional study, 209 Candida isolates (recovered from
      206 clinical samples) were collected and their species distribution was
      determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa)
      was used to determine minimum inhibitory concentrations (MICs) to azoles
      (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes
      (amphotericin B) and flucytosine. Four species of Candida were isolated, of which
      C. albicans was the most frequent, isolated in 45.4% (95/209) of the isolates,
      followed by C. glabrata: 31.1% (65/209). The MICs of the different antifungal
      drugs varied amongst the species of Candida. From the 130 isolates tested for
      MICs, 90.77% (112/130) were susceptible to all antifungal drugs and 6.9% (9/130)
      of the isolates were multi-drug resistant. C. dubliniensis (n=2) isolates were
      susceptible to all the above mentioned antifungal drugs. There was no significant
      difference in species distribution amongst clinical specimens and between
      patients' genders (P>0.05). An increase in MIC values for fluconazole and
      flucytosine towards the resistance range was observed. To our knowledge, this is
      the first report on surveillance of Candida species distribution and antifungal
      susceptibility at a public tertiary teaching hospital in Eastern Cape, South
      Africa.

PMID- 28513773
TI  - Attenuation of renal ischemic reperfusion injury by salvianolic acid B via
      suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway.
AB  - Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia
      miltiorrhiza and exhibit numerous health promoting properties. The objective of
      the current study was to examine whether SAB exerts a renoprotective effect by
      attenuating oxidative stress and inflammatory response through activating
      phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling
      pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats
      (250-300 g) were obtained and split into four groups with ten rats in each group.
      The right kidney of all rats was removed (nephrectomy). The rats of the Control
      group received only saline (occlusion) and served as a sham control group,
      whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left
      renal artery served as a postitive control group. The other 2 groups of rats were
      pretreated with SAB (20 and 40 mg.kg-1.day-1) for 7 days prior IR induction and
      served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr)
      and blood urea nitrogen (BUN) were significantly lower in the groups that
      received SAB. Pretreatment with SAB appears to attenuate oxidative stress by
      suppressing the production of lipid peroxidation products like malondialdehyde as
      well as elevating antioxidant activity. The concentration of inflammatory markers
      and neutrophil infiltration (myeloperoxidase) were significantly decreased.
      Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly
      upregulated upon supplementation with SAB, indicating its renoprotective
      activity. Taken together, these results indicate that SAB can therapeutically
      alleviate oxidative stress and inflammatory process via modulating PI3K/Akt
      signaling pathway and probably ameliorate renal function and thus act as a
      renoprotective agent.

PMID- 28513774
TI  - Hippocampal overexpression of Down syndrome cell adhesion molecule in amyloid
      precursor protein transgenic mice.
AB  - Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome
      critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental
      protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We
      previously demonstrated DSCAM overexpression in the cortex of amyloid precursor
      protein (APP) transgenic mice, suggesting possible regulatory interactions
      between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent
      learning and memory. In this preliminary study, we examined age-related changes
      in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and
      12 months old). Hippocampus-dependent spatial memory was assessed in APP mice and
      age-matched wild type littermates (WTs) using the Morris water maze (MWM). The
      cellular distribution of hippocampal DSCAM and total expression at both mRNA and
      protein levels were measured by immunohistochemistry, qRT-PCR, and western
      blotting, respectively. APP mice exhibited spatial memory deficits in the MWM.
      Intense DSCAM immunoreactivity was observed in the dentate gyrus granule cell
      layer and hippocampal stratum pyramidale. Total hippocampal DSCAM mRNA and
      protein expression levels were substantially higher in APP mice than WTs at 1 and
      3 months of age. Expression decreased with age in both groups but remained higher
      in APP mice. DSCAM is overexpressed in the hippocampus over the first 12 months
      of life in APP mice, but especially during maturation to adulthood. In
      conclusion, these results suggest an association between DSCAM and APP mice,
      which is characterized by neuropathology and behavioral deficits. These results
      provide some clues for future studies on the role of DSCAM overexpression in the
      precocious cognitive decline observed in APP transgenic mice.

PMID- 28513776
TI  - CHARACTERIZATION AND INFLUENCE OF SUBTROPICAL PERSIMMON CULTIVARS ON JUICE AND
      JELLY CHARACTERISTICS.
AB  - To increase the availability to consumers and add more value to persimmon
      (Diospyros kaki L.), which is a very perishable and seasonal fruit and in order
      to identify which cultivars grown in subtropical regions are more suitable for
      processing in the form of juice and jelly, as well as understand what the
      consumer profile is for these products, the objective of this study was to
      evaluate the influence of different persimmon cultivars (Rama Forte, Mel, Guiombo
      and Taubate) grown in subtropical regions of Brazil on the physicochemical
      characteristics, rheological properties and sensory acceptance of the resulting
      juice and jelly in order to identify cultivars with the greatest potential for
      industrial use. The different studied persimmon cultivars had different physical
      and physicochemical characteristics which resulted in juices and jellies with
      different physicochemical, rheological and sensory characteristics. Based on
      sensory acceptance and productivity/adaptability of persimmon crop in Brazil, the
      most suitable persimmon cultivars for processing are Rama Forte and Guiombo. In
      this study it was found that the consumer prefers a more acidic persimmon juice
      and a less firm or softer, less sweet, clearer and more intense yellow color
      persimmon jelly.

PMID- 28513775
TI  - Adiponectin inhibits oxidization-induced differentiation of T helper cells
      through inhibiting costimulatory CD40 and CD80.
AB  - Adiponectin is a multifunctional adipokine that has several oligomeric forms in
      the blood stream, which broadly regulates innate and acquired immunity.
      Therefore, in this study, we aimed to observe the differentiation of T helper
      (Th) cells and expression of costimulatory signaling molecules affected by
      adiponectin. The mRNA and protein expression levels of adiponectin and its
      receptors in oxidized low density lipoprotein cholesterol-treated endothelial
      cells were assayed by real time PCR and immunofluorescence. The endothelial cells
      were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and
      co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets
      were assayed by flow cytometry. The effects of adiponectin on costimulatory
      signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow
      cytometry. The results showed that endothelial cells expressed adiponectin and
      its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1
      and Th17 differentiation through adipoR1 receptor, contributed to the inhibition
      of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting
      antigen presenting action.

PMID- 28513777
TI  - Population dynamics of Siderastrea stellata Verrill, 1868 from Rocas Atoll, RN:
      implications for predicted climate change impacts at the only South Atlantic
      atoll.
AB  - Coral reefs are one of the most vulnerable ecosystems to ocean warming and
      acidification, and it is important to determine the role of reef building species
      in this environment in order to obtain insight into their susceptibility to
      expected impacts of global changes. Aspects of the life history of a coral
      population, such as reproduction, growth and size-frequency can contribute to the
      production of models that are used to estimate impacts and potential recovery of
      the population, acting as a powerful tool for the conservation and management of
      those ecosystems. Here, we present the first evidence of Siderastrea stellata
      planulation, its early growth, population size-frequency distribution and growth
      rate of adult colonies in Rocas Atoll. Our results, together with the
      environmental protection policies and the absence of anthropogenic pressures,
      suggest that S. stellata population may have a good potential in the maintenance
      and recovery in the atoll. However, our results also indicate an impact on
      corals' recruitment, probably as a consequence of the positive temperature
      anomaly that occurred in 2010. Thus, despite the pristine status of Rocas Atoll,
      the preservation of its coral community seems to be threatened by current global
      changes, such as more frequent thermal stress events.

PMID- 28513779
TI  - The preventive effects of ascorbic acid supplementation on locomotor and
      acetylcholinesterase activity in an animal model of schizophrenia induced by
      ketamine.
AB  - Studies have shown that schizophrenic patients seem to have nutritional
      deficiencies. Ascorbic acid (AA) has an important antioxidant effect and
      neuromodulatory properties. The aim of this study was to evaluate the effects of
      AA on locomotor activity and the acetylcholinesterase activity (AChE) in an
      animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10
      mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals
      received Ketamine (Ket) (25 mg/kg) or saline (i.p). After the last administration
      (30 min) rats were subjected to the behavioral test. Brain structures were
      dissected for biochemical analysis. There was a significant increase in the
      locomotor activity in Ket treated. AA prevented the hyperlocomotion induced by
      ket. Ket also showed an increase of AChE activity within the prefrontal cortex
      and striatum prevented by AA. Our data indicates an effect for AA in preventing
      alterations induced by Ket in an animal model of SZ, suggesting that it may be an
      adjuvant approach for the development of new therapeutic strategies within this
      psychiatric disorder.

PMID- 28513780
TI  - Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential
      of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by
      Ethanol.
AB  - Hepatic disorders such as steatosis and alcoholic steatohepatitis are common
      diseases that affect thousands of people around the globe. This study aims to
      identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to
      evaluate some oxidative stress parameters and the hepatoprotective action of
      green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of
      rats treated with ethanol. The results showed five polyphenols in the lyophilized
      coconut water spiked with standards: chlorogenic acid (0.18 uM), caffeic acid
      (1.1 uM), methyl caffeate (0.03 uM), quercetin (0.08 uM) and ferulic acid (0.02
      uM) isomers. In the animals, the activity of the serum gamma
      glutamyltranspeptidase (gamma-GT) was reduced to 1.8 I.U/L in the coconut water
      group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid
      groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver,
      the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol
      group of 36.2% and 48.0% for pretreated and post treated coconut water group
      respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid
      group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid
      reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol
      group. These data indicate that the green dwarf coconut water, caffeic and
      ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage
      properties, thus decreasing the oxidative stress induced by ethanol metabolism.

PMID- 28513781
TI  - Mitochondria-rich cells changes induced by nitrite exposure in tambaqui
      (Colossoma macropomum Cuvier, 1818).
AB  - The gill mitochondria-rich cells of the juvenile Amazonian fish Colossoma
      macropomum were analyzed using light and scanning and transmission electron
      microscopy after 96 h exposure to 0.04 and 0.2 mM nitrite. Although the number of
      mitochondria-rich cells decreased significantly in the lamellar epithelium, no
      decrease was found in the interlamellar region of the gill filament. Nitrite
      exposure caused significant reduction on the apical surface area of individual
      mitochondria-rich cells (p < 0.05), with a resulting reduction of the fractional
      area of these cells in both the lamellar and filament epithelium. Swelling of
      endoplasmic reticulum cisternae, nuclear envelope and mitochondria were the main
      changes found in the mitochondria-rich cells. Cristae lysis and matrix
      vacuolization characterized the mitochondrial changes. The overall
      ultrastructural changes indicated cellular functional disruption caused by
      exposure to nitrite. The changes observed in the gill indicate that the cellular
      structures involved in the process of energy production become severely damaged
      by exposure to nitrite indicating irreversible damage conducting to cell death.

PMID- 28513782
TI  - Soil-vegetation relationships and community structure in a "terra-firme"-white
      sand vegetation gradient in Virua National Park, northern Amazon, Brazil.
AB  - Virua National Park encompasses a vast and complex system of hydromorphic sandy
      soils covered largely by the white sand vegetation ("Campinarana") ecosystem. The
      purpose of this study was to investigate a vegetation gradient of "terra-firme"
      white sand vegetation at the Virua National Park. Nine plots representing three
      physiognomic units were installed for floristic and phytosociological surveys as
      well as to collect composite soil samples. The data were subjected to assessments
      of floristic diversity and similarity, phytosociological parameters and to
      statistical analyses, focused on principal components (PC) and canonical
      correspondence analysis (CCA). The vegetation of the Campinaranas types and
      Forest differed in biomass and species density. Ten species, endemic to Brazil,
      were particularly well-represented. PC and CCA indicated a clear distinction
      between the studied plots, based on measured soil variables, especially base sum
      and clay, which were the most differentiating properties between Campinarana and
      Forest; For the separation of the Campinarana types, the main distinguishing
      variable was organic matter content and cation exchange capacity. Higher
      similarity of Campinaranas was associated to a monodominant species and the lower
      similarity of Forest was related to the high occurrence of locally rare species.

PMID- 28513784
TI  - Chlorhexidine with or without alcohol against biofilm formation: efficacy,
      adverse events and taste preference.
AB  - In recent years, different chlorhexidine formulations have been tested, including
      an alcohol-free alternative, but the effect of this solution on early biofilm
      formation is not clear. A crossover, randomized, double-blind clinical trial was
      conducted to evaluate the effect of two chlorhexidine solutions against supra-
      and subgingival biofilm formation (NCT#02656251). Thirty-five participants were
      randomized and asked to rinse twice daily with 15 ml of an alcohol-containing
      0.12% chlorhexidine solution, an alcohol-free 0.12% chlorhexidine solution, or
      placebo. The study was conducted in three experimental periods of 4 days each,
      with a 10-day washout between the periods. All the experimental periods followed
      the same protocol, except that the solutions were switched. Biofilm distribution
      was evaluated every 24 hours by the Plaque-Free Zone Index, during 96 hours.
      Adverse events were self-reported and sensory evaluation was performed using a
      hedonic scale. Compared to the placebo, the chlorhexidine solutions resulted in a
      significantly higher number of surfaces free of plaque over 96 hours (p < 0.01),
      and were able to prevent subgingival biofilm formation (p < 0.01). The alcohol
      free chlorhexidine solution was associated with a lower incidence of adverse
      events, compared with alcohol-containing chlorhexidine (p < 0.05); it also
      received better sensory evaluation and acceptance by trial participants, compared
      with the alcohol-containing chlorhexidine (p = 0.007), and had a similar
      inhibitory effect on the formation of supra- and subgingival biofilms.

PMID- 28513783
TI  - Influence of addition of [2-(methacryloyloxy)ethyl]trimethylammonium chloride to
      an experimental adhesive.
AB  - The aim of this study was to develop an experimental adhesive with addition of [2
      (methacryloyloxy)ethyl]trimethylammonium chloride (METAC) and to evaluate its
      mechanical and biological properties and its in vitro antibacterial activity. An
      experimental adhesive resin was formulated with Bis-GMA, TEGDMA, and HEMA. The
      antibacterial monomer was added at concentrations of 1%, 2.5%, and 5% (METAC
      groups). A group without METAC addition was used as control. The experimental
      adhesives were evaluated as to their antibacterial potential against
      Streptococcus mutans, degree of conversion, and softening in ethanol for 2 hours.
      The data were analyzed by one-way ANOVA, Tukey's post-hoc test, and the paired
      Student's t-test (significance level of 0.05). METAC showed antibacterial
      activity against S. mutans at all concentrations (p < 0.05). There was no
      statistical difference across METAC groups (p > 0.05). The 1%, 2.5%, and 5%
      groups yielded the highest mean values for degree of conversion (p < 0.05). The
      1% group did not differ from the control group (p > 0.05). There was no
      statistical difference in baseline microhardness values (p > 0.05) and
      microhardness values after immersion in ethanol were lower than at baseline for
      all groups (p < 0.05). There was no statistical difference in the reduction of
      Knoop hardness number (KHN) after immersion in ethanol for any of the groups (p >
      0.05). The results of the present study indicate that METAC is a promising
      antibacterial agent when added to an adhesive system.

PMID- 28513785
TI  - Microbiological outcomes from different periodontal maintenance interventions: a
      systematic review.
AB  - This study aimed to investigate the differences in the subgingival
      microbiological outcomes between periodontal patients submitted to a
      supragingival control (SPG) regimen as compared to subgingival scaling and root
      planing performed combined with supragingival debridement (SPG + SBG)
      intervention during the periodontal maintenance period (PMP). A systematic
      literature search using electronic databases (MEDLINE and EMBASE) was conducted
      looking for articles published up to August 2016 and independent of language. Two
      independent reviewers performed the study selection, quality assessment and data
      collection. Only human randomized or non-randomized clinical trials with at least
      6-months-follow-up after periodontal treatment and presenting subgingival
      microbiological outcomes related to SPG and/or SPG+SBG therapies were included.
      Search strategy found 2,250 titles. Among these, 148 (after title analysis) and
      39 (after abstract analysis) papers were considered to be relevant. Finally, 19
      studies were selected after full-text analysis. No article had a direct
      comparison between the therapies. Five SPG and 14 SPG+SBG studies presented
      experimental groups with these respective regimens and were descriptively
      analyzed while most of the results were only presented graphically. The results
      showed that both SPG and SPG+SBG protocols of PMP determined stability in the
      microbiological results along time. Nevertheless, new studies comparing these
      interventions in PMP are needed, especially if the limitations herein discussed
      could be better controlled.

PMID- 28513787
TI  - Does the trait anxiety affect the dental fear?
AB  - The aims of the present study were to evaluate possible associations between
      trait anxiety, dental fear and the predictors of these interactions including
      demographic characteristics and dental history of patients applied to the dental
      care center in Ankara, Turkey. A sample of 607 participants (mean age: 21.02 +/-
      2.32) responded to a Turkish version of the Modified Dental Fear Survey (MDFS),
      the State-Trait Anxiety Inventory (STAI-T) and a questionnaire regarding previous
      negative dental experience. Multiple logistic regression analysis was used to
      identify the association between dental fear and the independent variables
      including trait anxiety, age groups, education level, dental visit frequency,
      experience and the source of dental knowledge. There was a trend for increasing
      in trait anxiety scores with greater levels of dental fear in a medium level of
      the dental fear group (OR = 1.055, 95%CI [1.025-1.086]; p < 0.001) and in a high
      level of the dental fear group (OR = 1.090 [1.057-1.124]; p < 0.001). Comparing
      to the low level of dental fear group; participants of medium dental fear level
      intended more likely to go to the dentist when they have a complaint instead of
      regularly going (odds ratio; OR = 3.177, 95%CI [1.304-7.741]; p = 0.011).
      Participants of high dental fear level tended to be less likely to have
      experienced no problem (OR = 0.476, 95%CI [0.284-0.795]; p = 0.005) than the low
      level of the dental fear group. We strongly indicate that higher dental fear
      scores have a predisposition of having high trait anxiety scores. Unpleasant
      dental experiences increased the risk for high dental fear levels. Patients with
      dental fear tended only to visit a dentist when necessary, avoiding regular
      visits.

PMID- 28513786
TI  - 3-year survival rates of retained composite resin and ART sealants using two
      assessment criteria.
AB  - The aim was to test the null-hypothesis that there is no difference in the
      cumulative survival rate of retained composite resin (CR) sealants and a high
      viscosity glass-ionomer Atraumatic Restorative Treatment (ART) sealant in first
      permanent molars calculated according to the traditional and the modified
      retention assessment criteria over a period of 3 years. This cluster-randomized
      controlled clinical trial consisted of 123 schoolchildren, 6-7-years-old. At
      baseline, high-caries risk pits and fissures of fully erupted first permanent
      molars were treated with CR and ART sealants. Evaluations were performed after
      0.5, 1, 2 and 3 years. Retention was scored for free-smooth surface and for each
      of three sections into which the occlusal surface had been divided. The modified
      criterion differed from the traditional in that it determined an occlusal sealant
      to be a failure when at least one section contained no visible sealant material.
      Data were analysed according to the PHREG model with frailty correction, Wald
      test, ANOVA and t-test, using the Jackknife procedure. The cumulative survival
      rates for retained CR and ART sealants in free-smooth and occlusal surfaces for
      both criteria were not statistically significantly different over the 3 years. A
      higher percentage of retained CR sealants on occlusal surfaces was observed at
      longer evaluations. Cumulative survival rates were statistically significantly
      lower for the modified criterion in comparison to the traditional. The modified
      retention assessment criterion should be used in future sealant-retention
      studies.

PMID- 28513788
TI  - Comparisons of IgA response in saliva and colostrum against oral streptococci
      species.
AB  - The present study compared IgA specificity against oral streptococci in colostrum
      and saliva samples. Sixty-two mother-and-child pairs were included; samples of
      colostrum (C) and saliva (MS) were collected from the mothers and saliva samples
      were collected from babies (BS). The specificity of IgA against Streptococcus
      mutans and S. mitis were analyzed by western blot. Only 30% of babies' samples
      presented IgA reactivity to S. mutans, while 74 and 80% of MS and C,
      respectively, presented this response. IgA reactivity to S. mutans virulence
      antigens (Ag I/II, Gtf and GbpB) in positive samples showed differences between
      samples for Gtf and especially for GbpB (p < 0.05), but responses to Ag I/II were
      similar (p > 0.05). The positive response of Gtf-reactive IgA was different
      between C (90%) and MS (58%) samples (p < 0.05), but did not differ from BS (p >
      0.05). GbpB was the least detected, with 48 and 26% of C and MS, and only 5% of
      BS samples presenting reactivity (p > 0.05). Eight percent of MS and C samples
      presented identical bands to SM in the same time-point. In conclusion, the
      differences of IgA response found between C and MS can be due to the different
      ways of stimulation, proliferation and transportation of IgA in those secretions.
      The colostrum has high levels of IgA against S. mutans virulence antigens, which
      could affect the installation and accumulation process of S. mutans, mainly by
      supplying anti-GbpB IgA to the neonate.

PMID- 28513789
TI  - Effect of final irrigation protocols on microhardness reduction and erosion of
      root canal dentin.
AB  - This study aimed to evaluate the effect of final irrigation protocols on
      microhardness reduction and erosion of root canal dentin. Sixty root canals from
      mandibular incisors were instrumented and randomly divided into six groups (n =
      10) according to the irrigant used: QMiX, 17% EDTA, 10% citric acid (CA), 1%
      peracetic acid (PA), 2.5% NaOCl (solution control), and distilled water (negative
      control). The chelating solutions were used to irrigate the canal followed by
      2.5% NaOCl as a final flush. After the irrigation protocols, all specimens were
      rinsed with 10 mL of distilled water to remove any residue of the chemical
      solutions. Before and after the final irrigation protocols, dentin microhardness
      was measured with a Knoop indenter. Three indentations were made at 100 um and
      500 um from the root canal lumen. Afterwards, the specimens were prepared for
      scanning electron microscopic analysis and the amount of dentin erosion was
      examined. Wilcoxon and Kruskal-Wallis tests were used to analyze the results with
      a significance level set at 5%. At 100 um, all protocols significantly reduced
      dentin microhardness (p < .05), while at 500 um, this effect was detected only in
      the EDTA and QMiX groups (p < .05). CA was the irrigant that caused more
      extensive erosion in dentinal tubules, followed by PA and EDTA. QMiX opened
      dentinal tubules, but did not cause dentin erosion. Results suggest that QMiX and
      17% EDTA reduced dentin microhardness at a greater depth. Additionally, QMiX did
      not cause dentin erosion.

PMID- 28513791
TI  - The prevalence of diabetes mellitus and its associated factors in the Brazilian
      adult population: evidence from a population-based survey.
AB  - Objective:: To estimate the prevalence of self-reported diabetes mellitus (DM)
      and its associated factors among the Brazilian adult population. Methods:: The
      prevalence of DM was assessed in the Survey on Social Dimensions of Inequalities,
      a national survey with macro-regions representativeness carried out in 2008. Data
      were collected by a personal face-to-face interview with 12,423 individuals of
      both sexes, aged over 20 years. The chi2 test at 5.0% was performed in order to
      identify associated factors, and logistic regression was used to estimate
      adjusted odds ratios. Results:: The prevalence of DM in Brazil was 7.5%. After
      adjusting for potential confounders, diabetes remained associated with age (>= 40
      years), education (< 8 years of study), marital status (non-married), obesity,
      sedentary lifestyle, comorbidity with hypertension and hypercholesterolemia, as
      well as the demand for health services. Conclusion:: Results indicate a high
      prevalence of DM and its associated preventable factors in Brazil. Thus, they
      highlight the need for a behavioral change as a strategy for prevention and
      control of diabetes and its complications.

PMID- 28513790
TI  - [Sanitation and racial inequality conditions in urban Brazil: an analysis focused
      on the indigenous population based on the 2010 Population Census].
AB  - Objective:: The aims of this study were to analyze and describe the presence and
      infrastructure of basic sanitation in the urban areas of Brazil, contrasting
      indigenous with non-indigenous households. Methods: A cross-sectional study based
      on microdata from the 2010 Census was conducted. The analyses were based on
      descriptive statistics (prevalence) and the construction of multiple logistic
      regression models (adjusted by socioeconomic and demographic covariates). The
      odds ratios were estimated for the association between the explanatory variables
      (covariates) and the outcome variables (water supply, sewage, garbage collection,
      and adequate sanitation). The statistical significance level established was 5%.
      Results:: Among the analyzed services, sewage proved to be the most precarious.
      Regarding race or color, indigenous households presented the lowest rate of
      sanitary infrastructure in Urban Brazil. The adjusted regression showed that, in
      general, indigenous households were at a disadvantage when compared to other
      categories of race or color, especially in terms of the presence of garbage
      collection services. These inequalities were much more pronounced in the South
      and Southeastern regions. Conclusion:: The analyses of this study not only
      confirm the profile of poor conditions and infrastructure of the basic sanitation
      of indigenous households in urban areas, but also demonstrate the persistence of
      inequalities associated with race or color in the country.

PMID- 28513792
TI  - Evaluation of the Brazilian population's intake of antioxidant nutrients and
      their relation with the nutritional status.
AB  - Introduction:: The study of dietary antioxidants has gained prominence owing to
      the elucidation of the deleterious effects of oxidative stress to the human body.
      Objective: To evaluate the Brazilian population's intake of antioxidant nutrients
      and their association with the nutritional status. Methods:: A cross-sectional
      study was carried out including secondary data on food consumption of 33,459
      individuals from both sexes, aged 10 years or older, from all Brazilian regions
      based on microdata of the "2008-2009 Household Budget Survey, Brazilian Dairy
      Survey." The content of vitamins E, A, and C; zinc; manganese; copper; and
      selenium from 188 food items, divided into 12 groups, according to the habitual
      consumption form was analyzed. The means of antioxidant nutrient intake according
      to the nutritional status were compared using Bonferroni's t-test. Results::
      Higher percentages of insufficient intake of vitamins than antioxidant minerals
      were seen. A significant difference in the intake of vitamin E as to the
      nutritional status was noticed, wherein the intake in overweight individuals was
      lower than in those with proper weight. Participants with low weight presented
      lower intake of almost all antioxidant minerals, except for copper, in which the
      intake of participants with low weight was equal to those with normal weight.
      Conclusion:: High percentages of insufficient intake of antioxidant nutrients
      were observed in the studied population, especially vitamins. It was also found
      that the intake of antioxidant nutrients varied based on nutritional status,
      gender, and life stage.

PMID- 28513793
TI  - Social inequalities in the prevalence of common mental disorders in adults: a
      population-based study in Southern Brazil.
AB  - Objective:: This study aimed to investigate the prevalence and factors associated
      with Common Mental Disorders (CMD) in adults in a capital city in Southern
      Brazil. Methods:: Population-based survey conducted on 1,720 adults aged 20 - 59
      years from Florianopolis, Southern Brazil. The CMD were investigated through the
      Self-Reporting Questionnaire (SRQ-20). The independent variables were
      demographic, socioeconomic, health-related behaviors, health conditions and use
      of health services. Multivariable Poisson regression was used for the estimation
      of prevalence ratios (PR) and 95%CI. Results:: The prevalence of CMD was 14.7%.
      Adjusted analyses showed that the prevalence was higher among women, those self
      reported as blacks, with lower educational level, poor,
      divorced/separated/widowed, inactive in leisure time, heavy smokers, people with
      chronic diseases, those who reported negative health self-rating, those who had
      medical appointments and who were hospitalized before the interview. Conclusion::
      CMD is relatively high among population subgroups most vulnerable to social
      inequalities and with worse conditions related to health indicators.

PMID- 28513794
TI  - Psychotropic drug use among older adults: prevalence and associated factors.
AB  - Objective:: Investigating the prevalence of psychotropic drug use among older
      adults and factors associated with it. Methods:: This study was based on the Belo
      Horizonte Metropolitan Area Health Survey, conducted in 2003. It involved 1,635
      elderly (60 years or older) citizens, who were residents of cities within the
      Belo Horizonte Metropolitan Area and were selected using complex randomize
      sampling. Logistic regression models were used to identify factors associated
      with psychotropic drug use, with a 5.0% significance level. Results:: The
      prevalence of psychotropic drug use in the sample was 13.4%; specifically, 8.3%
      of individuals surveyed used benzodiazepines, whereas 5.0% used antidepressants.
      The following factors were independently associated with the use of psychotropic
      drugs: female gender (OR = 2.20; 95%CI 1.49 - 3.27), medical diagnosis of
      depression (OR = 6.42; 95%CI 4.31 - 9.55), 5 or more medical appointments in the
      last 12 months (OR = 2.15; 95%CI 1.32 - 3.53), and subscription to private health
      insurance (OR = 2.69; 95%CI 1.86 - 3.88). Conclusion:: The prevalence observed
      was similar to the one verified in other elderly Brazilian populations and the
      pattern of associated factors was consistent with the one detected for older
      populations of higher-income countries. Medical diagnosis of depression was the
      factor most strongly associated with psychotropic drug use.

PMID- 28513795
TI  - Balance of macronutrient intake among Brazilian elderly: analysis of the National
      Dietary Survey 2008-2009.
AB  - Objective:: This study aimed at evaluating the balance in the intake of protein,
      carbohydrate, and fat among the Brazilian elderly population. Methods:: The data
      analyzed were taken from the National Dietary Survey 2008-2009, from a total of
      4,286 Brazilian elders (60-104 years old). Based on the dietary intake obtained
      from two food records, the Multiple Source Method (MSM) was used to evaluate the
      macronutrients and saturated fat. The AMDR (Acceptable Macronutrient Distribution
      Range), by the Institute of Medicine (IOM), was used to evaluate the
      macronutrient energy percentage (%E). Linear regression models identified
      differences between macronutrients %E and household location (urban or rural),
      Brazilian macro-regions and gender. Results:: Protein intake showed higher
      agreement with the AMDR reference value (99.86%). It was observed that in 9.2% of
      the population, fat intake was higher than the reference value, almost twice as
      high as the carbohydrate-energy percentage (4.9%) and nine times higher than
      protein (1.0%). Among those with low carbohydrate-energy percentage, 14.5% had
      higher fat-energy percentage (beta = 8.19; p < 0.001), which means that 50% of
      the elderly whose carbohydrate intake was above the recommendation presented an
      overconsumption of fat. According to the macro-regions, the Midwest region was
      the only one to show differences for carbohydrate-energy percentage, which was
      lower than the others regions (51.6%; p < 0.05). The South region presented the
      lowest protein-energy percentage (17.9%; p < 0.01) and the highest fat-energy
      percentage (28.7%; p < 0.01). Conclusion:: Higher prevalence of inadequate fat
      intake among the Brazilian elderly may indicate an important public health
      problem that is associated with an increased risk of chronic diseases.

PMID- 28513796
TI  - Adequacy of sphygmomanometer cuff to brachial circumference of people attended in
      Primary Health Care Centers.
AB  - Objective:: To evaluate the adequacy of sphygmomanometer cuff to brachial
      circumference (BC) of individuals treated at Primary Health Care Centers.
      Methods:: Epidemiological, observational, and quantitative cross-sectional study.
      A total of 381 blood pressure (BP) readings conducted by nursing professionals
      were observed at 18 service units selected by drawing, considering two modalities
      of care centers. The correct use of the cuff was the main outcome variable. The
      BC was measured using inelastic measuring tape. The tests used for statistical
      analysis were Student's t-test, chi2, or Fisher's exact test. Results:: The
      measurement of BC ranged from 19.5 to 45.0 cm (mean = 30.4; standard deviation -
      SD = 4.3). Among the BP measurements, 218 (57.2%) of them were conducted with the
      appropriately sized cuff, being more frequent in the units with Family Health
      Teams (59.6 versus 40.4; p < 0.001). Ninety-three (24.2%) BC measurements were <
      27 cm and 63 (16.5%) were > 34 cm. The adult cuff was used correctly 209 (59.4%)
      times and the large adult cuff was used correctly 9 (31.0%) times. Conclusion::
      The study found an inadequacy in the use of the cuff in 42.8% of blood pressure
      readings in the Primary Health Care Centers. Similar studies should be performed
      in other cities and areas to estimate the effect of this problem in the diagnosis
      and monitoring of systemic arterial hypertension (SAH).

PMID- 28513797
TI  - Oral health self-perception in quilombola communities in Rio Grande do Sul: a
      cross-sectional exploratory study.
AB  - Objective:: There's a shortage of evidence on the oral health of quilombolas.
      This study aims to describe oral health self-perception, as well as to verify its
      associated factors in quilombola communities in the state of Rio Grande do Sul.
      Methods:: The data for this cross-sectional health survey were collected by
      application of a questionnaire. Since this study was part of a survey on
      nutritional security, the probabilistic cluster sample was estimated for the
      outcome of nutritional insecurity, comprising 583 individuals across quilombola
      communities in Rio Grande do Sul. The association between the outcome of negative
      oral health self-perception and sociodemographic, general health, and oral health
      variables was measured by prevalence ratios obtained through Poisson regressions
      with robust variance and 95% confidence intervals. Results: : Negative self-rated
      oral health was reported by 313 (53.1%) of the individuals. Satisfaction with
      chewing ability and satisfaction with oral appearance were associated with a
      higher prevalence of negative perception of oral health, while there was no
      association between the outcome and number of teeth. Use of alcohol had a
      borderline association with the outcome. Conclusion:: Satisfaction with
      appearance and chewing ability are factors associated with oral-health self
      perception of the quilombolas in Rio Grande do Sul.

PMID- 28513798
TI  - Anemia and hemoglobin levels among Indigenous Xavante children, Central Brazil.
AB  - Objective:: To evaluate the prevalence of anemia, mean hemoglobin levels, and the
      main nutritional, demographic, and socioeconomic factors among Xavante children
      in Mato Grosso State, Brazil. Methods:: A survey was conducted with children
      under 10 years of age in two indigenous Xavante communities within the Pimentel
      Barbosa Indigenous Reserve. Hemoglobin concentration levels, anthropometric
      measurements, and socioeconomic/demographic data were collected by means of
      clinical measurements and structured interviews. The cut-off points recommended
      by the World Health Organization were used for anemia classification. Linear
      regression analyses with hemoglobin as the outcome and Poisson regression with
      robust variance and with the presence or absence of anemia as outcomes were
      performed (95%CI). Results:: Lower mean hemoglobin values were observed in
      children under 2 years of age, without a significant difference between sexes.
      Anemia was observed among 50.8% of children overall, with the highest prevalence
      among children under 2 years of age (77.8%). Age of the child was inversely
      associated with the occurrence of anemia (adjusted PR = 0.60; 95%CI 0.38-0.95)
      and mean hemoglobin values increased significantly with age. Greater height-for
      age z-score values reduced the probability of having anemia by 1.8 times
      (adjusted PR = 0.59; 95%CI 0.34-1.00). Presence of another child with anemia
      within the household increased the probability of the occurrence of anemia by
      52.9% (adjusted PR = 1.89; 95%CI 1.16-3.09). Conclusion:: Elevated levels of
      anemia among Xavante children reveal a disparity between this Indigenous
      population and the national Brazilian population. Results suggest that anemia is
      determined by complex and variable relationships between socioeconomic,
      sociodemographic, and biological factors.

PMID- 28513799
TI  - Energy and nutrient intake according to away-from-home food consumption in the
      Northeast Region: an analysis of the 2008-2009 National Dietary Survey.
AB  - Introduction:: Away-from-home food consumption has increased in Brazil and is
      associated with fewer nutritious food choices. Objective:: To describe energy and
      specific nutrient intake among consumers and non-consumer of away-from-home food
      in the Northeast Region. Methods:: A sample of 11,674 individuals from the
      National Dietary Survey data, which is part of the 2008-2009 Household Budget
      Survey, from the Northeast Region, was analyzed. Individuals provided two dietary
      records in nonconsecutive days, informing the place where foods were consumed (at
      home or away-from-home). Away-from-home food was defined as foods acquired and
      consumed away from home. Linear regression models were developed to assess the
      relationship between away-from-home food consumption in one of the two-day food
      record and the energy and nutrient intake, adjusted for age, gender, and per
      capita income. Results:: Away-from-home food consumption, in at least one of the
      two-day food record, was reported by 42% of individuals in the Northeast Region.
      Individuals who consumed food away from home in the Northeast Region presented
      poor nutrient intake compared to those who did not report consumption away from
      home, with higher intake of energy, free sugar, saturated fat, and trans fat and
      lower intake of protein, iron, and dietary fiber, regardless of age, gender, and
      income (p < 0.05). Conclusion:: Away-from-home food consumption in the Northeast
      Region contributed to higher energy and poorer nutrient intake. Therefore, the
      development of public policies and strategies that favor health food choices when
      individuals eat away from home is necessary.

PMID- 28513800
TI  - Sociodemographic factors and functional capacity of elderly affected by stroke.
AB  - Introduction:: Diseases of old age have shown increasing prevalence in society.
      One of them is stroke, which can be conceptualized as the interruption of
      cerebral blood supply due to a leakage or blood vessel obstruction caused by
      clots. Objective:: To verify the associations between sociodemographic factors
      and the functional capacity of elderly affected by stroke. Methods:: This is an
      epidemiological, cross-sectional, and quantitative study, including 118 elderly
      people with paralyses due to stroke, who were registered in one of the Family
      Health Strategies units of Campina Grande, Paraiba, Brazil. Data were collected
      by means of home interviews. Two questionnaires were used, in which one was
      directed for assessment of sociodemographic variables and the second was called
      Barthel index for assessing the functional capacity of the subjects regarding the
      activities of daily life. The analysis was conducted using the statistical
      program SPSS. Results:: There was a predominance of the female gender, widowed,
      without schooling, and with household income of up to one Brazilian minimum wage.
      The average age was 65 years (+/- 9.63). The Barthel index internal consistency
      was satisfactory, presenting values of Cronbach's alpha coefficient in the range
      of 0.897-0.918. Total correlation of corrected items was greater than 0.4, and
      Cronbach's alpha with a deleted item was also greater than 0.8. The activities
      with higher level of achievement difficulty were urination and evacuation.
      Association between functional capacity with race, age range, and schooling was
      found. Conclusion:: It was seen that demographic factors might interfere with the
      functional capacity of elderly affected by stroke. Hence, it is believed that
      this investigation might have contributed to the reflection on this issue, thus
      supporting the promotion of these people's access to health assistance programs.

PMID- 28513801
TI  - Validity and reliability of a telephone survey of physical activity in Brazil.
AB  - Introduction:: Physical activity in Brazil is assessed by the Telephone-based
      Risk Factor Surveillance System for Chronic Diseases (VIGITEL). Objectives:: To
      evaluate the reliability and concurrent validity of VIGITEL physical activity
      indicators. Methods:: For the reliability study, 305 individuals responded to
      VIGITEL interviews, which were repeated with intervals of 7 - 15 days, in Belo
      Horizonte, 2013. The evaluated indicators included "sufficiently active on
      leisure time," "active in transportation," "inactive in four domains of physical
      activity (leisure, work, transportation, and housework)," and "watching TV for
      long periods." Kappa coefficient (k) was used to measure agreement between both
      interviews. For concurrent validity assessment, the same subjects also responded
      to the Global Physical Activity Questionnaire (GPAQ), used as reference method
      for comparison of VIGITEL indicators. Comparison was assessed by measures of
      sensitivity, specificity, positive (PPV), and negative predictive values (NPV).
      Results:: Reliability study showed substantial agreement for active individuals
      in leisure time (k = 0.70) and inactive individuals (k = 0.64). The agreement of
      watching TV for long periods was moderate (k = 0.56) and the activeness in
      transportation showed fair agreement (k = 0.35). In comparison to the reference
      method, sensitivity ranged from 54.8 to 67.7 in frequency of inactive, active in
      leisure time and work. Transportation domain was represented by 11.9 of
      sensitivity. Specificity ranged from 72.0 to 91.2 among four domains of physical
      activity and inactive. Conclusion:: Physical activity questionnaire used by the
      surveillance system seems to be reliable in all domains, except in transportation
      questions. VIGITEL was considered comparable to GPAQ in most aspects of physical
      activity evaluation.

PMID- 28513802
TI  - Prevalence and factors associated with self-reported disability: a comparison
      between genders.
AB  - Objective:: To estimate the prevalence of disability and its association with
      sociodemographic and health characteristics stratified by sex. Methods:: This is
      a cross-sectional study with a probabilistic sample including 4,048 residents
      aged >= 18 years in two health districts of Belo Horizonte (MG), Brazil, during
      the period from 2008 to 2009. The outcome variable "disability" was established
      based on self-reported problems in body functions or structures. Sociodemographic
      characteristics ("sex," "age," "skin color," "marital status," "years of
      schooling," and "family income") and health ("reported morbidity," "health self
      assessment," "quality of life," and "life satisfaction") were the explanatory
      variables. We applied the multivariate decision tree analysis by using the Chi
      square Automatic Interaction Detector algorithm. Results:: The overall prevalence
      of disability corresponded to 10.4% and it was higher in females (11.9%;
      confidence interval - 95%CI 10.2 - 13.6) than in males (8.7%; 95%CI 6.8 - 10.5).
      In the multivariate analysis, "age" and "morbidity" in females, and "low
      educational level" and "poor health self-assessment" in males were the variables
      that best discriminated disability. Disability self-reporting was more frequent
      among women of working age (40 to 59 years-old) and with lower incomes, as well
      as in men with lower educational levels and incomes. With regard to health
      conditions, the highest disability percentages were seen among subjects of both
      genders that reported three or more diseases and worsened perception of health.
      Conclusion:: Results reinforce the need for a distinct approach, since women of
      working age and men with lower educational level are more vulnerable to the
      occurrence of disability.

PMID- 28513803
TI  - Primary Health Care and tuberculosis: services evaluation.
AB  - Introduction:: In order to control tuberculosis, the Brazilian Ministry of Health
      recommends the decentralization of control actions directed to the Primary Health
      Care, and there are few studies on the performance of the Tuberculosis Control
      Program in decentralized contexts. Objective:: To evaluate the performance of
      Primary Health Care services in tuberculosis treatment. Methods:: This is an
      evaluative study with cross-sectional approach conducted in 2011. Two hundred and
      thirty-nine health professionals from Primary Health Care units were interviewed
      using a structured instrument based on the evaluation reference of the health
      services quality (structure - process - results). The performance of these
      services was analyzed applying techniques of descriptive statistics, validation,
      and construction of indicators and by determining the reduced variable "Z".
      Results:: The indicators "participation of professionals in tuberculosis
      patients' care" (structure) and "reference and counterreference" (process) had
      the best evaluations, whereas "professional training" (structure) and "external
      actions for tuberculosis control" (process) had the worst results. Conclusion::
      The decentralization of tuberculosis control actions has been taking place in a
      vertical manner in Primary Health Care. The challenge of controlling tuberculosis
      involves overcoming constraints related to the engagement, training, and turnover
      rates among health professionals, which is a coordination between services and
      monitoring of control actions in Primary Health Care.

PMID- 28513804
TI  - The Brazilian Oral Health Survey (SBBrasil 2010) workflow from the coordinators'
      perspective.
AB  - Introduction:: Although the workflow of population health surveys may interfere
      with the quality of the information produced, this aspect has not been
      investigated in the context of oral health. Objective:: To identify the
      perception of the Brazilian Oral Health Survey (SBBrasil 2010 Project)
      coordinators regarding the survey's workflow. Methods:: Data was collected using
      an electronic questionnaire sent to the coordinators after the national survey
      was completed. The variables investigated were grouped into themes spanning the
      various stages of the survey. Results:: The response rate was of 75.6% (n = 161).
      The majority of respondents worked as municipal coordinators in the survey
      (82.6%), were females (68%), worked as civil servants in the public health system
      (65.2%), and occupied managerial positions (75.8%). The reported positive aspects
      of the survey were: planning, training and calibration workshops; the logistic
      support provided by both the health system and the survey's coordination team;
      the positive relationship between staff members, as well as the survey's
      acceptance by respondents and health professionals. The financial assistance
      offered for transportation during the survey and issues related to the grants
      received by coordinators were seen as negative aspects to be overcome. Most of
      the respondents reported that the research experience was useful in qualifying
      staff services and showed interest in participating in future oral health
      surveys. Conclusion:: The coordinators' perception regarding their workflow in
      the SBBrasil 2010 Project was mainly positive. The results may contribute to the
      improvement of future oral health surveys.

PMID- 28513805
TI  - Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative
      Colitis. Part 2: Current Management.

PMID- 28513806
TI  - Increased activity of vascular adenosine deaminase in atherosclerosis and
      therapeutic potential of its inhibition.
AB  - Aims: Extracellular nucleotides and adenosine that are formed or degraded by
      membrane-bound ecto-enzymes could affect atherosclerosis by regulating the
      inflammation and thrombosis. This study aimed to evaluate a relation between ecto
      enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide
      phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the
      vessel wall with the severity or progression of experimental and clinical
      atherosclerosis. Furthermore, we tested whether the inhibition of adenosine
      deaminase will block the development of experimental atherosclerosis. Methods and
      results: Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase
      1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in
      aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-)
      and wild-type mice as well as in human aortas. Plaques were analysed in the
      entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein
      Martius Scarlet Blue staining and vascular accumulation of macrophages. The
      cellular location of ecto-enzymes was analysed by immunofluorescence. The effect
      of eADA inhibition on atherosclerosis progression was studied by a 2-month
      deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity
      prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already
      at the age of 1 month and progressed along atherosclerosis development, reaching
      a 10-fold difference at 10 months. The activity of eADA correlated with
      atherosclerotic changes in human aortas. High abundance of eADA in
      atherosclerotic vessels originated from activated endothelial cells and
      macrophages. There were no changes in ecto-nucleoside triphosphate
      diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately
      decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque
      development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice,
      suppressed vascular inflammation and improved endothelial function. Conclusions:
      This study highlights the importance of extracellular nucleotides and adenosine
      metabolism in the atherosclerotic vessel in both experimental and clinical
      setting. The increased eADA activity marks an early stage of atherosclerosis,
      contributes to its progression and could represent a novel target for therapy.

PMID- 28513807
TI  - The nuclear pore protein Nup153 associates with chromatin and regulates cardiac
      gene expression in dystrophic mdx hearts.
AB  - Aims: Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate
      gene expression and are involved in cardiac diseases. Notably, a number of
      cardiovascular disorders have been linked to alterations in epigenetic
      mechanisms. Here we aimed to determine the contribution of Nup153 to the
      epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx
      mice (C57BL/10ScSn-Dmd mdx /J). Methods and results: Nup153 was lysine-acetylated
      and its expression was significantly increased at protein level in mdx hearts
      compared with controls. Accordingly, lysine acetyl transferase (KAT) activity
      associated with Nup153 was higher in mdx hearts paralleling increased binding
      with the lysine acetylases P300/CBP-associated factor (PCAF) and p300.
      Interestingly, Nup153 silencing in mdx organotypic heart tissue slices caused a
      reduction in PCAF- and p300-specific activities. Remarkably, the level of nitric
      oxide (NO), which is reduced in mdx mice, was important for KAT-dependent
      regulation of Nup153. In fact, treatment of mdx heart tissue with an NO donor or
      the KAT inhibitor anacardic acid normalized Nup153 protein expression. Nup153 was
      recruited to chromatin and regulated the transcription of genes involved in
      cardiac remodelling, including the actin-binding protein nexilin. Accordingly,
      nexilin protein expression was abrogated by Nup153 silencing in mdx organotypic
      cultures. Electrophysiological and molecular experiments revealed that Nup153
      overexpression in normal cardiomyocytes increases Ca v 1.2 calcium channel
      expression and function. Alterations in Nup153 protein expression and
      intracellular localization were also found in dystrophic cardiomyocytes derived
      from patient-specific induced pluripotent stem cells. Importantly, Nup153 up
      regulation and increased acetylation were also found in the heart of Duchenne
      muscular dystrophy patients. Conclusions: Our data indicate that Nup153 is an
      epigenetic regulator which, upon altered NO signalling, mediates the activation
      of genes potentially associated with early dystrophic cardiac remodelling.

PMID- 28513808
TI  - Magnetic nanoparticle-enhanced PCR for the detection and identification of
      Staphylococcus aureus and Salmonella enteritidis.
AB  - This paper evaluated magnetic nanoparticle-enhanced PCR for the detection and
      identification of Staphylococcus aureus and Salmonella enteritidis. Two different
      types of magnetic nanoparticles designated MPIO (iron concentration 2.5 mg/ml,
      size 1 um) and NP (iron concentration 8.7 mg/ml, size 60 nm), both conjugated
      with S. aureus or S. enteritidis antibodies were evaluated as an enrichment
      procedure for PCR-detection of the pathogens in Trypticase Soy Broth, milk, blood
      and meat broth. Bacterial suspensions (1.5x108 cfu/ml) were prepared and serial
      diluted 10-1. The MPIO and NP nanoparticles were added, followed by incubation
      for 1 hour at room temperature, magnetic separation of the pellet, DNA extraction
      and PCR, targeting the femA and invA sequences. The nanoparticle-free and the NP
      supplemented dilutions were positive down to the 1.5x102 cfu/ml concentration for
      both bacteria. The MPIO-supplemented dilutions were positive down to approx.
      2x100 cfu/ml concentration, respectively. Bacteria-free TSB was negative by PCR.
      MPIO nanoparticles (size 1 um) enhanced the detection of S. aureus and S.
      enteritidis by PCR, whilst NP nanoparticles (size 60 nm) did not, thus indicating
      that the size of the magnetic nanoparticles play a significant role in the
      enrichment procedure.

PMID- 28513809
TI  - Oral gentamicin therapy for Carbapenem-resistant Klebsiella pneumoniae gut
      colonization in hematologic patients: a single center experience.
AB  - The mortality for carbapenem-resistant Klebsiella pneumoniae (KPC-Kp) infection
      ranges from 18 to 48% depending on the type of therapy. Mortality rates in
      hematologic patients are even higher, up to 85%. Gut decontamination with oral
      gentamicin might be an option to avoid a subsequent KPC-Kp infection in colonized
      patients. We treated 14 hematologic patients with oral gentamicin, 80 mg four
      times daily, for 7 to 25 days in order to eradicate KPC-Kp from the gut, starting
      oral gentamicin therapy when possible after the discontinuation of systemic
      antibiotic therapy. The overall decontamination rate in the entire study
      population was 71% (10/14). Out of the 4 patients who did not respond to oral
      gentamicin therapy, 1 KPC-Kp strain was gentamicin resistant and 4 patients
      received concomitant systemic antibiotic therapy (CSAT). One of these patients
      died from KPC-Kp sepsis. The decontamination rate was 90% (9/10) in patients
      receiving oral gentamicin only, versus 25% (1/4) in those also treated with CSAT.
      No new gentamicin-resistant KPC-Kp strain was isolated during oral gentamicin
      therapy Oral gentamicin might be useful for gut decontamination and prevention of
      KPC-Kp infection. This option should be considered in patients colonized by a
      gentamicin-susceptible KPC-Kp strain and not receiving CSAT.

PMID- 28513810
TI  - Epstein-Barr virus encephalitis in solid organ transplantation.
AB  - Epstein-Barr virus (EBV) is typically associated with post transplant
      lymphoproliferative disease (PTLD) after solid organ and stem cell
      transplantation. However, it is rarely associated with neurological
      complications. We report a case of severe encephalitis complicating primary EBV
      infection six months post renal transplantation, and review the literature on EBV
      encephalitis in solid organ transplantation in adults. A 55-year-old male
      presented 6 months post cadaveric renal transplant with headache, fever and
      confusion. Neuroimaging was unremarkable, but an electroencephalogram was
      consistent with diffuse encephalopathy. EBV DNA was detected in both
      cerebrospinal fluid (13,177 copies/ml), and plasma (14,166 copies/ml). Management
      included reduction of immunosuppression, intravenous ganciclovir and intravenous
      immunoglobulin, and resulted in a reduction in EBV viral load in both plasma and
      cerebrospinal fluid. The patient made a full recovery with no long-term
      neurological deficits and preservation of the graft. This case highlights the
      importance of knowing donor and recipient EBV serostatus at time of transplant,
      and closely monitoring EBV DNA when there is a mismatch. Ganciclovir or
      valganciclovir prophylaxis has also been shown to reduce the incidence of primary
      EBV infection in renal transplantation in these recipients. Treatment options for
      EBV infection post-transplant include reduction of immunosuppression, antiviral
      therapy, IVIg, and monoclonal antibody therapy directed toward infected B
      lymphocytes.

PMID- 28513811
TI  - An initially unidentified case of urinary tract infection due to Aerococcus
      urinae.
AB  - Aerococcus urinae is a microorganism responsible for urinary tract and blood
      stream infections which are rarely reported in clinical practice. However, it has
      been proposed that the infrequency of such reports may be partially due to
      difficulties related to pathogen identification. We present here a case of an
      elderly male patient with urinary tract infection where A. urinae was initially
      not identified by a private microbiology laboratory. Our report highlights the
      need to consider A. urinae as a causative agent of urinary tract infections
      because if not identified and properly treated it may lead to endocarditis or
      septicemia.

PMID- 28513812
TI  - Common dermatophytes and in vitro anti-fungal susceptibility testing in patients
      attending the Dermatological Clinic at the Hospital for Tropical Medicine,
      Bangkok.
AB  - Dermatophytes comprising the genera Trichophyton, Microsporum, and Epidermophyton
      are important causes of superficial mycoses. The number of infected patients and
      the distribution of species of these organisms in our hospital were unknown. We
      therefore aimed to investigate the clinical pattern of dermatophyte infections
      and to identify the species of these dermatophytes at the Dermatological Clinic
      of the Hospital for Tropical Medicine, Faculty of Tropical Medicine, Mahidol
      University, Bangkok in a 1-year period. Twenty-six patients who had typical
      dermatophytosis lesions were recruited (27 specimens); 17 were female (65.38%)
      and 9 (34.62%) were male. The age range of the patients was 16-92 years. In
      total, nine dermatophyte isolates were identified by macroscopic and microscopic
      morphological characteristics. We found Microsporum canis (four isolates),
      Trichophyton mentagrophytes complex (one), Trichophyton rubrum (two),
      Trichophyton verrucosum (one), and Trichophyton tonsurans (one). The in vitro
      susceptibility profiles of seven antifungal agents against the nine dermatophytes
      were as follows (minimum inhibitory concentration ranges in MUg/ml): The results
      were as follows (MIC ranges in MUg/ml): ciclopirox, <=0.06-0.5, griseofulvin
      <=0.06-0.5, itraconazole <=0.002-0.06, posaconazole <=0.015-0.03, voriconazole
      <=0.02->=1, fluconazole <=0.08-8, and terbinafine <=0.01-0.125. This study
      represents the current state of dermatophyte infections in a metropolitan area of
      Bangkok, Thailand.

PMID- 28513814
TI  - Zika virus isolation from semen.
AB  - Zika virus (ZIKV) can be sexually transmitted and replicative particles were
      first detected in a semen sample from a patient during the 2013-14 French
      Polynesia outbreak. Here we describe the virus isolation from semen of a patient
      returning to Italy from Brazil.

PMID- 28513813
TI  - Hepatitis B virus reactivation after effective sofosbuvir and ribavirin treatment
      in a patient with occult hepatitis B virus infection.
AB  - Reactivation of the hepatitis B virus (HBV) has been reported in patients with
      occult infection (OBI), i.e. HBV surface antigen (HBsAg) negative, HBV core
      antibody (anti-HBc) positive +/- antibodies against HBsAg (anti-HBs) and
      detectable HBV DNA in serum or liver, receiving immunosuppressive or cytotoxic
      therapies. Recently, concerns have been raised regarding the risk of HBV
      reactivation in OBI patients treated with direct acting antiviral agents (DAAs)
      for chronic hepatitis C (CHC). Here we describe a case of HBV reactivation in a
      72-year-old woman with OBI as a possible consequence of effective treatment with
      sofosbuvir (SOF) and ribavirin (Rbv) for genotype 2a/2c CHC.

PMID- 28513815
TI  - Epidemiology of paediatric meningitis in central Cote d'Ivoire after the
      implementation of Haemophilus influenzae type b vaccination.
AB  - Infectious meningitis accounts for enormous morbidity worldwide, but there is a
      paucity of data on its regional epidemiology in resource-constrained settings of
      sub-Saharan Africa. Here, we present a study on the aetiology of paediatric
      meningitis in central Cote d'Ivoire. Between June 2012 and December 2013, all
      cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital
      Bouake were examined for the presence of bacterial and fungal pathogens. A
      causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most
      prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria
      meningitidis (n=5). With the exception of neonates, these two bacteria were the
      most common agents in all age groups. Of note, only a single case of Haemophilus
      influenzae meningitis was detected. Hence, this study reports a considerable
      shift in the epidemiology of paediatric meningitis in central Cote d'Ivoire.
      Following the implementation of a nation-wide childhood vaccination programme
      against H. influenzae type b, this pathogen was much less frequently reported
      than in previous studies. The integration of specific vaccines against S.
      pneumoniae and N. meningitidis into the childhood vaccination programme in
      Coted'Ivoire holds promise to further reduce the burden due to infectious
      meningitis.

PMID- 28513817
TI  - Loss of permanent employment and its association with suicidal ideation: a cohort
      study in South Korea.
AB  - Objective Precarious employment is associated with worse mental health, but it is
      unclear whether changes in employment status are related to suicidal behaviors.
      This study examined the association between change in employment status and
      suicidal ideation among workers in South Korea. Methods To maximize power of the
      analysis, we combined data from the ongoing Korean Welfare Panel Study. We
      analyzed 3793 participants who were permanent workers at baseline (2011-2014) and
      who either: (i) maintained permanent employment; (ii) became a full-time
      precarious worker; (iii) became a part-time precarious worker; or (iv) became
      unemployed in the following year (2012-2015). Suicidal ideation was assessed
      annually by asking participants, "Have you ever seriously thought about dying by
      suicide in the past year?" Logistic regression was applied to examine
      associations between change in employment status and suicidal ideation, adjusting
      for potential confounders such as lifetime suicidal ideation and depressive
      symptoms at baseline. Results Participants who became part-time precarious
      workers were more likely to have suicidal ideation [odd ratio (OR) 2.37, 95%
      confidence interval (95% CI) 1.07-5.25, P=0.033] compared to those who remained
      permanent workers. In analysis restricted to workers who never previously thought
      about dying by suicide, suicidal ideation was more common among those who became
      either full-time (OR 2.33, 95% CI 1.09-4.99, P=0.029) or part-time (OR 3.94, 95%
      CI 1.46-10.64, P=0.007) precarious workers. Conclusions Our findings suggest that
      change in employment status from permanent to precarious employment may increase
      suicidal ideation among workers in South Korea.

PMID- 28513818
TI  - The risk of melanoma associated with ambient summer ultraviolet radiation.
AB  - BACKGROUND: Depletion of the ozone layer has meant that ambient ultraviolet
      radiation (UVR) has increased in recent decades. At the same time, the incidence
      of skin cancers, including melanoma, has risen. The relatively few large-scale
      studies that linked ambient UVR to melanoma found a trend toward rising incidence
      closer to the equator, where UVR estimates are highest. Similar research has not
      been conducted in Canada, where ambient UVR is generally lower than in countries
      further south. DATA AND METHODS: Modelled UVR data for the months of June through
      August during the 1980-to-1990 period were spatially linked in Geographic
      Information Systems to 2.4 million white members of the 1991 Canadian Census
      Health and Environment Cohort and tracked for melanoma diagnosis over an 18-year
      period (1992 to 2009). Standard Cox proportional hazards models were used to
      estimate melanoma risk associated with increases of ambient summer UVR, assigned
      by residence at baseline. Models were adjusted for age, sex and socioeconomic
      (SES) characteristics. Separate analyses by body site of melanoma were conducted.
      Effect modification of the association between ambient UVR and melanoma by sex,
      age, outdoor occupation and selected SES characteristics was evaluated. RESULTS:
      Differences of one standard deviation (446 J/m2, or 7% of the mean) in average
      ambient summer UVR were associated with an increased hazard ratio (HR) for
      melanoma of 1.22 (95% CI: 1.19 to 1.25) when adjusting for sex, age and SES
      characteristics. The HR for melanoma in relative UVR (per 1 standard deviation)
      was larger for men (HR = 1.26; 95% CI: 1.21 to 1.30) than for women (HR = 1.17;
      95% CI: 1.13 to 1.22). INTERPRETATION: Ambient summer UVR is associated with a
      greater risk of melanoma among the white population, even in a country where most
      people live within a narrow latitudinal belt. A stronger association between
      melanoma and ambient UVR was evident among men and among people of lower SES.

PMID- 28513819
TI  - Sun exposure, sun protection and sunburn among Canadian adults.
AB  - BACKGROUND: Ultraviolet radiation (UVR) exposure and a history of sunburn are
      important risk factors for skin cancer. Sunburn is more common among men, younger
      age groups, and people in higher income households. Sun protection measures also
      vary by sex, age, and socioeconomic characteristics. Associations between ambient
      UVR and sunburn and sun safety measures have not been quantified. DATA AND
      METHODS: A total of 53,130 respondents aged 18 or older answered a Canadian
      Community Health Survey (CCHS) module on sun safety, which was administered in
      six provinces from 2005 to 2014. The module contained questions about sunburn,
      time in the sun, and sun protection. These respondents were linked to an ambient
      erythemal UVR dataset representing the June-to-August mean. Descriptive
      statistics and logistic regression were used to examine associations between
      population characteristics, sunburn, sun safety, time in the sun, and ambient
      UVR. RESULTS: Sunburn was reported by 33% of respondents and was more common
      among men, younger age groups, people who were not members of visible minorities,
      residents of higher income households, and individuals who were employed. On a
      typical summer day, a larger percentage of women than men sought shade and wore
      sunscreen, whereas a larger percentage of men wore a hat or long pants. As
      ambient summer UVR increased, women were more likely to apply sunscreen to their
      face, seek shade, or wear a hat (OR~1.02 to 1.09 per increase of 187 J/m2 of
      erythemally-weighted UVR, or 5.4% of the mean); these associations were not
      observed among men. INTERPRETATION: Findings related to sunburn and sun
      protection were similar to those of previous studies. The association between
      ambient UVR and women's precautionary measures suggests that information about
      UVR may influence their decision to protect their skin.

PMID- 28513816
TI  - Italian guidelines for the use of antiretroviral agents and the diagnostic
      clinical management of HIV-1 infected persons. Update 2016.
AB  - The Italian Society of Infectious and Tropical Diseases (SIMIT) of the Technical
      Health Committee, Ministry of Health (Sections L and M) of Italy have supported
      recommendations for the Italian guidelines for the use of antiretroviral agents
      and the diagnostic-clinical management of HIV-1 infected persons. This
      publication summarizes the latest updates to the 2016 version of the Italian
      Guidelines for the management of HIV-1 infected patients and the use of
      antiretroviral drugs. In particular, new recommendations were released concerning
      the following topics: estimate of the HIV continuum of care in Italy, optimal
      timing and preferred drug combinations for starting antiretroviral therapy,
      treatment optimization, and pre-exposure prophilaxis (PrEP). For a complete
      review of clinical and therapeutic relevant topics we refer the reader to the
      extended version of the Guidelines.

PMID- 28513820
TI  - Intra-abdominal hypertension and abdominal compartment syndrome in acute
      pancreatitis, hepato-pancreato-biliary operations and liver transplantation.
AB  - Intra-abdominal hypertension, even preceding the onset of abdominal compartment
      syndrome, is still recognized as an adverse prognostic factor. Unfortunately,
      most of the current supporting evidence within the critical care environment
      remains observational in nature. In acute pancreatitis, an active role for intra
      abdominal hypertension early in the disease process follows a strong intuitive
      basis, and it is corroborated by preliminary evidence from animal models.
      Additional studies are needed to better characterize the optimal fluid
      resuscitation strategy, as well as the importance of intra-abdominal hypertension
      as an early therapeutic target. All critically ill patients with acute
      pancreatitis should be considered for routine intra-abdominal pressure
      monitoring. The prevalence and clinical relevance of intra-abdominal hypertension
      after elective major abdominal operations are underestimated in the literature.
      Hepato-pancreato-biliary surgery and liver transplantation represent high-risk
      surgical subspecialties, and routine intra-abdominal hypertension risk assessment
      to indicate postoperative intra-abdominal pressure monitoring can be recommended.
      Conservative management of intra-abdominal hypertension should be promptly
      initiated upon diagnosis. Although abdominal catheter drainage and decompressive
      laparotomy may be required in refractory cases based on expert clinical judgment,
      precise indications and timing are still unclear. Implementation of institutional
      protocols based on the Abdominal Compartment Society reference standards is
      crucial to optimize both clinical management and research in this evolving area.

PMID- 28513822
TI  - Abdominal pressure and gastrointestinal function: an inseparable couple?
AB  - Evaluating the degree of organ dysfunction is a cornerstone in distinguishing
      patients with critical illness from those without. However, evaluation of the
      gastrointestinal function in critically ill patients is not unified, and is still
      largely based on subjective clinical evaluation. Although intra-abdominal
      pressure has been proposed as a parameter to facilitate monitoring of abdominal
      compartment in critical illness, the interactions between intra-abdominal
      pressure and gastrointestinal function are poorly clarified. The aim of this
      current review is to describe interactions and associations between
      gastrointestinal dysfunction and intra-abdominal pressure from a
      pathophysiological and clinical point of view.

PMID- 28513821
TI  - Platelets in sepsis - are there any new aspects?
AB  - Platelets display a number of properties besides the crucial function of
      repairing a damaged vascular endothelium and stopping bleeding. Platelets
      constitutively express molecules that are classically acknowledged to function in
      primary haemostasis. Platelets specialize in pro-inflammatory activities, and can
      secrete a large number of molecules, many of which display biological response
      modifier functions. Recently, platelets expressing receptors for infectious and
      possibly noninfectious danger signals were shown to be involved in
      pathophysiological reactions including an immune-inflammatory response. In
      sepsis, platelets play a key role in immunothrombosis, participate in the
      formation of NETs (neutrophil extracellular trap) resulting in the trapping and
      killing of pathogens and are one of the main factors influencing mortality.

PMID- 28513824
TI  - How we treat germ cell cancers.

PMID- 28513823
TI  - Adjuvant radiotherapy improves overall survival in patients with resected gastric
      adenocarcinoma: A National Cancer Data Base analysis.
AB  - BACKGROUND: For patients with resectable gastric adenocarcinoma, perioperative
      chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard
      options. In the current study, the authors used the National Cancer Data Base to
      compare overall survival (OS) between these regimens. METHODS: Patients who
      underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through
      2012 were divided into those treated with perioperative chemotherapy without RT
      versus those treated with adjuvant CRT. Survival was estimated and compared using
      univariate and multivariate models adjusted for patient and tumor
      characteristics, surgical margin status, and the number of lymph nodes examined.
      Subset analyses were performed for factors chosen a priori, and potential
      interactions between treatment and covariates were assessed. RESULTS: A total of
      3656 eligible patients were identified, 52% of whom underwent perioperative
      chemotherapy and 48% of whom received postoperative CRT. The median follow-up was
      47 months, and the median age of the patients was 62 years. Analysis of the
      entire cohort demonstrated improved OS with adjuvant RT on both univariate
      (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio,
      0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity
      score-matched analysis also demonstrated improved OS with adjuvant RT (median of
      49 months vs 39 months; P = .033). On subset analysis, a significant interaction
      was observed between the survival impact of adjuvant RT and surgical margins,
      with a greater benefit of RT noted among patients with surgical margin-positive
      disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001).
      CONCLUSIONS: In this National Cancer Data Base analysis, the use of adjuvant RT
      in addition to chemotherapy was associated with a significant OS advantage for
      patients with resected gastric cancer. The survival advantage observed with
      adjuvant CRT was most pronounced among patients with positive surgical margins.
      Cancer 2017;123:3402-9. (c) 2017 American Cancer Society.

PMID- 28513826
TI  - Noncontingent reinforcement without extinction plus differential reinforcement of
      alternative behavior during treatment of problem behavior.
AB  - The effects of noncontingent reinforcement (NCR) without extinction during
      treatment of problem behavior maintained by social positive reinforcement were
      evaluated for five individuals diagnosed with autism spectrum disorder. A
      continuous NCR schedule was gradually thinned to a fixed-time 5-min schedule. If
      problem behavior increased during NCR schedule thinning, a continuous NCR
      schedule was reinstated and NCR schedule thinning was repeated with differential
      reinforcement of alternative behavior (DRA) included. Results showed an immediate
      decrease in all participants' problem behavior during continuous NCR, and problem
      behavior maintained at low levels during NCR schedule thinning for three
      participants. Problem behavior increased and maintained at higher rates during
      NCR schedule thinning for two other participants; however, the addition of DRA to
      the intervention resulted in decreased problem behavior and increased mands.

PMID- 28513825
TI  - Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated
      down-regulation of E-cadherin.
AB  - Epigenetic modifications such as histone modifications and cytosine
      hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine
      (5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor
      initiation and development. However, the mechanisms by which loss of TET1
      knockdown promotes malignancy development remains unclear. Here, we report that
      TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased
      cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased
      EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri
      methylation causing repression of the target gene E-cadherin. Ectopic expression
      of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused
      a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby
      suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion
      and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells.
      These findings provide insight into the regulation of TET1 and E-cadherin and
      identify EZH2 as a critical mediator of E-cadherin repression and tumor
      progression.

PMID- 28513827
TI  - Using the dual-criteria methods to supplement visual inspection: An analysis of
      nonsimulated data.
AB  - The purpose of our study was to examine the probability of observing false
      positives in nonsimulated data using the dual-criteria methods. We extracted data
      from published studies to produce a series of 16,927 datasets and then assessed
      the proportion of false positives for various phase lengths. Our results indicate
      that collecting at least three data points in the first phase (Phase A) and at
      least five data points in the second phase (Phase B) is generally sufficient to
      produce acceptable levels of false positives.

PMID- 28513829
TI  - An analysis of procedures that affect response variability.
AB  - Response variability is sensitive to antecedent and consequent manipulations.
      Researchers have investigated inducement, direct production through
      reinforcement, and stimulus control of response variability. Recently,
      researchers have shown that lag reinforcement schedules reliably increase
      variability but may also produce higher-order stereotypy. There has been limited
      investigation of appropriate variability levels and alternation between
      repetition and variation. In a three-part study, we evaluated levels of
      variability across a group of children, the effects of various procedures on
      producing response variability and novelty, and the use of schedule-correlated
      stimuli for producing rapid alternation between repetition and variation. In
      Study 1, there was a nearly bimodal distribution of children emitting either low
      or high variability. In Study 2, for most children, fixed lag 4 and variable lag
      4 schedules produced the highest levels of variability and novelty. In Study 3,
      responding was brought under control of schedule-correlated stimuli, allowing for
      rapid alternation between repetition and variation.

PMID- 28513828
TI  - Outcome of autologous hematopoietic stem cell transplantation in refractory
      multiple myeloma.
AB  - BACKGROUND: Despite the introduction of effective, novel agents, the outcome of
      patients with refractory multiple myeloma remains poor, particularly those who
      are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents
      (IMiDs). Limited data are available on the role of autologous hematopoietic stem
      cell transplantation in this population. METHODS: Patients with refractory
      myeloma who underwent first autologous hematopoietic stem cell transplantation
      (auto-HCT) between March 2000 and October 2015 were retrospectively analyzed.
      Those who had primary refractory disease and those with relapsed and refractory
      disease were included. Disease that was refractory to at least 1 PI and at least
      1 IMiD was classified as double-refractory multiple myeloma (DR-MM). RESULTS: In
      total, 233 patients were identified, including 105 (45%) classified with DR-MM
      and 128 (55%) classified with nondouble-refractory myeloma (NDR-MM). At a median
      follow-up of 42 months for surviving patients, at least a partial response was
      observed in 188 patients (81%; 83 patients in the DR-MM group [79%] and 105
      patients in the NDR-MM [82%]; P = .77). A near complete response or better was
      observed in 52 patients (22%; 25 patients in the DR-MM group [24%] and 27
      patients in the NDR-MM group [21%]; P = .77). The median progression-free
      survival was 17.6 months (14.4 months in the DR-MM group and 18.2 months in the
      NDR-MM group), and the 2-year progression-free survival rate was 38% (35% in the
      DR-MM group and 40% in the NDR-MM group; P = .40). The median overall survival
      was 48 months (38.9 months in the DR-MM group and 56.6 months in the NDR-MM
      group), and the 2-year overall survival rate was 74% (71% in the DR-MM group and
      76% in the NDR-MM group; P = .27). CONCLUSIONS: The current findings indicate
      that auto-HCT is an effective and safe therapy in patients with refractory
      multiple myeloma, including those who are refractory to IMiDs and PIs. Cancer
      2017;123:3568-75. (c) 2017 American Cancer Society.

PMID- 28513831
TI  - Avoidance versus use of neuromuscular blocking agents for improving conditions
      during tracheal intubation or direct laryngoscopy in adults and adolescents.
AB  - BACKGROUND: Tracheal intubation during induction of general anaesthesia is a
      vital procedure performed to secure a patient's airway. Several studies have
      identified difficult tracheal intubation (DTI) or failed tracheal intubation as
      one of the major contributors to anaesthesia-related mortality and morbidity. Use
      of neuromuscular blocking agents (NMBA) to facilitate tracheal intubation is a
      widely accepted practice. However, because of adverse effects, NMBA may be
      undesirable. Cohort studies have indicated that avoiding NMBA is an independent
      risk factor for difficult and failed tracheal intubation. However, no systematic
      review of randomized trials has evaluated conditions for tracheal intubation,
      possible adverse effects, and postoperative discomfort. OBJECTIVES: To evaluate
      the effects of avoiding neuromuscular blocking agents (NMBA) versus using NMBA on
      difficult tracheal intubation (DTI) for adults and adolescents allocated to
      tracheal intubation with direct laryngoscopy. To look at various outcomes,
      conduct subgroup and sensitivity analyses, examine the role of bias, and apply
      trial sequential analysis (TSA) to examine the level of available evidence for
      this intervention. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS,
      International Web of Science, LILACS, advanced Google, CINAHL, and the following
      trial registries: Current Controlled Trials; ClinicalTrials.gov; and
      www.centerwatch.com, up to January 2017. We checked the reference lists of
      included trials and reviews to look for unidentified trials. SELECTION CRITERIA:
      We included randomized controlled trials (RCTs) that compared the effects of
      avoiding versus using NMBA in participants 14 years of age or older. DATA
      COLLECTION AND ANALYSIS: Two review authors extracted data independently. We
      conducted random-effects and fixed-effect meta-analyses and calculated risk
      ratios (RRs) and their 95% confidence intervals (CIs). We used published data and
      data obtained by contacting trial authors. To minimize the risk of systematic
      error, we assessed the risk of bias of included trials. To reduce the risk of
      random errors caused by sparse data and repetitive updating of cumulative meta
      analyses, we applied TSA. MAIN RESULTS: We identified 34 RCTs with 3565
      participants that met our inclusion criteria. All trials reported on conditions
      for tracheal intubation; seven trials with 846 participants described 'events of
      upper airway discomfort or injury', and 13 trials with 1308 participants reported
      on direct laryngoscopy. All trials used a parallel design. We identified 18 dose
      finding studies that included more interventions or control groups or both. All
      trials except three included only American Society of Anesthesiologists (ASA)
      class I and II participants, 25 trials excluded participants with anticipated
      DTI, and obesity or overweight was an excluding factor in 13 studies. Eighteen
      trials used suxamethonium, and 18 trials used non-depolarizing NMBA.Trials with
      an overall low risk of bias reported significantly increased risk of DTI with no
      use of NMBA (random-effects model) (RR 13.27, 95% CI 8.19 to 21.49; P < 0.00001;
      508 participants; four trials; number needed to treat for an additional harmful
      outcome (NNTH) = 1.9, I2 = 0%, D2 = 0%, GRADE = moderate). The TSA-adjusted CI
      for the RR was 1.85 to 95.04. Inclusion of all trials resulted in confirmation of
      results and of significantly increased risk of DTI when an NMBA was avoided
      (random-effects model) (RR 5.00, 95% CI 3.49 to 7.15; P < 0.00001; 3565
      participants; 34 trials; NNTH = 6.3, I2 = 70%, D2 = 82%, GRADE = low). Again the
      cumulative z-curve crossed the TSA monitoring boundary, demonstrating harmful
      effects of avoiding NMBA on the proportion of DTI with minimal risk of random
      error. We categorized only one trial reporting on upper airway discomfort or
      injury as having overall low risk of bias. Inclusion of all trials revealed
      significant risk of upper airway discomfort or injury when an NMBA was avoided
      (random-effects model) (RR 1.37, 95% CI 1.09 to 1.74; P = 0.008; 846
      participants; seven trials; NNTH = 9.1, I2 = 13%, GRADE = moderate). The TSA
      adjusted CI for the RR was 1.00 to 1.85. None of these trials reported mortality.
      In terms of our secondary outcome 'difficult laryngoscopy', we categorized only
      one trial as having overall low risk of bias. All trials avoiding NMBA were
      significantly associated with difficult laryngoscopy (random-effects model) (RR
      2.54, 95% CI 1.53 to 4.21; P = 0.0003; 1308 participants; 13 trials; NNTH = 25.6,
      I2 = 0%, D2= 0%, GRADE = low); however, TSA showed that only 6% of the
      information size required to detect or reject a 20% relative risk reduction (RRR)
      was accrued, and the trial sequential monitoring boundary was not crossed.
      AUTHORS' CONCLUSIONS: This review supports that use of an NMBA may create the
      best conditions for tracheal intubation and may reduce the risk of upper airway
      discomfort or injury following tracheal intubation. Study results were
      characterized by indirectness, heterogeneity, and high or uncertain risk of bias
      concerning our primary outcome describing difficult tracheal intubation.
      Therefore, we categorized the GRADE classification of quality of evidence as
      moderate to low. In light of defined outcomes of individual included trials, our
      primary outcomes may not reflect a situation that many clinicians consider to be
      an actual difficult tracheal intubation by which the patient's life or health may
      be threatened.

PMID- 28513830
TI  - Association between mutations of critical pathway genes and survival outcomes
      according to the tumor location in colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) develops through the alteration of several
      critical pathways. This study was aimed at evaluating the influence of critical
      pathways on survival outcomes for patients with CRC. METHODS: Targeted next
      generation sequencing of 40 genes included in the 5 critical pathways of CRC
      (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and
      transforming growth factor beta [TGF-beta]) was performed for 516 patients with
      stage III or high-risk stage II CRC treated with surgery followed by adjuvant
      fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical
      pathway mutations and relapse-free survival (RFS) and overall survival were
      analyzed. The associations were further analyzed according to the tumor location.
      RESULTS: The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-beta
      pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in
      the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR],
      0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS
      pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52).
      Proximal tumors showed a higher mutation rate than distal tumors, and the
      mutation profile was different according to the tumor location. The mutation
      rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol
      4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and B-Raf proto
      oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the
      mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and
      neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The
      better RFS with the PI3K pathway mutation was significant only for proximal
      tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only
      for distal tumors. CONCLUSIONS: A PI3K pathway mutation was associated with
      better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK-RAS
      pathway mutation was associated with worse RFS. The significance of the
      prognostic impact differed according to the tumor location. Cancer 2017;123:3513
      23. (c) 2017 American Cancer Society.

PMID- 28513832
TI  - Endless forms most hidden: katydids that masquerade as moss.

PMID- 28513833
TI  - Potential role and prognostic importance of dishevelled-2 in epithelial ovarian
      cancer.
AB  - OBJECTIVE: To investigate the role and prognostic importance of Dvl2 in human
      epithelial ovarian cancer (EOC). METHODS: A multimethod study was undertaken
      including patients with pathologically confirmed non-metastatic EOC who underwent
      surgery for maximum tumor resection at a center in China. Dvl2 expression was
      assessed by western blot using fresh EOC tissues and normal ovarian tissues
      obtained between June 2014 and January 2015. Additionally, retrospective data
      were obtained for patients treated between April 2004 and September 2009. Their
      tumor specimens were used in immunohistochemistry analysis. Kaplan-Meier survival
      plots were constructed to estimate the overall survival by Dvl2 expression, and a
      Cox proportional hazards model was used to analyze prognostic factors.
      Alterations in Dvl2 expression during the cell cycle were assessed by a
      starvation and refeeding assay. RESULTS: Dvl2 expression was higher in EOC
      samples than in normal tissues on western blot. Overall, 124 patients were
      included in immunohistochemistry analysis, and Dvl2 expression level was
      significantly associated with the tumor grade and Ki-67 expression.
      Overexpression of Dvl2 was correlated with poor prognosis. The pattern of Dvl2
      expression throughout the cell cycle matched that of the cell proliferation
      marker cyclin D1. CONCLUSION: Dvl2 could play a part in EOC progression and might
      be an independent prognostic factor. Additionally, it might be a prospective
      therapeutic target in the treatment of EOC.

PMID- 28513834
TI  - The association between complications and quality of life after mastectomy and
      breast reconstruction for breast cancer.
AB  - BACKGROUND: Medical treatment for breast cancer is associated with substantial
      toxicity and patient burden. There is less known about the impact of surgical
      complications. Understanding this impact could provide important information for
      patients when they are considering surgical options. METHODS: Between 2008 and
      2009, the UK National Mastectomy and Breast Reconstruction Audit recorded
      surgical complications for a prospective cohort of 17,844 women treated for
      breast cancer at 270 hospitals; 6405 of these women were surveyed about their
      quality of life 18 months after surgery. Breast appearance, emotional well-being,
      and physical well-being were quantified on 0- to 100-point scales. Linear
      multiple regression models, controlling for a range of baseline prognostic
      factors, were used to compare the scores of patients who had complications with
      the scores of those who did not. RESULTS: The overall complication rate was
      10.2%. Complications were associated with little or no impairment in women
      undergoing mastectomy without reconstruction or with delayed reconstruction. The
      association was much larger for flap-related complications suffered during
      immediate reconstruction. The breast-appearance scores (adjusted mean difference,
      -23.8; 95% confidence interval [CI], -31.0 to -16.6) and emotional well-being
      scores (adjusted mean difference, -14.0; 95% CI, -22.0 to -6.0) of these patients
      were much lower than those of any other patient group. Implant-related
      complications were not associated with a lower quality of life in any surgical
      group. CONCLUSIONS: There is a strong case for prospectively collecting flap
      complication rates at the surgeon and surgical unit level and for allowing
      patients to access these data when they make choices about their breast cancer
      surgery. Cancer 2017;123:3460-7. (c) 2017 American Cancer Society.

PMID- 28513835
TI  - British Association of Dermatologists guidelines for biologic therapy for
      psoriasis 2017.

PMID- 28513839
TI  - Improving Specialty Care of Older Adults: Creating Champions, Supporting
      Research, Fostering Partnerships.

PMID- 28513838
TI  - The emerging role of NPNT in tissue injury repair and bone homeostasis.
AB  - Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an
      important role in regulating cell adhesion, differentiation, spreading, and
      survival. NPNT protein belongs to the epidermal growth factor (EGF)-like
      superfamily and exhibits several common structural determinants; including EGF
      like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein
      Tyrosine Phosphatase u), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It
      regulates integrins-mediated signaling pathways via the interaction of its RGD
      motif with integrin alpha8beta1. Recent studies revealed that NPNT is involved in
      kidney development, renal injury repair, atrioventricular canal differentiation,
      pulmonary function, and muscle cell niche maintenance. Moreover, NPNT regulates
      osteoblast differentiation and mineralization, as well as osteogenic
      angiogenesis. Altered expression of NPNT has been linked with the progression of
      certain types of cancers, such as spontaneous breast tumor metastasis and
      malignant melanoma. Interestingly, NPNT gene expression can be regulated by a
      range of external factors such as tumor necrosis factor alpha (TNF-alpha),
      transforming growth factor beta (TGF-beta), oncostatin M (OSM), bone morphogenic
      protein 2 (BMP2), Wnt3a, Vitamin D3 , and microRNA-378 (miR378). Further
      understanding the cellular and molecular mechanisms by which NPNT regulates
      tissue homeostasis in an organ-specific manner is critical in exploring NPNT as a
      therapeutic target for tissue regeneration and tissue engineering.

PMID- 28513836
TI  - Facilitation of mossy fibre-driven spiking in the cerebellar nuclei by the
      synchrony of inhibition.
AB  - KEY POINTS: Large premotor neurons of the cerebellar nuclei (CbN cells) integrate
      synaptic inhibition from Purkinje neurons and synaptic excitation from mossy
      fibres to generate cerebellar output. We find that mossy fibre inputs to CbN
      cells generate unitary AMPA receptor EPSCs of ~1 nS that decay in ~1 ms and
      mildly voltage-dependent NMDA receptor EPSCs of ~0.6 nS that decay in ~7 ms. A
      few hundred mossy fibres active at a few tens of spikes s-1 must converge on CbN
      cells to generate physiological CbN spike rates (~60 spikes s-1 ) during
      convergent inhibition from spontaneously active Purkinje cells. Dynamic clamp
      studies in cerebellar slices from weanling mice demonstrate that synaptic
      excitation from mossy fibres becomes more effective at increasing the rate of CbN
      cell spiking when the coherence (synchrony) of convergent inhibition is
      increased. ABSTRACT: Large projection neurons of the cerebellar nuclei (CbN
      cells), whose activity generates movement, are inhibited by Purkinje cells and
      excited by mossy fibres. The high convergence, firing rates and strength of
      Purkinje inputs predict powerful suppression of CbN cell spiking, raising the
      question of what activity patterns favour excitation over inhibition. Recording
      from CbN cells at near-physiological temperatures in cerebellar slices from
      weanling mice, we measured the amplitude, kinetics, voltage dependence and short
      term plasticity of mossy fibre-mediated EPSCs. Unitary EPSCs were small and brief
      (AMPA receptor, ~1 nS, ~1 ms; NMDA receptor, ~0.6 nS, ~7 ms) and depressed
      moderately. Using these experimentally measured parameters, we applied
      combinations of excitation and inhibition to CbN cells with dynamic clamp.
      Because Purkinje cells can fire coincident simple spikes during cerebellar
      behaviours, we varied the proportion (0-20 of 40) and precision (0-4 ms jitter)
      of synchrony of inhibitory inputs, along with the rates (0-100 spikes s-1 ) and
      number (0-800) of excitatory inputs. Even with inhibition constant, when
      inhibitory synchrony was higher, excitation increased CbN cell firing rates more
      effectively. Partial inhibitory synchrony also dictated CbN cell spike timing,
      even with physiological rates of excitation. These effects were present with >=10
      inhibitory inputs active within 2-4 ms of each other. Conversely, spiking was
      most effectively suppressed when inhibition was maximally asynchronous. Thus, the
      rate and relative timing of Purkinje-mediated inhibition set the rate and timing
      of cerebellar output. The results suggest that increased coherence of Purkinje
      cell activity can facilitate mossy fibre-driven spiking by CbN cells, in turn
      driving movements.

PMID- 28513837
TI  - Maternal near miss in low-resource areas.
AB  - OBJECTIVE: To describe the Global Network Near-Miss Maternal Mortality System and
      its application in seven sites. METHODS: In a population-based study, pregnant
      women eligible for enrollment in the Maternal and Newborn Health Registry at
      seven sites (Democratic Republic of the Congo; Guatemala; Belagavi and Nagpur,
      India; Kenya; Pakistan; and Zambia) between January 2014 and April 2016 were
      screened to identify those likely to have a near-miss event. The WHO maternal
      near-miss criteria were modified for low-resource settings. The ratio of near
      miss events to maternal deaths was calculated. RESULTS: Among 122 707 women
      screened, 18 307 (15.0%) had a potential near-miss event, of whom 4866 (26.6%;
      4.0% of all women) had a near-miss maternal event. The overall maternal mortality
      ratio was 155 per 100 000 live births. The ratio of near-miss events to maternal
      deaths was 26 to 1. The most common factors involved in near-miss cases were the
      hematologic/coagulation system, infection, and cardiovascular system. CONCLUSION:
      By using the Global Network Near-Miss Maternal Mortality System, large numbers of
      women were screened for near-miss events, including those delivering at home or a
      low-level maternity clinic. The 4.0% incidence of near-miss maternal mortality is
      similar to previously reported data. The ratio of 26 near-miss cases to 1
      maternal death suggests that near miss might evaluate the impact of interventions
      more efficiently than maternal mortality.

PMID- 28513841
TI  - Incorporating multiple secondary targets into learning trials for individuals
      with autism spectrum disorder.
AB  - The current study examined the outcome of presenting multiple secondary targets
      in learning trials for individuals with autism spectrum disorder. We compared
      conditions in which (a) a secondary target was presented in the antecedent and
      consequence of trials, (b) two secondary targets were presented in the
      consequence of trials, (c) one secondary target was presented in the consequence
      of each trial, and (d) no additional targets were presented trials. The
      participants acquired the majority of secondary targets. Presenting one or
      multiple secondary targets per trial, regardless of the location of these
      secondary targets, increased the efficiency of instruction in comparison to a
      condition with no secondary target.

PMID- 28513842
TI  - Expanding the Field of Surgical Researchers: The Jahnigen Career Development
      Award.
AB  - Under a long-standing collaboration with the John A. Hartford Foundation (JAHF),
      the Atlantic Philanthropies (AP), and specialty societies in 10 targeted
      specialties, the American Geriatrics Society (AGS) has been working to improve
      quality of care provided to older adults by surgical and related medical
      specialists. To support and nurture future academic leaders, the Geriatrics-for
      Specialists Initiative (GSI) established the Dennis W. Jahnigen Career
      Development Scholar Award (JCDA) program in 2002, with AP joining JAHF as a core
      funder of the awards in 2003. Commencing in 2011, the National Institute on Aging
      (NIA) launched the Grants for Early Medical/Surgical Specialists' Transition to
      Aging Research (GEMSSTAR) program, using an RO3 mechanism. Recipients of the JCDA
      and the GEMSSTAR are provided with 2 years of research support and networking
      opportunities with other scholars; 79 JCDA and 26 surgical and related medical
      specialty GEMSSTAR scholars have been funded through these award mechanisms, with
      AGS, JAHF, and surgical and related medical specialty societies providing
      matching support for 20 of the GEMSSTAR scholars for leadership development
      programs. One of the primary criteria for judging the overall success of the
      program was eventual transition of the award to a federally funded program, which
      was achieved when NIA launched the GEMSSTAR program in 2011.

PMID- 28513840
TI  - Histomorphology and innate immunity during the progression of osteoarthritis:
      Does synovitis affect cartilage degradation?
AB  - Osteoarthritis (OA) is a common chronic degenerative disease that affects all
      joints. At present, the pathological processes and mechanisms of OA are still
      unclear. Innate immunity, a key player in damage to the structure of the joint
      and the mechanism by which the host attempts to repair OA, affects all
      pathological stages of the disease. In the present study, our aim was to assess
      changes in innate immunity during the pathological processes of OA in articular
      cartilage (AC) and the synovial membrane (SM), which are the major structures in
      joints, and to systematically examine the histological changes in AC and SM in
      mild, moderate and severe cases of OA, in order to further speculate about the
      manner in which the interactions of AC and SM are facilitated by innate immunity.
      Histological methods (including HE and Safranin O-fast green staining),
      immunofluorescent double staining, TUNEL stain, and Western blots were used to
      assess the morphological changes within AC and SM tissues in healthy and mild,
      moderate, or severe OA rats. Our results showed that the damage to AC and SM
      within the joints progressively worsened in different degrees during the course
      of the disease, and that the innate immune system was closely involved in the AC
      and SM during each stage of OA. These findings also confirmed that SM may affect
      the pathological changes in AC through the innate immune system, and therefore
      affect the progress of OA.

PMID- 28513843
TI  - Meeting the Need for Training in Geriatrics: The Geriatrics Education for
      Specialty Residents Program.
AB  - The imperative created by increasing numbers of aging Americans coupled with
      increasing longevity has generated recognition and acceptance within american
      medicine that education, from medical school through postgraduate training
      through continuing medical education, must include appropriate knowledge and
      skills in aging and geriatrics to provide for effective care of older adults.
      Such education and training is necessary not only for traditional primary care
      providers, but also for specialty physicians, including those in most surgical
      specialties and in related fields such as anesthesiology, emergency medicine and
      physical medicine and rehabilitation. To fill this demand, the American
      Geriatrics Society Geriatrics for Specialist Initiative established the
      Geriatrics Education for Specialty Residents Program (GSR). This article reviews
      the process by which the GSR created a dynamic cohort of geriatric surgical
      educators and researchers who in turn created a vibrant body of educational tools
      and scientific works that continue to advance the cause of improving medical care
      of older adults.

PMID- 28513845
TI  - Claud S. Rupert (1919-2017): The Father of DNA Repair.

PMID- 28513846
TI  - A calmodulin-like protein regulates plasmodesmal closure during bacterial immune
      responses.
AB  - Plants sense microbial signatures via activation of pattern recognition receptors
      (PPRs), which trigger a range of cellular defences. One response is the closure
      of plasmodesmata, which reduces symplastic connectivity and the capacity for
      direct molecular exchange between host cells. Plasmodesmal flux is regulated by a
      variety of environmental cues but the downstream signalling pathways are poorly
      defined, especially the way in which calcium regulates plasmodesmal closure.
      Here, we identify that closure of plasmodesmata in response to bacterial
      flagellin, but not fungal chitin, is mediated by a plasmodesmal-localized Ca2+ 
      binding protein Calmodulin-like 41 (CML41). CML41 is transcriptionally
      upregulated by flg22 and facilitates rapid callose deposition at plasmodesmata
      following flg22 treatment. CML41 acts independently of other defence responses
      triggered by flg22 perception and reduces bacterial infection. We propose that
      CML41 enables Ca2+ -signalling specificity during bacterial pathogen attack and
      is required for a complete defence response against Pseudomonas syringae.

PMID- 28513848
TI  - Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and
      molecular diagnostics in allergic bronchopulmonary aspergillosis.
AB  - A wide spectrum of pathological conditions may result from the interaction of
      Aspergillus fumigatus and the immune system of its human host. Allergic
      bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related
      diseases due to possible evolution toward pleuropulmonary fibrosis and
      respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost
      exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of
      patients with cystic fibrosis experience this condition. The diagnosis of
      allergic bronchopulmonary aspergillosis relies on criteria first established in
      1977. Progress in the understanding of host-pathogen interactions in A. fumigatus
      and patients with cystic fibrosis and the ongoing validation of novel laboratory
      tools concur to update and improve the diagnosis of allergic bronchopulmonary
      aspergillosis.

PMID- 28513847
TI  - Transmission characteristics of a two dimensional antiscatter grid prototype for
      CBCT.
AB  - AIM: High fraction of scattered radiation in cone-beam CT (CBCT) imaging degrades
      CT number accuracy and visualization of low contrast objects. To suppress scatter
      in CBCT projections, we developed a focused, two-dimensional antiscatter grid
      (2DASG) prototype. In this work, we report on the primary and scatter
      transmission characteristics of the 2DASG prototype aimed for linac mounted,
      offset detector geometry CBCT systems in radiation therapy, and compared its
      performance to a conventional one-dimensional ASG (1DASG). METHODS: The 2DASG is
      an array of through-holes separated by 0.1 mm septa that was fabricated from
      tungsten using additive manufacturing techniques. Through-holes' focusing
      geometry was designed for offset detector CBCT in Varian TrueBeam system. Two
      types of ASGs were evaluated: (a) a conventional 1DASG with a grid ratio of 10,
      (b) the 2DASG prototype with a grid ratio of 8.2. To assess the scatter
      suppression performance of both ASGs, Scatter-to-primary ratio (SPR) and scatter
      transmission fraction (Ts) were measured using the beam stop method. Scatter and
      primary intensities were modulated by varying the phantom thickness between 10
      and 40 cm. Additionally, the effect of air gap and bow tie (BT) filter on SPR and
      Ts were evaluated. Average primary transmission fraction (TP ) and pixel specific
      primary transmission were also measured for both ASGs. To assess the effect of
      transmission characteristics on projection image signal-to-noise ratio (SNR), SNR
      improvement factor was calculated. Improvement in contrast to noise ratio (CNR)
      was demonstrated using a low contrast object. RESULTS: In comparison to 1DASG,
      2DASG reduced SPRs by a factor of 3 to 6 across the range of phantom setups
      investigated. Ts values for 1D and 2DASGs were in the range of 21 to 29%, and 5
      to 14% respectively. 2DASG continued to provide lower SPR and Ts at increased air
      gap and with BT filter. Tp of 1D and 2DASGs were 70.6% and 84.7% respectively.
      Due to the septal shadow of the 2DASG, its pixel specific primary transmission
      values varied between 32.5% and 99.1%. With respect to 1DASG, 2DASG provided up
      to factor of 1.7 more improvement in SNR across the SPR range investigated.
      Moreover, 2DASG provided improved visualization of low contrast objects with
      respect to 1DASG and NOASG setups. CONCLUSIONS: When compared to a conventional
      1DASG, 2DASG prototype provided noticeably lower SPR and Ts values, indicating
      its superior scatter suppression performance. 2DASG also provided 19% higher
      average primary transmission that was attributed to the absence of interseptal
      spacers and optimized grid geometry. Our results indicate that the combined
      effect of lower scatter and higher primary transmission provided by 2DASG may
      potentially translate into more accurate CT numbers and improved contrast
      resolution in CBCT images.

PMID- 28513849
TI  - Surgical considerations for papillary thyroid microcarcinomas.
AB  - We reevaluate current treatment recommendations of papillary thyroid
      microcarcinomas taking into account the indolent behavior of these tumors, and
      the potential morbidity that may result from an unnecessary surgery. The goals of
      this communication are to: 1) provide surgeons and endocrinologists with the most
      up-to-date evidence on management of microcarcinomas, 2) outline appropriate
      instances for active surveillance, and 3) describe the role of surgical
      interventions for microcarcinomas including lobectomy, total thyroidectomy, and
      central neck dissection.

PMID- 28513850
TI  - Small prey species' behaviour and welfare: implications for veterinary
      professionals.
AB  - People have obligations to ensure the welfare of animals under their care.
      Offences under the UK Animal Welfare Act are acts, or failures of action, causing
      unnecessary suffering. Veterinary professionals need to be able to provide
      current, scientifically based prophylactic advice, and respect the limits of
      their expertise. The ethical concept of a life worth living and the Five Freedoms
      are core to welfare. Behaviour is a central component, both influencing and
      influenced by physical health. Owners frequently misunderstand the behaviour of
      small prey mammals and how to meet their needs. This review provides insight into
      the physical-social (external) and the cognitive-emotional (internal)
      environments of small prey mammals, contextualised within an evolutionary
      perspective. This is extrapolated to captivity and practical suggestions given
      for meeting behavioural freedoms and enhancing client understanding and enjoyment
      of their animals, thereby improving welfare.

PMID- 28513851
TI  - Population Pharmacokinetics of Brentuximab Vedotin in Patients With CD30
      Expressing Hematologic Malignancies.
AB  - Brentuximab vedotin, a CD30-directed antibody-drug conjugate (ADC), is approved
      for treating certain patients with CD30-expressing hematologic malignancies. Its
      primary mechanism of action is the targeted delivery of a microtubule-disrupting
      agent, monomethyl auristatin E (MMAE), to CD30-expressing cells. A population
      pharmacokinetic (PopPK) analysis was conducted to characterize the PK of ADC and
      unconjugated MMAE in patients with CD30-expressing hematologic malignancies by
      compartmental analysis and to evaluate the effects of covariates on PK of the
      ADC. A nonlinear mixed-effects modeling approach was used to evaluate data from
      314 patients in 5 clinical studies. ADC PK was described by a linear, 3
      compartment model with first-order elimination. MMAE PK was described by a
      semimechanistic, linear, 2-compartment model with first-order elimination. The
      estimated typical values for a 75-kg male patient were 1.56 L/d and 4.29 L for
      ADC systemic clearance (CL) and volume of central compartment (V1), respectively,
      with weight effect exponents of 0.698 and 0.503, respectively. Typical V1 in 75
      kg females was 87% of that in males, with no impact on systemic ADC exposure.
      Typical values of MMAE clearance (CLM ) and volume of central compartment (V4)
      were 55.7 L/d and 79.8 L, respectively, with weight effect exponents fixed to
      0.75 and 1.0, respectively. This is the first PopPK model of brentuximab vedotin
      to semimechanistically link the PK of ADC and that of the unconjugated small
      molecule MMAE. Both ADC and MMAE PK data were adequately described by the final
      integrated model, which supports weight-based dosing of brentuximab vedotin in
      adult patients with CD30-expressing hematologic malignancies.

PMID- 28513852
TI  - Effect of Pentoxifylline in Ameliorating Myocardial Injury in Patients With
      Myocardial Infarction Undergoing Thrombolytic Therapy: A Pilot Randomized
      Clinical Trial.
AB  - Cell death following acute myocardial infarction (MI) is the hallmark pathology
      of cardiovascular disease, leading to considerable mortality and morbidity.
      Platelet and neutrophil activation and inflammatory cytokines, prominently TNF
      alpha, play an important role in the development of cell death. Because
      pentoxifylline inhibits platelet and neutrophil activation and reduces TNF-alpha,
      this study was performed to assess the potential benefit of pentoxifylline in the
      reduction of myocardial injury following acute MI. In this randomized clinical
      trial, 98 patients with acute MI were randomly divided into 2 groups. The
      intervention group received an oral dose of 1200 mg of pentoxifylline immediately
      before thrombolytic therapy (TLT). All patients received the same standard
      protocol for treatment of MI. Cardiac enzymes were checked over 48 hours. ST
      resolution was measured over 90 minutes. Then all patients were followed up for a
      1-month period to assess major adverse cardiac effects (MACEs). There were no
      significant differences in peak levels of CPK (P = .18) and CK-MB (P = .33)
      between the 2 groups, whereas peak level of troponin I was significantly lower in
      the pentoxifylline group (16.8 +/- 10.4 vs 21.3 +/- 11.6; P = .048). No
      significant change between the groups was observed in biomarkers levels, ST
      segment resolution, cardiac ejection fraction, and MACEs. The results showed that
      pentoxifylline significantly reduced the peak value of troponin I in patients
      with acute MI receiving TLT. No significant change was observed in the other
      studied parameters. Further outcome-based studies are needed to show the clinical
      relevance of differences between the groups in troponin peak.

PMID- 28513853
TI  - Association between textural and morphological tumor indices on baseline PET-CT
      and early metabolic response on interim PET-CT in bulky malignant lymphomas.
AB  - PURPOSE: We investigated whether metabolic, textural, and morphological tumoral
      indices evaluated on baseline PET-CT were predictive of early metabolic response
      on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin
      malignant lymphomas. METHODS: This retrospective study included 57 patients
      referred for initial PET-CT examination. In-house dedicated software was used to
      delineate tumor contours using a fixed 30% threshold of SUV max and then to
      compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation,
      skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis,
      and area under the curve of the cumulative histogram), textural parameters
      (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from
      the gray-level co-occurrence matrix, area under the curve of the power spectral
      density, auto-correlation distance, and granularity), and shape parameters
      (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal
      dimensions). Early metabolic response was assessed on interim PET-CT using the
      Deauville 5-point scale and patients were ranked according to the Lugano
      classification as complete or not complete metabolic responders. The impact of
      the segmentation method (alternate threshold at 41%) and image resolution
      (Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of
      the proposed parameters with early response was assessed in univariate and
      multivariate analyses. Their added predictive value was explored using supervised
      classification by support vector machines (SVM). We evaluated in leave-one-out
      cross-validation three SVMs admitting as input features (a) MTV, (b) MTV +
      histological type, and (c) MTV + histology + relevant texture/shape indices.
      RESULTS: Features associated with complete metabolic response were low MTV (P =
      0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high
      surfacic extension (P = 0.006), low 2D fractal dimension (P = 0.007), and low 3D
      fractal dimension (P = 0.003). The prognostic value of these metrics was optimal
      with the 30% segmentation threshold and overall was progressively altered with
      decreasing image resolution. In cross-validation, the SVM accounting for texture
      and shape achieved the highest predictive value with ROC AUC of 0.82 and 80%
      accuracy (compared with 0.68 and 61% for MTV, and 0.65 and 68% for MTV +
      histology). CONCLUSIONS: The combination of usual prognostic factors with
      appropriately chosen textural and shape parameters evaluated on baseline PET-CT
      improves the prediction of early metabolic response in bulky lymphoma.

PMID- 28513854
TI  - Verification of dose profiles generated by the convolution algorithm of the gamma
      knife(r) radiosurgery planning system.
AB  - PURPOSE: A convolution algorithm that takes into account electron-density
      inhomogeneity was recently introduced to calculate dose distributions for the
      Gamma Knife (GK) PerfexionTM treatment planning program. The accuracies of the
      dose distributions computed using the convolution method were assessed using an
      anthropomorphic phantom and film dosimetry. METHODS: Absorbed-dose distributions
      inside a phantom (CIRS Radiosurgery Head Phantom, Model 605) were calculated
      using the convolution method of the GK treatment-planning software (Leksell Gamma
      Plan(r) version 10.1; LGP) for various combinations of collimator size, location,
      direction of calculation plane, and number of shots. Computed tomography (CT)
      images of the phantom and a data set of CT number versus electron density were
      provided to the LGP. Calculated distributions were exported as digital-image
      communications in medicine-radiation therapy (DICOM-RT) files. Three types of
      radiochromic film (GafChromic(r) MD-V2-55, MD-V3, and EBT2) were irradiated
      inside the phantom using GK PerfexionTM. Scanned images of the measured films
      were processed following standard radiochromic film-handling procedures. For a
      two-dimensional quantitative evaluation, gamma index pass rates (GIPRs) and
      normalized agreement-test indices (NATIs) were obtained. Image handling and index
      calculations were performed using a commercial software package (DoseLab Pro
      version 6.80). RESULTS: The film-dose calibration data were well fitted with
      third-order polynomials (R2  >= 0.9993). The mean GIPR and NATI of the 93
      analyzed films were 99.3 +/- 1.1% and 0.8 +/- 1.3, respectively, using 3%/1.0 mm
      criteria. The calculated maximum doses were 4.3 +/- 1.7% higher than the measured
      values for the 4 mm single shots and 1.8 +/- 0.7% greater than those for the 8 mm
      single shots, whereas differences of only 0.3 +/- 0.9% were observed for the 16
      mm single shots. The accuracy of the calculated distribution was not
      statistically related to the collimator size, number of shots, or centrality of
      location (P > 0.05, independent-sample t-test). The plans in the axial planes
      exhibited poorer agreement with the measured distributions than the plans in the
      coronal or sagittal planes; however, their GIPR values (>= 96.9%) were clinically
      acceptable. The plans for an arbitrary virtual target of volume 1.6 cm3 at an
      axial plane close to the top of the phantom showed the worst agreement and the
      greatest fluctuation (GIPR = 96.9 +/- 1.2%, NATI = 3.9 +/- 1.7). CONCLUSIONS: The
      measured accuracies of the dose distributions calculated by the convolution
      algorithm of the LGP were within the clinically acceptable range (GIPR >= 96.9%)
      for various configurations of collimator size, location, direction of calculation
      plane, and number of shots. Due to the intrinsic asymmetry in the dose
      distribution along the z-axis, the treatment plan should also be verified in
      coronal or sagittal plane.

PMID- 28513855
TI  - Technical Note: System for evaluating local hypothermia as a radioprotector of
      the rectum in a small animal model.
AB  - PURPOSE: The protective effects of induced or even accidental hypothermia on the
      human body are widespread with several medical uses currently under active
      research. In vitro experiments using human cell lines have shown hypothermia
      provides a radioprotective effect that becomes more pronounced at large, single
      fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic
      radiosurgery (SRS) treatments. This work describes the development of a system to
      evaluate local hypothermia for a radioprotective effect of the rat rectum during
      a large dose of radiation relevant to prostate SBRT. This includes the evaluation
      of a 3D-printed small animal rectal cooling device and the integration with a
      small animal irradiator. METHODS: A 3-cm long, dual-lumen rectal temperature
      control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA
      was capable of recirculating flow in a device small enough for insertion into the
      rat rectum, with a metal support rod for strength as well as visibility during
      radiation treatment planning. The outer walls of the RTCA comprised of thin heat
      shrink plastic, achieving efficient heat transfer into adjacent tissues.
      Following leak-proof testing, fiber optic temperature probes were used to
      evaluate the temperature over time when placed adjacent to the cooling device
      within the rat rectum. MRI thermometry characterized the relative temperature
      distribution in concentric ROIs surrounding the probe. Integration with an image
      guided small animal irradiator and associated treatment planning system included
      evaluation for imaging artifacts and effect of brass tubing on dose calculation.
      RESULTS: The rectal temperature adjacent to the cooling device decreased from
      body temperature to 15 degrees C within 10-20 min from device insertion and was
      maintained at 15 +/- 3 degrees C during active cooling for the evaluated time of
      one hour. MR thermometry revealed a steep temperature gradient with increasing
      distance from the cooling device with the desired temperature range maintained
      within the surrounding few millimeters. CONCLUSIONS: A 3D-printed rectal cooling
      device was fabricated for the purpose of inducing local hypothermia in the rat
      rectum. The RTCA was simply integrated with an image-guided small animal
      irradiator and Monte Carlo-based treatment planning system to facilitate an in
      vivo investigation of the radioprotective effect of hypothermia for late rectal
      toxicity following a single large dose of radiation.

PMID- 28513856
TI  - The Utility of a Population Approach in Drug-Drug Interaction Assessments: A
      Simulation Evaluation.
AB  - This study aims at evaluating the utility of the population pharmacokinetics
      approach in therapeutic protein drug-drug-interaction (DDI) assessment.
      Simulations were conducted for 2 representative victim drugs, methotrexate and
      trastuzumab, using a parallel-group design with and without the interaction drug.
      The effect of a perpetrator on the exposure of the victim drug is described as
      the ratio of clearance/apparent clearance of the victim drug given with or
      without the perpetrator. The power of DDI assessment was calculated as the
      percentage of runs with 90% confidence interval of the estimated DDI effect
      within 80% to 125% for the scenarios of no DDI, benchmarked with the
      noncompartmental approach with intensive sampling. The impact of the number of
      subjects, the number of sampling points per subject, sampling time error, and
      model misspecification on the power of DDI determination were evaluated. Results
      showed that with equal numbers of subjects in each arm, the population
      pharmacokinetics approach with sparse sampling may need about the same or a
      higher number of subjects compared to a noncompartmental approach in order to
      achieve similar power. Increasing the number of subjects, even if only in the
      study drug alone arm, can increase the power. Sampling or dosing time error had
      notable impacts on the power for methotrexate but not for trastuzumab. Model
      misspecification had no notable impacts on the power for trastuzumab. Overall,
      the population pharmacokinetics approach with sparse sampling built in phase 2/3
      studies allows appropriate DDI assessment with adequate study design and analysis
      and can be considered as an alternative to dedicated DDI studies.

PMID- 28513857
TI  - Angiogenesis during pregnancy: all routes lead to MAPKs.

PMID- 28513858
TI  - An adaptive Fuzzy C-means method utilizing neighboring information for breast
      tumor segmentation in ultrasound images.
AB  - PURPOSE: Ultrasound (US) imaging has been widely used in breast tumor diagnosis
      and treatment intervention. Automatic delineation of the tumor is a crucial first
      step, especially for the computer-aided diagnosis (CAD) and US-guided breast
      procedure. However, the intrinsic properties of US images such as low contrast
      and blurry boundaries pose challenges to the automatic segmentation of the breast
      tumor. Therefore, the purpose of this study is to propose a segmentation
      algorithm that can contour the breast tumor in US images. METHODS: To utilize the
      neighbor information of each pixel, a Hausdorff distance based fuzzy c-means
      (FCM) method was adopted. The size of the neighbor region was adaptively updated
      by comparing the mutual information between them. The objective function of the
      clustering process was updated by a combination of Euclid distance and the
      adaptively calculated Hausdorff distance. Segmentation results were evaluated by
      comparing with three experts' manual segmentations. The results were also
      compared with a kernel-induced distance based FCM with spatial constraints, the
      method without adaptive region selection, and conventional FCM. RESULTS: Results
      from segmenting 30 patient images showed the adaptive method had a value of
      sensitivity, specificity, Jaccard similarity, and Dice coefficient of 93.60 +/-
      5.33%, 97.83 +/- 2.17%, 86.38 +/- 5.80%, and 92.58 +/- 3.68%, respectively. The
      region-based metrics of average symmetric surface distance (ASSD), root mean
      square symmetric distance (RMSD), and maximum symmetric surface distance (MSSD)
      were 0.03 +/- 0.04 mm, 0.04 +/- 0.03 mm, and 1.18 +/- 1.01 mm, respectively. All
      the metrics except sensitivity were better than that of the non-adaptive
      algorithm and the conventional FCM. Only three region-based metrics were better
      than that of the kernel-induced distance based FCM with spatial constraints.
      CONCLUSION: Inclusion of the pixel neighbor information adaptively in segmenting
      US images improved the segmentation performance. The results demonstrate the
      potential application of the method in breast tumor CAD and other US-guided
      procedures.

PMID- 28513859
TI  - Identification of a plasma miRNA biomarker signature for allergic asthma: A
      translational approach.
AB  - BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes
      and treatment responses. Thus, there is a high clinical need for molecular
      disease biomarkers to aid in differentiating these distinct phenotypes. As
      MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional
      level, are altered in experimental and human asthma, circulating miRNAs are
      attractive candidates for the identification of novel biomarkers. This study
      aimed to identify plasmatic miRNA-based biomarkers of asthma, through a
      translational approach. METHODS: We prescreened miRNAs in plasma samples from two
      different murine models of experimental asthma (ovalbumin and house dust mite);
      miRNAs deregulated in both models were further tested in a human training cohort
      of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then
      validated in a second, independent group of 26 asthma patients and 12 healthy
      controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially
      regulated in both murine models. Measuring these miRNAs in the training cohort
      identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This
      signature showed a good sensitivity and specificity in the test cohort with an
      area under the receiver operating characteristic curve (AUC) of 0.92. Correlation
      of miRNA ratios with clinical characteristics further revealed associations with
      FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION:
      Distinct plasma miRNAs are differentially regulated both in murine and in human
      allergic asthma and were associated with clinical characteristics of patients.
      Thus, we suggest that miRNA levels in plasma might have future potential to
      subphenotype patients with asthma.

PMID- 28513861
TI  - Regulatory and Ethical Issues in Pediatric Clinical Research: Recommendations
      From a Panel Discussion.

PMID- 28513860
TI  - Cortical contributions to sensory gating in the ipsilateral somatosensory cortex
      during voluntary activity.
AB  - KEY POINTS: It has long been known that the somatosensory cortex gates sensory
      inputs from the contralateral side of the body. Here, we examined the
      contribution of the ipsilateral somatosensory cortex (iS1) to sensory gating
      during index finger voluntary activity. The amplitude of the P25/N33, but not
      other somatosensory evoked potential (SSEP) components, was reduced during
      voluntary activity compared with rest. Interhemispheric inhibition between S1s
      and intracortical inhibition in the S1 modulated the amplitude of the P25/N33.
      Note that changes in interhemispheric inhibition between S1s correlated with
      changes in cortical circuits in the ipsilateral motor cortex. Our findings
      suggest that cortical circuits, probably from somatosensory and motor cortex,
      contribute to sensory gating in the iS1 during voluntary activity in humans.
      ABSTRACT: An important principle in the organization of the somatosensory cortex
      is that it processes afferent information from the contralateral side of the
      body. The role of the ipsilateral somatosensory cortex (iS1) in sensory gating in
      humans remains largely unknown. Using electroencephalographic (EEG) recordings
      over the iS1 and electrical stimulation of the ulnar nerve at the wrist, we
      examined somatosensory evoked potentials (SSEPs; P14/N20, N20/P25 and P25/N33
      components) and paired-pulse SSEPs between S1s (interhemispheric inhibition) and
      within (intracortical inhibition) the iS1 at rest and during tonic index finger
      voluntary activity. We found that the amplitude of the P25/N33, but not other
      SSEP components, was reduced during voluntary activity compared with rest.
      Interhemispheric inhibition increased the amplitude of the P25/N33 and
      intracortical inhibition reduced the amplitude of the P25/N33, suggesting a
      cortical origin for this effect. The P25/N33 receives inputs from the motor
      cortex, so we also examined the contribution of distinct sets of cortical
      interneurons by testing the effect of ulnar nerve stimulation on motor-evoked
      potentials (MEPs) elicited by transcranial magnetic stimulation over the
      ipsilateral motor cortex with the coil in the posterior-anterior (PA) and
      anterior-posterior (AP) orientation. Afferent input attenuated PA, but not AP,
      MEPs during voluntary activity compared with rest. Notably, changes in
      interhemispheric inhibition correlated with changes in PA MEPs. Our novel
      findings suggest that interhemispheric projections between S1s and intracortical
      circuits, probably from somatosensory and motor cortex, contribute to sensory
      gating in the iS1 during voluntary activity in humans.

PMID- 28513862
TI  - Liver transplantation for unresectable colorectal liver metastases: A systematic
      review.
AB  - The use of liver transplantation (LT) for liver metastases attempted in the early
      1990's was associated with poor perioperative outcomes and unacceptably low
      overall survival. Recently, there has been renewed interest in LT as a treatment
      option for colorectal liver metastases (CLM) in countries where organ supply is
      high. To date, no meticulous analysis about the efficacy, safety and outcomes of
      LT in CLM patients has been published. We present the first systematic review on
      the subject.

PMID- 28513863
TI  - Relative contributions of maternal Western-type high fat, high sugar diets and
      maternal obesity to altered metabolic function in pregnancy.

PMID- 28513864
TI  - The influence of non-rigid anatomy and patient positioning on endoscopy-CT image
      registration in the head and neck.
AB  - PURPOSE: To assess the influence of non-rigid anatomy and differences in patient
      positioning between CT acquisition and endoscopic examination on endoscopy-CT
      image registration in the head and neck. METHODS: Radiotherapy planning CTs and
      31-35 daily treatment-room CTs were acquired for nineteen patients. Diagnostic
      CTs were acquired for thirteen of the patients. The surfaces of the airways were
      segmented on all scans and triangular meshes were created to render virtual
      endoscopic images with a calibrated pinhole model of an endoscope. The virtual
      images were used to take projective measurements throughout the meshes, with
      reference measurements defined as those taken on the planning CTs and test
      measurements defined as those taken on the daily or diagnostic CTs. The influence
      of non-rigid anatomy was quantified by 3D distance errors between reference and
      test measurements on the daily CTs, and the influence of patient positioning was
      quantified by 3D distance errors between reference and test measurements on the
      diagnostic CTs. The daily CT measurements were also used to investigate the
      influences of camera-to-surface distance, surface angle, and the interval of time
      between scans. RESULTS: Average errors in the daily CTs were 0.36 +/- 0.61 cm in
      the nasal cavity, 0.58 +/- 0.83 cm in the naso- and oropharynx, and 0.47 +/- 0.73
      cm in the hypopharynx and larynx. Average errors in the diagnostic CTs in those
      regions were 0.52 +/- 0.69 cm, 0.65 +/- 0.84 cm, and 0.69 +/- 0.90 cm,
      respectively. All CTs had errors heavily skewed towards 0, albeit with large
      outliers. Large camera-to-surface distances were found to increase the errors,
      but the angle at which the camera viewed the surface had no effect. The errors in
      the Day 1 and Day 15 CTs were found to be significantly smaller than those in the
      Day 30 CTs (P < 0.05). CONCLUSIONS: Inconsistencies of patient positioning have a
      larger influence than non-rigid anatomy on projective measurement errors. In
      general, these errors are largest when the camera is in the superior pharynx,
      where it sees large distances and a lot of muscle motion. The errors are larger
      when the interval of time between CT acquisitions is longer, which suggests that
      the interval of time between the CT acquisition and the endoscopic examination
      should be kept short. The median errors found in this study are comparable to
      acceptable levels of uncertainty in deformable CT registration. Large errors are
      possible even when image alignment is very good, indicating that projective
      measurements must be made carefully to avoid these outliers.

PMID- 28513865
TI  - Diagnosis of Tuberculosis in HIV Co-infected Individuals: Current Status,
      Challenges and Opportunities for the Future.
AB  - Tuberculosis (TB) remains one of the most important causes of death among people
      co-infected with human immunodeficiency virus (HIV). The diagnosis of TB remains
      challenging in HIV co-infected individuals, due to a high frequency of smear
      negative disease and high rates of extrapulmonary TB. Accurate, ease of use and
      rapid diagnosis of active TB are critical to the World Health Organization (WHO)
      End TB Strategy by 2050. Traditional laboratory techniques do not provide rapid
      and accurate results to effectively manage HIV co-infected patients. Over the
      last decade, molecular methods have provided significant steps in the fight
      against TB. However, many HIV co-infected patients do not have access to these
      molecular diagnostic tests. Given the costs closely related with confirming a TB
      diagnosis in HIV patients, an overtreatment for TB is used in this patient
      population. Nowadays, an estimated US $8 billion a year is required to provide TB
      treatment, which is very high compared with making an important strategy to
      improve the current diagnostic tests. This review focuses on current advances in
      diagnosing active TB with an emphasis on the diagnosis of HIV-associated TB. Also
      discussed are the main challenges that need to be overcome for improving an
      adequate initial diagnosis of active TB in HIV-positive patients.

PMID- 28513866
TI  - LncRNA PTCSC3/miR-574-5p Governs Cell Proliferation and Migration of Papillary
      Thyroid Carcinoma via Wnt/beta-Catenin Signaling.
AB  - The distance metastases of papillary thyroid carcinoma (PTC) were a major
      threaten for PTC patients, thus, to study the potential mechanism for the
      treatment of PTC was essential. Previous studies have shown that PTCSC3 (Thyroid
      Carcinoma Susceptibility Candidate 3), miR-574-5p and Wnt/beta-catenin were
      involved in PTC, but the potential pathogenic mechanism among them was still
      unclear. Real-time PCR and Western blot were used to detect genes expression.
      Luciferase reporter assay was used to detect the combination of miR-574-5p and
      suppressor of cancer cell invasion (SCAI), as well as the ratio of TOP/FOP. RNA
      Pull-down assay verified the bound of PTCSC3 and miR-574-5p. MTT assay, Transwell
      assay, and wound scratch assay were used to detect cell viability and cell
      migration. The expression of PTCSC3 and SCAI were decreased, while miR-574-5p and
      beta-catenin were increased in PTC tissues and cells. Overexpressed PTCSC3
      suppressed cell proliferation and migration, promoted the expression of SCAI, but
      inhibited beta-catenin. PTCSC3 absorbed miR-574-5p, and miR-574-5p targeted to
      SCAI; SCAI could regulate the activity of Wnt/beta-catenin. PTCSC3/miR-574-5p
      regulated the activity of Wnt/beta-catenin via SCAI and mediated cell
      proliferation and migration of PTC-1. In vivo experiments verified the fact that
      overexpressed PTCSC3 inhibited tumor growth. The signaling PTCSC3-miR-574-5p-SCAI
      Wnt/beta-catenin mediated the proliferation and migration of PTC-1 cells, which
      was vital for the further PTC therapy and prognosis. J. Cell. Biochem. 118: 4745
      4752, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513867
TI  - The Role of Circulating T Follicular Helper Cells and Regulatory Cells in Non
      Small Cell Lung Cancer Patients.
AB  - T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells are
      identified as the new subset of immune cells. This study aims to investigate the
      role of circulating Tfh cells (cTfh) and Tfr (cTfr) cells in the pathogenesis of
      non-small cell lung cancer (NSCLC). A total of 27 NSCLC patients and 19 age and
      sex-matched healthy controls were enrolled. The percentage of cTfh and cTfr was
      detected by flow cytometric analysis. Compared to healthy controls, a
      significantly higher percentage of both cTfh and cTfr cells were observed in
      NSCLC patients (for cTfh, 18.88% +/- 16.84% versus 5.98% +/- 3.70%, P < 0.01; for
      cTfr, 2.67% +/- 2.20% versus 1.14% +/- 0.76%, P < 0.01). Furthermore, there was a
      positive correlation between cTfh/cTfr ratio and age in NSCLC patients (P <
      0.05). When taking age 60 as a cut-off, the percentage of both cTfh cells and
      cTfr cells were higher in older patients than younger patients. Moreover, our
      data showed there was lower percentage of cTfh cells in NSCLC patients with early
      stage disease (I and II) (12.10% +/- 12.22%) than that in advanced stage disease
      (III and IV) (30.41% +/- 17.87%) (P < 0.01). However, no significant relationship
      was observed between cTfr cells and clinical stage in NSCLC patients. A higher
      percentage of cTfh cells was observed in patients with squamous cell carcinoma
      compared with adenocarcinoma (31.70% +/- 20.73% versus. 13.48% +/- 11.78%, P <
      0.05). Taken together, there was significantly higher percentage of cTfh and cTfr
      cells in NSCLC patients. cTfh and cTfr cells might play an important role in the
      pathogenesis of NSCLC patients.

PMID- 28513868
TI  - HER2 assessment in locally advanced gastric cancer: comparing the results
      obtained with the use of two primary tumour blocks versus those obtained with the
      use of all primary tumour blocks.
AB  - AIMS: HER2 is currently the only biomarker used to select eligible patients with
      advanced gastric cancer (GC) for targeted therapy. The aims of this study were to
      verify the value of dual-block HER2 assessment and to explore whether increasing
      the block number is more beneficial by carrying out a randomized prospective
      cohort study in which dual-block and all-block HER2 assessment were compared in
      resected specimens of GC. METHODS AND RESULTS: Five hundred and forty-nine
      resected GC specimens were randomly enrolled into two cohorts: a dual-block group
      (n = 274) with two primary tumour blocks tested, and an all-block group (n = 275)
      with all primary tumour blocks tested. Immunohistochemical staining of HER2 was
      performed. For HER2-equivocal (2+) cases, fluorescence in-situ hybridization
      (FISH) was performed. As compared with single-block assessment, dual-block
      assessment increased the HER2 immunohistochemistry (IHC)-positive (3+) rate. The
      rate with dual-block assessment (11.3%) was significantly higher than that with
      block 1 assessment (8.8%) (P = 0.016) and block 2 assessment (9.1%) (P = 0.031).
      Similarly, all-block assessment demonstrated a higher HER2 3+ rate (12.4%) than
      single-block assessment (block 1, 6.5%; block 2, 6.2%; block 3, 7.2%; block 4,
      8.7%) (P < 0.05). HER2 3+ rates of all-block and dual-block assessments showed no
      significant difference (P = 0.703). After IHC and FISH results had been combined,
      the HER2-positive rate with all-block assessment (13.5%) was slightly higher than
      that with dual-block assessment (12.0%), although the difference was not
      statistically significant (P = 0.62). CONCLUSIONS: Dual-block immunohistochemical
      assessment is an effective, practical and economic approach that is suitable for
      the preliminary screening of HER2. We recommend that dual-block HER2 assessment
      be routinely performed on resected specimens of GC. All-block assessment can be a
      supplement to dual-block assessment if necessary.

PMID- 28513869
TI  - Transition of Intravenous Treprostinil to Oral Therapy in a Patient with
      Functional Class IV Chronic Thromboembolic Pulmonary Hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary
      emboli fail to resolve with anticoagulation. For patients with inoperable or
      residual CTEPH, riociguat is currently the only therapy approved by the United
      States Food and Drug Administration. However, some patients with CTEPH may
      require therapy beyond riociguat, such as intravenous prostacyclins, which can
      present significant administration challenges in patients with complex comorbid
      conditions. We describe a 42-year-old man with T12 paraplegia complicated by
      CTEPH (functional class IV with substantial right ventricular dysfunction) and
      severe pressure ulcers. In order to facilitate goals of care (hospital discharge
      to a skilled nursing facility where parenteral prostanoids could not be
      administered), he underwent rapid transition from intravenous treprostinil to
      oral selexipag in the form of a cross-taper over 6 days. The patient required
      readmission due to worsening symptoms and was transitioned back to intravenous
      treprostinil; he tolerated conversion to oral treprostinil for approximately 4
      months, but it was subsequently discontinued due to nausea and modified goals of
      care. The patient underwent transition to hospice care 3 months later and
      eventually died from clinical deterioration. To our knowledge, this is the first
      report to describe transition from intravenous treprostinil to selexipag as well
      as conversion from parenteral treprostinil to oral treprostinil in a patient with
      CTEPH and illustrates the approaches to and potential issues with prostanoid
      transitions. Additional observations are necessary to better understand the
      relative roles of selexipag and oral treprostinil regarding comparative efficacy
      and tolerability.

PMID- 28513870
TI  - Activation of the Nrf2-ARE Signaling Pathway Prevents Hyperphosphatemia-Induced
      Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle
      Cells.
AB  - This study investigates the effect of nuclear factor erythroid 2-related factor 2
      antioxidant response element (Nrf2-ARE) signaling pathway in vascular
      calcification (VC) via inducing Autophagy in renal vascular smooth muscle cells
      (VSMCs). VSMCs were assigned into six experimental groups: the normal control,
      high phosphorus, si-negative control (si-NC), Nrf2-siRNA, over-expressed Nrf2,
      and negative control (NC) groups. RT-PCR was applied to detect the mRNA
      expressions of the desired Nrf2-ARE signaling pathway-related genes (Nrf2, NQO-1,
      HO-1, gamma-GCS). The protein products of these genes: apoptosis-related genes
      (LC3I and LC3II), osteogenic marker proetins (Runt-related transcription factor
      2) Runx2 and BMP2 were all detected by Western blotting. Autophagosomes in VSMCs
      were observed under a transmission electron microscope. We discovered an
      increased calcium ion concentration and upregulated Runx2, BMP2, Nrf2, HO-1,
      gamma-GCS, NQO-1, and LC3II/LC3I expressions in the high phosphorous, si-NC and
      Nrf2-siRNA, and NC groups, compared with the normal control group. Compared to
      the high phosphorus and si-NC groups, higher levels of Runx2 and BMP2 but
      decreased Nrf2, HO-1, gamma-GCS, NQO-1, and LC3II/LC3I expressions were detected
      in the Nrf2-siRNA group. The high phosphorus, si-NC and over-expressed Nrf2
      experimental groups all had increased Nrf2, NQO-1, HO-1, gamma-GCS, and
      LC3II/LC3I expressions as well as high numbers of autophagosomes compared with
      the normal control group. Finally, we detected a lower amount of autophagosomes
      presence and Nrf2, NQO-1, HO-1 gamma-GCS, and LC3II/LC3 protein expression of
      Nrf2-siRNA group than that of the high phosphorus and si-NC groups. Activation of
      Nrf2-ARE signaling pathway may prevent hyperphosphatemia-induced VC by inducing
      autophagy in VSMCs. J. Cell. Biochem. 118: 4708-4715, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28513871
TI  - Potential Role of Long Non-Coding RNA ANRIL in Pediatric Medulloblastoma Through
      Promotion on Proliferation and Migration by Targeting miR-323.
AB  - Medulloblastoma (MB) is a common primary tumor of the central nervous system
      diagnosed in pediatric patients. Survivors of MB are frequently accompanied by
      severe side effects, thus it is urgent to explore novel therapeutic target. First
      of all, the level of antisense non-coding RNA in the INK4 locus (ANRIL) in normal
      cerebellum and DAOY cells were evaluated. Then, the effect of ANRIL on DAOY cell
      proliferation, migration, and apoptosis were tested. Then, qRT-PCR was performed
      to explore whether ANRIL acted as a sponge of miR-323. The effects of miR-323
      inhibition on ANRIL silence-induced alterations of cell proliferation, migration,
      and apoptosis were estimated. Predicted by TargetScan, the possible target gene
      of miR-323 was screened, followed by validation with luciferase assay. The
      abnormally expressed BRI3 on cell proliferation, migration, apoptosis, and
      signaling pathways were all evaluated. ANRIL was up-regulated in MB and its
      silence significantly lowered cell viability and migration but promoted cell
      apoptosis. ANRIL acted as a sponge of miR-323 and its silence functioned through
      up-regulating miR-323. BRI3 and CDK6 were target genes of miR-323 and the effect
      of BRI3 on DAOY cells was the same as ANRIL. Moreover, ANRIL suppression could
      reduce phosphorylated levels of p38 MAPK, ERK and AKT, and inhibit Wnt signaling
      pathway through positively regulating BRI3. ANRIL inhibition repressed cell
      proliferation and migration but promoted cell apoptosis through miR-323-mediated
      regulation of BRI3, which could activate p38 MAPK, ERK, and AKT as well as Wnt
      signaling pathway. J. Cell. Biochem. 118: 4735-4744, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28513872
TI  - Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via
      Antioxidant PRDX6.
AB  - Reactive oxygen species (ROS) play both deleterious and beneficial roles in
      cancer cells. Nucleophosmin (NPM) is heavily implicated in cancers of diverse
      origins, being its gene over-expression in solid tumors or frequent mutations in
      hematological malignancies. However, the role and regulatory mechanism of NPM in
      oxidative stress are unclear. Here, we found that NPM regulated the expression of
      peroxiredoxin 6 (PRDX6), a member of thiol-specific antioxidant protein family,
      consequently affected the level and distribution of ROS. Our data indicated that
      NPM knockdown caused the increase of ROS and its relocation from cytoplasm to
      nucleoplasm. In contrast, overexpression or cytoplasmic localization of NPM
      upregulated PRDX6, and decreased ROS. In addition, NPM knockdown decreased
      peroxiredoxin family proteins, including PRDX1, PRDX4, and PRDX6. Co
      immunoprecipitation further confirmed the interaction between PRDX6 and NPM.
      Moreover, NSC348884, an inhibitor specifically targeting NPM oligomerization,
      decreased PRDX6 and significantly upregulated ROS. These observations
      demonstrated that the expression and localization of NPM affected the homeostatic
      balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis
      of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. J.
      Cell. Biochem. 118: 4697-4707, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513874
TI  - beta3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone
      Marrow MSC Niche.
AB  - Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow,
      however, biological features of this niche are still not fully understood. Given
      the interactions of MSCs with endothelial cells in different tissues, bone marrow
      MSC niche may influence the biological features of endothelial progenitor cells
      (EPCs). To understand the role of the sympathetic nervous system in regulation of
      the MSC niche, we examined whether the manipulation of the MSC niche via beta3
      adrenergic signals will affect EPC features. A selective beta3 agonist (BRL37344)
      or a beta3 antagonist (SR59230A) was administered in mice for 2 weeks to
      determine the potential effects of these regimens on the population of CD133+
      stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were
      harvested and expanded from the mice to examine the effect of changes in the MSC
      niche on EPC features. Improved MSC colony forming potency with increased bone
      marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine
      12 [CXCL12]) expression was shown as a result of intensification of the bone
      marrow adrenergic signals through BRL37344 injection. On the other hand, the
      blockage of these signals limited the expression level of SDF-1 and resulted in
      bone marrow enrichment of CD133+ cells. Manipulation of the MSC niche and
      decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more
      colonies with augmented proliferation and differentiation capacity. Overall, our
      results indicate that the beta3-adrenergic signals regulate the MSC niche,
      thereby resulting in modulation of EPC biological features. J. Cell. Biochem.
      118: 4753-4761, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513875
TI  - Incidence, clinicopathological features and fusion transcript landscape of
      translocation renal cell carcinomas.

PMID- 28513873
TI  - Myxoid fibroadenomas differ from conventional fibroadenomas: a hypothesis
      generating study.
AB  - AIMS: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive
      hypocellular myxoid stroma, and occur sporadically or in the context of Carney
      complex, an inheritable condition caused by PRKAR1A-inactivating germline
      mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12
      mutations in the stromal components of the lesions. The aim of this study was to
      investigate the genomic landscape of MFAs and compare it with that of
      conventional FAs. METHODS AND RESULTS: Eleven MFAs from patients without clinical
      and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour
      and matching normal tissue were subjected to massively parallel sequencing using
      the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer
      Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic
      alterations detected by MSK-IMPACT were tested in samples in which the stromal
      and epithelial components were separately laser capture-microdissected.
      Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in
      six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial
      components were separately microdissected, the mutations were found to be
      restricted to the epithelial rather than the stromal component. The sole
      exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon
      histological re-review, this case was reclassified as a breast myxoma, consistent
      with the spectrum of tumous observed in Carney complex patients. In this case,
      the PRKAR1A somatic mutation was restricted to the stromal component. CONCLUSION:
      MFAs lack MED12 mutations, and their stromal components seem not to harbour
      mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome
      analyses of MFAs are required to elucidate their genetic drivers.

PMID- 28513876
TI  - The inter-play between facilitation and context in the promoting action on
      research implementation in health services framework: A qualitative exploratory
      implementation study embedded in a cluster randomized controlled trial to reduce
      restraint in nursing homes.
AB  - AIM: To explore the inter-play between external facilitation and nursing home
      contexts relative to intervention outcomes. BACKGROUND: The Promoting Action on
      Research Implementation in Health Services framework is frequently used to
      theoretically inform implementation and research in nursing and recent reviews
      indicate high face validity for health services. However, the inter-play and
      relationship between framework sub-elements of evidence, context and facilitation
      and the prospective utility in non-English speaking contexts warrant further
      illumination. DESIGN: In an overarching single-blind cluster-randomized
      controlled trial, we applied participatory action research and ethnography from
      August 2011-June 2015 to evaluate a standardized education intervention to reduce
      restraint and agitation in nursing home residents living with dementia. The trial
      results are published elsewhere. METHODS: Prospectively informed by the PARIHS
      framework, a research team and eight facilitators participating in dual roles as
      action researchers designed, implemented, and evaluated the intervention. How
      contextual factors influenced the facilitation processes were explored in focus
      group interviews (1), reflection notes (84) written by the facilitators' after
      each education session, ethnographic field studies (6 homes), and co-analysis
      workshops (5). Directed content analysis was used to analyse data. RESULTS:
      Clinical leaders taking roles of internal facilitator influenced the success of
      implementation, while complex and fluctuating context elements determined whether
      restraint use was reduced- or not. The PARIHS framework was found to be relevant
      in a non-English nursing home setting, albeit some elements merit further
      conceptualization. CONCLUSIONS: Our findings confirm the prospective utility of
      the PARIHS framework for implementation in a non-English context, particularly
      the notion of implementation processes as dynamic and multifaceted.

PMID- 28513877
TI  - Heart rate and outcome in heart failure with reduced ejection fraction:
      Differences between atrial fibrillation and sinus rhythm-A CIBIS II analysis.
AB  - BACKGROUND: Heart rate has been associated with prognosis in patients with heart
      failure with reduced ejection fraction (HFREF) and sinus rhythm; whether this
      also holds true in patients with atrial fibrillation (AF) is unknown. HYPOTHESIS:
      To evaluate cardiac rhythm and baseline heart rate and the influence of outcome
      in patients with HFREF enrolled in the Cardiac Insufficiency Bisoprolol Study II.
      METHODS: In total, 2539 patients were stratified according to their baseline
      heart rhythm (AF or sinus rhythm) and into quartiles of heart rate (<=70 bpm, 71
      78 bpm, 79-90 bpm, and >90 bpm). The primary outcome was all-cause mortality.
      Mean follow-up was 1.3 years. RESULTS: Mean age was 61 years, mean left
      ventricular ejection fraction was 28%, and 80% were male. A total of 521 (21%)
      patients had AF at baseline. The risk associated with all-cause mortality for
      each 5 bpm increase in heart rate in patients with sinus rhythm (hazard ratio
      [HR]: 1.06, 95% confidence interval [CI]: 1.01-1.11, P = 0.012) was significantly
      different from those with AF (HR: 1.00, 95% CI: 0.94-1.07, P = 0.90, P for
      interaction = 0.041). The risk associated with higher heart rate in sinus rhythm
      was primarily attributable to excess risk in the highest quartile (HR: 1.64, 95%
      CI: 1.18-2.30, P = 0.003). Allocation to bisoprolol did not modify the
      interaction between heart rate, rhythm and outcome. CONCLUSIONS: In HFREF
      patients with AF, a higher heart rate is not associated with increased event
      rates in contrast to HFREF patients with sinus rhythm.

PMID- 28513878
TI  - Gene cloning, expression, and characterization of trehalose-6-phosphate synthase
      from Pleurotus ostreatus.
AB  - Trehalose-6-phosphate synthase (TPS; EC2.4.1.15) catalyzes the first step in
      trehalose synthesis, which involves transfer of glucose from uridine diphosphate
      glucose (UDPG) to glucose 6-phosphate (G6P) to form trehalose-6-phosphate. To
      determine the gene and enzymatic characteristics of TPS in Pleurotus ostreatus,
      we cloned and sequenced the cDNA of PoTPS1, which contains a 1665 bp open reading
      frame that encodes a 554-amino acid protein with a predicted molecular weight of
      62.01 kDa. This gene was expressed in Escherichia coli BL21 and then the
      recombinant protein was purified and characterized. Results showed that the
      optimum pH and temperature for the recombinant PoTPS1 were 7.4 and 30  degrees C,
      respectively; the Km value against G6P and UDPG were 0.14 and 0.17 mM,
      respectively, and the Vmax and Kcat values were 91.86 nkat/g and 5.89 s-1 ,
      respectively. Trehalose content was as high as 158.88 mg g-1 dry weight after
      heat treatment at 40  degrees C for 15 h, which was consistent with highest TPS1
      activity at that time point. This result indicated that PoTPS1 was responsible
      for trehalose synthesis in P. ostreatus.

PMID- 28513879
TI  - The Therapeutic Potential of PI3K/Akt/mTOR Inhibitors in Breast Cancer: Rational
      and Progress.
AB  - Breast cancer (BC) is the most commonly diagnosed cancer in women. The
      PI3K/AKT/mTOR pathway is among the most frequently dysregulated pathways in
      patients with BC. The activation of this pathway is associated with increased
      cell growth and clinical outcome, and its overexpression is associated with a
      poor prognosis. It has been proposed that it may be of importance as a potential
      therapeutic target in the treatment of BC. The aim of current review is to
      provide an overview of the potential utility of PI3K/Akt/mTOR inhibitors in
      patients with BC, with particular emphasis on recent preclinical and clinical
      studies. J. Cell. Biochem. 119: 213-222, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513880
TI  - Unstable rocker shoes promote recovery from marathon-induced muscle damage in
      novice runners.
AB  - We recently reported that wearing unstable rocker shoes (Masai Barefoot
      Technology: MBT) may enhance recovery from marathon race-induced fatigue.
      However, this earlier study only utilized a questionnaire. In this study, we
      evaluated MBT utilizing objective physiological measures of recovery from
      marathon-induced muscle damages. Twenty-five university student novice runners
      were divided into two groups. After running a full marathon, one group wore MBT
      shoes (MBT group), and the control group (CON) wore ordinary shoes daily for 1
      week following the race. We measured maximal isometric joint torque, muscle
      hardness (real time tissue elastography of the strain ratio) in the lower limb
      muscles before, immediately after, and 1, 3, and 8 days following the marathon.
      We calculated the magnitude of recovery by observing the difference in each value
      between the first measurement and the latter measurements. Results showed that
      isometric torques in knee flexion recovered at the first day after the race in
      the MBT group while it did not recover even at the eighth day in the CON group.
      Muscle hardness in the gastrocnemius and vastus lateralis showed enhanced
      recovery in the MBT group in comparison with the CON group. Also for muscle
      hardness in the tibialis anterior and biceps femoris, the timing of recovery was
      delayed in the CON group. In conclusion, wearing MBT shoes enhanced recovery in
      lower leg and thigh muscles from muscle damage induced by marathon running.

PMID- 28513883
TI  - Protein Reduction and Dialysis-Free Work-Up through Phosphines Immobilized on a
      Magnetic Support: TCEP-Functionalized Carbon-Coated Cobalt Nanoparticles.
AB  - Tris(2-carboxyethyl)phosphine (TCEP) is an often-used reducing agent in
      biochemistry owing to its selectivity towards disulfide bonds. As TCEP causes
      undesired consecutive side reactions in various analytical methods (e.g., gel
      electrophoresis, protein labeling), it is usually removed by means of dialysis or
      gel filtration. Here, an alternative method of separation is presented, namely
      the immobilization of TCEP on magnetic nanoparticles. This magnetic reagent
      provides a simple and rapid approach to remove the reducing agent after
      successful reduction. A reduction capacity of 70 MUmol per gram of particles was
      achieved by using surface-initiated atom transfer polymerization.

PMID- 28513881
TI  - Base-Modified Nucleic Acids as a Powerful Tool for Synthetic Biology and
      Biotechnology.
AB  - The ability of various nucleoside triphosphate analogues of deoxyguanosine and
      deoxycytidine with 7-deazadeoxyadenosine (A1 ) and 5-chlorodeoxyuridine (T1 ) to
      serve as substrates for Taq DNA polymerase was evaluated. The triphosphate set
      composed of A1 , T1 , and 7-deazadeoxyguanosine with either 5-methyldeoxycytidine
      or 5-fluorodeoxycytidine was successfully employed in the polymerase chain
      reaction (PCR) of 1.5 kb fragments as well as random oligonucleotide libraries.
      Another effective combination of triphosphates for the synthesis of a 1 kb PCR
      product was A1 , T1 , deoxyinosine, and 5-bromodeoxycytidine. In vivo experiments
      using an antibiotic-resistant gene containing the latter set demonstrated that
      the bacterial machinery accepts fully modified sequences as genetic templates.
      Moreover, the ability of the base-modified segments to selectively protect DNA
      from cleavage by restriction endonucleases was shown. This approach can be used
      to regulate the endonuclease cleavage pattern.

PMID- 28513882
TI  - Imaging Nanoscale Morphology of Semiconducting Polymer Films with Photoemission
      Electron Microscopy.
AB  - Photoemission electron microscopy in combination with polarized laser light is
      presented as a tool permitting direct imaging of polymer-chain orientation and
      local degree of order in semicrystalline samples of semiconducting polymers, a
      promising class of materials for future electronics. The key advantages of this
      imaging tool are its nondestructive and fast measurements, straightforward data
      analysis, the low complexity of sample preparation, and the possibility of
      performing measurements on a broad variety of technologically relevant
      substrates. The high spatial resolution of the microscope provides insights into
      the nanoscale morphology, which is relevant for the material's performance in
      electronic devices.

PMID- 28513885
TI  - Biomechanical function of a balloon nucleus pulposus replacement system: A human
      cadaveric spine study.
AB  - With recent advances in motion-sparing techniques in spine surgery, disc nucleus
      replacement (DNR) has been introduced as a viable method to restore the
      biomechanical functions of the spine. Several methods of DNR have been proposed
      in the literature. However, the risk of device migration or extrusion is a major
      issue that should be addressed for a successful DNR. DNR using a balloon nucleus
      (BN) filled with pressurized fluid may be capable of reducing such risks while
      preserving the advantages of DNR. The objective of this study was to investigate
      the biomechanical functionalities of the human cadaveric lumbar motion segments
      with a custom made BN filled with saline at internal fluid pressure of 0.3 or 0.6
      MPa in terms of axial and rotational flexibilities of the L4-L5 motion segment.
      Axial flexibility was quantified by the axial displacement resulting from an
      axial compressive force of 400 N while the rotational flexibility by the range of
      motions determined as the rotational angles in response to a pure moment of 6.0
      Nm in flexion, extension, and right- and left-lateral bending directions. These
      tests were performed successively on the motion segment in the following
      conditions: intact, post nucleotomy, implanting BN with 0.3 MPa, and BN with 0.6
      MPa. The nucleotomy was found to significantly increase both the axial and
      rotational flexibilities while the implantation of the BN reduced the axial and
      rotational flexibilities to those of the intact segment. The axial and rotational
      flexibilities of the segment with the BN with 0.3 MPa were greater than those of
      the segment with the BN with 0.6 MPa. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:167-173, 2018.

PMID- 28513884
TI  - Oxidized Quasi-Carbon Nitride Quantum Dots Inhibit Ice Growth.
AB  - Antifreeze proteins (AFPs), a type of high-efficiency but expensive and often
      unstable biological antifreeze, have stimulated substantial interest in the
      search for synthetic mimics. However, only a few reported AFP mimics display
      thermal hysteresis, and general criteria for the design of AFP mimics remain
      unknown. Herein, oxidized quasi-carbon nitride quantum dots (OQCNs) are
      synthesized through an up-scalable bottom-up approach. They exhibit thermal
      hysteresis activity, an ice-crystal shaping effect, and activity on ice
      recrystallization inhibition. In the cryopreservation of sheep red blood cells,
      OQCNs improve cell recovery to more than twice that obtained by using a
      commercial cryoprotectant (hydroxyethyl starch) without the addition of any
      organic solvents. It is shown experimentally that OQCNs preferably bind onto the
      ice-crystal surface, which leads to the inhibition of ice-crystal growth due to
      the Kelvin effect. Further analysis reveals that the match of the distance
      between two neighboring tertiary N atoms on OQCNs with the repeated spacing of O
      atoms along the c-axis on the primary prism plane of ice lattice is critical for
      OQCNs to bind preferentially on ice crystals. Here, the application of graphitic
      carbon nitride derivatives for cryopreservation is reported for the first time.

PMID- 28513886
TI  - Regulating Water-Reduction Kinetics in Cobalt Phosphide for Enhancing HER
      Catalytic Activity in Alkaline Solution.
AB  - Electrochemical water splitting to produce hydrogen renders a promising pathway
      for renewable energy storage. Considering limited electrocatalysts have good
      oxygen-evolution reaction (OER) catalytic activity in acid solution while
      numerous economical materials show excellent OER catalytic performance in
      alkaline solution, developing new strategies that enhance the alkaline hydrogen
      evolution reaction (HER) catalytic activity of cost-effective catalysts is highly
      desirable for achieving highly efficient overall water splitting. Herein, it is
      demonstrated that synergistic regulation of water dissociation and optimization
      of hydrogen adsorption free energy on electrocatalysts can significantly promote
      alkaline HER catalysis. Using oxygen-incorporated Co2 P as an example, the
      synergistic effect brings about 15-fold enhancement of alkaline HER activity.
      Theory calculations confirm that the water dissociation free energy of Co2 P
      decreases significantly after oxygen incorporation, and the hydrogen adsorption
      free energy can also be optimized simultaneously. The finding suggests the
      powerful effectiveness of synergetic regulation of water dissociation and
      optimization of hydrogen adsorption free energy on electrocatalysts for alkaline
      HER catalysis.

PMID- 28513887
TI  - Geriatrics-for-Specialists Initiative: An Eleven-Specialty Collaboration to
      Improve Care of Older Adults.
AB  - In the early 1990s, visionary leaders at the American Geriatrics Society and The
      John A. Hartford Foundation recognized that the marked and growing shortage of
      geriatrics healthcare professionals would lead to a U.S. healthcare system ill
      prepared to provide optimal care for the ever-increasing number of older
      Americans. Led by the late Dennis W. Jahnigen, MD, they set forth a plan to
      address this shortage by collaborating with surgical and related medical
      specialists to create a series of programs to foster the highest quality care of
      older adults. Their unique programmatic vision was that every physician, not just
      geriatricians, would have basic knowledge and skills in geriatric care, because
      geriatricians cannot and should not meet the need alone.

PMID- 28513889
TI  - Mechanically induced bone formation is not sensitive to local osteocyte density
      in rat vertebral cancellous bone.
AB  - Osteocytes play an integral role in bone by sensing mechanical stimuli and
      releasing signaling factors that direct bone formation. The importance of
      osteocytes in mechanotransduction suggests that regions of bone tissue with
      greater osteocyte populations are more responsive to mechanical stimuli. To
      determine the effects of osteocyte population on bone functional adaptation we
      applied mechanical loads to the 8th caudal vertebra of skeletally mature female
      Sprague Dawley rats (6 months of age, n = 8 loaded, n = 8 sham controls). The
      distribution of tissue stress/strain within cancellous bone was determined using
      high-resolution finite element models, osteocyte distribution was determined
      using nano-computed tomography, and locations of bone formation were determined
      using three-dimensional images of fluorescent bone formation markers. Loading
      increased bone formation (3D MS/BS 10.82 +/- 2.09% in loaded v. 3.17 +/- 2.05% in
      sham control, mean +/- SD). Bone formation occurred at regions of cancellous bone
      experiencing greater tissue stress/strain, however stress/strain was only a
      modest predictor of bone formation; even at locations of greatest stress/strain
      the probability of observing bone formation did not exceed 41%. The local
      osteocyte population was not correlated with locations of new bone formation. The
      findings support the idea that local tissue stress/strain influence the locations
      of bone formation in cancellous bone, but suggest that the size of the osteocyte
      population itself is not influential. We conclude that other aspects of
      osteocytes such as osteocyte connectivity, lacunocanilicular nano-geometry,
      and/or fluid pressure/shear distributions within the marrow space may be more
      influential in regulating bone mechanotransduction than the number of osteocytes.
      (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
      Orthop Res 36:672-681, 2018.

PMID- 28513888
TI  - Pain, Quality of Life, and Safety Outcomes of Kyphoplasty for Vertebral
      Compression Fractures: Report of a Task Force of the American Society for Bone
      and Mineral Research.
AB  - The relative efficacy and harms of balloon kyphoplasty (BK) for treating
      vertebral compression fractures (VCF) are uncertain. We searched multiple
      electronic databases to March 2016 for randomized and quasi-randomized controlled
      trials comparing BK with control treatment (nonsurgical management [NSM],
      percutaneous vertebroplasty [PV], KIVA VCF treatment system [Benvenue Medical,
      Inc., Santa Clara, CA, USA], vertebral body stenting, or other) in adults with
      VCF. Outcomes included back pain, back disability, quality of life, new VCF, and
      adverse events (AEs). One reviewer extracted data, a second checked accuracy, and
      two rated risk of bias (ROB). Mean differences and 95% confidence intervals (CIs)
      were calculated using inverse-variance models. Risk ratios of new VCF and AE were
      calculated using Mantel-Haenszel models. Ten unique trials enrolled 1837
      participants (age range, 61 to 76 years; 74% female), all rated as having high or
      uncertain ROB. Versus NSM, BK was associated with greater reductions in pain,
      back-related disability, and better quality of life (k = 1 trial) that appeared
      to lessen over time, but were less than minimally clinically important
      differences. Risk of new VCF at 3 and 12 months was not significantly different
      (k = 2 trials). Risk of any AE was increased at 1 month (RR = 1.73; 95% CI, 1.36
      to 2.21). There were no significant differences between BK and PV in back pain,
      back disability, quality of life, risk of new VCF, or any AE (k = 1 to 3 trials).
      Limitations included lack of a BK versus sham comparison, availability of only
      one RCT of BK versus NSM, and lack of study blinding. Individuals with painful
      VCF experienced symptomatic improvement compared with baseline with all
      interventions. The clinical importance of the greater improvements with BK versus
      NSM is unclear, may be due to placebo effect, and may not counterbalance short
      term AE risks. Outcomes appeared similar between BK and other surgical
      interventions. Well-conducted randomized trials comparing BK with sham would help
      resolve remaining uncertainty about the relative benefits and harms of BK. (c)
      2017 American Society for Bone and Mineral Research.

PMID- 28513890
TI  - Risk of hospitalisation after early-revisit in the emergency department.
AB  - AIM: Early-revisits are frequent in the paediatric emergency department (ED)
      setting, but few data are available about early-revisited patients. The aim of
      this study was to investigate the hospitalisation rate of a population of early
      revisited patients and to detect if an early-revisited patient was at risk of a
      more severe disease. METHODS: Between June 2014 and January 2015, we conducted a
      retrospective cohort study, considering all patients presented to the ED of a
      tertiary level children's hospital in Italy. We selected all patients who were
      revisited within 72 h from the initial visit (study cohort), while all other
      patients accessed in the same period were considered the control cohort. The two
      cohorts were compared for age, gender, triage category, hospitalisation rate,
      diagnosis at admission and hospital length of stay. RESULTS: In the study period,
      we reviewed 10 750 visits, of which 430 (4%) were unplanned revisits for the same
      chief complaint within 72 h from the initial visit. Hospitalisation rate of early
      revisited patients was significantly higher compared to control patients (8.4 vs.
      2.9%). Hospitalisation rate increases in parallel with the number of revisits,
      but in many cases, it was not directly related to a worst triage category,
      neither to a longer hospital length of stay. CONCLUSION: Early revisited patients
      in the ED had a significantly higher risk of hospitalisation, but this risk was
      only partially related to their clinical conditions.

PMID- 28513891
TI  - Haematopoietic stem cell transplantation for severe combined immunodeficiency:
      Long-term health outcomes and patient perspectives.
AB  - AIM: To examine the long-term follow-up and health outcomes of patients who have
      undergone haematopoietic stem cell transplant (HSCT) for severe combined
      immunodeficiency (SCID). METHODS: Through a structured questionnaire, we examined
      follow-up arrangements and long-term health outcomes in 22 children who have had
      a successful HSCT for SCID during the period of 1984-2012 at the Sydney
      Children's Hospital, Sydney, Australia. RESULTS: Most children considered
      themselves healthy and 'cured' from SCID. Whilst many children enjoy relatively
      good bio-social health outcomes, specific negative health outcomes and
      absenteeism from school were perceived negatively. Two-thirds of children see
      their general practitioner or specialist regularly; however, there did not appear
      to be consistency with the nature of this follow-up. CONCLUSION: The findings
      from our study highlight the complex bio-psychosocial health needs of post-HSCT
      SCID children and encourage SCID centres to consider a multidisciplinary approach
      to their follow-up. Further studies into the determinants of patients'
      perceptions of their health are needed.

PMID- 28513892
TI  - Assessment of nonarteritic anterior ischemic optic neuropathy with intravoxel
      incoherent motion diffusion-weighted imaging using readout-segmented echo-planar
      imaging, parallel imaging, and 2D navigator-based reacquisition.
AB  - PURPOSE: To determine the feasibility of intravoxel incoherent motion (IVIM) for
      characterizing perfusion properties and its potential diagnostic utility for
      nonarteritic anterior ischemic optic neuropathy (NAION). IVIM diffusion-weighted
      imaging is a promising technique that can measure perfusion and diffusion
      characteristics simultaneously in a noninvasive manner. MATERIALS AND METHODS:
      Orbital IVIM in a 3.0T scanner was performed on 33 patients with NAION and 15
      controls using readout-segmented echo-planar imaging, parallel imaging, and 2D
      navigator-based reacquisition (RESOLVE-IVIM). Both visual field (VF) and visual
      acuity (VA) examinations were performed in 19 of the patients. The vascular
      volume fraction (f), diffusion coefficient (D), and pseudodiffusion coefficient
      (D*) were calculated for quantitative analysis. Additionally, correlation
      analyses of IVIM parameters with visual function were also performed. RESULTS:
      Affected optic nerves showed significantly lower f values than both unaffected
      contralateral nerves of the patients and nerves of the controls (P < 0.0001), and
      no significant difference for f was found between unaffected contralateral nerves
      and nerves of the controls (P = 0.1602). In addition, D and D* values showed no
      significant differences among the three groups (P = 0.0979, 0.0600, 0.6136 for D
      and 0.1779, 0.6253, 0.4743 for D*). Correlation analysis only demonstrated
      significant correlations between f values and the mean deviation of the visual
      field (r = 0.576, P = 0.0051). CONCLUSION: RESOLVE-IVIM measurement may reflect
      the perfusion abnormality and visual function impairment in NAION patients,
      demonstrating its potential application for the diagnosis and clinical evaluation
      of NAION. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson.
      Imaging 2017;46:1760-1766.

PMID- 28513894
TI  - The Dentoalveolar Prosthesis: A Novel Approach in the Reconstruction of Hard and
      Soft Tissue Deficiencies.
AB  - A clinical problem commonly encountered by the advanced restorative dentist is a
      requirement to replace missing teeth and the supporting alveolus in areas
      adjacent to healthy or manageable dentition. A potential solution could utilize a
      dentoalveolar prosthesis fabricated on two or more implants in the edentulous
      area. The implant substructure, or framework, may be cast, milled, or selectively
      laser melted from a variety of metals. A superstructure, or ceramic overlay
      incorporating a ceramic or composite resin gingival tissue component, is
      constructed to fit over the implant substructure and luted to the substructure
      with resin cement. This implant-supported fixed dental prosthesis identifies a
      solution for the replacement of both teeth and supporting alveolar bone. It
      restores comfort, function, and esthetics to the patient.

PMID- 28513893
TI  - Relationship between iodine levels and papillary thyroid carcinoma: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Iodine excess has been suggested as an exogenous risk factor of
      papillary thyroid cancer (PTC). We performed a systematic review and meta
      analysis to assess the relationship between iodine exposure measured in various
      forms and PTC prevalence. METHODS: We searched MEDLINE, Embase, and the Cochrane
      Library for case-control studies on iodine and PTC published up to December 2015.
      Exposure to iodine was compared between PTC and control groups. RESULTS: From the
      16 selected studies, the odds ratio (OR) for the overall effect size between high
      iodine exposure and PTC risk was 1.418 (95% confidence interval [CI] 1.054
      1.909). Based on 7 studies conducted in high iodinated regions, a positive
      association between iodine exposure and PTC was observed (OR 2.200; 95% CI 1.389
      3.483). CONCLUSION: This study demonstrated a higher exposure to iodine in
      patients with PTC compared with controls, especially for patients from high
      iodinated regions.

PMID- 28513895
TI  - One-year quality of life and functional outcomes of transoral robotic surgery for
      carcinoma of unknown primary.
AB  - BACKGROUND: The purpose of this study was to assess the quality of life (QOL)
      outcomes in patients who underwent transoral robotic surgery (TORS) for carcinoma
      of unknown primary (CUP). METHODS: Twenty-nine patients with CUP were
      administered the Head and Neck Cancer Inventory (HNCI) prospectively to evaluate
      QOL preoperatively and postoperatively. RESULTS: There was statistically and
      clinically significant deterioration in 2 of 4 domains (eating and social
      disruption) in the immediate aftermath of TORS. There was statistically and
      clinically meaningful deterioration in all 4 domains at 3 months relative to
      baseline, and there remained statistically and clinically meaningful
      deterioration in 2 of 4 domains at 6 months compared to baseline. These 2 domains
      remained statistically and clinically worse than baseline at 12 months. Speech
      and aesthetics domain scores were comparable at baseline and 12 months.
      CONCLUSION: Patients reported difficulties with eating and social disruption over
      the course of 1 year, but problems with speech and appearance abated.

PMID- 28513896
TI  - Management and outcomes of patients with recurrent neuroendocrine liver
      metastasis after curative surgery: An international multi-institutional analysis.
AB  - OBJECTIVE: We sought to characterize the treatment, as well as define the long
      term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM).
      METHODS: Between 1990 and 2014, 322 patients undergoing curative intent liver
      surgery for NELM were identified from a multi-institutional database. Recurrences
      were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic.
      RESULTS: Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and
      32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%)
      recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were
      alive without disease with a follow-up time >=3 years. The site of recurrence was
      intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra-
      and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence,
      extrahepatic only, and combined intra- and extra-hepatic recurrence were
      associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%,
      95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic,
      21.5%, 95%CI, 5.3-44.0) (P < 0.001). Most patients were treated with repeat
      surgery (n = 49, 36.6%), while 34 (23.5%) patients received a somatostatin
      analogue, 27 (18.6%) systemic cytotoxic chemotherapy, and 27 (21.4%) patients had
      intra-arterial therapy. Ten-year OS among patients who underwent repeat surgery
      or intra-arterial treatments was 60.3% (95%CI, 34.1-78.8) and 52.0% (95%CI, 30.6
      69.9), respectively. Patients who received somatostatin analogues (45.9% 95%CI,
      22.3-66.9) or systemic chemotherapy (0%) had a shorter long-term survival (P =
      0.001). CONCLUSION: Recurrence after surgery for NELM occurred among half of
      patients. Repeat liver resection for recurrence may offer a reasonable 5-year
      survival benefit.

PMID- 28513897
TI  - Quality and Survival of Direct Light-Activated Composite Resin Restorations in
      Posterior Teeth: A 5- to 20-Year Retrospective Longitudinal Study.
AB  - PURPOSE: To analyze the clinical success of direct light-activated composite
      resin restorations in posterior teeth. The quality of the margins and occlusal
      surfaces were evaluated, as well as their survival, according to their extensions
      and locations. The clinical performance of posterior composite resin restorations
      with different compositions were compared. All restorations were performed by the
      first author in his private practice, in a 5- to 20-year period. MATERIALS AND
      METHODS: Several types of composite resins, provided by different manufacturers,
      were placed in posterior teeth, after isolation with rubber dams. To be included
      in the study, the restorations had to have been in function for at least 5 years
      and had to have been placed between October 1993 and October 2008 by the first
      author. The established failure criteria were: tooth and/or restoration fracture,
      secondary caries, endodontic treatment, or tooth loss. Included patients must
      have been treated in the first author's office for at least 7 years and still in
      the practice through 2013; all patients had complete dental arches. Patients with
      removable dental prostheses or disabilities, who had moved, or who had died were
      excluded. Of 210 patients who fulfilled the inclusion criteria, 138 randomly
      selected subjects were clinically examined between November 2013 and April 2014.
      Of these 138 patients, 61 had received 105 direct-light-activated composite resin
      restorations in posterior teeth, which met the inclusion criteria. Twenty-nine
      patients (47.5%) underwent annual maintenance therapy. The patient-based data
      collected from clinical exams and personal records were recorded on a specially
      designed form. Age, gender, period of clinical attendance, tooth preparation,
      location, size, quality and longevity of the restorations, restorative materials,
      adhesive systems, parafunctional habits, secondary caries, and maintenance
      therapy were the variables evaluated. Authors were blinded to the clinical
      assessments. Cohen's Kappa coefficient of the quality analysis of the margins and
      occlusal surfaces of the restorations ranged from 0.78 to 1. Data processing was
      performed using Epidat software, v3.1, developed by the Conselleria de Sanidade
      de la Xunta de Galicia with the support of PAHO-WHO and SPSS software v13.0. If
      the number of complete values was too small, a Kaplan-Meier curve could not be
      used. Therefore the Fisher's exact test, Chi-square test, Kruskal-Wallis test,
      and Mann-Whitney non-parametric test were indicated to analyze significant
      differences. RESULTS: At the time of the examinations, 103 (98%) restorations
      were in function, and 98 (95.1%) were rated as clinically successful. Two
      restorations failed (2%). The observed mean survival time of restorations that
      remained functional was 11 years and 7 months. CONCLUSIONS: In the present
      report, direct light-activated composite resin restorations in posterior teeth
      showed a high clinical success rate and long-term mean survival time. These
      composite resins might be considered the material of choice to restore medium,
      extended, and in some clinical situations, large preparations in posterior teeth.

PMID- 28513898
TI  - Synthesis of BODIPY-Labeled Cholesterylated Glycopeptides by Tandem Click
      Chemistry for Glycocalyxification of Giant Unilamellar Vesicles (GUVs).
AB  - The glycocalyx cover membrane surfaces of all living cells. These complex
      architectures render their interaction mechanisms on the membrane surface
      difficult to study. Artificial cell-sized membranes with selected and defined
      glycosylation patterns may serve as a minimalistic approach to systematically
      study cell surface glycan interactions. The development of a facile general
      synthetic procedure for the synthesis of BODIPY-labeled cholesterylated
      glycopeptides, which can coat cell-size giant unilamellar vesicles (GUVs), is
      described. These peptide constructs were synthesized by: 1) solid-phase peptide
      synthesis (SPPS) using cholesterylated Fmoc-amino acids (Fmoc=9
      fluorenylmethoxycarbonyl) followed by tandem click reactions, 2) attachment of a
      BODIPY-bicyclononyne (BCN) (prepared by Mitsunobu chemistry via novel aryl BCN
      ethers) in the absence of a catalyst, and 3) glycosylation by means of copper(I)
      catalyzed click reaction of an azidoglycan. Seven different GUV-glycoforms were
      prepared and four of these were evaluated with their corresponding four specific
      anti-glycan binding lectins.

PMID- 28513900
TI  - Unraveling the Coulombic Forces in Electronically Decoupled Bichromophoric
      Systems during Two Successive Electron Transfers.
AB  - Coulombic forces are vital in modulating the electron transfer dynamics in both
      synthetic and biological polychromophoric assemblies, yet quantitative studies of
      the impact of such forces are rare, as it is difficult to disentangle
      electrostatic forces from simple electronic coupling. To address this problem,
      the impact of Coulombic interactions in the successive removal of two electrons
      from a model set of spirobifluorenes, where the interchromophoric electronic
      coupling is nonexistent, is quantitatively assessed. By systematically varying
      the separation of the bifluorene moieties using model compounds, ion pairing, and
      solvation, these interactions, with energies up to about 0.4 V, are absent at
      distances greater than about 9 A. These findings can be (quantitatively) applied
      for the design of polychromophoric assemblies, whereby the redox properties of
      donors and/or acceptors can be tuned by judicious positioning of the charged
      groups to control the electron-transfer dynamics.

PMID- 28513899
TI  - Surgical strategies and novel therapies for locally advanced pancreatic cancer.
AB  - Many patients with pancreatic cancer are not candidates for surgical resection
      due to involvement of critical mesenteric vascular structures. We compare and
      contrast the commonly used classification systems for borderline resectable and
      locally advanced pancreatic cancer. We describe the current strategies in
      managing venous and arterial involvement, as well as the role of neoadjuvant
      chemotherapy and chemoradiation, before explanding on a novel clinical trial in
      this patient population.

PMID- 28513901
TI  - Transcriptomic profiling reveals disordered regulation of surfactant homeostasis
      in neonatal cloned bovines with collapsed lungs and respiratory distress.
AB  - Respiratory distress is a major cause of mortality in cloned neonatal animals,
      but its pathogenesis remains poorly understood. Here, we used necropsy and
      histology procedures to evaluate the lungs of cloned neonatal bovines dying of
      respiratory distress, finding incomplete lung dilation, alveolar collapse, and
      thickened alveolar walls. Comparison of the transcriptomes between collapsed
      lungs of cloned bovines and their normal counterparts revealed 1373
      differentially expressed genes in collapsed lungs (p < 0.05, fold change >1.5 or
      <1.5-1 ), many of which were associated with surfactant biosynthesis, secretion,
      transport, recycling, and degradation. ERK/MAPK and Notch signaling pathways were
      among the canonical pathways relevant to surfactant homeostasis. Expression of
      the genes encoding Surfactant protein B (SPB) and Surfactant protein C (SPC)
      which control surfactant lipid packing, spreading, and stability-were
      significantly lower in collapsed lungs of cloned neonates at the transcript (p <
      0.01) and protein levels (p < 0.05) relative to that in normal lungs. Thus, our
      results provide an initial view into the changes in gene expression in cloned
      newborns with lung collapse and respiratory distress, and present a valuable
      resource for developing novel preventive or therapeutic strategies to reduce the
      mortality rate of cloned animals and to improve the efficiency of somatic cell
      nuclear transfer technology.

PMID- 28513902
TI  - Prospective analysis of radiation oncology image and plan-driven peer review for
      head and neck cancer.
AB  - BACKGROUND: Departmental "chart rounds" is an established form of review in
      radiation oncology, however, evidence is lacking that identifies links between
      features of a more subspecialized disease site-specific review and the likelihood
      and characteristics of recommendations made. We prospectively analyzed our head
      and neck group's review process to identify associations that could guide future
      practice. METHODS: Our group reviewed proposed management and treatment volumes
      for radiation simulated patients on a weekly basis, and we collected data
      encompassing recommendations made by individuals or group consensus. RESULTS:
      Changes in management, prescribed dose, radiation fractionation, clinical target
      volumes, or target contours were suggested in 85 of 182 cases. The most
      frequently recommended changes were adjustment of regions treated or target
      contours, and an inverse correlation was observed between the number of attending
      physicians present and specific changes suggested to the gross tumor volume
      (GTV). CONCLUSION: We find that site-specific head and neck peer review results
      in frequent recommendations largely independent of the type of case reviewed.

PMID- 28513911
TI  - Sperm capacitation pretreatment positively impacts bovine intracytoplasmic sperm
      injection.
AB  - The efficiency of intracytoplasmic sperm injection (ICSI) in bovines is low
      compared to other species due in part to inadequate egg activation and sperm
      nucleus decondensation after injection. We hypothesized that this low efficiency
      is due to the lack of complete sperm capacitation, so we evaluated the effects of
      isobutylmethylxanthine (IBMX) and methyl-beta-cyclodextrin (MbetaCD) on bovine
      sperm capacitation and on the preimplantation developmental potential of bovine
      embryos generated by ICSI. Treatment with IBMX and MbetaCD decreased sperm
      viability (between 13-30%); nevertheless, 0.4 mM IBMX and 1 mM MbetaCD increased
      (p < 0.05) capacitation metrics-that is, acrosome exocytosis, intracellular
      calcium level, plasma membrane fluidity, and tyrosine phosphorylation-compared to
      the control. After ICSI, embryos injected with IBMX- and MbetaCD-treated sperm
      showed similar cleavage to the untreated group (range 82-88%). Pronucleus
      formation rate was higher with MbetaCD-pretreatment (54%) compared to the control
      group (25%), and blastocyst rate was significantly improved with MbetaCD
      pretreatment (24%) compared to the IBMX (18%) and control (17%) groups.
      Importantly, embryo quality-as assessed by the total number of cells, cell
      allocation, and apoptotic cell index-was not affected by the sperm treatments. In
      conclusion, MbetaCD pretreatment of sperm improved the efficiency of blastocyst
      production in bovine ICSI.

PMID- 28513913
TI  - Determination of role of ceruloplasmin in oral potentially malignant disorders
      and oral malignancy-A cross-sectional study.
AB  - OBJECTIVES: In the process of carcinogenesis, lipid peroxidation and increased
      oxidative stress lead to changes in certain antioxidants. This study was aimed to
      assess and co-relate serum levels of ceruloplasmin in oral premalignancies and
      oral cancer so as to gauge its possible association with the process of
      carcinogenesis and to determine its role as tumor marker. MATERIAL AND METHODS:
      The study population comprised of 300 participants, equally divided into six
      study groups, that is, oral submucous fibrosis (OSMF), oral leukoplakia (OL),
      nicotina stomatitis (NS), oral malignancy (OM), controls (C), and healthy
      controls (HC); 5 ml of blood was collected from ante cubital vein from each
      participant. The serum was analyzed for ceruloplasmin levels using ERBA CHEM 5
      PLUS semiautomated chemistry analyzer and diagnostic kit by turbidimetric
      immunoassay. RESULTS: There were total 242 males and 58 females, who were between
      18 and 82 years of age, with a mean of 45.31 +/- 13.97 years. The serum
      ceruloplasmin levels were significantly increased in OM, OSMF, OL, and NS groups
      as compared to C and HC groups (p < .001). No statistically significant
      difference was found in intragroup analysis of the disease groups (p > .05).
      CONCLUSION: Serum ceruloplasmin can be used as diagnostic marker for oral
      premalignant and malignant lesions.

PMID- 28513914
TI  - Competition versus Cooperation in Catalytic Hydrogelators for anti-Selective
      Mannich Reaction.
AB  - Chemical systems find similarities in different sociological and biological
      processes, in which the entities compete or cooperate for a favorable outcome.
      The structural and functional adaptations leading to emergent properties,
      especially in catalysis, are based on factors such as abundance of substrates,
      stability of the transition state, and structural/functional attributes of
      catalysts. Proline and acid groups appended to catalytic fibers of two self
      sorting hydrogelators compete for the Mannich reaction between aniline,
      benzaldehyde, and cyclohexanone to give low overall selectivity (anti/syn 77:23).
      In a sol-gel system of the same molecules, on the other hand, the soluble acid
      appended molecules tend to cooperate with the fibers of proline-appended catalyst
      to give improved selectivity (anti/syn 95:5). The available options for the
      catalytic molecules are to carry out the reaction independently or in
      cooperation. However, these options are chosen based on the efficiency,
      selectivity, and mobility of catalysts as a result of their abilities to self
      assemble.

PMID- 28513912
TI  - Improving theranostics in pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is the fourth most deadly cancer in the United
      States, and is expected to be the second most deadly by 2030. The major
      difficulty in treating pancreatic cancer is the late onset of symptoms.
      Generally, patients show metastatic disease by the time of diagnosis, with a
      survival rate of 5% beyond 5 years. In patients without metastatic disease,
      surgical resection increases 5 year survival rate to 25%. The remaining 75%
      succumb to undetected metastases. Clearly, improvements to both detection,
      surgical intervention, and therapeutic strategies will be needed to improve
      patient outcome in pancreatic cancer. METHODS: Recent literature has been
      surveyed and atomic models of new therapeutic approaches were generated. RESULTS
      AND CONCLUSIONS: Here, we focus on the recent progress employing monoclonal
      antibodies (mAbs) to target pancreatic cancer associated markers, and more
      specifically on recent chemical and protein engineering efforts to improve the
      homogeneity, stability, and administration of mAbs to precisely deliver imaging
      agents and cytotoxins to sites of disease.

PMID- 28513915
TI  - Impact of "a" determinant mutations on detection of hepatitis B surface antigen
      (HBsAg) in HBV strains from Chinese patients with occult hepatitis B.
AB  - This study was designed to detect mutations that occur within the "a" determinant
      in the S gene of the hepatitis B virus (HBV) in patients with occult hepatitis B
      (OHB), and to analyze the influence of these mutations on expression and
      reactivity of the hepatitis B surface antigen (HBsAg). Twenty-three certified OHB
      samples were compared to 32 HBsAg positive samples from patients with chronic
      hepatitis B. The median HBV DNA levels in the OHB group were significantly lower
      than those in the control group (P < 0.0001). Mutations within the "a"
      determinant were analyzed by gene amplification and sequencing. This revealed
      mixed infections in which clones within a sample displayed either different
      mutations or mutations in association with clones that exhibited wild type amino
      acid patterns. Sequencing analysis also showed a significant difference between
      the proportions of amino acid mutations observed in the OHB and control groups.
      Seven recombinant S (rS) proteins with corresponding OHB mutations and three wild
      type alleles were expressed and purified in the Pichia pastoris expression system
      to preserve conformational attributes, and their reactivity analyzed using six
      commercial HBsAg assays. The OHB sera were HBsAg nonreactive while the rS
      proteins with corresponding OHB mutations were universally reactive. Thus, we
      postulate that the reduced binding affinity between mutated HBsAg and its
      antibody may not be as important in defining OHB as is the effect of specific
      mutations in the preS/S region of the genome that affect the synthesis and
      secretion of the S protein and/or the virion.

PMID- 28513917
TI  - Fragment Screening against the EthR-DNA Interaction by Native Mass Spectrometry.
AB  - Native nanoelectrospray ionization mass spectrometry is an underutilized
      technique for fragment screening. In this study, the first demonstration is
      provided of the use of native mass spectrometry for screening fragments against a
      protein-DNA interaction. EthR is a transcriptional repressor of EthA expression
      in Mycobacterium tuberculosis (Mtb) that reduces the efficacy of ethionamide, a
      second-line antitubercular drug used to combat multidrug-resistant Mtb strains. A
      small-scale fragment screening campaign was conducted against the EthR-DNA
      interaction using native mass spectrometry, and the results were compared with
      those from differential scanning fluorimetry, a commonly used primary screening
      technique. Hits were validated by surface plasmon resonance and X-ray
      crystallography. The screening campaign identified two new fragments that disrupt
      the EthR-DNA interaction in vitro (IC50 =460-610 MUm) and bind to the hydrophobic
      channel of the EthR dimer.

PMID- 28513916
TI  - Global forest carbon uptake due to nitrogen and phosphorus deposition from 1850
      to 2100.
AB  - Spatial patterns and temporal trends of nitrogen (N) and phosphorus (P)
      deposition are important for quantifying their impact on forest carbon (C)
      uptake. In a first step, we modeled historical and future change in the global
      distributions of the atmospheric deposition of N and P from the dry and wet
      deposition of aerosols and gases containing N and P. Future projections were
      compared between two scenarios with contrasting aerosol emissions. Modeled fields
      of N and P deposition and P concentration were evaluated using globally
      distributed in situ measurements. N deposition peaked around 1990 in European
      forests and around 2010 in East Asian forests, and both increased sevenfold
      relative to 1850. P deposition peaked around 2010 in South Asian forests and
      increased 3.5-fold relative to 1850. In a second step, we estimated the change in
      C storage in forests due to the fertilization by deposited N and P (?Cnu dep ),
      based on the retention of deposited nutrients, their allocation within plants,
      and C:N and C:P stoichiometry. ?Cnu dep for 1997-2013 was estimated to be 0.27 +/
      0.13 Pg C year-1 from N and 0.054 +/- 0.10 Pg C year-1 from P, contributing 9%
      and 2% of the terrestrial C sink, respectively. Sensitivity tests show that
      uncertainty of ?Cnu dep was larger from P than from N, mainly due to uncertainty
      in the fraction of deposited P that is fixed by soil. ?CPdep was exceeded by
      ?CNdep over 1960-2007 in a large area of East Asian and West European forests due
      to a faster growth in N deposition than P. Our results suggest a significant
      contribution of anthropogenic P deposition to C storage, and additional sources
      of N are needed to support C storage by P in some Asian tropical forests where
      the deposition rate increased even faster for P than for N.

PMID- 28513918
TI  - Cyclic Polysiloxanes with Linked Cyclotetrasiloxane Subunits.
AB  - Cyclic polymers are an important class of macromolecules, but the structural
      diversity of the backbone is limited. Herein we report the use of the Piers
      Rubinsztajn reaction for the one-step synthesis of cyclic polysiloxanes with
      novel structural features. Specifically, the B(C6 F5 )3 -catalyzed coupling of
      various organic tris(dimethylsiloxy)silane and trialkoxysilane compounds
      generated a series of cyclic polysiloxanes with cyclotetrasiloxane subunits. The
      thiolated cyclic polymers were also shown to be effective in directing the
      circular assembly gold nanoparticles. The presence of constrained rings in the
      backbone is unprecedented and may offer opportunities for novel applications of
      these cyclic polymers.

PMID- 28513919
TI  - Functional status and mortality prediction in community-acquired pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Poor functional status (FS) has been suggested as a
      poor prognostic factor in both pneumonia and severe pneumonia in elderly
      patients. However, it is still unclear whether FS is associated with outcomes and
      improves survival prediction in community-acquired pneumonia (CAP) in the general
      population. METHODS: Data on hospitalized patients with CAP and FS, assessed by
      the Eastern Cooperative Oncology Group (ECOG) scale were prospectively collected
      between January 2008 and December 2012. The independent association of FS with 30
      day mortality in CAP patients was evaluated using multivariable logistic
      regression. Improvement in mortality prediction when FS was added to the CRB-65
      (confusion, respiratory rate, blood pressure and age 65) score was evaluated for
      discrimination, reclassification and calibration. RESULTS: The 30-day mortality
      of study participants (n = 1526) was 10%. Mortality significantly increased with
      higher ECOG score (P for trend <0.001). In multivariable analysis, ECOG >=3 was
      strongly associated with 30-day mortality (adjusted OR: 5.70; 95% CI: 3.82-8.50).
      Adding ECOG >=3 significantly improved the discriminatory power of CRB-65.
      Reclassification indices also confirmed the improvement in discrimination ability
      when FS was combined with the CRB-65, with a categorized net reclassification
      index (NRI) of 0.561 (0.437-0.686), a continuous NRI of 0.858 (0.696-1.019) and a
      relative integrated discrimination improvement in the discrimination slope of
      139.8 % (110.8-154.6). CONCLUSION: FS predicted 30-day mortality and improved
      discrimination and reclassification in consecutive CAP patients. Assessment of
      premorbid FS should be considered in mortality prediction in patients with CAP.

PMID- 28513920
TI  - Moisture-induced greening of the South Asia over the past three decades.
AB  - South Asia experienced a weakening of summer monsoon circulation in the past
      several decades, resulting in rainfall decline in wet regions. In comparison with
      other tropical ecosystems, quantitative assessments of the extent and triggers of
      vegetation change are lacking in assessing climate-change impacts over South Asia
      dominated by crops. Here, we use satellite-based Normalized Difference Vegetation
      Index (NDVI) to quantify spatial-temporal changes in vegetation greenness, and
      find a widespread annual greening trend that stands in contrast to the weakening
      of summer monsoon circulation particularly over the last decade. We further show
      that moisture supply is the primary factor limiting vegetation activity during
      dry season or in dry region, and cloud cover or temperature would become
      increasingly important in wet region. Enhanced moisture conditions over dry
      region, coinciding with the decline in monsoon, are mainly responsible for the
      widespread greening trend. This result thereby cautions the use of a unified
      monsoon index to predict South Asia's vegetation dynamics. Current climate-carbon
      models in general correctly reproduce the dominant control of moisture in the
      temporal characteristics of vegetation productivity. But the model ensemble
      cannot exactly reproduce the spatial pattern of satellite-based vegetation change
      mainly because of biases in climate simulations. The moisture-induced greening
      over South Asia, which is likely to persist into the wetter future, has
      significant implications for regional carbon cycling and maintaining food
      security.

PMID- 28513921
TI  - Chitin-induced and CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) phosphorylation
      dependent endocytosis of Arabidopsis thaliana LYSIN MOTIF-CONTAINING RECEPTOR
      LIKE KINASE5 (LYK5).
AB  - To detect potential pathogens, plants perceive the fungal polysaccharide chitin
      through receptor complexes containing lysin motif receptor-like kinases (LysM
      RLKs). To investigate the ligand-induced spatial dynamics of chitin receptor
      components, we studied the subcellular behaviour of two Arabidopsis thaliana LysM
      RLKs involved in chitin signalling, CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) and
      LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE5. We performed standard and
      quantitative confocal laser scanning microscopy on stably transformed A. thaliana
      plants expressing fluorescently tagged CERK1 and LYK5 from their native
      promoters. Microscopy approaches were complemented by biochemical analyses in
      plants and in vitro. Both CERK1 and LYK5 localized to the plasma membrane and
      showed constitutive endomembrane trafficking. After chitin treatment, however,
      CERK1 remained at the plasma membrane while LYK5 relocalized into mobile
      intracellular vesicles. Detailed analyses revealed that chitin perception
      transiently induced the internalization of LYK5 into late endocytic compartments.
      Plants that lacked CERK1 or expressed an enzymatically inactive CERK1 variant did
      not exhibit chitin-induced endocytosis of LYK5. CERK1 could phosphorylate LYK5 in
      vitro and chitin treatment induced CERK1-dependent phosphorylation of LYK5 in
      planta. Our results suggest that chitin-induced phosphorylation by CERK1 triggers
      LYK5 internalization. Thus, our work identifies phosphorylation as a key
      regulatory step in endocytosis of plant RLKs and also provides evidence for
      receptor complex dissociation after ligand perception.

PMID- 28513922
TI  - Impact of sampling interval in training data acquisition on intrafractional
      predictive accuracy of indirect dynamic tumor-tracking radiotherapy.
AB  - PURPOSE: To explore the effect of sampling interval of training data acquisition
      on the intrafractional prediction error of surrogate signal-based dynamic tumor
      tracking using a gimbal-mounted linac. MATERIALS AND METHODS: Twenty pairs of
      respiratory motions were acquired from 20 patients (ten lung, five liver, and
      five pancreatic cancer patients) who underwent dynamic tumor-tracking with the
      Vero4DRT. First, respiratory motions were acquired as training data for an
      initial construction of the prediction model before the irradiation. Next,
      additional respiratory motions were acquired for an update of the prediction
      model due to the change of the respiratory pattern during the irradiation. The
      time elapsed prior to the second acquisition of the respiratory motion was 12.6
      +/- 3.1 min. A four-axis moving phantom reproduced patients' three dimensional
      (3D) target motions and one dimensional surrogate motions. To predict the future
      internal target motion from the external surrogate motion, prediction models were
      constructed by minimizing residual prediction errors for training data acquired
      at 80 and 320 ms sampling intervals for 20 s, and at 500, 1,000, and 2,000 ms
      sampling intervals for 60 s using orthogonal kV x-ray imaging systems. The
      accuracies of prediction models trained with various sampling intervals were
      estimated based on training data with each sampling interval during the training
      process. The intrafractional prediction errors for various prediction models were
      then calculated on intrafractional monitoring images taken for 30 s at the
      constant sampling interval of a 500 ms fairly to evaluate the prediction accuracy
      for the same motion pattern. In addition, the first respiratory motion was used
      for the training and the second respiratory motion was used for the evaluation of
      the intrafractional prediction errors for the changed respiratory motion to
      evaluate the robustness of the prediction models. RESULTS: The training error of
      the prediction model was 1.7 +/- 0.7 mm in 3D for all sampling intervals. The
      intrafractional prediction error for the same motion pattern was 1.9 +/- 0.7 mm
      in 3D for an 80 ms sampling interval, which increased larger than 1 mm in 10.0%
      of prediction models trained at a 2,000 ms sampling interval with a significant
      difference (P < 0.01) and up to 2.5% for the other sampling intervals without a
      significant difference (P > 0.05). The intrafractional prediction error for the
      changed respiratory motion pattern increased to 5.1 +/- 2.4 mm in 3D for an 80 ms
      sampling interval; however, there was not a significant difference in the
      robustness of the prediction model between the 80 ms sampling interval and other
      sampling intervals (P > 0.05). CONCLUSIONS: Although the training error of the
      prediction model was consistent for the all sampling intervals, the prediction
      model using the larger sampling interval of the 2,000 ms increased the
      intrafractional prediction error for the same motion pattern. The realistic
      accuracy of the prediction model was difficult to estimate using the larger
      sampling interval during the training process. It is recommended to construct the
      prediction model at sampling interval <= 1,000 ms and to reconstruct the model
      during treatment.

PMID- 28513923
TI  - Histological variability and consequences in chronic bird-related
      hypersensitivity pneumonitis.
AB  - BACKGROUND AND OBJECTIVE: Lobar and temporal histological variability in chronic
      bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated.
      This study was designed to evaluate the spatio-temporal histopathological
      variability in chronic BRHP. METHODS: Fifty-two patients with chronic BRHP who
      underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The
      histopathological characteristics of the lung biopsy specimens were classified by
      the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS)
      consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy
      specimens from seven patients were also evaluated to examine the serial changes
      from SLB to autopsy. RESULTS: In a study of lobar histological variability based
      on the findings of SLB, 7 patients were diagnosed with cellular nonspecific
      interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with
      fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP)
      pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential
      changes, specimens of SLBs with fibrotic NSIP pattern changed to a
      bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern.
      CONCLUSION: Interlobar and intralobar histological variability is present in
      chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may
      be an early lesion that progresses to a UIP pattern.

PMID- 28513924
TI  - Glycan Fingerprinting via Cold-Ion Infrared Spectroscopy.
AB  - The diversity of stereochemical isomers present in glycans and glycoconjugates
      poses a formidable challenge for comprehensive structural analysis. Typically,
      sophisticated mass spectrometry (MS)-based techniques are used in combination
      with chromatography or ion-mobility separation. However, coexisting structurally
      similar isomers often render an unambiguous identification impossible. Other
      powerful techniques such as gas-phase infrared (IR) spectroscopy have been
      limited to smaller glycans, since conformational flexibility and thermal
      activation during the measurement result in poor spectral resolution. This
      limitation can be overcome by using cold-ion spectroscopy. The vibrational
      fingerprints of cold oligosaccharide ions exhibit a wealth of well-resolved
      absorption features that are diagnostic for minute structural variations. The
      unprecedented resolution of cold-ion spectroscopy coupled with tandem MS may
      render this the key technology to unravel complex glycomes.

PMID- 28513937
TI  - John R. Cameron.

PMID- 28513947
TI  - Response to "Comment on 'Update of AAPM Task Group No. 43 Report: A revised AAPM
      protocol for brachytherapy dose calculations' " [Med. Phys. 31, 633-674 (2004)].

PMID- 28513968
TI  - The views of ethics committee members and medical researchers on the return of
      individual research results and incidental findings, ownership issues and benefit
      sharing in biobanking research in a South Indian city.
AB  - The return of individual research results and incidental findings from biobanking
      research is a much debated ethical issue globally but has extensive relevance in
      India where the burden of out of pocket health care expenses is high for the
      majority. The views of 21 ethics committee (EC) members and 22 researchers from
      Bengaluru, India, concerning the ethics of biobanking research were sought
      through in-depth interviews using an unfolding case vignette with probes. A
      shared view among most was that individual research results which are
      'actionable' or have 'clinical significance' should be returned to the sample
      contributors through their treating physicians. This was seen as an ethical
      obligation and a moral duty on the side of the researcher to "give back" to the
      person who contributed to the research. The challenges foreseen were that of
      resources, both financial and personnel, for the time and counseling needed to
      accompany the disclosure of results. Perceptions of 'ownership' appear to
      influence the concept of benefit sharing. While benefit sharing in financial
      terms was considered ethically challenging, certain researchers and ethics
      committee members made a case for "two way altruism" where the researcher in
      return for the altruistic 'valuable contribution', shares with the contributor/
      community, benefits of the research which could include research findings,
      improved patient care, and more affordable access to the new diagnostic tests or
      products arising from the research. This defines the emerging ethic of "giving
      back" which goes beyond individual rights and ensures reciprocity and
      distributive justice.

PMID- 28513969
TI  - Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or
      Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence
      Crossover Study.
AB  - Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus
      protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane
      transporters. The objective of this study was to evaluate the effect of steady
      state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin
      or rosuvastatin. In this single-center, open-label, fixed-sequence crossover
      study, 33 healthy adult male and female volunteers were given either atorvastatin
      10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently
      received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by
      240 mg faldaprevir once daily from day 6 to day 10, with an additional single
      dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples
      for the statins were collected on days 1-3 and days 10-12. Concomitant
      administration with faldaprevir led to approximately 9-fold and 34-fold increases
      in AUC0-infinity and Cmax , respectively, of atorvastatin and approximately 15
      fold and 33-fold increases in AUC0-infinity and Cmax , respectively, of
      rosuvastatin, compared with the statins given alone. Exposure to the major
      metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased
      to a similar magnitude as that of the parent compounds. The marked drug-drug
      interaction observed is most likely related to the inhibitory effects of
      faldaprevir on transporters, particularly hepatic uptake transporters such as
      OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in
      healthy volunteers, coadministration of faldaprevir with statins should be
      avoided.

PMID- 28513970
TI  - Cytomegalovirus infection and atherosclerosis risk: A meta-analysis.
AB  - Human cytomegalovirus (HCMV) infection is an important risk factor for
      atherosclerosis (AS). Numerous studies have been conducted to analyze the
      association between HCMV infection and risk of AS, but no clear consensus has
      been reached. So the objective of this paper was aimed to demonstrate the
      relationship between HCMV and AS by doing a meta-analysis. Relative literature
      was searched through the electronic databases PubMed, Embase, and CNKI. Data were
      accurately assessed and analyzed independently by two investigators. Ultimately,
      the 30 studies, involving 3328 cases and 2090 controls were included in our meta
      analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively,
      63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in
      case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were,
      respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26%
      (28/229) in control subjects. The positive ratio of HCMV infection was higher in
      atherosclerosis group than that in non-atherosclerosis group. Especially in Asian
      group, calculated odds ratios for the presence of HCMV infection in IgG-based
      HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as
      OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17
      25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The
      meta-analysis results showed that HCMV infection is significant connected with an
      increased risk for AS.

PMID- 28513971
TI  - Predictors and the distal outcome of general Internet use: The identification of
      children's developmental trajectories.
AB  - This study examined the predictors and distal outcome in relation to the
      frequency of online activities and investigated the presence of prototypical
      trajectories following different patterns of general Internet use over 5 years.
      The data set consisted of a nationally representative sample of 2,840 fourth
      graders (Mage  = 9.86 years) in South Korea at baseline. Analyses revealed rank
      order stability in general Internet use with four latent classes: high stable
      (5.8%), high quadratic (20.3%), moderate stable (32.7%), and low stable (41.2%).
      Youth with higher levels of perceived parental monitoring knowledge, friendship
      closeness, and depressed mood at baseline were more likely to belong to the high
      stable class, while girls were more likely to be in the high quadratic or
      moderate stable classes relative to the low stable class. The high stable class
      had the greatest odds of reporting alcohol use at grade eight, whereas the low
      stable class had the lowest odds. Statement of contribution What is already known
      on this subject? Internet usage increases as children progress through to early
      adolescence and then levels off Longitudinal data have shown that adolescents'
      greater Internet use is predictive of their higher levels of drinking What does
      this study add? To explore different developmental pathways of Internet use in
      relation to its antecedents and distal outcome Early adolescents who spend more
      time on the Internet have a greater chance of starting to drink The
      interindividual rank-order stability of general Internet usage exists at least
      before late childhood.

PMID- 28513972
TI  - Stigma in science: the case of earthquake prediction.
AB  - This paper explores how earthquake scientists conceptualise earthquake
      prediction, particularly given the conviction of six earthquake scientists for
      manslaughter (subsequently overturned) on 22 October 2012 for having given
      inappropriate advice to the public prior to the L'Aquila earthquake of 6 April
      2009. In the first study of its kind, semi-structured interviews were conducted
      with 17 earthquake scientists and the transcribed interviews were analysed
      thematically. The scientists primarily denigrated earthquake prediction, showing
      strong emotive responses and distancing themselves from earthquake 'prediction'
      in favour of 'forecasting'. Earthquake prediction was regarded as impossible and
      harmful. The stigmatisation of the subject is discussed in the light of research
      on boundary work and stigma in science. The evaluation reveals how mitigation
      becomes the more favoured endeavour, creating a normative environment that
      disadvantages those who continue to pursue earthquake prediction research.
      Recommendations are made for communication with the public on earthquake risk,
      with a focus on how scientists portray uncertainty.

PMID- 28513973
TI  - Width/Length Ratio in Maxillary Anterior Teeth. Comparative Study of Esthetic
      Preferences among Professionals and Laypersons.
AB  - PURPOSE: Many studies have examined the esthetic preferences of professionals in
      the maxillary anterior region; however, only a few have taken into account the
      ratios that are more frequent within the population or other ratios suggested in
      the literature as ideal. Previous studies also failed to compare them with the
      esthetic preferences of the lay population with regards to the smile. The purpose
      of this study is to highlight the differences when perceiving the esthetics of
      smiles between general dentists and laypersons, and linking them with the
      width/length of the maxillary anterior teeth. MATERIALS AND METHODS: Photographs
      of the full face of a female subject were modified with Photoshop CS regarding
      the length/width relationships of the 6 maxillary anterior teeth. The three
      modifications made were: (a) 80% length/width, (b) 85%, length/width, and (c) 85%
      length/width in central incisors, 80% length/width in lateral incisors and
      canines. Three sequences of photograph pairs were created with different ratios
      and presented in PowerPoint to a sample of 100 general dentists and 100
      laypersons. RESULTS: The ratio considered as the most esthetic by the majority of
      the judges was 85% for central incisors and 80% for lateral incisors and canines,
      with a statistically significant difference (p < 0.01). There was no
      statistically significant difference in the esthetic preferences of the studied
      populations either due to gender or professional experience of the dentists (p >
      0.01). CONCLUSIONS: According to the results obtained in this study,
      professionals and laypersons considered a width/length ratio of 85% for maxillary
      central incisors and 80% for lateral incisors and canines as the most esthetic
      for maxillary anterior teeth. These results do not support findings from other
      studies previously published with similar ratios in central incisors, lateral
      incisors, and canines. CLINICAL IMPLICATION: Today clinicians practice in a
      treatment environment where not only function and utility but also esthetics is
      demanded in almost every procedure. Restoring/maintaining function is considered
      essential in any restorative dentistry treatment, but the esthetic aspects of any
      treatment should never be forgotten. This study was motivated by the increasing
      importance of obtaining a better appreciation of the perception of smile beauty,
      and of the role of maxillary teeth width/length ratio on the perception of dental
      esthetics.

PMID- 28513974
TI  - Fecal microbiota transplantation outcomes in immunocompetent and
      immunocompromised patients: A single-center experience.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a major infectious disease
      focus for which fecal microbiota transplantation (FMT) has been used with success
      in various patient populations. METHODS: We conducted a retrospective study of
      FMT in immunocompetent and immunocompromised patients to review outcomes at our
      center, with a focus on identifying risk factors for FMT failure in solid organ
      transplant (SOT) patients. FMT was conducted using universal banked frozen stool
      via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per
      our institutional protocol. RESULTS: Thirteen patients were included in the
      analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these,
      6 patients had a history of SOT and were primarily abdominal organ recipients.
      All immunocompetent patients experienced success with FMT, while 3
      immunocompromised SOT patients experienced failure. Two patients who failed FMT
      had a second FMT, which was successful in one patient and failed in the second
      patient. No adverse events were noted with FMT administration. A predictor of FMT
      failure was antimicrobial exposure pre-FMT. CONCLUSIONS: This study highlights
      the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised
      patients. Antimicrobial exposure prior to FMT was an identified risk factor for
      FMT failure. The use of sequential FMT in SOT patients may be considered but
      ultimately requires further investigation.

PMID- 28513975
TI  - Opioids for the Treatment of Pain: The Risk of Treating a Multivariate Symptom.

PMID- 28513977
TI  - Use of High Performance Polymers as Dental Implant Abutments and Frameworks: A
      Case Series Report.
AB  - Dental implant abutments can be made of different materials including titanium,
      gold, zirconia, alumina, and polymeric materials. Polyetheretherketone (PEEK) is
      a high performance thermoplastic polymer that can be used as a dental implant
      abutment material. It has an elastic modulus comparable to bone and can reduce
      stress shielding. PEEK is a radiolucent material that can allow better
      radiographic imaging of peri-implant tissues and can be veneered with composite
      materials or bonded to ceramics. PEEK is widely used in orthopedic and spinal
      surgeries, and it possesses mechanical and biological characteristics that
      encourage its use as dental implant abutments. This article will review the use
      of PEEK in dentistry and in particular as a dental implant abutment and over
      implant framework. Clinical reports will be presented to suggest some uses of
      PEEK materials in implant dentistry.

PMID- 28513978
TI  - Unilateral nevoid telangiectasia in two adolescents.

PMID- 28513976
TI  - Gingerenone A Attenuates Monocyte-Endothelial Adhesion via Suppression of I Kappa
      B Kinase Phosphorylation.
AB  - During the early stages of atherosclerosis, monocytes bind and migrate into the
      endothelial layer, promoting inflammation within the aorta. In order to prevent
      the development of atherosclerosis, it is critical to inhibit such inflammation.
      The therapeutic effects of ginger have been investigated in several models of
      cardiovascular disease. However, although a number of previous studies have
      focused on specific compounds, the mechanisms of action responsible remain
      unclear. Here, we investigated five major compounds present in ginger, and
      observed that gingerenone A exhibited the strongest inhibitory effects against
      tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS) induced monocyte
      endothelial adhesion. Furthermore, gingerenone A significantly suppressed the
      expression of TNF-alpha and LPS-induced vascular cell adhesion molecule-1 (VCAM
      1) and chemokine (C-C motif) ligand 2 (CCL2), key mediators of the interaction
      between monocytes, and endothelial cells. Transactivation of nuclear factor
      kappaB (NF-kappaB), which is a key transcription factor of VCAM-1 and CCL2, was
      induced by TNF-alpha and LPS, and inhibited by treatment of gingerenone A.
      Gingerenone A also inhibited the phosphorylation of NF-kappaB inhibitor (IkappaB)
      alpha and IkappaB Kinase. Taken together, these results demonstrate that
      gingerenone A attenuates TNF-alpha and LPS-induced monocyte adhesion and the
      expression of adhesion factors in endothelial cells via the suppression of NF
      kappaB signaling. J. Cell. Biochem. 119: 260-268, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28513979
TI  - Identification of a de novo variant in CHUK in a patient with an EEC/AEC syndrome
      like phenotype and hypogammaglobulinemia.
AB  - The cardinal features of Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate
      (EEC), and Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndromes
      are ectodermal dysplasia (ED), orofacial clefting, and limb anomalies. EEC and
      AEC are caused by heterozygous mutations in the transcription factor p63 encoded
      by TP63. Here, we report a patient with an EEC/AEC syndrome-like phenotype,
      including ankyloblepharon, ED, cleft palate, ectrodactyly, syndactyly, additional
      hypogammaglobulinemia, and growth delay. Neither pathogenic mutations in TP63 nor
      CNVs at the TP63 locus were identified. Exome sequencing revealed de novo
      heterozygous variants in CHUK (conserved helix-loop-helix ubiquitous kinase),
      PTGER4, and IFIT2. While the variant in PTGER4 might contribute to the
      immunodeficiency and growth delay, the variant in CHUK appeared to be most
      relevant for the EEC/AEC-like phenotype. CHUK is a direct target gene of p63 and
      encodes a component of the IKK complex that plays a key role in NF-kappaB pathway
      activation. The identified CHUK variant (g.101980394T>C; c.425A>G; p.His142Arg)
      is located in the kinase domain which is responsible for the phosphorylation
      activity of the protein. The variant may affect CHUK function and thus contribute
      to the disease phenotype in three ways: (1) the variant exhibits a dominant
      negative effect and results in an inactive IKK complex that affects the canonical
      NF-kappaB pathway; (2) it affects the feedback loop of the canonical and non
      canonical NF-kappaB pathways that are CHUK kinase activity-dependent; and (3) it
      disrupts NF-kappaB independent epidermal development that is often p63-dependent.
      Therefore, we propose that the heterozygous CHUK variant is highly likely to be
      causative to the EEC/AEC-like and additional hypogammaglobulinemia phenotypes in
      the patient presented here.

PMID- 28513980
TI  - Solid-State Carbon Dots with Red Fluorescence and Efficient Construction of Dual
      Fluorescence Morphologies.
AB  - Stable solid-state red fluorescence from organosilane-functionalized carbon dots
      (CDs) with sizes around 3 nm is reported for the first time. Meanwhile, a novel
      method is also first reported for the efficient construction of dual-fluorescence
      morphologies. The quantum yield of these solid-state CDs and their aqueous
      solution is 9.60 and 50.7%, respectively. The fluorescence lifetime is 4.82 ns
      for solid-state CDs, and 15.57 ns for their aqueous solution. These CDs are
      detailedly studied how they can exhibit obvious photoluminescence overcoming the
      self-quenching in solid state. Luminescent materials are constructed with dual
      fluorescence based on as-prepared single emissive CDs (red emission) and
      nonfluorescence media (starch, Al2 O3 , and RnOCH3 COONa), with the
      characteristic peaks located at nearly 440 and 600 nm. Tunable photoluminescence
      can be successfully achieved by tuning the mass ratio of CDs to solid matrix
      (such as starch). These constructed dual-fluorescence CDs/starch composites can
      also be applied in white light-emitting diodes with UV chips (395 nm), and oxygen
      sensing.

PMID- 28513981
TI  - Exposure to fermentation supernatant of Staphylococcus aureus accelerated
      dedifferentiation of chondrocytes and production of antimicrobial peptides.
AB  - Staphylococcus aureus (S. aureus) is the most popular pathogen found in septic
      arthritis. Despite bacteria was eradicated from joint cavity during acute
      infection, destruction of articular cartilage often continues for years, leading
      to permanent joint damage. The mechanism responsible for this consistent
      catabolic reaction in septic arthritis remains unclear. Here, we found that
      fermentation supernatant (FS) of S. aureus accelerated dedifferentiation of
      chondrocytes and induced expression of catabolic factors including A Disintegrin
      like and Metalloproteinase with Thrombospondin-1 motifs 5, NO synthase 2, matrix
      metalloproteinase-3, -13. In response to FS of S. aureus stimulation, expression
      of antimicrobial peptides (AMPs) including beta-defensin-1, -2, -3, -4,
      cathelicidin antimicrobial peptide (CAMP) in dedifferentiated chondrocytes was
      significantly higher than that in chondrocytes which maintained their
      differentiated phenotype. Among AMPs detected, expression of CAMP in
      dedifferentiated chondrocytes was observed to increase 170 times higher than that
      in differentiated ones. When exposed to FS of S. aureus, expression of
      interleukin (IL)-1beta, IL-17F, and IL-22 were remarkably increased in
      dedifferentiated chondrocytes. These results indicated that dedifferentiation of
      chondrocytes caused by exposure to S. aureus might be responsible for secondary
      osteoarthritis (OA) after acute S. aureus infection in joint. While, one
      potential benefit of dedifferentiation resulted from S. aureus exposure is that
      chondrocytes initiates a self-protective responsiveness by producing more AMPs
      against bacterial infection. (c) 2017 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res 36:443-451, 2018.

PMID- 28513982
TI  - Plasmon Enhanced Fluorescence Based on Porphyrin-Peptoid Hybridized Gold
      Nanoparticle Platform.
AB  - A porphyrin-peptoid-hybridized silica-coated gold nanoparticle is developed,
      which is inspired by the protein-chlorophyll ensemble found in photosynthetic
      antenna. In the natural antenna, chlorophylls are integrated into dense
      assemblies that are supported by frameworks of proteins, which ensure optimal
      pigment arrangement for effective light harvesting. In the subject platform,
      porphyrins are conjugated to the peptoid helix scaffold in a structurally well
      defined alignments and subsequently immobilized on the surface of nanoparticles.
      This prevents intermolecular aggregation among porphyrins and allows high
      resolution analysis of the effect of porphyrin configuration on the optical
      properties of the system. Interestingly, under the influence of plasmon from the
      gold nanoparticle core, the fluorescence of porphyrin is enhanced up to 24-fold
      at the wavelength where the plasmon resonance matches the porphyrin excitation
      wavelength. In addition, differences in porphyrin configuration result in
      spectral modification of their fluorescence emissions. Particularly, the peptoid
      bearing two porphyrins at a distance of 6 A shows the most significant alteration
      in fluorescence. The platform can facilitate extensive studies on the
      relationship between porphyrin arrangement design and their photophysical
      interaction in antenna complexes.

PMID- 28513984
TI  - sPD-L1 Expression is Associated with Immunosuppression and Infectious
      Complications in Patients with Acute Pancreatitis.
AB  - Acute pancreatitis (AP) with infectious complications has high mortality because
      of early-stage immunosuppression. The programmed cell death-1 (PD-1)/programmed
      cell death ligand 1 (PD-L1) pathway is an important host immunosuppression
      mechanism. Soluble PD-L1 (sPD-L1) expression regulates co-inhibitory signals in
      malignancies or autoimmune disorders; however, its effects in AP are unknown.
      Here, we evaluated whether serum sPD-L1 is involved in immune dysfunction and
      assessed its relationship with infectious complications in early AP. Blood
      samples were obtained from 56 patients with acute pancreatitis and 21 healthy
      individuals in this prospective study. Serum sPD-L1 levels within 48 h after AP
      onset were tested by enzyme-linked immunosorbent assays. Relevant immune
      parameters (human leucocyte antigen-DR, lymphocyte count) and inflammatory
      markers (C-reactive protein, white blood cell count) were analysed. sPD-L1 was
      significantly upregulated in patients with early AP, especially those with
      infectious complications, compared to healthy controls. Significant negative
      correlations were observed among monocyte HLA-DR expression, lymphocyte count and
      sPD-L1 levels in AP. Multivariate regression indicated that sPD-L1 was an
      independent risk factor for infectious complications in AP. The findings suggest
      that increased sPD-L1 expression appears to be involved in the development of
      immunosuppression in the early stage of AP and that sPD-L1 might be an early
      parameter for prediction of infectious complications in patients with AP.

PMID- 28513986
TI  - Pleiotropic Effects of Chronic Phorbol Ester Treatment to Improve Glucose
      Transport in Insulin-Resistant Cardiomyocytes.
AB  - Stimulation of glucose transport is an important determinant of myocardial
      susceptibility to ischemia and reperfusion. Stimulation of glucose transport is
      markedly impaired in cardiomyocytes exposed to free fatty acids (FFA).
      Deactivation of the Focal Adhesion Kinase (FAK) by FFA contributes to glucose
      transport impairment, and could be corrected by chronic treatment with the
      phorbol ester TPA. However, TPA must have effects in addition to FAK reactivation
      to restore stimulated glucose transport. Chronic treatment with TPA improved
      basal and stimulated glucose transport in FFA-exposed, but not in control
      cardiomyocytes. Chronic FFA exposure induced the activation of PKCdelta and
      PKCepsilon. TPA markedly downregulated the expression of PKCalpha, PKCdelta, and
      PKCepsilon, suggesting that PKCdelta or PKCepsilon activation could contribute to
      inhibition of glucose transport by FFA. Rottlerin, a specific PKCdelta inhibitor,
      improved glucose transport in FFA-exposed cardiomyocytes; and PKCdelta was
      reduced in the particulate fraction of FFA + TPA-exposed cardiomyocytes. TPA also
      activated Protein Kinase D 1(PKD1) in FFA-exposed cardiomyocytes, as assessed by
      autophosphorylation of PKD1 on Y916. Pharmaceutical inhibition of PKD1 only
      partially prevented the improvement of glucose transport by TPA. Chronic TPA
      treatment also increased basal and stimulated glycolysis and favored accumulation
      of lipid droplets in FFA-exposed cardiomyocytes. In conclusion, basal and
      stimulated glucose transport in cardiomyocytes is reduced by chronic FFA
      exposure, but restored by concomitant treatment with a phorbol ester. The
      mechanism of action of phorbol esters may involve downregulation of PKCdelta,
      activation of PKD1 and a general switch from fatty acid to glucose metabolism. J.
      Cell. Biochem. 9999: 4716-4727, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513985
TI  - Self-assembled nanofiber coatings for controlling cell responses.
AB  - Nanofibers are thought to enhance cell adhesion, growth, and function. We
      demonstrate that the choice of building blocks in self-assembling nanofiber
      systems can be used to control cell behavior. The use of 2 D-coated, self
      assembled nanofibers in controlling lens epithelial cells, fibroblasts, and
      mesenchymal stem cells was investigated, focusing on gene and protein expression
      related to the fibrotic response. To this end, three nanofibers with different
      characteristics (morphology, topography, and wettability) were compared with two
      standard materials frequently used in culturing cells, TCPS, and a collagen type
      I coating. Cell metabolic activity, cell morphology, and gene and protein
      expression were analyzed. The most hydrophilic nanofiber with more compact
      network consisting of small fibers proved to provide a beneficial 2 D environment
      for cell proliferation and matrix formation while decreasing the fibrotic/stress
      behavior in all cell lines when compared with TCPS and the collagen type I
      coating. This nanofiber demonstrates the potential to be used as a biomimetic
      coating to study the development of fibrosis through epithelial-to-mesenchymal
      transition. This study also shows that nanofiber structures do not enhance cell
      function by definition, because the physico-chemical characteristics of the
      nanofibers influence cell behavior as well and actually can be used to regulate
      cell behavior toward suboptimal performance. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 105A: 2252-2265, 2017.

PMID- 28513987
TI  - Dermatological diseases in palliative care patients: a prospective study of 271
      patients.
AB  - BACKGROUND: Numerous risk factors place palliative care patients at an increased
      risk of skin infections, dermatitis, and pressure sores. Furthermore, worsening
      of chronic skin disorders can be expected, as well as the development of
      treatment-induced and malignancy-related dermatoses. The objective of the present
      study was to investigate the prevalence and treatment of dermatological
      conditions in patients receiving hospital-based palliative care. METHODS: Two
      hundred seventy-one palliative patients were enrolled. All assessments were
      conducted by dermatologists. Skin lesions were classified into seven categories:
      infections, skin tumors, dermatitis, chronic wounds, nail and hair disorders,
      pruritus, and other unclassified conditions. Treatment modalities were classified
      as topical only or systemic. RESULTS: Overall, 1,267 dermatological conditions
      were recorded, 49 % of which were hospital-acquired. All patients had at least
      one dermatological condition, and more than 50 different dermatological disorders
      were noted. The most common group of skin disorders was dermatitis (18.3 % of all
      dermatological conditions), followed by nail and hair disorders (17.5 %). Almost
      16 % of dermatological conditions were treated systemically. CONCLUSIONS:
      Dermatological conditions are a common and clinically significant problem for
      palliative patients. The inclusion of dermatologists in multidisciplinary
      palliative teams should prove helpful in the management of these patients.

PMID- 28513988
TI  - Aquagenic cutaneous disorders.
AB  - Aquagenic cutaneous disorders, which include aquagenic urticaria, aquagenic
      pruritus, and aquagenic acrokeratoderma, are a group of rare diseases
      characterized by skin lesions or discomfort induced by brief contact with water.
      Aquagenic urticaria is characterized by pruritic wheals that occur at the sites
      of water contact, either immediately or within minutes, and disappear within 30
      60 min after water removal. Aquagenic pruritus presents with severe pruritus or a
      stinging, tingling, or burning sensation without any visible skin changes. These
      symptoms occur immediately or within minutes after the skin is exposed to water,
      lasting for one hour or longer. Aquagenic acrokeratoderma usually presents with
      whitish papules and plaques, edema, and hyperwrinkling within 2-20 min after
      brief exposure to water; symptoms disappear within minutes to one hour after
      drying. The pathomechanisms of these diseases are not yet fully understood, and
      their diagnosis is primarily based on clinical features. Treatment remains a
      challenge. Herein, we review the literature regarding these unusual disorders.

PMID- 28513989
TI  - Graphene/dodecanol floating solidification microextraction for the
      preconcentration of trace levels of cinnamic acid derivatives in traditional
      Chinese medicines.
AB  - A novel graphene/dodecanol floating solidification microextraction followed by
      HPLC with diode-array detection has been developed to extract trace levels of
      four cinnamic acid derivatives in traditional Chinese medicines. Several
      parameters affecting the performance were investigated and optimized. Also,
      possible microextraction mechanism was analyzed and discussed. Under the optimum
      conditions (amount of graphene in dodecanol: 0.25 mg/mL; volume of extraction
      phase: 70 MUL; pH of sample phase: 3; extraction time: 30  min; stirring rate:
      1000 rpm; salt amount: 26.5% NaCl; volume of sample phase: 10 mL, and without
      dispersant addition), the enrichment factors of four cinnamic acid derivatives
      ranged from 26 to 112, the linear ranges were 1.0 * 10-2 -10.0 MUg/mL for caffeic
      acid, 1.3 * 10-3 -1.9 MUg/mL for p-hydroxycinnamic acid, 2.8 * 10-3 -4.1 MUg/mL
      for ferulic acid, and 2.7 * 10-3 -4.1 MUg/mL for cinnamic acid, with r2 >=
      0.9993. The detection limits were found to be in the range of 0.1-1.0 ng/mL, and
      satisfactory recoveries (92.5-111.2%) and precisions (RSDs 1.1-9.5%) were also
      achieved. The results showed that the approach is simple, effective and sensitive
      for the preconcentration and determination of trace levels of cinnamic acid
      derivatives in Chinese medicines. The proposed method was compared with
      conventional dodecanol floating solidification microextraction and other
      extraction methods.

PMID- 28513990
TI  - Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene
      Mutations on Overall Survival of Breast Cancer Based on TCGA Database.
AB  - The study was conducted for comparing the effects of 12 DNA damage response gene
      mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1,
      and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We
      searched the Cancer Genome Atlas (TCGA) database from inception to September
      2016. Studies that investigated the association between 12 DNA damage responses
      related genes and BC consolidated into this Network meta-analysis, by comparing
      directly or indirectly to evaluate the hazard rate (HR) value and the surface
      under the cumulative sequence ranking curves (SUCRA). In total four articles were
      involved. Our results demonstrated 12 DNA damage response gene mutations were
      associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6
      26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0;
      BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR =
      11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI =
      2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0;
      PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA
      results revealed that the mutation of MDC1 gene was related to the worst
      prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene
      mutations were associated to the poor prognosis in patients with BC and the BC
      patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118:
      4728-4734, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28513992
TI  - Immunoregulatory protein B7-H3 promotes growth and decreases sensitivity to
      therapy in metastatic melanoma cells.
AB  - B7-H3 (CD276) belongs to the B7 family of immunoregulatory proteins and has been
      implicated in cancer progression and metastasis. In this study, we found that
      metastatic melanoma cells with knockdown expression of B7-H3 showed modest
      decrease in proliferation and glycolytic capacity and were more sensitive to
      dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP
      kinase (MAPK) and AKT/mTOR pathways: vemurafenib (PLX4032; BRAF inhibitor),
      binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor), and
      triciribidine (API-2; AKT inhibitor). Similar effects were observed in melanoma
      cells in the presence of an inhibitory B7-H3 monoclonal antibody, while the
      opposite was seen in B7-H3-overexpressing cells. Further, combining B7-H3
      inhibition with small-molecule inhibitors resulted in significantly increased
      antiproliferative effect in melanoma cells, as well as in BRAFV600E mutated cell
      lines derived from patient biopsies. Our findings indicate that targeting B7-H3
      may be a novel alternative to improve current therapy of metastatic melanoma.

PMID- 28513991
TI  - Immunoprotective Effect of Chitosan Particles on Hymenolepis nana - Infected
      Mice.
AB  - Hymenolepis nana is the most commonly known intestinal cestode infecting mainly
      human. This study aimed to investigate the potential effect of chitosan particles
      (CSP) to enhance the immune system against H. nana infection. Determination of
      worm burden, egg output, histopathological changes, oxidative stress markers
      (lipid peroxidation and reduced glutathione), goblet (GCs) and mucosal mast cells
      (MMCs) counts in intestinal ileum was performed. In addition, levels of
      intestinal mRNA expression of interleukin (IL)-4, IL-9, stem cell factor (SCF),
      type I and II interferons (IFN)-alpha/ gamma, tumour necrosis factor (TNF)-alpha,
      mucin 2 (MUC2) and inducible nitric oxide synthase (iNOs) were investigated using
      real-time PCR. The results indicated induced reductions in adult worm and egg
      counts in infected mice after CSP treatment. This was associated with improvement
      in tissue morphometric measurements and oxidative stress which were altered after
      infection. Expression levels of iNOs, IFN-alpha, IFN-gamma, TNF-alpha and IL-9
      were decreased by CSP. Conversely, expression levels of MUC2, IL-4 and SCF
      increased compared to infected untreated group. In addition, GCs and MMCs counts
      were normalized by CSP. In conclusion, this study could indicate the
      immunoprotective effect of CSP against H. nana infection. This was characterized
      with Th2 anti-inflammatory responses.

PMID- 28513993
TI  - Patient reported outcomes in orthopaedics.
AB  - Patient reported outcome measures (PROMs) are key tools when performing clinical
      research and PROM data are increasingly used to inform clinical decision-making,
      patient-centered care, health policy and more recently, reimbursement decisions.
      PROMs must possess particular properties before they are used. Thus purpose of
      this paper is to give an overview of PROMs, their definition, how their evidence
      can be assessed, how they should be reported in clinical research, how to choose
      PROMs, the types of PROMs available in orthopaedics, where these measures can be
      found, PROMs in orthopaedic clinical practice and what are some key next steps in
      this field. If PROMs are used in accordance with the guidance in this article, I
      believe we will gain considerable insight into PROMs in orthopaedics and will
      advance this field in a way that can contribute to science, improve patient care
      and save considerable resources. (c) 2017 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 35:2098-2108, 2017.

PMID- 28513994
TI  - Ultrahigh-Conductivity Polymer Hydrogels with Arbitrary Structures.
AB  - A poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) hydrogel
      is prepared by thermal treatment of a commercial PEDOT:PSS (PH1000) suspension in
      0.1 mol L-1 sulfuric acid followed by partially removing its PSS component with
      concentrated sulfuric acid. This hydrogel has a low solid content of 4% (by
      weight) and an extremely high conductivity of 880 S m-1 . It can be fabricated
      into different shapes such as films, fibers, and columns with arbitrary sizes for
      practical applications. A highly conductive and mechanically strong porous fiber
      is prepared by drying PEDOT:PSS hydrogel fiber to fabricate a current-collector
      free solid-state flexible supercapacitor. This fiber supercapacitor delivers a
      volumetric capacitance as high as 202 F cm-3 at 0.54 A cm-3 with an extraordinary
      high-rate performance. It also shows excellent electrochemical stability and high
      flexibility, promising for the application as wearable energy-storage devices.

PMID- 28513995
TI  - Inner strength and its relationship to health threats in ageing-A cross-sectional
      study among community-dwelling older women.
AB  - AIM: To explore the relationship between inner strength and health threats among
      community-dwelling older women. BACKGROUND: Inner strength is described as a
      resource that promotes experiences of health, despite adversities. Inner strength
      and its dimensions (i.e. connectedness, creativity, firmness and flexibility) can
      be assessed using the Inner Strength Scale (ISS). Exploring attributes of weaker
      inner strength may yield valuable information about areas to focus on in
      enhancing a person's inner strength and may ultimately lead to the perception of
      better health. DESIGN: Cross-sectional questionnaire survey. METHODS: The study
      is based on responses from 1270 community-dwelling older women aged 65 years and
      older; these were collected in the year 2010 and describe the situation that
      still exists today for older women. The questionnaire included the ISS,
      background characteristics and explanatory variables known to be health threats
      in ageing. Data were analysed using descriptive and inferential statistics.
      RESULTS: Poorer mental health was related to weaker inner strength in total and
      in all the dimensions. Symptoms of depressive disorders and feeling lonely were
      related to three of the dimensions, except firmness and creativity respectively.
      Furthermore, poor physical health was associated with the dimensions firmness and
      flexibility. Other health threats were significantly related to only one of the
      dimensions, or not associated at all. CONCLUSION: Mental ill health has overall
      the strongest association with weaker inner strength. Longitudinal studies are
      recommended to confirm the results. However, the ISS does not only estimate inner
      strength but can also be a tool for discovering where (i.e. dimension)
      interventions may be most profitable.

PMID- 28513996
TI  - Conformational Dynamics of mRNA in Gene Expression as New Pharmaceutical Target.
AB  - Gene expression involves concurrent and consecutive events of unidirectional
      nature, such as transcription occurring from 5' to 3' end and translation from N
      to C terminus. Recent functional studies have shown the importance of kinetically
      coupled nucleic acid folding events that influence gene expression processes. For
      example, mRNA conformational dynamics during transcription and translation
      regulate gene expression and subsequent protein functionalization. The structure,
      stability, and kinetic properties of nucleic acids are sensitive to the
      intracellular molecular environment and can be regulated by using artificially
      developed molecules. Here, we review our current understanding of how mRNA
      conformational dynamics affect the consecutive and concurrent processes involved
      in gene expression and discuss how novel pharmaceutical agents designed to
      influence RNA conformational dynamics, could be developed to treat various
      diseases.

PMID- 28513997
TI  - Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA.
AB  - Anchoring DNA via hydrophobic units into the membrane of vesicles allows tagging
      of these nanocontainers with sequence information. Moreover, the hybridization of
      DNA on the surface of liposomes enables sequence specific functionalization,
      vesicle aggregation, and vesicle fusion. Specifically, DNA-hybridization-based
      approaches for fusion employing oligonucleotides terminally modified with one or
      two anchoring units were hindered by a limited degree of full fusion or by
      significant leakage during fusion. The current work deals with a new strategy for
      anchoring oligonucleotides on a membrane by lipid-modified nucleobases rather
      than by attaching hydrophobic units to the 3'- or 5'-termini. The lipid anchors
      were incorporated into the DNA sequence via phosphoramidite nucleotide building
      blocks during automated solid-phase synthesis allowing variation of the number
      and position of hydrophobic units along the DNA backbone. Single-stranded DNA
      functionalized with four lipid-modified nucleobases was stably grafted onto the
      membrane of lipid vesicles. It was found that the orientation of DNA
      hybridization and the number of anchoring units play a crucial role in liposomal
      fusion, which in the most efficient system reached remarkable 29 % content mixing
      without notable leakage.

PMID- 28513998
TI  - Inflammatory bowel disease caused by primary immunodeficiencies-Clinical
      presentations, review of literature, and proposal of a rational diagnostic
      algorithm.
AB  - Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative
      colitis have a multifactorial pathogenesis with complex interactions between
      polygenetic predispositions and environmental factors. However, IBD can also be
      caused by monogenic diseases, such as primary immunodeficiencies (PID). Recently,
      an increasing number of these altogether rare diseases have been described to
      present often primarily, or solely, as IBD. Early recognition of these conditions
      enables adaption of therapies and thus directly benefits the course of IBDs.
      Here, we discuss the different clinical presentations in IBD and characteristic
      features of patient's history, clinical findings, and diagnostic results
      indicative for a causative PID. Possible predictors are early onset of disease,
      necessity of parenteral nutrition, failure to respond to standard
      immunosuppressive therapy, parental consanguinity, increased susceptibility for
      infections, certain histopathologic findings, and blood tests that are atypical
      for classic IBD. We illustrate this with exemplary case studies of IBD due to
      NEMO deficiency, chronic granulomatous disease, common variable immunodeficiency,
      CTLA-4 and LRBA deficiency. Taking these factors into account, we propose a
      diagnostic pathway to enable early diagnosis of IBD due to PID.

PMID- 28513999
TI  - Microparticles of healthy origins improve endothelial progenitor cell dysfunction
      via microRNA transfer in an atherosclerotic hamster model.
AB  - AIM: In this study, we aimed: (i) to obtain and functionally characterize the
      cultures of late endothelial progenitor cells (EPCs) from the animal blood; (ii)
      to investigate the potential beneficial effects of circulating microparticles
      (MPs) of healthy origins on EPC dysfunctionality in atherosclerosis as well as
      involved mechanisms. METHODS: Late EPCs were obtained and expanded in culture
      from peripheral blood isolated from two animal groups: hypertensive
      hyperlipidaemic (HH) and control (C) hamsters. In parallel experiments, late EPC
      cultures from HH were incubated with MPs from C group. RESULTS: The results
      showed that late EPCs display endothelial cell phenotype: (i) have ability to
      uptake 1,1-dioctadecyl-3,3,3,3 tetramethylindocarbocyanine-labelled acetylated
      low-density lipoprotein and Ulex europaeus agglutinin lectin-1; (ii) express
      CD34, CD133, KDR, CD144, vWF, Tie-2. Late EPCs from HH exhibited different
      morphological and functional characteristics compared to control: (i) are smaller
      and irregular in shape; (ii) present decreased endothelial surface marker
      expression; (iii) display reduced proliferation, migration and adhesion; (iv)
      lose ability to organize themselves into tubular structures and integrate into
      vascular network; (v) have diminished function of inward rectifier potassium
      channels. The incubation of late EPCs with MPs improved EPC functionality by miR
      10a, miR-21, miR-126, miR-146a, miR-223 transfer and IGF-1 expression activation;
      the kinetic study of MP incorporation into EPCs demonstrated MP uptake by EPCs
      followed by the miRNA transfer. CONCLUSION: The data reveal that late EPCs from
      atherosclerotic model exhibit distinctive features and are dysfunctional, and
      their function recovery can be supported by MP ability to transfer miRNAs. These
      findings bring a new light on the vascular repair in atherosclerosis.

PMID- 28514001
TI  - Nutritional assessment of hospital patients: New methods and new opportunities.
AB  - Recently, two new methods (total body electrical conductivity [TOBEC] and
      bioelectrical impedance analysis [BIA]) have become available for the rapid,
      safe, and convenient estimation of total body water in hospital patients. Despite
      these clear advantages, the clinical usefulness of the TOBEC and BIA methods in
      patient diagnosis and care is likely to be restricted by illness-related changes
      in the hydration of the lean body and in the distribution of water between the
      intracellular and extracellular water compartments. If these methods can be
      refined so as to permit their measurement of extracellular water as rapidly as
      they now measure total body water, the ability of clinicians to assess and
      monitor the nutritional and metabolic status of their hospital patients will be
      greatly enhanced.

PMID- 28514002
TI  - Evidence for continuing secular increase in height within families in the United
      States.
AB  - Measures of mature heights of the second generation of longitudinal subjects in
      the Fels Institute growth study are now becoming available. When augmented by the
      heights of the parents who enrolled the first-generation children, these families
      provide three-generation data for mature height. Heights of the first-generation
      spouses are also available. The successive generations correspond approximately
      to the following birth cohorts: 1886-1920, 1921-1949, and 1950-1968. Also
      available in the Fels data are heights for two-generation families with parents
      and offspring in successive cohorts. In the three-generation families, the mean
      increases (cm) for 34 grandmothers, mothers, and daughters were 2.99 and 2.77,
      both significant with P < 0.01; for 14 grandfathers, fathers and sons, 3.15 and
      3.63, the latter significant with P < 0.05. In the first and second cohort two
      generation families, the mean increase for 67 mothers and daughters was 4.01 (P <
      0.01); for 62 fathers and sons, 3.84 (P < 0.01). In the second and third cohorts,
      the corresponding figures for 53 and 52 pairs were 3.00 and 4.36, both P < 0.01.
      In every case, the change in the rate of increase between the first and second
      generation cohort, and that between the second and third, was not statistically
      significant. There is no clear evidence that the secular increase in height is
      decreasing in these families. The finding must be qualified, however, by the
      observation that most of the first-generation subjects grew to maturity during
      the Great Depression, when nutrition may have suffered relative to that of the
      post-World War II years of the maturing second generation. Study of a third
      generation of Fels subjects may be necessary before a decrease in the secular
      trend becomes evident in this sample.

PMID- 28514000
TI  - Long-term outcomes and recurrence patterns of standard versus extended
      pancreatectomy for pancreatic head cancer: a multicenter prospective randomized
      controlled study.
AB  - BACKGROUND: Our previous randomized controlled trial revealed no difference in 2
      year overall survival (OS) between extended and standard resection for pancreatic
      adenocarcinoma. The present study evaluated the 5-year OS and recurrence patterns
      according to the extent of pancreatectomy. METHODS: Between 2006 and 2009, 169
      consecutive patients were prospectively enrolled and randomized to standard (n =
      83) or extended resection (n = 86) groups to compare 5-year OS rate, long-term
      recurrence patterns and factors associated with long-term survival. RESULTS: The
      surgical R0 rate was similar between the standard and extended groups (85.5 vs.
      90.7%, P = 0.300). Five-year OS (18.4 vs. 14.4%, P = 0.388), 5-year disease-free
      survival (14.8 vs. 14.0%, P = 0.531), and overall recurrence rates (74.7 vs.
      69.9%, P = 0.497) were not significantly different between the two groups,
      although the incidence of peritoneal seeding was higher in the extended group (25
      vs. 8.1%, P = 0.014). CONCLUSIONS: Extended pancreatectomy does not have better
      short-term and long-term survival outcomes, and shows similar R0 rates and
      overall recurrence rates compared with standard pancreatectomy. Extended
      pancreatectomy does not have to be performed routinely for all cases of
      resectable pancreatic adenocarcinoma, especially considering its associated
      increased morbidity shown in our previous study.

PMID- 28514004
TI  - Symposium in honor of Alex Roche.

PMID- 28514003
TI  - Statistical estimation of skeletal maturity.
AB  - Given a number of developing aspects of the skeletal system that may be used as
      indicators of maturity, some combination rule is required to produce a single
      numerical description of skeletal maturity from data on several such indicators.
      In the RWT system for estimation of skeletal maturity from indicators in the
      knee, a nonlinear statistical model for graded data is used for this purpose. In
      the application of a similar model in the FELS system for the hand-wrist, the
      estimation procedure was extended to include continuous as well as graded
      indicators. This paper describes the statistical estimation procedure used, with
      illustrations drawn from the hand-wrist system.

PMID- 28514005
TI  - Discussion.

PMID- 28514006
TI  - The FELS method of assessing the skeletal maturity of the hand-wrist.
AB  - The FELS method of assessing the skeletal maturity of the hand-wrist differs from
      the Greulich-Pyle and Tanner-Whitehouse methods in the observations made, the
      provision of a range of shapes to which maturity indicator grades can be assigned
      and in the statistical methods used to construct the scale of skeletal maturity.
      The FELS method for the hand-wrist was developed using 13,823 serial radiographs
      of the left hand-wrist of boys and girls in the Fels Longitudinal Study. One
      hundred-thirty possible indicators were originally identified. Eighty-five graded
      and 13 metric indicators were selected on the basis of an indicator's ability to
      discriminate between children at the same chronological age, its universal
      appearance, reliability, validity, and completeness. The subset of FEELS maturity
      indicators assessed at a chronological age are analyzed with a microcomputer
      program that provides the skeletal age and the standard error of the estimate for
      that skeletal age. Comparison among hand-wrist skeletal age assessments for
      children in the Fels Longitudinal Study by the FELS, Greulich-Pyle, and Tanner
      Whitehouse methods indicate that the FELS method is the more appropriate method
      for the present population of United States children.

PMID- 28514007
TI  - Maturity and its relationship to plasma lipid and lipoprotein levels in
      adolescents: The Fels longitudinal study.
AB  - During adolescence, changes in lipid and lipoprotein levels have been reported to
      be associated with changes in body composition and changes in endogenous
      testosterone and estradiol. These hormone levels are directly correlated with
      sexual and skeletal maturity levels. The purpose of the present study was to
      determine if there are associations during pubescence and adolescence,
      independent of chronological age, between measures of maturity and body
      composition or plasma lipid and lipoprotein cholesterols. Skeletal maturity was
      measured on the basis of skeletal assessments of the bones of the knee joint. Age
      at peak height velocity was determined from serial stature measurements and, in
      girls, age at menarche was recorded. These measures of maturity, as well as
      measures of percent body fat, total body fat, total body fat mass, fat-free mass
      from underwater weighing, and plasma cholesterol, triglyceride, highdensity
      lipoprotein-cholesterol, and low-density lipoprotein-cholesterol levels from 502
      observations on 174 boys and girls enrolled in the Fels Longitudinal Study were
      used in the analysis. Within annual chronological age groups, no associations
      were found between level of maturity and lipid and lipoprotein level or percent
      body fat in boys or girls. However, changes in lipid and lipoprotein levels over
      time appeared to be more apparent when age grouping were based on skeletal age
      than when they were based on chronological age.

PMID- 28514008
TI  - Resistant cross- age smoothing of age-specific percentiles for growth reference
      data.
AB  - Resistant delineation, a technique adapted from exploratory data analysis (Tukey,
      Exploratory Data Analysis, 1977), was applied to smooth age-specific percentiles
      for triceps skinfold thickness across ages from 1 to 20 years. Row percentiles
      were transformed to logarithms to promote symmetry and to render variability more
      nearly homogeneous across ages. The delineation involved smoothing resistantly
      the sequences of age-specific log medians and the sequence of age-specific
      positive differences between the "4253H, twice" (Velleman, J. Am. Statist.
      Assoc., 75:609-615, 1980). The delineation concluded by recombining these
      smoothed sequences to obtain smoothed percentiles in the log scale. Finally, the
      logarithmic transformation was reversed, yielding the smoothed age-specific
      percentiles. Comparisons of smoothed results from resistant, delineation with the
      original data indicated a satisfactory fit. Comparisons with published smoothed
      percentiles, obtained from the same data by a cubic-spline procedure, showed that
      the resistant delineation captured the structure of the raw data better than the
      cubic-spline procedure. The resistant delineation procedure makes few assumptions
      of the underlying data, it ensures a proper order relationship among the smoothed
      percentiles, it is relatively insensitive to isolated unusual data, and it is
      available in a common software package.

PMID- 28514009
TI  - Concept of chemical immaturity in body composition estimates: Implications for
      estimating the prevalence of obesity in childhood and youth.
AB  - This paper estimates the prevalence of obesity in 6-8-year-old children, 13-15
      year-old youth, and 18-19-old adults by using skinfold data of the National
      Nutrition and Health Examination Survey. Obesity is defined as above 25% fat in
      males and above 32% fat in females. Skinfold equations used to estimate the fat
      cotent at each age were based on a multicompontent approach that used body
      density, body water, and bone mineral. The prevalence of obesity in the U.S.
      population was found to be much lower in children than in youth and young adults
      and to increase from 1 in 20 in childhood to 1 in 5 in adulthood.

PMID- 28514010
TI  - Cohabitation, activity level, and energy intake in parent-child resemblance for
      selected biological traits.
AB  - Activity level and energy intake were estimated from 3-day records, including a
      weekend day, in parents and children from families of French descent.
      Subcutaneous fat from the summation of six skinfolds, fasting serum
      triglycerides, total and high-density lipoprotein cholesterol, and submaximal
      power output (PWC150 ) derived from a cycle ergometer test also were determined
      in these subjects. Dependent variables were normalized through log10 or squre
      root transformation, and scores were adjusted by generation for the effects of
      age and gender. Correlations with residual scores were performed with pairs of
      natural parents and child (N ? 1057) and pairs of foster parent and adopted child
      (N ? 283). Coefficients were generally little affected by statistical control
      over current activity level and energy intake. Pairs of biological relatives were
      classified as either very similar (25% of pairs) or very dissimilar (25% of
      pairs) in terms of energy intake or activity level. Correlations revealed that
      similarity or discordance in energy intake or activity level had only a slight
      effect on parent-child resemblance. In addition, duration of cohabitation had
      little influence on parent-child covariation. It was concluded that parent-child
      resemblance in subcutaneous fat, work capacity, and blood lipids are not
      significantly affected by current patterns of energy intake, activity level, or
      duration of cohabitation.

PMID- 28514011
TI  - Method for analyzing complex two-dimensional forms: Elliptical Fourier functions.
AB  - A generalized procedure, elliptical Fourier analysis, for accurately
      characterizing the shape of complex morphological forms of the type commonly
      encountered in the biological sciences, is described. Elliptical Fourier
      functions are derived as a parametric formulation from conventional Fourier
      analysis, i.e., as a pair of equations that are functions of a third variable.
      The use of elliptical Fourier functions circumvents three restrictions that have
      limited conventional Fourier analysis to certain classes of shapes. These
      restrictions are (1) equal divisions over the interval or period; (2) dependency
      on the coordinate system, i.e., conventional Fourier functions are not
      "coordinate free"; and (3) the presence of shapes with outlines that curve back
      on themselves, a common occurrence. These three limitations are effectively
      removed with the utilization of elliptical Fourier functions, facilitating the
      analysis of a much larger class of two-dimensional forms.

PMID- 28514012
TI  - Growth and maturity status of black and white children classified as obese by
      different criteria.
AB  - Weight, stature, bicondylar and biepicondylar breadths, estimated midarm muscle
      circumference, grip strength, and skeletal maturity were compared in 111 obese
      Black and 120 obese White children, 6 through 12 years of age. The children were
      classified as obese by the triceps skinfold (TSF), body mass index (BMI), or
      both, and were labeled, respectively as TSF Obese, BMI Obese, and BMI+TSF Obese.
      The anthropmetric dimensions, including grip strength, were transformed to z
      scores on the basis of age-, sex-, and race-specific means and standard
      deviations for a mixed longitudinal sample of children among whom the obese
      children were indentified. Skeletal maturityu was expressed as the diference
      between skeletal age (Tanner-Whitehouse II RUS method) and chronological age.
      Within each racial group, BMI+TSF Obese are heavier and taller, have larger
      extremity bone widths, have larger estimated midarm musculature, are stronger,
      and are more advanced in skeletal maturity than TSF Obese and average nonobese
      children. Although the number of children classified as BMI Obese is small, their
      apparently unique characteristic is an especially large estimated midarm muscle
      circumference compared to other obese children.

PMID- 28514015
TI  - Preparation of Mesoporous Basic Oxides through Assembly of Monodispersed Mg-Al
      Layered Double Hydroxide Nanoparticles.
AB  - Mesoporous basic Mg-Al mixed metal oxides (MMOs) with a high surface area and
      large pore size have been prepared through the assembly of monodispersed layered
      double hydroxide nanoparticles (LDHNPs) with block copolymer templates. The
      particle sizes of the LDHNPs were mainly controlled by varying the concentration
      of tris(hydroxymethyl)aminomethane (THAM), which was used as a surface
      stabilizing agent. LDHNPs and micelles of a block copolymer (Pluronic F127) were
      assembled to form a composite. The composites were calcined to transform them
      into mesoporous MMOs and to remove the templates. The Brunauer-Emmett-Teller
      surface areas, mesopore sizes, and pore volumes increased as a result of using
      the templates. Moreover, the pore sizes of the mesoporous MMOs could be
      controlled by using LDHNPs of different sizes. The mesoporous MMOs prepared from
      the LDHNPs showed much higher catalytic activity than a conventional MMO catalyst
      for the Knovenagel condensation of ethyl cyanoacetate with benzaldehyde. The
      mesoporous MMO catalyst prepared using the smallest LDHNPs, about 12 nm in size,
      showed the highest activity. Therefore, the use of monodispersed LDHNPs and
      templates is effective for preparing highly active mesoporous solid base
      catalysts.

PMID- 28514014
TI  - Repeatability of vessel density measurement in human skin by OCT-based
      microangiography.
AB  - PURPOSE: To investigate the repeatability of vessel density measurement at human
      arm skin in healthy subjects with OCT-based microangiography (OMAG). METHODS:
      Four locations including volar wrist, volar forearm, shoulder, and volar upper
      arm were scanned using an optimized swept source OCT system, working at center
      wavelength of 1300 nm and A-line rate of 100 kHz. Three scans were acquired at
      each location at the same visit. Vascular images of papillary dermis, reticular
      dermis, and the whole dermis layer were generated with OMAG processing and
      automatic segmentation algorithms. The vessel density (VD) of each layer was
      calculated based on vascular images, and the repeatability of the VD at the same
      physiological location was thereafter assessed. RESULTS: Fifteen healthy
      volunteers were included. High repeatability of VD was found for wrist, forearm,
      shoulder, and upper arm (coefficient of variation (CV)=2.4, 2.7, 2.7, 2.0, and
      intraclass correlation coefficient (ICC)=0.906, 0.854, 0.943, 0.916
      respectively). The VD measurements showed no significant difference between the
      four locations in any of the three layers, ie papillary layer (P=.1063),
      reticular layer (P=.3371), and whole dermis layer (P=.3233). CONCLUSION:
      Quantification of VD by using OCT/OMAG is repeatable when imaging skin tissue
      beds in healthy individuals.

PMID- 28514013
TI  - Antimicrobial Prescribing in Dogs and Cats in Australia: Results of the
      Australasian Infectious Disease Advisory Panel Survey.
AB  - BACKGROUND: Investigations of antimicrobial use in companion animals are limited.
      With the growing recognition of the need for improved antimicrobial stewardship,
      there is urgent need for more detailed understanding of the patterns of
      antimicrobial use in this sector. OBJECTIVES: To investigate antimicrobial use
      for medical and surgical conditions in dogs and cats by Australian veterinarians.
      METHODS: A cross-sectional study was performed over 4 months in 2011. Respondents
      were asked about their choices of antimicrobials for empirical therapy of
      diseases in dogs and cats, duration of therapy, and selection based on culture
      and susceptibility testing, for common conditions framed as case scenarios: 11
      medical, 2 surgical, and 8 dermatological. RESULTS: A total of 892 of the 1,029
      members of the Australian veterinary profession that completed the survey
      satisfied the selection criteria. Empirical antimicrobial therapy was more common
      for acute conditions (76%) than chronic conditions (24%). Overall, the most
      common antimicrobial classes were potentiated aminopenicillins (36%),
      fluoroquinolones (15%), first- and second-generation cephalosporins (14%), and
      tetracyclines (11%). Third-generation cephalosporins were more frequently used in
      cats (16%) compared to dogs (2%). Agreement with Australasian Infectious Disease
      Advisory Panel (AIDAP) guidelines (generated subsequently) was variable ranging
      from 0 to 69% between conditions. CONCLUSIONS AND CLINICAL IMPORTANCE: Choice of
      antimicrobials by Australian veterinary practitioners was generally appropriate,
      with relatively low use of drugs of high importance, except for the empirical use
      of fluoroquinolones in dogs, particularly for otitis externa and 3rd-generation
      cephalosporins in cats. Future surveys will determine whether introduction of the
      2013 AIDAP therapeutic guidelines has influenced prescribing habits.

PMID- 28514017
TI  - Isopimaric acid - a multi-targeting ion channel modulator reducing excitability
      and arrhythmicity in a spontaneously beating mouse atrial cell line.
AB  - AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it
      is not well controlled by present drugs. Because some resin acids open voltage
      gated potassium channels and reduce neuronal excitability, we explored the
      effects of the resin acid isopimaric acid (IPA) on action potentials and ion
      currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1
      cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25
      MUmol L-1 IPA reduced the action potential frequency by up to 50%. The effect of
      IPA on six different voltage-gated ion channels was investigated; most voltage
      dependent parameters of ion channel gating were shifted in the negative direction
      along the voltage axis, consistent with a hypothesis that a lipophilic and
      negatively charged compound binds to the lipid membrane close to the positively
      charged voltage sensor of the ion channels. The major finding was that IPA
      inactivated sodium channels and L- and T-type calcium channels and activated the
      rapidly activating potassium channel and the transient outward potassium channel.
      Computer simulations of IPA effects on all of the ion currents were consistent
      with a reduced excitability, and they also showed that effects on the Na channel
      played the largest role to reduce the action potential frequency. Finally,
      induced arrhythmia in the HL-1 cells was reversed by IPA. CONCLUSION: Low
      concentrations of IPA reduced the action potential frequency and restored regular
      firing by altering the voltage dependencies of several voltage-gated ion
      channels. These findings can form the basis for a new pharmacological strategy to
      treat atrial fibrillation.

PMID- 28514016
TI  - Self-Adjusting, Polymeric Multilayered Roll that can Keep the Shapes of the Blood
      Vessel Scaffolds during Biodegradation.
AB  - A self-adjusting, blood vessel-mimicking, multilayered tubular structure with two
      polymers, poly(epsilon-caprolactone) (PCL) and poly(dl-lactide-co-glycolide)
      (PLGA), can keep the shape of the scaffold during biodegradation. The inner (PCL)
      layer of the tube can expand whereas the outer (PLGA) layers will shrink to
      maintain the stability of the shape and the inner space of the tubular shape both
      in vitro and in vivo over months. This approach can be generally useful for
      making scaffolds that require the maintenance of a defined shape, based on FDA
      approved materials.

PMID- 28514018
TI  - Salvage of postcranioplasty implant exposure using free tissue transfer.
AB  - BACKGROUND: Refractory implant exposure is frustrating after cranioplasty. The
      purpose of this study was for the authors to present their experience with free
      tissue transfer for salvage of postcranioplasty implant exposure. METHODS: A
      retrospective medical chart review was conducted on all free tissue transfers
      performed for exposed implant coverage after cranioplasty between January 2004
      and February 2016. RESULTS: Twelve free flaps were performed in 11 patients who
      underwent postcranioplasty with implant exposure, and whose attempted implant
      coverage using locoregional flaps had failed. The free flaps used included
      anterolateral thigh flap, radial forearm flap, anteromedial thigh and rectus
      femoris chimeric flap, latissimus dorsi flap, gracilis flap, and Juri flap. The
      flap survival rate was 100%, and 10 of 11 implants (91%) were salvaged without
      removal. CONCLUSIONS: Free tissue transfer should be considered as the preferred
      reconstructive option for postcranioplasty exposed implant salvage. High rate of
      implant salvage (>90%) is possible even with chronic implant exposure (>3
      months).

PMID- 28514020
TI  - Work-related stress factors and problem drinking with special reference to
      measures of drinking.

PMID- 28514019
TI  - Does dust-associated pulmonary alveolar proteinosis represent an autoimmune
      disorder?
AB  - The role of autoantibodies against granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in the development of secondary pulmonary alveolar proteinosis
      (PAP) in patients exposed to occupational and environmental dust remains unclear.
      Herein, we describe two cases of secondary PAP who had GM-CSF antibodies and
      absence of STAT5 phosphorylation index, suggestive of a potential relationship
      between the appearance of GM-CSF antibodies and environmental dust exposure.
      However, whether the presence of GM-CSF antibodies is a part of the pathological
      process or represents an epiphenomenon is currently unknown. In this report, we
      would like to present two cases supporting these new data and briefly discuss the
      possible role of autoimmune mechanisms in the development of secondary PAP. Am.
      J. Ind. Med. 60:591-597, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28514022
TI  - One-year weight change and long-term sickness absence in professional
      firefighters.
AB  - BACKGROUND: Little is known about the association between weight change
      (particularly moderate weight loss, 5-10% in initial weight) and long-term
      sickness absence (LSA) in working populations. METHODS: Three hundred and forty
      professional firefighters reported their current and past (1 year ago) weights in
      a cross-sectional survey, along with their LSA experience due to a severe
      accident, injury, or illness during the previous 12 months. RESULTS: The
      prevalence of LSA was 14.7%. In the non-smoking male firefighters, the prevalence
      of LSA was 3.4% in those with moderate weight loss over the past year; 13.3% in
      those who maintained their weight; and 21.7% in those who gained their weight
      moderately: gamma coefficient, 0.44 (95%CI: 0.05, 0.66). The linear association
      remained significant after further controlling for age and alcohol consumption.
      And it was similar across the adiposity strata (normal weight, overweight, and
      obesity) of the firefighters 1 year ago. CONCLUSIONS: One-year weight loss was
      associated with decreased risk of LSA in professional firefighters.

PMID- 28514021
TI  - An update systematic review of fetal death, congenital anomalies, and fertility
      disorders among health care workers.
AB  - BACKGROUND: Health care workers (HCWs) are occupationally exposed to various
      hazards, some associated with adverse pregnancy outcomes in previous reviews.
      This systematic review aims at synthesizing the recent literature on occupational
      exposures among HCWs related to fetal death, congenital anomalies, and fertility
      disorders. METHODS: We searched the Medline database from 2000 to 2015 for
      articles about all potential occupational exposures of women and men working in
      this sector. RESULTS: We retained 32 studies, most of them (n = 30) among women
      HCWs. Studies based on job title reported excess risks of some congenital
      anomalies (especially nervous and musculoskeletal systems) among HCWs compared to
      non-HCWs but no evidence about fetal death. Excess risks associated with specific
      exposures includes reports of some congenital anomalies for women exposed to
      anesthetic gases. Exposure to some sterilizing agents and, with less evidence, to
      antineoplastic drugs and to ionizing radiation, is associated with increased
      risks of miscarriage but not stillbirth. Strenuous work schedules appear to be
      associated with fertility disorders, but the evidence is limited. Only a few
      studies have been published since 2000 about non-ionizing radiation, or about
      fertility disorders related to chemical or physical agents, or about male HCWs.
      CONCLUSIONS: Despite the establishment of recommendations to limit exposures of
      HCWs, some excess risks of adverse pregnancy outcomes are still reported and need
      to be explained.

PMID- 28514023
TI  - Silicosis prevalence and risk factors in semi-precious stone mining in Brazil.
AB  - BACKGROUND: Underground mining generates large amounts of dust and exposes
      workers to silica. This study aims to determine the prevalence and predictor
      factors for the development of silicosis among semi-precious-stone mineworkers in
      southern Brazil working in a self-administered cooperative. METHODS: In a cross
      sectional study of 348 current workers and retirees, demographic data, medical,
      and occupational history were collected through an interview performed by a nurse
      and medical record review. Risk factor associations were studied by Poisson
      multivariate regression. RESULTS: The overall prevalence of silicosis was 37%,
      while in current miners it was 28%. Several risk factors for silicosis were
      identified in the univariate analysis. Inadequate ventilation in the underground
      galleries combined with dry drilling, duration of silica exposure, and
      (inversely) education remained significant in the multivariate analysis (P <
      0.05). CONCLUSION: This study is unusual in studying semi-precious stone
      mineworkers in a self-administered worker cooperative with limited resources. The
      prevalence of silicosis was very high. A number of recommendations are made
      including technical support for worker cooperatives, surveillance of silica
      exposure and silicosis, exposure reduction measures, and benefits allowing
      impaired miners to leave the industry.

PMID- 28514024
TI  - Historical review of efforts to reduce noise-induced hearing loss in the United
      States.
AB  - BACKGROUND: Noise-induced hearing loss is a centuries-old problem that is still
      prevalent in the United States and worldwide. AIM: To describe highlights in the
      development of hearing loss prevention in the U.S. from World War II to the
      present. METHODS: Literature review. RESULTS: Approaches to occupational noise
      induced hearing loss prevention in the United States over the past seven decades
      are described using a hierarchy of controls framework and an interdisciplinary
      perspective. Historical timelines and developmental milestones related to
      occupational noise-induced hearing loss prevention are summarized as a life
      course. DISCUSSION: Lessons are drawn for other countries in their hearing
      conservation efforts. CONCLUSION: Future developments building on the hearing
      loss prevention work of the past 70 years can prevent the problem of occupational
      NIHL in the 21st century. Am. J. Ind. Med. 60:569-577, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28514026
TI  - Gambling with life: Masculinity, risk, and danger in the lives of unauthorized
      migrant roofers.
AB  - BACKGROUND: This paper examines the occupational experiences of unauthorized
      immigrants employed in one of the most dangerous occupations in the United
      States: roofing. METHODS: We draw on 40 in-depth interviews with return migrants
      in Guanajuato, Mexico, to examine how the adoption of masculinity, dangerous
      working conditions, the labor market structure, and absence of legal status
      exacerbates injuries for unauthorized roofers. FINDINGS: Undocumented men return
      to Mexico injured with chronic pain, health complications, and trauma. We find
      that men "do gender" that is adopt masculine beliefs, when they skirt safety
      practices, police each other's behaviors, withhold their emotions, experience
      heightened stress, and engage in poor health behaviors. It is a combination of
      dangerous working conditions, economic insecurity, and men seeking to fulfill
      their masculine roles that all combine to create unsafe working conditions and
      lead to injuries.

PMID- 28514027
TI  - Maximum oxygen consumption in marginally malnourished Colombian boys and girls 6
      16 years of age.
AB  - Treadmill measurements of maximum oxygen intake were made in 218 boys and 136
      girls 6-16 years of age who were classified as nutritionally normal or marginally
      malnourished. max (1. min-1 )increased with age, was lower in the undernourished
      than in the normal, and was significantly lower in girls than in boys. The sex
      differences persisted when max was expressed in terms of body weight and lean
      body mass, indicating that differences in physical activity between sexes may be
      the cause. The lower values of absolute max have implications for the productive
      ability of these children in heavy physical work when they are adults. When
      expressed in terms of body weight there are no major differences between
      Colombian and European children in the magnitude of their max values.

PMID- 28514025
TI  - Acute joint pain in the emerging green collar workforce: Evidence from the linked
      National Health Interview Survey and Occupational Information Network (O*NET).
AB  - BACKGROUND: Green jobs are a rapidly emerging category of very heterogeneous
      occupations that typically involve engagement with new technologies and changing
      job demands predisposing them to physical stressors that may contribute to the
      development of joint pain. METHODS: We estimated and compared the prevalence of
      self-reported acute (past 30 days) joint pain between green and non-green collar
      workers using pooled 2004-2012 National Health Interview Survey (NHIS) data
      linked to the Occupational Information Network Database (O*NET). RESULTS: Green
      collar workers have a higher prevalence of acute joint pain as compared to non
      green collar workers. Green collar workers with pain in the upper extremity
      joints were significantly greater than in the non-green collar workforce, for
      example, right shoulder [23.2% vs 21.1%], right elbow [13.7% vs 12.0%], left
      shoulder [20.1% vs 18.2%], and left elbow [12.0% vs 10.7%]. CONCLUSIONS: Acute
      joint pain reported by the emerging green collar workforce can assist in
      identifying at risk worker subgroups for musculoskeletal pain interventions.

PMID- 28514028
TI  - Clustering of cardiovascular risk factors in association with indices of
      adiposity and adipose tissue distribution in adults.
AB  - The hypothesis, that clustering of elevated levels of blood pressures, plasma
      lipids and lipoprotein cholesterols, and serum glucose in men and women was
      associated with indices of adiposity and adipose tissue distributione was tested
      while controlling for family membership, age, level of education, income, and
      smoking as well as menopause (surgical and natural )and the use of oral
      contraceptives and replacement estrogens in women. The study population included
      146 white men and 171 white women, 18-88 years of age, from 4 large kindreds
      residing in the Dayton, Ohio, metropolitan area. The data were collected between
      1977 and 1980 as part of a study of genetic factors in essentials hypertension.
      Four groups of individuals with similar levels for blood pressures, plasma lipids
      and lipoprotein cholesterols, and serum glucose were defined for each sex by
      using a k-means clustering algorithm. A group was identified in each sex that had
      higher than average values for all of these risk factors. Membership in this
      group was associated significantly with age and weight/stature2 in the men, and
      with age, weight/stature2 and the interaction of age and weight/stature2 in the
      women, after controlling for level of education, income, smoking, and, in the
      women, also for menopause, use of oral contraceptives, and replacement estrogens.
      Group membership was not associated significantly with family membership or with
      an index of adipose tissue distribution.

PMID- 28514030
TI  - Program of the 13th annual meeting of the Human Biology Council San Diego,
      California, April 4-6, 1989.

PMID- 28514029
TI  - Population decline in a Philippine Negrito hunter-gatherer society.
AB  - The Casiguran Agta constitute a Negrito hunter-gatherer society in northeastern
      Luzon. The hypothesis presented is that this population has suffered serious
      decline over the last half -century. Demographic data collected over a 24-year
      period are used to substantiate this hypothesis. Agta figures on crude death
      rate, rate of natural decrease, infant mortality, life expectancy at birth, and
      homicide are among the most extreme known for any human population. Reasons for
      this decline are described, with emphasis on the factor of homicide.

PMID- 28514031
TI  - Bylaws of the Human Biology Council.

PMID- 28514032
TI  - Longitudinal growth in height, weight, and bone age of Guatemalan Ladino and
      Indian schoolchildren.
AB  - Three longitudinal samples of Guatemalan schoolchildren are compared for amounts
      and rates of growth in height, weight, and bone age. The samples include children
      of two ethnic backgrounds: Ladinos, Spanish-speaking people of, generally,
      Western cultural orientation; and Indians, people of Mayan cultural descent. The
      Indians are of very low socioeconomic status (SES) and attend a public school in
      a rural village. The Ladinos come from two SES groups living in Guatemala City,
      one of high SES attending a private school and the other of low SES attending a
      public school. Graphical and statistical analyses show that for all samples of
      boys and girls there are generally, significant differences between samples (high
      SES>low SES>Indian) for amounts of growth in height, weight, and bone age. Boys
      show significant differences in rates of growth between samples, with the high
      SES sample growing more rapidly than the two low SES samples. Girls show
      significant differences in the rate of growth in height, but not in the rate of
      growth in weight or bone age. For Both boys and girls, rates of growth in height
      and weight differ more between samples than does rate of Skeltal development.
      These results demonstrate that (1) SES-related deficits in growth are cumulative
      during childhood and early adolescence, that (2) rates of growth for boys are,
      generally, more sensitive to the influence of SES than are the growth rates of
      girls, and that (3) childhood growth deficits of low SES children of low SES
      children are likely to carry over into adulthood.

PMID- 28514033
TI  - Implementation of Hills' growth curve analysis for unequal-time intervals using
      GAUSS.
AB  - Longitudinal data are widely regarded as the most efficient and informative type
      of data with which to investigate growth. Paradoxically, appropriate statistical
      methods for analyzing longitudinal data have been unavailable; with the exception
      of a computer program for executing Rao's (Biometrika 46:49-58, 1959) one-sample
      polynomial growth curve analysis (Schneiderman and Kowalski, Am. J. Phys.
      Anthropol. 67:323-333, 1985) and another applying the Preece-Baines function
      (Brown and Townsend, Ann. Hum. Biol. 9:495-505, 1982), no programs for analyzing
      longitudinal data are generally available to the scientific community. Whereas
      much of the pediatrically oriented work has involved fitting growth curves for
      individual children, the concern here is the estimation of growth trends for
      populations. An Adequate understanding of average tendencies is a prerequisite to
      understanding the growth of individuals. The present paper implements Hills'
      (Biometrics 24:189-196, 1968) analysis, which is formally equivalent to Rao's but
      uses finite differences instead of orthogonal polynomials. This method is
      suitable for data collected at unequal time points and generates explicit
      measures of velocity and acceleration. The polynomial specification of the curve
      that best fits the data is also determined with this method. An additional
      advantage of this approach is that it is conceptually simpler than the classic
      model of Rao. An application of this method is given using the same craniofacial
      growth data as in our earlier (1985) paper for comparability. We provide an easy
      to use program written in GAU's (Edlefson and Jones, Kent, WA; Applied Technical
      Systems, 1985), a matrix programming language that runs on PC-compatible
      microcomputers. This implementation for PCs extends the accessibility to
      investigators who may not have access to mainframe computers.

PMID- 28514034
TI  - Environmental influences cause menstrual synchrony, not pheromones.
AB  - To assess the influence of environmental conditions on the pattern of menstrual
      variation among women, data on menstrual cycles were recorded longitudinally from
      127 university women who lived in a group of houses surrounding a central
      courtyard. Adequate follow-up was available on 76 women, among whom menstrual
      synchrony occurred in a short period of time. During the first month of
      coresidence, the day of menstrual onset deviated from the mean by an average of
      13.7 days. During the next month, however, this average deviation declined to
      2.6days. Moreover, it was found that menstrual synchrony occurred in the overall
      sample regardless of the house of residence, although synchrony occurred to a
      greater extent in some houses than in others. It would thus appear that common
      environmental influences play an important role in the overall pattern of
      menstrual cyclicity.

PMID- 28514035
TI  - American Journal of Human Biology as the new official publication of the Human
      Biology Council.

PMID- 28514036
TI  - Validity of anthropometric regression equations for predicting changes in body
      fat of obese females.
AB  - The validity of ten popular anthropometric percent fat prediction equations for
      estimating changes in percentage of body fat for obese females was studied.
      Thirty-one obese females (mean +/- SEM, %fat = 36.7 +/- 1.1%, body mass = 75.6 +/
      1.7 kg, age = 32.8 +/- 1.1 years) participated in a diet-only, diet-plus
      exercise, or exercise-only program. Subjects lost 2.7 +/- 0.3 fat percentage
      points and 3.0 +/- 0.3 kg body mass during the 8-week study. While many of the
      equations had acceptable validity before and after body mass loss, when applied
      to the prediction of changes in body fat none of the equations was acceptable. It
      was concluded that use of anthropometric prediction equations to estimate
      individual percent fat change scores results in large errors and is not
      recommended.

PMID- 28514037
TI  - Socioeconomic correlates of fertility, mortality, and child survival in mothers
      from a disadvantaged, urban Guatemalan community.
AB  - Social and economic determinants of fertility, mortality, and child survival were
      studied in a sample of 519 mothers from EL Progreso, a disadvantaged community
      located on the outskirts of Guatemala city. Fertility (children ever-born) and
      mortality (number of children who had died postnatally) data were obtained from
      interviews, along with data on the characteristics of the mothers, fathers, and
      the households. Contraceptive use was recorded on a subsample of 167 mothers of 5
      year old children. Following factor analyses, three variables were selected for
      analysis: Years of schooling of the father and the mother and the type of fuel
      used for cooking. Father's education and type of fuel were significantly related
      to maternal fertility, while only the educational attainment of the mother was
      related to child mortality and survival. When contraceptive use was included in
      the ANCOVA in the subsample, it was a significant determinant of fertility, while
      father's education became nonsignificant. In terms of mortality, contraceptive
      use was a significant determinant, while the significance of the mother's
      education fell to a borderline value (P = 0.084).

PMID- 28514038
TI  - Editorial.

PMID- 28514039
TI  - Sexual maturation of Mexican-American adolescents.

PMID- 28514040
TI  - Salivary testosterone levels in males from the Ituri Forest of Zaire.
AB  - Morning and evening testosterone levels were measured in the saliva of Efe
      pygmies (N = 11) and Lese villagers (N = 18) living in the Ituri Forest of
      northeast Zaire and compared with levels in Boston controls (N = 10). With one
      exception, levels in the individual Zairois subjects fall within the normal
      ranges reported for Western clinical populations. Daily variation in the Zairois
      subjects (a.m./p.m. ratio = 1.32 for Efe, 1.22 for Lese) is also comparable to
      both the Boston controls (1.61) and values reported by other researchers for
      Western subjects. Average morning levels for the Zairois subjects (420 pmol/liter
      for Efe, 341 pmol/liter for Lese), however, fall significantly below the average
      for the Boston subjects (589 pmol/liter; Efe, P <0.05; Lese, P <0.01). A
      correlation between morning testosterone level and height is observed for the
      Lese sample (r=0.76, P <0.005). Similar correlations have not been reported for
      Western subjects. Possible roles of acute and chronic environmental conditions in
      generating these observations are noted. This study demonstrates the potential
      utility of salivary steroid assays for investigating questions related to male
      gonadal function under field conditions.

PMID- 28514041
TI  - Gynoid and android fat patterning in Japanese-American men: Body build and
      glucose metabolism.
AB  - Subcutaneous fat patterning was investigated in a sample of 229 second generation
      (Nisei) Japanese-American men enrolled in an epidemiological study of noninsulin
      dependent diabetes mellitus. The study sample consisted of 78 men with diabetes,
      72 with impaired glucose tolerance (IGT), and 79 with normal glucose tolerance,
      classified by a 75 gm oral glucose tolerance test(OGTT) and world Health
      Organization criteria. A combination of hierarchal cluster analysis and
      logarithmic regression analysis using skinfold thickness at seven anatomical
      sites yielded two distinctive fat pattern groups, viz, a gynoid fat pattern group
      (n = 16), with a significantly greater percentage of fat on the extremities; and
      an exaggerated android group (n = 34), with proportionately more fat on the trunk
      than predicted from total skinfold fat thickness. The two fat pattern groups and
      a sample of men of normal glucose tolerance (n = 53) were compared by analysis of
      variance with respect to 12 somatometric variables and indices encompassing
      length, breadth and muscle mass parameters. The three groups did not differ in
      age or height. In weight and body mass index, the gynoid fat pattern group was
      lowest, although there were no significant intergroup differences in total
      skinfold fat (seven sites summed). The gynoid group was also significantly less
      robust in body build than the android group, as judged by a lower intermembral
      index, lower ratios of bony chest breadth and biacromial diameter to sitting
      height, and reduced arm muscle mass. The prevalence of diabetes within each fat
      pattern group was slightly less than expected on the basis of the prevalence of
      IGT (44%) was found within the gynoid group; none of the differences were
      statistically significant. During the OGTT, the gynoid and android groups, minus
      diabetic men, differed significantly from men with normal glucose tolerance in
      serum glucose levels at 1.5 and 2 hr but not from one another. The limitations of
      cross-sectional data of this nature for determining a differential risk
      fordisorders of glucose metabolism associated with type of fat deposition are
      discussed.

PMID- 28514042
TI  - Effect of Crystallization Firing on Marginal Gap of CAD/CAM Fabricated Lithium
      Disilicate Crowns.
AB  - PURPOSE: To evaluate the marginal gaps of CAD/CAM (CEREC 3) produced crowns made
      from leucite-reinforced glass-ceramic (IPS Empress CAD) blocks (LG), and lithium
      disilicate (IPS e.max CAD) blocks before (LD-B), and after (LD-A) crystallization
      firing. MATERIALS AND METHODS: A human molar tooth (#19) was mounted with
      adjacent teeth on a typodont and prepared for a full-coverage ceramic crown. The
      typodont was assembled in the mannequin head to simulate clinical conditions.
      After tooth preparation 15 individual optical impressions were taken by the same
      operator using titanium dioxide powder and a CEREC 3 camera per manufacturer's
      instructions. One operator designed and machined the crowns in leucite-reinforced
      glass-ceramic blocks (n = 5) and lithium-disilicate blocks (n = 10) using the
      CEREC 3 system. The crowns were rigidly seated on the prepared tooth, and
      marginal gaps (MUm) were measured with an optical microscope (500*) at 12 points,
      3 on each of the M, B, D, and L surfaces of the leucite-reinforced glass-ceramic
      crowns and the lithium-disilicate crowns before and after crystallization firing.
      Results were analyzed by two-way ANOVA followed by a Tukey's post hoc multiple
      comparison test (alpha = 0.05). RESULTS: The overall mean marginal gaps (MUm) for
      the crowns evaluated were: LG = 49.2 +/- 5.5, LD-B = 42.9 +/- 12.2, and LD-A =
      57.2 +/- 16.0. The marginal gaps for LG and LD-B were not significantly
      different, but both were significantly less than for LD-A. CONCLUSIONS: The type
      of ceramic material did not affect the marginal gap of CAD/CAM crowns. The
      crystallization firing process required for lithium-disilicate crowns resulted in
      a significant increase in marginal gap size, likely due to shrinkage of the
      ceramic during the crystallization process. CLINICAL RELEVANCE: The marginal gap
      of CAD/CAM-fabricated lithium disilicate crowns increases following
      crystallization firing. The marginal gap still remains within clinically
      acceptable parameters.

PMID- 28514043
TI  - Factors affecting a face-to-face learning event.
AB  - BACKGROUND: Pharmacy professionals have multiple opportunities to attend learning
      events run by a series of providers. However, there has never been a large-scale
      evaluation of events. Currently, formats of learning sessions differ by provider
      with no optimum model identified. Pharmacy Education South London was formed in
      April 2014 for the provision of education and training for pharmacy professionals
      in South London, running sessions multiple times across various locations.
      OBJECTIVE: The objective of this work was to identify factors that influence the
      perceived success of a face-to-face supplementary education and training event
      from the perspective of attendees. METHODS: Evaluation forms from 600
      participants at training events followed by semi-structured individual interviews
      with 11 participants. KEY FINDINGS: Participants over 55 years were more likely
      to attend lecture style events versus those aged under 25 years who attended more
      workshops (P < 0.001); there was no correlation with gender. About 57.3% (n =
      344) of participants agreed fully that the event increased their understanding of
      the topics, although only 38.5% (n = 231) stated that it would change their
      practice. Themes influencing an event fell into three broad themes: personal
      reasons affecting attendance, success factors for the session and application of
      learning, all with related subthemes. Subthemes included commitments,
      convenience, awareness, topic and personal relevance, content and delivery and
      reference, review and action. CONCLUSIONS: In publicising events, the topic,
      including the driver for the topic and the skills that will be obtained, the
      speaker and their experience plus how learning can be applied after the event
      should be included.

PMID- 28514044
TI  - Specific Identification of Glycoproteins Bearing the Tn Antigen in Human Cells.
AB  - Glycoproteins contain a wealth of valuable information regarding the development
      and disease status of cells. In cancer cells, some glycans (such as the Tn
      antigen) are highly up-regulated, but this remains largely unknown for
      glycoproteins with a particular glycan. Herein, an innovative method combining
      enzymatic and chemical reactions was first designed to enrich glycoproteins with
      the Tn antigen. Using synthetic glycopeptides with O-GalNAc (the Tn antigen) or O
      GlcNAc, we demonstrated that the method is selective for glycopeptides with O
      GalNAc and can distinguish between these two modifications. The diagnostic ions
      from the tagged O-GalNAc further confirmed the effectiveness of the method and
      confidence in the identification of glycopeptides with the Tn antigen by mass
      spectrometry. Using this method, we identified 96 glycoproteins with the Tn
      antigen in Jurkat cells. The method can be extensively applied in biological and
      biomedical research.

PMID- 28514046
TI  - Systematic review: Early infant feeding practices and the risk of wheat allergy.
AB  - AIM: Wheat is a common allergen. Early feeding practices (breastfeeding,
      potentially allergenic foods) might affect the risk of allergy. To systematically
      evaluate the association between early feeding practices and the risk of wheat
      allergy and sensitisation. METHODS: Five databases were searched for studies of
      any design up to July 2015. RESULTS: We included seven studies (five
      observational, low to moderate quality, two randomised controlled trials (RCTs),
      high quality). The results come from observational studies unless stated
      otherwise. Longer breastfeeding was associated with wheat allergy (two studies, n
      = 1847) and sensitisation (one study, n = 3781). Evidence for exclusive
      breastfeeding was contradictory; longer exclusive breastfeeding was associated
      with either lower (one study, n = 408) or higher (one study, n = 3781) risk of
      wheat sensitisation. Breastfeeding at gluten introduction did not affect the risk
      of wheat allergy (two studies, n = 2581). Introducing cereal >=7 months of age
      increased the risk of wheat allergy (one study, n = 1612), but results from an
      RCT (n = 1303) showed no effect. Early introduction of gluten was associated with
      a reduced risk of wheat sensitisation up to 5 years in one observational study (n
      = 3781) but not in RCTs (n = 1303). CONCLUSIONS: Based on limited evidence, the
      influence of breastfeeding and an early exposure to gluten on the risk of wheat
      allergy remain uncertain. There is no evidence supporting breastfeeding at gluten
      introduction as modifying the risk. Early introduction of gluten might reduce the
      risk of sensitisation, but currently, no evidence exists that it affects the risk
      of wheat allergy.

PMID- 28514047
TI  - A Simplified Approach for Fabrication of a Lightweight Individualized Impression
      Tray with the Aid of Existing Obturator Prosthesis Using Lost Salt Technique.
AB  - Maxillary defects resulting from ablative oncologic surgery can be extensive and
      usually have complex contours. Impression procedures for such defects can be time
      consuming and cumbersome, challenging the skills of even the most-experienced
      clinician. A well-oriented impression tray with proper extension and adequate
      contour is essential for successfully capturing the relevant details in
      impression. This article describes a method using the patient's existing
      obturator prosthesis to simplify and expedite the fabrication of a lightweight
      individualized impression tray directly on an irreversible hydrocolloid
      impression, thus avoiding the preliminary impression procedure for the patient.

PMID- 28514045
TI  - Contrast Extravasation versus Hemorrhage after Thrombectomy in Patients with
      Acute Stroke.
AB  - BACKGROUND AND PURPOSE: Intra-arterial recanalization postprocedural imaging in
      stroke patients can result in diagnostic complications due to hyperdensities on
      noncontrast computed tomography (CT), which may represent either contrast
      extravasation or intracranial hemorrhage. If these lesions are hemorrhage, then
      they are risk factors becoming symptomatic, which, if not distinguished, can
      alter clinical management. We investigate the effects of iodinated contrast on
      postprocedural magnetic resonance imaging (MRI) and prevalence of equivocal
      imaging interpretations of postprocedural extravasated contrast versus hemorrhage
      while identifying protocol pitfalls. METHODS: We identified 10 patients diagnosed
      with ischemic stroke who underwent intra-arterial recanalization in a 5-year
      period. These patients demonstrated a hyperdensity on a postprocedural CT within
      24 hours, underwent an MRI within 48 hours, and an additional confirmatory
      noncontrast CT at least 72 hours postprocedure. RESULTS: Postprocedural MRI in
      all 10 stroke patients demonstrated T1 - and T2 -relaxation time changes due to
      residual iodine contrast agents. This lead to false positive postprocedural
      hemorrhage MRI interpretations in 2/10 patients, 3/10 false negative
      interpretations of contrast extravasation, and 5/10 equivocal interpretations
      suggesting extravasation or hemorrhage. Of these five cases, two were performed
      with gadolinium. CONCLUSION: MRI done within 48 hours postprocedure can lead to
      false positive hemorrhage or false negative contrast extravasation
      interpretations in stroke patients possibly due to effects from the administered
      angiographic contrast. Additionally, MRI should be done both after 72 hours for
      confirmation and without gadolinium contrast as the effects of the gadolinium
      contrast and residual angiographic contrast could lead to misdiagnosis.

PMID- 28514048
TI  - Carbon-Doped BN Nanosheets for the Oxidative Dehydrogenation of Ethylbenzene.
AB  - Carbon-based catalysts have demonstrated great potential for the aerobic
      oxidative dehydrogenation reaction (ODH). However, its widespread application is
      retarded by the unavoidable deactivation owing to the appearance of coking or
      combustion under ODH conditions. The synthesis and characterization of porous
      structure of BCN nanosheets as well as their application as a novel catalyst for
      ODH is reported. Such BCN nanosheets consist of hybridized, randomly distributed
      domains of h-BN and C phases, where C, B, and N were confirmed to covalent bond
      in the graphene-like layers. Our studies reveal that BCN exhibits both high
      activity and selectivity in oxidative dehydrogenation of ethylbenzene to styrene,
      as well as excellent oxidation resistance. The discovery of such a simple
      chemical process to synthesize highly active BCN allows the possibility of
      carbocatalysis to be explored.

PMID- 28514050
TI  - Photoredox-Controlled Mono- and Di-Multifluoroarylation of C(sp3 )-H Bonds with
      Aryl Fluorides.
AB  - A controllable mono- and di-multifluoroarylation of acyclic and cyclic N-aryl
      amines with aryl fluorides by photocatalyzed dual C(sp3 )-H/C(sp2 )-F
      functionalization has been developed, providing new access to a wide array of
      valuable alpha-fluoroarylated amines. In addition, the one-pot consecutive hetero
      di-multifluoroarylation of N-aryl pyrrolidines and N,N-dimethylanilines was
      achieved with high to excellent diastereoselectivity. This new defluorinative
      C(sp3 )-C(sp2 ) coupling is distinguished by a broad scope, good
      regioselectivity, and mild conditions as well as gram-scale and late-stage
      applicability, and thus constitutes a significant advance in the arylation of
      unactivated C(sp3 )-H bonds with aryl fluorides.

PMID- 28514049
TI  - Canine Cutaneous Plasmacytosis: 21 Cases (2005-2015).
AB  - BACKGROUND: Cutaneous plasmacytosis (CP) is a syndrome of multiple cutaneous
      plasma cell tumors, in the absence of multiple myeloma. Although rare in both
      humans and dogs, treatment recommendations are usually extrapolated from multiple
      myeloma protocols. To date, no case series of CP have been described in the
      veterinary literature. HYPOTHESIS/OBJECTIVES: To describe clinical presentation,
      determine treatment response rates and duration, and report overall survival of
      dogs with CP. ANIMALS: Twenty-one client-owned dogs with CP. METHODS: Medical
      records of 21 dogs with CP were reviewed. Diagnosis was based on histopathologic
      evaluation of at least 1 representative cutaneous or subcutaneous lesion in dogs
      with >=3 lesions. Dogs with suspicion of multiple myeloma were excluded. RESULTS:
      The most commonly affected breeds were the golden (5/21) and Labrador retriever
      (3/21). Fourteen of 21 dogs had >10 lesions, with some having >100. Lesions
      commonly were described as round, raised, pink-to-red, and variably alopecic or
      ulcerated. The most commonly used drug protocol was combined melphalan and
      prednisone, with an overall response rate (ORR) of 73.7% (14/19 dogs). Single
      agent lomustine was associated with a similar ORR of 71.4% (5/7 dogs). For all
      treatments combined, the median progression-free interval after the first
      treatment was 153 days. The median survival time from the first treatment was 542
      days. CONCLUSIONS AND CLINICAL IMPORTANCE: Alkylating agents were effective in
      inducing remission of CP; corticosteroids, melphalan, and lomustine were the most
      commonly used drugs. Survival times were similar to those reported in dogs with
      multiple myeloma treated with alkylating agents.

PMID- 28514052
TI  - Shift in community structure in an early-successional Mediterranean shrubland
      driven by long-term experimental warming and drought and natural extreme
      droughts.
AB  - Global warming and recurring drought are expected to accelerate water limitation
      for plant communities in semiarid Mediterranean ecosystems and produce
      directional shifts in structure and composition that are not easily detected, and
      supporting evidence is scarce. We conducted a long-term (17 years) nocturnal
      warming (+0.6 degrees C) and drought (-40% rainfall) experiments in an early
      successional Mediterranean shrubland to study the changes in community structure
      and composition, contrasting functional groups and dominant species, and the
      superimposed effects of natural extreme drought. Species richness decreased in
      both the warming and drought treatments. Responses to the moderate warming were
      associated with decreases in herb abundance, and responses to the drought were
      associated with decreases in both herb and shrub abundances. The drought also
      significantly decreased community diversity and evenness. Changes in abundance
      differed between herbs (decreases) and shrubs (increases or no changes). Both
      warming and drought, especially drought, increased the relative species richness
      and abundance of shrubs, favoring the establishment of shrubs. Both warming and
      drought produced significant shifts in plant community composition. Experimental
      warming shifted the community composition from Erica multiflora toward Rosmarinus
      officinalis, and drought consistently shifted the composition toward Globularia
      alypum. The responses in biodiversity (e.g., community biodiversity, changes of
      functional groups and compositional shifts) were also strongly correlated with
      atmospheric drought (SPEI) in winter-spring and/or summer, indicating sensitivity
      to water limitation in this early-successional Mediterranean ecosystem,
      especially to natural extreme droughts. Our results suggest that the shifts in
      species assembles and community diversity and composition are accelerated by the
      long-term nocturnal-warming and drought, combined with natural severe droughts,
      and that the magnitude of the impacts of climate change is also correlated with
      the successional status of ecosystem. The results thus highlight the necessity
      for assessing the impacts on ecosystemic functioning and services and developing
      effective measures for conserving biodiversity.

PMID- 28514053
TI  - A cluster randomized theory-guided oral hygiene trial in adolescents-A latent
      growth model.
AB  - OBJECTIVES: (i) To test whether theory-guided interventions are more effective
      than conventional dental instruction (CDI) for changing oral hygiene in
      adolescents and (ii) to examine whether such interventions equally benefit both
      genders and different socio-economic (SES) groups. METHODS: A total of 244
      adolescents were recruited from three schools, and cluster randomization
      allocated adolescents to one of the three types of interventions: two were theory
      based interventions (Precaution Adoption Process Model or Authoritative Parenting
      Model) and CDI served as an active control. Oral hygiene levels % (OH) were
      assessed at baseline, after 3 months and after 12 months. RESULTS: A complete
      data set was available for 166 adolescents (the total follow-up rate: 69%). There
      were no significant differences in baseline OH between those who participated
      throughout the study and those who dropped out. Bivariate and multivariate
      analyses showed that theory-guided interventions produced significant
      improvements in oral hygiene and that there were no significant gender or socio
      economic differences. CONCLUSIONS: Theory-guided interventions produced more
      positive changes in OH than CDI, and these changes did not differ between gender
      and SES groups.

PMID- 28514051
TI  - The PPARgamma-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on
      p21-mediated cellular senescence.
AB  - Cellular senescence is a permanent proliferative arrest triggered by genome
      instability or aberrant growth stresses, acting as a protective or even tumor
      suppressive mechanism. While several key aspects of gene regulation have been
      known to program this cessation of cell growth, the involvement of the epigenetic
      regulation has just emerged but remains largely unresolved. Using a systems
      approach that is based on targeted gene profiling, we uncovered known and novel
      chromatin modifiers with putative link to the senescent state of the cells. Among
      these, we identified SETD8 as a new target as well as a key regulator of the
      cellular senescence signaling. Knockdown of SETD8 triggered senescence induction
      in proliferative culture, irrespectively of the p53 status of the cells; ectopic
      expression of this epigenetic writer alleviated the extent doxorubicin-induced
      cellular senescence. This repressive effect of SETD8 in senescence was mediated
      by directly maintaining the silencing mark H4K20me1 at the locus of the
      senescence switch gene p21. Further in support of this regulatory link, depletion
      of p21 reversed this SETD8-mediated cellular senescence. Additionally, we found
      that PPARgamma acts upstream and regulates SETD8 expression in proliferating
      cells. Downregulation of PPARgamma coincided with the senescence induction, while
      its activation inhibited the progression of this process. Viewed together, our
      findings delineated a new epigenetic pathway through which the PPARgamma-SETD8
      axis directly silences p21 expression and consequently impinges on its senescence
      inducing function. This implies that SETD8 may be part of a cell proliferation
      checkpoint mechanism and has important implications in antitumor therapeutics.

PMID- 28514054
TI  - How do educators in one New Zealand undergraduate Bachelor of Oral Health course
      teach and nurture professionalism?
AB  - INTRODUCTION: Research on integrated dental hygiene and dental therapy courses is
      scarce; studies reporting on how staff in these combined scope courses teach
      professionalism are even more scarce. This study aimed to partially fill these
      research gaps. METHOD AND MATERIALS: In 2016, online surveys were sent to 34
      staff members who taught into the integrated Bachelor of Oral Health (BOH) course
      at the University of Otago's Faculty of Dentistry; 13 were returned. Two focus
      groups were conducted with six BOH educators. RESULTS: Aspects of professionalism
      were taught and nurtured in the formal curriculum, the clinic and the informal
      curriculum. In the formal curriculum, policies outlining the professional
      standards of behaviour expected of oral health practitioners and students in New
      Zealand and the Faculty were discussed. In the clinic, educators taught
      professionalism through modelling clinical skills, assessing students'
      performance and commenting on their reflective logbooks. In the informal
      curriculum, BOH teachers nurtured professionalism through discussions about
      standards of behaviour outside of the university. Role modelling was the most
      common method that participants reported they taught or nurtured professionalism
      in their students. DISCUSSION: Professionalism is a complex concept that is
      taught and nurtured in a number of ways over all aspects of the course.
      CONCLUSION: Oral Health educators need to maintain a high standard of
      professionalism when interacting with students and patients, as well as in public
      spaces, in order to model professionalism to their students.

PMID- 28514056
TI  - Ulcerative plaque within a tattoo in a 49-year-old man.

PMID- 28514057
TI  - High-performance liquid chromatographic cartridge with gradient elution
      capability coupled with UV absorbance detector and mass spectrometer for peptide
      and protein analysis.
AB  - We discuss the construction and performance of a high-performance liquid
      chromatography cartridge that we developed that resulted from a culmination of
      previous research. We have recently developed an innovative approach to creating
      gradient elutions using dual electroosmotic pumps and a series of three valves.
      This method has been proved to be the most reproducible and robust in producing
      gradients compared to our previously tested methods. Using this approach, we have
      assembled a high-performance liquid chromatography cartridge powered and
      controlled via a computer. We have successfully coupled the cartridge with an
      ultraviolet absorbance detector and a mass spectrometer for separating complex
      protein/peptide samples. The cartridge is readily coupled with other detectors
      such as electrochemical detector and laser-induced fluorescence detector.

PMID- 28514055
TI  - Caveolin-1 deficiency induces premature senescence with mitochondrial
      dysfunction.
AB  - Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1)
      during cellular senescence. For example, caveolin-1 deficiency prevents reactive
      oxygen species-induced cellular senescence despite mitochondrial dysfunction,
      which leads to senescence. To resolve this paradox, we re-addressed the role of
      caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and
      Cav-1-/- mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown)
      induced cellular senescence via a p53-p21-dependent pathway, downregulating the
      expression level of the cardiolipin biosynthesis enzymes and then reducing the
      content of cardiolipin, a critical lipid for mitochondrial respiration. Our
      results showed that Cav-1 deficiency decreased mitochondrial respiration, reduced
      the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and
      decreased the NAD+ /NADH ratio. From these results, we concluded that Cav-1
      deficiency induces premature senescence via mitochondrial dysfunction and silent
      information regulator 2 homologue 1 (SIRT1) inactivation.

PMID- 28514058
TI  - In Situ Observation of Crystallization of Methylammonium Lead Iodide Perovskite
      from Microdroplets.
AB  - It is of great importance to investigate the crystallization of organometallic
      perovskite from solution for enhancing performance of perovskite solar cells.
      Here, this study develops a facile method for in situ observation of
      crystallization and growth of the methylammonium lead iodide (MAPbI3 ) perovskite
      from microdroplets ejected by an alternating viscous and inertial force jetting
      method. It is found that there are two crystallization modes when MAPbI3 grows
      from the CH3 NH3 I (MAI)/PbI2 /N,N-dimethylformamide (DMF) solution: needle
      precursors and granular perovskites. Generally, needle Lewis adduct of MAPbI3
      .DMF tends to nucleate and grow from the solution due to low solubility of PbI2 .
      The growth of MAPbI3 .DMF depends on both the concentration of MAI and
      temperature. It tends to form large perovskite domains on substrates at high
      temperature. The MAPbI3 .DMF coverts to nanocrystalline perovskite due to lattice
      shrinkage when DMF molecules escape from the Lewis adduct. Granular perovskite
      can also directly nucleate from the solution at high concentration of MAI due to
      compositional segregation.

PMID- 28514059
TI  - [11 C]Fluoroform, a Breakthrough for Versatile Labeling of PET Radiotracer
      Trifluoromethyl Groups in High Molar Activity.
AB  - Positron-emission tomography (PET) is an immensely important imaging modality in
      biomedical research and drug development but must use selective radiotracers to
      achieve biochemical specificity. Such radiotracers are usually labeled with
      carbon-11 (t1/2 =20 min) or fluorine-18 (t1/2 =110 min), but these are only
      available from cyclotrons in a few simple chemical forms. [18 F]Fluoroform has
      emerged for labeling tracers in trifluoromethyl groups but is severely limited in
      utility by low radioactivity per mass (low molar activity). Here, the synthesis
      of [11 C]fluoroform is described, based on CoF3 -mediated fluorination of
      cyclotron-produced [11 C]methane. This process is efficient and repetitively
      reliable. [11 C]Fluoroform shows versatility for labeling small molecules in very
      high molar activity (>200 GBq MUmol-1 ), far exceeding that possible by using [18
      F]fluoroform. Therefore, [11 C]fluoroform represents a major breakthrough for
      labeling prospective PET tracers in trifluoromethyl groups at high molar
      activity.

PMID- 28514060
TI  - Improved in-tube electro-membrane extraction followed by high-performance liquid
      chromatography for simple and selective determination of ionic compounds:
      Optimization by central composite design.
AB  - In this work, an efficient sample clean-up method, named in-tube electro-membrane
      extraction, is modified to resolve the formation of bubbles in the extraction
      process. This modified method is applied for the extraction of two model analytes
      including tartrazine and sunset yellow from food samples. The method is based on
      the electro-kinetic migration of ionized compounds by the application of an
      electrical potential difference, and on this basis the analytes under
      investigation, as anionic compounds, simply migrate from the donor phase and
      concentrate in the acceptor phase. A thin polypropylene sheet placed in the tube
      acts as a support for the membrane solvent, and it separates 30 MUL of the
      aqueous acceptor from 1.2 mL of the aqueous donor. This setup can be used to
      solve the problem of extracting highly hydrophilic analytes. Response surface
      methodology is used for optimization of the experimental parameters so that under
      the optimized conditions, the method provides a good linearity in the range of 50
      1000 ng/mL, low limits of detection (15-25 ng/mL), good extraction
      repeatabilities (relative standard deviations below 8.1%, n = 5), and high
      extraction recoveries (54-76%).

PMID- 28514061
TI  - Mapping intermediate degradation products of poly(lactic-co-glycolic acid) in
      vitro.
AB  - There is widespread interest in using absorbable polymers, such as poly(lactic-co
      glycolic acid) (PLGA), as components in the design and manufacture of new
      generation drug eluting stents (DES). PLGA undergoes hydrolysis to progressively
      degrade through intermediate chemical entities to simple organic acids that are
      ultimately absorbed by the human body. Understanding the composition and
      structure of these intermediate degradation products is critical not only to
      elucidate polymer degradation pathways accurately, but also to assess the safety
      and performance of absorbable cardiovascular implants. However, analytical
      approaches to determining the intermediate degradation products have yet to be
      established and evaluated in a standard or regulatory setting. Hence, we
      developed a methodology using electrospray ionization mass spectrometry to
      qualitatively and quantitatively describe intermediate degradation products
      generated in vitro from two PLGA formulations commonly used in DES. Furthermore,
      we assessed the temporal evolution of these degradation products using time-lapse
      experiments. Our data demonstrated that PLGA degradation products via
      heterogeneous cleavage of ester bonds are modulated by multiple intrinsic and
      environmental factors, including polymer chemical composition, degradants
      solubility in water, and polymer synthesis process. We anticipate the
      methodologies and outcomes presented in this work will elevate the mechanistic
      understanding of comprehensive degradation profiles of absorbable polymeric
      devices, and facilitate the design and regulation of cardiovascular implants by
      supporting the assessments of the associated biological response to degradation
      products. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 1129-1137, 2018.

PMID- 28514063
TI  - Where are you heading? Flexible integration of retinal and extra-retinal cues
      during self-motion perception.
AB  - As we move forward in the environment, we experience a radial expansion of the
      retinal image, wherein the center corresponds to the instantaneous direction of
      self-motion. Humans can precisely perceive their heading direction even when the
      retinal motion is distorted by gaze shifts due to eye/body rotations. Previous
      studies have suggested that both retinal and extra-retinal strategies can
      compensate for the retinal image distortion. However, the relative contributions
      of each strategy remain unclear. To address this issue, we devised a two
      alternative-headings discrimination task, in which participants had either real
      or simulated pursuit eye movements. The two conditions had the same retinal input
      but either with or without extra-retinal eye movement signals. Thus, the
      behavioral difference between conditions served as a metric of extra-retinal
      contribution. We systematically and independently manipulated pursuit speed,
      heading speed, and the reliability of retinal signals. We found that the levels
      of extra-retinal contributions increased with increasing pursuit speed (stronger
      extra-retinal signal), and with decreasing heading speed (weaker retinal signal).
      In addition, extra-retinal contributions also increased as we corrupted retinal
      signals with noise. Our results revealed that the relative magnitude of retinal
      and extra-retinal contributions was not fixed but rather flexibly adjusted to
      each specific task condition. This task-dependent, flexible integration appears
      to take the form of a reliability-based weighting scheme that maximizes heading
      performance.

PMID- 28514065
TI  - Body size and form of black girls age 9 years living in central South Carolina
      and eastern North Carolina.
AB  - Somatic data were collected during 1986-1987 on 53 Black girls age 9 years living
      in Calhoun County in rural central South Carolina. Measures of body size
      (standing height, sitting height, upper limb length, lower limb height, arm
      girth, hip width, and body weight), body from (lower limb height as a percentage
      of sitting height, arm girth as a percentage of upper limb length, calf girth as
      a percentage of lower limb height, hip width as a percentage of lower limb
      height) and skin-fat thickness (over triceps and on abdomen) were analyzed for
      central tendency and variability. Comparisons were made with earlier samples of
      Black girls measured in rural regions of Richland County in central South
      Carolina during 1975-1976 and in urban Greenville city and rural Pitt County in
      eastern North Carolina during 1980-1981 as well as with earlier studies conducted
      in various parts of the United States. The four same-age group samples yielded
      similar means for standing height, sitting height, arm and calf girth, and body
      weight. The Calhoun County girls exceeded their Pitt County, North Carolina,
      peers in lower limb height, upper limb length, and lower limb height as a
      percentage of sitting height. In each of the subgroups studied, the distribution
      of measures for skin-fat thicknesses was, to some extent, skewed positively.

PMID- 28514064
TI  - Brain-Inspired Photonic Neuromorphic Devices using Photodynamic Amorphous Oxide
      Semiconductors and their Persistent Photoconductivity.
AB  - The combination of a neuromorphic architecture and photonic computing may open up
      a new era for computational systems owing to the possibility of attaining high
      bandwidths and the low-computation-power requirements. Here, the demonstration of
      photonic neuromorphic devices based on amorphous oxide semiconductors (AOSs) that
      mimic major synaptic functions, such as short-term memory/long-term memory, spike
      timing-dependent plasticity, and neural facilitation, is reported. The synaptic
      functions are successfully emulated using the inherent persistent
      photoconductivity (PPC) characteristic of AOSs. Systematic analysis of the
      dynamics of photogenerated carriers for various AOSs is carried out to understand
      the fundamental mechanisms underlying the photoinduced carrier-generation and
      relaxation behaviors, and to search for a proper channel material for photonic
      neuromorphic devices. It is found that the activation energy for the
      neutralization of ionized oxygen vacancies has a significant influence on the
      photocarrier-generation and time-variant recovery behaviors of AOSs, affecting
      the PPC behavior.

PMID- 28514062
TI  - Locoregional therapy with alpha-emitting trastuzumab against peritoneal
      metastasis of human epidermal growth factor receptor 2-positive gastric cancer in
      mice.
AB  - Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an
      extremely poor prognosis. We have found, however, that locoregionally
      administered trastuzumab armed with astatine-211 (211 At-trastuzumab) is
      effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC
      in a xenograft mouse model. We first observed that 211 At-trastuzumab can
      specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2
      positive human metastatic GC cells, both in vitro and in s.c. tumors. We
      established a PMGC mouse model using N87 xenografts stably expressing luciferase
      to test alpha-particle radioimmunotherapy with 211 At-trastuzumab against PMGC.
      Biodistribution analysis in this PMGC mouse model revealed that the i.p.
      administration of 211 At-trastuzumab (1 MBq) was a more efficient means of
      delivery of 211 At into metastatic tumors than i.v. injection; the maximum tumor
      uptake with i.p. administration was over 60% injected dose per gram of tissue
      (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a
      single i.p. injection of 211 At-trastuzumab (1 MBq) was sufficient to completely
      eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of
      six treated mice by inducing DNA double-strand breaks, and to drastically reduce
      the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or
      significant biochemical changes in liver or kidney function were observed in the
      treatment group. Accordingly, locoregionally administered 211 At-trastuzumab
      significantly prolonged the survival time of HER2-positive PMGC mice compared
      with control treatments. Our results provide a proof-of-concept demonstration
      that locoregional therapy with 211 At-trastuzumab may offer a new treatment
      option for HER2-positive PMGC.

PMID- 28514066
TI  - Raymond Pearl memorial lecture, 1988: Evolution of mitochondrial DNA in human and
      other organisms.
AB  - Within the last ten years complete sequencing of mitochondrial DNA in human and
      several other species, sequencing of nuclear and mitochondrial ribosomal and
      transfer RNAs in many species of bacteria, fungi, plants, and animals, and
      population studies of restriction enzyme polymorphism in the mtDNAs of insects,
      mammals and sixteen species of primates produced a wide range of new data and
      theory in molecular evolutionary genetics. These data support the endosymbiotic
      origin of the eukaryotic cell, the evolution of the Genus Homo with Pan as the
      closest related living genus, and the origin of modern Homo sapiens by
      gradualistic, anagenetic, regional phyletic transformation from Homo erectus.

PMID- 28514067
TI  - Fatness and fat distribution in Mexican-American children and youths from the
      Hispanic health and nutrition examination survey.
AB  - Mexican-American children are shorter but relatively heavier than non-Hispanic
      white children. The excess relative weight is probably due to increased fat
      rather than lean body mass and, more specifically, to increased fat deposition on
      the upper trunk sites. The objective of this paper is to describe the level of
      fatness and fat distribution in a large, representative sample of Mexican-
      American children and adolescents from the recently completed Hispanic Health and
      Nutrition Examination Survey (HHANES). As expected, Mexican-American children are
      generally fatter than white children measured in previous national surveys
      (National Health and Nutrition Examination Survey [NHANES] II, Health Examination
      Survey [HES]). Differences are particularly evident for trunk skinfold
      thicknesses and generally increase with age. Indices of fat distribution clearly
      show a centralized, upper body adiposity pattern among Mexican-Americans, a cause
      for concern since greater fat deposition on the trunk has been associated with
      increased risk of certain chronic disease.

PMID- 28514069
TI  - Introduction: Uses of molecular biology: Understanding the basis of genetic
      disease, determining evolutionary pathways, and other applications.

PMID- 28514068
TI  - DNA fingerprints in physical anthropology.
AB  - Hypervariabal minisatellite DNA is a recently described class of nuclear
      sequences with no known biological function. The minisatellites do form a subtype
      of restricition fragment length polymorphisms possessing several characteristics
      particularly intriguing to anthropologists interested in forensics, sociobiology,
      primate conservation, genetic variability, and molecular evolution. The sequence
      occupy at least five dozen loci scattered throughout the human genome. Unlike
      many polymorphisms, many of the loci have numerous alleles each present at
      similar frequencies. Such a genetic structure produces exceptionally high levels
      of heterozygosity and thus provides a tool for the individualization of tissue
      samples. Additionally, as the alleles are inherited in a Mendelian fashion, the
      minisatellites provide a superb tool for the identification of paternity (or
      maternity). Unlike standard blood groups, levels of variability are so high in
      populations studied to data that parentage can be established by inclusion rather
      than exclution. Homologous sequences are shown to exist in a variety of Old World
      primates. Visualization of genetic fingerprints in nonhumans may allow for
      determination of paternity where the pool of potential sires is available, while
      also providing information on levels of genetic variability. These capabilities
      will ultimately provide for better management of primate colonies. Used in
      concert with behavioral data, a number of sociobiological will also become more
      amenable to investigation.

PMID- 28514070
TI  - Predicting smallpox epidemics: A statistical analysis of two Finnish populations.
AB  - We analysis data on death due to smallpox in two subdivided Finish populations,
      the relatively isolated Aland Islands and the mainland parish of Kitee. The data
      span a 135-year time period (1750-1885). Logisitic regression and Cox
      proportional hazards models are used to assess the effects of predictive
      variables on (1) the probability that an individual subdivision experiences an
      epidemic and (2) the length of the time period between two epidemics in each
      subdivision. The predictive variables include population sizes, migration rates,
      geographic distance, and presence or absence of vaccination. Vaccination was
      found to be the single most important predicative variable (odds ratio = 6.3 in
      Aland and 4.4 in Kitee). No other variable were significant predicators in Kitee,
      while geographic distance was an additional significant predicator in Aland (odds
      ratio = 1.05). As expected, vaccination and geographic distance were both
      negatively associated with the probability of epidemic occurrence. The Mantel
      regression approach was used to evaluate the effects of independent variables on
      the probability that any two subdivisions experienced the same epidemic. Between
      subdivision migration rates were the most important predictive variable here, and
      population size was an important predictor in Aland but not in Kitee. The
      differing results in these two populations are explained in terms of differences
      in ecological setting and social organization.

PMID- 28514071
TI  - Molecular micro- and macroevolution in the primate alpha-globin gene family.
AB  - Because hemoglobin is among the most abundant and accessible proteins in the
      human body, the molecular basis for its production is arguably the best-known
      genetic system in any higher organism. The hemoglobin molecule is tetrameric and
      consists all developmental stage of two copies of each of two components, alpha
      like (141 amino acids) and beta-like (146 amino acids). The beta-like globins are
      located in a tight cluster on chromosome 11 and the alpha-like globins on
      chromosome 16. The alpha-globin cluster consists of several functional genes and
      nonfunctional pseudogenes, each the product of an ancient duplication of
      primordial genes. The cluster therefore affords us a window on the major features
      of molecular evolution. Within human populations hypervariable regions exist
      which may serve as useful genetic markers; and unequal crossing-over creates the
      most prevalent genotypes of alpha-thalassemia. Recently a new member of the alpha
      globin cluster was discovered in the orangutan genome and then subsequently in
      other taxa, including Homo sapiens. It appears to encode a unique alpha-like
      globin, and its protein product has yet to be isolated.

PMID- 28514072
TI  - Sibling correlations for skeletal age assessments by the Fels method.
AB  - Sibling correlations are reported for Fels skeletal ages from 2,622 mixed
      longitudinal hand-wrist radiographs of 285 boys and 276 girls. Because the
      observed correlations were irregular across age, they were smoothed by using
      kernel regression. The brother-sister correlations were generally lower than
      those for the other types of silbling pairs, but they were similar to the brother
      brother correlations after 11 years. The sister-sister correlations were
      considerably higher than the brother-brother and brother-sister correlations
      after 12 years. The present data do not provide clear evidence of involvement of
      the X chromosome in the timing of skeletal maturation, but after 12 years the
      present data suggest such an involvement.

PMID- 28514073
TI  - Application of molecular techniques to the study of human physiological
      variation.
AB  - Physiological differences between human populatios, manifest as apparent
      adaptation to extreme environments, as differences in patterna of growth and
      development, and as differences in prevalence of common disease, are a mofer
      subject area of human biology. The approach of the geneticist interested in
      understanding these difference has been largely that of the proverbial drunk
      looking for has lost keys. We have characterized those genes whose products are
      easily assayed from peripheral blood and sought post hoc statistical evidence for
      a relationship between gene frequencies and physiological variables. With few
      exceptions, this approach has failed to provide convincing evidence of the role
      of genes in determining physiological differences between populations. This is
      not unexpected since the genes which our knowledge of physiology would predict to
      be important in determining physiological homeostasis. Recent advances in
      molecular biology (particularly in the ability to isolate and clone specific
      genes and to use these as probes to detect genomic variation-polymorphism
      associated with these genes in human populations) and advances in our ability to
      resolve and visualize genetic variation in protein products provide the tools for
      a direct evaluation of the role of specific gene in determining physiological
      differences between populations. I will review the "candidate genes" available
      for the study of several physiological systems and present preliminary data from
      my laboratory related to genetic determinants of lipid metabolism.

PMID- 28514074
TI  - Association of adipose tissue distribution with relative skeletal age in boys:
      The Fels longitudinal study.
AB  - The association between relative skeletal age and fat patterning was analyzed by
      using data from the Fels Longitudinal Study for boys at chronological ages 8 to
      17 years. Fat patterning, as indicated by age-specific means for three skinfold
      thickness indices adjusted for weight/stature2 , was peripheral between 8 and 12
      years of chronological age but began to increase in a centripetal direction
      towards a generalized distribution after 13 years. From 14 to 17 years of
      chronological age, boys with advanced relative skeletal ages had more centripetal
      fat patterns, as indicated by the ratio subscapular/(subscapular + triceps)
      skinfolds, than did those with retarded skeletal ages. The mean annual increment
      in this ratio was significantly greater from 13 to 14 years of chronological age
      in boys with advanced relative skeletal ages than in those with retarded relative
      skeletal ages. Fat pattern index scores at 17 years of chronological age,
      however, could not be predicted from relative skeletal ages at 7, 11, or 14 years
      after adjustment for baseline fat pattern index scores and weight/stature2 . It
      was concluded that fat patterning, as quantified by the ratio indices used in
      this study, was associated more strongly with other indicators of relative
      maturity such as secondary sex characteristics in adolescent boys.

PMID- 28514075
TI  - Comparison of different bioelectrical impedance analyzers in the prediction of
      body composition.
AB  - To investigate the influence of different bioelectrical impedance (BI) analyzers
      on the prediction of body composition from bioelectrical resistive impedance (R),
      146 healthy white adults (73 men; 73 women) were studied at two independent
      laboratories: The University of Florida (UF) and the USDA, San Francisco. Whole
      body R was measured on each subject with three different BI analyzers. AT UF
      analyzers were: Valhalla Scientific model 1990-A (VH), RJL Systems model BIA-101
      (RJL), and Medi-Fitness model 1000 (MF). At USDA analyzers were: VH, RJL, and
      Bioelectrical Sciences model 200Z (BES). The largest difference in R (36 ohms, P
      ? 0.01) was noted between BES and VH at USDA. When applied to current BI
      prediction equations, the observed differences among analyzers resulted in
      differences in predicated % fat of up to 6.3% although most comparisons among
      mean values (79%) showed differences below 3%. Crossvalidation of the selected BI
      prediction equations with hydrostatistically determines body composition using
      the different R values revealed total errors of prediction (E) ranging from 3.6
      to 9.8% fat. The prediction equations were most accurate when used with data
      collected on the same instrument that was to used to develop the equation (E =
      3.6 to 5.3% fat). These findings indicate that different analyzers can be a
      significant source of variation when predicting body composition from R. To
      minimize this source of variation, it is recommended that BI prediction equations
      be used with the same type of instrument as that with which they were developed.

PMID- 28514076
TI  - Cellular and molecular mechanisms of neuronal degeneration: Amyotrophic lateral
      sclerosis, parkinsonism-demantia, and Alzheimer disease.
AB  - Hyperendemic Pacific foci of amyotrophic lateral sclerosis (ALS) and parkinsonism
      dementia (PD) represent naturally occurring models of late-onset chronic
      degenerative diseases that occur in different cultures, in different ecological
      zones, and among genetically divergent populations. These diseases occur among
      the Chamorros of the Mariana Islands, among the Auyu and Jakai of southern West
      New Guinea, and among the Japanese from the Kill Peninsula of Honshu Island.
      Accumulating evidence supports the hypothesis that a defect in mineral metabolism
      may be etiologically involved. Toxic and essential elements, such as calcium
      aluminum, and silicon cross the blood-brain barrier, deposit in affected neurons,
      and disrupt the axonal transport system, resulting in the abnormal
      copolymerization of cytoskeletal and amyloid beta-proteins in neurons. The
      pathological accumulation of these and other proteins into neurofibrillary
      tangles (the hallmark neuropathological lesion) causes neuronal dysfunction and
      death. Recent immunocytochemical and biochemical studies indicate that the
      amyloid beta-protein in Guamanian PD has an identical amino acid sequence, a
      similar N-terminus heterogeneity (variation in polypeptide length), and a similar
      immunoreactivity to those found in Alzheimer disease, suggesting a common
      mechanism of pathogenesis. Investigations are now underway to determine whether
      the abnormal accumulation of amyloid beta-protein in neurons of Guamanian
      patients with ALS and PD is the result of an aberrant post-translational
      modification of a larger precursor protein, an additional copy of the amyloid
      gene, or an impairment of amyloid catabolism all of which may be mediated by
      metal-enzyme or metal-gene interactions. The abnormal copolymerization of other
      proteins such as neurofilament, microtubule-associated protein tau, and ubiquitin
      in affected neurons suggests their interrelationship in the disease process.

PMID- 28514077
TI  - Secular trends in physique and physical fitness in Japanese students during the
      last 20 years.
AB  - The secular trend of increase in physical size of children has often been
      reported. Children today are bigger than before, but there is a question whether
      their physical fitness has improved as well. Methodological differences make it
      difficult to compare older and newer data. Data are presented from the tests and
      measurements of physical fitness of collage students measured once a year from
      1964 to 1987. Identical methods of measurement were used throughout. Sample sizes
      are of about 500-2,300 for each year, and year to year changes are discussed.
      Height, weight and chest grith measurements increased from 1964 to 1987 by 4.4
      cm, 5.3 kg, and 3.7 cm, respectively, and their regression coefficients for the
      years are .15, .24, and .15, respectively. The rate of increase of height is
      greater in the first half of these years. Vital capacity, standing broad jump,
      and 100 m dash records improved, but both right and left grip strength decreased.
      Back strength, ball throwing, and push-up performance did not change
      significantly. The results show that the size of young adults has increased, but
      that their physical fitness does not always follow a similar course.

PMID- 28514078
TI  - The silent zone of the lung in asthma under scrutiny again.

PMID- 28514079
TI  - Bioinspired Total Synthesis of Homodimericin A.
AB  - Homodimericin A is a remarkable fungal metabolite. This highly oxygenated racemic
      unsaturated polyketide poses a significant synthetic challenge owing to its
      sterically demanding central cagelike core containing eight contiguous
      stereogenic centers (including three quaternary stereocenters) and several
      carbonyl functionalities. On the basis of its proposed biogenetic synthesis, we
      designed a total synthesis of homodimericin A that proceeds in seven steps and
      features a double Michael reaction, an intramolecular Diels-Alder reaction, and
      an ene reaction.

PMID- 28514080
TI  - Methane emission from feather moss stands.
AB  - Data from remote sensing and Eddy towers indicate that forests are not always net
      sinks for atmospheric CH4 . However, studies describing specific sources within
      forests and functional analysis of microorganisms on sites with CH4 turnover are
      scarce. Feather moss stands were considered to be net sinks for carbon dioxide,
      but received little attention to their role in CH4 cycling. Therefore, we
      investigated methanogenic rates and pathways together with the methanogenic
      microbial community composition in feather moss stands from temperate and boreal
      forests. Potential rates of CH4 emission from intact moss stands (n = 60) under
      aerobic conditions ranged between 19 and 133 pmol CH4 h-1 gdw-1 . Temperature and
      water content positively influenced CH4 emission. Methanogenic potentials
      determined under N2 atmosphere in darkness ranged between 22 and 157 pmol CH4 h-1
      gdw-1 . Methane production was strongly inhibited by bromoethane sulfonate or
      chloroform, showing that CH4 was of microbial origin. The moss samples tested
      contained fluorescent microbial cells and between 104 and 105 copies per gram dry
      weight moss of the mcrA gene coding for a subunit of the methyl CoM reductase.
      Archaeal 16S rRNA and mcrA gene sequences in the moss stands were characteristic
      for the archaeal families Methanobacteriaceae and Methanosarcinaceae. The
      potential methanogenic rates were similar in incubations with and without methyl
      fluoride, indicating that the CH4 was produced by the hydrogenotrophic rather
      than aceticlastic pathway. Consistently, the CH4 produced was depleted in 13 C in
      comparison with the moss biomass carbon and acetate accumulated to rather high
      concentrations (3-62 mM). The delta13 C of acetate was similar to that of the
      moss biomass, indicating acetate production by fermentation. Our study showed
      that the feather moss stands contained active methanogenic microbial communities
      producing CH4 by hydrogenotrophic methanogenesis and causing net emission of CH4
      under ambient conditions, albeit at low rates.

PMID- 28514083
TI  - Pustulobullous variant of SDRIFE (symmetrical drug-related intertriginous and
      flexural exanthema).

PMID- 28514084
TI  - The education of one spouse and the fatness of the other spouse.
AB  - As shown in 702 wives with 9-12 years of education and 612 husbands similarly
      educated, the summed skinfolds of one spouse are influenced by the educational
      level of the other spouse, considerably so for the husbands. Women with 9-12
      years of education married to men of lower educational attainment are higher in
      the sum of four skinfolds while women of similar years of schooling married to
      men of college education and beyond are leaner (P=0.001). Possible explanations
      for the effect of the education of one spouse on the fatness level of the other
      spouse include selective mating in the direction set by the husband's
      socioeconomic milieu and fatness "drift" on the part of the wives, again in the
      direction of the husband's socioeconomic status (SES). While these findings do
      not lend themselves to a simple biological explanation, they do reiterate the
      effects of socioeconomic variables on fatness level within populations and even
      within families.

PMID- 28514082
TI  - Universal label-free in-process quantification of influenza virus-like particles.
AB  - Virus-like particles (VLPs) are becoming established as vaccines, in particular
      for influenza pandemics, increasing the interest in the development of VLPs
      manufacturing bioprocess. However, for complex VLPs, the analytical tools used
      for quantification are not yet able to keep up with the bioprocess progress.
      Currently, quantification for Influenza relies on traditional methods:
      hemagglutination assay or Single Radial Immunodiffusion. These analytical
      technologies are time-consuming, cumbersome, and not supportive of efficient
      downstream process development and monitoring. Hereby we report a label-free tool
      that uses Biolayer interferometry (BLI) technology applied on an Octet platform
      to quantify Influenza VLPs at all stages of bioprocess. Human (alpha2,6-linked
      sialic acid) and avian (alpha2,3-linked sialic acid) biotinylated receptors
      associated with streptavidin biosensors were used, to quantify hemagglutinin
      content in several mono- and multivalent Influenza VLPs. The applied method was
      able to quantify hemagglutinin from crude samples up to final bioprocessing VLP
      product. BLI technology confirmed its value as a high throughput analytical tool
      with high sensitivity and improved detection limits compared to traditional
      methods. This simple and fast method allowed for real-time results, which are
      crucial for in-line monitoring of downstream processing, improving process
      development, control and optimization.

PMID- 28514085
TI  - Is poor early growth related to adult immune aging? A follow-up study.

PMID- 28514081
TI  - Weight loss and improved metabolic outcomes amongst rural African American women
      in the Deep South: six-month outcomes from a community-based randomized trial.
AB  - BACKGROUND: Obesity is highly prevalent in African American women, especially
      those in the rural southern USA, resulting in persistent health disparities.
      OBJECTIVE: To test the effectiveness of an evidence-based behavioural weight loss
      intervention delivered by community health advisors to African American women in
      the rural south. DESIGN AND METHODS: Overweight or obese African American women
      (30-70 years) from eight counties in Mississippi and Alabama participated in a 24
      month randomized controlled trial of an evidence-based behavioural weight loss
      programme augmented with community strategies to support healthy lifestyles
      (Weight Loss Plus, N = 154) compared to the weight loss programme alone (Weight
      Loss Only, N = 255). This study reports on 6-month outcomes on primary (weight
      change) and secondary (waist circumference, blood pressure, lipids, fasting blood
      glucose) outcomes, coinciding with the completion of the intensive weight loss
      phase. RESULTS: Weight Loss Only participants lost an average of 2.2 kg (P <
      0.001). Weight Loss Plus participants lost an average of 3.2 kg (P < 0.001). The
      proportion of the total sample that lost at least 5% of their body weight was
      27.1% with no difference between treatment groups. Similarly, we observed
      statistically significant reductions in blood pressure, waist circumference and
      triglycerides in each treatment group, with no statistical differences between
      groups. CONCLUSION: Trained lay health staff and volunteers from the rural
      southern USA were able to deliver a translation of a high-intensity behavioural
      intervention targeted to African American women, resulting in clinically
      meaningful weight loss and improvement in other metabolic outcomes in a
      significant proportion of participants.

PMID- 28514086
TI  - Selective migration as a bias in modernization studies: Premigration differences
      in morphology and blood pressure among 15-30 year-old American Samoans.
AB  - Premigration differences in anthorpometry and blood pressure are examined for
      evidence of selective migration for biological characteristics. We conducted a 5
      years follows-up of the migration status of 99 American Samoans 15-30 years old
      who had been previously examined in 1981 and found that 33 had migrated. Analysis
      of covariance of the baseline anthorpometry and blood pressures of the
      nonmigrants (n = 58) and those who subsequently migrated (n = 29) indicates that
      selective migration does occur among young American Samoan adults. Migrants of
      both sexes tended to be younger and leaner and had significantly lower mean blood
      pressures than nonmigrants even before migration. Selective migration of lean
      individuals with lower blood pressures may contribute to the lower blood
      pressures of migrants from American Samoa living in Hawaii or to the
      heterogeneity in other Samoan populations. These results are one of the few
      examples of biological selectivity demonstrated to date and illustrate the
      dangers of assuming that the effects of selective migration are negligible in
      studies of migration and health.

PMID- 28514087
TI  - Amyotrophic lateral sclerosis and parkinsonism-dementia of Gaum: Clinical,
      epidemiological, and genetic patterns.
AB  - The strikingly high incidence of amyotrophic lateral sclerosis (ALS) and
      parkinsonism-dementia (PD), two uniformly fatal neurodegenerative disorders which
      often occur in the same families and occasionally in the same individual, was
      recognized on Guam more than three decades ago. Since the first systematic
      observations began, nearly 800 Guamanian Chamorro patients have been clinically
      diagnosed as having either disease. The original incidence rates for ALS and PD
      accounted for one in five deaths among Chamorros over ago 25. During the past 30
      years, however, the incidence and mortality rates have dramatically declined and
      today the risk to Guamanian chamorros is only several-fold higher than that for
      non-Chamorro residents of the continental United States. The accumulating
      epidemiological and genetic data strongly suggest that environmental factors are
      primarily involved in the etiology and pathogenesis of these disorders. The high
      incidence focus of ALS and PD on Guam and similar, but less well-studied, foci in
      West New Guinea and the Kii Peninsula of Japan represent natural paradigms of
      chronic degenerative disease that have provided new information and insights for
      understanding not only ALS and PD, but other neurological disorders such as
      classical ALS, Parkinson disease, Alzheimer disease, and early neuronal aging,
      insights that might otherwise not have been forthcoming from studies of low
      incidence sporadic disease in large cosmopolitan Western communities.

PMID- 28514088
TI  - Dietary patterns of older adults in the United States, NHANES II 1976-1980.
AB  - The second National Health and Nutrition Examination Survey (NHANES II) 1976-1980
      provided detailed information concerning the dietary patterns of older Americans.
      By using 24-hour dietary recall and food frequency questionnaires, the dietary
      patterns of 2,615 adults aged 65-74 years were evaluated by types of living
      arrangements (living alone, with a spouse, or with someone other than a spouse)
      and income level (below poverty, at or above poverty). Analyzed indicators of
      dietary quality were caloric and nutrient intake, food group intake and
      frequency, and number of meals skipped. The most favorable dietary patterns of
      elderly persons were associated with living with a spouse, especially for men.
      Low-income men not living with a spouse were at highest risk of dietary
      inadequacy. For women, income was more strongly associated with dietary patterns
      than type of living arrangement. Results from NHANES II compare favorably to
      those of the first National Health and Nutrition Examination Survey (NHANES I)
      1971-1974.

PMID- 28514089
TI  - Linear statistical model for growth in stature from birth to maturity.
AB  - A model for the physical growth of individual children from birth to adulthood is
      proposed which is linear in the model parameters. The advantages of linear over
      nonlinear models include the relative ease and costs of fitting the model to data
      of individuals and the fact that statistical methods are more readily available
      for analysis of parameters from linear models than for nonlinear models. The
      proposed linear model and the non-linear triple logistic model are both fit to
      the measured lengths of two boys and two girl followed from birth to 18 years of
      age.

PMID- 28514090
TI  - Population biology and aging: The example of blood pressure.
AB  - Cross-sectional studies of aging trends in traditional societies are open to
      question because of widespread cohort trends, which can have different impacts on
      different age groups. An illustration of this problem is taken from blood
      pressures studies on the classic Framingham Heart Study, in which cross-sectional
      results give a very different indication from longitudinal results of aging
      trends in this modern population. Semilongitudinal studies of blood pressure in
      Soloman Islands populations are reviewed to show the dramatic indicators in
      modernising groups there of rapid blood pressure increases over approximately a
      decade in adult cohorts of all ages. The partitioning of aging vs. cohort effects
      is only possible with this technique.

PMID- 28514091
TI  - Who gave whom hemoglobin S: The use of restriction site haplotype variation for
      the interpretation of the evolution of the betaS -globin gene.
AB  - The hypothesis that three separate mutations to the betaS -globin gene have
      occurred in Africa in challenged. The distributions of the betaS and other beta
      globin haplotypes and a simulation of the diffusion of the betaS gene are
      presented and argued to be more in accord with the rapid diffusion of a single
      mutant that by recombination and gene conversion now occurs on several different
      haplotypes.

PMID- 28514092
TI  - Are the known chronic diseases related to the human lifespan and its evolution?
AB  - There is running debate in the gerontological research literature concerning the
      relationship between causes of mortality and the human lifespan. Much of this
      debate concerns whether we can, by biomedical intervention in known degenerative
      diseases, square the human survivorship curve, at a point near some human
      "maximum lifespan potential" (MLP) This paper examines the concepts of lifespan
      and MLP and the relationship between the shape of the survivorship curve and the
      pattern of age-specific mortality from chronic disease. The MLP need only be
      viewed as a statistical phenomenon whose genetic determination relates to general
      human metabolism rather than to programmed events occurring at the end of the
      human lifespan. The available evidence suggests that slowing of underlying
      senescence processes will not have the desired effects on survivorship, but
      rather the opposite.

PMID- 28514093
TI  - Development of protocols for the application of salivary steroid analysis to
      field conditions.
AB  - The simple and noninvasive nature of sample collection for salivary steroid assay
      makes this technique well suited for anthropological field studies of human
      reproduction function. In this study, a series of controlled experiments was done
      to investigate the effects of modifying common clinical sample collection and
      storage procedures for field use. Matched sets of samples were assayed for four
      steroids to test the effects of using plastic, rather than glass, collection
      tubes, of using a stimulant to aid collection, and of storing samples at ambient
      temperature rather than frozen. Our work confirms the feasibility of collecting
      samples for salivary steroid assay in field situations, while at the same time
      emphasizing the importance of considering methodological issues in planning and
      interpreting such studies. Our results show that it is acceptable to use
      polystyrene collection tubes and a carefully chosen stimulant to aid collection,
      and that samples can be stored at ambient temperature in the field when frozen
      storage is not available. In addition, they demonstrate the necessity for
      consistency in sample collection and storage procedures.

PMID- 28514094
TI  - Cause-specific mortality, life expectancy, and debilitation in aging polynesians.
AB  - Between 1950 and 1980 life expectancy among middle-aged American Samoan men
      increased 22%; among women it increased 36%. The largest proportional increase
      were observed after age 65% Men 29%, women 118%. This study examined whether
      increasing longevity health of older Samoans. Cause-specific mortality data were
      used to calculate multiple decrement life tables for American Samoa by decades
      for both sexes from 1950 to 1979. Changes in two life table parameters were
      examined: The probability of dying from, and the remaining life expectancy among
      persons who would eventually die from, pneumonia/influenza, infections, cancer,
      or cardiovascular disease (CVD) after birth and after age 45. Pneumonia and
      infections may indicate frailty or delibitration in older individuals. The
      probability of dying from a specific cause after a particular age reflects its
      relative importance for survivors to that age. Residual life expectancy indicates
      whether older individuals are succumbing at earlier ages or surviving longer the
      risks of death from specific causes. Trends in the probability of dying from, and
      life expectancy among those ultimately dying from, pneumonia and infections did
      not suggest improved survival of debilitated individuals. Rather, they indicated
      that older Samoans may have had greater average resistance to pneumonia and
      infections in later cohorts. How much this was related to improved medical care
      and availability was not clear from the available data. However, Samoans who died
      from CVD and cancer did not survive longer than their counterparts had in earlier
      decades. Thus, there was little opportunity for an increase in debilitation among
      aging Samoans due to the longer-term survival of the chronically ill.

PMID- 28514095
TI  - Relation of community size to endogamy in a traditional soceity: Patzcuaro,
      Mexico, 1903-1932.
AB  - Community endogamy is often a preferred cultural practice, although in
      traditional populations small community size make universal endogamy difficult
      for lack of appropriate mates. Using civil marriage records from an early 20th
      century Tarascan Mexican population, the association of local community size,
      transferred to long values, and endogamy is tested using 2,663 marriages for 40
      locations situated in two municipios (counties) forming the Southwest rim of lake
      Patzcuaro. The association is linear, with a correlation coefficient of 0.62 for
      completely endogamous marriages and 0.55 for individual endogamy. If the two
      municipio cabeceras (county seats) are removed, the r values improve to 0.83 and
      0.80 (all at P < 0.001), respectively. Community size is thus important, but in a
      complex settlement area central place locations, such as the cabeceras, also
      exert a strong disruptive influence on the simple pattern.

PMID- 28514096
TI  - Evolutionary, biosocial, and cross-cultural perspectives on the variability in
      human biological aging.
AB  - Because of our traditional emphasis on evolutionary processes and the causes of
      variability, human biologists have contributed to the understanding of
      variability in human biological aging. The shared interests of human
      characterized by increased phenotypic variation in later stages of life and by
      reduced adaptive capacity. The papers in this issue illustrate the unique blend
      of evolutionary, biosocial, and cross-cultural perspectives used by human
      biologists to study the variation in biological aging. The papers present
      examples of common methodological paradigms such as theoretical/mathematical
      models, epidemiological studies, natural experiments, and studies of isolated
      foci of diseases. The principles of human adaptability and the premises of the
      life-course perspective may provide the foundation for a conceptual framework
      that integrates the study of biological, behavioral, and social aspects of human
      aging. Human biologists can play an important role in refining the theoretical
      and methodological tools that will be needed to understand the variability in
      human aging in populations throughout the world.

PMID- 28514098
TI  - Food restriction research: Its significance for human aging.
AB  - The total lack of knowledge concerning the nature of the primary aging processes
      coupled to the lack of biomarkers of aging has made it difficult to devise
      fruitful approaches for the study of aging. Indeed, the only index of aging about
      which there is general agreement is the life span of the species (i.e., the
      maximum age attained by members of the species). Only one manipulation has been
      found which extends the life span of a mammalian species and that is food
      restriction in rodents. In addition to increasing life span, food restriction
      also retards almost all age-associated physiological changes and diseases
      processes. It is concluded that food restriction has these diverse actions
      because it retards the primary aging processes. Recent research has been focused
      on the mechanisms by which food restriction influences the primary aging
      processes because it is believed that such knowledge will provide insight on the
      basis nature of aging. Available evidence pints to the neural an endocrine system
      as couplers of food restriction to the aging processes. Of particular current
      interest are the effects of food restriction on protein turnover and free radical
      metabolism. The importance of food restriction to human aging relates to the
      information it is expected to yield on the nature of the primary aging processes
      in all mammalian species and the database it should provide for interventions of
      human aging.

PMID- 28514097
TI  - Relationship between body composition and the components of somatotype.
AB  - In a sample of 422 adults (200 females and 222 males) aged 18-73 years, the
      relationship was determined between somatotype estimated by the Health-Carter
      (Am. J. Phys. Anthropol. 27:57-74, 1967) method and body composition variables
      determined by using hydrodensitometry (HD) and Bioelectrical Impedance Analysis
      (BIA). The anthropometric (ANC) dimensions used to estimate somatotype were
      positively correlated with the endomorphic and mesmorphic components and
      negatively correlated with the ectomorphic component. For the BIA measurements,
      resistance (R) was negatively correlated with the mesomorphic component; and
      reactance (XC) was negatively correlated with the endomorphic component; both
      measurements were positively correlated with the ectomorphic component. The HD
      negative correlations were observed between mass in water and the endomorphic and
      mesomorphic components, and positive correlations were observed with the
      ectomorphic component. Body volume and surface area were positively correlated
      with the endomorphic and mesomorphic components and negatively correlated with
      the ectomorphic component. Percent fat and fat weight were related to each of the
      three components of somatotype for males and females. Fat-free weight for males
      was also related to the mesomorphic and the ectomorphic components.

PMID- 28514099
TI  - Monthy growth increments from a longitudinal study of Canadian infants.
AB  - Reference data for 1 month increments in weight, recumbent length, and head
      circumference, at ages 1 to 12 months, have been derived from serial data for 351
      full-term Canadian infants. This derivation was achieved by (1) fitting a family
      of three parameter mathematical models to the data for each infant, (2) using
      these models to estimate values 1 month apart (3) calculating 1 month increments
      from the status values of 1 month intervals, (4) obtaining the distributions of
      these increments, and (5) presenting the percentiles of these increments in
      tables and in figures. The 1 month increments decreased with age during infancy
      in each sex, and these increments tended to be more rapid for boys than for
      girls. It is suggested that these reference data are suitable for the assessment
      of growth rates in infants born at term in Canada or in the United States. They
      can be used to assist the early identification of deviations from expected growth
      rates for individuals and to compare population samples.

PMID- 28514101
TI  - Rearrangement of a P4 Butterfly Complex-The Formation of a Homoleptic Phosphorus
      Iron Sandwich Complex.
AB  - The versatile coordination behavior of the P4 butterfly complex [{Cp'''Fe(CO)2 }2
      (MU,eta1:1 -P4 )] (1, Cp'''=eta5 -C5 H2t Bu3 ) towards different iron(II)
      compounds is presented. The reaction of 1 with [FeBr2 ?dme] (dme=dimethoxyethane)
      leads to the chelate complex [{Cp'''Fe(CO)2 }2 (MU3 ,eta1:1:2 -P4 ){FeBr2 }] (2),
      whereas, in the reaction with [Fe(CH3 CN)6 ][PF6 ]2 , an unprecedented
      rearrangement of the P4 butterfly structural motif leads to the cyclo-P4 moiety
      in {(Cp'''Fe(CO)2 )2 (MU3 ,eta1:1:4 -P4 )}2 Fe][PF6 ]2 (3). Complex 3 represents
      the first fully characterized "carbon-free" sandwich complex containing cyclo-P4
      R2 ligands in a homoleptic-like iron-phosphorus-containing molecule.
      Alternatively, 2 can be transformed into 3 by halogen abstraction and subsequent
      coordination of 1. The additional isolated side products, [{Cp'''Fe(CO)2 }2 (MU3
      ,eta1:1:2 -P4 ){Cp'''Fe(CO)}][PF6 ] (4) and [{Cp'''Fe(CO)2 }2 (MU3 ,eta1:1:4 -P4
      ){Cp'''Fe}][PF6 ] (5), give insight into the stepwise activation of the P4
      butterfly moiety in 1.

PMID- 28514100
TI  - MicroRNA-128 promotes apoptosis in lung cancer by directly targeting NIMA-related
      kinase 2.
AB  - BACKGROUND: MicroRNA-128 (miR-128) serves as a regulator by inducing cancer cell
      apoptosis, differentiation, the epithelial-to-mesenchymal transition process, and
      tumor growth by mediating different targets. NIMA-related kinase 2 (NEK2) is
      aberrantly expressed in lung cancer. The miR-128/NEK2 pathway has been reported
      to predict prognosis in colorectal cancer; however, the determination of a
      relationship between miR-128 and NEK2 in lung cancer has remained elusive. We
      explored the association between miR-128 and NEK2 in lung cancer. METHODS: MiR
      128 and NEK2 expression were examined in 15 lung cancer tissues by real time-PCR.
      Lung cancer SK-MES-1 cells were transfected with miR-128 mimic, an inhibitor or a
      negative control. MiR-128 and NEK2 expression levels were detected using
      quantitative real time-PCR and Western blot. SK-MES-1 cell apoptosis was
      performed by flow cytometry. RESULTS: Compared to adjacent non-tumor tissues, miR
      128 was downregulated and NEK2 was upregulated in 15 lung cancer tissues. Lung
      cancer SK-MES-1 cells transfected with miR-128 mimic induced a higher apoptotic
      rate than those transfected with the negative control. Dual luciferase assay
      further confirmed that NEK2 was a direct target of miR-128 in lung cancer, and
      transfection with miR-128 mimic could decrease the NEK2 protein level while the
      miR-128 inhibitor increased NEK2 expression. Finally, the apoptotic effect of
      lung cancer cells induced by miR-128 mimic could be reversed by NEK2
      overexpression. CONCLUSIONS: NEK2 was regulated by miR-128 in lung cancer and miR
      128 induced lung cancer cell apoptosis by mediating NEK2 expression.

PMID- 28514102
TI  - Cutaneous squamous cell carcinoma treated with preoperative intraarterial
      chemoradiation therapy.

PMID- 28514103
TI  - Relative utility of carpal skeletal ages.
AB  - The need to assess the carpal bones when a skeletal age is being obtained for a
      handwrist radiograph has been determined. The mixed longitudinal data that were
      analyzed had been obtained from 335 boys and 322 girls at 1, 4, 7, 10, 13, and 16
      years of age. The FELS assessment method, which was used to obtain the skeletal
      ages, provides the standard error of each assessment; each of these standard
      errors is determined by the amount of relevant information available from a
      radiograph. Utilizing the standard errors for paired assessments made with and
      without the inclusion of the carpal bones, it was concluded that the carpal bones
      should be assessed from 7 to 13 years in boys and from 4 to 10 years in girls,
      but they need not be assessed before or after these age ranges.

PMID- 28514104
TI  - Measurement of short-term growth with a new knee height measuring device.
AB  - Information on short-term growth (growth over periods of 1 month or less) has
      potential use in the clinic for treatment of children with growth disorders, and
      knowledge about patterns of short-term growth may also contribute to an
      understanding of growth control mechanisms. Limitations of measurement
      reliability for most measurements of linear growth have generally confined us to
      evaluation of growth over periods 3 month or longer. This report introduces the
      Knee Height Measuring Device (KHMD) The Knee Height Measuring Device is available
      from Intersciences Development Associates, 3508 Market St., Philadelphia, PA
      19104 (215-662-0700), patent pending. , which can measure changes in size of the
      lower leg of approximately 0.5 mm and thus assist in evaluation of short-term
      growth. It is smaller, more portable, and less expensive than the Valk lower leg
      measuring device (knemometer) and uses a less subjectively biased measurement
      technique. Preliminary comparisons using a sample of 15 children measured twice
      at a 28-day interval of the validity and reliability of a prototype KHMD and the
      Valk knemometer. Yielded an intraobserver error of 0.295 for the KHMD and 0.206
      for the knemometer. Agreement of the two instruments on the presence of
      detectable growth was 90%. Pearson correlation of growth rates detected by the
      two instruments was 0.73. After additional alterations improving the design and
      measurement methodology of the KHMD, 103 children 6-10 years old were measured at
      28-day intervals from January to June and then at 3-month intervals from June to
      December of 1988 using the improved KHMD alone. Intraobserver error for these
      measurements was 0.22 mm. This error was modestly associated with the weight of
      the child (r=.31) but unrelated to sex, height, or growth in any dimension.
      Interobserver error for 22 children measured by two observers was 0.33 mm. We
      analyzed the knee height growth data primarily to test whether monthly growth
      could be reliably detected by this instrument. Average 28-day knee height growth
      was 1.76+/-0.3 mm, which is three times greater than the 0.5 mm growth detectable
      with the KHMD. Over any given 1-month interval, fewer than 10% of the children
      had growth less than that which could be detected with the instrument. We
      conclude that the KHMD can reliably detect growth over a 1-month interval and has
      potential clinical use for monitoring growth and for evaluating the
      characteristics and associations of short-term growth.

PMID- 28514105
TI  - Changes in anthropometric indices of body composition with age in a healthy
      elderly population.
AB  - Changes in body composition are known to occur with old age, but there is limited
      knowledge of the normal values rates of change in anthropometric indices of body
      composition or the distribution of these changes in the elderly. In the present
      study, 98 elderly white men and 122 elderly white women were followed
      prospectively for 6 years. These participants were divided into 5-years cohorts
      on the basis of age at the start of the study in 1980. Separate linear
      regressions of triceps skinfold thickness, midarm circumference, midarm muscle
      area, and weight divided by stature squared on age were computed for each
      participant. The mean annual changes or slopes for these indices were small for
      each sex. A loss of subcutaneous adipose tissue was indicated with age, but the
      effects of compression or measurement error may hamper the detection of changes
      in indices of body composition in the elderly.

PMID- 28514106
TI  - Semai Senoi mortality: Two-census method.
AB  - The mortality pattern of a subpopulation of Semai Senoi of Malaysia is studied by
      using a two-census method. The method yields abridged life tables for both sexes
      as well as an estimate of the birth rate. The life tables show that Semai
      mortality is reduced compared to estimates based on stable population methods for
      the population prior to 1969. Increased health care availability seems to account
      for this lower mortality.

PMID- 28514107
TI  - Do reproductive patterns affect maternal nutritional status?: An analysis of
      maternal depletion in Lesotho.
AB  - Poor pregnancy outcomes in developing countries have often been blamed on
      maternal depletion or on the cumulative nutritional drain of many closely spaced
      pregnancies. Despite its widespread acceptance, the maternal depletion hypothesis
      remains unproven. This study examines nutritional status and fertility history
      for 873 women in highland Lesotho. Parity, age, pregnancy status, length of last
      closed birth interval, open interval, and median birth interval were used to
      predict nutritional status (BMI, triceps skinfold, arm muscle area). While there
      is evidence that both short-term and long-term nutritional depletion are related
      to lactation and pregnancy spacing, both BMI and triceps fat increase with
      parity. For this population, then, the assumption of cumulative depletion due
      simply to high fertility is not supported.

PMID- 28514108
TI  - Validity of anthropometric percent fat prediction equations for use with pregnant
      women.
AB  - The purpose of this investigation was to determine the validity of five different
      skinfold prediction equation for use in forecasting the percent body fat of
      pregnant women. Twenty-one pregnant women underwent hydrostatic and skinfold
      thickness determinations of percent body fat at 6-10, 16, and 28 weeks of
      gestation. The correlations between hydrostatic and anthropometric determinations
      of percent body fat were high during the three test periods (r= .78 to r = .89).
      The slopes of the line of best fit between the criterion (hydrostatic weighing)
      and predicted variable (prediction equation) decreased across pregnancy. The
      anthropometric prediction equations tended to overestimate percent body fat
      changes in comparison to the hydrostatically determined percent body fat changes.
      Skinfold thickness measurements can be used as a prepregnancy aid in determining
      recommended weight gain during pregnancy and as a measure of subcutaneous fat
      status during pregnancy. However, anthropometric prediction equations should not
      be used during the later stages of pregnancy to estimate percent fat or percent
      fat changes.

PMID- 28514109
TI  - The British, American NCHS, and Dutch weight standards compared using the LMS
      method.

PMID- 28514110
TI  - X-linked pattern of inheritance for serial measures of weight/stature2.
AB  - The pattern of family resemblance for long-term serial measures of
      weight/stature2 (W/S2 ) in approximately 500 individuals from the Fels
      Longitudinal Growth Study suggests that X-linked genes may be contributing to the
      variability in this trait among children, particularly during the prepubertal age
      range of 2-9 years. In this data set, W/S2 was measured serially at the same ages
      in all family members. Thus, a parent-child correlation at a specific age can be
      determined even though the measurements were made on the child a generation later
      than on the parent. The pattern of family resemblance at each annual age up to 10
      years and at ages 14-18 years is consistent with the presence of an X-linked
      genetic effect. Opposite-sex parent-child pairs are more similar than same-sex
      pairs, and sister-sister pairs are more similar than brother-brother or brother
      sister pairs at these ages. Furthermore, when the distribution of W/S2 is
      examined separately in boys and girls, there is evidence of commingling in the
      distribution of boys from 5 to 8 years of age but not in girls. This is
      consistent with the existence of a major X-linked gene with a frequency of about
      3%. This pattern of family resemblance and commingling suggestive of partial X
      linkage for W/S2 has not been detected previously because cross-sectional family
      studies generally compare individuals at different stages of growth.

PMID- 28514111
TI  - Body weight/height relationship: Exponential solution.
AB  - Regression of weight (W) on height (H) in all higher primates is of exponential
      form W = a . exp(H . b) and is uniform for both nongrowing adults and growing
      children. Parameter a values are always close to 2.0 and b to 0.02. The
      exponential equation fits ontogenetic data better than the traditional allometric
      power curve. The exponential nature of the W/H regression during growth may be
      explained by mechanisms of cell proliferation: Arithmetic growth of the skeleton
      at epiphyseal plates and geometric proliferation of many other tissues of the
      body. Sexual dimorphism and interpopulational differences in a and b values are
      interpretable: e.g., girls have lower initial weight (lower a values) than boys,
      and Africans (low b values) grow "slimmer" than Eskimos. The effects of improved
      environmental conditions can also be described. Children of the same ethnic group
      have higher a and lower b values when growing in better condition because of
      higher initial weights, but acquire elongated physiques during growth. Use of
      exponential W/H relationship as growth standards and for reconstruction of body
      build in fossil material is postulated.

PMID- 28514112
TI  - Neonatal nutrition and longitudinal growth in baboons: Adiposity measured by
      skinfold thickness.
AB  - This paper reports the results of a 5 year longitudinal experiment that (1)
      examined growth in adiposity of a group of 48 clinically normal olive savannah
      baboons (Papio cynocephalus anubis) who were randomly assigned at birth to one of
      three diet treatments that differed, during the first 16 weeks, in the amount of
      nutrients they provided; (2) tested the hypothesis that different amounts of food
      availability during the neonatal period (birth to 16 weeks) had a significant
      effect on growth and development of adiposity in the subsequent infant, juvenile,
      and adolescent periods; and (3) evaluated the extent to which underfed (LC) and
      overfed (HC) subjects were capable of growth canalization. Each diet contained
      different caloric densities but the same proportion of fat (34%), carbohydrate
      (55%), and protein (11%). All animals were fed the same volume of formula;
      however, HC subject were fed 40% more calories than MC subjects, who were fed 40%
      more calories than the LC subjects. Growth and development of adiposity were
      assessed by measuring neck, triceps, subscapular, and suprailiac skinfolds weekly
      from birth to 16 weeks and at 13 week intervals from 26 to 260 weeks of age. We
      found that during the first 16 weeks of the experiments, baboon growth was
      strongly influenced by food shortages but not by excesses; however, when the
      dietary treatment ceased, growth appeared to be strongly regulated by a genetic
      component (developmental canalization) and tended to return to a more normal
      growth pattern within a 26 week time frame. Males and females exhibited
      differences in adipose development in that males did not exhibit residual
      treatment effects while females tended to retain the effects of neonatal dietary
      treatments through early adolescence.

PMID- 28514113
TI  - Semai Senoi fertility and population dynamics: Two-census method.
AB  - The fertility and parameters of population growth of the Semai Senoi of Malaysia
      are studied by using a two-census method based on nonstable population theory.
      Semai fertility is shown to be moderately high; female completed fertility is
      7.42 children and the crude birth rate is greater than 0.050. Previous estimates
      of Semai mortality rates are also moderately high but are insufficient to balance
      birth; thus, the overall rate of growth is presently nearly 2%. Compared with an
      earlier description of the pre-1969 Semai population, fertility has increased
      markedly leading to a nearly threefold increase in the annual growth rate.

PMID- 28514114
TI  - Finding Relevant Parameters for the Thin-film Photovoltaic Cells Production
      Process with the Application of Data Mining Methods.
AB  - A data mining approach is proposed as a useful tool for the control parameters
      analysis of the 3-stage CIGSe photovoltaic cell production process, in order to
      find variables that are the most relevant for cell electric parameters and
      efficiency. The analysed data set consists of stage duration times, heater power
      values as well as temperatures for the element sources and the substrate - there
      are 14 variables per sample in total. The most relevant variables of the process
      have been found based on the so-called random forest analysis with the
      application of the Boruta algorithm. 118 CIGSe samples, prepared at Institut des
      Materiaux Jean Rouxel, were analysed. The results are close to experimental
      knowledge on the CIGSe cells production process. They bring new evidence to
      production parameters of new cells and further research.

PMID- 28514115
TI  - Rhodium-Catalyzed Regioselective Domino Azlactone-Alkyne Coupling/Aza-Cope
      Rearrangement: Facile Access to 2-Allyl-3-oxazolin-5-ones and Trisubstituted
      Pyridines.
AB  - Rhodium-catalyzed regioselective addition of azlactones to internal alkynes
      combined with aza-Cope rearrangement provides efficient atom economic access to 2
      allyl-3-oxazolin-5-one derivatives. Extension to a triple domino process, in
      which the above process is combined with in situ azlactone formation starting
      from amino acids renders this process even more attractive. Subsequent
      thermolysis of the 2-allyl-3-oxazolines enabled the de novo synthesis of
      trisubstituted pyridines.

PMID- 28514117
TI  - Tailored Ahp-cyclodepsipeptides as Potent Non-covalent Serine Protease
      Inhibitors.
AB  - The S1 serine protease family is one of the largest and most biologically
      important protease families. Despite their biomedical significance, generic
      approaches to generate potent, class-specific, bioactive non-covalent inhibitors
      for these enzymes are still limited. In this work, we demonstrate that Ahp
      cyclodepsipeptides represent a suitable scaffold for generating target-tailored
      inhibitors of serine proteases. For efficient synthetic access, we developed a
      practical mixed solid- and solution-phase synthesis that we validated through
      performing the first chemical synthesis of the two natural products Tasipeptin A
      and B. The suitability of the Ahp-cyclodepsipeptide scaffold for tailored
      inhibitor synthesis is showcased by the generation of the most potent human HTRA
      protease inhibitors to date. We anticipate that our approach may also be applied
      to other serine proteases, thus opening new avenues for a systematic discovery of
      serine protease inhibitors.

PMID- 28514118
TI  - Anaphylactic shock caused by intradermal testing with cefuroxime.

PMID- 28514116
TI  - Changes in main pulmonary artery diameter during follow-up have prognostic
      implications in pulmonary arterial hypertension.
AB  - BACKGROUND AND OBJECTIVE: A dilated pulmonary artery (PA) is a common finding in
      patients with pulmonary arterial hypertension (PAH). Little is known on the
      variations in PA size over time and whether these changes track with disease
      severity and/or predict long-term survival. METHODS: We included patients with
      PAH who had at least two computed tomography (CT) scans of the chest done on
      different visits. Both scans matched the use of i.v. contrast. RESULTS: Pairs of
      CT scans were compared in 113 PAH patients. During a median (interquartile range
      (IQR)) time difference between scans of 8 (IQR: 3.5-20.0) months, we noted an
      increase in main PA diameter of 0.5 +/- 1.8 mm (mean +/- SD) (P = 0.008). When CT
      scans were performed >12 months apart (n = 47), the main PA diameter increased or
      decreased by >1 mm in 40% and 13% of the patients, respectively. An increase in
      main PA diameter was associated with lower PA compliance, higher right
      ventricular (RV) systolic pressure, worse RV function and a decline in 6-min walk
      distance. During a median (IQR) follow-up of 33 (IQR: 4.5-47) months, 53 (46.9%)
      patients died. The change in PA diameter was a significant predictor of mortality
      (hazard ratio (HR) per mm increase: 1.33 (95% CI: 1.11-1.61), P = 0.002) when
      adjusted for difference in time and slice thickness between CT scans, age,
      gender, PAH aetiology and pulmonary vascular resistance. CONCLUSION: In PAH
      patients, an increase in CT-derived main PA diameter over time is associated with
      progression in pulmonary pressures, RV dysfunction, a decline in functional
      capacity and higher mortality.

PMID- 28514119
TI  - Soft, slightly tender perianal nodules.

PMID- 28514121
TI  - [SHIFT WORK AND ITS HEALTH HAZARDS].
AB  - INTRODUCTION: Work in repeated changing shifts, in general, and night-shifts, in
      particular, is considered a necessity, encompassing many professions, among them
      physicians and nurses. This type of work has been shown to adversely affect the
      normal function of the human body circadian rhythm. This negative influence in
      turn, is considered to increase characteristic types of morbidity such as
      metabolic syndrome, type 2 diabetes and increased rate of cardiovascular
      morbidity. Women working in night-shifts in particular, have been found to face
      increased rates of breast cancer, as well as menstrual disturbances and decreased
      fertility. Despite many physiologic explanations for the deleterious effects of
      changing or night-shifts on human's health, there is no clear notion for the
      prevention or treatment of these health hazards. In light of the necessity for
      such a mode of employment in our modern world, the issues of taking care of the
      affected workers should be considered on a national scale.

PMID- 28514122
TI  - [IS ANTI-THROMBOTIC PROPHYLAXIS WARRANTED IN FERTILITY AND IN-VITRO FERTILIZATION
      TREATMENTS?]
AB  - INTRODUCTION: Assisted reproductive technology (ART) treatments are potential
      risk factors for thromboembolism (TE) due to excessive estrogen levels. Recently,
      several studies have shed new light on this matter. AIMS: To review the
      literature to assess the risk for TE during ART and to establish guidelines
      regarding thrombophylaxis. METHODS: A search was conducted of PubMed, Medline,
      Cochrane and clinicaltrials.gov. The search terms were fertility, assisted
      reproductive technology, IVF, thromboembolism, thrombosis and anticoagulation.
      Case reports and reviews were excluded. RESULTS: Three cohort studies and one
      cross-sectional study were included; one examined the effect of ART on TE risk
      after cycles not resulting in pregnancy. The others evaluated TE risk if
      pregnancy was achieved. The rate of TE for 75,141 cycles not resulting in
      pregnancy was not higher than controls in the general population. The three
      studies which compared TE risk when pregnancies were achieved found that ART
      increased the risk for TE primarily during the first trimester. If ovarian
      hyperstimulation syndrome (OHSS) was present the risk increased further. The risk
      for TE after frozen embryo replacement cycles was not increased. CONCLUSIONS: ART
      posed a risk factor for TE during pregnancy, but not during ovarian stimulation
      or in cycles not resulting in pregnancy. Thrombophylaxis is not indicated for all
      women undergoing ART. Women with OHSS should be given thrombophylaxis during the
      acute episode and throughout the first trimester. Caution is advised for patients
      with combined risk factors and treatment should be individualized. Guidelines for
      thromboprophylaxis are provided.

PMID- 28514123
TI  - [Telemedicine: a novel service in pediatric emergency care].
AB  - INTRODUCTION: Telemedicine is a field that deals with monitoring and caring for
      patients who are physically apart from the caregivers, so they cannot communicate
      without technological means. The use of telemedicine has been recognized by a
      number of official organizations worldwide. This article reviews a unique
      service, "pediatrician online", provided by Clalit HMO, through Medtrix Ltd, with
      Schneider Children's Hospital specialists' supervision. With this service,
      parents can receive medical consultation from pediatricians beyond community
      clinic hours. The service is provided by telephone, computer or a mobile
      application, and when possible video calls are made. AIMS: To describe and
      analyze four years of telemedicine experience of the "pediatrician online"
      service. METHODS: A retrospective study was performed including analysis of all
      consultation calls conducted between November 2009 (the beginning of the project)
      and December 2013. Every call to the service was recorded and documented.
      Furthermore, analysis was conducted of follow-up calls to 4% of the applicants in
      order to monitor medical outcome and satisfaction. RESULTS: During the first four
      years approximately half a million consultation calls were provided. The average
      time from referral to obtaining medical advice was eight minutes. The duration of
      the consultation was four and a half minutes on average. Most of the calls were
      related to young children under 4 years (74%), dealing with common pediatric
      problems - fever (23%), respiratory complaints (17%), and gastrointestinal
      problems (12%). One-third of the applicants intended to go to the emergency
      department before they called the service, but only about one-sixth were referred
      at the end of the consultation. Among those referred, only about 60% actually
      went to the emergency department. The use of video-calls has been increasing, and
      reached an average of 30% of the applications. Satisfaction with the service was
      very high according to surveys, scoring 9.8 out of ten. Eighty-two percent of
      patients sampled reported medical improvement on the next day. CONCLUSIONS: There
      is a very high demand for consulting pediatricians beyond clinic hours. The use
      of telemedicine, as provided by the "pediatrician online" service, addresses this
      need safely and effectively with high patient satisfaction. Discussion: The use
      of telemedicine is expected to expand. In order to ensure its proper use while
      recognizing the capabilities and limitations, controlled studies should be
      conducted, exploring the outcome of different approaches in various situations.

PMID- 28514120
TI  - Mouth development.
AB  - A mouth is present in all animals, and comprises an opening from the outside into
      the oral cavity and the beginnings of the digestive tract to allow eating. This
      review focuses on the earliest steps in mouth formation. In the first half, we
      conclude that the mouth arose once during evolution. In all animals, the mouth
      forms from ectoderm and endoderm. A direct association of oral ectoderm and
      digestive endoderm is present even in triploblastic animals, and in chordates,
      this region is known as the extreme anterior domain (EAD). Further support for a
      single origin of the mouth is a conserved set of genes that form a 'mouth gene
      program' including foxA and otx2. In the second half of this review, we discuss
      steps involved in vertebrate mouth formation, using the frog Xenopus as a model.
      The vertebrate mouth derives from oral ectoderm from the anterior neural ridge,
      pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by
      breaking through the body covering in a precise sequence including specification
      of EAD ectoderm and endoderm as well as NC, formation of a 'pre-mouth array,'
      basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane
      perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC,
      while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a
      pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic
      and environmental factors, with understanding guided in part by use of animal
      models. WIREs Dev Biol 2017, 6:e275. doi: 10.1002/wdev.275 For further resources
      related to this article, please visit the WIREs website.

PMID- 28514125
TI  - [LETTERS TO THE EDITOR].

PMID- 28514124
TI  - [PARTIAL BREAST RECONSTRUCTION BY MODIFIED BREAST REDUCTION TECHNIQUES].
AB  - INTRODUCTION: Partial resections of the breast are more than 50% of breast
      oncological surgery. The resulting defect can be substantial and cause meaningful
      deformity that leads to reduced body image satisfaction of the patients,
      affecting their ability to cope with the cancer. Parallel to the development of
      breast oncology techniques, an evolution of breast reconstruction techniques
      occurred. During the last decade, by using techniques from cosmetic breast
      surgery (such as breast reductions, augmentations and mastopexies), we can
      reconstruct extensive partial defects of the breasts at the immediate and delayed
      setting and achieve symmetrical aesthetic results. Of the 350 oncological breast
      surgeries a year performed in our center, 70% undergo partial breast resection
      and only 10% of those surgeries exhibit a defect necessitating reconstruction.
      The recovery and post-operative complications, especially in the immediate
      setting, are significantly reduced in comparison to total breast reconstruction.
      Our experience shows that by using plastic surgery techniques in those
      operations, we can overcome the deformity created by large partial resection of
      the breast and improve the mental recovery from breast cancer.

PMID- 28514126
TI  - [HAPTOGLOBIN POLYMORPHISM AS AN INDEPENDENT PREDICTOR OF DIABETIC NEPHROPATHY AND
      RETINOPATHY].
AB  - INTRODUCTION: The antioxidant protein haptoglobin (Hp) plays a major role in the
      development of diabetic complications such as diabetic nephropathy and
      retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three
      possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their
      biochemical and biophysical properties, such as their antioxidant capacity. The
      Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and
      neutralizing its oxidative potential and the accompanying renal and retinal
      injury. Hence, diabetic patients with different Hp phenotypes have variable
      susceptibility to developing diabetic nephropathy and retinopathy. In diabetes,
      the kidney and the retinal injury progress gradually over time. Thus,
      understanding the factors that mediate the aggravation and progression of these
      complications is of critical importance. One of the latest hypotheses regarding
      the involvement of haptoglobin in the development of diabetic complications is
      its contribution to impaired vitamin D activation in the kidney. Over the last
      few years, great efforts were made in the field to explore this notion and
      decrypt the mechanism behind it. The goal in this area is that the research
      findings will be translated into clinical practice and lead to the development of
      a pharmacogenomics clinical approach that will deal with diabetic complications
      by selective administration of vitamin D according to the Hp genotype.

PMID- 28514127
TI  - [IS IT POSSIBLE TO REDUCE THE INCIDENCE OF CONGENITAL ANOMALIES? ANALYSIS OF
      ADVERSE OBSTETRICS CLINICAL EVENTS].

PMID- 28514128
TI  - [TREATMENT FOR OSTEOARTHRITIS OF THE KNEE].
AB  - INTRODUCTION: Osteoarthritis is the most common joint disorder in the world and
      its incidence is rising. In Western populations it is one of the most frequent
      causes of pain, loss of function and disability in adults. The estimated lifetime
      risk for knee osteoarthritis is approximately 40% in men and 47% in women. The
      diagnosis of osteoarthritis is complex due to a lack of specific physical and/or
      laboratorial findings. The American College of Rheumatology (ACR) has recommended
      using the following criteria for the diagnosis of knee osteoarthritis: chronic
      knee pain (lasting for more than 6 weeks) and at least three of the following: *
      Age over 50 years old. * Morning knee stiffness lasting up to 30 minutes. *
      Crepitus with active motion * Tenderness on bony palpation * Thickening or growth
      of the bones * No local heat on palpation Treatment of osteoarthritis involves
      alleviating pain, attempting to rectify mechanical misalignment, and identifying
      and addressing manifestations of joint instability. The American Academy of
      Orthopedic Surgeons (AAOS) has conducted a systematic review of the current
      scientific and clinical research and has issued clinical practice guidelines
      containing fifteen recommendations for the treatment of osteoarthritis of the
      knee, and include only less invasive alternatives to total or partial knee
      arthroplasty. This review presents the background, diagnosis, treatment and a
      summary of the AAOS guidelines regarding "Treatment of Osteoarthritis of the
      Knee".

PMID- 28514129
TI  - [HAND INJURIES IN ROCK CLIMBERS].
AB  - INTRODUCTION: Rock climbing, whether practiced in nature on cliffs and boulders
      or indoors on walls made of resin and wood, has gained tremendous popularity in
      recent decades. More people are exposed to injuries associated with the unique
      biomechanical forces of rock climbing. A series of repetitive high torque
      movements of the upper limbs are needed to ascend a wall or rockface. These
      movements subject the hand and wrist to large forces, potentially resulting in
      ligament and tendon sprains or rupture and even bone fracture. This review
      describes the anatomy, biomechanics and the common hand injuries in rock
      climbers.

PMID- 28514130
TI  - [MEASURING ADHERENCE TO SELF-CARE GUIDELINES FOR PATIENTS WITH TYPE 2 DIABETES
      WITH DIABETIC ULCERS ADMITTED to THE ORTHOPEDIC REHABILITATION DEPARTMENT AT TEL
      HASHOMER HOSPITAL DURING 2012-2013].
AB  - INTRODUCTION: Diabetic foot is a devastating complication of diabetes and
      represents the major cause of lower limb amputations in the western world in the
      21st century. The World Health Organization predicts a dramatic increase in the
      number of diabetes patients over the next decade and by the year 2025, their
      number is expected to increase to 300 million. AIMS: Examine whether training
      leads to improving performance in the built-in self-care guidelines in patients
      with type 2 diabetes who were hospitalized with diabetic ulcers in the Orthopedic
      Rehabilitation Ward in Tel Hashomer between the years 2012-2013. METHODS: The
      study included 68 type 2 diabetic patients with diabetic ulcer aged 30-80 years,
      regardless of gender, who were hospitalized following a worsening ulcer. The
      research tools included demographic, medical and self-care diligence
      questionnaires and HbA1c measurements in a sugar balance report. RESULTS: Results
      show significant change in eating habits, number of patient measurements
      performed during the week and treatment of the diabetic foot between the
      treatment group and the control group. In addition, support has been found to
      positively affect self-care response. The only variable where no benefit changes
      could be observed was the medicines consumption variable. DISCUSSION:
      Prescriptive guidance, routinely performed, results in improvement in self-care
      among diabetic patients. Mentoring is enabling people to understand the
      importance of carrying out instructions received.

PMID- 28514131
TI  - [TREATMENT OF ACHILLES TENDON RUPTURES].
AB  - INTRODUCTION: Achilles tendon ruptures cause considerable morbidity and
      functionality reduction. There is lack of consensus regarding the best option for
      treatment following acute Achilles tendon rupture. Recent studies have failed to
      show substantial difference in outcome following conservative or operative
      treatment using an early active rehabilitation program. Meta-analyses have shown
      that conservative management has increased the risk of re-rupture, whereas
      operative intervention carries risks of complications related to the wound and
      iatrogenic nerve injury. This article reviews the updated literature-based
      guidelines for the treatment of Achilles tendon tears.

PMID- 28514132
TI  - [ASSESSING THE SHORT AND LONG TERM EFFECT OF VIDEO-ASSISTED THORACIC SURGERY
      LOBECTOMY IN OCTOGENARIAN PATIENTS].
AB  - BACKGROUND: Lung cancer is a leading deadly malignancy, both in men and women,
      with an increasing cancer diagnosis risk with age. Although thoracic surgery
      techniques have evolved and now include Video Assisted Thoracic Surgery (VATS),
      older operable lung cancer patients are still operated on less compared to the
      younger population. This study aimed at investigating the postoperative
      morbidity, mortality, and long-term quality of life in our pool of octogenarian
      patients. METHODS: Octogenarians with newly diagnosed lung cancer at a clinical
      operable stage undergoing VATS procedures were reviewed. All patients had a
      clinical evaluation of their malignant stage. Patients' long-term quality of life
      (QOL) and performance status were evaluated using an institutional telephone
      questionnaire and the Karnofsky score at least 12 months postoperatively.
      RESULTS: Between January 2009 to April 2012, 22 patients underwent VATS lobectomy
      (median age: 82 years). In four cases (18%) the procedure was converted to open
      thoracotomy. Patient follow-up periods ranged from 22 to 52 months. All but one
      patient were released to their homes. Lung malignancy was diagnosed in 19
      patients. Pathological staging ranged from IA to IIB. Three patients had a non
      malignant lung lesion on final pathology. Median postoperative hospital stay was
      6 days. During the first 18 months post-surgery, no mortalities were recorded in
      this case study. The Karnofsky performance score yielded a median of 90. A
      telephone questionnaire revealed that all patients were free of operation-related
      physical limitations. All but one patient described the surgical experience as
      nontraumatic. CONCLUSIONS: Current findings support the belief that today
      surgeons should not deny octogenarian patients the possibility of oncological
      lung surgery based solely on the patients' chronological age.

PMID- 28514133
TI  - [THE INFLUENCE OF THE ISRAELI LEGISLATION ON THE RELATIONSHIP BETWEEN PHYSICIANS
      AND PHARMACEUTICAL COMPANIES].
AB  - INTRODUCTION: The relationship between physicians and pharmaceutical-companies
      raises many dilemmas. There are two types of solutions to these dilemmas: self
      regulation and government regulation. Our goal was to review in what way
      legislative intervention and self-regulation standardize and affect the
      relationship. In addition, we examined the positions of relevant stakeholders
      regarding: 1. The relationship between physicians and pharmaceutical companies;
      2. Future measures we should take to address the ethical dilemmas inherent in
      this relationship. METHODS: 1. In-depth interviews with 42 senior representatives
      of all the relevant stakeholders, with emphasis on their organizational identity,
      since their points of view are influenced and shaped by organizational and
      professional positioning. We analyzed the interviews using the Narralizer
      program. 2. Analysis of three databases: The Ministry of Health, The Israel
      Medical Association and Pharma-Israel, regarding donations made to various
      parties in the health system. RESULTS: The influence of Israeli legislation on
      the relationship between physicians and pharmaceutical companies is almost
      imperceptible. However, in recent years, there have been changes in this
      relationship stemming from international self-regulation, which leads to:
      contractual relationships, decreases in hospitality and tighter internal control
      over this relationship. CONCLUSIONS: Regulation in Israel is not achieving its
      goal satisfactorily. Solutions to reduce the influence of this relationship
      exist. However, the first step is for the regulator to decide to what extent, if
      any, he wants to deal with this issue. If the regulator chooses to take the lead
      on this issue, we will soon face additional legislation that might limit the
      amount of money that the pharmaceutical companies can donate to healthcare
      organizations.

PMID- 28514134
TI  - [WELL-CHILD VISITS REGARDING GROWTH AND DEVELOPMENT OF INFANTS: A CROSS-CULTURAL
      COMPARISON].
AB  - AIMS: 1. To examine the rate of WCV among mothers in four ethno-cultural groups:
      native-born Jewish, Bedouin and immigrants from the Former Soviet Union (FSU) and
      Ethiopia; 2. to test the relationship between WCV in the first and second year of
      the infant's life; 3. to assess the effect of sociodemographic variables on WCV.
      BACKGROUND: Consistent infant well-child visits (WCV) have been found to be
      related to better health status and a decrease in visits to the emergency room
      and hospitalizations. METHODS: The data were collected in the Beer Sheva district
      among community-dwelling women in the years 2010-2012. The quota sample comprised
      of 400 mothers: 100 from each group. The inclusion criteria were: age (18-35
      years old), either first or second child, or age of the youngest child between 18
      24 months. Immigrant mothers lived in Israel for at least 10 years. The
      monitoring of WCV was evaluated according to the registered number of visits in
      the well-baby clinic registration card. RESULTS: Mothers from all groups
      completed fewer WCV than the recommended number. The highest rate of visits was
      observed among the immigrants from the FSU, and the lowest rate among the Bedouin
      mothers (p<.001). Mothers of higher economic status had a higher rate of WCV (b =
      0.38, p < 0.001). The rate of WCV in the second year was a function of the rate
      of WCV in the first year (b = 0.51, p < 0.001). CONCLUSIONS: Medical personnel
      treating infants should address the ethno-cultural and economic background of
      mothers. It is important to give mothers information about preventive medicine at
      an early stage in the infant's life and to encourage mothers in general and
      Bedouin mothers in particular to comply with recommendations regarding WCV.

PMID- 28514135
TI  - Three-Dimensional Hetero-Integration of Faceted GaN on Si Pillars for Efficient
      Light Energy Conversion Devices.
AB  - An important pathway for cost-effective light energy conversion devices, such as
      solar cells and light emitting diodes, is to integrate III-V (e.g., GaN)
      materials on Si substrates. Such integration first necessitates growth of high
      crystalline III-V materials on Si, which has been the focus of many studies.
      However, the integration also requires that the final III-V/Si structure has a
      high light energy conversion efficiency. To accomplish these twin goals, we use
      single-crystalline microsized Si pillars as a seed layer to first grow faceted Si
      structures, which are then used for the heteroepitaxial growth of faceted GaN
      films. These faceted GaN films on Si have high crystallinity, and their threading
      dislocation density is similar to that of GaN grown on sapphire. In addition, the
      final faceted GaN/Si structure has great light absorption and extraction
      characteristics, leading to improved performance for GaN-on-Si light energy
      conversion devices.

PMID- 28514136
TI  - Highly Selective Volatile Organic Compounds Breath Analysis Using a Broadly
      Tunable Vertical-External-Cavity Surface-Emitting Laser.
AB  - A broadly tunable mid-infrared vertical-external-cavity surface-emitting laser
      (VECSEL) is employed in a direct absorption laser spectroscopic setup to measure
      breath acetone. The large wavelength coverage of more than 30 cm-1 at 3.38 MUm
      allows, in addition to acetone, the simultaneous measurement of isoprene,
      ethanol, methanol, methane, and water. Despite the severe spectral interferences
      from water and alcohols, an unambiguous determination of acetone is demonstrated
      with a precision of 13 ppbv that is achieved after 5 min averaging at typical
      breath mean acetone levels in synthetic gas samples mimicking human breath.

PMID- 28514137
TI  - Manifestation of Geometric and Electronic Shell Structures of Metal Clusters in
      Intercluster Reactions.
AB  - Monolayer protected clusters exhibit rich diversity in geometric and electronic
      structures. However, structure-reactivity relationships in these clusters are
      rarely explored. In this context, [Ag44(SR)30]4-, where -SR is an alkyl/aryl
      thiolate, is an interesting system due to its geometrically and electronically
      closed-shell structures and distinct charge states. We demonstrate that these
      structural features of [Ag44(SR)30]4- are distinctly manifested in its solution
      state reaction with another cluster, [Au25(SR)18]-. Through this reaction, an
      alloy cluster anion, [Au12Ag32(SR)30]4-, evolves spontaneously as revealed by
      high-resolution electrospray ionization mass spectrometry. Ultraviolet-visible
      absorption spectroscopy and density functional theory calculations indicate that
      [Au12Ag32(SR)30]4- is formed by the substitution of all of the Ag atoms in the
      innermost icosahedral shell of [Ag44(SR)30]4- and the abundance is attributed to
      its higher stability due to closed geometric as well as electronic shell
      structure, similar to the reactant clusters. We further demonstrate that the
      substitution of metal atoms in the middle dodecahedral shell and the outermost
      mount sites are also possible, however such substitutions produce AuxAg44-x(SR)30
      alloy clusters with geometrically and electronically open shells. Depending on
      specific sites of substitution, an unexpected superatom-nonsuperatom transition
      occurs in the distribution of AuxAg44-x(SR)30 alloy clusters formed in this
      reaction. Our results present a unique example of a structure-reactivity
      relationship in the metal atom substitution chemistry of monolayer protected
      clusters, wherein a systematic trend, reflecting the geometric and the electronic
      shell structures of the reactant as well as the product clusters, was observed.

PMID- 28514138
TI  - Manipulating Ion Migration for Highly Stable Light-Emitting Diodes with Single
      Crystalline Organometal Halide Perovskite Microplatelets.
AB  - Ion migration has been commonly observed as a detrimental phenomenon in
      organometal halide perovskite semiconductors, causing the measurement hysteresis
      in solar cells and ultrashort operation lifetimes in light-emitting diodes. In
      this work, ion migration is utilized for the formation of a p-i-n junction at
      ambient temperature in single-crystalline organometal halide perovskites. The
      junction is subsequently stabilized by quenching the ionic movement at a low
      temperature. Such a strategy of manipulating the ion migration has led to
      efficient single-crystalline light-emitting diodes that emit 2.3 eV photons
      starting at 1.8 V and sustain a continuous operation for 54 h at ~5000 cd m-2
      without degradation of brightness. In addition, a whispering-gallery-mode cavity
      and exciton-exciton interaction in the perovskite microplatelets have both been
      observed that can be potentially useful for achieving electrically driven laser
      diodes based on single-crystalline organometal halide perovskite semiconductors.

PMID- 28514139
TI  - Bioorthogonal Protein Conjugation: Application to the Development of a Highly
      Sensitive Bioluminescent Immunoassay for the Detection of Interferon-gamma.
AB  - Bioorthogonal conjugation eliminates the shortcomings of classical conjugation
      methods. The conjugation of antibodies to reporter proteins, such as
      bioluminescent protein, can be controlled with orthogonal conjugation methods.
      Here we report a bioluminescent immunoassay for the sensitive detection of
      interferon-gamma (IFN-gamma) that utilizes orthogonal conjugation of
      bioluminescent protein, Gaussia luciferase to anti-IFN-gamma antibody. The IFN
      gamma is produced by the immune system and the detection of the IFN-gamma is
      pivotal for the detection of persistent viral and bacterial infections. A
      bioorthogonal conjugation approach is used to conjugate an anti-IFN-gamma
      antibody with a GLuc mutant containing the N-terminal tyrosine using
      formylbenzene diazonium hexafluorophosphate reagent (FBDP) in hydrophilic mild pH
      environment yielding high conjugation efficiency (60%). This reagent is shown to
      be specific for tyrosine (Tyr) residues. Therefore, conjugation through Tyr was
      orthogonal and not detrimental to the bioluminescence activity of GLuc. The
      immunoassay described in this paper is a sandwich type assay and involves a
      capture and a detection antibody. The assay was validated for its robustness,
      precision, accuracy, limit of detection, and recovery.

PMID- 28514140
TI  - Properties of Intermediates in the Catalytic Cycle of Oxalate Oxidoreductase and
      Its Suicide Inactivation by Pyruvate.
AB  - Oxalate:ferredoxin oxidoreductase (OOR) is an unusual member of the thiamine
      pyrophosphate (TPP)-dependent 2-oxoacid:ferredoxin oxidoreductase (OFOR) family
      in that it catalyzes the coenzyme A (CoA)-independent conversion of oxalate into
      2 equivalents of carbon dioxide. This reaction is surprising because binding of
      CoA to the acyl-TPP intermediate of other OFORs results in formation of a CoA
      ester, and in the case of pyruvate:ferredoxin oxidoreductase (PFOR), CoA binding
      generates the central metabolic intermediate acetyl-CoA and promotes a 105-fold
      acceleration of the rate of electron transfer. Here we describe kinetic,
      spectroscopic, and computational results to show that CoA has no effect on
      catalysis by OOR and describe the chemical rationale for why this cofactor is
      unnecessary in this enzymatic transformation. Our results demonstrate that, like
      PFOR, OOR binds pyruvate and catalyzes decarboxylation to form the same
      hydroxyethylidine-TPP (HE-TPP) intermediate and one-electron transfer to generate
      the HE-TPP radical. However, in OOR, this intermediate remains stranded at the
      active site as a covalent inhibitor. These and other results indicate that, like
      other OFOR family members, OOR generates an oxalate-derived adduct with TPP
      (oxalyl-TPP) that undergoes decarboxylation and one-electron transfer to form a
      radical intermediate remaining bound to TPP (dihydroxymethylidene-TPP). However,
      unlike in PFOR, where CoA binding drives formation of the product, in OOR, proton
      transfer and a conformational change in the "switch loop" alter the redox
      potential of the radical intermediate sufficiently to promote the transfer of an
      electron into the iron-sulfur cluster network, leading directly to a second
      decarboxylation and completing the catalytic cycle.

PMID- 28514142
TI  - Nonmonotonic Self-Deformation of Cell Nuclei on Topological Surfaces with
      Micropillar Array.
AB  - Cells respond to the mechanical signals from their surroundings and integrate
      physiochemical signals to initiate intricate mechanochemical processes. While
      many studies indicate that topological features of biomaterials impact cellular
      behaviors profoundly, little research has focused on the nuclear response to a
      mechanical force generated by a topological surface. Here, we fabricated a
      polymeric micropillar array with an appropriate dimension to induce a severe self
      deformation of cell nuclei and investigated how the nuclear shape changed over
      time. Intriguingly, the nuclei of mesenchymal stem cells (MSCs) on the
      poly(lactide-co-glycolide) (PLGA) micropillars exhibited a significant initial
      deformation followed by a partial recovery, which led to an "overshoot"
      phenomenon. The treatment of cytochalasin D suppressed the recovery of nuclei,
      which indicated the involvement of actin cytoskeleton in regulating the recovery
      at the second stage of nuclear deformation. Additionally, we found that MSCs
      exhibited different overshoot extents from their differentiated lineage,
      osteoblasts. These findings enrich the understanding of the role of the cell
      nucleus in mechanotransduction. As the first quantitative report on nonmonotonic
      kinetic process of self-deformation of a cell organelle on biomaterials with
      unique topological surfaces, this study sheds new insight into cell-biomaterial
      interactions.

PMID- 28514141
TI  - Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites.
AB  - A series of analogues based on serine as lead structure were designed, and their
      agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A
      D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced
      variation in subunit-selectivity, potency, and agonist efficacy was observed in a
      manner that was dependent on the GluN2 subunit in the NMDA receptor. In
      particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the
      GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This
      study demonstrates that subunit-selectivity among glycine site NMDA receptor
      agonists can be achieved and suggests that glycine-site agonists can be developed
      as pharmacological tool compounds to study GluN2C-specific effects in NMDA
      receptor-mediated neurotransmission.

PMID- 28514143
TI  - Community-Level Sanitation Coverage More Strongly Associated with Child Growth
      and Household Drinking Water Quality than Access to a Private Toilet in Rural
      Mali.
AB  - Sanitation access can provide positive externalities; for example, safe disposal
      of feces by one household prevents disease transmission to households nearby.
      However, little empirical evidence exists to characterize the potential health
      benefits from sanitation externalities. This study investigated the effect of
      community sanitation coverage versus individual household sanitation access on
      child health and drinking water quality. Using a census of 121 villages in rural
      Mali, we analyzed the association of community latrine coverage (defined by a 200
      m radius surrounding a household) and individual household latrine ownership with
      child growth and household stored water quality. Child height-for-age had a
      significant and positive linear relationship with community latrine coverage,
      while child weight-for-age and household water quality had nonlinear
      relationships that leveled off above 60% coverage (p < 0.01; generalized additive
      models). Child growth and water quality were not associated with individual
      household latrine ownership. The relationship between community latrine coverage
      and child height was strongest among households without a latrine; for these
      households, each 10% increase in latrine coverage was associated with a 0.031 (p
      value = 0.040) increase in height-for-age z-score. In this study, the level of
      sanitation access of surrounding households was more important than private
      latrine access for protecting water quality and child health.

PMID- 28514144
TI  - Water Purification Using Functionalized Cellulosic Fibers with Nonleaching
      Bacteria Adsorbing Properties.
AB  - Portable purification systems are easy ways to obtain clean drinking water when
      there is no large-scale water treatment available. In this study, the potential
      to purify water using bacteria adsorbing cellulosic fibers, functionalized with
      polyelectrolytes according to the layer-by-layer method, is investigated. The
      adsorbed polyelectrolytes create a positive charge on the fiber surface that
      physically attracts and bonds with bacteria. Three types of cellulosic materials
      have been modified and tested for the bacterial removal capacity in water. The
      time, material-water ratio and bacterial concentration dependence, as well as the
      bacterial removal capacity in water from natural sources, have been evaluated.
      Freely dispersed bacteria adsorbing cellulosic fibers can remove greater than
      99.9% of Escherichia coli from nonturbid water, with the most notable reduction
      occurring within the first hour. A filtering approach using modified cellulosic
      fibers is desirable for purification of natural water. An initial filtration test
      showed that polyelectrolyte multilayer modified cellulosic fibers can remove
      greater than 99% of bacteria from natural water. The bacteria adsorbing
      cellulosic fibers do not leach any biocides, and it is an environmentally
      sustainable and cheap option for disposable water purification devices.

PMID- 28514145
TI  - Versatile Construction of 6-Substituted cis-2,8-Dioxabicyclo[3.3.0]octan-3-ones:
      Short Enantioselective Total Syntheses of Cheloviolenes A and B and Dendrillolide
      C.
AB  - A short enantioselective synthesis of 6-substituted cis-2,8
      dioxabicyclo[3.3.0]octan-3-ones is described. The pivotal step is coupling of a
      tertiary radical generated directly from a tertiary alcohol with a 3-chloro-5
      alkoxybutenolide. This strategy is applied toward scalable 14-15 step syntheses
      of three rearranged spongian diterpenoids: cheloviolenes A and B and
      dendrillolide C.

PMID- 28514146
TI  - Accuracy of Explicitly Correlated Local PNO-CCSD(T).
AB  - In recent years PNO-based local correlation methods have gained popularity since
      they allow Coupled Cluster (CC) calculations with reduced computational costs,
      yet only a few systematic studies concerning their accuracy are available, in
      particular for the explicitly correlated versions. In this work we take a deeper
      look at the explicitly correlated local PNO-CCSD(F12*)(T0) and PNO-CCSD(F12*)(T)
      methods. The first variant uses the so-called semicanonical triples correction
      (T0) which neglects off-diagonal elements in the occupied block of the Fock
      matrix. In PNO-CCSD(F12*)(T) this approximation is avoided by means of Laplace
      transformation techniques and convergence to the canonical results in the limit
      of no PNO truncation is restored. We assess the accuracy of both methods using
      well established benchmark sets for reaction energies and weak molecular
      interactions and take a look at a system with strong cooperative many-body
      effects. For reaction energies a close agreement with canonical methods is
      observed, and chemical accuracy can be reached. Also for weak intermolecular
      interactions the accuracy is easily controlled, and the methods even allow for
      improving existing benchmark data.

PMID- 28514147
TI  - Fragmentation of Valence and Core-Shell (Cl 2p) Excited C2Cl4 Molecule.
AB  - The dynamics of the photofragmentation pathways of tetrachloroethylene with
      photon energies from 15 up to 250 eV encompassing the Cl 2p edge is presented. In
      order to distinguish the fragmentation channels, the ionic fragments were
      separated according to their mass-to-charge ratio, measured in coincidence with
      the photoelectrons, and collected as a function of the incident photon energy.
      Distinct minima or maxima are found in the partial ion yield in the region
      between 40 and 50 eV. These features are believed to be associated with the
      Cooper minimum which results from a molecular orbital with a strong atomic 3p
      subshell character. In the shallow core region, some fragmentation patterns are
      considered in terms of fast fragmentation of the C2Cl4 molecule, despite the
      heavy mass of its fragments. In the present case, the fast fragmentation is
      favored by the very strong antibonding character of the LUMO, understandable in
      the frame of the core equivalent model for halogen-containing molecules. In
      addition, ab initio calculations were performed to obtain states at the Cl 2p
      edge. Singlet and triplet states at the Cl 2p edge of the C2Cl4 molecule,
      corresponding to the Cl(2p -> 9b1u*) and Cl(2p -> 8b2u*) transitions, were
      calculated in order to form a basis set of molecular states from which the spin
      orbit splitting can be inferred. Multiconfigurational self-consistent field
      (MCSCF) calculation followed by multireference configuration interaction (MRCI)
      was the method chosen to establish a set of singlet and triplet states at the 2p
      excitation edge in addition to the ground state.

PMID- 28514148
TI  - Hirsutane-Type Sesquiterpenes with Inhibitory Activity of Microglial Nitric Oxide
      Production from the Red Alga-Derived Fungus Chondrostereum sp. NTOU4196.
AB  - The marine red alga Pterocladiella capillacea is an economic alga for the food
      industry in Taiwan, and its associated highly diversified fungi have not been
      investigated meticulously thus far. The EtOAc extract of the fermented broth of
      Chondrostereum sp. NTOU4196, a fungal strain isolated from P. capillacea, was
      found to exhibit significant nitric oxide (NO) production inhibitory activity in
      lipopolysaccharide-activated murine RAW 264.7 cells at a concentration of 100
      MUg/mL in the preliminary screening. Therefore, separation of the active
      principles from the fermented broths was performed, and that has led to the
      isolation of eight new 5,5,5-tricyclic hirsutane-type sesquiterpenes, namely,
      chondroterpenes A-H (1-8), together with seven known analogues. They were
      identified by analyses of spectroscopic data and comparison with literature
      values. Among the new isolates, chondroterpene A (1) exhibited more significant
      NO production inhibitory activity in murine BV-2 microglial cells, and of all the
      isolated compounds, hirsutanol A (9) exerted limited cytotoxic effects and the
      most potent inhibitory activity on NO production.

PMID- 28514149
TI  - Structural and Optical Properties of Subporphyrinoids: A TD-DFT Study.
AB  - Using ab initio approaches accounting for environmental effects, we investigate
      the ground- and excited-state properties of four subporphyrinoids: subporphyrin,
      subporphyrazine, tribenzosubporphyrin, and subphthalocyanine. We first show that
      the selected level of theory, that is DFT(PBE0), is able to reproduce the
      structure and NMR spectra of all compounds. The aromaticity of these four
      macrocyclic entities are next quantified and it is showed that these bowl-shape
      induced molecules present very strong aromatic characters. Next we analyze the
      spectral signatures of all four compounds using an approach going beyond the
      vertical approximation. The 0-0 energies are reproduced with a mean absolute
      deviation smaller than 0.1 eV, and the very good agreement obtained between
      experimental and theoretical band shapes allows us to unravel the vibronic
      contributions responsible to the specific band shapes of these subporphyrinoids.
      Finally, we investigate a large series of substituted subporphyrins, demonstrate
      the quality of the trends that are obtained with theory and design new compounds
      presenting red-shifted optical bands.

PMID- 28514150
TI  - Correction to "Photocycle of Photoactive Yellow Protein in Cell-Mimetic
      Environments: Molecular Volume Changes and Kinetics".

PMID- 28514151
TI  - DeepPPI: Boosting Prediction of Protein-Protein Interactions with Deep Neural
      Networks.
AB  - The complex language of eukaryotic gene expression remains incompletely
      understood. Despite the importance suggested by many proteins variants
      statistically associated with human disease, nearly all such variants have
      unknown mechanisms, for example, protein-protein interactions (PPIs). In this
      study, we address this challenge using a recent machine learning advance-deep
      neural networks (DNNs). We aim at improving the performance of PPIs prediction
      and propose a method called DeepPPI (Deep neural networks for Protein-Protein
      Interactions prediction), which employs deep neural networks to learn effectively
      the representations of proteins from common protein descriptors. The experimental
      results indicate that DeepPPI achieves superior performance on the test data set
      with an Accuracy of 92.50%, Precision of 94.38%, Recall of 90.56%, Specificity of
      94.49%, Matthews Correlation Coefficient of 85.08% and Area Under the Curve of
      97.43%, respectively. Extensive experiments show that DeepPPI can learn useful
      features of proteins pairs by a layer-wise abstraction, and thus achieves better
      prediction performance than existing methods. The source code of our approach can
      be available via http://ailab.ahu.edu.cn:8087/DeepPPI/index.html .

PMID- 28514153
TI  - Efficient DLPNO-CCSD(T)-Based Estimation of Formation Enthalpies for C-, H-, O-,
      and N-Containing Closed-Shell Compounds Validated Against Critically Evaluated
      Experimental Data.
AB  - An accurate and cost-efficient methodology for the estimation of the enthalpies
      of formation for closed-shell compounds composed of C, H, O, and N atoms is
      presented and validated against critically evaluated experimental data. The
      computational efficiency is achieved through the use of the resolution-of
      identity (RI) and domain-based local pair-natural orbital coupled cluster (DLPNO
      CCSD(T)) approximations, which results in a drastic reduction in both the
      computational cost and the number of necessary steps for a composite quantum
      chemical method. The expanded uncertainty for the proposed methodology evaluated
      using a data set of 45 thoroughly vetted experimental values for molecules
      containing up to 12 heavy atoms is about 3 kJ.mol-1, competitive with those of
      typical calorimetric measurements. For the compounds within the stated scope, the
      methodology is shown to be superior to a representative, more general, and widely
      used composite quantum chemical method, G4.

PMID- 28514152
TI  - Hepatoprotective Properties of a Polyphenol-Enriched Fraction from Annona
      crassiflora Mart. Fruit Peel against Diabetes-Induced Oxidative and Nitrosative
      Stress.
AB  - A polyphenol-enriched fraction from Annona crassiflora fruit peel (Ac-Pef)
      containing chlorogenic acid, (epi)catechin, procyanidin B2, and caffeoyl
      glucoside was investigated against hepatic oxidative and nitrosative stress in
      streptozotocin-induced diabetic rats. Serum biochemical parameters, hepatic
      oxidative and nitrosative status, glutathione defense system analysis, and in
      silico assessment of absorption, distribution, metabolism, excretion, and
      toxicity (ADMET) of the main compounds of Ac-Pef were carried out. Ac-Pef
      treatment during 30 days decreased serum alanine aminotransferase, aspartate
      aminotransferase, and alkaline phosphatase activities, as well as hepatic lipid
      peroxidation, protein carbonylation and nitration, inducible nitric oxide
      synthase level, and activities and expressions of glutathione peroxidase,
      superoxide dismutase, and catalase. There were increases in antioxidant capacity,
      glutathione reductase activity, and reduced glutathione level. ADMET predictions
      of Ac-Pef compounds showed favorable absorption and distribution, with no
      hepatotoxicity. A. crassiflora fruit peel showed hepatoprotective properties,
      indicating a promising natural source of bioactive molecules for prevention and
      therapy of diabetes complications.

PMID- 28514154
TI  - Au-Catalyzed [2 + 3] Annulation of Enamides with Propargyl Esters: Total
      Synthesis of Cephalotaxine and Cephalezomine H.
AB  - A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl
      esters has been developed, providing a new method for expeditious assembly of
      synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based
      on this key annulation, strategic installation of the pivotal azaspirocyclic
      core, followed by constructing the benzazepine unit via Witkop cyclization, led
      to the divergent total syntheses of cephalotaxine and cephalezomine H.

PMID- 28514155
TI  - Influence of Monomer Connectivity, Network Flexibility, and Hydrophobicity on the
      Hydrothermal Stability of Organosilicas.
AB  - It is generally assumed that the hydrothermal stability of organically modified
      silica networks is promoted by high monomer connectivity, network flexibility,
      and the presence of hydrophobic groups in the network. In this study a range of
      organosilica compositions is synthesized to explore the extent to which these
      factors play a role in the hydrothermal dissolution of these materials.
      Compositions were synthesized from hexafunctional organically bridged
      silsesquioxanes (OR1)3Si-R-Si(OR1)3 (R = -CH2-, -C2H4-, -C6H12-, -C8H16-, -p-C6H4
      ; R1 = -CH3, -C2H5), tetrafunctional (OEt)2Si(CH3)-C2H4-Si(CH3)(OEt)2 and
      Si(OEt)4, trifunctional silsesquioxanes R'-Si(OMe)3 (R'=CH3, n-C3H7, cyclo-C6H11,
      phenyl), and bifunctional Si(i-C3H7)2(OMe)2. The bond strain, connectivity and
      hydroxyl concentration of all networks were estimated using 29Si cross-polarized
      magic angle spinning nuclear magnetic resonance and Fourier-transform infrared
      spectroscopy. The hydrophilicity was characterized by monitoring the water uptake
      of the materials in moisture treatments with thermogravimetric analysis,
      differential scanning calorimetry, and Fourier-transform infrared spectroscopy.
      The resistance of each network against hydrothermal dissolution in a water/1,5
      pentanediol mixture at 80  degrees C and pH 1, 7, and 13 was analyzed with
      inductively coupled plasma optical emission spectroscopy and X-ray fluorescence.
      Bond strain appears to significantly increase the tendency to dissolve under
      hydrothermal conditions. The stabilizing influences of increased connectivity and
      hydrophobicity were found to be weak.

PMID- 28514156
TI  - Self-Assembly, Hydrogelation, and Nanotube Formation by Cation-Modified
      Phenylalanine Derivatives.
AB  - Fluorenylmethoxycarbonyl-protected phenylalanine (Fmoc-Phe) derivatives are a
      privileged class of molecule that spontaneously self-assemble into hydrogel
      fibril networks. Fmoc-Phe-derived hydrogels are typically formed by dilution of
      the hydrogelator from an organic cosolvent into water, by dissolution of the
      hydrogelator under basic aqueous conditions followed by adjustment of the pH with
      acid, or by other external triggering forces, including sonication and heating.
      These conditions complicate biological applications of these hydrogels. Herein,
      we report C-terminal cation-modified Fmoc-Phe derivatives that are positively
      charged across a broad range of pH values and that can self-assemble and form
      hydrogel networks spontaneously without the need to adjust pH or to use an
      organic cosolvent. In addition, these cationic Fmoc-Phe derivatives are found to
      self-assemble into novel sheet-based nanotube structures at higher
      concentrations. These nanotube structures are unique to C-terminal cationic Fmoc
      Phe derivatives; the parent Fmoc-Phe carboxylic acids form only fibril or worm
      like micelle structures. Nanotube formation by the cationic Fmoc-Phe molecules is
      dependent on positive charge at the C-terminus, since at basic pH where the
      positive charge is reduced only fibrils/worm-like micelles are formed and
      nanotube formation is suppressed. These studies provide an important example of
      Fmoc-Phe derivatives that can elicit hydrogelation without organic cosolvent or
      pH modification and also provide insight into how subtle modification of
      structure can perturb the self-assembly pathways of Fmoc-Phe derivatives.

PMID- 28514158
TI  - Preparation of Carbon Dots for Cellular Imaging by the Molecular Aggregation of
      Cellulolytic Enzyme Lignin.
AB  - Carbon dots, which are less than 10 nm in diameter, have been widely investigated
      because of their unique luminescence properties and potential for use in
      bioimaging. In the present work, natural carbon dots (L-CDs) were obtained by
      molecular aggregation, using ethanol-extracted cellulolytic enzyme lignin. The
      whole process for the preparation of L-CDs was green and simple to operate and
      did not use toxic chemical reagents or harsh conditions. The newly prepared L-CDs
      emitted multicolor photoluminescence following one- and two-photon excitation.
      The L-CDs also showed good cellular biocompatibility, which is crucial for
      biological applications. One- and two-photon cell-imaging studies demonstrated
      the potential of L-CDs for bioimaging.

PMID- 28514157
TI  - Polymersomes with Rapid K+-Triggered Drug-Release Behaviors.
AB  - A novel type of smart polymersomes with rapid K+-triggered drug-release
      properties is developed in this work. Block copolymers with biocompatible
      poly(ethylene glycol) (PEG) as the hydrophilic block and poly(N
      isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB) copolymer as the K+
      responsive block are successfully synthesized. Because of the presence of 18
      crown-6 units, the PEG-b-PNB block copolymers exhibit excellent K+-dependent
      phase-transition behaviors, which show a hydrophilic-hydrophobic state in
      simulated extracellular fluid and present a hydrophilic-hydrophilic state in
      simulated intracellular fluid. Polymersomes with regular spherical shape and good
      monodispersity are prepared by the self-assembly of the PEG-b-PNB block
      copolymers. Both hydrophilic fluorescein isothiocyanate-dextran and hydrophobic
      doxorubicin are selected as model drugs and are successfully encapsulated into
      the PEG-b-PNB polymersomes. After being placed in a simulated intracellular fluid
      with high K+ concentration, the PEG-b-PNB polymersomes immediately disassemble
      accompanied by the rapid and complete release of drugs. Such K+-responsive
      polymersomes with the desired drug-release properties provide a novel strategy
      for advanced intracellular drug delivery and release, which can enhance the
      safety and efficacy of cancer therapy.

PMID- 28514159
TI  - Direct Observation of an Efficient Triplet Exciton Diffusion Process in a
      Platinum-Containing Conjugated Polymer.
AB  - We report the synthesis and characterization of a conjugated polymer incorporated
      with cyclometalated platinum complexes on the main chain. The polymer may serve
      as an efficient triplet sensitizer in light-harvesting systems. The photophysical
      properties of the polymer were studied by nanosecond and femtosecond time
      resolved transient absorption spectroscopies. After excitation, an energy
      transfer process from the thiophene units on the conjugated main chain to the
      singlet excited state of the Pt complex moieties occurred in less than 150 fs.
      The subsequent intersystem crossing process resulted in the formation of a
      triplet excited state at the Pt complex moieties in ~3.2 ps, which was then
      followed by an efficient triplet diffusion process that led to the formation of
      triplet excitons on the polymer main chain in ~283 ps. This proposed efficient
      triplet sensitized polymer system not only enhances the exciton diffusion length
      but also reduces energy loss in the process, which displays remarkable
      implications in the design of novel materials for triplet sensitized solar cells.

PMID- 28514160
TI  - Spatiotemporal Observation of Electron-Impact Dynamics in Photovoltaic Materials
      Using 4D Electron Microscopy.
AB  - Understanding light-triggered charge carrier dynamics near photovoltaic-material
      surfaces and at interfaces has been a key element and one of the major challenges
      for the development of real-world energy devices. Visualization of such dynamics
      information can be obtained using the one-of-a-kind methodology of scanning
      ultrafast electron microscopy (S-UEM). Here, we address the fundamental issue of
      how the thickness of the absorber layer may significantly affect the charge
      carrier dynamics on material surfaces. Time-resolved snapshots indicate that the
      dynamics of charge carriers generated by electron impact in the electron-photon
      dynamical probing regime is highly sensitive to the thickness of the absorber
      layer, as demonstrated using CdSe films of different thicknesses as a model
      system. This finding not only provides the foundation for potential applications
      of S-UEM to a wide range of devices in the fields of chemical and materials
      research, but also has impact on the use and interpretation of electron beam
      induced current for optimization of photoactive materials in these devices.

PMID- 28514162
TI  - Diastereoselective and Branched-Aldehyde-Selective Tandem Hydroformylation
      Hemiaminal Formation: Synthesis of Functionalized Piperidines and Amino Alcohols.
AB  - Starting from readily available allylglycine, a tandem hydroformylation
      hemiaminal formation reaction has been developed for the synthesis of chiral
      functionalized piperidines, with very good diastereoselectivity and branched
      regioselectivity using Rh/(S,S,S)-BOBPHOS catalysts. Tandem hydroformylation
      hemiacetal formation also proceeds with good diastereoselectivity (88:12), with
      the hemiacetal product being hydrogenated with retention of stereochemistry to
      give a chiral intermediate used in the synthesis of the new antibiotic
      nemonoxacin.

PMID- 28514161
TI  - Interdiffusion Reaction-Assisted Hybridization of Two-Dimensional Metal-Organic
      Frameworks and Ti3C2Tx Nanosheets for Electrocatalytic Oxygen Evolution.
AB  - Two-dimensional (2D) metal-organic framework (MOF) nanosheets have been recently
      regarded as the model electrocatalysts due to their porous structure, fast mass
      and ion transfer through the thickness, and large portion of exposed active metal
      centers. Combining them with electrically conductive 2D nanosheets is anticipated
      to achieve further improved performance in electrocatalysis. In this work, we in
      situ hybridized 2D cobalt 1,4-benzenedicarboxylate (CoBDC) with Ti3C2Tx (the
      MXene phase) nanosheets via an interdiffusion reaction-assisted process. The
      resulting hybrid material was applied in the oxygen evolution reaction and
      achieved a current density of 10 mA cm-2 at a potential of 1.64 V vs reversible
      hydrogen electrode and a Tafel slope of 48.2 mV dec-1 in 0.1 M KOH. These results
      outperform those obtained by the standard IrO2-based catalyst and are comparable
      with or even better than those achieved by the previously reported state-of-the
      art transition-metal-based catalysts. While the CoBDC layer provided the highly
      porous structure and large active surface area, the electrically conductive and
      hydrophilic Ti3C2Tx nanosheets enabled the rapid charge and ion transfer across
      the well-defined Ti3C2Tx-CoBDC interface and facilitated the access of aqueous
      electrolyte to the catalytically active CoBDC surfaces. The hybrid nanosheets
      were further fabricated into an air cathode for a rechargeable zinc-air battery,
      which was successfully used to power a light-emitting diode. We believe that the
      in situ hybridization of MXenes and 2D MOFs with interface control will provide
      more opportunities for their use in energy-based applications.

PMID- 28514163
TI  - Palladium-Catalyzed alpha-Stereoselective O-Glycosylation of O(3)-Acylated
      Glycals.
AB  - Pd(MeCN)2Cl2 enables the alpha-stereoselective catalytic synthesis of 2,3
      unsaturated O-glycosides from O(3)-acylated glycals without the requirement for
      additives to preactivate either donor or nucleophile. Mechanistic studies suggest
      that, unlike traditional (eta3-allyl)palladium-mediated processes, the reaction
      proceeds via an alkoxy-palladium intermediate that increases the proton acidity
      and oxygen nucleophilicity of the alcohol. The method is exemplified with the
      synthesis of a range of glycosides and glycoconjugates of synthetic utility.

PMID- 28514165
TI  - Hydrophobic alpha,alpha-Disubstituted Disilylated TESDpg Induces Incipient 310
      Helix in Short Tripeptide Sequence.
AB  - To evaluate the contribution of triethylsilyl alpha,alpha-di-n-propylglycine,
      namely TESDpg, to induce a defined secondary structure, we have prepared model
      tripeptides in which TESDpg was inserted in three different positions. Studies in
      solid state and in solution with adapted techniques showed that TESDpg was able
      to induce a nascent 310 helix in both crystal and solution states.

PMID- 28514166
TI  - A Web Service Framework for Interactive Analysis of Metabolomics Data.
AB  - Analyzing mass spectrometry-based metabolomics data presents a major challenge to
      metabolism researchers, as it requires downloading and processing large data
      volumes through complex "pipelines", even in cases where only a single metabolite
      or peak is of interest. This presents a significant hurdle for data sharing,
      reanalysis, or meta-analysis of existing data sets, whether locally stored or
      available from public repositories. Here we introduce mzAccess, a software system
      that provides interactive, online access to primary mass spectrometry data in
      real-time via a Web service protocol, circumventing the need for bulk data
      processing. mzAccess allows querying instrument data for spectra, chromatograms,
      or two-dimensional MZ-RT areas in either profile or centroid modes through a
      simple, uniform interface that is independent of vendor or instrument type. Using
      a cache mechanism, mzAccess achieves response times in the millisecond range for
      typical liquid chromatography-mass spectrometry (LC-MS) peaks, enabling real-time
      browsing of large data sets with hundreds or even thousands of samples. By
      simplifying access to metabolite data, we hope that this system will help enable
      data sharing and reanalysis in the metabolomics field.

PMID- 28514164
TI  - The Nonbulky DNA Lesions Spiroiminodihydantoin and 5-Guanidinohydantoin
      Significantly Block Human RNA Polymerase II Elongation in Vitro.
AB  - The most common, oxidatively generated lesion in cellular DNA is 8-oxo-7,8
      dihydroguanine, which can be oxidized further to yield highly mutagenic
      spiroiminodihydantoin (Sp) and 5-guanidinohydantoin (Gh) in DNA. In human cell
      free extracts, both lesions can be excised by base excision repair and global
      genomic nucleotide excision repair. However, it is not known if these lesions can
      be removed by transcription-coupled DNA repair (TCR), a pathway that clears
      lesions from DNA that impede RNA synthesis. To determine if Sp or Gh impedes
      transcription, which could make each a viable substrate for TCR, either an Sp or
      a Gh lesion was positioned on the transcribed strand of DNA under the control of
      a promoter that supports transcription by human RNA polymerase II. These
      constructs were incubated in HeLa nuclear extracts that contained active RNA
      polymerase II, and the resulting transcripts were resolved by denaturing
      polyacrylamide gel electrophoresis. The structurally rigid Sp strongly blocks
      transcription elongation, permitting 1.6 +/- 0.5% nominal lesion bypass. In
      contrast, the conformationally flexible Gh poses less of a block to human RNAPII,
      allowing 9 +/- 2% bypass. Furthermore, fractional lesion bypass for Sp and Gh is
      minimally affected by glycosylase activity found in the HeLa nuclear extract.
      These data specifically suggest that both Sp and Gh may well be susceptible to
      TCR because each poses a significant block to human RNA polymerase II
      progression. A more general principle is also proposed: Conformational
      flexibility may be an important structural feature of DNA lesions that enhances
      their transcriptional bypass.

PMID- 28514168
TI  - Regioselective Carbyne Transfer to Ring-Opening Alkyne Metathesis Initiators
      Gives Access to Telechelic Polymers.
AB  - Regioselective carbyne-transfer reagents derived from (3,3,3-trifluoroprop-1-yn-1
      yl)benzene give access to functionalized ring-opening alkyne metathesis
      polymerization (ROAMP) initiators [R-C6H4C=Mo(OC(CH3)(CF3)2)3] featuring electron
      donating or -withdrawing substituents on the benzylidyne. Kinetic studies and
      linear free-energy relationships reveal that the initiation step of the ring
      opening alkyne metathesis polymerization of 5,6,11,12
      tetradehydrobenzo[a,e][8]annulene exhibits a moderate positive Hammett reaction
      constant (rho = +0.36). ROAMP catalysts featuring electron-withdrawing
      benzylidynes not only selectively increase the rate of initiation (ki) over the
      rate of propagation (kp) but also prevent undesired intra- and intermolecular
      chain-transfer processes, giving access to linear poly-(o-phenylene ethynylene)
      with narrow molecular weight distribution. The regioselective carbyne transfer
      methodology and the detailed mechanistic insight enabled the design of a
      bifunctional ROAMP-reversible addition-fragmentation chain-transfer (RAFT)
      initiator complex. ROAMP followed by RAFT polymerization yields hybrid poly-(o
      phenylene ethynylene)-block-poly-(methyl acrylate) block copolymers.

PMID- 28514169
TI  - Engineering Interface Structure to Improve Efficiency and Stability of
      Organometal Halide Perovskite Solar Cells.
AB  - The rapid rise of power conversion efficiency (PCE) of low cost organometal
      halide perovskite solar cells suggests that these cells are a promising
      alternative to conventional photovoltaic technology. However, anomalous
      hysteresis and unsatisfactory stability hinder the industrialization of
      perovskite solar cells. Interface engineering is of importance for the
      fabrication of highly stable and hysteresis free perovskite solar cells. Here we
      report that a surface modification of the widely used TiO2 compact layer can give
      insight into interface interaction in perovskite solar cells. A highest PCE of
      18.5% is obtained using anatase TiO2, but the device is not stable and degrades
      rapidly. With an amorphous TiO2 compact layer, the devices show a prolonged
      lifetime but a lower PCE and more pronounced hysteresis. To achieve a high PCE
      and long lifetime simultaneously, an insulating polymer interface layer is
      deposited on top of TiO2. Three polymers, each with a different functional group
      (hydroxyl, amino, or aromatic group), are investigated to further understand the
      relation of interface structure and device PCE as well as stability. We show that
      it is necessary to consider not only the band alignment at the interface, but
      also interface chemical interactions between the thin interface layer and the
      perovskite film. The hydroxyl and amino groups interact with CH3NH3PbI3 leading
      to poor PCEs. In contrast, deposition of a thin layer of polymer consisting of an
      aromatic group to prevent the direct contact of TiO2 and CH3NH3PbI3 can
      significantly enhance the device stability, while the same time maintaining a
      high PCE. The fact that a polymer interface layer on top of TiO2 can enhance
      device stability, strongly suggests that the interface interaction between TiO2
      and CH3NH3PbI3 plays a crucial role. Our work highlights the importance of
      interface structure and paves the way for further optimization of PCEs and
      stability of perovskite solar cells.

PMID- 28514170
TI  - Discovery of Novel 11-Triazole Substituted Benzofuro[3,2-b]quinolone Derivatives
      as c-myc G-Quadruplex Specific Stabilizers via Click Chemistry.
AB  - The specificity of nucleic acids' binders is crucial for developing this kind of
      drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have
      been developed as G-quadruplex stabilizers with good interactive activities. In
      order to improve the selectivity and binding affinity of quindoline derivatives
      as c-myc G-quadruplex binding ligands, novel triazole containing
      benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using
      the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks.
      The selectivity toward c-myc G-quadruplex DNA of these novel T-BFQs was
      significantly improved, together with an obvious increase on binding affinity.
      Further cellular and in vivo experiments indicated that the T-BFQs showed
      inhibitory activity on tumor cells' proliferation, presumably through the down
      regulation of transcription of c-myc gene. Our findings broadened the
      modification strategies of specific G-quadruplex stabilizers.

PMID- 28514171
TI  - Selective Aerobic C-H Amination of Phenols with Primary Amines over Copper toward
      Benzoxazoles.
AB  - Using O2 as the oxidant, the benzoxazole frameworks can be directly constructed
      from the readily available phenols and primary amines in the presence of NH4PF6
      over copper under mild conditions. Mechanistic studies showed that a novel
      mechanism involving biphenyldiols and o-quinones very possibly takes effect in
      the reaction, because both can selectively give the benzoxazoles under the
      reaction conditions. An unprecedented unstrained Caryl-Caryl bond cleavage takes
      place in the reaction.

PMID- 28514167
TI  - Quantum Dot-Peptide-Fullerene Bioconjugates for Visualization of in Vitro and in
      Vivo Cellular Membrane Potential.
AB  - We report the development of a quantum dot (QD)-peptide-fullerene (C60) electron
      transfer (ET)-based nanobioconjugate for the visualization of membrane potential
      in living cells. The bioconjugate is composed of (1) a central QD electron donor,
      (2) a membrane-inserting peptidyl linker, and (3) a C60 electron acceptor. The
      photoexcited QD donor engages in ET with the C60 acceptor, resulting in quenching
      of QD photoluminescence (PL) that tracks positively with the number of C60
      moieties arrayed around the QD. The nature of the QD-capping ligand also
      modulates the quenching efficiency; a neutral ligand coating facilitates greater
      QD quenching than a negatively charged carboxylated ligand. Steady-state
      photophysical characterization confirms an ET-driven process between the donor
      acceptor pair. When introduced to cells, the amphiphilic QD-peptide-C60
      bioconjugate labels the plasma membrane by insertion of the peptide-C60 portion
      into the hydrophobic bilayer, while the hydrophilic QD sits on the exofacial side
      of the membrane. Depolarization of cellular membrane potential augments the ET
      process, which is manifested as further quenching of QD PL. We demonstrate in
      HeLa cells, PC12 cells, and primary cortical neurons significant QD PL quenching
      (DeltaF/F0 of 2-20% depending on the QD-C60 separation distance) in response to
      membrane depolarization with KCl. Further, we show the ability to use the QD
      peptide-C60 probe in combination with conventional voltage-sensitive dyes (VSDs)
      for simultaneous two-channel imaging of membrane potential. In in vivo imaging of
      cortical electrical stimulation, the optical response of the optimal QD-peptide
      C60 configuration exhibits temporal responsivity to electrical stimulation
      similar to that of VSDs. Notably, however, the QD-peptide-C60 construct displays
      20- to 40-fold greater DeltaF/F0 than VSDs. The tractable nature of the QD
      peptide-C60 system offers the advantages of ease of assembly, large DeltaF/F0,
      enhanced photostability, and high throughput without the need for complicated
      organic synthesis or genetic engineering, respectively, that is required of
      traditional VSDs and fluorescent protein constructs.

PMID- 28514172
TI  - Synthesis of Gold Nanoparticles Using the Interface of an Emulsion Droplet.
AB  - A facile and rapid method for synthesizing single crystal gold spherical or
      platelet (nonspherical) particles is reported. The reaction takes place at the
      interface of two immiscible liquids where the reducing agent decamethylferrocene
      (DmFc) was initially added to hexane and gold chloride (AuCl4-) to an aqueous
      phase. The reaction is spontaneous at room temperature, leading to the creation
      of Au nanoparticles (AuNP). A flow focusing microfluidic chip was used to create
      emulsion droplets, allowing the same reaction to take place within a series of
      microreactors. The technique allows the number of droplets, their diameter, and
      even the concentration of reactants in both phases to be controlled. The size and
      shape of the AuNP are dependent upon the concentration of the reactants and the
      size of the droplets. By tuning the reaction parameters, the synthesized
      nanoparticles vary from nanometer to micrometer sized spheres or platelets. The
      surfactant used to stabilize the emulsion was also shown to influence the
      particle shape. Finally, the addition of other nanoparticles within the droplet
      allows for core@shell particles to be readily formed, and we believe this could
      be a versatile platform for the large scale production of core@shell particles.

PMID- 28514173
TI  - Rh(III)-Catalyzed Regio- and Chemoselective [4 + 1]-Annulation of Azoxy Compounds
      with Diazoesters for the Synthesis of 2H-Indazoles: Roles of the Azoxy Oxygen
      Atom.
AB  - A Rh(III)-catalyzed tandem C-H alkylation/intramolecular decarboxylative
      cyclization of azoxy compounds with diazoesters for the synthesis of 3-acyl-2H
      indazoles is disclosed. The azoxy instead of the azo group enables a distinct
      approach for cyclative capture, leading to a [4 + 1]-annulation rather than a
      classic [4 + 2] manner. The azoxy oxygen atom is traceless after annulation, and
      further removal from the product is not required. This reaction features a
      complete regioselectivity for unsymmetrical azoxybenzenes and a compatibility of
      monoaryldiazene oxides.

PMID- 28514174
TI  - Implications of Occupational Disorder on Ion Mobility in Li4Ti5O12 Battery
      Materials.
AB  - Lithium-titanium-oxide (Li4Ti5O12, LTO) is unique among battery materials due to
      its exceptional cyclability and high rate capability. This performance is
      believed to derive at least partly from the occupational disorder introduced via
      mixed Li/Ti occupancy in the LTO spinel-like structure. We explore the vast
      configuration space accessible during high-temperature LTO synthesis by Monte
      Carlo sampling and indeed find lowest-energy structures to be characterized by a
      high degree of microscopic inhomogeneity. Dynamical simulations in corresponding
      configurations reveal the dominant fraction of Li ions to be immobile on
      nanosecond time scales. However, Ti antisite-like defects stabilized by the
      configurational disorder give rise to a novel correlated ion diffusion mechanism.
      The resulting fast but localized diffusion could be a key element in the sudden
      rise in conductivity found in LTO in the early stages of charging and questions
      the validity of ion mobility measurements for this and other configurationally
      disordered materials.

PMID- 28514175
TI  - Hybrid Model Membrane Combining Micropatterned Lipid Bilayer and Hydrophilic
      Polymer Brush.
AB  - Substrate-supported planar lipid bilayers (SPBs) are being utilized as a
      versatile model system of the biological membrane. However, the proximity between
      the solid support and membrane limits utility of SPBs for the functional analyses
      of membrane proteins. Here, we present a model membrane that can enlarge the
      distance between the substrate surface and the membrane by combining a stable
      scaffold of polymerized lipid bilayer with a hydrophilic polymer brush. A
      micropatterned SPB was generated by the lithographic polymerization of
      diacetylene lipids and subsequent incorporation of natural (fluid) lipid
      bilayers. Hydrophilic polymer brush of poly-2-methacryloyloxyethyl
      phosphorylcholine (poly(MPC)) was formed on the surface of polymeric bilayer by
      the in situ atom transfer radical polymerization (ATRP) in aqueous solution, in
      the presence of embedded fluid lipid bilayers. A model membrane protein
      (Haloquadratum walsbyi bacteriorhodopsin: HwBR) could be reconstituted into the
      polymer brush-supported bilayers with significantly reduced immobile molecules.
      Furthermore, the polymer brush terminals could be functionalized by successively
      polymerizing MPC and 2-aminoethyl methacrylate (AMA). The reactive amine moiety
      of poly(AMA) enables to conjugate a wide range of biological molecules and
      surfaces to the membrane. The combination of micropatterned bilayer and polymer
      brush mimics the two- and three-dimensional structures of the biological
      membrane, providing a platform to assay membrane proteins in a truly biomimetic
      environment.

PMID- 28514176
TI  - Transition-Metal-Free, Visible-Light-Enabled Decarboxylative Borylation of Aryl N
      Hydroxyphthalimide Esters.
AB  - Herein, we report a conceptually novel borylation reaction proceeding via a mild
      photoinduced decarboxylation of redox-activated aromatic carboxylic acids. This
      work constitutes the first application of cheap and easily prepared N
      hydroxyphthalimide esters as aryl radical precursors and does not require the use
      of expensive transition metals or ligands. The reaction is operationally simple,
      scalable, and displays broad scope and functional group tolerance.

PMID- 28514177
TI  - Rh(III)-Catalyzed [4 + 1]-Annulation of Azoxy Compounds with Alkynes: A
      Regioselective Approach to 2H-Indazoles.
AB  - A rhodium-catalyzed regioselective C-H activation/cyclization of azoxy compounds
      with alkynes has been disclosed to construct a variety of 2H-indazoles. A [4 + 1]
      cycloaddition rather than a normal [4 + 2] mode is observed in the process of
      cyclative capture along with an oxygen-atom transfer and a C=C triple bond
      cleavage. This protocol features a broad substrate scope, a good functional group
      tolerance, and an exclusive regioselectivity.

PMID- 28514178
TI  - Defect-Mediated Electron-Hole Separation in One-Unit-Cell ZnIn2S4 Layers for
      Boosted Solar-Driven CO2 Reduction.
AB  - The effect of defects on electron-hole separation is not always clear and is
      sometimes contradictory. Herein, we initially built clear models of two
      dimensional atomic layers with tunable defect concentrations, and hence directly
      disclose the defect type and distribution at atomic level. As a prototype,
      defective one-unit-cell ZnIn2S4 atomic layers are successfully synthesized for
      the first time. Aberration-corrected scanning transmission electron microscopy
      directly manifests their distinct zinc vacancy concentrations, confirmed by
      positron annihilation spectrometry and electron spin resonance analysis. Density
      functional calculations reveal that the presence of zinc vacancies ensures higher
      charge density and efficient carrier transport, verified by ultrafast
      photogenerated electron transfer time of ~15 ps from the conduction band of
      ZnIn2S4 to the trap states. Ultrafast transient absorption spectroscopy manifests
      the higher zinc vacancy concentration that allows for ~1.7-fold increase in
      average recovery lifetime, confirmed by surface photovoltage spectroscopy and PL
      spectroscopy analysis, which ensures promoted carrier separation rates. As a
      result, the one-unit-cell ZnIn2S4 layers with rich zinc vacancies exhibit a
      carbon monoxide formation rate of 33.2 MUmol g-1 h-1, roughly 3.6 times higher
      than that of the one-unit-cell ZnIn2S4 layers with poor zinc vacancies, while the
      former's photocatalytic activity shows negligible loss after 24 h photocatalysis.
      This present work uncovers the role of defects in affecting electron-hole
      separation at atomic level, opening new opportunities for achieving highly
      efficient solar CO2 reduction performances.

PMID- 28514179
TI  - Two-Incision Laparoscopic Cholecystectomy: Reducing Scars in a Simple Way.
AB  - BACKGROUND: About 20% of the population has cholelithiasis and this is the main
      abdominal cause of hospitalization in developed countries. Considering that only
      in the United States about 700,000 cholecystectomies are done each year, it is
      possible to estimate the importance of the problem for public health. OBJECTIVE:
      To describe a two-incision laparoscopic cholecystectomy (TILC) technique using
      only conventional material, without increasing complications or operative time.
      MATERIALS AND METHODS: A consecutive and prospective case series compared to
      another historical operated by conventional laparoscopic cholecystectomy (LC).
      The TILC was performed with three trocars in two incisions, two trocars in
      umbilical incision, and one in epigastrium. RESULTS: A total of 72 patients were
      operated on by the same surgeon (36 in each group). There were no significant
      differences between groups for gender, mean age, body mass index, or length of
      hospital stay. The procedures were classified by the surgeon according to
      surgical difficulty and 58.3% (n = 42) were considered low grade, 9.7% (n = 7)
      difficult, and the other were intermediaries, with no difference between the
      series (P < .05). There were minor complications in 6.94% (n = 5) procedures.
      There were no differences between mean operative time (P = .989), which was 49
      (95% confidence interval [CI] 42-56) minutes in LC and 40 (95% CI 35-44) min in
      TILC. There was no need for additional trocars in any case or for conversion to
      open surgery. CONCLUSIONS: TILC is feasible, safe, and with good aesthetic
      result, using the same instruments of LC, without increasing operative time.

PMID- 28514180
TI  - Molecular Typing of Vibrio parahaemolyticus Strains Isolated from Mollusks in the
      North Adriatic Sea.
AB  - BACKGROUND: Vibrio parahaemolyticus is an emerging foodborne pathogen in the
      Mediterranean, usually associated with shellfish consumption. The increase in the
      number of outbreaks in Europe is primarily associated with the global warming of
      the ocean that has a great impact on the spread and genetic selection of
      waterborne pathogens. The primary role of Italy in Europe's mollusk production,
      together with the fact that cases of infections with V. parahaemolyticus are not
      always notified to the European community, highlighted the necessity of acquiring
      new information about the epidemiological involvement of shellfish products.
      OBJECTIVE: The aim of the study was to provide useful insights into the first
      steps of the Risk Assessment associated with V. parahaemolyticus through the
      molecular characterization of isolates from commercialized mollusks. MATERIALS
      AND METHODS: A total of 102 strains identified as V. parahaemolyticus were
      investigated as part of a larger sampling (1-year survey) from several shellfish
      species collected from the Venice lagoon and the North Adriatic sea. All strains
      were characterized by multilocus sequence typing and tested for the presence of
      virulence genes (trh and tdh). The study of sampling/environmental factors and
      epidemiological analyses was performed to describe the behaviors of the different
      genetic populations. RESULTS: The population structure analysis highlighted three
      genetic clusters that could be subject to temperature selection during cold (<=15
      degrees C) and warm (>16 degrees C) seasons. Moreover, other factors, such as
      molluscan species (clams/mussels), probably played a role in the distribution of
      genetic clusters. Although few strains carried the virulence factors (n = 6
      trh+), epidemiological links with clinical isolates and a local dissemination of
      some sequence types were underlined. CONCLUSION: This work provides a useful
      background on the genotype spread as a first step in the Hazard Identification in
      light of future climate changes.

PMID- 28514181
TI  - Folic Acid Modulates DMBA/TPA-Induced Changes in Skin of Mice: A Study Relevant
      to Carcinogenesis.
AB  - The present study was aimed at investigating the modulatory effects of folic acid
      (FA) on early stages of chemically induced skin cancer. For this, a two-stage
      model of skin tumorigenesis was employed. 7,12-Dimethylbenz(a)anthracene (DMBA,
      500 nmol/100 ul of acetone) was applied topically for two weeks (twice weekly),
      followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly
      for six weeks on the depilated skin of mice, and FA was administered orally at a
      dose of 40 microgram/animal for 10 weeks daily. Balb/c mice were divided into
      four groups depending upon the treatment they received (control, DMBA/TPA, FA,
      and FA+DMBA/TPA). DMBA/TPA treatment led to the formation of papillomas in
      DMBA/TPA and FA+DMBA/TPA groups. Ornithine decarboxylase (ODC), proliferating
      cell nuclear antigen (PCNA), epidermal thickness, and cell count were evaluated
      to assess the beneficial effects in the early stages. FA exhibited its
      ameliorative potential as indicated by decreased epidermal thickness and cell
      count in FA+DMBA/TPA group when compared to DMBA/TPA group. Concomitantly, FA
      decreased the expression of ODC and PCNA in skin and activity of serum lactate
      dehydrogenase, suggesting inhibitory effects on cell proliferation and cell
      damage. Differential modulation in lipid peroxidation and reduced glutathione was
      observed in response to DMBA/TPA treatment and its intervention with FA. Although
      these findings suggest the inhibitory potential of FA during initial stages of
      murine skin cancer, detailed studies are warranted considering the ambiguous
      reports available in literature regarding the association of FA and cancer.

PMID- 28514182
TI  - Aberrant Level of Skp2 and p27KIP1 in Intraductal Proliferative Lesions is
      Associated with Tumorigenesis.
AB  - Breast cancer is one of the leading causes of cancer-related death in women
      worldwide. Here we aimed to examine the expression status of S-phase kinase
      associated protein 2 (Skp2) and p27KIP1, and assess the significance of Skp2 plus
      p27KIP1 expression in patients with intraductal proliferative lesions, including
      ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH). Skp2 and
      p27KIP1 mRNA levels in DCIS, ADH, flat epithelial atypia, and usual ductal
      hyperplasia (UDH) were evaluated by quantitative real-time reverse transcription
      polymerase chain reaction and protein expression was evaluated
      immunohistochemically in 60 fresh tissues and 120 paraffin-embedded tissues from
      patients with the four subtypes above. We found that the protein and mRNA level
      of Skp2 were significantly increased in DCIS and ADH as compared with that in
      UDH. In contrast, p27KIP1 protein and mRNA levels were reduced. Based on the
      above findings, abnormal levels of Skp2 and p27KIP1 have probably been involved
      in the pathogenesis of ADH and DCIS. Thus, Skp2 and p27KIP1 may serve as
      important diagnosis markers.

PMID- 28514184
TI  - Maintenance Lenalidomide for Large-Cell Lymphoma: Who Really Benefits?

PMID- 28514183
TI  - Multigene Panel Testing Provides a New Perspective on Lynch Syndrome.
AB  - Purpose Most existing literature describes Lynch syndrome (LS) as a hereditary
      syndrome leading to high risks of colorectal cancer (CRC) and endometrial cancer
      mainly as a result of mutations in MLH1 and MSH2. Most of these studies were
      performed on cohorts with disease suggestive of hereditary CRC and population
      based CRC and endometrial cancer cohorts, possibly biasing results. We aimed to
      describe a large cohort of mismatch repair (MMR) mutation carriers ascertained
      through multigene panel testing, evaluate their phenotype, and compare the
      results with those of previous studies. Methods We retrospectively reviewed
      clinical histories of patients who had multigene panel testing, including the MMR
      and EPCAM genes, between March 2012 and June 2015 (N = 34,981) and performed a
      series of statistical comparisons. Results Overall, MSH6 mutations were most
      frequent, followed by PMS2, MSH2, MLH1, and EPCAM mutations, respectively. Of 528
      patients who had MMR mutations, 63 (11.9%) had breast cancer only and 144 (27.3%)
      had CRC only. When comparing those with breast cancer only to those with CRC
      only, MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations ( P
      = 2.3 * 10-5). Of the 528 patients, 22.2% met BRCA1 and BRCA2 ( BRCA1/2) testing
      criteria and not LS criteria, and 5.1% met neither BRCA1/2 nor LS testing
      criteria. MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations
      among patients who met BRCA1/2 testing criteria but did not meet LS testing
      criteria ( P = 4.3 * 10-7). Conclusion These results provide a new perspective on
      LS and suggest that individuals with MSH6 and PMS2 mutations may present with a
      hereditary breast and ovarian cancer phenotype. These data also highlight the
      limitations of current testing criteria in identifying these patients, as well as
      the need for further investigation of cancer risks in patients with MMR
      mutations.

PMID- 28514185
TI  - Acute treatment of migraine: quo vadis?

PMID- 28514187
TI  - Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces
      acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic
      effects of antihistaminic drugs.
AB  - An established characteristic of neoplastic cells is their metabolic
      reprogramming, known as the Warburg effect, with greater reliance on
      energetically less efficient pathways (such as glycolysis and pentose phosphate
      shunt) compared with oxidative phosphorylation. This results in an overproduction
      of acidic species that must be extruded to maintain intracellular homeostasis. We
      recently described that blocking the proton currents in leukemic cells mediated
      by Hv1 ion channels triggers a marked intracellular acidification and apoptosis
      induction. Moreover, histamine H1-receptor antagonists were found to induce
      apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T
      cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a
      drop in intracellular pH and cellular viability. This provides evidence of a new
      target structure responsible of the known pro-apoptotic action of antihistaminic
      drugs.

PMID- 28514186
TI  - APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.
AB  - Cells undergoing meiosis produce haploid gametes through one round of DNA
      replication followed by 2 rounds of chromosome segregation. This requires that
      cohesin complexes, which establish sister chromatid cohesion during S phase, are
      removed in a stepwise manner. At meiosis I, the separase protease triggers the
      segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on
      chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase,
      recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it
      from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at
      meiosis II, it was unclear how and when centromeric Rec8 is liberated from its
      protector PP2A. One proposal is that bipolar spindle forces separate PP2A from
      Rec8 as cells enter metaphase II. We show here that sister centromere
      biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast.
      Instead, our data suggest that the ubiquitin-ligase APC/CCdc20 removes PP2A from
      centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1.
      This implies that Rec8 remains protected until entry into anaphase II when it is
      phosphorylated concurrently with the activation of separase. Here, we provide
      further support for this model and speculate on its relevance to mammalian
      oocytes.

PMID- 28514188
TI  - The Invisibility of Mild Traumatic Brain Injury: Impaired Cognitive Performance
      as a Silent Symptom.
AB  - The present study was designed to tackle two notorious features of mild traumatic
      brain injury (mTBI)-heterogeneity and invisibility-by characterizing the full
      scope of mTBI symptoms. Mice were exposed to brain injuries of different
      intensities utilizing a weight-drop model (10, 30, 50, and 70 g) and subsequently
      subjected to a comprehensive battery of behavioral tests at different time points
      and immunohistochemical examination of cortical slices. Whereas the
      physiological, neurological, emotional, and motor function of mTBI mice (i.e.,
      their well-being) remained largely intact, cognitive deficits were identified by
      the y-maze and novel object recognition. Results from these two cognitive tests
      were combined and a dose-response relationship was established between injury
      intensity and cognitive impairment, ranging from an 85% decline after a 70-g
      impact (p < 0.001) to a 20% decline after a 10-g impact (essentially no effect).
      In addition, higher intensities of injury were accompanied by decreased
      expression of axonal and synaptic markers. Thus, our mTBI mice showed a clear
      discrepancy between performance (poor cognitive function) and appearance (healthy
      demeanor). This is of major concern given that diagnosis of mTBI is established
      on the presence of clinical symptoms and emphasizes the need for an alternative
      diagnostic modality.

PMID- 28514189
TI  - Effects of Vaccination with the C-Strain Vaccine on Immune Cells and Cytokines of
      Pigs Against Classical Swine Fever Virus.
AB  - The attenuated C-strain vaccine against classical swine fever virus (CSFV) is one
      of the safest and most effective attenuated vaccines. However, little is known of
      the host immune response after vaccination with the C-strain vaccine. Blood
      samples from vaccinated pigs were collected to evaluate the number of immune
      cells, the level of specific CSFV antibody, and related cytokines induced by the
      vaccination of C-strain vaccine. The C-strain nucleic acid was gradually removed
      and specific antibody to vaccine kept increasing; the amount of the lymphocyte,
      Tc cell, and Th cell increased; some inflammatory cytokines such as interleukin
      (IL)-1 and tumor necrosis factor-alpha mainly showed downregulated trends, but IL
      6 and IL-8 were upregulated greatly; IL-2, IL-4, IL-5, IL-12p40, IL-13,
      interferon (IFN)-I, and Toll-like receptors (TLRs) kept high expression level
      after 28 days postvaccination (dpv); IFN-gamma was upregulated slightly at 5 and
      9 dpv, respectively. These results suggest that the C-strain vaccine induces a
      Th2 cell response to produce the specific antibody. The vaccine virus replicates
      at very low level. C-strain vaccine burden has close relationship with the
      expression of TLRs. The overexpression of TLRs initiates the innate immune system
      to clear up the vaccine. Meanwhile, ILs expressed by immune system induce the
      differentiation of B cells and produce specific antibody.

PMID- 28514191
TI  - Commentary on Some Recent Theses Relevant to Combating Aging: June 2017.

PMID- 28514190
TI  - Criterion-Referenced Fitness Standards Associated with Maintaining Functional
      Capacity in Chilean Older Adults.
AB  - The aim of the current study was to develop fitness standards associated with
      maintaining physical capacity in older adults at two different levels-that needed
      for advanced functioning and that needed for maintaining moderate (independent)
      functional ability. This was a cross-sectional study of 406 Chilean adults aged
      60 and more. Functional capacity was measured through the Composite Physical
      Function (CPF) scale. A battery of validated fitness tests for this population
      was used. Based on the results of the CPF, two variables were created: "advanced
      physical capacity" (defined as those scoring 24 on the CPF scale) and "moderate
      (independent) physical capacity," defined as those scoring between 14 and 23 on
      the CPF scale. Fitness cut-off values were calculated for each of the two created
      variables to evaluate the risk of losing the independence through Receiver
      Operating Characteristic (ROC) curves analysis and logistic regression. The
      developed cut-off points provide important information for professionals working
      directly with older adults, to detect the risk of losing functionality and
      independence.

PMID- 28514192
TI  - Diagnostic and Treatment Patterns Among Children, Adolescents, and Young Adults
      with Thyroid Cancer in Ontario: 1992-2010.
AB  - BACKGROUND: Thyroid carcinoma is rare in young children, with a sharp increase in
      incidence among adolescents and young adults between 15 and 29 years of age. The
      incidence of thyroid carcinoma is increasing worldwide. Limited prospective
      population-based data are available to describe diagnostic and treatment
      practices in this age group. This study undertook a population-based review of
      thyroid carcinoma among 0- to 29-year-old individuals in Ontario, Canada,
      utilizing linked administrative data to describe the demographic and care
      patterns over nearly two decades. METHODS: Cases from the Ontario Cancer Registry
      were identified and linked to administrative data sources at the Institute for
      Clinical Evaluative Sciences. Cases diagnosed prior to a patient's 30th birthday
      between 1992 and 2010 were considered eligible. Billing records identified
      ultrasonography, fine-needle aspiration biopsy, radioiodine therapy, and surgical
      approach. RESULTS: A total of 2552 patients aged 0-29 years were diagnosed with
      thyroid carcinoma during the study period. There was a 2.1-fold increase in
      standardized incidence rate over the 19 years of this study. Thyroid carcinoma
      was diagnosed subsequent to a prior malignancy in 47/2552 patients at a median
      interval of 11.6 years after initial cancer diagnosis. Seventeen individuals
      developed a second malignancy after treatment for thyroid carcinoma. Most
      patients (90.44%) underwent preoperative ultrasound (ranging from 1 to 13
      preoperative studies). Preoperative thyroid scintigraphy was used in 44% of
      patients, with a significant decline in usage over the study period. Fine-needle
      aspiration biopsy usage rose by 20% over the study period, although 26% of
      patients had no biopsy prior to surgery. Primary total thyroidectomy followed by
      two-stage thyroidectomy were the most frequently performed procedures, and 56% of
      patients received therapeutic radioiodine. CONCLUSIONS: This study establishes a
      foundation of diagnostic and practice patterns over nearly two decades. The study
      corroborates, in the Ontario population, the rising incidence of thyroid
      carcinoma in children and adolescents and young adults. Finally, it identifies
      the use of multiple preoperative ultrasound studies, low rates of thyroid biopsy,
      and thyroid scintigraphy as targets to improve efficiencies of care and to reduce
      unnecessary healthcare expenditures through education, standardization of
      diagnostic approach, and possibly regionalization of care.

PMID- 28514195
TI  - Analysis of the Use and Impact of Twitter During American Society of Clinical
      Oncology Annual Meetings From 2011 to 2016: Focus on Advanced Metrics and User
      Trends.
AB  - PURPOSE: The use of social media, in particular Twitter, has substantially
      increased among health care stakeholders in the field of hematology and oncology,
      with an especially sharp increase in the use of Twitter during times of major
      national meetings. The most attended meeting in the oncology field is the ASCO
      annual meeting. Little is known about the detailed metrics involved in the use,
      volume, and impact of Twitter during the ASCO annual meeting. METHODS: We
      conducted a retrospective review of tweets during the ASCO annual meetings from
      2011 to 2016. The total data set encompassed 190,732 tweets from 39,745 authors
      over six consecutive ASCO meetings from 2011 to 2016 (inclusive). Tweets, all
      publically available, were collected by Nephrology On-Demand Analytics. RESULTS:
      The number of individual authors increased from 1,429 during the 2011 ASCO
      meeting to 15,796 during the 2016 ASCO meeting, an 11-fold increase over the
      total 5-year period. There was a notable increase in tweets from the 2011 ASCO
      meeting (n = 7,746) to the 2016 ASCO meeting (n = 72,698), a nine-fold increase
      during the study period. The most commonly tweeted term or topic changed over
      time, generally reflecting the breakthroughs of each designated year; these terms
      were "melanoma" for both the 2011 and 2012 ASCO meetings; "breast cancer" for the
      2013 ASCO meeting; "lung cancer" for the 2014 ASCO meeting; and "ImmunOnc" or
      "immunotherapy/immuno-oncology" for both the 2015 and 2016 ASCO meetings.
      CONCLUSION: The use of Twitter among health care stakeholders during the ASCO
      meeting has markedly increased over time, demonstrating the increasing role of
      social media in the dissemination of findings at the most highly attended
      hematology and oncology conference of the year.

PMID- 28514196
TI  - Interactions Between NS1 of Influenza A Viruses and Interferon-alpha/beta:
      Determinants for Vaccine Development.
AB  - Influenza A viruses (IAVs) cause mild to severe infections in humans with
      considerable socioeconomic and global health consequences. The host interferon
      (IFN)-alpha/beta response, critical as the first line of defense against foreign
      pathogens, is induced upon detection of IAV genomic RNA in infected cells by host
      innate pattern recognition receptors. IFN-alpha/beta production and subsequent
      activation of cell signaling result in the expression of antiviral IFN-stimulated
      genes whose products target various stages of the IAV life cycle to inhibit viral
      replication and the spread of infection and establish an antiviral state. IAVs,
      however, encode a multifunctional virulence factor, nonstructural protein 1
      (NS1), that directly antagonizes the host IFN-alpha/beta response to support
      viral replication. In this review, we highlight the mechanisms by which NS1
      suppresses IFN-alpha/beta production and subsequent cell signaling, and consider,
      therefore, the potential for recombinant IAVs lacking NS1 to be used as live
      attenuated vaccines.

PMID- 28514193
TI  - 90-90-90-Plus: Maintaining Adherence to Antiretroviral Therapies.
AB  - Medication adherence is the "Plus" in the global challenge to have 90% of HIV
      infected individuals tested, 90% of those who are HIV positive treated, and 90%
      of those treated achieve an undetectable viral load. The latter indicates viral
      suppression, the goal for clinicians treating people living with HIV (PLWH). The
      comparative importance of different psychosocial scales in predicting the level
      of antiretroviral adherence, however, has been little studied. Using data from a
      cross-sectional study of medication adherence with an international convenience
      sample of 1811 PLWH, we categorized respondent medication adherence as None (0%),
      Low (1-60%), Moderate (61-94%), and High (95-100%) adherence based on self
      report. The survey contained 13 psychosocial scales/indices, all of which were
      correlated with one another (p < 0.05 or less) and had differing degrees of
      association with the levels of adherence. Controlling for the influence of race,
      gender, education, and ability to pay for care, all scales/indices were
      associated with adherence, with the exception of Berger's perceived stigma scale.
      Using forward selection stepwise regression, we found that adherence self
      efficacy, depression, stressful life events, and perceived stigma were
      significant predictors of medication adherence. Among the demographic variables
      entered into the model, nonwhite race was associated with double the odds of
      being in the None rather than in the High adherence category, suggesting these
      individuals may require additional support. In addition, asking about self
      efficacy, depression, stigma, and stressful life events also will be beneficial
      in identifying patients requiring greater adherence support. This support is
      essential to medication adherence, the Plus to 90-90-90.

PMID- 28514197
TI  - Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell
      Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.
AB  - PURPOSE: To investigate the change of serum IgG4 concentrations correlated with
      clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma
      associated with IgG4-related ophthalmic disease (IgG4-ROD). METHODS: Three
      consecutive patients with histopathologically confirmed ocular adnexal marginal
      zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients
      received radiotherapy and 1 patient received steroid therapy. Treatment outcome
      was evaluated by clinical symptoms, radiologic examination, and change of serum
      IgG4 level in these patients. RESULTS: All patients had elevated serum IgG4
      before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who
      received radiotherapy achieved complete remission and the serum IgG4 decreased to
      345 and 92 mg/dL, respectively. The patient who underwent systemic steroid
      achieved partial remission and the serum IgG4 decrease to 161 mg/dL. CONCLUSION:
      Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal
      zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum
      IgG4 may decrease or keep stable after treatment, accompanied by improvement in
      clinical symptoms and reduction of lesions.

PMID- 28514199
TI  - Drawing asthma: An exploration of patients' perceptions and experiences.
AB  - OBJECTIVE: As an art form, drawings can facilitate the tangible expression of
      patients' inner images and feelings in a range of health conditions. However,
      there are currently no published studies investigating adults' perspectives of
      asthma using drawings. This study aimed to explore how adults' drawings
      illustrate their perceptions and experiences of asthma. METHODS: Adults with
      asthma participated in a one-on-one drawing activity. Analysis was grounded in
      the participants' accounts of their drawing, which were examined alongside the
      relevant image. A coding approach was used to cluster thematic material and map
      the data according to the Common-Sense Model of Self-Regulation (CSM). RESULTS:
      Eighteen participants took part. Three themes emerged: (1) asthma is constrictive
      and restrictive, (2) feeling alone, feeling different, and (3) the life journey
      of asthma. The drawings aligned with several domains of the CSM, in particular
      consequences. The images drawn by the participants and their subsequent
      discussions highlighted the prominence of the emotional burden of asthma.
      CONCLUSIONS: The drawings provided powerful and evocative communication of the
      experience of asthma. Future research using drawings can further both healthcare
      professionals' and patients' understanding of the physical, social and emotional
      demands of living with asthma, and support the development of asthma self
      management practices.

PMID- 28514198
TI  - Piceatannol Reduces Fat Accumulation in Caenorhabditis elegans.
AB  - Excess fat accumulation and abnormal metabolism are involved in numerous diseases
      and thus the research on identification of compounds that can regulate energy
      homeostasis could significantly facilitate the current effort to prevent and/or
      treat metabolic disorders. Piceatannol, one of the natural stilbenes, was
      previously found to decrease lipid accumulation of 3T3-L1 adipocytes. However,
      its role in fat metabolism in vivo is not known. Thus, Caenorhabditis elegans as
      an animal model was used in the current study to determine the effect of
      piceatannol on fat accumulation and its underlying mechanisms. The results showed
      that 50 and 100 MUM piceatannol significantly reduced fat accumulation of wild
      type worms grown in normal and high-glucose conditions without altering the
      growth rate, worm length, pumping rate, or moving speed. The current study
      further indicated that piceatannol decreased the expression of sbp-1 (encodes an
      ortholog of mammalian sterol regulatory element-binding protein) and its target
      gene fasn-1 (encodes an ortholog of fatty acid synthase) as well as increased the
      expression of hosl-1 (encodes an ortholog of hormone-sensitive lipase) in glucose
      treated worms. These data suggested that piceatannol reduced fat accumulation in
      C. elegans by suppression of genes involved in lipid synthesis and possibly
      through stimulation of lipolysis. Given that piceatannol exerts similar effects
      in both C. elegans and 3T3-L1 cells, our finding could provide a mechanistic
      insight into the role of piceatannol in lipid metabolism in mammals.

PMID- 28514200
TI  - Culturally Competent Sexual Healthcare as a Prerequisite for Obtaining
      Preexposure Prophylaxis: Findings from a Qualitative Study.
AB  - PURPOSE: Men who have sex with men (MSM) experience stigma in healthcare
      settings, which impedes disclosure of sexual behavior, potentially limiting
      uptake of preexposure prophylaxis (PrEP). The purpose of this study was to
      describe the context of this limitation and explore geographical variability.
      METHODS: To understand how discomfort in healthcare settings affects PrEP
      utilization, we conducted two online focus groups with geographically diverse
      samples of MSM. RESULTS: Respondents identified primary care providers as
      preferred sources for PrEP, but potential uptake was limited by barriers to
      establishing nonjudgmental relationships with these providers. CONCLUSION:
      Improved patient-provider communication about sexual behaviors might increase
      PrEP use among MSM.

PMID- 28514202
TI  - The physical characteristics of match-play in English schoolboy and academy rugby
      union.
AB  - The aim was to compare the physical characteristics of under-18 academy and
      schoolboy rugby union competition by position (forwards and backs). Using a
      microsensor unit, match characteristics were recorded in 66 players. Locomotor
      characteristics were assessed by maximum sprint speed (MSS) and total, walking,
      jogging, striding and sprinting distances. The slow component (<2 m . s-1) of
      PlayerLoadTM (PLslow), which is the accumulated accelerations from the three axes
      of movement, was analysed as a measure of low-speed activity (e.g., rucking). A
      linear mixed-model was assessed with magnitude-based inferences. Academy forwards
      and backs almost certainly and very likely covered greater total distance than
      school forwards and backs. Academy players from both positions were also very
      likely to cover greater jogging distances. Academy backs were very likely to
      accumulate greater PLslow and the academy forwards a likely greater sprinting
      distance than school players in their respective positions. The MSS, total,
      walking and sprinting distances were greater in backs (likely-almost certainly),
      while forwards accumulated greater PLslow (almost certainly) and jogging distance
      (very likely). The results suggest that academy-standard rugby better prepares
      players to progress to senior competition compared to schoolboy rugby.

PMID- 28514204
TI  - Factors influencing influenza vaccination among South Korean adult asthma
      patients: A nationwide population-based cross-sectional study.
AB  - BACKGROUND: It is important to identify factors associated with influenza
      vaccination. This study was performed to investigate factors associated with
      vaccination coverage among asthma patients in Korea. METHODS: Data were obtained
      from 229,121 participants (5,989 with asthma and 223,132 without asthma) in the
      2010 Korean Community Health Survey. The demographic characteristics and
      socioeconomic status of respondents with and without asthma were compared.
      Univariate and multiple logistic regression analyses were used to evaluate
      socioeconomic status and other demographic variables potentially related to
      influenza vaccination in asthma patients. RESULTS: The vaccination rates of young
      (19-49 years) and middle-aged (50-64 years) asthma patients were only 28.3 and
      49.5%, respectively, whereas that of elderly (>=65 years) asthma patients was
      81.5%. After regression, older age (odds ratio [OR], 5.53; 95% confidence
      interval [95% CI], 3.56-8.59), poor self-rated health status (OR, 1.43; 95% CI,
      1.01-2.03), and regular health check-ups (OR, 2.07, 95% CI, 1.64-2.60) were
      associated with increased influenza vaccination rates in asthma patients.
      CONCLUSIONS: It is important to improve influenza vaccination coverage for non
      elderly patients with asthma, especially those who do not engage in regular
      exercise or undergo regular health check-ups and those who consider themselves to
      be healthy.

PMID- 28514205
TI  - APJ Is Associated with Treatment Response in Gastric Cancer Patients Receiving
      Concurrent Chemoradiotherapy and Endostar Therapy.
AB  - BACKGROUND: Endostar combined with concurrent chemoradiotherapy (CRT) has been
      used in patients with gastric cancers (GCs). However, there are no reliable
      markers to predict the treatment response and prognosis of these patients. Apelin
      and its receptor (APJ) are involved in angiogenesis in tumor tissues. We aimed to
      study whether Apelin and Apelin receptor (APJ) tumor expression can predict the
      treatment response of combination therapy of endostar and CRT. MATERIALS AND
      METHODS: We enrolled patients with locally advanced GC receiving CRT only and
      CRT+endostar combination therapy. Apelin receptor (APJ) in tumor samples was
      determined by immunohistological staining and scored by measuring staining area
      and signal intensity. RESULTS: The high APJ expression has significantly higher
      rates of tumor invasion, local lymph node, and distant metastasis (all p <
      0.001). In the CRT only group, the distribution of high and low APJ expression in
      patients with good and poor treatment response to CRT is not significantly
      different (p = 0.235). However, in the CRT+endostar group, the chance of having
      poor response to combined treatment is 3.645-fold higher in those having high APJ
      expression levels than those who have low APJ expression levels. Our prognostic
      analysis shows that in the CRT+endostar group, high APJ expression had
      significantly shorter overall survival (OS) period than those with low APJ
      expression (p < 0.001). Furthermore, multivariate survival analysis reveals that
      the APJ expression is an independent predictor for the OS period in GC patients
      treated with CRT+endostar. CONCLUSION: Tumor APJ can be used to predict the
      therapy response and prognosis in GC patients receiving CRT+endostar therapy.

PMID- 28514203
TI  - Cost-effectiveness of MR Imaging-guided Strategies for Detection of Prostate
      Cancer in Biopsy-Naive Men.
AB  - Purpose To evaluate the cost-effectiveness of multiparametric diagnostic magnetic
      resonance (MR) imaging examination followed by MR imaging-guided biopsy
      strategies in the detection of prostate cancer in biopsy-naive men presenting
      with clinical suspicion of cancer for the first time. Materials and Methods A
      decision-analysis model was created for biopsy-naive men who had been recommended
      for prostate biopsy on the basis of abnormal digital rectal examination results
      or elevated prostate-specific antigen levels (age groups: 41-50 years, 51-60
      years, and 61-70 years). The following three major strategies were evaluated: (a)
      standard transrectal ultrasonography (US)-guided biopsy; (b) diagnostic MR
      imaging followed by MR imaging-targeted biopsy, with no biopsy performed if MR
      imaging findings were negative; and (c) diagnostic MR imaging followed by MR
      imaging-targeted biopsy, with a standard biopsy performed when MR imaging
      findings were negative. The following three MR imaging-guided biopsy strategies
      were further evaluated in each MR imaging category: (a) biopsy with cognitive
      guidance, (b) biopsy with MR imaging/US fusion guidance, and (c) in-gantry MR
      imaging-guided biopsy. Model parameters were derived from the literature. The
      primary outcome measure was net health benefit (NHB), which was measured as
      quality-adjusted life-years (QALYs) gained or lost by investing resources in a
      new strategy compared with a standard strategy at a willingness-to-pay (WTP)
      threshold of $50 000 per QALY gained. Probabilistic sensitivity analysis was
      performed by using Monte Carlo simulations. Results Noncontrast MR imaging
      followed by cognitively guided MR biopsy (no standard biopsy if MR imaging
      findings were negative) was the most cost-effective approach, yielding an
      additional NHB of 0.198 QALY compared with the standard biopsy approach.
      Noncontrast MR imaging followed by in-gantry MR imaging-guided biopsy (no
      standard biopsy if MR imaging findings were negative) led to the highest NHB gain
      of 0.251 additional QALY compared with the standard biopsy strategy. All MR
      imaging strategies were cost-effective in 94.05% of Monte Carlo simulations.
      Analysis by age groups yielded similar results. Conclusion MR imaging-guided
      strategies for the detection of prostate cancer were cost-effective compared with
      the standard biopsy strategy in a decision-analysis model. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 28514206
TI  - First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with
      Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study.
AB  - 44Sc is a promising positron emission tomography (PET) radionuclide (T1/2 = 4.04
      hours, Ebeta+average = 632 keV) and can be made available, using a cyclotron
      production route, in substantial quantities as a highly pure product. Herein, the
      authors report on a first-in-human PET/CT study using 44Sc-DOTATOC prepared with
      cyclotron-produced 44Sc. The production of 44Sc was carried out through the
      44Ca(p,n)44Sc nuclear reaction at Paul Scherrer Institut, Switzerland. After
      separation, 44Sc was shipped to Zentralklinik Bad Berka, Germany, where
      radiolabeling was performed, yielding radiochemically pure 44Sc-DOTATOC. Two
      patients, currently followed up after peptide receptor radionuclide therapy of
      metastatic neuroendocrine neoplasms, participated in this proof-of-concept study.
      Blood sampling was performed before and after application of 44Sc-DOTATOC. PET/CT
      acquisitions, performed at different time points after injection of 44Sc-DOTATOC,
      allowed detection of even very small lesions on delayed scans. No clinical
      adverse effects were observed and the laboratory hematological, renal, and
      hepatic profiles remained unchanged. In this study, cyclotron-produced 44Sc was
      used in the clinic for the first time. It is attractive for theranostic
      application with 177Lu, 90Y, or 47Sc as therapeutic counterparts. 44Sc-based
      radiopharmaceuticals will be of particular value for PET facilities without
      radiopharmacy, to which they can be shipped from a centralized production site.

PMID- 28514207
TI  - Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell
      Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy.
AB  - Abnormal autophagy regulation affects the chemoresistance of ovarian cancer,
      during which the circadian gene clock may play a major role. In this study, RNA
      interference plasmid pSUPER-Clock and overexpression plasmid pcDNA3.1-Clock of
      CLOCK were used to stably transfect the SKOV3/DDP cells by lipofection. Upon
      screening, the in vitro transfected cell lines with pSUPER-Clock, the autophagy
      level, and G0/G1 phase cells were significantly reduced, and the expression
      levels of Clock, LC3, P-gp, and MRP2 were inhibited. In contrast, the autophagy
      level and G0/G1 phase cells in cell lines transfected with pcDNA3.1-Clock were
      significantly increased, and the expressions of Clock, LC3, P-gp, and MRP2 were
      enhanced. In comparison with the untransfected control group showed the
      percentage of apoptotic cells in SKOV3/DDP cell lines of Clock interfering
      expression group after cisplatin treatment was significantly increased while the
      survival was substantially reduced. These results indicated that inhibiting the
      circadian gene Clock expression can reverse the cisplatin resistance of ovarian
      cancer SKOV3/DDP cell lines by affecting the protein expression of drug
      resistance genes during which autophagy plays an important role. The CLOCK gene
      may be designated as a novel candidate for targeted gene therapy in drug
      resistant ovarian cancer.

PMID- 28514208
TI  - Clinical Significance and Tumor-Suppressive Function of miR-516b in Nonsmall Cell
      Lung Cancer.
AB  - BACKGROUND: MicroRNA-516b (miR-516b) has been recently reported to be
      downregulated in nonsmall cell lung cancer (NSCLC). However, its clinical
      significance and biological function in NSCLC remain to be clarified. MATERIALS
      AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used
      to detect the expression of miR-516b in 82 paired fresh primary tumor tissues and
      NSCLC cell lines. The association of miR-516b expression with clinicopathological
      factors and prognosis was statistically analyzed by SPSS 21.0 software, Kaplan
      Meier method, and Cox regression analyses. Cell Counting Kit-8, colony formation,
      flow cytometric, Transwell migration, and invasion assays were used to evaluate
      the proliferation, cell cycle, apoptosis, migration, and invasion of NSCLC cells
      after miR-516b mimics or negative control of mimics transfection. RESULTS: The
      expression level of miR-516b was found to be significantly lower in NSCLC tissues
      and cell lines than in corresponding normal tissues and cells. Decreased miR-516b
      expression was significantly associated with tumor size (p = 0.004), Tumor Node
      Metastasis (TNM) stage (p = 0.016), and shorter overall survival (p = 0.0039).
      Multivariate analysis suggested that miR-516b was an independent risk factor for
      NSCLC (hazard ratio = 2.435, 95% confidence interval: 1.423-2.457; p = 0.003).
      Furthermore, overexpression of miR-516b could inhibit NSCLC cell proliferation,
      cell cycle progression, migration and invasion, and promoted cell apoptosis. The
      qRT-PCR results indicated that overexpressing miR-516b reduced the mRNA
      expression of CDK2, MMP-2, and MMP-9, whereas increased BAX mRNA expression in
      NSCLC cells. Their protein expression levels presented similar trends, as
      confirmed by Western blotting. CONCLUSIONS: Findings in this study demonstrated
      for the first time that miR-516b expression might be a novel diagnostic and
      prognostic factor, as well as a promising target for NSCLC.

PMID- 28514209
TI  - Cancer Biotherapy: More Than Immunotherapy.

PMID- 28514210
TI  - Systemic Effects of Local Tumor Ablation: Oncogenesis and Antitumor Induced
      Immunity.

PMID- 28514211
TI  - Diagnostic Performance of Self-navigated Whole-Heart Contrast-enhanced Coronary 3
      T MR Angiography.

PMID- 28514212
TI  - Dynamic Contrast-enhanced MR Imaging of Advanced Hepatocellular Carcinoma:
      Comparison with the Liver Parenchyma and Correlation with the Survival of
      Patients Receiving Systemic Therapy.

PMID- 28514213
TI  - Liver Surface Nodularity as a Biomarker for Detection and Evaluation of
      Cirrhosis.

PMID- 28514214
TI  - Imaging of Acute Capsuloligamentous Sports Injuries in the Ankle and Foot: Sports
      Imaging Series.
AB  - The ankle and foot are commonly injured during sporting activities. Clinical
      diagnosis can at times be challenging, due to the complex anatomy and multiple
      sites of potential injury. In the athlete, there is a reduced threshold for
      imaging to clarify diagnosis, guide prognosis, and treatment. Diagnostic imaging
      is also helpful in evaluating ongoing symptoms in the subacute or chronic
      setting. (c) RSNA, 2017.

PMID- 28514215
TI  - Risk Factors for Aneurysm Recurrence.

PMID- 28514217
TI  - In Memoriam.

PMID- 28514218
TI  - The Effect of Iodine-based Contrast Material on Radiation Dose at CT: It's
      Complicated.

PMID- 28514219
TI  - Science to Practice: Killing Dormant Cells-Is Targeting Autophagy the Key to
      Complete Tumor Response in Transarterial Chemoembolization?
AB  - In this issue of Radiology, Gade et al ( 1 ) describe a unique mechanism of
      hepatocellular carcinoma (HCC) cells for surviving ischemia induced by
      transarterial embolization (TAE)/transarterial chemoembolization (TACE) in a
      state of cell cycle arrest-a function that may serve as a defensive shield
      against conventional chemotherapeutic agents. This finding adds to our knowledge
      and establishes a previously poorly understood mechanism of chemoresistance in
      HCC. As the Achilles heel in terms of this process, a concurrent upregulation of
      autophagic flux as an adaptive response to TAE-like ischemia was found by the
      authors. This is a targetable mechanism that can potentially be exploited for
      combined therapeutic approaches of embolotherapy and autophagy inhibition in HCC.

PMID- 28514220
TI  - Case 242: Radiation-induced Angiosarcoma.
AB  - History In 2004, this woman received a diagnosis of invasive mammillary
      carcinoma, tubular variant, strongly positive for estrogen and progesterone
      receptors. Her lesion was found at screening mammography performed at an outside
      institution when she was 59 years old. She underwent partial mastectomy, with
      partial axillary node dissection and sentinel node mapping. A 0.6 * 0.5 cm
      Nottingham grade 1 infiltrating ductal carcinoma was removed from the right upper
      outer quadrant, margins were free of tumor, and there was no angiolymphatic
      invasion. The six dissected lymph nodes were negative for malignancy. Her
      surgical history was otherwise unremarkable. Her medical history was positive for
      hypercholesterolemia and depression. Pertinent family history included breast
      cancer in both her mother and her sister. Given the patient's age, tumor size,
      lack of nodal involvement, and clear surgical margins, she met recommended
      MammoSite criteria, and she underwent accelerated partial breast radiation. She
      subsequently received 340 cGy of radiation twice a day for a total dose of 3400
      cGy in 10 administrations in February 2005. Accelerated partial breast radiation
      treatment was completed in February 2005, and she received subsequent routine
      care. Prior to 2014, the only postoperative complication was a chronic radiation
      bed seroma, which required periodic percutaneous drainage. She did not develop
      postsurgical lymphedema. In December 2013, 9 years after accelerated partial
      breast radiation treatment, she experienced progressive painful pruritic breast
      fullness, skin dimpling, and skin discoloration of the mastectomy scar and
      radiation bed. She sought medical care in January 2014 after she noticed a
      periareolar ulcerating skin plaque, more noticeable nipple retraction, and new
      onset of retroareolar aching. At physical examination ( Fig 1 ), there was
      generalized periareolar erythema, dimpling, firmness, and fixation involving the
      central breast and right upper outer quadrant. There was more conspicuous
      retraction of the nipple when compared with that seen at prior examinations.
      Nipple discharge was not present. There was a 1-cm periareolar ulcerating skin
      plaque. The only discrete palpable finding was lumpectomy bed seroma. There was
      no palpable axillary adenopathy. [Figure: see text] A diagnostic mammogram was
      obtained and compared with the most recent studies available. Ultrasonography
      (US) and magnetic resonance (MR) imaging were performed. Her most recent
      mammogram, obtained 3 months earlier in September 2013, reported Breast Imaging
      Reporting and Data System (BI-RADS) category 2 findings (ie, stable postoperative
      benign findings).

PMID- 28514221
TI  - Tracking Eye Movements during CT Interpretation: Inferences of Reader Performance
      and Clinical Competency Require Clinically Realistic Procedures for Unconstrained
      Search.

PMID- 28514222
TI  - Optimum Management of Pulmonary Nodules.

PMID- 28514223
TI  - Hematogenous Osteomyelitis in Infants and Children: Imaging of a Changing
      Disease.
AB  - In children, hematogenous osteomyelitis is an infection that primarily affects
      the most vascularized regions of the growing skeleton. The disease has increased
      in frequency, virulence, and degree of soft-tissue involvement. The change in
      clinical manifestations and management over the past 2 decades should be
      reflected in the current imaging approach to the disease. Imaging of infection
      must depict the location of a single focus or of multiple foci of involvement and
      the presence of drainable collections. This review provides an overview of the
      imaging implications directed by the changing epidemiology, the newer insights of
      anatomy and pathophysiology, the imaging characteristics with emphasis on
      specific locations and disease complications, and the differential diagnosis
      considerations. In addition, basic imaging guidelines for appropriate extent of
      area to image based on patient age are provided. (c) RSNA, 2017.

PMID- 28514224
TI  - Case 246.

PMID- 28514225
TI  - Vector and Serologic Survey for Crimean-Congo Hemorrhagic Fever Virus in Poland.
AB  - In contrast to animals, Crimean-Congo hemorrhagic fever (CCHF) causes a severe
      disease in humans with a high mortality rate. The etiological agent, CCHF virus
      (CCHFV), can be transmitted by argasid and ixodid ticks, but arachnids of the
      genus Hyalomma, followed by Rhipicephalus and Dermacentor serve as the major
      vectors of this virus. The goal of the study was to assess the epidemiological
      situation of CCHFV infection in cattle in south-east Poland, and survey for
      potential tick vector species. A total of 592 bovine blood samples from animals
      located in the southernmost region in Poland were tested by IgG sandwich enzyme
      linked immunosorbent assay. Ticks (n = 993) from south-east Poland were collected
      from dogs, cats, cattle, and horses and tested by RT-PCR. All 592 serum samples
      were negative for IgG antibodies to CCHFV. Of the ticks collected, 125 were
      Dermacentor reticulatus and 868 represented Ixodes ricinus, both species are
      regarded as potential vectors of CCHFV. All tick samples were negative for the
      presence of CCHFV. Considering the zoonotic nature, public health importance, and
      the virus increasing spread, it was prudent to assess the seroprevalence of CCHFV
      in the south-east area of Poland, bordering with CCHFV endemic areas. It seems
      unlikely that CCHFV infection will suddenly spread in Poland, but considering the
      multiple possibilities of the virus introduction, serosurveys and vector
      biosurveillance should be conducted at regular intervals.

PMID- 28514226
TI  - The March of Science - The True Story.

PMID- 28514227
TI  - Real-Time Evolution of Zika Virus Disease Outbreak, Roatan, Honduras.
AB  - A Zika virus disease outbreak occurred in Roatan, Honduras, during September 2015
      July 2016. Blood samples and clinical information were obtained from 183 patients
      given a clinical diagnosis of suspected dengue virus infection. A total of 79
      patients were positive for Zika virus, 13 for chikungunya virus, and 6 for dengue
      virus.

PMID- 28514228
TI  - Outcomes for 2 Children after Peripartum Acquisition of Zika Virus Infection,
      French Polynesia, 2013-2014.
AB  - Congenital Zika virus infection is associated with severe brain anomalies and
      impaired function. To determine outcomes, we followed 2 affected children for ~30
      months. For 1 who was symptomatic at birth, transient hepatitis developed.
      However, neurodevelopment for both children was age appropriate.

PMID- 28514229
TI  - An open source, wireless capable miniature microscope system.
AB  - OBJECTIVE: Fluorescence imaging through head-mounted microscopes in freely
      behaving animals is becoming a standard method to study neural circuit function.
      Flexible, open-source designs are needed to spur evolution of the method.
      APPROACH: We describe a miniature microscope for single-photon fluorescence
      imaging in freely behaving animals. The device is made from 3D printed parts and
      off-the-shelf components. These microscopes weigh less than 1.8 g, can be
      configured to image a variety of fluorophores, and can be used wirelessly or in
      conjunction with active commutators. Microscope control software, based in Swift
      for macOS, provides low-latency image processing capabilities for closed-loop, or
      BMI, experiments. MAIN RESULTS: Miniature microscopes were deployed in the
      songbird premotor region HVC (used as a proper name), in singing zebra finches.
      Individual neurons yield temporally precise patterns of calcium activity that are
      consistent over repeated renditions of song. Several cells were tracked over
      timescales of weeks and months, providing an opportunity to study learning
      related changes in HVC. SIGNIFICANCE: 3D printed miniature microscopes, composed
      completely of consumer grade components, are a cost-effective, modular option for
      head-mounting imaging. These easily constructed and customizable tools provide
      access to cell-type specific neural ensembles over timescales of weeks.

PMID- 28514230
TI  - Causes of Death of Residents in ACGME-Accredited Programs 2000 Through 2014:
      Implications for the Learning Environment.
AB  - PURPOSE: To systematically study the number of U.S. resident deaths from all
      causes, including suicide. METHOD: The more than 9,900 programs accredited by the
      Accreditation Council for Graduate Medical Education (ACGME) annually report the
      status of residents. The authors aggregated ACGME data on 381,614 residents in
      training during years 2000 through 2014. Names of residents reported as deceased
      were submitted to the National Death Index to learn causes of death. Person-year
      calculations were used to establish resident death rates and compare them with
      those in the general population. RESULTS: Between 2000 and 2014, 324 individuals
      (220 men, 104 women) died while in residency. The leading cause of death was
      neoplastic disease, followed by suicide, accidents, and other diseases. For male
      residents the leading cause was suicide, and for female residents, malignancies.
      Resident death rates were lower than in the age- and gender-matched general
      population. Temporal patterns showed higher rates of death early in residency.
      Deaths by suicide were higher early in training, and during the first and third
      quarters of the academic year. There was no upward or downward trend in resident
      deaths over the 15 years of this study. CONCLUSIONS: Neoplastic disease and
      suicide were the leading causes of death in residents. Data for death by suicide
      suggest added risk early in residency and during certain months of the academic
      year. Providing trainees with a supportive environment and with medical and
      mental health services is integral to reducing preventable deaths and fostering a
      healthy physician workforce.

PMID- 28514231
TI  - Preoperative Pain Neuroscience Education Combined With Knee Joint Mobilization
      for Knee Osteoarthritis: A Randomized Controlled Trial.
AB  - OBJECTIVES: This study aimed to first compare the effects of a preoperative
      treatment combining pain neuroscience education (PNE) with knee joint
      mobilization versus biomedical education with knee joint mobilization on central
      sensitization (CS) in patients with knee osteoarthritis, both before and after
      surgery. Second, we wanted to compare the effects of both interventions on knee
      pain, disability, and psychosocial variables. MATERIALS AND METHODS: Forty-four
      patients with knee osteoarthritis were allocated to receive 4 sessions of either
      PNE combined with knee joint mobilization or biomedical education with knee joint
      mobilization before surgery. All participants completed self-administered
      questionnaires and quantitative sensory testing was performed at baseline, after
      treatment and at a 1 month follow-up (all before surgery), and at 3 months after
      surgery. RESULTS: Significant and clinically relevant differences before and
      after surgery were found after treatments for both knee pain and disability, and
      some measures of CS (ie, widespread hyperalgesia, CS inventory), with no
      significant between-group differences. Other indicators of CS (ie, conditioned
      pain modulation, temporal summation) did not change over time following either
      treatment, and in some occasions the observed changes were not in the expected
      direction. Patients receiving PNE with knee joint mobilization achieved greater
      improvements in psychosocial variables (pain catastrophizing, kinesiophobia) both
      before and after surgery. DISCUSSION: Preoperative PNE combined with knee joint
      mobilization did not produce any additional benefits over time for knee pain and
      disability, and CS measures compared with biomedical education with knee joint
      mobilization. Superior effects in the PNE with knee joint mobilization group were
      only observed for psychosocial variables related to pain catastrophizing and
      kinesiophobia.

PMID- 28514233
TI  - Energy Balance over One Athletic Season.
AB  - INTRODUCTION: Magnitude and variation in energy balance (EB) components over an
      athletic season are largely unknown. PURPOSE: We investigated the longitudinal
      changes in EB over one season and explored the association between EB variation
      and change in the main fat-free mass (FFM) components in highly trained athletes.
      METHODS: Eighty athletes (54 males; handball, volleyball, basketball, triathlete,
      and swimming) were evaluated from the beginning of the season to the main
      competition stage. Resting and total energy expenditure (REE and TEE,
      respectively) were assessed by indirect calorimetry and doubly labeled water,
      respectively. Physical activity energy expenditure was calculated as TEE - 0.1
      TEE - REE. Fat mass (FM), FFM, and bone mineral were evaluated with dual-energy x
      ray absorptiometry; changed body energy stores were calculated as
      1.0(DeltaFFM/Deltatime) + 9.5(DeltaFM/Deltatime). Total-body water (TBW) and its
      compartments were assessed through dilution techniques, and total-body protein
      was calculated from a four-compartment model, with body volume assessed by air
      displacement plethysmography. RESULTS: Although a negative EB of -17.4 +/- 72.7
      kcal.d was observed (P < 0.05), EB varied widely among sports and across sex
      groups resulting in a net weight increase (0.7 +/- 2.3 kg) that is attributable
      to significant changes in FFM (1.2 +/- 1.6 kg) and FM (-0.7 +/- 1.5 kg) (P <
      0.05). EB was related with TBW and intracellular water (r = 0.354, r = 0.257, P <
      0.05, respectively), regardless of sex, sports, and age. CONCLUSIONS: The mean
      negative EB observed over the season resulted from the rate of FM use and FFM
      accretion, but with a large variation by sex and sports. TBW, but not total-body
      protein or mineral balance, explained the magnitude of EB, which means that
      athletes under a positive or a negative EB showed a TBW expansion or shrinkage,
      respectively, specifically within the cells, over one athletic season.

PMID- 28514232
TI  - PPARgamma Agonists Attenuate Trigeminal Neuropathic Pain.
AB  - OBJECTIVES: The aim of this study is to investigate the role of peroxisome
      proliferator-activated receptor-gamma isoform (PPARgamma), in trigeminal
      neuropathic pain utilizing a novel mouse trigeminal inflammatory compression
      (TIC) injury model. RESULTS: The study determined that the PPARgamma nuclear
      receptor plays a significant role in trigeminal nociception transmission,
      evidenced by: 1) Intense PPARgamma immunoreactivity is expressed 3 weeks after
      TIC nerve injury in the spinal trigeminal caudalis, the termination site of
      trigeminal nociceptive nerve fibers. 2) Systemic administration of a PPARgamma
      agonist, pioglitazone (PIO), attenuates whisker pad mechanical allodynia at doses
      of 300 mg/kg i.p. and 600 mg/kg p.o. 3) Administration of a PPARgamma antagonist,
      GW9662 (30 mg/kg i.p.), prior to providing the optimal dose of PIO (300 mg/kg
      i.p.) blocked the analgesic effect of PIO. DISCUSSION: This is the first study
      localizing PPARgamma immunoreactivity throughout the brainstem trigeminal sensory
      spinal nucleus (spV) and its increase three weeks after TIC nerve injury. This is
      also the first study to demonstrate that activation of PPARgamma attenuates
      trigeminal hypersensitivity in the mouse TIC nerve injury model. The findings
      presented here suggest the possibility of utilizing the FDA approved diabetic
      treatment drug, PIO, as a new therapeutic that targets PPARgamma for treatment of
      patients suffering from orofacial neuropathic pain.

PMID- 28514234
TI  - Associations Between Physical Pain, Pain Management, and Frequency of Nonmedical
      Prescription Opioid Use Among Young Adults: A Sex-specific Analysis.
AB  - OBJECTIVES: We sought to determine sex-specific associations between experiences
      of physical pain, pain management, and frequency of nonmedical prescription
      opioid (NMPO) use among young adults. METHODS: Among participants enrolled in the
      Rhode Island Young Adult Prescription Drug Study, we identified associations
      between physical pain in the past 6 months, pain history, pain management,
      polysubstance use, and weekly NMPO use. In sex-specific models, independent
      correlates of weekly NMPO use were identified via modified stepwise Poisson
      regression. RESULTS: Of 199 participants, the mean age was 24.6, and 65.3% were
      male. The racial composition was 16.6% black, 60.8% white, and 22.1% mixed or
      other race. A total of 119 (59.8%) participants reported weekly or greater NMPO
      use. The majority of male (86.2%) and female (84.1%) participants reported ever
      experiencing severe pain. A majority of males (72.3%) and females (81.2%)
      reported that they engaged in NMPO use to treat their physical pain, and one
      quarter (26.9%) of males and one-third (36.2%) of females had been denied a
      prescription from a doctor to treat severe pain. Among males, frequent NMPO use
      was independently associated with white race (P < 0.001) and reporting greater
      physical pain (P = 0.002). Among females, older age (P = 0.002) and monthly or
      greater nonmedical benzodiazepine use (P = 0.001) were independently associated
      with weekly NMPO use. CONCLUSIONS: Among young men in Rhode Island, physical pain
      may be related to frequent NMPO use. More research is needed to identify sex
      specific, pain-related factors that are linked with NMPO use to improve harm
      reduction and pain management interventions.

PMID- 28514236
TI  - A Kinked Epidural Needle Tip Preventing Placement of an Epidural Catheter.

PMID- 28514235
TI  - Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on
      Chronic Opioid Therapy.
AB  - OBJECTIVES: Individuals taking opioids for an extended period of time may become
      physically dependent, and will therefore experience opioid withdrawal should they
      stop taking the medication. Previous work in animal and human models has shown
      that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In
      this study, we investigated if ondansetron, a 5-HT3-receptor antagonist, could
      reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans.
      METHODS: In this double-blinded, randomized, crossover study, 33 chronic back
      pain patients (N = 33) were titrated onto sustained-release oral morphine for 30
      days. After titration, participants attended 2 study sessions, 1 week apart, in
      which opioid withdrawal was induced with intravenous naloxone, with or without 8
      mg intravenous ondansetron pretreatment. Opioid withdrawal symptoms were assessed
      by a blinded research assistant (objective opioid withdrawal score [OOWS]) and by
      the research participant (subjective opioid withdrawal score [SOWS]). RESULTS:
      Clinically significant signs of withdrawal were observed during both the
      ondansetron (DeltaOOWS = 3.58 +/- 2.22, P < 0.0001; DeltaSOWS = 12.48 +/- 11.18,
      P < 0.0001) and placebo sessions (DeltaOOWS = 3.55 +/- 2.39, P < 0.0001;
      DeltaSOWS = 12.21 +/- 10.72, P < 0.0001), but no significant differences were
      seen between the treatment sessions in either the OOWS or SOWS scores.
      CONCLUSION: We hypothesized that ondansetron would reduce opioid withdrawal
      symptoms in human subjects, but found no difference in withdrawal severity
      between ondansetron and placebo sessions. These findings suggest that more
      investigation may be necessary to determine if 5-HT3-receptor antagonists are
      suitable treatment options for opioid withdrawal.

PMID- 28514237
TI  - Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case
      Series.
AB  - PURPOSE: The aim of the study was to assess the effectiveness, tolerability, and
      safety of oral ketamine as an antidepressant treatment in adults with treatment
      resistant depression. METHODS: We reviewed retrospective data on 22 patients with
      treatment-resistant depression, who failed at least 3 adequate antidepressant
      treatment trials and 1 adequate trial of repetitive transcranial magnetic
      stimulation; subsequently, they received open-label treatment with oral ketamine,
      commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days,
      according to response and tolerability. The primary outcome measure was the Beck
      Depression Inventory II, which was used to rate subjective mood improvement at
      baseline and then at each follow-up visit. Data about adverse effects related to
      ketamine and a self-harm risk assessment were also obtained. FINDINGS: Over the
      course of treatment, 18% of the patients showed greater than 50% reduction in the
      Beck Depression Inventory II scores, 14% reported partial improvement in mood
      symptoms, while 45% had no response to ketamine and 23% showed a mild worsening
      in their depressive symptoms. The most frequent adverse effects were acute
      dissociation, dizziness, blurred vision, numbness and sedation. Neither serious
      adverse effects, nor any cases of abuse or dependence were observed. CONCLUSIONS:
      Although this case series found oral ketamine to be safe and well tolerated, the
      findings also showed rather modest effectiveness of oral ketamine in treatment
      resistant depression, with only approximately 30% reporting some benefit and
      approximately 70% reporting no change or worsening of mood. However, bearing in
      mind the limitations of this small, open-label case series, further exploration
      of the effectiveness of oral ketamine is warranted.

PMID- 28514238
TI  - The Influence of Maternal Pragmatics on the Language Skills of Children with
      Autism.
AB  - OBJECTIVE: This study examined the relationship between mothers' pragmatics and
      child language in autism spectrum disorder (ASD) and non-ASD language delay (LD)
      mother-child dyads. METHODS: Participants consisted of 20 dyads of mothers and
      their toddlers aged 24 to 48 months, with ASD (n = 10) or non-ASD LD (n = 10).
      Groups were matched on child chronological age, language, and cognition. Maternal
      pragmatic language was qualified based on the degree of pragmatic violations
      during a semistructured interview, and was examined in relation to both child
      language, as measured by the Preschool Language Scale-4 and maternal use of
      language facilitation strategies during play. RESULTS: Lower rates of maternal
      pragmatic violations were associated with higher expressive language scores in
      children with ASD, and with higher receptive language scores for children with
      non-ASD LD. Within ASD dyads, maternal pragmatic violations were negatively
      related to mothers' use of linguistic expansions. CONCLUSION: These findings
      indicate that parental pragmatics likely contribute to early language learning,
      and that the effects of maternal pragmatics on early language in ASD may be
      indirect (e.g., through parents' use of facilitative strategies). Parent-mediated
      language interventions for ASD should therefore consider parent pragmatics,
      especially given that pragmatic differences have been identified in unaffected
      family members of individuals with ASD.

PMID- 28514239
TI  - Understanding Women's Sexual Behaviors That May Put Them at Risk for Human
      Papillomavirus-Related Neoplasias: What Should We Ask?
AB  - OBJECTIVES: Human papillomavirus is a multifocal infection that can involve the
      cervix, vagina, vulva, anus, and oropharynx. Our study aimed to determine whether
      standard sexual history questions regarding anal intercourse identify women
      participating in anal-related sexual practices. MATERIALS AND METHODS: A cross
      sectional survey was conducted at the dysplasia clinic of a large academic
      medical center. Women presenting with human papillomavirus-related cervical,
      vulvar, or vaginal abnormalities were eligible. Participants completed a self
      administered sexual history questionnaire that included standard sexual history
      questions and more detailed questions about sexual practices. Additional
      demographic information was obtained from chart review. RESULTS: A total of 149
      eligible women were approached, 125 (84%) consented and enrolled (ages = 21-65
      years). Forty-seven (44%) reported participating in some type of anal-related
      sexual practice: anal fingering, oral-anal penetration, or anal intercourse. Of
      those participating in anal-related practices, 5 (11%) reported only anal
      fingering or oral-anal penetration. Thus, adding the new anal questions detected
      an additional 5% of women with high-risk anal behaviors that may have been missed
      by the standard question (p = .06). Seventy-nine women (63%) reported receiving
      oral penetration of the vagina, and 102 (82%) reported receiving vaginal
      fingering. Fifty-nine women (47%) used sex toys: 58 (98%) used sex toys
      vaginally, with 5 (8.5%) using them also anally. CONCLUSIONS: Women are willing
      to report their participation in a range of sexual practices. Of those who
      participated in anal practices, 11% did not have anal intercourse. Adding
      additional sexual health questions to clinical intake forms may enable clinicians
      to better counsel their patients on risky sexual behaviors.

PMID- 28514240
TI  - Raising the Alarm on Brain Attacks in Surgical Patients: Are We Doing Enough to
      Prevent and Treat Postoperative Strokes?

PMID- 28514241
TI  - Phrenic Nerve Palsy and Regional Anesthesia for Shoulder Surgery: Anatomical,
      Physiologic, and Clinical Considerations.
AB  - Regional anesthesia has an established role in providing perioperative analgesia
      for shoulder surgery. However, phrenic nerve palsy is a significant complication
      that potentially limits the use of regional anesthesia, particularly in high-risk
      patients. The authors describe the anatomical, physiologic, and clinical
      principles relevant to phrenic nerve palsy in this context. They also present a
      comprehensive review of the strategies for reducing phrenic nerve palsy and its
      clinical impact while ensuring adequate analgesia for shoulder surgery. The most
      important of these include limiting local anesthetic dose and injection volume
      and performing the injection further away from the C5-C6 nerve roots. Targeting
      peripheral nerves supplying the shoulder, such as the suprascapular and axillary
      nerves, may be an effective alternative to brachial plexus blockade in selected
      patients. The optimal regional anesthetic approach in shoulder surgery should be
      tailored to individual patients based on comorbidities, type of surgery, and the
      principles described in this article.

PMID- 28514242
TI  - Risks of Cardiovascular Adverse Events and Death in Patients with Previous Stroke
      Undergoing Emergency Noncardiac, Nonintracranial Surgery: The Importance of
      Operative Timing.
AB  - BACKGROUND: The outcomes of emergent noncardiac, nonintracranial surgery in
      patients with previous stroke remain unknown. METHODS: All emergency surgeries
      performed in Denmark (2005 to 2011) were analyzed according to time elapsed
      between previous ischemic stroke and surgery. The risks of 30-day mortality and
      major adverse cardiovascular events were estimated as odds ratios (ORs) and 95%
      CIs using adjusted logistic regression models in a priori defined groups
      (reference was no previous stroke). In patients undergoing surgery immediately
      (within 1 to 3 days) or early after stroke (within 4 to 14 days), propensity
      score matching was performed. RESULTS: Of 146,694 nonvascular surgeries
      (composing 98% of all emergency surgeries), 5.3% had previous stroke (mean age,
      75 yr [SD = 13]; 53% women, 50% major orthopedic surgery). Antithrombotic
      treatment and atrial fibrillation were more frequent and general anesthesia less
      frequent in patients with previous stroke (all P < 0.001). Risks of major adverse
      cardiovascular events and mortality were high for patients with stroke less than
      3 months (20.7 and 16.4% events; OR = 4.71 [95% CI, 4.18 to 5.32] and 1.65 [95%
      CI, 1.45 to 1.88]), and remained increased for stroke within 3 to 9 months (10.3
      and 12.3%; OR = 1.93 [95% CI, 1.55 to 2.40] and 1.20 [95% CI, 0.98 to 1.47]) and
      stroke more than 9 months (8.8 and 11.7%; OR = 1.62 [95% CI, 1.43 to 1.84] and
      1.20 [95% CI, 1.08 to 1.34]) compared with no previous stroke (2.3 and 4.8%
      events). Major adverse cardiovascular events were significantly lower in 323
      patients undergoing immediate surgery (21%) compared with 323 successfully
      propensity-matched early surgery patients (29%; P = 0.029). CONCLUSIONS: Adverse
      cardiovascular outcomes and mortality were greatly increased among patients with
      recent stroke. However, events were higher 4 to 14 days after stroke compared
      with 1 to 3 days after stroke.

PMID- 28514243
TI  - Celiac Disease Symptom Resolution: Effectiveness of the Gluten-free Diet.
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of the gluten-free
      diet (GFD) on gastrointestinal (GI) and extra-intestinal (EI) symptom resolution
      and identify predictors for persistence of symptoms in all celiac patients at the
      University of Chicago. METHODS: We conducted a retrospective chart review from
      2002 to 2015. GI symptoms included abdominal pain, bloating, constipation,
      diarrhea, failure to thrive/weight loss, nausea, reflux, and vomiting. EI
      symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis
      herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgia,
      psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed
      puberty, osteoporosis, and infertility. RESULTS: A total of 554 patients (227
      children) with celiac disease (CeD) were included. Abdominal pain, diarrhea and
      failure to thrive were the most common GI symptoms in children whereas diarrhea,
      bloating, and abdominal pain were most common in adults. Short stature, fatigue,
      and headache were the most common EI symptoms in children whereas iron deficiency
      anemia, fatigue, and headache/psychiatric disorders were most common in adults.
      Children had significantly higher rates of EI and GI symptom resolution as
      compared to adults, with greater rates of improvements in GI versus EI symptoms
      at more than 24 months. Long duration of symptoms, female sex, and non-adherence
      to a GFD were the most important significant predictors of failure to clinically
      improve. CONCLUSIONS: On a strict GFD, children report greater rates of both GI
      and EI symptom resolution as compared to adults with greater rates of improvement
      in GI over EI symptoms. Early recognition of CeD and close attention to diet
      adherence may help in symptom resolution.

PMID- 28514245
TI  - Comparison of Ocular Lubricant Osmolalities.
AB  - PURPOSE: The aim of this study was to evaluate the osmolality of commercially
      available ocular tear lubricants. METHODS: Thirty-seven (n = 37) ocular
      lubricants, measured three times each, were evaluated for osmolality using a
      vapor pressure osmometer (Wescor VAPRO 5520). The osmometer was calibrated before
      each use, and the order of the lubricants was randomized. Ambient temperature and
      humidity were monitored for stability. RESULTS: Of the 37 ocular lubricants
      tested, 35 (94.6%) had an osmolality of less than 295 mmol/kg, one (2.7%) had
      between 295 and 308 mmol/kg, and one (2.7%) had more than 308 mmol/kg. The
      ambient room temperature was stable and ranged from 21.9 degrees C to 22.0
      degrees C, and the relative humidity ranged from 21.2% to 25.6% during
      experimentation. When ocular lubricants were grouped by ingredient
      (carboxymethylcellulose and hydroxylpropyl methylcellulose, hyaluronic acid, and
      hydroxypropyl guar), no significant difference in osmolality was noted between
      groups (Mann-Whitney U test, P > .05). CONCLUSIONS: The majority of the ocular
      lubricants tested had low osmolalities, mimicking the osmolarity of newly formed
      tears (295 to 300 mOsm/L). Several factors need to be considered when choosing a
      tear lubricant, which have more complex formulations than ever. Knowledge of
      their osmolality may be an added parameter to consider when choosing therapeutic
      options for dry eye.

PMID- 28514244
TI  - The Safety of Soft Contact Lenses in Children.
AB  - PURPOSE: There is increasing interest in fitting children with soft contact
      lenses. This review collates data from a range of studies to estimate the
      incidence of complications, specifically corneal infiltrative events and
      microbial keratitis, in patients under the age of 18 years. METHODS: Peer-review
      papers were identified using PubMed and the Web of Science. A broad range of
      studies are summarized including large-scale epidemiological studies of contact
      lens-related complications, hospital-based case series, long- and short-term
      prospective studies, and multicenter retrospective studies. RESULTS: Nine
      prospective studies representing 1800 patient years of wear in 7- to 19-year-olds
      include safety outcomes. In three large prospective studies representing between
      159 and 723 patient years of soft contact lens wear in patients 8 to 14 years,
      the incidence of corneal infiltrative events is up to 136 per 10,000 years. Data
      from a large retrospective study show similar rates of corneal infiltrative
      events: 97 per 10,000 years in 8- to 12-year-olds (based on 411 patient years of
      wear) and 335 per 10,000 years in 13- to 17-year-olds (based on 1372 patient
      years of wear). None of the prospective studies report any cases of microbial
      keratitis. Five clinical studies where safety data are not reported constitute a
      further 493 patient years. One retrospective study found no cases of microbial
      keratitis occurred in 8- to 12-year-olds (411 patient years) and an incidence of
      15 per 10,000 patient years in 13- to 17-year-olds (1372 patient years)-no higher
      than the incidence of microbial keratitis in adults wearing soft contact lenses
      on an overnight basis. CONCLUSIONS: The overall picture is that the incidence of
      corneal infiltrative events in children is no higher than in adults, and in the
      youngest age range of 8 to 11 years, it may be markedly lower.

PMID- 28514246
TI  - The Development of the Chinese Intermittent Exotropia Questionnaire.
AB  - PURPOSE: The Intermittent Exotropia Questionnaire (IXTQ) is a child, proxy, and
      parent report of health-related quality of life specific to children with
      intermittent exotropia (IXT). The present study aimed to develop a Chinese
      language version of the IXTQ (CIXTQ) and evaluate its validity and reliability
      when used in Chinese IXT children and their parents. METHODS: The IXTQ was
      translated into Chinese. One hundred seventy-five IXT children (2 to 17 years
      old) and 151 orthotropic control children (2 to 17 years old) along with one of
      their parents were recruited. Children 5 to 17 years old completed the 5- to 7
      year-old or the 8- to 17-year-old child questionnaire of the CIXTQ according to
      their age. Parents of all children (2 to 17 years old) completed the proxy and
      parent questionnaires of the CIXTQ. Psychometric properties of the CIXTQ were
      examined for floor and ceiling effects, construct validity, item-internal
      consistency, discriminative validity, Cronbach alpha coefficient and test-retest
      reliability. RESULTS: No items were found to have strong floor or ceiling
      effects. Principal component analysis identified that the CIXTQ had a similar
      structure to the original English version. The median scores of each
      questionnaire in the CIXTQ among children with IXT and their parents were
      significantly lower than those among control subjects (P < .001). Cronbach alpha
      coefficients ranged from 0.869 to 0.931, and test-retest reliabilities ranged
      from 0.898 to 0.981, for each questionnaire in the CIXTQ. CONCLUSIONS: The CIXTQ
      is a useful tool to evaluate the influence of IXT on health-related quality of
      life among Chinese IXT children and their parents.

PMID- 28514247
TI  - Corneal Equilibrium Flux as a Function of Corneal Surface Oxygen Tension.
AB  - PURPOSE: Oxygen is essential for aerobic mammalian cell physiology. Oxygen
      tension (PO2) should reach a minimum at some position within the corneal stroma,
      and oxygen flux should be zero, by definition, at this point as well. We found
      the locations and magnitudes of this "corneal equilibrium flux" (xmin) and
      explored its physiological implications. METHODS: We used an application of the
      Monod kinetic model to calculate xmin for normal human cornea as anterior surface
      PO2 changes from 155 to 20 mmHg. RESULTS: We find that xmin deepens, broadens,
      and advances from 1.25 MUm above the endothelial-aqueous humor surface toward the
      epithelium (reaching a position 320 MUm above the endothelial-aqueous humor
      surface) as anterior corneal surface PO2 decreases from 155 to 20 mmHg.
      CONCLUSIONS: Our model supports an anterior corneal oxygen flux of 9 MUL O2 . cm
      . h and an epithelial oxygen consumption of approximately 4 MUL O2 . cm . h. Only
      at the highest anterior corneal PO2 does our model predict that oxygen diffuses
      all the way through the cornea to perhaps reach the anterior chamber. Of most
      interest, corneal oxygen consumption should be supported down to a corneal
      surface PO2 of 60 to 80 mmHg but declines below this range. We conclude that the
      critical oxygen tension for hypoxia induced corneal swelling is more likely this
      range rather than a fixed value.

PMID- 28514248
TI  - Foveal Curvature and Asymmetry Assessed Using Optical Coherence Tomography.
AB  - PURPOSE: The aims of this study were to use cross-sectional optical coherence
      tomography imaging and custom curve fitting software to evaluate and model the
      foveal curvature as a spherical surface and to compare the radius of curvature in
      the horizontal and vertical meridians and test the sensitivity of this technique
      to anticipated meridional differences. METHODS: Six 30-degree foveal-centered
      radial optical coherence tomography cross-section scans were acquired in the
      right eye of 20 clinically normal subjects. Cross sections were manually
      segmented, and custom curve fitting software was used to determine foveal pit
      radius of curvature using the central 500, 1000, and 1500 MUm of the foveal
      contour. Radius of curvature was compared across different fitting distances.
      Root mean square error was used to determine goodness of fit. The radius of
      curvature was compared between the horizontal and vertical meridians for each
      fitting distance. RESULTS: There radius of curvature was significantly different
      when comparing each of the three fitting distances (P < .01 for each comparison).
      The average radii of curvature were 970 MUm (95% confidence interval [CI], 913 to
      1028 MUm), 1386 MUm (95% CI, 1339 to 1439 MUm), and 2121 MUm (95% CI, 2066 to
      2183) for the 500-, 1000-, and 1500-MUm fitting distances, respectively. Root
      mean square error was also significantly different when comparing each fitting
      distance (P < .01 for each comparison). The average root mean square errors were
      2.48 MUm (95% CI, 2.41 to 2.53 MUm), 6.22 MUm (95% CI, 5.77 to 6.60 MUm), and
      13.82 MUm (95% CI, 12.93 to 14.58 MUm) for the 500-, 1000-, and 1500-MUm fitting
      distances, respectively. The radius of curvature between the horizontal and
      vertical meridian radii was statistically different only in the 1000- and 1500
      MUm fitting distances (P < .01 for each), with the horizontal meridian being
      flatter than the vertical. CONCLUSIONS: The foveal contour can be modeled as a
      sphere with low curve fitting error over a limited distance and capable of
      detecting subtle foveal contour differences between meridians.

PMID- 28514249
TI  - Heart Transplantation From DCD donors: From the Bedside to the Bench.

PMID- 28514250
TI  - Accept or Decline? An Analytics-Based Decision Tool for Kidney Offer Evaluation.
AB  - BACKGROUND: When a deceased-donor kidney is offered to a waitlisted candidate,
      the decision to accept or decline the organ relies primarily upon a
      practitioner's experience and intuition. Such decisions must achieve a delicate
      balance between estimating the immediate benefit of transplantation and the
      potential for future higher-quality offers. However, the current experience-based
      paradigm lacks scientific rigor and is subject to the inaccuracies that plague
      anecdotal decision-making. METHODS: A data-driven analytics-based model was
      developed to predict whether a patient will receive an offer for a deceased-donor
      kidney at Kidney Donor Profile Index thresholds of 0.2, 0.4, and 0.6, and at
      timeframes of 3, 6, and 12 months. The model accounted for Organ Procurement
      Organization, blood group, wait time, DR antigens, and prior offer history to
      provide accurate and personalized predictions. Performance was evaluated on data
      sets spanning various lengths of time to understand the adaptability of the
      method. RESULTS: Using United Network for Organ Sharing match-run data from March
      2007 to June 2013, out-of-sample area under the receiver operating characteristic
      curve was approximately 0.87 for all Kidney Donor Profile Index thresholds and
      timeframes considered for the 10 most populous Organ Procurement Organizations.
      As more data becomes available, area under the receiver operating characteristic
      curve values increase and subsequently level off. CONCLUSIONS: The development of
      a data-driven analytics-based model may assist transplant practitioners and
      candidates during the complex decision of whether to accept or forgo a current
      kidney offer in anticipation of a future high-quality offer. The latter holds
      promise to facilitate timely transplantation and optimize the efficiency of
      allocation.

PMID- 28514252
TI  - Mechanisms of distraction in acute pain perception and modulation.

PMID- 28514251
TI  - Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience.
AB  - OBJECTIVE: A principal aim of the Adult-to-Adult Living Donor Liver
      Transplantation Cohort Study was to study hepatic blood flow and effect of portal
      flow modulation on graft outcomes in the setting of increasing use of smaller and
      left lobe grafts. METHODS: Recipients of 274 living donor liver transplant were
      enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study,
      including 233 (85.0%) right lobes, 40 (14.6%) left lobes, and 1 (0.5%) left
      lateral section. Hepatic hemodynamics were recorded after reperfusion. A total of
      57 portal flow modulations were performed on 52 subjects. RESULTS: Modulation
      lowered portal pressure in 68% of subjects with inconsistent effects on hepatic
      arterial and portal flow. A higher rate of graft dysfunction was observed in
      modulated vs. unmodulated subjects (31% vs. 18%; P = 0.03); however, graft
      survival in modulated subjects was not different from unmodulated subjects at 3
      years. CONCLUSIONS: These results suggest the need for a study using a
      prespecified portal flow modulation protocol with defined indications to better
      define the effects of these interventions.

PMID- 28514253
TI  - Widespread effects of clinically unilateral focal nerve injuries.

PMID- 28514254
TI  - Reply.

PMID- 28514255
TI  - A conceptual framework for "updating the definition of pain".

PMID- 28514256
TI  - Reply.

PMID- 28514257
TI  - The effect of nothing? Time to abandon the concept of placebo.

PMID- 28514258
TI  - Reply.

PMID- 28514259
TI  - Does Type 1 Diabetes Mellitus Affect the Shear Wave Velocity of the Thyroid Gland
      of Children Without Autoimmune Thyroiditis?
AB  - OBJECTIVE: The aim of this study is to evaluate the shear wave velocity (SWV) of
      the thyroid gland with acoustic radiation force impulse elastography in children
      with type 1 diabetes mellitus (T1D). MATERIALS AND METHODS: Between November 2015
      and April 2016, 35 T1D patients who were referred to our hospital's endocrinology
      outpatient clinic (mean age, 11.88 +/- 4.1 years) and 30 children (mean age, 11.3
      +/- 3.08 years) in the control group were enrolled in the study. Five acoustic
      radiation force impulse elastography measurements from each lobe of the thyroid
      gland in m/s were recorded. Diabetes age, hemoglobin A1c, and C-peptide levels
      were recorded in T1D patients. Statistical analyses were performed using SPSS
      version 21 (IBM Corporation, Armonk, NY). RESULTS: The mean SWV of the thyroid
      gland in T1D patients and the control group was 1.11 +/- 0.21 and 1.29 +/- 0.23
      m/s, respectively. The mean SWV of the thyroid gland in T1D patients was lower
      than that in the control group and this was significant (P = 0.002). The mean SWV
      of the thyroid gland was not correlated with hemoglobin A1c level, body mass
      index, or the insulin dose in T1D patients. CONCLUSIONS: The present study showed
      that T1D affects the thyroid gland stiffness even in patients without autoimmune
      thyroiditis. Acoustic radiation force impulse elastography may be a useful method
      in determining early changes in thyroid gland in T1D and may be used as a
      screening tool.

PMID- 28514260
TI  - Differential Diagnostic Value of Obstructive and Nonobstructive Azoospermia by
      Scrotal Ultrasound.
AB  - Our objective was to assess the differential diagnostic value of classification
      of obstructive versus nonobstructive azoospermia by scrotal ultrasound. Forty
      patients with azoospermia were selected for our study (ages, 23-35; average, 29
      +/- 5.34 years). Patients were divided into the obstructive (17) or
      nonobstructive (23) azoospermia category. Twenty "healthy" volunteers were
      selected for the control group. We observed the testis, epididymis, and vas
      deferens in all subjects. Testicular volumes were calculated and compared with
      the control group for both obstructive and nonobstructive groups. Cystic or
      tubular dilation of the epididymis was found in all patients with obstructive
      azoospermia. The patients with nonobstructive azoospermia had no significant
      abnormalities of the epididymis. There was no difference in the testicular
      volumes between the patients with obstructive azoospermia and healthy controls (P
      > 0.05). However, the testicular volumes of patients with nonobstructive
      azoospermia were smaller than those of healthy volunteers (P < 0.05). It is
      helpful to identify obstructive and nonobstructive azoospermia by scrotal
      ultrasound, because it is a less invasive method that can be used to isolate
      probable treatment options.

PMID- 28514261
TI  - Doppler Ultrasound Evaluation of Circulatory Support Devices.
AB  - In the setting of mechanical circulatory support devices, including ventricular
      assist devices, extracorporeal membrane oxygenation, intraaortic balloon pumps,
      and the total artificial heart, the spectral Doppler waveform is significantly
      altered, reflecting systemic hemodynamic changes. As the prevalence of these
      devices increases, a better understanding of both the devices themselves and
      their associated Doppler ultrasound findings is necessary for accurate image
      interpretation. This article reviews the clinical indications, pathophysiology,
      and sonographic findings of these devices, with emphasis on the variation in
      arterial Doppler waveforms that can be seen with normal function, as well as the
      major complications.

PMID- 28514262
TI  - Infection Control in Pediatric Spinal Deformity Surgery: A Systematic and
      Critical Analysis Review.

PMID- 28514263
TI  - Ventricular Energetics in Pediatric Left Ventricular Assist Device Patients: A
      Retrospective Clinical Study.
AB  - The aim of this study is to estimate the trend of right and left energetic
      parameters in left ventricular assist device (LVAD) pediatric patients.
      Echocardiographic data were retrospectively collected at the baseline, in the
      acute phase after and at the monthly follow-ups till the LVAD explantation to
      estimate left and right ventricular energetic parameters. A significant
      relationship between the left and right ventricular energetic parameter trends
      was found along all the study period. Left ventricular end-systolic pressure
      volume relationship improved till the follow-up of 2 months and then
      progressively decreases. Left arteroventricular coupling decreases after the
      LVAD, and right arteroventricular coupling decreases at the short-term follow-up.
      Left ventricular external work, potential energy, and pressure-volume area
      decrease at the short-term follow-up and then increase progressively. Right
      ventricular external work, potential energy, and pressure-volume area increase
      after the LVAD implantation. Left (right) cardiac mechanical efficiency is
      improved (worsened) by the LVAD. Energetic variables show that the LVAD benefits
      could decrease over time. A continuous and patient tailored LVAD setting could
      contribute to prolong LVAD benefits. The introduction of energetic parameters
      could lead to a more complete evaluation of LVAD patients' outcome which is a
      multiparametric process.

PMID- 28514264
TI  - Breaks in Sitting Time: Effects on Continuously Monitored Glucose and Blood
      Pressure.
AB  - PURPOSE: We examined the effects of interrupting prolonged sitting with multiple
      2-min walking breaks or one 30-min continuous walking session on glucose control
      and ambulatory blood pressure (ABP). METHODS: Ten overweight/obese, physically
      inactive participants (five men; 32 +/- 5 yr; BMI, 30.3 +/- 4.6 kg.m)
      participated in this randomized four-trial crossover study, with each trial
      performed on a separate, simulated workday lasting 9 h: 1) 30 min of continuous
      moderate-intensity (30-min MOD) walking at 71% +/- 4% HRmax; 2) 21 * 2 min bouts
      of moderate-intensity (2-min MOD) walking at 53% +/- 5% HRmax, each performed
      every 20 min (42 min total); 3) 8 * 2 min bouts of vigorous-intensity (2-min VIG)
      walking at 79% +/- 4% HRmax, each performed every hour (16 min total); 4) 9 h of
      prolonged sitting (SIT). Participants underwent continuous interstitial glucose
      monitoring and ABP monitoring during and after the simulated workday spent in the
      laboratory, with primary data analysis from 12:30 h to 07:00 h the next morning.
      RESULTS: Compared with SIT (5.6 +/- 1.1 mmol.L), mean 18.7-h glucose was lower
      during the 2-min MOD (5.2 +/- 1.1 mmol.L) and 2-min VIG (5.4 +/- 0.9 mmol.L)
      trials and mean 18.7-h glucose during the 30-min MOD trial (5.1 +/- 0.8 mmol.L)
      was lower than all other trials (P < 0.001). Postprandial glucose was
      approximately 7% to 13% lower during all trials compared with SIT (P < 0.001),
      with 30-min MOD having the greatest effect. Only the 30-min MOD trial was
      effective in reducing systolic ABP from 12:30 to 07:00 h (119 +/- 15 mm Hg) when
      compared with SIT (122 +/- 16 mm Hg; P < 0.05). CONCLUSIONS: Replacing sitting
      with 2-min MOD walking every 20 min or 2 min of vigorous-intensity walking every
      hour during a simulated workday reduced 18.7 h and postprandial glucose, but only
      30-min MOD walking was effective for reducing both glucose and systolic ABP.

PMID- 28514268
TI  - Primary care perspectives in autosomal dominant polycystic kidney disease.

PMID- 28514265
TI  - Television Viewing Time and Inflammatory-Related Mortality.
AB  - PURPOSE: Television (TV) viewing time is associated with increased risk of all
      cause, cardiovascular and cancer mortality. Although TV time is detrimentally
      associated with key inflammatory markers, the associations of TV time with other
      inflammatory-related mortality (with a predominant inflammatory, oxidative or
      infectious component, but not attributable to cancer or cardiovascular causes),
      are unknown. METHODS: Among 8933 Australian adults (4593 never-smokers) from the
      baseline (1999-2000) Australian Diabetes, Obesity and Lifestyle Study (median
      follow-up, 13.6 yr), we examined TV time in relation to noninflammatory and
      inflammatory-related mortality (not attributable to cancer or cardiovascular
      causes, hereafter "inflammatory-related" mortality). Because smoking has a
      significant inflammatory component, we also examined this relationship in never
      smokers. RESULTS: Of 896 deaths, 248 were attributable to cardiovascular disease,
      346 to cancer, 130 to other inflammatory-related causes (71 for never-smokers),
      and 172 to noninflammatory-related causes (87 for never-smokers). After
      multivariate adjustment for age, sex, education, household income, smoking
      status, alcohol intake, energy intake, diet, and cardiometabolic risk biomarkers
      (model 3), every additional hours per day of TV time was associated with
      increased risk of inflammatory-related mortality in the overall population
      (hazard ratio, 1.12; 95% confidence interval, 1.00-1.25) and in never-smokers
      (1.18; 1.00, 1.40). These results were attenuated after additional adjustment for
      leisure-time physical activity. After multivariate adjustment (model 3), no
      association was observed for noninflammatory mortality in the overall population
      (0.95; 0.85, 1.07), but risk tended to decrease for never-smokers (0.85; 0.75,
      1.02). CONCLUSIONS: In summary, before adjustment for leisure-time physical
      activity, TV time was associated with increased risk of inflammatory-related
      mortality. This is consistent with the hypothesis that high TV viewing may be
      associated with a chronic inflammatory state.

PMID- 28514269
TI  - Ensuring compliance with the HIPAA Security Rule: Think twice when e-mailing
      protected health information.

PMID- 28514270
TI  - Recognizing type 1 diabetes mellitus in children & adolescents.

PMID- 28514271
TI  - Managing herpes zoster in older adults: Prescribing considerations.

PMID- 28514272
TI  - Identifying delirium in older adults with pre-existing mental illness.
AB  - Acute delirium complicates care and can be easily overlooked in older adults with
      preexisting mental illness. Evidence-based measures have demonstrated that early
      diagnosis, identification, and correction of modifiable factors can lead to
      improved care and less morbidity in these patients.

PMID- 28514273
TI  - Bronchopulmonary sequestration: Improving practice by evaluating for a missed
      diagnosis.
AB  - Bronchopulmonary sequestration (BPS) is a lung mass that does not communicate
      with the tracheobronchial tree or the pulmonary arterial vasculature, and thus
      does not play a role in oxygenation. This article discusses the etiology of BPS,
      as well as its pathophysiology, signs and symptoms, imaging studies used to
      diagnose, and treatment options in both pediatric and adult patients.

PMID- 28514275
TI  - Acute exacerbation of COPD: Diagnosis and management.

PMID- 28514276
TI  - Sexual network drivers of HIV and herpes simplex virus type 2 transmission.
AB  - OBJECTIVES: HIV and herpes simplex virus type 2 (HSV-2) infections are sexually
      transmitted and propagate in sexual networks. Using mathematical modeling, we
      aimed to quantify effects of key network statistics on infection transmission,
      and extent to which HSV-2 prevalence can be a proxy of HIV prevalence.
      DESIGN/METHODS: An individual-based simulation model was constructed to describe
      sex partnering and infection transmission, and was parameterized with
      representative natural history, transmission, and sexual behavior data.
      Correlations were assessed on model outcomes (HIV/HSV-2 prevalences) and multiple
      linear regressions were conducted to estimate adjusted associations and effect
      sizes. RESULTS: HIV prevalence was one-third or less of HSV-2 prevalence. HIV and
      HSV-2 prevalences were associated with a Spearman's rank correlation coefficient
      of 0.64 (95% confidence interval: 0.58-0.69). Collinearities among network
      statistics were detected, most notably between concurrency versus mean and
      variance of number of partners. Controlling for confounding, unmarried
      mean/variance of number of partners (or alternatively concurrency) were the
      strongest predictors of HIV prevalence. Meanwhile, unmarried/married
      mean/variance of number of partners (or alternatively concurrency), and
      clustering coefficient were the strongest predictors of HSV-2 prevalence. HSV-2
      prevalence was a strong predictor of HIV prevalence by proxying effects of
      network statistics. CONCLUSION: Network statistics produced similar and
      differential effects on HIV/HSV-2 transmission, and explained most of the
      variation in HIV and HSV-2 prevalences. HIV prevalence reflected primarily mean
      and variance of number of partners, but HSV-2 prevalence was affected by a range
      of network statistics. HSV-2 prevalence (as a proxy) can forecast a population's
      HIV epidemic potential, thereby informing interventions.

PMID- 28514277
TI  - A commitment contract to achieve virologic suppression in poorly adherent
      patients with HIV/AIDS.
AB  - OBJECTIVE: Assess whether a commitment contract informed by behavioral economics
      leads to persistent virologic suppression among HIV-positive patients with poor
      antiretroviral therapy (ART) adherence. DESIGN: Single-center pilot randomized
      clinical trial and a nonrandomized control group. SETTING: Publicly funded HIV
      clinic in Atlanta, Georgia, USA. INTERVENTION: The study involved three arms.
      First, participants in the provider visit incentive (PVI) arm received $30 after
      attending each scheduled provider visit. Second, participants in the incentive
      choice arm were given a choice between the above arrangement and a commitment
      contract that made the $30 payment conditional on both attending the provider
      visit and meeting an ART adherence threshold. Third, the passive control arm
      received routine care and no incentives. PARTICIPANTS: A total of 110 HIV
      infected adults with a recent plasma HIV-1 viral load more than 200 copies/ml
      despite ART. The sample sizes of the three groups were as follows: PVI, n = 21;
      incentive choice, n = 19; and passive control, n = 70. MAIN OUTCOME MEASURE:
      Virologic suppression (plasma HIV-1 viral load <=200 copies/ml) at the end of the
      incentive period and at an unanticipated postincentive study visit approximately
      3 months later. RESULTS: The odds of suppression were higher in the incentive
      choice arm than in the passive control arm at the postincentive visit (adjusted
      odds ratio 3.93, 95% confidence interval 1.19-13.04, P = 0.025). The differences
      relative to the passive control arm at the end of the incentive period and
      relative to the PVI arm at both points in time were not statistically
      significant. CONCLUSION: Commitment contracts can improve ART adherence and
      virologic suppression. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT01455740.

PMID- 28514282
TI  - Recent progress in anti-HIV broadly neutralizing antibody research.

PMID- 28514281
TI  - Acute hyperinsulinemia effects on systemic markers of immune activation in HIV.
AB  - : The well treated HIV population remains at risk for insulin resistance and
      chronic immune activation. We tested the effects of acute hyperinsulinemia on
      inflammation in HIV. Twenty HIV-infected and 10 non-HIV-infected individuals well
      matched for BMI underwent oral glucose tolerance testing to stimulate insulin
      secretion and assess for changes in circulating soluble CD163, soluble CD14, and
      monocyte chemoattract protein 1. Soluble CD14 decreased significantly after
      stimulation of hyperinsulinemia and no significant changes in soluble CD163 or
      monocyte chemoattract protein 1 were demonstrated in HIV-infected and non-HIV
      infected groups.

PMID- 28514279
TI  - Impact of alemtuzumab on HIV persistence in an HIV-infected individual on
      antiretroviral therapy with Sezary syndrome.
AB  - OBJECTIVE: To study the effects of alemtuzumab on HIV persistence in an HIV
      infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare
      malignancy of CD4 T cells. DESIGN: Case report. METHODS: Blood was collected 30
      and 18 months prior to presentation with Sezary syndrome, at the time of
      presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR
      VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in
      total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was
      quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next
      generation sequencing. RESULTS: HIV-hepatitis B virus coinfection was diagnosed
      and antiretroviral therapy initiated 4 years prior to presentation with Sezary
      syndrome and primary cutaneous anaplastic large cell lymphoma. The patient
      received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post
      alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T
      cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length
      HIV-DNA sequencing demonstrated multiple defective viruses but no identical or
      expanded sequences. Alemtuzumab extensively depleted T cells, including more than
      1 log reduction in total T cells and more than 3 log reduction in CD4 T cells.
      Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained
      detectable at low levels even after depletion of nearly all CD4 T cells.
      CONCLUSION: Alemtuzumab extensively depleted multiple T-cell subsets and
      decreased the frequency of but did not eliminate HIV-infected CD4 T cells.
      Studying the effects on HIV persistence following immune recovery in HIV-infected
      individuals who require alemtuzumab for malignancy or in animal studies may
      provide further insights into novel cure strategies.

PMID- 28514283
TI  - Addressing the Public Health Epidemic of Firearm-related Violence in America.

PMID- 28514284
TI  - Comparison in anesthetic effects of propofol among patients with different ABO
      blood groups.
AB  - Our study was aimed to investigate anesthetic effects of propofol in patients
      with different blood groups.A total of 72 participants were enrolled from
      patients arranged for surgeries of cholecystectomy, tonsillectomy, and spinal
      operation. Each blood group (A, B, AB, and O) contained 18 participants. Mean
      arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were assayed
      with Philips monitor. These indexes were observed before propofol anesthesia
      (T0), and then were recorded when concentration of propofol was 1 MUg/mL (T1), 2
      MUg/mL (T2), 3 MUg/mL (T3), and 4 MUg/mL (T4). The differences in MAP, HR, and
      BIS at T0 among groups were compared with the chi test. Multiple comparisons were
      adopted to calculate the differences in MAP, HR, and BIS between groups at T1,
      T2, T3, and T4.No significant differences in age, sex, and weight of all groups
      were found (P > .05). Before propofol anesthesia (T0), all the participants
      exhibited no differences in MAP, HR, and BIS (P > .05). Subsequently, we found
      obvious differences in DeltaMAP, DeltaHR, and DeltaBIS between groups. The
      patients in the B blood group showed highest DeltaMAP and DeltaHR at each time
      point (P < .05 for both). As for DeltaBIS, patients in A blood group exhibited
      highest value at T3 and T4 (P < .05).The blood group remarkably affects the
      anesthetic effects of propofol.

PMID- 28514285
TI  - Association of ABCB1 C3435T polymorphism with the susceptibility to osteonecrosis
      of the femoral head: A meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The exploration for the etiology of osteonecrosis of
      the femoral head (ONFH) has got some promising findings, but the morbidity of
      ONFH is still not under control. The C3435T polymorphism of ATP-binding cassette
      subfamily B member 1 (ABCB1) gene has been reported to possess significant
      influence on ONFH onset, but relevant outcomes remain conflicting rather than
      conclusive. Therefore, a meta-analysis was useful to pool these results together
      for a more reliable conclusion. METHODS: The association of ABCB1 C3435T
      polymorphism with ONFH susceptibility was estimated through calculated odds
      ratios (ORs) with their 95% confidence intervals (95% CIs). The Q-test was
      applied for detecting inter-study heterogeneity, whereas sensitivity analysis for
      identifying any study owning substantial influence on pooled results. Begg's
      funnel plot and Egger's test were employed to examine publication bias across
      included studies. RESULTS: ABCB1 C3435T polymorphism significantly decreased the
      risk of ONFH under TT vs CC (OR = 0.26, 95% CI = 0.13-0.50), TT+CT vs CC (OR =
      0.72, 95% CI = 0.52-0.99), TT vs CC+CT (OR = 0.28, 95% CI = 0.15-0.52), and T vs
      C (OR = 0.64, 95% CI = 0.50-0.81) contrasts. CONCLUSION: The variant C3435T in
      the ABCB1 gene may offer protection against the attack of ONFH, and more studies
      with larger sample sizes should be conducted to certify this issue.

PMID- 28514286
TI  - Trends in diagnosis of painful neck and back conditions, 2002 to 2011.
AB  - Neck and back pain are pervasive problems. Some have suggested that rising
      incidence may be associated with the evidence of rising prevalence.To describe
      the trends in diagnosis of painful neck and back conditions in a large national
      healthcare system.A retrospective observational cohort study to describe the
      incidence and prevalence of diagnosis of neck and back pain in a national
      cohort.Patients were identified by International Classification of Diseases, 9
      Revision (ICD-9) codes in Department of Veterans Affairs (VA) national
      utilization datasets in calendar years 2002 to 2011.Descriptive statistics were
      used to analyze the data. Prevalent cases were compared with all veterans who
      sought health care in each year. Incident cases were identified following a 2
      years clean period in which the patient was enrolled and received care, but not
      services for any back or neck pain conditions.From 2004 to 2011, 3% to 4% of the
      population was diagnosed with incident back pain problems, the rate increasing on
      average, 1.75% per year. During the same period, 12.3% to 16.2% of the population
      was diagnosed with a prevalent back pain problem, the rate increasing on average
      4.09% per year.In a national population, the prevalence rate for diagnosis of
      neck and back pain grew 1.8 to 2.3 times faster than the incidence rate. This
      suggests that the average duration of episodes of care is increasing. Additional
      research is needed to understand the influences on the differential rate of
      change and to develop efficient and effective care systems.

PMID- 28514287
TI  - Concurrent IgG4-related tubulointerstitial nephritis and IgG4 myeloperoxidase
      anti-neutrophil cytoplasmic antibody positive crescentic glomerulonephritis: A
      case report.
AB  - RATIONALE: IgG4-related disease (IgG4-RD) is a newly recognized systemic disease.
      The typical pathological finding in the kidney is abundant IgG4-positive plasma
      cell infiltration with characteristic storiform fibrosis in the interstitium.
      Antibodies of the IgG4 subclass have been linked to certain autoimmune diseases
      including antiproteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) of
      the IgG4 subclass. Here, we report a rare case of kidney injury with concurrent
      typical IgG4-related tubulointerstitial nephritis and IgG4 subclass of
      myeloperoxidase (MPO) ANCA-positive necrotizing crescentic glomerulonephritis.
      PATIENT CONCERNS: A 42-year-old Chinese man presented with repeated epigastric
      pain, sausage-shaped pancreas observed morphologically in computed tomography,
      effectiveness of prednisone therapy and was diagnosed with autoimmune
      pancreatitis. He subsequently developed acute kidney injury. DIAGNOSES: The
      patient had an elevated serum IgG4, eosinophilia, and positive MPO-ANCA of IgG4
      dominant subclass. Renal biopsy revealed necrotizing crescentic nephritis and
      typical IgG4-related tubulointerstitial nephritis. INTERVENTIONS: The patient was
      treated with a combination of corticosteroids and cyclophosphamide, and a course
      of rituximab was later added to deplete peripheral B cells. OUTCOMES: The patient
      responded well and his renal function improved. LESSONS: This is the first case
      report of an IgG4-RD with concurrent IgG4-related tubulointerstitial nephritis
      and IgG4 MPO-ANCA-associated necrotizing crescentic glomerulonephritis. It raises
      the difficulty in differentiation diagnosis of the two separate diseases that is
      worthy of further study.

PMID- 28514288
TI  - Bordetella parapertussis outbreak in Southeastern Minnesota and the United
      States, 2014.
AB  - Whooping cough is traditionally ascribed to Bordetella pertussis; however,
      Bordetella parapertussis can cause a similar clinical syndrome. This study
      describes an outbreak of B. parapertussis in Southeastern Minnesota and the
      United States (US) in 2014. This was a retrospective analysis of Mayo Clinic and
      Mayo Medical Laboratories patients who tested positive for B. parapertussis from
      2012 to 2014. The medical records of Mayo Clinic patients who tested positive in
      2014 were reviewed for demographic information, presenting symptoms, disease
      course, and vaccination history. In Southeast Minnesota, 81% of the 31 patients
      who tested positive for B. parapertussis in 2014 were found to be positive from
      October through December. Their mean age was 5.9 years. Five reported "exposure
      to pertussis." Two pairs of siblings were affected. Patients reported having had
      symptoms for an average of 2.6 weeks before nasopharyngeal specimen collection
      for B. parapertussis testing. Cough was the primary symptom reported. Forty
      percent reported posttussive vomiting, 40% coryza, 32% apnea/sleep disturbance,
      and 12% sore throat. All were current with pertussis vaccination. Based on the
      review of national data, an outbreak occurred nationally in the Northeast and
      Midwest US over the same time period. In 2014, there was an outbreak of B.
      parapertussis in Southeastern Minnesota and likely other parts of the US. The
      presenting illness was similar to that of B. pertussis. All patients were
      vaccinated against pertussis, suggesting that pertussis vaccination is
      ineffective against B. parapertussis.

PMID- 28514289
TI  - Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer
      patients with liver metastasis.
AB  - The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with
      dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients
      with liver metastasis.A total of 50 CRC patients with liver metastasis who
      received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were
      recruited into the present study. Before the study (d0), and 3, 7, 14, and 42
      days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor
      perfusion was evaluated quantitatively by retention time (RT), peak enhancement
      (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake
      curve determined with original linear data.Routine ultrasonography was used to
      evaluate metastatic foci in the liver at baseline. A metastatic focus was
      selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to
      8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time
      points, including RT, PE, and WiAUC, showed that RT at baseline was significantly
      different between groups (P < .001; Responder group: 10.54 seconds; nonresponder
      group: 15.33 seconds). The2 groups had opposite changes in RT (continuous
      increase in the responder group and transient reduction in the nonresponder). The
      RT of metastatic foci was normalized to that of adjacent normal liver as standard
      RT-quotient, a similar trend was observed, and no marked difference was noted in
      the standard RT-quotient between the 2 groups. The median progression-free
      survival was significantly higher in the increased-RT group (10.8 months) than
      the decreased-RT group (2.5 months) (P = .002). There were no significant
      differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used
      to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients
      who received bevacizumab-based chemotherapy.

PMID- 28514290
TI  - The relationship between iodine intake and the risk of thyroid cancer: A meta
      analysis.
AB  - Thyroid cancer (TC) is the most common malignancy of the endocrine system. The
      relationship between iodine intake and TC risk is controversial always. We aim to
      figure out the relationship between iodine intake and TC using meta-analysis.
      Literature research in MEDLINE, Embase, China National Knowledge Infrastructure,
      and China BioMedicine was performed up to April 2016, searched for relevant case
      control and cohort studies. The effect of iodine consumption on the risk of TC
      was assessed using the pooled odds ratio (OR) and 95% confidence interval (CI).
      The meta-analysis included 8 case-control studies (n = 4974; 2213 cases; 2761
      controls). More than adequate or excess iodine intake (>300 MUg/d) decreased the
      risk of TC (OR 0.74, 95% CI 0.60, 0.92). High consumption of saltwater fish or
      shellfish decreased the risk of TC (OR 0.72, 95% CI 0.55, 0.95; OR 0.70, 95% CI
      0.52, 0.96; respectively). A higher intake of dietary iodine was as a protective
      factor for TC. However, the available data are very limited and more studies are
      required.

PMID- 28514291
TI  - Role of microRNA-130a in the pathogeneses of obstructive sleep apnea hypopnea
      syndrome-associated pulmonary hypertension by targeting the GAX gene.
AB  - OBJECTIVE: The purpose of this study was to elucidate the role of microRNA-130a
      (miR-130a) in obstructive sleep apnea hypopnea syndrome (OSAHS)-associated
      pulmonary hypertension (PHT) by targeting the growth arrest-specific homeobox
      (GAX) gene. METHODS: A total of 108 patients with OSAHS-associated PHT were
      recruited as the OSAHS-associated PHT group and 110 healthy individuals were
      randomly selected as the normal control group. Human umbilical vein endothelial
      cells (HUVECs) were selected and divided into the control, miR-130a mimic, mimic
      negative control (NC), miR-130a inhibitor, and inhibitor-NC groups. The dual
      luciferase reporter gene assay was used to identify the relationship between miR
      130a and the GAX gene. The quantitative real-time polymerase chain reaction (qRT
      PCR) and Western blotting were applied for the relative expressions of miR-130a
      and the mRNA and protein expressions of GAX. Serum levels of endothelin-1 (ET-1),
      vascular endothelial growth factor (VEGF), nitric oxide (NO), and super oxide
      dismutase (SOD) were detected. Cell apoptosis and angiogenic activity were
      analyzed by flow cytometry and cell tube formation assay. RESULTS: GAX was a
      target gene of miR-130a. Compared with the normal control group, the relative
      expression of miR-130a and the serum levels of ET-1 and VEGF were increased,
      whereas the mRNA expression of GAX and the serum levels of NO and SOD were
      decreased in the OSAHS-associated PHT group. Compared with the control, mimic-NC,
      and inhibitor-NC groups, the relative expressions of miR-130a in the miR-130a
      mimic group were enhanced, whereas the expression of miR-130a in the miR-130a
      inhibitor group was reduced. However, the mRNA and protein expressions of GAX
      showed an opposite trend in the miR-130a mimic and miR-130a inhibitor groups. In
      comparison to the control, mimic-NC, and inhibitor-NC groups, the miR-130a mimic
      group had an increase of ET-1 and VEGF expressions, whereas the expressions of NO
      and SOD were reduced. However, the miR-130a inhibitor group exhibited an opposite
      trend. The apoptosis rate and tube formation number in the miR-130a mimic group
      were obviously increased, whereas the miR-130a inhibitor group showed an obvious
      decrease. CONCLUSION: These data provided strong evidence that miR-130a may be
      involved in the progression of OSAHS-associated PHT by down-regulating GAX gene.

PMID- 28514292
TI  - Isolated olecranon fractures in children affected by osteogenesis imperfecta type
      I treated with single screw or tension band wiring system: Outcomes and pitfalls
      in relation to bone mineral density.
AB  - The purpose of this study is to compare the results of 2 techniques, tension band
      wiring (TBW) and fixation with screws, in olecranon fractures in children
      affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21
      olecranon fractures in 18 children with OI (average age: 12 years old) were
      treated surgically. Ten patients were treated with the screw fixation and 11 with
      TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous
      avulsion of the olecranon during the contraction of the triceps muscle. The
      average follow-up was 36 months. Among the children treated with 1 screw, 5
      patients needed a surgical revision with TBW due to a mobilization of the screw.
      In this group, the satisfactory results were 50%. In patients treated with TBW,
      the satisfactory results were 100% of the cases. The average Z-score, the last
      one recorded in the patients before the trauma, was -2.53 in patients treated
      with screw fixation and -2.04 in those treated with TBW. TBW represents the
      safest surgical treatment for patients suffering from OI type I, as it helps to
      prevent the rigidity of the elbow through an earlier recovery of the range of
      motion, and there was no loosening of the implant. In analyzing the average Z
      score before any fracture, the fixation with screws has an increased risk of
      failure in combination with low bone mineral density.

PMID- 28514293
TI  - The role of circulating miR-146a in patients with rheumatoid arthritis treated by
      Tripterygium wilfordii Hook F.
AB  - Rheumatoid arthritis (RA) is polygenic autoimmune disease with unclear etiology.
      MicroRNAs (miRNAs) play a critical role in the pathogenesis of RA. The objective
      of this study was to evaluate the role of miR-146a in patients with RA receiving
      Tripterygium wilfordii Hook F (TwHF) treatment.In total, 69 patients with RA and
      69 healthy controls (HC) were included in the study, and patients with RA
      received TwHF treatment for 24 weeks. Blood samples were collected from RA
      patients and HC, and peripheral blood mononuclear cells (PBMCs) were isolated.
      Expression of miR-146a was analyzed in RA patients (baseline, 12 weeks and 24
      weeks) and HC.Circulating miR-146a expression was markedly increased in patients
      with RA compared with healthy controls (P < .001), ROC analysis of miR-146a for
      diagnosis for RA showed that the AUC was 0.908 (95% CI: 0.862-0.955) with a
      sensitivity of 87.0% and a specificity of 82.6% at best cutoff. And miR-146a
      expression was positively associated with the DAS28 score and CRP level (P = .002
      and P = .019). Moreover, miR-146a expression was markedly reduced after TwHF
      therapy (P < .001), and baseline miR-146a level was observed to present an
      increased tendency in responders compared with non-responders at 24 weeks (P =
      .066).Our study presented that circulating miR-146a level was correlated with
      risk and disease activity of RA patients by TwHF treatment, which could
      strikingly decrease expression of miR-146a in RA patients, and miR-146a may have
      a value in predicting clinical response of TwHF treatment. It indicates that
      circulating miR-146a plays a prominent role in RA patients treated by TwHF.

PMID- 28514294
TI  - TNFAIP3 gene rs7749323 polymorphism is associated with late onset myasthenia
      gravis.
AB  - In this study, we intended to genotype 2 single nucleotide polymorphisms (SNPs)
      of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) genes and explore an
      association of TNFAIP3 genetic polymorphism with the patients of myasthenia
      gravis (MG) at clinical level. In brief, 215 of adult MG patients were divided
      into subgroups according to their clinical features, age of onset, thymic
      pathology, and autoantibodies. Two hundred thirty-five of healthy controls were
      also divided into subgroups with gender- and age-matched. The allele and genotype
      frequencies of subgrouped patients were found to be higher than those of healthy
      controls. The distribution of TNFAIP3 gene rs7749323*A allele of late onset MG
      (LOMG, with positive acetylcholine receptor antibody and without thymoma)
      subgrouped patients was also significantly higher than that of gender- and age
      matched healthy controls (7.4% vs 2.4%, odds ratio [OR] = 3.27, 95% confidence
      interval [CI] 1.01-10.6, P = .04). Furthermore, analysis to the genotype
      frequencies indicates that the carriers of rs7749323*A allele of LOMG group
      became more frequent than that of age-matched healthy controls (14.9% vs 4.8%, OR
      = 3.47, 95% CI 1.04-11.6, dominant model: P = .03). It is interesting to notice
      that there is no significant association between the rs7749323 and susceptibility
      of other MG subgroups. Therefore, it is suggested that the SNPs in the 3'
      flanking region (rs7749323) of TNFAIP3 gene and the genetic variations of TNFAIP3
      gene may take an important role in the susceptibility of LOMG.

PMID- 28514295
TI  - Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis
      in chronic hepatitis B: A cross-sectional study of diagnostic accuracy.
AB  - Cell death markers, M65 and M30, have been suggested to be sensitive markers of
      liver inflammation and fibrosis in nonalcoholic fatty liver disease and chronic
      hepatitis C. Our aim was to investigate whether these markers were useful in
      diagnosing liver inflammation and fibrosis in chronic hepatitis B (CHB).We
      examined 186 patients with CHB; 18 sex- and age-matched healthy subjects were
      controls. The blood samples were collected from CHB patients within 1 week before
      or after liver biopsy. According to METAVIR score system, liver inflammation was
      graded from A0 to A3, and fibrosis from F0 to F4.Serum M65 and M30 levels were in
      parallel with the grades of liver inflammation. M65, not M30, increased
      significantly in patients with severe inflammation and normal alanine
      aminotransferase. M65 is one of the independent predictors of severe liver
      inflammation (>=A2). The levels of M65 and M30 levels significantly increased in
      parallel with the degree of inflammation in F1 patients, whereas they showed no
      statistical difference between different stages of fibrosis in A1 patients.Serum
      M65 is a useful indicator of liver inflammation in CHB patients. Serum M65, not
      M30, is valuable in the grading of liver fibrosis.

PMID- 28514296
TI  - Clinicopathological features and differential diagnosis of aggressive angiomyxoma
      of the female pelvis: 5 case reports and literature review.
AB  - Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that usually occurs in
      the pelvis and perineum of young females. AAM can simulate Bartholin's gland
      cyst, abscess, lipoma, simple labial cyst, or other pelvic soft tissue tumors.
      Here we present five cases of AAM with mean age of 42. The patients mainly
      presented slow-growing mass in the abdomen and perineum (3 cases in the pelvis, 1
      in the vulva, and 1 in the buttock). Color Doppler flow imaging revealed blood
      flow for the 3 pelvic lesions. Enhanced computed tomography and magnetic
      resonance imaging of the other 2 cases showed the typical "swirled" or "layered"
      structure characteristic. Through the pathological examination, its positivity to
      estrogen and progesterone receptors can justify enlargement and recurrence,
      confirming the tumor is AAM. All 5 patients underwent local tumor resection. Two
      patients recurred 8 and 15 months after surgery, respectively. The longest follow
      up was 42 months. Although few cases are reported, early recognition demands high
      index of suspicion for both gynaecologists and pathologists. Wide surgical
      excision with tumor free margins is the basis of curative treatment. Adjuvant
      therapy may be necessary for residual or recurrent tumors. Long-term follow-up is
      recommended.

PMID- 28514297
TI  - Association of single-nucleotide polymorphisms in toll-like receptor 2 gene with
      asthma susceptibility: A meta-analysis.
AB  - BACKGROUND: An increasing number of studies have been carried out on the
      relationship between polymorphisms in toll-like receptor 2 (TLR2) gene and asthma
      risk. However, the results were controversial. With the purpose of yielding a
      more reliable estimation of the association, we conducted the present meta
      analysis. METHODS: Multiple electronic databases up to August 22, 2016 were
      searched for literature retrieval. The association between the asthma
      susceptibility and the rs5743708 polymorphism, rs3804099 polymorphism, rs3804100
      polymorphism, and rs4696480 polymorphism in TLR2 gene was appraised. The odds
      ratios (ORs) with 95% confidence intervals (CIs) under different genetic models
      were calculated. RESULTS: A total of 13 studies were eligible in our meta
      analysis according to the predefined inclusion and exclusion criteria. There was
      no significant association between asthma risk and rs5743708, rs3804099, and
      rs3804100 polymorphisms in TLR2 gene under any genetic model. With respect to the
      TLR2 rs4696480 polymorphism, significant association was detected between asthma
      susceptibility and TLR2 rs4696480 polymorphism under dominant model (OR = 2.455,
      95% CI = 1.235-4.88, P = .01) and codominant 3 model (OR = 2.776, 95% CI = 1.199
      6.427,  = 0.017). CONCLUSIONS: Our meta-analysis reveals that the TLR2 rs4696480
      polymorphism is significantly associated with asthma susceptibility, and the TLR2
      rs4696480 polymorphism is a risk factor for asthma.

PMID- 28514298
TI  - Association between common polymorphisms in ERCC gene and glioma risk: A meta
      analysis of 15 studies.
AB  - BACKGROUND: A number of studies have investigated the roles of excision repair
      cross complementation group 1 (ERCC1), ERCC2, and ERCC5 genes polymorphisms in
      the development of glioma; however, the results were inconsistent. Here, we
      performed a meta-analysis to investigate the association between 6 polymorphisms
      in the ERCC genes (rs3212986, rs11615, rs13181, rs1799793, rs238406, rs17655) and
      glioma risk. METHODS: The PubMed, Embase, and Web of science were searched up to
      September 6, 2016, for studies on the association between ERCC polymorphisms and
      glioma risk. A fixed-effects or random-effects model was used to calculate the
      pooled odds ratios based on the results from the heterogeneity tests. Sensitivity
      and cumulative meta-analyses were also performed. RESULTS: A total of 15 studies
      were eligible for the pooled analysis, conducted in 2 populations of ethnic
      descent: 8 Europeans and 7 Asians. The results showed that ERCC1 rs3212986
      polymorphism was positively associated with glioma [AA vs CC: odds ratio (OR) =
      1.298, 95% confidence interval (95% CI) = 1.043-1.230, P = .025]. Association of
      the ERCC2 rs13181 and rs1799793 polymorphisms was only observed in Asians (CC vs
      AA for rs13181: OR = 1.539, 95% CI = 1.122-2.109, P = .007; AA vs GG for
      rs1799793: OR = 1.474, 95% CI = 1.090-1.994, P = .012). However, no association
      was observed between glioma risk and ERCC1 rs11615, ERCC2 rs238406, and ERCC5
      rs17655 polymorphisms. Moreover, sensitivity and cumulative meta-analyses
      confirmed the stability of the results. CONCLUSIONS: Our meta-analysis indicated
      that the ERCC1 rs3212986 polymorphism and 2 polymorphisms in ERCC2 gene (rs13181
      and rs1799793) contributed to the susceptibility of glioma.

PMID- 28514299
TI  - Application of a buprenorphine transdermal patch for the perioperative analgesia
      in patients who underwent simple lumbar discectomy.
AB  - This study aimed to investigate the perioperative analgesic effect of a
      buprenorphine transdermal patch in patients who underwent simple lumbar
      discectomy.In total, 96 patients were randomly divided into parecoxib intravenous
      injection (Group A), oral celecoxib (Group B), and buprenorphine transdermal
      patch groups (Group C). The pain status, degree of satisfaction, adverse effects,
      and condition in which the patient received tramadol hydrochloride for
      uncontrolled pain were recorded on the night before surgery, postoperative day 1,
      postoperative day 3, and postoperative day 5.The degree of patient satisfaction
      in Group C was higher than that in Groups A and B, with minimal adverse
      effects.The buprenorphine transdermal patch had a better perioperative analgesic
      effect in patients who underwent simple lumbar discectomy.

PMID- 28514300
TI  - Increasing efficacy and reducing side effects in treatment of chronic anal
      fissures: A study of topical diazepam therapy.
AB  - This is a single institution nonexperimental study intended to analyze the
      therapeutic efficacy of topical diazepam in treating symptoms of chronic anal
      fissures.Anal fissures are a common cause of anal pain. Conventional treatments
      include nonsteroidal anti-inflammatory drugs, topical creams, such as
      nitroglycerin and nifedipine, and surgery. However, these treatments are usually
      suboptimally efficacious or have deterring side effects.Patients at an outpatient
      community center with a diagnosis of a chronic anal fissure were prescribed
      either topical 2% (n = 19) or 4% (n = 18) diazepam cream between January 2013 and
      February 2015. We retrospectively analyzed their responses to treatment.All 19
      patients using 2% diazepam cream experienced a positive response in pain, whereas
      47.4% experienced a complete response, with a numerical rating scale (NRS) score
      of 0 (0-10). Eighty-eight percent of patients using 4% dose had a positive
      response in pain, whereas 23.5% experienced a complete response. Ninety-four
      percent of patients using 2% dose had a positive response in anal bleeding,
      whereas 68.8% experienced a complete response with an anal bleeding score (ABS)
      of 2 (2-9). Ninety-four percent of patients using 4% dose had a positive response
      in anal bleeding, whereas 64.7% experienced a complete response. Only 1 patient
      reported a side effect from diazepam cream-perianal pruritus.Both 2% and 4%
      topical diazepam provided significant pain and bleeding relief from chronic anal
      fissures that were refractory to conventional therapies. There were insignificant
      differences when assessing independent comparisons for pain and bleeding between
      the doses.

PMID- 28514301
TI  - Unusual axillary metastasis of recurrent nasopharyngeal cancer: A case report.
AB  - RATIONALE: Nasopharyngeal carcinoma (NPC) has a high propensity of metastasis.
      The most commonly described sites of distant metastasis are the bones, lungs, and
      liver, whereas axillary metastasis is seldom reported. PATIENT CONCERNS: We
      hereby present the case of a 66-year-old man with NPC, cT2N2M0, at diagnosis. He
      had completed chemoradiotherapy and been disease-free for 7 years. DIAGNOSES:
      After that period, late recurrence in the form of a solitary axillary lymph node
      metastasis was detected and confirmed by core-needle biopsy. INTERVENTIONS: The
      lesion was chemoresistant but responded to salvage radiotherapy at a dose of 65
      Gy in 21 fractions. OUTCOMES: Post-radiotherapy positron emission tomography scan
      showed no evidence of disease. LESSONS: We suggested that long-term follow-up of
      NPC patients is important because a late relapse may occur at an unusual site.
      Aggressive management of solitary metastasis may achieve good outcome.

PMID- 28514302
TI  - Safety and efficacy evaluation of pertuzumab in patients with solid tumors.
AB  - BACKGROUND: The development of targeted therapies benefits patients with certain
      markers in the treatment of breast cancer. Pertuzumab is a novel humanized
      monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2)
      dimerization. The Food and Drug Administration has approved pertuzumab in
      combination with trastuzumab and docetaxel for the treatment of patients with
      HER2-positive metastatic breast cancer. METHODS: To assess the safety and
      efficacy profile of pertuzumab, we searched PubMed and Embase (articles from
      January 1966 to January 2015) using the keyword "pertuzumab". RESULTS: Fourteen
      eligible studies were included in our final analysis. From the results of our
      analysis, diarrhea (56.9%, 95% confidence interval [CI] 49.6%-63.9%), nausea
      (34.0%, 95% CI 27.7%-40.8%), and rash (25.6%, 95% CI 20.8%-31.0%) were the most
      common adverse effects in pertuzumab alone and pertuzumab-based therapies. Based
      on randomized controlled clinical trials, diarrhea (odds ratio [OR] 2.310, 95% CI
      1.818-2.936), rash (OR 1.848, 95% CI 1.094-3.122), and febrile neutropenia (OR
      1.672, 95% CI 1.130-2.474) were of statistical significance, which meant that
      pertuzumab played a prominent role in the incidence of diarrhea. Meanwhile,
      pertuzumab showed its effective role in cancer control and lifetime prolongation.
      CONCLUSION: In conclusion, considering that the common adverse effects for
      pertuzumab are gastrointestinal and skin toxicities, which are easier to handle
      than other toxicities, pertuzumab is a safe and effective drug for patients with
      solid tumors.

PMID- 28514303
TI  - Continuous venovenous hemofiltration in the management of paraquat poisoning: A
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Paraquat (PQ) poisoning is a widespread occurrence, especially in
      underdeveloped areas. The treatment of PQ poisoning has always been difficult,
      and there is currently no definite effective treatment. Continuous venovenous
      hemofiltration (CVVH) treatment for PQ poisoning has been widely used in clinical
      practice; however, its effect remains uncertain. Accordingly, the purpose of this
      meta-analysis was to evaluate the efficacy of CVVH in the treatment of PQ
      poisoning. METHODS: We searched for relevant trials using PubMed, Embase, the
      Cochrane Library, and 3 Chinese databases, the Chinese BioMedical Literature
      Database, National Knowledge Infrastructure Database, and Wanfang Database. We
      included all qualified randomized controlled trials (RCTs) of CVVH treatment for
      patients with PQ poisoning. The primary outcome was mortality, while the
      secondary outcomes included the survival time and constituent ratios of death due
      to respiratory failure and circulatory failure. RESULTS: Three RCTs involving 290
      patients were included. The mortality rates of the intervention and control
      groups were 57.9% and 61.0%, respectively. Pooled analysis demonstrated no
      significant difference in mortality between the CVVH treatment and control groups
      (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.78-1.15, P = .56), with a
      low level of heterogeneity (X = 1.75, I = 0%). However, the CVVH group was
      associated with a longer survival time compared to the control group (weighted
      mean difference 1.73, 95% CI: 0.56-2.90, P = .004). Respiratory failure as the
      cause of death was more common in the CVVH group, as compared with the control
      group (RR 1.66, 95% CI: 1.24-2.23, P = .0008), whereas patients in the control
      group were more likely to die from circulatory failure than in the CVVH group (RR
      0.56, 95% CI: 0.40-0.81, P = .002). CONCLUSION: Although CVVH treatment might not
      noticeably reduce mortality for patients with PQ poisoning, it can prolong the
      survival time of the patients and improve the stability of the circulatory
      system, thereby enabling further treatment.

PMID- 28514304
TI  - Diagnostic and clinical application value of magnetic resonance imaging (MRI) for
      progressive massive fibrosis of coal worker pneumoconiosis: Case reports.
AB  - RATIONALE: Using magnetic resonance imaging (MRI), we diagnosed pneumoconiosis by
      identifying the content and distribution of hydrogen protons in the water
      molecules in different tissues and lesions. PATIENT CONCERNS: 25 cases of CWP
      patients with progressive massive fibrosis (PMF) lesions. DIAGNOSES: Patients
      were correctly diagnosed, with one case each of Phase I and II pneumoconiosis and
      23 cases of Phase III pneumoconiosis. INTERVENTIONS: None. OUTCOMES: Through MRI,
      39 PMF pneumoconiosis lesions exhibited equal, low or equally low, and uneven
      signals on T2WI and fat suppression (SPIR) (38/39, 37/39). LESSONS: MRI has good
      specificity to identify the characteristics of PMF lesions of CWP, as well as has
      high application value for the differential diagnosis of lung cancer and other
      lung tumor-like lesions.

PMID- 28514305
TI  - Explaining trends and variation in timing of dialysis initiation in the United
      States.
AB  - The United States Renal Data System (USRDS) registry of end-stage renal disease
      has often been used to study the timing of dialysis initiation, measured by
      estimated glomerular filtration rate (eGFR) at dialysis initiation. We conducted
      an observational study and examined how well variables in the USRDS database
      explain the trends and variation in eGFR at dialysis initiation.We identified
      971,481 patients who initiated dialysis between 1995 and 2012 in the USRDS
      registry.The mean eGFR at dialysis initiation monotonically rose from 7.7 in 1995
      to 11.1 in 2009, and then leveled off to 10.9 mL/min/1.73 m in 2012. The trend of
      rising, then leveling off was similar across all subgroups studied. Substantial
      variation in eGFR at dialysis initiation was observed, with standard deviation of
      4.38 (95% CI: 2.0-18.4). A total of 11.4% of the total variation occurred across
      physicians and 88.6% within physicians. Adjustment for measured factors only
      modestly decreased the total variation. Of the total variance, 10.7% was
      explained by measured patient-level variables and 1.2% by measured physician and
      other factors, while 9.2% of physician-level variation and 78.9% of patient-level
      variation remained unexplained. The extent of variation explained by measured
      variables was similar over the entire study period.The finding that the majority
      of variation in eGFR at dialysis initiation is unexplained by measured variables
      casts doubt on how well eGFR serves as a measure for "timing" of dialysis
      initiation, and it indicates the need to collect more focused data to gain
      understanding of factors that affect timing of dialysis initiation in the US.

PMID- 28514306
TI  - Unusual case of rapid growing intraabdominal abscess caused by Stenotrophomonas
      maltophilia after laparoscopic appendectomy due to perforated appendicitis: A
      case report.
AB  - INTRODUCTION: An intraabdominal abscess due to Stenotrophomonas maltophilia (S
      maltophilia) infection is a very rare clinical manifestation. S maltophilia is a
      glucose nonfermentative, aerobic, gram-negative, mobile, and biofilm-forming
      bacterium. It is an opportunistic pathogen and uncommon cause of infection.
      Respiratory tract infections (pneumonia) and bloodstream infections (bacteremia)
      are the most common clinical manifestations of S maltophilia infection.
      CONCLUSIONS: This case report describes an unusual case of a rapidly growing,
      extremely large intraabdominal abscess (within 1 week during antibiotic therapy),
      which was detected 2 weeks after a laparoscopic appendectomy was performed for
      perforated appendicitis and was caused by multidrug-resistant S maltophilia
      infection.

PMID- 28514307
TI  - Exome sequencing identifies a de novo mutation of CTNNB1 gene in a patient mainly
      presented with retinal detachment, lens and vitreous opacities, microcephaly, and
      developmental delay: Case report and literature review.
AB  - RATIONALE: The CTNNB1 (beta-catenin) gene is well known for its crucial role in
      cell adhesion and the Wnt-signaling pathway. Previous studies have shown that
      gain-of-function mutations in the CTNNB1 gene contribute to the occurrence and
      development of a variety of carcinomas in humans. Recently, de novo,
      heterozygous, loss-of-function mutations of the CTNNB1 gene were found that
      partially explain intellectual disability in some patients. Other major clinical
      symptoms in these patients included microcephaly, abnormal facial features, motor
      delays, speech impairments, and deformities of the hands and feet. In addition,
      approximately 75% of these patients had mild visual defects, such as astigmatism,
      hyperopia, or strabismus PATIENT CONCERNS:: A 15-month-old Chinese boy,
      presenting with retinal detachment, lens and vitreous opacities, hypertonia of
      the extremities, mild thumb adduction, microcephaly, and developmental delay, is
      described. Targeted gene sequencing using an ophthalmic gene panel was performed
      to test for familial exudative vitreoretinopathy; however, the pathogenic gene
      was not found. INTERVENTIONS: Genomic DNA analysis was performed to search for
      causing mutations. DIAGNOSES AND OUTCOMES: Whole-exome sequencing revealed a
      novel nonsense variation in exon 11 of the CTNNB1 gene (c.1672C>T, p.Gln558X).
      Sanger sequencing of the patient and his parent confirmed this mutation and
      demonstrated it to be de novo. To the best of our knowledge, this is the first
      case report of a loss-of-function mutation of the CTNNB1 gene in an Asian
      population. LESSONS: Severe ophthalmic phenotype has not well been connected with
      loss of functional mutation of CTNNB1 gene. Our finding expands the mutant
      spectrum of CTNNB1 gene and adds new understanding of the phenotype.

PMID- 28514308
TI  - Emotional exhaustion-induced latent autoimmune diabetes in adults in a young
      lady: A CARE-compliant case report.
AB  - RATIONALE: Latent autoimmune diabetes in adults (LADA) refers to an autoimmune
      disorder characterized with detectable islets antibodies in the early diagnosis
      and increased autoimmune beta-cell failure progression. Notably, this kind of
      diabetes seems to be confused with other phenotypic diabetes. PATIENT CONCERNS: A
      young woman suffered an emotional exhaustion-induced LADA, showing asthenia,
      polydipsia, polyuria, and visible weight loss. The patient emotionally ended a 14
      year romantic relationship, leading to the emotional flooding. DIAGNOSES: The
      data from physical examination and laboratory tests exhibited as follows:
      glutamic acid decarboxylase antibody (GADA) = 63.83 U/mL, the fasting blood
      glucose (FBG) = 13.3 mmol/L, and glycated haemoglobin (HbA1c) = 10.9%. According
      to levels of GADA, the patient was diagnosed as LADA. INTERVENTIONS: The patient
      was clinically treated with insulin for 3-month. Then, running, diet-control, and
      emotional treatment were combined, such as the patient started a new
      relationship. OUTCOMES: An emotional recovery initiated from a new romantic
      relationship and a baby, showing normal levels of GAD65 (27.007 IU/mL) and FBG
      (5.46) mmol/L. LESSONS: The emotional exhaustion might play a significant role in
      induction of LADA. It is important that individuals should maintain optimism,
      cheer, and a positive attitude.

PMID- 28514309
TI  - A randomized controlled trial of botulinum toxin A for treating neuropathic pain
      in patients with spinal cord injury.
AB  - BACKGROUND: To assess the effect of botulinum toxin A (BTA) for treating
      neuropathic pain in patients with spinal cord injury (SCI). METHODS: A total of
      44 patients with SCI with neuropathic pain were randomly divided into the
      intervention group and the placebo group, each group 21 patients. The subjects in
      the intervention group received BTA (200 U subcutaneous injection, once daily) at
      the painful area, whereas those in the placebo group were administered a saline
      placebo. This study was conducted from December 2014 to November 2016. The
      primary outcome was measured using the visual analog scale (VAS). The secondary
      outcomes were measured using the short-form McGill Pain Questionnaire (SF-MPQ),
      and World Health Organization quality of life (WHOQOL-BREF) questionnaire. All
      outcome measurements were performed before and after 4 and 8 weeks of
      intervention. RESULTS: Forty-one participants completed the study. The
      intervention with BTA showed greater efficacy than placebo in decreasing the VAS
      score after week 4 and week 8 of treatment. Significant differences in the SF-MPQ
      and WHOQOL-BREF were also found between the 2 groups. CONCLUSION: The results of
      this study demonstrated that BTA might decrease intractable neuropathic pain for
      patients with SCI.

PMID- 28514310
TI  - Development and validation of a mortality risk model for pediatric sepsis.
AB  - Pediatric sepsis is a burdensome public health problem. Assessing the mortality
      risk of pediatric sepsis patients, offering effective treatment guidance, and
      improving prognosis to reduce mortality rates, are crucial.We extracted data
      derived from electronic medical records of pediatric sepsis patients that were
      collected during the first 24 hours after admission to the pediatric intensive
      care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014.
      A total of 788 children were randomly divided into a training (592, 75%) and
      validation group (196, 25%). The risk factors for mortality among these patients
      were identified by conducting multivariate logistic regression in the training
      group. Based on the established logistic regression equation, the logit
      probabilities for all patients (in both groups) were calculated to verify the
      model's internal and external validities.According to the training group, 6
      variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate
      levels, and mechanical ventilation in 24 hours) were included in the final
      logistic regression model. The areas under the curves of the model were 0.854
      (0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups,
      respectively.The Mortality Risk Model for Pediatric Sepsis we established in this
      study showed acceptable accuracy to predict the mortality risk in pediatric
      sepsis patients.

PMID- 28514311
TI  - Trends in esophageal and esophagogastric junction cancer research from 2007 to
      2016: A bibliometric analysis.
AB  - BACKGROUND: This study aimed to analyze the scientific outputs of esophageal and
      esophagogastric junction (EGJ) cancer and construct a model to quantitatively and
      qualitatively evaluate pertinent publications from the past decade. METHODS:
      Publications from 2007 to 2016 were retrieved from the Web of Science Core
      Collection database. Microsoft Excel 2016 (Redmond, WA) and the CiteSpace (Drexel
      University, Philadelphia, PA) software were used to analyze publication outcomes,
      journals, countries, institutions, authors, research areas, and research
      frontiers. RESULTS: A total of 12,978 publications on esophageal and EGJ cancer
      were identified published until March 23, 2017. The Journal of Clinical Oncology
      had the largest number of publications, the USA was the leading country, and the
      University of Texas MD Anderson Cancer Center was the leading institution. Ajani
      JA published the most papers, and Jemal A had the highest co-citation counts.
      Esophageal squamous cell carcinoma ranked the first in research hotspots, and
      preoperative chemotherapy/chemoradiotherapy ranked the first in research
      frontiers. CONCLUSION: The annual number of publications steadily increased in
      the past decade. A considerable number of papers were published in journals with
      high impact factor. Many Chinese institutions engaged in esophageal and EGJ
      cancer research but significant collaborations among them were not noted. Jemal
      A, Van Hagen P, Cunningham D, and Enzinger PC were identified as good candidates
      for research collaboration. Neoadjuvant therapy and genome-wide association study
      in esophageal and EGJ cancer research should be closely observed.

PMID- 28514313
TI  - Clinical and biological correlations in celiac disease in children: the
      prospective single experience of a romanian tertiary center: A case-control study
      (Strobe-Compliant study).
AB  - Celiac disease-a chronic inflammatory disease of the intestine-is triggered by
      gluten or associated protein consumption.The aim of our study was to assess the
      sensitivity, specificity of the combined anti-transglutaminase 2 (TG2)/deamidated
      gliadin peptide antibodies (DGP), and antiendomisium antibodies (EMA), to
      determine the distribution of HLA-DQ2/DQ8 for the 140 tested patients, and also
      to evaluate the clinical and laboratory characteristics of patients admitted with
      the suspicion of celiac disease (CD). Children included in the study were divided
      into: group 1, patients with confirmed CD; group 2, patients with "potential' CD;
      group 3, control group, patients without CD. We assessed the standard laboratory
      data, the level of TG2/DGP and EMA antibodies, as well as the distribution of HLA
      molecules in the selected patients. Histopathological examination was considered
      the criterion standard for diagnosis in most cases.The sensitivity of TG2/DGP was
      85% and the specificity 92%. EMA showed a sensitivity of 82% and a specificity of
      98%. The vast majority of patients diagnosed with CD were either HLA-DQ2.5
      (encoded by DQA1*05 & DQB1*02) positive (87.5%) or HLA-DQ8 (encoded by
      DQB1*03:02) positive (12.5%). One patient showed a positivity only for HLA-DQ2.2
      (encoded by DQA1*02 & B1*02).Our study showed that the genetic risk for CD was
      present in more than one-third of the cases without a confirmed diagnosis of CD.
      Therefore, the awareness of genetic susceptibility for CD is essential because of
      the fact that these individuals can develop the disease at any point of their
      lives. The sensitivity of TG2/DGP and EMA were very similar, whereas EMA
      presented a higher specificity as that of TG2/DGP.

PMID- 28514314
TI  - Infected tibia defect fractures treated with the Masquelet technique.
AB  - The treatment after open and infected fractures with extensive soft tissue damage
      and bone deficit remains a challenging clinical problem. The technique described
      by Masquelet, using a temporary cement spacer to induce a membrane combined with
      reconstructive soft tissue coverage, is a possible solution. This study describes
      the work-up, operative procedure, complications, and the outcome of a homogenous
      group of patients with an open and infected tibia fracture and segmental bone
      loss treated with the Masquelet technique (MT).This retrospective study evaluates
      patients having sustained an open tibia fracture treated with the MT between 2008
      and 2013 with a follow up of at least 1 year. The defect was either primary,
      caused by a high-grade open fracture or secondary due to a non-union after an
      open fracture. Prerequisite conditions prior to the procedure of the Masquelet
      were a defect zone with eradicated infection, an intact soft tissue cover and
      stability provided by an external fixation.Volume of the defect, time until the
      implantation of the spacer, time of the spacer in situ and the time to clinical
      and radiological union were evaluated. Patient records were screened for
      reoperations and complications. The functional clinical outcome was
      measured.Eight patients were treated with a follow up over 1 year. The spacer was
      implanted after a median of 11 (2-70) weeks after the accident. The predefined
      conditions for the Masquelet phase were reached after a median of 12 (7-34)
      operations.Seven patients required reconstructive soft tissue coverage. The
      volume of the defect had a median of 111 (53.9-621.6) cm, the spacer was in situ
      for a median of 12 (7-26) weeks. Radiological healing was achieved in 7 cases
      after a median time of 52 (26-93) weeks.Full weight bearing was achieved after a
      median time of 16 (11-24) weeks. Four patients needed a reoperation. The lower
      limb functional index was a median of 60% (32-92%).Seven out of 8 patients
      treated in this group of severe open and infected tibia fractures did both
      clinically and radiologically heal. Due to the massive destruction of the soft
      tissue, patients needed several reoperations with soft tissue debridements and
      reconstruction before the spacer and the bone graft could be implanted.

PMID- 28514312
TI  - Treatment inferred from mutations identified using massive parallel sequencing
      leads to clinical benefit in some heavily pretreated cancer patients.
AB  - Molecular portraits of numerous tumors have flooded oncologists with vast amounts
      of data. In parallel, effective inhibitors of central pathways have shown great
      clinical benefit. Together, this promises potential clinical benefits to
      otherwise end-stage cancer patients. Here, we report a clinical service offering
      mutation detection of archived samples using the ion Ampliseq cancer panel
      coupled with clinical consultation.A multidisciplinary think tank consisting of
      oncologists, molecular-biologists, genetic counselors, and pathologists discussed
      67 heavily pretreated, advanced cancer patient cases, taking into account
      mutations identified using ion Ampliseq cancer panel, medical history, and
      relevant literature.The team generated a treatment plan, targeting specific
      mutations, for 41 out of 64 cases. Three patients died before results were
      available. For 32 patients, the treating oncologists chose not to include the
      panel recommendation in the treatment plan for various reasons. Nine patients
      were treated as recommended by the panel, 5 with clinical benefit, and 4 with
      disease progression.This study suggests that routine use of massive parallel
      tumor sequencing is feasible and can judiciously affect treatment decisions when
      coupled with multidisciplinary team-based decision making. Administration of
      personalized based therapies at an earlier stage of disease, expansion of genetic
      alterations examined, and increased availability of targeted therapies may lead
      to further improvement in the clinical outcome of metastatic cancer patients.

PMID- 28514316
TI  - New idea for treatment strategies for Barcelona Clinic Liver Cancer stages based
      on a network meta-analysis.
AB  - BACKGROUND: Currently, the Barcelona Clinic Liver Cancer staging (BCLC) system
      still remains controversies in the management of hepatocellular carcinoma. We are
      trying to determine the best therapeutic strategy for each BCLC stage through a
      network meta-analysis and provide a new treatment idea. METHODS: We conducted a
      systematic literature search of the PubMed, EMBASE, and Cochrane Library
      databases and extracted data from randomized controlled trials (RCTs) that
      compared various strategies. Network meta-analyses were conducted in ADDIS by
      evaluating different overall survival of each stage. Cumulative probability was
      used to rank the included strategies. A node-splitting model assessed whether
      direct and indirect evidence on a specific node was in agreement. RESULTS: Of the
      24 included RCTs, 3667 patients were included. Based on the probability P values,
      the results showed that TACE plus surgical resection (SR) was the first choice
      for BCLC Stage A (P = .38 and P = .52 for 3- and 5-year OS, respectively). The
      application of SR was the best strategy for BCLC Stage B (P = .51 and P = .95 for
      1- and 3-year OS, respectively). For Stage C, whole net connections could not be
      established in this research, but combined therapy seemed to produce better
      results based on 3 separated net connections (P = .92, P = .80, and P = .69 for 1
      year OS). CONCLUSIONS: The updated therapy strategies discussed in this study are
      recommended. More importantly, we deemed that the recommended strategy for each
      patient may be subject to adjustment due to individual clinical factors. The
      applicable scope of each strategy should also be evaluated before application.

PMID- 28514315
TI  - Role of Cystatin C and glomerular filtration rate in diagnosis of kidney
      impairment in hepatic cirrhosis patients.
AB  - Hepatic cirrhosis is often accompanied by functional kidney impairment, which may
      be reversed if early treatment is promptly administered. This study aimed to
      investigate the role of Cystatin C and Cystatin C estimated glomerular filtration
      rate in the diagnosis of kidney impairment in patients with hepatic
      cirrhosis.Four hundred sixty five patients with hepatic cirrhosis were recruited.
      Serum creatinine and Cystatin C were determined, and their estimated glomerular
      filtration rates were calculated.The area under the receiver-operating
      characteristic curve (area under curve [AUC]) of Cystatin C and Cystatin C
      estimated glomerular filtration rate was significantly larger than that of serum
      creatinine and serum creatinine estimated glomerular filtration rate,
      respectively (P = .000). When the optimal cut-off value and upper reference limit
      were used, similar sensitivity, misdiagnosis rate, and diagnostic consistency
      were only observed in Cystatin C estimated glomerular filtration rate (P >
      .05).Cystatin C and Cystatin C estimated glomerular filtration rate are superior
      to serum creatinine and serum creatinine estimated glomerular filtration rate in
      diagnosis of secondary kidney impairment, and Cystatin C estimated glomerular
      filtration rate has a better performance as compared with Cystatin C. However, it
      is not a measured parameter, and thus the lab should determine its own optimal
      cut-off value.

PMID- 28514317
TI  - Impact of age on short-term outcomes of liver surgery: Lessons learned in 10
      years' experience in a tertiary referral hepato-pancreato-biliary center.
AB  - We investigate the surgical outcomes of patients undergoing hepatectomy according
      to different age intervals, identify the clinical factors related to surgical
      outcomes, and propose clinical risk scores for severe morbidity and mortality
      based on the clinical factors.Eight hundred three patients undergoing liver
      resection were divided into 3 groups: young patients (YP), <65 years (n = 387),
      elderly patients (EP), from 65 to 74 years (n = 279); very-elderly patients
      (VEP), >=75 years (n = 137).Severe morbidity was 10.6%, 12.2%, and 17.5% (P =
      .103), and mortality was 0.3%, 1.4%, and 4.4% (P = .002) in group YP, EP, and
      VEP, respectively. Ischemic heart disease, cirrhosis, major hepatectomy, biliary
      tract-associated procedure, and red blood cells (RBC) transfusion >=3 U were
      related with severe morbidity. Ischemic heart disease, cirrhosis, major
      hepatectomy, and RBC transfusion were independent risk factors for postoperative
      mortality. Age did not result an independent factor related to mortality and
      severe morbidity. Two different scores were developed and have proved to be
      statistically related with severe morbidity and mortality. Moreover, in patients
      with score >=2, severe morbidity increased from 24.2% in YP, to 29.3% in EP, and
      to 40.0% in VEP, P = .047. Likewise, mortality increased from 2.3% in YP, to 7.0%
      in EP, and to 22.7% in VEP, in patients with score >=2, P = .017.Age alone should
      not be considered a contraindication for hepatectomy. We identified factors and
      proposed 2 scores that can be useful to stratify the risk of morbidity and
      mortality after hepatectomy. Moreover, severe morbidity and mortality increases
      according to the different age intervals in patients with scores >=2.

PMID- 28514318
TI  - Cerebral Oxygen Saturation in Children With Congenital Heart Disease and Chronic
      Hypoxemia.
AB  - BACKGROUND: Increased hemoglobin (Hb) concentration accompanying hypoxemia is a
      compensatory response to maintain tissue oxygen delivery. Near infrared
      spectroscopy (NIRS) is used clinically to detect abnormalities in the balance of
      cerebral tissue oxygen delivery and consumption, including in children with
      congenital heart disease (CHD). Although NIRS-measured cerebral tissue O2
      saturation (ScO2) correlates with arterial oxygen saturation (SaO2), jugular bulb
      O2 saturation (SjbO2), and Hb, little data exist on the interplay between these
      factors and cerebral O2 extraction (COE). This study investigated the
      associations of ScO2 and DeltaSaO2-ScO2 with SaO2 and Hb and verified the normal
      range of ScO2 in children with CHD. METHODS: Children undergoing cardiac
      catheterization for CHD were enrolled in a calibration and validation study of
      the FORE-SIGHT NIRS monitor. Two pairs of simultaneous arterial and jugular bulb
      samples were drawn for co-oximetry, calculation of a reference ScO2 (REF CX), and
      estimation of COE. Pearson correlation and linear regression were used to
      determine relationships between O2 saturation parameters and Hb. Data were also
      analyzed according to diagnostic group defined as acyanotic (SaO2 >= 90%) and
      cyanotic (SaO2 < 90%). RESULTS: Of 65 children studied, acceptable jugular bulb
      samples (SjbO2 absolute difference between samples <=10%) were obtained in 57
      (88%). The DeltaSaO2-SjbO2, DeltaSaO2-ScO2, and DeltaSaO2-REF CX were positively
      correlated with SaO2 and negatively correlated with Hb (all P < .001). Although
      by diagnostic group ScO2 differed statistically (P = .002), values in the
      cyanotic patients were within the range considered normal (69% +/- 6%). COE
      estimated by the difference between arterial and jugular bulb O2 content
      (DeltaCaO2-CjbO2, mL O2/100 mL) was not different for cyanotic and acyanotic
      patients (P = .10), but estimates using DeltaSaO2-SjbO2, DeltaSaO2-ScO2, or
      DeltaSaO2-ScO2/SaO2 were significantly different between the cyanotic and
      acyanotic children (P < .001). CONCLUSIONS: Children with adequately compensated
      chronic hypoxemia appear to have ScO2 values within the normal range. The
      DeltaSaO2-ScO2 is inversely related to Hb, with the implication that in the
      presence of reduced Hb, particularly if coupled with a decreased cardiac output,
      the ScO2 can fall to values associated with brain injury in laboratory studies.

PMID- 28514319
TI  - Prospective External Validation of Three Preoperative Risk Scores for Prediction
      of New Onset Atrial Fibrillation After Cardiac Surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with early and
      late morbidity and mortality of cardiac surgical patients. Prophylactic treatment
      of atrial fibrillation (AF) has been recommended to improve outcome in cardiac
      surgical patients at high risk of developing POAF. Reliable models for prediction
      of POAF are needed to achieve that goal. This study attempted to externally
      validate 3 risk models proposed for preoperative prediction of POAF in cardiac
      surgical patients: the POAF score, the CHA2DS2-VASc score, and the Atrial
      Fibrillation Risk Index. METHODS: This was a prospective cohort study of 1416
      adult patients who underwent nonemergent coronary artery bypass graft and/or
      valve surgery in a single cardiac surgical center between February 2014 and
      September 2015. A risk score for each of the 3 prediction models was calculated
      in each patient. All patients were followed for up to 2 weeks, or until hospital
      discharge, to observe the primary outcome of new onset AF requiring treatment.
      Discrimination was assessed using receiver operating characteristic curves.
      Calibration was assessed using the Pearson chi goodness-of-fit test and
      calibration plots. Utility of the score to implement AF prophylaxis based on the
      risk of POAF, in comparison to strategies of treating all patients, or not
      treating any patients, was assessed via a net benefit analysis. RESULTS: Of the
      1416 patients included in this study, 478 had the primary outcome (33.8%). The
      areas under the receiver operating characteristic curve for prediction of POAF in
      the population subsets for which the scores were validated were as follows: 0.651
      (95% confidence interval [CI], 0.621-0.681) for the POAF score, 0.593 (95% CI,
      0.557-0.629) for the CHA2DS2-VASc score (P < .001 versus POAF score, P < .222
      versus Atrial Fibrillation Risk Index), and 0.563 (95% CI, 0.522-0.604) for the
      Atrial Fibrillation Risk Index (P < .001 versus POAF score). The calibration
      analysis showed that the predictive models had a poor fit between the observed
      and expected rates of POAF. Net benefit analysis showed that AF preventive
      strategies based on these scores, and targeting patients with moderate or high
      risk of POAF, improve decision-making in comparison to preventive strategies of
      treating all patients. CONCLUSIONS: The 3 prediction scores evaluated in this
      study have limited ability to predict POAF in cardiac surgical patients. Despite
      this, they may be useful in preventive strategies targeting patients with
      moderate or high risk of PAOF in comparison with preventive strategies applied to
      all patients.

PMID- 28514320
TI  - Preoperative Warming Versus no Preoperative Warming for Maintenance of
      Normothermia in Women Receiving Intrathecal Morphine for Cesarean Delivery: A
      Single-Blinded, Randomized Controlled Trial.
AB  - BACKGROUND: Rates of hypothermia for women undergoing spinal anesthesia for
      cesarean delivery are high and prevention is desirable. This trial compared the
      effectiveness of preoperative warming versus usual care among women receiving
      intrathecal morphine, which is thought to exacerbate perioperative heat loss.
      METHODS: A prospective, single-blinded, randomized controlled trial compared 20
      minutes of forced air warming (plus intravenous fluid warming) versus no active
      preoperative warming (plus intravenous fluid warming) in 50 healthy American
      Society of Anesthesiologists graded II women receiving intrathecal morphine as
      part of spinal anesthesia for elective cesarean delivery. The primary outcome of
      maternal temperature change was assessed via aural canal and bladder temperature
      measurements at regular intervals. Secondary outcomes included maternal thermal
      comfort, shivering, mean arterial pressure, agreement between aural temperature,
      and neonatal outcomes (axillary temperature at birth, Apgar scores,
      breastfeeding, and skin-to-skin contact). The intention-to-treat population was
      analyzed with descriptive statistics, general linear model analysis, linear mixed
      model analysis, chi test of independence, Mann-Whitney, and Bland-Altman
      analysis. Full ethical approval was obtained, and the study was registered on the
      Australia and New Zealand Clinical Trials Registry (Trial No: 367160, registered
      at http://www.ANZCTR.org.au/). RESULTS: Intention-to-treat analysis (n = 50)
      revealed no significant difference in aural temperature change from baseline to
      the end of the procedure between groups: F (1, 47) = 1.2, P = .28. There were no
      other statistically significant differences between groups in any of the
      secondary outcomes. CONCLUSIONS: A short period of preoperative warming is not
      effective in preventing intraoperative temperature decline for women receiving
      intrathecal morphine. A combination of preoperative and intraoperative warming
      modalities may be required for this population.

PMID- 28514321
TI  - Patient Blood Management in Major Orthopedic Surgery: Less Erythropoietin and
      More Iron?
AB  - Erythropoietin (EPO) is proposed preoperatively to reduce blood transfusion in
      anemic patients (hemoglobin < 13 g/dL) scheduled for a major orthopedic surgery.
      New intravenous iron formulations allow infusion of higher doses, increasing EPO
      response. In that context, we evaluated in a before-after study (n = 62 and 65
      patients for each period) a new EPO administration protocol (2 injections 4 and 3
      weeks before surgery, and a third if hemoglobin <13 g/dL instead of <15 g/dL 2
      weeks before surgery). After this protocol implementation, the mean (standard
      deviation) number of EPO injections decreased from 2.8 (0.5) to 2.2 (0.4)/patient
      (P < .0001) without changing transfusion rates (3% in the 2 periods).

PMID- 28514322
TI  - Relationship Between a Sepsis Intervention Bundle and In-Hospital Mortality Among
      Hospitalized Patients: A Retrospective Analysis of Real-World Data.
AB  - BACKGROUND: Sepsis is a systemic response to infection that can lead to tissue
      damage, organ failure, and death. Efforts have been made to develop evidence
      based intervention bundles to identify and manage sepsis early in the course of
      the disease to decrease sepsis-related morbidity and mortality. We evaluated the
      relationship between a minimally invasive sepsis intervention bundle and in
      hospital mortality using robust methods for observational data. METHODS: We
      performed a retrospective cohort study at the University of California, San
      Francisco, Medical Center among adult patients discharged between January 1,
      2012, and December 31, 2014, and who received a diagnosis of severe sepsis/septic
      shock (SS/SS). Sepsis intervention bundle elements included measurement of blood
      lactate; drawing of blood cultures before starting antibiotics; initiation of
      broad spectrum antibiotics within 3 hours of sepsis presentation in the emergency
      department or 1 hour of presentation on an inpatient unit; administration of
      intravenous fluid bolus if the patient was hypotensive or had a lactate level >4
      mmol/L; and starting intravenous vasopressors if the patient remained hypotensive
      after fluid bolus administration. Poisson regression for a binary outcome
      variable was used to estimate an adjusted incidence-rate ratio (IRR) comparing
      mortality in groups defined by bundle compliance measured as a binary predictor,
      and to estimate an adjusted number needed to treat (NNT). RESULTS: Complete
      bundle compliance was associated with a 31% lower risk of mortality (adjusted
      IRR, 0.69, 95% confidence interval [CI], 0.53-0.91), adjusting for SS/SS
      presentation in the emergency department, SS/SS present on admission (POA), age,
      admission severity of illness and risk of mortality, Medicaid/Medicare payor
      status, immunocompromised host status, and congestive heart failure POA. The
      adjusted NNT to save one life was 15 (CI, 8-69). Other factors independently
      associated with mortality included SS/SS POA (adjusted IRR, 0.55; CI, 0.32-0.92)
      and increased age (adjusted IRR, 1.13 per 10-year increase in age; CI, 1.03
      1.24). CONCLUSIONS: The University of California, San Francisco, sepsis bundle
      was associated with a decreased risk of in-hospital mortality across hospital
      units after robust control for confounders and risk adjustment. The adjusted NNT
      provides a reasonable and achievable goal to observe measureable improvements in
      outcomes for patients diagnosed with SS/SS.

PMID- 28514323
TI  - Perioperative Care of the Concussed Patient: Making the Case for Defining Best
      Anesthesia Care.

PMID- 28514324
TI  - Use of the Fluid Challenge in Critically Ill Adult Patients: A Systematic Review.
AB  - The fluid challenge (FC) aims at identifying patients in whom fluid
      administration improves hemodynamics. Although the FC has been extensively
      studied, the implementation and definition of improvement are not standardized.
      This systematic review of studies published between January 1, 1994 and December
      31, 2014 characterizes these key components of the FC for critically ill adult
      patients, as described in the medical literature in the last 20 years. A
      literature search was performed using MEDLINE, Embase, and Cochrane. For each
      study, data were collected on study design, study size, study setting, patient
      population, and how the FC was administered. Eligibility criteria for FC were (1)
      the infusion of a definite quantity of fluid, (2) of a specific type, (3) in a
      fixed time period (expressed as either span or infusion rate), (4) with a defined
      hemodynamic variable as the target, and (5) for a predetermined threshold. One
      hundred fifty-seven full-text manuscripts were extracted from 870 potentially
      relevant studies. The inclusion criteria were met by 71 studies including 3617
      patients. Sixty-six studies were from a single center and 45 were prospective
      observational in format. The most common amount infused was 500 cc, used by 55
      (77.5%) studies. The most commonly infused fluids were colloids (62.0%). In 43
      (60.5%) studies, the FC was administered between 20 and 30 minutes. A positive
      response to fluid administration was defined as an increase >=15% of cardiac
      index or cardiac output in 44 (62.6%) studies. Static or dynamic physiologic
      indices were utilized in a minority of studies (16.9%) and safety limits for
      interrupting the FC are adopted in 4 (5.6%) studies only. This systematic review
      indicates that the FC most commonly consists in infusing 500 mL of crystalloids
      or colloids in 20-30 minutes, and considered an increase in cardiac index >=15%
      as a positive response. However, definite standards for FC administration and
      evaluation remain undefined.

PMID- 28514325
TI  - An Etomidate Analogue With Less Adrenocortical Suppression, Stable Hemodynamics,
      and Improved Behavioral Recovery in Rats.
AB  - BACKGROUND: ET-26 hydrochloride (ET-26HCl) is a novel etomidate analogue designed
      to alleviate the adrenocortical suppression caused by etomidate while retaining
      the rapid sedative-hypnotic onset and stable hemodynamic features of etomidate.
      This study compared the anesthetic effect, hemodynamic stability, and recovery
      profiles of ET-26HCl, etomidate, and the sedative-hypnotic drug propofol in rats.
      METHODS: The metabolic half-life of ET-26HCl was determined in vitro using high
      performance liquid chromatography analysis of samples of rat plasma and liver
      homogenates taken from 3 animals. Hypnotic median effective doses (HD50) of ET
      26HCl, etomidate, and propofol were determined by up-and-down methods. Anesthesia
      effect and mean arterial pressure were estimated using equivalent intravenous
      (IV) doses of propofol, etomidate, and ET-26HCl in the rats. Serum concentrations
      of corticosterone were analyzed by enzyme-linked immunosorbent assay. The ability
      of rats to recover from the sedative-hypnotic effects of the drugs was evaluated
      using open field and Morris water maze tests at equipotent doses of propofol,
      etomidate, ET-26HCl, and normal saline. RESULTS: The metabolic half-life of ET
      26HCl was 81 +/- 6 minutes in rat plasma and 126 +/- 12 minutes in incubation
      liver homogenate (mean +/- standard deviation), respectively. In vivo experiments
      showed that the potency of ET-26HCl to cause a loss of righting reflex in rats
      was 3 times lower than that of etomidate in the rats. IV propofol caused a
      greater decrease in mean arterial pressure relative to the baseline (-27.9 mm Hg)
      than did ET-26HCl (-10.7 mm Hg) and etomidate (-19.4 mm Hg) at equipotent doses.
      Serum corticosterone levels after drug administration were significantly higher
      in the ET-26HCl group than in the etomidate group at equivalent doses when
      measured 15 (P < .001), 30 (P < .001), and 60 (P = .002) minutes after
      stimulation with adrenocorticotropic hormone (ACTH1-24). Recovery of spatial
      orientation from anesthesia induced by an IV bolus injection was faster with ET
      26HCl than with propofol, but recovery of spontaneous activity was slower.
      CONCLUSIONS: ET-26HCl has anesthetic potency and hemodynamic stability similar to
      etomidate, but it caused less adrenocortical hormone synthesis suppression than
      etomidate and faster spatial orientation recovery from anesthesia than propofol,
      which was similar to etomidate.

PMID- 28514326
TI  - Cancellation of Elective Cases in a Recently Opened, Tertiary/Quaternary-Level
      Hospital in the Middle East.
AB  - Case cancellations have a negative financial impact due to revenue loss and the
      potential costs of underutilized time. The goals of this study at a recently
      opened hospital in the Middle East were to measure the cancellation rates for
      elective surgical or endoscopic cases and to identify the reasons for
      cancellation. During the 1-month study period, 170 (22.4%) of the 760 scheduled
      cases were cancelled. Cultural norms and patient no-shows on the day of surgery
      accounted for the majority of case cancellations. Understanding local factors on
      hospital functions may be vital for organizations expanding into new geographic
      areas.

PMID- 28514328
TI  - [An aging brain: morphofunctional aspects].
AB  - A review of main results in the field that are relevant for understanding of the
      clinical pathology developed in old age is presented. The authors focus attention
      on the characteristics of atrophic processes and their severity in different
      brain structures including cognitive impairment (memory etc). Correlations
      between structural changes in brain tissues and neurochemical and bioelectrical
      processes in the CNS are discussed.

PMID- 28514327
TI  - Postoperative Assessment of Myocardial Function and Microcirculation in Patients
      with Acute Coronary Syndrome by Myocardial Contrast Echocardiography.
AB  - BACKGROUND Postoperative myocardial function and microcirculation of acute
      coronary syndrome (ACS) was assessed by myocardial contrast echocardiography
      (MCE). MATERIAL AND METHODS Eighty-nine ACS patients treated with percutaneous
      coronary intervention (PCI) were detected by MCE and two-dimensional
      ultrasonography before and a month later after PCI respectively. Their myocardial
      perfusion was evaluated by myocardial contrast score (MSC) and contrast score
      index (CSI); cross-sectional area of microvessel (A), average myocardial
      microvascular impairment (beta), and myocardial blood flow (MBF) were analyzed by
      cardiac ultrasound quantitative analysis (CUSQ), and fractional flow reserve
      (FFR) change was observed. Left ventricular ejection fraction (LVEF), left
      ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic
      dimension (LVESD) were observed; the index of microcirculatory resistance (IMR),
      FFR, and coronary flow reserve (CFR) were detected to evaluate coronary
      microcirculation. RESULTS None of the 89 patients experienced no-reflow. Patients
      with normal myocardial perfusion mostly had normal or slightly decreased
      ventricular wall motion after PCI. A month after the operation, there was an
      increase in A, beta, MBF, LVEF, E/A, IMR, FFR, and CFR (all P<0.05), while LVEDD,
      LVESD, diastolic gallop A peak, E/Ea, E/Ea*S, and Tei decreased (all P<0.05).
      LVEF and IMR were in positive correlations with A. LVEF, IMR, FFR and CFR were
      positively correlated with b and MBF (both r>0, P<0.05), while E/Ea*Sa and Tei
      were negatively correlated with b and MBF (r<0, P<0.05). CONCLUSIONS MCE can
      safely assess post-PCI myocardial function and microcirculation of ASC.

PMID- 28514329
TI  - [Brain plasticity: limitations and possibilities].
AB  - Biological limitations related to the brain regeneration and stem cells
      transplantation as well as the factors influencing the brain plasticity following
      the brain injury, including epigenetic regulatory mechanisms, are presented. Non
      invasive transcranial microelectrostimulation is considered as a perspective
      method of polysystemic influence on endogenic mechanisms of brain recovery.

PMID- 28514330
TI  - [MRI morphometry of neuroplastic changes in the brain after conservative
      treatment of traumatic brachial plexopathy].
AB  - AIM: To identify neuroplastic changes in the brain structures during treatment of
      traumatic axonotomy of the brachial plexus (the pathology of peripheral nervous
      system). MATERIAL AND METHODS: MRI morphometry of white and grey matter was
      studied in 62 patients with traumatic axonotomy of the brachial plexus. RESULTS:
      There were correlations between the thickness of sensorimotor cortex,
      morphometric parameters (volume, diffusion, fractional anisotropy) of subcortical
      formations (corticospinal tracts, the forceps minor), severity of neurological
      deficit and dynamics of clinical course depending on the therapeutic strategy.
      CONCLUSION: The results expand the current view on central mechanisms of
      posttraumatic axon regeneration on the model of traumatic brachial plexopathy and
      establish a neuromodulative effect of neuromidin and noofen. Some morphometric
      parameters may be used as the markers of reactive neuroplastic processes in the
      central nervous system.

PMID- 28514331
TI  - [Diagnosis and treatment of migraine: Recommendations of the Russian experts].
AB  - These recommendations on the diagnosis and treatment of migraine were elaborated
      by Russian headache experts in accordance with the evidence-based practice.
      Together with the latest classification, diagnostic principles and criteria of
      different clinical sub-forms the consensus contains basic data on migraine
      epidemiology, pathophysiological mechanisms, differential diagnosis and most
      effective and evidence based approaches to pharmacological and non
      pharmacological management of migraine patients.

PMID- 28514332
TI  - [Clinical significance of nausea in migraine].
AB  - AIM: To study the prevalence and intensity of nausea in pain, prodromal and
      postdromal phases of migraine paroxysm, and in between the paroxysms in migraine
      patients, depending on the type of migraine paroxysm and frequency of pain days,
      and to evaluate an effect of nausea on the course of migraine. MATERIAL AND
      METHODS: One hundred and four patients with migraine, aged from 18 to 60 years,
      were examined. The intensity of nausea was evaluated by a 5-point verbal analogue
      scale, and its intensity in between the paroxysms by the Gastrointestinal Symptom
      Rating Scale. All of the patients underwent a complex examination of the
      gastrointestinal tract. RESULTS AND CONCLUSION: Paroxysms with accompanying
      nausea were found in 90% patients. Acute nausea was associated with older age,
      earlier onset and longer experience of migraine. In a group of patients with
      acute nausea, the frequency and intensity of migraine paroxysms, probability of
      reoccuring pain in the first day and the severity of social disability were
      higher. Development of nausea in between the paroxysms and its intensity was
      significantly higher in patients with high intensity of nausea in migraine
      paroxysms. Nausea in the prodrome was significantly associated with migraine
      without aura and chronicity of the disorder. Patients with nausea in the prodrome
      also had a longer painful phase and more severe social disability. No
      relationship between organic diseases of the digestive tract and nausea was
      found. Nausea can have its own pathological mechanisms not related to concomitant
      diseases of the digestive tract that should be taken into account in therapeutic
      interventions aimed at improving quality of life of the patients.

PMID- 28514333
TI  - [Diagnosis of refractory forms of chronic primary headache].
AB  - A number of patients with primary headaches remain insensitive or refractory to
      treatment despite correctly selected drugs, adequate therapeutic dose and
      duration of therapy. The importance of refractory problem is determined by the
      fact that patients are completely maladjusted, disabled, and keeping these
      patients is very difficult even for seasoned professionals. Determination of the
      correct tactics and success of the treatment depends, in the first place, on the
      correct diagnosis. This article discusses the diagnostic criteria for the most
      important forms such as refractory chronic migraine or refractory chronic cluster
      headache presented by experts of the European Headache Federation in two separate
      Consensus.

PMID- 28514334
TI  - [Anxiety and depressive disorders in Parkinson's disease].
AB  - This review presents the most recent data of worldwide research on anxiety and
      depressive disorders in patients with Parkinson's disease. Their characteristics
      and epidemiology, pathogenetic and clinical features, methods of diagnosis and
      treatment are presented. Depression occurs in 40-50% of patients with PD, anxiety
      in 17-43% of patients. Pramipexole, a dopamine agonist, is only one drug
      recommended for depression treatment. Nortriptyline and desipramine, belonging to
      the group of tricyclic antidepressants (TCAs), are considered to be possibly
      effective. There are no clear recommendations for treatment of anxiety. In
      general, methods of therapy of anxiety and depressive disorders in PD are not
      well understood which determines the conduct of large-scale studies in the
      future.

PMID- 28514335
TI  - [The quality of medical care and cooperation of patients with amyotrophic lateral
      sclerosis in the Russian Federation].
AB  - The quality of medical care for patients with amyotrophic lateral sclerosis (ALS)
      in the Russian Federation is analyzed taking into account the cooperation of
      patients. Two hundred and fifty-one patients with ALS were observed. Ninety-nine
      patients, including 16 who were followed up, were examined. Other patients
      (n=152) were consulted indirectly including 28 followed up. It has been shown
      that 79,8% of the patients are characterized by the low level of cooperation with
      neurologists regardless of the quality of medical care; 8.3% of patients are
      managed in facilities (or by physicians), which don't use the International
      standard of ALS management. Only 11.9% of patients receive medical care in
      accordance with this standard and in these cases, the high level of cooperation
      of the patients with medical services was recorded. A dual system that combines
      the services provided by medical insurance, private treatment facilities, charity
      organizations, structures of medical/social care with different levels of
      availability and methods of consumer-provider interactions is the most effective.

PMID- 28514336
TI  - [The quality of life in patients with a different types of myasthenia gravis].
AB  - AIM: Researching quality of life in patients with myasthenia gravis at different
      clinical variants of disease. MATERIAL AND METHODS: We studied 103 patients with
      myasthenia gravis. A battery of tests and scales for assessment of neurological
      deficit and quality of life was used. RESULTS AND CONCLUSION: Two types of
      disease have been identified in myasthenia gravis: favorable and unfavorable. The
      minimal duration of disease before thymectomy is the main determinant of the best
      outcome. Favorable clinical type of myasthenia gravis was found in patients with
      weakness in extraocular and limb muscles. Factors associated with a poor quality
      of life included following: weakness in bulbar and respiratory muscles (p<0.003),
      endocrine comorbidities (p<0.01) or thymoma (p<0.005).

PMID- 28514337
TI  - [Sex differences in acute disturbances of cerebral blood circulation].
AB  - It is shown that in the development of stroke observed sex differences, which
      manifest themselves both clinically and by laboratory parameters. While men have
      a higher incidence of stroke for most of his life, a woman in a more advanced age
      have a higher risk for stroke. Sex differences in the development of stroke
      depend on several factors, including genetic and hormonal changes throughout
      life. Studies sex differences in the risk of stroke is only in the initial stage,
      but the first results show that there are differences in neuronal cell death in
      males and females after experimental ischemic stroke. A better understanding of
      the mechanisms underlying the development of stroke in men and women will lead to
      more appropriate treatment strategies for patients of both sexes.

PMID- 28514338
TI  - [A comparative chemoreactome analysis of mexidol].
AB  - AIM: To compare mexidol with control molecules (choline alfoscerate, piracetam,
      glycine, semax) using chemoreactome analysis. MATERIAL AND METHODS: The chemical
      structure of mexidol was compared to molecule metabolites extracted from the
      Human Metabolome Database (HMDB) and a drug database. More than 40 000 of
      metabolites from HMDB were used as a model of human metabolome. RESULTS AND
      CONCLUSION: The chemoreactome analysis showed that mexidol may be (1) an agonist
      of acetylcholine and GABA-A receptors; (2) an anti-inflammatory agent, the
      effects of which are carried out by inhibiting the synthesis of pro-inflammatory
      prostaglandins; (3) a neurotrophic agent with neuroprotective properties; (4) a
      coagulation inhibitor; (5) a diabetes medication and (6) a hypolipidemic agent.
      Compared to 'control' molecules, mexidol has a more pronounced safety profile (a
      lower impact on serotonin, dopamine and adrenergic receptors, a lesser degree of
      interaction with the potassium channels of the heart, MAO and P450 cytochromes).
      The results of modeling allow to specify the mechanisms of action of mexidol at
      the molecular level.

PMID- 28514339
TI  - [Increased oral fluid remineraling function by endogenous and exogenous
      saturation methods of its mineral complexes].
AB  - RELEVANCE: One of the most common problems in modern caries prevention is the
      development of techniques to increase tooth resistance to the effects of
      cariogenic factors. Therefore, research is needed to study the chemical
      composition of tissues like teeth and body fluids surrounding the tooth to
      prevent demineralization process. The purpose of determining the effectiveness of
      work- and correlation relationship between endo saturation exogenous methods oral
      liquid mineral complexes. MATERIAL AND METHODS: In 95 patients analyzed the
      chemical composition and structure of the oral fluid by IR spectroscopy. For the
      collection of IR spectra used Verteh-70 spectrometer ('Bruker', Germany) and the
      prefix of frustrated total internal reflection PLATINUM ATR diamond prism.
      RESULTS AND DISCUSSION: A correlation between the use of endogenous and exogenous
      methods of caries prevention, in favor of the former, as well as changes in the
      mineral-organic and phosphate-carbon ratio in the dry residues of oral fluid.

PMID- 28514340
TI  - [The impact of surgical and conservative treatment of periodontal disease on
      structural and functional condition of major blood vessels].
AB  - The study included 55 patients (24 men and 31 women aged 30-70 years) with
      chronic periodontal disease and atherosclerosis of brachiocephalic arteries
      (BCA). Patients in group 1 received only conservative treatment for periodontal
      disease, while in group 2 both conservative and surgical treatment were
      performed. The values were evaluated at baseline and 6 months after treatment.
      Capillaroscopy and laser Doppler flowmetry showed an improvement in periodontal
      regional vascular network. The level of IL-6 decreased by 3.7 pg/ml and 5.9
      pg/ml, C-reactive protein - by 2.0 mg/l and 3.4 mg/l in groups 1 and 2
      correspondingly. Dark-field microscopy showed the decrease in the thickness of
      perfused boundary region by 0.05 mm and 0.28 mm, and the increase of red blood
      cells filling by 1.2% and 7.8% correspondingly. According to the results of
      ultrasound scanning of BCA after 6 months the number of atherosclerotic plaques
      and lumen of the vessels in the area of the plaques has not changed. BCA tone has
      not changed in group 1 and increased by 1-2% in group 2. Intima-media complex
      thickness decreased in group 1 by 0.02-0.03 mm, in group 2 - by 0.04 mm. The
      obtained data prove correlation of vascular status of periodontal and major blood
      vessels.

PMID- 28514341
TI  - [Endodontic treatment efficacy enhancement by means of instrumental
      physiotherapy].
AB  - The article describes in detail and examines the prospects of such methods as
      electroodontodiagnosis, diathermocoagulation and apex-phoresis. It proves the
      necessity of development and standardization of devices for the mentioned
      treatment modalities that will improve the effectiveness an quality of caries
      complications treatment.

PMID- 28514342
TI  - [Evaluation of main and additional root canal curvature in maxillary molars].
AB  - The aim of the study was to investigate the degree of the main and additional
      root canal curvatures of the maxillary molars in Krasnoyarsk population. Main and
      additional root canal curvature was measured in 48 maxillary first molars (M1)
      and 122 second molars (M2) with cone beam computer tomography. In total 476
      measurements were taken for M1 and 1038 for M2 (all measurements were doubled in
      sagittal and coronal views). M2 showed more variety of root canal morphology and
      significantly higher proportion of additional root canals. Curvature rates of M1
      did not differ significantly from M2. Additional root canals had close or similar
      curvature rates with the main ones. The obtained data are useful for the
      improvement of root canal treatment efficacy and endodontic treatment planning.

PMID- 28514343
TI  - [Effect of dexmedetomidine on perfusion of free flaps transferred to head and
      neck].
AB  - The paper presents the impact of perioperative care on feasibility of free fibula
      flap transfer for facial reconstruction. Flaps vitality was measured by means of
      somatic oximetry in 85 patients aged 20-74 years receiving reconstruction
      procedures in midfacial and lower facial areas. The patients were divided in
      three groups according to sedation agent used postoperatively. It has been
      demonstrated that dexmedetomidine postoperative sedation significantly improved
      free fibula flaps perfusion compared to propofol sedation.

PMID- 28514344
TI  - [Erbium laser application for oral surgery in patients with platelet hemostatic
      disorders].
AB  - Hemostatic disorders are typically associated with prolonged bleeding after or
      during surgical procedures. The aim of the study was to increase the efficiency
      of oral surgery in these patients using erbium laser. Selected 46 patients
      receiving oral surgery were randomly divided in 2 groups: 43 patients with
      thrombocytopenia, trombocytemia and other platelet disorders treated with erbium
      laser and a control group of 43 patients without concomitant pathology determined
      for conventional surgical treatment. No postoperative bleeding was seen in group
      1. Conventional procedures were associated with significantly more postoperative
      pain and epithelization took 1-3 days longer. Erbium laser radiation is an up-to
      date method which can be successfully used for oral surgery in patients with
      hemostatic disorders.

PMID- 28514345
TI  - [Immunohistochemical criteria for differential diagnostics of squamous epithelium
      changes in pyogenic granuloma and squamous cell carcinoma of the oral mucosa].
AB  - The paper presents an example of differential diagnostic studies for pyogenic
      granuloma and oral squamous cell carcinoma (SCC). In the described case
      immunohistochemistry with antibodies to Ki-67 and Gli1 was used as conventional
      histological procedure proved to be inconvenient for adequate diagnostics. The
      immunohistochemical study established increased proliferative activity of
      epithelial cells specific both pyogenic granuloma and oral SCC, but intensive
      Gli1 protein expression in membranes and cytoplasm of epithelial cells with
      malignant transformation allowed differentiation of these neoplasms.

PMID- 28514346
TI  - [Systemic toxicity of local anesthetics].
AB  - The paper presents characteristics of local anesthetics used in dentistry and
      maxillofacial surgery taking into account their effectiveness and toxicity. We
      described the main clinical symptoms of manifestation of systemic toxicity and
      measures for prevention of local anesthesia complications, as well as the
      detailed protocol of 'lipid rescue' and resuscitation at manifestation of
      systemic toxic reaction of local anesthetics with the mechanism of the fatty
      emulsion action.

PMID- 28514347
TI  - [Clinical and diagnostic rationale for the final stage of orthodontic treatment].
AB  - The aim of the study was to improve the efficiency of the final stage of
      orthodontic treatment. The study included 32 patients divided into two groups of
      16. Orthodontic treatment was performed using a bracket system active self
      ligation straight arc technique with step adjustment anthropometric quantitative
      evaluation system (The ABO Model Grading System). Centric occlusion and centric
      relation were analyzed at baseline and after treatment by mandible position
      indicator MPI (Mandibular Position Indicator). The first group received treatment
      according to conventional protocol, in the second group braces were readjusted by
      indirect bonding after ABO anthropometric measurements. The efficiency of
      orthodontic treatment using ABO system at the late stages of adjustment in the
      second group was significantly higher than in the first group (p=0.002248;
      p=0.023431, respectively). MPI analysis in the first group in 10 (62.5%) patients
      showed mismatch of centric occlusion and centric relation not seen in the second
      group. In 3 (18.75%) patients of group 2 the difference did not exceed 0.5 mm
      which was considered normal. Thus, the application of ABO anthropometric system
      followed by readjustment of incorrectly positioned brackets by indirect bonding
      promotes MPI values improvement, which in turn allows getting the most accurate,
      and stable results of orthodontic treatment.

PMID- 28514348
TI  - [Dynamics of immunological features of oral liquid in children with chronic
      catarrhal gingivitis living on polluted territories with fluoride and iodine
      deficiency].
AB  - The aim of the study was to assess the state of oral liquid (OL) immunity in
      children with chronic catarrhal gingivitis (CCG) living in adverse environmental
      conditions. 120 children aged 7-15 residing in ecologically unfavorable areas of
      Lviv region were examined, while 75 children living in 'relatively clean' region
      were involved in the control group. Chronic catarrhal gingivitis was diagnosed
      according to Danilevskiy classification (1994). The level of cytokines in oral
      liquid of 7-years-old children living in ecologically polluted region (EPR), was
      (198.19+/-4.11).106/l, which was 1.4 times more than in the conditionally clean
      region (CCR): (141.09+/-4.10).106/l (p<0.01). Analysis of cytokine profile in 7
      years-old from EPR showed increased levels of IL-6 proinflammatory cytokines by
      11.22% (13.78+/-0.38 pg/ml vs 12.39+/-0.50 pg/ml in controls, p<0.05) and the
      decrease of IL-4 anti-inflammatory cytokine by 26.9% (7.12+/-0.62 pg/ml vs 9.74+/
      0.58 pg/ml, p<0.01). In 12 years-old from EPR quantity of leukocytes in OL was
      1.3 times higher than in controls ((246.81+/-4.16).106/l vs (190.02+/
      4.11).106/l, p<0.01), the increase of the IL-6 content of 27.1% (p<0.01) and
      reduce of the IL-4 of 21.5% (p<0.05) compared to controls was also seen. At the
      age of 15 further increase of leucocytes in children from EPR was revealed:
      (297.53+/-4.15).106/l, which was 1.2 times higher than in controls (p<0.01).
      Changes of cytokine profile in this age group were characterized by increased
      content of IL-6 of 26.41% (p<0.05) and IL-4 drop of 28.53% (p>0.05). Thus the age
      dependent trend for the increase of leukocytes count in OL and pro-inflammatory
      cytokine IL-6 with the decrease of anti-inflammatory cytokine IL-4 is noted in
      children with CCG living in EPR.

PMID- 28514349
TI  - [Elastic properties and porosity of dental blocks made from non-metal materials
      used for chairside CAD/CAM crowns].
AB  - Elastic properties and internal structure of glass-ceramic, feldspatic ceramic,
      PMMA and hybrid blocks for chairside CAD/CAM dental crowns were assessed by
      pulsed acoustic microscopy. Elastic modulus of hybrid ceramic was 1.5 times
      inferior to feldspatic ceramic and glass-ceramic but almost 10 times higher than
      those of polymer samples. We found the presence of pores from a few to hundreds
      of microns in the bulk of inorganic materials samples, isolated point defects
      were revealed in polymer materials while in hybrid material defects were not
      found.

PMID- 28514350
TI  - [Improvement of training quality in continuous medial education of dentists and
      maxillofacial surgeons].
AB  - The new concept of continuous medical education is based on individual learning
      paths of each specialist in conjunction with the use of modern educational
      technologies, including IT. The aim of this study was to undertake a review of
      modern methods of health care professionals training in the framework of
      continuous medical education profile introduced by the Ministry of Health. The
      paper presents the best IT practices of Central Research Institute of Dentistry
      and Maxillofacial Surgery in the training of dentists and maxillofacial surgeons
      aimed for the modernization of medical education.

PMID- 28514351
TI  - [Essential questions of training of dentists for accreditation].
AB  - The paper presents sociological study aimed to analyze the conditions and
      methodological rationale for the basic directions of optimization of
      accreditation procedure for dentists. The study included 129 graduates of dental
      faculties of educational institutions of Sechenov First Moscow State Medical
      University. The material was collected by questionnaire survey and interviewing.
      The obtained results show that the introduced system of professionals'
      accreditation is an innovative educational technology allowing objectively assess
      the level of theoretical and practical training of dentists. Much of its
      effectiveness depends on the quality of produced and updated on a timely basis
      uniform base of assessment tools, the selection of the most prepared members for
      the accreditation commissions and creation of adequate conditions for its
      implementation in educational and scientific organizations.

PMID- 28514352
TI  - [Synthetic osteoplastic materials for alveolar bone augmentation before dental
      implantation].
AB  - The study presents scientific data about surgical preparation of the alveolar
      bone before dental implantation by applying synthetic osteoplastic materials. The
      review analyzed the results of experimental and clinical studies on structural
      features and the efficiency of these materials, the time for replacement of new
      formed bone tissue and contains comparative analysis of the efficiency of
      synthetic bone substitutes and other types of osteoplastic materials.

PMID- 28514353
TI  - [Mantle dentin as biomodel of materials for structural teeth restoration].
AB  - The article describes a structural element of natural teeth - mantle dentin. It
      has been shown that the presence of this element in the structure of a natural
      tooth largely ensures its strength under the influence of repeated loads in a
      functional oral environment and arrests crack growth at the enamel/dentine
      interface. This later effect is explained by the influence of a thin layer of
      mantle dentine, which has physical and mechanical characteristics different from
      that of the main dentin.

PMID- 28514354
TI  - [Out-patient dental care in patients with arterial hypertension].
AB  - The aim of the study was to improve dental treatment quality in patients with
      arterial hypertension. The study included 256 patients with arterial hypertension
      (153 females, 103 males) aged 35 to 60 years. Anesthesia efficacy was assessed by
      visual analog scale after treatment. Oral adverse effects caused by regular
      intake of antihypertensive drugs and interrelation with articaine and mepivacaine
      were described. The study proved high efficacy of 4% articaine 1:200 000. The
      efficacy of 3% mepivacaine with no vasoconstriction agents was 86.4+/-2.3% but
      may be enhanced to 93.3+/-2.3% by preventive non-steroid anti-inflammatory agents
      taken 25-30 minutes before treatment in maximal daily dosage.

PMID- 28514355
TI  - [The prevalence of tympanosclerosis and the effectiveness of its surgical
      treatment].
AB  - The objective of the present study was to characterize the epidemiological
      variants of tympanosclerosis and the effectiveness of the surgical treatment of
      the patients presenting with this condition. We have undertaken the analysis of
      the results of 1965 surgical interventions on the patients suffering from
      different forms of chronic otitis media (COM) performed during the period from
      2009 till 2014 with a view to determining the frequency of tympanosclerosis
      (TSC). In 542 cases, it proved possible to evaluate the intraoperative findings,
      stages and methods of reconstructive surgery, the anatomical and functional
      outcomes and effectiveness of the intervention. At present, the signs of
      tympanosclerosis are identified in 27.6% of the patients presenting with chronic
      otitis media including 88.7% and 11.3% suffering from the perforating and non
      perforating forms of this pathology, respectively. In 74% of the cases its
      manifestations are diagnosed in the patients having the tubotympanic form of COM.
      In 53.3% of the patients TSC foci are responsible for the fixation of the
      ossicular chain whereas in 46.7% of the cases the auditory ossicles retain
      mobility. As many as 88.6% of the patients underwent the one-step surgical
      intervention, 10.7% were managed using two-step surgery, and 0.7% of the patients
      were given the three-stage treatment. Type I tympanoplasty was performed in 62%
      of the patients, type III tympanoplasty in 30.4%, and various types of
      stapedoplasty in 4.6% of the cases. The favourable anatomical and functional
      outcomes at the first stage of the surgical intervention with the use of the
      autogenous tissues for tympano- and ossiculoplastic surgery were achieved in
      87.9% of the patients on the average (by means of the closure of the tympanic
      defect in 92.2% and by re-fixation of the selected elements of the ossicular
      chain in 17.3%of the cases). The anatomical and functional effectiveness of the
      second-stage surgical intervention was estimated at 93.1%.

PMID- 28514356
TI  - [The criteria for the relationship between hearing impairment and professional
      occupation and the criteria for professional suitability in terms of hearing
      among the aeronautical personnel engaged in civilian aviation].
AB  - This article describes the main clinical features associated with the development
      and manifestations of disturbed sound perception in the members of the
      aeronautical personnel engaged in the Russian civilian aviation. The main expert
      criteria for the relationship between the diseases of the organs of hearing (as
      exemplified by chronic sensorineural hearing impairment) and professional
      occupation have been developed based on the results of the clinical and
      diagnostic examination with the use of whispered and loud speech acumetry, tonal
      threshold audiometry, speech audiometry, impedancometry and evoked optoacoustic
      emission. Civilian aviation sectoral approaches to the evaluation of professional
      suitability in terms of hearing among the aeronautical personnel are considered
      in accordance with the criteria adopted by the International Civil Aviation
      Organization (ICAO), a specialized UN agency that sets the international
      standards for the civilian aviation and co-ordinates its development with the
      purpose of enhancing the safety and effectiveness of flights. The criteria are
      formulated for the solution of the expert problems arising from the relationship
      between the professional occupation and the diseases of the organs of hearing and
      for the evaluation of the professional suitability in terms of hearing among the
      aeronautical personnel engaged in civilian aviation.

PMID- 28514357
TI  - [The results of universal audiological screening of newborn infants in the
      Astrakhan region].
AB  - We have evaluated the results of universal audiological screening of 93 352
      newborn infants performed in the Astrakhan region of the Russian Federation
      during the period from 2009 till 2015. The screening coverage amounted to 95%.
      The prevalence of hearing disorders was estimated at 1:1111 and that of their
      severe forms at 1:3000. The clinical significance of the examination during its
      first stage consists of the exclusion of evoked otoacoustic emission. After the
      completion of the second stage, it is necessary to carry out the regular medical
      follow up observation of the children suffering from hearing impairment and to
      undertake the early rehabilitative treatment based on the application of hearing
      aids and prosthetic devices. Sensorineural hearing loss was found to be the
      predominant form of hearing disorders in the children during the first year of
      life (80%). The impairment of hearing was documented in 22.3% of the premature
      children which suggests the necessity of long-term monitoring of evoked
      otoacoustic emission in these patients.

PMID- 28514358
TI  - [Ionizing radiation and laryngeal cancer].
AB  - The cause behind the currently ever increasing number of patients presenting with
      laryngeal cancer lies not only in the lack of the apprehensive attitude toward
      oncological diseases among the medical profession but also in the changing
      conditions of human life and environment. As many as 165 patients suffering from
      laryngeal cancer of the 490 ones admitted to our clinic had undergone the
      influence of ionizing radiation before they were allocated to the main study
      group while the remaining 325 cases made up the control group. The former group
      included 112 firefighters of the Chernobyl disaster. It was shown that the
      progression rate of the disease among the patients of the main group was much
      higher than among those comprising the control one. A similar difference was
      documented in the occurrence of regional and remote metastases that were not
      infrequently the earliest manifestations of the disease. All the patients of the
      main study group were given the surgical treatment. The firefighters died within
      one year after the onset of the treatment due to multifocal tumours, regional and
      remote metastases.

PMID- 28514359
TI  - [The mathematical approaches to differential diagnostics of acute pharyngeal
      diseases].
AB  - The objective of the present study was to elaborate the program for differential
      diagnostics of acute pharyngeal diseases based on the 'ENT-Neuro' artificial
      neuronal network. The study group was formed by means of sampling patients with
      acute pharyngeal diseases from a set of case histories of the subjects presenting
      with acute inflammatory diseases. The data thus obtained were employed to develop
      the expert system to support the decision making process with the use of the 'ENT
      Neuro' artificial neuronal network that allows to carry out diagnostics of
      various inflammatory diseases of the pharynx including the following nosological
      entities: paratonsillitis, parapharyngitis, acute tonsillitis, and acute
      pharyngitis, with the minimal probability of erroneous diagnosis (4%). The
      proposed expert system makes it possible to choose the optimal treatment strategy
      for the management of various pharyngeal diseases taking into consideration the
      severity of a concrete pathology and thereby to reduce to a minimum the risk of
      the related complications.

PMID- 28514360
TI  - [Preoperative MRI diagnostics of the topographic features of neck arteries in the
      patients presenting with chronic tonsillitis].
AB  - The objective of the present study was to determine the frequency of
      abnormalities of the major neck vessels and elucidate the specific features of
      blood supply of palatine tonsil based on the results of MRI performed in the
      vasculature-targeting regimen. A total of 109 patients presenting with chronic
      tonsillitis (including 64 women and 45 men at the age varying from 15 to 54
      years) were available for the examination. All the patients underwent the MRI
      diagnostic study of the neck vessels by way of the preliminary evaluation of
      their condition at the pre-hospital stage. Abnormalities in the internal carotid
      artery were documented in 11.9% of the cases (including C- and S-shaped
      tortuosity of internal carotid artery in 6.88%, kinking and coiling of internal
      carotid artery in 4.13% and 0.92% of the patients, respectively). The majority of
      the detected abnormalities were located above the upper pole of the palatine
      tonsil which allowed to avoid the risk of the injury to the main neck vessels and
      prevented possible hemorrhage. One patient (0.46%) presented with kinking of the
      right internal carotid artery located in the immediate proximity to the capsule
      of the palatine tonsil close to its mid-third portion. There was no evidence that
      the present study gave rise to any malformation of the internal carotid artery
      and internal jugular vein. The proposed diagnostic method makes it possible to
      detect a rare anatomical feature of the development of the internal carotid
      artery discovered in a single patient (0.04%) out of the 2398 operated ones. This
      finding is of clinical significance and needs to be borne in mind when preparing
      the planned surgical intervention for the treatment of chronic tonsillitis. The
      results of the present study should be taken into consideration when prescribing
      the surgical treatment to the patients suffering not only from chronic
      tonsillitis but also from other ENT diseases, in the first place pharyngotympanic
      tube pathology.

PMID- 28514361
TI  - [The complications of transethmoidal decompressive orbitotomy associated with
      endocrine ophthalmopathy].
AB  - The objective of the present study was the analysis of the results of
      transethmoidal decompressive orbitotomy (TEDO) with the resection of the bone
      matrix of the medial and inferior orbital walls in the patients presenting with
      endocrine ophthalmopathy (EOP) with the purpose of reduction of the risk of
      development of this pathological conditions. A total of 51 patient with EOP at
      the stage of complete remission or pharmacotherapeutic compensation underwent
      transethmoidal decompressive medial orbitotomy in the ENT Clinic of 1 I.M.
      Sechenov First Moscow State Medical University during the period from 2006 to
      2016. Twenty two of these patients presented with the unilateral process and 29
      ones with bilateral exophthalmos. The surgical intervention was performed on the
      total of 80 eye orbits. The main complaints of the treated patients during the
      post-operative period included difficulties in nasal breathing (33%), dryness of
      the nose and crust formation (43%), discharge from the nose and along the
      posterior pharyngeal wall (15%), nasal bleeding (2%), pain in the forehead and
      maxillary region (8%), headache (2%). As far as the state of eyes and sight is
      concerned, 14 (27%) patients reported double vision at the primary gaze position
      while 6 others (12%) complained of the appearance of diplopia upon a change in
      the gaze position during the post-operative period. The post-operative endoscopic
      study revealed synechiae of different localization in the nasal cavity (47%),
      discharge from the maxillary sinuses (16%) and from the frontal sinus (2%). Eight
      (16%) patients were found to suffer from maxillary sinusitis, one had acute
      frontitis, and one sphenoidal sinus mucocelle. These complications were
      eliminated by pharmacotherapy and additional surgical interventions (2%).
      Analysis of the results of the study has demonstrated that the above
      complications were associated with the inadequate post-operative care for the
      nasal cavity, the excessively large size of the bone window formed during
      transethmoidal decompressive orbitotomy, resection of the inferior orbital wall,
      intrusion of the medial rectus muscle of the eye into the wide bone window. We
      evaluated the possible influence of the orbital soft tissues on the physiological
      parameters of the functioning of the paranasal sinuses in the post-operative
      period including blockade of the paranasal drainage pathways by the prolapsed
      orbital tissues. A few possible approaches to the reduction of the risk of post
      operative complications are proposed. The authors emphasize the importance of the
      further improvement of the surgical treatment of endocrine ophthalmopathy.

PMID- 28514362
TI  - [The laryngeal condition in the patients presenting with euthyroid multinodular
      goiter as evaluated by direct laryngoscopy].
AB  - The objective of the present study was to improve diagnostics of disturbances in
      the laryngeal condition of the patients presenting with euthyroid multinodular
      goiter with special reference to the condition of the upper respiratory passages.
      The preoperative characteristic of 398 patients included the description of the
      predominant clinical syndrome (the neoplastic and compressive variants) and
      specification of the morphological type of the disease to promote the decrease of
      operative activity with respect to colloidal proliferative goiter. Direct
      laryngoscopy was employed in addition to the traditional diagnostic techniques
      during both the surgical operation and the follow-up observation. Hoarseness
      developed in the postoperative period in 13.4% to 16.9% of the patients.
      Postoperative transient and persistent laryngeal paresis was documented in 1.5%
      and from 1.5% to 4.2% of the cases respectively. Direct laryngoscopy revealed the
      symptoms of laryngitis and laryngotracheitis as well as foci of leukoplakia,
      laryngeal cysts and nodules, besides disturbances in the mobility of the vocal
      chordae. It is concluded that the above pathological changes in the laryngeal
      structures should be identified during the preoperative examination of the
      patients presenting with euthyroid multinodular goiter while direct laryngoscopy
      must be included in the program of postoperative supervision.

PMID- 28514363
TI  - [The immunological characteristics and enzymatic activity of lymphocytes from the
      peripheral blood of the children presenting with pharyngeal tonsillar
      hypertrophy].
AB  - The objective of the present work was to study the immunological characteristics
      and activity of NAD(P)-dependent dehydrogenases in peripheral blood lymphocytes
      in the young children presenting with pharyngeal tonsil hypertrophy (PTH). A
      total of 57 children at the age from 1 to 3 years with PTH were available for the
      examination. The control group was comprised of 35 age-matched practically
      healthy children. The amount of CD3+, CD4+, CD8+, CD16+/56-, and CD19+ cells in
      the peripheral blood was determined with the use of the cytoflowmetric technique.
      The activity of NAD(P)-dependent dehydrogenases in the peripheral blood
      lymphocytes was quantified by the method of A.A. Savchenko and co-workers ([14].
      Serum IgA, IgM, and IgG levels were measured as described by G. Mancini and co
      workers [12], and the levels of the circulating immune complexes (CIC) by the
      method of Haskova and co-workers [13]. The children presenting with pharyngeal
      tonsil hypertrophy were found to undergo changes in the immune-phenotypic
      spectrum of peripheral bloods lymphocytes, the decrease of serum IgA
      concentration, and the increase in the serum CIC level. The activity of riboso-5
      phpsphate- and NADH-dependent reactions of the macromolecular synthesis was
      increased whereas the role of the malate-aspartate shunt in the cellular energy
      metabolism and activity of glycolysis decreased. On the contrary, the substrate
      flow in the tricarbonic acid cycle was rather high while glutathione reductase
      activity was low. The present study has shown that the children presenting with
      pharyngeal tonsil hypertrophy underwent changes in the immune and phenotypic
      spectrum of peripheral bloods lymphocytes, the decrease of serum IgA
      concentration, and the increase in the serum CIC level.

PMID- 28514364
TI  - [Radiodiagnostics of odontogenic maxillary sinusitis].
AB  - The objective of the present study was to analyze the potential of such
      techniques as X-ray, multi-slice computed tomography (MSCT), and cone-beam
      computed tomography (CBCT) for diagnostics of odontogenic maxillary sinusitis.
      The secondary objective was to describe changes in maxillary sinuses identifiable
      with the help of the above methods. The study included 166 patients at the age
      varying from 21 to 81 years presenting with odontogenic maxillary sinusitis. All
      of them underwent the roentgenological examination. The study has demonstrated
      the low effectiveness of the projection radiography techniques. The use of
      computed tomography made it possible to verify the diagnosis in 110 (66.2%) of
      the 166 examined patients, to reveal the radiological characteristics of the
      deyected changes suggesting their odontogenic etiology, and to choose the proper
      strategy for the further treatment. It is concluded that MSCT and CBCT are the
      most informative methods to be used for diagnostics of odontogenic maxillary
      sinusitis.

PMID- 28514365
TI  - [The detection of the human papilloma virus during hyperplastic processes in the
      nose, ears and throat].
AB  - The objective of the present work was to carry out the virological and
      histological studies of various neoplastic and hyperplastic processes in the
      nose, ears, and throat with a view to identifying the presence of human papilloma
      virus and Epstein-Barr virus. The brush biopsies and remote neoplasms obtained
      from 18 patients (including 2 children and 16 adults) presenting with various ENT
      diseases and tumours were available for the virological investigation with the
      use of the polymerase chain reaction (PCR) and a system MY09-MY11 degenerate
      primers . The histological study of biopsies and remote neoplasms was carried out
      by means of conventional light microscopy. The virological and histological
      studies conducted in parallel confirmed the diagnostic significance of
      morphological changes at the tissue and cellular levels caused by the human
      papilloma virus.

PMID- 28514366
TI  - [Applicability of antibacterial agents in chronic tonsillitis treatment].
AB  - The purpose of the present study was to evaluate the effectiveness of
      nitrofuranes applied for the treatment of chronic tonsillitis. A total of 92
      subjects divided into three cohorts were involved in this study. Cohort 1
      included 43 patients presenting with decompensated chronic tonsillitis and having
      pathogens in palatine tonsil lacunae. Cohort 2 was comprised of 13 patients with
      compensated chronic tonsillitis having pathogenic microflora of the same
      localization, while Cohort 3 was composed of 36 patients resembling those of
      cohort 1 in terms of clinical presentation, pathogen composition, and microbial
      spectrum. While the patients of cohort 1 and cohort 2 were treated by rinsing
      their tonsil lacunae with a furasol solution as a single-drug therapeutic
      procedure, those comprising Cohort 3 underwent treatment with furacilinum for the
      same purpose. The results of the study give evidence of the important advantages
      of furasol therapy over other modalities for the conservative treatment of
      chronic tonsillitis.

PMID- 28514367
TI  - [The new possibilities for the treatment of chronic cough associated with
      postnasal drip].
AB  - Cough is considered to be one of the leading clinical symptoms associated with
      the pathological changes in the respiratory system. Notwithstanding a great
      variety of therapeutic pharmaceutical products possessed of the antitussive
      action, physicians tend the give preference to the preparations producing the
      combined effect. The present article reports the results of the clinical study
      designed to evaluate the effectiveness and safety of the application of rengalin
      exhibiting the combined antitussive, anti-inflammatory, and broncholytic action
      in the patients presenting with the postnasal drip syndrome. The comparison of
      the therapeutic effects of rengalin with those of other therapeutic modalities
      frequently employed for the management of postnasal drip give evidence of the
      high efficiency of this product for the optimization of the treatment of this
      condition and the associated chronic cough.

PMID- 28514368
TI  - [The use of modern topical medications for the stepwise treatment of allergic
      rhinitis: the effectiveness and prospects for the further extension of their
      application].
AB  - The objective of the present work was to summarize the results of clinical
      studies designed to evaluate the effectiveness of 'Momate Rhino Advance' in the
      form of the nasal spray (based on the fixed combination of mometasone furoate and
      azelastine) that finds an increasingly wide application for the treatment of
      allergic rhinitis. The available data give evidence that this medication can be
      prescribed to the patients presenting with the severe and moderate form of
      allergic rhinitis. The treatment should be started with the use of the combined
      preparation and continued, after the adequate control of the clinical symptoms of
      allergic rhinitis is achieved, using 'Momate Rhino' during the next 2-4 weeks for
      the reliable management of the disease. It is concluded that the proposed
      strategy makes it possible to avoid the simultaneous application of multiple
      medications (polypragmasy) and thereby reduce the intake of medicines by the
      patients suffering from allergic rhinitis.

PMID- 28514369
TI  - [The role of topical glucocorticoids in the treatment of rhinosinusitis].
AB  - The guidelines of the European position paper on rhinosinusitis and nasal polyps
      (EPOS, 2012) ascribe the highest strength and the most comprehensive evidence
      based significance to the application of intranasal glucocorticosteroids (inGCS)
      as the first-line therapy for the patients presenting with acute and polypous
      rhinosinusitis; moreover they are recommended as the medications of choice for
      the treatment of chronic rhinosinusitis in the absence of polyps. The author
      presents the data concerning the mechanism of action, clinical effectiveness, and
      safety of inGCS used for the treatment of acute, recurrent, and chronic
      rhinosinusitis. It is shown that mometason furoate produces the favourable
      therapeutic effect and is possessed of beneficial pharmacodynamic and
      pharmacokinetic properties in the cases of its topical application. The
      comparative randomized clinical study (RCS) of the new preparation of mometason
      furoate in the form of the intranasal spray (manufactured by 'Teva' Ltd.)
      registered in the Russian Federation in 2015 has demonstrated that it can be
      considered as a therapeutic equivalent to nasonex.

PMID- 28514370
TI  - [Acute otitis media in a 5 year-old child complicated by mastoiditis and abscess
      of the temporomandibular joint].
AB  - This article was designed to report a case of otogenic abscess of the
      temporomandibular joint in a 5 year-old child. The specific feature of this
      observation is a rare complication of acute otitis media (otogenic abscess of the
      temporomandibular joint). Of crucial importance for the establishment of the
      correct diagnosis was the timely evaluation of the state of the temporomandibular
      bones by means of CT examination.

PMID- 28514371
TI  - [IgG4-related sclerosing disease of the larynx].
AB  - IgG4-related sclerosing disease of the larynx (IgG4-SD) is a recently described
      immunodependent systemic pathology characterized by diffusive or focal
      inflammatory infiltration of the affected organs and tissues by plasma cells
      expressing IgG4; it is accompanied by the subsequent development of obliterative
      phlebitis and fibrosclerosis associated with the increase of the serum IgG4
      level. According to the recently published materials, the disease can also
      develop in the respiratory system. The present article describes the first
      documented case of IgG4-related sclerosing disease with the isolated lesion of
      the larynx. The diagnosis was established based on the results of the
      comprehensive examination that made it possible to exclude systemic lesions, to
      determine the IgG4 level in the serum, and to carry out the immunohistochemical
      study of the histological preparations stained for the detection of IgG4
      releasing plasmocytes. After verification of the diagnosis, the patient underwent
      a course of systemic hormonal therapy that resulted in the stable clinical and
      roentgenological remission of the disease that persists up to the present time.

PMID- 28514372
TI  - [Secondary closed rhinoplasty in the patient presenting with post-injurious
      deformation of the external nose].
AB  - The authors describe the process of the surgical treatment of a patient
      presenting with the displaced fracture of the nasal bones involving the left
      orbital wall. The correction was performed by means of secondary closed
      rhinoseptoplastic surgery. The special emphasis is laid on the importance of
      computer-assisted modeling for the planning and achievement of the favourable
      surgical outcome.

PMID- 28514373
TI  - [Acute otitis media in the children: etiology and the problems of antibacterial
      therapy].
AB  - The objective of the present review was to summarize the currently available
      literature data on etiology of acute otitis media in the children, the role of
      biofilms in the development of this pathology, and sensitivity of its principal
      causative factors to various antibiotic medications. The secondary objective was
      to elaborate the practical guidelines for the prevention of acute otitis media in
      the children.

PMID- 28514374
TI  - [The role of the vomeronasal system in the formation of the human sexual
      behaviour].
AB  - This review deals with the structure and function of the vomeronasal system and
      evaluation of its influence on the sexual sphere of humans and animals. Special
      attention is given to the role of pheromones in the regulation of the sexual
      behaviour. The data concerning the function of the vomeronasal organ following
      surgical interventions in the nasal cavity are discussed.

PMID- 28514376
TI  - [Ray diagnostics and surgical tactics for chronic pancreatitis].

PMID- 28514375
TI  - [The etiopathogenetic aspects of idiopathic sensorineural impairment of hearing].
AB  - The objectives of the present work were the overview of the results of the modern
      investigations concerning etiology of idiopathic sensorineural impairment of
      hearing as well as the analysis of the theory of microthrombus formation and its
      role in pathogenesis of hearing impairment.

PMID- 28514377
TI  - [Iliac arteries and aortic repair in patients with retroperitoneal sarcoma].
AB  - AIM: To evaluate the results of surgical treatment in patients with
      retroperitoneal sarcoma and invasion into great vessels. MATERIAL AND METHODS:
      For the period 2009-2016 fourteenth patients with retroperitoneal sarcoma
      underwent resection and repair of great vessels at the abdominal department of
      N.N. Blokhin Russian Cancer Research Center. In 12 cases circular resection of
      infrarenal aorta, aortic bifurcation and iliac arteries followed by their
      replacement was made. 2 patients underwent circular resection of iliac arteries.
      RESULTS: Postoperative morbidity was 42.8%. There was no postoperative mortality.
      10 of 14 patients are alive from 2 to 70 months after surgery. One patient died
      in 2 months postoperatively from unknown reasons, 3 patients died in 18, 20 and
      30 months respectively due to progression of the disease. CONCLUSION: Overall
      survival and acceptable surgical risk underline the value of en block resection
      of retroperitoneal sarcoma together with involvement blood vessels.

PMID- 28514378
TI  - [Comparative analysis of static scintigraphy and computerized tomography in
      assessment of remnant liver volume after advanced hepatic resection].
AB  - AIM: To perform a comparative analysis of computerized tomographic volumetry and
      scintigraphic liver volumetry in assessment of remnant liver volume after
      advanced hepatic resection. MATERIAL AND METHODS: Static hepatobiliary
      scintigraphy and CT volumetry were performed in 45 patients with various liver
      tumors who underwent advanced hepatectomies (more than three segments). RESULTS:
      There were no any significant differences in volumetric parameters obtained by CT
      and scintigraphic volumetry. CONCLUSION: Scintigraphic volumetry data are similar
      to those of CT volumetry in evaluation of future remnant liver volume.
      Scintigraphic volumetry may be used as an alternative in assessment of future
      remnant liver volume after advanced hepatic resections.

PMID- 28514379
TI  - [Closed management of pancreatic necrosis complicated by diffuse peritonitis].
AB  - AIM: To assess an efficiency of closed management of pancreatic necrosis
      complicated by widespread peritonitis by using of elective laparoscopic sanations
      with ultrasonic processing of an abdominal cavity and retroperitoneal space.
      MATERIAL AND METHODS: Treatment of 111 patients with pancreatic necrosis
      complicated by diffuse peritonitis was analyzed. Closed management was used in 41
      patients (main group). Among them there were 12 patients who underwent
      laparoscopic sanation with ultrasonic cavitation of abdominal cavity,
      laparoscopic drainage of omental bag, US-assisted puncture drainage of
      retroperitoneal space and 29 patients after laparotomy followed by laparoscopic
      lavage and low-frequency ultrasound through retroperitoneal drains which were
      deployed during lumbotomy or under US control. Control group included 70 patients
      in whom open treatment of diffuse peritonitis was used (laparotomy, lumbotomy,
      omentobursostomy). Monitoring of hepatonephric dysfunction, endogenic
      intoxication was carried out. RESULTS: It was concluded that developed technique
      is associated with better clinical and laboratory data due to less surgical
      trauma and ultrasonic cavitation in early postoperative period. Rapid recovery of
      liver function, decrease of endogenic intoxication and mortality rate were
      observed. So, this method may be recommended for patients with pancreatic
      necrosis complicated by diffuse peritonitis.

PMID- 28514380
TI  - [Transcatheter embolization in prevention of recurrent bleeding from stomach
      ulcers].
AB  - AIM: To evaluate an efficacy of endovascular hemostasis in patients with gastric
      ulcerative bleeding and high risk of recurrent bleeding and death. MATERIAL AND
      METHODS: The work is based on a study of the results in 30 patients with gastric
      ulcerative bleeding, high risk of recurrent bleeding (rebleeding forecast system
      (RFS) score over 17) and high risk of death (SAPS II score over 30). We attempted
      transcatheter embolization of left gastric artery to prevent rebleeding. The
      control group consisted of 60 patients with gastric ulcerative bleeding and the
      same RFS and SAPS II values in whom angiography and endovascular hemostasis were
      not performed. RESULTS: Technical success of endovascular hemostasis was achieved
      in 25 (83.3%) cases. In 5 cases embolization was not performed. Complications
      after transcatheter angiography and embolization were absent. Recurrent bleeding
      after technically successful embolization was observed in 3 (12.0%) patients. In
      all cases PVA microemboli were used. Mortality was 11.1% (3 patients).
      CONCLUSION: Endovascular hemostasis in patients with severe comorbidities (SAPS
      II score over 30) and high risk of rebleeding (RFS score over 17) reduced
      incidence of recurrent bleeding from 36.7% to 11.1%.

PMID- 28514381
TI  - [Complications and long-term results of delayed esophagoezophagostomy for
      esophageal atresia].
AB  - AIM: To evaluate complications and long-term results of delayed
      esophagoesophagostomy in children with esophageal atresia (EA). MATERIAL AND
      METHODS: 165 EA children were operated at the Filatov Municipal Children's
      Hospital #13 for the period 2006-2016. Primary esophageal anastomosis was
      performed in 136 (82.4%) children with tracheoesophageal fistula. In 5 (3%)
      neonates with non-fistulous EA esophago- and gastrostomy were made for further
      coloesophagoplasty. Other 24 (14.5%) children underwent gastrostomy for delayed
      esophagoesophagostomy. 6 (25%) of them died within 12 days after admission. 18
      survivors with gastrostomy subsequently underwent delayed esophagoesophagostomy.
      RESULTS: Postoperative complications occurred in 16 (88.9%) children. Esophageal
      anastomosis failure occurred in 4 (22.2%) patients, stenosis of anastomosis in 11
      (61.1%) children, gastroesophageal reflux in 14 (77.8%) children. Early
      postoperative mortality was 16.7% (3 children). In remote period 92.3% of
      children were not adapted to normal diet and only in 7.7% of patients eating
      behavior corresponds to the age. 11 children underwent prolonged esophageal
      bougienage. 9 children underwent re-operation after delayed anastomosis.
      Esophageal extirpation was made in 4 children. CONCLUSION: Esophago- and
      gastrostomy provides 100% survival if primary esophageal anastomosis is
      impossible. Herewith, in children without esophagostomy mortality rate was 25%.
      We still can not confirm that delayed esophageal anastomosis is a good
      alternative for children with esophageal atresia. In view of our results the
      number of candidates for delayed esophageal anastomosis should be reduced.

PMID- 28514382
TI  - [Laser technologies in treatment of posttraumatic rectal fistulas].
AB  - AIM: To assess the results of surgical treatment of posttraumatic rectal fistulas
      using current laser technology. MATERIAL AND METHODS: Surgical treatment of 134
      (10.9%) patients with posttraumatic rectal fistulas was analyzed. The control
      group of conventional treatment included 58 (43.3+/-3.4%) patients, the main
      group - 76 (56.7+/-3.4%) patients. In the main group we used carbon dioxide laser
      device 'Lancet-2' (Russia) with a wavelength of 10.6 microns, capacity up to 20
      W, and contact laser device 'Atkus-15' (Russia) with a wavelength of 0.81 microns
      and output power up to 15W. In postoperative period all patients underwent daily
      infrared laser irradiation of wound surface with an exposure of 5-10 min,
      wavelength of 0.635+/-0.005 microns, output power 25 mW ('UZOR-3 KS' (Russia,
      Kaluga)). RESULTS: The complex surgical treatment with modern laser technologies
      have reduced the incidence of complications from 19.0+/-5.1% to 7.9+/-3.1%
      (OR=0.37; 95% CI; 0.13-1.06, p<0.05). The long-term results improved in 50.0+/
      13.4% of the control group and in 77.8+/-6.9% of the main group (chi2=5.22;
      p<0.05). CONCLUSION: Thus, laser technology has reduced twice the number of
      postoperative complications and improved long-ter. RESULTS: 98.2% of patients
      achieved medical and social rehabilitation in main group and 96.4% of patients in
      control group.

PMID- 28514383
TI  - [Efficiency of combined methods of hemorroid treatment using hal-rar and laser
      destruction].
AB  - AIM: To develop the combined method of treatment of hemorrhoids with arterial
      ligation under Doppler control and laser destruction of internal and external
      hemorrhoids. MATERIAL AND METHODS: The study included 100 patients with chronic
      hemorrhoids stage II and III. Combined method of HAL-laser was used in study
      group, HAL RAR-technique in control group 1 and closed hemorrhoidectomy with
      linear stapler in control group 2. Somparative evaluation of results in both
      groups was performed. RESULTS: Combined method overcomes the drawbacks of
      traditional surgical treatment and limitations in external components elimination
      which are inherent for HAL-RAR. Moreover, it has a higher efficiency in treating
      of hemorrhoids stage II-III compared with HAL-RAR and is equally safe and well
      tolerable for patients. This method does not increase the risk of recurrence,
      reduces incidence of complications and time of disability.

PMID- 28514385
TI  - [The effects of diosmin and hesperidin on capillary blood flow of upper limbs in
      patients with secondary Raynaud's syndrome].
AB  - The article discusses the effects of diosmin and hesperidin on capillary blood
      flow in patients with secondary Raynaud's syndrome (RS). Raynaud's syndrome a
      difficult problem of modern angiology, since in its development there is a large
      range of disorders of the capillary blood flow of the limbs. Currently, the main
      way of therapy in patients with secondary Raynaud's syndrome is the use of either
      calcium channel blockers (if angiospastic stage of the disease), or
      prostaglandins of group E1 (with tropho-paralytic stage of secondary RS).
      However, pharmacological effects of calcium channel blockers (vasodilation) and
      prostaglandins (vasodilation, antiproliferative, anti-inflammatory etc.) do not
      allow impact on all violations of capillary blood flow, occurs when the Raynaud's
      syndrome. In this regard, the task was to study the reaction of capillary blood
      flow of the fingers of the hands on the concomitant use of drugs based on diosmin
      and hesperidin. A prerequisite for the use of a combination of diosmin and
      hesperidin in the treatment of RS was based on data about their impact on the
      state of the venous segment of the capillary bed and perivascular oedema. To
      conduct the study was established two groups of patients (22 in each group). The
      main criterion for inclusion of patients in the study was the presence of newly
      identified Raynaud's syndrome of angiospastic or tropho-paralytic stage of the
      disease. The main exclusion criteria was the presence of necrotic stage of the
      disease. In the first group of patients therapy was carried out using only
      vasodilators. In the second group (comparison group) with the addition of a
      combination of diosmin and hesperidin (tablets Venarus used in a dose 500 mg 2
      times per day). The condition of capillary blood flow in this study was estimated
      by the method of videocapillaroscopy (VCS). Statistical data processing was
      performed using a criterion of statistical significance (P-value). The study
      revealed the significant impact of a combination of diosmin and hesperidin for
      parameters of capillary blood flow that correlated with clinical improvements -
      reduction of oedema of the fingers of the hands.

PMID- 28514384
TI  - [Innovative endoscopic technologies in multi-field medical facility].
AB  - The modern clinical practice is characterized by intensive introduction of
      innovative technologies for improving treatment and diagnostic procedures,
      minimizing their impact on the patient, complications rate and economic reasons.
      One of the priorities in this area is both diagnostic and therapeutic endoscopy.
      The degree of practical use of innovative endoscopic technologies depends on not
      only the quality of care, but also their economic reasons. Endoscopic treatment
      has become the method of choice for gastrointestional bleeding, extraction of
      foreign bodies, obstructive jaundice, polyps of the gastrointestinal tract,
      achalasia, esophageal strictures, etc. So, the current state of scientific and
      technical advances have made minimally invasive surgical intervention one of the
      main direction of development of surgery. The further improvement will be
      considered integration of minimally invasive and information technologies. The
      widespread introduction of minimally invasive surgical techniques in clinical
      practice indicates their undoubted efficiency and availability, especially in the
      multidisciplinary hospitals that provide various types of specialized high
      technological medical care. This allows to embody the principle of
      multidisciplinary and personalized approach in the treatment of patients. The
      main result of such practices is to reduce the duration of inpatient treatment, a
      significant reduction in the degree of invasive impact and risk of surgical
      interventions, diagnostic interventions and operations in a 'one-day hospital',
      with a total increase of efficiency of surgical treatment, and with high quality
      of life of patients.

PMID- 28514386
TI  - [Validity of test scales for neurocognitive and psychoemotional testing in
      patients with surgical pathology of precerebral arteries].

PMID- 28514387
TI  - [Postoperative abdominal hernia: a modern view on incidence and
      etiopathogenesis].

PMID- 28514388
TI  - [Conversion in laparoscopic surgery for colorectal cancer].

PMID- 28514389
TI  - [Acute bleeding from upper gastrointestinal tract due to splenic artery
      pseudoaneurysm in a cavity of pancreatic pseudocyst].

PMID- 28514390
TI  - [Gangliocytic paraganglioma of the duodenum].

PMID- 28514391
TI  - [Ectopic liver tissue in gallbladder's wall].

PMID- 28514392
TI  - [Direct oral anticoagulants in atrial fibrillation patients aged 75 years or
      older: Efficacy and safety balance].
AB  - Atrial fibrillation (AF) is one of the most common heart rhythm disorders in the
      population. Researchers revealed a direct relationship between their incidence
      and a patient's age long ago. One of the most challenging issues of clinical
      practice in patients with AF is anticoagulant therapy used in the so-called very
      elderly patients aged 75 years and older when age itself is a risk factor for
      developing both thromboembolic and hemorrhagic events due to anticoagulants,
      regardless of the mechanism of action of the latter. However, scientific data
      regarding the treatment and prevention of thromboembolic events in elderly and
      senile patients with AF are very scarce and often uninformative. The data from
      the EURObservational Research Programme-Atrial Fibrillation Registry Pilot Phase
      (EORP-AF Pilot) and the randomized clinical studies RELY, ROCKET AF, ARISTOTLE,
      and AVERROES were analyzed to identify the most safe and most effective
      anticoagulant for elderly patients (over 75 years). Relying on the analyses of
      literature data, the authors propose an algorithm based on clinical
      characteristics for choosing the anticoagulant for patients older than 75 years.

PMID- 28514393
TI  - [Subtraction CT angiopulmonographic assessment of the vascular bed and lung
      perfusion in patients with chronic thromboembolic pulmonary hypertension: A pilot
      study].
AB  - AIM: To evaluate the vascular bed and lung perfusion in patients with chronic
      thromboembolic pulmonary hypertension (CTEPH) by computed tomography (CT) and to
      compare the severity of pulmonary arterial (PA) thrombotic lesions concurrent
      with parenchymal perfusion disorders with angiopulmonographic findings and
      clinical and hemodynamic characteristics. SUBJECTS AND METHODS: In the period
      from November 2015 to May 2016, 22 patients (7 men, 15 women) aged 27 to 67 years
      with a verified diagnosis of CTEPH were examined using an Aquilion ONE VISION
      Edition 640 (Toshiba Medical Systems, Japan) CT scanner with a 320-row detector.
      Perfusion defect in this study was evaluated with the new software allowing one
      to combine contrast and contrast-free images by a subtraction method. CT data
      analysis included visual assessment of the vascular bed and lung parenchyma and
      quantitative assessment with perfusion map construction and semi-automatic
      determination of the obstruction index (OI) and perfusion defect index (PDI). OI
      was compared with PDI and mean LA pressure according to the data of right heart
      catheterization and 6-minute walk test. RESULTS: A statistically significant
      correlation was found between OI and PDI in patients with CTEPH (Pearson r=0.56;
      p=0.0065). There were no relationships between mean LA pressure and vascular
      perfusion indices (OI and PDI) or between vascular perfusion parameters and 6
      minute walk test results. CONCLUSION: CT angiopulmonography in conjunction with
      pulmonary perfusion assessment (within one study) allows evaluation of the
      severity of vascular lesions and perfusion disorders and determination of the
      efficiency of treatment in patients with CTEPH.

PMID- 28514394
TI  - [The diagnostic value of measuring the momentary blood flow reserve versus non
      invasive methods to detect myocardial ischemia in assessing the functional
      significance of borderline coronary artery stenoses].
AB  - AIM: To estimate the diagnostic value of measuring the momentary blood flow
      reserve (MBFR) versus the surrogate non-invasive standard (SNS) for myocardial
      ischemia verification (MIV) (a combination of stress echocardiography and single
      photon emission computed tomography). SUBJECTS AND METHODS: The investigation
      enrolled 50 patients with stable angina in the presence of chronic coronary heart
      disease (CHD) or suspected CHD, in whom coronary angiography (CA) revealed
      borderline coronary stenoses (50-70% lumen diameters). The examination algorithm
      had two options. In one option, when included in the study, patients had already
      CA results not older than 1 month, and MBFR was measured 4-7 days after non
      invasive stress tests. In the other option, MBFR in the area of borderline
      coronary artery stenosis was measured simultaneously with CA; and the noninvasive
      stress tests were carried out in the following week. A total of 74 coronary
      stenoses were examined. RESULTS: SNS for MIV was positive in 14 (28%) patients.
      When comparing with the non-invasive methods of myocardial ischemia verification,
      the area under the ROC curve for MBFR was 0.961+/-0.019 (95% confidence interval,
      0.888-0.992). The optimal cut-point was 0.92, which is corresponded by a
      sensitivity of 100% and a specificity of 84%. CONCLUSION: When compared with SNS
      for MIV, the method for measuring MBFR has a high diagnostic accuracy.

PMID- 28514395
TI  - [Impact of shock-wave therapy on the clinical and functional status of patients
      with coronary heart disease].
AB  - AIM: To study of the impact of shock-wave therapy (SWT) on the functional status
      of patients with coronary heart disease (CHD). SUBJECTS AND METHODS: Thirty-four
      CHD patients (including 33 men) with left ventricular (LV) asynergic segments, as
      evidenced by echocardiography (EchoCG), were examined. Their mean age was 60.1+/
      1.76 years. All the patients received a SWT cycle according to the standard
      scheme. The patient examination protocol involved EchoCG, dobutamine EchoCG,
      treadmill exercise EchoCG, and tissue Doppler EchoCG, which were performed at
      baseline, immediately and one month after the end of a SWT cycle. RESULTS:
      Following a SWT cycle, all the patients were noted to have a significant decrease
      in mean angina pectoris and heart failure functional classes and in the frequency
      of daily intake of nitrates. EchoCG showed that at baseline the LV ejection
      fraction (EF) was 51.1+/-1.02%; end- diastolic volume index, 71.5+/-3.6 ml/m2;
      end-systolic volume index, 34.4+/-2.2 ml/m2. According to exercise EchoCG, the
      tolerance threshold was 6.4+/-0.1 Mets (Bruce protocol); the total exercise time
      of 5.05+/-0.23 min was achieved in an average of 75.2+/-1.32%. Immediately and
      one month after a SWT cycle, there was an increment in EF from 51.1+/-1.02 to
      55+/-0.8 and 57+/-1.7%, respectively; a substantial increase in the tolerance
      threshold to 8.17+/-0.24 and 9.45+/-0.34 Mets, as compared to the baseline
      values. The exercise time increased up to 6.41+/-0.17 and 7.7+/-0.29 min
      immediately and one month after SWT, respectively. The increment in EF in
      response to exercise was 8.54+/-2.12, 14+/-1.5, and 16+/-1.2% at baseline,
      immediately and one month after SWT, respectively. Moreover, myocardial
      relaxation and diastolic function improved. CONCLUSION: Shock-wave therapy in
      patients with CHD is accompanied by their improved functional status, which is
      manifested by increased tolerance threshold and exercise duration, a rise in rest
      and exercise LV EF, better relaxation of LV, and its diminished stiffness.

PMID- 28514396
TI  - [Long-term results of different approaches to revascularization in non-ST-segment
      elevation acute coronary syndrome and multiple coronary atherosclerosis].
AB  - AIM: To assess the long-term results of different approaches to treating patients
      with non-ST-segment elevation acute coronary syndrome (NSTE ACS) and multivessel
      coronary artery disease (MVCAD). SUBJECTS AND METHODS: A total of 150 patients
      with NSTE ACS, in whom coronary angiography revealed MVCAD, were examined. The
      patients were divided into 3 groups according to the selected treatment policy:
      1) percutaneous coronary intervention (PCI) (n=91 (60.6%)); 2) coronary artery
      bypass grafting (CABG) (n=40 (26.6%)); and 3) only medical treatment (n=9 (6%)).
      The mean follow-up was 27.6+/-3.5 months. RESULTS: The medical treatment policy
      in this patient sample demonstrates the worst results, with the majority of
      cardiovascular events developing in the hospital period. PCI in patients with
      NSTE ACS and multiple coronary atherosclerosis has a number of objective
      limitations in this patient sample, leading to suboptimal treatment outcome.
      CONCLUSION: The use of CABG or PCI as a myocardial revascularization technique in
      patients with NSTE ACS and MVCAD is characterized by a comparable satisfactory
      survival in the hospital and long-term follow-up periods. 12% of patients do not
      receive revascularization due to the extremely high risk from any of coronary
      blood restoring methods, which results in very many deaths largely occurring
      during the hospital period.

PMID- 28514397
TI  - [Vascular permeability and intravascular erythrocyte aggregation in young people
      after smoking cessation].
AB  - AIM: To study the parameters of microcirculation and permeability of the
      microvessels in young people who have ceased smoking. SUBJECTS AND METHODS: The
      study enrolled 35 healthy young adults (male to female ratio, 20:15; mean age,
      21.71+/-0.46 years) who had stopped smoking 1 month to 10 years (mean 2.63+/-0.43
      years) ago. The compared group consisted of 16 smokers (male to female ratio,
      6:10; mean age, 21.62+/-0.72 years) and 29 non-smokers (male to female ratio,
      8:21; mean age, 21.62+/-0.48 years). Computer-assisted video biomicroscopy of the
      bulbar conjunctiva was performed. When the results were assessed, attention was
      drawn to a change in the degree and extent of intravascular erythrocyte
      aggregation (IVEA) and vessel wall permeability. RESULTS: As compared to the
      smokers, those who had quit smoking showed a decrease in the degree of IVEA in
      the arterioles (p1=0. 044, van der Waerden test), its prevalence in the central,
      transitional, and perilimbar regions (p1<0.0001), and a decline in the number of
      conjunctival areas that exhibited IVEA (2.2 and 3.437; p1=0.0002). Those who had
      given up smoking versus the smokers were found to have more rarely local foci of
      conjunctival edema (formation of veils; p1=0.0217). CONCLUSION: In the young
      people who have ceased smoking versus the smokers, IVEA decreases and
      miscovascular permeability restores.

PMID- 28514398
TI  - [Structural features of the lipid bilayer of the red blood cell membrane in
      people with isolated hypercholesterolemia without coronary artery disease and in
      patients with coronary artery disease].
AB  - AIM: To identify the specific features of modifying the lipid composition of the
      red blood cell membrane in people with isolated hypercholesterolemia without
      coronary heart disease (CHD) and in CHD patients with different functional
      classes of angina pectoris. SUBJECTS AND METHODS: 92 men with Functional Class II
      IV stable angina, 22 men with isolated hypercholesterolemia (HC) without CHD, and
      18 healthy men with normal cholesterol levels were examined. Blood plasma
      cholesterol levels were determined in all the examinees. The erythrocyte membrane
      was examined for the levels of lipid peroxidation (LPO) products, free
      cholesterol, calcium, and phospholipid fractions and for the activity of Na+/K+-,
      Mg2+- and Ca2+-ATPases; a bicycle exercise test was carried out. RESULTS: As
      compared with persons with normal blood cholesterol levels, the examinees with HC
      without CHD were found to have higher levels of LPO products, lower levels of
      readily oxidizable phospholipid fractions, decreased activity of membrane-bound
      Na+/K+-, Mg2+-, and Ca2+-ATPases, and elevated concentrations of free cholesterol
      and calcium in the red blood cell membrane. Having the pronounced activity of
      free radical oxidation, the patients with CHD were detected to have deeper
      similar structural changes in the cell membrane, which became more severe with a
      larger number of affected coronary arteries. CONCLUSION: The findings suggest
      that the lipid structure of the cell membrane undergoes changes associated with
      its functional depression just at the preclinical stage of atherogenesis.
      Biomembrane structural modification in patients with angina pectoris progresses
      in proportion to the number of affected coronary arteries, by limiting the
      functional reserve of the cell and whole body.

PMID- 28514399
TI  - [Disaccharidase deficiency and functional bowel diseases].
AB  - AIM: To elucidate the role of intestinal carbohydrases (glucoamylase, maltase,
      sucrose, and lactase) in the etiology and pathogenesis of functional bowel
      diseases (FBD). SUBJECTS AND METHODS: 74 patients (36 men and 38 women) aged 18
      to 50 years with FBD were examined. According to Rome IV criteria (2016), there
      was diarrhea-predominant irritable bowel syndrome (IBS) in 21 patients,
      functional diarrhea (FD) in 33, constipation-predominant IBS in 6, functional
      constipation (FC) in 4, and mixed IBS in 10. The activity of carbohydrases in the
      small intestine mucosa (SIM) was investigated by the Dahlquist method modified by
      Trinder in the duodenal biopsy specimens obtained during
      esophagogastroduodenoscopy. RESULTS: Lactase deficiency was identified in 87.8%
      of the patients; maltase deficiency in 48.6%; sucrose deficiency in 51.3%; and
      glucoamylase deficiency in 85.1%. The activity of all the investigated enzymes
      was reduced in 23 (31.1%) patients with FBD; deficiency of 1-3 carbohydrases was
      found in 47 (63.5%). Normal enzymatic activity was established in 4 (5.4%)
      patients. CONCLUSION: In the majority of patients with FBD, the intestinal
      symptoms are caused by the decreased activity of SIM carbohydrases. Therefore,
      disaccharidase deficiency associated with an established damaging agent
      (nonsteroidal anti-inflammatory drugs, antibiotics, acute intestinal infections,
      etc.) should be considered to be a more precise diagnosis.

PMID- 28514400
TI  - [Comparative characteristics of patients with gastroesophageal reflux disease in
      the age aspect].
AB  - AIM: To compare the characteristics of patients with gastroesophageal reflux
      disease (GERD) by age groups, a wide range of clinical signs, including life-of
      quality (QOL) indicators, and instrumental findings. SUBJECTS AND METHODS: A
      total of 110 patients aged 18 to 86 years with GERD were examined in accordance
      with the standard protocol. Two groups with equal numbers of patents were formed.
      A study group included elderly and senile patients and a control group consisted
      of young and adult ones. RESULTS: The elderly patients with GERD were observed to
      have a number of age-related clinical features and age-unrelated symptoms. The
      scores in the scales characterizing the physical health component and those in
      the general health and vital activity scales were markedly decreased in patients
      older than 60 years of age. No age-related statistically significant differences
      were found in the esophageal, gastric, and duodenal mucosae. Daily pH-metry in
      the elderly showed indirect evidence for esophageal hypomotor dyskinesia in the
      predominance of alkaline refluxes. CONCLUSION: The cohort of elderly patients
      with GERD was ascertained to have statistically significant clinical
      characteristics, and QOL and pH-metry indicators, which will be able to improve
      methods for diagnosis and early prevention in this age group.

PMID- 28514401
TI  - [Differentiation therapy for non-acidic gastroesophageal reflux disease].
AB  - AIM: To investigate the clinical and pathogenetic features of the non-acidic
      types of gastroesophageal reflux disease (GERD) and to evaluate the impact of
      combined therapy versus monotherapy on the course of this disease. SUBJECTS AND
      METHODS: The investigation enrolled 62 patients with non-acidic GERD. The follow
      up period was 6 weeks. The patients were divided into 2 groups: 1) weakly acidic
      gastroesophageal refluxes (GER); 2) weakly alkaline GER. Then each group was
      distributed, thus making up 4 groups: 1) 19 patients with weakly acidic GER who
      received monotherapy with rabeprazole 20 mg/day; 2) 21 patients with weakly
      acidic GER had combined therapy with rabeprazole 20 mg and itopride; 3) 8
      patients with weakly alkaline GER who received ursodeoxycholic acid (UDCA)
      monotherapy; and 4) 14 patients with weakly alkaline GER who had combined therapy
      with UDCA and itopride, The clinical symptoms of the disease, the endoscopic
      pattern of the upper gastrointestinal tract (GIT) mucosa, histological changes in
      the esophageal and gastric mucosa, and the results of 24-hour impedance pH
      monitoring were assessed over time. RESULTS: During differentiation therapy, the
      majority of patients reported positive clinical changes and an improved or
      unchanged endoscopic pattern. Assessment of impedance pH monitoring results
      revealed decreases in the overall number of GERs, the presence of a bolus in the
      esophagus, and the number of proximal refluxes. These changes were noted not only
      in patients taking proton pump inhibitors (PPIs), but also in those treated with
      UDCA monotherapy or combined PPI and prokinetic therapy. CONCLUSION: A
      differentiated approach to non-acidic GER treatment contributes to its
      efficiency. Adding the prokinetic itomed (itopride hydrochloride) to PPI therapy
      in a patient with weakly acidic GER enhances the efficiency of treatment, by
      positively affecting upper GIT motility. The mainstay of therapy for GERD with a
      predominance of weakly alkaline refluxes is UDCA, the combination of the latter
      and the prokinetic can exert a more pronounced effect on the clinical and
      endoscopic pattern and upper GIT motility.

PMID- 28514402
TI  - [Psychoemotional and autonomic states in patients with cholelithiasis].
AB  - AIM: To investigate the psychoemotional and autonomic states of patients with
      biliary system diseases and to determine their significance in the development of
      cholelithiasis. SUBJECTS AND METHODS: A total of 396 patients with stage 1
      cholelithiasis were examined. The results of hepatobiliary ultrasonography,
      multifractional duodenal probing, followed by macroscopic, microscopic, and
      biochemical examinations of bile (the total concentration of bile acids and
      cholesterol, by subsequently calculating the cholate-cholesterol ratio) were used
      to verify the diagnosis. The functional state of the hepatobiliary system was
      evaluated by dynamic echocholecystography and dynamic hepatobiliscintigraphy. To
      characterize the emotional state, the investigators applied indicators of the
      motivational sphere and orientation of an individual and his/her mental state,
      such as reactive anxiety, personal anxiety, the levels of depression and
      neuroticism, and intra-, extraversion. The autonomic state was determined from
      autonomic tone, autonomic reactivity, and autonomic support. RESULTS: Biliary
      lithogenesis was found to be related to psychoemotional and autonomic states. In
      cholelithiasis, there was an increase in reactive and personal anxiety and a
      predominance of diminished parasympathetic and perverted sympathetic autonomic
      reactivity. The signs of emotional instability and autonomic dystonia were shown
      to increase with age and the degree of an autonomic response depended on the
      severity of mental and emotional disorders. CONCLUSION: The results of these
      comprehensive studies can reveal new pathophysiological patterns of lithogenic
      bile formation and enhance our understanding of the pathogenesis of
      cholelithiasis.

PMID- 28514403
TI  - [Chronic constipation in the practice of a therapist: Features of therapy for
      comorbidity].
AB  - AIM: To evaluate the clinical efficacy of laxatives with different
      pharmacological effects in the combination therapy in patients with chronic
      constipation (CC) concurrent with obesity, hypertensive disease, and type 2
      diabetes mellitus (DM). SUBJECTS AND METHODS: A total of 110 people (45 men, 65
      women) aged 45 to 72 years with CC in the presence of concomitant diseases: grade
      1 or 2 hypertensive disease + obesity + type 2 DM. The investigators determined
      the severity of abdominal pain syndrome and flatulence, by indicating the mean
      frequency of defecations per week and fecal consistency according to the Bristol
      stool scale; anthropometric parameters; serum biochemistry tests; and serum
      lipoprotein phenotyping. Quality of life was assessed by the SF-36 questionnaire.
      The patients were divided into 3 groups according their use of agents: 1) dietary
      fiber (psyllium); 2) osmotic laxatives (disaccharides); 3) osmotic laxatives
      (polyethylene glycol). RESULTS: The patients taking psyllium to treat
      constipation showed an increasing frequency of defecations and normalization of
      stool consistency. Incorporating psyllium into combination therapy was
      accompanied by a significant decrease in the levels of total cholesterol and low
      density lipoprotein cholesterol. A similar trend was observed for serum
      triglycerides. The patients receiving combination therapy including other
      laxatives displayed no significant differences between lipid metabolic parameters
      at the beginning and after the end of treatment. CONCLUSION: The whole complex of
      properties of psyllium (Mucofalk) can be fully realized in patients with
      comorbidity and chronic constipation, which is accompanied not only by the
      normalization of bowel emptying, but also by marked positive changes in the main
      lipid metabolic parameters and by a reduction in overweight.

PMID- 28514404
TI  - [Emotional impairments and their correction in patients with migraine].
AB  - AIM: To study emotional impairments in patients with migraine and to evaluate the
      efficiency of Noophen therapy for this pathology. SUBJECTS AND METHODS: 63
      patients aged 18 to 45 years with migraine without aura were examined. 56
      patients used prophylactic antimigraine therapy: Group 1 (n = 26) received
      metoprolol and Group 2 took metoprolol in combination with Noophen. RESULTS: The
      patients with migraine had a significantly higher level of alexithymia than the
      controls. Concomitant anxiety disorders were found in 47 (74.6%) cases. The study
      provided evidence that the treatment was highly effective in Group 2 that
      exhibited a more pronounced decrease in pain intensity, a greater reduction in
      the levels of anxiety, and more vital activity. CONCLUSION: The results of this
      study allow a conclusion that emotional impairments are implicated in the
      pathogenesis and clinical presentations of migraine and that it is appropriate to
      use Noophen for the treatment of this pathology.

PMID- 28514405
TI  - [Stable high interleukin-17A concentration in patients with ankylosing
      spondylitis treated with tumor necrosis factor-alpha inhibitors during a year].
AB  - AIM: To assess changes in the concentration of interleukin-17A (IL-17A) in
      patients with ankylosing spondylitis (AS) treated with tumor necrosis factor
      alpha (TNFalpha) inhibitors during a year. SUBJECTS AND METHODS: Examinations
      were made in 30 patients (22 (73.3%) men) aged 38.35+/-9.19 years with AS
      (modified New-York criteria, BASDAI >=4.0; AS duration, 11.4+/-9.6 years) and in
      20 healthy individuals (12 (60%) men) aged 40.1+/-7.7 years) (a control group).
      All the patients were treated with infliximab (remicade, MSD) 5 mg/kg body weight
      during a year according to the recommended regimen. BASDAI and ASDAS were
      calculated; C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and
      TNFalpha and IL-17A concentrations were measured before and 52+/-2 weeks after
      TNFalpha inhibitors treatment. BASDAI/ASDAS improvement, ESR and CRP decreases;
      ASAS20/40 responses, ASAS partial remission, and an ASDAS improvement were
      estimated. RESULTS: In the patients with AS, the concentrations of TNFalpha and
      IL-17A were higher than those in the healthy individuals (p < 0.000). Twelve
      (40%) AS patients treated with TNFalpha inhibitors achieved ASAS partial
      remission. The average estimated back pain, ASDAS and BASDAI scores, and CRP and
      ESR substantially reduced (p<0.000 for all). The concentration of TNFalpha
      decreased from 17.8+/-7.6 to 7.3+/-3.2 pg/ml (p<0.000). The IL-17A level was
      28.4+/-14.4 and 32.1+/-12.2 pg/ml before and after the treatment, respectively.
      The baseline level of IL-17A was lower in the patients with AS who had achieved
      remission than that in those who had not (p=0.01). CONCLUSION: The improvement
      due to one-year AS treatment with TNFalpha inhibitors is not associated with the
      reduction of IL-17A concentrations. In the patients who failed to achieve ASAS
      partial remission, the baseline and final serum concentrations of IL-17A were
      higher than in those who achieved the remission.

PMID- 28514406
TI  - [A case of primary diagnosis of patent ductus arteriosus at the age of 75 years].
AB  - The paper describes a case of primary diagnosis of functioning patent ductus
      arteriosus in a 75-year-old female patient.

PMID- 28514407
TI  - [Osteoprotegerin is a new marker of cardiovascular diseases].
AB  - Osteoprotegerin (OPG) is a glycoprotein that is a representative of the tumor
      necrosis factor-alpha receptor superfamily. Information about the possible role
      of OPG in the development of cardiovascular diseases has begun to appear in the
      literature in recent years. This review discusses the role of increasing the
      level of OPG in the development and progression of atherosclerosis and as a
      consequence of coronary heart disease and chronic heart failure.

PMID- 28514408
TI  - [Asymptomatic atherosclerosis of the brachiocephalic arteries: Current approaches
      to diagnosis and treatment].
AB  - Acute cerebrovascular accident (ACVA) and transient ischemic attack are among the
      leading causes of morbidity, disability, and mortality in the Russian Federation
      and the world. Ischemic strokes account for 70-80% of all ACVAs, with 20-30% of
      them being associated with stenotic atherosclerosis of the brachiocephalic
      arteries (BCA). The paper describes modern views on the problem of asymptomatic
      BCA atherosclerosis and considers the possibilities of identifying risk groups
      among the patients with asymptomatic atherosclerosis of the BCA.

PMID- 28514410
TI  - [Cryoglobulinemic vasculitis in chronic hepatitis C: Genetic aspects].
AB  - Cryoglobulinemia (CG) is detected in more than 50% of patients with chronic
      hepatitis C (CHC); however, only 15-25% of them develop cryoglobulinemic
      vasculitis (CV) that is a systemic vasculitis due to the formation of immune
      deposits, which affects small (less than medium-sized) vessels and which is
      frequently fatal for the patient. The causes of CG only in some patients with CHC
      and the pathogenesis of CV remain unstudied; however, the accumulated data allow
      one to identify the special contribution of the patient's genetic factors to the
      development of the disease. The paper considers the genetic aspects of the
      development of CG and CV in CHC.

PMID- 28514409
TI  - [New opportunities for the prevention of gastric cancer].
AB  - The approvals and provisions of the Management of Helicobacter pylori infection
      the Maastricht V/ Florence Consensus Report and those of the Kyoto Global
      Consensus Conference on H. pylori-associated gastritis, concerning with the
      primary and secondary prevention of gastric cancer (GC), unambiguously suggest
      that H. pylori infection is the most important risk factor of GC. Accordingly,
      the basis for the primary and secondary prevention of GC is the optimization of
      H. pylori eradication therapy. The clear direct relationship of the risk of GC to
      the severity and extent of atrophic gastritis, intestinal metaplasia and
      dysplasia and no reversal of intestinal metaplasia and dysplasia in the presence
      of H. pylori eradication presume that gastroprotective agents should be used for
      primary and secondary prevention. Experimental and clinical findings can lead to
      the conclusion that rebamipide is a highly effective and safe agent for the
      primary and secondary prevention of GC in patients with and without H. pylori
      infection, by optimizing anti-Helicobacter therapy, its anti-inflammatory effect
      and ability to restore the cellular structure of the gastric epithelium.

PMID- 28514411
TI  - [Langerhans cell histiocytosis: Skin diseases and visceral lesions].
AB  - Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder that
      belongs to class I histiocytoses and is characterized by infiltration of one or
      many organs by Langerhans cells to form granulomas. The literature analysis could
      identify a lot of etiological, pathogenetic, and trigger factors and mechanisms
      for LCH development, which determine the diversity of the clinical picture and
      course of the disease. The clinical manifestations of LCH are very variable and
      depend on the severity of lesions and the age of patients. In addition to skin
      lesions, there is involvement of one or more visceral organs. Difficulties in
      diagnosing the disease lead to statistical variations of LCH in different
      countries of the world and require more attention by physicians of all
      specialties.

PMID- 28514413
TI  - University spin-offs.

PMID- 28514412
TI  - Therapeutic developments: Masters of medicine.

PMID- 28514414
TI  - Clinical devices and services: Repair shops.

PMID- 28514416
TI  - Energy: Powering change.

PMID- 28514415
TI  - Materials and engineering: Rebuilding the world.

PMID- 28514417
TI  - Software: Picture perfect.

PMID- 28514419
TI  - Erratum: Full antagonism of the estrogen receptor without a prototypical ligand
      side chain.

PMID- 28514421
TI  - Small-molecule phenotypic screening with stem cells.

PMID- 28514422
TI  - Shaping embryonic development.

PMID- 28514424
TI  - Corrigendum: Full antagonism of the estrogen receptor without a prototypical
      ligand side chain.

PMID- 28514418
TI  - Small-molecule pheromones and hormones controlling nematode development.
AB  - The existence of small-molecule signals that influence development in
      Caenorhabditis elegans has been known for several decades, but only in recent
      years have the chemical structures of several of these signals been established.
      The identification of these signals has enabled connections to be made between
      these small molecules and fundamental signaling pathways in C. elegans that
      influence not only development but also metabolism, fertility, and lifespan.
      Spurred by these important discoveries and aided by recent advances in
      comparative metabolomics and NMR spectroscopy, the field of nematode chemistry
      has the potential to expand dramatically in the coming years. This Perspective
      will focus on small-molecule pheromones and hormones that influence developmental
      events in the nematode life cycle (ascarosides, dafachronic acids, and
      nemamides), will cover more recent work regarding the biosynthesis of these
      signals, and will explore how the discovery of these signals is transforming our
      understanding of nematode development and physiology.

PMID- 28514425
TI  - Signal Transduction: Notch catches a Jagged edge.

PMID- 28514428
TI  - Unraveling cell-to-cell signaling networks with chemical biology.

PMID- 28514429
TI  - Optogenetics: Switching with red and blue.

PMID- 28514427
TI  - Illuminating developmental biology through photochemistry.
AB  - Developmental biology has been continually shaped by technological advances,
      evolving from a descriptive science into one immersed in molecular and cellular
      mechanisms. Most recently, genome sequencing and 'omics' profiling have provided
      developmental biologists with a wealth of genetic and biochemical information;
      however, fully translating this knowledge into functional understanding will
      require new experimental capabilities. Photoactivatable probes have emerged as
      particularly valuable tools for investigating developmental mechanisms, as they
      can enable rapid, specific manipulations of DNA, RNA, proteins, and cells with
      spatiotemporal precision. In this Perspective, we describe optochemical and
      optogenetic systems that have been applied in multicellular organisms, insights
      gained through the use of these probes, and their current limitations. We also
      suggest how chemical biologists can expand the reach of photoactivatable
      technologies and bring new depth to our understanding of organismal development.

PMID- 28514430
TI  - Erratum: A Vibrio cholerae autoinducer-receptor pair that controls biofilm
      formation.

PMID- 28514433
TI  - The genetic microscope.

PMID- 28514434
TI  - Q&A: Jim McCluskey.

PMID- 28514435
TI  - Career guide Melbourne.

PMID- 28514436
TI  - Q&A: Victoria Blair.

PMID- 28514432
TI  - The perception of strigolactones in vascular plants.
AB  - Small-molecule hormones play central roles in plant development, ranging from
      cellular differentiation and organ formation to developmental response
      instruction in changing environments. A recently discovered collection of related
      small molecules collectively called strigolactones are of particular interest, as
      these hormones also function as ecological communicators between plants and fungi
      and between parasitic plants and their hosts. Advances from model plant systems
      have begun to unravel how, as a hormone, strigolactone is perceived and
      transduced. In this Review, we summarize this information and examine how
      understanding strigolactone hormone signaling is leading to insights into
      parasitic plant infections. We specifically focus on how the development of
      chemical probes can be used in combination with model plant systems to dissect
      strigolactone's perception in the parasitic plant Striga hermonthica. This
      information is particularly relevant since Striga is considered one of the
      largest impediments to food security in sub-Saharan Africa.

PMID- 28514437
TI  - China's Silicon Valley.

PMID- 28514438
TI  - Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
AB  - Developmental pathways that orchestrate the fleeting transition of endothelial
      cells into haematopoietic stem cells remain undefined. Here we demonstrate a
      tractable approach for fully reprogramming adult mouse endothelial cells to
      haematopoietic stem cells (rEC-HSCs) through transient expression of the
      transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively
      denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The
      induction phase (days 0-8) of conversion is initiated by expression of FGRS in
      mature endothelial cells, which results in endogenous Runx1 expression. During
      the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells
      commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS
      expression. The vascular niche drives a robust self-renewal and expansion phase
      of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self
      renewal capacity similar to those of adult haematopoietic stem cells, and can be
      used for clonal engraftment and serial primary and secondary multi-lineage
      reconstitution, including antigen-dependent adaptive immune function. Inhibition
      of TGFbeta and CXCR7 or activation of BMP and CXCR4 signalling enhanced
      generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells
      into autologous authentic engraftable haematopoietic stem cells could aid
      treatment of haematological disorders.

PMID- 28514439
TI  - Haematopoietic stem and progenitor cells from human pluripotent stem cells.
AB  - A variety of tissue lineages can be differentiated from pluripotent stem cells by
      mimicking embryonic development through stepwise exposure to morphogens, or by
      conversion of one differentiated cell type into another by enforced expression of
      master transcription factors. Here, to yield functional human haematopoietic stem
      cells, we perform morphogen-directed differentiation of human pluripotent stem
      cells into haemogenic endothelium followed by screening of 26 candidate
      haematopoietic stem-cell-specifying transcription factors for their capacity to
      promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven
      transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are
      sufficient to convert haemogenic endothelium into haematopoietic stem and
      progenitor cells that engraft myeloid, B and T cells in primary and secondary
      mouse recipients. Our combined approach of morphogen-driven differentiation and
      transcription-factor-mediated cell fate conversion produces haematopoietic stem
      and progenitor cells from pluripotent stem cells and holds promise for modelling
      haematopoietic disease in humanized mice and for therapeutic strategies in
      genetic blood disorders.

PMID- 28514440
TI  - Extreme hydrothermal conditions at an active plate-bounding fault.
AB  - Temperature and fluid pressure conditions control rock deformation and
      mineralization on geological faults, and hence the distribution of earthquakes.
      Typical intraplate continental crust has hydrostatic fluid pressure and a near
      surface thermal gradient of 31 +/- 15 degrees Celsius per kilometre. At
      temperatures above 300-450 degrees Celsius, usually found at depths greater than
      10-15 kilometres, the intra-crystalline plasticity of quartz and feldspar
      relieves stress by aseismic creep and earthquakes are infrequent. Hydrothermal
      conditions control the stability of mineral phases and hence frictional
      mechanical processes associated with earthquake rupture cycles, but there are few
      temperature and fluid pressure data from active plate-bounding faults. Here we
      report results from a borehole drilled into the upper part of the Alpine Fault,
      which is late in its cycle of stress accumulation and expected to rupture in a
      magnitude 8 earthquake in the coming decades. The borehole (depth 893 metres)
      revealed a pore fluid pressure gradient exceeding 9 +/- 1 per cent above
      hydrostatic levels and an average geothermal gradient of 125 +/- 55 degrees
      Celsius per kilometre within the hanging wall of the fault. These extreme
      hydrothermal conditions result from rapid fault movement, which transports rock
      and heat from depth, and topographically driven fluid movement that concentrates
      heat into valleys. Shear heating may occur within the fault but is not required
      to explain our observations. Our data and models show that highly anomalous fluid
      pressure and temperature gradients in the upper part of the seismogenic zone can
      be created by positive feedbacks between processes of fault slip, rock fracturing
      and alteration, and landscape development at plate-bounding faults.

PMID- 28514441
TI  - PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour
      immunity.
AB  - Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is
      upregulated on activated T cells for the induction of immune tolerance. Tumour
      cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1
      (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies
      that block the interaction between PD-1 and PD-L1, by binding to either the
      ligand or receptor, have shown notable clinical efficacy in patients with a
      variety of cancers, including melanoma, colorectal cancer, non-small-cell lung
      cancer and Hodgkin's lymphoma. Although it is well established that PD-1-PD-L1
      blockade activates T cells, little is known about the role that this pathway may
      have in tumour-associated macrophages (TAMs). Here we show that both mouse and
      human TAMs express PD-1. TAM PD-1 expression increases over time in mouse models
      of cancer and with increasing disease stage in primary human cancers. TAM PD-1
      expression correlates negatively with phagocytic potency against tumour cells,
      and blockade of PD-1-PD-L1 in vivo increases macrophage phagocytosis, reduces
      tumour growth and lengthens the survival of mice in mouse models of cancer in a
      macrophage-dependent fashion. This suggests that PD-1-PD-L1 therapies may also
      function through a direct effect on macrophages, with substantial implications
      for the treatment of cancer with these agents.

PMID- 28514444
TI  - Plant biology: An immunity boost combats crop disease.

PMID- 28514442
TI  - Architecture of the human interactome defines protein communities and disease
      networks.
AB  - The physiology of a cell can be viewed as the product of thousands of proteins
      acting in concert to shape the cellular response. Coordination is achieved in
      part through networks of protein-protein interactions that assemble functionally
      related proteins into complexes, organelles, and signal transduction pathways.
      Understanding the architecture of the human proteome has the potential to inform
      cellular, structural, and evolutionary mechanisms and is critical to elucidating
      how genome variation contributes to disease. Here we present BioPlex 2.0
      (Biophysical Interactions of ORFeome-derived complexes), which uses robust
      affinity purification-mass spectrometry methodology to elucidate protein
      interaction networks and co-complexes nucleated by more than 25% of protein
      coding genes from the human genome, and constitutes, to our knowledge, the
      largest such network so far. With more than 56,000 candidate interactions,
      BioPlex 2.0 contains more than 29,000 previously unknown co-associations and
      provides functional insights into hundreds of poorly characterized proteins while
      enhancing network-based analyses of domain associations, subcellular
      localization, and co-complex formation. Unsupervised Markov clustering of
      interacting proteins identified more than 1,300 protein communities representing
      diverse cellular activities. Genes essential for cell fitness are enriched within
      53 communities representing central cellular functions. Moreover, we identified
      442 communities associated with more than 2,000 disease annotations, placing
      numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds
      previous experimentally derived interaction networks in depth and breadth, and
      will be a valuable resource for exploring the biology of incompletely
      characterized proteins and for elucidating larger-scale patterns of proteome
      organization.

PMID- 28514443
TI  - Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.
AB  - Reprogrammed cellular metabolism is a common characteristic observed in various
      cancers. However, whether metabolic changes directly regulate cancer development
      and progression remains poorly understood. Here we show that BCAT1, a cytosolic
      aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated
      and functionally required for chronic myeloid leukaemia (CML) in humans and in
      mouse models of CML. BCAT1 is upregulated during progression of CML and promotes
      BCAA production in leukaemia cells by aminating the branched-chain keto acids.
      Blocking BCAT1 gene expression or enzymatic activity induces cellular
      differentiation and impairs the propagation of blast crisis CML both in vitro and
      in vivo. Stable-isotope tracer experiments combined with nuclear magnetic
      resonance-based metabolic analysis demonstrate the intracellular production of
      BCAAs by BCAT1. Direct supplementation with BCAAs ameliorates the defects caused
      by BCAT1 knockdown, indicating that BCAT1 exerts its oncogenic function through
      BCAA production in blast crisis CML cells. Importantly, BCAT1 expression not only
      is activated in human blast crisis CML and de novo acute myeloid leukaemia, but
      also predicts disease outcome in patients. As an upstream regulator of BCAT1
      expression, we identified Musashi2 (MSI2), an oncogenic RNA binding protein that
      is required for blast crisis CML. MSI2 is physically associated with the BCAT1
      transcript and positively regulates its protein expression in leukaemia. Taken
      together, this work reveals that altered BCAA metabolism activated through the
      MSI2-BCAT1 axis drives cancer progression in myeloid leukaemia.

PMID- 28514445
TI  - Blood: Education for stem cells.

PMID- 28514447
TI  - Global translational reprogramming is a fundamental layer of immune regulation in
      plants.
AB  - In the absence of specialized immune cells, the need for plants to reprogram
      transcription to transition from growth-related activities to defence is well
      understood. However, little is known about translational changes that occur
      during immune induction. Using ribosome footprinting, here we perform global
      translatome profiling on Arabidopsis exposed to the microbe-associated molecular
      pattern elf18. We find that during this pattern-triggered immunity, translation
      is tightly regulated and poorly correlated with transcription. Identification of
      genes with altered translational efficiency leads to the discovery of novel
      regulators of this immune response. Further investigation of these genes shows
      that messenger RNA sequence features are major determinants of the observed
      translational efficiency changes. In the 5' leader sequences of transcripts with
      increased translational efficiency, we find a highly enriched messenger RNA
      consensus sequence, R-motif, consisting of mostly purines. We show that R-motif
      regulates translation in response to pattern-triggered immunity induction through
      interaction with poly(A)-binding proteins. Therefore, this study provides not
      only strong evidence, but also a molecular mechanism, for global translational
      reprogramming during pattern-triggered immunity in plants.

PMID- 28514446
TI  - Identification of preoptic sleep neurons using retrograde labelling and gene
      profiling.
AB  - In humans and other mammalian species, lesions in the preoptic area of the
      hypothalamus cause profound sleep impairment, indicating a crucial role of the
      preoptic area in sleep generation. However, the underlying circuit mechanism
      remains poorly understood. Electrophysiological recordings and c-Fos
      immunohistochemistry have shown the existence of sleep-active neurons in the
      preoptic area, especially in the ventrolateral preoptic area and median preoptic
      nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has
      been shown to induce sleep. However, the sleep-active neurons are spatially
      intermingled with wake-active neurons, making it difficult to target the sleep
      neurons specifically for circuit analysis. Here we identify a population of
      preoptic area sleep neurons on the basis of their projection target and discover
      their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a
      light-activated chloride channel for retrograde labelling, bidirectional
      optogenetic manipulation, and optrode recording, we show that the preoptic area
      GABAergic neurons projecting to the tuberomammillary nucleus are both sleep
      active and sleep promoting. Furthermore, translating ribosome affinity
      purification and single-cell RNA sequencing identify candidate markers for these
      neurons, and optogenetic and pharmacogenetic manipulations demonstrate that
      several peptide markers (cholecystokinin, corticotropin-releasing hormone, and
      tachykinin 1) label sleep-promoting neurons. Together, these findings provide
      easy genetic access to sleep-promoting preoptic area neurons and a valuable entry
      point for dissecting the sleep control circuit.

PMID- 28514448
TI  - uORF-mediated translation allows engineered plant disease resistance without
      fitness costs.
AB  - Controlling plant disease has been a struggle for humankind since the advent of
      agriculture. Studies of plant immune mechanisms have led to strategies of
      engineering resistant crops through ectopic transcription of plants' own defence
      genes, such as the master immune regulatory gene NPR1 (ref. 1). However, enhanced
      resistance obtained through such strategies is often associated with substantial
      penalties to fitness, making the resulting products undesirable for agricultural
      applications. To remedy this problem, we sought more stringent mechanisms of
      expressing defence proteins. On the basis of our latest finding that translation
      of key immune regulators, such as TBF1 (ref. 3), is rapidly and transiently
      induced upon pathogen challenge (see accompanying paper), we developed a 'TBF1
      cassette' consisting of not only the immune-inducible promoter but also two
      pathogen-responsive upstream open reading frames (uORFsTBF1) of the TBF1 gene.
      Here we demonstrate that inclusion of uORFsTBF1-mediated translational control
      over the production of snc1-1 (an autoactivated immune receptor) in Arabidopsis
      thaliana and AtNPR1 in rice enables us to engineer broad-spectrum disease
      resistance without compromising plant fitness in the laboratory or in the field.
      This broadly applicable strategy may lead to decreased pesticide use and reduce
      the selective pressure for resistant pathogens.

PMID- 28514449
TI  - Human GLP-1 receptor transmembrane domain structure in complex with allosteric
      modulators.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR)
      are members of the secretin-like class B family of G-protein-coupled receptors
      (GPCRs) and have opposing physiological roles in insulin release and glucose
      homeostasis. The treatment of type 2 diabetes requires positive modulation of GLP
      1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose
      dependent manner. Here we report crystal structures of the human GLP-1R
      transmembrane domain in complex with two different negative allosteric
      modulators, PF-06372222 and NNC0640, at 2.7 and 3.0 A resolution, respectively.
      The structures reveal a common binding pocket for negative allosteric modulators,
      present in both GLP-1R and GCGR and located outside helices V-VII near the
      intracellular half of the receptor. The receptor is in an inactive conformation
      with compounds that restrict movement of the intracellular tip of helix VI, a
      movement that is generally associated with activation mechanisms in class A
      GPCRs. Molecular modelling and mutagenesis studies indicate that agonist positive
      allosteric modulators target the same general region, but in a distinct sub
      pocket at the interface between helices V and VI, which may facilitate the
      formation of an intracellular binding site that enhances G-protein coupling.

PMID- 28514450
TI  - Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes.
AB  - Zika virus (ZIKV) remained obscure until the recent explosive outbreaks in French
      Polynesia (2013-2014) and South America (2015-2016). Phylogenetic studies have
      shown that ZIKV has evolved into African and Asian lineages. The Asian lineage of
      ZIKV was responsible for the recent epidemics in the Americas. However, the
      underlying mechanisms through which ZIKV rapidly and explosively spread from Asia
      to the Americas are unclear. Non-structural protein 1 (NS1) facilitates
      flavivirus acquisition by mosquitoes from an infected mammalian host and
      subsequently enhances viral prevalence in mosquitoes. Here we show that NS1
      antigenaemia determines ZIKV infectivity in its mosquito vector Aedes aegypti,
      which acquires ZIKV via a blood meal. Clinical isolates from the most recent
      outbreak in the Americas were much more infectious in mosquitoes than the
      FSS13025 strain, which was isolated in Cambodia in 2010. Further analyses showed
      that these epidemic strains have higher NS1 antigenaemia than the FSS13025 strain
      because of an alanine-to-valine amino acid substitution at residue 188 in NS1.
      ZIKV infectivity was enhanced by this amino acid substitution in the ZIKV
      FSS13025 strain in mosquitoes that acquired ZIKV from a viraemic C57BL/6 mouse
      deficient in type I and II interferon (IFN) receptors (AG6 mouse). Our results
      reveal that ZIKV evolved to acquire a spontaneous mutation in its NS1 protein,
      resulting in increased NS1 antigenaemia. Enhancement of NS1 antigenaemia in
      infected hosts promotes ZIKV infectivity and prevalence in mosquitoes, which
      could have facilitated transmission during recent ZIKV epidemics.

PMID- 28514452
TI  - Isotopic evidence of multiple controls on atmospheric oxidants over climate
      transitions.
AB  - The abundance of tropospheric oxidants, such as ozone (O3) and hydroxyl (OH) and
      peroxy radicals (HO2 + RO2), determines the lifetimes of reduced trace gases such
      as methane and the production of particulate matter important for climate and
      human health. The response of tropospheric oxidants to climate change is poorly
      constrained owing to large uncertainties in the degree to which processes that
      influence oxidants may change with climate and owing to a lack of palaeo-records
      with which to constrain levels of atmospheric oxidants during past climate
      transitions. At present, it is thought that temperature-dependent emissions of
      tropospheric O3 precursors and water vapour abundance determine the climate
      response of oxidants, resulting in lower tropospheric O3 in cold climates while
      HOx (= OH + HO2 + RO2) remains relatively buffered. Here we report observations
      of oxygen-17 excess of nitrate (a proxy for the relative abundance of atmospheric
      O3 and HOx) from a Greenland ice core over the most recent glacial-interglacial
      cycle and for two Dansgaard-Oeschger events. We find that tropospheric oxidants
      are sensitive to climate change with an increase in the O3/HOx ratio in cold
      climates, the opposite of current expectations. We hypothesize that the observed
      increase in O3/HOx in cold climates is driven by enhanced stratosphere-to
      troposphere transport of O3, and that reactive halogen chemistry is also enhanced
      in cold climates. Reactive halogens influence the oxidative capacity of the
      troposphere directly as oxidants themselves and indirectly via their influence on
      O3 and HOx. The strength of stratosphere-to-troposphere transport is largely
      controlled by the Brewer-Dobson circulation, which may be enhanced in colder
      climates owing to a stronger meridional gradient of sea surface temperatures,
      with implications for the response of tropospheric oxidants and stratospheric
      thermal and mass balance. These two processes may represent important, yet
      relatively unexplored, climate feedback mechanisms during major climate
      transitions.

PMID- 28514455
TI  - Precision Psychiatry Meets Network Medicine: Network Psychiatry.

PMID- 28514456
TI  - Correction of 95% CI in Table.

PMID- 28514457
TI  - Omission in Funding/Support Section.

PMID- 28514453
TI  - Chromatin states define tumour-specific T cell dysfunction and reprogramming.
AB  - Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours
      to progress. The epigenetic regulation of T cell dysfunction and therapeutic
      reprogrammability (for example, to immune checkpoint blockade) is not well
      understood. Here we show that T cells in mouse tumours differentiate through two
      discrete chromatin states: a plastic dysfunctional state from which T cells can
      be rescued, and a fixed dysfunctional state in which the cells are resistant to
      reprogramming. We identified surface markers associated with each chromatin state
      that distinguished reprogrammable from non-reprogrammable PD1hi dysfunctional T
      cells within heterogeneous T cell populations from tumours in mice; these surface
      markers were also expressed on human PD1hi tumour-infiltrating CD8 T cells. Our
      study has important implications for cancer immunotherapy as we define key
      transcription factors and epigenetic programs underlying T cell dysfunction and
      surface markers that predict therapeutic reprogrammability.

PMID- 28514451
TI  - Structure of the full-length glucagon class B G-protein-coupled receptor.
AB  - The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled
      receptor family and plays a key role in glucose homeostasis and the
      pathophysiology of type 2 diabetes. Here we report the 3.0 A crystal structure of
      full-length GCGR containing both the extracellular domain and transmembrane
      domain in an inactive conformation. The two domains are connected by a 12-residue
      segment termed the stalk, which adopts a beta-strand conformation, instead of
      forming an alpha-helix as observed in the previously solved structure of the GCGR
      transmembrane domain. The first extracellular loop exhibits a beta-hairpin
      conformation and interacts with the stalk to form a compact beta-sheet structure.
      Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics
      studies suggest that the stalk and the first extracellular loop have critical
      roles in modulating peptide ligand binding and receptor activation. These
      insights into the full-length GCGR structure deepen our understanding of the
      signalling mechanisms of class B G-protein-coupled receptors.

PMID- 28514459
TI  - Late-Life Depression and the Prodromes of Dementia.

PMID- 28514458
TI  - Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment
      of Actinic Keratoses: A Randomized Clinical Trial.
AB  - Importance: Photodynamic therapy (PDT) is an effective and cosmetically favorable
      treatment modality for actinic keratoses (AKs). However, prolonged incubation
      times and pain associated with treatment are burdensome to the patient and a
      hindrance to widespread use of PDT as standard field therapy for AK. Objective:
      To evaluate efficacy and pain associated with microneedle expedited PDT. Design,
      Setting, and Participants: The Microneedle Photodynamic Therapy II (MNPDT-II)
      study was a randomized, single-blinded, split-face controlled, 2-arm clinical
      trial. Thirty-three participants with AK on the face were recruited in a
      university dermatology outpatient clinic from 2015 to 2016, and 32 participants
      completed the study. Interventions: Participants were randomized into 2
      incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA)
      incubation times, after pretreatment with a microneedle roller (200 um) vs a sham
      roller. They were blinded to the laterality of microneedle and sham roller
      assignments. After incubation, they were exposed to blue light (Blu-U, Dusa
      Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2. Main Outcomes
      and Measures: The primary outcome was to quantitatively measure AK resolution,
      and the secondary outcome was to assess pain associated with microneedle
      pretreatment. Results: Thirty-three individuals were recruited and randomized to
      either the 20-minute or the 10-minute incubation arm. Thirty-two participants
      completed the study with a mean follow-up time of 34.5 days in the 20-minute
      group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm,
      average AK clearance was 76% vs 58% on the sham side (P < .01), including 3
      patients with complete clearance, although not statistically significant (P =
      .25). Pain assessment on the visual analog scale (VAS) during blue light
      illumination was not significantly different between the microneedle and sham
      sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK
      clearance for the microneedle pretreated side was 43% compared with 38% on the
      sham side (P = .66). Pain during the blue light exposure was not significantly
      different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21),
      respectively. Conclusions and Relevance: Photodynamic therapy with microneedle
      pretreatment at a 20-minute ALA incubation time significantly improved AK
      clearance with efficacy similar to that of a conventional 1-hour ALA incubation
      time. The additional advantage to expedited treatment was that the procedure was
      virtually painless. However, expedited exposure of a 10-minute ALA incubation
      time did not reach significantly different AK clearance from the sham control.
      Trial Registration: clinicaltrials.gov Identifier: NCT02594644.

PMID- 28514460
TI  - Considering the Role of the Laparoscopic Adjustable Gastric Band: Do Not Throw
      the Baby Out With the Bathwater.

PMID- 28514461
TI  - Lessons to Be Learned From 22q11.2 Syndromes.

PMID- 28514462
TI  - Lessons to be Learned From 22q2.11 Syndromes-Reply.

PMID- 28514464
TI  - A Meta View on Meta-analyses.

PMID- 28514465
TI  - Bicuspid Aortopathy-Reply.

PMID- 28514466
TI  - How Microneedles Can Change Cutaneous Drug Delivery-Small Needles Make a Big
      Difference.

PMID- 28514468
TI  - Disseminated Erythematous Crusted and Pustular Plaques on the Trunk.

PMID- 28514467
TI  - Novel Deceased Donor Perfusion Model for High-Fidelity Simulation in Vascular
      Surgery.

PMID- 28514463
TI  - Pediatric Psoriasis Comorbidity Screening Guidelines.
AB  - Importance: Psoriasis is a complex inflammatory skin condition associated with
      serious medical comorbidities in adults, including obesity, hypertension,
      dyslipidemia, type 2 diabetes mellitus, psoriatic arthritis, nonalcoholic fatty
      liver disease, depression, anxiety, and decreased quality of life. Because
      psoriasis begins in childhood in almost one-third of patients, early
      identification of risk may be critical to minimizing effects on future health.
      Objective: To develop the first set of guidelines for comorbidity screening for
      patients with pediatric psoriasis based on current evidence. Evidence Review: A
      literature review was performed using PubMed from January 1999 through December
      2015. Limiting the search to human studies published in English and removing
      reviews and editorials produced 153 relevant manuscripts. An expert panel in
      psoriasis, pediatric dermatology, pediatric rheumatology, pediatric
      gastroenterology, pediatric endocrinology, and adult and pediatric cardiology
      used the patient-centered Strength of Recommendation Taxonomy (SORT) method to
      evaluate and grade the quality of evidence. Findings: Because of the limited
      number of pediatric studies published on these topics, the strength of the
      panel's recommendations is classified as SORT level C expert consensus
      recommendations. The majority of recommendations coincide with those endorsed by
      the American Academy of Pediatrics for the general pediatric patient but with
      added attention to signs and symptoms of arthritis, depression, and anxiety. The
      panel also identified key areas for further investigation. Conclusions and
      Relevance: Patients with pediatric psoriasis should receive routine screening and
      identification of risk factors for associated comorbidities. These guidelines are
      relevant for all health care providers caring for patients with pediatric
      psoriasis, including primary care clinicians, dermatologists, and pediatric
      specialists. Because these are the first pediatric guidelines, re-review and
      refinement will be necessary as studies further detail, and possibly stratify,
      risk in affected children.

PMID- 28514471
TI  - Addressing the Communication and Other Needs of Persons With Severe Disabilities
      Through Engaged Interprofessional Teams: Introduction to a Clinical Forum.
AB  - Purpose: Interprofessional collaborative practice (IPCP) is introduced as a
      viable and preferred clinical methodology for speech-language pathologists and
      others serving persons with severe disabilities. Contributions to this clinical
      forum dedicated to IPCP and severe disabilities are described. Method: This
      clinical focus article introduces IPCP and reviews literature specific to its
      origins and effectiveness, defines severe disabilities, and proposes IPCP as a
      vital tenet in effective communication-related and other service delivery for
      this population. Conclusion: IPCP is supported as a recommended practice
      methodology for speech-language pathologists and other team members providing
      services to persons with severe disabilities.

PMID- 28514472
TI  - The Trifocus Framework and Interprofessional Collaborative Practice in Severe
      Disabilities.
AB  - Purpose: Individuals with severe disabilities are a diverse group of learners
      with complex communication needs. This article presents a synthesis of the
      literature addressing the five strategies of the trifocus framework, with its
      triadic structure of learner with disability, communication partner, and
      environment. The application of interprofessional collaborative practice (IPCP)
      to the implementation of trifocus framework communication strategies is
      emphasized. Method: A literature search was conducted using Google Scholar and
      EBSCO to identify literature and research studies on IPCP and communication
      intervention for learners with severe disabilities, published 1994-2015, and then
      organized within the trifocus framework. The trifocus strategies are enhancing
      sensitivity, utilizing routines, increasing communication opportunities,
      modifying the communication environment, and augmenting input. Studies that
      included at least one participant with severe disabilities and their
      communication partners were considered. A secondary search was then conducted by
      reviewing the articles referenced in the original articles. Conclusion: Effective
      IPCP in communication intervention considers the learner's characteristics, the
      knowledge and skills required of communication partners, and effective
      environmental arrangements to support communication. Future research should
      include clear participant descriptions, documentation of fidelity measures, and
      evidence of generalization to support professionals to know when findings are
      relevant to the individuals they serve.

PMID- 28514470
TI  - Noncontact spirometry with a webcam.
AB  - We present an imaging-based method for noncontact spirometry. The method tracks
      the subtle respiratory-induced shoulder movement of a subject, builds a
      calibration curve, and determines the flow-volume spirometry curve and vital
      respiratory parameters, including forced expiratory volume in the first second,
      forced vital capacity, and peak expiratory flow rate. We validate the accuracy of
      the method by comparing the data with those simultaneously recorded with a gold
      standard reference method and examine the reliability of the noncontact
      spirometry with a pilot study including 16 subjects. This work demonstrates that
      the noncontact method can provide accurate and reliable spirometry tests with a
      webcam. Compared to the traditional spirometers, the present noncontact
      spirometry does not require using a spirometer, breathing into a mouthpiece, or
      wearing a nose clip, thus making spirometry test more easily accessible for the
      growing population of asthma and chronic obstructive pulmonary diseases.

PMID- 28514469
TI  - Association of Very Low-Volume Practice With Vascular Surgery Outcomes in New
      York.
AB  - Importance: Little research has focused on very low-volume surgery, especially in
      the context of decreasing vascular surgery volume with the adoption of
      endovascular procedures. Objective: To investigate the existence and outcomes of
      open abdominal aortic aneurysm repair (OAR) and carotid endarterectomy (CEA)
      performed by very low-volume surgeons in New York. Design, Settings, and
      Participants: This cohort study examined inpatient data of patients undergoing
      elective OAR or CEA from 2000 to 2014 from all New York hospitals. Exposures:
      Surgeons who performed 1 or less designated procedure per year on average were
      considered very low volume, as opposed to higher-volume surgeons. Main Outcomes
      and Measures: Temporal trends of the existence of very low-volume practice were
      evaluated. Hierarchical logistic regression was used to compare in-hospital
      outcomes and health care resource use between patients treated by very low-volume
      surgeons and higher-volume surgeons for both OAR and CEA, adjusting for patient,
      surgeon, and hospital characteristics. Results: There were 8781 OAR procedures
      and 68 896 CEA procedures included in the study. The mean (SD) patient age was
      71.7 (8.4) years for OAR and 71.5 (9.1) years for CEA. A total of 614 surgeons
      performed OAR and 1071 performed CEA in New York during the study period. Of
      these, 318 (51.8%) and 512 (47.8%), respectively, were very low-volume surgeons.
      Very low-volume surgeons were less likely to be vascular surgeons. The number and
      proportion of very low-volume surgeons decreased over years. Compared with
      patients treated by higher-volume surgeons, those treated by very low-volume
      surgeons were more likely to have higher in-hospital mortality (odds ratio [OR],
      2.09; 95% CI, 1.41-3.08) following OAR and higher risks of postoperative
      myocardial infarction (OR, 1.83; 95% CI, 1.03-3.26) and stroke (OR, 1.78; 95% CI,
      1.21-2.62) following CEA. Patients treated by very low-volume surgeons also had
      greater health care resource use following both surgeries, including prolonged
      length of stay (OR, 1.37; 95% CI, 1.11-1.70) following OAR as well as higher
      charges (OR, 1.28; 95% CI, 1.01-1.62) and increased 30-day readmission (OR, 1.30;
      95% CI 1.04-1.62) following CEA. Conclusions and Relevance: The OAR and CEA
      procedures performed by very low-volume surgeons resulted in worse postoperative
      outcomes and greater lengths of stay. Although the percentage of very low-volume
      surgeons declined from 2000 to 2014, it remains concerning, given ready access to
      higher-volume surgeons. Future research is needed to understand the existence of
      this practice pattern in other surgical fields. Efforts to eliminate this
      practice pattern are warranted to ensure high-quality care for all patients.

PMID- 28514473
TI  - Effective Team Practices: Interprofessional Contributions to Communication Issues
      With a Parent's Perspective.
AB  - Purpose: This clinical focus article contains a detailed description of how to
      build effective teams that use interprofessional collaborative practice (IPCP)
      with special-education professionals, speech-language pathologists, and families
      of children with severe disabilities. Method: This clinical focus article
      provides information on using the essential elements of team building and IPCP to
      provide quality care to families who have children with severe disabilities. The
      6 essential elements for team building are described, with suggestions for
      including families in each: goal-setting, roles and responsibilities, effective
      and efficient process, communication and interpersonal relationships,
      collaborative problem solving, and evaluation. The 4 competency domains of IPCP
      are embedded into each of the team-building elements to demonstrate how teams can
      implement IPCP. Results: A case study illustrates the difficulty one parent
      experienced working with a team across the 6 essential team-building elements
      when seeking communication services for her child with severe disabilities.
      Conclusions: Building teams with IPCP can be effective for including families and
      creating high-quality outcomes for individuals with severe disabilities.

PMID- 28514475
TI  - Cotreatment as a Vehicle for Interprofessional Collaborative Practice: Physical
      Therapists and Speech-Language Pathologists Collaborating in the Care of Children
      With Severe Disabilities.
AB  - Purpose: This article defines interprofessional collaborative practice and links
      its key features with accepted practice conceptualizations of physical therapy.
      Cotreatment with speech-language pathology is described as a vehicle for
      interprofessional collaborative practice for children with severe disabilities.
      Method: The article reviews the International Classification of Functioning,
      Disability, and Health (WHO, 2015) and the Hypothesis-Oriented Algorithm for
      Clinicians II (Rothstein, Echternach, & Riddle, 2003) as existing service
      delivery frameworks in physical therapy and discusses how interprofessional
      collaborative practice between speech-language pathologists and physical
      therapists can be useful within these practice guidelines. Results: A case
      illustration featuring interprofessional collaborative practice during
      cotreatment for a child with severe disabilities through physical therapy and
      speech-language pathology showed more seamless care and better progress in the
      pursuit of three main goals: physical movement, communication of needs, and
      participation in classroom activities. Conclusions: Interprofessional
      collaborative practice is supported as a recommended practice methodology for
      physical therapists and speech-language pathologists serving persons with severe
      disabilities.

PMID- 28514474
TI  - Comprehensive Literacy Instruction, Interprofessional Collaborative Practice, and
      Students With Severe Disabilities.
AB  - Purpose: The purpose of this clinical focus article is to briefly describe
      comprehensive emergent and conventional literacy instruction for students with
      severe disabilities. Specific attention is given to interprofessional
      collaborative practice and the roles of team members in planning and delivering
      instruction. Method: A rationale for the delivery of comprehensive instruction
      that balances skill and meaning emphases is provided with reference to new
      college and career readiness standards, the literature on literacy acquisition
      for students without disabilities, and, when possible, the literature on literacy
      acquisition for students with severe disabilities. Specific instructional
      approaches are presented to demonstrate how teams can actively engage students
      with severe disabilities in instruction that is collaborative, participatory, and
      interactive. Results/Conclusions: Successful provision of comprehensive literacy
      instruction that allows students with severe disabilities to achieve conventional
      literacy takes time and the efforts of a collaborative interprofessional team.
      Speech-language pathologists play a critical role on these teams as they ensure
      that students with severe disabilities have the language and communication
      supports they need to be successful.

PMID- 28514476
TI  - Mary's Case: An Illustration of Interprofessional Collaborative Practice for a
      Child With Severe Disabilities.
AB  - Purpose: The principles of interprofessional collaborative practice (IPCP) are
      illustrated through the case of Mary, a child with severe disabilities. Method:
      Mary's experiences from early childhood to young adulthood are highlighted by
      both optimal and less-than-ideal examples of clinical services and collaborative
      practice. The range of collaboration illustrates potential variations in service
      delivery. Thematic comments and resources are provided by professionals
      experienced with and committed to IPCP who represent the following four
      disciplines: occupational therapy, physical therapy, special education, and
      speech-language pathology. Conclusions: Although potentially challenging, IPCP is
      a dynamic practice methodology appropriate for speech-language pathologists and
      others serving persons with severe disabilities.

PMID- 28514481
TI  - Outside the Door.

PMID- 28514478
TI  - Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year
      Follow-up Study.
AB  - Importance: Neuropsychiatric symptoms, depressive symptoms in particular, are
      common in patients with dementia but whether depressive symptoms in adulthood
      increases the risk for dementia remains the subject of debate. Objective: To
      characterize the trajectory of depressive symptoms over 28 years prior to
      dementia diagnosis to determine whether depressive symptoms carry risk for
      dementia. Design, Setting, and Participants: Up to 10 308 persons, aged 35 to 55
      years, were recruited to the Whitehall II cohort study in 1985, with the end of
      follow-up in 2015. Data analysis for this study in a UK general community was
      conducted from October to December 2016. Exposures: Depressive symptoms assessed
      on 9 occasions between 1985 and 2012 using the General Health Questionnaire. Main
      Outcomes and Measures: Incidence of dementia (n = 322) between 1985 and 2015.
      Results: Of the 10 189 persons included in the study, 6838 were men (67%) and
      3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow
      up, 27 years) did not have significantly increased risk for dementia (hazard
      ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for
      sociodemographic covariates, health behaviors, and chronic conditions. However,
      those with depressive symptoms in 2003 (mean follow-up, 11 years) had an
      increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring
      depressive symptoms (>=2 of 3 occasions) in the early study phase (mean follow
      up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those
      with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did
      have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of
      retrospective depressive trajectories over 28 years, using mixed models and a
      backward time scale, shows that in those with dementia, differences in depressive
      symptoms compared with those without dementia became apparent 11 years
      (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and
      became more than 9 times larger at the year of diagnosis (difference, 5.81; 95%
      CI, 4.81-6.81; P < .001). Conclusions and Relevance: Depressive symptoms in the
      early phase of the study corresponding to midlife, even when chronic/recurring,
      do not increase the risk for dementia. Along with our analysis of depressive
      trajectories over 28 years, these results suggest that depressive symptoms are a
      prodromal feature of dementia or that the 2 share common causes. The findings do
      not support the hypothesis that depressive symptoms increase the risk for
      dementia.

PMID- 28514482
TI  - Breast Cancer Genetic Testing Among African Patients With Breast Cancer:
      Deoxyribonucleic Acid Extraction From Tumor Tissue and International
      Multidisciplinary Partnerships.

PMID- 28514485
TI  - Occurrence of Acute Cerebellar Syndrome After Topical Application of
      Fluorouracil.

PMID- 28514486
TI  - Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic
      Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the
      Meta-analytic Evidence.
AB  - Importance: Limited treatment responses in schizophrenia prompted the testing of
      combining an antipsychotic drug treatment with a second psychotropic medication.
      A comprehensive evaluation of the efficacy of multiple medication combinations is
      missing. Objective: To summarize and compare the meta-analytically determined
      efficacy of pharmacologic combination strategies of antipsychotic drugs in adults
      with schizophrenia. Data Sources: Systematic search of PubMed and PsycInfo until
      May 13, 2016. Study Selection: Meta-analyses of randomized clinical trials
      comparing the efficacy of antipsychotic drugs combined with other antipsychotic
      or nonantipsychotic medications vs placebos or antipsychotic monotherapy among
      adults with schizophrenia. Data Extraction and Synthesis: Independent reviewers
      extracted the data and assessed the quality of the methods of the included meta
      analyses using A Measurement Tool to Assess Systematic Reviews (AMSTAR), adding 6
      new items to rate their quality. Effect sizes, expressed as standardized mean
      difference /Hedges g or risk ratio, were compared separately for combinations
      with any antipsychotic drug and for combinations with clozapine. Main Outcomes
      and Measures: The primary outcome was total symptom reduction. Secondary outcomes
      included positive and negative symptoms, treatment recommendations by authors,
      study-defined inefficacies, cognitive and depressive symptoms, discontinuation of
      treatment because of any cause, and inefficacies or intolerabilities. Results: Of
      3397 publications, 29 meta-analyses testing 42 combination strategies in 381
      individual trials and among 19 833 participants were included. For total symptom
      reductions, 32 strategies that augmented any antipsychotic drug and 5 strategies
      that augmented clozapine were examined. Fourteen combination treatments
      outperformed controls (standard mean difference/Hedges g, -1.27 [95% CI, -2.35 to
      -0.19] to -0.23 [95% CI, -0.44 to -0.02]; P = .05). No combination strategies
      with clozapine outperformed controls. The quality of the methods of the meta
      analyses was generally high (mean score, 9 of a maximum score of 11) but the
      quality of the meta-analyzed studies was low (mean score, 2.8 of a maximum score
      of 8). Treatment recommendations correlated with the effect size (correlation
      coefficient, 0.22; 95% CI, 0.35-0.10; P < .001), yet effect sizes were inversely
      correlated with study quality (correlation coefficient, -0.06; 95% CI, 0.01 to 
      0.12; P = .02). Conclusions and Relevance: Meta-analyses of 21 interventions
      fully or partially recommended their use, with recommendations being positively
      correlated with the effect sizes of the pooled intervention. However, the effect
      sizes were inversely correlated with meta-analyzed study quality, reducing
      confidence in these recommendations. Higher-quality trials and patient-based meta
      analyses are needed to determine whether subpopulations might benefit from
      combination treatment, as no single strategy can be recommended for patients with
      schizophrenia based on the current meta-analytic literature.

PMID- 28514488
TI  - Optimal vs Feasible Volume Thresholds in Vascular Surgery.

PMID- 28514489
TI  - Nerve Conduction Studies for Carpal Tunnel Syndrome: Gold Standard or Unnecessary
      Evil?

PMID- 28514487
TI  - Reoperation and Medicare Expenditures After Laparoscopic Gastric Band Surgery.
AB  - Importance: Following the US Food and Drug Administration approval for
      laparoscopic gastric band surgery in 2001, as many as 96 000 devices have been
      placed annually. The reported rates of reoperation range from 4% to 60% in short
      term studies; however, to our knowledge, few long-term population-level data on
      outcomes or expenditures are known. Objective: To describe the rate of device
      related reoperations occurring after laparoscopic gastric band surgery as well as
      the associated payments in a longitudinal national cohort. Design, Settings, and
      Participants: This retrospective review of 25 042 Medicare beneficiaries who
      underwent gastric band placement between 2006 and 2013 identifies gastric band
      related reoperations, including device removal, device replacement, or revision
      to a different bariatric procedure (eg, a gastric bypass or sleeve gastrectomy).
      The rates of reoperation were risk adjusted using a multivariable logistic
      regression model that included patient age, sex, race/ethnicity, Elixhauser
      comorbidities, and the year that the operation was performed. Main Outcomes and
      Measures: Rate of device-related reoperation nationally and across individual
      hospital referral regions. Thirty-day total episode Medicare payments to
      hospitals for the index operation and any subsequent reoperations. Results: Of
      the 25 042 patients who underwent gastric band placement, 20 687 (82.61%) were
      white, 18 143 (72.45%) were women, and the mean age was 57.56 years. Patients
      (mean age, 57.5; 76.2% women) requiring reoperation had lower rates of
      hypertension (64.9% vs 73.4%; P < .001) and diabetes (40.4% vs 44.6%; P < .001)
      and were more likely to have their index operation at a for-profit hospital
      (34.6% vs 22.0%; P < .001). With an average of 4.5-year follow-up, 4636 patients
      (18.5%) underwent 17 539 reoperations (an average of 3.8 procedures/patient).
      Hospital referral regions demonstrated a 2.9-fold variation in risk- and
      reliability-adjusted rates of reoperation (lower quartile average, 13.3%; upper
      quartile average, 39.1%). During the study period, Medicare paid $470 million for
      laparoscopic gastric band associated procedures, of which $224 million (47.6%) of
      the payments were for reoperations. From 2006 to 2013, the proportion of payments
      from Medicare for reoperations increased from 16.4% to 77.3% of their annual
      spending on the gastric band device. Conclusions and Relevance: Among Medicare
      beneficiaries undergoing gastric band surgery, device-related reoperation was
      common, costly, and varied widely across hospital referral regions. These
      findings suggest that payers should reconsider their coverage of the gastric band
      device.

PMID- 28514490
TI  - Brain ultrasound rehearsal before surgery: A pilot cadaver study.
AB  - It has been shown that brain ultrasonography (US) is an efficient tool for
      improving three-dimensional (3D) spatial orientation during neurosurgical
      interventions. However, it necessitates specific training as it is highly
      operator-dependent. To date, neurosurgeons have relied solely on intraoperative
      practice to improve their mastery of brain US; this has obvious limitations.
      Herein, we consider whether a study of brain US on human cadavers could enable a
      training platform for neurosurgeons and residents to be developed. Standard two
      dimensional (2D) brain US was performed on two human cadavers (one fresh-frozen
      and one Thiel-prepared) through left frontoparietal, left frontal, right
      temporal, and left parietal craniotomies. US workflow and image quality were
      assessed in both preparations. It was possible to assess US in both cadaver
      preparations; however, the specimen prepared with Thiel-fixation performed
      better, with superior image quality and specimen usability at room temperature.
      US images were obtainable through all surgical corridors with the main
      intracranial anatomical landmarks easily identifiable. US of cadaveric brains is
      feasible and delivers good quality results. This technique could allow
      neurosurgeons to develop the expertise required for a successful clinical
      application preoperatively. Clin. Anat. 30:1017-1023, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28514492
TI  - Ordering by the numbers in anatomy and by letters Too.
AB  - Here, new rules of Latin anatomical nomenclature are proposed to deal with cases
      not covered by existing or other recommended rules. Determiners (e.g., numerals,
      letters, alphanumeric strings, and Latin names of Greek letters) should follow
      the noun they specify or limit, just as it is recommended that adjectives should
      follow the noun they modify. In general, Roman numerals, Latin letters, and Latin
      names of Greek letters are preferable to Arabic numerals and Greek letters in
      Latin anatomical terms. It is also noted that the word typus (type) appears to be
      superfluous and unnecessary in the Latin anatomical nomenclature. Clin. Anat.
      30:700-702, 2017. (c) 2017Wiley Periodicals, Inc.

PMID- 28514491
TI  - 3D image-based morphometric analysis of the scapular neck length in subjects
      undergoing reverse shoulder arthroplasty.
AB  - Scapular notching after RSA may, in part, be related to a patient's scapular
      morphology. The purpose of this study was to develop a novel 3 D measurement
      technique to describe infraglenoid tubercle morphometry. We hypothesize that the
      parameters describing infraglenoid tubercle would be normally distributed and
      would correlate with individual's demographics and glenoid morphometry. A group
      of 110 subjects treated with RSA were evaluated. Scapular geometry was obtained
      from pre-operative CT scans. The scapular neck length was defined in anterior and
      posterior view as the orthogonal distance between the glenoid surface and (a) the
      point of most significant change of curvature on lateral pillar; (b) the most
      lateral portion of the infraglenoid tubercle. Scapular neck angle, maximum
      anatomical adduction angle, glenoid width, height and version were also measured.
      Scapular neck length measured in the anterior and posterior view were normally
      distributed with mean values of 17.6 +/- 2.8 mm and 7.9 +/- 2.5 mm, respectively.
      Scapular neck angle was on average 112.4 +/- 10.6 degrees  and maximal adduction
      angle was 17.6 +/- 2.8 degrees . No significant associations between infraglenoid
      tubercle morphometric parameters, demographic, glenoid size or version were
      identified. Improved understanding of the patient-specific risk factors for
      scapular notching will help surgeons with pre-surgical planning and implant
      selection. Parametrization of the infraglenoid tubercle presented in this study
      showed normal distribution in the population unrelated to gender, side or
      demographics. The size of the infraglenoid tubercle is a unique trait, pre
      operative evaluation of the scapular neck should be always warranted to decrease
      the incidence of post-operative notching. Clin. Anat. 31:43-55, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28514493
TI  - The Narrow Road to the Deep Past: In Search of the Chemistry of the Origin of
      Life.
AB  - The sequence of events that gave rise to the first life on our planet took place
      in the Earth's deep past, seemingly forever beyond our reach. Perhaps for that
      very reason the idea of reconstructing our ancient story is tantalizing, almost
      irresistible. Understanding the processes that led to synthesis of the chemical
      building blocks of biology and the ways in which these molecules self-assembled
      into cells that could grow, divide and evolve, nurtured by a rich and complex
      environment, seems at times insurmountably difficult. And yet, to my own
      surprise, simple experiments have revealed robust processes that could have
      driven the growth and division of primitive cell membranes. The nonenzymatic
      replication of RNA is more complicated and less well understood, but here too
      significant progress has come from surprising developments. Even our efforts to
      combine replicating compartments and genetic materials into a full protocell
      model have moved forward in unexpected ways. Fortunately, many challenges remain
      before we will be close to a full understanding of the origin of life, so the
      future of research in this field is brighter than ever!

PMID- 28514494
TI  - Covalent Protein Labeling by SpyTag-SpyCatcher in Fixed Cells for Super
      Resolution Microscopy.
AB  - Labeling proteins with high specificity and efficiency is a fundamental
      prerequisite for microscopic visualization of subcellular protein structures and
      interactions. Although the comparatively small size of epitope tags makes them
      less perturbative to fusion proteins, they require the use of large antibodies
      that often limit probe accessibility and effective resolution. Here we use the
      covalent SpyTag-SpyCatcher system as an epitope-like tag for fluorescent labeling
      of intracellular proteins in fixed cells for both conventional and super
      resolution microscopy. We also applied this method to endogenous proteins by gene
      editing, demonstrating its high labeling efficiency and capability for isoform
      specific labeling.

PMID- 28514495
TI  - Protective effects of dioscin against cisplatin-induced nephrotoxicity via the
      microRNA-34a/sirtuin 1 signalling pathway.
AB  - BACKGROUND AND PURPOSE: Dioscin exhibits a range of pharmacological actions but
      little is known of its effects on cisplatin (CDDP)-induced nephrotoxicity. Here,
      we have assessed the effects and the possible mechanisms of dioscin against CDDP
      induced nephrotoxicity. EXPERIMENTAL APPROACH: We used an in vivo model of CDDP
      induced nephrotoxicity in rats and mice and, in vitro, cultures of NRK-52E and HK
      2 cells. The dual luciferase reporter assay was used to demonstrate modulation,
      by dioscin, of the targeting of sirtuin 1 (Sirt1) by microRNA (miR)-34a.
      Molecular docking assays were used to analyse the effects of dioscin with Sirt1,
      Keap1 and NF-kappaB. KEY RESULTS: Dioscin attenuated cell damage in vitro and
      decreased renal injury in rats and mice, treated with CDDP. In terms of
      mechanisms, dioscin reversed CDDP-induced up-regulation of miR-34a and thus up
      regulated Sirt1 levels. In addition, dioscin altered levels of haem oxygenase 1,
      glutathione-cysteine ligase subunits (GCLC, GCLM) and Keap1, along with increased
      nuclear translocation of Nrf2, thus decreasing oxidative stress. Also, dioscin
      affected levels of AP-1, COX-2, HMGB1, IkappaB-alpha, IL-1beta, IL-6 and TNF
      alpha and decreased the ratio of acetylated NF-kappaB and normal NF-kappaB, to
      suppress inflammation. From molecular docking assays, dioscin directly bound to
      Sirt1, Keap1 and NF-kappaBp65 by hydrogen bonding and/or hydrophobic
      interactions. CONCLUSIONS AND IMPLICATIONS: Our results have linked CDDP-induced
      nephrotoxicity and the miR-34a/Sirt1 signalling pathway, which was modulated by
      dioscin. This natural product could be developed as a new candidate to alleviate
      CDDP-induced renal injury.

PMID- 28514496
TI  - A reappraisal of pediatric thoracic surface anatomy.
AB  - Accurate knowledge of surface anatomy is fundamental to safe clinical practice. A
      paucity of evidence in the literature regarding thoracic surface anatomy in
      children was identified. The associations between surface landmarks and internal
      structures were meticulously analyzed by reviewing high quality computed
      tomography (CT) images of 77 children aged from four days to 12 years. The
      results confirmed that the sternal angle is an accurate surface landmark for the
      azygos-superior vena cava junction in a plane through to the level of upper T4
      from birth to age four, and to lower T4 in older children. The concavity of the
      aortic arch was slightly below this plane and the tracheal and pulmonary artery
      bifurcations were even lower. The cardiac apex was typically at the 5th
      intercostal space (ICS) from birth to age four, at the 4th ICS and 5th rib in 4
      12 year olds, and close to the midclavicular line at all ages. The lower border
      of the diaphragm was at the level of the 6th or 7th rib at the midclavicular
      line, the 7th ICS and 8th rib at the midaxillary line, and the 11th thoracic
      vertebra posteriorly. The domes of the diaphragm were generally flatter and lower
      in children, typically only one rib level higher than its anterior level at the
      midclavicular line. Diaphragm apertures were most commonly around the level of
      T9, T10, and T11 for the IVC, esophagus and aorta, respectively. This is the
      first study to provide an evidence-base for thoracic surface anatomy in children.
      Clin. Anat. 30:788-794, 2017. (c) 2017Wiley Periodicals, Inc.

PMID- 28514497
TI  - Does mutational analysis influence the management of differentiated thyroid
      cancers?

PMID- 28514498
TI  - Decreased bed rest post-percutaneous coronary intervention with a 7-French
      arterial sheath and its effects on vascular complications.
AB  - AIMS AND OBJECTIVES: To compare the incidence of femoral access puncture site
      complications in the control group, who underwent 6 hr of bed rest, with patients
      in the case group, who underwent 4 hr of bed rest. BACKGROUND: The ideal bed rest
      length after percutaneous coronary intervention with a 7-French arterial sheath
      has been investigated by nursing practice. However, in this larger-sheath-size
      group, best practices have not been determined, and bed rest time continues to
      vary markedly among institutions. DESIGN: Retrospective study. METHODS: Data were
      retrieved from the National Cardiovascular Data Registry and electronic health
      records in this retrospective study. Sample size was 401 patients: 152 case
      patients with 4-hr bed rest and 249 controls with 6-hr bed rest. Case group data
      were obtained from 20 May 2013-31 December 2014; and control group data, 15 June
      2011-20 May 2013. RESULTS: National Cardiovascular Data Registry event rates were
      generally low in both groups: Only three patients in each group had a bleeding
      event within 72 hr (2% vs. 1%) and no patient and only two controls had
      arteriovenous fistula (0% vs. 1%). Complications documented in the electronic
      health records with institutional femoral access puncture site complication
      definitions identified bleeding at the access site in eight case patients (5%)
      and nine controls (4%). Haematoma at the access site occurred in 21 case patients
      (14%) and 25 controls (10%). CONCLUSIONS: The practice change of decreasing bed
      rest from 6-4 hr for patients with 7-French arterial sheaths post-percutaneous
      coronary intervention was associated with no significant change in femoral access
      puncture site complications in either National Cardiovascular Data Registry data
      or institutional electronic health records data. RELEVANCE TO CLINICAL PRACTICE:
      This introduces expanded evidence of safety in decreasing bed rest length in
      larger (7-French) arterial sheaths post-percutaneous coronary intervention.

PMID- 28514499
TI  - Surface anatomy of major anatomical landmarks of the neck in an adult population:
      A Ct Evaluation of Vertebral Level.
AB  - To compare the projectional surface anatomy of healthy individuals in an adult
      population with those with a thyroid mass, using computed tomography (CT).
      Sixteen slice CT images of 101 individuals were analyzed using a 32-bit Radiant
      DICOM viewer to establish the relationships among major anatomical landmarks in
      the neck and their vertebral levels. The structures investigated included: hard
      palate (HP), hyoid bone (HB) including body and lesser horns, soft palate (SP),
      thyroid gland (TG) (both superior and inferior poles), thyroid gland
      anteroposterior (APD) and superoinferior (SID) diameters, thyroid isthmus (TI)
      superoinferior dimension, epiglottis, vertebral arteries (right and left), and
      both right and left parotid glands (superior and inferior extents). The vertebral
      levels noted most frequently were: body of hyoid bone (C4, 42.71%); lesser horns
      of hyoid bone (C3, 36.46%); thyroid gland superior pole (C6, 31.25%); and thyroid
      gland inferior pole (T2, 30.2%). TG-ID, TG-APD, and TG-SID were not significantly
      different between males and females in the healthy group; however, there was a
      significant gender difference in thyroid gland inferior diameter in the pathology
      group [males 2.16(+/-1.16) vs. females 3.37(+/-1.30), P = 0.01, paired sample t
      test]. Further studies are needed to determine whether neck pathology in those
      with a thyroid mass affects the dimensions of the thyroid gland. Moreover, the
      surface anatomy of the neck should be revisited using modern imaging techniques
      to address inconsistencies in anatomy and clinical reference texts. Clin. Anat.
      30:781-787, 2017. (c) 2017Wiley Periodicals, Inc.

PMID- 28514500
TI  - Histology of the distal dural ring.
AB  - The distal dural ring (DDR) is a conserved intracranial anatomic structure
      marking the boundary point at which the internal carotid artery (ICA) exits the
      cavernous sinus (CS) and enters the subarachnoid space. Although the CS has been
      well described in a range of anatomic studies, to our knowledge no prior study
      has analyzed the histologic relationship between the ICA and DDR.
      Correspondingly, our objective was to assess the relationship of the DDR to the
      ICA and determine whether the DDR can be dissected from the ICA and thus divided,
      or can only be circumferentially trimmed around the artery. The authors examined
      ten fresh-frozen, adult cadaveric specimens. A standard frontotemporal
      craniotomy, orbito-optic osteotomy, and extradural anterior clinoidectomy was
      performed bilaterally. The cavernous ICA, DDR, and supraclinoid ICA were
      harvested as an en bloc specimen. Specimens formalin-fixed and paraffin-embedded
      prior to routine histochemical staining with hematoxylin and eosin and Masson
      trichrome. In all specimens, marked microscopic investment of the DDR throughout
      the ICA adventitia was noted. Dural collagen fibers extensively permeated the
      arterial layers superficial to the muscularis propria, with no evidence of a
      clear separation between the DDR and arterial adventitia. Histologic analysis
      suggests that the ICA and DDR are highly interrelated, continuous structures, and
      therefore attempted intraoperative dissection between these structures may carry
      an elevated risk of injury to the ICA. We correspondingly recommend careful
      circumferential trimming of the DDR in lieu of direct dissection in cases
      requiring mobilization of the clinoidal ICA. Clin. Anat. 30:742-746, 2017. (c)
      2017Wiley Periodicals, Inc.

PMID- 28514501
TI  - Intra-articular capacity of the elbow joint.
AB  - The intra-articular capacity of the elbow joint is reported to be 23 +/- 4 ml on
      cadaveric elbows. During years, this value was the standard. The aim of this
      observational study was to reanalyze the volume of the elbow joint on live
      patients. Measurement of the intra-articular capacity and pressure of the elbow
      joint was performed on 30 patients (mean age: 43.8 years) undergoing elbow
      arthroscopy. Intra-articular capacity was recorded when the elbow moved to the
      maximum lose packed position and/or when there was a sudden drop in pressure,
      indicating a capsular rupture (maximum capacity). Indications for arthroscopy
      were loose bodies, osteoarthritis, synovitis, radial head resection, and lateral
      collateral ligament repair. Mean intra-articular capacity and pressure were 35.8
      ml and 557.5 mm Hg, respectively. Mean maximal capacity was 40.5 ml. We conclude
      that the intra-articular capacity of the elbow joint is substantially greater
      than reported in previous studies. Clin. Anat. 30:795-798, 2017. (c) 2017Wiley
      Periodicals, Inc.

PMID- 28514503
TI  - Slicing Diamond for More sp3 Group 14 Allotropes Ranging from Direct Bandgaps to
      Poor Metals.
AB  - Considerable interest in novel Si allotropes has led to intense investigation of
      tetrahedral framework structures during the last years. Recently, a guide to
      deriving sp3 -Si allotropes from atom slabs of the diamond structure enabled a
      systematic deduction of several low-density modifications. Some of the Si
      networks were recognized as experimentally known frameworks, that is, so-called
      "chemi-inspired" structures. Herein we present nine novel Si networks obtained by
      modifying three-atom-thick slabs of a cubic diamond structure after smooth
      distortion by applying the same construction kit. Analysis of the structure
      property relationships of these frameworks by using quantum-chemical methods
      shows that several of them possess direct bandgaps in the range suitable for
      light conversion. The construction kit was also applied to higher group 14
      homologues Ge and Sn, and revealed interesting differences in the band structures
      and relative energies of the homologues. A new modification of Sn was identified
      as a poor metal, which denoted significant covalent-bond characteristics.

PMID- 28514504
TI  - An anatomical variation of the eminentia hypothenaris.

PMID- 28514502
TI  - Structural and functional characteristics of oestrogen receptor beta splice
      variants: Implications for the ageing brain.
AB  - Oestrogen receptor (ER)beta is a multifunctional nuclear receptor that mediates
      the actions of oestrogenic compounds. Despite its well defined role in mediating
      the actions of oestrogens, a substantial body of evidence demonstrates that
      ERbeta has a broad range of physiological functions independent of those normally
      attributed to oestrogen signalling. These functions can partly be achieved by the
      activity of several alternatively spliced isoforms that have been identified for
      ERbeta. This short review describes structural differences between the ERbeta
      splice variants that are known to be translated into proteins. Moreover, we
      discuss how these alternative structures contribute to functional differences in
      the context of both healthy and pathological conditions. Our review also
      describes the principal factors that regulate alternative RNA splicing. The
      alternatively spliced isoforms of ERbeta are differentially expressed according
      to brain region, age and hormonal milieu, emphasising the likelihood that there
      are precise cell-specific mechanisms regulating ERbeta alternative splicing.
      However, despite these correlative data, the molecular factors regulating
      alternative ERbeta splicing in the brain remain unknown. We also review the basic
      mechanisms that regulate alternative RNA splicing and use that framework to make
      logical predictions about ERbeta alternative splicing in the brain.

PMID- 28514505
TI  - The trajectory of experience of critical care nurses in providing end-of-life
      care: A qualitative descriptive study.
AB  - AIMS AND OBJECTIVES: To understand the perceptions of critical care nurses
      towards providing end-of-life care. BACKGROUND: There has been an increasing
      interest in end-of-life care in the critical care setting. In Singapore,
      approximately half of deaths in the hospital occur during critical care. While
      nurses are well positioned to provide end-of-life care to patients and their
      family members, they faced barriers to providing end-of-life care. Also,
      providing end-of-life care has profound positive and negative psychological
      effects on nurses, with the latter being more prominent. DESIGN: Qualitative
      descriptive design. METHOD: Data collection was performed in a medical intensive
      care unit of a public tertiary hospital in Singapore. Ten registered nurses were
      purposively sampled and interviewed individually using a semi-structured
      interview guide. A codebook was developed to guide coding, and data were
      thematically analysed. Rigour was maintained. RESULTS: Nurses went through a
      trajectory of experience. They experienced the culture of care and developed
      dissatisfaction with it. The tension shaped their perception and meaning of life
      and death, and they developed mechanisms to reach resolution. CONCLUSION: This
      study provides insight on nurses' perception as a trajectory of experience and
      raised several implications on clinical practice, policy and research. There is a
      need to alleviate the tension nurses face and to facilitate coming to terms with
      the tension by improving the culture of care and supporting nurses. RELEVANCE TO
      CLINICAL PRACTICE: Nurses could be involved more in decision-making and empowered
      to start end-of-life care conversations within the team and with family members.
      Communication with family members and between nurses and doctors could be
      improved. Support for nurses providing end-of-life care could be enhanced through
      promoting social networks, education and bereavement support. Further research is
      needed to explore ways to support and empower nurses to provide end-of-life care
      in critical care.

PMID- 28514507
TI  - Hydrogen Bonds Involving Cavity NH Protons Drives Supramolecular Oligomerization
      of Amido-Corroles.
AB  - trans-A2 B-Corroles with amide substituents at different positions versus the
      macrocyclic core have been synthesized. Their self-organizing properties have
      been comprehensively evaluated both in solid-state and in solution. The rigid
      arrangement of the amide functionality with the corrole ring led to the formation
      of strong intramolecular interactions and precluded intermolecular interactions.
      Replacement of sterically hindered C6 F5 substituents at positions 5 and 15 with
      smaller electron-withdrawing CO2 Me groups resulted in significant changes in the
      self-assembly pattern. With these substituents, tetramers formed in a crystalline
      state, in which one of the H-pyrrole subunits is out of the corrole plane. This
      allows the N-H group to form a hydrogen bond with a neighboring carbonyl group of
      the n-butyl amide fragment. DOSY NMR studies showed that amido-corroles bearing
      the OCH2 CONHnBu motif formed dimers in millimolar solutions in nonpolar solvents
      and the dimers existed in equilibrium with monomers. However, the corroles
      possessing meso-ester groups did not form dimers in polar tetrahydrofuran.
      Comprehensive optical studies allowed the absorption and emission features of the
      monomer corroles to be characterized in dilute solutions.

PMID- 28514506
TI  - Human Adipose-Derived Mesenchymal Stem Cell-Secreted CXCL1 and CXCL8 Facilitate
      Breast Tumor Growth By Promoting Angiogenesis.
AB  - Autologous adipose tissue or adipose tissue with additive adipose-derived
      mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast
      cancer patients who undergo mastectomy. ADSCs play an important role in the
      angiogenesis and adipogenesis, which make it much better than other materials.
      However, ADSCs may promote residual tumor cells to proliferate or metastasize,
      and the mechanism is still not fully understood. In this study, we demonstrated
      that human ADSCs (hADSCs) could facilitate tumor cells growth after co-injection
      with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but
      hADSCs showed limited effect on the growth of MDA-MB-231 BCCs. Intriguingly,
      compared with ZR-75-30 tumor cells, MCF7 tumor cells were more potentially
      promoted by hADSCs in the aspects of angiogenesis and proliferation. Consistent
      with this, cytokine and angiogenesis array analyses showed that after co
      injection with hADSCs, the CXCL1 and CXCL8 concentration were significantly
      increased in MCF7 tumor, but only moderately increased in ZR-75-30 tumor and did
      not increase in MDA-MB-231 tumor. Furthermore, we found that CXCL1/8 were mainly
      derived from hADSCs and could increase the migration and tube formation of human
      umbilical vein endothelial cells (HUVECs) by signaling via their receptors CXCR1
      and CXCR2. A CXCR1/2-specific antagonist (SCH527123) attenuated the angiogenesis
      and tumor growth in vivo. Our findings suggest that CXCL1/8 secreted by hADSCs
      could promote breast cancer angiogenesis and therefore provide better
      understanding of safety concerns regarding the clinical application of hADSCs and
      suggestion in further novel therapeutic options. Stem Cells 2017;35:2060-2070.

PMID- 28514508
TI  - Methadone for neuropathic pain in adults.
AB  - BACKGROUND: This review replaces an earlier review, "Methadone for chronic non
      cancer pain in adults". This review serves to update the original and includes
      only studies of neuropathic pain. Methadone belongs to a class of analgesics
      known as opioids, that are considered the cornerstone of therapy for moderate-to
      severe postsurgical pain and pain due to life-threatening illnesses; however,
      their use in neuropathic pain is controversial. Methadone has many
      characteristics that differentiate it from other opioids, which suggests that it
      may have a different efficacy and safety profile. OBJECTIVES: To assess the
      analgesic efficacy and adverse events of methadone for chronic neuropathic pain
      in adults. SEARCH METHODS: We searched the following databases: CENTRAL (CRSO),
      MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also
      searched the reference lists of retrieved articles. The date of the most recent
      search was 30 November 2016. SELECTION CRITERIA: We included randomised, double
      blind studies of two weeks' duration or longer, comparing methadone (in any dose,
      administered by any route, and in any formulation) with placebo or another active
      treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures expected by Cochrane. Two review authors
      independently considered trials for inclusion in the review, assessed risk of
      bias, and extracted data. There were insufficient data to perform pooled
      analyses. We assessed the overall quality of the evidence for each outcome using
      GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included three
      studies, involving 105 participants. All were cross-over studies, one involving
      19 participants with diverse neuropathic pain syndromes, the other two involving
      86 participants with postherpetic neuralgia. Study phases ranged from 20 days to
      approximately eight weeks. All administered methadone orally, in doses ranging
      from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also
      included morphine and tricyclic antidepressants.The included studies had several
      limitations related to risk of bias, particularly incomplete reporting, selective
      outcome reporting, and small sample sizes.There were very limited data for our
      primary outcomes of participants with at least 30% or at least 50% pain relief.
      Two studies reported that 11/29 participants receiving methadone achieved 30%
      pain relief versus 7/29 participants receiving placebo. Only one study presented
      data in a manner that allowed us to calculate the number of participants with at
      least 50% pain relief. None of the 19 participants achieved a 50% reduction in
      pain intensity, either when receiving methadone or when receiving placebo. No
      study provided data for our other primary outcomes of Patient Global Impression
      of Change scale (PGIC) much or very much improved (equivalent to at least 30%
      pain relief) and PGIC very much improved (equivalent to at least 50% pain
      relief).For secondary efficacy outcomes, one study reported maximum and mean pain
      intensity and pain relief, and reported statistically significant improvements
      versus placebo for all outcomes with 20 mg daily doses of methadone, but not with
      10 mg daily doses. The second study reported differences in pain reduction
      between methadone (n = 26) and morphine (n = 38) and found morphine to be
      statistically superior. The third study reported the number of responders
      (variously defined) for several pain and functional outcomes and found methadone
      to be statistically superior to placebo for the outcomes of categorical pain
      intensity and evoked pain. In the two studies that reported data, 0/29
      participants withdrew due to lack of efficacy, whereas 4/29 participants withdrew
      due to adverse events while taking methadone versus 3/29 while taking placebo.One
      study reported incidences for several individual adverse events, but found a
      statistically significant increased incidence for methadone over placebo for only
      one event, dizziness. The other studies did not report data in a manner that
      enabled us to analyze adverse events. There were no serious adverse events or
      deaths reported.We assessed the quality of the evidence as very low for all
      efficacy and safety outcomes using GRADE, primarily because of the heterogeneity
      of study designs and populations, short durations, cross-over methodology, and
      few participants and events. AUTHORS' CONCLUSIONS: The three studies provide very
      limited, very low quality evidence of the efficacy and safety of methadone for
      chronic neuropathic pain, and there were too few data for pooled analysis of
      efficacy or harm, or to have confidence in the results of the individual studies.
      No conclusions can be made regarding differences in efficacy or safety between
      methadone and placebo, other opioids, or other treatments.

PMID- 28514510
TI  - Injury to the infrapatellar branch of the saphenous nerve during tendon graft
      harvesting for knee ligament reconstruction: An ultrasound simulation study.
AB  - The clinical anatomy of the infrapatellar branch of the saphenous nerve (IPBSN)
      is of particular importance during operations in the area of the knee, especially
      when material for anterior cruciate ligament reconstruction is harvested. The
      nerve can easily be injured during the harvesting procedure, leading to
      postoperative complications that reduce quality of life. Three different skin
      incisions are commonly used during hamstring tendon harvesting: horizontal,
      vertical, and oblique. The aim of this ultrasound simulation study was to assess
      the risk of IPBSN injury associated with the type of skin incision and the point
      of-emergence of the IPBSN relative to the sartorius muscle. Thirty healthy
      volunteers (60 lower limbs) were recruited for identification of the IPBSN. When
      it was found, using a high-frequency ultrasound probe, three different 3 cm skin
      incisions over the pes anserinus were simulated. Vertical, horizontal, or oblique
      lines simulating incisions were marked over the pes anserinus and ultrasound was
      used to visualize the structures that could be injured during the marked
      incisions. The IPBSN was visualized in 58 lower limbs (96.7%). The results of the
      simulation study indicated that the vertical incision should be avoided during
      hamstring tendon harvesting, as it is associated with a significantly higher risk
      of injury (25.9%) to the IPBSN than the horizontal (3.5%) or oblique (8.6%)
      incisions. We recommend that a preoperative ultrasound assessment of IPBSN
      anatomy be performed to minimize the risk of iatrogenic injury to the nerve and
      associated complications. Clin. Anat. 30:868-872, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28514509
TI  - The dimensions of the tarsal sinus and canal in different foot positions and its
      clinical implications.
AB  - This study presents a reference for the dimensions of the tarsal sinus and canal
      in healthy adults in different foot positions to facilitate understanding of the
      kinematics of the subtalar joint, the effect of an implant, and other clinical
      issues. In a 3D CT stress test on 20 subjects, the right foot was forced into a
      neutral and eight different extreme foot positions while CT scans were obtained.
      The bones were segmented in the neutral foot position. The kinematics of the
      bones in the extreme positions were determined relative to the neutral position.
      The dimensions of the tarsal sinus and canal were calculated by determining the
      radii of the maximal inscribed spheres at 20 equidistant locations along an axis
      in 3D surface models of the tali and calcanei in each foot position. The radii
      were small on the medial side and increased laterally. Medial from the middle,
      the radii were small and not significantly different among the various foot
      positions. At the lateral side, the dimensions were affected mainly by eversion
      or inversion and less by dorsiflexion or plantarflexion. The pattern was
      reproducible among subjects, but there were between-subject differences. The
      dimensions are mostly determined by rotation in the frontal plane. A pivot point
      was found medial from the middle. These data serve as a reference and model for
      predicting the effect of sinus implants and understanding such clinical problems
      as sinus tarsi syndrome. Between-subjects differences have to be taken into
      account. Clin. Anat. 30:1049-1057, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28514511
TI  - Experiences of xerostomia after radiotherapy in patients with head and neck
      cancer: A qualitative study.
AB  - AIMS AND OBJECTIVES: To describe the experiences of radiation-induced xerostomia
      in patients with head and neck cancer. BACKGROUND: Xerostomia is the most
      commonly occurring complication during and following radiotherapy. It can persist
      for several months or years and can have a significant impact on patients'
      quality of life. DESIGN: This was a qualitative descriptive study. METHODS: Semi
      structured interviews were conducted with a sample of 20 participants. Inductive
      content analysis was used to analyse the qualitative data. RESULTS: Analysis of
      the manifest content identified five categories: communication problems, physical
      problems, psychosocial problems, treatment problems and relief strategies. The
      latent content was formulated into a theme: due to lack of information from
      professionals, the patients had to find their own solutions for their problems.
      CONCLUSIONS: Xerostomia is not only a biophysical symptom but also has a profound
      effect on the emotional, intellectual and sociocultural dimensions of life. The
      majority of patients continued to suffer from xerostomia and its associated
      symptoms after radiotherapy, in part, because of a lack of professional support,
      including the inability of nurses to provide oral health care. RELEVANCE TO
      CLINICAL PRACTICE: Nurses need to be knowledgeable about the effects of
      radiotherapy on oral mucosa and about appropriate interventions. The healthcare
      system requires a symptom management platform for radiation-induced
      complications, to help patients, their families and healthcare professionals
      obtain information about self-care, treatments and relief strategies.

PMID- 28514512
TI  - Prevalence of the aberrant right subclavian artery reported in a published
      systematic review of cadaveric studies: The impact of an outlier.
AB  - The aberrant or anomalous right subclavian artery (ARSA), which arises directly
      from the aortic arch and crosses to the right side usually behind the esophagus,
      is a rare but clinically important anatomical variant. A published systematic
      review (SR) of 15 cadaveric studies on ARSA reported that prevalence ranged from
      0.2% to 13.3% of the general population; the total unweighted prevalence of ARSA
      was 325 cases in 13,208 bodies or 2.46%. The present review, however, found that
      the 13.3% figure was for 133 cases from a larger case series without a
      denominator. Three other studies either had an imprecise denominator or were
      limited to congenital conditions associated with ARSA. After exclusions and
      modifications, ARSA prevalence for the remaining 11 studies in the SR ranged from
      0.19%, with a 95% confidence interval (CI) of 0.00-1.08%, to 2.52% (CI= 0.69
      6.32%). The unweighted prevalence for all 11 studies combined was 1.23%, and the
      pooled prevalence estimate from a meta-analysis was 1.30% (CI = 0.86-1.82%). In
      conclusion, overall findings from SRs on the prevalence of rare anatomical
      variants such as ARSA may be affected by outliers. Clin. Anat. 30:1024-1028,
      2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28514513
TI  - Comprehensive database of Manufactured Gas Plant tars. Part C. Heterocyclic and
      hydroxylated polycyclic aromatic hydrocarbons.
AB  - RATIONALE: Coal tars are a mixture of organic and inorganic compounds that were
      by-products from the manufactured gas and coke making industries. The tar
      compositions varied depending on many factors such as the temperature of
      production and the type of retort used. For this reason a comprehensive database
      of the compounds found in different tar types is of value to understand both how
      their compositions differ and what potential chemical hazards are present. This
      study focuses on the heterocyclic and hydroxylated compounds present in a
      database produced from 16 different tars from five different production
      processes. METHODS: Samples of coal tar were extracted using accelerated solvent
      extraction (ASE) and derivatized post-extraction using N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane
      (TMCS). The derivatized samples were analysed using two-dimensional gas
      chromatography combined with time-of-flight mass spectrometry (GCxGC/TOFMS).
      RESULTS: A total of 865 heterocyclic compounds and 359 hydroxylated polycyclic
      aromatic hydrocarbons (PAHs) were detected in 16 tar samples produced by five
      different processes. The contents of both heterocyclic and hydroxylated PAHs
      varied greatly with the production process used, with the heterocyclic compounds
      giving information about the feedstock used. Of the 359 hydroxylated PAHs
      detected the majority would not have been be detected without the use of
      derivatization. CONCLUSIONS: Coal tars produced using different production
      processes and feedstocks yielded tars with significantly different heterocyclic
      and hydroxylated contents. The concentrations of the individual heterocyclic
      compounds varied greatly even within the different production processes and
      provided information about the feedstock used to produce the tars. The
      hydroxylated PAH content of the samples provided important analytical information
      that would otherwise not have been obtained without the use of derivatization and
      GCxGC/TOFMS.

PMID- 28514514
TI  - Alternation between short- and long photoperiod reveals hypothalamic gene
      regulation linked to seasonal body weight changes in Djungarian hamsters
      (Phodopus sungorus).
AB  - Djungarian hamsters are able to reduce their body weight by more than 30% in
      anticipation of the winter season. This particular adaptation to extreme
      environmental conditions is primarily driven by a natural reduction in day length
      and conserved under laboratory conditions. We used this animal model to
      investigate hypothalamic gene expression linked to body weight regulation behind
      this physiological phenomenon. After an initial collective short photoperiod (SP)
      adaptation for 14 weeks from a preceding long photoperiod (LP), hamsters were re
      exposed to LP for either 6 or 14 weeks, followed by a second re-exposure to SP
      for 8 weeks. Our data showed that re-exposure to LP led to an increase in body
      weight. In the hypothalamus Dio2, Vimentin, Crbp1 and Grp50 expression increased,
      whereas expression of Dio3, Mct8 and Srif decreased. The changes in body weight
      and gene expression were reversible in most hamsters after a further re-exposure
      to SP following 6 or 14 weeks in LP. Interestingly, after 14 weeks in LP, body
      weight loss was pronounced in six hamsters re-exposed to SP, but five hamsters
      did not respond. In nonresponding hamsters, a different gene expression pattern
      was manifested, with the exception of Dio2, which was reduced not only in SP re
      exposed hamsters, but also in hamsters maintained in LP. Taken together, these
      data suggest that body weight regulation appears to be tightly linked to a co
      ordinated regulation of several genes in the hypothalamus, including those
      involved in thyroid hormone metabolism.

PMID- 28514515
TI  - Detailed anatomy of the abducens nerve in the lateral rectus muscle.
AB  - The aims of this study were to elucidate the detailed anatomy of the abducens
      nerve in the lateral rectus muscle (LRM) and the intramuscular innervation
      pattern using Sihler staining. In this cohort study, 32 eyes of 16 cadavers were
      assessed. Dissection was performed from the LRM origin to its insertion. The
      following distances were measured: from LRM insertion to the bifurcation point of
      the abducens nerve, from LRM insertion to the entry site of the superior branch
      or inferior branch, from the upper border of the LRM to the entry site of the
      superior branch, from the lower border of LRM to the entry site of inferior
      branch, and the widths of the main trunk and superior and inferior branches. The
      single trunk of the abducens nerve divided into two branches 37 mm from insertion
      of the LRM, and 22 of 32 (68.8%) orbits showed only two superior and inferior
      branches with no subdivision. The superior branch entered the LRM more anteriorly
      (P = 0.037) and the superior branch was thinner than the inferior branch (P =
      0.040). The most distally located intramuscular nerve ending was observed at 52.9
      +/- 3.5% of the length of each muscle. Non-overlap between the superior and
      inferior intramuscular arborization of the nerve was detected in 27 of 32 cases
      (84.4%). Five cases (15.6%) showed definite overlap of the superior and inferior
      zones. This study revealed the detailed anatomy of the abducens nerve in the LRM
      and provides helpful information to understand abducens nerve palsy. Clin. Anat.
      30:873-877, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28514516
TI  - Which factors most influence referral for restorative dental treatment under
      sedation and general anaesthesia in children with complex disabilities: caries
      severity, child functioning, or dental service organisation?
AB  - BACKGROUND: The UN Convention on the Rights of the Child gives all children right
      to the highest standard of services for treatment and rehabilitation. For
      children with disabilities, sedation and general anaesthesia (GA) are often
      indicated for dental treatment; however, accessibility to this varies. The
      International Classification of Functioning, Disability and Health - Child and
      Youth version (ICF-CY) enables a biopsychosocial description of children
      undergoing dental treatment. AIM: To investigate conscious sedation and GA in
      children with complex disabilities and manifest caries and analyse how caries,
      child functioning, and dental service organisation relate to dental GA (DGA),
      comparing Argentina, France, and Sweden using the ICF-CY. DESIGN: Quantitative,
      cross-sectional; data collected through structured interviews, observation, and
      dental records. RESULTS: Sedation and DGA were common. Children with limitations
      in interpersonal interactions and relationships were more likely to have had DGA
      (OR: 5.3, P = 0.015). Level of caries experience was strongly correlated with
      experience of DGA. There were significant differences between countries regarding
      caries prevalence, sedation, DGA, and functional and environmental factors.
      CONCLUSIONS: Although caries experience and child functioning are important,
      dental health service organisation had the most impact on the incidence of DGA,
      and for the use of conscious sedation, for children with complex disabilities.

PMID- 28514517
TI  - Early childhood caries and psychological perceptions on child's oral health
      increase the feeling of guilt in parents: an epidemiological survey.
AB  - AIM: To assess whether parents feel guilty for their children's oral problems,
      associating this feeling with socio-economic, demographic, and psychological
      factors. DESIGN: We included 1313 parent-and-child pairs in this study. The
      children were 2-4 years old. Parents answered questionnaires on socio-economic
      and demographic data, and on psychological variables. Sixteen trained dentists
      (kappa > 0.8) examined the children for oral hygiene (the presence and absence of
      plaque), early childhood caries (ECC; no caries, low and high severity),
      malocclusion (the presence and absence), and traumatic dental injuries (TDI; the
      presence and absence). We analysed the data with a hierarchical regression.
      RESULTS: Twenty-four percentage of parents reported feeling guilty for the oral
      problems in their children; 26.3% of the children presented with caries, 39.8%
      malocclusion, 22.9% TDI. Of the parents who felt guilty, 54% thought that their
      children had problems in their teeth, and most of them (82%) thought that the
      problem could have been avoided. The feeling of guilt in parents was
      significantly associated with ECC and the psychological variables: the thought
      that the child had problems in his/her teeth and the thought that the problem
      could have been avoided. CONCLUSION: Parents feel more guilty with increased
      caries severity in their children, and the likelihood of feeling guilty increases
      when parents believe that their child has an oral problem or that this problem
      could have been avoided.

PMID- 28514518
TI  - A Retrosynthesis Approach for Biocatalysis in Organic Synthesis.
AB  - For the planning of an organic synthesis route, the disconnection approach guided
      by retrosynthetic analysis of possible intermediates and the chemical reactions
      involved, back to ready available starting materials, is well established. In
      contrast, such concepts just get developed for biocatalytic routes. In this
      Review we highlight functional group interconversions catalyzed by enzymes. The
      article is organized rather by chemical bonds formed-exemplified for C-N, C-O-
      and C-C-bonds-and not by enzyme classes, covering a broad range of reactions to
      incorporate the desired functionality in the target molecule. Furthermore, the
      successful use of biocatalysts, also in combination with chemical steps, is
      exemplified for the synthesis of various drugs and advanced pharmaceutical
      intermediates such as Crispine A, Sitagliptin and Atorvastatin. This Review also
      provides some basic guidelines to choose the most appropriate enzyme for a
      targeted reaction keeping in mind aspects like commercial availability, cofactor
      requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant
      microorganisms aiming to assist organic chemists in the use of enzymes for
      synthetic applications.

PMID- 28514520
TI  - Patient involvement in research - participants or collaborators?

PMID- 28514519
TI  - Patient involvement vs. patient participation in qualitative research in the
      development of PROMs.

PMID- 28514521
TI  - Combining frozen-density embedding with the conductor-like screening model using
      Lagrangian techniques for response properties.
AB  - We present the explicit derivation of an approach to the multiscale description
      of molecules in complex environments that combines frozen-density embedding (FDE)
      with continuum solvation models, in particular the conductor-like screening model
      (COSMO). FDE provides an explicit atomistic description of molecule-environment
      interactions at reduced computational cost, while the outer continuum layer
      accounts for the effect of long-range isotropic electrostatic interactions. Our
      treatment is based on a variational Lagrangian framework, enabling rigorous
      derivations of ground- and excited-state response properties. As an example of
      the flexibility of the theoretical framework, we derive and discuss FDE + COSMO
      analytical molecular gradients for excited states within the Tamm-Dancoff
      approximation (TDA) and for ground states within second-order Moller-Plesset
      perturbation theory (MP2) and a second-order approximate coupled cluster with
      singles and doubles (CC2). It is shown how this method can be used to describe
      vertical electronic excitation (VEE) energies and Stokes shifts for uracil in
      water and carbostyril in dimethyl sulfoxide (DMSO), respectively. In addition,
      VEEs for some simplified protein models are computed, illustrating the
      performance of this method when applied to larger systems. The interaction terms
      between the FDE subsystem densities and the continuum can influence excitation
      energies up to 0.3 eV and, thus, cannot be neglected for general applications. We
      find that the net influence of the continuum in presence of the first FDE shell
      on the excitation energy amounts to about 0.05 eV for the cases investigated. The
      present work is an important step toward rigorously derived ab initio multilayer
      and multiscale modeling approaches. (c) 2017 Wiley Periodicals, Inc.

PMID- 28514522
TI  - Use of Reversible Contraceptive Methods Among U.S. Women with Physical or Sensory
      Disabilities.
AB  - CONTEXT: Women with disabilities experience a higher rate of adverse pregnancy
      outcomes than women without disabilities. Preventing or delaying pregnancy when
      that is the best choice for a woman is a critical strategy to reducing pregnancy
      related disparities, yet little is known about current contraceptive use among
      women with disabilities. METHODS: A cohort of 545 reproductive-age women with
      physical disabilities (i.e., difficulty walking, climbing, dressing or bathing)
      or sensory disabilities (i.e., difficulty with vision or hearing) was identified
      from among participants in the 2011-2013 National Survey of Family Growth. Those
      at risk for unplanned pregnancy were categorized by whether they were using
      highly effective reversible contraceptive methods (IUD, implant), moderately
      effective ones (pill, patch, ring, injectable), less effective ones (condoms,
      withdrawal, spermicides, diaphragm, natural family planning) or no method.
      Multinomial regression was conducted to examine the association between
      disability and type of contraceptive used. RESULTS: Some 39% of women with
      disabilities were at risk of unplanned pregnancy, and 27% of those at risk were
      not using contraceptives. The presence of disability was associated with
      decreased odds of using highly effective methods or moderately effective methods,
      rather than less effective ones (odds ratio, 0.6 for each), but had no
      association with using no method. CONCLUSION: There is a significant need to
      reduce contraceptive disparities related to physical or sensory disabilities.
      Future research should explore the extent to which contraceptive use differs by
      type and severity of disability, as well as identify contextual factors that
      contribute to any identified differences.

PMID- 28514523
TI  - The views of older people and health professionals about dignity in acute
      hospital care.
AB  - AIMS AND OBJECTIVES: To report the findings from interviews conducted as part of
      a wider study on interventions to support dignified care in older people in acute
      hospital care. The data in this study present the interview data. BACKGROUND:
      Dignity is a complex concept. Despite a plethora of recommendations on how to
      achieve dignified care, it remains unclear how to attain this in practice and
      what the priorities of patients and staff are in relation to dignity. DESIGN: A
      purposive sample of older patients and staff took part in semi-structured
      interviews and gave their insight on the meaning of dignity and examples of what
      sustains and breaches a patient's dignity in acute hospital care. METHOD:
      Thirteen patients and 38 healthcare professionals in a single metropolitan
      hospital in the UK interviewed. Interviews were transcribed verbatim and
      underwent a thematic analysis. RESULTS: The meaning of dignity was broadly agreed
      on by patients and staff. Three broad themes were identified: the meaning of
      dignity, staffing level and its impact on dignity, and organisational culture and
      dignity. Registered staff of all healthcare discipline and student nurses report
      very little training on dignity or care of the older person. CONCLUSION: There
      remain inconsistencies in the application of dignified care. Staff behaviour, a
      lack of training and the organisational processes continue to result in breaches
      to dignity of older people. Clinical nurses have a major role in ensuring
      dignified care for older people in hospital. RELEVANCE TO CLINICAL PRACTICE:
      There needs to be systematic dignity-related training with regular refreshers.
      This education coupled with measures to change the cultural attitudes in an
      organisation towards older peoples' care should result in long-term improvements
      in the level of dignified care. Hospital managers have an important role in
      changing system to ensure that staff deliver the levels of care they aspire to.

PMID- 28514524
TI  - Transition from hospital to home: Parents' perception of their preparation and
      readiness for discharge with their preterm infant.
AB  - AIMS AND OBJECTIVES: To explore the experiences of parents with babies born
      between 28-32 weeks' gestation during transition through the neonatal intensive
      care unit and discharge to home. BACKGROUND: Following birth of a preterm baby,
      parents undergo a momentous journey through the neonatal intensive care unit
      prior to their arrival home. The complexity of the journey varies on the degree
      of prematurity and problems faced by each baby. The neonatal intensive care unit
      environment has many stressors and facilitating education to assist parents to
      feel ready for discharge can be challenging for all health professionals. DESIGN:
      Qualitative descriptive design. METHODS: The project included two phases, pre-
      and postdischarge, to capture the experiences of 20 couples (40 parents), whilst
      their baby was a neonatal intensive care unit inpatient and then after discharge.
      Face-to-face interviews, an online survey and telephone interviews were employed
      to gather parent's experiences. Constant comparative analysis was used to
      identify commonalities between experiences. Recruitment and data collection
      occurred from October 2014-February 2015. RESULTS/FINDINGS: Overlapping themes
      from both phases revealed three overarching concepts: effective parent staff
      communication; feeling informed and involved; and being prepared to go home.
      CONCLUSION: Our findings can be used to develop strategies to improve the
      neonatal intensive care unit stay and discharge experience for parents. Proposed
      strategies would be to improve information transfer, promote parental contact
      with the multidisciplinary team, encourage input from fathers to identify their
      needs and facilitate parental involvement according to individual needs within
      families. RELEVANCE TO CLINICAL PRACTICE: Providing information to parents during
      their time in hospital, in a consistent and timely manner is an essential
      component of their preparation when transitioning to home.

PMID- 28514525
TI  - Responsiveness of the Arabic version of the ECOHIS to dental rehabilitation under
      general anaesthesia.
AB  - BACKGROUND: The Arabic version of the Early Childhood Oral Health Impact Scale (A
      ECOHIS) has been validated, but its ability to detect change was not tested. AIM:
      To evaluate the responsiveness of the A-ECOHIS to dental rehabilitation under
      general anaesthesia (DRGA). DESIGN: A consecutive sample of 131 parents of
      children aged 6 years or younger, scheduled for DRGA were recruited from three
      public hospitals. The parents completed the A-ECOHIS before and 4 weeks following
      DRGA. The responsiveness of the A-ECOHIS was assessed by evaluating changes in
      scores before and after DRGA, and by measuring the change in scores in relation
      to the global question. RESULTS: The A-ECOHIS scores were higher among parents
      who reported poor oral health on the global question than those reporting better
      oral health (P = 0.001). There was a significant reduction in the scores at
      follow-up (P < 0.001). The effect size was 1.5 for the total scale, and 1.3 and
      1.6 for the child and family impacts, respectively. After DRGA, the child and
      family impact section scores decreased by 78.6% and 77.9%, respectively. The
      majority of parents reported improvement in children's overall oral health
      related quality of life post-operatively (94%). CONCLUSION: The A-ECOHIS was
      responsive to DRGA.

PMID- 28514526
TI  - Direct medial approach in surgical fixation of fractures in the posterior aspect
      of the medial malleolus.
AB  - Fractures in the posterior aspect of the medial malleolus form an important
      subset of ankle fractures and the indications for fixation include involvement of
      > 25% of the articular surface or an articular step off by > 2 mm. Several
      approaches have been described but there has been no recent study on the direct
      medial approach. Five fresh frozen cadaveric ankles were dissected using the
      direct medial approach. A longitudinal incision of 10 cm was centered directly
      over the medial malleolus and deepened straight down to the bone. The periosteum
      was identified over the distal tibia and careful subperiosteal dissection yielded
      access to the posterior aspect of the medial malleolus. We investigated the
      relationship of the neurovascular bundle to the incision by measuring the
      distance from the center of the medial malleolus to the closest aspect of the
      bundle. The mean distance from the center of the medial malleolus to the
      neurovascular bundle was only 2.64 cm (95% CI: 2.06 to 3.22 cm). We found that
      the neurovascular bundle could be avoided if a periosteal sheath was developed
      during the dissection and elevated off the posterior aspect of the medial
      malleolus. The direct medial approach can be performed safely by creating a
      periosteal sheath through subperiosteal dissection, and the distance of the
      neurovascular bundle from the incision allows for a good margin of safety during
      surgery. This approach can be extended proximally and distally and the medial
      malleolus can be fixed concurrently. Clin. Anat. 31:605-607, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28514528
TI  - Overcoming the Instability of Nanoparticle-Based Catalyst Films in Alkaline
      Electrolyzers by using Self-Assembling and Self-Healing Films.
AB  - Engineering stable electrodes using highly active catalyst nanopowders for
      electrochemical water splitting remains a challenge. We report an innovative and
      general approach for attaining highly stable catalyst films with self-healing
      capability based on the in situ self-assembly of catalyst particles during
      electrolysis. The catalyst particles are added to the electrolyte forming a
      suspension that is pumped through the electrolyzer. Particles with negatively
      charged surfaces stick onto the anode, while particles with positively charged
      surfaces stick to the cathode. The self-assembled catalyst films have self
      healing properties as long as sufficient catalyst particles are present in the
      electrolyte. The proof-of-concept was demonstrated in a non-zero gap alkaline
      electrolyzer using NiFe-LDH and Nix B catalyst nanopowders for anode and cathode,
      respectively. Steady cell voltages were maintained for at least three weeks
      during continuous electrolysis at 50-100 mA cm-2 .

PMID- 28514529
TI  - The effect of repeated freeze-thaw cycles on human muscle tissue visualized by
      postmortem computed tomography (PMCT).
AB  - The aim of this study was to determine whether effects of repetitive freeze-thaw
      cycles, with various thawing temperatures, on human muscle tissue can be
      quantified using postmortem computed tomography (PMCT) technology. An additional
      objective was to determine the preferred thawing temperature for muscle tissue in
      this study. Human cadaver upper extremities were divided into two different
      thawing temperature groups and underwent a series of four freeze-thaw cycles in
      total. Axial CT scans were performed after each cycle. CT attenuation (in
      Hounsfield units, HU) was measured in four muscles of the upper extremities. HU
      values changed significantly with the introduction of each subsequent freeze-thaw
      cycle. Moreover, the changes in HU values were different for each thawing group.
      There was a significant increase of HU values in both groups between t0 and t1 .
      Unfrozen tissue showed large variation of HU values in all samples. It was
      possible to distinguish between samples thawed at different thawing temperatures
      based on their respective HU values. It is advisable to keep the number of freeze
      thaw cycles to just one, if the human cadaveric tissue is to be used for
      educational purposes. The preferred thawing temperature in this study is 2
      degrees C. Clin. Anat. 30:799-804, 2017. (c) 2017Wiley Periodicals, Inc.

PMID- 28514527
TI  - Efficacy and Safety of Injectable Robenacoxib for the Treatment of Pain
      Associated With Soft Tissue Surgery in Dogs.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used routinely to
      control pain and inflammation after surgery in dogs. Robenacoxib is a
      cyclooxygenase-2 selective NSAID. HYPOTHESIS/OBJECTIVE: Assess the clinical
      efficacy and safety of an injectable formulation of robenacoxib in dogs
      undergoing surgery. ANIMALS: Three hundred and seventeen client-owned dogs (N =
      159 robenacoxib or N = 158 placebo). METHODS: In this prospective, multicenter,
      randomized, masked, placebo-controlled, parallel-group study, dogs received a SC
      injection of either robenacoxib, at a target dose of 2.0 mg/kg, or placebo once
      prior to surgery and for 2 additional days postoperatively. Pain assessments were
      performed using the short form of the Glasgow Composite Measure Pain Scale (CMPS
      SF). The primary efficacy variable was treatment success/failure, with failure
      defined as the need for rescue therapy to control pain or withdrawal of the dog
      from the study due to an adverse event. RESULTS: Significantly (P = .006) more
      dogs administered robenacoxib were considered treatment successes (108 of 151,
      73.7%) compared to dogs given placebo (85 of 152, 58.1%). Total pain scores (P <
      .01), pain at the surgery sites (response to touch, P < .01), and
      posture/activity (P < .05) were significantly improved at 3, 5, and 8 hours
      postextubation in dogs receiving robenacoxib versus placebo. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Robenacoxib administered by SC injection prior to surgery
      and for 2 additional days postoperatively was effective and well tolerated in the
      control of postoperative pain and inflammation associated with soft tissue
      surgery in dogs.

PMID- 28514530
TI  - Curious, thoughtful and affirmative-Young children's meanings of participation in
      healthcare situations when using an interactive communication tool.
AB  - AIMS AND OBJECTIVES: To describe young children's demonstrated participation in
      healthcare situations while using an interactive communication tool. BACKGROUND:
      Participation is a multidimensional concept influenced by situational and
      contextual issues. In child participation, verbal and nonverbal communicative
      expressions are of interest, as both demonstrate the child's perspective.
      Children have a right to participate in all situations that matter to them, for
      instance healthcare situations. Children, understood as social actors, express a
      wish and a need to participate in these situations to get information and to
      enable preparation. DESIGN/METHOD: In a pilot study, video observations were used
      to capture the children's use of the interactive communication tool in healthcare
      situations. A hermeneutic analysis was conducted to achieve a deeper
      understanding of the children's demonstrated cues of participation. RESULTS: The
      expressed cues of participation were understood as having either a curious,
      thoughtful or affirmative meaning of participation and there was a continuous
      movement between them. Curious cues were expressed when introducing or
      reintroducing the tool in the situation and demonstrated a wish to get knowledge
      of the things shown on the screen or to perform the virtual tasks. Thoughtful
      cues slowed down the progression of the situation when the children needed time
      to think or adapt to the virtual procedures. Affirmative cues were self-rewarding
      and demonstrated at successful task performance. CONCLUSION: An interactive
      communication tool used in healthcare situations can promote young children's
      understanding and facilitate their situated participation, which potentially
      reduces feelings of distress or anxiety. This innovative use of interactive
      technology within paediatric health care provides new ways of revealing the
      child's perspective in the situation. RELEVANCE TO CLINICAL PRACTICE: Interactive
      technology improves understanding and participation of children in healthcare
      situations, which impact them positively, both in the present and for the future.
      A communication tool enhances professionals' opportunities to adopt a child
      centred approach by responding sensitively to the children's expressions.

PMID- 28514531
TI  - Safety and service: Reframing the purpose of nursing to decision-makers.

PMID- 28514533
TI  - Antecedents and consequences of workplace violence against nurses: A qualitative
      study.
AB  - AIMS AND OBJECTIVES: To explore Iranian nurses' perceptions of and experiences
      with the antecedents and consequences of workplace violence perpetrated by
      patients, patients' relatives, colleagues and superiors. BACKGROUND: Workplace
      violence against nurses is a common problem worldwide, including in Iran.
      Although many studies have reviewed the antecedents and consequences of workplace
      violence, limited information is available on this topic. An understanding of the
      predisposing factors for violence and the consequences of violence is essential
      to developing programs to prevent and manage workplace violence. DESIGN:
      Qualitative descriptive design. METHODS: In this qualitative study, 22
      unstructured, in-depth interviews were conducted with registered nurses who had
      experienced workplace violence and who were selecting using purposive sampling in
      nine hospitals. Inductive content analysis was used to analyse the data. RESULTS:
      Five categories emerged as predisposing factors: unmet expectations of
      patients/relatives, inefficient organisational management, inappropriate
      professional communication, factors related to nurses and factors related to
      patients, patients' relatives and colleagues. Individual, familial and
      professional consequences were identified as outcomes of workplace violence
      against nurses. CONCLUSIONS: Workplace violence by patients/their relatives and
      colleagues/superiors is affected by various complicated factors at the individual
      and organisational levels. In addition to negatively affecting nurses' individual
      and family lives, workplace violence may lead to a lower quality of patient care
      and negative attitudes towards the nursing profession. RELEVANCE TO CLINICAL
      PRACTICE: Identifying factors, which lead to workplace violence, could help
      facilitate documenting and reporting such incidents as well as developing the
      necessary interventions to reduce them. Furthermore, native instruments must be
      developed to predict and monitor violence.

PMID- 28514534
TI  - Anticipatory vigilance: A grounded theory study of minimising risk within the
      perioperative setting.
AB  - AIMS AND OBJECTIVES: To explore and explain how nurses minimise risk in the
      perioperative setting. BACKGROUND: Perioperative nurses care for patients who are
      having surgery or other invasive explorative procedures. Perioperative care is
      increasingly focused on how to improve patient safety. Safety and risk management
      is a global priority for health services in reducing risk. Many studies have
      explored safety within the healthcare settings. However, little is known about
      how nurses minimise risk in the perioperative setting. DESIGN: Classic grounded
      theory. METHODS: Ethical approval was granted for all aspects of the study.
      Thirty-seven nurses working in 11 different perioperative settings in Ireland
      were interviewed and 33 hr of nonparticipant observation was undertaken.
      Concurrent data collection and analysis was undertaken using theoretical
      sampling. Constant comparative method, coding and memoing and were used to
      analyse the data. RESULTS: Participants' main concern was how to minimise risk.
      Participants resolved this through engaging in anticipatory vigilance (core
      category). This strategy consisted of orchestrating, routinising and momentary
      adapting. CONCLUSION: Understanding the strategies of anticipatory vigilance
      extends and provides an in-depth explanation of how nurses' behaviour ensures
      that risk is minimised in a complex high-risk perioperative setting. This is the
      first theory situated in the perioperative area for nurses. RELEVANCE TO CLINICAL
      PRACTICE: This theory provides a guide and understanding for nurses working in
      the perioperative setting on how to minimise risk. It makes perioperative nursing
      visible enabling positive patient outcomes. This research suggests the need for
      training and education in maintaining safety and minimising risk in the
      perioperative setting.

PMID- 28514535
TI  - Analysis of mortality in individuals over 60 years of age in inner Mongolia
      between 2008 and 2012.
AB  - Our study was designed to determine the cause of death in people over 60 years of
      age in Inner Mongolia. We performed quantitative analysis of mortality rate, with
      a special focus on the population characteristics in the Inner Mongolia region of
      China to provide a reference for future studies. Data were obtained from the
      Centers for Disease Control from six monitoring points of Death Registry System
      (DRS) in Inner Mongolia, covering the period 2008-2012 years. We calculated the
      crude mortality rate over five years, as well as the causes of death and
      potential-years of life lost (PYLL) by gender over the same time period. We also
      calculated the crude mortality across different age-specific groups, and analyzed
      cause of death across these groups. Between 2008 and 2012, the crude mortality
      rate of individuals in Inner Mongolia aged 60 years or older was 3366,73 /100
      000. The crude mortality rate was higher among males (4158,68/100 000) than among
      females (2633,22/100 000), resulting in a male-female mortality ratio of 1,58 and
      a total PYLL of 48 968 person-years for males and females combined. Diseases of
      the circulatory system were the greatest contributor to mortality (1978,50/100
      000) and PYLL (25 700 person-years).The frequency of deaths due to diseases of
      the circulatory and respiratory systems increased with age, while the proportion
      of neoplasms declined with age. The mortality of individuals in Inner Mongolia
      over 60 years of age is moderate compared with studies of other Chinese
      populations. Diseases of the circulatory system, neoplasms, and diseases of the
      respiratory system were the leading causes of death. We therefore recommend that
      healthy lifestyle choices be advocated among the elderly to reduce the incidence
      of chronic, non-communicable diseases.

PMID- 28514532
TI  - The Dickkopf1-cytoskeleton-associated protein 4 axis creates a novel signalling
      pathway and may represent a molecular target for cancer therapy.
AB  - : Dickkopf 1 (DKK1) is a secreted protein and antagonizes oncogenic Wnt
      signalling by binding to the Wnt co-receptor, low-density lipoprotein receptor
      related protein 6. DKK1 has also been suggested to regulate its own signalling,
      associated with tumour aggressiveness. However, the underlying mechanism by which
      DKK1 promotes cancer cell proliferation has remained to be clarified for a long
      time. The cytoskeleton-associated protein 4 (CKAP4), originally identified as an
      endoplasmic reticulum membrane protein, was recently found to act as a novel DKK1
      receptor. DKK1 stimulates cancer cell proliferation when CKAP4 is expressed on
      the cell surface membrane. Although there are no tyrosine residues in the
      intracellular region of CKAP4, CKAP4 forms a complex with PI3K upon the binding
      of DKK1, leading to the activation of Akt. Both DKK1 and CKAP4 are frequently
      expressed in pancreatic and lung tumours, and their simultaneous expression is
      negatively correlated with prognosis. Knockdown of CKAP4 in cancer cells and
      treatment of mice with the anti-CKAP4 antibody inhibit Akt activity in cancer
      cells and suppress xenograft tumour formation, suggesting that CKAP4 may
      represent a therapeutic target for cancers expressing both DKK1 and CKAP4. This
      review will provide details of the novel DKK1-CKAP4 signalling axis that promotes
      cancer proliferation and discuss the possibility of targeting this pathway in
      future cancer drug development. LINKED ARTICLES: This article is part of a themed
      section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the
      other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.

PMID- 28514536
TI  - [Life span, longevity and incidence of violence death in writers and poets].
AB  - The article provides information on the mean age of death (MAD) those
      professionally involved in literary work (22 028 men and women 4 651) assigned to
      one of three categories: novelists, poets and writers-poets. Women any of the
      investigated categories authentically lived longer than men (p<0,02). Analysis of
      dynamics of mean age of death (MAD), starting from the 15th century BC to the end
      of the 20th century, showed that this ratio gradually increased but uneven among
      fiction writers and novelists, poets of both sexes, however, remained unchanged
      at poets and poetesses have declined. Among men the very old (90+ years) were
      5,38 % and 3,01 % writers-poets, whereas among women - 12,35 and 8,96 %,
      respectively. Centenarians have surpassed 1,62 % of women novelists and 0,61 %
      poets, then among men - 0,31 % and 0,49 % of writers, novelists and poets,
      respectively. The frequency of violent deaths (homicide, suicide, accidents) is
      also varied and was highest among poets, novelists, poets have minimum-novelists
      occupied an intermediate position for these indicators. Histogram of MAD had 2
      peakes type, characteristic for heterogeneous populations, with a sample of
      "writers" heterogeneity was weakly expressed, however in a sample of "poets" was
      very noticeable. Suggests that MAD, longevity, as well as the frequency of
      violent deaths are related to processes associated with creativity.

PMID- 28514537
TI  - [Suppression of alternative telomere lengthening in cancer cells with reverse
      transcriptase inhibitors].
AB  - Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore
      maintains chromosomal stability in germline, and in the majority of cancer cells,
      during cell doubling. However, up to 30 % of human tumors of different types do
      not express telomerase, but instead use an alternative lengthening of telomeres
      (ALT). Here authors show that human tumor-derived ALT cell lines express a LINE-1
      (L1) retrotransposon, which suggests its participation in telomere maintenance,
      possibly by a "slippage" mechanism of telomeric DNA synthesis. Moreover,
      suppression of the L1 encoded reverse transcriptase activity using an antisense
      strategy, or treatment of the ALT cells with the reverse transcriptase inhibitor
      3'-azido-2',3'-dideoxythymidine (AZT), induces progressive telomere loss, arrest
      in G2-phase of the cell cycle, and, eventually, in cancer cell death. This
      finding suggests an exciting opportunity for the cure of up to 30 % of cancer
      cases.

PMID- 28514538
TI  - [Lamin B1 and lamin B2 in human skin in the process of aging].
AB  - The aim of this work was to study B type lamins in human skin at different ages.
      Lamins B1 and B2 were detected in sections of the skin by indirect
      immunohistochemistry. There were 62,3 % of dermal fibroblasts with positive
      staining for lamin B1 at the period from 20 to 40 weeks of gestation. From birth
      to 40 years, 41-42 % of fibroblasts containing lamin B1 were found in the dermis.
      In age interval from 41 to 85 years, 57-60 % of dermal fibroblasts had a positive
      staining for lamin B1. The number of fibroblasts containing lamin B2 was
      gradually decreased from 80,6 to 68,6 % from 20 weeks of gestation to 85 years
      old. Expression of lamin B1 in the nuclei of fibroblasts was reduced from birth
      to 40 years old. Content of lamin B2 in the nuclei of fibroblasts was almost
      constant from 20 weeks of gestation to 85 years old. Number of fibroblasts in
      dermis was diminished with age. The most significant decrease in the number of
      fibroblasts was observed from 20 weeks of gestation to 20 years old. Results
      allow to suggest the participation of lamin B1 in triggering age-dependent
      decrease in the number of fibroblasts in the dermis in humans.

PMID- 28514539
TI  - [The age changes of lymphoid organs structure: review of literature].
AB  - Numerous and often contradictory research results specify that the mechanism of
      increased susceptibility to diseases in old age has no satisfactory explanation
      so far. Together with it in literature almost completely there are no comparative
      data on features of surgery and injury influence on a structure and functions of
      lymphoid organs at patients of different age groups. However, lymph nodes are a
      marker of activity of inflammatory process in the region, on their changes it is
      possible to estimate precisely productivity of different medical actions, to
      predict development of many complications, and, thus, successfully to take
      actions for their prophylaxis. All this is especially important and actual
      because of constant increase in average age, in life expectancy of human
      population and strengthening of surgical activity at patients of advanced and old
      age.

PMID- 28514540
TI  - [Age-related changes in biogenic amine content and oxidative stress profile in
      the rat hypothalamus in hyperhomocysteinemia].
AB  - The article presents a detailed analysis of correlations between the content of a
      variety of biogenic amines in the hypothalamic structures responsible for the
      luteinizing hormone releasing hormone synthesis and secretion (the medial
      preoptic area and median eminence) and such independent factors as total L
      homocysteine plasma level elevation induced by L-methionine loading and aging.
      Both a nature and a pattern of changes in oxidative stress profile were
      evaluated. It was shown that ageing, when compared to hyperhomocysteinemia, is a
      determining factor influencing biogenic amine content in the studied hypothalamic
      structures. Unlike antioxidant defense system profile, considerable changes in
      macromolecule oxidative modification were not found, which evidences a balanced
      activity of pro- and antioxidant systems in the hypothalamus.

PMID- 28514541
TI  - [Age-related expression of calcium-binding proteins in autonomic ganglionic
      neurons].
AB  - Calbindin 28 kDa (CB), calretinin (CR) and parvalbumin (PB) are belonged to
      calcium-binding proteins which are widely distributed in the nervous system and
      selectively expressed in certain population of neurons. These proteins are
      expressed not only in the central nervous system, but also in the autonomic
      ganglia. CB and PB are found in the sympathetic ganglia of rodents, CB and CR are
      found in metasympathetic intramural ganglia. Their functions are poor understood
      but one can suggest their important role in regulation of the Ca2+ level in the
      cell. Salcium-binding proteins are also play an important role in the development
      of autonomic neurons. There is an increasing of the percentage of CB and CR in
      the metasympathetic intramural ganglia of small intestine in the early postnatal
      development, whereas in sympathetic ganglia the percentage of CB is decreased.
      Possibly, the functional meaning of such changes can be explained by the role of
      calcium currents in the development of neurons and the synaptic transmission.

PMID- 28514542
TI  - [Neurohumoral changes in rats of different aged groups on the background of
      injection of cryopreserved nucleated cells of cord blood].
AB  - The application of the cryopreserved preparation of UCB NCs was accompanied by an
      enhanced activity of all the neurohumoral regulation elements of heart rate,
      although the absolute indices in 18- and 24-month-old animals did not reach
      similar ones in younger age groups. Also we noted an increase of thyroid hormone
      content in blood serum of aged rats, the level of which decreased with age. In
      addition, there was shown that the introduction of UCB NCs during animal life
      cycle (every 6 months) allowed keeping a functional state of the autonomic
      nervous system at a "young" physiological level.

PMID- 28514543
TI  - [The changes in hormonal status of the cardiovascular and the thyroid systems in
      rats with 18-month type 2 diabetes mellitus].
AB  - Among the most common complications of type 2 diabetes mellitus (DM2) are
      disorders of the cardiovascular and the thyroid systems. The functions of these
      systems may be weakened with increasing age. However, the mechanisms of these
      disorders, including the role of alterations in the adenylyl cyclase signaling
      system (ACSS), are not fully elucidated. Objective was to study thyroid status
      and ACSS activity of the myocardium and the thyroid gland (TG) of rats with 8-
      and 18-month DM2 (DM-8 and DM-18) as compared to control animals of the same age
      (C-8 and C-18). In the myocardium of rats with DM2 an imbalance of beta
      adrenergic regulation of ACSS was detected, and these disturbances were amplified
      with increasing age. In the myocardium of rats of the C-18 group the disturbances
      of ACSS hormonal regulation were also identified, but they were less pronounced.
      In diabetic rats, the levels of free thyroxine and total triiodothyronine
      decreased, the level of thyroid stimulating hormone (TSH) increased, and the
      stimulatory effect of TSH on the ACSS in TG was attenuated, which indicates the
      hypothyroid state in long-term DM2. In the C-18 group, these changes were absent.
      Thus, in the myocardium and TG of rats with 18-month DM2 the hormonal regulation
      of ACSS was violated, which may be one of the causes of cardiovascular pathology
      and hypothyroid states in long-term DM2.

PMID- 28514544
TI  - [Geriatric aspects in oncocoloproctology (review)].
AB  - Severe comorbidity significantly limits the use of active surgical tactics in
      patients of older age groups suffering from colorectal cancer (CRC), leading to
      the abandonment of the necessary operations in 20 % of cases. The low use of
      radical surgical tactics are not always related to objective difficulties, but
      often can be due to the stereotypical approach to solving the question of the
      treatment of the elderly patient, which leads to unreasonable refusal of surgical
      intervention. Today is not defined by a single concept of surgical treatment of
      patients with colon cancer in elderly and senile age. There is no universally
      accepted system for determining the functional operability in this group of
      patients, not developed specific algorithms for their preoperative preparation
      and perioperative management. In this regard, the search for new approaches to
      surgical treatment of geriatric patients with CRC, allowing, on the one hand, to
      increase the percentage of completion radical surgery, and on the other, to
      reduce the number of postoperative complications in this numerous group of
      patients, is one of the priority tasks of Oncology.

PMID- 28514545
TI  - [Diagnostics of the changes arising in an oral cavity at oncological sick senior
      age groups (review)].
AB  - Article is devoted to the changes happening in an oral cavity and in oral liquid
      under the influence of preparations of the oncological diseases used for
      treatment. Considering that research of oral liquid belongs to one of noninvasive
      methods of diagnostics and can be used with success for definition and correction
      of conditions of the mucous membrane of an oral cavity at the patients of
      advanced and senile age passing polychemotherapeutic treatment, this type of
      research is the extremely perspective for a gerontostomatology.

PMID- 28514546
TI  - [Luzindol accelerates the aging of estrous function of female rats].
AB  - In this paper, we investigated the dynamics of aging of the estrous function of
      female rats kept in the conditions of standard vivarium lighting and receiving
      luzindol - the blocker of melatonin receptors. Every three months, daily, for two
      weeks, vaginal smears were taken from the animals and cytological examination of
      the vaginal contents was conducted. Despite different mechanisms of the
      development of melatonin system failure (a decreased production of melatonin and
      a blockade of melatonin receptors), the effects of the influence on the ovulatory
      function are similar. In case of the blockade of melatonin receptors, the
      appearance of premature signs of aging of the reproductive function in rats was
      observed. It was manifested by an increased duration of ovulatory cycle; a
      decrease in the number of regular cycles; the emergence of irregular cycles; a
      decrease in the number of short estrous cycles and an increase of long cycles;
      the early development of persistent estrus.

PMID- 28514547
TI  - [Evidence of feasibility etoricoxib therapy in osteoarthritis in elderly
      patients].
AB  - The article presents the results of a study of clinical efficacy in the treatment
      of etorikoxib pain in patients with osteoarthritis of the knee and hip joints in
      elderly patients. The study involved 296 patients with gonarthrosis and
      coxarthrosis. It is shown that etoricoxib effectively relieves pain, has an
      advantage over other NSAIDs speed and severity of the analgesic and anti
      inflammatory effect, positive impact on laboratory signs of inflammation,
      demonstrated good tolerability and a low incidence of side effects, does not
      require discontinuation of therapy.

PMID- 28514548
TI  - [The effect of vascular peptide bioregulator on the microcirculation in the brain
      cortex of old rats].
AB  - Using a TV device to study brain microcirculation, we found that after a course
      of vascular peptide bioregulator the density of microvascular network of pia
      matter of old rats (22-24 months) sensomotor cortex increased about 2,5-2,8 times
      compared to control old rates; and noradrenaline-induced constriction reactions
      and acetylcholine-induced dilative reactions of the pial arterioles increased
      significantly. This perfusion in the tissue of the cerebral cortex is not
      increased, but the degree of blood oxygen saturation in the microvasculature of
      this tissue region raised.

PMID- 28514550
TI  - [Screening tools for frailty in ambulatory care].
AB  - The article gives a brief description of the frailty syndrome and comprehensive
      geriatric assessment. We describe two classical models - a model of the phenotype
      and the index of the frailty. The basic questionnaires for frailty syndrome
      screening in outpatient practice, as well as research on the validation of these
      questionnaires are presented. The results of comparative studies of
      questionnaires for frailty screening are shown.

PMID- 28514549
TI  - [Digoxin in elderly patients: therapeutic drug monitoring to increase the
      efficiency of therapy (a review)].
AB  - The focus of this review is on cardiac and non-cardiac effects of digoxin, a drug
      used for treating the heart failure, and on link between these effects and the
      serum digoxin concentration (SDC) in different dosing regimens. Elderly patients
      are at the spotlight, as they are both at high risk and high potential benefit
      from digoxin therapy, explaining potential usefulness from SDC monitoring in this
      cohort of patients. The laboratory and clinical approaches used to prevent
      digitalis intoxication are reviewed, with regard to their fidelity, clinical
      value, and practical usefulness. The role of endogenous cardiotonic steroids,
      sharing structural and functional similarity to digoxin and affecting the
      diagnostic value of laboratory tests, is also discussed.

PMID- 28514551
TI  - [Kidney function at patients of advanced and senile age before and in 24, 48, 120
      hours after carrying out X-ray endovascular intervention].
AB  - Research of a functional condition of kidneys at patients of advanced and senile
      age before and in 24, 48, 120 hours after carrying out X-ray endovascular
      intervention. Patients of age groups are examined: 34-59 years (49,7+/-7,8) - 35
      people (group of control), 60-74 years (66,1+/-4,1) - 48 people and 75-82 years
      (78,8+/-4,2) - 22 people. Sonclusion: it is confirmed the fact that at patients
      of advanced and senile age dynamic control of a functional condition of kidneys
      after 1st, 3rd and 5th days and till 3 weeks after carrying out X-ray
      endovascular interventions is necessary.

PMID- 28514553
TI  - [Significance of insulin resistance in the pathogenesis of sarcopenia and chronic
      heart failure in elderly hypertensive patients].
AB  - To determine the pathogenic role of insulin resistance in the formation of
      involutive sarcopenia and chronic heart failure (CHF) were examined 88 elderly
      patients with arterial hypertension (AH) and 32 elderly patients without
      cardiovascular disease by methods of carbohydrate metabolism and the level of
      brain natriuretic peptide precursor evaluation, muscle mass and strength
      measuring, echocardiography, 6 minute walking test. It was found that in the
      group of hypertensive patients with low mass and muscle strength significantly
      increased indices of insulin resistance and more expressed signs of the left
      ventricle myocardial dysfunction and functional class of heart failure, probably
      as a result of disorders of energy homeostasis, resulting from the deterioration
      of glucose into the muscle cells of the heart and skeletal muscles.

PMID- 28514552
TI  - [Features of the periodontal pathology at patients with metabolic syndrome].
AB  - The purpose of this article is to familiarize readers on the relationship between
      metabolic syndrome and periodontitis, as well as common pathogenetic processes
      underlying these diseases. The data of modern researches, devoted to the
      correlation of lesions of periodontal and systemic diseases associated with
      metabolic syndrome. In the article analyzed also the data of the original study
      of the interaction of periodontitis and metabolic syndrome, which also used
      special methods of examination like Doppler ultrasound microcirculatory
      vasculature of the periodontal tissues and ultrasound densitometry. The possible
      methods of diagnostics of a condition of periodontal tissues in patients with
      metabolic syndrome are considered. Conclusions about the relationship of each
      component of metabolic syndrome with periodontitis are made.

PMID- 28514554
TI  - [Self-consciousness in elderly persons with cognitive impairment and vascular
      dementia].
AB  - Self-consciousness was compared in 17 elderly (aged 65-89 years old) persons with
      cognitive impairment without dementia and 17 patients with vascular dementia.
      Neurocognitive functions and mental health complaints were evaluated.
      Neuropsychological assessment included evaluation of higher psychological
      functions, such as attention, memory, conceptualization, gnosis (optic,
      acoustic), manual skill, speech. Older persons with cognitive impairment assessed
      their neurocognitive functions adequately. Patients with vascular dementia
      usually denied cognitive deficit or explained it as a result of aging. Regardless
      of physical health, older persons with cognitive impairment have active attitude
      to aging. They could find ways of compensation of cognitive deficits without
      assistance. Patients with vascular dementia could not compensate their cognitive
      deficit even with support.

PMID- 28514555
TI  - [The use of the gender dimorphism index of J. Tanner for assessing the physical
      state of older women].
AB  - Assessment of the physical status of older women conducted anthropometry and
      bioimpendance analysis. Body type determined by the gender dimorphism index of J.
      Tanner (1951). It was found that in the studied sample representative of
      gynecomorphic and mesomorphic body types were determined in a high percentage of
      cases: 46,15 and 49,11 %. Women andromorphic body type were found less frequently
      - 4,74 %. Women with gynecomorphic body type were smaller mass and transverse
      dimensions of the body, unlike representatives with andromorphic and
      gynecomorphic body types. The absolute content of fat and lean body mass tended
      to increase from gynecomorphic body types representatives to andromorphic. The
      results of anthropometric measurements, bioimpedance analysis and determined by
      the gender dimorphism index of J. Tanner provide results about adaptive
      possibilities the human body and can serve as markers (predictors) of somatic
      diseases.

PMID- 28514556
TI  - [The syndrome of falls in the elderly].
AB  - The purpose of the study was to examine the problem of falls in the elderly. A
      prospective cohort study of 537 patients over 65 years using validated
      questionnaires and functional tests. 56,58 % of patients had at least one fall
      event in the 12 months prior to the observation. 82,76 % of all falls are over
      the age of 85 years. Significantly more patients younger than 85 years fell in
      the autumn and winter (to 17,64 and 25,93 %, respectively) and over the age of 85
      years in 50 % of cases (95 % CI 28,2-71,8) fell summer. Polypharmacy and comorbid
      conditions increases the risk of falls. 32,89 % of people over 65 years in the
      fall received fractures. However, a fracture of the femoral neck in 60 % of cases
      diagnosed over the age of 85 years. Hypodynamy observed in 69,77 % of cases.

PMID- 28514557
TI  - [Systemic analysis of factors affecting the quality of life of elderly people
      using different forms of social services].
AB  - The satisfaction of the quality of life (QOL) in elderly age is discussed. There
      have been considered the satisfaction of QOL depending on the form of social
      service in urban and rural areas. The key factors influencing the QOL in various
      forms of services is defined. They include: rural life satisfaction is largely
      dependent on the availability of family than on the health and financial status;
      in a special house for single elderly life satisfaction is determined only by the
      state of health due to the large number of chronic diseases, in stationary social
      services very important factor is loneliness, isolation that creates some feeling
      of being tired of life, depression, provocation the abuse of alcohol.

PMID- 28514558
TI  - [Aging-induced differences in relationships between intelligence and self
      assessment of quality of life].
AB  - Relationships between a self-assessment of quality of life and level of verbal,
      figurative and social intelligence in three age groups of students (middle age
      63,9+/-5,8, 32+/-7,2, and 19,7+/-1,5 years; 90 % women) are studied. The group of
      elderly people differed from younger in low values of an integrated indicator
      physical health according to SF-36 questionnaire, especially - on scales physical
      and role functioning, and decreased figurative and social intelligence at
      relative constancy of verbal IQ. The different age-associated forms of
      interrelation of components of intelligence and quality of life are found:
      positive correlation between social intelligence and role functioning scores at
      senior persons; more numerous positive correlations between verbal and figurative
      intelligence and indicators of quality of life including integrated indicator of
      mental health in the thirty-year-old group; and positive correlation between
      verbal intelligence and values on a scale physical functioning, but negative
      correlations between figurative intelligence and role functioning and between
      social intelligence and an integrated indicator physical health for the twenty
      year-old group. Therefore, continuous education and IQ increasing during
      professional activity and after retirement it is possible to consider as
      prognostic valuable factors of "successful" aging.

PMID- 28514560
TI  - [Organization of beds nursing care as a form of implementation of a comprehensive
      strategy for health and social care elderly people].
AB  - The article tells about one of the actual problem of the provision of medical and
      social care for elderly and old aged people, through the organization of nursing
      care beds in the Voronezh region. Since the beginning of 2014 there were
      organized 320 such beds in 27 medical organizations of the region. Regular
      surveys of patients and their relatives, as well as personnel involved in the
      care service, made it possible to make the necessary adjustments and the further
      expansion of services in other hospitals. Thus the end of 2014 the number of
      nursing beds has been increased to 525, so more than a thousand patients have
      received the necessary nursing care.

PMID- 28514559
TI  - [Quality of life for men of different ages in the russian European North and its
      relationship with self-reported health and hormonal status].
AB  - Assessment of the quality of life for male inhabitants of the Russian European
      North demonstrated decreased indices of physical health component (the scale of
      role functioning determined by physical condition) and mental health component
      (the scales of social functioning and role functioning determined by emotional
      state and mental health) compared to the inhabitants of Siberia as a comparison
      group. Men aged up to 29 had the highest values at all scales. The values
      decreased with age. The most prominent decrease was observed for the scales of
      general well-being and pain intensity. There was a moderate decrease for the
      scales of physical functioning, role functioning determined by emotional state,
      and role functioning determined by physical condition. Quality of life was
      closely related to self-reported health of northerners, pathological index,
      molecular marker of aging, and biological age. Negative correlation between these
      values implies the deterioration of physical and mental health with biological
      age. The quality of life for northerners also correlated with hormonal status.
      There was a relationship between testosterone and three scales of physical health
      components; between cortisol and one scale of physical component; and between
      both dehydroepiandrosterone sulfate and insulin and the scales of physical and
      mental components of health. The effect of various hormones on different age
      groups of northerners was demonstrated.

PMID- 28514561
TI  - [Changing health, activity and mood Department of day care clients comprehensive
      social service center: training program, methods, results].
AB  - The comparative analysis of changes in the self-assessment of health, activity
      and mood of older clients (men and women) separating the daycare center of the
      complex of social services. Used psychodiagnostic method of self-assessment of
      the functional state of the differential "Test SAN" (V.A.Doskin, N.A. Lavrentiev,
      V.B.Sphere, M.P.Miroshnikov). The study of these states conducted before and
      after the implementation of targeted training programs, simulation and which goal
      setting made from the standpoint of the system and subject-activity approach.

PMID- 28514562
TI  - [Actual problems of social gerontology at the present stage of development of
      Russia].
AB  - The basic medico-demographic indices of aging population for Russia were
      identified in this article. Special attention was given to the examination of the
      demographic risks of a reduction in the population at the working ages, to an
      increase in the demographic load on the labor forces. The "Strategy for Action
      for the elderly persons until 2025", prepared by the Interdepartmental Working
      Group at the Ministry of Labour and Social Protection of the Russian Federation,
      was analyzed. The development and implementation of the professional longevity
      management system is one of the timely and comprehensive solutions to the problem
      of employment in the elderly. The need for further studies was proven, dedicated
      to the use of innovative gerontotechnologies in order to prevent the premature
      workability reduction, retarding of the aging processes, the level of mortality
      decrease and the professional longevity increase, especially in the elderly.

PMID- 28514563
TI  - Recent Trends in Kidney Transplant in the United States.
AB  - The number of new wait list registrants has increased in the last decade but not
      to the same magnitude as the increase in the number of end stage renal disease
      patients in the United States. The number of wait list patients has increased at
      a much higher pace due to the lack of kidney supply. The overall number of kidney
      transplants only increased slightly. Paired exchange kidney transplant is a
      viable source of increasing the availability of kidney transplant and also offers
      access to transplant to patients with immunologic barriers to their intended
      donors. Paired donor exchange results in similar outcomes despite recipients'
      having a higher immunologic risk profile. The kidney allocation system (KAS) was
      recently implemented and so far has resulted in more access for patients with
      very high immunologic risk and allocation of lower kidney donor profile index
      organs to younger recipients. Longer follow up is needed to determine the net
      benefit of the KAS.

PMID- 28514564
TI  - MELD Exceptions for Hepatocellular Carcinoma: Regional Variations in the Impact
      of the Share 35 Liver Allocation Policy.
AB  - Historically, the OPTN liver allocation policies have favored candidates listed
      with MELD exception scores, and the use of exceptions has increased each year
      since the inception of the MELD era. The implementation of Share 35 and other
      recent changes in OPTN liver allocation policies have reduced the preference for
      MELD exception candidates to some extent, but the nature and degree of the impact
      appears to vary widely from one region to another. This report emphasizes the
      geographic inequities and regional variations in transplant practices, with a
      focus on liver transplant candidates with hepatocellular carcinoma exceptions,
      and highlights the need for strategies to promote equitable organ distribution
      across geographical regions and patient conditions.

PMID- 28514565
TI  - An Update on Cardiac Transplantation in the United States Based on an Analysis of
      the UNOS Registry.
AB  - Cardiac transplantation remains a viable option for those with end-stage heart
      disease. In the last few years, the number of heart transplants has begun to
      increase slightly. Over the last 27 years, the major reasons for cardiac
      transplant remain coronary artery disease and dilated cardiomyopathy. Currently,
      heart transplants have an average lifespan of 10.5 years. The main United Network
      for Organ Sharing characteristics correlating with poor allograft survival
      include repeat transplantation, ischemic time, post-transplant dialysis, and age
      at the time of transplant. Data over the last two decades shows that late graft
      survival continues to improve slightly. This is primarily a result of a decrease
      in early graft failure. In heart transplant patients, we still need to find ways
      to stop late (>1 year post-transplant) graft loss.

PMID- 28514566
TI  - Long-Term Pancreas Allograft Survival in Simultaneous Pancreas-Kidney
      Transplantation by Era.
AB  - Data collected by the United Network for Organ Sharing from all approved United
      States transplant programs were analyzed; the data included 20,290 adult diabetic
      patients who received primary pancreas transplants between October 1987 and
      December 2014. Simultaneous pancreas-kidney (SPK) transplantation has become the
      major therapeutic option for diabetes patients. The number of SPKs per year has
      not increased since 1999; it leveled off or decreased slightly each year.
      Recipients in the most recent period, 2010-2014, were more likely than recipients
      in any of the other periods to be non-white, older, male, to have had diabetes
      longer, to have higher body mass indices; and in this group there were more donor
      recipient human leukocyte antigen mismatches. Donors in the 2010-2014 period were
      more likely to be younger and male and less likely to be white. Pancreas graft
      survival rates were highest in the 2010-2014 period (one-year graft survival
      89.7%) vs. those for 1987-1989 (74.6%), 1990- 1994 (77.5%), 1995-1999 (82.9%),
      2000-2004 (84.4%), and 2005-2009 (85.5%); the five-year rates were 72.7% for 2010
      14 vs. 60.0%, 64.3%, 69.0%, 70.9%, and 73.9% for the other periods, respectively.
      There was no decreased risk of graft failure for recent-era transplants compared
      with those of 1987-1989, except for those in 2005-2009. By year of transplant,
      the adjusted hazard ratios [with 95% confidence intervals (CI)] for overall loss
      of grafts surviving over one year in eras 1990-1994, 1995-1999, 2000-2004, 2005
      2009, and 2010-2014 were, respectively, 0.85 (CI 0.66-1.09), 0.85 (CI 0.66-
      1.09), 0.87 (CI 0.67-1.13), 0.71 (CI 0.54-0.93), and 0.86 (CI 0.64-1.15). Chronic
      rejection caused 44.9% of graft losses between one and five years and 51.5% after
      five years. There is a need for a means to identify early markers of chronic
      rejection-and to control it-to improve long-term survival.

PMID- 28514567
TI  - Impact of Diabetes Mellitus on Survival Outcome of Lung Transplant Recipients: An
      Analysis of OPTN/UNOS Data.
AB  - BACKGROUND: There are limited data on the outcome of diabetic lung recipients,
      especially in those with new-onset diabetes after transplantation (NODAT).
      METHODS: We studied prevalence of pre-transplant diabetes mellitus (PDM) and
      cumulative incidence of NODAT in lung recipients using the Organ Procurement and
      Transplantation Network /United Network for Organ Sharing database. Between 2004
      and 2011, adult (>=18 years old) recipients transplanted with either first single
      or double-lung were included. Those who lacked a diabetes record or received
      multi-organ transplants were excluded. Patient survival were studied in
      recipients who had functioning grafts for at least one year. Results: There were
      10,226 recipients who had at least one diabetes record, the prevalence of PDM was
      18.25% and the cumulative incidence of NODAT during the five years post
      transplant was 39.43%. Of 9,117 recipients who had functioning grafts for at
      least one year, adjusted hazard ratios (HR) of PDM and NODAT, compared to the
      diabetes-free group, were 1.12 (p=0.048) and 1.12 (p=0.025), respectively.
      Independent risk factors for mortality included the presence of rejection in the
      one year, cytomegalovirus serology donor positive/recipient negative, and
      recipient age >60 years. Among recipients with cystic fibrosis, there was no
      statistical difference in mortality between diabetic recipients and the diabetes
      free group. Compared to the diabetes-free group, the adjusted HRs for mortality
      of PDM and NODAT in recipients without cystic fibrosis were 1.15 (p=0.031) and
      1.14 (p=0.011), respectively. CONCLUSIONS: Diabetes was associated with mortality
      in lung transplant recipients overall and in lung recipients without cystic
      fibrosis. However, there was no association between diabetes and mortality in
      lung recipients with cystic fibrosis.

PMID- 28514568
TI  - The 25th Anniversary of the National Transplantation Pregnancy Registry.
AB  - The National Transplantation Pregnancy Registry (NTPR) is a unique resource for
      comprehensive information about parenthood after transplantation. To date, 1461
      female solid organ transplant recipients with 2609 pregnancies and 879 male
      recipients who fathered 1358 pregnancies have participated in the NTPR. Over the
      first 25 years of the NTPR, pregnancy after transplantation has progressed from a
      situation where termination was once advised, to a topic of pre-transplant
      counselling with likelihood for success if established criteria are met.
      Pregnancy after transplantation remains high-risk; it should be carefully
      considered, planned, and monitored by a multidisciplinary health care team.
      Pregnancy and maternal outcomes vary based on multiple factors, especially on the
      type of organ transplanted and the pre-pregnancy graft function. As an open-ended
      condition-based study, the NTPR accumulates a vast amount of data that is used
      for comparisons that measure the reliability and benefits of treatments and for
      developing state-of-the-art management guidelines based on a review of current
      practices at participating transplant centers. NTPR data analyses have
      contributed to quantifying issues surrounding post-transplant parenthood such as
      location of the transplanted organ in proximity to the developing fetus, the
      safety of various immunosuppressive regimens for pregnancy and fatherhood, the
      teratogenicity of maternal exposure to mycophenolate during pregnancy, the
      advisability and timing of planning a posttransplant pregnancy, the dosing of
      medications during pregnancy, the incidence and treatment of comorbidities during
      pregnancy, and the effect of in utero or breast milk exposure to
      immunosuppressants on the developing child. As the face of transplantation
      evolves, the NTPR will continue to collect and disseminate information to assist
      recipients and their healthcare providers in making informed decisions about the
      advisability of pregnancy and care for those who choose to become parents after a
      solid organ transplant. To insure the continued success of our study, all
      transplant centers and recipients are encouraged to contact the NTPR to report
      any post-transplant pregnancy.

PMID- 28514569
TI  - Hepatitis C and Human Immunodeficiency Virus Kidney Transplantation: The Mount
      Sinai Experience.
AB  - Mount Sinai Hospital in New York has a long history in the field of organ
      transplantation. The first kidney transplant at Mount Sinai was performed in 1967
      by the late Dr. Lewis Burrows and the first laparoscopic donor nephrectomy in New
      York was performed at Mount Sinai in 1996. Over 3000 kidney transplantations have
      been performed at Mount Sinai. In the early 1990s, the first hepatitis C virus
      (HCV) positive patient at Mount Sinai underwent a kidney transplant and the first
      kidney transplant in a patient with human immunodeficiency virus (HIV) in New
      York was performed at Mount Sinai in 2001. In general, these patients have done
      well after renal transplantation, with outcomes similar to those seen in non
      infected patients. This chapter will describe the evolution of immunosuppressive
      regimens in HCV positive and HIV positive patients, and will describe the
      outcomes of kidney transplantation in these patients. Given the favorable
      outcomes, it is reasonable to continue to offer renal transplantation as a
      treatment for end stage renal disease patients with HCV and/or HIV.

PMID- 28514570
TI  - Liver Transplant at the University of Pennsylvania 2015.
AB  - : In this brief report, we summarize activity and trends in liver transplantation
      within the Penn Liver Transplant Program, including total program activity,
      recipient characteristics, waitlist time to transplant, graft and patient
      survival, rate of retransplantation, and multi-organ transplantation activity, as
      well as post-transplant hospital length of stay. RESULTS: Penn Transplant has
      performed 2478 total adult liver transplants to date, consisting of 2382 deceased
      donor liver transplants and 96 living-donor liver transplants. Recipient race is
      approximately 70% white, 20% black, and 10% "other" races including Hispanic,
      Asian, and American Indian/Alaskan Native. Non-cholestatic cirrhosis is the
      leading indication for liver transplantation, accounting for more than half of
      all cases throughout the selected time interval. Most patients are not
      hospitalized at the time of transplantation, and there has been a reduction in
      the number of patients hospitalized in the intensive care unit at the time of
      transplant in the past five years. The median time to transplant is 13.2 months.
      Hazard ratios (HRs) for graft failure after one month, one year, and three years
      post-transplant were reported as: 0.54, 1.05, 1.01 (adult deceased donor) and
      0.58, 0.57, 1.16 (adult living donor); HRs for patient survival were reported as:
      0.44, 1.03, 1.04 (adult deceased donor) and 0.73, 0.74, 0.69 (adult living donor)
      for the same time increments. Penn averaged a 2.3% retransplantation rate and a
      total multi-organ transplant volume of 13. The mean length of hospital stay
      following transplantation was 8.83 days. CONCLUSION: Our program activity data
      mirrors trends that are seen in many of the established busy liver transplant
      centers in the United States. There is greater recognition that liver
      transplantation can be offered to a larger number of candidates who are diagnosed
      with progressive liver failure of primary cancer in the setting of liver
      cirrhosis, and there is an increase in donor organs from either extended criteria
      cadaveric donors or living donors. Despite more complex candidate populations and
      increased utilization of extended criteria donors, Penn's outcomes continue to be
      excellent. We postulate that the future depends on an increase in organ
      procurement organization activity, redesign of the national organ allocation
      system, and expansion of living donor activity.

PMID- 28514571
TI  - ISMETT: An International Collaboration on Organ Transplantation.
AB  - The Institute of the Mediterranean for Transplantation and High Specialty
      Therapies (ISMETT) is a multi-organ transplant and high specialty center located
      in Palermo, Italy and managed by the University of Pittsburgh Medical Center.
      Clinical transplant activity started in 1999 and, herein, we illustrate the
      outcomes achieved over the past 15 years. In total, ISMETT has performed 997
      liver transplants (83.9% adults, 16.1% pediatrics) with a significant percentage
      of liver transplants from cadaver split livers (17%) and partial grafts from
      living donors (11.5%). Among liver transplant recipients, the overall five-year
      graft survival was 74.3% in the adult population and 79% in the pediatric
      population. ISMETT has also performed 419 kidney transplants in total: 211 from
      cadaveric donors (22 double), 176 from living donors, and 32 combined (19 with
      liver, 11 with pancreas, and 2 with heart). The 5-year renal graft survival was
      82.2% (cadaveric donor) and 92.2% (living donor). More recently, in 2005, ISMETT
      started pancreas, lung, and heart transplant programs. In total, 16 pancreas
      transplants have been performed, of which 12 were simultaneous pancreas-kidney
      transplants, 1 was pancreas after kidney, and 3 were pancreas alone transplants.
      One pancreatic islet transplant was also performed in a patient who had already
      undergone kidney transplantation. Patient and pancreas graft survivals at 1 year
      were 86.7% and 73.3%, respectively, and 80% and 73.3% at five years (pancreas
      survival is defined as normoglycemia and insulin-independence). Lung transplant
      has been performed in 133 patients (116 double and 17 single lung). Eleven were
      pediatric (8% of all transplants). The 1-month, 1-year, and 5-year overall graft
      survivals were, 93.8%, 81.4%, and 75.6%, respectively. Heart transplantation has
      been performed in 133 adults (85% were male). Coronary artery disease and
      cardiomyopathy were the leading underlying heart disease diagnoses leading to
      transplant. Mechanical support (ventricular assist device or extracorporeal
      membrane oxygenation) as a bridge to transplant was used in 18% of the heart
      transplant cases. One-year heart graft survival was 83% and 5-year heart graft
      survival was 81%.

PMID- 28514572
TI  - Liver Transplantation in Groningen, The Netherlands: A Single Center Status
      Report.
AB  - The liver transplantation program of the University Medical Center Groningen in
      the Netherlands was started in 1979, making it one of the first programs
      worldwide. During the past 36 years, a total of 1478 liver transplantations have
      been performed, 459 of which were in children. One of the first patients
      transplanted in 1979 is still alive and is one of the longest surviving patients
      after liver transplantation worldwide. During the last decade, an increasing
      number of donation after circulatory death (DCD) donor livers have been accepted
      for transplantation. Over 30% of the livers transplanted in Groningen come from
      DCD donors. These livers have an increased risk of developing biliary
      complications, such as non-anastomotic biliary strictures (NAS). One of the main
      research topics in Groningen has been the pathogenesis and prevention of NAS. In
      an attempt to reduce the incidence of NAS after liver transplantation, machine
      perfusion technology has been developed as an alternative to the traditional
      method of static cold storage. Researchers of the Groningen liver transplant team
      were the first in the world to report a method of ex situ normothermic machine
      perfusion of human donor livers. The efficacy and safety of various types of
      machine perfusion are currently studied in both animal models and clinical
      trials. A second line of research in Groningen focuses on alterations in the
      blood coagulation system in patients with liver disease and undergoing liver
      transplantation. Groningen researchers were the first to describe a 'rebalanced
      state' of the coagulation system in patients with liver disease, making them
      prone to both bleeding and thrombo-embolic complications. Clinicians and
      researchers at the Groningen liver transplant program will continue to
      collaborate with a shared focus and the aim to provide innovation and the highest
      level of care to patients with endstage liver disease.

PMID- 28514573
TI  - Pancreas Transplant at the University of Maryland.
AB  - The characteristic of our diabetic population has been ever changing. No longer
      are our Type 1 diabetics young and thin; they too suffer from the obesity
      epidemic and now present later with the complications of diabetes (renal
      dysfunction, hypoglycemic unawareness, vision loss, neuropathy, etc.). Even with
      all of our medical and technological advances to combat diabetes, there are many
      who are not very well controlled. We evaluated the pancreas transplant recipients
      in the last three years at the University of Maryland to study the outcomes of
      these older and higher body mass index (BMI) recipients, as well as the impact of
      using older and higher BMI donors. We saw no difference in the survival of the
      patient or the allograft of recipients who were older or had higher BMIs. We also
      saw no difference in morbidity for these patients. There also was no difference
      when using older or higher BMI donor organs, longer cold ischemic times,
      different types of donors (donation after cardiac death versus brain dead
      donors), or different types of organs (simultaneous pancreas kidney, pancreas
      transplant alone, or pancreas after kidney). In reviewing our waitlist, our
      patients range widely in age and BMI. As long as they are fit for surgery, we
      will continue to transplant our ever growing population of older and obese
      diabetics without any more adverse outcomes than occur in our normal weight and
      younger patients.

PMID- 28514574
TI  - A Single Center 11 Year Experience with 202 Pancreas Transplants in the New
      Millennium: Evolving Trends.
AB  - : Our single center experience with pancreas transplantation (PTx) over an 11+
      year period is reviewed. METHODS: We retrospectively studied outcomes in 202
      consecutive PTxs in 192 patients at our center. All patients received either
      rabbit anti-thymocyte globulin (rATG) or alemtuzumab (Alem) induction with
      tacrolimus/mycophenolate mofetil and tapered steroids or early withdrawal. 179
      PTxs (89%) were performed with portal-enteric and 23 with systemic-enteric
      drainage. RESULTS: From 11/01 to 3/13, we performed 162 simultaneous kidney-PTxs
      (SKPT), 35 sequential PTxs after kidney, and 5 PTx alone (40 solitary PTxs, SPT).
      186 PTxs (92%) were primary and 16 were pancreas retransplants. With a mean
      follow-up of 5.5 years, overall patient (86% SKPT versus 87% SPT), kidney (74%
      SKPT versus 80% SPT), and pancreas graft survival (both 65%) rates were
      comparable. Causes of PTx loss were also similar between SKPT and SPT; the rates
      of early thrombosis were 8.6% and 5%, respectively. Acute rejection rates were
      similar between groups (SKPT 29% versus SPT 28%, p= not significant). A
      randomized trial of Alem versus rATG induction in SKPT demonstrated lower rates
      of acute rejection and infection in the Alem group. Consequently, Alem induction
      has been used exclusively in all PTxs since 2009. Early steroid elimination has
      been feasible in most patients. Surveillance PTx biopsy-directed
      immunosuppression has contributed to equivalent long-term outcomes in SKPT and
      SPT. Good results have been achieved in African-American patients and in patients
      with a type 2 diabetes phenotype. CONCLUSIONS: Excellent 5-year outcomes
      following PTx can be achieved as >86% of patients are alive, >87% of surviving
      patients are dialysis-free, 80% of surviving patients remain insulin-free, and
      88% of surviving patients have detectable C-peptide levels.

PMID- 28514575
TI  - Alloantibodies in Organ Transplant: A Review of Data Published in 2015.
AB  - In recent years, there have been multiple studies published on longitudinal and
      retrospective analysis of anti-human leukocyte antigen (anti-HLA) antibodies. The
      focus of these reports was to determine specific characteristics of the impact of
      donor specific anti-HLA antibodies (DSA) in organ transplantation. There has been
      a growing concern about DSA in a multitude of organ transplants. Research efforts
      are attempting to gain a better understanding of DSA and possible treatment
      implications for patients with DSA. In 2015, many studies confirm and expand upon
      both the understanding of the humoral theory and the clinical applications of DSA
      in transplantation. This review highlights some of these publications and their
      contributions to the humoral theory of transplantation.

PMID- 28514576
TI  - Advances in Transplantation: Editorial.

PMID- 28514577
TI  - A Review of the Management of Pregnancy After Cardiac Transplantation.
AB  - Success and advances in the management of all aspects of heart disease and heart
      transplantation have allowed for normalcy in life, including the question as to
      the possibility of pregnancy in transplantation. With the growing young adult
      population undergoing heart transplant, pregnancy and transplantation have become
      an issue of importance. Despite the fact that nearly 50 years have passed since
      the first heart transplant, there remains to be little evidence in regard to
      management of pregnant heart transplant recipients. Thus, this review will
      address issues related to pregnancy in this patient population, such as
      preconception counseling, timing and optimization for pregnancy post transplant,
      immunosuppression, cardiac assessment, and management of pregnant heart
      transplant recipients, as well as hemodynamic effects of pregnancy on the
      transplanted heart. Based on the available literature from registrar data, case
      reports and series, with careful planning, monitoring, and appropriate therapies,
      pregnancy in heart transplantation is a viable option in select patients. To
      optimize maternal and fetal outcomes, recommendations are included in this review
      to minimize complications including rejection, graft dysfunction, maternal
      diabetes and hypertension, as well as appropriate changes in immunosuppression.

PMID- 28514578
TI  - Strategies to Improve Novel Drug Development in Kidney Transplantation Through
      the Clinical Trials Process.
AB  - Kidney transplantation has emerged as the preferred treatment for end-stage renal
      disease. Despite excellent short-term outcomes with standard T-cell centric
      immunosuppression, long-term outcomes have not improved. Indeed, approximately
      5,000 renal allografts fail in the United States each year. Until recently, the
      focus on causes for late graft failures was on calcineurin inhibitor toxicity and
      the effects of primary co-morbid conditions (i.e., diabetes and hypertension) or
      recurrent glomerular diseases. However, several recent studies have identified
      donor-specific antibodies and chronic antibody-mediated rejection as the primary
      causes of late allograft failures. This finding has resulted in a renaissance of
      interest in the development of new agents focused on modifying B cells and
      alloantibody responses. In 2015, the Food and Drug Administration (FDA) held a
      conference of experts focused on delineating a path forward for developing a more
      streamlined clinical trials process to obtain labeling for novel agents in
      transplantation. The particular focus was on developing new drugs to deal with
      desensitization and prevention and treatment of antibody-mediated rejection since
      there are currently no approved drugs in this area. In this manuscript, we will
      discuss each of these important issues in depth, with particular focus on how to
      improve the clinical trials process to obtain FDA approval for new drugs that
      would be of benefit to our patients. It is also encouraging that since the FDA
      meeting, two new labeling trials have gone forward and one has already begun
      patient entry.

PMID- 28514579
TI  - Should We Be Performing More Pancreas Transplants?
AB  - Pancreas transplantation can provide insulin independence, improved survival, and
      improved quality of life for patients with diabetes mellitus. However, there has
      been a steady decline in the number of pancreas transplants (either alone or with
      a kidney) performed in the United States over the past decade. This decline has
      occurred despite a steady increase in the number of diabetic patients with end
      stage renal disease on the kidney transplant alone waiting list. This paper will
      review the current status of pancreas transplantation, suggest possible
      explanations for the declining numbers of transplants, highlight current gaps in
      knowledge, and suggest possible future studies and developments aimed at
      increasing the application of this effective therapy.

PMID- 28514580
TI  - Advancing Liver Transplantation.
AB  - Donor organ scarcity remains a major limitation in liver transplantation and
      accounts for a great proportion of wait list mortality. As a result, over the
      past decade, significant efforts have been made to increase the existing donor
      pool. These efforts have, in part, resulted in greater use of liver allografts
      following donation after cardiac death (DCD) along with suboptimal (so-called
      marginal) and extended criteria donors. Improved understanding of the
      pathophysiology underlying the inferior outcomes of the liver allografts procured
      after circulatory arrest has not only resulted in better selection and management
      of DCD donors, but has also helped in the development of mechanical perfusion
      strategies. Currently, there is much excitement surrounding the clinical
      applicability of both hypothermic and normothermic perfusion and the potential to
      impact patient survival and allograft function. Attempts to decrease late
      mortality following liver transplantation have focused on minimization of and use
      of new immunosuppressive medications with specific aims of reducing losses as a
      result of infection, malignancy, and renal failure. Lastly, there has been
      increased emphasis on gaining a better understanding of liver immunology and
      redefining the impact of antibody-mediated rejection on allograft function and
      patient survival.

PMID- 28514581
TI  - Advancing Histocompatibility Testing for Solid Organ Transplantation - What is
      Needed? A Personal Opinion.
AB  - The field of histocompatibility testing has seen significant changes and
      advancements in the past quarter of a century. The introduction of polymerase
      chain reaction amplification into routine human leukocyte antigen (HLA) typing
      has informed us on the magnitude of polymorphism among HLA alleles. Solid phase
      testing for antibodies has provided unparalleled insight into antibody
      specificity and the role of antibody mediated rejection in transplant outcomes.
      Herein, we provide a brief overview of advancements in the field that are
      currently in progress. We also provide our own personal opinion on what is on the
      horizon and the direction in which we think the field should progress.

PMID- 28514582
TI  - There is a Road, No Simple Highway: Envisioning a Path to Better Long-Term Organ
      Transplant Survival.
AB  - The current half-life of a transplanted organ has not improved in a very long
      time. Historical reports on the causes of allograft failure have pointed to a
      plethora of contributing issues. However, in recent years, alloantibody-mediated
      injury has emerged as the major cause of allograft loss. As such, one road to
      advance transplant is to address this problem. There is a hope that new
      treatments can minimize the impact of alloantibody-mediated injury just as T-cell
      directed therapies developed over the last few decades have minimized the impact
      of T-cell mediated rejection on allograft survival. However, these new therapies
      are at least a few years away. While we are unsure how to treat alloantibodies,
      we can certainly do a better job at preventing them. This review will discuss the
      current data surrounding alloantibody-mediated injury and how prevention of
      alloantibodies may be one way to advance transplantation.

PMID- 28514583
TI  - Modernization of Chronic Allograft Injury Research: Better Biomarkers, Better
      Studies, Better Outcomes.
AB  - Despite dramatic improvements in acute rejection rates and short-term allograft
      survival, long-term allograft survival remains unchanged in the modern era,
      largely due to chronic allograft injury, a progressive disease that is common
      across all solid organ transplantation but has no proven treatment. Studies of
      novel diagnostic and therapeutic strategies for chronic allograft injury have
      been relatively sparse, in part due to the time and expense required to conduct
      traditional long-term clinical studies of a variably progressive disease. In this
      article, we review the pathophysiology of chronic allograft injury, including
      recent insights into key mechanisms of the disease. We discuss the barriers to
      progress in chronic allograft injury research and present alternative approaches
      to study design that could accelerate improvements in diagnosis, prevention, or
      treatment of the disease. We integrate these approaches with emerging biomarkers
      and surrogate endpoints into a model clinical study of chronic renal allograft
      injury, providing a framework for modern study design in solid organ
      transplantation.

PMID- 28514585
TI  - Advancing Lung Transplantation.
AB  - Lung transplantation rapidly evolved from an experimental to a conventional
      therapy for patients with end-stage lung disease. In recent years, approximately
      4,000 lung transplants are performed annually worldwide. A shortage of suitable
      donor organs remains the main obstacle to increasing transplant volume. In
      addition, long-term outcomes remain disappointing, and the median survival after
      transplantation is approximately 6 years. Chronic rejection has clearly emerged
      as the leading obstacle to better outcomes beyond the first year after
      transplantation. This generally follows a progressive and relentless course
      culminating in allograft failure and death. Consequently, there is a critical
      need for strategies that delay or prevent the development of chronic rejection,
      and better treatments that halt the progression of chronic rejection. The impact
      of novel interventions is best assessed in the context of multi-center randomized
      controlled trials.

PMID- 28514584
TI  - Kidney Transplant Survival: Transforming Early Post-Transplant Opportunities to
      Long-Term Success.
AB  - Substantial strides have been made in improving the short-term success after
      kidney transplantation. Although there has been some progress, there has not been
      a robust improvement with respect to long-term outcomes. However, there remain
      many potentially modifiable transplant-specific risks to long-term patient and
      graft survival. In this chapter, we detail the current state of five important
      short-term transplant-specific clinical events. The early post-transplant events
      that negatively impact long-term survival discussed in this chapter are: acute T
      cell mediated rejection, acute antibody mediated rejection, delayed graft
      function, post-transplant viral infections, and recurrent and de novo diseases
      after transplantation. This chapter focuses on unmet needs and outlines important
      goals, specific to each of the topics, that hold promise for achieving better
      long-term graft survival in kidney transplant patients. Consistent across all
      five areas are: the need for better standardization and improvement in diagnosis
      and testing, identification of relevant clinical surrogate markers in the design
      of new studies, newer immunosuppressive agents, anti-viral agents and targeted
      therapy for certain diseases, and innovative newer clinical trials. A
      multifaceted approach will further enhance long-term kidney transplant survival.

PMID- 28514586
TI  - BKV Viremia and Development of De Novo DSA in Renal Transplant Recipients.
AB  - BK virus (BKV) viremia is a common complication of kidney transplantation. In
      2008, we enacted a screening protocol to detect BKV infection at our institution.
      The cumulative incidence of BKV viremia at our center is 24%, with most cases
      being detected in the first year post-transplant. We have previously identified
      the development of de novo donor specific antibody as a consequence of BKV
      infection treated with immunosuppression reduction; in this report, we confirm
      our prior findings and extend them to include an association of both Class I and
      Class II antibodies with BKV viremia. While with a median time of 4 years follow
      up there was no difference in patient or allograft survival on the basis of BKV
      viremia. Identification of treatment strategies for BKV that will prevent
      complications such as donor specific antibodies should be a research priority in
      this area.

PMID- 28514587
TI  - BK Virus After Kidney Transplantation: A Review of Screening and Treatment
      Strategies and a Summary of the Massachusetts General Hospital Experience.
AB  - BK virus (BKV) is a common infection encountered after kidney transplantation.
      BKV is associated with a spectrum of manifestations, starting with sub-clinical
      viruria, followed by viremia and BKV-associated nephropathy. Standard of care
      includes routine post-transplant screening for BK viruria and/or viremia. Both
      the Kidney Disease Improving Global Outcomes and the American Society of
      Transplantation Infectious Diseases Community of Practice have published
      screening recommendations. Although they vary slightly, they both highlight the
      importance of early detection with serial screening. Once BK viremia is detected,
      the standard management approach includes a reduction of immunosuppression.
      Guidelines differ slightly about the sequence of the immunosuppression reduction,
      but the end result is the same: lowering the overall immunosuppressive burden in
      the patient with BKV infection. At the Massachusetts General Hospital, from 2007
      to 2009, there was no BKV screening protocol in place. The rate of screening
      during this time period increased from 62% to 81%. A total of 29 of the 243
      patients were diagnosed with BK viremia (11.9%), with 23 identified as a result
      of screening and 6 as a result of testing for graft dysfunction. We developed a
      BKV screening protocol consisting of BKV polymerase chain reaction testing in
      blood starting 2 months after kidney transplantation and every 2 months
      thereafter, continuing through month 24 regardless of the allograft function.
      Additional screening for 6 more months is performed in patients who receive anti
      lymphocyte globulin for the treatment of acute rejection. Finally, all patients
      with otherwise unexplained allograft dysfunction are screened. Currently, work is
      being done investigating the use of mammalian target of rapamycin inhibitors to
      treat BKV infection. Trials are also ongoing evaluating cell-based therapies for
      BKV. Research to develop a vaccine or a direct-acting antiviral agent is in
      critical need and an area of research that should be given high priority.

PMID- 28514588
TI  - Immunologic and Infectious Complications in Highly Sensitized Patients Post
      Kidney Transplantation.
AB  - Desensitization therapies evolved more than a decade ago to deal with the growing
      numbers of highly human leukocyte antigen sensitized patients who have an
      immunologic barrier to successful transplantation. Two protocols have evolved and
      have been adopted for primary desensitization. These include high dose
      intravenous immune globulin (IVIG), plasma exchange + low doses IVIG +/-
      rituximab. These protocols have been very successful and have extended and
      improved the lives of numerous sensitized patients who would otherwise languish
      on dialysis. Despite these successes, problems do exist with desensitization.
      These include the risks for antibody-mediated rejection (ABMR) and infections
      related to increased immunosuppression. Here, we discuss current and evolving
      therapies for the prevention and treatment of ABMR. In addition, we discuss
      current data regarding infection risks, especially BK virus, that may predispose
      patients to development of de novo donor specific antibodies and antibody
      rejection. Novel therapies will also be discussed.

PMID- 28514589
TI  - Complications in Transplantation: Medication Nonadherence.
AB  - Following solid organ transplant, complex, lifelong medication regimens are
      required to prevent allograft rejection. Estimates of medication nonadherence in
      transplant recipients vary and may be as high as 70%. Poor medication adherence
      post transplant has been recognized as a contributing factor to reduced outcomes,
      including rejection, graft loss, and survival. Despite the numerous identified
      approaches for adherence assessment, there remains no gold standard. Ongoing
      efforts to identify optimal immunosuppressant adherence monitoring and measuring
      tools in an attempt to identify at risk populations post transplantation
      continue; however, the link between this information and outcomes remains to be
      discovered. Future adherence studies within the transplant population should
      focus on developing surrogate markers of immunosuppressant therapy adequacy and
      exploring the association amongst this data, adherence interventions, and
      outcomes so that optimal strategies may be identified. Immunosuppressant
      adherence should not be assumed, and interventions aimed a priori will provide
      opportunities to derail the movement of negative health outcomes resulting from
      preventable causes.

PMID- 28514590
TI  - C1q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal
      Transplant Candidates with Donor-Specific Antibodies: High Specificity But Low
      Sensitivity When Predicting Flow Crossmatch.
AB  - In complement dependent cytotoxicity crossmatch negative renal transplant
      candidates with human leukocyte antigen donor-specific antibodies (DSA), both the
      presence of DSA C1q+ and the dominant DSA fluorescence were significantly
      associated with a positive flow cytometry crossmatch (FXM+). The C1q+ assay was
      highly specific, but had low sensitivity when predicting FXM+, so the clinical
      significance of a FXM+ in the absence of DSA C1q+ remains to be clarified in
      future studies.

PMID- 28514591
TI  - Risk Stratification of Human Leukocyte Antigen Class II Donor Specific Antibody
      Positive Patients by Immunoglobulin G Subclasses.
AB  - BACKGROUND: Human leukocyte antigen (HLA) antibodies are a major cause of graft
      loss in mismatched transplant recipients. However, the time to graft loss
      resulting from antibody induced injury is unpredictable. The unpredictable nature
      of antibodies may be related to the subclass of antibodies. In this study, HLA
      immunoglobulin G (IgG) subclasses were investigated to determine whether a unique
      IgG subclass composition could better identify those patients at eminent risk for
      graft loss. METHODS: The serial serum samples from the 57 patients with post
      transplant HLA class II donor specific antibodies (DSA) were tested for the three
      IgG subclasses (IgG1, IgG3, and IgG4). RESULTS: IgG3 and IgG4 were highly
      prevalent in failed patients compared to functioning patients (82 % vs. 34%, 45%
      vs. 20%, respectively). IgG3 development showed a distinct subclass trend between
      failed and functioning patients with poor graft survival (log rank p=0.0006).
      IgG1 was almost equally abundant in both groups (100% and 97%, respectively). Of
      the 5 patterns of IgG subclass combinations observed, IgG1+3+ showed the
      strongest association with graft failure (hazard ratio 3.14, p=0.007).
      CONCLUSION: Patients with IgG3 subclass HLA DSA showed lower graft survival. Post
      transplant monitoring for IgG subclasses rather than total IgG monitoring may
      identify patients at risk for graft failure.

PMID- 28514592
TI  - Soft Skyrmions, Spontaneous Valence and Selection Rules in Nanoparticle
      Superlattices.
AB  - A number of bewildering paradoxes arise in the field of nanoparticle self
      assembly: nominal low density superlattices, strong stability of low coordination
      sites, and a clear but imperfect correlation between lattice stability and the
      maximum of hard sphere packing, despite the fact that that nanocrystals
      themselves are, through their ligands, very much compressible. In this study, I
      show that by regarding nanocrystals as pseudotopological objects ("soft
      skyrmions"), it is possible to identify and classify the ligand textures that
      determine their bonding. These textures consist of interacting vortices, where
      the total vorticity defines a spontaneous valence (coordination). Furthermore,
      skyrmion interactions are governed by two simple assumptions, which lead to a set
      of selection rules for superlattice structure. Besides resolving all the above
      paradoxes, the predictions are completely supported by more than one hundred
      sixty experiments gathered from the literature, including a wide range of
      nanocrystal cores and ligands (saturated or unsaturated hydrocarbons, amines,
      polystyrene, etc.). How those results can be used for addressing more complex
      structures and guiding future experiments is also addressed.

PMID- 28514593
TI  - Thickness Resonance Acoustic Microscopy for Nanomechanical Subsurface Imaging.
AB  - A nondestructive scanning near-field thickness resonance acoustic microscopy
      (SNTRAM) has been developed that provides high-resolution mechanical depth
      sensitivity and sharp phase contrast of subsurface features. In SNTRAM
      technology, we excited the sample at its thickness resonance, at which a sharp
      change in phase is observed and mapped with a scanning probe microscopy stage in
      near field to provide nanometer-scale nanomechanical contrast of subsurface
      features/defects. We reported here the remarkable subsubsurface phase contrast
      and sensitivity of SNTRAM by exciting the sample with a sinusoidal elastic wave
      at a frequency equal to the thickness resonance of the sample. This results in a
      large shift in phase component associated with the bulk longitudinal wave
      propagating through the sample thickness, thus suggesting the usefulness of this
      method for (a) generating better image contrast due to high S/N of the
      transmitted ultrasound wave to the other side of the sample and (b) sensitive
      detection of local variation in material properties at much better resolution due
      to the sharp change in phase. We demonstrated that the sample excited at the
      thickness resonance has a more substantial phase contrast and depth sensitivity
      than that excited at off-resonance and related acoustic techniques. Subsurface
      features down to 5-8 nm lateral resolution have been demonstrated using a
      standard sample.

PMID- 28514595
TI  - Flocculation and Dewatering of Mature Fine Tailings Using Temperature-Responsive
      Cationic Polymers.
AB  - Temperature-responsive copolymer with cationic charge was prepared with N
      isopropylacrylamide (NIPAm) and 2-aminoethyl methacrylamide hydrochloride (AEMA)
      by conventional free-radical polymerization. The flocculation performance of the
      copolymer, poly(AEMA-st-NIPAm), was compared to five different mixture ratios of
      polyNIPAm and cationic poly(acrylamide-st-diallyldimethylammonium chloride)
      (poly(AAm-st-DADMAC)). The effects of polymer mixture ratios, polymer dosages,
      and temperature on solid-liquid separation as a function of initial settling
      rates (ISR), supernatant turbidity, sediment solid content, and water recovery
      were investigated. Poly(NIPAm) can facilitate particles aggregation by bridging
      and hydrogen bonding under lower critical solution temperature (LCST); whereas,
      at temperature above LCST, the adsorption of poly(NIPAm) chains on particles can
      be enhanced by hydrophobic interaction. A two-step (25  degrees C -> 50  degrees
      C -> 25  degrees C) consolidation can further enhance the sediment solid content
      by polyNIPAm. While the neutral property of polyNIPAm resulted in high turbidity
      of supernatant, mixing with poly(AAm-st-DADMAC) increases the clarity of
      supernatant by neutralization of fine particles. The copolymer poly(AEMA-st
      NIPAm) functions as a polyelectrolyte to enhance the polymer adsorption onto
      particles via electrostatic interactions, thus further improving ISR and
      supernatant clarity.

PMID- 28514594
TI  - Quantum Monte Carlo Calculations on a Benchmark Molecule-Metal Surface Reaction:
      H2 + Cu(111).
AB  - Accurate modeling of heterogeneous catalysis requires the availability of highly
      accurate potential energy surfaces. Within density functional theory, these can
      unfortunately-depend heavily on the exchange-correlation functional. High-level
      ab initio calculations, on the other hand, are challenging due to the system size
      and the metallic character of the metal slab. Here, we present a quantum Monte
      Carlo (QMC) study for the benchmark system H2 + Cu(111), focusing on the
      dissociative chemisorption barrier height. These computationally extremely
      challenging ab initio calculations agree to within 1.6 +/- 1.0 kcal/mol with a
      chemically accurate semiempirical value. Remaining errors, such as time-step
      errors and locality errors, are analyzed in detail in order to assess the
      reliability of the results. The benchmark studies presented here are at the
      cutting edge of what is computationally feasible at the present time.
      Illustrating not only the achievable accuracy but also the challenges arising
      within QMC in such a calculation, our study presents a clear picture of where we
      stand at the moment and which approaches might allow for even more accurate
      results in the future.

PMID- 28514596
TI  - Unraveling the Growth Mechanism of Silica Particles in the Stober Method: In Situ
      Seeded Growth Model.
AB  - In this work, we investigated the kinetic balance between ammonia-catalyzed
      hydrolysis of tetraethyl orthosilicate (TEOS) and subsequent condensation over
      the growth of silica particles in the Stober method. Our results reveal that, at
      the initial stage, the reaction is dictated by TEOS hydrolysis to form silanol
      monomers, which is denoted as pathway I and is responsible for nucleation and
      growth of small silica particles via condensation of neighboring silanol monomers
      and siloxane network clusters derived thereafter. Afterward, the reaction is
      dictated by condensation of newly formed silanol monomers onto the earlier formed
      silica particles, which is denoted as pathway II and is responsible for the
      enlargement in size of silica particles. When TEOS hydrolysis is significantly
      promoted, either at high ammonia concentration (>=0.95 M) or at low ammonia
      concentration in the presence of LiOH as secondary catalyst, temporal separation
      of pathways I and II makes the Stober method reminiscent of in situ seeded
      growth. This knowledge advance enables us not only to reconcile the most
      prevailing aggregation-only and monomer-addition models in literature into one
      consistent framework to interpret the Stober process but also to grow
      monodisperse silica particles with sizes in the range 15-230 nm simply but
      precisely regulated by the ammonia concentration with the aid of LiOH.

PMID- 28514597
TI  - A Blocked Linear Method for Optimizing Large Parameter Sets in Variational Monte
      Carlo.
AB  - We present a modification to variational Monte Carlo's linear method optimization
      scheme that addresses a critical memory bottleneck while maintaining
      compatibility with both the traditional ground state variational principle and
      our recently introduced variational principle for excited states. For wave
      function ansatzes with tens of thousands of variables, our modification reduces
      the required memory per parallel process from tens of gigabytes to hundreds of
      megabytes, making the methodology a much better fit for modern supercomputer
      architectures in which data communication and per-process memory consumption are
      primary concerns. We verify the efficacy of the new optimization scheme in small
      molecule tests involving both the Hilbert space Jastrow antisymmetric geminal
      power ansatz and real space multi-Slater Jastrow expansions. Satisfied with its
      performance, we have added the optimizer to the QMCPACK software package, with
      which we test a systematically convergent, nonperturbative approach to excitation
      energies on the example of a Mott-insulating hydrogen ring.

PMID- 28514598
TI  - The communal relation of MTHFR, MTR, ACE gene polymorphisms and
      hyperhomocysteinemia as conceivable risk of coronary artery disease.
AB  - Homocysteine and its modulating genes have strongly emerged as novel biomarkers
      for coronary artery disease (CAD). In the present study, we investigated whether
      polymorphisms in homocysteine pathway genes and the plasma levels of
      homocysteine, folate, and vitamin B12, independently or in combination, are
      associated with CAD risk. A total of 504 participants were recruited (cases, n =
      254; controls, n = 250, respectively). Tetra primer allele refractory mutation
      system polymerase chain reaction (PCR) was used for resolving the genotypes of
      5'10' methylenetetrahydrofolate reductase 'MTHFR' polymorphisms (rs1801133,
      rs1801131), 5' methyl tetrahydrofolate homocysteine methyltransferase 'MTR'
      polymorphism (rs1805087), paroxanse1 'PON1' polymorphism (rs662), and
      cystathionine beta synthase 'CBS' polymorphism (rs5742905). Conventional PCR
      amplification was carried out for resolving angiotensin converting enzyme 'ACE'
      insertion/deletion (I/D) polymorphism (rs4646994). ANOVA analysis, adjusted for
      the covariates, revealed that rs1801133, rs1805087 polymorphisms and homocysteine
      levels were associated with CAD. Logistic regression analysis (adjusted) revealed
      similar findings. Logistic regression analysis after applying factorial design to
      the studied single nucleotide polymorphisms (SNPs) revealed that homocysteine
      levels and heterozygous and mutant alleles at rs1801133, rs1805087, along with
      mutant alleles at rs1801131, rs4646994, conferred higher risk for CAD. Our
      results provide insight into the multifactorial nature of coronary artery
      disease. We highlight that SNPs in folate pathway genes and homocysteine have
      role in disease causation and can be used in disease prediction strategies.

PMID- 28514599
TI  - A bioenergetics systems evaluation of ketogenic diet liver effects.
AB  - Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body
      production. To further evaluate how ketogenic diets affect hepatocyte
      bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice
      maintained for 1 month on a ketogenic or standard chow diet. Compared with the
      standard diet, the ketogenic diet increased cytosolic and mitochondrial protein
      acetylation and also altered protein succinylation patterns. SIRT3 protein
      decreased while SIRT5 protein increased, and gluconeogenesis, oxidative
      phosphorylation, and mitochondrial biogenesis pathway proteins were variably and
      likely strategically altered. The pattern of changes observed can be used to
      inform a broader systems overview of how ketogenic diets affect liver
      bioenergetics.

PMID- 28514600
TI  - Evaluating five different loci (rbcL, rpoB, rpoC1, matK, and ITS) for DNA
      barcoding of Indian orchids.
AB  - Orchidaceae, one of the largest families of angiosperms, is represented in India
      by 1600 species distributed in diverse habitats. Orchids are in high demand owing
      to their beautiful flowers and therapeutic properties. Overexploitation and
      habitat destruction have made many orchid species endangered. In the absence of
      effective identification methods, illicit trade of orchids continues unabated.
      Considering DNA barcoding as a potential identification tool, species
      discrimination capability of five loci, ITS, matK, rbcL, rpoB, and rpoC1, was
      tested in 393 accessions of 94 Indian orchid species belonging to 47 genera,
      including one listed in Appendix I of CITES and 26 medicinal species. ITS
      provided the highest species discrimination rate of 94.9%. While, among the
      chloroplast loci, matK provided the highest species discrimination rate of 85.7%.
      None of the tested loci individually discriminated 100% of the species.
      Therefore, multi-locus combinations of up to five loci were tested for their
      species resolution capability. Among two-locus combinations, the maximum species
      resolution (86.7%) was provided by ITS+matK. ITS and matK sequences of the
      medicinal orchids were species specific, thus providing unique molecular
      identification tags for their identification and detection. These observations
      emphasize the need for the inclusion of ITS in the core barcode for plants,
      whenever required and available.

PMID- 28514602
TI  - Informed Consent.

PMID- 28514603
TI  - Case 15-2017 - A 27-Year-Old Woman with Anemia, Thrombocytosis, and Skin Lesions
      after Travel Abroad.

PMID- 28514605
TI  - Physiological Effects of Chronic Hypoxia.

PMID- 28514606
TI  - IDH2 Mutation in a Patient with Metastatic Colon Cancer.

PMID- 28514607
TI  - Tuberous Sclerosis Complex.

PMID- 28514608
TI  - The Committed Perspective - Policy Principles for Regional Health Plans.

PMID- 28514601
TI  - Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis.
AB  - BACKGROUND: Eosinophilic granulomatosis with polyangiitis is an eosinophilic
      vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood
      eosinophil counts and may have value in the treatment of eosinophilic
      granulomatosis with polyangiitis. METHODS: In this multicenter, double-blind,
      parallel-group, phase 3 trial, we randomly assigned participants with relapsing
      or refractory eosinophilic granulomatosis with polyangiitis who had received
      treatment for at least 4 weeks and were taking a stable prednisolone or
      prednisone dose to receive 300 mg of mepolizumab or placebo, administered
      subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary
      end points were the accrued weeks of remission over a 52-week period, according
      to categorical quantification, and the proportion of participants in remission at
      both week 36 and week 48. Secondary end points included the time to first relapse
      and the average daily glucocorticoid dose (during weeks 48 through 52). The
      annualized relapse rate and safety were assessed. RESULTS: A total of 136
      participants underwent randomization, with 68 participants assigned to receive
      mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly
      more accrued weeks of remission than placebo (28% vs. 3% of the participants had
      >=24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI],
      2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at
      both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56;
      P<0.001). Remission did not occur in 47% of the participants in the mepolizumab
      group versus 81% of those in the placebo group. The annualized relapse rate was
      1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate
      ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants
      in the mepolizumab group, as compared with 7% of those in the placebo group, had
      an average daily dose of prednisolone or prednisone of 4.0 mg or less per day
      during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The
      safety profile of mepolizumab was similar to that observed in previous studies.
      CONCLUSIONS: In participants with eosinophilic granulomatosis with polyangiitis,
      mepolizumab resulted in significantly more weeks in remission and a higher
      proportion of participants in remission than did placebo, thus allowing for
      reduced glucocorticoid use. Even so, only approximately half the participants
      treated with mepolizumab had protocol-defined remission. (Funded by
      GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases;
      ClinicalTrials.gov number, NCT02020889 .).

PMID- 28514609
TI  - Letter to a Young Female Physician.

PMID- 28514610
TI  - Osimertinib in EGFR T790M-Positive Lung Cancer.

PMID- 28514611
TI  - Osimertinib in EGFR T790M-Positive Lung Cancer.

PMID- 28514612
TI  - Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17
      Blockade.

PMID- 28514614
TI  - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.

PMID- 28514615
TI  - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.

PMID- 28514613
TI  - KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma.
AB  - BACKGROUND: Mast cells are present in the airways of patients who have severe
      asthma despite glucocorticoid treatment; these cells are associated with disease
      characteristics including poor quality of life and inadequate asthma control.
      Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We
      conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT
      inhibitor, on airway hyperresponsiveness, a physiological marker of severe
      asthma, as well as on airway mast-cell numbers and activation in patients with
      severe asthma. METHODS: We conducted a randomized, double-blind, placebo
      controlled, 24-week trial of imatinib in patients with poorly controlled severe
      asthma who had airway hyperresponsiveness despite receiving maximal medical
      therapy. The primary end point was the change in airway hyperresponsiveness,
      measured as the concentration of methacholine required to decrease the forced
      expiratory volume in 1 second by 20% (PC20). Patients also underwent
      bronchoscopy. RESULTS: Among the 62 patients who underwent randomization,
      imatinib treatment reduced airway hyperresponsiveness to a greater extent than
      did placebo. At 6 months, the methacholine PC20 increased by a mean (+/-SD) of
      1.73+/-0.60 doubling doses in the imatinib group, as compared with 1.07+/-0.60
      doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of
      serum tryptase, a marker of mast-cell activation, to a greater extent than did
      placebo (decrease of 2.02+/-2.32 vs. 0.56+/-1.39 ng per milliliter, P=0.02).
      Airway mast-cell counts declined in both groups. Muscle cramps and
      hypophosphatemia were more common in the imatinib group than in the placebo
      group. CONCLUSIONS: In patients with severe asthma, imatinib decreased airway
      hyperresponsiveness, mast-cell counts, and tryptase release. These results
      suggest that KIT-dependent processes and mast cells contribute to the
      pathobiologic basis of severe asthma. (Funded by the National Institutes of
      Health and others; ClinicalTrials.gov number, NCT01097694 .).

PMID- 28514616
TI  - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.

PMID- 28514617
TI  - Scarlet Fever.

PMID- 28514619
TI  - Targeting Eosinophils in Eosinophilic Granulomatosis with Polyangiitis.

PMID- 28514618
TI  - Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.
AB  - BACKGROUND: Obesity causes frailty in older adults; however, weight loss might
      accelerate age-related loss of muscle and bone mass and resultant sarcopenia and
      osteopenia. METHODS: In this clinical trial involving 160 obese older adults, we
      evaluated the effectiveness of several exercise modes in reversing frailty and
      preventing reduction in muscle and bone mass induced by weight loss. Participants
      were randomly assigned to a weight-management program plus one of three exercise
      programs - aerobic training, resistance training, or combined aerobic and
      resistance training - or to a control group (no weight-management or exercise
      program). The primary outcome was the change in Physical Performance Test score
      from baseline to 6 months (scores range from 0 to 36 points; higher scores
      indicate better performance). Secondary outcomes included changes in other
      frailty measures, body composition, bone mineral density, and physical functions.
      RESULTS: A total of 141 participants completed the study. The Physical
      Performance Test score increased more in the combination group than in the
      aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to
      33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively;
      P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all
      exercise groups than in the control group (P<0.001 for between-group
      comparisons). Peak oxygen consumption (milliliters per kilogram of body weight
      per minute) increased more in the combination and aerobic groups (17.2 to 20.3
      [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the
      resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons).
      Strength increased more in the combination and resistance groups (272 to 320 kg
      [18% increase] and 288 to 337 kg [19% increase], respectively) than in the
      aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body
      weight decreased by 9% in all exercise groups but did not change significantly in
      the control group. Lean mass decreased less in the combination and resistance
      groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1
      kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone
      mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1%
      decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991
      [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events
      included musculoskeletal injuries. CONCLUSIONS: Of the methods tested, weight
      loss plus combined aerobic and resistance exercise was the most effective in
      improving functional status of obese older adults. (Funded by the National
      Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).

PMID- 28514620
TI  - Registry-Based Surveillance of Medical-Device Safety.

PMID- 28514621
TI  - Registry-Based Surveillance of Medical-Device Safety.

PMID- 28514622
TI  - Mast Cells and KIT as Potential Therapeutic Targets in Severe Asthma.

PMID- 28514623
TI  - A 21st-Century Health IT System - Creating a Real-World Information Economy.

PMID- 28514626
TI  - Influence of Early Reproductive Success on Longevity and Late Reproductive
      Success in an Alpine Ungulate.
AB  - The life-history theories of aging predict lifetime trade-offs between early
      reproductive allocation and late-life survival, reproduction, or both components
      of fitness. Recent studies in wild populations have found evidence for these
      early-late life trade-offs, but rarely have they been found across multiple
      traits while exploring the additional effects of variation in environmental
      conditions and individual quality. Benefiting from longitudinal data on adult
      female mountain goats (Oreamnos americanus), we investigated the influence of age
      at first reproduction (AFR) and early reproductive success (ERS) on longevity,
      late reproductive success, and senescence rates while accounting for the
      influence of natal environmental conditions and individual quality. Contrary to
      predictions, we did not find evidence for early-late life trade-offs. Instead, an
      earlier AFR and a greater ERS had positive but weak direct effects on late
      reproductive success. Natal population density, however, was the strongest
      determinant of all life-history traits, having a direct negative effect on female
      longevity, late reproductive success, AFR, and ERS. Although natal density
      reduced the probability of annual reproduction and annual survival during
      adulthood, higher allocation to reproduction in early life and poorer natal
      conditions did not lead to accelerated rates of senescence during adulthood. The
      results of this investigation provide an integrated picture of early-late life
      trade-offs, underscoring the importance of accounting for environmental
      conditions because of their potentially strong implications for population
      dynamics.

PMID- 28514625
TI  - "Latitudinal Gradients in Species Diversity": Reflections on Pianka's 1966
      Article and a Look Forward.

PMID- 28514628
TI  - A Modest Proposal for Unifying Macroevolution and Ecosystem Ecology.

PMID- 28514627
TI  - What Kind of Maternal Effects Can Be Selected For in Fluctuating Environments?
AB  - Just as phenotypic plasticity can evolve when developing individuals get
      informational cues about their future adult environment, deterministic maternal
      effects, where offspring trait values depend on the maternal environment, can
      evolve when mothers gain reliable information about the environments their
      offspring will face. Randomizing maternal effects (a type of diversifying bet
      hedging), where offspring trait values are randomized, can evolve by natural
      selection even when information about future environments is unavailable. We
      investigate selection on both randomizing and deterministic maternal effects in
      environments that show correlated fluctuations between two environmental states.
      We compare the strength of selection for deterministic and randomizing maternal
      effects and explicitly consider maternal fitness costs of producing offspring
      with different phenotypes. Only a small set of environmental parameters allow
      randomizing maternal effects to outcompete deterministic maternal effects; not
      only must there be little or no information available about future environments,
      but the frequency of each environment must fall within a narrow range. By
      contrast, deterministic maternal effects can always invade an ancestral state
      lacking a maternal effect even if the amount of environmental information
      available is low. The long-term outcome may involve offspring trait value
      randomization but only if trait values first evolve to cause extreme differences
      in environment-specific fitness. Overall, deterministic maternal effects are more
      likely to evolve by natural selection than randomizing maternal effects.

PMID- 28514629
TI  - The Emergent Properties of Conspecific Attraction Can Limit a Species' Ability to
      Track Environmental Change.
AB  - Multiple biotic, abiotic, and evolutionary constraints interact to determine a
      species' range. However, most species are not present in all suitable and
      accessible locations. Dispersal ability may explain why many species do not
      occupy all suitable habitat, but highly mobile species also exhibit a mismatch.
      Habitat selection behavior where individuals are site faithful and settle near
      conspecifics could create a social pressure that make a species' geographic range
      resistant to change. We investigated this possibility by using an individual
      based model of habitat selection where habitat quality moved each year. Our model
      demonstrated the benefits of conspecific attraction in relatively stable
      environments and its detrimental influence when habitat quality shifted rapidly.
      These results were most apparent when adult survival was high, because site
      fidelity led to more individuals occupying poor-quality habitat areas as habitat
      quality changed. These individuals attracted other dispersing individuals,
      thereby decreasing the ability to track shifts in habitat quality, which we refer
      to as "social inertia." Consequently, social inertia may arise for species that
      exhibit site fidelity and conspecific attraction, which may have conservation
      implications in light of climate change and widespread alteration of natural
      habitats.

PMID- 28514630
TI  - Speciation and the Latitudinal Diversity Gradient: Insights from the Global
      Distribution of Endemic Fish.
AB  - The nearly universal pattern that species richness increases from the poles to
      the equator (the latitudinal diversity gradient [LDG]) has been of intense
      interest since its discovery by early natural-history explorers. Among the many
      hypotheses proposed to explain the LDG, latitudinal variation in (1)
      productivity, (2) time and area available for diversification, and (3) speciation
      and/or extinction rates have recently received the most attention. Because
      tropical regions are older and were formerly more widespread, these factors are
      often intertwined, hampering efforts to distinguish their relative contributions
      to the LDG. Here we examine the global distribution of endemic lake fishes to
      determine how lake age, area, and latitude each affect the probability of
      speciation and the extent of diversification occurring within a lake. We analyzed
      the distribution of endemic fishes worldwide (1,933 species and subspecies from
      47 families in 2,746 lakes) and find that the probability of a lake containing an
      endemic species and the total number of endemics per lake increase with lake age
      and area and decrease with latitude. Moreover, the geographic locations of
      endemics in 34 of 41 families are found at lower latitudes than those of
      nonendemics. We propose that the greater diversification of fish at low latitudes
      may be driven in part by ecological opportunities promoted by tropical climates
      and by the coevolution of species interactions.

PMID- 28514631
TI  - The Hawk-Eyed Songbird: Retinal Morphology, Eye Shape, and Visual Fields of an
      Aerial Insectivore.
AB  - Swallows are a unique group of songbirds because they are active-pursuit
      predators that execute all aspects of hunting prey in flight: search, detection,
      pursuit, and capture. We show that swallows have evolved a visual system that is
      unlike that of any other studied songbird. Swallows have a bifoveate retina that
      provides sharp lateral and frontal vision, an unusually long eye that enhances
      spatial resolution, a large posterior blind area, and a narrow binocular field.
      We also show that swallows and diurnal raptors (hawks and falcons) have converged
      on a similar visual configuration but that, interestingly, predatory songbirds
      that ambush prey (flycatchers) have not converged on the same suite of traits.
      Despite the commonly held belief that predators rely on binocular vision, the
      temporal (frontally projecting) fovea present in swallows-but not present in
      other songbirds-is likely not involved in binocular vision. Instead, swallows
      have four nonoverlapping foveae in a 100 degrees  arc around the beak, which can
      improve the tracking of frontally located aerial prey that are engaging in
      evasive maneuvers. Overall, vision in pursuit predators reflects the complex
      sensory demands of hunting in the air at high speeds and emphasizes the
      importance of acute frontal vision in predators.

PMID- 28514632
TI  - A Waterborne Pursuit-Deterrent Signal Deployed by a Sea Urchin.
AB  - Selection by consumers has led to the evolution of a vast array of defenses in
      animals and plants. These defenses include physical structures, behaviors, and
      chemical signals that mediate interactions with predators. Some of the strangest
      defensive structures in nature are the globiferous pedicellariae of the
      echinoderms. These are small venomous appendages with jaws and teeth that cover
      the test of many sea urchins and sea stars. In this study, we report a unique use
      of these defensive structures by the collector sea urchin Tripneustes gratilla.
      In both the laboratory and the field, globiferous pedicellariae were unpalatable
      to fish consumers. When subject to simulated predator attack, sea urchins
      released a cloud of pedicellaria heads into the water column. Flume experiments
      established the presence of a waterborne cue associated with this release of
      pedicellariae that is deterrent to predatory fish. These novel results add to our
      understanding of how the ecosystem-shaping sea urchin T. gratilla is able to
      reach high densities in many reef habitats, with subsequent impacts on algal
      cover.

PMID- 28514633
TI  - Why Have Multiple Plastic Responses? Interactions between Color Change and Heat
      Avoidance Behavior in Battus philenor Larvae.
AB  - Having multiple plastic responses to a change in the environment, such as
      increased temperature, can be adaptive for two major reasons: synergy (the
      plastic responses perform better when expressed simultaneously) or
      complementarity (each plastic response provides a greater net benefit in a
      different environmental context). We investigated these hypotheses for two forms
      of temperature-induced plasticity of Battus philenor caterpillars in southern
      Arizona populations: color change (from black to red at high temperatures) and
      heat avoidance behavior (movement from host to elevated refuges at high host
      temperatures). Field assays using aluminum models showed that the cooling effect
      of the red color is greatly reduced in a refuge position relative to that on a
      host. Field assays with live caterpillars demonstrated that refuge seeking is
      much more important for survival under hot conditions than coloration; however,
      in those assays, red coloration reduced the need to seek refuges. Our results
      support the complementarity hypothesis: refuge seeking facilitates survival
      during daily temperature peaks, while color change reduces the need to leave the
      host over longer warm periods. We propose that combinations of rapid but costly
      short-term behavioral responses and slow but efficient long-term morphological
      responses may be common when coping with temperature change.

PMID- 28514634
TI  - Convergent Reversion to Single Mating in a Wasp Social Parasite.
AB  - While eusociality arose in species with single-mating females, multiple mating by
      queens has evolved repeatedly across the social ants, bees, and wasps.
      Understanding the benefits and costs of multiple mating of queens is important
      because polyandry results in reduced relatedness between siblings, reducing kin
      selected benefits of helping while also selecting for secondary social traits
      that reduce intracolony conflict. The leading hypothesis for the benefits of
      polyandry in social insects emphasizes advantages of a genetically diverse
      workforce. Workerless social parasite species (inquilines) provide a unique
      opportunity to test this hypothesis, since they are derived from social ancestors
      but do not produce workers of their own. Such parasites are thus predicted to
      evolve single mating because they would experience the costs of multiple mating
      but not the benefits if such benefits accrue through the production of a
      genetically diverse group of workers. Here we show that the workerless social
      parasite Dolichovespula arctica, a derived parasite of wasps, has reverted to
      obligate single mating from a facultatively polyandrous ancestor, mirroring a
      similar reversion from obligate polyandry to approximate monandry in a social
      parasite of fungus-farming ants. This finding and a comparison with two other
      cases where inquilinism did not induce reversal to monandry support the
      hypothesis that facultative polyandry can be costly and may be maintained by
      benefits of a genetically diverse workforce.

PMID- 28514635
TI  - Specialization to Extremely Low-Nutrient Soils Limits the Nutritional
      Adaptability of Plant Lineages.
AB  - Specialization to extreme selective situations promotes the acquisition of traits
      whose coadaptive integration may compromise evolutionary flexibility and
      adaptability. We test this idea in the context of the foliar stoichiometry of
      plants native to the South African Cape. Whereas foliar concentrations of
      nitrogen, phosphorus (P), potassium (K), calcium, magnesium, and sodium showed
      strong phylogenetic signal, as did the foliar ratios of these nutrients to P, the
      same was not true of the corresponding soil values. In addition, although foliar
      traits were often related to soil values, the coefficients of determination were
      consistently low. These results identify foliar stoichiometry as having a strong
      genetic component, with variation in foliar nutrient concentrations, especially
      [P] and [K], being identified as potentially adaptive. Comparison of
      stoichiometric variation across 11 similarly aged clades revealed consistently
      low foliar nutrient concentrations in lineages showing specialization to
      extremely low-nutrient fynbos heathlands. These lineages also display lower rates
      of evolution of these traits as well as a reduced tendency for foliar [P] to
      track soil [P]. Reduced evolutionary lability and adaptability in the nutritional
      traits of fynbos-specialist lineages may explain the floristic distinctness of
      the fynbos flora and implies a reduced scope for edaphically driven ecological
      speciation.

PMID- 28514637
TI  - Re-examining the Causes and Meaning of the Risk Allocation Hypothesis.
AB  - The risk allocation hypothesis has inspired numerous studies seeking to
      understand how temporal variation in predation risk affects prey foraging
      behavior, but there has been debate about its generality and causes. I examined
      how imperfect information affects its predictions and sought to clarify the
      causes of the predicted patterns. I first confirmed that my modeling approach
      given a threshold or linear fitness function-produced the risk allocation
      prediction that prey increase their foraging efforts during low and high risk as
      the proportion of high-risk periods increases. However, the causes of this result
      and its robustness differed for the two fitness functions. When prey that had
      evolved to use perfect information received imperfect information, risk
      allocation was reduced. However, prey that evolved to use imperfect information
      in some cases reversed the risk allocation prediction. The model also showed that
      risk allocation occurs even when prey have no knowledge that the proportions of
      low- and high-risk periods have changed. I conclude that risk allocation is
      largely not driven by prey expectations about future states of the environment
      but rather by the prey's current energetic state and time remaining. I discuss
      the consequences for experimental design and explanations for empirical results.

PMID- 28514636
TI  - Eco-Evolutionary Theory and Insect Outbreaks.
AB  - Eco-evolutionary theory argues that population cycles in consumer-resource
      interactions are partly driven by natural selection, such that changes in
      densities and changes in trait values are mutually reinforcing. Evidence that the
      theory explains cycles in nature, however, is almost nonexistent. Experimental
      tests of model assumptions are logistically impractical for most organisms, while
      for others, evidence that population cycles occur in nature is lacking. For
      insect baculoviruses in contrast, tests of model assumptions are straightforward,
      and there is strong evidence that baculoviruses help drive population cycles in
      many insects, including the gypsy moth that we study here. We therefore used
      field experiments with the gypsy moth baculovirus to test two key assumptions of
      eco-evolutionary models of host-pathogen population cycles: that reduced host
      infection risk is heritable and that it is costly. Our experiments confirm both
      assumptions, and inserting parameters estimated from our data into eco
      evolutionary insect-outbreak models gives cycles closely resembling gypsy moth
      outbreak cycles in North America, whereas standard models predict unrealistic
      stable equilibria. Our work shows that eco-evolutionary models are useful for
      explaining outbreaks of forest insect defoliators, while widespread observations
      of intense selection on defoliators in nature and of heritable and costly
      resistance in defoliators in the lab together suggest that eco-evolutionary
      dynamics may play a general role in defoliator outbreaks.

PMID- 28514639
TI  - Warming-Induced Changes to Body Size Stabilize Consumer-Resource Dynamics.
AB  - Both body size and temperature directly influence consumer-resource dynamics.
      There is also widespread empirical evidence for the temperature-size rule (TSR),
      which creates a negative relationship between temperature and body size. However,
      it is not known how the TSR affects community dynamics. Here we integrate
      temperature- and size-dependent models to include indirect effects of warming,
      through changes in body size, to answer the question, How does the TSR affect the
      predicted response of consumer-resource systems to warming? We find that the TSR
      is expected to maintain consumer-resource biomass ratios and buffer the community
      from extinctions under warming. While our results are limited to conditions where
      organisms are below their thermal optimum, they hold under a range of realistic
      temperature-size responses and are robust to the type of functional response. Our
      analyses suggest that the widely observed TSR may reduce the impacts of warming
      on consumer-resource systems.

PMID- 28514638
TI  - The Evolution of Cooperation: Interacting Phenotypes among Social Partners.
AB  - Models of cooperation among nonkin suggest that social assortment is important
      for the evolution of cooperation. Theory predicts that interacting phenotypes,
      whereby an individual's behavior depends on the behavior of its social partners,
      can drive such social assortment. We measured repeated indirect genetic effects
      (IGEs) during cooperative predator inspection in eight populations of Trinidadian
      guppies (Poecilia reticulata) that vary in their evolutionary history of
      predation. Four broad patterns emerged that were dependent on river, predation
      history, and sex: (i) current partner behavior had the largest effect on focal
      behavior, with fish from low-predation habitats responding more to their social
      partners than fish from high-predation habitats; (ii) different focal/partner
      behavior combinations can generate cooperation; (iii) some high-predation fish
      exhibited carryover effects across social partners; and (iv) high-predation fish
      were more risk averse. These results provide the first large-scale comparison of
      interacting phenotypes during cooperation across wild animal populations,
      highlighting the potential importance of IGEs in maintaining cooperation.
      Intriguingly, while focal fish responded strongly to current social partners,
      carryover effects between social partners suggest generalized reciprocity (in
      which one helps anyone if helped by someone) may contribute to the evolution of
      cooperation in some, but not all, populations of guppies.

PMID- 28514640
TI  - Digital disruption 'syndromes' in a hospital: important considerations for the
      quality and safety of patient care during rapid digital transformation.
AB  - The digital transformation of hospitals in Australia is occurring rapidly in
      order to facilitate innovation and improve efficiency. Rapid transformation can
      cause temporary disruption of hospital workflows and staff as processes are
      adapted to the new digital workflows. The aim of this paper is to outline various
      types of digital disruption and some strategies for effective management. A large
      tertiary university hospital recently underwent a rapid, successful roll-out of
      an integrated electronic medical record (EMR). We observed this transformation
      and propose several digital disruption "syndromes" to assist with understanding
      and management during digital transformation: digital deceleration, digital
      transparency, digital hypervigilance, data discordance, digital churn and post
      digital 'depression'. These 'syndromes' are defined and discussed in detail.
      Successful management of this temporary digital disruption is important to ensure
      a successful transition to a digital platform.

PMID- 28514641
TI  - Mapping workforce configuration and operational models in Australian emergency
      departments: a national survey.
AB  - Objective Hospital emergency departments (ED) in Australia and internationally
      have been experiencing increased demand, resulting in reduced hospital quality,
      impaired access and adverse health outcomes. Effective evaluation of new ED
      service models and their effect on outcomes is reliant on baseline measures of
      the staffing configuration and organisational characteristics of the EDs being
      studied. The aim of the present study was to comprehensively measure these
      variables in Australian EDs. Methods Australian hospital EDs with 24-h medical
      and nursing cover were identified and invited to participate in the study.
      Telephone interviews were conducted with nursing or medical department managers
      to collect data related to hospital characteristics, ED workforce and training
      and ED service and operational models. Results Surveys were completed in 87% of
      the population sample (n=135). Metropolitan EDs were significantly more likely to
      retain higher full-time equivalents (FTEs) in several medical (staff specialist,
      registrar, resident and intern) and nursing (nurse practitioner (NP), nurse
      educator, nurse unit manager and registered nurse) positions. NPs were employed
      by 52% of Australian EDs overall, but this ranged from 40% to 75% depending on
      jurisdiction. The most commonly used operational models were FastTrack teams (72%
      of EDs), short-stay/observational unit (59%) and patient liaison models for aged
      care (84%) and mental health (61%). EDs that employed NPs were significantly more
      likely to use FastTrack (P=0.002). Allied health services most frequently
      available within these EDs were radiology (60%), social work (69%), physiotherapy
      (70%) and pharmacy (65%). Conclusions The present study has established a
      baseline measure of the staffing configuration and organisational characteristics
      of Australian EDs. What is known about the topic? EDs are overcrowded due, in
      part, to the combined effect of increased service demand and access block.
      Innovative service and workforce models have been implemented by health
      departments aiming to improve service and performance. National uptake of these
      service and workforce innovations is unknown. What does this paper add? The
      present study is the most comprehensive to date profiling Australian EDs covering
      hospital characteristics, workforce configuration, operational models and NP
      service patterns and practice. What are the implications for practitioners?
      Information from the present study will assist health service planners to
      evaluate workforce and service reform models, and to monitor trends in emergency
      service development.

PMID- 28514642
TI  - Congenital adrenal hyperplasia due to 11-hydroxylase deficiency-Compound
      heterozygous mutations of a prevalent and two novel CYP11B1 mutations.
AB  - 11beta-hydroxylase deficiency (11beta-OHD) occurs in about 5-8% of congenital
      adrenal hyperplasia (CAH). In this study, we identified three CYP11B1 (encoding
      Cytochrome P450 11B1) heterozygous mutations: c.1358G>C (p.R453Q), c.1229T>G
      (p.L410R) and c.1231G>T (p.G411C) in a Chinese CAH patient due to classic 11beta
      OHD. His parents were healthy and respectively carried the prevalent mutation
      c.1358G>C (p.R453Q), and the two novel mutations c.1229T>G (p.L410R) and
      c.1231G>T (p.G411C). In vitro expression studies, immunofluorescence demonstrated
      that wild type and mutant (L410R and G411C) proteins of CYP11B1 were correctly
      expressed on the mitochondria, and enzyme activity assay revealed the mutant
      reduced the 11-hydroxylase activity to 10% (P<0.001) for the conversion of 11beta
      deoxycortisol to cortisol. Subsequently, three dimensional homology models for
      the normal and mutant proteins were built by using the x-ray structure of the
      human CYP11B2 as a template. Interestingly, in the heme binding site I helix, a
      change from helix to loop in four amino acide took place in the mutant model. In
      conclusion, this study expands the spectrum of mutations in CYP11B1 causing to
      11beta-OHD and provides evidence for prenatal diagnosis and genetic counseling.
      In addition, our results confirm the two novel CYP11B1 mutations led to impaired
      11-hydroxylase activity in vitro.

PMID- 28514644
TI  - The importance of hormonal circadian rhythms in daily feeding patterns: An
      illustration with simulated pigs.
AB  - The interaction between hormonal circadian rhythms and feeding behaviour is not
      well understood. This study aimed to deepen our understanding of mechanisms
      underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a
      case study. Pigs show an alternans feeding pattern, that is, a small peak of feed
      intake at the beginning of the day and a larger peak at the end of the day. We
      simulated the feeding behaviour of pigs over a 24h period. The simulation model
      contained mechanisms that regulate feeding behaviour of animals, including:
      processing of feed in the gastrointestinal tract, fluctuation in energy balance,
      circadian rhythms of melatonin and cortisol and motivational decision-making.
      From the interactions between these various processes, feeding patterns (e.g.
      feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as
      well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted
      empirical data well, indicating that our model contains relevant mechanisms. The
      circadian rhythms of cortisol and melatonin explained the alternans pattern of
      feeding in pigs. Additionally, the timing and amplitude of cortisol peaks
      affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results
      suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are
      less important in circadian regulation of feeding behaviour than previously
      thought. These results are relevant to animal species with a metabolic and
      endocrine system similar to that of pigs, such as humans. Moreover, the modelling
      approach to understand feeding behaviour can be applied to other animal species.

PMID- 28514645
TI  - Oleanolic acid modulates the renin-angiotensin system and cardiac natriuretic
      hormone concomitantly with volume and pressure balance in rats.
AB  - Oleanolic acid is known to possess beneficial effects on the regulation of the
      cardiovascular homeostasis. However, the exact nature of the role of oleanolic
      acid on the regulation of body fluid balance and blood pressure homeostasis and
      its mechanisms involved are not well defined. Experiments were performed to
      identify the effects of oleanolic acid on the renin-angiotensin system and
      cardiac natriuretic hormone (ANP) system, and also renal function and blood
      pressure in normotensive and renovascular hypertensive rats. The change in the
      plasma levels of hormones and the expressions of renin, angiotensin II receptors,
      ANP, natriuretic peptide receptor-C, M2 muscarinic receptor and GIRK4 were
      determined in the kidney, heart and aorta. Oleanolic acid was administered orally
      for 1 or 3 weeks. Here, we found that oleanolic acid suppressed plasma levels of
      renin activity and aldosterone and intrarenal levels of renin and angiotensin II
      type 1 receptor expression and increased angiotensin II type 2 receptor in
      normotensive and hypertensive rats. Also, oleanolic acid increased plasma levels
      of ANP. Further, oleanolic acid suppressed angiotensin II type 1 receptor and
      natriuretic peptide receptor-C expression and increased angiotensin II type 2
      receptor and ANP expression in the heart and aorta. Along with these changes,
      oleanolic acid accentuated urinary volume, electrolyte excretion and glomerular
      filtration rate in normotensive rats and suppressed arterial blood pressure in
      hypertensive rats. These findings suggest that beneficial effects of oleanolic
      acid on the cardiorenal system are closely associated with its roles on the renin
      angiotensin system and cardiac natriuretic hormone system.

PMID- 28514643
TI  - Yorkie regulates epidermal wound healing in Drosophila larvae independently of
      cell proliferation and apoptosis.
AB  - Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway,
      has well-characterized roles in balancing apoptosis and cell division during
      organ growth control. Yki is also required in diverse tissue regenerative
      contexts. In most cases this requirement reflects its well-characterized roles in
      balancing apoptosis and cell division. Whether Yki has repair functions outside
      of the control of cell proliferation, death, and growth is not clear. Here we
      show that Yki and Scalloped (Sd) are required for epidermal wound closure in the
      Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki
      transiently translocates to some epidermal nuclei upon wounding. Genetic analysis
      strongly suggests that Yki interacts with the known wound healing pathway, Jun N
      terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular
      Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or
      parallel to JNK signaling and does not appear to regulate either proliferation or
      apoptosis in the larval epidermis during wound repair. Analysis of actin
      structures after wounding suggests that Yki and Sd promote wound closure through
      actin regulation. In sum, we found that Yki regulates an epithelial tissue repair
      process independently of its previously documented roles in balancing
      proliferation and apoptosis.

PMID- 28514647
TI  - The importance of bioinformatics for connecting data-driven lipidomics and
      biological insights.

PMID- 28514648
TI  - Determination of fenobucarb residues in animal and aquatic food products using
      liquid chromatography-tandem mass spectrometry coupled with a QuEChERS extraction
      method.
AB  - A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction
      method coupled with liquid chromatography-electrospray ionization tandem mass
      spectrometry (LC-ESI+/MS-MS) was developed for quantification of fenobucarb
      residues in animal food products, such as porcine muscle, egg, and whole milk,
      and aquatic food products, such as eel, flatfish, and shrimp. Acetonitrile with
      the addition of 0.1% trifluoroacetic acid was employed as an extraction solvent
      and was compared with acetonitrile alone and 0.1% formic acid in acetonitrile.
      All extracted samples were purified using C18 sorbent. The best extraction
      efficiencies, expressed as recovery at two spiking levels equivalent to 1- and 2
      times the limit of quantification (LOQ=2MUg/kg) were achieved using 0.1%
      trifluoroacetic acid in acetonitrile and ranged from 61.38 to 102.21% in all
      matrices, with relative standard deviations (RSDs) < 13% (except for the low
      spiking of porcine muscle and the high spiking of whole milk, for which the RSDs
      were>20%). Six-point matrix-matched calibration was used for quantification and
      the determination coefficients were good (R2>=0.9865). The method was verified by
      application to samples purchased from local markets and none of the samples
      tested positive. In conclusion, the developed method is simple and versatile and
      can be used for the routine detection of fenobucarb in different animal food
      products having varying protein and fat contents with satisfactory accuracy and
      precision.

PMID- 28514646
TI  - Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma
      samples for accurate measurement of anti-Yellow fever virus neutralizing
      antibodies.
AB  - Technological innovations in vaccinology have recently contributed to bring about
      novel insights for the vaccine-induced immune response. While the current
      protocols that use peripheral blood samples may provide abundant data, a range of
      distinct components of whole blood samples are required and the different
      anticoagulant systems employed may impair some properties of the biological
      sample and interfere with functional assays. Although the interference of heparin
      in functional assays for viral neutralizing antibodies such as the functional
      plaque-reduction neutralization test (PRNT), considered the gold-standard method
      to assess and monitor the protective immunity induced by the Yellow fever virus
      (YFV) vaccine, has been well characterized, the development of pre-analytical
      treatments is still required for the establishment of optimized protocols. The
      present study intended to optimize and evaluate the performance of pre-analytical
      treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to
      provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The
      study was designed in three steps, including: I. Problem statement; II. Pre
      analytical steps; III. Analytical steps. Data confirmed the interference of
      heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of
      conditions for ECT pre-treatment were tested to optimize the heparin removal. The
      optimized protocol was pre-validated to determine the effectiveness of heparin
      plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The
      validation and comparative performance was carried out by using a large range of
      serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and
      17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of
      heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing
      antibodies.

PMID- 28514624
TI  - Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.
AB  - BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib
      substantially raises the high-density lipoprotein (HDL) cholesterol level,
      reduces the low-density lipoprotein (LDL) cholesterol level, and enhances
      cellular cholesterol efflux capacity. We sought to determine the effect of
      evacetrapib on major adverse cardiovascular outcomes in patients with high-risk
      vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo
      controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the
      following conditions: an acute coronary syndrome within the previous 30 to 365
      days, cerebrovascular atherosclerotic disease, peripheral vascular arterial
      disease, or diabetes mellitus with coronary artery disease. Patients were
      randomly assigned to receive either evacetrapib at a dose of 130 mg or matching
      placebo, administered daily, in addition to standard medical therapy. The primary
      efficacy end point was the first occurrence of any component of the composite of
      death from cardiovascular causes, myocardial infarction, stroke, coronary
      revascularization, or hospitalization for unstable angina. RESULTS: At 3 months,
      a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib
      versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL
      cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo.
      After 1363 of the planned 1670 primary end-point events had occurred, the data
      and safety monitoring board recommended that the trial be terminated early
      because of a lack of efficacy. After a median of 26 months of evacetrapib or
      placebo, a primary end-point event occurred in 12.9% of the patients in the
      evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01;
      95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the
      cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on
      established lipid biomarkers, treatment with evacetrapib did not result in a
      lower rate of cardiovascular events than placebo among patients with high-risk
      vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number,
      NCT01687998 .).

PMID- 28514649
TI  - Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in
      Pluripotent Stem Cells.
AB  - During mitosis, transcription is halted and many chromatin features are lost,
      posing a challenge for the continuity of cell identity, particularly in fast
      cycling stem cells, which constantly balance self-renewal with differentiation.
      Here we show that, in pluripotent stem cells, certain histone marks and stem cell
      regulators remain associated with specific genomic regions of mitotic chromatin,
      a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes
      are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4,
      while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a
      cell-type invariant manner. Temporal degradation of OCT4 during mitotic exit
      compromises its ability both to maintain and induce pluripotency, suggesting that
      its regulatory function partly depends on its bookmarking activity. Together, our
      data document a widespread yet specific bookmarking by histone modifications and
      transcription factors promoting faithful and efficient propagation of stemness
      after cell division.

PMID- 28514650
TI  - The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during
      Homologous Recombination.
AB  - The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler
      that acts in transcription, replication, and genome stability. It is required for
      resistance against genotoxic agents and is involved in the repair of DNA double
      strand breaks (DSBs) by homologous recombination (HR). However, the causes of the
      HR defect in INO80-C mutant cells are controversial. Here, we unite previous
      findings using a system to study HR with high spatial resolution in budding
      yeast. We find that INO80-C has at least two distinct functions during HR-DNA end
      resection and presynaptic filament formation. Importantly, the second function is
      linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic
      filament formation and HR are restored in INO80-C-deficient mutants, suggesting
      that presynaptic filament formation is the crucial INO80-C function during HR.

PMID- 28514651
TI  - Modeling Genomic Instability and Selection Pressure in a Mouse Model of Melanoma.
AB  - Tumor evolution is an iterative process of selection for pro-oncogenic
      aberrations. This process can be accelerated by genomic instability, but how it
      interacts with different selection bottlenecks to shape the evolving genomic
      landscape remains understudied. Here, we assessed tumor initiation and therapy
      resistance bottlenecks in mouse models of melanoma, with or without genomic
      instability. At the initiation bottleneck, whole-exome sequencing revealed that
      drug-naive tumors were genomically silent, and this was surprisingly unaffected
      when genomic instability was introduced via telomerase inactivation. We
      hypothesize that the strong engineered alleles created low selection pressure. At
      the therapy resistance bottleneck, strong selective pressure was applied using a
      BRAF inhibitor. In the absence of genomic instability, tumors acquired a non
      genomic drug resistance mechanism. By contrast, telomerase-deficient, drug
      resistant melanomas acquired highly recurrent copy number gains. These proof-of
      principle experiments demonstrate how different selection pressures can interact
      with genomic instability to impact tumor evolution.

PMID- 28514654
TI  - Crystal Structure of Tetrameric Arabidopsis MYC2 Reveals the Mechanism of
      Enhanced Interaction with DNA.
AB  - Jasmonates (JAs) are essential plant hormones that play important roles in the
      regulation of plant growth and the response to environmental stress. In the JA
      signaling pathway, the core transcription factors are a class of basic helix-loop
      helix (bHLH) proteins, including MYC2, MYC3, and MYC4, that have different
      regulatory capacities. Here, we report the 2.7 A crystal structure of the MYC2
      bHLH domain complexed with G-box DNA, showing a cis-tetrameric structure.
      Biochemical assays confirmed that full-length MYC2 forms a stable homo-tetramer
      both in solution and in DNA-bound states, whereas MYC3 forms only a homodimer.
      Isothermal titration calorimetry (ITC) assays demonstrated that tetramerization
      enhanced DNA binding affinity, and fluorescence resonance energy transfer (FRET)
      assay indicated DNA looping potential of tetrameric MYC2. Luciferase assay
      further confirmed the importance of tetramerization in transcriptional
      regulation. Our studies provide a mechanistic explanation for the regulatory
      differences of MYC transcription factors.

PMID- 28514652
TI  - Thymidine Catabolism as a Metabolic Strategy for Cancer Survival.
AB  - Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism,
      plays a pivotal role in tumor progression; however, the mechanisms underlying
      this role are not fully understood. Here, we found that TP-mediated thymidine
      catabolism could supply the carbon source in the glycolytic pathway and thus
      contribute to cell survival under conditions of nutrient deprivation. In TP
      expressing cells, thymidine was converted to metabolites, including glucose 6
      phosphate, lactate, 5-phospho-alpha-D-ribose 1-diphosphate, and serine, via the
      glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites
      were required for the survival of cells under low-glucose conditions.
      Furthermore, activation of thymidine catabolism was observed in human gastric
      cancer. These findings demonstrate that thymidine can serve as a glycolytic
      pathway substrate in human cancer cells.

PMID- 28514653
TI  - The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage
      Populations and Mediates Pancreatic Tumorigenesis.
AB  - The contributions of the innate immune system to the development of pancreatic
      cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of
      pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia
      [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN)
      when oncogenic KRas is present. However, it remains unclear when and how this
      inflammatory macrophage population is replaced by tumor-promoting macrophages.
      Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert
      inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions.
      We further show that Ym1+ macrophages release factors, such as IL-1ra and CCL2,
      to drive pancreatic fibrogenesis and tumorigenesis. Treatment of mice expressing
      oncogenic KRas under an acinar cell-specific promoter with a neutralizing
      antibody for IL-13 significantly decreased the accumulation of alternatively
      activated macrophages at these lesions, resulting in decreased fibrosis and
      lesion growth.

PMID- 28514655
TI  - Inhibitory Control of Feature Selectivity in an Object Motion Sensitive Circuit
      of the Retina.
AB  - Object motion sensitive (OMS) W3-retinal ganglion cells (W3-RGCs) in mice respond
      to local movements in a visual scene but remain silent during self-generated
      global image motion. The excitatory inputs that drive responses of W3-RGCs to
      local motion were recently characterized, but which inhibitory neurons suppress
      W3-RGCs' responses to global motion, how these neurons encode motion information,
      and how their connections are organized along the excitatory circuit axis remains
      unknown. Here, we find that a genetically identified amacrine cell (AC) type, TH2
      AC, exhibits fast responses to global motion and slow responses to local motion.
      Optogenetic stimulation shows that TH2-ACs provide strong GABAA receptor-mediated
      input to W3-RGCs but only weak input to upstream excitatory neurons. Cell-type
      specific silencing reveals that temporally coded inhibition from TH2-ACs cancels
      W3-RGC spike responses to global but not local motion stimuli and, thus, controls
      the feature selectivity of OMS signals sent to the brain.

PMID- 28514656
TI  - Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter
      Cells.
AB  - Mammalian cells have two fundamentally different states, proliferative and
      quiescent, but our understanding of how and why cells switch between these states
      is limited. We previously showed that actively proliferating populations contain
      a subpopulation that enters quiescence (G0) in an apparently stochastic manner.
      Using single-cell time-lapse imaging of CDK2 activity and DNA damage, we now show
      that unresolved endogenous replication stress in the previous (mother) cell cycle
      prompts p21-dependent entry of daughter cells into quiescence immediately after
      mitosis. Furthermore, the amount of time daughter cells spend in quiescence is
      correlated with the extent of inherited damage. Our study thus links replication
      errors in one cell cycle to the fate of daughter cells in the subsequent cell
      cycle. More broadly, this work reveals that entry into quiescence is not purely
      stochastic but has a strong deterministic component arising from a memory of
      events that occurred in the previous generation(s).

PMID- 28514658
TI  - CNS Macrophages Control Neurovascular Development via CD95L.
AB  - The development of neurons and vessels shares striking anatomical and molecular
      features, and it is presumably orchestrated by an overlapping repertoire of
      extracellular signals. CNS macrophages have been implicated in various
      developmental functions, including the morphogenesis of neurons and vessels.
      However, whether CNS macrophages can coordinately influence neurovascular
      development and the identity of the signals involved therein is unclear. Here, we
      demonstrate that activity of the cell surface receptor CD95 regulates neuronal
      and vascular morphogenesis in the post-natal brain and retina. Furthermore, we
      identify CNS macrophages as the main source of CD95L, and macrophage-specific
      deletion thereof reduces both neurovascular complexity and synaptic activity in
      the brain. CD95L-induced neuronal and vascular growth is mediated through src
      family kinase (SFK) and PI3K signaling. Together, our study highlights a
      coordinated neurovascular development instructed by CNS macrophage-derived CD95L,
      and it underlines the importance of macrophages for the establishment of the
      neurovascular network during CNS development.

PMID- 28514657
TI  - Huntington's Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal
      WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits.
AB  - Brain microvascular endothelial cells (BMECs) are an essential component of the
      blood-brain barrier (BBB) that shields the brain against toxins and immune cells.
      While BBB dysfunction exists in neurological disorders, including Huntington's
      disease (HD), it is not known if BMECs themselves are functionally compromised to
      promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction
      remain elusive given limitations with mouse models and post-mortem tissue to
      identify primary deficits. We undertook a transcriptome and functional analysis
      of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD
      patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic
      abnormalities in angiogenesis and barrier properties, as well as in signaling
      pathways governing these processes. Thus, our findings provide an iPSC-derived
      BBB model for a neurodegenerative disease and demonstrate autonomous
      neurovascular deficits that may underlie HD pathology with implications for
      therapeutics and drug delivery.

PMID- 28514661
TI  - Innate Recognition of Intracellular Bacterial Growth Is Driven by the TIFA
      Dependent Cytosolic Surveillance Pathway.
AB  - Intestinal epithelial cells (IECs) act as sentinels for incoming pathogens.
      Cytosol-invasive bacteria, such as Shigella flexneri, trigger a robust pro
      inflammatory nuclear factor kappaB (NF-kappaB) response from IECs that is
      believed to depend entirely on the peptidoglycan sensor NOD1. We found that,
      during Shigella infection, the TRAF-interacting forkhead-associated protein A
      (TIFA)-dependent cytosolic surveillance pathway, which senses the bacterial
      metabolite heptose-1,7-bisphosphate (HBP), functions after NOD1 to detect
      bacteria replicating free in the host cytosol. Whereas NOD1 mediated a transient
      burst of NF-kappaB activation during bacterial entry, TIFA sensed HBP released
      during bacterial replication, assembling into large signaling complexes to drive
      a dynamic inflammatory response that reflected the rate of intracellular
      bacterial proliferation. Strikingly, IECs lacking TIFA were unable to
      discriminate between proliferating and stagnant intracellular bacteria, despite
      the NOD1/2 pathways being intact. Our results define TIFA as a rheostat for
      intracellular bacterial replication, escalating the immune response to invasive
      Gram-negative bacteria that exploit the host cytosol for growth.

PMID- 28514659
TI  - The Intergenic Recombinant HLA-B*46:01 Has a Distinctive Peptidome that Includes
      KIR2DL3 Ligands.
AB  - HLA-B*46:01 was formed by an intergenic mini-conversion, between HLA-B*15:01 and
      HLA-C*01:02, in Southeast Asia during the last 50,000 years, and it has since
      become the most common HLA-B allele in the region. A functional effect of the
      mini-conversion was introduction of the C1 epitope into HLA-B*46:01, making it an
      exceptional HLA-B allotype that is recognized by the C1-specific natural killer
      (NK) cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA
      B*46:01 has a low-diversity peptidome that is distinct from those of its parents.
      A minority (21%) of HLA-B*46:01 peptides, with common C-terminal characteristics,
      form ligands for KIR2DL3. The HLA-B*46:01 peptidome is predicted to be enriched
      for peptide antigens derived from Mycobacterium leprae. Overall, the results
      indicate that the distinctive peptidome and functions of HLA-B*46:01 provide
      carriers with resistance to leprosy, which drove its rapid rise in frequency in
      Southeast Asia.

PMID- 28514660
TI  - Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers
      Premature Inclusion Membrane Lysis and Host Cell Death.
AB  - Chlamydia trachomatis is a human pathogen associated with significant morbidity
      worldwide. As obligate intracellular parasites, chlamydiae must survive within
      eukaryotic cells for sufficient time to complete their developmental cycle. To
      promote host cell survival, chlamydiae express poorly understood anti-apoptotic
      factors. Using recently developed genetic tools, we show that three inclusion
      membrane proteins (Incs) out of eleven examined are required for inclusion
      membrane stability and avoidance of host cell death pathways. In the absence of
      specific Incs, premature inclusion lysis results in recognition by
      autophagolysosomes, activation of intrinsic apoptosis, and premature termination
      of the chlamydial developmental cycle. Inhibition of autophagy or knockdown of
      STING prevented host cell death and activation of intrinsic apoptosis.
      Significantly, these findings emphasize the importance of Incs in the
      establishment of a replicative compartment that sequesters the pathogen from host
      surveillance systems.

PMID- 28514662
TI  - A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell
      Population Characterized by Group 1 Properties.
AB  - The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes,
      such as epidermal Vgamma3 T cells, intestinal intraepithelial CD8alphaalpha+ T
      lymphocytes, and CD49a+ liver natural killer (NK) cells. As the latter have
      recently been shown to be distinct from conventional NK cells and have innate
      lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on
      intestinal ILC populations. Here, we show that Ly49E expression is very low on
      known ILC populations, but it can be used to define a previously unrecognized
      intraepithelial innate lymphoid population. This Ly49E-positive population is
      negative for NKp46 and CD8alphaalpha, expresses CD49a and CD103, and requires T
      bet expression and IL-15 signaling for differentiation and/or survival.
      Transcriptome analysis reveals a group 1 ILC gene profile, different from NK
      cells, iCD8alpha cells, and intraepithelial ILC1. Importantly, NKp46
      CD8alphaalpha-Ly49E+ cells produce interferon (IFN)-gamma, suggesting that this
      previously unrecognized population may contribute to Th1-mediated immunity.

PMID- 28514663
TI  - Fatty Acid Oxidation in Zebrafish Adipose Tissue Is Promoted by 1alpha,25(OH)2D3.
AB  - 1alpha,25(OH)2D3 (vitamin D3) is crucial for mineral homeostasis in mammals, but
      the precise effects of 1alpha,25(OH)2D3 in adipose tissue remain to be clarified
      in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome
      P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological
      function(s) of 1alpha,25(OH)2D3 in teleosts, we generated two independent cyp2r1
      deficient zebrafish lines. These mutants exhibit retarded growth and increased
      obesity, especially in the visceral adipose tissue (VAT). These defects could be
      rescued with 25(OH)D3 treatments. ChIP-PCR analyses demonstrated that pgc1a is
      the target of the vitamin D receptor in the liver and VAT of zebrafish.
      Significantly decreased protein levels of Pgc1a, impaired mitochondrial
      biogenesis, and free fatty acid oxidation are also observed in the cyp2r1 mutant
      VAT. Our results demonstrate that regulation of 1alpha,25(OH)2D3 during lipid
      metabolism occurs through the regulation of Pgc1a for mitochondrial biogenesis
      and oxidative metabolism within zebrafish VAT.

PMID- 28514665
TI  - Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of
      Antibody Repertoires throughout B Cell Development.
AB  - Antibody repertoire diversity and plasticity is crucial for broad protective
      immunity. Repertoires change in size and diversity across multiple B cell
      developmental stages and in response to antigen exposure. However, we still lack
      fundamental quantitative understanding of the extent to which repertoire
      diversity is predetermined. Therefore, we implemented a systems immunology
      framework for quantifying repertoire predetermination on three distinct levels:
      (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen
      exposure (three structurally different proteins), and (3) four antibody
      repertoire components (V-gene usage, clonal expansion, clonal diversity,
      repertoire size) extracted from antibody repertoire sequencing data (400 million
      reads). Across all three levels, we detected a dynamic balance of high genetic
      (e.g., >90% for V-gene usage and clonal expansion in naive B cells) and antigen
      driven (e.g., 40% for clonal diversity in plasma cells) predetermination and
      stochastic variation. Our study has implications for the prediction and
      manipulation of humoral immunity.

PMID- 28514664
TI  - Lack of MTTP Activity in Pluripotent Stem Cell-Derived Hepatocytes and
      Cardiomyocytes Abolishes apoB Secretion and Increases Cell Stress.
AB  - Abetalipoproteinemia (ABL) is an inherited disorder of lipoprotein metabolism
      resulting from mutations in microsomal triglyceride transfer protein (MTTP). In
      addition to expression in the liver and intestine, MTTP is expressed in
      cardiomyocytes, and cardiomyopathy has been reported in several ABL cases. Using
      induced pluripotent stem cells (iPSCs) generated from an ABL patient homozygous
      for a missense mutation (MTTPR46G), we show that human hepatocytes and
      cardiomyocytes exhibit defects associated with ABL disease, including loss of
      apolipoprotein B (apoB) secretion and intracellular accumulation of lipids.
      MTTPR46G iPSC-derived cardiomyocytes failed to secrete apoB, accumulated
      intracellular lipids, and displayed increased cell death, suggesting intrinsic
      defects in lipid metabolism due to loss of MTTP function. Importantly, these
      phenotypes were reversed after the correction of the MTTPR46G mutation by
      CRISPR/Cas9 gene editing. Together, these data reveal clear cellular defects in
      iPSC-derived hepatocytes and cardiomyocytes lacking MTTP activity, including a
      cardiomyocyte-specific regulated stress response to elevated lipids.

PMID- 28514667
TI  - A Design Principle for an Autonomous Post-translational Pattern Formation.

PMID- 28514668
TI  - Concurrent white matter bundles and grey matter networks using independent
      component analysis.
AB  - Developments in non-invasive diffusion MRI tractography techniques have permitted
      the investigation of both the anatomy of white matter pathways connecting grey
      matter regions and their structural integrity. In parallel, there has been an
      expansion in automated techniques aimed at parcellating grey matter into distinct
      regions based on functional imaging. Here we apply independent component analysis
      to whole-brain tractography data to automatically extract brain networks based on
      their associated white matter pathways. This method decomposes the tractography
      data into components that consist of paired grey matter 'nodes' and white matter
      'edges', and automatically separates major white matter bundles, including known
      cortico-cortical and cortico-subcortical tracts. We show how this framework can
      be used to investigate individual variations in brain networks (in terms of both
      nodes and edges) as well as their associations with individual differences in
      behaviour and anatomy. Finally, we investigate correspondences between
      tractography-based brain components and several canonical resting-state networks
      derived from functional MRI.

PMID- 28514669
TI  - The relationship between cognition and depressive symptoms, and factors modifying
      this association, in Alzheimer's disease: A multivariate multilevel model.
AB  - OBJECTIVES: To examine whether there was a bidirectional association between
      cognition and depressive symptoms in Alzheimer's disease (AD), and to explore the
      role of socio-demographic factors and daily performance in this association.
      METHODS: We conducted a longitudinal study of 104 community-dwelling patients
      with confirmed AD from Taiyuan, China. We assessed cognition and depressive
      symptoms (dependent variables) with the Montreal Cognitive Assessment (MoCA) and
      the Geriatric Depression Scale-30 (GDS-30), respectively. Socio-demographic
      information and daily performance were treated as explanatory variables. A
      multivariate multilevel model was built to investigate the interrelationship
      between patients' cognition and depression, as well as the effect of related
      factors on both outcomes. RESULTS: MoCA scores were negatively correlated with
      GDS-30 both at the subject level (correlation coefficient r3=-0.68, chi2=19.26,
      P<0.001) and time point level (r2=-0.35, chi2=35.68, P<0.001) in patients with
      AD. Multivariate analysis showed several significant factors for cognitive
      function, including educational level, personality, hobbies, exercise, reading,
      aluminum utensil use, dietary restriction and hypertension (regression
      coefficients: 0.60, 0.52, 0.51, 0.48, 0.45, -0.48, 0.67, and -0.74,
      respectively). Significant factors for depressive symptoms included family
      status, employment before retirement, homemaking, reading, aluminum utensil use,
      dietary restriction, and hypertension (regression coefficients: 3.09, -1.33, 
      1.62, -1.31, 0.96, -1.15, and 1.14, respectively). CONCLUSION: These findings
      indicated that cognition was negatively associated with depression in patients
      with AD, and both were influenced by reading, aluminum utensil use, dietary
      restriction, and hypertension. Considering patient factors may help to slow the
      progression of dementia.

PMID- 28514666
TI  - A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells.
AB  - Epstein-Barr virus (EBV) replication contributes to multiple human diseases,
      including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas,
      and oral hairy leukoplakia. We performed systematic quantitative analyses of
      temporal changes in host and EBV proteins during lytic replication to gain
      insights into virus-host interactions, using conditional Burkitt lymphoma models
      of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69
      EBV proteins, including >500 plasma membrane proteins, providing temporal views
      of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced
      remodeling of cell cycle, innate and adaptive immune pathways, including
      upregulation of the complement cascade and proteasomal degradation of the B cell
      receptor complex, conserved between EBV types I and II. Cross-comparison with
      proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma
      associated herpesvirus immunoevasin identified host factors targeted by multiple
      herpesviruses. Our results provide an important resource for studies of EBV
      replication.

PMID- 28514671
TI  - Evaluation of improved IS6110 LAMP assay for diagnosis of pulmonary and extra
      pulmonary tuberculosis.
AB  - In the present study, IS6110 loop mediated isothermal amplification (LAMP) assay
      was modified using dUTP-UNG (uracil-DNA N-glycosylase) strategy to prevent
      carryover contamination, and was evaluated using clinical specimens. The clinical
      specimens were collected from 236 suspected patients of pulmonary tuberculosis
      and 315 specimens of suspected patients of extra pulmonary tuberculosis. DNA was
      extracted from specimens and used as template for nucleic acid amplification. The
      results were evaluated with culture method as gold standard. Modified IS6110 LAMP
      assay showed high sensitivity (94.4%) and specificity (97.2%) in specimens
      collected from suspected pulmonary tuberculosis patients. Sensitivity was
      comparatively less (86.67%) in extra pulmonary specimens while specificity was
      94.04%. In conclusion, IS6110 LAMP assay was modified to prevent carry over
      contamination and it was validated to be rapid, sensitive and specific method
      with prospective application in resource-limited settings.

PMID- 28514670
TI  - Radiation Safety in Children With Congenital and Acquired Heart Disease: A
      Scientific Position Statement on Multimodality Dose Optimization From the Image
      Gently Alliance.
AB  - There is a need for consensus recommendations for ionizing radiation dose
      optimization during multimodality medical imaging in children with congenital and
      acquired heart disease (CAHD). These children often have complex diseases and may
      be exposed to a relatively high cumulative burden of ionizing radiation from
      medical imaging procedures, including cardiac computed tomography, nuclear
      cardiology studies, and fluoroscopically guided diagnostic and interventional
      catheterization and electrophysiology procedures. Although these imaging
      procedures are all essential to the care of children with CAHD and have
      contributed to meaningfully improved outcomes in these patients, exposure to
      ionizing radiation is associated with potential risks, including an increased
      lifetime attributable risk of cancer. The goal of these recommendations is to
      encourage informed imaging to achieve appropriate study quality at the lowest
      achievable dose. Other strategies to improve care include a patient-centered
      approach to imaging, emphasizing education and informed decision making and
      programmatic approaches to ensure appropriate dose monitoring. Looking ahead,
      there is a need for standardization of dose metrics across imaging modalities, so
      as to encourage comparative effectiveness studies across the spectrum of CAHD in
      children.

PMID- 28514672
TI  - Biochemical Underpinnings of Immune Cell Metabolic Phenotypes.
AB  - The metabolism of immune cells affects their function and influences host
      immunity. This review explores how immune cell metabolic phenotypes reflect
      biochemical dependencies and highlights evidence that both the metabolic state of
      immune cells and nutrient availability can alter immune responses. The central
      importance of oxygen, energetics, and redox homeostasis in immune cell
      metabolism, and how these factors are reflected in different metabolic
      phenotypes, is also discussed. Linking immune cell metabolic phenotype to
      effector functions is important to understand how altering metabolism can impact
      the way in which immune cells meet their metabolic demands and affect the immune
      response in various disease contexts.

PMID- 28514676
TI  - Human ILC1: To Be or Not to Be.

PMID- 28514674
TI  - MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue
      Resident Immune Cells.
AB  - Tissue-resident immune cells must balance survival in peripheral tissues with the
      capacity to respond rapidly upon infection or tissue damage, and in turn couple
      these responses with intrinsic metabolic control and conditions in the tissue
      microenvironment. The serine/threonine kinase mammalian/mechanistic target of
      rapamycin (mTOR) is a central integrator of extracellular and intracellular
      growth signals and cellular metabolism and plays important roles in both innate
      and adaptive immune responses. This review discusses the function of mTOR
      signaling in the differentiation and function of tissue-resident immune cells,
      with focus on the role of mTOR as a metabolic sensor and its impact on metabolic
      regulation in innate and adaptive immune cells. We also discuss the impact of
      metabolic constraints in tissues on immune homeostasis and disease, and how
      manipulating mTOR activity with drugs such as rapamycin can modulate immunity in
      these contexts.

PMID- 28514677
TI  - Human Group 1 Innate Lymphocytes Are Negative for Surface CD3epsilon but Express
      CD5.

PMID- 28514673
TI  - Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity.
AB  - Recognition of pathogens by innate and adaptive immune cells instructs rapid
      alterations of cellular processes to promote effective resolution of infection.
      To accommodate increased bioenergetic and biosynthetic demands, metabolic
      pathways are harnessed to maximize proliferation and effector molecule
      production. In parallel, activation initiates context-specific gene-expression
      programs that drive effector functions and cell fates that correlate with changes
      in epigenetic landscapes. Many chromatin- and DNA-modifying enzymes make use of
      substrates and cofactors that are intermediates of metabolic pathways, providing
      potential cross talk between metabolism and epigenetic regulation of gene
      expression. In this review, we discuss recent studies of T cells and macrophages
      supporting a role for metabolic activity in integrating environmental signals
      with activation-induced gene-expression programs through modulation of the
      epigenome and speculate as to how this may influence context-specific macrophage
      and T cell responses to infection.

PMID- 28514678
TI  - Toward Meaningful Definitions of Innate-Lymphoid-Cell Subsets.

PMID- 28514679
TI  - Size Doesn't Matter: Shorter Antibody Loops Can Infiltrate HIV's Env Apex
      Defenses.
AB  - An HIV vaccine that elicits broadly neutralizing antibodies, which often have
      unusual structural features, has not yet been developed. In Immunity this month,
      Cale et al., 2017 describe how a new mode of binding allows a conventional
      antibody to infiltrate HIV's armor.

PMID- 28514675
TI  - Metabolic Regulation of the Immune Humoral Response.
AB  - Productive humoral responses require that naive B cells and their differentiated
      progeny move among distinct micro-environments. In this review, we discuss how
      studies are beginning to address the nature of these niches as well as the
      interplay between cellular signaling, metabolic programming, and adaptation to
      the locale. Recent work adds evidence to the expectation that B cells at distinct
      stages of development or functional subsets are influenced by the altered
      profiles of nutrients and metabolic by-products that distinguish these sites.
      Moreover, emerging findings reveal a cross-talk among the external milieu, signal
      transduction pathways, and transcription factors that direct B cell fate in the
      periphery.

PMID- 28514680
TI  - Understanding Spontaneous Conversion: The Case of the Ly6C- Monocyte.
AB  - Mouse blood monocytes include two main subsets usually discriminated by the
      expression of the Ly6C surface marker. The study by Mildner et al. (2017) in this
      issue of Immunity clarifies the transcriptional circuits controlling the
      generation of Ly6C- cells from their obligate precursors, the Ly6C+ monocytes.

PMID- 28514681
TI  - Only Two Can Tango: Mast Cells Displace Epithelial Cells to Dance with ILC2s.
AB  - Mast cells have been implicated in protective immunity to helminth infection, but
      the precise mechanism remains unclear. In this issue of Immunity, Shimokawa et
      al., 2017 report that mast cells are a bridge linking dying epithelial cells with
      effector type 2 innate lymphoid cells.

PMID- 28514682
TI  - You Can Breathe Easy: IFNlambda Handles Flu without Triggering a Damaging
      Inflammatory Response.
AB  - Type III interferon (IFNlambda) and type I IFN (IFNalpha/beta) have overlapping
      antiviral activities in the lung. In this issue of Immunity, Galani et al. (2017)
      identify a critical early role for IFNlambda, not shared by IFNalpha/beta, in
      protection of the lung following influenza virus infection.

PMID- 28514683
TI  - Dengue Antibodies, then Zika: A Fatal Sequence in Mice.
AB  - Anti-Dengue virus (DENV) antibodies can be either protective or pathogenic in
      humans with prior DENV infection. In a recent issue of Science, Bardina et al.
      (2017) demonstrated that passive transfer of immune plasma against DENV and West
      Nile virus (WNV) can enhance Zika virus (ZIKV) infection and pathogenesis in
      mice.

PMID- 28514684
TI  - CD4+ T Cell Activation and Vascular Normalization: Two Sides of the Same Coin?
AB  - Normalization of tumor blood vessels enhances the infiltration and functions of T
      cells. Tian et al. (2017) report that effector CD4+ T cells, in turn, support
      vascular normalization, highlighting intertwined roles for blood vessels and T
      cells in cancer.

PMID- 28514686
TI  - Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural
      Determination of a Stabilized Subtype C HIV Envelope Glycoprotein.
AB  - Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers
      and high-resolution clade A, B, and G structures and elicit neutralizing
      antibodies. However, a high-resolution clade C structure is critical, as this
      subtype accounts for the majority of HIV infections worldwide, but well-ordered
      clade C Env trimers are more challenging to produce due to their instability.
      Based on targeted glycine substitutions in the Env fusion machinery, we defined a
      general approach that disfavors helical transitions leading to post-fusion
      conformations, thereby favoring the pre-fusion state. We generated a stabilized,
      soluble clade C Env (16055 NFL) and determined its crystal structure at 3.9 A.
      Its overall conformation is similar to SOSIP.664 and native Env trimers but
      includes a covalent linker between gp120 and gp41, an engineered 201-433
      disulfide bond, and density corresponding to 22 N-glycans. Env-structure-guided
      design strategies resulted in multiple homogeneous cross-clade immunogens with
      the potential to advance HIV vaccine development.

PMID- 28514685
TI  - Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that
      Lacks a Protruding Loop.
AB  - Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual
      characteristics that complicate their elicitation. Neutralizing antibodies that
      target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long
      protruding loops, which enable them to penetrate the HIV-1 glycan shield. As
      antibodies with loops of requisite length are created through uncommon
      recombination events, an alternative mode of apex binding has been sought. Here,
      we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01
      11, by using virus-like particles and conformationally stabilized Env trimers as
      B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2
      revealed a binding mode involving side-chain-to-side-chain interactions that
      reduced the distance the antibody loop must traverse the glycan shield, thereby
      facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus
      identifies a solution for V1V2-apex binding that provides a more conventional B
      cell pathway for vaccine design.

PMID- 28514687
TI  - Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing
      Antibodies that Display a Unique V2 Cap Approach.
AB  - The development of soluble envelope glycoprotein (Env) mimetics displaying
      ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The
      recently reported native, flexibly linked (NFL) design allows the generation of
      native-like trimers from clinical isolates at high yields and homogeneity. As the
      majority of infections world-wide are of the clade C subtype, we examined
      responses in non-human primates to well-ordered subtype C 16055 trimers
      administered in soluble or high-density liposomal formats. We detected superior
      germinal center formation and enhanced autologous neutralizing antibodies against
      the neutralization-resistant (tier 2) 16055 virus following inoculation of
      liposome-arrayed trimers. Epitope mapping of the neutralizing monoclonal
      antibodies (mAbs) indicated major contacts with the V2 apex, and 3D electron
      microscopy reconstructions of Fab-trimer complexes revealed a horizontal binding
      angle to the Env spike. These vaccine-elicited mAbs target the V2 cap,
      demonstrating a means to accomplish tier 2 virus neutralization by penetrating
      the dense N-glycan shield.

PMID- 28514689
TI  - Identification of a Human Clonogenic Progenitor with Strict Monocyte
      Differentiation Potential: A Counterpart of Mouse cMoPs.
AB  - Monocytes give rise to macrophages and dendritic cells (DCs) under steady-state
      and inflammatory conditions, thereby contributing to host defense and tissue
      pathology. A common monocyte progenitor (cMoP) that is strictly committed to the
      monocyte lineage has been recently identified in mice. Here, we identified human
      cMoPs as a CLEC12AhiCD64hi subpopulation of conventional granulocyte-monocyte
      progenitors (cGMPs) in umbilical cord blood and in bone marrow. Human cMoPs gave
      rise to monocyte subsets without showing any potential for differentiating into
      myeloid or lymphoid cells. Within the cGMP population, we also identified revised
      GMPs that completely lacked DC and lymphoid potential. Collectively, our findings
      expand and revise the current understanding of human myeloid cell differentiation
      pathways.

PMID- 28514688
TI  - The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses
      Thymic Innate Lymphoid Cell Development.
AB  - Innate and adaptive lymphoid development is orchestrated by the activities of E
      proteins and their antagonist Id proteins, but how these factors regulate early T
      cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear.
      Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB
      acted in synergy in the thymus to establish T cell identity and to suppress the
      aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like
      cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription
      signature by activating the expression of genes associated with Notch receptors,
      T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in
      ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire,
      including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On
      the basis of these and previous observations, we propose that the E-Id protein
      axis specifies innate and adaptive lymphoid cell fate.

PMID- 28514690
TI  - Genomic Characterization of Murine Monocytes Reveals C/EBPbeta Transcription
      Factor Dependence of Ly6C- Cells.
AB  - Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and
      man comprise two main subpopulations. Murine Ly6C+ monocytes display
      developmental plasticity and are recruited to complement tissue-resident
      macrophages and dendritic cells on demand. Murine vascular Ly6C- monocytes patrol
      the endothelium, act as scavengers, and support vessel wall repair. Here we
      characterized population and single cell transcriptomes, as well as enhancer and
      promoter landscapes of the murine monocyte compartment. Single cell RNA-seq and
      transplantation experiments confirmed homeostatic default differentiation of
      Ly6C+ into Ly6C- monocytes. The main two subsets were homogeneous, but linked by
      a more heterogeneous differentiation intermediate. We show that monocyte
      differentiation occurred through de novo enhancer establishment and activation of
      pre-established (poised) enhancers. Generation of Ly6C- monocytes involved
      induction of the transcription factor C/EBPbeta and C/EBPbeta-deficient mice
      lacked Ly6C- monocytes. Mechanistically, C/EBPbeta bound the Nr4a1 promoter and
      controlled expression of this established monocyte survival factor.

PMID- 28514691
TI  - Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and
      Clearance of Helminth Infections.
AB  - Mast cells are important for eradication of intestinal nematodes; however, their
      precise mechanisms of action have remained elusive, especially in the early phase
      of infection. We found that Spi-B-deficient mice had increased numbers of mast
      cells and rapidly expelled the Heligmosomoides polygyrus (Hp) nematode. This was
      accompanied by induction of interleukin-13 (IL-13)-producing group 2 innate
      lymphoid cells (ILC2) and goblet cell hyperplasia. Immediately after Hp
      infection, mast cells were rapidly activated to produce IL-33 in response to ATP
      released from apoptotic intestinal epithelial cells. In vivo inhibition of the
      P2X7 ATP receptor rendered the Spi-B-deficient mice susceptible to Hp,
      concomitant with elimination of mast cell activation and IL-13-producing ILC2
      induction. These results uncover a previously unknown role for mast cells in
      innate immunity in that activation of mast cells by ATP orchestrates the
      development of a protective type 2 immune response, in part by producing IL-33,
      which contributes to ILC2 activation.

PMID- 28514692
TI  - Interferon-lambda Mediates Non-redundant Front-Line Antiviral Protection against
      Influenza Virus Infection without Compromising Host Fitness.
AB  - Lambda interferons (IFNlambdas) or type III IFNs share homology, expression
      patterns, signaling cascades, and antiviral functions with type I IFNs. This has
      complicated the unwinding of their unique non-redundant roles. Through the
      systematic study of influenza virus infection in mice, we herein show that
      IFNlambdas are the first IFNs produced that act at the epithelial barrier to
      suppress initial viral spread without activating inflammation. If infection
      progresses, type I IFNs come into play to enhance viral resistance and induce pro
      inflammatory responses essential for confronting infection but causing
      immunopathology. Central to this are neutrophils which respond to both cytokines
      to upregulate antimicrobial functions but exhibit pro-inflammatory activation
      only to type I IFNs. Accordingly, Ifnlr1-/- mice display enhanced type I IFN
      production, neutrophilia, lung injury, and lethality, while therapeutic
      administration of PEG-IFNlambda potently suppresses these effects. IFNlambdas
      therefore constitute the front line of antiviral defense in the lung without
      compromising host fitness.

PMID- 28514693
TI  - Drinking despite health problems among individuals with liver disease across the
      United States.
AB  - BACKGROUND: Heavy drinking is harmful for individuals with liver disease.
      However, some of these individuals drink despite knowledge of the risks. The
      current study aims to identify factors underlying drinking despite health
      problems among individuals with liver disease. METHODS: The current study
      utilizes a subsample of individuals reporting past-year liver disease and at
      least one drink in the past year (n=331), taken from the National Epidemiologic
      Survey on Alcohol and Related Conditions-III (NESARC-III), a large nationally
      representative survey of the United States. Participants reported on drinking
      despite health problems, symptoms of psychopathology, and family history of
      alcohol problems in a cross-sectional survey. RESULTS: Drug use disorders
      (Adjusted Odds Ratio [AOR]=2.68), as well as borderline, antisocial, and
      schizotypal personality disorders (AORs=2.50-4.10), were associated with
      increased likelihood of drinking despite health problems among individuals with
      liver disease, all ps<0.05. Any anxiety disorder trended toward significance
      (AOR=2.22), p=0.06, but major depressive disorder was not associated with
      increased risk, (AOR=0.99), ps=0.97. Individuals with a family history of alcohol
      problems were also more likely to drink despite health problems (AOR=2.79),
      p<0.05. CONCLUSIONS: Several types of psychopathology, as well as a family
      history of alcohol problems, increased the likelihood of drinking despite health
      problems among individuals with liver disease. These findings highlight the need
      to intervene with heavily drinking individuals with liver disease, who may be
      drinking due to familial risk and/or comorbid psychopathology.

PMID- 28514694
TI  - The association of prenatal cocaine exposure, externalizing behavior and
      adolescent substance use.
AB  - Prenatal cocaine exposure (PCE) may increase adolescent substance use through
      alterations of neurotransmitter systems affecting fetal brain development. The
      relationship between PCE and substance use at 15 and 17 years was examined.
      Subjects (365: 186 PCE; 179 non-cocaine exposed (NCE)) supplied biologic and self
      report data using the Youth Risk Behavior Surveillance System (YRBSS) and
      Computerized Diagnostic Interview Schedule for Children (C-DISC 4) at ages 15 and
      17. The relationship between PCE and substance use was assessed using General
      Estimating Equation (GEE) analyses controlling for confounding factors including
      violence exposure and preschool lead level. Teens with PCE vs. NCE teens were 2
      times more likely to use tobacco (OR=2.1; 95% CI 1.21-3.63; p<.001) and marijuana
      (OR=1.85; CI 1.18-2.91; p<.001) and have a substance use disorder at age 17
      (OR=2.51; CI 1.00-6.28; p<.05). Evaluation of PCE status by gender revealed an
      association between PCE and marijuana use that was more pronounced for boys than
      girls at 17 years. Violence exposure was also a significant predictor of alcohol
      (p<.001), tobacco (p<.05), and marijuana (p<.0006) use and substance
      abuse/dependence (p<.01). Externalizing behavior at age 12 fully mediated the
      effects of PCE on substance use disorder at age 17 and partially mediated effects
      of PCE on tobacco use, but did not mediate effects on marijuana use. The
      percentage of substance use reported increased between 15 and 17 years, with no
      differences between the PCE and NCE groups. Data suggest specialized drug use
      prevention measures for children with PCE may benefit this high risk group.

PMID- 28514695
TI  - New product trial, use of edibles, and unexpected highs among marijuana and
      hashish users in Colorado.
AB  - OBJECTIVE: This study examines the relationships between trial of new marijuana
      or hashish products and unexpected highs, and use of edible products and
      unexpected highs. METHODS: We conducted an online survey of 634 adult, past-year
      marijuana users in Colorado. We used logistic regression models to examine the
      relationship between new product trial or edible use and unexpected highs.
      RESULTS: In the first year that recreational marijuana was legal in Colorado,
      71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an
      edible product. Trial of new products was associated with greater odds of
      experiencing an unexpected high after controlling for age, gender, education,
      mental health status, current marijuana or hashish use, and mean amount of
      marijuana or hashish consumed in the past month (OR=2.13, p<0.001). Individuals
      who reported having used edibles had greater odds of experiencing an unexpected
      high, after controlling for the same set of variables (OR=1.56, p<0.05).
      CONCLUSION: People who try new marijuana or hashish products, or use edible
      marijuana or hashish products, are at greater risk for an unexpected high. It is
      possible that some negative outcomes associated with marijuana use and unexpected
      highs may be averted through a better understanding of how to use product
      packaging to communicate with consumers.

PMID- 28514696
TI  - Alcohol use disorders in Iran: Prevalence, symptoms, correlates, and comorbidity.
AB  - BACKGROUND: For nearly four decades, alcohol production and consumption has been
      banned in the Islamic country of Iran. However, little is known about the extent
      of alcohol use and associated problems in the country. The paper aims to present
      findings on the 12-month prevalence, symptoms, severity, correlates, and
      comorbidity of alcohol use disorders in the Iranian population. METHODS: This
      report is based on the 2011 Iranian household Mental Health survey (IranMHS), a
      nationally representative face-to-face household survey with a multi-stage,
      cluster sampling design. A total of 7840 individuals aged 15-64 responded to the
      alcohol section. We assessed 12-month alcohol use disorders according to DSM-IV
      and DSM-5 criteria and harmful use according to the ICD-10 criteria. RESULTS:
      Weighted prevalence of using alcohol at least once in the past 12 months was
      5.7%. The prevalence of 12-month alcohol use disorders was 1% according to DSM-IV
      criteria and 1.3% according to DSM-5. Harmful use was reported in 0.6%. Alcohol
      use disorders were markedly more common in men than women with an odds ratio (OR)
      of 13.3. It was also more prevalent in never-married versus married individuals
      (OR=2.5) and in those living in urban versus rural areas (OR=2.4). Among those
      with alcohol use disorders, 46.3% had a concurrent mood or anxiety disorder.
      Aggressive behaviors and injuries were more likely in those with alcohol use
      disorders. CONCLUSION: Although Iran has a low level of alcohol use, its adverse
      consequences including use disorders, aggression, and injuries are moderately
      common and raise serious public health concerns.

PMID- 28514697
TI  - Lipoprotein-associated phospholipase A2 and risks of coronary heart disease and
      ischemic stroke in the general population: A systematic review and meta-analysis.
AB  - BACKGROUND: This study investigated the associations between lipoprotein
      associated phospholipase A2 (Lp-PLA2) and the risks of coronary heart disease
      (CHD) and ischemic stroke (IS) in the general population. METHODS: PubMed,
      Embase, and the Cochrane Library databases were searched for prospective cohort
      studies published prior to June 2016. Multivariate-adjusted hazard ratios (HRs)
      with 95% confidence intervals (CIs) for CHD and IS risks according to Lp-PLA2
      activity or mass were extracted, pooled, and weighted using random-effects
      modeling. RESULTS: Twelve studies examining Lp-PLA2 activity or mass and long
      term risks of CHD and IS were included. Combined HRs for CHD and IS risks for the
      highest category referring to lowest category of Lp-PLA2 were 1.46 (95% CI: 1.20
      1.78, P<0.001) and 1.58 (95% CI: 1.21-2.07, P=0.001), respectively. The same
      patterns were observed for both mass and activity, with the exception of those
      for CHD. For every 1-standard deviation (SD) increase in Lp-PLA2 activity, CHD
      risk increased by 12% (HR: 1.12, 95% CI: 1.05-1.22, P=0.002); no association
      between 1-SD increases in Lp-PLA2 activity and IS was observed. Lp-PLA2 mass was
      associated with CHD risk (HR: 1.02-1.24, 95% CI: 1.02-1.24, P=0.021). Lp-PLA2
      mass per 1-SD increase was not associated with IS risk. CONCLUSIONS: Greater Lp
      PLA2 activity or mass was associated with an increased risk of CHD and IS;
      however, additional well-designed trials are warranted to confirm this
      association.

PMID- 28514698
TI  - Clinical outcomes and frontal plane two-dimensional biomechanics during the 30
      second single leg stance test in patients before and after hip abductor tendon
      reconstructive surgery.
AB  - BACKGROUND: Hip abductor tendon tears are a common cause of Greater Trochanteric
      Pain Syndrome. Conservative treatments are often ineffective and surgical
      reconstruction may be recommended. This study investigated the improvement in
      clinical outcomes and frontal plane two-dimensional biomechanics during a 30
      second single leg stance test, in patients undergoing reconstruction. We
      hypothesized that clinical scores and pertinent biomechanical variables would
      significantly improve post-surgery, and these outcomes would be significantly
      correlated. METHODS: Twenty-one patients with symptomatic tendon tears underwent
      reconstruction. Patients were evaluated pre-surgery, and at 6 and 12months post
      surgery, using patient-reported outcome measures, assessment of hip abductor
      strength and six-minute walk capacity. Frontal plane, two-dimensional,
      biomechanical variables including pelvis-on-femur angle, pelvic drop, trunk lean
      and lateral pelvic shift, were evaluated throughout a 30-second single leg stance
      test. ANOVA evaluated outcomes over time, while Pearson's correlations
      investigated associations between clinical scores, pain, functional and
      biomechanical outcome variables. FINDINGS: While clinical and functional measures
      significantly improved (P<0.05) over time, no significant group differences
      (P>0.05) were observed in biomechanical variables from pre- to post-surgery.
      While five patients displayed a positive Trendelenburg sign pre-surgery, only one
      was positive post-surgery. Clinical outcomes and biomechanical variables during
      the single leg stance test were not correlated. INTERPRETATION: Despite
      improvements in clinical and functional measures over time, biomechanical changes
      during a weight bearing single leg stance test were not significantly different
      following tendon repair. Follow up beyond 12months may be required, whereby
      symptomatic relief may precede functional and biomechanical improvement.

PMID- 28514699
TI  - Profiling of illicit cocaine seized in China by ICP-MS analysis of inorganic
      elements.
AB  - For the first time in China, the inorganic element profiling of cocaine specimens
      was performed at the National Narcotics Laboratory. An inductive coupled plasma
      mass spectrometry (ICP-MS) method was developed and validated for simultaneous
      analysis of 26 inorganic elements, including sodium (Na), magnesium (Mg),
      aluminuim (Al), potassium (K), calcium (Ca), vanadium (V), chromium (Cr),
      manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn),
      arsenic (As), selenium (Se), molybdenum (Mo), silver (Ag), cadmium (Cd), antimony
      (Sb), barium (Ba), lanthanum (La), cerium (Ce), thallium (Tl), lead (Pb), thorium
      (Th), and uranium (U) in illicit cocaine samples. Ultrasonic assisted dissolution
      was applied for sample preparation. Minimum sample preparation and analysis time
      were required, which was suitable for routine analysis. After the analysis of 183
      cocaine samples seized from 2011 to 2015, the element concentration ranges of
      cocaine sample were obtained. Based on the quantitative data set of 26 inorganic
      elements in 131 linked/un-linked cocaine samples, fifty combinations of pre
      treatment methods and distance/correlation measurements were tested for their
      potential discrimination power for cocaine profiling, and
      normalization+standardization+logarithm (N+S+L)/Cosine correlation exhibited the
      best result. After hierarchical cluster analysis (HCA) analysis of 183 cocaine
      samples, 21 groups of linked samples were found within and between provinces,
      which provide intelligence for case connection and revealing of the distribution
      networks.

PMID- 28514700
TI  - A comparative in situ decomposition study using still born piglets and leaf
      litter from a deciduous forest.
AB  - A cadaver and dead plant organic matter, or litter, are rich energy sources that
      undergo a complex decomposition process, which impact the surrounding
      environmental microbiota. Advances in molecular microbiology techniques, with
      study of the 16S RNA genes, in particular, have highlighted the application of
      forensic ecogenomics in addressing key knowledge gaps. To investigate subsurface
      microbiome shifts as a novel tool to establish "postmortem microbial clock" and
      augment postmortem interval (PMI) and time-since-burial estimations, an in situ
      study with triplicate underground burials of piglets as human taphonomic proxies
      and Quercus robur leaf litter was monitored for 270 days. Changes in microbial
      community structure and composition were related directly to changes in seasonal
      temperature, with microbial shifts more pronounced during the summer. For
      example, Methylococcaceae could be used as seasonal bacterial indicators, from
      winter to summer, in establishing postmortem microbial clock for this site.
      Furthermore, Methylophilaceae (Methylophilales order) and Anaerolineaceae would
      differentiate for the piglet and leaf litter soils, respectively, 180 days after
      internment.

PMID- 28514701
TI  - A biased opinion: Demonstration of cognitive bias on a fingerprint matching task
      through knowledge of DNA test results.
AB  - One study is presented which explores the biasing effects of irrelevant
      contextual information on a fingerprint matching task. Bias was introduced by
      providing the outcomes of a DNA test relating to each fictitious case under
      consideration. This was engineered to suggest either a match, no match, or an
      inconclusive outcome, and was thus either consistent, misleading or unbiased
      depending on the ground truth of each fingerprint pair. The results suggested
      that, when the difficulty of the fingerprint matching task was measurably
      increased, participants became more vulnerable to the biasing information. Under
      such conditions, when performance was good, misleading evidence lowered accuracy,
      and when performance was weaker, consistent evidence improved accuracy. As such,
      the results confirmed existing demonstrations of cognitive bias from contextual
      information in the fingerprint task. Moreover, by taking a process-based
      approach, it became possible to articulate the concerns, and the potential
      solutions, at each stage of the workflow. The results offer value for the
      forensic science community in extending the evidence-base regarding cognitive
      bias, and in articulating routes to improve the credibility of fingerprint
      decisions.

PMID- 28514702
TI  - Nanoscale morphological analysis of soft matter aggregates with fractal dimension
      ranging from 1 to 3.
AB  - While the widespread emergence of nanoscience and nanotechnology can be dated
      back to the early eighties, the last decade has witnessed a true coming of age of
      this research field, with novel nanomaterials constantly finding their way into
      marketed products. The performance of nanomaterials being dominated by their
      nanoscale morphology, their quantitative characterization with respect to a
      number of properties is often crucial. In this context, those imaging techniques
      able to resolve nanometer scale details are clearly key players. In particular,
      atomic force microscopy can yield a fully quantitative tridimensional (3D)
      topography at the nanoscale. Herein, we will review a set of morphological
      analysis based on the scaling approach, which give access to important
      quantitative parameters for describing nanomaterial samples. To generalize the
      use of such morphological analysis on all D-dimensions (1D, 2D and 3D), the
      review will focus on specific soft matter aggregates with fractal dimension
      ranging from just above 1 to just below 3.

PMID- 28514703
TI  - Bacterial infections and hepatic encephalopathy in liver cirrhosis-prophylaxis
      and treatment.
AB  - Infections are common among patients with liver cirrhosis. They occur more often
      in cirrhotic patient groups than in the general population and result in higher
      mortality. One reason for this phenomenon is bacterial translocation from the
      intestinal lumen that occurs as a consequence of intestinal bacterial overgrowth,
      increased permeability and decreased motility. The most common infections in
      cirrhotic patients are spontaneous bacterial peritonitis and urinary tract
      infections, followed by pneumonia, skin and soft tissue infections. Intestinal
      bacterial overgrowth is also responsible for hyperammonemia, which leads to
      hepatic encephalopathy. All of these complications make this group of patients at
      high risk for mortality. The role of antibiotics in liver cirrhosis is to treat
      and in some cases to prevent the development of infectious complications. Based
      on our current knowledge, antibiotic prophylaxis should be administered to
      patients with gastrointestinal hemorrhage, low ascitic fluid protein
      concentration combined with liver or renal failure, and spontaneous bacterial
      peritonitis as a secondary prophylaxis, as well as after hepatic encephalopathy
      episodes (also as a secondary prophylaxis). In some cases, the use of non
      antibiotic prophylaxis can also be considered. Current knowledge of the treatment
      of infections allows the choice of a preferred antibiotic for empiric therapy
      depending on the infection location and whether the source of the disease is
      nosocomial or community-acquired.

PMID- 28514704
TI  - Guillain-Barre Syndrome, variants & forms fruste: Reclassification with new
      criteria.
AB  - OBJECTIVES: This study aimed to evaluate the clinical and electrophysiological
      characteristics of various distinctive classical and localised Guillain-Barre
      syndrome (GBS) subtypes. PATIENTS AND METHODS: Clinical characteristics and
      electrophysiological data of sixty-one consecutive patients admitted between 2012
      and 2015 were systematically analysed and reclassified according to the new GBS
      clinical classification. Neurophysiology was evaluated with Hadden et al.'s vs
      recently proposed Rajabally et al.'s criteria. Functional severity and clinical
      outcome of various GBS subtypes were ascertained. RESULTS: All patients initially
      identified as GBS or related disorders can be sub-classified into having
      classical GBS (41, 67%), classic Miller-Fisher Syndrome (MFS) (6, 10%),
      Pharyngeal-cervical-brachial (PCB) (3, 5%), paraparetic GBS (4, 7%), bifacial
      weakness with paresthesia (3, 5%), acute ophthalmoparesis (AO) (1, 2%) and
      overlap syndrome (3, 5%): one (2%) with GBS/Bickerstaff brainstem encephalitis
      overlap and 2 (3%) with GBS/MFS overlap. Greater proportion of axonal classical
      GBS (67% vs 55%, p=0.372) seen with Rajabally et al.'s criteria and a
      predominantly axonal form of paraparetic variant (75%) independent of
      electrodiagnostic criteria were more representative of Asian GBS cohort.
      Classical GBS patients had lowest admission and discharge Medical Research
      Council Sum Score (MRCSS), greater functional disability and longest length of in
      patient stay. Twenty (20/21, 95%) patients who needed mechanical ventilation had
      classical GBS. Patients required repeated dose of intravenous immunoglobulin
      (5/6, 3%) or plasma exchange (4/4, 100%) more frequently had axonal form of
      classical GBS. CONCLUSION: Phenotype recognition based on new GBS clinical
      classification, supported by electrodiagnostic study permits more precise
      clinical subtypes determination and outcome prognostication.

PMID- 28514705
TI  - A topologically diverse family of fluoride channels.
AB  - Dual-topology proteins are likely evolutionary antecedents to a common motif in
      membrane protein structures, the inverted repeat. A family of fluoride channels,
      the Flucs, which protect microorganisms, fungi, and plants against cytoplasmic
      fluoride accumulation, has representatives of all topologies along this
      evolutionary trajectory, including dual-topology homodimers, antiparallel
      heterodimers, and, in eukaryotes, fused two-domain proteins with an inverted
      repeat motif. Recent high-resolution crystal structures of dual-topology
      homodimers, coupled with extensive functional information about both the
      homodimers and two-domain Flucs, provide a case study of the co-evolution of fold
      and function.

PMID- 28514707
TI  - Influence of fumigants on sunflower seeds: Characteristics of fumigant desorption
      and changes in volatile profiles.
AB  - Fumigation of transport containers is common practice to protect stored products
      from pests. Yet little is known about the desorption times and effects of the
      highly toxic gases used in this process. To shed light on the behavior of
      fumigants in real food, we treated sunflower seeds (Helianthus annuus L.) with
      100ppm phosphine (PH3), methyl bromide (MeBr) or 1,2-dichloroethane (DCE) for
      72h. The compound concentrations in the air were then analyzed by thermal
      desorption/2D gas chromatography coupled to mass spectrometry and flame
      photometric detection (TD-2D-GC-MS/FPD). A desorption time of several months was
      observed for DCE, whereas PH3 and MeBr were outgassed in a matter of days. To
      investigate possible interactions between gases and constituents of the seeds,
      non-fumigated, fumigated and outgassed samples were analyzed by headspace solid
      phase microextraction GC-MS. We observed significantly different volatile
      profiles in fumigated and subsequently outgassed seeds compared to non-fumigated
      seeds. Whereas PH3-treated seeds released far more terpenoids, the volatile
      pattern of seeds exposed to DCE revealed significantly fewer terpenoids but more
      aldehydes. These changes are likely to affect food aroma characteristics.

PMID- 28514706
TI  - Evaluation of behavioral change after adenotonsillectomy for obstructive sleep
      apnea in children with autism spectrum disorder.
AB  - BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) may affect daily
      cognitive functioning in children. The aims of our study were two-fold. The first
      aim was to detect, using the Child Behavior Checklist (CBCL), whether
      adenotonsillectomy (AT) for the treatment of OSA improved the behavior of
      children with autism spectrum disorder (ASD). The second aim was to identify
      characteristics for behavioral improvement following the treatment of OSA in
      these children with ASD. METHODS: The behaviors of ASD children aged 5-14 years
      diagnosed as having OSA (n=30) were evaluated using CBCL before and after AT.
      CBCL evaluation of ASD children without OSA at two time points with the same
      interval served as a control (n=24). We statistically examined the two groups. In
      addition, we conducted a paired t-test to assess changes in CBCL Tscores between
      the improved group and unchanged/deteriorated group to identify characteristics
      that may affect behavioral changes following OSA treatment. RESULTS: After AT, T
      scores of the CBCL scales were significantly improved in the OSA group, but no
      change was observed in the control. A paired t-test revealed that the improved
      group had significantly higher scores on the CBCL pre-AT than the
      unchanged/deteriorated group in ASD children with OSA after OSA treatment.
      CONCLUSIONS: Behavioral problems were significantly improved following AT in ASD
      children with OSA. Early detection and treatment of children with OSA is
      essential to prevent behavioral problems and to support mental development.

PMID- 28514708
TI  - The effect of lamb carcase weight and GR depth on the production of value-added
      cuts - A short communication.
AB  - Times for the progressive breakdown of 95 lamb carcases were recorded to
      determine the impact of carcase weight and GR tissue depth on the time and
      therefore cost to produce value added retail cuts. Further analysis also assessed
      the potential to use these carcase traits as predictors of fabrication times.
      Regression modeling demonstrated there was a limited ability to predict the
      difference in time to fabricate mid value-added (R2=0.18) and extreme value-added
      (R2=0.12) cuts compared to traditional cuts, suggesting that other factors need
      to be considered. However, this study highlighted the significant increases in
      time required to fabricate more value-added cuts and to breakdown heavier
      carcases. Furthermore, this study demonstrated the changes to the saleable meat
      yield as the degree of fabrication increased, such that the average product
      prices increased ($20.64/kg for mid value added and $28.72/kg for extreme value
      added) compared to traditional retail cuts ($15/kg) to offset the increased
      labour of fabricating value-added cuts.

PMID- 28514709
TI  - Protein adsorption on implant metals with various deformed surfaces.
AB  - The adsorption of proteins has great influence on the biocompatibility,
      lubrication and corrosion properties of implantable metals. The subsurface
      microstructure of metals can be easily changed during the manufacturing or
      service processes and it is easily ignored. The same chemical composition but
      with various surface microstructures can result in very different adsorption
      behaviour. In this study, mechanical polishing, electrochemical polishing and
      shot peening methods were used to generate different gradient deformed surfaces
      for CoCrMo alloys. The increase of the residual compressive stress and the
      decrease of grains to a nano-size on the deformed subsurface can effectively
      enhance the activity of metal atoms and improve the element diffusion, that is
      helpful in forming a more compact passive film. This can increase the contents of
      oxides on the surface, and then enhance the electrostatic force and increase the
      surface's positive charge density as well as adsorption sites. All of the above
      facilitated the adsorption of the negatively charged albumin onto the alloy
      surface.

PMID- 28514710
TI  - Multi-layered nanogels with MMP-sheddable PEG masks: Preparation and promotion of
      tumor cell uptake by controlling surface characteristics.
AB  - We describe a facile and effective poly(ethylene glycol) (PEG) coating method
      that has not been used previously for decoration of nanogels. Layer-by-layer
      (LbL) assembly was the technique of choice to introduce PEG onto the surface of
      multi-layered nanogels (MLNGs). Pegylated MLNGs were prepared simply by
      sequentially dispersing nanogels in solutions of cationic polymer, anionic
      polymer, and modified PEGs, and each coating step was validated by measuring
      changes in size and surface charge. Particularly, a peptide linker that is
      cleavable by matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment was
      introduced between PEG layer and nanogels because it is known that PEG reduces
      the uptake of nanoparticles in tumor cells due to its high mobility. In vitro
      cell studies demonstrated that MLNGs with MMP-cleavable PEGs enhanced the
      particle uptake up to 3 times in tumor cells due to unmasking of PEG brushes as
      compared to pegylated MLNGs without MMP-sensitive peptide linkers.

PMID- 28514711
TI  - Self-assembly of DNA-porphyrin hybrid molecules for the creation of antimicrobial
      nanonetwork.
AB  - DNA derived well-controlled arrangement of porphyrins has emerged as promising
      hybrid nanostructures. Exceptional biocompatibility and DNA-directed surface
      addressability coupled with rich symmetry features of the porphyrin have made
      these hybrid nanostructures attractive candidates for potential biomedical and
      biotechnological applications. However, the noteworthy photophysical properties
      of porphyrin and related molecules when present in DNA based nanostructures are
      yet to be explored fully and should be a matter of intense research that may
      unearth a plethora of interesting applications of these nanostructures. Herein,
      we demonstrate the construction of novel self-assembled DNA-porphyrin hybrid
      nanonetworks that utilize the porphyrin core for antibacterial applications.
      Porphyrin derivative with four pendant NH2 groups was synthesized and conjugated
      with the 5'-PO4 of ss-DNA by solution phase phosphoramidation coupling reaction.
      The conjugation was followed by DNA hybridization mediated self-assembly to form
      DNA-porphyrin hybrid nanonetwork. The enhanced antimicrobial property of the
      nanonetwork was envisioned following light irradiation at relevant wavelength. In
      line with this, comparative antimicrobial activities against gram-negative
      (Escherichia coli BL-21) and gram-positive bacteria (Staphylococcus aureus) have
      been studied. Interestingly, DNA-porphyrin nanonetwork afforded highly efficient
      and coherent photoinduced reactive oxygen species (ROS) generation to display
      antimicrobial activity against Staphylococcus aureus. The escalated and coherent
      ROS generation from the nanonetworks was attributed to the ordered placement of
      the porphyrins that inhibits self-quenching. Our work points out to a good
      alternative for antibiotic free strategies for preservation of biological
      materials and other applications.

PMID- 28514712
TI  - Nitrogen doped carbon dots derived from Sargassum fluitans as fluorophore for DNA
      detection.
AB  - This work focused on the use of waste seaweed Sargassum fluitans (S. fluitans) as
      carbon source precursor to prepare nitrogen doped carbon dots (NCDs) by
      hydrothermal method. High resolution transmission electron microscopic (HR-TEM)
      studies revealed that the synthesized water soluble NCDs are in the size range of
      2-8nm and exhibits excellent fluorescent properties with a quantum yield of
      18.2%. Elemental nitrogen in NCDs was evidenced by X-ray photoelectron
      spectroscopy (XPS) and Fourier transformed infrared spectrum (FT-IR). The
      phytochemical analysis of S. fluitans using 1H NMR and 13C NMR revealed the
      presence of few amino acids which act as nitrogen source in the preparation of
      NCDs. Application of NCDs as fluorophore for double stranded DNA, single stranded
      DNA and RNA detection was highlighted in this study. Excellent fluorescent
      tagging abilities of NCDs with the biological nucleic acids were evidenced using
      gel electrophoresis. Significant increase in fluorescence was observed upon
      tagging of NCDs with nucleic acids and this particular phenomenon helps better in
      visualizing the nucleic acids. All three nucleic acids i.e. double stranded DNA,
      single stranded DNA and RNA showed similar phenomenon upon tagging with NCDs.
      Thus synthesized NCDs may be used as an alternate fluorophore for commercial
      toxic organic staining agents to visualize nucleic acids.

PMID- 28514713
TI  - Pattern recognition receptors and coordinated cellular pathways involved in
      tuberculosis immunopathogenesis: Emerging concepts and perspectives.
AB  - Pattern Recognition Receptors (PRRs) play a central role in the recognition of
      numerous pathogens, including Mycobacterium tuberculosis, resulting in activation
      of innate and adaptive immune responses. Besides Toll Like Receptors, C-type
      Lectin Receptors and Nod Like Receptors are now being recognized for their
      involvement in inducing immune response against M. tuberculosis infection.
      Although, a functional redundancy of the PRRs has also been reported in many
      studies, emerging evidences support the notion that a cooperative and coordinated
      response generated by these receptors is critical to sustain the full immune
      control of M. tuberculosis infection. Many of the PRRs are now found to be
      involved in various cellular host defenses, such as inflammasome activation,
      phagosome biogenesis, endosomal trafficking, and antigen processing pathways that
      are all very critical for an effective immune response against M. tuberculosis.
      In support, polymorphism in several of these receptors has also been found
      associated with increased susceptibility to tuberculosis in humans. Nonetheless,
      increasing evidences also show that in order to enhance its intracellular
      survival, M. tuberculosis has also evolved multiple strategies to subvert and
      reprogram PPR-mediated immune responses. In light of these findings, this review
      analyzes the interaction of bacterial and host factors at the intersections of
      PRR signaling pathways that could provide integrative insights for the
      development of better vaccines and therapeutics for tuberculosis.

PMID- 28514714
TI  - Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and
      inflammatory response through MAPK/Wnt/NF-kappaB pathways.
AB  - Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of
      osteoporosis. However, little information is available about the effects of CT on
      osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on
      the treatment of OA, as well as the underlying mechanisms. Chondrocytes were
      isolated from immature mice and then were incubated with lipopolysaccharide
      (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2,
      and/or the inhibitors of MAPK/Wnt/NF-kappaB pathway. Thereafter, cell viability,
      apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression
      levels of cartilage synthesis protein key factors, cartilage-derived
      morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein
      (SOX9), and MAPK/Wnt/NF-kappaB pathways key factors were determined. CT
      significantly reversed LPS-induced cell viability decrease, apoptosis increase,
      the inflammatory factors and NO secretion, the abnormally expression of cartilage
      synthesis proteins and the activation of MAPK/Wnt/NF-kappaB pathways (P<0.05). In
      addition, we observed that administration of the inhibitors of MAPK/Wnt/NF-kappaB
      pathways statistically further increased the levels of CDMP1 and SOX9 (P<0.05).
      Suppression of BMP-2 decreased the levels of CDMP1 and SOX9 and activated
      MAPK/Wnt/NF-kappaB pathways, and could partially abolish CT-modulated the
      expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-kappaB pathways key factors
      (P<0.05). The results showed that CT protects chondrocytes from LPS-induced
      apoptosis and inflammatory response by regulating BMP-2 and thus blocking
      MAPK/Wnt/NF-kappaB pathways.

PMID- 28514715
TI  - Impact of physician education and availability of parameters regarding esophageal
      pressure and transpulmonary pressure on clinical decisions involving ventilator
      management.
AB  - PURPOSE: This study investigated the effects of physician education and the
      availability of Peso and PL data on physicians' decisions regarding ventilator
      management during specific simulated clinical conditions. MATERIALS AND METHODS:
      The study was a prospective, before-after study using a case scenario-based
      questionnaire and a case simulator device comprising an Avea ventilator and an
      artificial lung and esophagus, which was connected to a Series 1101 Electronic
      Breathing Simulator. The 99 physicians participating in the study were provided
      with five simulated cases with on-time ventilator graphics without Peso and PL
      and completed a questionnaire on decisions they would make regarding ventilator
      management of the cases. Then, after receiving instruction on Peso and PL, they
      were given the same cases along with ventilator graphics that included Peso and
      PL. RESULTS: After receiving instruction and data on Peso and PL, statistically
      significant numbers of physicians changed their answers regarding ventilator
      management decisions in all five cases. CONCLUSIONS: Providing education and data
      for Peso and PL had a significant effect on physician decisions regarding
      ventilator management in simulated cases. The use of case scenario-based
      education with simulator devices for physicians may hasten worldwide
      understanding and clinical application of Peso and PL.

PMID- 28514716
TI  - C-reactive protein, procalcitonin and interleukin-6 kinetics in pediatric
      postoperative patients.

PMID- 28514717
TI  - Quantification of active ingredients in semi-solid pharmaceutical formulations by
      near infrared spectroscopy.
AB  - Near infrared (NIR) spectroscopy is increasingly gaining significance in the
      pharmaceutical industry for quality and in-process control. However, the
      potential of this method for quantitative quality control in pharmacies has long
      been neglected and little data is available on its application in analysis of
      creams and ointments. This study evaluated the applicability of NIR spectrometer
      with limited wavelength range (1000-1900nm) for quantitative quality control of
      six different dermatological semi-solid pharmaceutical preparations. Each
      contained a frequently used active ingredient in a common concentration either in
      a water-free lipid base or in an aqueous cream matrix. Based on direct NIR
      transflectance measurements through standardized glass beakers and partial least
      squares (PLS) multivariate calibration, quantitative models were generated
      comparing several data pre-processing methods Whereas difficulties were observed
      for mixtures containing 2% (w/w) metronidazole or 4% (w/w) erythromycin, content
      determination was possible with sufficient accuracy for salicylic acid (5 %
      (w/w)) and urea (10% (w/w)) in hydrophilic as well as in lipophilic formulations
      meeting the limit of a maximum deviation of+/-5% (relative) from the reference
      values. Exemplarily, one of the methods was successfully validated according to
      the EMA Guideline, determining several figures of merit such as specificity,
      linearity, accuracy, precision and robustness.

PMID- 28514718
TI  - Exploring the neuroprotective effects of ginkgolides injection in a rodent model
      of cerebral ischemia-reperfusion injury by GC-MS based metabolomic profiling.
AB  - Cerebral ischemia-reperfusion (I/R) injury usually contributes to mortality and
      disability after ischemic stroke. Ginkgolides injection (GIn), a standard
      preparation composed of ginkgo diterpene lactones extract, is clinically used for
      neuroprotective treatment on reconvalescents of cerebral infarction. However, the
      understanding about its therapeutic mechanism is still lacking. In this study, a
      gas chromatography-mass spectrometry (GC-MS) based metabolomic approach coupled
      with multivariate data analysis (MVDA) was applied to explore the neuroprotective
      effects of GIn in a rodent model of focal ischemic stroke induced by transient
      middle cerebral artery occlusion (tMCAO). Metabolomic profiling revealed a series
      of metabolic perturbations that underlie the cerebral I/R pathological events.
      GIn can reverse the I/R induced brain metabolic deviations by modulating multiple
      metabolic pathways, such as glycolysis, Krebs cycle, pentose phosphate pathway
      (PPP), gamma-aminobutyrate (GABA) shunt and lipid metabolism. Moreover, the main
      bioactive components of GIn were distributed to brain tissue much more easily in
      tMCAO rats than in normal rats after an intravenous administration, suggesting
      that the increased cerebral exposure to ginkgolides in I/R pathological condition
      potentially facilitated the neuroprotective effects of GIn by directly targeting
      at brain. The present study provided valuable information for our understanding
      about metabolic changes of cerebral I/R injury and clinical application of GIn.

PMID- 28514719
TI  - Multiway analysis methods applied to the fluorescence excitation-emission dataset
      for the simultaneous quantification of valsartan and amlodipine in tablets.
AB  - In this study, excitation-emission matrix datasets, which have strong overlapping
      bands, were processed by using four different chemometric calibration algorithms
      consisting of parallel factor analysis, Tucker3, three-way partial least squares
      and unfolded partial least squares for the simultaneous quantitative estimation
      of valsartan and amlodipine besylate in tablets. In analyses, preliminary
      separation step was not used before the application of parallel factor analysis
      Tucker3, three-way partial least squares and unfolded partial least squares
      approaches for the analysis of the related drug substances in samples. Three-way
      excitation-emission matrix data array was obtained by concatenating excitation
      emission matrices of the calibration set, validation set, and commercial tablet
      samples. The excitation-emission matrix data array was used to get parallel
      factor analysis, Tucker3, three-way partial least squares and unfolded partial
      least squares calibrations and to predict the amounts of valsartan and amlodipine
      besylate in samples. For all the methods, calibration and prediction of valsartan
      and amlodipine besylate were performed in the working concentration ranges of
      0.25-4.50MUg/mL. The validity and the performance of all the proposed methods
      were checked by using the validation parameters. From the analysis results, it
      was concluded that the described two-way and three-way algorithmic methods were
      very useful for the simultaneous quantitative resolution and routine analysis of
      the related drug substances in marketed samples.

PMID- 28514720
TI  - New application for haplotype-specific extraction: Separation of mitochondrial
      DNA mixtures.
AB  - A particularly challenging aspect of forensic casework is the accurate
      interpretation of samples that contain DNA from more than one contributor, since
      DNA analysis of specific identification markers often results in ambiguous mixed
      profiles. Physically separating the various haploid components of a diploid or
      polyploid DNA sample or of a specimen containing DNA from multiple individuals
      can resolve this problem. We adapted and combined previously developed methods of
      haplotype-specific extraction (HSE) to separate and analyze mitochondrial DNA
      (mtDNA) in samples containing DNA from two individuals. After optimizing
      conditions and probes, we performed HSE to separate mitochondrial DNA mixtures,
      which manifest as mixed nucleotide calls at single base positions. We were able
      to subsequently identify the DNA of the two individuals by sequencing. Based on
      our findings from this proof-of-concept experiment, this novel assay will be
      useful for distinguishing among the mtDNA of individuals in mixed DNA samples.

PMID- 28514721
TI  - Impact of GH administration on athletic performance in healthy young adults: A
      systematic review and meta-analysis of placebo-controlled trials.
AB  - OBJECTIVE: Illicit use of growth hormone (GH) as a performance-enhancing drug
      among athletes is prevalent, although the evidence of such effects in healthy,
      young subjects is sparse. We therefore performed a meta-analysis of published
      studies on the effect of GH administration on body composition, substrate
      metabolism, and athletic performance in healthy, young subjects. DESIGN: The
      English-language based databases PubMed, EMBASE, and Cochrane Central Register of
      Controlled Trials were searched, and eligible articles were reviewed in
      accordance with the PRISMA guidelines. Fifty-four potentially relevant articles
      were retrieved of which 11 were included in this analysis comprising 254
      subjects. RESULTS: Administration of GH significantly increased lean body mass
      (p<0.01) and decreased fat mass (p<0.01). In addition, GH increased the
      exercising levels of glycerol (p=0.01) and free fatty acids (p<0.01), but did not
      alter the respiratory quotient during exercise (p=0.30). GH significantly
      increased anaerobic exercise capacity (p<0.01) in the only study which
      investigated this, but did not over weeks to months improve muscle strength
      (p=0.36) or maximum oxygen uptake (p=0.89). CONCLUSION: GH administration elicits
      significant changes in body composition, but does not increase either muscle
      strength or aerobic exercise capacity in healthy, young subjects.

PMID- 28514722
TI  - The interventional effect of new drugs combined with the Stupp protocol on
      glioblastoma: A network meta-analysis.
AB  - OBJECTIVE: New therapeutic agents in combination with the standard Stupp protocol
      (a protocol about the temozolomide combined with radiotherapy treatment with
      glioblastoma was research by Stupp R in 2005) were assessed to evaluate whether
      they were superior to the Stupp protocol alone, to determine the optimum
      treatment regimen for patients with newly diagnosed glioblastoma. PATIENTS AND
      METHODS: We implemented a search strategy to identify studies in the following
      databases: PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang, and VIP, and
      assessed the quality of extracted data from the trials included. Statistical
      software was used to perform network meta-analysis. RESULTS: The use of novel
      therapeutic agents in combination with the Stupp protocol were all shown to be
      superior than the Stupp protocol alone for the treatment of newly diagnosed
      glioblastoma, ranked as follows: cilengitide 2000mg/5/week, bevacizumab in
      combination with irinotecan, nimotuzumab, bevacizumab, cilengitide 2000mg/2/week,
      cytokine-induced killer cell immunotherapy, and the Stupp protocol. In terms of
      serious adverse effects, the intervention group showed a 29% increase in the
      incidence of adverse events compared with the control group (patients treated
      only with Stupp protocol) with a statistically significant difference (RR=1.29;
      95%CI 1.17-1.43; P<0.001). The most common adverse events were thrombocytopenia,
      lymphopenia, neutropenia, pneumonia, nausea, and vomiting, none of which were
      significantly different between the groups except for neutropenia, pneumonia, and
      embolism. CONCLUSIONS: All intervention drugs evaluated in our study were
      superior to the Stupp protocol alone when used in combination with it. However,
      we could not conclusively confirm whether cilengitide 2000mg/5/week was the
      optimum regime, as only one trial using this protocol was included in our study.

PMID- 28514723
TI  - Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a
      germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic
      invasive ductal breast carcinoma.
AB  - We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC
      and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and
      metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a
      tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved
      in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC
      variant is a moderate penetrance allele resulting in an approximately twofold
      increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing
      were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the
      presence of several genomic hits within the double-strand DNA damage pathway
      (CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor
      profiling did not show an obvious DNA repair deficiency signature. However, even
      though the LMS displayed clear malignant features, its genomic profiling revealed
      several characteristics classically associated with leiomyomas including a
      translocation, t(12;14), with one breakpoint disrupting RAD51B and the other
      breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1 This is
      the first report of LMS genomic profiling in a patient with the germline
      CHEK2:c.1100delC variant and an additional diagnosis of metastatic invasive
      ductal breast carcinoma. We also describe a possible mechanistic relationship
      between leiomyoma and LMS based on genomic and transcriptome data. Our findings
      suggest that RAD51B translocation and HMGA2 overexpression may play an important
      role in LMS oncogenesis.

PMID- 28514730
TI  - Circulating microRNAs as novel biomarkers of ALK-positive nonsmall cell lung
      cancer and predictors of response to crizotinib therapy.
AB  - Circulating microRNAs are potential diagnostic and predictive biomarkers, but
      have not been investigated for patients with anaplastic lymphoma kinase (ALK)
      positive lung cancer. In this exploratory study, we sought to identify potential
      plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA
      microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n =
      3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21
      microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC,
      including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s
      rRNA as the most stable endogenous control gene using geNorm and NormFinder
      algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK
      negative NSCLC patients (n = 32) were quantified using real-time reverse
      transcriptase quantitative polymerase chain reaction. The expression levels of
      miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive
      NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating
      characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel
      were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values
      of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%,
      respectively. Increased plasma levels of miR-660-5p after crizotinib treatment
      predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362
      5p were significantly associated with progression-free survival (p = 0.015).
      Thus, in this preliminary investigation, we identified a potential panel of 3
      microRNAs for distinguishing between patients with ALK-positive and ALK-negative
      NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for
      response to crizotinib treatment.

PMID- 28514733
TI  - Role of intravoxel incoherent motion MR imaging in preoperative assessing HER2
      status of gastric cancers.
AB  - PURPOSE: To explore the role of intravoxel incoherent motion (IVIM) magnetic
      resonance (MR) imaging in evaluating human epidermal growth factor receptor 2
      (HER2) status of gastric cancers preoperatively. RESULTS: The apparent diffusion
      coefficient (ADC) and pure diffusion coefficient (D) values correlated positively
      with HER2 scores of gastric cancers significantly (r = 0.276, P = 0.048; r =
      0.481, P < 0.001, respectively). The ADC and D values of HER2 positive gastric
      cancers were significantly higher than those of HER2 negative tumors (P = 0.033,
      0.007, respectively). With a cut-off value of 1.321 and 1.123 * 10-3 mm2/sec, the
      ADC and D values could distinguish HER2 positive gastric cancers from HER2
      negative ones with an area under the curve of 0.733 and 0.762, respectively (P =
      0.023, 0.011, respectively). MATERIALS AND METHODS: Fifty-three patients with
      gastric cancers underwent IVIM MR imaging preoperatively. The values of ADC, D,
      pseudo diffusion coefficient (D*) and perfusion related fraction (f) of the
      lesions were obtained. Partial correlation test including tumor volume was
      performed to analyze correlations between IVIM values and HER2 scores excluding
      the impact of tumor size. IVIM parameters of gastric cancers with different HER2
      status were compared using independent samples t test. Diagnostic performance of
      IVIM parameters in distinguishing HER2 positive gastric cancers from negative
      ones was tested with receiver operating characteristic analysis. CONCLUSIONS: We
      confirmed the feasibility of IVIM MR imaging in preoperative assessment of HER2
      status of gastric cancers, which might make up the shortfall of biopsy and
      facilitate personalized treatment for patients with gastric cancers.

PMID- 28514734
TI  - Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin
      sulfate during human intervertebral disc degeneration.
AB  - Intervertebral disc degeneration (IDD) is characterized by dehydration and loss
      of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has
      been found to be the water-binding molecule that played a key role in IDD.
      Although investigators have reported that inflammatory cytokines are involved in
      the reduction of chondroitin sulfate in IDD, but the underlying mechanism is
      unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin
      sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role
      and regulatory mechanism in IDD is not fully studied. Here, we set out to
      investigate the function and regulatory roles of these factors during IDD
      development. We found that among these chondroitin sulfate glycosyltransferases,
      CHSY-1/2/3 are significantly down-regulated in severe IDD samples than mild IDD
      samples. In vitro experiments revealed that Interleukin-1beta and Tumor Necrosis
      Factor-alpha stimulation led to significant reduction of CHSY-1/2/3 at protein
      level than mRNA level in NP cells, indicating a post-transcriptional regulatory
      mechanisms are involved. By computational prediction and analysis, we found that
      inflammatory cytokines stimulated microRNA-194 and -515 target CHSY-1/2/3 mRNA
      and significantly interrupt their translation and downstream chondroitin sulfate
      deposition. Inhibition of microRNA-194 and -515 however, significantly rescued
      CHSY-1/2/3 expressions and chondroitin sulfate deposition. These findings
      together demonstrated a vital role of inflammatory stimulated microRNAs in
      promoting intervertebral disc degeneration by interrupt chondroitin sulfate
      synthesis, which may provide new insights into the mechanism and therapeutic
      approaches in IDD.

PMID- 28514744
TI  - Characterization of mouse serum exosomal small RNA content: The origins and their
      roles in modulating inflammatory response.
AB  - In the last decade, although studies on exosomal microRNAs (miRNAs) derived from
      serum and other body fluids have increased dramatically; the contents and
      biological significance of serum exosomes under normal conditions remain unclear.
      In the present study, we profiled the small RNA content of mouse serum exosomes
      (mSEs) using small RNAseq and found that fragments of transfer RNAs (tRNAs) and
      miRNAs were the two predominant exosomal RNA species, accounting for
      approximately 60% and 10% of mapped reads, respectively. Moreover, 466 known and
      5 novel miRNAs were identified from two independent experiments, among which the
      five most abundant miRNAs (miR-486a-5p, miR-22-3p, miR-16-5p, miR-10b-5p and miR
      27b-3p) accounted for approximately 60% of all the aligned miRNA sequences. As
      inferred from the identities of the well known cell- or tissue-specific miRNAs,
      mSEs were primarily released by RBCs, liver and intestinal cells. Bioinformatics
      analysis revealed over half of the top 20 miRNAs by abundance were involved in
      inflammatory responses and further in vitro experiments demonstrated that mSEs
      potently primed macrophages towards the M2 phenotype. To the best of our
      knowledge, this is the first study to profile small RNAs from mSEs. In addition
      to providing a reference for future biomarker studies and extrapolating their
      origins, our data also suggest the roles of mSEs in maintaining internal
      homeostasis under normal conditions.

PMID- 28514745
TI  - Combating acquired resistance to trastuzumab by an anti-ErbB2 fully human
      antibody.
AB  - Trastuzumab resistance is a common problem that impedes the effectiveness of
      trastuzumab in ErbB2-amplified cancers. About 70% of ErbB2-amplified breast
      cancers do not respond to trastuzumab (de novo resistance), and the majority of
      the trastuzumab-responsive cancers progress within 1 year (acquired resistance).
      Different mechanisms exist between de novo and acquired resistance. Innate
      resistance mechanisms are mainly independent of ErbB2 receptor activity, and
      acquired resistance involves with alterations depending on ErbB2 activity. We
      previously reported H2-18, an ErbB2 domain I-specific antibody, which could
      circumvent de novo resistance to trastuzumab. Here, we modeled the development of
      acquired resistance by treating human gastric cancer cell line NCI-N87 with
      trastuzumab to obtain the trastuzumab-resistant subline, NCI-N87-TraRT. Next, we
      investigated the antitumor efficacy of H2-18 in NCI-N87-TraRT cell line. H2-18
      exhibited a significantly greater antitumor activity in NCI-N87-TraRT tumor
      bearing nude mice than pertuzumab and trastuzumab, either alone or in
      combination. The unique ability of H2-18 to overcome acquired resistance may be
      attributable to its potent programmed cell death-inducing activity, which was
      probably mediated by RIP1-ROS-JNK-c-Jun pathway. In conclusion, H2-18 may have
      the potential as an effective agent to circumvent acquired resistance to
      trastuzumab in ErbB2-overexpressing cancers.

PMID- 28514746
TI  - Diagnostic and prognostic values of endothelial-cell-specific molecule-1 with
      malignant pleural effusions in patients with non-small cell lung cancer.
AB  - Over-expressed endothelial-cell-specific molecule-1 (ESM-1) in tumor vascular
      endothelium contributes to tumor angiogenesis, metastasis, and poor prognosis.
      However, the content of ESM-1 in pleural effusion is unclear. A retrospective
      study was carried out to investigate the diagnostic and prognostic values of ESM
      1 with malignant pleural effusions in patients with non-small cell lung cancer
      (NSCLC). ESM-1 levels in malignant pleural effusion (MPE) from 70 patients with
      NSCLC and 50 cases of benign pleural effusion (BPE) were measured using enzyme
      linked immunosorbent assay. Receiver operating characteristic (ROC) curve was
      calculated to assess the diagnostic value of ESM-1. Survival curves were
      performed by Kaplan-Meier method and survival characteristics were compared by
      log-rank test. Univariable and multivariate Cox proportional hazards model were
      carried out to analysis the significance of different prognostic factors for
      overall survival (OS). ESM-1 levels were significantly higher in MPE than those
      in BPE (p < 0.001). By ROC curve analysis, with a cutoff level of 19.58 ng/ml,
      the accuracy, sensitivity, and specificity for ESM-1 diagnosis MPE were 82.5%,
      81.4%, and 84.0%, respectively. Moreover, NSCLC patients with pleural fluid ESM-1
      levels below 19.58 ng/ml had significant longer OS than those patients with
      higher levels (22.09 months vs. 11.49 months, p = 0.003). Multivariate survival
      analysis showed that high MPE ESM-1 level was an independent prognostic factor
      (HR, 1.007; p = 0.039) for the OS of NSCLC patients. This study showed that ESM-1
      level in pleural effusion could be a potential diagnostic and prognostic marker
      in NSCLC patients with MPE.

PMID- 28514747
TI  - Diagnostic value of using 18F-FDG PET and PET/CT in immunocompetent patients with
      primary central nervous system lymphoma: A systematic review and meta-analysis.
AB  - BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)
      and PET/CT have become two of the most powerful tools for malignant lymphoma
      exploration, but their diagnostic role in primary central nervous system lymphoma
      (PCNSL) is still disputed. The purpose of our study is to identify the usefulness
      of 18F-FDG PET and PET/CT for detecting PCNSL. RESULTS: A total of 129 patients,
      obtained from eight eligible studies, were included for this systematic review
      and meta-analysis. The performance of 18F-FDG PET and PET/CT for diagnosing PCNSL
      were as follows: the pooled sensitivity was 0.88 (95% CI: 0.80-0.94), specificity
      was 0.86 (95% CI: 0.73-0.94), positive likelihood ratio (PLR) was 3.99 (95% CI:
      2.31-6.90), negative likelihood ratio (NLR) was 0.11 (95% CI: 0.04-0.32), and
      diagnostic odds ratio (DOR) was 33.40 (95% CI: 10.40-107.3). In addition, the
      area under the curve (AUC) and Q index were 0.9192 and 0.8525, respectively.
      MATERIALS AND METHODS: PubMed/MEDLINE, Embase and Cochrane Library were
      systematically searched for potential publications (last updated on July 16th,
      2016). Reference lists of included articles were also checked. Original articles
      that reported data on patients who were suspected of having PCNSL were considered
      suitable for inclusion. The sensitivities and specificities of 18F-FDG PET and
      PET/CT in each study were evaluated. The Stata software and Meta-Disc software
      were employed in the process of data analysis. CONCLUSIONS: 18F-FDG PET and
      PET/CT showed considerable accuracy in identifying PCNSL in immunocompetent
      patients and could be a valuable radiological diagnostic tool for PCNSL.

PMID- 28514737
TI  - Integration of phytochemicals and phytotherapy into cancer precision medicine.
AB  - Concepts of individualized therapy in the 1970s and 1980s attempted to develop
      predictive in vitro tests for individual drug responsiveness without reaching
      clinical routine. Precision medicine attempts to device novel individual cancer
      therapy strategies. Using bioinformatics, relevant knowledge is extracted from
      huge data amounts. However, tumor heterogeneity challenges chemotherapy due to
      genetically and phenotypically different cell subpopulations, which may lead to
      refractory tumors. Natural products always served as vital resources for cancer
      therapy (e.g., Vinca alkaloids, camptothecin, paclitaxel, etc.) and are also
      sources for novel drugs. Targeted drugs developed to specifically address tumor
      related proteins represent the basis of precision medicine. Natural products from
      plants represent excellent resource for targeted therapies. Phytochemicals and
      herbal mixtures act multi-specifically, i.e. they attack multiple targets at the
      same time. Network pharmacology facilitates the identification of the complexity
      of pharmacogenomic networks and new signaling networks that are distorted in
      tumors. In the present review, we give a conceptual overview, how the problem of
      drug resistance may be approached by integrating phytochemicals and phytotherapy
      into academic western medicine. Modern technology platforms (e.g. "-omics"
      technologies, DNA/RNA sequencing, and network pharmacology) can be applied for
      diverse treatment modalities such as cytotoxic and targeted chemotherapy as well
      as phytochemicals and phytotherapy. Thereby, these technologies represent an
      integrative momentum to merge the best of two worlds: clinical oncology and
      traditional medicine. In conclusion, the integration of phytochemicals and
      phytotherapy into cancer precision medicine represents a valuable asset to
      chemically synthesized chemicals and therapeutic antibodies.

PMID- 28514748
TI  - A transcriptional complex composed of ER(alpha), GATA3, FOXA1 and ELL3 regulates
      IL-20 expression in breast cancer cells.
AB  - Interleukin-20 (IL-20) is a member of the IL-10 family. IL-20 expression is
      regulated by a transcription elongation factor, Ell3, in estrogen receptor
      positive (ER(+)) breast cancer cells. In this study, we demonstrated that
      ER(alpha), GATA3 and FOXA1 form a transcriptional complex with Ell3 to regulate
      IL-20 expression in ER(+) breast cancer cells. We also determined that GATA3 and
      FOXA1 share a binding site with ER(alpha) in the interleukin-20 promoter.
      Furthermore, we found that FOXA1 represses IL-20 expression, whereas GATA3 and
      ER(alpha) activate it. In addition, we demonstrated that Ell3 associates with
      ER(alpha) to increase its binding affinity to the IL-20 promoter, which may
      prevent FOXA1 binding to the same region of this promoter. Our results expand
      upon the current understanding of the regulatory mechanism of IL-20 in cancer.

PMID- 28514749
TI  - A variant in SIRT2 gene 3'-UTR is associated with susceptibility to colorectal
      cancer.
AB  - SIRT2 is a member of sirtuin family and is associated with cell growth in various
      cancers. In this study, we searched for variants in functional region of SIRT2
      gene and identify rs2015 and rs2241703 in the 3'UTR with minor allele frequency
      >0.05 in Chinese Han Beijing population from 1000 Genomes Project. We then
      genotyped these two variants in 842 colorectal cancer (CRC) patients and 1,718
      healthy controls using Taqman genotyping assay. Association between variants and
      risk of CRC is calculated using logistic regression adjusted for sex and age. We
      found that rs2015C was significantly associated with increased risk of CRC.
      Compared with CC genotype carriers, CA genotype and AA genotype carriers were
      associated with CRC susceptibility with OR being 0.79 (95% CI: 0.65-0.96, P =
      0.019) and 0.73 (95% CI: 0.58-0.92, P = 0.009), respectively. When stratified by
      sex and age, significant associations were observed only in males (OR = 0.82, 95%
      CI: 0.71-0.96, P = 0.010) for rs2015, but not females (OR = 0.90, 95% CI: 0.73
      1.10, P = 0.287). It is suggested that the sequence including rs2015C allele lies
      within a binding site for the full seed region of hsa-miR-376a-5p. Through a
      systematic interrogate of variants in the functional region of SIRT2 gene, we
      identified rs2015 was significantly associated with CRC susceptibility, providing
      new insights into the carcinogenesis of CRC.

PMID- 28514750
TI  - Epigenome-wide association study in hepatocellular carcinoma: Identification of
      stochastic epigenetic mutations through an innovative statistical approach.
AB  - Hepatocellular carcinoma (HCC) results from accumulation of both genetic and
      epigenetic alterations. We investigated the genome-wide DNA methylation profile
      in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium
      HumanMethylation 450K BeadChip array. An innovative analytical approach has been
      adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and
      peritumoral tissues showed a different epigenetic profile, mainly characterized
      by loss of DNA methylation in HCC. Total number of SEMs was significantly higher
      in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and
      correlated with tumor grade. A significant positive association emerged between
      SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection
      status. A restricted number of SEMs resulted to be shared by more than 90% of HCC
      tumor samples and never present in peritumoral tissue. This analysis allowed the
      identification of four epigenetically regulated candidate genes (AJAP1, ADARB2,
      PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC
      showed a methylation profile completely deregulated and very far from adjacent
      non-cancerous liver tissues. The SEM analysis provided valuable clues for further
      investigations in understanding the process of tumorigenesis in HCC.

PMID- 28514751
TI  - Large-scale clinical validation of biomarkers for pancreatic cancer using a mass
      spectrometry-based proteomics approach.
AB  - We performed an integrated analysis of proteomic and transcriptomic datasets to
      develop potential diagnostic markers for early pancreatic cancer. In the
      discovery phase, a multiple reaction monitoring assay of 90 proteins identified
      by either gene expression analysis or global serum proteome profiling was
      established and applied to 182 clinical specimens. Nine proteins (P < 0.05) were
      selected for the independent validation phase and quantified using stable isotope
      dilution-multiple reaction monitoring-mass spectrometry in 456 specimens. Of
      these proteins, four proteins (apolipoprotein A-IV, apolipoprotein CIII, insulin
      like growth factor binding protein 2 and tissue inhibitor of metalloproteinase 1)
      were significantly altered in pancreatic cancer in both the discovery and
      validation phase (P < 0.01). Moreover, a panel including carbohydrate antigen 19
      9, apolipoprotein A-IV and tissue inhibitor of metalloproteinase 1 showed better
      performance for distinguishing early pancreatic cancer from pancreatitis (Area
      under the curve = 0.934, 86% sensitivity at fixed 90% specificity) than
      carbohydrate antigen 19-9 alone (71% sensitivity).Overall, we present the panel
      of robust biomarkers for early pancreatic cancer diagnosis through bioinformatics
      analysis that combined transcriptomic and proteomic data as well as rigorous
      validation on a large number of independent clinical samples.

PMID- 28514753
TI  - Impact of age on the diagnostic performances and cut-offs of APRI and FIB-4 for
      significant fibrosis and cirrhosis in chronic hepatitis B.
AB  - AIMS: Assessing the diagnostic performances of APRI and FIB-4 using age as a
      categorical marker. METHODS: 822 chronic hepatitis B (CHB) patients were
      included. Using METAVIR scoring system as a reference, the performances of APRI
      and FIB-4 were compared between patients aged>=30 and patients aged<30 years.
      RESULTS: The APRI AUROC in patients aged<30 years was lower than that in patients
      aged>=30 years for significant fibrosis (0.61 vs 0.70, p<0.001) and cirrhosis
      (0.64 vs 0.78, p<0.001). The FIB-4 AUROC in patients aged<30 years was lower than
      that in patients aged>=30 years for significant fibrosis (0.57 vs 0.65, p<0.001)
      and cirrhosis (0.63 vs 0.72, p<0.001). Using specificity>=90%, the APRI cut-off
      in patients aged<30 years was lower than patients aged>=30 years for significant
      fibrosis (1.0 vs 1.2) and cirrhosis (1.2 vs 1.5). Using sensitivity>=90%, the
      APRI cut-off in patients aged<30 years was also lower than patients aged>=30
      years for significant fibrosis (0.2 vs 0.4) and cirrhosis (0.3 vs 0.5). Using
      specificity>=90%, the FIB-4 cut-off in patients aged<30 years was lower than that
      in patients aged>=30 years for significant fibrosis (1.2 vs 2.1) and cirrhosis
      (1.4 vs 2.6). Using sensitivity>=90%, the FIB-4 cut-off in patients aged<30 years
      was also lower than that in patients aged>=30 years for significant fibrosis (0.5
      vs 0.8) and cirrhosis (0.8 vs 1.2). CONCLUSIONS: Evaluation of the diagnostic
      performances of APRI and FIB-4 should take age into consideration.

PMID- 28514752
TI  - alphaMSH inhibits adipose inflammation via reducing FoxOs transcription and
      blocking Akt/JNK pathway in mice.
AB  - Alpha melanocyte stimulating hormone (alphaMSH) abates inflammation in multiple
      tissues, while Forkhead box proteins O (FoxOs) stimulate inflammatory cascade.
      However, the relationship between alphaMSH and FoxOs in adipose inflammation
      remains unclear. In this study, we used LPS-induced inflammation model, attempted
      to interpret the function of alphaMSH in inflammation and the interactions with
      FoxOs. Results indicated that upon inflammatory situation, the secretion of
      alphaMSH and the expression of its receptor MC5R were greatly decreased, but
      FoxOs expressions were elevated. After the treatment with alphaMSH, LPS-induced
      adipose inflammation together with FoxOs expressions was significantly reduced.
      Conversely, when Foxo1, Foxo3a or Foxo4 overexpressed in alphaMSH treated
      inflammatory mouse model, all the anti-inflammatory impacts of alphaMSH were
      found disappeared. We further studied the mechanisms by which alphaMSH exerts its
      anti-inflammatory impacts and how FoxOs reverse alphaMSH's function. Foxo4 was
      found as a negative regulator for MC5R transcription in alphaMSH inhibited
      inflammation. Moreover, a negative role was found of alphaMSH in regulating both
      Akt and JNK signal pathways by observing the enhanced the anti-inflammatory
      impacts of pathway-specific inhibitors with alphaMSH treatment. Our findings
      demonstrate alphaMSH plays a key role in the prevention of adipose inflammation
      and inflammatory diseases by down-regulating Akt/JNK signal pathway and
      negatively interacting with FoxOs, which brings up alphaMSH as a novel candidate
      factor in the adipose anti-inflammation process in obesity.

PMID- 28514754
TI  - A hydrophobic residue in the TALE homeodomain of PBX1 promotes epithelial-to
      mesenchymal transition of gastric carcinoma.
AB  - Pre-B-cell leukemia homeobox 1 (PBX1) was originally identified as a proto
      oncogene in human leukemia. Although this protein has been shown to contribute to
      cellular development and tumorigenesis, the role of PBX1 in gastric carcinoma
      (GC) remains unclear. In this study, we observed increased expression of PBX1 in
      GC tissues compared with adjacent normal tissues. This increase in PBX1
      expression levels negatively correlated with HOXB9 mRNA expression and was also
      associated with malignancy and metastasis. PBX1 promoted proliferation and
      metastasis of GC cells both in vitro and in vivo.These phenomena were also
      accompanied by epithelial-to-mesenchymal transition (EMT). Additionally, we
      observed that PBX1 promotes the expression of tumor growth and angiogenic
      factors. A structural model of the PBX1-HOX complex revealed that hydrophobic
      binding between PBX1 and the hexapeptide motif might be required for EMT
      induction. This analysis also demonstrated that the Phe252 residue in the first
      helix of the TALE homeodomain is involved in the latter hydrophobic binding
      reaction. In vitro data from PBX1 mutants suggest that PBX1 cannot promote
      tumorigenesis of GC cells via EMT induction when Phe252 residues lose
      hydrophobicity. It is likely that the presence of this residue is essential in
      facilitating hydrophobic binding with the hexapeptide motif. These findings
      suggest that PBX1 may be a potential target for GC treatment and this study
      provides a platform to elucidate the molecular mechanisms that underpin the role
      of PBX1 in GC tumorigenesis.

PMID- 28514755
TI  - A novel serum based biomarker panel has complementary ability to preclude
      presence of early lung cancer for low dose CT (LDCT).
AB  - Low Dosage Computerized Tomography (LDCT) has been shown to improve early
      detection of lung cancer and mortality rates in high-risk individuals, which was,
      however, limited by specifically coverage for heavy smokers and high rates of
      false positivity. Here, we aim to investigate a novel biomarker for early
      detection of lung cancer, and further extend to concentrate high-risk subjects
      for increasing specificity and coverage of LDCT. We performed retrospective
      blinded evaluation of lung cancer and healthy controls in training and validation
      cohorts. Macrophage inhibitory cytokine 1 (MIC-1) alone and panel were assessed.
      Our data showed the sensitivity of MIC-1 was 72.2% and 67.1% for lung cancer
      diagnosis and early diagnosis respectively, at 96.6% specificity, which were
      significantly higher than Cyfra21-1, NSE CA125, CEA and SCC. At 90% specificity,
      the panel of MIC-1, Cyfra21-1, CA125 and CEA provided 89.5% sensitivity for early
      diagnosis of lung cancer, which could be used to concentrate the high-risk
      subjects for further LDCT screening. We conclude that MIC-1 have great capacity
      in early lung cancer diagnosis. The algorithmic panel of MIC-1, Cyfra21-1, CA125
      and CEA could be used to refine the preselection criteria of high-risk subjects,
      and thus might facilitate the widespread implementation of LDCT screening.

PMID- 28514756
TI  - Elevated CRP levels predict poor outcome and tumor recurrence in patients with
      thymic epithelial tumors: A pro- and retrospective analysis.
AB  - OBJECTIVE: Scarce information exists on the pathogenesis of thymic epithelial
      tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine
      tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed
      to investigate the clinical relevance of CRP in patients with TETs. RESULTS:
      Pretreatment CRP serum concentrations were significantly elevated in patients
      with TETs, particularly TCs and metastatic TETs. After complete tumor resection
      CRP serum concentrations were decreased (p = 0.135) but increased significantly
      in case of tumor recurrence (p = 0.001). High pretreatment CRP was associated
      with significantly worse 5- and 10-year freedom-from recurrence (FFR) (p = 0.010)
      and was a negative prognostic factor for FFR (HR 3.30; p = 0.015). IL-6 (not IL
      1beta) serum concentrations were significantly elevated in patients with TETs but
      we did not detect CRP tissue expression in TETs. MATERIALS AND METHODS:
      Pretreatment CRP serum concentrations were retrospectively analyzed from 128
      surgical patients (1990-2015). In a subset of 68 patients longitudinal analysis
      of CRP was performed. Additionally, immunohistochemical tumor CRP expression and
      serum concentrations of interleukin (IL)-6 and IL-1beta were measured.
      CONCLUSIONS: Hence, diagnostic measurement of serum CRP might be useful to
      indicate highly aggressive TETs and to make doctors consider tumor recurrences
      during oncological follow-up.

PMID- 28514757
TI  - Adhesion- and stress-related adaptation of glioma radiochemoresistance is
      circumvented by beta1 integrin/JNK co-targeting.
AB  - Resistance of cancer stem-like and cancer tumor bulk cells to radiochemotherapy
      and destructive infiltration of the brain fundamentally influence the treatment
      efficiency to cure of patients suffering from Glioblastoma (GBM). The interplay
      of adhesion and stress-related signaling and activation of bypass cascades that
      counteract therapeutic approaches remain to be identified in GBM cells. We here
      show that combined inhibition of the adhesion receptor beta1 integrin and the
      stress-mediator c-Jun N-terminal kinase (JNK) induces radiosensitization and
      blocks invasion in stem-like and patient-derived GBM cultures as well as in GBM
      cell lines. In vivo, this treatment approach not only significantly delays tumor
      growth but also increases median survival of orthotopic, radiochemotherapy
      treated GBM mice. Both, in vitro and in vivo, effects seen with beta1
      integrin/JNK co-inhibition are superior to the monotherapy. Mechanistically, the
      in vitro radiosensitization provoked by beta1 integrin/JNK targeting is caused by
      defective DNA repair associated with chromatin changes, enhanced ATM
      phosphorylation and prolonged G2/M cell cycle arrest. Our findings identify a
      beta1 integrin/JNK co-dependent bypass signaling for GBM therapy resistance,
      which might be therapeutically exploitable.

PMID- 28514758
TI  - BCL2L10 positive cells in bone marrow are an independent prognostic factor of
      azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia.
AB  - Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic
      (MDS) patients can also improve overall survival (OS) in elderly acute myeloid
      leukemia (AML) patients ineligible for intensive chemotherapy, but reliable
      biological markers predicting response and OS in patients treated with AZA are
      lacking. In a preliminary study, we found that an increase of the percentage of
      BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA
      resistance. In this study, we assessed prospectively by flow cytometry the
      prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients
      (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow
      blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells
      inversely correlated with response to AZA and OS independently of the
      International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R).
      Specifically, OS was significantly lower in patients with more than 10% BCL2L10
      positive cells (median 8.3 vs 22.9 months in patients with less than 10%
      positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a
      biomarker for azacitidine response and OS, with a potential impact in clinical
      practice.

PMID- 28514761
TI  - Zbtb38 is a novel target for spinal cord injury.
AB  - Spinal cord injury (SCI) is currently incurable since treatments applied to
      clinic are limited to minimizing secondary complications and the mechanisms of
      injury-induced spinal cord damage are poorly understood. Zbtb38, also called
      CIBZ, is highly expressed in spinal cord and it functions as a negative regulator
      in SCI-induced apoptosis. We show here that Zbtb38 is downregulated under
      endoplasmic reticulum (ER) stress, which promotes ER stress-associated apoptosis
      in human bone marrow neuroblastoma cells. In the traumatic SCI mice, ER stress
      presented in injured spinal cord induced repression of Zbtb38 expression and
      triggered Zbtb38-mediated apoptosis. ChIP-QPCR analysis revealed that ATF4, an ER
      stress inducible transcription factor, directly activated Zbtb38 transcription by
      binding to the Zbtb38 promoter. However, this binding was significantly reduced
      following SCI, leading to a sharp decrease in Zbtb38 expression. Restoring Zbtb38
      function in injured spinal cord by injection of lentivirus containing Zbtb38 into
      SCI mice, significantly alleviated secondary damage of spinal cord with decreased
      ER stress-associated apoptosis and partially recovered spinal cord functions.
      These findings demonstrate that restoration of Zbtb38 expression can reduce
      secondary tissue damage after SCI, and suggest that a therapeutic strategy for
      targeting Zbtb38 may promote functional recovery of spinal cord for patients with
      SCI.

PMID- 28514759
TI  - Charge reversible calcium phosphate lipid hybrid nanoparticle for siRNA delivery.
AB  - Bcl-2 gene is an important target to treat lung cancer. The small interference
      RNA (siRNA) of Bcl-2 gene (siBcl-2) can specifically silence Bcl-2 gene. However,
      naked siBcl-2 is difficult to accumulate in the tumor tissue to exert its
      activity. In this paper, a calcium phosphate lipid hybrid nanoparticle that
      possessed charge reversible property was prepared to enhance the activity of
      siBcl-2 in vivo. The average diameter and zeta potential of siBcl-2 loaded
      calcium phosphate lipid hybrid nanoparticles (LNPS@siBcl-2) were 80 nm and -13 mV
      at pH7.4 whereas the diameter and zeta potential changed to 1506 nm and +9 mV at
      pH5.0. LNPS@siBcl-2 could efficiently deliver siBcl-2 to the cytoplasm and
      significantly decreased the expression of Bcl-2 in A549 cells. Moreover, the in
      vivo experimental results showed that most of the Cy5-siBcl-2 accumulated in
      tumor tissue after LNPS@Cy5-siBcl-2 was administered to tumor-bearing mice by
      tail vein injection. Meanwhile, the expression of Bcl-2 was decreased but the
      expression of the BAX and Caspase-3 was increased in tumor tissue. LNPS@siBcl-2
      significantly inhibited the growth of tumor in tumor-bearing mice without any
      obvious systemic toxicity. Thus, the charge reversible calcium phosphate lipid
      hybrid nanoparticle was an excellent siBcl-2 delivery carrier to improve the
      activity of siBcl-2 in vivo. LNPS@siBcl-2 has potential in the treatment of lung
      cancer.

PMID- 28514762
TI  - Novel circular RNA expression profiles reflect progression of patients with
      hypopharyngeal squamous cell carcinoma.
AB  - Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, have been
      shown to have important roles in a number of diseases, including several types of
      cancers. We hypothesized that circRNAs are involved in the pathogenesis of
      hypopharyngeal squamous cell carcinoma (HSCC). To test our hypothesis, we
      initially compared the expression profiles of circRNAs in 4 paired HSCC and
      adjacent normal tissue samples by using a circRNA microarray. The microarray data
      showed that 2392 circRNAs, including 1304 upregulated and 1088 downregulated
      circRNA transcripts, were significantly dysregulated in the HSCC tissues. The 10
      most dysregulated circRNAs from the microarray analysis were further validated in
      another 32 pairs of specimens using quantitative real-time polymerase chain
      reaction assays. These circRNAs might sponge microRNAs (miRNAs) in predicted
      circRNA-miRNA-mRNA networks. Bioinformatics analysis was also performed to
      predict possible pathways in which these networks might be involved. Finally, we
      analyzed the interaction between validated circRNAs and their potential cancer
      related miRNA targets. We are the first to comprehensively delineate the
      expression profiles of circRNAs in HSCC and to provide potential candidates for
      future mechanism studies. Our study is potentially of critical significance in
      uncovering the roles of circRNAs in HSCC.

PMID- 28514764
TI  - TRIM32 affects the recovery of motor function following spinal cord injury
      through regulating proliferation of glia.
AB  - Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit
      the axonal regeneration after spinal cord injury (SCI). However, the underlying
      molecular mechanisms remain unclear. In the present study, we identify tripartite
      motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in
      glial cells in the normal uninjured spinal cord, exhibits strong expression in
      both astrocytes and microglia following SCI. We further observe that deficiency
      of TRIM32 results in increased numbers of astrocytes and microglia, which is
      accompanied by enhanced proliferation of both cells and increased secretion of
      interleukin (IL)-1 and IL-10. The axonal regeneration is impaired in the spinal
      cord of TRIM32-/- mice following SCI, which is indicated by increased distances
      of the corticospinal tracts (CST) fiber to the lesion site and less axonal
      sprouting. We further show that deficiency of TRIM32 results in delay motor
      recovery following SCI. Therefore, TRIM32 is a novel essential positive factor
      modulating axonal regeneration and the recovery of motor function following SCI,
      possibly through suppressing proliferation of glial cells.

PMID- 28514765
TI  - BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells
      through PI3K/AKT/mTOR and STAT3 pathways.
AB  - Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be
      involved in cell proliferation, differentiation, apoptosis, migration and
      invasion in several types of tumors, but its role in cervical carcinoma remains
      poorly understood. In this study, we showed that BMX expression exhibits a
      gradually increasing trend from normal cervical tissue to cervical cancer in situ
      and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and
      irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell
      proliferation was significantly decreased. Knockdown of BMX in HeLa and SiHa
      cervical cancer cell lines using two different silencing technologies, TALEN and
      shRNA, inhibited cell growth in vitro and suppressed xenograft tumor formation in
      vivo, whereas overexpression of BMX in the cell line C-33A significantly
      increased cell proliferation. Furthermore, a mechanism study showed that
      silencing BMX blocked cell cycle transit from G0/G1 to S or G2/M phase, and
      knockdown of BMX inhibited the expression of p-AKT and p-STAT3. These results
      suggested that BMX can promote cell proliferation through PI3K/AKT/mTOR and STAT3
      signaling pathways in cervical cancer cells.

PMID- 28514772
TI  - Risk of Onset of Hematological Malignancies in Patients Infected with the
      Hepatitis B Virus: Results from a Large-Scale Retrospective Cohort Study in
      China.
AB  - The hepatitis B virus (HBV) is a major global issue, because an increased risk of
      hepatocellular carcinoma among patients infected with HBV is well established.
      Recently, it has been suggested that HBV is associated with other human cancers.
      However, the association between HBV and the risk of onset of hematological
      malignancies remains controversial. The aim of this large-scale retrospective
      cohort study was to evaluate the association between HBV infection and
      hematological malignancies. A retrospective analysis of 86,115 newly admitted
      patients at Shanghai Ruijin Hospital was performed. A cohort of patients
      previously exposed to HBV (n = 1,874) and a cohort of individuals without a
      positive test for anti-hepatitis B core antigen (anti-HBc; n = 45,118) were
      compared to assess the risk of hematological malignancies. Anti-HBc was positive
      in 61.2% cases and 54.3% controls (p = 0.0001). The risk of B cell non-Hodgkin's
      lymphoma, acute lymphoblastic leukemia, and multiple myeloma was higher in the
      HBV-infected cohort than in the non-HBV-infected cohort. In conclusion, patients
      infected with HBV have a substantially increased risk of hematological
      malignancies.

PMID- 28514771
TI  - Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial
      functional effects in healthy and diseased human myocardium.
AB  - : The current gold standard for prostate cancer treatment is androgen deprivation
      therapy and antiandrogenic agents. However, adverse cardiovascular events
      including heart failure can limit therapeutic use. Istaroxime, which combines Na+
      K+-ATPase (NKA) inhibition with sarco/endoplasmic reticulum Ca2+-ATPase 2a
      (SERCA2a) stimulation, has recently shown promising anti-neoplastic effects in
      prostate cancer (PC) models and may also improve cardiac function. Considering
      the promising anticancer effects of istaroxime, we aimed to assess its functional
      effects on human myocardium. RESULTS: Istaroxime and strophanthidin elicited dose
      dependent positive inotropic effects with a decline in developed force at
      supraphysiological concentrations in human atrial, nonfailing, and failing
      ventricular (ToF) myocardium. Diastolic force and RT50% did not change after
      exposure to both drugs. The maximal developed force in our in-vitro model of
      heart failure (ToF) was significantly higher after istaroxime administration.
      Such a difference did not occur in atrial or nonfailing ventricular trabeculae
      and was not applicable to the diastolic force. MATERIALS AND METHODS: Human
      atrial and ventricular trabeculae were isolated from nonfailing hearts and hearts
      of infants with tetralogy of Fallot (ToF), which were used as an in-vitro model
      of heart failure. The samples were electrically stimulated and treated with
      increasing concentrations of istaroxime and strophanthidin (10 nM-1 MUM).
      Systolic and diastolic force development and relaxation parameters (RT50%) were
      analyzed. CONCLUSIONS: Combined NKA inhibition/SERCA2a stimulation increases
      contractility in atrial, nonfailing, and failing myocardium. Considering that
      heart failure is a potential side effect of current PC treatments, especially in
      elderly patients, istaroxime might combine beneficial cardiac and anti-cancer
      properties.

PMID- 28514773
TI  - A Feasibility Study of the Full Outpatient Conduction of Hematopoietic
      Transplants in Persons with Multiple Sclerosis Employing Autologous Non
      Cryopreserved Peripheral Blood Stem Cells.
AB  - BACKGROUND: With the goal of achieving immune system reset, autologous
      hematopoietic stem cell transplantations have been performed in patients with
      multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six
      consecutive patients with MS were autografted in a single center using non-frozen
      peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with
      cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov
      identifier NCT02674217. RESULTS: One hundred and ninety-four females and 92 males
      were included; the median age was 47. All procedures were started on an
      outpatient basis and only 8 persons needed to be admitted to the hospital during
      the procedure. In order to obtain at least 1 * 106/kg viable CD34 cells, 1-4
      aphereses were performed (median 1). The total number of viable CD34+ cells
      infused ranged between 1 and 19.2 * 106/kg (median 4.6). Patients recovered above
      0.5 * 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals
      needed red blood cells but none needed platelet transfusions. There were no
      transplant-related deaths and the 128-month overall survival of the patients is
      100%. In 82 persons followed up for 3 or more months, the Expanded Disability
      Status Scale diminished from a mean of 5.2-4.9, the best results being obtained
      in relapsing-remitting and primary progressive MS. CONCLUSIONS: It is possible to
      conduct autotransplants for patients with MS employing non-frozen PBSCs and
      outpatient conduction. Additional information is needed to assess the efficacy of
      these procedures in the treatment of patients with MS.

PMID- 28514774
TI  - Demonstration of 5-Methylcytosine-Rich DNA Sequences in Chiroptera.
AB  - 5-Methylcytosine-rich heterochromatic regions were demonstrated in metaphase
      chromosomes of 5 species of Chiroptera by indirect immunofluorescence using a
      monoclonal anti-5-methylcytosine antibody. These species belong to 4 genera and 2
      families and are characterized by divergent karyotypes. One species
      (Glauconycteris beatrix) has an extremely low diploid chromosome number of 2n =
      22 with only meta- to submetacentric elements and remarkably large amounts of
      constitutive heterochromatin located in the centromeric and pericentromeric
      regions of all chromosome pairs. Two species (G. beatrix and Neoromicia cf.
      guineensis) possess X-autosome translocations. In all species, the
      hypermethylated chromosome segments correspond to constitutive heterochromatin,
      and the numbers and positions of hypermethylated chromosome segments in the
      karyotypes are constant and species-specific. In some species (Pipistrellus
      hesperidus, Neoromicia cf. somalicus), there are several smaller chromosome pairs
      in which the bright anti-5-methylcytosine antibody labeling is not restricted to
      constitutively heterochromatic regions but is observed along the whole lengths of
      these chromosomes. The nature of these additional hypermethylated regions is
      discussed. The analysis of 5-methylcytosine-rich chromosome regions elucidates
      valuable data for chiropteran cytogenetics and reflects the high pace of
      evolution of the repetitive DNA fraction in their genomes.

PMID- 28514775
TI  - Metallic and Polymeric Scaffold: Too Soon to Pension the Drug-Eluting Stent.

PMID- 28514776
TI  - Predictive Factors for Developing Venous Thrombosis during Cisplatin-Based
      Chemotherapy in Testicular Cancer.
AB  - BACKGROUND: Malignancies and cisplatin-based chemotherapy are both known to
      correlate with a high risk of venous thrombotic events (VTT). In testicular
      cancer, the information regarding the incidence and reason of VTT in patients
      undergoing cisplatin-based chemotherapy is still discussed controversially.
      Moreover, no risk factors for developing a VTT during cisplatin-based
      chemotherapy have been elucidated so far. PATIENTS AND METHODS: We
      retrospectively analyzed 153 patients with testicular cancer undergoing cisplatin
      based chemotherapy at our institution for the development of a VTT during or
      after chemotherapy. Clinical and pathological parameters for identifying possible
      risk factors for VTT were analyzed. The Khorana risk score was used to calculate
      the risk of VTT. Student t test was applied for calculating the statistical
      significance of differences between the treatment groups. RESULTS: Twenty-six out
      of 153 patients (17%) developed a VTT during chemotherapy. When we analyzed the
      risk factors for developing a VTT, we found that Lugano stage >=IIc was
      significantly (p = 0.0006) correlated with the risk of developing a VTT during
      chemotherapy. On calculating the VTT risk using the Khorana risk score model, we
      found that only 2 out of 26 patients (7.7%) were in the high-risk Khorana group
      (>=3). CONCLUSION: Patients with testicular cancer with a high tumor volume have
      a significant risk of developing a VTT with cisplatin-based chemotherapy. The
      Khorana risk score is not an accurate tool for predicting VTT in testicular
      cancer.

PMID- 28514777
TI  - Direct Measurement of Tissue Oxygenation in Neonates via Resonance Raman
      Spectroscopy: A Pilot Study.
AB  - BACKGROUND: The ability to monitor tissue oxygenation in neonates remains a
      challenge due to limited blood supply and the reliance on invasive procedures.
      Resonance Raman spectroscopy noninvasively measures tissue oxygenation (RRS
      StO2). Peripheral tissue oxygenation using this novel technology has not been
      described in neonates. OBJECTIVES: To examine the relationship between short-term
      RRS-StO2 measurements and central venous saturation (ScvO2) and pulse oximetry
      (SpO2) in preterm and term neonates. METHODS: Ninety-seven term neonates had
      buccal and plantar RRS-StO2 measurements performed. In 15 preterm neonates,
      similar measurements were obtained in conjunction with ScvO2 in the first week of
      life. Simultaneous SpO2 and heart rate were also recorded. RESULTS: In healthy
      neonates, buccal RRS-StO2 values negatively correlated with the day of life. No
      correlation existed between buccal and plantar RRS-StO2 values and ScvO2 or SpO2.
      Greater intra-patient plantar RRS-StO2 variability was seen in preterm neonates
      with increasing respiratory support. CONCLUSIONS: Neonatal RRS-StO2 measurements
      are feasible short term but do not correlate with ScvO2 and SpO2. Healthy
      neonates had greater differences and variability in RRS-StO2 values, illustrating
      an evolving microcirculation not detected with pulse oximetry. Greater RRS-StO2
      variability in sick neonates requiring respiratory support may indicate
      microcirculatory instability despite being within target SpO2 ranges. Further
      study is needed to establish if RRS-StO2 monitoring is an accurate representation
      of tissue oxygenation.

PMID- 28514778
TI  - Validation of the Five-Factor Model of the Arabic Version of the Positive and
      Negative Syndrome Scale in Schizophrenia.
AB  - BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is a widely used
      assessment for patients with schizophrenia across clinical and research settings.
      This scale allows the classification of the psychotic symptoms to better
      understand the psychopathology in patients with schizophrenia. There are no
      available data on the different components of psychopathology in Arab patients
      with schizophrenia. OBJECTIVES: This study examined the factor structure of the
      validated Arabic version of the PANSS in a sample of Arab patients with
      schizophrenia. METHODS: The Arabic version of the PANSS was administered to 101
      patients with schizophrenia, and principal component analysis (PCA) was carried
      out after the cross-cultural adaptation and validation of this version. RESULTS:
      This sample had more males (66.3%) than females (33.7%) with a mean age of 35.03
      years (SD = 9.99). PCA showed that 28 items loaded on 5 components: cognitive,
      negative, excited, depressed and positive. These factors explained 63.19% of
      variance. The 2 remaining items, grandiosity and somatic concerns, did not load
      well on any of these components. CONCLUSION: Our results support the common 5
      dimension PANSS model shown in other cultures with different languages.
      Nevertheless, there were minor differences, which could reflect cultural or
      semantic differences.

PMID- 28514779
TI  - Low Back Pain in Pregnancy: Investigations, Management, and Role of Neuraxial
      Analgesia and Anaesthesia: A Systematic Review.
AB  - BACKGROUND: Low back pain (LBP) is commonly experienced during pregnancy and is
      often poorly managed. There is much ambiguity in diagnostic work-up, appropriate
      management and decision-making regarding the use of neuraxial analgesia and
      anaesthesia during labour and delivery in these patients. This systematic review
      summarises the evidence regarding investigations, management strategies and
      considerations around performing neuraxial blocks for pregnant women with LBP.
      METHODS: We searched 3 databases and reviewed literature concerning LBP in
      pregnancy with regards to diagnostic modalities, management strategies and use of
      neuraxial techniques for facilitating labour and delivery. RESULTS: In all, we
      included 78 studies in this review, with 32 studies concerning diagnostic
      investigations, 56 studies involving management strategies, and 4 studies
      regarding the use of neuraxial techniques for labour and delivery. SUMMARY: MRI
      is the safest investigative modality for LBP in pregnancy. Antenatal educational
      programmes, exercise and steroid injections into the epidural space or sacroiliac
      joints may help with pain management. Worsening neurological deficits, vertebral
      fractures and tumours may need surgical management. There is limited evidence on
      challenges of performing neuraxial blocks in the peripartum period for analgesia
      and anaesthesia, but there is a potential for increased risk of neurological
      complications in parturients with pre-existing neurological deficits.

PMID- 28514780
TI  - Two Distinct BCL2 Rearrangements, Each Observed in 2 Independent Subclones,
      Evolving from a Founder Clone with Trisomy 12 in a Unique Case of Chronic
      Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

PMID- 28514781
TI  - Hepcidin: Homeostasis and Diseases Related to Iron Metabolism.
AB  - Iron is an essential metal for cell survival that is regulated by the peptide
      hormone hepcidin. However, its influence on certain diseases is directly related
      to iron metabolism or secondary to underlying diseases. Genetic alterations
      influence the serum hepcidin concentration, which can lead to an iron overload in
      tissues, as observed in haemochromatosis, in which serum hepcidin or defective
      hepcidin synthesis is observed. Another genetic imbalance of iron is iron
      refractory anaemia, in which serum concentrations of hepcidin are increased,
      precluding the flow and efflux of extra- and intracellular iron. During the
      pathogenesis of certain diseases, the resulting oxidative stress, as well as the
      increase in inflammatory cytokines, influences the transcription of the HAMP gene
      to generate a secondary anaemia due to the increase in the serum concentration of
      hepcidin. To date, there is no available drug to inhibit or enhance hepcidin
      transcription, mostly due to the cytotoxicity described in the in vitro models.
      The proposed therapeutic targets are still in the early stages of clinical
      trials. Some candidates are promising, such as heparin derivatives and
      minihepcidins. This review describes the main pathways of systemic and genetic
      regulation of hepcidin, as well as its influence on the disorders related to iron
      metabolism.

PMID- 28514782
TI  - A Systematic Review and Meta-Analysis of Influenza A Virus Infection During
      Pregnancy Associated with an Increased Risk for Stillbirth and Low Birth Weight.
AB  - BACKGROUND/AIMS: Impaired pregnancy outcomes, such as low birth weight are
      associated with increased disease risk in later life, however little is known
      about the impact of common infectious diseases during pregnancy on birth weight.
      The study had two aims: a) to investigate risk factors of influenza virus
      infection during pregnancy, and b) to analyze the impact of influenza virus
      infection on pregnancy outcome, especially birth weight. METHODS: Prospective and
      retrospective observational studies found in PubMed, MEDLINE, Embase, Google
      Scholar, and WangFang database were included in this meta analysis. Data of
      included studies was extracted and analyzed by the RevMan software. RESULTS:
      Pregnant women with anemia (P=0.004, RR=1.46, 95% CI: 1.13-1.88), obesity
      (P<0.00001, RR=1.35, 95% CI: 1.25-1.46) and asthma (P<0.00001, RR=1.99, 95% CI:
      1.67-2.37) had higher rates of influenza virus infection. Regarding birth
      outcomes, influenza A virus infection did not affect the likelihood for cesarean
      section. Mothers with influenza had a higher rate of stillbirth (P=0.04, RR=2.36,
      95% CI: 1.05-5.31), and their offspring had low 5-minute APGR Scores (P=0.009,
      RR=1.39, 95% CI: 1.08-1.79). Furthermore, the rate for birth weight < 2500g
      (P=0.04, RR=1.71, 95% CI: 1.03-2.84) was increased. CONCLUSION: Results of this
      study showed that anemia, asthma and obesity during pregnancy are risk factors
      influenza A virus infection during pregnancy. Moreover, gestational influenza A
      infection impairs pregnancy outcomes and increases the risk for low birth weight,
      a known risk factor for later life disease susceptibility.

PMID- 28514783
TI  - Dialysis Access as an Area of Improvement in Elderly Incident Hemodialysis
      Patients: Results from a Cohort Study from the International Monitoring Dialysis
      Outcomes Initiative.
AB  - BACKGROUND: Commencing hemodialysis (HD) using a catheter is associated with a
      higher risk of adverse outcomes, and early conversion from central-venous
      catheter (CVC) to arteriovenous fistula/graft (non-CVC) improves outcomes. We
      investigated CVC prevalence and conversion, and their effects on outcomes during
      the first year of HD in a multinational cohort of elderly patients. METHODS:
      Patients >=70 years from the MONDO Initiative who commenced HD between 2000 and
      2010 in Asia-Pacific, Europe, North-, and South-America and survived at least 6
      months were included in this investigation. We stratified by age (70-79 years
      [younger] vs. >=80 years [older]) and compared access types (at first and last
      available date) and their changes. We studied the association between access at
      initiation and conversion, respectively, and all-cause mortality using Kaplan
      Meier curve and Cox regression, and predicted the absence of conversion from
      catheter to non-CVC using adjusted logistic regression. RESULTS: In 14,966
      elderly, incident HD patients, survival was significantly worse when using a CVC
      at all times. In Europe, the conversion frequency from CVC to non-CVC was higher
      in the younger fraction. Conversion from non-CVC to CVC was associated with
      worsened outcomes only in the older fraction. CONCLUSION: These results
      corroborate the need for early HD preparation in the elderly HD population.
      Treatment of elderly patients who commence HD with a CVC should be planned
      considering aspects of individual clinical risk assessment. Differences in
      treatment practices in predialysis care specific to the elderly as a population
      may influence access care and conversion rate.

PMID- 28514784
TI  - Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with
      Myocardial Infarction and Abnormal Glucose Tolerance.
AB  - OBJECTIVES: Abnormal glucose tolerance in patients with acute myocardial
      infarction (AMI) is associated with greater mortality and adverse cardiovascular
      effects. As statins possess a range of beneficial pleiotropic effects on the
      cardiovascular system, we sought to assess the cardioprotective effects of
      statins on left ventricular function in patients with AMI in relation to
      glycometabolic state. METHODS: In a prospective, randomized trial, 140 patients
      with AMI were randomized to intensive statin therapy receiving statin loading
      with 80 mg of rosuvastatin followed by 40 mg daily or standard statin therapy.
      Patients were assessed with an oral glucose tolerance test and their left
      ventricular (LV) function was assessed with speckle-tracking echocardiography
      measuring regional longitudinal systolic strain (RLSS) in the infarct area.
      RESULTS: Overall RLSS in the infarct area improved by a mean (+/-SD) of -4.22%
      (+/-5.19) in the intensive-care group and -2.48% (+/-4.01) in the usual-care
      group after 1 month (p = 0.047). In patients with abnormal glucose tolerance,
      RLSS improved by -5.01% (+/-5.28) in the intensive-care group and -2.15% (+/
      4.22) in the usual-care group (p = 0.01). CONCLUSIONS: Early high-dose statin
      treatment improved RLSS in the infarct area in patients with AMI, and a trend of
      greater improvement was seen in patients with abnormal glucose tolerance.

PMID- 28514785
TI  - Effect of Age on the Association of Vascular Access Type with Mortality in a
      Cohort of Incident End-Stage Renal Disease Patients.
AB  - BACKGROUND/AIMS: All hemodialysis (HD) patients are generally recommended to
      create a fistula first; but to create a mature arteriovenous fistula (AVF) can be
      challenging in elderly individuals. It is unclear if elderly incident HD patients
      derive a survival benefit from an AVF over an arteriovenous graft (AVG) or a
      tunneled central venous catheter (TDC). METHODS: We examined the association of
      vascular access type (AVF, AVG, and TDC with and without a maturing AVF/AVG at
      dialysis transition) at HD initiation with all-cause, cardiovascular (CV), and
      infection-related mortality in 46,786 US veterans using Cox models with
      adjustment for confounders. Effect modification by age was examined by examining
      associations in pre-specified age subgroups (<60, 60-<70, 70-<80, and >=80 years
      old), and by including interaction terms. RESULTS: Patients numbering 8,940 (19%)
      started HD with an AVF, 1,090 (3%) with an AVG, 8,262 (18%) with a TDC and a
      maturing AVF/AVG and 28,494 (61%) with a TDC without a maturing AVF/AVG. A total
      of 13,303 all-cause, 4,392 CV, and 1,058 infection-related deaths were observed
      in the first year after HD transition. Compared to patients with AVF, those with
      AVG and TDC with and without maturing AVF/AVG had incrementally higher overall
      risk of all-cause mortality and CV mortality. Only TDC use was associated with
      higher infection-associated mortality. These associations were not modified by
      age. CONCLUSION: Although most of our patients consisted of male veterans and the
      results may not be generalized to the general population, the use of TDCs is
      associated with poor outcomes even in the most elderly incident HD patients.

PMID- 28514786
TI  - Vascular Proliferation of the Thyroid: Potential Histopathological Pitfalls as a
      Consequence of Fine Needle Aspiration.
AB  - OBJECTIVE: Fine needle aspiration biopsy (FNAB) can cause reactive
      histopathological changes, commonly including haemorrhage and granulation tissue.
      The literature describing vascular proliferation after FNAB is sparse. We aimed
      to describe neovascularisation in thyroid gland specimens as a consequence of
      FNAB. STUDY DESIGN: We analysed all thyroid histopathological specimens from the
      Fimlab Laboratories collected between 2010 and 2013 for neovascularisation and
      distortions in the accompanying tissue. We evaluated HE-stained slides and CD31-,
      podoplanin-, and Ki-67-immunostained slides. RESULTS: We observed vascular
      proliferation in 64 out of 787 specimens (8.1%). In these patients, the mean age
      was 62 years, 43 were female and 21 were male. Previous FNAB data were available
      in 49 cases (76.6%). In 51 cases (79.7%), the neovascularisation occupied less
      than 5% of the thyroid gland area. The vessel dilatation was moderate in 28 cases
      (43.8%) and low in 20 cases (31.3%). In tumours, neovessels were detected within
      the tumour and in the surrounding tissue. CONCLUSIONS: Post-FNAB tissue samples
      include dilated newly formed vessels, which pathologists should differentiate
      from rare thyroid vascular tumours. The proposed mechanism is a traumatically
      induced haemorrhage followed by haematoma and thrombosis that resolves by
      recanalisation. A knowledge of tissue alteration is needed to avoid misdiagnoses.

PMID- 28514787
TI  - Delayed Effect of Active Pressure Treatment on Endolymphatic Hydrops.
AB  - OBJECTIVE: To identify eventual correlations between the effect of low-pressure
      treatment and endolymphatic hydrops in Meniere patients. MATERIAL AND METHODS:
      The study group consisted of subjects affected by definite Meniere disease (2015)
      and a severe degree of disability, who received a ventilation tube with or
      without a low-pressure treatment before undergoing a surgical procedure
      (vestibular neurectomy). After the placement of the ventilation tube, the
      subjects were either left alone with the tube or received 1 month of self
      administered low-pressure therapy with a portable device. In all subjects, an
      electrocochleography (ECochG) was performed and specific questionnaires -
      Dizziness Handicap Inventory (DHI) and Functional Scale Level (FSL) - were
      completed before starting either arm of treatment, at the end of treatment, and
      then 3 and 6 months later. RESULTS: All selected subjects presented with an
      ECochG pattern that was indicative of endolymphatic hydrops before starting
      either treatment. At the end of pressure treatment, 80% showed symptomatic
      improvement while maintaining the hydropic ECochG pattern. At the 3-month control
      stage, the hydropic pattern resulted normalized (<0.5) in all the improved
      subjects. CONCLUSIONS: Although 1 month of low-pressure treatment provided a
      positive symptomatological outcome, normalization of the hydropic ECochG
      parameters occurred only at a later time. Therefore, it is possible to assume
      that endolymphatic hydrops could be concurrent with a non-symptomatic stage of
      Meniere disease, and that the anti-hydropic effect of the low-pressure treatment,
      if any, would present with a certain delay after its completion.

PMID- 28514788
TI  - Embodied pain: grasping a thorny problem?

PMID- 28514789
TI  - Growth hormone regulates the sensitization of developing peripheral nociceptors
      during cutaneous inflammation: Erratum.

PMID- 28514790
TI  - Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic
      studies: a NeuPSIG systematic review, Delphi survey, and expert panel
      recommendations: Erratum.

PMID- 28514791
TI  - Impact of targeting adenosine-induced transient venous reconnection in patients
      undergoing pulmonary vein isolation for atrial fibrillation: a meta-analysis of
      3524 patients.
AB  - AIMS: Atrial fibrillation recurrences after pulmonary vein isolation (PVI) are
      not uncommon and are frequently related to pulmonary vein reconnection.
      Adenosine/ATP can reveal dormant pulmonary vein conduction after PVI. Previous
      studies revealed that adenosine-guided Additional ablation could improve
      arrhythmia-free survival. We performed a meta-analysis to assess the impact of
      additional ablation to eliminate adenosine-induced transient pulmonary vein
      reconnection in terms of atrial fibrillation recurrence at follow-up. METHODS:
      MEDLINE/PubMed, Cochrane Library and references reporting atrial fibrillation
      ablation and adenosine/ATP-following PVI were screened, and studies were included
      if they matched inclusion and exclusion criteria. RESULTS: A total of 3524
      patients were enrolled with a median follow-up of 13 (6-20) months. Overall, 70%
      (60-85) of patients in ATP-guided ablation vs. 63% (48-79) in no ATP-guided
      ablation were free of atrial fibrillation at follow-up. Pooled results revealed
      that ATP-guided ablation reduced the risk of atrial fibrillation recurrence of
      42% [odds ratio (OR) 0.58, 0.41-0.81], but this result was primary because of the
      contribution of retrospective over-randomized studies [OR 0.48 (0.35-0.65) vs.
      0.76 (0.42-1.40), respectively]. 3.2% of patients experienced an adverse event.
      ATP-guided ablation is related to a nonsignificant increase in fluoroscopy time
      (OR 1.71, 0.98-2.96) and to a significant increase in procedure time (OR 2.84,
      1.32-6.09). CONCLUSION: Additional ablation aiming to eliminate adenosine-induced
      transient pulmonary vein reconnection failed to reduce the risk of atrial
      fibrillation recurrence at follow-up. Moreover, although adenosine-guided PVI is
      not affected by an augmented risk of adverse events, it is associated with a NS
      increased fluoroscopy exposure and significantly longer procedure duration.
      Further studies are required to identify the actual role of adenosine in PVI.

PMID- 28514793
TI  - Acute Treatment Patterns for Lower Extremity Trauma in the United States: Flaps
      versus Amputation.

PMID- 28514794
TI  - [Editor's Comment].

PMID- 28514792
TI  - Autonomic dysregulation in burnout and depression: evidence for the central role
      of exhaustion.
AB  - Objectives Given the important role of the autonomic nervous system (ANS) in
      stress regulation, astonishingly little is known about ANS functioning in
      burnout, a condition arising after prolonged exposure to work-related stress. The
      current study sought to investigate ANS modulation, as indexed by vagally
      mediated heart rate variability (HRV), in relation to burnout symptomatology to
      (i) distinguish associations between the three dimensions of burnout [emotional
      exhaustion (EE), cynicism, reduced personal accomplishment] and (ii) investigate
      overlap in associations with depressive symptomatology. Methods Assessments of
      vagally-mediated HRV (ie, root mean square of successive differences, RMSSD) were
      conducted in a large population-based sample from the Dresden Burnout Study
      [N=410, mean age 42.2, standard deviation (SD) 11.2 years; 33.4% male]. Vagally
      mediated HRV was assessed for 90 seconds during an emotionally-arousing situation
      (venipuncture, recumbent), a 335-second recumbent recovery period, and a 335
      second seated resting condition. Results Results from multiple linear regression
      analyses revealed that EE was negatively related to RMSSD during venipuncture
      (=beta -0.11, P=0.03) and the seated rest (beta= -0.09, P=0.04) even after
      accounting for established ANS modulators (eg, age, body mass index). This
      pattern was not observed for the other dimensions of burnout. Exploratory
      analyses of depressive symptomatology further revealed that RMSSD was
      significantly and inversely associated with burnout-related symptoms but not with
      the core criteria of depression (eg, depressed mood). Conclusions This study
      presents evidence for a link between exhaustion and reduced vagal function, both
      in burnout and depression, suggesting that ANS modulations may not be disorder
      specific but rather a psychophysiological correlate of an underlying feature
      shared by both conditions.

PMID- 28514796
TI  - ?

PMID- 28514795
TI  - ?

PMID- 28514797
TI  - ?

PMID- 28514798
TI  - [Swallowing Disorders in Tracheo(s)tomized Patients].
AB  - Objective Since many years it has been conjectured that tracheotomy/tracheostomy
      interferes with swallowing and leads to a higher risk of aspiration. The aim of
      this review was to contribute to the discussion whether there is a causal
      relationship between tracheotomy/tracheostomy and dysphagia or only a
      chronological concomitance. Material and Methods Citations for this review rest
      upon a research in PubMed data base of the National Center for Biotechnology
      Information (NCBI). Results Effects of tracheostomy/tracheotomy as well as
      effects of different cannulas on motoric and sensory aspects of deglutition have
      been reviewed. Most papers focused on aspiration. Reported data were extremely
      heterogeneous. Finally no causal relationship between tracheotomy and dysphagia
      could be demonstrated. Conclusions Tracheo(s)tomized patients require a special
      awareness in respect to concomitant dysphagia. However, swallowing problems are
      considered to be primarily caused rather by underlying diseases than by the
      existence of the tracheostomy itself.

PMID- 28514799
TI  - [Rare Differential Diagnosis of Tinnitus and Hearing Impairment].

PMID- 28514800
TI  - [From the Experts Office: Hearing Impairment due Vibration, Infrasound,
      Ultrasound and/or Bodysound?]

PMID- 28514802
TI  - ?

PMID- 28514801
TI  - [Psychooncological Treatment of Patients with Head and Neck Cancer].
AB  - The aim of psychooncological interventions are to facilitate coping with the
      disease, to improve the psychological well-being and quality of life of the
      cancer patients as well as the strengthening of personal and social
      resources.Apart from general strain going along with oncological diseases and its
      treatment, patients with head and neck cancer often also suffer from impairment
      of the most basic human functions (speech, swallowing, food intake).Patients with
      head and neck cancer are one of the most distressed and burdened groups of cancer
      patients.Psychooncological interventions apply proven psychological and
      psychotherapeutic methods and techniques.Psychooncological treatment is based on
      the close interdisciplinary cooperation of different professional groups.

PMID- 28514803
TI  - ?

PMID- 28514804
TI  - [Changes in the Use of Health Insurance Services before and after a Father-Child
      Measure].
AB  - Introduction Since 2002 inpatient preventive and rehabilitative measures for
      fathers and their children (F-C-M) are available in the German health system (SS
      24 and 41 SGB V). So far there is no data on health disorders of the fathers in F
      C-M. The aim of this study is to examine whether participants of F-C-M are more
      prone to health problems than fathers who are not participating in F-C-M and
      whether participation in F-C-M contributes to improved health. To do so, the
      change in the use of outpatient care services is examined and compared to the use
      of mentioned services by fathers who are not participating in an F-C-M. The
      research project is based on the routine data of AOK-Niedersachsen (AOKN).
      Methods Outpatient diagnoses and medications that were billed one year before and
      one year after the measure are used as outcome variables for outpatient use. The
      test sample (N=179) includes all fathers who participated in a F-C-M in 2005-2009
      and were insured throughout. For these fathers, a comparative group of fathers
      who had not participated in a F-C-M (N=717) was formed in parallel. Results The
      investigation has shown that the participants of the F-C-M received more
      diagnoses and medications before and after the measure than fathers without F-C
      M. Fathers under 40 years mostly got fewer diagnoses and medications after the
      measure than before the measure, whereas older people showed a higher claim after
      the measure. The participants of the F-C-M mainly have more F-diagnoses than
      fathers without F-C-M. In addition to that the increase in I-diagnoses and the
      increase in cardiovascular drugs are striking compared to the previous year.
      Conclusion The increased use of the statutory health insurance benefits of
      participants of the F-C-M compared to non-participants indicates that the F-C-M
      is a health-impaired group of insured people. The high number of F-diagnoses
      further illustrates that the participants are particularly affected in this
      indication area. A positive effect of the measure is shown by the fact that
      younger fathers made reduced use of health insurance benefits, while in the case
      of older participants a treatment requirement was still predominant or was
      revealed in the context of the measure.

PMID- 28514805
TI  - Expression and Histopathological Significance of Disabled-2 in Aldosterone
      Producing Adenoma.
AB  - The current pathological diagnosis of aldosterone-producing adenoma (APA) is
      challenging because no histological markers of aldosterone production are
      available in routine practice. A previous study demonstrated that Disabled-2
      (DAB2) is a specific marker of the zona glomerulosa (ZG) in rodents. The aim of
      the present study was to investigate the significance of immunohistochemical
      staining to detect DAB2 in the adrenal tissue of patients with APA. We
      investigated the expression of DAB2 in 36 adrenal glands with APA, 23 adrenal
      glands with cortisol-producing adenoma (CPA), and 33 adrenal glands with non
      functioning adenoma (NFA). Immunohistochemical staining was performed using anti
      DAB2 antibodies on paraffin-embedded sections. We analysed the expression of DAB2
      semi-quantitatively by scoring staining intensity, and assessed the correlation
      of this information with the clinical findings. DAB2 mRNA expression in adenoma
      tissues was evaluated by RT-PCR. DAB2 was highly expressed in the ZG in normal
      human adrenal glands. DAB2 expression was heterogeneous in APA, with spotted,
      strong staining noted in most samples (25 of 36 APA). CPA and NFA also exhibited
      extensive low or moderate DAB2 expression. DAB2 mRNA was significantly increased
      and positively correlated with CYP11B2 in APA (p<0.05). In APA, the DAB2 score
      adjusted for tumour volume was positively correlated with plasma aldosterone
      (p<0.05). Patients with low or moderate DAB2 staining more frequently exhibited
      high blood pressure and were diagnosed at a younger age compared with patients
      with high DAB2 staining. The present study clearly demonstrates that DAB2 is a
      specific marker of the ZG in normal human adrenal glands but that DAB2
      immunostaining is not sufficiently powerful for histopathological diagnosis of
      APA. DAB2 might be involved in excessive aldosterone biosynthesis and correlate
      with specific clinical characteristics of APA patients.

PMID- 28514806
TI  - Human Epicardial Fat Expresses Glucagon-Like Peptide 1 and 2 Receptors Genes.
AB  - Epicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart
      with unique anatomy, functionality, and transcriptome. EAT can serve as a
      therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like
      peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial
      cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2
      receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real
      time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence
      of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects
      with coronary artery disease and type 2 diabetes mellitus undergoing elective
      cardiac surgery. Immunofluorescence was also performed on EAT and SAT samples
      using Mab3f52 against GLP-1R. Our RNA-sequencing (RNA-seq) analysis showed that
      EAT expresses both GLP-1R and GLP-2R genes. qRT-PCR analysis confirmed that GLP
      1R expression was low but detected by 2 different sets of intron-spanning
      primers. GLP-2R expression was detected in all patients and was found to be 5
      fold higher than GLP-1R. The combination of accurately spliced reads from RNA-seq
      and successful amplification using intron-spanning primers indicates that both
      GLP-1R and GLP-2R are expressed in EAT. Immunofluorescence clearly showed that
      GLP-1R is present and more abundant in EAT than SAT. This is the first time that
      human EAT is found to express both GLP-1R and GLP-2R genes. Pharmacologically
      targeting EAT may induce beneficial cardiovascular and metabolic effects.

PMID- 28514807
TI  - Can Transcranial Direct Current Stimulation Modulate Psychophysiological Response
      in Sedentary Men during Vigorous Aerobic Exercise?
AB  - This study evaluated whether transcranial direct current stimulation (tDCS) could
      change physiological and psychological responses during vigorous exercise with a
      constant load. 13 sedentary males (23.0+/-4.2 years; 25.6+/-4.2 kg/m2) took part
      in this randomized, crossed-over, sham-controlled, and double-blinded study.
      Participants underwent 2 sessions with anodal or sham tDCS (2 mA, 20 min) applied
      before exercise over the left temporal cortex targeting the left insular cortex.
      The exercise was performed at vigorous intensity (%HRmax 81.68+/-6.37) for 30
      min. Heart rate (HR), rating of perceived exertion (RPE) and affective responses
      (pleasure/displeasure) were recorded at every 5 min. Additionally, heart rate
      variability (HRV) was measured before, immediately after and 60 min after the end
      of exercise. A 2-way repeated measure ANOVA showed that tDCS improved HRV neither
      at rest nor after exercise (p>0.15). Similarly, HR, RPE, and affective responses
      were not enhanced by tDCS during vigorous exercise (p>0.23). The findings of this
      study suggest that tCDS does not modulate either HRV at rest nor HR, RPE and
      affective responses during exercise. Transcranial direct current stimulation's
      efficiency might depend on the participants' levels of physical fitness and
      parameters of stimulation (e. g., duration, intensity, and arrangement of
      electrodes).

PMID- 28514808
TI  - Physiological Dynamic Apnea Responses in Relation to Apnea Capacity in
      Triathletes.
AB  - The aim was to assess the cardiac, arterial oxygen saturation, lactate, hormonal
      and Borg rating of perceived exertion (RPE) responses to acute apnea in relation
      to apnea capacity in 18 middle-aged triathletes. Subjects were monitored while
      swimming two 50-m freestyle exercise trials with fins at maximal speed: with
      normal frequency breathing (NB) and with complete apnea (Ap); the latter was used
      to assess apnea capacity. The subjects with significant alteration in swimming
      performance inducing a time increase greater than 2.5% during Ap vs. NB were put
      in the group: bad apnea capacity (Bad Ap); the others, who showed no significant
      alteration in performance, were put in the group: Good Ap. Under apnea, both
      groups showed a decrease in arterial oxygen saturation (p<0.05). In Ap
      conditions, only Bad Ap had a significant lower maximal heart rate vs. NB
      (p<0.05), with lower blood lactate (p<0.05) and arm stroke frequency (p<0.01). No
      change in saliva hormonal concentrations was found during the experiment for both
      groups, whereas RPE responses were increased in the Good Ap group under Ap vs. NB
      conditions. In conclusion, a good apnea capacity seems to be associated with
      lower cardiovascular and metabolic apnea alterations in middle-aged
      recreationally-trained triathletes.

PMID- 28514809
TI  - ?
AB  - Whilst Critical Speed (CS) has been successfully translated from the laboratory
      into the field, this translation is still outstanding for the related maximum
      running distance (D'). Using iso-duration exhaustive laboratory and field runs,
      this study investigated the potential interchangeable use of both parameters, D'
      and CS. After an incremental exercise test, 10 male participants (age: 24.9+/-2.1
      yrs; height: 180.8+/-5.8 cm; body mass: 75.3+/-8.6 kg; V VO2peak 52.9+/-3.1
      mL?min-1?kg-1) performed 3 time-to-exhaustion runs on a treadmill followed by 3
      exhaustive time-trial runs on a-400 m athletics outdoor track. Field time-trial
      durations were matched to their respective laboratory time-to-exhaustion runs. D'
      and CS were calculated using the inverse-time model (speed=D'/t+CS). Laboratory
      and field values of D' and CS were not significantly different (221+/-7 m vs.
      225+/-72 m; P=0.73 and 3.75+/-0.36 m?s-1 vs. 3.77+/-0.35 m?s-1, P=0.68), and they
      were significantly correlated (r=0.86 and 0.94). The 95% LoA were +/-75.5 m and
      +/-0.24 m?s-1 for D' and CS, respectively. Applying iso-durations provides non
      significant differences for D' and CS and a significant correlation between
      conditions. This novel translation method can consequently be recommended to
      coaches and practitioners, however a questionable level of agreement indicates to
      use D' with caution.

PMID- 28514810
TI  - Totally Minimally Invasive Esophagectomy and Gastric Pull-Up Reconstruction with
      an Intrathoracic Circular Stapled Anastomosis with a Team of Two (Surgeon and
      Assistant Only).
AB  - Totally minimally invasive esophagectomy (MIE) is nowadays en vogue.1 2 3 4 5
      There are several reports showing that already partial minimally invasive
      esophagectomies (hybrid esophagectomies) with a laparoscopic approach and open
      transthoracic resection are beneficial for patients due to the reduced operative
      trauma. Also for total MIE several groups have reported benefits for patients in
      terms of morbidity and quality of life.1 5 However, different approaches and
      experiences of different esophageal surgery groups are hardly comparable and thus
      do not allow a simple answer in favor of a specific total MIE technique. To
      enlighten the field of total MIE, we present the technique as we perform this
      procedure nearly weekly in our department. The described MIE technique is safe
      and feasible. Changing to this demonstrating technique, we did not have any
      mortality so far, even in the first 30 cases. Especially for surgeons who plan to
      switch from the open surgical technique toward hybrid, MIE or robotic-assisted
      MIE.

PMID- 28514812
TI  - Prevention of Seroconversion after HIV-Infected Needle Stick.

PMID- 28514811
TI  - Reply by the Authors of the Original Article.

PMID- 28514813
TI  - ?

PMID- 28514814
TI  - [Possibilities and Limitations of OCT-Angiography in Patients with Central Serous
      Chorioretinopathy].
AB  - Purpose Central serous chorioretinopathy (CSC) is a commonly acquired maculopathy
      characterized by the accumulation of subretinal fluid at the posterior pole. This
      study aims to analyze optical coherence tomography angiography (OCTA) findings in
      patients with acute and chronic CSC and to compare them to conventional imaging
      methods. Methods A series of 43 consecutive eyes of 29 patients diagnosed with
      CSC and 18 eyes of 9 healthy control subjects were included in this retrospective
      study. The OCTA images were assessed and compared to conventional fluorescence
      (FAG) and indocyanine green angiography (ICG). Results All CSC patients
      demonstrated abnormal areas of focal hypo- and hyperperfusion in the
      choriocapillaris. These were particularly evident in patients with chronic
      atrophic CSC. FAG and ICG imaging revealed leakage points in 10 of 43 eyes and
      choroidal neovascularization (CNV) in 3 of 43 eyes. OCTA imaging confirmed
      leakage points in 4 out of 10 cases and choroidal neovascularization in 2 out of
      3 cases. In one case, OCTA demonstrated a CNV which was not detectable by
      FAG/ICG. Conclusion OCTA reveals areas of focal hypo- and hyperperfusion in the
      choriocapillaris in patients with CSC. Due to the inability to detect plasma
      flow, OCTA is not suitable to detect leakage points in CSC with confidence.
      However, OCTA reliably detects CNV in CSC even in the absence of exudative
      activity and may, therefore, represent an important supplement in the diagnosis
      of CSC.

PMID- 28514815
TI  - [Otto Wichterle and Soft Contact Lenses].

PMID- 28514816
TI  - [Novel Thixotropic Silicone Oils - The Ketchup Bottle Approach for Silicone Oil
      Endotamponades].
AB  - Silicone oil endotamponades need to be injected and removed in a reasonable time
      and under moderate pressure conditions. However, due to ever-decreasing sizes of
      incisions and trocars, injection and removal of highly viscous silicone oils is
      very time-consuming. To address resulting problems like longer treatment times or
      hypotony, thixotropic silicone oils were developed. These oils are characterized
      by a diminished viscosity under constant mechanical stress; whilst there is
      pressure or vacuum acting on it, the oils will become more fluid and, therefore,
      much easier to be applied. Once the force is being removed from the oil, it will
      automatically return to its initial viscosity after a short time.

PMID- 28514817
TI  - [The Role of Intraocular Pressure Fluctuation in the Development and Progression
      of Glaucoma].
AB  - Intraocular pressure fluctuation has been discussed as a risk factor for glaucoma
      development and glaucoma progression. Two clinical trials (Sweden and USA) have
      evaluated the relationship between IOP and glaucoma progression. Both studies
      will be discussed in this review. Additionally, some smaller studies exist that
      are mentioned and discussed as well. This review summarizes the most important
      studies.

PMID- 28514818
TI  - [Diabetes - a Continually Increasing Challenge].

PMID- 28514819
TI  - [39-year-old Woman with Eruptive Skin Lesions on the Face].

PMID- 28514821
TI  - [The Way to Closed Loop - Dream and Reality].
AB  - An old dream of patients with type 1 diabetes and medical teams alike is a fully
      automated insulin therapy. Available sensor-augmented insulin-pumps are able to
      intervene in insulin therapy by reducing the dose. Aim of several studies is to
      add an algorithm to the interaction of pump and sensor, so that insulin doses can
      be regulated fully automatically. Totally closed loop systems are currently not
      yet available for outpatient use. Hybrid closed loop systems have been approved
      in the US. They can improve the metabolic status of patients with type 1
      diabetes. Risks are similar to sensor-augmented insulin-pump therapy. Patients'
      detailed education will continue to be essential for success.

PMID- 28514820
TI  - [Diagnostic Approach to Manifestation of Type 1 Diabetes mellitus].
AB  - The incidence of type 1 and type 2 diabetes mellitus has been increasing
      simultaneously. Formerly, these two patients' populations could be differentiated
      easily, but now, due to the overlapping of both groups, specified diagnostics are
      necessary. In order to substantiate a suspicion on diabetes, quantifying venous
      plasma glucose is the gold standard in diagnostics. As a precaution,
      determination of the HbA1c and OGTT is recommended. It is not necessary to
      determinate antibodies in every new case of diabetes. In patients with a vague
      constellation of clinical picture diagnosis can be ensured by findings of uric
      ketones, BGA, IA-2- and GAD-antibodies and optionally C-peptide. Often T1DM is
      associated with PGAS. Therefore, once manifestation of diabetes is detected,
      screening autoimmune disorders is recommended directly and regularly every two
      years.

PMID- 28514822
TI  - [Cardiovascular Effects of Antidiabetic Therapies].
AB  - Type 2- diabetes mellitus (T2DM) represents a major risk factor for
      cardiovascular complications and mortality. Strict glucose control in the early
      course of the disease prevents cardiovascular complications only in the long run.
      Non-medical therapies (diet, exercise, body weight reduction) bear little
      evidence for positive cardiovascular effects.Bariatric surgery is not number one
      choice in therapy of T2DM. Metformin seems to provide positive cardiovascular
      effects. Insulin seems to be cardiovascular neutral, as well as the DPP4
      inhibitors Saxagliptin, Sitagliptin and Alogliptin. Concerning GLP-1-RAs,
      Lixisenatide has a neutral cardiovascular effect, whereas Liraglutide and
      Semaglutide reduce cardiovascular outcomes. The SGLT2-inhibitor Empagliflozin
      reduces cardiovascular mortality, total mortality and hospitalization by heart
      failure.

PMID- 28514823
TI  - [Fulminant Course of a Clostridium Perfringens Infection with Pathognomonic CT
      finding].
AB  - History and clinical findings A 74-year old woman was accepted by the emergency
      room with severe chest and abdominal pain. She complained about regurgitation
      after ingestion of food followed by sharp pain in her breast. Investigations A
      first examination of the patient showed a tachypnoea und tachycardia up to 122
      beats per minute, the body temperature measured on admission was 38.7  degrees C.
      Due to hemolysis only a few of the requested parameters could be evaluated. CRP
      was increased with 8.32 mg/dl. The hemoglobin dropped from 12.0 g/dl to 10.3 g/dl
      during 4 hours. A computed tomography scan was done because of severe worsening
      of the patient's condition. The CT scan showed two cavities in the right lobe of
      the liver filled with gas. Treatment and course Initial antibiotic therapy with
      Ceftriaxon was immediately started. During her stay in the emergency room the
      patient showed a severe worsening of her condition. Therefore a CT scan was
      initiated after the abdominal ultrasound revealed nothing specific. During the CT
      examination the patient stopped breathing sufficiently, followed by hematuria and
      vomiting a large amount of blood. The patient died 8.5 hours of an irreversible
      cardiovascular failure after admission to the hospital. Conclusion A rapid
      decline of the patient's condition in addition to hemolysis and a gas-filled
      liver necrosis are pathognomonic signs for an infection with clostridium
      perfringens which requires immediate treatment. Only an immediate surgical
      intervention in combination with an adapted antibiotic increases chances of
      survival in patients with clostridia.

PMID- 28514825
TI  - [The Pulmonary Vein Isolation is the Primary Therapy for Paroxysmal Atrial
      Fibrillation].

PMID- 28514824
TI  - [Attaching an Insulin Pump].

PMID- 28514826
TI  - [Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation is - Still - not a
      Primary Therapy of Paroxysmal Atrial Fibrillation].

PMID- 28514827
TI  - ?

PMID- 28514828
TI  - ?

PMID- 28514829
TI  - Does Hofstetter's equation predict the real amplitude of accommodation in
      children?
AB  - PURPOSE: The aim was to determine the distribution and associated factors of
      accommodative amplitude (AA) in six- to 12-year-old children and compare the
      results with those calculated using Hofstetter's formula. METHODS: In a cross
      sectional study in 2015, random sampling was done from urban and rural
      populations of Shahroud, northern Iran. Participating schoolchildren were
      examined for manifest, cycloplegic and subjective refraction, as well as
      uncorrected vision and visual acuity. The AA was measured with Donders' push-up
      method using a ruler. The near point of convergence (NPC) was also measured.
      RESULTS: Of the 6,624 selected children, 5,620 participated in the study and
      after applying the exclusion criteria, the final analyses were done on data from
      5,444 schoolchildren. The mean age of the final sample was 9.24 +/- 1.71 years
      (from six to 12 years) and 53.6 per cent (n = 2,919) were boys. Mean measured AA
      was 14.44 D (95 per cent confidence interval [CI]: 14.33-14.55). In all age
      groups, the mean measured AA was less than the predicted mean value calculated
      with the Hofstetter's equation. Mean measured AA was 14.44 D (95 per cent CI:
      14.28-14.59) and 14.45 D (95 per cent CI: 14.29-14.6) in boys and girls,
      respectively (p = 0.926). AA significantly declined with age (coefficient: -0.18,
      95 per cent CI: -0.23 to -0.12, p < 0.001). Mean AA in emmetropic, myopic and
      hyperopic children was 14.31 D, 17.30 D and 14.87 D, respectively. Older age
      (coefficient = -0.18), living in rural areas (coefficient = -0.48) and NPC
      (coefficient = 0.47) inversely related with AA and higher AA was associated with
      a shift of the spherical equivalent refraction toward myopia (coefficient = 
      0.41). CONCLUSION: The differences among groups with different types of
      refractive error and high AA in children with myopia are important findings of
      this study. The results of the present study suggest that Hofstetter's formula
      provides inaccurate AA estimates in children and thus, the interpretation of this
      index requires further population-based studies in different racial and ethnic
      groups.

PMID- 28514830
TI  - Association of maternal serum PAPP-A levels, nuchal translucency and crown-rump
      length in first trimester with adverse pregnancy outcomes: retrospective cohort
      study.
AB  - OBJECTIVE: Are first trimester serum pregnancy-associated plasma protein-A (PAPP
      A), nuchal translucency (NT) and crown-rump length (CRL) prognostic factors for
      adverse pregnancy outcomes? METHOD: Retrospective cohort, women, singleton
      pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression.
      OUTCOMES: small for gestational age (SGA), pre-eclampsia (PE), preterm birth
      (PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND).
      RESULTS: A total of 12 592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824
      (14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths
      (0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted
      odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91
      (95% CI 0.85,0.97)] and stillbirth [0.71 (95% CI 0.52,0.98)] as PAPP-A increases.
      Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage
      [aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as
      CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three
      factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b)
      PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. CONCLUSIONS:
      Pregnancy-associated plasma protein-A, NT and CRL are independent prognostic
      factors for adverse pregnancy outcomes, particularly PAPP-A and SGA with lower
      PAPP-A associated with increased risk. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28514833
TI  - Antinociceptive effect of (-)-alpha-bisabolol in nanocapsules.
AB  - This study aimed to develop and to evaluate the antinociceptive effect of a drug
      delivery system containing (-)-alpha-bisabolol (BISA). Nanocapsules containing
      BISA (BISA-NC) were prepared using acetylated galatomannan. Particle size
      distribution was determined by atomic force microscopy, zeta potential
      measurement and photon correlation spectroscopy. Corneal nociception was induced
      by topical application of 5M NaCl and the nociceptive behavior was characterized
      by eye wiping in mice. Molecular docking was conducted on the TRPV1 channel.
      Nanocapsules showed mean particle sizes between 94.44 and 105.44nm and the zeta
      potential of was -1.34mV. Animals pretreated with BISA-NC (200mg/mL) had a
      significant reduction (**p<0.01) in the number of nociceptive behaviors. Docking
      study indicated an interaction between BISA and TRPV1. This study indicates that
      BISA-NC may be useful for producing eye drops for the treatment of ocular pain.

PMID- 28514831
TI  - Hypericum perforatum extract attenuates behavioral, biochemical, and
      neurochemical abnormalities in Aluminum chloride-induced Alzheimer's disease
      rats.
AB  - Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative
      diseases. Aluminum, a neurotoxic metal, is considered as the pathological
      hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a
      neuroprotective agent that can prevent neurodegenerative pathologies through
      antioxidants, anti-inflammatory and regulating neurotransmitter release in animal
      model of neuropathy. The present study aimed to identify the potential
      neuroprotective of HPE on AlCl3-induced AD rats. Rats were treated with AlCl3 for
      90days to induce behavioral, biochemical, and neurochemical similar to AD. From
      31thday, the rats were treated with HPE for 60days. Our results showed HPE
      improved cognitive function in AlCl3-induced AD rats, and attenuated AlCl3
      induced increase in acetylcholinesterase activity and glutamic acid level as well
      as decreased in noradrenaline and dopamine level. In addition, HPE reversed AlCl3
      induced hippocampal pathology including amyloid-beta (Abeta) accumulation
      (elevated Abeta42 level and amyloid plaques), oxidative stress (increased
      reactive oxygen species level and thiobarbituric acid reactive substances level,
      decreased glutathione level and superoxide dismutase activity) and
      neuroinflammatory (increased mRNA expressions of Interleukin-1beta, Interleukin
      6, Tumor necrosis factor-alpha and major histocompatibility complex class II) in
      hippocampus of rats. Thus, HPE is conferred neuroprotection against AlCl3-induced
      AD like pathology.

PMID- 28514832
TI  - Anti-obesity effects of tea from Mangifera indica L. leaves of the Uba variety in
      high-fat diet-induced obese rats.
AB  - Due to the high content of bioactive compounds, herbal teas are being
      investigated as adjuvant in chronic disease management. Studies have shown that
      mango leaf tea contain mangiferin, total phenolics and antioxidants, compounds
      with many functional properties. Therefore, this study aims to evaluate the anti
      obesity effects of tea from Mangifera indica L. leaves, Uba variety (TML), in
      obese rats fed a high-fat diet (HFD). For this, adult male Wistar rats were
      divided into three groups (n=8): the control group (fed AIN-93 diet), obese group
      (fed a HFD) and treated group (fed a HFD and supplemented with TML for 8 weeks).
      We analysed biometric measures and serum biochemical parameters of metabolic
      control, inflammation and oxidative stress biomarkers, histomorphometry of
      visceral adipose tissue and mRNA expression of peroxisome proliferator-activated
      receptor gamma co-activator 1 alpha (PPAR-gamma), lipoprotein lipase (LPL) and
      fatty acid synthase (FAS). The consumption of TML (24.7+/-2.1mL/day) exerted
      antioxidant and anti-inflammatory effects, increasing total antioxidant capacity
      and interleukin-10 serum concentrations, reduced abdominal fat accumulation,
      upregulated PPAR-gamma and LPL and downregulated FAS expression. Our data suggest
      that TML has therapeutic potential in treating obesity and related diseases
      through regulating the expression of transcriptional factors and enzymes
      associated with adipogenesis.

PMID- 28514834
TI  - Antitumor activity of Brazilian red propolis fractions against Hep-2 cancer cell
      line.
AB  - Continuous increases in the rates of tumor diseases have highlighted the need for
      identification of novel and inexpensive antitumor agents from natural sources. In
      this study, we investigated the effects of enriched fraction from hydroalcoholic
      Brazilian red propolis extract against Hep-2 cancer cell line. Initially 201
      fractions were arranged in 12 groups according to their chromatographic
      characteristics (A-L). After an in vitro cell viability screening, J and L were
      further selected as promising enriched fractions for this study. The chemical
      characterization was performed and Biochanin A, Formononetin, and Liquiritigenin
      compounds were quantified. Through MTT viability assay and morphological changes
      observed by Giemsa and DAPI staining, the results showed that red propolis
      inhibited cancer cells growth. Flow cytometry results indicated effects that were
      partly mediated through programmed cell death as confirmed by externalization of
      phosphatidylserine, DNA cleaved assay, increase at SUB G1-G0 phase in cell cycle
      analysis and loss of mitochondrial membrane potential. In conclusion, our results
      demonstrated that red propolis enriched fractions promoted apoptotic effects in
      human cancer cells through the mechanisms involving mitochondrial perturbation.
      Therefore, red propolis fractions contain candidate agents for adjuvant cancer
      treatment, which further studies should elucidate the comprehensive mechanistic
      pathways.

PMID- 28514835
TI  - Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose
      diet-treated rats.
AB  - Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for
      alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism
      was not clearly understood. This study was designed to determine the effect of
      genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley
      rats were divided into 4 groups: the control group, high fat-high sucrose diet
      (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body
      weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver
      histopathological examination were characterized. The protein levels of liver AMP
      activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA
      carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element
      binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of
      fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT),
      peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyl
      transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse
      transcription polymerase chain reaction (RT-PCR). Results showed that genistein
      effectively improved serum and hepatic lipid metabolism and diminished fat
      accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were
      increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of
      FAS and GPAT were lower, but PPARalpha, CPT-1, ACO were higher in rats treated
      with genistein compared with HFS group. Collectively, genistein can improve
      hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and
      inhibiting lipid synthesis in liver.

PMID- 28514836
TI  - Oxidation of organic contaminant in a self-driven electro/natural
      maghemite/peroxydisulfate system: Efficiency and mechanism.
AB  - Electro-assisted iron-mediated persulfate (PS) activation process has been
      successfully employed to oxidize organic contaminant. However, a majority of iron
      based catalysts used for PS activation was synthesized through complicated or
      demanding procedures and may have potential risks on environment during the
      preparation process. Herein, natural maghemite (NM) which is abundant on the
      earth was employed to activate peroxydisulfate (PDS) in an electrolytic cell. The
      voltage was provided by microbial fuel cell (MFC) instead of external power as
      reported in the previous studies, so as to establish a self-driven
      electro/natural maghemite/PDS system (MFC/NM/PDS) for the oxidation of acid
      orange 7 (AO7). The results showed that above 90% removal efficiency of AO7 was
      achieved in a wide range of pH (3.0-9.0) after 100min reaction. Singlet oxygen
      was identified for the first time during PDS activation and surface bound sulfate
      radicals served as the dominant active species responsible for AO7 oxidation. The
      underlying mechanism of AO7 elimination in the MFC/NM/PDS system was elucidated
      through quenching tests, electron paramagnetic resonance (EPR) and X-ray
      photoelectron spectroscopy (XPS) techniques. The variation of TOC and
      cytotoxicity to Escherichia coli was explored. The intermediate products formed
      were identified using LC-TOF-MS technique and a possible pathway of AO7
      degradation was proposed.

PMID- 28514837
TI  - Decomposing an urban soundscape to reveal patterns and drivers of variation in
      anthropogenic noise.
AB  - Continuous and intermittent noise may have different effects on humans and
      wildlife, therefore distinguishing temporal patterns of noise and their drivers
      is important for policy regarding both public health and wildlife management. We
      visualized patterns and explored land-use drivers of continuous and high
      amplitude intermittent sound pressure levels (SPLs) on an urban campus in
      Michigan, U.S.A. To visualize patterns of SPLs, we introduce decibel duration
      curves (DDCs), which show the cumulative frequency distribution of SPLs and aid
      in the interpretation of statistical SPLs (Ln values) that reflect continuous
      versus intermittent sounds. DDCs and Ln values reveal that our 24 recording
      locations varied in the intensity of both continuous and intermittent noise, with
      intermittent high-amplitude sound events in particular contributing to
      variability in SPLs over the study site. Time of day influenced both continuous
      and intermittent SPLs, as locations relatively close to manmade structures
      (buildings, roads and parking lots) experienced higher SPLs as the day
      progressed. Continuous SPLs increased with decreasing distance to manmade
      structures, whereas intermittent SPLs increased with decreasing distance to roads
      and increasing distance to buildings. Thus, different land-use factors influenced
      patterns of continuous and intermittent noise, which suggests that different
      policy and strategies may be needed to ameliorate their effects on the public and
      wildlife.

PMID- 28514838
TI  - Macroinvertebrate short-term responses to flow variation and oxygen depletion: A
      mesocosm approach.
AB  - In Mediterranean rivers, water scarcity is a key stressor with direct and
      indirect effects on other stressors, such as water quality decline and inherent
      oxygen depletion associated with pollutants inputs. Yet, predicting the responses
      of macroinvertebrates to these stressors combination is quite challenging due to
      the reduced available information, especially if biotic and abiotic seasonal
      variations are taken under consideration. This study focused on the response of
      macroinvertebrates by drift to single and combined effects of water scarcity and
      dissolved oxygen (DO) depletion over two seasons (winter and spring). A factorial
      design of two flow velocity levels - regular and low (vL) - with three levels of
      oxygen depletion - normoxia, medium depletion (dM) and higher depletion (dH) -
      was carried out in a 5-artificial channels system, in short-term experiments.
      Results showed that both stressors individually and together had a significant
      effect on macroinvertebrate drift ratio for both seasons. Single stressor effects
      showed that macroinvertebrate drift decreased with flow velocity reduction and
      increased with DO depletion, in both winter and spring experiments. Despite
      single stressors opposing effects in drift ratio, combined stressors interaction
      (vL*dM and vL*dH) induced a positive synergistic drift effect for both seasons,
      but only in winter the drift ratio was different between the levels of DO
      depletion. Stressors interaction in winter seemed to intensify drift response
      when reached lower oxygen saturation. Also, drift patterns were different between
      seasons for all treatments, which may depend on individual's life stage and
      seasonal behaviour. Water scarcity seems to exacerbate the oxygen depletion
      conditions resulting into a greater drifting of invertebrates. The potential
      effects of oxygen depletion should be evaluated when addressing the impacts of
      water scarcity on river ecosystems, since flow reductions will likely contribute
      to a higher oxygen deficit, particularly in Mediterranean rivers.

PMID- 28514839
TI  - Occurrence of brominated dioxins in a study using various firefighting methods.
AB  - The use of different firefighting methods influences how fast a fire is
      extinguished and how fast the temperature drops in the area affected by the fire.
      These differences may also influence the formation of harmful pollutants during
      firefighting of an accidental fire. The aim was to study occurrence of brominated
      dibenzo-p-dioxins and furans (PBDD/Fs) in gas and soot during five fire scenarios
      resembling a small apartment fire and where different firefighting methods were
      used. Samples of gas and soot were taken both during the buildup of the fire and
      during the subsequent extinguishing of the fire while using different
      firefighting methods (nozzle, compressed air foam system, cutting extinguisher)
      and an extinguishing additive. New containers equipped with identical sets of
      combustible material were used for the five tests. The use of different
      firefighting methods and extinguishing additive induced variations in
      concentration and congener profiles of detected PBDD/Fs. The concentration range
      of ?PBDD/Fs in gas was 4020-18,700pg/m3, and in soot 76-4092pg/m2. PBDFs were the
      predominant congeners and 1,2,3,4,6,7,8-HpBDF was the most abundant congener.
      Chlorinated dibenzo-p-dioxins and furans (PCDD/Fs) were also monitored. The
      PBDD/Fs contributed with in average 97% to the total (PCDD/Fs plus PBDD/Fs) toxic
      equivalents, in soot and gas. During extinguishing, the shorter time the
      temperature was around 300 degrees C, the lower occurrence of PBDD/Fs. In the
      study the firefighting methods showed a difference in how effectively they
      induced a temperature decrease below 300 degrees C in the fire zone during
      quenching, where cutting extinguishing using additive and the compressed air foam
      system showed the fastest drop in temperature.

PMID- 28514840
TI  - Plastics in the North Atlantic garbage patch: A boat-microbe for hitchhikers and
      plastic degraders.
AB  - Plastic is a broad name given to different polymers with high molecular weight
      that impact wildlife. Their fragmentation leads to a continuum of debris sizes
      (meso to microplastics) entrapped in gyres and colonized by microorganisms. In
      the present work, the structure of eukaryotes, bacteria and Archaea was studied
      by a metabarcoding approach, and statistical analysis associated with network
      building was used to define a core microbiome at the plastic surface. Most of the
      bacteria significantly associated with the plastic waste originated from non
      marine ecosystems, and numerous species can be considered as hitchhikers, whereas
      others act as keystone species (e.g., Rhodobacterales, Rhizobiales,
      Streptomycetales and Cyanobacteria) in the biofilm. The chemical analysis
      provides evidence for a specific colonization of the polymers.
      Alphaproteobacteria and Gammaproteobacteria significantly dominated mesoplastics
      consisting of poly(ethylene terephthalate) and polystyrene. Polyethylene was also
      dominated by these bacterial classes and Actinobacteria. Microplastics were made
      of polyethylene but differed in their crystallinity, and the majorities were
      colonized by Betaproteobacteria. Our study indicated that the bacteria inhabiting
      plastics harboured distinct metabolisms from those present in the surrounding
      water. For instance, the metabolic pathway involved in xenobiotic degradation was
      overrepresented on the plastic surface.

PMID- 28514841
TI  - Endoscopic Management of Pancreatic Fluid Collections in Children.
AB  - The incidence of acute pancreatitis in children has increased over the last few
      decades. The development of pancreatic fluid collection is not uncommon after
      severe acute pancreatitis, although its natural course in children and
      adolescents is poorly understood. Asymptomatic fluid collections can be safely
      observed without any intervention. However, the presence of clinically
      significant symptoms warrants the drainage of these fluid collections. Endoscopic
      management of pancreatic fluid collection is safe and effective in adults. The
      use of endoscopic ultrasound (EUS)-guided procedure has improved the efficacy and
      safety of drainage of pancreatic fluid collections, which have not been well
      studied in pediatric populations, barring a scant volume of small case series.
      Excellent results of EUS-guided drainage in adult patients also need to be
      verified in children and adolescents. Endoprostheses used to drain pancreatic
      fluid collections include plastic and metal stents. Metal stents have wider
      lumens and become clogged less often than plastic stents. Fully covered metal
      stents specifically designed for pancreatic fluid collection are available, and
      initial studies have shown encouraging results in adult patients. The future of
      endoscopic management of pancreatic fluid collection in children appears
      promising. Prospective studies with larger sample sizes are required to establish
      their definitive role in the pediatric age group.

PMID- 28514842
TI  - Gender difference in radiotherapy-induced carotid stenosis.
AB  - Radiotherapy (RT) is often the first choice of treatment for cancer of the
      larynx. Studies have shown that the incidence of carotid stenosis (CS) after
      radiotherapy of laryngeal cancer is increasing, and that gender difference in
      radiotherapy-induced side effects exist. Thus, we examined the gender difference
      in the incidence of CS and the impact of microinflammatory factors after
      radiotherapy. We reported this study on patients who received radiotherapy as
      part of the treatment for laryngeal cancer in the Jilin Province in China. One
      hundred sixty-four males and 152 females were treated with radiotherapy between
      2006 and 2016. The carotid diameter was determined by measuring carotid intima
      media thickness in the common, external and internal carotid artery.
      Microinflammatory conditions were assessed by measuring the level of high
      sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha). Other studied risk factors included age, treatment
      modalities, radiation dose and energy, the height of the radiation field, and the
      follow-up time. CS was detected in 161 (50.9%) of the 316 patients. Carotid
      stenosis was mainly clinically unsuspected, two patients had anamnesis of
      unconsciousness. Importantly, fewer women (36.1%) had CS than men (64.6%)
      (p=0.004). Furthermore, male patients showed higher serum levels of hs-CRP, IL-6,
      and TNF-alpha. Taken together, our study suggested that women underoing
      radiotherapy of laryngeal cancer are less likely to have CS than men. Therefore,
      routine assessment after irradiation of laryngeal cancer seems necessary for
      clinical detection of asymptomatic CS, particularly in male patients.

PMID- 28514843
TI  - Single-Cell Real-Time Visualization and Quantification of Perylene
      Bioaccumulation in Microorganisms.
AB  - Bioaccumulation of perylene in Escherichia coli and Staphylococcus aureus was
      visualized and quantified in real time with high sensitivity at high temporal
      resolution. For the first time, single-molecule fluorescence microscopy (SMFM)
      with a microfluidic flow chamber and temperature control has enabled us to record
      the dynamic process of perylene bioaccumulation in single bacterial cells and
      examine the cell-to-cell heterogeneity. Although with identical genomes,
      individual E. coli cells exhibited a high degree of heterogeneity in perylene
      accumulation dynamics, as shown by the high coefficient of variation (C.V =
      1.40). This remarkable heterogeneity was exhibited only in live E. coli cells.
      However, the bioaccumulation of perylene in live and dead S. aureus cells showed
      similar patterns with a low degree of heterogeneity (C.V = 0.36). We found that
      the efflux systems associated with Tol C played an essential role in perylene
      bioaccumulation in E. coli, which caused a significantly lower accumulation and a
      high cell-to-cell heterogeneity. In comparison with E. coli, the Gram-positive
      bacteria S. aureus lacked an efficient efflux system against perylene. Therefore,
      perylene bioaccumulation in S. aureus was simply a passive diffusion process
      across the cell membrane.

PMID- 28514844
TI  - Measurement of the 30Si Mole Fraction in the New Avogadro Silicon Material by
      Neutron Activation and High-Resolution gamma-Spectrometry.
AB  - The use of new silicon single crystals highly enriched in 28Si recently produced
      for the upcoming redetermination of the Avogadro constant requires knowledge of
      their molar masses. The isotopic composition data are collected independently in
      different laboratories but all using the virtual element technique with
      multicollector inductively coupled plasma mass spectrometers. In this framework,
      the comparison of the results with an independent measurement of the amount of at
      least one of the depleted isotopes is useful to limit hidden systematic errors.
      To this aim, the 30Si mole fraction of a sample of the new material was measured
      using a relative measurement protocol based on instrumental neutron activation
      analysis. The protocol is similar to that previously applied with the AVO28
      silicon material used for the last determination of the Avogadro constant value
      with the exception that unknown and standard samples are not coirradiated. The
      x(30Si) = 5.701 * 10-7 mol mol-1 estimate is close to the expected one and is
      given with a standard uncertainty of 8.8 * 10-9 mol mol-1. This value, if
      adopted, gives a contribution to the relative standard uncertainty of the
      Avogadro constant of 6.3 * 10-10.

PMID- 28514845
TI  - In Vivo Mercury Demethylation in a Marine Fish (Acanthopagrus schlegeli).
AB  - Mercury (Hg) in fish has attracted public attention for decades, and
      methylmercury (MeHg) is the predominant form in fish. However, the in vivo MeHg
      demethylation and its influence on Hg level in fish have not been well-addressed.
      The present study investigated the in vivo demethylation process in a marine fish
      (black seabream, Acanthopagrus schlegeli) under dietary MeHg exposure and
      depuration and quantified the biotransformation and interorgan transportation of
      MeHg by developing a physiologically based pharmacokinetic (PBPK) model. After
      exposure, we observed a 2-fold increase of the whole-body inorganic Hg (IHg),
      indicating the existence of an in vivo demethylation process. The results
      strongly suggested that the intestine played a predominant role in MeHg
      demethylation with a significant rate (6.6 +/- 1.7 day-1) during exposure,
      whereas the hepatic demethylation appeared to be an extremely slow (0.011 +/-
      0.001 day-1) process and could hardly affect the whole-fish Hg level. Moreover,
      demethylation in the intestine served as an important pathway for MeHg
      detoxification. Our study also pointed out that in vivo MeHg demethylation could
      influence Hg level and speciation in fish although food is the major pathway for
      Hg accumulation. Enhancing in vivo MeHg biotransformation (especially in the
      intestine) could be a potential key solution in minimizing Hg contamination in
      fish. The related factors involved in intestinal demethylation deserve more
      attention in the future.

PMID- 28514846
TI  - Natural Mutagenesis-Enabled Global Proteomic Study of Metabolic and Carbon Source
      Implications in Mutant Thermoacidophillic Archaeon Sulfolobus solfataricus
      PBL2025.
AB  - The thermoacidophilic crenarchaeon Sulfolobus solfataricus has been widely used
      as a model organism for archaeal systems biology research. Investigation using
      its spontaneous mutant PBL2025 provides an effective metabolic baseline to study
      subsequent mutagenesis-induced functional process shifts as well as changes in
      feedback inhibitions. Here, an untargeted metabolic investigation using
      quantitative proteomics and metabolomics was performed to correlate changes in S.
      solfataricus strains P2 against PBL2025 and under both glucose and tryptone. The
      study is combined with pathway enrichment analysis to identify prominent proteins
      with differential stoichiometry. Proteome level quantification reveals that over
      20% of the observed overlapping proteome is differentially expressed under these
      conditions. Metabolic-induced differential expressions are observed along the
      central carbon metabolism, along with 12 other significantly regulated pathways.
      Current findings suggest that PBL2025 is able to compensate through the induction
      of carbon metabolism, as well as other anabolic pathways such as Val, Leu and iso
      Leu biosynthesis. Studying protein abundance changes after changes in carbon
      sources also reveals distinct differences in metabolic strategies employed by
      both strains, whereby a clear down-regulation of carbohydrate and nucleotide
      metabolism is observed for P2, while a mixed response through down-regulation of
      energy formation and up-regulation of glycolysis is observed for PBL2025. This
      study contributes, to date, the most comprehensive network of changes in
      carbohydrate and amino acid pathways using the complementary systems biology
      observations at the protein and metabolite levels. Current findings provide a
      unique insight into molecular processing changes through natural (spontaneous)
      metabolic rewiring, as well as a systems biology understanding of the metabolic
      elasticity of thermoacidophiles to environmental carbon source change,
      potentially guiding more efficient directed mutagenesis in archaea.

PMID- 28514847
TI  - Electric-Field Assisted Assembly of Colloidal Particles into Ordered Nonclose
      Packed Arrays.
AB  - Nonclose-packed colloidal arrays have many potential applications ranging from
      plasmonic sensors, light trapping for photovoltaics, to transparent electrodes.
      However, scalable fabrication of those structures remains a challenge. In this
      Article, we investigate the robustness of an electric-field assisted approach
      systematically. A monolayer of nonclose-packed crystalline array is first created
      under a low-frequency alternating-current electric field in solution. We then
      apply a sequence of direct-current pulses to fix the particle array onto the
      substrate so that it remains intact even after both field removal and solvent
      evaporation. Key process parameters such as the alternating-current field
      strength, direct-current magnitude, particle concentration, and solvent
      evaporation rate that affect both ordering and fixing of colloidal particles have
      been studied systematically. We find that direct currents with an intermediate
      magnitude induce electrophoretic motion of particles toward the substrate and
      facilitate their permanent adhesion on the substrate due to strong van der Waals
      attraction. A higher current, however, causes lateral aggregation of particles
      arising from electroosmotic flow of solvent and destroys the periodic ordering
      between particles. This approach, in principle, can be conveniently adapted into
      the continuous convective assembly process, thus making the fabrication of
      nonclose-packed colloidal arrays scalable.

PMID- 28514848
TI  - Structure and Oxidation of Pyrrole Adducts Formed between Aflatoxin B2a and
      Biological Amines.
AB  - Aflatoxin B2a has been shown to bind to proteins through a dialdehyde
      intermediate under physiological conditions. The proposed structure of this
      adduct has been published showing a Schiff base interaction, but adequate
      verification using structural elucidation instrumental techniques has not been
      performed. In this work, we synthesized the aflatoxin B2a amino acid adduct under
      alkaline conditions, and the formation of a new product was determined using high
      performance liquid chromatography-time-of-flight mass spectrometry. The resulting
      accurate mass was used to generate a novel proposed chemical structure of the
      adduct in which the dialdehyde forms a pyrrole ring with primary amines rather
      than the previously proposed Schiff base interaction. The pyrrole structure was
      confirmed using 1H, 13C, correlation spectroscopy, heteronuclear single quantum
      correlation, and heteronuclear multiple bond correlation NMR and tandem mass
      spectrometry. Reaction kinetics show that the reaction is overall second order
      and that the rate increases as pH increases. Additionally, this study shows for
      the first time that aflatoxin B2a dialdehyde forms adducts with
      phosphatidylethanolamines and does so through pyrrole ring formation, which makes
      it the first aflatoxin-lipid adduct to be structurally identified. Furthermore,
      oxidation of the pyrrole adduct produced a product that was 16 m/z heavier. When
      the aflatoxin B2a-lysine (epsilon) adduct was oxidized, it gave a product with an
      accurate mass, mass fragmentation pattern, and 1H NMR spectrum that match
      aflatoxin B1-lysine, which suggest the transformation of the pyrrole ring to a
      pyrrolin-2-one ring. These data give new insight into the fate and chemical
      properties of biological adducts formed from aflatoxin B2a as well as possible
      interferences with known aflatoxin B1 exposure biomarkers.

PMID- 28514850
TI  - DNA Dendrimer-Streptavidin Nanocomplex: an Efficient Signal Amplifier for
      Construction of Biosensing Platforms.
AB  - We develop a DNA dendrimer-streptavidin (SA) nanocomplex as a novel signal
      amplifier to create biosensing platforms for disease-related species. The DNA
      dendrimer-SA nanocomplex is fabricated by cross-linking the nonlinear
      hybridization chain reaction based DNA dendrimer with the SA-coupled linker DNA
      and possesses multiple sticky ends, a high molecular weight, and a hyperbranched
      nanostructure with large numbers of DNA duplexes. Taking advantage of the DNA
      dendrimer-SA nanocomplex and a label-free quartz crystal microbalance (QCM)
      technology, we first construct a mass-sensitive QCM biosensing platform for
      nucleic acids, which displays high selectivity and sensitivity, with a detection
      limit of 0.062 nM KRAS gene fragment. Then we present a fluorescent sensing
      strategy toward HeLa cells by functionalizing the DNA dendrimer-SA nanocomplex
      using the sgc8 aptamer and the SYBR Green I intercalating dye. The spiked
      recoveries of targets in physiological media are greater than 90%, demonstrating
      potential application of created biosensing platforms in clinical diagnosis. This
      work expands the rule set of designing DNA nanomaterials for development of
      biosensing strategies, and provides universal platforms for detecting disease
      related species through simply altering the related capture and reporter DNA
      sequences.

PMID- 28514851
TI  - Blood-Brain Barrier Penetrating Biologic TNF-alpha Inhibitor for Alzheimer's
      Disease.
AB  - Tumor necrosis factor alpha (TNF-alpha) driven processes are involved at multiple
      stages of Alzheimer's disease (AD) pathophysiology and disease progression.
      Biologic TNF-alpha inhibitors (TNFIs) are the most potent class of TNFIs but
      cannot be developed for AD since these macromolecules do not cross the blood
      brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the
      extracellular domain of the type II human TNF receptor (TNFR) to a chimeric
      monoclonal antibody (mAb) against the mouse transferrin receptor (TfR),
      designated as the cTfRMAb-TNFR fusion protein. The cTfRMAb domain functions as a
      molecular Trojan horse, binding to the mouse TfR and ferrying the biologic TNFI
      across the BBB via receptor-mediated transcytosis. The aim of the study was to
      examine the effect of this BBB-penetrating biologic TNFI in a mouse model of AD.
      Six-month-old APPswe, PSEN 1dE9 (APP/PS1) transgenic mice were treated with
      saline (n = 13), the cTfRMAb-TNFR fusion protein (n = 12), or etanercept (non-BBB
      penetrating biologic TNFI; n = 11) 3 days per week intraperitoneally. After 12
      weeks of treatment, recognition memory was assessed using the novel object
      recognition task, mice were sacrificed, and brains were assessed for amyloid beta
      (Abeta) load, neuroinflammation, BBB damage, and cerebral microhemorrhages. The
      cTfRMAb-TNFR fusion protein caused a significant reduction in brain Abeta burden
      (both Abeta peptide and plaque), neuroinflammatory marker ICAM-1, and a BBB
      disruption marker, parenchymal IgG, and improved recognition memory in the
      APP/PS1 mice. Fusion protein treatment resulted in low antidrug-antibody
      formation with no signs of either immune reaction or cerebral microhemorrhage
      development with chronic 12-week treatment. Chronic treatment with the cTfRMAb
      TNFR fusion protein, a BBB-penetrating biologic TNFI, offers therapeutic benefits
      by targeting Abeta pathology, neuroinflammation, and BBB-disruption, overall
      improving recognition memory in a transgenic mouse model of AD.

PMID- 28514849
TI  - Intramolecular Hydrogen Atom Transfer in Aminyl Radical at Room Temperature with
      Large Kinetic Isotope Effect.
AB  - We report a large kinetic isotope effect at 298 K, kH/kD ~ 150, associated with
      an intramolecular 1,5-hydrogen atom transfer (1,5-HAT) in the decay of a
      PEGylated carbazyl (aminyl) radical in solution. The experimental observations
      surprisingly combine the hallmarks of tunneling, including large KIEs and unusual
      activation parameters, with linear Arrhenius and Eyring plots over an
      exceptionally wide temperature range of 116 K.

PMID- 28514852
TI  - Separated Immobilization of Incompatible Enzymes on Polymer Substrate via Visible
      Light Induced Living Photografting Polymerization.
AB  - The use of the mixed catalytic system with several enzymes can provide multiple
      benefits in terms of the cost, simplification of a multistep reaction, and
      effectiveness of complex chemical reactions. Although study of different enzyme
      coimmobilization systems has attracted increasing attention in recent years,
      separately immobilizing enzymes which can not coexist on one support is still one
      of the great challenges. In this paper, a simple and effective strategy was
      introduced to separately encapsulate incompatible trypsin and transglutaminase
      (TGase) into different poly(ethylene glycol) (PEG) network layer grafted on low
      density polyethylene (LDPE) film via visible light induced living photografting
      polymerization. As a proof of concept, this dual-enzyme separately loaded film
      was used to catalyze the synthesis of a new target antitumor drug LTV
      azacytidine. The final results demonstrated that this strategy could maintain
      higher activities of both enzymes than the mixed coimmobilization method. And the
      mass spectra analysis results demonstrated that LTV-azacytidine was successfully
      synthesized. We believe that this facile and mild separately immobilizing
      incompatible enzyme strategy has great application potential in the field of
      biocatalysis.

PMID- 28514853
TI  - Targeting the Central Nervous System (CNS): A Review of Rabies Virus-Targeting
      Strategies.
AB  - The transport of drugs across the blood-brain barrier is challenging. The use of
      peptide sequences derived from viruses with a central nervous system (CNS)
      tropism is one elegant option. A prominent example is the rabies virus
      glycopeptide-29 (RVG-29), which is said to enable a targeted brain delivery.
      Although the entry mechanism of the rabies virus into the CNS is very well
      characterized, it is unknown whether RVG-29-functionalized drug delivery systems
      (DDSs) follow this pathway. RVG-29-functionalized DDSs present themselves with
      modifications of the RVG-29 peptide sequence and different physicochemical
      properties compared to the rabies virus. To our surprise, the impact of these
      changes on the functionality is completely neglected. This review explores virus
      related CNS-targeting strategies by comparing RVG-29-functionalized DDSs with
      regard to their peptide modification, physiochemical properties and their
      behavior in cell culture studies with a special focus on the original pathway of
      rabies virus entry into the CNS.

PMID- 28514854
TI  - New Approach for the Synthesis of Nanozirconia Fortified Microcapsules.
AB  - Robust poly(urea-formaldehyde) (PUF) microcapsules with composite shells
      comprising zirconia (ZrO2) nanopowder incorporated in PUF were fabricated via a
      novel and facile one-pot synthesis. ZrO2 nanopowder was chosen because it owns
      one of the highest mechanical strengths among ceramics. The nanopowder was
      predispersed in the core material to combine encapsulation and fortification into
      a single process. In the core, the well-dispersed nanopowder migrated to the
      interface, where PUF polymerization took place. The mechanical strength of the
      microcapsule with nano-ZrO2 incorporated in the shell (42% by weight) is three
      times greater than that of the microcapsule without ZrO2. In a preliminary
      application wherein the microcapsules were embedded in a model of poly(vinyl
      alcohol) (PVA) membrane, the PVA specimen exhibited a higher ultimate tensile
      strength when fortified microcapsules were embedded than when unfortified
      microcapsules were used.

PMID- 28514855
TI  - Osmotic Stress Induced Desorption of Calcium Ions from Dipolar Lipid Membranes.
AB  - The interaction between multivalent ions and lipid membranes with saturated tails
      and dipolar (net neutral) headgroups can lead to adsorption of the ions onto the
      membrane. The ions charge the membranes and contribute to electrostatic repulsion
      between them, in a similar manner to membranes containing charged lipids. Using
      solution X-ray scattering and the osmotic stress method, we measured and modeled
      the pressure-distance curves between partially charged membranes containing
      mixtures of charged (1,2-dilauroyl-sn-glycero-3-phospho-l-serine, DLPS) and
      dipolar (1,2-dilauroyl-sn-glycero-3-phosphocholine, DLPC) lipids over a wide
      range of membrane charge densities. We then compared these pressure-distance
      curves with those of DLPC membranes in the presence of 10 mM CaCl2. Our data and
      modeling show that when low osmotic stress is applied to the DLPC bilayers, the
      membrane charge density is equivalent to that of a charged membrane containing
      ca. 4 mol % DLPS and 96 mol % DLPC. As the osmotic stress increased, the charge
      density of the DLPC membrane decreased and resembled that of a membrane
      containing ca. 1 mol % DLPS. These data are consistent with desorption of the
      calcium ions from the DLPC membrane with increasing osmotic stress.

PMID- 28514857
TI  - Pathways for Gold Nucleation and Growth over Protein Cages.
AB  - Proteins are widely utilized as templates in biomimetic synthesis of gold
      nanocrystals. However, the role of proteins in mediating the pathways for gold
      nucleation and growth is not well understood, in part because of the lack of
      spatial resolution in probing the complicated biomimetic mineralization process.
      Self-assembled protein cages, with larger size and symmetry, can facilitate in
      the visualization of both biological and inorganic components. We have utilized
      bacteriophage P22 protein cages of ~60 nm diameter for investigating the
      nucleation and growth of gold nanocrystals. By adding a gold precursor into the
      solution with preexisting protein cages and a reducing agent, gold
      nuclei/prenucleation clusters form in solution, which then locate and attach to
      specific binding sites on protein cages and further grow to form gold
      nanocrystals. By contrast, addition of the reducing agent into the solution with
      incubated gold precursor and protein cages leads to the formation of gold
      nuclei/prenucleation clusters both in solution and on the surface of protein
      cages that then grow into gold nanocrystals. Because of the presence of cysteine
      (Cys) with strong gold-binding affinity, gold nanocrystals tend to bind at
      specific sites of Cys, irrespective of the binding sites of gold ions. Analyzing
      the results obtained using these alternate routes provide important insights into
      the pathways of protein-mediated biomimetic nucleation of gold that challenge the
      importance of incubation, which is widely utilized in the biotemplated synthesis
      of inorganic nanocrystals.

PMID- 28514856
TI  - Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino
      Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces.
AB  - Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a
      high affinity for integrin receptors, that are assembled on CB[8]-methylviologen
      modified surfaces. The multivalency in the knottins stems from the number of
      tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary
      complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV2+).
      The binding affinity of the knottins with CB[8] and MV2+ surfaces was evaluated
      using surface plasmon resonance spectroscopy. Specific binding occurred, and the
      affinity increased with the valency of tryptophans on the knottin. Additionally,
      increased multilayer formation was observed, attributed to homoternary complex
      formation between tryptophan residues of different knottins and CB[8]. Thus, we
      were able to control the surface coverage of the knottins by valency and
      concentration. Cell experiments with mouse myoblast (C2C12) cells on the self
      assembled knottin surfaces showed specific integrin recognition by the RGD
      displaying knottins. Moreover, cells were observed to elongate more on the
      supramolecular knottin surfaces with a higher valency, and in addition, more
      pronounced focal adhesion formation was observed on the higher-valency knottin
      surfaces. We attribute this effect to the enhanced coverage and the enhanced
      affinity of the knottins in their interaction with the CB[8] surface.
      Collectively, these results are promising for the development of biomaterials
      including knottins via CB[8] ternary complexes for tunable interactions with
      cells.

PMID- 28514858
TI  - Cholesterol Based Surface Active Ionic Liquid That Can Form Microemulsions and
      Spontaneous Vesicles.
AB  - In this article, we have reported the synthesis and physicochemical
      characterization of a novel l-glycine amino acid derived cholesterol based
      surface active ionic liquid (SAIL). This SAIL has been explored for the
      preparation of ionic liquid (IL)-in-oil microemulsions and vesicles. The
      formation of IL-in-oil microemulsion is characterized by construction of a
      ternary phase diagram, dynamic light scattering (DLS) measurement, proton nuclear
      magnetic resonance (1H NMR) study, fluorescence measurement using coumarin 480 (C
      480) as a molecular probe, and also by recording the diffusion behavior of the
      molecular probe rhodamine 6G (R6G) in microemulsion droplets through the
      fluorescence correlation spectroscopy (FCS) technique. Similarly, the spontaneous
      vesicle formation from the SAIL in water has been established using DLS,
      transmission electron microscopy (TEM), cryogenic-transmission electron
      microscopy (cryo-TEM), field emission scanning electron microscopy (FESEM),
      atomic force microscopy (AFM), FCS, and fluorescence lifetime imaging microscopy
      (FLIM) measurements. These aggregates may potentially serve as good biomimicking
      models and possible drug carriers.

PMID- 28514859
TI  - What Does "Important New Physical Insights" Mean? Tips for Writing Better Papers.

PMID- 28514860
TI  - What Does "Important New Physical Insights" Mean? Tips for Writing Better Papers.

PMID- 28514861
TI  - Spotlights: Volume 8, Issue 10.

PMID- 28514862
TI  - Importance of Solvation for the Accurate Prediction of Oxygen Reduction
      Activities of Pt-Based Electrocatalysts.

PMID- 28514863
TI  - Surface dependent contact activation of factor XII and blood plasma coagulation
      induced by mixed thiol surfaces.
AB  - Studies of the activation of FXII in both platelet poor plasma and in neat buffer
      solutions were undertaken for a series of mixed thiol self-assembled monolayers
      spanning a broad range of water wettability. A wide spectrum of carboxyl/methyl-,
      hydroxyl/methyl-, and amine/methyl-thiol modified surfaces were prepared,
      characterized, and then utilized as the procoagulant materials in a series of
      FXII activation studies. X-ray photoelectron spectroscopy was utilized to verify
      the sample surface's thiol composition and contact angles measured to determine
      the sample surface's wettability. These samples were then used in in vitro
      coagulation assays using a 50% mixture of recalcified plasma in phosphate
      buffered saline. Alternatively, the samples were placed into purified FXII
      solutions for 30 min to assess FXII activation in neat buffer solution. Plasma
      coagulation studies supported a strong role for anionic surfaces in contact
      activation, in line with the traditional models of coagulation, while the
      activation results in neat buffer solution demonstrated that FXIIa production is
      related to surface wettability with minimum levels of enzyme activation observed
      at midrange wettabilities, and no statistically distinguishable differences in
      FXII activation seen between highly wettable and highly nonwettable surfaces.
      Results demonstrated that the composition of the solution and the surface
      properties of the material all contribute to the observation of contact
      activation, and the activation of FXII is not specific to anionic surfaces as has
      been long believed.

PMID- 28514865
TI  - Therapeutic alliance in youth with autism spectrum disorder receiving cognitive
      behavioral treatment for anxiety.
AB  - Symptoms of autism spectrum disorder may influence alliance in psychotherapy.
      This study examined therapeutic alliance and its relationship with child
      characteristics and anxiety treatment outcomes in youth with autism spectrum
      disorder. Youth ( N = 64) with autism spectrum disorder and co-occurring anxiety
      (7-16 years, IQ > 70) received 16 sessions of modular cognitive-behavioral
      therapy. Post-treatment therapist, youth and parent ratings of alliance as well
      as pre- and post-treatment ratings of child behavior were gathered. Ratings of
      alliance were commensurate to ratings seen in children without autism spectrum
      disorder. Measures of treatment outcome, but not pretreatment characteristics,
      were significantly associated with therapist ratings of alliance strength. Data
      suggest that therapeutic alliance may not be impaired in anxious youth with
      autism spectrum disorder and may be associated with treatment outcome.

PMID- 28514864
TI  - Application of advanced sampling and analysis methods to predict the structure of
      adsorbed protein on a material surface.
AB  - The use of standard molecular dynamics simulation methods to predict the
      interactions of a protein with a material surface have the inherent limitations
      of lacking the ability to determine the most likely conformations and
      orientations of the adsorbed protein on the surface and to determine the level of
      convergence attained by the simulation. In addition, standard mixing rules are
      typically applied to combine the nonbonded force field parameters of the solution
      and solid phases the system to represent interfacial behavior without validation.
      As a means to circumvent these problems, the authors demonstrate the application
      of an efficient advanced sampling method (TIGER2A) for the simulation of the
      adsorption of hen egg-white lysozyme on a crystalline (110) high-density
      polyethylene surface plane. Simulations are conducted to generate a Boltzmann
      weighted ensemble of sampled states using force field parameters that were
      validated to represent interfacial behavior for this system. The resulting
      ensembles of sampled states were then analyzed using an in-house-developed
      cluster analysis method to predict the most probable orientations and
      conformations of the protein on the surface based on the amount of sampling
      performed, from which free energy differences between the adsorbed states were
      able to be calculated. In addition, by conducting two independent sets of TIGER2A
      simulations combined with cluster analyses, the authors demonstrate a method to
      estimate the degree of convergence achieved for a given amount of sampling. The
      results from these simulations demonstrate that these methods enable the most
      probable orientations and conformations of an adsorbed protein to be predicted
      and that the use of our validated interfacial force field parameter set provides
      closer agreement to available experimental results compared to using standard
      CHARMM force field parameterization to represent molecular behavior at the
      interface.

PMID- 28514867
TI  - Acute, Temporary, Unilateral Facial Nerve Palsy After Dermatologic Surgery: A
      Report of 3 Cases.
AB  - Facial nerve dysfunction can be functionally and cosmetically debilitating and is
      commonly associated with high anxiety for patients. We report 3 cases of
      temporary, unilateral facial nerve palsy following dermatologic surgery under
      local anaesthesia over the preauricular cheek and mandibular angle, which, to our
      knowledge, has not been reported in the literature. Given its frightening
      presentation mimicking a stroke, it is essential for dermatologists to become
      aware of this complication to inform their patients more thoroughly. Thus, when
      performing facial surgery over these regions, we recommend that dermatologists
      include this rare complication and its good prognosis in the consenting process
      to minimise anxiety for those who experience it intra- or postoperatively.

PMID- 28514866
TI  - Social support and amphetamine-type stimulant use among female sex workers in
      China.
AB  - BACKGROUND: Existing research has suggested a positive role of social support in
      reducing drug use among female sex workers (FSWs). However, there is limited
      research on the role of social support in amphetamine-type stimulant (ATS) use
      among FSWs in China. This study explored the present situation of ATS use among
      FSWs in Guangxi, China and examined the associations of different types of social
      support from different sources with ATS use. METHOD: A sample of 1022 FSWs was
      recruited from 56 commercial sex venues in Guangxi Autonomous Region in China.
      Bivariate comparison was used to compare demographic characteristics and source
      of emotional or tangible social support across frequency of ATS use among FSWs.
      The relationship between social support and ATS use was examined using multiple
      ordinal logistic regression models controlling for the potential confounding
      effects of demographic variables. RESULTS: The multiple ordinal logistic
      regression indicated that FSWs who were from younger age groups (aOR = 10.88 for
      age group <20; aOR = 2.80 for age group 20-23), and from all higher-income venues
      (aOR = 1.96 for venue level 1; aOR = 2.28 for venue level 2; aOR = 1.81 for venue
      level 3) tended to use ATS more frequently. They also tended to use ATS more
      frequently when they depended on their boyfriends (aOR = 1.08) for emotional
      support or on their co-workers for tangible support (aOR = 1.17). CONCLUSIONS:
      Different types of social support from different sources can be either positively
      or negatively associated with ATS use among FSWs, therefore, the future
      intervention efforts should differentiate and target different types and
      different sources of social support in response to the living and work conditions
      of FSWs.

PMID- 28514869
TI  - Bullying-related behaviour in adolescents with autism: Links with autism severity
      and emotional and behavioural problems.
AB  - This study examined the association between peer-reported bullying-related
      behaviours (bully, victim, outsider and defender), age, gender, autism severity
      and teacher-rated emotional and behavioural problems in adolescents with autism
      spectrum disorder, using a multi-informant approach. The sample comprised 120
      adolescents (11% girls, Mage = 15.6 years, standard deviation = 1.89 years)
      attending a special school for children with autism. Results show that bullying
      decreased with age and was associated with behavioural problems, while
      victimisation was only associated with peer problems - a pattern of results
      comparable to studies exploring these associations in typically developing
      children. However, there were few associations among study variables for outsider
      or defender behaviours in this sample. Notably, children's autism severity did
      not significantly predict bullying-related behaviours.

PMID- 28514868
TI  - Phytochemical composition and in vitro screening of the antimicrobial activity of
      essential oils on oral pathogenic bacteria.
AB  - In this study, the activity of essential oils (EOs) against microorganisms
      involved in oral diseases was evaluated. Fourteen EOs were selected and subjected
      to gas chromatographic analysis, including Illicium verum, Eucaliptus globulus,
      Eugenia caryophyllata, Leptospermum scoparium, Mentha arvensis, Mentha piperita,
      Myrtus communis, Salvia officinalis, Melaleuca alternifolia, Rosmarinus
      officinalis, Lavandula x intermedia, Thymus capitatus and Thymus vulgaris. These
      EOs were tested for their antimicrobial activity on Streptococcus mutans and
      Lactobacillus species clinically isolated from dental surgery patients. The
      antibacterial activity was evaluated by means of the disc diffusion and the
      minimum inhibitory concentration (MIC). Five EOs, having shown an interesting
      antimicrobial activity, were selected for a second screening in combination
      between them and with chlorhexidine. From the second assays, two EO-EO and three
      EO-chlorhexidine associations gave interesting results as potential constituents
      of mouthwashes, especially for the contribution of oxygenated monoterpenes,
      including menthol, thymol and carvacrol.

PMID- 28514870
TI  - Biomarker Profile of Sepsis-Associated Coagulopathy Using Biochip Assay for
      Inflammatory Cytokines.
AB  - Disseminated intravascular coagulation (DIC) is a major pathophysiological
      mechanism of sepsis and greatly increases the risk of death in septic patients.
      Disseminated intravascular coagulation is a complex physiological phenomenon that
      involves inappropriate activation of coagulation, inflammation, and endothelial
      processes. The purpose of this study was to analyze the levels of inflammatory
      cytokines in the plasma of patients with DIC in order to compare the measured
      levels with those from healthy individuals, draw correlations, and provide a
      basis for further biomarker panel development. The inflammatory biomarkers
      interleukin (IL) 1beta, IL-6, IL-8, IL-10, interferon (IFN) gamma, vascular
      endothelial growth factor (VEGF), tumor necrosis factor (TNF) alpha, monocyte
      chemoattractant protein (MCP)-1, and epidermal growth factor (EGF) showed
      significant ( P < .05) elevation in patients with DIC. Interestingly, while
      numerous correlations were present between IL-beta, IL-6, IL-8, IL-10, IFN-gamma,
      TNF-alpha, MCP-1, and many of the inflammatory cytokines measured, VEGF and EGF
      exhibited much less extensive correlation, suggesting that their involvement in
      DIC may be independent of the other investigated inflammatory markers.

PMID- 28514871
TI  - Pulse Wave Velocity: Retrospective Analysis in a Balkan Normotensive and
      Hypertensive Population: A Study of 9923 Patients.
AB  - We compared pulse wave velocity (PWV) between hypertensive patients and control
      patients to identify demographics and patient characteristics related to PWV. We
      retrospectively analyzed 9923 participants (3105 controls and 6818 hypertensive
      patients) from 5 outpatient hypertensive clinics (in Serbia and Greece). Pulse
      wave velocity had different distribution between controls and hypertensive
      patients ( P < .001). The magnitude of PWV increase was related to blood pressure
      (BP) category (from optimal to stage III hypertension; P < .001). Even in
      hypertensive patients with systolic BP (SBP) <140 and/or diastolic BP (DBP) <90
      mm Hg, PWV was greater than in control patients ( P < .001). Pulse wave velocity
      was associated with almost all baseline characteristics of hypertensive patients
      (body mass index [BMI], gender, age, SBP, DBP, smoking status, and heart rate; P
      < .001). This association remained after adjustment of PWV confounders. There
      were 2231 (32.7%) hypertensive patients who had reached SBP <140 mm Hg and DBP
      <90 mm Hg. Pulse wave velocity was increased in hypertensive patients, and the
      degree of PWV increase was associated with baseline BP as well as with
      anthropometric parameters (eg, BMI, gender, age, heart rate, and smoking status).

PMID- 28514872
TI  - Best Medical Treatment for Patients with Carotid Stenosis: Evidence-Based
      Medicine or Wishful Thinking?

PMID- 28514873
TI  - Unpacking community mobility: a preliminary study into the embodied experiences
      of stroke survivors.
AB  - PURPOSE: To enrich the discussion on mobility in stroke rehabilitation by
      translating theoretical repertoires of mobility from the context of geography to
      rehabilitation. METHOD: Qualitative research methodology was applied, and
      included in-depth interviews with stroke survivors. RESULTS: This study revealed:
      (a) social and material differences in clinical, private and public places; (b)
      ambivalences and shifting tensions in bodily, family and community life; (c)
      differences in access to resources to be used for mobility. Moving around safely
      was not a matter of being physically able to walk independently, it also involved
      dealing with different human actors - such as children, partners and shoppers,
      and non-human actors - such as doorbells and traffic rules. Stroke survivors had
      to balance exercise and training, family and working life, and leisure and
      pleasure, and to renegotiate their mobility in each context. CONCLUSIONS: Our
      study showed that mobility has many aspects that interact with each other in
      multiple ways for stroke survivors when they return home and thereafter. The
      current focus on adherence to mobility and exercise training at home needs to be
      critically reviewed as it does not capture the multiplicities embodied in real
      life settings. Implications for rehabilitation Rehabilitation medicine needs to
      consider mobility as a way to connect places that are meaningful to individuals
      rather than as movements from A to B. Clinical outcome measurement tools, such as
      the 10-meter walk test, are inadequate for evaluating participation in the
      mobility domain at home or in the community. Mobility issues at the participation
      domain need to be considered in "how they hang together" rather than
      distinguished in different disciplinary domains. Rehabilitation practitioners
      should teach stroke survivors concrete strategies on how to creatively deal with
      the ambivalences and tensions around mobility in home and community life.

PMID- 28514874
TI  - Oncolytic Recombinant Vesicular Stomatitis Virus (VSV) Is Nonpathogenic and
      Nontransmissible in Pigs, a Natural Host of VSV.
AB  - Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally
      causes disease in livestock including horses, cattle and pigs. The two main
      identified VSV serotypes are New Jersey (VSNJV) and Indiana (VSIV). VSV is a
      rapidly replicating, potently immunogenic virus that has been engineered to
      develop novel oncolytic therapies for cancer treatment. Swine are a natural host
      for VSV and provide a relevant and well-established model, amenable to biological
      sampling to monitor virus shedding and neutralizing antibodies. Previous reports
      have documented the pathogenicity and transmissibility of wild-type isolates and
      recombinant strains of VSIV and VSNJV using the swine model. Oncolytic VSV
      engineered to express interferon-beta (IFNbeta) and the sodium iodide symporter
      (NIS), VSV-IFNbeta-NIS, has been shown to be a potent new therapeutic agent
      inducing rapid and durable tumor remission following systemic therapy in
      preclinical mouse models. VSV-IFNbeta-NIS is currently undergoing clinical
      evaluation for the treatment of advanced cancer in human and canine patients. To
      support clinical studies and comprehensively assess the risk of transmission to
      susceptible species, we tested the pathogenicity and transmissibility of
      oncolytic VSV-IFNbeta-NIS using the swine model. Following previously established
      protocols to evaluate VSV pathogenicity, intradermal inoculation with 107 TCID50
      VSV-IFNbeta-NIS caused no observable symptoms in pigs. There was no detectable
      shedding of infectious virus in VSV-IFNbeta-NIS in biological excreta of
      inoculated pigs or exposed naive pigs kept in direct contact throughout the
      experiment. VSV-IFNbeta-NIS inoculated pigs became seropositive for VSV
      antibodies, while contact pigs displayed no symptoms of VSV infection, and
      importantly did not seroconvert. These data indicate that oncolytic VSV is both
      nonpathogenic and not transmissible in pigs, a natural host. These findings
      support further clinical development of oncolytic VSV-IFNbeta-NIS as a safe
      therapeutic for human and canine cancer.

PMID- 28514875
TI  - Identification of novel Nicotinamide Phosphoribosyltransferase (NAMPT) inhibitors
      using computational approaches.
AB  - Nicotinamide Phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the
      biosynthesis of NAD. Cancer cells have elevated poly [ADP-Ribose] polymerase 1
      (PARP) activity as well as the immense necessity of ATP: thereby consuming NAD at
      a higher rate than normal tissues. The perturbation of these intracellular
      processes is more sensitive and highly dependent on NAMPT to maintain the
      required NAD levels. Functional inhibition of NAMPT is, therefore, a promising
      drug target in therapeutic oncology. In this study, the importance of
      intermolecular contacts was realized based on contact occupancy and favorable
      energetic from molecular dynamic simulation to discern non-critical contacts of
      four different classes of potential NAMPT inhibitor bound complexes. Further,
      pharmacophore modeling, molecular docking, a quantum mechanical properties and MD
      simulation, as well as active site residual network communication were employed
      to identify potential leads. Present studies identified two leads, 2 and 3 which
      have better binding free energy compared to known inhibitors and showed stable
      hydrogen bonding and hydrophobic contacts with beta barrel cavity lining residues
      in the active site of the dimer interface (A'B). Lead 2 containing fluorene as
      central core and lead 3 having phenyl-benzamide as a core showed stable moiety
      which was observed from electronic property analysis. Active site residual
      communication in identified leads bound complex also showed similarity to known
      inhibitor complexes. Compounds containing these moieties were not reported until
      now against NAMPT inhibition and can be considered as novel cores for future
      development of drugs to inhibit NAMPT function.

PMID- 28514876
TI  - Potential support ratios: Cohort versus period perspectives.
AB  - The 'prospective potential support ratio' has been proposed by researchers as a
      measure that accurately quantifies the burden of ageing, by identifying the
      fraction of a population that has passed a certain measure of longevity, for
      example, 17 years of life expectancy. Nevertheless, the prospective potential
      support ratio usually focuses on the current mortality schedule, or period life
      expectancy. Instead, in this paper we look at the actual mortality experienced by
      cohorts in a population, using cohort life tables. We analyse differences between
      the two perspectives using mortality models, historical data, and forecasted
      data. Cohort life expectancy takes future mortality improvements into account,
      unlike period life expectancy, leading to a higher prospective potential support
      ratio. Our results indicate that using cohort instead of period life expectancy
      returns around 0.5 extra younger people per older person among the analysed
      countries. We discuss the policy implications implied by our cohort measures.

PMID- 28514877
TI  - The assumptions of cognitive neuropsychology: Reflections on Caramazza (1984,
      1986).
AB  - Approximately 30 years ago, Caramazza (1984. The logic of neuropsychological
      research and the problem of patient classification in aphasia. Brain and
      Language, 21, 9-20; 1986. On drawing inferences about the structure of normal
      cognitive systems from the analysis of patterns of impaired performance. Brain
      and Language, 5, 41-66) proposed that cognitive neuropsychology needs to make
      four assumptions in order for its inferences from pathological performance to the
      structure of intact cognitive systems to be justifiable. These assumptions were:
      fractionation, modularity, transparency and universality. Analysis of the current
      status of these assumptions leads me to conclude that all four remain defensible
      today.

PMID- 28514878
TI  - Anticoagulant cessation following atrial fibrillation ablation: limits of the ECG
      guided approach.
AB  - INTRODUCTION: Long-term cessation of oral anticoagulation (OAC) following
      successful catheter or surgical ablation of atrial fibrillation (AF) is debated.
      Usually, in the presence of sinus rhythm at serial ECG recordings, the CHADS2,
      CHA2DS2VASc, and HAS-BLED scores are adopted to guide decision regarding OAC
      management. Areas covered: The safety of OAC cessation in patients without
      recurrent AF but with historically elevated risk for thromboembolism remains
      largely unknown. Taking the cue from two clinical cases, we provide an updated
      summary of the latest evidence regarding how to manage OAC after a successful
      atrial fibrillation ablation. Expert commentary: The present clinical perspective
      suggests that, at least within patients with severely enlarged left atrium,
      previous cardiac surgery and catheter or surgical AF ablation, especially if
      repeated, assessment of atrial contractility by transthoracic echocardiography
      should be performed before discontinuing OAC in patients who maintain sinus
      rhythm, confirmed by serial ECG or Holter monitorings.

PMID- 28514879
TI  - Growth restriction: identifying fetuses at risk.
AB  - PURPOSE: Examine risks of intrauterine growth restriction (IUGR) and composite
      perinatal outcomes with estimated fetal weights (EFW) 10-20th%, and compare
      outcomes using umbilical artery Doppler (UAD). MATERIALS AND METHODS:
      Retrospective, cohort evaluating ultrasound (US) EFW 10-20th%, between 2002 and
      2012. Cases were identified with EFW % 10-20. Controls, EFW >20th% were obtained
      for each case, matched by gestational age, and US date. Unadjusted and adjusted
      logistic regression was used for outcomes. RESULTS: Seven hundred and sixty-seven
      cases met criteria with matched controls. Fetuses having EFW 10-20th% (GA 33.6 +/
      3.7 weeks) had increased IUGR on follow up ultrasound (OR 26.5[10.2-68.7], p <
      .01), small for gestational age (SGA) (OR 9.2 [6.9-12.3], p < .01), neonatal
      intensive care unit (NICU) admissions (OR 2.4 [1.6-3.6], p < .01), and composite
      perinatal morbidity (OR 7.8 [6.0-10.1], p < .01) on adjusted analyses. Abnormal
      UAD in cases had greater rates of 5 min Apgar <7, NICU admission and composite
      morbidity (p < .05). CONCLUSIONS: Pregnancies with EFW 10-20th% at the time of
      initial US are at increased risk for developing IUGR and being SGA at birth, with
      more NICU admissions and composite perinatal outcomes; abnormal UAD evaluation in
      cases conveyed further increase in outcomes.

PMID- 28514880
TI  - The uterocervical angle and its relationship with preterm birth.
AB  - OBJECTIVES: The objective of this study is to determine whether the uterocervical
      angle (UCA) correlates with the risk of spontaneous preterm birth (sPTB) < 34
      weeks and assess its interobserver variability. STUDY DESIGN: Case-control study
      of 275 women including 34 who started labor spontaneously and gave birth before
      34 weeks of gestation (preterm group) and 241 who gave birth at term (control
      group). Images used to report cervical length were re-measured for UCA. RESULTS:
      Mean UCA in the second trimester was wider in the preterm group (105.16 degrees )
      compared with the control group (94.53 degrees ), p = .015. The intraclass
      correlation coefficient was 0.821 (95% CI: 0.74-0.97) for masked interobserver
      variability, which implies correct agreement among UCA measurements. Mean UCA
      increased from the first to the second trimester (84.2 degrees  versus 94.5
      degrees ; p = .019). CONCLUSIONS: Wider UCA in the second trimester is related to
      sPTB. UCA measurement is a reproducible technique. UCA appears to increase from
      the first to the second trimester. Prospective studies, with ultrasound
      examinations aimed at measuring UCA in vivo, are needed to accurately assess the
      characteristics of this marker and its potential as a predictor of sPTB in
      clinical practice.

PMID- 28514882
TI  - Interventions in pain management for persons with an intellectual disability.
AB  - Pain is a multidimensional and subjective experience, and an ideal pain
      management regime needs to be comprehensive, integrative and involve all relevant
      persons. Multimodal interventions may include pharmacological, physical, social,
      psychological and spiritual approaches in order to address pain management at a
      molecular, functional, behavioural, cognitive and affective levels. Pain
      management interventions will vary according to pain aetiology, patient
      characteristics and preferences. In keeping with best practice guidelines for
      effective pain management, a structured approach incorporating an effective
      assessment of pain by the healthcare professional, identification of the source
      and type of pain and accurate documentation is essential. This article focuses on
      pharmacological and non-pharmacological pain management for individuals with
      intellectual disability.

PMID- 28514881
TI  - Trisomy 13 and the risk of gestational hypertensive disorders: a population-based
      study.
AB  - PURPOSE: To describe the rate and severity of gestational hypertensive disorders
      (GHDs) in pregnancies complicated by trisomy 13 (T13). MATERIALS AND METHODS:
      Retrospective cohort study of singleton deliveries in California from 2005 to
      2008 using vital statistics and ICD-9 data. We were interested in gestational
      hypertension (gHTN), preeclampsia with and without severe features (sPREX and
      PREX), and gestational age at delivery. Pregnancies and maternal complications
      affected by prenatally diagnosed T13 were compared to unaffected pregnancies.
      Regression models were used to compute adjusted odds ratios for pregnancy
      outcomes by T13 status. RESULTS: Of the 2,029,004 deliveries, 142 women had
      prenatally diagnosed T13. A diagnosis of GHD occurred in 26.8% of the T13
      pregnancies versus 6% of the non-T13 pregnancies (p < .001). This remained true
      for gHTN (9.2% versus 3.2%, p=.001), PREX (12% versus 2.2%, p < .001), and sPREX
      (8.5% versus 0.9%, p < .001). After adjusting for confounders, T13 pregnancies
      were 6.3-times more likely to be affected by GHD, and 12.5-times more likely to
      have sPREX. Delivery <37 and <32 weeks in the setting of GHD was 14.1-times and
      11.2-times likely among women with T13. CONCLUSIONS: Women with T13 pregnancies
      were significantly more likely to have gHTN, preeclampsia, sPREX, and to deliver
      <32 weeks.

PMID- 28514883
TI  - Bioethical analysis to the therapeutic use of Cannabis: Integrative review.
AB  - INTRODUCTION: Despite being considered as a contravention under some countries'
      legislation, the therapeutic use of Cannabis sativa has been growing in Brazil,
      due to the promising results observed in many pathologies. Such a scenario has
      fostered the need to deepen discussions on the subject and possibly revise
      legislation governing the substance use and access. OBJECTIVES: Identify the
      types of stigma related to the therapeutic use of Cannabis and describe the
      strategies people use to overcome stigma. METHODS: This integrative review was
      carried out in the databases PubMed, Scopus, CINAHL, MEDLINE, PsycINFO, Web of
      Science, and Cochrane Library, with 565 articles being retrieved. Triads' cross
      check were done, first maintaining the "cannabis" and "therapeutic use" pair,
      added by "stigma," "bioethics," "ethics," "social consequences," and "legal
      consequences." The final selection resulted in six articles. Ethical
      Consideration: However, the ethical issues that pervade and regulate decisions on
      this subject must be considered. RESULTS: Different dimensions and types of
      stigma related to the therapeutic use of Cannabis have been identified. The
      bioethical principle of autonomy was an expression of citizenship and human
      rights, mitigating internal conflicts related to self-stigma and the effects of
      external stigma on the person's life. CONCLUSION: It was possible to identify the
      types of stigma related to the therapeutic use of Cannabis is an internal
      dimension represented (self-stigma) and an external dimension, represented
      (social and structural stigmas) and to identify strategies adopted to face this
      stigma: skills training group for users, elaboration of laws and specific
      programs to clarify the therapeutic use of Cannabis with a greater social scope,
      and support for family members. Thus, contributing to the building of people's
      autonomy in a broader context of decision-making autonomy and executive autonomy
      will provide the development of people's capacity to perform complex tasks of
      self-management and, consequently, to continue promoting and preserving their
      decision-making process and their capacity to plan and perform tasks associated
      with managing their lives and their treatments.

PMID- 28514884
TI  - The association of placenta previa and assisted reproductive techniques: a meta
      analysis.
AB  - BACKGROUND: Several epidemiological studies have determined that assisted
      reproductive techniques (ART) can increase the risk of placenta previa. To date,
      only a meta-analysis has been performed for assessing the relationship between
      placenta previa and ART. This meta-analysis was conducted to estimate the
      association between placenta previa and ART in singleton and twin pregnancies.
      METHODS: A literature search was performed in major databases PubMed, Web of
      Science, and Scopus from the earliest possible year to April 2017. The
      heterogeneity across studies was explored by Q-test and I2 statistic. The
      publication bias was assessed using Begg's and Egger's tests. The results were
      reported using odds ratio (OR) and relative risk (RR) estimates with its 95%
      confidence intervals (CI) using a random-effects model. RESULTS: The literature
      search yielded 1529 publications until September 2016 with 1,388,592
      participants. The overall estimate of OR was 2.67 (95%CI: 2.01, 3.34) and RR was
      3.62 (95%CI: 0.21, 7.03) based on singleton pregnancies. The overall estimate of
      OR was 1.50 (95%CI: 1.26, 1.74) based on twin pregnancies. CONCLUSIONS: We showed
      based on odds ratio reports in observational studies that ART procedures are a
      risk factor for placenta previa.

PMID- 28514886
TI  - Physiological effects of prebiotics and its role in prevention of necrotizing
      enterocolitis in preterm neonates.
AB  - Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal
      emergencies in very low birth weight (VLBW) preterm neonates, affecting 7-14% of
      these neonates. Due to the seriousness of the disease, prevention of NEC is the
      most important goal. Current evidence from systematic review and meta-analysis
      revealed that probiotics are the most promising intervention in reduction of the
      incidence of NEC in VLBW neonates. As per the evidence, prebiotics modulate the
      composition of human intestine microflora to the benefit of the host by
      suppression of colonization of harmful microorganism and/or the stimulation of
      bifidobacterial growth, decreased stool viscosity, reduced gastrointestinal
      transit time, and better feed tolerance. Prebiotics may be potential alternatives
      or adjunctive therapies to probiotics, despite a lack of evidence supporting its
      clinical efficacy in prevention of NEC. In this article, we discuss evidence
      based physiological effects of prebiotics and its therapeutic role in prevention
      of NEC.

PMID- 28514885
TI  - Poorer maternal diet quality and increased birth weight.
AB  - OBJECTIVE: Maternal diet and gestational weight gain (GWG) influence birth weight
      and infant adiposity, which are important predictors of lifetime health. To
      better understand these relationships, we studied associations between maternal
      diet and GWG, adiposity, and birth weight in a well characterized cohort of
      pregnant women. STUDY DESIGN: Data were obtained from 41 term (>37 weeks),
      uncomplicated, singleton pregnancies according to pre-pregnancy BMI categories of
      normal (n = 11), overweight (n = 15), or obese (n = 15). Daily consumption of
      protein, fat, and carbohydrates and a Healthy Eating Index (HEI-2010) score were
      determined from 24 h food recall collections. Associations were modeled using
      multinomial logistic and linear regression. RESULTS: Neither the third trimester
      maternal diet quality nor the macronutrient consumption was associated with GWG
      after adjusting for pre-pregnancy BMI, maternal age, and parity. A ten-point
      lower HEI-2010 score was associated with 200 g higher infant birth weight and a
      1.0 cm longer length. However, maternal HEI-2010 and macronutrient composition
      were unrelated to infant percent body fat, ponderal index, or abdominal
      circumference. CONCLUSIONS: Poorer third trimester maternal diet quality was
      associated with higher birth weight and longer length, but was unrelated to
      markers of infant adiposity. GWG was independent of third trimester maternal diet
      composition and quality.

PMID- 28514887
TI  - Transanal Inspection and Management of Low Colorectal Anastomosis Performed With
      a New Technique: the TICRANT Study.
AB  - BACKGROUND: Anastomotic leakage is one of the most serious complications after
      rectal cancer surgery. METHOD: A prospective multicenter interventional study to
      assess a newly described technique of creating the colorectal and coloanal
      anastomosis. The primary outcome was to access the safety and efficacy of this
      technique in the reduction of anastomotic leak. RESULT: Fifty-three patients with
      rectal cancer who underwent low or ultra-low anterior resection were included in
      the study. There were 35 males and 18 females, with a median age of 68 years
      (range = 49-89 years). The median tumor distance from the anal verge was 8 cm
      (range = 4-12 cm), and the median body mass index was 24 kg/m2 (range = 20-35
      kg/m2). Thirty patients underwent open, 16 laparoscopic, and 7 robotic surgeries.
      Multiple firing (2-charges) was required in 30 patients to obtain a complete
      rectal division. Forty-five patients had colorectal anastomosis, and 8 patients
      had coloanal anastomosis. The protective ileostomy was created in 40 patients at
      the time of initial surgery. There was no mortality in the first 30 days
      postoperatively, and only 10 (19%) patients developed complications. There were 3
      anastomotic leakages (6%); 2 of them were subclinical with ileostomy created at
      initial operation and both were treated conservatively with transanal drainage
      and intravenous antibiotics. One patient required reoperation and ileostomy. The
      median length of hospital stay was 10 days (range = 4-20 days). CONCLUSION: Our
      technique is a safe and efficient method of creation of colorectal anastomosis.
      It is also a universal method that can be used in open, laparoscopic, and robotic
      surgeries.

PMID- 28514888
TI  - Seeing is believing - healthcare professionals' perceptions of a complex
      intervention to improve care towards the end of life: A qualitative interview
      study.
AB  - BACKGROUND: Methods to improve care, trust and communication are important in
      acute hospitals. Complex interventions aimed at improving care of patients
      approaching the end of life are increasingly common. While evaluating outcomes of
      complex interventions is essential, exploring healthcare professionals'
      perceptions is also required to understand how they are interpreted; this can
      inform training, education and implementation strategies to ensure fidelity and
      consistency in use. AIM: To explore healthcare professionals' perceptions of
      using a complex intervention (AMBER care bundle) to improve care for people
      approaching the end of life and their understandings of its purpose within
      clinical practice. DESIGN: Qualitative study of healthcare professionals.
      Analysis informed by Medical Research Council guidance for process evaluations.
      SETTING/PARTICIPANTS: A total of 20 healthcare professionals (12 nursing and 8
      medical) interviewed from three London tertiary National Health Service
      hospitals. Healthcare professionals recruited from palliative care, oncology,
      stroke, health and ageing, medicine, neurology and renal/endocrine services.
      RESULTS: Three views emerged regarding the purpose of a complex intervention
      towards the end of life: labelling/categorising patients, tool to change care
      delivery and serving symbolic purpose indirectly affecting behaviours of
      individuals and teams. All impact upon potential utility of the intervention.
      Participants described the importance of training and education alongside
      implementation of the intervention. However, adequate exposure to the
      intervention was essential to witness its potential added value or embed it into
      practice. CONCLUSION: Understanding differing interpretations of complex
      interventions is essential. Consideration of ward composition, casemix and
      potential exposure to the intervention is critical for their successful
      implementation.

PMID- 28514889
TI  - Pain perception in NICU: a pilot questionnaire.
AB  - PURPOSE: Neonatal pain management has made a great step forward over the last
      several years. Despite the drafting of International guidelines, an under
      treatment of neonatal pain is still reported. MATERIALS AND METHODS: Medical and
      paramedical personnel working in five Italian NICUs were asked to complete a
      questionnaire about pain management. The questionnaire was comprised of three
      sections: (i) brief explanation of the purpose; (ii) demographic information,
      including age, profession, religious beliefs, and hospital level; (iii)
      questionnaire about pain management and prevention. RESULTS: One-hundred and
      forty caregivers participated in this study. Non-pharmacological analgesia during
      heel prick or venipuncture was used by 64% and 60% of them, respectively; topical
      analgesia was performed in 13% of venipunctures; no analgesia was used in 30% of
      cases for both heel prick and venipuncture. In the case of lumbar puncture, 35%
      of participants used topical analgesia, 15% non-pharmacological approach, 10%
      opioids, and 6% intravenous paracetamol. While 65% of participants gave a score
      of 4 out of 5 about the importance of pain treatment, 39% of them reported that
      in their department no pain scales were used. CONCLUSIONS: Pain treatment in
      these NICUs is still far to be optimal. This nonetheless reflects a worldwide
      trend, which requires more attention on pain prevention, assessment, and
      treatment.

PMID- 28514891
TI  - Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative
      Stress in Rat Erythrocytes.
AB  - Erythrocytes are particularly vulnerable toward age-dependent oxidative stress
      mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy
      for the maintenance of redox balance as well as effective treatment of age
      associated diseases. Herein, we have investigated the beneficial effect of
      cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and
      inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic
      biguanide and activator of adenosine monophosphate kinase), against aging-induced
      oxidative stress in erythrocytes and plasma of aging rats. Male Wistar rats of
      age 4 (young) and 24 months (old) were coexposed to rapamycin (0.5 mg/kg body
      weight [b.w.]) and metformin (300 mg/kg b.w.), and data were compared with the
      response of rats receiving an independent exposure to these chemicals at similar
      doses. The exposure of individual candidate drugs significantly reversed the age
      dependent alterations in the endpoints associated with oxidative stress such as
      reactive oxygen species, ferric reducing ability of plasma, malondialdehyde,
      reduced glutathione, plasma membrane redox system, plasma protein carbonyl, and
      acetyl cholinesterase in erythrocytes and plasma of aging rats. However, the
      cotreatment with rapamycin and metformin showed a significant augmented effect
      compared with individual drug interventions on reversal of these age-dependent
      biomarkers of oxidative stress, suggesting a synergistic response. Thus, the
      findings open up further possibilities for the design of new combinatorial
      therapies to prevent oxidative stress- and age-associated health problems.

PMID- 28514890
TI  - Spatial recognition test: A novel cognition task for assessing topographical
      memory in mice.
AB  - Dysfunction in topographical memory is a core feature of several neurological
      disorders. There is a large unmet medical need to address learning and memory
      deficits as a whole in central nervous system disease. There are considerable
      efforts to identify pro-cognitive compounds but current methods are either
      lengthy or labour intensive. Our test used a two chamber apparatus and is based
      on the preference of rodents to explore novel environments. It was used firstly
      to assess topographical memory in mice at different retention intervals (RI) and
      secondly to investigate the effect of three drugs reported to be beneficial for
      cognitive decline associated with Alzheimer's disease, namely: donepezil,
      memantine and levetiracetam. Animals show good memory performance at all RIs
      tested under four hours. At the four-hour RI, animals show a significantly poorer
      memory performance which can be rescued using donepezil, memantine and
      levetiracetam. Using this test we established and validated a spatial recognition
      paradigm to address topographical memory in mice by showing a decremental time
      induced forgetting response and reversing this decrease in performance using
      pharmacological tools. The spatial recognition test differs from more commonly
      used visuospatial laboratory tests in both throughput capability and potentially
      neuroanatomical substrate. This test has the potential to be used to assess
      cognitive performance in transgenic animals, disease models and to screen
      putative cognitive enhancers or depressors.

PMID- 28514892
TI  - Single-case cognitive neuropsychology in the age of big data.
AB  - Historically, single-case studies of brain-damaged individuals have contributed
      substantially to our understanding of cognitive processes. However, the role of
      single-case cognitive neuropsychology has diminished with the proliferation of
      techniques that measure neural activity in humans. Instead, large-scale
      informatics approaches in which data are gathered from hundreds of neuroimaging
      studies have become popular. It has been claimed that utilizing these informatics
      approaches can address problems found in single imaging studies. We first discuss
      reasons for why cognitive neuropsychology is thought to be in decline. Next, we
      note how these informatics approaches, while having benefits, are not
      particularly suited for understanding functional architectures. We propose that
      the single-case cognitive neuropsychological approach, which is focused on
      developing models of cognitive processing, addresses several of the weaknesses
      inherent in informatics approaches. Furthermore, we discuss how using neural data
      from brain-damaged individuals provides data that can inform both cognitive and
      neural models of cognitive processing.

PMID- 28514893
TI  - Cytocompatible polyion complex gel of poly(Pro-Hyp-Gly) for simultaneous rat bone
      marrow stromal cell encapsulation.
AB  - Polyion complex (PIC) gel of poly(Pro-Hyp-Gly) was successfully fabricated by
      simply mixing polyanion and polycation derivatives of poly(Pro-Hyp-Gly), a
      collagen-like polypeptide. The polyanion, succinylated poly(Pro-Hyp-Gly), and the
      polycation, arginylated poly(Pro-Hyp-Gly), contain carboxy (pKa = 5.2) and
      guanidinium (pKa = 12.4) groups, respectively. Mixing the polyanion and the
      polycation at physiological pH (pH = 7.4) resulted in PIC gel. The hydrogel
      formation was optimum at an equimolar ratio of carboxy to guanidinium groups,
      suggesting that ionic interaction is the main determinant for the hydrogel
      formation. The hydrogel was successfully used for simultaneous rat bone marrow
      stromal cell encapsulation. The encapsulated cells survived and proliferated
      within the hydrogel. In addition, the cells exhibited different morphology in the
      hydrogel compared with cells cultured on a tissue culture dish as a two
      dimensional (2D) control. At day one, a round morphology and homogeneous single
      cell distribution were observed in the hydrogel. In contrast, the cells spread
      and formed a fibroblast-like morphology on the 2D control. After three days, the
      cells in the hydrogel maintained their morphology and some of them formed
      multicellular aggregates, which is similar to cell morphology in an in vivo
      microenvironment. These results suggest that the PIC gel of poly(Pro-Hyp-Gly) can
      serve as a cytocompatible three-dimensional scaffold for stem cell encapsulation,
      supporting their viability, proliferation, and in vivo-like behavior.

PMID- 28514894
TI  - Successful Repair of Acute Type B and Retrograde Type A Aortic Dissection With
      Kidney Ischemia.
AB  - Acute dissection of thoracic aorta carries a risk of renal ischemia followed by
      the development of a kidney failure. The optimal surgical and nonsurgical
      management of these patients, timing of intervention, and the factors predicting
      renal recovery are not well delineated and remain controversial. We present a
      case of acute type B thoracic aortic dissection with left kidney ischemia.
      Evaluation of renal function was performed by the means of internationally
      accepted Risk, Injury, Failure, Loss of kidney function, End stage kidney disease
      and Acute Kidney Injury Network classifications for acute kidney injury, renal
      duplex sonography, and intravascular ultrasound that demonstrated left renal
      artery dissection with a flap completely compressing the true lumen. The patient
      underwent thoracic endovascular aortic repair and left renal artery stent and
      recovered well. Six months later, at the follow-up visit, retrograde type A
      aortic dissection was found, which was successfully repaired. Reversal of renal
      ischemia after aortic dissection depends on the precise assessment of renal
      function and prompt intervention.

PMID- 28514895
TI  - Outcomes After Use of Aortouniiliac Endoprosthesis Versus Modular or Unibody
      Bifurcated Endoprostheses for Endovascular Repair of Ruptured Abdominal Aortic
      Aneurysms.
AB  - OBJECTIVES: Outcomes after endovascular repair (EVAR) of ruptured abdominal
      aortic aneurysms (rAAAs) have been widely published. There is, however,
      controversy on the role of the use of aortouniiliac endoprosthesis (AUI) versus
      modular or unibody bifurcated endoprosthesis (MUB) for repair of rAAAs. We study
      and compare 30-day outcomes after use of AUI and MUB for all rAAAs focusing
      specifically on patients with instability. MATERIALS AND METHODS: Patients who
      underwent EVAR for rAAA (n = 425) using AUI (n = 55; 12.9%) and MUB (n = 370;
      87.1%) were identified from the American College of Surgeons' National Surgical
      Quality Improvement Program (2005-2010) database. Univariable and multivariable
      logistic regression analyses were performed. RESULTS: No significant difference (
      P > .5) was seen in comorbidities between patients who underwent EVAR with AUI or
      MUB; there was also no change in endoprosthesis use from 2005 to 2010 ( P = .7).
      Patients who underwent EVAR with AUI more commonly had a history of peripheral
      arterial procedure (10.9% vs 4.6%; P = .053) and preoperative transfusion of >4 U
      packed red blood cells (18.2% vs 6.8%; P = .004). Use of AUI versus MUB was
      associated with more 30-day wound complications (16.4% vs 6.2%; P = .01), return
      to operating room (38.2% vs 20.0%; P = .003), and mortality (34.5% vs 21.4%; P =
      .03). On multivariable analysis, use of AUI was associated with an increased risk
      of 30-day mortality (odds ratio: 2.4; 95% confidence interval: 1.1-5.3). On
      subanalysis of the cohort for only the patients with unstable rAAA (n = 159; AUI
      = 29 and MUB = 130), 30-day mortality for AUI versus MUB was still higher but not
      statistically significant (44.8% vs 32.3%; P = .2). CONCLUSION: Endovascular
      repair for ruptured AAA using aortouniliac endoprosthesis is associated with
      higher 30-day mortality than using modular or unibody bifurcated endoprosthesis.

PMID- 28514896
TI  - "Snare-Ride": A Bailout Technique to Catheterize Target Vessels With Unfriendly
      Anatomy in Branched Endovascular Aortic Repair.
AB  - PURPOSE: To describe a novel endovascular bailout technique for successful
      completion of target vessel stenting during branched stent-graft repair of
      thoracoabdominal aortic aneurysms (TAAA) after encountering difficulties with
      standard catheterization techniques. TECHNIQUE: Technical difficulties when using
      fenestrated and branched grafts should be expected, especially in difficult
      anatomy or when an off-the-shelf device (eg, standard 4-branch device) is used
      that does not perfectly "match" the anatomy. The "snare-ride technique"
      facilitates antegrade transaxillary side branch catheterization and stent
      placement during TAAA branched grafting using a snare via a transfemoral
      approach. The branch of the graft is catheterized from an axillary access. The
      respective target vessel is then catheterized via a femoral access. An Indy snare
      is advanced over the transfemoral wire and positioned near the entrance of the
      target vessel. The transaxillary wire inside the branch of the graft is then
      advanced, snared, and pushed inside the target vessel with the snare. The
      procedure is thereafter continued with antegrade bridging of the target vessel in
      routine fashion. CONCLUSION: The snare-ride technique can be a useful maneuver to
      catheterize target vessels with difficult anatomy in TAAA branched stent-graft
      repair. Early experience shows safety and feasibility.

PMID- 28514897
TI  - Biomaterials and Bioactive Agents in Spinal Fusion.
AB  - Management of degenerative spine pathologies frequently leads to the need for
      spinal fusion (SF), where bone growth is induced toward stabilization of the
      interventioned spine. Autologous bone graft (ABG) remains the gold-standard
      inducer, whereas new bone graft substitutes attempt to achieve effective de novo
      bone formation and solid fusion. Limited fusion outcomes have driven motivation
      for more sophisticated and multidisciplinary solutions, involving new
      biomaterials and/or biologics, through innovative delivery platforms. The present
      review will analyze the most recent body of literature that is focused on new
      approaches for consistent bone fusion of spinal vertebrae, including the
      development of new biomaterials that pursue physical and chemical aptitudes; the
      delivery of growth factors (GF) to accelerate new bone formation; and the use of
      cells to improve functional bone development. Bone graft substitutes currently in
      clinical practice, such as demineralized bone matrix and ceramics, are still used
      as a starting point for the study of new bioactive agents. Polyesters such as
      polycaprolactone and polylactic acid arise as platforms for the development of
      composites, where a mineral element and cell/GF constitute the delivery system.
      Exciting fusion outcomes were obtained in several small and large animal models
      with these. On what regards bioactive agents, mesenchymal stem cells,
      preferentially derived from the bone marrow or adipose tissue, were studied in
      this context. Autologous and allogeneic approaches, as well as osteogenically
      differentiated cells, have been tested. These cell sources have further been
      genetically engineered for specific GF expression. Nevertheless, results on
      fusion efficacy with cells have been inconsistent. On the other hand, the
      delivery of GF (most commonly bone morphogenetic protein-2 [BMP-2]) has provided
      favorable outcomes. Complications related to burst release and dosing are still
      the target of research through the development of controlled release systems or
      alternative GF such as Nel-like molecule-1 (NELL-1), Oxysterols, or COMP-Ang1.
      Promising solutions with new biomaterial and GF compositions are becoming closer
      to the human patient, as these evidence high-fusion performance, while offering
      cost and safety advantages. The use of cells has not yet proved solid benefits,
      whereas a further understanding of cell behavior remains a challenge.

PMID- 28514899
TI  - Clinical Positioning Accuracy for Multisession Stereotactic Radiotherapy With the
      Gamma Knife Perfexion.
AB  - Multisession stereotactic radiation therapy is increasingly being seen as a
      preferred option for intracranial diseases in close proximity to critical
      structures and for larger target volumes. The objective of this study is to
      investigate the reproducibility of the Extend system from Elekta. A retrospective
      review was conducted for all patients treated with multisession Gamma Knife
      between July 2010 and June 2015, including both malignant and benign lesions.
      Eighty-four patients were treated in this 5-year span. The average residual daily
      setup uncertainty was 0.48 (0.19) mm. We compare measurements of setup
      uncertainty from the Extend system to measurements performed with a linac-based
      approach previously used in our center. The Extend system has significantly
      reduced setup uncertainty for fractionated intracranial treatments at our
      institution. Positive results were observed in a small population of edentulous
      patients. The Extend system compares favorably with other approaches to
      delivering intracranial stereotactic radiotherapy and is a robust, simple-to-use,
      and precise method for treating multisession intracranial lesions.

PMID- 28514898
TI  - Assessment of Cryosurgical Device Performance Using a 3D Tissue-Engineered Cancer
      Model.
AB  - As the clinical use of cryoablation for the treatment of cancer has increased, so
      too has the need for knowledge on the dynamic environment within the frozen mass
      created by a cryoprobe. While a number of factors exist, an understanding of the
      iceball size, critical isotherm distribution/penetration, and the resultant
      lethal zone created by a cryoprobe are critical for clinical application. To this
      end, cryoprobe performance is typically characterized based on the iceball size
      and temperature penetration in phantom gel models. Although informative, these
      models do not provide information as to the impact of heat input from surrounding
      tissue nor give any information on the ablative zone created. As such, we
      evaluated the use of a tissue-engineered tumor model (TEM) to assess cryoprobe
      performance including iceball size, real-time thermal profile distribution, and
      resultant ablative zone. Studies were conducted using an Endocare V-probe
      cryoprobe, with a 10/5/10 double freeze-thaw protocol using prostate and renal
      cancer TEMs. The data demonstrate the generation of a 33- to 38-cm3 frozen mass
      with the V-Probe cryoprobe following the double freeze of which ~12.7 and 6.5 cm3
      was at or below -20 degrees C and -40 degrees C, respectively. Analysis of
      ablation zone using fluorescence microscopy 24 hours postthaw demonstrated that
      the internal ~40% of the frozen mass was completely ablated, whereas in the
      periphery of the iceball (outer 1 cm region), a gradient of partial to minimal
      destruction was observed. These findings correlated well with clinical reports on
      renal and prostate cancer cryoablation. Overall, this study demonstrates that
      TEMs provide an effective model for a more complete characterization of
      cryoablation device performance. The data demonstrate that while the overall
      iceball size generated in the TEM was consistent with published reports from
      phantom models, the integration of an external heat load, circulation, and
      cellular components more closely reflect an in vivo setting and the impact of
      penetration of the critical (-20 degrees C and -40 degrees C) isotherms into the
      tissue. This is important as it is well appreciated in clinical practice that the
      heat load of a tissue, cryoprobe proximity to vasculature, and so on, can impact
      outcome. The TEM model provides a means of characterizing the impact on ablative
      dose delivery allowing for a better understanding of probe performance and
      potential impact on ablative outcome.

PMID- 28514900
TI  - A QM/QTAIM detailed look at the Watson-Crick<->wobble tautomeric transformations
      of the 2-aminopurine.pyrimidine mispairs.
AB  - This work is devoted to the careful QM/QTAIM analysis of the evolution of the
      basic physico-chemical parameters along the intrinsic reaction coordinate (IRC)
      of the biologically important 2AP.T(WC)<->2AP.T*(w) and 2AP.C*(WC)<->2AP.C(w)
      Watson-Crick(WC)<->wobble(w) tautomeric transformations obtained at each point of
      the IRC using original authors' methodology. Established profiles reflect the
      high similarity between the courses of these processes. Basing on the scrupulous
      analysis of the profiles of their geometric and electron-topological parameters,
      it was established that the dipole-active WC<->w tautomerizations of the Watson
      Crick-like 2AP.T(WC)/2AP.C*(WC) mispairs, stabilized by the two classical N3H?N1,
      N2H?O2 and one weak C6H?O4/N4 H-bonds, into the wobble 2AP.T*(w)/2AP.C(w) base
      pairs, respectively, joined by the two classical N2H?N3 and O4/N4H?N1 H-bonds,
      proceed via the concerted stepwise mechanism through the sequential intrapair
      proton transfer and subsequent large-scale shifting of the bases relative each
      other, through the planar, highly stable, zwitterionic transition states
      stabilized by the participation of the four H-bonds - N1+H?O4-/N4-, N1+H?N3-,
      N2+H?N3-, and N2+H?O2-. Moreover, it was found out that the 2AP.T(WC)<
      >2AP.T*(w)/2AP.C*(WC)<->2AP.C(w) tautomerization reactions occur non
      dissociatively and are accompanied by the consequent replacement of the 10 unique
      patterns of the specific intermolecular interactions along the IRC. Obtained data
      are of paramount importance in view of their possible application for the control
      and management of the proton transfer, e.g. by external electric or laser fields.

PMID- 28514901
TI  - Fixed-bed study for bone char adsorptive removal of refractory organics from
      electrodialysis concentrate produced by petroleum refinery.
AB  - Water reuse in industrial processes has been an increasing need encouraged in
      recent years. However, as the streams are recycled, solutes accumulate, thus
      requiring purification techniques. Membrane processes (reverse osmosis and
      electrodialysis) have been implemented and in order to increase the reuse of
      water at its highest level, crystallization has been evaluated to remove salts
      from the concentrate produced and get a feasible disposal. Nevertheless,
      contaminants affect the crystallization performance, thus making the removal of
      residual organics important for both the efficiency of crystallization and the
      increase of water reuse. In this context, aiming at establishing a sustainable
      virtuous circle, bone char (0.5-1.4 mm particle size, mesoporous structure) was
      used to remove refractory organics from an electrodialysis concentrate effluent
      (C-EDR) from a Brazilian petroleum refinery, at a lab-scale, in a fixed-bed
      adsorption column. Bone char selectively and partially removed the refractory
      organics, a complex mixture of long-chain hydrocarbons, aromatic compounds,
      carboxylic acids, amines and amides. The maximum adsorption capacity increased
      with the increase in bed depth and reduction in flow rate. A maximum removal of
      35.60 mg g-1 was achieved for the highest bed depth evaluated (12.9 cm). The
      breakthrough curves indicated that bone char could adsorb part of the organic
      compounds from the C-EDR. The scaling up was possible for the C/C0 ratios of
      0.55, 0.60 and 0.65, providing a service time at about 16 days for 45% removal
      efficiency for typical real operational conditions used in the refinery.

PMID- 28514902
TI  - Performance of modified anaerobic inclining-baffled reactor treating recycled
      paper mill effluent: effects of influent chemical oxygen demand concentration and
      hydraulic retention time.
AB  - The performance of modified anaerobic inclining-baffled reactor (MAI-BR) treating
      recycled paper mill effluent (RPME) was investigated by varying the influent
      chemical oxygen demand (CODin) concentration from 1000 to 4000 mg/L, and the
      hydraulic retention time (HRT) from 3 to 1 day, corresponding to an organic
      loading rate increase from 0.33 to 4 g COD/L day. Throughout 126 days of
      operation, a maximum removal efficiency of up to 96% of chemical oxygen demand
      (COD) and 99% of biological oxygen demand, methane (CH4) yield of 0.259 L CH4/g
      COD, and a stable effluent pH of 6.5 were achieved. Furthermore, the
      compartmental performance showed that most of the organic substrates were removed
      in the initial two compartments, resulting in low pH and alkalinity levels and a
      high concentration of volatile fatty acids. Overall, the results showed that the
      MAI-BR successfully treated RPME, and the performance was affected by the
      variation of HRT more than the CODin.

PMID- 28514903
TI  - Utility of the central motor conduction time recorded from the abductor pollicis
      brevis and the abductor digiti minimi muscles in patients with C6-7 myelopathy.
AB  - OBJECTIVE: Central motor conduction time (CMCT) recorded from the abductor
      pollicis brevis (CMCT-APB) and abductor digiti minimi (CMCT-ADM) muscles may
      enable the evaluation of patients with C6-7 myelopathy. CMCT is more useful for
      the evaluation of the function of spinal cord than magnetic resonance imaging
      (MRI) findings. CMCT may be associated with age and height. However, there are
      few reports regarding CMCT-APB in normal subjects. This study aimed to
      investigate the relationships between age, height, and conduction parameters in
      normal subjects to assess the effectiveness of using CMCT-APB and CMCT-ADM for
      the evaluation of patients with C6-7 and C7-T1 myelopathy. DESIGN: Retrospective
      study. METHODS: Fifteen patients with cervical compressive myelopathy at C6-7 (11
      patients) or C7-T1 (4 patients) level were enrolled. The control group consisted
      of 150 normal subjects (mean age 45.8+/-17.0 years; mean height 163.6+/-8.9 cm).
      Motor evoked potentials induced by transcranial magnetic stimulation and F-waves
      were used to determine CMCT. OUTCOME MEASURES: CMCT-APB, CMCT-ADM. RESULTS: The
      normative values of CMCT-APB and CMCT-ADM were 5.3+/-0.7 ms and 5.2+/-0.8 ms,
      respectively. CMCT-APB was significantly longer than CMCT-ADM for patients with
      C6-7 myelopathy (P < 0.05). Neither of the CMCTs for those with C7-T1 myelopathy
      were significantly different from those of controls, but CMCT-APB was more
      prolonged than CMCT-ADM in patients with C6-C7 myelopathy. CONCLUSIONS: CMCTs
      improve the accuracy of the diagnosis of myelopathy by pinpointing the lesion in
      combination with MRI imaging. Selective CMCT-APB prolongation may be seen in
      patients with C6-7 myelopathy but not C7-T1 myelopathy.

PMID- 28514905
TI  - Evodiamine Prevents Glioma Growth, Induces Glioblastoma Cell Apoptosis and Cell
      Cycle Arrest through JNK Activation.
AB  - Evodiamine (EVO) is an active medicinal compound derived from the traditional
      herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has
      several beneficial biological properties, including anticancer and anti
      inflammatory activities. However, the in vitro and in vivo anticancer activities
      of EVO against the growth of glioblastoma cells remain undefined. EVO induced
      significant decreases in the viability of U87 and C6 glioma cells, but not of
      primary astrocytes, according with the occurrence of apoptotic characteristics
      including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein
      cleavage, and hypodiploid cells. The disruption of the mitochondrial membrane
      potential (MMP) was detected, and it was found that the peptidyl caspase-9
      inhibitor, Z-LEHD-FMK, significantly prevented glioma cells from EVO-induced
      apoptosis. Increased c-Jun N-terminal kinase (JNK) protein phosphorylation by EVO
      was observed, and the addition of JNK inhibitors, SP600125 and JNKI inhibited the
      EVO-induced apoptosis was inhibited. Additionally, EVO treatment induced G2/M
      arrest with increased polymerized tubulin protein expression in U87 and C6 cells.
      Elevated expressions of the cyclin B1, p53, and phosphorylated (p)-p53 proteins
      were detected in EVO-treated glioma cells, and these were inhibited by JNK
      inhibitors. An in vivo study showed that EVO significantly reduced the growth of
      gliomas elicited by the subcutaneous injection of U87 cells with increases in
      cyclin B1, p53, and p-p53 protein expressions in tumors. An analysis of eight EVO
      related chemicals showed that alkyl groups at position 14 in EVO are important
      for its anti-glioma effects which involve both apoptosis and G2/M arrest.
      Evidence is provided that supports EVO induction of apoptosis and G2/M arrest via
      the activation of JNK-mediated gene expression and disruption of MMP in
      glioblastoma cells. EVO was shown to penetrate the blood-brain barrier; EVO is
      therefore predicted to be a promising compound for the chemotherapy of
      glioblastomas and deserves further investigations.

PMID- 28514904
TI  - Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in
      ApoE[Formula: see text] via the AMPK Pathway.
AB  - Atherosclerosis was previously thought to be a disease that primarily involves
      lipid accumulation in the arterial wall. In this report, we investigated the
      effect of Viola mandshurica W. Becker (V. mandshurica) water extract on
      atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The
      administration of V. mandshurica to high-fat diet-fed mice reduced body weight,
      liver weight, and serum levels of lipids (total cholesterol, low-density
      lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and
      aspartate transaminase. Histopathologic analyses of the aorta and liver revealed
      that V. mandshurica attenuated atherosclerotic lesions and reduced lipid
      accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica
      also increased phosphorylation of adenosine monophosphate-activated protein
      kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and
      inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V.
      mandshurica reduced protein expression levels of adhesion molecules
      (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E
      selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition,
      quantitative analysis of V. mandshurica by high-performance liquid chromatography
      revealed the presence of esculetin and scopoletin. Esculetin and scopoletin
      reduced adhesion molecules in human aortic smooth muscle cells. Our results
      indicate that the anti-atherosclerotic effects of V. mandshurica may be
      associated with activation of the AMPK pathway. Therefore, AMPK-dependent
      phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic
      strategy for combatting atherosclerosis and hepatic steatosis.

PMID- 28514906
TI  - The Effects of Gymnema sylvestre in High-Fat Diet-Induced Metabolic Disorders.
AB  - This study used an integrated approach to investigate the effects of Gymnema
      sylvestre (GS) extract as a functional dietary supplement with a high-fat diet.
      This approach examined insulin resistance, the dysfunction of adipose tissue, and
      liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD)
      for the acute and chronic study, in addition to GS in different doses (100, 250
      and 500[Formula: see text]mg/kg body weight). Their body composition changes,
      serum lipid and glucose parameters, adipose and liver tissue histology, and gene
      expression were measured. It was found that GS significantly suppressed the
      increase of body weight, serum levels of lipid, insulin and leptin, and adipose
      tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to
      the amylase inhibition activity. Our results support the existence of a
      relationship between the HFD induced insulin resistance, adipose dysfunction and
      liver steatosis. In conclusion, GS works as a functional dietary supplement with
      preventative effects against metabolic disorder.

PMID- 28514907
TI  - Nudging for Prevention in Occupational Health and Safety in South Africa Using
      Fiscal Policies.
AB  - Currently, in some countries occupational health and safety policy and practice
      have a bias toward secondary prevention and workers' compensation rather than
      primary prevention. Particularly, in emerging economies, research has not
      adequately contributed to effective interventions and improvements in workers'
      health. This article, using South Africa as a case study, describes a methodology
      for identifying candidate fiscal policy interventions and describes the policy
      interventions selected for occupational health and safety. It is argued that
      fiscal policies are well placed to deal with complex intersectoral health
      problems and to focus efforts on primary prevention. A major challenge is the
      lack of empirical evidence to support the effectiveness of fiscal policies in
      improving workers' health. A second challenge is the underprioritization of
      occupational health and safety partly due to the relatively small burden of
      disease attributed to occupational exposures. Both challenges can and should be
      overcome by (i) conducting policy-relevant research to fill the empirical gaps
      and (ii) reconceptualizing, both for policy and research purposes, the role of
      work as a determinant of population health. Fiscal policies to prevent exposure
      to hazards at work have face validity and are thus appealing, not as a
      replacement for other efforts to improve health, but as part of a comprehensive
      effort toward prevention.

PMID- 28514908
TI  - Using action learning sets to support change in end-of-life care.
AB  - Purpose The purpose of this paper is to describe the delivery of facilitated
      action learning sets as an integral component of a multidisciplinary end-of-life
      care course. Design/methodology/approach The educational intervention described
      in this paper is delivered by specialist palliative care practitioners to those
      working with dying patients and their families in non-specialist settings. The
      programme consists of two components: the first taught/experience-based component
      takes place in a hospice. The second integral component involves action learning
      sets which are facilitated by specialist palliative care staff over a six-month
      period. This paper reports the challenges, learning and benefits of using action
      learning sets to improve end-of-life care. Findings Action learning sets provide
      support which enables staff to implement changes to end-of-life care.
      Participants in the successful action learning sets were motivated to change
      practice and identified themselves as change agents. Management support was vital
      to allow participants the authority to implement changes to practice. Practical
      implications Facilitators need to gain participant and management commitment to
      the action learning process before the programme begins if they are to be
      successful in achieving changes to end-of-life care. Originality/value Hospices
      and other health care organisations work in partnership to deliver this
      programme, and this paper demonstrates how action learning sets can increase
      mutual understanding and communication between specialist and non-specialist end
      of-life care settings.

PMID- 28514909
TI  - What can action learning offer a beleaguered system? A narrative representing the
      relationship.
AB  - Purpose This is an attempt to write an account of action learning that is as
      close to the ground on which it was practised as the author can make it. In that
      sense, the reader can read what follows below as a kind of autoethnography, a
      "representation as relationship" as Gergen and Gergen (2002, p. 11) call it. This
      is because in the opportunity of telling a story about his practice as an action
      learning facilitator, the author hopes to evoke that which is more akin to the
      contactful environment of quality action learning than any amount of abstract
      theorising. Design/methodology/approach This is an example of "narrative
      inquiry", best judged, according to Sparkes (2002), in terms of the ability of
      such accounts to "contribute to sociological understanding in ways that, amongst
      others are self-knowing, self-respecting, self-sacrificing and self-luminous".
      Findings As the author re-tells this partial account, he has a sense of the
      massive wider structures around him, but all he can see in his dim lamp is the
      fleeting glimpse of the local strata. The author traces his hand along the seams,
      not intending to dig them out, but simply to witness them, or even, in a spirit
      of yearning, to give them a witnessing of themselves. Originality/value To the
      author, this is about portraying what action learning feels like, rather than
      thinks like, for his own and for the benefit of other practitioners.

PMID- 28514910
TI  - Value-based healthcare measurement as a context for organizational learning.
AB  - Purpose The purpose of this paper is to shed light on the potential of
      organizational learning for developing effectiveness of care. Value-based
      healthcare measurement recognizes patient value as a driver for improving health
      outcomes at the societal and individual levels. By using the action learning
      method, this paper examines the phases of organizational learning in a private
      healthcare organization that has developed a novel Big Data screening tool for
      the treatment of patients with type 2 diabetes mellitus (DM2).
      Design/methodology/approach Relying on triple-loop learning as a conceptual
      framework and by applying the action learning method to case study design, this
      paper illustrates the phases of organizational learning and efforts to utilize
      value-based measurement in healthcare. Findings The case organization was able to
      identify patients at risk and to improve their care balance. Although the results
      for the measurement of patient outcomes led to questioning of previous care
      processes and practices in the organization, increasing value for all
      stakeholders by incorporating social needs to business opportunities remains
      under process. Originality/value With the focus on organizational learning and
      organizational value creation processes, this paper demonstrates incorporation of
      measuring patient outcomes in re-structuring care processes, enhancing
      organizational performance and improving effectiveness as well as quality of
      care.

PMID- 28514911
TI  - Action learning across the decades.
AB  - Purpose The purpose of this paper is to explore how action learning concepts were
      used in two healthcare projects undertaken many decades apart. The specific
      purpose in both cases was to examine how action learning can contribute to shared
      learning across key stakeholders in a complex socio-technical system. In each
      case study, action learning supported joint design programmes and the sharing of
      perspectives about the complex system under investigation.
      Design/methodology/approach Two action learning projects are described: first,
      the Hospital Internal Communications (HIC) project led by Reg Revans in the
      1960s. Senior staff in ten London hospitals formed action learning teams to
      address communication issues. Second, in the Better Outcomes for People with
      Learning Disabilities: Transforming Care (BOLDTC) project, videoconferencing
      equipment enabled people with learning disabilities to increase their
      opportunities to communicate. A mutual learning process was established to enable
      stakeholders to explore the potential of the technical system to improve
      individual care. Findings The HIC project demonstrated the importance of evidence
      being shared between team members and that action had to engage the larger
      healthcare system outside the hospital. The BOLDTC project confirmed the
      continuing relevance of action learning to healthcare today. Mutual learning was
      achieved between health and social care specialists and technologists.
      Originality/value This work draws together the socio-technical systems tradition
      (considering both social and technical issues in organisations) and action
      learning to demonstrate that complex systems development needs to be undertaken
      as a learning process in which action provides the fuel for learning and design.

PMID- 28514912
TI  - Team sponsors in community-based health leadership programs.
AB  - Purpose The purpose of this article is to share the lessons learned about the
      role of team sponsors in action-learning teams as part of community-based health
      leadership development programs. Design/methodology/approach This case study uses
      program survey results from fellow participants, action learning coaches and team
      sponsors to understand the value of sponsors to the teams, the roles they most
      often filled and the challenges they faced as team sponsors. Findings The extent
      to which the sponsors were perceived as having contributed to the work of the
      action learning teams varied greatly from team to team. Most sponsors agreed that
      they were well informed about their role. The roles sponsors most frequently
      played were to provide the teams with input and support, serve as a liaison to
      the community and serve as a sounding board, motivator and cheerleader. The most
      common challenges or barriers team sponsors faced in this role were keeping
      engaged in the process, adjusting to the role and feeling disconnected from the
      program. Practical implications This work provides insights for program
      developers and community foundations who are interested in building the capacity
      for health leadership by linking community sponsors with emerging leaders engaged
      in an action learning experience. Originality/value This work begins to fill a
      gap in the literature. The role of team sponsors has been studied for single
      organization work teams but there is a void of understanding about the role of
      sponsors with multi-organizational teams working to improve health while also
      learning about leadership.

PMID- 28514913
TI  - Action learning: ripples within and beyond the set.
AB  - Purpose This paper aims to explore the impact of action learning (AL) on an
      individual and an organisation, particularly the process by which each affected
      the other. The organisation is a UK National Health Service (NHS) Trust that
      includes two hospitals. Design/methodology/approach This is a single person case
      study involving a clinician, but the voice of an author can also be heard. It
      involves the experience of the individual as they experience AL as part of a
      leadership development programme leading to a postgraduate certificate. The
      authors explain their caution of the case study approach and in doing so offer
      their thoughts in how this paper could be read and impact on practice. Findings
      The authors show a process whereby an AL set participant moves from being
      confident about their project to one of uncertainty as the impact of the project
      ripples throughout the organisation. Through this process of unsettlement, the
      individual's unnoticed assumptions are explored in ways that enable practical
      action to be taken. In doing so, the individual's leadership and identity
      developed. Research limitations/implications This is a single person case study
      in one organisation, thus affecting wider generalisation. Originality/value This
      single case study contributes to the debate on critical AL and the use of AL in
      the NHS.

PMID- 28514914
TI  - Using action learning to reduce health inequity in Danish municipalities.
AB  - Purpose The aim of this study is to clarify how action learning can be used as a
      vehicle for promoting equal access to municipal health services for socially
      disadvantaged groups in a Danish context. It is the purpose of this paper to
      describe the methods for reducing health inequity developed in the study and to
      discuss how action learning methodologically contributed to achieving these
      results. Design/methodology/approach In the study, the front-line staff from 19
      health and social service units in six different municipalities, in Denmark, each
      formed an action learning group to develop methods for reducing health inequity
      in a municipal health setting. Each group was guided by an external facilitator,
      according to an Action Learning Action Research phase model (ALAR-model), which
      structured the cyclical development of methods into four phases: diagnosing,
      planning action, taking action and evaluating action. Findings Two types of
      results of the study are reported in the paper. First, the authors present an
      overview of the results the 19 participating municipal units have achieved in
      their action learning processes, as well as two case examples of how two units
      have worked with action learning and the concrete methods and tools they have
      developed in this process. Second, they report the challenges and dilemmas the 19
      units faced when working with action learning in the study. Originality/value
      With its use of action learning techniques and the ALAR-model, this study
      contributes to the development of practice-based methods to reduce unequal access
      to municipal health services for socially disadvantaged groups. Through the
      study, the front-line staff in the health and social service units has been
      involved in the problem-solving process, to a much greater extent than it has
      previously been adopted in a Danish municipal health setting.

PMID- 28514915
TI  - Foreword.

PMID- 28514916
TI  - Guest editorial.

PMID- 28514917
TI  - Advancing health care quality and safety through action learning.
AB  - Purpose The purpose of this study is to demonstrate how action learning can be
      practically applied to quality and safety challenges at a large academic medical
      health system and become fundamentally integrated with an institution's broader
      approach to quality and safety. Design/methodology/approach The authors describe
      how the fundamental principles of action learning have been applied to advancing
      quality and safety in health care at a large academic medical institution. The
      authors provide an academic contextualization of action learning in health care
      and then transition to how this concept can be practically applied to quality and
      safety by providing detailing examples at the unit, cross-functional and
      executive levels. Findings The authors describe three unique approaches to
      applying action learning in the comprehensive unit-based safety program, clinical
      communities and the quality management infrastructure. These examples,
      individually, provide discrete ways to integrate action learning in the
      advancement of quality and safety. However, more importantly when combined, they
      represent how action learning can form the basis of a learning health system
      around quality and safety. Originality/value This study represents the broadest
      description of action learning applied to the quality and safety literature in
      health care and provides detailed examples of its use in a real-world context.

PMID- 28514918
TI  - Does vitamin D deficiency affect placental inflammation or infections among very
      low birth weight infants?
AB  - OBJECTIVE: Examine the association between placental inflammation and neonatal
      infections, and 25OH vitamin D (25OH D) levels at birth among very low birth
      weight infants (VLBWI). STUDY DESIGN: Serum 25OH D levels were measured in 89
      VLBWI (<=1250 g) and 47 mothers on day one, and in 78 infants on day 21.
      Placentas were examined for maternal and fetal inflammation. Infants were divided
      into deficient (<=10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D
      levels on day 1. RESULTS: Mean +/- SD maternal levels of 25OH D (21 +/- 9 ng/ml)
      correlated with infants' levels (15 +/- 8 ng/ml), (p < .001). 25OH D levels were
      lower in deficient (32/89) than in adequate group (8 +/- 2 versus 20 +/- 7 ng/ml,
      p = .011). Infants' 25OH D levels rose significantly by day 21 (p < .001).
      Univariate analyses showed no differences between infant groups in maternal or
      fetal inflammation, or neonatal infections (p > .05). Logistic regression
      analyses revealed no association between deficient 25OH D levels and the odds of
      maternal or fetal inflammation or other infections. Levels of 25OH D did not
      correlate with severity of placental inflammation. CONCLUSIONS: Deficient levels
      of 25OH D at birth are not associated with the occurrence of placental
      inflammation or neonatal infections among VLBWI.

PMID- 28514919
TI  - Periconceptional CMV infection prevention in Portugal: population subgroup study
      in a tertiary perinatal care center.
AB  - Currently in Portugal, universal screening of pregnant women for Cytomegalovirus
      (CMV) infection is not performed. However, it is recommended to screen all women
      attending preconception care. We aimed to assess women's attendance to
      preconception care and if their serologic status regarding CMV was known and/or
      investigated in that consultation. In this cross-sectional study, we interviewed
      240 women admitted to the obstetrical ward of a hospital in the Metropolitan Area
      of Porto (Portugal) about their adherence to preconception care and collected
      data regarding their CMV serologic status and its investigation. We found that
      71.3% of the women who attended preconception care were not screened for CMV
      infection. Among primigravida, the screening rate was only of 30.4% (upper limit
      of CI 95%: 44.8%). There were no statistically significant differences between
      the private and public sectors of healthcare. We observed attendance to
      preconception care is high (73.1%). For the population subgroup of the
      metropolitan area of Porto, attendance to preconception care is at least 66%,
      with a 95% confidence level. Portuguese guidelines stating a woman's serologic
      status regarding CMV should be investigated in preconception care are not
      properly implemented. This suggests guidelines should assure the screening of
      previously non-screened women during pregnancy.

PMID- 28514920
TI  - Predicting Factors of Zone 4 Attack in Volleyball.
AB  - This study examined 142 volleyball games of the Men's Super League 2014/2015
      seasons in Brazil from which we analyzed 24-26 games of each participating team,
      identifying 5,267 Zone 4 attacks for further analysis. Within these Zone 4
      attacks, we analyzed the association between the effect of the attack carried out
      and the separate effects of serve reception, tempo and type of attack. We found
      that the reception, tempo of attack, second tempo of attack, and power of
      diagonal attack were predictors of the attack effect in Zone 4. Moreover, placed
      attacks showed a tendency to not yield a score. In conclusion, winning points in
      high-level men's volleyball requires excellent receptions, a fast attack tempo
      and powerfully executed of attacks.

PMID- 28514921
TI  - A Study of Relationships among Technical, Tactical, Physical Parameters and Final
      Outcomes in Elite Soccer Matches as Analyzed by a Semiautomatic Video Tracking
      System.
AB  - The performance of a soccer team depends on many factors such as decision-making,
      cognitive and physical skills, and dynamic ever-changing space-time interactions
      between teammate and opponents in relation to the ball. Seventy ( n = 70) matches
      of the Italian SERIE A season 2013-2014 were investigated to analyze the mean
      performance of 360 players in terms of physical (physical efficiency index; PEI)
      and technical-tactical (technical efficiency index; TEI) standpoints. Using a
      semiautomatic video analysis system that has incorporated new parameters able to
      measure technical-tactical and physical efficiency (Patent IB2010/002593, 2011
      ISA), the correlation between these new variables and how much it relates to the
      likelihood of winning were verified. Correlations between TEI and PEI were
      significant ( n = 140, r = .60, p < .001), and TEI showed a higher likelihood of
      winning than PEI factors ( p < .0001 vs. .0001, CI 95% [1.64, 3.00] vs. [1.28,
      2.07]). Higher TEI and TEI + PEI differences between the teams were associated
      with a greater likelihood of winning, but PEI differences were not. Key
      performance indicators and this performance assessment method might be useful to
      better understand what determines winning and to assist the overall training
      process and match management.

PMID- 28514922
TI  - Effects of Youth Participation in Extra-Curricular Sport Programs on Perceived
      Self-Efficacy: A Multilevel Analysis.
AB  - The present study examined extracurricular sport participation variables and
      developmental context in relationship to perceived self-efficacy among
      underserved adolescents. Participants ( n = 821, 13.6 +/- 1.5 years) completed
      the Youth Experience in Sport questionnaire and General Self-Efficacy Scale. We
      used the Human Development Index (HDI) to characterize developmental contexts.
      Multilevel regression models were used to explore the relative contributions of
      age, sex, years of participation in extracurricular sport, HDI, and perceived
      positive experience in sport. Our results highlight that positive experience
      alone and in interaction with length of participation in the program fostered
      perceived self-efficacy. Participants from higher HDI contexts remained longer in
      the program. An implication of our research is that variables linked to positive
      sport experiences and perceived self-efficacy can be used as markers to evaluate
      the outcomes and impact of sport participation programs aimed at promoting
      positive youth development.

PMID- 28514923
TI  - Object-Spatial Imagery and Verbal Cognitive Styles in High School Students.
AB  - The present study investigated object-spatial imagery and verbal cognitive styles
      in high school students. We analyzed the relationships between cognitive styles,
      object imagery ability, spatial visualization ability, verbal-logical reasoning
      ability, and preferred modes of processing math information. Data were collected
      from 348 students at six high schools in two school districts. Spatial imagery
      style was not correlated with object imagery style and was negatively correlated
      with verbal style. Object imagery style did not correlate significantly with any
      cognitive ability measure, whereas spatial imagery style significantly correlated
      with object imagery ability, spatial visualization ability, and verbal-logical
      reasoning ability. Lastly, spatial imagery style and verbal-logical reasoning
      ability significantly predicted students' preference for efficient visual
      methods. The results support the cognitive style model, in which visualizers are
      characterized as two distinct groups who process visual-spatial information and
      graphic tasks in different ways.

PMID- 28514924
TI  - Rapid and annealing-free self-assembly of DNA building blocks for 3D hydrogel
      chaperoned by cationic comb-type copolymers.
AB  - The construction and self-assembly of DNA building blocks are the foundation of
      bottom-up development of three-dimensional DNA nanostructures or hydrogels.
      However, most self-assembly from DNA components is impeded by the mishybridized
      intermediates or the thermodynamic instability. To enable rapid production of
      complicated DNA objects with high yields no need for annealing process, herein
      different DNA building blocks (Y-shaped, L- and L'-shaped units) were assembled
      in presence of a cationic comb-type copolymer, poly (L-lysine)-graft-dextran (PLL
      g-Dex), under physiological conditions. The results demonstrated that PLL-g-Dex
      not only significantly promoted the self-assembly of DNA blocks with high
      efficiency, but also stabilized the assembled multi-level structures especially
      for promoting the complicated 3D DNA hydrogel formation. This study develops a
      novel strategy for rapid and high-yield production of DNA hydrogel even derived
      from instable building blocks at relatively low DNA concentrations, which would
      endow DNA nanotechnology for more practical applications.

PMID- 28514925
TI  - Factors affecting cell-free DNA fetal fraction and the consequences for test
      accuracy.
AB  - INTRODUCTION: Biological factors are known to influence the fetal fraction (FF)
      of cell-free DNA and may also influence the accuracy of non-invasive prenatal
      testing. MATERIAL AND METHODS: NIPT from 5267 mixed risk women across three
      specialist clinics in Australia were analyzed. Multivariable regression analysis
      was used to determine whether maternal characteristics, ultrasound, and placental
      biomarkers affect FF and test accuracy. RESULTS: FF ranged from 4% to 37% (mean
      11.6%). Body mass index (BMI), gestation, and placental biomarkers were found to
      be significant factors associated with FF. For each unit increase in BMI, the
      logarithmically transformed FF, (lnFF), mean value decreased by 0.027. Each week
      increases in gestation, lnFF increased by 0.023. Each unit increase in free BhCG,
      PAPPA, and PlGF, the lnFF increased by 0.065, 0.050, and 0.17, respectively.
      There was no significant association between FF with either maternal age or
      nuchal translucency. The false-positive cases and one false-negative case did not
      have lower FF than the true-positive cases. DISCUSSION: The fetal fraction in
      maternal plasma cfDNA increased with gestational age, serum pregnancy-associated
      plasma protein A (PAPP-A), beta-hCG, and PlGF and decreased with increasing
      maternal BMI. There was no significant correlation between low FF and test
      accuracy, when FF was above 4%.

PMID- 28514927
TI  - La vida normal: living with HIV in Santo Domingo, Dominican Republic.
AB  - In this study, we explore how individuals living with HIV in the Dominican
      Republic strive to live a 'normal' life and the consequences of this pursuit of
      normalcy. We conducted qualitative in-depth interviews with men (n = 20) and
      women (n = 20) living with HIV and receiving care at two urban clinics in Santo
      Domingo. We analysed the data using a combination of narrative analysis and
      thematic coding. We aimed to identify how fears and/or lived experiences with
      social rejection and HIV-related stigma and discrimination shaped participants'
      abilities to maintain social relationships, be economically productive and manage
      HIV within the context of sexual relationships. Participants used the discourse
      of una vida normal (a normal life) to frame their response to HIV. This pursuit
      of normality was driven by the social and economic pressures of living with a
      chronic condition in a context of HIV-related stigma; trying to keep things
      'normal' further added to these pressures. We argue that the normal life
      discourse fails to recognise the dynamic and complex nature of negotiating this
      condition and may also create additional burdens for individuals living with HIV
      that could impact their wellbeing and preventive behaviours.

PMID- 28514926
TI  - Trunk muscle activity patterns and motion patterns of patients with motor
      complete spinal cord injury at T8 and T10 walking with different un-powered
      exoskeletons.
AB  - OBJECTIVE: The aim of this study was to explore how neurological injured levels
      of spinal cord affect the performance of patients walking with different un
      powered exoskeletons. STUDY DESIGN: Case series observational study. SETTING:
      Gait and Motion Analysis Laboratory at the National Research Center
      Rehabilitation Technical Aids. METHODS: Electromyography and motion data from two
      subjects with complete spinal cord injury at T10 and T8 walking with un-powered
      exoskeletons were collected simultaneously. OUTCOME MEASURES: Surface
      electromyography of trunk muscles and motion data including joint angle and
      center of mass (COM). RESULTS: Compared to T10 subject, T8 subject activated
      trunk muscles in higher levels walking with all tested un-powered exoskeletons
      and had greater pelvic obliquity walking with reciprocating gait orthosis (RGO)
      and energy-stored exoskeleton (ES-EXO). ES-EXO can redistribute muscle forces,
      recruit trunk muscles evenly, increase walking speed and improve COM trajectory
      in frontal plane. CONCLUSION: This study revealed differences in kinematics and
      muscle activities in walking with three un-powered exoskeletons between two
      patients with different neurological injured levels. ES-EXO had advantages over
      conventional un-powered exoskeletons on recruiting muscles evenly and improving
      walking speed, step length and COM trajectory.

PMID- 28514928
TI  - Challenges in evaluation of screening for gastric cancer among men based on
      nonrandomized design.
AB  - BACKGROUND: Objective was to quantify biases in screening for gastric cancer when
      comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as
      primary test. METHODS: In mid 1990s, all men aged 51-65 years from two Finnish
      cities were invited to SPGI screening. Mortality and premature mortality in
      attenders were compared to nonattenders. Efficacy of screening was studied by 15
      years' follow-up of standardized mortality ratio (SMR) and potential years of
      life lost (PYLL) due to gastric cancer. Bias due to selective attendance was
      quantified using corrective coefficients based on total cancer incidence and
      mortality, and gastric cancer-specific incidence and mortality for total
      population and nonattenders. RESULTS: In 1994-1996, men aged 51-65 years (16,872)
      were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or
      less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening
      gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were
      referred for treatment due to abnormal focal lesions. Attributable proportions in
      reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%.
      After correcting for selective participation, attributable proportions were
      reduced to 23% and 39%. CONCLUSIONS: Biomarker screening by low SPGI among middle
      aged men followed by upper gastrointestinal endoscopy decreased long-term and
      premature mortality due to gastric cancer. However, in spite of methodological
      corrections done, the results do not justify any firm conclusions or recommend
      general screening programs. Randomized trials are warranted for this purpose.

PMID- 28514929
TI  - Five-year outcomes from a prospective trial of image-guided accelerated
      hypofractionated proton therapy for prostate cancer.
AB  - PURPOSE: To report 5-year outcomes of a prospective trial of image-guided
      accelerated hypofractionated proton therapy (AHPT) for prostate cancer. PATIENTS
      AND METHODS: 215 prostate cancer patients accrued to a prospective institutional
      review board-approved trial of 70Gy(RBE) in 28 fractions for low-risk disease (n
      = 120) and 72.5Gy(RBE) in 29 fractions for intermediate-risk disease (n = 95).
      This trial excluded patients with prostate volumes of >=60 cm3 or International
      Prostate Symptom Scores (IPSS) of >=15, patients on anticoagulants or alpha
      blockers, and patients in whom dose-constraint goals for organs at risk (OAR)
      could not be met. Toxicities were graded prospectively according to Common
      Terminology Criteria for Adverse Events (CTCAE), version 3.0. This trial can be
      found on ClinicalTrials.gov (NCT00693238). RESULTS: Median follow-up was 5.2
      years. Five-year rates of freedom from biochemical and clinical disease
      progression were 95.9%, 98.3%, and 92.7% in the overall group and the low- and
      intermediate-risk subsets, respectively. Actuarial 5-year rates of late radiation
      related CTCAE v3.0 grade 3 or higher gastrointestinal and urologic toxicities
      were 0.5% and 1.7%, respectively. Median IPSS before treatment and at 4+ years
      after treatment were 6 and 5 for low-risk patients and 4 and 6 for intermediate
      risk patients. CONCLUSIONS: Image-guided AHPT 5-year outcomes show high efficacy
      and minimal physician-assessed toxicity in selected patients. These results are
      comparable to the 5-year results of our prospective trials of standard
      fractionated proton therapy for patients with low-risk and intermediate-risk
      prostate cancer. Longer follow-up and a larger cohort are necessary to confirm
      these findings.

PMID- 28514930
TI  - Hypofractionated stereotactic body radiotherapy for localized prostate cancer -
      first Nordic clinical experience.
AB  - BACKGROUND: The use of hypofractionated stereotactic body radiotherapy (SBRT) as
      primary treatment modality in clinically localized prostate cancer (PCa) is
      emerging, because the low alpha/beta-ratio favors the use of high dose per
      fraction in PCa. There is a need for more data about SBRT, especially in high
      risk PCa patients. The purpose of this retrospective study was to evaluate the
      safety and the short-term efficacy of robotic SBRT in a clinical patient cohort
      with localized PCa including also high-risk patients (D'Amico risk
      stratification). MATERIALS AND METHODS: A total of 240 consecutive patients with
      clinically localized PCa were treated primarily with SBRT to total doses of 35 Gy
      or 36.25 Gy in 5 fractions using a robotic SBRT device (CyberKnife(r)). All risk
      groups (D'Amico risk stratification) were represented as follows: 48 (22%), 59
      (27%) and 111 (51%) of the patients representing low-, intermediate- and high
      risk group, respectively. Data on acute and intermediate-term toxicities and
      early PSA responses were analyzed. RESULTS: Neither acute grade 3 or higher GU
      nor rectal toxicity was observed. Regardless of the fact that 29 (13.3%) patients
      experienced intermediate-term toxicity requiring diagnostic interventions, the
      rates of intermediate-term grade 3 GU, rectal and infectious toxicity were low,
      1.8%, 0.9% and 1.4%, respectively. A biochemical relapse was observed in ten
      (4.6%) patients. With the median follow-up time of 23 months the biochemical
      relapse-free survival (bRFS) rate was 100%, 96.6% and 92.8% in low-, intermediate
      and high-risk group, respectively. CONCLUSIONS: The toxicity of robotic SBRT in
      a large clinical cohort of PCa patients was tolerable and the early PSA response
      was good in all risk groups. The hypofractionated SBRT offers a possibility to
      high dose per fraction and to provide the whole radiotherapy treatment within two
      to three weeks.

PMID- 28514931
TI  - Lung cancer in never-smokers - what are the differences?
AB  - INTRODUCTION: Characteristics of never-smokers with lung cancer are still not
      fully clarified. The aim of this study was to compare never-smokers and ever
      smokers with non-small cell lung cancer (NSCLC) regarding patient and tumor
      characteristics. METHODS: All consecutive newly NSCLC patients with known smoking
      status diagnosed between 2011 and 2015 were included in this retrospective cohort
      study. Clinical, histological, and molecular characteristics were compared
      between ever-smokers and never-smokers. RESULTS: Of the 558 included patients,
      125 (22.4%) were never-smokers. These patients were more likely to be female (74%
      vs. 7%, p < .001), older (67 vs. 66 years-old, p = .019), and have adenocarcinoma
      (93% vs. 65%, p < .001). Never-smokers took longer to seek medical care after the
      symptoms onset (3 vs. 2 months, p < .001), regardless of the symptoms,
      histological type, or gender (OR: 1.2 [1.4-2.0]). The metastatic pattern was
      different in never-smokers: pleural metastases were more frequent (OR: 2.1 [1.1
      4.0]), regardless of the histological type and gender. Never-smokers had a higher
      prevalence of ALK translocations (26% vs. 4%, p < .001) and EGFR mutations (36%
      vs. 8%, p < .001). The type of EGFR mutation was also significantly different
      between groups. CONCLUSIONS: Never-smokers with NSCLC present distinct
      demographic and clinical characteristics. The characteristics of tumor also
      differ between never-smokers and ever-smokers, which may suggest different
      carcinogenic pathways.

PMID- 28514932
TI  - Case report of severe maternal hyponatremia complicating preeclampsia.
AB  - The incidence of preeclampsia associated maternal and neonatal hyponatremia is
      reportedly rare and can be life threatening in severe cases. The timely diagnosis
      and careful management requires a multidisciplinary approach between obstetric,
      neonatal, endocrinology, and intensive care teams. We report firstly, on a case
      of severe hyponatremia associated with preeclampsia, secondary to inappropriate
      Anti-Diuretic Hormone secretion, followed by a review of cases over a one year
      period at our institution.

PMID- 28514933
TI  - Obituary notice: Dr John Moll.

PMID- 28514934
TI  - A hypothesis: King Henry VIII's (1491-1547) personality change: A case of lead
      poisoning?
AB  - Henry VIII (1491-1547) became King of England in 1509. He started out as a good
      monarch, sensible, reasonable and pleasant, but later his behaviour changed
      drastically. He became irascible, intolerant, violent and tyrannical. In January
      1536, Henry had a serious jousting accident and was unconscious for 2 h. It is
      generally believed that this accident played a major role in his personality
      change. Letters of that time, however, indicate that the change began insidiously
      in 1534 and became most drastic in 1535, a year before the accident. Henry had
      suffered from leg ulcers before and after the accident and had been constantly
      treated for them for many years. Sloane MS1047, now in the British Library in
      London, contains the prescriptions for the medications used to treat these
      ulcers. Many of the medications contain a high proportion of lead in various
      forms. Lead can be absorbed through skin, especially damaged skin. Absorbed lead
      can affect the brain, causing psychiatric problems, especially those associated
      with violence. The author presents a hypothesis that absorbed lead from his
      medications might have been a major factor in King Henry's personality change.

PMID- 28514935
TI  - Mesenchymal Stem Cell-Based Cartilage Regeneration Approach and Cell Senescence:
      Can We Manipulate Cell Aging and Function?
AB  - Aging is the most prominent risk factor triggering several degenerative diseases,
      such as osteoarthritis (OA). Due to its poor self-healing capacity, once injured
      cartilage needs to be reestablished. This process might be approached through
      resorting to cell-based therapies and/or tissue engineering. Human mesenchymal
      stem cells (MSCs) represent a promising approach due to their chondrogenic
      differentiation potential. Presently, in vitro chondrogenic differentiation of
      MSCs is limited by two main reasons as follows: aging of MSCs, which determines
      the loss of cell proliferative and differentiation capacity and MSC-derived
      chondrocyte hypertrophic differentiation, which limits the use of these cells in
      cartilage tissue regeneration approach. The effect of aging on MSCs is
      fundamental for stem cell-based therapy development, especially in older
      subjects. In the present review we focus on homeostasis alterations occurring in
      MSC-derived chondrocytes during in vitro aging. Moreover, we deal with potential
      cell aging regulation approaches, such as cell stimulation through telomerase
      activators, mechanical strain, and epigenetic regulation. Future investigations
      in this field might provide new insights into innovative strategies for cartilage
      regeneration and potentially inspire novel therapeutic approaches for OA
      treatment.

PMID- 28514936
TI  - Evaluation of an indirect oscillometric blood pressure monitor in anaesthetised
      dogs at three different anatomical locations.
AB  - AIMS: To evaluate the agreement between invasive and non-invasive measurements of
      blood pressure (BP) using an oscillometer (PetTrust) at three different
      anatomical locations in anaesthetised dogs under different haemodynamic
      conditions. METHODS: Eight adult Greyhounds weighing 23.5-36.5 kg were
      anaesthetised with isoflurane and positioned in dorsal recumbency. Systolic
      arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial
      pressure (MAP) were measured invasively via a dorsal pedal artery and non
      invasively using the oscillometer with cuffs placed above the carpus, above the
      tarsus and around the tail base. Phenylephrine was administered to induce
      vasoconstriction, dobutamine was used to increase cardiac output and increased
      end-tidal concentrations of isoflurane were used to induce vasodilation.
      Correlation between measurements was analysed by linear regression and agreement
      was analysed using Bland-Altman plots. RESULTS: Seventy two representative
      measurements were obtained. Mean differences (bias) between invasive and non
      invasive measurements were <5 mmHg except for DAP measured on the tail, and SD
      (precision) were <15 mm Hg except for SAP measured at the pelvic limb.
      Correlation coefficients were >0.9 except for SAP on the pelvic limb and DAP on
      the tail. More than 50 and 80% of values measured using oscillometry lay within
      10 and 20 mmHg, respectively, of values measured invasively except for SAP on the
      tail. SAP tended to be overestimated when measured non-invasively at low BP, and
      be underestimated at high BP. DAP was underestimated during low BP and
      overestimated during high BP. Hypotension (MAP <60 mmHg) was detected by the
      oscillometer with a sensitivity >=83% and specificity >=98% at all locations.
      CONCLUSIONS: This oscillometric device met the 2007 American College of
      Veterinary Internal Medicine guidelines for measurement of BP on the thoracic
      limb. There was good agreement between the oscillometer and invasive measurement
      of MAP at all locations. CLINICAL RELEVANCE: MAP is the driving pressure for
      tissue perfusion, thus MAP measurement is clinically essential. This
      oscillometric device yields reliable MAP measurements at three anatomical
      locations over a wide range of BP and can identify hypotension with high
      sensitivity and specificity.

PMID- 28514937
TI  - Removal of dibutyl phthalate from aqueous environments using a nanophotocatalytic
      Fe, Ag-ZnO/VIS-LED system: modeling and optimization.
AB  - An (Fe, Ag) co-doped ZnO nanostructure was synthesized by a simple chemical co
      precipitation method and used for the degradation of dibutyl phthalate (DBP) in
      aqueous solution under visible light-emitting diode (LED) irradiation. (Fe, Ag)
      co-doped ZnO nanorods were characterized by powder X-ray diffraction, Fourier
      transform infrared spectroscopy, UV-VIS diffuse reflectance spectroscopy,
      elemental mapping, Field emission scanning electron microscopy, transmission
      electron microscope and Brunauer-Emmett-Teller surface area analysis. A Central
      Composite Design was used to optimize the reaction parameters for the removal of
      DBP by the (Fe, Ag) co-doped ZnO nanorods. The four main reaction parameters
      optimized in this study were the following: pH, time of radiation, concentration
      of the nanorods and initial DBP concentration. The interaction between the four
      parameters was studied and modeled using the Design Expert 10 software. A maximum
      reduction of 95% of DBP was achieved at a pH of 3, a photocatalyst concentration
      of 150 mg L-1 and a DBP initial DBP concentration of 15 mg L-1. The results
      showed that the (Fe, Ag) co-doped ZnO nanorods under low power LED irradiation
      can be used as an effective photocatalyst for the removal of DBP from aqueous
      solutions.

PMID- 28514938
TI  - Characterization and Standardization of Cultured Cardiac Fibroblasts for Ex Vivo
      Models of Heart Fibrosis and Heart Ischemia.
AB  - A full understanding of cardiac fibroblast (cFB) biology is essential to study
      the adverse cardiac remodeling and recovery of myocardium infarction. However,
      compared to cardiac myocytes, cFBs are less well characterized. Important
      questions, including the variability introduced by cell age (neonatal vs. adult),
      culture conditions (passage, plate coating, and culture medium), and responses to
      stimuli (e.g., hypoxia and drug treatments), have not been well addressed and
      standardization of techniques is lacking. This variability invites inconsistency
      and the confounding of study conclusions. Thus, we here focus on characterizing
      cell responses and standardizing procedures for cFB isolation and culture
      conditions to provide reliable platforms to address important questions about cFB
      proliferation, activation, collagen matrix formation, and responses to relevant
      stimuli. Thirty litters of 1-3-day pups and 30 female (240-330 g) Sprague-Dawley
      rats were used to isolate neonatal and adult cFBs. We detail and validate
      procedures to isolate cFBs for the use of culture or direct analysis. We
      characterize the differences between neonatal and adult cFBs, define the changes
      of cFBs during serial passage, and identify the response of cFBs to different
      culture conditions. We have also established models for the functional screening
      of profibrotic and antifibrotic drugs based on cFB proliferation, myofibroblast
      activation, and pericellular collagen matrix formation, and models of
      hypoxia/reoxygenation with appropriate time course and media conditions to
      achieve consistent cell injury. Our standardized procedures will ensure
      consistency in assessing cFB function. This original contribution provides a
      valid platform for the ex vivo investigation of the role of cFBs in cardiac
      ischemia and fibrosis.

PMID- 28514939
TI  - Antioxidant properties of drugs used in Type 2 diabetes management: could they
      contribute to, confound or conceal effects of antioxidant therapy?
AB  - OBJECTIVES: This is a narrative review, investigating the antioxidant properties
      of drugs used in the management of diabetes, and discusses whether these
      antioxidant effects contribute to, confound, or conceal the effects of
      antioxidant therapy. METHODS: A systematic search for articles reporting trials,
      or observational studies on the antioxidant effect of drugs used in the treatment
      of diabetes in humans or animals was performed using Web of Science, PubMed, and
      Ovid. Data were extracted, including data on a number of subjects, type of
      treatment (and duration) received, and primary and secondary outcomes. The
      primary outcomes were reporting on changes in biomarkers of antioxidants
      concentrations and secondary outcomes were reporting on changes in biomarkers of
      oxidative stress. RESULTS: Diabetes Mellitus is a disease characterized by
      increased oxidative stress. It is often accompanied by a spectrum of other
      metabolic disturbances, including elevated plasma lipids, elevated uric acid,
      hypertension, endothelial dysfunction, and central obesity. This review shows
      evidence that some of the drugs in diabetes management have both in vivo and in
      vitro antioxidant properties through mechanisms such as scavenging free radicals
      and upregulating antioxidant gene expression. CONCLUSION: Pharmaceutical agents
      used in the treatment of type 2 diabetes has been shown to exert an antioxidant
      effect..

PMID- 28514940
TI  - The effect of initial teaching on evaluation of left ventricular volumes by
      cardiovascular magnetic resonance imaging: comparison between complete and
      intermediate beginners and experienced observers.
AB  - BACKGROUND: High reproducibility and low intra- and interobserver variability are
      important strengths of cardiac magnetic resonance (CMR). In clinical practice a
      significant learning curve may however be observed. Basic CMR courses offer an
      average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV)
      function analysis. The purpose of this study was to evaluate the effect of
      initial teaching on complete and intermediate beginners' quantitative
      measurements of LV volumes and function by CMR. METHODS: Standard clinical cine
      CMR sequences were acquired in 15 patients. Five observers (two complete
      beginners, one intermediate, two experienced) measured LV volumes. Before initial
      evaluation beginners read the SCMR guidelines on CMR analysis. After initial
      evaluation, beginners participated in a two-hour teaching session including cases
      and hands-on training, representative for most basic CMR courses, after which it
      is uncertain to what extent different centres provide continued teaching and
      feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations.
      Agreement, accuracy, precision, repeatability and reliability were assessed by
      Bland-Altman, coefficient of variation, and intraclass correlation coefficient
      methods. RESULTS: Endocardial DSC improved after teaching (+0.14 +/- 0.17;p <
      0.001) for complete beginners. Low intraobserver variability was found before and
      after teaching, however with wide limits of agreement. Beginners underestimated
      volumes by up to 44 ml (EDV), 27 ml (ESV) and overestimated LVM by up to 53 g
      before teaching, improving to an underestimation of up to 9 ml (EDV), 7 ml (ESV)
      and an overestimation of up to 30 g (LVM) after teaching. For the intermediate
      beginner, however, accuracy was quite high already before teaching. CONCLUSIONS:
      Initial teaching to complete beginners increases accuracy for assessment of LV
      volumes, however with high bias and low precision even after standardised
      teaching as offered in most basic CMR courses. Even though the intermediate
      beginner showed quite high accuracy already before teaching, precision did
      generally not improve after standardised teaching. To maintain CMR as a technique
      known for high accuracy and reproducibility and low intra- and inter-observer
      variability for quantitative measurements, internationally standardised training
      should be encouraged including high-quality feedback mechanisms. Objective
      measurements of training methods, training duration and, above all, quality of
      assessments are required.

PMID- 28514941
TI  - Effects of marker density and population structure on the genomic prediction
      accuracy for growth trait in Pacific white shrimp Litopenaeus vannamei.
AB  - BACKGROUND: Due to the great advantages in selection accuracy and efficiency,
      genomic selection (GS) has been widely studied in livestock, crop and aquatic
      animals. Our previous study based on one full-sib family of Litopenaeus vannamei
      (L. vannamei) showed that GS was feasible in penaeid shrimp. However, the
      applicability of GS might be influenced by many factors including heritability,
      marker density and population structure etc. Therefore it is necessary to
      evaluate the major factors affecting the prediction ability of GS in shrimp. The
      aim of this study was to evaluate the factors influencing the GS accuracy for
      growth traits in L. vannamei. Genotype and phenotype data of 200 individuals from
      13 full-sib families were used for this analysis. RESULTS: In the present study,
      the heritability of growth traits in L. vannamei was estimated firstly based on
      the full set of markers (23 K). It was 0.321 for body weight and 0.452 for body
      length. The estimated heritability increased rapidly with the increase of the
      marker density from 0.05 K to 3.2 K, and then it tended to be stable for both
      traits. For genomic prediction on the growth traits in L. vannamei, three
      statistic models (RR-BLUP, BayesA and Bayesian LASSO) showed similar performance
      for the prediction accuracy of genomic estimated breeding value (GEBV). The
      prediction accuracy was improved with the increasing of marker density. However,
      the marker density would bring a weak effect on the prediction accuracy after the
      marker number reached 3.2 K. In addition, the genetic relationship between
      reference and validation population could influence the GS accuracy
      significantly. A distant genetic relationship between reference and validation
      population resulted in a poor performance of genomic prediction for growth traits
      in L. vannamei. CONCLUSIONS: For the growth traits with moderate or high
      heritability, such as body weight and body length, the number of about 3.2 K SNPs
      distributed evenly along the genome was able to satisfy the need for accurate GS
      prediction in the investigated L.vannamei population. The genetic relationship
      between the reference population and the validation population showed significant
      effects on the accuracy for genomic prediction. Therefore it is very important to
      optimize the design of the reference population when applying GS to shrimp
      breeding.

PMID- 28514942
TI  - Corneal biomechanical properties in healthy children measured by corneal
      visualization scheimpflug technology.
AB  - BACKGROUND: The aim of this study was to evaluate corneal biomechanical
      properties in a population of healthy children in China using corneal
      visualization Scheimpflug technology (CST). METHODS: All children underwent
      complete bi-ocular examinations. CST provided intraocular pressure (IOP) and
      corneal biomechanical parameters, including time, velocity, length and
      deformation amplitude at first applanation (A1T, A1V, A1L, A1DA), at second
      applanation (A2T, A2V, A2L, A2DA), highest concavity time (HCT), maximum
      deformation amplitude (MDA), peak distance (PD), and radius of curvature (RoC).
      Pearson correlation analysis was used to assess the impacts of demographic
      factors, central corneal thickness (CCT), spherical equivalent (SE), and IOP on
      corneal biomechanics. RESULTS: One hundred eight subjects (32 girls and 76 boys)
      with the mean age of 10.80 +/- 4.13 years (range 4 to18 years) were included in
      the final analyses. The right and left eyes were highly symmetrical in SE (p =
      0.082), IOP (p = 0.235), or CCT (p = 0.210). Mean A1T of the right eyes was 7.424
      +/- 0.340 ms; the left eyes 7.451 +/- 0.365 ms. MDA was 0.993 +/- 0.102 mm in the
      right eyes and 0.982 +/- 0.100 mm in the left eyes. Mean HCT of the right eyes
      was 16.675 +/- 0.502 ms; the left eyes 16.735 +/- 0.555 ms. All CST parameters of
      both eye were remarkably symmetrical with the exception of A2L (p = 0.006), A1DA
      (p = 0.025). The majority of CST parameters of both eyes were significantly
      correlated with CCT and IOP (p < 0.05). However, age, SE, and sex exert little
      influence on the CST measurements. CONCLUSIONS: This study found interocular
      symmetry in corneal biomechanics in healthy children eyes. Several CST
      biomechanical parameters in children are modified by CCT and IOP.

PMID- 28514943
TI  - Sex differences underlying orofacial varicella zoster associated pain in rats.
AB  - BACKGROUND: Most people are initially infected with varicella zoster virus (VZV)
      at a young age and this infection results in chickenpox. VZV then becomes latent
      and reactivates later in life resulting in herpes zoster (HZ) or "shingles".
      Often VZV infects neurons of the trigeminal ganglia to cause ocular problems,
      orofacial disease and occasionally a chronic pain condition termed post-herpetic
      neuralgia (PHN). To date, no model has been developed to study orofacial pain
      related to varicella zoster. Importantly, the incidence of zoster associated pain
      and PHN is known to be higher in women, although reasons for this sex difference
      remain unclear. Prior to this work, no animal model was available to study these
      sex-differences. Our goal was to develop an orofacial animal model for zoster
      associated pain which could be utilized to study the mechanisms contributing to
      this sex difference. METHODS: To develop this model VZV was injected into the
      whisker pad of rats resulting in IE62 protein expression in the trigeminal
      ganglia; IE62 is an immediate early gene in the VZV replication program. RESULTS:
      Similar to PHN patients, rats showed retraction of neurites after VZV infection.
      Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated
      the pain response after whisker pad injection. Aversive behavior was
      significantly greater for up to 7 weeks in VZV injected rats over control
      inoculated rats. Sex differences were also seen such that ovariectomized and
      intact female rats given the lower dose of VZV showed a longer affective response
      than male rats. The phase of the estrous cycle also affected the aversive
      response suggesting a role for sex steroids in modulating VZV pain. CONCLUSIONS:
      These results suggest that this rat model can be utilized to study the mechanisms
      of 1) orofacial zoster associated pain and 2) the sex differences underlying
      zoster associated pain.

PMID- 28514944
TI  - Short term visual outcomes of a new trifocal intraocular lens.
AB  - BACKGROUND: Today, patients often expect to achieve spectacle independance after
      cataract surgery. New trifocal intraocular lenses have been developed to try and
      fullfill this demand. The purpose of this study is to report the short-term
      visual outcomes of a new trifocal intraocular lens (AcrySof PanOptixTM). METHODS:
      Consecutive adult patients undergoing cataract surgery with bilateral
      implantation of the study intraocular lens in a private practice clinic were
      considered for inclusion. Exclusion criteria were the presence of other ocular
      pathologies or preoperative astigmatism >1.5 diopters (D). Patients with
      intraoperative complications were excluded from analysis. One month after surgery
      patients underwent: monocular defocus curve; monocular and binocular uncorrected
      visual acuity in photopic and mesopic conditions, for far (4 m), intermediate (60
      cm) and near (33 cm) distances and binocular contrast sensitivity. Patients
      completed a visual satisfaction questionnaire between 9 and 12 months after
      surgery. RESULTS: One hundred and sixteen eyes of fifty-eight patients receiving
      bilateral implantation of the study intraocular lens were analysed. Mean
      binocular uncorrected visual acuity in photopic conditions was 0.03 LogMAR for
      far, 0.12 for intermediate and 0.02 for near distances. All patients achieved a
      binocular uncorrected visual acuity better than 0.3 LogMAR (20/40 Snellen
      equivalent) for distance and near vision and 94.8% of patients for intermediate
      vision. Mesopic binocular uncorrected visual acuity values were similar to
      photopic values. The monocular defocus curves showed that the best visual acuity
      was reached at a vergence of 0.00D. Visual acuity dropped slightly at -1.00D and
      peaked again at -2.00D. Visual acuities better than 0.2 LogMAR were maintained
      between -2.50D and +0.50D. Contrast sensitivity was high and similar in photopic
      and mesopic conditions. As regards patient-evaluated outcomes, only 2 patients
      (3.4%) were fairly dissatisfied with their sight after surgery. Three patients
      (5.1%) reported the need for spectacle correction for certain activities. All
      other patients (94.8%) reported never using spectacle correction. CONCLUSIONS:
      The PanOptix trifocal IOL provides good short-term visual outcomes, with good
      intermediate performance and excellent patient-reported satisfaction. The similar
      values achieved in mesopic and photopic conditions in binocular uncorrected
      visual acuity and contrast sensitivity suggest low pupillary dependence for light
      distribution. TRIAL REGISTRATION NUMBER: ISRCTN60143265 , retrospectively
      registered on the 24th of April 2017.

PMID- 28514945
TI  - TUmor-volume to breast-volume RAtio for improving COSmetic results in breast
      cancer patients (TURACOS); a randomized controlled trial.
AB  - BACKGROUND: Cosmetic result following breast conserving surgery (BCS) for cancer
      influences quality of life and psychosocial functioning in breast cancer
      patients. A preoperative prediction of expected cosmetic result following BCS is
      not (yet) standard clinical practice and therefore the choice for either
      mastectomy or BCS is still subjective. Recently, we showed that tumour volume to
      breast volume ratio as well as tumour location in the breast are independent
      predictors of superior cosmetic result following BCS. Implementation of a
      prediction model including both factors, has not been studied in a prospective
      manner. This study aims to improve cosmetic outcome by implementation of a
      prediction model in the treatment decision making for breast cancer patients
      opting for BCS. METHODS/DESIGN: Multicentre, single-blinded, randomized
      controlled trial comparing standard preoperative work-up to a preoperative work
      up with addition of the prediction model. Tumour volume to breast volume ratio
      and tumour location in the breast will be used to predict cosmetic outcome in
      invasive breast cancer patients opting for BCS. Three dimensional (3D)
      ultrasonography will be used to measure the tumour volume to breast volume ratio
      needed for the prediction model. Sample size was estimated based on a 14%
      improvement in incidence of superior cosmetic result one year after BCS (71% in
      the control group versus 85% in the intervention group). Primarily cosmetic
      outcome will be evaluated by a 6-member independent panel. Secondary endpoints
      include; (1) patient reported outcome measured by BREAST-Q, EORTC-QLQ-C30/BR23
      and EQ-5D-5 L (2) cosmetic outcome as assessed through the BCCT.core software,
      (3) radiation-induced reaction (4) surgical treatment performed, (5) pathological
      result and (6) cost-effectiveness. Follow-up data will be collected for 3 years
      after surgery or finishing radiotherapy. DISCUSSION: This randomized controlled
      trial examines the value of a preoperative prediction model for the treatment
      decision making. It aims for a superior cosmetic result in breast cancer patients
      opting for BCS. We expect improvement of patients' quality of life and
      psychosocial functioning in a cost-effective way. TRIAL REGISTRATION:
      Prospectively registered, February 17th 2015, at 'Nederlands Trialregister -
      NTR4997 '.

PMID- 28514946
TI  - Open Questions: We don't really know anything, do we? Open questions in sensory
      biology.
AB  - Senses connect organisms to both the world and to each other, yet there is much
      we don't know about them. Using examples drawn primarily from the author's
      subfield of vision research, this article discusses five major open questions.

PMID- 28514947
TI  - Enhanced chlorhexidine skin penetration with 1,8-cineole.
AB  - BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this
      study was to compare the depth of CHG skin permeation from solutions containing
      either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70%
      (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz
      diffusion cells was carried out. Full thickness human skin was mounted onto the
      cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the
      skin surface. After twenty-four hours the skin was sectioned horizontally in 100
      MUm slices to a depth of 2000 MUm and the concentration of CHG in each section
      quantified using high performance liquid chromatography (HPLC). The data were
      analysed with repeated measures analysis of variance. RESULTS: The concentration
      of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% -
      74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin
      compared to a CHG solution which did not contain this terpene (P = 0.042).
      CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8
      cineole, which is the major component of eucalyptus oil. This may reduce the
      numbers of microorganisms located in the deeper layers of the skin which
      potentially could decrease the risk of surgical site infection.

PMID- 28514948
TI  - Demystification of animal symmetry: symmetry is a response to mechanical forces.
AB  - : ?: Symmetry is an eye-catching feature of animal body plans, yet its causes are
      not well enough understood. The evolution of animal form is mainly due to changes
      in gene regulatory networks (GRNs). Based on theoretical considerations regarding
      fundamental GRN properties, it has recently been proposed that the animal genome,
      on large time scales, should be regarded as a system which can construct both the
      main symmetries - radial and bilateral - simultaneously; and that the expression
      of any of these depends on functional constraints. Current theories explain
      biological symmetry as a pattern mostly determined by phylogenetic constraints,
      and more by chance than by necessity. In contrast to this conception, I suggest
      that physical effects, which in many cases act as proximate, direct, tissue
      shaping factors during ontogenesis, are also the ultimate causes - i.e. the
      indirect factors which provide a selective advantage - of animal symmetry, from
      organs to body plan level patterns. In this respect, animal symmetry is a
      necessary product of evolution. This proposition offers a parsimonious view of
      symmetry as a basic feature of the animal body plan, suggesting that molecules
      and physical forces act in a beautiful harmony to create symmetrical structures,
      but that the concert itself is directed by the latter. REVIEWERS: This article
      was reviewed by Eugene Koonin, Zoltan Varga and Michael Manuel.

PMID- 28514949
TI  - Membrane of Candida albicans as a target of berberine.
AB  - BACKGROUND: We investigated the mechanisms of anti-Candida action of isoquinoline
      alkaloid berberine, active constituent of medically important plants of Barberry
      species. METHODS: The effects on membrane, morphological transition, synthesis of
      ergosterol and the consequent changes in membrane permeability have been studied.
      Polarization and lipid peroxidation level of the membrane following berberine
      treatment have been addressed. RESULTS: Minimal inhibitory concentration (MIC) of
      berberine against C. albicans was 17.75 MUg/mL. Cytotoxic effect of berberine was
      concentration dependent, and in sub-MIC concentrations inhibit morphological
      transition of C. albicans cells to its filamentous form. Results showed that
      berberine affects synthesis of membrane ergosterol dose-dependently and induces
      increased membrane permeability causing loss of intracellular material to the
      outer space (DNA/protein leakage). Berberine also caused membrane depolarization
      and lipid peroxidation of membrane constituents indicating its direct effect on
      the membrane. Moreover, ROS levels were also increased following berberine
      treatment indicating further the possibility of membrane damage. CONCLUSION:
      Based on the obtained results it seems that berberine achieves its anti-Candida
      activity by affecting the cell membrane.

PMID- 28514951
TI  - A computerized red glass test for quantifying diplopia.
AB  - BACKGROUND: Accurate evaluation of diplopia during bedside physical examination
      is challenging. We developed a new computerized red glass test (CRT) to detect,
      localize, and quantify diplopia and investigated whether the CRT is useful and
      feasible. METHODS: During the CRT, a white dot randomly appears on a monitor.
      Because a red glass is applied on the right eye, a patient can see one white dot
      and one red dot when diplopia is present. We defined the degree of diplopia as
      the direct distance of the two points with the largest deviation and compared the
      degree with the Hess score and Hess area ratio. RESULTS: We prospectively
      enrolled 14 patients with binocular diplopia. Test-retest reliability of the CRT
      was excellent (overall intraclass correlation coefficient = 0.948, 95% CI 0.939
      0.956). The degree of diplopia in the CRT was well correlated with both the Hess
      score (r = 0.719, p = 0.005) and the Hess area ratio (r = -0.620, p = 0.018).
      CONCLUSIONS: The CRT can easily detect the presence of diplopia and provided the
      quantitative values of the degree of diplopia. The CRT was useful and feasible
      for improving routine bedside examination.

PMID- 28514950
TI  - Lung function imaging methods in Cystic Fibrosis pulmonary disease.
AB  - Monitoring of pulmonary physiology is fundamental to the clinical management of
      patients with Cystic Fibrosis. The current standard clinical practise uses
      spirometry to assess lung function which delivers a clinically relevant
      functional readout of total lung function, however does not supply any visible or
      localised information. High Resolution Computed Tomography (HRCT) is a well
      established current 'gold standard' method for monitoring lung anatomical changes
      in Cystic Fibrosis patients. HRCT provides excellent morphological information,
      however, the X-ray radiation dose can become significant if multiple scans are
      required to monitor chronic diseases such as cystic fibrosis. X-ray phase
      contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis
      lung assessment which provides dynamic morphological and functional information,
      albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI)
      is a non-ionising radiation imaging method that is garnering growing interest
      among researchers and clinicians working with Cystic Fibrosis patients. Recent
      advances in MRI have opened up the possibilities to observe lung function in real
      time to potentially allow sensitive and accurate assessment of disease
      progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be
      tailored to clinical needs. While MRI offers significant promise it still suffers
      from poor spatial resolution and the development of an objective scoring system
      especially for ventilation assessment.

PMID- 28514952
TI  - Distributions and determinants of urinary biomarkers of organophosphate pesticide
      exposure in a prospective Spanish birth cohort study.
AB  - BACKGROUND: Prenatal exposure to organophosphate pesticides (OPs) has been
      associated with impaired child development. Pesticide exposure determinants need
      to be studied in order to identify sources and pathways of pesticide exposure.
      The aim of this paper is to describe prenatal exposure to OPs and evaluate the
      associated factors in pregnant women. METHODS: The study population consisted of
      pregnant women (n = 573) who participated in the INMA birth cohort study in
      Valencia (Spain, 2003-2006). OP metabolites were analyzed in maternal urine at
      the 32nd week of gestation using a liquid chromatography-high resolution mass
      spectrometry method. The analysis included non-specific (diethyl phosphate [DEP],
      diethyl thiophosphate [DETP], dimethyl thiophosphate [DMTP], dimethyl
      dithiophosphate [DMDTP]) and specific metabolites (2-diethylamino-6-methyl-4
      pyrimidinol [DEAMPY], 2-isopropyl-4-methyl-6-hydroxypyrimidine [IMPY], para
      nitrophenol [PNP], and 3,5,6-trichloro-2-pyridinol [TCPY]). Information about the
      sociodemographic, environmental, and dietary characteristics was obtained by
      questionnaire. The association between log-transformed OPs and covariates was
      analyzed using multivariable interval censored regression. RESULTS: The detection
      frequencies were low, DMTP and TCPY being the most frequently detected
      metabolites (53.8% and 39.1%, respectively). All the OP metabolites were
      positively associated with maternal intake of fruits and vegetables. Other
      maternal characteristics related to the OPs were body mass index (BMI) before
      pregnancy and smoking habit during pregnancy. Women with lower BMI and those who
      did not smoke presented higher OP concentrations. Moreover, mothers who had a
      yard or garden with plants at home or who lived in an urban area were also more
      exposed to OPs. CONCLUSIONS: The OP detection frequencies and the concentrations
      observed in our study population were low, compared with most of the previously
      published studies. Given the high vulnerability of the fetus to neurotoxicant
      exposure, further research on the determinants of the body burden of OPs during
      pregnancy would be necessary. The knowledge gained from such studies would
      enhance the effectiveness of public health control and future recommendations in
      order to reduce the risk to both the health of pregnant women and the health and
      development of their children.

PMID- 28514953
TI  - Emergence of Babesia canis in southern England.
AB  - BACKGROUND: The United Kingdom is considered free of autochthonous transmission
      of canine babesiosis although cases are reported in dogs associated with recent
      travel abroad. During the winter months of 2015/16, a cluster of cases of disease
      in dogs with signs suggestive of canine babesiosis were reported in Harlow,
      Essex. METHODS: Babesia species were detected in dog blood samples by Giemsa
      staining of blood smears and by pan-piroplasm PCRs. Babesia species were also
      detected in extracts of tick DNA using pan-piroplasm PCRs. DNA sequencing and
      phylogenetic analysis was used to confirm the species of Babesia present in dog
      blood and tick samples. Tick species were identified by PCR-sequencing based on
      amplification of the cytochrome c oxidase subunit one (cox1) gene. Dermacentor
      reticulatus ticks were sampled from field sites in England and Wales. RESULTS:
      Blood smear analysis on samples taken from some of the affected dogs confirmed
      the presence of a large Babesia species within erythrocytes. A tick recovered
      from one of these cases was identified as Dermacentor reticulatus, a species with
      a limited distribution in England and Wales, but a known vector of canine
      babesiosis in continental Europe. Babesia canis was subsequently identified in
      blood samples obtained from three clinical cases (all dogs) within the area and
      from ticks associated with these dogs. A field survey detected 17 adult D.
      reticulatus ticks from one area visited by the affected dogs. Fourteen of these
      ticks were shown to be positive for the B. canis parasite, implicating them as a
      potential source for babesiosis in Harlow. In order to assess whether the
      parasite is present in more than one tick population, D. reticulatus ticks from
      across England and Wales were screened for the presence of Babesia species. In
      addition to the Harlow site, a further five locations where D. reticulatus is
      present were screened for Babesia species. Babesia was not detected from most
      sites tested but one tick from a single location in Wales was positive for B.
      canis. CONCLUSIONS: Infection with B. canis was confirmed in a number of dogs in
      Harlow, Essex, with no history of travel outside of the country. The same
      pathogen was identified in field-caught D. reticulatus ticks in the same area and
      is considered the likely source of infection. This highlights the need for
      vigilance by veterinary surgeons for future outbreaks of tick-borne disease in
      dogs.

PMID- 28514955
TI  - Label-free biosensing of Salmonella enterica serovars at single-cell level.
AB  - BACKGROUND: The emerging nanotechnologies have greatly facilitated the
      development of label-free biosensors. The atomic force microscopy (AFM) has been
      used to study the molecular mechanism of the reactions for protein and aptamers.
      The surface plasmon resonance (SPR) have been used in fast detections of various
      pathogens such as bacteria. This study used both AFM and SPR to investigate the
      complex reactions between aptamers and outer membrane proteins (OMPs) on the
      surface of S. typhimurium. RESULTS: Two DNA aptamers were used for the label-free
      detections of S. typhimurium by AFM and SPR. The aptamers have specific binding
      affinities to the OMPs of S. typhimurium. At single-molecule level, the high
      resolution AFM topography and recognition images distinguished the OMPs on the
      bacteria surface, which is the first time the location of individual outer
      membrane protein have been determined on Salmonella surface. E. coli in the
      control experiments didn't generate recognition signals, which proved the
      specificity of these two aptamers to S. typhimurium. The off-rate values for the
      interactions of these two aptamers to the OMPs were estimated as 5.2 * 10-3 and
      7.4 * 10-3 s-1, respectively, by the AFM dynamic force microscopy (DFS). The
      force and extension values form DFS measurements were used to distinguish the two
      aptamers. The surface membrane model was proposed to explain the complex
      correlations among force and extension values. Next, these two aptamers were used
      in the bulk solution detections of S. typhimurium. The gold chips in SPR
      experiments were modified with carboxymethylated-dextran (CD), followed by
      aptamers immobilization, to reduce the non-specific binding signals. The limit of
      detection (LOD) was determined as 3 * 104 CFU mL-1. CONCLUSIONS: The AFM single
      molecule study revealed detailed information about the unbinding force and
      extension of the aptamer in complex biological reactions. The careful analysis of
      the experimental results provide better understanding of the molecular mechanism
      of OMPs reactions. The single-molecule measurements are helpful in evaluating the
      specificity of binding reagents, such as aptamers, in bulk solution detections.
      The protocols used in the SPR detections can be expanded into the label-free
      detections of other bacterial pathogens.

PMID- 28514954
TI  - Needle exchange programs for the prevention of hepatitis C virus infection in
      people who inject drugs: a systematic review with meta-analysis.
AB  - BACKGROUND: Previous research on the effectiveness of needle exchange programs
      (NEP) in preventing hepatitis C virus (HCV) in people who inject drugs (PWID) has
      shown mixed findings. The purpose of this study was to use the meta-analytic
      approach to examine the association between NEP use and HCV prevention in PWIDs.
      METHODS: Study inclusion criteria were (1) observational studies, (2) PWIDs, (3)
      NEP use, (4) HCV status ascertained by serological testing, (5) studies published
      in any language since January 1, 1989, and (6) data available for measures of
      association. Studies were located by searching four electronic databases and
      cross-referencing. Study quality was assessed using the Newcastle Ottawa (NOS)
      scale. A ratio measure of association was calculated for each result from cohort
      or case-control studies and pooled using a random effects model. Odds ratio (OR)
      and hazard ratio (HR) models were analyzed separately. Results were considered
      statistically significant if the 95% confidence interval (CI) did not cross 1.
      Heterogeneity was estimated using Q and I 2 with alpha values for Q <= 0.10
      considered statistically significant. RESULTS: Of the 555 citations reviewed, 6
      studies containing 2437 participants were included. Studies had an average NOS
      score of 7 out of 9 (77.8%) stars. Concerns over participant representativeness,
      unclear adjustments for confounders, and bias from participant nonresponse and
      loss to follow-up were noted. Results were mixed with the odds ratio model
      indicating no consistent association (OR, 0.51, 95% CI, 0.05-5.15), and the
      hazard ratio model indicating a harmful effect (HR, 2.05, 95% CI, 1.39-3.03).
      Substantial heterogeneity (p <= 0.10) and moderate to large inconsistency (I 2 
      >= 66%) were observed for both models. CONCLUSIONS: The impact of NEPs on HCV
      prevention in PWIDs remains unclear. There is a need for well-designed research
      studies employing standardized criteria and measurements to clarify this issue.
      TRIAL REGISTRATION: PROSPERO CRD42016035315.

PMID- 28514956
TI  - Transcriptome analysis for the identification of cellular markers related to
      trabecular meshwork differentiation.
AB  - BACKGROUND: Development of primary open-angle glaucoma (POAG) is associated with
      the malfunctioning trabecular meshwork (TM). Cell therapy offers great potential
      for the treatment of POAG, but requires the generation of functional TM cells in
      vitro to replace the lost/dysfunctional cells. TM differentiation in vitro from
      various stem cell types must be monitored by the expression of specific markers.
      However, no single definitive marker of the TM has been identified. RESULTS: To
      identify robust markers of TM differentiation, we performed global transcriptome
      profiling using high-density oligonucleotide microarray on ex vivo TM tissue and
      cultured TM progenitors. Corneal and scleral tissues were also used in the
      analysis. After removal of genes expressed in the cornea and sclera, 18 genes
      were identified that were differentially expressed in the TM relative to the
      other samples. CDH23, F5, KCNAB1, FGF9, SPP1, and HEY1 were selected among the
      genes highly expressed in the TM, together with BDNF which was repressed,
      compared to progenitors for further investigation. Expression analysis by qPCR
      verified the differential expression and immunofluorescence of the anterior
      segment confirmed strong expression in the TM. CONCLUSIONS: Three independent
      cohort of expression studies have identified novel markers, fitting in
      identifying TM cells and in evaluating directed TM differentiation in vitro.

PMID- 28514957
TI  - High lymphatic vessel density and presence of lymphovascular invasion both
      predict poor prognosis in breast cancer.
AB  - BACKGROUND: Lymphatic vessel density and lymphovascular invasion are commonly
      assessed to identify the clinicopathological outcomes in breast cancer. However,
      the prognostic values of them on patients' survival are still uncertain. METHODS:
      Databases of PubMed, Embase, and Web of Science were searched from inception up
      to 30 June 2016. The hazard ratio with its 95% confidence interval was used to
      determine the prognostic effects of lymphatic vessel density and lymphovascular
      invasion on disease-free survival and overall survival in breast cancer. RESULTS:
      Nineteen studies, involving 4215 participants, were included in this study. With
      the combination of the results of lymphatic vessel density, the pooled hazard
      ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free
      survival and 2.88 (2.07-4.01) for overall survival, respectively. For
      lymphovascular invasion study, the pooled hazard ratios and 95% confidence
      intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87)
      for overall survival, respectively. In addition, 29.56% (827/2798) of
      participants presented with lymphovascular invasion in total. CONCLUSIONS: Our
      study demonstrates that lymphatic vessel density and lymphovascular invasion can
      predict poor prognosis in breast cancer. Standardized assessments of lymphatic
      vessel density and lymphovascular invasion are needed.

PMID- 28514958
TI  - Neonatal respiratory morbidity following exposure to chorioamnionitis.
AB  - BACKGROUND: There are conflicting results in the literature on the impact of
      chorioamnionitis on neonatal respiratory morbidities. However, most studies are
      based on small clinical samples and fail to account for the competing risk of
      perinatal death. This study aimed to determine whether chorioamnionitis affects
      the incidence of respiratory distress syndrome (RDS) and bronchopulmonary
      dysplasia (BPD) after accounting for the increased risk of death. METHODS:
      Retrospective cohort study using linked birth and infant death registration and
      hospitalization records from Washington State between 2002 and 2011 (n = 763,671
      singleton infants and n = 56,537 singleton preterm infants). Logistic regression
      models based on the traditional and fetuses-at-risk approaches were used to model
      two composite outcomes namely RDS and perinatal death and BPD and perinatal
      death. Confounders adjusted for in the models included maternal age, race,
      diabetes, hypertension, antenatal corticosteroids, mode of delivery and infant
      sex. RESULTS: While models using the traditional approach found a significant
      association only between chorioamnionitis and composite BPD and perinatal death
      (OR = 1.23, 95% CI: 1.01-1.50); using the fetuses-at-risk approach, there was a
      significant association between chorioamnionitis and both composite outcomes (RDS
      and perinatal death OR = 2.74, 2.50-3.01; BPD and perinatal death OR = 5.18, 95%
      CI: 4.39-6.11). CONCLUSION: The fetuses-at-risk approach models the causal impact
      of chorioamnionitis on the development of the fetal lung and shows an increased
      risk of RDS, BPD and perinatal death associated with such maternal infection.

PMID- 28514960
TI  - Segmental testicular infarction: a case report.
AB  - BACKGROUND: Segmental testicular infarction is a very rare condition, which can
      mimic a testicular torsion or testicular cancer. Correct diagnosis is difficult
      but it is important to avoid unnecessary radical treatment. CASE PRESENTATION: We
      report a clinical case of a 36-year-old white man who presented at our emergency
      department with subacute testicular pain. A urine analysis, Doppler ultrasound,
      surgical exploration, blood analysis, and magnetic resonance imaging were
      performed to diagnose his condition, to exclude a testicular torsion, and to
      raise confidence in its non-malignancy. He was treated conservatively. At follow
      up, a few months after the incident, he no longer had complaints. Ultrasonography
      showed remaining hypo-echogenicity of the left upper pole, indicating a sequel of
      ischemia. CONCLUSIONS: Segmental testicular infarction is a rare condition which
      can be easily confused with a testicular torsion or a testicular tumor. This case
      report can be helpful in recognizing and diagnosing this condition. Making the
      right diagnosis is important since it can prevent an unnecessary radical
      treatment.

PMID- 28514959
TI  - Prevention of postpartum haemorrhage by community-based auxiliary midwives in
      hard-to-reach areas of Myanmar: a qualitative inquiry into acceptability and
      feasibility of task shifting.
AB  - BACKGROUND: In Myanmar, postpartum haemorrhage is the leading cause of maternal
      mortality and contributes to around 30% of all maternal deaths. The World Health
      Organization recommends training and supporting auxiliary midwives to administer
      oral misoprostol for prevention of postpartum haemorrhage in resource-limited
      settings. However, use of misoprostol by auxiliary midwives has not formally been
      approved in Myanmar. Our study aimed to explore community and provider
      perspectives on the roles of auxiliary midwives and community-level provision of
      oral misoprostol by auxiliary midwives. METHODS: A qualitative inquiry was
      conducted in Ngape Township, Myanmar. A total of 15 focus group discussions with
      midwives, auxiliary midwives, community members and mothers with children under
      the age of three were conducted. Ten key informant interviews were performed with
      national, district and township level health planners and implementers of
      maternal and child health services. All audio recordings were transcribed
      verbatim in Myanmar language. Transcripts of focus group discussions were fully
      translated into English before coding, while key informants' data were coded in
      Myanmar language. Thematic analysis was done using ATLAS.ti software. RESULTS:
      Home births are common and auxiliary midwives were perceived as an essential care
      provider during childbirth in hard-to-reach areas. Main reasons provided were
      that auxiliary midwives are more accessible than midwives, live in the hard-to
      reach areas, and are integrated in the community and well connected with
      midwives. Auxiliary midwives generally reported that their training involved
      instruction on active management of the third stage of labour, including use of
      misoprostol, but not all auxiliary midwives reported using misoprostol in
      practice. Supportive reasons for task-shifting administration of oral misoprostol
      to auxiliary midwives included discussions around the good relationship and trust
      between auxiliary midwives and midwives, whereby midwives felt confident
      distributing misoprostol to auxiliary midwives. However, the lack of clear
      government-level written permission to distribute the drug was perceived as a
      barrier to task shifting. CONCLUSION: This study highlights the acceptability of
      misoprostol use by auxiliary midwives to prevent postpartum haemorrhage, and
      findings suggest that it should be considered as a promising intervention for
      task shifting in Myanmar.

PMID- 28514961
TI  - How many people will need palliative care in 2040? Past trends, future
      projections and implications for services.
AB  - BACKGROUND: Current estimates suggest that approximately 75% of people
      approaching the end-of-life may benefit from palliative care. The growing numbers
      of older people and increasing prevalence of chronic illness in many countries
      mean that more people may benefit from palliative care in the future, but this
      has not been quantified. The present study aims to estimate future population
      palliative care need in two high-income countries. METHODS: We used mortality
      statistics for England and Wales from 2006 to 2014. Building on previous
      diagnosis-based approaches, we calculated age- and sex-specific proportions of
      deaths from defined chronic progressive illnesses to estimate the prevalence of
      palliative care need in the population. We calculated annual change over the 9
      year period. Using explicit assumptions about change in disease prevalence over
      time, and official mortality forecasts, we modelled palliative care need up to
      2040. We also undertook separate projections for dementia, cancer and organ
      failure. RESULTS: By 2040, annual deaths in England and Wales are projected to
      rise by 25.4% (from 501,424 in 2014 to 628,659). If age- and sex-specific
      proportions with palliative care needs remain the same as in 2014, the number of
      people requiring palliative care will grow by 25.0% (from 375,398 to 469,305
      people/year). However, if the upward trend observed from 2006 to 2014 continues,
      the increase will be of 42.4% (161,842 more people/year, total 537,240). In
      addition, disease-specific projections show that dementia (increase from 59,199
      to 219,409 deaths/year by 2040) and cancer (increase from 143,638 to 208,636
      deaths by 2040) will be the main drivers of increased need. CONCLUSIONS: If
      recent mortality trends continue, 160,000 more people in England and Wales will
      need palliative care by 2040. Healthcare systems must now start to adapt to the
      age-related growth in deaths from chronic illness, by focusing on integration and
      boosting of palliative care across health and social care disciplines. Countries
      with similar demographic and disease changes will likely experience comparable
      rises in need.

PMID- 28514962
TI  - Revisiting annual screening for latent tuberculosis infection in healthcare
      workers: a cost-effectiveness analysis.
AB  - BACKGROUND: In North America, tuberculosis incidence is now very low and risk to
      healthcare workers has fallen. Indeed, recent cohort data question routine annual
      tuberculosis screening in this context. We compared the cost-effectiveness of
      three potential strategies for ongoing screening of North American healthcare
      workers at risk of exposure. The analysis did not evaluate the cost-effectiveness
      of screening at hiring, and considered only workers with negative baseline tests.
      METHODS: A decision analysis model simulated a hypothetical cohort of 1000
      workers following negative baseline tests, considering duties, tuberculosis
      exposure, testing and treatment. Two tests were modelled, the tuberculin skin
      test (TST) and QuantiFERON(r)-TB-Gold In-Tube (QFT). Three screening strategies
      were compared: (1) annual screening, where workers were tested yearly; (2)
      targeted screening, where workers with high-risk duties (e.g. respiratory
      therapy) were tested yearly and other workers only after recognised exposure; and
      (3) post exposure-only screening, where all workers were tested only after
      recognised exposure. Workers with high-risk duties had 1% annual risk of
      infection, while workers with standard patient care duties had 0.3%. In an
      alternate higher-risk scenario, the corresponding annual risks of infection were
      3% and 1%, respectively. We projected costs, morbidity, quality-adjusted survival
      and mortality over 20 years after hiring. The analysis used the healthcare system
      perspective and a 3% annual discount rate. RESULTS: Over 20 years, annual
      screening with TST yielded an expected 2.68 active tuberculosis cases/1000
      workers, versus 2.83 for targeted screening and 3.03 for post-exposure screening
      only. In all cases, annual screening was associated with poorer quality-adjusted
      survival, i.e. lost quality-adjusted life years, compared to targeted or post
      exposure screening only. The annual TST screening strategy yielded an incremental
      cost estimate of $1,717,539 per additional case prevented versus targeted TST
      screening, which in turn cost an incremental $426,678 per additional case
      prevented versus post-exposure TST screening only. With the alternate "higher
      risk" scenario, the annual TST strategy cost an estimated $426,678 per additional
      case prevented versus the targeted TST strategy, which cost an estimated $52,552
      per additional case prevented versus post-exposure TST screening only. In all
      cases, QFT was more expensive than TST, with no or limited added benefit.
      Sensitivity analysis suggested that, even with limited exposure recognition,
      annual screening was poorly cost-effective. CONCLUSIONS: For most North American
      healthcare workers, annual tuberculosis screening appears poorly cost-effective.
      Reconsideration of screening practices is warranted.

PMID- 28514965
TI  - Drug-based vector control: a potential new paradigm.

PMID- 28514964
TI  - HELP! Problems in executing a pragmatic, randomized, stepped wedge trial on the
      Hospital Elder Life Program to prevent delirium in older patients.
AB  - BACKGROUND: A pragmatic, stepped wedge trial design can be an appealing design to
      evaluate complex interventions in real-life settings. However, there are certain
      pitfalls that need to be considered. This paper reports on the experiences and
      lessons learned from the conduct of a cluster randomized, stepped wedge trial
      evaluating the effect of the Hospital Elder Life Program (HELP) in a Dutch
      hospital setting to prevent older patients from developing delirium. METHODS: We
      evaluated our trial which was conducted in eight departments in two hospitals in
      hospitalized patients aged 70 years or older who were at risk for delirium by
      reflecting on the assumptions that we had and on what we intended to accomplish
      when we started, as compared to what we actually realized in the different phases
      of our study. Lessons learned on the design, the timeline, the enrollment of
      eligible patients and the use of routinely collected data are provided
      accompanied by recommendations to address challenges. RESULTS: The start of the
      trial was delayed which caused subsequent time schedule problems. The requirement
      for individual informed consent for a quality improvement project made the
      inclusion more prone to selection bias. Most units experienced major difficulties
      in including patients, leading to excluding two of the eight units from
      participation. This resulted in failing to include a similar number of patients
      in the control condition versus the intervention condition. Data on outcomes
      routinely collected in the electronic patient records were not accessible during
      the study, and appeared to be often missing during analyses. CONCLUSIONS: The
      stepped wedge, cluster randomized trial poses specific risks in the design and
      execution of research in real-life settings of which researchers should be aware
      to prevent negative consequences impacting the validity of their results. Valid
      conclusions on the effectiveness of the HELP in the Dutch hospital setting are
      hampered by the limited quantity and quality of routine clinical data in our
      pragmatic trial. Executing a stepped wedge design in a daily practice setting
      using routinely collected data requires specific attention to ethical review,
      flexibility, a spacious time schedule, the availability of substantial capacity
      in the research team and early checks on the data availability and quality. TRIAL
      REGISTRATION: Netherlands Trial Register, identifier: NTR3842 . Registered on 24
      January 2013.

PMID- 28514963
TI  - Patient-centered primary care for adults at high risk for AUDs: the Choosing
      Healthier Drinking Options In primary CarE (CHOICE) trial.
AB  - BACKGROUND: Most patients with alcohol use disorders (AUDs) never receive alcohol
      treatment, and experts have recommended management of AUDs in primary care. The
      Choosing Healthier Drinking Options In primary CarE (CHOICE) trial was a
      randomized controlled effectiveness trial of a novel intervention for primary
      care patients at high risk for AUDs. This report describes the conceptual and
      scientific foundation of the CHOICE model of care, critical elements of the
      CHOICE trial design consistent with the Template for Intervention Description and
      Replication (TIDieR), results of recruitment, and baseline characteristics of the
      enrolled sample. METHODS: The CHOICE intervention is a multi-contact, extended
      counseling intervention, based on the Chronic Care Model, shared decision-making,
      motivational interviewing, and evidence-based options for managing AUDs, designed
      to be practical in primary care. Outpatients who received care at 3 Veterans
      Affairs primary care sites in the Pacific Northwest and reported frequent heavy
      drinking (>=4 drinks/day for women; >=5 for men) were recruited (2011-2014) into
      a trial in which half of the participants would be offered additional alcohol
      related care from a nurse. CHOICE nurses offered 12 months of patient-centered
      care, including proactive outreach and engagement, repeated brief motivational
      interventions, monitoring with and without alcohol biomarkers, medications for
      AUDs, and/or specialty alcohol treatment as appropriate and per patient
      preference. A CHOICE nurse practitioner was available to prescribe medications
      for AUDs. RESULTS: A total of 304 patients consented to participate in the CHOICE
      trial. Among consenting participants, 90% were men, the mean age was 51 (range 22
      75), and most met DSM-IV criteria for alcohol abuse (14%) or dependence (59%).
      Many participants also screened positive for tobacco use (44%), depression (45%),
      anxiety disorders (30-41%) and non-tobacco drug use disorders (19%). At baseline,
      participants had a median AUDIT score of 18 [Interquartile range (IQR) 14-24] and
      a median readiness to change drinking score of 5 (IQR 2.75-6.25) on a 1-10 Likert
      scale. CONCLUSION: The CHOICE trial tested a patient-centered intervention for
      AUDs and recruited primary care patients at high risk for AUDs, with a spectrum
      of severity, co-morbidity, and readiness to change drinking. Trial registration
      The trial is registered at clinicaltrial.gov (NCT01400581).

PMID- 28514966
TI  - Clinical applications of PD-L1 bioassays for cancer immunotherapy.
AB  - Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to
      predict responses to immunotherapies targeted against PD-L1 and its receptor (PD
      1). Companion tests for evaluating PD-L1 expression as a biomarker of response
      have been developed for many cancer immunotherapy agents. These assays use a
      variety of detection platforms at different levels (protein, mRNA), employ
      diverse biopsy and surgical samples, and have disparate positivity cutoff points
      and scoring systems, all of which complicate the standardization of clinical
      decision-making. This review summarizes the current understanding and ongoing
      investigations regarding PD-L1 expression as a potential biomarker for clinical
      outcomes of anti-PD-1/PD-L1 immunotherapy.

PMID- 28514967
TI  - AT1-receptor response to non-saturating Ang-II concentrations is amplified by
      calcium channel blockers.
AB  - BACKGROUND: Blockers of angiotensin II type 1 receptor (AT1R) and the voltage
      gated calcium channel 1.2 (CaV1.2) are commonly used for treatment of
      hypertension. Yet there is little information about the effect of physiological
      concentrations of angiotensin II (AngII) on AT1R signaling and whether there is a
      reciprocal regulation of AT1R signaling by CaV1.2. METHODS: To elucidate these
      questions, we have studied the Ca2+ signaling response to physiological and
      pharmacological AngII doses in HEK293a cells, vascular smooth muscle cells and
      cardiomyocytes using a Ca2+ sensitive dye as the principal sensor. Intra-cellular
      calcium recordings were performed in presence and absence of CaV1.2 blockers.
      Semi-quantitative imaging methods were used to assess the plasma membrane
      expression of AT1R and G-protein activation. RESULTS: Repeated exposure to
      pharmacological (100 nM) concentrations of AngII caused, as expected, a down
      regulation of the Ca2+ response. In contrast, repeated exposure to physiological
      (1 nM) AngII concentration resulted in an enhancement of the Ca2+ response. The
      up-regulation of the Ca2+ response to repeated 1 nM AngII doses and the down
      regulation of the Ca2+ response to repeated 100 nM Angll doses were not
      accompanied by a parallel change of the AT1R plasma membrane expression. The Ca2+
      response to 1 nM of AngII was amplified in the presence of therapeutic
      concentrations of the CaV1.2 blockers, nifedipine and verapamil, in vascular
      smooth muscle cells, cardiomyocytes and HEK293a cells. Amplification of the AT1R
      response was also observed following inhibition of the calcium permeable
      transient receptor potential cation channels, suggesting that the activity of
      AT1R is sensitive to calcium influx. CONCLUSIONS: Our findings have implications
      for the understanding of hyperactivity of the angiotensin system and for use of
      Ca2+ channel blockers as mono-therapy in hypertension.

PMID- 28514968
TI  - Further evaluation of the NWF filter for the purification of Plasmodium vivax
      infected erythrocytes.
AB  - BACKGROUND: Isolation of Plasmodium-infected red blood cells (iRBCs) from
      clinical blood samples is often required for experiments, such as ex vivo drug
      assays, in vitro invasion assays and genome sequencing. Current methods for
      removing white blood cells (WBCs) from malaria-infected blood are time-consuming
      or costly. A prototype non-woven fabric (NWF) filter was developed for the
      purification of iRBCs, which showed great efficiency for removing WBCs in a pilot
      study. Previous work was performed with prototype filters optimized for
      processing 5-10 mL of blood. With the commercialization of the filters, this
      study aims to evaluate the efficiency and suitability of the commercial NWF
      filter for the purification of Plasmodium vivax-infected RBCs in smaller volumes
      of blood and to compare its performance with that of Plasmodipur(r) filters.
      METHODS: Forty-three clinical P. vivax blood samples taken from symptomatic
      patients attending malaria clinics at the China-Myanmar border were processed
      using the NWF filters in a nearby field laboratory. The numbers of WBCs and iRBCs
      and morphology of P. vivax parasites in the blood samples before and after NWF
      filtration were compared. The viability of P. vivax parasites after filtration
      from 27 blood samples was examined by in vitro short-term culture. In addition,
      the effectiveness of the NWF filter for removing WBCs was compared with that of
      the Plasmodipur(r) filter in six P. vivax blood samples. RESULTS: Filtration of 1
      2 mL of P. vivax-infected blood with the NWF filter removed 99.68% WBCs. The
      densities of total iRBCs, ring and trophozoite stages before and after filtration
      were not significantly different (P > 0.05). However, the recovery rates of
      schizont- and gametocyte-infected RBCs, which were minor parasite stages in the
      clinical samples, were relatively low. After filtration, the P. vivax parasites
      did not show apparent morphological changes. Culture of 27 P. vivax-infected
      blood samples after filtration showed that parasites successfully matured into
      the schizont stage. The WBC removal rates and iRBC recovery rates were not
      significantly different between the NWF and Plasmodipur(r) filters (P > 0.05).
      CONCLUSIONS: When tested with 1-2 mL of P. vivax-infected blood, the NWF filter
      could effectively remove WBCs and the recovery rates for ring- and trophozoite
      iRBCs were high. P. vivax parasites after filtration could be successfully
      cultured in vitro to reach maturity. The performance of the NWF and
      Plasmodipur(r) filters for removing WBCs and recovering iRBCs was comparable.

PMID- 28514969
TI  - Endothelial progenitor cell number is not decreased in 34 children with Juvenile
      Dermatomyositis: a pilot study.
AB  - OBJECTIVE: A pilot study to determine endothelial progenitor cells (EPC) number
      in children with Juvenile Dermatomyositis (JDM). METHODS: After obtaining
      informed consent, the EPC number from 34 fasting children with definite/probable
      JDM at various stages of therapy-initially untreated, active disease on
      medication and clinically inactive, off medication-was compared with 13 healthy
      fasting pediatric controls. The EPC number was determined by fluorescence
      activated cell sorting (FACS), CD34+/VEGFR2+/CD45dim-, and assessed in
      conjunction with clinical variables: disease activity scores (DAS), duration of
      untreated disease (DUD), TNF-alpha allelic polymorphism (A/G) at the promoter
      region of -308, number of nailfold capillary end row loop (ERL) and von
      Willebrand factor antigen (vWF:Ag). Correlations of the EPC numbers with the
      clinical and demographic variables, including DAS Skin (DAS SK), DAS Weakness
      (DAS WK), DAS Total Score, DUD, Cholesterol, triglycerides, High-Density
      Lipoprotein (HDL) and Low-Density Lipoprotein (LDL), and ERL were calculated
      using the Pearson correlation coefficient. Tests of associations of EPC with
      gender (boy vs girl), TNF-alpha-308A allele (GA/AA vs GG), vWF:Ag (categorized by
      specific ABO type) as normal/abnormal were performed, using two-sample T- tests.
      RESULTS: The EPC number for JDM was not significantly different from the healthy
      controls and was not associated with any of the clinical or cardiovascular risk
      factors tested. CONCLUSION: The EPC for JDM were in the normal range, similar to
      adults with DM. These data support the concept that the normal EPC numbers in
      DM/JDM, irrespective of age, differs from adult PM, where they are decreased,
      perhaps reflecting a different pathophysiology.

PMID- 28514970
TI  - Transmission of ST8-USA300 Latin American Variant Methicillin-Resistant
      Staphylococcus aureus on a Neonatal Intensive Care Unit: Recurrent Skin and Soft-
      Tissue Infections as a Marker for Epidemic Community-Associated-MRSA
      Colonization.

PMID- 28514971
TI  - Effects of organic complexed or inorganic Co, Cu, Mn and Zn supplementation
      during a 45-day preconditioning period on productive and health responses of
      feeder cattle.
AB  - This experiment evaluated production and health parameters among cattle offered
      concentrates containing inorganic or organic complexed sources of supplemental
      Cu, Co, Mn and Zn during a 45-day preconditioning period. In total, 90
      Angus*Hereford calves were weaned at 7 months (day -1), sorted by sex, weaning BW
      and age (261+/-2 kg; 224+/-2 days), and allocated to 18 drylot pens (one heifer
      and four steers per pen) on day 0; thus, all pens had equivalent initial BW and
      age. Pens were randomly assigned to receive a corn-based preconditioning
      concentrate containing: (1) Cu, Co, Mn and Zn sulfate sources (INR), (2) Cu, Mn,
      Co and Zn complexed organic source (AAC) or (3) no Cu, Co, Mn and Zn
      supplementation (CON). From day 0 to 45, cattle received concentrate treatments
      (2.7 kg/animal daily, as-fed basis) and had free-choice access to orchardgrass
      (Dactylis glomerata L.), long-stem hay and water. The INR and AAC treatments were
      formulated to provide the same daily amount of Co, Cu, Mn and Zn at a 50-, 16-, 8
      and ninefold increase, respectively, compared with the CON treatment. On day 46,
      cattle were transported to a commercial feedlot, maintained as a single pen, and
      offered a free-choice receiving diet until day 103. Calf full BW was recorded on
      days -1 and 0, 45 and 46, and 102 and 103 for average daily gain (ADG)
      calculation. Liver biopsy was performed on days 0 (used as covariate), 22 and 45.
      Cattle were vaccinated against respiratory pathogens on days 15, 29 and 46. Blood
      samples were collected on days 15, 29, 45, 47, 49, 53 and 60. During
      preconditioning, mean liver concentrations of Co, Zn and Cu were greater (P?0.03)
      in AAC and INR compared with CON. No treatment effects were detected (P?0.17) for
      preconditioning feed intake, ADG or feed efficiency. No treatment effects were
      detected (P?0.48) for plasma concentrations of antibodies against Mannheimia
      haemolytica, bovine viral diarrhea types 1 and 2 viruses. Plasma haptoglobin
      concentrations were similar among treatments (P=0.98). Mean plasma cortisol
      concentration was greater (P?0.04) in CON compared with INR and AAC. No treatment
      effects were detected (P?0.37) for cattle ADG during feedlot receiving. Hence,
      INR and AAC increased liver concentrations of Co, Zn and Cu through
      preconditioning, but did not impact cattle performance and immunity responses
      during preconditioning and feedlot receiving.

PMID- 28514972
TI  - The effect of Tetraneura ulmi L. galling process on the activity of amino acid
      decarboxylases and the content of biogenic amines in Siberian elm tissues.
AB  - Tetraneura ulmi (L.), a member of Eriosomatinae subfamily, is one of the gall
      forming aphids occurring on elms. Sap-sucking behaviour of founding mothers
      results in the formation of new plant organs. This study documents the changes in
      the content of plant biogenic amines (putrescine, cadaverine, spermidine,
      tryptamine, spermine and histamine) and key enzymes of their biosynthesis: lysine
      decarboxylase (LDC), tyrosine decarboxylase and ornithine decarboxylase (ODC) in
      galls and other parts of Siberian elm (Ulmus pumila L.) leaves during the galling
      process. The direction and intensity of these changes for particular amines and
      enzymes were dependent on the stage of gall development and part of the galling
      leaf. Generally, the amine content tended to increase in gall tissues during the
      1st and 2nd period of the galling process and decreased in later phases. LDC and
      ODC activities were markedly enhanced, especially in gall tissues at the initial
      stage of the galling process.

PMID- 28514973
TI  - Olfactory evaluation of boar taint: effect of factors measured at slaughter and
      link with boar taint compounds.
AB  - There is a commitment by the European pig sector to ban surgical castration of
      male piglets in the European Union in 2018. One alternative to castration is to
      raise entire male pigs, with an increased risk of boar taint. A field study was
      performed to: (1) evaluate inter- and intra-farm variation in boar taint
      prevalence, (2) investigate factors measured at slaughter influencing boar taint
      and (3) evaluate the relationship between sensorial scoring by a trained panel
      and the concentration of boar taint components. From 34 farms, neck fat samples
      were collected from all entire male pigs in at least two slaughter batches per
      farm (78 batches; 9167 animals). In addition to olfactory boar taint analysis,
      data were also collected on fresh skin lesions (score 0 to 3) at the slaughter
      line, slaughter weight, lean meat percentage, duration of transport, time spent
      in lairage, total delivery duration, day length, shortening of days and outdoor
      mean temperature. Using the hot iron method, neck fat samples were scored (eight
      point scale) for boar taint. Average boar taint prevalence (score >=3) was 5.6+/
      2.5% and the mean difference between the maximum and minimum prevalence per farm
      was 4.3+/-3.2%. Androstenone (AND), skatole (SKA) and indole concentrations were
      measured for a subset (n=254) of the samples. According to binomial univariate
      mixed models, entire male pigs with a higher skin lesion score had higher odds of
      having boar taint (P=0.031), as did fatter entire male pigs (P<0.001). In the
      binomial multivariate mixed model lean meat percentage (P<0.001) and outdoor mean
      temperature (P=0.005) remained as only significant factors. Based on our results,
      we can conclude that these statistically significant at least partially influence
      the prevalence of boar taint. According to the binomial univariate mixed models
      SKA concentration in liquid fat seems a better predictor for boar taint than AND.
      There were no significant synergetic effects between boar taint compounds.

PMID- 28514974
TI  - Additional thoughts on teaching and prescribing MAOIs.

PMID- 28514975
TI  - Courttney Cooper: mapping the interior.

PMID- 28514976
TI  - Working Despite Having Influenza-Like Illness: Results of An Anonymous Survey of
      Healthcare Providers Who Care for Transplant Recipients.
AB  - OBJECTIVE To compare the rates of and reasons for presenteeism associated with
      influenza-like illness (ILI) among healthcare professionals (HCPs) caring for
      hospitalized inpatient transplant recipients and internal medicine patients.
      DESIGN We designed a 10-question anonymous survey in which ILI was defined as
      fever (>37.8 degrees C) and cough and/or sore throat and ILI B was defined as
      fever (>37.8 degrees C) or cough or sore throat; both definitions were considered
      in the absence of another known cause. SETTING Tertiary-care center. PARTICIPANTS
      Physicians, advanced practice providers (APPs) and nurses. INTERVENTION Survey
      deployed at peak of influenza activity in 2016. MEASUREMENTS Rates of ILI,
      presenteeism, wearing masks, and time away due to ILI. RESULTS Of 707 HCPs
      surveyed, 286 (40%) responded; 15 (5.2%) reported having ILI, and 73 (25.5%)
      reported having ILI B in the preceding 2 weeks. Presenteeism rates were 92% in
      both groups of HCPs and were higher among women (adjusted odds ratio [AOR], 2.64;
      95% CI, 1.23-5.71; P=.01) and those <=40 years old (AOR, 1.92; 95% CI, 1.03-3.68;
      P=.04). Healthcare professionals who cared for transplant recipients and female
      HCPs were more likely to wear masks (AOR, 2.13; 95% CI, 1.05-3.40; P=.04 for
      transplant recipients and AOR, 3.96; 95% CI, 1.35-11.63; P=.01 for female HCPs).
      Nurses were more likely than physicians and APPs to take time off (AOR, 3.33; 95%
      CI, 1.10-10.09; P=.03.) CONCLUSIONS Presenteeism among HCPs with ILI is common,
      including among those caring for transplant recipients. Nonpunitive systems
      should encourage HCPs not to work with ILI and to wear masks to prevent spread of
      infections. Infect Control Hosp Epidemiol 2017;38:966-969.

PMID- 28514977
TI  - Cross-cultural adaptation and validation of the Newest Vital Sign (NVS) health
      literacy instrument in general population and highly educated samples of
      Brazilian adults.
AB  - OBJECTIVE: The present work aimed at cross-cultural adaptation and validation of
      the health literacy assessment tool Newest Vital Sign (NVS) in general population
      (GP) and highly educated (HE) samples of Brazilian adults. DESIGN: An expert
      committee reviewed the translation and back-translation processes and the
      cultural adaptation. The construct validity was analysed with confirmatory factor
      analysis and via associations with features of the study population. SETTING: The
      final validation test was performed in two different populations from Londrina, a
      large town in southern Brazil. SUBJECTS: Brazilian adults: GP (adult clients of
      community pharmacies; n 189) and HE (public school teachers; n 301). RESULTS: The
      tool under validation showed good cross-cultural adaptation and internal
      consistency, with Cronbach's alpha of 0.75 for GP and 0.74 for HE. Confirmatory
      factor analysis showed acceptable models and identified two independent factors
      according to the relationship between components and numeracy for both GP and HE
      data. According to the Brazilian Portuguese version of the NVS instrument (NVS
      BR), 48.7 % of GP and 33.5 % of HE presented adequate health literacy; this
      condition was inversely associated with age for both populations and directly
      correlated with educational level for GP. CONCLUSIONS: The NVS-BR showed good
      validity in two different populations of Brazilian adults and can be considered
      an alternative in screening for inadequate health literacy.

PMID- 28514978
TI  - Jugular-infused methionine, lysine and branched-chain amino acids does not
      improve milk production in Holstein cows experiencing heat stress.
AB  - Poor utilization of amino acids contributes to losses of milk protein yield in
      dairy cows exposed to heat stress (HS). Our objective was to test the effect of
      essential amino acids on milk production in lactating dairy cows exposed to short
      term HS conditions. To achieve this objective, 12 multiparous, lactating Holstein
      cows were assigned to two environments (thermoneutral (THN) or HS) from days 1 to
      14 in a split-plot type cross-over design. All cows received 0 g/day of essential
      amino acids from days 1 to 7 (negative control (NC)) followed by an intravenous
      infusion of l-methionine (12 g/day), l-lysine (21 g/day), l-leucine (35 g/day), l
      isoleucine (15 g/day) and l-valine (15 g/day, methionine, lysine and branched
      chain amino acids (ML+BCAA)) from days 8 to 14. The basal diet was composed of
      ryegrass silage and hay, and a concentrate mix. This diet supplied 44 g of
      methionine, 125 g of lysine, 167 g of leucine, 98 g of isoleucine and 109 g of
      valine per day to the small intestine of THN cows. Temperature-humidity index was
      maintained below 66 for the THN environment, whereas the index was maintained
      above 68, peaking at 76, for 14 continuous h/day for the HS environment. Heat
      stress conditioning increased the udder temperature from 37.0 degrees C to 39.6
      degrees C. Cows that received the ML+BCAA treatment had greater p.m. rectal and
      vaginal temperatures (0.50 degrees C and 0.40 degrees C, respectively), and
      respiration rate (8 breaths/min) compared with those on the NC treatment and
      exposed to a HS environment. However, neither NC nor ML+BCAA affected rectal or
      vaginal temperatures and respiration rates in the THN environment. Compared with
      THN, the HS environment reduced dry matter intake (1.48 kg/day), milk yield (2.82
      kg/day) and milk protein yield (0.11 kg/day). However, compared with NC, the
      ML+BCAA treatment increased milk protein percent by 0.07 points. For the THN
      environment, the ML+BCAA treatment increased concentrations of milk urea
      nitrogen. For the HS environment, the ML+BCAA treatment decreased plasma
      concentrations of arginine, ornithine and citrulline; however, differences were
      not observed for the THN environment. In summary, HS elicited expected changes in
      production; however, infusions of ML+BCAA failed to increase milk protein yield.
      Lower dry matter intake and greater heat load in response to ML+BCAA contributed
      to the lack of response in milk production in HS cows. The ML+BCAA treatment may
      have reduced the breakdown of muscle protein in heat-stressed cows.

PMID- 28514979
TI  - Determination of a Cutoff Time Point for Prophylactic Exchange of Central Venous
      Catheters for Prevention of Central Venous Catheter-Related Bloodstream
      Infections in Patients with Hematological Malignancies.

PMID- 28514980
TI  - Evaluation of benzimidazole resistance status in Ascaridia galli.
AB  - Susceptability of Ascaridia galli to benzimidazole (BZ) was investigated using
      faecal egg count reduction test (FECRT), in ovo larval development test (LDT) and
      genetic markers (mutations at codons 167, 198 and 200 of beta-tubulin gene). Six
      flocks (F1-F6) of a commercial laying hen farm with different number of exposure
      to BZ were recruited. The FECR was calculated by analyzing individual faeces (F1,
      F2, F4 and F5) before and 10 days after treatment. The LDT was performed on
      parasite eggs from pooled samples from F1 to F6 and LC50 and LC99 were
      calculated. DNA was extracted from 120 worms and sequenced for beta-tubulin gene.
      In all flocks, the FECRs were above 95% (lower CI above 90%). No significant
      difference was observed (p > 0.05) among obtained LC50 (F1/F4 and F2/F5 vs F3/F6)
      in the LDT. However, LC50 and LC99 were higher than suggested values for
      declaration of resistance in other nematode species. No variation was observed in
      codon positions involved in BZ resistance. Overall, our results indicated lack of
      evidence of resistance to BZ in A. galli. More research is needed to confirm
      these results and to further optimize the existing tools for detection and
      monitoring of anthelmintic resistance in A. galli.

PMID- 28514981
TI  - Essential Lessons in a Potential Sarin Attack Disaster Plan for a Resource
      Constrained Environment.
AB  - Sarin is a potent nerve agent chemical weapon that was originally designed for
      military purposes as a fast-acting anti-personnel weapon that would kill or
      disable large numbers of enemy troops. Its potent toxicity, ease of deployment,
      and rapid degradation allow for rapid deployment by an attacking force, who can
      safely enter the area of deployment a short while after its release. Sarin has
      been produced and stockpiled by a number of countries, and large quantities of it
      still exist despite collective agreements to cease manufacture and destroy
      stockpiles. Sarin's ease of synthesis, which is easily disseminated across the
      Internet, increases the risk that terrorist organizations may use sarin to attack
      civilians. Sarin has been used in a number of terrorist attacks in Japan, and
      more recently in attacks in the Middle East, where nonmilitary organizations have
      led much of the disaster relief and provision of medical care. In the present
      article, we examine and discuss the available literature on sarin's historical
      use, delivery methods, chemical properties, mechanism of action, decontamination
      process, and treatment. We present a management guideline to assist with the
      recognition of an attack and management of victims by medical professionals and
      disaster relief organizations, specifically in resource-constrained and austere
      environments. (Disaster Med Public Health Preparedness. 2018;12:249-256).

PMID- 28514982
TI  - EVALUATION CRITERIA OF PATIENT AND PUBLIC INVOLVEMENT IN RESOURCE ALLOCATION
      DECISIONS: A LITERATURE REVIEW AND QUALITATIVE STUDY.
AB  - OBJECTIVES: We developed specific evaluation criteria to assess patient and
      public involvement in resource allocation decisions in health care. METHODS: We
      reviewed the literature from health and other sectors relevant to stakeholder
      involvement and conducted twenty-seven key informant interviews with stakeholders
      knowledgeable about patient and public involvement in Canadian drug resource
      allocation decisions. We used an inductive qualitative thematic approach to
      analyze the interviews with codes and categories developed directly from
      individuals' interview transcripts. RESULTS: Integrating respondents' comments
      and the literature review, we identified nine evaluation criteria of patient and
      the public involvement in healthcare resource allocation decision making: clarity
      regarding rationale and roles of patient and public members, sufficient support,
      adequate representation of relevant views, fair decision-making processes,
      legitimacy of committee processes, adequate opportunity for participation,
      meaningful degree of participation, noticeable effect on decisions, and
      considerations of the efficiency of patient and public involvement. CONCLUSIONS:
      Our results will help to develop methods to evaluate patient and public
      involvement in healthcare decision making.

PMID- 28514983
TI  - Adverse effects of consuming high fat-sugar diets on cognition: implications for
      understanding obesity.
AB  - There is increasing evidence for important roles of key cognitive processes,
      including attention, memory and learning, in the short-term decision making about
      eating. There is parallel evidence that people who are overweight or obese tend
      to perform worse on a variety of cognitive tasks. In this review, the evidence
      for these two ideas is summarised and then the idea that overconsumption of
      Western-style high-fat (HF)-high-sugar diets may underlie the association between
      obesity and poorer cognitive performance is explored. In particular, evidence in
      animals and human subjects that repeated consumption of HF or HF and sugar (HFS)
      diets leads to specific impairments in the functioning of the hippocampus, which
      underpin the consequent changes in cognition is summarised. These findings lead
      into the vicious cycle model (VCM), which suggests that these cognitive changes
      have knock-on negative effects for future appetite control, and evidence that
      altered hippocampal function is also associated with impaired appetite control is
      explored. The review concludes that there is consistent evidence in the animal
      literature and emerging evidence from human studies that supports this VCM. It is
      also noted, however, that to date studies lack the nutritional specificity needed
      to be able to translate these basic research findings into clear nutritional
      effects, and concludes that there is an urgent need for additional research to
      clarify the precise nature of the apparent effects of consuming HFS diets on
      cognition.

PMID- 28514984
TI  - Alternate Mediterranean diet score is positively associated with skeletal muscle
      mass index in middle-aged adults.
AB  - Researches have suggested Mediterranean diet might lower the risk of chronic
      diseases, but data on skeletal muscle mass (SMM) are limited. This community
      based cross-sectional study examined the association between the alternate
      Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75
      years in Guangzhou, China. General information and habitual dietary information
      were assessed in face-to-face interviews conducted during 2008-2010 and 3 years
      later. The aMDS was calculated by summing the dichotomous points for the items of
      higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio
      of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the
      whole body, limbs, arms and legs were measured using dual-energy X-ray
      absorptiometry during 2011-2013. After adjusting for potential covariates, higher
      aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2,
      kg/m2) at all of the studied sites in males (all P trend<0.05). The multiple
      covariate-adjusted SMI means were 2.70 % (whole body), 2.65 % (limbs), 2.50 %
      (arms) and 2.70 % (legs) higher in the high (v. low) category aMDS in males (all
      P<0.05). In females, the corresponding values were 1.35 % (P trend=0.03), 1.05,
      0.52 and 1.20 %, (P trend>0.05). Age-stratified analyses showed that the
      favourable associations tended to be more pronounced in the younger subjects aged
      less than the medians of 59.2 and 62.2 years in females and males (P
      interaction>0.10). In conclusion, the aMDS shows protective associations with SMM
      in Chinese adults, particularly in male and younger subjects.

PMID- 28514985
TI  - New technology in nutrition research and practice.
AB  - Recent technology advancements are aiding the development of scientific
      discoveries and changing the methods by which we perform research. In order to
      gain full benefits for human health, it will be important to embrace these new
      technologies in nutrition research while also acknowledging their limitations.
      The present issue covers a range of technological approaches that impact on
      public health nutrition and molecular nutrition. The critical appraisal of these
      approaches in the context of nutrition research makes this issue a timely and
      pertinent addition to the scientific literature.

PMID- 28514986
TI  - Lorenz Oken (1779-1851): Naturphilosophie and the reform of natural history.
AB  - The paper focuses on the work of Lorenz Oken (1779-1851) in an attempt to make
      sense of the role played by Romantic Naturphilosophie in the development of
      natural history in Germany at the turn of the nineteenth century. It first
      focuses on the role played by Schelling and his Wurzburg circle in the
      development of Oken's early views on natural history, then reconstructs Oken's
      mature programme for a reform of animal classification.

PMID- 28514987
TI  - A systematic review of the prevalence and predictors of the double burden of
      malnutrition within households.
AB  - Recently, increasing attention has been paid to the emergence of the double
      burden of malnutrition within households. We provide an overview of the
      literature regarding this phenomenon by reviewing previous studies of the
      prevalence of double-burden households and associated factors together with the
      research methods used. Studies were identified from the electronic databases
      PubMed and Web of Science, using the same search terms for both. A total of
      thirty-five articles met the eligibility criteria, and 367 sets of prevalence
      data were extracted. In all, thirty-four articles were published in 2000 or
      later; twenty-four used secondary data and twenty-five focused on mother-child
      pairs. The ages of children varied from 0 to 19 years. All the studies used BMI
      as a nutritional indicator for adults. For children, height-for-age was most
      frequently used, whereas weight-for-age, weight-for-height and BMI-for-age were
      also used in multiple studies. The reported national prevalence of double-burden
      households varied from 0.0 to 26.8 % by country and year; however, few studies
      were directly comparable, because of differences in the combinations of
      undernourished and overweight persons, age ranges, nutritional indicators and cut
      off points. Whereas many focused on African countries, a few involved Asian
      countries. Although urban residence, income and education were frequently
      assessed, the role of intermediate factors in nutritional status, such as diet
      and physical activity, remains unclear. It is recommended that future studies use
      comparable indicators and cut-off points, involve Asian countries, and
      investigate individual diet and physical activity.

PMID- 28514988
TI  - How Latina mothers navigate a 'food swamp' to feed their children: a photovoice
      approach.
AB  - OBJECTIVE: To understand how mothers who recently migrated from Central America
      to the USA feed their children in a neighbourhood saturated with unhealthful food
      choices ('food swamp') and to formulate a mother-driven plan of action to
      facilitate their acquisition of foods. Design/Setting/Subjects We purposively
      sampled mothers with children (<10 years old) who were recent immigrants/refugees
      from Central America and lived in a 'food swamp' neighbourhood. We used the
      photovoice approach to elicit textual data from thirty in-depth interviews, a
      participatory workshop, and visual data from photographs. Analyses were guided by
      the Social Ecological Framework and Social Cognitive Theory to identify barriers,
      facilitators and strategies that support parents in feeding their children.
      RESULTS: Mothers valued foods that they considered to be 'traditional' and
      'healthful'. They navigated their food retail environment looking for these foods
      (of good quality and well-priced). Food values were reinforced by pre-migration
      food customs and culture, health professionals' advice and, in some cases, by the
      desire to avoid conflict with their children. The neighbourhood food environment
      could directly influence children's food preferences and often created conflict
      between what the child wanted to eat and the foods that mothers valued. Mothers
      in this 'food swamp' wanted to be engaged in addressing the selection of foods
      offered in schools and in neighbourhood food venues to reflect their own food
      values. CONCLUSIONS: These mothers' feeding choices were influenced directly by
      their food values, and indirectly by the neighbourhood and school food
      environments via their children's preferences.

PMID- 28514989
TI  - Help-seeking intentions for anxiety among older adults.
AB  - Mental health practices are not working for older people with anxiety in
      residential care, as there is a persistent lack of recognition and treatment.
      This suggests that alternative ways of reaching and meeting the needs of this
      population need to be explored. One possibility involves enabling older adults
      themselves to seek help. The current work explored various factors impacting on
      help-seeking behaviours. In total, 105 participants from independent living units
      in a residential care setting completed a questionnaire focusing on attitudes and
      stigma towards anxiety, likelihood to seek help, help-seeking barriers and
      literacy around the symptoms of anxiety. Participants in the main did not hold
      negative attitudes towards other people with anxiety, despite concerns that other
      people could view them negatively if they were experiencing anxiety. Barriers to
      help-seeking included: difficulties recognising physical anxiety symptoms as
      being indicative of anxiety; the effectiveness of treatments; costs;
      misdiagnosis; privacy; medication usage and the associated side-effects; and,
      uneasiness about the skills and knowledge of health professionals. Although
      concerns were not held by all participants, the fact remains that anxiety is
      largely undiagnosed and untreated for this population and these stoppages to
      appropriate care must be addressed.

PMID- 28514990
TI  - Prevalence of porA pseudogene deletion among Neisseria gonorrhoeae isolates
      referred to the UK's Gonococcal Resistance to Antimicrobials Surveillance
      Program.
AB  - porA pseudogene-negative Neisseria gonorrhoeae isolates produce false-negative
      results when examined by polymerase chain reaction (PCR) with porA pseudogene
      targets. In the present study, 533 representative gonococcal isolates received in
      2011 via the Gonococcal Resistance to Antimicrobials Surveillance Program were
      examined to determine the prevalence of porA-negative isolates. Less than 0.4%
      (2/533) of isolates were found to be reproducibly negative with the porA real
      time PCR but were confirmed as N. gonorrhoeae with molecular, biochemical and
      immunological confirmatory tests. Sequencing revealed both isolates contained the
      Neisseria meningitidis porA gene. Low prevalence indicates that although these
      isolates do not present a major public health problem, microbiologists should
      remain vigilant.

PMID- 28514991
TI  - Pregnant young women's attitudes about microbicides: the anticipated influence of
      the grandmother and father of the baby on microbicide use.
AB  - Grandmothers and fathers of the baby may influence pregnant women's microbicide
      use. Pregnant young women's attitudes about grandmothers' and fathers' role in
      decision-making and their involvement in microbicide use were assessed.
      Participants (n=108) had a mean age of 20.2 years. The majority anticipated that
      the grandmother, father or both would have a decision-making role. Greater
      grandmother involvement in microbicide use was significantly associated with
      being younger, having no reproductive tract infection or contraceptive-ring-use
      history. Greater father involvement in use was associated with being in a
      relationship with him. Strategies for engaging grandmothers and fathers in
      microbicide use should be developed.

PMID- 28514992
TI  - Sexual difficulties faced by men in the Solomon Islands: a mixed-methods study.
AB  - : Background To date there has been little research into men's sexual and
      reproductive health in Pacific Island countries. The aim of this study was to
      describe men's sexual difficulties and barriers to their seeking reproductive
      health care in the Solomon Islands. METHODS: The study included qualitative
      inquiry (17 individual interviews and three focus group discussions with a total
      of 21 men) and a quantitative quasi-randomised quota sample household survey
      (n=400). The prevalence of sexual difficulties and potential risk factors, such
      as chronic diseases, health risk behaviours, depression and psychological
      distress were measured using standardised questions translated into pidgin.
      RESULTS: The most commonly self-reported sexual difficulties were premature
      ejaculation (39.5%), low sexual desire (29.0%), orgasm difficulty (27.3%) and
      erectile difficulty (4.3%). More than half (56%) of the men experienced at least
      one sexual difficulty. Relatively few men (7.3%) had ever sought professional
      health care for reproductive health problems, and 15.4% of men preferred to use
      kastom (traditional) medicine for sexual problems. Multivariate analysis revealed
      that comorbid non-communicable diseases (NCDs), low health-related quality of
      life and dissatisfaction with sexual relationships were independently correlated
      with sexual difficulties. Contrary to expectations, self-reported psychological
      distress was inversely associated with these difficulties. In general, the
      insights gained from in-depth interviews validated the survey findings.
      CONCLUSION: This study adds the first data on symptoms of sexual dysfunction
      among men in the Solomon Islands and is one of few studies from the Pacific
      region. The findings strongly suggest the need for comprehensive health services
      that are gender-specific and sensitive to the sexual difficulties of Islander
      men.

PMID- 28514993
TI  - Beyond diagnosis and survivorship: findings from a mixed-methods study of a
      community-based cancer support service.
AB  - This consumer-led research investigated the client experiences and the individual
      and community benefits of a community-based cancer support service operating in a
      regional setting. The study included cross-sectional surveys, focus group
      discussions and key-informant interviews. In total, 114 clients, 28 carers and 20
      therapists were surveyed; three client focus groups were conducted and five
      directors and staff were interviewed. For many clients and carers, the warm
      welcome experienced at first contact sets the tone for a long-term association
      with the organisation. The feeling of being cared for extends to the broader
      community and living with cancer becomes more than survivorship. Integral to the
      organisational model are opportunity (second-hand) shops that enable subsidised
      complementary therapies and other services, offer a way of giving back and assist
      disadvantaged community members. The organisational model has benefits, not only
      for people living with cancer and their families, but also for the wider
      community.

PMID- 28514994
TI  - Active syphilis and its association with HIV and sexual risk behaviours in a
      multicity sample of men who have sex with men and transgender women in Peru.
AB  - : Background Syphilis in Peru is heavily concentrated in men who have sex with
      men (MSM) and transgender women (TGW). The aim of the present study was to
      understand the risk factors for active syphilis infection among MSM and TGW in
      Peru. METHODS: Independent correlates suggestive of active syphilis infection
      were examined to better understand risk factors for syphilis in MSM and TGW, with
      separate analyses conducted based on location and among TGW. In 2011, 5101 MSM
      and TGW completed both self-report surveys and HIV and syphilis testing in five
      Peruvian cities. RESULTS: Overall, 261 (5.1%) MSM and TGW met the criteria for
      active syphilis, with higher prevalence in Lima than elsewhere (7.0% vs 3.0%) and
      in TGW than in MSM (10.7% vs 4.2%). Significant independent correlates of active
      syphilis infection differed greatly by location. In Lima, they included being HIV
      infected (aware or unaware of status), being a TGW, being a high school graduate,
      engaging in receptive anal intercourse, no recent sex with a female partner and
      having had any symptomatic sexually transmissible infection, including syphilis,
      in the previous 6 months. Outside Lima, the independent correlates included being
      HIV-infected and unaware of status, engaging in recent sex work, no recent sex
      with a female partner and age 35-44 years. Among TGW, independent correlates of
      active syphilis included being HIV-infected (aware or unaware of status), a
      recent syphilis diagnosis in the previous 6 months and recent drug use.
      CONCLUSION: The findings of the present study support the need not only for
      combined HIV and syphilis screening, but also for increased screening and
      treatment of syphilis in MSM and TGW populations. Stratified analyses suggest
      different syphilis epidemics throughout the country and in TGW, yet being HIV
      infected and aware were consistently associated with active syphilis, suggesting
      higher syphilis risk in HIV-infected MSM and TGW.

PMID- 28514995
TI  - Tobacco smoking and sexual difficulties among Australian adults: a cross
      sectional study.
AB  - : Background Few studies have examined smoking and female sexual difficulties.
      The aim of this study was to investigate the association between current tobacco
      smoking and sexual difficulties in Australian men and women. METHODS: Data for
      this study came from the Second Australian Study of Health and Relationships
      (2012-13), which includes a representative sample of 18427 sexually active
      Australian adults (aged 16-69 years). The main study and outcome measures were
      tobacco smoking and sexual difficulties. A multiple logistic regression analysis
      was conducted to adjust for potential confounders. RESULTS: Male heavy smokers
      (>20 cigarettes per day) were significantly more likely than non-smokers to have
      trouble keeping an erection [adjusted odds ratio (AOR) 4.14, 95% confidence
      interval (CI) 1.87-9.20; P<0.0001], lack interest in having sex (AOR 2.18, 95% CI
      1.20-3.97; P=0.011), have anxiety about performance (AOR 2.46, 95% CI 1.24-4.86;
      P=0.010) and be unable to come to orgasm (AOR=2.81, 95% CI 1.23-6.42; P=0.015).
      Female smokers were also significantly more likely than non-smokers to not find
      sex pleasurable (AOR 1.48, 95% CI 1.05-2.07; P=0.025); and light female smokers
      were significantly more likely than non-smokers to be unable to come to orgasm
      (AOR=1.44, 95% CI 1.05-1.98; P=0.025). CONCLUSIONS: Current tobacco smoking was
      associated with sexual difficulties in both men and women. For women, even light
      smoking was associated with not finding sex pleasurable and being unable to come
      to orgasm.

PMID- 28514996
TI  - Post-autopsy computed tomography. Pros and cons in a firearm death.
AB  - Many studies have focused on the importance of post-mortem computed tomography
      (PMCT) prior to or in substitution of standard forensic autopsies in case of
      firearm death. However, due to the fact that PMCT is not routinely performed in
      all countries, in cases of death abroad it can happen that a CT scan is performed
      only after a first autopsy. A case of post-mortem re-examination, including the
      external examination and a post-autopsy computed tomography (PACT), of a gunshot
      victim of homicide in a foreign country is presented, and the pros and cons of
      imaging in post-autopsy setting are discussed. PACT could be a tool for carrying
      out more complete investigations and for obtaining information on bone injuries
      and foreign bodies trapped within peripheral soft tissues that can be re-analyzed
      after the arrival of the first autopsy report. Given that the value of
      information derived may be strongly influenced by the previously performed
      autopsy, in order to process the definitive considerations it is necessary to
      compare and interpret the data obtained through PACT with the results of the
      first autopsy, and to continue the international cooperation effort and the
      application of international guidelines in order to share information at the
      repatriation of the corpse.

PMID- 28514997
TI  - The prevalence of food allergy and other allergic diseases in early childhood in
      a population-based study: HealthNuts age 4-year follow-up.
AB  - BACKGROUND: The HealthNuts study previously reported interim prevalence data
      showing the highest prevalence of challenge-confirmed food allergy in infants
      internationally. However, population-derived prevalence data on challenge
      confirmed food allergy and other allergic diseases in preschool-aged children
      remain sparse. OBJECTIVE: This study aimed to report the updated prevalence of
      food allergy at age 1 year from the whole cohort, and to report the prevalence of
      food allergy, asthma, eczema, and allergic rhinitis at age 4 years. METHODS:
      HealthNuts is a population-based cohort study with baseline recruitment of 5276
      one-year-old children who underwent skin prick test (SPT) to 4 food allergens and
      those with detectable SPT results had formal food challenges. At age 4 years,
      parents completed a questionnaire (81.3% completed) and those who previously
      attended the HealthNuts clinic at age 1 year or reported symptoms of a new food
      allergy were invited for an assessment that included SPT and oral food
      challenges. Data on asthma, eczema, and allergic rhinitis were captured by
      validated International Study of Asthma and Allergies in Childhood
      questionnaires. RESULTS: The prevalence of challenge-confirmed food allergy at
      age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut
      allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI,
      0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset
      peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma
      was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to
      17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty
      percent to 50% of this population-based cohort experienced symptoms of an
      allergic disease in the first 4 years of their life. CONCLUSIONS: Although the
      prevalence of food allergy decreased between age 1 year and age 4 years in this
      population-based cohort, the prevalence of any allergic disease among 4-year-old
      children in Melbourne, Australia, is remarkably high.

PMID- 28514998
TI  - Affibody Molecules in Biotechnological and Medical Applications.
AB  - Affibody molecules are small (6.5-kDa) affinity proteins based on a three-helix
      bundle domain framework. Since their introduction 20 years ago as an alternative
      to antibodies for biotechnological applications, the first therapeutic affibody
      molecules have now entered clinical development and more than 400 studies have
      been published in which affibody molecules have been developed and used in a
      variety of contexts. In this review, we focus primarily on efforts over the past
      5 years to explore the potential of affibody molecules for medical applications
      in oncology, neurodegenerative, and inflammation disorders, including molecular
      imaging, receptor signal blocking, and delivery of toxic payloads. In addition,
      we describe recent examples of biotechnological applications, in which affibody
      molecules have been exploited as modular affinity fusion partners.

PMID- 28514999
TI  - Severe hypovitaminosis D in active tuberculosis patients and its predictors.
AB  - BACKGROUND & AIMS: Tuberculosis (TB) patients have a significant vitamin D
      deficiency (VDD) endemic, which may be closely related to the onset and progress
      of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing
      challenge in recent years. However, the influence of DM on TB and the possible
      mechanism are still uncertain. We carried out this study to identify the
      nutritional status of vitamin D (VD) in TB patients in a northern city in China
      (latitude 36 degrees  N) and investigate the possible predictors of severe
      vitamin D deficiency (SVDD). METHODS: A cross-sectional study including 461
      active TB patients (192 with and 269 without DM) were randomly selected from
      Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25
      hydroxyvitamin D [25(OH)D], and investigated the association between
      sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial
      TB signs and symptoms (TB score) and VD status. Multivariate logistic regression
      analysis was used to define the possible predictors of SVDD. RESULTS: The median
      serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383
      (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8
      ng/mL]. The variables associated with serum 25(OH)D concentrations were DM,
      outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB
      score had nearly 5 fold higher risk of having SVDD compared with those in mild
      subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity
      level also increased the odds of SVDD, while DM and high fish consumption showed
      protect effects. CONCLUSIONS: Severe hypovitaminosis D is prevalent in active TB
      patients, and the main predictors of SVDD were severe TB score, low outdoor
      activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated
      with increased risk of TB in DM.

PMID- 28515000
TI  - Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death.
AB  - The endoplasmic reticulum (ER) and mitochondria cannot be considered as static
      structures, as they intimately communicate, forming very dynamic platforms termed
      mitochondria-associated membranes (MAMs). In particular, the ER transmits proper
      Ca2+ signals to mitochondria, which decode them into specific inputs to regulate
      essential functions, including metabolism, energy production and apoptosis. Here,
      we will describe the different molecular players involved in the transfer of Ca2+
      ions from the ER lumen to the mitochondrial matrix and how modifications in both
      ER-mitochondria contact sites and Ca2+ signaling can alter the cell death
      execution program.

PMID- 28515001
TI  - In vitro extracellular matrix accumulation of nasal and articular chondrocytes
      for intervertebral disc repair.
AB  - Chondrocyte based regenerative therapies for intervertebral disc repair such as
      Autologous Disc Cell Transplantation (ADCT, CODON) and allogeneic juvenile
      chondrocyte implantation (NuQu(r), ISTO Technologies) have demonstrated good
      outcomes in clinical trials. However concerns remain with the supply demand
      reconciliation and issues surrounding immunoreactivity which exist for allogeneic
      type technologies. The use of stem cells is challenging due to high growth factor
      requirements, regulatory barriers and differentiation towards a stable phenotype.
      Therefore, there is a need to identify alternative non-disc cell sources for the
      development and clinical translation of next generation therapies for IVD
      regeneration. In this study, we compared Nasal Chondrocytes (NC) as a non-disc
      alternative chondrocyte source with Articular Chondrocytes (AC) in terms of cell
      yield, morphology, proliferation kinetics and ability to produce key
      extracellular matrix components under 5% and 20% oxygen conditions, with and
      without exogenous TGF-beta supplementation. Results indicated that NC maintained
      proliferative capacity with high amounts of sGAG and lower collagen accumulation
      in the absence of TGF-beta supplementation under 5% oxygen conditions.
      Importantly, osteogenesis and calcification was inhibited for NC when cultured in
      IVD-like microenvironmental conditions. The present study provides a rationale
      for the exploration of nasal chondrocytes as a promising, potent and clinically
      feasible autologous cell source for putative IVD repair strategies.

PMID- 28515002
TI  - Electrocardiographic QRS-T angle and the risk of incident silent myocardial
      infarction in the Atherosclerosis Risk in Communities study.
AB  - BACKGROUND: Silent myocardial infarction (SMI) accounts for about half of the
      total number of MIs, and is associated with poor prognosis as is clinically
      documented MI (CMI). The electrocardiographic (ECG) spatial QRS/T angle has been
      a strong predictor of cardiovascular outcomes. Whether spatial QRS/T angle also
      is predictive of SMI, and the easy-to-obtain frontal QRS/T angle will show
      similar association are currently unknown. METHODS: We examined the association
      between the spatial and frontal QRS/T angles, separately, with incident SMI among
      9498 participants (mean age 54years, 57% women, and 20% African-American), who
      were free of cardiovascular disease at baseline (visit 1, 1987-1989) from the
      Atherosclerosis Risk in Communities (ARIC) study. Incident SMI was defined as MI
      occurring after the baseline until visit 4 (1996-1998) without CMI. The frontal
      plane QRS/T angle was defined as the absolute difference between QRS axis and T
      axis. Values greater than the sex-specific 95th percentiles of the QRS/T angles
      were considered wide (abnormal). RESULTS: A total of 317 (3.3%) incident SMIs
      occurred during a 9-year median follow-up. In a model adjusted for demographics,
      cardiovascular risk factors and potential confounders, both abnormal frontal (HR
      2.28, 95% CI 1.58-3.29) and spatial (HR 2.10, 95% CI 1.44-3.06) QRS/T angles were
      associated with an over 2-fold increased risk of incident SMI. Similar patterns
      of associations were observed when the results were stratified by sex.
      CONCLUSIONS: Both frontal and spatial QRS/T angles are predicative of SMI
      suggesting a potential use for these markers in identifying individuals at risk.

PMID- 28515003
TI  - Reverse atrial electrical remodeling induced by cardiac resynchronization
      therapy.
AB  - PURPOSE: Cardiac resynchronization therapy (CRT) has been shown to improve left
      atrial function; however the effect on reverse electrical remodeling has been
      poorly evaluated. We hypothesized that CRT might induce reverse atrial electrical
      remodeling manifesting in the surface ECG as a shortening in P-wave duration.
      METHODS: Patients with CRT and more than 92% biventricular pacing at minimum
      follow-up of 1 year were included in the analysis. Those with prior history of
      atrial fibrillation (AF) were excluded. Data were recorded for clinical,
      echocardiographic and ECG variables prior to implant and at least 12 months post
      implantation. Semiautomatic calipers and scanned ECGs at 300 DPI maximized * 8
      were used to measure P-wave duration and diagnose advanced interatrial block
      (aIAB) during sinus rhythm. The occurrence of AF was assessed through analyses of
      intracardiac electrograms and clinical presentations. RESULTS: 41 patients were
      included in the study with mean age of 67.4 +/-9.6 years, 71% were male, left
      atrial diameter 41.1 +/- 8.5 mm and LV EF 28.5 +/- 6.5%. Over a mean follow up of
      55 months, a significant reduction in P-wave duration (142.7 ms vs. 133.1 ms; p <
      0.001) was noted. The presence of aIAB was significantly reduced (36% vs. 17%; p
      = 0.03). The incidence of new onset AF was 36%. Time to AF onset after CRT
      implantation was not influenced by a reduction in P-wave duration. CONCLUSION:
      CRT induces atrial reverse electrical remodeling manifested as a reduction in P
      wave duration. Larger studies are needed to determine the impact on AF incidence
      after CRT implantation.

PMID- 28515004
TI  - Animal breeding strategies can improve meat quality attributes within entire
      populations.
AB  - The contribution of animal breeding to changes in animal performance is well
      documented across a range of species. Once genetic variation in a trait exists,
      then breeding to improve the characteristics of that trait is possible, if so
      desired. Considerable genetic variation exists in a range of meat quality
      attributes across a range of species. The genetic variation that exists for meat
      quality is as large as observed for most performance traits; thus, within a well
      structured breeding program, rapid genetic gain for meat quality could be
      possible. The rate of genetic gain can be augmented through the integration of
      DNA-based technologies into the breeding program; such DNA-based technologies
      should, however, be based on thousands of DNA markers dispersed across the entire
      genome. Genetic and genomic technologies can also have beneficial impact outside
      the farm gate as a tool to segregate carcasses or meat cuts based on expected
      meat quality features.

PMID- 28515005
TI  - Dynamics of a True Moving Bed separation process: Linear model identification and
      advanced process control.
AB  - The control of Simulated Moving Bed (SMB) units is challenging due to their
      complex dynamic behaviour and the difficulty of measuring their main properties.
      Furthermore, for the SMB units, the transfer function identification when the
      unit is operating at its optimal point is not easy to be done through the usual
      way. This work presents the development of a novel strategy to identify transfer
      functions of TMB/SMB and its application on classical linear model predictive
      controllers (MPC). However, for the process in study, due its unique dynamics,
      only the identification of the linear model is not enough to solve its control
      problem. Therefore, it is proposed a modification in the MPC prediction, that
      consists in a strategy based on a switching system where the most adequate
      transfer function is employed in the controller to overcome the problems related
      with the process dynamic behaviour. The results show that the used methodology
      enables the easy identification of transfer functions at the process optimal
      operating point and that the MPC can control the process in both the servo and
      regulator problem cases. It is also showed that the transfer function identified
      can be applied in the control of a SMB unit with four columns, under its optimal
      conditions.

PMID- 28515006
TI  - Two-dimensional multi-heart cutting centrifugal partition chromatography-liquid
      chromatography for the preparative isolation of antioxidants from Edelweiss
      plant.
AB  - The Edelweiss plant has been recognized as a very valuable source of anti-aging
      principles due to its composition of antioxidants compounds: leontopodic acid A
      and 3,5-dicaffeoylquinic acid. In this work, off-line multi-heart cutting CPC-LC
      separation was set up at industrial scale in order to isolate and produce new
      high quality reference material of these two antioxidants from Edelweiss. For
      this purpose, CPC and HPLC methods were developed and optimized at laboratory
      scale and a comprehensive CPCxHPLC analysis of the crude extract was established.
      Thereby, the CPC method led to a first separation of the target compounds
      according to their partition coefficient in the solvent system and the HPLC
      method was performed on the recovered fractions to lead to a second separation. A
      2D CPCxHPLC plot was established in order to know the fractions to select at the
      industrial scale. Then, the CPC and HPLC methods were transferred at industrial
      scale and the multi-heart cutting CPC-LC was performed in off-line mode. Using
      CPC with methyl ter-butyl ether-water 1:1 (v/v) solvent system and LC with Denali
      C18 column, 2g of crude extract sample were injected and leontopodic acid A and
      3,5-dicaffeoylquinic acid were recovered with purity over 97%. The compounds were
      identified by MS and NMR.

PMID- 28515007
TI  - Effects of maternal traumatic distress on family functioning and child mental
      health: An examination of Southeast Asian refugee families in the U.S.
AB  - BACKGROUND: The psychological effects of trauma are well-documented among refugee
      adults and children alone, yet less research has attended to the
      intergenerational transmission of trauma within refugee families. Additionally,
      there is considerable diversity between refugee populations as well as within
      group variation in the experiences and effects of refugee trauma. OBJECTIVE: The
      current study examines the longitudinal effects of maternal traumatic distress on
      family functioning and child mental health outcomes among Southeast Asian refugee
      women and their adolescent children. Given the potential for variation in these
      effects, we also explore group differences in these relationships by ethnicity
      and child nativity. METHODS: Longitudinal data were collected from a random
      sample of 327 Southeast Asian refugee mothers and their children in the United
      States. We employed structural equation modeling to examine associations between
      latent variables representing maternal traumatic distress, family functioning,
      and child mental health outcomes (i.e., depressive symptoms, antisocial and
      delinquent behavior, and school problems). We then tested for group differences
      in these associations by ethnicity (Cambodian and Vietnamese subgroups) and child
      nativity (U.S.-born and foreign-born children). RESULTS: We found maternal
      traumatic distress was indirectly linked to child mental health outcomes, and
      that child nativity was associated with these paths while ethnicity was not. For
      foreign-born children, maternal traumatic distress was associated with diminished
      family functioning a year later, which was associated with increased school
      problems at the two-year mark. Maternal traumatic distress was indirectly
      associated with depressive symptoms and antisocial and delinquent behavior,
      respectively, after accounting for family functioning. For all children, weaker
      family functioning was significantly associated with poorer mental health.
      CONCLUSIONS: Findings suggest that refugee parents' trauma can adversely affect
      family relationships and the mental health of children. Interventions that
      address parental trauma and support intergenerational relationships may enhance
      mental health within refugee communities for future generations.

PMID- 28515008
TI  - Localization and distribution of gonadal proteins in the oviparous lizard
      Sceloporus aeneus (Squamata: Phrynosomatidae).
AB  - Among vertebrates, several specific proteins are involved in the function and
      development of gonads. Several genes such as SOX9, FOXL2, DDX4, IFITM3, and
      DPPA3, are active during embryonic differentiation and maintain their expression
      in adult tissues, playing important roles in the function and development of the
      line cell, where these are produced. Among reptiles, molecular mechanisms for sex
      differentiation have been analyzed in turtles, crocodiles, and some lizards,
      while in adult stages such studies are scarce. The aim of this study was to
      locate and analyze the distribution of important gonadal proteins in adult and
      embryonic ovaries and testes of the oviparous lizard Sceloporus aeneus (Squamata:
      Phrynosomatidae). Adult specimens and embryos of the lizard S. aeneus were
      collected in Milpa Alta, a suburb located Southwest of Mexico City. Expression of
      gonadal proteins was analyzed using immunofluorescent staining and confocal
      microscopy. Our results showed that SOX9 is located in Sertoli cells of embryonic
      and adult testes. FOXL2 is expressed in follicular cells of adult ovaries. DDX4
      and IFITM3 are located in germ line cells as well as in follicular cells of adult
      ovaries. DPPA3 was observed in somatic and germ line cells of adult and embryonic
      gonads. Our observations show that important molecules of vertebrate ovaries and
      testes are conserved in S. aeneus and it is suggested that these may have a
      similar role during gonadal development and function.

PMID- 28515009
TI  - Transfer learning on fused multiparametric MR images for classifying
      histopathological subtypes of rhabdomyosarcoma.
AB  - This paper presents a deep-learning-based CADx for the differential diagnosis of
      embryonal (ERMS) and alveolar (ARMS) subtypes of rhabdomysarcoma (RMS) solely by
      analyzing multiparametric MR images. We formulated an automated pipeline that
      creates a comprehensive representation of tumor by performing a fusion of
      diffusion-weighted MR scans (DWI) and gadolinium chelate-enhanced T1-weighted MR
      scans (MRI). Finally, we adapted transfer learning approach where a pre-trained
      deep convolutional neural network has been fine-tuned based on the fused images
      for performing classification of the two RMS subtypes. We achieved 85% cross
      validation prediction accuracy from the fine-tuned deep CNN model. Our system can
      be exploited to provide a fast, efficient and reproducible diagnosis of RMS
      subtypes with less human interaction. The framework offers an efficient
      integration between advanced image processing methods and cutting-edge deep
      learning techniques which can be extended to deal with other clinical domains
      that involve multimodal imaging for disease diagnosis.

PMID- 28515011
TI  - Sustained Activity Encoding Working Memories: Not Fully Distributed.
AB  - Working memory (WM) is the ability to remember and manipulate information for
      short time intervals. Recent studies have proposed that sustained firing encoding
      the contents of WM is ubiquitous across cortical neurons. We review here the
      collective evidence supporting this claim. A variety of studies report that
      neurons in prefrontal, parietal, and inferotemporal association cortices show
      robust sustained activity encoding the location and features of memoranda during
      WM tasks. However, reports of WM-related sustained activity in early sensory
      areas are rare, and typically lack stimulus specificity. We propose that robust
      sustained activity that can support WM coding arises as a property of association
      cortices downstream from the early stages of sensory processing.

PMID- 28515010
TI  - Aberrant Network Activity in Schizophrenia.
AB  - Brain dynamic changes associated with schizophrenia are largely equivocal, with
      interpretation complicated by many factors, such as the presence of therapeutic
      agents and the complex nature of the syndrome itself. Evidence for a brain-wide
      change in individual network oscillations, shared by all patients, is largely
      equivocal, but stronger for lower (delta) than for higher (gamma) bands. However,
      region-specific changes in rhythms across multiple, interdependent, nested
      frequencies may correlate better with pathology. Changes in synaptic excitation
      and inhibition in schizophrenia disrupt delta rhythm-mediated cortico-cortical
      communication, while enhancing thalamocortical communication in this frequency
      band. The contrasting relationships between delta and higher frequencies in
      thalamus and cortex generate frequency mismatches in inter-regional connectivity,
      leading to a disruption in temporal communication between higher-order brain
      regions associated with mental time travel.

PMID- 28515012
TI  - Breast cancer and exercise: The role of adiposity and immune markers.
AB  - Currently, breast cancer accounts for a quarter of all cancers and 15% of cancer
      specific deaths amongst females. The global occurrence of breast cancer has
      increased in the last decade whilst the mortality rate has decreased. Exercise
      can be beneficial to breast cancer patients through changes in adiposity and
      immune responses. Even though there is some evidence supporting the improvement
      of fat metabolism and immune function after an exercise program in breast cancer,
      randomized controlled studies are limited and require further comprehensive
      analysis in this population group. Herein, we identify the known effects of
      exercise programs on adiposity and immunological markers which can improve breast
      cancer outcomes.

PMID- 28515013
TI  - Atomic force microscopy: From red blood cells to immunohaematology.
AB  - Atomic force microscopy (AFM) offers complementary imaging modes that can provide
      morphological and structural details of red blood cells (RBCs), and characterize
      interactions between specific biomolecules and RBC surface antigen. This review
      describes the applications of AFM in determining RBC health by the observation of
      cell morphology, elasticity and surface roughness. Measurement of interaction
      forces between plasma proteins and antibodies against RBC surface antigen using
      the AFM also brought new information to the immunohaematology field. With
      constant improvisation of the AFM in resolution and imaging time, the reaction of
      RBC to changes in the physico-chemistry of its environment and the presence of
      RBC surface antigen specific-biomolecules is achievable.

PMID- 28515015
TI  - Collateral damage and the criminalisation of drug use.

PMID- 28515016
TI  - Determination of the absolute configuration of a novel tetrasubstituted
      isoindolinone by vibrational circular dichroism.
AB  - The absolute configuration of a recently prepared asymmetric 3,3-disubstituted
      isoindolinone (ethyl 2-benzyl-3-oxo-1-(3-oxobutyl)isoindoline-1-carboxylate),
      possessing highly promising pharmaceutical activity, has been determined by means
      of VCD spectroscopy and DFT calculations. The great flexibility of the molecule
      reduces to a few relevant conformers, all contributing in the same way to the
      shape of the VCD spectrum for the carbonyl stretching region. Two of the three CO
      groups of the molecule interact with each other during the stretching vibration,
      thus providing a non-conservative VCD couplet whose signature, together with the
      VCD sign of the third CO stretching mode, unequivocally determines the absolute
      configuration of the molecule, which is found to be (S) for the (-) optical
      isomer.

PMID- 28515017
TI  - Fatty acid-binding protein3 expression in BeWo cells, a human placental
      choriocarcinoma cell line.
AB  - Cellular uptake of long chain fatty acids in human placental trophoblasts is
      thought to be mediated by several membrane- and cytoplasmic fatty acid-binding
      proteins (FABP). FABP3 was shown to be involved in long chain polyunsaturated
      fatty acids (LCPUFA) uptake in human trophoblastic choriocarcinoma cells, BeWo as
      the uptake of arachidonic acid,20:4n-6 (ARA) was decreased in FABP3-knockdown
      BeWo cells. However, the regulation of expression of FABP3 in these cells is not
      yet well known. The aim of the present study was to examine the FABP3 expression
      by LCPUFAs, insulin and LXR agonists in BeWo cells. Among all these fatty acids
      tested, only ARA dose-dependently stimulated the expression of FABP3 protein in
      these cells after 24h incubation while other fatty acids had no such effect. In
      addition, LXR agonist and insulin dose-dependently increased FABP3 protein
      expression in these cells after 24h incubation. Insulin-stimulated FABP3 protein
      expression was accompanied with an increased arachidonic acid uptake.
      Differentiated BeWo cells had lesser expression of FABP3 protein than in the
      undifferentiated cells as the cellular differentiation state was measured by hCG
      production. In preeclamptic placental tissue, lowered expression of FABP3 protein
      was observed compared with those in normal pregnancy. All these data indicate
      that FABP3 may in be part involved in ARA uptake in these cells and its
      expression may be regulated by ARA, insulin, LXR and the state of cellular
      differentiation.

PMID- 28515014
TI  - HIV and the criminalisation of drug use among people who inject drugs: a
      systematic review.
AB  - BACKGROUND: Mounting evidence suggests that laws and policies prohibiting illegal
      drug use could have a central role in shaping health outcomes among people who
      inject drugs (PWID). To date, no systematic review has characterised the
      influence of laws and legal frameworks prohibiting drug use on HIV prevention and
      treatment. METHODS: Consistent with PRISMA guidelines, we did a systematic review
      of peer-reviewed scientific evidence describing the association between
      criminalisation of drug use and HIV prevention and treatment-related outcomes
      among PWID. We searched MEDLINE, Embase, SCOPUS, PsycINFO, Sociological
      Abstracts, CINAHL, Web of Science, and other sources. To be included in our
      review, a study had to meet the following eligibility criteria: be published in a
      peer-reviewed journal or presented as a peer-reviewed abstract at a scientific
      conference; examine, through any study design, the association between an a
      priori set of indicators related to the criminalisation of drugs and HIV
      prevention or treatment among PWID; provide sufficient details on the methods
      followed to allow critical assessment of quality; be published or presented
      between Jan 1, 2006, and Dec 31, 2014; and be published in the English language.
      FINDINGS: We identified 106 eligible studies comprising 29 longitudinal, 49 cross
      sectional, 22 qualitative, two mixed methods, four mathematical modelling
      studies, and no randomised controlled trials. 120 criminalisation indicators were
      identified (range 1-3 per study) and 150 HIV indicators were identified (1-5 per
      study). The most common criminalisation indicators were incarceration (n=38) and
      street-level policing (n=39), while the most frequent HIV prevention and
      treatment indicators were syringe sharing (n=35) and prevalence of HIV infection
      among PWID (n=28). Among the 106 studies included in this review, 85 (80%)
      suggested that drug criminalisation has a negative effect on HIV prevention and
      treatment, 10 (9%) suggested no association, five (5%) suggested a beneficial
      effect, one (1%) suggested both beneficial and negative effects, and five (5%)
      suggested both null and negative effects. INTERPRETATION: These data confirm that
      criminalisation of drug use has a negative effect on HIV prevention and
      treatment. Our results provide an objective evidence base to support numerous
      international policy initiatives to reform legal and policy frameworks
      criminalising drug use. FUNDING: Canadian Institutes of Health Research and US
      National Institutes of Health.

PMID- 28515018
TI  - Plasma levels of the endocannabinoid anandamide, related N-acylethanolamines and
      linoleic acid-derived oxylipins in patients with migraine.
AB  - There is evidence that patients with migraine have deficient levels of the
      endogenous cannabinoid receptor ligand anandamide (AEA). It is not known,
      however, if this is a localised or generalised phenomenon. In the present study,
      levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived
      oxylipins have been measured in the blood of 26 healthy women and 38 women with
      migraine (26 with aura, 12 without aura) who were matched for age and body-mass
      index. Blood samples were taken on two occasions: the first sample near the start
      of the menstrual cycle (when present) and the second approximately fourteen days
      later. For a subset of migraine patients, two additional blood samples were
      taken, one during a migraine attack and one approximately 1 month later (to be at
      the same stage in the menstrual cycle, when present). NAEs and oxylipins were
      measured by liquid chromatography coupled to mass spectrometry. Twenty-nine
      lipids were quantified, of which 16 were found to have a high reproducibility of
      measurement. There were no significant differences in the levels of AEA, the
      related NAEs stearoylethanolamide and oleoylethanolamide or any of the nine
      linoleic acid-derived oxylipins measured either between migraine patients with
      vs. without aura, or between controls and migraine patients (after stratification
      to take into account whether or not the individuals had regular menstruation
      cycles) in either of the first two samples. Levels of linoleoylethanolamide were
      lower in the patients with vs. without aura on the second sample but not in the
      first sample, but the biological importance of this finding is unclear. Due to
      time-dependent increases in their concentrations ex vivo prior to centrifugation,
      AEA and oleoylethanolamide levels in the samples collected during migraine
      attacks were not analysed, but for the other fourteen lipids, there were no
      significant differences in plasma concentrations during migraine vs. one month
      later. It is concluded that migraine is not associated with a generalised (as
      opposed to localised) deficiency in these lipids.

PMID- 28515019
TI  - Serum polyunsaturated fatty acid metabolites as useful tool for screening
      potential biomarker of colorectal cancer.
AB  - The biomarker identification of cancer is benefit for early detection and less
      invasion. Polyunsaturated fatty acid (PUFA) metabolite as inflammatory mediators
      can affect progression and treatment of cancer. In this work, the serum was
      collected from colorectal cancer patients and healthy volunteers, and then we
      tested the change of serum PUFA metabolites in both of them by ultra-high
      performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Of the
      158 PUFA and their metabolites, we found that abnormal change of 2, 3-dinor-8-iso
      PGF2alpha, 19-HETE and 12-keto-LTB4 from arachidonic acid were observed in
      colorectal cancer patients. Meanwhile, 9-HODE and 13-HODE from linoleic acid were
      significant lower in colorectal cancer patients. Our data suggested that some
      PUFA metabolites might be used as a potential biomarker of colorectal cancer,
      which might provide assistance in clinical diagnosis and treatment.

PMID- 28515020
TI  - Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index
      more than high-dose eicosapentaenoic acid.
AB  - BACKGROUND: Recent studies suggest that eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acids have distinct effects on cardiometabolic risk
      factors. The Omega-3 Index (O3I), which is calculated as the proportion of EPA
      and DHA in red blood cell (RBC) membranes, has been inversely associated with the
      risk of coronary heart diseases and coronary mortality. The objective of this
      study was to compare the effects of EPA and DHA supplementation on the O3I in men
      and women with abdominal obesity and subclinical inflammation. METHODS: In a
      double-blind controlled crossover study, 48 men and 106 women with abdominal
      obesity and subclinical inflammation were randomized to a sequence of three
      treatment phases: 1-2.7g/d of EPA, 2-2.7g/d of DHA, and 3-3g/d of corn oil (0g of
      EPA+DHA). All supplements were provided as 3*1g capsules for a total of 3g/d. The
      10-week treatment phases were separated by nine-week washouts. RBC membrane fatty
      acid composition and O3I were assessed at baseline and the end of each phase.
      Differences in O3I between treatments were assessed using mixed models for
      repeated measures. RESULTS: The increase in the O3I after supplementation with
      DHA (+5.6% compared with control, P<0.0001) was significantly greater than after
      EPA (+3.3% compared with control, P<0.0001; DHA vs. EPA, P<0.0001). Compared to
      control, DHA supplementation decreased (-0.8%, P<0.0001) while EPA increased
      (+2.5%, P<0.0001) proportion of docosapentaenoic acid (DPA) in RBCs (DHA vs. EPA,
      P<0.0001). The baseline O3I was higher in women than in men (6.3% vs. 5.8%,
      P=0.011). The difference between DHA and EPA in increasing the O3I tended to be
      higher in men than in women (+2.6% vs. +2.2% respectively, P for the treatment by
      sex interaction=0.0537). CONCLUSIONS: The increase in the O3I is greater with
      high dose DHA supplementation than with high dose EPA, which is consistent with
      the greater potency of DHA to modulate cardiometabolic risk factors. The extent
      to which such differences between EPA and DHA in increasing the O3I relates to
      long-term cardiovascular risk needs to be investigated in the future.

PMID- 28515021
TI  - Sulforaphene, an isothiocyanate present in radish plants, inhibits proliferation
      of human breast cancer cells.
AB  - BACKGROUND: Isothiocyanates derived from the Brassicaceae plants possess
      chemopreventive and anticancer activities. One of them is sulforaphene (SF),
      which is abundant in Rhapanus sativus seeds. The underlying mechanism of its
      anticancer activity is still underexplored. PURPOSE: SF properties make it an
      interesting candidate for cancer prevention and therapy. Thus, it is crucial to
      characterize the mechanism of its activity. STUDY DESIGN: We investigated the
      mechanism of antiproliferative activity of SF in breast cancer cells differing in
      growth factor receptors status and lacking functional p53. METHODS: Viability of
      SKBR-3 and MDA-MB-231 breast cancer cells treated with SF was determined by SRB
      and clonogenic assays. Cell cycle, cell death and oxidative stress were analyzed
      by flow cytometry or microscopy. The levels of apoptosis and autophagy markers
      were assessed by immunoblotting. RESULTS: SF efficiently decreased the viability
      of breast cancer cells, while normal cells (MCF10A) were less sensitive to the
      analyzed isothiocyanate. SF induced G2/M cell cycle arrest, as well as disturbed
      cytoskeletal organization and reduced clonogenic potential of the cancer cells.
      SF induced apoptosis in a concentration-dependent manner which was associated
      with the oxidative stress, mitochondria dysfunction, increased Bax:Bcl2 ratio and
      ADRP levels. SF also potentiated autophagy which played a cytoprotective role.
      CONCLUSIONS: SF exhibits cytotoxic activity against breast cancer cells even at
      relatively low concentrations (5-10uM). This is associated with induction of the
      cell cycle arrest and apoptosis. SF might be considered as a potent anticancer
      agent.

PMID- 28515023
TI  - Corrigendum: Chikusetsusaponin IVa methyl ester induces G1 cell cycle arrest,
      triggers apoptosis and inhibits migration and invasion in ovarian cancer cells.
      Phytomedicine, 2016, 23(13): 1555-1565.

PMID- 28515022
TI  - SOS response in bacteria: Inhibitory activity of lichen secondary metabolites
      against Escherichia coli RecA protein.
AB  - BACKGROUND: RecA is a bacterial multifunctional protein essential to genetic
      recombination, error-prone replicative bypass of DNA damages and regulation of
      SOS response. The activation of bacterial SOS response is directly related to the
      development of intrinsic and/or acquired resistance to antimicrobials. Although
      recent studies directed towards RecA inactivation via ATP binding inhibition
      described a variety of micromolar affinity ligands, inhibitors of the DNA binding
      site are still unknown. PURPOSE: Twenty-seven secondary metabolites classified as
      anthraquinones, depsides, depsidones, dibenzofurans, diphenyl-butenolides,
      paraconic acids, pseudo-depsidones, triterpenes and xanthones, were investigated
      for their ability to inhibit RecA from Escherichia coli. They were isolated in
      various Chilean regions from 14 families and 19 genera of lichens. METHODS: The
      ATP hydrolytic activity of RecA was quantified detecting the generation of free
      phosphate in solution. The percentage of inhibition was calculated fixing at
      100uM the concentration of the compounds. Deeper investigations were reserved to
      those compounds showing an inhibition higher than 80%. To clarify the mechanism
      of inhibition, the semi-log plot of the percentage of inhibition vs. ATP and vs.
      ssDNA, was evaluated. RESULTS: Only nine compounds showed a percentage of RecA
      inhibition higher than 80% (divaricatic, perlatolic, alpha-collatolic, lobaric,
      lichesterinic, protolichesterinic, epiphorellic acids, sphaerophorin and
      tumidulin). The half-inhibitory concentrations (IC50) calculated for these
      compounds were ranging from 14.2uM for protolichesterinic acid to 42.6uM for
      sphaerophorin. Investigations on the mechanism of inhibition showed that all
      compounds behaved as uncompetitive inhibitors for ATP binding site, with the
      exception of epiphorellic acid which clearly acted as non-competitive inhibitor
      of the ATP site. Further investigations demonstrated that epiphorellic acid
      competitively binds the ssDNA binding site. Kinetic data were confirmed by
      molecular modelling binding predictions which shows that epiphorellic acid is
      expected to bind the ssDNA site into the L2 loop of RecA protein. CONCLUSION: In
      this paper the first RecA ssDNA binding site ligand is described. Our study sets
      epiphorellic acid as a promising hit for the development of more effective RecA
      inhibitors. In our drug discovery approach, natural products in general and
      lichen in particular, represent a successful source of active ligands and
      structural diversity.

PMID- 28515024
TI  - Knowledge, attitude, and practice towards blood donation among health care
      providers in hospitals at Bahir Dar City, Ethiopia.
AB  - Like other sub-Saharan Africa, in Ethiopia there is a shortage of adequate and
      safe blood supplies. Health care providers are potential resource and promoter of
      voluntary blood donation. This study was conducted to determine the knowledge,
      attitude and practice towards blood donation among health care providers in Bahir
      Dar City, Ethiopia. Paper based questionnaire was distributed to 276 health care
      providers from May 01 to June 30, 2016. Overall, 42.8% had donated blood at least
      once. Of these, males accounted for 60%. The median age of blood donors was 26
      years. Voluntary-unpaid donation was 21.2%. Overall, 75.5% health care providers
      were knowledgeable. The levels of knowledge were significantly different among
      different disciplines (One-way ANOVA; F=69.7; P=0.004). Males were more
      knowledgeable than females (P<0.05). The overall favorable attitude was 78.6%.
      Previous practice of blood donation determined the odds of favorable attitude to
      be a future regular voluntary-unpaid blood donor (OR: 5.7, 95% CI: 3.2-10.4).
      Majority of health care providers had adequate knowledge and favorable attitude.
      However, voluntary-unpaid donation practice (21.1%) was lower compared to 100%
      target of voluntary-unpaid donation. There should be motivation packages to
      enhance voluntary-unpaid blood donation among health care professionals.

PMID- 28515025
TI  - Priority-setting and feasibility of health information exchange for primary care
      patients with intellectual disabilities: A modified Delphi study.
AB  - OBJECTIVE: Accurate health information exchange (HIE) is fragile in healthcare
      for patients with intellectual disabilities (ID), threatening the health outcomes
      for this patient group. In conjunction with a group of experts, we aimed to
      identify the principal actions and organisational factors facilitating HIE for
      primary care patients with ID and to assess their perceived feasibility in daily
      practice. METHODS: We conducted a two-round modified Delphi study with Dutch GPs
      (n=22), support workers (n=18) and ID physicians (n=20). In an extensive set of
      61 items covering actions and organisational factors, experts ranked items in
      order of importance and rated their feasibility. RESULTS: Agreement was reached
      on the importance of 22 actions and eight organisational factors, of which 82%
      were deemed (very) feasible in daily practice. Experts stressed the importance of
      listed actions and factors being implemented simultaneously and remarked that
      further priority should be based on contextual demands. CONCLUSION AND PRACTICE
      IMPLICATIONS: This study indicates the principal actions and organisational
      factors for HIE regarding primary care patients with ID. The set can be used as a
      practical guide to optimise inter-professional cooperation and arrange the
      distribution of HIE roles and responsibilities in relation to this patient group.

PMID- 28515026
TI  - Corrigendum to ' Development of a prediction model for child maltreatment
      recurrence in Japan: A historical cohort study using data from a Child Guidance
      Center' Child Abuse & Neglect 59 (2016) 55-65.

PMID- 28515028
TI  - Augmentation of the infraorbital rim in orthognathic surgery.
AB  - Mid-face augmentation via a Le Fort I osteotomy is a commonly performed
      operation. Advancement of the upper jaw and associated structures (nose, lower
      cheek areas) can certainly improve function as well as facial aesthetics and
      harmony. Often, in patients with severe mid-face deficiency, hypoplasia of the
      maxilla extends all the way up to the infraorbital rims. The receding
      infraorbital rim contributes to the negative vector of the globes. In patients
      with this level of mid-face hypoplasia, while advancing the maxilla at the Le
      Fort I level satisfies all of the requirements for orthognathic surgery, the
      deficient infraorbital rim remains unchanged and can actually accentuate the
      negative vector of the globes. This article explains our approach in augmentation
      of the deficient infraorbital rim using alloplastic silicone implants at the time
      of a Le Fort I osteotomy.

PMID- 28515027
TI  - Early Versus Delayed Invasive Strategies in High-Risk Non-ST Elevation Acute
      Coronary Syndrome Patients - A Systematic Literature Review and Meta-Analysis of
      Randomised Controlled Trials.
AB  - RATIONALE: It is unclear whether it is beneficial to perform angiography and/or
      percutaneous coronary intervention (PCI) as an early or delayed invasive strategy
      amongst high-risk non-ST elevation acute coronary syndrome (NSTEACS) patients.
      OBJECTIVE: To determine whether an early invasive strategy could further reduce
      recurrent myocardial infarction (MI) and early mortality compared to a delayed
      invasive strategy. METHODS AND RESULTS: We searched MEDLINE, CINAHL and SCOPUS
      and performed a meta-analysis of nine RCTs with a total of 5274 patients. No
      statistically significant difference in recurrent MI (RR=0.56, 95% CI 0.17-1.87,
      p=0.35), early mortality (RR=0.81, 95% CI 0.62-1.05, p=0.11) and major bleeding
      (RR=0.85, 95% CI 0.66-1.09, p=0.21) was found between groups. A statistically
      significant reduction in recurrent ischaemia was found amongst patients treated
      with an early invasive strategy (RR 0.45, 95% CI 0.26-0.78, p=0.004). Subgroup
      analysis for recurrent MI showed a statistically significant reduction in risk
      amongst patients treated <24hours compared to>=24hours (RR=0.31, 95% CI 0.11
      0.89, p=0.03). CONCLUSION: This study suggests that an early invasive strategy
      may not further reduce recurrent MI and early mortality, but may significantly
      reduce recurrent ischaemia. However, the recurrent MI endpoint was associated
      with heterogeneity due to inconsistent MI definitions and strategy timings
      amongst the included trials. Furthermore, subgroup analysis demonstrated a
      significant reduction in recurrent MI amongst patients treated <24hours.
      Therefore, large clinical trials with consistent inclusion criteria are required
      to confirm whether intervention within 24hours reduces the rate of spontaneous
      and post-discharge recurrent MI. Future studies with long-term follow-up data are
      required to detect relevant differences in early mortality. Currently, it appears
      that stabilised high-risk NSTEACS patients may be safely delayed up to 24hours
      before undergoing an early invasive strategy.

PMID- 28515029
TI  - Tolvaptan Treatment in Children with Chronic Hyponatremia due to Inappropriate
      Antidiuretic Hormone Secretion: A Report of Three Cases
AB  - Hyponatremia is the most common electrolyte disorder among hospitalized patients
      and it is sometimes considered as a poor outcome predictor. Its correction is
      thus indicated, even in asymptomatic patients. The conventional treatment
      consists of fluid restriction in presence of euvolemia or hypervolemia; loop
      diuretics are used in some hypervolemic conditions such as cardiac heart failure,
      liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic
      solutions are administered in hypovolemic conditions. The utilization of
      demeclocycline and urea is not indicated in pediatric ages due to lack of data on
      their toxicity and poor tolerance. Recently, a new therapeutic option has been
      developed, a class of non-peptide arginine vasopressin receptor antagonists
      called vaptans. Tolvaptan is the only such agent approved in Europe for the
      treatment of hyponatremia caused by syndrome of inappropriate antidiuretic
      hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been
      approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are
      so far available in paediatric patients, since only one trial has been registered
      in Europe which includes children and adolescents, but this trial is still
      ongoing. Here, we report three children with chronic hyponatremia due to SIADH in
      which tolvaptan has been used successfully.

PMID- 28515030
TI  - Congenital Central Hypothyroidism Caused by a Novel Thyroid-Stimulating Hormone
      Beta Subunit Gene Mutation in Two Siblings.
AB  - Congenital central hypothyroidism (CCH) is a very rare disease. Alterations in
      pituitary development genes as well as mutations of immunoglobulin superfamily
      member 1 and transducin beta-like protein 1 can result in CCH and multiple
      pituitary hormone deficiencies. However, mutations of the thyrotropin-releasing
      hormone receptor or thyroid-stimulating hormone-beta (TSHB) gene are responsible
      for isolated CCH. In this paper, we present the cases of two siblings with a
      novel mutation of TSHB. Direct sequencing of the coding regions and exon/intron
      boundaries of the TSHB gene revealed two homozygous nucleotides changes. One of
      them was c.40A>G (rs10776792) which is a very common variation that is also seen
      in healthy individuals, the other was c.94G>A at codon 32 of exon 2 which
      resulted in a change from glutamic acid to lysine (p.E32K). Both patients were
      homozygous and the parents were heterozygous.

PMID- 28515032
TI  - WITHDRAWN: Bilateral painless testicular mass, acute uveitis and annular
      cutaneous lesions: an unusual presentation of sarcoidosis and literature review.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 28515031
TI  - Phenotypic Variability in a Family with Acrodysostosis Type 2 Caused by a Novel
      PDE4D Mutation Affecting the Serine Target of Protein Kinase-A Phosphorylation.
AB  - Acrodysostosis is a very rare congenital multisystem condition characterized by
      skeletal dysplasia with severe brachydactyly, midfacial hypoplasia, and short
      stature, varying degrees of intellectual disability, and possible resistance to
      multiple G protein-coupled receptor signalling hormones. Two distinct subtypes
      are differentiated: acrodysostosis type 1 resulting from defects in protein
      kinase type 1-alpha regulatory subunit and acrodysostosis type 2 caused by
      mutations in phosphodiesterase 4D (PDE4D). Most cases are sporadic. We report on
      a rare multigenerational familial case of acrodysostosis type 2 due to a novel
      autosomal dominantly inherited PDE4D mutation. A 3.5-year-old boy presented with
      short stature, midfacial hypoplasia, severe brachydactyly, developmental delay,
      and behavioural problems. Laboratory investigations revealed mild thyrotropin
      resistance. His mother shared some characteristic features, such as midfacial
      hypoplasia and severe brachydactyly, but did not show short stature, intellectual
      disability or hormonal resistance. Genetic analysis identified the identical,
      novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in
      both patients. This case illustrates the significant phenotypic variability of
      acrodysostosis even within one family with identical mutations. Hence, a specific
      clinical diagnosis of acrodysostosis remains challenging because of great
      interindividual variability and a substantial overlap of the two subtypes as well
      as with other related Gsalpha-cAMP-signalling-linked disorders.

PMID- 28515033
TI  - Acanthocytosis and HyperCKemia

PMID- 28515035
TI  - Ray Dolan: Blues on the brain.

PMID- 28515034
TI  - Wrist Circumference and Frame Size Percentiles in 6-17-Year-Old Turkish Children
      and Adolescents in Kayseri.
AB  - OBJECTIVE: The aim of the current study was to provide wrist circumference (WrC)
      and body frame size (height/WrC) percentile values in Turkish children and
      adolescents aged 6-17 years. METHODS: In this cross-sectional study, the data of
      "Determination of Anthropometric Measures of Turkish Children and Adolescents"
      (DAMTCA II) study in Kayseri/Turkey were used. A total of 4330 observations were
      recorded (1931 boys, 2399 girls). The WrC and frame size reference values were
      produced with generalized additive models for location, scale and shape. RESULTS:
      The WrC percentiles (3rd-97th) were calculated. The frame size (height/WrC) was
      estimated as small, medium, and large (<15th, 15-85th, and >=85th percentiles,
      respectively). For both genders, WrC linearly increased with age (13.0-16.8 cm
      for boys and 12.5-15.5 cm for girls). In boys and girls, the mean +/- standard
      deviation of WrC is 13.00+/-0.89 cm and 12.48+/-0.93 cm (6 years) and increases
      to 16.83+/-1.16 and 15.58+/-0.86 cm (17 years), respectively. The WrC values in
      all age groups were higher in boys compared with girls. The increment in frame
      size from 6 to 17 years were 1.25 cm in boys and 0.85 cm in girls. CONCLUSION:
      WrC is a simple, easy-to-detect anthropometric index which is not subject to
      measurement errors. Additionally, WrC can be used both to decide about frame size
      and to determine metabolic risks related to obesity. We consider that this easy
      to-get anthropometric index can be used both in screening procedures and clinical
      assessment procedure for obesity-related metabolic consequences.

PMID- 28515038
TI  - Simon Stevens uses art to sidestep purdah.

PMID- 28515037
TI  - Labour's pledge to boost NHS funding by L30bn is "still not enough".

PMID- 28515040
TI  - A systematic review of overlapping microRNA patterns in systemic sclerosis and
      idiopathic pulmonary fibrosis.
AB  - Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary
      fibrosis, two disorders where lung involvement carries a poor prognosis. Although
      much has been learned about the pathogenesis of these conditions, interventions
      capable of reversing or, at the very least, halting disease progression are not
      available. Recent studies point to the potential role of micro messenger RNAs
      (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA
      sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and
      encoded in the genome. By acting on several genes, microRNAs control protein
      expression. Considering the above, we engaged in a systematic review of the
      literature in search of overlapping observations implicating microRNAs in the
      pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis
      (SSc). Our objective was to uncover top microRNA candidates for further
      investigation based on their mechanisms of action and their potential for serving
      as targets for intervention against lung fibrosis. Our review points to microRNAs
      of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct
      and counter-balancing actions related to lung fibrosis. Based on this, we
      speculate that readjusting the disrupted balance between these microRNAs in lung
      fibrosis related to SSc and IPF may have therapeutic potential.

PMID- 28515041
TI  - Multidisciplinary evaluation of interstitial lung diseases: current insights:
      Number 1 in the Series "Radiology" Edited by Nicola Sverzellati and Sujal Desai.
AB  - Multidisciplinary team (MDT) diagnosis is regarded as the diagnostic reference
      standard for interstitial lung disease (ILD). Several studies have reported that
      MDT diagnosis is associated with higher levels of diagnostic confidence and
      better interobserver agreement when compared to the individual components of the
      MDT in isolation. Although this recommendation is widely accepted, no guideline
      statement specifies what constitutes an MDT meeting and how its participants
      should govern it. Furthermore, the precise role of an MDT meeting in the setting
      of ILD may vary from one group to another. For example, in some cases, the
      meeting will confine its discussion to characterising the disease and formulating
      diagnosis. In others, management decisions may also be part of the discussion.
      Surprisingly, there is no consensus on how MDT diagnosis is validated. As
      multidisciplinary evaluation contains all the available clinical information on
      an individual patient, there is no reference standard against which the veracity
      of MDT diagnosis can be tested. Finally, many of these uncertainties surrounding
      MDT meeting practice are unlikely to be answered by traditional evidence-based
      studies, which create difficulties when generating guideline recommendations.
      There is clearly a need for expert consensus on what constitutes acceptable MDT
      meeting practice. This consensus will need to be flexible to accommodate the
      variability in resources available to fledgling MDT groups and the variable
      nature of patients requiring discussion.

PMID- 28515042
TI  - Radiology in diffuse parenchymal lung disease and lung nodules.

PMID- 28515045
TI  - Private sector should have same safety rigour as NHS, say surgeons after Paterson
      conviction.

PMID- 28515044
TI  - Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A
      Network Mendelian Randomization Study.
AB  - RATIONALE: Observational studies have found shorter leukocyte telomere length
      (TL) to be a risk factor for coronary heart disease (CHD), and recently the
      association was suggested to be causal. However, the relationship between TL and
      common metabolic risk factors for CHD is not well understood. Whether these risk
      factors could explain pathways from TL to CHD warrants further attention.
      OBJECTIVE: To examine whether metabolic risk factors for CHD mediate the causal
      pathway from short TL to increased risk of CHD using a network Mendelian
      randomization design. METHODS AND RESULTS: Summary statistics from several genome
      wide association studies were used in a 2-sample Mendelian randomization study
      design. Network Mendelian randomization analysis-an approach using genetic
      variants as the instrumental variables for both the exposure and mediator to
      infer causality-was performed to examine the causal association between telomeres
      and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere
      Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D
      Consortium data were used (case=22 233 and control=64 762) for CHD, and other
      consortia data were used for metabolic traits (fasting insulin, triglyceride,
      total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes
      mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip
      ratio). One-unit increase of genetically determined TL was associated with -0.07
      (95% confidence interval, -0.01 to -0.12; P=0.01) lower log-transformed fasting
      insulin (pmol/L) and 21% lower odds (95% confidence interval, 3-35; P=0.02) of
      CHD. Higher genetically determined log-transformed fasting insulin level was
      associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01
      3.41; P=0.04). CONCLUSIONS: Overall, our findings support a role of insulin as a
      mediator on the causal pathway from shorter telomeres to CHD pathogenesis.

PMID- 28515043
TI  - Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of
      Alzheimer Abeta Peptides.
AB  - RATIONALE: Increasing evidence indicates that alterations of the cerebral
      microcirculation may play a role in Alzheimer disease, the leading cause of late
      life dementia. The amyloid-beta peptide (Abeta), a key pathogenic factor in
      Alzheimer disease, induces profound alterations in neurovascular regulation
      through the innate immunity receptor CD36 (cluster of differentiation 36), which,
      in turn, activates a Nox2-containing NADPH oxidase, leading to cerebrovascular
      oxidative stress. Brain perivascular macrophages (PVM) located in the
      perivascular space, a major site of brain Abeta collection and clearance, are
      juxtaposed to the wall of intracerebral resistance vessels and are a powerful
      source of reactive oxygen species. OBJECTIVE: We tested the hypothesis that PVM
      are the main source of reactive oxygen species responsible for the
      cerebrovascular actions of Abeta and that CD36 and Nox2 in PVM are the molecular
      substrates of the effect. METHODS AND RESULTS: Selective depletion of PVM using
      intracerebroventricular injection of clodronate abrogates the reactive oxygen
      species production and cerebrovascular dysfunction induced by Abeta applied
      directly to the cerebral cortex, administered intravascularly, or overproduced in
      the brain of transgenic mice expressing mutated forms of the amyloid precursor
      protein (Tg2576 mice). In addition, using bone marrow chimeras, we demonstrate
      that PVM are the cells expressing CD36 and Nox2 responsible for the dysfunction.
      Thus, deletion of CD36 or Nox2 from PVM abrogates the deleterious vascular
      effects of Abeta, whereas wild-type PVM reconstitute the vascular dysfunction in
      CD36-null mice. CONCLUSIONS: The data identify PVM as a previously unrecognized
      effector of the damaging neurovascular actions of Abeta and unveil a new
      mechanism by which brain-resident innate immune cells and their receptors may
      contribute to the pathobiology of Alzheimer disease.

PMID- 28515046
TI  - KIF1B and NF1 are the most frequently mutated genes in paraganglioma and
      pheochromocytoma tumors.

PMID- 28515048
TI  - Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During
      Rapid Syncytial Cell Cycles in Drosophila.
AB  - Many metabolic enzymes are evolutionarily highly conserved and serve a central
      function in the catabolism and anabolism of cells. The serine hydroxymethyl
      transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa
      feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We identified a
      Drosophila mutation in SHMT (CG3011) in a screen for blastoderm mutants. Embryos
      from SHMT mutant germline clones specifically arrest the cell cycle in interphase
      13 at the time of the midblastula transition (MBT) and prior to cellularization.
      The phenotype is due to a loss of enzymatic activity as it cannot be rescued by
      an allele with a point mutation in the catalytic center but by an allele based on
      the SHMT coding sequence from Escherichia coli The onset of zygotic gene
      expression and degradation of maternal RNAs in SHMT mutant embryos are largely
      similar to that in wild-type embryos. The specific timing of the defects in SHMT
      mutants indicates that at least one of the SHMT-dependent metabolites becomes
      limiting in interphase 13, if it is not produced by the embryo. Our data suggest
      that mutant eggs contain maternally-provided and SHMT-dependent metabolites in
      amounts that suffice for early development until interphase 13.

PMID- 28515050
TI  - The Mapping of Predicted Triplex DNA:RNA in the Drosophila Genome Reveals a
      Prominent Location in Development- and Morphogenesis-Related Genes.
AB  - Double-stranded DNA is able to form triple-helical structures by accommodating a
      third nucleotide strand. A nucleic acid triplex occurs according to Hoogsteen
      rules that predict the stability and affinity of the third strand bound to the
      Watson-Crick duplex. The "triplex-forming oligonucleotide" (TFO) can be a short
      sequence of RNA that binds to the major groove of the targeted duplex only when
      this duplex presents a sequence of purine or pyrimidine bases in one of the DNA
      strands. Many nuclear proteins are known to bind triplex DNA or DNA:RNA, but
      their biological functions are unexplored. We identified sequences that are
      capable of engaging as the "triplex-forming oligonucleotide" in both the pre
      lncRNA and pre-mRNA collections of Drosophila melanogaster These motifs were
      matched against the Drosophila genome in order to identify putative sequences of
      triplex formation in intergenic regions, promoters, and introns/exons. Most of
      the identified TFOs appear to be located in the intronic region of the analyzed
      genes. Computational prediction of the most targeted genes by TFOs originating
      from pre-lncRNAs and pre-mRNAs revealed that they are restrictively associated
      with development- and morphogenesis-related gene networks. The refined analysis
      by Gene Ontology enrichment demonstrates that some individual TFOs present genome
      wide scale matches that are located in numerous genes and regulatory sequences.
      The triplex DNA:RNA computational mapping at the genome-wide scale suggests broad
      interference in the regulatory process of the gene networks orchestrated by TFO
      RNAs acting in association simultaneously at multiple sites.

PMID- 28515051
TI  - Understanding and supporting women with polycystic ovary syndrome: a qualitative
      study in an ethnically diverse UK sample.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a lifelong condition. Its symptoms
      have been linked with psychological consequences, but less attention has been
      given to the daily implications of living with PCOS. We aimed to explore women's
      experiences living with PCOS, and the potential acceptability of group education
      sessions for this target group. METHODS: Women with PCOS were recruited from an
      ethnically diverse UK community. Twelve semi-structured interviews were
      conducted. Analysis was underpinned by the constant comparative approach and
      involved the identification and exploration of key themes. RESULTS: Participants
      reported a range of symptoms linked with PCOS, including problems relating to
      menstruation and weight difficulties. Hirsutism was reported as the most
      distressing symptom. Emergent themes included perceptions about symptoms and
      delays in receiving a diagnosis; psychological distress; practical implications
      of living with the condition; coping with PCOS and perceived support needs. Some
      findings were specific to cultural backgrounds. Participants were supportive of
      the idea of group education for women with PCOS and suggested a need to provide
      education within the community and health care providers. DISCUSSION: Women with
      PCOS experience high psychological distress and difficulties with coping with
      their condition. Suggested strategies to reduce the negative psychological impact
      include education at various levels.

PMID- 28515049
TI  - A Generalized Linear Model for Decomposing Cis-regulatory, Parent-of-Origin, and
      Maternal Effects on Allele-Specific Gene Expression.
AB  - Joint quantification of genetic and epigenetic effects on gene expression is
      important for understanding the establishment of complex gene regulation systems
      in living organisms. In particular, genomic imprinting and maternal effects play
      important roles in the developmental process of mammals and flowering plants.
      However, the influence of these effects on gene expression are difficult to
      quantify because they act simultaneously with cis-regulatory mutations. Here we
      propose a simple method to decompose cis-regulatory (i.e., allelic genotype),
      genomic imprinting [i.e., parent-of-origin (PO)], and maternal [i.e., maternal
      genotype (MG)] effects on allele-specific gene expression using RNA-seq data
      obtained from reciprocal crosses. We evaluated the efficiency of method using a
      simulated dataset and applied the method to whole-body Drosophila and mouse
      trophoblast stem cell (TSC) and liver RNA-seq data. Consistent with previous
      studies, we found little evidence of PO and MG effects in adult Drosophila
      samples. In contrast, we identified dozens and hundreds of mouse genes with
      significant PO and MG effects, respectively. Interestingly, a similar number of
      genes with significant PO effect were detect in mouse TSCs and livers, whereas
      more genes with significant MG effect were observed in livers. Further
      application of this method will clarify how these three effects influence gene
      expression levels in different tissues and developmental stages, and provide
      novel insight into the evolution of gene expression regulation.

PMID- 28515047
TI  - Centrosome amplification: a suspect in breast cancer and racial disparities.
AB  - The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is
      coming into focus following years of meticulous experimentation, which have
      elucidated the powerful abilities of CA to promote cellular invasion, disrupt
      stem cell division, drive chromosomal instability (CIN) and perturb tissue
      architecture, activities that can accelerate tumor progression. Integration of
      the extant in vitro, in vivo and clinical data suggests that in some tissues CA
      may be a tumor-initiating event, in others a consequential 'hit' in multistep
      tumorigenesis, and in some others, non-tumorigenic. However, in vivo data are
      limited and primarily focus on PLK4 (which has CA-independent mechanisms by which
      it promotes aggressive cellular phenotypes). In vitro breast cancer models
      suggest that CA can promote tumorigenesis in breast cancer cells in the setting
      of p53 loss or mutation, which can both trigger CA and promote cellular tolerance
      to its tendency to slow proliferation and induce aneuploidy. It is thus our
      perspective that CA is likely an early hit in multistep breast tumorigenesis that
      may sometimes be lost to preserve aggressive karyotypes acquired through
      centrosome clustering-mediated CIN, both numerical and structural. We also
      envision that the robust link between p53 and CA may underlie, to a considerable
      degree, racial health disparity in breast cancer outcomes. This question is
      clinically significant because, if it is true, then analysis of centrosomal
      profiles and administration of centrosome declustering drugs could prove highly
      efficacious in risk stratifying breast cancers and treating African American (AA)
      women with breast cancer.

PMID- 28515052
TI  - Exercise training improves free testosterone in lifelong sedentary aging men.
AB  - As the impact of high-intensity interval training (HIIT) on systemic hormones in
      aging men is unstudied to date, we investigated whether total testosterone (TT),
      sex hormone-binding globulin (SHBG), free testosterone (free-T) and cortisol (all
      in serum) were altered following HIIT in a cohort of 22 lifelong sedentary (62 +/
      2 years) older men. As HIIT requires preconditioning exercise in sedentary
      cohorts, participants were tested at three phases, each separated by six-week
      training; baseline (phase A), following conditioning exercise (phase B) and post
      HIIT (phase C). Each measurement phase used identical methods. TT was
      significantly increased following HIIT (~17%; P < 0.001) with most increase
      occurring during preconditioning (~10%; P = 0.007). Free-T was unaffected by
      conditioning exercise (P = 0.102) but was significantly higher following HIIT
      compared to baseline (~4.5%; P = 0.023). Cortisol remained unchanged from A to C
      (P = 0.138). The present data indicate a combination of preconditioning, and HIIT
      increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting
      for a small but statistically significant increase in free-T. Further study is
      required to determine the biological importance of small improvements in free-T
      in aging men.

PMID- 28515053
TI  - Berberine reduced blood pressure and improved vasodilation in diabetic rats.
AB  - Hyperglycemia and hypertension are considered to be the two leading risk factors
      for vascular disease in diabetic patients. However, few pharmacologic agents
      could provide a combinational therapy for controlling hyperglycemia and
      hypertension at the same time in diabetes. The objectives of this study are to
      investigate whether berberine treatment could directly reduce blood pressure and
      identify the molecular mechanism underlying the vascular protection of berberine
      in diabetic rats. Berberine was intragastrically administered with different
      dosages of 50, 100 and 200 mg/kg/day to diabetic rats for 8 weeks since the
      injection of streptozotocin. The endothelium-dependent/-independent relaxation in
      middle cerebral arteries was investigated. The activity of large-conductance Ca2+
      activated K+ channel (BKCa) was investigated by recording whole-cell currents,
      analyzing single-channel activities and assessing the expressions of alpha- and
      beta1-subunit at protein or mRNA levels. Results of the study suggest that
      chronic administration of 100 mg/kg/day berberine not only lowered blood glucose
      but also reduced blood pressure and improved vasodilation in diabetic rats.
      Furthermore, berberine markedly increased the function and expression of BKCa
      beta1-subunit in cerebral vascular smooth muscle cells (VSMCs) isolated from
      diabetic rats or when exposed to hyperglycemia condition. The present study
      provided initial evidences that berberine reduced blood pressure and improved
      vasodilation in diabetic rats by activation of BKCa channel in VSMCs, which
      suggested that berberine might provide a combinational therapy for controlling
      hyperglycemia and blood pressure in diabetes. Furthermore, our work indicated
      that activation of BKCa channel might be the underlying mechanism responsible for
      the vascular protection of berberine in diabetes.

PMID- 28515054
TI  - Longitudinal decline in lung function among older construction workers.
AB  - BACKGROUND: Occupational exposures to vapours, gasses, dusts and fumes (VGDF) and
      chest X-ray abnormalities by the International Labour Office (ILO) classification
      system are associated with reduced lung function, with the majority of published
      studies being cross-sectional. We examined the effects of VGDF exposures, as well
      as ILO parenchymal changes, pleural plaque and diffuse pleural thickening (DPT)
      on reduction in lung function in a longitudinal study. METHODS: Chest radiographs
      and spirometry for 3150 ageing construction workers enrolled in a medical
      screening programme with a baseline and at least one follow-up examination were
      studied. Indices for VGDF exposure, parenchymal changes, pleural plaque and DPT
      severity were developed and used in longitudinal mixed models of lung function.
      RESULTS: Smoking and VGDF exposure were associated with decreased FEV1 and FVC at
      baseline as well as accelerated rates of annual decline. High VGDF exposure was
      associated with a yearly decline of -19.5 mL for FEV1 and -15.7 mL for FVC.
      Parenchymal abnormalities, pleural plaque and DPT were more strongly associated
      with reduced FVC. An increase of one unit in the pleural plaque severity index
      resulted in approximately -5.3 mL loss of FVC and -3.3 mL loss of FEV1, with a
      possible non-linear effect of plaque on FEV1. CONCLUSIONS: Increasing pleural
      plaque severity was associated with progressively greater loss of FVC and FEV1,
      supporting a causal association. VGDF exposures were associated with reduced FVC
      and FEV1 at baseline as well as accelerated annual loss of lung function.

PMID- 28515056
TI  - Reducing musculoskeletal injury and concussion risk in schoolboy rugby players
      with a pre-activity movement control exercise programme: a cluster randomised
      controlled trial.
AB  - BACKGROUND: Injury risk in youth rugby has received much attention, highlighting
      the importance of establishing evidence-based injury reduction strategies. AIM:
      To determine the efficacy of a movement control exercise programme in reducing
      injuries in youth rugby players and to investigate the effect of programme dose
      on injury measures. METHODS: In a cluster-randomised controlled trial, 40
      independent schools (118 teams, 3188 players aged 14-18 years) were allocated to
      receive either the intervention or a reference programme, both of which were to
      be delivered by school coaches. The intervention comprised balance training,
      whole-body resistance training, plyometric training, and controlled rehearsal of
      landing and cutting manoeuvres. Time-loss (>24 hours) injuries arising from
      school rugby matches were recorded by coaches and medical staff. RESULTS: 441
      time-loss match injuries (intervention, 233; control, 208) were reported across
      15 938 match exposure-hours (intervention, 9083; control, 6855). Intention-to
      treat results indicated unclear effects of trial arm on overall match injury
      incidence (rate ratio (RR)=0.85, 90% confidence limits 0.61 to 1.17), although
      clear reductions were evident in the intervention arm for concussion incidence
      (RR=0.71, 0.48 to 1.05). When trial arm comparisons were limited to teams who had
      completed three or more weekly programme sessions on average, clear reductions in
      overall match injury incidence (RR=0.28, 0.14 to 0.51) and concussion incidence
      (RR=0.41, 0.17 to 0.99) were noted in the intervention group. CONCLUSION: A
      preventive movement control exercise programme can reduce match injury outcomes,
      including concussion, in schoolboy rugby players when compared with a
      standardised control exercise programme, although to realise the greatest effects
      players should complete the programme at least three times per week.

PMID- 28515058
TI  - Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44 avidin
      binding technique for the repairing of cartilage defects in the weight-bearing
      area of knee joints in pigs.
AB  - OBJECTIVES: The lack of effective treatment for cartilage defects has prompted
      investigations using tissue engineering techniques for their regeneration and
      repair. The success of tissue-engineered repair of cartilage may depend on the
      rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this
      study was to repair full-thickness defects in articular cartilage in the weight
      bearing area of a porcine model, and to investigate whether the CD44 monoclonal
      antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue
      engineered cartilage. METHODS: Cartilage defects were created in the load-bearing
      region of the lateral femoral condyle of mini-type pigs. The defects were
      repaired with traditional tissue-engineered cartilage, tissue-engineered
      cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered
      cartilage constructed with the CBA technique and with autologous cartilage. The
      biomechanical properties, Western blot assay, histological findings and
      immunohistochemical staining were explored. RESULTS: The CBA group showed similar
      results to the autologous group in biomechanical properties, Moran's criteria,
      histological tests and Wakitani histological scoring. CONCLUSIONS: These results
      suggest that tissue-engineered cartilage constructed using the CBA technique
      could be used effectively to repair cartilage defects in the weight-bearing area
      of joints.Cite this article: H. Lin, J. Zhou, L. Cao, H. R. Wang, J. Dong, Z. R.
      Chen. Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44
      avidin binding technique for the repairing of cartilage defects in the weight
      bearing area of knee joints in pigs. Bone Joint Res 2017;6:-295. DOI:
      10.1302/2046-3758.65.BJR-2016-0277.

PMID- 28515057
TI  - Delaying ACL reconstruction and treating with exercise therapy alone may alter
      prognostic factors for 5-year outcome: an exploratory analysis of the KANON
      trial.
AB  - AIM: Identify injury-related, patient-reported and treatment-related prognostic
      factors for 5-year outcomes in acutely ACL-ruptured individuals managed with
      early reconstruction plus exercise therapy, exercise therapy plus delayed
      reconstruction or exercise therapy alone. METHODS: Exploratory analysis of the
      Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON)
      trial (ISRCTN84752559). Relationships between prognostic factors (baseline
      cartilage, meniscus and osteochondral damage, baseline extension deficit,
      baseline patient-reported outcomes, number of rehabilitation visits,
      graft/contralateral ACL rupture, non-ACL surgery and ACL treatment strategy) and
      5-year Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms,
      sport/recreation and quality of life (QOL) scores were explored using
      multivariable linear regression. Estimates were adjusted for sex, age, body mass
      index, preinjury activity level, education and smoking. RESULTS: For all
      participants (n=118), graft/contralateral ACL rupture, non-ACL surgery and worse
      baseline 36-item Short-Form Mental Component Scores were associated with worse
      outcomes. Treatment with exercise therapy alone was a prognostic factor for less
      knee symptoms compared with early reconstruction plus exercise therapy
      (regression coefficient 10.1, 95% CI 2.3 to 17.9). Baseline meniscus lesion was
      associated with worse sport/recreation function (-14.4, 95% CI -27.6 to -1.3) and
      osteochondral lesions were associated with worse QOL (-12.3, 95% CI -24.3 to 
      0.4) following early reconstruction plus exercise therapy. In the same group,
      undergoing additional non-ACL surgery and worse baseline KOOS scores were
      prognostic for worse outcome on all KOOS subscales. Following delayed
      reconstruction, baseline meniscus damage was a prognostic factor for less pain
      (14.3, 95% CI 0.7 to 27.9). Following exercise therapy alone, undergoing non-ACL
      surgery was prognostic for worse pain. CONCLUSIONS: Treatment-dependent
      differences in prognostic factors for 5-year outcomes may support individualised
      treatment after acute ACL rupture in young active individuals. TRIAL REGISTRATION
      NUMBER: Current Controlled Trials ISRCTN84752559.

PMID- 28515055
TI  - Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF
      Mutations.
AB  - African-American men have the highest incidence of and mortality from prostate
      cancer. Whether a biological basis exists for this disparity remains unclear.
      Exome sequencing (n = 102) and targeted validation (n = 90) of localized primary
      hormone-naive prostate cancer in African-American men identified several gene
      mutations not previously observed in this context, including recurrent loss-of
      function mutations in ERF, an ETS transcriptional repressor, in 5% of cases.
      Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of
      primary prostate cancers and mutations or deletions in ERF in 3% to 5% of lethal
      castration-resistant prostate cancers. Knockdown of ERF confers increased
      anchorage-independent growth and generates a gene expression signature associated
      with oncogenic ETS activation and androgen signaling. Together, these results
      suggest that ERF is a prostate cancer tumor-suppressor gene. More generally, our
      findings support the application of systematic cancer genomic characterization in
      settings of broader ancestral diversity to enhance discovery and, eventually,
      therapeutic applications.Significance: Systematic genomic sequencing of prostate
      cancer in African-American men revealed new insights into prostate cancer,
      including the identification of ERF as a prostate cancer gene; somatic copy
      number alteration differences; and uncommon PIK3CA and PTEN alterations. This
      study highlights the importance of inclusion of underrepresented minorities in
      cancer sequencing studies. Cancer Discov; 7(9); 973-83. (c)2017 AACR.This article
      is highlighted in the In This Issue feature, p. 920.

PMID- 28515059
TI  - Antibiotic stability over six weeks in aqueous solution at body temperature with
      and without heat treatment that mimics the curing of bone cement.
AB  - OBJECTIVES: Thermal stability is a key property in determining the suitability of
      an antibiotic agent for local application in the treatment of orthopaedic
      infections. Despite the fact that long-term therapy is a stated goal of novel
      local delivery carriers, data describing thermal stability over a long period are
      scarce, and studies that avoid interference from specific carrier materials are
      absent from the orthopaedic literature. METHODS: In this study, a total of 38
      frequently used antibiotic agents were maintained at 37 degrees C in saline
      solution, and degradation and antibacterial activity assessed over six weeks. The
      impact of an initial supplementary heat exposure mimicking exothermically curing
      bone cement was also tested as this material is commonly used as a local delivery
      vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to
      mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity
      over time was determined by the Kirby-Bauer disk diffusion assay. RESULTS: The
      heat exposure mimicking curing bone cement had minimal effect on stability for
      most antibiotics, except for gentamicin which experienced approximately 25%
      degradation as measured by immunoassay. Beta-lactam antibiotics were found to
      degrade quite rapidly at 37 degrees C regardless of whether there was an initial
      heat exposure. Excellent long-term stability was observed for aminoglycosides,
      glycopeptides, tetracyclines and quinolones under both conditions. CONCLUSIONS:
      This study provides a valuable dataset for orthopaedic surgeons considering local
      application of antibiotics, and for material scientists looking to develop next
      generation controlled or extended-release antibiotic carriers.Cite this article:
      E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl.
      Antibiotic stability over six weeks in aqueous solution at body temperature with
      and without heat treatment that mimics the curing of bone cement. Bone Joint J
      2017;6:296-306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1.

PMID- 28515061
TI  - Is there a better way to set population iron recommendations?

PMID- 28515060
TI  - Barriers and facilitators experienced in collaborative prospective research in
      orthopaedic oncology: A qualitative study.
AB  - OBJECTIVES: As tumours of bone and soft tissue are rare, multicentre prospective
      collaboration is essential for meaningful research and evidence-based advances in
      patient care. The aim of this study was to identify barriers and facilitators
      encountered in large-scale collaborative research by orthopaedic oncological
      surgeons involved or interested in prospective multicentre collaboration.
      METHODS: All surgeons who were involved, or had expressed an interest, in the
      ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were
      invited to participate in a focus group to discuss their experiences with
      collaborative research in this area. The discussion was digitally recorded,
      transcribed and anonymised. The transcript was analysed qualitatively, using an
      analytic approach which aims to organise the data in the language of the
      participants with little theoretical interpretation. RESULTS: The 13 surgeons who
      participated in the discussion represented orthopaedic oncology practices from
      seven countries (Argentina, Brazil, Italy, Spain, Denmark, United States and
      Canada). Four categories and associated themes emerged from the discussion: the
      need for collaboration in the field of orthopaedic oncology due to the rarity of
      the tumours and the need for high level evidence to guide treatment; motivational
      factors for participating in collaborative research including establishing proof
      of principle, learning opportunity, answering a relevant research question and
      being part of a collaborative research community; barriers to participation
      including funding, personal barriers, institutional barriers, trial barriers, and
      administrative barriers and facilitators for participation including
      institutional facilitators, leadership, authorship, trial set-up, and the support
      of centralised study coordination. CONCLUSIONS: Orthopaedic surgeons involved in
      an ongoing international randomised controlled trial (RCT) were motivated by many
      factors to participate. There were a number of barriers to and facilitators for
      their participation. There was a collective sense of fatigue experienced in
      overcoming these barriers, which was mirrored by a strong collective sense of the
      importance of, and need for, collaborative research in this field. The
      experiences were described as essential educational first steps to advance
      collaborative studies in this area. Knowledge gained from this study will inform
      the development of future large-scale collaborative research projects in
      orthopaedic oncology.Cite this article: J. S. Rendon, M. Swinton, N. Bernthal, M.
      Boffano, T. Damron, N. Evaniew, P. Ferguson, M. Galli Serra, W. Hettwer, P.
      McKay, B. Miller, L. Nystrom, W. Parizzia, P. Schneider, A. Spiguel, R. Velez, K.
      Weiss, J. P. Zumarraga, M. Ghert. Barriers and facilitators experienced in
      collaborative prospective research in orthopaedic oncology: A qualitative study.
      Bone Joint Res 2017;6:-314. DOI: 10.1302/2046-3758.65.BJR-2016-0192.R1.

PMID- 28515062
TI  - Changes in total energy intake and macronutrient composition after bariatric
      surgery predict long-term weight outcome: findings from the Swedish Obese
      Subjects (SOS) study.
AB  - Background: Approximately 20-30% of obese patients do not achieve successful
      weight outcomes after bariatric surgery.Objective: We examined whether short-term
      changes (<=0.5 y postsurgery) in energy intake and macronutrient composition
      after bariatric surgery could predict 10-y weight change.Design: Participants
      were recruited from the Swedish Obese Subjects (SOS) study, which was a matched
      (nonrandomized) prospective trial that compared bariatric surgery with usual care
      for obese patients. A total of 2010 patients who underwent bariatric surgery were
      included in the study. Physical examinations (e.g., weight) and questionnaires
      (e.g., dietary questionnaire) were completed before and 0.5, 1, 2, 3, 4, 6, 8,
      and 10 y after surgery. For the main analytic strategy, a linear mixed model was
      implemented, which included repeated measures with a random intercept and an
      unstructured covariance matrix.Results: Short-term changes in energy intake (P <
      0.001) and in relative proportions of energy from carbohydrates (P < 0.001), fat
      (P < 0.001), and protein (P < 0.05) were associated with 10-y weight change after
      bariatric surgery. At the 10-y follow-up, men and women with the largest
      reductions in energy intake had lost 7.3% and 3.9% more weight, respectively,
      compared with that of subjects with the smallest intake reductions (P < 0.001).
      Greater weight loss was achieved in men and women who favored protein and
      carbohydrates over fat and in subjects who favored protein over carbohydrates
      than in individuals who favored the opposite changes in macronutrient composition
      (P < 0.05).Conclusions: The level of energy restriction that is achieved at 0.5 y
      after bariatric surgery predicts long-term weight loss. Weight loss is also
      associated with a changing dietary macronutrient composition. This trial was
      registered at clinicaltrials.gov as NCT01479452.

PMID- 28515063
TI  - Learning to like vegetables during breastfeeding: a randomized clinical trial of
      lactating mothers and infants.
AB  - Background: What lactating mothers eat flavors breast milk and, in turn, modifies
      their infants' acceptance of similarly flavored foods.Objective: We sought to
      determine the effects of the timing and duration of eating a variety of
      vegetables during breastfeeding on the liking of vegetables in both members of
      the dyad.Design: We conducted a randomized controlled study of 97 mother-infant
      dyads. Lactating mothers drank vegetable, beet, celery, and carrot juices for 1
      mo beginning at 0.5, 1.5, or 2.5 mo postpartum or for 3 mo beginning at 0.5 mo
      postpartum. The control group drank equal volumes of water and avoided drinking
      the juices. Mothers rated the tastes of the juices and self-reported dietary
      intakes at each monthly visit (0.5-4.5 mo). After weaning, when 7.9 mo of age,
      infants' acceptance of plain, carrot-flavor (exposed flavor), and broccoli-flavor
      (nonexposed flavor) cereals was assessed on separate days.Results: The timing of
      exposure affected the acceptance of the carrot flavor that did not generalize to
      the novel broccoli flavor. A relatively brief experience (1 mo) with vegetable
      flavors in mothers' milk, starting at 0.5 mo postpartum, was sufficient to shift
      the hedonic tone, which resulted in a faster rate of eating carrot-flavored
      cereal than that in infants who were exposed during subsequent months or not at
      all. One month of exposure had a greater effect than 3 mo of exposure or no
      exposure. Regardless of when exposure occurred, infants were less likely to
      display facial expressions of distaste initially when eating the carrot cereal.
      Over time, mothers liked the tastes of carrot, beet, and celery juices more, but
      no changes in dietary intake of vegetables were observed.Conclusions: Early life
      may be an optimum time for both infants and their mothers to learn to like the
      taste of healthy foods. More research is needed to facilitate the liking and
      eating of these foods by mothers, which will, in turn, increase the likelihood of
      their feeding these foods to their children. This trial was registered at
      clinicaltrials.gov as NCT01667549.

PMID- 28515065
TI  - Neonatal vitamin D status from archived dried blood spots and future risk of
      fractures in childhood: results from the D-tect study, a population-based case
      cohort study.
AB  - Background: Whether antenatal and neonatal vitamin D status have clinical
      relevance in fracture prevention has not been examined extensively, although
      observational studies indicate that fetal life may be a sensitive period in
      relation to bone growth and mineralization during childhood.Objective: We
      examined whether 25-hydroxyvitamin D3 [25(OH)D3] concentrations in stored
      neonatal dried blood spot (DBS) samples are associated with pediatric fracture
      risk. We hypothesized that in particular, low neonatal vitamin D status may be a
      risk factor for fracture incidence among children.Design: In a register-based
      case-cohort study design, the case group was composed of 1039 individuals who
      were randomly selected from a total of 82,154 individuals who were born during
      1989-1999 and admitted to a Danish hospital with a fracture of the forearm,
      wrist, scaphoid bone, clavicle, or ankle at age 6-13 y. The subcohort was
      composed of 1600 individuals randomly selected from all Danish children born
      during 1989-1999. The neonatal 25(OH)D3 concentrations in DBS samples were
      assessed by using highly sensitive chromatography-tandem mass
      spectrometry.Results: The mean +/- SD 25(OH)D3 concentration for all subjects was
      27.7 +/- 18.9 nmol/L [median (IQR): 23.5 nmol/L (13.3, 37.3 nmol/L)] and showed
      significant monthly variation (P < 0.0001) with the highest values in July and
      August. Individuals in the middle quintile of neonatal 25(OH)D3 had lower odds of
      sustaining a fracture than did those in the lowest quintile (adjusted OR: 0.75;
      95% CI: 0.58, 0.96), but a global test did not show any significant overall
      association (adjusted P = 0.13).Conclusions: This study suggested that neonatal
      vitamin D status does not influence subsequent fracture risk in childhood. This
      is in accordance with studies that report no association between antenatal
      maternal vitamin D status and childhood fractures. Further studies are needed to
      examine fracture risk in relation to prenatal vitamin D status in a randomized
      controlled setting.

PMID- 28515066
TI  - Estimating salt intake in humans: not so easy!

PMID- 28515064
TI  - Genetics of serum carotenoid concentrations and their correlation with obesity
      related traits in Mexican American children.
AB  - Background: Dietary intake of phytonutrients present in fruits and vegetables,
      such as carotenoids, is associated with a lower risk of obesity and related
      traits, but the impact of genetic variation on these associations is poorly
      understood, especially in children.Objective: We estimated common genetic
      influences on serum carotenoid concentrations and obesity-related traits in
      Mexican American (MA) children.Design: Obesity-related data were obtained from
      670 nondiabetic MA children, aged 6-17 y. Serum alpha- and beta-carotenoid
      concentrations were measured in ~570 (alpha-carotene in 565 and beta-carotene in
      572) of these children with the use of an ultraperformance liquid chromatography
      photodiode array. We determined heritabilities for both carotenoids and examined
      their genetic relation with 10 obesity-related traits [body mass index (BMI),
      waist circumference (WC), high-density lipoprotein (HDL) cholesterol,
      triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting
      insulin and glucose, and homeostasis model assessment of insulin resistance] by
      using family data and a variance components approach. For these analyses,
      carotenoid values were inverse normalized, and all traits were adjusted for
      significant covariate effects of age and sex.Results: Carotenoid concentrations
      were highly heritable and significant [alpha-carotene: heritability (h2) = 0.81,
      P = 6.7 * 10-11; beta-carotene: h2 = 0.90, P = 3.5 * 10-15]. After adjusting for
      multiple comparisons, we found significant (P <= 0.05) negative phenotypic
      correlations between carotenoid concentrations and the following traits: BMI, WC,
      FM, and triglycerides (range: alpha-carotene = -0.19 to -0.12; beta-carotene = 
      0.24 to -0.13) and positive correlations with HDL cholesterol (alpha-carotene =
      0.17; beta-carotene = 0.24). However, when the phenotypic correlations were
      partitioned into genetic and environmental correlations, we found marginally
      significant (P = 0.051) genetic correlations only between beta-carotene and BMI (
      0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple
      comparisons. None of the environmental correlations were significant.Conclusions:
      The findings from this study suggest that the serum carotenoid concentrations
      were under strong additive genetic influences based on variance components
      analyses, and that the common genetic factors may influence beta-carotene and
      obesity and lipid traits in MA children.

PMID- 28515067
TI  - Relative contribution of alpha-carotene to postprandial vitamin A concentrations
      in healthy humans after carrot consumption.
AB  - Background: Asymmetric alpha-carotene, a provitamin A carotenoid, is cleaved to
      produce retinol (vitamin A) and alpha-retinol (with negligible vitamin A
      activity). The vitamin A activity of alpha-carotene-containing foods is likely
      overestimated because traditional analytic methods do not separate alpha-retinol
      derivatives from active retinol.Objective: This study aimed to accurately
      characterize intestinal alpha-carotene cleavage and its relative contribution to
      postprandial vitamin A in humans after consumption of raw carrots.Design: Healthy
      adults (n = 12) consumed a meal containing 300 g raw carrot (providing 27.3 mg
      beta-carotene and 18.7 mg alpha-carotene). Triglyceride-rich lipoprotein
      fractions of plasma were isolated and extracted, and alpha-retinyl palmitate
      (alphaRP) and retinyl palmitate were measured over 12 h postprandially via high
      performance liquid chromatography-tandem mass spectrometry. The complete profile
      of all alpha-retinyl esters and retinyl esters was measured at 6 h, and total
      absorption of alpha- and beta-carotene was calculated.Results: alphaRP was
      identified and quantified in every subject. No difference in preference for
      absorption of beta- over alpha-carotene was observed (adjusting for dose, 28%
      higher, P = 0.103). After absorption, beta-carotene trended toward preferential
      cleavage compared with alpha-carotene (22% higher, P = 0.084). A large range of
      provitamin A carotenoid conversion efficiencies was observed, with alpha-carotene
      contributing 12-35% of newly converted vitamin A (predicted contribution =
      25.5%). In all subjects, a majority of alpha-retinol was esterified to palmitic
      acid (as compared with other fatty acids).Conclusions: alpha-Retinol is
      esterified in the enterocyte and transported in the blood analogous to retinol.
      The percentage of absorption of alpha-carotene from raw carrots was not
      significantly different from beta-carotene when adjusting for dose, although a
      trend toward higher cleavage of beta-carotene was observed. The results
      demonstrate large interindividual variability in alpha-carotene conversion. The
      contribution of newly absorbed alpha-carotene to postprandial vitamin A should
      not be estimated but should be measured directly to accurately assess the vitamin
      A capacity of alpha-carotene-containing foods. This trial was registered at
      clinicaltrials.gov as NCT01432210.

PMID- 28515068
TI  - Low-fat dietary pattern and cardiovascular disease: results from the Women's
      Health Initiative randomized controlled trial.
AB  - Background: The influence of a low-fat dietary pattern on the cardiovascular
      health of postmenopausal women continues to be of public health
      interest.Objective: This report evaluates low-fat dietary pattern influences on
      cardiovascular disease (CVD) incidence and mortality during the intervention and
      postintervention phases of the Women's Health Initiative Dietary Modification
      Trial.Design: Participants comprised 48,835 postmenopausal women aged 50-79 y;
      40% were randomly assigned to a low-fat dietary pattern intervention (target of
      20% of energy from fat), and 60% were randomly assigned to a usual diet
      comparison group. The 8.3-y intervention period ended in March 2005, after which
      >80% of surviving participants consented to additional active follow-up through
      September 2010; all participants were followed for mortality through 2013. Breast
      and colorectal cancer were the primary trial outcomes, and coronary heart disease
      (CHD) and overall CVD were additional designated outcomes.Results: Incidence
      rates for CHD and total CVD did not differ between the intervention and
      comparison groups in either the intervention or postintervention period. However,
      CHD HRs comparing these groups varied strongly with baseline CVD and hypertension
      status. Participants without prior CVD had an intervention period CHD HR of 0.70
      (95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or
      hypertensive, respectively (P-interaction = 0.003). The CHD benefit among healthy
      normotensive women was partially offset by an increase in ischemic stroke risk.
      Corresponding HRs in the postintervention period were close to null. Participants
      with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61
      (95% CI: 1.02, 2.55) in the intervention and postintervention periods,
      respectively. However, various lines of evidence suggest that results in women
      with CVD or hypertension at baseline are confounded by postrandomization use of
      cholesterol-lowering medications.Conclusions: CVD risk in postmenopausal women
      appears to be sensitive to a change to a low-fat dietary pattern and, among
      healthy women, includes both CHD benefit and stroke risk. This trial was
      registered at clinicaltrials.gov as NCT00000611.

PMID- 28515069
TI  - Mendelian randomization shows sex-specific associations between long-chain PUFA
      related genotypes and cognitive performance in Danish schoolchildren.
AB  - Background: Dietary and endogenously formed long-chain polyunsaturated fatty
      acids (LCPUFAs) are hypothesized to improve cognitive development, but results
      are inconclusive, with suggestions of sex specificity. One study suggested that
      single-nucleotide polymorphisms (SNPs) rs1535 and rs174448 in the fatty acid
      desaturase (FADS) gene cluster have opposite effects on erythrocyte LCPUFAs at 9
      mo.Objective: To explore whether SNPs in FADS and elongase (ELOVL) genes were
      associated with school performance in a sex-specific manner, we performed a
      Mendelian randomization study using data from the Optimal well-being, development
      and health for Danish children through a healthy New Nordic Diet (OPUS) School
      Meal Study with 765 Danish schoolchildren 8-11 y old.Design: Associations between
      selected FADS1/2 SNPs (rs1535, rs174448, and rs174468) and ELOVL5 rs2397142,
      whole-blood fatty acid composition, and performance in the d2 Test of Attention
      and a reading test were analyzed in multiple regression models including all
      SNPs, SNP-sex interactions, and covariates related to testing
      conditions.Results:FADS, rs1535 minor allele carriage associated with lower whole
      blood arachidonic acid (P <= 0.002), and minor alleles of rs174448 tended to
      associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex
      interactions in 50% of the SNP performance sets. Sex-dependent associations were
      observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P < 0.03)
      and for the associations between reading scores and rs174448 and rs2397142 (P <
      0.01). All of the sex-specific analyses showed associations in opposite
      directions in girls and boys. The minor allele carriage of rs174448 was
      associated with lower d2 Test of Attention performance (P < 0.02) and reading
      scores (P < 0.001) in boys but with better reading scores in girls (P <= 0.002).
      The associations were consistently the opposite for rs1535 minor allele carriage
      (P < 0.05). Associations with rs2397142 also appeared to be opposite of those of
      rs174448, but only for reading and not significant after adjustment for parental
      educational level and whole-blood DHA.Conclusions: This study showed associations
      between rs1535 minor allele homozygosity and rs174448 major allele carriage and
      improved performance in 8- to 11-y-old boys but not in girls, thereby
      counteracting existing sex differences. This may be a consequence of increased
      endogenous DHA synthesis in infancy but not at school-age. This trial was
      registered at clinicaltrials.gov as NCT01457794.

PMID- 28515070
TI  - Even mealtime distribution of protein intake is associated with greater muscle
      strength, but not with 3-y physical function decline, in free-living older
      adults: the Quebec longitudinal study on Nutrition as a Determinant of Successful
      Aging (NuAge study).
AB  - Background: Functional status declines with aging, thus impeding autonomy.
      Recently, a more even mealtime distribution of dietary protein was positively
      associated with muscle mass, but the relation of this distribution to physical
      performance remains unknown.Objective: We examined the relation between mealtime
      protein-intake distribution and physical performance and its 3-y decline in
      community-dwelling older adults.Design: Three-year follow-up data from 827 men
      and 914 women (67-84 y) in the longitudinal study on nutrition and aging [Quebec
      longitudinal study on Nutrition as a Determinant of Successful Aging (NuAge
      study); Quebec, Canada] were analyzed. Physical performance, which was measured
      yearly, was grouped into the following 2 functional composite scores: muscle
      strength (handgrip, arm, and leg) and mobility (timed-up-and-go, chair stand, and
      walking speed). Dietary data were collected in 2 sets of three 24-h food recalls
      at baseline and year 2. The individual mealtime protein distribution was
      calculated as the CV (i.e., SD divided by the mean) of grams of protein per meal.
      A mixed model analysis was used to examine trajectories of muscle strength and
      mobility across time by sex as conditioned by the protein distribution and
      adjusted for potential covariates.Results: Physical performance deteriorated over
      3 y with muscle strength declining more than the mobility score in men (-1.51 +/-
      1.68 compared with -0.66 +/- 2.81) and women (-1.35 +/- 1.77 compared with -0.78
      +/- 2.63) (means +/- SD, P < 0.001). More-evenly distributed protein intake,
      independent of the total quantity, was associated with a higher muscle-strength
      score in both sexes throughout follow-up. It was also associated with a greater
      mobility score, but only in men and only before adjustment for covariates.
      Strength and mobility rates of decline were not affected by protein-intake
      distribution in either sex.Conclusions: In addition to the previously observed
      association with lean mass, an even distribution of daily protein intake across
      meals is independently associated with greater muscle strength, but not with the
      mobility score, in older adults. A longer-term investigation of the role of
      protein intake and its distribution on physical performance is warranted, as are
      intervention studies, to support future recommendations.

PMID- 28515071
TI  - Challenges in defining the role of dietary protein in bone health.

PMID- 28515073
TI  - Monsters and angels.

PMID- 28515074
TI  - Immune checkpoints on innate lymphoid cells.
AB  - In this issue of JEM, Taylor et al. (https://doi.org/10.1084/jem.20161653)
      describe PD-1 as a critical negative regulator of group 2 innate lymphoid cells
      (ILC-2s). PD-1 intrinsically controls proliferation and cytokine production of
      both mouse and human ILC-2s. PD-1 signaling inhibits STAT5 phosphorylation and
      the removal of this brake by knocking down PD-1 expression or by using anti-PD-1
      blocking antibodies, translated in vivo into better clearance of helminth worm
      infection in mice.

PMID- 28515076
TI  - Vertically transmitted symbionts as mechanisms of transgenerational effects.
AB  - PREMISE OF THE STUDY: A transgenerational effect occurs when a biotic or abiotic
      environmental factor acts on a parental individual and thereby affects the
      phenotype of progeny. Due to the importance of transgenerational effects for
      understanding plant ecology and evolution, their underlying mechanisms are of
      general interest. Here, we introduce the concept that inherited symbiotic
      microorganisms could act as mechanisms of transgenerational effects in plants.
      METHODS: We define the criteria required to demonstrate that transgenerational
      effects are microbially mediated and review evidence from the well-studied,
      vertically transmitted plant-fungal symbiosis (grass-Epichloe spp.) in support of
      such effects. We also propose a basic experimental design to test for the
      presence of adaptive transgenerational effects mediated by plant symbionts. KEY
      RESULTS: An increasingly large body of literature shows that vertically
      transmitted microorganisms are common in plants, with potential to affect the
      phenotypes and fitness of progeny. Transgenerational effects could occur via
      parental modification of symbiont presence/absence, symbiont load, symbiont
      products, symbiont genotype or species composition, or symbiont priming. Several
      of these mechanisms appear likely in the grass-Epichloe endophytic symbiosis, as
      there is variation in the proportion of the progeny that carries the fungus, as
      well as variation in concentrations of mycelia and secondary compounds (alkaloids
      and osmolytes) in the seed. CONCLUSIONS: Symbiont-mediated transgenerational
      effects could be common in plants and could play large roles in plant adaptation
      to changing environments, but definitive tests are needed. We hope our
      contribution will spark new lines of research on the transgenerational effects of
      vertically transmitted symbionts in plants.

PMID- 28515075
TI  - pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial
      brain invasion.
AB  - Streptococcus pneumoniae is the main cause of bacterial meningitis, a life
      threating disease with a high case fatality rate despite treatment with
      antibiotics. Pneumococci cause meningitis by invading the blood and penetrating
      the blood-brain barrier (BBB). Using stimulated emission depletion (STED) super
      resolution microscopy of brain biopsies from patients who died of pneumococcal
      meningitis, we observe that pneumococci colocalize with the two BBB endothelial
      receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell
      adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal
      pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC
      binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis
      model and mutant mice, as well as antibodies against the two receptors, we
      prevent pneumococcal entry into the brain and meningitis development. By adding
      antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the
      bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM
      1 has the potential to prevent pneumococcal meningitis.

PMID- 28515072
TI  - omega-3 and omega-6 long-chain PUFAs and their enzymatic metabolites in
      neovascular eye diseases.
AB  - Neovascular eye diseases, including retinopathy of prematurity, diabetic
      retinopathy, and age-related macular degeneration, threaten the visual health of
      children and adults. Current treatment options, including anti-vascular
      endothelial growth factor therapy and laser retinal photocoagulation, have
      limitations and are associated with adverse effects; therefore, the
      identification of additional therapies is highly desirable. Both clinical and
      experimental studies show that dietary omega-3 (n-3) long-chain polyunsaturated
      fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis. The omega-3 LC
      PUFA metabolites from 2 groups of enzymes, cyclooxygenases and lipoxygenases,
      inhibit [and the omega-6 (n-6) LC-PUFA metabolites promote] inflammation and
      angiogenesis. However, both of the omega-3 and the omega-6 lipid products of
      cytochrome P450 oxidase 2C promote neovascularization in both the retina and
      choroid, which suggests that inhibition of this pathway might be beneficial. This
      review summarizes our current understanding of the roles of omega-3 and omega-6
      LC-PUFAs and their enzymatic metabolites in neovascular eye diseases.

PMID- 28515077
TI  - Toward principles of historical ecology.

PMID- 28515078
TI  - Shifting Quaternary migration patterns in the Bahamian archipelago: Evidence from
      the Zamia pumila complex at the northern limits of the Caribbean island
      biodiversity hotspot.
AB  - PREMISE OF THE STUDY: The Bahamas archipelago is formed by young, tectonically
      stable carbonate banks that harbor direct geological evidence of global ice
      volume changes. We sought to detect signatures of major changes on gene flow
      patterns and reconstruct the phylogeographic history of the monophyletic Zamia
      pumila complex across the Bahamas. METHODS: Nuclear molecular markers with both
      high and low mutation rates were used to capture two different time scale
      signatures and test several gene flow and demographic hypotheses. KEY RESULTS:
      Single-copy nuclear genes unveiled apparent ancestral admixture on Andros,
      suggesting a significant role of this island as main hub of diversity of the
      archipelago. We detected demographic and spatial expansion of the Zamia pumila
      complex on both paleo-provinces around the Piacenzian (Pliocene)/Gelasian
      (Pleistocene). Populations evidenced signatures of different migration models
      that have occurred at two different times. Populations on Long Island (Z.
      lucayana) may either represent a secondary colonization of the Bahamas by Zamia
      or a rapid and early-divergence event of at least one population on the Bahamas.
      CONCLUSIONS: Despite changes in migration patterns with global climate, expected
      heterozygosity with both marker systems remains within the range reported for
      cycads, but with significant levels of increased inbreeding detected by the
      microsatellites. This finding is likely associated with reduced gene flow between
      and within paleo-provinces, accompanied by genetic drift, as rising seas enforced
      isolation. Our study highlights the importance of the maintenance of the
      predominant direction of genetic exchange and the role of overseas dispersion
      among the islands during climate oscillations.

PMID- 28515079
TI  - Impact of acetaminophen consumption and resistance exercise on extracellular
      matrix gene expression in human skeletal muscle.
AB  - Acetaminophen (APAP) given during chronic exercise reduces skeletal muscle
      collagen and cross-linking in rats. We propose that the effect of APAP on muscle
      extracellular matrix (ECM) may, in part, be mediated by dysregulation of the
      balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs
      (TIMPs). The purpose of this study was to evaluate the impact of APAP consumption
      during acute resistance exercise (RE) on several regulators of the ECM in human
      skeletal muscle. In a double-blinded, placebo-controlled, randomized crossover
      design, recreationally active men (n = 8, 25 +/- 2 yr) performed two trials of
      knee extension. Placebo (PLA) or APAP (1,000 mg/6 h) was given for 24 h before
      and immediately following RE. Vastus lateralis biopsies were taken at baseline
      and 1 and 3 h post-RE. Quantitative RT-PCR was used to determine differences in
      mRNA expression. MMP-2, type I collagen, and type III collagen mRNA expression
      was not altered by exercise or APAP (P > 0.05). When compared with PLA, TIMP-1
      expression was lower at 1 h post-RE during APAP conditions but greater than PLA
      at 3 h post-RE (P < 0.05). MMP-9 expression and protein levels were elevated at 3
      h post-RE independent of treatment (P < 0.05). Lysyl oxidase expression was
      greater at 3 h post-RE during APAP consumption (P < 0.05) compared with PLA. MMP
      2 and TIMP-1 protein was not altered by RE or APAP (P > 0.05). Phosphorylation of
      ERK1/2 and p38-MAPK increased (P < 0.05) with RE but was not influenced by APAP.
      Our findings do not support our hypothesis and suggest that short-term APAP
      consumption before RE has a small impact on the measured ECM molecules in human
      skeletal muscle following acute RE.

PMID- 28515080
TI  - Effect of resistance exercise under conditions of reduced blood insulin on
      AMPKalpha Ser485/491 inhibitory phosphorylation and AMPK pathway activation.
AB  - Insulin stimulates skeletal muscle glucose uptake via activation of the protein
      kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP
      activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the
      AMPK alpha-subunit. Thus lower blood insulin concentrations may induce AMPK
      signal activation. Acute exercise is one method to stimulate AMPK activation;
      however, no study has examined the relationship between blood insulin levels and
      acute resistance exercise-induced AMPK pathway activation. Based on previous
      findings, we hypothesized that the acute resistance exercise-induced AMPK pathway
      activation would be augmented by disruptions in insulin secretion through a
      decrease in AMPKalpha Ser485/491 inhibitory phosphorylation. To test the
      hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin
      streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting beta-cells. Three
      days postinjection, the right gastrocnemius muscle from STZ and control rats was
      subjected to resistance exercise by percutaneous electrical stimulation. Animals
      were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream
      pathways in the muscle tissue was analyzed by Western blotting and real-time PCR.
      Notably, STZ rats showed a significant decrease in basal Akt and AMPKalpha
      Ser485/491 phosphorylation, but substantial exercise-induced increases in both
      AMPKalpha Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were
      observed. Although no significant impact on resistance exercise-induced Akt
      pathway activation or glucose uptake was found, resistance exercise-induced
      peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 alpha (PGC
      1alpha) gene expression was augmented by STZ treatment. Collectively, these data
      suggest that circulating insulin levels may regulate acute resistance exercise
      induced AMPK pathway activation and AMPK-dependent gene expression relating to
      basal AMPKalpha Ser485/491 phosphorylation.

PMID- 28515082
TI  - Parkin-independent mitophagy-FKBP8 takes the stage.
AB  - Although the Parkin/PINK1 pathway has received considerable attention in recent
      years as a key regulator of mitophagy in mammals, it is important to recognize
      that multiple mitophagy receptors like BNIP3, NIX, and FUNDC1 exist that can
      promote the selective clearance of mitochondria in the absence of Parkin. In this
      issue, Bhujabal et al expand the repertoire of Parkin-independent mitophagy
      receptors to include the anti-apoptotic protein, FKBP8. The authors demonstrate
      that FKBP8 interacts preferentially with LC3A via its LIR motif to destroy
      damaged mitochondria. During the process, FKBP8 escapes from the destruction
      presumably to prevent apoptosis during mitophagy [1].

PMID- 28515081
TI  - Flexible ammonia handling strategies using both cutaneous and branchial epithelia
      in the highly ammonia-tolerant Pacific hagfish.
AB  - Hagfish consume carrion, potentially exposing them to hypoxia, hypercapnia, and
      high environmental ammonia (HEA). We investigated branchial and cutaneous ammonia
      handling strategies by which Pacific hagfish (Eptatretus stoutii) tolerate and
      recover from high ammonia loading. Hagfish were exposed to HEA (20 mmol/l) for 48
      h to elevate plasma total ammonia (TAmm) levels before placement into divided
      chambers for a 4-h recovery period in ammonia-free seawater where ammonia
      excretion (JAmm) was measured independently in the anterior and posterior
      compartments. Localized HEA exposures were also conducted by subjecting hagfish
      to HEA in either the anterior or posterior compartments. During recovery, HEA
      exposed animals increased JAmm in both compartments, with the posterior
      compartment comprising ~20% of the total JAmm compared with ~11% in non-HEA
      exposed fish. Plasma TAmm increased substantially when whole hagfish and the
      posterior regions were exposed to HEA. Alternatively, plasma TAmm did not elevate
      after anterior localized HEA exposure. JAmm was concentration dependent (0.05-5
      mmol/l) across excised skin patches at up to eightfold greater rates than in skin
      sections that were excised from HEA-exposed hagfish. Skin excised from more
      posterior regions displayed greater JAmm than those from more anterior regions.
      Immunohistochemistry with hagfish-specific anti-rhesus glycoprotein type c (alpha
      hRhcg; ammonia transporter) antibody was characterized by staining on the basal
      aspect of hagfish epidermis while Western blotting demonstrated greater
      expression of Rhcg in more posterior skin sections. We conclude that cutaneous
      Rhcg proteins are involved in cutaneous ammonia excretion by Pacific hagfish and
      that this mechanism could be particularly important during feeding.

PMID- 28515083
TI  - Self-healing capacity of deep-sea ecosystems affected by petroleum hydrocarbons:
      Understanding microbial oil degradation at hydrocarbon seeps is key to
      sustainable bioremediation protocols.

PMID- 28515084
TI  - Novel diagnostic technologies for clinical and frontline use: Advanced
      diagnostics based on molecular markers and analysis technologies has been
      improving diagnosis across a wide range of diseases.

PMID- 28515086
TI  - Multi-omics and Alzheimer's disease: a slower but surer path to an efficacious
      therapy?

PMID- 28515085
TI  - Regulation of ATP production: dependence on calcium concentration and respiratory
      state.
AB  - Nanomolar free calcium enhances oxidative phosphorylation. However, the effects
      over a broad concentration range, at different respiratory states, or on specific
      energy substrates are less clear. We examined the action of varying [Ca2+] over
      respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration,
      potential, ATP production, and H2O2 production using ADP recycling to clamp
      external [ADP]. Calcium at 450 nM enhanced respiration in mitochondria energized
      by the complex I substrates, glutamate/malate (but not succinate), at [ADP] of 4
      256 uM, but more substantially at intermediate respiratory states and not at all
      at state 4. Using varied [Ca2+], we found that the stimulatory effects on
      respiration and ATP production were most prominent at nanomolar concentrations,
      but inhibitory at 10 uM or higher. ATP production decreased more than respiration
      at 10 uM calcium. However, potential continued to increase up to 10 uM;
      suggesting a calcium-induced inability to utilize potential for phosphorylation
      independent of opening of the mitochondrial permeability transition pore (MTP).
      This effect of 10 uM calcium was confirmed by direct determination of ATP
      production over a range of potential created by differing substrate
      concentrations. Consistent with past reports, nanomolar [Ca2+] had a stimulatory
      effect on utilization of potential for phosphorylation. Increasing [Ca2+] was
      positively and continuously associated with H2O2 production. In summary, the
      stimulatory effect of calcium on mitochondrial function is substrate dependent
      and most prominent over intermediate respiratory states. Calcium stimulates or
      inhibits utilization of potential for phosphorylation dependent on concentration
      with inhibition at higher concentration independent of MTP opening.

PMID- 28515087
TI  - FXYD5 (dysadherin) may mediate metastatic progression through regulation of the
      beta-Na+-K+-ATPase subunit in the 4T1 mouse breast cancer model.
AB  - FXYD5 is a Na+-K+-ATPase regulator, expressed in a variety of normal epithelia.
      In parallel, it has been found to be associated with several types of cancer and
      effect lethal outcome by promoting metastasis. However, the molecular mechanism
      underlying FXYD5 mediated invasion has not yet been identified. In this study,
      using in vivo 4T1 murine breast cancer model, we found that FXYD5-specific shRNA
      significantly inhibited lung cancer metastasis, without having a substantial
      effect on primary tumor growth. Our study reveals that FXYD5 participates in
      multiple stages of metastatic development and exhibits more than one mode of E
      cadherin regulation. We provide the first evidence that FXYD5-related
      morphological changes are mediated through its interaction with Na+-K+-ATPase.
      Experiments in cultured 4T1 cells have indicated that FXYD5 expression may
      downregulate the beta1 isoform of the pump. This behavior could have implications
      on both transcellular interactions and intracellular events. Further studies
      suggest that differential localization of the adaptor protein Annexin A2 in FXYD5
      expressing cells may correlate with matrix metalloproteinase 9 secretion and
      adhesion changes in 4T1 wild-type cells.

PMID- 28515088
TI  - Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in
      renal proximal tubule cells from rat models of hypertension: aged F344 rats and
      spontaneously hypertensive rats.
AB  - Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation
      and endocytosis of the NKA alpha1. Dopamine-mediated regulation of NKA is
      impaired in aging and some forms of hypertension. Using opossum (OK) proximal
      tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory
      factor-1 (NHERF-1) associates with NKA alpha1 and dopamine-1 receptor (D1R). This
      association is required for the dopamine-mediated regulation of NKA. In OK cells,
      dopamine decreases NHERF-1 association with NKA alpha1 but increases its
      association with D1R. However, it is not known whether NHERF-1 plays a role in
      dopamine-mediated NKA regulation in animal models of hypertension. We
      hypothesized that defective dopamine-mediated regulation of NKA results from the
      decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of
      hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test
      this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and
      their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls,
      normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both
      hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated
      phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced.
      Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine
      mediated inhibition of NKA. These results suggest that decreased renal NHERF-1
      expression contributes to the impaired dopamine-mediated inhibition of NKA in
      PTCs from animal models of hypertension.

PMID- 28515090
TI  - NF-kappaB p50 (nfkb1) contributes to pathogenesis in the EMU-TCL1 mouse model of
      chronic lymphocytic leukemia.

PMID- 28515089
TI  - The NH2 terminus regulates voltage-dependent gating of CALHM ion channels.
AB  - Calcium homeostasis modulator protein-1 (CALHM1) and its Caenorhabditis elegans
      (ce) homolog, CLHM-1, belong to a new family of physiologically important ion
      channels that are regulated by voltage and extracellular Ca2+ (Ca2+o) but lack a
      canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent
      gating mechanisms for CALHM channels are unknown. Here, we performed voltage
      clamp experiments on ceCLHM-1 chimeric, deletion, insertion, and point mutants to
      assess the role of the NH2 terminus (NT) in CALHM channel gating. Analyses of
      chimeric channels in which the ceCLHM-1 and human (h)CALHM1 NH2 termini were
      interchanged showed that the hCALHM1 NT destabilized channel-closed states,
      whereas the ceCLHM-1 NT had a stabilizing effect. In the absence of Ca2+o,
      deletion of up to eight amino acids from the ceCLHM-1 NT caused a hyperpolarizing
      shift in the conductance-voltage relationship with little effect on voltage
      dependent slope. However, deletion of nine or more amino acids decreased voltage
      dependence and induced a residual conductance at hyperpolarized voltages.
      Insertion of amino acids into the NH2-terminal helix also decreased voltage
      dependence but did not prevent channel closure. Mutation of ceCLHM-1 valine 9 and
      glutamine 13 altered half-maximal activation and voltage dependence,
      respectively, in 0 Ca2+ In 2 mM Ca2+o, ceCLHM-1 NH2-terminal deletion and point
      mutant channels closed completely at hyperpolarized voltages with apparent
      affinity for Ca2+o indistinguishable from wild-type ceCLHM-1, although the ceCLHM
      1 valine 9 mutant exhibited an altered conductance-voltage relationship and
      kinetics. We conclude that the NT plays critical roles modulating voltage
      dependence and stabilizing the closed states of CALHM channels.

PMID- 28515092
TI  - Human CD62Ldim neutrophils identified as a separate subset by proteome profiling
      and in vivo pulse-chase labeling.
AB  - During acute inflammation, 3 neutrophil subsets are found in the blood:
      neutrophils with a conventional segmented nucleus, neutrophils with a banded
      nucleus, and T-cell-suppressing CD62Ldim neutrophils with a high number of
      nuclear lobes. In this study, we compared the in vivo kinetics and proteomes of
      banded, mature, and hypersegmented neutrophils to determine whether these cell
      types represent truly different neutrophil subsets or reflect changes induced by
      lipopolysaccharide (LPS) activation. Using in vivo pulse-chase labeling of
      neutrophil DNA with 6,6-2H2-glucose, we found that 2H-labeled banded neutrophils
      appeared much earlier in blood than labeled CD62Ldim and segmented neutrophils,
      which shared similar label kinetics. Comparison of the proteomes by cluster
      analysis revealed that CD62Ldim neutrophils were clearly separate from
      conventional segmented neutrophils despite having similar kinetics in peripheral
      blood. Interestingly, the conventional segmented cells were more related at a
      proteome level to banded cells despite a 2-day difference in maturation time. The
      differences between CD62Ldim and mature neutrophils are unlikely to have been a
      direct result of LPS-induced activation, because of the extremely low
      transcriptional capacity of CD62Ldim neutrophils and the fact that neutrophils do
      not directly respond to the low dose of LPS used in the study (2 ng/kg body
      weight). Therefore, we propose CD62Ldim neutrophils are a truly separate
      neutrophil subset that is recruited to the bloodstream in response to acute
      inflammation. This trial was registered at www.clinicaltrials.gov as
      #NCT01766414.

PMID- 28515091
TI  - Angiotensin-converting enzyme enhances the oxidative response and bactericidal
      activity of neutrophils.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are widely used to reduce blood
      pressure. Here, we examined if an ACE is important for the antibacterial
      effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE
      inhibitor were more susceptible to bacterial infection by methicillin-resistant
      Staphylococcus aureus (MRSA). In contrast, mice overexpressing ACE in neutrophils
      (NeuACE mice) have increased resistance to MRSA and better in vitro killing of
      MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae ACE overexpression
      increased neutrophil production of reactive oxygen species (ROS) following MRSA
      challenge, an effect independent of the angiotensin II AT1 receptor.
      Specifically, as compared with wild-type (WT) mice, there was a marked increase
      of superoxide generation (>twofold, P < .0005) in NeuACE neutrophils following
      infection, whereas ACE knockout neutrophils decreased superoxide production.
      Analysis of membrane p47-phox and p67-phox indicates that ACE increases reduced
      NAD phosphate oxidase activity but does not increase expression of these
      subunits. Increased ROS generation mediates the enhanced bacterial resistance of
      NeuACE mice because the enhanced resistance is lost with DPI (an inhibitor of ROS
      production by flavoenzymes) inhibition. NeuACE granulocytes also have increased
      neutrophil extracellular trap formation and interleukin-1beta release in response
      to MRSA. In a mouse model of chemotherapy-induced neutrophil depletion,
      transfusion of ACE-overexpressing neutrophils was superior to WT neutrophils in
      treating MRSA infection. These data indicate a previously unknown function of ACE
      in neutrophil antibacterial defenses and suggest caution in the treatment of
      certain individuals with ACE inhibitors. ACE overexpression in neutrophils may be
      useful in boosting the immune response to antibiotic-resistant bacterial
      infection.

PMID- 28515093
TI  - Circulating soluble P-selectin must dimerize to promote inflammation and
      coagulation in mice.
AB  - Leukocyte adhesion to P-selectin on activated platelets and endothelial cells
      induces shedding of the P-selectin ectodomain into the circulation. Plasma
      soluble P-selectin (sP-selectin) is elevated threefold to fourfold in patients
      with cardiovascular disease. Circulating sP-selectin is thought to trigger
      signaling in leukocytes that directly contributes to inflammation and thrombosis.
      However, sP-selectin likely circulates as a monomer, and in vitro studies suggest
      that sP-selectin must dimerize to induce signaling in leukocytes. To address this
      discrepancy, we expressed the entire ectodomain of mouse P-selectin as a monomer
      (sP-selectin) or as a disulfide-linked dimer fused to the Fc portion of mouse
      immunoglobulin G (sP-selectin-Fc). Dimeric sP-selectin-Fc, but not monomeric sP
      selectin, triggered integrin-dependent adhesion of mouse leukocytes in vitro.
      Antibody-induced oligomerization of sP-selectin or sP-selectin-Fc was required to
      trigger formation of neutrophil extracellular traps. Injecting sP-selectin-Fc,
      but not sP-selectin, into mice augmented integrin-dependent adhesion of
      neutrophils in venules, generated tissue factor-bearing microparticles, shortened
      plasma-clotting times, and increased thrombus frequency in the inferior vena
      cava. Furthermore, transgenic mice that overexpressed monomeric sP-selectin did
      not exhibit increased inflammation or thrombosis. We conclude that elevated
      plasma sP-selectin is a consequence rather than a cause of cardiovascular
      disease.

PMID- 28515096
TI  - Leveraging Human Genetics to Understand the Relation of LDL Cholesterol with Type
      2 Diabetes.

PMID- 28515095
TI  - Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma.
AB  - Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes:
      acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a
      novel prognostic index (PI) for chronic and smoldering ATL. We conducted a
      nationwide retrospective survey on ATL patients, and 248 fully eligible
      individuals were used in this analysis. In the univariate analysis, sex,
      performance status, log10 (soluble interleukin-2 receptor [sIL-2R]), neutrophils
      count, and lymphadenopathy showed values of P < .05 in training samples. A
      multivariate analysis was performed on these factors, and only log10 (sIL-2R) was
      identified as an independent prognostic factor in training samples. Using a
      regression coefficient of this variable, a prognostic model was formulated to
      identify different levels of risk: indolent ATL-PI (iATL-PI) = 1.51 * log10 (sIL
      2R [U/mL]). The values calculated by iATL-PI were divided into 3 groups using a
      quartile point. In the validation sample, median survival times (MSTs) were 1.6
      years, 5.5 years, and not reached for patients in the high-, intermediate-, and
      low-risk groups, respectively (P < .0001). To make the scoring system clinically
      practicable, we simplified iATL-PI according to trichotomizing sIL-2R at 1000 and
      6000 U/mL, using a quartile point. Patients with more than 6000 U/mL sIL-2R were
      categorized into the high-risk group, less than and equal to 1000 U/mL into the
      low-risk group, and the others into the intermediate-risk group, and MSTs were
      1.6 years, not reached, and 5.5 years, respectively (P < .0001). iATL-PI has
      potential as a novel tool for a risk-adapted therapeutic approach.

PMID- 28515097
TI  - The Phoenix Rises: The Rebirth of Cancer Immunotherapy.

PMID- 28515094
TI  - Inhibiting the osteocyte-specific protein sclerostin increases bone mass and
      fracture resistance in multiple myeloma.
AB  - Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton
      causing profound bone destruction and fractures. The bone disease is mediated by
      increased osteoclastic bone resorption and suppressed bone formation.
      Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss
      but fail to influence bone formation and do not replace lost bone, so patients
      continue to fracture. Stimulating bone formation to increase bone mass and
      fracture resistance is a priority; however, targeting tumor-derived modulators of
      bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt
      antagonist that inhibits bone formation. We hypothesized that inhibiting
      sclerostin would prevent development of bone disease and increase resistance to
      fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and
      myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells
      from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1
      eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was
      associated with a decrease in fracture resistance in the vertebrae. Treatment
      with anti-sclerostin antibody increased osteoblast numbers and bone formation
      rate but did not inhibit bone resorption or reduce tumor burden. Treatment with
      anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic
      bone lesions, and increased fracture resistance. Treatment with anti-sclerostin
      antibody and zoledronic acid combined increased bone mass and fracture resistance
      when compared with treatment with zoledronic acid alone. This study defines a
      therapeutic strategy superior to the current standard of care that will reduce
      fractures for patients with MM.

PMID- 28515098
TI  - Collagen Turnover Markers in Relation to Future Cardiovascular and
      Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Sustained remodeling of extracellular matrix can compromise organs
      and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen
      type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and
      degradation. We studied their predictive value for future death and disease.
      METHODS: A total of 3068 men and women in the Multi-Ethnic Study of
      Atherosclerosis who were free of cardiovascular disease (CVD) and in generally
      good health had a baseline blood sample taken for ICTP and PIIINP. Median follow
      up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were
      adjudicated, death (n = 571) was by death certificate, and chronic inflammatory
      related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n =
      327) were classified using International Classification of Diseases codes. We
      used Poisson regression to study baseline ICTP and PIIINP relative to these
      outcomes. RESULTS: Mean (SD) PIIINP was 5.47 (1.95) MUg/L and ICTP was 3.37
      (1.70) MUg/L. PIIINP and ICTP were highly correlated with each other and with
      estimated glomerular filtration rate (eGFR). Adjustment for age and eGFR
      attenuated relative risks, remaining 20%-30% per SD of both PIIINP and ICTP in
      prediction for total death and ChrIRD, and of PIIINP for cancer, with little
      additional attenuation by adjusting for risk factors and inflammatory biomarkers.
      CVD outcome was generally unrelated to PIIINP but became marginally inversely
      related to ICTP in the most adjusted model. CONCLUSIONS: The collagen biomarkers
      PIIINP and ICTP, in part through pathophysiologically parallel associations with
      renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted
      future cancer. These collagen markers may help differentiate healthy from
      unhealthy aging.

PMID- 28515101
TI  - Laboratory Formulary: A Model for High-Value Evidence-Based Medicine.

PMID- 28515099
TI  - Temporal Biomarker Profiling Reveals Longitudinal Changes in Risk of Death or
      Myocardial Infarction in Non-ST-Segment Elevation Acute Coronary Syndrome.
AB  - BACKGROUND: There are conflicting data on whether changes in N-terminal pro-B
      type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs
      CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are
      associated with a change in prognosis. METHODS: We measured NT-proBNP and hs-CRP
      at 3 time points in 1665 patients with non-ST-segment elevation acute coronary
      syndrome (NSTEACS). Cox proportional hazards was applied to the delta between
      temporal measurements to determine the continuous association with cardiovascular
      events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40%
      increase as the basic unit of temporal change. RESULTS: Median NT-proBNP was
      370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0
      (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and
      1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas
      between baseline and 6 months were the most prognostically informative. Every
      +40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14%
      greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI,
      1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95%
      CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months)
      was associated with a 9% greater risk of the composite end point (adjusted HR
      1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction
      (adjusted HR 1.10, 95%, CI 1.00-1.20). CONCLUSIONS: Temporal changes in NT-proBNP
      and hs-CRP are quantitatively associated with future cardiovascular events,
      supporting their role in dynamic risk stratification of NSTEACS. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT00699998.

PMID- 28515102
TI  - American Liver Guidelines and Cutoffs for "Normal" ALT: A Potential for
      Overdiagnosis.

PMID- 28515103
TI  - Serial Measurement of Biomarkers after Acute Coronary Syndrome: Which One to
      Choose?

PMID- 28515100
TI  - Detection of Chromosomal Translocation in Hematologic Malignancies by a Novel DNA
      Based Looped Ligation Assay (LOLA).
AB  - BACKGROUND: Disease-defining chromosomal translocations are seen in various
      neoplasms, especially in lymphomas and leukemias. Translocation detection at the
      DNA level is often complicated by chromosomal breakpoints that are distributed
      over very large regions. We have developed a ligation-based assay [the looped
      ligation assay (LOLA)] to detect translocations from diseases with multiple
      widely spaced breakpoint hot spots. METHODS: Oligonucleotide sets that probe
      breakpoints of IGH-BCL2 (immunoglobulin heavy-apoptosis regulator) in follicular
      lymphoma (FL), MYC-IGH (MYC proto-oncogene, bHLH transcription factor
      immunoglobulin heavy) in Burkitt lymphoma (BL) and BCR-ABL1 (RhoGEF and GTPase
      activating protein-ABL proto-oncogene 1, non-receptor tyrosine kinase) in chronic
      myelogenous leukemia (CML) were designed. DNA from cell lines with these
      translocations was mixed with oligonucleotides in a single-step ligation reaction
      followed by PCR amplification. Detection was by capillary electrophoresis. We
      also tested peripheral blood from 16 CML patients and frozen tissue from 17 FL
      cases, and the results were compared to reverse transcription (RT)-PCR (CML) or
      fluorescent in situ hybridization (FISH) and delta-PCR (FL). RESULTS: LOLA
      produced signals of the expected sizes for the cell lines. Normal control DNA
      yielded no signals. A dilution series yielded translocation-specific peaks at
      dilutions as low as 1%. Signal intensity was log linear to the DNA concentration
      (R2 = 0.94). Furthermore, we were able to detect a LOLA peak in DNA from 53.3% of
      FL patients and 87.5% of CML patients. The concordance between LOLA, FISH, and
      delta-PCR in FL was also excellent. CONCLUSIONS: Our results indicate that LOLA
      is a simple method that is useful for DNA-based detection of translocations in
      challenging situations, particularly where the breakpoints are not tightly
      clustered. The assay also has the added benefit of permitting rapid mapping of
      the breakpoints.

PMID- 28515104
TI  - Pseudohypocalcemia in Cancer Patients: A Recommendation for the Postanalytical
      Correction of Serum Calcium in Patients with Hypoalbuminemia.

PMID- 28515106
TI  - Direct Comparison of 2 Rule-Out Strategies for Acute Myocardial Infarction: 2-h
      Accelerated Diagnostic Protocol vs 2-h Algorithm.
AB  - BACKGROUND: We compared 2 high-sensitivity cardiac troponin (hs-cTn)-based 2-h
      strategies in patients presenting with suspected acute myocardial infarction
      (AMI) to the emergency department (ED): the 2-h accelerated diagnostic protocol
      (2h-ADP) combining hs-cTn, electrocardiogram, and a risk score, and the 2-h
      algorithm exclusively based on hs-cTn concentrations and their absolute changes.
      METHODS: Analyses were performed in 2 independent diagnostic cohorts [European
      Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) study,
      Australian-New Zealand 2-h Accelerated Diagnostic Protocol to Assess patients
      with chest Pain symptoms using contemporary Troponins as the only biomarker
      (ADAPT) study] employing hs-cTnT (Elecsys) and hs-cTnI (Architect). The final
      diagnosis was adjudicated by 2 independent cardiologists. RESULTS: AMI was the
      final diagnosis in 16.5% (95% CI, 14.6%-18.6%) of the 1372 patients in APACE, and
      12.6% (95% CI, 10.7%-14.7%) of 1153 patients in ADAPT. The negative predictive
      value (NPV) and sensitivity for AMI were very high and comparable with both
      strategies using either hs-cTnT or hs-cTnI in both cohorts (all statistical
      comparisons nonsignificant). The percentage of patients triaged toward rule-out
      was significantly lower with the 2h-ADP (36%-43%) vs the 2-h algorithm (55%-68%)
      with both assays and in both cohorts (P < 0.001). The sensitivity of the 2h-ADP
      was higher for 30-day major adverse cardiovascular events. CONCLUSIONS: Both
      algorithms provided very high and comparable safety as quantified by the NPV and
      sensitivity for AMI and major adverse cardiac events (MACE) at 30 days in
      patients triaged toward rule-out, although sensitivity for MACE at 30 days was
      lower with both algorithms in cohort 2. Although the 2-h algorithm was more
      efficacious, not all patients ruled out for AMI by this algorithm were
      appropriate candidates for early discharge. The 2h-ADP seems superior in the
      selection of patients for early discharge from the ED. CLINICAL TRIAL
      REGISTRATION: APACE: http://clinicaltrials.gov/show/NCT00470587ADAPT: Australia
      New Zealand Clinical Trials Registry ACTRN12611001069943.

PMID- 28515107
TI  - A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D3
      Supplementation on Breast Density in Premenopausal Women.
AB  - Background: This double-blind, placebo-controlled parallel group trial assessed
      whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 over
      one year reduces percent mammographic breast density in premenopausal
      women.Methods: The trial was conducted between October 2012 and June 2015, among
      premenopausal female volunteers from Quebec City (Quebec, Canada). Women were
      randomized with ratio 1:1:1:1 to one of four study arms (1,000, 2,000, or 3,000
      IU/day vitamin D3 or placebo). The primary outcome was mean change in percent
      mammographic breast density. Participants and research team were blinded to study
      arm assignment.Results: Participants (n = 405) were randomized to receive 1,000
      (n = 101), 2,000 (n = 104), or 3,000 IU/day (n = 101) vitamin D3, or a placebo (n
      = 99). The primary analysis included 391 participants (96, 99, 100, and 96,
      respectively). After the one-year intervention, mean +/- SE change in percent
      breast density in the arms 1,000 IU/day (-5.5% +/- 0.5%) and 2,000 IU/day (-5.9%
      +/- 0.5%) vitamin D3 was similar to that in the placebo arm (-5.7% +/- 0.5%) (P
      values = 1.0). In the 3,000 IU/day vitamin D3 arm, percent breast density also
      declined but slightly less (-3.8% +/- 0.5%) compared with placebo arm (P = 0.03).
      Adherence to intervention was excellent (92.8%), and reporting of health problems
      was comparable among study arms (P >= 0.95). All participants had normal serum
      calcium.Conclusions: In premenopausal women, one-year supplementation with 1,000,
      2,000, or 3,000 IU/day vitamin D3 resulted in a reduction of percent breast
      density no greater than that seen with the placebo.Impact: At doses of 1,000
      3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk
      through changes in breast density. Cancer Epidemiol Biomarkers Prev; 26(8); 1233
      41. (c)2017 AACR.

PMID- 28515105
TI  - Free-Circulating Methylated DNA in Blood for Diagnosis, Staging, Prognosis, and
      Monitoring of Head and Neck Squamous Cell Carcinoma Patients: An Observational
      Prospective Cohort Study.
AB  - BACKGROUND: Circulating cell-free DNA methylation testing in blood has recently
      received regulatory approval for screening of colorectal cancer. Its application
      in other clinical settings, including staging, prognosis, prediction, and
      recurrence monitoring is highly promising, and of particular interest in head and
      neck squamous cell carcinomas (HNSCCs) that represent a heterogeneous group of
      cancers with unsatisfactory treatment guidelines. METHODS: Short stature homeobox
      2 (SHOX2) and septin 9 (SEPT9) DNA methylation in plasma from 649 prospectively
      enrolled patients (training study: 284 HNSCC/122 control patients; testing study:
      141 HNSCC/102 control patients) was quantified before treatment and
      longitudinally during surveillance. RESULTS: In the training study, 59% of HNSCC
      patients were methylation-positive at 96% specificity. Methylation levels
      correlated with tumor and nodal category (P < 0.001). Initially increased
      methylation levels were associated with a higher risk of death [SEPT9: hazard
      ratio (HR) = 5.27, P = 0.001; SHOX2: HR = 2.32, P = 0.024]. Disease
      recurrence/metastases were detected in 47% of patients up to 377 days earlier
      compared to current clinical practice. The onset of second cancers was detected
      up to 343 days earlier. In the testing study, sensitivity (52%), specificity
      (95%), prediction of overall survival (SEPT9: HR = 2.78, P = 0.022; SHOX2: HR =
      2.50, P = 0.026), and correlation with tumor and nodal category (P <0.001) were
      successfully validated. CONCLUSIONS: Methylation testing in plasma is a powerful
      diagnostic tool for molecular disease staging, risk stratification, and disease
      monitoring. Patients with initially high biomarker levels might benefit from
      intensified treatment and posttherapeutic surveillance. The early detection of a
      recurrent/metastatic disease or a second malignancy could lead to an earlier
      consecutive treatment, thereby improving patients' outcomes.

PMID- 28515109
TI  - Updated Review of Prevalence of Major Risk Factors and Use of Screening Tests for
      Cancer in the United States.
AB  - Much of the suffering and death from cancer could be prevented by more systematic
      efforts to reduce tobacco use and obesity, improve diet, and increase physical
      activity and use of established vaccines and screening tests. Monitoring the
      prevalence of cancer risk factors and preventive tests helps guide cancer
      prevention and early detection efforts. We provide an updated review, using data
      through 2015, of the prevalence of major risk factors, cancer screening, and
      vaccination for U.S. adults and youth. Cigarette smoking among adults decreased
      to 15.3% in 2015 but remains higher among lower socioeconomic persons (GED:
      34.1%, graduate degree: 3.7%), with considerable state variation (Utah: 9.1%,
      Kentucky: 26.0%). The prevalence of obesity among both adults (37.7%) and
      adolescents (20.6%) remains high, particularly among black women (57.2%), and
      ranges from 20.2% (Colorado) to 36.2% (Louisiana) among adults. Pap testing
      remains the most commonly utilized cancer screening test (81.4%). While
      colorectal cancer screening has increased, only 62.6% are up-to-date with
      recommendations. Cancer screening is lowest among the uninsured and varies across
      states. Despite some improvements, systematic efforts to further reduce the
      suffering and death from cancer should be enhanced. Continued investment in
      surveillance of cancer prevention and early detection metrics is also needed.
      Cancer Epidemiol Biomarkers Prev; 26(8); 1192-208. (c)2017 AACR.

PMID- 28515108
TI  - A Comparison of the Natural History of HPV Infection and Cervical Abnormalities
      among HIV-Positive and HIV-Negative Women in Senegal, Africa.
AB  - Background: There is evidence of an interaction between HIV and human
      papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer
      mortality among HIV-positive women. This study aims to determine how the natural
      history of cervical HPV infection differs by HIV status.Methods: A total of 1,320
      women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of
      two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub
      sample of histology) and HPV DNA testing were performed at approximately 4-month
      intervals yielding data from over 7,900 clinic visits. Competing risk modeling
      was used to estimate rates for transitioning between three clinically relevant
      natural history stages: Normal, HPV, and HSIL (high-grade squamous
      intraepithelial lesions). Among HIV-positive women, exploratory univariate
      analyses were conducted examining the impact of HPV type, infection with multiple
      HPV types, HIV type, CD4+ count, and age.Results: HIV-positive women had higher
      rates of progression and lower rates of regression compared with HIV-negative
      women (i.e., adverse transitions). HIV-positive women had a 2.55 [95% confidence
      interval (CI), 1.69-3.86; P < 0.0001] times higher rate of progression from HPV
      to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07,
      respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count
      <200/mm3 were associated with adverse transitions.Conclusions: Adverse HIV
      effects persist throughout HPV natural history stages.Impact: In the limited
      resource setting of sub-Saharan Africa where cervical cancer screening is not
      widely available, the high-risk population of HIV-positive women may be ideal for
      targeted screening. Cancer Epidemiol Biomarkers Prev; 26(6); 886-94. (c)2017
      AACR.

PMID- 28515110
TI  - Do Men and Women Need to Be Screened Differently with Fecal Immunochemical
      Testing? A Cost-Effectiveness Analysis.
AB  - Background: Several studies suggest that test characteristics for the fecal
      immunochemical test (FIT) differ by gender, triggering a debate on whether men
      and women should be screened differently. We used the microsimulation model
      MISCAN-Colon to evaluate whether screening stratified by gender is cost
      effective.Methods: We estimated gender-specific FIT characteristics based on
      first-round positivity and detection rates observed in a FIT screening pilot
      (CORERO-1). Subsequently, we used the model to estimate harms, benefits, and
      costs of 480 gender-specific FIT screening strategies and compared them with
      uniform screening.Results: Biennial FIT screening from ages 50 to 75 was less
      effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY)
      gained, respectively] at higher costs (?42,161 vs. -?5,471, respectively).
      However, the incremental QALYs gained and costs of annual screening compared with
      biennial screening were more similar for both genders (8.7 QALYs gained and
      ?26,394 for women vs. 6.7 QALYs gained and ?20,863 for men). Considering all
      evaluated screening strategies, optimal gender-based screening yielded at most 7%
      more QALYs gained than optimal uniform screening and even resulted in equal costs
      and QALYs gained from a willingness-to-pay threshold of ?1,300.Conclusions: FIT
      screening is less effective in women, but the incremental cost-effectiveness is
      similar in men and women. Consequently, screening stratified by gender is not
      more cost-effective than uniform FIT screening.Impact: Our conclusions support
      the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev;
      26(8); 1328-36. (c)2017 AACR.

PMID- 28515111
TI  - Racial Differences in Adjuvant Endocrine Therapy Use and Discontinuation in
      Association with Mortality among Medicare Breast Cancer Patients by Receptor
      Status.
AB  - Background: There are racial disparities in breast cancer mortality. Our purpose
      was to determine whether racial/ethnic differences in use and discontinuation of
      adjuvant endocrine therapy (AET) differed by hormone receptor status and whether
      discontinuation was associated with mortality.Methods: We conducted a
      retrospective cohort study with SEER/Medicare dataset of women age >=65 years
      diagnosed with stage I-III breast cancer in Medicare Part-D from 2007 to 2009,
      stratified by hormone receptor status. We performed multivariable logistic
      regressions to assess racial differences for the odds of AET initiation and Cox
      proportional hazards models to determine the risk of discontinuation and
      mortality.Results: Of 14,902 women, 64.5% initiated AET <12 months of diagnosis.
      Among those with hormone receptor-positive cancer, 74.8% initiated AET compared
      with 5.6% of women with negative and 54.0% with unknown-receptor status. Blacks
      were less likely to initiate [OR, 0.76; 95% confidence interval (CI), 0.66-0.88]
      compared with whites. However, those with hormone receptor-positive disease were
      less likely to discontinue (HR, 0.89; 95% CI, 0.80-0.98). Women who initiated
      with aromatase inhibitors had increased risk of discontinuation compared with
      women who initiated tamoxifen (HR, 1.12; 95% CI, 1.05-1.20). Discontinuation
      within 12 months was associated with higher risk of all-cause (HR, 1.75; 95% CI,
      1.74-2.00) and cancer-specific mortality (HR, 2.76; 95% CI, 1.74-4.38) after
      controlling for race/ethnicity.Conclusions: There are racial/ethnic differences
      in AET use and discontinuation. Discontinuing treatment was associated with
      higher risk of all-cause and cancer-specific mortality regardless of hormone
      receptor status.Impact: This study underscores the need to study factors that
      influence discontinuation and the survival benefits of receiving AET for hormone
      receptor-negative breast cancer. Cancer Epidemiol Biomarkers Prev; 26(8); 1266
      75. (c)2017 AACR.

PMID- 28515112
TI  - Impact of the Metabolic Syndrome on Mortality is Modified by Objective Short
      Sleep Duration.
AB  - BACKGROUND: To examine whether objective sleep duration is an effect modifier of
      the impact of metabolic syndrome (MetS) on all-cause and cardiovascular
      disease/cerebrovascular mortality. METHODS AND RESULTS: We addressed this
      question in the Penn State Adult Cohort, a random, general population sample of
      1344 men and women (48.8+/-14.2 years) who were studied in the sleep laboratory
      and followed up for 16.6+/-4.2 years. MetS was defined by the presence of 3 or
      more of obesity (>=30 kg/m2), elevated total cholesterol (>=200 mg/dL),
      triglycerides (>=150 mg/dL), fasting glucose (>=100 mg/dL), and blood pressure
      (>=130/85 mm Hg). Polysomnographic sleep duration was classified into clinically
      meaningful categories. Among the 1344 participants, 22.0% of them died during the
      follow-up. We tested the interaction between MetS and polysomnographic sleep
      duration on mortality using Cox proportional hazard models controlling for
      multiple potential confounders (P<0.05). The hazard ratios (95% CI) of all-cause
      and cardiovascular disease/cerebrovascular mortality associated with MetS were
      1.29 (0.89-1.87) and 1.49 (0.75-2.97) for individuals who slept >=6 hours and
      1.99 (1.53-2.59) and 2.10 (1.39-3.16) for individuals who slept <6 hours.
      Interestingly, this effect modification was primarily driven by the elevated
      blood pressure and glucose dysregulation components of MetS. CONCLUSIONS: The
      risk of mortality associated with MetS is increased in those with short sleep
      duration. Short sleep in individuals with MetS may be linked to greater central
      autonomic and metabolic dysfunction. Future clinical trials should examine
      whether lengthening sleep improves the prognosis of individuals with MetS.

PMID- 28515113
TI  - Force-Sensing Catheters During Pediatric Radiofrequency Ablation: The FEDERATION
      Study.
AB  - BACKGROUND: Based on data from studies of atrial fibrillation ablations, optimal
      parameters for the TactiCath (TC; St. Jude Medical, Inc) force-sensing ablation
      catheter are a contact force of 20 g and a force-time integral of 400 g.s for the
      creation of transmural lesions. We aimed to evaluate TC in pediatric and
      congenital heart disease patients undergoing ablation. METHODS AND RESULTS:
      Comprehensive chart and case reviews were performed from June 2015 to March 2016.
      Of the 102 patients undergoing electrophysiology study plus ablation, 58 (57%)
      underwent ablation initially with a force-sensing catheter. Patients had an
      average age of 14 (2.4-23) years and weight of 58 (18-195) kg with 15 patients
      having abnormal cardiac anatomy. Electrophysiology diagnoses for the +TC group
      included 30 accessory pathway-mediated tachycardia, 24 atrioventricular nodal
      reentrant tachycardia, and 7 other. Baseline generator settings included a power
      of 20 W, temperature of 40 degrees , and 6 cc/min flow during lesion creation
      with 11 patients (19%) having alterations to parameters. Seventeen patients (30%)
      converted to an alternate ablation source. A total of 516 lesions were performed
      using the TC with a median contact force of 6 g, force-time integral of 149 g.s,
      and lesion size index of 3.3. Median-term follow-up demonstrated 5 (10%)
      recurrences with no acute or median-term complications. CONCLUSIONS: TactiCath
      can be effectively employed in the treatment of pediatric patients with
      congenital heart disease with lower forces than previously described in the
      atrial fibrillation literature. Patients with atrioventricular nodal reentrant
      tachycardia or atrioventricular reciprocating tachycardia may not require
      transmural lesions and the TC may provide surrogate markers for success during
      slow pathway ablation.

PMID- 28515114
TI  - Cardiopulmonary Resuscitation Training Disparities in the United States.
AB  - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is associated with
      increased survival from cardiac arrest, yet bystander CPR rates are low in many
      communities. The overall prevalence of CPR training in the United States and
      associated individual-level disparities are unknown. We sought to measure the
      national prevalence of CPR training and hypothesized that older age and lower
      socioeconomic status would be independently associated with a lower likelihood of
      CPR training. METHODS AND RESULTS: We administered a cross-sectional telephone
      survey to a nationally representative adult sample. We assessed the demographics
      of individuals trained in CPR within 2 years (currently trained) and those who
      had been trained in CPR at some point in time (ever trained). The association of
      CPR training and demographic variables were tested using survey weighted logistic
      regression. Between September 2015 and November 2015, 9022 individuals completed
      the survey; 18% reported being currently trained in CPR, and 65% reported
      training at some point previously. For each year of increased age, the likelihood
      of being currently CPR trained or ever trained decreased (currently trained: odds
      ratio, 0.98; 95% CI, 0.97-0.99; P<0.01; ever trained: OR, 0.99; 95% CI, 0.98
      0.99; P=0.04). Furthermore, there was a greater then 4-fold difference in odds of
      being currently CPR trained from the 30-39 to 70-79 year old age groups (95% CI,
      0.10-0.23). Factors associated with a lower likelihood of CPR training were
      lesser educational attainment and lower household income (P<0.01 for each of
      these variables). CONCLUSIONS: A minority of respondents reported current
      training in CPR. Older age, lesser education, and lower income were associated
      with reduced likelihood of CPR training. These findings illustrate important gaps
      in US CPR education and suggest the need to develop tailored CPR training efforts
      to address this variability.

PMID- 28515115
TI  - Impact of Antihypertensive Treatment on Maternal and Perinatal Outcomes in
      Pregnancy Complicated by Chronic Hypertension: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Chronic hypertension complicates around 3% of all pregnancies. There
      is evidence that treating severe hypertension reduces maternal morbidity. This
      study aimed to systematically review randomized controlled trials of
      antihypertensive agents treating chronic hypertension in pregnancy to determine
      the effect of this intervention. METHODS AND RESULTS: Medline (via OVID), Embase
      (via OVID) and the Cochrane Trials Register were searched from their earliest
      entries until November 30, 2016. All randomized controlled trials evaluating
      antihypertensive treatments for chronic hypertension in pregnancy were included.
      Data were extracted and analyzed in Stata (version 14.1). Fifteen randomized
      controlled trials (1166 women) were identified for meta-analysis. A clinically
      important reduction in the incidence of severe hypertension was seen with
      antihypertensive treatment versus no antihypertensive treatment/placebo (5
      studies, 446 women; risk ratio 0.33, 95%CI 0.19-0.56; I2 0.0%). There was no
      difference in the incidence of superimposed pre-eclampsia (7 studies, 727 women;
      risk ratio 0.74, 95%CI 0.49-1.11; I2 28.1%), stillbirth/neonatal death (4
      studies, 667 women; risk ratio 0.37, 95%CI 0.11-1.26; I2 0.0%), birth weight (7
      studies, 802 women; weighted mean difference -60 g, 95%CI -200 to 80 g; I2 0.0%),
      or small for gestational age (4 studies, 369 women; risk ratio 1.01, 95%CI 0.53
      1.94; I2 0.0%) with antihypertensive treatment versus no treatment/placebo.
      CONCLUSIONS: Antihypertensive treatment reduces the risk of severe hypertension
      in pregnant women with chronic hypertension. A considerable paucity of data
      exists to guide choice of antihypertensive agent. Adequately powered head-to-head
      randomized controlled trials of commonly used antihypertensive agents are
      required to inform prescribing.

PMID- 28515117
TI  - Venous Thromboembolism Risk With Antidepressants: Driven by Disease or Drugs?

PMID- 28515116
TI  - Antidepressants, Depression, and Venous Thromboembolism Risk: Large Prospective
      Study of UK Women.
AB  - BACKGROUND: Some investigators have reported an excess risk of venous
      thromboembolism (VTE) associated with depression and with use of antidepressant
      drugs. We explored these associations in a large prospective study of UK women.
      METHODS AND RESULTS: The Million Women Study recruited 1.3 million women through
      the National Health Service Breast Screening Programme in England and Scotland.
      Three years after recruitment, women were sent a second questionnaire that
      enquired about depression and regular use of medications in the previous 4 weeks.
      The present analysis included those who responded and did not have prior VTE,
      cancer, or recent surgery. Follow-up for VTE was through linkage to routinely
      collected National Health Service statistics. Cox regression analyses yielded
      adjusted hazard ratios and 95% CIs. A total of 734 092 women (mean age 59.9
      years) were included in the analysis; 6.9% reported use of antidepressants, 2.7%
      reported use of other psychotropic drugs, and 1.8% reported being treated for
      depression or anxiety but not use of psychotropic drugs. During follow-up for an
      average of 7.3 years, 3922 women were hospitalized for and/or died from VTE.
      Women who reported antidepressant use had a significantly higher risk of VTE than
      women who reported neither depression nor use of psychotropic drugs (hazard
      ratio, 1.39; 95% CI, 1.23-1.56). VTE risk was not significantly increased in
      women who reported being treated for depression or anxiety but no use of
      antidepressants or other psychotropic drugs (hazard ratio, 1.19; 95% CI, 0.95
      1.49). CONCLUSIONS: Use of antidepressants is common in UK women and is
      associated with an increased risk of VTE.

PMID- 28515118
TI  - Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC
      (Chronic Renal Insufficiency Cohort) Study.
AB  - BACKGROUND: Heart failure is common in patients with chronic kidney disease. We
      studied risk factors for incident heart failure among 3557 participants in the
      CRIC (Chronic Renal Insufficiency Cohort) Study. METHODS AND RESULTS: Kidney
      function was assessed by estimated glomerular filtration rate (eGFR) using serum
      creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an
      average of 6.3 years of follow-up, 452 participants developed incident heart
      failure. After adjustment for age, sex, race, and clinical site, hazard ratio
      (95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was
      1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1
      SD higher log-albuminuria was 1.65 (1.53, 1.78), all P<0.001. When all 3 kidney
      function measures were simultaneously included in the model, lower cystatin C
      based eGFR and higher log-albuminuria remained significantly and directly
      associated with incidence of heart failure. After adjusting for eGFR,
      albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95%
      CI 1.09, 1.72, P=0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P=0.006),
      hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P<0.001), interleukin-6 (1.15, 95% CI
      1.05, 1.25, P=0.002), and tumor necrosis factor-alpha (1.10, 95% CI 1.00, 1.21,
      P=0.05) were all significantly and directly associated with incidence of heart
      failure. CONCLUSIONS: Our study indicates that cystatin C-based eGFR and
      albuminuria are better predictors for risk of heart failure compared to
      creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and
      poor glycemic control are independent risk factors for the development of heart
      failure among patients with chronic kidney disease.

PMID- 28515119
TI  - Pulse Wave Velocity Predicts Response to Renal Denervation in Isolated Systolic
      Hypertension.
AB  - BACKGROUND: Renal sympathetic denervation seems to be less effective as a
      treatment for hypertension in patients with isolated systolic hypertension, a
      condition associated with elevated central arterial stiffness. Because isolated
      systolic hypertension can also be caused by wave reflection or increased cardiac
      output, a more differentiated approach might improve patient preselection for
      renal sympathetic denervation. We sought to evaluate the additional predictive
      value of invasive pulse wave velocity for response to renal sympathetic
      denervation in patients with combined versus isolated systolic hypertension.
      METHODS AND RESULTS: Patients scheduled for renal sympathetic denervation
      underwent additional invasive measurement of pulse wave velocity and pulse
      pressure before denervation. Blood pressure was assessed via ambulatory
      measurement at baseline and after 3 months. In total 109 patients (40 patients
      with isolated systolic hypertension) were included in our analysis. After 3
      months, blood pressure reduction was more pronounced among patients with combined
      hypertension compared with patients with isolated systolic hypertension (systolic
      24-hour average 9.3+/-10.5 versus 5.0+/-11.5 mm Hg, P=0.046). However, when
      stratifying patients with isolated systolic hypertension by invasive pulse wave
      velocity, patients in the lowest tertile of pulse wave velocity had comparable
      blood pressure reduction (12.1+/-12.6 mm Hg, P=0.006) despite lower baseline
      blood pressure than patients with combined hypertension (systolic 24-hour average
      154.8+/-12.5 mm Hg in combined hypertension versus 141.2+/-8.1, 148.4+/-10.9, and
      150.5+/-12.7 mm Hg, respectively, by tertiles of pulse wave velocity, P=0.002).
      CONCLUSIONS: Extended assessment of arterial stiffness can help improve patient
      preselection for renal sympathetic denervation and identify a subgroup of
      isolated systolic hypertension patients who benefit from sympathetic modulation.

PMID- 28515122
TI  - Sixty seconds on . . . pagers.

PMID- 28515120
TI  - Remote Ischemic Perconditioning to Reduce Reperfusion Injury During Acute ST
      Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Remote ischemic conditioning (RIC) is a noninvasive therapeutic
      strategy that uses brief cycles of blood pressure cuff inflation and deflation to
      protect the myocardium against ischemia-reperfusion injury. The objective of this
      systematic review was to determine the impact of RIC on myocardial salvage index,
      infarct size, and major adverse cardiovascular events when initiated before
      catheterization. METHODS AND RESULTS: Electronic searches of Medline, Embase, and
      Cochrane Central Register of Controlled Trials were conducted and reference lists
      were hand searched. Randomized controlled trials comparing percutaneous coronary
      intervention (PCI) with and without RIC for patients with ST-segment-elevation
      myocardial infarction were included. Two reviewers independently screened
      abstracts, assessed quality of the studies, and extracted data. Data were pooled
      using random-effects models and reported as mean differences and relative risk
      with 95% confidence intervals. Eleven articles (9 randomized controlled trials)
      were included with a total of 1220 patients (RIC+PCI=643, PCI=577). Studies with
      no events were excluded from meta-analysis. The myocardial salvage index was
      higher in the RIC+PCI group compared with the PCI group (mean difference: 0.08;
      95% confidence interval, 0.02-0.14). Infarct size was reduced in the RIC+PCI
      group compared with the PCI group (mean difference: -2.46; 95% confidence
      interval, -4.66 to -0.26). Major adverse cardiovascular events were lower in the
      RIC+PCI group (9.5%) compared with the PCI group (17.0%; relative risk: 0.57; 95%
      confidence interval, 0.40-0.82). CONCLUSIONS: RIC appears to be a promising
      adjunctive treatment to PCI for the prevention of reperfusion injury in patients
      with ST-segment-elevation myocardial infarction; however, additional high-quality
      research is required before a change in practice can be considered.

PMID- 28515125
TI  - Britain without the EMA.

PMID- 28515124
TI  - Your vote counts: how will a soft or hard Brexit affect health?

PMID- 28515123
TI  - All-Trans Retinoic Acid Prevents Osteosarcoma Metastasis by Inhibiting M2
      Polarization of Tumor-Associated Macrophages.
AB  - M2-polarized tumor-associated macrophages (TAM) play a critical role in cancer
      invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis
      of K7M2 WT osteosarcoma cells to the lungs in mice, thus establishing M2 TAMs as
      a therapeutic target for blocking osteosarcoma metastasis. We found that all
      trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the
      M2 polarization of TAMs. ATRA suppressed IL13- or IL4-induced M2-type
      macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2
      type macrophages in vitro ATRA reduced the number of pulmonary metastatic nodes
      of osteosarcoma and decreased expression of M2-type macrophages in metastatic
      nodes both in intravenous injection and orthotopic transplantation models. ATRA's
      effect was independent of conventional STAT3/6 or C/EBPbeta signaling, which
      regulate M2-like polarization of macrophages. Quantitative genomic and functional
      analyses revealed that MMP12, a macrophage-secreted elastase, was elevated in
      IL13-skewed TAM polarization, whereas ATRA treatment downregulated IL13-induced
      secretion of MMP12. This downregulation correlates with the antimetastasis effect
      of ATRA. Our results show the role of TAM polarization in osteosarcoma
      metastasis, identify a therapeutic opportunity for antimetastasis treatment, and
      indicate ATRA treatment as an approach for preventing osteosarcoma metastasis via
      M2-type polarization intervention. Cancer Immunol Res; 5(7); 547-59. (c)2017
      AACR.

PMID- 28515127
TI  - A retrospective analysis of mitral valve pathology in the setting of bicuspid
      aortic valves.
AB  - The therapeutic implications of bicuspid aortic valve associations have come
      under scrutiny in the transcatheter aortic valve implantation era. We evaluate
      the spectrum of mitral valve disease in patients with bicuspid aortic valves to
      determine the need for closer echocardiographic scrutiny/follow-up of the mitral
      valve. A retrospective analysis of echocardiograms done at a referral hospital
      over five years was conducted in patients with bicuspid aortic valves with
      special attention to congenital abnormalities of the mitral valve. One hundred
      and forty patients with a bicuspid aortic valve were included. A congenital
      mitral valve abnormality was present in eight (5.7%, P = 0.01) with a parachute
      mitral valve in four (2.8%), an accessory mitral valve leaflet in one (0.7%),
      mitral valve prolapse in one, a cleft in one and the novel finding of a
      trileaflet mitral valve in one. Minor abnormalities included an elongated
      anterior mitral valve leaflet (P < 0.001), the increased incidence of
      physiological mitral regurgitation (P < 0.001), abnormal papillary muscles (P =
      0.002) and an additional chord or tendon in the left ventricle cavity (P =
      0.007). Mitral valve abnormalities occur more commonly in patients with bicuspid
      aortic valves than matched healthy individuals. The study confirms that
      abnormalities in these patients extend beyond the aorta. These abnormalities did
      not have a significant functional effect.

PMID- 28515121
TI  - AMPKalpha1-LDH pathway regulates muscle stem cell self-renewal by controlling
      metabolic homeostasis.
AB  - Control of stem cell fate to either enter terminal differentiation versus
      returning to quiescence (self-renewal) is crucial for tissue repair. Here, we
      showed that AMP-activated protein kinase (AMPK), the master metabolic regulator
      of the cell, controls muscle stem cell (MuSC) self-renewal. AMPKalpha1-/- MuSCs
      displayed a high self-renewal rate, which impairs muscle regeneration. AMPKalpha1
      /- MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis.
      We identified lactate dehydrogenase (LDH) as a new functional target of
      AMPKalpha1. LDH, which is a non-limiting enzyme of glycolysis in differentiated
      cells, was tightly regulated in stem cells. In functional experiments, LDH
      overexpression phenocopied AMPKalpha1-/- phenotype, that is shifted MuSC
      metabolism toward glycolysis triggering their return to quiescence, while
      inhibition of LDH activity rescued AMPKalpha1-/- MuSC self-renewal. Finally,
      providing specific nutrients (galactose/glucose) to MuSCs directly controlled
      their fate through the AMPKalpha1/LDH pathway, emphasizing the importance of
      metabolism in stem cell fate.

PMID- 28515128
TI  - Correction for Iwasaki et al., "Homolactic Acid Fermentation by the Genetically
      Engineered Thermophilic Homoacetogen Moorella thermoacetica ATCC 39073".

PMID- 28515126
TI  - Radiomanganese PET Detects Changes in Functional beta-Cell Mass in Mouse Models
      of Diabetes.
AB  - The noninvasive measurement of functional beta-cell mass would be clinically
      valuable for monitoring the progression of type 1 and type 2 diabetes as well as
      the viability of transplanted insulin-producing cells. Although previous work
      using MRI has shown promise for functional beta-cell mass determination through
      voltage-dependent Ca2+ channel (VDCC)-mediated internalization of Mn2+, the
      clinical utility of this technique is limited by the cytotoxic levels of the Mn2+
      contrast agent. Here, we show that positron emission tomography (PET) is
      advantageous for determining functional beta-cell mass using 52Mn2+ (t1/2: 5.6
      days). We investigated the whole-body distribution of 52Mn2+ in healthy adult
      mice by dynamic and static PET imaging. Pancreatic VDCC uptake of 52Mn2+ was
      successfully manipulated pharmacologically in vitro and in vivo using glucose,
      nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (KATP
      channel blockers), and diazoxide (KATP channel opener). In a mouse model of
      streptozotocin-induced type 1 diabetes, 52Mn2+ uptake in the pancreas was
      distinguished from healthy controls in parallel with classic histological
      quantification of beta-cell mass from pancreatic sections. 52Mn2+-PET also
      reported the expected increase in functional beta-cell mass in the ob/ob model of
      pretype 2 diabetes, a result corroborated by histological beta-cell mass
      measurements and live-cell imaging of beta-cell Ca2+ oscillations. These results
      indicate that 52Mn2+-PET is a sensitive new tool for the noninvasive assessment
      of functional beta-cell mass.

PMID- 28515130
TI  - Erratum for Pandey et al., "Intracellular pH Response to Weak Acid Stress in
      Individual Vegetative Bacillus subtilis Cells".

PMID- 28515131
TI  - Exenatide Improves HDL Particle Counts and Size Distribution in Patients With
      Long-standing Type 1 Diabetes.

PMID- 28515132
TI  - Inclusion of emergency department patients in early stages of sepsis in a quality
      improvement programme has the potential to improve survival: a prospective dual
      centre study.
AB  - STUDY OBJECTIVE: Sepsis quality improvement programmes typically focus on severe
      sepsis (ie, with acute organ failure). However, quality of ED care might be
      improved if these programmes included patients whose progression to severe sepsis
      could still be prevented (ie, infection without acute organ failure). We compared
      the impact on mortality of implementing a quality improvement programme among ED
      patients with a suspected infection with or without acute organ failure. METHODS:
      This prospective observational study among ED patients hospitalised with
      suspected infection was conducted in two hospitals in the Netherlands. After
      stratification by sepsis category (with or without organ failure), in-hospital
      mortality was compared between a full compliance (all quality performance
      measures achieved) and an incomplete compliance group. Multivariable logistic
      regression analysis was used to quantify the impact of full compliance on in
      hospital mortality, adjusting for disease severity, disposition and hospital.
      RESULTS: There were 1732 ED patients and 130 deaths. Full compliance was
      independently associated with approximately two-thirds reduction in the odds of
      hospital mortality (adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar
      in patients with and without organ failure. Among the 1379 patients with
      suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%)
      in the full compliance group and 49 (3.6%) in the incomplete compliance group
      (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ
      failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54
      (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI
      8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and
      incomplete compliance groups, and 34 (45%) who benefited were those without acute
      organ failure. CONCLUSIONS: Sepsis quality improvement programmes should
      incorporate ED patients in earlier stages of sepsis given the potential to reduce
      in-hospital mortality among this population.

PMID- 28515133
TI  - Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the
      Immature Form of Alphavirus.
AB  - Virus-like particles (VLPs) are noninfectious multiprotein structures that are
      engineered to self-assemble from viral structural proteins. Here, we developed a
      novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We
      identified two regions within the envelope protein, a structural component of
      chikungunya, where foreign antigens can be inserted without compromising VLP
      structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP
      surface in a highly symmetric manner and is thus capable of inducing strong
      immune responses against any inserted antigen. Furthermore, by mimicking the
      structure of the immature form of the virus, we altered our VLP's in vivo
      dynamics and enhanced its immunogenicity. We used the circumsporozoite protein
      (CSP) of the Plasmodium falciparum malaria parasite as an antigen and
      demonstrated that our VLP-based vaccine elicits strong immune responses against
      CSP in animals. The sera from immunized monkeys protected mice from malaria
      infection. Likewise, mice vaccinated with P. yoelii CSP-containing VLPs were
      protected from an infectious sporozoite challenge. Hence, our uniquely engineered
      VLP platform can serve as a blueprint for the development of vaccines against
      other pathogens and diseases.

PMID- 28515134
TI  - Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using
      the Mycobacterium tuberculosis Protein Array.
AB  - Johne's disease, a chronic gastrointestinal inflammatory disease caused by
      Mycobacterium avium subspecies paratuberculosis, is endemic in dairy cattle and
      other ruminants worldwide and remains a challenge to diagnose using traditional
      serological methods. Given the close phylogenetic relationship between M. avium
      subsp. paratuberculosis and the human pathogen Mycobacterium tuberculosis, here,
      we applied a whole-proteome M. tuberculosis protein array to identify
      seroreactive and diagnostic M. avium subsp. paratuberculosis antigens. A genome
      scale pairwise analysis of amino acid identity levels between orthologous
      proteins in M. avium subsp. paratuberculosis and M. tuberculosis showed an
      average of 62% identity, with more than half the orthologous proteins sharing
      >75% identity. Analysis of the M. tuberculosis protein array probed with sera
      from M. avium subsp. paratuberculosis-infected cattle showed antibody binding to
      729 M. tuberculosis proteins, with 58% of them having >=70% identity to M. avium
      subsp. paratuberculosis orthologs. The results showed that only 4 of the top 40
      seroreactive M. tuberculosis antigens were orthologs of previously reported M.
      avium subsp. paratuberculosis antigens, revealing the existence of a large number
      of previously unrecognized candidate diagnostic antigens. Enzyme-linked
      immunosorbent assay (ELISA) testing of 20 M. avium subsp. paratuberculosis
      recombinant proteins, representing reactive and nonreactive M. tuberculosis
      orthologs, further confirmed that the M. tuberculosis array has utility as a
      screening tool for identifying candidate antigens for Johne's disease
      diagnostics. Additional ELISA testing of field serum samples collected from dairy
      herds around the United States revealed that MAP2942c had the strongest
      seroreactivity with Johne's disease-positive samples. Collectively, our studies
      have considerably expanded the number of candidate M. avium subsp.
      paratuberculosis proteins with potential utility in the next generation of
      rationally designed Johne's disease diagnostic assays.

PMID- 28515135
TI  - Not All Antigens Are Created Equally: Progress, Challenges, and Lessons
      Associated with Developing a Vaccine for Leishmaniasis.
AB  - From experimental models and the analyses of patients, it is well documented that
      antigen-specific T cells are critical for protection against Leishmania
      infection. Effective vaccines require both targeting to the pathogen and an
      immune stimulant to induce maturation of appropriate immune responses. While a
      great number of antigens have been examined as vaccine candidates against various
      Leishmania species, few have advanced to human or canine clinical trials. With
      emphasis on antigen expression, in this minireview we discuss some of the vaccine
      platforms that are currently being explored for the development of Leishmania
      vaccines. It is clear that the vaccine platform of choice can have a significant
      impact upon the level of protection induced by particular antigens, and we
      provide and highlight some examples for which the vaccine system used has
      impacted the protective efficacy imparted.

PMID- 28515136
TI  - Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during
      Current or Convalescent Plasmodium falciparum Infection in Malawian Children.
AB  - Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with
      Plasmodium falciparum infections, but the immunologic basis for this linkage is
      poorly understood. We hypothesized that P. falciparum infection compromises the
      humoral and cellular immunity of the host to NTS, which increases the
      susceptibility of the host to iNTS infection. We prospectively recruited children
      aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi,
      and allocated them to the following groups; febrile with uncomplicated malaria,
      febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella
      enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole
      blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil
      respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S
      Typhimurium were reduced in febrile P. falciparum-infected children (median, 
      0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile
      malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], P = 0.052). In
      relation to SBA, C3 deposition on S Typhimurium was significantly reduced in
      febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared
      to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P =
      0.048). WBBA with respect to S Typhimurium was significantly reduced in febrile
      P. falciparum-infected children (median, 0.25 log10 [IQR, -0.73, 1.13], P =
      0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10
      [IQR, -1.68, -0.16]). In relation to WBBA, S Typhimurium-specific NRBA was
      reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20],
      P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR,
      33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S
      Typhimurium in children during malaria episodes, which may explain the increased
      risk of iNTS observed in children from settings of malaria endemicity. The
      mechanisms underlying humoral immunity impairment are incompletely understood and
      should be explored further.

PMID- 28515137
TI  - Under the influence: examination of prevalence and correlates of alcohol and
      marijuana consumption in relation to youth driving and passenger behaviours in
      Canada. A cross-sectional study.
AB  - BACKGROUND: Consequences of alcohol- and drug-impaired driving affect youth
      disproportionately. We describe individual- and area-level characteristics
      associated with risky driving and passenger behaviours among grade 9-12 students
      in Canada. METHODS: The 2014-2015 Canadian Student Tobacco, Alcohol and Drug
      Survey was administered to 24 650 students in provincially generalizable samples.
      Dichotomous outcomes included ever and last-30-day driving after drinking
      alcohol, ever and last-30-day driving after using marijuana, and ever and last-30
      day reporting of being a passenger with a driver who had been drinking or using
      marijuana. RESULTS: A total of 9.1% (99% confidence interval 7.9-10.3) of grade
      11-12 students reported ever driving after drinking, and 9.4% (99% confidence
      interval 8.3-10.4) reported ever driving after using marijuana. Almost half (48%)
      of grade 11-12 students reported ever participating in any risky driving or
      passenger behaviour. Over one-third (35%) of grade 9-12 students reported ever
      riding with a driver who had been drinking, and 20% reported ever riding with a
      driver who had been using marijuana. Logistic regression models showed that boys
      had higher odds of risky driving behaviours relative to girls, whereas girls had
      higher odds of risky passenger behaviours relative to boys. Students from rural
      schools had higher odds of drinking and driving and of riding with a driver who
      had drunk relative to students from urban schools. There were significant
      differences in risky driving and passenger behaviours by province.
      INTERPRETATION: A substantial number of Canadian youth reported risky driving and
      passenger behaviours, which varied by individual and area-level characteristics.
      Federal marijuana policy should aim to reduce the prevalence of drug-impaired
      driving. Additional provincial policies to prevent impaired driving are needed.

PMID- 28515138
TI  - Dalcetrapib and anacetrapib differently impact HDL structure and function in
      rabbits and monkeys.
AB  - Inhibition of cholesteryl ester transfer protein (CETP) increases HDL cholesterol
      (HDL-C) levels. However, the circulating CETP level varies and the impact of its
      inhibition in species with high CETP levels on HDL structure and function remains
      poorly characterized. This study investigated the effects of dalcetrapib and
      anacetrapib, the two CETP inhibitors (CETPis) currently being tested in large
      clinical outcome trials, on HDL particle subclass distribution and cholesterol
      efflux capacity of serum in rabbits and monkeys. New Zealand White rabbits and
      vervet monkeys received dalcetrapib and anacetrapib. In rabbits, CETPis increased
      HDL-C, raised small and large alpha-migrating HDL, and increased ABCA1-induced
      cholesterol efflux. In vervet monkeys, although anacetrapib produced similar
      results, dalcetrapib caused opposite effects because the LDL-C level was
      increased by 42% and HDL-C decreased by 48% (P < 0.01). The levels of alpha- and
      prebeta-HDL were reduced by 16% (P < 0.001) and 69% (P < 0.01), resulting in a
      decrease of the serum cholesterol efflux capacity. CETPis modulate the plasma
      levels of mature and small HDL in vivo and consequently the cholesterol efflux
      capacity. The opposite effects of dalcetrapib in different species indicate that
      its impact on HDL metabolism could vary greatly according to the metabolic
      environment.

PMID- 28515139
TI  - Changes in ceramide metabolism are essential in Madin-Darby canine kidney cell
      differentiation.
AB  - Ceramides (Cers) and complex sphingolipids with defined acyl chain lengths play
      important roles in numerous cell processes. Six Cer synthase (CerS) isoenzymes
      (CerS1-6) are the key enzymes responsible for the production of the diversity of
      molecular species. In this study, we investigated the changes in sphingolipid
      metabolism during the differentiation of Madin-Darby canine kidney (MDCK) cells.
      By MALDI TOF TOF MS, we analyzed the molecular species of Cer, glucosylceramide
      (GlcCer), lactosylceramide (LacCer), and SM in nondifferentiated and
      differentiated cells (cultured under hypertonicity). The molecular species
      detected were the same, but cells subjected to hypertonicity presented higher
      levels of C24:1 Cer, C24:1 GlcCer, C24:1 SM, and C16:0 LacCer. Consistently with
      the molecular species, MDCK cells expressed CerS2, CerS4, and CerS6, but with no
      differences during cell differentiation. We next evaluated the different
      synthesis pathways with sphingolipid inhibitors and found that cells subjected to
      hypertonicity in the presence of amitriptyline, an inhibitor of acid
      sphingomyelinase, showed decreased radiolabeled incorporation in LacCer and cells
      did not develop a mature apical membrane. These results suggest that
      hypertonicity induces the endolysosomal degradation of SM, generating the Cer
      used as substrate for the synthesis of specific molecular species of
      glycosphingolipids that are essential for MDCK cell differentiation.

PMID- 28515140
TI  - Three-Year Impacts Of The Affordable Care Act: Improved Medical Care And Health
      Among Low-Income Adults.
AB  - Major policy uncertainty continues to surround the Affordable Care Act (ACA) at
      both the state and federal levels. We assessed changes in health care use and
      self-reported health after three years of the ACA's coverage expansion, using
      survey data collected from low-income adults through the end of 2016 in three
      states: Kentucky, which expanded Medicaid; Arkansas, which expanded private
      insurance to low-income adults using the federal Marketplace; and Texas, which
      did not expand coverage. We used a difference-in-differences model with a control
      group and an instrumental variables model to provide individual-level estimates
      of the effects of gaining insurance. By the end of 2016 the uninsurance rate in
      the two expansion states had dropped by more than 20 percentage points relative
      to the nonexpansion state. For uninsured people gaining coverage, this change was
      associated with a 41-percentage-point increase in having a usual source of care,
      a $337 reduction in annual out-of-pocket spending, significant increases in
      preventive health visits and glucose testing, and a 23-percentage-point increase
      in "excellent" self-reported health. Among adults with chronic conditions, we
      found improvements in affordability of care, regular care for those conditions,
      medication adherence, and self-reported health.

PMID- 28515141
TI  - Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism.
AB  - Hormonal signals help to maintain glucose and lipid homeostasis in the liver
      during the periods of fasting. Glucagon, a pancreas-derived hormone induced by
      fasting, promotes gluconeogenesis through induction of intracellular cAMP
      production. Glucagon also stimulates hepatic fatty acid oxidation but the
      underlying mechanism is poorly characterized. Here we report that following the
      acute induction of gluconeogenic genes Glucose 6 phosphatase (G6Pase) and
      Phosphoenolpyruvate carboxykinase (Pepck) expression through cAMP-response
      element-binding protein (CREB), glucagon triggers a second delayed phase of fatty
      acid oxidation genes Acyl-coenzyme A oxidase (Aox) and Carnitine
      palmitoyltransferase 1a (Cpt1a) expression via extracellular cAMP. Increase in
      extracellular cAMP promotes PPARalpha activity through direct phosphorylation by
      AMP-activated protein kinase (AMPK), while inhibition of cAMP efflux greatly
      attenuates Aox and Cpt1a expression. Importantly, cAMP injection improves lipid
      homeostasis in fasted mice and obese mice, while inhibition of cAMP efflux
      deteriorates hepatic steatosis in fasted mice. Collectively, our results
      demonstrate the vital role of glucagon-stimulated extracellular cAMP in the
      regulation of hepatic lipid metabolism through AMPK-mediated PPARalpha
      activation. Therefore, strategies to improve cAMP efflux could serve as potential
      new tools to prevent obesity-associated hepatic steatosis.

PMID- 28515142
TI  - Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold
      protein to polarize active Rac1 distribution.
AB  - Endothelial cells line the lumen of the vessel wall and are exposed to flow. In
      linear parts of the vessel, the endothelial cells experience laminar flow,
      resulting in endothelial cell alignment in the direction of flow, thereby
      protecting the vessel wall from inflammation and permeability. In order for
      endothelial cells to align, they undergo rapid remodeling of the actin
      cytoskeleton by local activation of the small GTPase Rac1. However, it is not
      clear whether sustained and local activation of Rac1 is required for long-term
      flow-induced cell alignment. Using a FRET-based DORA Rac1 biosensor, we show that
      local Rac1 activity remains for 12 h upon long-term flow. Silencing studies show
      that the RhoGEF Trio is crucial for keeping active Rac1 at the downstream side of
      the cell and, as a result, for long-term flow-induced cell alignment.
      Surprisingly, Trio appears to be not involved in flow-induced activation of Rac1.
      Our data show that flow induces Rac1 activity at the downstream side of the cell
      in a Trio-dependent manner and that Trio functions as a scaffold protein rather
      than a functional GEF under long-term flow conditions.

PMID- 28515143
TI  - Cyclin C influences the timing of mitosis in fission yeast.
AB  - The multiprotein Mediator complex is required for the regulated transcription of
      nearly all RNA polymerase II-dependent genes. Mediator contains the Cdk8
      regulatory subcomplex, which directs periodic transcription and influences cell
      cycle progression in fission yeast. Here we investigate the role of CycC, the
      cognate cyclin partner of Cdk8, in cell cycle control. Previous reports suggested
      that CycC interacts with other cellular Cdks, but a fusion of CycC to Cdk8
      reported here did not cause any obvious cell cycle phenotypes. We find that Cdk8
      and CycC interactions are stabilized within the Mediator complex and the activity
      of Cdk8-CycC is regulated by other Mediator components. Analysis of a mutant
      yeast strain reveals that CycC, together with Cdk8, primarily affects M-phase
      progression but mutations that release Cdk8 from CycC control also affect timing
      of entry into S phase.

PMID- 28515144
TI  - Transient activation of fission yeast AMPK is required for cell proliferation
      during osmotic stress.
AB  - The heterotrimeric kinase AMPK acts as an energy sensor to coordinate cell
      metabolism with environmental status in species from yeast through humans. Low
      intracellular ATP leads to AMPK activation through phosphorylation of the
      activation loop within the catalytic subunit. Other environmental stresses also
      activate AMPK, but it is unclear whether cellular energy status affects AMPK
      activation under these conditions. Fission yeast AMPK catalytic subunit Ssp2 is
      phosphorylated at Thr-189 by the upstream kinase Ssp1 in low-glucose conditions,
      similar to other systems. Here we find that hyperosmotic stress induces strong
      phosphorylation of Ssp2-T189 by Ssp1. Ssp2-pT189 during osmotic stress is
      transient and leads to transient regulation of AMPK targets, unlike sustained
      activation by low glucose. Cells lacking this activation mechanism fail to
      proliferate after hyperosmotic stress. Activation during osmotic stress requires
      energy sensing by AMPK heterotrimer, and osmotic stress leads to decreased
      intracellular ATP levels. We observed mitochondrial fission during osmotic
      stress, but blocking fission did not affect AMPK activation. Stress-activated
      kinases Sty1 and Pmk1 did not promote AMPK activation but contributed to
      subsequent inactivation. Our results show that osmotic stress induces transient
      energy stress, and AMPK activation allows cells to manage this energy stress for
      proliferation in new osmotic states.

PMID- 28515145
TI  - Target RNA Secondary Structure Is a Major Determinant of miR159 Efficacy.
AB  - In plants, microRNA (miRNA)-target complementarity has long been considered the
      predominant factor determining the silencing outcome of the miRNA-target
      interaction, although the efficacy of such interactions have rarely been
      appraised in plants. Here, we perform in planta silencing efficacy assays on
      seven Arabidopsis MYB genes, all of which contain conserved miR159-binding sites
      of analogous complementarity. These genes were found to be differentially
      silenced by miR159; MYB81, MYB97, MYB101, MYB104, and DUO1 were all poorly
      silenced, whereas MYB33 and MYB65 were strongly silenced. Curiously, this is
      consistent with previous genetic analysis defining MYB33 and MYB65 as the major
      functional targets of miR159. Neither the free energy of miR159-target
      complementarity, nor miRNA binding site accessibility, as determined by flanking
      region AU content, could fully explain the discrepancy of miR159 silencing
      efficacy. Instead, we found that MYB33 and MYB65 were both predicted to contain a
      distinctive RNA secondary structure abutting the miR159 binding site. The
      structure is composed of two stem-loops (SLs) that are predicted to form in
      MYB33/65 homologs of species as evolutionary distant as gymnosperms. Functional
      analysis found that the RNA structure in MYB33 correlated with strong silencing
      efficacy; introducing mutations to disrupt either SL attenuated miR159 efficacy,
      while introducing complementary mutations to restore the SLs, but not the
      sequence, restored strong miR159-mediated silencing. Therefore, it appears that
      this RNA secondary structure demarcates MYB33/65 as sensitive targets of miR159,
      which underpins the narrow functional specificity of Arabidopsis miR159.

PMID- 28515147
TI  - Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse
      Model of Prostate Carcinogenesis.
AB  - Prostate cancer does not appear to respond to immune checkpoint therapies where T
      cell infiltration may be a key limiting factor. Here, we report evidence that
      ablating the growth regulatory kinase Erk5 can increase T-cell infiltration in an
      established Pten-deficient mouse model of human prostate cancer. Mice that were
      doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a
      markedly increased median survival with reduced tumor size and proliferation
      compared with control Pten-mutant mice, the latter of which exhibited increased
      Erk5 mRNA expression. A comparative transcriptomic analysis revealed upregulation
      in prostate DKO mice of the chemokines Ccl5 and Cxcl10, two potent
      chemoattractants for T lymphocytes. Consistent with this effect, we observed a
      relative increase in a predominantly CD4+ T-cell infiltrate in the prostate
      epithelial and stroma of tumors from DKO mice. Collectively, our results offer a
      preclinical proof of concept for ERK5 as a target to enhance T-cell infiltrates
      in prostate cancer, with possible implications for leveraging immune therapy in
      this disease. Cancer Res; 77(12); 3158-68. (c)2017 AACR.

PMID- 28515148
TI  - NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor
      Suppressor PML in Breast Cancer.
AB  - The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in
      breast cancer remains controversial. Here we report a beneficial mechanism of E+P
      treatment in breast cancer cells driven by transcriptional upregulation of the
      NFkappaB modulator NEMO, which in turn promotes expression of the tumor
      suppressor protein promyelocytic leukemia (PML). E+P treatment of patient-derived
      epithelial cells derived from ductal carcinoma in situ (DCIS) increased secretion
      of the proinflammatory cytokine IL6. Mechanistic investigations indicated that
      IL6 upregulation occurred as a result of transcriptional upregulation of NEMO,
      the gene that harbored estrogen receptor (ER) binding sites within its promoter.
      Accordingly, E+P treatment of breast cancer cells increased ER binding to the
      NEMO promoter, thereby increasing NEMO expression, NFkappaB activation, and IL6
      secretion. In two mouse xenograft models of DCIS, we found that RNAi-mediated
      silencing of NEMO increased tumor invasion and progression. This seemingly
      paradoxical result was linked to NEMO-mediated regulation of NFkappaB and IL6
      secretion, increased phosphorylation of STAT3 on Ser727, and increased expression
      of PML, a STAT3 transcriptional target. In identifying NEMO as a pivotal
      transcriptional target of E+P signaling in breast cancer cells, our work offers a
      mechanistic explanation for the paradoxical antitumorigenic roles of E+P in
      breast cancer by showing how it upregulates the tumor suppressor protein PML.
      Cancer Res; 77(14); 3802-13. (c)2017 AACR.

PMID- 28515146
TI  - Transcriptome Profiling of Wheat Inflorescence Development from Spikelet
      Initiation to Floral Patterning Identified Stage-Specific Regulatory Genes.
AB  - Early reproductive development in cereals is crucial for final grain number per
      spike and hence the yield potential of the crop. To date, however, no systematic
      analyses of gene expression profiles during this important process have been
      conducted for common wheat (Triticum aestivum). Here, we studied the
      transcriptome profiles at four stages of early wheat reproductive development,
      from spikelet initiation to floral organ differentiation. K-means clustering and
      stage-specific transcript identification detected dynamically expressed homeologs
      of important transcription regulators in spikelet and floral meristems that may
      be involved in spikelet initiation, floret meristem specification, and floral
      organ patterning, as inferred from their homologs in model plants. Small RNA
      transcriptome sequencing discovered key microRNAs that were differentially
      expressed during wheat inflorescence development alongside their target genes,
      suggesting that miRNA-mediated regulatory mechanisms for floral development may
      be conserved in cereals and Arabidopsis. Our analysis was further substantiated
      by the functional characterization of the ARGONAUTE1d (AGO1d) gene, which was
      initially expressed in stamen primordia and later in the tapetum during anther
      maturation. In agreement with its stage-specific expression pattern, the loss of
      function of the predominantly expressed B homeolog of AGO1d in a tetraploid durum
      wheat mutant resulted in smaller anthers with more infertile pollens than the
      wild type and a reduced grain number per spike. Together, our work provides a
      first glimpse of the gene regulatory networks in wheat inflorescence development
      that may be pivotal for floral and grain development, highlighting potential
      targets for genetic manipulation to improve future wheat yields.

PMID- 28515149
TI  - Pyruvate Kinase Inhibits Proliferation during Postnatal Cerebellar Neurogenesis
      and Suppresses Medulloblastoma Formation.
AB  - Aerobic glycolysis supports proliferation through unresolved mechanisms. We have
      previously shown that aerobic glycolysis is required for the regulated
      proliferation of cerebellar granule neuron progenitors (CGNP) and for the growth
      of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via
      deletion of hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts
      medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M
      (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP
      metabolism, proliferation, and tumorigenesis. We observed a dichotomous pattern
      of PKM expression, in which postmitotic neurons throughout the brain expressed
      the constitutively active PKM1 isoform, while neural progenitors and
      medulloblastomas exclusively expressed the less active PKM2. Isoform-specific
      Pkm2 deletion in CGNPs blocked all Pkm expression. Pkm2-deleted CGNPs showed
      reduced lactate production and increased SHH-driven proliferation. 13C-flux
      analysis showed that Pkm2 deletion reduced the flow of glucose carbons into
      lactate and glutamate without markedly increasing glucose-to-ribose flux. Pkm2
      deletion accelerated tumor formation in medulloblastoma-prone ND2:SmoA1 mice,
      indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect.
      These findings show that distal and proximal disruptions of glycolysis have
      opposite effects on proliferation, and that efforts to block the oncogenic effect
      of aerobic glycolysis must target reactions upstream of PKM. Cancer Res; 77(12);
      3217-30. (c)2017 AACR.

PMID- 28515151
TI  - Assessing the satisfaction and burden within an academic animal care and use
      program.
AB  - Although animal research requires adherence to various regulations and standards,
      the manner in which compliance is maintained and the degree of additional
      constraints varies between institutions. Regulatory burden, particularly if
      institutionally imposed, has become a concern for institutions as increased
      regulatory expectations result in decreased resources available for research
      efforts. Faculty, research staff, and support staff engaged in animal research
      were surveyed to determine what institutional animal care and use committee
      (IACUC) processes were considered burdensome, the perceived value of some
      suggested modifications, and satisfaction with the IACUC administrative office
      and the animal resource unit. Although the results revealed overwhelming
      satisfaction with the IACUC administrative office and the animal resource unit,
      several IACUC processes were deemed burdensome, and therefore there would be
      value in modifying IACUC processes. When comparing the value of modifying IACUC
      processes, different groups within the animal care and use program (ACUP) tended
      to have different responses on many of the topics. This survey identified several
      perceived burdensome IACUC processes that would likely benefit individuals if
      modified. In today's environment of shrinking budgets for biomedical research,
      minimizing regulatory burden-particularly unnecessary, self-imposed burden-in the
      ACUP is particularly important to ensure that costs, time, and effort are
      appropriate to achieve animal welfare and quality of research endeavors.-Norton,
      J. N., Reynolds, R. P., Chan, C., Valdivia, R. H., Staats, H. F. Assessing the
      satisfaction and burden within an academic animal care and use program.

PMID- 28515150
TI  - Receptor for advanced glycation end products is targeted by FBXO10 for
      ubiquitination and degradation.
AB  - The receptor for advanced glycation end products (RAGE) is a highly expressed
      cell membrane receptor serving to anchor lung epithelia to matrix components, and
      it also amplifies inflammatory signaling during acute lung injury. However,
      mechanisms that regulate its protein concentrations in cells remain largely
      unknown. Here we show that RAGE exhibits an extended life span in lung epithelia
      (t1/2 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE
      ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic
      hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through
      activation of protein kinase Czeta (PKCzeta), which phosphorylates RAGE. PKCzeta
      overexpression enhances RAGE degradation, while PKCzeta knockdown stabilizes RAGE
      protein levels and prevents ODN2006-mediated degradation. We identify that RAGE
      is targeted by the ubiquitin E3 ligase subunit F-box protein O10 (FBXO10), which
      associates with RAGE to mediate its ubiquitination and degradation. FBXO10
      depletion in cells stabilizes RAGE and is required for ODN2006-mediated
      degradation. These data suggest that modulation of regulators involved in
      ubiquitin-mediated disposal of RAGE might serve as unique molecular inputs
      directing RAGE cellular concentrations and downstream responses, which are
      critical in an array of inflammatory disorders, including acute lung injury.
      Evankovich, J., Lear, T., Mckelvey, A., Dunn, S., Londino, J., Liu, Y., Chen, B.
      B., Mallampalli, R. K. Receptor for advanced glycation end products is targeted
      by FBXO10 for ubiquitination and degradation.

PMID- 28515152
TI  - Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal
      organization: a mechanism for diminished nuclear factor of activated T cells
      cytoplasmic 1 during osteoclastogenesis.
AB  - Kelch-like ECH-associated protein 1 (Keap1) binds to nuclear factor E2 p45
      related factor 2 (Nrf2), a transcription factor for antioxidant enzymes, to
      suppress Nrf2 activation. The role of oxidative stress in many diseases supports
      the possibility that processes that are associated with Nrf2 activation might
      offer therapeutic potential. Nrf2 deficiency induces osteoclastogenesis, which is
      responsible for bone loss, by activating receptor activator of NF-kappaB ligand
      (RANKL)-mediated signaling; however, the effects of Keap1 deficiency remain
      unclear. By using Keap1-deficient newborn mice, we observed that talus and
      calcaneus bone formation was partially retarded and that osteoclast number was
      reduced in vivo without severe gross abnormalities. In addition, Keap1-deficient
      macrophages were unable to differentiate into osteoclasts in vitrovia attenuation
      of RANKL-mediated signaling and expression of nuclear factor of activated T cells
      cytoplasmic 1 (NFATc1), a key transcription factor that is involved in
      osteoclastogenesis. Furthermore, Keap1 deficiency up-regulated the expression of
      Mafb, a negative regulator of NFATc1. RANKL-induced mitochondrial gene expression
      is required for down-regulation of IFN regulatory factor 8 (IRF-8), a negative
      transcriptional regulator of NFATc1. Our results indicate that Keap1 deficiency
      down-regulated peroxisome proliferator-activated receptor-gamma coactivator 1beta
      and mitochondrial gene expression and up-regulated Irf8 expression. These results
      suggest that the Keap1/Nrf2 axis plays a critical role in NFATc1 expression and
      osteoclastogenic progression.-Sakai, E., Morita, M., Ohuchi, M., Kido, M. A.,
      Fukuma, Y., Nishishita, K., Okamoto, K., Itoh, K., Yamamoto, M., Tsukuba, T.
      Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal
      organization: a mechanism for diminished nuclear factor of activated T cells
      cytoplasmic 1 during osteoclastogenesis.

PMID- 28515153
TI  - Differential regulation of renal Klotho and FGFR1 in normal and uremic rats.
AB  - In renal failure, hyperphosphatemia occurs despite a marked elevation in serum
      fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho
      receptor complex may cause a resistance to the phosphaturic action of FGF23. The
      purpose of the present study was to investigate the regulation of renal Klotho
      and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy.
      In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and
      increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic
      rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked
      elevation of FGF23 and an increased fractional excretion of phosphate (P) that
      was associated with a marked reduction of Klotho expression and an increase in
      FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia
      was still abundant, Klotho expression remained low, and the FGFR1 level was
      reduced. These results suggest that the expression of renal Klotho is modulated
      by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol
      (CTR) administration prevented a decrease in renal Klotho expression. In HEK293
      cells HP produced nuclear translocation of beta-catenin, together with a
      reduction in Klotho. Wnt/beta-catenin inhibition with Dkk-1 prevented the P
      induced down-regulation of Klotho. The addition of CTR to HP medium was able to
      recover Klotho expression. In summary, high FGF23 levels increase FGFR1, whereas
      phosphaturia decreases Klotho expression through the activation of Wnt/beta
      catenin pathway.-Munoz-Castaneda, J. R., Herencia, C., Pendon-Ruiz de Mier, M.
      V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martinez-Moreno, J.
      M., Salmeron, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almaden, Y.,
      Rodriguez, M. Differential regulation of renal Klotho and FGFR1 in normal and
      uremic rats.

PMID- 28515155
TI  - Building an Ideal Quality Metric for ESRD Health Care Delivery.

PMID- 28515154
TI  - Progerin sequestration of PCNA promotes replication fork collapse and
      mislocalization of XPA in laminopathy-related progeroid syndromes.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is
      caused by a point mutation in the LMNA gene, resulting in production of a
      truncated farnesylated-prelamin A protein (progerin). We previously reported that
      XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites,
      blocking DSB repair, which led to DSB accumulation, DNA damage responses, and
      early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs
      occurred at stalled or collapsed replication forks, concurrent with a significant
      loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA
      sequestration likely exposed ds-ssDNA junctions at replication forks for XPA
      binding. Depletion of XPA or progerin each significantly restored PCNA at
      replication forks. Our results suggest that although PCNA is much more
      competitive than XPA in binding replication forks, PCNA sequestration by progerin
      may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that
      progerin-induced apoptosis could be rescued by XPA, suggesting that XPA
      replication fork binding may prevent apoptosis in HGPS cells. Our results propose
      a mechanism for progerin-induced genome instability and accelerated replicative
      senescence in HGPS.-Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman,
      M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Progerin
      sequestration of PCNA promotes replication fork collapse and mislocalization of
      XPA in laminopathy-related progeroid syndromes.

PMID- 28515157
TI  - Carboxyamidotriazole Synergizes with Sorafenib to Combat Non-Small Cell Lung
      Cancer through Inhibition of NANOG and Aggravation of Apoptosis.
AB  - Lung cancer is currently the leading cause of cancer-related deaths worldwide. In
      this study, we investigated the combination of carboxyamidotriazole (CAI) and
      sorafenib in non-small cell lung cancer (NSCLC) in vitro and in vivo to test
      whether CAI enhances the antitumor effects of sorafenib and reduces its side
      effects. The combination index (CI) showed that coadministration of CAI and
      sorafenib synergistically inhibited the proliferation of NSCLC cells (Lewis lung
      carcinoma, A549, and NCI-H1975 cells). Cell death as a result of the combination
      treatment was attributed to apoptosis, which was accompanied by activation of
      caspase-3 and poly(ADP-ribose) polymerase. In addition, combination therapy
      induced the accumulation of mitochondrial-associated reactive oxygen species, as
      well as depolarization of mitochondrial and reduced NANOG (homeobox protein
      NANOG) mRNA and protein expression. Basic fibroblast growth factor, a stimulator
      of NANOG, was applied to identify the possible mechanism. The addition of basic
      fibroblast growth factor followed by combined treatment may stimulate NANOG
      expression and synchronously rescue the accumulation of reactive oxygen species.
      C57BL/6J mice bearing Lewis lung carcinoma were randomized to receive vehicle
      (polyethylene glycol 400), CAI (30 mg/kg), low-dose sorafenib (SFB-L; 10 mg/kg),
      high-dose sorafenib (SFB-H; 30 mg/kg), or a CAI and SFB-L combination. Tumor
      growth was significantly suppressed in the combination group, and the efficacy of
      combination treatment was equivalent to that of the SFB-H monotherapy group.
      Furthermore, the combination group had reduced side effects compared with the SFB
      H group, as indicated by weight preservation in mice. Our study illustrates that
      CAI enhances the antitumor activity of sorafenib in NSCLC and provides a novel
      strategy for NSCLC treatment.

PMID- 28515156
TI  - Anti-Glomerular Basement Membrane Disease.
AB  - Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel
      vasculitis that affects the capillary beds of the kidneys and lungs. It is an
      archetypic autoimmune disease, caused by the development of directly pathogenic
      autoantibodies targeting a well characterized autoantigen expressed in the
      basement membranes of these organs, although the inciting events that induce the
      autoimmune response are not fully understood. The recent confirmation of spatial
      and temporal clustering of cases suggests that environmental factors, including
      infection, may trigger disease in genetically susceptible individuals. The
      majority of patients develop widespread glomerular crescent formation, presenting
      with features of rapidly progressive GN, and 40%-60% will have concurrent
      alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody,
      typically with the use of plasma exchange, along with steroids and cytotoxic
      therapy to prevent ongoing autoantibody production and tissue inflammation.
      Retrospective cohort studies suggest that when this combination of treatment is
      started early, the majority of patients will have good renal outcome, although
      presentation with oligoanuria, a high proportion of glomerular crescents, or
      kidney failure requiring dialysis augur badly for renal prognosis. Relapse and
      recurrent disease after kidney transplantation are both uncommon, although de
      novo anti-GBM disease after transplantation for Alport syndrome is a recognized
      phenomenon. Copresentation with other kidney diseases such as ANCA-associated
      vasculitis and membranous nephropathy seems to occur at a higher frequency than
      would be expected by chance alone, and in addition atypical presentations of anti
      GBM disease are increasingly reported. These observations highlight the need for
      future work to further delineate the immunopathogenic mechanisms of anti-GBM
      disease, and how to better refine and improve treatments, particularly for
      patients presenting with adverse prognostic factors.

PMID- 28515158
TI  - Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2
      Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression.
AB  - Oxidative stress contributes to inflammatory skin diseases, including psoriasis.
      Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood
      mechanism of action. In other cell types MMF increases the expression of nuclear
      factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates
      cellular antioxidant responses, to reduce oxidative stress like that observed in
      inflammatory disorders such as multiple sclerosis. We tested the hypothesis that
      MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to
      counteract environmental stresses. We used Western analysis, immunofluorescence,
      and real-time quantitative reverse-transcription polymerase chain reaction to
      examine the effect of MMF on the expression of Nrf2 and its targets. We also
      measured intracellular reactive oxygen species (ROS) levels following MMF
      treatment. Our data show that MMF increased total and nuclear Nrf2 levels in
      primary mouse keratinocytes and enhanced mRNA expression of several Nrf2
      downstream effectors, including heme oxygenase-1 and peroxiredoxin-6. Moreover,
      MMF treatment attenuated the generation of ROS following hydrogen peroxide
      treatment. On the other hand, the expression and membranous localization of
      aquaporin-3 (AQP3), a glycerol channel implicated in keratinocyte
      differentiation, was stimulated by MMF, which also enhanced keratinocyte glycerol
      uptake. The Nrf2 activator sulforaphane also increased AQP3 levels, suggesting
      that AQP3 expression may be regulated by Nrf2. We show for the first time that
      MMF stimulates Nrf2 and AQP3 expression and function/activity in keratinocytes.
      This effect may account, in part, for the previously observed ability of MMF to
      inhibit proliferation and inflammatory mediator production and promote
      differentiation in keratinocytes and to treat psoriasis.

PMID- 28515159
TI  - Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of
      Chronic Cerebral Hypoperfusion.
AB  - Background: Whether intermittent fasting (IF) pretreatment can prevent vascular
      cognitive dysfunction remains unknown to our knowledge.Objective: We investigated
      the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction
      in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male
      Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for
      12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed
      deprivation (FD). Memory of the animals was assessed by using the Morris water
      maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery.
      After behavioral testing, malondialdehyde and glutathione concentrations,
      superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes,
      inflammatory protein concentrations, and microglia density were determined in the
      hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL)
      rats had significantly longer escape latencies on day 4 of the training phase and
      spent a lower percentage of time in the target quadrant (25% compared with 38%
      and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65%
      and 67%) in the NOR test than 2-vessel operation and alternate-day feed
      deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively
      (P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits.
      2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66
      nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41
      and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and
      138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher
      expression of inflammatory proteins, and higher microglia density in the
      hippocampus than 2VO-FD and Sham-AL rats, respectively (P < 0.05). This suggests
      that IF has antioxidative and anti-inflammatory effects.Conclusions: IF
      pretreatment provided sustained neuroprotection in a rat model of vascular
      dementia. These effects were associated with reduced oxidative stress and
      neuroinflammation.

PMID- 28515160
TI  - Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated
      Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or
      Obese Adults with Elevated Triglycerides.
AB  - Background: Hypertriglyceridemia is a common condition in the United States and
      is often associated with other metabolic disturbances, including insulin
      resistance, metabolic syndrome, and a predominance of small dense LDL
      particles.Objective: The objective of this trial was to evaluate the effects of a
      combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted
      for refined starches and added sugars on insulin sensitivity (primary outcome)
      and other cardiometabolic health markers in overweight or obese adults with
      elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG
      concentrations were given test foods prepared by using Epro powder (~8% of
      energy) and vegetable oil (~8% of energy; Epro and UFA condition) or test foods
      prepared by using refined starch and sugar (~16% of energy; carbohydrate
      condition) in a randomized, double-blind, controlled-feeding, crossover trial (3
      wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI),
      fasting lipids, and other cardiometabolic health markers were assessed at
      baseline and the end of each diet condition. Responses were compared by using
      repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women;
      mean +/- SEM: age, 46.3 +/- 2.4 y; body mass index (in kg/m2), 31.8 +/- 1.0] with
      a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL
      (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% +/- 8.7%
      from baseline during the Epro and UFA condition and decreased 5.7% +/- 6.2% from
      baseline during the carbohydrate condition (P < 0.001). The disposition index
      increased 23.8% +/- 20.8% during the Epro and UFA condition compared with a
      decrease of 16.3% +/- 18.8% during carbohydrate (P = 0.042) and LDL peak particle
      size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a
      decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL
      cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (
      34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (
      13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet
      condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with
      a combination of Epro and UFA increased the MISI value and altered several
      markers of cardiometabolic health in overweight or obese adults with elevated TG
      concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.

PMID- 28515161
TI  - Suboptimal Maternal Iodine Intake Is Associated with Impaired Child
      Neurodevelopment at 3 Years of Age in the Norwegian Mother and Child Cohort
      Study.
AB  - Background: Severe iodine deficiency in pregnancy has major effects on child
      neurodevelopment, but less is known about the potential consequences of mild-to
      moderate deficiency and iodine supplement use.Objective: We explored the
      associations between maternal iodine intake and child neurodevelopment at 3 y of
      age and the potential impact of maternal intake of iodine from supplements on the
      same outcomes.Methods: This population-based prospective observational study
      included 48,297 mother-child pairs recruited during pregnancy from 2002 to 2008.
      Maternal iodine intake was calculated based on a validated food-frequency
      questionnaire answered during midpregnancy that covered mean intake since the
      beginning of pregnancy. Associations between iodine intake and maternal-reported
      child language and motor development and behavior problems were explored by
      multivariable regression analyses.Results: In 33,047 mother-child pairs,
      excluding iodine supplement users, maternal iodine intake was associated with
      child language delay (P = 0.024), externalizing and internalizing behavior
      problems (both P < 0.001), and fine motor skills (P = 0.002) but not gross motor
      skills or the risk of not walking unaided at 17 mo of age. In 74% of the
      participants who had an iodine intake <160 MUg/d (Estimated Average Requirement),
      suboptimal iodine intake was estimated to account for ~5% (95% CI: -5%, 14%) of
      the cases of language delay, 16% (95% CI: 0%, 21%) of the cases of externalizing
      behavior problems >1.5 SD, and 16% (95% CI: 10%, 21%) of the cases of
      internalizing behavior problems >1.5 SD. In 48,297 mother-child pairs, including
      iodine supplement users, we found no protective effects of supplemental iodine
      during pregnancy on neurodevelopment.Conclusions: Maternal iodine intake below
      the Estimated Average Requirement during pregnancy was associated with symptoms
      of child language delay, behavior problems, and reduced fine motor skills at 3 y
      of age. The results showed no evidence of a protective effect of iodine
      supplementation during pregnancy.

PMID- 28515162
TI  - Dietary Protein and the Health-Nutrition-Agriculture Connection in India.
AB  - The connection between the production, availability, and consumption of high
      quality food is becoming very important in developing countries. The requirement
      of protein is linked to its quality, or its digestibility and ability to meet
      human indispensable amino acid requirements. This requirement is particularly
      relevant in India, where commonly consumed cereal-based diets and cereal-based
      food subsidy programs offer low-quality protein and therefore pose a risk of
      quality protein deficiency. The production of and access to sustainable sources
      of high-quality protein will be important parts of mitigating risks to human
      health. Although milk production has risen in India, its consumption by the poor
      remains low. On the other hand, leguminous grain production, which has greater
      climate resilience and soil improvement properties, has fallen, yet this can help
      resource-poor farmers increase their intake of quality food. Nonetheless,
      concerns about the nutritional quality of plant protein exist and may be more
      relevant in settings where environmental enteric dysfunction already affects
      nutrient absorption. With the use of nationally representative household protein
      consumption data in India, the percentage of the population at risk of quality
      protein deficiency was found to vary between 4% and 26% among different age
      groups and between the urban or rural sector. Mitigating these risks requires a
      greater intake of high-quality proteins, such as pulses and milk, and that food
      subsidy policies move beyond cereals and become more quality conscious.

PMID- 28515163
TI  - Assessment of Nitric Oxide Production in Mitochondrial Encephalomyopathy, Lactic
      Acidosis, and Stroke-Like Episodes Syndrome with the Use of a Stable Isotope
      Tracer Infusion Technique.
AB  - Mitochondrial disorders result from dysfunctional mitochondria that are unable to
      generate sufficient energy to meet the needs of various organs. Mitochondrial
      encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is
      one of the most frequent maternally inherited mitochondrial disorders. There is
      growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and
      results in impaired blood perfusion that contributes significantly to several
      complications in this disease. NO is synthesized from arginine by NO synthase,
      which catalyzes the conversion of arginine to NO and citrulline. Citrulline can
      be recycled into arginine, and therefore, both arginine and citrulline support NO
      synthesis. The use of 15N2-arginine and 13C-,2H4-citrulline stable isotope
      infusion allows measuring arginine flux; citrulline flux; citrulline-to-arginine
      flux, which represents the de novo arginine synthesis rate; and arginine-to
      citrulline flux, which represents the NO production rate. The objective of this
      review is to highlight the utility of this method in providing additional
      evidence for NO deficiency in MELAS syndrome, adding more insight into the
      potential mechanisms of NO deficiency in this syndrome, and allowing for the
      assessment of the effects of supplementation with the NO donors, arginine and
      citrulline, on improving NO production in MELAS syndrome.

PMID- 28515168
TI  - The origin of the 'channel arrest' hypothesis.

PMID- 28515165
TI  - Zinc Supplementation, via GPR39, Upregulates PKCzeta to Protect Intestinal
      Barrier Integrity in Caco-2 Cells Challenged by Salmonella enterica Serovar
      Typhimurium.
AB  - Background: Zinc has been shown to improve intestinal barrier function against
      Salmonella enterica serovar Typhimurium (S. typhimurium) infection, but the
      mechanisms involved in this process remain undefined.Objective: We aimed to
      explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Czeta
      (PKCzeta) in the regulation by zinc of intestinal barrier function.Methods: A
      Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 MUM Zn and then
      incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small
      interfering RNA for GPR39 or PKCzeta were pretreated with 100 MUM Zn and
      incubated with S. typhimurium for 3 h. Finally, transepithelial electrical
      resistance (TEER), permeability, tight junction (TJ) proteins, and signaling
      molecules GPR39 and PKCzeta were measured.Results: Compared with controls, S.
      typhimurium decreased TEER by 62.3-96.2% at 4-6 h (P < 0.001), increased (P <
      0.001) permeability at 6 h, and downregulated (P < 0.05) TJ protein zonula
      occludens (ZO)-1 and occludin by 104-123%, as well as Toll-like receptor 2 and
      PKCzeta by 35.1% and 75.2%, respectively. Compared with S. typhimurium-challenged
      cells, 50 and 100 MUM Zn improved TEER by 26.3-60.9% at 4-6 h (P < 0.001) and
      decreased (P < 0.001) permeability and bacterial invasion at 6 h. A total of 100
      MUM Zn increased ZO-1, occludin, GPR39, and PKCzeta 0.72- to 1.34-fold (P <
      0.05); however, 50 MUM Zn did not affect ZO-1 or occludin (P > 0.1). Silencing
      GPR39 decreased (P < 0.05) zinc-activated PKCzeta and blocked (P < 0.05) the
      promotion of zinc on epithelial integrity. Furthermore, silencing PKCzeta
      counteracted the protective effect of zinc on epithelial integrity but did not
      inhibit GPR39 (P = 0.138).Conclusion: We demonstrated that zinc upregulates
      PKCzeta by activating GPR39 to enhance the abundance of ZO-1, thereby improving
      epithelial integrity in S. typhimurium-infected Caco-2 cells.

PMID- 28515164
TI  - mRNA Levels of Placental Iron and Zinc Transporter Genes Are Upregulated in
      Gambian Women with Low Iron and Zinc Status.
AB  - Background: The role of the placenta in regulating micronutrient transport in
      response to maternal status is poorly understood.Objective: We investigated the
      effect of prenatal nutritional supplementation on the regulation of placental
      iron and zinc transport.Methods: In a randomized trial in rural Gambia [ENID
      (Early Nutrition and Immune Development)], pregnant women were allocated to 1 of
      4 nutritional intervention arms: 1) iron and folic acid (FeFol) tablets (FeFol
      group); 2) multiple micronutrient (MMN) tablets (MMN group); 3) protein energy
      (PE) as a lipid-based nutrient supplement (LNS; PE group); and 4) PE and MMN
      (PE+MMN group) as LNS. All arms included iron (60 mg/d) and folic acid (400
      MUg/d). The MMN and PE+MMN arms included 30 mg supplemental Zn/d. In a subgroup
      of ~300 mother-infant pairs, we measured maternal iron status, mRNA levels of
      genes encoding for placental iron and zinc transport proteins, and cord blood
      iron levels.Results: Maternal plasma iron concentration in late pregnancy was 45%
      and 78% lower in the PE and PE+MMN groups compared to the FeFol and MMN groups,
      respectively (P < 0.001). The mRNA levels of the placental iron uptake protein
      transferrin receptor 1 were 30-49% higher in the PE and PE+MMN arms than in the
      FeFol arm (P < 0.031), and also higher in the PE+MMN arm (29%; P = 0.042) than in
      the MMN arm. Ferritin in infant cord blood was 18-22% lower in the LNS groups (P
      < 0.024). Zinc supplementation in the MMN arm was associated with higher maternal
      plasma zinc concentrations (10% increase; P < 0.001) than in other intervention
      arms. mRNA levels for intracellular zinc-uptake proteins, in this case zrt, irt
      like protein (ZIP) 4 and ZIP8, were 96-205% lower in the PE+MMN arm than in the
      intervention arms without added zinc (P < 0.025). Furthermore, mRNA expression of
      ZIP1 was 85% lower in the PE+MMN group than in the PE group (P =
      0.003).Conclusion: In conditions of low maternal iron and in the absence of
      supplemental zinc, the placenta upregulates the gene expression of iron and zinc
      uptake proteins, presumably in order to meet fetal demands in the face of low
      maternal supply. The ENID trial was registered at www.controlled-trials.com as
      ISRCTN49285450.

PMID- 28515169
TI  - Osmoregulation, bioenergetics and oxidative stress in coastal marine
      invertebrates: raising the questions for future research.
AB  - Osmoregulation is by no means an energetically cheap process, and its costs have
      been extensively quantified in terms of respiration and aerobic metabolism.
      Common products of mitochondrial activity are reactive oxygen and nitrogen
      species, which may cause oxidative stress by degrading key cell components, while
      playing essential roles in cell homeostasis. Given the delicate equilibrium
      between pro- and antioxidants in fueling acclimation responses, the need for a
      thorough understanding of the relationship between salinity-induced oxidative
      stress and osmoregulation arises as an important issue, especially in the context
      of global changes and anthropogenic impacts on coastal habitats. This is
      especially urgent for intertidal/estuarine organisms, which may be subject to
      drastic salinity and habitat changes, leading to redox imbalance. How do
      osmoregulation strategies determine energy expenditure, and how do these
      processes affect organisms in terms of oxidative stress? What mechanisms are used
      to cope with salinity-induced oxidative stress? This Commentary aims to highlight
      the main gaps in our knowledge, covering all levels of organization. From an
      energy-redox perspective, we discuss the link between environmental salinity
      changes and physiological responses at different levels of biological
      organization. Future studies should seek to provide a detailed understanding of
      the relationship between osmoregulatory strategies and redox metabolism, thereby
      informing conservation physiologists and allowing them to tackle the new
      challenges imposed by global climate change.

PMID- 28515170
TI  - Respiratory function and mechanics in pinnipeds and cetaceans.
AB  - In this Review, we focus on the functional properties of the respiratory system
      of pinnipeds and cetaceans, and briefly summarize the underlying anatomy; in
      doing so, we provide an overview of what is currently known about their
      respiratory physiology and mechanics. While exposure to high pressure is a common
      challenge among breath-hold divers, there is a large variation in respiratory
      anatomy, function and capacity between species - how are these traits adapted to
      allow the animals to withstand the physiological challenges faced during dives?
      The ultra-deep diving feats of some marine mammals defy our current understanding
      of respiratory physiology and lung mechanics. These animals cope daily with lung
      compression, alveolar collapse, transient hyperoxia and extreme hypoxia. By
      improving our understanding of respiratory physiology under these conditions, we
      will be better able to define the physiological constraints imposed on these
      animals, and how these limitations may affect the survival of marine mammals in a
      changing environment. Many of the respiratory traits to survive exposure to an
      extreme environment may inspire novel treatments for a variety of respiratory
      problems in humans.

PMID- 28515171
TI  - Mutualistic damselfish induce higher photosynthetic rates in their host coral.
AB  - Coral reefs are amongst the most diverse ecosystems on Earth where complex inter
      specific interactions are ubiquitous. An example of such interactions is the
      mutualistic relationship between damselfishes and branching corals in the
      Northern Red Sea, where the fish use corals as shelter and provide them with
      nutrients, enhance the flow between their branches, and protect them from
      predators. By enhancing the flow between the coral branches, the fish ventilate
      the coral's inner zone, mitigating hypoxic conditions that otherwise develop
      within that zone during the night. Here, we tested, for the first time, the
      effects of the damselfish Dascyllus marginatus on photosynthesis and respiration
      in its host coral Stylophora pistillata Laboratory experiments using an
      intermittent-flow respirometer showed that the presence of fish between the coral
      branches under light conditions augmented the coral's photosynthetic rate. No
      effect on the coral's respiration was found under dark conditions. When a fish
      was allowed to enter the inner zone of a dead coral skeleton, its respiration was
      higher than when it was in a live coral. Field observations indicated that
      damselfish were present between coral branches 18-34% of the time during daylight
      hours and at all times during the night. Considering the changes induced by the
      fish together with the proportion of time they were found between coral branches
      in the field, the effect of the fish amounted to an augmentation of 3-6% of the
      coral's daily photosynthesis. Our findings reveal a previously unknown positive
      contribution of coral-dwelling fish to their host's photosynthesis.

PMID- 28515173
TI  - Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells.
AB  - Ferroptosis is an iron-dependent form of regulated nonapoptotic cell death, which
      contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1
      (HO-1) is a cytoprotective enzyme induced in response to cellular stress, and is
      protective against AKI because of its antiapoptotic and anti-inflammatory
      properties. However, the role of HO-1 in regulating ferroptosis is unclear. The
      purpose of this study was to elucidate the role of HO-1 in regulating ferroptotic
      cell death in renal proximal tubule cells (PTCs). Immortalized PTCs obtained from
      HO-1+/+ and HO-1-/- mice were treated with erastin or RSL3, ferroptosis inducers,
      in the presence or absence of antioxidants, an iron source, or an iron chelator.
      Cells were assessed for changes in morphology and metabolic activity as an
      indicator of cell viability. Treatment of HO-1+/+ PTCs with erastin resulted in a
      time- and dose-dependent increase in HO-1 gene expression and protein levels
      compared with vehicle-treated controls. HO-1-/- cells showed increased dose
      dependent erastin- or RSL3-induced cell death in comparison to HO-1+/+ PTCs. Iron
      supplementation with ferric ammonium citrate in erastin-treated cells decreased
      cell viability further in HO-1-/- PTCs compared with HO-1+/+ cells. Cotreatment
      with ferrostatin-1 (ferroptosis inhibitor), deferoxamine (iron chelator), or N
      acetyl-l-cysteine (glutathione replenisher) significantly increased cell
      viability and attenuated erastin-induced ferroptosis in both HO-1+/+ and HO-1-/-
      PTCs. These results demonstrate an important antiferroptotic role of HO-1 in
      renal epithelial cells.

PMID- 28515174
TI  - Functional assessment of sodium chloride cotransporter NCC mutants in polarized
      mammalian epithelial cells.
AB  - The thiazide-sensitive sodium chloride cotransporter NCC is important for
      maintaining serum sodium (Na+) and, indirectly, serum potassium (K+) levels.
      Functional studies on NCC have used cell lines with native NCC expression,
      transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here,
      we developed the use of polarized Madin-Darby canine kidney type I (MDCKI)
      mammalian epithelial cell lines with tetracycline-inducible human NCC expression
      to study NCC activity and membrane abundance in the same system. In radiotracer
      assays, induced cells grown on filters had robust thiazide-sensitive and chloride
      dependent sodium-22 (22Na) uptake from the apical side. To minimize cost and
      maximize throughput, assays were modified to use cells grown on plastic. On
      plastic, cells had similar thiazide-sensitive 22Na uptakes that increased
      following preincubation of cells in chloride-free solutions. NCC was detected in
      the plasma membrane, and both membrane abundance and phosphorylation of NCC were
      increased by incubation in chloride-free solutions. Furthermore, in cells exposed
      for 15 min to low or high extracellular K+, the levels of phosphorylated NCC
      increased and decreased, respectively. To demonstrate that the system allows
      rapid and systematic assessment of mutated NCC, three phosphorylation sites in
      NCC were mutated, and NCC activity was examined. 22Na fluxes in phosphorylation
      deficient mutants were reduced to baseline levels, whereas phosphorylation
      mimicking mutants were constitutively active, even without chloride-free
      stimulation. In conclusion, this system allows the activity, cellular
      localization, and abundance of wild-type or mutant NCC to be examined in the same
      polarized mammalian expression system in a rapid, easy, and low-cost fashion.

PMID- 28515172
TI  - Cross-sex transplantation alters gene expression and enhances inflammatory
      response in the transplanted kidneys.
AB  - Kidney transplantation (KTX) is a life-saving procedure for patients with end
      stage renal disease. Expression levels of many genes in the kidney vary between
      males and females, which may play an essential role in the sex differences in
      graft function. However, whether these differences are affected after cross-sex
      KTX is unknown. In the present study, we assessed postoperative changes in
      genotype, function, and inflammatory responses of the grafts in same-sex- and
      cross-sex-KTX. Single kidney transplants were performed between same and
      different sex C57BL/6 mice paired into four combination groups: female
      donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male
      recipient (F/M); and male donor/female recipient (M/F). The remnant native kidney
      was removed 4 days posttransplant. Expression levels of genes related to the
      contractility of the afferent arteriole and tubular sodium reabsorption were
      assessed. Same-sex-KTX did not significantly alter the magnitude or sex
      difference pattern of gene expression in male or female grafts. Cross-sex-KTX
      showed an attenuated sex difference in gene expressions. The measurements of
      endothelin 1, endothelin ETA receptor, Na+-K--2Cl cotransporter 2 (NKCC2), and
      epithelial Na+ channels (ENaC) subunits exhibited decreases in M/F compared with
      M/M and increases in F/M compared with F/F. There were no significant differences
      in hemodynamics or sodium excretion in response to acute volume expansion for any
      sex combinations. Cross-sex-KTX stimulated more robust inflammatory responses
      than same-sex-KTX. IL-6 and KC mRNA levels elevated 5- to 20-fold in cross-sex
      KTX compared with same-sex-KTX. In conclusion, cross-sex-KTX alters gene
      expression levels and induces inflammatory responses, which might play an
      important role in long-term graft function.

PMID- 28515175
TI  - Role for reactive oxygen species in flow-stimulated inner medullary collecting
      duct endothelin-1 production.
AB  - Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated
      by volume expansion, in part through augmented luminal flow, whereupon it can
      elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and
      reactive oxygen species (ROS), both of which can affect collecting duct salt
      transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1.
      Mouse IMCD3 cells were exposed to flow, and ET-1/GAPDH mRNA was assessed. A shear
      stress of 10 dyn/cm2 for 1 h increased ET-1 mRNA by fourfold compared with no
      flow (ET-1 flow response). Global NO synthase (NOS) inhibition [NG-nitro-l
      arginine methyl ester (l-NAME)] reduced the ET-1 flow response; however,
      pharmacological inhibition of NOS1 or NOS2, inhibition of NOS3 siRNA, inhibition
      of arginase inhibition, removal of media l-Arg, or inhibition of NO-dependent
      signaling pathways (PKG, guanylyl cyclase, or NF-kappaB) did not affect the ET-1
      flow response. Tempol reduced the ET-1 flow response; no further inhibition
      occurred with l-NAME. Superoxide dismutase, but not catalase, reduced the ET-1
      flow response. Inhibition of NAPDH oxidase (NOX) (apocynin), pharmacological
      inhibition of NOX1/4, or NOX4 siRNA reduced the ET-1 flow response. Finally, flow
      increased IMCD3 ROS production and this was inhibited by apocynin, NOX1/4
      inhibition, and, to a small extent, by l-NAME. Taken together, these data suggest
      that NOX4-derived ROS in general, and possibly superoxide in particular, are
      involved in flow-stimulated IMCD ET-1 production. To our knowledge, this is the
      first report of flow-stimulated ROS production by the CD, as well as the first
      report of such flow-stimulated CD ROS exerting a biological effect.

PMID- 28515177
TI  - Do beta3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by
      inhibiting acetylcholine release?

PMID- 28515176
TI  - Acute exercise does not impair renal function in nondialysis chronic kidney
      disease patients regardless of disease stage.
AB  - Exercise has been overlooked as a potential therapy in chronic kidney disease
      (CKD), mainly because of a lack of understanding on its safety aspects. Notably,
      there are no data on renal function after exercise in CKD considering its stages.
      We investigated the acute effects of a 30-min moderate-intensity aerobic exercise
      bout on glomerular filtration rate (GFR) and albuminuria in 22 nondialysis CKD
      patients divided into: CKD stages 1 and 2 (CKD1-2) and CKD stages 3 and 4 (CKD3
      4). Eleven body mass index-, age-, and sex-matched healthy individuals served as
      control (CON). Blood and urine samples were collected before, immediately after,
      and up to 90 min postexercise for creatinine and albumin assessments. GFR was
      determined by creatinine clearance (GFRCr-Cl). All CKD patients had significantly
      lower peak oxygen uptake than CON. CKD1-2 and CKD3-4 had increasingly higher
      serum creatinine than CON (9.6 +/- 2.6, 25.6 +/- 1.01, and 7.5 +/- 1.4 mg/l,
      respectively); however, no within-group changes in serum or urinary creatinine
      were observed across time. GFRCr-Cl was decreased in CKD1-2 and CKD3-4 compared
      with CON (91 +/- 17 ml.min-1.1.73 m-2; 34 +/- 15 ml.min-1.1.73 m-2; 122 +/- 20
      ml.min-1.1.73 m-2, respectively). Most importantly, exercise did not affect GFRCr
      Cl in none of the groups across time. Albuminuria was significantly higher in
      CKD3-4 (297 +/- 284 ug/min) than in CON (5.4 +/- 1.4 ug/min), but no within-group
      changes were observed after exercise. In conclusion, a single 30-min moderate
      intensity aerobic exercise bout does not impair renal function in nondialysis CKD
      patients, regardless of disease stage, supporting the notion that exercise
      training can be safe in this disease.

PMID- 28515178
TI  - A model-specific role of microRNA-223 as a mediator of kidney injury during
      experimental sepsis.
AB  - Sepsis outcomes are heavily dependent on the development of septic organ injury,
      but no interventions exist to interrupt or reverse this process. microRNA-223
      (miR-223) is known to be involved in both inflammatory gene regulation and host
      pathogen interactions key to the pathogenesis of sepsis. The goal of this study
      was to determine the role of miR-223 as a mediator of septic kidney injury. Using
      miR-223 knockout mice and multiple models of experimental sepsis, we found that
      miR-223 differentially influences acute kidney injury (AKI) based on the model
      used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile
      models of sepsis (LPS injection) and attenuated AKI in a live-infection model of
      sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is
      induced in kidney homogenate after cecal ligation and puncture, but not after LPS
      or fecal slurry injection. We investigated additional potential mechanistic
      explanations including differences in peritoneal bacterial clearance and host
      stool virulence. Our findings highlight the complex role of miR-223 in the
      pathogenesis of septic kidney injury, as well as the importance of differences in
      experimental sepsis models and their consequent translational applicability.

PMID- 28515180
TI  - Distribution and extent of electronic medical record utilisation in eye units
      across the United Kingdom: a cross-sectional study of the current landscape.
AB  - OBJECTIVES: Ophthalmology units across the UK vary widely in their adoption of
      electronic medical records (EMR). There is a lack of evidence to show the extent
      and progress of EMR adoption. The aim of this study was to capture a snapshot of
      the current landscape of EMR use, as a baseline for comparison in future studies.
      SETTING: An electronic survey questionnaire was sent to all NHS ophthalmology
      Units in the UK. PARTICIPANTS: A total of 104 National Health Service (NHS)
      ophthalmology units participated in the survey, which was carried out over 6
      months from December 2013 to June 2014. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Respondents were asked about technology usage pertaining to specific processes in
      the clinic workflow. This allowed us to determine the extent of EMR usage and
      details about current use or planned implementation by each unit. RESULTS: 77.6%
      (n=104) of NHS ophthalmology units responded. 45.3% (n=48) of units were
      currently using an EMR and a further 26.4% (n=28) of units plan to implement EMR
      within 2 years. 70.8% of units with a current EMR system use Medisoft. EMR is
      used by all clinicians in 37.5% and by all subspecialties offered at the unit in
      27.0%. In 56.3%, new clinical notes are entered into EMR only by clinicians. All
      imaging devices are networked to EMR in 28.3%. In 46.7%, EMR is accessible by
      other specialties within the same hospital. 71.1% would recommend EMR to a
      colleague. CONCLUSIONS: EMR has the potential to address current limitations of
      patient information transfer and sharing in ophthalmology. It is pleasing to see
      a significant proportion of units already engaging with EMR or having plans to do
      so in the near future. However, differing EMR systems and lack of remote access
      mean further optimisation of these record systems are needed to allow data
      transfer between units.

PMID- 28515181
TI  - Measuring ability to assess claims about treatment effects: the development of
      the 'Claim Evaluation Tools'.
AB  - OBJECTIVES: To describe the development of the Claim Evaluation Tools, a set of
      flexible items to measure people's ability to assess claims about treatment
      effects. SETTING: Methodologists and members of the community (including
      children) in Uganda, Rwanda, Kenya, Norway, the UK and Australia. PARTICIPANTS:
      In the iterative development of the items, we used purposeful sampling of people
      with training in research methodology, such as teachers of evidence-based
      medicine, as well as patients and members of the public from low-income and high
      income countries. Development consisted of 4 processes: (1) determining the scope
      of the Claim Evaluation Tools and development of items; (2) expert item review
      and feedback (n=63); (3) cognitive interviews with children and adult end-users
      (n=109); and (4) piloting and administrative tests (n=956). RESULTS: The Claim
      Evaluation Tools database currently includes a battery of multiple-choice items.
      Each item begins with a scenario which is intended to be relevant across
      contexts, and which can be used for children (from age 10  and above), adult
      members of the public and health professionals. People with expertise in research
      methods judged the items to have face validity, and end-users judged them
      relevant and acceptable in their settings. In response to feedback from
      methodologists and end-users, we simplified some text, explained terms where
      needed, and redesigned formats and instructions. CONCLUSIONS: The Claim
      Evaluation Tools database is a flexible resource from which researchers, teachers
      and others can design measurement instruments to meet their own requirements.
      These evaluation tools are being managed and made freely available for non
      commercial use (on request) through Testing Treatments interactive
      (testingtreatments.org). TRIAL REGISTRATION NUMBERS: PACTR201606001679337 and
      PACTR201606001676150; Pre-results.

PMID- 28515179
TI  - Arginase-2 mediates renal ischemia-reperfusion injury.
AB  - Novel therapeutic interventions for preventing or attenuating kidney injury
      following ischemia-reperfusion injury (IRI) remain a focus of significant
      interest. Currently, there are no definitive therapeutic or preventive approaches
      available for ischemic acute kidney injury (AKI). Our objective is to determine
      1) whether renal arginase activity or expression is increased in renal IRI, and
      2) whether arginase plays a role in development of renal IRI. The impact of
      arginase activity and expression on renal damage was evaluated in male C57BL/6J
      (wild type) and arginase-2 (ARG2)-deficient (Arg2-/- ) mice subjected to
      bilateral renal ischemia for 28 min, followed by reperfusion for 24 h. ARG2
      expression and arginase activity significantly increased following renal IRI,
      paralleling the increase in kidney injury. Pharmacological blockade or genetic
      deficiency of Arg2 conferred kidney protection in renal IRI. Arg2-/- mice had
      significantly attenuated kidney injury and lower plasma creatinine and blood urea
      nitrogen levels after renal IRI. Blocking arginases using S-(2-boronoethyl)-l
      cysteine (BEC) 18 h before ischemia mimicked arginase deficiency by reducing
      kidney injury, histopathological changes and kidney injury marker-1 expression,
      renal apoptosis, kidney inflammatory cell recruitment and inflammatory cytokines,
      and kidney oxidative stress; increasing kidney nitric oxide (NO) production and
      endothelial NO synthase (eNOS) phosphorylation, kidney peroxisome proliferator
      activated receptor-gamma coactivator-1alpha expression, and mitochondrial ATP;
      and preserving kidney mitochondrial ultrastructure compared with vehicle-treated
      IRI mice. Importantly, BEC-treated eNOS-knockout mice failed to reduce blood urea
      nitrogen and creatinine following renal IRI. These findings indicate that ARG2
      plays a major role in renal IRI, via an eNOS-dependent mechanism, and that
      blocking ARG2 activity or expression could be a novel therapeutic approach for
      prevention of AKI.

PMID- 28515182
TI  - Health assets in older age: a systematic review.
AB  - BACKGROUND: Finding ways to optimise health in older age is key to reducing the
      impact of population ageing on health and social care systems. A salutogenic
      approach takes into account an individual's health assets-internal or external
      strengths or accessible resources which improve and preserve physical, social and
      mental wellness, independence and quality of life. The aim of this narrative
      systematic review was to provide a summary and appraisal of the evidence for
      factors that act as health assets within personal, social, economic and
      environmental domains. METHODS: Systematic searches of databases were conducted
      for literature published in peer-reviewed journals between January 2000 and
      November 2016. Selection criteria included community dwelling populations aged 65
      years and over and publications written in English. Data on study population,
      design, measures of health status, factors within the four previously stated
      domains and results were extracted. Study quality was independently assessed
      using an appraisal instrument. RESULTS: Twenty-three publications, including 78
      422 participants, from more than 13 different countries were identified for
      inclusion in this review. There was strong evidence that higher scores of self
      rated health, psychological well-being and life satisfaction were associated with
      better health in older age. Social network and contact with family and friends,
      and engagement in leisure and social activities were important support
      mechanisms. Education and financial resources consistently proved to be key
      economic health assets for older adults. CONCLUSIONS: Implementing an asset-based
      approach to health promotion uncovers the skills, knowledge, connections and
      potential of the individual and the community. This approach is an ideal
      opportunity for government health bodies and their partners to respond to the
      challenges faced by global ageing.Factors are often interdependent and
      cumulative, suggesting the potential for an instrument to measure the accumulated
      effect of health assets on health status in older adults.

PMID- 28515183
TI  - Modeling lifetime costs and health outcomes attributable to secondhand smoke
      exposure at home among Korean adult women.
AB  - PURPOSE: The aim of this research is to estimate lifetime costs and health
      consequences for Korean adult women who were exposed to secondhand smoke (SHS) at
      home. METHODS: A Markov model was developed to project the lifetime healthcare
      costs and health outcomes of a hypothetical cohort of Korean women who are 40
      years old and were married to current smokers. The Korean epidemiological data
      were used to reflect the natural history of SHS-exposed and non-exposed women.
      The direct healthcare costs (in 2014 US dollars) and quality-adjusted life years
      (QALYs) were annually discounted at 5% to reflect time preference. The time
      horizon of the analysis was lifetime and the cycle length was 1 year.
      Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In
      the absence of SHS exposure, Korean women will live 41.32 years or 34.56 QALYs
      before discount, which corresponded to 17.29 years or 15.35 QALYs after discount.
      The SHS-exposed women were predicted to live 37.91 years and 31.08 QALYs before
      discount and 16.76 years and 14.62 QALYs after discount. The estimated lifetime
      healthcare cost per woman in the SHS non-exposed group was US$11 214 before the
      discount and US$2465 after discount. The negative impact of SHS exposure on
      health outcomes and healthcare costs escalated as the time horizon increased,
      suggesting that the adverse impact of SHS exposure may have higher impact on the
      later part of the lifetime. The result was consistent across a wide range of
      assumptions. CONCLUSION: Life expectancy might underestimate the impact of SHS
      exposure on health outcomes, especially if the time horizon of the analysis is
      not long enough. Early intervention on smoking behaviour could substantially
      reduce direct healthcare costs and improve quality of life attributable to SHS
      exposure.

PMID- 28515184
TI  - Trends and population-attributable risk estimates for predictors of early
      neonatal mortality in Nigeria, 2003-2013: a cross-sectional analysis.
AB  - OBJECTIVES: To assess trends in early neonatal mortality (ENM) and population
      attributable risk (PAR) estimates for predictors of ENM in Nigeria. DESIGN,
      SETTING AND PARTICIPANTS: A cross-sectional data on 63 844 singleton live births
      within the preceding 5 years from the 2003, 2008 and 2013 Nigeria Demographic and
      Health Surveys were used. Adjusted PARs were used to estimate the number of early
      neonatal deaths attributable to each predictor in the final multivariable Cox
      regression model. MAIN OUTCOME MEASURES: ENM, defined as the death of a live-born
      singleton between birth and 6 days of life. RESULTS: The ENM rate slightly
      declined from 30.5 (95% CI 26.1 to 34.9) to 26.1 (CI 24.3 to 27.9) during the
      study period. Approximately 36 746 (CI 14 656 to 56 920) and 37 752 (CI 23 433 to
      51 126) early neonatal deaths were attributable to rural residence and male sex,
      respectively. Other significant predictors of ENM included small neonates
      (attributable number: 25 884, CI 19 172 to 31 953), maternal age <20 years (11
      708, CI 8521 to 17 042), caesarean section (6312, CI 4260 to 8521) and birth
      order >=4 with a short birth interval (<=2 years) (18 929, CI 12 781 to 25 563)).
      CONCLUSIONS: To improve early neonatal survival in Nigeria, community-based
      interventions are needed for small neonates, and to promote delayed first
      pregnancy, child spacing and timely referral for sick male neonates and caesarean
      delivery.

PMID- 28515185
TI  - The job content questionnaire in various occupational contexts: applying a latent
      class model.
AB  - OBJECTIVE: To evaluate Job Content Questionnaire(JCQ) performance using the
      latent class model. METHODS: We analysed cross-sectional studies conducted in
      Brazil and examined three occupational categories: petroleum industry workers
      (n=489), teachers (n=4392) and primary healthcare workers (3078)and 1552 urban
      workers from a representative sample of the city of Feira de Santana in Bahia,
      Brazil. An appropriate number of latent classes was extracted and described each
      occupational category using latent class analysis, a multivariate method that
      evaluates constructs and takes into accountthe latent characteristics underlying
      the structure of measurement scales. The conditional probabilities of workers
      belonging to each class were then analysed graphically. RESULTS: Initially, the
      latent class analysis extracted four classes corresponding to the four job types
      (active, passive, low strain and high strain) proposed by the Job-Strain model
      (JSM) and operationalised by the JCQ. However, after taking into consideration
      the adequacy criteria to evaluate the number of extracted classes, three classes
      (active, low strain and high strain) were extracted from the studies of urban
      workers and teachers and four classes (active, passive, low strain and high
      strain) from the study of primary healthcare and petroleum industry workers.
      CONCLUSION: The four job types proposed by the JSM were identified among primary
      healthcare and petroleum industry workers-groups with relatively high levels of
      skill discretion and decision authority. Three job types were identified for
      teachers and urban workers; however, passive job situations were not found within
      these groups. The latent class analysis enabled us to describe the conditional
      standard responses of the job types proposed by the model, particularly in
      relation to active jobs and high and low strain situations.

PMID- 28515186
TI  - Understanding determinants of unequal distribution of stillbirth in Tehran, Iran:
      a concentration index decomposition approach.
AB  - OBJECTIVE: The present inquiry set to determine the economic inequality in
      history of stillbirth and understanding determinants of unequal distribution of
      stillbirth in Tehran, Iran. METHODS: A population-based cross-sectional study was
      conducted on 5170 pregnancies in Tehran, Iran, since 2015. Principal component
      analysis (PCA) was applied to measure the asset-based economic status.
      Concentration index was used to measure socioeconomic inequality in stillbirth
      and then decomposed into its determinants. RESULTS: The concentration index and
      its 95% CI for stillbirth was -0.121 (-0.235 to -0.002). Decomposition of the
      concentration index showed that mother's education (50%), mother's occupation
      (30%), economic status (26%) and father's age (12%) had the highest positive
      contributions to measured inequality in stillbirth history in Tehran. Mother's
      age (17%) had the highest negative contribution to inequality. CONCLUSIONS:
      Stillbirth is unequally distributed among Iranian women and is mostly
      concentrated among low economic status people. Mother-related factors had the
      highest positive and negative contributions to inequality, highlighting specific
      interventions for mothers to redress inequality.

PMID- 28515188
TI  - Trends in socioeconomic inequalities in five major risk factors for
      cardiovascular disease in the Korean population: a cross-sectional study using
      data from the Korea National Health and Nutrition Examination Survey, 2001-2014.
AB  - OBJECTIVES: To examine trends in socioeconomic inequalities in major
      cardiovascular disease (CVD) risk factors among the Korean population. DESIGN:
      Cross-sectional study. SETTING: A nationally representative population survey
      database. PARTICIPANTS: A total of 42 725 Koreans, aged 25-64 years, who
      participated in the Korean National Health and Nutrition Examination Survey
      (KNHANES) II (2001) to VI (2013-2014). MAIN OUTCOME MEASURES: Trends in
      socioeconomic inequalities in five major CVD risk factors (smoking, obesity,
      diabetes, hypertension and hypercholesterolaemia). RESULTS: Gender differences
      were noted in the time trends in socioeconomic inequalities in smoking, obesity,
      diabetes and hypertension. Among men, low socioeconomic status (SES) was
      associated with higher prevalence of smoking, but not with obesity, diabetes or
      hypertension. The magnitudes of socioeconomic inequalities in smoking, obesity
      and diabetes remained unchanged, and the magnitude of the inequality in
      hypertension decreased over time. However, among women, low SES was associated
      with higher prevalence of smoking, obesity, diabetes and hypertension. Time
      trends towards increasing socioeconomic inequalities, measured by income, in
      smoking, obesity and diabetes were found in women. Unlike the other CVD risk
      factors, hypercholesterolaemia was not associated with socioeconomic inequality.
      CONCLUSIONS: SES had a stronger impact on major CVD risk factors among Korean
      women than men. Moreover, socioeconomic inequalities in smoking, obesity and
      diabetes worsened among Korean women over time. Public policies to prevent
      smoking, obesity and diabetes in women with lower SES are needed to address
      inequalities.

PMID- 28515187
TI  - Reducing social isolation and loneliness in older people: a systematic review
      protocol.
AB  - INTRODUCTION: Social isolation and loneliness affect approximately one-third to
      one-half of the elderly population and have a negative impact on their physical
      and mental health. Group-based interventions where facilitators are well trained
      and where the elderly are actively engaged in their development seem to be more
      effective, but conclusions have been limited by weak study designs. We aim to
      conduct a systematic review to assess the effectiveness of health promotion
      interventions on social isolation or loneliness in older people. METHODS AND
      ANALYSIS: A systematic review was conducted in Medline, Embase, PsycINFO,
      Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences
      Index and Abstracts, LILACS, OpenGrey and the Cochrane Library on peer-reviewed
      studies and doctoral theses published between 1995 and 2016 evaluating the impact
      of health promotion interventions on social isolation and/or loneliness for
      individuals aged 60 and over. Two reviewers will independently assess each study
      for inclusion and disagreements will be resolved by a third reviewer. Data will
      be extracted using a predefined pro forma following best practice. Study quality
      will be assessed with the Effective Public Health Practice Project quality
      assessment tool. A narrative synthesis of all studies will be presented by type
      of outcome (social isolation or loneliness) and type of intervention. If
      feasible, the effectiveness data will be synthesised using appropriate
      statistical techniques. ETHICS AND DISSEMINATION: This systematic review is
      exempt from ethics approval because the work is carried out on published
      documents. The findings of the review will be disseminated in a related peer
      reviewed journal and presented at conferences. They will also contribute to a
      DPhil thesis. TRIAL REGISTRATION NUMBER: CRD42016039650.

PMID- 28515189
TI  - 10-year trends in statin utilization in Taiwan: a retrospective study using
      Taiwan's National Health Insurance Research Database.
AB  - OBJECTIVE: Statins have been commonly used to treat patients with
      hypercholesterolaemia and to prevent cardiovascular disease (CVD) worldwide. This
      study examined trends in use of statins in Taiwan from 2002 to 2011. DESIGN: This
      is a retrospective observational study focusing on the utilisation of statins.
      SETTING: The monthly claims data for statins between 2002 and 2011 were retrieved
      from Taiwan's National Health Insurance Research Database. MAIN OUTCOME MEASURES:
      We calculated the yearly prescription rate per new user for each statin. Products
      were classified as high-intensity/moderate-intensity/low-intensity statins by
      type of statin and dosage. Users were also classified based on disease histories.
      RESULTS: The number of statin users increased from 10 299 (~1.4% of adults) in
      2002 to 50 687 (~6.3% of adults) in 2011. Atorvastatin was the most commonly used
      agent (28.4%-36.7%) during the study period. After 2007, simvastatin ranked
      second with 21.7% market share, followed by rosuvastatin, a newer agent that
      exhibited a substantial growth in prescription rates (3.4% in 2005 and 19.5% in
      2011). In 2011, 94.0% of new statin users used statin monotherapies, and 6.0%
      used combination therapies. Use of moderate-intensity statins increased from
      49.0% in 2002 to 71.0% in 2011, while high-intensity statins remained low.
      Patients with history of coronary events or cerebrovascular events were more
      likely to be prescribed higher intensity statins compared with those without.
      Prescribing of higher intensity statins was not greater among people with
      diabetes compared with those without during 2007-2011. Selection of statins did
      not differ between people with versus without history of myopathy or liver
      injury. CONCLUSION: Atorvastatin was the most commonly used statin in Taiwan
      during 2002-2011. While patients with history of CVD were more likely to be
      prescribed higher intensity statins compared with those without, this difference
      was not found comparing those with and without diabetes.

PMID- 28515191
TI  - Socially disparate trends in lifespan variation: a trend study on income and
      mortality based on nationwide Danish register data.
AB  - BACKGROUND: Social inequality trends in life expectancy are not informative as to
      changes in social disparity in the age-at-death distribution. The purpose of the
      study was to investigate social differentials in trends and patterns of adult
      mortality in Denmark. METHODS: Register data on income and mortality from 1986 to
      2014 were used to investigate trends in life expectancy, life disparity and the
      threshold age that separates 'premature' and 'late' deaths. Mortality compression
      was quantified and compared between income quartiles. RESULTS: Since 1986, male
      life expectancy increased by 4.2 years for the lowest income quartile and by 8.4
      years for the highest income quartile. The clear compression of mortality
      apparent in the highest income quartile did not occur for the lowest income
      quartile. Premature and late deaths accounted both by 2.1 years of the increase
      in life expectancy in the lowest income quartile and by 6.0 and 2.4 years,
      respectively, in the highest income quartile. Life expectancy increased by 5.2
      years among women in the lowest income quartile, 2.4 years due to premature
      deaths and 2.8 years due to late deaths. The gain in life expectancy among women
      in the highest income quartile of 5.6 years was distributed by 5.0 and 0.6 years
      due to premature and late deaths, respectively. CONCLUSION: The study
      demonstrates that the increasing social gap in mortality appears differently in
      the change of the age-at-death distribution. Thus, no compression of mortality
      was seen in the lowest income quartile. The results do not provide support for a
      uniformly extension of pension age for all.

PMID- 28515192
TI  - Study protocol for a transversal study to develop a screening model for excessive
      gambling behaviours on a representative sample of users of French authorised
      gambling websites.
AB  - INTRODUCTION: Since the legalisation of online gambling in France in 2010,
      gambling operators must implement responsible gambling measures to prevent
      excessive gambling practices. However, actually there is no screening procedure
      for identifying problematic gamblers. Although several studies have already been
      performed using several data sets from online gambling operators, the authors
      deplored several methodological and clinical limits that prevent scientifically
      validating the existence of problematic gambling behaviour. The aim of this study
      is to develop a model for screening excessive gambling practices based on the
      gambling behaviours observed on French gambling websites, coupled with a clinical
      validation. METHODS AND ANALYSIS: The research is divided into three successive
      stages. All analyses will be performed for each major type of authorised online
      gambling in France. The first stage aims at defining a typology of users of
      French authorised gambling websites based on their gambling behaviour. This
      analysis will be based on data from the Authority for Regulating Online Gambling
      (ARJEL) and the Francaise Des Jeux (FDJ). For the second stage aiming at
      determining a score to predict whether a gambler is problematic or not, we will
      cross answers from the Canadian Problem Gambling Index with real gambling data.
      The objective of the third stage is to clinically validate the score previously
      developed. Results from the screening model will be compared (using sensitivity,
      specificity, area under the curve, and positive and negative predictive values)
      with the diagnosis obtained with a telephone clinical interview, including
      diagnostic criteria for gambling addiction. ETHICS AND DISSEMINATION: This study
      was approved by the local Research Ethics Committee (GNEDS) on 25 March 2015.
      Results will be presented in national and international conferences, submitted to
      peer-reviewed journals and will be part of a PhD thesis. A final report with the
      study results will be presented to the ARJEL, especially the final screening
      model. TRIAL REGISTRATION NUMBER: NCT02415296.

PMID- 28515190
TI  - Interaction of ACE genotype and salt intake on hypertension among Chinese
      Kazakhs: results from a population-based cross-sectional study.
AB  - OBJECTIVES: To explore the effect of interaction between ACE genotype and salt
      intake on hypertension among Chinese Kazakhs, and to compare applications of
      interactions between logistic model and generalised partially linear tree-based
      regression (GPLTR) model. DESIGN: Population-based cross-sectional study.
      SETTING: Hong Dun, North Xinjiang, China. PARTICIPANTS: Non-consanguineous
      Chinese Kazakh participants (n=916, 342 men and 574 women) aged >=30 years. MAIN
      OUTCOME MEASURES: Association between ACE genotype and hypertension, association
      between salt intake and hypertension, and interaction of ACE genotype and salt
      intake on hypertension in two models. RESULTS: Associations between salt intake
      and hypertension were different in ACE genotype of II and ID+DD. Under the
      logistic models, main and interaction effects were not observed for men, but
      effects were present in opposite directions for women (main effect of ACE:
      OR=0.20, p=0.003; interaction effect: OR=1.07, p=0.027). Under the GPLTR model,
      Bayesian information criterion trees included both salt intake and ACE genotype
      as split variables. Individuals with a salt intake >=19.5 g/day and ID+DD
      genotypes had a 3.99-fold (p=0.004) higher risk of hypertension compared with the
      II genotype for men, whereas salt intake <20.1 g/day and ID+DD genotypes had an
      OR=0.55 (p=0.014) compared with the II genotype for women. CONCLUSIONS: An
      interaction of ACE genotype and salt intake on hypertension was observed among
      Chinese Kazakhs but in different ways according to sex. The GPLTR model appears
      to be more suitable for an exploration of interactions in complex diseases.

PMID- 28515193
TI  - Cost-effectiveness of telehealthcare to patients with chronic obstructive
      pulmonary disease: results from the Danish 'TeleCare North' cluster-randomised
      trial.
AB  - OBJECTIVES: To investigate the cost-effectiveness of a telehealthcare solution in
      addition to usual care compared with usual care. DESIGN: A 12-month cost-utility
      analysis conducted alongside a cluster-randomised trial. SETTING: Community-based
      setting in the geographical area of North Denmark Region in Denmark.
      PARTICIPANTS: 26 municipality districts define randomisation clusters with 13
      districts in each arm. 1225 patients with chronic obstructive pulmonary disease
      were enrolled, of which 578 patients were randomised to telehealthcare and 647 to
      usual care. INTERVENTIONS: In addition to usual care, patients in the
      intervention group received a set of telehealthcare equipment and were monitored
      by a municipality-based healthcare team. Patients in the control group received
      usual care. MAIN OUTCOME MEASURE: Incremental costs per quality-adjusted life
      years gained from baseline up to 12 months follow-up. RESULTS: From a healthcare
      and social sector perspective, the adjusted mean difference in total costs
      between telehealthcare and usual care was ?728 (95% CI -754 to 2211) and the
      adjusted mean difference in quality-adjusted life-years gained was 0.0132 (95% CI
      -0.0083 to 0.0346). The incremental cost-effectiveness ratio was ?55 327 per
      quality-adjusted life-year gained. Decision-makers should be willing to pay more
      than ?55 000 to achieve a probability of cost-effectiveness >50%. This conclusion
      is robust to changes in the definition of hospital contacts and reduced
      intervention costs. Only in the most optimistic scenario combining the effects of
      all sensitivity analyses, does the incremental cost-effectiveness ratio fall
      below the UK thresholds values (?21 068 per quality-adjusted life-year).
      CONCLUSIONS: Telehealthcare is unlikely to be a cost-effective addition to usual
      care, if it is offered to all patients with chronic obstructive pulmonary disease
      and if the willingness-to-pay threshold values from the National Institute for
      Health and Care Excellence are applied. TRIAL REGISTRATION: Clinicaltrials.gov,
      NCT01984840, 14 November 2013.

PMID- 28515194
TI  - Do patients and health care providers have discordant preferences about which
      aspects of treatments matter most? Evidence from a systematic review of discrete
      choice experiments.
AB  - OBJECTIVES: To review studies eliciting patient and healthcare provider
      preferences for healthcare interventions using discrete choice experiments (DCEs)
      to (1) review the methodology to evaluate similarities, differences, rigour of
      designs and whether comparisons are made at the aggregate level or account for
      individual heterogeneity; and (2) quantify the extent to which they demonstrate
      concordance of patient and healthcare provider preferences. METHODS: A systematic
      review searching Medline, EMBASE, Econlit, PsycINFO and Web of Science for DCEs
      using patient and healthcare providers. INCLUSION CRITERIA: peer-reviewed;
      complete empiric text in English from 1995 to 31July 2015; discussing a
      healthcare-related topic; DCE methodology; comparing patients and healthcare
      providers. DESIGN: Systematic review. RESULTS: We identified 38 papers exploring
      16 interventions in 26 diseases/indications. Methods to analyse results,
      determine concordance between patient and physician values, and explore
      heterogeneity varied considerably between studies. The majority of studies we
      reviewed found more evidence of mixed concordance and discordance (n=28) or
      discordance of patient and healthcare provider preferences (n=12) than of
      concordant preferences (n=4). A synthesis of concordance suggested that
      healthcare providers rank structure and outcome attributes more highly than
      patients, while patients rank process attributes more highly than healthcare
      providers. CONCLUSIONS: Discordant patient and healthcare provider preferences
      for different attributes of healthcare interventions are common. Concordance
      varies according to whether attributes are processes, structures or outcomes, and
      therefore determining preference concordance should consider all aspects jointly
      and not a binary outcome. DCE studies provide excellent opportunities to assess
      value concordance between patients and providers, but assessment of concordance
      was limited by a lack of consistency in the approaches used and consideration of
      heterogeneity of preferences. Future DCEs assessing concordance should fully
      report the framing of the questions and investigate the heterogeneity of
      preferences within groups and how these compare.

PMID- 28515197
TI  - Models for estimating and projecting global, regional and national prevalence and
      disease burden of asthma: protocol for a systematic review.
AB  - INTRODUCTION: Models that have so far been used to estimate and project the
      prevalence and disease burden of asthma are in most cases inadequately described
      and irreproducible. We aim systematically to describe and critique the existing
      models in relation to their strengths, limitations and reproducibility, and to
      determine the appropriate models for estimating and projecting the prevalence and
      disease burden of asthma. METHODS: We will search the following electronic
      databases to identify relevant literature published from 1980 to 2017: Medline,
      Embase, WHO Library and Information Services and Web of Science Core Collection.
      We will identify additional studies by searching the reference list of all the
      retrieved papers and contacting experts. We will include observational studies
      that used models for estimating and/or projecting prevalence and disease burden
      of asthma regarding human population of any age and sex. Two independent
      reviewers will assess the studies for inclusion and extract data from included
      papers. Data items will include authors' names, publication year, study aims,
      data source and time period, study population, asthma outcomes, study
      methodology, model type, model settings, study variables, methods of model
      derivation, methods of parameter estimation and/or projection, model fit
      information, key findings and identified research gaps. A detailed critical
      narrative synthesis of the models will be undertaken in relation to their
      strengths, limitations and reproducibility. A quality assessment checklist and
      scoring framework will be used to determine the appropriate models for estimating
      and projecting the prevalence anddiseaseburden of asthma. ETHICS AND
      DISSEMINATION: We will not collect any primary data for this review, and hence
      there is no need for formal National Health Services Research Ethics Committee
      approval. We will present our findings at scientific conferences and publish the
      findings in the peer-reviewed scientific journal.

PMID- 28515196
TI  - Cost-effectiveness of therapist-guided internet-delivered cognitive behaviour
      therapy for paediatric obsessive-compulsive disorder: results from a randomised
      controlled trial.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of a therapist-guided internet
      delivered cognitive behaviour therapy (ICBT) intervention for adolescents with
      obsessive-compulsive disorder (OCD) compared with untreated patients on a
      waitlist. DESIGN: Single-blinded randomised controlled trial. SETTING: A research
      clinic within the regular child and adolescent mental health service in
      Stockholm, Sweden. PARTICIPANTS: Sixty-seven adolescents (12-17 years) with a
      Diagnostic and Statistical Manual of Mental Disorders Fifth Edition diagnosis of
      OCD. INTERVENTIONS: Either a 12-week, therapist-guided ICBT intervention or a
      wait list condition of equal duration. PRIMARY OUTCOME MEASURES: Cost data were
      collected at baseline and after treatment, including healthcare use, supportive
      resources, prescription drugs, prescription-free drugs, school absence and
      productivity loss, as well as the cost of ICBT. Health outcomes were defined as
      treatment responder rate and quality-adjusted life years gain. Bootstrapped mixed
      model analyses were conducted comparing incremental costs and health outcomes
      between the groups from the societal and healthcare perspectives. RESULTS:
      Compared with waitlist control, ICBT generated substantial societal cost savings
      averaging US$-144.98 (95% CI -159.79 to -130.16) per patient. The cost reductions
      were mainly driven by reduced healthcare use in the ICBT group. From the societal
      perspective, the probability of ICBT being cost saving compared with waitlist
      control was approximately 60%. From the healthcare perspective, the cost per
      additional responder to ICBT compared with waitlist control was approximately
      US$78. CONCLUSIONS: The results suggest that therapist-guided ICBT is a cost
      effective treatment and results in societal cost savings, compared with patients
      who do not receive evidence-based treatment. Since, at present, most patients
      with OCD do not have access to evidence-based treatments, the results have
      important implications for the increasingly strained national and healthcare
      budgets. Future studies should compare the cost-effectiveness of ICBT with
      regular face-to-face CBT. TRIAL REGISTRATION NUMBER: NCT02191631.

PMID- 28515195
TI  - Cohort profile: internal migration in sub-Saharan Africa-The Migration and Health
      in Malawi (MHM) study.
AB  - PURPOSE: The Migration and Health in Malawi (MHM) study focuses on a key
      challenge in migration research: although it has long been established that
      migration and health are closely linked, identifying the effect of migration on
      various health outcomes is complicated by methodological challenges. The MHM
      study uses a longitudinal panel premigration and postmigration study design (with
      a non-migrant comparison group) to measure and/or control for important
      characteristics that affect both migration and health outcomes. PARTICIPANTS:
      Data are available for two waves. The MHM interviewed 398 of 715 migrants in 2007
      (55.7%) and 722 of 1013 in 2013 (71.3%); as well as 604 of 751 (80.4%) for a non
      migrant reference group in 2013. The total interviewed sample size for the MHM in
      both waves is 1809. These data include extensive information on lifetime
      migration, socioeconomic and demographic characteristics, sexual behaviours,
      marriage, household/family structure, social networks and social capital,
      HIV/AIDS biomarkers and other dimensions of health. FINDINGS TO DATE: Our result
      for the relationship between migration and health differs by health measure and
      analytic approach. Migrants in Malawi have a significantly higher HIV prevalence
      than non-migrants, which is primarily due to the selection of HIV-positive
      individuals into migration. We find evidence for health selection; physically
      healthier men and women are more likely to move, partly because migration selects
      younger individuals. However, we do not find differences in physical or mental
      health between migrants and non-migrants after moving. FUTURE PLANS: We are
      preparing a third round of data collection for these (and any new) migrants,
      which will take place in 2018. This cohort will be used to examine the effect of
      migration on various health measures and behaviours, including general mental and
      physical health, smoking and alcohol use, access to and use of health services
      and use of antiretroviral therapy.

PMID- 28515198
TI  - Post-authorisation passive enhanced safety surveillance of seasonal influenza
      vaccines: protocol of a pilot study in England.
AB  - AIM: To pilot enhanced safety surveillance of seasonal influenza vaccine meeting
      the European Medicines Agency (EMA) requirement to rapidly detect a significant
      increase in the frequency or severity of adverse events of interest (AEIs), which
      may indicate risk from the new season's vaccine. STUDY DESIGN: A prospective
      passive enhanced safety surveillance combining data collection from adverse drug
      reaction (ADR) cards with automated collection of pseudonymised routinely
      collected electronic health record (EHR) data. This study builds on a feasibility
      study carried out at the start of the 2015/2016 influenza season. We will report
      influenza vaccine exposure and any AEIs reported via ADR card or recorded
      directly into the EHR, from the commencement of influenza vaccination and ends as
      specified by EMA (30 November 2016). SETTING: Ten volunteer English general
      practices, primarily using the GSK influenza vaccines. They had selected this
      vaccine in advance of the study. PARTICIPANTS: People who receive a seasonal
      influenza vaccine, in each age group defined in EMA interim guidance: 6 months to
      5 years, 6-12 years, 13-17 years, 18-65 years and >65 years. OUTCOME MEASURES:
      The primary outcome measure is the rate of AEIs occurring within 7 days
      postvaccination, using passive surveillance of general practitioner (GP) EHR
      systems enhanced by a card-based ADR reporting system. Extracted data will be
      presented overall by brand (Fluarix Tetra vs others), by age strata and risk
      groups. The secondary outcome measure is the vaccine uptake among the subjects
      registered in the enrolled general practices. ETHICS AND DISSEMINATION: Ethical
      approval was granted by the Proportionate Review Sub-committee of the North East
      Newcastle & North Tyneside 2 on 5 August 2016. The study received approval from
      the Health Research Authority on 1 September 2016. We will produce an interim
      analysis within 8 weeks, and an end-of-study report, which will be submitted to
      peer-reviewed journals.

PMID- 28515199
TI  - Are healthcare aides underused in long-term care? A cross-sectional study on
      continuing care facilities in Canada.
AB  - OBJECTIVES: Over the last 10 years, appropriate workforce utilisation has been an
      important discussion among healthcare practitioners and policy-makers. The role
      of healthcare aides (HCAs) has also expanded to improve their utilisation. This
      evolving role of HCAs in Canada has prompted calls for standardised training,
      education and scope of practice for HCAs. The purpose of this research was to
      examine the differences in HCAs training and utilisation in continuing care
      facilities. DESIGN: From June 2014 to July 2015, we conducted a mixed-method
      study on HCA utilisation in continuing care. This paper presents findings
      gathered solely from the prospective cross-sectional survey of continuing care
      facilities (long-term care (LTC) and supportive living (SL)) on HCA utilisation.
      SETTING AND PARTICIPANTS: We conducted this study in a Western Canadian province.
      The managers of the continuing care facilities (SL and LTC) were eligible to
      participate in the survey. PRIMARY OUTCOME MEASURES: The pattern of HCAs
      involvement in medication assistance and other care activities in SL and LTC
      facilities. RESULTS: We received 130 completed surveys (LTC=64 and SL=52). Our
      findings showed that approximately 81% of HCAs were fully certified. We found
      variations in how HCAs were used in SL and LTC facilities. Overall, HCAs in SL
      were more likely to be involved in medication management such as assisting with
      inhaled medication and oral medication delivery. A significantly larger
      proportion of survey respondents from SL facilities reported that medication
      assistance training was mandatory for their HCAs (86%) compared with the LTC
      facilities (50%) (p value <0.01). CONCLUSION: The utilisation of HCAs varies
      widely between SL and LTC facilities. HCAs in SL facilities may be considered
      better used according to their required educational training and competencies.
      Expanding the role of HCAs in LTC facilities may lead to a cost-effective and
      more efficient utilisation of workforce in continuing care facilities.

PMID- 28515200
TI  - Impact of expedited partner therapy (EPT) implementation on chlamydia incidence
      in the USA.
AB  - OBJECTIVES: The diagnosis and treatment of Chlamydia trachomatis infection is
      important in preventing persistent or recurrent infection. Expedited partner
      therapy (EPT) is the favoured and supported method for STI treatment of the
      Centers for Disease Control and Prevention when the provider cannot be assured
      that all recent sexual partner(s) will seek therapy. EPT is legally permissible
      in 38 states and is endorsed by healthcare organisations to decrease the rates of
      chlamydia and gonorrhoea infection. Our study investigated the impact of EPT
      legal status (permissible, potentially allowable or prohibited) on C. trachomatis
      infection rates for each state. METHODS: Our ecological study modelled the number
      of reported chlamydia cases from 2000 to 2013 as a function of year, legal status
      and the interaction between year and legality. We used a negative binomial
      regression model that included state fixed effects (including the District of
      Columbia) to account for both the repeated measures per state and state-specific
      characteristics that could not be measured for inclusion in this study. The
      lagged number of C. trachomatis cases was included as a covariate and each
      state's total population for a given year was included in the model as an
      exposure parameter. States were designated Y (EPT permissible), N (EPT
      prohibited) and M (EPT potentially allowable), and the legal status of each state
      could vary over time. RESULTS: Each legal category saw an increase in the
      incidence rate of C. trachomatis infection, but on average, the incidence rate
      for states with prohibitive EPT legislation grew significantly faster over time
      compared with the rate for the states where EPT was permissible. The average
      increase in predicted incidence rates per year for states with Y, N and M legal
      status were 14.1 (95% CI (12.0 to 16.2)), 17.5 (95% CI (15.9 to 19.2)) and 16.8
      (95% CI (15.0 to 18.6)) cases per 100 000 persons per year, respectively, when
      controlling for state-specific effects. CONCLUSIONS: Our model suggests that a
      lack of EPT legislation is associated with an increase in STI rates. States with
      potentially allowable EPT legislation as of 2013 (n=8) should consider permitting
      EPT as a component of a multipronged strategy for treatment of sexual partners to
      prevent C. trachomatis infection.

PMID- 28515201
TI  - Pre- versus post-mass extinction divergence of Mesozoic marine reptiles dictated
      by time-scale dependence of evolutionary rates.
AB  - The fossil record of a major clade often starts after a mass extinction even
      though evolutionary rates, molecular or morphological, suggest its pre-extinction
      emergence (e.g. squamates, placentals and teleosts). The discrepancy is larger
      for older clades, and the presence of a time-scale-dependent methodological bias
      has been suggested, yet it has been difficult to avoid the bias using Bayesian
      phylogenetic methods. This paradox raises the question of whether ecological
      vacancies, such as those after mass extinctions, prompt the radiations. We
      addressed this problem by using a unique temporal characteristic of the
      morphological data and a high-resolution stratigraphic record, for the oldest
      clade of Mesozoic marine reptiles, Ichthyosauromorpha. The evolutionary rate was
      fastest during the first few million years of ichthyosauromorph evolution and
      became progressively slower over time, eventually becoming six times slower.
      Using the later slower rates, estimates of divergence time become excessively
      older. The fast, initial rate suggests the emergence of ichthyosauromorphs after
      the end-Permian mass extinction, matching an independent result from high
      resolution stratigraphic confidence intervals. These reptiles probably invaded
      the sea as a new ecosystem was formed after the end-Permian mass extinction. Lack
      of information on early evolution biased Bayesian clock rates.

PMID- 28515202
TI  - Does coevolution with a shared parasite drive hosts to partition their defences
      among species?
AB  - When mimicry imposes costs on models, selection may drive the model's phenotype
      to evolve away from its mimic. For example, brood parasitism often drives hosts
      to diversify in egg appearance among females within a species, making mimetic
      parasitic eggs easier to detect. However, when a single parasite species exploits
      multiple host species, parasitism could also drive host egg evolution away from
      other co-occurring hosts, to escape susceptibility to their respective mimics.
      This hypothesis predicts that sympatric hosts of the same parasite should
      partition egg phenotypic space (defined by egg colour, luminance and pattern)
      among species to avoid one another. We show that eggs of warbler species
      parasitized by the cuckoo finch Anomalospiza imberbis in Zambia partition
      phenotypic space much more distinctly than do eggs of sympatric but unparasitized
      warblers. Correspondingly, cuckoo finch host-races better match their own
      specialist host than other local host species. In the weaver family, parasitized
      by the diederik cuckoo Chrysococcyx caprius, by contrast, parasitized species
      were more closely related and overlapped extensively in phenotypic space;
      correspondingly, cuckoos did not match their own host better than others. These
      results suggest that coevolutionary arms races between hosts and parasites may be
      shaped by the wider community context in which they unfold.

PMID- 28515203
TI  - Wild birds respond to flockmate loss by increasing their social network
      associations to others.
AB  - Understanding the consequences of losing individuals from wild populations is a
      current and pressing issue, yet how such loss influences the social behaviour of
      the remaining animals is largely unexplored. Through combining the automated
      tracking of winter flocks of over 500 wild great tits (Parus major) with removal
      experiments, we assessed how individuals' social network positions responded to
      the loss of their social associates. We found that the extent of flockmate loss
      that individuals experienced correlated positively with subsequent increases in
      the number of their social associations, the average strength of their bonds and
      their overall connectedness within the social network (defined as summed edge
      weights). Increased social connectivity was not driven by general disturbance or
      changes in foraging behaviour, but by modifications to fine-scale social network
      connections in response to losing their associates. Therefore, the reduction in
      social connectedness expected by individual loss may be mitigated by increases in
      social associations between remaining individuals. Given that these findings
      demonstrate rapid adjustment of social network associations in response to the
      loss of previous social ties, future research should examine the generality of
      the compensatory adjustment of social relations in ways that maintain the
      structure of social organization.

PMID- 28515204
TI  - A genetic legacy of introgression confounds phylogeny and biogeography in oaks.
AB  - Oaks (Quercus L.) have long been suspected to hybridize in nature, and widespread
      genetic exchange between morphologically defined species is well documented in
      two- to six-species systems, but the phylogenetic consequences of hybridization
      in oaks have never been demonstrated in a phylogenetically diverse sample. Here,
      we present phylogenomic analyses of a ca 30 Myr clade that strongly support
      morphologically defined species and the resolution of novel clades of white oaks;
      however, historical hybridization across clade boundaries is detectable and,
      undiagnosed, would obscure the imprint of biogeographic history in the phylogeny.
      Phylogenetic estimation from restriction-site-associated DNA sequencing data for
      156 individuals representing 81 species supports two successive intercontinental
      disjunctions of white oaks: an early vicariance between the Eurasian and American
      white oaks, and a second, independent radiation represented by two relictual
      species. A suite of subsampled and partitioned analyses, however, supports a more
      recent divergence of the Eurasian white oaks from within the American white oaks
      and suggests that historic introgression between the Eurasian white oaks and a
      now-relictual lineage biases concatenated phylogenetic estimates. We demonstrate
      how divergence and reticulation both influence our understanding of the timing
      and nature of diversification and global colonization in these ecologically and
      economically important taxa.

PMID- 28515205
TI  - Family network size and survival across the lifespan of female macaques.
AB  - Two decades of research suggest social relationships have a common evolutionary
      basis in humans and other gregarious mammals. Critical to the support of this
      idea is growing evidence that mortality is influenced by social integration, but
      when these effects emerge and how long they last is mostly unknown. Here, we
      report in adult female macaques that the impact of number of close adult female
      relatives, a proxy for social integration, on survival is not experienced
      uniformly across the life course; prime-aged females with a greater number of
      relatives had better survival outcomes compared with prime-aged females with
      fewer relatives, whereas no such effect was found in older females. Group size
      and dominance rank did not influence this result. Older females were less
      frequent targets of aggression, suggesting enhanced experience navigating the
      social landscape may obviate the need for social relationships in old age. Only
      one study of humans has found age-based dependency in the association between
      social integration and survival. Using the largest dataset for any non-human
      animal to date, our study extends support for the idea that sociality promotes
      survival and suggests strategies employed across the life course change along
      with experience of the social world.

PMID- 28515206
TI  - Widespread ecomorphological convergence in multiple fish families spanning the
      marine-freshwater interface.
AB  - The theoretical definition and quantification of convergence is an increasingly
      topical focus in evolutionary research, with particular growing interest on study
      scales spanning deep phylogenetic divergences and broad geographical areas. While
      much progress has recently been made in understanding the role of convergence in
      driving terrestrial (e.g. anole lizards) and aquatic (e.g. cichlids) radiations,
      little is known about its macroevolutionary effects across environmental
      gradients. This study uses a suite of recently developed comparative approaches
      integrating diverse aspects of morphology, dietary data, habitat affiliation and
      phylogeny to assess convergence across several well-known tropical-temperate fish
      families in the percomorph suborder Terapontoidei, a clade with considerable
      phenotypic and ecological diversity radiating in both marine and freshwater
      environments. We demonstrate significant widespread convergence across many
      lineages occupying equivalent trophic niches, particularly feeding habits such as
      herbivory and biting of attached prey off hard substrates. These include several
      examples of convergent morphotypes evolving independently in marine and
      freshwater clades, separated by deep evolutionary divergences (tens of millions
      of years). The Terapontoidei present a new example of the macroevolutionary
      dynamics of morphological and ecological coevolution in relation to habitat and
      trophic preferences, at a greater phylogenetic and habitat scale than most well
      studied adaptive radiations.

PMID- 28515208
TI  - Glucocorticoid-responsive lymphocytic parathyroiditis and hypocalciuric
      hypercalcemia due to autoantibodies against the calcium-sensing receptor: a case
      report and literature review.
AB  - OBJECTIVE: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric
      hypercalcemia associated with autoantibodies against the calcium-sensing receptor
      (anti-CaSR) are rare and poorly understood conditions. Here, we describe a
      patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with
      associated hypocalciuria, found to have true lymphocytic parathyroiditis on
      histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND
      METHODS: A 64-year-old woman was referred to our clinic for persistent
      hypercalcemia after a subtotal parathyroidectomy. She was normocalcemic until the
      age of 63 years when she was diagnosed with primary hyperparathyroidism. She
      underwent subtotal parathyroidectomy with appropriate intraoperative PTH decline.
      Two weeks post-parathyroidectomy, she presented with persistent hypercalcemia and
      hyperparathyroidism. Urine studies revealed an inappropriately low 24-h urine
      calcium (Ca)/creatinine clearance ratio. Surgical pathology was consistent with
      true lymphocytic parathyroiditis with lymphoid follicles. The presence of
      circulating anti-CaSR antibodies was detected by immunoprecipitation of CaSR by
      the patient's serum. After a 4-week course of prednisone, serum Ca and PTH
      normalized, and her anti-CaSR titers declined. She remains normocalcemic 10
      months after the discontinuation of glucocorticoid therapy. We present this
      patient in the context of the relevant published literature on lymphocytic
      parathyroiditis and acquired hypocalciuric hypercalcemia related to anti-CaSR
      antibodies. CONCLUSIONS: Autoimmune lymphocytic parathyroiditis and acquired
      hypocalciuric hypercalcemia associated with anti-CaSR antibodies is a very rare
      yet important condition to be considered in a patient with acquired PTH-dependent
      hypercalcemia with inappropriate hypocalciuria. Although subtotal
      parathyroidectomy is unlikely to correct the hypercalcemia, this entity may
      respond to a short course of prednisone therapy.

PMID- 28515207
TI  - Early social learning triggers neurogenomic expression changes in a swordtail
      fish.
AB  - Mate choice can play a pivotal role in the nature and extent of reproductive
      isolation between species. Mating preferences are often dependent on an
      individual's social experience with adult phenotypes throughout development. We
      show that olfactory preference in a swordtail fish (Xiphophorus malinche) is
      affected by previous experience with adult olfactory signals. We compare
      transcriptome-wide gene expression levels of pooled sensory and brain tissues
      between three treatment groups that differ by social experience: females with no
      adult exposure, females exposed to conspecifics and females exposed to
      heterospecifics. We identify potential functionally relevant genes and biological
      pathways differentially expressed not only between control and exposure groups,
      but also between groups exposed to conspecifics and heterospecifics. Based on our
      results, we speculate that vomeronasal receptor type 2 paralogs may detect
      species-specific pheromone components and thus play an important role in
      reproductive isolation between species.

PMID- 28515209
TI  - For a healthier future: a virtuous cycle for reducing exposure to persistent
      organic pollutants.
AB  - In the modern society, people are exposed to various pollutants during their
      lifetime. Worldwide, the status of children's health has changed in recent
      decades. Some studies have attempted to identify the causes of these changes and
      whether they relate to pollutant exposure; however, such attempts have faced
      major challenges because human life is complex, involving many social and
      environmental factors. Several long-term cohort studies are being conducted to
      determine the relationship between diseases and social and environmental factors
      in children. Even before we establish complete proof of adverse effects, we
      should attempt to decrease risk to future generations by adopting precautionary
      principles. Environmental exposure to persistent organic pollutants can be
      reduced throughout the stages of life-the fetal period, newborn and infant
      periods, childhood, adolescence and adulthood (preconception) by individuals as
      well as by society as a whole. Through reducing environmental exposure to
      pollutants, adverse health effects can also be reduced, which will contribute to
      healthier future generations. Here, we suggest a virtuous cycle for improving the
      health of future generations through reduced exposure to persistent pollutants.

PMID- 28515211
TI  - Functional Equivalence of the SOX2 and SOX3 Transcription Factors in the
      Developing Mouse Brain and Testes.
AB  - Gene duplication provides spare genetic material that evolution can craft into
      new functions. Sox2 and Sox3 are evolutionarily related genes with overlapping
      and unique sites of expression during embryogenesis. It is currently unclear
      whether SOX2 and SOX3 have identical or different functions. Here, we use
      CRISPR/Cas9-assisted mutagenesis to perform a gene-swap, replacing the Sox3 ORF
      with the Sox2 ORF to investigate their functional equivalence in the brain and
      testes. We show that increased expression of SOX2 can functionally replace SOX3
      in the development of the infundibular recess/ventral diencephalon, and largely
      rescues pituitary gland defects that occur in Sox3 null mice. We also show that
      ectopic expression of SOX2 in the testes functionally rescues the spermatogenic
      defect of Sox3 null mice, and restores gene expression to near normal levels.
      Together, these in vivo data provide strong evidence that SOX2 and SOX3 proteins
      are functionally equivalent.

PMID- 28515210
TI  - Impact of perceived control on all-cause and cardiovascular disease mortality in
      three urban populations of Central and Eastern Europe: the HAPIEE study.
AB  - BACKGROUND: Inverse associations between perceived control and cardiovascular
      disease (CVD) have been reported in studies from Western Europe and the USA. To
      assess this relationship across different populations, we investigated the
      association between perceived control and all-cause and CVD mortality in three
      population-based cohorts of Eastern European countries. METHODS: We analysed data
      from a prospective cohort study in random population samples in Krakow (Poland),
      Novosibirsk (Russia) and six Czech towns. Baseline survey included structured
      questionnaire and objective examination in a clinic. Perceived control was
      assessed using an 11-item scale developed by the MacArthur Foundation Programme
      on Successful Midlife. Information on vital status was obtained from death
      registers. Effect of perceived control on mortality was assessed using Cox
      proportional hazards models. RESULTS: A total of 2377 deaths (1003 from CVD)
      occurred among 27 249 participants over a median 7-year follow-up. In the Czech
      and Polish cohorts, perceived control was inversely associated with mortality;
      the adjusted HRs for the lowest versus highest control quintiles were 1.71 (1.34
      to 2.19) in men and 1.63 (1.14 to 2.35) in women for all-cause mortality and 2.31
      (1.48 to 3.59) and 5.50 (2.14 to 14.13) for CVD deaths. There was no association
      between perceived control and mortality in Russia; the adjusted HRs for all-cause
      mortality were 1.03 (0.79 to 1.34) in men and 1.29 (0.82 to 2.02) in women.
      CONCLUSIONS: Low perceived control was associated with increased risk of all
      cause and CVD mortality in Czech and Polish cohorts but not in Russia. It is
      possible that this inconsistency may partly reflect a different sociocultural
      understanding of the concept of control in Russia.

PMID- 28515212
TI  - Regulation of WNT Signaling at the Neuromuscular Junction by the Immunoglobulin
      Superfamily Protein RIG-3 in Caenorhabditis elegans.
AB  - Perturbations in synaptic function could affect the normal behavior of an animal,
      making it important to understand the regulatory mechanisms of synaptic
      signaling. Previous work has shown that in Caenorhabditis elegans an
      immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to
      maintain normal acetylcholine receptor levels at the neuromuscular junction
      (NMJ). In this study, we elucidate the molecular and functional mechanism of RIG
      3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation)
      assays that presynaptic RIG-3 functions by directly interacting with the
      immunoglobulin domain of the nonconventional Wnt receptor, ROR receptor tyrosine
      kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles. This
      interaction in turn inhibits Wnt/LIN-44 signaling through the ROR/CAM-1 receptor,
      and allows for maintenance of normal acetylcholine receptor, AChR/ACR-16, levels
      at the neuromuscular synapse. Further, this work reveals that RIG-3 and ROR/CAM-1
      function through the beta-catenin/HMP-2 at the NMJ. Taken together, our results
      demonstrate that RIG-3 functions as an inhibitory molecule of the Wnt/LIN-44
      signaling pathway through the RTK, CAM-1.

PMID- 28515213
TI  - Rapid Identification of Five Classes of Carbapenem Resistance Genes Directly from
      Rectal Swabs by Use of the Xpert Carba-R Assay.
AB  - Carbapenemase-producing organisms (CPO) have been identified by global health
      leaders as an urgent threat. Detection of patients with gastrointestinal carriage
      of CPO is necessary to interrupt their spread within health care facilities. In
      this multisite study, we assessed the performance of the Xpert Carba-R test, a
      rapid real-time quantitative PCR (qPCR) assay that detects five families of
      carbapenemase genes (blaIMP, blaKPC, blaNDM, blaOXA-48, and blaVIM) directly from
      rectal swab specimens. Using dual swabs, specimens from 755 patients were
      collected and tested prospectively. An additional 432 contrived specimens were
      prepared by seeding well-characterized carbapenem-susceptible and -nonsusceptible
      strains into a rectal swab matrix and inoculating them onto swabs prior to
      testing. Antimicrobial susceptibility testing, broth enriched culture, and DNA
      sequencing were performed by a central laboratory blind to the Xpert Carba-R
      results. The Xpert Carba-R assay demonstrated a positive percentage of agreement
      (PPA) between 60 and 100% for four targets (blaKPC, blaNDM, blaVIM, and blaOXA
      48) and a negative percentage of agreement (NPA) ranging between 98.9 and 99.9%
      relative to the reference method (culture and sequencing of any carbapenem
      nonsusceptible isolate). There were no prospective blaIMP-positive samples.
      Contrived specimens demonstrated a PPA between 95 and 100% and an NPA of 100% for
      all targets. Testing of rectal swabs directly using the Xpert Carba-R assay is
      effective for rapid detection and identification of CPO from hospitalized
      patients.

PMID- 28515214
TI  - Assessment of a New Lower-Cost Real-Time PCR Assay for Detection of High-Risk
      Human Papillomavirus: Useful for Cervical Screening in Limited-Resource Settings?
AB  - Inexpensive and easy-to-perform human papillomavirus (HPV) tests are needed for
      primary cervical cancer screening in lower-resource regions. In a convenience
      sample of 516 residual exfoliative cervical specimens from the Kaiser Permanente
      Northern California and U.S. National Cancer Institute Persistence and
      Progression Study, we assessed the agreement and clinical performance of a
      simple, inexpensive real-time PCR assay for the detection of 13 carcinogenic HPV
      types (the H13 assay; Hybribio, Hong Kong) that is marketed in limited-resource
      settings compared to previous testing by the Hybrid Capture 2 assay (HC2; Qiagen,
      Germantown, MD) and the Onclarity assay (BD Diagnostics, Sparks, MD). The test
      set was chosen to include many HPV-positive specimens. The reference standard was
      a combination of HC2 and Onclarity results for HPV detection and histologic
      diagnosis of controls (less than cervical intraepithelial neoplasia grade 2
      [<CIN2]) or cases (cervical intraepithelial neoplasia grade 2 or higher [CIN2+])
      for disease status. In this enriched convenience sample, H13 tested positive for
      94.4% of the 108 HC2- and Onclarity-positive CIN2+ specimens and negative for
      88.2% of the 51 HC2- and Onclarity-negative <CIN2 specimens. H13 positivity was
      significantly lower than that of HC2 among women with CIN2+ (89.9% versus 98.7%,
      respectively) (P < 0.001) and <CIN2 (53.5% versus 72.4%, respectively) (P <
      0.001). In conclusion, H13 corresponds well to the combination of HC2 and
      Onclarity and has good clinical accuracy compared to histologic diagnosis, with
      less cross-reactivity with untargeted HPV types than HC2. H13 is a lower-cost HPV
      DNA test that might be useful for primary screening in limited-resource settings.

PMID- 28515215
TI  - Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with
      Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in
      Unrelated Health Care Centers.
AB  - In the Netherlands, the number of cases of infection with New Delhi metallo-beta
      lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak
      of NDM-1-producing Klebsiella pneumoniae infection in a Dutch hospital with
      interspecies transfer of the resistance plasmid and unexpected occurrence in
      other unrelated health care centers (HCCs). Next-generation sequencing was
      performed on 250 carbapenemase-producing Enterobacteriaceae isolates, including
      42 NDM-positive isolates obtained from 29 persons at the outbreak site. Most
      outbreak isolates were K. pneumoniae (n = 26) and Escherichia coli (n = 11), but
      5 isolates comprising three other Enterobacteriaceae species were also cultured.
      The 26 K. pneumoniae isolates had sequence type 873 (ST873), as did 7 unrelated
      K. pneumoniae isolates originating from five geographically dispersed HCCs. The
      33 ST873 isolates that clustered closely together using whole-genome multilocus
      sequence typing (wgMLST) carried the same plasmids and had limited differences in
      the resistome. The 11 E. coli outbreak isolates showed great variety in STs, did
      not cluster using wgMLST, and showed considerable diversity in resistome and
      plasmid profiles. The blaNDM-1 gene-carrying plasmid present in the ST873 K.
      pneumoniae isolates was found in all the other Enterobacteriaceae species
      cultured at the outbreak location and in a single E. coli isolate from another
      HCC. We describe a hospital outbreak with an NDM-1-producing K. pneumoniae strain
      from an unknown source that was also found in patients from five other Dutch HCCs
      in the same time frame without an epidemiological link. Interspecies transfer of
      the resistance plasmid was observed in other Enterobacteriaceae species isolated
      at the outbreak location and in another HCC.

PMID- 28515217
TI  - Analytical and Clinical Evaluation of the PathoNostics AsperGenius Assay for
      Detection of Invasive Aspergillosis and Resistance to Azole Antifungal Drugs
      Directly from Plasma Samples.
AB  - With the proposal to include Aspergillus PCR in the revised European Organization
      for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group
      and National Institute of Allergy and Infectious Diseases Mycoses Study Group
      (EORTC/MSG) definitions for fungal disease, commercially manufactured assays may
      be required to provide standardization and accessibility. The PathoNostics
      AsperGenius assay represents one such test that has the ability to detect a range
      of Aspergillus species as well as azole resistance in Aspergillus fumigatus Its
      performance has been validated on bronchoalveolar lavage (BAL) fluid and serum
      specimens, but recent evidence suggests that testing of plasma may have enhanced
      sensitivity over that with serum. We decided to evaluate the analytical and
      clinical performances of the PathoNostics AsperGenius assay for testing of
      plasma. For the analytical evaluations, plasma was spiked with various
      concentrations of Aspergillus genomic DNA before extraction following
      international recommendations, using two automated platforms. For the clinical
      study, 211 samples from 10 proven/probable invasive aspergillosis (IA) and 2
      possible IA cases and 27 controls were tested. The limits of detection for
      testing of DNA extracted using the bioMerieux EasyMag and Qiagen EZ1 extractors
      were 5 and 10 genomes/0.5-ml sample, respectively. In the clinical study, true
      positivity was significantly greater than false positivity (P < 0.0001). The
      sensitivity and specificity obtained using a single positive result as
      significant were 80% and 77.8%, respectively. If multiple samples were required
      to be positive, specificity was increased to 100%, albeit sensitivity was reduced
      to 50%. The AsperGenius assay provided good clinical performance, but the
      predicted improvement of testing with plasma was not seen, possibly as a result
      of target degradation attributed to sample storage. Prospective testing is
      required to determine the clinical utility of this assay, particularly for the
      diagnosis of azole-resistant disease.

PMID- 28515216
TI  - Assessment of the Cavidi ExaVir Load Assay for Monitoring Plasma Viral Load in
      HIV-2-Infected Patients.
AB  - HIV plasma viral load is an established marker of disease progression and of
      response to antiretroviral therapy, but currently there is no commercial assay
      validated for the quantification of viral load in HIV-2-infected individuals. We
      sought to make the first clinical evaluation of Cavidi ExaVir Load (version 3) in
      HIV-2-infected patients. Samples were collected from a total of 102 individuals
      living in Cape Verde, and the HIV-2 viral load was quantified by both ExaVir Load
      and a reference in-house real-time quantitative PCR (qPCR) used in Portugal in 91
      samples. The associations between viral load and clinical prognostic variables
      (CD4+ T cell counts and antiretroviral therapy status) were similar for
      measurements obtained using ExaVir Load and qPCR. There was no difference between
      the two methods in the capacity to discriminate between nonquantifiable and
      quantifiable HIV-2 in the plasma. In samples with an HIV-2 viral load
      quantifiable by both methods (n = 27), the measurements were highly correlated
      (Pearson r = 0.908), but the ExaVir Load values were systematically higher
      relative to those determined by qPCR (median difference, 0.942 log10 copies/ml).
      A regression model was derived that enables the conversion of ExaVir Load results
      to those that would have been obtained by the reference qPCR. In conclusion,
      ExaVir Load version 3 is a reliable commercial assay to measure viral load in HIV
      2-infected patients and therefore a valuable alternative to the in-house assays
      in current use.

PMID- 28515218
TI  - Group B Streptococcus among Pregnant Women and Newborns in Mirzapur, Bangladesh:
      Colonization, Vertical Transmission, and Serotype Distribution.
AB  - Group B streptococcus (GBS) infection is a leading cause of death among newborns
      in developed countries. Data on the burden of GBS in Asian countries are lacking.
      This study aimed to understand (i) the rate of maternal rectovaginal GBS
      carriage, (ii) the rate of vertical transmission of GBS, as determined by
      culturing ear, umbilicus, and nasal swabs, and (iii) the distribution of GBS
      serotypes. This prospective observational study was conducted between September
      2012 and November 2013 at Kumudini Women's Medical College Hospital, a secondary
      level hospital in Mirzapur, Bangladesh. The study enrolled pregnant women who
      visited the outpatient clinic for antenatal care (ANC) and/or delivered a child
      in the inpatient department of Kumudini Women's Medical College Hospital and the
      babies born to those mothers. Among 1,151 enrolled pregnant women, 172 (15% [95%
      confidence interval [CI], 13 to 17%]) carried GBS; among 68 babies born to
      mothers with carriage, 26 (38% [95% CI, 27 to 51%]) had GBS on their body
      surfaces, indicating vertical transmission. Typing of the isolates (n = 172)
      identified all 10 GBS serotypes, most commonly types Ia (40% [69/172 isolates]),
      V (23% [40/172 isolates]), II (14% [24/172 isolates]), and III (12% [20/172
      isolates]). This study shows that Bangladesh has all of the ingredients for
      invasive GBS disease, including colonization of mothers by invasive serotypes and
      vertical transmission to babies.

PMID- 28515219
TI  - A Novel Stool PCR Test for Helicobacter pylori May Predict Clarithromycin
      Resistance and Eradication of Infection at a High Rate.
AB  - Clarithromycin-based regimens are commonly used as a first-line therapy for
      Helicobacter pylori-positive patients; however, resistance to clarithromycin has
      led to treatment failures. The aim of this study was to evaluate the feasibility
      of using stool samples to detect the presence of H. pylori DNA while concurrently
      detecting mutations associated with resistance to clarithromycin. For this
      purpose, total DNA was extracted from 294 raw stool specimens from H. pylori
      positive and -negative patients. TaqMan real-time PCR amplification was used to
      detect the presence of H. pylori as well as to predict the phenotype of the
      organism and the related outcome for patients treated with clarithromycin.
      Clarithromycin resistance was determined upon analysis of the PCR result.
      Patients were also tested by a urea breath test and were subjected to
      esophagogastroduodenoscopy, followed by histology, culture, and a rapid urease
      test, in order to obtain a consensus patient infection status. Of 294 total stool
      samples, 227 were deemed true positive. The sensitivity of H. pylori detection by
      PCR was 93.8%. Of 213 true-positive samples that were sequenced, 36.2% showed
      point mutations associated with clarithromycin resistance (A2142C, A2142G,
      A2143G). The final correlation of the mutant genotypes as determined by
      sequencing with the eradication of infection was 86%. We found that Helicobacter
      pylori DNA can be detected in human stool specimens with high sensitivity and can
      therefore be used to determine the presence of the bacterium without obtaining a
      biopsy sample. Moreover, genotypic resistance to clarithromycin can be predicted
      without obtaining a biopsy sample, facilitating the choice of the right
      therapeutic approach.

PMID- 28515220
TI  - Culture-Based Methods and Molecular Tools for Azole-Resistant Aspergillus
      fumigatus Detection in a Belgian University Hospital.
AB  - Azole-resistant Aspergillus fumigatus is an increasing worldwide problem with
      major clinical implications. Surveillance is warranted to guide clinicians to
      provide optimal treatment to patients. To investigate azole resistance in
      clinical Aspergillus isolates in our institution, a Belgian university hospital,
      we conducted a laboratory-based surveillance between June 2015 and October 2016.
      Two different approaches were used: a prospective culture-based surveillance
      using VIPcheck on unselected A. fumigatus (n = 109 patients, including 19
      patients with proven or probable invasive aspergillosis [IA]), followed by
      molecular detection of mutations conferring azole resistance, and a retrospective
      detection of azole-resistant A. fumigatus in bronchoalveolar lavage fluid using
      the commercially available AsperGenius PCR (n = 100 patients, including 29
      patients with proven or probable IA). By VIPcheck, 25 azole-resistant A.
      fumigatus specimens were isolated from 14 patients (12.8%). Of these 14 patients,
      only 2 had proven or probable IA (10.5%). Mutations at the cyp51A gene were
      observed in 23 of the 25 A. fumigatus isolates; TR34/L98H was the most prevalent
      mutation (46.7%), followed by TR46/Y121F/T289A (26.7%). Twenty-seven (27%)
      patients were positive for the presence of Aspergillus species by AsperGenius
      PCR. A. fumigatus was detected by AsperGenius in 20 patients, and 3 of these
      patients carried cyp51A mutations. Two patients had proven or probable IA and
      cyp51A mutation (11.7%). Our study has shown that the detection of azole
      resistant A. fumigatus in clinical isolates was a frequent finding in our
      institution. Hence, a rapid method for resistance detection may be useful to
      improve patient management. Centers that care for immunocompromised patients
      should perform routine surveillance to determine their local epidemiology.

PMID- 28515223
TI  - Associations between male reproductive characteristics and the outcome of
      assisted reproductive technology (ART).
AB  - The present study was designed to investigate the relationships between
      indicators of male body mass index (BMI), age, reproductive hormone levels, semen
      parameters, and the outcomes of assisted reproductive technology (ART). The
      clinical data were collected from 636 couples who underwent ART between January,
      2013 and December, 2015 at the reproductive center involved in our study.
      Pearson's correlation or Spearman rank correlation was applied to establish the
      relevant correlation coefficients. The correlation between influence factors' and
      pregnancy outcomes was analyzed using the Logistic regression model. Analyses
      were conducted using SPSS software. Male BMI was found to be negatively
      correlated with testosterone (T) (P<0.05), while follicle-stimulating hormone
      (FSH) was negatively correlated with semen parameters (P<0.05). Luteinizing
      hormone (LH) was found to be negatively correlated with total sperm count, normal
      sperm morphology, and abortion (all P<0.05). Clinical pregnancy was related to
      sperm concentration and female age (P<0.05), and live birth was found to be
      associated only with female age (P<0.05). Male BMI was associated with the
      secretion of reproductive hormones, but had no effect on sperm parameters or ART
      outcome. A higher male age was also negatively connected with the outcome of
      clinical pregnancy. Reproductive hormones were not associated with ART outcome.
      Sperm concentration and female age were important factors influencing ART
      clinical pregnancy, while the only significant factor influencing live birth was
      female age. Levels of obesity-related inflammatory indicators (i.e. free fatty
      acid (FFA), glutathione peroxidase (GSH-Px), human inhibin-B (IHNB), interleukin
      1 (IL-1), insulin-like growth factor-1 (IGF-1), and reactive oxygen species
      (ROS)) also varied with degrees of BMI. The present study provides information on
      the associations between male reproductive characteristics and the outcome of
      ART, which may contribute to improved strategies to help couples achieve better
      pregnancy outcomes.

PMID- 28515222
TI  - Zebrafish models for functional and toxicological screening of nanoscale drug
      delivery systems: promoting preclinical applications.
AB  - Preclinical screening with animal models is an important initial step in clinical
      translation of new drug delivery systems. However, establishing efficacy,
      biodistribution, and biotoxicity of complex, multicomponent systems in small
      animal models can be expensive and time-consuming. Zebrafish models represent an
      alternative for preclinical studies for nanoscale drug delivery systems. These
      models allow easy optical imaging, large sample size, and organ-specific studies,
      and hence an increasing number of preclinical studies are employing zebrafish
      models. In this review, we introduce various models and discuss recent studies of
      nanoscale drug delivery systems in zebrafish models. Also in the end, we proposed
      a guideline for the preclinical trials to accelerate the progress in this field.

PMID- 28515221
TI  - Regulation of cerebral arterial BKCa channels by angiotensin II signaling in
      adult offspring exposed to prenatal high sucrose diets.
AB  - Prenatal insults have been shown to affect vascular functions, leading to
      increased risks of cardiovascular diseases in offspring. The present study
      determined whether high sucrose (HS) intake in pregnancy affected central
      vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley
      rats were fed a standard food and tap water with normal or high (20%) sucrose
      content during pregnancy. Offspring were maintained with normal diets and tap
      water. Central vascular functions and related ion channels were assessed in male
      offspring at 5 months old. Compared with the control, angiotensin II (AII)
      induced vasoconstrictions were significantly higher in the MCA of the offspring
      exposed to prenatal HS. In the MCA, large conductance Ca2+-activated K+ channels
      (BKCa) currents were decreased with a reduction of opening frequency, sensitivity
      to intracellular Ca2+/membrane voltage, and BKbeta1 expression. mRNA levels of
      AT1alpha and AT2, as well as AT1/AT2 ratio, were significantly increased in the
      MCA of offspring following exposure to prenatal HS diets. The data suggested that
      prenatal HS diets could alter microvascular activities in the MCA, probably via
      changes of BKCa channels in the brain.

PMID- 28515224
TI  - Activin A regulates activation of mouse neutrophils by Smad3 signalling.
AB  - Activin A, a member of the transforming growth factor beta superfamily, acts as a
      pro-inflammatory factor in acute phase response, and influences the pathological
      progress of neutrophil-mediated disease. However, whether activin A can exert an
      effect on the activities of neutrophils remains unclear. In this study, we found
      that the release of activin A was enhanced from neutrophils of mouse when
      stimulated with lipopolysaccharide. Furthermore, neutrophils were not only the
      source of activin A but also the target cells in response to activin A, in which
      canonical activin signalling components existed, and levels of ACTRIIA, SMAD3 and
      p-SMAD3 proteins were elevated in activin A-treated neutrophils. Next, the role
      of activin A was determined in regulation of neutrophils activities. Our data
      revealed that activin A induced O2- release and reactive oxygen species
      production, promoted IL-6 release, and enhanced phagocytosis, but failed to
      attract neutrophils migrating across the trans-well membrane. Moreover, we found
      that effect of activin A on IL-6 release from the peritoneal neutrophils of mouse
      was significantly attenuated by in vivo Smad3 knockdown. In summary, these data
      demonstrate that activin A can exert an effect on neutrophils activation in an
      autocrine/paracrine manner through Smad3 signalling, suggesting that activin A is
      an important regulator of neutrophils.

PMID- 28515226
TI  - A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without
      inducing neutropenia in nonhuman primates.
AB  - Neutrophils are the most abundant WBCs and have an essential role in the
      clearance of pathogens. Tight regulation of neutrophil numbers and their
      recruitment to sites of inflammation is critical in maintaining a balanced immune
      response. In various inflammatory conditions, such as rheumatoid arthritis,
      vasculitis, cystic fibrosis, and inflammatory bowel disease, increased serum G
      CSF correlates with neutrophilia and enhanced neutrophil infiltration into
      inflamed tissues. We describe a fully human therapeutic anti-G-CSFR antibody
      (CSL324) that is safe and well tolerated when administered via i.v. infusion to
      cynomolgus macaques. CSL324 was effective in controlling G-CSF-mediated
      neutrophilia when administered either before or after G-CSF. A single ascending
      dose study showed CSL324 did not alter steady-state neutrophil numbers, even at
      doses sufficient to completely prevent G-CSF-mediated neutrophilia. Weekly
      infusions of CSL324 (<=10 mg/kg) for 3 wk completely neutralized G-CSF-mediated
      pSTAT3 phosphorylation without neutropenia. Moreover, repeat dosing up to 100
      mg/kg for 12 wk did not result in neutropenia at any point, including the 12-wk
      follow-up after the last infusion. In addition, CSL324 had no observable effect
      on basic neutrophil functions, such as phagocytosis and oxidative burst. These
      data suggest that targeting G-CSFR may provide a safe and effective means of
      controlling G-CSF-mediated neutrophilia as observed in various inflammatory
      diseases.

PMID- 28515225
TI  - Energy metabolic pathways control the fate and function of myeloid immune cells.
AB  - The past decade has seen a significant interest in investigating the
      intracellular metabolism of cells of the immune system. This has increased the
      realization that immune cells endure metabolic reprogramming upon responding to
      pathogen-derived or inflammatory signals. More importantly, not only does this
      metabolic switch provide for the bioenergetic and biosynthetic demands but also
      it, in a highly specific manner, determines the cellular fate and function. In
      this review, we discuss the metabolic aspects that regulate the differentiation
      and function of myeloid cells, pivotal for both innate and adaptive immunity. The
      manipulation of these pathways can alter the function of these cells and
      therefore, could provide novel therapeutic approaches in cancer and other chronic
      inflammatory conditions.

PMID- 28515227
TI  - Frontline Science: Eosinophil-deficient MBP-1 and EPX double-knockout mice link
      pulmonary remodeling and airway dysfunction with type 2 inflammation.
AB  - Eosinophils and the release of cationic granule proteins have long been
      implicated in the development of the type 2-induced pathologies linked with
      respiratory inflammation. Paradoxically, the ablation of the two genes encoding
      the most abundant of these granule proteins, major basic protein-1 (MBP-1) and
      eosinophil peroxidase (EPX), results in a near collapse of eosinophilopoiesis.
      The specificity of this lineage ablation and the magnitude of the induced
      eosinopenia provide a unique opportunity to clarify the importance of eosinophils
      in acute and chronic inflammatory settings, as well as to identify potential
      mechanism(s) of action linked with pulmonary eosinophils in those settings.
      Specifically, we examined these issues by assessing the induced immune responses
      and pathologies occurring in MBP-1-/-/EPX-/- mice after 1) ovalbumin
      sensitization/provocation in an acute allergen-challenge protocol, and 2)
      crossing MBP-1-/-/EPX-/- mice with a double-transgenic model of chronic type 2
      inflammation (i.e., I5/hE2). Acute allergen challenge and constitutive
      cytokine/chemokine expression each induced the accumulation of pulmonary
      eosinophils in wild-type controls that was abolished in the absence of MBP-1 and
      EPX (i.e., MBP-1-/-/EPX-/- mice). The expression of MBP-1 and EPX was also
      required for induced lung expression of IL-4/IL-13 in each setting and, in turn,
      the induced pulmonary remodeling events and lung dysfunction. In summary, MBP-1-/
      /EPX-/- mice provide yet another definitive example of the immunoregulatory role
      of pulmonary eosinophils. These results highlight the utility of this unique
      strain of eosinophil-deficient mice as part of in vivo model studies
      investigating the roles of eosinophils in health and disease settings.

PMID- 28515229
TI  - Unique cell biological profiles of retinal disease-causing missense mutations in
      the polarity protein Crumbs.
AB  - Mutations in human crumbs 1 (CRB1) are a major cause of retinal diseases that
      lead to blindness. CRB1 is a transmembrane protein found in the inner segment of
      photoreceptor cells (PRCs) and the apical membrane of Muller glia. The function
      of the extracellular region of CRB1 is poorly understood, although more than 80
      disease-causing missense mutations have been mapped to it. We have recreated four
      of these mutations, affecting different extracellular domains, in Drosophila
      Crumbs (Crb). Crb regulates epithelial polarity and growth, and contributes to
      PRC differentiation and survival. The mutant Crb isoforms showed a remarkable
      diversity in protein abundance, subcellular distribution and ability to rescue
      the lack of endogenous Crb, elicit a gain-of-function phenotype or promote PRC
      degeneration. Interestingly, although expression of mutant isoforms led to a
      substantial rescue of the developmental defects seen in crb mutants, they
      accelerated PRC degeneration compared to that seen in retinas that lacked Crb,
      indicating that the function of Crb in cellular differentiation and cell survival
      depends on distinct molecular pathways. Several Crb mutant proteins accumulated
      abnormally in the rhabdomere and affected rhodopsin trafficking, suggesting that
      abnormal rhodopsin physiology contributes to Crb/CRB1-associated retinal
      degeneration.

PMID- 28515228
TI  - NK1.1+ cells promote sustained tissue injury and inflammation after trauma with
      hemorrhagic shock.
AB  - Various cell populations expressing NK1.1 contribute to innate host defense and
      systemic inflammatory responses, but their role in hemorrhagic shock and trauma
      remains uncertain. NK1.1+ cells were depleted by i.p. administration of anti
      NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock
      with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL
      6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were
      measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h.
      The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well
      as intracellular staining for TNF-alpha, IFN-gamma, and MCP-1 in liver cell
      populations were determined by flow cytometry. Control mice subjected to HS/T
      exhibited end organ damage manifested by marked increases in circulating ALT,
      AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut
      injury. Although NK1.1+ cell-depleted mice exhibited a similar degree of organ
      damage as nondepleted animals at 6 h, NK1.1+ cell depletion resulted in marked
      suppression of both liver and gut injury by 24 h after HS/T. These findings
      indicate that NK1.1+ cells contribute to the persistence of inflammation leading
      to end organ damage in the liver and gut.

PMID- 28515230
TI  - Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive
      neurons and is maintained during aging.
AB  - Maturation of nociceptive neurons depends on changes in transcription factors,
      ion channels and neuropeptides. Mature nociceptors initiate pain in part by
      drastically reducing the activation threshold via intracellular sensitization
      signaling. Whether sensitization signaling also changes during development and
      aging remains so far unknown. Using a novel automated microscopy approach, we
      quantified changes in intracellular signaling protein expression and in their
      signaling dynamics, as well as changes in intracellular signaling cascade wiring,
      in sensory neurons from newborn to senescent (24 months of age) rats. We found
      that nociceptive subgroups defined by the signaling components protein kinase A
      (PKA)-RIIbeta (also known as PRKAR2B) and CaMKIIalpha (also known as CAMK2A)
      developed at around postnatal day 10, the time of nociceptor maturation. The
      integrative nociceptor marker, PKA-RIIbeta, allowed subgroup segregation earlier
      than could be achieved by assessing the classical markers TRPV1 and Nav1.8 (also
      known as SCN10A). Signaling kinetics remained constant over lifetime despite in
      part strong changes in the expression levels. Strikingly, we found a mechanism
      important for neuronal memory - i.e. the crosstalk from cAMP and PKA to ERK1 and
      ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) - to emerge
      postnatally. Thus, maturation of nociceptors is closely accompanied by altered
      expression, activation and connectivity of signaling pathways known to be central
      for pain sensitization and neuronal memory formation.

PMID- 28515231
TI  - A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3
      and adhesion plasticity.
AB  - A change regarding the extent of adhesion - hereafter referred to as adhesion
      plasticity - between adhesive and less-adhesive states of mammalian cells is
      important for their behavior. To investigate adhesion plasticity, we have
      selected a stable isogenic subpopulation of human MDA-MB-468 breast carcinoma
      cells growing in suspension. These suspension cells are unable to re-adhere to
      various matrices or to contract three-dimensional collagen lattices. By using
      transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3)
      as a determinant of adhesion plasticity. Tns3 is strongly reduced at mRNA and
      protein levels in suspension cells. Furthermore, by transiently challenging
      breast cancer cells to grow under non-adherent conditions markedly reduces Tns3
      protein expression, which is regained upon re-adhesion. Stable knockdown of Tns3
      in parental MDA-MB-468 cells results in defective adhesion, spreading and
      migration. Tns3-knockdown cells display impaired structure and dynamics of focal
      adhesion complexes as determined by immunostaining. Restoration of Tns3 protein
      expression in suspension cells partially rescues adhesion and focal contact
      composition. Our work identifies Tns3 as a crucial focal adhesion component
      regulated by, and functionally contributing to, the switch between adhesive and
      non-adhesive states in MDA-MB-468 cancer cells.

PMID- 28515232
TI  - The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus
      transport.
AB  - Transport of large cargo through the cytoplasm requires motor proteins and
      polarized filaments. Viruses that replicate in the nucleus of post-mitotic cells
      use microtubules and the dynein-dynactin motor to traffic to the nuclear membrane
      and deliver their genome through nuclear pore complexes (NPCs) into the nucleus.
      How virus particles (virions) or cellular cargo are transferred from microtubules
      to the NPC is unknown. Here, we analyzed trafficking of incoming cytoplasmic
      adenoviruses by single-particle tracking and super-resolution microscopy. We
      provide evidence for a regulatory role of CRM1 (chromosome-region-maintenance-1;
      also known as XPO1, exportin-1) in juxta-nuclear microtubule-dependent adenovirus
      transport. Leptomycin B (LMB) abolishes nuclear targeting of adenovirus. It binds
      to CRM1, precludes CRM1-cargo binding and blocks signal-dependent nuclear export.
      LMB-inhibited CRM1 did not compete with adenovirus for binding to the nucleoporin
      Nup214 at the NPC. Instead, CRM1 inhibition selectively enhanced virion
      association with microtubules, and boosted virion motions on microtubules less
      than ~2 um from the nuclear membrane. The data show that the nucleus provides
      positional information for incoming virions to detach from microtubules, engage a
      slower microtubule-independent motility to the NPC and enhance infection.

PMID- 28515234
TI  - A methodological approach for assessing the uptake of core outcome sets using
      ClinicalTrials.gov: findings from a review of randomised controlled trials of
      rheumatoid arthritis.
AB  - Objective To assess the uptake of the rheumatoid arthritis core outcome set using
      a new assessment method of calculating uptake from data in clinical trial
      registry entries.Design Review of randomised trials.Setting
      ClinicalTrials.gov.Subjects 273 randomised trials of drug interventions for the
      treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between
      2002 and 2016. Full publications were identified for completed studies from
      information in the trial registry or from an internet search using Google and the
      citation database Web of Science.Main outcome measure The percentage of trials
      reporting or planning to measure the rheumatoid arthritis core outcome set
      calculated from the information presented in the trial registry and compared with
      the percentage reporting the rheumatoid arthritis core outcome set in the
      resulting trial publications.Results The full rheumatoid arthritis core outcome
      set was reported in 81% (116/143) of trials identified on the registry as
      completed (or terminated) for which results were found in either the published
      literature or the registry. For trials identified on the registry as completed
      (or terminated), using information only available in the registry gives an
      estimate for uptake of 77% (145/189).Conclusions The uptake of the rheumatoid
      arthritis core outcome set in clinical trials has continued to increase over
      time. Using the information on outcomes listed for completed or terminated
      studies in a trial registry provides a reasonable estimate of the uptake of a
      core outcome set and is a more efficient and up-to-date approach than examining
      the outcomes in published trial reports. The method proposed may provide an
      efficient approach for an up-to-date assessment of the uptake of the 300 core
      outcome sets already published.

PMID- 28515233
TI  - A Wntless-SEC12 complex on the ER membrane regulates early Wnt secretory vesicle
      assembly and mature ligand export.
AB  - Wntless (Wls) transports Wnt molecules for secretion; however, the cellular
      mechanism underlying the initial assembly of Wnt secretory vesicles is still not
      fully defined. Here, we performed proteomic and mutagenic analyses of mammalian
      Wls, and report a mechanism for formation of early Wnt secretory vesicles on ER
      membrane. Wls forms a complex with SEC12 (also known as PREB), an ER membrane
      localized guanine nucleotide-exchange factor (GEF) activator of the SAR1 (the
      SAR1A isoform) small GTPase. Compared to palmitoylation-deficient Wnt molecules,
      binding of mature Wnt to Wls increases Wls-SEC12 interaction and promotes
      association of Wls with SAR1, the key activator of the COPII machinery.
      Incorporation of Wls into this exporting ER compartment is affected by Wnt ligand
      binding and SEC12 binding to Wls, as well as the structural integrity and,
      potentially, the folding of the cytosolic tail of Wls. In contrast, Wls-SEC12
      binding is stable, with the interacting interface biochemically mapped to
      cytosolic segments of individual proteins. Mutant Wls that fails to communicate
      with the COPII machinery cannot effectively support Wnt secretion. These data
      suggest that formation of early Wnt secretory vesicles is carefully regulated to
      ensure proper export of functional ligands.

PMID- 28515236
TI  - Resonance frequencies of honeybee (Apis mellifera) wings.
AB  - During flight, insect wings bend and twist under the influence of aerodynamic and
      inertial forces. We tested whether wing resonance of honeybees (Apis mellifera)
      matches the wingbeat frequency, against the 'stiff element' hypothesis that the
      wing's first longitudinal mode exceeds the wingbeat frequency. Six bees were
      immobilized with their right wing pair outspread, and stimulated with a shaker
      while the normal modes were recorded with a scanning Doppler laser vibrometer.
      The lowest normal mode of the wings was the first longitudinal bending mode and,
      at 602+/-145 Hz, was greater than the wingbeat frequency of 234+/-13.9 Hz. Higher
      order normal modes of the wing tended to incorporate nodal lines in the chordwise
      direction of the trailing edge, suggesting that their mode shape did not strongly
      resemble wing deformation during flapping flight. These results support the stiff
      element hypothesis for Apis mellifera.

PMID- 28515235
TI  - Insulin-like growth factor signaling regulates developmental trajectory
      associated with diapause in embryos of the annual killifish Austrofundulus
      limnaeus.
AB  - Annual killifishes exhibit a number of unique life history characters including
      the occurrence of embryonic diapause, unique cell movements associated with
      dispersion and subsequent reaggregation of the embryonic blastomeres, and a short
      post-embryonic life span. Insulin-like growth factor (IGF) signaling is known to
      play a role in the regulation of metabolic dormancy in a number of animals but
      has not been explored in annual killifishes. The abundance of IGF proteins during
      development and the developmental effects of blocking IGF signaling by
      pharmacological inhibition of the insulin-like growth factor I receptor (IGF1R)
      were explored in embryos of the annual killifish Austrofundulus limnaeus Blocking
      of IGF signaling in embryos that would normally escape entrance into diapause
      resulted in a phenotype that was remarkably similar to that of embryos entering
      diapause. IGF-I protein abundance spikes during early development in embryos that
      will not enter diapause. In contrast, IGF-I levels remain low during early
      development in embryos that will enter diapause II. IGF-II protein is packaged at
      higher levels in escape-bound embryos compared with diapause-bound embryos.
      However, IGF-II levels quickly decrease and remain low during early development
      and only increase substantially during late development in both developmental
      trajectories. Developmental patterns of IGF-I and IGF-II protein abundance under
      conditions that would either induce or bypass entrance into diapause are
      consistent with a role for IGF signaling in the regulation of developmental
      trajectory and entrance into diapause in this species. We propose that IGF
      signaling may be a unifying regulatory pathway that explains the larger suite of
      characters that are associated with the complex life history of annual
      killifishes.

PMID- 28515237
TI  - Increasing the illumination slowly over several weeks protects against light
      damage in the eyes of the crustacean Mysis relicta.
AB  - The eyes of two glacial-relict populations of opossum shrimp Mysis relicta
      inhabiting the different photic environments of a deep, dark-brown freshwater
      lake and a variably lit bay of the Baltic Sea differ in their susceptibility to
      functional depression from strong light exposures. The lake population is much
      more vulnerable than the sea population. We hypothesized that the difference
      reflects physiological adaptation mechanisms operating on long time scales rather
      than genetically fixed differences between the populations. To test this, we
      studied how acclimation to ultra-slowly increased illumination (on time scales of
      several weeks to months) affected the resilience of the eyes to bright-light
      exposures. Light responses of whole eyes were measured by electroretinography,
      the visual-pigment content of single rhabdoms by microspectrophotometry and the
      structural integrity of photoreceptor cells by electron microscopy (EM). Slow
      acclimation mitigated and even abolished the depression of photoresponsiveness
      caused by strong light exposures, making a dramatic difference especially in the
      lake animals. Still, acclimation in the sea animals was faster and the EM studies
      suggested intrinsic differences in the dynamics of microvillar membrane cycling.
      In conclusion, we report a novel form of physiological adaptation to general
      light levels, effective on the time scale of seasonal changes. It explains part
      but not all of the differences in light tolerance between the lake and sea
      populations.

PMID- 28515239
TI  - The NCCN 22nd Annual Conference: Discussing Treatment Disparities, the Doctor
      Patient Relationship, the Latest NCCN Guidelines Updates, and More.

PMID- 28515238
TI  - Labrid cleaner fishes show kinematic convergence as juveniles despite variation
      in morphology.
AB  - Cleaning, a dietary strategy in which mucus or ectoparasites are removed and
      consumed off other taxa, is performed facultatively or obligately in a variety of
      species. We explored whether species in the Labridae (wrasses, parrotfishes) of
      varying ecological specialization employ similar mechanisms of prey capture. In
      investigating feeding on attached prey among juveniles of 19 species of wrasses,
      we found that patterns of biting in wrasses are influenced by the interaction
      between the maxilla and a feature of the premaxilla which we term the maxillary
      crest. Premaxillary motion during biting appears to be guided by the relative
      size of the crest. In many cases, this results in a 'premaxillary bite' wherein
      the premaxillae rapidly move anteroventrally to meet the lower jaws and deliver a
      protruded bite. Cleaners in the Labrichthyini tribe, however, exhibited reduced
      or absent maxillary crests. This coincided with a distinct kinematic pattern of
      prey capture in these labrichthyine cleaners, coupled with some of the fastest
      and lowest-excursion jaw movements. Although evidence of kinematic specialization
      can be found in these labrichthyines (most notably in the obligate cleaners in
      Labroides), we found that facultative cleaners from other lineages similarly
      evolved reductions in excursions and timing. Convergence in feeding kinematics is
      thus apparent despite varying degrees of cleaning specialization and underlying
      morphological features.

PMID- 28515240
TI  - NCCN Roundtable Tackles Disparities in Cancer Care.
AB  - During a roundtable on disparities in cancer care at the recent NCCN 22nd Annual
      Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care,
      panelists from a variety of disciplines brought professional and personal
      experiences to the discussion of eliminating cancer disparities and reducing
      differences in incidence and mortality rates among minority populations. The
      panel agreed that these issues must be addressed through research in prevention,
      screening, clinical trials, and equal access to quality care.

PMID- 28515241
TI  - Use of Biomarkers and Multigene Assays in Breast Cancer.
AB  - All patients with early breast cancer should be classified by subgroup through
      testing estrogen receptor, progesterone receptor, and HER2 status, with or
      without Ki-67 proliferation percentage. Genomic expression profiling aids
      clinical decision-making in most patients, because most are estrogen receptor
      positive. The commercially available classifiers are prognostic for distant
      recurrence in node-negative and also node-positive patients. Patients at
      genomically low risk have excellent 5-year outcomes with endocrine therapy alone.
      Some assays also predict for benefit from adjuvant endocrine therapy and
      chemotherapy in node-negative and node-positive patients, but with varying levels
      of evidence. Genomic classifiers are also prognostic of late relapse and may
      predict benefit from extended adjuvant endocrine therapy.

PMID- 28515242
TI  - New Approaches to Endocrine Therapy for Breast Cancer.
AB  - The management of advanced hormone receptor-positive disease has evolved with the
      emergence of CDK4/6 inhibitors. Improvements in progression-free survival of
      approximately 10 months were noted in pivotal trials of palbociclib. Strong
      efficacy was also seen with ribociclib, which was recently approved by the FDA.
      In the adjuvant treatment setting of hormone receptor-positive disease, an
      important issue for consideration is the duration of endocrine therapy.

PMID- 28515243
TI  - NCCN Guidelines Update: Evolving Radiation Therapy Recommendations for Breast
      Cancer.
AB  - In the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast
      Cancer, among adjuvant radiotherapy options for whole-breast irradiation after
      breast-conserving surgery, hypofractionation is preferred. For the use of
      accelerated partial-breast irradiation, the NCCN Guidelines have adopted the
      updated definition of "suitability" used by the American Society for Radiation
      Oncology. Regional nodal irradiation is indicated-either in the setting of breast
      conserving surgery or after mastectomy-for women with >=4 positive nodes and
      should be strongly considered for 1 to 3 positive lymph nodes and select patients
      with node-negative disease deemed at high risk for recurrence.

PMID- 28515244
TI  - What, When, and How of Biomarker Testing in Non-Small Cell Lung Cancer.
AB  - Biomarker testing is recommended for all patients diagnosed with non-small cell
      lung cancer. At a minimum, testing should include the mutations/fusions EGFR,
      ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA
      approved therapies are available for these alterations. Other actionable
      molecular findings include RET rearrangements, BRAFV600E mutations, and MET exon
      14 alterations. If adequate testing was not performed at treatment initiation,
      molecular testing should be performed before administration of subsequent lines
      of therapy. In patients with EGFR-mutant lung cancer, when resistance develops,
      physicians should seek to identify the T790M mutation using plasma and tissue
      assays, because osimertinib therapy is available for this mutation.

PMID- 28515245
TI  - Biomarker-Based Treatment Selection in Non-Small Cell Lung Cancer.
AB  - Patients with non-small cell lung cancer must be tested for biomarkers.
      Currently, treatments directed against EGFR, ALK, and ROS1 mutations are standard
      of care. A number of emerging new targets and treatments are on the horizon.

PMID- 28515246
TI  - Immunotherapies for Lung Cancer.
AB  - In 2017, immunotherapy is the standard of care for patients with non-small cell
      lung cancer (NSCLC) either in the first or second line depending on programmed
      death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab
      is currently the standard of care for patients whose tumors express PD-L1 >50%.
      All patients with NSCLC should undergo PD-L1 testing before initiating treatment
      on pembrolizumab. For patients not eligible in the first line, immunotherapy is
      the standard of care for most in the second line. Nivolumab and atezolizumab are
      approved in all patients as second-line therapies after platinum-based doublet
      failure regardless PD-L1 expression level, although pembrolizumab is approved as
      second-line therapy for those whose tumors express PD-L1 >1%.

PMID- 28515247
TI  - Keynote Address: When Breath Becomes Air-As Physician Becomes Patient.
AB  - As part of the NCCN 22nd Annual Conference: Improving the Quality, Effectiveness,
      and Efficiency of Cancer Care, Lucy Kalanithi, MD, wife of now-deceased best
      selling author Paul Kalanithi (When Breath Becomes Air), and Heather Wakelee, MD,
      Paul's oncologist, discussed-for the first time together in a public forum-Paul's
      experience of going from a neurosurgery resident to a patient with cancer with a
      terminal diagnosis. Robert Carlson, MD, moderated the discussion.

PMID- 28515248
TI  - Systemic Management of Colorectal Cancer.
AB  - Advances have been made in the systemic treatment of colorectal cancer, with
      approximately 12 chemotherapy or biologic agents approved for use as a single
      agent or in a combination. However, numerous gaps in our understanding of the
      disease remain, such as the lack of benefit with biologics in the adjuvant
      setting, the absence of biomarkers for most systemic therapies, and the reason
      why left-sided and right-sided tumors behave differently. At the 22nd NCCN Annual
      Conference, Dr. Wells A. Messersmith presented several impactful updates to the
      2017 NCCN Clinical Practice Guidelines in Oncology for Colon Cancer and reviewed
      the outcomes with a host of therapies used for both early-stage and metastatic
      disease.

PMID- 28515249
TI  - Incorporating New Systemic Therapies in Kidney Cancer Treatment.
AB  - In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for
      advanced renal cell carcinoma. Independent review of frontline cabozantinib
      therapy may alter standard of care for patients at intermediate and poor risk.
      Multiple agents show a survival advantage in the second-line setting, including
      nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of
      subsequent therapy will depend on patient disease status, comorbidities, and
      resource availability.

PMID- 28515250
TI  - Challenges of Toxicity Management in Immuno-Oncology.
AB  - Immunotherapies are conveying unprecedented efficacy in some tumor types, but
      with this success comes challenges in managing toxicities that are distinct from
      those of cytotoxic agents. Although most immune-related adverse events can be
      ameliorated by temporarily withholding the drug and administering steroids, grade
      3 to 4 toxicities can be challenging and some adverse effects can be long
      lasting. NCCN has developed an immunotherapy teaching and monitoring tool that
      can help in evaluating and managing these autoimmune-mediated inflammatory
      conditions, which can affect virtually all organ systems.

PMID- 28515251
TI  - New Treatment Options for the Management of Multiple Myeloma.
AB  - Multiple myeloma (MM) is a complex disease characterized by considerable genetic
      heterogeneity. The updated NCCN Guidelines for MM have added new "preferred"
      regimens for transplant and nontransplant candidates, and have moved some
      formerly "preferred" regimens to the "other" category. Supportive care has
      improved outcomes for patients, and new treatments in combination have extended
      survival for patients with MM. Novel agents on the horizon are poised to raise
      the bar even further.

PMID- 28515252
TI  - Chronic Lymphocytic Leukemia: Individualizing Treatment Approach.
AB  - A host of new therapies are now available for treating patients with chronic
      lymphocytic leukemia (CLL) in both the upfront and relapsed or refractory
      settings. Although the optimal use of these agents is still being defined,
      established and emerging prognostic markers aid in the selection of appropriate
      treatment with the best chance of success. At the NCCN 22nd Annual Conference,
      Dr. Andrew Zelenetz discussed the role of the CLL-International Prognostic Index
      for risk stratification, reviewed optimal first-line therapy options, and then
      presented updated clinical trial data on the novel agents being used in the
      relapsed or refractory setting. The hope is that chronic therapy will be replaced
      by combinations that provide high rates of minimal residual disease negativity
      with durable remissions.

PMID- 28515253
TI  - Strategies for Management of Relapsed or Refractory Hodgkin Lymphoma.
AB  - The advent of effective therapies has improved outcomes for those with newly
      diagnosed Hodgkin lymphoma (HL), with a resulting cure rate of at least 80%.
      However, with limited data on therapeutic options in the setting of advanced
      disease, individualized treatment is recommended, and potential long-term effects
      of therapy remain a key consideration. At the NCCN 22nd Annual Conference, Dr.
      Leo I. Gordon explored strategies for systemic therapy in the relapsed or
      refractory setting, focusing primarily on the standard of high-dose
      therapy/autologous stem cell rescue, the CD30-targeted antibody drug conjugate
      brentuximab vedotin, and checkpoint inhibition.

PMID- 28515254
TI  - NCCN Debuts New Guidelines for Myeloproliferative Neoplasms.
AB  - For the first time, NCCN has published guidelines specifically geared toward
      treating myeloproliferative neoplasms (MPNs). The first set of guidelines was
      developed for myelofibrosis (MF), and was presented at the NCCN 22nd Annual
      Conference. Future guidelines will be issued for polycythemia vera, essential
      thrombocytopenia, and atypical MPNs. Patients with MF can have an unpredictable
      course, one that is largely dependent on the presence of certain molecular
      alterations. Models are currently emerging that take into account molecular
      factors. Only one drug is currently approved for MF, the oral JAK1/2 inhibitor
      ruxolitinib, which has been shown to significantly reduce splenomegaly and
      improve symptoms.

PMID- 28515255
TI  - Active Systemic Treatment of Pancreatic Cancer.
AB  - By 2020, pancreatic cancer is expected to be the second most common cause of
      cancer-related death, exceeded only by lung cancer. During her presentation at
      the NCCN 22nd Annual Conference, Dr. Margaret Tempero offered an update on the
      current state of systemic treatment of pancreatic cancer, focusing on
      resectable/borderline resectable, locally advanced, and metastatic disease.

PMID- 28515256
TI  - Opportunities and Challenges: Human Papillomavirus and Cancer.
AB  - Mucosal exposure to human papillomavirus (HPV) can lead to anogenital and head
      and neck (H&N) cancer. Vaccination at a young age can be almost 100% effective in
      preventing HPV infection with the viral subtypes in both men and women, at least
      for disease in the anogenital tract. Therapeutic strategies targeting HPV in
      cervical dysplasia and cancer are showing promise as well in regressing dysplasia
      and controlling disease. That HPV-positive H&N cancer is a different disease from
      HPV-negative disease, with different molecular and clinical features and
      prognosis, is becoming better appreciated. At this time, however, the NCCN
      Guidelines for H&N Cancers do not distinguish between the types. This is expected
      to change.

PMID- 28515257
TI  - Minimally Invasive Techniques for Treating Gynecologic Malignancies.
AB  - For many women with endometrial and cervical cancers, minimally invasive surgery
      represents an alternative standard of care to open abdominal procedures, with
      fewer complications, better postoperative quality of life, and overall lower
      cost. At the NCCN 22nd Annual Conference, Amanda N. Fader, MD, reviewed several
      minimally invasive strategies for treating gynecologic cancers, including
      conventional laparoscopy, robotic-assisted laparoscopy, sentinel lymph node
      technology, and single-port surgery; highlighted some of the contemporary
      literature on the role of these procedures; and explored some of the challenges
      and barriers to their successful performance.

PMID- 28515258
TI  - Evolving Treatment of Soft Tissue Sarcoma.
AB  - Soft tissue sarcomas comprise multiple histologic subtypes, occur at a number of
      anatomic sites, and require individualized treatment. Over the past 5 years, 4
      new drugs were approved for sarcoma, most of which are driven by histology or the
      anticipated response to treatment. Surgical resection remains the primary
      treatment for resectable tumors. For unresectable or metastatic disease,
      doxorubicin remains the backbone of chemotherapy, but other agents have improved
      on its single-agent efficacy. Chief among them is olaratumab, which, in
      combination with doxorubicin, is preferred over doxorubicin alone in the updated
      NCCN Clinical Practice Guidelines in Oncology for Soft Tissue Sarcoma.

PMID- 28515259
TI  - Novel Treatment Options for Neuroendocrine Tumors.
AB  - Neuroendocrine tumors (NETs) are not as rare as once thought, with a current
      prevalence that is estimated to be higher than that of many other
      gastrointestinal tumors. Multiple treatment options are available for these
      tumors, which are categorized according to their histology and site of origin.
      For patients with metastatic disease, somatostatin analogues are often the
      initial treatment, with other options considered when these drugs fail.

PMID- 28515260
TI  - Multigene Testing for Hereditary Cancer: When, Why, and How.
AB  - Multigene testing is a complicated area, with advantages and disadvantages of
      testing for hereditary cancer syndromes. Currently, NCCN does not endorse routing
      multiplex testing outside of a research setting, and/or intensive genetic
      counseling regarding risks and benefits. The 2017 NCCN Clinical Practice
      Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and
      Ovarian and Colorectal provide suggestions for mutation carriers identified by
      panel tests.

PMID- 28515261
TI  - Life After Treatment: Quality-of-Life Concerns in Patients Treated for Cancer.
AB  - Traditionally, the physical, psychological, and psychosocial long-term needs of
      cancer survivors have received little attention compared with screening for
      cancer recurrence and secondary cancers. The NCCN Clinical Practice Guidelines in
      Oncology (NCCN Guidelines) for Survivorship offer recommendations for various
      survivorship concerns, and those for improving menopausal symptoms were presented
      at the NCCN 22nd Annual Conference. Key considerations in managing menopausal
      symptoms in cancer survivors were reviewed, with chemotherapy-induced amenorrhea,
      fertility concerns, and both hormonal and nonhormonal therapeutic options
      featured.

PMID- 28515262
TI  - Smoking Cessation in Patients With Cancer: Treatment Advances and the
      Oncologist's Role.
AB  - The harms of smoking cigarettes are well-known, and the benefits of smoking
      cessation are well-established. Smoking cessation is especially important for
      patients with cancer, because smoking compromises the effects of cancer treatment
      and shortens survival. Interventions to achieve tobacco abstinence include
      pharmacotherapy and counseling, and these often must be repeated. Patients should
      be encouraged at every juncture to continue attempts to stop smoking.

PMID- 28515263
TI  - Ligand-induced activation of human TRPM2 requires the terminal ribose of ADPR and
      involves Arg1433 and Tyr1349.
AB  - TRPM2 (transient receptor potential channel, subfamily melastatin, member 2) is a
      Ca2+-permeable non-selective cation channel activated by the binding of adenosine
      5'-diphosphoribose (ADPR) to its cytoplasmic NUDT9H domain (NUDT9 homology
      domain). Activation of TRPM2 by ADPR downstream of oxidative stress has been
      implicated in the pathogenesis of many human diseases, rendering TRPM2 an
      attractive novel target for pharmacological intervention. However, the structural
      basis underlying this activation is largely unknown. Since ADP (adenosine 5'
      diphosphate) alone did not activate or antagonize the channel, we used a chemical
      biology approach employing synthetic analogues to focus on the role of the ADPR
      terminal ribose. All novel ADPR derivatives modified in the terminal ribose,
      including that with the seemingly minor change of methylating the anomeric-OH,
      abolished agonist activity at TRPM2. Antagonist activity improved as the terminal
      substituent increasingly resembled the natural ribose, indicating that gating by
      ADPR might require specific interactions between hydroxyl groups of the terminal
      ribose and the NUDT9H domain. By mutating amino acid residues of the NUDT9H
      domain, predicted by modelling and docking to interact with the terminal ribose,
      we demonstrate that abrogating hydrogen bonding of the amino acids Arg1433 and
      Tyr1349 interferes with activation of the channel by ADPR. Taken together, using
      the complementary experimental approaches of chemical modification of the ligand
      and site-directed mutagenesis of TRPM2, we demonstrate that channel activation
      critically depends on hydrogen bonding of Arg1433 and Tyr1349 with the terminal
      ribose. Our findings allow for a more rational design of novel TRPM2 antagonists
      that may ultimately lead to compounds of therapeutic potential.

PMID- 28515264
TI  - Functional characterization of the copper transcription factor AfMac1 from
      Aspergillus fumigatus.
AB  - Although copper functions as a cofactor in many physiological processes, copper
      overload leads to harmful effects in living cells. Thus, copper homeostasis is
      tightly regulated. However, detailed copper metabolic pathways have not yet been
      identified in filamentous fungi. In this report, we investigated the copper
      transcription factor AfMac1 ( Aspergillus fumigatusMac1 homolog) and identified
      its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA
      binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae, and
      AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1
      resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1
      failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of
      A. fumigatus failed to grow in copper-limited media, and its growth was restored
      by introducing ctrC We found that AfMac1 specifically bound to the promoter
      region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was
      identified from the promoter region of ctrC, and the addition of mutant ctrC
      lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus
      Furthermore, deletion of Afmac1 significantly reduced strain virulence and
      activated conidial killing activity by neutrophils and macrophages. Taken
      together, these results suggest that AfMac1 is a copper transcription factor that
      regulates cellular copper homeostasis in A. fumigatus.

PMID- 28515265
TI  - Clinical marker for Alzheimer disease pathology in logopenic primary progressive
      aphasia.
AB  - OBJECTIVE: To determine whether logopenic features of phonologic loop dysfunction
      reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia
      (PPA). METHODS: We performed a retrospective case-control study of 34 patients
      with PPA with available autopsy tissue. We compared baseline and longitudinal
      clinical features in patients with primary AD neuropathology to those with
      primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in
      pathology-defined groups using postmortem neuropathologic data. RESULTS: A total
      of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13
      frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%)
      patients with AD had a logopenic spectrum phenotype; 5 met published criteria for
      the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits
      (lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA-). Sentence
      repetition was impaired in 68% of patients with PPA with AD pathology; forward
      digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA
      (33%, p < 0.01). Lexical retrieval difficulty was common in all patients with PPA
      and did not discriminate between groups. Compared to non-AD, PPA with AD
      pathology had elevated microscopic neurodegenerative pathology in the
      superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (p < 0.01). Low
      DF scores correlated with high microscopic pathologic burden in
      superior/midtemporal and angular gyri (p <= 0.03). CONCLUSIONS: Phonologic loop
      dysfunction is a central feature of AD-associated PPA and specifically correlates
      with temporoparietal neurodegeneration. Quantitative measures of phonologic loop
      function, combined with modified clinical lvPPA criteria, may help discriminate
      AD-associated PPA.

PMID- 28515267
TI  - Presurgical thalamic "hubness" predicts surgical outcome in temporal lobe
      epilepsy.
AB  - OBJECTIVE: To characterize the presurgical brain functional architecture
      presented in patients with temporal lobe epilepsy (TLE) using graph theoretical
      measures of resting-state fMRI data and to test its association with surgical
      outcome. METHODS: Fifty-six unilateral patients with TLE, who subsequently
      underwent anterior temporal lobectomy and were classified as obtaining a seizure
      free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21)
      outcome at 1 year after surgery, and 28 matched healthy controls were enrolled.
      On the basis of their presurgical resting-state functional connectivity, network
      properties, including nodal hubness (importance of a node to the network; degree,
      betweenness, and eigenvector centralities) and integration (global efficiency),
      were estimated and compared across our experimental groups. Cross-validations
      with support vector machine (SVM) were used to examine whether selective nodal
      hubness exceeded standard clinical characteristics in outcome prediction.
      RESULTS: Compared to the seizure-free patients and healthy controls, the not
      seizure-free patients displayed a specific increase in nodal hubness (degree and
      eigenvector centralities) involving both the ipsilateral and contralateral
      thalami, contributed by an increase in the number of connections to regions
      distributed mostly in the contralateral hemisphere. Simulating removal of
      thalamus reduced network integration more dramatically in not seizure-free
      patients. Lastly, SVM models built on these thalamic hubness measures produced
      76% prediction accuracy, while models built with standard clinical variables
      yielded only 58% accuracy (both were cross-validated). CONCLUSIONS: A thalamic
      network associated with seizure recurrence may already be established
      presurgically. Thalamic hubness can serve as a potential biomarker of surgical
      outcome, outperforming the clinical characteristics commonly used in epilepsy
      surgery centers.

PMID- 28515266
TI  - Total small vessel disease score and risk of recurrent stroke: Validation in 2
      large cohorts.
AB  - OBJECTIVE: In patients with TIA and ischemic stroke, we validated the total small
      vessel disease (SVD) score by determining its prognostic value for recurrent
      stroke. METHODS: Two independent prospective studies were conducted, one
      comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford
      Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic
      stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed
      for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular
      spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke
      was determined and potential refinements considered. RESULTS: In 2,002 patients
      with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years
      follow-up), a higher score was associated with an increased risk of recurrent
      ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16-1.51, p
      < 0.0001; c statistic 0.61, 0.56-0.65, p < 0.0001) and intracerebral hemorrhage
      (ICH) (HR 1.54, 1.11-2.13, p = 0.009; c statistic 0.65, 0.54-0.76, p = 0.006). A
      higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke
      subtypes (c statistic 0.67, 0.59-0.74, p < 0.0001 and 0.60, 0.55-0.65, p <
      0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of
      basal ganglia PVS potentially improved predictive power for ICH (c statistic
      0.71, 0.60-0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic
      0.60, 0.56-0.65, phet = 0.76) on internal validation. CONCLUSIONS: The total SVD
      score has predictive value for recurrent stroke after TIA/ischemic stroke.
      Prediction of recurrence in patients with nonlacunar events highlights the
      potential role of SVD in wider stroke etiology.

PMID- 28515268
TI  - Benefits, pitfalls, and future design of population-based registers in
      neurodegenerative disease.
AB  - Population-based disease registers identify and characterize all cases of
      disease, including those that might otherwise be neglected. Prospective
      population-based registers in neurodegeneration are necessary to provide
      comprehensive data on the whole phenotypic spectrum and can guide planning of
      health services. With the exception of the rare disease amyotrophic lateral
      sclerosis, few complete population-based registers exist for neurodegenerative
      conditions. Incomplete ascertainment, limitations and uncertainty in diagnostic
      categorization, and failure to recognize sources of bias reduce the accuracy and
      usefulness of many registers. Common biases include population stratification,
      the use of prevalent rather than incident cases in earlier years, changes in
      disease understanding and diagnostic criteria, and changing demographics over
      time. Future registers are at risk of funding shortfalls and changes to privacy
      legislation. Notwithstanding, as heterogeneities of clinical phenotype and
      disease pathogenesis are increasingly recognized in the neurodegenerations, well
      designed longitudinal population-based disease registers will be an essential
      requirement to complete clinical understanding of neurodegenerative diseases.

PMID- 28515269
TI  - Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month
      pilot trial.
AB  - OBJECTIVE: To test the hypothesis that 12 months of seal oil omega-3
      polyunsaturated fatty acids (omega-3 PUFA) supplementation will stop the known
      progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes
      mellitus (T1DM). METHODS: Individuals with T1DM and evidence of DSP as determined
      by a Toronto Clinical Neuropathy Score >=1 were recruited to participate in a
      single-arm, open-label trial of seal oil omega-3 PUFA supplementation (10 mL.d-1;
      750 mg eicosapentaenoic acid, 560 mg docosapentaenoic acid, and 1,020 mg
      docosahexaenoic acid) for 1 year. The primary outcome was the 1-year change in
      corneal nerve fiber length (CNFL) measured by in vivo corneal confocal
      microscopy, with sensory and nerve conduction measures as secondary outcomes.
      RESULTS: Forty participants (53% female), aged 48 +/- 14 years, body mass index
      28.1 +/- 5.8 with diabetes duration of 27 +/- 18 years, were enrolled. At
      baseline, 23 participants had clinical DSP and 17 did not. Baseline CNFL was 8.3
      +/- 2.9 mm/mm2 and increased 29% to 10.1 +/- 3.7 mm/mm2 (p = 0.002) after 12
      months of supplementation. There was no change in nerve conduction or sensory
      function. CONCLUSIONS: Twelve months of omega-3 supplementation was associated
      with increase in CNFL in T1DM. CLINICALTRIALSGOVIDENTIFIER: NCT02034266.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for
      patients with T1DM and evidence of DSP, 12 months of seal oil omega-3
      supplementation increases CNFL.

PMID- 28515271
TI  - Imaging-based selection of patients for acute stroke treatment: Is it ready for
      prime time?

PMID- 28515270
TI  - Evaluation of hyperacute infarct volume using ASPECTS and brain CT perfusion core
      volume.
AB  - OBJECTIVE: To compare the accuracy of Alberta Stroke Program Early Computed
      Tomography Score (ASPECTS) and CT perfusion to detect established infarction in
      acute anterior circulation stroke. METHODS: We performed an observational study
      in 59 acute anterior circulation ischemic stroke patients who underwent brain
      noncontrast CT, CT perfusion, and MRI within 100 minutes from CT imaging. ASPECTS
      scores were calculated by 4 blinded vascular neurologists. The accuracy of
      ASPECTS and CT perfusion core volume to detect an acute MRI diffusion lesion of
      >=70 mL was evaluated using receiver operating characteristics analysis and
      optimum cutoff values were calculated using Youden J. RESULTS: Median ASPECTS
      score was 8 (interquartile range [IQR] 5-9). Median CT perfusion core volume was
      22 mL (IQR 10.4-71.9). Median MRI diffusion lesion volume was 24.5 mL (IQR 10
      63.9). No significant difference was found between the accuracy of CT perfusion
      and ASPECTS (c statistic 0.95 vs 0.87, p value for difference = 0.17). The
      optimum ASPECTS cutoff score to detect a diffusion-weighted imaging lesion >=70
      mL was <7 (sensitivity 0.74, specificity 0.86, Youden J = 0.60) and the optimum
      CT perfusion core volume cutoff was >=50 mL (sensitivity 0.86, specificity 0.97,
      Youden J = 0.84). The CT perfusion core lesion covered a median of 100% (IQR 86%
      100%) of the acute MRI lesion volume (Pearson R = 0.88; R2 = 0.77). CONCLUSIONS:
      We found no significant difference between the accuracy of CT perfusion and
      ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.

PMID- 28515273
TI  - Thalamus as a "hub" to predict outcome after epilepsy surgery.

PMID- 28515272
TI  - Racial disparities in neurologic health care access and utilization in the United
      States.
AB  - OBJECTIVE: To evaluate racial and ethnic differences in the utilization of
      neurologic care across a wide range of neurologic conditions in the United
      States. METHODS: We analyzed nationally representative data from the 2006-2013
      Medical Expenditure Panel Survey (MEPS), including information on demographics,
      patient-reported health conditions, neurology visit rates, and costs. Using
      diagnostic codes, we identified persons with any self-identified neurologic
      disorder except back pain, as well as 5 subgroups (Parkinson disease, multiple
      sclerosis, headache, cerebrovascular disease, and epilepsy). To assess
      disparities in neurologic care utilization, we performed logistic regression
      analyses of outpatient department neurologic care visit rates and expenditures
      for each racial ethnic group controlling for age, sex, health status,
      socioeconomic characteristics, and geographic region of care. RESULTS: Of the
      279,103 MEPS respondents, 16,936 (6%) self-reported a neurologic condition; 5,890
      (2%) received a total of 13,685 outpatient neurology visits. Black participants
      were nearly 30% less likely to see an outpatient neurologist (odds ratio [OR]
      0.72, confidence interval [CI] 0.64-0.81) relative to their white counterparts,
      even after adjustment for demographic, insurance, and health status differences.
      Hispanic participants were 40% less likely to see an outpatient neurologist (OR
      0.61, CI 0.54-0.69). Among participants with known neurologic conditions, blacks
      were more likely to be cared for in the emergency department, to have more
      hospital stays, and to have higher per capita inpatient expenditures than their
      white counterparts. CONCLUSIONS: Our findings highlight racial and ethnic
      inequalities in the utilization of neurologic care in the United States.

PMID- 28515274
TI  - Beyond clinical syndromes in primary progressive aphasia: Seeking etiologic
      diagnoses.

PMID- 28515275
TI  - Autophagy in the presynaptic compartment in health and disease.
AB  - Synapses are functionally distinct neuronal compartments that are critical for
      brain function, with synaptic dysfunction being an early pathological feature in
      aging and disease. Given the large number of proteins needed for synaptic
      function, the proliferation of defective proteins and the subsequent loss of
      protein homeostasis may be a leading cause of synaptic dysfunction. Autophagic
      mechanisms are cellular digestion processes that recycle cellular components and
      contribute to protein homeostasis. Autophagy is important within the nervous
      system, but its function in specific compartments such as the synapse has been
      unclear. Evidence from research on both autophagy and synaptic function suggests
      that there are links between the two and that synaptic homeostasis during aging
      requires autophagy to regulate protein homeostasis. Exciting new work on
      autophagy-modulating proteins that are enriched at the synapse has begun to link
      autophagy to synapses and synaptic dysfunction in disease. A better understanding
      of these links will help us harness the potential therapeutic benefits of
      autophagy in combating age-related disorders of the nervous system.

PMID- 28515276
TI  - Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP
      chaperones.
AB  - Splicing is catalyzed by the spliceosome, a complex of five major small nuclear
      ribonucleoprotein particles (snRNPs). The pre-mRNA splicing factor PRPF8 is a
      crucial component of the U5 snRNP, and together with EFTUD2 and SNRNP200, it
      forms a central module of the spliceosome. Using quantitative proteomics, we
      identified assembly intermediates containing PRPF8, EFTUD2, and SNRNP200 in
      association with the HSP90/R2TP complex, its ZNHIT2 cofactor, and additional
      proteins. HSP90 and R2TP bind unassembled U5 proteins in the cytoplasm, stabilize
      them, and promote the formation of the U5 snRNP. We further found that PRPF8
      mutants causing Retinitis pigmentosa assemble less efficiently with the U5 snRNP
      and bind more strongly to R2TP, with one mutant retained in the cytoplasm in an
      R2TP-dependent manner. We propose that the HSP90/R2TP chaperone system promotes
      the assembly of a key module of U5 snRNP while assuring the quality control of
      PRPF8. The proteomics data further reveal new interactions between R2TP and the
      tuberous sclerosis complex (TSC), pointing to a potential link between growth
      signals and the assembly of key cellular machines.

PMID- 28515279
TI  - Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.
AB  - Eosinophils have the capacity to regulate the function of T cell subsets. Our aim
      was to test the hypothesis of the existence of a regulatory subset of
      eosinophils. Human eosinophils were incubated with T cells that were stimulated
      with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11%
      of the eosinophils gained CD16 expression. A CD16hi subset of eosinophils,
      encompassing 1-5% of all eosinophils, was also identified in the blood of healthy
      subjects. FACS sorting showed that these CD16hi eosinophils were significantly
      stronger suppressors of T cell proliferation than were conventional CD16neg
      eosinophils. Human eosinophils contain stores of the immunoregulatory protein
      galectin-10. We found that Ab-mediated neutralization of galectin-10 partially
      abrogated the suppressive function of the eosinophils. Moreover, recombinant
      galectin-10 by itself was able to suppress T cell proliferation. Finally, we
      detected galectin-10-containing immune synapses between eosinophils and
      lymphocytes. To conclude, we describe a subset of suppressive eosinophils
      expressing CD16 that may escape detection because CD16-based negative selection
      is the standard procedure for the isolation of human eosinophils. Moreover, we
      show that galectin-10 functions as a T cell-suppressive molecule in eosinophils.

PMID- 28515278
TI  - Critical Role of P2Y12 Receptor in Regulation of Th17 Differentiation and
      Experimental Autoimmune Encephalomyelitis Pathogenesis.
AB  - Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can
      activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to
      be associated with inflammation, but its function in T cell differentiation and
      autoimmune diseases pathogenesis is unclear. In this study, we found that the
      P2Y12 receptor was upregulated in the peripheral immune tissues of experimental
      autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y12 led to a reduced
      peak severity and cumulative disease score in EAE mice, followed by a dramatic
      reduction of leukocyte infiltration and less extensive demyelination. The
      percentage of Th17, one of the main pathogenic T cells in EAE, was sharply
      decreased in P2Y12 knockout mice, accompanied by decreased IL-17A production and
      a low mRNA level of Th17-related genes. In vitro culture assay further verified
      that P2Y12 directly regulated Th17 differentiation. More interestingly,
      clopidogrel and ticagrelor, two P2Y12-specific antagonists, effectively
      alleviated the disease severity of EAE and inhibited Th17 differentiation both in
      vivo and in vitro. Further study demonstrated that blocking the P2Y12 receptor
      also ameliorated the symptoms of 2,4,6-trinitrobenzenesulfonic acid-induced
      colitis and multiple low-dose streptozocin-induced type 1 diabetes. Our findings
      not only revealed the critical role of P2Y12 in Th17 differentiation and EAE
      pathogenesis, but also suggested the promising potential of P2Y12 antagonists in
      the treatment of autoimmune diseases.

PMID- 28515280
TI  - Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model
      of Allergic Asthma.
AB  - Although glucocorticoids (GCs) are a mainstay in the clinical management of
      asthma, the target cells that mediate their therapeutic effects are unknown.
      Contrary to our expectation, we found that GC receptor (GR) expression in immune
      cells was dispensable for successful therapy of allergic airway inflammation
      (AAI) with dexamethasone. Instead, GC treatment was compromised in mice
      expressing a defective GR in the nonhematopoietic compartment or selectively
      lacking the GR in airway epithelial cells. Further, we found that an intact GR
      dimerization interface was a prerequisite for the suppression of AAI and airway
      hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to
      modulate gene expression in airway epithelial cells coincided with its potency to
      resolve AAI supports a crucial role for transcriptional regulation by the GR in
      this cell type. Taken together, we identified an unknown mode of GC action in the
      treatment of allergic asthma that might help to develop more specific therapies
      in the future.

PMID- 28515277
TI  - Histone chaperone HIRA regulates neural progenitor cell proliferation and
      neurogenesis via beta-catenin.
AB  - Histone cell cycle regulator (HIRA) is a histone chaperone and has been
      identified as an epigenetic regulator. Subsequent studies have provided evidence
      that HIRA plays key roles in embryonic development, but its function during early
      neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in
      neural progenitor cells, and HIRA knockdown reduces neural progenitor cell
      proliferation, increases terminal mitosis and cell cycle exit, and ultimately
      results in premature neuronal differentiation. Additionally, we demonstrate that
      HIRA enhances beta-catenin expression by recruiting H3K4 trimethyltransferase
      Setd1A, which increases H3K4me3 levels and heightens the promoter activity of
      beta-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or
      beta-catenin can override neurogenesis abnormities caused by HIRA defects.
      Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates
      beta-catenin expression and then regulates neurogenesis. This finding represents
      a novel epigenetic mechanism underlying the histone code and has profound and
      lasting implications for diseases and neurobiology.

PMID- 28515281
TI  - CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived
      Dendritic Cells and Increases Stimulation of T Cells.
AB  - Chemokines have been shown to play immune-modulatory functions unrelated to
      steering cell migration. CXCL4 is a chemokine abundantly produced by activated
      platelets and immune cells. Increased levels of circulating CXCL4 are associated
      with immune-mediated conditions, including systemic sclerosis. Considering the
      central role of dendritic cells (DCs) in immune activation, in this article we
      addressed the effect of CXCL4 on the phenotype and function of monocyte-derived
      DCs (moDCs). To this end, we compared innate and adaptive immune responses of
      moDCs with those that were differentiated in the presence of CXCL4. Already prior
      to TLR- or Ag-specific stimulation, CXCL4-moDCs displayed a more matured
      phenotype. We found that CXCL4 exposure can sensitize moDCs for TLR-ligand
      responsiveness, as illustrated by a dramatic upregulation of CD83, CD86, and MHC
      class I in response to TLR3 and TLR7/8-agonists. Also, we observed a markedly
      increased secretion of IL-12 and TNF-alpha by CXCL4-moDCs exclusively upon
      stimulation with polyinosinic-polycytidylic acid, R848, and CL075 ligands. Next,
      we analyzed the effect of CXCL4 in modulating DC-mediated T cell activation.
      CXCL4-moDCs strongly potentiated proliferation of autologous CD4+ T cells and
      CD8+ T cells and production of IFN-gamma and IL-4, in an Ag-independent manner.
      Although the internalization of Ag was comparable to that of moDCs, Ag processing
      by CXCL4-moDCs was impaired. Yet, these cells were more potent at stimulating Ag
      specific CD8+ T cell responses. Together our data support that increased levels
      of circulating CXCL4 may contribute to immune dysregulation through the
      modulation of DC differentiation.

PMID- 28515283
TI  - Anisomorphic cortical reorganization in asymmetric sensorineural hearing loss.
AB  - Acoustic trauma or inner ear disease may predominantly injure one ear, causing
      asymmetric sensorineural hearing loss (SNHL). While characteristic frequency (CF)
      map plasticity of primary auditory cortex (AI) contralateral to the injured ear
      has been detailed, there is no study that also evaluates ipsilateral AI to
      compare cortical reorganization across both hemispheres. We assess whether the
      normal isomorphic mirror-image relationship between the two hemispheres is
      maintained or disrupted in mild-to-moderate asymmetric SNHL of adult squirrel
      monkeys. At week 24 after induction of acoustic injury to the right ear,
      functional organization of the two hemispheres differs in direction and magnitude
      of interaural CF difference, percentage of recording sites with spectrally
      nonoverlapping binaural activation, and the concurrence of peripheral and central
      activation thresholds. The emergence of this anisomorphic cortical reorganization
      of the two hemispheres is replicated by simulation based on spike timing
      dependent plasticity, where 1) AI input from the contralateral ear is dominant,
      2) reestablishment of relatively shorter contralateral ear input timing drives
      reorganization, and 3) only AI contralateral to the injured ear undergoes major
      realignment of interaural frequency maps that evolve over months. Asymmetric SNHL
      disrupts isomorphic organization between the two hemispheres and results in
      relative local hemispheric autonomy, potentially impairing performance of tasks
      that require binaural input alignment or interhemispheric processing.NEW &
      NOTEWORTHY Mild-to-moderate hearing loss in one ear and essentially normal
      hearing in the other triggers cortical reorganization that is different in the
      two hemispheres. Asymmetry of cochlea sensitivities does not simply propagate to
      the two auditory cortices in mirror-image fashion. The resulting anisomorphic
      cortical reorganization may be a neurophysiological basis of clinical deficits in
      asymmetric hearing loss, such as difficulty with hearing in noise, impaired
      spatial hearing, and accelerated decline of the poorer ear.

PMID- 28515284
TI  - Long-lasting increase in axonal excitability after epidurally applied DC.
AB  - Effects of direct current (DC) on nerve fibers have primarily been investigated
      during or just after DC application. However, locally applied cathodal DC was
      recently demonstrated to increase the excitability of intraspinal preterminal
      axonal branches for >1 h. The aim of this study was therefore to investigate
      whether DC evokes a similarly long-lasting increase in the excitability of
      myelinated axons within the dorsal columns. The excitability of dorsal column
      fibers stimulated epidurally was monitored by recording compound action
      potentials in peripheral nerves in acute experiments in deeply anesthetized rats.
      The results show that 1) cathodal polarization (0.8-1.0 uA) results in a
      severalfold increase in the number of epidurally activated fibers and 2) the
      increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is
      activity independent, as it does not require fiber stimulation during the
      polarization. These features demonstrate an unexplored form of plasticity of
      myelinated fibers and indicate the conditions under which it develops. They also
      suggest that therapeutic effects of epidural stimulation may be significantly
      enhanced if it is combined with DC polarization. In particular, by using DC to
      increase the number of fibers activated by low-intensity epidural stimuli, the
      low clinical tolerance to higher stimulus intensities might be overcome. The
      activity independence of long-lasting DC effects would also allow the use of only
      brief periods of DC polarization preceding epidural stimulation to increase the
      effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of
      myelinated fibers. The differences in time course of DC-evoked increases in the
      excitability of myelinated nerve fibers in the dorsal columns and in preterminal
      axonal branches suggest that distinct mechanisms are involved in them. The
      results show that combining epidural stimulation and transspinal DC polarization
      may dramatically improve their outcome and result in more effective pain control
      and the return of impaired motor functions.

PMID- 28515282
TI  - Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.
AB  - Talin, a cytoskeletal protein essential in mediating integrin activation, has
      been previously shown to be involved in the regulation of T cell proliferation
      and function. In this study, we describe a role for talin in maintaining the
      homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific
      deletion of talin in Tln1fl/flCd4Cre mice resulted in spontaneous lymphocyte
      activation, primarily due to numerical and functional deficiencies of Treg cells
      in the periphery. Peripheral talin-deficient Treg cells were unable to maintain
      high expression of IL-2Ralpha, resulting in impaired IL-2 signaling and
      ultimately leading to increased apoptosis through downregulation of prosurvival
      proteins Bcl-2 and Mcl-1. The requirement for talin in maintaining high IL
      2Ralpha expression by Treg cells was due, in part, to integrin LFA-1-mediated
      interactions between Treg cells and dendritic cells. Collectively, our data
      suggest a critical role for talin in Treg cell-mediated maintenance of immune
      homeostasis.

PMID- 28515285
TI  - Cortical amplification models of experience-dependent development of selective
      columns and response sparsification.
AB  - The development of direction-selective cortical columns requires visual
      experience, but the neural circuits and plasticity mechanisms that are
      responsible for this developmental transition are unknown. To gain insight into
      the mechanisms that could underlie experience-dependent increases in selectivity,
      we explored families of cortical amplifier models that enhance weakly biased
      feedforward signals. Here we focused exclusively on possible contributions of
      cortico-cortical connections and took feedforward input to be constant. We
      modeled pairs of interconnected columns that received equal and oppositely biased
      inputs. In a single-element model of cortical columns, we found two ways that
      cortical columns could receive biased feedforward input and exhibit strong but
      unselective responses to stimuli: 1) within-column recurrent excitatory
      connections could be strong enough to amplify both strong and weak feedforward
      input, or 2) columns that received differently biased inputs could have strong
      excitatory cross-connections that destroy selectivity. A Hebbian plasticity rule
      combined with simulated experience with stimuli weakened these strong cross
      connections across cortical columns, allowing the individual columns to respond
      selectively to their biased inputs. In a model that included both excitatory and
      inhibitory neurons in each column, an additional means of obtaining selectivity
      through the cortical circuit was uncovered: cross-column suppression of
      inhibition-stabilized networks. When each column operated as an inhibition
      stabilized network, cross-column excitation onto inhibitory neurons forced
      competition between the columns but in a manner that did not involve strong null
      direction inhibition, consistent with experimental measurements of direction
      selectivity in visual cortex. Experimental predictions of these possible
      contributions of cortical circuits are discussed.NEW & NOTEWORTHY Sensory
      circuits are initially constructed via mechanisms that are independent of sensory
      experience, but later refinement requires experience. We constructed models of
      how circuits that receive biased feedforward inputs can be initially unselective
      and then be modified by experience and plasticity so that the resulting circuit
      exhibits increased selectivity. We propose that neighboring cortical columns may
      initially exhibit coupling that is too strong for selectivity. Experience
      dependent mechanisms decrease this coupling so individual columns can exhibit
      selectivity.

PMID- 28515286
TI  - Responses of Purkinje cells in the oculomotor vermis of monkeys during smooth
      pursuit eye movements and saccades: comparison with floccular complex.
AB  - We recorded the responses of Purkinje cells in the oculomotor vermis during
      smooth pursuit and saccadic eye movements. Our goal was to characterize the
      responses in the vermis using approaches that would allow direct comparisons with
      responses of Purkinje cells in another cerebellar area for pursuit, the floccular
      complex. Simple-spike firing of vermis Purkinje cells is direction selective
      during both pursuit and saccades, but the preferred directions are sufficiently
      independent so that downstream circuits could decode signals to drive pursuit and
      saccades separately. Complex spikes also were direction selective during pursuit,
      and almost all Purkinje cells showed a peak in the probability of complex spikes
      during the initiation of pursuit in at least one direction. Unlike the floccular
      complex, the preferred directions for simple spikes and complex spikes were not
      opposite. The kinematics of smooth eye movement described the simple-spike
      responses of vermis Purkinje cells well. Sensitivities were similar to those in
      the floccular complex for eye position and considerably lower for eye velocity
      and acceleration. The kinematic relations were quite different for saccades vs.
      pursuit, supporting the idea that the contributions from the vermis to each kind
      of movement could contribute independently in downstream areas. Finally, neither
      the complex-spike nor the simple-spike responses of vermis Purkinje cells were
      appropriate to support direction learning in pursuit. Complex spikes were not
      triggered reliably by an instructive change in target direction; simple-spike
      responses showed very small amounts of learning. We conclude that the vermis
      plays a different role in pursuit eye movements compared with the floccular
      complex.NEW & NOTEWORTHY The midline oculomotor cerebellum plays a different role
      in smooth pursuit eye movements compared with the lateral, floccular complex and
      appears to be much less involved in direction learning in pursuit. The output
      from the oculomotor vermis during pursuit lies along a null-axis for saccades and
      vice versa. Thus the vermis can play independent roles in the two kinds of eye
      movement.

PMID- 28515288
TI  - Motor recovery beginning 23 years after ischemic stroke.
AB  - It is widely believed that most stroke recovery occurs within 6 mo, with little
      benefit of physiotherapy or other modalities beyond 1 yr. We report a remarkable
      case of stroke recovery beginning 23 yr after a severe stroke due to embolization
      from the innominate artery and subclavian artery, resulting from compression of
      the right subclavian artery by a cervical rib. The patient had a large right
      frontoparietal infarction with severe left hemiparesis and a totally
      nonfunctional spastic left hand. He experienced some recovery of hand function
      that began 23 yr after the stroke, 1 yr after he took up regular swimming. As a
      result, intensive physiotherapy was initiated, with repetitive large muscle
      movement and a spring-loaded mechanical orthosis that provides resistance to
      finger flexors and supports finger extensors. Within 2 yr, he could pick up coins
      with the previously useless left hand. Functional MRI studies document widespread
      distribution of the recovery in both hemispheres. This case provides impetus not
      only to more intensive and prolonged physiotherapy, but also to treatment with
      emerging modalities such as stem cell therapy and exosome and microRNA
      therapies.NEW & NOTEWORTHY Widespread bilateral activation of both sides of the
      cerebrum and cerebellum are demonstrated on functional MRI after motor recovery
      of a completely nonfunctional left hand that began 23 yr after a severe stroke.
      This suggests that the generally accepted window of recovery beyond which further
      therapy is not indicated should be entirely reconsidered. Physiotherapy and new
      modalities in development might be indicated long after a stroke.

PMID- 28515287
TI  - Context effects on smooth pursuit and manual interception of a disappearing
      target.
AB  - In our natural environment, we interact with moving objects that are surrounded
      by richly textured, dynamic visual contexts. Yet most laboratory studies on
      vision and movement show visual objects in front of uniform gray backgrounds.
      Context effects on eye movements have been widely studied, but it is less well
      known how visual contexts affect hand movements. Here we ask whether eye and hand
      movements integrate motion signals from target and context similarly or
      differently, and whether context effects on eye and hand change over time. We
      developed a track-intercept task requiring participants to track the initial
      launch of a moving object ("ball") with smooth pursuit eye movements. The ball
      disappeared after a brief presentation, and participants had to intercept it in a
      designated "hit zone." In two experiments (n = 18 human observers each), the ball
      was shown in front of a uniform or a textured background that either was
      stationary or moved along with the target. Eye and hand movement latencies and
      speeds were similarly affected by the visual context, but eye and hand
      interception (eye position at time of interception, and hand interception timing
      error) did not differ significantly between context conditions. Eye and hand
      interception timing errors were strongly correlated on a trial-by-trial basis
      across all context conditions, highlighting the close relation between these
      responses in manual interception tasks. Our results indicate that visual contexts
      similarly affect eye and hand movements but that these effects may be short
      lasting, affecting movement trajectories more than movement end points.NEW &
      NOTEWORTHY In a novel track-intercept paradigm, human observers tracked a briefly
      shown object moving across a textured, dynamic context and intercepted it with
      their finger after it had disappeared. Context motion significantly affected eye
      and hand movement latency and speed, but not interception accuracy; eye and hand
      position at interception were correlated on a trial-by-trial basis. Visual
      context effects may be short-lasting, affecting movement trajectories more than
      movement end points.

PMID- 28515289
TI  - Learning temporal context shapes prestimulus alpha oscillations and improves
      visual discrimination performance.
AB  - Time is an inseparable component of every physical event that we perceive, yet it
      is not clear how the brain processes time or how the neuronal representation of
      time affects our perception of events. Here we asked subjects to perform a visual
      discrimination task while we changed the temporal context in which the stimuli
      were presented. We collected electroencephalography (EEG) signals in two temporal
      contexts. In predictable blocks stimuli were presented after a constant delay
      relative to a visual cue, and in unpredictable blocks stimuli were presented
      after variable delays relative to the visual cue. Four subsecond delays of 83,
      150, 400, and 800 ms were used in the predictable and unpredictable blocks. We
      observed that predictability modulated the power of prestimulus alpha
      oscillations in the parieto-occipital sites: alpha power increased in the 300-ms
      window before stimulus onset in the predictable blocks compared with the
      unpredictable blocks. This modulation only occurred in the longest delay period,
      800 ms, in which predictability also improved the behavioral performance of the
      subjects. Moreover, learning the temporal context shaped the prestimulus alpha
      power: modulation of prestimulus alpha power grew during the predictable block
      and correlated with performance enhancement. These results suggest that the brain
      is able to learn the subsecond temporal context of stimuli and use this to
      enhance sensory processing. Furthermore, the neural correlate of this temporal
      prediction is reflected in the alpha oscillations.NEW & NOTEWORTHY It is not well
      understood how the uncertainty in the timing of an external event affects its
      processing, particularly at subsecond scales. Here we demonstrate how a
      predictable timing scheme improves visual processing. We found that learning the
      predictable scheme gradually shaped the prestimulus alpha power. These findings
      indicate that the human brain is able to extract implicit subsecond patterns in
      the temporal context of events.

PMID- 28515290
TI  - A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a
      Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model.
AB  - Rotavirus infection is one of the most common causes of diarrheal illness in
      humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA),
      a disease resulting in inflammatory obstruction of the extrahepatic biliary tract
      and intrahepatic bile ducts. We previously showed that the amino acid arginine
      (R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is
      required for viral binding and entry into biliary epithelial cells. To determine
      if this single amino acid (R) influences the pathogenicity of the virus, we
      generated a recombinant virus with a single amino acid mutation at this site
      through a reverse genetics system. We demonstrated that the RRV mutant (RRVVP4
      R446G) produced less symptomatology and replicated to lower titers both in vivo
      and in vitro than those seen with wild-type RRV, with reduced binding in
      cholangiocytes. Our results demonstrate that a single amino acid change in the
      RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in
      mice.IMPORTANCE Rotavirus is the leading cause of diarrhea in humans. Rhesus
      rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in
      mice. We developed a reverse genetics system to create a mutant of RRV (RRVVP4
      R446G) with a single amino acid change in the VP4 protein compared to that of
      wild-type RRV. In vitro, the mutant virus had reduced binding and infectivity in
      cholangiocytes. In vivo, it produced fewer symptoms and lower mortality in
      neonatal mice, resulting in an attenuated form of biliary atresia.

PMID- 28515291
TI  - Differential Disease Susceptibilities in Experimentally Reptarenavirus-Infected
      Boa Constrictors and Ball Pythons.
AB  - Inclusion body disease (IBD) is an infectious disease originally described in
      captive snakes. It has traditionally been diagnosed by the presence of large
      eosinophilic cytoplasmic inclusions and is associated with neurological,
      gastrointestinal, and lymphoproliferative disorders. Previously, we identified
      and established a culture system for a novel lineage of arenaviruses isolated
      from boa constrictors diagnosed with IBD. Although ample circumstantial evidence
      suggested that these viruses, now known as reptarenaviruses, cause IBD, there has
      been no formal demonstration of disease causality since their discovery. We
      therefore conducted a long-term challenge experiment to test the hypothesis that
      reptarenaviruses cause IBD. We infected boa constrictors and ball pythons by
      cardiac injection of purified virus. We monitored the progression of viral growth
      in tissues, blood, and environmental samples. Infection produced dramatically
      different disease outcomes in snakes of the two species. Ball pythons infected
      with Golden Gate virus (GoGV) and with another reptarenavirus displayed severe
      neurological signs within 2 months, and viral replication was detected only in
      central nervous system tissues. In contrast, GoGV-infected boa constrictors
      remained free of clinical signs for 2 years, despite high viral loads and the
      accumulation of large intracellular inclusions in multiple tissues, including the
      brain. Inflammation was associated with infection in ball pythons but not in boa
      constrictors. Thus, reptarenavirus infection produces inclusions and inclusion
      body disease, although inclusions per se are neither necessarily associated with
      nor required for disease. Although the natural distribution of reptarenaviruses
      has yet to be described, the different outcomes of infection may reflect
      differences in geographical origin.IMPORTANCE New DNA sequencing technologies
      have made it easier than ever to identify the sequences of microorganisms in
      diseased tissues, i.e., to identify organisms that appear to cause disease, but
      to be certain that a candidate pathogen actually causes disease, it is necessary
      to provide additional evidence of causality. We have done this to demonstrate
      that reptarenaviruses cause inclusion body disease (IBD), a serious transmissible
      disease of snakes. We infected boa constrictors and ball pythons with purified
      reptarenavirus. Ball pythons fell ill within 2 months of infection and displayed
      signs of neurological disease typical of IBD. In contrast, boa constrictors
      remained healthy over 2 years, despite high levels of virus throughout their
      bodies. This difference matches previous reports that pythons are more
      susceptible to IBD than boas and could reflect the possibility that boas are
      natural hosts of these viruses in the wild.

PMID- 28515292
TI  - Molluscum Contagiosum Virus MC159 Abrogates cIAP1-NEMO Interactions and Inhibits
      NEMO Polyubiquitination.
AB  - Molluscum contagiosum virus (MCV) is a dermatotropic poxvirus that causes benign
      skin lesions. MCV lesions persist because of virally encoded immune evasion
      molecules that inhibit antiviral responses. The MCV MC159 protein suppresses NF
      kappaB activation, a powerful antiviral response, via interactions with the NF
      kappaB essential modulator (NEMO) subunit of the IkappaB kinase (IKK) complex.
      Binding of MC159 to NEMO does not disrupt the IKK complex, implying that MC159
      prevents IKK activation via an as-yet-unidentified strategy. Here, we
      demonstrated that MC159 inhibited NEMO polyubiquitination, a posttranslational
      modification required for IKK and downstream NF-kappaB activation. Because MCV
      cannot be propagated in cell culture, MC159 was expressed independent of
      infection or during a surrogate vaccinia virus infection to identify how MC159
      prevented polyubiquitination. Cellular inhibitor of apoptosis protein 1 (cIAP1)
      is a cellular E3 ligase that ubiquitinates NEMO. Mutational analyses revealed
      that MC159 and cIAP1 each bind to the same NEMO region, suggesting that MC159 may
      competitively inhibit cIAP1-NEMO interactions. Indeed, MC159 prevented cIAP1-NEMO
      interactions. MC159 also diminished cIAP1-mediated NEMO polyubiquitination and
      cIAP1-induced NF-kappaB activation. These data suggest that MC159 competitively
      binds to NEMO to prevent cIAP1-induced NEMO polyubiquitination. To our knowledge,
      this is the first report of a viral protein disrupting NEMO-cIAP1 interactions to
      strategically suppress IKK activation. All viruses must antagonize antiviral
      signaling events for survival. We hypothesize that MC159 inhibits NEMO
      polyubiquitination as a clever strategy to manipulate the host cell environment
      to the benefit of the virus.IMPORTANCE Molluscum contagiosum virus (MCV) is a
      human-specific poxvirus that causes persistent skin neoplasms. The persistence of
      MCV has been attributed to viral downregulation of host cell immune responses
      such as NF-kappaB activation. We show here that the MCV MC159 protein interacts
      with the NEMO subunit of the IKK complex to prevent NEMO interactions with the
      cIAP1 E3 ubiquitin ligase. This interaction correlates with a dampening of cIAP1
      to polyubiquitinate NEMO and to activate NF-kappaB. This inhibition of cIAP1-NEMO
      interactions is a new viral strategy to minimize IKK activation and to control
      NEMO polyubiquitination. This research provides new insights into mechanisms that
      persistent viruses may use to cause long-term infection of host cells.

PMID- 28515293
TI  - Virus-Like Vesicles of Kaposi's Sarcoma-Associated Herpesvirus Activate Lytic
      Replication by Triggering Differentiation Signaling.
AB  - Virus-like vesicles (VLVs) are membrane-enclosed vesicles that resemble native
      enveloped viruses in organization but lack the viral capsid and genome. During
      the productive infection of tumor-associated gammaherpesviruses, both virions and
      VLVs are produced and are released into the extracellular space. However, studies
      of gammaherpesvirus-associated VLVs have been largely restricted by the technical
      difficulty of separating VLVs from mature virions. Here we report a strategy of
      selectively isolating VLVs by using a Kaposi's sarcoma-associated herpesvirus
      (KSHV) mutant that is defective in small capsid protein and is unable to produce
      mature virions. Using mass spectrometry analysis, we found that VLVs contained
      viral glycoproteins required for cellular entry, as well as tegument proteins
      involved in regulating lytic replication, but lacked capsid proteins. Functional
      analysis showed that VLVs induced the expression of the viral lytic activator
      RTA, initiating KSHV lytic gene expression. Furthermore, employing RNA
      sequencing, we performed a genomewide analysis of cellular responses triggered by
      VLVs and found that PRDM1, a master regulator in cell differentiation, was
      significantly upregulated. In the context of KSHV replication, we demonstrated
      that VLV-induced upregulation of PRDM1 was necessary and sufficient to reactivate
      KSHV by activating its RTA promoter. In sum, our study systematically examined
      the composition of VLVs and demonstrated their biological roles in manipulating
      host cell responses and facilitating KSHV lytic replication.IMPORTANCE Cells
      lytically infected with tumor-associated herpesviruses produce a high proportion
      of virus-like vesicles (VLVs). The composition and function of VLVs have not been
      well defined, largely due to the inability to efficiently isolate VLVs that are
      free of virions. Using a cell system capable of establishing latent KSHV
      infection and robust reactivation, we successfully isolated VLVs from a KSHV
      mutant defective in the small capsid protein. We quantitatively analyzed proteins
      and microRNAs in VLVs and characterized the roles of VLVs in manipulating host
      cells and facilitating viral infection. More importantly, we demonstrated that by
      upregulating PRDM1 expression, VLVs triggered differentiation signaling in
      targeted cells and facilitated viral lytic infection via activation of the RTA
      promoter. Our study not only demonstrates a new strategy for isolating VLVs but
      also shows the important roles of KSHV-associated VLVs in intercellular
      communication and the viral life cycle.

PMID- 28515294
TI  - Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This
      Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2.
AB  - The vaccinia virus B1 kinase is highly conserved among poxviruses and is
      essential for the viral life cycle. B1 exhibits a remarkable degree of similarity
      to vaccinia virus-related kinases (VRKs), a family of cellular kinases,
      suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1
      and VRKs have been demonstrated to target a shared substrate, the DNA binding
      protein BAF, elucidating a signaling pathway important for both mitosis and the
      antiviral response. In this study, we further characterize the role of B1 during
      vaccinia infection to gain novel insights into its regulation and integration
      with cellular signaling pathways. We begin by describing the construction and
      characterization of the first B1 deletion virus (vvDeltaB1) produced using a
      complementing cell line expressing the viral kinase. Examination of vvDeltaB1
      revealed that B1 is critical for the production of infectious virions in various
      cell types and is sufficient for BAF phosphorylation. Interestingly, the severity
      of the defect in DNA replication following the loss of B1 varied between cell
      types, leading us to posit that cellular VRKs partly complement for the absence
      of B1 in some cell lines. Using cell lines devoid of either VRK1 or VRK2, we
      tested this hypothesis and discovered that VRK2 expression facilitates DNA
      replication and allows later stages of the viral life cycle to proceed in the
      absence of B1. Finally, we present evidence that the impact of VRK2 on vaccinia
      virus is largely independent of BAF phosphorylation. These data support a model
      in which B1 and VRK2 share additional substrates important for the replication of
      cytoplasmic poxviruses.IMPORTANCE Viral mimicry of cellular signaling modulators
      provides clear evidence that the pathogen targets an important host pathway
      during infection. Poxviruses employ numerous viral homologs of cellular proteins,
      the study of which have yielded insights into signaling pathways used by both
      virus and cells alike. The vaccinia virus B1 protein is a homolog of cellular
      vaccinia virus-related kinases (VRKs) and is needed for viral DNA replication and
      likely other stages of the viral life cycle. However, much remains to be learned
      about how B1 and VRKs overlap functionally. This study utilizes new tools,
      including a B1 deletion virus and VRK knockout cells, to further characterize the
      functional links between the viral and cellular enzymes. As a result, we have
      discovered that B1 and VRK2 target a common set of substrates vital to productive
      infection of this large cytoplasmic DNA virus.

PMID- 28515295
TI  - Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.
AB  - Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV)
      strains, including many primary isolates, have been used to investigate variation
      in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART
      microRNA (miRNA) cluster 2. Determination of type 1 and type 2 EBV in saliva
      samples from people from a wide range of geographic and ethnic backgrounds
      demonstrates a small percentage of healthy white Caucasian British people
      carrying predominantly type 2 EBV. Linkage of Zp and gp350 variants to type 2 EBV
      is likely to be due to their genes being adjacent to the EBNA3 locus, which is
      one of the major determinants of the type 1/type 2 distinction. A novel
      classification of EBNA1 DNA binding domains, named QCIGP, results from phylogeny
      analysis of their protein sequences but is not linked to the type 1/type 2
      classification. The BART cluster 2 miRNA region is classified into three major
      variants through single-nucleotide polymorphisms (SNPs) in the primary miRNA
      outside the mature miRNA sequences. These SNPs can result in altered levels of
      expression of some miRNAs from the BART variant frequently present in Chinese and
      Indonesian nasopharyngeal carcinoma (NPC) samples. The EBV genetic variants
      identified here provide a basis for future, more directed analysis of association
      of specific EBV variations with EBV biology and EBV-associated
      diseases.IMPORTANCE Incidence of diseases associated with EBV varies greatly in
      different parts of the world. Thus, relationships between EBV genome sequence
      variation and health, disease, geography, and ethnicity of the host may be
      important for understanding the role of EBV in diseases and for development of an
      effective EBV vaccine. This paper provides the most comprehensive analysis so far
      of variation in specific EBV genes relevant to these diseases and proposed EBV
      vaccines. By focusing on variation in LMP1, Zp, gp350, EBNA1, and the BART miRNA
      cluster 2, new relationships with the known type 1/type 2 strains are
      demonstrated, and a novel classification of EBNA1 and the BART miRNAs is
      proposed.

PMID- 28515296
TI  - Hepatitis C Virus Lipoviroparticles Assemble in the Endoplasmic Reticulum (ER)
      and Bud off from the ER to the Golgi Compartment in COPII Vesicles.
AB  - Hepatitis C virus (HCV) exists as a lipoprotein-virus hybrid lipoviroparticle
      (LVP). In vitro studies have demonstrated the importance of apolipoproteins in
      HCV secretion and infectivity, leading to the notion that HCV coopts the
      secretion of very-low-density lipoprotein (VLDL) for its egress. However, the
      mechanisms involved in virus particle assembly and egress are still elusive. The
      biogenesis of VLDL particles occurs in the endoplasmic reticulum (ER), followed
      by subsequent lipidation in the ER and Golgi compartment. The secretion of mature
      VLDL particles occurs through the Golgi secretory pathway. HCV virions are
      believed to latch onto or fuse with the nascent VLDL particle in either the ER or
      the Golgi compartment, resulting in the generation of LVPs. In our attempt to
      unravel the collaboration between HCV and VLDL secretion, we studied HCV
      particles budding from the ER en route to the Golgi compartment in COPII
      vesicles. Biophysical characterization of COPII vesicles fractionated on an
      iodixanol gradient revealed that HCV RNA is enriched in the highly buoyant COPII
      vesicle fractions and cofractionates with apolipoprotein B (ApoB), ApoE, and the
      HCV core and envelope proteins. Electron microscopy of immunogold-labeled
      microsections revealed that the HCV envelope and core proteins colocalize with
      apolipoproteins and HCV RNA in Sec31-coated COPII vesicles. Ultrastructural
      analysis also revealed the presence of HCV structural proteins, RNA, and
      apolipoproteins in the Golgi stacks. These findings support the hypothesis that
      HCV LVPs assemble in the ER and are transported to the Golgi compartment in COPII
      vesicles to embark on the Golgi secretory route.IMPORTANCE HCV assembly and
      release accompany the formation of LVPs that circulate in the sera of HCV
      patients and are also produced in an in vitro culture system. The pathway of HCV
      morphogenesis and secretion has not been fully understood. This study
      investigates the exact site where the association of HCV virions with host
      lipoproteins occurs. Using immunoprecipitation of COPII vesicles and immunogold
      electron microscopy (EM), we characterize the existence of LVPs that
      cofractionate with lipoproteins, viral proteins, RNA, and vesicular components.
      Our results show that this assembly occurs in the ER, and LVPs thus formed are
      carried through the Golgi network by vesicular transport. This work provides a
      unique insight into the HCV LVP assembly process within infected cells and offers
      opportunities for designing antiviral therapeutic cellular targets.

PMID- 28515297
TI  - Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase
      Fidelity.
AB  - Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol)
      catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of
      proofreading activity allow FMDV to rapidly mutate and adapt to dynamic
      environments. In this study, we used the structure of FMDV 3Dpol in combination
      with previously reported results from similar picornaviral polymerases to design
      point mutations that would alter replication fidelity. In particular, we targeted
      Trp237 within conserved polymerase motif A because of the low reversion potential
      inherent in the single UGG codon. Using biochemical and genetic tools, we show
      that the replacement of tryptophan 237 with phenylalanine imparts higher
      fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity
      phenotypes. Viruses containing these W237 substitutions show in vitro growth
      kinetics and plaque morphologies similar to those of the wild-type (WT) A24
      Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained
      fitness during coinfection with the wild-type virus. The higher-fidelity W237F
      (W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs
      ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I
      (W237ILF) and W237LLF mutant viruses exhibited lower ribavirin resistance.
      Interestingly, the variant viruses showed heterogeneous and slightly delayed
      growth kinetics in primary porcine kidney cells, and they were significantly
      attenuated in mouse infection experiments. These data demonstrate, for a single
      virus, that either increased or decreased RdRp fidelity attenuates virus growth
      in animals, which is a desirable feature for the development of safer and
      genetically more stable vaccine candidates.IMPORTANCE Foot-and-mouth disease
      (FMD) is the most devastating disease affecting livestock worldwide. Here, using
      structural and biochemical analyses, we have identified FMDV 3Dpol mutations that
      affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3Dpol
      tryptophan residue 237 were genetically stable and displayed plaque phenotypes
      and growth kinetics similar to those of the wild-type virus in cell culture. We
      further demonstrate that viruses harboring either a W237FHF substitution or
      W237ILF and W237LLF mutations were highly attenuated in animals. Our study shows
      that obtaining 3Dpol fidelity variants by protein engineering based on polymerase
      structure and function could be exploited for the development of attenuated FMDV
      vaccine candidates that are safer and more stable than strains obtained by
      selective pressure via mutagenic nucleotides or adaptation approaches.

PMID- 28515298
TI  - Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA
      Translation.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the
      Bunyaviridae family, causing severe illness with high mortality rates in humans.
      Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA
      translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with
      high affinity. It facilitates the translation of reporter mRNA both in vivo and
      in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors
      the translation of both capped and uncapped mRNAs, demonstrating the independence
      of this translation strategy on the 5' cap. Unlike the canonical host translation
      machinery, inhibition of eIF4F complex, an amalgam of three initiation factors,
      eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the
      CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of
      eIF4G alone by the human rhinovirus 2A protease abrogated this translation
      strategy. Our results demonstrate that eIF4F complex formation is not required
      but eIF4G plays a critical role in this translation mechanism. Our results
      suggest that CCHFV has adopted a unique translation mechanism to facilitate the
      translation of viral mRNAs in the host cell cytoplasm where cellular transcripts
      are competing for the same translation apparatus.IMPORTANCE Crimean-Congo
      hemorrhagic fever, a highly contagious viral disease endemic to more than 30
      countries, has limited treatment options. Our results demonstrate that NP favors
      the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly
      likely that CCHFV uses an NP-mediated translation strategy for the rapid
      synthesis of viral proteins during the course of infection. Shutdown of this
      translation mechanism might selectively impact viral protein synthesis,
      suggesting that an NP-mediated translation strategy is a target for therapeutic
      intervention against this viral disease.

PMID- 28515299
TI  - A Diverse Range of Novel RNA Viruses in Geographically Distinct Honey Bee
      Populations.
AB  - Understanding the diversity and consequences of viruses present in honey bees is
      critical for maintaining pollinator health and managing the spread of disease.
      The viral landscape of honey bees (Apis mellifera) has changed dramatically since
      the emergence of the parasitic mite Varroa destructor, which increased the spread
      of virulent variants of viruses such as deformed wing virus. Previous genomic
      studies have focused on colonies suffering from infections by Varroa and virulent
      viruses, which could mask other viral species present in honey bees, resulting in
      a distorted view of viral diversity. To capture the viral diversity within
      colonies that are exposed to mites but do not suffer the ultimate consequences of
      the infestation, we examined populations of honey bees that have evolved
      naturally or have been selected for resistance to Varroa This analysis revealed
      seven novel viruses isolated from honey bees sampled globally, including the
      first identification of negative-sense RNA viruses in honey bees. Notably, two
      rhabdoviruses were present in three geographically diverse locations and were
      also present in Varroa mites parasitizing the bees. To characterize the antiviral
      response, we performed deep sequencing of small RNA populations in honey bees and
      mites. This provided evidence of a Dicer-mediated immune response in honey bees,
      while the viral small RNA profile in Varroa mites was novel and distinct from the
      response observed in bees. Overall, we show that viral diversity in honey bee
      colonies is greater than previously thought, which encourages additional studies
      of the bee virome on a global scale and which may ultimately improve disease
      management.IMPORTANCE Honey bee populations have become increasingly susceptible
      to colony losses due to pathogenic viruses spread by parasitic Varroa mites. To
      date, 24 viruses have been described in honey bees, with most belonging to the
      order Picornavirales Collapsing Varroa-infected colonies are often overwhelmed
      with high levels of picornaviruses. To examine the underlying viral diversity in
      honey bees, we employed viral metatranscriptomics analyses on three
      geographically diverse Varroa-resistant populations from Europe, Africa, and the
      Pacific. We describe seven novel viruses from a range of diverse viral families,
      including two viruses that are present in all three locations. In honey bees,
      small RNA sequences indicate that these viruses are processed by Dicer and the
      RNA interference pathway, whereas Varroa mites produce strikingly novel small RNA
      patterns. This work increases the number and diversity of known honey bee viruses
      and will ultimately contribute to improved disease management in our most
      important agricultural pollinator.

PMID- 28515300
TI  - A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a
      New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the
      Ferret Model.
AB  - In December 2016, a low-pathogenic avian influenza (LPAI) A(H7N2) virus was
      identified to be the causative source of an outbreak in a cat shelter in New York
      City, which subsequently spread to multiple shelters in the states of New York
      and Pennsylvania. One person with occupational exposure to infected cats became
      infected with the virus, representing the first LPAI H7N2 virus infection in a
      human in North America since 2003. Considering the close contact that frequently
      occurs between companion animals and humans, it was critical to assess the
      relative risk of this novel virus to public health. The virus isolated from the
      human case, A/New York/108/2016 (NY/108), caused mild and transient illness in
      ferrets and mice but did not transmit to naive cohoused ferrets following
      traditional or aerosol-based inoculation methods. The environmental persistence
      of NY/108 virus was generally comparable to that of other LPAI H7N2 viruses.
      However, NY/108 virus replicated in human bronchial epithelial cells with an
      increased efficiency compared with that of previously isolated H7N2 viruses.
      Furthermore, the novel H7N2 virus was found to utilize a relatively lower pH for
      hemagglutinin activation, similar to human influenza viruses. Our data suggest
      that the LPAI H7N2 virus requires further adaptation before representing a
      substantial threat to public health. However, the reemergence of an LPAI H7N2
      virus in the northeastern United States underscores the need for continuous
      surveillance of emerging zoonotic influenza viruses inclusive of mammalian
      species, such as domestic felines, that are not commonly considered intermediate
      hosts for avian influenza viruses.IMPORTANCE Avian influenza viruses are capable
      of crossing the species barrier to infect mammals, an event of public health
      concern due to the potential acquisition of a pandemic phenotype. In December
      2016, an H7N2 virus caused an outbreak in cats in multiple animal shelters in New
      York State. This was the first detection of this virus in the northeastern United
      States in over a decade and the first documented infection of a felid with an
      H7N2 virus. A veterinarian became infected following occupational exposure to
      H7N2 virus-infected cats, necessitating the evaluation of this virus for its
      capacity to cause disease in mammals. While the H7N2 virus was associated with
      mild illness in mice and ferrets and did not spread well between ferrets, it
      nonetheless possessed several markers of virulence for mammals. These data
      highlight the promiscuity of influenza viruses and the need for diligent
      surveillance across multiple species to quickly identify an emerging strain with
      pandemic potential.

PMID- 28515301
TI  - Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced
      Viral M1 mRNA.
AB  - Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase
      in the cell nucleus before being exported to the cytoplasm for translation.
      Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1
      matrix protein and a spliced transcript that encodes the M2 ion channel. Export
      of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear
      how they are recruited to the export machinery or how the intron-containing but
      unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using
      fluorescent in situ hybridization to monitor segment 7 mRNA localization, we
      found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the
      absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid
      transfection and in mutant virus-infected cells. This effect was independent of
      any major effect on steady-state levels of segment 7 mRNA or splicing but
      corresponded to a ~5-fold reduction in the accumulation of M1. A similar defect
      in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant
      virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain
      and effector domain. Furthermore, while wild-type NS1 interacted with cellular
      NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1
      polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1
      facilitates late viral gene expression by acting as an adaptor between viral
      mRNAs and the cellular nuclear export machinery to promote their nuclear
      export.IMPORTANCE Influenza A virus is a major pathogen of a wide variety of
      mammalian and avian species that threatens public health and food security. A
      fuller understanding of the virus life cycle is important to aid control
      strategies. The virus has a small genome that encodes relatively few proteins
      that are often multifunctional. Here, we characterize a new function for the NS1
      protein, showing that, as well as previously identified roles in antagonizing the
      innate immune defenses of the cell and directly upregulating translation of viral
      mRNAs, it also promotes the nuclear export of the viral late gene mRNAs by acting
      as an adaptor between the viral mRNAs and the cellular mRNA nuclear export
      machinery.

PMID- 28515302
TI  - Transposon Mutagenesis of the Zika Virus Genome Highlights Regions Essential for
      RNA Replication and Restricted for Immune Evasion.
AB  - The molecular constraints affecting Zika virus (ZIKV) evolution are not well
      understood. To investigate ZIKV genetic flexibility, we used transposon
      mutagenesis to add 15-nucleotide insertions throughout the ZIKV MR766 genome and
      subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants
      replicated, which likely reflects a high degree of functional constraints on the
      genome. The NS1 gene exhibited distinct mutational tolerances at different stages
      of the screen. This result may define regions of the NS1 protein that are
      required for the different stages of the viral life cycle. The ZIKV structural
      genes showed the highest degree of insertional tolerance. Although the envelope
      (E) protein exhibited particular flexibility, the highly conserved envelope
      domain II (EDII) fusion loop of the E protein was intolerant of transposon
      insertions. The fusion loop is also a target of pan-flavivirus antibodies that
      are generated against other flaviviruses and neutralize a broad range of dengue
      virus and ZIKV isolates. The genetic restrictions identified within the epitopes
      in the EDII fusion loop likely explain the sequence and antigenic conservation of
      these regions in ZIKV and among multiple flaviviruses. Thus, our results provide
      insights into the genetic restrictions on ZIKV that may affect the evolution of
      this virus.IMPORTANCE Zika virus recently emerged as a significant human
      pathogen. Determining the genetic constraints on Zika virus is important for
      understanding the factors affecting viral evolution. We used a genome-wide
      transposon mutagenesis screen to identify where mutations were tolerated in
      replicating viruses. We found that the genetic regions involved in RNA
      replication were mostly intolerant of mutations. The genes coding for structural
      proteins were more permissive to mutations. Despite the flexibility observed in
      these regions, we found that epitopes bound by broadly reactive antibodies were
      genetically constrained. This finding may explain the genetic conservation of
      these epitopes among flaviviruses.

PMID- 28515306
TI  - Intermediate-Term Memory as a Bridge between Working and Long-Term Memory.

PMID- 28515304
TI  - Reactive Oxygen Species-Mediated c-Jun NH2-Terminal Kinase Activation Contributes
      to Hepatitis B Virus X Protein-Induced Autophagy via Regulation of the Beclin
      1/Bcl-2 Interaction.
AB  - Autophagy is closely associated with the regulation of hepatitis B virus (HBV)
      replication. HBV X protein (HBx), a multifunctional regulator in HBV-associated
      biological processes, has been demonstrated to be crucial for autophagy induction
      by HBV. However, the molecular mechanisms of autophagy induction by HBx,
      especially the signaling pathways involved, remain elusive. In the present
      investigation, we demonstrated that HBx induced autophagosome formation
      independently of the class I phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR
      signaling pathway. In contrast, the class III PI3K(VPS34)/beclin-1 pathway was
      revealed to be critical for HBx-induced autophagosome formation. Further study
      showed that HBx did not affect the level of VPS34 and beclin-1 expression but
      inhibited beclin-1/Bcl-2 association, and c-Jun NH2-terminal kinase (JNK)
      signaling was found to be important for this process. Moreover, it was found that
      HBx treatment led to the generation of reactive oxygen species (ROS), and
      inhibition of ROS activity abrogated both JNK activation and autophagosome
      formation. Of importance, ROS-JNK signaling was also revealed to play an
      important role in HBV-induced autophagosome formation and subsequent HBV
      replication. These data may provide deeper insight into the mechanisms of
      autophagy induction by HBx and help in the design of new therapeutic strategies
      against HBV infection.IMPORTANCE HBx plays a key role in diverse HBV-associated
      biological processes, including autophagy induction. However, the molecular
      mechanisms of autophagy induction by HBx, especially the signaling pathways
      involved, remain elusive. In the present investigation, we found that HBx induced
      autophagy independently of the class I PI3K/AKT/mTOR signaling pathway, while the
      class III PI3K(VPS34)/beclin-1 pathway was revealed to be crucial for this
      process. Further data showed that ROS-JNK activation by HBx resulted in the
      release of beclin-1 from its association with Bcl-2 to form a complex with VPS34,
      thus enhancing autophagosome formation. Of importance, ROS-JNK signaling was also
      demonstrated to be critical for HBV replication via regulation of autophagy
      induction. These data help to elucidate the molecular mechanisms of autophagy
      induction by HBx/HBV and might be useful for designing novel therapeutic
      approaches to HBV infection.

PMID- 28515303
TI  - Spontaneous and Vaccine-Induced Clearance of Mus Musculus Papillomavirus 1
      Infection.
AB  - Mus musculus papillomavirus 1 (MmuPV1/MusPV1) induces persistent papillomas in
      immunodeficient mice but not in common laboratory strains. To facilitate the
      study of immune control, we sought an outbred and immunocompetent laboratory
      mouse strain in which persistent papillomas could be established. We found that
      challenge of SKH1 mice (Crl:SKH1-Hrhr) with MmuPV1 by scarification on their tail
      resulted in three clinical outcomes: (i) persistent (>2-month) papillomas (~20%);
      (ii) transient papillomas that spontaneously regress, typically within 2 months
      (~15%); and (iii) no visible papillomas and viral clearance (~65%). SKH1 mice
      with persistent papillomas were treated by using a candidate
      preventive/therapeutic naked-DNA vaccine that expresses human calreticulin (hCRT)
      fused in frame to MmuPV1 E6 (mE6) and mE7 early proteins and residues 11 to 200
      of the late protein L2 (hCRTmE6/mE7/mL2). Three intramuscular DNA vaccinations
      were delivered biweekly via in vivo electroporation, and both humoral and CD8 T
      cell responses were mapped and measured. Previously persistent papillomas
      disappeared within 2 months after the final vaccination. Coincident virologic
      clearance was confirmed by in situ hybridization and a failure of disease to
      recur after CD3 T cell depletion. Vaccination induced strong mE6 and mE7 CD8+ T
      cell responses in all mice, although they were significantly weaker in mice that
      initially presented with persistent warts than in those that spontaneously
      cleared their infection. A human papillomavirus 16 (HPV16)-targeted version of
      the DNA vaccine also induced L2 antibodies and protected mice from vaginal
      challenge with an HPV16 pseudovirus. Thus, MmuPV1 challenge of SKH1 mice is a
      promising model of spontaneous and immunotherapy-directed clearances of HPV
      related disease.IMPORTANCE High-risk-type human papillomaviruses (hrHPVs) cause
      5% of all cancer cases worldwide, notably cervical, anogenital, and oropharyngeal
      cancers. Since preventative HPV vaccines have not been widely used in many
      countries and do not impact existing infections, there is considerable interest
      in the development of therapeutic vaccines to address existing disease and
      infections. The strict tropism of HPV requires the use of animal papillomavirus
      models for therapeutic vaccine development. However, MmuPV1 failed to grow in
      common laboratory strains of mice with an intact immune system. We show that
      MmuPV1 challenge of the outbred immunocompetent SKH1 strain produces both
      transient and persistent papillomas and that vaccination of the mice with a DNA
      expressing an MmuPV1 E6E7L2 fusion with calreticulin can rapidly clear persistent
      papillomas. Furthermore, an HPV16-targeted version of the DNA can protect against
      vaginal challenge with HPV16, suggesting the promise of this approach to both
      prevent and treat papillomavirus-related disease.

PMID- 28515307
TI  - Action Organization in Lateral Occipitotemporal Cortex.

PMID- 28515305
TI  - Cell Cycle-Dependent Expression of Adeno-Associated Virus 2 (AAV2) Rep in
      Coinfections with Herpes Simplex Virus 1 (HSV-1) Gives Rise to a Mosaic of Cells
      Replicating either AAV2 or HSV-1.
AB  - Adeno-associated virus 2 (AAV2) depends on the simultaneous presence of a helper
      virus such as herpes simplex virus 1 (HSV-1) for productive replication. At the
      same time, AAV2 efficiently blocks the replication of HSV-1, which would
      eventually limit its own replication by diminishing the helper virus reservoir.
      This discrepancy begs the question of how AAV2 and HSV-1 can coexist in a cell
      population. Here we show that in coinfected cultures, AAV2 DNA replication takes
      place almost exclusively in S/G2-phase cells, while HSV-1 DNA replication is
      restricted to G1 phase. Live microscopy revealed that not only wild-type AAV2
      (wtAAV2) replication but also reporter gene expression from both single-stranded
      and double-stranded (self-complementary) recombinant AAV2 vectors preferentially
      occurs in S/G2-phase cells, suggesting that the preference for S/G2 phase is
      independent of the nature of the viral genome. Interestingly, however, a
      substantial proportion of S/G2-phase cells transduced by the double-stranded but
      not the single-stranded recombinant AAV2 vectors progressed through mitosis in
      the absence of the helper virus. We conclude that cell cycle-dependent AAV2 rep
      expression facilitates cell cycle-dependent AAV2 DNA replication and inhibits HSV
      1 DNA replication. This may limit competition for cellular and viral helper
      factors and, hence, creates a biological niche for either virus to
      replicate.IMPORTANCE Adeno-associated virus 2 (AAV2) differs from most other
      viruses, as it requires not only a host cell for replication but also a helper
      virus such as an adenovirus or a herpesvirus. This situation inevitably leads to
      competition for cellular resources. AAV2 has been shown to efficiently inhibit
      the replication of helper viruses. Here we present a new facet of the interaction
      between AAV2 and one of its helper viruses, herpes simplex virus 1 (HSV-1). We
      observed that AAV2 rep gene expression is cell cycle dependent and gives rise to
      distinct time-controlled windows for HSV-1 replication. High Rep protein levels
      in S/G2 phase support AAV2 replication and inhibit HSV-1 replication. Conversely,
      low Rep protein levels in G1 phase permit HSV-1 replication but are insufficient
      for AAV2 replication. This allows both viruses to productively replicate in
      distinct sets of dividing cells.

PMID- 28515311
TI  - Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N
      end rule pathway.
AB  - We found that the heat shock protein 90 (Hsp90) chaperone system of the yeast
      Saccharomyces cerevisiae is greatly impaired in naa10Delta cells, which lack the
      NatA Nalpha-terminal acetylase (Nt-acetylase) and therefore cannot N-terminally
      acetylate a majority of normally N-terminally acetylated proteins, including
      Hsp90 and most of its cochaperones. Chk1, a mitotic checkpoint kinase and a
      client of Hsp90, was degraded relatively slowly in wild-type cells but was
      rapidly destroyed in naa10Delta cells by the Arg/N-end rule pathway, which
      recognized a C terminus-proximal degron of Chk1. Diverse proteins (in addition to
      Chk1) that are shown here to be targeted for degradation by the Arg/N-end rule
      pathway in naa10Delta cells include Kar4, Tup1, Gpd1, Ste11, and also,
      remarkably, the main Hsp90 chaperone (Hsc82) itself. Protection of Chk1 by Hsp90
      could be overridden not only by ablation of the NatA Nt-acetylase but also by
      overexpression of the Arg/N-end rule pathway in wild-type cells. Split ubiquitin
      binding assays detected interactions between Hsp90 and Chk1 in wild-type cells
      but not in naa10Delta cells. These and related results revealed a major role of
      Nt-acetylation in the Hsp90-mediated protein homeostasis, a strong up-regulation
      of the Arg/N-end rule pathway in the absence of NatA, and showed that a number of
      Hsp90 clients are previously unknown substrates of the Arg/N-end rule pathway.

PMID- 28515313
TI  - Low temperature nullifies the circadian clock in cyanobacteria through Hopf
      bifurcation.
AB  - Cold temperatures lead to nullification of circadian rhythms in many organisms.
      Two typical scenarios explain the disappearance of rhythmicity: the first is
      oscillation death, which is the transition from self-sustained oscillation to
      damped oscillation that occurs at a critical temperature. The second scenario is
      oscillation arrest, in which oscillation terminates at a certain phase. In the
      field of nonlinear dynamics, these mechanisms are called the Hopf bifurcation and
      the saddle-node on an invariant circle bifurcation, respectively. Although these
      mechanisms lead to distinct dynamical properties near the critical temperature,
      it is unclear to which scenario the circadian clock belongs. Here we reduced the
      temperature to dampen the reconstituted circadian rhythm of phosphorylation of
      the recombinant cyanobacterial clock protein KaiC. The data led us to conclude
      that Hopf bifurcation occurred at ~19  degrees C. Below this critical
      temperature, the self-sustained rhythms of KaiC phosphorylation transformed to
      damped oscillations, which are predicted by the Hopf bifurcation theory.
      Moreover, we detected resonant oscillations below the critical temperature when
      temperature was periodically varied, which was reproduced by numerical
      simulations. Our findings suggest that the transition to a damped oscillation
      through Hopf bifurcation contributes to maintaining the circadian rhythm of
      cyanobacteria through resonance at cold temperatures.

PMID- 28515312
TI  - Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to
      maintain endurance capacity.
AB  - Brain glycogen stored in astrocytes provides lactate as an energy source to
      neurons through monocarboxylate transporters (MCTs) to maintain neuronal
      functions such as hippocampus-regulated memory formation. Although prolonged
      exhaustive exercise decreases brain glycogen, the role of this decrease and
      lactate transport in the exercising brain remains less clear. Because muscle
      glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays
      an energetic role in the prolonged-exercising brain to maintain endurance
      capacity through lactate transport. To test this hypothesis, we used a rat model
      of exhaustive exercise and capillary electrophoresis-mass spectrometry-based
      metabolomics to observe comprehensive energetics of the brain (cortex and
      hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted
      but brain glycogen was only decreased. The levels of MCT2, which takes up lactate
      in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed
      that brain, but not muscle, ATP was maintained with lactate and other
      glycogenolytic/glycolytic sources. Intracerebroventricular injection of the
      glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not
      affect peripheral glycemic conditions but suppressed brain lactate production and
      decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, alpha-cyano-4
      hydroxy-cinnamate, triggered a similar response that resulted in lower endurance
      capacity. These findings provide direct evidence for the energetic role of
      astrocytic glycogen-derived lactate in the exhaustive-exercising brain,
      implicating the significance of brain glycogen level in endurance capacity.
      Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons
      in the exhausted brain.

PMID- 28515314
TI  - The mzIdentML Data Standard Version 1.2, Supporting Advances in Proteome
      Informatics.
AB  - The first stable version of the Proteomics Standards Initiative mzIdentML open
      data standard (version 1.1) was published in 2012-capturing the outputs of
      peptide and protein identification software. In the intervening years, the
      standard has become well-supported in both commercial and open software, as well
      as a submission and download format for public repositories. Here we report a new
      release of mzIdentML (version 1.2) that is required to keep pace with emerging
      practice in proteome informatics. New features have been added to support: (1)
      scores associated with localization of modifications on peptides; (2) statistics
      performed at the level of peptides; (3) identification of cross-linked peptides;
      and (4) support for proteogenomics approaches. In addition, there is now improved
      support for the encoding of de novo sequencing of peptides, spectral library
      searches, and protein inference. As a key point, the underlying XML schema has
      only undergone very minor modifications to simplify as much as possible the
      transition from version 1.1 to version 1.2 for implementers, but there have been
      several notable updates to the format specification, implementation guidelines,
      controlled vocabularies and validation software. mzIdentML 1.2 can be described
      as backwards compatible, in that reading software designed for mzIdentML 1.1
      should function in most cases without adaptation. We anticipate that these
      developments will provide a continued stable base for software teams working to
      implement the standard. All the related documentation is accessible at
      http://www.psidev.info/mzidentml.

PMID- 28515315
TI  - The C-terminal peptide of Aquifex aeolicus riboflavin synthase directs
      encapsulation of native and foreign guests by a cage-forming lumazine synthase.
AB  - Encapsulation of specific enzymes in self-assembling protein cages is a hallmark
      of bacterial compartments that function as counterparts to eukaryotic organelles.
      The cage-forming enzyme lumazine synthase (LS) from Bacillus subtilis (BsLS), for
      example, encapsulates riboflavin synthase (BsRS), enabling channeling of lumazine
      from the site of its generation to the site of its conversion to vitamin B2
      Elucidating the molecular mechanisms underlying the assembly of these
      supramolecular complexes could help inform new approaches for metabolic
      engineering, nanotechnology, and drug delivery. To that end, we investigated a
      thermostable LS from Aquifex aeolicus (AaLS) and found that it also forms cage
      complexes with the cognate riboflavin synthase (AaRS) when both proteins are co
      produced in the cytosol of Escherichia coli A 12-amino acid-long peptide at the C
      terminus of AaRS serves as a specific localization sequence responsible for
      targeting the guest to the protein compartment. Sequence comparisons suggested
      that analogous peptide segments likely direct RS complexation by LS cages in
      other bacterial species. Covalent fusion of this peptide tag to heterologous
      guest molecules led to their internalization into AaLS assemblies both in vivo
      and in vitro, providing a firm foundation for creating tailored biomimetic
      nanocompartments for medical and biotechnological applications.

PMID- 28515317
TI  - Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds
      critical insight into host lipid utilization by M. tuberculosis.
AB  - Mycobacterium tuberculosis causes tuberculosis in humans and predominantly
      infects alveolar macrophages. To survive inside host lesions and to evade immune
      surveillance, this pathogen has developed many strategies. For example, M.
      tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged
      persistence within hypoxic host microenvironments. M. tuberculosis imports these
      metabolites through its respective transporters, and in the case of host fatty
      acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for
      cleavage of fatty acids from host lipids? We show herein that a previously
      uncharacterized membrane-associated M. tuberculosis protein encoded by Rv2672 is
      conserved exclusively in actinomycetes, exhibits both lipase and protease
      activities, is secreted into macrophages, and catalyzes host lipid hydrolysis. In
      light of these functions, we annotated Rv2672 as mycobacterial secreted hydrolase
      1 (Msh1). Furthermore, we found that this enzyme is up-regulated both in an in
      vitro model of hypoxic stress and in a mouse model of M. tuberculosis infection,
      suggesting that the pathogen requires Msh1 under hypoxic conditions. Silencing
      Msh1 expression compromised the ability of M. tuberculosis to proliferate inside
      lipid-rich foamy macrophages but not under regular culture conditions in vitro,
      underscoring Msh1's importance for M. tuberculosis persistence in lipid-rich
      microenvironments. Of note, this is the first report providing insight into the
      mechanism of host lipid catabolism by an M. tuberculosis enzyme, augmenting our
      current understanding of how M. tuberculosis meets its nutrient requirements
      under hypoxic conditions.

PMID- 28515316
TI  - DNA-damage-induced degradation of EXO1 exonuclease limits DNA end resection to
      ensure accurate DNA repair.
AB  - End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded
      DNA facilitates DSB repair via error-free homologous recombination (HR) while
      stymieing repair by the error-prone non-homologous end joining (NHEJ) pathway.
      Activation of DNA end resection involves phosphorylation of the 5' to 3'
      exonuclease EXO1 by the phosphoinositide 3-kinase-like kinases ATM (ataxia
      telangiectasia-mutated) and ATR (ATM and Rad3-related) and by the cyclin
      dependent kinases 1 and 2. After activation, EXO1 must also be restrained to
      prevent over-resection that is known to hamper optimal HR and trigger global
      genomic instability. However, mechanisms by which EXO1 is restrained are still
      unclear. Here, we report that EXO1 is rapidly degraded by the ubiquitin
      proteasome system soon after DSB induction in human cells. ATR inhibition
      attenuated DNA-damage-induced EXO1 degradation, indicating that ATR-mediated
      phosphorylation of EXO1 targets it for degradation. In accord with these results,
      EXO1 became resistant to degradation when its SQ motifs required for ATR-mediated
      phosphorylation were mutated. We show that upon the induction of DNA damage, EXO1
      is ubiquitinated by a member of the Skp1-Cullin1-F-box (SCF) family of ubiquitin
      ligases in a phosphorylation-dependent manner. Importantly, expression of
      degradation-resistant EXO1 resulted in hyper-resection, which attenuated both
      NHEJ and HR and severely compromised DSB repair resulting in chromosomal
      instability. These findings indicate that the coupling of EXO1 activation with
      its eventual degradation is a timing mechanism that limits the extent of DNA end
      resection for accurate DNA repair.

PMID- 28515318
TI  - Molecular mechanism of activation of class IA phosphoinositide 3-kinases (PI3Ks)
      by membrane-localized HRas.
AB  - Class IA PI3Ks are involved in the generation of the key lipid signaling molecule
      phosphatidylinositol 3,4,5-trisphosphate (PIP3), and inappropriate activation of
      this pathway is implicated in a multitude of human diseases, including cancer,
      inflammation, and primary immunodeficiencies. Class IA PI3Ks are activated
      downstream of the Ras superfamily of GTPases, and Ras-PI3K interaction plays a
      key role in promoting tumor formation and maintenance in Ras-driven tumors.
      Investigating the detailed molecular events in the Ras-PI3K interaction has been
      challenging because it occurs on a membrane surface. Here, using maleimide
      functionalized lipid vesicles, we successfully generated membrane-resident HRas
      and evaluated its effect on PI3K signaling in lipid kinase assays and through
      analysis with hydrogen-deuterium exchange MS. We screened all class IA PI3K
      isoforms and found that HRas activates both p110alpha and p110delta isoforms but
      does not activate p110beta. The p110alpha and p110delta activation by Ras was
      synergistic with activation by a soluble phosphopeptide derived from receptor
      tyrosine kinases. Hydrogen-deuterium exchange MS revealed that membrane-resident
      HRas, but not soluble HRas, enhances conformational changes associated with
      membrane binding by increasing membrane recruitment of both p110alpha and
      p110delta. Together, these results afford detailed molecular insight into the Ras
      PI3K signaling complex, provide a framework for screening Ras inhibitors, and
      shed light on the isoform specificity of Ras-PI3K interactions in a native
      membrane context.

PMID- 28515319
TI  - The h-region of twin-arginine signal peptides supports productive binding of
      bacterial Tat precursor proteins to the TatBC receptor complex.
AB  - The twin-arginine translocation (Tat) pathway transports folded proteins across
      bacterial membranes. Tat precursor proteins possess a conserved twin-arginine
      (RR) motif in their signal peptides that is involved in their binding to the Tat
      translocase, but some facets of this interaction remain unclear. Here, we
      investigated the role of the hydrophobic (h-) region of the Escherichia coli
      trimethylamine N-oxide reductase (TorA) signal peptide in TatBC receptor binding
      in vivo and in vitro We show that besides the RR motif, a minimal, functional h
      region in the signal peptide is required for Tat-dependent export in Escherichia
      coli Furthermore, we identified mutations in the h-region that synergistically
      suppressed the export defect of a TorA[KQ]-30aa-MalE Tat reporter protein in
      which the RR motif was replaced with a lysine-glutamine pair. Strikingly, all
      suppressor mutations increased the hydrophobicity of the h-region. By
      systematically replacing a neutral residue in the h-region with various amino
      acids, we detected a positive correlation between the hydrophobicity of the h
      region and the translocation efficiency of the resulting reporter variants. In
      vitro cross-linking of residues located in the periplasmically-oriented part of
      the TatBC receptor to TorA[KQ]-30aa-MalE reporter variants harboring a more
      hydrophobic h-region in their signal peptides confirmed that unlike in TorA[KQ]
      30aa-MalE with an unaltered h-region, the mutated reporters moved deep into the
      TatBC-binding cavity. Our results clearly indicate that, besides the Tat motif,
      the h-region of the Tat signal peptides is another important binding determinant
      that significantly contributes to the productive interaction of Tat precursor
      proteins with the TatBC receptor complex.

PMID- 28515320
TI  - Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin
      and ITIM domain (TIGIT).
AB  - T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed
      on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin
      like adhesion molecules and thus plays a critical role in the innate immune
      response to malignant transformation. Although the TIGIT nectin-like protein-5
      (necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor
      that is broadly over-expressed in breast and ovarian cancer, remains unknown.
      Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is
      most distal from the membrane with an affinity of 6 MUm, which was moderately
      lower than the affinity observed for the TIGIT/necl-5 interaction (3.2 MUm). The
      TIGIT/nectin-2 binding disrupted pre-assembled nectin-2 oligomers, suggesting
      that receptor-ligand and ligand-ligand associations are mutually exclusive
      events. Indeed, the crystal structure of TIGIT bound to the first immunoglobulin
      domain of nectin-2 indicated that the receptor and ligand dock using the same
      molecular surface and a conserved "lock and key" binding motifs previously
      observed to mediate nectin/nectin homotypic interactions as well as TIGIT/necl-5
      recognition. Using a mutagenesis approach, we dissected the energetic basis for
      the TIGIT/nectin-2 interaction and revealed that an "aromatic key" of nectin-2 is
      critical for this interaction, whereas variations in the lock were tolerated.
      Moreover, we found that the C-C' loop of the ligand dictates the TIGIT binding
      hierarchy. Altogether, these findings broaden our understanding of nectin/nectin
      receptor interactions and have implications for better understanding the
      molecular basis for autoimmune disease and cancer.

PMID- 28515321
TI  - Flavin-containing monooxygenases in aging and disease: Emerging roles for ancient
      enzymes.
AB  - Flavin-containing monooxygenases (FMOs) are primarily studied as xenobiotic
      metabolizing enzymes with a prominent role in drug metabolism. In contrast,
      endogenous functions and substrates of FMOs are less well understood. A growing
      body of recent evidence, however, implicates FMOs in aging, several diseases, and
      metabolic pathways. The evidence suggests an important role for these well
      conserved proteins in multiple processes and raises questions about the
      endogenous substrate(s) and regulation of FMOs. Here, we present an overview of
      evidence for FMOs' involvement in aging and disease, discussing the biological
      context and arguing for increased investigation into the function of these
      enzymes.

PMID- 28515322
TI  - Gbetagamma directly modulates vesicle fusion by competing with synaptotagmin for
      binding to neuronal SNARE proteins embedded in membranes.
AB  - Gi/o-coupled G protein-coupled receptors can inhibit neurotransmitter release at
      synapses via multiple mechanisms. In addition to Gbetagamma-mediated modulation
      of voltage-gated calcium channels (VGCC), inhibition can also be mediated through
      the direct interaction of Gbetagamma subunits with the soluble N-ethylmaleimide
      attachment protein receptor (SNARE) complex of the vesicle fusion apparatus.
      Binding studies with soluble SNARE complexes have shown that Gbetagamma binds to
      both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs,
      competing with synaptotagmin 1(syt1) for binding sites on t-SNARE. However, in
      secretory cells, Gbetagamma, SNAREs, and synaptotagmin interact in the lipid
      environment of a vesicle at the plasma membrane. To approximate this environment,
      we show that fluorescently labeled Gbetagamma interacts specifically with lipid
      embedded t-SNAREs consisting of full-length syntaxin 1 and SNAP-25B at the
      membrane, as measured by fluorescence polarization. Fluorescently labeled syt1
      undergoes competition with Gbetagamma for SNARE-binding sites in lipid
      environments. Mutant Gbetagamma subunits that were previously shown to be more
      efficacious at inhibiting Ca2+-triggered exocytotic release than wild-type
      Gbetagamma were also shown to bind SNAREs at a higher affinity than wild type in
      a lipid environment. These mutant Gbetagamma subunits were unable to inhibit VGCC
      currents. Specific peptides corresponding to regions on Gbeta and Ggamma shown to
      be important for the interaction disrupt the interaction in a concentration
      dependent manner. In in vitro fusion assays using full-length t- and v-SNAREs
      embedded in liposomes, Gbetagamma inhibited Ca2+/synaptotagmin-dependent fusion.
      Together, these studies demonstrate the importance of these regions for the
      Gbetagamma-SNARE interaction and show that the target of Gbetagamma, downstream
      of VGCC, is the membrane-embedded SNARE complex.

PMID- 28515324
TI  - The diferric-tyrosyl radical cluster of ribonucleotide reductase and cytosolic
      iron-sulfur clusters have distinct and similar biogenesis requirements.
AB  - How each metalloprotein assembles the correct metal at the proper binding site
      presents challenges to the cell. The di-iron enzyme ribonucleotide reductase
      (RNR) uses a diferric-tyrosyl radical (FeIII2-Y*) cofactor to initiate nucleotide
      reduction. Assembly of this cofactor requires O2, FeII, and a reducing
      equivalent. Recent studies show that RNR cofactor biosynthesis shares the same
      source of iron, in the form of [2Fe-2S]-GSH2 from the monothiol glutaredoxin
      Grx3/4, and the same electron source, in the form of the Dre2-Tah18 electron
      transfer chain, with the cytosolic iron-sulfur protein assembly (CIA) machinery
      required for maturation of [4Fe-4S] clusters in cytosolic and nuclear proteins.
      Here, we further investigated the interplay between the formation of the FeIII2
      Y* cofactor in RNR and the cellular iron-sulfur (Fe-S) protein biogenesis
      pathways by examining both the iron loading into the RNR beta subunit and the RNR
      catalytic activity in yeast mutants depleted of individual components of the
      mitochondrial iron-sulfur cluster assembly (ISC) and the CIA machineries. We
      found that both iron loading and cofactor assembly in RNR are dependent on the
      ISC machinery. We also found that Dre2 is required for RNR cofactor formation but
      appears to be dispensable for iron loading. None of the CIA components downstream
      of Dre2 was required for RNR cofactor formation. Thus, the pathways for RNR and
      Fe-S cluster biogenesis bifurcate after the Dre2-Tah18 step. We conclude that RNR
      cofactor biogenesis requires the ISC machinery to mature the Grx3/4 and Dre2 Fe-S
      proteins, which then function in iron and electron delivery to RNR, respectively.

PMID- 28515323
TI  - beta-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol
      exposure.
AB  - In liver steatosis (i.e. fatty liver), hepatocytes accumulate many large neutral
      lipid storage organelles known as lipid droplets (LDs). LDs are important in the
      maintenance of energy homeostasis, but the signaling mechanisms that stimulate LD
      metabolism in hepatocytes are poorly defined. In adipocytes, catecholamines
      target the beta-adrenergic (beta-AR)/cAMP pathway to activate cytosolic lipases
      and induce their recruitment to the LD surface. Therefore, the goal of this study
      was to determine whether hepatocytes, like adipocytes, also undergo cAMP-mediated
      lipolysis in response to beta-AR stimulation. Using primary rat hepatocytes and
      human hepatoma cells, we found that treatment with the beta-AR agent
      isoproterenol caused substantial LD loss via activation of cytosolic lipases
      adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). beta
      Adrenergic stimulation rapidly activated PKA, which led to the phosphorylation of
      ATGL and HSL and their recruitment to the LD surface. To test whether this beta
      AR-dependent lipolysis pathway was altered in a model of alcoholic fatty liver,
      primary hepatocytes from rats fed a 6-week EtOH-containing Lieber-DeCarli diet
      were treated with cAMP agonists. Compared with controls, EtOH-exposed hepatocytes
      showed a drastic inhibition in beta-AR/cAMP-induced LD breakdown and the
      phosphorylation of PKA substrates, including HSL. This observation was supported
      in VA-13 cells, an EtOH-metabolizing human hepatoma cell line, which displayed
      marked defects in both PKA activation and isoproterenol-induced ATGL
      translocation to the LD periphery. In summary, these findings suggest that beta
      AR stimulation mobilizes cytosolic lipases for LD breakdown in hepatocytes, and
      perturbation of this pathway could be a major consequence of chronic EtOH insult
      leading to fatty liver.

PMID- 28515325
TI  - Mutual regulation between Polo-like kinase 3 and SIAH2 E3 ubiquitin ligase
      defines a regulatory network that fine-tunes the cellular response to hypoxia and
      nickel.
AB  - Elevated cellular response to hypoxia, which contributes to cell transformation
      and tumor progression, is a prominent feature of malignant cells in solid tumors.
      Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase known to inhibit
      the cellular response to hypoxia and tumorigenesis. Nickel compounds are well
      established human carcinogens that induce tumorigenesis partly through their
      hypoxia-mimicking effects. Despite previous research efforts, the role of Plk3 in
      the hypoxic response induced by hypoxia or nickel is not completely understood.
      Here, we show that NiCl2 (Ni(II)) or hypoxia reduces the protein level and
      shortens the half-life of cytoplasmic Plk3 in a ubiquitin-proteasome-dependent
      manner. We identify SIAH2, a RING finger E3 ubiquitin ligase associated with the
      cellular hypoxic response, to be the ubiquitin E3 ligase that mediates the
      degradation of Plk3. We show that SIAH2 binds to Plk3 and mediates its
      ubiquitination primarily through its polo-box domain. We report that USP28, a
      deubiquitinase known to be inhibitable by Ni(II) or hypoxia, may also contribute
      to the suppression of the Plk3 protein by Ni(II). We also show that Plk3 in turn
      suppresses the SIAH2 protein level in a kinase activity-dependent manner. Our
      study revealed an interesting mutual regulation between Plk3 and SIAH2 and
      uncovered a regulatory network that functions to fine-tune the cellular hypoxic
      response. We propose that suppression of Plk3 expression contributes to
      carcinogenesis and tumor progression induced by nickel compounds.

PMID- 28515326
TI  - Semantic closure demonstrated by the evolution of a universal constructor
      architecture in an artificial chemistry.
AB  - We present a novel stringmol-based artificial chemistry system modelled on the
      universal constructor architecture (UCA) first explored by von Neumann. In a UCA,
      machines interact with an abstract description of themselves to replicate by
      copying the abstract description and constructing the machines that the abstract
      description encodes. DNA-based replication follows this architecture, with DNA
      being the abstract description, the polymerase being the copier, and the ribosome
      being the principal machine in expressing what is encoded on the DNA. This
      architecture is semantically closed as the machine that defines what the abstract
      description means is itself encoded on that abstract description. We present a
      series of experiments with the stringmol UCA that show the evolution of the
      meaning of genomic material, allowing the concept of semantic closure and
      transitions between semantically closed states to be elucidated in the light of
      concrete examples. We present results where, for the first time in an in silico
      system, simultaneous evolution of the genomic material, copier and constructor of
      a UCA, giving rise to viable offspring.

PMID- 28515327
TI  - Minimum action principle and shape dynamics.
AB  - In this paper, we propose a new method for computing a distance between two
      shapes embedded in three-dimensional space. Instead of comparing directly the
      geometric properties of the two shapes, we measure the cost of deforming one of
      the two shapes into the other. The deformation is computed as the geodesic
      between the two shapes in the space of shapes. The geodesic is found as a
      minimizer of the Onsager-Machlup action, based on an elastic energy for shapes
      that we define. Its length is set to be the integral of the action along that
      path; it defines an intrinsic quasi-metric on the space of shapes. We illustrate
      applications of our method to geometric morphometrics using three datasets
      representing bones and teeth of primates. Experiments on these datasets show that
      the variational quasi-metric we have introduced performs remarkably well both in
      shape recognition and in identifying evolutionary patterns, with success rates
      similar to, and in some cases better than, those obtained by expert observers.

PMID- 28515329
TI  - Inference of facultative mobility in the enigmatic Ediacaran organism
      Parvancorina.
AB  - Establishing how Ediacaran organisms moved and fed is critical to deciphering
      their ecological and evolutionary significance, but has long been confounded by
      their non-analogue body plans. Here, we use computational fluid dynamics to
      quantitatively analyse water flow around the Ediacaran taxon Parvancorina,
      thereby testing between competing models for feeding mode and mobility. The
      results show that flow was not distributed evenly across the organism, but was
      directed towards localized areas; this allows us to reject osmotrophy, and
      instead supports either suspension feeding or detritivory. Moreover, the patterns
      of recirculating flow differ substantially with orientation to the current,
      suggesting that if Parvancorina was a suspension feeder, it would have been most
      efficient if it was able to re-orient itself with respect to current direction,
      and thus ensure flow was directed towards feeding structures. Our simulations
      also demonstrate that the amount of drag varied with orientation, indicating that
      Parvancorina would have greatly benefited from adjusting its position to minimize
      drag. Inference of facultative mobility in Parvancorina suggests that Ediacaran
      benthic ecosystems might have possessed a higher proportion of mobile taxa than
      currently appreciated from trace fossil studies. Furthermore, this inference of
      movement suggests the presence of musculature or appendages that are not
      preserved in fossils, but which would noneltheless support a bilaterian affinity
      for Parvancorina.

PMID- 28515328
TI  - Mechanotransmission in endothelial cells subjected to oscillatory and multi
      directional shear flow.
AB  - Local haemodynamics are linked to the non-uniform distribution of atherosclerosic
      lesions in arteries. Low and oscillatory (reversing in the axial flow direction)
      wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs)
      mediating disease localization. The objective of this study is to investigate
      computationally how the flow direction (reflected in WSS variation on the EC
      surface over time) influences the forces experienced by structural components of
      ECs that are believed to play important roles in mechanotransduction. A three
      dimensional, multi-scale, multi-component, viscoelastic model of focally adhered
      ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel
      to the principal flow direction, or multi-directional oscillatory WSS with
      reversing axial and transverse components are applied over the EC surface. The
      computational model includes the glycocalyx layer, actin cortical layer, nucleus,
      cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs).
      We show the distinct effects of atherogenic flow profiles (reversing
      unidirectional flow and reversing multi-directional flow) on subcellular
      structures relative to non-atherogenic flow (non-reversing flow). Reversing flow
      lowers stresses and strains due to viscoelastic effects, and multi-directional
      flow alters stress on the ADJs perpendicular to the axial flow direction. The
      simulations predict forces on integrins, ADJ filaments and other substructures in
      the range that activate mechanotransduction.

PMID- 28515331
TI  - Cannibalism by damselflies increases with rising temperature.
AB  - Trophic interactions are likely to change under climate warming. These
      interactions can be altered directly by changing consumption rates, or indirectly
      by altering growth rates and size asymmetries among individuals that in turn
      affect feeding. Understanding these processes is particularly important for
      intraspecific interactions, as direct and indirect changes may exacerbate
      antagonistic interactions. We examined the effect of temperature on activity
      rate, growth and intraspecific size asymmetries, and how these temperature
      dependencies affected cannibalism in Lestes congener, a damselfly with marked
      intraspecific variation in size. Temperature increased activity rates and
      exacerbated differences in body size by increasing growth rates. Increased
      activity and changes in body size interacted to increase cannibalism at higher
      temperatures. We argue that our results are likely to be general to species with
      life-history stages that vary in their temperature dependencies, and that the
      effects of climate change on communities may depend on the temperature
      dependencies of intraspecific interactions.

PMID- 28515330
TI  - Post-fire recovery of torpor and activity patterns of a small mammal.
AB  - To cope with the post-fire challenges of decreased availability of food and
      shelter, brown antechinus (Antechinus stuartii), a small marsupial mammal,
      increase the use of energy-conserving torpor and reduce activity. However, it is
      not known how long it takes for animals to resume pre-fire torpor and activity
      patterns during the recovery of burnt habitat. Therefore, we tested the
      hypothesis that antechinus will adjust torpor use and activity after a fire
      depending on vegetation recovery. We simultaneously quantified torpor and
      activity patterns for female antechinus from three adjacent areas: (i) the area
      of a management burn 1 year post-fire, (ii) an area that was burned 2 years
      prior, and (iii) a control area. In comparison to shortly after the management
      burn, antechinus in all three groups displayed less frequent and less pronounced
      torpor while being more active. We provide the first evidence that only 1 year
      post-fire antechinus resume pre-fire torpor and activity patterns, probably in
      response to the return of herbaceous ground cover and foraging opportunities.

PMID- 28515332
TI  - The unusual tracheal system within the wing membrane of a dragonfly.
AB  - Some consider that the first winged insects had living tissue inside the wing
      membrane, resembling larval gills or developing wing pads. However, throughout
      the developmental process of the wing membrane of modern insects, cells and
      tracheoles in the lumen between dorsal and ventral cuticle disappear and both
      cuticles become fused. This process results in the rather thin rigid stable
      structure of the membrane. The herewith described remarkable case of the
      dragonfly Zenithoptera lanei shows that in some highly specialized wings, the
      membrane can still be supplemented by tracheae. Such a characteristic of the wing
      membrane presumably represents a strong specialization for the synthesis of
      melanin-filled nanolayers of the cuticle, nanospheres inside the wing membrane
      and complex arrangement of wax crystals on the membrane surface, all responsible
      for unique structural coloration.

PMID- 28515333
TI  - Effective cybersecurity is fundamental to patient safety.

PMID- 28515334
TI  - Central-acting therapeutics alleviate respiratory weakness caused by heart
      failure-induced ventilatory overdrive.
AB  - Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea
      and exertional fatigue. Most studies have focused on advanced stages of HF,
      leaving the cause unresolved. The long-standing theory is that pulmonary edema
      imposes a mechanical stress, resulting in diaphragmatic remodeling, but stable HF
      patients rarely exhibit pulmonary edema. We investigated how diaphragmatic
      weakness develops in two mouse models of pressure overload-induced HF. As in HF
      patients, both models had increased eupneic respiratory pressures and ventilatory
      drive. Despite the absence of pulmonary edema, diaphragmatic strength
      progressively declined during pressure overload; this decline correlated with a
      reduction in diaphragm cross-sectional area and preceded evidence of muscle
      weakness. We uncovered a functional codependence between angiotensin II and beta
      adrenergic (beta-ADR) signaling, which increased ventilatory drive. Chronic
      overdrive was associated with increased PERK (double-stranded RNA-activated
      protein kinase R-like ER kinase) expression and phosphorylation of EIF2alpha
      (eukaryotic translation initiation factor 2alpha), which inhibits protein
      synthesis. Inhibition of beta-ADR signaling after application of pressure
      overload normalized diaphragm strength, Perk expression, EIF2alpha
      phosphorylation, and diaphragmatic cross-sectional area. Only drugs that were
      able to penetrate the blood-brain barrier were effective in treating ventilatory
      overdrive and preventing diaphragmatic atrophy. These data provide insight into
      why similar drugs have different benefits on mortality and symptomatology,
      despite comparable cardiovascular effects.

PMID- 28515337
TI  - Hung over? Maybe it's your overactive microglia.
AB  - Acute ethanol intake is associated with a mild suppression of microglial activity
      followed by a more robust inflammatory reaction during the withdrawal period.

PMID- 28515335
TI  - In situ bone tissue engineering via ultrasound-mediated gene delivery to
      endogenous progenitor cells in mini-pigs.
AB  - More than 2 million bone-grafting procedures are performed each year using
      autografts or allografts. However, both options carry disadvantages, and there
      remains a clear medical need for the development of new therapies for massive
      bone loss and fracture nonunions. We hypothesized that localized ultrasound
      mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells
      would induce efficient bone regeneration and fracture repair. To test this
      hypothesis, we surgically created a critical-sized bone fracture in the tibiae of
      Yucatan mini-pigs, a clinically relevant large animal model. A collagen scaffold
      was implanted in the fracture to facilitate recruitment of endogenous mesenchymal
      stem/progenitor cells (MSCs) into the fracture site. Two weeks later,
      transcutaneous ultrasound-mediated reporter gene delivery successfully
      transfected 40% of cells at the fracture site, and flow cytometry showed that 80%
      of the transfected cells expressed MSC markers. Human bone morphogenetic protein
      6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model,
      leading to transient expression and secretion of BMP-6 localized to the fracture
      area. Micro-computed tomography and biomechanical analyses showed that ultrasound
      mediated BMP-6 gene delivery led to complete radiographic and functional fracture
      healing in all animals 6 weeks after treatment, whereas nonunion was evident in
      control animals. Collectively, these findings demonstrate that ultrasound
      mediated gene delivery to endogenous mesenchymal progenitor cells can effectively
      treat nonhealing bone fractures in large animals, thereby addressing a major
      orthopedic unmet need and offering new possibilities for clinical translation.

PMID- 28515338
TI  - An "eye" for rhythm.
AB  - A new analytical method allows reconstruction of circadian gene expression in
      human biopsy samples.

PMID- 28515336
TI  - The effects of micronutrient deficiencies on bacterial species from the human gut
      microbiota.
AB  - Vitamin and mineral (micronutrient) deficiencies afflict 2 billion people.
      Although the impact of these imbalances on host biology has been studied
      extensively, much less is known about their effects on the gut microbiota of
      developing or adult humans. Therefore, we established a community of cultured,
      sequenced human gut-derived bacterial species in gnotobiotic mice and fed the
      animals a defined micronutrient-sufficient diet, followed by a derivative diet
      devoid of vitamin A, folate, iron, or zinc, followed by return to the sufficient
      diet. Acute vitamin A deficiency had the largest effect on bacterial community
      structure and metatranscriptome, with Bacteroides vulgatus, a prominent
      responder, increasing its abundance in the absence of vitamin A. Applying retinol
      selection to a library of 30,300 B. vulgatus transposon mutants revealed that
      disruption of acrR abrogated retinol sensitivity. Genetic complementation
      studies, microbial RNA sequencing, and transcription factor-binding assays
      disclosed that AcrR is a repressor of an adjacent AcrAB-TolC efflux system.
      Retinol efflux measurements in wild-type and acrR-mutant strains plus treatment
      with a pharmacologic inhibitor of the efflux system revealed that AcrAB-TolC is a
      determinant of retinol and bile acid sensitivity in B. vulgatus Acute vitamin A
      deficiency was associated with altered bile acid metabolism in vivo, raising the
      possibility that retinol, bile acid metabolites, and AcrAB-TolC interact to
      influence the fitness of B. vulgatus and perhaps other microbiota members. This
      type of preclinical model can help to develop mechanistic insights about the
      effects of, and more effective treatment strategies for micronutrient
      deficiencies.

PMID- 28515339
TI  - Chemotherapy-treated cells go up in flames.
AB  - Apoptosis induced by chemotherapies can also trigger proinflammatory pyroptosis.

PMID- 28515340
TI  - Turning back the clock.
AB  - Increased DNA breaks in aging skeletal muscle activate the DNA-PK pathway,
      whereas blocking this pathway improves mitochondrial density, physical fitness,
      body weight, and insulin resistance in mice.

PMID- 28515342
TI  - Clinical presentations and epidemiology of vascular dementia.
AB  - Cerebrovascular and cardiovascular diseases cause vascular brain injury that can
      lead to vascular cognitive impairment (VCI). VCI is the second most common
      neuropathology of dementia and mild cognitive impairment (MCI), accounting for up
      to one-third of the population risk. It is frequently present along with other
      age-related pathologies such as Alzheimer's disease (AD). Multiple etiology
      dementia with both VCI and AD is the single most common cause of later life
      dementia. There are two main clinical syndromes of VCI: post-stroke VCI in which
      cognitive impairment is the immediate consequence of a recent stroke and VCI
      without recent stroke in which cognitive impairment is the result of covert
      vascular brain injury detected only on neuroimaging or neuropathology. VCI is a
      syndrome that can result from any cause of infarction, hemorrhage, large artery
      disease, cardioembolism, small vessel disease, or other cerebrovascular or
      cardiovascular diseases. Secondary prevention of further vascular brain injury
      may improve outcomes in VCI.

PMID- 28515343
TI  - Kidney, heart and brain: three organs targeted by ageing and glycation.
AB  - Advanced glycation end-product (AGE) is the generic term for a heterogeneous
      group of derivatives arising from a non-enzymatic reaction between reducing
      sugars and proteins. In recent years, evidence has accumulated that incriminates
      AGEs in pathogenic processes associated with both chronic hyperglycaemia and age
      related diseases. Regardless of their exogenous or endogenous origin, the
      accumulation of AGEs and their derivatives could promote accelerated ageing by
      leading to protein modifications and activating several inflammatory signalling
      pathways via AGE-specific receptors. However, it remains to be demonstrated
      whether preventing the accumulation of AGEs and their effects is an important
      therapeutic option for successful ageing. The present review gives an overview of
      the current knowledge on the pathogenic role of AGEs by focusing on three AGE
      target organs: kidney, heart and brain. For each of these organs we concentrate
      on an age-related disease, each of which is a major public health issue: chronic
      kidney disease, heart dysfunction and neurodegenerative diseases. Even though
      strong connections have been highlighted between glycation and age-related
      pathogenesis, causal links still need to be validated. In each case, we report
      evidence and uncertainties suggested by animal or epidemiological studies on the
      possible link between pathogenesis and glycation in a chronic hyperglycaemic
      state, in the absence of diabetes, and with exogenous AGEs alone. Finally, we
      present some promising anti-AGE strategies that are currently being studied.

PMID- 28515341
TI  - BET bromodomain inhibition suppresses innate inflammatory and profibrotic
      transcriptional networks in heart failure.
AB  - Despite current standard of care, the average 5-year mortality after an initial
      diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new
      therapeutic approaches. Previous studies demonstrated that the epigenetic reader
      protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target
      in cancer, functions as a critical coactivator of pathologic gene transactivation
      during cardiomyocyte hypertrophy. However, the therapeutic relevance of these
      findings to human disease remained unknown. We demonstrate that treatment with
      the BET bromodomain inhibitor JQ1 has therapeutic effects during severe,
      preestablished HF from prolonged pressure overload, as well as after a massive
      anterior myocardial infarction in mice. Furthermore, JQ1 potently blocks agonist
      induced hypertrophy in human induced pluripotent stem cell-derived cardiomyocytes
      (iPSC-CMs). Integrated transcriptomic analyses across animal models and human
      iPSC-CMs reveal that BET inhibition preferentially blocks transactivation of a
      common pathologic gene regulatory program that is robustly enriched for NFkappaB
      and TGF-beta signaling networks, typified by innate inflammatory and profibrotic
      myocardial genes. As predicted by these specific transcriptional mechanisms, we
      found that JQ1 does not suppress physiological cardiac hypertrophy in a mouse
      swimming model. These findings establish that pharmacologically targeting innate
      inflammatory and profibrotic myocardial signaling networks at the level of
      chromatin is effective in animal models and human cardiomyocytes, providing the
      critical rationale for further development of BET inhibitors and other epigenomic
      medicines for HF.

PMID- 28515344
TI  - Kidney-brain axis inflammatory cross-talk: from bench to bedside.
AB  - Epidemiologic data suggest that individuals at all stages of chronic kidney
      disease (CKD) have a higher risk of developing neuropsychiatric disorders,
      cognitive impairment, and dementia. This risk is generally explained by the high
      prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions.
      However, other potential mechanisms, including cytokine/chemokine release,
      production of reactive oxygen species (ROS), circulating and local formation of
      trophic factors and of renin-angiotensin system (RAS) molecules, could also be
      involved, especially in the absence of obvious cerebrovascular disease. In this
      review, we discuss experimental and clinical evidence for the role of these
      mechanisms in kidney-brain cross-talk. In addition, we hypothesize potential
      pathways for the interactions between kidney and brain and their
      pathophysiological role in neuropsychiatric and cognitive changes found in
      patients with CKD. Understanding the pathophysiologic interactions between renal
      impairment and brain function is important in order to minimize the risk for
      future cognitive impairment and to develop new strategies for innovative
      pharmacological treatment.

PMID- 28515345
TI  - Genetic factors associated with risk of metabolic syndrome and hepatocellular
      carcinoma.
AB  - Although the metabolic syndrome is a commonplace topic, its potential threats to
      public health is a problem that cannot be neglected. As the living conditions
      improved significantly over the past few years, the morbidity of metabolic
      syndrome has also steadily risen, and the onset age is becoming younger. The
      hepatocellular carcinoma (HCC), is one of the most prevalent life-threatening
      human cancers worldwide, incidence of which is also on the rise, gradually
      occupied the top of the list associated with metabolic syndrome related
      complication. Despite the advanced improvement of HCC management, the lifestyle,
      environmental factors, obesity, hepatitis B virus (HBV) infection have been
      recognized as risk factors for the development of liver cancer. In recent years,
      genetic studies, especially the genome-wide association studies (GWASs) were
      widely performed, a new era of the human genome research was created, which has
      significantly promoted the study of complex disease genetics. These progresses
      have contributed to the discovery of abundant number of genomic loci convincingly
      linked with complex metabolic feature and HCC. In this review, we briefly
      summarize the association between metabolic syndrome and HCC, focusing on the
      genetic factors contributed to metabolic syndrome and HCC.

PMID- 28515348
TI  - Relation of phosphodiesterase type 5 inhibitors and malignant melanoma: a meta
      analysis and systematic review.
AB  - Data on the association between using PDE5 inhibitors and malignant melanoma are
      conflicting. To estimate the relation of using PDE5 inhibitors with risk of
      malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up
      to February 2017, and a random effects model was used to calculate the summary
      risk estimates. Five observational studies were included. Five studies reports
      encompassed a total of 15,979 melanoma cases occurring among 1, 188,414
      participants. The pooled multivariable-adjusted RR of melanoma in patients with
      using PDE5 inhibitors was 1.12 (95% CI: 1.03-1.21, I2 = 0.48). Findings from this
      systematic review support that PDE5 inhibitor use is associated with increased
      risk of melanoma in ED patients, the result remains inclusive and warrants
      further study in the future.

PMID- 28515346
TI  - The novel complex combination of alum, CpG ODN and HH2 as adjuvant in cancer
      vaccine effectively suppresses tumor growth in vivo.
AB  - Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2
      response. So, the development of combinatorial adjuvants inducing a robust mixed
      Th1/Th2 response is a promising vaccination strategy against cancer. Here, we
      describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide
      (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune
      responses. The CpG-HH2 complex significantly enhanced the production of IFN
      gamma, TNF-alpha and IL-1beta, promoted the uptake of antigen and strengthened
      the activation of p38, Erk1/2 and NF-kappaB in vitro, compared to CpG or HH2
      alone. Immunization with NY-ESO-1 antigen plus alum-CpG-HH2 combinatorial
      adjuvant effectively inhibited tumor growth and reduced tumor burden in
      prophylactic and therapeutic tumor models and even in passive serum or cellular
      therapy. In addition, co-administration of NY-ESO-1 with alum-CpG-HH2
      combinatorial adjuvant markedly activated NK cell cytotoxicity, induced antibody
      dependent cellular cytotoxicity (ADCC), dramatically elicited cytotoxic T
      lymphocytes (CTLs) response, and increased infiltrating lymphocytes in tumors.
      Moreover, in vivo depletion of CD8+ T cells completely and depletion of NK cells
      partially blocked the anti-tumor activity of NY-ESO-1-alum-CpG-HH2 immunization.
      Overall, our results demonstrate a novel adjuvant combination for cancer vaccine
      with efficient immunomodulation by stimulating innate immunity and mediating
      adaptive immunity.

PMID- 28515349
TI  - APC hypermethylation for early diagnosis of colorectal cancer: a meta-analysis
      and literature review.
AB  - Adenomatous polyposis coli (APC) promoter hypermethylation has been frequently
      observed in colorectal cancer (CRC). The association between APC promoter
      methylation and clinicopathological significance in CRC is under investigation.
      We performed a meta-analysis to quantitatively evaluate the significance of APC
      methylation in CRC. The study included a total of 24 articles and 2025 CRC
      patients. The frequency of APC promoter hypermethylation was significantly higher
      in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45
      13.56; p<0.0001, I2=0%. APC promoter more frequently hypermethylated in CRC stage
      I compared to normal colorectal tissue, OR was 13.42, 95% CI, 3.66-49.20;
      p<0.0001, I2=31%. The risk of incidence of CRC was significantly correlated to
      APC promoter hypermethylation, pooled OR was 9.80, 95%CI, 6.07-15.81; p<0.00001,
      I2=43%. APC methylation was not associated with grade, stage of CRC as well as
      tumor location, patients' gender, and smoking behavior. The results indicate that
      APC promoter hypermethylation is an early event in carcinogenesis of CRC, could
      be a valuable diagnostic marker for early-stage CRC. APC methylation is not
      significantly associated with overall survival in patients with CRC. APC is a
      potential drug target for development of personalized treatment.

PMID- 28515350
TI  - FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2
      receptor-Akt signaling pathway.
AB  - FAM3A plays important roles in regulating hepatic glucose/lipid metabolism and
      the proliferation of VSMCs. This study determined the role and mechanism of FAM3A
      in the adipogenesis of 3T3-L1 preadipocytes. During the adipogenesis of 3T3-L1
      preadipocytes, FAM3A expression was significantly increased. FAM3A overexpression
      enhanced 3T3-L1 preadipocyte adipogenesis with increased phosphorylated Akt
      (pAkt) level, whereas FAM3A silencing inhibited 3T3-L1 preadipocyte adipogenesis
      with reduced pAkt level. Moreover, FAM3A silencing reduced the expression and
      secretion of adipokines in 3T3-L1 cells. FAM3A protein is mainly located in
      mitochondrial fraction of 3T3-L1 cells and mouse adipose tissue. FAM3A
      overexpression increased, whereas FAM3A silencing decreased ATP production in 3T3
      L1 preadipocytes. FAM3A-induced adipogenesis of 3T3-L1 preadipocytes was blunted
      by inhibitor of P2 receptor. In white adipose tissues of db/db and HFD-fed obese
      mice, FAM3A expression was reduced. One-month rosiglitazone administration
      upregulated FAM3A expression, and increased cellular ATP content and pAkt level
      in white adipose tissues of normal and obese mice. In conclusion, FAM3A enhances
      the adipogenesis of preadipocytes by activating ATP-P2 receptor-Akt pathway.
      Under obese condition, a decrease in FAM3A expression in adipose tissues plays
      important roles in the development of adipose dysfunction and type 2 diabetes.

PMID- 28515351
TI  - Local immune response depends on p16INK4a status of primary tumor in vulvar
      squamous cell carcinoma.
AB  - BACKGROUND: The p16Ink4a is not a surrogate marker for high-risk human papilloma
      virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell
      carcinoma patients. Our recent study confirmed substantial mismatch between
      p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a
      overexpression itself is an independent prognostic factor for vulvar cancer. AIM:
      To determine significance of the tumor infiltrating immune cells and p16Ink4a
      status for better outcome of patients with vulvar cancer. METHODS:
      Intraepithelial tumor infiltrating lymphocytes: CD8+, CD4+, FOXP3+, CD56+, tumor
      associated macrophages: CD68+, and GZB+ cells were calculated in 85 vulvar
      squamous cell carcinomas with previously defined p16Ink4a and high-risk HPV
      status. Number of intraepithelial CD8+, CD4+, FOXP3+, CD56+, CD68+ and GZB+ cells
      were compared between tumors with different p16INK4a status and overlapping high
      risk HPV-status separately. Survival analyses included the Kaplan-Meier method,
      log-rank test and Cox proportional hazards model. RESULTS: p16Ink4a-negative
      tumors were more infiltrated by intraepithelial CD8+, CD4+ and GZB+ cells than
      p16Ink4a-positive tumors (p=0.032, p=0.016 and p=0.007 respectively). High-risk
      HPV-status did not correlate with the infiltration of immune cells. Median follow
      up was 89.20 months (range 1.7-189.5). High CD4+ and CD56+ indices were
      correlated with prognosis in p16Ink4a-positive cases (p=0.039 and p=0.013
      respectively). Low CD68+ infiltrates were correlated with prognosis in p16Ink4a
      negative cases (p=0.018). CONCLUSION: p16Ink4a-status impacts local immune
      surveillance as represented by tumor infiltrating immune cells. Immunologic
      effects contributing to clinical outcome might depend on p16Ink4a-overexpression.

PMID- 28515352
TI  - Intensity-modulated radiotherapy provides better quality of life than two
      dimensional conventional radiotherapy for patients with stage II nasopharyngeal
      carcinoma.
AB  - Two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated
      radiotherapy (IMRT) are effective for control of nasopharyngeal carcinoma (NPC).
      The purpose of this study was to compare the quality of life (QoL) of stage II
      NPC patients treated with 2D-CRT versus IMRT. We conducted a cross-sectional
      study of 106 patients with stage II NPC treated with 2D-CRT (n = 47) versus IMRT
      (n = 59) between June 2008 and June 2013. For all subjects, disease-free survival
      was more than 3 years. QoL was assessed using the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ
      C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. Patients
      receiving IMRT with or without concurrent chemotherapy had better outcomes in
      head and neck related symptoms and general aspects of QoL than those receiving 2D
      CRT with or without concurrent chemotherapy. Thus, IMRT improves the QoL of
      patients with stage II NPC as compared to 2D-CRT.

PMID- 28515355
TI  - Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil
      through a miRNA-dependent mechanism.
AB  - 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal
      cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA
      expression. In addition, it has been reported that 5-FU incorporates into the
      RNAs constituting the translational machinery and that 5-FU affects the amount of
      some mRNAs associated with ribosomes. However, the impact of 5-FU on
      translational regulation remains unclear. Using translatome profiling, we report
      that a clinically relevant dose of 5-FU induces a translational reprogramming in
      colorectal cancer cell lines. Comparison of mRNA distribution between polysomal
      and non-polysomal fractions in response to 5-FU treatment using microarray
      quantification identified 313 genes whose translation was selectively regulated.
      These regulations were mostly stimulatory (91%). Among these genes, we showed
      that 5-FU increases the mRNA translation of HIVEP2, which encodes a transcription
      factor whose translation in normal condition is known to be inhibited by mir-155.
      In response to 5-FU, the expression of mir-155 decreases thus stimulating the
      translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific
      mRNA translation was associated with reduction of global protein synthesis.
      Altogether, these findings indicate that 5-FU promotes a translational
      reprogramming leading to the increased translation of a subset of mRNAs that
      involves at least for some of them, miRNA-dependent mechanisms. This study
      supports a still poorly evaluated role of translational control in drug response.

PMID- 28515357
TI  - E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in
      the liver.
AB  - Cholesterol accumulation in the liver is an early event in nonalcoholic fatty
      liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in
      maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via
      proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low
      density lipoprotein receptor (LDLR) degradation upon activation. E2f1-/- mice
      display reduced total plasma cholesterol levels and increased cholesterol content
      in the liver. In this study, we show that E2f1 deletion in cellular and mouse
      models leads to a marked decrease in Pcsk9 expression and an increase in LDLR
      expression. In addition to the upregulation of LDLR, we report that E2f1-/-
      hepatocytes exhibit increased LDL uptake. ChIP-Seq and PCSK9 promoter reporter
      experiments confirmed that E2F1 binds to and transactivates the PCSK9 promoter.
      Interestingly, E2f1-/- mice fed a high-cholesterol diet (HCD) display a fatty
      liver phenotype and liver fibrosis, which is reversed by reexpression of PCSK9 in
      the liver. Collectively, these data indicate that E2F1 regulates cholesterol
      uptake and that the loss of E2F1 leads to abnormal cholesterol accumulation in
      the liver and the development of fibrosis in response to an HCD.

PMID- 28515356
TI  - Licensing delineates helper and effector NK cell subsets during viral infection.
AB  - Natural killer (NK) cells can be divided into phenotypic subsets based on
      expression of receptors that bind self-MHC-I molecules, a concept termed
      licensing or education. Here we show NK cell subsets with different migratory,
      effector, and immunoregulatory functions in dendritic cell and antigen (ag)
      specific CD8+ T cell responses during influenza and murine cytomegalovirus
      infections. Shortly after infection, unlicensed NK cells localized in draining
      lymph nodes and produced GM-CSF, which correlated with the expansion and
      activation of dendritic cells, and resulted in greater and sustained ag-specific
      T cell responses. In contrast, licensed NK cells preferentially migrated to
      infected tissues and produced IFN-gamma. Importantly, human NK cell subsets
      exhibited similar phenotypic characteristics. Collectively, our studies
      demonstrate a critical demarcation between the functions of licensed and
      unlicensed NK cell subsets, with the former functioning as the classical effector
      subset and the latter as the stimulator of adaptive immunity helping to prime
      immune responses.

PMID- 28515359
TI  - T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and
      continued thymic microenvironment interaction.
AB  - Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic
      stem cell transplant aids the recovery of the thymus damaged by total body
      irradiation. To understand the interaction between proTs and the thymic
      microenvironment, WT mice were lethally irradiated and given T cell-deficient
      (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell
      development to infused proTs. ProTs within the host thymus led to a significant
      increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing
      actively cycling TECs. Upon thymus egress (day 28), proT TEC effects were lost,
      suggesting that continued signaling from proTs is required to sustain TEC cycling
      and cellularity. Thymocytes increased significantly by day 21, followed by a
      significant improvement in mature T cell numbers in the periphery by day 35. This
      protective surge was temporary, receding by day 60. Double-negative 2 (DN2) proTs
      selectively increased thymocyte number, while DN3 proTs preferentially increased
      TECs and T cells in the spleen that persisted at day 60. These findings highlight
      the importance of the interaction between proTs and TECs in the proliferation and
      survival of TECs and that the maturation stage of proTs has unique effects on
      thymopoiesis and peripheral T cell recovery.

PMID- 28515358
TI  - IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway
      hyperreactivity in mice.
AB  - Severe asthma (SA) is a significant problem both clinically and economically,
      given its poor response to corticosteroids (CS). We recently reported a complex
      type 1-dominated (IFN-gamma-dominated) immune response in more than 50% of severe
      asthmatics despite high-dose CS treatment. Also, IFN-gamma was found to be
      critical for increased airway hyperreactivity (AHR) in our model of SA. The
      transcription factor IRF5 expressed in M1 macrophages can induce a Th1/Th17
      response in cocultured human T cells. Here we show markedly higher expression of
      IRF5 in bronchoalveolar lavage (BAL) cells of severe asthmatics as compared with
      that in cells from milder asthmatics or healthy controls. Using our SA mouse
      model, we demonstrate that lack of IRF5 in lymph node migratory DCs severely
      limits their ability to stimulate the generation of IFN-gamma- and IL-17
      producing CD4+ T cells and IRF5-/- mice subjected to the SA model displayed
      significantly lower IFN-gamma and IL-17 responses, albeit showing a reciprocal
      increase in Th2 response. However, the absence of IRF5 rendered the mice
      responsive to CS with suppression of the heightened Th2 response. These data
      support the notion that IRF5 inhibition in combination with CS may be a viable
      approach to manage disease in a subset of severe asthmatics.

PMID- 28515360
TI  - A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell
      production.
AB  - The Psmb11-encoded beta5t subunit of the thymoproteasome, which is specifically
      expressed in cortical thymic epithelial cells (cTECs), is essential for the
      optimal positive selection of functionally competent CD8+ T cells in mice. Here,
      we report that a human genomic PSMB11 variation, which is detectable at an
      appreciable allele frequency in human populations, alters the beta5t amino acid
      sequence that affects the processing of catalytically active beta5t proteins. The
      introduction of this variation in the mouse genome revealed that the
      heterozygotes showed reduced beta5t expression in cTECs and the homozygotes
      further exhibited reduction in the cellularity of CD8+ T cells. No severe health
      problems were noticed in many heterozygous and 5 homozygous human individuals.
      Long-term analysis of health status, particularly in the homozygotes, is expected
      to improve our understanding of the role of the thymoproteasome-dependent
      positive selection of CD8+ T cells in humans.

PMID- 28515361
TI  - Lupus and proliferative nephritis are PAD4 independent in murine models.
AB  - Though recent reports suggest that neutrophil extracellular traps (NETs) are a
      source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we
      recently showed that inhibition of NETs by targeting the NADPH oxidase complex
      via cytochrome b-245, beta polypeptide (cybb) deletion exacerbated disease in the
      MRL.Faslpr lupus mouse model. While these data challenge the paradigm that NETs
      promote lupus, it is conceivable that global regulatory properties of cybb and
      cybb-independent NETs confound these findings. Furthermore, recent reports
      indicate that inhibitors of peptidyl arginine deiminase, type IV (Padi4), a
      distal mediator of NET formation, improve lupus in murine models. Here, to
      clarify the contribution of NETs to SLE, we employed a genetic approach to delete
      Padi4 in the MRL.Faslpr model and used a pharmacological approach to inhibit PADs
      in both the anti-glomerular basement membrane model of proliferative nephritis
      and a human-serum-transfer model of SLE. In contrast to prior inhibitor studies,
      we found that deletion of Padi4 did not ameliorate any aspect of nephritis, loss
      of tolerance, or immune activation. Pharmacological inhibition of PAD activity
      had no effect on end-organ damage in inducible models of glomerulonephritis.
      These data provide a direct challenge to the concept that NETs promote
      autoimmunity and target organ injury in SLE.

PMID- 28515362
TI  - Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor
      disease progression.
AB  - Advanced cancer induces fundamental changes in metabolism and promotes cardiac
      atrophy and heart failure. We discovered systemic insulin deficiency in cachectic
      cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or
      colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with
      marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors
      decrease systemic insulin via high glucose consumption, lowering pancreatic
      insulin production and producing insulin-degrading enzyme. As tumor cells consume
      glucose in an insulin-independent manner, they shift glucose away from
      cardiomyocytes. Since cardiomyocytes in both tumor models remained insulin
      responsive, low-dose insulin supplementation by subcutaneous implantation of
      insulin-releasing pellets improved cardiac glucose uptake, atrophy, and function,
      with no adverse side effects. In addition, by redirecting glucose to the heart in
      addition to other organs, the systemic insulin treatment lowered glucose usage by
      the tumor and thereby decreased tumor growth and volume. Insulin corrected the
      cancer-induced reduction in cardiac Akt activation and the subsequent
      overactivation of the proteasome and autophagy. Thus, cancer-induced systemic
      insulin depletion contributes to cardiac wasting and failure and may promote
      tumor growth. Low-dose insulin supplementation attenuates these processes and may
      be supportive in cardio-oncologic treatment concepts.

PMID- 28515363
TI  - Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12
      production.
AB  - DCs are necessary and sufficient for induction of allergic airway inflammation.
      CD11b+ DCs direct the underlying Th2 immunity, but debate surrounds the function
      of CD103+ DCs in lung immunity and asthma after an allergic challenge. We
      challenged Batf3-/- mice, which lacked lung CD103+ DCs, with the relevant
      allergen house dust mite (HDM) as a model to ascertain their role in asthma. We
      show that acute and chronic HDM exposure leads to defective Th1 immunity in Batf3
      deficient mice. In addition, chronic HDM challenge in Batf3-/- mice results in
      increased Th2 and Th17 immune responses and exacerbated airway inflammation.
      Mechanistically, Batf3 absence does not affect induction of Treg or IL-10
      production by lung CD4+ T cells following acute HDM challenge. Batf3-dependent
      CD103+ migratory DCs are the main source of IL-12p40 in the mediastinal lymph
      node DC compartment in the steady state. Moreover, CD103+ DCs selectively
      increase their IL-12p40 production upon HDM administration. In vivo IL-12
      treatment reverts exacerbated allergic airway inflammation upon chronic HDM
      challenge in Batf3-/- mice, restraining Th2 and Th17 responses without triggering
      Th1 immunity. These results suggest a protective role for lung CD103+ DCs to HDM
      allergic airway inflammation through the production of IL-12.

PMID- 28515365
TI  - Ceramide synthesis regulates T cell activity and GVHD development.
AB  - Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective
      immunotherapy for a variety of hematologic malignances, yet its efficacy is
      impeded by the development of graft-versus-host disease (GVHD). GVHD is
      characterized by activation, expansion, cytokine production, and migration of
      alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable.
      Ceramides are known to contribute to inflammation and autoimmunity. However,
      their involvement in T-cell responses to alloantigens is undefined. In the
      current study, we specifically characterized the role of ceramide synthase 6
      (CerS6) after allo-HCT using genetic and pharmacologic approaches. We found that
      CerS6 was required for optimal T cell activation, proliferation, and cytokine
      production in response to alloantigen and for subsequent induction of GVHD.
      However, CerS6 was partially dispensable for the T cell-mediated antileukemia
      effect. At the molecular level, CerS6 was required for efficient TCR signal
      transduction, including tyrosine phosphorylation, ZAP-70 activation, and
      PKCtheta/TCR colocalization. Impaired generation of C16-ceramide was responsible
      for diminished allogeneic T cell responses. Furthermore, targeting CerS6 using a
      specific inhibitor significantly reduced T cell activation in mouse and human T
      cells in vitro. Our study provides a rationale for targeting CerS6 to control
      GVHD, which would enhance the efficacy of allo-HCT as an immunotherapy for
      hematologic malignancies in the clinic.

PMID- 28515364
TI  - Nicotinamide metabolism regulates glioblastoma stem cell maintenance.
AB  - Metabolic dysregulation promotes cancer growth through not only energy
      production, but also epigenetic reprogramming. Here, we report that a critical
      node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked
      among the most consistently overexpressed metabolism genes in glioblastoma
      relative to normal brain. NNMT was preferentially expressed by mesenchymal
      glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a
      methyl donor generated from methionine. GSCs contained lower levels of
      methionine, SAM, and nicotinamide, but they contained higher levels of oxidized
      nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells. In
      concordance with the poor prognosis associated with DNA hypomethylation in
      glioblastoma, depletion of methionine, a key upstream methyl group donor, shifted
      tumors toward a mesenchymal phenotype and accelerated tumor growth. Targeting
      NNMT expression reduced cellular proliferation, self-renewal, and in vivo tumor
      growth of mesenchymal GSCs. Supporting a mechanistic link between NNMT and DNA
      methylation, targeting NNMT reduced methyl donor availability, methionine levels,
      and unmethylated cytosine, with increased levels of DNA methyltransferases, DNMT1
      and DNMT3A. Supporting the clinical significance of these findings, NNMT
      portended poor prognosis for glioblastoma patients. Collectively, our findings
      support NNMT as a GSC-specific therapeutic target in glioblastoma by disrupting
      oncogenic DNA hypomethylation.

PMID- 28515366
TI  - Experimental lupus is aggravated in mouse strains with impaired induction of
      neutrophil extracellular traps.
AB  - Many effector mechanisms of neutrophils have been implicated in the pathogenesis
      of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have
      been assigned a particularly detrimental role. Here we investigated the
      functional impact of neutrophils and NETs on a mouse model of lupus triggered by
      intraperitoneal injection of the cell death-inducing alkane pristane. Pristane
      induced lupus (PIL) was aggravated in 2 mouse strains with impaired induction of
      NET formation, i.e., NOX2-deficient (Ncf1-mutated) and peptidyl arginine
      deiminase 4-deficient (PAD4-deficient) mice, as seen from elevated levels of
      antinuclear autoantibodies (ANAs) and exacerbated glomerulonephritis. We observed
      a dramatically reduced ability to form pristane-induced NETs in vivo in both Ncf1
      mutated and PAD4-deficient mice, accompanied by higher levels of inflammatory
      mediators in the peritoneum. Similarly, neutropenic Mcl-1DeltaMyelo mice
      exhibited higher levels of ANAs, which indicates a regulatory function in lupus
      of NETs and neutrophils. Blood neutrophils from Ncf1-mutated and human
      individuals with SLE exhibited exuberant spontaneous NET formation. Treatment
      with specific chemical NOX2 activators induced NET formation and ameliorated PIL.
      Our findings suggest that aberrant NET is one of the factors promoting
      experimental lupus-like autoimmunity by uncontrolled release of inflammatory
      mediators.

PMID- 28515367
TI  - Association of impaired neuronal migration with cognitive deficits in extremely
      preterm infants.
AB  - Many extremely preterm infants (born before 28 gestational weeks [GWs]) develop
      cognitive impairment in later life, although the underlying pathogenesis is not
      yet completely understood. Our examinations of the developing human neocortex
      confirmed that neuronal migration continues beyond 23 GWs, the gestational week
      at which extremely preterm infants have live births. We observed larger numbers
      of ectopic neurons in the white matter of the neocortex in human extremely
      preterm infants with brain injury and hypothesized that altered neuronal
      migration may be associated with cognitive impairment in later life. To confirm
      whether preterm brain injury affects neuronal migration, we produced brain damage
      in mouse embryos by occluding the maternal uterine arteries. The mice showed
      delayed neuronal migration, ectopic neurons in the white matter, altered neuronal
      alignment, and abnormal corticocortical axonal wiring. Similar to human extremely
      preterm infants with brain injury, the surviving mice exhibited cognitive
      deficits. Activation of the affected medial prefrontal cortices of the surviving
      mice improved working memory deficits, indicating that decreased neuronal
      activity caused the cognitive deficits. These findings suggest that altered
      neuronal migration altered by brain injury might contribute to the subsequent
      development of cognitive impairment in extremely preterm infants.

PMID- 28515369
TI  - Effect of Reverse Vessel Remodeling on Regression of Coronary Atherosclerosis in
      Patients Treated With Aggressive Lipid- and Blood Pressure-Lowering Therapy -
      Insight From MILLION Study.
AB  - BACKGROUND: The MILLION study, a prospective randomized multicenter study,
      revealed that lipid and blood pressure (BP)-lowering therapy resulted in
      regression of coronary plaque as determined by intravascular ultrasound (IVUS).
      In the present study we performed additional analysis to investigate the
      associated factors with regression of coronary plaque.Methods and Results:We
      investigated serial 3D IVUS images from 68 patients in the MILLION study.
      Standard IVUS parameters were assessed at both baseline and follow-up (18-24
      months). Volumetric data were standardized by length as normalized volume. In
      patients with plaque regression (n=52), plaque volumenormalizedsignificantly
      decreased from 64.8 to 55.8 mm3(P<0.0001) and vessel
      volumenormalizedsignificantly decreased from 135.0 to 127.5 mm3(P=0.0008). There
      was no difference in lumen volumenormalizedfrom 70.1 to 71.8 mm3(P=0.27). There
      were no correlations between % changes in vessel volume and cholesterol or BP. On
      the other hand, negative correlations between % change in vessel volume and
      vessel volumenormalizedat baseline (r=-0.352, P=0.009) or plaque
      volumenormalizedat baseline (r=-0.336, P=0.01) were observed. CONCLUSIONS: The
      current data demonstrated that in patients with plaque regression treated by
      aggressive lipid and BP-lowering therapy, the plaque regression was derived from
      reverse vessel remodeling determined by vessel volume and plaque burden at
      baseline irrespective of decreases in lipids and BP.

PMID- 28515370
TI  - Acute Kidney Injury Following Cardiopulmonary Bypass in Children - Risk Factors
      and Outcomes.
AB  - BACKGROUND: Acute kidney injury (AKI) is the most common and most serious
      complication following heart surgery. We aimed to determine the prevalence of,
      and risk factors for, AKI following pediatric cardiac surgery.Methods and
      Results:We retrospectively analyzed 135 patients aged <=18 years who underwent
      cardiac surgery for congenital heart defects; by RACHS-1 category, 58 patients
      (43%) had an operative risk score >=3. AKI was defined and classified using the
      pediatric pRIFLE criteria (Pediatric Risk, Injury, Failure, Loss, and End-stage
      Kidney Disease); 19 patients (14.1%) developed AKI: 17 had AKI with a severity
      classified as risk (R) and 2 had AKI classified as injury (I). Body weight,
      height, body surface area, and preoperative mechanical ventilation were all
      independently associated with AKI development (P=0.038, 0.040, 0.033 and 0.008,
      respectively). Preoperative ventilation strongly correlated with AKI severity.
      Higher pRIFLE classification positively correlated with increased incidence of
      peritoneal dialysis, increased postoperative mechanical ventilation duration, and
      longer hospital stay (P=0.009, 0.039 and 0.042, respectively). CONCLUSIONS: In
      this study, we found a low prevalence of postoperative AKI in pediatric patients
      undergoing severe cardiac surgery. AKI was associated with worse early
      postoperative outcomes. Early prediction and appropriate treatment of AKI during
      the postoperative period are emphasized.

PMID- 28515371
TI  - Bilateral cervical ribs in a mixed breed dog.
AB  - A 4-year-old intact female, mixed breed dog was presented with a complaint of
      dyspnea. Clinical examination revealed symptoms related to disease of the upper
      airways. Radiographic findings were consistent with tracheal collapse associated
      with anomalies involving the seventh cervical vertebra and the first ribs
      bilaterally. Radiographs were highly suggestive of cervical ribs; computed
      tomography and ultrasound examination allowed complete characterization and
      better localization of the anomalies with relationship to the adjacent muscle and
      vasculature. Cervical ribs are malformations widely described in human medicine,
      but only sporadically in dogs. Herein, we discuss etiological, clinical,
      diagnostic and therapeutic aspects of cervical ribs and possible correlations
      between the cervical ribs and other anatomical anomalies noted in this dog.

PMID- 28515372
TI  - Spinal Arteriovenous Shunts: Angioarchitecture and Historical Changes in
      Classification.
AB  - The purposes of this study were to review historical changes in the
      classification of spinal arteriovenous (AV) shunts and to propose a practical
      classification system. The associated literature regarding the classification of
      spinal AV shunts was reviewed in the angiography era between 1967 and 2015. The
      classification systems of spinal AV shunts and a proposed classification system
      were presented with neuroradiological imaging and medical illustrations. There
      have been seven major classification systems based on the evolution of diagnostic
      methods as well as treatments for spinal AV shunts: the first description of
      spinal AV shunts diagnosed and classified using spinal angiography in 1971; the
      second classification based on a case report of intradural direct perimedullary
      arteriovenous fistulas (AVFs) treated by microsurgery in 1987; the third
      classification based on a case series of intradural perimedullary AVFs treated by
      endovascular interventions in 1993; the fourth and fifth classification systems
      based on a case series of spinal AVFs and arteriovenous malformations (AVMs)
      treated by microsurgery or endovascular interventions in 2002; the sixth
      classification based on a case series of cranio-spinal dural AV shunts in 2009;
      and the seventh classification based on a case series of extradural AVFs treated
      by microsurgery and endovascular interventions in 2011. Based on historical
      reports, the author proposed a classification system according to the sites
      (dural, intradural, and extradural) and types (AVF and AVM) of AV shunts. By
      learning the historical background, we may obtain a clearer understanding of the
      complex and confusing classification system of spinal AV shunts.

PMID- 28515373
TI  - How accurately does the Brief Job Stress Questionnaire identify workers with or
      without potential psychological distress?
AB  - OBJECTIVES: The manual for the Japanese Stress Check Program recommends use of
      the Brief Job Stress Questionnaire (BJSQ) from among the program's instruments
      and proposes criteria for defining "high-stress" workers. This study aimed to
      examine how accurately the BJSQ identifies workers with or without potential
      psychological distress. METHODS: We used an online survey to administer the BJSQ
      with a psychological distress scale (K6) to randomly selected workers (n=1,650).
      We conducted receiver operating characteristics curve analyses to estimate the
      screening performance of the cutoff points that the Stress Check Program manual
      recommends for the BJSQ. RESULTS: Prevalence of workers with potential
      psychological distress defined as K6 score >=13 was 13%. Prevalence of "high
      risk" workers defined using criteria recommended by the program manual was 16.7%
      for the original version of the BJSQ. The estimated values were as follows:
      sensitivity, 60.5%; specificity, 88.9%; Youden index, 0.504; positive predictive
      value, 47.3%; negative predictive value, 93.8%; positive likelihood ratio, 6.0;
      and negative likelihood ratio, 0.4. Analyses based on the simplified BJSQ
      indicated lower sensitivity compared with the original version, although we
      expected roughly the same screening performance for the best scenario using the
      original version. CONCLUSIONS: Our analyses in which psychological distress
      measured by K6 was set as the target condition indicate less than half of the
      identified "high-stress" workers warrant consideration for secondary screening
      for psychological distress.

PMID- 28515374
TI  - Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer
      Cells via IL-6/STAT3 Pathway Inhibition.
AB  - Acquired resistance to epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs) is the most important limiting factor for treatment
      efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has
      linked the epithelial-mesenchymal transition (EMT) to the emergence of drug
      resistance, consequently, ongoing research has been focused on exploring the
      therapeutic options to reverse EMT for delaying or preventing drug resistance.
      Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes
      and displayed anti-cancer properties. In the current work, we aimed to testify
      whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We
      exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired
      resistance with strong features of EMT. PPI effectively restored drug sensitivity
      of cells that obtained acquired resistance. PPI reversed EMT and decreased
      interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3)
      signaling pathway activation in erlotinib-resistant cells. Moreover, addition of
      IL-6 partially abolished the sensitization response of PPI. Furthermore, co
      treatment of erlotinib and PPI completed abrogation of tumor growth in
      xenografts, which was associated with EMT reversal. In conclusion, PPI serves as
      a novel solution to conquer the EGFR-TKI resistance of NSCLC via reversing EMT by
      modulating IL-6/STAT3 signaling pathway. Combined PPI and erlotinib treatment
      provides a promising future for lung cancer patients to strengthen drug response
      and prolong survival.

PMID- 28515376
TI  - Carotenoids of Red, Brown, and Black Specimens of Plectropomus leopardus, the
      Coral Trout (Suziara in Japanese).
AB  - This study investigated the carotenoids occurring in the integument of
      Plectropomus leopardus, the coral trout. For a red specimen, the major
      carotenoids included astaxanthin diester and monoester, as well as alpha
      cryptoxanthin ester, tunaxanthin diester, adonixanthin diester, adonirubin ester,
      and adonirubin; for brown and black specimens, tunaxanthin diester was the main
      carotenoid. 1H-NMR and MS spectral analyses showed that docosahexaenoic acid was
      the sole fatty acid esterified with xanthophylls in the coral trout.

PMID- 28515375
TI  - Modified Gas Chromatographic Method to Determine Monoacylglycerol and
      Diacylglycerol Contents in Edible Fats and Oils.
AB  - Monoacylglycerol (MAG) and diacylglycerol (DAG) are minor components of edible
      fats and oils, and they relate to the quality of these foods. The AOCS official
      method Cd 11b-91 has been used to determine MAG and DAG contents in fats and
      oils. There are, however, difficulties in the determination of MAG and DAG using
      this analytical procedure. Therefore, we improved this method by modifying the
      trimethylsilyl derivatization procedure and replacing the internal standard (IS)
      material. In our modified method, TMS-HT (mixture of hexamethyldisilazane and
      trimethylchlorosilane) was used for derivatization of MAG and DAG, which was
      followed by liquid-liquid extraction with water and n-hexane solution containing
      the IS, tricaprin. Using the modified method, we demonstrated superior
      repeatability in comparison with that of the AOCS method by reducing procedural
      difficulties. The relative standard deviation of distearin peak areas was 1.8% or
      2.9% in the modified method, while it was 5.6% in the AOCS method. In addition,
      capillary columns, such as DB-1ht and DB-5ht could be used in this method.

PMID- 28515377
TI  - High-fat Diet Increases Phospholipid Peroxidation in the Liver of Mature Fischer
      344 Rats.
AB  - Phospholipid peroxidation is considered to be involved in the pathophysiology of
      various diseases. While dietary antioxidants are believed to help prevent these
      diseases via inhibition of phospholipid peroxidation, further evaluation is
      needed to prove this hypothesis. For this, it is crucial to establish an animal
      model with accelerated phospholipid peroxidation. In this study, we hypothesized
      that a combination of aging and high-fat diet feeding may accelerate phospholipid
      peroxidation in vivo. High-fat diets were fed to mature and juvenile Fischer 344
      rats for 12 weeks. The mature rats in particular accumulated body fat and liver
      phosphatidylcholine hydroperoxide (PCOOH). Interestingly, the increase in PCOOH
      levels was abrogated by the co-administration of antioxidants to mature rats.
      This may be attributed to factors including the decrease in body fat, functions
      of vitamin E, and/or the involvement of antioxidant-related genes, each caused by
      antioxidant administration. These results indicate that the high-fat diet-fed
      aging animal model may be suitable for investigation of the relationship between
      phospholipid peroxidation, oxidative stress-related diseases, and dietary
      antioxidants.

PMID- 28515378
TI  - Direct Involvement of Arachidonic Acid in the Development of Ear Edema via TRPV3.
AB  - Arachidonic acid (AA) plays a pivotal role in the development of edema via its
      oxidized metabolites derived from cyclooxygenase (COX) and lipoxygenase (LOX),
      and is recently recognized as an activator of TRPV3. However, it is not clear
      whether AA plays some TRPV3-mediated pathological roles in the development of
      edema. Pharmacological and histological studies using ICRTRPV3+/+ and ICRTRPV3-/-
      mice indicated that higher ear edema responses to topical application of AA were
      observed in ICRTRPV3+/+ mice compared with ICRTRPV3-/- mice. However, there was
      no difference in the ear edema response to 12-O-tetradecanoylphorbol 13-acetate,
      skin histology, and skin barrier function between these mouse strains.
      Furthermore, oxidized fatty acids from the lesional site were analyzed to
      elucidate the TRPV3-mediated pathological roles of AA, and the results revealed
      that there were no differences in the level of COX or LOX metabolites derived
      from AA between both mouse strains. We concluded that AA plays a role in the
      development of TRPV3-mediated ear edema and that this result may contribute to
      better understanding of the pathophysiological mechanisms involved in the
      development of a certain type of edema.

PMID- 28515379
TI  - Alternative Internal Standard Calibration of an Indirect Enzymatic Analytical
      Method for 2-MCPD Fatty Acid Esters.
AB  - An indirect enzymatic analysis method for the quantification of fatty acid esters
      of 2-/3-monochloro-1,2-propanediol (2/3-MCPD) and glycidol was developed, using
      the deuterated internal standard of each free-form component. A statistical
      method for calibration and quantification of 2-MCPD-d5, which is difficult to
      obtain, is substituted by 3-MCPD-d5 used for calculation of 3-MCPD. Using data
      from a previous collaborative study, the current method for the determination of
      2-MCPD content using 2-MCPD-d5 was compared to three alternative new methods
      using 3-MCPD-d5. The regression analysis showed that the alternative methods were
      unbiased compared to the current method. The relative standard deviation (RSDR)
      among the testing laboratories was <= 15% and the Horwitz ratio was <= 1.0, a
      satisfactory value.

PMID- 28515380
TI  - Highly Selective and Considerable Subcritical Butane Extraction to Separate
      Abamectin in Green Tea.
AB  - We specially carried out the subcritical butane extraction to separate abamectin
      from tea leaves. Four parameters, such as extraction temperature, extraction
      time, number of extraction cycles, and solid-liquid ratio were studied and
      optimized through the response surface methodology with design matrix developed
      by Box-Behnken. Seventeen experiments with three various factors and three
      variable levels were employed to investigate the effect of these parameters on
      the extraction of abamectin. Besides, catechins, theanine, caffeine, and aroma
      components were determined by both high-performance liquid chromatography and gas
      chromatography-mass spectrometry to evaluate the tea quality before and after the
      extraction. The results showed that the extraction temperature was the uppermost
      parameter compared with others. The optimal extraction conditions selected as
      follows: extraction temperature, 42 degrees C; number of extraction cycles and
      extraction time, 1 and 30 min, respectively; and solid-liquid ratio, 1:10. Based
      on the above study, the separation efficiency of abamectin was up to 93.95%. It
      is notable that there has a quite low loss rate, including the negligible damage
      of aroma components, the bits reduce of catechins within the range of 0.7%-13.1%,
      and a handful lessen of caffeine and theanine of 1.81% and 2.6%, respectively.
      The proposed method suggested subcritical butane possesses solubility for lipid
      soluble pesticides, and since most of the pesticides are attached to the surfaces
      of tea, thus the as-applied method was successfully effective to separate
      abamectin because of the so practical and promising method.

PMID- 28515381
TI  - Preliminary Evaluation of Glyceric Acid-producing Ability of Acidomonas
      methanolica NBRC104435 from Glycerol Containing Methanol.
AB  - Some acetic acid bacteria produce large amounts of glyceric acid (GA) from
      glycerol in culture broth. However, methanol, which is a major contaminant of raw
      glycerol derived from the biodiesel fuel industry, sharply decreases cell growth
      and GA production [AMB Express, 3, 20, 2013]. Thus, we evaluated the
      methylotrophic acetic acid bacterium Acidomonas methanolica NBRC104435 for its
      ability to produce GA from glycerol containing methanol. This strain accumulated
      GA in its culture broth when 1-3 wt% glycerol was available as a carbon source.
      We observed improved cell growth and GA accumulation when 1 vol% methanol was
      added to the 3-5 wt% glycerol medium. The maximum concentration of GA was 12.8
      g/L in medium containing 3 wt% glycerol plus 1 vol% methanol. In addition, the
      enantiomeric excess (ee) of the GA produced was revealed to be 44%, indicating
      that this strain converted glycerol to d-GA with a lower enantioselectivity than
      other acetic acid bacteria, which had 70-99% ee.

PMID- 28515382
TI  - Screening Evaluation of the Interaction of Linear-Chain or Branched-Chain
      Peptides with Multilamellar Vesicle, Using Confocal Laser Microscopy.
AB  - In the present research, we prepared an acidic liposome as a cell model and used
      confocal laser microscopy to evaluate its interaction with oligopeptides that had
      high membrane permeability or affinity. The results showed that, for short
      peptides of about ten residues, the positive charge peptides interacted with the
      acidic liposome strongly. For peptides that interacted with the liposome, no
      difference was found between linear-chain and branched-chain peptides due to
      their structure.

PMID- 28515383
TI  - A New Agonist for Peroxisome Proliferation-activated Receptor gamma (PPARgamma),
      Fraglide-1 from Zhenjiang Fragrant Vinegar: Screening and Characterization Based
      on Cell Culture Experiments.
AB  - Zhenjiang fragrant vinegar (Kozu) is a black rice vinegar that has been used as a
      traditional Chinese medicine and has various health benefits, including anti
      obesity effects. In the present study, using luciferase reporter assays of
      PPARgamma promoter activity, a novel ingredient from 8-year-old Kozu, 5-hydroxy-4
      phenyl-butenolide, was isolated. The newly found agonist was named as "Fraglide
      1". Moreover, in subsequent experiments, it was confirmed that fraglide-1 was an
      PPARgamma agonist and it could increase expression level of the uncoupling
      protein (UCP)-1. Fraglide-1 was chemically synthesized and it was verified that
      expression of the PPARgamma was increased in dose dependent manner. Although Kozu
      has been consumed globally as a functional food for thousands of years, the
      mechanisms behind its health effects have not been characterized. The active
      ingredient of Kozu was successfully found and the results unraveled a longtime
      mystery about Kozu for its beneficial health effect.

PMID- 28515384
TI  - Physicochemical and Antioxidant Properties of Rice Bran Oils Produced from
      Colored Rice Using Different Extraction Methods.
AB  - This study investigated the physicochemical and antioxidant properties of rice
      bran oil (RBO) produced from the bran of three rice varities; Khao Dawk Mali 105
      (white rice), Red Jasmine rice (red rice) and Hom-nin rice (black rice) using
      three extraction methods including cold-press extraction (CPE), solvent
      extraction (SE) and supercritical CO2 extraction (SC-CO2). Yields, color, acid
      value (AV), free fatty acid (FFA), peroxide value (PV), iodine value (IV), total
      phenolic compound (TPC), gamma-oryzanol, alpha-tocopherol and fatty acid profile
      were analyzed. It was found that the yields obtained from SE, SC-CO2 and CPE
      extractions were 17.35-20.19%, 14.76-18.16% and 3.22-6.22%, respectively. The RBO
      from the bran of red and black rice samples exhibited high antioxidant
      activities. They also contained higher amount of gamma-oryzanol and alpha
      tocopherol than those of white rice sample. In terms of extraction methods, SC
      CO2 provided better qualities of RBO as evidenced by their physicochemical and
      antioxidant properties. This study found that RBO produced from the bran of black
      rice samples using SC-CO2 extraction method showed the best physicochemical and
      antioxidant properties.

PMID- 28515385
TI  - Supercritical CO2 Extraction of Rice Bran Oil -the Technology, Manufacture, and
      Applications.
AB  - Rice bran is a good source of nutrients that have large amounts of phytochemicals
      and antioxidants. Conventional rice bran oil production requires many processes
      that may deteriorate and degrade these valuable substances. Supercritical CO2
      extraction is a green alternative method for producing rice bran oil. This work
      reviews production of rice bran oil by supercritical carbon dioxide (SC-CO2)
      extraction. In addition, the usefulness and advantages of SC-CO2 extracted rice
      bran oil for edible oil and health purpose is also described.

PMID- 28515386
TI  - Autoxidation of Fish Oil Blended with Rice Bran Oil.
AB  - Effects of rice bran oil on the oxidative and flavor stability of fish oil were
      investigated by the gas liquid chromatography-head space method. When fish oil
      blending with different ratio of rice bran oils was oxidized at room temperature
      in the dark, volatile compounds produced during autoxidation was measured by gas
      liquid chromatography. The amounts of volatile compounds were decreased with
      increased the ratio of blended rice bran oil as well as peroxide value. The level
      of propanal and acrolein which gave unpleasant flavor was also decreased with
      increased the ratio of blended rice bran oil. Especially, the level of propanal
      and acrolein and peroxide value were remarkably decreased when blending more than
      75% of rice bran oil. Blending of rice bran oil improved the oxidative and flavor
      stabilities of fish oil.

PMID- 28515387
TI  - Functional polymorphisms affecting Th1 differentiation are associated with the
      severity of autoimmune thyroid diseases.
AB  - The prognosis for autoimmune thyroid diseases (AITDs), such as Hashimoto's
      disease (HD) and Graves' disease (GD), varies among patients. Interleukin (IL)-12
      and IL-18 also induce Th1 differentiation, and SOCS1 (Suppressor of cytokine
      signaling 1) and TIM-3 (T cell immunoglobulin and mucin domain-3) are known to be
      negative regulators of Th1 cells. To clarify the association of functional
      polymorphisms in the IL12, IL12Rbeta1, IL18, SOCS1 and TIM3 genes with the
      intractability and severity of autoimmune thyroid disease (AITD), we genotyped
      these polymorphisms in 151 GD patients, including 61 patients with intractable GD
      and 51 patients with GD in remission, in 140 HD patients, including 59 patients
      with severe HD and 55 patients with mild HD, and in 74 healthy controls. The
      frequency of the IL18 -607CC genotype which correlates with a high production of
      IL-18, was significantly higher in patients with GD in remission than in those
      with intractable GD (p=0.0178). The -607C allele was significantly higher in
      patients with severe HD than in those with mild HD (p=0.0050). The -607CC
      genotype in IL18 gene may be protective against the intractability of GD, and the
      -607C allele may enhance the severity of HD.

PMID- 28515388
TI  - Nitric oxide is critical for avoiding hepatic lipid overloading via IL-6
      induction during liver regeneration after partial hepatectomy in mice.
AB  - Nitric oxide (NO), generated from L-arginine by three different isoforms of
      nitric oxide synthase (NOS), is a pleiotropic factor to regulate physiological
      functions in almost every organ and tissue. Each knockout mouse of iNOS or eNOS
      has been used to suggest that NO has a crucial role in liver regeneration after
      partial hepatectomy (PH), for NO may inhibit caspase 3 activity and is required
      for EGFR signaling. In previous reports, defective mitochondrial beta-oxidation
      was observed in eNOS KO mice, and hepatic steatosis was often correlated to
      deficient liver regeneration, so we focused on metabolic perspective and
      hypothesized that NO depletion in PH mice would affect hepatocytic lipolysis and
      impair hepatocytes proliferation. We inhibited all NOS isoforms by administrating
      L-NG-nitroarginine methyl ester (L-NAME) to PH mice, and hepatocyte DNA synthesis
      was severely inhibited at 40-44 h post PH in L-NAME (+) group. IL-6 was robustly
      secreted into circulating blood in L-NAME (-) group, but not in L-NAME (+) group.
      Down-regulation of carnitine palmytoyltransferase 1A, massive lipid accumulation
      and elevated endoplasmic reticulum (ER) stress relative genes expression level
      were observed in L-NAME (+) group mouse liver. The expression level of C/EBP
      homologous protein, a mediator of ER stress induced apoptosis, significantly
      increased in L-NAME (+) group. Our findings suggest the lack of NO affected IL-6
      induction and hepatocyte lipolysis after PH, consequently leading to excessive
      hepatic lipid accumulation, elevated ER stress and impaired hepatocyte
      proliferation.

PMID- 28515389
TI  - Ca2+ in Hybridization Solutions for Fluorescence in situ Hybridization
      Facilitates the Detection of Enterobacteriaceae.
AB  - Fluorescence in situ hybridization (FISH) has been employed to identify
      microorganisms at the single cell level under a microscope. Extensive efforts
      have been made to improve and extend the FISH technique; however, the development
      of a widely applicable protocol is a continuing challenge. The present study
      evaluated the effects of divalent cations in the hybridization solution on the
      FISH-based detection of various species of bacteria and archaea with rRNA
      targeted probes. A flow cytometric analysis after FISH with a standard
      hybridization buffer detected positive signals from less than 30% of Escherichia
      coli IAM 1264 cells. However, the number of cells with positive signals increased
      to more than 90% after the addition of calcium chloride to the hybridization
      buffer. Mn2+ also had positive effects, whereas Mg2+ did not. The positive
      effects of Ca2+ were similarly observed for bacteria belonging to
      Enterobacteriaceae, including Enterobacter sakazakii IAM 12660T, E. aerogenes IAM
      12348, Klebsiella planticola IAM 14202, and Salmonella enterica subsp. enterica
      serovar Typhimurium strain LT2. These results indicate that the supplementation
      of Ca2+ to the hybridization buffer for FISH contributes to the efficient
      detection of Enterobacteriaceae cells.

PMID- 28515390
TI  - Biocontrol Potential of an Endophytic Streptomyces sp. Strain MBCN152-1 against
      Alternaria brassicicola on Cabbage Plug Seedlings.
AB  - In the present study, 77 strains of endophytic actinomycetes isolated from
      cabbage were screened in order to assess their biocontrol potential against
      Alternaria brassicicola on cabbage seedlings. In the first and second screening
      trials, cabbage seedlings pretreated with mycelial suspensions of each isolate
      were spray-inoculated with A. brassicicola. Strain MBCN152-1, which exhibited the
      best protection in screening trials and had no adverse effects on seedling
      growth, was selected for the greenhouse trial. In the greenhouse trial, cabbage
      seedlings, which had been grown in plug trays filled with soil mix containing
      spores of MBCN152-1 (1*108 spores g-1 of soil mix), were spray-inoculated with A.
      brassicicola and grown in greenhouse conditions. MBCN152-1 reduced disease
      incidence and significantly increased the number of viable seedlings. The
      efficacy of MBCN152-1 against damping-off caused by seed-borne A. brassicicola
      was then evaluated. Cabbage seeds, artificially infested with A. brassicicola,
      were sown in soil mix containing MBCN152-1 spores. The disease was completely
      suppressed when infested seeds were sown in a soil mix blended with MBCN152-1 at
      1.5*107 spores g-1 of soil mix. These results strongly suggest that MBCN152-1 has
      the potential to control A. brassicicola on cabbage plug seedlings. MBCN152-1 was
      identified as a Streptomyces humidus-related species based on 16S rDNA
      sequencing. Scanning electron microscopy showed that the hyphae of MBCN152-1
      multiplied on the surface of the seedlings and penetrated their epidermal cells.
      In conclusion, strain MBCN152-1 is a promising biocontrol agent against A.
      brassicicola on cabbage plug seedlings.

PMID- 28515392
TI  - Assessment of Left Ventricular Function and Mass on Free-Breathing Compressed
      Sensing Real-Time Cine Imaging.
AB  - BACKGROUND: Compressed sensing (CS) cine magnetic resonance imaging (MRI) has the
      advantage of being inherently insensitive to respiratory motion. This study
      compared the accuracy of free-breathing (FB) CS and breath-hold (BH) standard
      cine MRI for left ventricular (LV) volume assessment.Methods and Results:Sixty
      three patients underwent cine MRI with both techniques. Both types of images were
      acquired in stacks of 8 short-axis slices (temporal/spatial resolution, 41
      ms/1.7*1.7*6 mm3) and compared for ejection fraction, end-diastolic and systolic
      volumes, stroke volume, and LV mass. Both BH standard and FB CS cine MRI provided
      acceptable image quality for LV volumetric analysis (score >=3) in all patients
      (4.7+/-0.5 and 3.7+/-0.5, respectively; P<0.0001) and had good agreement on LV
      functional assessment. LV mass, however, was slightly underestimated on FB CS
      cine MRI (median, IQR: BH standard, 83.8 mL, 64.7-102.7 mL; FB CS, 79.0 mL, 66.0
      101.0 mL; P=0.0006). The total acquisition times for BH standard and FB CS cine
      MRI were 113+/-7 s and 24+/-4 s, respectively (P<0.0001). CONCLUSIONS: Despite
      underestimation of LV mass, FB CS cine MRI is a clinically useful alternative to
      BH standard cine MRI in patients with impaired BH capacity.

PMID- 28515391
TI  - Advanced glycation end products regulate interleukin-1beta production in human
      placenta.
AB  - Maternal obesity is a major risk factor for pregnancy complications, causing
      inflammatory cytokine release in the placenta, including interleukin-1beta (IL
      1beta), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic
      and placental inflammation with elevated circulating advanced glycation end
      products (AGEs). IL-1beta is a pivotal inflammatory cytokine associated with
      obesity and pregnancy complications, and its production is regulated by NLR
      family pyrin domain-containing 3 (NLRP3) inflammasomes. Here, we investigated
      whether AGEs are involved in the activation of NLRP3 inflammasomes using human
      placental tissues and placental cell line. In human placental tissue cultures,
      AGEs significantly increased IL-1beta secretion, as well as IL-1beta and NLRP3
      mRNA expression. In human placental cell culture, although AGE treatment did not
      stimulate IL-1beta secretion, AGEs significantly increased IL-1beta mRNA
      expression and intracellular IL-1beta production. After pre-incubation with AGEs,
      nano-silica treatment (well known as an inflammasome activator) increased IL
      1beta secretion in placental cells. However, after pre-incubation with
      lipopolysaccharide to produce pro-IL-1beta, AGE treatment did not affect IL-1beta
      secretion in placental cells. These findings suggest that AGEs stimulate pro-IL
      1beta production within placental cells, but do not activate inflammasomes to
      stimulate IL-1beta secretion. Furthermore, using pharmacological inhibitors, we
      demonstrated that AGE-induced inflammatory cytokines are dependent on MAPK/NF
      kappaB/AP-1 signaling and reactive oxygen species production in placental cells.
      In conclusion, AGEs regulate pro-IL-1beta production and inflammatory responses,
      resulting in the activation of NLRP3 inflammasomes in human placenta. These
      results suggest that AGEs, as an endogenous and sterile danger signal, may
      contribute to chronic placental cytokine production.

PMID- 28515394
TI  - CROSS-TALK BETWEEN IMMUNE SYSTEM AND BRAIN.

PMID- 28515393
TI  - PHENOTYPE OF ALLERGIC RHINITIS AND RHINOSINUSITIS.

PMID- 28515395
TI  - THE INTERRELATIONSHIP BETWEEN ASTHMA AND BRAIN ACTIVITIES: PSYCHOLOGICAL STRESS
      RELATED ASTHMA AS A NEW ASTHMA PHENOTYPE.

PMID- 28515396
TI  - JAPANESE GUIDELINE FOR OCCUPATIONAL ALLERGIC DISEASES 2016.

PMID- 28515397
TI  - AIRWAY INFLAMMATION IN ASTHMA.

PMID- 28515398
TI  - EXPERIMENTAL EVIDENCES FOR LOCAL ALLERGIC RHINITIS.

PMID- 28515399
TI  - CROSS TALK OF INNATE AND ACQUIRED IMMUNITY IN ALLERGY.

PMID- 28515400
TI  - THE ROLE OF MyD88 SIGNALING IN IgE RESPONSES IN LUNGS.

PMID- 28515401
TI  - BASIC ACT ON ALLERGIC DISEASES MEASURES AND EQUALIZATION OF MEDICAL CARE IN
      ALLERGIC DISEASES THROUGHOUT THE JAPAN.

PMID- 28515402
TI  - DIFFERENCES IN FRACTION OF EXHALED NITRIC OXIDE VALUES MEASURED BY TWO HAND
      HELDED ANALYZERS (NObreath(r) AND NIOX Vero(r)).
AB  - BACKGROUND: The fraction of exhaled nitric oxide (FENO) is a useful marker of
      asthma control. The FENO measurement with two hand-helded analyzers (NObreath(r)
      and NIOX Vero(r)) may be more affordable, no studies have examined the
      differences in FENO values measured with those methods in adult. METHODS: The
      study population comprised 44 subjects at our outpatient clinic. FeNO values
      (FENOb and FENOv) were measured by two methods (NObreath(r) and NIOX Vero(r)).
      RESULTS: FENOb values were significantly correlated with FENOv (r = 0.911, p <
      0.001). However, FENOv values were high compared with FENOb (FENOv = 1.40 *
      FENOb). CONCLUSION: Differences exist in the values of FENO measured by two hand
      helded analyzers: conversion equations are needed to compare the FENO values
      between these methods.

PMID- 28515403
TI  - ANALYSIS OF WHEAT ALLERGEN DISPERSED IN AIR BY THE ACTION OF THREE TYPES OF FLOUR
      SIFTER.
AB  - BACKGROUND: Since wheat flour, a cause of food allergy, tends to disperse rapidly
      in air, it can unintentionally mix other foods during the sieving process. Our
      aim was to analyze the dispersal of wheat flour dust in air in order to prevent
      unintentional mixing. METHODS: We measured particle size distribution of wheat
      flour, photographed the scattered flour for 60 seconds every 10 seconds after
      sieving through three types of flour sifter, constructed a velocity vector
      diagram of flour dust dispersal by each type of sifter, and measured the distance
      of wheat allergen dispersal over 20 minutes using a petri dish and
      immunochromatographic test. RESULTS: The particles were mainly 14.2MUm and
      60.4MUm in diameter and settled at terminal velocities of about 8mm/s and
      150mm/s, respectively. Wheat flour particles of more than 60MUm (released in air
      by sifting) dropped mainly in the perpendicular direction, while particles of
      less than 30MUm remained suspended and traveled 5m after sifting by all flour
      sifters. CONCLUSION: Our results suggested that wheat flour dust dispersed by
      sifting (regardless of sifter) could unintentionally mix other foods. To prevent
      contamination, it is necessary to control the flow of air or sift flour in a
      separate room.

PMID- 28515404
TI  - INSOLUBILITY AND ALTERATION OF ALLERGENIC ACTIVITY OF WHEAT PROTEINS IN PROCESSED
      FOODS.
AB  - BACKGROUND: Food processing causes decomposition, denaturation or polymerization
      of protein, which may alter an allergic reaction. This study aimed to investigate
      the insolubility and alteration of wheat allergens in processed foods and the
      reactivity to patient sera. METHODS: We extracted proteins from wheat flour, udon
      and bread using different extracts and conducted SDS-polyacrylamide gel
      electrophoresis. IgE-immunoblotting was also conducted using sera from children
      with wheat allergy. RESULTS: Soluble protein was extracted from wheat flour, and
      gluten fractions were also extracted by adding SDS. However, no proteins were
      able to be extracted from udon or bread witout severing the disulfide bonds under
      reducing condition. Only trace amounts of protein were detected in the water
      after boiling udon noodles. The reactivity of IgE antibody to the extracted
      protein did not differ among the different processed food types. CONCLUSIONS:
      Wheat allergens became strongly insolubilized after gluten formation and heating.
      However, the reactivity of IgE antibody to each allergen was not affected by food
      processing. Further studies are needed for the effects on clinical symptoms.

PMID- 28515406
TI  - Innate lymphoid cell (ILC) 3.

PMID- 28515405
TI  - A CASE OF BRONCHIAL ASTHMA WITH HYPEREOSINOPHILIA WITH EFFECTIVE SAIBOKUTOU
      THERAPY.
AB  - A 42 year old woman visited on our hospital because of cough, sputum, pruritus
      and erythema. She showed peripheral blood eosinophilia, high level of FENO,
      bronchial hyperresponsiveness. Diagnosis of bronchial asthma and atopic
      dermatitis was made, but she rejected therapy except for Saibokutou, a Kampo
      herbal medicine. After 1 year, her symptoms and her laboratory data were
      improved.

PMID- 28515408
TI  - Variable Distribution of Pseudolobules in Ovarian Sclerosing Stromal Tumors:
      Utility of Diffusion-weighted Imaging for Differential Diagnosis.

PMID- 28515407
TI  - Comparison of the OUTBACK(r) Elite Reentry Catheter and the Bi-directional
      Approach after Failed Antegrade Approach for Femoro-popliteal Occlusive Disease.
AB  - AIM: A successful antegrade wire crossing for femoro-popliteal chronic total
      occlusion (FP-CTO) is still a technical challenge. We attempted to demonstrate
      the safety and feasibility of the OUTBACK(r) Elite reentry catheter and the bi
      directional approach for failed FP-CTO cases with the antegrade approach.
      METHODS: Endovascular therapy for FP-CTO was performed in 219 lesions from May
      2013 to December 2016 at Morinomiya Hospital. We retrospectively analyzed the
      data of 43 consecutive lesions which underwent endovascular therapy using the bi
      directional approach with distal access and the mono-directional approach with
      the OUTBACK(r) Elite reentry catheter for FP-CTO lesions. The antegrade success
      using a combination of traditional and Intravascular Ultrasound (IVUS) -guided
      techniques was achieved in 170 lesions out of a total of 219 lesions. From May
      2013 to June 2016 (phase 1), the bi-directional approach with distal access was
      applied to 22 lesions after failed antegrade approaches. From July 2016 to
      December 2016 (phase 2), the mono-directional approach with the OUTBACK(r) Elite
      reentry catheter was applied to 21 lesions. RESULTS: Clinical and lesion
      characteristics in phase 1 were not significantly different from those in phase
      2. The overall initial technical success rate was 100% in both phases. The total
      wire number and amount of contrast media were significantly less, and the total
      procedure time and the total fluoroscopic time were significantly shorter in
      phase 2 than in phase 1 (p<0.01). CONCLUSIONS: Endovascular therapy for FP-CTO
      using the OUTBACK(r) Elite reentry catheter is feasible and safe after a failed
      antegrade approach.

PMID- 28515409
TI  - Saturation Recovery Myocardial T1 Mapping with a Composite Radiofrequency Pulse
      on a 3T MR Imaging System.
AB  - PURPOSE: To evaluate the effect of a composite radiofrequency (RF) pulse on
      saturation recovery (SR) myocardial T1 mapping using a 3T MR system. MATERIALS
      AND METHODS: Phantom and in vivo studies were performed with a clinical 3T MR
      scanner. Accuracy and reproducibility of the SR T1 mapping using conventional and
      composite RF pulses were first compared in phantom experiments. An in vivo study
      was performed of 10 healthy volunteers who were imaged with conventional and
      composite RF pulse methods twice each. In vivo reproducibility of myocardial T1
      value and the inter-segment variability were assessed. RESULTS: The phantom study
      revealed significant differences in the mean T1 values between the two methods,
      and the reproducibility for the composite RF pulse was significantly smaller than
      that for the conventional RF pulse. For both methods, the correlations of the
      reference and measured T1 values were excellent (r2 = 0.97 and 0.98 for
      conventional and composite RF pulses, respectively). The in vivo study showed
      that the mean T1 value for composite RF pulse was slightly lower than that for
      conventional RF pulse, but this difference was not significant (P = 0.06). The
      inter-segment variability for the composite RF pulse was significantly smaller
      than that for conventional RF pulse (P < 0.01). Inter-scan correlations of T1
      measurements of the first and second scans were highly and weakly correlated to
      composite RF pulses (r = 0.83 and 0.29, respectively). CONCLUSION: SR T1 mapping
      using composite RF pulse provides accurate quantification of T1 values and can
      lessen measurement variability and enable reproducible T1 measurements.

PMID- 28515410
TI  - Differentiating between Central Nervous System Lymphoma and High-grade Glioma
      Using Dynamic Susceptibility Contrast and Dynamic Contrast-enhanced MR Imaging
      with Histogram Analysis.
AB  - PURPOSE: We evaluated the diagnostic performance of histogram analysis of data
      from a combination of dynamic susceptibility contrast (DSC)-MRI and dynamic
      contrast-enhanced (DCE)-MRI for quantitative differentiation between central
      nervous system lymphoma (CNSL) and high-grade glioma (HGG), with the aim of
      identifying useful perfusion parameters as objective radiological markers for
      differentiating between them. METHODS: Eight lesions with CNSLs and 15 with HGGs
      who underwent MRI examination, including DCE and DSC-MRI, were enrolled in our
      retrospective study. DSC-MRI provides a corrected cerebral blood volume (cCBV),
      and DCE-MRI provides a volume transfer coefficient (Ktrans) for transfer from
      plasma to the extravascular extracellular space. Ktrans and cCBV were measured
      from a round region-of-interest in the slice of maximum size on the contrast
      enhanced lesion. The differences in t values between CNSL and HGG for determining
      the most appropriate percentile of Ktrans and cCBV were investigated. The
      differences in Ktrans, cCBV, and Ktrans/cCBV between CNSL and HGG were
      investigated using histogram analysis. Receiver operating characteristic (ROC)
      analysis of Ktrans, cCBV, and Ktrans/cCBV ratio was performed. RESULTS: The 30th
      percentile (C30) in Ktrans and 80th percentile (C80) in cCBV were the most
      appropriate percentiles for distinguishing between CNSL and HGG from the
      differences in t values. CNSL showed significantly lower C80 cCBV, significantly
      higher C30 Ktrans, and significantly higher C30 Ktrans/C80 cCBV than those of
      HGG. In ROC analysis, C30 Ktrans/C80 cCBV had the best discriminative value for
      differentiating between CNSL and HGG as compared to C30 Ktrans or C80 cCBV.
      CONCLUSION: The combination of Ktrans by DCE-MRI and cCBV by DSC-MRI was found to
      reveal the characteristics of vascularity and permeability of a lesion more
      precisely than either Ktrans or cCBV alone. Histogram analysis of these vascular
      microenvironments enabled quantitative differentiation between CNSL and HGG.

PMID- 28515411
TI  - Evaluating Myometrial Invasion in Endometrial Cancer: Comparison of Reduced Field
      of-view Diffusion-weighted Imaging and Dynamic Contrast-enhanced MR Imaging.
AB  - PURPOSE: To compare the diagnostic ability of reduced FOV diffusion-weighted (DW)
      MR imaging with that of 3D dynamic contrast-enhanced (DCE) MR imaging in
      evaluating the depth of myometrial invasion in patients with endometrial cancer.
      METHODS: Three tesla MR images including T2-weighted imaging, reduced FOV DW
      imaging and 3D DCE MR imaging in sagittal and oblique axial (short axis) planes
      in 25 women with surgically proven endometrial cancer were retrospectively
      evaluated. The depth of myometrial invasion (stage S: < 50% vs stage D: >= 50%)
      on MR imaging was correlated with surgical pathology results. RESULTS: The 25
      endometrial cancers included 16 stage S and 9 stage D tumors. The depth of
      myometrial invasion could be accurately evaluated in 68% of the cases for T2
      weighted imaging, 92% for 3D DCE MR imaging, and 96% for reduced FOV DW imaging.
      In two patients with coexisting adenomyosis, both T2-weighted imaging and 3D DCE
      MR imaging failed to reveal the deep myometrial invasion, and reduced FOV DW
      imaging clearly demonstrated the tumor margin in the cases. Combination of
      reduced FOV DW imaging reading together with T2-weighted imaging improved the
      assessment of myometrial invasion with a diagnostic accuracy of up to 100%.
      CONCLUSIONS: Addition of reduced FOV DW imaging may improve the staging accuracy
      of MR imaging for endometrial cancer in assessing the depth of myometrial
      invasion. Especially, reduced FOV DW imaging has an advantage in assessing the
      depth of myometrial invasion for patients with coexisting adenomyosis. Reduced
      FOV DW imaging can be an alternative to 3D DCE MR imaging in evaluating
      myometrial invasion of endometrial cancer without the use of contrast medium.

PMID- 28515412
TI  - Utility of a Hybrid IVIM-DKI Model to Predict the Development of Distant
      Metastasis in Head and Neck Squamous Cell Carcinoma Patients.
AB  - PURPOSE: To evaluate the diagnostic power of hybrid intravoxel incoherent motion
      (IVIM)-diffusion kurtosis imaging (DKI) model parameters in pretreatment for the
      prediction of future distant metastasis in head and neck squamous cell carcinoma
      (HNSCC) patients. MATERIALS AND METHODS: We retrospectively evaluated 49 HNSCC
      patients who underwent curative chemoradiation therapy. Diffusion-weighted image
      (DWI) acquired by single-shot spin-echo echo-planar imaging with 12 b-values (0
      2000) was performed in all patients before any treatment. We calculated the IVIM
      DKI parameters and the conventional apparent diffusion coefficient (ADC) in the
      ROI placed on the primary lesion. The presence of future distant metastasis was
      determined by histological findings or clinical follow-up. RESULTS: A univariate
      analysis revealed significant differences between the patients with distant
      metastasis and those without in slow diffusion coefficient (D) and kurtosis value
      (K). Highest diagnostic accuracy was obtained by the D value. In addition, a
      multivariate analysis revealed that the D value was an independent predictor of
      future distant metastasis. CONCLUSION: The D and K values obtained by this hybrid
      IVIM-DKI model can be one of the diagnostic tools for the prediction of future
      distant metastasis in HNSCC patients.

PMID- 28515414
TI  - Mediastinal Solitary Fibrous Tumor Diagnosed by Endobronchial Ultrasound-Directed
      Biopsy.
AB  - BACKGROUND Solitary fibrous tumors of the middle mediastinal space are uncommon
      and often not discovered until symptoms secondary to compression of adjacent
      structures occur. Diagnosis requires surgical biopsy and histological tissue
      analysis. We describe the ECHO appearance of the solitary fibrous tumor and
      successful non-invasive EBUS diagnosis. This method of diagnosis allowed for
      surgical planning for resection and allowed us to exclude non-surgical diseases,
      such as small cell carcinoma. CASE REPORT A 32-year-old man presented to his
      primary care physician with worsening intermittent chronic chest pain with recent
      progressive dysphagia, cough, and dyspnea. Physical examination and routine
      laboratory work-up were unrevealing. Chest radiograph and computed tomography
      (CT) of the chest revealed a middle mediastinal mass. Flexible bronchoscopy
      confirmed extrinsic compression of right and left bronchial trees. Endobronchial
      ultrasound (EBUS) was used to biopsy the mass and the diagnosis of solitary
      fibrous tumor was confirmed. The patient underwent successful tumor resection and
      was discharged home after an uneventful postoperative period. CONCLUSIONS
      Endobronchial ultrasound-directed tissue biopsy is an appropriate modality for
      suspected solitary fibrous tumors of the mediastinum. To our knowledge, this is
      only the second reported case of SFT diagnosed by EBUS-TBNA. Our case uniquely
      demonstrates the advantages of pre-surgical diagnosis of mediastinal masses with
      EBUS-TBNA when the diagnosis SFT is suggested on CT and US imaging.

PMID- 28515413
TI  - Magnetic Susceptibility Changes in the Basal Ganglia and Brain Stem of Patients
      with Wilson's Disease: Evaluation with Quantitative Susceptibility Mapping.
AB  - OBJECTIVES: Wilson's disease (WD) is characterized with the accumulation of
      copper in the liver and brain. The objective of this study is to quantitatively
      measure the susceptibility changes of basal ganglia and brain stem of pediatric
      patients with neurological WD using quantitative susceptibility mapping (QSM) in
      comparison to healthy controls. METHODS: Eleven patients with neurological WD
      (mean age 15 +/- 3.3 years, range 10-22 years) and 14 agematched controls were
      prospectively recruited. Both groups were scanned on a 1.5 Tesla clinical
      scanner. In addition to T1- and T2-weighted MR images, a 3D multi-echo spoiled
      gradient echo (GRE) sequence was acquired and QSM images were derived offline.
      The quantitative measurement of susceptibility of corpus striatum, thalamus of
      each hemisphere, midbrain, and pons were assessed with the region of interest
      analysis on the QSM images. The susceptibility values for the patient and control
      groups were compared using twosample t-test. RESULTS: One patient with WD had T1
      shortening in the bilateral globus pallidus. Another one had hyperintensity in
      the bilateral putamen, caudate nuclei, and substantia nigra on T2-weighted
      images. The rest of the patients with WD and all subjects of the control group
      had no signal abnormalities on conventional MR images. The susceptibility
      measures of right side of globus pallidus, putamen, thalamus, midbrain, and
      entire pons were significantly different in patients compared to controls (P <
      0.05). CONCLUSION: QSM method exhibits increased susceptibility differences of
      basal ganglia and brain stem in patients with WD that have neurologic impairment
      even if no signal alteration is detected on T1- and T2-weighted MR images.

PMID- 28515416
TI  - Observational Evidence for Desert Amplification Using Multiple Satellite
      Datasets.
AB  - Desert amplification identified in recent studies has large uncertainties due to
      data paucity over remote deserts. Here we present observational evidence using
      multiple satellite-derived datasets that desert amplification is a real large
      scale pattern of warming mode in near surface and low-tropospheric temperatures.
      Trend analyses of three long-term temperature products consistently confirm that
      near-surface warming is generally strongest over the driest climate regions and
      this spatial pattern of warming maximizes near the surface, gradually decays with
      height, and disappears in the upper troposphere. Short-term anomaly analyses show
      a strong spatial and temporal coupling of changes in temperatures, water vapor
      and downward longwave radiation (DLR), indicating that the large increase in DLR
      drives primarily near surface warming and is tightly associated with increasing
      water vapor over deserts. Atmospheric soundings of temperature and water vapor
      anomalies support the results of the long-term temperature trend analysis and
      suggest that desert amplification is due to comparable warming and moistening
      effects of the troposphere. Likely, desert amplification results from the
      strongest water vapor feedbacks near the surface over the driest deserts, where
      the air is very sensitive to changes in water vapor and thus efficient in
      enhancing the longwave greenhouse effect in a warming climate.

PMID- 28515417
TI  - A generalized population dynamics model for reproductive interference with
      absolute density dependence.
AB  - Interspecific mating interactions, or reproductive interference, can affect
      population dynamics, species distribution and abundance. Previous population
      dynamics models have assumed that the impact of frequency-dependent reproductive
      interference depends on the relative abundances of species. However, this
      assumption could be an oversimplification inappropriate for making quantitative
      predictions. Therefore, a more general model to forecast population dynamics in
      the presence of reproductive interference is required. Here we developed a
      population dynamics model to describe the absolute density dependence of
      reproductive interference, which appears likely when encounter rate between
      individuals is important. Our model (i) can produce diverse shapes of isoclines
      depending on parameter values and (ii) predicts weaker reproductive interference
      when absolute density is low. These novel characteristics can create conditions
      where coexistence is stable and independent from the initial conditions. We
      assessed the utility of our model in an empirical study using an experimental
      pair of seed beetle species, Callosobruchus maculatus and Callosobruchus
      chinensis. Reproductive interference became stronger with increasing total beetle
      density even when the frequencies of the two species were kept constant. Our
      model described the effects of absolute density and showed a better fit to the
      empirical data than the existing model overall.

PMID- 28515415
TI  - Evaluation of Mycophenolate Mofetil and Low-Dose Steroid Combined Therapy in
      Moderately Severe Henoch-Schonlein Purpura Nephritis.
AB  - BACKGROUND The most appropriate management of Henoch-Schonlein Purpura (HSP)
      nephritis with nephrotic-range proteinuria remains uncertain. The aim of this
      study was to evaluate the clinical therapeutic effects of mycophenolate mofetil
      and low-dose steroid in Henoch-Schonlein purpura nephritis (HSPN) with nephrotic
      range proteinuria and pathological classification less than IV in children.
      MATERIAL AND METHODS The clinical effects of MMF and low-dose steroid therapy
      were studied in children with Henoch-Schonlein purpura nephritis manifested with
      nephrotic-range proteinuria, normal kidney function, and <50% crescents or
      sclerosing lesions on renal biopsy. We enrolled 32 boys and 29 girls with
      nephrotic-range proteinuria, normal kidney function, and pathological
      classification less than IV on renal biopsy. We treated 41 cases (67.2%) with
      mycophenolate mofetil and low-dose prednisone combined therapy and 20 cases
      (32.8%) were treated with full-dose prednisone alone. RESULTS Short-term response
      was significantly different between 2 groups (chi2=4.371, P=0.037), while no
      significant difference was found in long-term prognosis (chi2=0.419, P=0.522)
      after follow-up. The ROC curve showed that the most appropriate cutoff value was
      30.67 MUg.h/ml for MPA-AUC and the area under the ROC curve was 0.731, with 85.2%
      sensitivity and 64.3% specificity. CONCLUSIONS Mycophenolate mofetil and low-dose
      prednisone combined therapy is a reasonable treatment choice which can promote
      the remission of proteinuria without increasing obvious adverse reactions in
      pediatric HSPN with nephrotic state and pathological classification less than
      grade IV. MPA-AUC more than 30 MUg.h/ml was an appropriate value for MMF in the
      combined therapy with MMF and steroid for treating children with HSPN.

PMID- 28515418
TI  - Automatic Segmentation of Kidneys using Deep Learning for Total Kidney Volume
      Quantification in Autosomal Dominant Polycystic Kidney Disease.
AB  - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited
      disorder of the kidneys. It is characterized by enlargement of the kidneys caused
      by progressive development of renal cysts, and thus assessment of total kidney
      volume (TKV) is crucial for studying disease progression in ADPKD. However,
      automatic segmentation of polycystic kidneys is a challenging task due to severe
      alteration in the morphology caused by non-uniform cyst formation and presence of
      adjacent liver cysts. In this study, an automated segmentation method based on
      deep learning has been proposed for TKV computation on computed tomography (CT)
      dataset of ADPKD patients exhibiting mild to moderate or severe renal
      insufficiency. The proposed method has been trained (n = 165) and tested (n = 79)
      on a wide range of TKV (321.2-14,670.7 mL) achieving an overall mean Dice
      Similarity Coefficient of 0.86 +/- 0.07 (mean +/- SD) between automated and
      manual segmentations from clinical experts and a mean correlation coefficient
      (rho) of 0.98 (p < 0.001) for segmented kidney volume measurements in the entire
      test set. Our method facilitates fast and reproducible measurements of kidney
      volumes in agreement with manual segmentations from clinical experts.

PMID- 28515419
TI  - New insights into ocean sunfish (Mola mola) abundance and seasonal distribution
      in the northeast Atlantic.
AB  - The ocean sunfish, Mola mola, is the largest teleost fish in the world. Despite
      being found in all oceans of the world, little is known about its abundance and
      factors driving its distribution. In this study we provide the first abundance
      estimates for sunfish in offshore waters in the northeast Atlantic and the first
      record of extensive sunfish presence in these waters year-round. Abundance
      estimates and predictive distributions for sunfish in approximately 300,000 km2
      of the northeast Atlantic were derived from large scale offshore aerial surveys
      in 2015-2016 using distance sampling techniques. Generalized additive models of
      sunfish density were fitted to survey data from 17,360 km of line transect effort
      resulting in minimum abundance estimates of 12,702 (CI: 9,864-16,357) in the
      summer (Density = 0.043 ind/km2) and 8,223 individuals (CI: 6,178-10,946)
      (Density = 0.028 ind/km2) in the winter. Density surface models predicted
      seasonal shifts in distribution and highlighted the importance of the mixed layer
      depth, possibly related to thermoregulation following deep foraging dives. The
      abundance estimate and estimated daily consumption of 2,600 tonnes of jellyfish
      in the northeast Atlantic highlights the need to re-assess the importance of this
      species in the pelagic ecosystem, and its role in top-down control of jellyfish
      blooms.

PMID- 28515420
TI  - Vascular Remodelling Relates to an Elevated Oscillatory Shear Index and Relative
      Residence Time in Spontaneously Hypertensive Rats.
AB  - Haemodynamic disorders are common clinical findings in hypertension and lead to
      adverse cardiovascular events. However, the haemodynamic conditions in
      hypertension models are poorly understood. This study aimed to observe the
      characteristics of haemodynamics in spontaneously hypertensive rats (SHRs) and
      antihypertensive-treated SHRs. Twenty-four adult male SHRs and Wistar-Kyoto rats
      (WKYs) were randomly divided into four groups and treated for 7 days as follows:
      WKY-CON (WKYs + saline), WKY-NIF (WKYs + nifedipine, 50 mg/kg/day), SHR-CON (SHRs
      + saline), and SHR-NIF (SHRs + nifedipine). Aortic computational fluid dynamics
      (CFD) models were simulated to obtain the haemodynamic parameters. We found that
      in the hypertensive (SHR-CON) and blood pressure-controlled (SHR-NIF) groups, the
      oscillatory shear index (OSI) and relative residence time (RRT), which are key
      haemodynamics indices, were markedly elevated. Furthermore, there was a
      correlation between both the elevated OSI and RRT with the vascular wall
      thickening in regions near the inner wall of the aortic arch. Our research
      demonstrates that haemodynamics remains disturbed even if the blood pressure is
      normalized. In addition, vascular remodelling may play an important role in
      maintaining elevated OSI and RRT values.

PMID- 28515421
TI  - Comparative transcriptome analysis of Rimicaris sp. reveals novel molecular
      features associated with survival in deep-sea hydrothermal vent.
AB  - Shrimp of the family Alvinocarididae are the predominant megafauna of deep-sea
      hydrothermal vents. However, genome information on this family is currently
      unavailable. In the present study, by employing Illumina sequencing, we performed
      the first de novo transcriptome analysis of the gills of the shrimp Rimicaris sp.
      from the hydrothermal vent in Desmos, Manus Basin. The analysis was conducted in
      a comparative manner with the shrimp taken directly from the vent (GR samples)
      and the shrimp that had been maintained for ten days under normal laboratory
      condition (mGR samples). Among the 128,938 unigenes identified, a large number of
      differentially expressed genes (DEGs) between the GR and mGR samples were
      detected, including 2365 and 1607 genes significantly upregulated and
      downregulated, respectively, in GR. The DEGs covered diverse functional
      categories. Most of the DEGs associated with immunity were downregulated in GR,
      while most of the DEGs associated with sulfur metabolism and detoxification were
      upregulated in GR. These results provide the first comprehensive transcriptomic
      resource for hydrothermal vent Rimicaris and revealed varied categories of genes
      likely involved in deep-sea survival.

PMID- 28515422
TI  - Up regulation and nuclear translocation of Y-box binding protein 1 (YB-1) is
      linked to poor prognosis in ERG-negative prostate cancer.
AB  - Y-box binding protein 1 (YB-1) is an RNA and DNA binding factor with potential
      prognostic cancer. To evaluate the clinical impact of YB-1, a tissue microarray
      with 11,152 prostate cancers was analysed by immunohistochemistry. Cytoplasmic
      and nuclear staining was separately analysed. Cytoplasmic YB-1 was absent or weak
      in normal epithelium but seen in 86,3% of carcinomas. Cytoplasmic staining was
      weak, moderate, and strong in 29.6%, 43.7% and 13.0% of tumours and was
      accompanied by nuclear YB-1 staining in 32.1% of cases. Particularly nuclear
      staining was strongly linked to poor patient prognosis (p < 0.0001). YB-1 protein
      was more abundant in ERG positive (95.1%) than in ERG negative cancers (80.4%; p
      < 0.0001), but any prognostic impact of YB-1 staining was limited to the ERG
      negative subset. Similarly, significant associations with pT stage and Gleason
      grade (p < 0.0001 each) were driven by the ERG negative subset. The significant
      association of YB-1 protein detection with deletions of PTEN, 5q21 and 6q15 fits
      well in the protein's role as an inhibitor of DNA damage dependent cell cycle
      arrest, a role that is likely to induce genomic instability. In summary, the data
      show, that the prognostic impact of YB-1 expression is limited to ERG negative
      prostate cancers.

PMID- 28515423
TI  - MiR-520b as a novel molecular target for suppressing stemness phenotype of head
      neck cancer by inhibiting CD44.
AB  - Cancer stem cells preferentially acquire the specific characteristics of stress
      tolerance and high mobility, allowing them to progress to a therapy-refractive
      state. To identify a critical molecule to regulate cancer stemness is
      indispensable to erratically cure cancer. In this study, we identified miR-520b
      as a novel molecular target to suppress head-neck cancer (HNC) with stemness
      phenotype. MiR-520b inhibited cellular migration and invasion via the mechanism
      of epithelial-mesenchymal transition. It also sensitized cells to therapeutic
      drug and irradiation. Significantly, miR-520b suppressed spheroid cell formation,
      as well as reduced expressions of multiple stemness regulators (Nestin, Twist,
      Nanog, Oct4). The CD44 molecule was identified as a direct target of miR-520b, as
      shown by the reverse correlative expressions, the response to miR-520 modulation,
      the luciferase reporter assay, and the functional rescue analyses. These cellular
      results were confirmed by a tumor xenograft mice study. Administration of miR
      520b dramatically restrained tumorigenesis and liver colonization. Conversely,
      miR-520b silencing led to an acceleration of tumor growth. Taken together, our
      study demonstrated that miR-520b inhibits the malignancy of HNC through
      regulation of cancer stemness conversion by targeting CD44. MiR-520b may serve as
      an emerging therapeutic target that may be further developed for the intervention
      of refractory HNC.

PMID- 28515424
TI  - A Split Ring Resonator Dielectric Probe for Near-Field Dielectric Imaging.
AB  - A single split-ring resonator (SRR) probe for 2D surface mapping and imaging of
      relative dielectric permittivity for the characterisation of composite materials
      has been developed. The imaging principle, the analysis and the sensitivity of
      the SRR surface dielectric probe data is described. The surface dielectric
      properties of composite materials in the frequency range 1-3 GHz have been
      measured based on the magnetic resonance frequency of the transmission loss of
      the SRR dielectric probe when in contact with the surface. The SRR probe
      performance was analysed analytically and using full-wave simulation, and
      predictions showed close agreement with experiment for composite materials with
      spatially varying dielectric permittivity manufactured by 3D printing. The
      spatial and permittivity resolution of the SRR dielectric probe were controlled
      by the geometrical parameters of the SRR which provided flexibility to tune the
      SRR probe. The best accuracy of the dielectric permittivity measurements was
      within 5%.

PMID- 28515425
TI  - New Insight into the Ground State of FePc: A Diffusion Monte Carlo Study.
AB  - We have applied DMC to evaluate relative stability of the possible electronic
      configurations of an isolated FePc under D 4h symmetry, considering some fixed
      nodes generated from different methods. They predict A 2g ground state
      consistently, supporting preceding DFT studies, with confidence overcoming the
      ambiguity about exchange-correlation (XC) functionals. By comparing DMC with
      several XC, we clarified the importance of the short-range exchange to describe
      the relative stability. We examined why the predicted A 2g is excluded from
      possible ground states in the recent ligand field based model. Simplified
      assumptions made in the superposition model are identified to give unreasonably
      less energy gain for A 2g when compared with the reality. The state is found to
      have possible reasons for the stabilization, reducing the occupations from an
      unstable anti-bonding orbital, avoiding double occupation of a spatially
      localized orbital, and gaining exchange energy by putting a triplet spin pair in
      degenerate orbitals.

PMID- 28515428
TI  - Cell morphology governs directional control in swimming bacteria.
AB  - The ability to rapidly detect and track nutrient gradients is key to the
      ecological success of motile bacteria in aquatic systems. Consequently, bacteria
      have evolved a number of chemotactic strategies that consist of sequences of
      straight runs and reorientations. Theoretically, both phases are affected by
      fluid drag and Brownian motion, which are themselves governed by cell geometry.
      Here, we experimentally explore the effect of cell length on control of swimming
      direction. We subjected Escherichia coli to an antibiotic to obtain motile cells
      of different lengths, and characterized their swimming patterns in a homogeneous
      medium. As cells elongated, angles between runs became smaller, forcing a change
      from a run-and-tumble to a run-and-stop/reverse pattern. Our results show that
      changes in the motility pattern of microorganisms can be induced by simple
      morphological variation, and raise the possibility that changes in swimming
      pattern may be triggered by both morphological plasticity and selection on
      morphology.

PMID- 28515426
TI  - Tolerability of Opioid Analgesia for Chronic Pain: A Network Meta-Analysis.
AB  - Aim of this study was to study the tolerability of opioid analgesia by performing
      a network meta-analysis (NMA) of randomized-controlled trials (RCTs) which
      investigated effectiveness of opioids for the management of chronic pain.
      Research articles reporting outcomes of RCT/s comparing 2 or more opioid
      analgesics for the management of chronic pain were obtained by database search.
      Bayesian NMAs were performed to combine direct comparisons between treatments
      with that of indirect simulated evidence. Study endpoints were: incidence of
      adverse events, incidence of constipation, trial withdrawal rate, and patient
      satisfaction with treatment. Outcomes were also compared with conventional meta
      analyses. Thirty-two studies investigating 10 opioid drugs fulfilled the
      eligibility criteria. Tapentadol treatment was top-ranking owing to lower
      incidence of overall adverse events, constipation, and least trial withdrawal
      rate. Tapentadol was followed by oxycodone-naloxone combination in providing
      better tolerability and less trial withdrawal rate. Patient satisfaction was
      found to be higher with oxycodone-naloxone followed by fentanyl and tapentadol.
      These results were in agreement with those achieved with conventional meta
      analyses. Tapentadol and oxycodone-naloxone are found to exhibit better
      tolerability characteristics in comparison with other opioid drugs for the
      management of chronic pain and are associated with low trial withdrawal rate and
      better patient satisfaction.

PMID- 28515427
TI  - Pediatric vision screening using the plusoptiX A12C photoscreener in Chinese
      preschool children aged 3 to 4 years.
AB  - This study evaluated the performance of plusoptiX A12C in detecting amblyopia
      risk factors (ARFs) in Chinese children aged 3-to-4-year. PlusoptiX examination
      was successfully conducted among 1,766 subjects without cycloplegia to detect
      refractive error, asymmetry and media opacity. Cycloplegic retinoscopy (CR) was
      conducted on 357 children suspected of having vision abnormalities. Statistical
      differences between CR and the device were confirmed using the mean spherical
      value (+1.41 +/- 0.87 D versus +1.14 +/- 0.81 D), cylindrical value (-0.47 +/-
      0.64 versus -0.84 +/- 0.78) and spherical equivalent (SE) value (+1.17 +/- 0.84 D
      versus +0.72 +/- 0.64 D) (all P < 0.0001). In the emmetropia group, the
      differences were statistically significant for the cylinder and SE (all P <
      0.0001) but not the sphere (P = 0.33). In the hyperopia group, the differences
      were statistically significant for the sphere, cylinder and SE (all P < 0.0001).
      For refractive and strabismic ARFs detection, the sensitivity, specificity,
      positive predictive value, and negative predictive value were calculated,
      respectively.

PMID- 28515429
TI  - Endocytic uptake of monomeric amyloid-beta peptides is clathrin- and dynamin
      independent and results in selective accumulation of Abeta(1-42) compared to
      Abeta(1-40).
AB  - Intraneuronal accumulation of amyloid-beta (Abeta) peptides represent an early
      pathological feature in Alzheimer's disease. We have therefore utilized flow
      cytometry and confocal microscopy in combination with endocytosis inhibition to
      explore the internalisation efficiency and uptake mechanisms of Abeta(1-40) and
      Abeta(1-42) monomers in cultured SH-SY5Y cells. We find that both variants are
      constitutively internalised via endocytosis and that their uptake is proportional
      to cellular endocytic rate. Moreover, SH-SY5Y cells internalise consistently
      twice the amount of Abeta(1-42) compared to Abeta(1-40); an imaging-based
      quantification showed that cells treated with 1 uM peptide for 8 h contained
      800,000 peptides of Abeta(1-42) and 400,000 of Abeta(1-40). Both variants co
      localised to >90% with lysosomes or other acidic compartments. Dynasore and
      chlorpromazine endocytosis inhibitors were both found to reduce uptake,
      particularly of Abeta(1-42). Overexpression of the C-terminal of the clathrin
      binding domain of AP180, dynamin2 K44A, or Arf6 Q67L did however not reduce
      uptake of the Abeta variants. By contrast, perturbation of actin polymerisation
      and inhibition of macropinocytosis reduced Abeta(1-40) and Abeta(1-42) uptake
      considerably. This study clarifies mechanisms of Abeta(1-40) and Abeta(1-42)
      uptake, pinpoints differences between the two variants and highlights a common
      and putative role of macropinocytosis in the early accumulation of intraneuronal
      Abeta in AD.

PMID- 28515430
TI  - A microfluidic chip for screening individual cancer cells via eavesdropping on
      autophagy-inducing crosstalk in the stroma niche.
AB  - Autophagy is a cellular homeostatic mechanism where proteins and organelles are
      digested and recycled to provide an alternative source of building blocks and
      energy to cells. The role of autophagy in cancer microenvironment is still poorly
      understood. Here, we present a microfluidic system allowing monitoring of the
      crosstalk between single cells. We used this system to study how tumor cells
      induced autophagy in the stromal niche. Firstly, we could confirm that
      transforming growth factor beta1 (TGFbeta1) secreted from breast tumor cells is a
      paracrine mediator of tumor-stroma interaction leading to the activation of
      autophagy in the stroma component fibroblasts. Through proof of concept
      experiments using TGFbeta1 as a model factor, we could demonstrate real time
      monitoring of autophagy induction in fibroblasts by single tumor cells. Retrieval
      of individual tumor cells from the microfluidic system and their subsequent
      genomic analysis was possible, allowing us to determine the nature of the factor
      mediating tumor-stroma interactions. Therefore, our microfluidic platform might
      be used as a promising tool for quantitative investigation of tumor-stroma
      interactions, especially for and high-throughput screening of paracrine factors
      that are secreted from heterogeneous tumor cell populations.

PMID- 28515431
TI  - Early Onset of Nucleate Boiling on Gas-covered Biphilic Surfaces.
AB  - For phase-change cooling schemes for electronics, quick activation of nucleate
      boiling helps safeguard the electronics components from thermal shocks associated
      with undesired surface superheating at boiling incipience, which is of great
      importance to the long-term system stability and reliability. Previous
      experimental studies show that bubble nucleation can occur surprisingly early on
      mixed-wettability surfaces. In this paper, we report unambiguous evidence that
      such unusual bubble generation at extremely low temperatures-even below the
      boiling point-is induced by a significant presence of incondensable gas retained
      by the hydrophobic surface, which exhibits exceptional stability even surviving
      extensive boiling deaeration. By means of high-speed imaging, it is revealed that
      the consequently gassy boiling leads to unique bubble behaviour that stands in
      sharp contrast with that of pure vapour bubbles. Such findings agree
      qualitatively well with numerical simulations based on a diffuse-interface
      method. Moreover, the simulations further demonstrate strong thermocapillary
      flows accompanying growing bubbles with considerable gas contents, which is
      associated with heat transfer enhancement on the biphilic surface in the low
      superheat region.

PMID- 28515432
TI  - High-salt intake negatively regulates fat deposition in mouse.
AB  - High-salt (HS) intake contributes to hypertension and cardiopathy, but the effect
      of HS on fat deposition is controversial. Feed intake, fat mass, the percentage
      of abdominal fat, heat production, rate of oxygen consumption and the respiratory
      exchange ratio of mice on a HS diet were significantly decreased (P < 0.01 or
      0.05) compared with mice on a normal-salt (NS) diet. An in vitro experiment with
      differentiating pre-adipocytes showed reduced fat deposition in the presence of
      high concentrations of NaCl (>0.05 M). Abdominal fat mRNA profiles and protein
      measurements showed that 5 known genes involved in lipolysis were up-regulated
      significantly and 9 genes related to lipogenesis were down-regulated in HS mice.
      Abundant genes and some proteins (ATP2a1, AGT, and ANGPTL4) related to calcium
      ion metabolism or the renin-angiotensin system (RAS) were differentially
      expressed between HS and NS mice. Of special interest, CREB1 phosphorylation
      (S133 and S142), a key factor involved in calcium signaling and other pathways,
      was up-regulated in HS mice. By IPA analysis, a network mediated by calcium was
      established providing the molecular mechanisms underlying the negative effect of
      HS on fat deposition.

PMID- 28515435
TI  - Genetic diversity of armored scales (Hemiptera: Diaspididae) and soft scales
      (Hemiptera: Coccidae) in Chile.
AB  - Scale insects (Sternorrhyncha: Coccoidea) are one of the most invasive and
      agriculturally damaging insect groups. Their management and the development of
      new control methods are currently jeopardized by the scarcity of identification
      data, in particular in regions where no large survey coupling morphological and
      DNA analyses have been performed. In this study, we sampled 116 populations of
      armored scales (Hemiptera: Diaspididae) and 112 populations of soft scales
      (Hemiptera: Coccidae) in Chile, over a latitudinal gradient ranging from 18
      degrees S to 41 degrees S, on fruit crops, ornamental plants and trees. We
      sequenced the COI and 28S genes in each population. In total, 19 Diaspididae
      species and 11 Coccidae species were identified morphologically. From the 63 COI
      haplotypes and the 54 28S haplotypes uncovered, and using several DNA data
      analysis methods (Automatic Barcode Gap Discovery, K2P distance, NJ trees), up to
      36 genetic clusters were detected. Morphological and DNA data were congruent,
      except for three species (Aspidiotus nerii, Hemiberlesia rapax and Coccus
      hesperidum) in which DNA data revealed highly differentiated lineages. More than
      50% of the haplotypes obtained had no high-scoring matches with any of the
      sequences in the GenBank database. This study provides 63 COI and 54 28S barcode
      sequences for the identification of Coccoidea from Chile.

PMID- 28515433
TI  - The sleep-deprived human brain.
AB  - How does a lack of sleep affect our brains? In contrast to the benefits of sleep,
      frameworks exploring the impact of sleep loss are relatively lacking.
      Importantly, the effects of sleep deprivation (SD) do not simply reflect the
      absence of sleep and the benefits attributed to it; rather, they reflect the
      consequences of several additional factors, including extended wakefulness. With
      a focus on neuroimaging studies, we review the consequences of SD on attention
      and working memory, positive and negative emotion, and hippocampal learning. We
      explore how this evidence informs our mechanistic understanding of the known
      changes in cognition and emotion associated with SD, and the insights it provides
      regarding clinical conditions associated with sleep disruption.

PMID- 28515436
TI  - Nimbolide upregulates RECK by targeting miR-21 and HIF-1alpha in cell lines and
      in a hamster oral carcinogenesis model.
AB  - Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent
      inhibitor of matrix metalloproteinases (MMPs) is a common negative target of
      oncogenic signals and a potential therapeutic target for novel drug development.
      Here, we show that sequential RECKlessness stimulates angiogenesis and Notch
      signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal
      pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and
      chemointervention. We also report the chemotherapeutic effect of nimbolide, a
      limonoid from the neem tree (Azadirachta indica) based on the upregulation of
      RECK as well as modulation of the expression of key molecules involved in
      invasion and angiogenesis. We demonstrate that nimbolide upregulates RECK by
      targeting miR-21, and HIF-1alpha resulting in reduced MMP activity and blockade
      of VEGF and Notch signalling. Nimbolide reduced microvascular density, confirming
      its anti-angiogenic potential. Molecular docking analysis revealed interaction of
      nimbolide with HIF-1alpha. Additionally, we demonstrate that nimbolide
      upregulates RECK expression via downregulation of HIF-1alpha and miR-21 by
      overexpression and knockdown experiments in SCC4 and EAhy926 cell lines. Taken
      together, these findings provide compelling evidence that targeting RECK, a
      keystone protein that regulates mediators of invasion and angiogenesis with
      phytochemicals such as nimbolide may be a robust therapeutic approach to prevent
      oral cancer progression.

PMID- 28515437
TI  - CoCO3 from one-step micro-emulsion method as electrode materials for Faradaic
      capacitors.
AB  - Faradaic capacitor (FC) has been widely investigated during the past few decades,
      and dozens of prototypes have been proposed. However, it has not reached its full
      potential. In this work, we demonstrate a kind of FC comprising of a CoCO3
      electrode. Synthesized through a micro-emulsion route, such CoCO3 shows low
      crystallinity and porous wool-ball structures stacked by needle-like individuals.
      It shows desirable electrochemical properties in terms of excellent high-rate
      performance and high reversibility. Also, it could deliver a capacitance of 440
      F.g-1 at 1 A.g-1, and shows no capacitance decay after 1000 cycles. Since metal
      carbonate is capable of delivering good electrochemical performances and its
      preparation is easier and more cost-efficient, it should be a feasible candidate
      for electrode material of FC.

PMID- 28515434
TI  - Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer
      disease.
AB  - Cerebral blood flow (CBF) regulation is essential for normal brain function. The
      mammalian brain has evolved a unique mechanism for CBF control known as
      neurovascular coupling. This mechanism ensures a rapid increase in the rate of
      CBF and oxygen delivery to activated brain structures. The neurovascular unit is
      composed of astrocytes, mural vascular smooth muscle cells and pericytes, and
      endothelia, and regulates neurovascular coupling. This Review article examines
      the cellular and molecular mechanisms within the neurovascular unit that
      contribute to CBF control, and neurovascular dysfunction in neurodegenerative
      disorders such as Alzheimer disease.

PMID- 28515438
TI  - Mitochondrial retrograde signaling connects respiratory capacity to thermogenic
      gene expression.
AB  - Mitochondrial respiration plays a crucial role in determining the metabolic state
      of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well
      as through additional mechanisms. Here, we show that respiration-dependent
      retrograde signaling from mitochondria to nucleus contributes to genetic and
      metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a
      potent regulator of mitochondrial transcription and respiratory capacity,
      triggers down-regulation of thermogenic genes, promoting a storage phenotype in
      BAT. This retrograde regulation functions by inhibiting the recruitment of
      PPARgamma to the regulatory elements of thermogenic genes. Reducing cytosolic
      Ca2+ reverses the attenuation of thermogenic genes in brown adipocytes with
      impaired respiratory capacity, while induction of cytosolic Ca2+ is sufficient to
      attenuate thermogenic gene expression, indicating that cytosolic Ca2+ mediates
      mitochondria-nucleus crosstalk. Our findings suggest respiratory capacity governs
      thermogenic gene expression and BAT function via mitochondria-nucleus
      communication, which in turn leads to either a thermogenic or storage mode.

PMID- 28515439
TI  - The Biomechanics Behind Extreme Osteophagy in Tyrannosaurus rex.
AB  - Most carnivorous mammals can pulverize skeletal elements by generating tooth
      pressures between occluding teeth that exceed cortical bone shear strength,
      thereby permitting access to marrow and phosphatic salts. Conversely, carnivorous
      reptiles have non-occluding dentitions that engender negligible bone damage
      during feeding. As a result, most reptilian predators can only consume bones in
      their entirety. Nevertheless, North American tyrannosaurids, including the giant
      (13 metres [m]) theropod dinosaur Tyrannosaurus rex stand out for habitually
      biting deeply into bones, pulverizing and digesting them. How this mammal-like
      capacity was possible, absent dental occlusion, is unknown. Here we analyzed T.
      rex feeding behaviour from trace evidence, estimated bite forces and tooth
      pressures, and studied tooth-bone contacts to provide the answer. We show that
      bone pulverization was made possible through a combination of: (1) prodigious
      bite forces (8,526-34,522 newtons [N]) and tooth pressures (718-2,974 megapascals
      [MPa]) promoting crack propagation in bones, (2) tooth form and dental arcade
      configurations that concentrated shear stresses, and (3) repetitive, localized
      biting. Collectively, these capacities and behaviors allowed T. rex to finely
      fragment bones and more fully exploit large dinosaur carcasses for sustenance
      relative to competing carnivores.

PMID- 28515441
TI  - Fluorescence dynamics of the biosynthesized CdSe quantum dots in Candida utilis.
AB  - Organisms served as factories of bio-assembly of nanoparticles attracted a lot of
      attentions due to the safe, economic and environmental-benignity traits,
      especially the fabrication of the super fluorescence properties quantum dots
      (QDs). However, information about the developmental dynamics of QDs in living
      organisms is still lacking. In this work, we synthesized cadmium-selenium (CdSe)
      QDs in Candida utilis WSH02-08, and then tracked and quantitatively characterized
      the developmental dynamics (photoactivation, photostable and photobleaching
      processes) of bio-QDs by translating fluorescence microscopy movies into visual
      quantitative curve. These findings shed light on the fluorescence properties of
      the bio-assembled QDs and are expected to accelerate the applications of the
      synthesized QDs in vivo. It provided a new way to screen bio-QDs and monitor the
      quality of QDs in vivo.

PMID- 28515442
TI  - Interplay between Alternative Splicing and Alternative Polyadenylation Defines
      the Expression Outcome of the Plant Unique OXIDATIVE TOLERANT-6 Gene.
AB  - Pre-mRNA alternative splicing and alternative polyadenylation have been
      implicated to play important roles during eukaryotic gene expression. However,
      much remains unknown regarding the regulatory mechanisms and the interactions of
      these two processes in plants. Here we focus on an Arabidopsis gene OXT6
      (Oxidative Tolerant-6) that has been demonstrated to encode two proteins through
      alternative splicing and alternative polyadenylation. Specifically, alternative
      polyadenylation at Intron-2 of OXT6 produces a transcript coding for AtCPSF30, an
      Arabidopsis ortholog of 30 kDa subunit of the Cleavage and Polyadenylation
      Specificity Factor. On the other hand, alternative splicing of Intron-2 generates
      a longer transcript encoding a protein named AtC30Y, a polypeptide including most
      part of AtCPSF30 and a YT521B domain. To investigate the expression outcome of
      OXT6 in plants, a set of mutations were constructed to alter the splicing and
      polyadenylation patterns of OXT6. Analysis of transgenic plants bearing these
      mutations by quantitative RT-PCR revealed a competition relationship between
      these two processes. Moreover, when both splice sites and poly(A) signals were
      mutated, polyadenylation became the preferred mode of OXT6 processing. These
      results demonstrate the interplay between alternative splicing and alternative
      polyadenylation, and it is their concerted actions that define a gene's
      expression outcome.

PMID- 28515440
TI  - A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm
      Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis.
AB  - Unlike individual, free-floating planktonic bacteria, biofilms are surface
      attached communities of slow- or non-replicating bacteria encased within a
      protective extracellular polymeric matrix enabling persistent bacterial
      populations to tolerate high concentrations of antimicrobials. Our current
      antibacterial arsenal is composed of growth-inhibiting agents that target rapidly
      dividing planktonic bacteria but not metabolically dormant biofilm cells. We
      report the first modular synthesis of a library of 20 halogenated phenazines
      (HP), utilizing the Wohl-Aue reaction, that targets both planktonic and biofilm
      cells. New HPs, including 6-substituted analogues, demonstrate potent
      antibacterial activities against MRSA, MRSE and VRE (MIC = 0.003-0.78 uM). HPs
      bind metal(II) cations and demonstrate interesting activity profiles when co
      treated in a panel of metal(II) cations in MIC assays. HP 1 inhibited RNA and
      protein biosynthesis while not inhibiting DNA biosynthesis using 3H-radiolabeled
      precursors in macromolecular synthesis inhibition assays against MRSA. New HPs
      reported here demonstrate potent eradication activities (MBEC = 0.59-9.38 uM)
      against MRSA, MRSE and VRE biofilms while showing minimal red blood cell lysis or
      cytotoxicity against HeLa cells. PEG-carbonate HPs 24 and 25 were found to have
      potent antibacterial activities with significantly improved water solubility. HP
      small molecules could have a dramatic impact on persistent, biofilm-associated
      bacterial infection treatments.

PMID- 28515443
TI  - Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R
      PI3K-Akt-Tor Action.
AB  - Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K
      AKT-TOR signaling pathway is linked to major human diseases, and key components
      of this pathway are targets for therapeutic intervention. Current assays are
      molecular target- or cell culture-based platforms. Due to the great in vivo
      complexities inherited in this pathway, there is an unmet need for whole organism
      based assays. Here we report the development of a zebrafish transgenic line,
      Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt
      Tor signaling in epithelial cells in real-time. This platform is well suited for
      high-throughput assays and real-time cell cycle analysis. Using this platform,
      the dynamics of epithelial cell proliferation in response to low [Ca2+] stress
      and the distinct roles of Torc1 and Torc2 were elucidated. The availability of
      Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based
      discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling
      pathway.

PMID- 28515444
TI  - Orbital angular momentum analysis for giant spin splitting in solids and
      nanostructures.
AB  - Giant spin splitting (GSS) of electronic bands, which is several orders of
      magnitude greater than the standard Rashba effect has been observed in various
      systems including noble-metal surfaces and thin films of transition-metal
      dichalcogenides. Previous studies reported that orbital angular momentum (OAM) is
      not quenched in some GSS materials and that the atomic spin-orbit interaction
      (SOI) generates spin splitting in some solid states via the interorbital hopping.
      Although the unquenched OAM may be closely related to the interorbital hopping,
      their relationship is hardly studied in the aspect of using the unquenched OAM as
      a control parameter of GSS. Here, we analyze OAM in GSS materials by using the
      interorbital-hopping mechanism and first-principles calculations. We report that
      the interatomic hopping between different-parity orbitals, which is generated by
      specific broken mirror symmetry, produces k-dependent OAM, resulting in valley
      dependent GSS in WSe2 monolayer, Rashba-type GSS in Au (111) surface, and
      Dresselhaus-type GSS in bulk HgTe. We also demonstrate systematic control of OAM
      by pressure, external fields, and substrates, thereby controlling the spin
      splitting, and discuss the temperature dependence of OAM. Our results provide a
      simplified picture for systematic design and control of GSS materials.

PMID- 28515445
TI  - Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of
      triple-negative breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking
      targeted therapy currently. Recent studies imply that protein kinase C may play
      important roles in TNBC development and could be a specific target. In this
      study, we evaluated the anti-proliferative activity of PKC inhibitor
      chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively
      inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as
      demonstrated by in vitro cell proliferation assay and colony formation assay, as
      well as evidenced by in vivo xenograft assay. The selective anti-proliferative
      effect of chelerythrine was associated with induction of apoptosis in TNBC cell
      lines. We further demonstrated that PKN2, one of the PKC subtypes, was highly
      expressed in TNBC cell lines, and knocking down PKN2 in TNBC cells inhibited
      colony formation and xenograft growth. This indicates that PKN2 is required for
      the survival of TNBC cells, and could be the target mediates the selective
      activity of chelerythrine. Finally, combination of chelerythrine and chemotherapy
      reagent taxol showed synergistic/additive effect on TNBC cell lines. Our results
      suggest chelerythrine or other PKC inhibitors may be promising regimens for TNBC
      tumors.

PMID- 28515446
TI  - Phase-channel dynamics reveal the role of impurities and screening in a quasi-one
      dimensional charge-density wave system.
AB  - Charge density waves (CDWs), i.e. the periodic spatial modulation of coupled
      electronic and lattice density, are ubiquitous in low-dimensional conductors and
      have taken on renewed relevance due their role in state-of-the-art materials,
      e.g. high-T c superconductors, topological insulators and low-dimensional carbon.
      As CDWs are described by a complex order parameter to represent both the
      amplitude and phase, they are formally analogous to BCS superconductors and spin
      waves, providing a prototype of collective phenomena for the further development
      of field theories and ab-initio calculations of complex solids. The low-energy
      excitations are mixed electron-phonon quanta which ideally separate into an
      amplitude and phase channel, and provide a sensitive probe of the ground state
      and non-equilibrium dynamics, including ultrafast photoinduced phase transitions.
      While recent studies of the amplitude modes have brought substantial progress
      aided by a phenomenological Ginzburg-Landau framework, we focus here on the phase
      modes using ultrafast terahertz spectroscopy. Experiments on K0.3MoO3 provide a
      more complete picture, and reveal a high sensitivity to interactions with
      impurities and screening effects from photogenerated carriers, both of which can
      be accounted for by generalizations of the model. Moreover, our considerations
      emphasize the need to revisit the treatment of inherent electronic damping in
      quantum-mechanical CDW theories.

PMID- 28515447
TI  - DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in
      a homeodomain-dependent manner in human trophoblast-derived cells.
AB  - The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1
      (GCM1) have been shown to coordinate the specific regulation of PGF in human
      trophoblast cell lines. While both factors independently have a positive effect
      on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite
      this understanding, potential mechanisms accounting for this regulatory
      interaction remain unexplored. We identify physical and functional interactions
      between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by
      performing immunoprecipitation and mammalian one hybrid assays. Studies revealed
      that DLX3 binding reduced the transcriptional activity of GCM1, providing a
      mechanistic explanation of their functional antagonism in regulating PGF promoter
      activity. The DLX3 homeodomain (HD) was essential for DLX3-GCM1 interaction, and
      that the HD together with the DLX3 amino- or carboxyl-terminal domains was
      required for maximal inhibition of GCM1. Interestingly, a naturally occurring
      DLX3 mutant that disrupts the carboxyl-terminal domain leading to tricho-dento
      osseous syndrome in humans displayed activities indistinguishable from wild type
      DLX3 in this system. Collectively, our studies demonstrate that DLX3 physically
      interacts with GCM1 and inhibits its transactivation activity, suggesting that
      DLX3 and GCM1 may form a complex to functionally regulate placental cell function
      through modulation of target gene expression.

PMID- 28515448
TI  - Involvement Of Vascular Aldosterone Synthase In Phosphate-Induced Osteogenic
      Transformation Of Vascular Smooth Muscle Cells.
AB  - Vascular calcification resulting from hyperphosphatemia is a major determinant of
      mortality in chronic kidney disease (CKD). Vascular calcification is driven by
      aldosterone-sensitive osteogenic transformation of vascular smooth muscle cells
      (VSMCs). We show that even in absence of exogenous aldosterone, silencing and
      pharmacological inhibition (spironolactone, eplerenone) of the mineralocorticoid
      receptor (MR) ameliorated phosphate-induced osteo-/chondrogenic transformation of
      primary human aortic smooth muscle cells (HAoSMCs). High phosphate concentrations
      up-regulated aldosterone synthase (CYP11B2) expression in HAoSMCs. Silencing and
      deficiency of CYP11B2 in VSMCs ameliorated phosphate-induced osteogenic
      reprogramming and calcification. Phosphate treatment was followed by nuclear
      export of APEX1, a CYP11B2 transcriptional repressor. APEX1 silencing up
      regulated CYP11B2 expression and stimulated osteo-/chondrogenic transformation.
      APEX1 overexpression blunted the phosphate-induced osteo-/chondrogenic
      transformation and calcification of HAoSMCs. Cyp11b2 expression was higher in
      aortic tissue of hyperphosphatemic klotho-hypomorphic (kl/kl) mice than in wild
      type mice. In adrenalectomized kl/kl mice, spironolactone treatment still
      significantly ameliorated aortic osteoinductive reprogramming. Our findings
      suggest that VSMCs express aldosterone synthase, which is up-regulated by
      phosphate-induced disruption of APEX1-dependent gene suppression. Vascular
      CYP11B2 may contribute to stimulation of VSMCs osteo-/chondrogenic transformation
      during hyperphosphatemia.

PMID- 28515449
TI  - The role of stride frequency for walk-to-run transition in humans.
AB  - It remains unclear why humans spontaneously shift from walking to running at a
      certain point during locomotion at gradually increasing velocity. We show that a
      calculated walk-to-run transition stride frequency (70.6 +/- 3.2 strides min-1)
      agrees with a transition stride frequency (70.8 +/- 3.1 strides min-1) predicted
      from the two stride frequencies applied during treadmill walking and running at
      freely chosen velocities and freely chosen stride frequencies. The agreement is
      based on Bland and Altman's statistics. We found no essential mean relative
      difference between the two transition frequencies, i.e. -0.5% +/- 4.2%, as well
      as limits of agreement of -8.7% and 7.7%. The particular two freely chosen stride
      frequencies used for prediction are considered behavioural attractors. Gait is
      predicted to be shifted from walking to running when the stride frequency starts
      getting closer to the running attractor than to the walking attractor. In
      particular, previous research has focussed on transition velocity and
      optimisation theories based on minimisation of, e.g., energy turnover or
      biomechanical loadings of the legs. Conversely, our data support that the central
      phenomenon of walk-to-run transition during human locomotion could be influenced
      by behavioural attractors in the form of stride frequencies spontaneously
      occurring during behaviourally unrestricted gait conditions of walking and
      running.

PMID- 28515450
TI  - Microfluidic Sorting of Cells by Viability Based on Differences in Cell
      Stiffness.
AB  - The enrichment of viable cells is an essential step to obtain effective products
      for cell therapy. While procedures exist to characterize the viability of cells,
      most methods to exclude nonviable cells require the use of density gradient
      centrifugation or antibody-based cell sorting with molecular labels of cell
      viability. We report a label-free microfluidic technique to separate live and
      dead cells that exploits differences in cellular stiffness. The device uses a
      channel with repeated ridges that are diagonal with respect to the direction of
      cell flow. Stiff nonviable cells directed through the channel are compressed and
      translated orthogonally to the channel length, while soft live cells follow
      hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high
      purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a
      sorting parameter as nonviable cells were substantially stiffer than live cells.
      To highlight the utility for hematopoietic stem cell transplantation, frozen
      samples of cord blood were thawed and the purity of viable nucleated cells was
      increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus,
      the microfluidic stiffness sorting can simply and efficiently obtain highly pure
      populations of viable cells.

PMID- 28515451
TI  - HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral
      chordomas.
AB  - Chordomas are rare tumours of the bone arising along the spine from clivus to
      sacrum. We compared three chordoma cell lines of the clivus region including the
      newly established clivus chordoma cell line, U-CH14, with nine chordoma cell
      lines originating from sacral primaries by morphology, on genomic and expression
      levels and with patient samples from our chordoma tissue bank. Clinically,
      chordomas of the clivus were generally smaller in size at presentation and
      patients with sacral chordomas had more metastases and more often recurrent
      disease. All chordoma cell lines had a typical physaliphorous morphology and
      expressed brachyury, S100-protein and cytokeratin. By expression analyses we
      detected differentially expressed genes in the clivus derived cell lines as
      compared to the sacral cell lines. Among these were HOXA7, HOXA9, and HOXA10
      known to be important for the development of the anterior-posterior body axis.
      These results were confirmed by qPCR. Immunohistologically, clivus chordomas had
      no or very low levels of HOXA10 protein while sacral chordomas showed a strong
      nuclear positivity in all samples analysed. This differential expression of HOX
      genes in chordomas of the clivus and sacrum suggests an oncofetal mechanism in
      gene regulation linked to the anatomic site.

PMID- 28515452
TI  - Trends and Outcomes of Surgical Treatment for Colorectal Cancer between 2004 and
      2012- an Analysis using National Inpatient Database.
AB  - Limited data are available for the epidemiology and outcome of colorectal cancer
      in relation to the three main surgical treatment modalities (open, laparoscopic
      and robotic). Using the US National Inpatient Sample database from 2004 to 2012,
      we identified 1,265,684 hospitalized colorectal cancer patients. Over the 9 year
      period, there was a 13.5% decrease in the number of hospital admissions and a
      43.5% decrease in in-hospital mortality. Comparing the trend of surgical
      modalities, there was a 35.4% decrease in open surgeries, a 3.5 fold increase in
      laparoscopic surgeries, and a 41.3 fold increase in robotic surgeries.
      Nonetheless, in 2012, open surgery still remained the preferred surgical
      treatment modality (65.4%), followed by laparoscopic (31.2%) and robotic
      surgeries (3.4%). Laparoscopic and robotic surgeries were associated with lower
      in-hospital mortality, fewer complications, and shorter length of stays, which
      might be explained by the elective nature of surgery and earlier tumor grades.
      After excluding patients with advanced tumor grades, laparoscopic surgery was
      still associated with better outcomes and lower costs than open surgery. On the
      contrary, robotic surgery was associated with the highest costs, without
      substantial outcome benefits over laparoscopic surgery. More studies are required
      to clarify the cost-effectiveness of robotic surgery.

PMID- 28515453
TI  - Validation of reference genes for the normalization of the RT-qPCR gene
      expression of virulence genes of Erwinia amylovora in apple shoots.
AB  - To study the expression of pathogenicity-related genes in Erwinia amylovora,
      seven candidate reference genes (ffh, glyA, gyrA, proC, pykA, recA, rpoB) were
      selected and validated with the following five different mathematic algorithms:
      geNorm, NormFinder, BestKeeper, the delta CT method and the RefFinder web-based
      tool. An overall comprehensive ranking output from each of the selected software
      programs revealed that proC and recA, followed by ffh and pykA, were the most
      stably expressed genes and can be recommended for the normalization of RT-qPCR
      data. A combination of the three reference genes, proC, recA and ffh, allowed for
      the accurate expression analysis of amsB and hrpN genes and the calculation of
      their fold change in E. amylovora after its infection of susceptible and
      resistant apple cultivars. To the best of our knowledge, this is the first study
      presenting a list of the most suitable reference genes for use in the relative
      quantification of target gene expression in E. amylovora in planta, selected on
      the basis of a multi-algorithm analysis.

PMID- 28515454
TI  - A quantitative shRNA screen identifies ATP1A1 as a gene that regulates
      cytotoxicity by aurilide B.
AB  - Genome-wide RNA interference (RNAi) with pooled and barcoded short-hairpin RNA
      (shRNA) libraries provides a powerful tool for identifying cellular components
      that are relevant to the modes/mechanisms of action (MoA) of bioactive compounds.
      shRNAs that affect cellular sensitivity to a given compound can be identified by
      deep sequencing of shRNA-specific barcodes. We used multiplex barcode sequencing
      technology by adding sample-specific index tags to PCR primers during sequence
      library preparation, enabling parallel analysis of multiple samples. An shRNA
      library screen with this system revealed that downregulation of ATP1A1, an alpha
      subunit of Na+/K+ ATPase, conferred significant sensitivity to aurilide B, a
      natural marine product that induces mitochondria-mediated apoptosis. Combined
      treatment with ouabain which inhibits Na+/K+ ATPase by targeting alpha-subunits
      potentiated sensitivity to aurilide B, suggesting that ATP1A1 regulates
      mitochondria-mediated apoptosis. Our results indicate that multiplex sequencing
      facilitates the use of pooled shRNA library screening for the identification of
      combination drug therapy targets.

PMID- 28515455
TI  - Comparative genomic analysis reveals the environmental impacts on two
      Arcticibacter strains including sixteen Sphingobacteriaceae species.
AB  - How the genomic diversity of species is driven by geographical isolation and
      environmental factors are not well understood for cold environments. Here, the
      environmental stress responses of two phylogenetically close Arcticibacter
      strains, A. eurypsychrophilus MJ9-5 and A. svalbardensis MN12-7, isolated from a
      Tibetan Plateau glacier and Svalbard soil, were analyzed. The comparative genomic
      analysis was performed with sixteen other related Sphingobacteriaceae species.
      Analyses of the relationships between growth temperature and genome composition,
      cold and heat shock genes showed that genomic adaption characteristics were more
      obvious when the strains were grouped by their upper limit in growth temperature,
      rather than by their minimal or optimal growth temperatures for
      Sphingobacteriaceae species. The very divergent genetic distance of genome
      fractions assigned to the functions of 'secondary metabolism', 'dormancy and
      sporulation' and 'metabolism of aromatic compounds' indicated the heterogeneous
      evolution of genes under different environmental pressures of the
      Sphingobacteriaceae species. The greatest differences between strains MJ9-5 and
      MN12-7 occurred in the genes devoted to the CRISPRs, osmotic adaption and
      metabolism of monosaccharides, nitrogen and aromatic compounds. These
      distinctions corresponded to two different environmental pressures, salinity and
      nutritional level, in the glacier ice and Svalbard soil environments.

PMID- 28515456
TI  - Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats
      after short-term feeding with high fat diet.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and
      is often associated with lipotoxic injury, defective mitochondrial function, and
      insulin resistance. Thyroid hormones (THs) are important regulators of hepatic
      lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3)
      have shown promising results in lowering hepatic fat content in various models of
      NAFLD. In this study, we used a targeted metabolomics approach to investigate the
      differential effects of T2 and T3 on the early metabolic adaptation in the livers
      of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our
      results showed that both T2 and T3 strongly induced autophagy and intra-hepatic
      acylcarnitine flux but prevented the generation of sphingolipid/ceramides in
      animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat
      content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways
      caused by HFD. In summary, we have identified and characterized the effects of T2
      and T3 on hepatic metabolism during short-term exposure to HFD. These findings
      illuminate the common and divergent metabolic pathways by T2 and T3 that also may
      be important in the prevention and treatment of NAFLD.

PMID- 28515457
TI  - Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from
      that of YAP-TEAD complex.
AB  - The Hippo pathway is a tumor suppressor pathway that is implicated in the
      regulation of organ size. The pathway has three components: the upstream
      regulatory factors, the kinase core, and the downstream transcriptional
      machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD
      (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the
      transcription of growth-promoting genes. Herein, we report the crystal structure
      of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to
      the published YAP-TEAD structure. The second is a unique binding mode, whereby
      two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the
      latter using cross-linking and multi-angle light scattering. Using siRNA, we
      showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly,
      results from luciferase assays, using YAP/TAZ transfected or knockdown cells,
      give support to the non-redundancy of YAP/TAZ co-activators in regulating gene
      expression in the Hippo pathway.

PMID- 28515458
TI  - Floccular fossa size is not a reliable proxy of ecology and behaviour in
      vertebrates.
AB  - The cerebellar floccular and parafloccular lobes are housed in fossae of the
      periotic region of the skull of different vertebrates. Experimental evidence
      indicates that the lobes integrate visual and vestibular information and control
      the vestibulo-ocular reflex, vestibulo-collic reflex, smooth pursuit and gaze
      holding. Multiple paleoneuroanatomy studies have deduced the behaviour of fossil
      vertebrates by measuring the floccular fossae (FF). These studies assumed that
      there are correlations between FF volume and behaviour. However, these
      assumptions have not been fully tested. Here, we used micro-CT scans of extant
      mammals (47 species) and birds (59 species) to test six possible morphological
      functional associations between FF volume and ecological/behavioural traits of
      extant animals. Behaviour and ecology do not explain FF volume variability in
      four out of six variables tested. Two variables with significant results require
      further empirical testing. Cerebellum plasticity may explain the lack of
      statistical evidence for the hypotheses tested. Therefore, variation in FF volume
      seems to be better explained by a combination of factors such as anatomical and
      phylogenetic evolutionary constraints, and further empirical testing is required.

PMID- 28515459
TI  - Associations between Left Ventricular Cavity Size and Cardiac Function and
      Overload Determined by Natriuretic Peptide Levels and a Covariance Structure
      Analysis.
AB  - The effects of left ventricular (LV) cavity size on cardiac function and overload
      have not yet been fully elucidated. We performed a covariance structure analysis
      and drew theoretical path models to clarify the effects of hemodynamic parameters
      on the stroke volume index (SVI) as a marker of cardiac function and on the
      plasma B-type natriuretic peptide (BNP) level as a marker of cardiac overload. We
      simultaneously measured various hemodynamic parameters and the BNP levels during
      cardiac catheterization in 1,715 inpatients of our institution. The current path
      models tested the validity of the Frank-Starling law in patients with heart
      failure using the SVI, the LV end-systolic volume index (LVESVI) and the LV end
      diastolic volume index (LVEDVI). Using the BNP levels, the path models clearly
      demonstrated that LVESVI substantially augmented cardiac overload, whereas LVEDVI
      palliated this parameter. These volume indices exerted opposite effects on
      cardiac function and overload. These results advance the understanding of the
      relationships between LV cavity size and both cardiac function and overload and
      indicate the increasing importance of LV diastolic volume in heart failure and
      the utility of LVESVI as an important marker of cardiac remodeling for further
      relevant studies.

PMID- 28515461
TI  - Variation of Nanostructures, Molecular Interactions, and Anisotropic Elastic
      Moduli of Lignocellulosic Cell Walls with Moisture.
AB  - A combination of experimental, theoretical and numerical studies is used to
      investigate the variation of elastic moduli of lignocellulosic (bamboo) fiber
      cell walls with moisture content (MC). Our Nanoindentation results show that the
      longitudinal elastic modulus initially increased to a maximum value at about 3%
      MC and then decreased linearly with increasing MC. In contrast, the transverse
      moduli decrease linearly with MC. We showed that amorphous materials in cell
      walls have key roles in the variation of elastic modulus with increasing MC.
      Elastic modulus of lignin, calculated by molecular dynamics simulations,
      increases initially with increasing MC, and then decreases. In contrast, elastic
      modulus of hemicellulose decreases constantly with MC. Below 10% MC, water
      molecules tend to break hydrogen bonds between polymer chains and form new
      hydrogen bond bridges between the polymer chains, while above 10% MC, water
      molecules aggregate together and create nano-droplets inside the materials.
      During the process of bridging, the fractional free volume of lignin decreases.
      The free volume reduction along with formation of hydrogen bond bridges causes a
      growth in elastic modulus of lignin at low MC. The constant increase of
      hemicellulose free volume, however, causes the aggregation of voids in the system
      and diminution of elastic properties.

PMID- 28515462
TI  - Autoimmunity: HLA-mediated protection in Goodpasture disease.

PMID- 28515460
TI  - Chlamydia trachomatis infection of human endometrial stromal cells induces
      defective decidualisation and chemokine release.
AB  - Miscarriage affects ~20% of pregnancies and maternal infections account for ~15%
      of early miscarriages. Chlamydia trachomatis (Ct) has been associated with
      miscarriage but the underlying mechanisms are unknown. Successful implantation
      requires endometrial stromal cell (ESC) decidualisation. Maintenance of pregnancy
      requires angiogenesis, establishment of the correct cellular milieu and
      trophoblast invasion, all of which involve the action of chemokines. Our
      objective was to determine whether Ct infection impacts upon ESC decidualisation
      and chemokine secretion. Human primary ESC were decidualised in-vitro, infected
      with Ct serovar E, and changes in expression of genes of interest were measured
      using RT-PCR, proteomic array and ELISA. We demonstrate for the first time that
      Ct can infect and proliferate in ESC. Expression of the decidualisation marker
      prolactin was decreased in Ct-infected ESC at both mRNA and protein levels. Ct
      infection altered the chemokine profile of decidualised ESC as shown by proteomic
      array. Chemokines CXCL12 and CXCL16, important for trophoblast invasion, were
      analysed further and expression was reduced in infected decidualised cells at
      mRNA and protein levels. Our data indicate that Ct infection of ESC impairs
      decidualisation and alters chemokine release. These findings at least partially
      explain how Ct infection could result in adverse pregnancy outcomes.

PMID- 28515463
TI  - Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases.
AB  - Owing to the key role of trehalose in pathogenic organisms, there has recently
      been growing interest in trehalose metabolism for therapeutic purposes. Trehalose
      6-phosphate phosphatase (TPP) is a pivotal enzyme in the most prominent
      biosynthesis pathway (OtsAB). Here, we compare the enzyme characteristics of
      recombinant TPPs from five important nematode and bacterial pathogens, including
      three novel members of this protein family. Analysis of the kinetics of trehalose
      6-phosphate hydrolysis reveals that all five enzymes display a burst-like kinetic
      behaviour which is characterised by a decrease of the enzymatic rate after the
      pre-steady state. The observed super-stoichiometric burst amplitudes can be
      explained by multiple global conformational changes in members of this enzyme
      family during substrate processing. In the search for specific TPP inhibitors,
      the trapping of the complex conformational transitions in TPPs during the
      catalytic cycle may present a worthwhile strategy to explore.

PMID- 28515466
TI  - Disentangling the intricate atomic short-range order and electronic properties in
      amorphous transition metal oxides.
AB  - Solid state materials with crystalline order have been well-known and
      characterized for almost a century while the description of disordered materials
      still bears significant challenges. Among these are the atomic short-range order
      and electronic properties of amorphous transition metal oxides [aTMOs], that have
      emerged as novel multifunctional materials due to their optical switching
      properties and high-capacity to intercalate alkali metal ions at low voltages.
      For decades, research on aTMOs has dealt with technological optimization.
      However, it remains challenging to unveil their intricate atomic short-range
      order. Currently, no systematic and broadly applicable methods exist to assess
      atomic-size structure, and since electronic localization is structure-dependent,
      still there are not well-established optical and electronic mechanisms for
      modelling the properties of aTMOs. We present state-of-the-art systematic
      procedures involving theory and experiment in a self-consistent computational
      framework to unveil the atomic short-range order and its role for the electronic
      properties. The scheme is applied to amorphous tungsten trioxide aWO3, which is
      the most studied electrochromic aTMO in spite of its unidentified atomic-size
      structure. Our approach provides a one-to-one matching of experimental data and
      corresponding model structure from which electronic properties can be directly
      calculated in agreement with the electronic transitions observed in the XANES
      spectra.

PMID- 28515464
TI  - Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of
      Disease Complications.
AB  - Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse
      outcomes but the pathological interactions between DM and TB remain incompletely
      understood. We performed an integrative analysis of whole blood gene expression
      and plasma analytes, comparing South Indian TB patients with and without DM to
      diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines
      and growth factors delineated a distinct biosignature in comorbid TBDM in this
      cohort. Transcriptional profiling revealed elements in common with published TB
      signatures from cohorts that excluded DM. Neutrophil count correlated with the
      molecular degree of perturbation, especially in TBDM patients. Body mass index
      and HDL cholesterol were negatively correlated with molecular degree of
      perturbation. Diabetic complication pathways including several pathways linked to
      epigenetic reprogramming were activated in TBDM above levels observed with DM
      alone. Our data provide a rationale for trials of host-directed therapies in
      TBDM, targeting neutrophilic inflammation and diabetic complication pathways to
      address the greater morbidity and mortality associated with this increasingly
      prevalent dual burden of communicable and non-communicable diseases.

PMID- 28515465
TI  - Gender-specific differential expression of exosomal miRNA in synovial fluid of
      patients with osteoarthritis.
AB  - The pathogenesis of osteoarthritis (OA) is poorly understood, and therapeutic
      approaches are limited to preventing progression of the disease. Recent studies
      have shown that exosomes play a vital role in cell-to-cell communication, and
      pathogenesis of many age-related diseases. Molecular profiling of synovial fluid
      derived exosomal miRNAs may increase our understanding of OA progression and may
      lead to the discovery of novel biomarkers and therapeutic targets. In this
      article we report the first characterization of exosomes miRNAs from human
      synovial fluid. The synovial fluid exosomes share similar characteristics (size,
      surface marker, miRNA content) with previously described exosomes in other body
      fluids. MiRNA microarray analysis showed OA specific exosomal miRNA of male and
      female OA. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis identified gender-specific target genes/signaling
      pathways. These pathway analyses showed that female OA specific miRNAs are
      estrogen responsive and target TLR (toll-like receptor) signaling pathways.
      Furthermore, articular chondrocytes treated with OA derived extracellular
      vesicles had decreased expression of anabolic genes and elevated expression of
      catabolic and inflammatory genes. In conclusion, synovial fluid exosomal miRNA
      content is altered in patients with OA and these changes are gender specific.

PMID- 28515467
TI  - Thermal radiation of Er doped dielectric crystals: Probing the range of
      applicability of the Kirchhoff's law.
AB  - Kirchhoff's law of thermal radiation, relating emissivity and absorptance is
      commonly formulated for opaque bodies in thermodynamic equilibrium with the
      environment. However, in many systems of practical importance, both assumptions
      are often not satisfied. We revisit the century-old law and examine the limits of
      its applicability in an example of Er:YAG and Er:YLF dielectric crystals
      potential radiation converters for thermophotovoltaic applications. The (80 at.%)
      Er:YAG crystal is opaque between 1.45 MUm and 1.64 MUm. In this spectral range,
      its absorptance alpha(lambda) is spectrally flat and differentiates from unity
      only by a small amount of reflection. The shape of the emissivity spectrum
      E(lambda) closely matches that of absorptance alpha(lambda), implying that the
      Kirchhoff's law can adequately describe thermal radiation of opaque bodies, even
      if thermodynamic equilibrium is not satisfied. The (20 at.%) Er:YLF crystal had
      smaller size, lower concentration of Er ions, and it was not opaque.
      Nevertheless, its spectrum of emissivity had almost the same shape (between 1.45
      MUm and 1.62 MUm) as the absorptance derived from the transmission measurements.
      Our results are consistent with the conclusion that the Kirchhoff's law of
      thermal radiation can be extended (with caution) to not-opaque bodies away from
      the thermodynamic equilibrium.

PMID- 28515468
TI  - Cardiolipin content, linoleic acid composition, and tafazzin expression in
      response to skeletal muscle overload and unload stimuli.
AB  - Cardiolipin (CL) is a unique mitochondrial phospholipid that, in skeletal muscle,
      is enriched with linoleic acid (18:2n6). Together, CL content and CL 18:2n6
      composition are critical determinants of mitochondrial function. Skeletal muscle
      is comprised of slow and fast fibers that have high and low mitochondrial
      content, respectively. In response to overloading and unloading stimuli, these
      muscles undergo a fast-to-slow oxidative fiber type shift and a slow-to-fast
      glycolytic fiber type shift, respectively, with a concomitant change in
      mitochondrial content. Here, we examined changes in CL content and CL 18:2n6
      composition under these conditions along with tafazzin (Taz) protein, which is a
      transacylase enzyme that generates CL lipids enriched with 18:2n6. Our results
      show that CL content, CL 18:2n6 composition, and Taz protein content increased
      with an overload stimulus in plantaris. Conversely, CL content and CL 18:2n6
      composition was reduced with an unloaded stimulus in soleus. Interestingly, Taz
      protein was increased in the unloaded soleus, suggesting that Taz may provide
      some form of compensation for decreased CL content and CL 18:2n6 composition.
      Together, this study highlights the dynamic nature of CL and Taz in skeletal
      muscle, and future studies will examine the physiological significance behind the
      changes in CL content, CL 18:2n6 and Taz.

PMID- 28515469
TI  - The Topobiology of Chemical Elements in Seabird Feathers.
AB  - The highly organized morphogenesis of bird feathers holds important phylo- and
      ontogenetic information on the evolution of birds, organogenesis, tissue
      regeneration, and the health status of individual animals. Altered topobiological
      patterns are regularly used as retrospective evidence for disturbed developmental
      trajectories due to the past exposure to environmental stressors. Using the most
      advanced high-resolution (5-70 um) X-ray fluorescence microscopy (XFM), we
      describe in the feathers from three species of Procellariiformes hitherto
      unknown, depositions of elements (Zn, Ca, Br, Cu, Fe) that are independent of
      pigmentation or any underlying variation in density or polymer structure. In the
      case of Zn, the pattern across several species of Procellariiformes, but not
      other species, consisted of highly regular bands of Zn numbering 30-32, which may
      reflect the estimated number of days of active feather growth or the duration of
      the moult period. Thus, speculatively, the highly consistent Zn pattern might be
      the result of a so far unknown diurnal systemic regulation rather than local
      heterogeneity amongst the follicular stem cells.

PMID- 28515470
TI  - A novel missense mutation in the HECT domain of NEDD4L identified in a girl with
      periventricular nodular heterotopia, polymicrogyria and cleft palate.
AB  - We identified a novel de novo heterozygous missense mutation in the NEDD4L gene
      (NM_015277: c.2617G>A; p.Glu873Lys) through whole-exome sequencing in a 3-year
      old girl showing severe global developmental delay, infantile spasms, cleft
      palate, periventricular nodular heterotopia and polymicrogyria. Mutations in the
      HECT domain of NEDD4L have been reported in patients with a neurodevelopmental
      disorder along with similar brain malformations. All patients reported with
      NEDD4L HECT domain mutations showed periventricular nodular heterotopia, and most
      had seizures, cortex anomalies, cleft palate and syndactyly. The unique
      constellation of clinical features in patients with NEDD4L mutations might help
      clinically distinguish them from patients with other genetic mutations including
      FLNA, which is a well-known causative gene of periventricular nodular
      heterotopia. Although mutations in the HECT domain of NEDD4L that lead to AKT
      mTOR pathway deregulation in forced expression system were reported, our western
      blot analysis did not show an increased level of AKT-mTOR activity in
      lymphoblastoid cell lines (LCLs) derived from the patient. In contrast to the
      forced overexpression system, AKT-mTOR pathway deregulation in LCLs derived from
      our patient seems to be subtle.

PMID- 28515472
TI  - Carrier frequency of Wilson's disease in the Korean population: a DNA-based
      approach.
AB  - Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B gene
      mutation. The frequency of WD is about 1 in 30 000 worldwide. In the present
      study, we screened 14 835 dried blood spots (DBSs) from asymptomatic Korean
      neonates and retrospectively reviewed massively parallel sequencing of 1090
      control individuals to estimate carrier frequency. TaqMan real-time PCR assays
      were conducted to detect six mutations that account for 58.3% of mutations in
      Korean WD patients: c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val), c.3086C>T
      (p.Thr1029Ile), c.3247C>T (p.Leu1083Phe), c.3556G>A (p.Gly1186Ser) and c.3809A>G
      (p.Asn1270Ser). We also retrospectively reviewed data from 1090 individuals with
      various indications other than WD for whom whole-exome or panel sequencing data
      were available. Mutant allele frequency based on the six most common mutations
      was 0.0067 among the total of 14 835 DBSs screened. Given that these six
      mutations account for 58.3% of mutations in Korean WD patients, the corrected
      mutant allele frequency is 0.0115 (95% confidence interval (CI): 0.0103-0.0128).
      Corresponding incidence (q2) and carrier frequency (2pq) were estimated to be
      1:7561 and 1:44, respectively. In retrospective data analysis of 1090 control
      individuals, allele frequency of pathogenic or likely pathogenic variants was
      0.0096 (95% CI: 0.0063-0.0146). Corresponding carrier frequency was estimated to
      be 1:53. Estimated allele and carrier frequencies based on DNA screening were
      relatively higher than those reported previously based on clinical ascertainment.

PMID- 28515471
TI  - Clinical and molecular investigation of 14 Japanese patients with complete TFP
      deficiency: a comparison with Caucasian cases.
AB  - Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic
      disorder of mitochondrial fatty-acid oxidation. Isolated long-chain 3-hydroxyacyl
      CoA dehydrogenase deficiency is often reported in Caucasian countries due to a
      common mutation. However, the molecular and clinical basis of complete TFP
      deficiency has not been extensively reported. In this study, 14 Japanese cases
      (13 families) with complete TFP deficiency, including 9 previously reported
      cases, were analyzed to clarify the clinical and molecular characteristics of TFP
      deficiency. The clinical types of the 14 patients were as follows: 12 cases of
      neonatal (n=7) or myopathic (n=5) types and 2 cases of intermediate type.
      Peripheral neuropathy was found in four cases and hypocalcemia due to
      hypoparathyroidism, which is rarely reported in Caucasian patients, had developed
      in four cases. Maternal hemolysis, elevated liver enzymes and low platelet count
      syndrome and acute fatty liver of pregnancy were noted in two and one mothers,
      respectively. Fourteen mutations were identified in 26 alleles in Japanese
      patients, including two novel mutations (HADHA: c.361C>T, and HADHA-HADHB:
      g.26233880_ 26248855del), although no common mutations were found. This study
      suggests that the molecular and clinical aspects of Japanese patients with TFP
      deficiencies differ from those of Caucasian patients.

PMID- 28515473
TI  - Placental O-GlcNAc-transferase expression and interactions with the
      glucocorticoid receptor are sex specific and regulated by maternal corticosterone
      exposure in mice.
AB  - Maternal stress programs offspring disease in a sexually dimorphic manner with
      males often more adversely affected. Previous studies of maternal glucocorticoid
      exposure suggest male vulnerability may derive from placental alterations. The
      hexosamine signalling pathway and O-linked glycosylation (O-GlcNAcylation) are
      part of an essential adaptive survival response in healthy cells. The key enzyme
      involved is O-linked-N-acetylglucosamine transferase (OGT), a gene recently
      identified as a sex-specific placental biomarker of maternal stress. Using a
      mouse model of maternal corticosterone (Cort) exposure, we examined components of
      hexosamine biosynthesis/signalling and O-GlcNAcylation in whole placentae at
      E14.5. Our results demonstrate sex-specific differences in OGT levels and O
      GlcNAcylation during Cort exposure which impacts on key mediators of cell
      survival, in particular AKT as well as the stress responsive OGT/GR
      transrepression complex. In male placentae only, Cort exposure increased Akt O
      GlcNacylation which correlated with decreased phosphorylation. Female placentae
      had higher basal OGT and OGT/GR complex compared with male placentae. Cort
      exposure did not alter these levels in female placentae but increased global O
      GlcNacylation. In male placentae Cort increased OGT and OGT/GR complex with no
      change in global O-GlcNacylation. These findings suggest that sex-specific
      differences in placental OGT play a key role in the sexually dimorphic responses
      to stress.

PMID- 28515475
TI  - Distinguishing physical mechanisms using GISAXS experiments and linear theory:
      the importance of high wavenumbers.
AB  - In this work we analyze GISAXS measurements of the structure factor of Si
      surfaces evolving during 1 keV Ar+ ion bombardment. Using newly-developed methods
      sensitive to the full range of experimentally-available wavenumbers q, we extract
      the linear amplification rate R(q) governing surface stability over a range of
      wavenumbers 4-5 times larger than has previously been obtained. Comparing with
      theoretical models also retaining full wavenumber-dependence, we find an
      excellent fit of the experimental data over the full range of irradiation angles
      and wavenumbers. Moreover, the fitted parameter values represent experimental
      evaluation of the magnitudes of most physical mechanisms currently believed to be
      important to the pattern-formation process. In all cases, the extracted values
      agree well with direct observations or atomistic simulations of the same
      quantities, suggesting that GISAXS analysis may allow more powerful comparison
      between experiment and theory than had previously been thought.

PMID- 28515474
TI  - Blunted Ambiguity Aversion During Cost-Benefit Decisions in Antisocial
      Individuals.
AB  - Antisocial behavior is often assumed to reflect aberrant risk processing.
      However, many of the most significant forms of antisocial behavior, including
      crime, reflect the outcomes of decisions made under conditions of ambiguity
      rather than risk. While risk and ambiguity are formally distinct and
      experimentally dissociable, little is known about ambiguity sensitivity in
      individuals who engage in chronic antisocial behavior. We used a financial
      decision-making task in a high-risk community-based sample to test for
      associations between sensitivity to ambiguity, antisocial behavior, and arrest
      history. Sensitivity to ambiguity was lower in individuals who met diagnostic
      criteria for Antisocial Personality Disorder. Lower ambiguity sensitivity was
      also associated with higher externalizing (but not psychopathy) scores, and with
      higher levels of aggression (but not rule-breaking). Finally, blunted sensitivity
      to ambiguity also predicted a greater frequency of arrests. Together, these data
      suggest that alterations in cost-benefit decision-making under conditions of
      ambiguity may promote antisocial behavior.

PMID- 28515476
TI  - Spin-orbit-torque-induced magnetic domain wall motion in Ta/CoFe nanowires with
      sloped perpendicular magnetic anisotropy.
AB  - In materials with the gradient of magnetic anisotropy, spin-orbit-torque-induced
      magnetization behaviour has attracted attention because of its intriguing
      scientific principle and potential application. Most of the magnetization
      behaviours microscopically originate from magnetic domain wall motion, which can
      be precisely depicted using the standard cooperative coordinate method (CCM).
      However, the domain wall motion in materials with the gradient of magnetic
      anisotropy using the CCM remains lack of investigation. In this paper, by
      adopting CCM, we established a set of equations to quantitatively depict the spin
      orbit-torque-induced motion of domain walls in a Ta/CoFe nanotrack with weak
      Dzyaloshinskii-Moriya interaction and magnetic anisotropy gradient. The equations
      were solved numerically, and the solutions are similar to those of a
      micromagnetic simulation. The results indicate that the enhanced anisotropy along
      the track acts as a barrier to inhibit the motion of the domain wall. In
      contrast, the domain wall can be pushed to move in a direction with reduced
      anisotropy, with the velocity being accelerated by more than twice compared with
      that for the constant anisotropy case. This substantial velocity manipulation by
      anisotropy engineering is important in designing novel magnetic information
      devices with high reading speeds.

PMID- 28515478
TI  - Molecular phylogenetics and biogeography of the mint tribe Elsholtzieae
      (Nepetoideae, Lamiaceae), with an emphasis on its diversification in East Asia.
AB  - Elsholtzia and its allied genera such as Collinsonia and Perilla (tribe
      Elsholtzieae, Lamiaceae) are an ecologically and economically important plant
      group consisting of ~71 species, with most species distributed in East and
      Southeast Asia, and several species in North America. Their phylogeny and
      historical biogeography resulting in a distant intercontinental disjunction are
      poorly understood. Here we use two nuclear (ETS, ITS) and five chloroplast (rbcL,
      matK, trnL-F, ycf1, ycf1-rps15) fragments to reconstruct the phylogeny,
      biogeographic history, and patterns of diversification of Elsholtzieae. The tribe
      Elsholtzieae is monophyletic and divided into five clades. The woody Elsholtzia
      species are nested within herbaceous ones and are inferred to have evolved from
      herbaceous ancestors. Molecular dating shows that the five major clades were
      established during the Eocene period, but most of the modern diversity did not
      originate until the Miocene. The divergence between the New World Collinsonia and
      the Old World Mosla-Keiskea-Perilla clade was dated to the mid-Miocene. Ancestral
      area reconstructions suggest that the tribe originated in East Asia, and then
      dispersed to Southeast Asia and North America. Overall, our findings highlight
      the important roles of the uplifts of the Qinghai-Tibetan Plateau (QTP) and
      climate changes from Middle Miocene onwards in promoting species diversification
      of Elsholtzieae.

PMID- 28515477
TI  - Cancer cachexia associates with a systemic autophagy-inducing activity mimicked
      by cancer cell-derived IL-6 trans-signaling.
AB  - The majority of cancer patients with advanced disease experience weight loss,
      including loss of lean body mass. Severe weight loss is characteristic for cancer
      cachexia, a condition that significantly impairs functional status and survival.
      The underlying causes of cachexia are incompletely understood, and currently no
      therapeutic approach can completely reverse the condition. Autophagy coordinates
      lysosomal destruction of cytosolic constituents and is systemically induced by
      starvation. We hypothesized that starvation-mimicking signaling compounds
      secreted from tumor cells may cause a systemic acceleration of autophagy during
      cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in
      myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung
      cancer patients, were cachexia is prevalent, there was a significant correlation
      between elevated IL-6 expression in the tumor and poor prognosis of the patients.
      We found evidence for an autophagy-inducing bioactivity in serum from cancer
      patients and that this is clearly associated with weight loss. Importantly, the
      autophagy-inducing bioactivity was reduced by interference with IL-6 trans
      signaling. Together, our findings suggest that IL-6 trans-signaling may be
      targeted in cancer cachexia.

PMID- 28515479
TI  - Acquisition of virulence factors in livestock-associated MRSA: Lysogenic
      conversion of CC398 strains by virulence gene-containing phages.
AB  - Staphylococcus aureus MRSA strains belonging to the clonal complex 398 (CC398)
      are highly prevalent in livestock and companion animals but may also cause
      serious infections in humans. CC398 strains in livestock usually do not possess
      well-known virulence factors that can be frequently found in other MRSA sequence
      types (ST). Since many staphylococcal virulence genes are residing on the genomes
      of temperate phages, the question arises why livestock-associated (LA-) CC398
      strains are only rarely infected by those phages. We isolated and characterized
      four temperate phages (P240, P282, P630 and P1105) containing genes of the immune
      evasion cluster (IEC) and/or for the Panton-Valentine leucocidin (PVL). Sequence
      analysis of the phage genomes showed that they are closely related to known
      phages and that the DNA region encoding lysis proteins, virulence factors and the
      integrase exhibits numerous DNA repeats which may facilitate genomic
      rearrangements. All phages lysed and lysogenized LA-CC398 strains. Integration of
      IEC phage P282 was detected at ten sites of the hosts' chromosome. The prophages
      were stably inherited in LA-CC398 and enterotoxin A, staphylokinase and PVL toxin
      were produced. The data demonstrate that lysogenic conversion of LA-CC398 strains
      by virulence-associated phages may occur and that new pathotypes may emerge by
      this mechanism.

PMID- 28515480
TI  - Weak stromal Caveolin-1 expression in colorectal liver metastases predicts poor
      prognosis after hepatectomy for liver-only colorectal metastases.
AB  - Loss of stromal Caveolin-1 (CAV1) expression is associated with poor prognosis in
      various cancers. We evaluated the prognostic value of CAV1 expression of both
      cancer cells and stromal cells in colorectal liver metastases (CRLM) in patients
      undergoing hepatectomy. In this retrospective study, 109 patients were enrolled.
      CAV1 expression was studied by immunohistochemistry. The staining was scored
      semiquantitatively as weak or strong. Disease-free survival (DFS) and overall
      survival (OS) were calculated using both Kaplan-Meier and multivariate
      Coxregression methods. Weak stromal CAV1 expression was associated with decreased
      DFS and OS in univariate and in multivariate analysis (HR 2.00; 95% CI, 1.24
      3.22; P = 0.004, and HR 2.47; 95% CI, 1.28-4.76; P = 0.007, respectively). Cancer
      cell CAV1 expression was not associated with DFS and OS. Five-year DFS and OS
      rates were 13% and 43%, respectively, in patients with weak stromal CAV1
      expression and 40% and 71%, respectively, in patients with strong stromal CAV1
      expression. In this study, we indicate that weak stromal CAV1 expression in CRLM
      is an adverse prognostic factor in patients who undergo liver resection for liver
      only colorectal metastases. We suggest validation of this finding in an
      independent cohort and consideration of risk stratification for post-hepatectomy
      adjuvant follow-up and therapy.

PMID- 28515482
TI  - Precise and diffraction-limited waveguide-to-free-space focusing gratings.
AB  - We present the design and characterization of waveguide grating devices that
      couple visible-wavelength light at lambda = 674 nm from single-mode, high index
      contrast dielectric waveguides to free-space beams forming micron-scale
      diffraction-limited spots a designed distance and angle from the grating. With a
      view to application in spatially-selective optical addressing, and in contrast to
      previous work on similar devices, deviations from the main Gaussian lobe up to 25
      microns from the focus and down to the 5 * 10-6 level in relative intensity are
      characterized as well; we show that along one dimension the intensity of these
      weak sidelobes approaches the limit imposed by diffraction from the finite field
      extent in the grating region. Additionally, we characterize the polarization
      purity in the focal region, observing at the center of the focus a low impurity
      <3 * 10-4 in relative intensity. Our approach allows quick, intuitive design of
      devices with such performance, which may be applied in trapped-ion quantum
      information processing and generally in any systems requiring optical routing to
      or from objects 10 s-100 s of microns from a chip surface, but benefitting from
      the parallelism and density of planar-fabricated dielectric integrated optics.

PMID- 28515481
TI  - Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat
      Promoter of Lentiviruses.
AB  - G-quadruplexes (G4s) are secondary structures of nucleic acids that
      epigenetically regulate cellular processes. In the human immunodeficiency
      lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter.
      Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4
      ligands intensifies this effect. Cellular proteins modulate viral transcription
      by inducing/unfolding LTR G4s. We here expanded our investigation on the presence
      of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely
      conserved in primate lentiviruses. A G4 was also present in a cattle-infecting
      lentivirus. All other non-primate lentiviruses displayed hints of less stable
      G4s. In primate lentiviruses, the possibility to fold into G4s was highly
      conserved among strains. LTR G4 sequences were very similar among
      phylogenetically related primate viruses, while they increasingly differed in
      viruses that diverged early from a common ancestor. A strong correlation between
      primate lentivirus LTR G4s and Sp1/NFkappaB binding sites was found. All LTR G4s
      folded: their complexity was assessed by polymerase stop assay. Our data support
      a role of the lentiviruses 5'-LTR G4 region as control centre of viral
      transcription, where folding/unfolding of G4s and multiple recruitment of factors
      based on both sequence and structure may take place.

PMID- 28515483
TI  - Refuges and host shift pathways of host-specialized aphids Aphis gossypii.
AB  - Polyphagous cotton-melon aphid populations usually comprise cotton- and cucurbit
      specialized biotypes. Host-specialized aphids are prone to food shortages.
      Cucumber, the favourite food of cucurbit-specialized aphids, is usually absent
      during autumn and winter in Nanjing, China. Therefore, suboptimal host plants act
      as refuges and govern the population dynamics of this aphid. The species, growth
      stages and leaf ages of host plants that cotton- and cucurbit-specialized aphids
      potentially could use were explored in this study. Cotton-specialized aphids were
      found to use wild chrysanthemum, potato, zucchini, pumpkin and flowering cucumber
      besides cotton, whilst cucurbit-specialized aphids were able to utilize potato,
      zucchini, pumpkin and mature cotton besides cucumber. The population dynamics and
      genotype frequencies of aphids on hibiscus, cotton, zucchini, cucumber and
      pumpkin showed that cotton-melon aphids on cucumber could transfer onto mature
      cotton. Aphids on zucchini shared microsatellite genotypes with aphids on cotton
      and cucumber. The predominant genotype of aphids on cotton was found on hibiscus,
      but the predominant genotype on cucumber was not found on hibiscus. Host
      specialized aphids clearly have refuges during food shortages. Hibiscus is an
      overwintering host for cotton-specialized aphids but not for cucurbit-aphids.
      Removing refuges or managing aphids on refuges could potentially be an effective
      method to control cotton-melon aphids.

PMID- 28515484
TI  - The complex tibial organ of the New Zealand ground weta: sensory adaptations for
      vibrational signal detection.
AB  - In orthopteran insects, a complex tibial organ has evolved to detect substrate
      vibrations and/or airborne sound. Species of New Zealand weta (Anostostomatidae)
      with tympanal ears on the foreleg tibia use this organ to communicate by sound,
      while in atympanate species (which communicate by substrate drumming) the organ
      is unstudied. We investigated the complex tibial organ of the atympanate ground
      weta, Hemiandrus pallitarsis, for vibration detection adaptations. This system
      contains four sensory components (subgenual organ, intermediate organ, crista
      acustica homolog, accessory organ) in all legs, together with up to 90
      scolopidial sensilla. Microcomputed tomography shows that the subgenual organ
      spans the hemolymph channel, with attachments suggesting that hemolymph
      oscillations displace the organ in a hinged-plate fashion. Subgenual sensilla are
      likely excited by substrate oscillations transmitted within the leg. Instead of
      the usual suspension within the middle of the tibial cavity, we show that the
      intermediate organ and crista acustica homolog comprise a cellular mass broadly
      attached to the anterior tibial wall. They likely detect cuticular vibrations,
      and not airborne sound. This atympanate complex tibial organ shows elaborate
      structural changes suggesting detection of vibrational stimuli by parallel input
      pathways, thus correlating well with the burrowing lifestyle and communication by
      substrate-transmitted vibration.

PMID- 28515485
TI  - E-cigarettes induce toxicological effects that can raise the cancer risk.
AB  - Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a
      vaping solution rather than smoke and without tobacco combustion. Perceived as a
      safer alternative to conventional cigarettes, e-cigs are aggressively marketed as
      lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory
      guidelines. E-cigs have also gained popularity among never-smokers and teenagers,
      becoming an emergent public health issue. Despite the burgeoning worldwide
      consumption of e-cigs, their safety remains largely unproven and it is unknown
      whether these devices cause in vivo toxicological effects that could contribute
      to cancer. Here we demonstrate the co-mutagenic and cancer-initiating effects of
      e-cig vapour in a rat lung model. We found that e-cigs have a powerful booster
      effect on phase-I carcinogen-bioactivating enzymes, including activators of
      polycyclic aromatic hydrocarbons (PAHs), and increase oxygen free radical
      production and DNA oxidation to 8-hydroxy-2'-deoxyguanosine. Furthermore, we
      found that e-cigs damage DNA not only at chromosomal level in peripheral blood,
      such as strand breaks in leucocytes and micronuclei formation in reticulocytes,
      but also at gene level such as point mutations in urine. Our results demonstrate
      that exposure to e-cigs could endanger human health, particularly among younger
      more vulnerable consumers.

PMID- 28515486
TI  - Prognostic significance of TCF21 mRNA expression in patients with lung
      adenocarcinoma.
AB  - Several prognostic indicators have shown inconsistencies in patients of different
      genders with lung adenocarcinoma, indicating that these variations may be due to
      the different genetic background of males and females with lung adenocarcinoma.
      In this study, we first used the Gene-Cloud of Biotechnology Information (GCBI)
      bioinformatics platform to identify differentially expressed genes (DEGs) that
      eliminated gender differences between lung adenocarcinoma and normal lung
      tissues. Then, we screened out that transcription factor 21 (TCF21) is a hub gene
      among these DEGs by creating a gene co-expression network on the GCBI platform.
      Furthermore, we used the comprehensive survival analysis platforms Kaplan-Meier
      plotter and PrognoScan to assess the prognostic value of TCF21 expression in lung
      adenocarcinoma patients. Finally, we concluded that decreased mRNA expression of
      TCF21 is a predictor for poor prognosis in patients with lung adenocarcinoma.

PMID- 28515488
TI  - Learning and memory: A state to remember.

PMID- 28515487
TI  - Functional interaction between FUS and SMN underlies SMA-like splicing changes in
      wild-type hFUS mice.
AB  - Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS)
      point to dysfunction in RNA processing as a major pathogenic mechanism. However,
      whether a precise RNA pathway is particularly affected remains unknown. Evidence
      suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor
      in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e.
      regulation of alternative splicing, and that disturbances in SMN-regulated
      functions, either caused by depletion of SMN protein (as in the case of SMA) or
      by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a
      common theme in both diseases. In this work, we followed these leads and tested
      their pathogenic relevance in vivo. FUS-associated ALS recapitulates, in
      transgenic mice, crucial molecular features that characterise mouse models of
      SMA, including defects in snRNPs distribution and in the alternative splicing of
      genes important for motor neurons. Notably, altering SMN levels by
      haploinsufficiency or overexpression does not impact the phenotypes of mouse or
      Drosophila models of FUS-mediated toxicity. Overall, these findings suggest that
      FUS and SMN functionally interact and that FUS may act downstream of SMN
      regulated snRNP assembly in the regulation of alternative splicing and gene
      expression.

PMID- 28515489
TI  - Brain evolution: Genetic layering.

PMID- 28515490
TI  - Neuronal development: The source of the signal.

PMID- 28515493
TI  - Sleep: Dream a little dream.

PMID- 28515494
TI  - Ligand chain length drives activation of lipid G protein-coupled receptors.
AB  - Sphingosine-1-phosphate (S1P) is a lipid mediator that can activate five cell
      membrane G protein-coupled receptors (GPCRs) which carry a variety of essential
      functions and are promising drug targets. S1P is composed of a polar zwitterionic
      head-group and a hydrophobic alkyl chain. This implies an activation mechanism of
      its cognate receptor that must be significantly different from what is known for
      prototypical GPCRs (ie receptor to small hydrophilic ligands). Here we aim to
      identify the structural features responsible for S1P agonism by combining
      molecular dynamics simulations and functional assays using S1P analogs of
      different alkyl chain lengths. We propose that high affinity binding involves
      polar interactions between the lipid head-group and receptor side chains while
      activation is due to hydrophobic interactions between the lipid tail and residues
      in a distinct binding site. We observe that ligand efficacy is directly related
      to alkyl chain length but also varies with receptor subtypes in correlation with
      the size of this binding pocket. Integrating experimental and computational data,
      we propose an activation mechanism for the S1P receptors involving agonist
      induced conformational events that are conserved throughout class A GPCRs.

PMID- 28515491
TI  - The emerging field of epigenetics in neurodegeneration and neuroprotection.
AB  - Epigenetic mechanisms - including DNA methylation, histone post-translational
      modifications and changes in nucleosome positioning - regulate gene expression,
      cellular differentiation and development in almost all tissues, including the
      brain. In adulthood, changes in the epigenome are crucial for higher cognitive
      functions such as learning and memory. Striking new evidence implicates the
      dysregulation of epigenetic mechanisms in neurodegenerative disorders and
      diseases. Although these disorders differ in their underlying causes and
      pathophysiologies, many involve the dysregulation of restrictive element 1
      silencing transcription factor (REST), which acts via epigenetic mechanisms to
      regulate gene expression. Although not somatically heritable, epigenetic
      modifications in neurons are dynamic and reversible, which makes them good
      targets for therapeutic intervention.

PMID- 28515495
TI  - The Failure Envelope Concept Applied To The Bone-Dental Implant System.
AB  - Dental implants interact with the jawbone through their common interface. While
      the implant is an inert structure, the jawbone is a living one that reacts to
      mechanical stimuli. Setting aside mechanical failure considerations of the
      implant, the bone is the main component to be addressed. With most failure
      criteria being expressed in terms of stress or strain values, their fulfillment
      can mean structural flow or fracture. However, in addition to those effects, the
      bony structure is likely to react biologically to the applied loads by
      dissolution or remodeling, so that additional (strain-based) criteria must be
      taken into account. While the literature abounds in studies of particular loading
      configurations, e.g. angle and value of the applied load to the implant, a
      general study of the admissible implant loads is still missing. This paper
      introduces the concept of failure envelopes for the dental implant-jawbone
      system, thereby defining admissible combinations of vertical and lateral loads
      for various failure criteria of the jawbone. Those envelopes are compared in
      terms of conservatism, thereby providing a systematic comparison of the various
      failure criteria and their determination of the admissible loads.

PMID- 28515492
TI  - The brain, sirtuins, and ageing.
AB  - In mammals, recent studies have demonstrated that the brain, the hypothalamus in
      particular, is a key bidirectional integrator of humoral and neural information
      from peripheral tissues, thus influencing ageing both in the brain and at the
      'systemic' level. CNS decline drives the progressive impairment of cognitive,
      social and physical abilities, and the mechanisms underlying CNS regulation of
      the ageing process, such as microglia-neuron networks and the activities of
      sirtuins, a class of NAD+-dependent deacylases, are beginning to be understood.
      Such mechanisms are potential targets for the prevention or treatment of age
      associated dysfunction and for the extension of a healthy lifespan.

PMID- 28515496
TI  - Do Different Methods for Modeling Age-Graded Trajectories Yield Consistent and
      Valid Results?
AB  - Data on age-sequenced trajectories of individuals' attributes are used for a
      growing number of research purposes. However, there is no consensus about which
      method to use to identify the number of discrete trajectories in a population or
      to assign individuals to a specific trajectory group. We modeled real and
      simulated trajectory data using "naive" methods, optimal matching, grade of
      membership models, and three types of finite mixture models. We found that these
      methods produced inferences about the number of trajectories that frequently
      differ (1) from one another and (2) from the truth as represented by simulation
      parameters. We also found that they differed in the assignment of individuals to
      trajectory groups. In light of these findings, we argue that researchers should
      interpret results based on these methods cautiously, neither reifying point
      estimates about the number of trajectories nor treating individuals' trajectory
      group assignments as certain.

PMID- 28515498
TI  - Using Lean to Develop Frontline Clinical Staff Pharmacists as Residency Program
      Primary Preceptors.

PMID- 28515499
TI  - Comment on Tapentadol and Serotonin Syndrome.

PMID- 28515497
TI  - Invasion dynamics of Asian hornet, Vespa velutina (Hymenoptera: Vespidae): a case
      study of a commune in south-west France.
AB  - Asian hornet, Vespa velutina Lepeletier nests were discovered in 2007 in Andernos
      les-Bains on the south-west coast of France, 3 years after the first reported
      sightings in France. The number of nests increased in the commune over the
      following 7 years, despite local authorities enacting a destruction policy. The
      nests existed in close proximity to one another leading to a high density of over
      10 nests per square kilometre in urban areas. New information on the chosen
      habitat for nests is presented, and the differences between primary and secondary
      locations are evident, with primary nests mostly occupying buildings and man-made
      structures, while secondary nests were found on trees. Using Bayesian inference
      methods, we fit a basic model to the observational data, which allows us to
      estimate key demographic parameters. This model fit is highly informative for
      predicting V. velutina spread and colonisation of other at-risk regions, and
      suggests that local control has a limited impact on the spread of V. velutina
      once established within a region.

PMID- 28515500
TI  - Comment on "Probable Tapentadol-Associated Serotonin Syndrome After Overdose".

PMID- 28515501
TI  - ISMP Medication Error Report Analysis: Potential Issues with New Basal
      Insulin/GLP-1 Fixed Combinations Hydroxyzine-Hydroxyurea Mix-up Concomitant Use
      of Entresto and ACE Inhibitors Can Lead to Serious Outcomes More Outpatient Oral
      Cancer Drugs Should Be in Blister Packs.
AB  - These medication errors have occurred in health care facilities at least once.
      They will happen again-perhaps where you work. Through education and alertness of
      personnel and procedural safeguards, they can be avoided. You should consider
      publishing accounts of errors in your newsletters and/or presenting them at your
      inservice training programs. Your assistance is required to continue this
      feature. The reports described here were received through the Institute for Safe
      Medication Practices (ISMP) Medication Errors Reporting Program. Any reports
      published by ISMP will be anonymous. Comments are also invited; the writers'
      names will be published if desired. ISMP may be contacted at the address shown
      below. Errors, close calls, or hazardous conditions may be reported directly to
      ISMP through the ISMP Web site (www.ismp.org, by calling 800-FAIL-SAFE, or via e
      mail at ismpinfo@ismp.org. ISMP guarantees the confidentiality and security of
      the information received and respects reporters' wishes as to the level of detail
      included in publications.

PMID- 28515502
TI  - ISMP Adverse Drug Reactions: Pregabalin-Induced Stuttering Nitroglycerine-Induced
      Bradycardia Progressing to Asystole Minocycline-Induced DRESS Leading to Liver
      Transplantation and Type 1 Diabetes Increased Risk of Vertebral Fractures in
      Women Receiving Thiazide or Loop Diuretics Gambling Disorder and Impulse Control
      Disorder with Aripiprazole.
AB  - The purpose of this feature is to heighten awareness of specific adverse drug
      reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to
      the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If
      you have reported an interesting, preventable ADR to MedWatch, please consider
      sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside
      Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail:
      mmancano@temple.edu). Your report will be published anonymously unless otherwise
      requested. This feature is provided by the Institute for Safe Medication
      Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple
      University School of Pharmacy. ISMP is an FDA MedWatch partner.

PMID- 28515503
TI  - Drug Monographs: Olaratumab and Rucaparib.
AB  - The complexity of cancer chemotherapy requires pharmacists be familiar with the
      complicated regimens and highly toxic agents used. This column reviews various
      issues related to preparation, dispensing, and administration of antineoplastic
      therapy, and the agents, both commercially available and investigational, used to
      treat malignant diseases. Questions or suggestions for topics should be addressed
      to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201
      Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J.
      Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology
      Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander
      Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The information
      presented in this review is based on published data and clinical expertise and
      includes information not included in the product labeling. Incorporation of such
      published data provides a more robust assessment of the drugs and assists
      pharmacists in evaluation of orders for off-label use of these agents.

PMID- 28515504
TI  - 21st Century Cures Act.

PMID- 28515505
TI  - Application of the Layered Learning Practice Model in an Academic Medical Center.
AB  - The layered learning practice model (LLPM) is a teaching strategy designed to
      train residents to precept students and other residents with the oversight of a
      seasoned clinical pharmacist. This model serves as a tool for residency programs
      to implement quality precepting opportunities and learning experiences as they
      look for new ways to integrate multiple learners into the practice setting. The
      levels of the LLPM include a senior preceptor, resident, and student. It is best
      implemented through utilization of 4 steps: orientation to the LLPM,
      preexperience planning, implementation, and postexperience evaluation.
      Orientation introduces preceptors and residents to the LLPM and outlines
      expectations for each precepting level. Preexperience planning allows the
      resident to take a leadership role in developing calendars, rotation activities,
      rubrics, and activities that match goals and objectives. For implementation, the
      senior preceptor maintains an active role with all learners; the resident serves
      as the student's primary preceptor and is responsible for incorporating the
      student into clinical activities, evaluating student work, and providing
      feedback. Postexperience evaluation is designed to solicit and provide feedback
      to the resident and student and to identify recommendations for improvement of
      the LLPM. Overall, the LLPM is a multilayered model incorporating the expertise
      and unique learning positions of the senior preceptor, resident, and student.
      Redistributing components of the senior preceptor's responsibility amongst
      learners may result in expansion of patient care and clinical services and help
      satisfy the increasing demands placed on pharmacists.

PMID- 28515506
TI  - Impact of Pharmacy Practice Model Expansion on Pharmacokinetic Services:
      Optimization of Vancomycin Dosing and Improved Patient Safety.
AB  - Background: The impact of pharmacy interventions on optimizing vancomycin therapy
      has been described, however interventions vary among studies and the most optimal
      pharmacy practice model (PPM) for pharmacokinetic (PK) services has not been
      established. Objective: The purpose of this study is to demonstrate the value of
      24 hours a day, 7 days a week (24/7) PK services. Methods: New PK services were
      implemented in 2 phases with institutional PPM expansion. Phase 1 included
      universal monitoring by pharmacists with recommendations made to prescribers
      during business hours. Phase 2 expanded clinical pharmacists' coverage to 24/7
      and provided an optional 24/7 pharmacist-managed PK consult service. We compared
      vancomycin therapeutic trough attainment, dosing, and clinical and safety
      outcomes between phases 1 and 2 in adult inpatients receiving therapeutic
      intravenous vancomycin. Results. One hundred and fifty patients were included in
      each phase. Phase 2 had a greater proportion of vancomycin courses with
      therapeutic initial trough concentrations (27.5% vs 46.1%; p = 0.002), higher
      initial trough concentrations (10.9 mcg/mL vs 16.4 mcg/mL; p < 0.001), and
      optimized initial vancomycin dosing (13.5 mg/kg vs 16.2 mg/kg; p < 0.001). Phase
      2 also saw significant reduction in the incidence of vancomycin-associated
      nephrotoxicity (21.1% vs 11.7%; p = 0.038). Dose optimization and improvement in
      initial target trough attainment were most notable among intensive care unit
      (ICU) patients. Conclusions. Our study demonstrated that 24/7 PK services
      implemented with institutional PPM expansion optimized vancomycin target trough
      attainment and improved patient safety.

PMID- 28515507
TI  - Implementing a Tech-Check-Tech Program at a University Health System.
AB  - Background: Tech-Check-Tech (TCT) allows a pharmacy technician to perform the
      final check of medications prepared by another technician. The effect of a TCT
      program on the time required to process medications in a hospital pharmacy has
      not been previously reported. Objective: To evaluate the effect of implementing a
      TCT program on the time required to prepare, check, and deliver medications to
      automated medication supply systems (AMSS) located throughout an academic medical
      center. Methods: The primary outcome was the difference in mean total time
      required to process AMSS medications between pre- and post-implementation
      periods. Forty-five days pre-TCT implementation was compared to 45 days post
      implementation. To assess the effect of the TCT program on pharmacist-time
      allocation, median times required to verify stat and routine medication orders in
      the computerized physician order entry (CPOE) system were analyzed. Results: Mean
      total time spent processing AMSS medications was 24.16 +/- 2.98 hours and 16.79
      +/- 2.65 hours for the pre- and post-TCT implementation periods, respectively
      (difference of 7.37 hours; 95% CI, 6.19-8.55 hours; p < 0.0001). Median
      verification times for stat medication orders were 5 (interquartile range [IQR],
      2-12) minutes before and 4 (IQR, 2-9) minutes after TCT implementation (p <
      0.0001). For routine orders, median verification times were 12 (IQR, 4-30)
      minutes before and 7 (IQR, 3-18) minutes after implementation (p < 0.0001).
      Conclusions: The total time required to process AMSS medications was
      significantly reduced after a TCT program was implemented in an academic medical
      center. Pharmacist medication order verification times were also significantly
      reduced.

PMID- 28515508
TI  - Evaluating Sterility of Single Dose Vials on an Automated Compounding Device.
AB  - Background: Current guidelines for sterile compounding require that single dose
      vials of pharmaceuticals must be discarded after 6 hours when accessed in an ISO
      Class 5 environment. At this time, no studies have evaluated the sterility of
      single dose vials at any time after opening. Objective: The purpose of this study
      is to evaluate the sterility of single dose vials attached to an automated
      compounding device for up to 24 hours and accessed and maintained within a
      cleanroom environment. Methods: This is a prospective, observational study
      evaluating the sterility of 32 pooled samples of manufactured single dose
      injectable drugs attached to an automated compounding device for up to 24 hours
      and maintained within an ISO Class 5 environment in an ISO Class 7 buffer area.
      Each pooled sample was comprised of the remaining contents of 10 single dose vial
      additives that were used for total parenteral nutrition (TPN) and attached to the
      compounder within the previous 24 hours. Samples were evaluated using membrane
      filtration sterility testing and incubated for 14 days per USP <71> requirements.
      Results: The results revealed zero failed sterility samples. Single dose vials
      remained attached to the compounder for an average of 23.8 hours (+/-0.1 hours).
      The average volume per sample was 879 mL (+/-105.1 mL). Manipulation of vials
      during the compounding process included an average of 20.4 manipulations (+/
      1.4). Conclusions: Single dose injectable drugs attached to an automated
      compounding device within an ISO Class 5 cleanroom environment may remain sterile
      for up to 24 hours. Future studies are needed with a larger sample size and under
      continued dynamic working conditions to provide further evidence to extend the
      beyond use date within USP <797>.

PMID- 28515510
TI  - Eteplirsen.
AB  - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well
      documented monographs on drugs that are newly released or are in late phase 3
      trials. The monographs are targeted to Pharmacy & Therapeutics Committees.
      Subscribers also receive monthly 1-page summary monographs on agents that are
      useful for agendas and pharmacy/nursing in-services. A comprehensive target drug
      utilization evaluation/medication use evaluation (DUE/MUE) is also provided each
      month. With a subscription, the monographs are available online to subscribers.
      Monographs can be customized to meet the needs of a facility. Through the
      cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in
      this column. For more information about The Formulary Monograph Service, contact
      Wolters Kluwer customer service at 866-397-3433. The April 2017 monograph topics
      are deflazacort, plecanatide, delafloxacin, oxymetazoline hydrochloride 1% cream,
      and betrixaban. The DUE is on plecanatide.

PMID- 28515509
TI  - Anti-Nuclear Cytoplasmic Antibody-Associated Vasculitis: A Probable Adverse
      Effect of Sofosbuvir Treatment in Chronic Hepatitis C Patients.
AB  - Background: Egypt has the largest hepatitis C virus (HCV) epidemic worldwide.
      Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase.
      It has shown high efficacy in combination with several other drugs and has a low
      reported rate of side effects. Objective: The aim of this prospective cohort
      study was to assess the safety of sofosbuvir-based treatment regimens used to
      treat chronic hepatitis C infections and to detect any side effects of sofosbuvir
      not previously reported. Methods: We studied treatment side effects in 3,000
      patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24
      weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple
      therapy for 12 weeks. The endpoint of the study was the end of treatment.
      Results: Hyperbilirubinemia occurred frequently during treatment in both groups.
      Treatment was discontinued in 72 cases due to hepatic decompensation and drug
      complications; 8 of the cases had deep vein thrombosis (DVT) and 7 had cerebral
      ischemia. Surprisingly, 177/3,000 (5.9%) patients presented with abnormal
      bleeding, 85 of whom had a vasculitic skin rash. Conclusion: We report the
      occurrence of previously nonrecorded side effects with sofosbuvir, namely DVT and
      bleeding disorders associated with anti-nuclear cytoplasmic antibody (ANCA)
      associated vasculitis (AAV).We believe this to be the first report of sofosbuvir
      induced AAV skin lesions and bleeding disorders.

PMID- 28515511
TI  - Approvals, Submission, and Important Labeling Changes for US Marketed
      Pharmaceuticals.
AB  - This monthly feature will help readers keep current on new drug, new indications,
      dosage forms and safety-related changes in labeling or use. Efforts have been
      made to assure the accuracy of this information; however, if there are any
      questions, please let us know at jgeneral@ku.edu.

PMID- 28515513
TI  - Hospital Participation in Prescription Drug Monitoring Programs.
AB  - The prescription drug abuse epidemic continues to grow. This multifaceted problem
      requires a multifaceted solution. In this installment, we discuss prescription
      drug monitoring programs and their relevance to hospital pharmacies.

PMID- 28515512
TI  - A Just Culture Approach to Managing Medication Errors.
AB  - Medication errors continue to be a concern of health care providers and the
      public, in particular how to prevent harm from medication mistakes. Many health
      care workers are afraid to report errors for fear of retribution including the
      loss of professional licensure and even imprisonment. Most health care workers
      are silent, instead of admitting their mistake and discussing it openly with
      peers. This can result in further patient harm if the system causing the mistake
      is not identified and fixed; thus self-denial may have a negative impact on
      patient care outcomes. As a result, pharmacy leaders, in collaboration with
      others, must put systems in place that serve to prevent medication errors while
      promoting a "Just Culture" way of managing performance and outcomes. This culture
      must exist across disciplines and departments. Pharmacy leaders need to
      understand how to classify behaviors associated with errors, set realistic
      expectations, instill values for staff, and promote accountability within the
      workplace. This article reviews the concept of Just Culture and provides ways
      that pharmacy directors can use this concept to manage the degree of error in
      patient-centered pharmacy services.

PMID- 28515514
TI  - 'Advances in understanding and management in obstetric anaesthesia': The great
      myth of our times.

PMID- 28515515
TI  - The parturient in the interventional radiology suite: New frontier in obstetric
      anaesthesia.
AB  - The anaesthesiologist's presence during interventional radiology (IR) is
      increasing due to increasingly ill patients and intricate procedures. The
      management of a parturient in IR suite is complex in terms of logistics of an
      unfamiliar procedure in an unfamiliar area. The literature available is largely
      written by radiologists with little attention paid to anaesthetic details and
      considerations. In the Indian scenario, in the absence of hybrid operating rooms
      (ORs), logistics involve transport of a parturient back and forth between the IR
      suite and the OR. As members of a multidisciplinary team, anaesthesiologists
      should utilise their expertise in fluid management, transfusion therapy and
      critical care to prevent and treat catastrophic events that may accompany severe
      peri-partum bleeding. Ensuring familiarity with the variety of IR procedures and
      the peri-procedure requirements can help the anaesthesiologist provide optimum
      care in the IR suite.

PMID- 28515516
TI  - Changes in cardiac index during labour analgesia: A double-blind randomised
      controlled trial of epidural versus combined spinal epidural analgesia - A
      preliminary study.
AB  - BACKGROUND AND AIMS: Combined spinal-epidural (CSE) analgesia for labour and
      delivery is occasionally associated with foetal bradycardia. Decreases in cardiac
      index (CI) and/or uterine hypertonia are implicated as possible aetiological
      factors. No study has evaluated CI changes following combined spinal analgesia
      for labour and delivery. This prospective, double-blind, randomised controlled
      trial evaluates haemodynamic trends during CSE and epidural analgesia for labour.
      METHODS: Twenty-six parturients at term requesting labour analgesia were
      randomised to receive either epidural (E) or CSE analgesia. The Electrical
      Cardiometry Monitor ICON(r) was used to continuously determine maternal CI non
      invasively, heart rate (HR) and stroke volume at baseline and up to 60 min after
      initiation of either intrathecal or epidural analgesia. In addition, maternal
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded.
      RESULTS: Both SBP and DBP had a similar, significant decrease following
      initiation of either epidural or CSE analgesia. However, parturients in the CSE
      group (n = 10) demonstrated a significant decrease in HR and CI compared to the
      baseline measurements. On the other hand, the parturients in the E (n = 13) group
      showed no decreases in either maternal HR or CI. Foetal heart changes were
      observed in four patients following CSE and one patient following an epidural.
      CONCLUSION: Labour analgesia with CSE is associated with a significant decrease
      in HR and CI when compared to labour analgesia with epidural analgesia. Further
      studies are necessary to determine whether a decrease in CI diminishes placental
      blood flow.

PMID- 28515517
TI  - A clinical comparison between 0.5% levobupivacaine and 0.5% levobupivacaine with
      dexamethasone 8 mg combination in brachial plexus block by the supraclavicular
      approach.
AB  - BACKGROUND AND AIMS: Dexamethasone as an adjuvant to bupivacaine for
      supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade.
      However, the effect of dexamethasone (8 mg) when added to levobupivacaine has not
      been well studied. This study was conducted to find out analgesic efficacy of
      dexamethasone as adjuvant to levobupivacaine in SCBP block. METHODS: Ultrasound-
      guided SCBP block was given to sixty patients, randomly assigned into two groups.
      Group S (thirty patients) received 2 mL normal saline with 25 mL levobupivacaine
      (0.5%) and Group D (thirty patients) received 2 mL of dexamethasone (8 mg) with
      25 mL of levobupivacaine (0.5%), respectively. Time for the first rescue
      analgesia, number of rescue analgesics required in 24 h and different block
      characteristics was assessed. Chi-square test and Student's t-test were used for
      statistical analysis. RESULTS: Time for request of the first rescue analgesia was
      396.13 +/- 109.42 min in Group S and 705.80 +/- 121.46 min in Group D (P <
      0.001). The requirement for rescue analgesics was more in Group S when compared
      to Group D. The onset of sensory and motor block was faster in Group D when
      compared to Group S. The mean duration of sensory and motor block was
      significantly longer in Group D than Group S. CONCLUSION: The addition of
      dexamethasone to levobupivacaine in SCBP blockade prolonged time for first rescue
      analgesia and reduced the requirement of rescue analgesics with faster onset and
      prolonged duration of sensory and motor block.

PMID- 28515519
TI  - Desflurane for ambulatory anaesthesia: A comparison with sevoflurane for recovery
      profile and airway responses.
AB  - BACKGROUND AND AIMS: Desflurane and sevoflurane have low blood gas solubility co
      efficients, allowing a rapid awakening from anaesthesia. However, desfluraneis
      pungent and may cause airway irritability. We compared desflurane and sevoflurane
      with respect to recovery and occurrence of adverse airway responses in
      spontaneously breathing patients while using the ProSealTM laryngeal mask airway
      (LMA). METHODS: Ninety-four adult patients undergoing hysteroscopic procedures
      were divided into sevoflurane (S) group or desflurane (D) group. Patients were
      premedicated with midazolam 0.03 mg/kg and fentanyl 1MUg/kg. Anaesthesia was
      induced with propofol 2.0-2.5 mg/kg, followed by insertion of a ProSealTM LMA.
      Adverse airway responses such as cough, hiccups, laryngospasm and breathholding
      were recorded. In the post-operative period: time to awakening, response to
      verbal commands, orientation, ability to sit with support and the recovery room
      Aldrete score were recorded. RESULTS: Three patients in group S (6.4%) and six
      patients (13.3%) in Group D had adverse airway events. The mean time to eye
      opening (Group S-10.75 +/- 7.54 min, Group D-4.94 +/- 1.74 min), obeying verbal
      commands (Group S-13.13 +/- 8.75 min, Group D-6.55 +/- 1.75 min), orientation
      (Group S-15.42 +/- 8.46 min, Group D-6.23 +/- 2.4 min) and to sit with support
      (Group S-36.09 +/- 12.68 min, Group D-14.35 +/- 3.75 min) were found to be lesser
      with desflurane than with sevoflurane (P < 0.001). The mean time to recovery was
      delayed in Group S-46.00 +/- 12.86 min compared to Group D-26.44 +/- 5.33 min (P
      < 0.001). CONCLUSION: Desflurane has faster awakening properties than sevoflurane
      without an increase in adverse airway events when used during spontaneous
      ventilation through a ProSealTM LMA along with propofol and fentanyl.

PMID- 28515518
TI  - Is segmental epidural anaesthesia an optimal technique for patients undergoing
      percutaneous nephrolithotomy?
AB  - BACKGROUND AND AIMS: Neuraxial anaesthesia has recently become popular for
      percutaneous nephrolithotomy (PCNL). We conducted a study comparing general
      anaesthesia (GA) with segmental (T6-T12) epidural anaesthesia (SEA) for PCNL with
      respect to anaesthesia and surgical characteristics. METHODS: Ninety American
      Society of Anesthesiologists Physical Status-I and II patients undergoing PCNL
      randomly received either GA or SEA. Overall patient satisfaction was the primary
      end point. Intraoperative haemodynamics, epidural block characteristics, post
      operative pain, time to rescue analgesic, total analgesic consumption, discharge
      times from post-anaesthesia care unit, surgeon satisfaction scores and stone
      clearance were secondary end points. Parametric data were analysed by Student's t
      test while non-parametric data were compared with Mann-Whitney U-test. RESULTS:
      Group SEA reported better patient satisfaction (P = 0.005). Patients in group GA
      had significantly higher heart rates (P = 0.0001) and comparable mean arterial
      pressures (P = 0.24). Postoperatively, time to first rescue analgesic and total
      tramadol consumption was higher in Group GA (P = 0.001). Group SEA had lower pain
      scores (P = 0.001). Time to reach Aldrete's score of 9 was shorter in group SEA
      (P = 0.0001). The incidence of nausea was higher in group GA (P = 0.001);
      vomiting rates were comparable (P = 0.15). One patient in group SEA developed
      bradycardia which was successfully treated. Eight patients (18%) had hypertensive
      episodes in group GA versus none in group SEA (P = 0.0001). One patient in GA
      group had pleural injury and was managed with intercostal drain. Stone clearance
      and post-operative haemoglobin levels were comparable in both groups. CONCLUSION:
      PCNL under SEA has a role in selected patients, for short duration surgery and in
      expert hands.

PMID- 28515520
TI  - A comparative evaluation of Video Stylet and flexible fibre-optic bronchoscope in
      the performance of intubation in adult patients.
AB  - BACKGROUND AND AIMS: Video Stylet (VS) is a new intubating modality that provides
      real-time video of endotracheal intubation (ETI). This device does not need
      alignment of the oral, pharyngeal and tracheal axes to view glottis and can be
      used in patients with limited mouth opening. The aim of this study was to compare
      flexible fibre-optic (FO) bronchoscope with VS in elective surgical patients in
      apparently normal airway patients requiring oral ETI. METHODS: Sixty patients
      undergoing elective surgery under general anaesthesia of age group 20-60 years,
      weight 40-70 kg, American Society of Anesthesiologist 1 and 2 and modified
      Mallampatti I and II were included in the study. Patients in group FO (n = 30)
      were intubated by flexible FO bronchoscope, whereas patients in group VS (n = 30)
      were intubated by VS. Primary outcome measure was time taken for intubation
      (TTI). Secondary outcome measures were successful intubation, haemodynamic
      response and post-operative complications if any. RESULTS: Average TTI in cases
      of FO group was 38.2 s (95% confidence interval [CI] 36-41) and in VS group was
      19.7 s (95% CI 19-21; P = 0.0001). Three patients required a second attempt for
      successful intubation in FO group compared to eight in VS group (P = 0.2), with
      no failures in any group. Haemodynamic response and complications rate were
      greater in VS group; however, the differences were not statistically significant.
      CONCLUSION: VS takes lesser time to intubate than flexible FO bronchoscope.

PMID- 28515522
TI  - Comparison of AirtraqTM, McCoyTM and Macintosh laryngoscopes for endotracheal
      intubation in patients with cervical spine immobilisation: A randomised clinical
      trial.
AB  - BACKGROUND AND AIMS: The study aimed at comparing the performance of the novel
      optical AirtraqTM laryngoscope with the McCoyTM and conventional Macintosh
      laryngoscopes for ease of endotracheal intubation in patients with neck
      immobilisation using manual inline axial cervical spine stabilisation (MIAS)
      technique. METHODS: Ninety consenting American Society of Anaesthesiologist's
      physical status I-II patients, aged 18-60 years, scheduled for various surgeries
      requiring tracheal intubation were randomly assigned into three groups of thirty
      each to undergo intubation with Macintosh, AirtraqTM, or McCoyTM laryngoscope
      with neck immobilisation by MIAS technique. The ease of intubation based on
      Intubation difficulty scale (IDS) score, Cormack-Lehane grade of glottic view,
      optimisation manoeuvres and impact on haemodynamic parameters were recorded.
      Statistical analysis was performed with ANOVA and Bonferroni correction for post
      hoc tests. RESULTS: All patients in three groups had a comparable demographic
      profile and were successfully intubated. The AirtraqTM laryngoscope significantly
      reduced the IDS (mean - 0.43 +/- 0.81) as compared with both McCoyTM (mean - 1.63
      +/- 1.49, P = 0.001) and Macintosh laryngoscope (mean -2.23 +/- 1.92, P < 0.001)
      and improved the Cormack-Lehane glottic view (77% grade 1 view and no patients
      with grade 3 or 4 view). There were less haemodynamic variations during
      laryngoscopy with the AirtraqTM compared to the Macintosh laryngoscope, but there
      was not between the AirtraqTM and McCoyTM laryngoscope groups. CONCLUSION: In
      patients undergoing endotracheal intubation with cervical immobilisation,
      AirtraqTM laryngoscope was superior to the McCoyTM and Macintosh laryngoscopes,
      with greater ease of intubation and lower impact on haemodynamic variables.

PMID- 28515521
TI  - Comparative evaluation of AirtraqTM optical Laryngoscope and Miller's blade in
      paediatric patients undergoing elective surgery requiring tracheal intubation: A
      randomized, controlled trial.
AB  - BACKGROUND AND AIMS: The AirtraqTM optical laryngoscope is the only marketed
      videolaryngoscope for paediatric patients besides the fibre-optic bronchoscope.
      We hypothesized that intubation would be easier with AirtraqTM compared to Miller
      blade. Hence, we compared AirtraqTM with the Miller laryngoscope as intubation
      devices in paediatric patients. METHODS: This prospective, randomized study was
      conducted in a tertiary care teaching hospital. Sixty children belonging to
      American Society of Anesthesiologists' Grade I-II, aged 2-10 years, posted for
      routine surgery requiring tracheal intubation were randomly allocated to undergo
      intubation using a Miller (n = 30) or AirtraqTM (n = 30) laryngoscope. The
      primary outcome measure was time of intubation. We also measured ease of
      intubation, number of attempts, percentage of glottic opening score (POGO),
      haemodynamic changes and airway trauma. Student t test was used to analyse
      parametric data. RESULTS: Intubation time was comparable between Miller's
      laryngoscope (15.13 +/- 1.33s) compared to AirtraqTM (11.53 +/- 0.49 s) (P =
      0.29) The number of first and second attempts at intubation were 25 and 5 for the
      Miller laryngoscope and 29 and 1 for the AirtraqTM. Median visual analogue score
      (VAS) for ease of intubation was 5 in Miller group compared to 3 in AirtraqTM
      group. The median POGO score was 75 in the Miller group and 100 in the AirtraqTM
      group (P = 0.01). Haemodynamic changes were maximum and most significant
      immediately and 1 min after intubation. Airway trauma occurred in three patients
      (9.09%) in Miller group and one patient (3.33%) in AirtraqTM group. CONCLUSION:
      The AirtraqTM reduced the difficulty of tracheal intubation and degree of
      haemodynamic stimulation compared to the Miller laryngoscope in paediatric
      patients.

PMID- 28515523
TI  - Comparison of endotracheal intubation time in neutral position between C-Mac(r)
      and Airtraq(r) laryngoscopes: A prospective randomised study.
AB  - BACKGROUND AND AIMS: In the recent past, many novel devices such as AirTraq(r)
      and C-MAC(r) video laryngoscope (VL) have been introduced in an attempt to reduce
      anaesthetic morbidity and mortality associated with difficult intubation. In this
      study, we aimed to evaluate and compare C-MAC(r) VL with a standard Macintosh
      blade and the AirTraq(r) optical laryngoscope as a intubating devices with the
      patient's head in neutral position. METHODS: Sixty American Society of
      Anesthesiologist Physical Status I-II patients were randomly assigned to be
      intubated with C-MAC(r) VL (Group CM; n = 30) or AirTraq(r) (Group AT; n = 30) in
      the neutral position, with or without the application of optimization manoeuvres.
      The primary outcomes of this study were the success rate and the time taken to
      intubate. Glottic view, ease of tracheal intubation and haemodynamic responses
      were considered as secondary end points. RESULTS: The incidence of successful
      intubation was similar in both the groups (P = 1.00). However, the time for
      intubation was significantly less with C-MAC(r) VL (Group CM = 14.9 +/- 12.89 s,
      Group AT = 26.3 +/- 13.34 s; P = 0.0014). There was no significant difference
      between the two groups in terms of ease of intubation and glottic view. However,
      the haemodynamic perturbations were much less with C-MAC(r) VL. CONCLUSION: We
      conclude that both the devices were similar in visualising larynx in the neutral
      position with similar success rates of intubation. However, the C-MAC(r) VL was
      better with respect to intubation time and haemodynamic stability.

PMID- 28515524
TI  - Spinal anaesthesia for a caesarean section in a patient with paraneoplastic
      cerebellar ataxia.
AB  - Paraneoplastic cerebellar ataxia (PCA) is most frequently observed in
      gynaecological cancers, small cell lung cancer, breast cancer, Hodgkin's
      lymphoma, cancer testis or malignant thymoma. In the literature, there is no data
      related to the effects of PCA during pregnancy or reports on the effects of
      anaesthesia in patients with PCA. We present management of a pregnant woman with
      PCA who was suddenly unable to walk with PCA and for whom effective spinal
      anaesthesia was performed for an elective caesarean section with no
      complications.

PMID- 28515525
TI  - Management of an intraoperatively damaged endotracheal tube in a case of
      difficult airway using fibre-optic bronchoscope with minimal apnoea period.
AB  - Damage to the endotracheal tube (ETT) is common in head and neck surgeries,
      especially in maxillary osteotomy. Airway management in such a crisis is crucial
      as there is risk of aspiration of blood into lungs, hypoxia and apnoea. This case
      illustrates a patient with an anticipated difficult airway who had an
      intraoperative damage to the ETT and was successfully managed by re-intubation
      with fiberoptic bronchoscope in a minimal apnoea period of <15 s using a new
      technique.

PMID- 28515526
TI  - Fentanyl or ketamine pre-treatment to prevent withdrawal response to rocuronium.

PMID- 28515527
TI  - Can fluid resuscitation be a risk factor for laryngeal oedema in severe dengue?

PMID- 28515528
TI  - Perioperative management of a patient with haemophilia-A for major abdominal
      surgery.

PMID- 28515529
TI  - Failing to learn from the past: Report of a patient with twice failed central
      venous cannulation.

PMID- 28515531
TI  - Anaesthetic management of a pregnant woman with preeclampsia and Eisenmenger's
      syndrome: Role of advanced haemodynamic monitoring.

PMID- 28515530
TI  - Maternal patent ductus arteriosus with bidirectional shunt: Obstetric anaesthesia
      and its challenges.

PMID- 28515532
TI  - Asystole during rigid bronchoscopic stenting under general anaesthesia in a
      patient with tracheo-oesophageal fistula.

PMID- 28515533
TI  - Bilateral quadratus lumborum block for post-caesarean analgesia.

PMID- 28515534
TI  - Quadratus lumborum block for post-caesarean analgesia.

PMID- 28515536
TI  - Estimation of the linear mixed integrated Ornstein-Uhlenbeck model.
AB  - The linear mixed model with an added integrated Ornstein-Uhlenbeck (IOU) process
      (linear mixed IOU model) allows for serial correlation and estimation of the
      degree of derivative tracking. It is rarely used, partly due to the lack of
      available software. We implemented the linear mixed IOU model in Stata and using
      simulations we assessed the feasibility of fitting the model by restricted
      maximum likelihood when applied to balanced and unbalanced data. We compared
      different (1) optimization algorithms, (2) parameterizations of the IOU process,
      (3) data structures and (4) random-effects structures. Fitting the model was
      practical and feasible when applied to large and moderately sized balanced
      datasets (20,000 and 500 observations), and large unbalanced datasets with (non
      informative) dropout and intermittent missingness. Analysis of a real dataset
      showed that the linear mixed IOU model was a better fit to the data than the
      standard linear mixed model (i.e. independent within-subject errors with constant
      variance).

PMID- 28515537
TI  - Estimating spatially distributed turbulent heat fluxes from high-resolution
      thermal imagery acquired with a UAV system.
AB  - In this study, high-resolution thermal imagery acquired with a small unmanned
      aerial vehicle (UAV) is used to map evapotranspiration (ET) at a grassland site
      in Luxembourg. The land surface temperature (LST) information from the thermal
      imagery is the key input to a one-source and two-source energy balance model.
      While the one-source model treats the surface as a single uniform layer, the two
      source model partitions the surface temperature and fluxes into soil and
      vegetation components. It thus explicitly accounts for the different
      contributions of both components to surface temperature as well as turbulent flux
      exchange with the atmosphere. Contrary to the two-source model, the one-source
      model requires an empirical adjustment parameter in order to account for the
      effect of the two components. Turbulent heat flux estimates of both modelling
      approaches are compared to eddy covariance (EC) measurements using the high
      resolution input imagery UAVs provide. In this comparison, the effect of
      different methods for energy balance closure of the EC data on the agreement
      between modelled and measured fluxes is also analysed. Additionally, the
      sensitivity of the one-source model to the derivation of the empirical adjustment
      parameter is tested. Due to the very dry and hot conditions during the
      experiment, pronounced thermal patterns developed over the grassland site. These
      patterns result in spatially variable turbulent heat fluxes. The model comparison
      indicates that both models are able to derive ET estimates that compare well with
      EC measurements under these conditions. However, the two-source model, with a
      more complex treatment of the energy and surface temperature partitioning between
      the soil and vegetation, outperformed the simpler one-source model in estimating
      sensible and latent heat fluxes. This is consistent with findings from prior
      studies. For the one-source model, a time-variant expression of the adjustment
      parameter (to account for the difference between aerodynamic and radiometric
      temperature) that depends on the surface-to-air temperature gradient yielded the
      best agreement with EC measurements. This study showed that the applied UAV
      system equipped with a dual-camera set-up allows for the acquisition of thermal
      imagery with high spatial and temporal resolution that illustrates the small
      scale heterogeneity of thermal surface properties. The UAV-based thermal imagery
      therefore provides the means for analysing patterns of LST and other surface
      properties with a high level of detail that cannot be obtained by traditional
      remote sensing methods.

PMID- 28515538
TI  - Effects of Engaging in Repeated Mental Imagery of Future Positive Events on
      Behavioural Activation in Individuals with Major Depressive Disorder.
AB  - Depression is associated with decreased engagement in behavioural activities. A
      wide range of activities can be promoted by simulating them via mental imagery.
      Mental imagery of positive events could thus provide a route to increasing
      adaptive behaviour in depression. The current study tested whether repeated
      engagement in positive mental imagery led to increases in behavioural activation
      in participants with depression, using data from a randomized controlled trial
      (Blackwell et al. in Clin Psychol Sci 3(1):91-111, 2015.
      doi:10.1177/2167702614560746). Participants (N = 150) were randomized to a 4-week
      positive imagery intervention or an active non-imagery control condition,
      completed via the internet. Behavioural activation was assessed five times up to
      6 months follow-up using the Behavioural Activation for Depression Scale (BADS).
      While BADS scores increased over time in both groups, there was an initial
      greater increase in the imagery condition. Investigating mental imagery
      simulation of positive activities as a means to promote behavioural activation in
      depression could provide a fruitful line of enquiry for future research.

PMID- 28515539
TI  - Why Does Positive Mental Health Buffer Against Psychopathology? An Exploratory
      Study on Self-Compassion as a Resilience Mechanism and Adaptive Emotion
      Regulation Strategy.
AB  - Growing evidence suggests that positive mental health or wellbeing protects
      against psychopathology. How and why those who flourish derive these resilient
      outcomes is, however, unknown. This exploratory study investigated if self
      compassion, as it continuously provides a friendly, accepting and situational
      context for negative experiences, functions as a resilience mechanism and
      adaptive emotion regulation strategy that protects against psychopathology for
      those with high levels of positive mental health. Participants from the general
      population (n = 349) provided measures at one time-point on positive mental
      health (MHC-SF), self-compassion (SCS-SF), psychopathology (HADS) and negative
      affect (mDES). Self-compassion significantly mediated the negative relationship
      between positive mental health and psychopathology. Furthermore, higher levels of
      self-compassion attenuated the relationship between state negative affect and
      psychopathology. Findings suggest that especially individuals with high levels of
      positive mental health possess self-compassion skills that promote resilience
      against psychopathology. These might function as an adaptive emotion regulation
      strategy and protect against the activation of schema related to psychopathology
      following state negative affective experiences. Enhancing self-compassion is a
      promising positive intervention for clinical practice. It will not only impact
      psychopathology through reducing factors like rumination and self-criticism, but
      also improve positive mental health by enhancing factors such as kindness and
      positive emotions. This may reduce the future risk of psychopathology.

PMID- 28515540
TI  - Opportunities and Challenges for the Emerging Field of Positive Emotion
      Regulation: A Commentary on the Special Edition on Positive Emotions and
      Cognitions in Clinical Psychology.
AB  - The importance of developing a better understanding of positive emotion
      regulation in both healthy and clinical populations is now recognised. This
      special edition brings together leading figures in the positive emotion
      regulation field and has contributions characterizing positive phenomena,
      differentiating them from negative phenomena, and evaluating underlying
      psychological mechanisms that drive these phenomena. This commentary reviews
      these articles to highlight challenges and opportunities for this emerging field,
      including the need to better characterize positive phenomena, to be more explicit
      about how the links between negative and positive phenomena are conceptualised,
      to evaluate more robustly underlying mechanisms, to standardize measurement of
      positive constructs, and to ensure that these scientific findings lead to
      meaningful changes in real-world policy and practice.

PMID- 28515541
TI  - Automaticity of Attentional Bias to Threat in High and Low Worriers.
AB  - Individuals with high levels of worry are more likely than others to attend to
      possible threats, although the extent of top-down attentional control processes
      on this bias is unknown. We compared the performance of high (n = 26) and low
      worriers (n = 26) on a probe discrimination task designed to assess attention to
      threat cues, under cognitive load or no-load conditions. The expected difference
      between groups was confirmed, with high worriers being more likely to attend to
      threat cues than low worriers. Importantly however, there were no significant
      effects involving condition (cognitive load vs. no-load), nor any significant
      association with self-perceived attentional control ability. These results
      suggest that pathological worriers are more likely to attend to threat than are
      individuals with low levels of worry, regardless of task demands on limited
      cognitive control resources. This finding is consistent with the dominance of
      habitual bottom-up influences over top-down control processes in biased attention
      to threat.

PMID- 28515542
TI  - The Role of Cognitive Factors in Childhood Social Anxiety: Social Threat Thoughts
      and Social Skills Perception.
AB  - Models of cognitive processing in anxiety disorders state that socially anxious
      children display several distorted cognitive processes that maintain their
      anxiety. The present study investigated the role of social threat thoughts and
      social skills perception in relation to childhood trait and state social anxiety.
      In total, 141 children varying in their levels of social anxiety performed a
      short speech task in front of a camera and filled out self-reports about their
      trait social anxiety, state anxiety, social skills perception and social threat
      thoughts. Results showed that social threat thoughts mediated the relationship
      between trait social anxiety and state anxiety after the speech task, even when
      controlling for baseline state anxiety. Furthermore, we found that children with
      higher trait anxiety and more social threat thoughts had a lower perception of
      their social skills, but did not display a social skills deficit. These results
      provide evidence for the applicability of the cognitive social anxiety model to
      children.

PMID- 28515543
TI  - Empirical Reality of Dialectical Behavioral Therapy in Borderline Personality.

PMID- 28515544
TI  - The Importance of Cholesterol in Psychopathology: A Review of Recent
      Contributions.
AB  - AIM: The aim of this study was to describe systematically recent studies that
      show the importance of cholesterol in psychopathology. METHODS: This study was a
      review. The following databases were searched for relevant published articles on
      human studies: MEDLINE, Web of Science, EBSCOhost Academic Search Complete, and
      Psychology and Behavioral Sciences Collection (papers from January 2012 to March
      2016). RESULTS: Eighteen recent papers were selected, and thematic dimensions
      showing correlations between cholesterol and behavioral and psychopathological
      variables were depression, suicide, personality, and aggression. CONCLUSION: This
      paper demonstrates that recent research corroborates the idea that cholesterol
      plays an important role in governing behavior and psychopathology in humans.
      Deepening the studies in this field could be a promising avenue for future
      research, with implications for treating people with behavior or mental health
      problems.

PMID- 28515546
TI  - Use of Jonkman et al. Score for Visual Quantification of Electroencephalography
      as a Tool to Assess Disease Severity in Cortical Dementias.
AB  - OBJECTIVES: To study electroencephalography (EEG) changes in patients with
      cortical dementias (Alzheimer's disease [AD] and frontotemporal dementia (FTD).
      (1) To correlate EEG changes with clinical severity of dementia as assessed by
      rating scales. (2) To correlate global gray matter volume (GGMV) with EEG scores
      and clinical severity rating scales. PATIENTS AND METHODS: This is a prospective
      cross-sectional study involving patients fulfilling the criteria for Probable AD
      and FTD. A total of thirty patients (20 = FTD, 10 = AD) underwent detailed
      neuropsychological evaluation, dementia rating scales, EEG, and magnetic
      resonance imaging. Five EEG parameters were acquired and each parameter is scaled
      and the total score was compared with neuropsychological parameters and GGMV.
      RESULTS: For FTD, the mean age of patients was 58.85 +/- 6.87, mean mini-mental
      state examination score was 13.30 +/- 6.33, Hindi mental state examination: 14.35
      +/- 6.28, mean grant total EEG score (GTES): 7.80 +/- 5.39, and mean GGMV:
      464580.76 +/- 52127 mm3 and for AD, the same were 69.50 +/- 8.59, 12.90 +/- 5.56,
      14.20 +/- 5.31, 9.80 +/- 5.29, and 483208 +/- 47371.5 mm3, respectively. GTES for
      mild, moderate, and severe FTD are 2.33 +/- 1.528, 6.00 +/- 3.162, and 10.70 +/-
      5.677 and for AD it is 4, 7.50 +/- 4.041, 15 +/- 1.414, respectively. The GGMV
      for mild, moderate, and severe FTD was 511836 +/- 45005, 492693.1 +/- 50624, and
      430725 +/- 30744 and for AD it is 527217.3 +/- 36171, 503598 +/- 3006, and 440812
      +/- 33911. DISCUSSION: The most common EEG abnormalities in cortical dementias
      are reduced frequency of rhythmic background activity. There is a significant
      correlation between GTES and dementia severity and global gray matter volume but
      the proportional correlation with GTES and volumetric scores is not significant.
      CONCLUSION: EEG is a cheap and sensitive and easily available tool to assess
      disease severity in patients with cortical dementias and thus helps in planning
      the type of rehabilitatory interventions and prognostication.

PMID- 28515545
TI  - Traumatic Brain Injury and Neuropsychiatric Complications.
AB  - Traumatic brain injury (TBI) occurs when a blow or jolt to the head or a
      penetrating injury results in damage to the brain. It is the most frequent cause
      of hospitalization in young people with a higher prevalence in men. TBI is the
      leading cause of disability and mortality between the ages 1 and 45. TBI can be
      caused either by the direct result of trauma or due to a complication of the
      primary injury. The most common etiological factors for TBI are falls, road
      traffic accidents, violent physical assaults, and injuries associated with
      athletic activities. Following TBI, significant neurologic complications may
      occur which include seizures, dementia, Alzheimer's disease, and cranial nerve
      injuries. In addition, people may suffer from various psychiatric complications
      such as depression, posttraumatic stress disorder, generalized anxiety disorder,
      obsessive-compulsive disorder, and other cognitive and behavioral sequel that
      might significantly increase the comorbidity of the victims. Considering all of
      the above complications, TBI is one of the significant public health burdens.
      Literature has shown that only about 25% of people achieve long-term functional
      independence following TBI. In this paper, we focused not only on the
      epidemiology but also the etiology, complications following TBI and understanding
      their underlying pathogenesis. Further, we focused on analyzing the options to
      improve the treatment and rehabilitation following TBI in future.

PMID- 28515547
TI  - A Randomized Pilot Study of Brief Intervention versus Simple Advice for Women
      Tobacco Users in an Urban Community in India.
AB  - AIM: The study aimed to assess the efficacy of providing brief intervention (BI)
      for women tobacco users in a community-based setting. METHODS: In this open
      labeled randomized study, a representative sample of women (n = 100) from a
      community in East Delhi were screened using Alcohol, Smoking and Substance
      Involvement Screening Test. Eligible women were randomized to BI or simple advice
      (SA) arms. At baseline, they were assessed for tobacco use characteristics and
      severity of nicotine dependence using Fagerstrom's test for nicotine dependence.
      Intervention in the form of a single session of BI or SA to quit tobacco was
      provided at baseline. All participants were assessed at 1 week and 3 months
      following intervention. The principal outcome was self-reported abstinence from
      tobacco use at 3 months follow-up. RESULTS: The mean age of the sample was 43
      years (standard deviation = 13). Most women were married (80%), housewives (69%),
      illiterate (61%), socioeconomically disadvantaged and were smokeless tobacco
      users (94%). The subjects in the BI group were twice more likely to stop tobacco
      use as compared to individuals in the SA group (odds ratio = 2.2, 95% confidence
      interval: 0.962-5.197, P = 0.06). CONCLUSION: The study results are suggestive of
      beneficial effect of BI. A larger study might provide more significant results.

PMID- 28515548
TI  - Culturally Relevant Family Therapy Practice with Parents of Children and
      Adolescents.
AB  - BACKGROUND: India is diverse in culture, with multiple aspects that may not match
      with the Western societal picture. Hence, it has often been seen that therapists
      encounter unique aspects of therapy that is faced during actual practice, which
      is never written in any textbook or research papers. Substantial information is
      present through both outcome (efficacy and effectiveness) studies and process
      research, but it has very little impact of actual Marital and Family Therapy
      (MFT) practice. This paper throws light into "how" and "what" of family therapy
      with parents of children/adolescents having psychiatric disorders. MATERIALS AND
      METHODS: Focused group discussion was conducted with practicing family therapists
      and mental health professionals working in Psychiatric Tertiary Hospital
      (National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka,
      India). Qualitative analysis was done to disseminate process issues in therapy.
      RESULTS: Aspects that are vital for families having children and adolescent with
      psychiatric disorders include: Academic decline and loss of parental control as
      main reasons for seeking help, integration of models is noted to be beneficial,
      therapeutic alliance, intake sessions, conjoint sessions and individual sessions
      are important, cultural issues like gender of therapist, their cultural belief
      model, therapist's cultural competence need to be taken into consideration.
      CONCLUSIONS: Challenges and way-outs to overcome these has been mentioned and
      implications discussed.

PMID- 28515549
TI  - Evaluation of Modified Patient Health Questionnaire-9 Teen in South African
      Adolescents.
AB  - BACKGROUND: This report describes the findings of the survey conducted by South
      African Depression and Anxiety Group (SADAG) in a cohort of disadvantaged South
      African adolescent scholars in which PHQ-9 teen version was modified and adapted
      (PHQ-9M) to improve the response rate. METHOD: PHQ-9M was administered to 2025
      secondary students of 35 schools over 2 years in Gauteng Province, South Africa.
      RESULTS: The mean age was 15.8 years. 23% of respondents scored 9 or above, 26.7%
      reported suicidal ideations in last month, 21.8% reported lifetime suicide
      attempts and 9.3% had severe functional impairment. PHQ-9M showed a fair internal
      consistency and face validity in this study. CONCLUSION: The PHQ-9M could be
      useful in conducting surveys in settings of low mental health literacy after
      further evaluation of its psychometric properties. The high rates of suicidal
      ideations, suicide attempts, and functional impairment in this population suggest
      the need for preventive interventions.

PMID- 28515550
TI  - Communication Impairments in Children with Inborn Errors of Metabolism: A
      Preliminary Study.
AB  - PURPOSE: Inborn Errors of Metabolism (IEMs) are a group of complex genetic
      conditions, predominantly affecting the pediatric population. While the
      understanding and identification of various IEMs has significantly improved over
      recent times, not much is known about the communication disorders in this
      population. The present study focused on identification and profiling of
      communication impairments in children diagnosed with IEMs. METHODS: Data was
      obtained retrospectively from medical records of children visiting a tertiary
      care hospital over a period of ten years (2005 - 2014). Selected data was
      reviewed to obtain demographic details, clinical signs/manifestations, laboratory
      findings, risk factors, developmental disorders and reported communication
      impairments. RESULTS: The findings of the study showed a variety of clinical
      signs and laboratory findings in children with inborn errors of metabolism. A few
      of the risk factors observed in the group were consanguinity, sibling death and
      family history of other disorders. Many children with IEM displayed communication
      disorders, most common as the delay in speech and language development.
      CONCLUSIONS: The results of this study showed that various communication
      disorders were seen in almost half of the children with a diagnosis of IEM.
      Findings are discussed with implications for future research in this direction.

PMID- 28515551
TI  - Combining Metacognitive Strategies with Traditional Cognitive Behavior Therapy in
      Generalized Anxiety Disorder: A Case Illustration.
AB  - CONTEXT: Generalized anxiety disorder (GAD) is a challenging clinical condition
      to manage. Recent psychological models of GAD emphasis on the need to focus on
      metacognitive processes in addition to symptom reduction. AIMS: We examined the
      application of metacognitive strategies in addition to conventional cognitive
      behaviour therapy (CBT) techniques in an adult patient with GAD. SETTINGS AND
      DESIGNS: Asingle case design with pre- and post-assessments on clinician-rated
      scales was adopted. MATERIALS AND METHODS: Twelve weekly sessions of therapy were
      conducted on an outpatient basis. Assessments were carried out on clinical global
      impressions scales, Hamilton's anxiety rating scale at pre- and post-therapy
      points. STATISTICAL ANALYSIS: Pre- and post-therapy changes were examined using
      the method of clinical significance. RESULTS: A combination of traditional CBT
      with MCT was effective in addressing anxiety and worry in this patient with GAD.
      The case illustrates the feasibility of matching therapeutic strategies to
      patient's symptom list and demonstrates a blend of metacognitive strategies and
      conventional CBT strategies. CONCLUSIONS: In clinical practice, matching
      strategies to patient's problem list is important to be an effective approach.

PMID- 28515553
TI  - Long Loop Reflex 2 in Patients with Cortical Dementias: A Pilot Study.
AB  - INTRODUCTION: Dementia is a major public health problem and it appears to be a
      global epidemic. The prevalence is doubling every 5 years and it is expected that
      70% of persons above 60 years will live in developing countries by 2020 and 15%
      of them are likely to suffer from dementia. Disease modifying treatments work
      only if initiated very early; however, diagnostic tools are not always able to
      clearly differentiate the different types in very early stage. Therefore,
      inexpensive and easily available biomarkers are needed to know if collectively
      they will improve the sensitivity of specific diagnosis. Therefore, in this pilot
      study, we have tried to analyze if long loop reflex (LLR2) is differentially
      affected in these two conditions early in the course of Alzheimer's dementia (AD)
      and frontotemporal dementia (FTD) based on hypothesis taking into account the
      anatomical substrates involved. PATIENTS AND METHODS: Mild cases of clinically
      probable AD and FTD after appropriate inclusion criteria were subjected for LLR
      testing in the upper limb at median nerve. The presence or absence of LLR was
      assessed and also the latency, amplitude, and duration assessed. RESULTS AND
      CONCLUSION: LLR 2 is differentially affected in both these conditions. Absence of
      LLR2 was consistently seen in FTD which can be explained by early break down of
      frontal subcortical circuits in this condition as against AD. This is likely to
      serve as a very cheap and very early biomarker to differentiate the two common
      types of cortical dementias.

PMID- 28515552
TI  - The Influence of Psychosocial Dysfunctions in Chronic Schizophrenia Patients in
      Remission: A Hospital-Based Study.
AB  - BACKGROUND: Psychosocial dysfunctions in the various psychosocial areas in
      chronic schizophrenic patients predict the long-term course, outcome, and quality
      of life of these patients, which always varies with years of treatment.
      OBJECTIVE: To know the influence and compare the level of psychosocial
      dysfunctions and severity of disability burden in chronic schizophrenic patients
      who are in remission with duration of 5 and 20 years. MATERIALS AND METHODS: The
      sample was collected from the OPD of Mental Health Institute (COE), S.C.B.
      Medical College, Cuttack, Odisha, India. This study is a cross-sectional study. A
      total of 120 remitted schizophrenic patients (60 patients of each group with
      duration of 5 and 20 years), who fulfilled Nancy Andreasen criteria for Remission
      were selected for the study. Regional language of dysfunction analysis
      questionnaire (DAQ) was used to assess the level of psychosocial dysfunctions in
      personal, familial, social, vocational, and cognitive areas of each patient.
      RESULTS: Qualitative data were analyzed using Chi-square and quantitative data
      were analyzed using t-test and correlation as a test of significance.
      Statistically significant differences (P < 0.05) were found in all five domains
      of DAQ between two groups. Statistically significant difference (P < 0.05) was
      found between the two groups with respect to severity of the disability.
      CONCLUSION: This study confirms that there are definite and substantial
      psychosocial dysfunctions in personal, familial, social, vocational, and
      cognitive spheres with the advancement of the duration of illness in chronic
      schizophrenic patients.

PMID- 28515554
TI  - Personality Profile and Short-term Treatment Outcome in Patients with Alcohol
      Dependence: A Study from South India.
AB  - BACKGROUND: Studying personality profiles allows researchers to generate
      important hypotheses in risk factors and correlates of alcohol use/misuse.
      Studies examining the association between personality traits and treatment
      outcome are limited in India. We studied the correlation between personality and
      treatment outcome in patients with alcohol dependence. METHODS: Adult
      participants with alcohol dependence were recruited from the inpatient and
      outpatient wards of de-addiction unit of a tertiary care facility in India using
      a prospective design and followed up after 3 months. Questionnaires administered
      were revised NEO personality inventory (NEO-PI-R), alcohol use disorders
      identification test, and advanced warning of alcohol relapse (AWARE). RESULTS:
      Out of 99 recruited participants (92% males) with mean age of 37 (+/-8.36) years,
      82 (82.8%) patients were followed up to 3 months. E4 (activity) facet of the
      extraversion domain in the NEO-PI-R significantly correlated with the baseline
      drinking scores (r = 0.204, P = 0.042, n = 99) and AWARE scores (r = 0.276, P =
      0.043, n = 54). There was a significant negative correlation between the E2
      (gregariousness) facet and satisfaction with life scores (r = -0.211, P = 0.036,
      n = 99). Age at first drink was significantly lower among relapsers (P = 0.021).
      CONCLUSION: Our study suggests that factors related to extraversion,
      specifically, high activity might be associated with higher drinking as well as
      higher risk of alcohol relapse. Predicting alcohol relapse by studying the
      personality traits would help clinicians in improving treatment outcomes.

PMID- 28515556
TI  - Subacute Noninfective Inflammatory Encephalopathy: Our Experience and Diagnostic
      Problems.
AB  - INTRODUCTION: Immune dysregulation associated encephalopathies present with
      significant psychiatric manifestations and only a few soft neurological and
      general systemic features. They are generally resistant to treatment with
      psychiatric medications. Generalized orthostatic myoclonus and faciobrachial
      dystonic seizures are mistaken as Creutzfeldt-Jakob disease and subacute
      sclerosing panencephalitis. PATIENTS AND METHODS: Forty-two patients seen during
      2010-2015 and diagnosed as noninfective encephalopathy were analyzed. Those
      patients with infective causes and those who had significant features of systemic
      manifestations of vasculitis and other disorders of central nervous system were
      excluded from the study. They were investigated with cerebrospinal fluid imaging,
      electroencephalogram (EEG), and antibody profile. RESULTS: More than 70% patients
      had psychiatric manifestation as presenting features and reported to
      psychiatrist. Three patients had paraneoplastic and others N-methyl-D-aspartate,
      voltage-gated potassium channel, thyroid peroxidase, antinuclear antibody
      related, and few were due to unknown antibody. CONCLUSION: Serious diagnostic
      errors are common and early diagnosis is based on high degree suspicion in
      patients presenting with new-onset refractory psychosis. Soft neurological
      features should be looked for and EEG serves as a very sensitive tool in
      establishing organicity.

PMID- 28515555
TI  - Quantitative Balance and Gait Measurement in Patients with Frontotemporal
      Dementia and Alzheimer Diseases: A Pilot Study.
AB  - INTRODUCTION: Alzhiemers disease and Frontotemporal dementia are common
      neurodegenerative dementias with a wide prevalence. Falls are a common cause of
      morbidity in these patients. Identifying subclinical involvement of these
      parameters might serve as a tool in differential analysis of these distinct
      parameters involved in these conditions and also help in planning preventive
      strategies to prevent falls. PATIENTS AND METHODS: Eight patients in age and
      gender matched patients in each group were compared with normal controls.
      Standardizes methods of gait and balance aseesment were done in all persons.
      RESULTS: Results revealed subclinical involvement of gait and balancesin all
      groups specially during divided attention. The parameters were significantly more
      affected in patients. Patients with AD and FTD had involement of over all
      ambulation index balance more affected in AD patients FTD patients showed step
      cycle, stride length abnormalities. DISCUSSION: There is balance and gait
      involvement in normal ageing as well as patients with AD and FTD. The pattern of
      involvement in AD correlates with WHERE pathway involvement and FTD with frontal
      subcortical circuits involvement. CONCLUSION: Identification the differential
      patterns of involvement in subclinical stage might help to differentiate normal
      ageing and the different types of cortical dementias. This could serve as an
      additional biomarker and also assist in initiating appropriate training methods
      to prevent future falls.

PMID- 28515557
TI  - Dandy-Walker Variant with Schizophrenia: Comorbidity or Cerebellar Cognitive
      Affective Syndrome?
AB  - Dandy-Walker complex (DWC) is a series of neurodevelopmental anomalies involving
      the posterior cranial fossa. The cerebellum has long been considered to be
      involved in motor coordination and balance. However, it has now been noted to
      play an important role in higher order cognitive, emotional, and behavioral
      functions. The concept of cerebellar cognitive affective syndrome, describing a
      coherent spectrum of cognitive and behavioral disturbances in adults following
      cerebellar damage has long been proposed. There have been reported cases of co
      occurring psychiatric symptoms and DWC in literature, but the conclusive evidence
      for an association between the same remains lacking. Herein, we report a case of
      schizophrenia presenting along with Dandy-Walker Variant.

PMID- 28515558
TI  - A Rare Case of Complicated Opioid Withdrawal in Delirium Without Convulsions.
AB  - Opioids are one of the commonly abused substances in India. Opioid withdrawal
      symptoms classically include severe muscle cramps, bone aches, autonomic
      symptoms, anxiety, restlessness, insomnia, and temperature dysregulation.
      However, reports of cases with delirium during withdrawal are few. A 25-year-old
      male with severe opioid withdrawal symptoms developed delirium. Investigations
      were normal. There were no comorbidities, no significant past history and family
      history. Patient treated for opioid dependence with tapering doses of lorazepam
      and clonidine. He was discharged with naltrexone. Patient lapsed 3 months later
      with similar presentation. Complications such as convulsions and delirium are
      recognized in alcohol withdrawal. However, these are rare as a feature of opioid
      withdrawal. This case illustrates the need for psychiatrists and physicians to be
      aware of the possibilities of delirium with opioid withdrawal and monitoring for
      the same is important because of its complications.

PMID- 28515559
TI  - Arachnoid Cyst and Psychosis: The Troublemaker or Innocent Bystander.
AB  - Organic underpinning of a psychotic disturbance is often missed. Arachnoid cysts
      are considered a rare neurological tumor, few of which exhibit any
      symptomatology. In most cases, they are diagnosed by accident. Literature
      regarding the coexistence of arachnoid cysts with psychiatric disorders is
      sparse. Here, we present a case who presented with a typical presentation of
      psychosis which was not enough for suspecting for an organic etiology.

PMID- 28515560
TI  - Pseudocyst Pancreas with Delirium in a Married Alcohol Dependent Male: A Rare
      Presentation.
AB  - We herein present a patient with a history of heavy alcohol abuse who developed
      pseudocyst Pancreas and delirium, who came to our hospital for treatment. The
      patient recovered well with treatment.

PMID- 28515561
TI  - Efficacy of Myofascial Unwinding and Myofascial Release Technique in a Patient
      with Somatic Symptoms - A Case Report.
AB  - Depression is an aversion to activity disorder which could lead to somatic
      dysfunctions such as insomnia, excessive sleeping, body aches, listlessness, and
      irritable bowel syndrome. The World Health Organization has projected the
      depression to be the second leading cause of disability worldwide by 2020. The
      physical and mental ill effects of somatic depression can be addressed using the
      osteopathic manipulative treatment. Therefore, the purpose of the present case
      report is to explore the effect of myofascial release (MFR) technique and
      myofascial unwinding (MFU) in the somatic depression. We reported a case of a 39
      year-old female diagnosed as dysthymia with moderate depression with somatic
      symptoms. She was treated with MFR and MFU for 4 weeks. Depression was scored
      using Hamilton Depression Rating Scale (HDRS), and quality of life was measured
      using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q
      LES-Q-SF). Both were administered preintervention and 6 weeks postintervention.
      The application of MFR and MFU resulted in the improved scores on both HDRS and Q
      LES-Q-SF. The present case positive results have proven the effectiveness of MFR
      and MFU as an important adjunctive treatment strategy.

PMID- 28515562
TI  - Leukodystrophy Presenting as Hyperactivity and Bipolarity with Uncommon Adverse
      Drug Reaction.
AB  - Leukodystrophy is a group of demyelinating neurodegenerative diseases of brain
      with varied presentation and multiple etiologies. Prognosis is predominantly
      dismal. Misdiagnosis and wrong treatment are common in this group of rare
      neurological disorders, especially when it presents with psychiatric symptoms. In
      this case, importance of neurological and radiological evaluation and need for
      high diagnostic suspicion in treatment-resistant psychiatric disorders is
      highlighted.

PMID- 28515563
TI  - Secondary Eating Disorder: A Reality? Case Report of Post Brain Injury Sequelae.
AB  - Traumatic brain injury (TBI) can lead to changes in eating behavior patterns.
      This report describes the case of a patient with alcohol dependence presenting
      with behavioral changes and eating disorder following frontal lobe trauma. A 42
      year-old male, premorbidly well-adjusted presented with alcohol use in dependent
      pattern for years. He sustained a subdural hematoma in the frontal lobe following
      a road traffic accident 10 years back. Post-TBI, the patient, started having low
      frustration tolerance, aggressive outbursts, disinhibition, difficulty in
      persisting with tasks, apathy, amotivation, and craving for food with inability
      to control intake on the sight of food. On testing, a deficit in frontal lobe
      functions was seen. Magnetic resonance imaging scan showed large areas of gliosis
      and encephalomalacia involving both frontal lobes with parenchymal loss. Eating
      disorders have been reported after TBI. This case report underscores a major role
      of frontal-subcortical circuits in regulation of eating habits.

PMID- 28515565
TI  - Cushing's Syndrome and Treatment-Resistant Depression.

PMID- 28515564
TI  - Delayed Stevens-Johnson Syndrome Secondary to the Use of Lamotrigine in Bipolar
      Mood Disorder.
AB  - Lamotrigine is a mood-stabilizing drug used in maintenance treatment of bipolar I
      disease. There are adverse effects with lamotrigine such as a headache, blurred
      vision, diplopia, somnolence, ataxia, dizziness, rash, Stevens-Johnson syndrome
      (SJS), and toxic epidermal necrolysis. SJS is a life-threatening, blistering
      mucocutaneous disease. SJS is characterized by the presence of flat, diffuse
      erythematous maculopapular rashes with the involvement of <10% of the body
      surface area. Standard trigger is drugs including anticonvulsants, antibiotics,
      and Mycoplasma pneumoniae infection. We report a case where a patient developed
      SJS secondary to delayed-type hypersensitivity reaction after 6 months of the use
      of lamotrigine, while his initial response during the first 6 months did not show
      any sign of SJS.

PMID- 28515566
TI  - Autonomous Sensory Meridian Response: What is It? and Why Should We Care?

PMID- 28515567
TI  - Asymmetric, Tender Gynecomastia Induced by Olanzapine in a Young Male.

PMID- 28515568
TI  - Gender Differences in Persistent Delusional Disorder.

PMID- 28515569
TI  - Salami Slicing of Data Set, Translational Plagiarism, and Self-plagiarism: The
      Storyline.

PMID- 28515570
TI  - Association between hemodynamic modifications and clinical outcome of
      intracranial aneurysms treated using flow diverters.
AB  - Treatment of intracranial aneurysms (IAs) has been revolutionized by the advent
      of endovascular Flow Diverters (FDs), which disrupt blood flow within the
      aneurysm to induce pro-thrombotic conditions, and serves as a scaffold for
      endothelial ingrowth and arterial remodeling. Despite good clinical success of
      FDs, complications like incomplete occlusion and post-treatment rupture leading
      to subarachnoid hemorrhage have been reported. In silico computational fluid
      dynamic analysis of the pre- and post-treated geometries of IA patients can shed
      light on the contrasting blood hemodynamics associated with different clinical
      outcomes. In this study, we analyzed hemodynamic modifications in 15 IA patients
      treated using a single FD; 10 IAs were completely occluded (successful) and 5
      were partially occluded (unsuccessful) at 12-month follow-up. An in-house virtual
      stenting workflow was used to recapitulate the clinical intervention on these
      cases, followed by CFD to obtain pre- and post-treatment hemodynamics. Bulk
      hemodynamic parameters showed comparable reductions in both groups with average
      inflow rate and aneurysmal velocity reduction of 40.3% and 52.4% in successful
      cases, and 34.4% and 49.2% in unsuccessful cases. There was a substantial
      reduction in localized parameter like vortex coreline length and Energy Loss for
      successful cases, 38.2% and 42.9% compared to 10.1% and 10.5% for unsuccessful
      cases. This suggest that for successfully treated IAs, the localized complex
      blood flow is disrupted more prominently by the FD as compared to unsuccessful
      cases. These localized hemodynamic parameters can be potentially used in
      prediction of treatment outcome, thus aiding the clinicians in a priori
      assessment of different treatment strategies.

PMID- 28515571
TI  - Estimating yield gaps at the cropping system level.
AB  - Yield gap analyses of individual crops have been used to estimate opportunities
      for increasing crop production at local to global scales, thus providing
      information crucial to food security. However, increases in crop production can
      also be achieved by improving cropping system yield through modification of
      spatial and temporal arrangement of individual crops. In this paper we define the
      cropping system yield potential as the output from the combination of crops that
      gives the highest energy yield per unit of land and time, and the cropping system
      yield gap as the difference between actual energy yield of an existing cropping
      system and the cropping system yield potential. Then, we provide a framework to
      identify alternative cropping systems which can be evaluated against the current
      ones. A proof-of-concept is provided with irrigated rice-maize systems at four
      locations in Bangladesh that represent a range of climatic conditions in that
      country. The proposed framework identified (i) realistic alternative cropping
      systems at each location, and (ii) two locations where expected improvements in
      crop production from changes in cropping intensity (number of crops per year)
      were 43% to 64% higher than from improving the management of individual crops
      within the current cropping systems. The proposed framework provides a tool to
      help assess food production capacity of new systems (e.g. with increased cropping
      intensity) arising from climate change, and assess resource requirements (water
      and N) and associated environmental footprint per unit of land and production of
      these new systems. By expanding yield gap analysis from individual crops to the
      cropping system level and applying it to new systems, this framework could also
      be helpful to bridge the gap between yield gap analysis and cropping/farming
      system design.

PMID- 28515572
TI  - A family of Fe-N-C oxygen reduction electrocatalysts for microbial fuel cell
      (MFC) application: Relationships between surface chemistry and performances.
AB  - Different iron-based cathode catalysts have been studied for oxygen reduction
      reaction (ORR) in neutral media and then applied into microbial fuel cells (MFC).
      The catalysts have been synthesized using sacrificial support method (SSM) using
      eight different organic precursors named Niclosamide, Ricobendazole, Guanosine,
      Succinylsulfathiazole, Sulfacetamide, Quinine, Sulfadiazine and Pyrazinamide.
      Linear Sweep Voltammetry (LSV) curves were obtained for the catalysts using a O2
      saturated in 0.1 M potassium phosphate buffer and 0.1 M KCl solution and a
      Rotating Ring Disk Electrode (RRDE) setup in order to study the ORR
      characteristics. Additionally, we analyze the peroxide yield obtained for each
      catalyst which helps us determine the reaction kinetics. Those catalysts have
      been mixed with activated carbon (AC), carbon black (CB) and PTFE and pressed on
      a metallic mesh forming a pellet-like gas diffusion electrode (GDE). Results
      showed that Fe-Ricobendazole, Fe-Niclosamide and Fe-Pyrazinamide had the highest
      cathode polarization curves and highest power densities output that was above 200
      MUWcm-2. Fe-Ricobendazole, Fe-Niclosamide, Fe-Pyrazinamide, Fe-Guanosine Fe
      Succinylsulfathiazole and Fe-Sulfacetamide outperformed compared to Pt cathode.
      Fe-Sulfadiazene and Fe-Quinine performed better than AC used as control but less
      than Pt. Correlation of surface composition with performance showed that power
      density achieved is directly related to the total amount of nitrogen, and in
      particularly, N coordinated to metal and pyridinic and pyrrolic types while
      larger amounts of graphitic nitrogen result in worse performance.

PMID- 28515573
TI  - Problematisations of Complexity: On the Notion and Production of Diverse
      Complexities in Healthcare Interventions and Evaluations.
AB  - Within the literature on the evaluation of health (policy) interventions,
      complexity is a much-debated issue. In particular, many claim that so-called
      'complex interventions' pose different challenges to evaluation studies than
      apparently 'simple interventions' do. Distinct ways of doing evaluation entail
      particular ontologies and epistemologies of complexity. They differ in terms of
      whether they define complexity as a quantitative trait of interventions, whether
      they see evaluation as part of or outside the intervention, and whether
      complexity can be regarded as an emergent property of the intervention and its
      evaluation. In practice, evaluators and commissioners of large health care
      improvement programmes rely on different, sometimes contradictory, repertoires
      about what it means to conduct a 'good' evaluation. This is an ongoing matter
      negotiated between and among commissioners, researchers, and-sometimes-programme
      managers. In particular, notions of evaluability, usefulness and
      distance/independence are problematised in different ways and with diverse
      consequences, which, in turn, produce other notions and layers of complexity such
      as temporal, institutional and affective complexities. When (social science)
      researchers claim that one method or another is better able to grasp complexity,
      they elide the issue that any methodological choice emphasises some complexities
      and lets others fade into the background. Analysing the practicalities and
      emotions involved in evaluation studies opens up the notion of complexity to
      analytical scrutiny, and suggests a basis for co-theorising between biomedical,
      public health and social scientists (including Science and Technology Studies
      scholars).

PMID- 28515574
TI  - Autistic Heterogeneity: Linking Uncertainties and Indeterminacies.
AB  - Autism is a highly uncertain entity and little is said about it with any degree
      of certainty. Scientists must, and do, work through these uncertainties in the
      course of their work. Scientists explain uncertainty in autism research through
      discussion of epistemological uncertainties which suggest that diverse methods
      and techniques make results hard to reconcile, ontological uncertainties which
      suggest doubt over taxonomic coherence, but also through reference to autism's
      indeterminacy which suggests that the condition is inherently heterogeneous.
      Indeed, indeterminacy takes two forms-an inter-personal form which suggests that
      there are fundamental differences between individuals with autism and an intra
      personal form which suggests that no one factor is able to explain all features
      of autism within a given individual. What is apparent in the case of autism is
      that scientists put uncertainty and indeterminacy into discussion with one
      another and, rather than a well-policed epistemic-ontic boundary, there is a
      movement between, and an entwinement of, the two. Understanding scientists'
      dialogue concerning uncertainty and indeterminacy is of importance for
      understanding autism and autistic heterogeneity but also for understanding
      uncertainty and 'uncertainty work' within science more generally.

PMID- 28515576
TI  - Quality program in radiology: Persue or perish.

PMID- 28515575
TI  - Controls of primary production in two phytoplankton blooms in the Antarctic
      Circumpolar Current.
AB  - The Antarctic Circumpolar Current has a high potential for primary production and
      carbon sequestration through the biological pump. In the current study, two large
      scale blooms observed in 2012 during a cruise with R.V. Polarstern were
      investigated with respect to phytoplankton standing stocks, primary productivity
      and nutrient budgets. While net primary productivity was similar in both blooms,
      chlorophyll a -specific photosynthesis was more efficient in the bloom closer to
      the island of South Georgia (39  degrees W, 50  degrees S) compared to the open
      ocean bloom further east (12  degrees W, 51  degrees S). We did not find evidence
      for light being the driver of bloom dynamics as chlorophyll standing stocks up to
      165 mg m-2 developed despite mixed layers as deep as 90 m. Since the two bloom
      regions differ in their distance to shelf areas, potential sources of iron vary.
      Nutrient (nitrate, phosphate, silicate) deficits were similar in both areas
      despite different bloom ages, but their ratios indicated more pronounced iron
      limitation at 12  degrees W compared to 39  degrees W. While primarily the supply
      of iron and not the availability of light seemed to control onset and duration of
      the blooms, higher grazing pressure could have exerted a stronger control toward
      the declining phase of the blooms.

PMID- 28515577
TI  - Presidential address.

PMID- 28515578
TI  - Imaging in ductal plate malformations.
AB  - Ductal plate malformations are a heterogenous group of congenital fibrocystic
      liver diseases resulting from insult to the ductal plate at various stages of
      embryogenesis. As a result various biliary malformations, cysts, hamartomas and
      congenital hepatic fibrosis may be seen. We present a radiological pictorial of
      ductal plate malformations, accurate diagnosis of which is important for clinical
      management.

PMID- 28515579
TI  - Multimodality imaging of adult gastric emergencies: A pictorial review.
AB  - Acute gastric emergencies require urgent surgical or nonsurgical intervention
      because they are associated with high morbidity and mortality. Imaging plays an
      important role in diagnosis since the clinical symptoms are often nonspecific and
      radiologist may be the first one to suggest a diagnosis as the imaging findings
      are often characteristic. The purpose of this article is to provide a
      comprehensive review of multimodality imaging (plain radiograph, fluoroscopy, and
      computed tomography) of various life threatening gastric emergencies.

PMID- 28515580
TI  - Infectious pneumonia in the immunocompetent host: What the radiologist should
      know.
AB  - Lung infections are an important cause of morbidity and mortality, particularly
      because of the rising antimicrobial resistance. According to the clinical
      setting, they can be categorized as community-acquired pneumonia and hospital
      acquired pneumonia. Radiological patterns of lung infections are lobar
      consolidation, bronchopneumonia, interstitial pattern, and nodular pattern. In
      addition, typical imaging features of several infections serve as "red flag
      signs" in reaching a diagnosis or altering the management. It would be prudent
      for the radiologist to be well informed regarding these aspects of lung
      infections to be able to make a valuable contribution to the management.

PMID- 28515581
TI  - Castleman's disease: A rare indication for endovascular therapy for hemoptysis.
AB  - Castleman's disease (CD) is a rare lympho-proliferative disorder due to faulty
      immune regulation resulting in proliferation of lymphatic tissue. The vascular
      supply to these lesions have been reported to arise from the bronchial, internal
      mammary and the intercostal arteries. We report a case of hemoptysis secondary to
      intrathoracic CD with vascular supply arising from the left inferior phrenic
      artery which was successfully embolised with polyvinyl alcohol (PVA) particles.

PMID- 28515582
TI  - Evaluation of MR perfusion abnormalities in organophosphorus poisoning and its
      correlation with SPECT.
AB  - AIM: Acute organophosphate (OP) pesticide poisoning causes substantial morbidity
      and mortality worldwide. Many imaging modalities, such as computerized tomography
      (CT), magnetic resonance imaging (MRI), and single photon emission computed
      tomography (SPECT) of the brain, have been used for quantitative assessment of
      the acute brain insult caused by acute OP poisoning. Perfusion defects on SPECT
      in acutely poisoned patients with OPs have been described, however, MR perfusion
      abnormalities have not been described in the literature. MR perfusion Imaging has
      the advantage of having higher spatial resolution, no radiation, and better
      availability. MATERIALS AND METHODS: In this prospective study, 20 patients who
      ingested OP compounds were included. All the patients underwent brain SPECT on a
      dual head SPECT gamma camera and MRI brain on a 1.5T MR system. Neurocognitive
      tests were performed for all patients. RESULTS: SPECT showed perfusion defects in
      7 patients and total number of perfusion defects were 29. On MR perfusion, based
      on the cut-off values of normalized cerebral blood volume (nCBV) ratios and
      normalized cerebral blood flow (nCBF) ratios, the total number of patients
      showing perfusion defects were 6 and 8; and the total number of perfusion defects
      were 29 and 45, respectively. There was significant difference of the nCBV ratios
      and nCBF ratios between the control group (n = 20) and positive patients group (n
      = 6 and n = 8, respectively) (P > 0.05). All the defects seen on SPECT were well
      appreciated on nCBF maps (MRI perfusion) suggestive of 100% correlation.
      CONCLUSION: MR perfusion imaging can be used as an effective modality for
      evaluation in acute OP poisoning.

PMID- 28515583
TI  - Cavernous sinus melanoma: A rare tumor.
AB  - Primay melanoma of the cavernous sinus is very rare with only few cases reported
      in the literature. We present the cross-sectional imaging findings of this rare
      tumor. The differential diagnosis for cavernous sinus mass lesion is wide as it
      contains vital neurovascular structures that may be affected by vascular,
      neoplastic, infective, and infiltrative lesions arising in the cavernous sinus
      proper or via extension from adjacent intra and/or extracranial regions.
      Radiologic imaging can narrow the differential diagnosis, however, imaging cannot
      definitely reach single diagnosis if they present in atypical form with hemorrage
      and cystic degeneration. This case report illustrates that primary cavernous
      sinus melanoma may present as a atypical tumor with diagnostic dilemma.

PMID- 28515584
TI  - Frontal sinus osteoma with pneumocephalus: A rare cause of progressive
      hemiparesis.
AB  - Osteomas of paranasal sinuses are common benign tumors and are diagnosed
      incidentally. However, osteomas complicated by pneumocephalus with air fluid
      level presenting with progressive hemiparesis is rare. Here, we present a case
      report of a 22-year-old male who presented with left-sided progressive
      hemiparesis with history of generalized headache since 2 years.

PMID- 28515585
TI  - Calcification of the submandibular gland in a patient with chickenpox.
AB  - The pneumonia virus of chickenpox is now known to cause scattered calcified foci
      in the lungs, however to our knowledge, recent literature has not discussed
      calcification in the salivary glands. A 15-year-old boy consulted the department
      of radiology because of a swelling on the right side of the submandibular area.
      Radiological assessment included an ultrasonography and computerized tomography
      scan of the neck area, which demonstrated intraparenchymal amorph calcification,
      with approximately 13 mm diameter in the right submandibular gland. General
      condition and oral intake was good without distress in the patient, and hence he
      was discharged on the seventh day of follow-up treatment.

PMID- 28515586
TI  - Utility of supplemental screening with breast ultrasound in asymptomatic women
      with dense breast tissue who are not at high risk for breast cancer.
AB  - OBJECTIVE: To assess the results of an initial round of supplemental screening
      with hand-held bilateral breast ultrasound following a negative screening
      mammogram in asymptomatic women with dense breast tissue who are not at high risk
      for breast cancer. MATERIALS AND METHODS: A retrospective, Health Insurance
      Portability and Accountability Act compliant, Institutional Research Board
      approved study was performed at a single academic tertiary breast center.
      Informed consent was waived. A systematic review of the breast imaging center
      database was conducted to identify and retrieve data for all asymptomatic women,
      who were found to have heterogeneously dense or extremely dense breast tissue on
      screening bilateral mammograms performed from July 1, 2010 through June 30, 2012
      and who received a mammographic final assessment American College of Radiology's
      (ACR) Breast Imaging Reporting and Data System (BI-RADS) category 1 or BI-RADS
      category 2. Hand-held screening ultrasound was performed initially by a
      technologist followed by a radiologist. Chi-square and t-test were used and
      statistical significance was considered at P < 0.05. RESULTS: A total of 1210
      women were identified. Of these, 394 underwent the offered supplemental screening
      ultrasound. BI-RADS category 1 or 2 was assigned to 323 women (81.9%). BI-RADS
      category 3 was assigned to 50 women (12.9%). A total of 26 biopsies/aspirations
      were recommended and performed in 26 women (6.6%). The most common finding for
      which biopsy was recommended was a solid mass (88.5%) with an average size of 0.9
      cm (0.5-1.7 cm). Most frequent pathology result was fibroadenoma (60.8%). No
      carcinoma was found. CONCLUSION: Our data support the reported occurrence of a
      relatively high number of false positives at supplemental screening with breast
      ultrasound following a negative screening mammogram in asymptomatic women with
      dense breast tissue, who are not at a high risk of developing breast cancer, and
      suggests that caution is necessary in establishing wide implementation of this
      type of supplemental screening for all women with dense breast tissue without
      considering other risk factors for breast cancer.

PMID- 28515587
TI  - Fetal intra abdominal umbilical vein varix: Case series and review of literature.
AB  - Fetal intraabdominal umbilical vein varix (FIUV) is focal dilatation of the
      intrabdominalumbilical vein of thefetus. It appears as a round or fusiform cystic
      structure in thefetal abdomen, which shows continuity with the umbilical vein
      ongrayscale andcolor Dopplerimaging. The diagnostic criteria include the FIUV
      varix diameter at least 50% wider than the diameter of the intrahepatic umbilical
      veinand an intraabdominal umbilical vein diameter exceeding 9 mm orgreater than
      twostandard deviations above the mean for gestational age. We report three cases,
      two cases with isolated FIUV and favorable outcome and the third case with FIUV
      and atrioventricular septal defect, where trisomy 21 (Down syndrome) was
      diagnosed.

PMID- 28515588
TI  - Placental mesenchymal dysplasia: What every radiologist needs to know.
AB  - Placental mesenchymal dysplasia (PMD) is an uncommon vascular anomaly of the
      placenta characterized by placentomegaly with multicystic placental lesion on
      ultrasonography and mesenchymal stem villous hyperplasia on histopathology.
      Placental mesenchymal dysplasia should be considered in the differential
      diagnosis of cases of multicystic placental lesion such as molar pregnancy,
      chorioangioma, subchorionic hematoma, and spontaneous abortion with hydropic
      placental changes. However, lack of high-velocity signals inside the lesion and a
      normal karyotype favor a diagnosis of PMD. PMD must be differentiated from
      gestational trophoblastic disease because management and outcomes differ. We
      report the case of an 18-year-old female at 15 weeks of gestation with
      sonographic findings suggestive of placental mesenchymal dysplasia. The diagnosis
      was confirmed on histopathology.

PMID- 28515589
TI  - Spectrum of pulmonary valve morphology and its relationship to pulmonary trunk in
      tetralogy of Fallot.
AB  - BACKGROUND: Tetralogy of Fallot (TOF) is a complex congenital heart disease with
      anatomic variations. Although the pulmonary valve in TOF is abnormal, it has not
      been studied well, especially on newer imaging modalities such as multidetector
      computed tomography (CT), which gives excellent anatomic detail. AIMS: The aim of
      this study was to assess the morphology of pulmonary valve in TOF on CT and
      evaluate its association with the degree of hypoplasia of infundibulum and
      pulmonary trunk. MATERIALS AND METHODS: The cardiac CT scans of 30 patients with
      TOF were reviewed to evaluate the morphology of the pulmonary valve,
      infundibulum, and pulmonary arteries. Fisher's exact test was performed to
      examine the association between pulmonary valve morphology and degree of
      hypoplasia of the infundibulum and pulmonary trunk. RESULTS: 16.7% of patients
      with TOF had pulmonary atresia. The prevalence of tricuspid, bicuspid, and absent
      valves were 10%, 53.3% and 6.7%, respectively. In another 13.3% of patients,
      although valve tissue was present, exact morphology could not be determined on
      CT. The commissures of 62.5% of the bicuspid valves were at 12 o'clock and 6
      o'clock or slightly off the midline. There was statistically significant
      association between valve morphology and degree of infundibular hypoplasia (P <
      0.001) and calibre of pulmonary trunk (P < 0.001). CONCLUSION: Morphological
      abnormality of the pulmonary valve is common in TOF. The most common type of
      pulmonary valve in TOF patients is bicuspid valve with commissures at 12 o'clock
      and 6 o'clock or slightly off the midline. Fewer cusps of the pulmonary valve are
      associated with a more severe degree of pulmonary artery hypoplasia.

PMID- 28515590
TI  - Prenatal diagnosis of a rare aortic arch anomaly with left aortic arch and right
      ductus arteriosus: Cross ribbon sign.
AB  - Here, we report a fetus with a rare aortic arch anomaly with left aortic arch and
      right ductus arteriosus, which has not been reported so far. In this condition,
      the aorta extends to the left of the trachea as in normal, while the ductus
      arteriosus extends to the right of the trachea and joins the descending aorta
      posterior to the trachea, with a cross-ribbon sign.

PMID- 28515591
TI  - The current status of pediatric radiology in India: A conference-based survey.
AB  - INTRODUCTION: Like most other developing countries, India has a large proportion
      of children among its population. However, the facilities for adequate treatment
      of this large population is inadequate. The development of pediatric radiology as
      a subspecialty is still at an infant stage in India. The goal of our study was to
      assess the awareness about the current status of pediatric radiology in India.
      MATERIALS AND METHODS: A questionnaire was handed over to all attendees of a
      pediatric radiology conference to assess their opinion regarding the adequacy of
      pediatric training and practice in India. The questionnaire consisted of 10
      multiple-choice and two descriptive questions. Descriptive statistical methods
      were used for analyzing the results. RESULTS: Eighty-one out of 400 delegates
      responded to the questionnaire. Among these 81 respondents, 50 (61.7%) felt that
      exposure to pediatric cases during postgraduate course was inadequate. Sixty
      three out of 81 (77.7%) respondents thought that specialized training is required
      for practicing pediatric radiology, and 79 respondents (97%) felt that the number
      of such training programmes should increase. Forty-five out of 81 respondents
      (55.5%) were interested in pursuing pediatric radiology as a career. CONCLUSION:
      According to the opinion of the respondents of our survey, pediatric radiology
      remains an underdeveloped speciality in India. Considering the proportion of the
      population in the pediatric age and the poor health indicators in this age group,
      elaborate measures, as suggested, need to be implemented to improve pediatric
      radiology training and the care of sick children in India.

PMID- 28515592
TI  - Inguinoscrotal hernia in infants: Three case reports in ultrasound diagnosis.
AB  - An inguinal hernia occurs when an intestinal loop or part of the omentum or
      genital organs passes into the scrotal cavity or labia through an incompletely
      obliterated processus vaginalis. Inguinal hernias are most common in preterm
      neonates, especially at 32-weeks gestation. Content of hernia is mostly bowel and
      ovary/testicles. Presence of uterus in herniated sac is rare, and only few cases
      are reported in literature. Hernia is more frequently located on the right side
      because the right processus vaginalis closes later than the left. Physical
      examination is sufficient to enable diagnosis in most cases. Ultrasound
      examination is indicated in patients with inconclusive physical findings, in
      patients with acute scrotum, and to investigate contralateral involvement in
      patients in whom only a unilateral hernia is clinically evident. Routinely, color
      or power Doppler imaging is used in inguinal-scrotal hernia to investigate
      intestinal and testicular/ovarian perfusion. Urgent surgery is indicated in
      patients with an akinetic dilated bowel loop (a sign of strangulation) or
      impaired testicular/ovarian perfusion.

PMID- 28515593
TI  - Role of penumbra mechanical thrombectomy device in acute dural sinus thrombosis.
AB  - BACKGROUND: In dural venous sinus thrombosis (DVST), the mortality ranges 5-30%.
      Deep venous system involvement and septic dural sinus thrombosis have a higher
      mortality rate. In acute occlusion, collateral flow may not be established, which
      may result in significant edema and mass effect. Endovascular interventions may
      be considered as a treatment option in appropriate high-risk patients with DVST.
      MATERIALS AND METHODS: Eight patients with magnetic resonance imaging (MRI)
      confirmed dural sinus thrombosis, who did not respond to the conventional
      standard medical treatment, were subsequently treated with mechanical
      thrombectomy using the Penumbra System(r). In all cases, medical treatment
      including anticoagulants were continued following the procedure for a minimum
      period of 1 year. RESULTS: Recanalization of the dural sinus thrombosis was
      achieved in all 8 cases. There were no immediate or late endovascular-related
      complications. One death occurred due to an unrelated medical event. At 6 months,
      there was notable improvement in the modified Rankin Score (mRS), with 5/8 (62%)
      patients achieving mRS of 2 or less. The follow-up ranged between 3 months and 26
      months (mean: 14.5 months), and there were no new neurological events during the
      follow-up period. CONCLUSION: Cerebral venous sinus thrombosis is a rare but life
      threatening condition that demands timely diagnosis and therapy. In cases of
      rapidly declining neurological status despite standard therapy with systemic
      anticoagulation and anti-edema measures, mechanical thrombectomy could be a
      lifesaving and effective option. In this study, good outcomes were observed in
      the majority of patients at long-term follow up.

PMID- 28515594
TI  - Radiofrequency ablation of osteoid osteoma in common and technically challenging
      locations in pediatric population.
AB  - CONTEXT: Percutaneous radiofrequency ablation (RFA) of osteoid osteoma has a high
      technical and clinical success rate. However, there is limited data on its use in
      the pediatric population, especially in technically challenging locations.
      OBJECTIVE: To assess the safety and efficacy of computed tomography (CT)-guided
      percutaneous RFA of osteoid osteoma in pediatric population. PATIENTS AND
      METHODS: From June 2009 to May 2014, 30 patients with osteoid osteoma were
      treated with CT-guided RFA in common (25 cases) and technically challenging (five
      cases: four near articular surface and one in sacrum) locations. Therapy was
      performed under general anesthesia with a three-array expandable RF probe for 6
      min at 90 degrees C and power of 60-100 W. The patients were discharged next day
      under instruction. The treatment success was evaluated in terms of pain relief
      before and after (1 day, 1 month, and 6 months) treatment. RESULTS: Technical
      success was achieved in all patients (100%). Primary clinical success was 96.66%
      (29 of total 30 patients), despite the pediatric population and atypical
      location. One patient had persistent pain after 1 month and was treated
      successfully with a second procedure (secondary success rate was 100%). One
      patient had immediate complication of weakness of right hand and fingers
      extension. No delayed complications were observed. CONCLUSIONS: CT-guided RFA is
      relatively safe and highly effective for treatment of osteoid osteoma in
      pediatric population, even in technically difficult locations.

PMID- 28515595
TI  - Percutaneous transhepatic techniques for management of biliary anastomotic
      strictures in living donor liver transplant recipients.
AB  - AIM: To retrospectively analyze the percutaneous transhepatic techniques and
      their outcome in the management of biliary strictures in living donor liver
      transplant (LDLT) recipients. MATERIALS AND METHODS: We retrieved the hospital
      records of 400 LDLT recipients between 2007 and 2015 and identified 45 patients
      with biliary strictures. Among them, 17 patients (37.8%) (Male: female = 13:4;
      mean age, 36.1 +/- 17.5 years) treated by various percutaneous transhepatic
      biliary techniques alone or in combination with endoscopic retrograde
      cholangiopancreatography (ERCP) were included in the study. The technical and
      clinical success of the percutaneous management was analyzed. RESULTS:
      Anastomotic strictures associated with leak were found in 12/17 patients (70.6%).
      Ten out of 12 (83.3%) patients associated with leak had more than one duct-duct
      anastomoses (range, 2-3). The average duration of onset of stricture in patients
      with biliary leak was 3.97 +/- 2.68 months and in patients with only strictures
      it was 14.03 +/- 13.9 months. In 6 patients, endoscopic-guided plastic stents
      were placed using rendezvous technique, plastic stent was placed from a
      percutaneous approach in 1 patient, metallic stents were used in 2 patients,
      cholangioplasty was performed in 1 patient, N-butyl- 2-cyanoacrylate embolization
      was done in 1 child with biliary-pleural fistula, internal-external drain was
      placed in 1 patient, and only external drain was placed in 5 patients. Technical
      success was achieved in 12/17 (70.6%) and clinical success was achieved in 13/17
      (76.5%) of the patients. Posttreatment mean time of follow-up was 19.4 +/- 13.7
      months. Five patients (29.4%) died (two acute rejections, one metabolic acidosis,
      and two sepsis). CONCLUSIONS: Percutaneous biliary techniques are effective
      treatment options with good outcome in LDLT patients with biliary complications.

PMID- 28515596
TI  - Balloon occluded retrograde transvenous obliteration for bleeding gastric
      varices: Eyes see what the mind knows.
AB  - Approximately one in six patients with portal hypertension who develop varices at
      sites of portosystemic venous collaterals has gastric varices due to hepatofugal
      flow into the gastric veins. Bleeding from gastric varices, though less common,
      has a higher mortality and morbidity compared to bleeding esophageal varices,
      which are easier to manage endoscopically. The efferent channel for gastric
      varices is mostly the gastrorenal shunt (GRS) which opens into the left renal
      vein. Balloon-occluded transvenous obliteration (BRTO) involves accessing the GRS
      with an aim to temporarily occlude its outflow using a balloon catheter and at
      the same time injecting sclerosant mixture within the varix so as to cause its
      thrombosis and thereby obliteration. BRTO is one of the mainstays of minimally
      invasive treatment for bleeding gastric varices. In the minority of cases where
      the GRS is absent, conventional BRTO is technically not possible. However,
      accessing the small alternate shunt from the inferior phrenic vein may be
      possible if one is aware of its existence.

PMID- 28515598
TI  - Gorham's syndrome vs generalized lymphagiomatosis: A close call.

PMID- 28515597
TI  - Tibial periosteal ganglion cyst: The ganglion in disguise.
AB  - Soft tissue ganglions are commonly encountered cystic lesions around the wrist
      presumed to arise from myxomatous degeneration of periarticular connective
      tissue. Lesions with similar pathology in subchondral location close to joints,
      and often simulating a geode, is the less common entity called intraosseous
      ganglion. Rarer still is a lesion produced by mucoid degeneration and cyst
      formation of the periostium of long bones, rightly called the periosteal
      ganglion. They are mostly found in the lower extremities at the region of pes
      anserinus, typically limited to the periosteum and outer cortex without any
      intramedullary component. We report the case of a 62 year-old male who presented
      with a tender swelling on the mid shaft of the left tibia, which radiologically
      suggested a juxtacortical lesion extending to the soft tissue or a soft tissue
      neoplasm eroding the bony cortex of tibia. It was later diagnosed definitively as
      a periosteal ganglion in an atypical location, on further radiologic work-up and
      histopathological correlation.

PMID- 28515599
TI  - Author's reply.

PMID- 28515600
TI  - A novel presentation of tubular adenoma of the breast as an intraductal mass:
      Diagnostic considerations and pathologic correlation.

PMID- 28515601
TI  - Quality Indicators Compliance Survey in Indian Intensive Care Units.
AB  - CONTEXT: The quality of health care and outcomes of Intensive Care Unit (ICU)
      have been a major subject of discussion in the past decade. Quality indicators in
      ICUs maintain an order of uniformity and standard care of delivery across ICUs.
      AIMS: In this study, we tried to analyze the percentage compliance of quality
      indicators in ICU across our country. METHODS: Four hundred complete
      questionnaire forms were collected in two stages by means of conducting a survey
      and through email responses to the survey questionnaire. Data were tabulated and
      evaluated in percentage responses. RESULTS: Monitoring of infection control
      measures such as hand hygiene (77%), monitoring of ICU-acquired infections
      (>75%), and quality and policy measures (>70%) were promising. Improvements are
      required in following end-of-life pathways (52%) and staffing patterns in ICU.
      ICU discharge timings (41%), standardized mortality ratio monitoring (39%), and
      multidisciplinary rounds (58%) in ICUs are few areas we need to develop further.
      CONCLUSION: The future of critical care looks promising with growing number of
      trained intensivists and hospitals functioning with an average ICU bed strength
      of 30-40. Such surveys need to be performed regularly to improve the patient care
      and safety across ICUs.

PMID- 28515602
TI  - Respiratory Multiplex Polymerase Chain Reaction: An Important Diagnostic Tool in
      Immunocompromised Patients.
AB  - BACKGROUND: Viruses and atypical pathogens can cause significant respiratory
      illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR)
      has improved the diagnostic yield of pathogens, and it is easier to identify the
      co-infections also. The present study was done to evaluate the performance of
      MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients.
      METHODS: Atotal of 177 BAL specimens collected over a 19 months period from
      immunocompromised patients with respiratory illness were analyzed with the MPCR
      and aerobic culture. Patients were divided into four according to the pathogens.
      Category V (only viral), Category NV (nonviral, i.e., bacteria and atypical),
      Category M (mixed, i.e., both viral and nonviral pathogen), and Category UK
      (unknown etiology). RESULTS: MPCR identified the causative pathogen in 59.3% of
      patients while culture could identify only in 37.8% of patients. Most frequent
      etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus
      (21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category
      were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK
      (27.1%). Mortality was significantly higher in patients of Category M having
      mixed infections. CONCLUSION: MPCR is highly sensitive and rapid tool which can
      be considered in the routine diagnostic algorithm of respiratory illness in
      immunocompromised patients.

PMID- 28515604
TI  - Development and Psychometric Evaluation of the Pre-hospital Medical Emergencies
      Early Warning Scale.
AB  - INTRODUCTION: The number of requests for emergency medical services (EMSs) has
      increased during the past decade. However, most of the transports are not
      essential. Therefore, it seems crucial to develop an instrument to help EMS staff
      accurately identify patients who need pre-hospital care and transportation. The
      aim of this study was to develop and evaluate the psychometric properties of the
      Pre-hospital Medical Emergencies Early Warning Scale (Pre-MEWS). MATERIALS AND
      METHODS: This mixed-method study was conducted in two phases. In the first phase,
      a qualitative content analysis study was conducted to identify the predictors of
      medical patients' need for pre-hospital EMS and transportation. In the second
      phase, the face and the content validity as well as the internal consistency of
      the scale were evaluated. Finally, the items of the scale were scored and scoring
      system was presented. RESULTS: The final version of the scale contained 22 items
      and its total score ranged from 0 to 54. CONCLUSIONS: Pre-MEWS helps EMS staffs
      properly understand medical patients' conditions in pre-hospital environments and
      accurately identify their need for EMS and transportation.

PMID- 28515603
TI  - Correlation of Serum Vitamin D Level with Mortality in Patients with Sepsis.
AB  - BACKGROUND: Sepsis is the leading cause of mortality in the critically ill.
      Recently, it has been found in many studies that many trace elements and
      nutrients do have an effect on human body and if supplemented can improve the
      prognosis in patients with sepsis. AIM AND OBJECTIVES: Primary objective: Whether
      low Vitamin D is associated with mortality. Secondary objective: To find out
      association of low Vitamin D levels and morbidity in terms of length of hospital
      and Intensive Care Unit (ICU) stay. SUBJECTS AND METHODS: Following ethical
      approval, consent will be sought from either the patient or assent from a near
      relative. Successive patients admitted to the medical emergency and ICU at
      tertiary care health center who fulfill the following criteria for sepsis, within
      a 24 h time window, were included in the study. RESULTS: Among 88 patients
      evaluated in our study 15 patients (18.2%) were found to have adequate Vitamin D
      levels and seven patients (8%) were found insufficient and rest 52 patients
      (73.9%) were found deficient in Vitamin D. Age of the patients ranged between 18
      and 82 years with mean (+/-standard deviation) 45.02 +/- 17.69 years. Mean
      Vitamin D level was found significantly higher among patients with positive
      outcome than those with unfavorable outcome (expiry) (t = 2.075, P = 0.04). On
      comparison of the length of hospital stay (morbidity) with Vitamin D levels, we
      found statistically significant inverse relation between Vitamin D levels and
      length of hospital stay. CONCLUSION: Vitamin D deficiency leads to increased risk
      of mortality in the critically ill along with prolonged hospital stay.

PMID- 28515606
TI  - Gender-based Assessment of Survival in Trauma-hemorrhagic Shock: A Retrospective
      Analysis of Indian Population.
AB  - INTRODUCTION: Trauma-hemorrhagic shock (THS) is a leading cause of death. Female
      rats and women experience better outcomes in terms of survival after major trauma
      as compared to males. There are limited data in Indian population. Authors
      studied the gender-based outcome of patients with Class IV hemorrhagic shock due
      to blunt trauma and the distribution of factors among males and females which are
      known to affect outcome. MATERIALS AND METHODS: It was a retrospective study with
      data of trauma victims between January 2008 and July 2013. Road traffic crash
      (RTC), fall, or assault of all ages with Class IV hemorrhagic shock on arrival
      was included in the study, and data were collected on demographic, clinical, and
      laboratory parameters. Drowning, burns, penetrating injuries, and septic,
      neurogenic, and cardiogenic shock were excluded from the study. RESULTS: Seven
      hundred and eighty-one patients were analyzed under three groups: (i) overall
      group including all patients (n = 781), (ii) male group (n = 609), and (iii)
      female group (n = 172). After adjusting all variables, mortality was
      significantly lower in females as compared to males following THS (P < 0.05).
      Age, blood pressure, pulse, male gender, and fall and RTC as mode of injury (MOI)
      were independent predictors of mortality (P < 0.05) in overall group. Among
      males, age, pulse, and RTC as a MOI were significant (P < 0.05), while in
      females, only systolic blood pressure (SBP) was independent predictor of
      mortality. CONCLUSION: Females had better survival as compared to males following
      THS. SBP was an independent predictor of mortality in females with THS.

PMID- 28515605
TI  - Influence of Admission Source on the Outcome of Patients in an Intensive Care
      Unit.
AB  - AIM OF THE STUDY: The admission in the Intensive Care Unit (ICU) occurs from
      various sources, and the outcome depends on a complex interplay of various
      factors. This observational study was undertaken to describe the epidemiology and
      compare the differences among patients admitted in a tertiary care ICU directly
      from the emergency room, wards, and ICUs of other hospitals. MATERIALS AND
      METHODS: A retrospective study was conducted on 153 consecutive patients admitted
      from various sources in a tertiary care ICU between July 2014 and December 2015.
      The primary endpoint of the study was the influence of the admission source on
      ICU mortality. The secondary endpoints were the comparison of the duration of
      mechanical ventilation, length of ICU stay, and the ICU complication rates
      between the groups. RESULTS: Out of the 153 patients enrolled, the mortality of
      patients admitted from the ICUs of other hospital were significantly higher than
      the patients admitted directly from the emergency room or wards/operating rooms
      (60.5% vs. 48.2% vs. 31.9%; P = 0.02). The incidence of ventilator-associated
      lung injury was lower in the patients admitted directly from the emergency room
      (23.4% vs. 50% vs. 50%; P = 0.03). Multivariate logistic regression analysis
      revealed higher age, increased disease severity, longer duration of mechanical
      ventilation, and longer ICU stay as independent predictors of mortality in the
      patients shifted from the ICUs of other hospitals. CONCLUSION: The study
      demonstrated a higher risk of ICU mortality among patients shifted from the ICUs
      of other hospitals and identified the independent predictors of mortality.

PMID- 28515607
TI  - Abrus precatorius Poisoning: A Retrospective Study of 112 Patients.
AB  - Abrus precatorius is a rare but important cause of plant poisoning, especially in
      tropical countries like India. Most of the published literature on Abrus is
      limited a few case reports. Hence, we did a retrospective study the clinical
      features and outcome of Abrus poisoning. Case records of patients admitted to
      medicine wards during 7 years were included in the study. A total of 112 patients
      were studied. The majority were females (78%), and most of the patients were
      between 13 and 30 years (81%). Diarrhea was the most common symptom (66%), and
      blood in stools was present in (33%). Six patients had died with a mortality rate
      of (5.35%).

PMID- 28515608
TI  - Thrombotic Thrombocytopenic Purpura in a Case of Dengue Fever: A Rare
      Presentation.
AB  - Here, we present an unusual occurrence of thrombotic thrombocytopenic purpura
      (TTP) in a case of dengue fever. Both the conditions are fatal and can result in
      significant mortality and morbidity if left untreated. In this case, as soon as,
      we diagnosed the patient as having TTP, we treated her with plasma exchange
      therapy, steroids, and monoclonal antibodies such as rituximab. The patient
      responded very well to the treatment and completely recovered from neurological
      symptoms and laboratory parameters also normalized. Hence, timely diagnosis and
      starting appropriate treatment immediately are key factors for successful
      outcome.

PMID- 28515609
TI  - Not all febrile critical illness with rash is infective: Drug reaction may be a
      mimic.
AB  - We report a case of ciprofloxacin-related drug rash with eosinophilia and
      systemic symptoms (DRESS) which was initially diagnosed and managed on the line
      of tropical fever. Later, a diagnosis of definite case of DRESS was made
      according to the RegiSCAR scoring system and the patient was managed with the
      removal of ciprofloxacin along with steroids. DRESS is a great masquerader. The
      diagnosis should be highly suspected in the presence of fever, skin rash, liver
      involvement, and hypereosinophilia.

PMID- 28515610
TI  - Hyperemia Causing Delayed Recovery in Traumatic Brain Injury.
AB  - Subarachnoid hemorrhage is a common manifestation of traumatic brain injury. A
      clinical deterioration in Glasgow Coma Scale score without an accompanying
      radiological worsening is suggestive of vasospasm. However, hyperemia could be
      another possibility which can easily be considered with corroborating
      transcranial Doppler (TCD) features. This case report reiterates the value of TCD
      in such instances.

PMID- 28515611
TI  - Malposition of the Central Venous Catheter: A Diagnostic Dilemma.
AB  - A 50-year-old male was admitted to Intensive Care Unit with head and chest injury
      needed multiple central venous catheter (CVC) for the long-term intravenous
      access. Right internal jugular vein was cannulated uneventfully, and the tip of
      CVC was confirmed in the chest radiograph along the right border of the
      mediastinum. After few days, left subclavian vein was cannulated and the
      procedure was uneventful. However, the postprocedure Chest X-ray showed the CVC
      along the left border of mediastinum rather than the right border. Possibility of
      CVC in one of the tributaries of left brachiocephalic vein was thought. Due to
      uncertainty in position of left CVC, we inserted CVC in right-sided subclavian
      vein, which was in normal position along the right border of mediastinum. Left
      subclavian CVC was removed. Reviewing the patient's thoracic computed tomography
      scan revealed, patient had congenital anomaly and double superior vena cava that
      explained the abnormal course of left subclavian CVC along the left border of
      mediastinum.

PMID- 28515612
TI  - Acute Yellow Phosphorus Poisoning Causing Fulminant Hepatic Failure with
      Parenchymal Hemorrhages and Contained Duodenal Perforation.
AB  - White phosphorus is well known as a potent hepatotoxin and a severe local and
      systemic toxin causing damage to gastrointestinal, hepatic, cardiovascular, and
      renal systems. It is used in the manufacture of matches, fireworks, rodenticide,
      and fertilizers. Death results due to acute liver failure. Management of yellow
      phosphorus (YP) poisoning is supportive with no antidote available. Here, we
      present a case of acute YP poisoning in a 25-year-old female presenting with
      fulminant hepatic failure and duodenal perforation.

PMID- 28515613
TI  - Secondary Sjogren's Syndrome Presenting with Distal Tubular Acidosis and
      Quadriparesis.
AB  - A 52-year-old female patient was admitted to Intensive Care Unit with complaints
      of quadriparesis. Investigations revealed distal renal tubular acidosis (DRTA)
      secondary to Sjogren's syndrome with involvement of the parotid and thyroid
      glands. Laboratory investigations showed hyperchloremic metabolic acidosis and an
      alkaline urine pH with clinical signs of sicca syndrome. Sjogren's syndrome is
      associated with DRTA and occurrences of quadriparetic hypokalemia,
      nephrolithiasis, and osteomalacia can be prevented with early diagnosis and
      lifelong treatment with potassium and alkali replacement.

PMID- 28515614
TI  - Symmetrical Peripheral Gangrene in Severe Plasmodium vivax Malaria.

PMID- 28515615
TI  - The Tissue Dilator: A Victim or the Aggressor?

PMID- 28515616
TI  - Fourier series of sums of products of ordered Bell and poly-Bernoulli functions.
AB  - In this paper, we study three types of sums of products of ordered Bell and poly
      Bernoulli functions and derive their Fourier series expansion. In addition, we
      express those functions in terms of Bernoulli functions.

PMID- 28515617
TI  - A modified subgradient extragradient method for solving monotone variational
      inequalities.
AB  - In the setting of Hilbert space, a modified subgradient extragradient method is
      proposed for solving Lipschitz-continuous and monotone variational inequalities
      defined on a level set of a convex function. Our iterative process is relaxed and
      self-adaptive, that is, in each iteration, calculating two metric projections
      onto some half-spaces containing the domain is involved only and the step size
      can be selected in some adaptive ways. A weak convergence theorem for our
      algorithm is proved. We also prove that our method has [Formula: see text]
      convergence rate.

PMID- 28515618
TI  - Existence of entire solutions of some non-linear differential-difference
      equations.
AB  - In this paper, we investigate the admissible entire solutions of finite order of
      the differential-difference equations [Formula: see text] and [Formula: see
      text], where [Formula: see text], [Formula: see text] are two non-zero
      polynomials, [Formula: see text] is a polynomial and [Formula: see text]. In
      addition, we investigate the non-existence of entire solutions of finite order of
      the differential-difference equation [Formula: see text], where [Formula: see
      text], [Formula: see text] are two non-constant polynomials, [Formula: see text],
      m, n are positive integers and satisfy [Formula: see text] except for [Formula:
      see text], [Formula: see text].

PMID- 28515619
TI  - Weighted inequalities for generalized polynomials with doubling weights.
AB  - Many weighted polynomial inequalities, such as the Bernstein, Marcinkiewicz,
      Schur, Remez, Nikolskii inequalities, with doubling weights were proved by
      Mastroianni and Totik for the case [Formula: see text], and by Tamas Erdelyi for
      [Formula: see text]. In this paper we extend such polynomial inequalities to
      those for generalized trigonometric polynomials. We also prove the large sieve
      for generalized trigonometric polynomials with doubling weights.

PMID- 28515620
TI  - Stationary acceleration of Frenet curves.
AB  - In this paper, the stationary acceleration of the spherical general helix in a 3
      dimensional Lie group is studied by using a bi-invariant metric. The relationship
      between the Frenet elements of the stationary acceleration curve in 4-dimensional
      Euclidean space and the intrinsic Frenet elements of the Lie group is outlined.
      As a consequence, the corresponding curvature and torsion of these curves are
      computed. In Minkowski space, for the curves on a timelike surface to have a
      stationary acceleration, a necessary and sufficient condition is refined.

PMID- 28515621
TI  - Inequalities for alpha-fractional differentiable functions.
AB  - In this article, we present an identity and several Hermite-Hadamard type
      inequalities for conformable fractional integrals. As applications, we establish
      some inequalities for certain special means of two positive real numbers and give
      the error estimations for the trapezoidal formula.

PMID- 28515622
TI  - The influence of genistein on free radicals in normal dermal fibroblasts and
      keloid fibroblasts examined by EPR spectroscopy.
AB  - Normal and keloid fibroblasts were examined using X-band (9.3 GHz) electron
      paramagnetic resonance spectroscopy. The effect of genistein on the concentration
      of free radicals in both normal dermal and keloid fibroblasts after ultraviolet
      irradiation was investigated. The highest concentration of free radicals was seen
      in keloid fibroblasts, with normal fibroblasts containing a lower concentration.
      The concentration of free radicals in both normal and keloid fibroblasts was
      altered in a concentration-dependent manner by the presence of genistein. The
      change in intra-cellular free radical concentration after the ultraviolet
      irradiation of both normal and keloid fibroblasts is also discussed. The
      antioxidant properties of genistein, using its 1,1-Diphenyl-2-picrylhydrazyl
      (DPPH) free radical-scavenging activity as a model, were tested, and the effect
      of ultraviolet irradiation on its interaction with free radicals was examined.
      The electron paramagnetic resonance spectra of DPPH showed quenching by
      genistein. The interaction of genistein with DPPH free radicals in the absence of
      ultraviolet irradiation was shown to be slow, but this interaction was much
      faster under ultraviolet irradiation. Ultraviolet irradiation enhanced the free
      radical-scavenging activity of genistein.

PMID- 28515623
TI  - Antibacterial properties of 5-substituted derivatives of rhodanine-3-carboxyalkyl
      acids.
AB  - A series of rhodanine 3-carboxyalkanoic acid derivatives possessing 4'-(N,N
      dialkyl-amino or diphenylamino)-benzylidene moiety as a substituent at the C-5
      position were synthesised and their antibacterial activity was screened. All the
      rhodanine derivatives showed bacteriostatic or bactericidal activity to the
      reference gram-positive bacterial strains, but lack of activity to the reference
      Gram-negative bacterial strains and yeast strains was observed.

PMID- 28515624
TI  - Closing the gap between plant ecology and Quaternary palaeoecology.
AB  - Ecology and Quaternary palaeoecology have largely developed as parallel
      disciplines. Although both pursue related questions, information exchange is
      often hampered by particularities of the palaeoecological data and a
      communicational gap has been perceived between the disciplines. Based on selected
      topics and developments mainly in Quaternary palaeoecology, we show that both
      disciplines have converged somewhat during recent years, while we still see
      untapped potential for closer interactions. Macroecology is probably the
      discipline that most easily combines different time-scales and where co
      operations between palaeoecologists, geneticists and vegetation modellers have
      been inspiring. Quantitative vegetation reconstructions provide robust estimates
      of tree composition and land cover at different spatial scales, suitable for
      testing hypotheses about long-term vegetation changes or as quantitative
      background data in studies on contemporary vegetation patterns. Palaeo-data also
      hold yet unexplored potential to study the drivers of long-term diversity and
      aspects of functional diversity may facilitate comparisons between continents and
      over glacial-interglacial cycles.

PMID- 28515625
TI  - Overview of the impact of Typhoid and Paratyphoid fever. Utility of Ty21a vaccine
      (Vivotif(r)).
AB  - Cases of diarrhoeal disease number from 1.7 to 5 billion per year worldwide. One
      of the main causes of diarrhoeal disease is typhoid fever, which is a potentially
      life-threatening multi-systemic illness. According to the most recent estimates,
      a total of 26.9 million typhoid fever episodes occurred in 2010. The geographical
      distribution of the disease differs widely; in developed countries, the incidence
      rate per 100,000 per year varies from < 0.1 to 0.3, and the disease mainly
      affects people who travel to endemic areas located in low- and middle-income
      countries. Low- and middle-income countries are mainly affected owing to the lack
      of clean water and proper sanitation. In the fight against this plague,
      prevention is fundamental, and vaccination against typhoid is an effective
      measure. Vivotif(r) is an oral live attenuated vaccine which contains a mutated
      strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine
      was first licensed in Europe in 1983 and in the US in 1989, and over the years it
      has proved efficacious and safe. It is indicated for adults and children from 5
      years of age upwards. Specifically, in the most developed countries, vaccination
      is suggested for highrisk population groups and particularly for international
      travellers to destinations where the risk of contracting typhoid fever is high.
      It must also be borne in mind that international travel is increasing. Indeed,
      international tourist arrivals totalled 1,184 million in 2015 and, on the basis
      of current trends, international travel is expected to grow by 3-4% in 2017.
      Vivotif(r) appears to be a powerful means of disease prevention, the importance
      of which is highlighted by the spread of antibiotic-resistant strains of
      Salmonella typhy (S. typhi).

PMID- 28515626
TI  - The history of tuberculosis: from the first historical records to the isolation
      of Koch's bacillus.
AB  - Tuberculosis (TB) is a contagious, infectious disease, due to Mycobacterium
      tuberculosis (MT) that has always been a permanent challenge over the course of
      human history, because of its severe social implications. It has been
      hypothesized that the genus Mycobacterium originated more than 150 million years
      ago. In the Middle Ages, scrofula, a disease affecting cervical lymph nodes, was
      described as a new clinical form of TB. The illness was known in England and
      France as "king's evil", and it was widely believed that persons affected could
      heal after a royal touch. In 1720, for the first time, the infectious origin of
      TB was conjectured by the English physician Benjamin Marten, while the first
      successful remedy against TB was the introduction of the sanatorium cure. The
      famous scientist Robert Koch was able to isolate the tubercle bacillus and
      presented this extraordinary result to the society of Physiology in Berlin on 24
      March 1882. In the decades following this discovery, the Pirquet and Mantoux
      tuberculin skin tests, Albert Calmette and Camille Guerin BCG vaccine, Selman
      Waksman streptomycin and other anti-tuberculous drugs were developed.

PMID- 28515628
TI  - Epidemiology of herpes simplex virus type 1 and 2 in Italy: a seroprevalence
      study from 2000 to 2014.
AB  - Herpes simplex viruses (HSV) are among the most widespread causative agents of
      human viral infections. HSV-2 is one of the commonest causes of genital disease,
      while HSV-1 is associated primarily with orolabial ulceration; however, recent
      changes in HSV epidemiology showed an increase in genital and neonatal herpes
      particularly caused by HSV-1. The main purpose of this study was to assess the
      seroprevalence of HSV-1 and HSV-2 in a random population in Siena (central Italy)
      in 2000, 2005 and 2013-2014 and in Bari (southern Italy) in 2005. Moreover, a
      preliminary study was conducted to investigate the spread of HSV infection in a
      population of pregnant women and infants in Bari in 2003, 2004 and 2005. Human
      serum samples were tested for the presence of specific anti-HSV-1 and anti-HSV-2
      IgG antibodies using a commercially available ELISA test. For the primary
      purpose, seroprevalence rates observed in Siena were compared over the years
      sampled and with the seroprevalence rate found in Bari. Results of seroprevalence
      in Siena show a decreased trend for both viruses, especially in adolescents and
      young adults; moreover, HSV-2 seroprevalence rates found in the two cities
      suggest geographical differences. For the secondary purpose, prevalence rates
      among pregnant women were compared with the seroprevalence found in women of the
      general population. No significant difference in prevalence rates were found
      among pregnant women, while results indicate both viruses are a source of
      infection in infants.

PMID- 28515629
TI  - Microbial competition in environmental nosocomial reservoirs and diffusion
      capacity of OXA48-Klebsiella pneumoniae: potential impact on patients and
      possible control methods.
AB  - BACKGROUND: We have found clusters of Klebsiella pneumoniae with OXA48
      carbepenemase cases in some hospital rooms, and decided to investigate whether
      bathroom siphons could be a reservoir for OXA48 bacteria, as occurs with K.
      oxytoca with other types of carbepenemases. METHODS: We evaluated the microbial
      competition between strains with OXA48 and VIM carbepenemases, in diluted
      nutrient-broth, on a slime germ-carrier. We compared the number of colonies at 5
      and 10 days on the contaminated carriers with one or two strains. We evaluated
      the dissemination of K. pneumoniae with carbepenemase OXA48 or VIM from thumbs
      and index fingers of volunteers, to standard surfaces (20 glass germ-carrier by
      each volunteer). After, we counted the number of microorganisms on each carrier.
      Microbiological weekly studies of faecal microbiota of all patients were obtained
      in Traumatology and Oncology. Moreover, we studied samples of the sink in their
      rooms. PCR and MLST sequence-type was determined in all K. pneumoniae diagnosed
      from patients and sinks. RESULTS: A large possibility of diffusion from
      contaminated hands, which continue to transmit high numbers of microorganisms
      after more than 10 successive surface contacts, was highlighted; OXA bacteria
      were more persistent than VIM bacteria. Microbial competition studies showed that
      VIM bacteria are inhibited by OXA ones. These observations can explain the
      concentration of cases of K. pneumoniae OXA48 in some rooms in Traumatology and
      Oncology, producing a significant OR between rooms with OXA48-bacteria
      contaminated siphons and other rooms (3.1 and 3.3 respectively). Risk was lowered
      after changing or disinfecting (heat plus chlorinated disinfectant) the
      contaminated siphons. Siphon colonization by VIM bacteria was not related with
      human infections by similar microorganisms. CONCLUSIONS: Bathroom siphons can be
      a reservoir for K. pneumoniae OXA48 and lead to outbreaks. Outbreaks can be
      controlled by replacement or heat plus chemical treatment of the sink-siphons.

PMID- 28515627
TI  - Frequently asked questions on seven rare adverse events following immunization.
AB  - Routine mass immunization programs have contributed greatly to the control of
      infectious diseases and to the improvement of the health of populations. Over the
      last decades, the rise of antivaccination movements has threatened the advances
      made in this field to the point that vaccination coverage rates have decreased
      and outbreaks of vaccine-preventable diseases have resurfaced. One of the
      critical points of the immunization debate revolves around the level of risk
      attributable to vaccination, namely the possibility of experiencing serious and
      possibly irreversible adverse events. Unfortunately, the knowledge about adverse
      events, especially rare ones, is usually incomplete at best and the attribution
      of a causal relationship with vaccinations is subject to significant
      uncertainties. The aim of this paper is to provide a narrative review of seven
      rare or very rare adverse events: hypotonic hyporesponsive episode, multiple
      sclerosis, apnea in preterm newborns, Guillain-Barre syndrome, vasculitides,
      arthritis/ arthralgia, immune thrombocytopenic purpura. We have selected these
      adverse events based on our experience of questions asked by health care workers
      involved in vaccination services. Information on the chosen adverse events was
      retrieved from Medline using appropriate search terms. The review is in the form
      of questions and answers for each adverse event, with a view to providing useful
      and actionable concepts while not ignoring the uncertainties that remain. We also
      highlight in the conclusion possible future improvements to adverse event
      detection and assessment that could help identify individuals at higher risk
      against the probable future backdrop of ever-greater abandonment of compulsory
      vaccination policies.

PMID- 28515630
TI  - An exception to the rule "no association between antibiotic resistance and
      decreased disinfectant microbicidal efficacy": Orthophthalaldehyde (OPA) and
      Pseudomonas aeruginosa isolated from ICU and paraplegic patients.
AB  - BACKGROUND: Antibiotic resistance and decreased susceptibility to disinfectants
      are not usually associated in microorganisms, but we have found an exception to
      this rule: P. aeruginosa versus orthophthalaldehyde (OPA). METHODS: Bactericidal
      effect of OPA was measured at 10 minutes on endodoncy files contaminated with an
      ATCC strain (control) or 206 strains of P. aeruginosa recently isolated from 206
      ICU and paraplegic patients in a tertiary university hospital, in two consecutive
      years. RESULTS: Differences in bactericidal effect of OPA were found between the
      strains isolated each year (decreased susceptibility in the first period), but in
      both years the statistical differences (p < 0.05) were maintained according to
      whether the strains were "susceptible" to antibiotics, "resistant" (to one family
      of antibiotics) or "multi-resistant" (resistant to more than one family of
      antibiotics), exhibiting a reduction in their OPA susceptibility in parallel to
      an increase of their antibiotic resistance. In contrast, there were no
      differences depending on the type of sample (sputum, urine, faeces, pharynx) or
      of patient (paraplegic or ICU: adult, newborn, burn). Finally we selected 15
      strains with an OPA effect below 3.5 log10 at 10 minutes and repeated the study
      with an OPA exposure of 15 minutes. In these conditions OPA showed a total
      bactericidal effect on these P. aeruginosa strains. CONCLUSIONS: There was an
      association between antibiotic resistance and decreased OPA susceptibility. This
      normally does not require an increase in disinfection time, but, for endoscope
      disinfection or instruments from colonized/infected patients with
      resistant/multiresistant P. aeruginosa, we consider it better to use 15 min of
      OPA. Regular tests (e.g., once every 12 months) with germ-carriers, should be
      performed to assess ecological changes in susceptibility to high level
      disinfectants and must include not only ATCC strains, but also recently isolated
      microorganisms with different antibiotic sensitivities (susceptible, resistant
      and multi-resistant).

PMID- 28515631
TI  - Water and air ozone treatment as an alternative sanitizing technology.
AB  - AIMS: We investigated the effectiveness of ozone (aqueous and gaseous) treatment
      as an alternative sanitizing technology to common conventional disinfectants in
      reducing the microbial contamination of both water and air. METHODS: Ozone was
      added for 20 minutes to a well-defined volume of water and air by the system
      named "Ozonomatic(r)". The effectiveness of ozonation was determined by counting
      CFU/ m3 or ml of bacteria present in samples of air or water collected before
      (T0) and after (T1) the addition of ozone and comparing the microbial load of
      different bacteria present in ozonized and nonozonized samples. RESULTS: When the
      ozonisation equipment was located at 30 cm from the surface of the water in the
      bath tub in which the bacteria investigated were inoculated, the treatment was
      able to reduce the total microbial load present in the aerosol by 70.4% at a
      temperature of 36 degrees C for 48 hours. Conversely, at 22 degrees C for 5 days,
      only a modest decrease (9.1%) was observed. Escherichia coli and Pseudomonas
      aeruginosa were completely eliminated. A 93.9% reduction was observed for
      Staphylococcus aureus, followed by Streptococcus faecalis (25.9%). The addition
      of ozone to water was able to almost eliminate Staphylococcus aureus (98.9%
      reduction) and also to exert a strong impact on Legionella pneumophila (87.5%
      reduction). Streptococcus faecalis and Pseudomonas aeruginosa showed a decrease
      of 64.2% and 57.4%, respectively. Conversely, only a 26.4% reduction was observed
      for the bacterium Escherichia coli. This study showed that the addition of ozone
      in the air exerted a modest reduction on microbial load at 36 degrees C, whereas
      no effect was observed at 22 degrees C. CONCLUSIONS: Aqueous and gaseous ozone
      treatments were effective against microbial contaminants, reducing the CFU of the
      microorganisms studied. These results confirm the efficacy of the ozone
      disinfection treatment of both water and air; particularly, it constitutes an
      extremely promising alternative, allowing the possibility to reuse contaminated
      water.

PMID- 28515632
TI  - Effectiveness of hand hygiene education among a random sample of women from the
      community.
AB  - OBJECTIVE: The effectiveness of hand hygiene education was investigated by
      studying the hand hygiene awareness and bacterial hand contamination among a
      random sample of 170 women in the community. METHODS: Questionnaire was used to
      assess the hand hygiene awareness score, followed by swabbing of the dominant
      hand. Bacterial identification was done by conventional biochemical tests.
      RESULTS: Better hand hygiene awareness score was significantly associated with
      age, scarce bacterial growth and absence of potential pathogen (p < 0.05). Out of
      the 170 hand samples, bacterial growth was noted in 155 (91.2%), which included
      91 (53.5%) heavy growth, 53 (31.2%) moderate growth and 11 (6.47%) scanty growth.
      The presence of enteric bacteria was associated with long nails (49.4% vs 29.2%;
      p = 0.007; OR = 2.3; 95% CI: 1.25-4.44) while finger rings were associated with
      higher bacterial load (p = 0.003). Coliforms was significantly higher among women
      who had a lower hand hygiene awareness score, washed their hands at lower
      frequency (59.0% vs 32.8%; p = 0.003; OR = 2.9; 95% CI: 1.41-6.13) and used
      common soap as compared to antiseptic soaps (69.7% vs 30.3%, p = 0.000; OR =
      4.11; 95% CI: 1.67-10.12). CONCLUSIONS: Level of hand hygiene awareness among the
      participants was satisfactory but not the compliance of hand washing practice,
      especially among the elders.

PMID- 28515633
TI  - Association between type 2 diabetes mellitus and anthropometric measurements - a
      case control study in South India.
AB  - INTRODUCTION: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM).
      Clinical evidence indicates a stronger association of diabetes with central
      obesity than general obesity. The present study aimed to compare the association
      between type 2 diabetes mellitus and different anthropometric measurements and
      evaluate the usefulness of these measurements in clinical practice. METHODS: A
      case-control study was done among 102 individuals; of whom 51 cases included
      diagnosed T2DM (>= 20 years age) patients attending the Medicine out-patient
      consultation of a tertiary care hospital and 51 controls who were screen negative
      for T2DM and recruited from the local community. Various anthropometric
      measurements were used according to standard World Health Organization (WHO)
      protocols. Data was entered and analyzed using Statistical Package for Social
      Sciences (SPSS) version 15. RESULTS: The proportion of cases with Body Mass Index
      (BMI) >= 25 kg/m2 was 55% as compared to 22% of controls and this association was
      statistically significant (p < 0.05). The proportion of cases with high waist
      circumference cut-offs (WC) was 74.5% as compared to 45.1% healthy individuals
      and this association was also statistically significant (p < 0.05, OR = 3.56). A
      Receiver Operating Characteristic (ROC) curve for both gender revealed highest
      area under the curve for body mass index (area = 0.787). Body mass index had the
      best discriminatory power. Waist to hip ratio was not a sensitive marker
      especially for females. CONCLUSIONS: A strong association between obesity indices
      and diabetes was identified. BMI and WC could be used in clinical practice for
      suggesting life style modifications.

PMID- 28515634
TI  - Difference in quality of life and associated factors among the elderly in rural
      Vietnam.
AB  - BACKGROUND: In Vietnam today, many generations remain living together in a
      family. With escalating urbanization and population aging, mental health
      disorders and the quality of life (QoL) among the elderly are gradually
      presenting themselves as of great concern. The objective of this study was to
      examine gender differences in QoL and some associated factors among the elderly
      in rural Vietnam using the QoL scale of WHO (WHOQOL-BREF). METHODS: A cross
      sectional study using quantitative methods. RESULTS AND CONCLUSIONS: The
      proportion of the elderly men having higher level of QoL in physical health,
      psychological health and environment was higher than that of their women
      counterparts. Reversely, of those having medium and lower QoL, females made up a
      larger proportion than males. The overall QoL score in elderly men (75.32) was
      higher than that of women (72.32) and the same pattern was witnessed in all four
      domains of QoL. While higher QoL in elderly men was significantly correlated with
      5 factors, aged >= 80 years, following Buddhism and Christianity, having better
      connection and without illness in the past 6 months, these among female
      counterparts are aged >= 80 years, completing secondary level or above, having
      medium and high socioeconomic status and without illness in the last 6 months.

PMID- 28515636
TI  - Optic cup segmentation: type-II fuzzy thresholding approach and blood vessel
      extraction.
AB  - We introduce here a new technique for segmenting optic cup using two-dimensional
      fundus images. Cup segmentation is the most challenging part of image processing
      of the optic nerve head due to the complexity of its structure. Using the blood
      vessels to segment the cup is important. Here, we report on blood vessel
      extraction using first a top-hat transform and Otsu's segmentation function to
      detect the curves in the blood vessels (kinks) which indicate the cup boundary.
      This was followed by an interval type-II fuzzy entropy procedure. Finally, the
      Hough transform was applied to approximate the cup boundary. The algorithm was
      evaluated on 550 fundus images from a large dataset, which contained three
      different sets of images, where the cup was manually marked by six
      ophthalmologists. On one side, the accuracy of the algorithm was tested on the
      three image sets independently. The final cup detection accuracy in terms of area
      and centroid was calculated to be 78.2% of 441 images. Finally, we compared the
      algorithm performance with manual markings done by the six ophthalmologists. The
      agreement was determined between the ophthalmologists as well as the algorithm.
      The best agreement was between ophthalmologists one, two and five in 398 of 550
      images, while the algorithm agreed with them in 356 images.

PMID- 28515635
TI  - Changing the smoking habit: prevalence, knowledge and attitudes among Umbrian
      hospital healthcare professionals.
AB  - BACKGROUND: Health care professionals should work against smoking habit to
      promote a correct life style. This study aimed to evaluate smoking prevalence and
      attitudes towards tobacco among Umbrian hospital professionals in a period
      between 2006 and 2015, since the approbation of the law that ban smoking in
      hospitals and all public areas in 2003. METHODS: A cross-sectional study was
      carried out using a questionnaire administered in 2006, 2011 and 2015 to
      healthcare professionals. It consists of 53 multiple-choice questions. Potential
      predictors of current smoking habits were evaluated using univariate and
      multivariate logistic regression. RESULTS: The sample included 475 healthcare
      professionals. Current smokers constituted 34.53% of the sample and no
      significant difference (p = 0.257) emerged in prevalence over time (33.74% in
      2006; 36.02% in 2011 and 33.77% in 2015). The risk of being a smoker increased by
      not considering the smoking habit as the main cause of preventable deaths (OR =
      2.25; 95% CI: 1.47- 3.45). The strongest risk factor, which was significant in
      both models (p < 0.01), was being against the "No Smoking" law (OR = 18.90; 95%
      CI: 2.43-147.71; adjusted OR = 22.10; 95% CI: 1.85-264.78). CONCLUSIONS: The
      hospital staff has higher prevalence of smoking than the general population. The
      No Smoking law alone has been shown to be inadequate. Effective results can be
      achieved only by a common strategy and shared intervention programmes that are
      based on a workplace health promotion strategy. That for the moment has
      demonstrated to give interesting outcomes in modifying deep-rooted behaviour
      patterns.

PMID- 28515637
TI  - Ultrasound biomicroscopy value in evaluation of restoration of ciliary muscles
      contractility after cataract extraction.
AB  - PURPOSE: To assess the changes in the contractility of the ciliary muscle in eyes
      with presbyopia before and after phacoemulsification and intracapsular lens
      implantation using ultrasound biomicroscopy (UBM). PATIENTS AND METHODS: This
      prospective study included 50 eyes of 30 consecutive subjects operated at the
      Department of Ophthalmology. Patients with any ocular disorder affecting visual
      acuity, corneal surface irregularities, had posterior capsular perforation or
      intensive postoperative corneal edema, or were <35 years of age, were excluded. A
      clear corneal phacoemulsification and posterior chamber intraocular lens were
      implanted. UBM was performed with and without instilling 2% pilocarpine. Ciliary
      body axial length (CBAXL), anterior chamber depth, and angle were measured before
      and 1 month after surgery. RESULTS: The CBAXL showed a greater contractile
      shortening (P<0.5), with centripetal, contractile shift of ciliary muscle mass.
      CONCLUSION: After phacoemulsification and intracapsular lens implantation,
      ultrasonic biomicroscopy showed significant centripetal movement of the ciliary
      body compared with that before surgery. This shows that a lenticular sclerotic
      component may influence both lens movement and the contractility of the ciliary
      muscle and is believed to be related to the presbyopia.

PMID- 28515638
TI  - Fatty Acid Profiles, Meat Quality, and Sensory Palatability of Grain-fed and
      Grass-fed Beef from Hanwoo, American, and Australian Crossbred Cattle.
AB  - Fatty acid profiles in relation to meat quality traits and sensory palatability
      of grain-fed and grass-fed beef from Hanwoo, American, and Australian crossbred
      cattle were examined in this study. There were significant (p<0.001) differences
      in fat content and fatty acid compositions between grain-fed and grass-fed beef.
      Grain-fed Hanwoo had significantly (p<0.001) lower saturated fatty acid (SFA)
      proportion but higher monounsaturated fatty acid (MUFA) proportion compared to
      grass-fed cattle. The proportion of oleic acid in grain-fed Hanwoo was
      significantly (p<0.001) higher than that in grass-fed Hanwoo, Australian
      crossbred, or American crossbred cattle. Grain-fed Hanwoo had significantly
      (p<0.001) lower percentages of drip loss and cooking loss compared to other
      cattle. Overall palatability panel scores of grain-fed cattle were significantly
      (p<0.001) higher than those of grass-fed cattle. Consequently, sensory overall
      palatability was negatively correlated with proportions of SFA and
      polyunsaturated fatty acid (PUFA), but positively correlated with the proportion
      of MUFA. In particular, the proportion of oleic acid was strongly and positively
      correlated with fat content (r=0.91, p<0.001) and overall palatability (r=0.92,
      p<0.001). These results implied that high-concentrate grain-fed could increase
      intramuscular fat (IMF) content and the proportion of oleic acid, thus increasing
      the sensory palatability of Hanwoo beef.

PMID- 28515639
TI  - Influence of Adding Recovered Protein from Processing Wastewater on the Quality
      of Mechanically Separated Chicken Meat Surimi Like-Material.
AB  - Functional and nutritional soluble proteins can be recovered from surimi (and
      surimi-like material) processing wastewater, reducing environmental problems and
      the cost of an irresponsible waste disposal. Recovered proteins may be added back
      at a low percentage to surimi products. The aim of this work was to evaluate the
      effect of the addition of soluble recovered proteins (RP), obtained from
      mechanically separated chicken meat surimi-like material (MSCM-SLM) processing
      wastewater by acidic pH-shifting, on the composition and texture of RP-MSCM-SLM,
      with RP contents of 0, 10, 20 and 30% (w/w) in the mixture. For that, proximate
      composition and gel properties were evaluated. The fat content of the MSCM-SLM
      was significantly reduced to 11.98% and protein increased to 83.64% (dry basis)
      after three washing cycles. The addition of 30% RP in the MSCM-SLM significantly
      augmented the protein content to 93.45% and reduced fat content from to 2.78%. On
      the other hand, the addition of RP was responsible for a drastic decrease in
      texture parameters, reaching 252.36 g, 185.23 g.cm, and 6.97 N for breaking
      force, gel strength and cutting strength, respectively, when 30% of RP was
      included in the MSCM-SLM. It was concluded that the obtained intermediary product
      (RP-MSCM-SLM) is a good option to applications in processed meat products where
      high texture parameters are dispensable, e.g., emulsified inlaid frankfurter-type
      sausages, but high protein content and low fat content desired.

PMID- 28515640
TI  - Carcass and Meat Characteristics and Gene Expression in Intramuscular Adipose
      Tissue of Korean Native Cattle Fed Finishing Diets Supplemented with 5% Palm Oil.
AB  - We hypothesized that supplementing finishing diets with palm oil would promote
      adipogenic gene expression but depress stearoyl-CoA desaturase (SCD) gene
      expression in intramuscular (i.m.) adipose tissues of Hanwoo steers during
      fattening period (from 16 to 32 mon of age). Fourteen Hanwoo steers were allotted
      randomly to 2 groups of 7 steers based on initial BW and fed either a basal diet
      (control) or the basal diet supplemented with 5% palm oil (BDSP). At slaughter,
      i.m. adipose tissue was harvested for analysis of adipogenic gene expression and
      fatty acid composition. There were no differences in BW or average daily gain
      between treatment groups. Supplemental palm oil had no effect on carcass quality
      traits (carcass weight, backfat thickness, loin muscle area, or marbling scores)
      or meat color values. Palm oil increased (p<0.05) expression of AMP-activated
      protein kinase-alpha and peroxisome proliferator-activated receptor-gamma, but
      decreased (p<0.05) CAAT/enhancer binding protein-beta gene expression and tended
      to decrease stearoyl-CoA desaturase gene expression in i.m. adipose tissue. Palm
      oil increased total i.m. polyunsaturated fatty acids (p<0.05) compared to the
      control i.m. adipose tissue, but had no effect on saturated or monounsaturated
      fatty acids. Although there were significant effects of supplemental palm oil on
      i.m. adipose tissue gene expression, the absence of negative effects on carcass
      and meat characteristics indicates that palm oil could be a suitable dietary
      supplement for the production of Hanwoo beef cattle.

PMID- 28515641
TI  - Molecular Typing and Antimicrobial Susceptibility of Staphylococcus aureus
      Strains Isolated from Raw Milk, Cheese, Minced Meat, and Chicken Meat Samples.
AB  - The objectives of this study were: i) to detect the presence of Staphylococcus
      aureus and methicillin-resistant S. aureus (MRSA) in raw milk, cheese, beef
      minced meat, and chicken meat samples; ii) to evaluate the antimicrobial
      susceptibility of the isolates; and iii) to determine clonal relation among the
      isolates by using pulsed-field gel electrophoresis (PFGE) method. Therefore, a
      total of 160 food samples were randomly collected between August 2014 and May
      2015 in Hatay province, located in the southern Turkey. Twenty (12.5%) of the
      samples were found to be contaminated with S. aureus. A total of 40 isolates from
      the 20 positive samples were confirmed to be S. aureus by multiplex PCR based on
      16S rRNA and nuc gene. The mec A gene was not detected in any of the S. aureus
      strains. In the present study, 39 out of 40 (97.5%) isolates were found to be
      resistant to one or more antibiotics. All of isolates were susceptible to
      gentamicin, oxacillin, and vancomycin. The highest resistance rate was detected
      in penicillin (95%) and ampicillin (92.5%), followed by tetracycline (30%),
      erythromycin (20%), ciprofloxacin (12.5%). Nine major patterns were determined by
      PFGE. In 6 of these patterns, thirty-six strains (90%) had identical PFGE
      profiles.

PMID- 28515642
TI  - Physicochemical and Functional Characterization of Blue-Shelled Eggs in Korea.
AB  - The aim of this study was to compare the quality and physicochemical
      characteristics of blue-shelled eggs (BE) and conventional eggs (CE). Proximate
      composition, quality, pH value, shell color, collagen content, fatty acid
      composition, total cholesterol, alpha-glucosidase inhibition activity, and
      antioxidation activity were determined. The proximate composition, general
      qualities, and pH values of CE and BE showed no significant differences, except
      in moisture composition, weight, and shell thickness. Moisture content and weight
      of BE were significantly lower than those of CE. However, shell thickness and
      weight of BE were higher than those of CE (p<0.05). Lightness of BE was
      significantly higher than that of CE (85.20 vs. 58.80), while redness (a*) and
      yellowness (b*) of BE were lower than those of CE (a*: -4.75 vs. 14.20; b*: 10.45
      vs. 30.63). The fatty acid [C18:1n7 (cis-vaccenic acid) and C18:3n6 (gamma
      linolenic acid)] contents of BE were significantly higher than those of CE. The
      total cholesterol contents of BE and CE were similar. DPPH radical scavenging
      activity of BE was significantly higher than that of CE (40.78 vs. 35.35).
      Interestingly, alpha-glucosidase inhibition activity of whole egg and egg yolk in
      BE (19.27 and 36.06) was significantly higher than that of whole egg and egg yolk
      in CE (13.95 and 32.46). This result indicated that BE could potentially be used
      as a functional food material. Further studies are required to evaluate the
      specific compounds that affect functional activity.

PMID- 28515643
TI  - Quality of Frozen Pork from Pigs Fed Diets Containing Palm Kernel Meal as an
      Alternative to Corn Meal.
AB  - The objective of this study was to evaluate the effect of different levels of
      palm kernel meal (PKM), an alternative to corn, on the quality of pork. A total
      of 72 crossbred pigs ([Yorkshire * Landrace] * Duroc) were assigned into four
      dietary treatments (PKM level of 0, 4, 8, or 12%). After 12 wk, one pig of median
      weight in each pen was selected and slaughtered to analyze meat quality. The
      color, free radical scavenging activity, lipid oxidation, texture, composition of
      fatty acids, and sensory qualities of pork loin were evaluated post slaughter.
      When the levels of PKM in the diet increased, the L*-value of pork loin
      decreased, whereas a*-value and total saturated fatty acids increased. 2
      Thiobarbituric acid reactive substance (TBARS) values of pork loin were lower in
      groups treated with 8 and 12% PKM than in the control group at day 0; this
      difference, however, was not observed at day 3 and 7. The results of texture
      analysis showed that increasing the PKM ratio decreased hardness, chewiness, and
      springiness at day 7. The sensory test, however, indicated no differences between
      the control and treated groups. These findings show that finisher pigs could
      tolerate PKM as a replacement for corn; PKM did not negatively affect the quality
      of pork, indicating that it can be utilized as feed.

PMID- 28515644
TI  - Effects of Bundle Type and Substitution with Spent Laying Hen Surimi on Quality
      Characteristics of Imitation Crabsticks.
AB  - The purpose of this study was to evaluate the effects of bundle type (BT) and
      substitution with spent laying hen (SH) surimi on quality characteristics of
      imitation crabsticks made from Alaska Pollack (AP) during 6 wk of cold storage.
      Diagonally bundled samples had poorer gel characteristics and more lipid
      oxidation when compared with straight bundled ones (p<0.05). The color of
      diagonally bundled imitation crabsticks deteriorated with storage time (p<0.01).
      However, BT did not affect sensory characteristics (p>0.05). SH substitution had
      an effect on most quality characteristics of imitation crabsticks; darker and
      poorer gel characteristics were observed and its effect on sensory evaluation was
      seen at the initial storage. Thus, BT and SH substitution can be considered to
      have a slight effect on eating quality of imitation crabsticks, despite their
      negative effects on color, gel characteristics, and lipid oxidation.

PMID- 28515645
TI  - Effect of Abalone Hydrolysates Encapsulated by Double Emulsion on the
      Physicochemical and Sensorial Properties of Fresh Cheese.
AB  - The intake of dietary salt through food now exceeds current nutritional
      recommendations and is thought to have negative effects on human health, such as
      the increasing prevalence of hypertension. This study was performed to
      investigate whether W1/O/W2 double emulsions can be used to enhance the saltiness
      of cheese without increasing the salt content (W1 is distilled water or 1%
      abalone hydrolysate, and W2 is 1% NaCl or 1% abalone hydrolysate + 1% NaCl
      solution). We also investigated the effect of adding abalone hydrolysate to the
      double emulsion as a saltiness enhancer. The cheeses were physico-chemically
      evaluated to determine curd yield, pH value, moisture content, color, texture,
      salt release rate, and sensory properties. No significant differences were
      observed in curd yield, pH value, moisture content, lightness, or redness between
      the cheeses made with and without the double emulsion. However, in the evaluation
      of salt release rate, fresh cheese made with double emulsion (W1 = distilled
      water, W2 = 1% NaCl + 1% abalone hydrolysate) was detected earlier than the
      control or the other treatments. In the sensory evaluation, fresh cheese made
      with the double emulsion showed higher scores for saltiness and overall
      preference than the control or the other treatments. We concluded that abalone
      hydrolysate encapsulated in a double emulsion (W1 is water and W2 is abalone
      hydrolysate and NaCl solution) could enhance the saltiness of fresh cheese while
      maintaining the same salt concentration, without altering its physical
      properties.

PMID- 28515647
TI  - Comparative Study on Compositions and Functional Properties of Porcine, Chicken
      and Duck Blood.
AB  - Hematological, chemical and functional characteristics of porcine, chicken and
      duck blood were evaluated. A porcine blood sample showed the most abundant red
      blood cell, hemoglobin concentration, packed cell volume and plasma protein
      content as well as its freeze-dried blood possessed the highest contents of
      protein, fat, Cu and Cr with the highest percentage of heme iron (p<0.05). Unlike
      porcine blood, chicken blood showed a well balance in some essential amino acids,
      specifically for a higher isoleucine content (p<0.05). Furthermore, it possessed
      the highest contents of carbohydrate, Zn and non-heme iron (p<0.05). The most
      rapid response to form a strong gel, especially at 70 degrees C and 80 degrees C,
      was found in chicken blood, followed by duck and porcine blood, respectively. The
      result of emulsion activity index (EAI) and emulsion stability index (ESI) at the
      low protein concentration indicated that chicken blood had the most superior
      emulsion properties (p<0.05). Regarding duck blood, it exhibited the highest
      content of Mg and Mn (p<0.05). Moreover, duck blood had similar foaming
      properties to porcine blood in which they showed higher values than chicken blood
      (p<0.05). Specific characteristics of blood were therefore diminished by animal
      species in which this information could be used as food supplementation or
      product development based on their potential applications.

PMID- 28515646
TI  - Lotus (Nelumbo nucifera) Rhizome as an Antioxidant Dietary Fiber in Cooked
      Sausage: Effects on Physicochemical and Sensory Characteristics.
AB  - The objective of this study was to determine the physicochemical and sensory
      properties of cooked emulsion sausages containing different levels of lotus
      rhizome powder (0, 1, 2, and 3%, based on total weight). Lotus rhizome powder had
      no significant (p>0.05) impact on pH, moisture, protein, or ash content of
      sausage. However, fat content was slightly but significantly (p<0.05) decreased
      when the level of lotus rhizome powder was increased in the sausages. The
      addition of lotus rhizome powder to sausages at over 1% resulted in significantly
      (p<0.05) darker and less red color of cooked sausage compared to control.
      Increase in lotus rhizome level slightly improved the emulsion stability and
      apparent viscosity. Significant (p<0.05) reduction in cooking loss was observed
      when more than 1% of lotus rhizome powder was added to sausages. The textural
      properties of sausages were unaffected by the inclusion of lotus rhizome except
      for springiness and chewiness. On the manufacture day, control sausage had
      significantly (p<0.05) higher TBARS value than treatments. Regarding sensory
      characteristics, increased levels of lotus rhizome powder decreased (p<0.05)
      color and juiciness scores. However, cooked sausages exhibited similar overall
      acceptability regardless of the level of lotus rhizome powder added to sausages.
      Therefore, lotus rhizome powder, an antioxidant dietary fiber, could be used as
      an effective natural ingredient in meat products for the development of healthier
      and functional food.

PMID- 28515648
TI  - Evaluation of Antioxidative Activity of Various Levels of Ethanol Extracted
      Tomato Powder and Application to Pork Patties.
AB  - This study was performed to evaluate antioxidant activity of tomato powder
      extracted by various concentrations of ethanol (0, 25, 50, 75, 100%) and to
      evaluate the physicochemical properties and antioxidant activities of pork
      patties with ethanol extracted tomato (EET) powder. No differences in the
      contents of total of individual phenolic compounds including gallic acid and
      catechin, were observed among the treatments (p>0.05). Among the various
      concentrations, 50% and 75% EET powder showed the highest free radical scavenging
      and iron chelating activities (p<0.05). Lipid peroxidation was retarded in
      linoleic acid emulsion with the addition of 50% and 75% EET powder (0.1%). Based
      on the model study, five pork patties were actually manufactured; control patty,
      reference patty with 0.01% of butylated hydroxytoluene, patty with 1% of water
      extracted tomato (WET), and patties with 0.5 and 1.0% of EET. Addition of 1% WET
      and EET decreased pH value, and increased redness values of pork patties, as
      compared to the control (p<0.05). Pork patties with WET (1.0%) and EET (0.5% and
      1.0%) had lower 2-thiobarbituric acid reactive substances values compared with
      control patties after 7 d of storage (p<0.05). Pork patties containing EET powder
      showed lower total bacterial and Enterobacteriaceae counts than control patties
      (p<0.05). In conclusion, WET and EET (50%) could be used as a natural antioxidant
      and antimicrobial agent in meat products.

PMID- 28515649
TI  - Effect of Persimmon Peel (Diospyros kaki Thumb.) Extracts on Lipid and Protein
      Oxidation of Raw Ground Pork During Refrigerated Storage.
AB  - The inhibition effect of persimmon peel extracts (PPE) (0.05(PPE-0.05), 0.1(PPE
      0.1), and 0.2 g(PPE-0.2) per meat sample) on lipid and protein oxidation of pork
      patties during chilled storage for 12 days were investigated and compared to
      ascorbic acid (As-0.05) and butylhydroxytoluene (BHT) (BHT-0.01). The meat
      samples treated with PPE had greater (p<0.05) a* values comparing control in raw
      pork patties meat from day 4 of storage. The addition of PPE at all
      concentrations on meat samples effectively inhibited the formation of oxidation
      products as shown by decreasing conjugated dienes (CD), peroxide values (POVs),
      thiobarbituric acid reaction substances (TBARS), and carbonyl content during
      chilled storage for 12 d. The PPE-0.2 and BHT-0.01 had the lowest in decrease
      rate of free thiol content (0.24 and 0.22 times) during chilled storage.
      Therefore, results of this study suggest that PPE can be considered a potential
      antioxidant against lipid and protein oxidation of raw meat products.

PMID- 28515650
TI  - Prevalence and Comparing of Some Microbiological Properties, Somatic Cell Count
      and Antibiotic Residue of Organic and Conventional Raw Milk Produced in Turkey.
AB  - The aim of this study was to investigate the effects of production systems and
      milk collection periods on the somatic cell count (SCC), some microbiological
      properties, total aerobic mesophilic bacteria (TAMB), coliform, Staphylococcus
      aureus (S. aureus), yeast and mould) and antibiotic residue of milk; in Turkey.
      Milk samples were collected from 9 conventional farms and 9 organic farms during
      one year time, at six different months (December 2013 to October 2014), and all
      farms were selected from the same geographical locations. All organically managed
      farms had organic production certificates given by the Republic of Turkey
      Ministry of Food, Agriculture and Livestock. The count of TAMB, coliform, and
      coagulase positive S. aureus were affected by production systems at the level of
      p<0.01; yeast and mold, and somatic cell count (SCC) were affected at the level
      of p<0.05. But, differences according to months were statistically significant
      only on TAMB (p<0.01) and coliform (p<0.05) counts. The general means of TAMB,
      coliform and yeast and mould counts of the organic milk (OM) were significantly
      lower (p<0.05), while the general means of SCC and coagulase positive S. aureus
      count of the OM was significantly higher (p<0.05) compared to conventional milk
      (CM). Antibiotic residue was determined in one of the CM sample and in two of the
      OM samples. Our study is the first research that compared conventional and
      organic milk in Turkey. This study indicated that the microbiological quality of
      OM was the higher in terms of TAMB, coliform and yeast and mould, whereas was the
      lower in relation to SCC and coagulase positive S. aureus counts. But, the
      quality of both milk types should be improved.

PMID- 28515651
TI  - Effect of Gleditsia sinensis Lam. Extract on Physico-Chemical Properties of
      Emulsion-Type Pork Sausages.
AB  - This study was performed to investigate the effect of Gleditsia sinensis Lam.
      extract on the physicochemical properties of emulsion-type pork sausages during
      storage at 10 degrees C for 4 wk. Treatments were as follows: (C, control; T1,
      sodium ascorbate 0.05%; T2, Gleditsia sinensis Lam. 0.05%; T3, Gleditsia sinensis
      Lam. 0.1%; T4, Gleditsia sinensis Lam. 0.2%; T5, Gleditsia sinensis Lam. 0.1% +
      sodium ascorbate 0.05%). The values of pH, moisture content, lightness, redness,
      and sensory attributes were all significantly decreased, while the yellowness,
      chroma, hue angle, and texture properties were increased during storage with
      increase of the Gleditsia sinensis Lam. extract added. In addition, the
      antioxidant activity and antimicrobial activity in the sausages displayed
      significant increases (p<0.05). Therefore, although it was concluded that the
      addition of Gleditsia sinensis Lam. extract is not effective for improvement of
      the physical properties compared to chemical additives in sausages, it could be
      applied to meat products as a natural preservatives.

PMID- 28515652
TI  - Effects of Pre-Converted Nitrite from Red Beet and Ascorbic Acid on Quality
      Characteristics in Meat Emulsions.
AB  - We investigated the effects of fermented red beet extract and ascorbic acid on
      color development in meat emulsions. The pH of meat emulsions containing red beet
      extract decreased with an increase in the amount of extract added. The redness of
      the treated meat emulsions was higher than that of the control with no added
      nitrite or fermented red beet extract (p<0.05), though the redness of the meat
      emulsions treated with fermented red beet extract only was lower than in that
      treated with both fermented red beet extract and ascorbic acid (p<0.05). The
      highest VBN, TBARS, and total viable count values were observed in the control,
      and these values in the meat emulsions treated with fermented red beet extract
      were higher than in that treated with both fermented red beet extract and
      ascorbic acid (p<0.05). E. coli and coliform bacteria were not found in any of
      the meat emulsions tested. Treatment T2, containing nitrite and ascorbic acid,
      had the highest overall acceptability score (p<0.05); however, there was no
      significant difference between the T2 treatment and the T6 treatment, which
      contained 10% pre-converted nitrite from red beet extract and 0.05% ascorbic acid
      (p>0.05). The residual nitrite content of the meat emulsions treated with
      ascorbic acid was lower than in those treated without ascorbic acid (p<0.05).
      Thus, the combination of fermented red beet extract and ascorbic acid could be a
      viable alternative to synthetic nitrite for the stability of color development in
      meat emulsions.

PMID- 28515653
TI  - Assessment of Microbial and Radioactive Contaminations in Korean Cold Duck Meats
      and Electron-Beam Application for Quality Improvement.
AB  - Animal-origin food products pose serious threat to public food safety due to high
      microbial loads. The microbial and radioactive contaminations in commercial cold
      duck meat products were evaluated. Ten different lots of commercial samples (C1
      C10) were classified based on type and smoking process. All samples were highly
      contaminated (< 4-7 Log CFU/g) with total aerobic bacteria (TAB), yeasts and
      molds (Y&M), and 7 samples (C1-C7) were positive for coliforms. Furthermore,
      three samples were contaminated with Listeria monocytogenes (C4-C6) and one with
      Salmonella typhimurium (C6). No radionuclides (131I, 137Cs, and 134Cs) were
      detected in any sample. The results of DEFT (direct epifluorescent filter
      technique)/APC (aerobic plate count), employed to screen pre-pasteurization
      treatments of products, indicated that smoked samples were positive showing
      DEFT/APC ratios higher than 4. Notably, the samples showed a serious threat to
      microbial safety, thus were irradiated with electron-beam (e-beam). The D10
      values for S. typhimurium and L. monocytogenes were 0.65 and 0.42 kGy,
      respectively. E-beam application at 3 and 7 kGy resulted in reduction of initial
      TAB, Y&M, and coliform populations by 3 and 6 log cycles, respectively. Thus, e
      beam was proven to be a good decontamination approach to improve the hygiene of
      cold duck meat.

PMID- 28515654
TI  - Qualitative Characteristics and Determining Shelf-Life of Milk Beverage Product
      Supplemented with Coffee Extracts.
AB  - This study was conducted to establish the shelf-life of a milk beverage product
      supplemented with coffee extracts. Qualitative changes including peroxide value
      (PV), microorganism content, caffeine content, and sensory evaluation were
      measured periodically in beverages kept at 10, 20, and 30 degrees C for 8 wk.
      Lipid oxidation of the product was measured by peroxide value analysis, and
      apparent changes were observed during a 4 wk storage period. Caffeine analysis
      revealed that the changes in caffeine content were negligible during the storage
      period. Total aerobic bacteria, Escherichia coli, yeast, and mold were not
      detected in the products during an 8 wk storage period. Sensory evaluation
      revealed that after 4 wk of storage overall acceptance was less than 3 points on
      a 5-point scale. In this study, PV was used as an indicator of the shelf-life of
      the milk beverage product. PV analysis revealed that a value of 20 meq/kg was the
      end of the shelf-life using the Arrhenius equation and the accelerated shelf-life
      test (ASLT). Assuming that the beverages are kept at 4 degrees C during
      distribution, calculation of when the PV reached the quality limit point (20
      meq/kg) was done with the equation ln(PV) = 0.3644X - 2.21834 and, using that
      equation, PV = e0.3644X-2.21834 was calculated. Therefore, 14.3086 wk was
      determined to be the shelf-life of the milk beverage supplemented with coffee
      when stored at 4 degrees C.

PMID- 28515655
TI  - Effect of Calcium Lactate on Physico-Chemical Characteristics of Shank Bone
      Extract.
AB  - This study was conducted to develop calcium-fortified shank bone extract (SBE)
      and to determine the effect of adding calcium lactate on physico-chemical
      characteristics of SBE during cold storage. The following five experiment groups
      were used: Control (0%, no addition), T1 (0.05% calcium lactate), T2 (0.1%
      calcium lactate), T3 (0.5% calcium lactate), and T4 (1% calcium lactate). When
      the concentration of calcium lactate added to the SBE was increased, the pH,
      redness, and yellowness values were significantly reduced, whereas the salinity,
      sugar content, and turbidity of SBE were significantly increased. Sensory
      parameters such as aroma, flavor, and overall acceptability in the control, T1,
      and T2 had similar scores. The TBARS values of SBE was significantly increased
      when 1% of calcium lactate was added, and the VBN values of SBE with calcium
      lactate at day 7 were higher than that of control (p<0.05). However, the addition
      of calcium lactate showed an inhibition effect on the growth of total microbial
      counts in SBE until 4 d of storage. The calcium content of SBE was increased by
      the addition of calcium lactate in a dose-dependently manner. The proper addition
      level of calcium lactate in the SBE was determined to be 0.1%.

PMID- 28515657
TI  - Symposium on visualization in high-performance computing at SIGGRAPH Asia 2015.

PMID- 28515656
TI  - Isolation and Characterization of Listeria phages for Control of Growth of
      Listeria monocytogenes in Milk.
AB  - In this study, two Listeria bacteriophages, LMP1 and LMP7, were isolated from
      chicken feces as a means of biocontrol of L. monocytogenes. Both bacteriophages
      had a lytic effect on L. monocytogenes ATCC 7644, 15313, 19114, and 19115. Phages
      LMP1 and LMP7 were able to inhibit the growth of L. monocytogenes ATCC 7644 and
      19114 in tryptic soy broth at 10 degrees C and 30 degrees C. Nevertheless, LMP1
      was more effective than LMP7 at inhibiting L. monocytogenes ATCC 19114. On the
      contrary, LMP7 was more effective than LMP1 at inhibiting L. monocytogenes ATCC
      7644. The morphology of LMP1 and LMP7 resembled that of members of the
      Siphoviridae family. The growth of L. monocytogenes ATCC 7644 was inhibited by
      both LMP1 and LMP7 in milk; however, the growth of L. monocytogenes ATCC 19114
      was only inhibited by LMP1 at 30 degrees C. The lytic activity of bacteriophages
      was also evaluated at 4 degrees C in milk in order to investigate the potential
      use of these phages in refrigerated products. In conclusion, these two
      bacteriophages exhibit different host specificities and characteristics,
      suggesting that they can be used as a component of a phage cocktail to control L.
      monocytogenes in the food industry.

PMID- 28515658
TI  - Flow visualisation of a normal shock impinging over a rounded contour bump in a
      Mach 1.3 free-stream.
AB  - ABSTRACT: An experimental study has been conducted to visualise the instantaneous
      streamwise and spanwise flow patterns of a normal shock wave impinging over a
      rounded contour bump in a Mach 1.3 free-stream. A quartz-made transparent shock
      generator was used, so that instantaneous images could be captured during the oil
      flow visualisation experiments. Fluorescent oil with three different colours was
      used in the surface oil-flow visualisation experiment to enhance the
      visualisation of flow mixing and complicated flow features that present in the
      flow field. Experimental data showed that the rounded contour bump could split
      the impinging normal shock wave into a or a series of lambda-shaped shock wave
      structure(s). In addition, it was found that the flow pattern and the shock wave
      structures that appeared over the rounded contour bump depended highly on the
      impinging location of the normal shock wave. The flow pattern shown in this study
      agreed with the findings documented in literature. Moreover, it was observed from
      the instantaneous oil streaks that the normal shock impinging location also
      affected the size and the formation location of the spanwise counter-rotating
      vortices downstream of the bump crest. Finally, it was concluded that the
      terminating shock could distort the oil streaks that left over the surface of the
      contour bump. Therefore, the use of the transparent normal shock wave generator
      is recommended when conducting experiments with normal shock wave impingement
      involved. GRAPHICAL ABSTRACT: 

PMID- 28515659
TI  - The flow separation delay in the boundary layer by induced vortices.
AB  - ABSTRACT: A series of experiments involving the particle image velocimetry
      technique are carried out to analyse the quantitative effectiveness of the
      synthesized vortical structures towards actual flow separation control. The
      streamwise vortices are synthesized from the synthetic jet actuator and
      introduced into the attached and separating boundary layer developed on the flat
      plate surface. Two types of actuators with different geometrical set-ups are used
      to analyse the evolution of vortical structures in the near wall region and their
      impact towards achieving separation delay in the boundary layer. First, a single
      circular jet is synthesized by varying actuator operating parameters and issued
      into the boundary layer to evaluate the dynamics of the interaction between the
      vortical structures and the near wall low momentum fluid in the separated region.
      Second, an array of jets has been issued into the artificially separated region
      to assess the effectiveness of various vortical structures towards achieving the
      reattachment of the separated flow in the streamwise direction. GRAPHICAL
      ABSTRACT: 

PMID- 28515661
TI  - Improving Large Area Population Mapping Using Geotweet Densities.
AB  - Many different methods are used to disaggregate census data and predict
      population densities to construct finer scale, gridded population data sets.
      These methods often involve a range of high resolution geospatial covariate
      datasets on aspects such as urban areas, infrastructure, land cover and
      topography; such covariates, however, are not directly indicative of the presence
      of people. Here we tested the potential of geo-located tweets from the social
      media application, Twitter, as a covariate in the production of population maps.
      The density of geo-located tweets in 1x1 km grid cells over a 2-month period
      across Indonesia, a country with one of the highest Twitter usage rates in the
      world, was input as a covariate into a previously published random forests-based
      census disaggregation method. Comparison of internal measures of accuracy and
      external assessments between models built with and without the geotweets showed
      that increases in population mapping accuracy could be obtained using the
      geotweet densities as a covariate layer. The work highlights the potential for
      such social media-derived data in improving our understanding of population
      distributions and offers promise for more dynamic mapping with such data being
      continually produced and freely available.

PMID- 28515660
TI  - Environmental factors associated with the distribution of visceral leishmaniasis
      in endemic areas of Bangladesh: modeling the ecological niche.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a parasitic infection (also called
      kala-azar in South Asia) caused by Leishmania donovani that is a considerable
      threat to public health in the Indian subcontinent, including densely populated
      Bangladesh. The disease seriously affects the poorest subset of the population in
      the subcontinent. Despite the fact that the incidence of VL results in
      significant morbidity and mortality, its environmental determinants are
      relatively poorly understood, especially in Bangladesh. In this study, we have
      extracted a number of environmental variables obtained from a range of sources,
      along with human VL cases collected through several field visits, to model the
      distribution of disease which may then be used as a surrogate for determining the
      distribution of Phlebotomus argentipes vector, in hyperendemic and endemic areas
      of Mymensingh and Gazipur districts in Bangladesh. The analysis was carried out
      within an ecological niche model (ENM) framework using a maxent to explore the
      ecological requirements of the disease. RESULTS: The results suggest that VL in
      the study area can be predicted by precipitation during the warmest quarter of
      the year, land surface temperature (LST), and normalized difference water index
      (NDWI). As P. argentipes is the single proven vector of L. donovani in the study
      area, its distribution could reasonably be determined by the same environmental
      variables. The analysis further showed that the majority of VL cases were located
      in mauzas where the estimated probability of the disease occurrence was high.
      This may reflect the potential distribution of the disease and consequently P.
      argentipes in the study area. CONCLUSIONS: The results of this study are expected
      to have important implications, particularly in vector control strategies and
      management of risk associated with this disease. Public health officials can use
      the results to prioritize their visits in specific areas. Further, the findings
      can be used as a baseline to model how the distribution of the disease caused by
      P. argentipes might change in the event of climatic and environmental changes
      that resulted from increased anthropogenic activities in Bangladesh and
      elsewhere.

PMID- 28515662
TI  - TEMPO functionalized C60 fullerene deposited on gold surface for catalytic
      oxidation of selected alcohols.
AB  - C60TEMPO10 catalytic system linked to a microspherical gold support through a
      covalent S-Au bond was developed. The C60TEMPO10@Au composite catalyst had a
      particle size of 0.5-0.8 MUm and was covered with the fullerenes derivative of
      2.3 nm diameter bearing ten nitroxyl groups; the organic film showed up to 50 nm
      thickness. The catalytic composite allowed for the oxidation under mild
      conditions of various primary and secondary alcohols to the corresponding
      aldehyde and ketone analogues with efficiencies as high as 79-98%, thus giving
      values typical for homogeneous catalysis, while retaining at the same time all
      the advantages of heterogeneous catalysis, e.g., easy separation by filtration
      from the reaction mixture. The catalytic activity of the resulting system was
      studied by means of high pressure liquid chromatography. A redox mechanism was
      proposed for the process. In the catalytic cycle of the oxidation process, the
      TEMPO moiety was continuously regenerated in situ with an applied primary
      oxidant, for example, O2/Fe3+ system. The new intermediate composite components
      and the final catalyst were characterized by various spectroscopic methods and
      thermogravimetry. Graphical abstract?.

PMID- 28515668
TI  - Nested soft-collinear subtractions in NNLO QCD computations.
AB  - We discuss a modification of the next-to-next-to-leading order (NNLO) subtraction
      scheme based on the residue-improved sector decomposition that reduces the number
      of double-real emission sectors from five to four. In particular, a sector where
      energies and angles of unresolved particles vanish in a correlated fashion is
      redundant and can be discarded. This simple observation allows us to formulate a
      transparent iterative subtraction procedure for double-real emission
      contributions, to demonstrate the cancellation of soft and collinear
      singularities in an explicit and (almost) process-independent way and to write
      the result of a NNLO calculation in terms of quantities that can be computed in
      four space-time dimensions. We illustrate this procedure explicitly in the simple
      case of [Formula: see text] gluonic corrections to the Drell-Yan process of
      [Formula: see text] annihilation into a lepton pair. We show that this framework
      leads to fast and numerically stable computation of QCD corrections.

PMID- 28515664
TI  - Search for massive long-lived particles decaying semileptonically in the LHCb
      detector.
AB  - A search is presented for massive long-lived particles decaying into a muon and
      two quarks. The dataset consists of proton-proton interactions at centre-of-mass
      energies of 7 and 8 TeV, corresponding to integrated luminosities of 1 and
      2[Formula: see text], respectively. The analysis is performed assuming a set of
      production mechanisms with simple topologies, including the production of a Higgs
      like particle decaying into two long-lived particles. The mass range from 20 to
      80 [Formula: see text] and lifetimes from 5 to 100[Formula: see text] are
      explored. Results are also interpreted in terms of neutralino production in
      different R-Parity violating supersymmetric models, with masses in the 23-198
      GeV/[Formula: see text] range. No excess above the background expectation is
      observed and upper limits are set on the production cross-section for various
      points in the parameter space of theoretical models.

PMID- 28515671
TI  - Likelihood analysis of the minimal AMSB model.
AB  - We perform a likelihood analysis of the minimal anomaly-mediated supersymmetry
      breaking (mAMSB) model using constraints from cosmology and accelerator
      experiments. We find that either a wino-like or a Higgsino-like neutralino LSP,
      [Formula: see text], may provide the cold dark matter (DM), both with similar
      likelihoods. The upper limit on the DM density from Planck and other experiments
      enforces [Formula: see text] after the inclusion of Sommerfeld enhancement in its
      annihilations. If most of the cold DM density is provided by the [Formula: see
      text], the measured value of the Higgs mass favours a limited range of [Formula:
      see text] (and also for [Formula: see text] if [Formula: see text]) but the
      scalar mass [Formula: see text] is poorly constrained. In the wino-LSP case,
      [Formula: see text] is constrained to about [Formula: see text] and [Formula: see
      text] to [Formula: see text], whereas in the Higgsino-LSP case [Formula: see
      text] has just a lower limit [Formula: see text] ([Formula: see text]) and
      [Formula: see text] is constrained to [Formula: see text] in the [Formula: see
      text] ([Formula: see text]) scenario. In neither case can the anomalous magnetic
      moment of the muon, [Formula: see text], be improved significantly relative to
      its Standard Model (SM) value, nor do flavour measurements constrain the model
      significantly, and there are poor prospects for discovering supersymmetric
      particles at the LHC, though there are some prospects for direct DM detection. On
      the other hand, if the [Formula: see text] contributes only a fraction of the
      cold DM density, future LHC [Formula: see text]-based searches for gluinos,
      squarks and heavier chargino and neutralino states as well as disappearing track
      searches in the wino-like LSP region will be relevant, and interference effects
      enable [Formula: see text] to agree with the data better than in the SM in the
      case of wino-like DM with [Formula: see text].

PMID- 28515675
TI  - Utility of intraoral stents in external beam radiotherapy for head and neck
      cancer.
AB  - AIM: This study aimed to assess the utility and stability of intraoral stent
      during intensity-modulated radiation therapy (IMRT). BACKGROUND: The benefits of
      intraoral stents in radiotherapy are unclear. MATERIALS AND METHODS: We analyzed
      386 setup errors in 12 patients who received IMRT for head and neck cancers
      without intraoral stents (intraoral stent [-]) and 183 setup errors in 6 patients
      who received IMRT with intraoral stents (intraoral stent [+]). All patients were
      matched according to the immobilization method (masks and boards). Setup errors
      were measured as the distance from the initial setup based on the marking on the
      skin and mask to the corrected position based on bone matching on cone beam
      computed tomography. RESULTS: The mean interfractional setup errors in the right
      left, craniocaudal, anterior-posterior (AP), and three-dimensional (3D)
      directions were -0.33, 0.08, -0.25, and 2.75 mm in the intraoral stent (-) group
      and -0.37, 0.24, -0.63, and 2.42 mm in the intraoral stent (+) group,
      respectively (P = 0.50, 0.65, 0.01, and 0.02, respectively). The systematic
      errors for the same directions were 0.89, 1.46, 1.15, and 0.88 mm in the
      intraoral stent (-) group and 0.62, 1.69, 0.68, and 0.56 mm in the intraoral
      stents (+) group, respectively. The random errors were 1.43, 1.43, 1.44, and 1.22
      mm in the intraoral stent (-) group and 1.06, 1.11, 1.05, and 0.92 mm in the
      intraoral stents (+) group, respectively. CONCLUSION: Setup errors can be
      significantly reduced in the AP and 3D-directions by using intraoral stents.

PMID- 28515673
TI  - Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a
      hydroxyethyl chitosan/glycidyl methacrylate hydrogel.
AB  - BACKGROUND: Breast cancer negatively affects women's health worldwide. The tumour
      microenvironment plays a critical role in tumour initiation, proliferation, and
      metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures
      as monolayers on a flat solid surface lacking cell-cell and cell-matrix
      interactions. These experimental conditions deviate from the clinical situation.
      Improved experimental systems that can mimic the in vivo situation are required
      to discover new therapies, particularly for anti-angiogenic agents that mainly
      target intercellular factors and play an essential role in treating some cancers.
      METHODS: Chitosan can be modified to construct three-dimensional (3D) tumour
      models. Here, we report an in vitro 3D tumour model using a hydroxyethyl
      chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of
      chitosan modifications. Parameters relating to cell morphology, viability,
      proliferation, and migration were analysed using breast cancer MCF-7 cells. In a
      xenograft model, secretion of angiogenesis-related growth factors and the anti
      angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA
      hydrogels were assessed by immunohistochemistry. RESULTS: Hydroxyethyl
      chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure,
      mechanical properties, swelling ratio, and morphology consistent with a 3D tumour
      model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing
      in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a
      xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased
      secretion of angiogenesis-related growth factors. Recombinant human endostatin
      (Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent
      in HECS-GMA hydrogels. CONCLUSIONS: The HECS-GMA hydrogel provided a 3D tumour
      model that mimicked the in vivo cancer microenvironment and supported the growth
      of MCF7 cells better than traditional tissue culture plates. The HECS-GMA
      hydrogel may offer an improved platform to minimize the gap between traditional
      tissue culture plates and clinical applicability. In addition, the anti
      angiogenic efficacy of drugs such as Endostar and Bevacizumab can be more
      comprehensively studied and assessed in HECS-GMA hydrogels.

PMID- 28515678
TI  - Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating
      Metabotropic Glutamate Receptor 2.
AB  - Synaptic cell adhesion molecules represent important targets for neuronal
      activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans
      synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved
      from the cell surface by metalloproteases in an activity-dependent manner,
      releasing a soluble extracellular fragment and membrane-tethered C-terminal
      fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism
      by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are
      located primarily at the periphery of presynaptic terminals, where they inhibit
      the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress
      the release of glutamate and decrease synaptic transmission. In the present
      study, we found that the soluble ectodomain of NL1 binds to and activates mGluR2
      in both neurons and heterologous cells, resulting in a decrease in cAMP
      formation. In a slice preparation from the hippocampus of mice, NL1 inhibited the
      release of glutamate from mossy fibers that project to CA3 pyramidal neurons. The
      presynaptic effect of NL1 was abolished in the presence of a selective antagonist
      for mGluR2. Thus, our data suggest that the soluble extracellular domain of NL1
      functionally interacts with mGluR2 and thereby decreases synaptic strength.

PMID- 28515676
TI  - Low-Dose Dose-Response for In Vitro Nrf2-ARE Activation in Human HepG2 Cells.
AB  - Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-like
      factor 2-related factor 2 (Nrf2), and the antioxidant response element (ARE) are
      interacting components of a master regulatory signaling pathway that coordinates
      redox homeostasis, cytoprotective responses, and shifts in stem cell state. This
      study reexamined detailed dose-response (DR) data reported for in vitro Nrf2-ARE
      activation in human hepatoblastoma HepG2 cell lines containing either a ARE-bla
      or ARE-luc reporter at 12 different concentrations of each of 15 chemicals. The
      normalized study data were combined among chemicals exhibiting a positive
      response, yielding n = 531 (179) DR data for 9 (7) chemicals using the ARE-bla
      (ARE-luc) assay. Three-parameter linear/kth-power regression fits obtained to
      each combined set of ARE-bla- or ARE-luc-assay response data provided good fits
      (R2 = .99 or .91, respectively, Pfit > .99) that each incorporate a highly
      significant negative initial linear slope (P = 4 * 10-5 or .00025) and an overall
      J-shaped DR pattern. Results from this reanalysis of high-resolution ARE response
      data support the hypothesis that nonlinear ARE-mediated adaptive cellular
      responses to oxidative stress are governed by an ultrasensitive molecular switch.

PMID- 28515677
TI  - Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the
      Hypothalamus.
AB  - The polysialic acid (PSA) is a large glycan that is added to cell-surface
      proteins during their post-translational maturation. In the brain, PSA modulates
      distances between cells and controls the plasticity of the nervous system. In the
      hypothalamus, PSA is involved in many aspects of energy balance including food
      intake, osmoregulation, circadian rhythm, and sleep. In this work, we
      investigated the role of hypothalamic PSA in the regulation of plasma cholesterol
      levels and distribution. We report that HFD consumption in mice rapidly increased
      plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. Although plasma
      VLDL-cholesterol was normalized within the first week, LDL and HDL were still
      elevated after 2 weeks upon HFD. Importantly, we found that hypothalamic PSA
      removal aggravated LDL elevation and reduced HDL levels upon HFD. These results
      indicate that hypothalamic PSA controls plasma lipoprotein profile by
      circumventing the rise of LDL-to-HDL cholesterol ratio in plasma during
      overfeeding. Although mechanisms by which hypothalamic PSA controls plasma
      cholesterol homeostasis remains to be elucidated, these findings also suggest
      that low level of hypothalamic PSA might be a risk factor for dyslipidemia and
      cardiovascular diseases.

PMID- 28515679
TI  - Downregulation of the Repressor Element 1-Silencing Transcription Factor (REST)
      Is Associated with Akt-mTOR and Wnt-beta-Catenin Signaling in Prion Diseases
      Models.
AB  - Prion diseases are a group of infectious diseases characterized by multiple
      neuropathological changes, yet the mechanisms that preserve function and protect
      against prion-associated neurodegeneration are still unclear. We previously
      reported that the repressor element 1-silencing transcription factor (REST)
      alleviates neurotoxic prion peptide (PrP106-126)-induced toxicity in primary
      neurons. Here we confirmed the findings of the in vitro model in 263K infected
      hamsters, an in vivo model of prion diseases and further showed the relationships
      between REST and related signaling pathways. REST was depleted from the nucleus
      in prion infected brains and taken up by autophagosomes in the cytoplasm, co
      localizing with LC3-II. Importantly, downregulation of the Akt-mTOR and at least
      partially inactivation of LRP6-Wnt-beta-catenin signaling pathways correlated
      with the decreased levels of REST in vivo in the brain of 263K-infected hamsters
      and in vitro in PrP106-126-treated primary neurons. Overexpression of REST in
      primary cortical neurons alleviated PrP106-126 peptide-induced neuronal oxidative
      stress, mitochondrial damage and partly inhibition of the LRP6-Wnt-beta-catenin
      and Akt-mTOR signaling. Based on our findings, a model of REST-mediated
      neuroprotection in prion infected animals is proposed, with Akt-mTOR and Wnt-beta
      catenin signaling as the key pathways. REST-mediated neuronal survival signaling
      could be explored as a viable therapeutic target for prion diseases and related
      neurodegenerative diseases.

PMID- 28515682
TI  - Nitric Oxide Synthase Inhibitor Attenuates the Effects of Repeated Restraint
      Stress on Synaptic Transmission in the Paraventricular Nucleus of the Rat
      Hypothalamus.
AB  - Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine
      cells (PNCs) of the hypothalamic paraventricular nucleus (PVN) play a key role in
      the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Several
      studies have demonstrated that synaptic inputs to these cells may undergo stress
      related enhancement but, on the other hand, it has been reported that exposition
      to the same stressor for prolonged time periods may induce a progressive
      reduction in the response of the HPA axis to homotypic stressors. In the present
      study rats were subjected to 10 min restraint sessions, repeated twice daily for
      3 or 7 days. Miniature excitatory and inhibitory postsynaptic currents (mEPSCs
      and mIPSCs) were then recorded from PNCs in ex vivo hypothalamic slice
      preparations obtained 24 h after the last restraint. Restraint stress repeated
      over 3 days resulted in increased mean frequency and decreased rise time and
      decay time constant of mEPSCs, accompanied by a decrease in the excitability of
      PNCs, however, no such changes were evident in slices obtained from rats
      subjected to restraint over 7 days. There were no changes in mIPSCs after
      repeated restraint. Administration of the unspecific nitric oxide synthase (NOS)
      blocker Nomega-Nitro-L-arginine (L-NNA) before each restraint, repeated over 3
      days, prevented the occurrence of an increase in mEPSC frequency. However,
      animals receiving L-NNA and subjected to repeated restraint had similar changes
      in PNCs membrane excitability and mEPSC kinetics as stressed rats not receiving L
      NNA. Comparison of the effects of a single 10 min restraint session followed by
      either an immediate or delayed (24 h) decapitation revealed an increase in the
      mean mEPSC frequency and a decrease in the mean mIPSC frequency in slices
      prepared immediately after restraint, with no apparent effects when slice
      preparation was delayed by 24 h. These results demonstrate that restraint,
      lasting 10 min and repeated twice daily for 3 days, induces a selective and long
      lasting enhancement of excitatory synaptic input onto PNCs, partially by a NOS
      dependent mechanism, and reduces PNC excitability, whereas prolongation of
      repeated stress for up to 7 days results in an adaptation.

PMID- 28515681
TI  - The Activity-Induced Long Non-Coding RNA Meg3 Modulates AMPA Receptor Surface
      Expression in Primary Cortical Neurons.
AB  - Transcription of new RNA is crucial for maintaining synaptic plasticity, learning
      and memory. Although the importance of synaptic plasticity-related messenger RNAs
      (mRNAs) is well established, the role of a large group of long non-coding RNAs
      (lncRNAs) in long-term potentiation (LTP) is not known. In this study, we
      demonstrated the expression of a lncRNA cluster, namely maternally expressed gene
      3 (Meg3), retrotransposon-like gene 1-anti-sense (Rtl1-AS), Meg8 and Meg9, which
      is located in the maternally imprinted Dlk1-Dio3 region on mouse chromosome
      12qF1, in primary cortical neurons following glycine stimulation in an N-Methyl-D
      aspartate receptor (NMDAR)-dependent manner. Importantly, we also validated the
      expression of Meg3, Meg8 and Meg9 in the hippocampus of mice following cued fear
      conditioning in vivo. Interestingly, Meg3 is the only lncRNA that is expressed in
      the nucleus and cytoplasm. Further analysis revealed that Meg3 loss of function
      blocked the glycine-induced increase of the GluA1 subunit of AMPA receptors on
      the plasma membrane, a major hallmark of LTP. This aberrant trafficking of AMPA
      receptors correlated with the dysregulation of the phosphatidylinoside-3-kinase
      (PI3K)/AKT signaling pathway and the downregulation of the lipid phosphatase and
      tensin homolog (PTEN). These findings provide the first evidence for a functional
      role of the lncRNA Meg3 in the intricate regulation of the PTEN/PI3K/AKT
      signaling cascade during synaptic plasticity in neurons.

PMID- 28515680
TI  - Trk Receptors and Neurotrophin Cross-Interactions: New Perspectives Toward
      Manipulating Therapeutic Side-Effects.
AB  - Some therapeutic side-effects result from simultaneous activation of homolog
      receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC)
      play a major role in the development and biology of neurons through neurotrophin
      signaling. The wide range of cross-interactions between Trk receptors and
      neurotrophins vary in selectivity, affinity and function. In this study, we
      discuss new perspectives to the manipulation of side-effects via a better
      understanding of the cross-interactions at the molecular level, derived by
      computational methods. Available crystal structures of Trk receptors and
      neurotrophins are a valuable resource for exploitation via molecular mechanics
      (MM) and dynamics (MD). The study of the energetics and dynamics of neurotrophins
      or neurotrophic peptides interacting with Trk receptors will provide insight to
      structural regions that may be candidates for drug targeting and signaling
      pathway selection.

PMID- 28515674
TI  - Perioperative management of patients on direct oral anticoagulants.
AB  - Direct oral anticoagulants (DOACs) have been licensed worldwide for several years
      for various indications. Each year, 10-15% of patients on oral anticoagulants
      will undergo an invasive procedure and expert groups have issued several
      guidelines on perioperative management in such situations. The perioperative
      guidelines have undergone numerous updates as clinical experience of emergency
      management has increased and perioperative studies including measurement of
      residual anticoagulant levels have been published. The high inter-patient
      variability of DOAC plasma levels has challenged the traditional recommendation
      that perioperative DOAC interruption should be based only on the elimination half
      life of DOACs, especially before invasive procedures carrying a high risk of
      bleeding. Furthermore, recent publications have highlighted the potential danger
      of heparin bridging use when DOACs are stopped before an invasive procedure. As
      antidotes are progressively becoming available to manage severe bleeding or
      urgent procedures in patients on DOACs, accurate laboratory tests have become the
      standard to guide their administration and their actions need to be well
      understood by clinicians. This review aims to provide a systematic approach to
      managing patients on DOACs, based on recent updates of various perioperative
      guidance, and highlighting the advantages and limits of recommendations based on
      pharmacokinetic properties and laboratory tests.

PMID- 28515685
TI  - Pupillary Response to Negative Emotional Stimuli Is Differentially Affected in
      Meditation Practitioners.
AB  - Clinically, meditative practices have become increasingly relevant, decreasing
      anxiety in patients and increasing antibody production. However, few studies have
      examined the physiological correlates, or effects of the incorporation of
      meditative practices. Because pupillary reactivity is a marker for autonomic
      changes and emotional processing, we hypothesized that the pupillary responses of
      mindfulness meditation practitioners (MP) and subjects without such practices
      (non-meditators (NM)) differ, reflecting different emotional processing. In a
      group of 11 MP and 9 NM, we recorded the pupil diameter using video-oculography
      while subjects explored images with emotional contents. Although both groups
      showed a similar pupillary response for positive and neutral images, negative
      images evoked a greater pupillary contraction and a weaker dilation in the MP
      group. Also, this group had faster physiological recovery to baseline levels.
      These results suggest that mindfulness meditation practices modulate the response
      of the autonomic nervous system, reflected in the pupillary response to negative
      images and faster physiological recovery to baseline levels, suggesting that
      pupillometry could be used to assess the potential health benefits of these
      practices in patients.

PMID- 28515683
TI  - A Population of Projection Neurons that Inhibits the Lateral Horn but Excites the
      Antennal Lobe through Chemical Synapses in Drosophila.
AB  - In the insect olfactory system, odor information is transferred from the antennal
      lobe (AL) to higher brain areas by projection neurons (PNs) in multiple AL tracts
      (ALTs). In several species, one of the ALTs, the mediolateral ALT (mlALT),
      contains some GABAergic PNs; in the Drosophila brain, the great majority of
      ventral PNs (vPNs) are GABAergic and project through this tract to the lateral
      horn (LH). Most excitatory PNs (ePNs), project through the medial ALT (mALT) to
      the mushroom body (MB) and the LH. Recent studies have shown that GABAergic vPNs
      play inhibitory roles at their axon terminals in the LH. However, little is known
      about the properties and functions of vPNs at their dendritic branches in the AL.
      Here, we used optogenetic and patch clamp techniques to investigate the
      functional roles of vPNs in the AL. Surprisingly, our results show that specific
      activation of vPNs reliably elicits strong excitatory postsynaptic potentials
      (EPSPs) in ePNs. Moreover, the connections between vPNs and ePNs are mediated by
      direct chemical synapses. Neither pulses of GABA, nor pharmagological, or genetic
      blockade of GABAergic transmission gave results consistent with the involvement
      of GABA in vPN-ePN excitatory transmission. These unexpected results suggest new
      roles for the vPN population in olfactory information processing.

PMID- 28515686
TI  - Innate and Cultural Spatial Time: A Developmental Perspective.
AB  - We reviewed literature to understand when a spatial map for time is available in
      the brain. We carefully defined the concepts of metrical map of time and of
      conceptual representation of time as the mental time line (MTL) in order to
      formulate our position. It is that both metrical map and conceptual
      representation of time are spatial in nature. The former should be innate,
      related to motor/implicit timing, it should represent all magnitudes with an
      analogic and bi-dimensional structure. The latter MTL should be learned,
      available at about 8-10 years-old and related to cognitive/explicit time. It
      should have uni-dimensional, linear and directional structure (left-to-right in
      Western culture). We bear the centrality of the development of number cognition,
      of time semantic concepts and of reading/writing habits for the development of
      ordinality and linearity of the MTL.

PMID- 28515684
TI  - Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1
      Gene, a Risk Factor for Parkinson's Disease.
AB  - Parkinson's disease (PD), a neurodegenerative disorder, is accompanied by various
      non-motor symptoms including depression and anxiety, which may precede the onset
      of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B)
      inhibitor, and is widely used in the treatment of PD and major depression.
      However, there are few reports about the effects of selegiline on non-motor
      symptoms in PD. The aim of this study was to explore the antidepressant and
      anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a
      PD-related genetic model displaying depression and anxiety, compared with other
      antiparkinsonian drugs and an antidepressant, and was to investigate the effects
      of selegiline on biochemical parameters in emotion-related brain regions. A
      single administration of selegiline (1-10 mg/kg) dose-dependently reduced
      immobility time in the forced swimming test (FST) in CD157 KO mice, but not
      C57BL/6N wild-type (WT) mice. At 10 mg/kg, but not 3 mg/kg, selegiline
      significantly increased climbing time in CD157 KO mice. A single administration
      of the antiparkinsonian drugs pramipexole (a dopamine (DA) D2/D3 receptor
      agonist) or rasagiline (another MAO-B inhibitor), and repeated injections of a
      noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine, also
      decreased immobility time, but did not increase climbing time, in CD157 KO mice.
      The antidepressant-like effects of 10 mg/kg selegiline were comparable to those
      of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg
      rasagiline. After the FST, CD157 KO mice showed decreases in striatal and
      hippocampal serotonin (5-HT) content, cortical norepinephrine (NE) content, and
      plasma corticosterone concentration. A single administration of selegiline at 10
      mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to
      those observed in WT mice. In the open field test (OFT), repeated administration
      of mirtazapine had anxiolytic effects, and selegiline nonsignificantly
      ameliorated anxiety-like behaviors in CD157 KO mice. In the social interaction
      and preference tests, repeated mirtazapine ameliorated the high anxiety and low
      sociability of CD157 KO mice, whereas selegiline did not. These results indicate
      that selegiline has antidepressant and mild anxiolytic effects in CD157 KO mice,
      and suggest that it is an effective antiparkinsonian drug for depressive and
      anxiety symptoms in PD patients with a CD157 single nucleotide polymorphism
      (SNP).

PMID- 28515687
TI  - Effects of Passive Finger Movement on Cortical Excitability.
AB  - This study examined the effects of joint angle and passive movement direction on
      corticospinal excitability. The subjects were 14 healthy adults from whom consent
      could be obtained. We performed two experiments. In Experiment 1, we measured
      motor evoked potential (MEP) amplitude, F-wave and M-wave at 0 degrees  and 20
      degrees  adduction during adduction or abduction movement, in the range of
      movement from 10 degrees  abduction to 30 degrees  adduction. In Experiment 2,
      MEPs were measured at static 0 degrees  and 20 degrees  adduction during passive
      adduction from 10 degrees  adduction to 30 degrees  adduction and static 20
      degrees  adduction. MEP, F-waves and M-waves were recorded from the right first
      dorsal interosseous (FDI) muscle. Experiment 1 revealed significantly increased
      MEP amplitude at 0 degrees  during passive adduction compared to static 0 degrees
      (p < 0.01). No other significant differences in MEP, M-wave and F-wave
      parameters were observed. In Experiment 2, MEP amplitude was significantly higher
      at 20 degrees  adduction during passive adduction compared with static 0 degrees 
      (p < 0.01). Based on these findings, it appears that fluctuations in MEP
      amplitude values during passive movement are not influenced by joint angle, but
      rather it is possible that it is due to intracortical afferent facilitation (AF)
      dependent on afferent input due to the start of movement and interstimulus
      interval (ISI) of transcranial magnetic stimulation (TMS).

PMID- 28515689
TI  - Current Experimental Studies of Gene Therapy in Parkinson's Disease.
AB  - Parkinson's disease (PD) was characterized by late-onset, progressive dopamine
      neuron loss and movement disorders. The progresses of PD affected the neural
      function and integrity. To date, most researches had largely addressed the
      dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia
      hampered the use of the drug. And the mechanism of PD is so complicated that it's
      hard to solve the problem by just add drugs. Researchers began to focus on the
      genetic underpinnings of Parkinson's disease, searching for new method that may
      affect the neurodegeneration processes in it. In this paper, we reviewed current
      delivery methods used in gene therapies for PD, we also summarized the primary
      target of the gene therapy in the treatment of PD, such like neurotrophic factor
      (for regeneration), the synthesis of neurotransmitter (for prolong the duration
      of L-dopa), and the potential proteins that might be a target to modulate via
      gene therapy. Finally, we discussed RNA interference therapies used in
      Parkinson's disease, it might act as a new class of drug. We mainly focus on the
      efficiency and tooling features of different gene therapies in the treatment of
      PD.

PMID- 28515691
TI  - Corrigendum: Identification of Cerebral Metal Ion Imbalance in the Brain of
      Ageing Octodon degus.
AB  - [This corrects the article on p. 66 in vol. 9, PMID: 28405187.].

PMID- 28515692
TI  - Wu-Tou Decoction in Rheumatoid Arthritis: Integrating Network Pharmacology and In
      Vivo Pharmacological Evaluation.
AB  - Purpose: This study aimed to explore underlying action mechanism of Wu-Tou
      decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology
      prediction and experimental verification. Methods: Chemical compounds and human
      target proteins of WTD as well as RA-related human genes were obtained from TCM
      Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular
      networks and canonical pathways presumably involved in the treatment of WTD on RA
      were generated by ingenuity pathway analysis (IPA) software. Furthermore,
      experimental validation was carried out with MIP-1beta-induced U937 cell model
      and collagen induced arthritis (CIA) rat model. Results: CCR5 signaling pathway
      in macrophages was shown to be the top one shared signaling pathway associated
      with both cell immune response and cytokine signaling. In addition, protein
      kinase C (PKC) delta and p38 in this pathway were treated as target proteins of
      WTD in RA. In vitro experiments indicated that WTD inhibited MIP-1beta-induced
      production of TNF-alpha, MIP-1alpha, and RANTES as well as phosphorylation of
      CCR5, PKC delta, and p38 in U937 cells. WTD treatment maintained the inhibitory
      effects on production of TNF-alpha and RANTES in MIP-1beta-induced U937 cells
      after CCR5 knockdown. In vivo experiments demonstrated that WTD ameliorated
      symptoms in CIA rats, decreased the levels of IL-1beta, IL-2, IL-6, TNF-alpha,
      MIP-1alpha, MIP-2, RANTES, and IP-10 in serum of CIA rats, as well as mRNA levels
      of MIP-1alpha, MIP-2, RANTES, and IP-10 in ankle joints of CIA rats. Furthermore,
      WTD also lowered the phosphorylation levels of CCR5, PKC delta and p38 in both
      ankle joints and macrophages in ankle joints from CIA rats. Conclusion: It was
      demonstrated in this research that WTD played a role in inhibiting inflammatory
      response in RA which was closely connected with the modulation effect of WTD on
      CCR5 signaling pathway in macrophages.

PMID- 28515688
TI  - Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in
      Alzheimer's Disease.
AB  - Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease
      (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the
      many well-validated metrics for systemic IR, the absence of biomarkers for brain
      specific IR represents a translational gap that has hindered its study in living
      humans. In our lab, we have been working to develop biomarkers that reflect the
      common mechanisms of brain IR and AD that may be used to follow their engagement
      by experimental treatments. We present two promising biomarkers for brain IR in
      AD: insulin cascade mediators probed in extracellular vesicles (EVs) enriched for
      neuronal origin, and two-dimensional magnetic resonance spectroscopy (MRS)
      measures of brain glucose. As further evidence for a fundamental link between
      brain IR and AD, we provide a novel analysis demonstrating the close spatial
      correlation between brain expression of genes implicated in IR (using Allen Human
      Brain Atlas data) and tau and beta-amyloid pathologies. We proceed to propose the
      bold hypotheses that baseline differences in the metabolic reliance on
      glycolysis, and the expression of glucose transporters (GLUT) and insulin
      signaling genes determine the vulnerability of different brain regions to Tau
      and/or Amyloid beta (Abeta) pathology, and that IR is a critical link between
      these two pathologies that define AD. Lastly, we provide an overview of ongoing
      clinical trials that target IR as an angle to treat AD, and suggest how
      biomarkers may be used to evaluate treatment efficacy and target engagement.

PMID- 28515693
TI  - Rolipram Improves Outcome in a Rat Model of Infant Sepsis-Induced Cardiorenal
      Syndrome.
AB  - While the mortality rate associated with sepsis in children has fallen over the
      years, it still remains unacceptably high. The development of both acute cardiac
      dysfunction and acute kidney injury during severe sepsis is categorized as type 5
      cardiorenal syndrome (CRS) and is poorly understood in infants. To address this
      lack of understanding and the need for an appropriate animal model in which to
      conduct relevant preclinical studies, we developed a model of infant sepsis
      induced CRS in rat pups then evaluated the therapeutic potential of the
      phosphodiesterase (PDE) 4 inhibitor, rolipram. Rat pups at 17-18-days old were
      subjected to cecal ligation and puncture (CLP) to induce fecal polymicrobial
      sepsis. Uptake of Evans Blue dye was used to assess renal microvascular leakage.
      Intravital videomicroscopy was used to assess renal microvascular perfusion and
      oxidant generation. Glomerular filtration rate (GFR) was used to assess renal
      function. Left ventricular (LV) catheterization and echocardiography were used to
      assess cardiac function. Impairment of both cardiac and renal function developed
      rapidly following CLP, indicating type 5 CRS. Most notable were the rapid decline
      in LV diastolic function, the decline in cardiac output, renal microvascular
      failure, and the decline in GFR. A dose-response study with rolipram determined
      0.1 mg/kg, ip as the lowest most efficacious dose to protect the renal
      microcirculation. Rolipram was then evaluated using a clinically relevant delayed
      dosing paradigm (a single dose at 6 h post-CLP). With delayed dosing, rolipram
      restored the renal microcirculation and reduced microvascular leakage but did not
      reduce oxidant generation in the kidney nor restore GFR. In contrast, delayed
      dosing with rolipram restored cardiac function. Rolipram also improved 4-days
      survival. In summary, CLP in the rat pup produces a clinically relevant pediatric
      model of sepsis-induced CRS. The PDE4 inhibitor rolipram was effective in
      improving renal microvascular function and cardiac function, which improved
      mortality. These findings suggest that rolipram should be evaluated further as
      adjunctive therapy for the septic infant with CRS.

PMID- 28515694
TI  - FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?
AB  - Background and objective:FAM20A gene mutations result in enamel renal syndrome
      (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival
      fibromatosis, and impaired tooth eruption. FAM20A would control the
      phosphorylation of enamel peptides and thus enamel mineralization. Here, we
      characterized the structure and chemical composition of unerupted tooth enamel
      from ERS patients and healthy subjects. Methods: Tooth sections were analyzed by
      Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray
      Diffraction (XRD), and X-Ray Fluorescence (XRF). Results: SEM revealed that
      prisms were restricted to the inner-most enamel zones. The bulk of the
      mineralized matter covering the crown was formed by layers with varying electron
      densities organized into lamellae and micronodules. Tissue porosity progressively
      increased at the periphery, ending with loose and unfused nanonodules also
      observed in the adjoining soft tissues. Thus, the enamel layer covering the
      dentin in all ERS patients (except a limited layer of enamel at the dentino
      enamel junction) displayed an ultrastructural globular pattern similar to one
      observed in ectopic mineralization of soft tissue, notably in the gingiva of
      Fam20a knockout mice. XRD analysis confirmed the existence of alterations in
      crystallinity and composition (vs. sound enamel). XRF identified lower levels of
      calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount
      of calcium in ERS enamel, which appeared similar to dentin. Conclusion: This
      study suggests that, after an initial normal start to amelogenesis, the bulk of
      the tissue covering coronal dentin would be formed by different mechanisms based
      on nano- to micro-nodule aggregation. This evocated ectopic mineralization
      process is known to intervene in several soft tissues in FAM20A gene mutant.

PMID- 28515700
TI  - The Measurement of Aesthetic Emotion in Music.

PMID- 28515698
TI  - How Will the Mild Encephalitis Hypothesis of Schizophrenia Influence
      Stigmatization?

PMID- 28515699
TI  - Active Involvement of End Users When Developing Web-Based Mental Health
      Interventions.
AB  - BACKGROUND: Although many web-based mental health interventions are being
      released, the actual uptake by end users is limited. The marginal level of
      engagement of end users when developing these interventions is recognized as an
      important cause for uptake problems. In this paper, we offer our perceptive on
      how to improve user engagement. By doing so, we aim to stimulate a discourse on
      user involvement within the field of online mental health interventions. METHODS:
      We shortly describe three different methods (the expert-driven method,
      intervention mapping, and scrum) that were currently used to develop web-based
      health interventions. We will focus to what extent the end user was involved in
      the developmental phase, and what the additional challenges were. In the final
      paragraph, lessons learned are summarized, and recommendations provided. RESULTS:
      Every method seems to have its trade-off: if end users are highly involved,
      availability of end users and means become problematic. If end users are less
      actively involved, the product may be less appropriate for the end user. Other
      challenges to consider are the funding of the more active role of technological
      companies, and the time it takes to process the results of shorter development
      cycles. CONCLUSION: Thinking about user-centered design and carefully planning,
      the involvement of end users should become standard in the field of web-based
      (mental) health. When deciding on the level of user involvement, one should
      balance the need for input from users with the availability of resources such as
      time and funding.

PMID- 28515701
TI  - Commentary: From 'sense of number' to 'sense of magnitude' - The role of
      continuous magnitudes in numerical cognition.

PMID- 28515702
TI  - On the Tacit Aspects of Science Pedagogy in Higher Education.
AB  - In this article, we examine the concept of tacit knowledge and its implications
      for science education. We suggest that the history of scientific ideas and the
      personal nature of learning imply that higher education in scientific fields,
      wherein the generation of new knowledge, insights and understanding is paramount,
      would greatly benefit by acknowledging the irreducible role of the non-formal and
      the incidental in scientific innovation and advances.

PMID- 28515697
TI  - TRPA1 Channels Modify TRPV1-Mediated Current Responses in Dorsal Root Ganglion
      Neurons.
AB  - The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed
      in a subset of sensory neurons in the dorsal root ganglia (DRG) and trigeminal
      ganglia of experimental animals, responsible for nociception. Many researches
      have revealed that some TRPV1-positive neurons co-express the transient receptor
      potential ankyrin 1 (TRPA1) channel whose activities are closely modulated by
      TRPV1 channel. However, it is less investigated whether the activities of TRPV1
      channel are modulated by the presence of TRPA1 channel in primary sensory
      neurons. This study clarified the difference in electrophysiological responses
      induced by TRPV1 channel activation between TRPA1-positive and TRPA1-negative
      DRG. TRPV1 and TRPA1 channel activations were evoked by capsaicin (1 MUM), a
      TRPV1 agonist, and allyl isothiocyanate (AITC; 500 MUM), a TRPA1 agonist,
      respectively. Capsaicin perfusion for 15 s caused a large inward current without
      a desensitization phase at a membrane potential of -70 mV in AITC-insensitive DRG
      (current density; 29.6 +/- 5.6 pA/pF, time constant of decay; 12.8 +/- 1.8 s).
      The capsaicin-induced currents in AITC-sensitive DRG had a small current density
      (12.7 +/- 2.9 pA/pF) with a large time constant of decay (24.3 +/- 5.4 s). In
      calcium imaging with Fura-2, the peak response by capsaicin was small and
      duration reaching the peak response was long in AITC-sensitive neurons. These
      electrophysiological differences were completely eliminated by HC-030031, a TRPA1
      antagonist, in an extracellular solution or 10 mM EGTA, a Ca2+ chelator, in an
      internal solution. Capsaicin perfusion for 120 s desensitized the inward currents
      after a transient peak. The decay during capsaicin perfusion was notably slow in
      AITC-sensitive DRG; ratio of capsaicin-induced current 60 s after the treatment
      per the peak current in AITC-sensitive neurons (78 +/- 9%) was larger than that
      in AITC-insensitive neurons (48 +/- 5%). The capsaicin-induced current in the
      desensitization phase was attenuated by HC-030031 in AITC-insensitive DRG. These
      results indicate that (1) TRPV1-mediated currents in TRPA1-positive neurons
      characterize small current densities with slow decay, which is caused by TRPA1
      channel activities and intracellular Ca2+ mobilization and (2) desensitization of
      TRPV1-mediated current in TRPA1-positive neurons is apparently slow, due to
      appending TRPA1-mediated current.

PMID- 28515695
TI  - Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged
      Mice with Impaired Nrf2 Signaling.
AB  - Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling maintains the redox
      homeostasis and its activation is shown to suppress cardiac maladaptation.
      Earlier we reported that acute endurance exercise (2 days) evoked antioxidant
      cytoprotection in young WT animals but not in aged WT animals. However, the
      effect of repeated endurance exercise during biologic aging (WT) characterized by
      an inherent deterioration in Nrf2 signaling and pathological aging (pronounced
      oxidative susceptibility-Nrf2 absence) in the myocardium remains elusive. Thus,
      the purpose of our study was to determine the effect of chronic endurance
      exercise-induced cardiac adaptation in aged mice with and without Nrf2. Age
      matched WT and Nrf2-null mice (Nrf2-/-) (>22 months) were subjected to 6 weeks
      chronic endurance exercise (25 meter/min, 12% grade). The myocardial redox status
      was assessed by expression of antioxidant defense genes and proteins along with
      immunochemical detection of DMPO-radical adduct, GSH-NEM, and total
      ubiquitination. Cardiac functions were assessed by echocardiography and
      electrocardiogram. At sedentary state, loss of Nrf2 resulted in significant
      downregulation of antioxidant gene expression (Nqo1, Ho1, Gclm, Cat, and Gst
      alpha) with decreased GSH-NEM immuno-fluorescence signals. While Nrf2-/- mice
      subjected to CEE showed an either similar or more pronounced reduction in the
      transcript levels of Gclc, Nqo1, Gsr, and Gst-alpha in relation to WT
      littermates. In addition, the hearts of Nrf2-/- on CEE showed a substantial
      reduction in specific antioxidant proteins, G6PD and CAT along with decreased
      GSH, a pronounced increase in DMPO-adduct and the total ubiquitination levels.
      Further, CEE resulted in a significant upregulation of hypertrophy genes (Anf,
      Bnf, and beta-Mhc) (p < 0.05) in the Nrf2-/- hearts in relation to WT mice.
      Moreover, the aged Nrf2-/- mice exhibited a higher degree of cardiac remodeling
      in association with a significant decrease in fractional shortening, pronounced
      ST segment, and J wave elevation upon CEE compared to age-matched WT littermates.
      In conclusion, our findings indicate that while the aged WT and Nrf2 knockout
      animals both exhibit hypertrophy after CEE, the older Nrf2 knockouts showed
      ventricular remodeling coupled with profound cardiac functional abnormalities and
      diastolic dysfunction.

PMID- 28515696
TI  - The Reliability and Validity of a Four-Minute Running Time-Trial in Assessing
      [Formula: see text]max and Performance.
AB  - Introduction: Traditional graded-exercise tests to volitional exhaustion (GXTs)
      are limited by the need to establish starting workloads, stage durations, and
      step increments. Short-duration time-trials (TTs) may be easier to implement and
      more ecologically valid in terms of real-world athletic events. The purpose of
      the current study was to assess the reliability and validity of maximal oxygen
      uptake ([Formula: see text]max) and performance measured during a traditional GXT
      (STEP) and a four-minute running time-trial (RunTT). Methods: Ten recreational
      runners (age: 32 +/- 7 years; body mass: 69 +/- 10 kg) completed five STEP tests
      with a verification phase (VER) and five self-paced RunTTs on a treadmill. The
      order of the STEP/VER and RunTT trials was alternated and counter-balanced.
      Performance was measured as time to exhaustion (TTE) for STEP and VER and
      distance covered for RunTT. Results: The coefficient of variation (CV) for
      [Formula: see text]max was similar between STEP, VER, and RunTT (1.9 +/- 1.0, 2.2
      +/- 1.1, and 1.8 +/- 0.8%, respectively), but varied for performance between the
      three types of test (4.5 +/- 1.9, 9.7 +/- 3.5, and 1.8 +/- 0.7% for STEP, VER,
      and RunTT, respectively). Bland-Altman limits of agreement (bias +/- 95%) showed
      [Formula: see text]max to be 1.6 +/- 3.6 mL.kg-1.min-1 higher for STEP vs. RunTT.
      Peak HR was also significantly higher during STEP compared with RunTT (P =
      0.019). Conclusion: A four-minute running time-trial appears to provide more
      reliable performance data in comparison to an incremental test to exhaustion, but
      may underestimate [Formula: see text]max.

PMID- 28515690
TI  - Brain Renin-Angiotensin System and Microglial Polarization: Implications for
      Aging and Neurodegeneration.
AB  - Microglia can transform into proinflammatory/classically activated (M1) or anti
      inflammatory/alternatively activated (M2) phenotypes following environmental
      signals related to physiological conditions or brain lesions. An adequate
      transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is
      necessary to counteract brain damage. Several factors involved in microglial
      polarization have already been identified. However, the effects of the brain
      renin-angiotensin system (RAS) on microglial polarization are less known. It is
      well known that there is a "classical" circulating RAS; however, a second RAS
      (local or tissue RAS) has been observed in many tissues, including brain. The
      locally formed angiotensin is involved in local pathological changes of these
      tissues and modulates immune cells, which are equipped with all the components of
      the RAS. There are also recent data showing that brain RAS plays a major role in
      microglial polarization. Level of microglial NADPH-oxidase (Nox) activation is a
      major regulator of the shift between M1/proinflammatory and M2/immunoregulatory
      microglial phenotypes so that Nox activation promotes the proinflammatory and
      inhibits the immunoregulatory phenotype. Angiotensin II (Ang II), via its type 1
      receptor (AT1), is a major activator of the NADPH-oxidase complex, leading to pro
      oxidative and pro-inflammatory effects. However, these effects are counteracted
      by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and
      Angiotensin 1-7/Mas receptor (MasR) signaling. In addition, activation of
      prorenin-renin receptors may contribute to activation of the proinflammatory
      phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2
      receptor expression, which may contribute to a pro-oxidative pro-inflammatory
      state and the increase in neuron vulnerability. Several recent studies have shown
      interactions between the brain RAS and different factors involved in microglial
      polarization, such as estrogens, Rho kinase (ROCK), insulin-like growth factor-1
      (IGF-1), tumor necrosis factor alpha (TNF)-alpha, iron, peroxisome proliferator
      activated receptor gamma, and toll-like receptors (TLRs). Metabolic reprogramming
      has recently been involved in the regulation of the neuroinflammatory response.
      Interestingly, we have recently observed a mitochondrial RAS, which is altered in
      aged brains. In conclusion, dysregulation of brain RAS plays a major role in
      aging-related changes and neurodegeneration by exacerbation of oxidative stress
      (OS) and neuroinflammation, which may be attenuated by pharmacological
      manipulation of RAS components.

PMID- 28515703
TI  - Managing Contextual Complexity in an Experiential Learning Course: A Dynamic
      Systems Approach through the Identification of Turning Points in Students'
      Emotional Trajectories.
AB  - This study adopts a dynamic systems approach to investigate how individuals
      successfully manage contextual complexity. To that end, we tracked individuals'
      emotional trajectories during a challenging training course, seeking qualitative
      changes-turning points-and we tested their relationship with the perceived
      complexity of the training. The research context was a 5-day higher education
      course based on process-oriented experiential learning, and the sample consisted
      of 17 students. The students used a five-point Likert scale to rate the intensity
      of 16 emotions and the complexity of the training on 8 measurement points. Monte
      Carlo permutation tests enabled to identify 30 turning points in the 272
      emotional trajectories analyzed (17 students * 16 emotions each). 83% of the
      turning points indicated a change of pattern in the emotional trajectories that
      consisted of: (a) increasingly intense positive emotions or (b) decreasingly
      intense negative emotions. These turning points also coincided with particularly
      complex periods in the training as perceived by the participants (p = 0.003, and
      p = 0.001 respectively). The relationship between positively-trended turning
      points in the students' emotional trajectories and the complexity of the training
      may be interpreted as evidence of a successful management of the cognitive
      conflict arising from the clash between the students' prior ways of meaning
      making and the challenging demands of the training. One of the strengths of this
      study is that it provides a relatively simple procedure for identifying turning
      points in developmental trajectories, which can be applied to various
      longitudinal experiences that are very common in educational and developmental
      contexts. Additionally, the findings contribute to sustaining that the assumption
      that complex contextual demands lead unfailingly to individuals' learning is
      incomplete. Instead, it is how individuals manage complexity which may or may not
      lead to learning. Finally, this study can also be considered a first step in
      research on the developmental potential of process-oriented experiential learning
      training.

PMID- 28515704
TI  - Two Trackers Are Better than One: Information about the Co-actor's Actions and
      Performance Scores Contribute to the Collective Benefit in a Joint Visuospatial
      Task.
AB  - When humans collaborate, they often distribute task demands in order to reach a
      higher performance compared to performing the same task alone (i.e., a collective
      benefit). Here, we tested to what extent receiving information about the actions
      of a co-actor, performance scores, or receiving both types of information impacts
      the collective benefit in a collaborative multiple object tracking task. In a
      between-subject design, pairs of individuals jointly tracked a subset of target
      objects among several moving distractor objects on a computer screen for a 100
      trials. At the end of a trial, pairs received performance scores (Experiment 1),
      information about their partner's target selections (Experiment 2), or both types
      of information (Experiment 3). In all experiments, the performance of the pair
      exceeded the individual performances and the simulated performance of two
      independent individuals combined. Initially, when receiving both types of
      information (Experiment 3), pairs achieved the highest performance and divided
      task demands most efficiently compared to the other two experiments. Over time,
      performances and the ability to divide task demands for pairs receiving a single
      type of information converged with those receiving both, suggesting that pairs'
      coordination strategies become equally effective over time across experiments.
      However, pairs' performances never reached a theoretical limit of performance in
      all experiments. For distributing task demands, members of a pair predominantly
      used a left-right division of labor strategy (i.e., the leftmost targets were
      tracked by one co-actor while the rightmost targets were tracked by the other co
      actor). Overall, findings of the present study suggest that receiving information
      about actions of a co-actor, performance scores, or receiving both enables pairs
      to devise effective division of labor strategies in a collaborative visuospatial
      task. However, when pairs had both types of information available, the formation
      of division of labor strategies was facilitated, indicating that pairs benefited
      the most from having both types of information available (i.e., actions about the
      co-actor and performance scores). Findings are applicable to circumstances in
      which humans need to perform collaborative visuospatial tasks that are time
      critical and/or only allow a very limited exchange of information between co
      actors.

PMID- 28515705
TI  - Control and Effort Costs Influence the Motivational Consequences of Choice.
AB  - The act of making a choice, apart from any outcomes the choice may yield, has,
      paradoxically, been linked to both the enhancement and the detriment of intrinsic
      motivation. Research has implicated two factors in potentially mediating these
      contradictory effects: the personal control conferred by a choice and the costs
      associated with a choice. Across four experiments, utilizing a physical effort
      task disguised as a simple video game, we systematically varied costs across two
      levels of physical effort requirements (Low-Requirement, High-Requirement) and
      control over effort costs across three levels of choice (Free-Choice, Restricted
      Choice, and No-Choice) to disambiguate how these factors affect the motivational
      consequences of choosing within an effortful task. Together, our results
      indicated that, in the face of effort requirements, illusory control alone may
      not sufficiently enhance perceptions of personal control to boost intrinsic
      motivation; rather, the experience of actual control may be necessary to overcome
      effort costs and elevate performance. Additionally, we demonstrated that
      conditions of illusory control, while otherwise unmotivating, can through
      association with the experience of free-choice, be transformed to have a positive
      effect on motivation.

PMID- 28515707
TI  - Validation of Repeated Endothelial Function Measurements Using EndoPAT in Stroke.
AB  - BACKGROUND: Decreased endothelial function (EF) may be a prognostic marker for
      stroke. Measuring pharmacological effects on EF may be of interest in the
      development of personalized medicine for stroke prevention. In this study, we
      assessed the reliability of repeated EF measurements using a pulse amplitude
      tonometry technology in acute stroke patients. Similarly, reliability was tested
      in healthy subjects devoid of vascular disease to estimate reactivity and
      reliability in a younger non-stroke population. MATERIALS AND METHODS: EF was
      assessed using the EndoPAT2000 in 20 healthy volunteers (men 50%, mean age 35.85
      +/- 3.47 years) and 21 stroke patients (men 52%, mean age 66.38 +/- 2.85 years,
      and mean NIHSS 4.09 +/- 0.53) under standardized conditions. EF was measured as
      the reactive hyperemia index (RHI), logarithm of RHI (lnRHI), and Framingham RHI
      (fRHI). Measurements were separated by 1.5 and 24 h to assess same-day and day-to
      day reliability, respectively. RESULTS: Fair to moderate correlations of
      measurements [intraclass correlation coefficient (ICC)same-day 0.29 and ICCday-to
      day 0.52] were detected in healthy subjects. In stroke patients, we found
      moderate to substantial correlation of both same-day and day-to-day repeated
      measurements (ICCsame-day 0.40 and ICCday-to-day 0.62). fRHI compared with RHI
      and lnRHI showed best reliability. CONCLUSION: Repeated measurements of fRHI in
      stroke patients show moderate reliability on same-day and substantial on day-to
      day measurements. Likewise, in healthy subjects there was substantial reliability
      on day-to-day measurement, but only moderate on same-day measurements. In
      general, day-to-day correlation of repeated EF measurements was far better than
      that of same-day measurements, which ranged from poor to moderate depending on
      the specific outcome measure of EF. A possible carryover effect should be
      considered if same-day repeated testing of drug effects is applied in future
      studies.

PMID- 28515708
TI  - Disrupted Structural and Functional Networks and Their Correlation with Alertness
      in Right Temporal Lobe Epilepsy: A Graph Theory Study.
AB  - Previous studies have shown that temporal lobe epilepsy (TLE) involves abnormal
      structural or functional connectivity in specific brain areas. However, limited
      comprehensive studies have been conducted on TLE associated changes in the
      topological organization of structural and functional networks. Additionally,
      epilepsy is associated with impairment in alertness, a fundamental component of
      attention. In this study, structural networks were constructed using diffusion
      tensor imaging tractography, and functional networks were obtained from resting
      state functional MRI temporal series correlations in 20 right temporal lobe
      epilepsy (rTLE) patients and 19 healthy controls. Global network properties were
      computed by graph theoretical analysis, and correlations were assessed between
      global network properties and alertness. The results from these analyses showed
      that rTLE patients exhibit abnormal small-world attributes in structural and
      functional networks. Structural networks shifted toward more regular attributes,
      but functional networks trended toward more random attributes. After controlling
      for the influence of the disease duration, negative correlations were found
      between alertness, small-worldness, and the cluster coefficient. However,
      alertness did not correlate with either the characteristic path length or global
      efficiency in rTLE patients. Our findings show that disruptions of the
      topological construction of brain structural and functional networks as well as
      small-world property bias are associated with deficits in alertness in rTLE
      patients. These data suggest that reorganization of brain networks develops as a
      mechanism to compensate for altered structural and functional brain function
      during disease progression.

PMID- 28515710
TI  - Resistant Hypertension after Hypertensive Intracerebral Hemorrhage Is Associated
      with More Medical Interventions and Longer Hospital Stays without Affecting
      Outcome.
AB  - BACKGROUND: Hypertension (HTN) is the most common cause of spontaneous
      intracerebral hemorrhage (ICH). The aim of this study is to investigate the role
      of resistant HTN in patients with ICH. METHODS AND RESULTS: We conducted a
      retrospective study of all consecutive ICH admissions at our medical center from
      November 2013 to October 2015. The clinical features of patients with resistant
      HTN (requiring four or more antihypertensive agents to keep systolic blood
      pressure <140 mm Hg) were compared with those with responsive HTN (requiring
      three or fewer agents). Of the 152 patients with hypertensive ICH, 48 (31.6%) had
      resistant HTN. Resistant HTN was independently associated with higher body mass
      index and proteinuria. Compared to the responsive group, patients with resistant
      HTN had higher initial blood pressures and greater requirement for ventilator
      support, hematoma evacuation, hypertonic saline therapy, and nicardipine
      infusion. Resistant HTN increases length of stay (LOS) in the intensive care unit
      (ICU) (4.2 vs 2.1 days; p = 0.007) and in the hospital (11.5 vs 7.0 days; p =
      0.003). Multivariate regression analysis showed that the rate of systolic blood
      pressure >140 mm Hg and duration of nicardipine infusion were independently
      associated with LOS in the ICU. There was no significant difference in hematoma
      expansion and functional outcome at hospital discharge between the two groups.
      CONCLUSION: Resistant HTN in patients with ICH is associated with more medical
      interventions and longer LOS without effecting outcome at hospital discharge.

PMID- 28515709
TI  - Effects of 10 Hz Repetitive Transcranial Magnetic Stimulation of the Left
      Dorsolateral Prefrontal Cortex in Disorders of Consciousness.
AB  - BACKGROUND: While repetitive transcranial magnetic stimulation (rTMS) has been
      applied in treatment of patients with disorders of consciousness (DOC), a
      standardized stimulation protocol has not been proposed, and its therapeutic
      effects are inconsistently documented. OBJECTIVES: To assess the efficacy of rTMS
      in improving consciousness in patients with persistent minimally conscious state
      (MCS) or unresponsive wakefulness syndrome (UWS), previously known as vegetative
      state (VS). METHOD: A prospective single-blinded study, with selected subjects,
      was carried out. In total, 16 patients (5 MCS and 11 VS/UWS) with chronic DOC
      were included. All patients received active 10 Hz rTMS at the left dorsolateral
      prefrontal cortex (DLPFC), at one session per day, for 20 consecutive days. A
      single daily session of stimulation consisted of 1,000 pulses (10 s of 10 Hz
      trains; repeated 10 times with an inter-train interval of 60 s; and 11 min and 40
      s for total session). The main outcome measures were changes in the total score
      on the JFK Coma Recovery Scale-Revised (CRS-R) scale. Additional measures were
      the impressions of caregivers after the conclusion of the interventions, which
      were assessed using the Clinical Global Impression-Improvement (CGI-I) scale.
      RESULTS: The CRS-R scores were increased in all 5 MCS patients and 4 of 11 VS/UWS
      patients, while a significant enhancement of CRS-R scores was observed compared
      to the baseline in all participants (p = 0.007). However, the improvement was
      more notable in MCS patients (p = 0.042) than their VS/UWS counterparts (p =
      0.066). Based on the CGI-I scores, two patients improved considerably, two
      improved, six minimally improved, six experienced no change, and none
      deteriorated. Good concordance was seen between the CGI-I result and the
      increases in CRS-R scores. CONCLUSION: Treatment of 10 Hz multisession rTMS
      applied to the left DLPFC is promising for the rehabilitation of DOC patients,
      especially those in MCS. Further validation with a cohort of a larger sample size
      is required.

PMID- 28515706
TI  - Research Priorities in Limb and Task-Specific Dystonias.
AB  - Dystonia, which causes intermittent or sustained abnormal postures and movements,
      can present in a focal or a generalized manner. In the limbs, focal dystonia can
      occur in either the upper or lower limbs and may be task-specific causing
      abnormal motor performance for only a specific task, such as in writer's cramp,
      runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task
      specific and may, in some circumstances, be associated with parkinsonian
      disorders. The true prevalence of focal limb dystonia is not known and is likely
      currently underestimated, leaving a knowledge gap and an opportunity for future
      research. The pathophysiology of focal limb dystonia shares some commonalities
      with other dystonias with a loss of inhibition in the central nervous system and
      a loss of the normal regulation of plasticity, called homeostatic plasticity.
      Functional imaging studies revealed abnormalities in several anatomical networks
      that involve the cortex, basal ganglia, and cerebellum. Further studies should
      focus on distinguishing cause from effect in both physiology and imaging studies
      to permit focus on most relevant biological correlates of dystonia. There is no
      specific therapy for the treatment of limb dystonia given the variability in
      presentation, but off-label botulinum toxin therapy is often applied to focal
      limb and task-specific dystonia. Various rehabilitation techniques have been
      applied and rehabilitation interventions may improve outcomes, but small sample
      size and lack of direct comparisons between methods to evaluate comparative
      efficacy limit conclusions. Finally, non-invasive and invasive therapeutic
      modalities have been explored in small studies with design limitations that do
      not yet clearly provide direction for larger clinical trials that could support
      new clinical therapies. Given these gaps in our clinical, pathophysiologic, and
      therapeutic knowledge, we have identified priorities for future research
      including: the development of diagnostic criteria for limb dystonia, more precise
      phenotypic characterization and innovative clinical trial design that considers
      clinical heterogeneity, and limited available number of participants.

PMID- 28515711
TI  - The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible
      Mechanisms.
AB  - The impact of antidiabetic drugs on bone metabolism is drawing increasing
      attention due to the discovery of a correlation between type 2 diabetes mellitus
      (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a
      novel and promising class of drugs for T2DM, which may also have clinical
      applications in bone tissue disorders. This review examines the impact of GLP-1
      on bone metabolism, including enhancement of bone mineral density and improvement
      of bone quality. However, the precise effect of GLP-1 on fracture risk has not
      been unambiguously defined. This review also summarizes our current understanding
      of the mechanisms by which GLP-1 affects bone metabolism. GLP-1 may act on bone
      by promoting bone formation, inhibiting bone resorption, and affecting the
      coordination of the two processes. We describe molecular pathways and proteins,
      such as Wnt and calcitonin, that are associated with GLP-1 and bone tissue. The
      specific processes and related molecular mechanisms of the effects of GLP-1 on
      bone metabolism need to be further explored and clarified.

PMID- 28515713
TI  - Energy Efficiency and Productivity Enhancement of Microbial Electrosynthesis of
      Acetate.
AB  - It was hypothesized that a lack of acetogenic biomass (biocatalyst) at the
      cathode of a microbial electrosynthesis system, due to electron and nutrient
      limitations, has prevented further improvement in acetate productivity and
      efficiency. In order to increase the biomass at the cathode and thereby
      performance, a bioelectrochemical system with this acetogenic community was
      operated under galvanostatic control and continuous media flow through a
      reticulated vitreous carbon (RVC) foam cathode. The combination of galvanostatic
      control and the high surface area cathode reduced the electron limitation and the
      continuous flow overcame the nutrient limitation while avoiding the accumulation
      of products and potential inhibitors. These conditions were set with the
      intention of operating the biocathode through the production of H2. Biofilm
      growth occurred on and within the unmodified RVC foam regardless of vigorous H2
      generation on the cathode surface. A maximum volumetric rate or space time yield
      for acetate production of 0.78 g/Lcatholyte/h was achieved with 8 A/Lcatholyte
      (83.3 A/m2projected surface area of cathode) supplied to the continuous
      flow/culture bioelectrochemical reactors. The total Coulombic efficiency in H2
      and acetate ranged from approximately 80-100%, with a maximum of 35% in acetate.
      The overall energy efficiency ranged from approximately 35-42% with a maximum to
      acetate of 12%.

PMID- 28515712
TI  - Allelic Variation in Outer Membrane Protein A and Its Influence on Attachment of
      Escherichia coli to Corn Stover.
AB  - Understanding the genetic factors that govern microbe-sediment interactions in
      aquatic environments is important for water quality management and reduction of
      waterborne disease outbreaks. Although chemical properties of bacteria have been
      identified that contribute to initiation of attachment, the outer membrane
      proteins that contribute to these chemical properties still remain unclear. In
      this study we explored the attachment of 78 Escherichia coli environmental
      isolates to corn stover, a representative agricultural residue. Outer membrane
      proteome analysis led to the observation of amino acid variations, some of which
      had not been previously described, in outer membrane protein A (OmpA) at 10
      distinct locations, including each of the four extracellular loops, three of the
      eight transmembrane segments, the proline-rich linker and the dimerization
      domain. Some of the polymorphisms within loops 1, 2, and 3 were found to
      significantly co-occur. Grouping of sequences according to the outer loop
      polymorphisms revealed five distinct patterns that each occur in at least 5% of
      our isolates. The two most common patterns, I and II, are encoded by 33.3 and
      20.5% of these isolates and differ at each of the four loops. Statistically
      significant differences in attachment to corn stover were observed among isolates
      expressing different versions of OmpA and when different versions of OmpA were
      expressed in the same genetic background. Most notable was the increased corn
      stover attachment associated with a loop 3 sequence of SNFDGKN relative to the
      standard SNVYGKN sequence. These results provide further insight into the allelic
      variation of OmpA and implicate OmpA in contributing to attachment to corn
      stover.

PMID- 28515715
TI  - Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella
      cucumerina against Pseudomonas aeruginosa.
AB  - This study reported the efficacy of the metabolites of Plectosphaerella
      cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against
      Pseudomonas aeruginosa quorum sensing (QS) and QS-regulated biofilms. The minimum
      inhibitory concentration (MIC) of the ethyl acetate (EtOAc) extract from P.
      cucumerina against P. aeruginosa PAO1 was 1.25 mg mL-1. At sub-MIC
      concentrations, P. cucumerina extract (0.25-1 mg mL-1) not only inhibited biofilm
      formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without
      affecting its growth. Fluorescence and scanning electron microscope (SEM) showed
      architectural disruption of the biofilms when treated with P. cucumerina
      metabolites. Further investigation demonstrated that metabolites in P. cucumerina
      attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with
      experimentally standard samples suggested that patulin and emodin might act as
      the principal components possessing anti-biofilm and antivirulence activities.
      This is the first report of (1) the isolation of P. cucumerina from the
      phyllosphere of O. violaceus and (2) anti-biofilm, antivirulence, and biofilm
      disruption activities of this fungus. Thus, this study provides fascinating new
      pathways for screening antipathogenic agents.

PMID- 28515716
TI  - Antifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida
      albicans Yeast Forms In Vitro and In Vivo.
AB  - Vulvovaginal and invasive candidiasis are frequent conditions in immunosuppressed
      individuals caused by Candida albicans and non-albicans Candida spp. Fluconazole
      and Amphotericin B are the main drugs used to fight the infection. However,
      resistance to fluconazole and other azole antifungal drugs is an important
      clinical problem that encourages the search for new therapeutic alternatives. In
      this work, we evaluate the antifungal activity of the biphosphinic cyclopalladate
      C7a in the in vitro and in vivo model. Our results showed fungicidal activity,
      with low values of minimal inhibitory concentrations and minimum fungicidal
      concentrations, even for fluconazole and/or miconazole resistant Candida
      isolates. Fluorescence microscopy and transmission electron microscopy revealed
      that the compound was able to inhibit the formation of hyphae/pseudohyphae and,
      moreover, promoted morphological alterations in cellular organelles and
      structures, such as disruption of cell wall, apparent mitochondrial swelling,
      chromatin marginalization into the nuclei and increased numbers of electron
      lucent vacuoles. C7a significantly decreased the biofilm formation and reduced
      the viability of yeast cells in mature biofilms when tested against a virulent C.
      albicans strain. In vivo assays demonstrated a significant decrease of fungal
      burden in local (vaginal canal) and disseminated (kidneys) infection. In
      addition, we observed a significant increase in the survival of the systemically
      infected animals treated with C7a. Our results suggest C7a as a novel therapeutic
      agent for vaginal and disseminated candidiasis, and an alternative for
      conventional drug-resistant Candida.

PMID- 28515718
TI  - Fungal Diversity in Field Mold-Damaged Soybean Fruits and Pathogenicity
      Identification Based on High-Throughput rDNA Sequencing.
AB  - Continuous rain and an abnormally wet climate during harvest can easily lead to
      soybean plants being damaged by field mold (FM), which can reduce seed yield and
      quality. However, to date, the underlying pathogen and its resistance mechanism
      have remained unclear. The objective of the present study was to investigate the
      fungal diversity of various soybean varieties and to identify and confirm the FM
      pathogenic fungi. A total of 62,382 fungal ITS1 sequences clustered into 164
      operational taxonomic units (OTUs) with 97% sequence similarity; 69 taxa were
      recovered from the samples by internal transcribed spacer (ITS) region
      sequencing. The fungal community compositions differed among the tested soybeans,
      with 42 OTUs being amplified from all varieties. The quadratic relationships
      between fungal diversity and organ-specific mildew indexes were analyzed,
      confirming that mildew on soybean pods can mitigate FM damage to the seeds. In
      addition, four potentially pathogenic fungi were isolated from FM-damaged soybean
      fruits; morphological and molecular identification confirmed these fungi as
      Aspergillus flavus, A. niger, Fusarium moniliforme, and Penicillium chrysogenum.
      Further re-inoculation experiments demonstrated that F. moniliforme is dominant
      among these FM pathogenic fungi. These results lay the foundation for future
      studies on mitigating or preventing FM damage to soybean.

PMID- 28515714
TI  - New Insights into Pathogenic Vibrios Affecting Bivalves in Hatcheries: Present
      and Future Prospects.
AB  - Hatcheries constitute nowadays the only viable solution to support the husbandry
      of bivalve molluscs due to the depletion and/or overexploitation of their natural
      beds. Hatchery activities include the broodstock conditioning and spawning,
      rearing larvae and spat, and the production of microalgae to feed all stages of
      the production cycle. However, outbreaks of disease continue to be the main
      bottleneck for successful larval and spat production, most of them caused by
      different representatives of the genus Vibrio. Therefore, attention must be paid
      on preventive and management measures that allow the control of such undesirable
      bacterial populations. The present review provides an updated picture of the
      recently characterized Vibrio species associated with disease of bivalve molluscs
      during early stages of development, including the controversial taxonomic
      affiliation of some of them and relevant advances in the knowledge of their
      virulence determinants. The problematic use of antibiotics, as well as its eco
      friendly alternatives are also critically discussed.

PMID- 28515717
TI  - The Leaderless Bacteriocin Enterocin K1 Is Highly Potent against Enterococcus
      faecium: A Study on Structure, Target Spectrum and Receptor.
AB  - Enterocin K1 (EntK1), enterocin EJ97 (EntEJ97), and LsbB are three sequence
      related leaderless bacteriocins. Yet LsbB kills only lactococci while EntK1 and
      EntEJ97 target wider spectra with EntK1 being particularly active against
      Enterococcus faecium, including nosocomial multidrug resistant isolates. NMR
      study of EntK1 showed that it had a structure very similar to LsbB - both having
      an amphiphilic N-terminal alpha-helix and an unstructured C-terminus. The alpha
      helix in EntK1 is, however, about 3-4 residues longer than that of LsbB.
      Enterococcal mutants highly resistant to EntEJ97 and EntK1 were found to have
      mutations within rseP, a gene encoding a stress response membrane-bound Zn
      dependent protease. Heterologous expression of the enterococcal rseP rendered
      resistant cells of Streptococcus pneumoniae sensitive to EntK1 and EntEJ97,
      suggesting that RseP likely serves as the receptor for EntK1 and EntEJ97. It was
      also shown that the conserved proteolytic active site in E. faecalis RseP is
      partly required for EntK1 and EntEJ97 activity, since alanine substitutions of
      its conserved residues (HExxH) reduced the sensitivity of the clones to the
      bacteriocins. RseP is known to be involved in bacterial stress response. As
      expected, the growth of resistant mutants with mutations within rseP was severely
      affected when they were exposed to higher (stressing) growth temperatures, e.g.,
      at 45 degrees C, at which wild type cells still grew well. These findings allow
      us to design a hurdle strategy with a combination of the bacteriocin(s) and
      higher temperature that effectively kills bacteriocin sensitive bacteria and
      prevents the development of resistant cells.

PMID- 28515719
TI  - Production of Japanese Encephalitis Virus Antigens in Plants Using Bamboo Mosaic
      Virus-Based Vector.
AB  - Japanese encephalitis virus (JEV) is among the major threats to public health in
      Asia. For disease control and prevention, the efficient production of safe and
      effective vaccines against JEV is in urgent need. In this study, we produced a
      plant-made JEV vaccine candidate using a chimeric virus particle (CVP) strategy
      based on bamboo mosaic virus (BaMV) for epitope presentation. The chimeric virus,
      designated BJ2A, was constructed by fusing JEV envelope protein domain III
      (EDIII) at the N-terminus of BaMV coat protein, with an insertion of the foot-and
      mouth disease virus 2A peptide to facilitate the production of both unfused and
      epitope-presenting for efficient assembly of the CVP vaccine candidate. The
      strategy allowed stable maintenance of the fusion construct over long-term serial
      passages in plants. Immuno-electron microscopy examination and immunization
      assays revealed that BJ2A is able to present the EDIII epitope on the surface of
      the CVPs, which stimulated effective neutralizing antibodies against JEV
      infection in mice. This study demonstrates the efficient production of an
      effective CVP vaccine candidate against JEV in plants by the BaMV-based epitope
      presentation system.

PMID- 28515722
TI  - Corrigendum: Agro-Industrial Wastes for Production of Biosurfactant by Bacillus
      subtilis ANR 88 and Its Application in Synthesis of Silver and Gold
      Nanoparticles.
AB  - [This corrects the article on p. 492 in vol. 8, PMID: 28392783.].

PMID- 28515720
TI  - Computational Exploration of Putative LuxR Solos in Archaea and Their Functional
      Implications in Quorum Sensing.
AB  - LuxR solos are unexplored in Archaea, despite their vital role in the bacterial
      regulatory network. They assist bacteria in perceiving acyl homoserine lactones
      (AHLs) and/or non-AHLs signaling molecules for establishing intraspecies,
      interspecies, and interkingdom communication. In this study, we explored the
      potential LuxR solos of Archaea from InterPro v62.0 meta-database employing
      taxonomic, probable function, distribution, and evolutionary aspects to decipher
      their role in quorum sensing (QS). Our bioinformatics analyses showed that
      putative LuxR solos of Archaea shared few conserved domains with bacterial LuxR
      despite having less similarity within proteins. Functional characterization
      revealed their ability to bind various AHLs and/or non-AHLs signaling molecules
      that involve in QS cascades alike bacteria. Further, the phylogenetic study
      indicates that Archaeal LuxR solos (with less substitution per site) evolved
      divergently from bacteria and share distant homology along with instances of
      horizontal gene transfer. Moreover, Archaea possessing putative LuxR solos,
      exhibit the correlation between taxonomy and ecological niche despite being the
      inhabitant of diverse habitats like halophilic, thermophilic, barophilic,
      methanogenic, and chemolithotrophic. Therefore, this study would shed light in
      deciphering the role of the putative LuxR solos of Archaea to adapt varied
      habitats via multilevel communication with other organisms using QS.

PMID- 28515721
TI  - Efficacy of (+)-Lariciresinol to Control Bacterial Growth of Staphylococcus
      aureus and Escherichia coli O157:H7.
AB  - This study was undertaken to assess the antibacterial potential of a polyphenolic
      compound (+)-lariciresinol isolated from Rubia philippinensis against selected
      foodborne pathogens Staphylococcus aureus KCTC1621 and Escherichia coli O157:H7.
      (+)-Lariciresinol at the tested concentrations (250 MUg/disk) evoked a
      significant antibacterial effect as a diameter of inhibition zones (12.1-14.9 mm)
      with minimum inhibitory concentration (MIC), and minimum bactericidal
      concentration values of 125-250 and 125-250 MUg/mL, respectively. Furthermore,
      (+)-lariciresinol at MIC showed reduction in bacterial cell viabilities, efflux
      of potassium (K+) ions and release of 260 nm materials against E. coli O157:H7
      and S. aureus KCTC1621. Moreover, deteriorated cell wall morphology of E. coli
      O157:H7 and S. aureus KCTC1621 cells treated with (+)-lariciresinol at MIC
      further confirmed its inhibitory effect against the tested pathogens, suggesting
      it to be an alternative means of antimicrobials.

PMID- 28515723
TI  - Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a
      New Next-Generation Sequencing-Based Antibody Repertoire Analysis.
AB  - A diverse antibody repertoire is primarily generated by the rearrangement of V,
      D, and J genes and subsequent somatic hypermutation (SHM). Class-switch
      recombination (CSR) produces various isotypes and subclasses with different
      functional properties. Although antibody isotypes and subclasses are considered
      to be produced by both direct and sequential CSR, it is still not fully
      understood how SHMs accumulate during the process in which antibody subclasses
      are generated. Here, we developed a new next-generation sequencing (NGS)-based
      antibody repertoire analysis capable of identifying all antibody isotype and
      subclass genes and used it to examine the peripheral blood mononuclear cells of
      12 healthy individuals. Using a total of 5,480,040 sequences, we compared
      percentage frequency of variable (V), junctional (J) sequence, and a combination
      of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and
      shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes.
      The usage and diversity were similar among the immunoglobulin (Ig) subclasses.
      Clonally related sequences sharing identical V, D, J, and CDR3 amino acid
      sequences were frequently found within multiple Ig subclasses, especially between
      IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3
      genes were the least mutated among all IgG subclasses. The shared clones had
      almost the same SHM levels among Ig subclasses, while subclass-specific clones
      had different levels of SHM dependent on the genomic location. Given the
      sequential CSR, these results suggest that CSR occurs sequentially over multiple
      subclasses in the order corresponding to the genomic location of IGHCs, but CSR
      is likely to occur more quickly than SHMs accumulate within Ig genes under
      physiological conditions. NGS-based antibody repertoire analysis should provide
      critical information on how various antibodies are generated in the immune
      system.

PMID- 28515724
TI  - An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein
      Ligand-1 Collectively Control the Migration of Activated Human T-Cells.
AB  - Selectins guide the traffic of activated T-cells through the blood stream by
      mediating their tethering and rolling onto inflamed endothelium, in this way
      acting as beacons to help navigate them to sites of inflammation. Here, we
      present a comprehensive analysis of E-selectin ligands expressed on activated
      human T-cells. We identified several novel glycoproteins that function as E
      selectin ligands. Specifically, we compared the role of P-selectin glycoprotein
      ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has
      not previously been characterized as an E-selectin ligand on activated human T
      cells. We showed that CD44 acts as a functional E-selectin ligand when expressed
      on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding
      epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL).
      Furthermore, by knocking down these ligands individually or together in primary
      activated human T-cells, we demonstrated that CD44/HCELL, and not CD43,
      cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we
      demonstrated the relevance of our findings to chronic autoimmune disease, by
      showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from
      psoriasis patients, bind E-selectin.

PMID- 28515728
TI  - Corrigendum: Increased Toll-Like Receptors Activity and TLR Ligands in Patients
      with Autoimmune Thyroid Diseases.
AB  - [This corrects the article on p. 578 in vol. 7, PMID: 28018345.].

PMID- 28515729
TI  - Growth and Yield Responses of Cowpea to Inoculation and Phosphorus Fertilization
      in Different Environments.
AB  - Cowpea (Vigna unguiculata) is a major source of dietary protein and essential
      component of the cropping systems in semi-arid regions of Sub-Saharan Africa.
      However, yields are very low due to lack of improved cultivars, poor management
      practices, and limited inputs use. The objectives of this study were to assess
      the effects of rhizobia inoculant and P on nodulation, N accumulation and yield
      of two cowpea cultivars in Mozambique. Field study was conducted in three
      contrasting environments during the 2013/2014 and 2014/2015 seasons using
      randomized complete block design with four replications and four treatments.
      Treatments consisted of seed inoculation, application of 40 kg P2O5 ha-1,
      inoculation + P, and a non-inoculated control. The most probable number (MPN)
      technique was used to estimate the indigenous bradyrhizobia populations at the
      experimental sites. The rhizobia numbers at the sites varied from 5.27 * 102 to
      1.07 * 103 cells g-1 soil. Inoculation increased nodule number by 34-76% and
      doubled nodule dry weight (78 to 160 mg plant-1). P application improved
      nodulation and interacted positively with the inoculant. Inoculation, P, and
      inoculant + P increased shoot dry weight, and shoot and grain N content across
      locations but increases in number of pods plant-1, seeds pod-1, and 100-seed
      weight were not consistent among treatments across locations. Shoot N content was
      consistently high for the inoculated plants and also for the inoculated + P
      fertilized plants, whereas the non-inoculated control plants had the lowest
      tissue N content. P uptake in shoot ranged from 1.72 to 3.77 g kg-1 and was
      higher for plants that received P fertilizer alone. Inoculation and P either
      alone or in combination consistently increased cowpea grain yield across
      locations with yields ranging from 1097 kg ha-1 for the non-inoculated control to
      1674 kg ha-1 for the inoculant + P treatment. Grain protein concentration
      followed a similar trend as grain yield and ranged from 223 to 252 g kg-1 but a
      negative correlation between grain yield and protein concentration was observed.
      Inoculation increased net returns by $104-163 ha-1 over that for the control. The
      results demonstrate the potential of improving cowpea grain yield, quality and
      profitability using inoculant, although the cost-benefit for using P at the
      current fertilizer price is not attractive except when applied together with
      inoculant at low P site.

PMID- 28515725
TI  - Application of Zebrafish Models in Inflammatory Bowel Disease.
AB  - Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting
      inflammatory disease with unclear etiology. As a clinically frequent disease, it
      can affect individuals throughout their lives, with multiple complications.
      Unfortunately, traditional murine models are not efficient for the further study
      of IBD. Thus, effective and convenient animal models are needed. Zebrafish have
      been used as model organisms to investigate IBD because of their suggested highly
      genetic similarity to humans and their superiority as laboratory models. The
      zebrafish model has been used to study the composition of intestinal microbiota,
      novel genes, and therapeutic approaches. The pathogenesis of IBD is still unclear
      and many risk factors remain unidentified. In this review, we compare traditional
      murine models and zebrafish models in terms of advantages, pathogenesis, and drug
      discovery screening for IBD. We also review the progress and deficiencies of the
      zebrafish model for scientific applications.

PMID- 28515727
TI  - Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.
AB  - For decades, low- and moderate-dose radiation therapy (RT) has been shown to
      exert a beneficial therapeutic effect in a multitude of non-malignant conditions
      including painful degenerative muscoloskeletal and hyperproliferative disorders.
      Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the
      hand/foot with fibrotic nodules and fascial cords, which determine debilitating
      contractures and deformities of fingers/toes, while keloids are exuberant scar
      formations following burn damage, surgery, and trauma. Although RT has become an
      established and effective option in the management of these diseases,
      experimental studies to illustrate cellular composites and factors involved
      remain to be elucidated. More recent findings, however, indicate the involvement
      of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as
      inflammatory cells. Radiation-related molecular mechanisms affecting these target
      cells include the production of free radicals to hamper proliferative activity
      and interference with growth factors and cytokines. Moreover, an impairment of
      activated immune cells involved in both myofibroblast proliferative and
      inflammatory processes may further contribute to the clinical effects. We here
      aim at briefly describing mechanisms contributing to a modulation of
      proliferative and inflammatory processes and to summarize current concepts of
      treating hyperproliferative diseases by low and moderate doses of ionizing
      radiation.

PMID- 28515730
TI  - Analysis of MADS-Box Gene Family Reveals Conservation in Floral Organ ABCDE Model
      of Moso Bamboo (Phyllostachys edulis).
AB  - Mini chromosome maintenance 1, agamous, deficiens, and serum response factor
      (MADS)-box genes are transcription factors which play fundamental roles in flower
      development and regulation of floral organ identity. However, till date,
      identification and functions of MADS-box genes remain largely unclear in
      Phyllostachys edulis. In view of this, we performed a whole-genome survey and
      identified 34 MADS-box genes in P. edulis, and based on phylogeny, they were
      classified as MIKCC, MIKC*, Malpha, and Mbeta. The detailed analysis about gene
      structure and motifs, phylogenetic classification, comparison of gene divergence
      and duplication are provided. Interestingly, expression patterns for most genes
      were found similar to those of Arabidopsis and rice, indicating that the well
      established ABCDE model can be applied to P. edulis. Moreover, we overexpressed
      PheMADS15, an AP1-like gene, in Arabidopsis, and found that the transgenic plants
      have early flowering phenotype, suggesting that PheMADS15 might be a regulator of
      flowering transition in P. edulis. Taken together, this study provides not only
      insightful comprehension but also useful information for understanding the
      functions of MADS-box genes in P. edulis.

PMID- 28515726
TI  - Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in
      the Transmissible Tasmanian Devil Facial Tumor Disease.
AB  - Immune checkpoint molecules function as a system of checks and balances that
      enhance or inhibit immune responses to infectious agents, foreign tissues, and
      cancerous cells. Immunotherapies that target immune checkpoint molecules,
      particularly the inhibitory molecules programmed cell death 1 and cytotoxic T
      lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in
      recent years, yet little is known about these key immune signaling molecules in
      species other than primates and rodents. The Tasmanian devil facial tumor disease
      is caused by transmissible cancers that have resulted in a massive decline in the
      wild Tasmanian devil population. We have recently demonstrated that the
      inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil
      (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma
      cytokine. As this could play a role in immune evasion by tumor cells, we
      performed a thorough comparative analysis of checkpoint molecule protein
      sequences among Tasmanian devils and eight other species. We report that many of
      the key signaling motifs and ligand-binding sites in the checkpoint molecules are
      highly conserved across the estimated 162 million years of evolution since the
      last common ancestor of placental and non-placental mammals. Specifically, we
      discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM)
      inhibitory domain are completely conserved across all nine species used in our
      comparative analysis, suggesting that the function of CTLA-4 is likely conserved
      in these species. We also found that cysteine residues for intra- and
      intermolecular disulfide bonds were also highly conserved. For instance, all 20
      cysteine residues involved in disulfide bonds in the human 4-1BB molecule were
      also present in devil 4-1BB. Although many key sequences were conserved, we have
      also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and
      immunoreceptor tyrosine-based switch motifs (ITSMs) in genes and protein domains
      that have not been previously reported in any species. This checkpoint molecule
      analysis and review of salient features for each of the molecules presented here
      can serve as road map for the development of a Tasmanian devil facial tumor
      disease immunotherapy. Finally, the strategies can be used as a guide for
      veterinarians, ecologists, and other researchers willing to venture into the
      nascent field of wild immunology.

PMID- 28515731
TI  - Ectopic Expression of CDF3 Genes in Tomato Enhances Biomass Production and Yield
      under Salinity Stress Conditions.
AB  - Cycling Dof Factor (CDF) transcription factors (TFs) are involved in multiple
      processes related to plant growth and development. A member of this family, CDF3,
      has recently been linked in Arabidopsis to the regulation of primary metabolism
      and abiotic stress responses, but its role in crop production under stress is
      still unknown. In this study, we characterized tomato plants overexpressing the
      CDF3 genes from Arabidopsis and tomato and analyzed their effects on growth and
      yield under salinity, additionally gaining deeper insights into the molecular
      function of these TFs. Our results provide evidence for higher biomass production
      and yield in the 35S::AtCDF3 and 35S::SlCDF3 plants, likely due to a higher
      photosynthetic capacity resulting in increased sucrose availability.
      Transcriptome analysis revealed that CDF3 genes regulate a set of genes involved
      in redox homeostasis, photosynthesis performance and primary metabolism that lead
      to enhanced biomass production. Consistently, metabolomic profiling revealed that
      CDF3 evokes changes in the primary metabolism triggering enhanced nitrogen
      assimilation, and disclosed that the amount of some protective metabolites
      including sucrose, GABA and asparagine were higher in vegetative tissues of CDF3
      overexpressing plants. Altogether these changes improved performance of
      35S::AtCDF3 and 35S::SlCDF3 plants under salinity conditions. Moreover, the
      overexpression of CDF3 genes modified organic acid and sugar content in fruits,
      improving variables related to flavor perception and fruit quality. Overall, our
      results associate the CDF3 TF with a role in the control of growth and C/N
      metabolism, and highlight that overexpression of CDF3 genes can substantially
      improve plant yield.

PMID- 28515732
TI  - Osmotic Stress Induced Cell Death in Wheat Is Alleviated by Tauroursodeoxycholic
      Acid and Involves Endoplasmic Reticulum Stress-Related Gene Expression.
AB  - Although, tauroursodeoxycholic acid (TUDCA) has been widely studied in mammalian
      cells because of its role in inhibiting apoptosis, its effects on plants remain
      almost unknown, especially in the case of crops such as wheat. In this study, we
      conducted a series of experiments to explore the effects and mechanisms of action
      of TUDCA on wheat growth and cell death induced by osmotic stress. Our results
      show that TUDCA: (1) ameliorates the impact of osmotic stress on wheat height,
      fresh weight, and water content; (2) alleviates the decrease in chlorophyll
      content as well as membrane damage caused by osmotic stress; (3) decreases the
      accumulation of reactive oxygen species (ROS) by increasing the activity of
      antioxidant enzymes under osmotic stress; and (4) to some extent alleviates
      osmotic stress-induced cell death probably by regulating endoplasmic reticulum
      (ER) stress-related gene expression, for example expression of the basic leucine
      zipper genes bZIP60B and bZIP60D, the binding proteins BiP1 and BiP2, the protein
      disulfide isomerase PDIL8-1, and the glucose-regulated protein GRP94. We also
      propose a model that illustrates how TUDCA alleviates osmotic stress-related
      wheat cell death, which provides an important theoretical basis for improving
      plant stress adaptation and elucidates the mechanisms of ER stress-related plant
      osmotic stress resistance.

PMID- 28515734
TI  - Plant Growth under Natural Light Conditions Provides Highly Flexible Short-Term
      Acclimation Properties toward High Light Stress.
AB  - Efficient acclimation to different growth light intensities is essential for
      plant fitness. So far, most studies on light acclimation have been conducted with
      plants grown under different constant light regimes, but more recent work
      indicated that acclimation to fluctuating light or field conditions may result in
      different physiological properties of plants. Thale cress (Arabidopsis thaliana)
      was grown under three different constant light intensities (LL: 25 MUmol photons
      m-2 s-1; NL: 100 MUmol photons m-2 s-1; HL: 500 MUmol photons m-2 s-1) and under
      natural fluctuating light (NatL) conditions. We performed a thorough
      characterization of the morphological, physiological, and biochemical properties
      focusing on photo-protective mechanisms. Our analyses corroborated the known
      properties of LL, NL, and HL plants. NatL plants, however, were found to combine
      characteristics of both LL and HL grown plants, leading to efficient and unique
      light utilization capacities. Strikingly, the high energy dissipation capacity of
      NatL plants correlated with increased dynamics of thylakoid membrane
      reorganization upon short-term acclimation to excess light. We conclude that the
      thylakoid membrane organization and particularly the light-dependent and
      reversible unstacking of grana membranes likely represent key factors that
      provide the basis for the high acclimation capacity of NatL grown plants to
      rapidly changing light intensities.

PMID- 28515733
TI  - Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in
      Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different
      Plant Organs.
AB  - Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in
      traditional Chinese medicine, is widely distributed in South China, especially in
      Fujian. Recent studies about B. cusia mainly focus on its chemical composition
      and pharmacological effects, but further analysis of the plant's gene functions
      and expression is required to better understand the synthesis of its effective
      compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a
      powerful method for gene expression analysis. It is necessary to select a
      suitable reference gene for expression normalization to ensure the accuracy of RT
      qPCR results. Ten candidate reference genes were selected from the transcriptome
      datasets of B. cusia in this study, and the expression stability was assessed
      across 60 samples representing different tissues and organs under various
      conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic
      acid methyl ester and abscisic acid), and in different plant organs. By employing
      different algorithms, such as geNorm, NormFinder, and BestKeeper, which are
      complementary approaches based on different statistical procedures, 18S rRNA was
      found to be the most stable gene under UV irradiation and hormonal stimuli,
      whereas ubiquitin-conjugating enzyme E2 was the best suitable gene for different
      plant organs. This novel study aimed to screen for suitable reference genes and
      corresponding primer pairs specifically designed for gene expression studies in
      B. cusia, in particular for RT-qPCR analyses.

PMID- 28515736
TI  - Expression of Key Structural Genes of the Phenylpropanoid Pathway Associated with
      Catechin Epimerization in Tea Cultivars.
AB  - Catechin epimerization is an important factor affecting tea catechin compositions
      and thereby tea quality. However, a lack of tea germplasms with high non
      epicatechins limits relative research. Here, a tea cultivar Y510 with high non
      epicatechins was firstly reported and used for catechin and RNA sequencing (RNA
      Seq) analysis. Results showed that the (-)-gallocatechin gallate and (+)-catechin
      (C) contents in Y510 were at least 136 and 6 times higher than those in
      Fudingdabaicha and 0306I, but the epicatechins (-)-epigallocatechin and (-)
      epicatechin (EC) were significantly lower. Eleven unigenes potentially involved
      in catechin epimerization were identified by RNA-Seq analysis. Based on a
      combination of catechin and gene expression analysis, it was hypothesized that
      two anthocyanidin reductase genes (CsANR1, CsANR2) and an anthocyanidin synthase
      gene (CsANS) are the key genes affecting catechin epimerization in tea. Non
      epicatechin formations were hypothesized to be mainly influenced by the
      expression ratio of CsANR2 to CsANR1 and the expression of CsANS. Overexpression
      of CsANS in an Arabidopsis mutant tds4-2 led to a significant increase of EC
      accumulation in seeds, revealing CsANS is important for catechin epimerization.
      These results shed new light on breeding tea cultivars with special catechin
      compositions.

PMID- 28515737
TI  - The Complete Plastome Sequences of Four Orchid Species: Insights into the
      Evolution of the Orchidaceae and the Utility of Plastomic Mutational Hotspots.
AB  - Orchidaceae (orchids) is the largest family in the monocots, including about
      25,000 species in 880 genera and five subfamilies. Many orchids are highly valued
      for their beautiful and long-lasting flowers. However, the phylogenetic
      relationships among the five orchid subfamilies remain unresolved. The major
      dispute centers on whether the three one-stamened subfamilies, Epidendroideae,
      Orchidoideae, and Vanilloideae, are monophyletic or paraphyletic. Moreover,
      structural changes in the plastid genome (plastome) and the effective genetic
      loci at the species-level phylogenetics of orchids have rarely been documented.
      In this study, we compared 53 orchid plastomes, including four newly sequenced
      ones, that represent four remote genera: Dendrobium, Goodyera, Paphiopedilum, and
      Vanilla. These differ from one another not only in their lengths of inverted
      repeats and small single copy regions but also in their retention of ndh genes.
      Comparative analyses of the plastomes revealed that the expansion of inverted
      repeats in Paphiopedilum and Vanilla is associated with a loss of ndh genes. In
      orchid plastomes, mutational hotspots are genus specific. After having carefully
      examined the data, we propose that the three loci 5'trnK-rps16, trnS-trnG, and
      rps16-trnQ might be powerful markers for genera within Epidendroideae, and clpP
      psbB and rps16-trnQ might be markers for genera within Cypripedioideae. After
      analyses of a partitioned dataset, we found that our plastid phylogenomic trees
      were congruent in a topology where two one-stamened subfamilies (i.e.,
      Epidendroideae and Orchidoideae) were sisters to a multi-stamened subfamily
      (i.e., Cypripedioideae) rather than to the other one-stamened subfamily
      (Vanilloideae), suggesting that the living one-stamened orchids are paraphyletic.

PMID- 28515735
TI  - Time-Course Transcriptome Analysis of Compatible and Incompatible Pollen-Stigma
      Interactions in Brassica napus L.
AB  - Brassica species exhibit both compatible and incompatible pollen-stigma
      interactions, however, the underlying molecular mechanisms remain largely
      unknown. Here, RNA-seq technology was applied in a comprehensive time-course
      experiment (2, 5, 10, 20, and 30 min) to explore gene expression during
      compatible/incompatible pollen-stigma interactions in stigma. Moderate changes of
      gene expression were observed both in compatible pollination (PC) and
      incompatible pollination (PI) within 10 min, whereas drastic changes showed up by
      30 min, especially in PI. Stage specific DEGs [Differentially Expressed Gene(s)]
      were identified, and signaling pathways such as stress response, defense
      response, cell wall modification and others were found to be over-represented. In
      addition, enriched genes in all samples were analyzed as well, 293 most highly
      expressed genes were identified and annotated. Gene Ontology and metabolic
      pathway analysis revealed 10 most highly expressed genes and 37 activated
      metabolic pathways. According to the data, downstream components were activated
      in signaling pathways of both compatible and incompatible responses, and
      incompatible response had more complicated signal transduction networks. This
      study provides more detailed molecular information at different time points after
      compatible and incompatible pollination, deepening our knowledge about pollen
      stigma interactions.

PMID- 28515667
TI  - Measurement of azimuthal correlations of D mesons with charged particles in pp
      collisions at [Formula: see text] TeV and p-Pb collisions at [Formula: see text]
      TeV.
AB  - The azimuthal correlations of D mesons with charged particles were measured with
      the ALICE apparatus in pp collisions at [Formula: see text] and p-Pb collisions
      at [Formula: see text] at the Large Hadron Collider. [Formula: see text],
      [Formula: see text], and [Formula: see text] mesons and their charge conjugates
      with transverse momentum [Formula: see text] and rapidity in the nucleon-nucleon
      centre-of-mass system [Formula: see text] (pp collisions) and [Formula: see text]
      (p-Pb collisions) were correlated to charged particles with [Formula: see text].
      The yield of charged particles in the correlation peak induced by the jet
      containing the D meson and the peak width are compatible within uncertainties in
      the two collision systems. The data are described within uncertainties by Monte
      Carlo simulations based on PYTHIA, POWHEG, and EPOS 3 event generators.

PMID- 28515739
TI  - Patterns of Inter-Chromosomal Gene Conversion on the Male-Specific Region of the
      Human Y Chromosome.
AB  - The male-specific region of the human Y chromosome (MSY) is characterized by the
      lack of meiotic recombination and it has long been considered an evolutionary
      independent region of the human genome. In recent years, however, the idea that
      human MSY did not have an independent evolutionary history begun to emerge with
      the discovery that inter-chromosomal gene conversion (ICGC) can modulate the
      genetic diversity of some portions of this genomic region. Despite the study of
      the dynamics of this molecular mechanism in humans is still in its infancy, some
      peculiar features and consequences of it can be summarized. The main effect of
      ICGC is to increase the allelic diversity of MSY by generating a significant
      excess of clustered single nucleotide polymorphisms (SNPs) (defined as groups of
      two or more SNPs occurring in close proximity and on the same branch of the Y
      phylogeny). On the human MSY, 13 inter-chromosomal gene conversion hotspots
      (GCHs) have been identified so far, involving donor sequences mainly from the X
      chromosome and, to a lesser extent, from autosomes. Most of the GCHs are
      evolutionary conserved and overlap with regions involved in aberrant X-Y crossing
      over. This review mainly focuses on the dynamics and the current knowledge
      concerning the recombinational landscape of the human MSY in the form of ICGC, on
      how this molecular mechanism may influence the evolution of the MSY, and on how
      it could affect the information enclosed within a genomic region which, until
      recently, appeared to be an evolutionary independent unit.

PMID- 28515738
TI  - Chloroplast ATP Synthase Modulation of the Thylakoid Proton Motive Force:
      Implications for Photosystem I and Photosystem II Photoprotection.
AB  - In wild type plants, decreasing CO2 lowers the activity of the chloroplast ATP
      synthase, slowing proton efflux from the thylakoid lumen resulting in buildup of
      thylakoid proton motive force (pmf). The resulting acidification of the lumen
      regulates both light harvesting, via the qE mechanism, and photosynthetic
      electron transfer through the cytochrome b6f complex. Here, we show that the cfq
      mutant of Arabidopsis, harboring single point mutation in its gamma-subunit of
      the chloroplast ATP synthase, increases the specific activity of the ATP synthase
      and disables its down-regulation under low CO2. The increased thylakoid proton
      conductivity (gH+) in cfq results in decreased pmf and lumen acidification,
      preventing full activation of qE and more rapid electron transfer through the b6f
      complex, particularly under low CO2 and fluctuating light. These conditions favor
      the accumulation of electrons on the acceptor side of PSI, and result in severe
      loss of PSI activity. Comparing the current results with previous work on the
      pgr5 mutant suggests a general mechanism where increased PSI photodamage in both
      mutants is caused by loss of pmf, rather than inhibition of CEF per se. Overall,
      our results support a critical role for ATP synthase regulation in maintaining
      photosynthetic control of electron transfer to prevent photodamage.

PMID- 28515741
TI  - Respiratory functional status after conventional and minimally invasive aortic
      valve replacement surgery - a propensity score analysis.
AB  - INTRODUCTION: Reports describing respiratory function of patients after
      conventional or minimally invasive cardiac surgery are infrequent. AIM: To
      compare pulmonary functional status after conventional (AVR) and after minimally
      invasive, through right anterior minithoracotomy, aortic valve replacement (RT
      AVR). MATERIAL AND METHODS: This was an observational analysis of 212 patients
      scheduled for RT-AVR and 212 for AVR between January 2011 and December 2014
      selected using propensity score matching. Respiratory function based on
      spirometry examinations is presented. RESULTS: Hospital mortality was 1.4% in RT
      AVR and 1.9% in AVR (p = 0.777). Predicted mortality (EuroSCORE II) was 3.2 +/
      1.1% in RT-AVR and 3.1 +/-1.6% in AVR (p = 0.298). Mechanical ventilation time in
      intensive care unit (ICU) was 7.3 +/-3.9 h for RT-AVR and 9.6 +/-5.5 h for AVR
      patients (p < 0.001). Seven days and 1 month after surgery, the reduction of
      spirometry functional tests was greater in the AVR group than in the RT-AVR group
      (p < 0.001). Three months after surgery, all spirometry parameters were still
      reduced and had not returned to preoperative values in both RT-AVR and AVR
      groups. However, the difference in spirometry values was no longer statistically
      significant between RT-AVR and AVR groups. Presence of chronic obstructive
      pulmonary disease and conventional AVR surgical technique were associated with
      lower values of spirometry parameters after surgery in linear median regression.
      CONCLUSIONS: Respiratory function based on spirometry examinations was less
      impaired after minimally invasive RT-AVR surgery in comparison to conventional
      AVR surgery through median sternotomy.

PMID- 28515742
TI  - The use of intraoperative epiaortic ultrasonography in monitoring patients over
      75 years old treated with aortic valve replacement.
AB  - INTRODUCTION: Epiaortic ultrasound scanning (EAS) extended the use of ultrasound
      to the intraoperative diagnosis of aortic pathology. Surgical palpation of the
      ascending aorta underestimates the presence and severity of atherosclerotic
      plaques. Epiaortic ultrasound scanning has been used as an adjunct to
      transesophageal echocardiography (TEE) or as a primary direct diagnostic tool for
      imaging the ascending aorta as well as the aortic arch, which gained prominence
      as part of a multipronged intraoperative strategy to reduce atherosclerotic
      emboli. AIM: To compare the epiaortic examination with transthoracic and
      transesophageal echo (transthoracic echocardiography (TTE) and TEE), X-ray,
      surgical intraoperative palpation, and postoperative neurological status.
      MATERIAL AND METHODS: The analyzed group consisted of 35 patients (mean age: 81.3
      years) treated with aortic valve replacement (AVR), either alone (60%) or
      combined with coronary artery bypass grafting (CABG; 22.8%) or aortic aneurysm
      replacement (11.42%). In 2 patients, only CABG was performed because
      intraoperatively reevaluated strategy. Thierteen patients have got a history of
      diabetes, 10 chronic renal failure and 3 of cerebral stroke. RESULTS: In more
      than 80% of patients, positive EAS results had an influence on the choice of
      aortic clamping site and in 50% of patients on the site of cannulation. Female
      sex, peripheral vascular disease, history of previous stroke, and calcifications
      in the ascending aorta in TTE have significant predictive value for recognizing
      atherosclerotic changes in EAS and the risk of postoperative neurological
      complications in octogenarians treated with AVR. CONCLUSIONS: Epiaortic
      ultrasound scanning imaging is superior to TTE and manual palpation in the
      detection and localization of ascending atherosclerosis. This technique should be
      introduced as a standard perioperative examination in older patients at risk of
      neurological complications.

PMID- 28515740
TI  - Left atrial appendage occlusion procedures.

PMID- 28515744
TI  - Mycobacterium chimaera - a new threat for cardiac surgical patients?
AB  - An outbreak of invasive Mycobacterium chimaera infections associated with "heater
      cooler" devices in patients treated with cardiac surgery has been described
      worldwide. The authors summarize the current state of knowledge regarding the
      epidemiology, diagnostics, treatment, and prevention of Mycobacterium chimaera
      infections in patients after cardiothoracic surgery.

PMID- 28515745
TI  - New aspects in the diagnosis and treatment of primary spontaneous pneumothorax.
AB  - This paper provides a recapitulation of the position of the British Thoracic
      Society and the American College of Chest Physicians based on a review of the
      literature concerning the current methods of diagnosing and treating primary
      spontaneous pneumothorax (PSP). The previously developed guidelines were re
      evaluated in 2015 by a task force of the European Respiratory Society (ERS). They
      are intended to be used by surgeons as well as emergency and pulmonary ward
      physicians, and they apply largely to emergency procedures. In recent years, the
      effectiveness of minimally invasive methods (punctures, drainage) in combination
      with talc pleurodesis for the initial therapy of PSP has been recognized. The
      efficacy of thoracoscopy (VATS) for the treatment of this disease has been proven
      by the development of minimally invasive surgical techniques in thoracic surgery.
      This paper also discusses the efficacy of the surgical methods available.

PMID- 28515743
TI  - Acute-phase proteins and oxidative stress in patients undergoing coronary artery
      bypass graft: comparison of cardioplegia strategy.
AB  - INTRODUCTION: Several strategies are still being introduced to cardiac surgery
      techniques to reduce the signs of the inflammatory response and oxidative stress.
      Many efforts have been made to develop the best possible method for myocardial
      protection. AIM: To assess the effect of the cardioplegia strategy on the
      systemic inflammatory response and oxidative stress. MATERIAL AND METHODS: A
      group of 238 consecutive, elective on-pump coronary artery bypass graft patients
      (CABG; 183 men, aged 64.6 +/-8.1 years) were prospectively studied. Patients were
      enrolled in two groups: with warm blood cardioplegia (n = 124) and with cold
      crystalloid cardioplegia (n = 114). In each group, pre- and postoperative levels
      of plasma C-reactive protein, fibrinogen, interleukin 6 and 8-iso-prostaglandin
      F2alpha (8-iso-PGF2alpha) were measured. RESULTS: All studied markers
      significantly increased 18-36 h following CABG and then decreased in 5-7
      postoperative days but remained above baseline levels. No differences in terms of
      studied markers and clinical outcomes were noted for the different types of
      cardioplegia. Regression analysis showed a significant correlation between
      preoperative level of oxidative stress measured by 8-iso-PGF2alpha and
      postoperative myocardial infarction as well as in-hospital cardiovascular death
      (p = 0.047 and p = 0.041 respectively). CONCLUSIONS: This study extends previous
      reports by showing that the type of cardioplegia does not affect the systemic
      inflammatory response or oxidative stress, which are associated with the CABG
      procedure. It might be speculated that preoperative screening of oxidative stress
      could be helpful in identifying patients at increased risk of an unfavorable
      course after CABG.

PMID- 28515746
TI  - Veno-arterial extracorporeal membrane oxygenation as cardiogenic shock therapy
      support in adult patients after heart surgery.
AB  - INTRODUCTION: The authors present their personal experience in qualifying and
      treating adult patients using veno-arterial (VA) extracorporeal membrane
      oxygenation (ECMO) in postcardiotomy cardiogenic shock. AIM: The aim of this
      study was to analyze the results of VA ECMO in patients with postcardiotomy
      cardiogenic shock. An analysis of the risk factors of postoperative mortality was
      also performed. MATERIAL AND METHODS: We analyzed the perioperative results of
      survivors and non-survivors of treatment using VA ECMO. We compared the number of
      days on VA ECMO therapy, types of cardiac surgical procedures, and the frequency
      of VA ECMO complications such as coagulation disorders, lower limb ischemia,
      cardiac tamponade, and renal replacement therapy. RESULTS: There were 27 patients
      treated with VA ECMO during the study period. The mean patient age was 45 +/-16
      years. The hospital mortality rate of patients treated with VA ECMO therapy was
      70% (19/27). There were no significant differences between the groups of
      survivors and non-survivors regarding age, gender, admission type and coexisting
      diseases. Type of cardiac surgical procedure had no influence on mortality or
      complications of therapy using VA ECMO. CONCLUSIONS: The VA ECMO can be an
      effective form of therapy in some patients in postcardiotomy cardiogenic shock.

PMID- 28515748
TI  - Effects of propolis on warfarin efficacy.
AB  - INTRODUCTION: Warfarin is commonly used to avoid thromboembolism, predominantly
      for cardiovascular pathologies. However, the consumption of several herbal
      products is not permitted during its use due to the associated interactions.
      Propolis is a popular phytotherapy product made by honey bees. The use of
      propolis has been dramatically increasing in recent times. AIM: To evaluate the
      possible interactions between propolis and warfarin in a mouse model with
      determination of the international normalized ratio (INR) values. MATERIAL AND
      METHODS: CD-1 mice were employed in the experimental model. The mice were
      warfarinized, and propolis was administered simultaneously. The INR values were
      obtained. All animals were sacrificed at the end of the study. RESULTS: The
      baseline INR value was 0.8 +/-0.1. After 72 h, the INR value increased as
      expected. The INR value was 7.28 +/-1.08 in the control group and 5.8 +/-2.88 in
      the propolis group. At the end of the study, the INR value was 1.3 +/-0.37.
      Propolis interacted with warfarin and caused a decrease in the INR value.
      CONCLUSIONS: Propolis interactions, especially with warfarin, should be kept in
      mind and further studied. Healthcare specialists should be aware of this possible
      interaction between warfarin and propolis and inform patients about it.

PMID- 28515747
TI  - Revascularization in ischemic heart failure with reduced left ventricular
      ejection fraction. The impact of complete revascularization.
AB  - Heart failure is a growing problem worldwide, with coronary artery disease being
      the underlying cause of over two-thirds of cases. Revascularization in this group
      of patients may potentially inhibit the progressive damage to the myocardium and
      lead to improved outcomes, but data in this area are scarce. This article
      emphasizes the role of qualification for revascularization and selection of
      method (percutaneous coronary intervention vs. coronary artery bypass grafting)
      and subsequently focuses on the issue of completeness of revascularization in
      this group of patients.

PMID- 28515751
TI  - Malignant triton tumor of the lung, infiltrating the left atrium and left
      ventricle, with metastasis to the small intestine.
AB  - Malignant triton tumors are a rare subtype of malignant peripheral nerve sheath
      tumors showing rhabdomyosarcomatous differentiation. We report the case of a 33
      year-old patient who underwent an excision of such a tumor by thoracic and
      cardiac surgery. He was reoperated on 1 month later because of a tumor of the
      small intestine and received adjuvant radiation.

PMID- 28515749
TI  - Thromboembolic complications after an ankle joint open fracture in a patient with
      a history of deep vein thrombosis in the lower limbs.
AB  - A 55-year-old patient was admitted to the Department of Orthopedics due to an
      open fracture in the right ankle joint. On the seventh day of hospitalization the
      patient experienced a transient ischemic attack. During the next day, dyspnea,
      chest pain and a 'rider' type pulmonary embolism in the pulmonary trunk occluding
      both pulmonary arteries and its branches were diagnosed. The patient was
      transferred to the Department of Cardiac Surgery. He underwent pulmonary
      embolectomy for massive pulmonary, right and left atrial embolism, and left
      ventricular embolism. ASD II was closed during this procedure. Ultrasonography
      with Doppler was performed 6 days after the surgery and revealed deep vein
      thrombosis, so the patient was transferred to the Department of Vascular Surgery
      for temporary inferior vena cava filter placement at the time of orthopedic
      surgery. The next day after implantation of the filter, the lower limb was
      operated on, and 14 days after orthopedic surgery, the vena cava filter was
      removed.

PMID- 28515750
TI  - Hiatal hernia after esophagectomy - a report of two cases.
AB  - Postoperative hiatal hernia after esophagectomy occurs with a frequency of 0.4
      6%, and the local conditions following esophagectomy promote its occurrence. In
      the material presented here, hiatal hernia in the form of displacement of the
      colon to the mediastinum was established in 0.78% (2/256) of all performed
      esophagectomies. Both cases were reoperated successfully.

PMID- 28515752
TI  - Extended resection of the trachea in a patient with cicatricial tracheal stenosis
      after tracheostomy complicated with esophageal-tracheal fistula and extensive
      defect of the frontal tracheal wall.
AB  - We present a case of one-stage radical surgical treatment of a 24-year-old female
      patient with cicatricial granulating tracheal stenosis after tracheostomy
      complicated by esophageal-tracheal fistula and an extensive defect of the
      anterior wall of the trachea after numerous unsuccessful attempts to correct the
      narrowing of the trachea and eliminate the fistula by endoscopic and open
      surgical techniques. The patient underwent extended tracheal resection with end
      to-end anastomosis with liquidation of the esophageal-tracheal fistula and
      elimination of the defect of the anterior wall of the trachea by cervical access.

PMID- 28515754
TI  - Traumatic tension pneumopericardium and amputation of the left main bronchus.
AB  - A 27-year-old woman sustained a blunt chest trauma after a car accident. Computed
      tomography revealed tension pneumopericardium, bilateral pneumothorax, and a
      suspected rupture of the left main bronchus. Emergent pericardial needle
      aspiration was successfully performed. Bronchial amputation was confirmed by
      bronchofiberoscopy. Despite total detachment of the distal part of the bronchial
      tree, the ventilation of the left lung was maintained without air leakage by use
      of pleural drains. Bronchial obturation resulted from the injury, and was
      effectively treated by bronchoscopic sputum suction at the distal end of the
      bronchus. Finally, the patient underwent a left thoracotomy with an end-to-end
      bronchial anastomosis. The patient was discharged home on the 32nd day after the
      trauma, and no complications were recorded during a 3-month follow-up period.

PMID- 28515755
TI  - Common origin of all three coronary arteries from the right sinus of Valsalva -
      first case study accompanied by mitral valve prolapse and vein anomaly, second
      case study followed by successful percutaneous coronary intervention of right
      coronary artery stenosis.
AB  - Congenital anomalies of the coronary arteries can be divided into two broad
      categories: those that alter myocardial perfusion and those that do not. In
      coronary anomalies not altering myocardial perfusion, the coronary arteries
      originate from the aorta, but their origins are in unusual positions. Although
      myocardial perfusion is normal, the angiographer may have trouble locating them.
      Patients with an anomalous left main coronary artery arising from the right sinus
      of Valsalva are presented. The diagnosis was made by coronary angiography,
      transesophageal echocardiography and multislice computed tomography (MSCT). We
      present two cases: the first patient with coronary abnormalities had accompanying
      venous anomaly of lower extremities and mitral valve prolapse as well. The second
      patient had a history of anterior wall myocardial infarction and angioplasty with
      stent implantation. The extraordinary passage of the left coronary artery between
      the pulmonary trunk and sternum, undetectable in coronarography, was discovered
      due to MSCT.

PMID- 28515756
TI  - Left main bronchus separation after blunt trauma.
AB  - Tracheobronchial damage is very rare in clinical practice and represents no more
      than 1% of all injuries caused by blunt trauma. Nearly 80% of patients die before
      reaching the hospital. Most ruptures are observed in the right main bronchus and
      are located within 2 cm of the carina trachea. The highest mortality rate applies
      to patients with bilateral bronchial injuries. Nonspecific symptoms, additionally
      masked by complaints regarding other damaged organs, delay the diagnosis and
      surgical treatment. The aim of this article is to present one particular clinical
      case and to discuss it in conjunction with a literature review.

PMID- 28515753
TI  - Traumatic pneumatocele in an 11-year-old boy - report of a rare case and review
      of the literature.
AB  - The authors present a case of a pneumatocele associated with blunt trauma in a
      child. An 11-year-old boy was admitted to the emergency department after he was
      knocked over and his chest was trapped under a soccer goal. Chest computed
      tomography (CT) revealed several cavities in the lobes of both lungs. The CT of
      the abdomen revealed traumatic laceration of the liver. The patient was treated
      conservatively. His condition was stable and subsequently improved. He was
      discharged 19 days later. After nine months, a chest radiograph showed complete
      resolution of the pneumatocele, and abdominal ultrasound demonstrated complete
      resolution of the liver hematoma. A traumatic pneumatocele is a benign lesion
      resulting from blunt chest trauma, usually in children and young adults, which
      typically requires only conservative treatment. The CT scanning is the most
      sensitive method for the detection of traumatic pneumatoceles. All emergency
      physicians should be familiar with the diagnosis and management of this
      condition, to avoid unnecessary invasive procedures.

PMID- 28515757
TI  - Emergency HeartWare Ventricular Assist Device (HVAD) exchange due to pump
      thrombosis using minimally invasive technique.
AB  - Left ventricular assist device (LVAD) thrombosis remains a dreadful complication
      of mechanical circulatory support, with an incidence of 8-12% depending on the
      pump type and patient's comorbidities. Fibrinolysis may be considered early in
      pump thrombosis, but when contraindicated a pump exchange remains the only
      alternative. This short report documents an emergency LVAD exchange in a 55-year
      old man who underwent LVAD (HeartWare Inc) implantation in 2013 as a bridge to
      transplantation. Four months after the initial surgery, he suffered from a
      hemorrhagic stroke despite properly managed anticoagulation. On February 17th,
      2017 he was re-admitted with LVAD pump thrombosis. As fibrinolysis was
      contraindicated, an emergency pump exchange was performed via a limited thoracic
      incision in order to minimize surgical trauma, reduce intraoperative
      complications and facilitate immediate post-operative recovery. This report
      documents the very first LVAD pump exchange as well as the first one performed
      via a minimally invasive approach in Poland.

PMID- 28515758
TI  - Medical robots in cardiac surgery - application and perspectives.
AB  - Medical robots offer new standards and opportunities for treatment. This paper
      presents a review of the literature and market information on the current
      situation and future perspectives for the applications of robots in cardiac
      surgery. Currently in the United States, only 10% of thoracic surgical procedures
      are conducted using robots, while globally this value remains below 1%. Cardiac
      and thoracic surgeons use robotic surgical systems increasingly often. The goal
      is to perform more than one hundred thousand minimally invasive robotic surgical
      procedures every year. A surgical robot can be used by surgical teams on a
      rotational basis. The market of surgical robots used for cardiovascular and lung
      surgery was worth 72.2 million dollars in 2014 and is anticipated to reach 2.2
      billion dollars by 2021. The analysis shows that Poland should have more than 30
      surgical robots. Moreover, Polish medical teams are ready for the introduction of
      several robots into the field of cardiac surgery. We hope that this market will
      accommodate the Polish Robin Heart robots as well.

PMID- 28515759
TI  - Department of Pediatric Cardiac Surgery in Gdansk in its new location - previous
      activity and perspectives for development.
AB  - The Department of Pediatric Cardiac Surgery in Gdansk is the only pediatric
      cardiac surgery center in northern Poland providing comprehensive treatment to
      children with congenital heart defects. The Department of Pediatric Cardiac
      Surgery in Gdansk currently offers a full spectrum of advanced procedures of
      modern cardiac surgery and interventional cardiology dedicated to patients from
      infancy to adolescence. January 19, 2016 marked the official opening of its new
      location.

PMID- 28515760
TI  - Retraction notice.
AB  - [This retracts the article DOI: 10.5114/kitp.2016.61054.].

PMID- 28515762
TI  - Biochemical and histopathological effects of green tea nanoparticles in ironized
      mouse model.
AB  - Transfusion in the treatment of thalassemia gives rise to iron deposits in many
      organs. Since there are many obstacles in the use of deferoxamin (DFO) as an iron
      chelating agent, it is important to find another alternative therapy that can act
      as iron chelation. The study aims to compare the histopathological pictures of
      the heart and spleen in iron-induced rats after administration of DFO and
      nanoparticles of green tea extract. The research used experimental research
      design with a post-test only control group. Experimental nano green teas were
      divided into four treatment groups; no diet, DFO supplementation, nano green tea
      supplementation, and a combination of both DFO and green tea. Ferritin and
      glutathione peroxides were used as biochemical parameters, and histopathological
      pictures of the heart and spleen were recorded. The study showed that there was
      significant improvement in the rats receiving DFO and nanoparticles of green tea
      compared with the rats in the no diet group. The study also reported that nano
      green tea has an effect comparable to DFO.

PMID- 28515763
TI  - Poly (ethylene-co-vinyl alcohol)-based polymeric thermo-responsive nanocarriers
      for controlled delivery of epirubicin to hepatocellular carcinoma.
AB  - In this study, poly(ethylene-co-vinyl alcohol) (EVOH) as a novel biocompatible
      polymeric scaffold was surface modified by succinylation to get EVOHS and further
      pegylated to improve structural properties using methoxypolyethylene glycol (5000
      Da) succinate (PEGS) along with targeting with retinoic acid (RA) to get final
      modified active and passive targeted conjugate (PEGS-EVOHS-RA) to evaluate its
      ability in carrying and delivery of epirubicin to hepatocellular carcinoma cell
      lines in response to varying temperatures. In this regard, the PEGS-EVOHS-RA
      conjugate was prepared through the desired chemical reactions and its structure
      was confirmed using 1H-NMR and FT-IR spectra. The micelles were prepared from
      PEGS-EVOHS-RA by dialysis method. The Particle size and zeta potential were
      measured, and entrapment efficacy along with in vitro release efficiency in
      different temperatures were also studied. The structural morphology of optimized
      nanomicelle was studied by transmission electron microscopy micrographs. The
      desired final micelles were evaluated for their toxicity using MTT assay on HepG2
      human hepatocellular carcinoma cell lines at normal (37  degrees C) and elevated
      temperature (45  degrees C). The results revealed that, as the hydrophilicity of
      micelles increased, all characteristic properties improved. Then, these micelles
      can be considered as potentially effective thermo responsive delivery systems for
      targeted delivery of cytotoxic agents to hepatocellular carcinoma.

PMID- 28515764
TI  - The effect of epicatechin on oxidative stress and mitochondrial damage induced by
      homocycteine using isolated rat hippocampus mitochondria.
AB  - Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms
      for neurodegenerative diseases. In this study, we have evaluated the effects of
      epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using
      isolated rat hippocampus mitochondria in vivo. EC (50 mg/kg) was gavaged daily
      for a period of 10 days, starting 5 days prior to Hcy (0.5 MUmol/MUL) intra
      hippocampus injection in rats. Mitochondria were isolated from brain by different
      centrifuge techniques. Mitochondrial function was assayed by MTT test. Also,
      mitochondrial swelling and oxidative stress markers, such as reactive oxygen
      species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy
      induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid
      peroxidation, and decreased GSH were observed after Hcy treatment in isolated
      brain mitochondria. Furthermore, oral administration of EC significantly
      decreased the lipid peroxidation and ROS levels and also increased GSH levels.
      Also, EC treatment significantly improved mitochondrial function. As EC indicated
      protective effects against oxidative stress and mitochondrial damage induced by
      Hcy, it is suggested for further trials for prevention or treatments of
      neurodegenerative disorders such as Alzheimer disease.

PMID- 28515761
TI  - Oligonucleotide aptamers: potential novel molecules against viral hepatitis.
AB  - Viral hepatitis, as an international public health concern, seriously affects
      communities and health system. In recent years, great strides have been taken for
      development of new potential tools against viral hepatitis. Among these efforts,
      a valuable strategy introduced new molecules called "aptamers". Aptamers as
      potential alternatives for antibodies could be directed against any protein in
      infected cells and any components of viral particles. In this review, we will
      focus on recent advances in the diagnosis and treatment of viral hepatitis based
      on aptamer technology. In recent years, various types of aptamers including RNA
      and DNA were introduced against viral hepatitis. Some of these aptamers can be
      utilized for early and precise diagnosis of hepatitis infections and other group
      selected as therapeutic tools against viral targets. Designing diagnostic and
      therapeutic platforms based on aptamer technology is a promising approach in
      viral infections. The obtained aptamers in the recent years showed obvious
      potential for use as diagnostic and therapeutic tools against viral hepatitis.
      Although some modifications to increase the biostability and half-life of
      aptamers are underway, it seems these molecules will be a favorable substitute
      for monoclonal antibody in near future.

PMID- 28515765
TI  - Preparation and in vitro-in vivo evaluation of acyclovir floating tablets.
AB  - In the current study, floating dosage form containing acyclovir was developed to
      increase its oral bioavailability. Effervescent floating tablets containing 200
      mg acyclovir were prepared by direct compression method with three different rate
      controlling polymers including Hydroxypropyl methylcellulose K4M, Carbapol 934,
      and Polyvinylpyrrolidone. Optimized formulation showed good floating properties
      and in vitro drug release characteristics with mean dissolution time and
      dissolution efficacy of about 4.76 h and 54.33%, respectively. X-ray radiography
      exhibited that the tablet would reside in the stomach for about 5 +/- 0.7 h.
      After oral administration of floating tablet containing 200 mg acyclovir, the
      Cmax, Tmax , and AUC0-infinity of optimized gastroretentive formulation were
      found to be 551 +/- 141 ng/mL, 2.75 +/- 0.25 h and 3761 +/- 909.6 ng/mL/h,
      respectively.

PMID- 28515766
TI  - Pancreatic protective and hypoglycemic effects of Vitex agnus-castus L. fruit
      hydroalcoholic extract in D-galactose-induced aging mouse model.
AB  - D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus
      castus (VAC) has potential pancreatic protective effect. Hence, this study was
      designed to evaluate the hypoglycemic and pancreas protective effects of VAC
      hydroalcoholic extract in D-galactose-induced aging female mice. In the present
      experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice
      (weighing 30-35 g) were divided into 6 groups of control, VAC hydroalcoholic
      extract, D-galactose, D-galactose + VAC hydroalcoholic extract, aged, aged + VAC
      hydroalcoholic extract. The aged model was prepared by subcutaneous injection of
      D-galactose for 45 days and, VAC hydroalcoholic extract was gavaged twice a day
      in the last 7 days. 24 h after the last drug and extract administrations, serum
      samples and pancreatic tissues were removed to evaluate experimental and
      histological determinations. Serum glucose level decreased in VAC, D-galactose
      and, aged-treated groups compared to the control (P < 0.05). Insulin level
      increased in VAC and decreased in D-galactose and aged VAC-treated mice compared
      to the control (P < 0.05). Homeostasis model assessment-estimated insulin
      resistance (HOMA-IR) increased in D-galactose, aging, and VAC hydroalcoholic
      extract groups (P < 0.05) and, administration of VAC hydroalcoholic extract
      improved HOMA-IR in D-galactose and aging treated animals. Despite the size of
      pancreatic islets decreased in aged and D-galactose groups, VAC administration
      recovered it. Present data showed that VAC hydroalcoholic extract has
      hypoglycemic and pancreatic protective effects in natural aged and aging model
      mice.

PMID- 28515767
TI  - Cost-effectiveness evaluation of aspirin in primary prevention of myocardial
      infarction amongst males with average cardiovascular risk in Iran.
AB  - Aspirin is one of the certified medicines commonly used for the secondary
      prevention of myocardial infarction (MI). Aspirin side effects and
      gastrointestinal bleeding, in particular, have arisen debates on its use for the
      primary prevention of MI. The present research evaluates the cost-effectiveness
      of the use of aspirin in the primary prevention of MI among Iranian men with
      average cardiovascular disease (CVD) risk, using Markov modeling technique. The
      incremental cost-effectiveness ratios (ICERs) estimated to be 864 USA dollars
      (USD) per quality-adjusted life years (QALY) gained and 782 USD per life years
      gained (LYG) for each patient in the base-case scenario (public tariffs and no
      discounting). This research proves cost-effectiveness of the use of aspirin in
      the primary prevention of MI in targeted population, since the assessed ICERs are
      quite under the recommended threshold by WHO which is one gross domestic product
      (GDP) per capita ($5315.1 for Iran in 2015).

PMID- 28515769
TI  - Inhibitory effects of different fractions of Nepeta satureioides on melanin
      synthesis through reducing oxidative stress.
AB  - Nepeta satureioides Boiss. has been used in traditional medicine of eastern
      countries and is famous for its medicinal properties. The aim of this study was
      to evaluate the effect of methanol (MeOH), n-hexane and dichloromethane (CH2Cl2)
      fractions of the extract on melanin synthesis and oxidative stress in B16F10
      melanoma cell line. The B16F10 cell line viability after treatment with
      increasing concentrations of different fractions of the plant (5-60 MUg/mL) was
      measured using MTT assay. The inhibitory effect on synthesis of melanin, mushroom
      tyrosinase activity, cellular tyrosinase and oxidative stress were determined by
      the colorimetric and fluorometric methods. The data showed that at concentrations
      below 60 MUg/mL, fractions did not show significant toxicity on melanoma cells.
      The amount of melanin synthesis by MeOH and CH2Cl2 fractions and mushroom
      tyrosinase activity by the MeOH fraction declined in B16F10 cells. In addition to
      the capacity of MeOH, n-hexane and CH2Cl2 fractions in decreasing the amount of
      reactive oxygen species (ROS) in melanoma cells, all fractions revealed
      remarkable antioxidant activity. The melanogenesis inhibitory and antioxidant
      effects of N. satureioides on B16F10 cells may suggest this plant as a new
      pharmaceutical agent in reducing skin pigment and skin aging in cosmetic
      industry.

PMID- 28515768
TI  - Effect of acute and long term potassium bromide administration on spatial working
      memory in rat.
AB  - Potassium bromide (KBr), an old antiepileptic agent, is illegally used in
      pharmaceutical or food industries to improve the product appearance. KBr has been
      proven to influence several pathways which are important in memory formation.
      Therefore, the present study aimed to evaluate the effect of KBr on spatial
      working memory using object recognition task (ORT). Rats received a single dose
      of KBr (50, 100 or 150 mg/kg), per oral, in acute treatment. KBr long term
      effects were also studied in animals receiving 50 mg/kg/day of KBr for 28
      consecutive days. At the end of treatments, animals underwent two trials of ORT,
      five min each. In the first trial (T1), animals encountered with two identical
      objects for exploration. After 1 h, the animals were exposed to a familiar and an
      unfamiliar object (T2). The exploration times for discrimination (D) and
      recognition (R) as well as the frequency of exploration for any objects were
      determined. Acute administration of 150 mg/kg of KBr significantly decreased the
      discrimination and recognition indices (RI and DI) (P < 0.01) compared to the
      control. However, lower doses failed to influence the animals' performance in the
      test. In addition, long term administration of KBr remarkably diminished the DI
      and RI and the frequency of exploration (P < 0.05). The results of this study
      indicate that acute doses of KBr as high as 150 mg/kg are required to hamper
      memory function in ORT. However, cognitive impairment occured with lower doses of
      KBr when the duration of treatment is extended.

PMID- 28515771
TI  - Erratum: The structural model of pain, cognitive strategies, and negative
      emotions in functional gastrointestinal disorders.
AB  - [This corrects the article on p. 107 in vol. 21, PMID: 28250784.].

PMID- 28515772
TI  - Retrospective voting and party support at elections: credit and blame for
      government and opposition.
AB  - Retrospective voting is arguably one of the most important mechanisms of
      representative democracy, and whether or not the public holds the government
      accountable for its policy performance has been extensively studied. In this
      paper, we test whether retrospective voting extends to parties in the opposition,
      that is whether and how parties' past performance evaluations affect their vote,
      regardless of whether they were in government or in opposition. Taking advantage
      of a rich set of questions embedded in a representative German national elections
      panel, we update our knowledge on the retrospective voting mechanism by modeling
      retrospective voting at the party level. The findings indicate that the incumbent
      status is not the only criterion for retrospective voting, ultimately suggesting
      that both government and opposition parties can expect credit and blame for their
      conduct and this should provide some impetus for responsive performance of all
      parties.

PMID- 28515770
TI  - High level expression of recombinant human growth hormone in Escherichia coli:
      crucial role of translation initiation region.
AB  - For high-throughput production of recombinant protein in Escherichia coli (E.
      coli), besides important parameters such as efficient vector with strong promoter
      and compatible host, other important issues including codon usage, rare codons,
      and GC content specially at N-terminal region should be considered. In the
      current study, the effect of decreasing the percentage of GC nucleotides and
      optimizing codon usage at N-terminal region of human growth hormone (hGH) cDNA on
      the level of its expression in E. coli were investigated. Mutation in cDNA of hGH
      was performed through site-directed mutagenesis using PCR. Then, the mutant genes
      were amplified and cloned into the expression vector, pET-28a. The new constructs
      were transformed into the BL21(DE3) strain of E. coli and chemically induced for
      hGH expression. At the final stage, expressed proteins were analyzed by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), scanning gel
      densitometry, and western blot. SDS-PAGE scanning gel densitometry assay and
      western blot analysis revealed higher expression level of hGH by using the two
      new expressions constructs (mutant genes vectors with decreasing GC content and
      optimized-codon usage at N-terminal of cDNA) in comparison with wild gene
      expression vector. Obtained results demonstrated that decreasing the GC
      nucleotide content and optimization of codon usage at N-terminal of the hGH cDNA
      could significantly enhance the expression of the target protein in E. coli. Our
      results highlight the important role of both 5' region of the heterologous genes
      in terms of codon usage and also GC content on non-host protein expression in E.
      coli.

PMID- 28515774
TI  - Complexity and algorithms for copy-number evolution problems.
AB  - BACKGROUND: Cancer is an evolutionary process characterized by the accumulation
      of somatic mutations in a population of cells that form a tumor. One frequent
      type of mutations is copy number aberrations, which alter the number of copies of
      genomic regions. The number of copies of each position along a chromosome
      constitutes the chromosome's copy-number profile. Understanding how such profiles
      evolve in cancer can assist in both diagnosis and prognosis. RESULTS: We model
      the evolution of a tumor by segmental deletions and amplifications, and gauge
      distance from profile [Formula: see text] to [Formula: see text] by the minimum
      number of events needed to transform [Formula: see text] into [Formula: see
      text]. Given two profiles, our first problem aims to find a parental profile that
      minimizes the sum of distances to its children. Given k profiles, the second,
      more general problem, seeks a phylogenetic tree, whose k leaves are labeled by
      the k given profiles and whose internal vertices are labeled by ancestral
      profiles such that the sum of edge distances is minimum. CONCLUSIONS: For the
      former problem we give a pseudo-polynomial dynamic programming algorithm that is
      linear in the profile length, and an integer linear program formulation. For the
      latter problem we show it is NP-hard and give an integer linear program
      formulation that scales to practical problem instance sizes. We assess the
      efficiency and quality of our algorithms on simulated instances. AVAILABILITY:
      https://github.com/raphael-group/CNT-ILP.

PMID- 28515775
TI  - Retrospective mortality among refugees from the Central African Republic arriving
      in Chad, 2014.
AB  - BACKGROUND: The Central African Republic has known long periods of instability.
      In 2014, following the fall of an interim government installed by the Seleka
      coalition, a series of violent reprisals occurred. These events were largely
      directed at the country's Muslim minority and led to a massive displacement of
      the population. In 2014, we sought to document the retrospective mortality among
      refugees arriving from the CAR into Chad by conducting a series of surveys.
      METHODS: The Sido camp was surveyed exhaustively in March-April 2014 and a
      systematic sampling strategy was used in the Gore camp in October 2014. The
      survey recall period began November 1, 2013, just before the major anti-Balaka
      offensive. Heads of households were asked to describe their household composition
      at the beginning o f and throughout the recall period. For household members
      reported as dying, further information about the date and circumstances of death
      was obtained. RESULTS: In Sido, 3449 households containing 25 353 individuals
      were interviewed. A total of 2599 deaths were reported, corresponding to a crude
      mortality rate of 6.0/10000 persons/day, and 8% of the population present at the
      beginning of the recall period died. Most (82.4%) deaths occurred among males,
      most deaths occurred in December 2013 and January 2014, and 92% were due to
      violence in the CAR. In Gore, 1383 households containing 8614 individuals were
      interviewed. A total of 1203 deaths were reported, corresponding to a crude
      mortality rate of 3.7/10000 persons/day [95%CI 3.5-3.9], and 12% of the
      population present at the beginning of the recall period died. Most (77.1%)
      deaths occurred among males. As in Sido, most deaths occurred in December 2013
      and January 2014, and 86% of all deaths were due to violence in the CAR.
      CONCLUSIONS: The results of these two surveys describe a part of the toll of the
      violent events of December 2013 and January 2014 in the Central African Republic.

PMID- 28515773
TI  - Building a multipurpose insertional mutant library for forward and reverse
      genetics in Chlamydomonas.
AB  - BACKGROUND: The unicellular green alga, Chlamydomonas reinhardtii, is a classic
      model for studying flagella and biofuel. However, precise gene editing, such as
      Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR
      associated protein (Cas9) system, is not widely used in this organism. Screening
      of random insertional mutant libraries by polymerase chain reaction provides an
      alternate strategy to obtain null mutants of individual gene. But building,
      screening, and maintaining such a library was time-consuming and expensive.
      RESULTS: By selecting a suitable parental strain, keeping individual mutants
      using the agar plate, and designing an insertion cassette-specific primer for
      library screening, we successfully generated and maintained ~150,000 insertional
      mutants of Chlamydomonas, which was used for both reverse and forward genetics
      analysis. We obtained 26 individual mutants corresponding to 20 genes and
      identified 967 motility-defect mutants including 10 mutants with defective
      accumulation of intraflagellar transport complex at the basal body. We also
      obtained 929 mutants defective in oil droplet assembly after nitrogen
      deprivation. Furthermore, a new insertion cassette with splicing donor sequences
      at both ends was also constructed, which increased the efficiency of gene
      interruption. CONCLUSION: In summary, this library provides a multifunctional
      platform both for obtaining mutants of interested genes and for screening of
      mutants with specific phenotype.

PMID- 28515776
TI  - Hormonally active phytochemicals and vertebrate evolution.
AB  - Living plants produce a diversity of chemicals that share structural and
      functional properties with vertebrate hormones. Wildlife species interact with
      these chemicals either through consumption of plant materials or aquatic
      exposure. Accumulating evidence shows that exposure to these hormonally active
      phytochemicals (HAPs) often has consequences for behavior, physiology, and
      fecundity. These fitness effects suggest there is potential for an evolutionary
      response by vertebrates to HAPs. Here, we explore the toxicological HAP
      vertebrate relationship in an evolutionary framework and discuss the potential
      for vertebrates to adapt to or even co-opt the effects of plant-derived chemicals
      that influence fitness. We lay out several hypotheses about HAPs and provide a
      path forward to test whether plant-derived chemicals influence vertebrate
      reproduction and evolution. Studies of phytochemicals with direct impacts on
      vertebrate reproduction provide an obvious and compelling system for studying
      evolutionary toxicology. Furthermore, an understanding of whether animal
      populations evolve in response to HAPs could provide insightful context for the
      study of rapid evolution and how animals cope with chemical agents in the
      environment.

PMID- 28515778
TI  - Evolution of movement rate increases the effectiveness of marine reserves for the
      conservation of pelagic fishes.
AB  - Current debates about the efficacy of no-take marine reserves (MR) in protecting
      large pelagic fish such as tuna and sharks have usually not considered the
      evolutionary dimension of this issue, which emerges because the propensity to
      swim away from a given place, like any other biological trait, will probably vary
      in a heritable fashion among individuals. Here, based on spatially explicit
      simulations, we investigated whether selection to remain in MRs to avoid higher
      fishing mortality can lead to the evolution of more philopatric fish. Our
      simulations, which covered a range of life histories among tuna species (skipjack
      tuna vs. Atlantic bluefin tuna) and shark species (great white sharks vs. spiny
      dogfish), suggested that MRs were most effective at maintaining viable population
      sizes when movement distances were lowest. Decreased movement rate evolved
      following the establishment of marine reserves, and this evolution occurred more
      rapidly with higher fishing pressure. Evolutionary reductions in movement rate
      led to increases in within-reserve population sizes over the course of the 50
      years following MR establishment, although this varied among life histories, with
      skipjack responding fastest and great white sharks slowest. Our results suggest
      the evolution of decreased movement can augment the efficacy of marine reserves,
      especially for species, such as skipjack tuna, with relatively short generation
      times. Even when movement rates did not evolve substantially over 50 years (e.g.,
      given long generation times or little heritable variation), marine reserves were
      an effective tool for the conservation of fish populations when mean movement
      rates were low or MRs were large.

PMID- 28515777
TI  - Experimental evolution to increase the efficacy of the entomopathogenic fungus
      Beauveria bassiana against malaria mosquitoes: Effects on mycelial growth and
      virulence.
AB  - Entomopathogenic fungi such as Beauveria bassiana are currently considered as a
      potential control agent for malaria mosquitoes. The success of such strategies
      depends among others on the efficacy of the fungus to kill its hosts. As B.
      bassiana can use various resources for growth and reproduction, increasing the
      dependency on mosquitoes as a nutritional source may be instrumental for reaching
      this goal. Passage of entomopathogenic fungi through an insect host has been
      shown to increase its virulence. We evaluated the virulence, fungal outgrowth,
      mycelial growth rate, and sporulation rate of two B. bassiana isolates (Bb1520
      and Bb8028) that underwent 10 consecutive selection cycles through malaria
      mosquitoes (Anopheles coluzzii) using an experimental evolution approach. This
      cycling resulted in an altered capacity of evolved B. Bassiana lineages to grow
      on different substrates while maintaining the ability to kill insects. Notably,
      however, there were no significant changes in virulence or speed of outgrowth
      when comparing the evolved lineages against their unevolved ancestors. These
      results suggest that fungal growth and sporulation evolved through successive and
      exclusive use of an insect host as a nutritional resource. We discuss the results
      in light of biocontrol and provide suggestions to increase fungal virulence.

PMID- 28515779
TI  - Higher resource level promotes virulence in an environmentally transmitted
      bacterial fish pathogen.
AB  - Diseases have become a primary constraint to sustainable aquaculture, but
      remarkably little attention has been paid to a broad class of pathogens: the
      opportunists. Opportunists often persist in the environment outside the host, and
      their pathogenic features are influenced by changes in the environment. To test
      how environmental nutrient levels influence virulence, we used strains of
      Flavobacterium columnare, an environmentally transmitted fish pathogen, to infect
      rainbow trout and zebra fish in two different nutrient concentrations. To
      separate the effects of dose and nutrients, we used three infective doses and
      studied the growth of bacteria in vitro. High nutrient concentration promoted
      both the virulence and the outside-host growth of the pathogen, most notably in a
      low-virulence strain. The increase in virulence could not be exhaustively
      explained by the increased dose under higher nutrient supply, suggesting
      virulence factor activation. In aquaculture settings, accumulation of organic
      material in rearing units can locally increase water nutrient concentration and
      therefore increase disease risk as a response to elevated bacterial density and
      virulence factor activation. Our results highlight the role of increased
      nutrients in outside-host environment as a selective agent for higher virulence
      and faster evolutionary rate in opportunistic pathogens.

PMID- 28515780
TI  - Evolution and the duration of a doomed population.
AB  - Many populations are doomed to extinction, but little is known about how
      evolution contributes to their longevity. We address this by modeling an asexual
      population consisting of genotypes whose abundances change independently
      according to a system of continuous branching diffusions. Each genotype is
      characterized by its initial abundance, growth rate, and reproductive variance.
      The latter two components determine the genotype's "risk function" which
      describes its per capita probability of extinction at any time. We derive the
      probability distribution of extinction times for a polymorphic population, which
      can be expressed in terms of genotypic risk functions. We use this to explore how
      spontaneous mutation, abrupt environmental change, or population supplementation
      and removal affect the time to extinction. Results suggest that evolution based
      on new mutations does little to alter the time to extinction. Abrupt
      environmental changes that affect all genotypes can have more substantial impact,
      but, curiously, a beneficial change does more to extend the lifetime of thriving
      than threatened populations of the same initial abundance. Our results can be
      used to design policies that meet specific conservation goals or management
      strategies that speed the elimination of agricultural pests or human pathogens.

PMID- 28515781
TI  - Evolutionary restoration potential evaluated through the use of a trait-linked
      genetic marker.
AB  - Human-driven evolution can impact the ecological role and conservation value of
      impacted populations. Most evolutionary restoration approaches focus on
      manipulating gene flow, but an alternative approach is to manipulate the
      selection regime to restore historical or desired trait values. Here we examined
      the potential utility of this approach to restore anadromous migratory behavior
      in coastal California steelhead trout (Oncorhynchus mykiss) populations. We
      evaluated the effects of natural and anthropogenic environmental variables on the
      observed frequency of alleles at a genomic marker tightly associated with
      migratory behavior across 39 steelhead populations from across California, USA.
      We then modeled the potential for evolutionary restoration at sites that have
      been impacted by anthropogenic barriers. We found that complete barriers such as
      dams are associated with major reductions in the frequency of anadromy-associated
      alleles. The removal of dams is therefore expected to restore anadromy
      significantly. Interestingly, accumulations of large numbers of partial barriers
      (passable under at least some flow conditions) were also associated with
      significant reductions in migratory allele frequencies. Restoration involving the
      removal of partial barriers could be evaluated alongside dam removal and fishway
      construction as a cost-effective tool to restore anadromous fish migrations.
      Results encourage broader consideration of in situ evolution during the
      development of habitat restoration projects.

PMID- 28515783
TI  - Trans-generational plasticity in response to immune challenge is constrained by
      heat stress.
AB  - Trans-generational plasticity (TGP) is the adjustment of phenotypes to changing
      habitat conditions that persist longer than the individual lifetime. Fitness
      benefits (adaptive TGP) are expected upon matching parent-offspring environments.
      In a global change scenario, several performance-related environmental factors
      are changing simultaneously. This lowers the predictability of offspring
      environmental conditions, potentially hampering the benefits of TGP. For the
      first time, we here explore how the combination of an abiotic and a biotic
      environmental factor in the parental generation plays out as trans-generational
      effect in the offspring. We fully reciprocally exposed the parental generation of
      the pipefish Syngnathus typhle to an immune challenge and elevated temperatures
      simulating a naturally occurring heatwave. Upon mating and male pregnancy,
      offspring were kept in ambient or elevated temperature regimes combined with a
      heat-killed bacterial epitope treatment. Differential gene expression (immune
      genes and DNA- and histone-modification genes) suggests that the combined change
      of an abiotic and a biotic factor in the parental generation had interactive
      effects on offspring performance, the temperature effect dominated over the
      immune challenge impact. The benefits of certain parental environmental
      conditions on offspring performance did not sum up when abiotic and biotic
      factors were changed simultaneously supporting that available resources that can
      be allocated to phenotypic trans-generational effects are limited. Temperature is
      the master regulator of trans-generational phenotypic plasticity, which
      potentially implies a conflict in the allocation of resources towards several
      environmental factors. This asks for a reassessment of TGP as a short-term option
      to buffer environmental variation in the light of climate change.

PMID- 28515782
TI  - Ecotypic differentiation under farmers' selection: Molecular insights into the
      domestication of Pachyrhizus Rich. ex DC. (Fabaceae) in the Peruvian Andes.
AB  - Understanding the distribution of crop genetic diversity in relation to
      environmental factors can give insights into the eco-evolutionary processes
      involved in plant domestication. Yam beans (Pachyrhizus Rich. ex DC.) are
      leguminous crops native to South and Central America that are grown for their
      tuberous roots but are seed-propagated. Using a landscape genetic approach, we
      examined correlations between environmental factors and phylogeographic patterns
      of genetic diversity in Pachyrhizus landrace populations. Molecular analyses
      based on chloroplast DNA sequencing and a new set of nuclear microsatellite
      markers revealed two distinct lineages, with strong genetic differentiation
      between Andean landraces (lineage A) and Amazonian landraces (lineage B). The
      comparison of different evolutionary scenarios for the diversification history of
      yam beans in the Andes using approximate Bayesian computation suggests that
      Pachyrhizus ahipa and Pachyrhizus tuberosus share a progenitor-derivative
      relationship, with environmental factors playing an important role in driving
      selection for divergent ecotypes. The new molecular data call for a revision of
      the taxonomy of Pachyrhizus but are congruent with paleoclimatic and
      archeological evidence, and suggest that selection for determinate growth was
      part of ecophysiological adaptations associated with the diversification of the
      P. tuberosus-P. ahipa complex during the Mid-Holocene.

PMID- 28515784
TI  - Improving Saccharomyces cerevisiae ethanol production and tolerance via RNA
      polymerase II subunit Rpb7.
AB  - BACKGROUND: Classical strain engineering methods often have limitations in
      altering multigenetic cellular phenotypes. Here we try to improve Saccharomyces
      cerevisiae ethanol tolerance and productivity by reprogramming its transcription
      profile through rewiring its key transcription component RNA polymerase II (RNAP
      II), which plays a central role in synthesizing mRNAs. This is the first report
      on using directed evolution method to engineer RNAP II to alter S. cerevisiae
      strain phenotypes. RESULTS: Error-prone PCR was employed to engineer the subunit
      Rpb7 of RNAP II to improve yeast ethanol tolerance and production. Based on
      previous studies and the presumption that improved ethanol resistance would lead
      to enhanced ethanol production, we first isolated variant M1 with much improved
      resistance towards 8 and 10% ethanol. The ethanol titers of M1 was ~122 g/L
      (96.58% of the theoretical yield) under laboratory very high gravity (VHG)
      fermentation, 40% increase as compared to the control. DNA microarray assay
      showed that 369 genes had differential expression in M1 after 12 h VHG
      fermentation, which are involved in glycolysis, alcoholic fermentation, oxidative
      stress response, etc. CONCLUSIONS: This is the first study to demonstrate the
      possibility of engineering eukaryotic RNAP to alter global transcription profile
      and improve strain phenotypes. Targeting subunit Rpb7 of RNAP II was able to
      bring differential expression in hundreds of genes in S. cerevisiae, which
      finally led to improvement in yeast ethanol tolerance and production.

PMID- 28515786
TI  - Evaluation of biomass quality in short-rotation bamboo (Phyllostachys pubescens)
      for bioenergy products.
AB  - BACKGROUND: In order to improve the availability of biomass, the concept of
      growing high yield biomass with short rotations and intensive culture has been
      introduced. Bamboo has become a feedstock of potential interest for future energy
      production due to its high productivity and short rotation time. The growth age
      of biomass is an important factor affecting the efficiency of bioconversion and
      pretreatment for bioenergy production. In this regard, more information is
      required on the morphology and chemical composition of bamboo for short-rotation
      biomass production. In this study, we used a compositional assay to compare a
      bamboo of two different growth ages. RESULTS: Bamboo of two different ages showed
      characteristics patterns of morphology, chemical composition, and bioconversion.
      In young-age (2-month-old) bamboo, the pattern of tissue organization was similar
      to that of old-age (3-year-old) bamboo, indicating that the former had reached
      its full height. There were significant differences between young-age and old-age
      bamboo in terms of chemical composition. The glucose contents in old-age bamboo
      did not differ significantly among its internodes. For young-age bamboo, the
      lignin contents were 14.6-18.3%, whereas those of old-age bamboo were
      considerably higher, ranging from 25.4 to 27.1% with increasing syringyl-to
      guaiacyl ratio. The yield of total sugars following enzymatic hydrolysis of young
      age bamboo was approximately eight times. However, following hydrogen peroxide
      acetic acid pretreatment, the results of separate hydrolysis and fermentation and
      simultaneous saccharification and fermentation did not differ significantly
      between young- and old-age bamboo. However, ethanol production was higher in 2
      month old than in 3-year old from initial raw biomass. CONCLUSION: Our data show
      that the production of total sugar from raw material was high in young bamboo
      with low lignin content. With respect to short-rotation biomass, bamboo culm
      harvested after termination of height growth is more appropriate for use as a
      biomass resource to achieve a high yield for bioconversion process.

PMID- 28515785
TI  - Recombinant expression of thermostable processive MtEG5 endoglucanase and its
      synergism with MtLPMO from Myceliophthora thermophila during the hydrolysis of
      lignocellulosic substrates.
AB  - BACKGROUND: Filamentous fungi are among the most powerful cellulolytic organisms
      in terrestrial ecosystems. To perform the degradation of lignocellulosic
      substrates, these microorganisms employ both hydrolytic and oxidative mechanisms
      that involve the secretion and synergism of a wide variety of enzymes.
      Interactions between these enzymes occur on the level of saccharification, i.e.,
      the release of neutral and oxidized products, but sometimes also reflected in the
      substrate liquefaction. Although the synergism regarding the yield of neutral
      sugars has been extensively studied, further studies should focus on the oxidized
      sugars, as well as the effect of enzyme combinations on the viscosity properties
      of the substrates. RESULTS: In the present study, the heterologous expression of
      an endoglucanase (EG) and its combined activity together with a lytic
      polysaccharide monooxygenase (LPMO), both from the thermophilic fungus
      Myceliophthora thermophila, are described. The EG gene, belonging to the
      glycoside hydrolase family 5, was functionally expressed in the methylotrophic
      yeast Pichia pastoris. The produced MtEG5A (75 kDa) featured remarkable thermal
      stability and showed high specific activity on microcrystalline cellulose
      compared to CMC, which is indicative of its processivity properties. The enzyme
      was capable of releasing high amounts of cellobiose from wheat straw, birch, and
      spruce biomass. Addition of MtLPMO9 together with MtEG5A showed enhanced
      enzymatic hydrolysis yields against regenerated amorphous cellulose (PASC) by
      improving the release not only of the neutral but also of the oxidized sugars.
      Assessment of activity of MtEG5A on the reduction of viscosity of PASC and
      pretreated wheat straw using dynamic viscosity measurements revealed that the
      enzyme is able to perform liquefaction of the model substrate and the natural
      lignocellulosic material, while when added together with MtLPMO9, no further
      synergistic effect was observed. CONCLUSIONS: The endoglucanase MtEG5A from the
      thermophilic fungus M. thermophila exhibited excellent properties that render it
      a suitable candidate for use in biotechnological applications. Its strong
      synergism with LPMO was reflected in sugars release, but not in substrate
      viscosity reduction. Based on the level of oxidative sugar formation, this is the
      first indication of synergy between LPMO and EG reported.

PMID- 28515789
TI  - Towards Miscanthus combustion quality improvement: the role of flowering and
      senescence.
AB  - In commercially grown Miscanthus * giganteus, despite imposing a yield penalty,
      postwinter harvests improve quality criteria for thermal conversion and crop
      sustainability through remobilization of nutrients to the underground rhizome. We
      examined 16 Miscanthus genotypes with different flowering and senescence times
      for variation in N, P, K, moisture, ash, Cl and Si contents, hypothesizing that
      early flowering and senescence could result in improved biomass quality and/or
      enable an earlier harvest of biomass (in autumn at peak yield). Ideal crop
      characteristics at harvest are low N and P to reduce future fertilizer inputs,
      low K and Cl to reduce corrosion in boilers, low moisture to reduce spoilage and
      transportation costs, and low Si and ash to reduce slagging and consequent
      operational downtime. Stems and leaves were harvested during summer, autumn and
      then the following spring after overwinter ripening. In spring, stem contents of
      N were 30-60 mg kg-1, P were 203-1132 mg kg-1, K were 290-4098 mg kg-1, Cl were
      10-23 mg kg-1 and moisture were 12-38%. Notably, late senescence resulted in
      increased N, P, K, Cl, moisture and ash contents, and should therefore be avoided
      for thermochemical conversion. Flowering and senescence led to overall improved
      combustion quality, where flowered genotypes tended towards lower P, K, Cl and
      moisture contents; marginally less, or similar, N, Si and ash contents; and a
      similar higher heating value, compared to those that had not flowered. Such
      genotypes could potentially be harvested in the autumn. However, one genotype
      that did not flower in our trial exhibited sufficiently low N and K content in
      autumn to meet the EN plus wood pellet standards for those traits, and some of
      the lowest P, moisture and ash contents in our trial, and is thus a target for
      future research and breeding.

PMID- 28515787
TI  - A computational approach for the functional classification of the epigenome.
AB  - BACKGROUND: In the last decade, advanced functional genomics approaches and deep
      sequencing have allowed large-scale mapping of histone modifications and other
      epigenetic marks, highlighting functional relationships between chromatin
      organization and genome function. Here, we propose a novel approach to explore
      functional interactions between different epigenetic modifications and extract
      combinatorial profiles that can be used to annotate the chromatin in a finite
      number of functional classes. Our method is based on non-negative matrix
      factorization (NMF), an unsupervised learning technique originally employed to
      decompose high-dimensional data in a reduced number of meaningful patterns. We
      applied the NMF algorithm to a set of different epigenetic marks, consisting of
      ChIP-seq assays for multiple histone modifications, Pol II binding and chromatin
      accessibility assays from human H1 cells. RESULTS: We identified a number of
      chromatin profiles that contain functional information and are biologically
      interpretable. We also observe that epigenetic profiles are characterized by
      specific genomic contexts and show significant association with distinct genomic
      features. Moreover, analysis of RNA-seq data reveals that distinct chromatin
      signatures correlate with the level of gene expression. CONCLUSIONS: Overall, our
      study highlights the utility of NMF in studying functional relationships between
      different epigenetic modifications and may provide new biological insights for
      the interpretation of the chromatin dynamics.

PMID- 28515791
TI  - Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and
      bone mineral density in post-menopausal women with type 2 diabetes: a randomized
      controlled trial.
AB  - BACKGROUND: Several antidiabetic therapies affect bone metabolism. Sulfonylureas
      have the lowest impact on bone among oral antidiabetics. The objective of this
      study is to compare the effects of vildagliptin and gliclazide modified release
      (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in
      postmenopausal women with uncontrolled type 2 diabetes (T2D). METHODS: Forty-two
      postmenopausal women with uncontrolled T2D were randomly allocated into
      vildagliptin or gliclazide MR (control) groups. The primary endpoint was the
      change in the BTMs in months 6 and 12 compared with the baseline. The secondary
      endpoint was the variation in the BMD, which was assessed via dual-energy X-ray
      absorptiometry at the lumbar spine, femoral neck and total hip at baseline and
      month 12. RESULTS: After a 12-month treatment, the BTM serum carboxy-terminal
      telopeptide of type 1 collagen increased 0.001 +/- 0.153 ng/mL in the
      vildagliptin group versus 0.008 +/- 0.060 ng/mL in the gliclazide MR group (p =
      0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen
      type I and urinary amino-terminal telopeptide of type 1 collagen remained stable
      in both groups, and there was no statistically significant difference between the
      effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD
      did not change in the vildagliptin or gliclazide MR groups after a 12-month
      treatment (0.000 +/- 0.025 g/cm2 versus -0.008 +/- 0.036, respectively, p =
      0.434). Furthermore, there was a similar lack of change in the femoral neck and
      total hip BMD values in both treatments. CONCLUSIONS: Bone turnover markers and
      BMD remained unchanged after a 12-month treatment in both groups, which suggests
      that vildagliptin has the same safety profile as gliclazide MR on bone
      metabolism. Trial Registration ClinicalTrials.gov number NCT01679899.

PMID- 28515790
TI  - Comparative genomic analysis reveals genetic features related to the virulence of
      Bacillus cereus FORC_013.
AB  - BACKGROUND: Bacillus cereus is well known as a gastrointestinal pathogen that
      causes food-borne illness. In the present study, we sequenced the complete genome
      of B. cereus FORC_013 isolated from fried eel in South Korea. To extend our
      understanding of the genomic characteristics of FORC_013, we conducted a
      comparative analysis with the published genomes of other B. cereus strains.
      RESULTS: We fully assembled the single circular chromosome (5,418,913 bp) and one
      plasmid (259,749 bp); 5511 open reading frames (ORFs) and 283 ORFs were predicted
      for the chromosome and plasmid, respectively. Moreover, we detected that the
      enterotoxin (NHE, HBL, CytK) induces food-borne illness with diarrheal symptom,
      and that the pleiotropic regulator, along with other virulence factors, plays a
      role in surviving and biofilm formation. Through comparative analysis using the
      complete genome sequence of B. cereus FORC_013, we identified both positively
      selected genes related to virulence regulation and 224 strain-specific genes of
      FORC_013. CONCLUSIONS: Through genome analysis of B. cereus FORC_013, we
      identified multiple virulence factors that may contribute to pathogenicity. These
      results will provide insight into further studies regarding B. cereus
      pathogenesis mechanism at the genomic level.

PMID- 28515788
TI  - Genomic imprinting does not reduce the dosage of UBE3A in neurons.
AB  - BACKGROUND: The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with
      maternal-specific expression in neurons and biallelically expressed in all other
      cell types. Both loss-of-function and gain-of-function mutations affecting the
      dosage of UBE3A are associated with several neurodevelopmental syndromes and
      psychological conditions, suggesting that UBE3A is dosage-sensitive in the brain.
      The observation that loss of imprinting increases the dosage of UBE3A in brain
      further suggests that inactivation of the paternal UBE3A allele evolved as a
      dosage-regulating mechanism. To test this hypothesis, we examined UBE3A
      transcript and protein levels among cells, tissues, and species with different
      imprinting states of UBE3A. RESULTS: Overall, we found no correlation between the
      imprinting status and dosage of UBE3A. Importantly, we found that maternal Ube3a
      protein levels increase in step with decreasing paternal Ube3a protein levels
      during neurogenesis in mouse, fully compensating for loss of expression of the
      paternal Ube3a allele in neurons. CONCLUSIONS: Based on our findings, we propose
      that imprinting of UBE3A does not function to reduce the dosage of UBE3A in
      neurons but rather to regulate some other, as yet unknown, aspect of gene
      expression or protein function.

PMID- 28515794
TI  - Influence of a home-based exercise program on the urine pH in elderly female
      subjects: a secondary analysis of a randomized controlled trial.
AB  - BACKGROUND: A low urine pH is a characteristic metabolic feature of metabolic
      syndrome and type 2 diabetes. The purpose of the current study was to investigate
      the effects of a 12-week home-based bench step exercise on the urine pH status of
      elderly female subjects. METHODS: The current study is a secondary analysis of a
      randomized controlled trial (RCT) in which 59 postmenopausal female subjects were
      randomized to either the exercise group (n = 29) or the control group (n = 30).
      The subjects in the exercise group were instructed to perform home-based
      exercises using a bench step at the anaerobic threshold (AT), with a goal of
      performing >=140 min/week at home for 12 weeks. The subjects in the control group
      were instructed to not change their normal lifestyle. Urine was collected after
      overnight fasting, and the urine pH was measured using a urinary test strip. The
      inter-group-differences at baseline and the pre-post changes within groups were
      assessed using the Mann-Whitney U test and Wilcoxon's signed-rank test,
      respectively. Additionally, the difference in the post-intervention urine pH
      levels of the two groups, adjusted for the pre-intervention values (the estimated
      effect size) and the precision (95% confidence intervals) were investigated using
      an analysis of covariance. RESULTS: The pre-post comparison of the urine pH data
      using Wilcoxon's signed-rank test showed a significant increase in the urine pH
      levels of the exercise group (p < 0.05); there was no significant change in the
      urine pH levels of the control group. However, the estimated effect size (0.15)
      was small and the confidence interval straddled 0 (-0.25-0.55). CONCLUSIONS:
      Based on the results of the current secondary analysis of an RCT, we could not
      clearly conclude that exercise has a beneficial effect on the urine pH. Further
      well-designed RCTs should be conducted to determine whether aerobic exercise is
      truly able to ameliorate urine acidification. TRIAL REGISTRATION: The study was
      retrospectively registered in the University Hospital Medical Information Network
      (UMIN) as "Effect of step exercise on aerobic fitness and progression of
      atherosclerosis in the elderly" under the registration number UMIN 000026743 (the
      date of registration: March 28, 2017).

PMID- 28515792
TI  - Mesenchymal stem cell therapy in type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM), which is characterized by the combination of
      relative insulin deficiency and insulin resistance, cannot be reversed with
      existing therapeutic strategies. Transplantation of insulin-producing cells
      (IPCs) was once thought to be the most promising strategy for treating diabetes,
      but the pace from the laboratory to clinical application has been obstructed due
      to its drawbacks. Mesenchymal stem cells (MSCs) harbor differentiation potential,
      immunosuppressive properties, and anti-inflammatory effects, and they are
      considered an ideal candidate cell type for treatment of DM. MSC-related research
      has demonstrated exciting therapeutic effects in glycemic control both in vivo
      and in vitro, and these results now have been translated into clinical practice.
      However, some critical potential problems have emerged from current clinical
      trials. Multi-center, large-scale, double-blind, and placebo-controlled studies
      with strict supervision are required before MSC transplantation can become a
      routine therapeutic approach for T2DM. We briefly review the molecular mechanism
      of MSC treatment for T2DM as well as the merits and drawbacks identified in
      current clinical trials.

PMID- 28515793
TI  - Does the diurnal cycle of cortisol explain the relationship between physical
      performance and cognitive function in older adults?
AB  - BACKGROUND: Regular physical activity is a promising strategy to treat and
      prevent cognitive decline. The mechanisms that mediate these benefits are not
      fully clear but physical activity is thought to attenuate the harmful effects of
      chronic psychological stress and hypercortisolism on cognition. However, the
      circadian pattern of cortisol secretion is complex and it is not known which
      aspects are most closely associated with increased cognitive function and better
      physical performance. This is the first study to simultaneously measure cognitive
      function, the diurnal cycle of salivary cortisol and physical performance in
      older adults, without cognitive impairment (n = 30) and with amnestic Mild
      Cognitive Impairment (aMCI) (n = 30). RESULTS: Regression analysis showed that
      better cognitive function was associated with better physical performance. A
      greater variance in cortisol levels across the day from morning to evening was
      associated with better cognitive function and physical performance. CONCLUSIONS:
      The results support the idea that a more dynamic cortisol secretion pattern is
      associated with better cognitive function and physical performance even in the
      presence of cognitive impairment, but our results could not confirm a mediating
      role in this relationship.

PMID- 28515795
TI  - A Theoretical Investigation on CO Oxidation by Single-Atom Catalysts M1/gamma
      Al2O3 (M=Pd, Fe, Co, and Ni).
AB  - Single-atom catalysts have attracted much interest recently because of their
      excellent stability, high catalytic activity, and remarkable atom efficiency.
      Inspired by the recent experimental discovery of a highly efficient single-atom
      catalyst Pd1/gamma-Al2O3, we conducted a comprehensive DFT study on geometries,
      stabilities and CO oxidation catalytic activities of M1/gamma-Al2O3 (M=Pd, Fe,
      Co, and Ni) by using slab-model. One of the most important results here is that
      Ni1/Al2O3 catalyst exhibits higher activity in CO oxidation than Pd1/Al2O3. The
      CO oxidation occurs through the Mars van Krevelen mechanism, the rate-determining
      step of which is the generation of CO2 from CO through abstraction of surface
      oxygen. The projected density of states (PDOS) of 2p orbitals of the surface O,
      the structure of CO-adsorbed surface, charge polarization of CO and charge
      transfer from CO to surface are important factors for these catalysts. Although
      the binding energies of Fe and Co with Al2O3 are very large, those of Pd and Ni
      are small, indicating that the neighboring O atom is not strongly bound to Pd and
      Ni, which leads to an enhancement of the reactivity of the O atom toward CO. The
      metal oxidation state is suggested to be one of the crucial factors for the
      observed catalytic activity.

PMID- 28515799
TI  - Implementing Mindfulness in the Mainstream: Making the Path by Walking It.
AB  - There is expanding interest in mindfulness-based programs (MBPs) within the
      mainstream. While there are research gaps, there is empirical evidence for these
      developments. Implementing new evidence into practice is always complex and
      difficult. Particular complexities and tensions arise when implementing MBPs in
      the mainstream. MBPs are emerging out of the confluence of different
      epistemologies-contemplative teaching and practice, and contemporary Western
      empiricism and culture. In the process of navigating implementation and
      integrity, and developing a professional practice context for this emerging
      field, the diverse influences within this confluence need careful attention and
      thought. Both contemplative practices, and mainstream institutions and
      professional practice have well-developed ethical understandings and integrity.
      MBPs aim to balance fidelity to both. This includes the need to further develop
      skillful expressions of the underpinning theoretical and philosophical framework
      for MBPs; to sensitively work with the boundary between mainstream and religious
      mindfulness; to develop organizational structures which support governance and
      collaboration; to investigate teacher training, supervision models, and teaching
      competence; to develop consensus on the ethical frameworks on which mainstream
      MBPs rests; and to build understanding and work skillfully with barriers to
      access to MBPs. It is equally important to attend to how these developments are
      conducted. This includes the need to align with values integral to mindfulness,
      and to hold longer-term intentions and directions, while taking small, deliberate
      steps in each moment. The MBP field needs to establish itself as a new
      professional field and stand on its own integrity.

PMID- 28515796
TI  - Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome
      wide copy number analysis in 82 patients without imprinting defects.
AB  - BACKGROUND: Silver-Russell syndrome (SRS) is a rare congenital disorder
      characterized by pre- and postnatal growth failure and dysmorphic features.
      Recently, pathogenic copy number variations (PCNVs) and imprinting defects other
      than hypomethylation of the H19-differentially methylated region (DMR) and
      maternal uniparental disomy chromosome 7 have been reported in patients with the
      SRS phenotype. This study aimed to clarify the frequency and clinical features of
      patients with SRS phenotype caused by PCNVs. METHODS: We performed array
      comparative genomic hybridization analysis using a catalog array for 54 patients
      satisfying the Netchine-Harbison clinical scoring system (NH-CSS) (SRS
      compatible) and for 28 patients presenting with three NH-CSS items together with
      triangular face and/or fifth finger clinodactyly and/or brachydactyly (SRS-like)
      without abnormal methylation levels of 9 DMRs related to known imprinting
      disorders. We then investigated the clinical features of patients with PCNVs.
      RESULTS: Three of the 54 SRS-compatible patients (5.6%) and 2 of the 28 SRS-like
      patients (7.1%) had PCNVs. We detected 3.5 Mb deletion in 4p16.3, mosaic trisomy
      18, and 3.77-4.00 Mb deletion in 19q13.11-12 in SRS-compatible patients, and 1.41
      1.97 Mb deletion in 7q11.23 in both SRS-like patients. Congenital heart diseases
      (CHDs) were identified in two patients and moderate to severe global
      developmental delay was observed in four patients. CONCLUSIONS: Of the patients
      in our study, 5.6% of SRS-compatible and 7.1% of SRS-like patients had PCNVs. All
      PCNVs have been previously reported for genetic causes of contiguous deletion
      syndromes or mosaic trisomy 18. Our study suggests patients with PCNVs, who have
      a phenotype resembling SRS, show a high tendency towards CHDs and/or apparent
      developmental delay.

PMID- 28515800
TI  - Dimensions of Mindfulness and Their Relations with Psychological Well-Being and
      Neuroticism.
AB  - In this study we examined whether differences in the habitual use of mindfulness
      skills were associated with specific well-being and neuroticism aspects. Two
      hundred eleven volunteers aged 21-84 years completed measures of mindfulness,
      neuroticism, psychological well-being (PWB), and subjective well-being (SWB).
      Describing, observing, and acting with awareness (i.e., the mindfulness "what"
      skills) were positively correlated with personal growth, purpose in life, and
      autonomy (i.e., the "core" eudaimonic components of PWB). Nonreactivity and
      nonjudging (i.e., the mindfulness "how" skills) were negatively associated with
      neuroticism aspects, such as withdrawal (e.g., depression) and volatility (e.g.,
      anger). Describing and nonreactivity were the only mindfulness skills
      significantly correlated with the SWB measures. Acting with awareness mediated
      the effect of both withdrawal and volatility on eudaimonic well-being outcomes.
      Describing had consistent mediation effects across all well-being measures, but
      only for the withdrawal aspect. Nonreactivity and nonjudging did not mediated
      withdrawal when considering eudaimonic well-being as outcomes. Mediation effects
      for nonjudging and nonreactivity were found between volatility and SWB markers as
      well as between volatility and self-acceptance, environmental mastery, and
      positive relations with others (i.e., the "other" eudaimonic PWB components). In
      sum, the mindfulness "what" skills were important for eudaimonic well-being,
      especially for internalizing individuals. Authors discuss the usefulness of a
      facet-level analysis of mindfulness for examining incremental validity of some
      facets over others in accounting for different well-being outcomes measures.
      Clinical implications are also discussed.

PMID- 28515797
TI  - Circulating nucleosomes as new blood-based biomarkers for detection of colorectal
      cancer.
AB  - BACKGROUND: Colonoscopy is currently widely accepted as the gold standard for
      detection of colorectal cancer (CRC) providing detection of up to 95% of pre
      cancerous lesions during the procedure. However, certain limitations exist in
      most countries including cost and access to the procedure. Moreover, colonoscopy
      is an invasive technique with risk inherent to the endoscopic procedure. For this
      reason, alternative screening tests, in particular, fecal occult blood-based
      tests, have been widely adopted for frontline screening. Limited compliance to
      colonoscopy and fecal screening approaches has prompted research on blood-based
      tests as an alternative approach to identifying individuals at risk who could
      then be referred for colonoscopy. Increased total levels of nucleosomes in the
      blood have been associated with tumor burden and malignancy progression. Here, we
      report for the first time, CRC-associated epigenetic profiles of circulating cell
      free nucleosomes (cf-nucleosomes). METHODS: Levels of 12 epigenetic cf-nucleosome
      epitopes were measured in the sera of 58 individuals referred for endoscopic
      screening for CRC. RESULTS: Multivariate analysis defined an age-adjusted panel
      of four cf-nucleosomes that provided an AUC of 0.97 for the discrimination of CRC
      from healthy controls with high sensitivity at early stages (sensitivity of 75
      and 86 at 90% specificity for stages I and II, respectively). A second
      combination of four cf-nucleosome biomarkers provided an AUC of 0.72 for the
      discrimination of polyps from the healthy group. CONCLUSIONS: This study suggests
      that a combination of different cf-nucleosome structures analyzed in serum
      samples by a simple ELISA is a promising approach to identify patients at risk of
      CRC.

PMID- 28515798
TI  - Epigenome-wide association of myocardial infarction with DNA methylation sites at
      loci related to cardiovascular disease.
AB  - BACKGROUND: Development of cardiovascular disease (CVD), including coronary
      artery disease, arrhythmia, and ischemic stroke, depends on environmental and
      genetic factors. To investigate the epigenetic basis of myocardial infarction
      (MI), we performed an epigenome-wide association study for this condition in
      elderly Japanese subjects. A total of 192 case subjects with MI and 192 control
      subjects were recruited from hospital attendees and the general population,
      respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from
      whole blood were obtained by analysis with an Infinium HumanMethylation450
      BeadChip. The relation of DNAm sites found to be significantly associated with MI
      to nearby single nucleotide polymorphisms (SNPs) previously shown to be
      associated with CVD was assessed in the control group. FINDINGS: Three DNAm sites
      (cg06642177, cg07786668, cg17218495) showed genome-wide significant associations
      with MI (p = 4.33 * 10-8, 3.96 * 10-10, and 3.77 * 10-8, respectively). Two of
      these sites (cg07786668, cg17218495) still showed such associations after
      adjustment for classical risk factors of MI (p = 1.04 * 10-7 and 6.60 * 10-8,
      respectively). The DNAm sites cg07786668 and cg17218495 are located in ZFHX3
      (zinc finger homeobox 3) and SMARCA4 (SWI/SNF-related, matrix-associated, actin
      dependent regulator of chromatin, subfamily a, member 4) genes, respectively.
      SNPs in ZFHX3 or SMARCA4 that were previously found to be associated with CVD
      were not significantly associated with these DNAm sites in our control subjects.
      CONCLUSIONS: We identified two DNAm sites-cg07786668 in ZFHX3 and cg17218495 in
      SMARCA4- that are independently and significantly associated with MI. Our results
      suggest that the development of MI might be influenced by changes in DNAm at
      these sites via a pathway that differs from that affected by CVD-associated SNPs
      in these genes. The Kita-Nagoya Genomic Epidemiology (KING) study, which was the
      source of control samples in the present study, was registered in
      ClinicalTrials.gov (NCT00262691) on 6 December 2005.

PMID- 28515802
TI  - From cue cards to code rot: In the end, it's not how you acquire the content,
      it's what you do with it.

PMID- 28515803
TI  - Don't miss your 2017 Canadian Urological Association annual meeting.

PMID- 28515801
TI  - Effectiveness and Usability of a Web-Based Mindfulness Intervention for Families
      Living with Mental Illness.
AB  - Families living with mental illness express needs of support and experiences of
      burden that may affect their own health detrimentally and hence also their
      ability to support the patient. Mindfulness-based interventions have shown
      beneficial health effects in both clinical and healthy populations. The aim of
      the current study was to explore the effectiveness and usability of a web-based
      mindfulness program for families living with mental illness, which was first
      tested in a feasibility study. The study was designed as a randomized controlled
      trial with an experiment group and a wait-list control group with assessments on
      primary and secondary outcomes at baseline, post-intervention, and at a 3-month
      follow-up. Significant positive improvements in mindfulness and self-compassion,
      and significant decreases in perceived stress and in certain dimensions of
      caregiver burden were found, with good program usability. Easily accessible
      mindfulness-based interventions may be useful in addressing caregivers' needs of
      support and in preventing further ill health in caregivers. Further studies are
      needed, among others, to further customize interventions and to investigate the
      cost-effectiveness of such programs.

PMID- 28515804
TI  - Study habits of Canadian urology residents: Implications for development of a
      competence by design curriculum.
AB  - INTRODUCTION: The purpose of this study was to evaluate the study habits of
      Canadian urology residents throughout their residency training. METHODS: A survey
      was administered to all final-year Canadian urology residents over a two-year
      period. Sixty-seven respondents answered a survey consisting of 54 questions
      scored on a 10-point Likert score. The survey addressed study habits throughout
      training, motivations for studying, and preferred resources used. RESULTS:
      Dedication to studying was directly correlated with proximity to the Royal
      College of Physicians and Surgeons of Canada (RCPSC) exam. Ninety-six percent of
      residents reported studying over 10 hours per week during their chief year
      compared to 0% during their junior year. As residents progressed in their
      training, preparation for the Royal College exam became the greatest motivator
      for studying. There was considerable variability in study methods and study
      resources used throughout training. In their chief year, residents found such
      resources as the textbook Campbell-Walsh, AUA updates, CUA and AUA guidelines,
      and the study notes of former trainees to be valuable for their preparation.
      Teaching rounds, journal clubs, and reading current urological literature were
      found to be les helpful. Forty-six percent of all residents surveyed indicated
      that they would prefer writing their RCPSC exam one year earlier than the current
      timing. CONCLUSIONS: This study provides insight into study habits of Canadian
      urology residents. This data may be helpful in shaping the future of urology
      training programs and examinations within Canada and elsewhere.

PMID- 28515805
TI  - Is computed tomography-defined obstruction a predictor of urological intervention
      in emergency department patients presenting with renal colic?
AB  - INTRODUCTION: Our objective was to determine whether unilateral calculus-induced
      ureteric obstruction on computed tomography (CT) was independently associated
      with the need for urological intervention and 30-day return to the emergency
      department (ED). METHODS: We performed a retrospective cohort study of patients
      with symptomatic urinary calculi diagnosed by unenhanced helical CT. Stepwise
      regression analysis was used to determine the predictors of urological
      intervention and 30-day return to the ED. Potential predictors assessed included:
      patient demographics, calculus size, calculus location, degree of obstruction,
      analgesic doses, signs and symptoms of infection, serum creatinine, cumulative
      intravenous fluid administered, and the prescription of medical expulsive
      therapy. RESULTS: Of 195 patients, 81 (41.5%) underwent urological intervention.
      The size of the calculus, its location, and the cumulative opioid dose were all
      independent predictors for urological intervention. Every 1 mm increase in
      calculus size increased the likelihood of intervention 2.2 times (odds ratio [OR]
      2.17; 95% confidence interval [CI] 1.67-2.85). Proximal stones were 4.7 times
      more likely to require intervention than distal calculi (OR 0.21; 95% CI 0.09
      0.49). Every 10 mg increase in morphine was associated with a 30% increase in the
      odds of intervention (OR 1.30; 95% CI 1.07-1.58). Degree of obstruction was not
      associated with the need for urological intervention. Finally, none of the
      variables were predictors for 30-day return to the ED. CONCLUSIONS: Although
      stone size, proximal location, and severe pain, as indicated by higher opioid
      doses, were associated with the need for intervention, the degree of obstruction
      did not influence the management of patients with CT-defined urinary calculi.

PMID- 28515806
TI  - Larger proximal ureteral stones with severe pain, rather than computed tomography
      defined ureteral obstruction, are associated with urological intervention.

PMID- 28515808
TI  - Clinical risk-stratification for prostate cancer: Where are we, and where do we
      need to go?

PMID- 28515807
TI  - External validation of the ProCaRS nomograms and comparison of existing risk
      stratification tools for localized prostate cancer.
AB  - INTRODUCTION: The purpose of this study was to perform a direct comparison of
      several existing risk-stratification tools for localized prostate cancer in terms
      of their ability to predict for biochemical failure-free survival (BFFS). Two
      large databases were used and an external validation of two recently developed
      nomograms on an independent cohort was also performed in this analysis. METHODS:
      Patients who were treated with external beam radiotherapy (EBRT) and/or
      brachytherapy for localized prostate cancer were selected from the multi
      institutional Genitourinary Radiation Oncologists of Canada (GUROC) Prostate
      Cancer Risk Stratification (ProCaRS) database (n=7974) and the Centre Hospitalier
      de l'Universite de Montreal (CHUM) validation database (n=2266). The primary
      outcome was BFFS using the Phoenix definition. Concordance index (C-index)
      reported from Cox proportional hazards regression using 10-fold cross validation
      and decision curve analysis (DCA) were used to predict BFFS. RESULTS: C-index
      identified Cancer of the Prostate Risk Assessment (CAPRA) score and ProCaRS as
      superior to the historical GUROC and National Comprehensive Cancer Network (NCCN)
      risk-stratification systems. CAPRA modeled as five and three categories were
      superior to GUROC and NCCN only for the CHUM database. C-indices for CAPRA score,
      ProCaRS, GUROC, and NCCN were 0.72, 0.72, 0.71, and 0.72, respectively, for the
      ProCaRS database, and 0.66, 0.63, 0.57, and 0.60, respectively, for the CHUM
      database. However, many of these comparisons did not demonstrate a clinically
      meaningful difference. DCA identified minimal differences across the different
      risk-stratification systems, with no system emerging with optimal net benefit.
      External validation of the ProCaRS nomograms yielded favourable calibrations of
      R2=0.778 (low-dose rate [LDR]-brachytherapy) and R2=0.868 (EBRT). CONCLUSIONS:
      This study externally validated two ProCaRS nomograms for BFFS that may help
      clinicians in treatment selection and outcome prediction. A direct comparison
      between existing risk-stratification tools demonstrated minimal clinically
      significant differences in discriminative ability between the systems, favouring
      the CAPRA and ProCaRS systems. The incorporation of novel prognostic variables,
      such as genomic markers, is needed.

PMID- 28515809
TI  - Prospective evaluation of anxiety, pain, and embarrassment associated with
      cystoscopy and urodynamic testing in clinical practice.
AB  - INTRODUCTION: We sought to prospectively assess anxiety, pain, and embarrassment
      associated with diagnostic cystoscopy and multi-channel urodynamic study (UDS).
      METHODS: All consecutive patients undergoing diagnostic cystoscopy or UDS in our
      department over a period of nine months were asked to participate. Two anonymous
      auto-administered questionnaires were specifically designed to collect basic
      epidemiological data, document medical history, and assess the quality of
      information provided, along with prevalence and level (0-10 numerical visual
      analog rating scale) of anxiety, pain, and embarrassment experienced before
      and/or during the procedures. Statistical analysis was carried out to identify
      underlying factors that could have influenced patients' experience and ascertain
      potential correlations between anxiety, pain, and embarrassment. RESULTS: 101 and
      185 patients were respectively evaluated immediately after cystoscopy and UDS.
      Multivariate analysis repeatedly showed statistical correlations between anxiety,
      pain, and embarrassment, with regard to prevalence and level of intensity in both
      cystoscopy and UDS populations. Males and young patients were more likely to
      present anxiety, pain, or embarrassment during cystoscopy and UDS. Interestingly,
      patients who reported having received complete information before cystoscopy were
      significantly more likely to experience anxiety (62.6% vs. 20.0%; p=0.009).
      CONCLUSIONS: The present study demonstrated the major impact of gender and age on
      patients' experience. Interestingly, information provided before cystoscopy was
      reported to have a negative impact on patients' perception of anxiety; this could
      be partly prevented by optimizing the way information is provided to patients.

PMID- 28515810
TI  - Avoid the embarrassment: Use the right tools for the right job.

PMID- 28515811
TI  - First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The
      Canadian experience.
AB  - INTRODUCTION: Clinical trial data has shown pazopanib to be non-inferior in
      overall survival (OS) compared to sunitinib as first-line treatment for
      metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate
      outcomes and compare dose-modifying toxicities of mRCC patients treated with
      suntinib or pazopanib in the real-world setting. METHODS: Data were collected on
      mRCC patients using the prospective Canadian Kidney Cancer Information System
      (CKCis) database from January 2011 to November 2015. Statistical analyses were
      performed using Cox regression adjusted for several risk factors and the Kaplan
      Meier method. RESULTS: We identified 670 patients treated with sunitinib (n=577)
      and pazopanib (n=93). There were no significant differences in International
      Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807).
      Patients treated with sunitinib had improved OS compared with pazopanib (median
      31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence
      interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but
      not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130;
      aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib
      were unavailable for this analysis. Patients treated with sunitinib had a higher
      incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease;
      patients treated with pazopanib had a higher incidence of hepatotoxicity.
      CONCLUSIONS: In Canadian patients with mRCC, treatment with sunitinib appears to
      be associated with an improved OS compared to pazopanib in the first-line
      setting. Patient selection factors and the contemporary practice of
      individualized dosing with sunitinib may contribute to these real-world outcomes
      and warrant further investigation.

PMID- 28515812
TI  - Cost-effectiveness of mirabegron compared to tolterodine ER 4 mg for overactive
      bladder in Canada.
AB  - INTRODUCTION: This analysis compared the cost-effectiveness of once-daily
      regimens of mirabegron 50 mg and generic tolterodine ER 4 mg in a hypothetical
      cohort of previously treated patients with overactive bladder (OAB) in Canada.
      METHODS: A Markov model was developed to represent different health states
      according to OAB symptoms (frequency, incontinence), presence/absence of adverse
      events (AEs; dry mouth, constipation, blurred vision), and treatment status (on
      treatment, discontinue treatment, restart previous treatment). The time horizon
      used was one year, with monthly transitions between health states. The model was
      populated using data from a phase 3, placebo-controlled trial of mirabegron that
      included tolterodine as an active comparator (SCORPIO), as well as other
      published literature and expert opinion. Cost-effectiveness was calculated from
      Canadian public payer (based on Quebec list prices) and societal perspectives.
      RESULTS: The incremental one-year cost per patient for mirabegron over
      tolterodine was $182 CAD and $157 CAD from the payer and societal perspectives,
      respectively. The incremental quality-adjusted life year (QALY) gain for
      mirabegron was 0.0066 when using EQ-5D health-state utilities. Mirabegron was
      cost-effective compared with tolterodine, from both payer and societal
      perspectives, and remained cost-effective vs. tolterodine across the majority of
      sensitivity analyses. The model was based on limited clinical trial evidence
      supplemented with expert opinion and assumptions; a select number of OAB
      symptoms, AEs, and direct and indirect medical costs associated with OAB; and a
      timeframe of only one year. CONCLUSIONS: From the payer and societal
      perspectives, the health economic model indicates that in Canada, mirabegron is a
      cost-effective treatment strategy compared with tolterodine, leading to improved
      health outcomes (QALYs) at an acceptable incremental cost.

PMID- 28515813
TI  - Transperitoneal laparoscopic nephrectomy: Assessing complication risk in cases of
      previous abdominal surgery.
AB  - INTRODUCTION: We aimed to assess the effect of previous abdominal surgery on
      perioperative outcomes in patients undergoing transperitoneal laparoscopic
      partial (LPN) or radical (LRN) nephrectomy for renal masses. METHODS: We
      retrospectively reviewed all cases of LPN and LRN for renal masses at our
      institution between 2008 and 2014. Patients were divided in two groups, those
      with and without prior abdominal surgery. Four perioperative outcomes were
      compared, namely, operative time (OT), estimated blood loss (EBL), length of stay
      (LOS), and 30-days complications rate. A subanalysis was performed to address the
      impact of previous open cholecystectomy on right LPN or LRN. RESULTS: Of 293
      patients identified, 146 (49.8%) had previous abdominal surgery. In univariate
      analysis, no differences in operative time (136 vs. 144 minutes; p=0.154), EBL
      (88 vs. 100 mL; p=0.211), or 30-day complication rate (24 vs. 14%; p=0.069) were
      recorded between the groups. Only LOS favoured patients without previous
      abdominal surgery (3 vs. 4 days; p=0.001). In multivariate analysis, prior
      abdominal surgery was not associated with an increased OT, EBL, LOS, or
      complication rate. The analysis of right nephrectomies showed increased OT (148
      vs. 128 minutes; p=0.049) and complication rate (42 vs. 16%; p=0.004) for
      patients with past open cholecystectomy compared to those without. Multivariate
      analysis revealed that prior open cholecystectomy was associated with a longer
      LOS (ORmedian=2.7 [1.2-8.0]) and an increased risk of complications (ORmedian=4.5
      [1.6-10.5]). CONCLUSIONS: In this cohort, previous abdominal surgery was not
      associated with worse perioperative outcomes after transperitoneal LPN and LRN
      for renal masses. However, previous open cholecystectomy resulted in a higher
      risk of complication and a longer LOS in patients undergoing right laparoscopic
      nephrectomy.

PMID- 28515815
TI  - ?

PMID- 28515814
TI  - A review of routinely collected data studies in urology: Methodological
      considerations, reporting quality, and future directions.
AB  - Studies using routinely collected data (RCD) are common in the urological
      literature; however, there are important considerations in the creation and
      review of RCD discoveries. A recent reporting guideline (REporting of studies
      Conducted using Observational Routinely-collected health Data, RECORD) was
      developed to improve the reporting of these studies. This narrative review
      examines important considerations for RCD studies. To assess the current level of
      reporting in the urological literature, we reviewed all the original research
      articles published in Journal of Urology and European Urology in 2014, and
      determined the proportion of the RECORD checklist items that were reported for
      RCD studies. There were 56 RCD studies identified among the 608 articles. When
      the RECORD items were considered applicable to the specific study, they were
      reported in 52.5% of cases. Studies most consistently (>80% of them) reported the
      names of the data sources, the study time frame, the extent to which the authors
      could access the database source, the patient selection, and discussed missing
      data. Few studies (<25%) discussed validation of key coding elements, details on
      data-linkage, data-cleaning, the impact of changing eligibility over time, or
      provided the complete list of coding elements used to define key study variables.
      Reporting factors specifically relevant in RCD studies may serve to increase the
      quality of these studies in the urological literature. With increased
      technological integration in healthcare and the proliferation of electronic
      medical records, RCD will continue to be an important source for urological
      research.

PMID- 28515816
TI  - Impact of smartphone digital photography, email, and media communication on
      emergency room visits post-hypospadias repair.
AB  - INTRODUCTION: Advances in communication technology are shaping our medical
      practice. To date, there is no clear evidence that this mode of communication
      will have any effect on unnecessary postoperative emergency room (ER) visits. We
      aim to evaluate the effect of email and media communication with application of
      smartphone digital photography on post-hypospadias repair ER visit rates.
      METHODS: This prospective cohort study included all patients who underwent
      hypospadias repair performed by a single surgeon from October 2014 to November
      2015. Patients were categorized into two groups: Group A consented for smartphone
      photography and email communication and Group B declined. Reason for ER visits
      within 30 days postoperatively was assessed by another physician, who was blinded
      of patient group assignment. The reasons were categorized as: unnecessary ER
      visit, indicated ER visit, or visit unrelated to hypospadias surgery. Chi-square
      test and T-test were used for statistical analysis. Relative risk (RR) and
      corresponding 95% confidence interval (CI) were also calculated. Statistical
      significance was set at p<0.05. RESULTS: Over a 14-month period, 96 patients
      underwent hypospadias repair (81 in Group A, 15 in Group B 5). No significant
      difference was noted between groups for overall ER return rate (RR 0.46, 95% CI
      0.21, 1.0). However, the number of ER visits for wound check not requiring
      intervention was significantly lower in Group A than in Group B (RR 0.14, 95% CI
      0.035, 0.56); likewise, a higher number of ER visits requiring intervention was
      noted in Group A compared with Group B, although statistically this was not
      significant (RR 1.67, 95% CI 0.23, 12.21). CONCLUSIONS: Email communication with
      the use of smartphone digital photography significantly reduced the number of
      unnecessary ER visits for post-hypospadias wound checks.

PMID- 28515817
TI  - Systematic review of the potential role of cannabinoids as antiproliferative
      agents for urological cancers.
AB  - INTRODUCTION: The palliative effects of cannabis sativa (marijuana), which
      include appetite stimulation, attenuation of nausea and emesis, and pain relief,
      are well known. The active components of cannabis sativa (cannabinoids) and their
      derivatives have received growing interest due to their diverse pharmacological
      activities, such as cell growth inhibition and tumour regression. The aim of this
      review is to look at the current evidence on the antiproliferative effects of
      cannabinoids in urological malignancies, including renal, prostate, bladder, and
      testicular cancers. METHODS: We conducted a systematic review of studies
      exploring the effect of cannabinoids on tumour activity, including all study
      types except expert opinions. A formal search was run on Medline database from
      1946 to September 2016, along with a hand-search on PubMed for relevant studies.
      RESULTS: The search yielded a total of 93 studies from Medline and PubMed, of
      which 23 studies were included in the final analysis. To date, there are various
      in vitro studies elucidating the potential mechanism of action of cannabinoids
      for urological cancers, along with population-based studies specifically for
      testicular malignancies. To date, no clinical trials have been conducted for
      urological cancer patients. CONCLUSIONS: These results demonstrate that the role
      of endocannabinoids for urological malignancies is an area of active research.
      Further research is required not only to evaluate the crosstalk between cancer
      signaling pathways and cannabinoids, but also large randomized clinical studies
      with urological patients need to be conducted before cannabinoids can be
      introduced as potential therapeutic options for urological neoplasms.

PMID- 28515818
TI  - Pharmacogenomic Testing for Psychotropic Medication Selection: A Systematic
      Review of the Assurex GeneSight Psychotropic Test.
AB  - BACKGROUND: A large proportion of the Ontario population lives with a diagnosed
      mental illness. Nearly 5% of Ontarians have major depressive disorder, and
      another 5% have another type of depressive disorder, bipolar disorder,
      schizophrenia, anxiety, or some other disorder not otherwise specified.
      Medications are commonly used to treat mental illness, but choosing the right
      medication for each patient is challenging, and more than 40% of patients
      discontinue their medication within 90 days because of adverse effects or lack of
      response. The Assurex GeneSight Psychotropic test is a pharmacogenomic panel that
      provides clinicians with a report to guide medication selection that is unique to
      each patient based on their individual genetic profile. However, it is uncertain
      whether guided treatment using GeneSight is effective compared with unguided
      treatment (usual care). METHODS: We performed a systematic review to identify
      English-language studies published before February 22, 2016, that compared
      GeneSight-guided care and usual care among people with mood disorders, anxiety,
      or schizophrenia. Primary outcomes of interest were prevention of suicide,
      remission of depression symptoms, response to depression therapy, depression
      score, and quality of life. Secondary outcomes of interest were impact on
      therapeutic decisions and patient and clinician satisfaction. Risk of bias was
      evaluated, and the quality of the evidence was assessed using the Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) working group
      criteria. RESULTS: Four studies met the inclusion criteria. These studies used a
      version of GeneSight that included the CYP2D6, CYP2C19, CYP1A2, SLC6A4, and HTR2A
      genes; one of the studies also included CYP2C9. Patients who received the
      GeneSight test to guide psychotropic medication selection had improved response
      to depression treatment, greater improvements in measures of depression, and
      greater patient and clinician satisfaction compared with patients who received
      treatment as usual. We observed no differences in rates of complete remission
      from depression. The findings were based on GRADE assessment of low to very low
      quality evidence, and the body of evidence had several limitations: the included
      studies used an older version of GeneSight and were limited to a population with
      major depression, so results may not be generalizable to other versions of the
      test or different populations such as patients with anxiety or schizophrenia.
      CONCLUSIONS: There is uncertainty about the use of GeneSight Psychotropic
      pharmacogenomic genetic panel to guide medication selection. It was associated
      with improvements in some patient outcomes, but not others. As well, our
      confidence in these findings is low because of limitations in the body of
      evidence.

PMID- 28515819
TI  - Sub-Clinical Hypothyroidism and Its Association With Increased Cardiovascular
      Mortality: Call for Action.
AB  - Thyroid hormones play an important role in regulating different functions
      regarding metabolism and performance in multiple organs. Any change in the
      thyroid hormones axis can lead to profound effect on the vital organ stability
      especially the cardiovascular system. Hypothyroidism is classified according to
      the clinical presentation as overt and subclinical. Currently, there exists a
      paucity of evidence on the beneficial effects of thyroxine hormone replacement on
      cardiovascular mortality outcomes in subclinical hypothyroidism. Also, the
      clinical relevance of measuring and treating supra-normal thyroid-stimulating
      hormone levels in newly diagnosed heart failure patients with preserved ejection
      fraction requires further study. Here we review the current evidence regarding
      the prognostic significance of sub-clinical hypothyroidism in patients with heart
      failure with preserved ejection fraction.

PMID- 28515820
TI  - Arterial Velocity Pulse Index as a Novel Marker of Atherosclerosis Using Pulse
      Wave Analysis on High Sensitivity Troponin T in Hypertensive Patients.
AB  - BACKGROUND: The arterial velocity pulse index (AVI) is explored as a novel marker
      of atherosclerosis using pulse wave analysis in clinical settings. Recent
      clinical studies have reported that the level of high-sensitivity troponin T (hs
      cTnT) is an important biomarker in hypertensive patients. The aim of this study
      was to clarify the impact of AVI on hs-cTnT in these patients. METHODS: This
      study enrolled 455 hypertensive outpatients (181 males and 274 females; mean age,
      65 +/- 11 years (mean +/- standard deviation)) without a history of
      cardiovascular events. AVI and hs-cTnT levels were measured using a commercial
      device, and relations among various clinical parameters, including AVI and hs
      cTnT, were examined. RESULTS: Hs-cTnT was detected in 405 patients (89.0%). AVI
      was significantly higher in patients with detectable hs-cTnT than in those
      without (28 +/- 7 vs. 24 +/- 8, respectively, P < 0.001). In patients with
      detectable hs-cTnT, there was a significant positive correlation between AVI and
      hs-cTnT (r = 0.42, P < 0.001). Furthermore, multiple regression analyses revealed
      that AVI was an independent variable when hs-cTnT was used as a subordinate
      factor. On the other hand, hs-cTnT age, Cornell electrocardiographic voltage,
      height, urinary albumin excretion, pulse rate, and derivatives of reactive oxygen
      metabolites test were independent variables when AVI was used as a subordinate
      factor. CONCLUSION: The results of this study indicate that AVI reflects features
      of arterial wave reflection and is an important factor for hs-cTnT elevation in
      hypertensive patients.

PMID- 28515822
TI  - Primary Percutaneous Coronary Intervention Angioplasty of Occluded Twin
      Circumflex Coronary Artery in a Patient of Acute Inferior Wall Myocardial
      Infarction: A Rare Anomaly.
AB  - Anomalies of the coronary arteries are reported in 1-2% of patients among
      diagnostic angiogram. Dual origin of a circumflex from both sinuses is extremely
      rare among them. We report a case of a patient who underwent primary percutaneous
      coronary intervention for acute inferior wall myocardial infarction where left
      coronary injection demonstrated normal obtuse marginal and right coronary
      injection demonstrated normal right coronary artery (RCA). On further probing, an
      anomalous left circumflex (LCx) artery was seen arising from RCA ostium which was
      subsequently cannulated and revascularized by deployment of 2.75 * 26 mm Xience
      Prime drug-eluting stent (Abott Vascular, USA). Herein, we report for the first
      time primary percutaneous coronary intervention of twin circumflex and also
      illustrate that anomalous circumflex can be missed if it arises from RCA ostium
      and if not probed carefully.

PMID- 28515821
TI  - Left Ventricular Velocity of Propagation: A Useful Non-Invasive Measurement When
      Assessing Hemodynamic Alterations in Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Left ventricular (LV) velocity of propagation (Vp) has been shown to
      be inversely related to the LV relaxation time constant. We sought to examine Vp
      from a group of chronic pulmonary hypertension (cPH) patients and compare these
      values to Vp obtained in normal individuals and patients with known LV diastolic
      dysfunction (LVDD). METHODS: Echo-Doppler data and Vp measurements were
      retrospectively collected from all patients. The studied population was divided
      into four groups. Group I comprised of 15 patients with normal LV diastole, group
      II included 27 patients with stage 1 LVDD, group III was made up of 27 patients
      with stage 2 LVDD, and group IV included 66 patients with cPH. RESULTS: In the
      cPH population studied, patients had smaller end-diastolic LV cavities with the
      highest Vp values but their early mitral inflow to Vp ratios were not different
      from healthy controls. In addition, Vp values and pulmonary wedge capillary
      pressures were significantly associated in patients with LV dysfunction or
      pulmonary hypertension (P < 0.01). CONCLUSIONS: LVVp might be a useful non
      invasive measurement to be routinely obtained in cPH patients as it probably not
      only reflects the compressive forces being exerted on the LV, known to increase
      Vp, but also might be quite useful for the non-invasive assessment of pulmonary
      capillary wedge pressures in these patients.

PMID- 28515823
TI  - Lupus-Negative Libman-Sacks Endocarditis Complicated by Catastrophic
      Antiphospholipid Syndrome.
AB  - Libman-Sacks endocarditis is characterized by sterile and verrucous lesions that
      predominantly affect the aortic and mitral valves. In most cases, patients do not
      have significant valvular dysfunction. However, patients with significant
      valvular dysfunction may present with serious complications such as cardiac
      failure, arrhythmias, and thromboembolic events. Recently, association of Libman
      Sacks endocarditis with antiphospholipid antibody syndrome (APS) has been made.
      APS is most commonly defined by venous and arterial thrombosis, recurrent
      pregnancy loss, and thrombocytopenia. While the syndrome can be a primary
      syndrome, it is usually secondary to systemic lupus erythematosus. Catastrophic
      antiphospholipid syndrome (CAPS) can be a life-threatening presentation of APS
      and can occur in 1% of patients with antiphospholipid syndrome. We present a very
      rare case of a young female patient with lupus-negative Libman-Sacks endocarditis
      complicated by CAPS.

PMID- 28515824
TI  - Cardiogenic Shock, Acute Severe Mitral Regurgitation and Complete Heart Block
      After Cavo-Tricuspid Isthmus Atrial Flutter Ablation.
AB  - Radiofrequency (RF) ablation is the first-line management of cavo-tricuspid
      isthmus dependent atrial flutter. It has been performed with 95% success rate.
      Adverse events are very rare. We report the first case of acute severe mitral
      regurgitation (MR) and complete heart block developed after successful atrial
      flutter ablation. A 62-year-old female with mild MR presented with palpitations.
      Surface electrocardiogram was suggestive of isthmus dependent atrial flutter. A
      duodecapolar mapping catheter showed an atrial flutter with cycle length of 280
      ms. An 8 mm tipped Thermistor RF ablation catheter was placed at the cavo
      tricuspid isthmus. RF energy was delivered as the catheter was dragged to the
      inferior vena cava. Temperature limit was 60  degrees C; the power output limit
      was 60 W. The patient converted to sinus rhythm with the first ablation line. Bi
      directional block was recorded. Two additional ablation lines lasting 60 - 120 s
      were delivered. The patient started having chest pain and developed complete
      heart block with no escape rhythm. She became hypotensive and was immediately
      paced from the right ventricle. There were no signs of pericardial tamponade.
      Emergent bedside echo demonstrated severe MR with a retracted posteromedial
      mitral valve leaflet. She was 100% paced and EKG changes could not be assessed.
      Based on the sudden onset chest pain, hypotension, complete heart block and acute
      severe MR after ablation, the right coronary artery occlusion was suspected. She
      was immediately transferred to the catheterization laboratory. Coronary
      angiography revealed a total occlusion of the posterolateral branch from the
      right coronary artery. Balloon angioplasty and coronary artery stenting was
      performed. Complete heart block subsequently resolved. Subsequent bedside
      echocardiogram showed marked improvement of the MR. Patients with smaller body
      size have smaller hearts and more likely to have injury from RF current. Higher
      energy penetrates deeper and causes more tissue damage. The use of lower
      temperature limits (55  degrees C) and lower energy (60 W) for small, elderly,
      and female patients is encouraged.

PMID- 28515825
TI  - Late Presentation of Aortic Aneurysm and Dissection Following Cardiac
      Catheterization.
AB  - We report a 63-year-old female with hypertension, hyperlipidemia, and prior
      pacemaker insertion for atrial fibrillation with symptomatic bradycardia, who was
      admitted with substernal chest pressure and diaphoresis. Her electrocardiogram
      revealed atrial fibrillation with demand ventricular pacing and her cardiac
      biomarkers were negative for acute coronary syndrome. Echocardiogram revealed
      normal left ventricular systolic function and normal aortic root diameter.
      Coronary angiography revealed 60-70% obtuse marginal lesion, otherwise mild
      disease. She was treated medically and discharged in stable condition. She was
      readmitted 1 month later with recurring chest pain, and shortness of breath which
      started shortly after her most recent discharge. Blood pressure was 152/93 mm Hg,
      and heart rate was 105 bpm. BNP was elevated at 1,400 pg/mL, and other cardiac
      biomarkers were negative. She was treated with diuretics, which resulted in
      decrease of her blood pressure to 81/51 mm Hg. Repeat echocardiogram revealed
      severely dilated aortic root, measuring 6.7 cm, with aortic dissection flap and
      moderate to severe aortic regurgitation. CT angiogram revealed aortic dissection
      extending proximally to the aortic root above the coronary ostia and distally to
      the left subclavian artery takeoff. She underwent surgery; she, however, could
      not be weaned off from cardiopulmonary bypass and died in the operating room.
      This case illustrates the importance of having a high index of suspicion for
      iatrogenic aortic dissection following cardiac catheterization as a cause of
      recurrence of cardiac symptoms, as early detection may help avert a catastrophic
      outcome, as we report in our patient.

PMID- 28515826
TI  - Successful Restoration of Complete Heart Block to Normal Sinus Rhythm by Primary
      Angioplasty of Dual Left Anterior Descending Artery.
AB  - Dual left anterior descending (LAD) artery is a rare coronary anomaly. We present
      a patient with a rare case of dual LAD, smaller one arising from the left main
      coronary stem and larger one from right coronary artery who presented with acute
      anterior wall myocardial infarction with complete heart block (CHB). Temporary
      pacemaker was implanted and coronary angiogram revealed critical occlusion of
      proximal LAD which was subsequently revascularized by primary angioplasty using
      drug-eluting stent (Xience prime, 2.75 * 23 mm) leading to recovery of CHB and
      restoration to normal rhythm. To the best of our knowledge, this is the first
      reported case of dual LAD presenting with CHB treated by primary angioplasty
      reported in the literature.

PMID- 28515827
TI  - Transient Left Bundle Branch Block due to Severe Hyperkalemia.
AB  - Hyperkalemia is a potentially life-threatening electrolyte imbalance that can
      lead to sudden death from cardiac arrhythmias and asystole. We present a case of
      transient left bundle branch block pattern on an electrocardiogram (ECG)
      secondary to hyperkalemia in a patient with history of end-stage renal disease. A
      52-year-old man presented to the emergency room (ER) with chief complaints of
      weakness and lethargy after missing his regularly scheduled session of
      hemodialysis. A 12-lead ECG in the ER showed sinus tachycardia at 118 beats/min,
      wide QRS complexes, peaked T waves and left bundle branch block-like pattern. The
      initial basic metabolic panel revealed a serum potassium level of 8.8 mEq/L.
      Subsequently, the patient underwent emergent hemodialysis. Serum chemistry after
      hemodialysis showed improvement in serum potassium to 4.3 mEq/L. Repeat ECG
      performed after correcting potassium showed dissolution of left bundle branch
      block finding.

PMID- 28515828
TI  - Primary Percutaneous Coronary Intervention Using BaLloon-Assisted Sliding and
      Tracking (BLAST) of Diagnostic Catheter to Negotiate Double Hairpin Loop of
      Radial Artery.
AB  - During transradial intervention, sharp edge of the guide catheter tip may act
      like a "razor-blade" and can prevent the catheter navigation especially in
      situation like double hair pin loop. Here, we report primary percutaneous
      coronary intervention (PCI) through diagnostic catheter using an innovative
      technique, balloon-assisted sliding and tracking (BLAST), to overcome this double
      hairpin loop, thus saving time and contrast volume.

PMID- 28515829
TI  - Semiparametric Random Effects Models for Longitudinal Data with Informative
      Observation Times.
AB  - Longitudinal data frequently arise in many fields such as medical follow-up
      studies focusing on specific longitudinal responses. In such situations, the
      responses are recorded only at discrete observation times. Most existing
      approaches for longitudinal data analysis assume that the observation or follow
      up times are independent of the underlying response process, either completely or
      given some known covariates. We present a joint analysis approach in which
      possible correlations among the responses, observation and follow-up times can be
      characterized by time-dependent random effects. Estimating equations are
      developed for parameter estimation and the resulting estimates are shown to be
      consistent and asymptotically normal. A simulation study is conducted to assess
      the finite sample performance of the approach and the method is applied to data
      arising from a skin cancer study.

PMID- 28515831
TI  - The Relationship of Living Environment with Behavioral and Fitness Outcomes by
      Sex: an Exploratory Study in College-aged Students.
AB  - Although physical activity (PA) is associated with several health benefits, there
      is a marked decline during college years, which is an influential period for the
      development of health behaviors. This study examined the relationship of
      neighborhood and living environment with behavioral (PA and sedentary behavior)
      and fitness outcomes by sex. Participants were college students that participated
      in a fitness assessment, followed by a survey that measured self-reported
      exercise and perception of one's environment (sidewalks, crime, traffic, access
      to PA resources in their neighborhood and/or apartment complex). Pearson
      correlations examined the relationship between behavioral (moderate and vigorous
      PA, sedentary behavior, active travel) and fitness outcomes (VO2max, percent body
      fat, body mass index, push-ups, curl-ups, blood lipids and glucose) with
      environmental measures separately by sex. Among participants (n=444; female=211,
      male n=234) environment was significantly related to PA and fitness, with noted
      differences by sex. For males, seeing others exercising in the neighborhood and
      in their apartment complex, using neighborhood bike lanes, crime and the number
      of PA resources at their apartment complex were associated with behavioral and
      fitness outcomes. Among females, sidewalks in the neighborhood, seeing others
      exercising, using neighborhood bike lanes and number of PA apartment complex
      resources were significantly correlated with fitness and behavioral outcomes.
      These findings suggest a possible relationship between students' objectively
      measured fitness and their environment for PA. Future implications include the
      development of policies to create student housing that supports physical activity
      and expansion of campus wellness initiatives to off-campus locations.

PMID- 28515832
TI  - A Low Dose Caffeine and Carbohydrate Supplement does not Improve Athletic
      Performance during Volleyball Competition.
AB  - Dietary supplements are widely used to enhance sport performance and the
      combination of carbohydrate and caffeine (CHO+CAF) has yielded particularly high
      performance gains. Though the effects of a CHO+CAF supplement have been studied
      in a laboratory environment, little research exists on the effects of
      supplementation during competition. Therefore, the purpose of this study was to
      determine the effects of a CHO+CAF supplement on athletic performance in
      competition. Eight female collegiate volleyball players completed three testing
      sessions under three different conditions separated by approximately one week
      each: CHO+CAF supplement, placebo (PBO), and control (CTL) using a randomized,
      cross-over design. Blood glucose (BG) was assessed prior to supplementation and
      immediately after set three. The supplement and PBO were administered prior to
      play and between sets two and three. Following three sets of play, three
      performance tests were completed: vertical jump (VJ), agility (AGL), and repeated
      30-m sprint ability (RSA). While CHO+CAF supplementation significantly increased
      BG, the performance tests were not different (p>.05) among the testing
      conditions. These findings suggest that the amount of the supplement used in this
      study is not beneficial to VJ, AGL, and RSA in female volleyball players. As
      these performance tests were largely anaerobic and non-glycolytic in nature, the
      ergogenicity of the supplement may have been underutilized. Additionally, coaches
      and athletes should not only be aware of what ingredients are in the supplements
      they choose, but the amount of those ingredients as they may modify the efficacy
      of the supplement to impact performance.

PMID- 28515834
TI  - Better Health-Related Fitness in Youth: Implications for Public Health
      Guidelines.
AB  - Public health guidelines for physical activity (PA) behaviors are being updated
      with 2018 as a proposed release date. Currently, >=60 minutes of daily PA are
      recommended for youth. Thus, the purpose of this study was to investigate the
      association between reported days of aerobic PA and health-related fitness (HRF).
      Participants included 4448 students in grades 6-8. Self-reported days of >=60
      minutes of aerobic PA was obtained. HRF was assessed with FitnessGram.
      Discriminant analysis indicated that weekly days of aerobic PA related to HRF.
      Adolescents who participated in >=5 days of weekly aerobic PA generally had
      better fitness results than those with <=4 days. Chi-square analyses indicated
      the highest percentages of adolescents in the FitnessGram Healthy Fitness ZoneTM
      (HFZ) for each test item were those with >=5 days of aerobic PA. These findings
      provided initial support that the impact of aerobic PA on HRF plateaus at 5 days
      per week. Thus, adolescents may be able to improve HRF even if they do not meet
      the currently recommended guidelines for daily PA.

PMID- 28515833
TI  - Time Course of Changes in Neuromuscular Responses at 30% versus 70% 1 Repetition
      Maximum during Dynamic Constant External Resistance Leg Extensions to Failure.
AB  - The purpose of the current study was to examine the time course of changes in
      neuromuscular responses from the vastus medialis (VM) during low versus high
      intensity dynamic constant external resistance (DCER) leg extension muscle
      actions to failure. Thirteen men performed DCER leg extensions to failure at 30%
      and 70% 1-repetition maximum (1-RM) as well as 1-RM measurements pretest and
      posttest. Electromyogaphy and mechanomyographic signals were measured from the
      VM. There were no differences in neuromuscular responses pretest versus posttest
      1-RM. There were time-dependent differences between the 30% and 70% 1-RM
      protocols. The initial phase of the 30% 1-RM protocol exhibited increases in
      electromyographic-amplitude and mechanomyographic amplitude, but no changes at
      70% 1-RM. The middle phases indicated decreases in mechanomyographic amplitude at
      30% 1-RM, but increases in mechanomyographic amplitude at 70% 1-RM. The 70% 1-RM
      protocol had earlier decrease in mechanomyographic frequency than 30% 1-RM. Both
      protocols in the final phases exhibited increases in electromyographic amplitude
      and mechanomyogrpahic-amplitude, but decreases in electromyographic frequency and
      mechanomyographic frequency. Low and high intensity DCER leg extensions to
      failure have time-dependent differences in neuromuscular responses during the
      process of fatigue which suggested that motor unit activation strategies may by
      influenced by the intensity of a fatiguing workbout. Thus, examining the time
      course of changes in neuromuscular responses during a fatiguing workbout allowed
      for the identification of the time-points associated with the onset of fatigue.

PMID- 28515835
TI  - The Effect of Acute Hyperglycemia on Muscular Strength, Power and Endurance.
AB  - The purpose of this study was to elucidate the impact of acute hyperglycemia on
      skeletal muscle strength, power, and endurance. Ten male collegiate athletes (age
      21.5 +/- 1.5 years, height 186 +/- 2.03 cm, body mass 108.8 +/- 7.6 kg)
      participated in 2 testing sessions, separated by 7 days and randomized for either
      high glucose (HG) or control (C) treatment conditions. HG consumed a high glucose
      drink (2 g glucose/kg body weight) while controls consumed an isocaloric
      nutrition bar (40% protein, 30% fat, and 30% carbohydrate). Blood glucose (BC)
      levels for HG and C were tested at 0 (basal) and 30, 60, 90, and 120 minutes
      (mins) post consumption. At 30 mins post consumption, HG and C muscular strength
      was assessed by a 1RM bench press (BP) test followed by lower body power at 60
      mins via vertical jump test. Muscular endurance was examined with a 3-set-to
      failure BP test at 90 mins. HG exhibited significantly greater BC values (p<0.05)
      at the 30, 60, 90, and 120 minute time points. HG glucose area under the curve
      was significantly greater (p<0.05) than C and was positively correlated with
      %body fat, a finding that trended towards significance, r = 0.587, n= 10, p =
      0.074. There were no between group differences in maximal strength, power or
      muscular endurance. Although performance measures were unaffected by acute
      hyperglycemia, acute hyperglycemia can be induced and maintained in healthy,
      active and young subjects. Despite regular physical activity, excess body fat
      negatively impacts glucose metabolism.

PMID- 28515830
TI  - How Different Respiratory Rate Patterns affect Cardiorespiratory Variables and
      Performance.
AB  - This study aims to elucidate how respiratory rate (RR) patterns may affect
      respiratory gas exchange variables and performance during incremental intensity-
      exercise. 10 healthy young men (mean +/- SD, age: 20.7 +/- 0.5 years, height:
      174.3 +/- 5.7 cm, and body mass: 72.6 +/- 10.4 kg) performed three incremental
      tests on a cycle ergometer at three different RR (60, 45 and 30 breaths per min)
      in each trial. During the tests, tidal volume (TV), minute ventilation (VE),
      fractional content of oxygen (FeO2), fractional content of carbon dioxide
      (FeCO2), oxygen uptake (VO2), expiratory carbon dioxide (VCO2), equivalent of
      oxygen (EqO2), VE/VCO2, and respiratory exchange ratio (RER) were determinate
      breath-by-breath. Additionally, exercise time (as a performance marker) was
      measured. Statistical analyses for the results were carried out to determine
      significant differences between the three trials. VCO2, VO2, and exercise time
      did not show statistical differences in the three trials. Therefore, we concluded
      that RR affects some respiratory gas exchange variables but does not influence
      the VO2max and endurance performance.

PMID- 28515836
TI  - College Students' Knowledge of Recovery Beverage Serving Sizes.
AB  - Previous research suggests that chocolate milk may be a beneficial recovery
      beverage, yet little is known about how athletes and students training for
      careers in sports science or health-related fields interpret recommended recovery
      beverage serving sizes. This study examined college students' ability to
      correctly apply serving size recommendations for chocolate milk and protein
      powder used during post-exercise recovery and assessed usual consumption of milk
      as a recovery beverage. College students (34 women, 39 men) poured the amount of
      chocolate milk they would consume within 90 minutes after exercise unaided and
      with the use of a serving size guide. They scooped the amount of protein powder
      they would use after exercising. Participants reported consuming about 1.3+/-1.8
      glasses of milk and drinking a recovery beverage besides milk an average of
      0.95+/-1.3 times in the past three days. The majority poured less than
      recommended. Student athletes poured significantly closer to the recommendation
      than non-athletes (436+/-128 ml versus 418+/-127 ml, p=0.016) and poured
      significantly closer to the recommendation after reviewing a serving size guide
      (p=0.038). Athletes and men served themselves significantly more protein powder
      than non-athletes (13.0+/-5.6 g versus 10.3+/-5.2 g, p=0.047) and women (12.5+/
      6.0 g versus 9.8+/-4.4 g, p=0.041). Most participants reported that the serving
      size guide was easy to read and helpful. Nutrition education specific to post
      exercise recovery beverages may help students improve accuracy when interpreting
      serving size recommendations.

PMID- 28515837
TI  - Resistance Training Contribute to the Aerobic Components of an Exercise Session
      in Adults but not as Much in Older Adults.
AB  - Previous research has indicated that active adults are able to achieve moderate
      intensity as measured via heart rate during a typical resistance training (RT)
      session. The main objective was to identify if overweight adults and older adults
      can reach aerobic moderate intensity at a rate comparable to adults displaying a
      recommended body mass index. Twenty participants in each group were asked to
      visit a fitness facility twice if they self-reported doing RT for a minimum two
      days per week. At the first session baseline characteristics and maximal lifting
      capacity for each RT exercise. At the second, intensity was monitored via heart
      rate monitor during a RT exercise program composed of 10 exercises targeting
      major muscle groups. Three sets of 10 repetitions at 70% of maximal load were
      completed for each exercise. Moderate intensity was defined as a minimum of 40%
      of heart rate reserve. The proportion of time spent at moderate to vigorous
      intensity between the comparison group and the overweight adult group was not
      significantly different, with a median (25th-75th) proportion time of 82.6% (69.2
      94.6) versus 92.5% (73.3-99.1); p=.54 or an average time of 42 minutes versus 45
      minutes. The older adults group, however, spent a lower proportion of time at
      moderate to vigorous intensity compared with the comparison group, 51.5% (22.0
      86.6) or 24 minutes; p<.01 compared with the comparison group. This study
      suggests that a good proportion of time spent doing RT can contribute to an
      aerobic component of the international guidelines, and therefore reduce the
      weekly time commitment especially for men and women age below 60 years old.

PMID- 28515838
TI  - Passion for Academics and Problematic Health Behaviors.
AB  - According to the Dualistic Model of Passion (39), passion entails valuing,
      liking, and spending time on an activity. The Dualistic Model also posits two
      types of passion for activities: harmonious passion (individual voluntarily
      engages in the activity) and obsessive passion (individual is compelled to engage
      in the activity). The purpose of the present study was to examine the possible
      links between college students' passion for academic activities and problematic
      health behaviors including smoking, excessive drinking, exercise addiction,
      disordered eating, and sleepiness, which is a possible indicator of sleep
      deprivation. Participants (n = 502) completed a survey gauging passion type and
      health behaviors. Regression analyses revealed obsessive passion for academic
      activities was positively associated with scores on measures of excessive
      drinking (beta = .15, p= .008), exercise addiction (beta = .19, p<.001), and
      disordered eating (beta = .17, p < .001) but was not associated with sleep
      deprivation (beta = .07, p = .15). Harmonious passion for academic activities, in
      contrast, was negatively associated with excessive drinking behavior (beta = 
      .16, p = .002) and sleep deprivation (beta = -.13, p = .007) but was not
      associated with exercise addiction (beta = .002, p = .97) and disordered eating
      (beta = -.04, p = .37). These findings provide further support for the Dualistic
      Model of Passion. Students who are obsessively passionate about their academic
      activities are more likely to engage in poor health behaviors and, in turn, may
      experience greater negative outcomes than students who are harmoniously
      passionate about their academics.

PMID- 28515839
TI  - Hypotensive Responses of Reciprocal Supersets versus Traditional Resistance
      Training in Apparently Healthy Men.
AB  - The purpose of this study was to compare the hypotensive responses of reciprocal
      supersets (SS) versus traditional training (TRAD) methods. Thirteen men with at
      least five years of recreational experience in resistance training (RT)
      volunteered for the study. When completing the TRAD protocol, participants
      performed the following exercises separately in sequence: chest press (CP), low
      row (LR), leg extension (LE), leg curl (LC), pull down (PD), and shoulder press
      (SP). The SS method required participants to complete the same exercises as in
      the TRAD protocol, but exercises were coupled such that muscles sequentially
      served both as an agonist for lift one and then antagonist for lift two and vice
      versa. Exercise order used was CP and LR, LE and LC, and PD and SP with 10
      repetition maximum loads. Blood pressure (BP) was measured before and for every
      10 minutes for one hour after training. There was significantly more total work
      (TW) done in the TRAD condition compared to SS. Post exercise hypotension was
      evident only after the TRAD session at minutes 30 and 40 for systolic BP.
      Significant differences between the TRAD and SS methods were found at 20 minutes,
      30 minutes, and 40 minutes for systolic BP. There was no significant two-way
      interaction for group * time for diastolic BP. There was a significant two-way
      interaction for group * time for mean arterial pressure. Significant reductions
      for mean arterial pressure (MAP) occurred only in the TRAD method after 30 to 40
      minutes compared to the baseline values. Therefore, a TRAD RT method was
      sufficient to cause a hypotensive effect after the training session whereas the
      SS method did not reveal significant decreases in BP after the session. However,
      these findings are important to elucidate concerns regarding the post-exercise
      hypotension after RT and showed that TW might be the key to promote these changes
      because the volume of training was shown to be an important training variable to
      manipulate and might be associated with BP hypotension after RT.

PMID- 28515840
TI  - Self-optimization of Stride Length Among Experienced and Inexperienced Runners.
AB  - Experienced runners appear to naturally select a stride length which is optimal
      for minimizing oxygen uptake. However, whether this ability is naturally built
      into the human body or whether it is learned through experience has not been
      previously tested. This study investigated whether inexperienced runners are as
      capable as experienced runners of self-optimizing stride length to minimize
      oxygen uptake. Thirty-three subjects (nineteen experienced and fourteen
      inexperienced) ran for twenty-minutes while preferred and economical stride
      lengths were measured. A t-test checked for differences between the experienced
      and inexperienced groups in the percent increase of oxygen uptake due to not
      running at the most economical stride length. No difference was found between
      groups with the increase in oxygen uptake due to not being optimized (p=0.47).
      The average percent increase in oxygen uptake above the most economical for
      inexperienced and experienced runners was 1.8% and 1.2% respectively. We
      concluded that inexperienced and experienced runners are equally capable of
      matching preferred stride length to economical stride length, thus athletes and
      coaches do not need to alter runner's stride length when economy is the main
      concern.

PMID- 28515842
TI  - Casein Protein Supplementation in Trained Men and Women: Morning versus Evening.
AB  - The purpose of this investigation was to determine the effects of casein
      supplementation (54 grams) in the morning (Casein-MOR) or evening (Casein-EVE)
      (90 minutes or less prior to sleep) on measures of body composition and exercise
      performance in trained men and women. Twenty-six healthy men and women who had
      been training regularly for greater than 12 months completed this 8-week study
      (mean+/-SD; Casein-MOR group [n=14, seven male, seven female]: 30.0+/-8.2 yr;
      170.7+/-9.5 cm; 70.9+/-13.9 kg. Casein-EVE group [n=12, nine male, three female]:
      28.9+/-9.5 yr; 172.9+/-7.3 cm; 72.6+/-10.9 kg). Subjects in each group
      supplemented with casein protein (54 grams) either in the morning (prior to
      12:00pm) or evening (~90 minutes or less prior to sleep). Subjects were advised
      to not significantly alter their training program as well as to keep a diary of
      their workouts. Body composition was assessed via the Bod Pod(r). In addition,
      subjects provided dietary self-reports via MyFitnessPal(r). Approximately 24
      daily dietary self-reports were provided from each subject that self-monitored
      their diet. The investigators monitored their diet throughout the study. Both the
      Casein-MOR and Casein-EVE groups consumed significantly more protein (post versus
      pre; p<0.05); however, there were no between-group differences regarding protein
      intake. Furthermore, there were no within- or between-group differences for any
      other measure. In trained subjects who did not significantly alter their training
      program, the addition of 54 grams of casein protein in the morning or evening had
      no significant effects on body composition. Furthermore, the additional
      consumption of protein calories did not result in an increase in fat mass despite
      the fact that exercise volume did not change.

PMID- 28515841
TI  - Demands of Simulated Commuting Using an Electrically Assisted Bicycle.
AB  - The American College of Sports Medicine (ACSM) recommends adults participate in
      weekly aerobic activity for a minimum of 30 minutes moderate intensity exercise 5
      days per week or 20 minutes of vigorous activity 3 days per week. The
      electrically assisted bicycle may help individuals achieve the ACSM's aerobic
      recommendations and introduce inactive individuals to physical activity. To
      compare the physiological requirements of riding a bicycle with electric pedal
      assist versus non-assist among healthy active young adults. 6 males and 6 females
      completed two randomized cycling trials using electric pedal assist (PAB) and non
      assist (NON). Cycling trials were completed over a 3.54 km course with varying
      terrain. Time to completion was faster in the PAB (12.5 +/- 0.3 min) than the NON
      (13.8 +/- 0.3 min, p=0.01). Rating of Perceived Exertion (RPE) was lower in the
      PAB (12.0 +/- 0.4) than the NON (14.8 +/- 0.5, p < 0.001). There was no
      difference in mean VO2 between PAB (2.3 +/- 0.1 L.min-1) and NON (2.5 +/- 0.1
      L.min-1, p=0.45). There was no difference in mean power output when comparing PAB
      (115 +/- 11 Watts) to NON (128 +/- 11 Watts, p=0.38). There was no difference in
      heart rate between PAB (147 +/- 5 bpm) and NON (149 +/- 5 bpm, p=0.77).
      Recreationally active younger (college age) individuals may self-select a similar
      physiological intensity of physical activity regardless of mechanical assistance,
      resulting in quicker completion of a commuting task with PAB. Both the PAB and
      NON exercise bouts met ACSM criteria for vigorous exercise.

PMID- 28515844
TI  - Role of circulating microRNAs in liver diseases.
AB  - MicroRNAs (miRNAs) are small RNAs regulate gene expression by inhibiting the
      turnover of their target mRNAs. In the last years, it became apparent that miRNAs
      are released into the circulation and circulating miRNAs emerged as a new class
      of biomarkers for various diseases. In this review we summarize available data on
      the role of circulating miRNAs in the context of acute and chronic liver diseases
      including hepatocellular and cholangiocellular carcinoma. Data from animal models
      are compared to human data and current challenges in the field of miRNAs research
      are discussed.

PMID- 28515845
TI  - Diagnosis of morbid obesity may not impact healthcare utilization for orthotopic
      liver transplantation: A propensity matched study.
AB  - AIM: To study mortality, length of stay, and total charges in morbidly obese
      adults during index hospitalization for orthotopic liver transplantation.
      METHODS: The Nationwide Inpatient Sample was queried to obtain demographics,
      healthcare utilization, post orthotopic liver transplantation (OLT)
      complications, and short term outcomes of OLT performed from 2003 to 2011 (n =
      46509). We divided patients into those with [body mass index (BMI) >= 40] and
      without (BMI < 40) morbid obesity. Multivariable logistic regression analysis was
      performed to characterize differences in in-hospital mortality, length of stay
      (LOS), and charges for OLT between patients with and without morbid obesity after
      adjusting for significant confounders. Additionally, propensity matching was
      performed to further validate the results. RESULTS: Of the 46509 patients who
      underwent OLT during the study period, 818 (1.8%) were morbidly obese. Morbidly
      obese recipients were more likely to be female (46.8% vs 33.4%, P = 0.002),
      Caucasian (75.2% vs 67.8%, P = 0.002), in the low national income quartile (32.3%
      vs 22.5%, P = 0.04), and have >= 3 comorbidities (modified Elixhauser index;
      83.9% vs 45.0%, P < 0.001). Morbidly obese patient also had an increase in
      procedure related hemorrhage (P = 0.028) and respiratory complications (P =
      0.043). Multivariate and propensity matched analysis showed no difference in
      mortality (OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS (beta: -4.44; 95%CI: -9.93,
      1.05, P = 0.11) and charges for transplantation (beta: $15693; 95%CI: -51622
      83008, P = 0.64) between the two groups. Morbidly obese patients were more likely
      to have transplants on weekdays (81.7%) as compared to those without morbid
      obesity (75.4%, P = 0.029). CONCLUSION: Morbid obesity may not impact in-hospital
      mortality and health care utilization in OLT recipients. However, morbidly obese
      patients may be selected after careful assessment of co-morbidities.

PMID- 28515846
TI  - Passive expansion of sub-maximally dilated transjugular intrahepatic
      portosystemic shunts and assessment of clinical outcomes.
AB  - AIM: To assess for passive expansion of sub-maximally dilated transjugular
      intrahepatic portosystemic shunts (TIPS) and compare outcomes with maximally
      dilated TIPS. METHODS: Polytetrafluoroethylene covered TIPS (Viatorr) from July
      2002 to December 2013 were retrospectively reviewed at two hospitals in a single
      institution. Two hundred and thirty patients had TIPS maximally dilated to 10 mm
      (mTIPS), while 43 patients who were at increased risk for hepatic encephalopathy
      (HE), based on clinical evaluation or low pre-TIPS portosystemic gradient (PSG),
      had 10 mm TIPS sub-maximally dilated to 8 mm (smTIPS). Group characteristics
      (age, gender, Model for End-Stage Liver Disease score, post-TIPS PSG and clinical
      outcomes were compared between groups, including clinical success (ascites or
      varices), primary patency, primary assisted patency, and severe post-TIPS HE. A
      subset of fourteen patients with smTIPS underwent follow-up computed tomography
      imaging after TIPS creation, and were grouped based on time of imaging (< 6 mo
      and > 6 mo). Change in diameter and cross-sectional area were measured with 3D
      imaging software to evaluate for passive expansion. RESULTS: Patient
      characteristics were similar between the smTIPS and mTIPS groups, except for pre
      TIPS portosystemic gradient, which was lower in the smTIPS group (19.4 mmHg +/-
      6.8 vs 22.4 mmHg +/- 7.1, P = 0.01). Primary patency and primary assisted patency
      between smTIPS and mTIPS was not significantly different (P = 0.64 and 0.55,
      respectively). Four of the 55 patients (7%) with smTIPS required TIPS reduction
      for severe refractory HE, while this occurred in 6 of the 218 patients (3%) with
      mTIPS (P = 0.12). For the 14 patients with follow-up computed tomography (CT)
      imaging, the median imaging follow-up was 373 d. There was an increase in median
      TIPS diameter, median percent diameter change, median area, and median percent
      area change in patients with CT follow-up greater than 6 mo after TIPS placement
      compared to follow-up within 6 mo (8.45 mm, 5.58%, 56.04 mm2, and 11.48%,
      respectively, P = 0.01). CONCLUSION: Passive expansion of smTIPS does occur but
      clinical outcomes of smTIPS and mTIPS were similar. Sub-maximal dilation can
      prevent complications related to over-shunting in select patients.

PMID- 28515665
TI  - Measurement of the WZ production cross section in pp collisions at [Formula: see
      text] and 8[Formula: see text] and search for anomalous triple gauge couplings at
      [Formula: see text].
AB  - The WZ production cross section is measured by the CMS experiment at the CERN LHC
      in proton-proton collision data samples corresponding to integrated luminosities
      of 4.9[Formula: see text] collected at [Formula: see text], and 19.6[Formula: see
      text] at [Formula: see text]. The measurements are performed using the fully
      leptonic WZ decay modes with electrons and muons in the final state. The measured
      cross sections for [Formula: see text] are [Formula: see text] [Formula: see
      text] and [Formula: see text] [Formula: see text]. Differential cross sections
      with respect to the [Formula: see text] boson [Formula: see text], the leading
      jet [Formula: see text], and the number of jets are obtained using the [Formula:
      see text] data. The results are consistent with standard model predictions and
      constraints on anomalous triple gauge couplings are obtained.

PMID- 28515848
TI  - Coronary artery disease detection - limitations of stress testing in left
      ventricular dysfunction.
AB  - Incidental diagnosis of left ventricular systolic dysfunction (LVD) is common in
      clinical practice. The prevalence of asymptomatic LVD (Ejection Fraction, EF <
      50%) is 6.0% in men and 0.8% in women and is twice as common as symptomatic LVD.
      The timely and definitive exclusion of an ischemic etiology is central to
      optimizing care and reducing mortality in LVD. Advances in cardiovascular imaging
      provide many options for imaging of patients with left ventricular dysfunction.
      Clinician experience, patient endurance, imaging modality characteristics, cost
      and safety determine the choice of testing. In this review, we have compared the
      diagnostic utility of established tests - nuclear and echocardiographic stress
      testing with newer techniques like coronary computerized tomography and cardiac
      magnetic resonance imaging and highlight their inherent limitations in patients
      with underlying left ventricular dysfunction.

PMID- 28515847
TI  - Pacemaker recycling: A notion whose time has come.
AB  - The purpose of this paper is to summarize the need, feasibility, safety,
      legality, and ethical perspectives of pacemaker reutilization in low- and middle
      income countries (LMICs). It will also describe, in-depth, Project My Heart Your
      Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the
      discussion points in this paper is a collection of 14 publications produced by
      the research team at the University of Michigan and its collaborative partners.
      The need for pacemaker reutilization in LMICs is evident. Numerous studies show
      that the concept of pacemaker reutilization in LMICs is feasible. Infection and
      device malfunction are the main concerns in regard to pacemaker reutilization,
      yet many studies have shown that pacemaker reuse is not associated with increased
      infection risk or higher mortality compared with new device implantation. Under
      the right circumstances, the ethical and legal bases for pacemaker reutilization
      are supported. PMHYH is a proof of concept pacemaker donation initiative that has
      allowed funeral home and crematory directors to send explanted devices to an
      academic center for evaluation and re-sterilization before donation to
      underserved patients in LMICs. The time is now to pursue large-scale studies and
      trials of pacemaker reuse for the betterment of society. PMHYH is leading the way
      in the effort and is poised to conduct a prospective randomized, non-inferiority,
      multicenter study to confirm the clinical efficacy and safety of pacemaker reuse,
      for clinical and legal support.

PMID- 28515843
TI  - Emerging concepts in alcoholic hepatitis.
AB  - Severe alcoholic hepatitis is implicated as a costly, worldwide public health
      issue with high morbidity and mortality. The one-month survival for severe
      alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from
      alcohol is the recommended first-line treatment. Although corticosteroids remain
      as the current evidence based option for selected patients with discriminant
      function > 32, improvement of short-term survival rate may be the only benefit.
      Identification of individuals with risk factors for the development of severe
      alcoholic hepatitis may provide insight to the diverse clinical spectrum and
      prognosis of the disease. The understanding of the complex pathophysiologic
      processes of alcoholic hepatitis is the key to elucidating new therapeutic
      treatments. Newer research describes the use of gut microbiota modification,
      immune modulation, stimulation of liver regeneration, caspase inhibitors,
      farnesoid X receptors, and the extracorporeal liver assist device to aid in
      hepatocellular recovery. Liver transplantation can be considered as the last
      medical option for patients failing conventional medical interventions. Although
      the preliminary data is promising in patients with low risk of recividism,
      controversy remains due to organ scarcity. This review article comprehensively
      summarizes the epidemiology, pathophysiology, risk factors, and prognostic
      indicators of severe alcoholic hepatitis with a focus on the current and emerging
      therapeutics.

PMID- 28515849
TI  - Feature tracking cardiac magnetic resonance imaging: A review of a novel non
      invasive cardiac imaging technique.
AB  - Cardiovascular disease is a leading cause of morbidity and mortality globally.
      Early diagnostic markers are gaining popularity for better patient care disease
      outcomes. There is an increasing interest in noninvasive cardiac imaging
      biomarkers to diagnose subclinical cardiac disease. Feature tracking cardiac
      magnetic resonance imaging is a novel post-processing technique that is
      increasingly being employed to assess global and regional myocardial function.
      This technique has numerous applications in structural and functional
      diagnostics. It has been validated in multiple studies, although there is still a
      long way to go for it to become routine standard of care.

PMID- 28515850
TI  - Dissection of Z-disc myopalladin gene network involved in the development of
      restrictive cardiomyopathy using system genetics approach.
AB  - AIM: To investigate the regulation of Myopalladin (Mypn) and identify its gene
      network involved in restrictive cardiomyopathy (RCM). METHODS: Gene expression
      values were measured in the heart of a large family of BXD recombinant inbred
      (RI) mice derived from C57BL/6J and DBA/2J. The proteomics data were collected
      from Mypn knock-in and knock-out mice. Expression quantitative trait locus (eQTL)
      mapping methods and gene enrichment analysis were used to identify Mypn
      regulation, gene pathway and co-expression networks. RESULTS: A wide range of
      variation was found in expression of Mypn among BXD strains. We identified
      upstream genetic loci at chromosome 1 and 5 that modulate the expression of Mypn.
      Candidate genes within these loci include Ncoa2, Vcpip1, Sgk3, and Lgi2. We also
      identified 15 sarcomeric genes interacting with Mypn and constructed the gene
      network. Two novel members of this network (Syne1 and Myom1) have been confirmed
      at the protein level. Several members in this network are already known to relate
      to cardiomyopathy with some novel genes candidates that could be involved in RCM.
      CONCLUSION: Using systematic genetics approach, we constructed Mypn co-expression
      networks that define the biological process categories within which similarly
      regulated genes function. Through this strategy we have found several novel genes
      that interact with Mypn that may play an important role in the development of
      RCM.

PMID- 28515852
TI  - Bilateral vs unilateral internal mammary revascularization in patients with left
      ventricular dysfunction.
AB  - AIM: To investigate the survival benefit of bilateral internal mammary artery
      (BIMA) grafts in patients with left ventricular dysfunction. METHODS: Between
      1996 and 2009, we performed elective, isolated, primary, multiple cardiac
      arterial bypass grafting in 430 consecutive patients with left ventricular
      ejection fraction <= 40%. The early and long-term results were compared between
      167 patients undergoing BIMA grafting and 263 patients using left internal
      mammary artery (LIMA)-saphenous venous grafting (SVG). RESULTS: The mean age of
      the overall population was 60.1 +/- 15 years. In-hospital mortality was not
      different between the two groups (7.8% vs 10.3%, P = 0.49). Early postoperative
      morbidity included myocardial infarction (4.2% vs 3.8%, P = 0.80), stroke (1.2%
      vs 3.8%, P = 0.14), and mediastinitis (5.3% vs 2.3%, P = 0.11). At 8-year follow
      up, Kaplan-Meier-estimated survival (74.2% vs 58.9%, P = 0.02) and Kaplan-Meier
      estimated event-free survival (all cause deaths, myocardial infarction, stroke,
      target vessel revascularization, heart failure) (61.7% and 41.1%, P < 0.01) were
      significantly higher in the BIMA group compared with the LIMA-SVG group in
      univariate analysis. The propensity score matching analysis confirmed that BIMA
      grafting is a safe revascularization procedure but there was no long term
      survival (P = 0.40) and event-free survival (P = 0.13) in comparison with LIMA
      SVG use. CONCLUSION: Our longitudinal analysis suggests that BIMA grafting can be
      performed with acceptable perioperative mortality in patients with left
      ventricular dysfunction.

PMID- 28515851
TI  - Blood conservation pediatric cardiac surgery in all ages and complexity levels.
AB  - AIM: To demonstrate the feasibility of blood conservation methods and practice
      across all ages and risk categories in congenital cardiac surgery. METHODS: We
      retrospectively analyzed a collected database of 356 patients who underwent
      cardiac surgery using cardiopulmonary bypass (CPB) from 2010-2015. The patients
      were grouped into blood conservation (n = 138) and non-conservation (n = 218)
      groups and sub-grouped based on their ages and procedural complexity scores.
      RESULTS: There were no statistical differences in gender, weight, pre-operative
      and pre-CPB hematocrit levels in both groups. Despite equivalent hematocrit
      levels during and after CPB for both groups, there was significantly less
      operative homologous blood utilized in blood conservation group across all ages
      and complexity levels. CONCLUSION: Blood conservation surgery can be performed in
      congenital patients needing cardiac surgery in all age groups and complexity
      categories. The above findings in addition to attendant risks and side effects of
      blood transfusion and the rising cost of safer blood products justify blood
      conservation in congenital cardiac surgery.

PMID- 28515856
TI  - Inter-ethnic marriages and severity of coronary artery disease: A multicenter
      study of Arabian Gulf States.
AB  - AIM: To assess the association of inter-ethnic vs intra-ethnic marriage with
      severity of coronary artery disease (CAD) in men undergoing angiography. METHODS:
      We conducted a prospective multicenter, multi-ethnic, cross sectional
      observational study at five hospitals in Saudi Arabia and the United Arab
      Emirates, in which we used logistic regression analysis with and without
      adjustment for baseline differences. RESULTS: Data were collected for 1068
      enrolled patients undergoing coronary angiography for clinical indications during
      the period of April 1st, 2013 to March 30th, 2014. Ethnicities of spouses were
      available only for male patients. Of those enrolled, 687 were married men and
      constituted the cohort for the present analysis. Intra-ethnic marriages were
      reported in 70% and inter-ethnic marriages in 30%. After adjusting for baseline
      differences, inter-ethnic marriage was associated with lower odds of having
      significant CAD [adjusted odds ratio 0.52 (95%CI: 0.33, 0.81)] or multi-vessel
      disease (MVD) [adjusted odds ratio 0.57 (95%CI: 0.37, 0.86)]. The adjusted
      association with left main disease showed a similar trend, but was not
      statistically significant [adjusted odds ratio 0.74 (95%CI: 0.41, 1.32)]. The
      association between inter-ethnic marriage and the presence of significant CAD and
      MVD was not modified by number of concurrent wives (P interaction > 0.05 for
      both). CONCLUSION: Among married men undergoing coronary angiography, inter
      ethnic, as compared to intra-ethnic, marriage is associated with lower odds of
      significant CAD and MVD.

PMID- 28515853
TI  - QT prolongation is associated with increased mortality in end stage liver
      disease.
AB  - AIM: To determine the prevalence of QT prolongation in a large series of end
      stage liver disease (ESLD) patients and its association to clinical variables and
      mortality. METHODS: The QT interval was measured and corrected for heart rate for
      each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT
      > 470 ms for females. Multiple clinical variables were evaluated including sex,
      age, serum sodium, international normalized ratio, creatinine, total bilirubin,
      beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology
      of liver disease. RESULTS: Among 406 ESLD patients analyzed, 207 (51.0%) had QT
      prolongation. The only clinical variable associated with QT prolongation was male
      gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187
      patients (46.1%) died. QT prolongation was a significant independent predictor of
      mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was
      also associated with viral etiology of ESLD, elevated MELD score and its
      components (P < 0.05 for all). No significant reversibility in the QT interval
      was seen after liver transplantation. CONCLUSION: QT prolongation was commonly
      encountered in an ESLD population, especially in males, and served as a strong
      independent marker for increased mortality in ESLD patients.

PMID- 28515858
TI  - Three-dimensional optical coherence tomography reconstruction of bifurcation
      stenting using the Szabo anchor-wire technique.
AB  - Ostial lesions present unique challenges for percutaneous coronary intervention
      (PCI). These lesions are often more calcified, fibrotic, rigid, and more prone to
      elastic recoil. Intervention on these lesions is associated with higher
      procedural complications and higher rates of restenosis. Ostial lesions require
      precise stent placement in the ostium with the absence of side branch compromise.
      Accurate stent placement in the ostium without side branch compromise is
      difficult to accomplish with angiography alone. The Szabo technique uses two
      coronary guidewires for the correct placement in the aorto-ostial or bifurcation
      lesion. One guidewire is passed through the final cell of the stent strut and
      acts as the anchor wire. It helps to prevent migration of the stent beyond the
      ostium and facilitates the precise stenting at the ostium. This technique has
      several advantages including less reliance on angiography, lower rates of stent
      malposition and lower rates of incomplete stent coverage. Potential disadvantages
      include stent distortion and dislodgement from stent manipulation. We describe
      two cases of successful PCI to bifurcation lesions using the Szabo technique and
      confirmation of correct placement in the ostium with optical coherence
      tomography.

PMID- 28515857
TI  - Contrast use in relation to the arterial access site for percutaneous coronary
      intervention: A comprehensive meta-analysis of randomized trials.
AB  - AIM: To compare the amount of contrast used during percutaneous coronary
      intervention (PCI) via trans-radial access (TRA) vs trans-femoral access (TFA).
      METHODS: Scientific databases and websites were searched
      for:randomizedcontrolledtrials (RCTs). Data were extracted by two independent
      reviewers and was summarized as the weighted mean difference (WMD) of contrast
      used with a 95%CI using a random-effects model. RESULTS: The meta-analysis
      included 13 RCTs with a total of 3165 patients. There was no difference between
      the two strategies in the amount of contrast used (WMD = - 0.65 mL, 95%CI: -10.94
      9.46 mL; P = 0.901). CONCLUSION: This meta-analysis shows that in patients
      undergoing PCI, the amount of contrast volume used was not different between TRA
      and TFA.

PMID- 28515855
TI  - Speckle tracking echocardiography to assess regional ventricular function in
      patients with apical hypertrophic cardiomyopathy.
AB  - AIM: To explore regional systolic strain of midwall and endocardial segments
      using speckle tracking echocardiography in patients with apical hypertrophic
      cardiomyopathy (HCM). METHODS: We prospectively assessed 20 patients (mean age 53
      +/- 16 years, range: 18-81 years, 10 were male), with apical HCM. We measured
      global longitudinal peak systolic strain (GLPSS) in the midwall and endocardium
      of the left ventricle. RESULTS: The diastolic thickness of the 4 apical segments
      was 16.25 +/- 2.75 mm. All patients had a normal global systolic function with a
      fractional shortening of 50% +/- 8%. In spite of supernormal left ventricular
      (LV) systolic function, midwall GLPSS was decreased in all patients, more in the
      apical (-7.3% +/- -8.8%) than in basal segments (-15.5% +/- -6.93%), while
      endocardial GLPPS was significantly greater and reached normal values (apical: 
      22.8% +/- -7.8%, basal: -17.9% +/- -7.5%). CONCLUSION: This study shows that two
      dimensional strain was decreased mainly confined to the mesocardium, while
      endocardium myocardial deformation was preserved in HCM and allowed to identify
      subclinical LV dysfunction. This transmural heterogeneity in systolic strain had
      not been previously described in HCM and could be explained by the distribution
      of myofibrillar disarray in deep myocardial areas. The clinical application of
      this novel finding may help further understanding of the pathophysiology of HCM.

PMID- 28515859
TI  - Conservative management of aortic root rupture complicated with cardiac tamponade
      following transcatheter aortic valve implantation.
AB  - Aortic root rupture and cardiac tamponade during transcatheter aortic valve
      implantation is a frightening complication with high mortality rate. A
      conservative management of this complication could represent an initial strategy,
      especially in high-risk patients, to avoid emergent cardiac surgery. This
      conservative management includes: Immediate detection of pericardial effusion by
      echocardiography, a fast instauration of pericardial drainage, auto-transfusion
      and anticoagulation reversal. We describe two cases of patients who suffered this
      complication and were treated successfully with this initial approach.

PMID- 28515854
TI  - Determinants of percutaneous coronary intervention success in repeat chronic
      total occlusion procedures following an initial failed attempt.
AB  - AIM: To investigate the rates and determinants of success of repeat percutaneous
      coronary intervention (PCI) following an initial failed attempt at recanalising
      the chronic total occlusions (CTO) percutaneously. METHODS: In 445 consecutive
      first attempt CTO-PCI procedures in our institution, procedural failure occurred
      in 149 (33.5%). Sixty-four re-PCI procedures were performed in 58 patients (39%)
      all had a single CTO. Procedural and outcome data in the re-PCI population was
      entered into the institutional database. A retrospective analysis of clinical,
      angiographic and procedural data was performed. RESULTS: Procedural success was
      achieved in 41 (64%) procedures. Univariate analysis of clinical and angiographic
      characteristics showed that re-PCI success was associated with intravascular
      ultrasound (IVUS) guidance (19.5% vs 0%, P = 0.042), while failure was associated
      with severe calcification (30.4% vs 9.7%, P = 0.047) and a JCTO score > 3 (56.5%
      vs 17.1% P = 0.003). Following multiple regression analysis the degree of lesion
      complexity (J-CTO score > 3), IVUS use, involvement of an experienced CTO
      operator and LAD CTO location were significant predictors of successful re-PCI.
      Overall the complication rate was low, with the only MACCE two periprocedural
      MI's neither of which required intervention. CONCLUSION: Re-PCI substantially
      increases the overall success rate of CTO revascularization. Predictors of re-PCI
      success included the use of IVUS, the involvement of an experienced CTO operator
      in the repeat attempt and the location of the CTO.

PMID- 28515860
TI  - Cardiotoxicity occurred in aged C57BL/6nia mice given a formulation containing
      poloxamer 407 hydrogel.

PMID- 28515861
TI  - The emerging role of geropathology in preclinical aging studies.

PMID- 28515862
TI  - Guidelines for collection and processing of lungs from aged mice for histological
      studies.
AB  - Pulmonary inflammation and the development of spontaneous lung tumors are
      important age-related lesions in mice. Therefore, gross and histological
      examination of the respiratory system is a critical component of geropathology
      research studies for translating surrogate endpoints to clinical aging studies.
      Collection, trimming, and processing of lung tissue from aged mice require a high
      quality sequential process since aged mice are irreplaceable resource-intensive
      animal models. This protocol provides a basic technique that provides excellent
      sections for histological evaluation of the respiratory system of old mice
      suitable for most research applications. The points of emphasis are infusing the
      lungs at necropsy with formalin through the airways to prevent atelectasis
      artifacts that can preclude accurate histological evaluation, and embedding of
      anatomically oriented in toto lung lobes to allow for complete and thorough
      evaluation of all lung regions.

PMID- 28515863
TI  - Structural Segmentation of Toru Takemitsu's Piece, Itinerant, by Advanced Level
      Music Graduate Students.
AB  - This work attempts to study the way higher music graduate students segment a
      contemporary music work, Itinerant, and to understand the influence of musical
      feature on segmentation. It attempts to test the theory stating that saliences
      contribute to organising the music surface. The 42 students listened to the work
      several times and, in real time, they were requested to indicate the places on
      the score where they perceived structural boundaries. This work is characterised
      by its linearity, which could hinder identification of saliences and thereby, the
      establishment of structural boundaries. The participants show stability in the
      points of segmentation chosen. The results show significant coincidences among
      the participants in strategic places of the work, which leads us to conclude, in
      line with other researches, although in a work with different characteristics,
      that listeners can find a structural organisation in contemporary music that
      could allow them to understand it.

PMID- 28515864
TI  - The Planispheric Optic Array.
AB  - The "planispheric optic array" is a full-horizon Mercator projection of the optic
      array. Such pictures of the environment are coming in common use with the
      availability of cheap full-view cameras of reasonable quality. This introduces
      the question of whether the public will actually profit from such pictorial
      information in terms of an understanding of the spatial layout of the depicted
      scene. Test images include four persons located at the corners of a square
      centered at the camera. The persons point at each other in various combinations.
      Participants in the experiment judge who is pointing at whom in a number of such
      photographs. It is found that certain very systematic and huge errors are the
      rule, indicating that naive viewers are quite unable to parse such planispheric
      representations.

PMID- 28515865
TI  - Innocent Body-Shadow Mimics Physical Body.
AB  - The paradigm of the rubber hand illusion was applied to a shadow to determine
      whether the body-shadow is a good candidate for the alternative belonging to our
      body. Three kinds of shadows, a physical hand, a hand-shaped cloth, and a
      rectangle cloth, were tested for this purpose. The questionnaire results showed
      that both anatomical similarity and visuo-proprioception correlation were
      effective in enhancing illusory ownership of the shadow. According to the
      proprioceptive drift measurement, whether the shadow purely originated from the
      physical body was a critical factor in yielding the significantly positive drift.
      Thus, results demonstrated that the shadow can distort illusory ownership with
      the rubber hand illusion paradigm, but the proprioception was clearly distorted
      only when the body-shadow was purely applied. This implies the presence of
      special cognitive processing to discriminate the self-body shadow from the
      others.

PMID- 28515866
TI  - Effect of Different Display Types on Vection and Its Interaction With Motion
      Direction and Field Dependence.
AB  - Illusory self-motion (vection) can be generated by visual stimulation. The
      purpose of the present study was to compare behavioral vection measures including
      intensity ratings, duration, and onset time across different visual display
      types. Participants were exposed to a pattern of alternating black-and-white
      horizontal or vertical bars that moved either in vertical or horizontal
      direction, respectively. Stimuli were presented on four types of displays in
      randomized order: (a) large field of view dome projection, (b) combination of
      three computer screens, (c) single computer screen, (d) large field of view flat
      projection screen. A Computer Rod and Frame Test was used to measure field
      dependence, a cognitive style indicating the person's tendency to rely on
      external cues (i.e., field dependent) or internal cues (i.e., field independent)
      with respect to the perception of one's body position in space. Results revealed
      that all four displays successfully generated at least moderately strong vection.
      However, shortest vection onset, longest vection duration, and strongest vection
      intensity showed for the dome projection and the combination of three screens.
      This effect was further pronounced in field independent participants, indicating
      that field dependence can alter vection.

PMID- 28515867
TI  - The evolution of the major histocompatibility complex in upstream versus
      downstream river populations of the longnose dace.
AB  - Populations in upstream versus downstream river locations can be exposed to
      vastly different environmental and ecological conditions and can thus harbor
      different genetic resources due to selection and neutral processes. An
      interesting question is how upstream-downstream directionality in rivers affects
      the evolution of immune response genes. We used next-generation amplicon
      sequencing to identify eight alleles of the major histocompatibility complex
      (MHC) class II beta exon 2 in the cyprinid longnose dace (Rhinichthys cataractae)
      from three rivers in Alberta, upstream and downstream of municipal and
      agricultural areas along contaminant gradients. We used these data to test for
      directional and balancing selection on the MHC. We also genotyped microsatellite
      loci to examine neutral population processes in this system. We found evidence
      for balancing selection on the MHC in the form of increased nonsynonymous
      variation relative to neutral expectations, and selection occurred at more amino
      acid residues upstream than downstream in two rivers. We found this pattern
      despite no population structure or isolation by distance, based on microsatellite
      data, at these sites. Overall, our results suggest that MHC evolution is driven
      by upstream-downstream directionality in fish inhabiting this system.

PMID- 28515869
TI  - Implications of guppy (Poecilia reticulata) life-history phenotype for mosquito
      control.
AB  - Guppies (Poecilia reticulata) are frequently introduced to both natural and
      artificial water bodies as a mosquito control. Laboratory studies have
      demonstrated that guppies can consume large numbers of larval mosquitoes. Our
      study investigates how intraspecific variability in guppy phenotype affects their
      importance as a mosquito biocontrol and how habitat conditions (natural ponds vs.
      water storage containers) may influence insect biomass and guppy feeding. Using a
      blocked experimental design, we established stream-side mesocosm ponds with half
      receiving gravel substrate to simulate pond-bottom habitat. To provide realistic
      diet choices and insect abundances, we allowed the mesocosms to colonize
      naturally with aquatic insect larvae for 1 month before introducing guppies. We
      tested two distinct guppy phenotypes (from high- and low-predation streams)
      alongside fish-free controls. After 1 month, we measured insect biomass in the
      mesocosms and examined guppy gut contents to document direct predation. While
      overall insect biomass was not significantly different across the three fish
      treatments, we observed a significant reduction in mosquito biomass in fish
      treatments compared to fish-free controls, as well as intraspecific differences
      in feeding. Overall insect biomass was significantly higher in mesocosms without
      gravel, while habitat condition had no effect on mosquito biomass. As guppy
      phenotype responds to changes in their environments, it is an important
      consideration for biocontrol policy to anticipate potential ecosystem effects. We
      close by relating our findings to other studies and by discussing the
      implications and potential risks of using guppies to control mosquitoes.

PMID- 28515868
TI  - Postglacial recolonization shaped the genetic diversity of the winter moth
      (Operophtera brumata) in Europe.
AB  - Changes in climate conditions, particularly during the Quaternary climatic
      oscillations, have long been recognized to be important for shaping patterns of
      species diversity. For species residing in the western Palearctic, two commonly
      observed genetic patterns resulting from these cycles are as follows: (1) that
      the numbers and distributions of genetic lineages correspond with the use of
      geographically distinct glacial refugia and (2) that southern populations are
      generally more diverse than northern populations (the "southern richness,
      northern purity" paradigm). To determine whether these patterns hold true for the
      widespread pest species the winter moth (Operophtera brumata), we genotyped 699
      individual winter moths collected from 15 Eurasian countries with 24 polymorphic
      microsatellite loci. We find strong evidence for the presence of two major
      genetic clusters that diverged ~18 to ~22 ka, with evidence that secondary
      contact (i.e., hybridization) resumed ~ 5 ka along a well-established hybrid zone
      in Central Europe. This pattern supports the hypothesis that contemporary
      populations descend from populations that resided in distinct glacial refugia.
      However, unlike many previous studies of postglacial recolonization, we found no
      evidence for the "southern richness, northern purity" paradigm. We also find
      evidence for ongoing gene flow between populations in adjacent Eurasian
      countries, suggesting that long-distance dispersal plays an important part in
      shaping winter moth genetic diversity. In addition, we find that this gene flow
      is predominantly in a west-to-east direction, suggesting that recently debated
      reports of cyclical outbreaks of winter moth spreading from east to west across
      Europe are not the result of dispersal.

PMID- 28515870
TI  - Behavioral responses to encounter of fishing boats in wandering albatrosses.
AB  - Animals are attracted to human food subsidies worldwide. The behavioral response
      of individuals to these resources is rarely described in detail, beyond chances
      of encounters. Seabirds for instance scavenge in large numbers at fishing boats,
      triggering crucial conservation issues, but how the response to boats varies
      across encounters is poorly known. Here we examine the behavioral response of
      wandering albatrosses (Diomedea exulans), equipped with GPS tags, to longline
      fishing boats operating near their colony for which we had access to vessel
      monitoring system data. We distinguish between encounters (flying within 30 km of
      a boat) and attendance behavior (sitting on the sea within 3 km of a boat), and
      examine factors affecting each. In particular, we test hypotheses that the
      response to encountered boats should vary with sex and age in this long-lived
      dimorphic species. Among the 60% trips that encountered boats at least once, 80%
      of them contained attendance (but attendance followed only 60% of each single
      encounter). Birds were more attracted and remained attending longer when boats
      were hauling lines, despite the measures enforced by this fleet to limit food
      availability during operations. Sex and age of birds had low influence on the
      response to boats, except the year when fewer boats came fishing in the area, and
      younger birds were attending further from boats compared to older birds. Net mass
      gain of birds was similar across sex and not affected by time spent attending
      boats. Our results indicate albatrosses extensively attend this fishery, with no
      clear advantages, questioning impacts on foraging time budgets. Factors
      responsible for sex foraging segregation at larger scale seem not to operate at
      this fleet near the colony and are not consistent with predictions of optimal
      foraging theory on potential individual dominance asymmetries. This approach
      complements studies of large-scale overlap of animals with human subsidies.

PMID- 28515871
TI  - Wolf in sheep's clothing: Model misspecification undermines tests of the neutral
      theory for life histories.
AB  - Understanding the processes behind change in reproductive state along life
      history trajectories is a salient research program in evolutionary ecology. Two
      processes, state dependence and heterogeneity, can drive the dynamics of change
      among states. Both processes can operate simultaneously, begging the difficult
      question of how to tease them apart in practice. The Neutral Theory for Life
      Histories (NTLH) holds that the bulk of variations in life-history trajectories
      is due to state dependence and is hence neutral: Once previous (breeding) state
      is taken into account, variations are mostly random. Lifetime reproductive
      success (LRS), the number of descendants produced over an individual's
      reproductive life span, has been used to infer support for NTLH in natura.
      Support stemmed from accurate prediction of the population-level distribution of
      LRS with parameters estimated from a state dependence model. We show with Monte
      Carlo simulations that the current reliance of NTLH on LRS prediction in a null
      hypothesis framework easily leads to selecting a misspecified model, biased
      estimates and flawed inferences. Support for the NTLH can be spurious because of
      a systematic positive bias in estimated state dependence when heterogeneity is
      present in the data but ignored in the analysis. This bias can lead to spurious
      positive covariance between fitness components when there is in fact an
      underlying trade-off. Furthermore, neutrality implied by NTLH needs a
      clarification because of a probable disjunction between its common understanding
      by evolutionary ecologists and its translation into statistical models of life
      history trajectories. Irrespective of what neutrality entails, testing hypotheses
      about the dynamics of change among states in life histories requires a multimodel
      framework because state dependence and heterogeneity can easily be mistaken for
      each other.

PMID- 28515872
TI  - Increasing copper alters cellular elemental composition (Mo and P) of marine
      diatom.
AB  - The elemental composition (surface adsorbed and internalized fraction of Cu, Mo
      and P) in marine phytoplankton was first examined in cultures of the diatom
      Phaeodactylum tricornutum which were exposed to various levels of Cu
      concentrations ranging from 0.25 to 16 MUmol/L with equivalent free [Cu2+]
      concentrations of 0.4-26 nmol/L. We observed an acceleration of algal growth
      rates (20-40%) with increasing ambient Cu levels, as well as slightly increased
      levels of internalized Cu in cells (2-13 * 10-18 mol/cell) although cellular Cu
      mostly accumulated onto the cell surface (>50% of the total: intracellular +
      surface adsorbed). In particular, we documented for the first time that the
      elemental composition (Mo and P) in algal cells varies dynamically in response to
      increased Cu levels: (1) Cellular P, predominantly in the intracellular
      compartment (>95%), shows with a net consumption as indicated by a gradual
      decrease with increasing [Cu2+] (120->50 * 10-15 mol P/cell) probably due to the
      fact that P, a backbone bioelement, is largely required in forming biological
      compartments such as cell membranes; and (2) cellular Mo, predominantly
      encountered in the intracellular compartment, showed up to tenfold increase in
      concentration in the cultures exposed to Cu, with a peak accumulation of 1.1 * 10
      18 mol Mo/cell occurring in the culture exposed to [Cu2+] at 3.7 nmol/L. Such a
      net cellular Mo accumulation suggests that Mo might be specifically required in
      biological processes, probably playing a counteracting role against Cu.

PMID- 28515873
TI  - Brain morphology of the threespine stickleback (Gasterosteus aculeatus) varies
      inconsistently with respect to habitat complexity: A test of the Clever Foraging
      Hypothesis.
AB  - The Clever Foraging Hypothesis asserts that organisms living in a more spatially
      complex environment will have a greater neurological capacity for cognitive
      processes related to spatial memory, navigation, and foraging. Because the
      telencephalon is often associated with spatial memory and navigation tasks, this
      hypothesis predicts a positive association between telencephalon size and
      environmental complexity. The association between habitat complexity and brain
      size has been supported by comparative studies across multiple species but has
      not been widely studied at the within-species level. We tested for covariation
      between environmental complexity and neuroanatomy of threespine stickleback
      (Gasterosteus aculeatus) collected from 15 pairs of lakes and their parapatric
      streams on Vancouver Island. In most pairs, neuroanatomy differed between the
      adjoining lake and stream populations. However, the magnitude and direction of
      this difference were inconsistent between watersheds and did not covary strongly
      with measures of within-site environmental heterogeneity. Overall, we find weak
      support for the Clever Foraging Hypothesis in our study.

PMID- 28515874
TI  - Universal expressions of population change by the Price equation: Natural
      selection, information, and maximum entropy production.
AB  - The Price equation shows the unity between the fundamental expressions of change
      in biology, in information and entropy descriptions of populations, and in
      aspects of thermodynamics. The Price equation partitions the change in the
      average value of a metric between two populations. A population may be composed
      of organisms or particles or any members of a set to which we can assign
      probabilities. A metric may be biological fitness or physical energy or the
      output of an arbitrarily complicated function that assigns quantitative values to
      members of the population. The first part of the Price equation describes how
      directly applied forces change the probabilities assigned to members of the
      population when holding constant the metrical values of the members-a fixed
      metrical frame of reference. The second part describes how the metrical values
      change, altering the metrical frame of reference. In canonical examples, the
      direct forces balance the changing metrical frame of reference, leaving the
      average or total metrical values unchanged. In biology, relative reproductive
      success (fitness) remains invariant as a simple consequence of the conservation
      of total probability. In physics, systems often conserve total energy.
      Nonconservative metrics can be described by starting with conserved metrics, and
      then studying how coordinate transformations between conserved and nonconserved
      metrics alter the geometry of the dynamics and the aggregate values of
      populations. From this abstract perspective, key results from different subjects
      appear more simply as universal geometric principles for the dynamics of
      populations subject to the constraints of particular conserved quantities.

PMID- 28515875
TI  - Seasonal abundance and habitat use of bird species in and around Wondo Genet
      Forest, south-central Ethiopia.
AB  - The habitat use and seasonal migratory pattern of birds in Ethiopia is less
      explored as compared to diversity studies. To this end, this study aimed at
      investigating the patterns of distribution related to seasonality and the effect
      of habitat characteristics (elevation, slope, and average vegetation height) on
      habitat use of birds of Wondo Genet Forest Patch. A stratified random sampling
      design was used to assess the avian fauna across the four dominant habitat types
      found in the study area: natural forest, wooded grassland, grassland, and
      agroforestry land. A point transect count was employed to investigate avian
      species richness and abundance per habitat type per season. Ancillary data, such
      as elevation above sea level, latitude and longitude, average vegetation height,
      and percent slope inclination, were recorded with a GPS and clinometers per plot.
      A total of 33 migratory bird species were recorded from the area, of which 20
      species were northern (Palearctic) migrants while 13 were inter-African migrants.
      There was a significant difference in the mean abundance of migratory bird
      species between dry and wet seasons (t = 2.13, p = .038, df = 44). The variation
      in mean abundance per plot between the dry and wet seasons in the grassland
      habitat was significant (t = 2.35, p = .051, df = 7). In most habitat types
      during both dry and wet seasons, omnivore birds were the most abundant. While
      slope was a good predictor for bird species abundance in the dry season, altitude
      and average vegetation height accounted more in the wet season. The patch of
      forest and its surrounding is an important bird area for migratory, endemic, and
      global threatened species. Hence, it is conservation priority area, and the study
      suggests that conservation coupled with ecotourism development is needed for its
      sustainability.

PMID- 28515876
TI  - Population genomics reveals a candidate gene involved in bumble bee pigmentation.
AB  - Variation in bumble bee color patterns is well-documented within and between
      species. Identifying the genetic mechanisms underlying such variation may be
      useful in revealing evolutionary forces shaping rapid phenotypic diversification.
      The widespread North American species Bombus bifarius exhibits regional variation
      in abdominal color forms, ranging from red-banded to black-banded phenotypes and
      including geographically and phenotypically intermediate forms. Identifying
      genomic regions linked to this variation has been complicated by strong, near
      species level, genome-wide differentiation between red- and black-banded forms.
      Here, we instead focus on the closely related black-banded and intermediate forms
      that both belong to the subspecies B. bifarius nearcticus. We analyze an RNA
      sequencing (RNAseq) data set and identify a cluster of single nucleotide
      polymorphisms (SNPs) within one gene, Xanthine dehydrogenase/oxidase-like, that
      exhibit highly unusual differentiation compared to the rest of the sequenced
      genome. Homologs of this gene contribute to pigmentation in other insects, and
      results thus represent a strong candidate for investigating the genetic basis of
      pigment variation in B. bifarius and other bumble bee mimicry complexes.

PMID- 28515877
TI  - Sex-specific repeatabilities and effects of relatedness and mating status on
      copulation duration in an acridid grasshopper.
AB  - In species with direct sperm transfer, copulation duration is a crucial trait
      that may affect male and female reproductive success and that may vary with the
      quality of the mating partner. Furthermore, traits such as copulation duration
      represent the outcome of behavioral interactions between the sexes, for which it
      is important-but often difficult-to determine which sex is in phenotypic control.
      Using a double-mating protocol, we compared copulation durations between (1)
      virgin and nonvirgin and (2) sibling and nonsibling mating pairs in rufous
      grasshoppers Gomphocerippus rufus. Nonvirgin copulations took on average
      approximately 30% longer than virgin copulations, whereas relatedness of mating
      partners was not a significant predictor of copulation duration. Longer nonvirgin
      copulations may represent a male adaptation to sperm competition if longer
      copulations allow more sperm to be transferred or function as postinsemination
      mate guarding. The absence of differences between pairs with different degrees of
      relatedness suggests no precopulatory or preinsemination inbreeding avoidance
      mechanism has evolved in this species, perhaps because there is no inbreeding
      depression in this species, or because inbreeding avoidance occurs after
      copulation. Controlling for the effects of male and female mating status (virgin
      vs. nonvirgin) and relatedness (sibling vs. nonsibling), we found significant
      repeatabilities (R) in copulation duration for males (R = 0.33; 95% CI: 0.09
      0.55) but not for females (R = 0.09; 95% CI: 0.00-0.30). Thus, copulation
      durations of males more strongly represent a nontransient trait expressed in a
      consistent manner with different mating partners, suggesting that some aspect of
      the male phenotype may determine copulation duration in this species. However,
      overlapping confidence intervals for our sex-specific repeatability estimates
      indicate that higher sampling effort is required for conclusive evidence.

PMID- 28515878
TI  - A multispecies dependent double-observer model: A new method for estimating
      multispecies abundance.
AB  - Conservation of biological communities requires accurate estimates of abundance
      for multiple species. Recent advances in estimating abundance of multiple
      species, such as Bayesian multispecies N-mixture models, account for multiple
      sources of variation, including detection error. However, false-positive errors
      (misidentification or double counts), which are prevalent in multispecies data
      sets, remain largely unaddressed. The dependent-double observer (DDO) method is
      an emerging method that both accounts for detection error and is suggested to
      reduce the occurrence of false positives because it relies on two observers
      working collaboratively to identify individuals. To date, the DDO method has not
      been combined with advantages of multispecies N-mixture models. Here, we derive
      an extension of a multispecies N-mixture model using the DDO survey method to
      create a multispecies dependent double-observer abundance model (MDAM). The MDAM
      uses a hierarchical framework to account for biological and observational
      processes in a statistically consistent framework while using the accurate
      observation data from the DDO survey method. We demonstrate that the MDAM
      accurately estimates abundance of multiple species with simulated and real
      multispecies data sets. Simulations showed that the model provides both precise
      and accurate abundance estimates, with average credible interval coverage across
      100 repeated simulations of 94.5% for abundance estimates and 92.5% for detection
      estimates. In addition, 92.2% of abundance estimates had a mean absolute percent
      error between 0% and 20%, with a mean of 7.7%. We present the MDAM as an
      important step forward in expanding the applicability of the DDO method to a
      multispecies setting. Previous implementation of the DDO method suggests the MDAM
      can be applied to a broad array of biological communities. We suggest that
      researchers interested in assessing biological communities consider the MDAM as a
      tool for deriving accurate, multispecies abundance estimates.

PMID- 28515879
TI  - Sexual signals reflect telomere dynamics in a wild bird.
AB  - Telomere dynamics in natural populations have been linked to survival,
      reproduction, and energetic investment. Given their putative role in mediating
      life-history trade-offs, telomeres are also a likely candidate for maintaining
      honesty in sexually selected signals; few studies to date, however, have
      demonstrated a correlation between sexual signals and telomere dynamics. Here, we
      show that plumage coloration in male common yellowthroats (Geothlypis trichas) is
      correlated with both relative telomere length and with the rate of telomere loss
      between years. Elevated antioxidant capacity is also associated with reduced
      telomere loss, but only among older males. Previous work in this population has
      demonstrated that males with brighter plumage are in better condition, have
      higher reproductive success, and are more likely to survive over winter. Thus,
      the signal attribute associated with mate choice in this system also conveys
      reliable information about telomere dynamics. At present, it is unclear whether
      telomere maintenance plays a causal role in maintaining signal honesty or whether
      the correlation arises due to underlying variation in individual resources or
      genotypes. We suggest that subsequent work should consider the possibility that
      fundamental trade-offs between signal investment and cell-level processes that
      influence aging and reproductive senescence may provide a foundation for
      understanding the maintenance of sexual signal honesty.

PMID- 28515880
TI  - Resistance and resilience of root fungal communities to water limitation in a
      temperate agroecosystem.
AB  - Understanding crop resilience to environmental stress is critical in predicting
      the consequences of global climate change for agricultural systems worldwide, but
      to date studies addressing crop resiliency have focused primarily on plant
      physiological and molecular responses. Arbuscular mycorrhizal fungi (AMF) form
      mutualisms with many crop species, and these relationships are key in mitigating
      the effects of abiotic stress in many agricultural systems. However, to date
      there is little research examining whether (1) fungal community structure in
      agroecosystems is resistant to changing environmental conditions, specifically
      water limitation and (2) resilience of fungal community structure is moderated by
      agricultural management systems, namely the integration of trees into cropping
      systems. Here, we address these uncertainties through a rainfall reduction field
      experiment that manipulated short-term water availability in a soybean-based
      (Glycine max L. Merr.) agroforest in Southern Ontario, Canada. We employed
      terminal restriction fragment length polymorphism analysis to determine the
      molecular diversity of both general fungal and AMF communities in soybean roots
      under no stress, stress (rainfall shelters added), and poststress (rainfall
      shelters removed). We found that general fungal and AMF communities sampled from
      soybean roots were resistant to rainfall reduction in a monoculture, but not in
      an agroforest. While AMF communities were unchanged after stress removal, general
      fungal communities were significantly different poststress in the agroforest,
      indicating a capacity for resiliency. Our study indicates that generalist fungi
      and AMF are responsive to changes in environmental conditions and that
      agroecosystem management plays a key role in the resistance and resilience of
      fungal communities to water limitation.

PMID- 28515883
TI  - Correlating species and spectral diversities using hyperspectral remote sensing
      in early-successional fields.
AB  - Advances in remote sensing technology can help estimate biodiversity at large
      spatial extents. To assess whether we could use hyperspectral visible near
      infrared (VNIR) spectra to estimate species diversity, we examined the
      correlations between species diversity and spectral diversity in early
      successional abandoned agricultural fields in the Ridge and Valley ecoregion of
      north-central Virginia at the Blandy Experimental Farm. We established plant
      community plots and collected vegetation surveys and ground-level hyperspectral
      data from 350 to 1,025 nm wavelengths. We related spectral diversity (standard
      deviations across spectra) with species diversity (Shannon-Weiner index) and
      evaluated whether these correlations differed among spectral regions throughout
      the visible and near-infrared wavelength regions, and across different spectral
      transformation techniques. We found positive correlations in the visible regions
      using band depth data, positive correlations in the near-infrared region using
      first derivatives of spectra, and weak to no correlations in the red-edge region
      using either of the two spectral transformation techniques. To investigate the
      role of pigment variability in these correlations, we estimated chlorophyll,
      carotenoid, and anthocyanin concentrations of five dominant species in the plots
      using spectral vegetation indices. Although interspecific variability in pigment
      levels exceeded intraspecific variability, chlorophyll was more varied within
      species than carotenoids and anthocyanins, contributing to the lack of
      correlation between species diversity and spectral diversity in the red-edge
      region. Interspecific differences in pigment levels, however, made it possible to
      differentiate these species remotely, contributing to the species-spectral
      diversity correlations. VNIR spectra can be used to estimate species diversity,
      but the relationships depend on the spectral region examined and the spectral
      transformation technique used.

PMID- 28515881
TI  - Effect of Bursaphelenchus xylophilus infection on leaf photosynthetic
      characteristics and resource-use efficiency of Pinus massoniana.
AB  - Pine wilt disease (PWD) is considered as the most destructive forest-invasive
      alien species in China. We measured gas exchange parameters and foliar carbon
      isotope ratios (delta13C) of different infection phases of Masson pine in order
      to investigate the effect of Bursaphelenchus xylophilus infection on
      photosynthetic responses and resource-use efficiency. The results showed that net
      photosynthetic rate (Pn), transpiration rate (T), stomatal conductance (gs), and
      internal CO 2 concentrations (Ci) decreased in the infested trees at
      photosynthetic photon flux density (PPFD) levels from 0 to 2,000 MUmol m-2 s-1
      compared with controls. The maximum net photosynthetic rate (Pmax) was
      significantly declined in the infected trees than in controls (p < .05). There
      also exist significant differences in dark respiration rate (Rd) among different
      infection phases (p < .05), but the value is highest in the middle infection
      phase, followed by the control and then the terminal infection phase. This
      indicates that Pinus massoniana plants need to consume more photosynthetic
      products during the middle infection phase in order to defend against pine sawyer
      beetle feeding and PWD infection. Isotopic analysis revealed a significant
      decrease of the foliar delta13C (p < .05), as much as 2.50/00 lower in the
      infected trees. The mean leaf N content was about 12.94% less in the middle
      infection phase and 27.06% less in the terminal infection phase, causing a
      significant increase of the foliar C:N ratio in infested trees. Both of the net
      photosynthetic rates and foliar delta13C were linearly correlated with the foliar
      N content. We also found a significant decrease (p < .05) of resource-use
      efficiency in PWD-induced P. massoniana plants, which can be attributed to the
      closure of stomatal pores and the inactivation or loss of both Rubisco and other
      key Calvin cycle enzymes. This study highlights the impact of photosynthetic
      characteristics, foliar carbon isotope ratios, and resource-use efficiency of PWD
      induced trees, which can help identify PWD infestations at the photosynthetic and
      physiological levels so as to better facilitate management actions.

PMID- 28515882
TI  - Different categories of biodiversity explain productivity variation after
      fertilization in a Tibetan alpine meadow community.
AB  - The relationship between productivity and biodiversity has long been an important
      issue in ecological research. However, in recent decades, most ecologists have
      primarily focused on species diversity while paying little attention to
      functional diversity and phylogenetic diversity (PD), especially in alpine meadow
      communities following fertilization. In this study, a fertilization experiment
      involving the addition of nitrogen, phosphorus, and a mixture of both was
      implemented in an alpine meadow on the Tibetan Plateau. Species diversity,
      functional diversity, and PD were measured, and the responses of these parameters
      to the variation in productivity were analyzed. We found that the productivity of
      alpine plant communities was colimited by N and P, with N being the principal and
      P being the secondary limiting nutrient. Our results supported the prediction of
      both the mass ratio hypothesis and niche complementarity hypothesis in fertilized
      communities, but these hypotheses were not mutually exclusive. The combination of
      different aspects of biodiversity not only provides a crucial tool to explain the
      variation in productivity and to understand the underlying mechanisms but also
      plays an important role in predicting the variation in productivity of alpine
      meadow communities, which are sensitive to nutrient enrichment in the context of
      global change.

PMID- 28515885
TI  - Evaluating morphometric and metabolic markers of body condition in a small
      cetacean, the harbor porpoise (Phocoena phocoena).
AB  - Mammalian body condition is an important individual fitness metric as it affects
      both survival and reproductive success. The ability to accurately measure
      condition has key implications for predicting individual and population health,
      and therefore monitoring the population-level effects of changing environments.
      No consensus currently exists on the best measure to quantitatively estimate body
      condition in many species, including cetaceans. Here, two measures of body
      condition were investigated in the harbor porpoise (Phocoena phocoena). First,
      the most informative morphometric body condition index was identified. The
      mass/length2 ratio was the most appropriate morphometric index of 10 indices
      tested, explaining 50% of the variation in condition in stranded, male porpoises
      with different causes of death and across age classes (n = 291). Mass/length2 was
      then used to evaluate a second measure, blubber cortisol concentration, as a
      metabolic condition marker. Cortisol is the main glucocorticoid hormone involved
      in the regulation of lipolysis and overall energy balance in mammals, and
      concentrations could provide information on physiological state. Blubber cortisol
      concentrations did not significantly vary around the girth (n = 20), but there
      was significant vertical stratification through the blubber depth with highest
      concentrations in the innermost layer. Concentrations in the dorsal, outermost
      layer were representative of concentrations through the full blubber depth,
      showed variation by sex and age class, and were negatively correlated with
      mass/length2. Using this species as a model for live cetaceans from which
      standard morphometric measurements cannot be taken, but from which blubber biopsy
      samples are routinely collected, cortisol concentrations in the dorsal, outermost
      blubber layer could potentially be used as a biomarker of condition in free
      ranging animals.

PMID- 28515884
TI  - Cooperative breeding shapes post-fledging survival in an Afrotropical forest
      bird.
AB  - For avian group living to be evolutionary stable, multiple fitness benefits are
      expected. Yet, the difficulty of tracking fledglings, and thus estimating their
      survival rates, limits our knowledge on how such benefits may manifest
      postfledging. We radio-tagged breeding females of the Afrotropical cooperatively
      breeding Placid greenbul (Phyllastrephus placidus) during nesting. Tracking these
      females after fledging permitted us to locate juvenile birds, their parents, and
      any helpers present and to build individual fledgling resighting datasets without
      incurring mortality costs or causing premature fledging due to handling or
      transmitter effects. A Bayesian framework was used to infer age-specific
      mortality rates in relation to group size, fledging date, maternal condition, and
      nestling condition. Postfledging survival was positively related to group size,
      with fledglings raised in groups with four helpers showing nearly 30% higher
      survival until independence compared with pair-only offspring, independent of
      fledging date, maternal condition or nestling condition. Our results demonstrate
      the importance of studying the early dependency period just after fledging when
      assessing presumed benefits of cooperative breeding. While studying small, mobile
      organisms after they leave the nest remains highly challenging, we argue that the
      telemetric approach proposed here may be a broadly applicable method to obtain
      unbiased estimates of postfledging survival.

PMID- 28515886
TI  - Aquatic microfauna alter larval food resources and affect development and biomass
      of West Nile and Saint Louis encephalitis vector Culex nigripalpus (Diptera:
      Culicidae).
AB  - Ciliate protists and rotifers are ubiquitous in aquatic habitats and can comprise
      a significant portion of the microbial food resources available to larval
      mosquitoes, often showing substantial declines in abundance in the presence of
      mosquito larvae. This top-down regulation of protists is reported to be strong
      for mosquitoes inhabiting small aquatic containers such as pitcher plants or tree
      holes, but the nature of these interactions with larval mosquitoes developing in
      other aquatic habitats is poorly understood. We examined the effects of these two
      microbial groups on lower trophic level microbial food resources, such as
      bacteria, small flagellates, and organic particles, in the water column, and on
      Culex larval development and adult production. In three independent laboratory
      experiments using two microeukaryote species (one ciliate protist and one
      rotifer) acquired from field larval mosquito habitats and cultured in the
      laboratory, we determined the effects of Culex nigripalpus larval grazing on
      water column microbial dynamics, while simultaneously monitoring larval growth
      and development. The results revealed previously unknown interactions that were
      different from the top-down regulation of microbial groups by mosquito larvae in
      other systems. Both ciliates and rotifers, singly or in combination, altered
      other microbial populations and inhibited mosquito growth. It is likely that
      these microeukaryotes, instead of serving as food resources, competed with early
      instar mosquito larvae for microbes such as small flagellates and bacteria in a
      density-dependent manner. These findings help our understanding of the basic
      larval biology of Culex mosquitoes, variation in mosquito production among
      various larval habitats, and may have implications for existing vector control
      strategies and for developing novel microbial-based control methods.

PMID- 28515888
TI  - Unpacking brown food-webs: Animal trophic identity reflects rampant microbivory.
AB  - Detritivory is the dominant trophic paradigm in most terrestrial, aquatic, and
      marine ecosystems, yet accurate measurement of consumer trophic position within
      detrital (="brown") food webs has remained unresolved. Measurement of detritivore
      trophic position is complicated by the fact that detritus is suffused with
      microbes, creating a detrital complex of living and nonliving biomass. Given that
      microbes and metazoans are trophic analogues of each other, animals feeding on
      detrital complexes are ingesting other detritivores (microbes), which should
      elevate metazoan trophic position and should be rampant within brown food webs.
      We tested these hypotheses using isotopic (15N) analyses of amino acids extracted
      from wild and laboratory-cultured consumers. Vertebrate (fish) and invertebrate
      detritivores (beetles and moths) were reared on detritus, with and without
      microbial colonization. In the field, detritivorous animal specimens were
      collected and analyzed to compare trophic identities among laboratory-reared and
      free-roaming detritivores. When colonized by bacteria or fungi, the trophic
      positions of detrital complexes increased significantly over time. The magnitude
      of trophic inflation was mediated by the extent of microbial consumption of
      detrital substrates. When detrital complexes were fed to vertebrate and
      invertebrate animals, the consumers registered similar degrees of trophic
      inflation, albeit one trophic level higher than their diets. The wild-collected
      detritivore fauna in our study exhibited significantly elevated trophic
      positions. Our findings suggest that the trophic positions of detrital complexes
      rise predictably as microbes convert nonliving organic matter into living
      microbial biomass. Animals consuming such detrital complexes exhibit similar
      trophic inflation, directly attributable to the assimilation of microbe-derived
      amino acids. Our data demonstrate that detritivorous microbes elevate metazoan
      trophic position, suggesting that detritivory among animals is, functionally,
      omnivory. By quantifying the impacts of microbivory on the trophic positions of
      detritivorous animals and then tracking how these effects propagate "up" food
      chains, we reveal the degree to which microbes influence consumer groups within
      trophic hierarchies. The trophic inflation observed among our field-collected
      fauna further suggests that microbial proteins represent an immense contribution
      to metazoan biomass. Collectively, these findings provide an empirical basis to
      interpret detritivore trophic identity, and further illuminate the magnitude of
      microbial contributions to food webs.

PMID- 28515887
TI  - Bottom-up and top-down effects of tree species diversity on leaf insect
      herbivory.
AB  - The diversity of plant neighbors commonly results in direct, bottom-up effects on
      herbivore ability to locate their host, and in indirect effects on herbivores
      involving changes in plant traits and a top-down control by their enemies. Yet,
      the relative contribution of bottom-up and top-down forces remains poorly
      understood. We also lack knowledge on the effect of abiotic constraints such as
      summer drought on the strength and direction of these effects. We measured leaf
      damage on pedunculate oak (Quercus robur), alone or associated with birch, pine
      or both in a long-term tree diversity experiment (ORPHEE), where half of the
      plots were irrigated while the other half remained without irrigation and
      received only rainfall. We tested three mechanisms likely to explain the effects
      of oak neighbors on herbivory: (1) Direct bottom-up effects of heterospecific
      neighbors on oak accessibility to herbivores, (2) indirect bottom-up effects of
      neighbors on the expression of leaf traits, and (3) top-down control of
      herbivores by predators. Insect herbivory increased during the growth season but
      was independent of neighbor identity and irrigation. Specific leaf area, leaf
      toughness, and thickness varied with neighbor identity while leaf dry matter
      content or C:N ratio did not. When summarized in a principal component analysis
      (PCA), neighbor identity explained 87% of variability in leaf traits. PCA axes
      partially predicted herbivory. Despite greater rates of attack on dummy
      caterpillars in irrigated plots, avian predation, and insect herbivory remained
      unrelated. Our study suggests that neighbor identity can indirectly influence
      insect herbivory in mixed forests by modifying leaf traits. However, we found
      only partial evidence for these trait-mediated effects and suggest that more
      attention should be paid to some unmeasured plant traits such as secondary
      metabolites, including volatile organic compounds, to better anticipate the
      effects of climate change on plant-insect interactions in the future.

PMID- 28515889
TI  - Phenotypic plasticity in female mate choice behavior is mediated by an
      interaction of direct and indirect genetic effects in Drosophila melanogaster.
AB  - Female mate choice is a complex decision-making process that involves many
      context-dependent factors. In Drosophila melanogaster, a model species for the
      study of sexual selection, indirect genetic effects (IGEs) of general social
      interactions can influence female mate choice behaviors, but the potential
      impacts of IGEs associated with mating experiences are poorly understood. Here,
      we examined whether the IGEs associated with a previous mating experience had an
      effect on subsequent female mate choice behaviors and quantified the degree of
      additive genetic variation associated with this effect. Females from 21 different
      genetic backgrounds were housed with males from one of two distinct genetic
      backgrounds for either a short (3 hr) or long (48 hr) exposure period and their
      subsequent mate choice behaviors were scored. We found that the genetic identity
      of a previous mate significantly influenced a female's subsequent interest in
      males and preference of males. Additionally, a hemiclonal analysis revealed
      significant additive genetic variation associated with experience-dependent mate
      choice behaviors, indicating a genotype-by-environment interaction for both of
      these parameters. We discuss the significance of these results with regard to the
      evolution of plasticity in female mate choice behaviors and the maintenance of
      variation in harmful male traits.

PMID- 28515890
TI  - Sex-dependent infection causes nonadditive effects on kissing bug fecundity.
AB  - The influence of parasites on host reproduction has been widely studied in
      natural and experimental conditions. Most studies, however, have evaluated the
      parasite impact on female hosts only, neglecting the contribution of males for
      host reproduction. This omission is unfortunate as sex-dependent infection may
      have important implications for host-parasite associations. Here, we evaluate for
      the first time the independent and nonindependent effects of gender infection on
      host reproductive success using the kissing bug Mepraia spinolai and the
      protozoan Trypanosoma cruzi as model system. We set up four crossing treatments
      including the following: (1) both genders infected, (2) both genders uninfected,
      (3) males infected-females uninfected, and (4) males uninfected-females infected,
      using fecundity measures as response variables. Interactive effects of infection
      between sexes were prevalent. Uninfected females produced more and heavier eggs
      when crossed with uninfected than infected males. Uninfected males, in turn,
      sired more eggs and nymphs when crossed with uninfected than infected females.
      Unexpectedly, infected males sired more nymphs when crossed with infected than
      uninfected females. These results can be explained by the effect of parasitism on
      host body size. As infection reduced size in both genders, infection on one sex
      only creates body size mismatches and mating constraints that are not present in
      pairs with the same infection status. Our results indicate the fitness impact of
      parasitism was contingent on the infection status of genders and mediated by body
      size. As the fecundity impact of parasitism cannot be estimated independently for
      each gender, inferences based only on female host infection run the risk of
      providing biased estimates of parasite-mediated impact on host reproduction.

PMID- 28515892
TI  - Timing and body condition of dichromatic Black Redstarts during autumn migration.
AB  - Individual variation in postjuvenile molt in male Black Redstart is pronounced
      with about 90% of young males retaining female-like coloration (cairei plumage
      type) and about 10% acquiring adult male-like feathers (paradoxus plumage type).
      We examined whether autumn migration timing and body condition differed between
      individuals of the two plumage types. We used the data of 10,977 Black Redstarts
      captured during autumn at a ringing site in northern Switzerland where a protocol
      to record plumage types of captures has been applied since 1980. As cairei
      individuals cannot be distinguished from young females while sexing is
      comparatively easy for paradoxus individuals, the proportion of missing data on
      sex was likely to be higher for cairei individuals than for paradoxus
      individuals. We formally accounted for captures with unidentified sex using a
      Bayesian approach and conducted a simulation study to show that our approach was
      able to provide unbiased results even if the proportion of unsexed captures was
      high. Applying the method to the Black Redstart data, we found that the
      proportion of individuals with paradoxus plumage type increased from 7.6% in 1980
      to 18.1% in 2013. Individuals with the paradoxus plumage type were on average
      0.25 g heavier and had 0.62 mm longer third primaries than individuals with the
      cairei plumage type. However, we found no support for our expectation of later
      migration of paradoxus males compared to cairei individuals based on the
      assumption that paradoxus individuals should occupy autumn territories like adult
      males. Our results shed new light on the understudied timing of autumn migration
      in birds and are in line with available studies on Black Redstarts, suggesting a
      molt-constraint that allows only young males in good body condition to molt into
      adult-like plumages.

PMID- 28515894
TI  - Reproductive ecology of interior least tern and piping plover in relation to
      Platte River hydrology and sandbar dynamics.
AB  - Investigations of breeding ecology of interior least tern (Sternula antillarum
      athalassos) and piping plover (Charadrius melodus) in the Platte River basin in
      Nebraska, USA, have embraced the idea that these species are physiologically
      adapted to begin nesting concurrent with the cessation of spring floods. Low use
      and productivity on contemporary Platte River sandbars have been attributed to
      anthropomorphically driven changes in basin hydrology and channel morphology or
      to unusually late annual runoff events. We examined distributions of least tern
      and piping plover nest initiation dates in relation to the hydrology of the
      historical central Platte River (CPR) and contemporary CPR and lower Platte River
      (LPR). We also developed an emergent sandbar habitat model to evaluate the
      potential for reproductive success given observed hydrology, stage-discharge
      relationships, and sandbar height distributions. We found the timing of the late
      spring rise to be spatially and temporally consistent, typically occurring in mid
      June. However, piping plover nest initiation peaks in May and least tern nest
      initiation peaks in early June; both of which occur before the late spring rise.
      In neither case does there appear to be an adaptation to begin nesting concurrent
      with the cessation of spring floods. As a consequence, there are many years when
      no successful reproduction is possible because emergent sandbar habitat is
      inundated after most nests have been initiated, and there is little potential for
      successful renesting. The frequency of nest inundation, in turn, severely limits
      the potential for maintenance of stable species subpopulations on Platte River
      sandbars. Why then did these species expand into and persist in a basin where the
      hydrology is not ideally suited to their reproductive ecology? We hypothesize the
      availability and use of alternative off-channel nesting habitats, like sandpits,
      may allow for the maintenance of stable species subpopulations in the Platte
      River basin.

PMID- 28515893
TI  - Evolutionary stability and the rarity of grandmothering.
AB  - The provision of intergenerational care, via the Grandmother Hypothesis, has been
      implicated in the evolution of postfertile longevity, particularly in humans.
      However, if grandmothering does provide fitness benefits, a key question is why
      has it evolved so infrequently? We investigate this question with a combination
      of life-history and evolutionary game theory. We derive simple eligibility and
      stability thresholds, both of which must be satisfied if intergenerational care
      is first to evolve and then to persist in a population. As one threshold becomes
      easier to fulfill, the other becomes more difficult, revealing a conflict between
      the two. As such, we suggest that, in fact, we should expect the evolution of
      grandmothering to be rare.

PMID- 28515891
TI  - Longevity is associated with relative brain size in birds.
AB  - Brain size of vertebrates has long been recognized to evolve in close association
      with basic life-history traits, including lifespan. According to the cognitive
      buffer hypothesis, large brains facilitate the construction of behavioral
      responses against novel socioecological challenges through general cognitive
      processes, which should reduce mortality and increase lifespan. While the
      occurrence of brain size-lifespan correlation has been well documented in
      mammals, much less evidence exists for a robust link between brain size and
      longevity in birds. The aim of this study was to use phylogenetically controlled
      comparative approach to test for the relationship between brain size and
      longevity among 384 avian species from 23 orders. We used maximum lifespan and
      maximum reproductive lifespan as the measures of longevity and accounted for a
      set of possible confounding effects, such as allometry, sampling effort,
      geographic patterns, and life-history components (clutch size, incubation length,
      and mode of development). We found that both measures of longevity positively
      correlated with relative (residual) brain size. We also showed that major
      diversification of brain size preceded diversification of longevity in avian
      evolution. In contrast to previous findings, the effect of brain size on
      longevity was consistent across lineages with different development patterns,
      although the relatively low strength of this correlation could likely be
      attributed to the ubiquity of allomaternal care associated with the altricial
      mode of development. Our study indicates that the positive relationship between
      brain size and longevity in birds may be more general than previously thought.

PMID- 28515895
TI  - Disruptive natural selection predicts divergence between the sexes during
      adaptive radiation.
AB  - Evolution of sexual dimorphism in ecologically relevant traits, for example, via
      resource competition between the sexes, is traditionally envisioned to stall the
      progress of adaptive radiation. An alternative view is that evolution of
      ecological sexual dimorphism could in fact play an important positive role by
      facilitating sex-specific adaptation. How competition-driven disruptive
      selection, ecological sexual dimorphism, and speciation interact during real
      adaptive radiations is thus a critical and open empirical question. Here, we
      examine the relationships between these three processes in a clade of salamanders
      that has recently radiated into divergent niches associated with an aquatic life
      cycle. We find that morphological divergence between the sexes has occurred in a
      combination of head shape traits that are under disruptive natural selection
      within breeding ponds, while divergence among species means has occurred
      independently of this disruptive selection. Further, we find that adaptation to
      aquatic life is associated with increased sexual dimorphism across taxa,
      consistent with the hypothesis of clade-wide character displacement between the
      sexes. Our results suggest the evolution of ecological sexual dimorphism may play
      a key role in niche divergence among nascent species and demonstrate that
      ecological sexual dimorphism and ecological speciation can and do evolve
      concurrently in the early stages of adaptive radiation.

PMID- 28515896
TI  - A worldwide phylogeography of the whiteworm lichens Thamnolia reveals three
      lineages with distinct habitats and evolutionary histories.
AB  - Thamnolia is a lichenized fungus with an extremely wide distribution, being
      encountered in arctic and alpine environments in most continents. In this study,
      we used molecular markers to investigate the population structure of the fungal
      symbiont and the associated photosynthetic partner of Thamnolia. By analyzing
      molecular, morphological, and chemical variation among 253 specimens covering the
      species distribution range, we revealed the existence of three mycobiont
      lineages. One lineage (Lineage A) is confined to the tundra region of Siberia and
      the Aleutian Islands, a second (Lineage B) is found in the high alpine region of
      the Alps and the Carpathians Mountains, and a third (Lineage C) has a worldwide
      distribution and covers both the aforementioned ecosystems. Molecular dating
      analysis indicated that the split of the three lineages is older than the last
      glacial maximum, but the distribution ranges and the population genetic analyses
      suggest an influence of last glacial period on the present-day population
      structure of each lineage. We found a very low diversity of Lineage B, but a
      higher and similar one in Lineages A and C. Demographic analyses suggested that
      Lineage C has its origin in the Northern Hemisphere, possibly Scandinavia, and
      that it has passed through a bottleneck followed by a recent population
      expansion. While all three lineages reproduce clonally, recombination tests
      suggest rare or past recombination in both Lineages A and C. Moreover, our data
      showed that Lineage C has a comparatively low photobiont specificity, being found
      associated with four widespread Trebouxia lineages (three of them also shared
      with other lichens), while Lineages A and B exclusively harbor T. simplex s. lat.
      Finally, we did not find support for the recognition of taxa in Thamnolia based
      on either morphological or chemical characters.

PMID- 28515897
TI  - Exploitation promotes earlier sex change in a protandrous patellid limpet,
      Patella aspera Roding, 1798.
AB  - Exploitation of organisms can prompt the reduction in the number and size of
      target populations consequently affecting reproductive output and replenishment.
      Here, we investigated the effects of exploitation on the population structure of
      a protandrous patellid limpet, Patella aspera, an overexploited Macaronesian
      endemic. Timed dives were used to collect animals across eleven islands of
      Macaronesia. Individuals were inspected for sex, size, and gonad stage. Using
      catch effort (time per person) per island coastal perimeter as a surrogate for
      exploitation intensity, we found that limpet abundance (CPUE) and mean size
      tended to decrease with exploitation intensity. When considering the sex of
      animals separately, the size of the largest male, but not females, decreased with
      exploitation. In contrast, the size of the smallest male remained relatively
      consistent, whereas the size of the smallest female decreased significantly with
      exploitation. As exploitation is mostly targeting larger individuals, results
      suggest that males are compensating the removal of larger females, by undergoing
      sex change at smaller and presumably earlier sizes. These results have wider
      implications for the conservation of P. aspera, as a reduction in female size
      will likely affect the numbers of oocytes produced, hence fecundity. Regulations
      promoting the protection of the larger-sized animals should be enforced to
      safeguard the replenishment of the population.

PMID- 28515898
TI  - Fungal-host diversity among mycoheterotrophic plants increases proportionally to
      their fungal-host overlap.
AB  - The vast majority of plants obtain an important proportion of vital resources
      from soil through mycorrhizal fungi. Generally, this happens in exchange of
      photosynthetically fixed carbon, but occasionally the interaction is
      mycoheterotrophic, and plants obtain carbon from mycorrhizal fungi. This process
      results in an antagonistic interaction between mycoheterotrophic plants and their
      fungal hosts. Importantly, the fungal-host diversity available for plants is
      restricted as mycoheterotrophic interactions often involve narrow lineages of
      fungal hosts. Unfortunately, little is known whether fungal-host diversity may be
      additionally modulated by plant-plant interactions through shared hosts. Yet,
      this may have important implications for plant competition and coexistence. Here,
      we use DNA sequencing data to investigate the interaction patterns between
      mycoheterotrophic plants and arbuscular mycorrhizal fungi. We find no
      phylogenetic signal on the number of fungal hosts nor on the fungal hosts shared
      among mycoheterotrophic plants. However, we observe a potential trend toward
      increased phylogenetic diversity of fungal hosts among mycoheterotrophic plants
      with increasing overlap in their fungal hosts. While these patterns remain for
      groups of plants regardless of location, we do find higher levels of overlap and
      diversity among plants from the same location. These findings suggest that
      species coexistence cannot be fully understood without attention to the two sides
      of ecological interactions.

PMID- 28515899
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1002/ece3.1910.].

PMID- 28503295
TI  - Building the infrastructure to make science metrics more scientific.
AB  - Research leaders, policy makers and science strategists need evidence to support
      decision-making around research funding investment, policy and strategy.  In
      recent years there has been a rapid expansion in the data sources available that
      shed light onto aspects of research quality, excellence, use, re-use and
      attention, and engagement. This is at a time when the modes and routes to share
      and communicate research findings and data are also changing.  In this opinion
      piece, we outline a series of considerations and interventions that are needed to
      ensure that research metric development is accompanied by appropriate scrutiny
      and governance, to properly support the needs of research assessors and decision
      makers, while securing the confidence of the research community. Key among these
      are: agreed 'gold standards' around datasets and methodologies; full transparency
      around the calculation and derivation of research-related indicators; and a
      strategy and roadmap to take the discipline of scientific indicators and research
      assessment to a more robust and sustainable place.

PMID- 28515902
TI  - Sites of colonization in hospitalized patients with infections caused by extended
      spectrum beta-lactamase organisms: a prospective cohort study.
AB  - BACKGROUND: The objective of this study was to determine whether patients
      infected with extended-spectrum beta-lactamase (ESBL)-producing organisms are
      colonized at multiple body sites. METHODS: This was a prospective cohort study at
      a tertiary care center in Beirut, Lebanon. Hospitalized patients with infections
      caused by ESBL-producing organisms were included. Cultures were obtained from the
      primary site of infection as well as from other sites (skin, nasopharynx, urine,
      rectum). Molecular analysis was performed on isolates to determine clonal
      relatedness. RESULTS: One hundred patients were included in the study. Only 22
      patients had positive cultures from sites other than the primary site of
      infection. The most common ESBL gene was CTX-M-15 followed by TEM-1. In 11 of 22
      patients, isolates collected from the same patient were 100% genetically related,
      while in the remaining patients, genomic relatedness ranged from 42.9% to 97.1%.
      CONCLUSIONS: Colonization at sites other than the primary site of infection was
      not common among our patient population infected with ESBL-producing organisms.
      The dynamics of transmission of these bacterial strains should be studied in
      further prospective studies to determine the value of routine active surveillance
      and the need for expanded precautions in infected and colonized patients.

PMID- 28515901
TI  - Experimental identification and computational characterization of a novel
      extracellular metalloproteinase produced by Clostridium sordellii.
AB  - Clostridium sordellii is a lethal pathogen for both animals and humans. Severe
      capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR),
      are hallmark features of C. sordellii infections and contribute to its high
      mortality rate. Here we report the discovery of a previously unknown and
      uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves
      human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule
      critical to hematopoietic precursor retention and leukocyte diapedesis. We
      successfully identified the open reading frame encoding Mcs1 within the ATCC 9714
      genome and developed an Deltamcs1 mutant strain using the ClosTron mutagenesis
      technology. No VCAM-1 proteolysis was observed from exotoxins collected from
      mutant strain cultures. Using advanced protein structural modeling and molecular
      dynamics simulation techniques, the 3D molecular structure and conformational
      features of Mcs1 were also characterized. Our data demonstrates that Mcs1
      proteolytic activity is controlled by the electrostatic interactions between
      Glu113 and Arg227 residues and the gating motions within its cleft region. This
      pilot interdisciplinary investigation provided crucial experimental evidence of
      the existence of Mcs1 in C. sordellii and molecular insights into its 3D
      structure and proteolytic activity. These findings have the potential to help
      advance new therapeutics and diagnostics against deadly C. sordellii infections.
      Follow-up in vitro and in vivo work is under way to further characterize Mcs1
      enzymatic kinetics and its role in C. sordellii pathogenesis.

PMID- 28515904
TI  - Weekly screening supports terminating nosocomial transmissions of vancomycin
      resistant enterococci on an oncologic ward - a retrospective analysis.
AB  - BACKGROUND: To investigate the impact of weekly screening within the bundle of
      infection control measures to terminate vancomycin-resistant enterococci (VRE)
      transmissions on an oncologic ward. METHODS: A cluster of 12 VRE colonisation and
      five infections was detected on an oncologic ward between January and April 2015.
      Subsequently, the VRE point prevalence was detected and, as part of a the bundle
      of infection control strategies to terminate the VRE cluster, we isolated
      affected patients, performed hand hygiene training among staff on ward, increased
      observations by infection control specialists, intensified surface disinfection,
      used personal protective equipment and initiated an admission screening in May
      2015. After a further nosocomial VRE infection in August 2015, a weekly screening
      strategy of all oncology patients on the respective ward was established while
      admission screening was continued. Whole genome sequencing (WGS)-based typing was
      applied to determine the clonal relationship of isolated strains. RESULTS:
      Initially, 12 of 29 patients were VRE colonised; of these 10 were hospital
      acquired. During May to August, on average 7 of 40 patients were detected to be
      VRE colonised per week during the admission screening, showing no significant
      decline compared to the initial situation. WGS-based typing revealed five
      different clusters of which three were due to vanB- and two vanA-positive
      enterococci. After an additional weekly screening was established, the number of
      colonised patients significantly declined to 1/53 and no further nosocomial cases
      were detected. CONCLUSIONS: Weekly screening helped to differentiate between
      nosocomial and community-acquired VRE cases resulting in earlier infection
      control strategies on epidemic situations for a successful termination of
      nosocomial VRE transmissions.

PMID- 28515903
TI  - The threat of antimicrobial resistance in developing countries: causes and
      control strategies.
AB  - The causes of antimicrobial resistance (AMR) in developing countries are complex
      and may be rooted in practices of health care professionals and patients'
      behavior towards the use of antimicrobials as well as supply chains of
      antimicrobials in the population. Some of these factors may include inappropriate
      prescription practices, inadequate patient education, limited diagnostic
      facilities, unauthorized sale of antimicrobials, lack of appropriate functioning
      drug regulatory mechanisms, and non-human use of antimicrobials such as in animal
      production. Considering that these factors in developing countries may vary from
      those in developed countries, intervention efforts in developing countries need
      to address the context and focus on the root causes specific to this part of the
      world. Here, we describe these health-seeking behaviors that lead to the threat
      of AMR and healthcare practices that drive the development of AMR in developing
      countries and we discuss alternatives for disease prevention as well as other
      treatment options worth exploring.

PMID- 28515906
TI  - Measurement accuracy of total cell volume by automated dialyzer reprocessing: A
      prospective cohort study.
AB  - INTRODUCTION: Dialyzer reprocessing machines have replaced human labor in
      preparing re-usable dialyzers. It also made the process of total cell volume
      (TCV) measurement become faster. Nevertheless, there has been a lack of data on
      efficacy of weight evaluation on TCV by machine compared to volume evaluation by
      the conventional method. The aim of this study was to evaluate the efficacy of
      TCV measurement performed by Kidney-Kleen(r) reprocessing machine, produced by
      MEDITOP Company in Thailand, compared to that of the conventional method.
      METHODS: This prospective cohort study was performed during September 2014 to
      December 2015.The low-flux (N = 101) and high-flux dialyzers (N = 100) were
      included for TCV evaluation. Reused times were up to 5 in the low-flux and 20 in
      the high-flux dialyzers. The Bland Altman analysis was used to evaluate value
      measured by different methods. RESULTS: The values measured by weight evaluation
      (by machine) were higher than those obtained by volumetric evaluation of the
      conventional method in the low-flux (0.81 +/- 0.20%) and high-flux (1.32 +/-
      0.39%) dialyzers. The correlation of TCV values of the two methods were r = 0.98,
      p < 0.001 and r = 0.71, p < 0.001 for the low- and high-flux dialyzers. Moreover,
      there was robust association and agreement between the two methods, confirmed by
      the Bland-Altman Analysis, which suggested that the values acquired by machine
      were within the limits of agreement, indicating acceptable accuracy of equipment.
      CONCLUSION: The approach of measurement differed from that of the conventional
      method (weight evaluation was used instead of volumetric evaluation), the
      reprocessing machine could offer accurate results.

PMID- 28515905
TI  - Colonization of long term care facility patients with MDR-Gram-negatives during
      an Acinetobacter baumannii outbreak.
AB  - BACKGROUND: We aimed to determine the prevalence of colonization by multidrug
      resistant Gram-negative bacteria including ESBL-producing enterobacteriaceae,
      carbapenem-resistant enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter
      baumannii at two wards caring long term for patients with disorder of
      consciousness at the Geriatric Health Centers Graz, Austria. During our study we
      detected two A. baumannii outbreaks. METHODS: In August 2015, we conducted a
      point-prevalence study. Inguinal and perianal swabs were taken from 38 patients
      and screened for multidrug-resistant Gram-negative rods using standard
      procedures. Six months after the initial investigation all patients were sampled
      again and use of antibiotics during the past 6 months and mortality was
      registered. Genetic relatedness of bacteria was evaluated by DiversiLab system.
      RESULTS: Fifty percent of patients were colonized by multidrug-resistant Gram
      negative isolates. Five patients harboured ESBL-producing enterobacteriaceae. No
      carbapenem-resistant enterobacteriaceae were detected. 13/38 patients were
      colonized by A. baumannii isolates (resistant to ciprofloxacin but susceptible to
      carbapenems). There was a significant difference in the prevalence of
      colonization by A. baumannii between ward 2 and ward 1 (60% vs. 5.6%, p < 0.001).
      Two clusters of A. baumannii isolates were identified including one isolate
      detected on a chair in a patient's room. CONCLUSIONS: We detected a high
      prevalence of two multidrug-resistant A. baumannii strains in patients with
      disorder of consciousness at a LTCF in Graz, Austria. Our findings strongly
      suggest nosocomial cross-transmission between patients. An active surveillance
      strategy is warranted to avoid missing newly emerging pathogens.

PMID- 28515663
TI  - Measurement of jet activity produced in top-quark events with an electron, a muon
      and two b-tagged jets in the final state in pp collisions at [Formula: see text]
      TeV with the ATLAS detector.
AB  - Measurements of jet activity in top-quark pair events produced in proton-proton
      collisions are presented, using 3.2 fb[Formula: see text] of pp collision data at
      a centre-of-mass energy of 13 TeV collected by the ATLAS experiment at the Large
      Hadron Collider. Events are chosen by requiring an opposite-charge [Formula: see
      text] pair and two b-tagged jets in the final state. The normalised differential
      cross-sections of top-quark pair production are presented as functions of
      additional-jet multiplicity and transverse momentum, [Formula: see text]. The
      fraction of signal events that do not contain additional jet activity in a given
      rapidity region, the gap fraction, is measured as a function of the [Formula: see
      text] threshold for additional jets, and is also presented for different
      invariant mass regions of the [Formula: see text] system. All measurements are
      corrected for detector effects and presented as particle-level distributions
      compared to predictions with different theoretical approaches for QCD radiation.
      While the kinematics of the jets from top-quark decays are described well, the
      generators show differing levels of agreement with the measurements of
      observables that depend on the production of additional jets.

PMID- 28515907
TI  - Factors influencing risky single occasion drinking in Canada and policy
      implications.
AB  - BACKGROUND: Misuse of alcohol, including single risky occasion drinking (RSOD) is
      associated with a number of health, social and economic consequences. While
      research demonstrates that many factors contribute to individuals' drinking
      practices, little is known about risk factors that contribute to RSOD in the
      Canadian population. The objectives of this study are to examine the patterns of
      RSOD in Canada, to identify factors associated with RSOD, and to explore policy
      implications. METHODS: The Canadian Community Health Survey (CCHS) 2009-2010
      annual component was used to conduct all the analyses in this paper. We used two
      models: (1) a binary logistic regression model, and (2) a multinomial logistic
      regression model, to identify factors that were significantly associated with our
      dependent variables, RSOD engagement and frequency of RSOD, respectively.
      RESULTS: Daily smokers were 6.20 times more likely to engage in frequent RSOD
      than those who never smoke. Males were 4.69 times more likely to engage in risky
      RSOD. We also found significant associations between the frequency of RSOD and
      Province/Territory of residence, income and education, marital status and
      perceived health status. Finally, stress was associated with engaging in
      infrequent RSOD. CONCLUSIONS: Our finding associating daily smoking with risk
      alcohol intake specifically suggests the possibility of combining public health
      interventions for both. The study findings also indicate that education is a
      protective factor, further supporting the role of education as a major
      determinant of health. The significant provincial variation we found also point
      to the need to study this issue further and understand the links between
      provincial level policies and RSOD.

PMID- 28515908
TI  - Renal manifestations of primary mitochondrial disorders.
AB  - The aim of the present review was to summarize and discuss previous findings
      concerning renal manifestations of primary mitochondrial disorders (MIDs). A
      literature review was performed using frequently used databases. The study
      identified that primary MIDs frequently present as mitochondrial multiorgan
      disorder syndrome (MIMODS) at onset or in the later course of the MID.
      Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs
      include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts,
      renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental
      glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or
      malign neoplasms. Among the syndromic MIDs, renal involvement has been most
      frequently reported in patients with mitochondrial encephalomyopathy, lactic
      acidosis, and stroke-like episodes syndrome, Kearns-Sayre syndrome, Leigh
      syndrome and mitochondrial depletion syndromes. Only in single cases was renal
      involvement also reported in chronic progressive external ophthalmoplegia,
      Pearson syndrome, Leber's hereditary optic neuropathy, coenzyme-Q deficiency, X
      linked sideroblastic anemia and ataxia, myopathy, lactic acidosis, and
      sideroblastic anemia, pyruvate dehydrogenase deficiency, growth retardation,
      aminoaciduria, cholestasis, iron overload, lactacidosis, and early death, and
      hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis
      syndrome. The present study proposes that the frequency of renal involvement in
      MIDs is probably underestimated. Diagnosis of renal involvement follows general
      guidelines and treatment is symptomatic. Thus, renal manifestations of primary
      MIDs require recognition and appropriate management, as they determine the
      outcome of MID patients.

PMID- 28515909
TI  - Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous
      system tissues.
AB  - The hepatokine fibroblast growth factor 21 (FGF21) is a novel polypeptide ligand,
      which is involved in glucose and lipid metabolism, and contributes significantly
      to lowering body weight and enhancing insulin sensitivity. A large number of pre
      clinical and clinical results demonstrate that FGF21 is a potential drug target
      for treating obesity and type 2 diabetes mellitus. In the present review, the
      tissue specific actions and molecular mechanisms of FGF21 are discussed with a
      focus on the liver, adipose tissue and nervous system, as well as investigating
      the outcomes of clinical trials of FGF21, with the aim of interpreting and
      delineating the complexity physiology of FGF21.

PMID- 28515910
TI  - Biocompatibility of biological material polylactic acid with stem cells from
      human exfoliated deciduous teeth.
AB  - To investigate the biocompatibility of the biomaterial, polylactic acid (PLA)
      with stem cells from human exfoliated deciduous teeth (SHED) and its induction of
      mineralization as a type of scaffold material. To determine the impacts of
      biomaterial PLA on proliferation and mineralization of SHED, the expression of
      surface molecules of SHED isolated and cultured in vitro was detected by flow
      cytometry. In addition, cell proliferation was measured using MTT and Edu assays,
      and the evaluation of mineralized differentiation was performed using Alizarin
      Red S staining. In addition, the expression levels of osteogenic marker genes
      were measured by reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) and western blot analysis. SHED were successfully isolated and identified.
      The MTT and Edu results indicated that the proliferation of SHED cultured in PLA
      and normal medium was not significantly different. The Alizarin Red S staining
      demonstrated that the mineralization capability was significantly higher in the
      SHED that were cultured in PLA medium. Furthermore, RT-qPCR and western blot
      analyses indicated that the expression levels of osteogenic marker genes were
      higher in the SHED cultured in PLA medium. These results suggested that PLA
      possesses good biocompatibility with SHED and may effectively induce the
      mineralization of SHED and serve as a scaffold material.

PMID- 28515912
TI  - Accelerated carcinogenesis following liver resection in chronically inflamed
      livers: A window of opportunity for treatment.
AB  - The long-term prognosis following resection of hepatocellular carcinoma (HCC)
      remains unsatisfactory as a result of a high incidence of recurrence. Prevention
      of recurrence is the most important strategy to improve the long-term survival
      results. The role of hepatectomy itself, as an accelerator of carcinogenesis, has
      not been adequately evaluated in HCC patients. Studies in animal models have
      revealed a link between liver regeneration under chronic inflammation and hepatic
      tumorigenesis. Inhibiting different signal transduction pathways during liver
      regeneration without compromising the ability of the liver to regenerate appears
      to be a rational strategy and may decrease HCC development and recurrence. If
      this hypothesis is proven using animal models, this strategy could be evaluated
      in future clinical trials in humans.

PMID- 28515916
TI  - ECOG is as independent predictor of the response to chemotherapy, overall
      survival and progression-free survival in carcinoma of unknown primary site.
AB  - The aim of the present study was to determine whether age, gender, functional
      status, histology, tumor location, number of metastases, and levels of the tumor
      markers, lactate dehydrogenase (LDH) and albumin, are poor prognostic factors for
      the response to chemotherapy in patients with carcinoma of unknown primary site.
      A total of 149 patients diagnosed with carcinoma of unknown primary site that was
      histologically confirmed, and treated with chemotherapy in the Oncology Hospital,
      National Medical Center, 'Century XXI' IMSS, Mexico City, Mexico during the
      period between January 2002 to December 2009, were carefully selected for the
      present study. The analysis of 149 patients diagnosed with carcinoma of unknown
      primary site revealed that the liver was the organ with the highest frequency of
      metastases (33.5%). The objective response rates to chemotherapy were ~30.2%.
      Notably, ECOG was an important predictor of response to chemotherapy (P=0.008).
      The median progression-free survival was 7.1 months. Upon multivariate analysis,
      the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status was
      observed as an independent predictor of progression (P<0.0001). The median
      overall survival was 14.2 months. The ECOG was also an independent predictor of
      mortality (P<0.0001). In conclusion, the data from the present study have
      demonstrated that ECOG is an independent predictor of a poor response to
      chemotherapy, lower overall survival and progression-free survival in carcinoma
      of unknown primary site.

PMID- 28515922
TI  - Primary primitive neuroectodermal tumor of the cervix: A report of two cases and
      review of the literature.
AB  - Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri is
      extremely rare. Two cases of PNET of the cervix are presented herein. Two female
      patients, aged 48 and 43 years, presented with irregular uterine bleeding over
      the course of 1 year, and increased urinary frequency for 1 month, respectively.
      On gynecological examination, a mass in the cervix was palpated and a biopsy
      performed. The findings of the initial biopsy revealed small-cell carcinoma in
      both patients. Following neoadjuvant chemotherapy and radiotherapy, radical
      hysterectomy was performed in both patients. One patient received 5 courses of
      consolidation chemotherapy and postoperative radiotherapy, whereas the other
      patient received 1 course of consolidation chemotherapy. At the time of the
      article submission, both patients remained disease-free at 27 and 12 months,
      respectively, after their initial diagnosis. Only a limited number of cases of
      PNET of the cervix uteri have been reported in the literature to date. Multimodal
      therapies, including total excision, adjuvant chemotherapy and/or radiotherapy,
      have been adopted to treat patients with PNET of the cervix.

PMID- 28515918
TI  - Synchronous primary malignant neoplasms of the cervix and endometrium.
AB  - Synchronous multiple malignant neoplasms of the female genital tract are rare,
      particularly in the uterus. We herein present the case of a patient with
      synchronous cervical squamous epithelial carcinoma and endometrial
      adenocarcinoma, and discuss the diagnosis, treatment and prognosis. The patient
      underwent a cervical biopsy and fractional curettage of the endometrium, followed
      by abdominal staging surgery, including radical hysterectomy, bilateral salpingo
      oophorectomy, pelvic and para-aortic lymphadenectomy. The diagnosis was stage Ib1
      cervical cancer and stage Ia endometrial cancer, without lymph node metastases.
      There has been no recurrence during 1 year of followup. Synchronous genital tract
      neoplasms are more clinically complex compared with single neoplasms and it is
      crucial to focus on the differential diagnosis between primary and metastatic
      tumors during the diagnostic process. The treatment of synchronous genital tract
      neoplasms also differs significantly from that of single neoplasms, although the
      prognosis of patients with synchronous gynecological malignancies does not appear
      to be worse.

PMID- 28515921
TI  - Association between periodontitis and prognosis of pancreatobiliary tract cancer:
      A pilot study.
AB  - Several studies have indicated that periodontitis is a risk factor for cancer.
      However, the association between periodontitis and the prognosis of
      pancreatobiliary tract cancer remains unclear. The aim of this pilot study was to
      investigate the association between periodontitis and prognosis of
      pancreatobiliary tract cancer. A total of 22 patients diagnosed with
      pancreatobiliary tract cancer were analyzed. Oral health status, including
      severity of periodontitis, general health status and biochemical serum markers
      were evaluated. The Kaplan-Meier method and Cox proportional hazards model were
      used to assess factors affecting the prognosis of pancreatobiliary tract cancer.
      The Kaplan-Meier analysis demonstrated that low body mass index, high
      concentration of serum C-reactive protein (CRP) and severe periodontitis were
      significant prognostic factors for survival rate. The Cox proportional hazards
      model revealed that serum carbohydrate antigen 19-9 concentration [hazard ratio
      (HR)=1.002; 95% confidence interval (CI): 1.000-1.004] and serum CRP
      concentration (HR=2.57; 95% CI: 1.15-5.74) were significantly associated with the
      prognosis of pancreatobiliary tract cancer. In addition, cancer patients with
      severe periodontitis had higher serum CRP concentrations compared with those
      without severe periodontitis. Therefore, severe periodontitis indirectly affected
      the prognosis of pancreatobiliary tract cancer through promoting systemic
      inflammation.

PMID- 28515917
TI  - Total laparoscopic hysterectomy for large uterine cervical myoma.
AB  - Ureterolysis is a surgical method with a high level of difficulty, which may be
      necessary when performing total laparoscopic hysterectomy (TLH) for large
      cervical myoma, despite the benign nature of this tumor. The aim of the present
      study was to introduce techniques that are commonly applied in malignant tumor
      surgery in order to safely perform TLH for large cervical myoma. Between 2014 and
      2016, TLH was performed at the Shimane University Hospital (Izumo, Japan) in 153
      patients with benign tumors, including 25 cases with a large uterus (uterine
      weight >=500 g). The surgical methods applied in 3 of these large uterine
      cervical myoma cases were investigated in detail, including techniques devised by
      our department. TLH was performed without enucleating myomectomy in all 3 cases;
      however, all 3 cases required ureterolysis, transection of the anterior layer of
      the vesicouterine ligament and isolation of the ureter. In conclusion, although
      radical laparoscopic hysterectomy is commonly performed for cervical cancer at
      our department, techniques used for malignant tumor surgery may prove useful for
      benign cases with a high level of difficulty.

PMID- 28515913
TI  - Promoter polymorphisms of the vascular endothelial growth factor gene are
      associated with metabolic syndrome susceptibility in Koreans.
AB  - Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis.
      Patients with metabolic syndrome (MetS) have elevated plasma VEGF levels. The aim
      of the present study was to investigate the association between promoter
      polymorphisms (the -2578C>A and -1154G>A) of the VEGF gene and MetS
      susceptibility. A total of 640 subjects were enrolled in the study including 320
      patients with MetS and 320 healthy controls. Genotyping of the VEGF single
      nucleotide polymorphisms was performed by polymerase chain reaction-restriction
      fragment length polymorphism analysis. The CA and AA genotypes of the -2578C>A
      polymorphism were associated with decreased risk of MetS (P=0.018, P=0.003,
      respectively). For the -1154G>A polymorphism, although the GA genotype was more
      significantly frequent in MetS patients (P=0.022), the AA genotype and recessive
      model (GG+GA vs. AA) were protective against MetS susceptibility (P=0.016, 0.007,
      respectively). The A-G haplotype frequency composed of the -2578C>A and -1154G>A
      polymorphisms also differed between the 2 groups (P=0.011). The presented data
      suggested that the A alleles and A-G haplotype of the VEGF -2578C>A and -1154G>A
      polymorphisms are associated with decreased MetS susceptibility. To the best of
      the authors' knowledge, the current study is the first to investigate the
      associations between the VEGF -2578C>A and -1154G>A polymorphisms and MetS
      patients. Further evaluation is necessary to explore the associations between the
      VEGF polymorphisms and MetS patients in larger samples of other ethnic or racial
      populations.

PMID- 28515911
TI  - Expression of tubulin folding cofactor B in mouse hepatic ischemia-reperfusion
      injury.
AB  - The aim of the present study was to investigate the association between tubulin
      folding cofactor B (TBCB) expression and ischemia-reperfusion injury (IRI) in
      mice. A total of 48 C57BL/6 mice were randomly divided into a control group
      (Sham, n=6) and an ischemia-reperfusion group (n=42). The ischemia-reperfusion
      group was further divided into 6 subgroups as per different times after
      reperfusion (2, 4, 6, 8, 12 and 24 h), with 7 mice per subgroup. A hepatic IRI
      model was established in mice by clamping the hepatic hilum. Morphology, serum
      levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the
      expression level of TBCB were detected. Compared with the control group, the
      livers from the ischemia-reperfusion group were significantly changed,
      particularly at 12 h following ischemia-reperfusion, with obvious hepatic cell
      degeneration and necrosis. The ALT, AST, IL-6 and TNF-alpha levels in the sera of
      the mice in the hepatic ischemia-reperfusion group were increased at all time
      points following ischemia-reperfusion, and were the highest at 12 h,
      demonstrating statistically significant differences when compared with the
      control group (P<0.05). Furthermore, the expression levels of TBCB, TNF-alpha and
      IL-6 were significantly increased at all time-points following ischemia
      reperfusion, and were the most significant at 12 h. At 24 h following ischemia
      reperfusion, the expression levels had decreased. The present study indicated
      that TBCB expression is associated with TNF-alpha and IL-6 expression levels in
      mice with hepatic ischemia-reperfusion, and may be key in the development of
      liver injury during ischemia-reperfusion in mice.

PMID- 28515914
TI  - Analysis of the function of microRNA-375 in humans using bioinformatics.
AB  - MicroRNA-375 (miR-375) is expressed at low levels in many types of solid tumor,
      particularly in gastrointestinal tumors. It is considered to be important in the
      development of cancer and certain diseases. Thus, more detailed knowledge is
      required on the particular functions of miR-375. miRs function by regulating
      target genes. Therefore, in the current study, miRWalk (which includes the data
      from 10 prediction software programs) was used to predict the target genes of miR
      375. The genes, which were co-predicted using five different software programs
      were further analyzed using Database for Annotation, Visualization and Integrated
      Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) pathway analysis]. Subsequently, the online tool, Search
      Tool for the Retrieval of Interacting Genes, was used to analyze the protein
      protein interaction and construct modules using Cytoscape. The result
      demonstrated 6,574 predicted genes, 1,325 of which were co-predicted. The GO
      analysis result indicated that, in biological processes, the co-predicted genes
      were significantly enriched in the regulation of nervous system development and
      cell differentiation, and the highest enrichment of molecular function was ion
      binding. In KEGG analysis, the genes were enriched in the Hippo signaling
      pathway, glutamatergic synapse, circadian entrainment and the phosphoinositide 3
      kinase (PI3K)-Akt signaling pathway. The top 10 hub proteins were mechanistic
      target of rapamycin, PH domain and leucine rich repeat protein phosphatase 1,
      ubiquitously transcribed tetratricopeptide repeat containing, Y-linked, histone
      deacetylase 2, F-box and leucine rich repeat protein 19, KIT proto-oncogene
      receptor tyrosine kinase, angiotensinogen, Janus kinase 2, fibroblast growth
      factor 2 and RNA polymerase II subunit A. These proteins predominantly regulate
      the development and progression of cancer, hypertension, essential
      thrombocythemia and inflammation. The genes in the top seven modules selected
      were identified to be primarily enriched in chemokines, extracellular matrix
      receptor interaction, focal adhesion, the PI3K-Akt signaling pathway, amoebiasis
      and protein processing signaling pathway. Thus, the target genes and hub proteins
      that were predicted in the current study were identified to be important in
      regulating the development and progression of cancer and certain diseases.
      Furthermore, they present potential novel biomarkers for tumor diagnosis and
      candidate targets for treatment, and indicate that further research is required
      to establish the functions of miR-375.

PMID- 28515915
TI  - Superior effects of quetiapine compared with aripiprazole and iloperidone on MK
      801-induced olfactory memory impairment in female mice.
AB  - Cognitive dysfunction is commonly observed in schizophrenic patients and the
      administration of antipsychotic treatments results in different outcomes.
      Although the typical antipsychotic treatments, such as haloperidol, appear to be
      unable to improve cognition dysfunction, the atypical antipsychotic drugs
      (quetiapine, aripiprazole and iloperidone) exert a beneficial effect. The purpose
      of the current study was to investigate the effects of atypical antipsychotics on
      olfactory memory in mice, utilizing the social transmission of food preference
      (STFP) tests to evaluate the effects of drugs on MK-801-induced cognitive
      dysfunction. Female BALB/c mice were treated with quetiapine (5 and 10 mg/kg),
      aripiprazole (3 and 6 mg/kg), iloperidone (0.5 and 1 mg/kg) or MK-801 (0.1 mg/kg)
      alone or concurrently prior to retention sessions of STFP tests. In the STFP
      tests, quetiapine (10 mg/kg; P<0.05), aripiprazole (3 and 6 mg/kg; P<0.01 and
      P<0.001, respectively), iloperidone (0.5 and 1 mg/kg; P<0.01 and P<0.001,
      respectively) and MK-801 (P<0.001) significantly decreased cued/total food eaten
      (%). Quetiapine (5 mg/kg; P<0.05) significantly increased MK-801-induced
      decreases in cued/total food eaten (%), while aripiprazole and iloperidone
      demonstrated no significant effects. The results revealed that all of the drugs
      disturbed olfactory memory in the naive mice; however, only quetiapine reversed
      MK-801-induced memory impairment in the STFP test.

PMID- 28515920
TI  - Predictive value of the modified Glasgow Prognostic Score for the therapeutic
      effects of molecular-targeted drugs on advanced renal cell carcinoma.
AB  - Inflammation is considered to be a prognostic factor for renal cell carcinoma
      (RCC). An inflammation-based prognostic score (modified Glasgow Prognostic Score;
      mGPS) is widely used for preoperative patients; however, little information is
      available regarding its prognostic value in patients with RCC treated with
      molecular-targeted drugs. A total of 32 advanced and recurrent RCC patients
      initially treated with molecular-targeted drugs from October, 2009 to August,
      2015 were retrospectively investigated. Information on patient characteristics
      prior to treatment initiation and the clinical course were retrieved from
      clinical records. The correlation between survival and patient variables was
      analyzed. Survival was compared among patient groups according to the mGPS score.
      The median patient age was 66 years. The percentage of patients with an Eastern
      Cooperative Oncology Group performance status of 0 or 1 was 87.5, and 65.6% of
      the RCCs were clear cell carcinomas. A Memorial Sloan-Kettering Cancer Center
      index of good or intermediate was determined for 75% of the patients. Sunitinib,
      pazopanib or sorafenib was administered to 56, 22 and 13% of the cases,
      respectively. An mGPS score of 0, 1 and 2 was calculated for 66, 9 and 25% of the
      cases, respectively. Patients in the mGPS low group (score 0) exhibited
      significantly better progression-free survival (PFS) and overall survival (OS)
      compared with patients in the mGPS high group (score 1 or 2) (median PFS, 307 vs.
      70 days and median OS, 1,081 vs. 140 days, respectively). In conclusion,
      inflammatory status as assessed by the mGPS score was closely associated with the
      prognosis of RCC patients treated with molecular-targeted therapy.

PMID- 28515923
TI  - Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical
      approach.
AB  - C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal
      cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is
      involved in lymphocyte trafficking. Recent studies have demonstrated that, during
      pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a
      key role in suppressing the maternal T-cell response against the fetus. In the
      present study, the significance of CXCR4 and IDO expression in human colorectal
      cancer (CRC) has been investigated by immunohistochemical assay, and their
      association with survival was analyzed. Tumor specimens (n=60) from patients with
      different American Joint Committee on Cancer (AJCC) stages of CRC (I or IV) were
      assessed. In the stage IV group, 23 of 30 cases (77%) stained positive for CXCR4,
      and 9 of 30 (30%) were positive for IDO. By contrast, in the stage I group, 7 of
      30 cases (23%) stained positive for CXCR4, and 15 of 30 cases (50%) were positive
      for IDO. The 5-year survival rate of those with high CXCR4 expression in tumor
      specimens (n=30) was significantly worse compared with those with negative CXCR4
      expression (16.3 vs. 60.7%, P=0.02). By contrast, the 5-year survival rate of
      those with high IDO expression in tumor specimens (n=24) was not significantly
      different compared with those with negative IDO expression (36.4 vs. 56.8%). In
      the stage I group, 4 patients in the high IDO expression group (n=15) had distant
      metastases (2 in the liver 1 in the brain, and 1 in the lung). Taken together,
      CXCR4 appears to be a novel predictive indicator of survival, and IDO expression
      in the early stage may be a predictor of distant metastasis.

PMID- 28515919
TI  - Programmed death-ligand 1 expression is associated with fibrosarcomatous
      transformation of dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a locally invading tumor, characterized
      by the presence of the collagen type I alpha 1 (COL1A1)-platelet-derived growth
      factor (PDGF) beta fusion gene. We herein report the case of a 31-year-old man
      with a history of resection of an abdominal wall DFSP. The patient presented with
      chest pain and a computed tomography scan revealed a large mass in the posterior
      mediastinum and another mass in the right lung. The mediastinal mass was a
      sarcomatous lesion expressing the COL1A1-PDGFbeta fusion gene, suggesting that it
      represented a metastasis of the DFSP following fibrosarcomatous (FS)
      transformation. Following resection of the mediastinal metastasis and subsequent
      radiotherapy, the mass in the right lung was also resected. Due to the emergence
      of pleural and pancreatic tail metastases, the patient was treated with a
      combination therapy of adriamycin and ifosfamide. After five courses, the disease
      progressed and the patient was subsequently treated with pazopanib for ~2 months
      until further progression. Three years after the diagnosis of the mediastinal
      metastasis of DFSP, the patient was referred to another hospital for palliative
      care. The expression of programmed cell death 1 ligand (PD-L1) in the primary and
      metastatic tumors was investigated: PD-L1 expression was detected in the
      metastasis but not in the primary tumor. Given that the metastatic tumor
      exhibited FS transformation (DFSP-FS), PD-L1 expression may be induced by FS
      transformation, contributing to the metastasis through escape from immune
      surveillance. Further investigation of the PD-L1 pathway in DFSP and DFSP-FS in
      primary as well as metastatic sites is required to evaluate the clinical efficacy
      of therapies targeting the PD-L1 signaling cascade.

PMID- 28515925
TI  - Nipple-sparing mastectomies: Clinical outcomes from a single academic
      institution.
AB  - Nipple-sparing mastectomies (NSMs) are increasingly used in the surgical
      treatment of patients with breast cancer and for prevention of breast cancer. The
      present study was performed to review the outcomes of patients undergoing NSMs at
      a single large university setting. A retrospective chart review was performed on
      all patients undergoing NSMs from 2008-2014. Charts were reviewed for demographic
      data and patient characteristics. Tumor and breast size, cancer recurrence and
      complications were also evaluated. Descriptive statistics were utilized to
      summarize the findings. From 2008-2014, 110 patients underwent 197 NSMs. The mean
      patient age was 44.4 years (range, 20-77). The average body mass index was 24
      (range, 18-47). Breast weight was available for 106 specimens, with a mean weight
      of 475.5 g (range, 124.1-1,625.0 g). Seventy-three NSMs were performed for cancer
      and 124 were performed prophylactically. The mean tumor width was 1.38 cm (range,
      0-6.0 cm), with an average nipple to tumor distance of 5.87 cm (range, 2.93-10.0
      cm). Three (4%) patients required removal of the nipple areolar complex (NAC) due
      to pathological extension of the tumor. A total of 34 (17.2%) complications
      occurred, including infections, hematomas and nipple necrosis, with 9 requiring
      removal of the NAC and 13 requiring removal of the tissue expander or implant.
      Smokers had a 36.0% (9/25) complication rate, compared with 14.5% (25/172) of
      nonsmokers (P<0.05). During follow-up, one recurrence was noted, located on the
      chest wall. There were no recurrences in the NAC group. Therefore, NSMs may
      safely be performed without compromising oncologic outcomes or increasing
      complication rates in properly selected patients.

PMID- 28515926
TI  - Cisplatin-based chemoradiotherapy with 5-fluorouracil or pemetrexed in patients
      with locally advanced, unresectable esophageal squamous cell carcinoma: A
      retrospective analysis.
AB  - Treatment with 5-fluorouracil (5-FU) and cisplatin (PF regimen) remains the most
      frequently used chemotherapy for esophageal squamous cell carcinoma (SCC). The
      aim of the present study was to assess the efficacy and safety of
      pemetrexed/cisplatin (PP regimen) as definitive treatment compared with PF. A
      total of 60 patients with locally advanced, unresectable SCC of the esophagus
      receiving concomitant chemoradiotherapy were recruited in this study; of those
      patients, 29 received four cycles (two concomitant and two post-radiotherapy) of
      the PF regimen (arm A, cisplatin 25 mg/m2/day i.v. on days 1-3 plus 5-FU 800
      mg/m2/24 h by continuous infusion on days 1-5) and 31 received four cycles of the
      PP regimen (arm B, cisplatin 25 mg/m2/day i.v. on days 1-3 plus pemetrexed 500
      mg/m2 on day 1). All the patients in both arms received a total radiation dose of
      59.6 Gy. The two arms were well-matched for age, gender, Karnofsky performance
      status, TNM stage, tumor location and length. The overall response rate was 89.7%
      in arm A vs. 93.5% in arm B (P>0.05). The median overall survival was 26.1 months
      [95% confidence interval (CI): 15.3-36.8 months] in arm A vs. 28.7 months (95%
      CI: 9.4-48.0 months) in arm B (P>0.05). Severe esophagitis occurred in 31.0%
      (9/29) of the patients in arm A vs. 12.9% (4/31) of the patients in arm B; the
      difference was statistically significant (P=0.036). Grade 3/4 leukopenia and
      thrombocytopenia occurred in 4 (13.8%) and 1 (3.4%) patients, respectively, in
      arm A vs. 12 (38.7%) and 6 (19.4%) patients, respectively, in arm B; the
      differences were statistically significant (P=0.029 and 0.041, respectively).
      Therefore, chemoradiotherapy with the PP regimen achieved therapeutic results
      comparable with those of the PF regimen; in terms of toxicity, the incidence of
      hematological toxicity was higher and that of esophagitis was lower with the PP
      regimen.

PMID- 28515924
TI  - Effect of serum interleukin-1 receptor antagonist level on survival of patients
      with non-small cell lung cancer.
AB  - Due to poor prognosis in advanced non-small cell lung cancer (NSCLC), new
      effective markers are required in the monitoring of the disease. The present
      study aimed to investigate the association between the serum IL-1 receptor
      antagonist (IL-1Ra) level, overall survival (OS), and treatment response in
      NSCLC, and to evaluate the usefulness of the serum IL-1Ra level as a prognostic
      marker for NSCLC. Eighty patients (72 men and 8 women) and 40 healthy volunteers
      (13 men and 27 women) were included in the present study. The median progression
      free survival was 16 weeks for patients with high serum IL-1Ra levels, and 35
      weeks for patients with low serum IL-1Ra levels (P=0.027). The median OS was 38
      weeks in patients with a high serum IL-1Ra level, and 62 weeks in patients with a
      low serum IL-1Ra level (P=0.065). The results of the present study have
      demonstrated that there was a significant correlation between IL-1Ra levels and
      NSCLC progression and survival, although the correlation between IL-1Ra levels
      and the response to treatment was not statistically significant. Therefore, the
      pre-treatment IL-1Ra level has been identified as a putative prognostic factor
      for NSCLC.

PMID- 28515927
TI  - Body mass index as a classifier to predict biochemical recurrence after radical
      prostatectomy in patients with lower prostate-specific antigen levels.
AB  - Prostate cancer, one of the most common malignant tumors among men, is closely
      associated with obesity and, thus far, several studies have suggested the
      association between obesity and aggressive pathological characteristics in the
      United States. However, the effect of obesity on prostate cancer mortality is
      controversial, and it remains unclear whether obesity contributes to the
      aggressiveness of prostate cancer in Asian patients. The aim of the present study
      was to investigate the association between body mass index (BMI) and the
      clinicopathological characteristics of prostate cancer in 2,003 Japanese patients
      who underwent radical prostatectomy. There was a significant association between
      higher BMI and higher Gleason score (GS). The multivariate analysis also revealed
      that BMI was an independent indicator for GS >=8 at surgery. Moreover, among
      patients with lower prostate-specific antigen levels, biochemical recurrence-free
      survival was significantly worse in those with higher BMI. These results suggest
      that BMI may be a classifier for predicting adverse pathological findings and
      biochemical recurrence after radical prostatectomy in Japanese patients.

PMID- 28515928
TI  - Single-institutional experience of clinicopathological analysis and treatment for
      lung cancer patients with human immunodeficiency virus infection.
AB  - The advent of antiretroviral therapy has changed the disease spectrum
      constitution among patients living with human immunodeficiency virus (HIV), while
      the incidence of death due to non-AIDS-defining cancers, particularly lung
      cancer, continues to increase in the USA and Europe. However, the availability of
      detailed reports of the clinical characteristics of lung cancer among Asian
      populations is limited. The present study retrospectively analyzed the clinical
      characteristics, treatment regimens and outcomes of lung cancer patients with HIV
      who were treated in a single institution between 1988 and 2013. Of the 20 lung
      cancer patients living with HIV included in this study, 90% were diagnosed since
      1996 in the post-antiretroviral era. The median CD4+ cell count was 373.5/ul,
      whereas 65% of the patients were diagnosed with adenocarcinoma and 30% with
      squamous cell carcinoma. Epidermal growth factor receptor mutations were detected
      in 3 (27%) of the 11 specimens for which data were available, of which 65% had
      advanced-stage disease. Of the 20 patients, 9 underwent surgery, 6 received
      radiotherapy and 5 received chemotherapy as a first-line treatment. Treatment was
      generally well-tolerated. The median survival period was 35.8 months for all
      stages and 14.0 months for advanced stages. The treatment outcomes in our
      institution were favorable in comparison with previous studies from the USA and
      Europe, although these findings may be due to ethnic differences or the efficacy
      of treatment for HIV and lung cancer.

PMID- 28515930
TI  - Determination of adequate pelvic lymph node dissection range for Japanese males
      undergoing radical prostatectomy.
AB  - The present study aimed to determine the adequate pelvic lymph node dissection
      (PLND) range for Japanese males undergoing radical prostatectomy. A total of 467
      Japanese patients who underwent antegrade radical prostatectomy at the National
      Kyushu Cancer Center (Fukuoka, Japan) were retrospectively reviewed. The patients
      were divided into two groups according to the PLND extent: The standard
      (obturator + internal iliac nodes) group and the expanded (standard + additional
      nodes) group, which accounted for 64.5% (301/467) and 35.5% (166/467) of the
      patients, respectively. No differences were observed in the preoperative and
      postoperative characteristics of the two groups. In addition, there was no
      difference in PSA recurrence between the two groups. There were no differences
      between the standard and expanded groups in the low-, intermediate- and high-risk
      groups (P=0.1456, P=0.1581, P=0.2125, respectively). The median number of lymph
      node dissection was 13 and 19, in the standard and expanded groups respectively
      (P<0.0001). However, regarding the number of lymph node metastases and the rate
      of patients with lymph node metastasis, no significant difference was observed
      between the standard and expanded groups (P=0.4219 and P=0.4257, respectively).
      According to multivariate analysis, a significant difference in the presence of
      lymph node metastasis (hazard ratio 3.547; P=0.0247), but not in the PLND extent,
      was detected in patients with prostate specific antigen failure (P=0.0655). When
      expanding the dissection extent, the number of dissected lymph nodes increases,
      but is not associated with the number or rate of positive lymph nodes. Thus, the
      current dissection range is considered to be appropriate for Japanese men
      undergoing radical prostatectomy.

PMID- 28515929
TI  - Clinical outcome of posterior fixation surgery in patients with vertebral
      metastasis of lung cancer.
AB  - Vertebral metastasis of non-small-cell lung cancer (NSCLC) often leads to
      neurological paralysis, with deterioration of the patients' activities of daily
      living (ADL). Surgical treatments for the symptoms are unlikely to be recommended
      due to the poor prognosis of patients with advanced NSCLC. The aim of the present
      study was to retrospectively evaluate the clinical outcome of posterior spinal
      fixation surgery in patients with neurological paralysis resulting from vertebral
      metastasis of NSCLC. Between April, 2007 and March, 2012, 4 patients (3 men and 1
      woman; median age, 56.5 years) underwent fixation surgery at the Shiga University
      of Medical Science Hospital (Otsu, Japan). The mean preoperative Tokuhashi and
      Tomita scores of the patients were high (8.25 and 7.0, respectively). However,
      the Frankel grade functional score and performance status of the patients
      improved following fixation surgery, after which all patients received
      chemoradiotherapy. Postoperatively, the median paralysis-free time was 41 months
      (range, 17-42 months) and the median survival time was 42.5 months (range, 22-43
      months). According to the functional scores, the patients had a poor prognosis,
      which may have been a contraindication for fixation surgery. In these cases,
      however, surgical treatment improved the patients' ADL and increased the
      likelihood of receiving anticancer therapy, contributing to the prolongation of
      survival. Therefore, fixation surgery may be beneficial for patients with
      neurological paralysis following vertebral metastasis of advanced NSCLC.

PMID- 28515931
TI  - Pharmaco-economic analysis of adjuvant chemotherapy for stage II and III
      colorectal cancer.
AB  - Comparison of the costs of capecitabine plus oxaliplatin (CapeOX) with that of
      FOLFOX6 (5-fluorouracil/leucovorin [LV] + oxaliplatin) as an adjuvant
      chemotherapy for stage II or III colorectal cancer has previously been reported.
      However, there are no reports comparing uracil and tegafur (UFT)/LV with
      capecitabine. Therefore, the current study compared the costs of adjuvant
      chemotherapy regimens including CapeOX, FOLFOX6, capecitabine and UFT/LV. The
      costs of chemotherapeutic drugs and for the prevention and treatment of adverse
      events were evaluated, as these account for the bulk of the treatment costs.
      Costs were expressed in Japanese Yen (US dollars). The mean costs of the
      chemotherapeutic drugs per patient, for an entire course of treatment, were
      Y882,632 ($8,406) for UFT/LV, Y353,290 ($3,365) for capecitabine, Y1,436,218
      ($13,678) for FOLFOX6 and Y1,255,630 ($11,958) for CapeOX. The mean costs
      associated with adverse events per patient were Y2,210 ($21) for UFT/LV, Y6,749
      ($64) for capecitabine, Y173,432 ($1,652) for FOLFOX6 and Y107,430 ($1,023) for
      CapeOX. Therefore, the capecitabine regimen contributes to reducing costs for the
      management of patients with colorectal cancer who have had surgery.

PMID- 28515932
TI  - Single-stage laparoscopic adrenalectomy for pheochromocytoma and enucleation of a
      pancreatic neuroendocrine tumor in Von Hippel-Lindau disease: A case report.
AB  - Von Hippel-Lindau (VHL) disease is an inherited syndrome with autosomal-dominant
      transmission, characterized by central nervous system and retinal
      hemangioblastomas, visceral cysts and tumors. Optimal surgical treatment,
      including its timing, remains a controversial topic. The present study reports
      the case of a 67-year-old female patient with adrenal and pancreatic
      manifestations of VHL. A laparoscopic cortex-sparing left adrenalectomy for a 4
      cm pheochromocytoma and pancreatic enucleation for pancreatic polypeptidoma of
      the pancreas tail were performed during the same operative procedure. The total
      operative time was 240 min. There were no operative complications, and the
      surgery was completed laparoscopically with minimal blood loss. A prolonged
      hospital stay was necessary to treat a grade C postoperative pancreatic fistula.
      The histopathological result was an adrenal pheochromocytoma and a well
      differentiated neuroendocrine tumor, secreting pancreatic polypeptides. In
      conclusion, organ-sparing laparoscopic surgery is an important option for
      treating simultaneous lesions in several abdominal solid viscera, such as VHL
      disease, and the present case study represents, to the best of the authors'
      knowledge, the first report of single-stage laparoscopic adrenalectomy and
      pancreatic tumor enucleation.

PMID- 28515933
TI  - Evaluation of a multiprofessional, nonsurgical obesity treatment program: which
      parameters indicated life style changes and weight loss?
AB  - BACKGROUND: According to the current evidence, behavior modifications are an
      effective part of a non-surgical multiprofessional obesity treatment program
      (MOTP). The purpose of the present study was to report changes in weight as well
      in psychological variables during a one year MOTP. We aimed to identify the
      associations of emotional state and patients' emotion regulation skills with
      weight change. METHODS: Prospective interventional study. Data of participants
      attending the one year obesity treatment in either a group or individual
      structured MOTP were analyzed. Weight, BMI (Body Mass Index) and measures on
      psychosomatic variables, emotion regulation skills, affective state, shame and
      guilt were collected at baseline, after three months and after one year. Mixed
      effects models were used for the statistical analysis of BMI. RESULTS: We
      included 238 patients at baseline (t1), 234 after three months (t2) and 179 after
      one year (t3). A drop in BMI measurements of at least 5% was observed in 20.6% of
      participants at t2 and 41.4% of participants at t3. After three months,
      participants showed significant improvements in the following psychosomatic
      variables: somatisation (p < 0.001), interpersonal sensitivity (p < 0.001),
      emotion regulation skills (p < 0.01), and attention to emotions (p < 0.05). Most
      of the improvements could be maintained after one year. BMI reduction was
      associated with a positive change in emotions, improvements in emotion regulation
      skills, and a reduction of depressive symptoms, disgust and shame. CONCLUSIONS:
      The results indicate that the assessment and treatment of psychological aspects
      like depression, emotion regulation skills, body awareness, and acceptance should
      be a vital part of an interdisciplinary MOPT. TRIAL REGISTRATION: Ethical
      approval for the present study was obtained from the Bern Kantonal Ethics
      Committee (KEK-Bern-Study Nr 258/14), Bern, Switzerland.

PMID- 28515934
TI  - Zolpidem prescribing practices before and after Food and Drug Administration
      required product labeling changes.
AB  - BACKGROUND: Women have higher morning serum zolpidem concentrations than men
      after taking an evening dose, potentially leading to increased risk of harm. On
      19 April 2013, the United States Food and Drug Administration required labeling
      changes for zolpidem, recommending an initial dose of no greater than 5 mg
      (immediate release) or 6.25 mg (controlled release) per night in women.
      OBJECTIVES: The primary objective of this study was to compare prescribing
      practices before and after the 2013 zolpidem labeling change. A secondary
      objective was to evaluate serious adverse events potentially related to zolpidem.
      METHODS: Electronic medical records of adults receiving care through the
      University of Colorado Health system were accessed for study inclusion if
      patients were provided a first-time prescription for zolpidem either prior to or
      after the Food and Drug Administration labeling change. Patients were randomly
      chosen from eight strata based on age, gender, and date of zolpidem initiation
      (before/after the labeling change). Demographic and zolpidem prescribing data
      were collected. Low-dose zolpidem was considered 5 mg (immediate release) or 6.25
      mg (controlled release) daily or less. Documentation of potentially related
      serious adverse events within the patients' records was also evaluated. RESULTS:
      A total of 400 patients were included in the study. The overall percentage of
      patients prescribed low-dose zolpidem increased from 44% to 58% after the
      labeling change (p = 0.0020). In a pre-specified subgroup analysis, the
      percentage of patients prescribed low-dose zolpidem increased in all groups,
      including young men (38%-50%, p = 0.23), elderly men (34%-40%, p = 0.53), and
      elderly women (60%-74%, p = 0.14), but the change was only significant in young
      women (42%-70%, p = 0.0045). CONCLUSION: After Food and Drug Administration
      mandated labeling changes for zolpidem in 2013, the percentage of overall
      patients in our health system, and specifically young women, with initial
      prescriptions for low-dose zolpidem significantly increased as compared to before
      the labeling change.

PMID- 28515935
TI  - Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered
      with pathophysiologically based therapy.
AB  - BACKGROUND/OBJECTIVES: Neurotoxicity is a serious and sometimes fatal adverse
      effect that can occur following methotrexate treatment. We describe two adult
      patients with hematological malignancies with methotrexate encephalopathy who
      recovered with dextromethorphan therapy. RESULTS: Case 1: A 24-year-old male with
      acute lymphoblastic leukemia developed the acute onset of bilateral facial
      weakness and slurred speech after his first treatment with high-dose intravenous
      methotrexate. The clinical scenario and a head magnetic resonance imaging
      supported a diagnosis of methotrexate encephalopathy. Treatment with
      dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with
      recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous
      methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked
      lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of
      starting dextromethorphan, there was improvement with clinical recovery.
      CONCLUSIONS: These two cases suggest that N-methyl d-aspartate receptor
      activation by homocysteine may play an important role in the pathogenesis of
      methotrexate neurotoxicity.

PMID- 28515669
TI  - Suppression and azimuthal anisotropy of prompt and nonprompt [Formula: see text]
      production in PbPb collisions at [Formula: see text][Formula: see text].
AB  - The nuclear modification factor [Formula: see text] and the azimuthal anisotropy
      coefficient [Formula: see text] of prompt and nonprompt (i.e. those from decays
      of b hadrons) [Formula: see text] mesons, measured from PbPb and pp collisions at
      [Formula: see text] [Formula: see text] at the LHC, are reported. The results are
      presented in several event centrality intervals and several kinematic regions,
      for transverse momenta [Formula: see text] [Formula: see text] and rapidity
      [Formula: see text], extending down to [Formula: see text] [Formula: see text] in
      the [Formula: see text] range. The [Formula: see text] of prompt [Formula: see
      text] is found to be nonzero, but with no strong dependence on centrality,
      rapidity, or [Formula: see text] over the full kinematic range studied. The
      measured [Formula: see text] of nonprompt [Formula: see text] is consistent with
      zero. The [Formula: see text] of prompt [Formula: see text] exhibits a
      suppression that increases from peripheral to central collisions but does not
      vary strongly as a function of either y or [Formula: see text] in the fiducial
      range. The nonprompt [Formula: see text] [Formula: see text] shows a suppression
      which becomes stronger as rapidity or [Formula: see text] increases. The
      [Formula: see text] and [Formula: see text] of open and hidden charm, and of open
      charm and beauty, are compared.

PMID- 28515936
TI  - Pulse dose steroids in severe pulmonary arterial hypertension secondary to
      systemic lupus erythematosus.
AB  - OBJECTIVE: The pulmonary vascular targeted treatment for systemic lupus
      erythematosus-associated pulmonary arterial hypertension is similar to other
      connective tissue disease-associated pulmonary arterial hypertension. In
      addition, there also appears to be a role for immunosuppression in the overall
      management. However, the optimal immunosuppressive regimen and what patients will
      respond to treatments are currently not clearly elucidated given the lack of
      randomized controlled trials on the subject. Our objective is to highlight the
      importance of early immunosuppression in systemic lupus erythematosus-associated
      pulmonary arterial hypertension and the role of pulse dose steroids in
      management. METHODS: This case describes a 23-year-old woman who presented with
      pulmonary arterial hypertension diagnosed by right heart catheterization with
      mean pulmonary artery pressure of 74 mmHg, pulmonary capillary wedge pressure of
      12 mmHg, and a pulmonary vascular resistance of 1908 dyne s cm-5. Due to the
      aggressive nature of her disease, she declined despite management with
      epoprostenol and sildenafil. Because of coexisting systemic lupus erythematosus
      with hemolytic anemia and worsening pulmonary arterial hypertension, intensive
      immunosuppressive therapy with pulse dose steroids was initiated. RESULTS:
      Shortly after initiation of pulse dose steroids and maintenance
      immunosuppression, she had a dramatic symptomatic and hemodynamic response with a
      decrease in her pulmonary vascular resistance from 1908 to 136 dyne sec cm-5 and
      improvement in her mean pulmonary artery pressure from 74 to 27 mmHg on repeat
      right heart catheterization. CONCLUSION: Early immunosuppression is important to
      consider in those with systemic lupus erythematosus-associated pulmonary arterial
      hypertension. Limited studies are available, but most have focused on the use of
      cyclophosphamide. Pulse dose steroids may be a potentially less toxic but equally
      effective manner to aid in the treatment of systemic lupus erythematosus
      pulmonary arterial hypertension when intensive immunosuppression is being
      considered.

PMID- 28515937
TI  - Dicyano- and tetracyanopentacene: foundation of an intriguing new class of easy
      to-synthesize organic semiconductors.
AB  - Cyanated pentacenes are very promising candidate materials for ambipolar and n
      type transistors. However, only a few examples have been obtained to date - all
      requiring lengthy, multi-step processes. Herein, we present the first preparation
      of 5,7,12,14-tetracyanopentacene (TCP) and a facile, scaled-up preparation of
      6,13-dicyanopentacene (DCP). Both compounds are prepared by a one-pot synthesis
      using cheap quinones as starting materials. Detailed crystallographic
      investigations evince that the bulk assemblies of both cyanated pentacenes are
      dominated by non-covalent interactions, resulting in a dense, stable, face-to
      face packing and in an intriguing packing motif for TCP. Very low frontier
      molecular orbital energy levels and a reversible bleaching of TCP are revealed by
      cyclic voltammetry. Finally, both cyanated pentacenes are used in proof-of
      concept organic thin-film transistors (OTFTs) operating under ambient conditions.
      This work highlights the potential of cyanation for larger acenes and presents a
      straightforward route to the rational design of this promising class of
      materials.

PMID- 28515938
TI  - Accounting for adjuvant-induced artifacts in the characterization of vaccine
      formulations by polyacrylamide gel electrophoresis.
AB  - OBJECTIVES: Several vaccine adjuvants comprise complex nano- or micro-particle
      formulations, such as oil-in-water emulsions. In order to characterize
      interactions and compatibility of oil-in-water emulsion adjuvants with protein
      antigens in vaccines, effective protein characterization methods that can
      accommodate potential interference from high concentrations of lipid-based
      particles are needed. METHODS: Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) is a standard protein characterization technique which
      is affected by the presence of adjuvants such as oil-in-water emulsions. In this
      article, we investigate variations in SDS-PAGE methods that result in a reduction
      of adjuvant-induced staining artifacts. We have investigated whether the SDS
      method or the adjuvant composition were the reason for these artifacts and
      succeeded in reducing the artifacts with a modified sample preparation and
      different staining procedures. RESULTS: The best results were obtained by using
      gold staining or silver staining instead of a Coomassie Blue staining procedure.
      Moreover, the replacement of the dilution buffer (20% SDS to disrupt emulsion) by
      alternative detergents such as Tween(r) 80 and Triton(r) X-100 removed adjuvant
      induced streaking artifacts at the top of the gel. CONCLUSIONS: These methods may
      be useful for improving characterization approaches of antigen-adjuvant mixtures
      by SDS-PAGE.

PMID- 28515666
TI  - Performance of algorithms that reconstruct missing transverse momentum in
      [Formula: see text]= 8 TeV proton-proton collisions in the ATLAS detector.
AB  - The reconstruction and calibration algorithms used to calculate missing
      transverse momentum ([Formula: see text] ) with the ATLAS detector exploit energy
      deposits in the calorimeter and tracks reconstructed in the inner detector as
      well as the muon spectrometer. Various strategies are used to suppress effects
      arising from additional proton-proton interactions, called pileup, concurrent
      with the hard-scatter processes. Tracking information is used to distinguish
      contributions from the pileup interactions using their vertex separation along
      the beam axis. The performance of the [Formula: see text] reconstruction
      algorithms, especially with respect to the amount of pileup, is evaluated using
      data collected in proton-proton collisions at a centre-of-mass energy of 8
      [Formula: see text] during 2012, and results are shown for a data sample
      corresponding to an integrated luminosity of [Formula: see text]. The simulation
      and modelling of [Formula: see text]  in events containing a Z boson decaying to
      two charged leptons (electrons or muons) or a W boson decaying to a charged
      lepton and a neutrino are compared to data. The acceptance for different event
      topologies, with and without high transverse momentum neutrinos, is shown for a
      range of threshold criteria for [Formula: see text] , and estimates of the
      systematic uncertainties in the [Formula: see text]  measurements are presented.

PMID- 28515941
TI  - Tissue-resident lymphocytes: sentinel of the transformed tissue.
AB  - Tumor cells can be detected and cleared by lymphocytes in a process termed cancer
      immunosurveillance. However, the contributing cell types had not been fully
      characterized. Using oncogene-induced murine models of epithelial cancer, a
      recent study showed that cell transformation triggers expansion of tissue
      resident lymphocytes derived from innate, T cell receptor (TCR) alphabeta and
      TCRgammadelta lineages. These type-1-like innate lymphoid cells (ILC1ls) and type
      1 innate-like T cells (ILTC1s) share a gene expression program distinct from
      those of conventional lymphocytes, and exhibit cytolytic activities against tumor
      cells. Further deciphering such a tumor-elicited immunosurveillance mechanism may
      1 day be harnessed for novel cancer immunotherapy.

PMID- 28515940
TI  - Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic
      ketoacidosis in a patient with metastatic lung cancer.
AB  - BACKGROUND: Advances in cancer immunotherapy have generated encouraging results
      in multiple malignancies refractory to standard chemotherapies. As the use of
      immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side
      effects associated with these agents, termed immune related adverse events
      (irAE), is expected to increase. The frequency of significant irAE in ICI treated
      patients is about 10-20% and early recognition is critical to prevent serious
      morbidity and even mortality. New onset autoimmune diabetes mellitus (DM)
      associated with immune checkpoint inhibitor treatment is extremely rare,
      occurring in less than 1% of patients. Autoimmune DM often presents as diabetic
      ketoacidosis, a medical emergency requiring immediate treatment. We describe the
      first reported case of a patient with lung cancer who developed autoimmune
      diabetes after nivolumab treatment and was found to have three diabetes related
      (islet) autoantibodies present before ICI treatment and seroconversion of another
      after ICI treatment and onset of autoimmune DM. CASE PRESENTATION: A 34 year old
      African American woman with metastatic non-small cell lung cancer (NSCLC) was
      treated with nivolumab in the second line setting after disease progression
      following standard chemoradiation therapy. After receiving two doses of
      nivolumab, the patient developed abrupt onset of hyperglycemia and diabetic
      ketoacidosis. Autoimmune diabetes was diagnosed on the basis of undetectable C
      peptide levels, seropositivity of three diabetes related (islet) autoantibodies
      and absolute insulin dependence. The patient eventually required use of
      continuous subcutaneous insulin infusion (insulin pump) due to erratic glycemic
      excursions and multiple readmissions for DKA. Human leucocyte antigen (HLA)
      genoyping revealed none of the high risk haplotypes associated with the
      development of type 1 diabetes. Interestingly, a frozen blood sample obtained
      prior to treatment with nivolumab tested positive for three of the four diabetes
      related (islet) autoantibodies despite no prior history of diabetes and no family
      history of diabetes. Notably, at the time of manuscript preparation, the patient
      is without evidence of NSCLC recurrence with no further treatment since the
      nivolumab therapy. CONCLUSION: New onset autoimmune diabetes mellitus associated
      with nivolumab has been described only in case reports and occurs at rates of <
      1% in the large clinical trials which garnered FDA approval in the second line
      setting for NSCLC. As ICI use continues to expand across a wide variety of
      malignancies, clinicians must maintain a high index of suspicion for irAE,
      including autoimmune DM and other endocrinopathies. A multidisciplinary team and
      thorough education of the patient are recommended to optimize management of new
      onset adult autoimmune DM. Our patient may have been at greater risk for the
      development of ICI related autoimmune diabetes due to the presence of three
      diabetes related autoantibodies prior to therapy; however, about half of the
      reported cases of autoimmune DM after anti-PD-1 therapy occurred in patients with
      no detectable diabetes related autoantibodies. Further studies are needed to
      delineate genetic and immunologic biomarkers that may be useful in identifying
      patients at risk of developing ICI related autoimmune DM.

PMID- 28515939
TI  - Vaccine against arteriosclerosis: an update.
AB  - Substantial data from experimental and clinical investigation support the role of
      immune-mediated mechanisms in atherogenesis, with immune systems responding to
      many endogenous and exogenous antigens that play either proatherogenic or
      atheroprotective roles. An active immunization strategy against many of these
      antigens could potentially alter the natural history of atherosclerosis. This
      review mainly focuses on the important studies on the search for antigens that
      have been tested in vaccine formulations to reduce atherosclerosis in preclinical
      models. It will also address the opportunities and challenges associated with
      potential clinical application of this novel therapeutic paradigm.

PMID- 28515943
TI  - Evaluation of dosing strategy for pembrolizumab for oncology indications.
AB  - BACKGROUND: Traditionally, most monoclonal antibodies (mAbs) have been dosed
      based on body weight because of perceived contribution of body size in
      pharmacokinetic variability. The same approach was used in the initial
      pembrolizumab studies; however, following availability of PK data, the need for
      weight-based dosing for pembrolizumab was reassessed. METHODS: A previously
      established population PK (popPK) model as well as exposure-response results from
      patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used
      to evaluate the potential application of a fixed dosing regimen with the aim of
      maintaining pembrolizumab exposures within the range demonstrated to provide near
      maximal efficacy and acceptable safety. Individual PK exposures for the selected
      fixed dosing regimen from recently completed trials with head and neck cancer,
      NSCLC, microsatellite instability high (MSI-H) in colorectal cancer (CRC) and
      urothelial cancer were used to confirm acceptability. To determine whether fixed
      dosing would maintain exposures within the range of clinical experience, the
      individual AUC distributions with fixed dosing were compared with the range of
      exposures from the pembrolizumab doses that were evaluated in early studies (2
      mg/kg Q3W, 10 mg/kg Q3W/Q2W). RESULTS: Body-weight dependence of clearance was
      characterized by a power relationship with an exponent of 0.578, a value
      consistent with fixed- and weight-based dosing providing similar control of PK
      variability. A fixed dose of 200 mg Q3W was investigated in trials based on
      predicted exposures maintained within the established exposure range in all
      patients. Mean (% CV, n) AUCss, 6-weeks was 1.87 (37%, 830), 1.38 (38%, 760) and
      7.63 (35%, 1405) mg*day/mL in patients receiving 200 mg, 2 mg/kg and 10 mg/kg Q3W
      pembrolizumab. High-weight patients had the lowest exposures with 200 mg Q3W;
      however, exposures in this group (>90 kg) were within the range of prior clinical
      experience at 2 mg/kg Q3W associated with near maximal efficacy. CONCLUSIONS:
      Doses of 200 mg and 2 mg/kg provide similar exposure distributions with no
      advantage to either dosing approach with respect to controlling PK variability.
      These findings suggest that weight-based and fixed-dose regimens are appropriate
      for pembrolizumab.

PMID- 28515945
TI  - Exposure to occupational hazards for pregnancy and sick leave in pregnant
      workers: a cross-sectional study.
AB  - BACKGROUND: This study aimed to investigate the association between exposure to
      occupational hazards for pregnancy and sick leave (SL) in pregnant workers.
      METHODS: A cross-sectional study was performed in French occupational health
      services in 2014. Occupational hazards for pregnancy were assessed by
      occupational health physicians (OHPs). After delivery and at the time of
      returning to work, 1,495 eligible workers were interviewed by OHPs. Information
      on SL was self-reported. Risk ratios (RRs) were calculated from multivariable
      analyses based on a generalized linear model with a Bernoulli distribution and a
      log link adjusted for selected confounders for binary outcomes or zero-inflated
      negative binomial regression for count outcomes. RESULTS: Among recruited
      workers, 74.9% presented "at least one SL" during pregnancy. After adjustment,
      the cumulative index of occupational hazards (0, 1-2, 3-4, >= 5 risks) for
      pregnancy was significantly associated with "at least one SL" during pregnancy in
      a dose-response relationship. This gradient was also observed with "early SL"
      (<15 week gestation): from 1 to 2 risks, RR = 1.48 (95% confidence intervals
      (CIs): 0.92-2.38); from 3 to 4 risks, RR = 2.03 (95% CI: 1.25-3.30); equal to or
      higher than five risks, RR = 2.90 (95% CI: 1.89-4.44); with "duration of absence"
      (adjusted mean): from 1 to 2 risks, m = 38.6 days; from 3 to 4 risks, m = 46.8
      days; equal to or higher than five risks, m = 53.8 days. We also found that
      deprivation, pregnancy at risk, assisted reproductive therapy, work-family
      conflicts, home-work commuting felt as difficult and young age are associated
      with a higher risk of SL. CONCLUSIONS: Our results support the assertion that
      pregnant workers exposed to occupational hazards for pregnancy without medical
      complications are also at risk of taking SL during pregnancy. More prevention in
      the workplace for pregnant workers exposed to occupational hazards could reduce
      SL.

PMID- 28515942
TI  - A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen
      modulation in leukemia cell lines.
AB  - BACKGROUND: Clinical success with chimeric antigen receptor (CAR)- based
      immunotherapy for leukemia has been accompanied by the associated finding that
      antigen-escape variants of the disease are responsible for relapse. To target
      hematologic malignancies with a chimeric antigen receptor (CAR) that targets two
      antigens with a single vector, and thus potentially lessen the chance of leukemic
      escape mutations, a tandem-CAR approach was investigated. METHODS: Antigen
      binding domains from the FMC63 (anti-CD19) and Leu16 (anti-CD20) antibodies were
      linked in differing configurations to transmembrane and T cell signaling domains
      to create tandem-CARs. Expression on the surface of primary human T cells was
      induced by transduction with a single lentiviral vector (LV) encoding the tandem
      CAR. Tandem-CARs were compared to single antigen targeting CARs in vitro and in
      vivo, and to an admixture of transduced cells expressing each CAR in vivo in
      immunodeficient (NSG) disease-bearing mice. RESULTS: Tandem constructs efficient
      killed the Raji leukemia cell line both in vitro and in vivo. Tandem CARs
      generated less cytokine than the CD20 CAR, but similar to CD19 CARs, on their
      own. In co-culture experiments at low effector to target ratios with both single-
      and tandem- CAR-T cells, a rapid down-modulation of full-length CD19 expression
      was seen on leukemia targets. There also was a partial down-modulation of CD22,
      and to a lesser degree, of CD20. Our data also highlight the extreme sensitivity
      of the NALM-6 cell line to general lymphocyte-mediated cytotoxicity. While single
      and tandem constructs were effective in vivo in a standard setting, in a high
      disease burden setting, the tandem CAR proved both effective and less toxic than
      an admixture of transduced T cell populations expressing single CARs. CONCLUSION:
      Tandem CARs are equally effective in standard disease models to single antigen
      specificity CARs, and may be both more effective and less toxic in a higher
      disease burden setting. This may be due to optimized cell killing with more
      moderate cytokine production. The rapid co-modulation of CD19, CD20, and CD22 may
      account for the ability to rapidly evolve escape mutants by selecting for
      leukemic clones that not require these target antigens for continued expansion.

PMID- 28515944
TI  - Identifying baseline immune-related biomarkers to predict clinical outcome of
      immunotherapy.
AB  - As cancer strikes, individuals vary not only in terms of factors that contribute
      to its occurrence and development, but as importantly, in their capacity to
      respond to treatment. While exciting new therapeutic options that mobilize the
      immune system against cancer have led to breakthroughs for a variety of
      malignancies, success is limited to a subset of patients. Pre-existing
      immunological features of both the host and the tumor may contribute to how
      patients will eventually fare with immunotherapy. A broad understanding of
      baseline immunity, both in the periphery and in the tumor microenvironment, is
      needed in order to fully realize the potential of cancer immunotherapy. Such
      interrogation of the tumor, blood, and host immune parameters prior to treatment
      is expected to identify biomarkers predictive of clinical outcome as well as to
      elucidate why some patients fail to respond to immunotherapy. To approach these
      opportunities for progress, the Society for Immunotherapy of Cancer (SITC)
      reconvened the Immune Biomarkers Task Force. Comprised of an international
      multidisciplinary panel of experts, Working Group 4 sought to make
      recommendations that focus on the complexity of the tumor microenvironment, with
      its diversity of immune genes, proteins, cells, and pathways naturally present at
      baseline and in circulation, and novel tools to aid in such broad analyses.

PMID- 28515672
TI  - Measurement of prompt and nonprompt [Formula: see text] production in [Formula:
      see text] and [Formula: see text] collisions at [Formula: see text].
AB  - This paper reports the measurement of [Formula: see text] meson production in
      proton-proton ([Formula: see text]) and proton-lead ([Formula: see text])
      collisions at a center-of-mass energy per nucleon pair of [Formula: see text] by
      the CMS experiment at the LHC. The data samples used in the analysis correspond
      to integrated luminosities of 28[Formula: see text] and 35[Formula: see text] for
      [Formula: see text] and [Formula: see text] collisions, respectively. Prompt and
      nonprompt [Formula: see text] mesons, the latter produced in the decay of
      [Formula: see text] hadrons, are measured in their dimuon decay channels.
      Differential cross sections are measured in the transverse momentum range of
      [Formula: see text], and center-of-mass rapidity ranges of [Formula: see text]
      ([Formula: see text]) and [Formula: see text] ([Formula: see text]). The nuclear
      modification factor, [Formula: see text], is measured as a function of both
      [Formula: see text] and [Formula: see text]. Small modifications to the [Formula:
      see text] cross sections are observed in [Formula: see text] relative to
      [Formula: see text] collisions. The ratio of [Formula: see text] production cross
      sections in [Formula: see text]-going and Pb-going directions, [Formula: see
      text], studied as functions of [Formula: see text] and [Formula: see text], shows
      a significant decrease for increasing transverse energy deposited at large
      pseudorapidities. These results, which cover a wide kinematic range, provide new
      insight on the role of cold nuclear matter effects on prompt and nonprompt
      [Formula: see text] production.

PMID- 28515946
TI  - The responses of subjective feeling, task performance ability, cortisol and HRV
      for the various types of floor impact sound: a pilot study.
AB  - BACKGROUND: Recently, noise coming from the neighborhood via floor wall has
      become a great social problem. The noise between the floors can be a cause of
      physical and psychological problems, and the different types of floor impact
      sound (FIS) may have the different effects on the human's body and mind. The
      purpose of this study is to assess the responses of subjective feeling, task
      performance ability, cortisol and HRV for the various types of floor impact.
      METHODS: Ten men and 5 women were enrolled in our study, and the English
      listening test was performed under the twelve different types of FIS, which were
      made by the combinations of bang machine (B), tapping machine (T), impact ball
      (I) and sound-proof mattress (M). The 15 subjects were exposed to each FIS for
      about 3 min, and the subjective annoyance, performance ability (English listening
      test), cortisol level of urine/saliva and heart rate variability (HRV) were
      examined. The sound pressure level (SPL) and frequency of FIS were analyzed.
      Repeated-measures ANOVA, paired t-test, Wilcoxon signed rank test were performed
      for data analysis. RESULTS: The SPL of tapping machine (T) was reduced with the
      soundproof mattress (M) by 3.9-7.3 dBA. Impact ball (I) was higher than other FIS
      in low frequency (31.5-125 Hz) by 10 dBA, and tapping machine (T) was higher than
      other FIS in high frequency (2-4 k Hz) by 10 dBA. The subjective annoyance is
      highest in the combination of bang machine and tapping machine (BT), and next in
      the tapping machine (T). The English listening score was also lowest in the BT,
      and next in T. The difference of salivary cortisol levels between various types
      of FIS was significant (p = 0.003). The change of HRV parameters by the change of
      FIS types was significant in some parameters, which were total power (TP) (p =
      0.004), low frequency (LF) (p = 0.002) and high frequency (HF) (p = 0.011).
      CONCLUSIONS: These results suggest that the human's subjective and objective
      responses were different according to FIS types and those combinations.

PMID- 28515952
TI  - Potential role of high-stress employment in hypertension.
AB  - We report a patient with a reduction in blood pressure through cessation of high
      stress employment.

PMID- 28515950
TI  - Factors associated with poor self-reported health within the UK military and
      comparisons with the general population: a cohort study.
AB  - OBJECTIVE: To investigate the self-rated health of the UK military and explore
      factors associated with poor self-rated health. Compare self-rated health of the
      military to the general population. DESIGN: A cohort study. PARTICIPANTS: A total
      of 7626 serving and ex-serving UK military personnel, aged between 25 and 49;
      19,452,300 civilians from England and Wales. SETTING: United Kingdom (military),
      England and Wales (civilians). MAIN OUTCOME MEASURES: Self rated health for both
      populations. Additional data for the military sample included measures of
      symptoms of common mental disorder (General Health Questionnaire-12), probable
      post-traumatic stress disorder (post-traumatic stress disorder checklist Civilian
      Version), alcohol use (Alcohol Use Disorders Identification Test), smoking
      behaviour, history of self-harm and body mass index. RESULTS: In the military
      sample, poor self-rated health was significantly associated with: common mental
      disorders and post-traumatic stress disorder symptomology, a history of self
      harm, being obese, older age (ages 35-49) and current smoking status. However,
      the majority of military personnel report good health, with levels of poor self
      rated health (13%) not significantly different to those reported by the general
      population (12.1%). CONCLUSIONS: Self-rated health appears to relate to aspects
      of both physical and psychological health. The link between poor self-rated
      health and psychological ill-health emphasises the need for military support
      services to continue addressing mental health problems.

PMID- 28515948
TI  - Cerebral air embolism associated with penetrating lung injury: a case report and
      review of the literature.
AB  - CASE: A 44-year-old man intentionally stabbed himself in the anterior neck and
      left thorax with a fruit knife. Physical examination revealed two open wounds
      entering the thoracic cavity in the front chest, and a stab wound entering the
      trachea at the neck. Two chest tubes were initially inserted for the left lung
      injury with open hemopneumothorax. Nevertheless, the worsening oxygenation
      required positive pressure ventilation (PPV) with endotracheal intubation.
      OUTCOME: Right hemiparesis was found during weaning from PPV. Magnetic resonance
      imaging revealed multiple infarctions in the area of the bifrontal and right
      temporal lobes. Cerebral air embolism (CAE) was strongly suspected from the
      imaging findings and clinical course. CONCLUSION: We concluded that mechanical
      ventilation was strongly involved in the occurrence of CAE. If delayed abnormal
      neurological findings are observed in patients with penetrating lung injuries
      receiving PPV management, CAE should be considered.

PMID- 28515953
TI  - An autopsy of intravascular large B-cell lymphoma with hemophagocytic syndrome.
AB  - Intravascular large B-cell lymphoma presents with highly variable symptoms caused
      by the occlusion of small vessels by neoplastic cells in a variety of organs.

PMID- 28515947
TI  - The impact of body armor on physical performance of law enforcement personnel: a
      systematic review.
AB  - BACKGROUND: The law enforcement officer profession requires performance of
      arduous occupational tasks while carrying an external load, consisting of, at
      minimum, a chest rig, a communication system, weaponry, handcuffs, personal
      protective equipment and a torch. The aim of this systematic review of the
      literature was to identify and critically appraise the methodological quality of
      published studies that have investigated the impacts of body armour on task
      performance and to synthesize and report key findings from these studies to
      inform law enforcement organizations. METHODS: Several literature databases
      (Medline, CINAHL, SPORTDiscus, EMBAS) were searched using key search words and
      terms to identify appropriate studies. Studies meeting the inclusion criteria
      were critically evaluated using the Downs and Black protocol with inter-rater
      agreement determined by Cohen's Kappa. RESULTS: Sixteen articles were retained
      for evaluation with a mean Downs and Black score of 73.2 +/- 6.8% (k = 0.841).
      Based on the research quality and findings across the included studies, this
      review determined that while effects of body armour on marksmanship and
      physiological responses have not yet been adequately ascertained, body armour
      does have significant physical performance and biomechanical impacts on the
      wearer, including: a) increased ratings of perceived exertion and increased time
      to complete functional tasks, b) decreased work capability (indicated by
      deterioration in fitness test scores), c) decreased balance and stability, and d)
      increased ground reaction forces. CONCLUSIONS: Given the physical performance and
      biomechanical impacts on the wearer, body armour should be carefully selected,
      with consideration of the physical fitness of the wearers and the degree to which
      the armour systems can be ergonomically optimized for the specific population in
      question.

PMID- 28515954
TI  - A prospective cohort study of thoracic ultrasound in acute respiratory failure:
      the C3PO protocol.
AB  - OBJECTIVES: This study was performed to assess the clinical utility of a
      standardised thoracic ultrasound examination when added to standard care in
      patients with acute respiratory failure admitted to an intermediate care unit.
      This study aimed to assess the impact on clinical diagnosis, clinician confidence
      and management. Ultrasound has been shown to have utility in patients admitted to
      intensive care and emergency; however, utility in a ward setting is unknown.
      DESIGN: Prospective cohort study. SETTING: Tertiary hospital in Melbourne,
      Australia. PARTICIPANTS: 50 patients with acute respiratory failure requiring
      admission to an intermediate care unit. MAIN OUTCOME MEASURES: (1) Change in
      clinical diagnosis or additional clinical diagnosis following thoracic
      ultrasound. (2) Change in diagnostic confidence following thoracic ultrasound.
      (3) Change to management following thoracic ultrasound. RESULTS: In 34% of
      patients, ultrasound detected unexpected findings that changed or added to the
      clinical diagnosis. Diagnostic confidence was increased in 44%, and the treating
      clinician altered the management plan in 30% as a result of the ultrasound.
      Ultrasound was particularly useful in clarifying the diagnosis in patients with
      multiple initial diagnoses, reducing to a single diagnosis in 69%. CONCLUSIONS:
      Thoracic ultrasound has clinical utility in non-intubated adults with acute
      respiratory failure managed outside intensive care settings. It changed
      aetiological diagnosis, increases diagnostic confidence and altered clinical
      management in one out of three patients scanned. Our results suggest extended
      utility of thoracic ultrasound in acute respiratory failure to a broader context
      outside the intensive care unit population.

PMID- 28515955
TI  - Effects of resistant dextrin for weight loss in overweight adults: a systematic
      review with a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Randomized controlled trials (RCTs) reported that resistant dextrin
      (RD) exerted pleiotropic effects on humans. However, limited information is
      available on the effects of RD for weight loss. We conducted a systematic review
      with a meta-analysis to summarize the available literature and compare the
      efficacy of RD for weight loss with that of a placebo in overweight adults.
      METHODS: We searched the electronic databases MEDLINE, EMBASE, The Cochrane
      Central Register of Controlled Trials (CENTRAL), CINAHL, Web of Science,
      ClincalTrials.gov, and Japana Centra Revuo Medicina (Ichushi-web) for studies
      from their onset to November 2016, and there was no language restriction. Trials
      were included if they were RCTs (1) comparing the effects of RD with a placebo in
      adults (18 years or older), (2) reporting body mass index, and (3) including
      overweight/obese subjects as defined by the authors of RCTs. The weighted mean
      difference with a 95% confidence interval (CI) was calculated using a random
      effects model. RESULTS: Of the 484 studies retrieved, 3 RCTs involving 275
      subjects were included in our review. The durations of RCTs ranged between 8 and
      12 weeks. All RCTs were conducted in Asian countries. RD significantly improved
      body mass index [mean difference -0.39 (95% CI -0.57 to -0.21) kg/m2, p < 0.01]
      and body weight [mean difference -0.81 (95% CI -0.93 to -0.69) kg, p < 0.01] in
      overweight adults. CONCLUSION: Our review suggests that RD exerts beneficial
      effects for weight loss in overweight adults. More RCTs with different
      populations and longer follow-ups are needed in order to confirm that
      supplementation with RD has beneficial effects for weight loss in overweight
      adults. We consider this review to provide important information for the future
      submission of food with health claims.

PMID- 28515951
TI  - Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and
      zinc gluconate, and the role of zinc dosage.
AB  - OBJECTIVE: To compare the efficacy of zinc acetate lozenges with zinc gluconate
      lozenges in common cold treatment and to examine the dose-dependency of the
      effect. DESIGN: Meta-analysis. SETTING: Placebo-controlled zinc lozenge trials,
      in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on
      common cold duration was calculated by using inverse-variance random-effects
      method. PARTICIPANTS: Seven randomised trials with 575 participants with
      naturally acquired common colds. MAIN OUTCOME MEASURE: Duration of the common
      cold. RESULTS: The mean common cold duration was 33% (95% CI 21% to 45%) shorter
      for the zinc groups of the seven included trials. Three trials that used lozenges
      composed of zinc acetate found that colds were shortened by 40% and four trials
      that used zinc gluconate by 28%. The difference between the two salts was not
      significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc
      doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials
      used zinc doses of 192-207 mg/day and found an effect of 35%. The difference
      between the high-dose and low-dose zinc trials was not significant: 2 percentage
      points (95% CI: -29 to + 32). CONCLUSIONS: Properly composed zinc gluconate
      lozenges may be as effective as zinc acetate lozenges. There is no evidence that
      zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the
      common cold. Common cold patients may be encouraged to try zinc lozenges for
      treating their colds. The optimal lozenge composition and dosage scheme need to
      be investigated further.

PMID- 28515949
TI  - Cerebellum: An explanation for dystonia?
AB  - Dystonia is a movement disorder that is characterized by involuntary muscle
      contractions, abnormal movements and postures, as well as by non-motor symptoms,
      and is due to abnormalities in different brain areas. In this article, we focus
      on the growing number of experimental studies aimed at explaining the
      pathophysiological role of the cerebellum in dystonia. Lastly, we highlight gaps
      in current knowledge and issues that future research studies should focus on as
      well as some of the potential applications of this research avenue. Clarifying
      the pathophysiological role of cerebellum in dystonia is an important concern
      given the increasing availability of invasive and non-invasive stimulation
      techniques and their potential therapeutic role in this condition.

PMID- 28515958
TI  - Attitudes and preferences for the clinical management of hypertension and
      hypertension-related cerebrovascular disease in the general practice: results of
      the Italian hypertension and brain survey.
AB  - BACKGROUND: The aim of this survey was to evaluate attitudes and preferences for
      the clinical management of hypertension and hypertension-related cerebrovascular
      diseases (CVD) in Italy. METHODS: A predefined 16-item survey questionnaire was
      anonymously administered to a large community sample of general practitioners
      (GPs), trained by specialized physicians (SPs), who have been included in an
      educational program between January and November 2015. RESULTS: A total of 591
      physicians, among whom 48 (8%) training SPs and 543 (92%) trained GPs, provided
      12,258 valid answers to the survey questionnaire. Left ventricular hypertrophy
      was considered the most frequent marker of hypertension-related organ damage,
      whereas atrial fibrillation and carotid atherosclerosis were considered
      relatively not frequent (10-20%). The most appropriate blood pressure (BP)
      targets to be achieved in hypertensive patients with CVD were <140/90 mmHg for
      SPs and <135/85 mmHg for GPs. To achieve these goals, ACE inhibitors were
      considered the most effective strategies by GPs, whereas SPs expressed a
      preference for ARBs, both in monotherapies and in combination therapies with beta
      blockers. CONCLUSIONS: This survey demonstrates that Italian physicians
      considered left ventricular hypertrophy frequently associated to CVD and that
      drugs inhibiting the renin-angiotensin system the most appropriate therapy to
      manage hypertension and hypertension-related CVD.

PMID- 28515956
TI  - Effects of phosalone consumption via feeding with or without sodium bentonite on
      performance, blood metabolites and its transition to milk of Iranian Baluchi
      sheep.
AB  - BACKGROUND: Transfer of pesticides from environment to animal products is
      inevitable, so the purpose of the present work was to evaluate phosalone
      consumption via feeding with or without sodium bentonite (SB) on performance,
      blood metabolites and its transition to milk of Iranian Baluchi sheep. METHODS:
      Twenty Baluchi ewes were divided into four treatments (P1 as control, P2, P3, and
      P4) of five animals in which phosalone, an organophosphate pesticide, was given
      via diet (only for P2 and P3) at a dose of 280 mg/sheep/day for 63 consecutive
      days. The SB (32 g/sheep/day; for P3 and P4) was also evaluated for its ability
      to reduce deleterious effects of phosalone in the sheep diets. The control group
      (P1) did not receive any phosalone and SB during the experiment. Sampling was
      conducted in two periods of time including weeks 5 and 9. RESULTS: Phosalone
      residues were observed in the milk samples of P2 and P3 groups during two
      sampling periods. During period 1, the transfer rate of phosalone from feed to
      milk was 0.23 and 0.02%, respectively for the contaminated diets (P2 and P3),
      which is relatively similar to period 2 (0.22 and 0.02%). Only 0.34 (period 1)
      and 0.36% (period 2) of phosalone residue are excreted in the feces of P2 group
      following its daily consumption. Transfer of phosalone from feed to milk was
      affected (P < 0.05) by the dietary inclusion of a commercial SB, as it (SB)
      decreased excretion of phosalone via milk (P3). The phosalone and SB alone or
      together had no significant effect (P > 0.05) on the dry matter intake (DMI) and
      body weight (BW) gain, but feed efficiency, milk production, milk fat, dry matter
      (DM) and organic matter (OM) digestibility, acetylcholinesterase (AChE)
      inhibitory activity, hemoglobin (Hb), red blood cell (RBC), serum glutamic
      pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT),
      albumin and mean corpuscular hemoglobin concentration (MCHC) affected by the
      treatments in period 1 or 2 (P < 0.05). The Hb, RBC, and MCHC were significantly
      decreased (P < 0.05) by about 9.72, 20.77, and 9.71%, respectively in the group
      P2 as compared to those of the control group during period 1. The AChE inhibitory
      activity (period 1 and 2) significantly increased when phosalone administered via
      the diet (P < 0.05). CONCLUSIONS: Although there were no adverse effects on the
      performance of sheep following the intake of phosalone alone (P2 vs. P1), but
      other research on the long and short times to the phosalone in high and low doses
      with more animals is suggested. Overall, compared to the control group, addition
      of SB in the diet of sheep improved nutrient digestibility, animal performance,
      and milk health.

PMID- 28515957
TI  - A psychologically informed, audiologist-delivered, manualised intervention for
      tinnitus: protocol for a randomised controlled feasibility trial (Tin Man study).
AB  - BACKGROUND: Chronic tinnitus is a common incurable condition often associated
      with depression, anxiety, insomnia and reduced quality of life. Within National
      Health Service (NHS) audiology in the United Kingdom (UK), no standard protocol
      currently exists for the treatment of tinnitus. Counselling is only available in
      less than half of audiology departments, and there is no agreed standard for what
      constitutes tinnitus counselling. There is substantial evidence from systematic
      reviews for the clinical benefit of cognitive behaviour therapy (CBT) for
      tinnitus delivered by clinical psychologists or psychiatrists, but no studies
      have sufficiently evidenced the NHS model of tinnitus care where management is
      increasingly being delivered by audiology professionals. In a pilot randomised
      controlled trial (RCT), this study aims to evaluate the feasibility of comparing
      a psychologically informed guidance manual developed to support audiologist
      management of tinnitus with usual treatment. METHODS/DESIGN: Phase 1 consisted of
      three development stages: (1) a scoping review to generate a comprehensive set of
      tinnitus counselling components, (2) a Delphi survey involving expert patients (n
      = 18) and clinicians (n = 21) to establish consensus on the essential core
      attributes of tinnitus counselling, and (3) incorporation of these elements into
      a manualised care protocol. In phase 2, following training in a dedicated
      workshop, the manualised intervention will be delivered by three experienced
      audiologists across three different sites. Patients (n = 30) will be randomly
      allocated to receive either (1) psychologically informed management from an
      audiologist trained to deliver the manualised intervention or (2) treatment as
      usual (TAU) from an audiologist who has not received this training. Quantitative
      outcome measures will be administered at baseline, discharge and 6-month follow
      up. Qualitative interviews with participating patients and clinicians will be
      conducted to gather perspectives on the feasibility and acceptability of the
      manualised intervention. DISCUSSION: The feasibility of proceeding to a
      definitive RCT will be assessed via compliance with the manual, willingness to be
      randomised, number of eligible participants, rate of recruitment, retention and
      collection of quantitative outcome measures. This research offers an important
      first step to an evidence-based, standardised and accessible approach to tinnitus
      care. TRIAL REGISTRATION: ISRCTN13059163. Date of registration: 6 May 2016.

PMID- 28515962
TI  - Analyses of publicly available genomics resources define FGF-2-expressing bladder
      carcinomas as EMT-prone, proliferative tumors with low mutation rates and high
      expression of CTLA-4, PD-1 and PD-L1.
AB  - FGF-2 is overexpressed in a subset of invasive bladder carcinomas and its
      overexpression correlates with poor prognosis. Analyses of publicly available
      databases addressing the molecular mechanisms that may be responsible for the
      poor prognosis of these tumors, revealed that FGF-2 expression correlates
      positively with the expression of EMT-promoting transcription factors and with
      changes in gene expression that are characteristic of EMT. The same analyses also
      revealed that FGF-2 correlates negatively with the expression, mutation and copy
      number variations of FGFR-3, all of which are associated with non-invasive
      bladder carcinomas. Finally, they showed that FGF-2 expression correlates with
      the expression of FGFR-1, the expression of the IIIc variant of FGFR-2 and with
      the expression of Akt3. The latter observation is significant because our earlier
      studies had shown that Akt3 regulates FGFR-2 alternative splicing, shifting the
      balance toward the IIIc relative to the IIIb FGFR-2 splice variant. Since the
      IIIc variant is recognized by FGF-2, while the IIIb variant is not, we conclude
      that Akt3 may facilitate the FGF-2 response. FGF-2 is known to promote the
      expression of KDM2B, which functions in concert with EZH2 to repress the EZH2
      targeting microRNA miR-101, activating a switch, which stably upregulates EZH2.
      TCGA data showing a correlation between KDM2B and EZH2 expression and Oncomine
      data, showing a correlation between KDM2B and tumor progression, strongly support
      the role of the FGF-2/KDM2B/miR-101/EZH2 pathway in bladder cancer. These
      observations combined, suggest a model according to which FGF-2 induces EMT, cell
      proliferation and cancer stem cell self-renewal by coupling the Akt3 and KDM2B
      controlled pathways outlined above, in bladder carcinomas. Further analyses of
      publicly-available databases, revealed that FGF-2-expressing bladder carcinomas
      carry fewer genetic alterations and they tend to express high levels of CTLA-4,
      PD-1 and PD-L1, which suggests immune blockade by checkpoint activation. EMT,
      enhanced proliferation and immune checkpoint activation combined, may be
      responsible for the poor prognosis of FGF-2-expressing bladder carcinomas.

PMID- 28515959
TI  - Impact of image quality on OCT angiography based quantitative measurements.
AB  - BACKGROUND: To study the impact of image quality on quantitative measurements and
      the frequency of segmentation error with optical coherence tomography angiography
      (OCTA). METHODS: Seventeen eyes of 10 healthy individuals were included in this
      study. OCTA was performed using a swept-source device (Triton, Topcon). Each
      subject underwent three scanning sessions 1-2 min apart; the first two scans were
      obtained under standard conditions and for the third session, the image quality
      index was reduced using application of a topical ointment. En face OCTA images of
      the retinal vasculature were generated using the default segmentation for the
      superficial and deep retinal layer (SRL, DRL). Intraclass correlation coefficient
      (ICC) was used as a measure for repeatability. The frequency of segmentation
      error, motion artifact, banding artifact and projection artifact was also
      compared among the three sessions. RESULTS: The frequency of segmentation error,
      and motion artifact was statistically similar between high and low image quality
      sessions (P = 0.707, and P = 1 respectively). However, the frequency of
      projection and banding artifact was higher with a lower image quality. The vessel
      density in the SRL was highly repeatable in the high image quality sessions (ICC
      = 0.8), however, the repeatability was low, comparing the high and low image
      quality measurements (ICC = 0.3). In the DRL, the repeatability of the vessel
      density measurements was fair in the high quality sessions (ICC = 0.6 and ICC =
      0.5, with and without automatic artifact removal, respectively) and poor
      comparing high and low image quality sessions (ICC = 0.3 and ICC = 0.06, with and
      without automatic artifact removal, respectively). CONCLUSIONS: The frequency of
      artifacts is higher and the repeatability of the measurements is lower with lower
      image quality. The impact of image quality index should be always considered in
      OCTA based quantitative measurements.

PMID- 28515963
TI  - Eliminating Racial/Ethnic Disparities in AIDS Clinical Trials in the United
      States: A Qualitative Exploration of an Efficacious Social/Behavioral
      Intervention.
AB  - BACKGROUND: African American/Black and Hispanic persons living with HIV (AABH
      PLWH) are under-represented in AIDS clinical trials (ACTs) in the United States.
      Barriers AABH-PLWH experience to ACTs are multi-faceted, including distrust of
      medical research, low levels of knowledge, unsupportive social norms, lack of
      referral, and challenges navigating ACT systems. In past research we found a
      multi-component peer-driven intervention was efficacious in boosting rates of
      screening for/enrollment into ACTs. The present qualitative study seeks to
      understand AABH-PLWH's perspectives on which specific intervention features or
      components had utility. Interventions features explored included structural
      elements (e.g., small group sessions, individual sessions on the ACT research
      unit); approaches (e.g., Motivational Interviewing); and specific components
      (e.g., small-group discussion of historical and cultural factors reducing
      participation among AABH-PLWH). METHODS: A total of 37 AABH-PLWH (mean age 50.6
      years, SD=7.5 years; 48.6% female; 62.2% African American/Black, 27.0% Hispanic)
      were purposively selected from a larger study for in-depth interviews, which were
      audio-recorded, transcribed verbatim, and analyzed using systematic content
      analysis. RESULTS: We found the intervention improved knowledge and positive
      attitudes toward ACTs, and triggered social-level facilitators such as altruism
      and more positive social norms. Discussions of cultural/historical barriers to
      ACTs associated with race/ethnicity had utility. Holding a session on the ACT
      research unit reduced fear and increased motivation. Results highlighted the
      value of Motivational Interviewing, and several components were perceived as less
      useful (e.g., involving social network members in ACT decisions). CONCLUSION:
      Findings can inform future intervention designs to address racial/ethnic
      disparities in ACTs and have implications for trials of other conditions where
      racial/ethnic disparities persist.

PMID- 28515960
TI  - Patient-Centered Network of Learning Health Systems: Developing a resource for
      clinical translational research.
AB  - INTRODUCTION: The Learning Health System Network clinical data research network
      includes academic medical centers, health-care systems, public health
      departments, and health plans, and is designed to facilitate outcomes research,
      pragmatic trials, comparative effectiveness research, and evaluation of
      population health interventions. METHODS: The Learning Health System Network is 1
      of 13 clinical data research networks assembled to create, in partnership with 20
      patient-powered research networks, a National Patient-Centered Clinical Research
      Network. RESULTS AND CONCLUSIONS: Herein, we describe the Learning Health System
      Network as an emerging resource for translational research, providing details on
      the governance and organizational structure of the network, the key milestones of
      the current funding period, and challenges and opportunities for collaborative
      science leveraging the network.

PMID- 28515961
TI  - Has Adolescent Childbearing Been Eclipsed by Nonmarital Childbearing?
AB  - Adolescent childbearing has received decreasing attention from academics and
      policymakers in recent years, which may in part reflect the decline in its
      incidence. Another reason may be its uncoupling from nonmarital childbearing.
      Adolescent childbearing became problematized only when it began occurring
      predominantly outside marriage. In recent decades, there have been historic rises
      in the rate of nonmarital childbearing, and importantly, the rise has been
      steeper among older mothers than among adolescent mothers. Today, two out of five
      births are to unmarried women, and the majority of these are to adults, not
      adolescents. Nonmarital childbearing is in and of itself associated with lower
      income and poorer maternal and child outcomes. However, unmarried adolescent
      mothers might face more difficulties than unmarried adult mothers due to their
      developmental status, education, living arrangements, and long-term prospects for
      work. If this is true, then the focus on adolescent mothers ought to continue. We
      suggest several facets of adolescent motherhood deserving of further study, and
      recommend that future research use unmarried mothers in their early 20s as a
      realistic comparison group.

PMID- 28515966
TI  - Predicting students' happiness from physiology, phone, mobility, and behavioral
      data.
AB  - In order to model students' happiness, we apply machine learning methods to data
      collected from undergrad students monitored over the course of one month each.
      The data collected include physiological signals, location, smartphone logs, and
      survey responses to behavioral questions. Each day, participants reported their
      wellbeing on measures including stress, health, and happiness. Because of the
      relationship between happiness and depression, modeling happiness may help us to
      detect individuals who are at risk of depression and guide interventions to help
      them. We are also interested in how behavioral factors (such as sleep and social
      activity) affect happiness positively and negatively. A variety of machine
      learning and feature selection techniques are compared, including Gaussian
      Mixture Models and ensemble classification. We achieve 70% classification
      accuracy of self-reported happiness on held-out test data.

PMID- 28515965
TI  - Anatomic Variations of the Right Portal Vein: Prevalence, Imaging Features, and
      Implications for Successful Transjugular Intrahepatic Portosystemic Shunt
      Creation.
AB  - Given the widespread use of transjugular intrahepatic portosystemic shunt (TIPS)
      creation for the treatment of portal hypertensive complications, a working
      knowledge of portal venous anatomy is critical for interventional radiologists.
      The right portal vein - which is most commonly accessed during TIPS - is subject
      to various anatomic variants that may potentially impact procedure success. This
      pictorial essay characterizes the anatomic patterns of the right portal vein
      branching in terms of type and frequency based on case series review. The work
      also explains the potential procedural implications of the right portal vein
      anatomic variations as they pertain to TIPS technical success.

PMID- 28515964
TI  - Radiologic-Pathologic Correlation: Acellular Dermal Matrix (Alloderm(r)) Used in
      Breast Reconstructive Surgery.
AB  - Acellular dermal matrix (ADM) such as Alloderm(r) is sometimes used in tissue
      reconstruction in primary and reconstructive breast surgeries. As ADM is
      incorporated into the native tissues, the evolving imaging findings that would
      correlate with varying degrees of host migration and neoangiogenesis into the
      matrix can be challenging to recognize. In the setting of a palpable or clinical
      area of concern after breast reconstructive surgery following breast cancer,
      confident diagnosis of a mass representing ADM rather than recurring or
      developing disease can be challenging. Such diagnostic imaging uncertainties
      generally result in short-term imaging and clinical follow-up, but occasionally,
      biopsy is performed for histopathological confirmation of benignity. A case of
      biopsy-proven Alloderm(r) is described. To the best of our knowledge, this is the
      first radiologic-pathologic correlation of ADM in the literature.

PMID- 28515967
TI  - Unintended Pregnancies in Brazil - A Challenge for the Recommendation to Delay
      Pregnancy Due to Zika.
AB  - Because of the potential link between the ongoing Zika virus outbreak and a surge
      in the number of cases of congenital microcephaly, officials in Latin America
      have recommended that women postpone pregnancy until this association is firmly
      established or the outbreak subsides. However, in all these countries a large
      proportion of babies are still born out of unplanned pregnancies. Teenage girls
      are particularly at high risk, as they often lack access to preventive
      contraception methods, or the knowledge to use them appropriately. To gauge the
      magnitude of the barriers preventing the implementation of such a recommendation
      in Brazil, the country so far most affected by the Zika epidemic, we evaluated
      pregnancy rates in teenage girls, and their spatial heterogeneity in the country,
      in recent years (2012-2014). Nearly 20% of children born in Brazil today
      (~560,000 live births) are by teenage mothers. Birth incidence is far higher in
      the tropical and poorer northern states. However, in absolute terms most births
      occur in the populous southeastern states, matching to a large extent the
      geographic distribution of dengue (an indicator of suitable climatic and
      sociodemographic conditions for the circulation of Aedes mosquitoes). These
      findings indicate that recommendation to delay pregnancy will leave over half a
      million pregnant adolescents in Brazil vulnerable to infection every year if not
      accompanied by effective education and real access to prevention.

PMID- 28515969
TI  - Application of Selective Bronchial Intubation versus Neurally Adjusted
      Ventilatory Assist in the Management of Unilateral Pulmonary Interstitial
      Emphysema: An Illustrative Case and the Literature Review.
AB  - In the treatment of left-sided pulmonary interstitial emphysema (PIE) in a 23
      week neonate, we used two ventilatory strategies: selective bronchial intubation
      from day 10 to 15 and neurally adjusted ventilatory assist (NAVA) from day 18 to
      26. We compared the effects and adverse effects of these two strategies. On
      selective bronchial intubation, desaturation was frequent. Fentanyl infusion was
      required. There was an episode of carbon dioxide retention coupled with
      hypotension. On NAVA, the neonate was clinically stable without the requirement
      of sedation. On selective bronchial intubation, ventilator setting in terms of
      mean airway pressure and oxygen requirement was higher, which came down on the
      first day of NAVA. Radiologically unilateral PIE did not resolve and became
      localized in the left middle zone of lung field on selective bronchial
      intubation. Also, the lobar collapse of ipsilateral, as well as contralateral
      lungs occurred. On NAVA, unilateral PIE resolved. NAVA might be a good option for
      the management of unilateral PIE.

PMID- 28515968
TI  - How Really Ancient Is Paulinella Chromatophora?
AB  - The ancestor of Paulinella chromatophora established a symbiotic relationship
      with cyanobacteria related to the Prochloroccocus/Synechococcus clade. This event
      has been described as a second primary endosymbiosis leading to a plastid in the
      making. Based on the rate of pseudogene disintegration in the endosymbiotic
      bacteria Buchnera aphidicola, it was suggested that the chromatophore in P.
      chromatophora has a minimum age of ~60 Myr. Here we revisit this estimation by
      using a lognormal relaxed molecular clock on the 18S rRNA of P. chromatophora.
      Our time estimates show that depending on the assumptions made to calibrate the
      molecular clock, P. chromatophora diverged from heterotrophic Paulinella spp. ~
      90 to 140 Myr ago, thus establishing a maximum date for the origin of the
      chromatophore.

PMID- 28515970
TI  - TWO-DIMENSIONAL VIDEO ANALYSIS IS COMPARABLE TO 3D MOTION CAPTURE IN LOWER
      EXTREMITY MOVEMENT ASSESSMENT.
AB  - BACKGROUND: Although 3D motion capture is considered the "gold standard" for
      recording and analyzing kinematics, 2D video analysis may be a more reasonable,
      inexpensive, and portable option for kinematic assessment during pre
      participation screenings. Few studies have compared quantitative measurements of
      lower extremity functional tasks between 2D and 3D. PURPOSE: To compare kinematic
      measurements of the trunk and lower extremity in the frontal and sagittal planes
      between 2D video camera and 3D motion capture analyses obtained concurrently
      during a SLS. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty-six
      healthy, recreationally active adults volunteered to participate. Participants
      performed three trials of the single leg squat on each limb, which were recorded
      simultaneously by three 2D video cameras and a 3D motion capture system.
      Dependent variables analyzed were joint displacement at the trunk, hip, knee, and
      ankle in the frontal and sagittal planes during the task compared to single leg
      quiet standing. RESULTS: Dependent variables exhibited moderate to strong
      correlations between the two measures in the sagittal plane (r = 0.51-.093), and
      a poor correlation at the knee in the frontal plane (r = 0.308) at (p <= 0.05)
      All other dependent variables revealed non-significant results between the two
      measures. Bland-Altman plots revealed strong agreement in the average mean
      difference in the amount of joint displacement between 2D and 3D in the sagittal
      plane (trunk = 1.68 o, hip = 2.60 o, knee = 0.74 o, and ankle = 3.12 o).
      Agreement in the frontal plane was good (trunk = 7.92  degrees , hip = -8.72 o,
      knee = -6.62 o, and ankle = 3.03  degrees ). CONCLUSION: Moderate to strong
      relationships were observed between 2D video camera and 3D motion capture
      analyses at all joints in the sagittal plane, and the average mean difference was
      comparable to the standard error of measure with goniometry. The results suggest
      that despite the lack of precision and ability to capture rotations, 2D
      measurements may provide a pragmatic method of evaluating sagittal plane joint
      displacement for assessing gross movement displacement and therein risk of lower
      extremity injury. LEVEL OF EVIDENCE: 3.

PMID- 28515971
TI  - PREDICTION OF FUNCTIONAL MOVEMENT SCREENTM PERFORMANCE FROM LOWER EXTREMITY RANGE
      OF MOTION AND CORE TESTS.
AB  - BACKGROUND: There are varied reports in the literature regarding the association
      of the Functional Movement ScreenTM (FMSTM) with injury. The FMSTM has been
      correlated with hamstring range of motion and plank hold times; however, limited
      research is available on the predictability of lower extremity range of motion
      (ROM) and core function on FMSTM performance. PURPOSE/HYPOTHESES: The purpose of
      this study was to examine whether active lower extremity ROM measurements and
      core functional tests predict FMSTM performance. The authors hypothesized that
      lower extremity ROM and core functional tests would predict FMSTM composite score
      (CS) and performance on individual FMSTM fundamental movement patterns. STUDY
      DESIGN: Descriptive cohort study. METHODS: Forty recreationally active
      participants had active lower extremity ROM measured, performed two core
      functional tests, the single leg wall sit hold (SLWS) and the repetitive single
      leg squat (RSLS), and performed the FMSTM. Independent t tests were used to
      assess differences between right and left limb ROM measures and outcomes of core
      functional tests. Linear and ordinal logistic regressions were used to determine
      the best predictors of FMSTM CS and fundamental movement patterns, respectively.
      RESULTS: On the left side, reduced DF and SLWS significantly predicted lower
      FMSTM CS. On the right side only reduced DF significantly predicted lower FMSTM
      CS. Ordinal logistic regression models for the fundamental movement patterns
      demonstrated that reduced DF ROM was significantly associated with lower
      performance on deep squat. Reduced left knee extension was significantly
      associated with better performance in left straight leg raise; while reduced
      right hip flexion was significantly associated with reduced right straight leg
      raise. Lower SLWS was associated with reduced trunk stability performance.
      CONCLUSIONS: FMSTM movement patterns were affected by lower extremity ROM and
      core function. Researchers should consider lower FMSTM performance as indicative
      of underlying issues in ROM and core function. Clinicians may consider ROM
      interventions and core training strategies to improve FMSTM CS. LEVEL OF
      EVIDENCE: Level 2B.

PMID- 28515972
TI  - DETERMINATION OF CLINICALLY RELEVANT DIFFERENCES IN FRONTAL PLANE HOP TESTS IN
      WOMEN'S COLLEGIATE BASKETBALL AND SOCCER PLAYERS.
AB  - BACKGROUND: ACL injury prevention programs are less successful in female
      basketball players than in soccer players. Previous authors have identified
      anthropometric and biomechanical differences between the athletes and different
      sport-specific demands, including a higher frequency of frontal plane activities
      in basketball. Current injury risk screening and preventive training practices do
      not place a strong emphasis on frontal plane activities. The medial and lateral
      triple hop for distance tests may be beneficial for use in the basketball
      population. HYPOTHESIS/PURPOSE: To 1) establish normative values for the medial
      and lateral triple hop tests in healthy female collegiate athletes, and 2)
      analyze differences in test scores between female basketball and soccer players.
      It was hypothesized that due to the frequent frontal plane demands of their
      sport, basketball players would exhibit greater performance during these frontal
      plane performance tests. STUDY DESIGN: Cross-sectional. METHODS: Thirty-two NCAA
      Division-1 female athletes (20 soccer, 12 basketball) performed three trials each
      of a medial and lateral triple hop for distance test. Distances were normalized
      to height and mass in order to account for anthropometric differences. Repeated
      measures ANOVAs were performed to identify statistically significant main effects
      of sport (basketball vs. soccer), and side (right vs. left), and sport x side
      interactions. RESULTS: After accounting for anthropometric differences, soccer
      players exhibited significantly better performance than basketball players in the
      medial and lateral triple hop tests (p < 0.05). Significant side differences (p =
      0.02) were identified in the entire population for the medial triple hop test,
      such that participants jumped farther on their left (400.3 +/- 41.5 cm) than
      right (387.9 +/- 43.4 cm) limbs, but no side differences were identified in the
      lateral triple hop. No significant side x sport interactions were identified.
      CONCLUSIONS: Women's basketball players exhibit decreased performance of frontal
      plane hop tests when compared to women's soccer players. Additionally, the medial
      triple hop for distance test may be effective at identifying side-to-side
      asymmetries. LEVEL OF EVIDENCE: 3.

PMID- 28515976
TI  - THE ACUTE EFFECTS OF CONCENTRIC VERSUS ECCENTRIC MUSCLE FATIGUE ON SHOULDER
      ACTIVE REPOSITIONING SENSE.
AB  - PURPOSE/BACKGROUND: Shoulder proprioception is essential in the activities of
      daily living as well as in sports. Acute muscle fatigue is believed to cause a
      deterioration of proprioception, increasing the risk of injury. The purpose of
      this study was to evaluate if fatigue of the shoulder external rotators during
      eccentric versus concentric activity affects shoulder joint proprioception as
      determined by active reproduction of position. STUDY DESIGN: Quasi-experimental
      trial. METHODS: Twenty-two healthy subjects with no recent history of shoulder
      pathology were randomly allocated to either a concentric or an eccentric exercise
      group for fatiguing the shoulder external rotators. Proprioception was assessed
      before and after the fatiguing protocol using an isokinetic dynamometer, by
      measuring active reproduction of position at 30  degrees  of shoulder external
      rotation, reported as absolute angular error. The fatiguing protocol consisted of
      sets of fifteen consecutive external rotator muscle contractions in either the
      concentric or eccentric action. The subjects were exercised until there was a 30%
      decline from the peak torque of the subjects' maximal voluntary contraction over
      three consecutive muscle contractions. RESULTS: A one-way analysis of variance
      test revealed no statistical difference in absolute angular error (p > 0.05)
      between concentric and eccentric groups. Moreover, no statistical difference (p >
      0.05) was found in absolute angular error between pre- and post-fatigue in either
      group. CONCLUSIONS: Eccentric exercise does not seem to acutely affect shoulder
      proprioception to a larger extent than concentric exercise. LEVEL OF EVIDENCE:
      2b.

PMID- 28515974
TI  - The Effect of Fatigue on Upper Quarter Y-Balance Test Scores in Recreational
      Weightlifters: A Randomized Controlled Trial.
AB  - BACKGROUND: A paucity of research currently exists for upper extremity return to
      sport testing. The Upper Quarter Y-Balance Test (YBT-UQ) is a clinical test of
      closed kinetic chain performance with demonstrated reliability. Prior
      investigations of the YBT-UQ were conducted with individuals in a resting state
      and no comparison to performance in a fatigued state has been conducted. PURPOSE:
      To examine the effect of upper extremity fatigue on the performance of the YBT-UQ
      in recreational weightlifters. STUDY DESIGN: Randomized controlled trial.
      METHODS: 24 participants who participated in recreational weight training three
      days per week were randomly allocated to a control or experimental group.
      Individuals in the control group were tested using the YBT-UQ and re-tested after
      a 20-minute rest period. Participants in the experimental group were tested with
      the YBT-UQ, performed an upper extremity exercise fatigue protocol, and
      immediately re-tested. Examiners were blinded to participant allocation. RESULTS:
      Differences from pre- to post-fatigue YBT-UQ testing revealed score reductions
      between 2.04cm - 12.16cm for both composite scores and individual reach
      directions. The repeated measures ANOVA revealed significant differences when
      comparing the pre- and post-testing results between the fatigue and non-fatigue
      groups for all individual directions (p <= .006) and composite scores both limbs
      (p<.035). CONCLUSION: The performance of an upper body fatigue protocol
      significantly reduces YBT-UQ scores in recreational weightlifters. LEVEL OF
      EVIDENCE: 1b.

PMID- 28515973
TI  - INTRA-RATER RELIABILITY OF THE MULTIPLE SINGLE-LEG HOP-STABILIZATION TEST AND
      RELATIONSHIPS WITH AGE, LEG DOMINANCE AND TRAINING.
AB  - BACKGROUND: Balance is a complex construct, affected by multiple components such
      as strength and co-ordination. However, whilst assessing an athlete's dynamic
      balance is an important part of clinical examination, there is no gold standard
      measure. The multiple single-leg hop-stabilization test is a functional test
      which may offer a method of evaluating the dynamic attributes of balance, but it
      needs to show adequate intra-tester reliability. PURPOSE: The purpose of this
      study was to assess the intra-rater reliability of a dynamic balance test, the
      multiple single-leg hop-stabilization test on the dominant and non-dominant legs.
      DESIGN: Intra-rater reliability study. METHODS: Fifteen active participants were
      tested twice with a 10-minute break between tests. The outcome measure was the
      multiple single-leg hop-stabilization test score, based on a clinically assessed
      numerical scoring system. Results were analysed using an Intraclass Correlations
      Coefficient (ICC2,1) and Bland-Altman plots. Regression analyses explored
      relationships between test scores, leg dominance, age and training (an alpha
      level of p = 0.05 was selected). RESULTS: ICCs for intra-rater reliability were
      0.85 for the dominant and non-dominant legs (confidence intervals = 0.62-0.95 and
      0.61-0.95 respectively). Bland-Altman plots showed scores within two standard
      deviations. A significant correlation was observed between the dominant and non
      dominant leg on balance scores (R2=0.49, p<0.05), and better balance was
      associated with younger participants in their non-dominant leg (R2=0.28, p<0.05)
      and their dominant leg (R2=0.39, p<0.05), and a higher number of hours spent
      training for the non-dominant leg R2=0.37, p<0.05). CONCLUSIONS: The multiple
      single-leg hop-stabilisation test demonstrated strong intra-tester reliability
      with active participants. Younger participants who trained more, have better
      balance scores. This test may be a useful measure for evaluating the dynamic
      attributes of balance. LEVEL OF EVIDENCE: 3.

PMID- 28515977
TI  - ESTABLISHING NORMATIVE CHANGE VALUES IN VISUAL ACUITY LOSS DURING THE DYNAMIC
      VISUAL ACUITY TEST.
AB  - BACKGROUND: Baseline visual acuity (VA) loss from static to dynamic head
      conditions assessed using the Dynamic Visual Acuity Testing (DVAT) have not been
      established in NCAA football players. DVAT assesses the Vestibulo-Ocular Reflex
      (VOR) which is measured in Logarithm of the Minimum Angle of Resolution (logMAR).
      Decreased VA beyond baseline measures may detect VOR impairment and impact
      treatment protocols and assist in return to play decisions post-concussion.
      HYPOTHESIS/PURPOSE: To establish normative VA mean scores during a static head
      posture as well as dynamically during the DVAT with a head speed of 150 deg/s in
      the pitch (vertical) and yaw (horizontal) planes rotating 20 degrees in each
      direction. STUDY DESIGN: Descriptive study, Diagnostic Tests. METHODS: Sixty
      seven, NCAA Division I College football players (age = 19.68 +/- 1.53) completed
      static VA and DVAT assessment in the pitch and yaw planes during baseline
      concussion testing at the beginning of the 2014 regular football season.
      Comparison of VA was evaluated by calculating the difference in players' static
      and dynamic VA values using the DVAT. RESULTS: Static VA for all participants
      (n=67) was -0.232 +/- 0.109 logMAR. Dynamic VA for participants (n=67) was 0.0845
      +/- 0.159 in pitch and -0.007 +/- 0.141 in yaw at 150 deg/sec. Mean losses in VA
      during pitch and yaw at 150 deg/sec were 0.317 +/- 0.140 and 0.227 +/- 0.133,
      respectively. CONCLUSIONS: VA diminishes during head movement at 150 degrees/sec.
      Loss of acuity beyond established normative values from baseline may be
      indicative of VOR dysfunction, especially secondary to head trauma. The
      assessment of visual acuity function with head movements of 150 deg/sec can
      potentially identify concussion and subsequent sequelae. Further research is
      recommended. LEVEL OF EVIDENCE: 2b.

PMID- 28515978
TI  - VARIATION IN MEDIAL AND LATERAL GASTROCNEMIUS MUSCLE ACTIVITY WITH FOOT POSITION.
AB  - BACKGROUND: The gastrocnemius has two heads, medial gastrocnemius (MG) and
      lateral gastrocnemius (LG); little is known how they contract with different foot
      positions. The MG is more frequently strained than the LG; and gastrocnemius
      activation pattern altered by foot position may play a role in injury. Leg
      exercises often use a toe-in versus toe-out foot position to isolate one
      gastrocnemius head over another. PURPOSE: The purpose of this study was to
      determine the electromyographic gastrocnemius muscle activity in the toe-out and
      toe-in foot positions during weight bearing and non-weight bearing activities.
      The hypothesis was that a toe-out foot position would elicit greater MG than LG
      activity; while the toe-in position would elicit greater activity in LG than MG
      in both weight bearing and non-weight bearing (NWB) positions. STUDY DESIGN: A
      cross-sectional study of young adults. METHODS: Thirty-three participants were
      recruited. Surface electrodes were placed on the bellies of the MG and LG. The
      gastrocnemius muscle was tested in toe-in and toe-out foot positions using two
      different tests: a standing heel-rise and resisted knee flexion while prone.
      Electromyographic activity was normalized against a MVIC during a heel raise with
      a neutral foot position. A 2x2x2 (Foot Position x Test Position x Muscle) ANOVA
      was used to determine if differences exist in activity between the MG and LG for
      toe-in versus toe-out standing and prone test positions. RESULTS: Significant
      test position main effect (F [1,32] = 86.9; p < .01), significant muscle main
      effect (F [1,32]=5.5; p < .01), and significant foot position x muscle
      interaction (F [1,32] = 14.58; p < .01) were found. Post hoc tests showed
      differences between MG and LG in toe-out position (t = 3.10; p < .01) but not in
      the toe-in for both test positions (t = 1.27; p = 0.21). CONCLUSIONS: With toe
      out, the MG was more active than LG in standing and prone; no difference was
      noted between MG and LG in toe-in for either position. LEVEL OF EVIDENCE: Level
      2.

PMID- 28515979
TI  - COMPARISON OF VIDEO-GUIDED, LIVE INSTRUCTED, AND SELF-GUIDED FOAM ROLL
      INTERVENTIONS ON KNEE JOINT RANGE OF MOTION AND PRESSURE PAIN THRESHOLD: A
      RANDOMIZED CONTROLLED TRIAL.
AB  - BACKGROUND: The use of foam rollers to provide tissue massage is a commonly used
      intervention by rehabilitation professionals for their patients and clients.
      Currently, there is no consensus on the optimal foam rolling treatment approach.
      Of particular interest are the effects of different instructional methods of foam
      rolling, as individuals ultimately perform these interventions independently
      outside of formal care. Finding the optimal instructional method may help improve
      the individual's understanding of the technique, allowing for a safe and
      effective intervention. PURPOSE: The purpose of this study was to compare the
      effects of video-guided, live instructed, and self-guided foam roll interventions
      on knee flexion Range of Motion (ROM) and pressure pain thresholds. METHODS:
      Forty-five healthy adults were recruited and randomly allocated to one of three
      intervention groups: video-guided, live-instructed, and self-guided. Each foam
      roll intervention lasted a total of 2 minutes. Dependent variables included knee
      flexion ROM and pressure pain threshold of the left quadriceps. Statistical
      analysis included subject demographic calculations and appropriate parametric and
      non-parametric tests to measure changes within and between intervention groups.
      RESULTS: Each intervention group showed significant gains in knee flexion ROM (p
      <= 0.003) and pressure pain thresholds (p < 0.001). An approximate 5 degree
      increase of knee flexion and a 150 kPa increase in pressure pain threshold was
      observed at the posttest measure for all groups. There was no significant
      difference (p=0.25) found between intervention groups. CONCLUSION: All three foam
      roll interventions showed short-term increases in knee flexion ROM and pressure
      pain thresholds. The two instructional methods (video and live instruction) and
      the self-guided method produced similar outcomes and can be used interchangeably.
      Individuals can benefit from various types of instruction and in cases of limited
      resources video may offer an alternative or adjunct to live instruction or an
      existing self-guided program. LEVEL OF EVIDENCE: 2c.

PMID- 28515975
TI  - PROSPECTIVE FUNCTIONAL PERFORMANCE TESTING AND RELATIONSHIP TO LOWER EXTREMITY
      INJURY INCIDENCE IN ADOLESCENT SPORTS PARTICIPANTS.
AB  - BACKGROUND: Due to the high number of adolescent athletes and subsequent lower
      extremity injuries, improvements of injury prevention strategies with emphasis on
      clinic-based and practical assessments are warranted. PURPOSE: The purpose of
      this study was to prospectively investigate if a battery of functional
      performance tests (FPT) could be used as a preseason-screening tool to identify
      adolescent athletes at risk for sports-related acute lower extremity injury via
      comparison of injured and uninjured subjects. METHODS: One hundred adolescent
      volleyball, basketball and soccer athletes (female, n=62; male, n=38; mean age =
      14.4 +/- 1.6) participated. The FPT assessment included: triple hop for distance,
      star excursion balance test, double leg lowering maneuver, drop jump video test,
      and multi-stage fitness test. Composite scores were calculated using a derived
      equation. Subjects were monitored throughout their designated sport season(s),
      which consisted of a six-month surveillance period. The schools certified
      athletic trainer (ATC) recorded all injuries. Subjects were categorized into
      groups according to sex and injury incidence (acute lower extremity injury vs.
      uninjured) for analysis. RESULTS: Mean FPT composite scores were significantly
      lower for the injured compared to the uninjured groups in both sexes (males:
      19.06 +/- 3.59 vs. 21.90 +/- 2.44; females: 19.48 +/- 3.35 vs. 22.10 +/- 3.06
      injured and uninjured, respectively)(p < .05). The receiver-operator
      characteristic analysis determined the cut-off score at <= 20 for both genders
      (sensitivity=.71, specificity=.81, for males; sensitivity=.67, specificity=.69,
      for females)(p<.05) for acute noncontact lower extremity injuries. Significant
      positive correlations were found between the FPT composite score and the multi
      stage fitness test in male subjects (r=.474, p=.003), suggesting a relationship
      between functional performance, aerobic capacity, and potential injury risk.
      CONCLUSION: A comprehensive assessment of functional performance tests may be
      beneficial to identify high-injury risk adolescents prior to athletic
      participation.

PMID- 28515984
TI  - IMPROVING THE REPORTING OF THERAPEUTIC EXERCISE INTERVENTIONS IN REHABILITATION
      RESEARCH.
AB  - : The foundation of evidence-based practice lies in clinical research, which is
      based on the utilization of the scientific method. The scientific method requires
      that all details of the experiment be provided in publications to support
      replication of the study in order to evaluate and validate the results. More
      importantly, clinical research can only be translated into practice when
      researchers provide explicit details of the study. Too often, rehabilitation
      exercise intervention studies lack the appropriate detail to allow clinicians to
      replicate the exercise protocol in their patient populations. Therefore, the
      purpose of this clinical commentary is to provide guidelines for optimal
      reporting of therapeutic exercise interventions in rehabilitation research. LEVEL
      OF EVIDENCE: 5.

PMID- 28515980
TI  - INVESTIGATING THE EFFECTIVENESS OF KINESIO(r) TAPING SPACE CORRECTION METHOD IN
      HEALTHY ADULTS ON PATELLOFEMORAL JOINT AND SUBCUTANEOUS SPACE.
AB  - BACKGROUND: Limited quantitative, physiological evidence exists regarding the
      effectiveness of Kinesio(r) Taping methods, particularly with respect to the
      potential ability to impact underlying physiological joint space and structures.
      To better understand the impact of these techniques, the underlying physiological
      processes must be investigated in addition to the examination of more subjective
      measures related to pain in unhealthy tissues. HYPOTHESIS/PURPOSE: The purpose of
      this study was to determine whether the Kinesio(r) Taping Space Correction Method
      created a significant difference in patellofemoral joint space, as quantified by
      diagnostic ultrasound. STUDY DESIGN: Pre-test/post-test prospective cohort study.
      METHODS: Thirty-two participants with bilaterally healthy knees and no past
      history of surgery took part in the study. For each participant, diagnostic
      ultrasound was utilized to collect three measurements: the patellofemoral joint
      space, the distance from the skin to the superficial patella, and distance from
      the skin to the patellar tendon. The Kinesio(r) Taping Space Correction Method
      was then applied. After a ten-minute waiting period in a non-weight bearing
      position, all three measurements were repeated. Each participant served as his or
      her own control. RESULTS: Paired t tests showed a statistically significant
      difference (mean difference = 1.1 mm, t[3,1] = 2.823, p = 0.008, g = .465)
      between baseline and taped conditions in the space between the posterior surface
      of the patella to the medial femoral condyle. Neither the distance from the skin
      to the superficial patella nor the distance from the skin to the patellar tendon
      increased to a statistically significant degree. CONCLUSIONS: The application of
      the Kinesio(r) Taping Space Correction Method increases the patellofemoral joint
      space in healthy adults by increasing the distance between the patella and the
      medial femoral condyle, though it does not increase the distance from the skin to
      the superficial patella nor to the patellar tendon. LEVEL OF EVIDENCE: 3.

PMID- 28515981
TI  - A SIX-WEEK SUPERVISED EXERCISE AND EDUCATIONAL INTERVENTION AFTER TOTAL HIP
      ARTHROPLASTY: A CASE SERIES.
AB  - BACKGROUND AND PURPOSE: Most rehabilitation interventions after total hip
      arthroplasty (THA) are not designed to return patients to high-levels of physical
      activity and, thus, low levels of physical activity and residual weakness are
      common. The purpose of this case series was to describe the feasibility and
      preliminary efficacy of an exercise and education intervention for patients after
      THA who have already completed formal outpatient physical therapy. STUDY DESIGN:
      Case series. CASE DESCRIPTION: Two participants underwent unilateral THA seven
      (case A) or eight (case B) months prior to the intervention. Individuals
      participated in 18 treatment sessions that included progressive aerobic and
      strengthening exercises and meetings with a health coach. Change in function,
      strength, and self-reported physical activity were measured. Outcomes 12 months
      after surgery were compared to a historical cohort of patients after THA.
      OUTCOME: There were no adverse events during the intervention. At the end of the
      intervention, hip and knee strength on the surgical side increased approximately
      30% compared to baseline in both cases. Activity level, and recreational
      performance, including walking up stairs and hiking uphill (case A), and running
      and golfing (case B), improved by the end of the intervention. Most changes were
      maintained at follow-up, although hip strength for case B decreased 27% after
      discharge from the intervention. Outcomes for both cases exceeded historical
      averages for patients 12 months after THA, with the exception of strength in case
      B. DISCUSSION: The exercise intervention was well tolerated and without negative
      effects in two participants. Both participants increased their ability to
      complete demanding recreational and sports-related activities, physical activity,
      and demonstrated improved hip abductor and knee extensor strength. Further
      research is needed to evaluate the implementation and effectiveness of similar
      interventions after THA. LEVEL OF EVIDENCE: Level 4.

PMID- 28515985
TI  - Epidemiological trends in skin cancer.
AB  - Skin cancer, including melanoma and non-melanoma skin cancer (NMSC), represents
      the most common type of malignancy in the white population. The incidence rate of
      melanoma is increasing worldwide, while the associated mortality remains stable,
      or is slightly decreasing. On the other hand, the incidence for NMSC varies
      widely, with the highest rates reported in Australia. In the current review, we
      highlight recent global trends in epidemiology of skin cancer. We discuss
      controversial issues raised in current epidemiological data, we analyze the most
      important risk factors associated with the development of melanoma and NMSC and
      the impact of skin cancer on health care services. Furthermore, we underline the
      pressing need for improved registration policies, especially for NMSC, and
      lastly, we refer to the ongoing primary and secondary prevention strategies and
      their outcomes so far.

PMID- 28515986
TI  - Use of and intentions to use dermoscopy among physicians in the United States.
AB  - BACKGROUND: Dermatologists routinely use dermoscopy to improve diagnostic
      accuracy of skin cancers. Much less is known about its use among other physicians
      who routinely examine the skin, such as family physicians, internists and plastic
      surgeons. OBJECTIVES: To document the use of dermoscopy in a sample of US
      physicians and to examine physician and practice characteristics associated with
      ever having used a dermascope and having some intentions to incorporate
      dermoscopy into clinical practice during the next 12 months. METHODS: From
      September 2015 to February 2016, we recruited 1,466 practicing physicians in
      person and online to complete an anonymous survey that assessed: demographic
      factors; physicians and practice characteristics; confidence differentiating skin
      lesions; knowledge and use of dermoscopy; and intentions and barriers to use
      dermoscopy. We conducted bivariate analysis to examine the relationship between
      key factors and the outcomes and entered the significant predictors into two
      separate logistic regressions. RESULTS: Fifteen percent of participants had ever
      used a dermascope and 6% were currently using it. Factors significantly
      associated with ever having used a dermascope (Model 1) and having intentions to
      use (Model 2) at the multivariate level were: recent graduation from medical
      school (strongest predictor in both models), identifying as a family physician,
      seeing a higher number of patients with skin cancer and having a higher level of
      confidence differentiating skin lesions. Both models were highly significant.
      CONCLUSION: Use of dermoscopy was low. Promotional efforts to increase dermoscopy
      use in the US are needed.

PMID- 28515988
TI  - The value of pre-surgical photography in the management of melanoma.

PMID- 28515982
TI  - CURRENT CONCEPTS ON THE GENETIC FACTORS IN ROTATOR CUFF PATHOLOGY AND FUTURE
      IMPLICATIONS FOR SPORTS PHYSICAL THERAPISTS.
AB  - CONTEXT: Recent advances within the field of genetics are currently changing many
      of the methodologies in which medicine is practiced. These advances are also
      beginning to influence the manner in which physical therapy services are
      rendered. Rotator cuff pathology is one of the most common diagnoses treated by
      the sports physical therapist. The purpose of this commentary is to educate
      sports physical therapists on the recent advances regarding how genetics
      influences rotator cuff pathology, including rotator cuff tears, and provide a
      perspective on how this information will likely influence post-operative shoulder
      rehabilitation in the near future. EVIDENCE ACQUISITION: A comprehensive review
      of the literature was completed using the Medline database along with individual
      searches of relevant physical therapy, surgical, cell biology, and sports
      medicine journals. Search terms included: shoulder, rotator cuff pathology,
      genetics, apoptosis, and physical therapy. Search results were compiled and
      evaluated; relevant primary studies and review articles were gathered; the
      results from this comprehensive review are summarized here. STUDY DESIGN:
      Clinical Commentary, Review of the Literature. RESULTS: Recent advances within
      the understanding of rotator cuff pathology have further elucidated the cellular
      and molecular mechanisms associated with rotator cuff tears. There appears to be
      a hypoxic-induced apoptotic cellular pathway that contributes to rotator cuff
      tears. Activation of specific proteins termed matrix metalloproteinases appear to
      be involved in not only primary rotator cuff tears, but also may influence the re
      tear rate after surgical intervention. Further advancements in the understanding
      of the cellular mechanisms contributing to rotator cuff tears and postoperative
      techniques to help prevent re-tears, may soon influence the methodology in which
      physical therapy services are provided to patients sustaining a rotator cuff
      injury. CONCLUSIONS: At this time continued research is required to more fully
      develop a comprehensive understanding of the role of genetic variables both
      within primary rotator cuff tears and their influences on post-operative
      rehabilitation from rotator cuff repair surgery. LEVEL OF EVIDENCE: Level 5.

PMID- 28515983
TI  - A CONCEPTUAL MODEL FOR PHYSICAL THERAPISTS TREATING ATHLETES WITH PROTRACTED
      RECOVERY FOLLOWING A CONCUSSION.
AB  - : Sports-related concussions are receiving growing attention in healthcare. Most
      concussions resolve spontaneously with little or no treatment, but twenty percent
      of concussions take longer than three weeks to resolve. In some cases, symptoms
      can last for five years following a traumatic brain injury. Physical Therapists
      have unique skills that can assist patients experiencing protracted recovery. The
      purpose of this clinical commentary is to describe a new conceptual model that
      provides a framework for Physical Therapy management of patients with protracted
      recovery following a sports-related concussion. The end product is a visual
      diagram that represents the full scope of clinical practice that Physical Therapy
      can provide to an athlete following a concussion. LEVEL OF EVIDENCE: 5.

PMID- 28515987
TI  - The need for improved dermoscopy training in residency: a survey of US
      dermatology residents and program directors.
AB  - BACKGROUND: Inadequate dermoscopy training represents a major barrier to proper
      dermoscopy use. OBJECTIVE: To better understand the status of dermoscopy training
      in US residency programs. METHODS: A survey was sent to 417 dermatology residents
      and 118 program directors of dermatology residency programs. RESULTS: Comparing
      different training times for the same training type, residents with 1-10 hours of
      dedicated training had similar confidence using dermoscopy in general (p = 1.000)
      and satisfaction with training (p = .3224) than residents with >10 hours of
      dedicated training. Comparing similar training times for different training
      types, residents with 1-10 hours of dedicated training had significantly
      increased confidence using dermoscopy in general (p = .0105) and satisfaction
      with training (p = .0066) than residents with 1-10 hours of only bedside
      training. Lastly, residents with 1-10 hours of dedicated training and >10 hours
      of dedicated training had significantly increased confidence using dermoscopy in
      general (p = .0002, p = .2471) and satisfaction with training (p <.0001, p <
      .0001) than residents with no dermoscopy training at all. CONCLUSIONS: Dermoscopy
      training in residency should include formal dermoscopy training that is overseen
      by the program director and is possibly supplemented by outside dermoscopy
      training.

PMID- 28515990
TI  - Topical mycophenolate mofetil in the treatment of vitiligo: a pilot study.
AB  - BACKGROUND: Vitiligo is a multifactorial disease that is characterized by
      circumscribed depigmented macules and patches. Autoimmune reactions may play an
      important role in the pathogenesis of the disease. Mycophenolate mofetil is a
      drug that inhibits DNA synthesis in lymphocytes and has been used in autoimmune
      diseases such as immunobullous skin diseases, lupus erythematosus, and autoimmune
      hepatitis. OBJECTIVES: The objective of this study was to show the efficacy of
      topical mycophenolate mofetil in the treatment of vitiligo. METHODS: Thirty
      patients with limited vitiligo were enrolled in this study. The patients applied
      a topical preparation of mycophenolate mofetil 15% twice daily for three months
      and at the end of every month, repigmentation was assessed using the Vitiligo
      Area Scoring Index (VASI). RESULTS: At the end of the third month, 36.6 % (n=11)
      of the patients showed about 25% repigmentation of the lesions. No side effects
      were observed throughout the study. CONCLUSION: This study showed that topical
      mycophenolate mofetil can be somewhat effective in the treatment of vitiligo;
      however, it seems to be inferior to potent topical steroids in inducing
      repigmentation.

PMID- 28515989
TI  - Laugier-Hunziker syndrome: a case of asymptomatic mucosal and acral
      hyperpigmentation.
AB  - Laugier-Hunziker syndrome (LHS) is a rare condition characterized by acquired
      hyperpigmentation involving the lips, oral mucosa, acral surfaces, nails and
      perineum. While patients with LHS may manifest pigmentation in all of the
      aforementioned areas, most present with pigmentation localized to only a few of
      these anatomical sites. We herein report a patient exhibiting the characteristic
      pigment distribution pattern associated with LHS. Since LHS is a diagnosis based
      on exclusion, we discuss the differential diagnosis of mucocutaneous
      hyperpigmentation. Due to the benign nature of the disease, it is critical to
      differentiate this disorder from conditions with similar mucocutaneous pigmentary
      changes with somatic abnormalities that require medical management. We also
      explore potential mechanisms that may explain the pathogenesis of LHS.

PMID- 28515991
TI  - Non-follicular milky globules-dermoscopy saves the day.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous
      adverse reaction caused mostly by medication. Early diagnosis is important as
      initiation of supportive treatment and avoidance of drug is of prime importance.
      A young male presented with an erythematous rash after taking diclofenac for
      pain. Polarized dermoscopy revealed milky globules on a uniform reddish
      background sparing the follicles, which confirmed the diagnosis of AGEP.

PMID- 28515992
TI  - Dermoscopy of cutaneous lymphangioma circumscriptum.
AB  - Lymphangiomas are congenital lymphatic malformations. They are clinically
      characterized by clusters of translucent vesicles, and on dermoscopy, yellow
      lacunae surrounded by pale septa as well as reddish to bluish lacunae have been
      described. A young male presented with a seven-year history of a vesicular
      lesion. Dermoscopy revealed multiple white-yellowish well-circumscribed roundish
      areas (lacunae) surrounded by pale septa. A few lacunae contained blood, which
      was characteristically accumulated in the lowest part of the lacuna, resulting in
      an appearance similar to the so-called "hypopyon" of the eye. We suggest a new
      "dermatologic" metaphoric term to desrcibe this peculiar feature (half-and-half
      lacuna).

PMID- 28515993
TI  - Triage amalgamated dermoscopic algorithm (TADA) for skin cancer screening.
AB  - IMPORTANCE: Dermoscopic triage algorithms have been shown to improve beginners'
      abilities for identifying pigmented skin lesions requiring biopsy. OBJECTIVE: To
      estimate the diagnostic accuracy of the Triage Amalgamated Dermoscopic Algorithm
      (TADA) for pigmented and nonpigmented skin cancers. Secondarily, to compare TADAs
      performance to those of existing triage algorithms for the identification of
      pigmented skin cancers. DESIGN: Cross-sectional, observational, reader study that
      took place at a beginner and intermediate level dermoscopy course. PARTICIPANTS:
      Two hundred medical professionals of various specialties attended the course and
      120 voluntarily joined the study (60% participation rate). EXPOSURES: After
      receiving basic dermoscopy training, participants evaluated 50 polarized,
      dermoscopic images of pigmented (22 benign, 18 malignant) and nonpigmented (1
      benign, 9 malignant) skin lesions using TADA. Pigmented lesions were also
      evaluated using the Three-Point Checklist and AC Rule. With TADA, participants
      first determined if a lesion was an unequivocal angioma, dermatofibroma, or
      seborrheic keratosis, which would exclude it from further evaluation. All other
      lesions were assessed for architectural disorder, starburst pattern, blue-black
      or gray color, shiny white structures, negative network, ulcer/erosion, or
      vessels. Any one feature indicated suspicion for malignancy. RESULTS: Most
      participants were dermatologists (n=64, 53.3%) or primary care physicians (n=41,
      34.2%), and many lacked previous dermoscopy training (n=52, 43.3%). TADA's
      sensitivity and specificity for all skin cancers was 94.6% (95% CI=93.4-95.7%)
      and 72.5% (95% CI=70.1-74.7%), respectively. For pigmented skin cancers, the
      sensitivity and specificity were 94.0% (95% CI=92.9-95.0%) and 75.5% (95% CI=73.8
      77.2%). This compared to 71.9% (95%CI=69.8-73.9%) and 81.4% (95%CI=79.7-83.0%)
      for the Three-Point Checklist and 88.6% (95%CI=87.1-89.9%) and 78.7% (95%CI=76.9
      80.3%) for the AC Rule. CONCLUSIONS: These results suggest that TADA compares
      favorably to existing triage algorithms and might be a useful triage tool with
      high sensitivity and specificity for pigmented and nonpigmented skin cancers.
      Further studies are needed to validate these preliminary observations.

PMID- 28515994
TI  - In vivo reflectance confocal microscopy: a useful non-invasive tool to assess the
      response to isolated limb perfusion for superficial pigmented melanoma in-transit
      metastatic disease. Report of a case.
AB  - Complete response can be difficult to assess after isolated limb perfusion (ILP)
      for metastatic in-transit melanoma, especially when numerous and unresectable
      post-necrotic persisting pigmented lesions occur. These residual lesions are
      mainly seen in the more superficial and pigmented types of metastatic disease and
      correspond to the residual melanophage granuloma that persists after tumor
      tissues undergo complete necrosis. Reflectance confocal microscopy (RCM) is a non
      invasive technique that allows the exploration of the superficial dermis. Here,
      we present the case of a patient in whom numerous post-ILP limb residual
      pigmented lesions were explored using combined RCM and histological examination
      of sample lesions and could be characterized as non-active. This approach allowed
      us to avoid additional excisions.

PMID- 28515996
TI  - Dermoscopy of alopecia areata-a retrospective analysis.
AB  - BACKGROUND: Dermoscopy devices can overcome the refractive properties of stratum
      corneum by interface medium or cross polarization such that the lesion can be
      easily seen. AIM: To examine the dermoscopic feature in alopecia areata and
      correlate the severity of disease with dermoscopic features. MATERIALS AND
      METHODS: Retrospective analysis of 72 patients suffering from alopecia areata
      (AA), irrespective of age and sex, who visited the dermatology outpatient
      department of a tertiary care center in Eastern India was carried out. The most
      recently developed cases of AA were examined dermoscopically. Variables included
      yellow dots (YDs), black dots (BDs), broken hair (BH), short vellus hair (SVH),
      and exclamation mark hair (EMH) on the basis of available literature and
      expertise. RESULTS: Yellow dots was the most common finding seen in 57 cases
      (79.16%), black dots in 51 cases (70.8%). Short vellus hair was seen in 32 cases
      (44.44%), broken hair was seen in 31 cases (43.05%), and exclamation mark hair in
      23 cases (31.9%). YDs per field of vision was considered as the most common
      finding with increased severity of AA. CONCLUSION: YDS, in increased number per
      field of vision, is the most consistent finding seen in severe cases of AA, as
      they are in progressive AA and alopecia universalis. An increased number of SVH
      and terminal hairs were seen in patients who were being treated.

PMID- 28515995
TI  - Dermoscopy and reflectance confocal microscopy in pedunculated basal cell
      carcinoma.
AB  - There have been limited cases of pedunculated basal cell carcinoma (BCC) reported
      in the literature. The dermoscopic features were described in only one of them.
      However, not one of them described the confocal microscopy features. In this
      report we presented a case of pedunculated basal cell carcinoma (BCC) with
      dermoscopic and reflectance confocal microscopy features.

PMID- 28515997
TI  - Primary myxoid melanoma with dermoscopic findings.
AB  - Myxoid melanoma is a rare variant of melanoma, which is characterized by atypical
      spindle cells and dense mucin deposition in dermis. This tumor is usually seen in
      elderly people with a similar progress in other variants of melanoma. A 28-year
      old male presented to our outpatient clinic with a 6-month history of a slowly
      growing asymptomatic pink lesion on his arm. Dermoscopic examination revealed
      pink-white cristalline structures and blue-grayish ovoid globules. The lesion was
      totally excised with initial diagnosis of basosquamous carcinoma, amelanotic
      melanoma and basal cell carcinoma. Histopathological examination was consistent
      with myxoid melanoma. We present this case due to the rarity of myxoid melanoma
      and occurrence at such a young age.

PMID- 28515998
TI  - Dermoscopy of histoid leprosy: a case report.

PMID- 28515999
TI  - Acute onset of a severe rash on the face and dorsal hands.

PMID- 28516001
TI  - Validity, Usefulness and Cost of RETeval System for Diabetic Retinopathy
      Screening.
AB  - PURPOSE: We studied the validity, usefulness, and relative cost to detect
      diabetic retinopathy (DR) and sight-threatening DR (STDR) by using a hand-held
      electrophysiologic tool compared to digital fundus photography. METHOD: Patients
      with diabetes attending the screening unit of King Khaled Eye Specialist
      Hospital, Riyadh, Saudi Arabia were evaluated by "RETeval", Amsler grid, and
      digital dilated fundus photography. Fundus images were evaluated by a retina
      specialist to determine grade of DR. The sensitivity and specificity of STDR and
      DR screening compared to photography were calculated, as well as "RETeval"
      combined with Amsler grid testing. The area under the curve (AUC) of "RETeval"
      screening outcome was calculated. RESULT: We analyzed data of 400 diabetic
      patients. The prevalence of DR of any grade was 48.8% (95% confidence interval
      [CI], 43.9-53.7) while the prevalence of STDR was 27% (95% CI, 22.6-31.4). The
      outcome of RETeval test was "fail" (based on 20 MUV or more amplitude of
      electrophysiologic spikes) in 351 (87.8%; 95% CI, 84.5-91.0) eyes. The
      sensitivity of the device was 95.4% and the specificity was 17.5%. Thus, the
      sensitivity of sequential testing with RETeval and Amsler grid test was 30.1% and
      the specificity was 80.1%. The AUCs for STDR and DR in general were 76.6% and
      50.6%, respectively. CONCLUSIONS: "RETeval" is a rapid screening device with
      excellent sensitivity for detecting STDR. It has potential as a first level
      screening tool to detect patients who require further evaluation. TRANSLATIONAL
      RELEVANCE: Retinal function, such as electrophysiology, can be used as a new
      concept for screening for DR.

PMID- 28516002
TI  - Transplantation of Human Embryonic Stem Cell-Derived Retinal Cells into the
      Subretinal Space of a Non-Human Primate.
AB  - PURPOSE: Previous studies have demonstrated the ability of retinal cells derived
      from human embryonic stem cells (hESCs) to survive, integrate into the host
      retina, and mediate light responses in murine mouse models. Our aim is to
      determine whether these cells can also survive and integrate into the retina of a
      nonhuman primate, Saimiri sciureus, following transplantation into the subretinal
      space. METHODS: hESCs were differentiated toward retinal neuronal fates using our
      previously published technique and cultured for 60 to 70 days. Differentiated
      cells were further treated with 20 MUM N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S
      phenylglycine t-butyl ester (DAPT) for a period of 5 days immediately prior to
      subretinal transplantation. Differentiated cells were labeled with a lentivirus
      expressing GFP. One million cells (10,000 cells/MUL) were injected into the
      submacular space into a squirrel monkey eye, using an ab externo technique.
      RESULTS: RetCam imaging demonstrated the presence and survival of human donor
      cells 3 months after transplantation in the S. sciureus eye. Injected cells
      consolidated in the temporal macula. GFP+ axonal projections were observed to
      emanate from the central consolidation of cells at 1 month, with some projecting
      into the optic nerve by 3 months after transplantation. CONCLUSIONS: Human ES
      cell-derived retinal neurons injected into the submacular space of a squirrel
      monkey survive at least 3 months postinjection without immunosuppression. Some
      donor cells appeared to integrate into the host inner retina, and numerous donor
      axonal projections were noted throughout, with some projecting into the optic
      nerve. TRANSLATIONAL RELEVANCE: These data illustrate the feasibility of hESC
      derived retinal cell replacement in the nonhuman primate eye.

PMID- 28516000
TI  - Role of a Dual Splicing and Amino Acid Code in Myopia, Cone Dysfunction and Cone
      Dystrophy Associated with L/M Opsin Interchange Mutations.
AB  - PURPOSE: Human long (L) and middle (M) wavelength cone opsin genes are highly
      variable due to intermixing. Two L/M cone opsin interchange mutants, designated
      LIAVA and LVAVA, are associated with clinical diagnoses, including red-green
      color vision deficiency, blue cone monochromacy, cone degeneration, myopia, and
      Bornholm Eye Disease. Because the protein and splicing codes are carried by the
      same nucleotides, intermixing L and M genes can cause disease by affecting
      protein structure and splicing. METHODS: Genetically engineered mice were created
      to allow investigation of the consequences of altered protein structure alone,
      and the effects on cone morphology were examined using immunohistochemistry. In
      humans and mice, cone function was evaluated using the electroretinogram (ERG)
      under L/M- or short (S) wavelength cone isolating conditions. Effects of LIAVA
      and LVAVA genes on splicing were evaluated using a minigene assay. RESULTS: ERGs
      and histology in mice revealed protein toxicity for the LVAVA but not for the
      LIAVA opsin. Minigene assays showed that the dominant messenger RNA (mRNA) was
      aberrantly spliced for both variants; however, the LVAVA gene produced a small
      but significant amount of full-length mRNA and LVAVA subjects had correspondingly
      reduced ERG amplitudes. In contrast, the LIAVA subject had no L/M cone ERG.
      CONCLUSIONS: Dramatic differences in phenotype can result from seemingly minor
      differences in genotype through divergent effects on the dual amino acid and
      splicing codes. TRANSLATIONAL RELEVANCE: The mechanism by which individual
      mutations contribute to clinical phenotypes provides valuable information for
      diagnosis and prognosis of vision disorders associated with L/M interchange
      mutations, and it informs strategies for developing therapies.

PMID- 28516005
TI  - Caffey's Disease Sans Mandibular and Clavicular Involvement: A Rare Case Report.
AB  - Caffey's disease, also known as Infantile Cortical Hyperostosis, is a rare, self
      limited, benign, inflammatory gene-related disorder of infants that causes bone
      changes, soft tissue swelling, and irritability. The mandible (75%), clavicles,
      and ulnae are the bones most frequently involved, others being long bones,
      lateral ribs, ilia with skull being the rarest. However, we report a case of a 5
      month-old male diagnosed with Infantile cortical hyperostosis but with absent
      mandibular and clavicular involvement, thus depicting the unusual presentation of
      this disease.

PMID- 28516004
TI  - Endoscopic Ultrasound: Reaching Where Others Can't.
AB  - Endoscopic ultrasound (EUS) has been increasingly used for the diagnosis and
      staging of pancreatic cancer. It has recently become the modality of choice in
      assessing pancreatic lesions overcoming other traditional modalities. Typically
      lesions located at the tail of the pancreas are best accessed through the
      stomach. We present a patient with pancreatic tail mass occurring in the setting
      of a large hiatal hernia, intrathoracic stomach, and severe lumbar levoscoliosis.
      Due to altered anatomy and extensive vascular connections of the mass, any
      surgical or radiological intervention was considered high risk for the patient.
      EUS was the only modality capable of providing a pancreatic mass tissue sample in
      this patient with challenging thoraco-abdominal anatomy. Moreover, pancreatic
      tail lesions are traditionally best accessed through the gastric fundus; however,
      in view of the patient's altered anatomy, EUS-fine needle aspiration (FNA) had to
      be performed through the duodenum. This case raises the importance of EUS when
      surgical and radiological interventions are restricted.

PMID- 28516003
TI  - Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R against
      Escherichia coli.
AB  - Efflux pump inhibitors are of great interest since their use as adjuvants of
      bacterial chemotherapy can increase the intracellular concentrations of the
      antibiotics and assist in the battle against the rising of antibiotic-resistant
      bacteria. In this work, we have described the mode of action of the 2
      phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4
      propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its
      efflux inhibitory ability, its synergistic activity in combination with
      antibiotics, and compared its effects with the inhibitors phenyl-arginine-beta
      naphthylamide (PAbetaN) and chlorpromazine (CPZ). The results showed that PQQ4R
      acts synergistically, in a concentration dependent manner, with antibiotics known
      to be subject to efflux in E. coli reducing their MIC in correlation with the
      inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R
      at sub-inhibitory concentrations promote the intracellular accumulation of
      ethidium bromide inhibiting its efflux similarly to PAbetaN or CPZ, well-known
      and described efflux pump inhibitors for Gram-negative bacteria and whose
      clinical usage is limited by their levels of toxicity at clinical and
      bacteriological effective concentrations. The time-kill studies showed that
      PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity
      associated with a fast decrease of the intracellular ATP levels. The results also
      indicated that the mode of action of PQQ4R involves the destabilization of the E.
      coli inner membrane potential and ATP production impairment, ultimately leading
      to efflux pump inhibition by interference with the energy required by the efflux
      systems. At bactericidal concentrations, membrane permeabilization increases and
      finally ATP is totally depleted leading to cell death. Since drug resistance
      mediated by the activity of efflux pumps depends largely on the proton motive
      force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future
      adjuvants of conventional therapy against E. coli and other Gram-negative
      bacteria, especially their multidrug resistant forms. Their major limitation is
      the high toxicity for human cells at the concentrations needed to be effective
      against bacteria. Their future molecular optimization to improve the efflux
      inhibitory properties and reduce relative toxicity will optimize their potential
      for clinical usage against multi-drug resistant bacterial infections due to
      efflux.

PMID- 28516006
TI  - Hydrogel formation by multivalent IDPs: A reincarnation of the microtrabecular
      lattice?
AB  - Based on high-voltage electron microscopic (HVEM) data of fixed cultured cells,
      an elaborate three-dimensional network of filaments, including and
      interconnecting other elements of the cytoskeleton, was observed in cells some
      half a century ago. Despite many attempts and comparative studies, this
      "microtrabecular lattice" (MTL) of the cytoplasmic ground substance could not be
      established as a genuine component of the eukaryotic cell, and is mostly
      considered today as a sample-preparation artifact of protein adherence and cross
      linking to the cytoskeleton. Here we elaborate on the provocative idea that
      recent observations of hydrogel-forming phase transitions of repetitive regions
      of intrinsically disordered proteins (IDPs) bear resemblance in creation,
      organization and physical appearance to the MTL. We review this phenomenon in
      detail, and suggest that phase transitions of actin regulatory proteins,
      neurofilament side-arms and other proteins could generate non-uniform spatial
      distribution of cytoplasmic material in the vicinity of the cytoskeleton that
      might even give rise to fixation phenomena resembling the MTL. Whether such
      hydrogel formation by IDPs is a general physical phenomenon, will remain to be
      seen, nevertheless, the underlying organizational principle provokes novel
      experimental studies to uncover the ensuing higher-level regulation of cell
      physiology, in which the despised and long-forgotten concept of MTL might give
      some interesting leads.

PMID- 28516007
TI  - What's in a name? Why these proteins are intrinsically disordered: Why these
      proteins are intrinsically disordered.
AB  - "What's in a name? That which we call a rose By any other name would smell as
      sweet." From "Romeo and Juliet", William Shakespeare (1594) This article opens a
      series of publications on disambiguation of the basic terms used in the field of
      intrinsically disordered proteins. We start from the beginning, namely from the
      explanation of what the expression "intrinsically disordered protein" actually
      means and why this particular term has been chosen as the common denominator for
      this class of proteins characterized by broad structural, dynamic and functional
      characteristics.

PMID- 28516009
TI  - MFDp2: Accurate predictor of disorder in proteins by fusion of disorder
      probabilities, content and profiles.
AB  - Intrinsically disordered proteins (IDPs) are either entirely disordered or
      contain disordered regions in their native state. IDPs were found to be abundant
      in complex organisms and implicated in numerous cellular processes. Experimental
      annotation of disorder lags behind the rapidly growing sizes of the protein
      databases, and thus computational methods are used to close this gap and to
      investigate the disorder. MFDp2 is a novel content-rich and user-friendly web
      server for sequence-based prediction of protein disorder that builds upon our
      residue-level disorder predictor MFDp and chain-level disorder content predictor
      DisCon. It applies novel post-processing filters and uses sequence alignment to
      improve predictive quality. Using a new benchmark data set, which has reduced
      sequence identity to corresponding training data sets, MFDp2 is shown to provide
      competitive predictive quality when compared with MFDp and a comprehensive set of
      13 other state-of-the-art predictors, including publicly available versions of
      the top predictors from CASP9. Our server obtains the highest Mathews Correlation
      Coefficient (MCC) and the second best Area Under the receiver operating
      characteristic Curve (AUC). In addition to the disorder predictions, our server
      also outputs well-described sequence-derived information that allows profiling
      the predicted disorder. We conveniently visualize sequence conservation,
      predicted secondary structure, relative solvent accessibility and alignments to
      chains with annotated disorder. We allow predictions for multiple proteins at the
      same time and each prediction can be downloaded as text-based (parsable) file.
      The web server, which includes help pages and tutorial, is freely available at
      biomine.ece.ualberta.ca/MFDp2/.

PMID- 28516008
TI  - The alphabet of intrinsic disorder: I. Act like a Pro: On the abundance and roles
      of proline residues in intrinsically disordered proteins.
AB  - A significant fraction of every proteome is occupied by biologically active
      proteins that do not form unique three-dimensional structures. These
      intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) have essential
      biological functions and are characterized by extensive structural plasticity.
      Such structural and functional behavior is encoded in the amino acid sequences of
      IDPs/IDPRs, which are enriched in disorder-promoting residues and depleted in
      order-promoting residues. In fact, amino acid residues can be arranged according
      to their disorder-promoting tendency to form an alphabet of intrinsic disorder
      that defines the structural complexity and diversity of IDPs/IDPRs. This review
      is the first in a series of publications dedicated to the roles that different
      amino acid residues play in defining the phenomenon of protein intrinsic
      disorder. We start with proline because data suggests that of the 20 common amino
      acid residues, this one is the most disorder-promoting.

PMID- 28516011
TI  - Functional fragments of disorder in outer membrane beta barrel proteins.
AB  - The traditional view of "sequence-structure-function" has been amended by the
      discovery of intrinsically disordered proteins. Almost 50% of PDB structures are
      now known to have one or more regions of disorder, which are involved in diverse
      functions. These regions typically possess low aromatic content and sequence
      complexity as well as high net charge and flexibility. In this study, we examined
      the composition and contribution of intrinsic disorder in outer membrane beta
      barrel protein functions. Our systematic analysis to find the dual personality
      (DP) fragments, which often function by disorder-order transitions, revealed the
      presence of 61 DP fragments with 234 residues in beta barrel trans membrane
      protein structures. It was found that though the disorder is more prevalent in
      the periplasmic regions, most of the residues which undergo disorder-order
      transitions are found in the extracellular regions. For example, the calcium
      binding sites in BtuB protein are found to undergo disorder to order transition
      upon binding calcium. The conformational change in the cell receptor binding site
      of the OpcA protein, which is important in host cell interactions of N.
      meningitidis, was also found to be due to the disorder-order transitions
      occurring in the presence of the ligand. The natively disordered nature of DP
      fragments makes it more appropriate to call them "functional fragments of
      disorder." The present study provides insight into the roles played by
      intrinsically disordered regions in outer membrane protein functions.

PMID- 28516013
TI  - SS-map: Visualizing cooperative secondary structure elements in protein
      ensembles.
AB  - We present SS-map, a tool to visualize the secondary structure content of
      ensembles of proteins. When generating ensembles of intrinsically disordered
      proteins, we lose the understanding a single native structure gives for folded
      proteins. It then becomes difficult to visualize the composition of the ensembles
      or to detect transient helices such as MoRFs. Conformational propensities for
      single residues also hide the nature of cooperative structures. Here we show how
      SS-map describes folded and unfolded ensembles of some peptides and gives a new
      view of the ensembles used to describe intrinsically disordered proteins with
      residual structure in computational and NMR experiments. This tool is implemented
      in an open-source python code located at code.google.com/p/ss-map.

PMID- 28516014
TI  - A method to trap transient and weak interacting protein complexes for structural
      studies.
AB  - Several key biological events adopt a "hit-and-run" strategy in their transient
      interactions between binding partners. In some instances, the disordered nature
      of one of the binding partners severely hampers the success of co
      crystallization, often leading to the crystallization of just one of the
      partners. Here, we discuss a method to trap weak and transient protein
      interactions for crystallization. This approach requires the structural details
      of at least one of the interacting partners and binding knowledge to dock the
      known minimum binding region (peptide) of the protein onto the other using an
      optimal-sized linker. Prior to crystallization, the purified linked construct
      should be verified for its intact folding and stability. Following structure
      determination, structure-guided functional studies are performed with
      independent, full-length unlinked proteins to validate the findings of the linked
      complex. We designed this approach and then validated its efficacy using a 24
      amino acid minimum binding region of the intrinsically disordered, neuron
      specific substrates, Neurogranin and Neuromodulin, joined via a Gly-linker to
      their interacting partner, Calmodulin. Moreover, the reported functional studies
      with independent full-length proteins confirmed the findings of the linked
      peptide complexes. Based on our studies, and in combination with the supporting
      literature, we suggest that optimized linkers can provide an environment to mimic
      the natural interactions between binding partners, and offer a useful strategy
      for structural studies to trap weak and transient interactions involved in
      several biological processes.

PMID- 28516010
TI  - The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered
      and intrinsically disordered proteins.
AB  - The ability of a protein to fold into unique functional state or to stay
      intrinsically disordered is encoded in its amino acid sequence. Both ordered and
      intrinsically disordered proteins (IDPs) are natural polypeptides that use the
      same arsenal of 20 proteinogenic amino acid residues as their major building
      blocks. The exceptional structural plasticity of IDPs, their capability to exist
      as heterogeneous structural ensembles and their wide array of important disorder
      based biological functions that complements functional repertoire of ordered
      proteins are all rooted within the peculiar differential usage of these building
      blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder
      promoting residues) are noticeably more common in IDPs than in sequences of
      ordered proteins, which, in their turn, are enriched in several order-promoting
      residues. Furthermore, residues can be arranged according to their "disorder
      promoting potencies," which are evaluated based on the relative abundances of
      various amino acids in ordered and disordered proteins. This review continues a
      series of publications on the roles of different amino acids in defining the
      phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the
      second most disorder-promoting residue.

PMID- 28516016
TI  - Structural characterizations of phosphorylatable residues in transmembrane
      proteins from Arabidopsis thaliana.
AB  - Phosphorylation is a common post-translational modification that plays important
      roles in a wide range of biochemical and cellular processes. Many enzymes and
      receptors can be switched "on" or "off" by conformational changes induced by
      phosphorylation. The phosphorylation process is mediated by a family of enzymes
      called kinase. Currently, more than 1,000 different kinases have been identified
      in Arabidopsis thaliana proteome. Kinases interact with each other and with many
      regulatory proteins forming phosphorylation networks. These phosphorylation
      networks modulate the signaling processes and control the functions of cells.
      Normally, kinases phosphorylate serines, threonines, and tyrosines. However, in
      many proteins, not all of these 3 types of amino acids can be phosphorylated.
      Therefore, identifying the phosphorylation sites and the possible phosphorylation
      events is very important in decoding the processes of regulation and the function
      of phosphorylation networks. In this study, we applied computational and
      bioinformatics tools to characterize the association between phosphorylation
      events and structural properties of corresponding proteins by analyzing more than
      50 trans-membrane proteins from Arabidopsis thaliana. In addition to the
      previously established conclusion that phosphorylation sites are closely
      associated with intrinsic disorder, we found that the phosphorylation process may
      also be affected by solvent accessibility of phosphorylation sites and further
      promoted by neighboring modification events.

PMID- 28516012
TI  - Extracting structural information from charge-state distributions of
      intrinsically disordered proteins by non-denaturing electrospray-ionization mass
      spectrometry.
AB  - Intrinsically disordered proteins (IDPs) exert key biological functions but tend
      to escape identification and characterization due to their high structural
      dynamics and heterogeneity. The possibility to dissect conformational ensembles
      by electrospray-ionization mass spectrometry (ESI-MS) offers an attracting
      possibility to develop a signature for this class of proteins based on their
      peculiar ionization behavior. This review summarizes available data on charge
      state distributions (CSDs) obtained for IDPs by non-denaturing ESI-MS, with
      reference to globular or chemically denatured proteins. The results illustrate
      the contributions that direct ESI-MS analysis can give to the identification of
      new putative IDPs and to their conformational investigation.

PMID- 28516015
TI  - Digested disorder: Quarterly intrinsic disorder digest (January/February/March,
      2013).
AB  - The current literature on intrinsically disordered proteins is blooming. A simple
      PubMed search for "intrinsically disordered protein OR natively unfolded protein"
      returns about 1,800 hits (as of June 17, 2013), with many papers published quite
      recently. To keep interested readers up to speed with this literature, we are
      starting a "Digested Disorder" project, which will encompass a series of reader's
      digest type of publications aiming at the objective representation of the
      research papers and reviews on intrinsically disordered proteins. The only two
      criteria for inclusion in this digest are the publication date (a paper should be
      published within the covered time frame) and topic (a paper should be dedicated
      to any aspect of protein intrinsic disorder). The current digest covers papers
      published during the period of January, February and March of 2013. The papers
      are grouped hierarchically by topics they cover, and for each of the included
      paper a short description is given on its major findings.

PMID- 28516019
TI  - Hydrogen skeleton, mobility and protein architecture.
AB  - The mobility of the proton-proton radial vectors is introduced as a quantitative
      measure for the structural dynamics of organic materials, especially protein
      molecules. As defined for the entire molecule, the hydrogen mobility (HM) is
      proposed as an "order parameter," which describes the effect of motional
      narrowing on inter-proton dipole-dipole interactions. HM satisfies all
      requirements of an order parameter in the Landau molecular field theory of phase
      transitions. The wide-line NMR second moments needed to obtain HM are exactly
      defined and measurable physical quantities, which are not produced by
      mathematical fitting and do not carry the limitations and restrictions of any
      model (theoretical formalism). We first demonstrate the usefulness of HM on small
      organic molecules with data taken form the literature. We outline its link with
      structural and functional characteristics on a range of proteins: HM provides a
      model-free parameter based on first principles that can clearly distinguish
      between globular and intrinsically disordered proteins, and can also provide
      insight into the behavior of disease-related mutants.

PMID- 28516020
TI  - Understanding the molecular mechanisms underlying complex cancer genome
      rearrangements.
AB  - In their recent paper, Malhotra et al. performed a comprehensive analysis of the
      structural variation breakpoints in 64 cancer genomes from 7 tumor types to find
      the prevalence and origins of complex genomic rearrangements.1 Since this work
      represents a breakthrough in understanding of the molecular mechanisms underlying
      complex cancer genome rearrangements, we provide a brief overview of this
      outstanding study.

PMID- 28516017
TI  - Distribution and cluster analysis of predicted intrinsically disordered protein
      Pfam domains.
AB  - The Pfam database groups regions of proteins by how well hidden Markov models
      (HMMs) can be trained to recognize similarities among them. Conservation pressure
      is probably in play here. The Pfam seed training set includes sequence and
      structure information, being drawn largely from the PDB. A long standing
      hypothesis among intrinsically disordered protein (IDP) investigators has held
      that conservation pressures are also at play in the evolution of different kinds
      of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not
      always conserved across Pfam domains. Here we analyze distributions and clusters
      of PID regions in 193024 members of the version 23.0 Pfam seed database. To
      include the maximum information available for proteins that remain unfolded in
      solution, we employ the 10 linearly independent Kidera factors1-3 for the amino
      acids, combined with PONDR4 predictions of disorder tendency, to transform the
      sequences of these Pfam members into an 11 column matrix where the number of rows
      is the length of each Pfam region. Cluster analyses of the set of all regions,
      including those that are folded, show 6 groupings of domains. Cluster analyses of
      domains with mean VSL2b scores greater than 0.5 (half predicted disorder or more)
      show at least 3 separated groups. It is hypothesized that grouping sets into
      shorter sequences with more uniform length will reveal more information about
      intrinsic disorder and lead to more finely structured and perhaps more accurate
      predictions. HMMs could be trained to include this information.

PMID- 28516018
TI  - Hypothesis: The unfolding power of protein dielectricity.
AB  - A hypothesis is proposed on a potential role of protein dielectricity as an
      unfolding factor in protein-protein interactions. It is suggested that large
      protein complexes and aggregation seeds can unfold target proteins by virtue of
      their effect on the dielectric properties of water at the protein-solvent
      interface. Here, similar to the effect of membrane surfaces, protein surface can
      cause decrease in the local dielectric constant of solvent and thereby induce
      structural changes in a target protein approaching this surface. Some potential
      implementations of this hypothetical mechanism are also discussed.

PMID- 28516022
TI  - A NAD(P) reductase like protein is the salicylic acid receptor in the appendix of
      the Sauromatum guttatum inflorescence.
AB  - The mode of action of the thermogenic inducers (salicylic acid, aspirin, and 2,6
      dihydroxybenzoic acid) in the appendix of the Sauromatum guttatum inflorescence
      is poorly understood. Using ESI-MS and light scattering analysis, we have
      demonstrated that NAD(P) reductase like protein (RL) is the salicylic acid
      receptor in the Sauromatum appendix. RL was self-assembled in water into a large
      unit with a hydrodynamic diameter of 800 nm. In the presence of 1 pM salicylic
      acid, RL exhibited discontinuous and reversible volume phase transitions. The
      volume phase changed from 800 to 300 nm diameter and vice versa. RL stayed at
      each volume phase for ~4-5 min with a fast relaxation time between the 2 phases.
      ESI-MS analysis of RL extracted from appendices treated with salicylic acid,
      aspirin, and 2,6-DHBA at a micromolar range demonstrated that these compounds are
      capable of inducing graded conformational changes that are concentration
      dependent. A strong correlation between RL conformations and heat-production
      induced by salicylic acid was also observed. These preliminary findings reveal
      structural and conformational roles for RL by which plants regulate their
      temperature and synchronize their time keeping mechanisms.

PMID- 28516021
TI  - Multiple fuzzy interactions in the moonlighting function of thymosin-beta4.
AB  - Thymosine beta4 (Tbeta4) is a 43 amino acid long intrinsically disordered protein
      (IDP), which was initially identified as an actin-binding and sequestering
      molecule. Later it was described to have multiple other functions, such as
      regulation of endothelial cell differentiation, blood vessel formation, wound
      repair, cardiac cell migration, and survival.1 The various functions of Tbeta4
      are mediated by interactions with distinct and structurally unrelated partners,
      such as PINCH, ILK, and stabilin-2, besides the originally identified G-actin.
      Although the cellular readout of these interactions and the formation of these
      complexes have been thoroughly described, no attempt was made to study these
      interactions in detail, and to elucidate the thermodynamic, kinetic, and
      structural underpinning of this range of moonlighting functions. Because Tbeta4
      is mostly disordered, and its 4 described partners are structurally unrelated
      (the CTD of stabilin-2 is actually fully disordered), it occurred to us that this
      system might be ideal to characterize the structural adaptability and ensuing
      moonlighting functions of IDPs. Unexpectedly, we found that Tbeta4 engages in
      multiple weak, transient, and fuzzy interactions, i.e., it is capable of
      mediating distinct yet specific interactions without adapting stable folded
      structures.

PMID- 28516024
TI  - Disorder in the lifetime of a protein.
AB  - Intrinsic disorder is everywhere and is inevitable. The non-folding propensity is
      inherent for numerous natural polypeptide chains, and many functional proteins
      and protein regions are intrinsically disordered. Furthermore, at particular
      moments in their life, most notably during their synthesis and degradation, all
      ordered proteins are at least partially unfolded (disordered). Also, there is a
      widely spread phenomenon of conditional (functional or transient) disorder, where
      functions of many ordered proteins require local or even global unfolding of
      their unique structures. Finally, extrinsic disorder (i.e., intrinsic disorder in
      functional partners of ordered proteins) should be taken into account too.
      Therefore, even if a protein is completely devoid of intrinsically disordered
      regions in its mature form (which is a rather exceptional situation), it faces
      different forms of disorder (intrinsic, extrinsic, or induced disorder) at all
      the stages of its functional life, from birth to death. The goal of this article
      is to briefly introduce this concept of disorder in the lifetime of a protein.

PMID- 28516023
TI  - Transient disorder: Calcineurin as an example.
AB  - How intrinsically disordered proteins and regions evade degradation by cellular
      machinery evolved to recognize unfolded and misfolded chains remains a vexing
      question. One potential means by which this can occur is the disorder is
      transient in nature. That is, the disorder exists just long enough for it to be
      bound by a partner biomolecule and fold. A review of 30 y of studies of
      calmodulin's activation of calcineurin suggests that the regulatory domain of
      this vital phosphatase is a transiently disordered region. During activation, the
      regulatory domain progresses from a folded state, to disordered, followed by
      folding upon being bound by calmodulin. The transient disordered state of this
      domain is part of a critical intermediate state that facilitates the rapid
      binding of calmodulin. Building upon "fly-casting" as a means of facilitating
      partner binding, the mechanism by which calcineurin undergoes activation and
      subsequent deactivation could be considered "catch and release."

PMID- 28516027
TI  - Evolutionary journey of the Gc protein (vitamin D-binding protein) across
      vertebrates.
AB  - With so many diverse functions such as transporter of vitamin D metabolites and
      fatty acids, actin scavenger and macrophage activating factor, Gc must have been
      one of the most conserved proteins in animal kingdom. Our objective was to
      investigate the evolution of Gc by analyzing its differences at protein level.
      Using BLAST (Basic Local Alignment Search Tool) searches, Gc amino acid sequences
      were analyzed for homology. Clustal W2 and Jalview were used for multiple
      sequence alignment analysis, phylogenetic tree by PhyML 3.0 while Batch Web CD
      Search Tool was used for identification for conserved domains within protein
      sequences. Gc protein percent identity between human and rabbit was 83%, which
      decreased to 81% with cow, 78% with mouse, 76% with rat, 51% with chicken, 41%
      with frog and 28% with zebrafish. Phylogram showed that rat Gc was the most
      diverged, while chicken Gc was the most conserved protein. Analysis also
      indicated high homology among mammals (human, rabbit, cow, rat, and mouse). Gc is
      a highly conserved protein in chicken and zebrafish. However, the distance from
      ancestral protein gradually increased in amphibian (frog) and mammals (human,
      rabbit, cow, rat, and mouse). Human Gc and rabbit Gc appear to be recently
      evolved proteins. There appears to be an interesting evolutionary pattern-
      chicken Gc has the least distance from the ancestral protein, while rat Gc is the
      most diverged. There is no vertebrate devoid of Gc which is suggestive of its
      important role in vitamin D metabolism in vertebrates.

PMID- 28516026
TI  - Strain phenomenon in protein aggregation: Interplay between sequence and
      conformation.
AB  - Studies of yeast and mammalian prions introduced the idea that the protein
      aggregates can exist in multiple stable conformations that can be propagated by
      seeding. These conformational states (aka strains) were shown to have distinct
      physical (secondary structure, stability) and biological (cytotoxicity,
      infectivity) properties. For mammalian prions they were also tied to differences
      in disease pathology and incubation time. It was later shown that this phenomenon
      is not limited to prion proteins, and distinct conformational states of amyloid
      fibrils and oligomers derived from a variety of proteins can be propagated both
      in vitro and in vivo. Moreover, in some cases these conformations were preserved
      even when propagated into a protein with a different sequence. There is now an
      increasing body of evidence that strain phenomenon is a generic feature of
      protein aggregation, and characteristic features of amyloid strains can be
      transmitted between unrelated sequences.

PMID- 28516025
TI  - Designing disorder: Tales of the unexpected tails.
AB  - Protein tags of various sizes and shapes catalyze progress in biosciences. Well
      folded tags can serve to solubilize proteins. Small, unfolded, peptide-like tags
      have become invaluable tools for protein purification as well as protein-protein
      interaction studies. Intrinsically Disordered Proteins (IDPs), which lack unique
      3D structures, received exponentially increasing attention during the last
      decade. Recently, large ID tags have been developed to solubilize proteins and to
      engineer the pharmacological properties of protein and peptide pharmaceuticals.
      Here, we contrast the complementary benefits and applications of both folded and
      ID tags based on predictions of ID. Less structure often means more function in a
      shorter tag.

PMID- 28516029
TI  - The power of vertical geolocation of atmospheric profiles from GNSS radio
      occultation.
AB  - High-resolution measurements from Global Navigation Satellite System (GNSS) radio
      occultation (RO) provide atmospheric profiles with independent information on
      altitude and pressure. This unique property is of crucial advantage when
      analyzing atmospheric characteristics that require joint knowledge of altitude
      and pressure or other thermodynamic atmospheric variables. Here we introduce and
      demonstrate the utility of this independent information from RO and discuss the
      computation, uncertainty, and use of RO atmospheric profiles on isohypsic
      coordinates-mean sea level altitude and geopotential height-as well as on
      thermodynamic coordinates (pressure and potential temperature). Using
      geopotential height as vertical grid, we give information on errors of RO-derived
      temperature, pressure, and potential temperature profiles and provide an
      empirical error model which accounts for seasonal and latitudinal variations. The
      observational uncertainty of individual temperature/pressure/potential
      temperature profiles is about 0.7 K/0.15%/1.4 K in the tropopause region. It
      gradually increases into the stratosphere and decreases toward the lower
      troposphere. This decrease is due to the increasing influence of background
      information. The total climatological error of mean atmospheric fields is, in
      general, dominated by the systematic error component. We use sampling error
      corrected climatological fields to demonstrate the power of having different and
      accurate vertical coordinates available. As examples we analyze characteristics
      of the location of the tropopause for geopotential height, pressure, and
      potential temperature coordinates as well as seasonal variations of the
      midlatitude jet stream core. This highlights the broad applicability of RO and
      the utility of its versatile vertical geolocation for investigating the vertical
      structure of the troposphere and stratosphere.

PMID- 28516030
TI  - An Algorithm to detect balancing of iterated line sigraph.
AB  - A signedgraph (or sigraph in short) S is a graph G in which each edge x carries a
      value [Formula: see text] called its sign   denoted specially as [Formula: see
      text]. Given a sigraph S,  H = L(S)   called the line sigraph of S is that
      sigraph in which edges of S are represented as vertices, two of these vertices
      are defined to be adjacent whenever the corresponding edges in S have a vertex in
      common and any such edge ef is defined to be negative whenever both e and f are
      negative edges in S. Here S is called root sigraph of H. Iterated signed line
      graphs [Formula: see text] = [Formula: see text] k [Formula: see text] [Formula:
      see text], S:= [Formula: see text] is defined similarly. In this paper, we give
      an algorithm to obtain iterated line sigraph and detect for which value of 'k' it
      is balanced and determine its complexity. In the end we will propose a technique
      that will use adjacency matrix of S and adjacency matrix of [Formula: see text]
      which is balanced for some 'k' as a parameter to encrypt a network and forward
      the data in the form of balanced [Formula: see text] and will decrypt it by
      applying inverse matrix operations.

PMID- 28516031
TI  - Identifying appropriate protected areas for endangered fern species under climate
      change.
AB  - The management of protected areas (PAs) is widely used in the conservation of
      endangered plant species under climate change. However, studies that have
      identified appropriate PAs for endangered fern species are rare. To address this
      gap, we must develop a workflow to plan appropriate PAs for endangered fern
      species that will be further impacted by climate change. Here, we used endangered
      fern species in China as a case study, and we applied conservation planning
      software coupled with endangered fern species distribution data and distribution
      modeling to plan conservation areas with high priority protection needs under
      climate change. We identified appropriate PAs for endangered fern species under
      climate change based on the IUCN protected area categories (from Ia to VI) and
      planned additional PAs for endangered fern species. The high priority regions for
      protecting the endangered fern species were distributed throughout southern
      China. With decreasing temperature seasonality, the priority ranking of all
      endangered fern species is projected to increase in existing PAs. Accordingly, we
      need to establish conservation areas with low climate vulnerability in existing
      PAs and expand the conservation areas for endangered fern species in the high
      priority conservation regions.

PMID- 28516032
TI  - A case of respiratory infection possibly caused by Mycobacterium triviale:
      Current problems on diagnostic and therapeutic strategies.
AB  - Mycobacterium triviale is a subspecies of the Mycobacterium terrae complex, which
      rarely causes disease in humans. We encountered a case of respiratory infection,
      possibly caused by M. triviale, which was successfully treated by levofloxacin
      and clarithromycin. Although DNA-DNA hybridization identified M. triviale in one
      of three samples, clinical validations convinced us that it was the pathogen. 16s
      ribosomal RNA sequencing would have been reliable and ideal to perform in this
      case, although it is not covered by the insurance system in Japan. Nevertheless,
      this experience remains to be instructive because the clinical course, guidelines
      on the diagnosis, and therapeutic strategies for respiratory infections caused by
      M. triviale are not well-known or have not been established. Awareness of the
      possibility of respiratory infections caused by M. triviale and further
      collection and analysis of its predisposing conditions are essential.

PMID- 28516028
TI  - Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013).
AB  - The current literature on intrinsically disordered proteins is overwhelming. To
      keep interested readers up to speed with this literature, we continue a "Digested
      Disorder" project and represent a series of reader's digest type articles
      objectively representing the research papers and reviews on intrinsically
      disordered proteins. The only 2 criteria for inclusion in this digest are the
      publication date (a paper should be published within the covered time frame) and
      topic (a paper should be dedicated to any aspect of protein intrinsic disorder).
      The current digest issue covers papers published during the period of April, May,
      and June of 2013. The papers are grouped hierarchically by topics they cover, and
      for each of the included paper a short description is given on its major
      findings.

PMID- 28516034
TI  - Synergistic but independent: The role of corticospinal and alternate motor fibers
      for residual motor output after stroke.
AB  - BACKGROUND: Brain imaging has shown that not only the cortico-spinal tract (CST),
      but also alternate corticofugal motor fibers (aMF), such as the cortico-rubro
      spinal and cortico-reticulo-spinal tract, influence residual motor output after
      stroke. So far, studies mainly have investigated each tract separately. A
      combined analysis of CST and aMF with assessment of their interactive role, i.e.,
      that structural integrity of one tract influences the functional role of the
      structural integrity of the other, is pending. METHODS: 39 late subacute stroke
      patients (aged 59.4 +/- 12.0 years, 100 +/- 11 days after stroke) were included.
      Probabilistic tractography was used to reconstruct CST and aMF. Fractional
      anisotropy (FA) was calculated as a measure of microstructural integrity.
      Multiple-linear-regression analysis was used to associate tract-related FA with
      residual motor output and to determine interactions between CST and aMF. RESULTS:
      Both CST (coefficient = 3.93, p < 0.0001) and aMF (coefficient = - 4.43, p =
      0.003) of the affected hemisphere significantly contributed to residual motor
      output. An interaction of their impacts with a consecutive influence on motor
      output was not detected (p = 0.882). Thus, these data suggest that aMF and CST
      explain residual motor output in stroke patients in a synergistic, but mainly
      independent manner. CONCLUSIONS: The structural states of the CST and also - to a
      smaller degree - of the aMF correlate with residual motor output in late subacute
      stroke patients. Based on this statistical modeling with all inherent
      limitations, the novel finding of an absence of a significant interaction between
      both tracts in regard of their functional role, suggests that both corticofugal
      pathways act synergistically but largely independently. These findings add to the
      understanding of the functional role of different corticofugal motor fibers and
      their interactions for motor output after stroke.

PMID- 28516035
TI  - DNA shotgun sequencing analysis of Garcinia mangostana L. variety Mesta.
AB  - Mangosteen (Garcinia mangostana Linn.) is an ultra-tropical tree characterized by
      its unique dark purple fruits with white flesh. The xanthone-rich purple pericarp
      tissue contains valuable compounds with medicinal properties. Following
      previously reported genome sequencing of a common variety of mangosteen [1], we
      performed another whole genome sequencing of a commercially popular variety of
      this fruit species (var. Mesta) for comparative analysis of its genome
      composition. Raw reads of the DNA sequencing project were deposited to SRA
      database with the accession number SRX2709728.

PMID- 28516036
TI  - Transcriptome analysis of Carica papaya embryogenic callus upon De-etiolated 1
      (DET1) gene suppression.
AB  - Papaya is considered to be one of the most nutritional fruits. It is rich in
      vitamins, carotenoids, flavonoids and other phytonutrient which function as
      antioxidant in our body [1]. Previous studies revealed that the suppression of a
      negative regulator gene in photomorphogenesis, De-etiolated 1 (DET1) can improve
      the phytonutrient in tomato and canola without affecting the fruit quality [2],
      [3]. This report contains the experimental data on high-throughput 3' mRNA
      sequencing of transformed papaya callus upon DET1 gene suppression.

PMID- 28516037
TI  - Zika virus infection in a newly married Greek couple.
AB  - Zika virus (ZIKV) is a member of the Flaviviridae family causing asymptomatic or
      mildly symptomatic infections with fever, rash, arthralgia and headache. It is
      transmitted by the Aedes species mosquitoes and also sexually and
      transplacentally, and has been recently associated with congenital neurologic
      birth defects in South and Central America. We report the case of a newly married
      couple from Greece who travelled to Cuba for their honeymoon and developed mild
      symptoms consistent with arboviral infection. After returning to Greece, they
      were found to have been infected by Zika virus during their honeymoon. These are
      the first two cases of Zika virus infection in Greece, the southeastern border of
      Europe, denoting that Zika virus infection poses a threat for public health
      worldwide, since returning travelers could be asymptomatic carriers of the virus,
      not only leading to risk of neurologic birth defects for their offspring but also
      the real risk of transmission of the virus in their country by local Aedes
      mosquitoes.

PMID- 28516033
TI  - The impact of large structural brain changes in chronic stroke patients on the
      electric field caused by transcranial brain stimulation.
AB  - Transcranial magnetic stimulation (TMS) and transcranial direct current
      stimulation (TDCS) are two types of non-invasive transcranial brain stimulation
      (TBS). They are useful tools for stroke research and may be potential adjunct
      therapies for functional recovery. However, stroke often causes large cerebral
      lesions, which are commonly accompanied by a secondary enlargement of the
      ventricles and atrophy. These structural alterations substantially change the
      conductivity distribution inside the head, which may have potentially important
      consequences for both brain stimulation methods. We therefore aimed to
      characterize the impact of these changes on the spatial distribution of the
      electric field generated by both TBS methods. In addition to confirming the
      safety of TBS in the presence of large stroke-related structural changes, our aim
      was to clarify whether targeted stimulation is still possible. Realistic head
      models containing large cortical and subcortical stroke lesions in the right
      parietal cortex were created using MR images of two patients. For TMS, the
      electric field of a double coil was simulated using the finite-element method.
      Systematic variations of the coil position relative to the lesion were tested.
      For TDCS, the finite-element method was used to simulate a standard approach with
      two electrode pads, and the position of one electrode was systematically varied.
      For both TMS and TDCS, the lesion caused electric field "hot spots" in the
      cortex. However, these maxima were not substantially stronger than those seen in
      a healthy control. The electric field pattern induced by TMS was not
      substantially changed by the lesions. However, the average field strength
      generated by TDCS was substantially decreased. This effect occurred for both head
      models and even when both electrodes were distant to the lesion, caused by
      increased current shunting through the lesion and enlarged ventricles. Judging
      from the similar peak field strengths compared to the healthy control, both TBS
      methods are safe in patients with large brain lesions (in practice, however,
      additional factors such as potentially lowered thresholds for seizure-induction
      have to be considered). Focused stimulation by TMS seems to be possible, but
      standard tDCS protocols appear to be less efficient than they are in healthy
      subjects, strongly suggesting that tDCS studies in this population might benefit
      from individualized treatment planning based on realistic field calculations.

PMID- 28516039
TI  - A plane screw fixation is a nidus for Paecilomyces sinusitis in a patient with
      aspirin exacerbated respiratory disease.
AB  - Titanium plane screw fixation of the frontal sinus is an approach used by
      otolaryngologists to obliterate this space in an attempt to reduce sinus
      infections. In this case, however, the titanium used became a nidus of infection
      which cultured the fungus Paecilomyces. The patient also had a hypersensitivity
      reaction to mold with positive skin tests and IgE, as well as eosinophilic
      esophagitis. Treatment entailed anti-fungals, anti-IgE, and fungal immunotherapy
      to multiple fungal antigens prevalent to the geographic region. The patient also
      had aspirin exacerbated respiratory disease which responded to aspirin
      desensitization. Her symptoms resolved after 3 months.

PMID- 28516040
TI  - A newborn case with carnitine palmitoyltransferase II deficiency initially judged
      as unaffected by acylcarnitine analysis soon after birth.
AB  - Carnitine palmitoyltransferase II (CPT-2) deficiency, an autosomal recessive
      disorder of fatty acid oxidation, can be detected by newborn screening using
      tandem mass spectrometry (TMS). Our case was a boy born at 38 weeks and 6 days of
      gestation via normal vaginal delivery; his elder sister was affected with CPT-2
      deficiency. Acylcarnitine (AC) was analyzed in both dried blood spots (DBS) and
      serum 2 h after birth to determine whether the boy was also affected. His C16 and
      C18:1 AC levels in DBS were in the normal range, while his serum long-chain AC
      levels were marginally increased but lower than those of his sister. After the
      samples were taken, he was treated with glucose infusion to prevent any
      catabolism for 2 days. On day 4, the long-chain AC levels in both DBS and serum
      obtained were higher than those on day 0 and were equivalent to those of his
      sister. Genetic testing confirmed the presence of the same mutation found in his
      sister, a homozygous F383Y mutation in the CPT2 gene, thus leading to the
      diagnosis of CPT-2 deficiency. The sample for TMS should be taken between days 1
      and 7. If the sample is not obtained at an appropriate time, correct diagnosis
      may not be made, as in our case. Although early diagnosis is required, samples
      taken within 24 h after birth should not be used for TMS.

PMID- 28516038
TI  - Detection of Fusobacterium nucleatum in culture-negative brain abscess by broad
      spectrum bacterial 16S rRNA Gene PCR.
AB  - BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism commensal
      to the human oropharynx and gastrointestinal tract, which causes a wide spectrum
      of human diseases and it is an important pathogen in abscesses. CASE
      PRESENTATION: We report the case of a previously healthy 64-year-old woman with
      multiple abscesses due to Fusobacterium nucleatum, involving liver, pleura and
      brain. Fusobacterium was not recovered from blood cultures nor from culture of
      hepatic, pleural and brain drain fluid. The diagnosis was obtained by polymerase
      chain reaction amplification of bacterial deoxyribonucleic acid in brain abscess
      drain. CONCLUSIONS: Fusobacterium spp., should be considered in patients with any
      organ abscess, especially in case of invasive disease with multiple secondary
      site involving brain. MOLECULAR: techniques might be of special usefulness in
      cases that remain negative in culture to obtain the diagnosis and perform
      adequate treatment.

PMID- 28516041
TI  - Birth weight in patients with mucopolysaccharidosis type II: Data from the Hunter
      Outcome Survey (HOS).
AB  - There is a need to identify early disease markers to facilitate diagnosis of
      mucopolysaccharidosis type II (MPS II; Hunter syndrome). Mean birth weight and
      its association with disease severity was investigated in 609 patients enrolled
      in the Hunter Outcome Survey (HOS). This analysis indicated that birth weight is
      not an early marker of MPS II and is not associated with disease severity. It
      remains important to investigate the utility of other factors for early/pre
      symptomatic diagnosis.

PMID- 28516042
TI  - Sensitivity enhancement of traveling wave MRI using free local resonators: an
      experimental demonstration.
AB  - BACKGROUND: Traveling wave MR uses the far fields in signal excitation and
      reception, therefore its acquisition efficiency is low in contrast to the
      conventional near field magnetic resonance (MR). Here we show a simple and
      efficient method based on the local resonator to improving sensitivity of
      traveling wave MR technique. The proposed method utilizes a standalone or free
      local resonator to amplify the radio frequency magnetic fields in the interested
      target. The resonators have no wire connections to the MR system and thus can be
      conveniently placed to any place around imaging simples. METHODS: A rectangular
      loop L/C resonator to be used as the free local resonator was tuned to the proton
      Larmor frequency at 7T. Traveling wave MR experiments with and without the
      wireless free local resonator were performed on a living rat using a 7T whole
      body MR scanner. The signal-to-noise ratio (SNR) or sensitivity of the images
      acquired was compared and evaluated. RESULTS: In vivo 7T imaging results show
      that traveling wave MR with a wireless free local resonator placed near the head
      of a living rat achieves at least 10-fold SNR gain over the images acquired on
      the same rat using conventional traveling wave MR method, i.e. imaging with no
      free local resonators. CONCLUSIONS: The proposed free local resonator technique
      is able to enhance the MR sensitivity and acquisition efficiency of traveling
      wave MR at ultrahigh fields in vivo. This method can be a simple solution to
      alleviating low sensitivity problem of traveling wave MRI.

PMID- 28516043
TI  - Quantification of regional deformation of the lungs by non-rigid registration of
      three-dimensional contrast-enhanced magnetic resonance imaging.
AB  - BACKGROUND: Assessment of lung function is vital for the diagnosis of a variety
      of pathological conditions. Research has been proposed to study pulmonary
      mechanics and kinematics using two-dimensional (2D) magnetic resonance imaging
      (MRI). This allows estimation of regional lung tissue mechanics but is limited to
      2D information. An approach based on three-dimensional (3D) contrast-enhanced MR
      angiogram of pulmonary blood vessels and a non-rigid image registration technique
      is proposed for quantification of lung regional deformations, which can
      potentially be used for assessment of pulmonary parenchymal mechanics and
      regional ventilation for disease diagnosis without ionizing radiation. METHODS:
      On three volunteers, an end-expiration scan and end-inspiration scan was acquired
      successively for each volunteer using a 3D breath-hold contrast-enhanced MRI
      sequence several minutes after gadolinium injection. Subsequently, a rectangle
      box lung mask is manually selected for each end-expiration scan, applying non
      rigid registration algorithms using cubic B-splines as transformations to align
      each pair of images. This incorporates the Normalized Correlation Coefficient
      similarity with the bending energy term as cost function with a multi-resolution
      multi-grid approach. Finally, the lung regional 3D deformations were obtained
      using the transformations obtained by registration. The alignment accuracy after
      non-rigid registration was estimated by using a set of branch points of pulmonary
      blood vessels as anatomical landmarks for each pair of images. RESULTS: With
      contrast enhancement, the pulmonary blood vessel signal was enhanced, which
      greatly facilitated the non-rigid registration in the lung parenchyma. The
      average landmarks distances in three pairs of datasets are reduced from 17.9,
      20.3 and 16.3 mm, to 1.0, 1.6 and 1.2 mm, respectively, by non-rigid
      registration. After registration, the average distances error of each pair of
      datasets was less than 0.6 mm in the right-to-left (RL) direction, less than 0.9
      mm in the inferior-to-superior (IS) direction, and less than 1.2 mm in the
      anterior-to-posterior (AP) direction. CONCLUSIONS: Results demonstrated that the
      proposed method can accurately register lungs with large deformations to evaluate
      lung regional deformation. It may be used for quantitative assessment of 3D lung
      regional ventilation avoiding ionizing radiation.

PMID- 28516044
TI  - Design of catheter radio frequency coils using coaxial transmission line
      resonators for interventional neurovascular MR imaging.
AB  - BACKGROUND: It is technically challenging to design compact yet sensitive
      miniature catheter radio frequency (RF) coils for endovascular interventional MR
      imaging. METHODS: In this work, a new design method for catheter RF coils is
      proposed based on the coaxial transmission line resonator (TLR) technique. Due to
      its distributed circuit, the TLR catheter coil does not need any lumped
      capacitors to support its resonance, which simplifies the practical design and
      construction and provides a straightforward technique for designing miniature
      catheter-mounted imaging coils that are appropriate for interventional
      neurovascular procedures. The outer conductor of the TLR serves as an RF shield,
      which prevents electromagnetic energy loss, and improves coil Q factors. It also
      minimizes interaction with surrounding tissues and signal losses along the
      catheter coil. To investigate the technique, a prototype catheter coil was built
      using the proposed coaxial TLR technique and evaluated with standard RF testing
      and measurement methods and MR imaging experiments. Numerical simulation was
      carried out to assess the RF electromagnetic field behavior of the proposed TLR
      catheter coil and the conventional lumped-element catheter coil. RESULTS: The
      proposed TLR catheter coil was successfully tuned to 64 MHz for proton imaging at
      1.5 T. B1 fields were numerically calculated, showing improved magnetic field
      intensity of the TLR catheter coil over the conventional lumped-element catheter
      coil. MR images were acquired from a dedicated vascular phantom using the TLR
      catheter coil and also the system body coil. The TLR catheter coil is able to
      provide a significant signal-to-noise ratio (SNR) increase (a factor of 200 to
      300) over its imaging volume relative to the body coil. CONCLUSIONS: Catheter
      imaging RF coil design using the proposed coaxial TLR technique is feasible and
      advantageous in endovascular interventional MR imaging applications.

PMID- 28516045
TI  - Exploration of highly accelerated magnetic resonance elastography using high
      density array coils.
AB  - BACKGROUND: Magnetic resonance elastography (MRE) measures tissue mechanical
      properties by applying a shear wave and capturing its propagation using magnetic
      resonance imaging (MRI). By using high density array coils, MRE images are
      acquired using single echo acquisition (SEA) and at high resolutions with
      significantly reduced scan times. METHODS: Sixty-four channel uniplanar and 32*32
      channel biplanar receive arrays are used to acquire MRE wave image sets from agar
      samples containing regions of varying stiffness. A mechanical actuator triggered
      by a stepped delay time introduces vibrations into the sample while a motion
      sensitizing gradient encodes micrometer displacements into the phase. SEA imaging
      is used to acquire each temporal offset in a single echo, while multiple echoes
      from the same array are employed for highly accelerated imaging at high
      resolutions. Additionally, stiffness variations as a function of temperature are
      studied by using a localized heat source above the sample. A custom insertable
      gradient coil is employed for phase compensation of SEA imaging with the biplanar
      array to allow imaging of multiple slices. RESULTS: SEA MRE images show a
      mechanical shear wave propagating into and across agar samples. A set of 720
      images was obtained in 720 echoes, plus a single reference scan for both harmonic
      and transient MRE. A set of 2,950 wave image frames was acquired from pairs of
      SEA images captured during heating, showing the change in mechanical wavelength
      with the change in agar properties. A set of 240 frames was acquired from two
      slices simultaneously using the biplanar array, with phase images processed into
      displacement maps. Combining the narrow sensitivity patterns and SNR advantage of
      the SEA array coil geometry allowed acquisition of a data set with a resolution
      of 156 um * 125 um * 1,000 um in only 64 echoes, demonstrating high resolution
      and high acceleration factors. CONCLUSIONS: MRE using high-density arrays offers
      the unique ability to acquire a single frame of a propagating mechanical
      vibration with each echo, which may be helpful in non-repeatable or destructive
      testing. Highly accelerated, high resolution MRE may be enabled by the use of
      large arrays of coils such as used for SEA, but at lower acceleration rates
      supporting the higher resolution than provided by SEA imaging.

PMID- 28516046
TI  - Image quality assessment of a 1.5T dedicated magnetic resonance-simulator for
      radiotherapy with a flexible radio frequency coil setting using the standard
      American College of Radiology magnetic resonance imaging phantom test.
AB  - BACKGROUND: A flexible RF coil setting has to be used on an MR-simulator (MR-sim)
      in the head and neck simulation scan for radiotherapy (RT) purpose, while the
      image quality might be compromised due to the sub-optimized flexible coil
      compared to the normal diagnostic radiological (DR) head coil. In this study, we
      assessed the image quality of an MR-sim by conducting the standard American
      College of Radiology (ACR) MRI phantom test on a 1.5T MR-sim under RT-setting and
      comparing it to DR-setting. METHODS: A large ACR MRI phantom was carefully
      positioned, aligned and scanned 9 times for each under RT- and DR-setting on a
      1.5T MR-sim, following the ACR scanning instruction. Images were analyzed
      following the ACR guidance. Measurement results under two coil settings were
      quantitatively compared. Inter-observer disagreements under RT-setting between
      two physicists were compared using Bland-Altman (BA) analysis and intra-class
      correlation coefficient (ICC). RESULTS: The MR-sim with RT-setting obtained
      sufficiently good image quality to pass all ACR recommended criteria. No
      significant difference was found in phantom length accuracy, high-contrast
      spatial resolution, slice thickness accuracy, slice position accuracy, and
      percent-signal ghosting. RT-setting significantly under-performed in low-contrast
      object detectability, while better performed in image intensity uniformity. BA
      analysis showed that 95% limit of agreement and biases of phantom test
      measurement under RT-setting between two observers were very small. Excellent
      inter-observer agreement (ICC >0.75) was achieved in all measurements except for
      slice thickness accuracy (ICC =0.42, moderate agreement) under RT-setting.
      CONCLUSIONS: Very good and highly reproducible image quality could be achieved on
      a 1.5T MR-sim with a flexible coil setting as revealed by the standard ACR MRI
      phantom test. The flexible RT-setting compromised in image signal-to-noise ratio
      (SNR) compared to the normal DR-setting, and resulted in reduced low-contrast
      object detectability.

PMID- 28516047
TI  - Prospective cardiac motion self-gating.
AB  - BACKGROUND: To develop a prospective cardiac motion self-gating method that
      provides robust and accurate cardiac triggers in real time. METHODS: The proposed
      self-gating method consists of an "imaging mode" that acquires the k-space
      segments and a "self-gating mode" that captures the cardiac motion by repeatedly
      sampling the k-space centerline. A training based principal component analysis
      algorithm is utilized to process the self-gating data where the projection onto
      the first principal component was used as the self-gating signal. Retrospective
      studies using a sequence with self-gating mode only was performed on 8 healthy
      subjects to validate the accuracy and reliability of the self-gating triggers.
      Prospective studies using both ECG-gated and self-gated cardiac CINE sequences
      were conducted on 6 healthy subjects to compare the image quality. RESULTS: Using
      the ECG as the reference, the proposed method was able to detect self-gating
      triggers within +/-10 ms accuracy on all 8 subjects in the retrospective study.
      The prospectively self-gated CINE sequence successfully detected 100% of the
      cardiac triggers and provided excellent CINE image quality without using ECG
      signals. CONCLUSIONS: The proposed cardiac self-gating method is a robust and
      accurate alternative to conventional ECG-based gating method for a number of
      cardiac MRI applications.

PMID- 28516049
TI  - Analysis of phase error effects in multishot diffusion-prepared turbo spin echo
      imaging.
AB  - BACKGROUND: To characterize the effect of phase errors on the magnitude and the
      phase of the diffusion-weighted (DW) signal acquired with diffusion-prepared
      turbo spin echo (dprep-TSE) sequences. METHODS: Motion and eddy currents were
      identified as the main sources of phase errors. An analytical expression for the
      effect of phase errors on the acquired signal was derived and verified using
      Bloch simulations, phantom, and in vivo experiments. RESULTS: Simulations and
      experiments showed that phase errors during the diffusion preparation cause both
      magnitude and phase modulation on the acquired data. When motion-induced phase
      error (MiPe) is accounted for (e.g., with motion-compensated diffusion encoding),
      the signal magnitude modulation due to the leftover eddy-current-induced phase
      error cannot be eliminated by the conventional phase cycling and sum-of-squares
      (SOS) method. By employing magnitude stabilizers, the phase-error-induced
      magnitude modulation, regardless of its cause, was removed but the phase
      modulation remained. The in vivo comparison between pulsed gradient and flow
      compensated diffusion preparations showed that MiPe needed to be addressed in
      multi-shot dprep-TSE acquisitions employing magnitude stabilizers. CONCLUSIONS: A
      comprehensive analysis of phase errors in dprep-TSE sequences showed that
      magnitude stabilizers are mandatory in removing the phase error induced magnitude
      modulation. Additionally, when multi-shot dprep-TSE is employed the inconsistent
      signal phase modulation across shots has to be resolved before shot-combination
      is performed.

PMID- 28516048
TI  - Image interpolation improves the zonal analysis of cartilage T2 relaxation in
      MRI.
AB  - BACKGROUND: This project aimed to investigate the improvement in the detection of
      osteoarthritis (OA) in cartilage by the interpolation of T2 images, in the
      situation when the native MRI resolution is insufficient to resolve the depth
      dependent T2 characteristics in articular cartilage (AC). METHODS: Eighteen
      intact canine knee joints that were healthy or had mild (contralateral) or severe
      OA were T2-imaged in a 7T/20 cm MRI system at 200 um/pixel resolution (macro
      MRI). Two image analysis methods were used to interpolate the images to 100
      um/pixel, i.e., by Fourier-transforming the time-domain FID (Free Induction
      Decay) signal using the Varian NMR software and by interpolating the 2D T2 image
      using the ImageJ software. RESULTS: The T2 profiles from 30 individual ROI of
      each healthy [6], mild [6] and OA [6] cartilage at 200 um and the interpolated
      100 um resolutions were subdivided into two equal-thickness regions and three
      equal thickness regions based on clinical MRI protocols. A new method divided the
      T2 profiles into three-unequal thickness zones according to the T2 profiles at
      17.6 um/pixel from the same cartilage imaged in a 7 Tesla/9 cm uMRI system. Both
      interpolation methods improved the depth-dependent T2 images/profiles in macro
      MRI. The unequal zone division in T2 had better OA sensitivity than the equal
      zone division. The three-equal zone division of T2 profiles had better OA
      sensitivity than the two-equal zone division. The statistical significant
      difference between the healthy and mild OA cartilage is detected (P=0.0018) only
      by the unequal zone division method at 100 um resolution. CONCLUSIONS: Data
      interpolation improves the T2 sensitivity in MRI of cartilage OA. Unequal
      division of tissue thickness enables better early stage of OA detection than the
      equal division.

PMID- 28516050
TI  - Towards MRI temperature mapping in real time-the proton resonance frequency
      method with undersampled radial MRI and nonlinear inverse reconstruction.
AB  - BACKGROUND: Optimal control of minimally invasive interventions by hyperthermia
      requires dynamic temperature mapping at high temporal resolution. METHODS: Based
      on the temperature-dependent shift of the proton resonance frequency (PRF), this
      work developed a method for real-time MRI thermometry which relies on highly
      undersampled radial FLASH MRI sequences with iterative image reconstruction by
      regularized nonlinear inversion (NLINV). As a first step, the method was
      validated with use of a temperature phantom and ex vivo organs (swine kidney)
      subjected to heating by warm water or a pulsed laser source. RESULTS: The
      temperature maps obtained by real-time PRF MRI demonstrate good accuracy as
      independently controlled by fiber-optic temperature sensors. Moreover, the
      dynamic results demonstrate both excellent sensitivity to single laser pulses (20
      ms duration, 6 J energy output) and high temporal resolution, i.e., 200 ms
      acquisition times per temperature map corresponding to a rate of 5 frames per
      second. In addition, future extensions to in vivo applications were prepared by
      addressing the breathing-related motion problem by a pre-recorded library of
      reference images representative of all respiratory states. CONCLUSIONS: The
      proposed method for real-time MRI thermometry now warrants further developments
      towards in vivo MRI monitoring of thermal interventions in animals.

PMID- 28516051
TI  - Evaluation of MR thermometry with proton resonance frequency method at 7T.
AB  - Quantitative and non-invasive temperature mapping using magnetic resonance
      imaging (MRI) provides a unique way to measure temperature evolution inside
      biological tissues. The method is widely used in thermal ablation procedures with
      magnetic fields at or below 3T. In this paper, the sensitivity of the MRI
      thermometry at 7T was studied using a proton resonance frequency (PRF)-based
      technique. We first used an agarose gel phantom with MR-compatible thermometry to
      calibrate the temperature coefficient, and then this temperature coefficient was
      employed to measure the internal temperature in both ex vivo (beef muscle) and in
      vivo (rat) experiments using focused ultrasound heating. The temperature
      coefficient calibrated by the phantom was 0.0095 ppm/ degrees C, and both the ex
      vivo and in vivo experiments exhibited clear temperature evolution. This
      quantitative study confirmed the sensitivity (<1  degrees C) of MR temperature
      mapping at 7T.

PMID- 28516053
TI  - Implication of pulmonary-systemic flow information in the management of complex
      presentation of pulmonary arterial hypertension: exploring role of phase contrast
      MRI technique.

PMID- 28516054
TI  - Current trends in bone tissue regeneration.

PMID- 28516052
TI  - Whole body MRI of the non-human primate using a clinical 3T scanner: initial
      experiences.
AB  - With the advent of parallel imaging MRI techniques, whole-body MRI is being
      increasingly used in clinical diagnosis. However, its application in preclinical
      research using large animals remains very limited. In the present study, the
      whole-body MRI techniques for adult macaque monkeys were explored using a
      conventional clinic 3T scanner. The T1, T2 anatomical images, and MR angiography
      of adult macaque whole bodies were illustrated. The preliminary results suggest
      whole-body MRI can be a robust tool to examine multiple organs of non-human
      primate (NHP) models from head to toe non-invasively and simultaneously using a
      conventional clinical setting. As NHPs are intensely used in biomedical research
      such as HIV/AIDS and vaccine discovery, whole body MRI techniques can have a wide
      range of applications in translational research using NHPs.

PMID- 28516055
TI  - Antimicrobial and enzymatic activity of actinomycetes isolated from soils of
      coastal islands.
AB  - Microbiological investigation of unexplored ecosystems is crucial for discovering
      of antibiotic producing actinomycetes. The present study was conducted to
      determine antimicrobial activity and identify the most active strains.
      Actinomycetes were isolated using the spread plate technique following by serial
      dilution of samples on starch casein agar. The screening method consists of
      primary and secondary testing. The most active isolates were identified based on
      molecular and cultural methods. 42 out of 66 isolates displayed antimicrobial
      potential. 63% exhibited antibacterial activity, 16% antifungal activity, and 16%
      displayed both activities. Identified isolates, Streptomyces scabrisporus,
      Streptomyces sparsogenes, Streptomyces misakiensis, Streptomyces cirratus,
      Streptomyces lincolnensis, Streptomyces endophyticus, Streptomyces chartreusis,
      and Streptomyces alboniger showed a broad spectrum of enzymatic activities. The
      results indicated that these isolates may serve as antibiotic and enzyme
      producing microbes.

PMID- 28516056
TI  - Simultaneous micronization and purification of bioactive fraction by
      supercritical antisolvent technology.
AB  - Simultaneous micronization and purification of DLBS3233 bioactive fraction, a
      combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum
      burmannii has been successfully performed via supercritical anti-solvent (SAS)
      technology. The objective of the present study was to investigate the
      effectiveness of SAS technology to micronize and reduce coumarin content of
      DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature,
      concentration and solution flow rate on particle formation were investigated. In
      SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid
      solvent. The solution was then pumped through a nozzle into a chamber
      simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti
      solvent, resulting in DLBS3233 precipitation. Physicochemical properties of
      unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using
      scanning electron microscopy (SEM) and high pressure liquid chromatography
      (HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean
      particle size ranging from 0.107+/-0.028 MUm to 0.298+/-0.138 MUm were obtained
      by varying the process parameters. SAS-processed DLBS3233 particles showed no
      coumarin content in all experiments studied in this work. Results of TPC analysis
      revealed no significant change in SAS-processed DLBS3233 particles compared to
      unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have
      been successfully produced using SAS process. This study demonstrates the ability
      of SAS for processing herbal medicine in single step process.

PMID- 28516057
TI  - Comparison of atracurium and methocarbamol for preventing succinylcholine-induced
      muscle fasciculation: A randomized controlled trial.
AB  - Fasciculation is a minor adverse effect of succinylcholine and may be an
      unpleasant experience for patient. The aim of this study was to compare the use
      of atracurium and methocarbamol to decrease the occurrence and severity of
      succinylcholine-induced muscle fasciculation. Fifty-nine adults with American
      Society of Anesthesiologists I or II hospitalized for elective surgery were
      randomly assigned to two groups: Group A (n = 29) who received succinylcholine 1
      mg/kg body weight (BW) intravenously followed by 0.2-0.5 mg/kg BW atracurium and
      patients in Group B (n= 29) who received succinylcholine 1 mg/kg BW intravenously
      followed by methocarbamol 0.2-0.5 mg/kg BW. Anesthesia was induced in all
      patients with thiopental sodium 3-5 mg/kg. Fasciculation was scored on a four
      point (0-4) Likert scale. There were no statistically significant differences in
      demographic variables between two groups, whereas in Group A, 27 patients (93.1%)
      suffered from mild fasciculation and two (6.9%) from moderate fasciculation. In
      Group B, twenty patients (68.9%) suffered from mild fasciculation, five (17.2%)
      from moderate fasciculation, and four (13.9%) from severe fasciculation. The
      difference between the groups was statistically significant (P < 0.05).
      Atracurium is more effective than methocarbamol in decreasing the occurrence and
      severity of succinylcholine-induced fasciculations. In addition, the use of
      methocarbamol before succinylcholine administration can decrease the incidence of
      severe fasciculation.

PMID- 28516058
TI  - Comparison of amoxicillin and metronidazole effect on three-drug regimen for the
      treatment of Helicobacter pylori infection in children.
AB  - Helicobacter pylori is an important risk factor for chronic gastritis, peptic
      ulcer, and gastric cancer. Three-drug regimen is the first-line treatment for
      this infection, but the response rate to treatment varies in different
      geographical regions. This study was conducted to comparatively determine the
      effect of amoxicillin and metronidazole on three-drug regimen to treat H. pylori
      infection in 1-15-year-old children. This clinical trial was conducted on 82
      patients aged 1-15 years with convenience sampling referring to the Endoscopy
      Unit of Hajar Hospital, Shahrekord. Group 1 was administered with clarithromycin,
      amoxicillin, and omeprazole (CAO), and Group 2 with, clarithromycin,
      metronidazole, and omeprazole (CMO). One month after completion of the treatment,
      stool antigen test was used to study the eradication of H. pylori. Data were
      analyzed using SPSS software by Chi-square test. Three of the 82 patients were
      excluded from the study because of side effects caused by drugs. Nearly 87.2% of
      the patients in CAO-treated group and 92.5% in CMO-treated group had response to
      treatment. There was no significant difference in eradication rate between the
      two regimens (P = 0.43). The two regimens displayed no superiority over each
      other for eradicating H. pylori infection and response rate to treatment in
      children aged 1-15 years.

PMID- 28516059
TI  - The effects of cognitive behavioral therapy and drug therapy on quality of life
      and symptoms of patients with irritable bowel syndrome.
AB  - Psychotherapy and drug therapy are considered useful in quality of life (QOL) and
      symptoms of patients with irritable bowel syndrome (IBS). The aim of this study
      was to examine the effects of cognitive behavioral therapy (CBT) associated with
      drug therapy in comparison to drug therapy alone on the QOL and symptoms of IBS
      patients with diarrhea predominance. This study was a randomized clinical trial
      on 64 IBS patients. The patients were selected according to Rome III criteria and
      were assigned into two groups. Bowel symptom severity and frequency scale and QOL
      IBS were used to investigate the patients' symptoms. The first group underwent
      CBT with medication therapy, and the second group received only medication. Data
      were analyzed using analysis of multiple covariance. The two groups showed a
      significant difference in the QOL-IBS in posttreatment and follow-up stages (P <
      0.05). There were significant differences in the severity and frequency of IBS
      symptoms between the two groups after the intervention (P < 0.05). However, no
      significant difference was observed at follow-up stage between the two groups (P
      > 0.05). CBT accompanied by drug therapy can be useful for IBS patients with
      diarrhea predominance. However, discontinuing this treatment may lead to
      recurrence of the symptoms.

PMID- 28516061
TI  - The effect of vaginal cream containing ginger in users of clotrimazole vaginal
      cream on vaginal candidiasis.
AB  - Vulvovaginal candidiasis is one of the most common infections of the genital
      tract in women that causes many complications. Therefore, we examined the
      clinical effect of ginger cream along with clotrimazole compared to vaginal
      clotrimazole alone in this study. This double-blind clinical trial was conducted
      on 67 women admitted to the Gynecology Clinic of Hajar Hospital with vaginal
      candidiasis. The patients were divided randomly into two groups of 33 and 34
      people. The diagnosis was made according to clinical symptoms, wet smear, and
      culture. Ginger-clotrimazole vaginal cream 1% and clotrimazole vaginal cream 1%
      were administered to groups 1 and 2, respectively, once a day for 7 days and
      therapeutic effects and symptoms were evaluated in readmission. Data analysis was
      performed using SPSS version 22, t-test and Chi-square. The mean value of
      variables itching (P > 0.05), burning (P > 0.05), and cheesy secretion (P < 0.05)
      in users of ginger-clotrimazole was less than the other group after the
      treatment. Recurrence in clotrimazole group was 48.5% and in ginger-clotrimazole
      group 51.2% during the 1-month follow-up with no significant difference. Study
      results showed that cream containing ginger and clotrimazole 1% was more
      effective and may be more useful than the clotrimazole to treat vaginal
      candidiasis.

PMID- 28516060
TI  - The effects of Vitamin C on sperm quality parameters in laboratory rats following
      long-term exposure to cyclophosphamide.
AB  - Cyclophosphamide is a widely used medication and can cause oxidative stress. This
      study was conducted to investigate the effects of Vitamin C on reproductive
      organs' weight and the quality of sperm parameters in laboratory rats. In this
      experimental study, 40 rats were randomly assigned into five groups of eight
      each. Distilled water (DW) group received only food and water, Group 2 was
      administered with drug solvent (DW) by gavage, Group 3 intraperitoneally
      administered with 1.6 mg/kg cyclophosphamide, Group 4 gavaged Vitamin C at 0.88
      mg/kg, and Group 5 administered with effective doses of Vitamin C and
      cyclophosphamide by gavage with 1-h intervals. Sperm parameters of the samples
      were taken from distal epididymis and tissues were studied, and the data were
      analyzed by SPSS version 22. The lowest weight of testicles and epididymis was
      seen in cyclophosphamide-exposed rats and the highest weight of testicles and
      epididymis in Vitamin C-exposed rats (P < 0.05). The highest motility,
      progression, viability, and count of sperm were seen in the Vitamin C-treated
      group and the lowest in the cyclophosphamide-exposed group. The highest
      proportion of sperm anomalies was seen in the cyclophosphamide-exposed group.
      Vitamin C, as an antioxidant, can be effective on some of the sperm parameters
      and can reduce cyclophosphamide-induced complications in animal model.

PMID- 28516062
TI  - Endoplasmic Reticulum-Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival.
AB  - Calcium ions (Ca2+) are crucial, ubiquitous, intracellular second messengers
      required for functional mitochondrial metabolism during uncontrolled
      proliferation of cancer cells. The mitochondria and the endoplasmic reticulum
      (ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER
      mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to
      several aspects of cellular survival, autophagy, metabolism, cell death
      sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted
      to these constitutive ER-mitochondrial Ca2+ fluxes for their survival, since they
      drive the tricarboxylic acid cycle and the production of mitochondrial substrates
      needed for nucleoside synthesis and proper cell cycle progression. In addition to
      this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to
      hypoxia-inducible factor 1alpha signaling, enabling metastasis and invasion
      processes, but they can also contribute to cellular senescence induced by
      oncogenes and replication. Finally, proper ER-mitochondrial Ca2+ transfer seems
      to be a key event in the cell death response of cancer cells exposed to
      chemotherapeutics. In this review, we discuss the emerging role of ER
      mitochondrial Ca2+ fluxes underlying these cancer-related features.

PMID- 28516063
TI  - Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the
      Endoplasmic Reticulum-Mitochondrial Interface.
AB  - Mitochondria are important regulators of cell death and cell survival.
      Mitochondrial Ca2+ levels are critically involved in both of these processes. On
      the one hand, excessive mitochondrial Ca2+ leads to Ca2+-induced mitochondrial
      outer membrane permeabilization and thus apoptosis. On the other hand,
      mitochondria need Ca2+ in order to efficiently fuel the tricarboxylic acid cycle
      and maintain adequate mitochondrial bioenergetics. For obtaining this Ca2+, the
      mitochondria are largely dependent on close contact sites with the endoplasmic
      reticulum (ER), the so-called mitochondria-associated ER membranes. There, the
      inositol 1,4,5-trisphosphate receptors are responsible for the Ca2+ release from
      the ER. It comes as no surprise that this Ca2+ release from the ER and the
      subsequent Ca2+ uptake at the mitochondria are finely regulated. Cancer cells
      often modulate ER-Ca2+ transfer to the mitochondria in order to promote cell
      survival and to inhibit cell death. Important regulators of these Ca2+ signals
      and the onset of cancer are the B-cell lymphoma 2 (Bcl-2) family of proteins. An
      increasing number of reports highlight the ability of these Bcl-2-protein family
      members to finely regulate Ca2+ transfer from ER to mitochondria both in healthy
      cells and in cancer. In this review, we focus on recent insights into the dynamic
      regulation of ER-mitochondrial Ca2+ fluxes by Bcl-2-family members and how this
      impacts cell survival, cell death and mitochondrial energy production.

PMID- 28516067
TI  - COGNITOMICS: a new approach for the evaluation of the relationship between
      diseases and cognition to be designed based on normal behavioral tendencies in
      real life, a conceptual framework.
AB  - The relationship between medical diseases and cognition has been a point of
      interest in the last decades. In recent years studies in this field have
      developed significantly applying various tools such as cognitive tests using
      psychometric assessments and brain imaging techniques. The main focus of
      cognitive function in this studies is the process through which this cognition is
      obtained. It seems a novel methodology is needed while assessing the impact of
      diseases such as diabetes on cognition based on heavenly religious teachings in
      which cognition is believed to be the main source of human bliss and not just
      some measurable quantitative components.

PMID- 28516064
TI  - A Novel Role of Listeria monocytogenes Membrane Vesicles in Inhibition of
      Autophagy and Cell Death.
AB  - Bacterial membrane vesicle (MV) production has been mainly studied in Gram
      negative species. In this study, we show that Listeria monocytogenes, a Gram
      positive pathogen that causes the food-borne illness listeriosis, produces MVs
      both in vitro and in vivo. We found that a major virulence factor, the pore
      forming hemolysin listeriolysin O (LLO), is tightly associated with the MVs,
      where it resides in an oxidized, inactive state. Previous studies have shown that
      LLO may induce cell death and autophagy. To monitor possible effects of LLO and
      MVs on autophagy, we performed assays for LC3 lipidation and LDH sequestration as
      well as analysis by confocal microscopy of HEK293 cells expressing GFP-LC3. The
      results revealed that MVs alone did not affect autophagy whereas they effectively
      abrogated autophagy induced by pure LLO or by another pore-forming toxin from
      Vibrio cholerae, VCC. Moreover, Listeria monocytogenes MVs significantly
      decreased Torin1-stimulated macroautophagy. In addition, MVs protected against
      necrosis of HEK293 cells caused by the lytic action of LLO. We explored the
      mechanisms of LLO-induced autophagy and cell death and demonstrated that the
      protective effect of MVs involves an inhibition of LLO-induced pore formation
      resulting in inhibition of autophagy and the lytic action on eukaryotic cells.
      Further, we determined that these MVs help bacteria to survive inside eukaryotic
      cells (mouse embryonic fibroblasts). Taken together, these findings suggest that
      intracellular release of MVs from L. monocytogenes may represent a bacterial
      strategy to survive inside host cells, by its control of LLO activity and by
      avoidance of destruction from the autophagy system during infection.

PMID- 28516065
TI  - miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating
      Encephalomyelitis Virus Infection by Targeting Ulk1.
AB  - Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central
      nervous system (CNS) and causes neurodegenerative disease in suckling piglets,
      but the understanding of its neuropathogenicity for neurological dysfunction
      remains limited. Here, we report that miR-142-5p is localized to neurons and
      negatively regulates neuronal morphogenesis in porcine hemagglutinating
      encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of
      an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and
      dendrite formation. Modulating miR-142-5p activity by microRNA mimics or
      inhibitors induced neurodegeneration, including stunted axon elongation, unstable
      dendritic spine formation, and irregular swelling and disconnection in neurites.
      Relieving Ulk1 mRNA repression in primary cortical neurons by miR-142-5p
      antagomirs or replication-deficient adenoviruses encoding Ulk1 (Ad5-Ulk1), which
      improved rescue of nerve injury, restricted viral replication, and increased
      survival rate in mice underlying PHEV infection. In contrast, disrupting Ulk1 in
      RNAi-expressing neurons mostly led to significantly shortened axon elongation
      and/or an abnormally large number of branched dendrites. Taken together, we
      demonstrated that the abnormal neuronal morphogenesis underlying PHEV infection
      was mainly caused by functional mRNA repression of the miR-142-5p target Ulk1.
      Our data revealed that PHEV adapted to use spatiotemporal control of host
      microRNAs to invade CNS, and provided new insights into the virus-associated
      neurological dysfunction microenvironment.

PMID- 28516069
TI  - Is it Necessary to Perform Nephrostography before Tube Removal after Percutaneous
      Nephrolithotomy.
AB  - BACKGROUND: The aim of this study is the caparison of the complications rate
      among the patients which underwent nephrostomy removal with and without
      performing nephrostography. MATERIALS AND METHODS: Between October 2010 and
      November 2011, 200 patients who underwent standard percutaneous nephrolithotomy
      (PCNL) procedures were included in this study. The patients were randomly
      assigned into two groups, Group A (n = 100) did not undergo the antegrade
      nephrostography on postoperative day 2 and the patients were discharged keeping
      the nephrostomy until postoperative day 3, while in Group B (n = 100) the
      nephrostomy tube was removed on postoperative day 3 after antegrade
      nephrostography demonstrating ureteral drainage down to the bladder.
      Postoperative complications in both groups were recorded and compared between two
      groups. RESULTS: A total of 200 patients were treated with standard PCNL. The
      persistent leakage of urine after removal of the nephrostomy tube was encountered
      in 5 (5.0%) and 3 (3%) of patients in Groups 1 and 2, respectively. Urinary
      leakage was resolved with conservative management in 3 and 2 patients of Groups 1
      and 2, respectively, but a double-J stent was inserted in 2 and 1 patients in
      each group because of persistent leakage of urine more than 1-week. The two
      groups show comparable complications such as prolonged urinary leakage which
      managed in a similar manner, however, postoperative hospital stay was lesser in
      Group 1. CONCLUSION: Our results revealed postoperative performing nephrostogramy
      before tube removal changed the planning of complications such as prolonged
      urinary leakage and could be omitted in cases.

PMID- 28516068
TI  - A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral
      Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of
      Vitiligo Patients.
AB  - BACKGROUND: Vitiligo, a common disorder of depigmentation, is often difficult to
      treat. Corticosteroids are known to be effective, but with modest results.
      Although simvastatin has been reported to be effective for immunorelated
      dermatologic disorders including vitiligo, controlled trials are lacking. This
      study was conducted to compare the efficacy of topical betamethasone valerate
      0.1% cream (as a standard method of treatment for vitiligo) versus a combination
      of betamethasone valerate plus oral simvastatin in the treatment of vitiligo.
      MATERIALS AND METHODS: Eighty-eight subjects with symmetric vitiligo who had body
      surface involvement up to 20% were divided randomly into two groups. Group A were
      treated with betamethasone valerate 01% cream twice daily and Group B with
      betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for
      12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups.
      The results were evaluated by a blind dermatologist using Vitiligo Area Scoring
      Index (VASI) score at baseline, 4th, 8th, and 12th week of treatment. In a
      similar way, subjective assessment performed by patients based on photo
      evaluation at the end of the study. RESULTS: Despite a continuous reduction in
      VASI score in both groups, according to both physician (P = 0.13) and patient (P
      = 0.374) assessment oral simvastatin was not statistically more effective than
      conventional treatment of vitiligo. CONCLUSION: This study indicates that oral
      simvastatin is not associated with significant impacts in the treatment of
      vitiligo as compared to other inflammatory dermatologic conditions such as
      psoriasis. Indeed, other studies should be initiated regarding exact molecular
      and cellular effects of statins in the treatment of vitiligo.

PMID- 28516066
TI  - The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and
      Their Ability to Kill Streptococcus pneumoniae.
AB  - Despite the availability of vaccines, Streptococcus pneumoniae remains a leading
      cause of life-threatening infections, such as pneumonia, bacteremia and
      meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease
      course, because optimal host defense requires an initial robust pulmonary PMN
      response to control bacterial numbers followed by modulation of this response
      later in infection. The elderly, who manifest a general decline in immune
      function and higher basal levels of inflammation, are at increased risk of
      developing pneumococcal pneumonia. Using an aged mouse infection model, we
      previously showed that oral supplementation with the alpha-tocopherol form of
      vitamin E (alpha-Toc) decreases pulmonary inflammation, in part by modulating
      neutrophil migration across lung epithelium into alveolar spaces, and reverses
      the age-associated decline in resistance to pneumococcal pneumonia. The objective
      of this study was to test the effect of alpha-Toc on the ability of neutrophils
      isolated from young (22-35 years) or elderly (65-69 years) individuals to migrate
      across epithelial cell monolayers in response to S. pneumoniae and to kill
      complement-opsonized pneumococci. We found that basal levels of pneumococcal
      induced transepithelial migration by PMNs from young or elderly donors were
      indistinguishable, suggesting that the age-associated exacerbation of pulmonary
      inflammation is not due to intrinsic properties of PMNs of elderly individuals
      but rather may reflect the inflammatory milieu of the aged lung. Consistent with
      its anti-inflammatory activity, alpha-Toc treatment diminished PMN migration
      regardless of donor age. Unexpectedly, unlike previous studies showing poor
      killing of antibody-opsonized bacteria, we found that PMNs of elderly donors were
      more efficient at killing complement-opsonized bacteria ex vivo than their
      younger counterparts. We also found that the heightened antimicrobial activity in
      PMNs from older donors correlated with increased activity of neutrophil elastase,
      a serine protease that is required to kill pneumococci. Notably, incubation with
      alpha-Toc increased PMN elastase activity from young donors and boosted their
      ability to kill complement-opsonized pneumococci. These findings demonstrate that
      alpha-Toc is a potent modulator of PMN responses and is a potential nutritional
      intervention to combat pneumococcal infection.

PMID- 28516070
TI  - Bone Density in Postmenopausal Women with or without Breast Arterial
      Calcification.
AB  - BACKGROUND: Identification of osteoporosis in women in order to prevent its
      related morbidity and mortality is considered a priority. Routine mammography is
      performed on all menopausal women as a screening tool. Determination of the
      relation between breast arterial calcification (BAC) on mammography and the bone
      density of this high-risk population could help us to determine those with
      osteoporosis. The aim of this study was to investigate the mentioned probable
      relation between BAC and osteoporosis. MATERIALS AND METHODS: In this cross
      sectional study, menopausal women referred for annual screening mammography were
      enrolled. According to the results of mammography, they were classified into two
      groups: menopausal women with and without calcification of breast arteries. The
      selected women were referred for bone mineral density (BMD) evaluation by dual
      energy x-ray absorptiometry (DXA). The results of BMD were compared between the
      two studied groups. RESULTS: In this study, BMD was measured in 43 and 45
      menopausal women with and without BAC, respectively. After age adjustment the
      difference between BMD measurements were not statistically significantly
      different (P > 0.05). There was a significant negative correlation between age
      and lumbar (P = 0.002, r = -0.42) and hip bone (P = 0.000, r = -0.67) density in
      menopausal women with BAC. CONCLUSION: The results of the current study indicated
      that there was no significant relationship between BAC and BMD in our studied
      population, but it seems that increasing age has an important role in both
      developing BAC and reducing BMD. For obtaining more conclusive results, further
      studies with larger sample sizes and considering the severity of BAC is
      recommended.

PMID- 28516071
TI  - Levamisole as an Adjuvant to Short-Course Therapy in Newly Diagnosed Pulmonary
      Tuberculosis Patients.
AB  - BACKGROUND: The estimated incidence and prevalence of tuberculosis in India are
      2.1 and 2.6 million cases respectively. Immunotherapy may shorten tuberculosis
      treatments and improve the immunity of individuals as well. Hence we study the
      efficacy of levamisole (LVM) (immunomodulator) as an adjuvant to chemotherapy of
      pulmonary tuberculosis patients. MATERIALS AND METHODS: A randomized, double
      blind, placebo-controlled clinical trial was conducted for 21 months in newly
      diagnosed sputum positive pulmonary tuberculosis patients. Patients were
      subjected initially to clinical examination, sputum acid-fast bacilli smear and
      culture, tuberculin skin test and weight record. During follow-up, above
      investigations were repeated. Sixty-five patients were randomly assigned into two
      groups to receive either tab LVM 100 mg once in a day or matching placebo, orally
      as a single dose, thrice a week, for 2 months with short-course antituberculosis
      chemotherapy. RESULTS: Sputum negativity at 1 week was observed in 11 (44%)
      patients in LVM group whereas only 3 (12%) in placebo group. All the patients 25
      (100%) in LVM group were sputum negative compared to 14 (56%) in placebo group by
      the end of 3 weeks. In LVM group, 24 (96%) and 11 (44%) patients in placebo group
      show radiological improvement at 2 months. A direct correlation existed between
      quantum of immune response and weight gain with LVM. LVM rendered all anergic
      patients to positive tuberculin reactors. In LVM group, patients with initial
      Mantoux >=20 mm and advanced cavitary disease, there was decrease in tuberculin
      reaction size. CONCLUSION: Adjuvant immunomodulation with levamisole has the
      potential of shortening the total duration of antitubercular therapy.

PMID- 28516072
TI  - Bevacizumab in Recurrent Glioma: Patterns of Treatment Failure and Implications.
AB  - Glioblastoma, the most common primary malignant brain tumor in adults, is highly
      aggressive and associated with a poor prognosis. Bevacizumab, a monoclonal
      antibody against the vascular endothelial growth factor receptor, has
      increasingly been used in the treatment of recurrent glioblastoma. It has
      achieved excellent rates of radiographic response, but most patients will
      progress after only a few months. Upon recurrence, tumors may not enhance,
      secondary to vascular normalization. We describe four patterns of radiographic
      progression commonly associated with Bevacizumab failure: 1) Distant enhancing
      tumor, 2) Local tumor progression without enhancement, 3) Diffuse gliomatosis
      like infiltration, and 4) Local or multifocal progression, with enhancement. Some
      have noted an increased incidence of distant or diffuse disease upon recurrence,
      suggestive of a transition to a more aggressive phenotype, but a review of the
      literature suggests there is no conclusive evidence that Bevacizumab treatment is
      associated with an increased rate of distant or diffuse recurrence.

PMID- 28516074
TI  - An Updated Nationwide Epidemiology of Primary Brain Tumors in Republic of Korea,
      2013.
AB  - BACKGROUND: This report aims to provide accurate nationwide epidemiologic data on
      primary brain and central nervous system (CNS) tumors in the Republic of Korea.
      We updated the data by analyzing primary brain and CNS tumors diagnosed in 2013
      using the data from the national cancer incidence database. METHODS: Data on
      primary brain and CNS tumors diagnosed in 2013 were collected from the Korean
      Central Cancer Registry. Crude and age-standardized rates were calculated in
      terms of gender, age, and histological type. RESULTS: A total of 11,827 patients
      were diagnosed with primary brain and CNS tumors in 2013. Brain and CNS tumors
      occurred in females more often than in males (female:male, 1.70:1). The most
      common tumor was meningioma (37.3%). Pituitary tumors (18.0%), gliomas (12.7%),
      and nerve sheath tumors (12.3%) followed in incidence. Glioblastomas accounted
      for 41.8% of all gliomas. In children (<19 years), sellar region tumors
      (pituitary and craniopharyngioma), embryonal/primitive/medulloblastoma, and germ
      cell tumors were the most common tumors. CONCLUSION: This study should provide
      valuable information regarding the primary brain tumor epidemiology in Republic
      of Korea.

PMID- 28515670
TI  - Measurement of the W boson polarisation in [Formula: see text] events from pp
      collisions at [Formula: see text] = 8 TeV in the lepton + jets channel with
      ATLAS.
AB  - This paper presents a measurement of the polarisation of W bosons from [Formula:
      see text] decays, reconstructed in events with one high-[Formula: see text]
      lepton and at least four jets. Data from pp collisions at the LHC were collected
      at [Formula: see text] = 8 TeV and correspond to an integrated luminosity of 20.2
      fb[Formula: see text]. The angle [Formula: see text] between the b-quark from the
      top quark decay and a direct W boson decay product in the W boson rest frame is
      sensitive to the W boson polarisation. Two different W decay products are used as
      polarisation analysers: the charged lepton and the down-type quark for the
      leptonically and hadronically decaying W boson, respectively. The most precise
      measurement of the W boson polarisation via the distribution of [Formula: see
      text] is obtained using the leptonic analyser and events in which at least two of
      the jets are tagged as b-quark jets. The fitted fractions of longitudinal, left-
      and right-handed polarisation states are [Formula: see text], [Formula: see text]
      and [Formula: see text], and are the most precisely measured W boson polarisation
      fractions to date. Limits on anomalous couplings of the Wtb vertex are set.

PMID- 28516073
TI  - Systematic Analysis of Clinical Outcomes Following Stereotactic Radiosurgery for
      Central Neurocytoma.
AB  - Central neurocytoma (CN) typically presents as an intraventricular mass causing
      obstructive hydrocephalus. The first line of treatment is surgical resection with
      adjuvant conventional radiotherapy. Stereotactic radiosurgery (SRS) was proposed
      as an alternative therapy for CN because of its lower risk profile. The objective
      of this systematic analysis is to assess the efficacy of SRS for CN. A systematic
      analysis for CN treated with SRS was conducted in PubMed. Baseline patient
      characteristics and outcomes data were extracted. Heterogeneity and publication
      bias were also assessed. Univariate and multivariate linear regressions were used
      to test for correlations to the primary outcome: local control (LC). The
      estimated cumulative rate of LC was 92.2% (95% confidence interval: 86.5-95.7%,
      p<0.001). Mean follow-up time was 62.4 months (range 3-149 months). Heterogeneity
      and publication bias were insignificant. The univariate linear regression models
      for both mean tumor volume and mean dose were significantly correlated with
      improved LC (p<0.001). Our data suggests that SRS may be an effective and safe
      therapy for CN. However, the rarity of CN still limits the efficacy of a
      quantitative analysis. Future multi-institutional, randomized trials of CN
      patients should be considered to further elucidate this therapy.

PMID- 28516075
TI  - Fourth Ventricular Lesions in Metastatic Gliomas: A Rare Predilection?
AB  - Over the course of five years, a total of ten cases were collected of glioma
      patients in whom a distant lesion at the fourth ventricle was noted. A 'distant
      lesion' was defined as a lesion with a normal appearing tissue bridge at imaging
      between the primary and secondary locations. Previous imaging of these patients
      was reviewed along with clinical history, course of therapy, and available
      histology. A review of the literature was performed with respect to present
      knowledge on patterns of glioma proliferation and dissemination. This case series
      is the first to describe the fourth ventricle as a location that may be prone to
      secondary lesions in glioma patients. Further investigation on this subject may
      yield deeper insights into the mechanisms by which glial tumors spread within the
      brain, with the hope of developing or improving therapeutic targets.

PMID- 28516076
TI  - Primary Central Nervous System Vasculitis Mimicking a Cortical Brain Tumor: A
      Case Report.
AB  - We report a case of primary central nervous system vasculitis (PCNSV) mimicking a
      cortical brain tumor. A 25-year-old woman presented with a 2-week history of
      headache and transient right hemiparesis. Brain magnetic resonance imaging (MRI)
      revealed a cortical-involving lesion on the left frontal lobe. The 6-cm sized
      lesion showed low signal intensity on T1-weighted images and high signal
      intensity on T2-weighted images. The lesion had continual linear enhancement on
      the subcortical white matter and leptomeninges. There was no evidence of
      hemorrhage on susceptibility-weighted images and no diffusion restriction on
      diffusion-weighted images. The regional cerebral blood volume was decreased on
      the MR perfusion images, and spectroscopy showed increased lactate and lipid
      peaks. The symptoms were aggravated by fever and seizures. Biopsy was performed
      to rule out tumorous or inflammatory lesions. Pathologically, lymphocytes were
      infiltrated on the vessels, and the arachnoid membrane was thickened with
      inflammatory cells. The patient did not have any underlying diseases, including
      immune disorders. After high-dose steroid administration, her symptoms improved.
      Two months later, brain MRI showed a reduction in the infiltration of the T2
      hyperintensity lesion with subtle subcortical enhancement. We present a case of
      PCNSV involving the left frontal lobe, showing vasogenic edema, mass effect, and
      subcortical linear contrast enhancement without hemorrhage or infarction.

PMID- 28516077
TI  - Toxoplasmic Encephalitis in Patient with Acquired Immunodeficiency Syndrome.
AB  - Toxoplasmic encephalitis (TE) is an opportunistic infection found in
      immunocompromised patients and TE related cerebral mass lesion is often reported
      in acquired immunodeficiency acquired immunodeficiency syndrome (AIDS) patients.
      However, incidence of TE related AIDS in Korea is still rare and is unfamiliar to
      neurosurgeons. Differential diagnosis is needed to rule out other brain lesions.
      A 39-year-old man visited the emergency room with rapid progressive left
      hemiparesis. Magnetic resonance imaging showed a ring-enhanced mass lesion in his
      right frontal lobe. Human immunodeficiency virus and Toxoplasma gondii
      immunoglobulin G were tested positive by a serologic test. We report here a rare
      case of patient with TE related AIDS.

PMID- 28516079
TI  - Fourth Ventricle Neurenteric Cyst Mimicking Hemangioblastoma.
AB  - This report presents a case of fourth ventricle neurenteric cyst (NE cyst)
      mimicking hemangioblastoma, which developed in a 50-year-old woman. A tiny
      enhancing mural portion of the fourth ventricle in MRI suggested that the cyst
      was hemangioblastoma, but pathological evidence showed that the cyst was in fact
      NE cyst in the fourth ventricle. In order to make proper decision on to what
      extent of surgical resection should be done, considering every possibility in
      differential diagnosis might be helpful. This case reports an unusual pathology
      in 4th ventricle, considering the patient's age, and demonstrates that a rarer
      disease may share radiological features of a common disease.

PMID- 28516084
TI  - Editorial: Health Disparities-An Important Public Health Policy Concern.

PMID- 28516078
TI  - Subependymal Giant Cell Astrocytoma Presenting with Tumoral Bleeding: A Case
      Report.
AB  - We report a rare case of subependymal giant cell astrocytoma (SEGA) associated
      with tumoral bleeding in a pediatric patient without tuberous sclerosis complex
      (TSC). A 10-year-old girl presented with a 2-week history of an increasingly
      aggravating headache. Brain magnetic resonance imaging revealed an approximately
      3.6-cm, well-defined, heterogeneously enhancing mass with multistage hemorrhages
      on the right-sided foramen of Monro. The tumor was completely resected using a
      transcallosal approach. Intraoperatively, the mass presented as a gray-colored
      firm tumor associated with acute and subacute hemorrhages. The origin of the mass
      was identified as the ventricular septum adjacent to the foramen of Monro. A
      pathological analysis revealed pleomorphic multinucleated eosinophilic tumor
      cells with abundant cytoplasm. These cells showed positive staining for the glial
      fibrillary acidic protein and S100 protein. A diagnosis of SEGA was established.
      The patient recovered without any neurological symptoms. There was no evidence of
      TSC. The radiological follow-up showed no recurrence for 2 years. This was a case
      of SEGA with intratumoral hemorrhage, for which a favorable outcome was achieved,
      without any neurological deficit after tumoral resection.

PMID- 28516080
TI  - Cutaneous Anaplastic Large T-Cell Lymphoma with Invasion of the Central Nervous
      System: A Case Report.
AB  - Anaplastic large T-cell lymphoma (ALCL) encompasses different clinical entities
      that can be aggressive or localized. Scalp anaplastic lymphoma kinase (ALK)
      negative ALCL is considered a localized lymphoma, and usually extends to the
      regional lymph nodes; intracranial invasion is rare. A 74-year-old woman was
      diagnosed with scalp ALK-negative ALCL, but did not exhibit invasion of the lymph
      nodes. Computed tomography and magnetic resonance imaging revealed intracranial
      masses with bony erosions. We treated the patient using CHOP chemotherapy and
      achieved short-term regression of the scalp and intracranial lesions. However,
      the patients ultimately died of pneumonia during the pancytopenic period.
      Therefore, caution must be exercised when treating scalp ALK-negative ALCL with
      intracranial invasion.

PMID- 28516081
TI  - A Case of Coincidental Intrasellar Chordoma and Pituitary Adenoma.
AB  - Although chordomas are midline tumors, primarily intrasellar chordomas are
      extremely rare. In this report, the authors describe the case of a 68-year-old
      female with partial abducens nerve palsy in the right eye due to the intrasellar
      cystic tumor. After endonasal trans-sphenoidal surgery, intraoperative and
      histopathological findings confirmed the co-occurrence of an entirely intrasellar
      chordoma and pituitary adenoma. To our knowledge, the present case is the third
      reported case of an intrasellar chordoma with a pituitary adenoma.

PMID- 28516082
TI  - Multifocal Recurrent Osteomyelitis and Hemophagocytic Lymphohistiocytosis in a
      Boy with Partial Dominant IFN-gammaR1 Deficiency: Case Report and Review of the
      Literature.
AB  - Mutations in the genes coding for cytokines, receptors, second messengers, and
      transcription factors of interferon gamma (IFN-gamma) immunity cause Mendelian
      susceptibility to mycobacterial disease (MSMD). We report the case of a 7-year
      old male patient with partial dominant (PD) IFN-gamma receptor 1 deficiency who
      had suffered from multifocal osteomyelitis attributable to bacille Calmette
      Guerin vaccination since the age of 18 months. He developed hemophagocytic
      lymphohistiocytosis (HLH), a hyper-inflammatory complication, and died with
      multiorgan dysfunction, despite having been diagnosed and treated relatively
      early. Patients with PD IFN-gammaR1 deficiency usually have good prognosis and
      might respond to human recombinant subcutaneous IFN-gamma. Several monogenic
      congenital defects have been linked to HLH, a catastrophic "cytokine storm" that
      is usually ascribed to lymphocyte dysfunction and thought to be triggered by
      interferon gamma. This is the sixth patient with both MSMD and HLH of whom we are
      aware. The fact that patients with macrophages that cannot respond to IFN-gamma
      still develop HLH, bring these assumptions into question.

PMID- 28516083
TI  - How to Study Chronic Diseases-Implications of the Convention on the Rights of
      Persons with Disabilities for Research Designs.
AB  - BACKGROUND: The Convention on the Rights of Persons with Disabilities (CRPD) has
      been received considerable attention internationally. METHODS: The Convention's
      main arguments are conceptually analyzed. Implications for the development of
      research designs are elaborated upon. RESULTS: The Convention entails both a
      human rights and a sociopolitical dimension. Advancing a relational notion of
      disability, it enters a rather foreign terrain to medical sciences. Research
      designs have to be changed accordingly. CONCLUSION: Research designs in
      accordance with the CRPD should employ and further develop context-sensitive
      research strategies and interdisciplinary collaboration. Complex designs that
      allow for a relational analysis of personalized effects have to be established
      and evaluated, thereby systematically integrating qualitative methods.

PMID- 28516089
TI  - Distinguished Lecture Given at the Opening of the 5th International Meeting on
      Aortic Disease, Liege, Belgium (September 15, 2016).

PMID- 28516087
TI  - DNA Sequence Analysis in Clinical Medicine, Proceeding Cautiously.
AB  - Delineation of underlying genomic and genetic factors in a specific disease may
      be valuable in establishing a definitive diagnosis and may guide patient
      management and counseling. In addition, genetic information may be useful in
      identification of at risk family members. Gene mapping and initial genome
      sequencing data enabled the development of microarrays to analyze genomic
      variants. The goal of this review is to consider different generations of
      sequencing techniques and their application to exome sequencing and whole genome
      sequencing and their clinical applications. In recent decades, exome sequencing
      has primarily been used in patient studies. Discussed in some detail, are
      important measures that have been developed to standardize variant calling and to
      assess pathogenicity of variants. Examples of cases where exome sequencing has
      facilitated diagnosis and led to improved medical management are presented. Whole
      genome sequencing and its clinical relevance are presented particularly in the
      context of analysis of nucleotide and structural genomic variants in large
      population studies and in certain patient cohorts. Applications involving
      analysis of cell free DNA in maternal blood for prenatal diagnosis of specific
      autosomal trisomies are reviewed. Applications of DNA sequencing to diagnosis and
      therapeutics of cancer are presented. Also discussed are important recent
      diagnostic applications of DNA sequencing in cancer, including analysis of tumor
      derived cell free DNA and exosomes that are present in body fluids. Insights
      gained into underlying pathogenetic mechanisms of certain complex common
      diseases, including schizophrenia, macular degeneration, neurodegenerative
      disease are presented. The relevance of different types of variants, rare,
      uncommon, and common to disease pathogenesis, and the continuum of causality, are
      addressed. Pharmogenetic variants detected by DNA sequence analysis are gaining
      in importance and are particularly relevant to personalized and precision
      medicine.

PMID- 28516090
TI  - Lower Aorto-Iliac Bifurcation Position and Incident Cardiovascular Disease: A
      Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: With increasing age, a downward shift of the aorto-iliac bifurcation
      relative to the lumbar spine occurs. A lower bifurcation position is an
      independent marker for adverse vascular aging and is associated with increased
      burden of cardiovascular disease (CVD) risk factors; however, the associations
      between lower bifurcation position and CVD events remain unknown. METHODS:
      Abdominal computed tomography scans were used to measure the aorto-iliac
      bifurcation distance (AIBD, distance from the aorto-iliac bifurcation to the
      L5/S1 disc space). Cox proportional hazard analysis was used to determine the
      independent hazard of a lower bifurcation position (smaller AIBD) for incident
      coronary heart disease (CHD, defined as myocardial infarction, resuscitated
      cardiac arrest, or sudden cardiac death), CVD (CHD plus stroke or stroke death),
      and all-cause mortality (ACM). RESULTS: In the 1,711 study participants (51%
      male), the mean AIBD was 26 +/- 15 mm. After a median follow-up of 10 years, 63
      (3.7%) developed CHD, 100 (5.8%) developed CVD, and 129 (7.5%) were deceased.
      Compared to the 4th quartile of AIBD (highest bifurcation position), participants
      in the 1st quartile (lowest bifurcation position) had increased risk for CHD
      (hazard ratio (HR) = 1.5, 95% confidence interval (CI): 0.8-3.0, P = 0.2), CVD
      (HR = 1.8, 95% CI: 0.9-2.7, P = 0.1), and ACM (HR = 2.2, 95% CI: 1.3-3.6, P =
      0.01). After adjustments for CVD risk factors, the HR for ACM was no longer
      significant. CONCLUSION: Despite being an independent marker for adverse vascular
      changes in the aorta, a lower aorto-iliac bifurcation position was not
      independently associated with future CVD events. The opposing effects of
      atherosclerosis and stiffness in the aorta may, in part, explain our null
      findings.

PMID- 28516085
TI  - Analysis of Septin Reorganization at Cytokinesis Using Polarized Fluorescence
      Microscopy.
AB  - Septins are conserved filament-forming proteins that act in diverse cellular
      processes. They closely associate with membranes and, in some systems, components
      of the cytoskeleton. It is not well understood how filaments assemble into higher
      order structures in vivo or how they are remodeled throughout the cell cycle. In
      the budding yeast S. cerevisiae, septins are found through most of the cell cycle
      in an hourglass organization at the mother-bud neck until cytokinesis when the
      collar splits into two rings that disassemble prior to the next cell cycle.
      Experiments using polarized fluorescence microscopy have suggested that septins
      are arranged in ordered, paired filaments in the hourglass and undergo a
      coordinated 90 degrees  reorientation during splitting at cytokinesis. This
      apparent reorganization could be due to two orthogonal populations of filaments
      disassembling and reassembling or being preferentially retained at cytokinesis.
      In support of this idea, we report a decrease in septin concentration at the
      mother-bud neck during cytokinesis consistent with other reports and the timing
      of the decrease depends on known septin regulators including the Gin4 kinase. We
      took a candidate-based approach to examine what factors control reorientation
      during splitting and used polarized fluorescence microscopy to screen mutant
      yeast strains deficient in septin interacting proteins. Using this method, we
      have linked known septin regulators to different aspects of the assembly,
      stability, and reorganization of septin assemblies. The data support that ring
      splitting requires Gin4 activity and an anillin-like protein Bud4, and normal
      accumulation of septins at the ring requires phosphorylation of Shs1. We found
      distinct regulatory requirements for septin organization in the hourglass
      compared to split rings. We propose that septin subpopulations can vary in their
      localization and assembly/disassembly behavior in a cell-cycle dependent manner
      at cytokinesis.

PMID- 28516093
TI  - Iatrogenic Supravalvular Aortic Stenosis.
AB  - We describe a case of hemolytic anemia and proximal anastomotic site stenosis
      following emergency repair of a Type A aortic dissection. This rare complication
      led to a reoperation to correct the iatrogenic aortic stenosis and cure the
      consequent hemolysis. A "sandwich" technique (with two Teflon strips on the
      outside and inside of the aortic wall) was used in the initial repair to
      reinforce the suture line and prevent bleeding from the aortic anastomoses. At
      the time of reoperation, the inner Teflon strip at the proximal aortic
      anastomosis was found to have inverted into the aortic lumen, as suggested by the
      preoperative magnetic resonance imaging. Surgical treatment consisted of
      resecting the portion of inner Teflon that had turned in and tacking the
      remaining part back onto the aortic wall. The observed hemolysis was likely due
      to the turbulent flow associated with the supra-aortic stenosis and the collision
      of red cells with the internal Teflon strip. The patient made an uncomplicated
      recovery with no further hemolysis and was discharged on postoperative day 8.

PMID- 28516094
TI  - Combined Transapical Transcatheter Aortic Valve Replacement and Thoracic
      Endovascular Aortic Repair for Severe Aortic Stenosis and Arch Aneurysm.
AB  - An 83-year-old male with multiple comorbidities presented with critical aortic
      stenosis and a saccular aortic arch aneurysm. Through a mini thoracotomy, a
      balloon expandable transcatheter aortic valve was delivered transapically. A
      thoracic stent graft was then delivered through the prosthetic valve and deployed
      in the arch, while a covered stent was deployed in the left common carotid
      artery. Three-year postoperative computed tomography showed a thrombosed arch
      aneurysm with decreased size. This case demonstrates the feasibility of using
      combined transapical transcatheter technologies to treat multicomponent disease
      in a high-risk patient during a single operation.

PMID- 28516088
TI  - The Candida albicans Biofilm Matrix: Composition, Structure and Function.
AB  - A majority of infections caused by Candida albicans-the most frequent fungal
      pathogen-are associated with biofilm formation. A salient feature of C. albicans
      biofilms is the presence of the biofilm matrix. This matrix is composed of
      exopolymeric materials secreted by sessile cells within the biofilm, in which all
      classes of macromolecules are represented, and provides protection against
      environmental challenges. In this review, we summarize the knowledge accumulated
      during the last two decades on the composition, structure, and function of the C.
      albicans biofilm matrix. Knowledge of the matrix components, its structure, and
      function will help pave the way to novel strategies to combat C. albicans biofilm
      infections.

PMID- 28516095
TI  - David-V Procedure in a Patient with Aortic Dilation and Competent Quadricuspid
      Aortic Valve: Are Genetics to Blame?
AB  - Quadricuspid aortic valves (QAVs) are extremely rare. In this case study, we
      report a David-V valve-sparing aortic root replacement with reimplantation of a
      native QAV in a patient with aortic dilation, normal valve function, and a family
      history of aortic dissection. Microscopic pathological examination of the excised
      section of the aorta revealed scattered small foci of cystic medical degeneration
      throughout. A genetic predisposition for aortic dilation may be present in
      patients with QAV, even in the setting of a competent valve. Regular screening
      for aortic dilation in patients with known QAV should therefore be considered.

PMID- 28516091
TI  - Treatment of Dacron Grafting Dilatation with Endovascular Stent Grafting.
AB  - Dacron grafts are frequently used during surgical revascularization procedures.
      Complications including graft thrombosis and infection are well known; however,
      aneurysm formation is extremely rare. In this report, we describe dilatation of a
      Dacron graft detected four years after aortobifemoral bypass procedure in a 50
      year-old male patient who was treated with endovascular stent grafting.

PMID- 28516092
TI  - Frozen Elephant Trunk and Antegrade Visceral Debranching in the Surgical
      Treatment of Type B Aortic Dissection: An Alternative Method.
AB  - Intervention is inevitable in complicated Type B aortic dissections. Classical
      surgical procedures and endovascular interventions are far from ideal treatments
      due to their high risk of periprocedural complications and mortality. There is
      often a need for alternative method in cases of difficult anatomy. We present the
      combined use of frozen elephant trunk and antegrade visceral debranching methods
      in the treatment of a 54-year-old male patient with complicated Type B aortic
      dissection.

PMID- 28516096
TI  - Page for the General Public.

PMID- 28516086
TI  - Can Synovial Pathobiology Integrate with Current Clinical and Imaging Prediction
      Models to Achieve Personalized Health Care in Rheumatoid Arthritis?
AB  - Although great progress has been made in the past decade toward understanding the
      pathogenesis of rheumatoid arthritis (RA), clinicians remain some distance from a
      goal of personalized health care. The capacity to diagnose RA early, predict
      prognosis, and moreover predict response to biologic therapies has been a
      research focus for many years. How currently available clinical prediction models
      can facilitate such goals is reviewed in this article. In addition, the role of
      current imaging techniques in this regard is also discussed. Finally, the authors
      review the current literature regarding synovial biomarkers and consider whether
      integration of synovial pathobiology into clinical prediction algorithms may
      enhance their predictive value.

PMID- 28516097
TI  - Asymmetric Dimethylarginine in Patients with Ascending Aortic Aneurysms.
AB  - BACKGROUND: Ascending thoracic aortic aneurysm (aTAA) is a heterogeneous group of
      disorders that involve impaired endothelial function. The nitric oxide (NO)
      synthase inhibitor asymmetric dimethylarginine (ADMA) serves as an endothelial
      dysfunction marker. Thus, we investigated ADMA levels in patients with aTAA.
      METHODS: Eighty-six patients with aTAA and 18 healthy individuals were enrolled.
      All patients underwent echocardiography. Plasma ADMA levels were measured using
      high-performance liquid chromatography. RESULTS: ADMA levels were higher in aTAA
      patients than in control patients (p = 0.034). According to the multivariable
      regression model, higher ADMA levels were associated with ascending aortic
      diameter (p = 0.017), smoking (p = 0.016), and log-transformed estimated
      glomerular filtration rate (eGFR, p = 0.005). CONCLUSION: This pilot study
      demonstrates an association of ADMA with ascending aortic dilatation; however,
      further studies are needed to investigate whether increased ADMA levels underlie
      aTAA development.

PMID- 28516098
TI  - Spontaneous Regression of a Large Iatrogenic Dissection of the Ascending Aorta.
AB  - A 74-year-old woman was admitted for right coronary angioplasty. During the
      procedure, she complained about chest pain, and contrast injection showed an
      iatrogenic dissection of the ascending aorta. A contrast computed tomography (CT)
      scan confirmed the diagnosis via visualization of a large non-circulating false
      lumen, which involved nearly the entire ascending aorta. The patient remained
      hemodynamically stable and asymptomatic while receiving medical therapy alone.
      Another CT scan performed 3 days later showed complete regression of the false
      lumen. This case suggests that uncomplicated iatrogenic dissection of the
      ascending aorta, even when large, may be managed successfully by medical therapy.

PMID- 28516099
TI  - Conservative Management of Extensive Iatrogenic Aortic Dissection.
AB  - Iatrogenic aortic dissection (IAD) is a rare complication of percutaneous
      coronary interventions (PCI). There are no clear guidelines for IAD management,
      and limited data are available. Registry data and case series combined with
      extrapolations from our experience with spontaneous Type-A dissections suggest
      that very limited dissections are often managed conservatively with coronary
      stenting of the entry tear when possible, while more extensive dissections are
      managed surgically. We present a case report of a 50-year-old woman who underwent
      PCI for an ST-elevation myocardial infarction that resulted in an extensive IAD
      from the ostium of the right coronary artery to the aortic root, ascending aorta,
      and aortic arch. While the current evidence strongly supports surgical management
      of such extensive dissection, our patient was successfully managed conservatively
      with complete resolution according to short-term computed tomography imaging.
      This case suggests that conservative management may be a reasonable approach for
      select patients with extensive IAD.

PMID- 28516100
TI  - Transient Aortic Intramural Hematoma Complicating Transaortic Valve Replacement.
AB  - Acute aortic intramural hematoma, which is a variant of acute aortic syndromes,
      most frequently occurs spontaneously and typically is treated similar to classic
      aortic dissection. Here, we describe a case in which an iatrogenic aortic
      intramural hematoma occurs shortly after transaortic valve replacement. The
      patient was managed conservatively, and the hematoma quickly resolved as
      demonstrated by serial imaging.

PMID- 28516101
TI  - Early Spontaneous Resolution of an Iatrogenic Acute Type A Aortic Dissection.
AB  - Acute aortic dissection is a rare but devastating complication during cardiac
      catheterization. We present the case of an elderly female who incurred a Stanford
      Type A/DeBakey Type I acute aortic dissection extending into the arch vessels and
      descending aorta likely occurring during right coronary artery engagement for
      angioplasty. The patient was treated successfully by immediately sealing the
      entrance of the dissection via the placement of a stent and anti-impulse therapy.
      Follow-up computed tomography scan showed complete resolution of the dissection
      within one month.

PMID- 28516102
TI  - Iatrogenic Aortic Dissection: Review of the Literature.

PMID- 28516103
TI  - Simplified Approach for Repair of Early Pseudoaneurysm of the Left Coronary
      Button Following Composite Graft Due to Acute Type A Aortic Dissection.
AB  - We present a simplified surgical technique that was performed on a 37-year-old
      man who presented with a pseudoaneurysm of the left coronary ostium two months
      after repair of acute Type A aortic dissection with a composite graft.
      Intraoperatively, the surgical sites showed extreme adhesions. The leakage at the
      level of the coronary suture line was exposed from inside the aortic graft.
      Repair was performed using 7.0 polypropylene sutures, and the postoperative
      course was uneventful. The patient was discharged on postoperative day six
      without further complications.

PMID- 28516104
TI  - Minimalist' Trans-Aneurysmal Approach to Coronary Button Pseudoaneurysm.

PMID- 28516105
TI  - Page for the General Public.

PMID- 28516106
TI  - A Cost-Effectiveness Analysis of Surgical Treatment Modalities for Chondral
      Lesions of the Knee: Microfracture, Osteochondral Autograft Transplantation, and
      Autologous Chondrocyte Implantation.
AB  - BACKGROUND: Numerous surgical options exist to treat chondral lesions in the
      knee, including microfracture (MFx), osteochondral autograft transplantation
      (OAT), first-generation autologous chondrocyte implantation (ACI-1), and next
      generation ACI (ACI-2). PURPOSE: To compare the cost-effectiveness of MFx, OAT,
      and ACI-1. The secondary purpose of this study was to compare the functional
      outcomes of MFx, OAT, ACI-1, and ACI-2. STUDY DESIGN: Systematic review; Level of
      evidence, 2. METHODS: Two independent reviewers conducted an online literature
      search of 2 databases for level 1 and 2 studies using the Lysholm, International
      Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score
      (KOOS), and/or Hospital for Special Surgery (HSS) Knee Score. A weighted mean
      difference in pre- to postoperative functional outcome score was calculated for
      each treatment. The mean per-patient costs associated with MFx, OAT, and ACI-1
      were determined from a recent publication based on review of a national private
      insurance database. The cost for each procedure was then divided by the weighted
      mean difference in functional outcome score to give the cost-per-point change in
      outcome score. RESULTS: A total of 12 studies (6 level 1, 6 level 2) met the
      inclusion criteria for the functional outcome analysis, including 730 knees (MFx,
      n = 300; OAT, n = 90; ACI-1, n = 68; ACI-2, n = 272). The mean follow-up was not
      significantly different between groups (MFx, 29.4 months; OAT, 38.3 months; ACI
      1, 19.0 months; ACI-2, 26.7 months). The mean increase in functional outcome
      score was 23 for MFx, 19 for OAT, 20 for ACI-1, and 35 for ACI-2. The change in
      functional outcome score was significantly greater for ACI-2 when compared with
      all other treatments (P < .0001). The cost-per-point change in functional outcome
      score was $200.59 for MFx, $313.84 for OAT, and $536.59 for ACI-1. CONCLUSION:
      MFx, OAT, ACI-1, and ACI-2 are effective surgical procedures for the treatment of
      cartilage defects in the knee. All 4 treatments led to an increase in functional
      outcome scores postoperatively with a short-term follow-up. ACI-2 had a
      statistically greater improvement in functional outcome scores as compared with
      the other 3 procedures. MFx was found to be the most cost-effective treatment
      option and ACI-1 the least cost-effective.

PMID- 28516107
TI  - Building a central nervous system: The neural stem cell lineage revealed.
AB  - Neural stem cells (NSCs) are a multipotent, self-renewing source of
      undifferentiated cells in the periventricular region of the mammalian central
      nervous system (CNS). Since their original discovery 25 years ago, much has been
      learned about their development, persistence, localization, properties and
      potential. Herein we discuss the current state of knowledge pertaining to neural
      stem cells with a focus on the lineage relationship between two NSC populations
      along the neuraxis and their regionally distinct niches in the CNS.

PMID- 28516109
TI  - Serum-Derived Bovine Immunoglobulin as Novel Adjunct in Complicated Clostridium
      difficile Colitis Treatment.
AB  - Clostridium difficile infection (CDI) is a well-known complication of antibiotic
      therapy. It is associated with significant morbidity, mortality, and cost in the
      hospital setting. The main symptoms include watery diarrhea, abdominal pain, and
      distension, but CDI can also present as toxic megacolon, bowel perforation with
      peritonitis, sepsis and renal failure. Therapy includes metronidazole and oral
      vancomycin, with rectal vancomycin and fecal transplant reserved for more
      complicated cases. Adjunctive treatments such as probiotics have been tried with
      mixed results. We present a patient with complicated CDI treated with adjuvant
      serum-derived bovine immunoglobulin, a novel approach in this context.

PMID- 28516110
TI  - Large Bowel Obstruction following Endoscopic Spray Cryotherapy for Palliation of
      Rectal Cancer Bleeding.
AB  - We report a unique case of a 79-year-old woman with metastatic rectal cancer who
      developed bowel obstruction following endoscopic cryotherapy with liquid nitrogen
      for palliation of bleeding in the rectum. She developed abdominal distention and
      pain following the procedure. Computed tomography of the abdomen revealed a
      paraumbilical hernia containing a segment of transverse colon resulting in
      partial bowel obstruction. It appears that the recurrent freeze-thaw cycles with
      poor decompression of the colon despite active venting suction during cryotherapy
      may have resulted in bowel distention and collapse, causing conformational
      changes resulting in partial bowel obstruction due to a paraumbilical hernia.

PMID- 28516108
TI  - What is CAR doing in the middle of the adult neurogenic road?
AB  - The molecular and cellular basis of adult neurogenesis has attracted considerable
      attention for fundamental and clinical applications because neural stem cells and
      newborn neurons may, one day, be harnessed to replace neurons and allow cognitive
      improvement in the diseased brain. In rodents, neural progenitors are located in
      the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the
      generation of newborn neurons is associated with plasticity, including regulation
      of memory. The role of subventricular zone neural precursors that migrate to the
      olfactory bulb is less characterized. Identifying factors that impact neural stem
      cell proliferation, migration and differentiation is therefore sine qua non
      before we can harness their potential. Here, we expand upon our recent results
      showing that CAR, the coxsackievirus and adenovirus receptor, is among the
      developing list of key players when it comes to the complex process of
      integrating newborn neurons into existing circuits in the mature brain.

PMID- 28516111
TI  - Transhiatal Herniation of the Pancreas: A Rare Cause of Acute Pancreatitis.
AB  - Transhiatal herniation of the pancreas is rare. Acute pancreatitis secondary to
      this phenomenon is particularly unusual. A 102-year-old woman presented with 1
      day of severe chest pain, vomiting, dyspnea, and diaphoresis. Serum lipase was
      elevated, and computed tomography angiogram of the chest and magnetic resonance
      cholangiopancreatography revealed a hiatal hernia containing the pancreas, with
      associated findings of pancreatitis. Pancreatitis in this setting may be due to
      repetitive trauma or ischemia from sliding, intermittent folding of the
      pancreatic duct, or pancreatic incarceration. Mild cases can be managed
      supportively, with surgery being reserved for severe cases or for younger
      patients with low surgical risk.

PMID- 28516112
TI  - Hemorrhagic Cystitis in a Liver Transplant Recipient Secondary to BK Virus.
AB  - The association between BK virus infection and hemorrhagic cystitis (HC) in
      hematopoietic stem cell transplant (HSCT) recipients is well established.
      However, BK virus-associated HC has not been described in liver transplant (LT)
      recipients. We present a case of BK virus-associated HC in a LT recipient. Our
      patient presented with worsening liver function tests 2 years after
      transplantation and was found to have acute cellular rejection. He was treated
      with increased immunosuppression and subsequently developed hematuria. He was
      eventually diagnosed with BK virus-associated HC.

PMID- 28516113
TI  - Pit Assay to Measure the Bone Resorptive Activity of Bone Marrow-derived
      Osteoclasts.
AB  - Although it is possible to use a tartrate-resistant acid phosphatase (TRAP) stain
      to assist in identifying osteoclasts, a separate method is needed to determine
      the bone resorption activity of osteoclasts. Since osteoclasts leave "pits" after
      bone matrix resorption (Charles et al., 2014), it is possible to stain pits as a
      method of measuring osteoclast bone resorption activity. The pit assay protocol
      enables researchers to stain bony slices that were co-cultured with osteoclasts
      with toluidine blue in order to allow the visualization, capture, and analysis of
      osteoclast resorptive activity based on the number, size and depth of pits (Zhou
      et al., 2015). The pit assay protocol is separated into three sequential stages:
      Preparation of bone slices (1); preparation of osteoclast precursors (Ross et
      al., 2006; Teitelbaum et al., 2000) (2), and bone resorption pit assay (3).

PMID- 28516114
TI  - Measurement of mRNA Decay in Mouse Embryonic Fibroblasts.
AB  - mRNA stability control is a critical step in the post-transcriptional regulation
      of gene expression. Actinomycin D, an antibiotic initially used as an anti-cancer
      drug, has turned out to be a convenient tool for studying the turnover rates of
      transcripts in cells, due to its inhibition of mRNA synthesis. Here, we describe
      a protocol for the measurement of mRNA decay after adding actinomycin D into the
      medium of stable fibroblast cell lines derived from wild-type and tristetraprolin
      (TTP)-deficient mouse embryonic fibroblast (MEF) cultures, as well as a protocol
      for determining the relative transcript abundance using semi-quantitative real
      time RT-PCR. Northern blotting or NanoString n-Counter are alternative methods to
      measure mRNA abundance, which is quantified using a phosphorimager in the former
      case. This protocol is suitable for studying primary cultured cells and stable
      cell lines derived from transgenic mice and their respective controls, and
      provides for direct comparisons of mRNA decay rates in otherwise identical cells
      with and without the gene of interest.

PMID- 28516115
TI  - A Modified Chromogenic Assay for Determination of the Ratio of Free Intracellular
      NAD+/NADH in Streptococcus mutans.
AB  - Nicotinamide adenine dinucleotide is a coenzyme present in all kingdoms of life
      and exists in two forms: oxidized (NAD+) and reduced (NADH). NAD(H) is involved
      in a multitude of essential metabolic redox reactions, providing oxidizing or
      reducing equivalents. The ratio of free intracellular NAD+/NADH is fundamentally
      important in the maintenance of cellular redox homeostasis (Ying, 2008). Various
      chromogenic cycling assays have been used to determine the ratio of NAD+/NADH in
      both bacterial and mammalian cells for more than forty years (Bernofsky and Swan,
      1973; Nisselbaum and Green, 1969). Here, we describe in detail an assay to
      determine the ratio of free intracellular NAD+ to NADH in Streptococcus mutans.
      This cycling assay is a modified version of the protocol first described by
      Bernofsky and Swan (Bernofsky and Swan, 1973), using the extraction buffer
      described by Frezza et al. (2011), followed by the reduced MTT precipitation
      described by Gibbon and Larher (Gibon and Larher, 1997). As depicted in Figure 1,
      alcohol dehydrogenase is used to drive a series of redox reactions utilizing
      exogenously added ethanol and NAD+ from sample extracts as initial substrates,
      phenazine ethosulfate (PES) as an electron carrier, and thiazolyl blue
      tetrazolium bromide (MTT) as a terminal electron acceptor. 6 M NaCl is used to
      stop the reaction. The reduced MTT (formazan dye) is purple in color and can be
      quantified by measuring absorbance at 570 nm. This protocol is divided into three
      steps: A. Preparation of cell pellets of S. mutans; B. Preparation of
      deproteinated cell extracts containing NADtotal or NADH; C. NAD+/NADH cycling
      assay. This method has proven robust in measuring the NAD+/NADH ratio in S.
      mutans under a variety of conditions, and should be applicable to other Gram
      positive bacteria.

PMID- 28516116
TI  - ASC-particle-induced Peritonitis.
AB  - In response to pathogen infection and tissue damage, inflammasome sensors such as
      NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC
      nucleation, followed by self-perpetuating ASC polymerization, which ultimately
      culminates in caspase-1 activation, interleukin (IL)-1beta and IL-18 processing
      and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014).
      Inflammasomes release not only cytokines, but also the polymeric ASC danger
      particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome
      responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja
      Mazo et al., 2014; Franklin et al., 2014). In this protocol we describe
      intraperitoneal injection of polymeric ASC particles as a danger signal and
      measure neutrophil infiltration and levels of the pro-inflammatory cytokine IL
      1beta by ELISA in the peritoneal lavage (de Almeida et al., 2015).

PMID- 28516117
TI  - Reconstruction of the Mouse Inflammasome System in HEK293T Cells.
AB  - The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein
      complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis
      associated speck-like protein containing a CARD (ASC), and the protein kinase
      NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et
      al., 2016). When cells are exposed to microbes and/or danger signals, the
      inflammasome assembles and serves as a platform for the activation of caspase-1.
      Caspase-1 activation promotes the processing and secretion of the pro
      inflammatory cytokines interleukin-1beta (IL-1beta), IL-18, and IL-33 as well as
      pyroptosis induction (Gross et al., 2011; Arend et al., 2008), which elicit
      inflammatory responses. Here, we describe how to co-transfect the NLRP3
      inflammasome components into HEK293T cells, which enables inflammasome activation
      and the production of IL-1beta upon stimulation with nigericin.

PMID- 28516118
TI  - Quantitative Measurements of HIV-1 and Dextran Capture by Human Monocyte-derived
      Dendritic Cells (MDDCs).
AB  - : The aim of this protocol is to describe how to measure and quantify the amount
      of HIV-1 particles and dextran molecules internalized in human monocyte derived
      dendritic cells (MDDCs), using three different techniques: flow cytometry,
      quantitative PCR and confocal microscopy. BACKGROUND: This protocol was developed
      in order to assess the changes of HIV-1 internalization upon disruption of actin
      nucleation in human monocyte derived dendritic cells. Following a shRNA screen to
      identify genes important for HIV-1 transfer from dendritic cells to T cells, we
      observed that a disruption of actin nucleation leads to a switch from actin rich
      dendrites to blebs, due to an excess of actomyosin contraction. As a consequence,
      a decrease of HIV-1 transfer and an increase of HIV-1 internalization due to bleb
      retraction-driven macropinocytosis were observed. We concluded that effectors of
      actin nucleation and stabilization were key to maintain HIV-1 on actin-rich
      dendrites and to limit its endocytosis, for efficient transfer to T lymphocytes
      (Menager and Littman, 2016).

PMID- 28516119
TI  - Affinity Pulldown of Biotinylated RNA for Detection of Protein-RNA Complexes.
AB  - RNA-binding proteins (RBPs) have recently emerged as crucial players in the
      regulation of gene expression. The interactions of RBPs with target mRNAs control
      the levels of gene products by altering different regulatory steps, including pre
      mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and
      translation (Glisovic et al., 2008). There are several methodologies available
      today to identify RNAs bound to specific RBPs; some detect only recombinant
      molecules in vitro, others detect recombinant and endogenous molecules, while
      others detect only endogenous molecules. Examples include systematic evolution of
      ligands by exponential enrichment (SELEX), biotinylated RNA pulldown assay, RNA
      immunoprecipitation (RIP) assay, electrophoretic mobility shift assay (EMSA), RNA
      footprinting analysis, and various UV crosslinking and immunoprecipitation (CLIP)
      methods such as CLIP, PAR-CLIP, and iCLIP (Popova et al., 2015). Here, we
      describe a simple and informative method to study and identify the RNA region of
      interaction between an RBP and its target transcript (Panda et al., 2014 and
      2016). Its reproducibility and ease of use make this protocol a fast and useful
      method to identify interactions between RBPs and specific RNAs.

PMID- 28516120
TI  - Abeta Extraction from Murine Brain Homogenates.
AB  - This protocol details beta-amyloid (Abeta) extraction from transgenic murine
      brain homogenates. Specifically, mechanical homogenization of brain tissue and
      sequential extraction of both soluble and insoluble proteins are detailed. DEA
      extracts soluble proteins, such as Abeta isoforms and APP. Formic acid enables
      extraction of insoluble protein aggregates, such as Abeta isoforms associated
      with plaques. This procedure produces soluble and insoluble extracts that are
      amenable to analysis of Abeta species via western blotting and/or enzyme-linked
      immunosorbent assays (ELISAs), and these results help assess amyloidogenic burden
      in animals.

PMID- 28516121
TI  - Simultaneous Intranasal/Intravascular Antibody Labeling of CD4+ T Cells in Mouse
      Lungs.
AB  - CD4+ T cell responses have been shown to be protective in many respiratory virus
      infections. In the respiratory tract, CD4+ T cells include cells in the airway
      and parenchyma and cells adhering to the pulmonary vasculature. Here we discuss
      in detail the methods that are useful for characterizing CD4+ T cells in
      different anatomic locations in mouse lungs.

PMID- 28516123
TI  - Polysome Fractionation to Analyze mRNA Distribution Profiles.
AB  - Eukaryotic cells adapt to changes in external or internal signals by precisely
      modulating the expression of specific gene products. The expression of protein
      coding genes is controlled at the transcriptional and post-transcriptional
      levels. Among the latter steps, the regulation of translation is particularly
      important in cellular processes that require rapid changes in protein expression
      patterns. The translational efficiency of mRNAs is altered by RNA-binding
      proteins (RBPs) and noncoding (nc)RNAs such as microRNAs (Panda et al., 2014a and
      2014b; Abdelmohsen et al., 2014). The impact of factors that regulate selective
      mRNA translation is a critical question in RNA biology. Polyribosome (polysome)
      fractionation analysis is a powerful method to assess the association of
      ribosomes with a given mRNA. It provides valuable information about the
      translational status of that mRNA, depending on the number of ribosomes with
      which they are associated, and identifies mRNAs that are not translated (Panda et
      al., 2016). mRNAs associated with many ribosomes form large polysomes that are
      predicted to be actively translated, while mRNAs associated with few or no
      ribosomes are expected to be translated poorly if at all. In sum, polysome
      fractionation analysis allows the direct determination of translation
      efficiencies at the level of the whole transcriptome as well as individual mRNAs.

PMID- 28516122
TI  - Two-electrode Voltage-clamp Recordings in Xenopus laevis Oocytes: Reconstitution
      of Abscisic Acid Activation of SLAC1 Anion Channel via PYL9 ABA Receptor.
AB  - Two-Electrode Voltage-Clamp (TEVC) recording in Xenopus laevis oocytes provides a
      powerful method to investigate the functions and regulation of ion channel
      proteins. This approach provides a well-known tool to characterize ion channels
      or transporters expressed in Xenopus laevis oocytes. The plasma membrane of the
      oocyte is impaled by two microelectrodes, one for voltage sensing and the other
      one for current injection. Here we list a protocol that allows robust
      reconstitution of multi-component signaling pathways. This protocol has been used
      to study plant ion channels, including the SLAC1 channel (SLOW ANION CHANNEL
      ASSOCIATED 1), in particular SLAC1 activation by either the protein kinase OST1
      (OPEN STOMATA 1), Ca2+-dependent protein kinases (CPKs) or the GHR1 (GUARD CELL
      HYDROGEN PEROXIDE-RESISTANT 1) transmembrane receptor-like protein. Data are
      presented showing reconstitution of abscisic acid activation of the SLAC1 anion
      channel by the 'monomeric' ABA (abscisic acid) receptor RCAR1/PYL9 (PYRABACT
      INRESISTANCE1 [PYR1]/PYR1-LIKE [PYL]/REGULATORYCOMPONENTS OF ABA RECEPTORS
      [RCAR]) by co-expressing four components of the abscisic acid signaling core.
      This protocol is also suitable for studying other ion channel functions and
      regulation mechanisms, as well as transporter proteins.

PMID- 28516124
TI  - Bioinformatic Analysis for Profiling Drug-induced Chromatin Modification
      Landscapes in Mouse Brain Using ChlP-seq Data.
AB  - Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP
      seq) is a powerful technology to profile genome-wide chromatin modification
      patterns and is increasingly being used to study the molecular mechanisms of
      brain diseases such as drug addiction. This protocol discusses the typical
      procedures involved in ChIP-seq data generation, bioinformatic analysis, and
      interpretation of results, using a chronic cocaine treatment study as a template.
      We describe an experimental design that induces significant chromatin
      modifications in mouse brain, and the use of ChIP-seq to derive novel information
      about the chromatin regulatory mechanisms involved. We describe the bioinformatic
      methods used to preprocess the sequencing data, generate global enrichment
      profiles for specific histone modifications, identify enriched genomic loci, find
      differential modification sites, and perform functional analyses. These ChIP-seq
      analyses provide many details into the chromatin changes that are induced in
      brain by chronic exposure to cocaine, and generates an invaluable source of
      information to understand the molecular mechanisms underlying drug addiction. Our
      protocol provides a standardized procedure for data analysis and can serve as a
      starting point for any other ChIP-seq projects.

PMID- 28516125
TI  - Determination of the in vitro Sporulation Frequency of Clostridium difficile.
AB  - The anaerobic, gastrointestinal pathogen, Clostridium difficile, persists within
      the environment and spreads from host-to-host via its infectious form, the spore.
      To effectively study spore formation, the physical differentiation of vegetative
      cells from spores is required to determine the proportion of spores within a
      population of C. difficile. This protocol describes a method to accurately
      enumerate both viable vegetative cells and spores separately and subsequently
      calculate a sporulation frequency of a mixed C. difficile population from various
      in vitro growth conditions (Edwards et al., 2016b).

PMID- 28516126
TI  - An HPLC-based Method to Quantify Coronatine Production by Bacteria.
AB  - Coronatine is a polyketide phytotoxin produced by several pathovars of the plant
      pathogenic bacterium Pseudomonas syringae. It is one of the most important
      virulence factors determining the success of bacterial pathogenesis in the plant
      at both epiphytic and endophytic stages of the disease cycle. This protocol
      describes an optimized procedure to culture bacterial cells for coronatine
      production and to quantify the amount of coronatine secreted in the culture
      medium using an HPLC-based method.

PMID- 28516127
TI  - A Pilot Study for Linking Adolescent Patients to an Interactive Tobacco
      Prevention Program.
AB  - CONTEXT: The American Academy of Pediatrics and professional guidelines recommend
      intervening with adolescents about avoiding tobacco use in the health-care
      setting. Barriers in the clinical setting limit consistent provision of this
      critical service. OBJECTIVES: This pilot study compared 2 approaches for
      referring adolescents to an evidence-based tobacco prevention and cessation
      program in the outpatient setting. Secondary aims assessed tobacco use,
      knowledge, and program evaluation. DESIGN SETTING AND PARTICIPANTS: The study
      setting was a medical and dental clinic. Participants aged 13 to 18 received
      tobacco advice and instructions to work through "A Smoking Prevention Interactive
      Experience." The program addresses health concerns of adolescents about tobacco
      use and is founded on behavioral change theories. The link to access it is
      featured on the website of the National Cancer Institute's Research-Tested
      Interventions. Participants (N = 197) were randomized to 1 of 2 approaches (ie, a
      program link via e-mail or referral by a printed card). RESULTS: The program was
      accessed by 57% (112 of 197) of participants. Both referral approaches were
      equally effective. Non-Hispanics were twice as likely to access the program as
      Hispanics (adjusted odds ratio = 2.1, 95% confidence interval = 1.2-3.8, P <
      .05). Over 95% of participants identified themselves as nonusers of tobacco and
      evaluated the program as beneficial in increasing knowledge and motivation to
      remain tobacco-free. CONCLUSION: Linking adolescent patients to an evidence-based
      tobacco prevention/cessation program at a community health clinic was highly
      promising and feasible. We present conclusions for future research.

PMID- 28516128
TI  - Parental Experiences of Raising a Child With Medium Chain Acyl-CoA Dehydrogenase
      Deficiency.
AB  - Newborn screening enabling early diagnosis of medium chain acyl-CoA dehydrogenase
      deficiency (MCADD) has dramatically improved health outcomes in children with
      MCADD. Achieving those outcomes depends on effective management by parents.
      Understanding parental management strategies and associated anxieties and
      concerns is needed to inform provision of appropriate care and support.
      Semistructured interviews were conducted with a purposive sample of parents of
      children aged 2 to 12 years. Thematic analysis identified two main themes.
      Managing dietary intake examined how parents managed day-to-day dietary intake to
      ensure adequate intake and protection of safe fasting intervals. Managing and
      preventing illness events explored parental experiences of managing illness
      events and their approach to preventing these events. Management strategies were
      characterized by caution and vigilance and influenced by a lack of confidence in
      others to manage the condition. The study identifies the need for increased
      awareness of the condition, particularly in relation to emergency treatment.

PMID- 28516129
TI  - Enhanced Recovery After Colorectal Surgery (ERAS) in Elderly Patients Is Feasible
      and Achieves Similar Results as in Younger Patients.
AB  - Aim: Enhanced recovery after surgery (ERAS) is a multimodal approach that aims to
      optimize perioperative treatment. Whether elderly patients receiving colorectal
      surgery can adhere to and benefit from an ERAS approach is uncertain. The aim of
      this study was to compare patients in different age groups participating in an
      ERAS program. Method: In this substudy of a randomized controlled trial, we
      analyzed the interventional ERAS arm of adult patients eligible for laparoscopic
      or open colorectal resection with regard to the importance of age. Patients were
      divided into three groups based on age: <=65 years (n = 79), 66-79 years (n =
      56), and >=80 years (n = 19). The primary end point was total postoperative
      hospital stay (THS). Secondary end points were postoperative hospital stay,
      postoperative complications, postoperative C-reactive protein levels, readmission
      rate, mortality, and patient adherence to the different ERAS elements. All
      parameters and measuring the adherence to the ERAS protocol were recorded before
      surgery, on the day of the operation, and daily until discharge. Results: There
      were no significant differences in length of THS between age groups (<=65 years,
      median 5 [range 2-47] days; 66-79 years, median 5.5 [range 2-36] days; >=80
      years, median 7 [range 3-50] days; p = .53). All secondary outcomes were similar
      between age groups. Patient adherence to the ERAS protocol was as good in the
      elderly as it was in the younger patients. Conclusion: Elderly patients adhered
      to and benefited from an ERAS program, similar to their younger counterparts.

PMID- 28516130
TI  - Nutritional Status and Body Composition of Independently Living Older Adults in a
      Snowy Region of Japan.
AB  - Lifestyle diseases, which are associated with nutrition, account for 30% of
      elderly requiring long-term care. To increase health expectancy among Japan's
      rapidly aging population, we investigated the nutritional status and body
      composition of elderly adults living in a region subject to heavy snowfall, to
      identify pertinent health indicators. The dietary habits of 288 local residents
      aged >=50 years were analyzed using body composition and a brief-type self
      administered diet history questionnaire. Body mass index of all residents was
      normal. Basal metabolic rate (BMR) and muscle mass were reduced in the older
      group. Dietary habits did not differ with age among men, but older women had
      significantly higher dietary intake. BMR and muscle mass declined with age, even
      when dietary intake was sustained. Despite sufficient dietary intake,
      independently living older adults demonstrate less efficient use of food with
      age. Interventions to reduce excessive sodium and protein intake are required.

PMID- 28516131
TI  - The Cardiac Sympathetic Nerve Activity in the Elderly Is Attenuated in the Right
      Lateral Decubitus Position.
AB  - Objectives: The aim of this study was to evaluate the effect of the supine, left
      lateral decubitus, and right lateral decubitus positions on autonomic nervous
      activity in elderly adults by using spectral analysis of heart rate variability
      (HRV). Method: Forty-five adults aged 73.6 +/- 5.7 years were enrolled. After
      lying in the supine position, all participants moved to the lateral decubitus
      positions in a random order and maintained the positions for 10 min, while
      electrocardiographic data were recorded to measure HRV. Results: The lowest heart
      rate continued for 10 min when participants were in the left lateral decubitus
      position compared with the other two positions (p < .001), while the HRV indexes
      remained unchanged. The low-frequency HRV to high-frequency HRV ratio (LF/HF) for
      the right lateral decubitus position was significantly lower than that for the
      other positions. Discussion: The right lateral decubitus position may attenuate
      sympathetic nerve activity in elderly adults.

PMID- 28516133
TI  - Transcatheter arterial chemoembolization of hepatocellular carcinoma in patients
      with celiac axis occlusion using pancreaticoduodenal arcade as a challenging
      alternative route.
AB  - INTRODUCTION: Celiac axis occlusion is a challenging condition when
      catheterization of the hepatic artery is required for chemoembolization of
      hepatocellular carcinoma (HCC). As a result, the hepatic artery has to be
      catheterized through the pancreaticoduodenal arcades (PDA) and the gastroduodenal
      artery (GDA) from the superior mesenteric artery (SMA) which is a tortuous course
      with acute angles and small caliber branches. OBJECTIVE: To assess new techniques
      for facilitating catheterization of the tortuous PDA and the GDA to reach the
      proper hepatic artery (PHA) and tumor-feeding branches in patients with celiac
      axis occlusion undergoing chemoembolization of HCC. METHODS AND MATERIALS: The
      study included eleven patients all admitted to do transcatheter arterial
      chemoembolization (TACE) for treatment of unresectable HCC. During angiography
      occlusion of the celiac axis was diagnosed and hypertrophied PDA and GDA was
      noted in SMA angiography. Catheterization of the PDA was performed by preshaping
      of the micro-guide wire into a wide curve. Catheterization of the PHA was a
      challenge and was achieved by reshaping of the micro-guide wire or by looping
      technique. TACE was done after super selective catheterization of the tumor
      feeding artery using a mixture of 50 mg of adriamycin, 7cc of lipiodol and
      gelfoam. RESULTS: In the eleven patients with celiac artery occlusion, DSA showed
      complete celiac axis occlusion in all patients. Collateral arteries supplying the
      liver were readily evident via PDA and GDA from SMA. Successful catheterization
      of the PHA was achieved in all patients. Chemoembolization was performed to all
      patients after super selective catheterization of the feeding artery. Follow-up
      triphasic CT was performed in all patients, 9 patients showed good lipiodol
      trapping with no residual tumor enhancement. Two patients required another
      session of TACE. CONCLUSION: Chemoembolization of HCC through the PDA and the GDA
      using micro-guide wire preshaping technique and the microcatheter looping
      technique in patients with celiac axis occlusion is a challenging but effective
      treatment for HCC.

PMID- 28516132
TI  - Life-Threatening Hypercalcemia During Prodrome of Pneumocystis jiroveci Pneumonia
      in an Immunocompetent Infant.
AB  - Severe hypercalcemia in infants is usually attributed to genetic etiologies and
      less commonly to acquired ones. An 8-week-old girl presented with failure to
      thrive, mild respiratory distress, and life-threatening hypercalcemia (23.5
      mg/dL). Serum 1,25(OH)2-vitamin D (1,25(OH)2-D) level was elevated and
      parathyroid hormone undetectable. Evaluation for genetic mutations and malignant
      etiologies of hypercalcemia was negative. Treatment with intravenous hydration,
      loop diuretic, and calcitonin failed to correct the hypercalcemia, which was
      subsequently controlled with bisphosphonate therapy. Due to progressive
      respiratory deterioration, a bronchopulmonary lavage was done on day 17 of her
      hospitalization disclosing Pneumocystis jiroveci infection. The subsequent
      immunological investigation showed no abnormalities. She was treated with
      trimethoprim/sulfamethoxazole resulting in gradual clearing of her lungs and
      normalization of serum 1,25(OH)2-D level. A year later, she remains healthy with
      normal biochemical parameters of mineral metabolism. We conclude that in a child
      with hypercalcemia with suppressed parathyroid hormone and elevated 1,25(OH)2-D,
      once the genetic etiology for elevated 1,25(OH)2-D and malignancy are ruled out,
      one should investigate closely for a chronic granulomatous disease. Among the
      latter Pneumocystis jiroveci pneumonia infection should be considered even in an
      immunocompetent child.

PMID- 28516134
TI  - Data on metals biomonitoring in the body of schoolchildren in the vicinity of a
      heavily industrialized site.
AB  - This data is obtained from analyzing the concentration of metals include Al, Co,
      Cr, Cu, Fe, Mo, Pb, and Zn in the urine of schoolchildren in Asalouyeh city in
      vicinity to a heavily industrialized site and comparison with a reference city.
      The significance of sex groups on urine metal level was evaluated through this
      data. The urinary content of metals was measured by inductively coupled plasma
      atomic emission spectroscopy (ICP-OES). Statistical analyze of data were done by
      Mann-Whitney test. The herein presented date could beneficial for health
      assessment of gas and petrochemical companies.

PMID- 28516135
TI  - Data for the synthesis of resorcinol-formaldehyde aerogels in acidic and basic
      media.
AB  - The aim of this research is to synthesise carbon aerogels and to compare the
      differences in their textural, morphological and chemical properties when
      synthesised in basic and acidic media, and with two different types of
      pretreatment carbonization and activation with CO2. Four samples are prepared and
      characterised using TGA-DTA, SEM, DRX, isotherm determination of N2 adsorption
      desorption at -196  degrees C and immersion calorimetry. The data for pore
      distribution are reported using non-local density functional theory and quenched
      solid density functional theory. Finally, with the immersion calorimetry data,
      the consistency between the results using this technique and those obtained using
      the nitrogen isotherms is analysed.

PMID- 28516136
TI  - Primers and probe design and precision assessment of the real time RT-PCR assay
      in Coxsackievirus A10 and enterovirus detection.
AB  - This data article contains data related to the research article entitled "Rapid
      detection of enterovirus and Coxsackievirus A10 by a TaqMan based duplex one-step
      real time RT-PCR assay" (Chen at al., 2017) [1]. Primers and probe sequence
      design are among the most critical factors in real-time polymerase chain reaction
      (PCR) assay optimization. Linearity, sensitivity, specificity and precision are
      the crucial criteria which are used to evaluate the performance of a new method.
      This data article report the primers and probe design and precision assessment of
      the new assay. VP1 gene of Coxsackievirus A10 (CV-A10) and 5'-NCR of different
      enterovirus (EV) serotypes were retrieved from GenBank database and aligned. The
      intra- and inter-assay variation were assessed using high, medium and low
      concentration of control plasmid DNA and viral RNA samples.

PMID- 28516137
TI  - A curated dataset of complete Enterobacteriaceae plasmids compiled from the NCBI
      nucleotide database.
AB  - Thousands of plasmid sequences are now publicly available in the NCBI nucleotide
      database, but they are not reliably annotated to distinguish complete plasmids
      from plasmid fragments, such as gene or contig sequences; therefore, retrieving
      complete plasmids for downstream analyses is challenging. Here we present a
      curated dataset of complete bacterial plasmids from the clinically relevant
      Enterobacteriaceae family. The dataset was compiled from the NCBI nucleotide
      database using curation steps designed to exclude incomplete plasmid sequences,
      and chromosomal sequences misannotated as plasmids. Over 2000 complete plasmid
      sequences are included in the curated plasmid dataset. Protein sequences produced
      from translating each complete plasmid nucleotide sequence in all 6 frames are
      also provided. Further analysis and discussion of the dataset is presented in an
      accompanying research article: "Ordering the mob: insights into replicon and MOB
      typing..." (Orlek et al., 2017) [1]. The curated plasmid sequences are publicly
      available in the Figshare repository.

PMID- 28516138
TI  - Data on metabolic-dependent antioxidant response in the cardiovascular tissues of
      living zebrafish under stress conditions.
AB  - In this article we used transgenic zebrafish lines that express compartment
      specific isoforms of the roGFP2-Orp1 and Grx1-roGFP2 biosensors, described in
      Panieri et al (2017) [1], to test the contribute of the pentose phosphate pathway
      and of the glutathione biosynthesis in the antioxidant capacity of myocardial and
      endothelial cells in vivo. The transgenic zebrafish embryos were subdued to
      metabolic inhibition and subsequently challenged with H2O2 or the redox-cycling
      agent menadione to respectively mimic acute or chronic oxidative stress. Confocal
      time-lapse recordings were performed to follow the compartmentalized H2O2 and
      EGSH changes in the cardiovascular tissues of zebrafish embryos at 48 h post
      fertilization. After sequential excitation at 405 nm and 488 nm the emission was
      collected between 500-520 nm every 2 min for an overall duration of 60 min. The
      405/488 nm ratio was normalized to the initial value obtained before oxidants
      addition and plotted over time. The analysis and the interpretation of the data
      can be found in the associated article [1].

PMID- 28516139
TI  - Dataset of two experiments of the application of gamified peer assessment model
      into online learning environment MeuTutor.
AB  - In this dataset, we present the collected data of two experiments with the
      application of the gamified peer assessment model into online learning
      environment MeuTutor to allow the comparison of the obtained results with others
      proposed models. MeuTutor is an intelligent tutoring system aims to monitor the
      learning of the students in a personalized way, ensuring quality education and
      improving the performance of its members (Tenorio et al., 2016) [1]. The first
      experiment evaluated the effectiveness of the peer assessment model through
      metrics as final grade (result), time to correct the activities and associated
      costs. The second experiment evaluated the gamification influence into peer
      assessment model, analyzing metrics as access number (logins), number of
      performed activities and number of performed corrections. In this article, we
      present in table form for each metric: the raw data of each treatment; the
      summarized data; the application results of the normality test Shapiro-Wilk; the
      application results of the statistical tests T-Test and/or Wilcoxon. The
      presented data in this article are related to the article entitled "A gamified
      peer assessment model for on-line learning environments in a competitive context"
      (Tenorio et al., 2016) [1].

PMID- 28516140
TI  - Comprehensive list of metabolites measured by DI-FTICR mass spectrometry in thyme
      plants with contrasting tolerance to drought.
AB  - This article contains data related to the main research entitled "Metabolomic
      approach reveals the biochemical mechanisms underlying drought stress tolerance
      in Thyme" (Moradi et al., 2017) [1]. Two thyme populations with contrasting
      drought tolerance were subjected to long term water deficit. Leaf samples
      harvested at the end of stress period and bi-phasic extraction carried out to get
      polar and non-polar fractions. Extracted samples were analyzed through Direct
      Infusion FT-ICR mass spectrometry. Date files comprise of four separate tables
      for all the putatively identified metabolites and their intensities in watered
      and droughted plants. P-values beside each m/z values indicate significances of
      difference between peak intensities of stressed and control conditions.

PMID- 28516141
TI  - WST-assay data reveal a pH dependence of the mitochondrial succinate reductase in
      osteoblast-like cells.
AB  - The data presented in this article are related to the research article entitled
      "Increased osteoblast viability at alkaline pH in vitro provides a new
      perspective on bone regeneration" (doi: 10.1016/j.bbrep.2017.02.001; (Galow et
      al., 2017) [1]). The water soluble tetrazolium (WST) proliferation assay detects
      the metabolic activity of the respiratory chain of cultured cells. The assay is
      based on changes in the light absorbance resulting from the metabolism of WST-1
      into formazane by mitochondrial succinate reductase. We present data of three
      different tests that were carried out to check whether WST assay readouts are pH
      dependent. In a first test, a possible pH effect on the photometric measurements,
      for example by shifting the absorbance spectrum of the pH indicator of the cell
      culture medium, was excluded. Because the second test revealed a significant pH
      dependence of the activity of the mitochondrial succinate reductase, a third long
      term test was conducted to analyze possible changes of the pH dependence over
      time. The higher absorbance per one million cells at alkaline pH, which was
      approximately four-fold at pH 8.4 compared to the pH-7.4 reference on day one
      decayed gradually, with the pH-differences equilibrating over six days.

PMID- 28516142
TI  - Survey data on factors affecting negotiation of professional fees between Estate
      Valuers and their clients when the mortgage is financed by bank loan: A case
      study of mortgage valuations in Ikeja, Lagos State, Nigeria.
AB  - In this article, two sets of questionnaires were administered to professionals
      and clients (commercial banks) on their willingness to negotiate the professional
      fees charged by the Estate Valuers assuming that the mortgage in valuation was
      financed by bank loan. A range of fees options were provided. Other factors such
      as the business environment and mortgage valuation can influence the negotiated
      fees when the data obtained from the survey data is analyzed.

PMID- 28516143
TI  - Change-point analysis data of neonatal diffusion tensor MRI in preterm and term
      born infants.
AB  - The data presented in this article are related to the research article entitled
      "Mapping the Critical Gestational Age at Birth that Alters Brain Development in
      Preterm-born Infants using Multi-Modal MRI" (Wu et al., 2017) [1]. Brain
      immaturity at birth poses critical neurological risks in the preterm-born
      infants. We used a novel change-point model to analyze the critical gestational
      age at birth (GAB) that could affect postnatal development, based on diffusion
      tensor MRI (DTI) acquired from 43 preterm and 43 term-born infants in 126 brain
      regions. In the corresponding research article, we presented change-point
      analysis of fractional anisotropy (FA) and mean diffusivities (MD) measurements
      in these infants. In this article, we offered the relative changes of axonal and
      radial diffusivities (AD and RD) in relation to the change of FA and FA-based
      change-points, and we also provided the AD- and RD-based change-point results.

PMID- 28516144
TI  - Geospatial datasets in support of high-resolution spatial assessment of
      population vulnerability to climate change in Nepal.
AB  - We present a geographic information system (GIS) dataset with a nominal spatial
      resolution of one-kilometer composed of grid polygons originally derived and
      utilized in a high-resolution climate vulnerability model for Nepal. The
      different data sets described and shared in this article are processed and
      tailored to the specific objectives of our research paper entitled "High
      resolution Spatial Assessment of Population Vulnerability to Climate Change in
      Nepal" (Mainali and Pricope, In press) [1]. We share these data recognizing that
      there is a significant gap in regards to data availability, the spatial patterns
      of different biophysical and socioeconomic variables, and the overall population
      vulnerability to climatic variability and disasters in Nepal. Individual
      variables, as well as the entire set presented in this dataset, can be used to
      better understand the spatial pattern of different physical, biological,
      climatic, and vulnerability characteristics in Nepal. The datasets presented in
      this article are sourced from different national and global databases and have
      been statistically treated to meet the needs of the article. The data are in GIS
      ready ESRI shapefile file format of one-kilometer grid polygon with various
      fields (columns) for each dataset.

PMID- 28516145
TI  - Zinc, nickel, and cobalt ions removal from aqueous solution and plating plant
      wastewater by modified Aspergillus flavus biomass: A dataset.
AB  - The biomass of Aspergillus flavus was modified by calcium chloride to achieve a
      bioadsorbent for treating nickel, cobalt, and zinc ions from aqueous solutions.
      The information of pH, bioadsorbent dose, contact time, and temperature effect on
      the removal efficiency are presented. The data of Freundlich and Langmuir
      isotherm and pseudo-first-order and pseudo-second-order kinetic models are also
      depicted. The data showed that the maximum bioadsorption capacity of nickel,
      cobalt, and zinc ions is 32.26, 31.06 and 27.86 mg/g, respectively. The
      suitability of the bioadsorbent in heavy metals removal at field condition was
      tested with a real wastewater sample collected from a plating plant in the final
      part of this dataset. Based on the findings, the bioadsorbent was shown to be an
      affordable alternative for the removal of metals in the wastewater.

PMID- 28516146
TI  - Interactive effects of gallic/ferulic/caffeic acids and anthocyanins on pigment
      thermal stabilities.
AB  - The data presented in this article are related to the research article entitled
      "The effects of gallic/ferulic/caffeic acids on colour intensification and
      anthocyanin stability" (Qian et al., 2017) [1]. This paper described preparation
      and isolation of anthocyanins from purple sweet potatoes (PSP) and the time
      course of anthocyanin profiles treated with gallic, ferulic, or caffeic acids at
      95  degrees C. The color appearance of PSPanthocyanins alone, or with gallic,
      ferulic, or caffeic acids was described after the 15 h of thermal treatment. The
      high resolution mass spectrographs of PSP anthocyanins were determined using UPLC
      ESI-HRMS. The spatial interaction of peonidin 3-O-(2-O-beta-D-glucopyranocyl-beta
      D-glucopyranoide)-5-O-beta-D-glucopyranoside and gallic/ferulic/caffeic acids was
      illustrated by molecular dynamic simulation.

PMID- 28516147
TI  - Buyer and seller data from pay what you want and name your own price laboratory
      markets.
AB  - Pay What You Want (PWYW) and Name Your Own Price (NYOP) are customer-driven
      pricing mechanisms that give customers (some) pricing power and that have been
      used in service industries with high fixed costs to price discriminate without
      setting a reference price. This paper describes buyer and seller data in a series
      of induced-value laboratory experiments that compare PWYW and NYOP in monopoly
      and competitive situations. Sellers are in a one-shot interaction with buyers.
      Sellers using customer-driven pricing mechanisms may exogenously or endogenously
      receive additional promotional benefits, for instance through word-of-mouth
      effects. The major findings based on the data presented here are reported in the
      paper "Delegating Pricing Power to Customers: Pay What You Want or Name Your Own
      Price?" (Kramer et al., 2017) [3].

PMID- 28516148
TI  - Data of the Modified Somatic Perception Questionnaire (MSPQ) administered to a
      sample of immigrants in Genoa (Italy).
AB  - This article reports the data of the Modified Somatic Perception Questionnaire
      (MSPQ) administered to a sample of 143 immigrants accessing an outpatient clinic
      or the general practitioners offices in Genoa (Italy) compared with 186 Italian
      patients. For further details and for the interpretation of the data, the reader
      is referred to the original publication "Somatic perception, cultural differences
      and immigration: results from administration of the Modified Somatic Perception
      Questionnaire (MSPQ) to a sample of immigrants" by Bragazzi et al. (2014) [1].

PMID- 28516149
TI  - Dataset for acrylate/silica nanoparticles formulations and photocured composites:
      Viscosity, filler dispersion and bulk Poisson's ratio.
AB  - UV-curable polymer composites are of importance in industry, biomedical
      applications, scientific fields, and daily life. Outstanding physical properties
      of polymer composites were achieved with nanoparticles as filler, primarily in
      enhancing mechanical strength or barrier properties. Structure-property
      relationships of the resulting nanocomposites are dictated by the polymer-filler
      molecular architecture, i.e. interactions between polymer matrix and filler, and
      high surface area to volume ratio of the filler particles. Among monomers,
      acrylates and methacrylates attracted wide attention due to their ease of
      polymerization and excellent physicochemical and mechanical properties of the
      derived polymers. We prepared and photopolymerized two series of formulations
      containing hydrophobized silica nanofiller (Aerosil R7200) dispersed in 2
      hydroxyethyl acrylate (HEA) or polyethylene glycol diacrylate (PEGDA) monomers.
      We compared selected physical properties of the formulations, both before and
      after photocuring; specifically the viscosity of formulations and dispersion of
      the filler in the polymer matrices. Additionally, we estimated the bulk Poisson's
      ratio of the investigated nanocomposites. This article contains data related to
      the research article entitled "Nanoscale Young's modulus and surface morphology
      in photocurable polyacrylate/nanosilica composites" (Gojzewski et al., 2017) [1].

PMID- 28516150
TI  - Proteome dataset of subcutaneous adipose tissue obtained from late pregnant dairy
      cows during summer heat stress and winter seasons.
AB  - Adipose tissue has a central role in the regulation of metabolism in dairy cows,
      and many proteins expressed in this tissue are involved in metabolic responses to
      stress (Peinado et al., 2012) [1]. Environmental heat stress is one of the main
      stressors limiting production in dairy cattle (Fuquay, 1981; West, 2003) [2],
      [3], and there is a complex interaction between heat stress and the transition
      period from late pregnancy to onset of lactation, which is manifested in heat
      stressed late-gestation cows (Tao and Dahl, 2013) [4]. We recently defined the
      proteome of adipose tissue in peripartum dairy cows, identifying 586 proteins of
      which 18.9% were differentially abundant in insulin-resistant compared to insulin
      sensitive adipose tissue (Zachut, 2015) [5]. That study showed that proteomic
      techniques constitute a valuable tool for identifying novel biomarkers in adipose
      tissue that are related to metabolic adaptation to stress in dairy cows. The
      objective of the present work was to examine the adipose tissue proteome under
      thermo-neutral or seasonal heat stress conditions in late pregnant dairy cows. We
      have collected subcutaneous adipose tissue biopsies from 10 late pregnant dairy
      cows during summer heat stress and from 8 late pregnant dairy cows during winter
      season, and identified and quantified 1495 proteins in the adipose tissues. This
      dataset of adipose tissue proteome from dairy cows adds novel information on the
      variety of proteins that are abundant in this tissue during late pregnancy under
      thermo-neutral as well as heat stress conditions. Differential abundance of 107
      (7.1%) proteins was found between summer and winter adipose. These results are
      discussed in our recent research article (Zachut et al., 2017) [6].

PMID- 28516151
TI  - Transport, mechanical and global migration data of multilayer copolyamide
      nanocomposite films with different layouts.
AB  - Transport, mechanical and global migration data concern multilayer food packaging
      films with different layouts, all incorporating a layered silicate/polyamide
      nanocomposite as oxygen barrier layer, and a low-density polyethylene (LDPE) as
      moisture resistant layer in direct contact with food. The data are related to
      "Tuning of co-extrusion processing conditions and film layout to optimize the
      performances of PA/PE multilayer nanocomposite films for food packaging" by
      Garofalo et al. (2017) [1]. Nanocomposite multilayer films, with different
      relative layer thicknesses and clay types, were produced using a laboratory scale
      co-extrusion blown-film equipment and were analyzed in terms of transport to
      oxygen and water vapor, mechanical properties and overall migration. The results
      have shown that all the multilayer hybrid films, based on the copolyamide layer
      filled with Cloisite 30B, displayed the most significant oxygen barrier
      improvements and the best mechanical properties compared to the unfilled films.
      No significant alteration of the overall migration values was observed, as
      expectable [2], [3], [4]. The performance improvement was more relevant in the
      case of the film with the thinner nanocomposite layer.

PMID- 28516153
TI  - Neutrophil to Lymphocyte Ratio (NLR) at the Time of Transurethral Resection of
      Bladder Tumor: A Large Retrospective Study and Analysis of Racial Differences.
AB  - Introduction: Neutrophil/lymphocyte ratio (NLR) is an indicator of systemic
      inflammation and has been proven to be associated with an increased risk of
      extravesical disease, decreased cancer specific survival and overall survival in
      bladder cancer patients. A large proportion of healthy African Americans have a
      WBC count that is persistently lower than the normal range defined for
      individuals of European ancestry, this condition has been called "benign ethnic
      neutropenia". The purpose of our study was to determine if NLR was different in
      patients of African ancestry (AA) vs European ancestry (EA) across different
      tumor grades and stages at the time of transurethral resection of bladder
      tumor(s) (TURBT). Materials and Methods: The records of consecutive patients who
      underwent TURBT were reviewed from the University of Wisconsin and the Atlanta
      Veterans' Administration Medical Center (2000-2012). NLR was compared across
      tumor stage, tumor grade and ethnicity. Results: 297 consecutive patients met
      study criteria. 89% and 86%, were males and of European ancestry (EA)
      respectively. NLRs were different across T-stages (Ta-2.5, T1-3.9, T2-3.8; p =
      0.001). but not across tumor grades in Ta (LG-2.5 vs HG-3.9, p = 0.57). EA had
      higher NLRs than AA (3.4 vs 1.9; p < 0.001). Conclusions: Higher NLRs appear to
      be associated with more advanced tumor stage at the time of TURBT. Patients of
      African ancestry have lower NLRs across all tumor stages compared to patients of
      European ancestry. Ethnicity should be taken into account when interpreting the
      NLR in patients with bladder cancer.

PMID- 28516152
TI  - CDK4/6 Inhibitors in Cancer Therapy: A Novel Treatement Strategy for Bladder
      Cancer.
AB  - Patients with metastatic bladder cancer (mBC) treated with cisplatin-based
      chemotherapy have a limited median survival of only around 14 months [1]. Despite
      over 30 years of basic and clinical research, until recently no therapeutic
      options beyond cisplatin-based therapy had entered clinical routine and, at least
      in the US, none of the tested agents had been approved for second-line treatment.
      This has changed with the advent of immune checkpoint blockade, including
      especially PD-1/PD-L1 inhibitors. The high response rates of 24% over a 14.4
      month follow up led to the first US Food and Drug Administration (FDA) approval
      for a second line therapy for these patients, and it is likely that this marks
      the beginning of a new era in the systemic treatment of muscle-invasive bladder
      cancer [2-4]. The strong clinical need to improve the medical management of this
      disease for those patients, not responding to current therapy has led to an
      increased molecular understanding of bladder cancer and has forstered the
      development of many potential molecular manipulations and targeted strategies
      beyond the new immune-oncologic approaches. Among the molecular alterations
      indentified in bladder cancer, cell cycle deregulation appears to be a key driver
      of disease progression. Target-directed therapy against CDK4/6 is an emerging
      strategy to regain control of cell cycle deregulation. Here, we provide an
      overview of the current status of CDK4/6 inhibitors in cancer therapy, their
      potential use in mBC and the challenges for their clinical use.

PMID- 28516154
TI  - WBC Associates with Readmission Following Cystectomy.
AB  - Background: Radical cystectomy is associated with perioperative complication
      rates exceeding 50% in some series. Readmission rates are increasingly used as a
      surgical quality metric. White blood cell count is a crude surrogate for
      physiologic processes which may reflect postoperative complications leading to
      readmission. Objective: We assessed the association between final white blood
      cell count at discharge and risk of readmission following radical cystectomy.
      Methods: Records on 477 patients undergoing radical cystectomy from 2006-2013
      were reviewed. Final white blood cell count was defined as the last documented
      value during index admission. Univariate analysis was performed using Fisher's
      exact, Wilcoxon rank sum test, and Spearman's coefficient tests where
      appropriate. Multivariable logistic regression models were used to test the
      associations between final white blood cell count and readmission. Results: 34%
      of patients were readmitted within 90 days of surgery. Amongst this cohort, a
      cutoff final white blood cell count of 9000/mm3 was identified, with a
      significantly higher proportion of patients with values >9000/mm3 experiencing
      readmission than those with values<=9000/mm3 (42% vs 28%, p = 0.004). Other
      perioperative variables associated with an increased readmission rate included
      initial hospital length of stay<=10 days, and receipt of a continent diversion.
      Following adjustment, final white blood cell count >9000/mm3 was associated with
      increased risk of readmission (OR 2.09, 95% CI 1.23-3.53, p = 0.006).
      Conclusions: Final white blood cell count is associated with hospital readmission
      following radical cystectomy. This metric may provide important guidance in
      discharge algorithms.

PMID- 28516155
TI  - Phase I Clinical Trial of Everolimus Combined with Trimodality Therapy in
      Patients with Muscle-Invasive Bladder Cancer.
AB  - Background: Local control following trimodality therapy (TMT) for muscle-invasive
      bladder cancer (MIBC) requires further optimization. Objective: Evaluating the
      biologic endpoint, feasibility, and toxicity of integrating everolimus to TMT in
      patients with MIBC. Methods: This was a phase I trial in patients with MIBC who
      were not surgical candidates or who refused cystectomy. Following maximal
      transurethral tumor resection, patients were treated by radiotherapy (50 Gy/20
      fractions), gemcitabine (100 mg/m2/weekly) and escalating doses of everolimus
      (2.5-5.0 mg/day). Everolimus was given daily for one month prior to radiation,
      during treatment, and one month post-radiation. Toxicity assessment followed the
      Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria.
      Biologic endpoint with downregulation of phospho-S6 (pS6) was assessed using
      immunohistochemistry. Local response was evaluated with imaging and bladder
      biopsy post-therapy. Results: 10 patients were recruited; 8 males, 2 females.
      Median age was 78 years (range: 63-85). Four patients entered everolimus 2.5 mg
      cohort. Six other patients entered everolimus 5.0 mg cohort. Toxicities were
      encountered in 2 patients (Grade I), 6 patients (Grade II), 9 patients (Grade
      III) and 1 patient (Grade IV), with some experiencing more than one toxicity.
      Most Grade III and IV toxicities were encountered from everolimus alone prior to
      combination testing. Trial was terminated early due to toxicity. Interestingly,
      6/10 patients (60%) achieved a complete response with negative post-treatment
      biopsies. Significant decrease of pS6 was demonstrated post-therapy (p = 0.03).
      Conclusions: Although combining everolimus with TMT achieved a biological
      endpoint and complete response in a significant number of patients with MIBC and
      negative prognostic factors, it was associated with unacceptable increased
      toxicity.

PMID- 28516156
TI  - Single Arm Phase I/II Study of Everolimus and Intravesical Gemcitabine in
      Patients with Primary or Secondary Carcinoma In Situ of the Bladder who failed
      Bacillus Calmette Guerin (NCT01259063).
AB  - Background: Standard treatment for BCG-refractory urothelial cancer is radical
      cystectomy. Identification of active agents is clearly warranted. Objective: To
      determine a safe dose of oral everolimus in combination with standard
      intravesical gemcitabine and to evaluate the efficacy of this combination.
      Methods: Patients with carcinoma in situ refractory to intravesical bacillus
      Calmette-Guerin and refusing cystectomy were eligible. Patients in the phase I
      part of the trial received one of three dose levels of oral everolimus. Patients
      also received a fixed dose of intravesical gemcitabine. Maintenance everolimus
      was given for 12 months in patients achieving a complete response confirmed by
      cystoscopy and cytology. Patients in phase II received continuous everolimus
      administered at 10 mg daily with intravesical gemcitabine followed by everolimus
      maintenance for 12 months of total therapy. The enrollment goal for the phase II
      was 33 patients. Results: 14 patients were enrolled in phase I of the trial. 23
      patients were enrolled in phase II of the trial and 19 were evaluable for primary
      and secondary endpoints. Four patients withdrew consent prior to treatment
      initiation. Of the 19 patients evaluable for response, 3 (16%, 95% confidence
      interval [CI] 3% - 40%) were disease free at 1 yr. The probability of RFS was 20%
      (95% CI 5% - 42%) at 12 months. Ten patients out of 19 had grade 3 or greater
      toxicity events. Seven withdrew consent or were taken off study. Conclusions:
      Many patients withdrew, and enrollment was halted. Continuous oral everolimus
      plus intravesical gemcitabine was not well tolerated in this patient population
      where the threshold for tolerability is low.

PMID- 28516158
TI  - A Management Algorithm for Mitomycin C Induced Cystitis.
AB  - Background/Objective: A post-bladder tumor resection dose of MMC can reduce non
      invasive papillary (pTa) bladder cancer recurrences by up to 40%; this treatment
      is recommended in both the AUA and EUA non-muscle-invasive bladder cancer
      guidelines. A common complication of this treatment is eosinophilic cystitis.
      Symptoms range from mild urinary frequency and urgency to debilitating pain and
      dysuria. Currently, there is no established treatment algorithm for MMC-induced
      cystitis. Methods: Members of the Urologic Surgery Quality Collaborative (USQC),
      a group composed of over 160 private and academic urologists, met to discuss the
      management of patients with cystitis following MMC therapy. They devised a
      treatment algorithm based on experiences of urologic oncologists and
      neurourologists to aid in the diagnosis and management of MMC-induced cystitis.
      Results: The assessment begins with urinalysis and culture, followed by
      cystoscopy. For mild symptoms, behavioral therapy, including timed voids, fluid
      restriction and Kegel exercises are trialed. If symptoms have not resolved,
      treatment with an antihistamine, followed by a combination of anticholinergic and
      alpha-blocker medications. For persistent symptoms or severe symptoms at
      presentation, a course of prednisone plus antihistamine is prescribed. If
      symptoms are improving but have not resolved, this treatment is extended for a
      full 4 weeks prior to steroid taper. If symptoms do not improve, any visible
      bladder ulcerations are resected intraoperatively followed by an additional
      course of prednisone and antihistamine. Intravesical DMSO instillations and intra
      ulcer steroid injection can be used as a final effort to treat this condition.
      Conclusion: We present the first formal management algorithm with escalating
      treatment intensity tailored to patient symptoms.

PMID- 28516157
TI  - Survival after Metastasectomy for Metastatic Urothelial Carcinoma: A Systematic
      Review and Meta-Analysis.
AB  - Background: Cisplatin-based combination chemotherapy is standard treatment for
      metastatic urothelial carcinoma; however, the vast majority of patients
      experience disease progression. As systemic therapy alone is rarely curative for
      the treatment of metastatic urothelial cancer, not only are new therapies needed
      but also refinement of general treatment principles. Herein, we conducted a
      systematic review and meta-analysis to explore the role of metastasectomy in
      metastatic urothelial carcinoma. Methods: We conducted a systematic review of the
      literature regarding local treatment for metastatic urothelial carcinoma. An
      online electronic search of the PubMed/MEDLINE and EMBASE databases was performed
      to identify peer-reviewed articles. All procedures were performed according to
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. Information was then extracted including number of patients, gender,
      the site of the primary urothelial tumor, site of metastasis, chemotherapy before
      or after metastasectomy, overall survival (OS), and disease specific survival
      (DSS) after metastasectomy. A meta-analysis was performed with those studies with
      sufficient survival data to obtain pooled overall survival. The article quality
      was assessed using the Cochrane Handbook "risk of bias" tool. Results: Seventeen
      out of 3963 articles were eligible for review between 1990-2015, including a
      total of 412 patients. The mean time to recurrence after metastasectomy was 14.25
      months. The overall survival from time of metastasectomy ranged from 2 to 60
      months. Pooled analyses of studies reported survival data revealed an improved
      overall survival for patients treated with metastasectomy compared with non
      surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49-0.81). All,
      except for three studies, were retrospective and non-randomized, leading to a
      high risk of bias associated with patient selection, patient attrition, and
      reporting. Such high potential of selection bias may lead to higher OS than
      expected. Additionally, treatment and outcome details reported across studies was
      highly variable. Conclusions: Limited conclusions can be drawn from the available
      literature exploring the role of metastasectomy in the management of metastatic
      urothelial cancer due to lack of uniform reporting elements and multiple sources
      of bias particularly related to a lack of prospective randomized trials. As a
      subset of patients treated with metastasectomy achieve durable disease control,
      this approach may be considered for select patients.

PMID- 28516159
TI  - Challenging Cases in Urothelial Cancer.

PMID- 28516160
TI  - Clinical Trials Corner.

PMID- 28516161
TI  - Biallelic TOR1A variants in an infant with severe arthrogryposis.

PMID- 28516162
TI  - Recognizing Academic Performance, Sleep Quality, Stress Level, and Mental Health
      using Personality Traits, Wearable Sensors and Mobile Phones.
AB  - What can wearable sensors and usage of smart phones tell us about academic
      performance, self-reported sleep quality, stress and mental health condition? To
      answer this question, we collected extensive subjective and objective data using
      mobile phones, surveys, and wearable sensors worn day and night from 66
      participants, for 30 days each, totaling 1,980 days of data. We analyzed daily
      and monthly behavioral and physiological patterns and identified factors that
      affect academic performance (GPA), Pittsburg Sleep Quality Index (PSQI) score,
      perceived stress scale (PSS), and mental health composite score (MCS) from SF-12,
      using these month-long data. We also examined how accurately the collected data
      classified the participants into groups of high/low GPA, good/poor sleep quality,
      high/low self-reported stress, high/low MCS using feature selection and machine
      learning techniques. We found associations among PSQI, PSS, MCS, and GPA and
      personality types. Classification accuracies using the objective data from
      wearable sensors and mobile phones ranged from 67-92%.

PMID- 28516164
TI  - Engineered ligand-based VEGFR antagonists with increased receptor binding
      affinity more effectively inhibit angiogenesis.
AB  - Pathologic angiogenesis is mediated by the coordinated action of the vascular
      endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2
      (VEGFR2) signaling axis, along with crosstalk contributed by other receptors,
      notably alphavbeta3 integrin. We build on earlier work demonstrating that point
      mutations can be introduced into the homodimeric VEGF ligand to convert it into
      an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor
      has limited potency, however, due to loss of avidity effects from bivalent VEGFR2
      binding. Here, we used yeast surface display to engineer a variant with VEGFR2
      binding affinity approximately 40-fold higher than the parental antagonist, and
      14-fold higher than the natural bivalent VEGF ligand. Increased VEGFR2 binding
      affinity correlated with the ability to more effectively inhibit VEGF-mediated
      signaling, both in vitro and in vivo, as measured using VEGFR2 phosphorylation
      and Matrigel implantation assays. High affinity mutations found in this variant
      were then incorporated into a dual-specific antagonist that we previously
      designed to simultaneously bind to and inhibit VEGFR2 and alphavbeta3 integrin.
      The resulting dual-specific protein bound to human and murine endothelial cells
      with relative affinities of 120 +/- 10 pM and 360 +/- 50 pM, respectively, which
      is at least 30-fold tighter than wild-type VEGF (3.8 +/- 0.5 nM). Finally, we
      demonstrated that this engineered high-affinity dual-specific protein could
      inhibit angiogenesis in a murine corneal neovascularization model. Taken
      together, these data indicate that protein engineering strategies can be combined
      to generate unique antiangiogenic candidates for further clinical development.

PMID- 28516163
TI  - Engineered heparins as new anticoagulant drugs.
AB  - Heparin is an anionic polysaccharide that is widely used as a clinical
      anticoagulant. This glycosaminoglycan is prepared from animal tissues in metric
      ton quantities. Animal-sourced heparin is also widely used in the preparation of
      low molecular weight heparins that are gaining in popularity as a result of their
      improved pharmacological properties. The recent contamination of pharmaceutical
      heparin together with concerns about increasing demand for this life saving drug
      and the fragility of the heparin supply chain has led the scientific community to
      consider other potential sources for heparin. This review examines progress
      toward the preparation of engineered heparins through chemical synthesis,
      chemoenzymatic synthesis, and metabolic engineering.

PMID- 28516165
TI  - Host- and pathogen-derived adjuvant coatings on protein nanoparticle vaccines.
AB  - Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing
      immune responses, and the immunogenic vaccines of the future will most likely
      contain both. To investigate the immunostimulatory effects of molecular adjuvants
      on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles
      coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM).
      These proteins, derived from Salmonella and mice, respectively, are
      representatives of pathogen- and host-derived molecules that can enhance immune
      responses. FliC-coated OVA nanoparticles, soluble FliC (sFliC) admixed with OVA
      nanoparticles, IgM-coated nanoparticles, and OVA-coated nanoparticles were
      assessed for immunogenicity in an in vivo mouse immunization study. IgM coatings
      on nanoparticles significantly enhanced both antibody and T cell responses, and
      promoted IgG2a class switching but not affinity maturation. FliC-coated
      nanoparticles and FliC-admixed with nanoparticles both triggered IgG2a class
      switching, but only FliC-coated nanoparticles enhanced antibody affinity
      maturation. Our findings that affinity maturation and class switching can be
      directed independently of one another suggest that adjuvant coatings on
      nanoparticles can be tailored to generate specific vaccine effector responses
      against different classes of pathogens.

PMID- 28516166
TI  - Onset and remodeling of coronal imbalance after selective posterior thoracic
      fusion for Lenke 1C and 2C adolescent idiopathic scoliosis (a pilot study).
AB  - BACKGROUND: Postoperative coronal imbalance is a significant problem after
      selective thoracic fusion for primary thoracic and compensatory lumbar curves in
      adolescent idiopathic scoliosis (AIS). However, longitudinal studies on
      postoperative behavior of coronal balance are lacking. This multicenter
      retrospective study was conducted to analyze factors related to onset and
      remodeling of postoperative coronal imbalance after posterior thoracic fusion for
      Lenke 1C and 2C AIS. METHODS: Twenty-one Lenke 1C or 2C AIS patients, who
      underwent posterior thoracic fusion ending at L3 or above, were included with a
      minimum 2-year follow-up. The mean patients' age was 15.1 years at the time of
      surgery. Radiographic measurements were performed on Cobb angles of the main
      thoracic (MT) and thoracolumbar/lumbar (TLL) curves and coronal balance. Factors
      related to the onset of immediately postoperative coronal decompensation (IPCD)
      and postoperative coronal balance remodeling (PCBR), defined as an improvement of
      coronal balance during postoperative follow-up, were investigated using
      comparative and correlation analyses. RESULTS: Mean Cobb angles for the MT and
      TLL curves were 57.3 degrees  and 42.3 degrees  preoperatively and were corrected
      to 22.8 degrees  and 22.5 degrees  at final follow-up, respectively. Mean
      preoperative coronal balance of -3.8 mm got worse to -21.2 mm postoperatively,
      and regained to -12.0 mm at final follow-up. Coronal decompensation was observed
      in two patients preoperatively, in ten patients immediately postoperatively, and
      in three patients at final follow-up. The preoperative coronal balance and lowest
      instrumented vertebra (LIV) selection relative to stable vertebra (SV) were
      significantly different between patients with IPCD and those without. PCBR had
      significantly negative correlation with immediately postoperative coronal
      balance. CONCLUSIONS: IPCD after posterior thoracic fusion for Lenke 1C and 2C
      AIS was frequent and associated with preoperative coronal balance and LIV
      selection. However, most patients with IPCD regained coronal balance through
      PCBR, which was significantly associated with immediately postoperative coronal
      balance. A fixation more distal to SV shifted the coronal balance further to the
      left postoperatively.

PMID- 28516167
TI  - Standardization of the modified Rodnan skin score for use in clinical trials of
      systemic sclerosis.
AB  - The modified Rodnan skin score (mRSS) is a measure of skin thickness and is used
      as a primary or secondary outcome measure in clinical trials of systemic
      sclerosis (scleroderma). This state-of-art review provides a historical
      perspective of the development of the mRSS, summarizes the performance of mRSS as
      an outcome measure, provides guidance on assessing mRSS, and makes
      recommendations for incorporation of the mRSS into clinical trials.

PMID- 28516170
TI  - Mott physics beyond Brinkman-Rice scenario.
AB  - The main flaw of the well-known Brinkman-Rice description, obtained through the
      Gutzwiller approximation, of the paramagnetic Mott transition in the Hubbard
      model is in neglecting high-energy virtual processes that generate for instance
      the antiferromagnetic exchange J ~ t2/U. Here we propose a way to capture those
      processes by combining the Brinkman-Rice approach with a variational Schrieffer
      Wolff transformation, and apply this method to study the single-band metal-to
      insulator transition in a Bethe lattice with infinite coordination number, where
      the Gutzwiller approximation becomes exact. We indeed find for the Mott
      transition a description very close to the real one provided by dynamical mean
      field theory; an encouraging result in view of possible applications to more
      involved models.

PMID- 28516169
TI  - Hybrid Pixel-Waveform (HPWF) Enabled CdTe Detectors for Small Animal Gamma-Ray
      Imaging Applications.
AB  - This paper presents the design and preliminary evaluation of small-pixel CdTe
      gamma ray detectors equipped with a hybrid pixel-waveform (HPWF) readout system
      for gamma ray imaging applications with additional discussion on CZT due to its
      similarity. The HPWF readout system utilizes a pixelated anode readout circuitry
      which is designed to only provide the pixel address. This readout circuitry works
      in coincidence with a high-speed digitizer to sample the cathode waveform which
      provides the energy, timing, and depth-of-interaction (DOI) information. This
      work focuses on the developed and experimentally evaluated prototype HPWF-CdTe
      detectors with a custom CMOS pixel-ASIC to readout small anode pixels of 350 MUm
      in size, and a discrete waveform sampling circuitry to digitize the signal
      waveform induced on the large cathode. The intrinsic timing, energy, and spatial
      resolution were experimentally evaluated in this paper in conjunction with
      methods for depth of interaction (DOI) partitioning of the CdTe crystal. While
      the experimental studies discussed in this paper are primarily for evaluating
      HPWF detectors for small animal PET imaging, these detectors could find their
      applications for ultrahigh-resolution SPECT and other imaging modalities.

PMID- 28516168
TI  - Selective Surface PEGylation of UiO-66 Nanoparticles for Enhanced Stability, Cell
      Uptake, and pH-Responsive Drug Delivery.
AB  - The high storage capacities and excellent biocompatibilities of metal-organic
      frameworks (MOFs) have made them emerging candidates as drug-delivery vectors.
      Incorporation of surface functionality is a route to enhanced properties, and
      here we report on a surface-modification procedure-click modulation-that controls
      their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1)
      synthesized as ~200 nm nanoparticles coated with functionalized modulators, (2)
      loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol)
      (PEG) chains through mild bioconjugate reactions. At pH 7.4, the PEG chains endow
      the MOF with enhanced stability toward phosphates and overcome the "burst
      release" phenomenon by blocking interaction with the exterior of the
      nanoparticles, whereas at pH 5.5, stimuli-responsive drug release is achieved.
      The mode of cellular internalization is also tuned by nanoparticle surface
      chemistry, such that PEGylated UiO-66 potentially escapes lysosomal degradation
      through enhanced caveolae-mediated uptake. This makes it a highly promising
      vector, as demonstrated for dichloroacetic-acid-loaded materials, which exhibit
      enhanced cytotoxicity. The versatility of the click modulation protocol will
      allow a wide range of MOFs to be easily surface functionalized for a number of
      applications.

PMID- 28516171
TI  - Boundary Negotiating Artifacts in Personal Informatics: Patient-Provider
      Collaboration with Patient-Generated Data.
AB  - Patient-generated data is increasingly common in chronic disease care management.
      Smartphone applications and wearable sensors help patients more easily collect
      health information. However, current commercial tools often do not effectively
      support patients and providers in collaboration surrounding these data. This
      paper examines patient expectations and current collaboration practices around
      patient-generated data. We survey 211 patients, interview 18 patients, and re
      analyze a dataset of 21 provider interviews. We find that collaboration occurs in
      every stage of self-tracking and that patients and providers create boundary
      negotiating artifacts to support the collaboration. Building upon current
      practices with patient-generated data, we use these theories of patient and
      provider collaboration to analyze misunderstandings and privacy concerns as well
      as identify opportunities to better support these collaborations. We reflect on
      the social nature of patient-provider collaboration to suggest future development
      of the stage-based model of personal informatics and the theory of boundary
      negotiating artifacts.

PMID- 28516172
TI  - Supporting Patient-Provider Collaboration to Identify Individual Triggers using
      Food and Symptom Journals.
AB  - Patient-generated data can allow patients and providers to collaboratively
      develop accurate diagnoses and actionable treatment plans. Unfortunately,
      patients and providers often lack effective support to make use of such data. We
      examine patient-provider collaboration to interpret patient-generated data. We
      focus on irritable bowel syndrome (IBS), a chronic illness in which particular
      foods can exacerbate symptoms. IBS management often requires patient-provider
      collaboration using a patient's food and symptom journal to identify the
      patient's triggers. We contribute interactive visualizations to support
      exploration of such journals, as well as an examination of patient-provider
      collaboration in interpreting the journals. Drawing upon individual and
      collaborative interviews with patients and providers, we find that collaborative
      review helps improve data comprehension and build mutual trust. We also find a
      desire to use tools like our interactive visualizations within and beyond clinic
      appointments. We discuss these findings and present guidance for the design of
      future tools.

PMID- 28516173
TI  - Reconsidering the Device in the Drawer: Lapses as a Design Opportunity in
      Personal Informatics.
AB  - People stop using personal tracking tools over time, referred to as the lapsing
      stage of their tool use. We explore how designs can support people when they
      lapse in tracking, considering how to design data representations for a person
      who lapses in Fitbit use. Through a survey of 141 people who had lapsed in using
      Fitbit, we identified three use patterns and four perspectives on tracking.
      Participants then viewed seven visual representations of their Fitbit data and
      seven approaches to framing this data. Participant Fitbit use and perspective on
      tracking influenced their preference, which we surface in a series of contrasts.
      Specifically, our findings guide selecting appropriate aggregations from Fitbit
      use (e.g., aggregate more when someone has less data), choosing an appropriate
      framing technique from tracking perspective (e.g., ensure framing aligns with how
      the person feels about tracking), and creating appropriate social comparisons
      (e.g., portray the person positively compared to peers). We conclude by
      discussing how these contrasts suggest new designs and opportunities in other
      tracking domains.

PMID- 28516174
TI  - When Personal Tracking Becomes Social: Examining the Use of Instagram for Healthy
      Eating.
AB  - Many people appropriate social media and online communities in their pursuit of
      personal health goals, such as healthy eating or increased physical activity.
      However, people struggle with impression management, and with reaching the right
      audiences when they share health information on these platforms. Instagram, a
      popular photo-based social media platform, has attracted many people who post and
      share their food photos. We aim to inform the design of tools to support healthy
      behaviors by understanding how people appropriate Instagram to track and share
      food data, the benefits they obtain from doing so, and the challenges they
      encounter. We interviewed 16 women who consistently record and share what they
      eat on Instagram. Participants tracked to support themselves and others in their
      pursuit of healthy eating goals. They sought social support for their own
      tracking and healthy behaviors and strove to provide that support for others.
      People adapted their personal tracking practices to better receive and give this
      support. Applying these results to the design of health tracking tools has the
      potential to help people better access social support.

PMID- 28516177
TI  - Insight into the phase evolution of a NiMgAl catalyst from the reduction stage to
      the post-reaction stage during the dry reforming of methane.
AB  - Herein, phase evolution of a NiMgAl oxide catalyst at the reduction stage was
      qualitatively analysed and quantitatively determined by employing the continuous
      changes in its XRD intensity and TPR information. The stable crystallite size of
      both the active metal and spinel support was responsible for the long stability
      of the NiMgAl catalyst without carbon deposition during the DRM reaction.

PMID- 28516175
TI  - TummyTrials: A Feasibility Study of Using Self-Experimentation to Detect
      Individualized Food Triggers.
AB  - Diagnostic self-tracking, the recording of personal information to diagnose or
      manage a health condition, is a common practice, especially for people with
      chronic conditions. Unfortunately, many who attempt diagnostic self-tracking have
      trouble accomplishing their goals. People often lack knowledge and skills needed
      to design and conduct scientifically rigorous experiments, and current tools
      provide little support. To address these shortcomings and explore opportunities
      for diagnostic self-tracking, we designed, developed, and evaluated a mobile app
      that applies a self-experimentation framework to support patients suffering from
      irritable bowel syndrome (IBS) in identifying their personal food triggers.
      TummyTrials aids a person in designing, executing, and analyzing self-experiments
      to evaluate whether a specific food triggers their symptoms. We examined the
      feasibility of this approach in a field study with 15 IBS patients, finding that
      participants could use the tool to reliably undergo a self-experiment. However,
      we also discovered an underlying tension between scientific validity and the
      lived experience of self-experimentation. We discuss challenges of applying
      clinical research methods in everyday life, motivating a need for the design of
      self-experimentation systems to balance rigor with the uncertainties of everyday
      life.

PMID- 28516176
TI  - Examining Menstrual Tracking to Inform the Design of Personal Informatics Tools.
AB  - We consider why and how women track their menstrual cycles, examining their
      experiences to uncover design opportunities and extend the field's understanding
      of personal informatics tools. To understand menstrual cycle tracking practices,
      we collected and analyzed data from three sources: 2,000 reviews of popular
      menstrual tracking apps, a survey of 687 people, and follow-up interviews with 12
      survey respondents. We find that women track their menstrual cycle for varied
      reasons that include remembering and predicting their period as well as informing
      conversations with healthcare providers. Participants described six methods of
      tracking their menstrual cycles, including use of technology, awareness of their
      premenstrual physiological states, and simply remembering. Although women find
      apps and calendars helpful, these methods are ineffective when predictions of
      future menstrual cycles are inaccurate. Designs can create feelings of exclusion
      for gender and sexual minorities. Existing apps also generally fail to consider
      life stages that women experience, including young adulthood, pregnancy, and
      menopause. Our findings encourage expanding the field's conceptions of personal
      informatics.

PMID- 28516178
TI  - A multi-walled carbon nanotube-zinc oxide nanofiber based flexible chemiresistive
      biosensor for malaria biomarker detection.
AB  - We report the fabrication of a flexible, lightweight and disposable multi walled
      carbon nanotube (MWCNT)-zinc oxide (ZnO) nanofiber based chemiresistive biosensor
      for label free detection of the malaria biomarker, histidine rich protein II
      (HRP2). The sensing platform is formed by depositing nanofibers in between the
      source and drain electrodes patterned on a thin, flexible polyethylene
      terephthalate (PET) substrate. MWCNT-ZnO nanofibers are synthesized via the
      electrospinning technique followed by a calcination process. This approach
      creates functional groups on the nanofiber surface that are used for the one step
      immobilization of HRP2 antibodies without further surface modification. The
      device exhibits a good sensitivity of 8.29 kOmega g-1 mL and a wide detection
      range of 10 fg mL-1-10 ng mL-1, and it is specific towards the targeted HRP2
      biomarker. To the best of our knowledge, this is the first report on a flexible
      chemiresistive biosensor explored for the detection of the malaria biomarker and
      can be extended in the future to several other biomarker detection systems
      towards smart point-of-care (POC) diagnostics.

PMID- 28516179
TI  - alpha-Diazo oxime ethers for N-heterocycle synthesis.
AB  - This Feature Article introduces the preparation and synthetic utility of alpha
      diazo oxime ethers. alpha-Oximino carbenes are useful synthons for N
      heterocycles, and can be easily prepared from alpha-diazo oxime ethers as
      precursors. We begin with the preparation of alpha-diazo oxime ethers and their
      application in [3+2] cycloaddition. It turns out that the nature of metals bound
      to carbenes plays a crucial role in modulating the reactivity of alpha-oximino
      carbenes, in which copper carbenes smoothly react with enamines, whereas the less
      reactive enol ethers and nitriles require gold carbenes. In Section 3.2, a
      discussion on N-O and C-H bond activation is presented. Carbenes derived from
      diazo oxime ethers show unique reactivity towards N-O and C-H bond activation, in
      which the proximity of the two functionalities, carbene and oxime ether, dictates
      the preferred reaction pathways toward pyridines, pyrroles, and 2H-azirines. In
      Section 3.3, the development of tandem reactions based on alpha-diazo oxime
      ethers is discussed. The nature of carbenes in which whether free carbenes or
      metal complexes are involved dissects the pathway and forms different types of 2H
      azirines. The 2H-azirine formation turned out to be an excellent platform for the
      tandem synthesis of N-heterocycles including pyrroles and pyridines. In the last
      section, we describe the electrophilic activation of 2H-azirines with vinyl
      carbenes and oximino carbenes. The resulting azirinium species undergo rapid ring
      expansion rearrangements to form pyridines and pyrazines.

PMID- 28516180
TI  - Near infrared two photon imaging using a bright cationic Yb(iii) bioprobe
      spontaneously internalized into live cells.
AB  - An Yb(iii) complex based on a dimethyl cyclen macrocyclic ligand functionalized
      by charge transfer antennae was prepared. This cationic [YbL3]+ complex is stable
      and soluble in water and presents interesting photophysical nonlinear properties.
      It is spontaneously internalized and accumulates in live cells. High quality
      images have been obtained both in a classical NIR-to-vis configuration and in the
      more challenging NIR-to-NIR one.

PMID- 28516181
TI  - A pulse electrosynthesized nanoporous nickel oxyhydroxide-borate thin film in
      electro- and photoelectro-reforming of methanol for selective production of
      formate.
AB  - An nanoporous nickel oxyhydroxide-borate (NiBi) thin film, consisting of an
      aggregate of spherical particles self-assembled from NiBi nanopetals, has been
      synthesized using a simple and cost-effective pulse electrodeposition method
      without the addition of any surfactant, and demonstrated as an efficient,
      selective, and robust electrocatalyst in the electrochemical and
      photoelectrochemical reforming of methanol into formate.

PMID- 28516182
TI  - Intracellular accumulation and immunological responses of lipid modified magnetic
      iron nanoparticles in mouse antigen processing cells.
AB  - Understanding the effects of magnetic iron nanoparticles (MINPs) on the immune
      response is vitally important for biomedical applications such as cancer therapy,
      disease diagnosis and novel cancer imaging. In this study, lipid modified MINPs
      were designed and prepared by introducing the neutral lipid DSPE-PEG or the
      zwitterionic lipid DSPE-PCB into hydrophobic MINPs through hydrophobic
      interaction (L-MINPs and ZL-MINPs, respectively). The effect of L-MINPs and ZL
      MINPs on the intracellular accumulation and immune responses of three kinds of
      antigen processing cells was examined. The results indicated that the high
      cellular uptake efficiency of surface coated MINPs was strongly related to the
      nature of the coating lipid, with the zwitterionic lipid being more effective
      than PEGylated ones. Besides, the results from flow cytometry (FCM), confocal
      laser scanning microscopy (CLSM) and Prussian blue staining demonstrated a time-
      and concentration-dependent MINP internalization. The uptake of zwitterionic
      lipid modified MINPs (ZL-MINPs) induced very low cytotoxicity and a strong mixed
      Th1/Th2 type immune response. L-MINPs could induce a strong increase in pro
      inflammatory cytokines with a slight secretion of Th2 cytokines. Besides, no IL
      10 was observed in both groups, indicating that MINPs with lipid modification
      were absence of immunosuppression. In conclusion, this study addresses an
      important implication of the lipid type and Fe concentration on the immune
      stimulation of cells and supports the potential for further development of
      biomedical applications.

PMID- 28516187
TI  - [The aged scalp : A dermato-oncological focus point].
AB  - Non-melanoma skin cancer and its precursor lesions are common diagnoses in
      dermatological practice, due to rising incidence and prevalence. Diagnosis is
      often clinical with subsequent histological confirmation. First-choice treatment
      for invasive carcinomas is complete surgical excision. Other therapeutic options,
      such as radiation or systemic therapies, should only be considered when excision
      is impossible. Mostly located on parts of the scalp that are poorly visible and
      accessible, particularly for elderly patients, these lesions are a challenge for
      physicians and patients alike. Especially regarding precursor lesions, the
      therapeutic options are numerous and should be adapted to the individual patient.
      The main risk factor for development of non-melanoma skin cancer and its
      precursor lesions is chronic UV exposure. A possible occupational context should
      always be considered. Preventative methods based on patient education and
      adequate sun protection behavior are particularly important. The prognosis of non
      melanoma skin cancer improves significantly with early diagnosis, as well as with
      guideline-compatible treatment and follow-up.

PMID- 28516190
TI  - [Is there still a role for active surveillance in prostate cancer?]
AB  - Long-term data demonstrate a higher oncological risk associated with active
      surveillance (AS) than initially anticipated. In particular, patients with more
      than two tumor-involved biopsy cores and/or Gleason-7a foci must be regarded as
      having an increased risk of developing an incurable stage of disease after an
      initial attempt of AS. For patients with Gleason-7a foci, the 15-year risk of
      suffering from an incurable tumor stage is reported as high as 60%. Furthermore,
      life expectancy must be regarded as one of the major risk factors to finally
      develop symptomatic incurable disease. A discussion has therefore started as to
      whether a high life expectancy should be regarded as an exclusion criterion
      against AS. An estimated life expectancy exceeding 15 or 20 years has been
      proposed for patients suffering from Gleason 7a or 6 foci at initial biopsy,
      respectively. Furthermore, it must be expected that a number of molecular risk
      factors will gain importance in the near future for the decision-making process
      for or against AS.

PMID- 28516191
TI  - [Unexpected finding in a case of oculomotor nerve paresis].

PMID- 28516188
TI  - Management of bilateral Wilms tumours.
AB  - Wilms tumour is named after Max Wilms. It is an embryonal tumour derived from the
      metanephros. It is the commonest childhood renal tumour and the third commonest
      paediatric malignancy. Synchronous bilateral Wilms tumours (BWT) represent 4-7%
      of all Wilms tumours (WT) and present at a younger age than unilateral Wilms
      tumours. At least 10% of synchronous BWTs have unfavourable histology, and up to
      22% are associated with genitourinary abnormalities, aniridia, WAGR syndrome,
      Denys-Drash syndrome, hemihypertrophy, or one of the other overgrowth syndromes.
      The long-term disease-free survival rate for patients with unilateral WT is
      approaching 90%, and is around 70% for those with metastatic disease. For both
      synchronous and metachronous Wilms tumours the prognosis is less favourable with
      reported cure rates approaching 80% in the best centres and lower in resource
      poor settings. There is potential for a reduced quality of life due to renal
      insufficiency and the possible need for renal transplantation. The major clinical
      challenge in BWTs is preservation of functioning renal tissue using nephron
      sparing surgical techniques, while achieving cure with minimum therapy-related
      morbidity. Mortality is generally associated with progressive disease of
      anaplastic tumours. Chemotherapy followed by nephron-sparing surgery has been
      able, in most cases, to eradicate the tumour while preserving renal function.
      Radiotherapy has largely been avoided because of fears of long-term radiation
      injury to the residual functioning renal mass. Patient selection, appropriate pre
      and post-operative chemotherapy and skilled surgical techniques all contribute
      to excellent outcomes where these are achievable.

PMID- 28516189
TI  - Improving the rigour of VACTERL screening for neonates with anorectal
      malformations.
AB  - PURPOSE: Screening investigations for the vertebral, anorectal, cardiac, tracheo
      oesophageal, renal and limb (VACTERL) association form an important part of the
      management of neonates with anorectal malformations (ARMs). We developed a
      proforma to define investigations and indications for referral. The aim of the
      current study was to determine if the proforma could improve screening rigour.
      METHODS: Four centres performed a 3-year retrospective audit of neonates with
      ARM. Following introduction of a proforma, the same data were collected
      prospectively for consecutive neonates over a further 2 years. The appropriate
      investigation of each component of the VACTERL association and the corresponding
      referral required for each abnormal result were defined. The proportion of
      patients undergoing appropriate investigation and referral was compared against
      these standards. An audit standard of 90% was set for each criteria. RESULTS:
      Prior to implementation of the proforma, 86 patients were audited, with a further
      69 patients after. The audit standard was met in 7 criteria before introduction
      of the proforma in comparison to 10 criteria afterwards. CONCLUSION: The
      completeness of VACTERL screening and its documentation improved following
      introduction of the proforma. Performance remains imperfect. Review of specific
      criteria (such as definition of vertebral body screening) will help address this.

PMID- 28516192
TI  - The value of Gesell score in predicting the outcome of cochlear implantation in
      children.
AB  - The purpose is to determine the value of preoperative evaluation on developmental
      levels using Gesell score in predicting the postoperative outcome in pediatric
      cochlear implantation (CI) recipients. 78 children who underwent CI were included
      in our study. Age at the time of CI ranged from 6 to 67 months. The Gesell score
      including adaptability, fine motor, gross motor, language, and social skill was
      used for evaluating the patients' developmental levels before the CI, and a
      developmental quotient (DQ) was calculated by the following formula:
      (developmental age/actual age) * 100. The auditory perception and speech
      production abilities were evaluated using the categories of auditory performance
      (CAP) and speech intelligibility rating (SIR) before CI and at 1 year after CI.
      The associations between the preoperative Gesell score/DQ and the improvement of
      postoperative CAP/SIR outcomes were analyzed. Preoperative developmental
      evaluation of CI candidates suggested that the developmental delay was common in
      children with profound hearing loss. The mean of language DQ (46.72 +/- 17.59)
      was significantly decreased than the mean of others' ability DQ in the enrolled
      children. The older the pediatric CI candidates were, the lower the DQ were.
      Age/adaptability DQ and improvement of postoperative CAP/SIR 1 year after CI were
      related. Age was negative correlation with the CI outcome and adaptability DQ was
      positive correlation with the CI outcome. The mean of CAP 1 year after CI was
      4.16, and the mean of SIR 1 year after CI was 2.03. The first logistics
      regression equation was Y1 = exp (-18.123 + 0.199 * adaptability DQ - 0.163 *
      age), and Y1 was the possibility which CAP was lower than 5 1 year after CI. The
      sensitivity of first regression equation was 84.2% and specificity was 70.8%. The
      second logistics regression equation was Y2 = exp (-23.347 + 0.268 * adaptability
      DQ - 0.164 * age), and Y2 was the possibility which SIR was lower than 3 1 year
      after CI. The sensitivity of second regression equation was 85.7% and specificity
      was 72.7%. Preoperative Gesell score may be value in predicting the postoperative
      outcome in pediatric CI recipients. The older children are more serious
      developmental delay occur, so the CI operation should be finished as early as
      possible. Adaptability DQ combined with age has predictive effect on the
      postoperative outcome of cochlear implantation in children.

PMID- 28516194
TI  - [Current legal and jurisdictional questions from the perspective of the German
      Federal Association for Geriatrics : Practical report].
AB  - The article discusses the questions of the arbitration bodies according to S 111b
      SGB V (Volume V of the Social Insurance Code) in the individual federal states
      from the perspective of geriatric rehabilitation hospitals. The content of the
      agreement of reimbursement between a rehabilitation hospital and health insurance
      will be targeted as well as the question whether the entire content of the
      agreements of reimbursement can be negotiated at the arbitration body. In
      addition, the authors describe the consequences of the jurisprudence of the
      Federal Social Court on S 301 I. S. 1 no. 8 SGB V and the reaction of the
      lawgiver. Furthermore the authors describe the effects of the jurisprudence of
      the Federal Social Court regarding the minimum age associated with complex
      geriatric treatment (OPS 8-550).

PMID- 28516193
TI  - Co-mutated CALR and MPL driver genes in a patient with myeloproliferative
      neoplasm.

PMID- 28516195
TI  - [10-year anniversary of the Long-term Care Charter : Time to take stock].
AB  - Ten years ago, the Charter for People in Need of Long-term Care was published in
      Germany. The Charter contains a series of basic rights for people in need of long
      term care. At the initiative of the Federal Ministry for Family Affairs, Senior
      Citizens, Women and Youth (BMFSFJ), this was developed in a complex consensus
      process together with the Federal Ministry of Health (BMG) and representatives
      from all areas of care. Since then, the Charter has gained practical relevance in
      various areas of care and has entered into legislation. The article looks at the
      dissemination and impact of the Charter following a review of the social and
      legal environment. Further implementation requirements and the revision of the
      charter are discussed.

PMID- 28516197
TI  - Optimized immunohistochemistry using the D5F3 antibody provides a reliable test
      for identification of ALK-positive lung adenocarcinomas.
AB  - We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection
      of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases
      positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ
      hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive
      (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC
      positive/FISH-negative cases, one was unsuitable for FISH and three had
      abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were
      FISH-negative. The FISH positive/IHC-positive cases with moderately intense
      reactivity had the typical clinicopathologic features of ALK-positive patients
      (younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01;
      cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In
      conclusion, our findings indicate that optimized IHC using the D5F3 antibody
      provides a reliable and inexpensive test for identification of ALK-positive
      adenocarcinomas. Inclusion of this information in the pathology report at the
      time of the histological diagnosis might significantly shorten time to treatment.

PMID- 28516198
TI  - [Local consolidative therapy improves progression-free survival in patients with
      oligometastatic NSCLC : Results of a randomized phase II study].

PMID- 28516196
TI  - Coupling dynamics in speech gestures: amplitude and rate influences.
AB  - Speech is a complex oral motor function that involves multiple articulators that
      need to be coordinated in space and time at relatively high movement speeds. How
      this is accomplished remains an important and largely unresolved empirical
      question. From a coordination dynamics perspective, coordination involves the
      assembly of coordinative units that are characterized by inherently stable
      coupling patterns that act as attractor states for task-specific actions. In the
      motor control literature, one particular model formulated by Haken et al. (Biol
      Cybern 51(5):347-356, 1985) or HKB has received considerable attention in the way
      it can account for changes in the nature and stability of specific coordination
      patterns between limbs or between limbs and external stimuli. In this model (and
      related versions), movement amplitude is considered a critical factor in the
      formation of these patterns. Several studies have demonstrated its role for
      bimanual coordination and similar types of tasks, but for speech motor control
      such studies are lacking. The current study describes a systematic approach to
      evaluate the impact of movement amplitude and movement duration on coordination
      stability in the production of bilabial and tongue body gestures for specific
      vowel-consonant-vowel strings. The vowel combinations that were used induced a
      natural contrast in movement amplitude at three speaking rate conditions (slow,
      habitual, fast). Data were collected on ten young adults using electromagnetic
      articulography, recording movement data from lips and tongue with high temporal
      and spatial precision. The results showed that with small movement amplitudes
      there is a decrease in coordination stability, independent from movement
      duration. These findings were found to be robust across all individuals and are
      interpreted as further evidence that principles of coupling dynamics operate in
      the oral motor control system similar to other motor systems and can be explained
      in terms of coupling mechanisms between neural oscillators (organized in
      networks) and effector systems. The relevance of these findings for understanding
      motor control issues in people with speech disorders is discussed as well.

PMID- 28516199
TI  - Cloning and Stress-Induced Expression Analysis of Calmodulin in the Antarctic
      Alga Chlamydomonas sp. ICE-L.
AB  - Calmodulin (CaM) is a Ca2+-binding protein that plays a role in several Ca2+
      signaling pathways, which dynamically regulates the activities of hundreds of
      proteins. The ice alga Chlamydomonas sp. ICE-L, which has the ability to adapt to
      extreme polar conditions, is a crucial primary producer in Antarctic ecosystem.
      This study hypothesized that Cam helps the ICE-L to adapt to the fluctuating
      conditions in the polar environment. It first verified the overall length of Cam,
      through RT-PCR and RACE-PCR, based on partial Cam transcriptome library of ICE-L.
      Then, the nucleotide and predicted amino acid sequences were, respectively,
      analyzed by various bioinformatics approaches to gain more insights into the
      computed physicochemical properties of the CaM. Potential involvements of Cam in
      responding to certain stimuli (i.e., UVB radiation, high salinity, and
      temperature) were investigated by differential expression, measuring its
      transcription levels by means of quantitative RT-PCR. Results showed that CaM was
      indeed inducible and regulated by high UVB radiation, high salinity, and
      nonoptimal temperature conditions. Different conditions had different expression
      tendencies, which provided an important basis for investigating the adaptation
      mechanism of Cam in ICE-L.

PMID- 28516200
TI  - Respiratory viral infections are underdiagnosed in patients with suspected
      sepsis.
AB  - The study aim was to investigate the prevalence and clinical relevance of viral
      findings by multiplex PCR from the nasopharynx of clinically septic patients
      during a winter season. During 11 weeks of the influenza epidemic period in
      January-March 2012, consecutive adult patients suspected to be septic (n = 432)
      were analyzed with cultures from blood and nasopharynx plus multiplex PCR for
      respiratory viruses on the nasopharyngeal specimen. The results were compared
      with those from microbiology analyses ordered as part of standard care. During
      the winter season, viral respiratory pathogens, mainly influenza A virus, human
      metapneumovirus, coronavirus, and respiratory syncytial virus were clinically
      underdiagnosed in 70% of patients positive by the multiplex PCR assay. During the
      first four weeks of the influenza epidemic, few tests for influenza were ordered
      by clinicians, indicating low awareness that the epidemic had started.
      Nasopharyngeal findings of Streptococcus pneumoniae and Haemophilus influenzae by
      culture correlated to pneumonia diagnosis, and in those patients laboratory signs
      of viral co-infections were common but rarely suspected by clinicians. The role
      of respiratory viral infections in patients presenting with a clinical picture of
      sepsis is underestimated. Specific antiviral treatment might be beneficial in
      some cases and may reduce spread in a hospital setting. Diagnosing viral
      infections may promote reduction of unnecessary antibiotic use. It can also be a
      tool for decisions concerning patient logistics, in order to minimize exposure of
      susceptible patients and personnel.

PMID- 28516201
TI  - Budget impact and cost-effectiveness analyses of direct-acting antivirals for
      chronic hepatitis C virus infection in Hong Kong.
AB  - The purpose of this investigation was to evaluate the budget impact and cost
      effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C
      virus (HCV) infection in Hong Kong. A decision analytic model was developed to
      compare short-term costs and health outcomes of patients with chronic HCV
      genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based
      treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based
      treatments (sofosbuvir or ledipasvir/sofosbuvir or
      ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based
      treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171
      per course while improving the rate of sustained virologic response (SVR) from 59
      66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments
      ranged from $9724 to $29,189 per treatment success, which were all below the cost
      effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing
      DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection
      management over 5 years. A 50% change in DAA medication costs reflected a change
      in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are
      cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs
      to the public hospital formulary yields a considerable budget increase but is
      still economically favorable to the local government.

PMID- 28516203
TI  - [Erratum to: Surgical anatomy of the abdominal wall].

PMID- 28516202
TI  - [Plastic reconstruction of radiation injuries].
AB  - In addition to surgical and drug therapy, radiotherapy (or radiation therapy) is
      one of the three mainstays of modern oncological therapy regimes. It uses
      ionizing radiation to control tumors by damaging the DNA of cancerous tissue
      leading to cellular death. Although advances have been made in recent years
      resulting in a reduced dosage to the surrounding tissues, radiation injuries and
      tissue-related side effects cannot be completely avoided. Knowledge of the
      pathophysiology, treatment modalities and interdisciplinary treatment approaches
      are essential for effective therapy whilst limiting side effects. Surgery within
      the irradiated area is technically demanding due to tissue alterations and
      unpredictable wound healing. The plastic reconstructive surgeon either faces the
      challenge of delayed wound healing following neoadjuvant radiation or chronic
      radiation-linked changes following previous radiotherapy, which can also occur
      after a latency period of many years. Reconstructive interventions can be
      essential to repair deficits of a functional and/or aesthetic nature in order to
      maintain a high quality of life for oncology patients. This can also be of
      benefit to patients in a palliative oncological setting to improve daily
      functions and quality of life.

PMID- 28516205
TI  - Applications of white rot fungi in bioremediation with nanoparticles and
      biosynthesis of metallic nanoparticles.
AB  - White rot fungi (WRF) are important environmental microorganisms that have been
      widely applied in many fields. To our knowledge, the application performance of
      WRF in bioremediation can be greatly improved by the combination with
      nanotechnology. And the preparation of metallic nanoparticles using WRF is an
      emerging biosynthesis approach. Understanding the interrelation of WRF and
      nanoparticles is important to further expand their applications. Thus, this mini
      review summarizes the currently related reports mainly from the two different
      point of views. We highlight that nanoparticles as supports or synergistic agents
      can enhance the stability and bioremediation performance of WRF in wastewater
      treatment and the biosynthesis process and conditions of several important
      metallic nanoparticles by WRF. Furthermore, the potential toxicity of
      nanoparticles on WRF and challenges encountered are also discussed. Herein, we
      deem that this mini-review will strengthen the basic knowledge and provide
      valuable insight for the applications of WRF and nanoparticles.

PMID- 28516204
TI  - A Novel, Dynamic Statistical Model for Predicting Patient Satisfaction with
      Fundoplication Based on Pre-Operative Symptom Patterns.
AB  - BACKGROUND: Fundoplication provides excellent control of gastro-oesophageal
      reflux disease (GORD), but there remain a number of unsatisfied patients who have
      proven difficult to identify pre-operatively. We hypothesised that pre-operative
      symptom patterns can predict of the risk of post-operative dissatisfaction.
      METHODS: Pre-operative symptoms and post-operative satisfaction were measured
      using standardised questionnaires along with routine investigations. These data
      were used to calculate our novel pre-operative risk of dissatisfaction (PROD)
      score. Potential pre-operative prognostic markers were tested against the post
      operative satisfaction data, including the objective investigations and the PROD
      score. The prognostic utility of the PROD score and the Society of American
      Gastrointestinal and Endoscopic Surgeons (SAGES) guideline was tested using
      receiver operating characteristic analysis to determine the area under the curve
      (AUC). RESULTS: An association was found between our PROD score and each of the
      satisfaction measures (n = 225, p < 0.001) which is likely to be of prognostic
      utility (AUC = 0.67-0.79). No such association was found between the routine
      investigations and post-operative satisfaction. The PROD score was found to be of
      greater prognostic utility than the SAGES guideline (n = 166, p < 0.001).
      CONCLUSIONS: The PROD score is a novel, easy-to-use test that can predict
      individual patient satisfaction with fundoplication.

PMID- 28516206
TI  - Identification, expression and characterization of an R-omega-transaminase from
      Capronia semiimmersa.
AB  - Chiral amines are essential precursors in the production of biologically active
      compounds, including several important drugs. Among the biocatalytic strategies
      that have been developed for their synthesis, the use of omega-transaminases
      (omega-TA) appears as an attractive alternative allowing the stereoselective
      amination of prochiral ketones. However, the problems associated with narrow
      substrate specificity, unfavourable reaction equilibrium and expensive amine
      donors still hamper its industrial application. The search for novel enzymes from
      nature can contribute to expand the catalytic repertoire of omega-TA and help to
      circumvent some of these problems. A genome mining approach, based on the work
      described by Hohne et al., was applied for selection of potential R-omega-TA.
      Additional criteria were used to select an enzyme that differs from previously
      described ones. A candidate R-omega-TA from Capronia semiimmersa was selected,
      cloned and expressed in Escherichia coli. Interestingly, alignment of this enzyme
      with previously reported TA sequences revealed the presence of two additional
      amino acid residues in a loop close to the active site. The impact of this change
      was analysed with a structural model based on crystallized R-omega-TAs. Analysis
      of the substrate specificity of R-omega-TA from C. semiimmersa indicates that it
      accepts a diversity of ketones as substrates yielding the corresponding amine
      with good yields and excellent enantioselectivity. The expressed enzyme accepts
      isopropylamine as amine donor what makes it suitable for industrial processes.

PMID- 28516207
TI  - Enhancing H2O2 resistance of an esterase from Pyrobaculum calidifontis by
      structure-guided engineering of the substrate binding site.
AB  - Green technologies are attracting increasing attention in industrial chemistry
      where enzymatic reactions can replace dangerous and environmentally unfriendly
      chemical processes. In situ enzymatic synthesis of peroxycarboxylic acid is an
      attractive alternative for several industrial applications although concentrated
      H2O2 can denature the biocatalyst, limiting its usefulness. Herein, we report the
      structure-guided engineering of the Pyrobaculum calidifontis esterase (PestE)
      substrate binding site to increase its stability and perhydrolysis activity. The
      L89R/L40A PestE mutant showed better tolerance toward concentrated H2O2 compared
      with wild-type PestE, and retained over 72% of its initial activity after 24-h
      incubation with 2 M H2O2. Surprisingly, the half-life (t 1/2, 80  degrees C) of
      PestE increased from 28 to 54 h. The k cat/K m values of the mutant increased 21-
      and 3.4-fold toward pentanoic acid and H2O2, respectively. This work shows how
      protein engineering can be used to enhance the H2O2 resistance and catalytic
      efficiency of an enzyme.

PMID- 28516208
TI  - Safety and efficiency of active immunization with detoxified antigen against
      scorpion venom: side effect evaluation.
AB  - OBJECTIVE: The efficiency and safety of vaccine are the most important
      properties, however, as any medication, it can induce side effects. This
      prophylactic therapy could be used to prevent the lethal and pathophysiological
      effects induced after scorpion envenomation. METHODS: In this study, detoxified
      venom associated to alum adjuvant (V*alum) is used as a vaccine against scorpion
      venom for immunization of mice. We evaluate the safety and the inflammatory
      response of this vaccine. We also investigated the protective effect of this
      formulation against the toxicity of native Androctonus australis hector venom.
      RESULTS: Results showed no adverse events occurred after immunization of animals.
      This active immunization of animals did not cause change in vascular
      permeability, no edema formation in the studied organs. Furthermore, there are no
      IgE production in sera, nor change in the morphology of the mast cells in skin
      tissues. However, low inflammatory response triggered by activating the
      recruitment of eosinophils associated to IL-4 and IL-5 release was observed. All
      immunized animals are protected from the toxic effects of native venom until 6
      LD50 and to 7 LD50 after the second challenge. CONCLUSION: This safe vaccine
      preparation seems to induce a long-term protection without any risk of
      deleterious inflammatory response.

PMID- 28516209
TI  - Foreign Language Effect and Psychological Distance.
AB  - Does using a foreign language result in forming different moral decisions than
      using our mother tongue? Two studies were conducted to investigate whether there
      is a relationship between foreign language effects (differences between native
      vs. foreign language conditions) and psychological distance. Study 1 tested four
      moral dilemmas adapted from Greene et al. (Cognition 107: 1144-1155, 2008). Non
      fluent Korean-English bilingual participants (N = 161) indicated decisions
      regarding four moral dilemmas in either Korean or English languages. The study
      found that for personal moral conflict situations, in which emotion and automatic
      intuition were more important than deliberation, there were significant
      differences in ratios of utilitarian decisions between the native language (L1)
      and the foreign language (L2) conditions. The participants tended to make more
      utilitarian decisions in L2 than in L1, which implies reduced emotionality in L2.
      Study 2 examined whether the psychological distance increased using the foreign
      language (English) utilizing an automatic self-test. Nonproficient Korean-English
      bilinguals (N = 26) formed associations between three kinds of geometric shapes
      (ellipses, rectangles and triangles) and three kinds of labels ('me', 'friends'
      and 'others'). The results of the study found the self-bias effect decreased when
      labels were presented in the foreign language (in English). This implies that the
      foreign language effect resulted from the reduced emotional response, and
      deliberation in decision making which may result from increased psychological
      distance.

PMID- 28516210
TI  - Antibiotic resistance genes in surface water of eutrophic urban lakes are related
      to heavy metals, antibiotics, lake morphology and anthropic impact.
AB  - Urban lakes are impacted by heavy human activities and represent potential
      reservoirs for antibiotic resistance genes. In this study, six urban lakes in
      Wuhan, central China were selected to analyze the distribution of sulfonamide
      resistance (sul) genes, tetracycline resistance (tet) genes and quinolone
      resistance (qnr) genes and their relationship with heavy metals, antibiotics,
      lake morphology and anthropic impact. sul1 and sul2 were detected in all six
      lakes and dominated the types of antibiotic resistance genes, which accounted for
      86.28-97.79% of the total antibiotic resistance gene abundance. For eight tested
      tet genes, antibiotic efflux pumps (tetA, tetB, tetC, and tetG) genes were all
      observed in six lakes and had higher relative abundance than ribosomal protection
      protein genes (tetM and tetQ). For 4 plasmid mediated quinolone resistance genes,
      only qnrD is found in all six lakes. The class I integron (intI1) is also found
      to be a very important media for antibiotic resistance gene propagation in urban
      lakes. The results of redundancy analysis and variation partitioning analysis
      showed that antibiotic and co-selection with heavy metals were the major factors
      driving the propagation of antibiotic resistance genes in six urban lakes. The
      heavily eutrophic Nanhu Lake and Shahu Lake which located in a high density
      building area with heavy human activities had the higher relative abundance of
      total antibiotic resistance genes. Our study could provide a useful reference for
      antibiotic resistance gene abundance in urban lakes with high anthropic impact.

PMID- 28516211
TI  - Early endothelialization associated with a biolimus A9 bioresorbable polymer
      stent in a porcine coronary model.
AB  - Although Nobori(r), with a bioresorbable polymer and biolimus A9 abluminal
      coating, has unique characteristics, few data exist regarding endothelialization
      early after implantation. Fifteen Nobori(r) and 14 control bare-metal stents (S
      stentTM) were implanted in 12 pigs. Histopathology of stented segments,
      inflammation, and intimal fibrin content was evaluated on the 2nd and 14th day
      after implantation. On the 2nd day, endothelial cells were morphologically and
      immunohistologically confirmed on the surface of both stents, although some
      inflammatory cells might be involved. Stent surface endothelialization evaluated
      with a scanning electron microscope showed partial cellular coverage in both
      stents. On the 14th day, neointimal thickness and percentage of the neointimal
      area were significantly lower in Nobori(r) than in S-stentTM (51.4 +/- 4.5 vs.
      76.4 +/- 23.6 um, p < 0.05 and 10.8 +/- 2.6 vs. 14.1 +/- 4.2%, p < 0.01). No
      significant differences were found in these parameters on the 2nd day (17.3 +/-
      14.9 vs. 26.7 +/- 13.6 um and 3.7 +/- 3.0 vs. 6.7 +/- 3.7%), in inflammatory and
      intimal fibrin content scores. These results demonstrate that endothelialization
      could occur early after Nobori(r) implantation with similar inflammatory reaction
      to bare-metal stents, probably contributing to low frequency of in-stent
      thrombosis and restenosis.

PMID- 28516213
TI  - Expression of Concern: Aspirin attenuates insulin resistance in muscle of diet
      induced obese rats by inhibiting inducible nitric oxide synthase production and S
      nitrosylation of IRbeta/IRS-1 and Akt.

PMID- 28516212
TI  - Anatomical visualization of neural course and distribution of anterior ascending
      aortic plexus.
AB  - The aim of this study was to document the detailed anatomy of neural course and
      distribution on the anterior ascending aorta, to identify the high and low
      density areas of the anterior ascending aortic plexus for further understandings
      in cardiovascular surgery. The embalmed hearts of 42 elderly individuals were
      submacroscopically and microscopically examined, after excluding any that were
      macroscopically abnormal. With its origins in the anterior ascending aortic
      plexus, the right coronary plexus substantially innervated the right coronary
      artery, the right atrium and ventricle, and the sinus node. The intensive neural
      area extending from 10 mm lateral to the interatrial groove below the pericardial
      reflection as far as the right coronary artery opening contained almost all the
      right coronary plexus in 61.3% of patients, and more than 40.9% of the total
      nerve volume of the anterior ascending aortic plexus. Our findings suggest that
      the most superior and lateral area on the ascending aorta show the lowest neural
      density of right coronary component in the anterior ascending aortic plexus and
      the high density areas are invisible in right lateral field of view as seen in
      the right trans-axillary MICS approach.

PMID- 28516214
TI  - Interactions of cisplatin and the copper transporter CTR1 in human colon cancer
      cells.
AB  - There is much interest in understanding the mechanisms by which platinum-based
      anticancer agents enter cells, and the copper transporter CTR1 has been the focus
      of many recent studies. While there is a clinical correlation between CTR1 levels
      and platinum efficacy, cellular studies have provided conflicting evidence
      relating to the relationship between cisplatin and CTR1. We report here our
      studies of the relationship between cisplatin and copper homeostasis in human
      colon cancer cells. While the accumulation of copper and platinum do not appear
      to compete with each other, we did observe that cisplatin perturbs CTR1
      distribution within 10 min, a far shorter incubation time than commonly employed
      in cellular studies of cisplatin. Furthermore, on these short time-scales,
      cisplatin caused an increase in the cytoplasmic labile copper pool. While the
      predominant focus of studies to date has been on CTR1, these studies highlight
      the importance of investigating the interaction of cisplatin with other copper
      proteins.

PMID- 28516216
TI  - The role of intrauterine magnetic resonance in the management of myelomenigocele.
AB  - OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) in the
      management of myelomenigocele. BACKGROUND: Spinal dysraphism or neural tube
      defects (NTD) encompass a heterogeneous group of congenital spinal anomalies that
      result from the defective closure of the neural tube early in gestation.
      Myelomeningocele is the most common type of NTD that is compatible with life,
      with high survival rates but lifelong physical impairments. CONCLUSION: MRI is an
      important adjunct to ultrasound in assessing NTD, as it pertains to pre-surgical
      planning and perinatal management. However, it should not be considered a
      replacement for ultrasonography, which continues to be the gold standard for
      fetal anatomic evaluation.

PMID- 28516215
TI  - Are clinical findings of systemic titanium dispersion following implantation
      explained by available in vitro evidence? An evidence-based analysis.
AB  - Although the presence of titanium wear particles released into tissues is known
      to induce local inflammation following the therapeutic implantation of titanium
      devices into humans, the role that titanium ions play in adverse tissue responses
      has received little attention. Support that ongoing titanium ion release occurs
      is evidenced by the presence of ionic titanium bound to transferrin in blood, and
      ongoing excretion in the urine of patients with titanium devices. However, as
      reports documenting the presence of titanium within tissues do not distinguish
      between particulate and ionic forms due to technical challenges, the degree to
      which ionic titanium is released into tissues is unknown. To determine the
      potential for titanium ion release into tissues, this study evaluates available
      in vitro evidence relating to the release of ionic titanium under physiological
      conditions. This is a systematic literature review of studies reporting titanium
      ion release into solutions from titanium devices under conditions replicating the
      interstitial pH and constituents. Inclusion and exclusion criteria were defined.
      Of 452 articles identified, titanium ions were reported in nine media relevant to
      human biology in seventeen studies. Only one study, using human serum replicated
      both physiological pH and the concentration of constituents while reporting the
      presence of titanium ions. While there is insufficient information to explain the
      factors that contribute to the presence of titanium ions in serum of humans
      implanted with titanium devices, currently available information suggests that
      areas of future inquiry include the role of transferrin and organic acids.

PMID- 28516217
TI  - Prenatal surgery for myelomeningocele: review of the literature and future
      directions.
AB  - Open spina bifida or myelomeningocele (MMC) is one of the most common serious
      congenital malformations. Historically, this condition has been treated with
      closure of the MMC defect shortly after birth. The goal of postnatal closure is
      to cover the exposed spinal cord and prevent infection. However, postnatal
      surgery does not reverse or prevent the neurologic injury seen in MMC, reverse
      hindbrain herniation, or prevent hydrocephalus. The neurologic defects result
      from primary incomplete neurulation and secondary chronic prenatal damage to the
      exposed neural elements through mechanical and chemical trauma. In a hope to
      reduce the numerous surgical procedures, medical complications, and lifelong
      disabilities associated with MMC, the proposal of prenatal closure was put forth
      more than two decades ago. After promising results in animal models and some
      clinical series, a randomized controlled trial, the Management of
      Myelomeningocele Study (MOMS), was conducted. The MOMS trial demonstrated that
      closure during the prenatal period could be performed relatively safely and can
      result in significant benefit to the child. Specifically, prenatal closure
      results in improved motor function, reduced hindbrain herniation, and reduced
      need for a cerebral spinal fluid diversion. Long-term outcomes of the patients in
      the MOMS trial continues in the MOMS 2 study as these children grow.
      Additionally, investigations are underway on modifications to the open fetal MMC
      closure techniques.

PMID- 28516218
TI  - A high-fat diet can affect bone healing in growing rats.
AB  - A high-fat diet (HFD) can have a negative effect on bone quality in young and old
      people. Although bone healing in children is normally efficient, there is no
      evidence that children who have a diet rich in fat have compromised bone fracture
      regeneration compared with children with recommended dietary fat levels. The
      purpose of the present study was to evaluate the effects of an HFD on bone
      healing in growing female rats. Twenty-six postweaning female Wistar rats were
      divided into two groups (13 animals per group): a standard diet (SD) group and an
      HFD (with 60% of energy from fat) group. The rats received the assigned diets for
      5 weeks, and in the third week they were submitted to an osteotomy procedure of
      the left tibia. Body mass and feed intake were recorded during the experiment.
      One day before euthanasia, an insulin tolerance test was performed. After
      euthanasia, the tibiae were removed and analyzed by densitometry, mechanical
      testing, histomorphometry, stereology and immunohistochemistry. An HFD caused an
      adaptive response to maintain energetic balance by decreasing feed intake and
      causing insulin insensitivity. There was no change in bone mineral density,
      collagen amount and immunostaining for bone formation, but maximal load and
      stiffness were decreased in the HFD group. In addition, bone volume had a
      tendency to be higher in the SD group than in the HFD group. Compared with rats
      receiving an SD, growing rats receiving an HFD for 5 weeks had similar bone
      mineral density but altered mechanical properties at the osteotomy defect site.

PMID- 28516219
TI  - Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung
      cancer in TRPV1-deficient mice.
AB  - Bone pain is one of the most common and life-limiting complications of cancer
      metastasis to bone. Although the mechanism of bone pain still remains poorly
      understood, bone pain is evoked as a consequence of sensitization and excitation
      of sensory nerves (SNs) innervating bone by noxious stimuli produced in the
      microenvironment of bone metastases. We showed that bone is innervated by
      calcitonin gene-related protein (CGRP)+ SNs extending from dorsal root ganglia
      (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung
      cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia
      and flinching with increased CGRP+ SNs in bone and augmented SN excitation in DRG
      as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons.
      Immunohistochemical examination of LLC-injected bone revealed that the tumor
      microenvironment is acidic. Bafilomycin A1, a selective inhibitor of H+ secretion
      from vacuolar proton pump, significantly alleviated bone pain, indicating that
      the acidic microenvironment contributes to bone pain. We then determined whether
      the transient receptor potential vanilloid 1 (TRPV1), a major acid-sensing
      nociceptor predominantly expressed on SNs, plays a role in bone pain by
      intratibially injecting LLC cells in TRPV1-deficient mice. Bone pain and SN
      excitation in the DRG and spinal dorsal horn were significantly decreased in
      TRPV1 -/- mice compared with wild-type mice. Our results suggest that TRPV1
      activation on SNs innervating bone by the acidic cancer microenvironment in bone
      contributes to SN activation and bone pain. Targeting acid-activated TRPV1 is a
      potential therapeutic approach to cancer-induced bone pain.

PMID- 28516221
TI  - Small bowel obstruction due to ingestion of rubber balls.
AB  - We report a case of a 10-month-old girl who presented with a 10-day history of
      emesis that became bilious on the last day. The initial evaluation suggested
      small bowel obstruction. An upper gastrointestinal study confirmed the normal
      location of the duodenojejunal junction with normal rotation and no evidence of
      midgut volvulus. Ultrasound (US) evaluation demonstrated two intraluminal lesions
      that do not follow the typical features of solid or cystic lesions. Two rubber
      balls were found at surgery to be responsible for the small bowel obstruction.
      Foreign body ingestion is common in children, but this case demonstrates a
      unusual foreign object to be ingested as well as the US appearance of this
      particular foreign body.

PMID- 28516220
TI  - Prevalence and factors associated with supportive care needs among newly
      diagnosed Mexican breast cancer patients.
AB  - PURPOSE: Mexican breast cancer patients are generally diagnosed in advanced
      stages of the disease and often experience delays in cancer treatment delivery.
      Currently, little is known about these patients' psychological care needs. This
      study assessed levels and correlates of supportive care needs of Mexican breast
      cancer patients around the time of cancer diagnosis. METHODS: One hundred seventy
      three newly diagnosed Mexican breast cancer patients participated in the study.
      Supportive care needs, anxiety, depression, and patients' sociodemographic and
      clinical characteristics were assessed. Multiple regression analyses were used to
      examine factors associated with care needs. RESULTS: Up to 44% of patients showed
      unmet care needs. Health system/information needs were the most prevalent (68%),
      while physical/daily living needs the least (19%). Level of depressive symptoms
      was most consistently related to care needs. Patients with higher levels of
      depressive symptoms had higher psychological (beta = 0.38), physical/daily living
      (beta = 0.43), patient care/support (beta = 0.17), and additional unmet care
      needs (beta = 0.30), than patients with lower levels of depressive symptoms.
      CONCLUSIONS: This study suggests that mainly health system/information needs
      arise at the time of cancer diagnosis among Mexican breast cancer patients.
      Patients suffering high levels of depressive symptoms reported the highest levels
      of unmet needs. Future studies should be conducted to elucidate the care needs
      throughout the disease trajectory, as such information can inform health care
      professionals and policy makers and lead to improvements in the organization and
      provision of health care services for Mexican breast cancer patients.

PMID- 28516222
TI  - Population data of 17 Y-STRs (Yfiler) from Punjabis and Kashmiris of Pakistan.
AB  - Pakistan harbors 16 major ethnic groups including Punjabis (56% of total
      population) and Kashmiri (6% of total population). Here, we report data of 17 Y
      chromosomal short tandem repeats (Y-STRs) genotyped with the AmpFlSTR Y-filerTM
      PCR Amplification kit in 94 Punjabis and 101 Kashmiris. The estimated haplotype
      diversity was higher in Punjabis (0.996) than that in Kashmiris (0.983).
      Furthermore, we performed population genetic analyses by including data from six
      other Pakistani groups. The presented haplotype data were recently included in
      the Y-Chromosome Haplotype Reference Database (YHRD) for future forensic and
      other usage.

PMID- 28516225
TI  - A case of bilateral keratitis caused by Providencia alcalifaciens: a rarely
      encountered ocular pathogen.
AB  - PURPOSE: To report a case of keratitis caused by Providencia alcalifaciens.
      METHODS: A 70-year-old man presented with pain, redness, and decreased vision in
      both of his eyes. On initial presentation, the visual acuity in both of his eyes
      was hand motion, and slit lamp examination showed diffuse infiltrates and total
      epithelial defects of the cornea, conjunctival hyperemia, and severe anterior
      chamber reactions with 2-mm-height hypopyon. The results of laboratory studies
      revealed elevated liver function tests, which indicated the presence of alcoholic
      liver disease. RESULTS: The culture result was positive for P. alcalifaciens and
      showed sensitivity to ceftazidime and amikacin but resistant to cefazolin,
      gentamicin, fluoroquinolone, and ampicillin. He was treated with topical
      application and intravenous injection of ceftazidime. His keratitis resolved
      gradually over 3 months as the treatment dose was tapered and the treatment was
      eventually discontinued. His final visual acuity was 20/200 in the right eye and
      20/60 in the left eye because of the remaining central corneal opacity.
      CONCLUSIONS: We report a first case of keratitis due to P. alcalifaciens in a
      chronic heavy alcohol drinker. Ophthalmologists should consider this bacterium as
      a potential pathogen of corneal ulceration, when clinically suspect gram-negative
      bacterial keratitis especially in immunocompromised state.

PMID- 28516223
TI  - Two stage revision hip arthroplasty in periprosthetic joint infection. Comparison
      study: with or without the use of a spacer.
AB  - PURPOSE: The aim of this study was to compare two methods of two-stage surgery
      for PJI (periprosthetic joint infection) after THA (total hip arthroplasty): one
      with and one without the use of an antibiotic-loaded cement spacer. METHODS: This
      retrospective study was performed on 99 consecutive patients (99 hips) with a
      minimum follow-up of 24 months. Patients were divided into two groups: (1) in
      whom the operation was performed using a spacer, and (2) for whom a spacer was
      not used. RESULTS: For the whole cohort, the results improved between pre
      operative and final follow-up. Recurrence of infection was found in nine out of
      98 patients (9.2%) and was not significantly different between the two groups.
      Patients treated with a spacer had better functional improvement in the interim
      period, but the VAS score was better in the non-spacer group. The improvement in
      final function was better in the spacer group with regard to HHS, but not
      according to WOMAC score or VAS at final follow-up. CONCLUSION: The resection
      arthroplasty should be awarded particular consideration in cases of poor soft
      tissue quality, bone stock deficiency, when complications related to spacer use
      are expected or chances of new hip endoprosthesis implantation are low.

PMID- 28516226
TI  - Benefit of adding digital breast tomosynthesis to digital mammography for breast
      cancer screening focused on cancer characteristics: a meta-analysis.
AB  - PURPOSE: We evaluated the benefit of adding digital breast tomosynthesis (DBT) to
      full-field digital mammography (FFDM) compared to FFDM alone for breast cancer
      detection, focusing on cancer characteristics. METHODS: We searched electronic
      databases and relevant references for published studies comparing DBT plus FFDM
      to FFDM alone for breast cancer screening. Pooled risk ratios (RRs) for various
      pathologic findings were determined using random effects models. RESULTS: Eleven
      eligible studies were included. Pooled RRs showed a greater cancer detection for
      DBT plus FFDM than for FFDM alone for invasive cancer (1.327; 95% CI, 1.168
      1.508), stage T1 (1.388; 95% CI, 1.137-1.695), nodal-negative (1.451; 95% CI,
      1.209-1.742), all histologic grades (grade I, 1.812; grade II/III, 1.403), and
      histologic types of invasive cancer (ductal, 1.437; lobular, 1.901). However,
      adding DBT did not increase for detection of carcinoma in situ (1.198; 95% CI,
      0.942-1.524), stage >=T2 (1.391; 95% CI, 0.895-2.163), or nodal-positive cancer
      (1.336; 95% CI, 0.921-1.938). Heterogeneity among studies was not significant in
      any subset analysis. CONCLUSIONS: Adding DBT to FFDM enabled detection of early
      invasive breast cancer that might have been missed with FFDM alone. Knowing which
      cancer characteristic DBT detects may allow it to play a complementary role in
      predicting long-term patient outcomes and facilitate treatment planning.

PMID- 28516227
TI  - Impairment in Mismatch Negativity but not Repetition Suppression in
      Schizophrenia.
AB  - Schizophrenia is characterized by impaired auditory-evoked potentials (AEPs),
      mismatch negativity (MMN), and sensory gating of AEPs to repeated stimuli
      (repetition suppression, RS). In the predictive modeling framework, MMN and RS
      reflect encoding of prediction error and model sharpening, respectively. We
      compared P50, N100, P200 RS, and pitch and duration MMN in 26 participants
      diagnosed with schizophrenia (SZ) and 26 matched healthy controls (HC), and
      assessed relationships between MMN, RS, and SZ diagnosis. RS was measured by
      comparing responses to individual tones presented as 5-tone groups (1 kHz, 75 dB,
      50 ms, 5 ms rise/fall times, 330 ms SOA), separated by a 750 ms inter-trial
      interval. For MMN, the same tones were presented, with occasional pitch (1.2 kHz,
      10%) or duration deviants (100 ms, 10%) interspersed. Pitch and duration MMN were
      reduced in SZ (p < 0.01). There were no group differences in P50 RS, N100 RS, or
      P200 RS (p's > 0.1). Importantly, although pitch and duration MMN both correlated
      with RS of AEPs within the MMN time range (p's < 0.01), SZ diagnosis predicted
      MMN over and above RS (p < 0.05) and shared little variance with RS in prediction
      of MMN amplitude (tolerance > 0.93). We suggest that reduced MMN in SZ is related
      to deficits in encoding prediction error but not repetition suppression.

PMID- 28516228
TI  - Great sandeel (Hyperoplus lanceolatus) as a putative transmitter of parasite
      Contracaecum osculatum (Nematoda: Anisakidae).
AB  - In the Baltic Sea, the great sandeel (Hyperoplus lanceolatus), a common fish
      species that inhabits sandy substrates, is an important element in the diet of
      marine mammals, sea birds, and piscivorous fish. It can also act as a transmitter
      of parasites to its predators, but parasitological studies on this species are
      limited. We sampled great sandeels in April 2016 in two areas of the southern
      Baltic Sea (SB-south of Bornholm and GG-the Gulf of Gdansk) and found parasitic
      anisakid nematodes in both locations. The only one species of nematode parasites
      has been detected: liver worm (Contracaecum osculatum) with average prevalence of
      infection 8.96%. This is the first study to report on infection of H. lanceolatus
      with anisakid nematodes in the southern Baltic Sea and our results suggest that
      the great sandeel may play a role in the transmission of liver worm in the food
      web of this marine environment.

PMID- 28516229
TI  - Letter to the Editor concerning "The effect of total hip arthroplasty on sagittal
      spinal-pelvic-leg alignment and low back pain in patients with severe hip
      osteoarthritis" by W. Weng et al. Eur Spine J (2016);25(11):3608-3614.

PMID- 28516224
TI  - Psychiatric behaviors associated with cytoskeletal defects in radial neuronal
      migration.
AB  - Normal development of the cerebral cortex is an important process for higher
      brain functions, such as language, and cognitive and social functions.
      Psychiatric disorders, such as schizophrenia and autism, are thought to develop
      owing to various dysfunctions occurring during the development of the cerebral
      cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex
      process, which is achieved by strict control of cytoskeletal dynamics, and
      impairments in this process are suggested to cause various psychiatric disorders.
      Our recent findings indicate that radial neuronal migration as well as
      psychiatric behaviors is rescued by controlling microtubule stability during the
      embryonic stage. In this review, we outline the relationship between psychiatric
      disorders, such as schizophrenia and autism, and radial neuronal migration in the
      cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment
      strategies for psychiatric disorders will be discussed.

PMID- 28516230
TI  - Diverse roles of Dpb2, the non-catalytic subunit of DNA polymerase epsilon.
AB  - Timely progression of living cells through the cell cycle is precisely regulated.
      This involves a series of phosphorylation events which are regulated by various
      cyclins, activated in coordination with the cell cycle progression.
      Phosphorylated proteins govern cell growth, division as well as duplication of
      the genetic material and transcriptional activation of genes involved in these
      processes. A subset of these tightly regulated genes, which depend on the MBF
      transcription factor and are mainly involved in DNA replication and cell
      division, is transiently activated at the transition from G1 to S phase. A
      Saccharomyces cerevisiae mutant in the Dpb2 non-catalytic subunit of DNA
      polymerase epsilon (Polepsilon) demonstrates abnormalities in transcription of
      MBF-dependent genes even in normal growth conditions. It is, therefore, tempting
      to speculate that Dpb2 which, as described previously, participates in the early
      stages of DNA replication initiation, has an impact on the regulation of
      replication-related genes expression with possible implications for genomic
      stability.

PMID- 28516231
TI  - Molecular evolution of type II MAGE genes from ancestral MAGED2 gene and their
      phylogenetic resolution of basal mammalian clades.
AB  - Type II melanoma-associated antigens (MAGE) are a subgroup of about a dozen
      proteins found in various locations in the genome and expressed in normal
      tissues, thus are not related to cancer as the type I MAGE genes. This gene
      family exists as a single copy in non-mammals and monotremata, but found as two
      copies in metatherians and occur as a diverse group in all eutherians. Our
      studies suggest MAGED2 as the ancestor of this subfamily and the most likely
      evolutionary history of eutherian type II MAGE genes is hereby proposed based on
      synteny conservation, phylogenetic relations, genome location, homology
      conservation, and the protein and gene structures. Type II genes can be divided
      into two: those with 13 exons (MAGED1, MAGED2, TRO, and MAGED4) and those with
      only one exon (MAGEE1, MAGEE2, MAGEF1, NSMCE3, MAGEH1, MAGEL2, and NDN) with
      different evolutionary patterns. Our results suggest a need to change the gene
      nomenclature to MAGE1 (the ancestral gene), currently designated as LOC103095671
      and LOC100935086, in opossum and Tasmanian devil, respectively, and MAGE2 (the
      duplicated one), currently designated as LOC100617402 and NDNL2, respectively, to
      avoid confusion. We reconstructed the phylogenetic relationships among 23
      mammalian species using the combined sequences of MAGED1, MAGED2, MAGEL2, and
      NDN, because of their high divergence, and found high levels of support, being
      able to resolve the phylogenetic relationships among Euarchontoglires,
      Laurasiatheria, Afrotheria, and Xenarthra, as an example that small, but
      phylogenetically informative sequences, can be very useful for resolving basal
      mammalian clades.

PMID- 28516232
TI  - [CNS metabolism in high-risk drug abuse, German version : Insights gained from 1H
      and 31P MRS and PET].
AB  - BACKGROUND: High-risk drug consumption is a considerable problem for public
      health actors in industrialised countries. The latest trends show a market
      tendency towards diversification and increasing demand for high-purity synthetic
      drugs. Whilst most consumers seek medical help after cannabis use, it is high
      risk drugs like cocaine, heroin and amphetamines that account for most of the
      1000 drug-related deaths that occur in Germany every year. PURPOSE: This article
      presents the most prominent in vivo cerebral metabolic information in cocaine,
      heroin and methamphetamine users provided by MRI spectroscopy and PET imaging.
      MATERIALS AND METHODS: We reviewed the literature reporting neuroimaging studies
      of in vivo metabolic data for methamphetamine, cocaine and heroin consumption
      published up to March 2017. The search was conducted using PubMed with the
      following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET.
      CONCLUSION: MRI and PET are indispensable tools in gauging brain metabolic
      response to illegal drug abuse. Future breakthroughs in this field will most
      likely come from the investigation of novel neurotransmitter systems in PET and
      imaging phosphorus and carbon metabolites in MRI.

PMID- 28516233
TI  - Medical Image Data and Datasets in the Era of Machine Learning-Whitepaper from
      the 2016 C-MIMI Meeting Dataset Session.
AB  - At the first annual Conference on Machine Intelligence in Medical Imaging (C
      MIMI), held in September 2016, a conference session on medical image data and
      datasets for machine learning identified multiple issues. The common theme from
      attendees was that everyone participating in medical image evaluation with
      machine learning is data starved. There is an urgent need to find better ways to
      collect, annotate, and reuse medical imaging data. Unique domain issues with
      medical image datasets require further study, development, and dissemination of
      best practices and standards, and a coordinated effort among medical imaging
      domain experts, medical imaging informaticists, government and industry data
      scientists, and interested commercial, academic, and government entities. High
      level attributes of reusable medical image datasets suitable to train, test,
      validate, verify, and regulate ML products should be better described. NIH and
      other government agencies should promote and, where applicable, enforce, access
      to medical image datasets. We should improve communication among medical imaging
      domain experts, medical imaging informaticists, academic clinical and basic
      science researchers, government and industry data scientists, and interested
      commercial entities.

PMID- 28516235
TI  - Clinical, imaging and genotypical features of three deceased and five surviving
      cases with ADA2 deficiency.
AB  - Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of
      autoinflammatory disorder with limited reported cases. In this paper, we have
      presented the clinico-immunological, radiological and genetic characteristics of
      five surviving and three deceased childhood-onset DADA2 patients. We aimed to
      compare surviving and deceased patients in terms of clinical features and
      treatment modalities. Moreover, we have evaluated the causes of death in our
      DADA2 subjects together with the previously reported cases. Demographic features,
      clinical characteristics, imaging findings, mutations and pharmacological
      treatments of DADA2 subjects were noted from patient records of pediatric and
      adult rheumatology clinics in a retrospective and longitudinal nature. Eight
      patients from seven families were enrolled. While five of them were surviving,
      three of them had died due to various reasons. Median age of the patients at
      disease onset and diagnosis was 7 years (range 0.5-13 years) and 14 years (range
      5-27 years), respectively. The main clinical manifestations were cutaneous
      findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8)
      and gastrointestinal involvement (5/8). All patients had increased acute phase
      reactants at presentation and also during the disease flares. Until the diagnosis
      of DADA2 was confirmed, five patients have been followed-up with the diagnosis of
      PAN: two patients both with PAN and FMF, and one patient with CAPS and
      vasculitis. Demographic, clinical, neurological features and genetic mutations
      did not differ in surviving and deceased DADA2 patients. Deceased and surviving
      subjects differed in terms of treatment modalities after the diagnosis of DADA2.
      Anti-TNF alpha treatment has been initiated in five surviving patients as soon as
      the diagnosis of DADA2 was established. However, three patients who have died
      were not able to use sufficient doses of anti-TNF alpha treatment; in one case
      due to reluctance of patient and in two cases due to establishment of the
      definite diagnosis by genetic analysis at the same time with the last fatal DADA2
      episode. Despite limited number of patients, this case series for the first time
      compares the phenotypic, genotypic and medication differences between surviving
      and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and
      lifesaving in DADA2 patients.

PMID- 28516234
TI  - Assessing long-term return to play after hip arthroscopy in football players
      evaluating risk factors for good prognosis.
AB  - PURPOSE: Groin pain is the third most common disease in football players and has
      often been associated with hip pathology such as femoroacetabular impingement and
      labral lesions. Hip arthroscopy offers possibilities of function restoration via
      minimally invasive procedures. The aim of this study is to evaluate professional
      football player's injuries and their return to play after hip arthroscopy for FAI
      and labral injuries. METHODS: Patients that underwent hip arthroscopy between
      2009 and 2014 were selected retrospectively. From this population, only
      professional soccer players competing at national level were included (Tegner
      10). Arthroscopic surgery was proposed in patients with persistent pain. All
      patients were assessed for VAS score preoperatively and at 3, 6, 12 and 24 months
      post-op. HOS (sport and DLA) and mHHS tests were performed at the same time
      periods. RESULTS: All patients were men with a mean age of 26.5 +/- 7.1 years
      old. Preoperative VAS (7.4 +/- 1.3), HOS ADL (67.7 +/- 5.5), HOS sport (37.6 +/-
      18.7) and mHHS (72.5 +/- 8.8) showed improved scores during long-term follow-up.
      Time to return to play was 10.8 months (SD +/- 4.3), with range between 4 and 20
      months. Mean follow-up was 45.4 +/- 15.6 months (range from 26 to 72 months). No
      differences were observed between non-active and active patients at final follow
      up with respect to chondral lesions, but significant differences were observed
      with reference to management of the labrum (p = 0.031), where a higher rate of
      labrectomies existed among inactive patients and a higher rate of suture among
      active patients. CONCLUSIONS: Hip arthroscopy is a safe procedure with very good
      return to play results, but for optimized return to football one should consider
      patient age at the time of surgery, the condition of the labrum and low scores on
      the Harris Hip Score (mHHS) and HOS (sport version) as predictive factors for
      poor prognosis. Level of evidence IV.

PMID- 28516236
TI  - Identification of patients at risk of non-adherence to oral antirheumatic drugs
      in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an
      ARCO sub-study.
AB  - The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to
      SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective
      study, was primarily designed to assess the percentage of patients [aged >=18
      years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence
      to prescribed subcutaneous biologicals. This paper reports data for the secondary
      objective from a subset of patients, namely to evaluate non-adherence to
      prescribed oral antirheumatic drugs in RA patients in Spain using the validated
      Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky
      Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire,
      and a questionnaire (developed and validated in Spain) on patient satisfaction
      with RA treatment and preferences. A total of 271 patients (76.7% females; mean
      age 55.6 years) were being treated with oral drugs for RA, of which 234 completed
      the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The
      proportion of non-adherence in younger patients (aged <=48 years; 37.5%) was
      double that recorded in patients aged >48 years (p = 0.006). Patients with a
      perception of lower efficacy also had a higher risk of non-adherence (p = 0.012).
      Multivariable analysis showed that younger age and male gender were independently
      associated with risk of non-adherence. There was only slight agreement between
      the CQR and Morisky-Green assessment tools (kappa coefficient = 0.186), possibly
      reflecting the fact that both questionnaires measure slightly different aspects
      of medication adherence. In conclusion, one out of five RA patients was
      identified as at risk for non-adherence with the CQR, and this was more frequent
      in younger patients and in males.

PMID- 28516239
TI  - Regulation of endogenous brakes to kidney fibrosis: turning the view upside down.

PMID- 28516238
TI  - Foot pain severity is associated with the ratio of visceral to subcutaneous fat
      mass, fat-mass index and depression in women.
AB  - Body composition and poor mental health are risk factors for developing foot
      pain, but the role of different fat deposits and psychological features related
      to chronic pain are not well understood. The aim of this study was to investigate
      the association between body composition, psychological health and foot pain.
      Eighty-eight women participated in this study: 44 with chronic, disabling foot
      pain (mean age 55.3 SD 7.0 years, BMI 29.5 SD 6.7 kg/m2), and 44 age and BMI
      matched controls. Disabling foot pain was determined from the functional
      limitation domain of the Manchester Foot Pain and Disability Index. Body
      composition was measured using dual X-ray absorptiometry and psychological health
      (catastrophisation, central sensitisation and depression) was measured using
      three validated questionnaires. Between-group analyses found that foot pain was
      not significantly associated with body composition variables, but was
      significantly associated with all psychological health measures (P < 0.001
      0.047). Within-group analyses found that the severity of foot pain was
      significantly correlated with body composition measures: fat mass (total,
      android, gynoid, and visceral), fat-mass ratios [visceral/subcutaneous (VAT/SAT),
      visceral/android], fat-mass index (FMI), and depression. In multivariable
      analysis, VAT/SAT (beta 1.27, 95% CI 0.28-2.27), FMI (beta 0.14, 95% CI 0.02
      0.25) and depression (beta 0.06, 95% CI 0.00-0.12) were independently associated
      with foot pain severity. Psychological health, not body composition, was
      associated with prevalent foot pain. For women with foot pain, VAT/SAT, FMI and
      depression were associated with severity. Further work is needed to determine if
      a reduction in fat mass reduces the severity of foot pain.

PMID- 28516237
TI  - Rheumatoid factor positivity increases all-cause and cancer mortality: a cohort
      study.
AB  - The aim of this study was to determine whether rheumatoid factor (RF) is
      associated with mortality from all-cause, cardiovascular disease (CVD), and
      cancer in the healthy adults. We recruited South Korean health check-up examinees
      without rheumatoid arthritis (RA). A cohort study was performed in 295,837
      participants presumably free of osteoarthritis or RA, and who had undergone
      health screening between 2002 and 2012 and been followed up to determine the risk
      of all-cause, CVD, and cancer-specific mortality with respect to the presence or
      titer of RF. To determine whether the participants were deceased, we used
      National Death Index death certificates. The prevalence of RF positivity (>=20
      IU/mL) was 4.4%. During 1,447,403 person-years of follow-up, 1402 participants
      died. Comparing subjects negative for RF with those positive for RF, the
      multivariable adjusted hazard ratio (HR; 95% CI) for all-cause and cancer
      mortality in subjects with RF-positivity was 1.50 (1.19-1.90) and 1.56 (1.12
      2.16), respectively. Also, all-cause and cancer mortality risk was significantly
      greater in subjects with an RF titer greater than 100 IU/mL than in those with RF
      negativity (HR = 2.68, 95% CI = 1.72-4.19; HR = 2.89, 95% CI = 1.58-5.28,
      respectively) after adjusting for multiple confounders. However, the HR for
      cardiovascular mortality was not higher in subjects with RF positivity than in
      those with RF negativity (HR = 0.98, 95% CI = 0.45-2.11). In Korean healthy
      adults, presumably without RA, RF was associated with a greater risk of all-cause
      and cancer mortality.

PMID- 28516242
TI  - Defining and understanding the relationship between professional identity and
      interprofessional responsibility: implications for educating health and social
      care students.
AB  - This paper is concerned with exploring the relationship between perceptions of
      professional identities, interprofessional education (IPE) and collaborative
      practice. It seeks to introduce the concept of interprofessional responsibility
      as both a shift in the way in which to conceptualise the professional identity of
      Health and Social Care (H&SC) staff and as a new set of practices that help to
      inform the way in which students are prepared for collaborative working. The
      presented research, undertaken as part of a Ph.D. study, is based upon semi
      structured interviews (n = 33) with H&SC staff who were recruited from both the
      United Kingdom (UK) Health Service and UK universities. Drawing upon thematic
      analysis of the data, the results of the research identified that previous
      conceptualisations of professional identity aligned to a whole profession do not
      relate to the way in which professionals perceive their identities. Senior
      professionals claimed to be more comfortable with their own professional
      identity, and with working across professional boundaries, than junior
      colleagues. Academic staff also identified that much IPE currently taught in
      universities serves the purpose of box-ticking rather than being delivered in
      meaningful way. It is proposed that the findings have implications for the way in
      which IPE is currently taught, and that adoption of the proposed concept of
      'interprofessional responsibility' may help address some of the concerns these
      findings raise.

PMID- 28516240
TI  - In vivo PET imaging of neuroinflammation in Alzheimer's disease.
AB  - Increasing evidence suggests that neuroinflammation contributes to the
      pathophysiology of many neurodegenerative diseases, especially Alzheimer's
      disease (AD). Molecular imaging by PET may be a useful tool to assess
      neuroinflammation in vivo, thus helping to decipher the complex role of
      inflammatory processes in the pathophysiology of neurodegenerative diseases and
      providing a potential means of monitoring the effect of new therapeutic
      approaches. For this objective, the main target of PET studies is the 18 kDa
      translocator protein (TSPO), as it is overexpressed by activated microglia. In
      the present review, we describe the most widely used PET tracers targeting the
      TSPO, the methodological issues in tracer quantification and summarize the
      results obtained by TSPO PET imaging in AD, as well as in neurodegenerative
      disorders associated with AD, in psychiatric disorders and ageing. We also
      briefly describe alternative PET targets and imaging modalities to study
      neuroinflammation. Lastly, we question the meaning of PET imaging data in the
      context of a highly complex and multifaceted role of neuroinflammation in
      neurodegenerative diseases. This overview leads to the conclusion that PET
      imaging of neuroinflammation is a promising way of deciphering the enigma of the
      pathophysiology of AD and of monitoring the effect of new therapies.

PMID- 28516243
TI  - Clinical characteristics, risk factors and long-term outcome of 114 patients with
      folliculotropic mycosis fungoides.
AB  - Folliculotropic mycosis fungoides (FMF) is a distinct variant of mycosis
      fungoides (MF) where atypical T-cells invade the hair follicles. The objective
      was to assess the clinical features, risk factors for progression, long-term
      outcome and response to treatment modalities in a large cohort of FMF patients.
      We, therefore, conducted a single-center retrospective study, reviewing 114
      patients with FMF seen from 1987 to 2015 at the cutaneous T-cell lymphoma clinic
      of the MD Anderson Cancer Center. The mean age at diagnosis of FMF was 57.1 +/-
      13.5 years. The male to female ratio was 1.2:1. MF stage IA (n = 50, 43.9%) was
      the most common diagnosed stage, followed equally by stages IB and IIB (n = 23,
      20.2%, respectively). Eighty-six patients (75.4%) suffered from pruritus.
      Concomitant hair loss was observed in 37 (32.5%) subjects. The median number of
      different treatment modalities used per patient was 4 (range 1-12). Low-dose
      radiation was beneficial in clearing therapy refractory lesions. The overall
      survival was influenced by several factors, including advanced age (>65), late
      stages and the presence of large cell transformation (LCT). Thirty-three of 113
      patients (29.2%) progressed to more advanced stages and 26 (23.0%) died, with the
      cause of death being MF in 11 (9.7%) subjects. In conclusion, patients with FMF
      have a worse overall 10-year survival rate compared with other MF variants.
      Several factors, including stage, advanced age and the presence of LCT impact
      survival. Multiple different treatment approaches may be needed to achieve a good
      clinical response and to prevent disease progression.

PMID- 28516241
TI  - Innate immunity in Alzheimer's disease: the relevance of animal models?
AB  - The mouse is one of the organisms most widely used as an animal model in
      biomedical research, due to the particular ease with which it can be handled and
      reproduced in laboratory. As a member of the mammalian class, mice share with
      humans many features regarding metabolic pathways, cell morphology and anatomy.
      However, important biological differences between mice and humans exist and must
      be taken into consideration when interpreting research results, to properly
      translate evidence from experimental studies into information that can be useful
      for human disease prevention and/or treatment. With respect to Alzheimer's
      disease (AD), much of the experimental information currently known about this
      disease has been gathered from studies using mainly mice as models. Therefore, it
      is notably important to fully characterise the differences between mice and
      humans regarding important aspects of the disease. It is now widely known that
      inflammation plays an important role in the development of AD, a role that is not
      only a response to the surrounding pathological environment, but rather seems to
      be strongly implicated in the aetiology of the disease as indicated by the
      genetic studies. This review highlights relevant differences in inflammation and
      in microglia, the innate immune cell of the brain, between mice and humans
      regarding genetics and morphology in normal ageing, and the relationship of
      microglia with AD-like pathology, the inflammatory profile, and cognition. We
      conclude that some noteworthy differences exist between mice and humans regarding
      microglial characteristics, in distribution, gene expression, and states of
      activation. This may have repercussions in the way that transgenic mice respond
      to, and influence, the AD-like pathology. However, despite these differences,
      human and mouse microglia also show similarities in morphology and behaviour,
      such that the mouse is a suitable model for studying the role of microglia, as
      long as these differences are taken into consideration when delineating new
      strategies to approach the study of neurodegenerative diseases.

PMID- 28516244
TI  - A comparison of basilar artery diameters measured by T2WI and TOF MR angiography.
AB  - PURPOSE: The purpose of our study is to compare basilar artery diameters (BAD)
      measured by T2WI to diameters measured by TOF MR angiography (MRA). By doing
      this, we hope to understand how compatible these two methodologies are with each
      other. METHODS: We used data from 100 patients (59 females, 41 males) who
      underwent a session of both T2W MRI and TOF MRA at the same time (ages between 18
      and 83). We measured BAD by both T2WI and TOF MRA in three different levels. We
      then compared these diameters measured by two different methodologies to each
      other. RESULTS: In an area between the vertebrobasilar junction and posterior
      cerebral artery, all data measured by T2WI and TOF MRA in three different levels
      were analyzed. Average diameters measured by T2WI and TOF MRA turned out to be
      79.5% correlated with each other. As a result of our mathematical model that we
      came up with through regression analysis, we calculated that measurements taken
      by T2WI on mid-pontine levels could predict TOF MRA measures with 78.3% accuracy.
      In T2WI and TOF MRA, average diameters measured were 2.982 +/- 0.4717 and 3.205
      +/- 0.4281 mm, respectively. Statistical analyses showed that images measured by
      T2W series were significantly smaller than those measured by TOF MRA (p < 0.05).
      CONCLUSION: Our study showed that BAD measured by T2WI were smaller than those
      measured by TOF MRA. We think that it will be beneficial to refer our results to
      avoid T2WI and TOF MRA mismatch when evaluating BAD.

PMID- 28516245
TI  - Municipal solid waste-derived biochar for the removal of benzene from landfill
      leachate.
AB  - The potential of biochar, produced from fibrous organic fractions of municipal
      solid waste (MSW), for remediation of benzene, one of the frequently found toxic
      volatile organic compounds in landfill leachate, was investigated in this study
      based on various environmental conditions such as varying pH, benzene
      concentration, temperature and time. At the same time, landfill leachate quality
      parameters were assessed at two different dump sites in Sri Lanka: Gohagoda and
      Kurunegala. MSW biochar (MSW-BC) was produced by slow temperature pyrolysis at
      450  degrees C, and the physiochemical characteristics of the MSW-BC were
      characterized. All the leachate samples from the MSW dump sites exceeded the
      World Health Organization permissible level for benzene (5 ug/L) in water.
      Removal of benzene was increased with increasing pH, with the highest removal
      observed at ~pH 9. The maximum adsorption capacity of 576 ug/g was reported at
      room temperature (~25  degrees C). Both Freundlich and Langmuir models fitted
      best with the equilibrium isotherm data, suggesting the involvement of both
      physisorption and chemisorption mechanisms. Thermodynamic data indicated the
      feasibility of benzene adsorption and its high favorability at higher
      temperatures. The values of [Formula: see text] suggested physical interactions
      between sorbate and sorbent, whereas kinetic data implied a significant
      contribution of chemisorption. Results obtained from FTIR provided clear evidence
      of the involvement of functional groups in biochar for benzene adsorption. This
      study suggests that MSW biochar could be a possible remedy for benzene removal
      from landfill leachate and at the same time MSW can be a potential source to
      produce biochar which acts as a prospective material to remediate its pollutants
      while reducing the volume of waste.

PMID- 28516247
TI  - Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in
      cryopreserved human hepatocytes.
AB  - Genetic polymorphisms in human N-acetyltransferase 2 (NAT2) modify the metabolism
      of numerous drugs and carcinogens. These genetic polymorphisms modify both drug
      efficacy and toxicity and cancer risk associated with carcinogen exposure.
      Previous studies have suggested phenotypic heterogeneity among different NAT2
      slow acetylator genotypes. NAT2 phenotype was investigated in vitro and in situ
      in samples of human hepatocytes obtained from various NAT2 slow and intermediate
      NAT2 acetylator genotypes. NAT2 gene dose response (NAT2*5B/*5B > NAT2*5B/*6A >
      NAT2*6A/*6A) was observed towards the N-acetylation of the NAT2-specific drug
      sulfamethazine by human hepatocytes both in vitro and in situ. N-acetylation of 4
      aminobiphenyl, an arylamine carcinogen substrate for both N-acetyltransferase 1
      and NAT2, showed the same trend both in vitro and in situ although the
      differences were not significant (p > 0.05). The N-acetylation of the N
      acetyltransferase 1-specific substrate p-aminobenzoic acid did not follow this
      trend. In comparisons of NAT2 intermediate acetylator genotypes, differences in N
      acetylation between NAT2*4/*5B and NAT2*4/*6B hepatocytes were not observed in
      vitro or in situ towards any of these substrates. These results further support
      phenotypic heterogeneity among NAT2 slow acetylator genotypes, consistent with
      differential risks of drug failure or toxicity and cancer associated with
      carcinogen exposure.

PMID- 28516248
TI  - Environmental toxicants, incidence of degenerative diseases, and therapies from
      the epigenetic point of view.
AB  - Epigenotoxicology is an emerging field of study that investigates the non
      genotoxic epigenetic effects of environmental toxicants resulting in alteration
      of normal gene expression and disruption of cell function. Recent findings on the
      role of toxicant-induced epigenetic modifications in the development of
      degenerative diseases have opened up a promising research direction to explore
      epigenetic therapy approaches and related prognostic biomarkers. In this review,
      we presented comprehensive data on epigenetic alterations identified in various
      diseases, including cancer, autoimmune disorders, pulmonary conditions as well as
      cardiovascular, gastrointestinal and bone disease. Although data on abnormalities
      of DNA methylation and their role in the development of diseases are abundant,
      less is known about the impact of histone modifications and microRNA expressions.
      Further, we discussed the effects of selected common environmental toxicants on
      epigenetic modifications and their association with particular abnormalities. A
      number of different environmental toxicants have been identified for their role
      in aberrant DNA methylation, histone modifications, and microRNA expression. Such
      epigenetic effects were shown to be tissue-type specific and highly associated
      with the level and duration of exposure. Finally, we described present and future
      therapeutic strategies, including medicines and dietary compounds for combating
      the toxicant-induced epigenetic alterations. There are currently seven histone
      deacetylase inhibitors and two DNA methyltransferase inhibitors approved for
      clinical use and many other promising candidates are in preclinical and clinical
      testing. Dietary compounds are thought to be the effective and safe strategies
      for treating and prevention of epigenetic pathophysiological conditions. Still
      more concentrated epigenetic researches are required for evaluation of chemical
      toxicity and identifying the causal association between key epigenetic alteration
      and disease.

PMID- 28516249
TI  - [A 67-year-old man with fever, night sweat and ascites].
AB  - A 67-year-old man presented with fever, night sweat and abdominal complaints for
      about 4 weeks. Ultrasound and a computed tomography scan showed distinct ascites
      as the main finding, presenting as exsudate with predominating lymphoid cells.
      Because of long-term immunosuppressive therapy with the tumor necrosis factor
      (TNF)-alpha inhibitor golimumab for psoriasis, the suspicion for a possible
      tuberculous peritonitis arose. This was confirmed with an enzyme-linked
      immunospot assay, a high level of adenosine deaminase in the ascites and a
      peritoneum which was studded with multiple whitish nodules, corresponding to
      granulomas with giant cells. With a standard antituberculous regimen the symptoms
      were quickly relieved and finally complete restitution was achieved.

PMID- 28516246
TI  - Aspergillus Species in Bronchiectasis: Challenges in the Cystic Fibrosis and Non
      cystic Fibrosis Airways.
AB  - Bronchiectasis is a chronic irreversible airway abnormality associated with
      infectious agents that either cause or superinfect the airways. While the role of
      bacteria is well studied, much remains to be determined about fungi in both
      cystic fibrosis- and non-cystic fibrosis-related bronchiectasis. The airway is
      constantly exposed to inhaled ambient moulds of which Aspergillus represent the
      most ubiquitous. In a normal healthy host, this situation is of little
      consequence. The presence of anatomical or immunological abnormalities such as
      those in bronchiectasis leads to a range of fungal-related pathologies from
      asymptomatic airway colonization to fungal sensitization, allergic
      bronchopulmonary aspergillosis or chronic pulmonary aspergillosis. These entities
      are difficult to recognize, diagnose and treat due in part to a lack of validated
      biomarkers. Our true understanding of the complex relationships that regulate
      fungal-host interactions is still in its infancy and, several questions remain.
      This includes if fungal epidemiology in bronchiectasis is uniform across
      countries, and to what extent immunopathological mechanisms-related to fungal
      airway infections-occurs in different disease states. Specific triggers to
      allergic or infectious responses to Aspergillus require further exploration. How
      transition occurs between allergic and invasive phenotypes and their respective
      biomarkers is also important. Whether anti-fungal treatment is warranted in all
      cases and what the optimal management strategy is, particularly when treatment
      should commence and its expected duration remains unclear. Further research is
      clearly necessary and should be prioritized to better understand the clinical
      effects and impact of Aspergillus in the setting of bronchiectasis.

PMID- 28516250
TI  - [Choosing wisely recommendations in angiology].
AB  - BACKGROUND: The Choosing wisely initiative addresses measures of high medical
      impact which are frequently not appropriately performed according to expert
      opinion. OBJECTIVE: To increase the quality of indications by providing
      supportive information on diagnostic and therapeutic measures in the field of
      angiology. MATERIALS AND METHODS: As part of the Choosing wisely initiative, the
      German Society of Angiology has constructed five positive recommendations on
      underused measures and five negative recommendations concerning those possibly
      overused. The recommendations were validated by the twelve professional societies
      of the German Society of Internal Medicine in a consensus conference. RESULTS AND
      DISCUSSION: The recommendations cover a broad spectrum of diagnostic and
      therapeutic modalities, such as the role of ultrasound examinations in vascular
      diseases, screening for abdominal aortic aneurysms, diagnosis and therapy of
      peripheral artery disease (PAD), investigation of chronic ulcers, therapy of
      varicosis, and finally, the problems associated with using anticoagulants in PAD
      or thrombosis. By discussing the evidence, we aim to demonstrate that not all
      medically possible measures are actually appropriate in every situation.

PMID- 28516251
TI  - [Severe hypertriglyceridemia : Diagnostics and new treatment principles].
AB  - Severe hypertriglyceridemia is defined at a plasma triglyceride (TG)
      concentration of >885 mg/dl and may result - in particular when clinical symptoms
      appear before the age of 40 - from "large variant" mutations in genes which
      influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary
      factors have to be excluded and treated before further genetic tests are
      considered. Typical symptoms in almost all patients are recurrent, sometimes
      severe abdominal pain attacks, which can result in acute pancreatitis, the most
      important, sometimes life-threatening complication. To minimize the risk of
      severe pancreatitis, the aim is to maintain the plasma TG concentration <1000
      mg/dl. Other clinical manifestations which can occur and are reversible are
      eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, dyspnea syndrome, and
      impaired neurocognitive function. The hyperviscosity syndrome caused by
      chylomicronemia is seen as the underlying reason for some of the symptoms.
      Patients with mild-to-moderate hypertriglyceridemia have an increased
      cardiovascular risk. To lower this is the primary treatment goal here. Treatment
      mainly consists of a life-long, strict fat- and carbohydrate-restricted diet and
      the abstention from alcohol. Omega-3-Fatty acids and fibrates can be used to
      lower plasma TG levels. Recently, new gene therapy approaches for LPL-deficient
      patients have become available in Germany.

PMID- 28516252
TI  - Chronic eccentric arm cycling improves maximum upper-body strength and power.
AB  - INTRODUCTION: Eccentric leg cycling (cycle ergometry adapted to impose muscle
      lengthening contractions) offers an effective exercise for restoring lower-body
      muscular function, maintaining health, and improving performance in clinical and
      athletic populations. PURPOSE: We extended this model to the upper body and
      evaluated the effectiveness of a 7-week eccentric arm cycling (ECCarm)
      intervention to improve upper-body muscular function. We also explored whether
      ECCarm would alter arterial function. METHODS: Participants performed ECCarm (n =
      9) or concentric arm cycling (CONarm; n = 8) 3*/week while training intensity
      increased (5-20 min, 60-70% upper-body peak heart rate). Maximum elbow extensor
      strength, upper-body concentric power, and peripheral and central arterial
      stiffness were assessed before and after training. RESULTS: During training,
      heart rates and perceived exertion did not differ between groups (~68% upper-body
      peak heart rate, ~12 Borg units, both P > 0.05), whereas power during ECCarm was
      ~2* that for CONarm (122 +/- 43 vs. 59 +/- 20 W, P < 0.01). Muscle soreness for
      ECCarm was greater than CONarm (P = 0.02), however, soreness was minimal for both
      groups (<0.50 cm). Following training, ECCarm exhibited greater changes in elbow
      extensor strength (16 +/- 10 vs. 1 +/- 9%, P = 0.01) and upper-body power (6 +/-
      8 vs. -3 +/- 7%, P < 0.01) compared to CONarm. Peripheral and central arterial
      stiffness did not change for either group (both P > 0.05). CONCLUSION: Upper-body
      eccentric exercise improved dynamic muscular function while training at low
      exertion levels. Results occurred with minimal soreness and without compromising
      arterial function. ECCarm findings parallel eccentric leg cycling findings and
      indicate that eccentric cycle ergometry offers a robust model for enhancing upper
      body muscular function. ECCarm could have applications in rehabilitation and
      sport training.

PMID- 28516254
TI  - Use of Muscular Cholinesterase of Astyanax bifasciatus (Teleostei, Characidae) as
      a Biomarker in Biomonitoring of Rural Streams.
AB  - Cholinesterase (ChE) activity was measured in Astyanax bifasciatus maintained in
      controlled conditions. Muscle ChE activity of individuals collected in field
      conditions in two seasons was compared among specimens collected in seven streams
      (forest and rural) of the lower Iguacu river basin in association with physical,
      chemical, pesticides and biological factors. Significant differences in muscle
      ChE activity between control fish and fish collected in streams in both seasons
      were found, with higher activity in natural conditions. This the first time that
      differences in muscle ChE activity have been found among fish collected from
      different streams, suggesting synergism among multiple factors (e.g. temperature,
      pH, animal weight) and ecological attributes (richness and abundance) as
      influencing the variation in biomarkers. It is necessary to evaluate the quality
      of aquatic environments for a more accurate biomonitoring approach.

PMID- 28516253
TI  - Comparison of the effects of three different Baccaurea angulata whole fruit juice
      doses on plasma, aorta and liver MDA levels, antioxidant enzymes and total
      antioxidant capacity.
AB  - PURPOSE: Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is
      a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice
      showed that it possesses antioxidant properties. Therefore, further work is
      needed to confirm the efficacy and proper dosage of B. angulata as a potential
      natural antioxidant. The present study was thus carried out to compare the
      effects of three different B. angulata whole fruit (WF) juice doses administered
      at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver
      malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase,
      glutathione peroxidase and catalase) as well as total antioxidant capacity in
      rabbits fed high-cholesterol diet. METHODS: Thirty-five male rabbits of New
      Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was
      fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50
      ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00
      ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50
      ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1
      was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was
      fed standard pellet and 1.00 ml/kg/day B. angulata WF juice. RESULTS: The three
      doses reduced the formation of MDA and enhanced the expression of endogenous
      antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as
      the most potent. CONCLUSION: Higher doses of B. angulata juice exerted better
      antioxidant activity.

PMID- 28516255
TI  - Water Quality Interaction with Alkaline Phosphatase in the Ganga River:
      Implications for River Health.
AB  - Carbon, nitrogen and phosphorus inputs through atmospheric deposition, surface
      runoff and point sources were measured in the Ganga River along a gradient of
      increasing human pressure. Productivity variables (chlorophyll a, gross primary
      productivity, biogenic silica and autotrophic index) and heterotrophy
      (respiration, substrate induced respiration, biological oxygen demand and
      fluorescein diacetate hydrolysis) showed positive relationships with these
      inputs. Alkaline phosphatase (AP), however, showed an opposite trend. Because AP
      is negatively influenced by available P, and eutrophy generates a feedback on P
      fertilization, the study implies that the alkaline phosphatase can be used as a
      high quality criterion for assessing river health.

PMID- 28516257
TI  - [Plant-derived contaminants in food : Occurrence, effects and risk assessment].
AB  - Among the various contaminants, the group of natural plant-derived substances in
      the modern food chain has been generating increasing concern in recent years. The
      adverse effects encountered may be diverse and pose risks of acute, subchronic or
      chronic toxicity. The underlying mechanisms of toxicity may be thresholded or be
      based on interactions with DNA, as for genotoxic carcinogens, for which the
      existence of a threshold cannot be assumed. This article gives an overview of the
      major plant-derived contaminants of present concern in the modern food chain and
      describes their mode of action and adverse effects.

PMID- 28516256
TI  - [Skin diseases associated with environmental factors].
AB  - BACKGROUND: Multiple environmental exposures may derange the regulatory and
      repair mechanisms of the skin and lead to dermatological disease. OBJECTIVES:
      Provide an overview of non-allergic skin diseases associated with environmental
      factors. MATERIALS AND METHODS: Review of current scientific evidence for
      associations of non-allergic skin diseases with environmental exposures:
      irritation, chemicals, infection, UV-radiation, temperature. RESULTS:
      Predisposition (constitution e. g. for atopic dermatitis, psoriasis and filaggrin
      gene mutations) and exposure (environment) are crucial for disease development or
      maintenance of health in an individual. Specific chemical and contagious agents
      lead to characteristic skin diseases (e. g. halogen acne) which under certain
      conditions may be recognized as occupational disease. The most frequent cause for
      irritant contact dermatitis is water (wet work). Natural optical radiation of
      different wavelength may cause light-induced inflammatory skin diseases.
      Phototoxic reactions due to psoralens, furocoumarins and drugs are frequent. The
      polymorphous light eruption is not an exogenous delayed type allergy, but seems
      to be a reaction against a UV-induced neoantigen of the skin. UVB exhibits direct
      mutagenic effects on DNA. Sun exposure and defective DNA-repair mechanisms are
      risk factors for skin tumors. Heat/cold exposure under specific conditions also
      triggers skin diseases (primary: congelations, frostbite, heat burn, scalding,
      chronic-inducible urticaria; secondary: deterioration of preexisting inflammatory
      diseases (e. g. systemic sclerosis)). CONCLUSIONS: To keep the skin healthy, an
      early identification and elimination of harmful environmental factors and
      treatment of early disease stages is necessary. This requires strategies of
      environmental prevention and behavioral prevention, as well as global action (e.
      g. with regard to increasing incidence of skin cancer).

PMID- 28516258
TI  - [Biomarkers of internal exposure to toxicologically relevant contaminants in
      food].
AB  - The assessment of health risks resulting from the intake of genotoxic carcinogens
      in food depends essentially on a valid exposure assessment. The reliability of
      the external exposure estimation is restricted by various factors, e. g.
      inaccurate data from dietary protocols and variations of food contaminant
      contents. As an alternative, the individual internal exposure to genotoxic
      substances may be described by specific biomarkers in different matrices. For
      example, mercapturic acids formed after glutathione conjugation of electrophilic
      metabolites can be detected in the urine. This typically reflects the exposure to
      the parent compound over a period of one to two days. The determination of
      adducts in the blood proteins serum albumin (SA) and hemoglobin (Hb) allows for
      conclusions to be drawn about the external exposure within the last three weeks
      (SA) or within the last four months (Hb). Protein adducts are used routinely in
      occupational medicine as biomarkers of internal exposure to substances in the
      ambient air of the workplace. The availability of increasingly sensitive
      analytical techniques also makes it possible to detect numerous adducts in
      proteins from human blood samples that are formed after the continuous intake of
      very small doses of toxic substances from foods. Here, we present the current
      state of science exemplified by protein adducts of the food contaminants
      acrylamide, aflatoxin B1 and glycidol. The biomarker can be used in the future to
      investigate previously unknown relationships between internal exposure and
      disease incidences.

PMID- 28516259
TI  - [Poisoning caused by marine biotoxins].
AB  - This paper presents a short summary of the knowledge on marine biotoxins. As
      toxins are known for their acute effects, they have been classified here
      according to the effects they cause in acute human poisoning incidents. Toxins
      may thus be distinguished into those that affect the nervous system (paralytic
      and other neurotoxins), memory (amnesic poisons), and the digestive system
      (diarrhetic toxins). Furthermore, newly emerging toxins, such as ciguatoxins or
      shark toxins, and factors that lead to the introduction of toxins in new areas,
      are presented. Relevant suggestions for further reading are given.

PMID- 28516260
TI  - [Dietary exposure assessment of substances in foods : The BfR MEAL study - the
      first German total diet study].
AB  - The dietary exposure of a population to chemical substances is estimated based on
      representative consumption data and data on the occurrence of substances in
      foods. Consumption data in Germany for different age groups are provided by the
      National Nutrition Survey ll, VELS, EsKiMo and the ongoing KiESEL study. The data
      for the levels of substances in foods is currently obtained from the German food
      monitoring programme (Lebensmittel-Monitoring) and the German Food Composition
      Table (Bundeslebensmittelschlussel) and is not sufficient for a comprehensive
      evaluation of dietary exposure in Germany. More data is needed and, in
      particular, the range of analysed substances should be broadened to reduce the
      uncertainties of the exposure assessment. A representative data basis for
      concentrations of substances in foods will be established with the first German
      total diet study, called the BfR MEAL study. The study will markedly reduce major
      uncertainties in the dietary exposure assessment through its wide coverage of
      substances in food groups, the inclusion of prepared foods, the orientation on
      low measurement limits as well as the analysis of substances without a reliable
      data basis.

PMID- 28516261
TI  - [Metals and their compounds as contaminants in food : Arsenic, cadmium, lead and
      aluminum].
AB  - Metals and their compounds are ubiquitously distributed in the environment, thus
      reaching plant and animal derived food. While actual exposure levels in Europe do
      not give rise to concern for acute toxicity, chronic toxicity of some metals and
      metalloids cannot be completely ruled out. Thus, in the case of inorganic
      arsenic, an elevated risk of carcinogenicity in different organs cannot be
      excluded even under actual dietary exposure conditions. In the case of cadmium,
      nephrotoxicity may be a particular problem for certain subgroups, such as
      children. Regarding lead, exposure levels have dropped considerably during the
      last two decades; nevertheless, developmental neurotoxicity may still be a
      problem during prenatal development and early childhood. Also in the case of
      aluminum current dietary exposure levels are close to the tolerable weekly intake
      (TWI) value derived by the European Food Safety Authority (EFSA). Taken together,
      for all four examples, further reductions in exposure levels are required.

PMID- 28516262
TI  - [Nanomaterials in foodstuffs - toxicological properties and risk assessment].
AB  - Nanomaterials measure below 100 nm in size in at least one dimension. In general,
      organic and inorganic nanoparticles can be distinguished. In addition, nanosized
      structures may differ substantially with regard to their shape, chemical
      composition and physical properties. They may originate either from natural
      processes or can be manufactured intentionally. The possible specific
      toxicological properties of nanoparticles that might be based on their enhanced
      reactivity due to an increased surface-to-volume ratio, as compared to larger
      particles, or which might result from preferential uptake in cells and tissues,
      are the subject of current toxicological research. Consumers are exposed to
      nanomaterials via the oral route by foodstuffs containing naturally formed,
      unknowingly incorporated or intentionally added nanoparticles. In the course of
      this work, an overview of the occurrence of nanomaterials in foodstuffs,
      including the legal definition and labeling requirements, will be given.
      Furthermore, specific characteristics of the oral uptake of nanomaterials will be
      presented alongside challenges for experimental investigation of gastrointestinal
      uptake and the effects of nanoscaled particles. These will be discussed in
      relation to potentially relevant toxicological properties and modes of action.
      Despite a plethora of available experimental studies, there are still knowledge
      gaps with regard to the exposure against orally ingested nanoparticles and with
      regard to possible toxicological consequences of such particles in order to allow
      for accurate risk assessment of the materials in foodstuffs and food packaging.

PMID- 28516263
TI  - [Social inequalities in the prevalence of chronic back pain among adults in
      Germany].
AB  - BACKGROUND: Back pain is a common cause for health care utilization and inability
      to work and associated with corresponding costs. The aim of the study was to
      investigate socioeconomic inequalities in chronic back pain in the adult general
      population. METHODS: The analyses were based on pooled data of three waves (2009,
      2010, 2012) of the nationwide German Health Update (GEDA) study carried out by
      the Robert Koch Institute (n = 62,606 aged 18 years and older). Self-reported
      back pain symptoms persisting at least three months were used to determine
      lifetime and 12-month prevalence. For analyzing socioeconomic differences in the
      prevalence of chronic back pain, a multidimensional SES index and its three
      individual components - educational level, occupational status and income - were
      used. RESULTS: About every sixth man (17.1%) and every fourth woman (24.4%)
      reported chronic back pain in the past twelve months. With decreasing SES, the 12
      month prevalence of chronic back pain increased (Relative Index of Inequality
      (RII) [95% CI], men = 2.29 [2.04-2,56], women=1.92 [1.76-2.09]). Similar results
      were observed for lifetime prevalence. For both men and women, educational level,
      occupational status and income each had independent effects on chronic back pain
      prevalence. CONCLUSION: In Germany, back pain is widely prevalent. Our finding
      that different aspects of SES are independently associated with chronic back pain
      prevalence is a challenge but also a chance for treatment and preventive
      strategies combining behavioral and setting-oriented measures.

PMID- 28516264
TI  - A Response to Commentaries on "Beyond Sexual Orientation: Integrating Gender/Sex
      and Diverse Partnered Sexualities via Sexual Configurations Theory" (van Anders,
      2015).

PMID- 28516265
TI  - The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and
      prevention.
AB  - Vitamin D deficiency and insufficiency is a global health issue that afflicts
      more than one billion children and adults worldwide. The consequences of vitamin
      D deficiency cannot be under estimated. There has been an association of vitamin
      D deficiency with a myriad of acute and chronic illnesses including preeclampsia,
      childhood dental caries, periodontitis, autoimmune disorders, infectious
      diseases, cardiovascular disease, deadly cancers, type 2 diabetes and
      neurological disorders. This review is to put into perspective the controversy
      surrounding the definition for vitamin D deficiency and insufficiency as well as
      providing guidance for how to treat and prevent vitamin D deficiency.

PMID- 28516268
TI  - GPNA inhibits the sodium-independent transport system L for neutral amino acids.
AB  - L-gamma-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine
      transporter ASCT2, although it is known that it also inhibits other sodium
      dependent amino acid transporters. In a panel of human cancer cell lines, which
      express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium
      independent influx of leucine and glutamine. The kinetics of the effect suggests
      that GPNA is a low affinity, competitive inhibitor of system L transporters. In
      Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but
      not ASCT2 silencing, lowers the cell content of leucine. Under the same
      conditions the activity of mTORC1 is inhibited. Decreased cell content of
      branched chain amino acids and mTORC1 inhibition are observed in most of the
      other cell lines upon incubation with GPNA. It is concluded that GPNA hinders the
      uptake of essential amino acids through system L transporters and lowers their
      cell content.

PMID- 28516269
TI  - beta-Alanine intercede metabolic recovery for amelioration of human cervical and
      renal tumors.
AB  - beta-Alanine is a non-essential amino acid and presents as a major component of
      various sports supplements. It is a non-proteogenic amino acid, formed in vivo by
      degradation of carnosine, anserine, balenine, and dihydrouracil. The present
      study was aimed at investigating the anti-tumor effects of beta-alanine in renal
      and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis
      were used to measure cell viability. Lactate dehydrogenase (LDH) expression was
      analyzed using FITC-conjugated fluorescent antibody. The cellular adenosine
      triphosphate (ATP) content was measured using bioluminescence method. Cell
      migration was determined by the simple standard-scratch method. beta-Alanine
      reduced renal and cervical cell growth significantly. Percentage of inhibition of
      renal and cervical tumor cells was increased at higher concentration of beta
      alanine. LDH expression and ATP content were significantly reduced in renal and
      cervical tumor cells in a dose-dependent manner. Renal and cervical tumor cell
      migration were significantly reduced following 10 and 100 mM of beta-alanine
      treatment. In our study, beta-alanine exerts no significant effect on normal MDCK
      cells except a marginal effect at the highest concentration (100 mM). In summary,
      our experimental data suggest that beta-alanine may be a potential anti-tumor
      agent exhibiting several anti-cancer effects in renal and cervical tumor cells.

PMID- 28516266
TI  - Constitutive calcium entry and cancer: updated views and insights.
AB  - Tight control of basal cytosolic Ca2+ concentration is essential for cell
      survival and to fine-tune Ca2+-dependent cell functions. A way to control this
      basal cytosolic Ca2+ concentration is to regulate membrane Ca2+ channels
      including store-operated Ca2+ channels and secondary messenger-operated channels
      linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or
      without its reticular STIM partner and Transient Receptor Potential (TRP)
      proteins, were considered to be the main Ca2+ channels involved. It is well
      accepted that, in response to cell stimulation, opening of these Ca2+ channels
      contributes to Ca2+ entry and the transient increase in cytosolic Ca2+
      concentration involved in intracellular signaling. However, in various
      experimental conditions, Ca2+ entry and/or Ca2+ currents can be recorded at rest,
      without application of any experimental stimulation. This led to the proposition
      that some plasma membrane Ca2+ channels are already open/activated in basal
      condition, contributing therefore to constitutive Ca2+ entry. This article
      focuses on direct and indirect observations supporting constitutive activity of
      channels belonging to the Orai and TRP families and on the mechanisms underlying
      their basal/constitutive activities.

PMID- 28516267
TI  - Methods of Candida dubliniensis identification and its occurrence in human
      clinical material.
AB  - Candida dubliniensis was reported as a new species in 1995. This species is often
      misidentified as Candida albicans. The aims of this work were to determine the
      occurrence of C. dubliniensis in various clinical materials, to evaluate several
      ways to identify it and to examine the genetic variability of isolates. Among
      7706 isolates originally identified as C. albicans, 237 were identified as C.
      dubliniensis (3.1%). Most of the C. dubliniensis isolates were obtained from the
      upper and lower respiratory tract (61.4 and 22.9%). Five phenotypic methods
      including latex agglutination were used (cultivation on CHROMagar Candida, on
      Staib agar, at 42  degrees C and in medium with 6.5% NaCl), but only cultivation
      on the medium with an increased concentration of NaCl and latex agglutination
      gave reliable results. Species-specific polymerase chain reaction was used as the
      confirmation method. Matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry provided less reliable results. In fact, 78.9% of C.
      dubliniensis isolates had scores above 1.7. However, the rest of them (21.1%)
      were also identified as C. dubliniensis even when the scores were lower than 1.7.
      Divergences among C. dubliniensis strains were evaluated by means of pulsed-field
      gel electrophoresis. Eighty-six selected C. dubliniensis isolates showed a 69.6%
      level of similarity. The results of this study expand the knowledge of the
      incidence, means of identification and genotypic divergence of C. dubliniensis
      isolates.

PMID- 28516270
TI  - [Ocular sarcoidosis].
AB  - Ocular manifestation of sarcoidosis occurs in up to 60% of patients with
      confirmed systemic sarcoidosis and represents one of the most common forms of
      noninfectious uveitis. In known pulmonary sarcoidosis, ocular involvement can
      occur in up to 80% of cases. Sarcoidosis can also present only in the eye,
      without a systemic manifestation (ocular sarcoidosis). Typically, ocular
      sarcoidosis shows bilateral granulomatous uveitis and can involve all parts of
      the eye. Apart from an acute anterior uveitis, chronic intermediate or posterior
      uveitis can be found. In order to prevent a severe reduction of visual acuity
      leading to blindness, early diagnosis and treatment is essential. For diagnosis,
      specific clinical signs involving the eye (bilateral granulomatous changes in all
      parts of the eye) and typical laboratory investigations (angiotensin-converting
      enzyme, ACE; lysozyme; soluble interleukin 2 receptor, sIL2R; chest X-ray; chest
      CT) have to be taken into account, since biopsy to prove noncaseating granulomas
      is not performed with changes restricted to the eye due to the high risk of
      vision loss. Ocular sarcoidosis mostly responds well to local or systemic steroid
      treatment. If the therapeutic effect is insufficient, immunosuppressive agents
      and biologics can be applied.

PMID- 28516272
TI  - Uterine Artery Embolization for Symptomatic Adenomyosis: 7-Year Clinical Follow
      up Using UFS-Qol Questionnaire.
AB  - PURPOSE: The purpose of this study was to assess clinical outcomes 7 years after
      uterine artery embolization (UAE) in the treatment of symptomatic adenomyosis.
      MATERIALS AND METHODS: In this prospective cohort study, one specialized hospital
      in the Netherlands recruited patients with symptomatic adenomyosis or adenomyosis
      in combination with fibroids for UAE. The 7-year post-intervention outcomes were
      health-related quality of life (HRQOL), symptom severity scores (SSS),
      satisfaction, menopause and re-interventions. RESULTS: Twenty-nine patients with
      adenomyosis (15 with fibroids) were treated with UAE between September 2006 and
      January 2010. The 7-year questionnaire was mailed in November 2016. The mean
      follow-up was 95 months (SD 9.0) at a mean age of 50 (SD 5.4). Questionnaires
      were returned by 24/29 patients (83%). The remaining five patients were contacted
      through telephone. One of these patients was untraceable. Seven years after
      treatment 5 of 28 patients (18%) underwent a secondary hysterectomy. The HRQOL
      and SSS scores as measured by UFS-QOL at 3 months after UAE showed significant
      improvement of -57 points (score: 15) and +40 points (score: 91), respectively.
      These scores remained comparable stable up unto 7 years. The SSS showed a
      significant difference of 17 points (0-100) in favor of the adenomyosis in
      combination with fibroids group (p = 0.020). Menopause was reported by 10/28
      patients (36%). Twenty-one of 29 (72%) patients declared to be at least fairly
      satisfied about UAE. CONCLUSIONS: After 7 years of follow-up, in 82% of UAE
      treated patients with symptomatic adenomyosis a hysterectomy was avoided.

PMID- 28516271
TI  - Three-dimensional Image Fusion Guidance for Transjugular Intrahepatic
      Portosystemic Shunt Placement.
AB  - INTRODUCTION: To assess the safety, feasibility and effectiveness of image fusion
      guidance with pre-procedural portal phase computed tomography with
      intraprocedural fluoroscopy for transjugular intrahepatic portosystemic shunt
      (TIPS) placement. MATERIALS AND METHODS: All consecutive cirrhotic patients
      presenting at our interventional unit for TIPS creation from January 2015 to
      January 2016 were prospectively enrolled. Procedures were performed under general
      anesthesia in an interventional suite equipped with flat panel detector, cone
      beam computed tomography (CBCT) and image fusion technique. All TIPSs were placed
      under image fusion guidance. After hepatic vein catheterization, an unenhanced
      CBCT acquisition was performed and co-registered with the pre-procedural portal
      phase CT images. A virtual path between hepatic vein and portal branch was made
      using the virtual needle path trajectory software. Subsequently, the 3D virtual
      path was overlaid on 2D fluoroscopy for guidance during portal branch
      cannulation. Safety, feasibility, effectiveness and per-procedural data were
      evaluated. RESULTS: Sixteen patients (12 males; median age 56 years) were
      included. Procedures were technically feasible in 15 of the 16 patients (94%).
      One procedure was aborted due to hepatic vein catheterization failure related to
      severe liver distortion. No periprocedural complications occurred within 48 h of
      the procedure. The median dose-area product was 91 Gy cm2, fluoroscopy time 15
      min, procedure time 40 min and contrast media consumption 65 mL. Clinical benefit
      of the TIPS placement was observed in nine patients (56%). CONCLUSION: This study
      suggests that 3D image fusion guidance for TIPS is feasible, safe and effective.
      By identifying virtual needle path, CBCT enables real-time multiplanar guidance
      and may facilitate TIPS placement.

PMID- 28516274
TI  - Evaluation of a New Esophageal Stent for the Treatment of Malignant and Benign
      Esophageal Strictures.
AB  - PURPOSE: To evaluate the efficacy and safety of the EGIS esophageal stent for
      treating malignant and benign esophageal strictures. MATERIALS AND METHODS: Data
      of 73 patients (mean age 63.0 +/- 11.9 years; 66 males) with malignant esophageal
      stricture and 16 patients (mean age 63.7 +/- 9.5 years; 13 males) with benign
      esophageal stricture who received the EGIS esophageal stent (S&G Biotech,
      Seongnam, Korea) between October 2010 and April 2016 were obtained from a
      prospectively maintained electronic database. RESULTS: Technical and clinical
      success rates were 100% (89/89). Stent malfunction (i.e., tumor/tissue
      overgrowth, stent migration, and food impaction) occurred in 20.5% (15/73) and
      37.5% (6/16) of patients with malignant and benign esophageal strictures,
      respectively. Stent migration occurred in five (6.8%) and four (25%) patients
      with malignant and benign esophageal strictures, respectively. The median follow
      up durations in patients with malignant and benign esophageal strictures were 130
      [interquartile range (IQR) 76-322] days and 486 (IQR 315-736) days, respectively.
      Recurrent dysphagia occurred in 14.1% (10/73) and 87.5% (14/16) of patients with
      malignant and benign esophageal strictures, respectively. The median recurrence
      free durations in patients with malignant and benign esophageal strictures were
      126 (IQR 69-259) days and 100 (IQR 40-182) days, respectively. CONCLUSION: The
      EGIS esophageal stent appears to be effective for malignant esophageal
      strictures, with relatively low rate of stent migration, whereas, for benign
      esophageal strictures, it seems to be associated with a high rate of recurrent
      dysphagia, mainly due to stent migration.

PMID- 28516273
TI  - A Comparative Study of Ablation Boundary Sharpness After Percutaneous
      Radiofrequency, Cryo-, Microwave, and Irreversible Electroporation Ablation in
      Normal Swine Liver and Kidneys.
AB  - PURPOSE: To compare ablation boundary sharpness after percutaneous radiofrequency
      ablation (RFA), cryoablation (CA), microwave ablation (MWA) and irreversible
      electroporation (IRE) ablation in normal swine liver and kidney. MATERIALS AND
      METHODS: Percutaneous CT-guided RFA (n = 5), CA (n = 5), MWA (n = 5) and IRE (n =
      5) were performed in the liver and kidney of four Yorkshire pigs. Parameters were
      chosen to produce ablations 2-3 cm in diameter with a single ablation probe.
      Contrast-enhanced CT imaging was performed 24 h after ablation, and animals were
      killed. Treated organs were removed and processed for histologic analysis with
      hematoxylin and eosin, and terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL). Three readers independently analyzed CT, H&E and TUNEL stained
      images of the ablation boundary to delineate regions of (1) viable cells, (2)
      complete necrosis or (3) mixture of viable and necrotic cells which was defined
      as the transition zone (TZ). The width of TZ was compared across the techniques
      and organs. RESULTS: Ablations appeared as non-contrast-enhancing regions on CT
      with sharp transition to enhancing normal tissue. On TUNEL stained slides, the
      mean width (MUm) of the TZ after MWA was 319 +/- 157 in liver and 267 +/- 95 in
      kidney, which was significantly lower than RFA (811 +/- 477 and 938 +/- 429); CA
      (452 +/- 222 and 700 +/- 563); and IRE (1319 +/- 682 and 1570 +/- 962) (all p <
      0.01). No significant differences were observed between the organs. CONCLUSION:
      Under similar conditions, the width of the TZ at the ablation boundary varies
      significantly between different ablation techniques.

PMID- 28516275
TI  - The Role of Cardiac Biomarkers in Pregnancy.
AB  - OPINION STATEMENT: Cardiovascular disease (CVD) is the leading cause of pregnancy
      associated mortality, with an increasingly complex pregnant population. While our
      understanding of CVD in pregnancy continues to evolve, there remains a need to
      develop widely accessible tools to follow pregnant women both with and without
      preexisting disease with respect to cardiovascular risk, particularly for those
      presenting with symptoms suggestive of cardiovascular pathology. Thus, research
      is emerging with respect to the potential role of novel and established cardiac
      biomarkers in diagnosing and following CVD in pregnancy. Here, we review the
      normal hemodynamics of pregnancy and the behavior of various biomarkers in both
      normal and complicated pregnancies.

PMID- 28516277
TI  - Analysis of cellular autofluorescence in touch samples by flow cytometry:
      implications for front end separation of trace mixture evidence.
AB  - The goal of this study was to survey optical and biochemical variation in cell
      populations deposited onto a surface through touch or contact and identify
      specific features that may be used to distinguish and then sort cell populations
      from separate contributors in a trace biological mixture. Although we were not
      able to detect meaningful biochemical variation in touch samples deposited by
      different contributors through preliminary antibody surveys, we did observe
      distinct differences in red autofluorescence emissions (650-670 nm), with as much
      as a tenfold difference in mean fluorescence intensities observed between certain
      pairs of donors. Results indicate that the level of red autofluorescence in touch
      samples can be influenced by a donor's contact with specific material prior to
      handling the substrate from which cells were collected. In particular, we
      observed increased red autofluorescence in cells deposited subsequent to handling
      laboratory gloves, plant material, and certain types of marker ink, which could
      be easily visualized microscopically or using flow cytometry, and persisted after
      hand washing. To test whether these observed optical differences could
      potentially be used as the basis for a cell separation workflow, a controlled two
      person touch mixture was separated into two fractions via fluorescence-activated
      cell sorting (FACS) using gating criteria based on intensity of 650-670 nm
      emissions and then subjected to DNA analysis. Genetic analysis of the sorted
      fractions provided partial DNA profiles that were consistent with separation of
      individual contributors from the mixture suggesting that variation in
      autofluorescence signatures, even if driven by extrinsic factors, may nonetheless
      be a useful means of isolating contributors to some touch mixtures. Graphical
      Abstract Conceptual workflow diagram. Trace biological mixtures containing cells
      from multiple individuals are analyzed by flow cytometry. Cells are then
      physically separated into two populations based on intensity of red
      autofluorescence using Fluorescence Activated Cell Sorting. Each isolated cell
      fraction is subjected to DNA analysis resulting in a DNA profile for each
      contributor.

PMID- 28516276
TI  - P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein
      induced ATP release in neuroblastoma SH-SY5Y cells.
AB  - Abnormalities of alpha-synuclein (ASN), the main component of protein deposits
      (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy
      bodies, Alzheimer's disease, and other neurodegenerative disorders. These
      alterations include increase in the levels of soluble ASN oligomers in the
      extracellular space. Numerous works have identified several mechanisms of their
      toxicity, including stimulation of the microglial P2X7 receptor leading to
      oxidative stress. While the significant role of purinergic signaling
      particularly, P2 family receptors-in neurodegenerative disorders is well known,
      the interaction of extracellular soluble ASN with neuronal purinergic receptors
      is yet to be studied. Therefore, in this study, we have investigated the effect
      of ASN on P2 purinergic receptors and ATP-dependent signaling. We used
      neuroblastoma SH-SY5Y cell line and rat synaptoneurosomes treated with exogenous
      soluble ASN. The experiments were performed using spectrofluorometric,
      radiochemical, and immunochemical methods. We found the following: (i) ASN
      induced intracellular free calcium mobilization in neuronal cells and nerve
      endings depends on the activation of purinergic P2X7 receptors; (ii) activation
      of P2X7 receptors leads to pannexin 1 recruitment to form an active complex
      responsible for ATP release; and (iii) ASN greatly decreases the activity of
      extracellular ecto-ATPase responsible for ATP degradation. Thus, it is concluded
      that purinergic receptors might be putative pharmacological targets in the
      molecular mechanism of extracellular ASN toxicity. Interference with P2X7
      signaling seems to be a promising strategy for the prevention or therapy of PD
      and other neurodegenerative disorders.

PMID- 28516280
TI  - Optimization of an ultrasound-assisted derivatization for GC/MS analysis of
      oxygenated organic species in atmospheric aerosol.
AB  - A novel ultrasound-assisted derivatization followed by GC/MS analysis was
      developed for the quantification of oxygenated organic species in ambient
      aerosol. Derivatization parameters mostly influencing the analytical response
      were investigated, i.e., solvent type, reagent concentration, and reaction
      duration. Response surface methodology was used to design experiments and a
      quadratic model was utilized to predict the variables and establish the optimal
      conditions. The study was performed on standard solutions of 30 compounds
      representing the major classes of oxygenated compounds typically found in ambient
      aerosol, i.e., low molecular weight carboxylic acids, sugars, and phenols. In
      comparison with conventional methods, the optimized procedure uses mild reaction
      temperature (room temperature instead of 70  degrees C), reduces the amount of
      silyl reagent (24 vs. 40 MUL), and shortens derivatization times (45 vs. 70 min),
      participating in the current trend of analytical chemistry towards clean, green
      methods that reduce costs and decrease pollution. Once optimized, the ultrasound
      procedure was validated by assessing for repeatability, linearity, detection
      limits, and derivative stability. For all oxygenated organic species, the
      proposed method showed a good reproducibility-as the relative standard deviations
      (RSDs%, n = 5) of intra-day analysis were <=7% - a good linearity with the
      correlation coefficients of calibration curves R 2 >= 99.8, and low detection
      limits, ranging from 0.34 to 6.50 ng MUL-1; thus it is suitable for its
      applicability in air quality monitoring. Finally, this method was successfully
      applied to determine 30 oxygenated organic species in three ambient PM2.5 samples
      collected at an urban site in Northern Italy in three different seasons.
      Graphical abstract Ultrasound-assisted derivatization is a green alternative
      method for GC/MS analysis of oxygenated organic species in atmospheric aerosol
      towards reduction of energy and reactive consumption.

PMID- 28516279
TI  - A new carbon-based magnetic material for the dispersive solid-phase extraction of
      UV filters from water samples before liquid chromatography-tandem mass
      spectrometry analysis.
AB  - Magnetic solid-phase extraction is one of the most promising new extraction
      methods for liquid samples before ultra-high-performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) analysis. Several types of materials,
      including carbonaceous ones, have been prepared for this purpose. In this paper,
      for the first time, the preparation, characterization, and sorption capability of
      Fe3O4-graphitized carbon black (mGCB) composite toward some compounds of
      environmental interest were investigated. The synthesized mGCB consisted of
      micrometric GCB particles with 55 m2 g-1 surface area bearing some carbonyl and
      hydroxyl functionalities and the surface partially decorated by Fe3O4
      microparticles. The prepared mGCB was firstly tested as an adsorbent for the
      extraction from surface water of 50 pollutants, including estrogens,
      perfluoroalkyl compounds, UV filters, and quinolones. The material showed good
      affinity to many of the tested compounds, except carboxylates and glucoronates;
      however, some compounds were difficult to desorb. Ten UV filters belonging to the
      chemical classes of benzophenones and p-aminobenzoates were selected, and
      parameters were optimized for the extraction of these compounds from surface
      water before UHPLC-MS/MS determination. Then, the method was validated in terms
      of linearity, trueness, intra-laboratory precision, and detection and
      quantification limits. In summary, the method performance (trueness, expressed as
      analytical recovery, 85-114%; RSD 5-15%) appears suitable for the determination
      of the selected compounds at the level of 10-100 ng L-1, with detection limits in
      the range of 1-5 ng L-1. Finally, the new method was compared with a published
      one, based on conventional solid-phase extraction with GCB, showing similar
      performance in real sample analysis. Graphical Abstract Workflow of the
      analytical method based on magnetic solid-phase extraction followed by LC-MS/MS
      determination.

PMID- 28516278
TI  - Molecularly imprinted polymers based stir bar sorptive extraction for
      determination of cefaclor and cefalexin in environmental water.
AB  - Although stir bar sportive extraction was thought to be a highly efficiency and
      simple pretreatment approach, its wide application was limited by low
      selectivity, short service life, and relatively high cost. In order to improve
      the performance of the stir bar, molecular imprinted polymers and magnetic carbon
      nanotubes were combined in the present study. In addition, two monomers were
      utilized to intensify the selectivity of molecularly imprinted polymers. Fourier
      transform infrared spectroscopy, scanning electron microscopy, and selectivity
      experiments showed that the molecularly imprinted polymeric stir bar was
      successfully prepared. Then micro-extraction based on the obtained stir bar was
      coupled with HPLC for determination of trace cefaclor and cefalexin in
      environmental water. This approach had the advantages of stir bar sportive
      extraction, high selectivity of molecular imprinted polymers, and high sorption
      efficiency of carbon nanotubes. To utilize this pretreatment approach, pH,
      extraction time, stirring speed, elution solvent, and elution time were
      optimized. The LOD and LOQ of cefaclor were found to be 3.5 ng . mL-1 and 12.0 ng
      . mL-1, respectively; the LOD and LOQ of cefalexin were found to be 3.0 ng . mL-1
      and 10.0 ng . mL-1, respectively. The recoveries of cefaclor and cefalexin were
      86.5 ~ 98.6%. The within-run precision and between-run precision were acceptable
      (relative standard deviation <7%). Even when utilized in more than 14 cycles, the
      performance of the stir bar did not decrease dramatically. This demonstrated that
      the molecularly imprinted polymeric stir bar based micro-extraction was a
      convenient, efficient, low-cost, and a specific method for enrichment of cefaclor
      and cefalexin in environmental samples.

PMID- 28516281
TI  - ToF-SIMS study of differentiation of human bone-derived stromal cells: new
      insights into osteoporosis.
AB  - Lipids have numerous important functions in the human body, as they form the
      cells' plasma membranes and play a key role in many disease states, presumably
      also in osteoporosis. Here, the fatty acid composition of the outer plasma
      membranes of cells differentiated into the osteogenic and adipogenic direction is
      studied with surface-sensitive time-of-flight secondary ion mass spectrometry
      (ToF-SIMS). For data evaluation, principal component analysis (PCA) is applied.
      Human (bone-derived) mesenchymal stromal cells (hMSCs) from an osteoporotic donor
      and a control donor are compared to reveal differences in the fatty acid
      composition of the membranes. The chemical information is correlated to staining
      and real-time quantitative polymerase chain reaction (rt-qPCR) results to provide
      insight into the gene expression of several differentiation markers on the RNA
      level. Adipogenic differentiation of hMSCs from a non-osteoporotic donor
      correlates with increased relative intensities of all fatty acids under
      investigation. After osteogenic differentiation of non-osteoporotic cells, the
      relative mass signal intensities of unsaturated fatty acids such as oleic and
      linoleic acids are increased. However, the osteoporotic cells show increased
      levels of palmitic acid in the plasma membrane after exposure to osteogenic
      differentiation conditions, which correlates to an immature differentiation state
      relative to non-osteoporotic osteogenic cells. This immature differentiation
      state is confirmed by increased early osteogenic differentiation factor Runx2 on
      RNA level and by less calcium mineralization spots seen in von Kossa staining and
      ToF-SIMS images. Graphical abstract Time-of-flight secondary ion mass
      spectrometry is applied to analyze the fatty acid composition of the outer plasma
      membranes of cells differentiated into the adipogenic and osteogenic direction.
      Cells from an osteoporotic and a control donor are compared to reveal differences
      due to differentiation and disease stage of the cells.

PMID- 28516282
TI  - Region-Specific Iron Measured by MRI as a Biomarker for Parkinson's Disease.
AB  - The identification of sensitive and specific biomarkers for Parkinson's disease
      (PD) poses an important clinical challenge. A potential biomarker for early
      diagnosis and disease monitoring of PD is region-specific iron. Iron accumulation
      in the substantia nigra pars compacta is considered a main characteristic of PD.
      However, questions remain, such as the relationship between nigral iron and
      clinical indices of PD (motor impairment or disease duration). Further, previous
      studies have suggested the influence of iron on other nuclei. Iron quantification
      using magnetic resonance imaging (MRI) allows for studies of the relationship
      between regional iron and clinical symptoms in vivo. Thus, in this review we
      discuss the following topics: the technological development of MRI in measuring
      brain iron, nigral iron as a potential marker for PD in both clinical and
      prodromal stages, other influences of regional iron on PD, and clinical
      translation and future perspectives.

PMID- 28516283
TI  - Developmental window of sensorineural deafness in biotinidase-deficient mice.
AB  - Biotinidase deficiency is an autosomal recessively inherited disorder that
      results in the inability to recycle the vitamin, biotin. If untreated, the
      disorder can result in a range of neurological and cutaneous symptoms, including
      sensorineural deficits and deafness. To understand early mechanistic
      abnormalities that may precede more generalized and nonspecific effects of
      metabolic deficits such as weight loss and acidosis, we have analyzed auditory
      brainstem responses (ABRs) in biotinidase-deficient knockout (Btd -/- ) mice in
      the periweaning period with or without dietary biotin supplementation. We find
      significant increases in the latency of wave V of the ABR elicited by pure tone
      stimuli at one octave intervals, which precede substantial increases in ABR
      thresholds. Finer interpeak latency analyses of these changes indicate they are
      confined to the latter ABR waves associated with the CNS and likely reflect
      slowed brainstem transmission time. In contrast, peripheral nervous system
      conduction velocity appears normal. Further, we find that biotin-supplementation
      after the onset of symptoms reverses the latency shifts, which has significant
      relevance for early treatment in patients. Finally, ABR latencies in Btd -/- mice
      fed a biotin-supplemented diet for the first month of life appear refractory to
      transmission time slowing during a subsequent bout of biotin deficiency. These
      data suggest a transient vulnerability window for biotin deficiency in the
      auditory brainstem. Finally, we also observe a developmental vulnerability window
      involving follicular melanosome production or melanocyte survival. Sensorineural
      deafness precedes peripheral hearing loss in developmental biotinidase deficiency
      and is transient if rescued by dietary biotin within a short developmental
      window.

PMID- 28516285
TI  - Intracellular morphological changes in Staphylococcus aureus induced by treatment
      with sodium hypochlorite.
AB  - Sodium hypochlorite (NaOCl) is commonly used as a disinfectant; however, its
      bactericidal mechanism has not yet been clarified. In the present study, the
      bactericidal mechanism of NaOCl was examined using microscopy and gel
      electrophoresis techniques with Staphylococcus aureus strain 209P. S. aureus
      cells treated with 500 and 1000 ppm NaOCl for 5 and 15 min were observed by SEM
      and TEM. SEM images of the bacterial cells treated with NaOCl showed an irregular
      surface, with cells being partially invaginated. TEM images of the bacterial
      cells showed cytoplasmic alterations, accompanied by a partially irregular
      cellular surface. Under a fluorescence microscope, we clearly observed
      fluorescence quenching in the 1000 ppm NaOCl-treated cells. Based on these
      observations, which indicated that NaOCl damaged chromosomal DNA, we next
      extracted chromosomal DNA from bacterial cells treated with NaOCl and performed
      agarose gel electrophoresis. Chromosomal DNA was absent in the DNA sample from
      the bacterial cells treated with 500 ppm NaOCl. From these biochemical results,
      it was strongly suggested that NaOCl degrades the chromosomal DNA of S. aureus.
      We consider that the morphological changes in the cytoplasm induced by NaOCl may
      be related to NaOCl-induced degradation of S. aureus chromosomal DNA.

PMID- 28516284
TI  - Short-chain acyl-CoA dehydrogenase deficiency: from gene to cell pathology and
      possible disease mechanisms.
AB  - Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an inherited disorder of
      mitochondrial fatty acid oxidation that is characterized by the presence of
      increased butyrylcarnitine and ethylmalonic acid (EMA) concentrations in plasma
      and urine. Individuals with symptomatic SCADD may show relatively severe
      phenotype, while the majority of those who are diagnosed through newborn
      screening by tandem mass spectrometry may remain asymptomatic. As such, the
      associated clinical symptoms are very diverse, ranging from severe metabolic or
      neuromuscular disabilities to asymptomatic. Molecular analysis of affected
      individuals has identified rare gene variants along with two common gene
      variants, c.511C > T and c.625G > A. In vitro studies have demonstrated that the
      common variants as well as the great majority of rare variants, which are
      missense variants, impair folding, that may lead to toxic accumulation of the
      encoded protein, and/or metabolites, and initiate excessive production of ROS and
      chronic oxidative stress. It has been suggested that this cell toxicity in
      combination with yet unknown factors can trigger disease development. This
      association and the full implications of SCADD are not commonly appreciated.
      Accordingly, there is a worldwide discussion of the relationship of clinical
      manifestation to SCADD, and whether SCAD gene variants are disease associated at
      all. Therefore, SCADD is not part of the newborn screening programs in most
      countries, and consequently many patients with SCAD gene variants do not get a
      diagnosis and the possibilities to be followed up during development.

PMID- 28516287
TI  - Spread of poxviruses in livestock in Brazil associated with cases of double and
      triple infection.
AB  - The objective of this work is to describe the distribution of outbreaks of
      vaccinia virus (VACV), pseudocowpox virus (PCPV), and bovine papular stomatitis
      virus (BSPV) in Brazil. The Official Laboratory of the Brazilian Ministry of
      Agriculture received 89 samples from different locations in Brazil in 2015 and
      2016 for diagnosis of vesicular and exanthematous disease. Poxvirus coinfections
      occurred in 11 out of 33 outbreaks, including the first reported triple infection
      by BPSV, PCPV, and VACV. This occurrence may be associated with the circulation
      of these viruses in Brazilian cattle.

PMID- 28516286
TI  - Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine
      tumor.
AB  - Neuroendocrine tumors are rare, and little is known about the existence of cancer
      stem cells in this disease. Identification of the tumorigenic population will
      contribute to the development of effective therapies targeting neuroendocrine
      tumors. Surgically resected brain metastases from a primary neuroendocrine tumor
      of unknown origin were dissociated and cultured in serum-free neurosphere medium.
      Stem cell properties, including self-renewal, differentiation potential, and stem
      cell marker expression, were examined. Tumor formation was evaluated using
      intracranial xenograft models. The effect of temozolomide was measured in vitro
      by cell viability assays. We established the neuroendocrine tumor sphere cell
      line ANI-27S, which displayed stable exponential growth, virtually unlimited
      expansion in vitro, and expression of stem-cell markers such as CD133, nestin,
      Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and
      nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the
      neuroendocrine markers synaptophysin and chromogranin A. Intracranial
      xenotransplanted brain tumors recapitulated the original patient tumor and
      temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first
      time, we demonstrated the presence of a sphere-forming, stem cell-like population
      in brain metastases from a primary neuroendocrine tumor. We also demonstrated the
      potential therapeutic effects of temozolomide for this disease.

PMID- 28516288
TI  - Efficacy and Safety of Ibuprofen in Infants Aged Between 3 and 6 Months.
AB  - Ibuprofen is a non-steroidal anti-inflammatory drug frequently administered to
      children of various ages for relief of fever and pain and is approved as an over
      the-counter medication in many countries worldwide. Although there are extensive
      data on its efficacy and safety in children and adults, there are divergent
      dosing recommendations for analgesia and treatment of fever in infants,
      especially in the age group between 3 and 6 months of age. In this article, we
      have assessed the safety and efficacy of ibuprofen use in infants in an attempt
      to find the optimal method of pain and fever management in this specific age
      group. Based on the current evidence, short-term use of ibuprofen is considered
      safe in infants older than 3 months of age having a body weight above 5-6 kg when
      special attention is given to the hydration of the patient. Ibuprofen should be
      prescribed based on body weight using a dose of 5-10 mg/kg. This dose can be
      administered 3-4 times a day resulting in a maximum total daily dose of 30-40
      mg/kg. The rectal route has been shown to be less reliable because of erratic
      absorption, especially in young infants. Since most efficacy and safety data have
      been derived from trials in infants with fever, future studies should focus on
      the efficacy of ibuprofen in young infants with pain.

PMID- 28516289
TI  - Understanding the Stability of Dopamine and Dobutamine Over 24 h in Simulated
      Neonatal Ward Conditions.
AB  - OBJECTIVES: Our objectives were to investigate the possible effects of
      temperature and light on the stability of dopamine and dobutamine continuous
      infusions over 24 h when prepared in a variety of dilution vehicles. METHODS:
      Syringe-driver infusion apparatuses were set up for dopamine and dobutamine
      diluted with either 0.9% sodium chloride (NaCl) or 5% glucose delivering 3 and 5
      MUg/kg/min, respectively, via 206-cm extension sets. All infusions were prepared
      for a neonate weight of 1 kg. Infusions were run over 24 h with approximately
      half the tubing within an incubator set at 35  degrees C. Cyclic voltammetry was
      used to monitor the concentration of the inotrope within the syringe and at the
      end of the extension set, both initially and after 24 h. RESULTS: The variation
      in the concentration of dopamine and dobutamine in the vials (n = 6) was 3.58 and
      1.22%, respectively. This variation increased to 10.88% for dopamine and 5.76%
      for dobutamine in the syringe. After 24 h, a significant reduction in the
      concentration of dopamine was observed at the end of the extension set when
      prepared in 0.9% NaCl versus 5% glucose (p < 0.001; n = 6-7) and in dobutamine
      when prepared in 0.9% NaCl (p < 0.001; n = 6-7). No differences in the
      concentration of dopamine prepared in 0.9% NaCl were observed after 24 h in light
      exposed and light-protected extension sets (n = 6-7). CONCLUSIONS: Dobutamine is
      more stable in dilution vehicles than dopamine, and inotropes are more stable in
      the 5% glucose dilution vehicle than in 0.9% NaCl. Such findings will provide
      guidance on the choice of inotropes.

PMID- 28516290
TI  - Comparison of Long-Term Outcomes After Non-curative Endoscopic Resection in Older
      Patients with Early Gastric Cancer.
AB  - BACKGROUND: Limited data exist that describe the long-term outcomes from
      additional surgery following non-curative endoscopic resection (ER) of early
      gastric cancer (EGC) in older people. This study aimed to determine the
      appropriate treatment strategy for these patients. METHODS: We analyzed data from
      2895 patients who underwent ER for EGC, of whom 451 (15.6%) had non-curative
      resections followed by curative surgery or surveillance only. Of these patients,
      138 were older (aged >=70 years). We compared the long-term outcomes of the
      different treatment strategies in the older patients with non-curative resections
      for EGC, and the outcomes of each treatment strategy, with those in younger
      patients. RESULTS: The older patients underwent curative resections, non-curative
      resections with surgery, or non-curative resections with surveillance, and the 5
      year disease-specific survival (DSS) rates were 100, 100, and 73%, respectively.
      There was a trend toward significance for DSS in favor of the non-curative
      resections with surgery group compared with the non-curative resections with
      surveillance-only group (p = 0.069). Among those who did not undergo additional
      surgery, the older patients had worse DSS than the younger patients, and patients
      who underwent additional surgery had better DSS, irrespective of their ages.
      Multivariable analysis adjusted for other-cause mortality generated similar
      results. Overall survival and recurrence-free survival did not differ according
      to treatment strategy, and perioperative morbidity and mortality did not differ
      significantly according to age. CONCLUSIONS: In older patients with non
      curatively resected EGC, additional surgery demonstrated a trend toward better
      DSS, and perioperative complications did not increase significantly.

PMID- 28516291
TI  - Downstaging in Stage IV Pancreatic Cancer: A New Population Eligible for Surgery?
AB  - BACKGROUND: Recent papers consider surgery as an option for synchronous liver
      oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)].
      In this study, we present our series of resected mPDACs after neoadjuvant
      chemotherapy (nCT). PATIENTS AND METHODS: All patients resected after downstaging
      of mPDAC were included in this study. Downstaging criteria were disappearance of
      liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and
      duration of nCT, last nCT surgery interval, histology, morbidity, and mortality
      were recorded, and overall survival (OS) and disease-free survival (DFS) were
      analyzed. RESULTS: Overall, 24 of 535 patients (4.5%) observed with mPDAC were
      included. These patients received gemcitabine alone (5/24), gemcitabine +
      nanoparticle albumin-bound (nab)-paclitaxel (3/24), and FOLFIRINOX (16/24).
      Primary tumor size decreased from 31 to 19 mm (p < 0.001), and serum CA19-9
      decreased from 596 to 18 U/mL (p < 0.001). In 14/24 patients, the tumor was
      located in the head. Median interval nCT surgery was 2 months, there were no
      mortalities, and the postoperative course was uneventful in 34% of cases. Grade
      B/C pancreatic fistula, postoperative bleeding, and sepsis occurred in 17/4, 4,
      and 12% of cases, respectively, and reoperation rate was 4%. R0 resection was
      achieved in 88% of cases, with 17% complete pathological response. Positive nodes
      were found in 9/24 patients with a median node ratio of 0.37, and OS and DFS was
      56 and 27 months, respectively. CONCLUSIONS: Patients with mPDAC who were fully
      responsive to nCT may be cautiously considered for surgery, with potential
      benefit in survival compared with palliative chemotherapy alone. This is
      supported by results of our retrospective study, which is the largest ever
      reported.

PMID- 28516292
TI  - LiMAx Test Improves Diagnosis of Chemotherapy-Associated Liver Injury Before
      Resection of Colorectal Liver Metastases.
AB  - BACKGROUND: Chemotherapy of colorectal liver metastases (CLMs) prior to liver
      resection implies the risk of chemotherapy-associated liver injury, leading to
      increased postoperative morbidity and mortality OBJECTIVE: The aim of this study
      was to evaluate the LiMAx (liver maximum capacity) test for diagnosis of
      chemotherapy-associated liver injury. METHODS: This was a retrospective analysis
      of patients with CLMs, prior to liver resection. We performed preoperative
      assessment of liver function using biochemical parameters and the LiMAx test. The
      individual history of chemotherapy within 12 months, including regimen, number of
      cycles, and therapy-free interval were collected, and histopathological
      evaluation of tumor-free liver tissue was performed in resected patients.
      RESULTS: A total of 204 patients were included, of whom 127 (62%) had received
      previous chemotherapy. The LiMAx test was worse after chemotherapy (340 +/- 95
      vs. 391 +/- 82 ug/kg/h; p < 0.001). Impaired LiMAx results (<315 ug/kg/h) were
      determined in 49% of patients after chemotherapy, and no effects of chemotherapy,
      liver steatosis or fibrosis on biochemical parameters were observed. LiMAx
      impairment was dependent on the number of oxaliplatin cycles, the therapy-free
      interval, and obesity in multivariate analysis. In addition, the LiMAx test was
      worse in patients with relevant steatosis, fibrosis and steatohepatitis. Patients
      with an impaired LiMAx showed sufficient regeneration during chemotherapy
      cessation when surgery was postponed (272 +/- 57 - 348 +/- 72 ug/kg/h; p =
      0.003). CONCLUSION: The LiMAx test enables non-invasive preoperative diagnosis of
      chemotherapy-associated liver injury. Preoperative performance of the LiMAx test
      can augment surgical strategy and timing of surgery after previous chemotherapy,
      thus avoiding increased postoperative morbidity.

PMID- 28516294
TI  - Does seeing an Asian face make speech sound more accented?
AB  - Prior studies have reported that seeing an Asian face makes American English
      sound more accented. The current study investigates whether this effect is
      perceptual, or if it instead occurs at a later decision stage. We first
      replicated the finding that showing static Asian and Caucasian faces can shift
      people's reports about the accentedness of speech accompanying the pictures. When
      we changed the static pictures to dubbed videos, reducing the demand
      characteristics, the shift in reported accentedness largely disappeared. By
      including unambiguous items along with the original ambiguous items, we
      introduced a contrast bias and actually reversed the shift, with the Asian-face
      videos yielding lower judgments of accentedness than the Caucasian-face videos.
      By changing to a mixed rather than blocked design, so that the ethnicity of the
      videos varied from trial to trial, we eliminated the difference in accentedness
      rating. Finally, we tested participants' perception of accented speech using the
      selective adaptation paradigm. After establishing that an auditory-only accented
      adaptor shifted the perception of how accented test words are, we found that no
      such adaptation effect occurred when the adapting sounds relied on visual
      information (Asian vs. Caucasian videos) to influence the accentedness of an
      ambiguous auditory adaptor. Collectively, the results demonstrate that visual
      information can affect the interpretation, but not the perception, of accented
      speech.

PMID- 28516295
TI  - Judgments of differences and ratios of subjective heaviness.
AB  - Experimental instructions to judge differences or ratios of subjective heaviness
      numerically are generally assumed to produce judgments linearly proportional to
      the respective heaviness differences or heaviness ratios. In this study,
      participants were instructed to numerically judge the difference or ratio of
      heaviness between two weights being lifted separately, either unimanually or
      bimanually. Weight values were combined factorially. Patterns of factorial curves
      revealed that unimanual lifting triggered linear judgments of heaviness
      differences, whereas bimanual lifting triggered nonlinear judgments of heaviness
      ratios. Lifting conditions produced these judgments independently of the
      instruction specifications to judge differences or ratios. These results suggest
      the interpretation that unimanual lifting triggers linear judgments of heaviness
      differences by default, whereas bimanual lifting triggers nonlinear judgments of
      heaviness ratios learned through experience. Implications for sensory measurement
      are noted.

PMID- 28516293
TI  - The dominant allele Aft induces a shift from flavonol to anthocyanin production
      in response to UV-B radiation in tomato fruit.
AB  - MAIN CONCLUSION: The introgression of the A ft allele into domesticated tomato
      induced a shift from flavonol to anthocyanin production in response to UV-B
      radiation, while the hp - 1 allele negatively influenced the response of
      flavonoid biosynthesis to UV-B. Introgression of the dominant allele Anthocyanin
      fruit (Aft) from Solanum chilense induces anthocyanin accumulation in the peel of
      tomato (Solanum lycopersicum L.) fruit. UV-B radiation can influence plant
      secondary metabolism regulating the expression of several genes, among which
      those involved in flavonoid biosynthesis. Here, we investigated whether post
      harvest UV-B treatment could up-regulate flavonoid production in tomato fruits
      and whether the Aft allele could affect flavonoid biosynthesis under UV-B
      radiation. Mature green fruits of an anthocyanin-rich tomato mutant line (SA206)
      and of its wild-type reference, cv. Roma, were daily subjected to post-harvest UV
      B treatment until full ripening. Up-regulation of CHS and CHI transcription by UV
      B treatment induced flavonoid accumulation in the peel of cv. Roma. Conversely,
      UV-B decreased the total flavonoid content and CHS transcript levels in the SA206
      peel. SA206 being a double mutant containing also hp-1 allele, we investigated
      also the behavior of hp-1 fruit. The decreased peel flavonoid accumulation and
      gene transcription in response to UV-B suggest that hp-1 allele is involved in
      the marked down-regulation of the flavonoid biosynthesis observed in SA206 fruit.
      Interestingly, in SA206, UV-B radiation promoted the synthesis of delphinidin,
      petunidin, and malvidin by increasing F3'5'H and DFR transcription, but it
      decreased rutin production, suggesting a switch from flavonols to anthocyanins.
      Finally, although UV-B radiation does not reach the inner fruit tissues, it down
      regulated flavonoid biosynthesis in the flesh of both genotypes. This study
      provides, for the first time, evidence that the presence of the functional Aft
      allele, under UV-B radiation, redirects flavonoid synthesis towards anthocyanin
      production and suggests that the hp-1 allele negatively influences the response
      of flavonoid biosynthesis to UV-B.

PMID- 28516296
TI  - Substrate-Coated Illumination Droplet Spray Ionization: Real-Time Monitoring of
      Photocatalytic Reactions.
AB  - Real-time monitoring of photocatalytic reactions facilitates the elucidation of
      the mechanisms of the reactions. However, suitable tools for real-time monitoring
      are lacking. Herein, a novel method based on droplet spray ionization named
      substrate-coated illumination droplet spray ionization (SCI-DSI) for direct
      analysis of photocatalytic reaction solution is reported. SCI-DSI addresses many
      of the analytical limitations of electrospray ionization (ESI) for analysis of
      photocatalytic-reaction intermediates, and has potential for both in situ
      analysis and real-time monitoring of photocatalytic reactions. In SCI-DSI-mass
      spectrometry (MS), a photocatalytic reaction occurs by loading sample solutions
      onto the substrate-coated cover slip and by applying UV light above the modified
      slip; one corner of this slip adjacent to the inlet of a mass spectrometer is the
      high-electric-field location for launching a charged-droplet spray. After both
      testing and optimizing the performance of SCI-DSI, the value of this method for
      in situ analysis and real-time monitoring of photocatalytic reactions was
      demonstrated by the removal of cyclophosphamide (CP) in TiO2/UV. Reaction times
      ranged from seconds to minutes, and the proposed reaction intermediates were
      captured and identified by tandem mass spectrometry. Moreover, the free hydroxyl
      radical (.OH) was identified as the main radicals for CP removal. These results
      show that SCI-DSI is suitable for in situ analysis and real-time monitoring of CP
      removal under TiO2-based photocatalytic reactions. SCI-DSI is also a potential
      tool for in situ analysis and real-time assessment of the roles of radicals
      during CP removal under TiO2-based photocatalytic reactions.Graphical Abstract.

PMID- 28516299
TI  - IPCAI 2017 Special Issue: Information Processing for Computer-Assisted
      Interventions, 8th International Conference 2017-Part 1.

PMID- 28516297
TI  - Subcritical Water Hydrolysis of Peptides: Amino Acid Side-Chain Modifications.
AB  - Previously we have shown that subcritical water may be used as an alternative to
      enzymatic digestion in the proteolysis of proteins for bottom-up proteomics.
      Subcritical water hydrolysis of proteins was shown to result in protein sequence
      coverages greater than or equal to that obtained following digestion with
      trypsin; however, the percentage of peptide spectral matches for the samples
      treated with trypsin were consistently greater than for those treated with
      subcritical water. This observation suggests that in addition to cleavage of the
      peptide bond, subcritical water treatment results in other hydrolysis products,
      possibly due to modifications of amino acid side chains. Here, a model peptide
      comprising all common amino acid residues (VQSIKCADFLHYMENPTWGR) and two further
      model peptides (VCFQYMDRGDR and VQSIKADFLHYENPTWGR) were treated with subcritical
      water with the aim of probing any induced amino acid side-chain modifications.
      The hydrolysis products were analyzed by direct infusion electrospray tandem mass
      spectrometry, either collision-induced dissociation or electron transfer
      dissociation, and liquid chromatography collision-induced dissociation tandem
      mass spectrometry. The results show preferential oxidation of cysteine to
      sulfinic and sulfonic acid, and oxidation of methionine. In the absence of
      cysteine and methionine, oxidation of tryptophan was observed. In addition, water
      loss from aspartic acid and C-terminal amidation were observed in harsher
      subcritical water conditions. Graphical Abstract ?.

PMID- 28516298
TI  - Modeled traffic noise at the residence and colorectal cancer incidence: a cohort
      study.
AB  - PURPOSE: Traffic noise has become an increasing public health concern, associated
      with pervasive negative health effects, most likely through pathways of sleep
      disruption and stress. Both sleep disruption and stress have been associated with
      colorectal cancer. The purpose of this study was to investigate the association
      between residential traffic noise and colorectal cancer incidence. METHODS:
      Traffic noise was calculated for all residential addresses from 1987 to 2012 for
      51,283 Danes in the Diet, Cancer and Health Cohort. We used Cox proportional
      hazard models to investigate the association between residential traffic noise 5
      and 10 years before diagnosis, and overall colorectal cancer incidence, as well
      as subtypes (rectal, proximal, and distal colon). Hazard ratios (HRs) were
      calculated as crude and adjusted for potential confounders. RESULTS: During
      follow-up, 1,134 colorectal cancers developed (737 colon, 397 rectal). We found
      no association between residential road traffic noise and rectal cancer. We
      observed an association with distal colon cancer: HR 1.18, 95% CI 1.00-1.40, but
      not for proximal colon cancer: 0.99 (0.83-1.18), per 10 dB, 10 years preceding
      diagnosis. There was no association between railway noise and colorectal cancer,
      or any subtype. CONCLUSION: The present study suggested that long-term exposure
      to residential road traffic noise might increase the risk for colon cancer,
      especially distal colon cancer.

PMID- 28516300
TI  - Predicting surgical skill from the first N seconds of a task: value over task
      time using the isogony principle.
AB  - PURPOSE: Most evaluations of surgical workflow or surgeon skill use simple,
      descriptive statistics (e.g., time) across whole procedures, thereby
      deemphasizing critical steps and potentially obscuring critical inefficiencies or
      skill deficiencies. In this work, we examine off-line, temporal clustering
      methods that chunk training procedures into clinically relevant surgical tasks or
      steps during robot-assisted surgery. METHODS: Features calculated from the
      isogony principle are used to train four common machine learning algorithms from
      dry-lab laparoscopic data gathered from three common training exercises. These
      models are used to predict the binary or ternary skill level of a surgeon. K-fold
      and leave-one-user-out cross-validation are used to assess the accuracy of the
      generated models. RESULTS: It is shown that the proposed scalar features can be
      trained to create 2-class and 3-class classification models that map to
      fundamentals of laparoscopic surgery skill level with median 85 and 63% accuracy
      in cross-validation, respectively, for the targeted dataset. Also, it is shown
      that the 2-class models can discern class at 90% of best-case mean accuracy with
      only 8 s of data from the start of the task. CONCLUSION: Novice and expert skill
      levels of unobserved trials can be discerned using a state vector machine trained
      with parameters based on the isogony principle. The accuracy of this
      classification comes within 90% of the classification accuracy from observing the
      full trial within 10 s of task initiation on average.

PMID- 28516303
TI  - Erratum to: Theoretical study of the H + HCN -> H + HNC process.

PMID- 28516302
TI  - The minimally acceptable classification criterion for surgical skill: intent
      vectors and separability of raw motion data.
AB  - PURPOSE: Minimally invasive surgery requires objective methods for skill
      evaluation and training. This work presents the minimally acceptable
      classification (MAC) criterion for computational surgery: Given an obvious novice
      and an obvious expert, a surgical skill evaluation classifier must yield 100%
      accuracy. We propose that a rigorous motion analysis algorithm must meet this
      minimal benchmark in order to justify its cost and use. METHODS: We use this
      benchmark to investigate two concepts: First, how separable is raw,
      multidimensional dry laboratory laparoscopic motion data between obvious novices
      and obvious experts? We utilized information theoretic techniques to analytically
      address this. Second, we examined the use of intent vectors to classify surgical
      skill using three FLS tasks. RESULTS: We found that raw motion data alone are not
      sufficient to classify skill level; however, the intent vector approach is
      successful in classifying surgical skill level for certain tasks according to the
      MAC criterion. For a pattern cutting task, this approach yields 100% accuracy in
      leave-one-user-out cross-validation. CONCLUSION: Compared to prior art, the
      intent vector approach provides a generalized method to assess laparoscopic
      surgical skill using basic motion segments and passes the MAC criterion for some
      but not all FLS tasks.

PMID- 28516301
TI  - Application fields for the new Object Management Group (OMG) Standards Case
      Management Model and Notation (CMMN) and Decision Management Notation (DMN) in
      the perioperative field.
AB  - PURPOSE: Medical processes can be modeled using different methods and notations.
      Currently used modeling systems like Business Process Model and Notation (BPMN)
      are not capable of describing the highly flexible and variable medical processes
      in sufficient detail. METHODS: We combined two modeling systems, Business Process
      Management (BPM) and Adaptive Case Management (ACM), to be able to model non
      deterministic medical processes. We used the new Standards Case Management Model
      and Notation (CMMN) and Decision Management Notation (DMN). RESULTS: First, we
      explain how CMMN, DMN and BPMN could be used to model non-deterministic medical
      processes. We applied this methodology to model 79 cataract operations provided
      by University Hospital Leipzig, Germany, and four cataract operations provided by
      University Eye Hospital Tuebingen, Germany. Our model consists of 85 tasks and
      about 20 decisions in BPMN. We were able to expand the system with more complex
      situations that might appear during an intervention. CONCLUSION: An effective
      modeling of the cataract intervention is possible using the combination of BPM
      and ACM. The combination gives the possibility to depict complex processes with
      complex decisions. This combination allows a significant advantage for modeling
      perioperative processes.

PMID- 28516304
TI  - Strategy for designing stable and powerful nitrogen-rich high-energy materials by
      introducing boron atoms.
AB  - One of the most important aims in the development of high-energy materials is to
      improve their stability and thus ensure that they are safe to manufacture and
      transport. In this work, we theoretically investigated open-chain N4B2 isomers
      using density functional theory in order to find the best way of stabilizing
      nitrogen-rich molecules. The results show that the boron atoms in these isomers
      are aligned linearly with their neighboring atoms, which facilitates close
      packing in the crystals of these materials. Upon comparing the energies of nine
      N4B2 isomers, we found that the structure with alternating N and B atoms had the
      lowest energy. Structures with more than one nitrogen atom between two boron
      atoms had higher energies. The energy of N4B2 increases by about 50 kcal/mol each
      time it is rearranged to include an extra nitrogen atom between the two boron
      atoms. More importantly, our results also show that boron atoms stabilize
      nitrogen-rich molecules more efficiently than carbon atoms do. Also, the
      combustion of any isomer of N4B2 releases more heat than the corresponding isomer
      of N4C2 does under well-oxygenated conditions. Our study suggests that the three
      most stable N4B2 isomers (BN13, BN24, and BN34) are good candidates for high
      energy molecules, and it outlines a new strategy for designing stable boron
      containing high-energy materials. Graphical abstract The structural
      characteristics, thermodynamic stabilities, and exothermic properties of nitrogen
      rich N4B2 isomers were investigated by means of density functional theory.

PMID- 28516305
TI  - Arsenic toxicity and epimutagenecity: the new LINEage.
AB  - Global methylation pattern regulates the normal functioning of a cell. Research
      have shown arsenic alter these methylation landscapes within the genome leading
      to aberrant gene expression and inducts various pathophysiological outcomes. Long
      interspersed nuclear elements (LINE-1) normally remains inert due to heavy
      methylation of it's promoters, time and various environmental insults, they lose
      these methylation signatures and begin retro-transposition that has been
      associated with genomic instability and cancerous outcomes. Of the various high
      throughput technologies available to detect global methylation profile,
      development of LINE-1 methylation index shall provide a cost effect-screening
      tool to detect epimutagenic events in the wake of toxic exposure in a large
      number of individuals. In the present review, we tried to discuss the state of
      research and whether LINE-1 methylation can be considered as a potent epigenetic
      signature for arsenic toxicity.

PMID- 28516306
TI  - Peritoneal metastasis from pancreatic cancer treated with pressurized
      intraperitoneal aerosol chemotherapy (PIPAC).
AB  - Patients with peritoneal metastasis (PM) from pancreatic cancer have a short life
      expectancy. Systemic combination chemotherapy leads to a median overall survival
      of 7-8 months. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a
      treatment alternative, where studies in patients with PM from ovarian, gastric
      and colorectal cancer show a high safety profile and interesting results. This
      case study report data on the PIPAC treatment in patients with PM from pancreatic
      cancer. In a standard laparoscopy, chemotherapeutics (cisplatin and doxorubicin)
      are nebulized within the peritoneal cavity. After 30 min, the chemotherapeutics
      are evacuated through a closed system. The PIPAC procedure is repeated every 4-6
      weeks. Five patients with PM from pancreatic cancer were treated with a total of
      16 PIPAC procedures. All patients received >1 PIPAC and were eligible for
      evaluation of histological regression. Four patients demonstrated histological
      regression, and one patient had stable disease. Three patients are still alive,
      and the median overall survival is 14 months (range 10-20) since the diagnosis of
      PM. The histological regression and survival figures in this pilot study suggest
      activity of PIPAC with low-dose cisplatin and doxorubicin in pretreated
      peritoneal metastasis of pancreatic origin. This should now be evaluated in
      prospective studies.

PMID- 28516307
TI  - Appropriate control time constant in relation to characteristics of the
      baroreflex vascular system in 1/R control of the total artificial heart.
AB  - 1/R control is a physiological control method of the total artificial heart (TAH)
      with which long-term survival was obtained with animal experiments. However, 1/R
      control occasionally diverged in the undulation pump TAH (UPTAH) animal
      experiment. To improve the control stability of the 1/R control, appropriate
      control time constant in relation to characteristics of the baroreflex vascular
      system was investigated with frequency analysis and numerical simulation. In the
      frequency analysis, data of five goats in which the UPTAH was implanted were
      analyzed with first Fourier transform technique to examine the vasomotion
      frequency. The numerical simulation was carried out repeatedly changing
      baroreflex parameters and control time constant using the elements-expanded
      Windkessel model. Results of the frequency analysis showed that the 1/R control
      tended to diverge when very low frequency band that was an indication of the
      vasomotion frequency was relative high. In numerical simulation, divergence of
      the 1/R control could be reproduced and the boundary curves between the
      divergence and convergence of the 1/R control varied depending on the control
      time constant. These results suggested that the 1/R control tended to be unstable
      when the TAH recipient had high reflex speed in the baroreflex vascular system.
      Therefore, the control time constant should be adjusted appropriately with the
      individual vasomotion frequency.

PMID- 28516308
TI  - The Charlie Sheen Effect on Rapid In-home Human Immunodeficiency Virus Test
      Sales.
AB  - One in eight of the 1.2 million Americans living with human immunodeficiency
      virus (HIV) are unaware of their positive status, and untested individuals are
      responsible for most new infections. As a result, testing is the most cost
      effective HIV prevention strategy and must be accelerated when opportunities are
      presented. Web searches for HIV spiked around actor Charlie Sheen's HIV-positive
      disclosure. However, it is unknown whether Sheen's disclosure impacted offline
      behaviors like HIV testing. The goal of this study was to determine if Sheen's
      HIV disclosure was a record-setting HIV prevention event and determine if Web
      searches presage increases in testing allowing for rapid detection and reaction
      in the future. Sales of OraQuick rapid in-home HIV test kits in the USA were
      monitored weekly from April 12, 2014, to April 16, 2016, alongside Web searches
      including the terms "test," "tests," or "testing" and "HIV" as accessed from
      Google Trends. Changes in OraQuick sales around Sheen's disclosure and prediction
      models using Web searches were assessed. OraQuick sales rose 95% (95% CI, 75-117;
      p < 0.001) of the week of Sheen's disclosure and remained elevated for 4 more
      weeks (p < 0.05). In total, there were 8225 more sales than expected around
      Sheen's disclosure, surpassing World AIDS Day by a factor of about 7. Moreover,
      Web searches mirrored OraQuick sales trends (r = 0.79), demonstrating their
      ability to presage increases in testing. The "Charlie Sheen effect" represents an
      important opportunity for a public health response, and in the future, Web
      searches can be used to detect and act on more opportunities to foster prevention
      behaviors.

PMID- 28516309
TI  - Assessing the Process of Retirement: a Cross-Cultural Review of Available
      Measures.
AB  - Retirement research is now expanding beyond the post-World War II baby boomers'
      retirement attitudes and plans to include the nature of their workforce exit and
      how successfully they adjust to their new life. These elements are collectively
      known as the process of retirement. However, there is insufficient research in
      developing countries to inform the management of their ageing populations
      regarding this process. This review aims to facilitate national and cross
      cultural research in developing and non-English speaking countries by reviewing
      the existing measures of the retirement process published in English and
      Portuguese. The review identified 28 existing measures assessing retirement
      attitudes, planning, decision making, adjustment and satisfaction with
      retirement. Information on each scale's item structure, internal reliability,
      grammatical structure and evidence of translations to other languages is
      presented. Of the 28 measures, 20 assessed retirement attitudes, plans and
      decision-making, 5 assessed adjustment to retirement and only two assessed
      retirement satisfaction. Only eight of the 28 scales had been translated into
      languages other than English. There is scope to translate measures of retirement
      attitudes and planning into other languages. However there is a paucity of
      translated measures of retirement decision-making and adjustment, and measures of
      retirement satisfaction in general. Within the limitations of this review,
      researchers are provided with the background to decide between translating
      existing measures or developing of more culturally appropriate assessment tools
      for addressing their research questions.

PMID- 28516310
TI  - Natural History of Patients Followed Radiographically with Mucinous Cysts of the
      Pancreas.
AB  - OBJECTIVE: The aim of this study was to evaluate the outcome of patients presumed
      to have mucinous cysts of the pancreas who were initially selected for
      radiographic surveillance. METHODS: Patients with a pancreatic cyst and a
      measured cyst fluid carcinoembryonic antigen (CEA) >=192 ng/mL were included.
      Patients were stratified by those who underwent initial resection and those who
      were recommended for radiographic surveillance. The natural history of these two
      groups was examined. RESULTS: From 1999 to 2014, 227 patients were identified who
      had a cyst fluid CEA >=192 ng/mL (median 961, range 192-300,000 ng/mL). Immediate
      resection was performed on 63 patients (28%). Initial radiographic surveillance
      was recommended for 164 patients; 87% did not have main pancreatic duct dilation,
      and 87% met consensus criteria for radiographic surveillance. After a median
      follow-up of 56 months, 48 of the 164 patients (29%) had undergone resection.
      Ultimately, there were three cases (2%) of high-grade dysplasia and two cases of
      invasive carcinoma (1%) within these 164 patients selected for observation. Three
      of the five cases of either high-grade dysplasia or invasive carcinoma were among
      the 22 patients followed outside of consensus guidelines. CONCLUSIONS:
      Appropriately selected patients with mucinous pancreatic cysts can be safely
      followed with serial surveillance with a low risk of malignant progression.

PMID- 28516311
TI  - Duodenal and Ampullary Carcinoid Tumors: Size Predicts Necessity for
      Lymphadenectomy.
AB  - BACKGROUND: Unlike other neuroendocrine tumors of the gastrointestinal tract,
      management of duodenal and periampullary carcinoids remains controversial. We
      aimed to determine the metastatic potential and optimal choice of therapy for
      these neoplasms. METHODS: A retrospective review of all patients treated at the
      Johns Hopkins Hospital between 1996 and 2012 was conducted. Clinicopathologic
      factors associated with lymph nodal involvement and clinical outcomes were
      evaluated. RESULTS: A total of 101 patients were identified. Eighty (79.2%)
      tumors arose from the duodenum and 21 (20.8%) from the periampullary area. Thirty
      five (34.7%) patients underwent pancreaticoduodenectomy (PD), 12 (11.9%) local
      resection, 38 (37.6%) endoscopic excision, and 16 (15.8%) patients harbored
      incidental tumors identified in the specimen after PD for another indication.
      Lymph node (LN) pathologic evaluation was done in 56 patients, among which 27
      (48%) had positive LN. Specifically, LN positivity (LN+) for tumors <1 cm in size
      was 4.5% (1/22), for tumors 1-2 cm 72% (13/18), and for tumors >2 cm 81% (13/16).
      Tumor size was the only factor associated with LN+ (p = 0.029). CONCLUSION: Lymph
      nodal involvement is common for duodenal and periampullary carcinoid tumors,
      particularly among those >1 cm in size; therefore, resection with
      lymphadenectomyfor these larger tumors is recommended.

PMID- 28516312
TI  - Macroinvertebrate Taxonomic and Functional Trait Compositions within Lotic
      Habitats Affected By River Restoration Practices.
AB  - The widespread degradation of lotic ecosystems has prompted extensive river
      restoration efforts globally, but many studies have reported modest ecological
      responses to rehabilitation practices. The functional properties of biotic
      communities are rarely examined within post-project appraisals, which would
      provide more ecological information underpinning ecosystem responses to
      restoration practices and potentially pinpoint project limitations. This study
      examines macroinvertebrate community responses to three projects which aimed to
      physically restore channel morphologies. Taxonomic and functional trait
      compositions supported by widely occurring lotic habitats (biotopes) were
      examined across paired restored and non-restored (control) reaches. The
      multivariate location (average community composition) of taxonomic and functional
      trait compositions differed marginally between control and restored reaches.
      However, changes in the amount of multivariate dispersion were more robust and
      indicated greater ecological heterogeneity within restored reaches, particularly
      when considering functional trait compositions. Organic biotopes (macrophyte
      stands and macroalgae) occurred widely across all study sites and supported a
      high alpha (within-habitat) taxonomic diversity compared to mineralogical
      biotopes (sand and gravel patches), which were characteristic of restored
      reaches. However, mineralogical biotopes possessed a higher beta (between
      habitat) functional diversity, although this was less pronounced for taxonomic
      compositions. This study demonstrates that examining the functional and
      structural properties of taxa across distinct biotopes can provide a greater
      understanding of biotic responses to river restoration works. Such information
      could be used to better understand the ecological implications of rehabilitation
      practices and guide more effective management strategies.

PMID- 28516314
TI  - Harmonic subtraction for evaluating right ventricle ejection fraction from planar
      equilibrium radionuclide angiography.
AB  - We report an initial investigation of a subtraction-based method to estimate
      right ventricle ejection fraction (RVEF) from ECG-gated planar equilibrium
      radionuclide angiography (ERNA) data. Twenty-six consecutive patients referred
      for scintigraphic evaluation of cardiac function prior to chemotherapy had ECG
      gated first-pass (FP) imaging and ERNA imaging performed following the same
      radiotracer injection. RVEF was computed from FP images (RVEFFP) and separately
      from ERNA images (RVEFERNA). Standard methods for computing ejection fractions
      were used to obtain RVEFFP values. RVEFERNA values were obtained using harmonic
      subtraction of the left ventricular contribution from a biventricular region of
      interest contoured on the equilibrium images acquired in the shallow right
      anterior oblique projection. Clinically acquired chest CT data were used to
      derive information regarding the relative position of the left and right
      ventricle and about the presence of pulmonary artery enlargement. Computation of
      RVEFERNA was successful for each of the 26 patients. Computation of RVEFFP failed
      for four patients. For the 22 patients for which RVEF was computed using both
      methods, the average RVEFFP was 49% and the average RVEFERNA was 51%, with
      coefficients of variation of 11 and 7.5%, respectively. Low RVEFERNA values were
      associated with pulmonary artery dilation. Estimation of RVEFERNA, using a
      harmonic subtraction-based method of computation is clinically feasible and
      accurate in the patient population studied. The results support further
      investigation in patients with frank heart failure.

PMID- 28516313
TI  - Dynamic changes in aortic impedance after transcatheter aortic valve replacement
      and its impact on exploratory outcome.
AB  - Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in
      medically managed aortic stenosis (AS) patients. We aimed to investigate the
      association between Zva and left ventricular (LV) adaptation and to explore the
      predictive value of Zva for cardiac functional recovery and outcome after
      transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128
      patients with AS who underwent TAVR. Zva was calculated as: (systolic blood
      pressure + mean transaortic gradient)/stroke volume index). Echocardiographic
      assessment occurred at baseline, 1-month and 1-year after TAVR. The primary
      endpoints were to investigate associations between Zva and global longitudinal
      strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to
      compare all-cause mortality after TAVR between patients with pre-defined Zva (=5
      mmHg m2/ml), stroke volume index (=35 ml/m2), and GLS (=-15%) cutoffs. The mean
      GLS was reduced (-13.0 +/- 3.2%). The mean Zva was 5.2 +/- 1.6 mmHg*m2/ml with
      55% of values >=5.0 mmHg*m2/ml, considered to be abnormally high. Higher Zva
      correlated with worse GLS (r = -0.33, p < 0.001). After TAVR, Zva decreased
      significantly (5.1 +/- 1.6 vs. 4.5 +/- 1.6 mmHg*m2/ml, p = 0.001). A reduction of
      Zva at 1-month was associated with GLS improvement at 1-month (r = -0.31, p =
      0.001) and at 1-year (r = -0.36 and p = 0.001). By Kaplan-Meier analysis,
      patients with higher Zva at baseline had higher mortality (Log-rank p = 0.046),
      while stroke volume index and GLS did not differentiate outcome (Log-rank p =
      0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS
      as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have
      an additional impact to traditional parameters on predicting worse mortality
      after TAVR.

PMID- 28516316
TI  - Venous thromboembolism after nephrectomy: incidence, timing and associated risk
      factors from a national multi-institutional database.
AB  - PURPOSE: To evaluate the rate of venous thromboembolism (VTE) after nephrectomy
      with specific focus on event timing and location (before or after hospital
      discharge) in order to identify modifiable risk factors and establish benchmarks
      for preventive interventions. METHODS: Using the ACS-NSQIP database, we
      identified patients undergoing nephrectomy from 2006 to 2012. Patients were
      analyzed in two cohorts: collectively and by surgical approach [open vs.
      lap/robotic (MIS)]. Rates of deep vein thrombosis (DVT) and pulmonary embolus
      (PE) were assessed and time to each event was established in relation to
      discharge status. Logistic regression analysis was performed to assess
      association between preoperative risk factors, surgical variables, and VTE.
      RESULTS: In total, 13,208 patients met inclusion criteria. The overall rate of
      VTE was 1.2% (PE = 0.5% and DVT = 0.8, 0.1% DVT and PE). Using regression
      analysis, diabetes, dependent functional status, and longer operative time were
      associated with higher odds of DVT. For PE, dyspnea, disseminated cancer, and
      longer operative time were significant associations. The rate of VTE was higher
      in open surgery compared to MIS (2 vs. 0.8%, p < 0.001). Median times to DVT and
      PE were 8.5 and 6 days, respectively, with 53.3% of DVTs and 63.1% of PEs
      occurring prior to discharge. CONCLUSIONS: The overall rate of VTE after
      nephrectomy is low, occurs roughly one week after surgery, and is associated with
      longer hospital stays. Certain patient factors, open surgical approach, and
      longer operative times were associated with higher odds of post-operative VTE;
      these patients may benefit from more aggressive prophylaxis.

PMID- 28516315
TI  - "Finding the needle in a haystack": oncologic evaluation of patients treated for
      LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral
      resection of the prostate (TURP).
AB  - PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing
      surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen
      patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively
      analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy,
      resected prostate weight, and histopathological features. Univariate and
      multivariate logistic regression models were used to identify independent
      predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a
      significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume
      (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after
      surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a
      prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP,
      respectively, the choice of procedure had no influence on the detection of iPCa
      (p = 0.593). However, a higher rate of false-negative preoperative prostate
      biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007).
      In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI
      1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as
      independent predictors for the detection of iPCa. CONCLUSIONS: Despite
      differences in oncologic parameters, the choice of technique had no influence on
      the detection of iPCa. Increased patient age and higher PSA density were
      associated with iPCa. A higher rate of false-negative preoperative prostate
      biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS
      patients requires a more adapted approach to exclude malignancy, especially in
      those with larger prostates.

PMID- 28516317
TI  - CD95-CD95L interaction mediates the growth control of MHV68 immortalized B cells
      by cytotoxic T cells.

PMID- 28516319
TI  - Quantitative prediction of drug side effects based on drug-related features.
AB  - MOTIVATION: Unexpected side effects of drugs are great concern in the drug
      development, and the identification of side effects is an important task.
      Recently, machine learning methods are proposed to predict the presence or
      absence of interested side effects for drugs, but it is difficult to make the
      accurate prediction for all of them. METHODS: In this paper, we transform side
      effect profiles of drugs as their quantitative scores, by summing up their side
      effects with weights. The quantitative scores may measure the dangers of drugs,
      and thus help to compare the risk of different drugs. Here, we attempt to predict
      quantitative scores of drugs, namely the quantitative prediction. Specifically,
      we explore a variety of drug-related features and evaluate their discriminative
      powers for the quantitative prediction. Then, we consider several feature
      combination strategies (direct combination, average scoring ensemble combination)
      to integrate three informative features: chemical substructures, targets, and
      treatment indications. Finally, the average scoring ensemble model which produces
      the better performances is used as the final quantitative prediction model.
      RESULTS: Since weights for side effects are empirical values, we randomly
      generate different weights in the simulation experiments. The experimental
      results show that the quantitative method is robust to different weights, and
      produces satisfying results. Although other state-of-the-art methods cannot make
      the quantitative prediction directly, the prediction results can be transformed
      as the quantitative scores. By indirect comparison, the proposed method produces
      much better results than benchmark methods in the quantitative prediction. In
      conclusion, the proposed method is promising for the quantitative prediction of
      side effects, which may work cooperatively with existing state-of-the-art methods
      to reveal dangers of drugs.

PMID- 28516318
TI  - Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a
      Meta-Analysis Based on Imputed Placebo Effect.
AB  - PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke
      prevention in patients with atrial fibrillation (AF); therefore, there is not
      equipoise when comparing newer oral anticoagulants with placebo in this setting.
      METHODS: To explore the effect of apixaban on mortality in patients with AF, we
      performed a meta-analysis of apixaban versus placebo using a putative placebo
      analysis based on randomized controlled clinical trials that compared warfarin,
      aspirin, and no antithrombotic control. We used data from two prospective
      randomized controlled trials for our comparison of apixaban versus warfarin
      (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial
      Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid
      to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are
      Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches,
      we indirectly compared apixaban with an imputed placebo with respect to the risk
      of death in patients with AF. We used results from meta-analyses of randomized
      trials as our reference for the comparison between warfarin and placebo/no
      treatment, and aspirin and placebo/no treatment. RESULTS: In these meta-analyses,
      a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95%
      confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07)
      versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban
      reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6
      52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled
      reduction in all-cause death with apixaban compared with an imputed placebo was
      34% (95% CI 18-47%; p = 0.0002). CONCLUSIONS: In patients with AF, indirect
      comparisons suggest that apixaban reduces all-cause death by approximately one
      third compared with an imputed placebo.

PMID- 28516320
TI  - How does the presence of a conspecific individual change the behavioral game that
      a predator plays with its prey?
AB  - Behavioral games predators play among themselves may have profound effects on
      behavioral games predators play with their prey. We studied the behavioral game
      between predators and prey within the framework of social foraging among
      predators. We tested how conspecific interactions among predators (little egret)
      change the predator-prey behavioral game and foraging success. To do so, we
      examined foraging behavior of egrets alone and in pairs (male and female) in a
      specially designed aviary consisting of three equally spaced pools with identical
      initial prey (comet goldfish) densities. Each pool was comprised of a risky
      microhabitat, rich with food, and a safe microhabitat with no food, forcing the
      fish to trade off food and safety. When faced with two versus one egret, we found
      that fish significantly reduced activity in the risky habitat. Egrets in pairs
      suffered reduced foraging success (negative intraspecific density dependence) and
      responded to fish behavior and to their conspecific by changing their visiting
      regime at the different pools-having shorter, more frequent visits. The time
      egret spent on each visit allowed them to match their long-term capture success
      rate across the environment to their capture success rate in the pool, which
      satisfies one aspect of optimality. Overall, egrets in pairs allocated more time
      for foraging and changed their foraging tactics to focus more on fish under cover
      and fish 'peeping' out from their shelter. These results suggest that both prey
      and predator show behavioral flexibility and can adjust to changing conditions as
      needed in this foraging game.

PMID- 28516321
TI  - Evaluating local adaptation of a complex phenotype: reciprocal tests of pigmy
      rattlesnake venoms on treefrog prey.
AB  - Theory predicts that predator-prey interactions can generate reciprocal selection
      pressures on species pairs, which can result in local adaptation, yet the
      presence and pattern of local adaptation is poorly studied in vertebrate predator
      prey systems. Here, we used a reciprocal common garden (laboratory) experimental
      design involving comparisons between local and foreign populations to determine
      if local adaptation was present between a generalist predator-the pigmy
      rattlesnake (Sistrurus miliarius)-and a co-occurring prey-the squirrel treefrog
      (Hyla squirella). We conducted toxicity trials using snake venom from two
      populations separated by 340 km tested on prey from sympatric and allopatric
      populations, resulting in data from four venom origin-frog origin combinations.
      We assessed venom effectiveness using two measures (frog mortality at 24 h and
      time to frog death) and then used regression analyses to look for a signal of
      local adaptation with either measure. We found evidence for local adaptation for
      one measure (time to death), but not the other (frog mortality). We argue that in
      this system, the time to death of a prey item is a more ecologically relevant
      measure of venom effectiveness than is frog mortality at 24 h. Our results
      document an example of local adaptation between two interacting vertebrates using
      a whole-organism assay and a local versus foreign criteria and provide evidence
      that population-level variation in snake venom is adaptive.

PMID- 28516323
TI  - Diffusion tensor imaging findings of the brainstem in subjects with tonsillar
      ectopia.
AB  - We aimed to evaluate the differences between apparent diffusion coefficient
      (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity
      (RD) values obtained from different cranial sites in subjects with Chiari I
      Malformation (CM-I) and borderline tonsillar ectopia (BTE), and to determine
      correlations between diffusion tensor imaging (DTI) metrics and the severity of
      tonsillar ectopia. A total of 73 subjects with CM-I and BTE and 35 control
      underwent MRI and DTI. In our study, ADC values measured from the level of
      medulla oblongata and the RD values measured in middle cerebellar peduncles,
      thalamus, and globus pallidus were higher in CM-I patients than in controls. FA
      values at the medulla oblongata level and AD values at the medulla oblongata and
      pons level higher in patients with CM-I. ADC and AD values measured at the pons
      level were higher in BTE subjects than in controls. Compared with BTE, the CM-I
      subjects' ADC values at the medulla oblongata and AD values at the pons level
      were higher. In addition, FAs at the pons and medulla oblongata level were
      higher. At the medulla oblongata level, a positive correlation was observed
      between ADC and the size of tonsillar ectopia. AD and FA values measured at the
      level of medulla oblongata and pons were positively correlated with the size of
      tonsillar ectopia. These findings may be related to the severity of
      microstructural changes involving neuronal tracts at the brainstem level due to
      tonsillar ectopia. DTI may be useful in determining the extent of microstructural
      changes at the tissue level in subjects with tonsillar ectopia.

PMID- 28516322
TI  - Do functional diversity and trait dominance determine carbon storage in an
      altered tropical landscape?
AB  - Altered landscapes play a major role in biodiversity conservation and carbon (C)
      storage in the tropics. There is increasing evidence that C storage potential is
      controlled by tree functional diversity, but underlying mechanisms are debated.
      We analyzed the effects of trait dominance (mass-ratio hypothesis), species
      diversity, and trait variation (species complementarity) on C storage in the
      soils and vegetation of 20 agroforestry systems (AFS) and seven forested sites in
      Costa Rica. AFS consisted of organic and conventional coffee farms and pastures
      with trees. We used the community weighted mean (CWM) to measure trait dominance,
      and functional divergence (FDvar) to evaluate trait variation of wood densities
      (WD) and maximum heights (H max) of woody plants at each site. Species richness,
      the number of woody plants per hectare, and slope of the terrain were also
      considered as independent variables. Soil organic carbon (SOC) increased with
      higher CWMWD and with higher variability of H max ([Formula: see text]) across
      land-use types. Aboveground carbon (AGC) was controlled by the number of woody
      plants per hectare and by species richness. Our results suggest that dominant
      traits as well as species complementarity play an important role in determining C
      storage. Diverse, multilayered AFS which incorporate trees with high WD, combined
      with the conservation of remnant forests, can maximize C storage in the soils and
      vegetation of altered tropical landscapes.

PMID- 28516326
TI  - Capsule Commentary on Steinman et al., Epidemic Use of Benzodiazepines among
      Older Adults in Israel: Epidemiology and Leverage Points for Improvement.

PMID- 28516325
TI  - Capsule Commentary on Bennett et al., Engaging Stakeholders to Inform Clinical
      Practice Guidelines that Address Multiple Chronic Conditions.

PMID- 28516324
TI  - Bacterial intelligence: imitation games, time-sharing, and long-range quantum
      coherence.
AB  - Bacteria are far more intelligent than we can think of. They adopt different
      survival strategies to make their life comfortable. Researches on bacterial
      communication to date suggest that bacteria can communicate with each other using
      chemical signaling molecules as well as using ion channel mediated electrical
      signaling. Though in past few decades the scopes of chemical signaling have been
      investigated extensively, those of electrical signaling have received less
      attention. In this article, we present a novel perspective on time-sharing
      behavior, which maintains the biofilm growth under reduced nutrient supply
      between two distant biofilms through electrical signaling based on the
      experimental evidence reported by Liu et al., in 2017. In addition, following the
      recent work by Humphries et al. Cell 168(1):200-209, in 2017, we highlight the
      consequences of long range electrical signaling within biofilm communities
      through spatially propagating waves of potassium. Furthermore, we address the
      possibility of two-way cellular communication between artificial and natural
      cells through chemical signaling being inspired by recent experimental
      observation (Lentini et al. 2017) where the efficiency of artificial cells in
      imitating the natural cells is estimated through cellular Turing test. These
      three spectacular observations lead us to envisage and devise new classical and
      quantum views of these complex biochemical networks that have never been realized
      previously.

PMID- 28516328
TI  - Chronic traumatic encephalopathy: identifying those at risk and understanding
      pathogenesis.

PMID- 28516327
TI  - Long-term outcomes of epilepsy surgery in tuberous sclerosis complex.
AB  - Approximately 50% of patients with tuberous sclerosis complex (TSC) present
      intractable epilepsy, and surgery is an option for those patients. Hereby, we
      analyze long-term seizure control and neuropsychological outcomes of epilepsy
      surgery in patients with TSC. Clinical data were retrospectively collected from
      66 patients with TSC and epilepsy followed up over 5 years, 51 of whom underwent
      epilepsy surgery between 2001 and 2011. Reductions in the number of seizures were
      analyzed at 1-year (1FU), 5-year (5FU), and 10-year (10FU) follow-ups visits
      after the operation. Influential factors on postoperative seizure free and
      intelligence quotient (IQ) and quality-of-life (QOL) outcomes were evaluated at
      5FU. Resective procedures included 26 tuber resections, 15 lobectomies, and 10
      tuber resections and lobectomies. Corpus callosotomies were performed as the
      adjunctive approach in 11 cases with low IQ. The percentages of seizure-free
      cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive
      factor for long-term postoperative seizure freedom was the history of
      preoperative seizures and preoperative full-scale IQ. Significant improvements
      were found in performance IQ, full-scale IQ, and QOL in patients from the surgery
      group, particularly those who were seizure free after the operation. Our study
      showed that epilepsy surgery in TSC with epilepsy rendered improvements in
      seizure control, full-scale IQ, and QOL. Satisfactory long-term seizure control
      was often achieved with an early operation and without mental retardation, and
      improvements in QOL and IQ were frequently observed in postoperative patients who
      remained seizure free.

PMID- 28516330
TI  - Why antisense could make sense for neurodegeneration.

PMID- 28516329
TI  - Screening for lipoprotein receptor-related protein 4-, agrin-, and titin
      antibodies and exploring the autoimmune spectrum in myasthenia gravis.
AB  - In autoimmune myasthenia gravis (MG), the identification of antibodies and
      characterization of serological subgroups is of great importance for diagnosis
      and management of the disease. Our aims were to study the frequency of antibodies
      against lipoprotein-related protein 4 (LRP4), agrin, and titin using the most
      recent techniques, and to characterize corresponding clinical features and
      autoimmune diseases (AID) in 100 MG-patients. The antibody frequencies in the 55
      AChR-antibody positive patients were 7% LRP4, 5% agrin, 53% titin, and in the 45
      AChR-antibody negative patients 2% MuSK, 2% LRP4, 2% agrin, and 27% titin. LRP4
      MG presented late-onset age, mild symptoms, good therapeutic response, and no
      thymic changes. Agrin-MG showed early onset age, mild-to-severe symptoms, and
      moderate treatment response. The phenotype of titin-MG depended on AChR
      antibodies: AChR-antibody negative patients presented with mostly mild limb
      muscle weakness, whereas AChR-antibody positive patients showed more frequently
      severe symptoms, including myasthenic crisis, bulbar predominance, and thymoma.
      Additional AID were detected in 32% of MG-patients, most frequently Hashimoto's
      thyroiditis (21%). Based on our data, we recommend the detection of LRP4
      antibodies for at least AChR-antibody negative MG-patients and titin-antibodies
      for all MG-patients. We propose taking an accurate medical history for typical
      symptoms of Hashimoto's thyroiditis in MG-patients.

PMID- 28516332
TI  - Prevalence and mortality of patients with multiple sclerosis in France in 2012: a
      study based on French health insurance data.
AB  - Data on the prevalence of multiple sclerosis (MS) in France are scarce. National
      and regional updated estimates are needed to better plan health policies. In this
      nationwide study, we provided estimates of the prevalence of MS in France in 2012
      and mortality rate in 2013. MS cases were identified in the French national
      health insurance database (SNIIRAM-PMSI) using reimbursement data for disease
      modifying treatment, long-term disease status for MS, disability pension for MS,
      and hospitalisation for MS (MS ICD-10 code: G35). We identified 99,123 MS cases,
      corresponding to an overall crude prevalence rate of 151.2 per 100,000
      inhabitants [95% confidence interval (CI) 150.3-152.2]: 210.0 per 100,000 in
      women (95% CI 208.4-211.5) and 88.7 per 100,000 in men (95% CI 87.6-89.7). The
      overall prevalence rate was 155.6 per 100,000 inhabitants (95% CI 154.7-156.6)
      after standardization on the 2013-European population. We observed a prevalence
      gradient with a higher prevalence (190-200 per 100,000) in North-Eastern France
      and a lower prevalence in Southern and Western France (126-140). The crude
      mortality rate in 2013 was 13.7 per 1,000 MS cases (11.4 in women and 20.3 in
      men). The standardized mortality ratio was 2.56 (95% CI 2.41-2.72). Our results
      revise upwards the estimation of MS prevalence in France and confirm the excess
      mortality of MS patients compared to the general population.

PMID- 28516331
TI  - Burden of herpes simplex virus encephalitis in the United States.
AB  - Herpes simplex virus encephalitis (HSVE) is a disease of public health concern,
      but its burden on the healthcare of United States has not been adequately
      assessed recently. We aimed to define the incidence, complications and outcomes
      of HSVE in the recent decade by analyzing data from a nationally representative
      database. Healthcare Cost and Utilization Project databases were utilized to
      identify patients with primary discharge diagnosis of HSVE. Annual
      hospitalization rate was estimated and several preselected inpatient
      complications were identified. Regression analyses were used to identify
      mortality predictors. Key epidemiological factors were compared with those from
      other countries. Total 4871 patients of HSVE were included in our study. The
      annual hospitalization rate was 10.3 +/- 2.2 cases/million in neonates, 2.4 +/-
      0.3 cases/million in children and 6.4 +/- 0.4 cases/million in adults. Median age
      was 57 years and male:female incidence ratio was 1:1. Rates of some central
      nervous system complications were seizures (38.4%), status epilepticus (5.5%),
      acute respiratory failure (20.1%), ischemic stroke (5.6%) and intracranial
      hemorrhage (2.7%), all of which were significantly associated with mortality. In
      hospital mortality in neonates, children and adults were 6.9, 1.2 and 7.7%,
      respectively. HSVE still remains a potentially lethal infectious disease with
      high morbidity and mortality. Most recent epidemiological data in this study may
      help understanding this public health disease, and the patient outcome data may
      have prognostic significance.

PMID- 28516333
TI  - Risk of Hip Fracture in Older People Using Selective Serotonin Reuptake
      Inhibitors and Other Psychoactive Medicines Concurrently: A Matched Case-Control
      Study in Australia.
AB  - BACKGROUND: Few studies have assessed the risk of hip fracture following
      concurrent use of psychoactive medicines, and none has investigated combinations
      with selective serotonin reuptake inhibitors. OBJECTIVES: To assess the risk of
      hip fracture in older people as a result of concurrent use of selective serotonin
      reuptake inhibitors and other psychoactive medicines. METHODS: A matched case
      control design was employed. Cases were Australian Government Department of
      Veterans' Affairs beneficiaries aged over 65 years who experienced a hip fracture
      between 2009 and 2012. Each case was matched with up to four randomly selected
      controls of the same age (+/-2 years) and sex. Medicine-hip fracture associations
      were estimated via conditional logistic regression. The relative excess risk due
      to interaction (RERI) was calculated to determine whether combined effects
      differed from the sum of individual effects. RESULTS: There were 8828 cases and
      35,310 controls. The median age of subjects was 88 years and 63% were women. The
      risk of hip fracture was elevated for all medicines assessed individually, most
      notably selective serotonin reuptake inhibitors (initiation: odds ratio [OR] =
      2.7, 95% confidence interval [CI] 2.1, 3.6) and opioids (initiation: OR = 2.3,
      95% CI 1.9, 2.9). Combinations associated with an increased odds of hip fracture
      included addition of benzodiazepines to selective serotonin reuptake inhibitor
      therapy (OR = 3.0, 95% CI 1.9, 4.8; RERI = 0.9, 95% CI -0.5, 2.3), concurrent use
      of both opioids and selective serotonin reuptake inhibitors (OR = 2.2, 95% CI
      1.9, 2.6; RERI = 0.1, 95% CI -0.3, 0.5), addition of opioids to selective
      serotonin reuptake inhibitor therapy (OR = 3.2, 95% CI 1.8, 5.5; RERI = -0.1, 95%
      CI -2.0, 1.7), and initiation of both benzodiazepines and selective serotonin
      reuptake inhibitors (OR = 4.7, 95% CI 1.7, 13; RERI = 1.3, 95% CI -3.8, 6.3). The
      RERI results suggested that the effect of each of these medicine combinations
      equalled the sum of the effects of individual medicine use. CONCLUSIONS: In older
      people, the concurrent use of selective serotonin reuptake inhibitors and other
      psychoactive medicines increased the risk of hip fracture as much as the sum of
      the risks owing to individual medicine use. Our results highlight the need for
      prescribers to consider the sedative burden of medicines in each older patient as
      well as the potential for an additive risk of hip fracture when initiating
      additional psychoactive therapy.

PMID- 28516334
TI  - In the Real-World, Kids Use Medications and Devices.
AB  - In the real world, we lack evidence guiding the use of medications and devices in
      children. This lack of evidence arose out of the challenges of conducting
      clinical trials in children and other vulnerable populations and the historical
      decision (reversed in recent decades) to exclude children from clinical trials.
      The recent focus on the potential of real-world evidence (RWE) to guide approval
      and use of new treatments may provide a much-needed solution. A broad definition
      of RWE includes prospective observational data and data from electronic health
      records and claims, as well as other sources. For the most part, it is reasonable
      to expect that considerations around the use of RWE in adult populations will
      apply to its use in children. However, a number of issues around the use of RWE
      are unique to studying children. These fall into at least four categories: (1)
      identification of databases with adequate numbers of children in the age sub
      groups of interest, (2) access to critical variables such as birth date, birth
      weight, and gestational age, (3) linkage to parental records for information
      about pre-natal exposures, family history, and socio-economic status, and (4)
      linkage to school records for information about outcomes such as missed school
      days, academic progress, and behavioral issues. Addressing the needs of children
      in developing methodologies for use of RWE ensures that ongoing efforts will
      benefit children as well as other sectors of the population.

PMID- 28516337
TI  - Mesoscopic organization in ionic liquids.
AB  - We discuss some published results and provide new observations concerning the
      high level of structural complexity that lies behind the nanoscale correlations
      in ionic liquids (ILs) and their mixtures with molecular liquids. It turns out
      that this organization is a consequence of the hierarchical construction on both
      spatial (from angstrom to several nanometer) and temporal (from fraction of
      picosecond to hundreds of nanosecond) scales, which requires joint use of
      experimental and computational tools.

PMID- 28516335
TI  - Prognostic value of pre-treatment 18F-FDG-PET uptake in small-cell lung cancer.
AB  - PURPOSE: Small-cell lung cancer (SCLC) is an aggressive disease, despite an
      initially favorable response to treatment, and its prognosis is still poor.
      Multiple parameters have been studied as possible prognostic factors, but none of
      them are reliable enough to change the treatment approach. 18F-fluorodeoxyglucose
      positron emission tomography (FDG-PET) is a novel imaging technique for staging
      of SCLC. The aim of this study was to evaluate the prognostic value of pre
      treatment FDG-PET parameters on clinical outcome in limited stage (LS) SCLC
      patients treated with curative thoracic radiotherapy (RT) and chemotherapy.
      METHODS: Clinical records of 46 LS-SCLC patients with pre-treatment FDG-PET
      imaging were retrospectively reviewed. Patients were treated with definitive RT
      for a total dose of 50-60 Gy and chemotherapy. The clinical endpoints were
      progression-free survival (PFS) and overall survival (OS). RESULTS: The median
      age was 59 (range 30-82) years, and median follow-up time was 23.2 months (range
      5-82.8 months). Median OS was 30.9 months for pre-treatment tumor maximum
      standardized uptake value (SUVmax) <9.3 and 20.6 months for SUVmax >=9.3 (p =
      0.027) and PFS was 55.6 months for SUVmax <9.3 and 38.6 months for SUVmax >=9.3
      (p = 0.16). Median OS was 73 months for pre-treatment lymph node SUVmax <5.8 and
      21 months for >=5.8 (p = 0.01) and PFS was 38.6 months (range 6.8-70.3 months)
      for SUVmax-LN >=5.8; all patients with SUVmax-LN <5.8 were alive (p = 0.07).
      Median survival time was 28.2 months (range 21.7-34.7 months) for patients
      younger than 65 and 8.7 months (range 5.7-11.8 months) for those >=65 years (p =
      0.00). CONCLUSIONS: Pre-treatment FDG-PET uptake may be a valuable tool to
      evaluate prognosis in SCLC patients. Patients with a higher pre-treatment FDG
      uptake may be considered at increased risk of failure and may benefit from more
      aggressive treatment approaches.

PMID- 28516336
TI  - Changes of functional connectivity of the anterior cingulate cortex in women with
      primary dysmenorrhea.
AB  - Primary dysmenorrhea (PDM), a common gynecological disorder, is associated with
      structural and functional alterations in several subregions of the anterior
      cingulate cortex (ACC). However, systematic functional connectivity of the ACC
      subregions in PDM has not been clarified. In this study, we used resting-state
      functional magnetic resonance imaging (fMRI) data from forty-eight PDM patients
      and thirty-eight matched female healthy controls to investigate the functional
      connectivity of ACC subregions in PDM. Compared to healthy controls, PDM patients
      exhibited increased connectivity between the caudal ACC (cACC) and primary
      somatosensory cortex (SI), between the perigenual ACC (pACC) and caudate, and
      between the subgenual ACC (sACC) and medial prefrontal cortex (mPFC). PDM
      patients also showed decreased connectivity between the pACC and precuneus. In
      PDM group, the connectivity of the right pACC-right caudate positively correlated
      with disease duration, and the connectivity of the left pACC-left precuneus
      negatively correlated with disease severity. These present findings reveal that
      abnormal ACC connectivity may be implicated in the PDM-related disturbances in
      pain sensory, modulation, and affection. We hope that our study could enhance the
      understanding of the pathophysiology underlying PDM.

PMID- 28516339
TI  - Holding Manufacturers of Defective Firearms to Account: Does Restricting
      Liability Lawsuits Violate the Second Amendment?
AB  - Judicial and statutory developments since 2005 have placed considerable
      roadblocks in the way of legal efforts against the epidemic of gun violence in
      the United States. Although the Second Amendment is most often cited by those
      opposed to gun control, it offers a potential opportunity to be invoked in
      support of harm minimization.

PMID- 28516338
TI  - Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu
      Temple (Bali, Indonesia).
AB  - Robbing and bartering (RB) is a behavioral practice anecdotally reported in free
      ranging commensal macaques. It usually occurs in two steps: after taking inedible
      objects (e.g., glasses) from humans, the macaques appear to use them as tokens,
      returning them to humans in exchange for food. While extensively studied in
      captivity, our research is the first to investigate the object/food exchange
      between humans and primates in a natural setting. During a 4-month study in 2010,
      we used both focal and event sampling to record 201 RB events in a population of
      long-tailed macaques (Macaca fascicularis), including four neighboring groups
      ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we
      documented the RB frequency, prevalence and outcome, and tested the underpinning
      anthropogenic and demographic determinants. In line with the environmental
      opportunity hypothesis, we found a positive qualitative relation at the group
      level between time spent in tourist zones and RB frequency or prevalence. For two
      of the four groups, RB events were significantly more frequent when humans were
      more present in the environment. We also found qualitative partial support for
      the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in
      groups with higher ratios of (sub)adult males], whereas the group density
      hypothesis was not supported. This preliminary study showed that RB is a
      spontaneous, customary (in some groups), and enduring population-specific
      practice characterized by intergroup variation in Balinese macaques. As such, RB
      is a candidate for a new behavioral tradition in this species.

PMID- 28516340
TI  - Social studying and learning among medical students: a scoping review.
AB  - INTRODUCTION: Medical students study in social groups, which influence their
      learning, but few studies have investigated the characteristics of study groups
      and the impacts they have on students' learning. A scoping review was conducted
      on the topic of informal social studying and learning within medical education
      with the aim of appraising what is known regarding medical student attitudes to
      group study, the impact of group study on participants, and the methods that have
      been employed to study this. METHODS: Using Arksey and O'Malley's scoping review
      principles, MEDLINE, EMBASE and CINAHL were searched, along with hand-searching
      and a targeted search of the grey literature; 18 peer reviewed and 17 grey
      literature records were included. RESULTS: Thematic conceptual analysis
      identified a number of themes, including: the nature of group study; the utility
      and value of group studying including social learning facilitating student
      engagement, social learning as a source of motivation and accountability, and
      social learning as a source of wellbeing; and student preferences related to
      group studying, including its homophilic nature, transgressiveness, and
      effectiveness. Despite these emerging factors, the evidence base for this
      phenomenon is small. DISCUSSION: The findings in this scoping review demonstrate
      a clear role for social interaction outside of the classroom, and encourage us to
      consider the factors in student networking, and the implications of this on
      medical students' academics. We also highlight areas in need of future research
      to allow us to better situate informal social learning within medical education
      and to enable educators to support this phenomenon.

PMID- 28516341
TI  - Fairness: the hidden challenge for competency-based postgraduate medical
      education programs.
AB  - Competency-based medical education systems allow institutions to individualize
      teaching practices to meet the needs of diverse learners. Yet, the focus on
      continuous improvement and individualization of curricula does not exempt
      programs from treating learners in a fair manner. When learners fail to meet key
      competencies and are placed on probation or dismissed from training programs,
      issues of fairness may form the basis of their legal claims. In a literature
      search, we found no in-depth examination of fairness. In this paper, we utilize a
      systems lens to examine fairness within postgraduate medical education contexts,
      focusing on educational opportunities, assessment practices, decision-making
      processes, fairness from a legal standpoint, and fairness in the context of the
      learning environment. While we provide examples of fairness issues within US
      training programs, concerns regarding fairness are relevant in any medical
      education system which utilizes a competency-based education framework.Assessment
      oversight committees and annual programmatic evaluations, while recommended, will
      not guarantee fairness within postgraduate medical education programs, but they
      can provide a window into 'hidden' threats to fairness, as everything from
      training experiences to assessment practices may be examined by these committees.
      One of the first steps programs can take is to recognize that threats to fairness
      may exist in any educational program, including their own, and begin
      conversations about how to address these issues.

PMID- 28516342
TI  - Pharmacokinetic Bioequivalence Studies of an Extended-Release Oxycodone
      Hydrochloride Tablet in Healthy Japanese Subjects Under Fasting and Fed
      Conditions Without an Opioid Antagonist.
AB  - Oxycodone is a semisynthetic opioid used for the treatment of moderate to severe
      pain. Two separate studies were conducted to assess the pharmacokinetic
      bioequivalence of a newly formulated oxycodone hydrochloride extended-release
      tablet to a marketed oxycodone product in Japan under fasting and fed conditions.
      Each study was a randomized, open-label, single-dose, single-center, two-period,
      two-way crossover study. Healthy male Japanese subjects received the oxycodone 10
      mg products under fasting and fed conditions. Blood samples were collected at
      specified time intervals, and plasma concentrations of oxycodone were analyzed
      using a validated liquid chromatography tandem mass spectrometry assay method.
      The pharmacokinetic parameters were determined via non-compartmental analysis.
      Pharmacokinetic metrics used for bioequivalence assessment were the maximum
      observed plasma concentration (C max) and the area under the concentration-time
      curve up to the last sampling time (AUC t ). A total of 24 healthy subjects were
      enrolled in each study. One subject withdrew after completion of the first
      sequence under fed conditions. The ratios of geometric least square means for C
      max and AUC t under fasting conditions were 1.1110 (90% confidence interval [CI]
      1.0562-1.1687) and 0.9946 (90% CI 0.9670-1.0231), respectively. The ratios of
      geometric least square means for C max and AUCt under fed conditions were 1.1417
      (90% CI 1.0959-1.1895) and 1.0135 (90% CI 0.9810-1.0470), respectively. The 90%
      CIs were within the predefined range (0.80-1.25). Both treatments were well
      tolerated when taken without an opioid antagonist in healthy Japanese subjects.
      Pharmacokinetic bioequivalence between test and reference formulations under
      fasting and fed conditions was concluded in terms of both rate and extent of
      absorption.

PMID- 28516343
TI  - Therapeutic dormancy to delay postsurgical glioma recurrence: the past, present
      and promise of focal hypothermia.
AB  - Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for
      glioma. However, despite multimodal treatment, most glioma patients die from
      local recurrence in the resection margin. Glioma surgery is inherently lesional,
      and the response of brain tissue to surgery includes hemostasis, angiogenesis,
      reactive gliosis and inflammation. Unfortunately, these processes are also
      associated with tumorigenic side-effects. An increasing amount of evidence
      indicates that the response to a surgery-related brain injury is hijacked by
      residual glioma cells and participates in the local regeneration of tumor tissues
      at the resection margin. Inducing therapeutic hypothermia in the brain has long
      been used to treat the secondary damage, such as neuroinflammation and edema,
      that are caused by accidental traumatic brain injuries. There is compelling
      evidence to suggest that inducing therapeutic hypothermia at the resection margin
      would delay the local recurrence of glioma by (i) limiting cell proliferation,
      (ii) disrupting the pathological connection between inflammation and glioma
      recurrence, and (iii) limiting the consequences of the functional heterogeneity
      and complexity inherent to the tumor ecosystem. While the global whole-body
      cooling methods that are currently used to treat stroke in clinical practice may
      not adequately treat the resection margin, the future lies in implantable focal
      microcooling devices similar to those under development for the treatment of
      epilepsy. Preclinical and clinical strategies to evaluate focal hypothermia must
      be implemented to prevent glioma recurrence in the resection margin. Placing the
      resection margin in a state of hibernation may potentially provide such a long
      awaited therapeutic breakthrough.

PMID- 28516345
TI  - Performance and cost evaluation of health information systems using micro-costing
      and discrete-event simulation.
AB  - Innovation and health-care funding reforms have contributed to the deployment of
      Information and Communication Technology (ICT) to improve patient care. Many
      health-care organizations considered the application of ICT as a crucial key to
      enhance health-care management. The purpose of this paper is to provide a
      methodology to assess the organizational impact of high-level Health Information
      System (HIS) on patient pathway. We propose an integrated performance evaluation
      of HIS approach through the combination of formal modeling using the Architecture
      of Integrated Information Systems (ARIS) models, a micro-costing approach for
      cost evaluation, and a Discrete-Event Simulation (DES) approach. The methodology
      is applied to the consultation for cancer treatment process. Simulation scenarios
      are established to conclude about the impact of HIS on patient pathway. We
      demonstrated that although high level HIS lengthen the consultation, occupation
      rate of oncologists are lower and quality of service is higher (through the
      number of available information accessed during the consultation to formulate the
      diagnostic). The provided method allows also to determine the most cost-effective
      ICT elements to improve the care process quality while minimizing costs. The
      methodology is flexible enough to be applied to other health-care systems.

PMID- 28516344
TI  - Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for
      clinical setting in glioblastoma patients.
AB  - Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in
      the treatment of glioblastoma (GBM). Hypermethylation in O6-methylguanine-DNA
      methyltransferase (MGMT) promoter is thought to play a critical role in this
      resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for
      MGMT promoter methylation testing. The unresolved issue is the determination of a
      cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT
      methylated" and "MGMT unmethylated" patient subgroups as a basis for further
      treatment decisions. In this study, receiver operating characteristic (ROC) curve
      analysis was used to identify an optimal cutoff of MGMT promoter methylation by
      testing mean percentage of methylation of 4 CpG islands (76-79) within MGMT exon
      1. The area under the ROC (AUC) as well as the best cutoff to classify the
      methylation were calculated. Positive likelihood ratio (LR+) was chosen as a
      diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed
      whether mean percentage of methylation at the investigated CpG islands could be
      regarded as a marker for evaluating prognostication. ROC analysis showed that the
      optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response
      to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter
      methylation, which was confirmed using validation set. According to the cutoff
      value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation
      level of the investigated CpG sites strong correlated with overall survival (OS),
      which means GBM patients with a high level of methylation survived longer than
      those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC
      curve analysis enables the best cutoff for discriminating MGMT promoter
      methylation status. LR+ can be used as a key factor that evaluates cutoff. The
      promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.

PMID- 28516346
TI  - Site, Sector, Scope: Mapping the Epistemological Landscape of Health Humanities.
AB  - This essay presents a critical appraisal of the current state of baccalaureate
      Health Humanities, with a special focus on the contextual differences currently
      influencing the implementation of this field in Canada and, to a lesser extent,
      the United States and United Kingdom. I argue that the epistemological bedrock of
      Health Humanities goes beyond that generated by its written texts to include
      three external factors that are especially pertinent to undergraduate education:
      site (the setting of Health Humanities education), sector (the disciplinary
      eligibility for funding) and scope (the critical engagement with a program's
      local context alongside an emergent "core" of Health Humanities knowledge,
      learning, and practice). Drawing largely from the Canadian context, I discuss how
      these differences can inform or obstruct this field's development, and offer
      preliminary recommendations for encouraging the growth of baccalaureate Health
      Humanities-in Canada and elsewhere-in light of these factors.

PMID- 28516347
TI  - Uniting the Pre-Health Humanities with the Introductory Composition Course.
AB  - Drawing on my experiences at a teaching-focused university, I show how locating
      the health humanities in first-year or introductory composition courses improves
      learning and offers an economical, flexible, and far-reaching approach to
      bringing a health humanities education to all baccalaureate-level learners,
      regardless of whether they aspire to careers in the health professions. In terms
      of improving learning, health humanities composition courses support the
      disciplinary aims of both fields. Accessible, relevant issues in the health
      humanities, such as interventions in health debates or representations of illness
      and healthcare settings, nourish the cognitive and social conditions needed to
      develop college-level writing skills. The health humanities' emphases on
      interdisciplinarity and suspending judgment also inform students' writing
      abilities. Composition trains students to write rhetorically by considering
      purpose, context, genre, mode, and other factors when addressing an audience.
      This approach to writing helps pre-health humanists communicate intentionally and
      compassionately about health topics as well as the larger issues they call into
      question. Because students enroll in health humanities composition courses at an
      early, formative moment in their studies, they are poised to carry or "transfer"
      their knowledge to other courses, including those that might prepare them for the
      workforce.

PMID- 28516348
TI  - Sclerosing Mucoepidermoid Carcinoma of the Submandibular Gland Presenting as
      Chronic Sialadenitis: A Case Report and Review of Literature.
AB  - Sclerosing mucoepidermoid carcinoma of the salivary gland (SMEC) is a rare
      subtype of mucoepidermoid carcinoma (MEC), first described in 1987 by Chan and
      Saw. As far as we are aware, only 30 cases have been published since then. Most
      cases were located in the parotid gland with some cases described in the
      submandibular and minor salivary glands. SMEC typically presents as a long
      standing mass, with a non-specific enhancing appearance on imaging and is often
      non-diagnostic on fine needle aspiration, making pre-operative diagnosis very
      difficult. It is characterised by dense sclerosis within an otherwise typical
      MEC, frequently with lymphoid proliferation and eosinophils at the periphery. The
      histological diagnosis of SMEC can be challenging, as the sclerosis may obscure
      the other morphological features, which can lead to misdiagnosis. Grading can
      also be difficult, and the prognostic value of grading for SMEC remains unclear.
      Herein is described a new case of SMEC, presenting clinically as chronic
      sialadenitis in the left submandibular gland of a 41 year old male. A brief
      literature review and the issues surrounding diagnosis and grading are also
      discussed.

PMID- 28516349
TI  - Anthropogenic activities and coastal environmental quality: a regional
      quantitative analysis in southeast China with management implications.
AB  - Regional analysis of environmental issues has always been a hot topic in the
      field of sustainable development. Because the different levels of economic
      growth, urbanization, resource endowments, etc. in different regions generate
      apparently different ecological responses, a better description and comparison
      across different regions will provide more valuable implications for ecological
      improvement and policymaking. In this study, seven typical bays in southeast
      China that are a rapid developing area were selected to quantitatively analyze
      the relationship between socioeconomic development and coastal environmental
      quality. Based on the water quality data from 2007 to 2015, the multivariate
      statistical method was applied to analyze the potential environmental risks and
      to classify the seven bays based on their environmental quality status. The
      possible variation trends of environmental indices were predicted based on the
      cross-regional panel data by Environmental Kuznets Curve. The results showed that
      there were significant regional differences among the seven bays, especially
      Quanzhou, Xiamen, and Luoyuan Bays, suffered from severer artificial disturbances
      than other bays, despite their different development patterns. Socioeconomic
      development level was significantly associated with some water quality indices
      (pH, DIN, PO4-P); the association was roughly positive: the areas with higher GDP
      per capita have some worse water quality indices. In addition, the decreasing
      trend of pH values and the increasing trend of nutrient concentration in the
      seven bays will continue in the foreseeable future. In consideration of the
      variation trends, the limiting nutrient strategy should be implemented to
      mitigate the deterioration of the coastal environments.

PMID- 28516350
TI  - Evaluation of vascular effect of arsenic using in vivo assays.
AB  - Arsenic (As) is an abundant toxicant present in groundwater and soil in various
      parts of the world including eastern part of India. The epidemiological studies
      have shown that arsenic exposure is linked to developmental defects and
      miscarriage. Placenta is known to utilize vasculogenesis to develop its
      vasculature circulation. The effects of four different doses of sodium meta
      arsenite (0, 10, 20, 75, and 150 ppm) were assessed on the vascular structure
      using two different in vivo models, i.e., Matrigel and chorioallantoic membrane
      (CAM) assay. For the Matrigel assay, mice were exposed to different doses of
      arsenic through drinking water for 1 month. Placenta and Matrigel plug (which was
      inserted on gestational day (GD 0.5)) were removed on GD 14. Similar arsenic
      concentration was used in CAM assay to observe the effect of vessel development
      in hen's eggs. The CAM assay outcome evaluated by Angiosys software showed that
      arsenic exposure reduced the total and mean tubule length in all the arsenic
      treated groups. The percentage tubule inhibition was declined significantly in
      20, 75, and 150 ppm arsenic-treated groups as evaluated by ImageJ software.
      Analysis of the CAM outcome by both the image analysis software indicated the
      adverse effect of arsenic on the tubules. Further, a significant higher blood
      vessel density in 10 ppm and lower vessel density in 20, 75, and 150 ppm arsenic
      exposed mice were also observed in Matrigel plug assay. The placental hypertrophy
      and dysplasia especially in the labyrinth zone (vasculature) were noted in
      placenta of arsenic-treated mice. The study indicated that higher arsenic
      exposures inhibited the angiogenesis which was dose-dependent in both CAM and
      Matrigel assay and altered structural morphology of placenta. However, no
      inhibition of blood vessels was noted at lower, i.e., 10 ppm of arsenic-treated
      group.

PMID- 28516353
TI  - Physical hazard safety awareness among healthcare workers in Tanta university
      hospitals, Egypt.
AB  - Hospital workers are exposed to many occupational hazards that may threaten their
      health and safety. Physical hazards encountered in hospital working environment
      include temperature, illumination, noise, electrical injuries, and radiation. To
      assess the awareness of healthcare workers (HCWs) about physical hazards in Tanta
      university hospitals, this cross-sectional study included 401 HCWs (physicians,
      nurses, technicians, and workers) from seven departments (general surgery,
      orthopedics, radiology, ophthalmology, kitchen, incinerator, and laundry). Data
      were collected through interview questionnaire to assess six types of physical
      hazards (noise, electric hazards, temperature, radiation, fire, and lighting,).
      Most of the physicians (63.7%) were aware of the level of noise. All physicians,
      nurses, technicians, and majority of workers reported that hearing protective
      devices were not available, and all HCWs reported that periodic hearing
      examination was not performed. Most of the nurses (75.2%) and workers (68.5%) did
      not attended emergency training, and more than two thirds of all HCWs were not
      briefed about emergency evacuation. Most HCWs were not given appropriate
      radiation safety training before starting work (88% of workers, 73.7% of nurses,
      65.7% of physicians, and 68.3% of technicians). The majority of physicians,
      nurses, and technicians (70.5, 65.4, and 53.7%) denied regular environmental
      monitoring for radiation level inside work place. Health education programs on
      health and safety issues regarding physical hazards should be mandatory to all
      healthcare workers to improve their awareness and protect them from undue
      exposures they may face due to lack of adequate awareness and knowledge. There is
      urgent need of expanding the occupational healthcare services in Egypt to cover
      all the employees as indicated by the international recommendations and the
      Egyptian Constitution, legislation, and community necessity.

PMID- 28516351
TI  - Analysis of some metallic elements and metalloids composition and relationships
      in parasol mushroom Macrolepiota procera.
AB  - The aim of the study was to characterise the multi-elemental composition and
      associations between a group of 32 elements and 16 rare earth elements collected
      by mycelium from growing substrates and accumulated in fruiting bodies of
      Macrolepiota procera from 16 sites from the lowland areas of Poland. The elements
      were quantified by inductively coupled plasma quadrupole mass spectrometry using
      validated method. The correlation matrix obtained from a possible 48 * 16 data
      matrix has been used to examine if any association exits between 48 elements in
      mushrooms foraged from 16 sampling localizations by multivariate approach using
      principal component (PC) analysis. The model could explain up to 93% variability
      by eight factors for which an eigenvalue value was >=1. Absolute values of the
      correlation coefficient were above 0.72 (significance at p < 0.05) for 43
      elements. From a point of view by consumer, the absolute content of Cd, Hg, Pb in
      caps of M. procera collected from background (unpolluted) areas could be
      considered elevated while sporadic/occasional ingestion of this mushroom is
      considered safe. The multivariate functional analysis revealed on associated
      accumulation of many elements in this mushroom. M. procera seem to possess some
      features of a bio-indicative species for anthropogenic Pb but also for some
      geogenic metals.

PMID- 28516352
TI  - Air pollution and respiratory health among diabetic and non-diabetic subjects in
      Pune, India-results from the Wellcome Trust Genetic Study.
AB  - Diabetics may be more vulnerable to the harmful effects of ambient air pollutants
      than healthy individuals. But, the risk factors that lead to susceptibility to
      air pollution in diabetics have not yet been identified. We examined the effect
      of exposure to ambient PM10 on chronic symptoms and the pulmonary function tests
      (PFT) in diabetic and non-diabetic subjects. Also, to investigate possible
      determinants of susceptibility, we recruited 400 type 2 diabetic and 465 healthy
      subjects who were investigated for chronic respiratory symptoms (CRSs) and then
      underwent measurement of forced vital capacity (FVC) and forced expiratory volume
      1 (FEV1) according to standard protocol. Percent predicted FEV1 and FVC (FEV1%
      and FVC%, respectively) for each subject were calculated. Particulate matter
      (PM10) concentrations at residence place of subjects were estimated using AERMOD
      dispersion model. The association between PM10 and CRSs was explored using
      logistic regression. We also used linear regression models controlling for
      potential confounders to study the association between chronic exposure to PM10
      and FEV1% and FVC%. Prevalence of current wheezing, allergy symptom, chest
      tightness, FEV1/FVC <70%, and physician-diagnosed asthma and COPD was
      significantly higher among diabetic subjects than non-diabetics. There was no
      significant difference between percent predicted value of PFT among diabetic and
      non-diabetic subjects (P < 0.05). We estimated that 1 SD increase in PM10
      concentration was associated with a greater risk of having dyspnea by 1.50-fold
      (95% CI, 1.12-2.01). Higher exposure to PM10 concentration was also significantly
      associated with lower FVC%. The size of effect for 1 SD MUg/m3 (=98.38) increase
      in PM10 concentration was 3.71% (95% CI, 0.48-4.99) decrease in FVC%. In
      addition, we indicated that strength of these associations was higher in
      overweight, smoker, and aged persons. We demonstrated a possible contribution of
      air pollution to reduced lung function independent of diabetes status. This study
      suggests that decline in exposure may significantly reduce disease manifestation
      as dyspnea and impaired lung function. We conduct that higher BMI, smoking, and
      older age were associated with higher levels of air pollution effects.

PMID- 28516354
TI  - Characterization, partitioning, and potential ecological risk quantification of
      trace elements in coal fly ash.
AB  - Coal-based thermal power plants are the major source of power generation in
      India. Combustion of coal gives rise to by-products such as fly ash (FA) in huge
      quantities. The current study focuses on physico-chemical and mineralogical
      characterization and risk evaluation of FA, generated from five thermal power
      plants (TPPs) of India. The coal, and corresponding FA and bottom ash (BA) were
      further analyzed for trace elements in order to observe the enrichment and
      partitioning behavior of elements. The environmental risk assessment of trace
      elements in FA was performed in accordance with geoaccumulation index (I geo) and
      potential ecological risk index (PERI). The results demonstrated that FA was
      enriched predominantly in SiO2, Al2O3, and Fe2O3 along with small concentrations
      of CaO and MgO. The mineral phases identified in FA were quartz, mullite,
      hematite, and magnetite. Elemental characterization indicated that the metals
      were more enriched in FA as compared to coal and BA. The concentrations of trace
      elements, Cr, Pb, Hg, and As in FA (TPPs), varied from 12.59-24.28, 22.68-43.19,
      <0.0001-2.29, and 0.08-3.39 mg/kg, respectively. Maximum enrichment ratio (ER)
      was observed for Pb (5.21) in TPP3 FA. Hg in TPP1 showed the highest partition
      ratio (PR) value. I geo values for metals were mostly below zero. The PERI values
      indicated moderate risk from TPP4 FA and low risk from TPP1, TPP2, TPP3, and TPP5
      FA to the environment, according to the threshold values provided.

PMID- 28516355
TI  - Valve movement of three species of North American freshwater mussels exposed to
      elevated carbon dioxide.
AB  - Freshwater mussels are at-risk taxa and may be exposed to high levels of carbon
      dioxide (CO2) because of the potential use of CO2 to control the movement of
      invasive aquatic fish species. One potential behavioral response to a change in
      the partial pressure of CO2 (pCO2) may be altered valve movement. In this study,
      three species of mussels were fitted with modified sensors and exposed to two
      regimes of pCO2 to define thresholds of impaired valve movement. The first
      experiment demonstrated that Pyganodon grandis were much more tolerant to rising
      pCO2 relative to Lampsilis siliquoidea (acute closure at ~200,000 MUatm in
      comparison to ~80,000 MUatm). The second experiment consisted of monitoring
      mussels for 6 days and exposing them to elevated pCO2 (~70,000 MUatm) over a 2
      day period. During exposure to high pCO2, Lampsilis cardium were open for nearly
      the entire high pCO2 period. Conversely, P. grandis were closed for most of the
      period following exposure to high pCO2. For L. siliquoidea, the number of
      closures decreased nearly 40-fold during high pCO2. The valve movement responses
      observed suggest species differences, and exposure to elevated pCO2 requires a
      reactive response.

PMID- 28516356
TI  - Morphology, ultrastructure, and element uptake in Calophyllum brasiliense
      Cambess. (Calophyllaceae J. Agardh) seedlings under cadmium exposure.
AB  - Cadmium (Cd) is a metal known for its genotoxicity and cytotoxicity, much
      concerned for its potential environmental and human health impacts. This study
      evaluates the toxic effect of Cd in Calophyllum brasiliense plants. The plants
      were cultivated for 30 days in full nutrient solution in order to adapt, and for
      15 days in nutrient solution without Cd or with 4, 8, 16, and 32 MUmol Cd L-1.
      Anatomical analysis of the leaf showed no significant effects of Cd on epidermal
      thickness in abaxial and adaxial sides, palisade, and spongy parenchyma.
      Contrastingly, changes were noticed in the ultrastructural level in the leaf
      mesophyll cells as rupture of the membrane of chloroplasts and disorganization of
      the thylakoid membranes, in starch grains and in mitochondria with rupture of the
      membrane and invagination of the nuclear membrane. Electron dense materials into
      cells of the cortex and vascular bundle were also observed. In the cells of the
      root system, the observed ultrastructural changes were disruption of the cell
      wall and electron dense material deposition in the cortex cells and vascular
      region. Cd accumulated in roots with low translocation into shoot. Cd toxicity
      also affected the photosynthetic activity, inducing stomatal closure and
      photosynthetic assimilation reduction and the instantaneous carboxylation
      efficiency, drastically reducing the leaf transpiration. The nutrient content in
      the stem and root was variable, according to Cd increase in nutrient solution.
      Based on the experimental evidence, it can be concluded that C. brasiliense has
      potential to bioconcentrate high Cd levels in the root system.

PMID- 28516357
TI  - Reducing greenhouse gas emissions: a duopoly market pricing competition and
      cooperation under the carbon emissions cap.
AB  - This article studies the price competition and cooperation in a duopoly that is
      subjected to carbon emissions cap. The study assumes that in a departure from the
      classical Bertrand game, there is still a market for both firms' goods regardless
      of the product price, even though production capacity is limited by carbon
      emissions regulation. Through the decentralized decision making of both firms
      under perfect information, the results are unstable. The firm with the lower
      maximum production capacity under carbon emissions regulation and the firm with
      the higher maximum production capacity both seek market price cooperation. By
      designing an internal carbon credits trading mechanism, we can ensure that the
      production capacity of the firm with the higher maximum production capacity under
      carbon emissions regulation reaches price equilibrium. Also, the negotiation
      power of the duopoly would affect the price equilibrium.

PMID- 28516358
TI  - Mechanistic Modeling of the Pharmacodynamic and Pharmacokinetic Relationship of
      Tissue Factor Pathway Inhibitor-Neutralizing Antibody (BAY 1093884) in Cynomolgus
      Monkeys.
AB  - BAY 1093884 is a fully human monoclonal antibody against the tissue factor
      pathway inhibitor (TFPI) in development as prophylaxis in patients with
      hemophilia with or without inhibitors. In vitro, BAY 1093884 binds to human,
      mouse, and monkey TFPI. The objective of this study was to find a pharmacodynamic
      (PD) biomarker after administration of BAY 1093884 to normal monkeys. In monkey
      plasma, BAY 1093884 exhibited an IC50 (concentration that inhibits 50%) of 4.65
      and 6.19 nM for free TFPI and diluted prothrombin time (dPT), respectively. The
      BAY 1093884 pharmacokinetic (PK) profile and its PD effects on dPT and free TFPI
      levels were assessed after intravenous and subcutaneous administration of BAY
      1093884 (5 and 20 mg/kg) to female cynomolgus monkeys. Free TFPI concentrations
      in plasma decreased rapidly and increased to baseline in a dose-dependent manner.
      dPT clotting time was shortened and correlated with free TFPI levels and drug
      concentration in plasma, demonstrating the relationship between PD activities
      (dPT clotting time and free TFPI levels) and drug concentration. BAY 1093884
      exhibited nonlinear PK, and a target-mediated drug disposition model was used to
      characterize the BAY 1093884 versus TFPI concentration-response relationship. We
      concluded that a mechanism-based PK/PD binding model could be useful for
      predicting human response to BAY 1093884. For the first-in-human study,
      measurement of free TFPI will be included as part of the dose-escalation design.

PMID- 28516360
TI  - Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models
      of FLT3 mutated acute myeloid leukemia.
AB  - Advances in the understanding of the molecular basis for acute myeloid leukemia
      (AML) have generated new potential targets for treatment. Fms-like tyrosine
      kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations
      in this gene are associated with poor overall survival. AXL plays a role in the
      activation of FLT3 and has been implicated in the pathogenesis of AML. The
      studies reported here evaluated the ability of a novel FLT3/AXL inhibitor,
      gilteritinib, to block mutated FLT3 in cellular and animal models of AML. Initial
      kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was
      highly selective for both FLT3 and AXL while having weak activity against c-KIT.
      Gilteritinib demonstrated potent inhibitory activity against the internal tandem
      duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using
      MV4-11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3.
      Gilteritinib also inhibited FLT3-F691 mutations, although to a lesser degree, in
      these assays. Furthermore, gilteritinib decreased the phosphorylation levels of
      FLT3 and its downstream targets in both cellular and animal models. In vivo,
      gilteritinib was distributed at high levels in xenografted tumors after oral
      administration. The decreased FLT3 activity and high intratumor distribution of
      gilteritinib translated to tumor regression and improved survival in xenograft
      and intra-bone marrow transplantation models of FLT3-driven AML. No overt
      toxicity was seen in mouse models treated with gilteritinib. These results
      indicate that gilteritinib may be an important next-generation FLT3 inhibitor for
      use in the treatment of FLT3 mutation-positive AML.

PMID- 28516359
TI  - Evolution of Choice of Solubility and Dissolution Media After Two Decades of
      Biopharmaceutical Classification System.
AB  - The introduction of the biopharmaceutics drug classification system
      (Biopharmaceutics Classification System (BCS)), in 1995, provided a simple way to
      describe the biopharmaceutics behavior of a drug. Solubility and permeability are
      among the major parameters, which determine the fraction dose absorbed of a drug
      substance and consequently its chances to be bioavailable. The purpose of this
      review is to summarize the evolution of the media used for determining solubility
      and dissolution and how this can be used in modern drug development. Over the
      years, physiologically adapted media and buffers were introduced with the
      intention to better predict the in vivo solubility and dissolution of drug
      substances. Water, buffer solutions, compendial media, micellar solubilization
      media, and biorelevant media are reviewed. At this time point, there is no
      universal medium available which can be used to predict every drug substance's
      solubility or a drug product's in vivo dissolution behavior. However, there have
      been many improvements and additions made to media to optimize their in vivo
      predictability; for example, the current phosphate concentrations in buffers seem
      to be too high to correlate with the carbonate buffer concentrations in vivo.
      Biorelevant media were updated to correlate them better with the composition of
      human intestinal fluids. The BCS was introduced into regulatory sciences as a
      scientific risk management tool to waive bioequivalence studies under certain
      conditions. Today's different guidance documents define the dose-solubility ratio
      differently. As shown for amoxicillin, this can cause more confusion than
      certainty for globally operating companies. Harmonization of BCS guidelines is
      highly desirable.

PMID- 28516362
TI  - Evidence for the existence of a communication between the eye and the brain?

PMID- 28516361
TI  - Familiarity with Own Population's Appearance Influences Facial Preferences.
AB  - Previous studies have found that individuals from rural areas in Malaysia and in
      El Salvador prefer heavier women than individuals from urban areas. Several
      explanations have been proposed to explain these differences in weight
      preferences but no study has explored familiarity as a possible explanation. We
      therefore sought to investigate participants' face preferences while also
      examining the facial characteristics of the actual participants. Our results
      showed that participants from rural areas preferred heavier-looking female faces
      than participants from urban areas. We also found that the female faces from the
      rural areas were rated as looking heavier than the female faces from the urban
      areas. Our findings are consistent with the hypothesis that familiarity may be
      contributing to the differences found in face preferences between rural and urban
      areas given that people from rural and urban areas are exposed to different
      faces.

PMID- 28516363
TI  - Posterior reversible encephalopathy syndrome presenting in the anterior
      circulation with malignant intracranial hypertension requiring surgical
      decompression: a case report and literature review.
AB  - Posterior reversible encephalopathy syndrome (PRES) is thought to result from
      endothelial dysfunction and breakdown of the blood-brain barrier with subsequent
      vasogenic edema. Abrupt hypertension has been identified as one of its risk
      factors. We present a rare case of PRES in the anterior circulation with sudden
      onset of left hemiparesis and rapid neurological deterioration on the basis of
      hypertensive crisis. Due to refractory intracranial hypertension, the patient
      required emergent right decompressive craniectomy. Further investigations,
      including a biopsy, revealed an atypical form of PRES. This case illustrates the
      importance of aggressive medical and early surgical management to prevent
      permanent neurological deficits.

PMID- 28516365
TI  - Clipping of ruptured intracranial aneurysms in a hybrid room environment-a case
      control study.
AB  - BACKGROUND: Hybrid room treatment (HRT) provides the surgeon immediate
      intraoperative angiography control of aneurysm occlusion and vessel patency.
      Since it is relatively resource demanding, in clinical routine HRT is reserved
      for elective cases. However, since its introduction in our department in 2008,
      several random cases of ruptured intracranial aneurysms (IAs) have been treated
      in the HR. This study aims to compare the clinical and radiological outcomes of
      these cases with cases treated conventionally using a matched pair analysis.
      METHODS: Twenty (20%) consecutive patients with ruptured IA treated by
      microsurgical clipping in the HR between 2009 and 2015 were retrospectively
      matched with "conventionally" (C) treated patients (overall n = 101). Clinical
      and radiological outcome variables were assessed and compared. RESULTS: Despite a
      trend in favor of the HR group, no significant difference between both matched
      groups (HR vs. C) could be demonstrated regarding the functional outcome
      (upper/lower good recovery 16/20 vs. 17/20, p > 0.05), frequency of clipping
      related vascular insults on CT scans (0/20 vs. 3/20, p > 0.05), aneurysm remnant
      rate on postoperative angiography (1/20 vs. 4/20, p > 0.05) and retreatment rate
      (0/20 vs. 1/20, p > 0.05). When cumulating all outcome events by a scoring
      system, however, the HR cohort showed a significantly lower occurrence of events
      (p < 0.05). In three cases co-treatment by an endovascular approach was performed
      in the HR cohort. CONCLUSION: In this relatively small cohort, a matched pair
      analysis revealed a discrete but not significant tendency toward a lower
      frequency of aneurysm remnants and clipping-related vascular insults in the HR
      cohort. However, HR cohort patients benefited from direct endovascular co
      treatment in selected cases.

PMID- 28516367
TI  - Appropriate or inappropriate ICD shock; what is the post-shock rhythm?

PMID- 28516364
TI  - Preserving normal facial nerve function and improving hearing outcome in large
      vestibular schwannomas with a combined approach: planned subtotal resection
      followed by gamma knife radiosurgery.
AB  - OBJECTIVE: To perform planned subtotal resection followed by gamma knife surgery
      (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at
      an optimal functional outcome for facial and cochlear nerves. METHODS: Patient
      characteristics, surgical and dosimetric features, and outcome were collected
      prospectively at the time of treatment and during the follow-up. RESULTS: A
      consecutive series of 32 patients was treated between July 2010 and June 2016.
      Mean follow-up after surgery was 29 months (median 24, range 4-78). Mean
      presurgical tumor volume was 12.5 cm3 (range 1.47-34.9). Postoperative status
      showed normal facial nerve function (House-Brackmann I) in all patients. In a
      subgroup of 17 patients with serviceable hearing before surgery and in which
      cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained
      serviceable hearing. Among them, 13 had normal hearing (Gardner-Robertson class
      1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean
      duration between surgery and GKRS was 6.3 months (range 3.8-13.9). Mean tumor
      volume at GKRS was 3.5 cm3 (range 0.5-12.8), corresponding to mean residual
      volume of 29.4% (range 6-46.7) of the preoperative volume. Mean marginal dose was
      12 Gy (range 11-12). Mean follow-up after GKRS was 24 months (range 3-60).
      Following GKRS, there were no new neurological deficits, with facial and hearing
      functions remaining identical to those after surgery in all patients. Three
      patients presented with continuous growth after GKRS, were considered failures,
      and benefited from the same combined approach a second time. CONCLUSION: Our data
      suggest that large VS management, with planned subtotal resection followed by
      GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve
      and a high level of cochlear nerve functions to be retained. Our functional
      results with this approach in large VS are comparable with those obtained with
      GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to
      fully evaluate this approach, especially regarding tumor control.

PMID- 28516366
TI  - Patient-Centered Outcomes in Food Allergy.
AB  - PURPOSE OF REVIEW: Food allergy prevalence is increasing very rapidly, causing a
      significant disease burden. The threat of severe allergic reactions occurring
      unexpectedly and in settings that are not equipped to recognize and treat
      anaphylaxis is a constant source of worry for individuals and families with food
      allergies. Inadequate knowledge and understanding in the community significantly
      impairs the overall quality of life of these individuals and families.
      Additionally, families face challenges in finding and affording appropriate
      allergen-free foods. RECENT FINDINGS: Advancements have been made in
      understanding the impact of food allergies on patient-centered outcomes such as
      quality of life and economic impact, and attempts have been made to develop tools
      to assess patient-centered variables. Innovative national and regional
      initiatives are helping to spread awareness of the disease condition and to
      create resources, including access to allergen-free foods. While there is a
      growing momentum toward recognition of food allergic disorders as a condition
      that profoundly impacts activities of daily living, greater effort needs to be
      expounded to develop validated tools and interventions that can adequately
      address these issues.

PMID- 28516368
TI  - Appropriate or inappropriate ICD shock; what is the post-shock rhythm?

PMID- 28516370
TI  - Health literacy skills and the benefits of cardiovascular disease prevention.

PMID- 28516369
TI  - Management of elderly patients with a non-ST-segment-elevation acute coronary
      syndrome.
AB  - Elderly patients with an acute coronary syndrome are underrepresented in
      randomised controlled trials. Neither the European Society of Cardiology nor the
      American Heart Association/American College of Cardiology acute coronary syndrome
      guidelines provide specific recommendations for elderly patients. However,
      elderly patients are at higher thrombotic and bleeding risk compared with younger
      patients leading to difficulties in choosing the optimal treatment. In this
      review, we discuss the uncertainties we encounter in treating elderly patients
      with non-ST-elevation acute coronary syndrome and suggest treatment options based
      on the existing literature.

PMID- 28516371
TI  - Perforated emphysematous cholecystitis managed by endoscopic transpapillary
      gallbladder drainage.
AB  - An 88-year-old woman with dementia was diagnosed as having perforated
      emphysematous cholecystitis with localized peritonitis. Because she was at high
      risk for surgery, gallbladder drainage was required before surgery. Endoscopic
      transpapillary gallbladder drainage instead of percutaneous transhepatic biliary
      drainage was performed because bile could leak from the puncture site to free
      space around the perforated gallbladder. After the insertion of a nasobiliary
      drainage tube, the gallbladder was drained and cleaned with saline solution.
      Subsequently, a nasobiliary drainage tube was replaced with a double-pigtail
      stent because she was at high risk of dislodging the nasobiliary drainage tube.
      Although clinical improvement was observed, she was treated conservatively
      without surgery. She was followed up for 6 months without developing
      cholecystitis. For perforated cholecystitis without developing panperitonitis,
      endoscopic transpapillary gallbladder drainage would be an effective option as a
      bridge to surgery for the initial treatment and as an alternative to surgery for
      long-term management for a later treatment. This is the first reported case of
      perforated emphysematous cholecystitis with localized peritonitis treated with
      endoscopic transpapillary gallbladder drainage.

PMID- 28516372
TI  - Does thyroid dysfunction increase the risk of breast cancer? A systematic review
      and meta-analysis.
AB  - PURPOSE: To investigate the relationship between hypothyroidism, hyperthyroidism,
      thyroid hormone replacement, and the risk of breast cancer. METHODS: We searched
      the PubMed, Cochrane Library, EMbase, Web of Science, and China Biology Medicine
      (CBM) databases through June 2016 to identify researches that assessed the
      relationship between thyroid dysfunction and the risk of breast cancer together
      with the impact of thyroid hormone substitution treatment on incidence of breast
      cancer. Quality of evidence was assessed per outcome, using GRADE. RESULTS: A
      total of 13 population-based studies including 24,808 participants were
      identified as eligible for this meta-analysis. A meta-analysis of 12 researches
      illustrated that hypothyroidism was not related to the risk for breast cancer
      [odds ratio (OR) = 0.83, 95% confidence interval (CI) 0.64-1.08, P = 0.162]. 10
      researches illustrated that hyperthyroidism was also not related to the risk of
      breast cancer (OR = 1.03, 95% CI 0.83-1.30, P = 0.767). The impact of therapy was
      evaluated in six researches; there was no proof of a relationship between thyroid
      hormone substitution treatment and breast cancer with an overall OR of 0.83 (95%
      CI 0.57-1.21, P = 0.965). CONCLUSIONS: Our meta-analysis illustrated that thyroid
      dysfunction may not be related to increased risk of breast cancer as well as the
      thyroid hormone substitution treatment did not reduce the incidence of breast
      cancer; while this study has some confounders that might weaken the results of
      this meta-analysis, we believe that the findings provide valuable information for
      stakeholders concerned with outcomes in patients with thyroid dysfunction.

PMID- 28516373
TI  - Class side effects: decreased pressure in the lower oesophageal and the pyloric
      sphincters after the administration of dopamine antagonists, neuroleptics, anti
      emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.
AB  - The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides
      unresolved issues of anti-emetic neuroleptic application in both patients and
      experimental studies. Therefore, in a 1-week study, we examined the pressures
      within the lower oesophageal and the pyloric sphincters in rats [assessed
      manometrically (cm H2O)] after dopamine neuroleptics/prokinetics, L-NAME, L
      arginine and stable gastric pentadecapeptide BPC 157 were administered alone
      and/or in combination. Medication (/kg) was given once daily intraperitoneally
      throughout the 7 days, with the last dose at 24 h before pressure assessment.
      Given as individual agents to healthy rats, all dopamine antagonists (central
      [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50
      mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine
      (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone
      (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within
      both sphincters. As a common effect, this decreased pressure was rescued, dose
      dependently, by BPC 157 (10 ug, 10 ng) (also note that L-arginine and L-NAME
      given together antagonized each other's responses). With haloperidol, L-NAME
      worsened both the lower oesophageal and the pyloric sphincter pressure, while L
      arginine ameliorated lower oesophageal sphincter but not pyloric sphincter
      pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally
      had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was
      opposed by L-arginine. All these effects were further reversed towards a stronger
      beneficial effect, close to normal pressure values, by the addition of BPC 157.
      In addition, NO level was determined in plasma, sphincters and brain tissue.
      Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol
      increased NO levels (in both sphincters, the plasma and brain), consistently
      producing increased TBARS levels in the plasma, sphincters and brain tissues.
      These effects were all counteracted by BPC 157 administration. In conclusion, we
      revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect
      of decreased pressure in sphincters and the dopamine/NO-system/BPC 157
      relationship.

PMID- 28516375
TI  - Effects of Bothrops alternatus venom in zebrafish: a histopathological study.
AB  - Zebrafish is an excellent model organism for studying tissue alterations caused
      by Bothrops alternatus venom (BAV) and for screening new anti-venom drugs. To
      study tissue alterations following exposure to BAV and the roles that
      glucocorticoids play in these tissue reactions, zebrafish were randomly divided
      into five groups: the free injection control group (FIC), the phosphate-buffered
      saline injection control group (PIC), the venom injected group (VI), the group
      treated with dexamethasone 1 h before venom injection (D1hBVI) and the group
      treated with dexamethasone 1 h after venom injection (D1hAVI). The concentration
      of BAV injected was 0.13 mg/mL and each fish received an injection of 20 MUL.
      Body weight measurements and histopathological characteristics of the gills,
      kidneys, liver, and intestine were determined. Histopathological analyses showed
      necrosis, inflammation and weight gain in animals that received BAV. The
      histological alteration indices of the gills, liver, kidneys, and intestines were
      statistically higher in the animal groups treated with BAV. These alteration
      indices were lower in the D1hBVI and D1hAVI groups compared to the group treated
      with BAV alone. The D1hBVI group is presented with minor alterations. A
      significant difference in the histological alterations index was observed in the
      intestinal tissue of the FIC group compared to the PIC group. Cumulatively,
      zebrafish may serve as a useful biomarker for alterations induced by BAV.
      Interestingly, dexamethasone reduced the damage caused by BAV in the organs
      studied, which suggests that zebrafish might be useful for screening new drugs
      that can mitigate tissue damage caused by snakebites.

PMID- 28516377
TI  - The Influence of Sitagliptin on Treatment-Related Quality of Life in Patients
      with Type 2 Diabetes Mellitus Receiving Insulin Treatment: A Prespecified Sub
      Analysis.
AB  - INTRODUCTION: Treatment-related quality of life (QOL) is an important aspect of
      diabetes management. Here, we investigated the influence of sitagliptin, a
      dipeptidyl peptidase-4 inhibitor, on treatment-related QOL in patients with type
      2 diabetes mellitus treated with insulin. METHODS: This was a prespecified sub
      analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation
      (SPIKE). The study population consisted of 71 subjects in the sitagliptin group,
      and 62 subjects in the conventional group who were treated with insulin. Patients
      of the sitagliptin group were started on sitagliptin in addition to ongoing
      insulin therapy. In the conventional group, either increasing the dose of current
      insulin therapy or the addition of oral hypoglycemic agents other than dipeptidyl
      peptidase-4 inhibitors was allowed to achieve glycemic control. Treatment-related
      QOL was evaluated before and 104 weeks after the initiation of the study using
      the Diabetes Therapy-Related QOL Questionnaire 7 (DTR-QOL7). RESULTS: Forty-five
      out of 71 subjects in the sitagliptin group and 41 out of 62 subjects in the
      conventional group filled out the QOL questionnaire at week 104. The DTR-QOL7
      score at week 104 was significantly increased from baseline in the sitagliptin
      group, while that in the conventional group was not changed. However, the changes
      in score did not differ between the two groups. Change in HbA1c was negatively
      associated with change in score. CONCLUSIONS: Our data suggest that sitagliptin
      added to insulin treatment was comparable to other treatments in terms of its
      impact on treatment-related QOL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: UMIN000007396. FUNDING: Mitsubishi Tanabe Pharma Co., Ono
      Pharmaceutical Co., and Novo Nordisk.

PMID- 28516374
TI  - Role of LPS-elicited signaling in triggering gastric mucosal inflammatory
      responses to H. pylori: modulatory effect of ghrelin.
AB  - Infection with Helicobacter pylori is a primary culprit in the etiology of
      gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a
      potent endotoxin responsible for triggering a pattern of the mucosal inflammatory
      responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4
      (TLR4) leads to initiation of signal transduction events characterized by the
      activation of mitogen-activated protein kinase (MAPK) cascade, induction of
      phosphoinositide-specific phospholipase C (PLC)/protein kinase C
      (PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt.
      These signaling events in turn exert their influence over H. pylori-elicited
      excessive generation of NO and PGE2 caused by the disturbances in nitric oxide
      synthase and cyclooxygenase isozyme systems, increase in epidermal growth factor
      receptor transactivation, and the induction in matrix metalloproteinase-9 (MMP-9)
      release. Interestingly, the extent of gastric mucosal inflammatory response to H.
      pylori is influenced by a peptide hormone, ghrelin, the action of which relays on
      the growth hormone secretagogue receptor type 1a (GHS-R1a)-mediated mobilization
      of G-protein dependent transduction pathways. Yet, the signals triggered by TLR-4
      activation as well as those arising through GHS-R1a stimulation converge at MAPK
      and PLC/PKC/PI3K pathways that form a key integration node for proinflammatory
      signals generated by H. pylori LPS as well as for those involved in modulation of
      inflammation by ghrelin. Hence, therapeutic targeting these signals' convergence
      and integration node could provide a novel and attractive opportunities for
      developing more effective treatments of H. pylori-related gastric disease.

PMID- 28516378
TI  - HIV Prevalence and Related Risk Factors in Men Who Have Sex with Men in Bamako,
      Mali: Findings from a Bio-behavioral Survey Using Respondent-Driven Sampling.
AB  - Using respondent driven sampling, we conducted a cross-sectional bio-behavioral
      survey among men who have sex with men (MSM) in Bamako, Mali. Eligibility
      criteria included age >=18 years and having had sex with another man in the last
      6 months. We enrolled 552 MSM, 99.6% were tested for HIV. MSM in Bamako were
      young (69.6% <=24 years) and educated (63.7% >=secondary). HIV prevalence among
      MSM in Bamako was 13.7; 90.1% of HIV-infected men were unaware of their HIV
      status. Almost one-third had never been tested for HIV. Factors associated with
      higher odds of HIV included younger age, being receptive with last partner,
      condom breaking during anal sex in last 6 months, talking to peer educator about
      HIV, and having sexually transmitted infection symptoms in past year. The results
      suggest the need for enhanced HIV prevention and treatment services targeted at
      MSM in Bamako, with emphasis on repeated HIV testing.

PMID- 28516376
TI  - An Update on the Approach to the Imaging of Brain Tumors.
AB  - PURPOSE OF REVIEW: Neuroimaging plays a critical role in diagnosis of brain
      tumors and in assessment of response to therapy. However, challenges remain,
      including accurately and reproducibly assessing response to therapy, defining
      endpoints for neuro-oncology trials, providing prognostic information, and
      differentiating progressive disease from post-therapeutic changes particularly in
      the setting of antiangiogenic and other novel therapies. RECENT FINDINGS: Recent
      advances in the imaging of brain tumors include application of advanced MRI
      imaging techniques to assess tumor response to therapy and analysis of imaging
      features correlating to molecular markers, grade, and prognosis. This review aims
      to summarize recent advances in imaging as applied to current diagnostic and
      therapeutic neuro-oncologic challenges.

PMID- 28516379
TI  - Panobinostat Enhances Growth Suppressive Effects of Progestin on Endometrial
      Carcinoma by Increasing Progesterone Receptor and Mitogen-Inducible Gene-6.
AB  - Although progestin has been used to treat endometrial hyperplasia and endometrial
      carcinoma (EC), its therapeutic efficacy is limited. In order to improve this,
      the underlining mechanisms of the effects of progestin need to be elucidated in
      more detail. In the present study, we examined the involvement of mitogen
      inducible gene-6 (MIG6), a negative regulator of the EGF receptor, in the
      progestin-mediated growth suppression of endometrial epithelia. The
      immunohistochemical expression of MIG6 was elevated in the early to mid-secretory
      phases of normal endometrium and also with endometrial hyperplasia after
      medroxyprogesterone acetate (MPA) therapy. The addition of progesterone (P4) to
      progesterone receptor (PR)-positive EC cells reduced the viability and induced
      MIG6 messenger RNA (mRNA) and protein expression. The silencing of MIG6 using
      siRNA eliminated the P4-mediated reduction of EC cell viability, indicating that
      MIG6 is an essential downstream component of PR-mediated growth suppression. In
      order to enhance PR-driven signals, we examined the effects of histone
      deacetylase (HDAC) inhibitors because histone acetylation has been shown to
      increase the expression of PR. The addition of three HDAC inhibitors
      (panobinostat, LBH589; trichostatin A, TSA; suberoylanilide hydroxamic acid,
      SAHA) decreased the viability of EC cells and up-regulated the expression of PR
      and MIG6, and these effects were the strongest with LBH589. The addition of
      LBH589 and MPA synergistically decreased the viability and increased apoptosis in
      EC cells. These results indicate that LBH589 has potential as an enhancer of
      progestin therapy via the up-regulation of PR and MIG6.

PMID- 28516380
TI  - Polymyalgia rheumatica in a melanoma patient due to nivolumab treatment.

PMID- 28516381
TI  - Listening to music during shock wave lithotripsy decreases anxiety, pain, and
      dissatisfaction : A randomized controlled study.
AB  - BACKGROUND: We analyzed the effects of music on pain, anxiety, and overall
      satisfaction in patients undergoing a shock wave lithotripsy (SWL) procedure.
      METHODS: A total of 200 patients scheduled to undergo SWL were included in this
      study. Group 1 consisted of 95 patients who listened to music during the SWL
      session while group 2 included 105 patients who did not listen music during the
      procedure. State-Trait Anxiety Inventory (STAI) was used to assess state and
      trait anxiety (STAI-S/T). A visual analog scale (VAS) was used at the end of the
      session in order to assess pain, willingness to repeat the procedure, and overall
      patient satisfaction. Hemodynamic parameters including systolic blood pressure
      (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded before
      and after the session. RESULTS: No statistically significant difference was found
      between the two groups in terms of stone characteristics, SWL parameters, pre-SWL
      STAI-T/S scores, and pre-SWL hemodynamic parameters. Post-SWL STAI-S scores were
      found to be lower in patients who listened to music (p = 0.006). At the end of
      the SWL, VAS scores of pain, satisfaction, and willingness to repeat procedure
      were significantly different in favor of the music group (p = 0.007, p = 0.001, p
      = 0.015, respectively). SBP, DBP, and HR were significantly higher in patients
      who did not listen to music (p = 0.002, p = 0.024, p = 0.001, respectively).
      CONCLUSION: Music can be an ideal adjunctive treatment modality for patients
      undergoing SWL treatment. It has the potential to enhance patient compliance and
      treatment satisfaction by reducing the procedure-related anxiety and pain
      perception.

PMID- 28516383
TI  - Genetic analysis of the Lf1 gene that controls leaflet number in soybean.
AB  - KEY MESSAGE: A high-resolution genetic map that was constructed for the Lf1 
      residing region will provide valuable information for map-based cloning and
      genetic improvement efforts in soybean. Changes in leaf architecture as
      photosynthesis factories remain a major challenge for the improvement of crop
      productivity. Unlike most soybeans, which have compound leaves comprising three
      leaflets, the soybean Lf1 mutant has a high frequency of compound leaves with
      five leaflets in a partially dominant manner. Here, we generated a fine genetic
      map to determine the genetic basis of this multifoliolate leaf trait. A five
      leaflet variant Dusam was found in a recently collected landrace cultivar.
      Phenotypic data were collected from the F2 population of a cross between the
      Dusam and three-leaflet cultivar V94-5152. The mapping results generated using
      public markers indicated that the five-leaflet determining gene in Dusam is an
      allele of the previously studied Lf1 gene on chromosome 8. A high-resolution map
      delimited the genomic region controlling the leaflet number trait to a sequence
      length of 49 kb. AP2 domain-containing Glyma.08g281900 annotated in this 49 kb
      region appeared to be a strong candidate for the Lf1-encoding gene, as members of
      the AP2-type transcription factor family regulate lateral organ development.
      Dusam additionally exhibits visually distinct phenotypes for shattering and seed
      coat cracking traits. However, the two traits were clearly unlinked to the Lf1
      gene in our mapping population. Interestingly, the mapping results suggest that
      the Lf1 gene most likely exerts a pleiotropic effect on the number of seeds per
      pod. Thus, our results provide a strong foundation towards the cloning of this
      compound leaf development gene and marker-assisted selection of the seeds per pod
      trait.

PMID- 28516382
TI  - Early postoperative growth in non-functioning pituitary adenomas; A tool to
      tailor safe follow-up.
AB  - PURPOSE: Non-functioning pituitary adenomas are common, and the treatment and
      follow-up of these patients represent a multidisciplinary challenge. First line
      treatment is transphenoidal surgery, with debulking or total removal of tumour. A
      substantial portion of the tumours relapse after surgery, and there is no
      consensus of how to follow these patients postoperatively. Our aim was to
      characterize the postoperative growth of non-functioning pituitary adenomas and
      correlate it to clinical and paraclinical data. METHODS: We retrospectively
      registered 52 patients operated for non-functioning pituitary adenomas, with four
      or more consecutive MR-investigations not interrupted by secondary treatment.
      Adenoma volumes were estimated by the Cavalieri principle with summation of
      manually drawn areas multiplied by slice interval. Growth curves were modelled
      and tumour volume doubling time was calculated for 39 tumours with regrowth after
      surgery. RESULTS: A total of 13 tumours showed exponential growth, 10 linear
      growth and 16 logistic growth after surgery. The remaining 13 did not show
      regrowth of tumour. Seven of the exponential growing tumours underwent secondary
      surgery, compared to one and two of linear and logistic growing tumours (p =
      0.03), respectively. Initial tumour volume doubling time was significantly lower
      in logistic growing tumours than in exponential growing tumours (p < 0.01). Men
      had tumours with lower tumour volume doubling time than women (p = 0.03). None of
      the tumours demonstrated signs of accelerated growth. CONCLUSION: Residual
      tumours following surgery frequently grow. The logistic growing tumours had the
      fastest initial growth in our cohort. We found no indication of accelerated
      growth, whereby the tumour volume doubling time might be used to predict a "worst
      case" scenario when planning follow-up of these patients.

PMID- 28516384
TI  - A mutant in the CsDET2 gene leads to a systemic brassinosteriod deficiency and
      super compact phenotype in cucumber (Cucumis sativus L.).
AB  - KEY MESSAGE: A novel dwarf cucumber mutant, scp-2, displays a typical BR
      biosynthesis-deficient phenotype, which is due to a mutation in CsDET2 for a
      steroid 5-alpha-reductase. Brassinosteroids (BRs) are a group of plant hormones
      that play important roles in the development of plant architecture, and extreme
      dwarfism is a typical outcome of BR-deficiency. Most cucumber (Cucumis sativus
      L.) varieties have an indeterminate growth habit, and dwarfism may have its value
      in manipulation of plant architecture and improve production in certain
      production systems. In this study, we identified a spontaneous dwarf mutant,
      super compact-2 (scp-2), that also has dark green, wrinkle leaves. Genetic
      analyses indicated that scp-2 was different from two previously reported dwarf
      mutants: compact (cp) and super compact-1 (scp-1). Map-based cloning revealed
      that the mutant phenotype was due to two single nucleotide polymorphism and a
      single-base insertion in the CsDET2 gene that resulted in a missense mutation in
      a conserved amino acid and thus a truncated protein lacking the conserved
      catalytic domains in the predicted steroid 5alpha-reductase protein. Measurement
      of endogenous hormone levels indicated a reduced level of brassinolide (BL, a
      bioactive BR) in scp-2, and the mutant phenotype could be partially rescued by
      the application of epibrassinolide (EBR). In addition, scp-2 mutant seedlings
      exhibited dark-grown de-etiolation, and defects in cell elongation and vascular
      development. These data support that scp-2 is a BR biosynthesis-deficient mutant,
      and that the CsDET2 gene plays a key role in BR biosynthesis in cucumber. We also
      described the systemic BR responses and discussed the specific BR-related
      phenotypes in cucumber plants.

PMID- 28516385
TI  - Conservative/surgical treatment predictors of maternal hydronephrosis: results of
      a single-center retrospective non-randomized non-controlled observational study.
AB  - PURPOSE: To determine the parameters that may help the clinicians decide the best
      suitable treatment method for the pregnant women with symptomatic hydronephrosis
      which will be based on the easily accessible laboratory tests, monitoring methods
      and clinical symptoms. METHODS: Digital data and documents of 246 pregnant women
      with symptomatic hydronephrosis who were hospitalized in our clinic between the
      dates of January 2011 and January 2016 were retrospectively evaluated. All
      patients were statistically evaluated in terms of age, symptomatic maximal
      anterior-posterior diameter of the renal pelvis (MADP), parity, C-reactive
      protein (CRP) level, white blood cell count (WBC), presence of pyuria, growth of
      urine culture, fever, serum urine and creatinine levels, visual analog scale
      (VAS) score of pre- and post-therapy and threatened preterm labor. RESULTS: The
      study includes a total of 211 pregnant women with symptomatic hydronephrosis. In
      the second and third trimester groups, the surgical treatment group statistically
      provided higher levels of CRP, WBC and VAS. Mean MADP in the second trimester of
      the conservative and surgical groups where symptomatic hydronephrosis was on the
      right side was 16.67 +/- 4.67 and 28.68 +/- 7.70 mm, respectively. Mean MADP in
      the third trimester group of the conservative and surgical groups where
      symptomatic hydronephrosis was on the right side was 16.96 +/- 5.96 and 28.85 +/-
      7.64 mm, respectively. CONCLUSIONS: In patients with symptomatic pregnancy
      hydronephrosis, the likelihood of surgical treatment for CRP levels, WBC counts
      and VAS is high.

PMID- 28516387
TI  - A diffusion-weighted imaging informed continuum model of the rabbit triceps surae
      complex.
AB  - The NZ white rabbit is the animal of choice for much experimental work due to its
      muscular frame and similar response to human diseases, and is one of the few
      mammals that have had their genome sequenced. However, continuum-level
      computational models of rabbit muscle detailing fibre architecture are limited in
      the literature, especially the triceps surae complex (gastrocnemius, plantaris
      and soleus), which has similar biomechanics and translatable findings to the
      human. This study presents a geometrical model of the rabbit triceps surae
      informed with diffusion-weighted imaging (DWI)-based fibres. Passive rabbit
      specific material properties are estimated using known muscle deformation
      inferred from magnetic resonance imaging data and dorsiflexion force measured
      with a custom-built rabbit rig and transducer. Muscle shape prediction is
      evaluated against a second rabbit. This study revealed that the triceps surae
      steady-state force post-rigor is close to post-mortem for small deformations but
      increases by a fixed ratio as the deformation increases and can be used to
      evaluate the passive behaviour of muscle. DWI fibre orientation significantly
      influences shape and mechanics during simulated computational muscle contraction.
      The presented triceps surae force and material properties may be used to inform
      the constitutive behaviour of continuum rabbit muscle models used to investigate
      pathology and musculotendon treatments that may be translated to the human
      condition.

PMID- 28516386
TI  - Intergenerational Transmission of Depressive Symptoms: The Role of Parental
      Negative Perceptions and Behaviors.
AB  - This study examined parental proximal processes involving in the
      intergenerational transmission of depressive symptoms from parents to their
      children. Extant literature has predominantly focused on maternal depressive
      symptoms. Yet, the mechanisms that may underlie the transmission of paternal
      depressive symptoms is less often studied. Participants were Chinese parents of
      first-graders (N = 2282). Results of structural equation modeling suggested that
      maternal and paternal depressive symptoms may be transmitted to their children
      through differential processes. Depressive symptoms in mothers, but not in
      fathers, were associated with their negatively-biased perceptions and
      dysfunctional parenting practices, which then predicted depressive symptoms in
      children. Moreover, mothers' depressive symptoms were associated with children's
      depressive symptoms regardless of child gender, whereas fathers' depressive
      symptoms were associated with boys', but not girls', depressive symptoms.
      Findings expand the understandings on parental processes in the intergenerational
      transmission of depressive symptoms in families, the role of paternal depressive
      symptoms in promoting children's depressive symptoms, and who may be at
      particular risks for psychopathology in the face of parental depressive symptoms.

PMID- 28516388
TI  - Effects of Different Selenium Sources on Growth Performance, Antioxidant Capacity
      and Meat Quality of Local Chinese Subei Chickens.
AB  - Despite increasing evidence indicating the essential involvement of selenium (Se)
      on growth performance, antioxidant capacity, and meat quality of commercial
      broilers, the effects of different Se sources on local Chinese Subei chickens is
      unclear. A total of 360 50-day-old male chickens were individually weighed and
      randomly allocated to four treatment groups. Chickens in each of the four groups
      were fed diets supplemented with 0.3 mg Se/kg as sodium Se (SS), Se-enriched
      yeast (SY), selenomethionine (Met-Se), or nano red element Se (Nano-Se) for 40
      days. At the end of the experiment, one bird of approximately average weight from
      each cage was selected and slaughtered, and blood and breast muscles samples were
      collected. The results showed that there was no significant difference in feed
      intake, body weight gain, or feed to gain ratio among treatments (P > 0.05).
      Dietary SY, Met-Se, and Nano-Se supplementation increased the activity of
      glutathione peroxidase in serum and breast muscles and decreased the
      concentration of malondialdehyde in serum and carbonyl in breast muscles compared
      with the SS group (P < 0.05). Moreover, SY, Met-Se, and Nano-Se supplementation
      increased pH45min, total protein solubility, and myofibrillar protein solubility,
      as well as decreased the shear force value compared with the SS group (P < 0.05).
      In addition, birds in the SY and Met-Se groups exhibited lower cooking loss
      compared with the SS group (P < 0.05). In conclusion, organic Se and Nano-Se
      supplementation resulted in an improvement of antioxidant capacity and meat
      quality in local Chinese Subei chickens relative to inorganic Se.

PMID- 28516389
TI  - Microenvironmental Scenario of the Bone Marrow of Inorganic Arsenic-Exposed
      Experimental Mice.
AB  - Exposure to arsenic on a regular basis, mainly through drinking water,
      agricultural pesticide, and sometimes therapeutic dose, results in various
      diseases of different tissues including the bone marrow hematopoietic system.
      Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic
      stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally
      mature blood cells by the support of microenvironmental components. The present
      study has been aimed to understand stem cell microenvironmental status during
      arsenic toxicity and the consequent reflection of dysregulation involving the
      hematopoietic machinery in experimental mice. Swiss albino mice were
      experimentally exposed to 10 MUg arsenic trioxide/g body weight through oral
      gavage and 5 MUg arsenic trioxide/g body weight intraperitoneally for a period of
      30 days. Altered hemogram values in peripheral blood reflected the impaired
      hematopoiesis which was further validated by the reduced BM cellularity along
      with the deviated BM cell morphology as observed by scanning electron microscopy
      post arsenic exposure. The stromal cells were unable to establish a healthy
      matrix and the sustainability of hematopoietic progenitors was drastically
      affected in arsenic-exposed mouse groups, as observed in in vitro explant
      culture. The inability of stromal cells to establish supportive matrix was also
      explained by the decreased adherent colony formation in treated animals.
      Furthermore, the flow cytometric characterization of CXCR4+ and Sca-1+ CD44+
      receptor expressions confirmed the dysregulation in the hematopoietic
      microenvironment. Thus, considering the importance of microenvironment in the
      maintenance of HSPC, it can be concluded that arsenic toxicity causes
      microenvironmental damage, leading to niche derangement and impaired
      hematopoiesis.

PMID- 28516390
TI  - The Identity of "Chromium Malate".
AB  - Recently, several studies on the effects of a compound named "chromium malate,"
      with the proposed formula "Cr2malate3.xH2O" where x = 3.5 or 5, on the health of
      healthy and diabetic rats have appeared. However, the compound is poorly
      characterized, and knowing the identity of this material could be important in
      the interpretation of the previous and of future studies on the effects of this
      compound in animals. Consequently, the synthesis, characterization, and identity
      of this material were explored. A combination of spectroscopic, magnetic, and
      elemental analyses and mass spectral studies reveal that the compound is probably
      a polymer, not a discrete molecule, and does not have the composition previously
      reported. The repeating unit of the polymer possesses an antiferromagnetically
      coupled trinuclear Cr(III) core. The current study suggests that previous reports
      on chromium malate and its effects in animals must be viewed with caution.

PMID- 28516391
TI  - Denial of a sleep deprivation message: situational and dispositional influences
      on message rejection.
AB  - Two studies investigated situational and dispositional influences on rejection of
      a sleep deprivation warning message for young adults. The hassle of protection
      (Study 1) and the self-relevance of the problem (Study 2) were manipulated; the
      disposition to use denial (threat orientation) for warning messages was measured.
      In both studies, it was found that both dispositional denial and the situational
      manipulation (more protection-hassle or self-relevance) showed at least one
      denial effect by reducing perceived susceptibility, perceived severity, or
      credibility. Indirect (mediational) effects were tested with the bootstrap
      method. In Study 1, judgments of credibility and severity mediated the effects of
      the hassle manipulation and denial orientation on message outcomes. In Study 2,
      credibility mediated the effects of the self-relevance manipulation and denial
      orientation on message outcomes of intentions to change and priority given to
      sleep. These studies show that both situational and dispositional sources of
      denial work in similar ways by lowering key message judgments and that the lower
      judgments lead to less priority given to a health risk and lower intentions to
      protect oneself.

PMID- 28516392
TI  - Cavernous sinus thrombosis in a patient with nephrotic syndrome.

PMID- 28516395
TI  - Thoracoscopic partial resection without using a stapler. (complete
      republication).
AB  - Thoracoscopic partial pulmonary resection for small peripheral nodules without
      using a stapler has been introduced to our hospital. After partial resection was
      performed with electrocautery, two different methods of surface sealing were
      used: a coagulation method (C method) with Soft Coagulation alone, and a
      coagulation-suturing method (CS method) with Soft Coagulation combined with
      continuous suturing. The clinical outcomes of the two methods were
      retrospectively compared in this study. The C method was used in 19 lesions of 18
      cases, and the CS method was used in 20 lesions of 19 cases. Primary lung cancer
      was the most frequent diagnosis (22 lesions of 21 cases). There were no
      differences between the two groups in the size and depth of the lesions.
      Operative time was longer with the CS method than with the C method.
      Postoperative air leakage was a complication in 4 cases with the C method, and
      one of them required re-do surgery, whereas only one case with the CS method had
      temporary air leakage. Postoperative computed tomography showed cavitation in 3 C
      method cases and 5 CS method cases, all without related symptoms. There were no
      local recurrences at resected sites. In conclusion, the C method was technically
      easy to perform, but air leakage may be prolonged after surgery. The CS method
      may have the advantage of causing less air leakage than the C method, but
      mastering the technique is important to shorten operative time.

PMID- 28516393
TI  - Plasma MMP2/TIMP4 Ratio at Follow-up Assessment Predicts Disease Progression of
      Idiopathic Pulmonary Arterial Hypertension.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs)
      are of particular interest in the remodeling processes of pulmonary hypertension.
      The aim of this study was to investigate MMP/TIMP ratios of selected biomarkers
      (MMP2, MMP9, TIMP1, TIMP4) at follow-up examination (V2) and their prognostic
      value in patients with idiopathic pulmonary arterial hypertension (iPAH).
      METHODS: Blood samples were taken from iPAH patients during right heart
      catheterization at diagnosis (V1, from 2003 to 2012) and first follow-up
      examination (V2). MMP2, MMP9, TIMP1, and TIMP4 plasma levels at V2 were
      determined by ELISA. Coincident with sample collection hemodynamic, laboratory,
      and clinical parameters were acquired. Additionally, death and clinical worsening
      (CW) events were listed until July 2015. RESULTS: MMP2/TIMP1 and MMP9/TIMP1 did
      not correlate with hemodynamic and clinical parameters. MMP2/TIMP4 showed a good
      correlation with mean pulmonary arterial pressure (mPAP), pulmonary vascular
      resistance, estimated glomerular filtration rate (eGFR), and tricuspid annular
      plain systolic excursion (TAPSE). MMP9/TIMP4 shows good correlation with mPAP and
      eGFR. MMP2/TIMP4 showed significant results in the receiver operating
      characteristics analysis predicting death (AUC = 0.922; p = 0.005) and CW event
      (AUC = 0.818; p = 0.026). Patients above the cut-off values had a significantly
      higher probability to die or experience CW, respectively, estimated by log-rank
      test (p = 0.010 for death; p = 0.032 for CW). CONCLUSIONS: MMP2/TIMP4 ratio was
      detected as a marker of disease severity and right ventricular function as well
      as a predictor for survival and time to clinical worsening and therefore might
      help for guidance of disease progression in iPAH patients at V2.

PMID- 28516396
TI  - Body Sanctification and Sleep in Adolescents with Cystic Fibrosis: A Pilot Study.
AB  - Imbuing one's body with divine significance is associated with health-protective
      behaviors. The purpose of this study was to determine whether adolescents with a
      life-shortening, chronic disease (cystic fibrosis) who sanctified their bodies
      also received adequate sleep. Data from Daily Phone Diaries and questionnaire
      replies from 45 adolescents with cystic fibrosis (ages 11-19 years) were
      analyzed. A significant relationship between body sanctification and sleep was
      found, with between-gender differences. Body sanctification is an understudied
      construct which is associated with healthy behaviors.

PMID- 28516397
TI  - Perspective of Islamic Self: Rethinking Ibn al-Qayyim's Three-Heart Model from
      the Scope of Dynamical Social Psychology.
AB  - The present article proposes the perspective of Islamic self (PIS), which is
      guided by three core principles. First, the Islamic self is shaped by the God's
      predicament: The life test. Second, the structure of the self and its spiritual
      virtues represent means to succeed the life test. Third, the complex dynamics of
      the self can be mathematically formalized into a parsimonious framework.
      Specifically, the PIS considers the self as a dynamical system characterized by
      the emergence of self-organized stable and unstable patterns taking the form of
      positive ("illuminating heart") or negative ("darkened heart") dynamics.

PMID- 28516394
TI  - Linguistic asymmetry, egocentric anchoring, and sensory modality as factors for
      the observed association between time and space perception.
AB  - Temporal and spatial representations have been consistently shown to be
      inextricably intertwined. However, the exact nature of time-space mapping remains
      unknown. On the one hand, the conceptual metaphor theory postulates unilateral,
      asymmetric mapping of time onto space, that is, time is perceived in spatial
      terms but the perception of space is relatively independent of time. On the other
      hand, a theory of magnitude assumes bilateral and symmetric interactions between
      temporal and spatial perceptions. In the present paper, we argue that the
      concepts of linguistic asymmetry, egocentric anchoring, and sensory modality
      provide potential explanations for why evidences favoring both asymmetry and
      symmetry have been obtained. We first examine the asymmetry model and suggest
      that language plays a critical role in it. Next, we discuss the symmetry model in
      relation to egocentric anchoring and sensory modality. We conclude that since
      these three factors may jointly account for some conflicting past results
      regarding the strength and directionality of time-space mapping, they should be
      taken into serious consideration in future test designs.

PMID- 28516399
TI  - Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing
      cyclooxygenase-2 expression and chemotaxis of inflammatory cells.
AB  - PURPOSE: Radiation-induced oral mucositis is the most common side effect of
      radiotherapy in head and neck cancer; however, effective modalities for its
      prevention have not been established. In this study, we evaluated the
      effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for
      preventing radiation-induced mucositis and elucidated its effect on inflammatory
      responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2)
      expression, in an animal model. METHODS: Syrian hamsters, 8-9 weeks old, were
      enrolled in this study. Animals were irradiated with a single 40 Gy dose to the
      buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a
      normal diet daily. The therapeutic effect was determined based on the visual
      mucositis score, body weight, and histological examination of infiltrated
      neutrophils and COX2 expression. RESULTS: TJ-14 significantly reduced the
      severity of mucositis. The percentage with severe mucositis (score >=3) was 100%
      in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no
      difference in body weight change between the groups; however, weight gain in the
      untreated group tended to be suppressed compared to that in the TJ-14 group
      during the peak period of mucositis. In addition, TJ-14 inhibited the
      infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).
      CONCLUSIONS: TJ-14 reduced the severity of mucositis in an animal model by
      suppressing the inflammatory response. Because TJ-14 is inexpensive and its
      safety is established, it is a promising candidate for the standard treatment of
      radiation-induced mucositis in cancer patients.

PMID- 28516398
TI  - Gynecological brachytherapy for postoperative endometrial cancer: dosimetric
      analysis (Ir-192 vs Co-60).
AB  - INTRODUCTION: Endovaginal brachytherapy treatment dosimetry differences were
      studied using Ir-192 or Co-60 sources for postoperative endometrial cancer.
      MATERIALS AND METHODS: A prospective descriptive study was conducted. Thirty-six
      dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co
      60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose
      percentage at point 0 (applicator surface on the top of the cylinder) and dose
      percentage at point 1 (5 mm deep on the top of the cylinder). A comparative
      analysis was performed of the values obtained from each variable between Ir-192
      and Co-60 treatments. We compared average of each variables between Iridium and
      Cobalt by T Student for independent samples (SPSS 22). RESULTS: There were no
      significant differences on using Ir-192 or Co-60 by variables, except for dose
      percentage at point 1 in which we detected significant differences (Table 1).
      Table 1 The results Variables Sources Iridium 192 Cobalt 60 D2cc Rectum (mean
      dose) [rank] 6.01 Gy [3.99-7.90] 5.28 Gy [3.87-6,34] D2cc Bladder (mean dose)
      [rank] 5.82 Gy [4.20-8.38] 5.05 Gy [2.23-6.95] D2cc Sigmoid (mean dose) [rank]
      4.43 Gy [1.66-6.67] 2.33 Gy [0.60-4.28] Dose percentage at point 0a (mean) [rank]
      210.74% [120.90-234.90] 204.75% [177.10-223] Dose percentage at point 1b (mean)
      [rank] 93.49% [87.30-100.60] 100.11% [96.70-102] aPoint 0: point to the
      applicator surface bPoint 1: point to 5 mm applicator surface DISCUSSION:
      Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except
      dose percentage at point 1. In the scientific literature, some differences exist
      and there are some advantages in using cobalt.

PMID- 28516401
TI  - Endovascular Crossing of Chronic Total Occlusions Using an Impulse: An
      Explorative Design Study.
AB  - In this study we investigated whether exerting an impulse on a Chronic Total
      Occlusion (CTO) improves the success rate of CTO crossing as compared to the
      currently used method of statically pushing the guidewire against the CTO. A
      prototype (O2 mm) was developed that generates translational momentum using a
      spring-loaded indenter and converts it to an impulse during impact. Mechanical
      performance was evaluated by measuring the peak force and momentum for different
      spring compressions and strike distances in air and blood-mimicking fluid.
      Puncture performance, in terms of number of punctures, number of strikes to
      puncture, and energy transfer from the indenter to the CTO, was assessed for six
      tip shapes (stamp, wedge, spherical, pointed, hollow spherical, and ringed) on
      three CTO models with different weight percentages of gelatin and calcium. As a
      control, a O0.4 mm rigid rod was tested. A maximum indenter momentum of 1.3 mNs
      (velocity of 3.4 m/s), a peak force of 19.2 N (vs. 1.5 N reported in literature
      and 2.7 N for the control), and CTO displacement of 1.4 mm (vs. 2.7 mm for the
      control) were measured. The spherical and ringed tips were most effective, with
      on average 2.3 strikes to puncture the most calcified CTO model. The prototype
      generated sufficient peak forces to puncture highly calcified CTO models, which
      are considered most difficult to cross during PCI. Furthermore, CTO displacement
      was minimized, resulting in a more effective procedure. In future, a smaller,
      faster, and flexible clinical prototype will be developed.

PMID- 28516400
TI  - Systematic Investigation of the Role of Surfactant Composition and Choice of oil:
      Design of a Nanoemulsion-Based Adjuvant Inducing Concomitant Humoral and CD4+ T
      Cell Responses.
AB  - PURPOSE: Induction of cell-mediated immune (CMI) responses is crucial for vaccine
      mediated protection against difficult vaccine targets, e.g., Chlamydia
      trachomatis (Ct). Adjuvants are included in subunit vaccines to potentiate immune
      responses, but many marketed adjuvants stimulate predominantly humoral immune
      responses. Therefore, there is an unmet medical need for new adjuvants, which
      potentiate humoral and CMI responses. The purpose was to design an oil-in-water
      nanoemulsion adjuvant containing a synthetic CMI-inducing mycobacterial
      monomycoloyl glycerol (MMG) analogue to concomitantly induce humoral and CMI
      responses. METHODS: The influence of emulsion composition was analyzed using a
      systematic approach. Three factors were varied: i) saturation of the oil phase,
      ii) type and saturation of the applied surfactant mixture, and iii) surfactant
      mixture net charge. RESULTS: The emulsions were colloidally stable with a droplet
      diameter of 150-250 nm, and the zeta-potential correlated closely with the net
      charge of the surfactant mixture. Only cationic emulsions containing the
      unsaturated surfactant mixture induced concomitant humoral and CMI responses upon
      immunization of mice with a Ct antigen, and the responses were enhanced when
      squalene was applied as the oil phase. In contrast, emulsions with neutral and
      net negative zeta-potentials did not induce CMI responses. The saturation degree
      of the oil phase did not influence the adjuvanticity. CONCLUSION: Cationic, MMG
      analogue-containing nanoemulsions are potential adjuvants for vaccines against
      pathogens for which both humoral and CMI responses are needed.

PMID- 28516402
TI  - Effects of calcineurin inhibitors on sodium excretion in recipients of allogeneic
      hematopoietic stem cell transplantation.
AB  - Calcineurin inhibitors (CIs) such as cyclosporine A (CSA) and tacrolimus often
      cause renal dysfunction, resulting in increased serum creatinine, hyperkalemia,
      and hyperuricemia. However, the effects of CIs on sodium excretion have not been
      fully elucidated. We retrospectively evaluated the effects of CI administration
      on sodium excretion in recipients of allogeneic hematopoietic stem cell
      transplantation (HSCT). Fifty consecutive recipients each of allogeneic HSCT
      receiving either CSA or tacrolimus (100 patients in total) with available data
      for weekly fractional excretion of sodium (FENa) for a 4-week period after
      transplantation were enrolled in this retrospective analysis. No significant
      differences in patient characteristics were observed between CSA and tacrolimus
      groups except for the type of donor. FENa was significantly higher at the 3rd
      (1.25 +/- 0.80) and 4th weeks (1.53 +/- 1.06) after transplantation as compared
      with that at the 1st week (0.93 +/- 0.51; P < 0.01, P < 0.001, respectively) in
      the tacrolimus group, but not at any time point in the CSA group. In addition,
      FENa was significantly higher in the tacrolimus group than the CSA group at the
      4th week (1.53 +/- 1.06 vs. 1.13 +/- 0.80; P < 0.05). These results suggest that
      tacrolimus increases sodium excretion after allogeneic HSCT, and that this effect
      is minimal with CSA.

PMID- 28516404
TI  - Screening for Diabetic Eye Disease among Samoan Adults: A Pilot Study.
AB  - INTRODUCTION: The purpose of this study was to determine the prevalence of
      diabetic retinopathy in Samoa by piloting a retinal photography screening
      programme. METHODS: We performed a cross-sectional study of patients with
      diabetes who presented to the Tupua Tamasese Meaole eye clinic in Apia, Samoa,
      between May 2011 and September 2011. Study approval was granted by the National
      Health Service Board of Samoa, the Monash University Human Research Ethics
      Committee, and the study adhered to the Tenets of the Declaration of Helsinki.
      Following informed consent, data collection included patient demographics [age,
      area of residence (rural or urban)], type of diabetes, length of time since
      diagnosis, most recent random blood sugar and blood pressure levels. The subjects
      had three 45-degree retinal photographs taken in each eye with the Canon CR6-45NM
      camera. All gradable photographs were assessed for the presence of diabetic
      retinopathy or macular oedema using the International Clinical Diabetic
      Retinopathy Severity Scale and the International Clinical Diabetic Macular Oedema
      Severity scale, respectively. RESULTS: Two hundred and fourteen eyes from 107
      subjects were examined during the study period, all of whom had type 2 diabetes
      mellitus. Diabetic retinopathy was present in 53.3% (114/214) of eyes, with 14.5%
      having proliferative retinopathy and 7.5% with severe non-proliferative
      retinopathy. Also, 25.2% (54/214) had some evidence of macular oedema with 11.7%
      (25/214) requiring treatment. A statistically significant relationship existed
      between the length of time since diagnosis and the severity of both retinopathy
      (p < 0.001) and macular oedema (p = 0.031). Blood pressure more than 150/85 mmHg
      was associated with higher levels of diabetic retinopathy (p = 0.03) and macular
      oedema (p = 0.02). CONCLUSION: A comprehensive diabetic retinopathy screening
      programme is much needed in Samoa given the high prevalence of diabetic eye
      disease.

PMID- 28516403
TI  - Long-term clinical outcome of spinal Langerhans cell histiocytosis in children.
AB  - Spinal involvement of Langerhans cell histiocytosis (LCH) affects morbidity, but
      outcomes are not well understood. We analyzed long-term outcomes following
      uniform treatment at a single institution. Clinical characteristics and outcomes
      of spinal LCH patients were retrospectively analyzed. Height ratios were
      calculated using the anterior height of the involved vertebral body on magnetic
      resonance imaging (MRI) and the expected normal vertebral height. Twenty-two
      (22.4%) of 98 patients diagnosed with LCH had spinal involvement. The median age
      at diagnosis was 4.1 (range 0.6-12.3) years. Thirty-one spinal lesions were
      identified in 22 patients; the thoracic spine (n = 17) was most commonly
      affected. Eight lesions with minimal collapse, which appeared normal on plain
      radiography, were detected with MRI. All patients received vinblastine-based
      chemotherapy. Fourteen (70%) of 20 evaluable vertebral body collapses, including
      eight severe lesions, showed improvement in vertebral body height at a median
      follow-up of 6.0 (range 2.8-12.0) years. All traceable patients were alive
      without disease. Long-term follow-up of vertebral body collapse revealed
      vertebral height improvement in approximately 70% of spinal LCH patients, even in
      severe cases. MRI at diagnosis detected spinal lesions earlier with higher
      sensitivity than plain radiography.

PMID- 28516407
TI  - Components of sustainability considerations in management of petrochemical
      industries.
AB  - Sustainability comprises three pillars of social, environmental, and economic
      aspects. Petrochemical industry has a great inter-related complex impact on
      social and economic development of societies and adverse impact on almost all
      environmental aspects and resource depletion in many countries, which make
      sustainability a crucial issue for petrochemical industries. This study was
      conducted to propose components of sustainability considerations in management of
      petrochemical industries.A combination of exploratory study-to prepare a
      preliminary list of components of sustainable business in petrochemical
      industries based on review of literature and Delphi-to obtain experts' view on
      this preliminary list and provide a detailed list of components and sub
      components that should be addressed to bring sustainability to petrochemical
      industries, were used.Two sets of components were provided. First general
      components, which include stakeholders (staffs, society, and environment) with
      four sub-components, financial resources with 11 sub-components, improvement of
      design and processes with nine sub-components, policy and strategy of cleaner
      production with seven sub-components and leadership with seven sub-components.
      The second operational components included raw material supply and preparation
      with five, synthesis with ten, product separation and refinement with nine,
      product handling and storage with five, emission abatement with eight, and
      improvement of technology and equipment with 16 sub-components.

PMID- 28516406
TI  - Degradation and adsorption of tralkoxydim in Chinese soils and water-sediment
      environments.
AB  - Tralkoxydim is a cyclohexanedione herbicide primarily used for gramineous weed
      control in China. In this paper, we present results of a tralkoxydim laboratory
      environmental fate study characterizing its degradation, adsorption, and mobility
      behavior in three different soils and two water-sediment systems (river and lake)
      in China. Degradation half-life of tralkoxydim in soil under aerobic conditions
      was 5.1, 7.7, and 7.9 days in Jiangxi red soil, Taihu paddy soil, and Northeast
      China black soil, respectively. Under anaerobic and flooding conditions, half
      life values were 6.2, 15.1, and 19.8 days for the same three soils, respectively.
      Soil pH was the major factor effecting tralkoxydim degradation. In the aerobic
      water-sediment experiments, tralkoxydim degraded faster in the river system
      (total system half-life 43.3 days) than the lake system (total system half-life
      99.0 days). Correspondingly, its anaerobic degradation half-life values were 46.2
      and 53.3 days for the river and lake systems, respectively. Tralkoxydim
      adsorption in the three soils was found to follow the empirical Freundlich
      isotherm. The adsorption coefficient (K d ) was 8.60, 1.00, and 1.57 for Jiangxi
      red soil, Taihu paddy soil, and Northeast China black soil, respectively. Soil pH
      was the major factor effecting tralkoxydim adsorption. Adsorption free energy
      change was less than 40 kJ mol-1 in all three soils, indicating a physical
      mechanism in the process. Thin-layer chromatography (TLC) tests showed that
      relative to the solvent transport to 11.5 cm, the travel distance of tralkoxydim
      was 8-10 cm in the three soils, corresponding Rf values at 0.05, 0.35, and 0.75
      for Jiangxi red soil, Taihu paddy soil, and Northeast China black soil,
      respectively. Results of this work suggest that under alkaline conditions,
      tralkoxydim adsorption becomes smaller; thus, assessments on its mobility and
      potential groundwater impact should focus on these soil types.

PMID- 28516405
TI  - Characterization of dissolved organic matter in an urbanized estuary located in
      Northeastern Brazil.
AB  - The Sal River estuary, which is located in the state of Sergipe, Northeastern
      Brazil, stands out as an urban estuary, anthropogenically impacted by untreated
      and treated wastewater discharge. Synchronous fluorescence spectroscopy and
      measurement of dissolved organic carbon (DOC) were used for characterization of
      dissolved organic matter (DOM) in the estuarine water. Dissolved organic carbon
      concentrations ranged from 7.5 to 19.0 mg L-1 and, in general, the highest values
      were recorded during dry season. For both seasons (dry and rainy), DOC presented
      an inverse linear relationship with salinity, which indicates a conservative
      dilution of organic matter coming into the estuary. During rainy season,
      anthropogenic organic constituents and humic substances from land-based sources
      predominated in DOM composition, carried by river flow. Whereas during the dry
      season, it has been observed a significant increase of products generated by
      microbial degradation of anthropogenic organic matter. The relationships between
      fluorescence intensity and salinity suggest a conservative behavior during rainy
      season and a non-conservative behavior during dry season, with addition of
      fluorescent organic matter into the intermediate zone of the estuary.
      Photodegradation by action of sunlight caused a decrease in fluorescence
      intensity of humic and tryptophan-like constituents and the release of
      photoproducts, resulting in an increase in fluorescence intensity of protein-like
      constituents.

PMID- 28516408
TI  - The Poisoning Severity Score: If It Did Not Exist, We Would Have To Invent It.

PMID- 28516410
TI  - Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and
      Hepatoprotective and Toxicity Evaluation.
AB  - The objectives of this study were to formulate, characterize silymarin-loaded
      Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic
      effects after oral administration. SNPs were prepared by nanoprecipitation
      technique and were evaluated for particle size, entrapment efficiency, TEM, solid
      state characterization, and in vitro drug release. The hepatoprotective activity
      was evaluated after oral administration of selected SNPs in carbon tetrachloride
      intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed.
      The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w
      Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle
      size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after
      12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR
      studies suggested the presence of silymarin in an amorphous state and absence of
      chemical interaction. The hepatoprotective evaluation of the selected SNPs in
      CCl4-intoxicated rats revealed significant improvement in the activities of
      different biochemical parameters (P <= 0.01) compared to the marketed product.
      The histopathological studies suggested that the selected SNPs produced better
      hepatoprotective effect in CCl4-intoxicated rats compared with the commercially
      marketed product. Toxicity study revealed no evident toxic effect for blank or
      silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The
      obtained results suggested that the selected SNPs were safe and potentially
      offered enhancement in the pharmacological hepatoprotective properties of
      silymarin.

PMID- 28516409
TI  - Survival After Severe Rhabdomyolysis Following Monensin Ingestion.
AB  - INTRODUCTION: Monensin is a veterinary antibiotic with a narrow therapeutic
      window that has led to lethal intoxication in many animal species. Only two prior
      cases of human toxicity have been reported, both fatal. We present the first case
      of survival from severe toxicity following monensin ingestion. CASE: A 58-year
      old man presented with 8 days of vomiting and abdominal pain. Due to delusions of
      central nervous system toxoplasmosis, he ingested 300 mg of monensin. His
      laboratory studies revealed severe rhabdomyolysis without renal dysfunction.
      Total creatine kinase (CK) peaked above 100,000 U/L. His CK decreased to 5192 U/L
      after 15 days of aggressive hydration and sodium bicarbonate therapy. His
      ejection fraction on echocardiogram decreased from 69 to 56%. DISCUSSION: Reports
      on acute clinical effects after human exposure to monensin are limited. Ingestion
      is known to cause skeletal and cardiac muscle rhabdomyolysis and necrosis. Animal
      studies demonstrate that monensin's toxicity is due to increases in intracellular
      sodium concentrations and Ca2+ release. To date, no effective antidotal treatment
      has been described. CONCLUSIONS: Monensin is a veterinary medication not approved
      for human use by the US Food and Drug Administration. Though poorly studied in
      humans, this case demonstrates the severe harm that may occur following
      ingestion.

PMID- 28516411
TI  - Preparation of Essential Oil-Based Microemulsions for Improving the Solubility,
      pH Stability, Photostability, and Skin Permeation of Quercetin.
AB  - Quercetin can bring many benefits to skin based on its various bioactivities.
      However, the therapeutic effect of quercetin is limited due to the poor water
      solubility, pH instability, light instability, and skin permeation. The aim of
      the present work was applying essential oil-based microemulsions to improve the
      solubility, pH stability, photostability, and skin permeation of quercetin for
      topical application. Peppermint oil (PO-ME), clove oil (CO-ME), and rosemary oil
      (RMO-ME) were selected as model essential oils. Microemulsions composed of
      Cremophor EL/1,2-propanediol/essential oils (47:23:30, w/w) were selected as
      model formulations, based on the pseudo-ternary phase diagram and the
      characterizations. In the solubility study, the solubility of quercetin was
      improved dozens of times by microemulsions. Quercetin was found instable under
      alkaline condition, with 50% degraded in the solution of pH 13. However, PO-ME,
      CO-ME, and RMO-ME could protect quercetin from the hydroxide ions, with 47, 9,
      and 12% of quercetin degraded. In the photostability study, the essential oil
      based microemulsions showed the capability of protecting quercetin from
      degradation under UV radiation. Where more than 67% of quercetin was degraded in
      aqueous solution, while less than 7% of quercetin degraded in microemulsions. At
      last, the in vitro skin permeation study showed that the essential oil-based
      microemulsions could enhance the permeation capacity of quercetin by 2.5-3 times
      compared to the aqueous solution. Hence, the prepared essential oil
      microemulsions could improve the solubility, pH stability, photostability, and
      skin permeation of quercetin, which will be beneficial for its topical
      application.

PMID- 28516412
TI  - Optimization of Adhesive Pastes for Dental Caries Prevention.
AB  - Dental caries prevention products available on the market contain only
      remineralizing agents or antibacterial agents. This study aimed to develop
      adhesive pastes containing calcium phosphate and alpha-mangostin for dental
      caries prevention using the optimization technique. Calcium phosphate was used as
      a remineralizing agent, and extracted alpha-mangostin was used as an
      antibacterial agent. The effect of the independent variables, which were fumed
      silica, Eudragit(r) EPO, polyethylene glycol, and ethyl alcohol, on the responses
      was investigated. The drying time, erosion rate, calcium release rate, and alpha
      mangostin release rate were established as the measured responses. An equation
      and a model of the relationship were constructed. An optimal formulation was
      obtained, and its effect on dental caries prevention was investigated using the
      pH-cycling model. The quadratic equation revealed that the drying time, calcium
      release rate, and alpha-mangostin release rate tended to decrease when increasing
      the fumed silica and decreasing other factors. The erosion rate tended to
      increase when decreasing Eudragit(r) EPO and increasing other factors. The
      observed responses of the optimal adhesive pastes were not significantly
      different from the predicted responses. This result demonstrated that
      optimization is an efficient technique in the formulation development of the
      adhesive pastes. In addition, the optimal adhesive pastes could enhance acid
      resistance activity to the tooth enamel.

PMID- 28516413
TI  - Self-emulsification of Lipidic Drug Delivery System in Pure Water and in
      Concentrated Glycerol Solution.
AB  - Self-emulsifying drug delivery systems (SEDDS), often intended for oral delivery,
      are normally explored in biorelevant aqueous media. The high complexity of these
      multi-component systems leaves the understanding of self-emulsification poor,
      hindering formulation rationalization. In this work, we aimed to fill this gap by
      studying the effects of glycerol on the self-emulsification of a ternary
      component formulation made of 20% w/w Tween 80, 15% w/w Span 80, and 65% w/w
      Captex 300 Low C6. The behavior of SEDDS in pure water and a binary mixture of
      water and glycerol (58.8% w/w) were investigated by optical microscopy, SAXS
      (small angle X-ray scattering), dynamic light scattering, and surface tension
      measurements. The presence of glycerol, at 58.8% w/w, altered the self
      emulsification behavior by suppressing the formation of lamellar structures
      observed in the presence of water, reducing the droplet mean diameter from 0.2 to
      0.1 MUm and changing the mechanism of self-emulsification. As co-surfactant,
      glycerol may intercalate within the polyoxyethylene chains of the surfactant at
      the palisade layer, increasing the interface flexibility and expanding it. Since
      no free water is available at the investigated glycerol concentration, glycerol,
      which is also a co-solvent, may additionally modify long-range interactions by
      reducing Van-der-Waals attractions or giving rise to repulsive surface-solvent
      mediated forces of entropic origin. These effects could be exploited to
      rationalize SEDDS formulations, widening their use within the pharmaceutical
      industry.

PMID- 28516414
TI  - Optimized Mucoadhesive Coated Niosomes as a Sustained Oral Delivery System of
      Famotidine.
AB  - The objective of this study is to develop an oral formulation of famotidine
      niosomes coated with a mucoadhesive polymer, chitosan. Famotidine (FMT) has low
      oral bioavailability of 40-45% and short half-life between 2.5 to 4 h. Famotidine
      is classified as class IV in BCS because of its low aqueous solubility (0.1% w/v)
      and low permeability. Thus, FMT was loaded to the bioadhesive coated niosomes to
      improve its solubility, enhance its oral bioavailability, and sustain FMT release
      pattern. Different formulations were prepared by thin-film hydration method and
      characterized in terms of entrapment efficiency, morphological features, vesicle
      size, and zeta potential. In vitro release and ex vivo permeability of famotidine
      from the formulations were evaluated. The optimized formula was coated with
      chitosan and its mucoadhesion and stability in bile salt was tested. The
      optimized formula showed a high entrapment efficiency of 74%, as well sustained
      the in vitro release of FMT in the simulated gastric medium and enhanced its
      permeation through an excised goat's intestinal membrane by 1.4 fold in
      comparison to FMT control suspension. The mucoadhesive coated formula exhibited a
      significantly higher (p < 0.05) mucoadhesive efficiency and more stability in the
      bile salt as compared to the uncoated formula. Therefore, it could be considered
      as an efficient delivery system to maintain the prolonged release of FMT and
      improve its oral bioavailability.

PMID- 28516415
TI  - Signal Amplification Technologies for the Detection of Nucleic Acids: from Cell
      Free Analysis to Live-Cell Imaging.
AB  - Due to their unique properties, such as programmability, ligand-binding
      capability, and flexibility, nucleic acids can serve as analytes and/or
      recognition elements for biosensing. To improve the sensitivity of nucleic acid
      based biosensing and hence the detection of a few copies of target molecule,
      different modern amplification methodologies, namely target-and-signal-based
      amplification strategies, have already been developed. These recent signal
      amplification technologies, which are capable of amplifying the signal intensity
      without changing the targets' copy number, have resulted in fast, reliable, and
      sensitive methods for nucleic acid detection. Working in cell-free settings,
      researchers have been able to optimize a variety of complex and quantitative
      methods suitable for deploying in live-cell conditions. In this study, a
      comprehensive review of the signal amplification technologies for the detection
      of nucleic acids is provided. We classify the signal amplification methodologies
      into enzymatic and non-enzymatic strategies with a primary focus on the methods
      that enable us to shift away from in vitro detecting to in vivo imaging. Finally,
      the future challenges and limitations of detection for cellular conditions are
      discussed.

PMID- 28516416
TI  - Anaerobic Digestion of Sugarcane Vinasse Through a Methanogenic UASB Reactor
      Followed by a Packed Bed Reactor.
AB  - The anaerobic treatment of raw vinasse in a combined system consisting in two
      methanogenic reactors, up-flow anaerobic sludge blanket (UASB) + anaerobic packed
      bed reactors (APBR), was evaluated. The organic loading rate (OLR) was varied,
      and the best condition for the combined system was 12.5 kg COD m-3day-1 with
      averages of 0.289 m3 CH4 kg COD r-1for the UASB reactor and 4.4 kg COD m-3day-1
      with 0.207 m3 CH4 kg COD r-1 for APBR. The OLR played a major role in the
      emission of H2S conducting to relatively stable quality of biogas emitted from
      the APBR, with H2S concentrations <10 mg L-1. The importance of the sulphate to
      COD ratio was demonstrated as a result of the low biogas quality recorded at the
      lowest ratio. It was possible to develop a proper anaerobic digestion of raw
      vinasse through the combined system with COD removal efficiency of 86.7% and
      higher CH4 and a lower H2S content in biogas.

PMID- 28516417
TI  - Microbial Lipid Production from Enzymatic Hydrolysate of Pecan Nutshell
      Pretreated by Combined Pretreatment.
AB  - Biodiesel is a fuel composed of monoalkyl esters of long-chain fatty acids
      derived from renewable biomass sources. In this study, biomass waste pecan
      nutshell (PS) was attempted to be converted into microbial oil. For effective
      utilization of PS, sequential pretreatment with ethylene glycol-H2SO4-water
      (78:2:20, wt:wt:wt) at 130  degrees C for 30 min and aqueous ammonia (25 wt%) at
      50  degrees C for 24 h was used to enhance its enzymatic saccharification.
      Significant linear correlation was obtained about delignification
      saccharification (R 2 = 0.9507). SEM and FTIR results indicated that combination
      pretreatment could effectively remove lignin and xylan in PS for promoting its
      enzymatic saccharification. After 72 h, the reducing sugars from the hydrolysis
      of 50 g/L pretreated PS by combination pretreatment could be obtained at 73.6%
      yield. Using the recovered PS hydrolysates containing 20 g/L glucose as carbon
      source, microbial lipids produced from the PS hydrolysates by Rhodococcus opacus
      ACCC41043. Four fatty acids including palmitic acid (C16:0; 23.1%), palmitoleic
      acid (C16:1; 22.4%), stearic acid (C18:0; 15.3%), and oleic acid (C18:1; 23.9%)
      were distributed in total fatty acids. In conclusion, this strategy has potential
      application in the future.

PMID- 28516418
TI  - Improvement of the Stabilization and Activity of Protocatechuate 3,4-Dioxygenase
      Isolated from Rhizobium sp. LMB-1 and Immobilized on Fe3O4 Nanoparticles.
AB  - Protocatechuate 3,4-dioxygenase (P34O), which is isolated from Rhizobium sp. LMB
      1, catalyzes the ring cleavage step in the metabolism of aromatic compounds, and
      has great potential for environmental bioremediation. However, its structure is
      very sensitive to different environmental factors, which weaken its activity.
      Immobilization of the enzyme can improve its stability, allow reusability, and
      reduce operation costs. In this work, the relative molecular mass of the native
      P34O enzyme was determined to be 500 kDa by gel filtration chromatography on
      Sephadex G-200, and the enzyme was immobilized onto (3-aminopropyl)
      triethoxysilane-modified Fe3O4 nanoparticles (NPs) by the glutaraldehyde method.
      The optimum pH of immobilized and free P34O was unaffected, but the optimum
      temperature of immobilized P34O increased from 60 to 70  degrees C, and the
      thermal stability of immobilized P34O was better than that of the free enzyme and
      showed higher enzymatic activity at 60 and 70  degrees C. In addition, with the
      exception of Fe3+, most metal ions and organic chemicals could not improve the
      activity of free and immobilized P34O. The kinetic parameters of the immobilized
      P34O were higher than those of the free enzyme, and immobilized P34O on Fe3O4 NPs
      could be reused ten times without a remarkable decrease in enzymatic activity.

PMID- 28516420
TI  - Event models and the fan effect.
AB  - The current study explored the persistence of event model organizations and how
      this influences the experience of interference during retrieval. People in this
      study memorized lists of sentences about objects in locations, such as "The
      potted palm is in the hotel." Previous work has shown that such information can
      either be stored in separate event models, thereby producing retrieval
      interference, or integrated into common event models, thereby eliminating
      retrieval interference. Unlike prior studies, the current work explored the
      impact of forgetting up to 2 weeks later on this pattern of performance. We
      explored three possible outcomes across the various retention intervals. First,
      consistent with research showing that longer delays reduce proactive and
      retroactive interference, any retrieval interference effects of competing event
      models could be reduced over time. Second, the binding of information into events
      models may weaken over time, causing interference effects to emerge when they had
      previously been absent. Third, and finally, the organization of information into
      event models could remain stable over long periods of time. The results reported
      here are most consistent with the last outcome. While there were some minor
      variations across the various retention intervals, the basic pattern of event
      model organization remained preserved over the two-week retention period.

PMID- 28516422
TI  - A Mixed Methods Study of Barriers to Formal Diagnosis of Autism Spectrum Disorder
      in Adults.
AB  - Delayed diagnosis of autism spectrum disorder (ASD) into adulthood is common, and
      self-diagnosis is a growing phenomenon. This mixed methods study aimed to explore
      barriers to formal diagnosis of ASD in adults. In a qualitative strand, secondary
      analysis of data on the experiences of 114 individuals who were self-diagnosed or
      formally diagnosed with ASD in adulthood was used to identify barriers. In a
      quantitative strand, 665 individuals who were self-diagnosed or formally
      diagnosed in adulthood were surveyed online to examine incidence and severity of
      barriers. Fear of not being believed by professionals was identified as the most
      frequently occurring and most severe barrier. Professionals must strategize to
      build trust with individuals with ASD, particularly when examining the accuracy
      of self-diagnosis.

PMID- 28516421
TI  - Differential Fairness Decisions and Brain Responses After Expressed Emotions of
      Others in Boys with Autism Spectrum Disorders.
AB  - Little is known about how emotions expressed by others influence social decisions
      and associated brain responses in autism spectrum disorders (ASD). We
      investigated the neural mechanisms underlying fairness decisions in response to
      explicitly expressed emotions of others in boys with ASD and typically developing
      (TD) boys. Participants with ASD adjusted their allocation behavior in response
      to the emotions but reacted less unfair than TD controls in response to
      happiness. We also found reduced brain responses in the precental gyrus in the
      ASD versus TD group when receiving happy versus angry reactions and autistic
      traits were positively associated with activity in the postcentral gyrus. These
      results provide indications for a role of precentral and postcentral gyrus in
      social-affective difficulties in ASD.

PMID- 28516424
TI  - Differing Developmental Trajectories in Heart Rate Responses to Speech Stimuli in
      Infants at High and Low Risk for Autism Spectrum Disorder.
AB  - We investigated heart rate (HR) in infants at 3, 6, 9, and 12 months of age, at
      high (HRA) and low (LRC) familial risk for ASD, to identify potential
      endophenotypes of ASD risk related to attentional responses. HR was extracted
      from functional near-infrared spectroscopy recordings while infants listened to
      speech stimuli. Longitudinal analysis revealed that HRA infants and males
      generally had lower baseline HR than LRC infants and females. HRA infants showed
      decreased HR responses to early trials over development, while LRC infants showed
      increased responses. These findings suggest altered developmental trajectories in
      physiological responses to speech stimuli over the first year of life, with HRA
      infants showing less social orienting over time.

PMID- 28516423
TI  - Exploring the Components of Advanced Theory of Mind in Autism Spectrum Disorder.
AB  - Performance of a group of 35 youth and adults with High-Functioning Autism (HFA)
      was compared with a typical developing (TD) group on three Advanced Theory of
      Mind tests. The distinction between the social-cognitive and social-perceptual
      components of Theory of Mind was also explored. The HFA group had more
      difficulties in all tasks. Performance on the two social-cognitive tests was
      highly correlated in the HFA group, but these were not related with the social
      perceptual component. These results suggest that the youth with HFA have
      difficulties on all the components of social knowledge but may be using different
      underlying cognitive abilities depending on the nature of the task.

PMID- 28516425
TI  - A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X
      Syndrome.
AB  - We examined the reliability, validity and factor structure of the Eye Contact
      Avoidance Scale (ECAS), a new 15-item screening tool designed to measure eye
      contact avoidance in individuals with fragile X syndrome (FXS). Internal
      consistency of the scale was acceptable to excellent and convergent validity with
      the Social Responsiveness Scale, Second Edition (SRS-2) and the Anxiety,
      Depression, and Mood Scale (ADAMS) was good. Boys with a comorbid ASD diagnosis
      obtained significantly higher scores on the ECAS compared to boys without ASD,
      when controlling for communication ability. A confirmatory factor analysis
      indicated that a two-factor model (avoidance and aversion) provided an excellent
      fit to the data. The ECAS appears to be a promising reliable and valid tool that
      could be employed as an outcome measure in future pharmacological/behavioral
      treatment trials for FXS.

PMID- 28516427
TI  - The organism strikes back: Chlorella algae and their impact on photosynthesis
      research, 1920s-1960s.
AB  - Historians and philosophers of twentieth-century life sciences have demonstrated
      that the choice of experimental organism can profoundly influence research
      fields, in ways that sometimes undermined the scientists' original intentions.
      The present paper aims to enrich and broaden the scope of this literature by
      analysing the career of unicellular green algae of the genus Chlorella. They were
      introduced for the study of photosynthesis in 1919 by the German cell
      physiologist Otto H. Warburg, and they became the favourite research objects in
      this field up to the 1960s. The paper argues that dealing with Chlorella's high
      metabolic flexibility was crucial for the emergence of a new conception of
      photosynthesis, as a plastic, integrated system of pathways. At the same time, it
      led to new collaborations between physiologists and phycologists, both of whom
      started to re-orient their studies in ecologically informed directions. Following
      Chlorella's trail, hence, not only elucidates how experimental organisms forced
      scientists to change their conceptual approaches and techniques, but also
      provides insight into the interaction of different lines of research of mid
      twentieth century plant sciences.

PMID- 28516428
TI  - Cerebrovascular Angiogenic Reprogramming upon LRP1 Repression: Impact on
      Sphingosine-1-Phosphate-Mediated Signaling in Brain Endothelial Cell
      Chemotactism.
AB  - Switches in sphingolipid metabolism have recently been associated with oncogenic
      transformation, and a role for the low-density lipoprotein receptor-related
      protein 1 (LRP1) in sphingosine-1-phosphate (S1P) proangiogenic signaling
      inferred. S1P signaling crosstalk with LRP1 in brain microvascular endothelial
      cells (HBMEC) is however unclear. Transient in vitro siLRP1 gene silencing was
      compared to stable shLRP1 knockdown. We observed decreased expression of
      CCAAT/enhancer binding protein beta (C/EBPbeta), a transcription factor for which
      multiple binding sites are found within the promoter sequences of all five S1P
      receptor members, upon stable but not transient LRP1 repression. Chemotactic
      migration of brain EC isolated from Lrp1(EC)-/- mice and of stable shLRP1 HBMEC
      became unresponsive to S1P, partly due to altered ERK and p38 MAPK pathways,
      whereas chemotactism remained unaltered following transient in vitro siLRP1
      repression. Diminished S1P1, S1P3, and S1P5 expression were observed in stable
      shLRP1 HBMEC and in brain EC isolated from Lrp1(EC)-/- mice. Overexpression of
      LRP1 cluster IV rescued S1P-mediated cell migration through increased S1P3
      transcription in shLRP1 HBMEC. Our study highlights an adaptive signaling
      crosstalk between LRP1 and specific S1P receptors which may regulate the
      angiogenic response of brain EC and be targeted at the blood-brain barrier in
      future therapeutic strategies.

PMID- 28516426
TI  - Characterization of Medication Use in a Multicenter Sample of Pediatric
      Inpatients with Autism Spectrum Disorder.
AB  - Nearly 11% of youth with Autism Spectrum Disorder (ASD) undergo psychiatric
      hospitalization, and 65% are treated with psychotropic medication. Here we
      characterize psychotropic medication usage in subjects enrolled in the Autism
      Inpatient Collection. Participant psychotropic medication usage rates topped 90%
      at admission and discharge, though there was a decline at 2-month follow-up.
      Antipsychotics, ADHD medications, and sleep aids were the most commonly reported
      classes of medications. The impact of age, gender, and non-verbal IQ on
      medication usage rates was minimal, though age and IQ may play a role in
      prescribing practices. Future work is indicated to explore medication usage
      trends, the impact of clinical factors on medication use rates, and the safety of
      psychotropic medications in youth with ASD.

PMID- 28516419
TI  - Abstracts of the 52nd Workshop for Pediatric Research : Frankfurt, Germany. 27-28
      October 2016.

PMID- 28516429
TI  - Cardinal Epigenetic Role of non-coding Regulatory RNAs in Circadian Rhythm.
AB  - Circadian rhythm which governs basic physiological activities like sleeping,
      feeding and energy consumption is regulated by light-controlled central clock
      genes in the pacemaker neuron. The timekeeping machinery with unique
      transcriptional and post-transcriptional feedback loops is controlled by
      different small regulatory RNAs in the brain. Roles of the multiple neuronal
      genes, especially post-transcriptional regulation, splicing, polyadenylation,
      mature mRNA editing, and stability of translation products, are controlled by
      epigenetic activities orchestrated via small RNAs. Collectively, these mechanisms
      regulate clock and light-controlled genes for effecting pacemaker activity and
      entrainment. Regulatory small RNAs of the circadian circuit, timekeeping
      mechanism, synchronization of regular entrainment, oscillation, and rhythmicity
      are regulated by diversified RNA molecules. Regulatory small RNAs operate
      critical roles in brain activities including the neuronal clock activity. In this
      report, we propose the emergence of the earlier unexpected small RNAs for a
      historic perspective of epigenetic regulation of the brain clock system.

PMID- 28516430
TI  - Ramelteon Improves Post-traumatic Stress Disorder-Like Behaviors Exhibited by
      Fatty Acid-Binding Protein 3 Null Mice.
AB  - We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3 
      /-) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2
      receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null
      mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction,
      and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably,
      chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor
      agonist, improved all PTSD-like behaviors tested in Fabp3 -/- mice. Relevant to
      mechanisms underlying impaired fear extinction, we observed significantly reduced
      levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      autophosphorylation without changes in ERK phosphorylation in the anterior
      cingulate cortex (ACC). Inversely, CaMKII autophosphorylation increased in the
      basolateral amygdala (BLA) but remained relatively unchanged in hippocampus of
      Fabp3 -/- mice. Likewise, the number of c-Fos-positive neurons in BLA
      significantly increased after exposure to contextual fear conditions but remained
      unchanged in the central nucleus of the amygdala (CeA). Importantly, chronic
      ramelteon administration (1.0 mg/kg, p.o.) restored abnormal c-Fos expression and
      CaMKII autophosphorylation in the ACC and BLA of Fabp3 -/- mice. Finally, the
      melatonin receptor antagonist luzindole (2.5 mg/kg, i.p.) blocked ramelteon
      dependent improvements. Taken together, Fabp3 -/- mice show PTSD-like behaviors,
      and ramelteon is a likely attractive candidate for PTSD therapy.

PMID- 28516432
TI  - Measurement of piperacillin plasma concentrations in cancer patients with
      suspected infection.
AB  - BACKGROUND: Piperacillin (PIP) in combination with tazobactam is commonly used
      for anti-infective treatment in cancer patients. PIP exerts a time-dependent
      killing. Thus, the maintenance of plasma concentrations above a pre-defined
      target concentration for a pre-defined time may be relevant for optimal efficacy.
      It is assumed that PIP-plasma concentrations above the clinical breakpoint of the
      target pathogen [Pseudomonas aeruginosa, clinical breakpoint at minimal
      inhibitory concentration (MIC) 16 mg/L] should be reached for 100% of the dosing
      interval or >4xMIC (64 mg/L) for 50% of the dosing interval. Whereas studies in
      the intensive-care setting have shown underdosing in patients with sepsis, little
      is known about PIP-plasma concentrations in cancer patients. METHODS: Data of 56
      cancer patients who received piperacillin/tazobactam (PIP/TAZ, 4.5 g three times
      daily) as empiric therapy for suspected infection were analysed at baseline and 4
      h after the infusion. RESULTS: Median trough concentrations in steady state
      [median 3 days (IQR 3-5) after start of PIP/TAZ] were 4.6 mg/L (95% CI 0.3-136.3)
      and median PIP-plasma concentrations 4 h after infusion were 46.2 mg/L (95% CI
      10.1-285.6). A second evaluation 5 days (IQR 4-7) after start of PIP/TAZ
      confirmed these results: trough concentrations were 2.7 mg/L (95% CI 0.5-6.3),
      concentrations after 4 h 28.0 mg/L (95% CI 1.7-47.3). A good renal function was
      associated with lower plasma concentrations (r = -0.388, p < 0.003). Detailed
      pharmacokinetic measurements in six patients showed low maximum plasma
      concentration (median 165 mg/L) and a rapid decline of plasma concentrations
      (median plasma half time 1.38 h). CONCLUSION: In conclusion, piperacillin plasma
      concentrations in cancer patients are below target levels warranting prospective
      trials to investigate therapeutic drug monitoring.

PMID- 28516433
TI  - With Decades of Perspective, Craig Henderson Observes That Treatment of Breast
      Cancer Has Come a Long Way.

PMID- 28516434
TI  - Gross Hematuria and Suspicious Bladder Lesions in a 52-Year-Old North African
      Immigrant.

PMID- 28516435
TI  - Management Considerations in Cancer Patients With Rheumatoid Arthritis.
AB  - Rheumatoid arthritis is a common inflammatory disease that requires treatment
      with immunosuppressants to control symptoms and avoid joint destruction. Managing
      cancer in patients with concomitant rheumatoid arthritis poses special challenges
      that require close coordination of care between oncologists and rheumatologists.
      Potential clinical issues needing special consideration include: 1) perioperative
      management in patients undergoing cancer surgery, which often requires
      discontinuation of antirrheumatic therapy; 2) use of immunosuppressant therapies
      for rheumatoid arthritis, especially biologic agents that inhibit cytokine and
      immune pathways, which conceivably could affect immune-mediated antitumor
      responses (the issues are different in patients with active cancer vs those with
      a past history of cancer and no recurrences); 3) management in the palliative
      care setting; and 4) use of cancer immunotherapy, such as checkpoint inhibitor
      agents, in patients with pre-existing rheumatoid arthritis. We explore these
      clinical issues in case-based scenarios. In all cases, clinical decision making
      must include a careful weighing of risks and benefits of both cancer treatments
      and antirrheumatic therapies, with attention given to prognosis and life
      expectancy, quality of life, and patient preferences.

PMID- 28516436
TI  - The Growing Challenge of Young Adults With Colorectal Cancer.
AB  - Although the incidence of colorectal cancer is declining in the overall US
      population, the rates of colorectal cancer are rising among adolescent and young
      adult (AYA) patients-defined as individuals under 45 years of age. This
      population includes patients deemed too young for routine colorectal cancer
      screening, which in the United States is typically initiated at age 50 for men
      and women at average risk. Clinicopathologic differences have long been observed
      between AYAs and older patients with colorectal cancer. In addition, recently
      available high-throughput DNA sequencing techniques have revealed different rates
      of genetic alterations between these two groups, indicating potential molecular
      differences in the disease state and suggesting the need for alternative
      treatment strategies in younger patients. AYA patients with colorectal cancer
      often receive more aggressive treatment regimens than their older counterparts,
      without a corresponding improvement in survival. Furthermore, these younger
      patients have particular survivorship issues that warrant attention from the
      oncology community. In this review, we address specific issues pertaining to AYA
      patients with colorectal cancer, including evaluation for hereditary colorectal
      cancer syndromes, clinicopathologic and biologic features unique to AYA patients
      with colorectal cancer, treatment outcomes, and survivorship.

PMID- 28516437
TI  - Point/Counterpoint: Is Lymphadenectomy Required in Endometrial Cancer for
      Adequate Surgical Staging?

PMID- 28516438
TI  - Point/Counterpoint: Is Lymphadenectomy Required in Endometrial Cancer for
      Adequate Surgical Staging?

PMID- 28516439
TI  - Reassessment of Anti-CD20 Therapy in Lymphoid Malignancies: Impact, Limitations,
      and New Directions.
AB  - The addition of anti-CD20 monoclonal antibodies to the treatment of B-cell
      malignancies has dramatically affected the field as well as the lives of
      patients. Rituximab in particular has been combined safely with conventional
      chemotherapy and has resulted in improved overall survival in major histologic
      subtypes of B-cell lymphoma and chronic lymphocytic leukemia. It is incorporated
      into the standard initial treatment of nearly all of these diseases. Novel anti
      CD20 antibodies are currently under development. Two of these agents, ofatumumab
      and obinutuzumab, have been approved for use in certain clinical settings.
      Research comparing these newer antibodies with rituximab is ongoing. As these
      newer antibodies are further studied and developed, improvements in response and
      progression-free survival need to be considered in the context of clinical
      benefit as well as toxicity, especially in indolent diseases. Research involving
      rituximab biosimilars is ongoing as well, and recent preliminary data demonstrate
      similar efficacy and tolerability when compared with rituximab. An additional
      focus of ongoing research is the use of extended schedules of anti-CD20
      monoclonal antibodies, as the optimal duration of therapy remains ill-defined in
      many histologic subtypes. To maximize the use of these agents, well-validated
      clinical trial endpoints will need to be carefully considered.

PMID- 28516440
TI  - The Uncertainties of Rituximab and Related Therapies, 20 Years After Approval.

PMID- 28516441
TI  - Decision Making in the Surgical Management of Invasive Breast Cancer-Part 2:
      Expanded Applications for Breast-Conserving Surgery.
AB  - Treatment of early-stage invasive breast cancer with breast-conserving surgery
      plus radiation therapy (RT) yields overall survival outcomes equivalent to those
      achieved with mastectomy. Further, breast-conserving surgery is endorsed by the
      National Comprehensive Cancer Network as being supported by the highest-level,
      category 1 evidence. Advances in pathologic evaluation, management of multiple
      tumors, oncoplastic lumpectomy techniques, neoadjuvant chemotherapy, and
      hypofractionated RT can expand the pool of patients eligible for breast
      conserving surgery. Selected patients (for example, patients older than 70 years
      of age with hormone receptor-positive T1 tumors who are willing to commit to
      receiving adjuvant endocrine therapy) may be able to forgo RT completely. This
      article will detail current management approaches to achieving breast
      conservation in patients with invasive breast cancer, including cases of bulky
      tumors and/or multiple tumors.

PMID- 28516431
TI  - A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major
      Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a
      Common Cause?
AB  - There is copious evidence of abnormalities in resting-state functional network
      connectivity states, grey and white matter pathology and impaired cerebral
      perfusion in patients afforded a diagnosis of multiple sclerosis, major
      depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis).
      Systemic inflammation may well be a major element explaining such findings. Inter
      patient and inter-illness variations in neuroimaging findings may arise at least
      in part from regional genetic, epigenetic and environmental variations in the
      functions of microglia and astrocytes. Regional differences in neuronal
      resistance to oxidative and inflammatory insults and in the performance of
      antioxidant defences in the central nervous system may also play a role.
      Importantly, replicated experimental findings suggest that the use of high
      resolution SPECT imaging may have the capacity to differentiate patients afforded
      a diagnosis of CFS from those with a diagnosis of depression. Further research
      involving this form of neuroimaging appears warranted in an attempt to overcome
      the problem of aetiologically heterogeneous cohorts which probably explain
      conflicting findings produced by investigative teams active in this field.
      However, the ionising radiation and relative lack of sensitivity involved
      probably preclude its use as a routine diagnostic tool.

PMID- 28516442
TI  - Vaccines for the common cold.
AB  - BACKGROUND: The common cold is a spontaneously remitting infection of the upper
      respiratory tract, characterised by a runny nose, nasal congestion, sneezing,
      cough, malaise, sore throat, and fever (usually < 37.8o C). The widespread
      morbidity caused by the common cold worldwide is related to its ubiquitousness
      rather than its severity. The development of vaccines for the common cold has
      been difficult because of antigenic variability of the common cold virus and the
      indistinguishable multiple other viruses and even bacteria acting as infective
      agents. There is uncertainty regarding the efficacy and safety of interventions
      for preventing the common cold in healthy people. This is an update of a Cochrane
      review first published in 2011 and previously updated in 2013. OBJECTIVES: To
      assess the clinical effectiveness and safety of vaccines for preventing the
      common cold in healthy people. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to
      September 2016), Embase (1974 to September 2016), CINAHL (1981 to September
      2016), and LILACS (1982 to September 2016). We also searched three trials
      registers for ongoing studies and four websites for additional trials (February
      2017). We included no language or date restrictions. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of any virus vaccines compared with placebo
      to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two
      review authors independently evaluated methodological quality and extracted trial
      data. We resolved disagreements by discussion or by consulting a third review
      author. MAIN RESULTS: We found no additional RCTs for inclusion in this update.
      This review includes one RCT dating from the 1960s with an overall high risk of
      bias. The RCT included 2307 healthy participants, all of whom were included in
      analyses. This trial compared the effect of an adenovirus vaccine against
      placebo. No statistically significant difference in common cold incidence was
      found: there were 13 (1.14%) events in 1139 participants in the vaccines group
      and 14 (1.19%) events in 1168 participants in the placebo group (risk ratio 0.95,
      95% confidence interval 0.45 to 2.02; P = 0.90). No adverse events related to the
      live vaccine were reported. The quality of the evidence was low due to
      limitations in methodological quality and a wide 95% confidence interval.
      AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with low
      quality evidence. We found no conclusive results to support the use of vaccines
      for preventing the common cold in healthy people compared with placebo. We
      identified a need for well-designed, adequately powered RCTs to investigate
      vaccines for the common cold in healthy people. Any future trials on medical
      treatments for preventing the common cold should assess a variety of virus
      vaccines for this condition. Outcome measures should include common cold
      incidence, vaccine safety, and mortality related to the vaccine.

PMID- 28516443
TI  - Multiple red blood cell transfusions and iron overload in very low birthweight
      infants.
AB  - BACKGROUND AND OBJECTIVES: To estimate the risk of iron overload in very low
      birthweight (VLBW) infants who receive more than two red blood cell (RBC)
      transfusions, in comparison with those who receive two or less during their
      hospital stay. MATERIALS AND METHODS: Prospective open cohort study in VLBW
      infants with >2 (exposed) and <=2 (non-exposed) RBC transfusions. Ferritin,
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured
      at birth and after each RBC transfusion. The incidence of iron overload was
      determined. Risk factors were analysed using a logistic regression model. RBC
      transfusion volume correlations with ferritin, ALT and AST were calculated with
      Spearman's rank correlation coefficient, as well as correlations between ferritin
      and aminotransferases. RESULTS: A total of 63 patients were enrolled, 18 of which
      were exposed and 45 non-exposed. Twelve patients developed severe iron overload,
      eight exposed (44.5%) vs. four (8.8%) non-exposed (RR: 5, 95% CI: 1.7-14.6).
      Multivariate analysis showed that the number of transfusions increased the risk
      of iron overload (OR: 2.07, 95% CI: 1.36-2.14) while a higher one-minute Apgar
      score was associated with a lower risk (OR: 0.56, 95% CI: 0.32-0.99). Severe iron
      overload mainly occurred with a transfusion volume higher than 120 ml/kg. There
      was a positive correlation between ferritin and transfusion (r = 0.53; P <
      0.001). CONCLUSION: There was a higher risk of iron overload in exposed infants
      in comparison with non-exposed infants. Severe iron overload in VLBW infants may
      occur with a total transfusion volume >120 ml/kg.

PMID- 28516444
TI  - Toxicological Analysis of Opiates from Alternative Matrices Collected from an
      Exhumed Body.
AB  - In this case study, the body of a 45-year-old man was exhumed after 1 year at the
      request of the public prosecutor to assess whether the death was caused by drug
      consumption. Toxicological analyses were performed on several matrices, including
      liver, kidney, and the alternative matrices hair and teeth. The systematic
      toxicological analysis (STA), which consisted of basic and acid liquid/liquid
      extraction and gas chromatography-mass spectrometry (GC-MS) analysis, showed the
      presence of opiates in each of the matrices analyzed. Subsequently, to confirm
      and quantify the presence of opioids, samples of each of the matrices were
      subjected to solid-phase extraction and specific GC-MS analysis. The case
      presented demonstrates the possibility of drug detection in an exhumed body that
      has been buried for 1 year, despite the problems of quantitative interpretation
      of the data, and that toxicological results could be useful along with other
      forensic evidence.

PMID- 28516447
TI  - Metacarpophalangeal joint injury patterns on magnetic resonance imaging: A
      comparison in racing Standardbreds and Thoroughbreds.
AB  - The metacarpal condyle has received extensive attention as a predominant site of
      overload arthropathy in racehorses. However, detailed descriptions of MRI lesion
      patterns for the metacarpophalangeal joint and comparisons between types of
      racing horses are currently lacking. Aims of this retrospective, cross-sectional
      study were to describe and compare standing low-field magnetic resonance findings
      in the metacarpophalangeal joints for groups of Standardbreds and Thoroughbreds
      using systematic semiquantitative scores. Data archives at the Clinique
      Veterinaire Equine de Chantilly and Imavet were searched during the period from
      June 2010 to February 2016. Images were retrieved and reviewed by one reader. A
      total of 30 Standardbreds and 77 Thoroughbreds were sampled. The Thoroughbreds
      developed a much higher rate of stress fractures (40.3% vs. 10%) and overall more
      severe scores of subchondral sclerosis and bone marrow lesions than
      Standardbreds. The Standardbreds had more sites of subchondral bone defect and
      resorption, as well as higher synovitis and joint capsule thickening scores. Both
      Standardbreds and Thoroughbreds frequently developed multifocal subchondral
      lesions not limited to the distal palmar condyle. The Standardbreds had a higher
      tendency to develop dorsomedial joint pole subchondral injuries. Both
      Standardbreds and Thoroughbreds developed a noticeably high rate of periarticular
      soft tissue injuries (36.7% in Standardbreds and 20.8% in Thoroughbreds), which
      were rarely considered as the main contributors to the lameness. Findings
      supported the use of low-field MRI as a whole-organ assessment tool for
      Standardbreds and Thoroughbreds with suspected metacarpophalangeal joint
      injuries.

PMID- 28516445
TI  - Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish
      model.
AB  - The endocannabinoid system (eCBs), named after the plant Cannabis sativa,
      comprises cannabinoid receptors, endogenous ligands known as "endocannabinoids",
      and enzymes involved in the biosynthesis and degradation of these ligands, as
      well as putative transporters for these ligands. ECBs proteins and small
      molecules have been detected in early embryonic stages of many vertebrate models.
      As a result, cannabinoid receptors and endogenous as well as exogenous
      cannabinoids influence development and behavior in many vertebrate species.
      Understanding the precise mechanisms of action for the eCBs will provide an
      invaluable guide towards elucidation of vertebrate development and will also help
      delineate how developmental exposure to marijuana might impact health and
      cognitive/executive functioning in adulthood. Here we review the developmental
      roles of the eCBs in vertebrates, focusing our attention on the zebrafish model.
      Since little is known regarding the eCBs in zebrafish, we provide new data on the
      expression profiles of eCBs genes during development and in adult tissue types of
      this model organism. We also highlight exciting areas for future investigations,
      including the synaptic regulation of eCBs, its role in reward and addiction, and
      in nervous system development and plasticity.

PMID- 28516446
TI  - Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for
      Assessment of Therapeutics.
AB  - Pulmonary thrombosis is a significant cause of patient mortality; however, there
      are no effective in vitro models of thrombi formation in human lung microvessels
      that could also assess therapeutics and toxicology of antithrombotic drugs. Here,
      we show that a microfluidic lung alveolus-on-a-chip lined by human primary
      alveolar epithelium interfaced with endothelium and cultured under flowing whole
      blood can be used to perform quantitative analysis of organ-level contributions
      to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo
      responses, including platelet-endothelial dynamics and revealed that
      lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis
      by activating the alveolar epithelium, rather than acting directly on
      endothelium. This model is also used to analyze inhibition of endothelial
      activation and thrombosis due to a protease activated receptor-1 (PAR-1)
      antagonist, demonstrating its ability to dissect complex responses and identify
      antithrombotic therapeutics. Thus, this methodology offers a new approach to
      study human pathophysiology of pulmonary thrombosis and advance drug development.

PMID- 28516448
TI  - Management and outcome of clinically evident neck recurrence in patients with
      papillary thyroid cancer.
AB  - BACKGROUND: The aim of this study was to report our incidence of clinically
      evident neck recurrence, salvage neck management and subsequent outcomes in
      patients with papillary thyroid cancer. This is important to know so that
      patients with thyroid cancer can be properly counselled about the implications of
      recurrent disease and subsequent outcome. METHODS: An institutional database of
      3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed.
      Patients with nonpapillary histology and gross residual disease and those with
      distant metastases at presentation or distant metastases prior to nodal
      recurrence were excluded from the study. Of these, 99 (3.0%) patients developed
      clinically evident nodal recurrence. Details of recurrence and subsequent therapy
      were recorded for each patient. Subsequent disease-specific survival (sDSS),
      distant recurrence-free survival (sDRFS) and nodal recurrence-free survival
      (sNRFS) were determined from the date of first nodal recurrence using the Kaplan
      Meier method. RESULTS: Of the 99 patients, 59% were female and 41% male. The
      median age was 41 years (range 5-91). The majority of patients had pT3/4 primary
      tumours (63%) and were pN+ (78%) at initial presentation. The median time to
      clinically evident nodal recurrence was 28 months (range: 3-264). Nodal
      recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74
      (75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year
      sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were
      89.2% and 93.7%, respectively. CONCLUSION: In our series, isolated clinically
      evident nodal recurrence occurred in 3.0% of patients. Such patients are
      successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5
      years.

PMID- 28516450
TI  - Synthesis and multi-spectroscopic study on DNA-binding, cleavage and biological
      properties of M(II) complexes based on N2 O2 donor Schiff base ligand.
AB  - A novel Schiff base, (S,Z)-4-(methylthio)-2-((3-oxo-2,3-dihydro-1H-inden-1
      ylidene)amino)butanoic acid (L) and four M(II) complexes (where M = Co, Cu, Ni
      and Zn) were synthesized and characterized. The DNA-binding characteristics of
      the complexes were investigated using various spectroscopic methods and viscosity
      measurements. Analysis of the results suggests that all the complexes bind to
      calf thymus DNA via intercalation. Among the four, Cu(II) complex was found to
      promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm.
      These complexes also exhibit good antioxidant activities against 2,2-diphenyl-1
      picrylhydrazyl radical. In vitro antibacterial and antifungal assay indicates
      that these complexes are good antimicrobial agents.

PMID- 28516451
TI  - Evidence that eating baked egg or milk influences egg or milk allergy resolution:
      a systematic review.
AB  - BACKGROUND: It has been proposed that the frequent ingestion of baked hen's egg
      or cow's milk accelerates the resolution of hen's egg or cow's milk allergy. This
      practice is being introduced into clinical practice. OBJECTIVE: To systematically
      review the evidence to determine whether the introduction of baked hen's egg or
      cow's milk into the diet of children with hen's egg or cow's milk allergies
      respectively leads to a larger proportion of children outgrowing these allergies
      than expected. METHODS: A systematic review of the literature was conducted in
      Medline, Embase and CINAHL. The inclusion criteria were as follows: randomized
      control trials, case-control or cohort studies; children aged 0-18 years with
      hen's egg or cow's milk allergy; baked hen's egg or cow's milk intervention with
      or without a comparator; and resolution of the hen's egg or cow's milk allergy as
      determined by food challenge as the outcome. Studies were critically appraised
      using the quality assessment tool for quantitative studies. PROSPERO reference
      CRD42015026029. RESULTS: We identified 851 and 2816 hen's egg and cow's milk
      articles respectively. Only three hen's egg and three cow's milk studies
      fulfilled our pre-specified inclusion criteria. The studies concluded that baked
      products either increased the likelihood of the resolution of allergy or
      accelerated resolution. However, when critiqued, all studies were classified as
      weak because they were observational, lacking an appropriate control group; this
      brings into doubt the study's conclusions. There were a number of examples of
      severe reactions to baked products. CONCLUSION: There is little evidence to
      address the hypothesis that the ingestion of baked hen's egg or cow's milk
      results in more patients outgrowing their hen's egg or cow's milk allergy
      respectively. Data are required from a trial comparing the resolution rates of
      baked-tolerant participants who are randomized to ingest or avoid baked products
      to assess the accuracy of this hypothesis.

PMID- 28516453
TI  - DBA/2J mouse model for experimental glaucoma: pitfalls and problems.
AB  - BACKGROUND: The DBA/2J mouse has been described as a model for congenital
      experimental glaucoma. It develops anterior segment anomalies with synechiae and
      pigment dispersion leading to raised intraocular pressure and glaucomatous
      damage. However, there are serious practical considerations when using this model
      in longitudinal studies. METHODS: We followed 118 mice from 12-48 weeks of age in
      a pharmaceutical trial. Here we report on the findings in control animals (n =
      37). Intraocular pressure was measured weekly, electrophysiology and optical
      coherence tomography every 6 weeks. A subset also had invasive intraocular
      pressure measurements performed prior to euthanasia. RESULTS: Although
      intraocular pressure eventually rose by 9 months in most animals, tonometry was
      complicated by corneal calcification in the majority of animals rendering
      intraocular pressure measurement unreliable. Invasive intraocular pressure did
      not correlate with non-invasive measures. Loss of scotopic threshold response and
      thinning of inner retinal layers on optical coherence tomography was observed
      over time, suggesting glaucomatous damage, but this occurred in some animals
      without raised intraocular pressure. Poor pupil dilation significantly affected
      electrophysiology, optical coherence tomography and fundus imaging; 22% of
      animals developed major systemic complications leading to high dropout rate.
      CONCLUSIONS: The DBA/2J experimental glaucoma model shows variability in
      expression, and its pathological changes cause major difficulties in assessing
      disease progression. From our experience, the model presents significant
      challenges for drug studies in glaucoma, as there are many confounding factors:
      difficulty with accurate intraocular pressure measurement, in vivo imaging, and
      electrophysiology recording and a high dropout rate. In addition, there may be an
      underlying neurodegenerative process independent of intraocular pressure.

PMID- 28516452
TI  - Correlation between socio-economic status and atopic dermatitis in Korean adults:
      the Korea national health and nutrition examination survey (2007-2014).
AB  - INTRODUCTION: Atopic dermatitis (AD) is one of the most common allergic diseases.
      Its prevalence has been increasing in recent decades. Socio-economic status is
      well-known risk factor of allergic diseases. OBJECTIVE: This study was performed
      to investigate the relationship between socio-economic status and AD in Korean
      adults. METHODS: Data were acquired from 47 351 men and women, >=19 years of age
      who participated in the Korea National Health and Nutrition Examination Surveys
      (KNHANES) conducted from 2007 to 2014. The presence of AD was based on self
      reported physician diagnosis of AD in the Health Interview Surveys. RESULTS: The
      prevalence of AD was 3.1%, which decreased with increasing age. In univariate
      analysis, adults with AD were prone to be female, younger, never-married, well
      educated, lower household members, and urban dwelling (all P < 0.01). Monthly
      family income and smoking status were not associated with the presence of AD. The
      prevalence of hypertension, diabetes mellitus and asthma was higher in AD
      subjects (all P < 0.01), while obesity was not associated with adult AD. After
      adjusting for confounders, logistic regression analysis showed female sex
      (adjusted odds ratio [aOR]: 1.483, 95% CI: 1.268-1.734), age (P < 0.01), marital
      status (Single: aOR: 1.307, 95% CI: 1.012-1.690; Never-married: aOR: 1.938, 95%
      CI: 1.513-2.482), urban residence (aOR: 1.281, 95% CI: 1.045-1.569) and asthma
      (aOR: 1.788, 95% CI: 1.416-2.258) were associated with higher prevalence of AD
      (all P < 0.01). CONCLUSION: Female sex, age, marital status, urban residence, and
      the presence of asthma are important risk factors of the prevalence of AD in
      Korean adults.

PMID- 28516456
TI  - Description of embryonic development and ultrastructure in miracidia of
      Cardiocephaloides longicollis (Digenea, Strigeidae) in relation to active host
      finding strategy in a marine environment.
AB  - The functional ultrastructure and embryonic development of miracidia in naturally
      released eggs of the trematode Cardiocephaloides longicollis were studied using
      light and transmission electron microscopy. This species has operculated eggs and
      embryogenesis occurs in the marine environment before an actively infecting
      ciliated miracidium hatches. Six different developmental stages were identified.
      The lack of pores in the eggshell indicates its impermeability and the
      miracidium's dependency on glycogen nutritive reserves, contained in numerous
      vitellocytes in early embryos. As the development advances, these merge into
      larger vitelline vacuoles that encircle the miracidium and may aid its hatching.
      Tissue and primary organ differentiation were observed in advanced stages, i.e.,
      terebratorium, glands, cerebral ganglion, peripheral sensory endings, and
      eyespots. The anterior part of the body contains a single apical and paired
      lateral glands, as well as two types of sensory endings, which permit location,
      adhesion, and penetration of the host. No previous studies describe the embryonic
      development and ultrastructure of miracidia in strigeids, however, some of the
      structural features shared with other, well described species with unknown life
      cycles are emphasised. This study highlights that ultrastructural data have to be
      interpreted in relation to parasite biology to understand the structural
      requirements of specific parasite strategies.

PMID- 28516455
TI  - Heterogeneity of Purkinje cell simple spike-complex spike interactions: zebrin-
      and non-zebrin-related variations.
AB  - KEY POINTS: Cerebellar Purkinje cells (PCs) generate two types of action
      potentials, simple and complex spikes. Although they are generated by distinct
      mechanisms, interactions between the two spike types exist. Zebrin staining
      produces alternating positive and negative stripes of PCs across most of the
      cerebellar cortex. Thus, here we compared simple spike-complex spike interactions
      both within and across zebrin populations. Simple spike activity undergoes a
      complex modulation preceding and following a complex spike. The amplitudes of the
      pre- and post-complex spike modulation phases were correlated across PCs. On
      average, the modulation was larger for PCs in zebrin positive regions.
      Correlations between aspects of the complex spike waveform and simple spike
      activity were found, some of which varied between zebrin positive and negative
      PCs. The implications of the results are discussed with regard to hypotheses that
      complex spikes are triggered by rises in simple spike activity for either motor
      learning or homeostatic functions. ABSTRACT: Purkinje cells (PCs) generate two
      types of action potentials, called simple and complex spikes (SSs and CSs). We
      first investigated the CS-associated modulation of SS activity and its
      relationship to the zebrin status of the PC. The modulation pattern consisted of
      a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and
      finally a late inhibition of SS activity for both zebrin positive (Z+) and
      negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells.
      Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the
      modulation were correlated across PCs. In contrast, correlations between
      modulation phases across CSs of individual PCs were generally weak. Next, the
      relationship between CS spikelets and SS activity was investigated. The number of
      spikelets/CS correlated with the average SS firing rate only for Z+ cells. In
      contrast, correlations across CSs between spikelet numbers and the amplitudes of
      the SS modulation phases were generally weak. Division of spikelets into likely
      axonally propagated and non-propagated groups (based on their interspikelet
      interval) showed that the correlation of spikelet number with SS firing rate
      primarily reflected a relationship with non-propagated spikelets. In sum, the
      results show both zebrin-related and non-zebrin-related physiological
      heterogeneity in SS-CS interactions among PCs, which suggests that the cerebellar
      cortex is more functionally diverse than is assumed by standard theories of
      cerebellar function.

PMID- 28516454
TI  - A multiscale computational modelling approach predicts mechanisms of female sex
      risk in the setting of arousal-induced arrhythmias.
AB  - KEY POINTS: This study represents a first step toward predicting mechanisms of
      sex-based arrhythmias that may lead to important developments in risk
      stratification and may inform future drug design and screening. We undertook
      simulations to reveal the conditions (i.e. pacing, drugs, sympathetic
      stimulation) required for triggering and sustaining reentrant arrhythmias. Using
      the recently solved cryo-EM structure for the Eag-family channel as a template,
      we revealed potential interactions of oestrogen with the pore loop hERG mutation
      (G604S). Molecular models suggest that oestrogen and dofetilide blockade can
      concur simultaneously in the hERG channel pore. ABSTRACT: Female sex is a risk
      factor for inherited and acquired long-QT associated torsade de pointes (TdP)
      arrhythmias, and sympathetic discharge is a major factor in triggering TdP in
      female long-QT syndrome patients. We used a combined experimental and
      computational approach to predict 'the perfect storm' of hormone concentration,
      IKr block and sympathetic stimulation that induces arrhythmia in females with
      inherited and acquired long-QT. More specifically, we developed mathematical
      models of acquired and inherited long-QT syndrome in male and female ventricular
      human myocytes by combining effects of a hormone and a hERG blocker, dofetilide,
      or hERG mutations. These 'male' and 'female' model myocytes and tissues then were
      used to predict how various sex-based differences underlie arrhythmia risk in the
      setting of acute sympathetic nervous system discharge. The model predicted
      increased risk for arrhythmia in females when acute sympathetic nervous system
      discharge was applied in the settings of both inherited and acquired long-QT
      syndrome. Females were predicted to have protection from arrhythmia induction
      when progesterone is high. Males were protected by the presence of testosterone.
      Structural modelling points towards two plausible and distinct mechanisms of
      oestrogen action enhancing torsadogenic effects: oestradiol interaction with hERG
      mutations in the pore loop containing G604 or with common TdP-related blockers in
      the intra-cavity binding site. Our study presents findings that constitute the
      first evidence linking structure to function mechanisms underlying female
      dominance of arousal-induced arrhythmias.

PMID- 28516457
TI  - Computed tomography or necropsy diagnosis of multiple bullae and the treatment of
      pneumothorax in rhesus macaques (Macaca mulatta).
AB  - Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine.
      We diagnosed multiple pulmonary bullae combined with or without pneumothorax by
      computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta)
      imported from China. Two of seven rhesus macaques accompanied by pneumothorax
      were cured by fixation of ruptured lung through left or right 3rd intercostal
      thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae,
      was not detected from tracheobronchiolar lavage. To the best of our knowledge,
      this is the first case report on the CT-aided diagnosis of pulmonary bullae and
      the successful treatment of combined pneumothorax by thoracotomy in non-human
      primates (NHPs).

PMID- 28516458
TI  - YH12852, a potent and highly selective 5-HT4 receptor agonist, significantly
      improves both upper and lower gastrointestinal motility in a guinea pig model of
      postoperative ileus.
AB  - BACKGROUND: Postoperative ileus (POI) is a transient gastrointestinal (GI)
      dysmotility that commonly develops after abdominal surgery. YH12852, a novel,
      potent and highly selective 5-hydroxytryptamine 4 (5-HT4 ) receptor agonist, has
      been shown to improve both upper and lower GI motility in various animal studies
      and may have applications for the treatment of POI. Here, we investigated the
      effects and mechanism of action of YH12852 in a guinea pig model of POI to
      explore its therapeutic potential. METHODS: The guinea pig model of POI was
      created by laparotomy, evisceration, and gentle manipulation of the cecum for 60
      seconds, followed by closure with sutures under anesthesia. Group 1 received an
      oral administration of vehicle or YH12852 (1, 3, 10 or 30 mg/kg) only, while POI
      Group 2 was intraperitoneally pretreated with vehicle or 5-HT4 receptor
      antagonist GR113808 (10 mg/kg) prior to oral dosing of vehicle or YH12852 (3 or
      10 mg/kg). Upper GI transit was evaluated by assessing the migration of a
      charcoal mixture in the small intestine, while lower GI transit was assessed via
      measurement of fecal pellet output (FPO). KEY RESULTS: YH12852 significantly
      accelerated upper and lower GI transit at the doses of 3, 10, and 30 mg/kg and
      reached its maximal effect at 10 mg/kg. These effects were significantly blocked
      by pretreatment of GR113808 10 mg/kg. CONCLUSION AND INFERENCES: Oral
      administration of YH12852 significantly accelerates and restores delayed upper
      and lower GI transit in a guinea pig model of POI. This drug may serve as a
      useful candidate for the treatment of postoperative ileus.

PMID- 28516460
TI  - Taxane-Grafted Metal-Oxide Nanoparticles as a New Theranostic Tool against
      Cancer: The Promising Example of Docetaxel-Functionalized Titanate Nanotubes on
      Prostate Tumors.
AB  - The combination of anticancer drugs and metal oxide nanoparticles is of great
      interest in cancer nanomedicine. Here, the development of a new nanohybrid,
      titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are
      conjugated by covalent linkages. Unlike most nanoparticles currently being
      developed for biomedical purposes, TiONts present a needle-shaped morphology. The
      surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero
      bifunctional polymer (polyethylene glycol) to create well-dispersed and
      biocompatible nanovectors. The prefunctionalized surface of this scaffold has
      valuable attachments to graft therapeutic agents (DTX in our case) as well as
      chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to
      monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have
      demonstrated that the association between TiONts and DTX shows cytotoxic activity
      against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts
      without DTX do not. Finally, the first in vivo tests with intratumoral injections
      show that more than 70% of TiONts nanovectors are retained within the tumor for
      at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is
      significantly slower than that in mice receiving free DTX. This nanohybrid can
      thus become a promising new tool in biomedicine to fight against prostate cancer.

PMID- 28516461
TI  - Effects of High-g Impact on Physical, Electrical, and Optical Characteristics of
      Light-Emitting Diodes.
AB  - Previously, one of the tools available in automotive or aircraft accident
      analysis was the examination of the indicator bulbs. Currently, indicator bulbs
      have been largely replaced by light-emitting diodes (LEDs). Here a series of
      studies was carried out on impact effects on LEDs to determine whether their
      properties change after impact, and whether it is related to its working status
      (lit or unlit). The LEDs were measured before mechanical shock with a series of
      tests, including current-voltage, current-light, bandwidth, subject to impact
      ranging from 450 g to 2000 g, and then retested. The tests showed consistent
      slight but statistically significant increases in forward voltages at a given
      current after impact, which could be used to estimate the impact. Some LEDS were
      imaged before and after impact with thermal and X-ray imaging, but no mechanical
      changes were seen. It was not possible to determine the LED's working status from
      these test results.

PMID- 28516459
TI  - PP2A deactivation is a common event in oral cancer and reactivation by FTY720
      shows promising therapeutic potential.
AB  - Protein phosphatase 2A (PP2A) is a tumor suppressor gene, that has been
      frequently deactivated in many types of cancer. However, its molecular and
      clinical relevance in oral squamous cell carcinoma (OSCC) remain unclear. Here we
      show that, PP2A deactivation is a common event in oral cancer cells and
      hyperphosphorylation in its tyrosine-307 (Y307) residue contributes to PP2A
      deactivation. PP2A restoration by FTY720 treatment reduced cell growth and
      decreased GSK-3beta phosphorylation without significantly altering other PP2A
      targets. We further detected PP2A phosphorylation in 262 OSCC tissues. Increased
      expression of p-PP2A in the tumor tissues was significantly correlated with
      higher N2/N3-stage (aOR = 2.1, 95%CI: 1.2-3.8). Patients with high p-PP2A
      expression had lower overall survival rates than those with low expression.
      Hazard ratio analysis showed that, high p-PP2A expression was significantly
      associated with mortality density (aOR = 2.2, 95%CI: 1.2-4.0) and lower 10-year
      overall survival (p = 0.027) in lymph node metastasis. However, no interaction
      was observed between p-PP2A expression and lymph node metastasis. All our results
      suggest that PP2A is frequently deactivated in oral cancer and determines poor
      outcome, restoring its expression by FTY720 can be an alternative therapeutic
      approach in OSCC.

PMID- 28516463
TI  - Novel mutation of OCRL1 in Lowe syndrome with multiple epidermal cysts.

PMID- 28516462
TI  - Metastatic right atrial hepatoma.

PMID- 28516464
TI  - The Blood Donation Ambivalence Survey: measuring conflicting attitudes about
      giving blood.
AB  - OBJECTIVES: This study was designed to develop and conduct initial validation
      testing for a novel measure of ambivalence about donating blood. BACKGROUND:
      Previous studies of living organ, bone marrow and stem cell donors have
      identified donation-related ambivalence as a predictor of decisions about
      donation and post-donation outcomes. Ambivalence about blood donation has not
      received the same attention. METHODS: In Study 1, a sample of young adults (N =
      396) were administered test items of ambivalence, and exploratory (EFA) and
      confirmatory factor analyses (CFA) were performed to identify the Blood Donation
      Ambivalence Survey. In Study 2, a separate sample of young adults (N = 241)
      completed the Blood Donation Ambivalence Survey in addition to questionnaires
      assessing known predictors of blood donation. RESULTS: Exploratory and
      confirmatory factor analyses indicated a two-factor structure reflecting
      commitment to donating blood and indecision about giving blood. The commitment
      subscale was positively related to known predictors of increased donation
      behaviour (e.g. donation intention, self-efficacy), whereas the indecision
      subscale was positively related to known predictors of decreased donation
      behaviour (e.g. donation anxiety, negative affect). Furthermore, a history of
      blood donation was associated with greater commitment and less indecision.
      CONCLUSIONS: The present findings provide strong initial support for the
      reliability and validity of a novel measure of blood donor ambivalence.

PMID- 28516465
TI  - MAKINGtheLINK: A school-based intervention to improve help-seeking for substance
      use problems.
AB  - BACKGROUND: Many young people are reluctant to seek professional help for alcohol
      and other substance use problems, preferring to rely on family and friends.
      MAKINGtheLINK is a school-based intervention that teaches adolescents how to help
      their peers overcome barriers to engaging with professional help. The current
      study examined the effect of the MAKINGtheLINK programme in a sample of 12- to 15
      year-old students. METHODS: Participants included 247 Grade 8 students (49% male,
      51% female) recruited from 3 schools in Victoria, Australia. Participants
      completed questionnaires measuring barriers to professional help-seeking, help
      seeking intentions and confidence to seek help at 3 time points (pre
      intervention, post-intervention and 6-week follow-up). A non-controlled repeated
      measures design was used to assess the effect of the programme on help-seeking
      across time points. RESULTS: The programme decreased barriers, increased
      intentions to seek help from formal sources, decreased intentions to seek help
      from family and increased confidence to seek help for a peer. The decrease in
      barriers was maintained at the 6-week follow-up, as were decreased intentions to
      seek help from family members, and increased intentions to seek help from school
      counsellors and alcohol and drug workers. The effects of the intervention did not
      differ substantially between males and females. CONCLUSIONS: The MAKINGtheLINK is
      the first intervention to focus on overcoming barriers to help-seeking for
      substance use problems by helping adolescents develop skills to support their
      peers. The intervention has promise as a means of facilitating help-seeking
      during adolescence, although further research is needed to test its effectiveness
      in a more rigorous design.

PMID- 28516466
TI  - Bioinspired Synthesis of Cu2+ -Modified Covalent Triazine Framework: A New Highly
      Efficient and Promising Peroxidase Mimic.
AB  - Artificial enzymes is an emerging field of research owing to the remarkable
      advantages of enzyme mimics over their natural counterpart, including tunable
      catalytic efficiencies, lower cost, ease of preparation, and excellent tolerance
      to variations of the reaction system. Herein, we report an efficient peroxidase
      mimic based on a copper-modified covalent triazine framework (CCTF). Owing to its
      unique specific surface area, atomically dispersed active Cu sites, efficient
      electron transfer, and enhanced photo-assisted enzyme-like activity, the CCTF
      showed enhanced peroxidase-like enzyme activity. Therefore, copper modification
      represents an effective route to tailor the peroxidase-like activity of the
      covalent triazine frameworks. Furthermore, the mechanism of the enhanced
      peroxidase-like activity and stability of the CCTF were investigated. As a proof
      of concept, the CCTF was used for the colorimetric detection of H2 O2 and
      decomposition of organic pollutants. This work provides a new strategy for the
      design of enzyme mimics with a broad range of potential applications.

PMID- 28516467
TI  - Lymph Vessel Thrombus Detection in Cervical Lymphedema: A Case Series.
AB  - Although thrombosis in the terminal part of thoracic duct has been described in
      patients with head and neck cancer and upper vein thrombosis, normally medical
      imaging is not successful in depicting such lymphatic thrombosis. This case
      series is about three patients with acute onset of cervical lymphedema following
      minor trauma or exceptional physical strain. Using high-resolution ultrasound, it
      was possible to detect a thrombus formation in the terminal parts of the thoracic
      duct or the lymph duct. Within a few weeks all patients recovered without relapse
      for several years.

PMID- 28516468
TI  - Association between the frequency and autonomy of social participation and self
      rated health.
AB  - AIM: Although numerous studies have reported that social participation (SP) has
      favorable effects on older people's health, no studies have focused on the
      autonomy of SP. We investigated the cross-sectional relationship between the
      type, frequency, and autonomy of SP and self-rated health (SRH). METHODS: A
      postal survey was mailed to 19 354 citizens born between 1945 and 1949 in a city
      in Nara prefecture (response rate: 65.9%). A total of 12 157 respondents (5114
      men and 7043 women) with independent basic activities of daily living made up the
      analytical participants. Six types of SP were measured: volunteer groups, sports
      groups, hobby groups, senior citizens' clubs, neighborhood community associations
      and cultural groups. Using multiple logistic regressions, we calculated the odds
      ratio for poor SRH, with non-participation as the reference. Covariates included
      age, family size, body mass index, comorbidities, smoking, drinking, walking,
      depression and cognitive function. RESULTS: Adjusted odds ratios for poor SRH
      decreased with more frequent SP or with more voluntary SP among both sexes, but
      this dose-response relationship was stronger in women than in men. After mutual
      adjustment for the frequency and autonomy of SP, voluntary SP had stronger
      effects on SRH than frequent SP, especially in sports and hobby groups among men,
      and in volunteer and hobby groups among women. For cultural groups, women with
      frequent and voluntary SP had positive effects on SRH, but frequent and
      obligatory SP had negative effects on men. CONCLUSIONS: The present results imply
      that encouraging voluntarily chosen SP rather than frequent SP might be a key
      point for successful aging. Geriatr Gerontol Int 2017; 17: 2537-2544.

PMID- 28516469
TI  - Doxycycline as an anti-inflammatory agent: updates in dermatology.
AB  - Doxycycline, a tetracycline antibiotic, is widely used in the field of
      dermatology for its antibiotic properties, anti-inflammatory properties and good
      safety profile. Over the past decades, numerous studies have clarified some of
      the anti-inflammatory mechanisms of doxycycline. In this review article, we aimed
      to provide an update on recent data on the anti-inflammatory properties of
      doxycycline and its potential role in cutaneous inflammatory diseases. Better
      understanding of these mechanisms might offer the practicing clinicians a better
      use of this therapeutic tool. In addition, research in this field could help
      clarify pathogenic aspects of inflammatory dermatologic diseases responsive to
      this medication. Further research is needed to fully elucidate the potential of
      doxycycline as an anti-inflammatory agent, and the development of new topical
      vehicles could open ways to new therapeutic possibilities for dermatologists.

PMID- 28516470
TI  - Survived so what? Identifying priorities for research with children and families
      post-paediatric intensive care unit.
AB  - The involvement of patients and the public in the development, implementation and
      evaluation of health care services and research is recognized to have tangible
      benefits in relation to effectiveness and credibility. However, despite >96% of
      children and young people surviving critical illness or injury, there is a
      paucity of published reports demonstrating their contribution to informing the
      priorities for aftercare services and outcomes research. We aimed to identify the
      service and research priorities for Paediatric Intensive Care Unit survivors with
      children and young people, their families and other stakeholders. We conducted a
      face-to-face, multiple-stakeholder consultation event, held in the Midlands (UK),
      to provide opportunities for experiences, views and priorities to be elicited.
      Data were gathered using write/draw and tell and focus group approaches. An
      inductive content analytical approach was used to categorize and conceptualize
      feedback. A total of 26 individuals attended the consultation exercise, including
      children and young people who were critical care survivors; their siblings;
      parents and carers; health professionals; academics; commissioners; and service
      managers. Consultation findings indicated that future services, interventions and
      research must be holistic and family-centred. Children and young people advisors
      reported priorities that focused on longer-term outcomes, whereas adult advisors
      identified priorities that mapped against the pathways of care. Specific
      priorities included developing and testing interventions that address unmet
      communication and information needs. Furthermore, initiatives to optimize the
      lives and longer-term functional and psycho-social outcomes of Paediatric
      Intensive Care Unit survivors were identified. This consultation exercise
      provides further evidence of the value of meaningful patient and public
      involvement in identifying the priorities for research and services for
      Paediatric Intensive Care Unit survivors and illuminates differences in proposed
      priorities between children, young people and adult advisors.

PMID- 28516471
TI  - Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal
      abrasions.
AB  - BACKGROUND: Traumatic corneal abrasions are relatively common and there is a lack
      of consensus about analgesia in their management. It is therefore important to
      document the clinical efficacy and safety profile of topical ophthalmic non
      steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal
      abrasions. OBJECTIVES: To identify and evaluate all randomised controlled trials
      (RCTs) comparing the use of topical NSAIDs with placebo or any alternative
      analgesic interventions in adults with traumatic corneal abrasions (including
      corneal abrasions arising from foreign body removal), to reduce pain, and its
      effects on healing time. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and
      Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017),
      Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health
      Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for
      Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March
      2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry
      (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov
      (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International
      Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched
      30 March 2017. We did not use any date or language restrictions in the electronic
      searches for trials.We checked the reference lists of identified trials to search
      for further potentially relevant studies. SELECTION CRITERIA: RCTs comparing
      topical NSAIDs to placebo or any alternative analgesic interventions in adults
      with traumatic corneal abrasions. DATA COLLECTION AND ANALYSIS: Two review
      authors independently performed data extraction and assessed risks of bias in the
      included studies. We rated the certainty of the evidence using GRADE. MAIN
      RESULTS: We included nine studies that met the inclusion criteria, reporting data
      on 637 participants.The studies took place in the UK, USA, Israel, Italy, France
      and Portugal. These studies compared five types of topical NSAIDs (0.1%
      indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1%
      diclofenac) to control (consisting of standard care and in four studies used
      placebo eye drops). Overall, the studies were at an unclear or high risk of bias
      (particularly selection and reporting bias). None of the included studies
      reported the primary outcome measures of this review, namely participant-reported
      pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials,
      that included data on 481 participants receiving NSAIDs or control
      (placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as
      a proxy measure of pain control. Topical NSAIDs were associated with a reduction
      in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95%
      confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4
      out of 10 people in the control group used rescue analgesia at 24 hours. No data
      were available on the use of analgesia at 48 or 72 hours.One trial (28
      participants) reported on the proportion of abrasions healed after 24 and 48
      hours. These outcomes were similar in both arms of the trial. (at 24 hours RR
      1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence).
      In the control group nine out of 10 abrasions were healed within 24 hours and all
      were healed by 48 hours. Complications of corneal abrasions were reported in 6
      studies (609 participants) and were infrequently reported (4 complications, 1 in
      NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent
      corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible
      drug-related adverse events (AEs) were reported in two trials (163 participants),
      with the number of adverse events low (4 AEs, 3 in NSAID group, including
      discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria,
      and 1 in the control group, corneal abscess) very low-certainty evidence.
      AUTHORS' CONCLUSIONS: The findings of the included studies do not provide strong
      evidence to support the use of topical NSAIDs in traumatic corneal abrasions.
      This is important, since NSAIDs are associated with a higher cost compared to
      oral analgesics. None of the trials addressed our primary outcome measure of
      participant-reported pain intensity reduction of 30% or more or 50% or more at 24
      hours.

PMID- 28516472
TI  - Nasal decontamination for the prevention of surgical site infection in
      Staphylococcus aureus carriers.
AB  - BACKGROUND: Surgical site infection rates in the month following surgery vary
      from 1% to 5%. Due to the large number of surgical procedures conducted annually,
      the costs of these surgical site infections (SSIs) can be considerable in
      financial and social terms. Nasal decontamination using antibiotics or
      antiseptics is performed to reduce the risk of SSIs by preventing organisms from
      the nasal cavity being transferred to the skin where a surgical incision will be
      made. Staphylococcus aureus (S aureus) colonises the nasal cavity and skin of
      carriers and can cause infection in open or unhealed surgical wounds. S aureus is
      the leading nosocomial (hospital-acquired) pathogen in hospitals worldwide. The
      potential effectiveness of nasal decontamination of S aureus is thought to be
      dependent on both the antibiotic/antiseptic used and the dose of application;
      however, it is unclear whether nasal decontamination actually reduces
      postoperative wound infection in S aureus carriers. OBJECTIVES: To assess the
      effects of nasal decontamination on preventing surgical site infections (SSIs) in
      people who are S aureus carriers undergoing surgery. SEARCH METHODS: In September
      2016 we searched the Cochrane Wounds Specialised Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL) (the Cochrane Library), Ovid MEDLINE,
      Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO
      CINAHL Plus. We also searched three clinical trial registries and the references
      of included studies and relevant systematic reviews. There were no restrictions
      based on language, date of publication or study setting. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) which enrolled S aureus carriers with any
      type of surgery and assessed the use of nasal decontamination with
      antiseptic/antibiotic properties were included in the review. DATA COLLECTION AND
      ANALYSIS: Two review authors independently performed study selection, data
      extraction, risk of bias assessment and GRADE assessment. MAIN RESULTS: We
      located two studies (291 participants) for inclusion in this review. The trials
      were clinically heterogeneous with differences in duration of follow-up, and
      nasal decontamination regimens. One study compared mupirocin (2% contained in a
      base of polyethylene glycol 400 and polyethylene glycol 3350) with a placebo in
      elective cardiac surgery patients; and one study compared Anerdian (iodine 0.45%
      to 0.57% (W/V), chlorhexidine acetate 0.09% to 0.11% (W/V)) with no treatment
      also in cardiac surgery patients. The trials reported limited outcome data on
      SSI, adverse events and secondary outcomes (e.g. S aureus SSI, mortality).
      Mupirocin compared with placeboThis study found no clear difference in SSI risk
      following use of mupirocin compared with placebo (1 trial, 257 participants);
      risk ratio (RR) 1.60, 95% confidence interval (CI) 0.79 to 3.25 based on 18/130
      events in the mupirocin group and 11/127 in the control group; low-certainty
      evidence (downgraded twice due to imprecision). Anerdian compared with no
      treatmentIt is uncertain whether there is a difference in SSI risk following
      treatment with Anerdian compared with no treatment (1 trial, 34 participants); RR
      0.89, 95% CI 0.06 to 13.08 based on 1/18 events in the Anerdian group and 1/16 in
      the control group; very low certainty evidence (downgraded twice due to
      imprecision and once due to risk of bias). AUTHORS' CONCLUSIONS: There is
      currently limited rigorous RCT evidence available regarding the clinical
      effectiveness of nasal decontamination in the prevention of SSI. This limitation
      is specific to the focused question our review addresses, looking at nasal
      decontamination as a single intervention in participants undergoing surgery who
      are known S aureus carriers. We were only able to identify two studies that met
      the inclusion criteria for this review and one of these was very small and poorly
      reported. The potential benefits and harms of using decontamination for the
      prevention of SSI in this group of people remain uncertain.

PMID- 28516473
TI  - A ratiometric fluorescent chemosensor for the detection of cysteine in aqueous
      solution at neutral pH.
AB  - A ratiometric fluorescent chemosensor 2-(2'-hydroxy-3'-formyl-5'
      methoxyphenyl)benzothiazole (1) was developed for the detection of cysteine
      (Cys). In aqueous solution at neutral pH, 1 exhibited a ratiometric fluorescent
      response to Cys with a remarkable red-to-green shift in the emission wavelength.
      This fluorescence change was attributed to the cyclization reaction between the
      formyl group in 1 and the amino and sulfhydryl group in Cys in a stoichiometry of
      1: 1 according to the proposed mechanism. At neutral pH, 1 displayed a
      significant fluorescence ratio signal enhancement with the addition of Cys.
      Furthermore, 1 showed good selectivity toward Cys. The detection limit and linear
      range were 5.6 and 0-100 MUmol/L, respectively, which demonstrated that 1 could
      recognize relatively low concentrations of Cys and is a good candidate for
      applications in detecting Cys.

PMID- 28516475
TI  - Evaluation of detection distance-dependent reflectance spectroscopy for the
      determination of the sun protection factor using pig ear skin.
AB  - Determination of sun protection factors (SPFs) is currently an invasive method,
      which is based on erythema formation (phototest). Here we describe an optical
      setup and measurement methodology for the determination of SPFs based on diffuse
      reflectance spectroscopy, which measures UV-reflectance spectra at 4 distances
      from the point of illumination. Due to a high spatial variation of the
      reflectance data, most likely due to inhomogeneities of the sunscreen
      distribution, data of 50 measurement positions are averaged. A dependence of the
      measured SPF on detection distance is significant for 3 sunscreens, while being
      inconclusive for 2 sunscreens due to high inter-sample variations. Using pig ear
      skin samples (n=6), the obtained SPF of 5 different commercial sunscreens
      corresponds to the SPF values of certified test institutes in 3 cases and is
      lower for 2 sunscreens of the same manufacturer, suggesting a formulation
      specific reason for the discrepancy. The results demonstrate that the measurement
      can be performed with a UV dose below the minimal erythema dose. We conclude the
      method may be considered as a potential noninvasive in vivo alternative to the
      invasive in vivo phototest, but further tests on different sunscreen formulations
      are still necessary.

PMID- 28516476
TI  - Massive retinal gliosis with episcleral extension.

PMID- 28516474
TI  - Relationship between pain and motor and non-motor symptoms in Parkinson's
      disease.
AB  - BACKGROUND AND PURPOSE: Although female gender, depressive symptoms and medical
      conditions predisposing to pain are more common in patients with Parkinson's
      disease (PD) with pain, no study has yet explored the relationship between pain
      and other non-motor symptoms (NMS). METHODS: A total of 321 consecutive patients
      with PD [190 men/131 women aged 68.3 (SD 9.2) years] attending four Italian
      movement disorder clinics were studied. Demographic/clinical data were obtained
      by a standardized interview and the NMS scale. The association of pain with motor
      and NMS was assessed by multivariable logistic regression models. RESULTS: At the
      time of the study, 180 patients with PD (56%) reported chronic pain that, in most
      cases, was described as being muscular or arthralgic pain. Pain preceded the
      onset of motor signs in 36/180 patients. In the main-effect model, factors
      independently associated with pain were female sex [odds ratio (OR), 2.1; P =
      0.01], medical conditions predisposing to pain (OR, 2.9; P < 0.001), Hoehn-Yahr
      staging (OR, 1.9; P = 0.04), motor complications (OR, 4.7; P = 0.04) and NMS
      belonging to the sleep/fatigue (OR, 1.6; P = 0.04) and mood/cognition (OR, 1.6; P
      = 0.03) domains. Most explanatory variables in the multivariable analysis were
      similarly distributed in patients in whom pain may have been related to PD or to
      a cause other than PD. CONCLUSIONS: We confirm that pain in PD is more frequent
      in women and in subjects with medical conditions predisposing to painful
      symptoms. Moreover, this strengthens the association between pain and motor
      severity measures and NMS domains, particularly sleep and mood disturbances.

PMID- 28516477
TI  - A prospective observational study on effects of fever on red cell transfusion
      outcome.
AB  - The effects of fever on red cell transfusions are not well documented. In this
      pilot study, we have compared the outcome of red-blood-cell transfusions in
      haematologic patients with and without fever. The results indicate that
      haemoglobin increment per unit is significantly lower in febrile patients
      receiving red cell transfusions than in patients without fever. These findings
      are in line with earlier findings in preclinical studies. Larger studies are
      necessary to confirm our results, and laboratory studies should be conducted to
      investigate the underlying mechanisms.

PMID- 28516478
TI  - Determination of oral bioavailability of curcuminoid dispersions and
      nanoemulsions prepared from Curcuma longa Linnaeus.
AB  - BACKGROUND: Curcuminoid from Curcuma longa Linnaeus has been demonstrated to be
      effective in anti-cancer and anti-inflammation. The objectives of the present
      study were to prepare curcuminoid dispersion and nanoemulsion from C. longa and
      determine their oral bioavailabilities in rats. RESULTS: After curcuminoid
      extraction using 99.5% ethanol, bisdemethoxycurcumin (BDMC), demethoxycurcumin
      (DMC) and curcumin were separated within 10 min by high-performance liquid
      chromatography using an Eclipse XDB-C18 column (Agilent, Palo Alto, CA, USA) and
      a gradient mobile phase of 0.1% aqueous formic acid and acetonitrile, with a flow
      rate of 1 mL min-1 , column temperature of 35  degrees C and detection wavelength
      of 425 nm. Curcuminoid nanoemulsion at a particle size of 12.1 nm and
      encapsulation efficiency 98.8% was prepared using lecithin, Tween 80 and water. A
      pharmacokinetic study in rats revealed that the parameters including Tmax , Cmax
      , t1/2 and the area under the curve were higher for curcuminoid nanoemulsions
      than for curcuminoid dispersion at the same dose employed for gavage
      administration, whereas, for intravenous injection, an opposite trend was shown.
      The oral bioavailabilities of BDMC, DMC, curcumin and total curcuminoids in
      nanoemulsion and dispersion were 34.39 and 4.65%, 39.93 and 5.49%, 47.82 and
      9.38%, and 46 and 8.7%, respectively. CONCLUSION: The results of the present
      study demonstrate a higher oral bioavailability after incorporation of
      curcuminoid into nanoemulsion, facilitating its application as a botanic drug.
      (c) 2017 Society of Chemical Industry.

PMID- 28516480
TI  - Development and feasibility of smartphone application for cognitive-behavioural
      case management of individuals with early psychosis.
AB  - BACKGROUND: This article describes the development of the smartphone application
      for cognitive-behavioural case management of young individuals with early
      psychosis and examines the acceptance and potential clinical benefits of this
      application through a pilot survey. METHODS: Gwangju Bukgu-Community Mental
      Health Center developed and launched a smartphone application (Heal Your Mind
      [HYM]) for cognitive-behavioural case management and symptom monitoring. The HYM
      application for clients includes 6 main modules including thought record, symptom
      record, daily life record, official notices, communication and scales. The key
      module is the "thought record" for self-directed cognitive-behavioural treatment.
      When the client writes and sends the self-cognitive-behavioural therapy sheet to
      the case manager, the latter receives a notification and can provide feedback in
      real time. We conducted a survey to investigate the acceptance and feasibility of
      this approach among young clients with early psychosis. RESULTS: A total of 24
      clients with early psychosis participated in this survey. More than 80% of
      participants reported that it was easy to learn to use this application, and no
      one described this application as very complicated or reported that they needed a
      long time to learn how to use it. About 80% of participants were satisfied with
      this application, and 70% reported that they received help as a result of using
      this application. CONCLUSIONS: This study suggests that this smartphone
      application is useful for young individuals with early psychosis and that it may
      contribute to the development of both young customer- and case manager-friendly
      systems for this clinical population.

PMID- 28516481
TI  - Massive mediastinal enlargement due to extramedullary haematopoiesis in a patient
      with MYH9-related thrombocytopenia.

PMID- 28516482
TI  - Multiple boli arterial spin labeling for high signal-to-noise rodent brain
      perfusion imaging.
AB  - PURPOSE: A systematic method is proposed for optimizing a promising preclinical
      arterial spin labeling (ASL) sequence based on the use of a train of adiabatic
      radiofrequency pulses labeling successive boli of blood water. METHODS: The
      sequence optimization is performed and evaluated using brain imaging experiments
      in mice and in rats. It involves the investigation of several parameters, ranging
      from the number of adiabatic pulses and labeling duration to the properties of
      the adiabatic hyperbolic secant pulses (ie, amplitude and frequency modulation).
      RESULTS: Species-dependent parameters are identified, allowing for robust fast
      optimization protocols to be introduced. The resulting optimized multiple boli
      ASL (mbASL) sequence provides with significantly higher average signal-to-noise
      ratios (SNR) per voxel volume than currently encountered in ASL studies (278 mm-3
      in mice and 172 mm-3 in rats). Comparing with the commonly used flow-sensitive
      alternating inversion recovery technique (FAIR), mbASL-to-FAIR SNR ratios reach
      203% for mice and 725% for rats. CONCLUSION: When properly optimized, mbASL can
      offer a robust, high SNR ASL alternative for rodent brain perfusion studies Magn
      Reson Med 79:1020-1030, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 28516479
TI  - Galphas signalling of the CB1 receptor and the influence of receptor number.
AB  - BACKGROUND AND PURPOSE: CB1 receptor signalling is canonically mediated through
      inhibitory Galphai proteins, but occurs through other G proteins under some
      circumstances, Galphas being the most characterized secondary pathway.
      Determinants of this signalling switch identified to date include Galphai
      blockade, CB1 /D2 receptor co-stimulation, CB1 agonist class and cell background.
      Hence, we examined the effects of receptor number and different ligands on CB1
      receptor signalling. EXPERIMENTAL APPROACH: CB1 receptors were expressed in HEK
      cells at different levels, and signalling characterized for cAMP by real-time
      BRET biosensor -CAMYEL - and for phospho-ERK by AlphaScreen. Homogenate and whole
      cell radioligand binding assays were performed to characterize AM6544, a novel
      irreversible CB1 receptor antagonist. KEY RESULTS: In HEK cells expressing high
      levels of CB1 receptors, agonist treatment stimulated cAMP, a response not known
      to be mediated by receptor number. Delta9 -THC and BAY59-3074 increased cAMP only
      in high-expressing cells pretreated with pertussis toxin, and agonists
      demonstrated more diverse signalling profiles in the stimulatory pathway than the
      canonical inhibitory pathway. Pharmacological CB1 receptor knockdown and Galphai
      1 supplementation restored canonical Galphai signalling to high-expressing cells.
      Constitutive signalling in both low- and high-expressing cells was Galphai 
      mediated. CONCLUSION AND IMPLICATIONS: CB1 receptor coupling to opposing G
      proteins is determined by both receptor and G protein expression levels, which
      underpins a mechanism for non-canonical signalling in a fashion consistent with
      Galphas signalling. CB1 receptors mediate opposite consequences in endpoints such
      as tumour viability depending on expression levels; our results may help to
      explain such effects at the level of G protein coupling.

PMID- 28516484
TI  - Incidental finding of recent parvovirus infection.

PMID- 28516483
TI  - Capabilities and limitations of DGGE for the analysis of hydrocarbonoclastic
      prokaryotic communities directly in environmental samples.
AB  - Prokaryotic communities in pristine and oil-contaminated desert soil, seawater,
      and hypersaline coastal soil were analyzed using culture-dependent and culture
      independent approaches. The former technique was the dilution-plating method. For
      the latter, total genomic DNA was extracted and the 16S rRNA genes were amplified
      using a universal bacterial primer pair and primer pairs specific for
      Actinobacteria, Gammaproteobacteria, and Archaea. The amplicons were resolved
      using denaturing gradient gel electrophoresis (DGGE) and sequenced, and the
      sequences were compared to those in GenBank. The plating method offered the
      advantages of capturing the targeted hydrocarbonoclastic microorganisms, counting
      them and providing cultures for further study. However, this technique could not
      capture more than a total of 15 different prokaryotic taxa. Those taxa belonged
      predominantly to the genera Alcanivorax, Pseudoxanthomonas, Bosea, Halomonas, and
      Marinobacter. The individual isolates in culture consumed between 19 and 50% of
      the available crude oil in 10 days. Although the culture-independent approach
      revealed much more microbial diversity, it was not problem-free. The subdivision
      primers exhibited satisfactory specificity, but they failed to capture all the
      available taxa. The universal bacterial primer pair ignored Actinobacteria
      altogether, although the primer pair specific for Actinobacteria captured many of
      them, for example, the genera Geodermatophilus, Streptomyces, Mycobacterium,
      Pontimonas, Rhodococcus, Blastococcus, Kocuria, and many others. Because most
      researchers worldwide use universal primers for PCR, this finding should be
      considered critically to avoid misleading interpretations.

PMID- 28516488
TI  - Aged care nurses' job control influence satisfaction and mental health.
AB  - BACKGROUND: Relationships exist between aged care nurses' perceptions of
      psychosocial work characteristics, job satisfaction and mental health, suggesting
      these characteristics may be important for the management of aged care services.
      AIM: An expanded demand-control-support model that included justice perceptions
      was examined to determine its impact on multiple types of psychological and
      organisational well-being outcomes (i.e. job satisfaction, psychological distress
      and depression). METHOD: Data were collected from a sample of 173 aged care
      nurses using a self-report survey and analysed using hierarchical multiple
      regression. RESULTS: A significant proportion (27-28%) of the variance in aged
      care nurses' satisfaction, depression and psychological distress was explained by
      the psychosocial factors included in the model. Job control had the most
      consistent impact with direct effects on job satisfaction, psychological distress
      and depression. Informational justice was associated with both psychological
      distress and depression. CONCLUSIONS: Targeting job control may provide the
      biggest response for nurse managers in aged care, as it is likely to influence
      nurses' job satisfaction, psychological distress and depression. IMPLICATIONS FOR
      NURSING MANAGEMENT: Facility managers should implement organisational policies
      and procedures that promote higher levels of control over how nurses perform
      their work in order to improve nurse well-being in aged care settings.

PMID- 28516485
TI  - Simultaneous measurement of T2 and apparent diffusion coefficient (T2 +ADC) in
      the heart with motion-compensated spin echo diffusion-weighted imaging.
AB  - PURPOSE: To evaluate a technique for simultaneous quantitative T2 and apparent
      diffusion coefficient (ADC) mapping in the heart (T2 +ADC) using spin echo (SE)
      diffusion-weighted imaging (DWI). THEORY AND METHODS: T2 maps from T2 +ADC were
      compared with single-echo SE in phantoms and with T2 -prepared (T2 -prep)
      balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps
      from T2 +ADC were compared with conventional DWI in phantoms and in vivo. T2 +ADC
      was also demonstrated in a patient with acute myocardial infarction (MI).
      RESULTS: Phantom T2 values from T2 +ADC were closer to a single-echo SE reference
      than T2 -prep bSSFP (-2.3 +/- 6.0% vs 22.2 +/- 16.3%; P < 0.01), and ADC values
      were in excellent agreement with DWI (0.28 +/- 0.4%). In volunteers, myocardial
      T2 values from T2 +ADC were significantly shorter than T2 -prep bSSFP (35.8 +/-
      3.1 vs 46.8 +/- 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.)
      different between T2 +ADC and conventional motion-compensated DWI (1.39 +/- 0.18
      vs 1.38 +/- 0.18 mm2 /ms; P = N.S.). In the patient, T2 and ADC were both
      significantly elevated in the infarct compared with remote myocardium (T2 : 40.4
      +/- 7.6 vs 56.8 +/- 22.0; P < 0.01; ADC: 1.47 +/- 0.59 vs 1.65 +/- 0.65 mm2 /ms;
      P < 0.01). CONCLUSION: T2 +ADC generated coregistered, free-breathing T2 and ADC
      maps in healthy volunteers and a patient with acute MI with no cost in accuracy,
      precision, or scan time compared with DWI. Magn Reson Med 79:654-662, 2018. (c)
      2017 International Society for Magnetic Resonance in Medicine.

PMID- 28516487
TI  - The petrosal and bony labyrinth of Diplobune minor, an enigmatic Artiodactyla
      from the Oligocene of Western Europe.
AB  - Anoplotheriinae are Paleogene European artiodactyls that present a unique
      postcranial morphology with a tridactyl autopodium and uncommon limb orientation.
      This peculiar morphology led to various hypotheses regarding anoplotheriine
      locomotion from semiaquatic to partly arboreal or partly bipedal. The petrosal
      bone, housing the organs of balance, and hearing, offers complementary
      information to postcranial morphology on the ecology of this uncommon
      artiodactyl. Here, we investigate the middle ear and bony labyrinth of the small
      anoplotheriine Diplobune minor based on four specimens from the Early Oligocene
      locality of Itardies (Quercy, France). A macroscopic study coupled with a MUCT
      scan investigation of the petrosal anatomy provides novel information on the bony
      labyrinth, stapes, and innervation and vasculature of the inner ear of this
      enigmatic taxon. The petrosal of D. minor exhibits a mosaic of plesiomorphic
      characters and peculiar features that shed new light into the anatomy of this
      poorly studied taxon of an obscure taxonomic clade. We can confidently reject
      that D. minor was a semiaquatic species based on the petrosal morphology:
      presence of a large mastoid process and nonpachyostotic tegmen tympani do not
      support underwater hearing. On the other hand, the average semicircular canal
      radius points to a slow or medium slow agility for D. minor, and fully rejects it
      was a fast moving animal, which is congruent with its postcranial anatomy.

PMID- 28516489
TI  - Comment on "Three-dimensional ultrasonographic depiction of fetal brain blood
      vessels".

PMID- 28516490
TI  - Termination of pregnancy due to renal tract abnormalities: survey of 97 fetuses
      from a single medical center.

PMID- 28516491
TI  - Letter to the Editor: Professional nursing introductions: key to
      interprofessional collaboration.

PMID- 28516492
TI  - Telemedicine in dermatology: findings and experiences worldwide - a systematic
      literature review.
AB  - Telemedicine has become an important element of health care in many countries and
      profited from the technological progress of the last two decades. Due to the
      visual character of the dermatological specialty, teledermatology in particular
      participated in that development and is becoming a major tool in dermatological
      consultation. The objective of this article was to identify the use of
      teledermatology across the world based on published original articles. A
      systematic literature search of the MEDLINE and Embase databases for eligible
      publications (predefined inclusion and exclusion criteria) and a cross-validation
      search were conducted. Search results were reviewed systematically. The search
      resulted in 204 publications meeting the inclusion criteria for analysis. The
      highest number of published studies on teledermatology was performed in the
      United States, followed by the United Kingdom, Spain, the Netherlands, Italy and
      Austria. The majority of dermatological indications for telemedical consultations
      were not specified or included various kinds of skin diseases, followed by skin
      cancer and wounds. Research questions predominantly focused on concordance,
      effectiveness and cost-effectiveness to determine the value. Teledermatology
      proved to be a reliable consultation tool in the majority of studies. If
      specified, telemedicine was used in daily dermatological routine for patient
      management purposes, to consult patients in peripheral locations, or for medical
      support in nursing homes or home care settings. The application of
      teledermatology worldwide is highest in North American and European countries,
      while countries with poor geographical distribution of physicians seem to be
      under-represented in teledermatological use, as concluded from publication
      output. Regarding indications, comparison with classic consultation and area of
      application, most studies were of general nature. For precise determination of
      the value, systematic studies would be needed. However, teledermatology is
      already accepted as a valid tool.

PMID- 28516493
TI  - Diagnosis and treatment of dermatophytosis in dogs and cats.: Clinical Consensus
      Guidelines of the World Association for Veterinary Dermatology.
AB  - BACKGROUND: Dermatophytosis is a superficial fungal skin disease of cats and
      dogs. The most common pathogens of small animals belong to the genera Microsporum
      and Trichophyton. It is an important skin disease because it is contagious,
      infectious and can be transmitted to people. OBJECTIVES: The objective of this
      document is to review the existing literature and provide consensus
      recommendations for veterinary clinicians and lay people on the diagnosis and
      treatment of dermatophytosis in cats and dogs. METHODS: The authors served as a
      Guideline Panel (GP) and reviewed the literature available prior to September
      2016. The GP prepared a detailed literature review and made recommendations on
      selected topics. The World Association of Veterinary Dermatology (WAVD) provided
      guidance and oversight for this process. A draft of the document was presented at
      the 8th World Congress of Veterinary Dermatology (May 2016) and was then made
      available via the World Wide Web to the member organizations of the WAVD for a
      period of three months. Comments were solicited and posted to the GP
      electronically. Responses were incorporated by the GP into the final document.
      CONCLUSIONS: No one diagnostic test was identified as the gold standard.
      Successful treatment requires concurrent use of systemic oral antifungals and
      topical disinfection of the hair coat. Wood's lamp and direct examinations have
      good positive and negative predictability, systemic antifungal drugs have a wide
      margin of safety and physical cleaning is most important for decontamination of
      the exposed environments. Finally, serious complications of animal-human
      transmission are exceedingly rare.

PMID- 28516494
TI  - Recommendations for approaches to meticillin-resistant staphylococcal infections
      of small animals: diagnosis, therapeutic considerations and preventative
      measures.: Clinical Consensus Guidelines of the World Association for Veterinary
      Dermatology.
AB  - BACKGROUND: Multiple drug resistance (MDR) in staphylococci, including resistance
      to the semi-synthetic penicillinase-resistant penicillins such as meticillin, is
      a problem of global proportions that presents serious challenges to the
      successful treatment of staphylococcal infections of companion animals.
      OBJECTIVES: The objective of this document is to provide harmonized
      recommendations for the diagnosis, prevention and treatment of meticillin
      resistant staphylococcal infections in dogs and cats. METHODS: The authors served
      as a Guideline Panel (GP) and reviewed the literature available prior to
      September 2016. The GP prepared a detailed literature review and made
      recommendations on selected topics. The World Association of Veterinary
      Dermatology (WAVD) provided guidance and oversight for this process. A draft of
      the document was presented at the 8th World Congress of Veterinary Dermatology
      (May 2016) and was then made available via the World Wide Web to the member
      organizations of the WAVD for a period of three months. Comments were solicited
      and posted to the GP electronically. Responses were incorporated by the GP into
      the final document. CONCLUSIONS: Adherence to guidelines for the diagnosis,
      laboratory reporting, judicious therapy (including restriction of use policies
      for certain antimicrobial drugs), personal hygiene, and environmental cleaning
      and disinfection may help to mitigate the progressive development and
      dissemination of MDR staphylococci.

PMID- 28516495
TI  - Introduction to the World Association for Veterinary Dermatology and the Clinical
      Consensus Guidelines.

PMID- 28516496
TI  - The Impact of Childhood Obesity on Health and Health Service Use.
AB  - OBJECTIVE: To test the impact of obesity on health and health care use in
      children, by the use of various methods to account for reverse causality and
      omitted variables. DATA SOURCES/STUDY SETTING: Fifteen rounds of the Health
      Survey for England (1998-2013), which is representative of children and
      adolescents in England. STUDY DESIGN: We use three methods to account for reverse
      causality and omitted variables in the relationship between BMI and health/health
      service use: regression with individual, parent, and household control variables;
      sibling fixed effects; and instrumental variables based on genetic variation in
      weight. DATA COLLECTION/EXTRACTION METHODS: We include all children and
      adolescents aged 4-18 years old. PRINCIPAL FINDINGS: We find that obesity has a
      statistically significant and negative impact on self-rated health and a positive
      impact on health service use in girls, boys, younger children (aged 4-12), and
      adolescents (aged 13-18). The findings are comparable in each model in both boys
      and girls. CONCLUSIONS: Using econometric methods, we have mitigated several
      confounding factors affecting the impact of obesity in childhood on health and
      health service use. Our findings suggest that obesity has severe consequences for
      health and health service use even among children.

PMID- 28516497
TI  - Total Synthesis of O-GalNAcylated Antifreeze Glycoprotein using the Switchable
      Reactivity of Peptidyl-N-pivaloylguanidine.
AB  - Antifreeze glycoprotein (AFGP) is an O-glycoprotein that displays antifreeze
      activity through depression of the freezing point of water. GalNAc is a core
      sugar structure of AFGP, and contributes to induce antifreeze activity of this
      glycoprotein. However, the general functional role that this sugar plays at the
      molecular level is still unknown. To elucidate this, it is essential to determine
      the relationship between structure and activity of O-GalNAcylated AFGP using
      homogeneous glycoproteins. Thus, the total synthesis of homogeneous O
      GalNAcylated AFGP was conducted by using a unique peptide derivative: peptidyl-N
      pivaloylguanidine. It was found that peptidyl-N-pivaloylguanidine is an
      "unreactive" peptide in peptide coupling reactions but is interconvertible with a
      "reactive" peptide-alpha-thioester by means of a simple treatment under buffer
      condition at pH=7 to 8. The unique switchable reactivity of peptidyl-N
      pivaloylguanidine enabled an efficient sequential peptide coupling strategy. By
      using this strategy, various lengths of homogeneous O-GalNAcylated AFGP were
      synthesized, including one that was 120 amino acids in length, with 40 O
      GalNAcylation sites. The structural analysis by circular dichroism spectroscopy
      and evaluation of the antifreeze activity of the synthetic AFGP(GalNAc)s revealed
      that the simple O-glycosylation with GalNAc is essential for both structural and
      functional basis of AFGP to exhibit antifreeze activity.

PMID- 28516498
TI  - Non-parallel divergence across freshwater and marine three-spined stickleback
      Gasterosteus aculeatus populations.
AB  - This work investigated whether multiple freshwater populations of three-spined
      stickleback Gasterosteus aculeatus in different freshwater catchments in the
      Jutland Peninsula, Denmark, derived from the same marine populations show
      repeated adaptive responses. A total of 327 G. aculeatus collected at 13 sampling
      locations were screened for genetic variation using a combination of 70 genes
      putatively under selection and 26 neutral genes along with a marker linked to the
      ectodysplasin gene (eda), which is strongly correlated with plate armour morphs
      in the species. A highly significant genetic differentiation was found that was
      higher among different freshwater samples than between marine-freshwater samples.
      Tests for selection between marine and freshwater populations showed a very low
      degree of parallelism and no single nucleotide polymorphism was detected as
      outlier in all freshwater-marine pairwise comparisons, including the eda. This
      suggests that G. aculeatus is not necessarily the prime example of parallel local
      adaptation suggested in much of the literature and that important exceptions
      exist (i.e. the Jutland Peninsula). While marine populations in the results
      described here showed a high phenotype-genotype correlation at eda, a low
      association was found for most of the freshwater populations. The most extreme
      case was found in the freshwater Lake Hald where all low-plated phenotypes were
      either homozygotes for the allele supposed to be associated with completely
      plated morphs or heterozygotes, but none were homozygotes for the putative low
      plated allele. Re-examination of data from seven G. aculeatus studies agrees in
      showing a high but partial association between phenotype-genotype at eda in G.
      aculeatus freshwater populations and that mismatches occur everywhere in the
      European regions studied (higher in some areas, i.e. Denmark). This is
      independent of the eda marker used.

PMID- 28516499
TI  - Spectrofluorometric determination of clonazepam in dosage forms: Application to
      content uniformity testing and human plasma.
AB  - The present paper describes a developed and validated simple, highly sensitive
      and cost-effective spectrofluorometric method for determination of clonazepam
      (CNP). The proposed method depends on forming a highly fluorescent product
      through the reduction of CNP with Zn/HCl. The produced fluorophore exhibits a
      strong fluorescence at lambdaem 350 nm after excitation at lambdaex 250 nm. The
      use of carboxymethylcellulose (CMC) greatly enhanced the fluorescence intensity
      of the produced fluorophore to the extent of about 100%. Calibration curve showed
      good linear regression (r2  > 0.9998) within test ranges of 20-400 ng ml-1 with a
      lower detection limit of 0.67 ng ml-1 and lower quantification limit of 2.22 ng
      ml-1 upon using CMC. The method was successfully applied to the analysis of CNP
      in its pharmaceutical formulations and the results were in agreement with those
      obtained using a reference method. Furthermore, the content uniformity testing of
      the tablets was also performed. The application of the proposed method was
      extended to determine CNP in spiked human plasma sample as a preliminary
      investigation and the results were satisfactory.

PMID- 28516500
TI  - Healthcare utilisation, induced labour and caesarean section in the pregnancy
      after stillbirth: a prospective study.
AB  - OBJECTIVE: To investigate healthcare utilisation, induced labour and caesarean
      section (CS) in the pregnancy after stillbirth and assess anxiety and dread of
      childbirth as mediators for these outcomes. DESIGN: Population-based pregnancy
      cohort study. SETTING: The Norwegian Mother and Child Cohort Study. SAMPLE: A
      total of 901 pregnant women; 174 pregnant after stillbirth, 362 pregnant after
      live birth and 365 previously nulliparous. METHODS: Data from questionnaires
      answered in the second and third trimesters of pregnancy and information from the
      Medical Birth Registry of Norway. MAIN OUTCOME MEASURES: Self-reported assessment
      of antenatal care, register-based assessment of onset and mode of delivery.
      RESULTS: Women with a previous stillbirth had more frequent antenatal visits
      (mean 10.0; 95% CI 9.4-10.7) compared with women with a previous live birth (mean
      6.0; 95% CI 5.8-6.2) and previously nulliparous women (mean 6.3; 95% CI 6.1-6.6).
      Induced labour and CS, elective and emergency, were also more prevalent in the
      stillbirth group. The adjusted odds ratio for elective CS was 2.5 (95% CI 1.3
      5.0) compared with women with previous live birth and 3.7 (1.8-7.6) compared with
      previously nulliparous women. Anxiety was a minor mediator for the association
      between stillbirth and frequency of antenatal visits, whereas dread of childbirth
      was not a significant mediator for elective CS. CONCLUSIONS: Women pregnant after
      stillbirth were more ample users of healthcare services and more often had
      induced labour and CS. The higher frequency of antenatal visits and elective CS
      could not be accounted for by anxiety or dread of childbirth. TWEETABLE ABSTRACT:
      Women pregnant after stillbirth are ample users of healthcare services and
      interventions during childbirth.

PMID- 28516501
TI  - The histone acetyltranseferase KAT8 regulates cell differentiation by suppression
      of MN1 in AML.

PMID- 28516502
TI  - Differential effects of exposure to parasites and bacteria on stress response in
      turbot Scophthalmus maximus simultaneously stressed by low water depth.
AB  - The stress response of turbot Scophthalmus maximus was evaluated in fish
      maintained 8 days under different water depths, normal (NWD, 30 cm depth, total
      water volume 40 l) or low (LWD, 5 cm depth, total water volume 10 l), in the
      additional presence of infection-infestation of two pathogens of this species.
      This was caused by intraperitoneal injection of sublethal doses of the bacterium
      Aeromonas salmonicida subsp. salmonicida or the parasite Philasterides
      dicentrarchi (Ciliophora:Scuticociliatida). The LWD conditions were stressful for
      fish, causing increased levels of cortisol in plasma, decreased levels of
      glycogen in liver and nicotinamide adenine dinucleotide phosphate (NADP) and
      increased activities of G6Pase and GSase. The presence of bacteria or parasites
      in fish under NWD resulted in increased cortisol levels in plasma whereas in
      liver, changes were of minor importance including decreased levels of lactate and
      GSase activity. The simultaneous presence of bacteria and parasites in fish under
      NWD resulted a sharp increase in the levels of cortisol in plasma and decreased
      levels of glucose. Decreased levels of glycogen and lactate and activities of
      GSase and glutathione reductase (GR), as well as increased activities of glucose
      6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and
      levels of nicotinamide adenine dinucleotide phosphate (NADPH) occurred in the
      same fish in liver. Finally, the presence of pathogens in S. maximus under
      stressful conditions elicited by LWD resulted in synergistic actions of both type
      of stressors in cortisol levels. In liver, the presence of bacteria or parasites
      induced a synergistic action on several variables such as decreased activities of
      G6Pase and GSase as well as increased levels of NADP and NADPH and increased
      activities of GPase, G6PDH and 6PGDH.

PMID- 28516503
TI  - Sonovaginography: A Useful Technique in the Assessment of the Lower Genital
      Tract.
AB  - Conventional sonographic evaluation of the cervix and vagina is compromised by
      inattention, poor subject contrast, and obscuring artifacts. We describe a
      technique involving distention of the vaginal canal and fornices with ultrasound
      gel, providing an acoustic window for improved definition of the cervix and
      vagina. This exam is usually performed in concert with transvaginal sonography,
      but a transabdominal or transperineal approach may be more useful in selected
      scenarios. A wide variety of formerly sonographically inconspicuous conditions
      are demonstrable with this technique, many of which were undetected or
      inadequately characterized on the physical exam. Cervical polyps were the most
      commonly seen abnormality.

PMID- 28516504
TI  - Prognostic potential of midregional pro-adrenomedullin following decompensation
      for systolic heart failure: comparison with cardiac natriuretic peptides.
AB  - AIMS: Whereas guidelines recommend the routine use of natriuretic peptides (NPs)
      in heart failure (HF) care, the clinical relevance and prognostic potential of
      midregional pro-adrenomedullin (MR-proADM) is less well established. We aimed to
      compare the prognostic potential of MR-proADM after acute decompensation for
      systolic HF with that of N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      and midregional pro-atrial NP (MR-proANP), to investigate the significance of
      high/rising MR-proADM, and to evaluate the incremental prognostic yield of repeat
      measurements. METHODS AND RESULTS: The Interdisciplinary Network Heart Failure
      (INH) programme enrolled patients hospitalized for acute systolic HF and followed
      them for 18 months (100% complete). Of 1022 INH participants, 917 (68 +/- 12
      years, 28% female) who had biomaterials available were enrolled. High MR-proADM
      was associated with more impaired left ventricular function, higher comorbidity
      burden, lower doses of HF medications, and lower likelihood of left ventricular
      reverse remodelling. Compared with NPs, MR-proADM had superior prognostic
      significance (concordance index 0.72 for all-cause mortality), improved Cox
      regression models including NPs (P < 0.001), and was the only biomarker also
      predicting non-cardiac death (hazard ratio 1.8 vs. 1.0). In the setting of low
      NPs, patients with high MR-proADM experienced non-cardiac death more often. Six
      month MR-proADM enhanced models including baseline MR-proADM (P < 0.001) for
      prediction of all-cause death (net reclassification index: 0.48, 95% confidence
      interval 0.19-0.78). CONCLUSION: MR-proADM was found to correlate with the global
      disease burden in HF and proved a potent prognostic indicator, capturing the risk
      for both cardiac and non-cardiac death. Serial MR-proADM measurements further
      enhanced risk assessment, thus facilitating substantial reclassification.

PMID- 28516505
TI  - Associations between nursing home performance and hospital 30-day readmissions
      for acute myocardial infarction, heart failure and pneumonia at the healthcare
      community level in the United States.
AB  - OBJECTIVES: To evaluate community-specific nursing home performance with
      community-specific hospital 30-day readmissions for Medicare patients discharged
      with acute myocardial infarction, heart failure or pneumonia. DESIGN: Cross
      sectional study using 2009-2012 hospital risk-standardised 30-day readmission
      data for Medicare fee-for-service patients hospitalised for all three conditions
      and nursing home performance data from the Centers for Medicare & Medicaid
      Services Five-Star Quality Rating System. SETTING: Medicare-certified nursing
      homes and acute care hospitals. PARTICIPANTS: 12,542 nursing homes and 3,039
      hospitals treating 30 or more Medicare fee-for-service patients for all three
      conditions across 2,032 hospital service areas in the United States.
      MEASUREMENTS: Community-specific hospital 30-day risk-standardised readmission
      rates. Community-specific nursing home performance measures: health inspection,
      staffing, Registered Nurses and quality performance; and an aggregated
      performance score. Mixed-effects models evaluated associations between nursing
      home performance and hospital 30-day risk-standardised readmission rates for all
      three conditions. RESULTS: The relationship between community-specific hospital
      risk-standardised readmission rates and community-specific overall nursing home
      performance was statistically significant for all three conditions. Increasing
      nursing home performance by one star resulted in decreases of 0.29% point (95%
      CI: 0.12-0.47), 0.78% point (95% CI: 0.60-0.95) and 0.46% point (95% CI: 0.33
      0.59) of risk-standardised readmission rates for AMI, HF and pneumonia,
      respectively. Among the specific measures, higher performance in nursing home
      overall staffing and Registered Nurse staffing measures was statistically
      significantly associated with lower hospital readmission rates for all three
      conditions. Notable geographic variation in the community-specific nursing home
      performance was observed. CONCLUSION: Community-specific nursing home performance
      is associated with community-specific hospital 30-day readmission rates for
      Medicare fee-for-service patients for acute myocardial infarction, heart failure
      or pneumonia. IMPLICATIONS FOR PRACTICE: Coordinated care between hospitals and
      nursing homes is essential to reduce readmissions. Nursing homes can improve
      performance and reduce readmissions by increasing registered nursing homes.
      Further, communities can work together to create cross-continuum care teams
      comprised of hospitals, nursing homes, patients and their families, and other
      community-based service providers to reduce unplanned readmissions.

PMID- 28516506
TI  - Diversity of Chemical Bonding and Oxidation States in MS4 Molecules of Group 8
      Elements.
AB  - The geometric and electronic ground-state structures of 30 isomers of six MS4
      molecules (M=Group 8 metals Fe, Ru, Os, Hs, Sm, and Pu) have been studied by
      using quantum-chemical density functional theory and correlated wavefunction
      approaches. The MS4 species were compared to analogous MO4 species recently
      investigated (W. Huang, W.-H. Xu, W. H. E. Schwarz, J. Li, Inorg. Chem. 2016, 55,
      4616). A metal oxidation state (MOS) with a high value of eight appeared in the
      low-spin singlet Td geometric species (Os,Hs)S4 and (Ru,Os,Hs)O4 , whereas a low
      MOS of two appeared in the high-spin septet D2d species Fe(S2 )2 and (slightly
      excited) metastable Fe(O2 )2 . The ground states of all other molecules had
      intermediate MOS values, with S2- , S22- , S21- (and O2- , O1- , O22- , O21- )
      ligands bonded by ionic, covalent, and correlative contributions. The known
      tendencies toward lower MOS on going from oxides to sulfides, from Hs to Os to
      Ru, and from Pu to Sm, and the specific behavior of Fe, were found to arise from
      the different atomic orbital energies and radii of the (n-1)p core and (n-1)d and
      (n-2)f valence shells of the metal atoms in row n of the periodic table. The
      comparative results of the electronic and geometric structures of the MO4 and MS4
      species provides insight into the periodicity of oxidation states and bonding.

PMID- 28516507
TI  - An All-Plastic Field-Effect Nanofluidic Diode Gated by a Conducting Polymer
      Layer.
AB  - The design of an all-plastic field-effect nanofluidic diode is proposed, which
      allows precise nanofluidic operations to be performed. The fabrication process
      involves the chemical synthesis of a conductive poly(3,4-ethylenedioxythiophene)
      (PEDOT) layer over a previously fabricated solid-state nanopore. The conducting
      layer acts as gate electrode by changing its electrochemical state upon the
      application of different voltages, ultimately changing the surface charge of the
      nanopore. A PEDOT-based nanopore is able to discriminate the ionic species
      passing through it in a quantitative and qualitative manner, as PEDOT nanopores
      display three well-defined voltage-controlled transport regimes: cation
      rectifying, non-rectifying, and anion rectifying regimes. This work illustrates
      the potential and versatility of PEDOT as a key enabler to achieve
      electrochemically addressable solid-state nanopores. The synergism arising from
      the combination of highly functional conducting polymers and the remarkable
      physical characteristics of asymmetric nanopores is believed to offer a promising
      framework to explore new design concepts in nanofluidic devices.

PMID- 28516508
TI  - Near-infrared photodynamic inactivation of S. pneumoniae and its interaction with
      RAW 264.7 macrophages.
AB  - Pneumonia is the main cause of children mortality worldwide, and its major
      treatment obstacle stems from the microorganisms increasing development of
      resistance to several antibiotics. Photodynamic therapy has been presenting, for
      the last decades, promising results for some subtypes of cancer and infections.
      In this work we aimed to develop a safe and efficient in vitro protocol for
      photodynamic inactivation of Streptococcus pneumoniae, one of the most commonly
      found bacteria in pneumonia cases, using two near-infrared light sources and
      indocyanine green, a FDA approved dye. Photodynamic inactivation experiments with
      bacteria alone allowed to determine the best parameters for microbial
      inactivation. Cytotoxicity assays with RAW 264.7 macrophages evaluated the safety
      of the PDI. To determine if the photodynamic inactivation had a positive or
      negative effect on the natural killing action of macrophages, we selected and
      tested fewer indocyanine green concentrations and 10 J/cm2 on macrophage-S.
      pneumoniae co-cultures. We concluded that ICG has potential as a photosensitizer
      for near-infrared photodynamic inactivation of S. pneumoniae, producing minimum
      negative impact on RAW 264.7 macrophages and having a positive interaction with
      the immune cell's microbicidal action.

PMID- 28516510
TI  - Proteomic analysis of Lupinus angustifolius (var. Zeus and Bojar) and Lupinus
      luteus (var. Lord and Parys) seed proteins and their hydrolysates.
AB  - BACKGROUND: Proteins enzymatic digestion is a very complex process, during which
      some components are degraded, whereas others remain in an unchanged form.
      Moreover, enzymatic hydrolysis is one of the most popular methods used to reduce
      the allergenicity of food proteins. In the present study, the efficiency of
      enzymatic hydrolysis of lupin seed proteins was assessed by proteomic analysis as
      performed by two-dimensional gel electrophoresis (2-DE) coupled with mass
      spectrometry identification. Two digestion systems were used: oriented digestion
      carried out by trypsin and model in vitro digestion mimicking the conditions
      present in the gastrointestinal tract. RESULTS: The comparisons of 2-DE maps of
      proteins isolated form different lupin seed species revealed that the differences
      in proteins expression were observed mainly in the central parts of gels (i.e. in
      the molecular weight range from 20 to 70 kDa, and the pH range 5-7). In total, 27
      differentially expressed proteins spots were successfully identified by mass
      spectrometry analysis. An important reduction in the number of proteins spots on
      2-DE maps was observed when trypsin and the in vitro digestion model were
      applied. The protein spot insensitive to digestion in both hydrolysis systems was
      identified as beta-conglutin. CONCLUSIONS: The results of the present study
      provide insight into the nature of the digestion process that may take place
      after lupin seed protein intake and highlight the important fact that some of the
      proteins are insensitive to digestive enzyme activity. Moreover, evaluation of
      digestion activity of trypsin towards lupin seed proteins may be used for the
      development of specific processes with respect to hypoallergenic food production.
      (c) 2017 Society of Chemical Industry.

PMID- 28516511
TI  - An Electrochemically Treated BiVO4 Photoanode for Efficient Photoelectrochemical
      Water Splitting.
AB  - BiVO4 films with (040) facet grown vertically on fluorine doped SnO2 (FTO) glass
      substrates are prepared by a seed-assisted hydrothermal method. A simple
      electrochemical treatment process drastically enhances the photocatalytic
      activity of BiVO4 , exhibiting a remarkable photocurrent density of 2.5 mA cm-2
      at 1.23 V vs. reversible hydrogen electrode (RHE) under AM 1.5 G illumination,
      which is approximately 10-fold higher than that of the pristine photoanode.
      Loading cobalt borate (CoBi) as cocatalyst, the photocurrent density of the BiVO4
      photoanode can be further improved to 3.2 mA cm-2 , delivering an applied bias
      photon-to-current efficiency (ABPE) of 1.1 %. Systematic studies reveal that
      crystal facet orientation also synergistically boosts both charge separation and
      transfer efficiencies, resulting in remarkably enhanced photocurrent densities.
      These findings provide a facile and effective approach for the development of
      efficient photoelectrodes for photoelectrochemical water splitting.

PMID- 28516509
TI  - The incidence and predictors of depressive and anxiety symptoms in older adults
      with vision impairment: a longitudinal prospective cohort study.
AB  - PURPOSE: Depression and anxiety are highly prevalent in older adults with vision
      impairment. Because symptoms of depression and anxiety appear to fluctuate, it is
      important to identify patients who are at risk of developing these symptoms for
      early diagnosis and treatment. Therefore, the aim of this study was to determine
      the incidence of subthreshold depression and anxiety, and to investigate
      predictors of developing symptoms of depression and anxiety in older adults with
      vision impairment who had no subthreshold depression or anxiety at baseline.
      METHODS: A longitudinal prospective cohort study with a follow-up of 24 months in
      540 older adults with vision impairment (mean age 75 years, 56% female, 48%
      macular degeneration, 15% glaucoma) from outpatient low-vision rehabilitation
      organisations was performed. The cumulative incidences of subthreshold depression
      and anxiety were calculated and linear mixed models with maximum likelihood
      estimation were used to determine two prediction models. Main outcome measures
      were: fluctuations in (i) depressive symptoms (Center for Epidemiologic Studies
      Depression Scale, CES-D) and (ii) anxiety symptoms (Hospital Anxiety and
      Depression Scale-Anxiety subscale, HADS-A). RESULTS: The annual cumulative
      incidences of subthreshold depression and anxiety were 21.3% (95% Confidence
      Interval (CI) 18.7-23.9%) and 9.5% (95% CI 7.4-11.6%), respectively. Risk factors
      for developing depressive symptoms were: living alone, having just enough money
      to cover expenses, having macular degeneration, having problems with adaptation
      to vision loss, reduced health related quality of life, and experiencing symptoms
      of anxiety. For developing anxiety symptoms, a relatively younger age,
      experiencing symptoms of depression, not living alone and experiencing hindrance
      at work proved to be risk factors. CONCLUSIONS: This study shows that the
      incidence of subthreshold depression and anxiety in older adults with vision
      impairment is twice as high compared with older adults in general and confirms
      that depression and anxiety symptoms fluctuate over time. It is of great
      importance that low vision rehabilitation staff monitor older adults with vision
      impairment who are most vulnerable for developing these symptoms, based on the
      risk factors that were found in this study, to be able to offer early
      interventions to prevent and treat mental health problems in this population.

PMID- 28516512
TI  - Defective alpha2 antiplasmin cross-linking and thrombus stability in a case of
      acquired factor XIII deficiency.
AB  - Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition
      that is often misdiagnosed or missed completely. A 72-year-old woman presented
      with symptoms of major unprovoked bleeding but routine coagulation screening
      tests and platelet count were normal. Low activated FXIII (FXIIIa) activity
      levels and abnormal urea clot stability led to diagnosis of acquired FXIII
      deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml
      indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose
      of FXIII concentrate and immunosuppression with prednisolone induced remission. A
      subsequent relapse was treated with combined prednisolone and Rituximab resulting
      in a prolonged, ongoing remission. Here we analyse the mechanisms underlying this
      idiopathic case of acquired FXIII deficiency. Prospective analysis of patient
      plasma revealed minimal FXIIIa activity and antigen in presentation and relapse
      samples. Thrombi formed from these samples lysed rapidly and showed an absence of
      cross-linked alpha2 AP. Western blotting revealed the presence of FXIII-B,
      indicating only FXIII-A and FXIII-A2 B2 were affected. FXIII activity and antigen
      levels normalised on remission. Our data suggest the presence of inhibitor
      induced clearance of FXIII from plasma. As a consequence, reduced thrombus
      stability was evident due to defective alpha2 AP cross-linking, thereby
      explaining symptoms of excessive bleeding.

PMID- 28516513
TI  - Evaluating an educational intervention to alleviate distress amongst men with
      newly diagnosed prostate cancer and their partners.
AB  - OBJECTIVE: To determine whether an education session alleviates distress for both
      patients with prostate cancer and their partners; and whether their partner's
      attendance at the session; and disease, treatment, and sociodemographic
      characteristics affect changes in distress levels. PATIENTS, SUBJECTS AND
      METHODS: We identified men with untreated prostate cancer at the Vancouver
      Prostate Centre between February 2015 and March 2016 who agreed to attend our
      education session. The session consisted of a didactic presentation covering the
      biology of prostate cancer, treatment options, and side-effects, followed by a
      private joint session with a urologist and radiation oncologist. We assessed
      distress using the Distress Thermometer (DT) and compared pre- and post-session
      distress, and change in distress between patients and partners using matched and
      unmatched t-tests, respectively. We also assessed pre-session anxiety using the
      seven-item Generalised Anxiety Disorder measure, and decisional certainty using
      the Decisional Conflict Scale. RESULTS: In all, 71 patients and 48 partners
      participated in the study. Attending the session led to a significant reduction
      in the median DT score for patients (4.0-3.0, P < 0.01) and partners (5.0-4.0, P
      = 0.02). Partners reported higher distress both before and after the session (4.9
      vs 3.8, P = 0.03 pre-session and 4.2 vs 3.2, P = 0.03 post-session). The presence
      of a partner at the session did not affect patients' pre- or post-session
      distress or the success of the session at alleviating distress. Sociodemographic
      and clinical characteristics had little effect on distress levels. CONCLUSIONS:
      An interdisciplinary education session is equally effective at alleviating
      distress for both patients with prostate cancer and their female partners.

PMID- 28516514
TI  - Single-incision totally extraperitoneal inguinal hernia repair is feasible and
      safe in patients on antithrombotic therapy: A single-center experience of 92
      procedures.
AB  - INTRODUCTION: The aim of this study was to evaluate the feasibility and safety of
      SILS for totally extraperitoneal inguinal hernia repair for patients on
      antithrombotic therapy. METHODS: A total of 365 patients who underwent SILS for
      totally extraperitoneal inguinal hernia repair between January 2011 and November
      2015 were analyzed retrospectively. Antithrombotic drugs were stopped
      preoperatively, and bridging intravenous heparin therapy was given according to
      the operative risk of each patient. Data on the patients' characteristics and
      perioperative outcomes were collected from their medical records. RESULTS: Ninety
      two patients (25%, 92/365) were treated with antithrombotic drugs preoperatively.
      The mean operative times for unilateral and bilateral hernia repairs were 96 min
      and 94 min (P = 0.5), respectively, in the antithrombotic therapy group and 140
      min and 130 min (P = 0.2), respectively, in the control group. Bleeding volume
      was minimal in all patients. There was no significant difference in the
      conversion rate. The mean postoperative hospital stay was 2.5 days in the
      antithrombotic therapy group and 2.1 days in the control group (P = 0.1).
      Postoperative complications were seen in 16% (15/92) of patients in the
      antithrombotic therapy group and in 11% (29/273) of patients in the control group
      (P = 0.2). Pulmonary embolism was seen in one patient (0.4%, 1/273) in the
      control group. CONCLUSIONS: SILS for totally extraperitoneal inguinal hernia
      repair with bridging heparin therapy can be performed safely for patients on
      antithrombotic therapy.

PMID- 28516515
TI  - Interaction of lincRNA ROR and p53/miR-145 correlates with lung cancer stem cell
      signatures.
AB  - ROR is one of large intergenic non-coding RNAs (lincRNAs) and acts as a strong
      negative regulator of p53 and a sponge for miR-145 to regulate diverse cancer
      progression. However, the interaction of ROR, p53 and miR-145 in lung cancer and
      its correlation with lung cancer stem cell (LCSC) signatures were not fully
      understood. Here, qRT-PCR analysis revealed that p53 and ROR were upregulated
      while miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and
      LCSCs compared to their paired adjacent normal tissues and lung cancer cells
      (LCCs). Besides, high p53 level, low miR-145 level, and high ROR level were
      associated with poor prognosis in NSCLC. Then, we found that silencing ROR failed
      to change p53 mRNA level but promoted p53 protein level, suggesting a
      posttranscriptional regulation mechanism involved in si-ROR-mediated promotion of
      p53. While silencing p53 moderately downregulated ROR. Additionally, silencing
      ROR or p53 upregulated miR-145. However, silencing both ROR and p53 failed to
      make obvious change to miR-145 mRNA level and p53 protein level. And
      interestingly, miR-145 negatively regulated Oct4 and Sox2. We also found that
      silencing ROR and (or) p53 suppressed in vitro cell proliferation, migration and
      invasion in LCSCs and LCCs. And suppression of endogenous ROR reduced the in vivo
      tumor growth and metastasis of LCSCs. Our study demonstrated that ROR and p53/miR
      145 correlated with prognosis in NSCLC as well as cell proliferation, migration,
      invasion, and tumorigenicity of LCSCs, shedding new light on novel therapeutic
      options in lung cancer. This article is protected by copyright. All rights
      reserved.

PMID- 28516516
TI  - Toward Long-Term Stable and Efficient Large-Area Organic Solar Cells.
AB  - Here, we report that long-term stable and efficient organic solar cells (OSCs)
      can be obtained through the following strategies: i) combination of rapid-drying
      blade-coating deposition with an appropriate thermal annealing treatment to
      obtain an optimized morphology of the active layer; ii) insertion of interfacial
      layers to optimize the interfacial properties. The resulting devices based on
      poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']dithiophene-2,6
      diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4-b]thiophene-2-carboxylate-2,6
      diyl)] (PBDTTT-EFT):[6,6]-phenyl C71 butyric acid methyl ester (PC71 BM) blend as
      the active layer exhibits a power conversion efficiency (PCE) up to 9.57 %, which
      represents the highest efficiency ever reported for blade-coated OSCs.
      Importantly, the conventional structure devices based on poly(3-hexylthiophene)
      (P3HT):phenyl-C61 -butyric acid methyl ester (PCBM) blend can retain
      approximately 65 % of their initial PCE for almost 2 years under operating
      conditions, which is the best result ever reported for long-term stable OSCs
      under operational conditions. More encouragingly, long-term stable large-area
      OSCs (active area=216 cm2 ) based on P3HT:PCBM blend are also demonstrated. Our
      findings represent an important step toward the development of large-area OSCs
      with high performance and long-term stability.

PMID- 28516520
TI  - Poster - Thur Eve - 04: Online review of beam output and profile constancy using
      statistical process control.
AB  - The objective of this work was to create a comprehensive online tool to evaluate
      and review the performance of quality assurance measurements that assess beam
      output and profile constancy as soon as they are acquired using statistical
      process control. As part of routine quality assurance: output, flatness and
      symmetry measurements are acquired daily and weekly with DQA3 and the Matrix and
      symmetry and flatness are acquired on a monthly basis with Profiler2. An
      individuals control chart and a moving range control chart was plotted for each
      set of data. Upper and lower control limits were calculated using measurements
      acquired during a several month period when the linear accelerators were
      operating optimally. The existing action levels, established according to TG142
      and CAPCA guidelines were compared with the calculated statistical control
      limits. Tighter tolerance limits were recommended for output, symmetry and
      flatness Matrix measurements and DQA3 flatness measurements.

PMID- 28516518
TI  - meta-C-H Arylation and Alkylation of Benzylsulfonamide Enabled by a
      Palladium(II)/Isoquinoline Catalyst.
AB  - Palladium(II)-catalyzed meta-C-H arylation and alkylation of benzylsulfonamide
      using 2-carbomethoxynorbornene (NBE-CO2 Me) as a transient mediator are realized
      by using a newly developed electron-deficient directing group and isoquinoline as
      a ligand. This protocol features broad substrate scope and excellent functional
      group tolerance. The meta-substituted benyzlsulfonamides can be readily
      transformed into sodium sulfonates, sulfonate esters, and sulfonamides, as well
      as styrenes by Julia-type olefination. The unique impact of the isoquinoline
      ligand underscores the importance of subtle matching between ligands and the
      directing groups.

PMID- 28516519
TI  - Exercise training in Diastolic Heart Failure (Ex-DHF): rationale and design of a
      multicentre, prospective, randomized, controlled, parallel group trial.
AB  - Heart failure with preserved ejection fraction (HFpEF) is a common disease with
      high incidence and increasing prevalence. Patients suffer from functional
      limitation, poor health-related quality of life, and reduced prognosis. A pilot
      study in a smaller group of HFpEF patients showed that structured, supervised
      exercise training (ET) improves maximal exercise capacity, diastolic function,
      and physical quality of life. However, the long-term effects of ET on patient
      related outcomes remain unclear in HFpEF. The primary objective of the Exercise
      training in Diastolic Heart Failure (Ex-DHF) trial is to investigate whether a 12
      month supervised ET can improve a clinically meaningful composite outcome score
      in HFpEF patients. Components of the outcome score are all-cause mortality,
      hospitalizations, NYHA functional class, global self-rated health, maximal
      exercise capacity, and diastolic function. After undergoing baseline assessments
      to determine whether ET can be performed safely, 320 patients at 11 trial sites
      with stable HFpEF are randomized 1:1 to supervised ET in addition to usual care
      or to usual care alone. Patients randomized to ET perform supervised
      endurance/resistance ET (3 times/week at a certified training centre) for 12
      months. At baseline and during follow-up, anthropometry, echocardiography,
      cardiopulmonary exercise testing, and health-related quality of life evaluation
      are performed. Blood samples are collected to examine various biomarkers. Overall
      physical activity, training sessions, and adherence are monitored and documented
      throughout the study using patient diaries, heart rate monitors, and
      accelerometers. The Ex-DHF trial is the first multicentre trial to assess the
      long-term effects of a supervised ET programme on different outcome measures in
      patients with HFpEF.

PMID- 28516521
TI  - Poster - Thur Eve - 14: The effect of fluence and detector size on image quality
      in multi-projection compton scatter tomography.
AB  - PURPOSE: To assess how radiation dose and size of energy sensitive detectors
      affects image quality in multi-projection Compton scatter tomography. METHODS AND
      MATERIALS: A Compton scatter tomography system was simulated in Maltab. The
      system consists of a point source generated x-ray fan beam and energy sensitive
      photon counting detectors, placed along a line with the source outside the
      periphery of the primary beam. Single scattered photons from a low contrast
      phantom simulating breast tissues were simulated. Simulation parameters are dose
      limited and closely matched to typical breast CT. Poisson distributed noise was
      added to simulate quantum noise. RESULTS: We have successfully reconstructed
      electron density images in a clinical fan-beam breast CT system, in the presence
      of noise. The reconstruction illustrates accurate spatial alignment of the
      structures of interest in the phantom. The increase in MSE due to noise was ~11%.
      The optimal detector size of 2 * 2 mm2 is a trade off between the increased
      noise, that is present when smaller detector sizes are used, and the blurring of
      the image that occurs as larger detectors are employed. CONCLUSIONS: For breast
      CT dose of 4-12 mGy, the optimal detector size for a Compton scatter
      reconstruction using 360 projections and 1000 eV energy resolution was found to
      be 2 * 2 mm2 . The ability to visualize large low contrast (9%) and small (2 mm
      diameter) high contrast objects was demonstrated.

PMID- 28516522
TI  - Sci-Thur PM: YIS - 07: Monte Carlo simulations to obtain several parameters
      required for electron beam dosimetry.
AB  - When current dosimetry protocols were written, electron beam data were limited
      and had uncertainties that were unacceptable for reference dosimetry. Protocols
      for high-energy reference dosimetry are currently being updated leading to
      considerable interest in accurate electron beam data. To this end, Monte Carlo
      simulations using the EGSnrc user-code egs_chamber are performed to extract
      relevant data for reference beam dosimetry. Calculations of the absorbed dose to
      water and the absorbed dose to the gas in realistic ion chamber models are
      performed as a function of depth in water for cobalt-60 and high-energy electron
      beams between 4 and 22 MeV. These calculations are used to extract several of the
      parameters required for electron beam dosimetry - the beam quality specifier, R50
      , beam quality conversion factors, kQ and kR50 , the electron quality conversion
      factor, k'R50 , the photon-electron conversion factor, kecal , and ion chamber
      perturbation factors, PQ . The method used has the advantage that many important
      parameters can be extracted as a function of depth instead of determination at
      only the reference depth as has typically been done. Results obtained here are in
      good agreement with measured and other calculated results. The photon-electron
      conversion factors obtained for a Farmer-type NE2571 and plane-parallel PTW Roos,
      IBA NACP-02 and Exradin A11 chambers are 0.903, 0.896, 0.894 and 0.906,
      respectively. These typically differ by less than 0.7% from the contentious TG-51
      values but have much smaller systematic uncertainties. These results are valuable
      for reference dosimetry of high-energy electron beams.

PMID- 28516523
TI  - Poster - Thur Eve - 07: CNSC Update: "What's New in Class II".
AB  - The Accelerators and Class II Facilities Division (ACFD) of the Canadian Nuclear
      Safety Commission (CNSC), is responsible for the oversight of radiotherapy
      facilities containing Class II prescribed equipment in Canada. This poster will
      highlight a number of new initiatives that the CNSC has implemented recently that
      have an impact on radiotherapy facility licensees. The presentation will discuss
      the recent policy decision to regulate particle accelerators of above 1 MeV.
      Challenges and progress with respect to the implementation of the policy will be
      presented. Other initiatives which will be described include: * The new ACFD
      webspace on the CNSC website, with direct links to relevant information on
      licensing, compliance and Class II prescribed equipment * The improved structure
      of the Appendix of Licence Documents that is part of every Class II licence *
      Updated licence application guides * Changes to Annual Compliance reporting
      requirements and progress on the ACR-Online initiative * Changes to some
      regulatory expectations related to medical accelerator facilities * Consolidation
      of Class II facility licences The poster will also include other initiatives that
      may be of particular interest to COMP membership.

PMID- 28516524
TI  - Sci-Thur AM: Planning - 07: A fast and accurate source model for energy and
      intensity modulated electron beams.
AB  - The purpose of this study is to develop a highly accurate and fast method for
      calculating electron beam dose distributions in Modulated Electron Radiation
      Therapy (MERT). An algorithm has been developed for creating phase-space files at
      the exit of a linear accelerator for any arbitrary intensity and energy electron
      beam without the need of full Monte Carlo simulations. The model assigns each
      particle to one of the 3 following sources: primary, secondary collimator and
      electron collimator scatter. The primary component is derived by fast MC
      transport in air. The scatter components are derived by the use of MC pre
      calculated leaf kernels. Each kernel includes the fluence distribution, energy
      distribution and scatter probability of generating an electron from a leaf. The
      original position is sampled from tunable Gaussian or uniform distributions. The
      direction is estimated by geometrical means. According to the projection of the
      direction a particle is rejected if it is expected to suffer a leaf-hit. A leaf
      hit counter is used to calculate the output of scatter particles based on the pre
      calculated scatter probabilities. To account for multiple coulomb scattering in
      air a MC-corrected version of the Fermi-Eyges scattering theory was implemented.
      Depth and profile dose distributions were derived for the largest and smallest
      square field sizes, as well as for irregular and off-axis fields. The model
      agreed with full MC dose distributions within 3 % in all cases. Output at the
      depth of maximum dose exhibited discrepancies less than 2.6 % in all cases. The
      model was 16-22 times faster in generating a phase-space file than a full MC
      simulation with the BEAMnrc code.

PMID- 28516526
TI  - Poster - Thur Eve - 01: Development of simple and fast EBT2 film calibration
      procedure using PDD table.
AB  - Standard calibration procedure for EBT films is laborious and time-consuming. The
      objective of this work was to develop a simple and fast approach of EBT2 film
      calibration using PDD tables. EBT2 sheet is cut into 3 stripes of 5*25.5cm2 . The
      strips were exposed to dose of 600, 200 and 70cGy at dmax each while placed
      horizontally in the middle of a 30*30*30cm3 solid water phantom. Varian 21EX 6MV
      10*10cm2 beam was used with the gantry rotated to 90 degrees  and SSD of 100cm to
      the phantom surface. After at least 24 hours, the films were digitized with
      flatbed scanner (Epson10000XL), according to a modified ISP scanning protocol.
      All images were analysed using an in-house Matlab code and ImageJ software. The
      net-optical densities against depths in the solid phantom were calibrated using
      PDD tables measured with ionization chamber for same machine. For verification,
      another calibration curve was generated for the same film batch following the
      same calibration protocol. Seven pieces of films were exposed to known doses and
      these doses were reconstructed using two derived calibration curves. The proposed
      approach was 3.6 times faster than the standard considering the number of films
      used in each methods, 3 stripes compared to11 pieces. The mean relative dose
      difference calculated for these films using the PDD calibration and the standard
      methods was 1.0+/-1.2% and 0.5+/-2.2% with maximum relative differences of 3.0%
      and 4.7% respectively. Our results show that PDD calibration approach is much
      easier, faster and predicts dose more reproducibly and accurately than the
      standard approach.

PMID- 28516527
TI  - Poster - Thur Eve - 11: A realistic respiratory trace generator and its
      application to respiratory management techniques.
AB  - Respiratory motion complicates radiotherapy treatment of thoracic and abdominal
      tumours. Simplified respiratory motions such as sinusoidal and single patient
      traces are often used to determine the impact of motion on respiratory management
      techniques in radiotherapy. Such simplifications only accurately model a small
      portion of patients, as most patients exhibit variability and irregularity beyond
      these models. We have preformed a comprehensive analysis of respiratory motion
      and developed a software tool that allows for explicit inclusion of variability.
      We utilize our realistic respiratory generator to customize respiratory traces to
      test the robustness of the estimate of internal gross target volumes (IGTV) by
      4DCT and CBCT. We confirmed that good agreement is found between 4DCT and CBCT
      for regular breathing motion. When amplitude variability was introduced the
      accuracy of the estimate slightly, but the absolute differences were still < 3 mm
      for both modalities. Poor agreement was shown with the addition of baseline
      drifts. Both modalities were found to underestimate the IGTV by as much as 30%
      for 4DCT and 25% for CBCT. Both large and small drifts deteriorated the estimate
      accuracy. The respiratory trace generator was advantageous for examining the
      difference between 4DCT and CBCT IGTV estimation under variable motions. It
      provided useful implementation abilities to test specific attributes of
      respiratory motion and detected issues that were not seen with the regular motion
      studies. This is just one example of how the respiratory trace generator can be
      utilized to test applications of respiratory management techniques.

PMID- 28516528
TI  - Sci-Thur AM: Planning - 11: The impact of distributed calculation framework
      settings on plan calculation time.
AB  - Some treatment planning system can divide a treatment plan calculation into
      multiple threads and allow both local and network computing resources to perform
      the calculation concurrently, which significantly reduces the calculation time
      for a calculation-demanding planning such as Volumetric Modulated Arc Therapy
      (VMAT) or electron Monte Carlo (eMC). This study tested in Eclipse (Varian,
      V10.0.39) the impact of Distributed Calculation Framework (DCF, V10.0.0.757)
      settings on calculation time in a planning environment that consists of 20
      workstations with 8 core processors and 16GB RAMs installed on most of them. It
      is found that for an arc plan increasing the control point field parallelization
      factor reduces the total calculation time at beginning but lengthens the total
      calculation time after a certain level as a result of data sending time increase.
      Further increasing the factor may cause a serious net work traffic or even
      failure of a calculation. For an eMC plan the calculation time decreases
      monotonously with the increase of Monte carlo field parallelization factor, and
      the data sending time is insignificant compared to the calculation time.
      Increasing the local servant numbers reduces the data sending time but raises the
      calculation time for arc and eMC plans. The calculation time increment is more
      and more significant with the increase of local servants. The optimal DCF setting
      for a facility depends on the total number of calculation workstations available,
      the hardware configuration of the workstations, and the data transfer rate of the
      network. No conflict of interest exists in the study.

PMID- 28516529
TI  - Sci-Thur AM: Planning - 04: Evaluation of the fluence complexity, solution
      quality, and run efficiency produced by five fluence parameterizations
      implemented in PARETO multiobjective radiotherapy treatment planning software.
AB  - PURPOSE: PARETO (Pareto-Aware Radiotherapy Evolutionary Treatment Optimization)
      is a novel multiobjective treatment planning system that performs beam
      orientation and fluence optimization simultaneously using an advanced
      evolutionary algorithm. In order to reduce the number of parameters involved in
      this enormous search space, we present several methods for modeling the beam
      fluence. The parameterizations are compared using innovative tools that evaluate
      fluence complexity, solution quality, and run efficiency. METHODS: A PARETO run
      is performed using the basic weight (BW), linear gradient (LG), cosine transform
      (CT), beam group (BG), and isodose-projection (IP) methods for applying fluence
      modulation over the projection of the Planning Target Volume in the beam's-eye
      view plane. The solutions of each run are non-dominated with respect to other
      trial solutions encountered during the run. However, to compare the solution
      quality of independent runs, each run competes against every other run in a round
      robin fashion. Score is assigned based on the fraction of solutions that survive
      when a tournament selection operator is applied to the solutions of the two
      competitors. To compare fluence complexity, a modulation index, fractal
      dimension, and image gradient entropy are calculated for the fluence maps of each
      optimal plan. RESULTS: We have found that the LG method results in superior
      solution quality for a spine phantom, lung patient, and cauda equina patient. The
      BG method produces solutions with the highest degree of fluence complexity. Most
      methods result in comparable run times. CONCLUSION: The LG method produces
      superior solution quality using a moderate degree of fluence modulation.

PMID- 28516530
TI  - Measurement and Detection of Radiation.

PMID- 28516533
TI  - Poster - Thur Eve - 03: LDR to HDR: RADPOS applications in brachytherapy.
AB  - The RADPOS in vivo dosimetry system combines an electromagnetic positioning
      sensor and either one or five MOSFET dosimeters. The feasibility of using the
      system for quality control has been explored for a range of radiotherapy
      treatment techniques including most recently transperineal interstitial permanent
      prostate brachytherapy and high dose rate (HDR) treatments. Dose and position
      information was collected by a RADPOS array detector inside a Foley catheter
      within patients' urethra during permanent seed implantation. Ten patients were
      studied, and average displacement during implantation was Deltar = (1.4-5.1) mm,
      with movements up to 9.7 mm due to the removal of the transrectal ultrasound
      probe. Maximum integral dose in the prostatic urethra ranged from 110-195 Gy, and
      it was found that the dose can change up to 63 cGy (62.0%) depending on whether
      the rectal probe is in place. For HDR, a RADPOS detector was first calibrated
      with an Ir-192 source. A treatment was then simulated using a total of 50 dwell
      positions in 5 catheters in an acrylic phantom. Dwell positions ranged from 1 to
      10 cm away from the RADPOS detector and dose was measured for each source
      position. An average calibration coefficient of 0.74+/-0.11 cGy/mV was calculated
      for the detector and the average absolute difference between measured values and
      expected dose was 0.7+/-5.4 cGy (5+/-20%). The demonstrated accuracy of RADPOS
      dose measurements along with its ability to simultaneously measure displacement
      makes it a powerful tool for brachytherapy treatments, where high dose gradients
      can present unique in vivo dosimetry challenges.

PMID- 28516535
TI  - Sci-Thur PM: YIS - 06: Effect of the k-space sampling pattern on the MTF of
      compressed sensing MRSI.
AB  - Compressed Sensing MRSI (CS-MRSI) offers the ability to accelerate MRSI sequences
      while suffering minimal artifacts compared to conventional fast MRSI techniques.
      CS-MRSI exploits the inherent sparsity of MRSI images and incoherent artifacts of
      pseudo-random sub-Nyquist sampling of k-space combined with non-linear
      reconstruction to produces MRSI images. CS-MRSI can be used as an acceleration
      tool to decrease the scan time while maintaining acceptable spatial definition or
      to enable the acquisition of higher resolution scans while minimizing the
      associated time penalty. In this work we adopt the compressed sensing technique
      to accelerate a clinically relevant 2-D point resolved spectroscopy sequence.
      However, the process of weighing the cost and benefit of applying such a fast
      imaging technique is complicated due to the unique non-linear nature of the
      reconstruction process and has largely relied on qualitative assessments.
      Moreover, pseudo-random sub-Nyquist sampling of k-space can have unwanted effects
      on the modulation transfer function. In this work we set out to quantify the loss
      in image quality associated with CS-MRSI. We used simulations of a phantom based
      method to investigate the MTF behaviour of CS-MRSI with regard to different k
      space sampling patterns. As expected, the k-space sampling patterns tested were
      found to have a direct effect on the MTFs. Moreover, limiting the deviation of
      the resulting k-space sampling pattern from the prescribed probability
      distribution function had a positive effect on the MTF overall. Not only was low
      resolution response improved, but we also noticed an improvement of ~ 26% in
      resolution at 0.1 MTF.

PMID- 28516534
TI  - Poster - Thur Eve - 13: Quantifying specific absorption rate of shielded RF coils
      through electromagnetic simulations for 7-T MRI.
AB  - Ultra-high field MRI has many advantages such as increasing spatial resolution
      and exploiting contrast never before seen in-vivo. This contrast has been shown
      to be beneficial for many applications such as monitoring early and late effect
      to radiation therapy and transient changes during disease to name a few. However,
      at higher field strengths the RF wave, needed to for transmitting and receiving
      signal, approaches that of the head. This leads to constructive and
      deconstructive interference and a non -uniform flip angle over the volume being
      imaged. A transmit or transceive RF surface coil arrays is currently a method of
      choice to overcome this problem; however, mutual inductance between elements
      poses a significant challenge for the designer. A method to decouple elements in
      such an array is by using circumferential shielding; however, the potential
      benefits and/or disadvantages have not been investigated. This abstract primarily
      focuses on understanding power deposition - measured through Specific Absorption
      Rate - in the sample using circumferentially shielded RF coils. Various
      geometries of circumferentially shielded coils are explored to determine the
      behaviour of shield width and its effect on required transmit power and power
      deposition to the sample. Our results indicate that there is an optimization on
      shield width depending on the imaging depth. Additionally, the circumferential
      shield focuses the field more than unshielded coils, meaning that slight SAR may
      even be lower for circumferential shielded RF coils in array.

PMID- 28516536
TI  - Poster - Thur Eve - 17: Control point analysis comparison of three different
      treatment planning and delivery complexity levels using a commercial three
      dimensional diode array.
AB  - PURPOSE: To use Control Point Analysis (Sun Nuclear Corporation, Melbourne,
      Florida, USA) to analyze and compare delivered VMAT plans for three different
      treatment planning complexity levels. METHODS: Nineteen patients were chosen and
      fully anonymized for the purpose of this study. Ten SBRT, six H&N, one breast and
      two prostate VMAT plans were generated on Pinnacle3 and delivered on a Varian
      LINAC. The delivered dose was measured using ArcCHECKTM. Each plan was analyzed
      using SNC Patient 6 and Control Point Analysis. Gamma passing percentage was used
      to assess the differences between the measured and planned dose distributions and
      to assess the role of various control point binning scenarios. RESULTS: The
      prostate cases reported the highest gamma passing percentages for SNC Patient 6
      (99.3%-99.5%,3%/3mm) and Control Point Analysis (99.1--99.3%,3%/3mm). The mean
      percentage of passing control point sectors for the prostate cases increased from
      48.9+/-3.1% for individual control points to 69.5 +/- 3.9% for 5 control points
      binned together to 100+/-0% for 10 control points binned together. Over all,
      there was a trend in the percentage of sectors passing gamma analysis increasing
      with the increase of the number of control points binned together in one sector
      for both passing criteria considered (48.9+/-3.1% for individual control points
      to 69.5+/-3.9% for 5 control points binned together in one sector to 100+/-0% for
      10 control points binned together in one sector for the prostate). CONCLUSION:
      The delivery accuracy per control point depends on the MU/control point (SBRT)
      and the plan degree of modulation (H&N).

PMID- 28516537
TI  - Sci-Thur AM: Planning - 06: Planning target volume margin suitability in lung
      stereotactic body radiation therapy: A preliminary evaluation using cone-beam
      computed tomography.
AB  - Stereotactic body radiation therapy (SBRT) requires precise delivery of radiation
      to the target; intra- and inter-fraction lung tumour motion may adversely impact
      local tumour control. The purpose of this study was to retrospectively evaluate
      the impact of planning target volume (PTV) margin size on the coverage of the
      internal target volume (ITV) as localized in pre- and post-treatment cone-beam
      computed tomography (CBCT) images. Data from two patients undergoing SBRT were
      evaluated. For planning, free-breathing and 4DCT scans were performed, and used
      to contour the ITV. A 5mm margin was added to create the PTV. During treatment,
      14 CBCTs were collected pre- and post-beam delivery. A data set comprising the
      average 4DCT intensities where available and treatment planning CT intensities
      for voxels that were beyond the field of view of the 4DCT was constructed.
      Registration of the combined planning image to each CBCT was performed using a
      deformable image registration algorithm. The transformations aligning the
      combined planning image with the CBCTs were applied to the planning ITV to obtain
      the treatment ITVs. For each CBCT, the fraction of treatment ITV within the PTV
      was determined using Boolean logic. This was repeated for various PTV margins
      ranging from 0 to 10 mm at 1mm intervals. The 3 and 5 mm PTV margins covered 95.1
      +/- 5.9% and 99.0 +/- 2.0% of the ITV, respectively. Analysis of additional
      patients will be performed to confirm these preliminary results, which reinforce
      the use of a 5mm PTV margin for lung SBRT.

PMID- 28516538
TI  - Sci-Thur PM: YIS - 10: A new optically encoded single-fiber plastic scintillation
      detector for multi-point radiation dosimetry.
AB  - PURPOSE: To develop a new multi-point plastic scintillation detector (mPSD) that
      allows for simultaneous dose measurements at multiple points and uses a single
      optical guide. MATERIALS AND METHODS: Two different prototypes were built. A two
      point mPSD was built and light discrimination was based on the use of multiple
      color filters at the outputs of a network of optical fiber splitters. Light
      intensity was measured by an EMCCD camera. For the three-point mPSD, the light
      discrimination setup was replaced by a low-noise spectrometer. Depth-dose and
      profiles measurements were obtained on a 6 MV photon beam with the mPSDs inside a
      water phantom. An ion chamber was also used for comparison purpose. Finally, the
      three-point mPSD was tested under an Ir-192 high-dose-rate (HDR) brachytherapy
      dose delivery and compared to the treatment planning system. RESULTS: A good
      agreement was found between the measured and expected dose for both mPSDs. The
      average relative differences to the ion chamber measurement for the two-point
      mPSD were of (2.4 +/- 1.6)% and (1.3 +/- 0.8)%. For the three-point mPSD, these
      differences were of (2.3+/-1.1)%, (1.6+/-0.4)% and (0.32+/-0.19)%. The latter
      mPSD was shown very versatile, being able to measure dose from HDR brachytherapy
      with an average accuracy of (2.3+/-1.0)% per catheter. CONCLUSIONS: The practical
      feasibility of mPSDs using a single optical guide has been demonstrated under
      irradiation from a 6 MV photon beam and an Ir-192 HDR brachytherapy source. Their
      application for pre-treatment quality assurance and in vivo dosimetry will be
      various.

PMID- 28516539
TI  - Poster - Thur Eve - 10: Long term stability of VMAT quality assurance parameters
      using an EPID.
AB  - The rapidly growing use of volumetric modulated arc therapy (VMAT) treatments in
      radiation therapy calls for a quantitative, automated, and reliable quality
      assurance (QA) procedure that can be used routinely in the clinical setting. In
      this work, we present a series VMAT QA procedures used to assess dynamic multi
      leaf collimator (MLC) positional accuracy, variable dose-rate accuracy, and MLC
      leaf speed accuracy. The QA procedures were performed using amorphous silicon
      electronic portal imaging devices (EPID) to determine the long term stability of
      the measured parameters on two Varian linear accelerators. The measurements were
      repeated weekly on both linear accelerators for a period of three months and the
      EPID images were analyzed using custom Matlab software. The results of the picket
      fence tests indicate that MLC leaf positions can be identified to within 0.11 mm
      and 0.15 mm for static gantry delivery and VMAT delivery respectively. In
      addition, the dose-rate, gantry speed and MLC leaf speed tests both show very
      good stability over the measurement period. The measurements thus far, suggest
      that a number of the dosimetry tests may be suitable for quarterly QA for Varian
      iX and Trilogy linacs. However, additional measurements are required to confirm
      the frequency with which each test is required for safe and reliable VMAT
      delivery at our centre.

PMID- 28516540
TI  - Sci-Thur AM: Planning - 10: Improved dosimetric accuracy for patient specific
      quality assurance using a dual-detector measurement method for cyberknife output
      factors.
AB  - The measurement of output factors for small fields is challenging and can lead to
      large dose errors in patient treatments if corrections for detector size and
      scatter from high-Z material are not applied. Due to its high spatial resolution
      and near tissue equivalence, GAFCHROMIC(r) film potentially provides a correction
      free measure of output factors but it can be challenging to obtain high quality
      dosimetric results using this film. We propose minimizing errors in the clinical
      determination of small field output factors by employing diode measurements with
      Monte-Carlo generated corrections for small fields <=10 mm diameter and using
      small volume ion chambers for apertures >10 mm diameter with independent
      validation using radiochromic film. We performed patient specific quality
      assurance (QA) measurements for 9 patients using GAFCHROMIC(r) film and an A16
      small volume ion chamber in a head-shaped phantom, employing this hybrid dual
      detector method for relative output factor measurements within the Multiplan
      treatment planning system. Our results suggest that consistent output factors can
      be determined using this method with experimental verification using
      GAFCHROMIC(r) film dosimetry. For the patient specific QA using film, we achieve
      good dosimetric agreement (<2sigma) of the measured and calculated average dose
      for pixels within the 80% isodose line. For patient specific QA using the micro
      ion chamber, we get good agreement (<3%) for cone sizes greater than 5 mm. The
      differences observed for the 5 mm cone plans are consistent with a 1 mm radial
      setup uncertainty for patient positioning using the Cyberknife system.

PMID- 28516541
TI  - Sci-Thur AM: Planning - 03: Extensive patient specific QA for field junction
      regions for craniospinal irradiation with Jagged-Junction IMRT approach without
      beam edge matching for field junctions.
AB  - PURPOSE: Jagged-Junction IMRT was developed for craniospinal irradiation. An
      extensive QA was performed for the field junction regions. METHODS AND MATERIALS:
      The Jagged-Junction IMRT plan employed three field sets, each with unique
      isocentres (Iso1,2,3). Fields from adjacent sets were overlapped and the dose was
      smoothly integrated inside the overlapped junction. The delivered dose in the
      junction regions were verified with film and ion chamber measurements on
      phantoms. An anthropomorphic-wax phantom was created for verifying the cranio
      spinal junction. For measuring at the spinal-spinal junction, a solid water
      phantom was used. The influence of beam mismatching due to setup and mechanical
      inaccuracy was investigated by shifting all the fields from Iso1 and Iso3
      superiorly and inferiorly by 3 mm and at the same time keeping all the fields
      from Iso2 without any shift. RESULTS: The patient-averaged difference between the
      measured dose with ion chamber and planned dose in the cranio-spinal junction is
      0.34 % +/- 0.40% and in the spinal-spinal junction this difference is 0.03% +/-
      0.71%. The dose profile comparison shows that measured and planned dose profiles
      match well to each other over a junction region. The patient-averaged dose
      difference discrepancy between the film measurement and the planned is 1.1% +/-
      1.3% at the cranio-spinal junction and -0.14% +/- 1.8% at the spinal junction.
      CONCLUSIONS: Jagged-Junction IMRT planning provided smooth dose coverage to the
      target in the field junction region. The junction dose for the Jagged-Junction
      IMRT plan is not sensitive to the setup error during the treatment.

PMID- 28516542
TI  - Sci-Thur PM: YIS - 02: A validated approach for clinical linacs to accurately
      determine the photon spectra and the incident electron energy.
AB  - In clinical photon beams, independent determination of the photon spectra and the
      incident electron energy is useful for beam (re)commissioning and for detector
      response modelling. In this study, an approach is developed for that purpose, and
      validated on a research linac whose photon spectra and electron beams are
      directly and independently known. In this approach, an optimized combination of
      transmission curves is measured using multiple attenuators and detectors to
      maximize energy differentiation. For validation, transmission measurements are
      made for 8 beams from 10-30 MV, with bremsstrahlung targets from Be to Pb. A
      protocol is established to account for many influence quantities including linac
      drifts (2%), polarity (6%), ion recombination (0.2%), leakage (0.3%), room
      scatter (0.8%), non-ideal attenuation (1.5%), attenuator mass thickness (4%), and
      photonuclear effect (5.6%). The experimental accuracy on the smallest signals is
      0.4%. EGSnrc is upgraded to model photonuclear attenuation (without tracking
      secondary particles), and then used to model the full experiment. For direct
      transmission comparisons, the agreement is 2%. This allows for an estimate of
      0.5% on the upper limit of photon cross section uncertainties, which is much
      better than the current estimate of 1-2%. The unfolded spectra agree with the
      benchmark ones within 4.5%. The incident electron energy is accurate within 5%,
      with 95% confidence. The overall improvement over the commonly used methods is a
      factor of 3. This transmission study is the first to independently determine the
      incident electron energy, and to recognize the significant role of the
      photonuclear effect at higher energies.

PMID- 28516544
TI  - Poster - Thur Eve - 12: Dosimetric manifestation of harmonic mode imaging for
      seed implant brachytherapy.
AB  - PURPOSE: To demonstrate the dosimetric effects of observer variability in
      defining the prostate and critical organs, using Tissue Harmonic (H) ultrasound
      imaging mode for permanent seed implant brachytherapy. METHODS: Images were
      acquired using a B -K medical 8848 probe with Brightness (B) and H mode for ten
      prostate brachytherapy patients. The prostate, rectum and urethra were contoured
      independently by five observers. The clinically used treatment plans based on B
      mode imaging fulfilling the dosimetric criteria were applied on these contours.
      Dosimetric parameters (prostate: D90, V100 and V200; rectum: V100; urethra: V140,
      V150 and V160) were computed using SPOT PROTM planning system. Interobserver
      variability in dosimetric parameters was tested using standard deviations as
      percentages of means. RESULTS: Two-factor analysis of variances showed
      significant (p<0.05) interobserver variability in all dosimetric parameters for
      both modes. Interobserver agreement in dosimetric parameters improves in H mode
      due to improved interobserver consistency in contouring these organs on H mode
      images compared to B mode. There is no significant difference observed (paired
      student t test, p>0.05) in the mean values of dosimetric parameters in H and B
      mode for prostate and critical organs. CONCLUSIONS: H mode due to its better
      image quality helped to improve the interobserver agreement in contouring the
      prostate and critical organs and hence better interobserver consistency in all
      dosimetric parameter. Because the difference in the mean value of dosimetric
      parameters between two imaging modes is not statistically significant, H mode
      does not appear to offer any clinical advantages in terms of improving the
      dosimetric outcome.

PMID- 28516545
TI  - Sci-Thur PM: YIS - 05: Tomographic dosimetry using scintillating fibers and its
      application to 2D and 3D dosimetry.
AB  - PURPOSE: To present the proof of concept and the experimental validation of
      tomographic dosimetry (tomodosimetry), where a tomographic acquisition of the
      incident deposited dose is performed using long scintillating fibers. METHOD: 2D
      tomodosimetry: 50 long scintillating fibers were aligned on a 20cm diameter disk
      inside a 30cm diameter masonite phantom. 3D tomodosimetry: 128 long scintillating
      fibers of various orientation were simulated on the surface of two cylindrical
      regions of radius 7.5 and 3.75cm inside a 20cm diameter, 20cm long cylindrical
      phantom. In both case, the dose projections were acquire each 5 degrees over a
      180 degrees (2D) or 360 degrees (3D) rotation of the device, and the dose in each
      scintillating fiber plane was reconstructed using a total variation minimization
      reconstruction iterative algorithm at a resolution of 1*1mm2 . The 3D dose was
      obtained by interpolating between in each cylindrical plane in the 3D prototype.
      RESULTS: 3%/3mm gamma tests conducted in the isocentre plane for both
      configurations achieved a success rate of more than 99% of the dose pixels in the
      region over 50% of the maximum dose. Absolute dose differences in the high dose
      low gradient region of each scintillating fiber plane were on average below 1%
      for the 2D configuration and below 1.3% for the 3D configuration. CONCLUSIONS:
      This work illustrates the potential and capacity of scintillating fiber based 2D
      and 3D tomodosimeters. The presented methodology allows for millimeter resolution
      dosimetry in a whole 2D plane or 3D volumes in real-time using only a limited
      number of detectors.

PMID- 28516546
TI  - Poster - Thur Eve - 06: Comparison of an open source genetic algorithm to the
      commercially used IPSA for generation of seed distributions in LDR prostate
      brachytherapy.
AB  - In early stage prostate cancer, low dose rate (LDR) prostate brachytherapy is a
      favorable treatment modality, where small radioactive seeds are permanently
      implanted throughout the prostate. Treatment centres currently rely on a
      commercial optimization algorithm, IPSA, to generate seed distributions for
      treatment plans. However, commercial software does not allow the user access to
      the source code, thus reducing the flexibility for treatment planning and
      impeding any implementation of new and, perhaps, improved clinical techniques. An
      open source genetic algorithm (GA) has been encoded in MATLAB to generate seed
      distributions for a simplified prostate and urethra model. To assess the quality
      of the seed distributions created by the GA, both the GA and IPSA were used to
      generate seed distributions for two clinically relevant scenarios and the quality
      of the GA distributions relative to IPSA distributions and clinically accepted
      standards for seed distributions was investigated. The first clinically relevant
      scenario involved generating seed distributions for three different prostate
      volumes (19.2 cc, 32.4 cc, and 54.7 cc). The second scenario involved generating
      distributions for three separate seed activities (0.397 mCi, 0.455 mCi, and 0.5
      mCi). Both GA and IPSA met the clinically accepted criteria for the two
      scenarios, where distributions produced by the GA were comparable to IPSA in
      terms of full coverage of the prostate by the prescribed dose, and minimized dose
      to the urethra, which passed straight through the prostate. Further, the GA
      offered improved reduction of high dose regions (i.e hot spots) within the
      planned target volume.

PMID- 28516547
TI  - Poster - Thur Eve - 16: Four-dimensional x-ray computed tomography and
      hyperpolarized 3 He magnetic resonance imaging of gas distribution in lung
      cancer.
AB  - Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and
      static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver
      direct and regional measurements of lung function even in lung cancer patients in
      whom global lung function measurements are dominated by tumour burden. The
      purpose of this study was to directly compare quantitative measurements of gas
      distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small
      group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior
      to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation
      1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using
      a semi-automated segmentation algorithm to generate percent-ventilated volume
      (PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity
      volume. 4DCT pulmonary function maps were generated using deformable image
      registration of six expiratory phase images. The correspondence between identical
      tissue elements at inspiratory and expiratory phases was used to estimate
      regional gas distribution and PVV was quantified from these images. After
      accounting for differences in lung volumes between 3 He MRI (1.9+/-0.5L
      ipsilateral, 2.3+/-0.7 contralateral) and 4DCT (1.2+/-0.3L ipsilateral, 1.3+/
      0.4L contralateral) during image acquisition, there was no statistically
      significant difference in PVV between 3 He MRI (72+/-11% ipsilateral, 79+/-12%
      contralateral) and 4DCT (74+/-3% ipsilateral, 75+/-4% contralateral). Our results
      indicate quantitative agreement in the regional distribution of inhaled gas in
      both static and dynamic imaging methods. PVV may be considered as a regional
      surrogate measurement of lung function or ventilation.

PMID- 28516549
TI  - Sci-Thur PM: YIS - 09: Development of a graphite probe calorimeter for absolute
      clinical dosimetry: Numerical design optimization, prototyping and experimental
      proof-of-concept.
AB  - In this work, the feasibility of absolute dose to water measurements using a
      small-scale graphite probe calorimeter (GPC) in a clinical environment is
      established. A numerical design optimization study was conducted by simulating
      the heat transfer in the GPC resulting from irradiation using a finite element
      method software package. The choice of device shape, dimensions and materials was
      made to minimize the heat loss in the sensitive volume of the GPC. The resulting
      design, which incorporates a novel aerogel-based thermal insulator, was built in
      house. Absorbed dose to water measurements were made under standard conditions in
      a 6 MV 1000 MU/min photon beam and subsequently compared against TG-51 derived
      values. The average measured dose to water was 95.7 +/-1.4 cGy/100 MU, as
      compared to an expected value of 96.6 cGy/100 MU. The Monte Carlo-calculated
      graphite to water dose conversion factor was 1.099, while the derived heat loss
      correction factors varied between 1.005 and 1.013. The most significant sources
      of uncertainty were the repeatability (type A, 1.4%) and thermistor calibration
      (type B, 2.1%). The contribution of these factors to the overall uncertainty is
      expected to decrease significantly upon the implementation of active thermal
      stabilization provided by a temperature controller and direct electrical
      calibration, respectively. This work demonstrates the feasibility of using the
      GPC as a practical clinical absolute photon dosimeter and will serve as the basis
      for a miniaturized version applicable to small and composite fields.

PMID- 28516548
TI  - Sci-Thur AM: Planning - 05: Lung SBRT: Dosimetric accuracy of the Analytical
      Anisotropic Algorithm (AAA) for 6MV FFF RapidArc planning.
AB  - PURPOSE: Stereotactic Body Radiation Therapy (SBRT) requires the delivery of a
      high biologically effective dose in only a few fractions. These large doses per
      fraction can necessitate long treatment times. The Varian Truebeam is capable of
      RapidArc delivery and also has the optional Flattening Filter Free (FFF) modes
      which greatly increase the dose rate. We have commissioned the 6MV FFF beam (1400
      MU/min) for RapidArc lung SBRT, and verified heterogeneous dose calculations with
      Monte Carlo (MC). METHODS: The standard commissioning data was acquired for
      Varian's Analytical Anisotropic Algorithm (AAA) beam model. Measurements were
      acquired with the IBA Blue Phantom, using the CC13 and CC01 ion chambers and PTW
      diode. MLC-defined fields were also acquired for model verification. The
      Dosimetric Leaf Gap (DLG) was measured and then optimized using RapidArc lung
      SBRT plans, matching Eclipse with ion chamber measurements. Heterogeneous dose
      calculations were independently verified using MC. RESULTS: There were some
      discrepancies regarding leaf transmission and penumbra, but the AAA model was
      generally well within 2% and 2 mm. A nominal DLG value of 1.6 mm was chosen. A
      representative lung SBRT case utilizing FFF RapidArc was calculated with MC. For
      the high dose region, 99% matched Eclipse within 3% and 3 mm. The mean dose
      difference of the PTV was 0.7%. CONCLUSIONS: Although we have observed some minor
      infield discrepancies between the AAA and Monte Carlo calculations in
      heterogeneous media, the Eclipse AAA is reasonably accurate for complex FFF,
      RapidArc, SBRT lung planning.

PMID- 28516550
TI  - Poster - Thur Eve - 09: Novel radiation safety challenges of a brachytherapy
      redevelopment at the Credit Valley Hospital.
AB  - Carlo Fidani Peel Regional Cancer Center at the Credit Valley Site of the Credit
      Valley Hospital and Trillium Health Center is currently undergoing a
      redevelopment to build a brachytherapy suite and associated areas with a
      projected start date of April 2013. The new brachytherapy suite will be located
      in the PRCC, and is a redevelopment of office area into clinical space. The
      workload for the full brachytherapy program is expected to be 20 patients per
      week, in cervix, prostate, skin, lung and other sites. There were challenges for
      shielding due services in the slab to the renal clinic located above the
      redevelopment area. The presence of over 30 voids in the slab and upper walls
      made the solution to add shielding to the underside of the current slab
      unsuitable. To overcome this, a second ceiling built below the slab to allow for
      an uninterrupted shielding for the brachytherapy suite. The additional ceiling
      allows for a crawl space between slab and shielding allowing for servicing if
      needed for the drains from the renal clinic. The appropriate finalized shielding
      design is 69mm of lead brick supported by steel plate and steel beams. Final
      shielding for the walls is 690mm of concrete that allows public access to all
      hallways around the facility. The final design for the new brachytherapy site at
      the PRCC all services for the room are located within the shielding and all
      services for areas outside the room are located outside the shielding.

PMID- 28516552
TI  - Sci-Thur AM: Planning - 09: Assessing dynamic IMRT field modulation in prostate
      plans.
AB  - In a previous study, the variogram fractal dimension (FD) method was found to be
      very accurate at identifying planned head and neck IMRT fields that are overly
      modulated. In the current study, the authors used MATLAB(r) to develop FracMod, a
      graphical user interface (GUI) and variogram FD analysis tool to assess
      modulation complexity of dynamic IMRT fields designed for treatments of the
      prostate alone and prostate plus pelvic nodes. A set of 5 prostate plans (25
      fields) and 5 prostate plus pelvic node plans (35 fields) were used to choose FD
      cut-points that ensure no false positives (100% specificity) in distinguishing
      between moderate field modulation (typical modulation used clinically at the
      authors' institution) and high modulation. Field modulation was controlled by
      adjusting fluence smoothing parameters in the EclipseTM treatment planning
      system. The area under the curve (AUC) from receiver operating characteristic
      (ROC) analysis was used to quantitatively compare the ability of FD and the
      number of monitor units (MUs) for distinguishing between the moderate and high
      modulation fields. The variogram FD method gave AUCs of 0.96 (almost perfect
      classification) and 1.00 (perfect classification) for the prostate alone and the
      prostate plus pelvic node fields, respectively. The variogram FD method is an
      accurate metric; performing better than the number of MUs at identifying high
      modulation IMRT fields planned for the treatment of prostatic carcinoma. Hence,
      FracMod will enable Radiotherapy Physicists to easily and accurately quantify the
      degree of modulation of IMRT fields and adjust overly-modulated fields at the
      treatment planning stage.

PMID- 28516553
TI  - Sci-Thur AM: Planning - 02: Validation of XiO's eMC module using Gafchromic EBT3
      films and triple channel dosimetry.
AB  - The aim of this study is to validate the electron Monte Carlo module implemented
      in XiO, a treatment planning system commercialized by Elekta CMS inc. Two types
      of phantoms were investigated: homogeneous water phantoms with irregular surfaces
      and phantoms containing slab and 3D heterogeneities. The phantoms were CT
      scanned, and dose to water calculations were performed in the eMC module using 2
      *2 * 2 mm2 voxels and a mean relative statistical uncertainty of 0.5%.
      Concurrently, Gafchromic EBT3 film measurements were performed in the same
      phantoms. To obtain reliable absolute dose readings from the films, a new method
      using triple channel dosimetry in the Film QA Pro software was developed. The
      accuracy of the proposed method was determined empirically and an uncertainty of
      +/-1.5% was found over the range [75, 800] cGy. Dose comparisons between film and
      simulations were done using an in-house MATLAB program. XiO's eMC module provides
      accurate dose distributions in the presence of surface irregularities and slab
      heterogeneities for 12 MeV beams. In the presence of 3D heterogeneities, the
      percent dose difference comparisons highlighted the need to perform 3D gamma
      comparisons. In conclusion, the electron Monte Carlo module offered in the XiO
      treatment planning system is promising and could greatly improve the accuracy of
      clinical dose calculations. The validation of the software is ongoing, notably
      concerning more complex phantom geometries. Small field calculations, oblique
      incidences and cutout factors will also be investigated.

PMID- 28516554
TI  - Sci-Thur PM: YIS - 01: Inverse treatment planning for modulated electrons and
      mixed photon and electron radiotherapy.
AB  - Modulated electron radiotherapy (MERT) takes advantage of the low distal dose of
      electrons to reduce dose to healthy tissue. The dosimetric advantage of MERT is
      clear when compared against single-field electron irradiation where MERT
      demonstrates superior target homogeneity and sparing; however the dosimetric
      advantage is unclear when comparing MERT with photon intensity-modulated
      radiotherapy (IMRT) where MERT techniques struggle to match the IMRT target
      homogeneity but with less total energy delivered to healthy tissues. In an effort
      to improve dosimetric benefits of MERT, this study investigated an inverse
      planning technique for the creation of hybrid MERT-IMRT mixed beam radiotherapy
      (MBRT) plans. The optimization process decouples the photon and electron beamlets
      for combined modality optimization. The input to the optimization algorithm was a
      series of patient-specific 3D dose distributions for the corresponding electron
      and photon beamlets, while the output was a list of weights that satisfied the
      optimization constraints. A photon IMRT Eclipse (Varian, Palo Alto, CA) plan and
      a MERT plan were created for a patient-specific sarcoma irradiation. The MERT
      plan was competitive in its ability to reduce dose to organs at risk and total
      body dose; however, the plan suffered from poorer target conformity compared with
      the IMRT plan. The MBRT plan was created by adding two photon fields, divided
      into beamlets, to the electron beamlets of the MERT plan for reoptimization. The
      MBRT plan improved MERT target coverage with only minimal cost to healthy tissue
      dose. The MBRT plan provided clear dosimetric advantages over the IMRT and MERT
      plan.

PMID- 28516556
TI  - Erratum: "Enhanced dosimetry procedures and assessment for EBT2 radiochromic
      media" [Med. Phys. 39(4), pp. 2147-2155 (2012)].

PMID- 28516557
TI  - Sci-Thur PM: YIS - 04: Forcing lateral electron disequilibrium to spare lung
      tissue: A novel technique for SBRT of small lung tumours.
AB  - Stereotactic body radiation therapy(SBRT), a technique that uses tightly
      conformed Megavoltage(MV) x-ray fields, improves local control of lung cancer.
      However, small MV x-ray fields can cause lateral electron disequilibrium(LED),
      which reduces the dose within lung. These effects are difficult to predict and
      are presently a cause of alarm for the radiotherapy community. Previously, we
      developed The Relative Depth Dose Factor(RDDF), which is an indicator of the
      extent of LED (RDDF < 1). We propose a positive application of LED for lung
      sparing in SBRT: LED can be exploited to irradiate a small tumor while greatly
      reducing the dose in surrounding lung tissue. The Monte Carlo code, DOSXYZnrc,
      was employed to calculate dose within a cylindrical lung phantom. The phantom's
      diameter and height were set to 25 cm, and consisted of water and lung (density =
      0.25g/cm3 ) shells surrounding a small water tumor (volume = 0.8 cm3 ). Two 180
      degrees  6MV arcs were focused onto the tumor with field sizes of 1*1cm2
      (RDDF~0.5) and 3*3cm2 (RDDF~1). Analyzing dose results, the 1*1cm2 arc reduced
      dose within lung and water tissues by 70% and 80% compared to the 3*3cm2 arc.
      Although, central tumor dose was also reduced by 15% using the 1*1cm2 arc, these
      reductions can be offset by escalating the prescription dose appropriately. Using
      the RDDF as a guideline, it's possible to design a SBRT treatment plan that
      reduces lung dose while maintaining relatively high tumor dose levels. Clinical
      application requires an accurate dose algorithm and may lower SBRT dose-induced
      toxicity levels in patients.

PMID- 28516558
TI  - Poster - Thur Eve - 05: Safety systems and failure modes and effects analysis for
      a magnetic resonance image guided radiation therapy system.
AB  - INTRODUCTION: An online Magnetic Resonance guided Radiation Therapy (MRgRT)
      system is under development. The system is comprised of an MRI with the
      capability of travel between and into HDR brachytherapy and external beam
      radiation therapy vaults. The system will provide on-line MR images immediately
      prior to radiation therapy. The MR images will be registered to a planning image
      and used for image guidance. With the intention of system safety we have
      performed a failure modes and effects analysis. METHODS: A process tree of the
      facility function was developed. Using the process tree as well as an initial
      design of the facility as guidelines possible failure modes were identified, for
      each of these failure modes root causes were identified. For each possible
      failure the assignment of severity, detectability and occurrence scores was
      performed. Finally suggestions were developed to reduce the possibility of an
      event. RESULTS/DISCUSSION: The process tree consists of nine main inputs and each
      of these main inputs consisted of 5 - 10 sub inputs and tertiary inputs were also
      defined. The process tree ensures that the overall safety of the system has been
      considered. Several possible failure modes were identified and were relevant to
      the design, construction, commissioning and operating phases of the facility. The
      utility of the analysis can be seen in that it has spawned projects prior to
      installation and has lead to suggestions in the design of the facility.

PMID- 28516559
TI  - Poster - Thur Eve - 15: Production and assessment of astatine-211 for targeted
      alpha therapy.
AB  - Biologically-targeted alpha-particle radiation is the basis of new and promising
      treatments for eliminating disseminated micrometastases and the residual
      microscopic malignancies that remain after surgery or radiation therapy. The
      short-range alpha-particles are highly cytotoxic and capable of inactivating
      single, isolated cancer cells which may otherwise cause recurrence. Astatine-211
      is a promising alpha emitter for therapy; the 7.2 hour half-life of 211 At
      provides sufficient time for biological-targeting to take place. However, this
      radionuclide is in short supply and future treatment strategies still require
      extensive preclinical evaluation. The present work aims to develop technologies
      that (1) increase the world-wide availability of 211 At for clinical use, and (2)
      assess the risks of 211 At-based therapies by quantifying the activity
      distributions in animal models. At TRIUMF (Vancouver, BC), the feasibility of a
      novel generator system for 211 At is under investigation which would allow
      distribution of 211 At across Canada and internationally. Briefly, a longer-lived
      parent radionuclide of 211 At, radon-211, would be produced and allowed to decay
      in containment to yield 211 At in solution. Additionally, a supplementary study
      is underway in collaboration with the University of Washington to evaluate the
      sub-organ biodistributions of astatinated targeting biomolecules, with cell-level
      resolution. These measurements involve high resolution quantitative alpha
      particle imaging in thin tissue samples and can be done for a selection of
      applications (eg. lymphoma, metastatic prostate cancer, etc) using animal models.
      The planned alpha-camera measurements are primarily designed to predict and
      assess the risk of toxicity associated with 211 At-based therapies and aid in
      developing the future clinical applications.

PMID- 28516560
TI  - Sci-Thur PM: YIS - 08: The effect of copper conversion plates on low-Z target
      image quality.
AB  - Current generation electronic portal imaging devices (EPID) contain a 1.0 mm
      copper conversion plate to increase detection efficiency of a therapeutic
      megavoltage spectrum. When using these EPIDs for low-Z target imaging, the
      conversion plate largely attenuates the large populations of diagnostic energy
      photons, thereby decreasing the benefits of low-Z target imaging. In this work we
      measure directly the effect the variation in thickness of a copper conversion
      plate has on image quality in planar and cone beam computed tomography imaging.
      Monte Carlo modeling was used to quantify changes to the diagnostic spectrum and
      detector response for low-Z target beams generated with 2.35 and 7.00 MeV
      electrons incident on a carbon target. Planar contrast-to-noise ratio (CNR)
      measurements were made as a function of copper thickness. Cone beam computed
      tomography (CBCT) image CNR measurements were made as a function of dose both
      with and without the copper plate present in the EPID. The presence of copper in
      the EPID decreased the diagnostic photon population by up to 20% and suppressed
      the peak detector response at 60 kV by a factor of 6.4. Planar CNR was increased
      by a factor ranging from 1.4 to 4.0 with no copper present compared to 1.0 mm
      thickness. Increases in CBCT image CNR ranged from a factor of 1.3 to 2.1 with
      the copper plate removed. As a result of this we suggest that the copper
      conversion plate be removed from the EPID when used for low-Z target planar or
      CBCT imaging.

PMID- 28516561
TI  - Poster - Thur Eve - 08: A1SL ion chamber charged particle disequilibrium
      corrections for lung dose measurements using Monte Carlo.
AB  - An in house inhomogeneous insert for use with ArcCHECK TM was developed for dose
      calculation verification of Stereotactic Body Radiation Therapy (SBRT) lung
      plans. The inhomogeneous insert has various ion chamber inserts for different
      geometrical configurations (lung, soft tissue, bone, air). However, the insertion
      of an ion chamber in a low density medium perturbs the dose to that region by
      creating Charged Particle Disequilibrium (CPD), limiting the accuracy of ion
      chamber measurements. By simulating the ion chamber and phantom using Monte
      Carlo, a correction factor could be calculated and measured to verify the dose
      difference caused by CPD. BEAMnrc was used to generate a phase space input file
      for DOSXYZnrc with beam characteristics that matched clinical commissioning data.
      A model of the A1SL ion chamber geometry (shell, collector, stem, guard) was
      simulated in a simple water-lung-water slab phantom. Dose to the active area of
      the ion chamber was measured in several locations throughout the phantom. The
      active area of the ion chamber was replaced by the surrounding medium; i.e.,
      water or lung within the phantom, and the dose to the same voxels was calculated.
      The dose was measured on a Linac and the results agreed within 3% and confirmed
      that the presence of the ion chamber in low density lung perturbs the dose
      measured in the field by over 31%.

PMID- 28516562
TI  - Sci-Thur AM: Planning - 08: Validation of a commercial Monte Carlo code used for
      stereotactic radiosurgery and stereotactic body radiation therapy.
AB  - Our project consisted of validating the BrainLab iPlan Monte Carlo algorithm,
      used in conjunction with the stereotactic radiosurgery (SRS) mode of the Varian
      Novalis TX linear accelerator, for clinical use. Our approach was to "benchmark"
      the iPlan algorithm by comparing dose distributions with those obtained using a
      BEAMnrc model of the Novalis SRS mode. The BEAMnrc model was obtained by
      modifying an existing accelerator model to include the SRS flattening filter and
      source characteristics of the Novalis TX, and by reprogramming a component module
      to model the high definition 120-leaf multi-leaf collimator. The free parameters
      of interleaf air gap and leaf density were adjusted by matching to interleaf
      leakage profiles measured with EBT2 film. The BEAMnrc model was used to perform
      comparisons of depth dose curves and planar distributions for fields in
      homogeneous and heterogeneous slab phantoms between both MC codes and film. The
      source parameters of electron beam energy, size and angular spread were
      determined to be 6.6 MeV, 0.7 mm and 0.8 mm (cross and in-plane), and 1.27
      degrees , respectively. Comparisons between iPlan and EGSnrc MC codes show
      agreement within 2% for PDD curves, and a high pass rate (>98%) on gamma analysis
      (3%/3mm) for planar distributions, when the scored quantity is dose to medium.
      Discrepancies between both MC codes and film measurements were seen near bone
      inhomogeneities, where the film trend agrees somewhat with iPlan MC reporting
      dose-to-water. Further work is being performed to understand these differences
      and how film is used to measure dose near bone.

PMID- 28516563
TI  - Reply to "Comment on the 'Report of AAPM TG 204: Size-specific dose estimates
      (SSDE) in pediatric and adult body CT examinations'" [AAPM Report 204, 2011].

PMID- 28516564
TI  - Poster - Thur Eve - 02: Regulatory oversight of the robotic radiosurgery
      facilities.
AB  - Following a recent review of the Class II Nuclear Facilities and Prescribed
      Equipment Regulations and regulatory oversight of particle accelerators, the
      Canadian Nuclear Safety Commission (CNSC) has changed its policy concerning the
      regulation of particle accelerators. In November 2011, the CNSC began to exercise
      its regulatory authority with respect to all particle accelerators operating at a
      beam energy of 1 (one) MeV or greater. The CNSC already licences and inspects
      particle accelerators capable of operating at or above 10 MeV. The decision to
      now include low energy particle accelerators (i.e., those operating at or above 1
      MeV) ensures adequate, uniform and consistent regulatory oversight for all Class
      II accelerators. The CNSC expects these facilities to comply with CNSC
      requirements by December 2013. Besides conventional linear accelerators of lower
      energy (6 MeV or below) typically found in cancer clinics, two types of equipment
      now fall under the CNSC's regulatory oversight as a result of the above change:
      robotic radiosurgery and tomotherapy equipment and facilities. A number of
      clinics in Canada already operates these types of equipment and facilities. The
      safety aspects of radiosurgery equipment differ slightly from those for
      conventional linear accelerators. This poster aims to present an approach taken
      by the CNSC to regulate robotic radiosurgery equipment and facilities. The
      presentation will explain how to meet regulatory requirements of the Class II
      Nuclear Facilities and Prescribed Equipment Regulations by licensees operating or
      planning to acquire these types of equipment and facilities.

PMID- 28516565
TI  - Sci-Thur AM: Planning - 01: Experimental and Monte Carlo verification of Acuros
      XB calculations near low and high density heterogeneities.
AB  - The purpose of this study was to examine the accuracy of AcurosXB and AAA
      algorithms near low and high density heterogeneities of different densities using
      EBT2 film, MOSFET detector "MOSkin" and Monte Carlo calculations using
      BEAMnrc/DOSXYZnrc. Three different interfaces were used that included a solid
      water phantom with 2*2*30cm3 rectangular air gap, rectangular steel insert, and a
      slab of water embedded between two slabs of lung material. 6MV photon beam with
      field size of 10*10cm2 was used for the first two geometries and a 3*3cm2 -field
      was used for the third. Percentage Depth Doses were measured and calculated at
      the beam central axis. Calculation voxel of 0.1*0.1*0.1cm3 was used by all three
      algorithms. For all configurations, AcurosXB and AAA agreed to within +/-1.3%
      with MC before the inhomogeneity. The PDD measurements using MOSkin and EBT2 in
      water, apart from 0.2cm layer near heterogeneity, agreed with the MC within +/
      2.2%. Within 0.1cm before the water-air interface AcurosXB and AAA overestimated
      the dose by 4.7% and 1.6%, respectively. Whereas, in the 0.1cm beyond the air
      water interface, AcurosXB and AAA overestimated the dose by 2.4% and 16.2%
      respectively. In the 0.1cm before the water-steel interface, AcurosXB
      overestimated the dose by 4.7% and AAA underestimated the dose by 9.5%; beyond
      the steel-water interface AcurosXB and AAA overestimated the dose by 3.6% and
      7.7% respectively. For the lung phantom configuration, AcurosXB and AAA were in
      agreement with MC within 2% throughout the phantom. These results demonstrate
      improved performance of AcurosXB as compared to AAA in considered conditions.

PMID- 28516566
TI  - Sci-Thur AM: Planning - 12: Comparative study of SBRT lung dose calculation using
      Eclipse and Monte Carlo.
AB  - Stereotactic Body Radiation Therapy (SBRT) is an option for early stage non-small
      cell lung cancer treatment. In SBRT treatment, high biological effective dose is
      delivered to the patient within a small number of fractions. High level of
      confidence in accuracy is required in the entire treatment procedure, from
      patient setup, tumour delineation, treatment simulation and planning, to the
      final dose delivery. SBRT lung treatment utilizes small fields that are incident
      on large tissue inhomogeneities within the patient. It is difficult for
      commercially available treatment planning systems (TPS) to model the lack of
      charged particle equilibrium and the dose near tissue-lung interfaces accurately.
      The Monte Carlo (MC) technique calculates the dose distribution from the first
      principles thereby providing a feasible tool for verifying the dose distribution
      computed from TPS. In this study, we compared the SBRT dose distribution between
      Eclipse 8.9 and BEAMnrc/DOSXYZnrc for both conformal and RapidArc plans.
      Calculation results for five clinical SBRT conformal lung plans were compared.
      Eclipse and MC results for each plan showed good agreement in dose received by
      organs at risk. MC simulation predicted uniformly hotter or similar PTV coverage
      for three cases with tumor either small or attached to the chest wall. When tumor
      is inside lung and at relatively medium to larger size for SBRT, MC predicted
      lower PTV coverage. The variation in dose coverage may depend on the tumour size
      and its position within the lung. Dose comparison for RapidArc plans shows
      similar dependence.

PMID- 28516568
TI  - Sci-Thur PM: YIS - 03: Comparing 4D-VMAT, Gated-VMAT and 3D-VMAT in SBRT
      treatment of lung cancer.
AB  - PURPOSE: To evaluate the treatment plan qualities of 4D-VMAT, gated-VMAT and 3D
      VMAT in the treatment of non-small cell lung cancer (NSCLC) in stereotactic body
      radiation therapy (SBRT). METHODS: 4D-VMAT is a motion compensation strategy that
      aims to exploit relative target and OAR motion to increase OAR sparing over 3D
      VMAT without the long treatment times associated with gated-VMAT. The 4D-VMAT
      algorithm incorporates the entire patient respiratory cycle and 4D-CT in the
      optimization process. Resulting treatment plans synchronize the delivery of each
      MLC aperture to a specific phase of the target motion. Using software developed
      in MatlabTM, SBRT treatment plans for 4D-VMAT, gated-VMAT and 3D-VMAT were
      generated on 3 patients with NSCLC. Tumour motion ranged from 1.4-3.4 cm. The
      fractionation scheme was 48Gy in 4 fractions with the GTV receiving 100% of the
      prescribed dose. For gated-VMAT, the treatment window constrained residual tumour
      motion to 3 mm or less corresponding to duty cycles of 40-60%. In 3D-VMAT, the
      ITV was generated by merging the GTV from all phases. A b-spline transformation
      model was used to register the 4D-CT images and DVHs were calculated from total
      dose accumulated on the max expiration phase. RESULTS AND CONCLUSION: For the
      majority of OARs, gated-VMAT provided the greatest radiation sparing but
      significantly extended treatment times (25-35 gantry interruptions/arc). For 3D
      VMAT, only 2 patients had clinically acceptable plans that met all the strict
      dose limits. OAR sparing in 4D-VMAT was comparable to gated-VMAT but with
      significantly improved delivery efficiency.

PMID- 28516569
TI  - STAT4 expression and activation is increased during mitosis in vitro and in vivo
      in skin- and mucosa-derived cell types: implications in neoplastic and
      inflammatory skin diseases.
AB  - BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4)
      is a transcription factor known to convey signals from interleukin-12,
      interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation
      of dendritic cells, T-helper cell differentiation and production of interferon
      gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS:
      Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is
      distributed throughout the cytoplasm during this stage of the cell cycle, whilst
      phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment.
      This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human
      keratinocytes and in other cell types. This is also present in vivo in cells
      undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma.
      Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA
      interference results in a delay in progression of mitosis and leads to a
      reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that
      STAT4 plays a role in enabling the normal and timely division of cells undergoing
      mitosis.

PMID- 28516570
TI  - Proposal of size-based surgical indication criteria for liver hemangioma based on
      a nationwide survey in Japan.
AB  - BACKGROUND: Surgical indications for liver hemangioma remain unclear. METHODS: Of
      510 patients undergoing surgical resection for liver hemangioma in 118 Japanese
      centers between 1998 and 2012, abdominal symptoms, diagnostic accuracy, and
      surgical outcomes were analyzed to propose size-based surgical indications.
      Patients were classified into four groups based on tumor size: Group A <=5 cm (n
      = 122, 24%), Group B 5-10 cm (n = 164, 32%), Group C 10-15 cm (n = 124, 24%), and
      Group D >15 cm (n = 100, 20%). RESULTS: Hemangiomas in Group A were most
      frequently diagnosed as malignant tumors (43.5%) due to the absence of typical
      imaging findings and with highest incidence of positive HBV (15.7%). Diagnostic
      accuracy was 98.4% in Groups B to D. Liver failure after hepatectomy was higher
      in Group D than in Groups A to C (3.0% vs. 0.5%, P = 0.02). Only one operative
      death was observed (0.2%) in Group D. CONCLUSIONS: In patients with <=5 cm
      hemangioma, surgical resection can be indicated when a malignant tumor cannot be
      ruled out. However, surgery for 5-10 cm asymptomatic hemangiomas should be
      limited. Experienced hepatic surgeons should conduct hepatectomy for tumors >15
      cm to avoid serious morbidity or mortality.

PMID- 28516622
TI  - Abstracts of the XVII GISMAD Congress, Milan, Italy, 9-11 March 2017.

PMID- 28516572
TI  - Identification of ageing biomarkers in human dermis biopsies by thermal analysis
      (DSC) combined with Fourier transform infrared spectroscopy (FTIR/ATR).
AB  - BACKGROUND/PURPOSE: The purpose of this clinical study was to identify suitable
      biomarkers for a better understanding of the molecular and organizational changes
      in human dermis during intrinsic and extrinsic ageing. METHODS: Sun-exposed and
      non-exposed skin biopsies were collected from twenty-eight women devised in two
      groups (20-30 and >=60 years old). The hydric organization and thermal
      transitions were determined by Differential Scanning Calorimetry (DSC). Fourier
      Transform Infrared spectroscopy (FTIR) was used to identify the absorption bands
      of the dermis and to quantify the different absorbance ratio. RESULTS: The
      amounts of total, freezable and unfreezable water were determined. A significant
      increasing amount of freezable water is evidenced in sun-exposed area skin of
      aged group compared with young group (P=.0126). Another significant effect of
      extrinsic ageing (P=.0489) is the drastic decrease of fibrillary collagen, the
      main protein component of dermis. The only significant effect of intrinsic ageing
      (P=.0184) is an increase of the heat-stable fraction of collagens in dermis.
      CONCLUSION: DSC and FTIR are well-suited techniques to characterize human skin,
      giving accurate results with a high reproducibility. The combination of these
      techniques is useful for a better understanding of human skin modifications with
      intrinsic and extrinsic ageing.

PMID- 28516571
TI  - FSOCA-induced switchable footpad skin optical clearing window for blood flow and
      cell imaging in vivo.
AB  - The mouse footpad for its feature of hairlessness provides an available window
      for imaging vascular and cellular structure and function in vivo. Unfortunately,
      the strong scattering of its skin limits the penetration of light and reduces the
      imaging contrast and depth. Herein, an innovative footpad skin optical clearing
      agent (FSOCA) was developed to make the footpad skin transparent quickly by
      topical application. The results demonstrate that FSOCA treatment not only
      allowed the cutaneous blood vessels and blood flow distribution to be monitored
      by laser speckle contrast imaging technique with higher contrast, but also
      permitted the fluorescent cells to be imaged by laser scanning confocal
      microscopy with higher fluorescence signal intensity and larger imaging depth. In
      addition, the physiological saline-treatment could make the footpad skin recover
      to the initial turbid status, and reclearing would not induce any adverse effects
      on the distributions and morphologies of blood vessels and cells, which
      demonstrated a safe and switchable window for biomedical imaging. This switchable
      footpad skin optical clearing window will be significant for studying blood flow
      dynamics and cellular immune function in vivo in some vascular and immunological
      diseases. Picture: Repeated cell imaging in vivo before (a) and after (b) FSOCA
      treatment. (c) Merged images of 4 h (cyan border) or 72 h (magenta border) over 0
      h. (d) Zoom of ROI in 4 h (yellow rectangle) or 72 h (red rectangle).

PMID- 28516623
TI  - Sci-Sat AM: Brachy - 05: Comprehensive web-based QA in radiation oncology.
AB  - Innovation/Impact: We describe the web-based QA infrastructure under development
      and in use within our paperless radiation oncology clinic. Our framework
      comprises a centralized web-server that facilitates simultaneous and seamless
      access to multiple databases within the clinic. All activities, including
      treatment planning, patient appointments and machine quality control/maintenance,
      are accessible via a single internal webpage with various software tools and
      metrics employed for QA and monitoring. We believe that our framework is
      representative of the direction in which modern radiation oncology departments
      are moving; namely paperless operation with centralized data access for patient
      specific QA and statistical process control.

PMID- 28516624
TI  - Sci-Fri PM: Delivery - 10: Megavoltage x-ray imaging detector based on cerenkov
      effect.
AB  - A Monte Carlo simulation was used to study imaging and dosimetric characteristics
      of a novel design of a megavoltage (MV) x-ray imaging detector. The proposed
      detector consists of a matrix of optical fibers aligned with the incident x-rays
      and coupled to an active matrix flat-panel imager (AMFPI) for image readout. The
      new design relies on Cerenkov effect for MV x-ray imaging and is named CPID (for
      Cerenkov Portal Imaging Device). When MV x-rays are incident on CPID, they
      interact within the volume of the detector primarily via Compton effect and pair
      production, resulting in electrons and positrons. From these charged particles,
      those with sufficient energy, trigger production of optical light via Cerenkov
      effect. The light that is generated in the optical fibre cores within the
      acceptance angle of the fibers is guided towards the AMFPI. Properties, such as
      detection efficiency, modulation transfer function, zero frequency detective
      quantum efficiency (DQE), and energy response of the detector, have been
      investigated. It has been shown that the proposed detector can have a zero
      frequency DQE more than an order of magnitude higher than that of current
      electronic portal imaging device (EPID) systems and yet a spatial resolution
      comparable to that of video-based EPIDs. In additional the proposed detector is
      less sensitive to scattered x-rays than current EPIDs.

PMID- 28516625
TI  - Sci-Sat AM: Brachy - 09: Permanent seed re-implantation using image guidance for
      composite dose planning.
AB  - Treatment outcome has been associated with dosimetric implant quality assessed in
      a postplan. Uncertainties during the implant and in the period before postplan
      evaluation lead to dosimetric deviations from the original treatment plan. The
      observed range of postplan results can include patients with dosimetry below
      recommended levels. Further treatment options may be considered to boost the
      delivered dose and a second seed implant is one way to accomplish this. This work
      describes the development of a procedure to plan and deliver a second seed
      implant and an evaluation of the dosimetric improvement. A patient with a post
      plan D90 of 124 Gy was offered a second seed implant 21 weeks after the initial
      implant. A total dose of 163 Gy was prescribed due to radiobiological
      considerations for the time between implants. A volume study was performed 2
      weeks before the implant and variable angle images of the seeds from the first
      implant were obtained to reconstruct the original seed coordinates. The second
      implant was planned considering the total composite physical dose distribution by
      forward planning additional seeds onto the original implant coordinates. The
      additional seeds were manually added to a new plan on the volume study images at
      the planned coordinates and delivered as a typical preplanned implant. Post-plan
      evaluation four weeks after the second implant showed a D90 of 177 Gy and a V100
      of 92.7%. These results demonstrate the effective use of a second seed implant
      with image guided composite planning to improve dosimetric implant quality.

PMID- 28516626
TI  - Poster - Thur Eve - 73: Prediction of risks of cardiac mortality and secondary
      cancers after radiotherapy for Hodgkin's lymphoma, non-Hodgkin's lymphoma, and
      breast cancer.
AB  - PURPOSE: To predict the risks of late, radiation-induced effects for young
      patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), or breast
      cancer (BC) if treated with intensity modulated proton therapy (IMPT) compared to
      3D conformal photon radiotherapy (3D-CRT). Late effects considered were cardiac
      mortality and secondary cancer in the lungs and breasts (for female patients).
      METHODS: Patient data were acquired for twenty-six patients (ages 12-29) who were
      treated with 3D-CRT for HL, NHL, or BC in 2010. Original CT simulation images
      were used to re-plan the patients with IMPT using commercially-available
      treatment planning software. The contours of the organs at risk were reviewed by
      a single physician and modified for consistency. The dose-volume data of the 3D
      CRT plans and the new IMPT plans were analyzed to model the risks of late
      effects. The relative seriality model was used to predict excess risk of cardiac
      mortality at fifteen years post-irradiation. A modified linear quadratic model
      was used to predict the Excess Absolute Risk (EAR) for induction of lung cancer
      and breast cancer at thirty years post-irradiation. RESULTS: For 3D-CRT and IMPT
      respectively, the mean excess risks of cardiac mortality were 0.9% and 0.5%. Mean
      EARs for lung cancer were 17.5 cases per 10,000 persons per year (PY) and 10.1
      PY. Mean EARs for breast cancer were 8.2 PY and 2.8 PY. CONCLUSIONS: IMPT may
      significantly reduce the risks of radiation-induced cardiac mortality and
      secondary cancer in the lungs and breasts of young patients receiving
      radiotherapy for HL, NHL, or breast cancer.

PMID- 28516627
TI  - Sci-Fri AM: Imaging - 07: Symmetric geometric transfer matrix partial volume
      correction technique for emission tomography: Principle, validation, and
      robustness.
AB  - Partial volume correction (PVC) is often needed to correct for limited spatial
      resolution in quantitative Positron Emission Tomography (PET) and Single Photon
      Emission Computed Tomography (SPECT) studies. In conventional region-based PVC
      methods, spill over between regions segmented from coregistered computed
      tomography (CT) or magnetic resonance (MR) images is accounted for by calculating
      regional spread functions (RSFs) in a geometric transfer matrix (GTM) framework.
      This paper describes a new analytically derived symmetric GTM (sGTM) method that
      considers spill over between RSFs rather than between regions. The sGTM is
      mathematically equivalent to Labbe's method, however it is region-based rather
      than voxel-based and it avoids handling large matrices. The sGTM method was
      validated using an MR-based 3D digital brain phantom and a physical phantom
      containing spheres 5 mm to 30 mm in diameter. The sGTM method was compared to the
      GTM method in terms of accuracy, precision, noise propagation, and robustness,
      i.e. effects of mis-registration or point spread function (PSF) estimation
      errors. The results showed that the sGTM method has accuracy similar to that of
      the GTM method, and within 5% of the true value. However, the sGTM method showed
      better precision and noise propagation than the GTM method, especially for
      spheres smaller than 13 mm. Moreover, the sGTM method was more robust than the
      GTM method when misregistration or errors in estimates of PSF occurred. In
      conclusion, the sGTM method was analytically derived and validated and shown to
      exhibit better noise characteristics and robustness compared to the GTM method.

PMID- 28516628
TI  - Sci-Sat AM: Brachy - 02: Extracting Wair from the 1976 electron beam measurements
      of domen and lamperti.
AB  - The average energy expended by an energetic electron to create an ion pair in
      air, Wair is an important quantity in radiation dosimetry. The data obtained by
      Domen and Lamperti using electron beams in the energy range from 15 to 50 MeV can
      be used to extract a value for Wair if the electron stopping powers of graphite
      and air are assumed to be known. We use Monte Carlo techniques to reanalyze these
      data and obtain a new estimate for the value of Wair Using the EGSnrc Monte Carlo
      and its associated user codes, as well as the best availabl-e stopping power data
      for graphite, we calculate the perturbation effects due to the calorimeter and
      ionization chamber and the effect of extrapolating from scattered to plane
      parallel beams. Without further adjustments, the extracted values of Wair show a
      significant trend as the mean electron energy decreases. We show that part of
      this trend can be attributed to an incorrect value of the density assigned to the
      graphite absorbers and part to the likelihood that the nominal energy assigned to
      the low-energy electron beams is not correct. Using all the data, we obtain a
      value for Wair of 33.84 eV per ion pair with a relative standard uncertainty of
      0.4 %. This result serves to complement values obtained using 60 Co gamma-rays,
      for which the value of the mean excitation of graphite contributes significantly
      to the uncertainty.

PMID- 28516629
TI  - Poster - Thur Eve - 67: Clinical results of deep inspiration breath hold
      radiation treatment for the left breast patients.
AB  - Adjuvant radiotherapy for left breast cancers increases local tumor control, but
      also increases the risk of radiation-induced cardiac disease. Deep Inspiration
      Breath Hold (DIBH) can minimize dose to the heart for left breast patients where
      the heart is within the tangential field. In this study, we evaluated the
      dosimetric benefit of DIBH technique comparing to free breathing (FB)
      radiotherapy for left breast cancer patients. Five patients with left breast
      cancer treated with DIBH technique were selected randomly. The CT scans of breath
      hold (BH) and FB were taken for every DIBH patient. Standard clinical DIBH
      intensity-modulated radiotherapy (IMRT) plans were generated with BH scan dataset
      using the Varian Eclipse TP system. The prescription dose is 4250 cGy in 16
      fractions. The BH plan was copied to the FB scan dataset and shifted accordingly
      to have the same coverage for the breast tissue, and the dose was re-calculated.
      Dose-volume histograms (DVH) of the heart and lung; mean dose and maximum dose of
      the heart were calculated and compared from the BH and FB plans for every
      patient. The lung volume is increased during BH and hence the heart is moved out
      of the field, resulting in the lower heart maximum dose. The mean dose is almost
      less than 1 Gy for all BH plans. The average mean heart dose is 0.8 Gy for BH
      plan compared to 1.6 Gy for FB plan. Patients benefit significantly from DIBH
      technique due to the very low heart dose.

PMID- 28516630
TI  - Poster - Thur Eve - 77: Coordinate transformation from DICOM to DOSXYZnrc.
AB  - DICOM format is the de facto standard for communications between therapeutic and
      diagnostic modalities. A plan generated by a treatment planning system (TPS) is
      often exported to DICOM format. BEAMnrc/DOSXYZnrc is a widely used Monte Carlo
      (MC) package for beam and dose simulations in radiotherapy. It has its own
      definition for beam orientation, which is not in compliance with the one defined
      in DICOM standard. Dose simulations using TPS generated plans require
      transformation of beam orientations to DOSXYZnrc coordinate system (c.s.) after
      extracting the necessary parameters from DICOM RP files. The transformation is
      nontrivial. There have been two studies for the coordinate transformations. The
      transformation equation sets derived have been helpful to BEAMnrc/DOSXYZnrc
      users. However, both the transformation equation sets are complex mathematically
      and not easy to program. In this study, we derive a new set of transformation
      equations, which are more compact, better understandable, and easier for
      computational implementation. The derivation of polar angle theta and azimuthal
      angle phi is similar to the existing studies by applying a series of rotations to
      a vector in DICOM patient c.s. The derivation of beam rotation Phicol for
      DOSXYZnrc, however, is different. It is obtained by a direct combination of the
      actual collimator rotation with the projection of the couch rotation to the
      collimator rotating plane. Verification of the transformation has been performed
      using clinical plans created with Eclipse. The comparison between Eclipse and MC
      results show exact geometrical agreement for field placements, together with good
      agreement in dose distributions.

PMID- 28516631
TI  - Sci-Fri PM: Delivery - 02: CT image guidance strategies for dose-adaptive IMRT of
      the prostate.
AB  - On-line CT imaging in the radiotherapy room has become the norm for targeted
      intensity-modulated radiotherapy (IMRT), enabling precise adjustments of the
      daily patient setup based on soft tissue visualization. Corrections for
      plasticity of the anatomy and dose deformation are within technological reach but
      will require more on-line resources. We have developed a computer model that
      allows exploration of "what if" scenarios for assessing the benefits of Image
      Guidance strategies in terms of the multi-fraction dose distribution and DVH
      metrics (Target D95 and rectum V70). In this work we report on changes in anatomy
      and resultant dose distribution as observed in 35 daily megavoltage CT (MVCT)
      scans of the pelvis during prostate therapy for 13 patients. Our goal is to
      assess the effectiveness and efficiency of various adaptive strategies involving
      imaging schedule with and without dose re-planning of 5-field IMRT with 18 MV x
      rays. Our research questions are: To what extent do radiation dose distributions
      delivered to individual patients (in vivo) diverge from the planned dose
      distributions (in silico)? Is there a robust schedule of CT image guidance, with
      or without dose re-planning that will mitigate discrepancies? For prostate IMRT,
      we conclude that image guidance schedule can be relaxed when generous GTV margins
      (10/7mm) are used. Tighter margins (isotropic 5 mm) reduce the dose to the rectum
      as expected. However, daily re-planning may be required to maintain adequate
      target coverage as planned when tighter margins are used.

PMID- 28516632
TI  - Poster - Thur Eve - 70: Quantification of tumour dose enhancement at kilo-voltage
      energies due to the presence of gold nanoparticles during radiation therapy:
      EGSnrcMP Monte Carlo study.
AB  - One of the greatest challenges in radiation therapy is the ability to deliver a
      lethal dose of radiation to a tumour while sparing the surrounding normal
      tissues. In theory, the dose delivered to a tumour during photon-based radiation
      therapy can be enhanced by loading high atomic number (Z) materials into the
      tumour, which results in greater photoelectric absorption and hence increased
      photoelectron fluence within the tumour than in surrounding tissues. The EGSnrcMP
      Monte Carlo code, together with DOSXYZnrc, a three-dimensional voxel dose
      calculation module has been used to study the macroscopic dose enhancement factor
      (MDEF) in a tumour infused with gold nanoparticles at the kilo-voltage energies.
      We observed that gold nanoparticles infused in a tumour irradiated with kilo
      voltage energies has the potential to enhance the tumour dose by a factor ranging
      from 0.25 to about 5 depending on the mean energy of the beam and the
      concentration of gold nanoparticles in the tumour. The increase in dose can be
      attributed to the significant increase in the photoelectron fluence within the
      tumour loaded with gold particles during the irradiation. Future studies will
      involve the characterization of the MDEF at megavoltage energies.

PMID- 28516633
TI  - Sci-Fri PM: Delivery - 05: A complete set of VMAT machine-specific QA tests using
      EPID.
AB  - During a VMAT (Volumetric Modulated Arc Therapy) radiation delivery, various
      machine parameters (gantry position and speed, MLC leaves position, dose rate,
      etc) have to be highly synchronized and coordinated. To ensure that all of the
      machine components are effectively operating together requires unique machine
      specific quality assurance (QA) tests. The purpose of this work is to describe a
      complete set of VMAT machine-specific QA tests using Electronic Portal Imaging
      Device (EPID). To address the need for VMAT machine-specific QA tests, Varian has
      recommended 6 EPID-based tests for commissioning and QA of RapidArcTM capable
      machines. Recent studies have identified that these Varian tests do not define a
      complete set of tests needed for adequate commissioning and machine-specific QA
      of RapidArc machines. The goal of this work is twofold: a) to report and discuss
      the results of the original 6 Varian's EPID-based tests, and b) to extend the
      original set by adding 2 more EPID-based tests, which results in a more complete
      and comprehensive set of tests. We have demonstrated that the Varian EPID-based
      QA tests can be used to verify that the synchronization of Dose Rate, Gantry
      Speed and MLC Leaves speed is generally to within 1.5% during a RapidArc
      delivery. Also, the gantry rotation does not have any significant effect on MLC
      leaves positional accuracy during a RapidArc delivery. Finally, we have
      introduced a new EPID-based QA test, which can be used to verify that the angular
      accuracy of the gantry position during a RapidArc delivery is to within ~1
      degree.

PMID- 28516634
TI  - Sci-Sat AM: Brachy - 04: Neutron production around a radiation therapy linac
      bunker - monte carlo simulations and physical measurements.
AB  - Photoneutrons are a major component of the equivalent dose in the maze and near
      the door of linac bunkers. Physical measurements and Monte Carlo (MC)
      calculations of neutron dose are key for validating bunker design with respect to
      health regulations. We attempted to use bubble detectors and a 3 He neutron
      spectrometer to measure neutron equivalent dose and neutron spectra in the maze
      and near the door of one of our bunkers. We also ran MC simulations with MCNP5 to
      measure the neutron fluence in the same region. Using a point source of neutrons,
      a Clinac 1800 linac operating at 10 MV was simulated and the fluence measured at
      various locations of interest. We describe the challenges faced when measuring
      dose with bubble detectors in the maze and the complexity of photoneutron
      spectrometry with linacs operating in pulsed mode. Finally, we report on the
      development of a userfriendly GUI for shielding calculations based on the NCRP
      151 formalism.

PMID- 28516635
TI  - Sci-Fri PM: Delivery - 09: Response of a tumor xenograft model to radiation
      therapy using magnetic resonance spectroscopy.
AB  - 9.4T 1 H magnetic resonance spectroscopy (MRS) was utilized to track the response
      of mouse xenograft glioblastoma multiform (GBM) brain tumors to single fraction
      radiation therapy. Six metabolites were analyzed with LCModel: alanine (Ala), myo
      inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine
      and glutamate (Glu + Gln), and total choline (glycerophosphocholine +
      phosphocholine) (GPC + PCh). 11 mice received 800 cGy of 200 kVp x-rays, 5 were
      untreated controls. PRESS spectra (27 MUL volumes) were acquired at multiple time
      points for treated and control animals. In treated animals, all metabolite :
      water ratios decreased 3 days post-treatment, with further decreases at day 7,
      and then increases at day 14 relative to the 7 day mark. Concentrations on day 7
      relative to pre-treatment were as follows: 0.42 (Ala), 0.43 (Ins), 0.68 (Tau),
      0.52 (GPC+PCh), 0.49 (Cr + PCr) and 0.78 (Glu + Gln). Metabolite ratios did not
      correlate with tumor volume in control animals, suggesting a real therapeutic
      response was observed. Our 1 H MRS data suggests that perturbations in the
      metabolic signature of GBM cancers occur in response to irradiation. Such changes
      in the metabolite : water concentration ratios could potentially be exploited for
      the improvement of radiotherapy.

PMID- 28516636
TI  - Sci-Sat AM: Brachy - 08: MRI-guided planning and maximum achievable HR-CTV doses
      in cervix brachytherapy.
AB  - PURPOSE: To present an institutional experience with MRI-based intracavitary
      brachytherapy planning for cervix cancer treatments using the EMBRACE protocol
      and to evaluate maximum HR-CTV doses that can be achieved when OAR (bladder,
      rectum, and sigmoid) doses are allowed to equal GECESTRO recommended thresholds.
      METHOD: Dose metrics from treatment plans for 20 patients created using MR images
      (for contouring HR-CTV and OARs) fused with CT images (for applicator
      reconstruction) are presented. Starting with a standard Manchester loading, plans
      were manually optimized (MO) by adjusting dwell positions and times to obtain the
      desired HR-CTV D90 target coverage of 35 Gy while limiting OAR doses to below
      recommended tolerances. In addition, retrospective planning was done using: (i)
      volume optimization (VO) to compare differences with MO in obtaining the desired
      target coverage; and (ii) MO and VO techniques to get the highest possible HR-CTV
      coverage by allowing OAR doses to equal tolerance values. The latter plans are
      referred to as MAX plans. RESULTS AND CONCLUSIONS: 3D MRI-guided treatment
      planning for cervix brachytherapy was shown to improve dose-volume coverage of
      the target and OARs. MO could conform HR-CTV D90 to the prescribed dose similar
      to the VO technique. Sigmoid was often the dose limiting structure. With respect
      to the prescribed HR-CTV D90 dose of 35 Gy, MAX plans could increase the
      prescribed dose by about 22% and 30% for MO and VO plans, respectively, without
      exceeding OAR thresholds. Consequently, dose escalation for MRI-guided cervix
      brachytherapy appears feasible should clinical circumstances warrant.

PMID- 28516637
TI  - Poster - Thur Eve - 72: Conversion of helical tomotherapy plans into clinically
      favourable step-and-shoot IMRT plans deliverable on a c-arm linac.
AB  - The treatment planning software SharePlan is designed to convert dose
      distributions generated by the TomoTherapy planning station into step-and-shoot
      IMRT plans deliverable on a c-arm linear accelerator. Five anal canal patients
      who were planned for TomoTherapy treatments were exported into a SharePlan system
      and plans were generated for delivery on an Elekta Synergy unit. A total of 80
      plans were generated for those five patients, with either seven, nine, eleven or
      twenty-one gantry angles and different priorities between focusing on matching
      either the target doses or healthy tissue sparing of the TomoTherapy plan. The
      plans generated by SharePlan, while often not matching target coverage at
      prescription, matched well the TomoTherapy coverage at 95% and 105% of the
      prescription dose. Organ at risk dose, when heavily emphazied in the SharePlan
      calculations matched or bettered the TomoTherapy dose due to the placement of the
      beams and the sharper sup-inf fall off of the dose distribution on a linac. For
      one of the patients, it was possible to produce a better DVH with SharePlan than
      the original TomoTherapy plan for those reasons. The TomoTherapy plans boasted
      significantly shorter delivery times than the plans generated with SharePlan.

PMID- 28516638
TI  - Sci-Fri AM: Imaging - 06: The role of body mass and gender in atlas construction
      for attenuation correction in PET/MRI.
AB  - Attenuation correction (AC) in PET/MRI is difficult as there is no clear
      relationship between MR signal and 511 keV attenuation coefficients (MU) as there
      is with CT. One approach is to register a pre-defined atlas of MU to the PET/MRI
      for AC. However, the design of the atlas may strongly influence the quantitative
      accuracy of the AC. Here we compare 3 different atlas design approaches and
      evaluate their performance in an oncology patient population. The 3 strategies
      were: use of BMI-dependent atlases; use of gender-dependent atlases, and use of a
      gender- and sex-independent atlas. Seventeen patients were imaged with FDG PET/CT
      and subsequently scanned with 3T MRI. MR and PET/CT images were coregistered, CT
      scans converted to MU-maps, and the resulting MRI/MU-map paired data were used to
      construct 6 atlases: averaged male and female atlases, averaged BMI-specific
      atlases (obese >30, overweight 25-29.9, Normal 18.5-24.9), and a single atlas
      comprised of all patients averaged together. The atlases were then used for PET
      AC for patients not included in the construction of the atlas in a leave-one-out
      manner. Resulting PET images were compared to each other and to the gold-standard
      CT-based PET reconstructions across all voxels and tissue-specific regions (soft
      tissue, bone, lung). Sex-specific atlases yielded best results (average relative
      percent error over the 3 VOIs = 0.4509) & BMI-based atlases yielded highest
      average relative percent error at 0.9340. In all cases, highest errors were in
      the VOIs located in the livers.

PMID- 28516639
TI  - Sci-Sat AM: Brachy - 01: Evaluation of dose-volume metrics for microbeam
      radiation therapy.
AB  - Microbeam radiation therapy (MRT) is an experimental technique delivering an
      array of high dose synchrotron X-ray microbeams. Development of metrics to
      predict the biological efficacy of MRT dose distributions is needed to guide
      further MRT research and for potential translation to human trials. The most
      commonly used metric is the peak-to-valley-dose ratio (PVDR) relating the dose at
      the microbeam center to that between two microbeams. We investigate three
      additional metrics that characterize dose distributions from a more volumetric
      perspective - the peak-to-mean-valley-dose ratio (PMVDR), mean dose, and
      percentage volume below a threshold. The metrics are evaluated for Monte Carlo
      simulations of dose distributions in three cubic head phantoms (2, 4 and 8 cm
      side lengths) for microbeam widths of 25, 50, and 75 MUm and centre-to-centre
      spacings of 100, 200 and 400 MUm. The ratio of the PMVDR to the PVDR varied from
      0.24 to 0.80 for the different configurations, indicating a difference in the
      predicted geometric dependence of outcome for these two metrics. The mean dose
      was 102, 79, and 42 % of the mean skin dose for the 2, 8, and 16 cm head
      phantoms, respectively. The percentage volume below a 10% dose threshold was
      highly dependent on geometry, with ranges for the different collimation
      configurations of 2 - 87% and 33 - 96% for the 2 and 16 cm heads, respectively.
      Different dose-volume metrics exhibit different dependencies on MRT geometry
      parameters, suggesting that reliance on PVDR as a predictor of therapeutic
      outcome may be insufficient.

PMID- 28516640
TI  - Poster - Thur Eve - 66: A planning comparison between RapidArc and intensity
      modulated radiotherapy for head and neck cancer.
AB  - Volumetric modulated arc therapy (VMAT) has recently been used to improve the
      dose distribution and efficiency of treatment delivery over the standard
      intensity-modulated radiotherapy (IMRT) technique. This study compares the
      dosimetry between RapidArc plan and standard IMRT plan for head and neck cancer.
      Three head and neck patients treated clinically with sliding window intensity
      modulated radiotherapy (IMRT) technique at Grand River Regional Cancer Center
      were selected randomly and re-planned using RapidArc technique with 6 MV photon
      beams generated by a Varian 21EX linac with 120-leaf multileaf collimator. Three
      dose prescriptions were used to deliver 70 Gy, 63 Gy and 58.1 Gy to the regions
      of the primary tumors, intermediate-risk nodes and low-risk nodal level,
      respectively, in 35 fractions. Dosimetric comparison based on the dose-volume
      histogram, target coverage, organ at risk (OAR) dose sparing were studied between
      the RapidArc plan and IMRT plan. RapidArc technique from Varian Medical Systems
      showed superior target coverage, better OAR sparing, fewer monitor units per
      fraction with less treatment time over IMRT technique for head and neck cancers.
      The average homogeneity index, defined as the difference between the percentage
      dose covering 5% and 95% of the PTV, is 9.5 for RapidArc plan and 10.5 for IMRT
      plan. All RapidArc plans met the dose objectives for the primary OAR: spinal
      cord, brainstem, brain etc. Both parotid mean dose and D50% are lower for
      RapidArc plan than those of the IMRT plan. The technique is currently being used
      clinically at our cancer center.

PMID- 28516641
TI  - Sci-Sat AM: Brachy - 12: Resolving the olefinic lipid resonance from water in
      proton magnetic resonance spectra of vertebral bone marrow at 3 T.
AB  - Proton magnetic resonance spectroscopy (MRS) of vertebral lipids has been shown
      to be relevant in the study of cancer. The olefinic resonance (~ 5.4 ppm) yields
      a measure of lipid unsaturation. However, its measurement with standard short
      echo time (TE) MRS sequences is difficult due to the large overlapping water
      signal. The purpose of this work is to optimize the TE of a PRESS (Point RESolved
      Spectroscopy) sequence to measure the olefinic resonance from spinal bone marrow
      with minimal losses due to J-coupling and minimal contamination from water at 3
      T, a field strength becoming more common in the clinic. Experiments were
      conducted on nine oils and on L4 vertebral bone marrow in vivo at 3 T. The
      methylene (or methyl + methylene), and olefinic resonances were measured with
      PRESS using multiple TEs. The effects of J-coupling evolution of the olefinic
      protons appeared to be minimal when TE = 200 ms. The TE = 200 ms
      olefinic/methylene peak area ratios calculated for each oil correlated well with
      ratios deduced from oil compositions in the literature (R2 = 0.92). The TE = 200
      ms PRESS spectra obtained from vertebra of four volunteers showed negligible
      contribution from water to the olefinic resonance, thereby enabling the olefinic
      peak area to be quantified more accurately. The results of this work demonstrate
      that a PRESS sequence with TE = 200 ms is suitable for measuring relative levels
      of lipid unsaturation and for resolving the olefinic resonance from contaminating
      water signal in spinal bone marrow.

PMID- 28516642
TI  - Poster - Thur Eve - 76: A quality control to achieve planning consistency in arc
      radiotherapy of the prostate.
AB  - PURPOSE: To report a quality control program in prostate radiation therapy at our
      center that includes semi-automated planning process to generate high quality
      plans and in-house software to track plan quality in the subsequent clinical
      application. MATERIAL AND METHODS: Arc planning in Eclipse v10.0 was preformed
      for both intact prostate and post-prostatectomy treatments. The planning focuses
      on DVH requirements and dose distributions being able to tolerate daily setup
      variations. A modified structure set is used to standardize the optimization,
      including short rectum and bladder in the fields to effectively tighten dose to
      target and a rectum expansion with 1cm cropped from PTV to block dose and shape
      posterior isodose lines. Structure, plan and optimization templates are used to
      streamline plan generation. DVH files are exported from Eclipse to a quality
      tracking software with GUI written in Matlab that can report the dose-volume data
      either for an individual patient or over a patient population. RESULTS: For 100
      intact prostate patients treated with 78Gy, rectal D50, D25, D15 and D5 are
      30.1+/-6.2Gy, 50.6+/-7.9Gy, 65.9+/-6.0Gy and 76.6+/-1.4Gy respectively, well
      below the limits 50Gy, 65Gy, 75Gy and 78Gy respectively. For prostate bed with
      prescription of 66Gy, rectal D50 is 35.9+/-6.9Gy. In both sites, PTV is covered
      by 95% prescription and the hotspots are less than 5%. CONCLUSION: The semi
      automated planning method can efficiently create high quality plans while the
      tracking software can monitor the feedback from clinical application. It is a
      comprehensive and robust quality control program in radiation therapy.

PMID- 28516643
TI  - Sci-Fri PM: Delivery - 01: Approach to evaluate the accuracy of individual
      control-points of a VMAT delivery measured by an EPID.
AB  - A unique approach that uses Monte Carlo (MC) methods to validate time-resolved
      measured dose by an electronic portal imaging device (EPID) during delivery of
      volumetric modulated arc therapy (VMAT) treatments was investigated. Time
      resolved dose is simultaneously scored in both the patient and EPID geometries. A
      RapidArc(c) verification plan was generated and delivered on a homogeneous
      cylindrical phantom. Portal images were collected using an aS1000 amorphous
      silicon EPID attached to a Varian Clinac 2100ix. The images were acquired in the
      continuous acquisition mode and in-house analysis software was used to obtain
      images for each control point. We performed MC simulation and dose calculation of
      the verification plan using the EGSnrc MC package. The MC phantom file contains
      both the EPID model and the cylindrical phantom derived from the CT data sets.
      For the individual control point simulation, we rotate the phantom only using the
      gantry angle information. For this work, we calculated dose distributions for
      five control points (out of a total of 177) in the verification plan. The
      normalized measured and calculated data were compared using the chi comparison
      (computationally efficient implementation of gamma). The chi comparison between
      measured and calculated doses for the five control points using criteria of 3%
      and 3mm revealed an average of 88.7% of all pixels having chi<1. The agreement
      will improve when the measured portal images are corrected for flood field and
      support-arm backscatter effects. This approach allows us to obtain both the EPID
      dose and the phantom/patient dose. These preliminary results demonstrate
      promising accuracy. With further improvements, this approach will be useful for
      benchmarking of time-resolved EPID dose applications intended for rotational IMRT
      QA and adaptive radiation therapy.

PMID- 28516644
TI  - Poster - Thur Eve - 69: Electron beam dosimetry in heterogeneous phantoms using
      the MAGIC normoxic polymer gel.
AB  - Recently, radiation sensitive polymer gels are being used as a reliable dosimetry
      method for three-dimensional (3D) verification of radiation doses in clinical
      use. Some properties of gel dosimeters have made them useful in verifying complex
      situations in electron therapy. The aim of this study was to experimentally
      evaluate the influence of tissue inhomogeneities on electron beam dose
      distributions by use of polymer gel dosimetry. Another purpose was to evaluate
      the appropriateness of polymer gels for electron beam dosimetry applications. A
      cylindrical phantom filled with MAGIC polymer gel with a polyacrilic wall (rho =
      1.18 g.cm-3 ) was placed in a Perspex water-filled tank exactly underneath the
      bone inhomogeneity region .Then, the slab phantom was irradiated with a dose of
      5Gy of 8MeV electrons to measure the dose distribution beyond the heterogeneity
      region. Afterwards, another cylindrical gel phantom similar to the above was used
      and irradiated with the same dose of 15 MeV electrons to measure the dose
      distribution beyond the same heterogeneity region. The same mentioned setup was
      repeated for measurement of the dose distribution beneath the air heterogeneity
      and homogenous phantom. The results of gel dosimetry under bone inhomogeneity
      have shown a reduction in dose. This is related to the high mass stopping and
      mass scattering powers of bone tissue. In addition, dose enhancement is seen
      laterally near the bone-tissue interface, due to increased side scattering of
      electrons. Hot and cold scatter lobes under heterogeneity regions are other
      effects that can be seen. The results of gel dosimetry under the air
      inhomogeneity have shown an increase in dose. This is related to the low mass
      stopping and mass scattering powers of the air cavity. When a high energy beam
      passes through a low-density medium or an air cavity, electronic equilibrium is
      lost along the central axis of the beam .The dose rebuild up is a consequence of
      this electronic disequilibrium. An overall good agreement was found between
      measurements with gel and with a diode detector for the single beam experiment.
      Electron dose distributions are significantly altered in the presence of tissue
      inhomogeneities such as bone and air cavities which are related to mass stopping
      and mass scattering powers of heterogeneous materials.

PMID- 28516645
TI  - Sci-Fri AM: Imaging - 03: Temperature dependence of a SiPM detector for an MR
      compatible PET system.
AB  - Silicon photomultiplier (SiPM) detectors are rapidly becoming the detector of
      choice for research and development of new detectors for positron emission
      tomography (PET) due to their combination of high gain, fast timing, compact form
      factor and ability to function in a magnetic field. We are investigating using
      SiPM based detectors in a compact PET system designed to be inserted into a 7T
      animal MRI system and enable simultaneous PET/MRI imaging. In order to understand
      the level of thermal stability required for this PET system, we examined the
      stability of a prototype SiPM detector vs. temperature. A detector was
      constructed using a SensL SPMArray4 SiPM array coupled to a LYSO scintillator
      crystal array. The temperature of the detector was varied between 23 and 60
      degrees C in 5 degrees C steps. At each temperature setting data were collected
      to characterize the detector flood histogram, photopeak amplitude and energy
      resolution at 511 keV, timing resolution and signal arrival time. While the flood
      image showed no noticeable changes with temperature, the 511 keV photopeak
      amplitude showed a linear decrease of 1.5%/ degrees C and the energy resolution
      degraded by 0.08%/ degrees C. The timing resolution degraded by 1.5 ns, from 3.5
      ns to 5 ns when the temperature changed from 23 to 60 degrees C. Over this
      temperature range there was a shift in the signal arrival time of approximately 3
      ns. These results demonstrate that the detector can be operated over a wide range
      of temperature, giving a large degree of flexibility in choosing an operating
      temperature set-point for our PET system.

PMID- 28516646
TI  - Sci-Sat AM: Brachy - 03: Feasibility study of the determination of absorbed dose
      to water using a fricke based system.
AB  - By measuring the dose to water directly a metrology standard, independent of air
      kerma, can be developed to make the basis of HDR brachytherapy dosimetry
      consistent with current dosimetry methods for external radiation beams. The
      Fricke dosimeter system, a liquid chemical dosimeter, provides a means of
      measuring the absorbed dose rate to water directly by measuring the radiation
      induced change in absorption of the Fricke solution. In an attempt to measure the
      absorbed dose to water directly for a 192 Ir HDR brachytherapy source a ring
      shaped Fricke holder was constructed from PMMA, essentially following the work of
      Austerlitz et al. (Med. Phys. 2008). Benchmark measurements conducted in a 60 Co
      beam yielded a standard uncertainty in the absorption reading of 0.16 %,
      comparable with previous results in the literature. Measurements of the standard
      uncertainty of the control (unirradiated) solution using the holder yielded 0.2
      %, indicating good process control and minimal contamination from the holder
      itself. However, it was found that the holder sealing method (to allow
      measurements in a water phantom) significantly contaminated the Fricke solution,
      resulting in an excessive background reading. Irradiations were therefore
      conducted in air to determine the feasibility of the procedure. Irradiations with
      a 17 GBq source gave a standard uncertainty of approximately 0.5 %, indicating
      that the target uncertainty of 1.5% for the measurement of absorbed dose to water
      using a Fricke-based primary standard is achievable. This would be comparable
      with calorimeter-based systems currently being developed.

PMID- 28516647
TI  - Sci-Fri PM: Delivery - 08: Characterizing the spatially varying fluence and
      spectra of a kV imaging source for dose calculations.
AB  - Kilovoltage (kV) daily image-guided radiotherapy (IGRT) procedures accumulate
      radiation dose within the patient that is currently not routinely incorporated in
      the treatment plan. As part of the process of developing a patient-specific kV
      dose computation tool, the kV x-ray source must be characterized. We propose a
      simple, clinically feasible experimental characterization method using in-air
      dose measurements along the transverse axis. We determine half-value layer (HVL)
      along the transverse axis, from which we derive the HVL-specific mass-absorption
      coefficient, which is used to determine beam fluence. These values are
      interpolated over the entire field. The spectrum at each interpolation point in
      the field is found from HVL and accelerating potential (kVp) using third-party
      software Spektr. We use this method to characterize the spatially varying fluence
      and spectra of a Varian(r) On-Board Imaging(r) source for energies 80, 100 and
      125 kVp. This characterization is used to compute dose within a heterogeneous
      phantom, using our previously validated in-house dose computation software, which
      we compare with relative dose measurements. We show that for a 10*10 cm2 field
      size using no added filtration, the agreement for all three energies is within 2%
      for the central depth-dose profile and within 2.6% for the transverse profiles.
      This clinically feasible experimental characterization method for kV imaging
      sources represents a crucial step in the development of a patient-specific dose
      computation tool.

PMID- 28516648
TI  - Sci-Sat AM: Brachy - 07: Plastic scintillation detector validation for kV
      dosimetry.
AB  - PURPOSE: To characterize the plastic scintillation detectors (PSDs) response in
      the diagnostic energy range. A fast and adaptable method for real-time dosimetry
      in superficial x-ray therapy and interventional radiology is proposed. METHOD: A
      PSD (1 mm diameter and 10 mm long) is coupled to a 5 m long optical fiber.
      Scintillation photons are guided to a polychromatic photodiode which provides an
      electrical current proportional to the input light signal. If the incident energy
      spectrum is known, the dose measured in the PSD's polystyrene sensitive volume
      can be converted to score dose in any other media such as air, water or soft
      tissues using the large cavity theory (LCT). A software simulating x-ray tube
      spectra and filtration has been benchmarked and is used for analysis. The method
      is confirmed by Monte Carlo simulations. RESULTS: PSDs cannot be assumed energy
      independent with low-energy photons as a factor 2 has been observed in the energy
      response between 80 kVp and 150 kVp. When the dose is converted to the desired
      medium, the PSD's energy dependence is compensated and a 2.1% standard deviation
      was observed upon the studied energy ranges, which is inside the measurement and
      calculation uncertainties. Percent depth dose (PDD) measurements are in good
      agreement with Monte Carlo simulations and results can be improved if the
      proposed method is applied to compensate beam hardening. CONCLUSION: PSDs present
      great potential for real-time dose measurements with radiologic photon energy.

PMID- 28516649
TI  - Poster - Thur Eve - 71: Improved dose accuracy for plan checking IMRT breast
      plans.
AB  - Dose verification as part of plan checking is a critical component of high
      quality patient care. IMSure QA is a software platform used at the BC Cancer
      Agency that facilitates dose verification for both conformal and IMRT plans. We
      have recently initiated treating breast tangents using IMRT at the Fraser Valley
      Centre and noted increased dose discrepancies (mean difference of -3%) between
      Eclipse and IMSure's QA module. We identified two potential sources of error: air
      flash and tissue heterogeneity. We extend our generated fluences 3cm past the
      breast contour and into air to account for breathing, set-up uncertainties and
      swelling. IMSure does not account for the fluence in air or air flash. We present
      an air-flash-correction factor based on the ratios of TMRs and Phantom Scatter
      Factors which use the field sizes of fields with and without the air flash. In
      addition, we present a method to improve the heterogeneity correction used by
      IMSure to better match that used by AAA. Effectively we remove the IMSure's
      inherent heterogeneity correction and manually apply a AAA-based heterogeneity
      correction factor. We evaluated our correction factors on a sample of 8 patients
      (32 fields) using ANOVA methods to determine which dose corrections most
      accurately reproduce Eclipse's values. We found the air-flash correction coupled
      with IMSure's inherent-heterogeneity correction has the best dose accuracy (mean
      difference improved from -3% to 0.3%). The AAA-heterogeneity correction alone
      also improved the accuracy (mean difference improved from -3% to - 1.5%), which
      is acceptable for plan checking purposes.

PMID- 28516650
TI  - Sci-Fri AM: Imaging - 05: Cone-beam computed tomography for breast biopsy
      analysis: Simulations.
AB  - PURPOSE: To determine the feasibility and potential utility of cone beam CT on
      breast biopsies. METHODS: CBCT simulations were done with a setup which emulates
      an MX-20 digital specimen radiography system (Faxitron X-Ray Corporation,
      Chicago, IL), albeit a DQE = 1 was assumed. The phantom consisted of a 5mm
      diameter cylinder with a length of 5mm, made up of a homogeneous 50:50 mixture of
      fibrous and fatty tissue. Small cancerous spheres (lesions) with diameters
      ranging from 5 to 500 MUm were embedded. Projections were acquired at
      magnification 5 using 26 kV-0.3 mA-3.8 sec beams. Images were reconstructed using
      a varied number of projections (50, 100, 150, 300). Values of contrast and SNR
      were calculated between the lesions and nearby regions. Noise was estimated by
      generating 10 images for each task. Scatter was found to be negligible. RESULTS:
      The 50 MUm spheres were only visible when at least 150 projections were used, but
      the 100 MUm ones were visible regardless of the number. SNR increased with the
      number of projections, whereas contrast was insensitive. For >=100 MUm spheres
      contrast ranged from 0.26 on the outer radial edge to 0.28 nearer the center. The
      SNRs for 100 MUm spheres were above 5 for reconstructions composed of >=100
      projections. Cancerous lesions within a fibrous biopsy may be detectable.
      CONCLUSIONS: The findings from this simulation study suggest that CBCT for breast
      biopsy characterization via the MX-20 system could be of potential use to see
      structures on the order of 100 MUm.

PMID- 28516651
TI  - Sci-Fri PM: Delivery - 12: Scatter-B-Gon: Implementing a fast Monte Carlo cone
      beam computed tomography scatter correction on real data.
AB  - A fast and accurate MC-based scatter correction algorithm was implemented on real
      cone-beam computed tomography (CBCT) data. An ACR CT accreditation phantom was
      imaged on a Varian OBI CBCT scanner using the standard-dose head protocol (100
      kVp, 151 mAs, partial-angle). A fast Monte Carlo simulation developed in the
      EGSnrc framework was used to transport photons through the uncorrected CBCT scan.
      From the simulation output, the contribution from both primary and scattered
      photons for each projection image was estimated. Using these estimates, a
      subtractive scatter correction was performed on the CBCT projection data.
      Implementation of the scatter correction algorithm on real CBCT data was shown to
      help mitigate scatter-induced artifacts, such as cupping and streaking. The
      scatter corrected images were also shown to have improved accuracy in
      reconstructed attenuation coefficient values. In three regions of interest
      centered on material inserts in the ACR phantom, the reconstructed CT numbers
      agreed with clinical CT scan data to within 35 Hounsfield units after scatter
      correction. These results suggest that the proposed scatter correction algorithm
      is successful in improving image quality in real CBCT images. The accuracy of the
      attenuation coefficients extracted from the corrected CBCT scan renders the data
      suitable for adaptive on the fly dose calculations on individual fractions, as
      well as vastly improved image registration.

PMID- 28516652
TI  - Sci-Sat AM: Brachy - 11: Improving treatment planning for I-125 lung
      brachytherapy using Monte Carlo methods.
AB  - 125 I brachytherapy used in conjunction with sublobar resection to treat stage I
      non-small cell lung cancer has been reported to improve disease-free and overall
      survival rates compared with resection alone. Treatments are planned intra
      operatively using seed spacing nomograms or tables to achieve a prescription dose
      defined 5 mm above the implant plane. Dose distributions for patients treated
      with this technique at the Mayo Clinic Rochester were reanalyzed using a Monte
      Carlo (MC) calculation; significant differences were observed between the
      standard TG-43 dose calculations and the actual dose delivered as determined by
      MC. This work investigates differences between TG-43 calculated prescription
      doses and those calculated in more accurate models. Monte Carlo calculations are
      performed using the EGSnrc user-code BrachyDose with a number of lung tissue
      phantom models including patient CT-derived phantoms. Seed spacing nomograms
      using these models are recalculated by determining the dose to the prescription
      point using the activities per seed required to produce a prescription dose of
      100 Gy with the TG-43 point source formalism. Models using nominal density lung
      or CT-derived density lung tissue result in a significant increase in dose to the
      prescription point (up to approximately 25%) compared to TG-43 calculated doses.
      The differences observed suggest that patients routinely receive significantly
      higher doses than planned using TG-43 derived nomograms. Additionally, deviation
      from TG-43 increases as seed spacing increases. Media heterogeneities
      significantly affect dose distributions and prescription doses for 125 I lung
      brachytherapy, underlining the importance of using model-based dose calculation
      algorithms to plan and analyze these treatments.

PMID- 28516653
TI  - Poster - Thur Eve - 75: Towards MR only simulation: MR based digitally
      reconstructed radiograph of head and neck.
AB  - PURPOSE: To develop a practical method to obtain bony structures from Magnetic
      Resonance (MR) images and to create MR- based digitally reconstructed radiographs
      (DRR) for MR only simulation. METHODS AND MATERIALS: Using T1-weighted MR images,
      air regions including the sinuses and the airway in the head and neck were
      manually contoured. The bone and soft tissue masks were automatically generated
      based on the statistical data calculated from the air contour and MR intensities.
      "CT like" MR images were generated by mapping the MR intensities of the voxels
      within these masks into the CT number ranges of these tissues. The MR-based DRRs
      created from "CT like" MR images were quantitatively evaluated using the co
      registered MR and CT images of 10 stereotactic radiosurgery CNS patients. Ten
      anatomical control points, set on the contours of the skull segmented using a
      threshold of 300 HU were used to determine the differences in distance between MR
      based DRRs and CT-based DRRs, and to evaluate the geometrical accuracy of MR
      based DRRs. RESULTS: The bony structures were visible in the MR-based DRRs. The
      mean geometric difference and standard deviation between the ten anatomical
      control points on MR- based and CT-based DRRs were -0.03+/-1.11 mm (including
      uncertainty of image fusion). The maximum distance difference was 1.67mm.
      CONCLUSIONS: The study provides a practical method to generate MR- based DRRs
      from MR-only simulations of the head and neck regions. The image quality and
      anatomical accuracy of MR-based DRRs is comparable to that of CT-based DRRs.

PMID- 28516655
TI  - Poster - Thur Eve - 68: Evaluation and analytical comparison of different 2D and
      3D treatment planning systems using dosimetry in anthropomorphic phantom.
AB  - PURPOSE: The aim of this study was to evaluate and analytically compare different
      calculation algorithms applied in our country radiotherapy centers base on the
      methodology developed by IAEA for treatment planning systems (TPS) commissioning
      (IAEA TEC-DOC 1583). MATERIAL & METHODS: Thorax anthropomorphic phantom (002LFC
      CIRS inc.), was used to measure 7 tests that simulate the whole chain of external
      beam TPS. The dose were measured with ion chambers and the deviation between
      measured and TPS calculated dose was reported. This methodology, which employs
      the same phantom and the same setup test cases, was tested in 4 different
      hospitals which were using 5 different algorithms/ inhomogeneity correction
      methods implemented in different TPS. The algorithms in this study were divided
      into two groups including correction based and model based algorithms. RESULTS: A
      total of 84 clinical test case datasets for different energies and calculation
      algorithms were produced, which amounts of differences in inhomogeneity points
      with low density (lung) and high density (bone) was decreased meaningfully with
      advanced algorithms. The number of deviations outside agreement criteria was
      increased with the beam energy and decreased with advancement of the TPS
      calculation algorithm. CONCLUSION: Large deviations were seen in some correction
      based algorithms, so sophisticated algorithms, would be preferred in clinical
      practices, especially for calculation in inhomogeneous media. Use of model based
      algorithms with lateral transport calculation, is recommended. Some systematic
      errors which were revealed during this study, is showing necessity of performing
      periodic audits on TPS in radiotherapy centers.

PMID- 28516654
TI  - Sci-Fri AM: Imaging - 09: Serial estimation of cross-talk for correction in dual
      isotope imaging with dynamic tracers.
AB  - The recent radioisotope shortage has led to interest in non-Tc99m-based tracers.
      We have developed a novel I-123-labelled myocardial perfusion imaging tracer. We
      compare the I123-tracer to the clinical standard of Tc99m tetrofosmin in vivo in
      a rat model using a small-animal SPECT/CT camera. SPECT distinguishes different
      isotopes based on the different energies of the emitted gamma rays and thus
      allows simultaneous comparison of two tracer distributions in the same animal.
      Dual-isotope imaging is complicated by cross-talk between the energy windows of
      the isotopes. Standard energy-window-based correction methods are difficult to
      employ because of the proximity in energy of Tc99m (140keV) and I123 (159keV).
      Imaging the second tracer's energy window prior to its injection provides an
      estimate of the cross-talk. However, this estimate is only accurate if the tracer
      distribution is static. We use serial imaging prior to the introduction of the
      second tracer to estimate the dynamics of the first tracer and interpolate the
      cross-talk images to provide a more accurate correction. We used rat models of
      myocardial disease (n=3). I123 tracer was injected and imaged for one hour at
      20min intervals. The Tc99m tetrofosmin was then injected and 30min later, a dual
      isotope image was obtained. The impact of this approach is assessed by comparing
      the differences in the Tc99m-tetrofosmin image using this method with correction
      by simple correction for physical decay. The interpolative approach improves the
      accuracy of the correction by 2%-5% and thereby enhances the comparison of the
      two tracers.

PMID- 28516656
TI  - Sci-Fri AM: Imaging - 02: High resolution detectors for PET mammography.
AB  - PURPOSE: With high specificity for malignant breast lesions, dedicated-breast
      molecular imaging systems such as positron emission mammography (PEM) have
      potential to improve the sensitivity of cancer in women with radio-dense breasts
      and to reduce the false-positive rate of breast screening when used as a
      diagnostic adjunct. For high signal-to-noise ratio and to minimize the patient
      dose, scintillation detectors in a PEM system must have high annihilation photon
      detection efficiency. This efficiency can be increased by accepting annihilation
      photons from wider incident angles and by using depth-of-interaction (DOI)
      measurement within a scintillation crystal to minimize parallax blurring. We have
      developed a dual-ended readout block (DERB) detector that uses asymmetry of
      signals from photodetectors on either end of a scintillation array to measure DOI
      and uses Anger Logic with light sharing to identify interacting crystal elements
      while minimizing the number of photodetectors required. METHODS: A prototype DERB
      detector was constructed from two arrays of silicon photomultipliers (SiPM), two
      glass optical diffusers, and an array of LYSO scintillation crystals. Assembled,
      each of the 2 * 2 SiPM arrays detect photons that are dispersed via the optical
      light diffusers originating from either end of 3 * 3 scintillation crystal
      elements. We evaluated the ability of the detector to identify the crystal index,
      resolve DOI, and discriminate energy. RESULTS: The DERB detector was able to
      clearly identify interacting crystal elements, to measure DOI with 5mm resolution
      in 2mm * 2mm * 20mm crystals, and to achieve an average energy resolution of 20%.
      CONCLUSIONS: The DERB detector characteristics suggest that it can be used to
      reduce the parallax effect in PEM systems without increasing the number of
      required photodetectors. Further investigation is warranted to improve
      performance with high optical photon detection efficiency photodetectors.

PMID- 28516657
TI  - Sci-Fri PM: Delivery - 04: Quantitative air communication testing of ion chambers
      for megavoltage dosimetry.
AB  - The valid application of the standard correction for air density (PTP in the TG
      51 protocol) requires that for a vented ion chamber (basically all reference
      class ion chambers) the air cavity does indeed communicate directly with the
      external environment. However, this assumption is not tested by users, and not
      universally verified by calibration laboratories. A system has therefore been
      developed at the National Research Council to test air communication of
      cylindrical and parallel-plate ion chambers. The systems is based on measurements
      in a vacuum vessel with a Sr-90 check source; the procedure is simple and quick
      and can measure ionization currents over the pressure range 0 kPa (atmospheric)
      to -20kPa (0.8 atm) with an uncertainty better than 0.2%. Investigation of a wide
      range of chamber types shows that for a coarse check on chamber performance
      (i.e., that the chamber is vented to atmosphere) measurement at a single polarity
      is sufficient (total test time less than 15 minutes) but for accurate
      characterization of the chamber performance, data at both polarities must be
      acquired. The accuracy of the system means that it can potentially be used to
      investigate: i) the validity of the pressure correction, and ii) the source of
      the polarity correction in cylindrical and parallel-plate chambers. The air
      communication test will be implemented as part of the standard calibration
      services provided by NRC for external beam radiotherapy.

PMID- 28516658
TI  - Sci-Fri PM: Delivery - 07: Cyberknife relative output factor measurements using
      fiber-coupled luminescence, MOSFETS and RADPOS dosimetry system.
AB  - Novel dosimetry systems based on Al2 O3 :C radioluminescence (RL) and a 4D
      dosimetry system (RADPOS) from Best Medical Canada were used to measure the
      relative output factor (ROF) on Cyberknife. Measurements were performed in a
      solid water phantom at the depth of 1.5 cm and SSD = 78.5 cm for cones from 5 to
      60 mm. ROFs were also measured using a mobileMOSFET system (Best Medical Canada)
      and EBT1 and EBT2 GAFCHROMIC(r) (ISP, Ashland) radiochromic films. For cone sizes
      12.5-60 mm all detector results were in agreement within the measurement
      uncertainty. The microMOSFET/RADPOS measurements (published corrections applied)
      yielded ROFs of 0.650 +/- 1.9%, 0.811 +/- 0.9% and 0.843 +/- 1.7% for the 5, 7.5
      and 10 mm cones, respectively, and were in excellent agreement with radiochromic
      film values (averaged for EBT1 and EBT2) of 0.645 +/- 1.4%, 0.806 +/- 1.1% and
      0.859 +/- 1.1%. Monte-Carlo calculated correction factors were applied to the RL
      readings to correct for excessive scatter due to the relatively high effective
      atomic number of Al2 O3 (Z=10.2) compared to water for the 5, 7.5 and 10 mm
      cones. When these corrections are applied to our RL detector measurements, we
      obtain ROFs of 0.656 +/- 0.3% and 0.815 +/- 0.3% and 0.865 +/- 0.3% for 5, 7.5
      and 10 mm cones. Our study shows that the microMOSFET/RADPOS and optical fiber
      coupled RL dosimetry system are well suited for Cyberknife cone output factors
      measurements over the entire range of field sizes, provided that appropriate
      correction factors are applied for the smallest cone sizes (5, 7.5 and 10 mm).

PMID- 28516659
TI  - Sci-Sat AM: Brachy - 06: Monte carlo DNA damage simulations of kV cbct radiation.
AB  - When performed daily, cone beam CT (CBCT) images can accumulate radiation dose to
      non-negligible levels. Because kV x-rays have a larger relative biological
      effectiveness (RBE) than its MV x-rays, the accumulated absorbed dose needs to be
      multiplied by an appropriate RBE to better evaluate the impact of CBCT dose in a
      treatment planning context. We investigated this question using PENLEOPE
      simulations to look in detail at the electron energy spectra produced by kV x
      rays and Co-60 gamma-rays in biologically motivated geometries. The electron
      spectra were input into the published Monte Carlo Damage Simulation (MCDS) and
      used to estimate the average number of double strand breaks (DSBs) per Gy per
      cell. Our results suggest an approximately 10% increase in the RBE for DSB
      induction. For the majority of treatment planning scenarios where imaging dose is
      only a small fraction of the total delivered dose to target volumes and organs at
      risk, the increase in RBE is not critical to be factored in, however for it may
      play a significant role in predicting the induction of secondary cancers.

PMID- 28516661
TI  - Sci-Fri PM: Delivery - 11: Accuracy considerations in modern radiation oncology:
      An update.
AB  - The most recent reviews of accuracy requirements in radiation oncology were
      published in the 1990s, primarily in an era that was transitioning from 2-D to 3
      D conformal radiation therapy (CRT). Since then, the technology associated with
      radiation oncology has changed dramatically. The combination of various forms of
      imaging for radiation therapy planning, treatment planning software, dose
      delivery technology including 4-D considerations as well as in-room daily image
      guidance has resulted in new perspectives on accuracy considerations. The
      underlying hypothesis for the use of these advanced technologies is that loco
      regional control of cancer remains a significant barrier to cancer cure for many
      common cancers and that better dose distributions will translate into better
      outcomes. However, further clinical gain using these new technologies may be
      limited by single or compounded uncertainties associated with the entire
      treatment process. Thus, it is important to understand what factors should be
      considered in determining accuracy requirements as well as the realistic
      expectations of uncertainties that exist within the total treatment process. The
      need for accuracy is based on clinical requirements such as the steepness of dose
      response curves, inherent heterogeneity in patient response to treatment, and the
      level of accuracy that is practically achievable. Statements on accuracy are
      dependent on the technology used and the reality of what is practically
      achievable and necessary. This review highlights some of the major differences
      between accuracy requirements as determined in the 2-D RT and 3-D CRT era versus
      the modern era of intensity modulated, image-guided, 4-D radiation therapy.

PMID- 28516660
TI  - Sci-Fri AM: Imaging - 04: SPECT-based functional lung imaging in the prediction
      of radiation pneumonitis: A retrospective clinical and dosimetric correlation.
AB  - PURPOSE: To investigate whether functionally-weighted dose-volume histogram (DVH)
      parameters are more predictive of radiation-induced pneumonitis (RP) than
      standard parameters such as V20 and mean lung dose (MLD). MATERIALS AND METHODS:
      A retrospective chart review identified 26 patients who received curative-intent
      radiation therapy for primary carcinoma of the lung. Prior to treatment, all
      patients received single photon emission computed tomography (SPECT) to assess
      both lung ventilation and lung perfusion. Patients were assessed for clinical RP
      using standard criteria and were separated into a non-RP group (RP grade < 2) and
      an RP-group (RP grade >= 2). Standard DVH parameters (V10, V20, V30, MLD) and
      their function-weighted counterparts (for perfusion: pF10, pF20, pF30, pMLD; for
      ventilation: vF10, vF20, vF30, vMLD) were evaluated for each group. Receiver
      operating characteristics (ROC) curves were created and the area under the curve
      (AUC) computed. RESULTS: 7 of 26 patients had grade >= 2 pneumonitis. Both pF20
      (p=0.022) and vF20 (p=0.036) were significantly different between the 2 groups;
      V20 was not (p=0.06). Both pF30 (p=0.008) and vF30 (p=0.025) were significantly
      different between groups while V30 failed to reach significance (p=0.072).
      Standard MLD (p=0.011), pMLD (p=0.001), and vMLD (p=0.011) were all significantly
      different. The ROC curves indicated that both the perfusion-weighted parameters
      and the ventilation-weighted parameters outperformed the standard DVH parameters
      as predictors of RP grade >=2. CONCLUSIONS: SPECT-based, function-weighted DVH
      parameters appear to be useful as predictors of RP.

PMID- 28516662
TI  - Sci-Sat AM: Brachy - 10: Adaptation of the CVT algorithm for catheter
      optimization in high dose rate brachytherapy.
AB  - INTRODUCTION: In interstitial high dose rate (HDR) brachytherapy, the number and
      positions of the catheter are usually fixed by the use of a template, without
      considering tumor size and shape. In this work, we present a simple and fast
      method to optimize both the number and position of catheters, using a modified
      version of the Centroidal Voronoi Tessellations (CVT) algorithm. METHODS: 8
      prostate HDR clinical cases were chosen randomly to test our method. The
      treatment plan was obtained from a research version of IPSA. Clinically relevant
      dosimetric parameters were computed to evaluate our method and help optimizing
      the CVT algorithm parameters. Plans were generated with a specified number of
      catheters ranging from 9 to 18 and compared to the clinical cases with 17
      catheters. RESULTS: The computation time to optimize the positions of a specific
      number of catheters was 1.5 s. The prostate V100 was better than the clinical
      case up to 12 catheters. Plans with 9 or less catheters would not be clinically
      acceptable in terms of prostate V100 and D90. High conformity is achieved whether
      the number of catheters used. The V75 of the bladder seems slightly higher, but
      not significant clinically. All other dosimetric indices are as good as the
      clinical plan. CONCLUSION: We have devised a simple, fast and efficient method to
      optimize the number and position of catheters in HDR brachytherapy. Ultimately,
      this catheter optimization algorithm could be coupled with a 3D ultrasound system
      to allow real-time guidance and planning for any interstitial brachytherapy
      sites.

PMID- 28516663
TI  - Poster - Thur Eve - 74: A set of tests designed for electron dose calculation
      algorithm verification during a treatment planning system upgrade.
AB  - A set of tests were designed to verify an electron algorithm effectively and
      quickly during a treatment planning system upgrade. Based on TG-53 report's
      suggestion and the assumption that the algorithm is well commissioned before the
      upgrade, the tests spot-check the output factors, depth doses, off-axis doses and
      treatment field sizes. The field sizes of 4*4, 6*6, 10*10, 15*15, 20*20 and 25*25
      are to be tested. Four test plans are created for each field size, i.e., for open
      field, for extended SSD, for shaped field, and for bolus field. Fixed MU setting
      is recommended to avoid a possible plan normalization issue. The parameters to be
      recorded and compared include doses at dmax , R50 and Rp along central axis,
      which contain output and depth dose information, doses at four off-axis points in
      dmax plane, which contain off-axis dose and beam symmetry information, and FWHMs
      at dmax . For the plans other than open field only doses at dmax are checked. The
      tests were performed successfully during a planning system upgrade. The whole
      test can be completed in approximately 12 hours if the workload is distributed
      into multiple task carriers. It was found that most of the data agree very well
      between the old and the new version of the algorithm while some of the Rp or R50
      doses deviated more than other data, which prompted a depth dose check. PDD
      comparisons were performed for the involved fields and it was found there were
      less than 0.5 mm PDD shifts occurred.

PMID- 28516664
TI  - Sci-Fri AM: Imaging - 08: Comparison of single and dual layer detector blocks for
      pre-clinical MRI-PET.
AB  - Our group is developing a small animal PET scanner which would fit in a 7 Tesla
      MRI scanner to provide simultaneous PET and MR acquisitions and images. There is
      very little room for the PET detectors and we must use nonmagnetic materials.
      This presentation describes preliminary work with two PET detectors consisting of
      LYSO blocks each with two crystal layers: 49 1.67*1.67*6.0 mm on the bottom layer
      and 36 4.0 mm deep crystals on the top layer. These are mounted on SensL 4*4
      arrays of silicon photo-multipliers whose outputs are multiplexed to provide
      three signals: Energy, X, Y. These detectors were mounted on translation stages
      and scanned past a 0.25 mm diameter 370 MBq Na-18 source embedded in tissue
      equivalent plastic. The results were compared with similar single layer crystal
      blocks with 10 mm deep crystals to assess the advantage of dual layer crystals to
      reduce radial blurring in a PET scanner with a diameter of only 64 mm. The
      ability to identify correctly each crystal is reported as its resolvability
      index, (RI), defined as the (crystal response FWHM)/(crystal's separation) in the
      crystal identification matrix. For the dual layer block RI =0.44, and for dual
      layer block RI=0.22. The coincidence response resolution for the single layer
      block varied from 1.23+/-0.05 mm at the centre of the scanner to 3.09+/-0.10 mm
      at 15.8 mm radius, while the dual layer block varied from 1.31+/-0.06 to 1.96+/
      0.51 mm over the same range, confirming the Monte-Carlo simulations showing
      reduced radial blurring.

PMID- 28516665
TI  - Fifty-Eighth Annual Meeting of the Canadian Organization of Medical Physicists
      and the Canadian College of Physicists in Medicine.

PMID- 28516666
TI  - Sci-Fri AM: Imaging - 01: Feasibility of estimating choline kinase activity with
      kinetic modeling of 18F-fluorocholine pet imaging of prostate cancer.
AB  - Prostate cancer (PCa) detection and delineation remains a challenge for medical
      imaging. Studies have shown 18 F-Fluorocholine (FCH) PET imaging to be a
      promising modality in the detection of recurrent PCa. Detection of denovo PCa is
      more challenging, as lesions such as benign prostatic hyperplasia (BPH) may
      adversely affect the sensitivity and specificity of the modality. PCa and BPH
      have been shown to exhibit similar uptake of FCH, yet it has been shown that
      phosphocholine levels are much more elevated in PCa compared to BPH. Therefore,
      it would be useful to measure the activity of phosphorylation via choline kinase
      (k3 ) in order to differentiate PCa from BPH. This work examines the feasibility
      of using a compartmental model to estimate k3 with dynamic 18 F-Fluorocholine PET
      imaging. JSim software [1] was used to simulate the compartmental model for FCH
      exchange. A simulated tissue curve was generated using predefined parameters and
      the model's ability to estimate these parameters through fitting of the simulated
      tissue curve with and without noise was investigated. The fitting procedure was
      performed using the non-negative least squares algorithm in MATLAB after the
      equation governing fitting was linearized. In the noiseless case, the model was
      able to accurately identify the values of each rate parameter. For the noisy case
      with an SNR of 10:1, the mean estimated k3 for 10,000 runs had a coefficient of
      variation of 14.9%. The kinetic model shows promise for quantifying k3 , which
      would allow the differentiation of malignant and benign tumours of the prostate.

PMID- 28516667
TI  - Sci-Fri PM: Delivery - 03: Spine SBRT: Treating multiple vertebrae using cone
      beam CT image-guidance and the hexapod robotic couch.
AB  - PURPOSE: The intent of spinal SBRT is to maximize the biological effective dose
      and improve local control, while sparing the adjacent spinal cord. We report on
      the spinal SBRT positional accuracy for multiple, consecutive vertebrae in a
      single course, using the Elekta Synergy-S and BodyFIX immobilization systems.
      METHODS: After initial patient adjustment, verification cone-beam CT (CBCT)
      images were acquired before, during and after treatment. These images were used
      to assess immobilization and correct any misalignment exceeding 1 mm or 1 degrees
      , in all six degrees-of-freedom using the HexaPOD robotic couch. This analysis is
      based on 415 verification images from 67 consecutive courses of treatment. These
      treatment courses comprised 25 single thoracic vertebrae, 16 multiple thoracic
      vertebrae, 20 single lumbar vertebrae and 6 multiple lumbar vertebrae. RESULTS:
      The absolute intra-fraction motion averaged over all directions (+/-std dev.) for
      the T-single, T-multiple, L-Single and L-Multiple was 0.54 (+/-0.73) mm, 0.54 (+/
      0.88) mm, 0.36 (+/-0.57) mm, and 0.47 (+/-0.63) mm respectively. The percentage
      that exceeded the 1.5 mm planning margin was 3.8%, 4.0%, 1.0% and 0.85%
      respectively. T-spine treatments were out-of-tolerance more frequently than the L
      spine. There was a statistically significant difference between single and
      multiple lumbar treatments (unpaired t-test, p<0.01), but this was not clinically
      significant as 99% were within our 1.5 mm margin. CONCLUSIONS: Near-rigid
      immobilization with the acquisition of intra-fraction CBCT images and the
      correction of misalignments in all six degrees-of-freedom provides the necessary
      precision to safely perform SBRT of consecutive spinal metastases within one
      course of treatment.

PMID- 28516668
TI  - Sci-Fri PM: Delivery - 06: A generalized solution to the wide field array
      calibration method.
AB  - Multi detector arrays are commonly used in radiation oncology for IMRT and Linac
      QA. The calibration of detector arrays is usually based on the wide field
      calibration technique. Unfortunately small beam changes between measurements will
      result in large error propagation. The present work introduces a generalized
      modified version of the wide field calibration method, robust against measurement
      to measurement variation. Our generalized framework uses an unlimited number of
      measurement pairs, n geometric positions providing n(n-1)/2 pairs. We solve this
      large over determined linear system using least squares with gradient method.
      Measurements were made on an Elekta synergy 6 MV beam with two IBA Matrixx
      detectors, each containing a 32 * 32 array (1024) of vented pixel ionization
      chambers. Data acquisition was by the IBA Omnipro Advance software, version 1.2
      running in the "ONLINE" cine mode with a 10 sec integration time. Continuous beam
      sampling (10 seconds long) measured over 10 minutes demonstrated why consistent
      calibration using the conventional wide field calibration is a challenge. Overall
      signal changes of 1.6%, flatness changes of 0.3% and the beam symmetry changes of
      0.2% over the full 10 minute beam-on time were observed. For the purpose of
      testing and demonstration of our method, we have chosen to make measurements in 5
      geometric orientations relative to the beam, including 1 reference position, 2
      rotations and 2 translations. With our method we were able to calibrate all 1024
      detectors to better than 0.6% total uncertainty as demonstrated against inter and
      intra MatriXX comparison.

PMID- 28516669
TI  - State of the Art: Novel Applications for Deep Brain Stimulation.
AB  - OBJECTIVES: Deep brain stimulation (DBS) is a rapidly developing field of
      neurosurgery with potential therapeutic applications that are relevant to
      conditions traditionally viewed as beyond the limits of neurosurgery. Our
      objective, in this review, is to highlight some of the emerging applications of
      DBS within three distinct but overlapping spheres, namely trauma,
      neuropsychiatry, and autonomic physiology. REVIEW METHODS: An extensive
      literature review was carried out in MEDLINE, to identify relevant studies and
      review articles describing applications of DBS in the areas of trauma,
      neuropsychiatry and autonomic neuroscience. RESULTS: A wide range of applications
      of DBS in these spheres was identified, some having only been tested in one or
      two cases, others much better studied. CONCLUSIONS: We have identified various
      avenues for DBS to be applied for patient benefit in cases relevant to trauma,
      neuropsychiatry and autonomic neuroscience. Further developments in DBS
      technology and clinical trial design will enable these novel applications to be
      effectively and rigorously assessed and utilized most effectively.

PMID- 28516670
TI  - Endoscopic versus open radial artery harvesting: A meta-analysis of randomized
      controlled and propensity matched studies.
AB  - BACKGROUND: We sought to investigate the impact of radial artery harvesting
      techniques on clinical outcomes using a meta-analytic approach limited to
      randomized controlled trials and propensity-matched studies for clinical
      outcomes, in which graft patency was analyzed. METHODS: A systematic literature
      review was conducted using PubMed and MEDLINE to identify publications containing
      comparisons between endoscopic radial artery harvesting (ERAH) and open
      harvesting (ORAH). Only randomized controlled trials and propensity-matched
      series were included. Data were extracted and analyzed with RevMan. The primary
      endpoint was wound complication rate, while secondary endpoints were patency
      rate, early mortality, and long-term cardiac mortality. RESULTS: Six studies
      comprising 743 patients were included in the meta-analysis. Of them 324 (43.6%)
      underwent ERAH and 419 (56.4%) ORAH. ERAH was associated with a lower incidence
      of wound complications (odds ratio: 0.33, confidence interval 0.14-0.77; p =
      0.01). There were no differences in graft patency, and early and long-term
      cardiac mortality between the two techniques. CONCLUSION: ERAH reduces wound
      complications and does not affect graft patency, or short- and long-term
      mortality compared to ORAH.

PMID- 28516671
TI  - The aggressive peripheral T-cell lymphomas: 2017.
AB  - BACKGROUND: T-cell lymphomas make up approximately 10%-15% of lymphoid
      malignancies. The frequency of these lymphomas varies geographically, with the
      highest incidence in parts of Asia. DIAGNOSIS: The diagnosis of aggressive
      peripheral T-cell lymphoma (PTCL) is usually made using the World Health
      Organization classification. The ability of hematopathologists to reproducibly
      diagnose aggressive PTCL is lower than that for aggressive B-cell lymphomas, with
      a range of 72%-97% for the aggressive PTCLs. Risk Stratification: Patients with
      aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat
      controversial, positron emission tomography scans seem to be useful as they are
      in aggressive B-cell lymphomas. The specific subtype of aggressive PTCL is an
      important risk factor with the best survival seen in anaplastic large-cell
      lymphoma-particularly young patients with the anaplastic lymphoma kinase positive
      subtype. RISK-ADAPTED THERAPY: Anaplastic large-cell lymphoma is the only
      subgroup to have a good response to a CHOP-like regimen. Angioimmunoblastic T
      cell lymphoma has a prolonged disease-free survival in only ~20% of patients, but
      younger patients who have an autotransplant in remission seem to do better. PTCL
      not otherwise specified is not one disease. Anthracycline-containing regimens
      have disappointing results, and a new approach is needed. Natural killer/T-cell
      lymphoma localized to the nose and nasal sinuses seems to be best treated with
      radiotherapy-containing regimens and the majority of patients are cured.
      Enteropathy-associated PTCL and hepatosplenic PTCL are rare disorders with a
      generally poor response to therapy although selected patients with enteropathy-
      associated PTCL seem to benefit from intensive therapy.

PMID- 28516672
TI  - Two-photon imaging of fiber-coupled neurons.
AB  - Optical coupling between a single, individually addressable neuron and a properly
      designed optical fiber is demonstrated. Two-photon imaging is shown to enable a
      quantitative in situ analysis of such fiber-single-neuron coupling in the live
      brain of transgenic mice. Fiber-optic interrogation of single pyramidal neurons
      in mouse brain cortex is performed with the positioning of the fiber probe
      relative to the neuron accurately mapped by means of two-photon imaging. These
      results pave the way for fiber-optic interfaces to single neurons for a
      stimulation and interrogation of individually addressable brain cells in chronic
      in vivo studies on freely behaving transgenic animal models, as well as the
      integration of fiber-optic single-neuron stimulation into the optical imaging
      framework.

PMID- 28516673
TI  - Choice among two and three alternatives.
AB  - Although choice between two alternatives has been widely researched, fewer
      studies have examined choice across multiple (more than two) alternatives. Past
      models of choice behavior predict that the number of alternatives should not
      affect relative response allocation, but more recent research has found
      violations of this principle. Five pigeons were presented with three concurrently
      scheduled alternatives. Relative reinforcement rates across these alternatives
      were assigned 9:3:1. In some conditions three keys were available; in others,
      only two keys were available. The number of available alternatives did not affect
      relative response rates for pairs of alternatives; there were no significant
      differences in behavior between the two and three key conditions. For two birds
      in the three-alternative conditions and three birds in the two-alternative
      conditions, preference was more extreme for the pair of alternatives with the
      lower overall pairwise reinforcer rate (3:1) than the pair with higher overall
      reinforcer rate (9:3). However, when responding during the changeover was removed
      three birds showed the opposite pattern in the three-alternative conditions;
      preference was more extreme for the pair of alternatives with the higher overall
      reinforcer rate. These findings differ from past research and do not support
      established theories of choice behavior.

PMID- 28516674
TI  - Selection by consequences, behavioral evolution, and the price equation.
AB  - Price's equation describes evolution across time in simple mathematical terms.
      Although it is not a theory, but a derived identity, it is useful as an
      analytical tool. It affords lucid descriptions of genetic evolution, cultural
      evolution, and behavioral evolution (often called "selection by consequences") at
      different levels (e.g., individual vs. group) and at different time scales (local
      and extended). The importance of the Price equation for behavior analysis lies in
      its ability to precisely restate selection by consequences, thereby restating, or
      even replacing, the law of effect. Beyond this, the equation may be useful
      whenever one regards ontogenetic behavioral change as evolutionary change,
      because it describes evolutionary change in abstract, general terms. As an
      analytical tool, the behavioral Price equation is an excellent aid in
      understanding how behavior changes within organisms' lifetimes. For example, it
      illuminates evolution of response rate, analyses of choice in concurrent
      schedules, negative contingencies, and dilemmas of self-control.

PMID- 28516676
TI  - Retention of pigment stem cells in Rhododenol-induced leukoderma: Pathological
      investigation of 11 patients.

PMID- 28516677
TI  - Poster - Thur Eve - 42: Dynamic delivery quality assurance on Elekta linacs.
AB  - Introduction Recently, Elekta linacs have gained the capability to deliver
      dynamic fields, such as sliding window IMRT or VMAT fields. Because of the
      potential complexity of such delivery modes, linac QA and patient-specific QA are
      of prime importance. The aim of this paper is to explain the fundamental concepts
      of this new mode of operation on Elekta linacs as well as to introduce the linear
      alpha slit, a novel dynamic QA sequence which allows the performance of the
      delivery system to be objectively aassessed against dosimetric measurements. In
      the Elekta dynamic mode, dose rate can only take a limited number of
      discontinuous values. We have used the uniform slit, a simple slit moving at a
      constant speed across the field to verify how the linac selects leaf speed and
      dose rate for a given MU setting. Based on this, we expose the principles behind
      the linear-alpha slit, which exhibits two main characteristics: 1) it exercises
      the linac over a range of dose rates and 2) it produces a dose distribution which
      is theoretically equivalent to the uniform slit. Discrepancies between
      measurements of the linear-alpha slit and the uniform slit directly reflects
      problems with the delivery. The linear-alpha slit has been recently introduced in
      our routine monthly linac QA. We hope it will nicely complement patient-specific
      QA, and exising linac-QA.

PMID- 28516675
TI  - Analysis of platelet-reactive alloantibodies and evaluation of cross-match
      compatible platelets for the management of patients with transfusion
      refractoriness.
AB  - BACKGROUND: Cross-match-compatible platelets can improve corrected count
      increments (CCIs) in alloimmunised patients with transfusion refractoriness.
      However, only a few studies mentioned that the specificities of platelet-reactive
      alloantibodies can predict high reactivity in cross-match assays among these
      patients. METHODS: A total of 204 medical records of patients who were refractory
      to random single-donor apheresis platelets between January 2014 and December 2014
      were enrolled. Platelet-reactive antibodies in patients' serum were screened by
      an enzyme-linked immunosorbent assay (ELISA).The platelet cross-match assays were
      performed by a solid-phase adherence assay. The specificities of human leukocyte
      antigen (HLA) class I and human platelet antigens (HPAs) alloantibodies were
      determined by Luminex Single Antigen and Monoclonal Antibody-specific
      Immobilization of Platelet Antigens (MAIPA) assays, respectively. RESULTS: Anti
      HLA and anti-HPA alloantibodies were found in 114 of 204 (55.88%) patients,
      including 110 (96.49%) with anti-HLA alloantibodies only, 2 (1.75%) with anti-HPA
      alloantibodies (anti-GPIIb/IIIa) only and 2 (1.75%) with both anti-HLA and anti
      HPA alloantibodies (anti-HPA-3a and anti-HPA-5b). The most common HLA class I
      alloantibody phenotypes in cross-match-incompatible patients were HLA-A23
      (59.38%), -A24 (50.00%), -A02 (43.75%), -B27 (65.63%), -B40 (50.00%), -B18
      (46.88%) and -B07 (43.75%). A total of 480 cross-matched platelet units were
      administered in 82 of 114 alloimmunised patients with a mean CCI of 7800 +/-
      5200, a significant improvement over random platelet units (P < 0.001).
      CONCLUSIONS: No development of additional platelet alloantibodies was observed
      during this platelet transfusion regiment. This study showed that transfusion of
      cross-match-compatible platelet units offers effective and safe management of
      platelet transfusion refractoriness (PTR). The finding of alloantibodies among
      cross-match-incompatible cases can be used as predictors for platelet donor
      selection.

PMID- 28516678
TI  - Poster - Thur Eve - 53: Analysis of the distribution of dose delivery during
      respiratory-gated step-and-shoot IMRT for lung cancer radiotherapy.
AB  - Respiratory motion is a large source of dosimetric error when treating lung
      cancer with Intensity Modulated Radiation Therapy (IMRT). The asynchronicity of
      the tumour motion and the multileaf collimator (MLC) used to modulate the
      radiation beam intensity, leads to the interplay effect. One method to account
      for this effect is respiratory gating. Treatment planning optimization for gated
      IMRT is performed on a subset average 4D-CT which includes the phases surrounding
      end exhalation. However, this assumes that the beam delivery will be evenly
      distributed amongst those phases. This study investigates the distribution of
      beam delivery during gated step-and-shoot IMRT (SS-IMRT) for both early and late
      stage non-small cell lung cancer (NSCLC). Four Stage I NSCLC patients, prescribed
      a dose of 54 Gy in 3 fractions, and five Stage III NSCLC patients, prescribed a
      dose of 60 Gy in 30 fractions, were retrospectively planned with high and low
      modulation beams-IMRT, and delivered using the QUASARTM Programmable Respiratory
      Motion Platform with 15 mm and 20 mm peak-to-peak sinusoidal motion and real
      patient breathing motion. The percent monitor units delivered at each phase were
      compared. For Stage I patients, the monitor units delivered were evenly
      distributed over the gating window due to a high number of monitor units
      delivered per control point. For Stage III patients, as the complexity of SS-IMRT
      increases, there were more monitor units delivered in the initial gating phase.
      This dose discrepancy could potentially lead to geographic miss of the tumour and
      should be taken into account during treatment planning.

PMID- 28516679
TI  - Poster - Thur Eve - 24: Clinical application of the new dosimetry formalism for
      composite nonstandard beams.
AB  - The IAEA-AAPM new dosimetry formalism [Med. Phys. 35, 5179 (2008)] was applied to
      clinical IMRT quality assurance (QA). Twenty different IMRT QA fields were
      created on the CT images of a 30*30*17 cm3 Solid WaterTM phantom. Two Farmer-type
      chambers, Exradin A12 and NE2571, and a smaller Exradin A1SL ionization chamber
      were cross-calibrated against a reference detector, the PTW micro liquid ion
      chamber (microLion), in the lowest dose gradient region in each IMRT QA field
      delivery. Based on the new dosimetry formalism, the clinical correction factor
      was measured in a fully-rotated delivery and a delivery at a single gantry angle,
      a collapsed delivery. For the calibrated Exradin A12, the measured dose with the
      clinical correction factor was compared with a calculated dose using Monte Carlo
      (MC) methods. The clinical correction factor deviated from unity by up to 2.4%
      and 3.7% in the fully-rotated and collapsed deliveries, respectively, depending
      on the dose distribution in the chamber collecting volume. For the Exradin A1SL,
      the correction factor was generally closer to unity due to the reduced dose
      gradient on the smaller collecting volume. In the fully-rotated delivery, the
      measured dose with the clinical correction factor is different from the MC
      calculated dose to within 4%; while the discrepancy was greater, up to 8%, in the
      collapsed delivery due to the much heterogeneous dose distribution in the chamber
      collecting volume. This work proves that the suggested dosimetry technique is
      effective to improve the dosimetric consistency of clinical IMRT QA.

PMID- 28516681
TI  - Poster - Thur Eve - 35: Characterization of performance of two deformable
      registration software.
AB  - PURPOSE: To evaluate the performance of two deformable registration softwares (a
      commercial and an open source software) using cone-beam computed tomography
      (CBCT) images. METHODS: We used a set of 34 lung patients with generally large
      tumors each having between 1 and 20 CBCT scans. A radiation oncologist resident
      contoured GTVs on each CBCTs using planning CT contours as reference. Deformable
      registrations were performed on CT scans to adapt it to the first CBCT of each
      patient independently with both software. Then each CBCT was registered to the
      next CBCT. Contour structures have been deformed in the process for the
      commercial software and for the open source software contours have been drawn
      manually on deformed images. RESULTS: Mean remaining volume (+/-SD) for manual
      GTV contours was 59 +/- 32 %. GTVs obtained with the open source software were
      closer to the manual GTV in size than the commercial software. Mean relative
      errors on volume were 45 +/- 60 % for the commercial system (33 patients) and 9
      +/- 2 % for the open source software (6 patients). Relative errors for the
      commercial software increased exponentially with the volume reduction but were
      constant over all CBCT for the open source software. Mean Jaccard and Dice's
      index were 0.57 and 0.71 for the commercial software (24 patients) and 0.80 and
      0.88 for the open source software (6 patients). CONCLUSION: Open source software
      shown tendency to give better results than commercial software but was slower
      than the commercial software.

PMID- 28516680
TI  - Poster - Thur Eve - 64: Evaluation of SmartArc and RapidArc for lung SBRT
      treatment planning and delivery.
AB  - OBJECTIVES: To evaluate the performance of RapidArc(r) (Eclipse 10.0.28) and
      SmartArc(r) (Pinnacle 9.0) radiotherapy plans for lung stereotactic body
      radiation therapy (SBRT) in terms of dosimetric plan quality, delivery
      efficiency, inhomogeneity corrections and accuracy of dose delivery using a
      custom-built heterogeneity insert for ArcCHECKTM (Sun Nuclear Corp., FL, USA).
      METHODS: SmartArc(r) and RapidArc(r) plans were generated for 10 patients. The
      quality of the plans was evaluated in terms of conformity indices (R100 and R50 )
      and the dose to the organs at risk. The efficiency was evaluated in terms of the
      monitor units (MUs) required for a given prescription dose. For dose
      verification, we designed and manufactured a heterogeneity insert for ArcCHECKTM
      with densities that simulate soft tissue, lung, bone, and air and having multiple
      locations for point dose measurements. Accuracy of dose delivery was assessed
      using gamma analysis. RESULTS: The overall plan quality was similar when
      comparing SmartArc(r) with RapidArc(r). However, RapidArc(r) plans required
      significantly more MUs-up to 72%TMcompared with SmartArc(r) plans (p<0.001).
      ArcCHECKTM measurements in the presence of inhomogeneities showed better
      agreement for SmartArc(r) plans. CONCLUSION: Plan quality for SmartArc(r) and
      RapidArc(r) was comparable. However, SmartArc(r) plans were more efficient,
      requiring significantly fewer monitor units, and were delivered more accurately
      in a non-homogeneous phantom. With the custom-built heterogeneity insert,
      ArcCHECKTM can be used efficiently to verify inhomogeneity corrections and dose
      delivery accuracy for lung SBRT plans.

PMID- 28516682
TI  - Poster - Thur Eve - 46: The upcoming international code of practice for small
      static photon field dosimetry.
AB  - The increased use of small photon fields in stereotactic and intensity-modulated
      radiotherapy has raised the need for standardizing the dosimetry of such fields
      using procedures consistent with those for conventional radiotherapy. An
      international working group, established by the IAEA in collaboration with AAPM
      and IPEM, is finalising a Code of Practice for the dosimetry of small static
      photon fields. Procedures for reference dosimetry in nonstandard machine specific
      reference (msr) fields are provided following the formalism of Alfonso et al.
      (Med. Phys. 35: 5179; 2008). Reference dosimetry using ionization chambers in
      machines that cannot establish a conventional 10 cm * 10 cm reference field is
      based on either a direct calibration in the msr field traceable to primary
      standards, a calibration in a reference field and a generic correction factor or
      the product of a correction factor for a virtual reference field and a correction
      factor for the difference between the msr and virtual fields. For the latter
      method, procedures are provided for determining the beam quality in non-reference
      conditions. For the measurement of field output factors in small fields,
      procedures for connecting large field measurements using ionization chambers to
      small field measurements using high-resolution detectors such as diodes, diamond,
      liquid ion chambers, organic scintillators and radiochromic film are given. The
      Code of Practice also presents consensus data on correction factors for use in
      conjunction with measured, detector-specific output factors. Further research to
      determine missing data according to the proposed framework will be strongly
      encouraged by publication of this document.

PMID- 28516684
TI  - Poster - Thur Eve - 28: Optimization of a prostate cancer IGRT protocol.
AB  - Our image-guided radiation therapy (IGRT) protocol for post-prostatectomy
      patients involves acquiring a kV cone beam computed tomography (CBCT) dataset at
      each fraction and shifting the treatment couch to align the surgical clips. This
      IGRT strategy requires significant resources, and delivers non-negligible dose to
      normal tissues. The objective of this work is to evaluate this IGRT protocol
      against two alternative strategies in terms of the dose-volume statistics for
      target and organ at risk regions. Our method involves deforming the planning CT
      to the CBCT dataset acquired at each fraction, computing dose on the deformed
      dataset, and inversely transforming the dose back onto the original planning CT
      dataset. The treatments of six patients were evaluated assuming three IGRT
      scenarios: no IGRT, daily IGRT using the clinically employed couch shifts, and
      alternating day IGRT. The doses delivered to the clinical target volumes are
      within approximately 3.2, 1.3, and 2.1% of the plan for the non-IGRT, daily, and
      alternating day IGRT protocols, respectively. Doses to relevant portions of the
      organs at risk deviate from the plan by up to 10.5, 13.1 and 10.7% for non-IGRT,
      daily IGRT, and alternating day IGRT protocols, respectively. Some cases do not
      differ significantly between IGRT and non-IGRT protocols in terms of cumulative
      DVHs, highlighting the difficult task of correcting prostate bed deformations via
      the treatment couch translations. In general, the alternating day IGRT protocol
      was found to result in a clinically insignificant deviation in delivered dose
      while providing a significant reduction in resource use and patient imaging dose.

PMID- 28516683
TI  - Poster - Thur Eve - 57: Craniospinal irradiation with jagged-junction IMRT
      approach without beam edge matching for field junctions.
AB  - PURPOSE: Craniospinal irradiation were traditionally treated the central nervous
      system using two or three adjacent field sets. A intensity-modulated radiotherapy
      (IMRT) plan (Jagged-Junction IMRT) which overcomes problems associated with field
      junctions and beam edge matching, improves planning and treatment setup
      efficiencies with homogenous target dose distribution was developed. METHODS AND
      MATERIALS: Jagged-Junction IMRT was retrospectively planned on three patients
      with prescription of 36 Gy in 20 fractions and compared to conventional treatment
      plans. Planning target volume (PTV) included the whole brain and spinal canal to
      the S3 vertebral level. The plan employed three field sets, each with a unique
      isocentre. One field set with seven fields treated the cranium. Two field sets
      treated the spine, each set using three fields. Fields from adjacent sets were
      overlapped and the optimization process smoothly integrated the dose inside the
      overlapped junction. RESULTS: For the Jagged-Junction IMRT plans vs conventional
      technique, average homogeneity index equaled 0.08+/-0.01 vs 0.12+/-0.02, and
      conformity number equaled 0.79+/-0.01 vs 0.47+/-0.12. The 95% isodose surface
      covered (99.5+/-0.3)% of the PTV vs (98.1+/-2.0)%. Both Jagged-Junction IMRT
      plans and the conventional plans had good sparing of the organs at risk.
      CONCLUSIONS: Jagged-Junction IMRT planning provided good dose homogeneity and
      conformity to the target while maintaining a low dose to the organs at risk.
      Jagged-Junction IMRT optimization smoothly distributed dose in the junction
      between field sets. Since there was no beam matching, this treatment technique is
      less likely to produce hot or cold spots at the junction in contrast to
      conventional techniques.

PMID- 28516685
TI  - Poster - Thur Eve - 39: SBRT imaging analysis - patient results and QA of imaging
      systems.
AB  - Our centre began offering stereotactic body radiation therapy (SBRT) treatments
      for peripheral lung lesions in 2011. As a high-precision technique, SBRT requires
      precise positioning of the target, and precise quality assurance (QA) of the
      imaging systems; these may be dependent on local equipment and procedures. We
      aimed to maintain target position within 3 mm throughout each treatment, and
      imaging and mechanical systems to at least 2 mm accuracy. A retrospective
      analysis was done of patient cone-beam (CB) data, and of our imaging system QA,
      to assess our spatial objectives and look for opportunities for improvement. The
      data indicated that, using our immobilization and imaging procedures, target
      position was maintained within 3 mm 96% of the time, and 75% within 2 mm, similar
      to results from other centres. Imaging system QA using the standard ball-bearing
      test showed system accuracy was maintained well within 1 mm. These results were
      compared with a simpler daily QA procedure using a Pentaguide phantom. The mean
      and standard deviation of the radial difference in the kV-MV isocenter
      coincidence for the two techniques was 0.62mm +/- 0.23mm. With appropriate choice
      of tolerance and action level, the morning QA was sufficient for identifying
      outliers requiring further investigation. This analysis gives us confidence in
      understanding the performance of our SBRT lung treatments, and gives baselines
      for analyzing changes to patient immobilization or imaging procedures.

PMID- 28516686
TI  - Poster - Thur Eve - 50: Planning and delivery accuracy of stereotactic
      radiosurgery with Tomotherapy as compared to linear-accelerator and robotic based
      radiosurgery.
AB  - This study includes planning and delivery comparison of three stereotactic
      radiosurgery techniques : Helical Tomotherapy (HT), circular collimator-based
      Linear-accelerator and robotic-radiosurgery. Plans were generated for two
      spherical targets of diameter 6 mm and 10 mm contoured at the center of a Lucite
      phantom, using similar planning constrains. Planning comparison showed that
      average conformality (0-1best) for Linear-accelerator, robotic-radiosurgery and
      HT was 1.43, 1.24, and 1.77 and gradient index (less is better) was 2.72, 4.50
      and 13.56 respectively. For delivery comparison, plans were delivered to
      radiochromic film and measured dose was compared with the planned dose. For
      Linear-accelerator and robotic-radiosurgery more than 99% pixels-passing a gamma
      criteria of 3% dose difference and 1 mm distance to agreement where as for HT
      this value was as low as 40% for off-axis targets. Further investigation of the
      delivery accuracy as a function of the location of the target with in the bore
      was initiated using small volume A1SL (0.057 cm3 ) and MicroLion liquid ion
      chamber (0.0017 cm3 ). Point dose measurements for targets located at the center
      and 10 cm away from the center of the bore showed that delivered dose varied by
      more than 15% for targets placed away from the center of the bore as opposed to
      at the center. In conclusion, Linear-accelerator and the robotic-radiosurgery
      techniques showed preferable gradient and conformality. For HT, point dose
      measurements were significantly lower than predicted by the TPS when the target
      was positioned away from the isocenter, while they were found to be higher at
      isocenter.

PMID- 28516687
TI  - Poster - Thur Eve - 21: ROC analysis in patient specific quality assurance.
AB  - INTRODUCTION: Many institutions rely on a patient specific measurement for
      IMRT/VMAT patient QA. In diagnostic imaging, radiologists use Receiver Operator
      Curves (ROC) to help quantify the value of a diagnostic imaging test. The purpose
      of this work is to investigate the value or ROC methodology for patient specific
      IMRT QA. METHODS AND MATERIALS: Beam fluences for 34 prostate IMRT patients were
      analyzed using gamma analysis. For half of these, measurements were done using
      the planned beam fluences. For the rest, perturbations to the MLC leaf positions
      were introduced. Gamma analysis was then used to measure fluence differences.
      Assuming that the unperturbed fluencies were positive measurements, distributions
      of true positive and false negatives were calculated. RESULTS: For poorly
      performing beam delivery systems the choice of gamma-DTA criterion has little
      effect on test sensitivity and specificity. The AUC is increased by about 10% for
      high performance beam delivery systems. For a 3%/3mm gamma-DTA condition, ideal
      cut off values are reasonably independent of MLC performance. At a tighter gamma
      DTA condition of 2%/2mm, then the optimal sensitivity and specificity of the test
      is more dependent on MLC performance. DISCUSSION: For a pass-fail test such as
      the gamma-DTA map is, it is important to choose an optimal cut off value to
      maximize the sensitivity and specificity of the test. ROC methodology allows
      users to follow a prescriptive method to obtain ideal cut-off values for gamma
      analysis, and to assess improvements in sensitivity and specificity for higher
      performing beam delivery system.

PMID- 28516688
TI  - Poster - Thur Eve - 61: A dosimetric comparison between single-arc and double-arc
      prostate VMAT plans.
AB  - This study compared the dosimetry between prostate plans using the single-arc and
      double-arc technique in volumetric modulated arc therapy (VMAT). Single-arc and
      double-arc prostate VMAT plans were created in five patients with prostate
      volumes ranging from 39.0-68.1 cm3 . 6 MV photon beams generated by a Varian 21EX
      linac with 120-leaf multileaf collimator, and prescription dose of 78 Gy with 39
      fractions were used. Dose-volume histograms of the target and critical organs,
      dose criteria such as the planning target volume (PTV) D99%, rectum D30% and
      rectum D50%, and dose profiles along the anterior-posterior and lateral
      directions crossing the isocenter were determined using the Eclipse treatment
      planning system with RapidArc optimization. It is found that the double-arc
      technique provided a better PTV coverage and rectal sparing compared to the
      single-arc for all patients. For dose profiles crossing the isocenter, it is seen
      that the dose in the anterior-posterior direction was shifted to the lateral,
      when the single-arc technique was replaced by the double-arc. This dosimetric
      change made the dose in the rectal position shift laterally to the femoral head,
      resulting in a lower rectal dose. The calculated monitor units (MUs) were 471-600
      for the single-arc plans and 587-730 for the double-arc. Although the double-arc
      plans on average required more MUs of about 20%, and almost twice the treatment
      time compared to the single-arc, it is worthwhile to be considered particularly
      in some cases, where the dose criteria are difficult to achieve using the single
      arc technique.

PMID- 28516689
TI  - Poster - Thur Eve - 52: Clinical use of nanoDots: In-vivo dosimetry and treatment
      validation for stereotactic targets with VMAT techniques.
AB  - A newly acquired nanoDot In-Light system was compared with TLD-100 dosimeters to
      confirm the treatment dose in the multiple cases: an electron eye treatment, H&N
      IMRT and VMAT validation for small targets. Eye tumour treatment with 9 MeV
      electrons A dose of 1.8 Gy per fraction was prescribed to the 85% isodose. The
      average dose measured by three TLDs and three Dots was 1.90 and 1.97 Gy. Both
      detectors overestimated dose, by 2.9% and 6.7% respectively. H&N IMRT treatment
      of skin cancer with 6 MV photons Dose per fraction is 2.5 Gy. The average doses
      measured by two TLDs and two Dots were 2.48 and 2.56 Gy, which represent errors
      of -0.8% and 2.2%, respectively. VMAT validation for small targets using an
      Agarose phantom, dose 15 Gy A single-tumour brain treatment was delivered using
      two coplanar arcs to an Agarise phantom containing a large plastic insert holding
      3 nanoDots and 4 TLDs. The difference between the average Pinnacle dose and the
      average dose of the corresponding detectors was -0.6% for Dots and -1.7% for
      TLDs. A two-tumour brain treatment was delivered using three non-coplanar arcs.
      Small and large plastic inserts separated by 5 cm were used to validate the dose.
      The difference between the average Pinnacle dose and the average dose of the
      corresponding detectors was the following; small phantom 0.7% for Dots and 0.3%
      for TLDs, large phantom-1.9% for Dots and -0.6% for TLDs. In conclusion, nanoDot
      detectors are suitable for in-vivo dosimetry with photon and electron beams.

PMID- 28516690
TI  - Poster - Thur Eve - 23: Statistical analysis and verification of the percentage
      depth dose calculation based on the tissue maximum ratio in external beam
      radiotherapy.
AB  - The aim of this study is to perform a statistical analysis to verify the
      calculated percentage depth dose (PDD) based on the tissue maximum ratio (TMR)
      with the PDD measurements taken in water. 6 and 15 MV photon beams produced by a
      Varian linear 2100 C/D accelerator were used. PDDs and TMRs were measured at
      various depths and field sizes (5 * 5, 10 * 10, 15 * 15, 20 * 20 and 30 * 30 cm2
      ) using a PTW 31006 ionization chamber and a scanning water tank. By comparing
      the calculated and measured PDD results, it was seen that for larger field sizes
      the deviation between the calculated and measured PDD was smaller. Deviations
      between the calculated and measured results were found to be higher in the build
      up regions of the 6 and 15 MV photon beams. For the statistical analyses, t-tests
      were performed using the measured and calculated PDDs for each field size but
      showed insignificant deviations for the 6 and 15 MV photon beams. The mean t-test
      values are 0.952 and 0.970 for the 6 and 15 MV photon beams, respectively. The
      difference between the calculated and measured PDD is within the acceptable range
      according to the ICRU reports (ICRU Report No. 24, 1976). We conclude that
      accurate calculation of the PDD using the measured TMR data is possible, which is
      useful as the PDD cannot be measured directly.

PMID- 28516691
TI  - Poster - Thur Eve - 63: Dosimetric impact of breathing motion in lung SBRT: Dual
      vs single volumetric modulated arc therapy.
AB  - Volumetric modulated arc therapy (VMAT) is a time efficient treatment delivery
      platform capable of producing highly conformal dose distributions with a single
      360 degrees  arc. However, additional arcs can be used to further improve the
      conformal dose distribution. For these reasons, VMAT is often used for
      stereotactic body radiation therapy (SBRT) in which the treatment deliveries are
      hypofractionated. The dosimetric impact of tumour motion, especially in lung SBRT
      where tumour motion is most significant and treatments are hypofractionated, has
      always been a clinical concern. Through the use of 4-dimensional computed
      tomography (4D-CT), 4D dose distributions can be calculated that account for
      dosimetric errors due to motion and temporal variation in lung density that are
      not accounted for in clinical treatment plans. The purpose of this study was to
      quantify the dosimetric differences that arise due to tumour motion and
      variations in lung density between single and dual VMAT SBRT treatment plans. Six
      patients previously treated for stage I/II non-small-cell lung cancer with SBRT
      were included in this retrospective study. 3D and 4D dose distributions were
      calculated for both single and dual arc plans for each of the six patients. Dose
      volume histogram metrics are reported for the target and critical structures. The
      results show significant differences (p <= 0.05) between the 3D and 4D dose
      distributions for the ratio of the prescription isodose volume to the primary
      target volume (PTV). This result was consistent for both single and dual arc VMAT
      plans.

PMID- 28516692
TI  - Poster - Thur Eve - 34: Evaluation of 4DCT on the GE lightspeed RT16 using a
      respiratory motion phantom.
AB  - PURPOSE: This study encompasses several quality assurance tests performed during
      the commissioning of the 4DCT technique on the GE Lightspeed RT16 CT scanner for
      SBRT at the Cancer Centre of Southeastern Ontario. The main purpose is to assess
      geometric position and volumetric delineation accuracy. A limited assessment of
      the image quality and dose was performed. METHODS: The Quasar Respiratory Motion
      with a modified cylindrical moving insert was used. Clinically relevant breathing
      motion patterns analyzed were: sinusoidal with amplitudes of 5 and 15 mm, and
      periods of 3 s and 6 s; and a typical respiratory breathing motion of amplitude
      of 10 mm and period of 4 s. RESULTS: Couch position errors were <= 1mm for
      maximum inspiration (Ph 0%) and expiration (Ph 50%) phases. errors were greater
      for mid-phases, the largest being 8.1 mm (Ph 20%) for the typical respiratory
      pattern. MIP volume deviations ranged from -0.3 to -3.2 cm3 ; the greater
      deviations corresponding to larger amplitudes and shorter periods, where image
      distortion is also more severe. SUP and INF position error of MIP on coronal
      views for the lung window and level used in our centre ranged from -0.07 to 1.4
      mm and from -0.04 to 1 mm on the SUP and INF direction respectively. The dose
      from a 4DCT acquisition was 2.8 times higher than in a free breading scan, while
      the noise was comparable. CONCLUSIONS: Although higher doses are obtained, 4DCT
      is a sufficiently accurate approach that could be used safely to account for
      breathing motion.

PMID- 28516693
TI  - Poster - Thur Eve - 45: Commissioning of the Varian ECLIPSE eMC algorithm for
      clinical electron treatment planning.
AB  - Fast electron Monte Carlo systems have been developed commercially, and
      implemented for clinical practice in radiation therapy clinics. In this work the
      Varian eMC (electron Monte Carlo) algorithm was commissioned for clinical
      electron beams of energies between 6 MeV and 20 MeV. Beam outputs, PDDs and
      profiles were measured for 29 regular and irregular cutouts using the IC-10
      (Wellhofer) ionization chamber. Detailed percentage depth dose comparisons showed
      that the agreement between measurement and eMC for different characteristic
      points on the PDD are generally less than 1 mm and always less than 2 mm, with
      the eMC calculated values being lower than the measured values. Of the 145
      measured output factors, 19 cases fail a +/-2% agreement but only 8 cases fail a
      +/-3% agreement between calculation and measurement. Comparison of central axis
      dose distributions for two electron energies (9, and 20 MeV) for a 10 * 10 cm2
      field, centrally shielded with Pb of width 0 cm (open), 1, 2 and 3 cm, shows
      agreement to within 3% except near the surface. Comparison of central axis dose
      distributions for 9 MeV in heterogeneous phantoms including bone and lung inserts
      showed agreement of 1 mm and 3 mm respectively with measured TLD data. The
      overall agreement between measurement and eMC calculation has enabled us to begin
      implementing this calculation model for clinical use.

PMID- 28516694
TI  - Poster - Thur Eve - 56: Verification of buildup region dose calculation of a
      treatment planning system.
AB  - Buildup region dose calculation of Pinnacle3 (version 9.0), a treatment planning
      system (TPS) commissioned using cylindrical ionization chamber measurements, have
      been verified experimentally. Dose values measured using Attix parallel plate
      ionization chamber were compared with those calculated by Pinnacle3 for a variety
      of clinical setups involving: 6 MV and 15 MV photon beams, open fields, enhanced
      dynamic wedges, physical wedges, block tray, 85, 100 and 120 cm source-to-surface
      distances, and square field sizes ranging from 3 * 3 to 30 * 30 cm2 . The dose
      difference (DD) and distance-to-agreement (DTA) techniques were used to evaluate
      the discrepancy between measured and calculated dose values. Based on the
      criteria of DD less than 2% or DTA less than 2mm, 93.7% of 1,710 dose points for
      the 6 MV and 96.1% of 2,244 dose points for 15 MV passed. Dose points that failed
      were mostly for open fields, block tray fields, and physical wedges (15 and 30
      degrees) fields; this is attributed to high electron contamination (EC)
      associated with these fields. The levels of discrepancies between measured and
      calculated dose values were greatly reduced after remodeling the EC in Pinnacle3
      using Attix chamber measurements, an indication that the EC equation in Pinnacle3
      may be adequate for modeling EC in the dose buildup region, and the commissioning
      of a TPS using cylindrical ionization chamber measurements may not provide
      accurate buildup region dose calculation. Attix chamber measurements were
      validated using GafChromic EBT2 film; the disagreement was less than 3% for 89.9%
      of dose values compared.

PMID- 28516695
TI  - Poster - Thur Eve - 27: Scattering foil redesign for modulated electron
      radiotherapy.
AB  - This work serves to build on existing work that discussed the advantages of
      removing the scattering foil from the beamline for modulated electron
      radiotherapy (MERT) much like flattening filter-free beams in photon IMRT. Due to
      concerns about the ability of the accelerators transmission ionization chamber to
      function normally with narrow, minimally-scattered beams as well as a limited
      maximum field size, this study focused on the design of a new custom scattering
      foil that was optimized for MERT applications. Different foil parameters such as
      material, thickness and shape were investigated to produce a minimally scattered
      beam, as opposed to a flat beam in the case of the clinical foil, while
      preserving the dosimetric benefits of a reduced thickness foil such as
      dramatically higher dose rate and reduced photon contamination in the
      bremsstrahlung tail. Using a Monte Carlo model that was verified against measured
      data, fluence profiles at the level of the transmission ionization chamber were
      produced and analyzed for all foil configurations, as well as PDDs and profiles
      in a water phantom. It was found that a simple foil of slab geometry made of low
      to medium Z material with the thickness determined by the maximum desirable field
      size and chosen electron energy produced a sufficiently scattered beam that
      maintained the dosimetric advantages of a scattering-foil-free beamline. These
      new foils, when applied to MERT, have the advantage of reducing treatment time
      due to higher dose rates and reducing dose to healthy tissue due to reduced dose
      in the bremsstrahlung tail.

PMID- 28516696
TI  - Poster - Thur Eve - 38: Review of couch parameters using an FMEA.
AB  - To improve patient safety during positioning, we undertook a systematic review of
      the processes used by our center to obtain couch positions. We used a Failure
      Mode and Effects Analysis (FMEA) framework and fifteen different possible
      failures were identified and rated. The three major failures were 1) Loss of
      planned couch position and bias from the previous day's couch position, 2) DICOM
      origin or isocenter is different between two plans (imaging or treatment), and 3)
      Patient shift in opposite direction than intended. The main effect of these
      failures was to cause an override of couch parameters. Based on these results, we
      modified our processes, introduced new QA and software checks and developed new
      tolerance tables so as to improve system robustness and increase our success rate
      at catching failures before they can affect the patient. It has been a year since
      we made these modifications. Based on our results, we have reduced the number of
      overrides at our center from a maximum of 20.5% to a maximum of 6.3%, with an
      average at 4% of daily treatments. Our results suggest that FMEA is an effective
      tool in improving treatment quality that could be used in other centers.

PMID- 28516697
TI  - Poster - Thur Eve - 49: Application of plastic scintillating detectors to
      orthovoltage x-ray measurements.
AB  - Plastic scintillating detectors (PSDs) have found numerous dosimetric
      applications in radiotherapy due to their approximate water equivalence at high
      energies and their small physical size. At low photon energies, however, the
      ratio of mass attenuation coefficients (PSD : water) deviates from unity, which
      potentially limits their utility in this range. In this work, measurements of
      orthovoltage cutout factors were made with PSDs and and ion chamber. Results were
      compared to Monte Carlo simulations of the same geometry. Results indicated that
      the PSDs performed better than the IC in almost all field sizes. Further work is
      required to more thoroughly characterize the Monte Carlo model of the x-ray unit
      and to investigate any discrepancies that might have resulted from slight
      differences in the effective point of measurement of the two detector systems.

PMID- 28516698
TI  - Poster - Thur Eve - 20: Serial FDG 4DPET imaging during radiotherapy in advanced
      lung cancer patients.
AB  - The availability of respiratory synchronized PET (4DPET) imaging has enabled more
      accurate analysis of metabolic response since motion blur is minimized. We
      present our preliminary analysis of serial FDG 4DPET images acquired at weeks 0,
      2, 4, and 7 during radiotherapy of seven stage II-III NSCLC patients. The tumor
      and nodal PTV of the week 0 images restrained a 4DPET image thresholding
      algorithm to automatically contour SUV levels ranging from 20 to 80% of the
      maximum SUV, creating an intensity volume histogram (IVH) for each week. These
      contours allowed analysis of PET volumes and standard PET metrics such as SUVmax
      and SUVmean . We found a trend for decreasing SUVmax and SUVmean over a treatment
      course in both the tumor and nodal regions. On average, the SUVmax within the
      tumor decreased by 17+/-13% (1 SD) after 2 weeks, 30+/-13% after 4 weeks, and
      39+/-19% after 7 weeks of radiotherapy. Decreasing volume trends were also
      observed in the 20 to 80% max SUV autocontours, ranging from 26+/-29% to 50+/-40%
      respectively, over 7 weeks of treatment. Only one patient demonstrated an
      increase in FDG uptake within the tumor volume between week 0 and week 2 of
      treatment, and was also the only patient to recur locally at 3 months following
      treatment. Changes in tumor metabolism over the course of advanced NSCLC
      radiotherapy are quantifiable with serial FDG 4DPET imaging. Preliminary analysis
      suggests that variations in these trends could be useful in identifying non
      responding patients that may require an alternative radiotherapeutic approach.

PMID- 28516699
TI  - Poster - Thur Eve - 60: Physical and dynamic wedges in radiotherapy for rectal
      cancer: A dosimetric comparison.
AB  - The aim of this study is to compare the dosimetry of the physical wedge (PW) and
      enhanced dynamic wedge (EDW) in radiotherapy of rectal cancer. Two wedge angles
      of 45 degrees  and 60 degrees  were used in the comparison due to the size of the
      pelvis contour. 6 and 15 MV photon beams produced from a Varian 21 CD linear
      accelerator were used. Thirty rectum patients were investigated using the three
      field technique. Treatment plans using the PWs and EDWs were created using the
      Eclipse treatment planning system. Monitor units, plan normalization value,
      maximum and minimum doses in the planning target volume (PTV), dose conformity
      index, dose homogeneity index and uniformity index were determined for each
      treatment plan. The average dose coverage for the PTV with EDW and PW plans were
      compared. The PTV received prescription doses of 100.9+/-0.74%, 101.01+/-1.63%
      for the EDW (45 degrees , 60 degrees ) compared to 101.2+/-1.65%, 101.3+/-1.33%
      for the PW (45 degrees , 60 degrees ). Homogeneity indices were (0.11+/-0.02%,
      0.11+/-0.05%) for the EDW (45 degrees , 60 degrees ), and (0.15+/-0.1%, 0.16+/
      0.11%) for the PW (45 degrees , 60 degrees ), respectively. The EDW at 45 degrees
      had better target coverage with higher conformity index value of 0.98 +/- 0.01
      compared to the other wedges. A statistically significant (p < 0.01) change in
      plan normalization values and fewer monitor units were found using the EDW at 45
      degrees . We conclude that the EDW at 45 degrees  results in an improvement to
      the plan evaluation parameters presented and thus increases dose efficacy for
      radiotherapy of rectal cancer.

PMID- 28516700
TI  - Poster - Thur Eve - 31: RapidArc total body photon irradiation: A feasibility
      study.
AB  - Total body photon irradiation (TBI) may be delivered with a number of standard
      techniques, typically using extended SSD geometries to obtain large field sizes.
      Since 1982 we have treated over 620 patients (adult and pediatric) mostly in the
      floor-located prone/supine treatment position with AP/PA beams using a column
      mounted 4 MV linac, and more recently with a fixed field, extended SSD, Cobalt
      teletherapy unit. This treatment position has many advantages for TBI including
      ease of delivery (especially for pediatric or compromised patients), improved
      dose uniformity, simplicity for partial or complete organ shielding, and imaging
      capabilities to name a few. In an effort to transfer this technique to a
      conventional isocentric linac, we have undertaken a feasibility study for
      RapidArc based extended SSD total body irradiation. Proof of principle was first
      explored using the DBD (Dynamic Beam Delivery) toolbox to configure a 6 MV beam
      with an 80 degree arc, centered on the 12 o'clock gantry angle with a sliding
      window beam. This was followed by the development of an ECLIPSE generated 80
      degree RapidArc plan. Initial measurements were conducted with a Varian 21EX
      using the 6 MV DBD beam to explore characteristics such as PDD, surface dose, off
      axis ratios, output, dose per MU, and linearity. Subsequently ECLIPSE generated
      RapidArc TBI plans using similar partial arcs were also evaluated. Encouraged by
      our results, we believe this technique shows potential for making floor-located
      AP/PA total body photon irradiation possible for any standard RapidArc enabled
      isocentric linac.

PMID- 28516701
TI  - Poster - Thur Eve - 22: Bone heterogeneity in kV x-ray radiotherapy.
AB  - This study evaluated the dosimetric impact of bone heterogeneity on the surface
      dose and dose prescription, when dose is assumed to be prescribed on a
      homogeneous medium in kV x-ray radiotherapy. A heterogeneous phantom containing a
      thin water layer (thickness = 1-5 mm) over a bone (thickness =1 cm) was used to
      mimic treatment sites of forehead, knee and chest wall. The phantom was
      irradiated by a 220 kVp photon beam with field size of 5 cm diameter. Percentage
      depth dose, surface dose and photon energy spectrum with different thicknesses of
      water were determined using Monte Carlo simulations (the EGSnrc code) with
      experimental verifications using parallel-plate ionization chamber and
      radiochormatic film. Our results (treatment cone of 5 cm diameter) showed that
      the surface dose increased in a range of 2.5-3.7% when the water layer above the
      bone was increased from 1 to 5 mm. However, the surface dose did not increase
      linearly with the increase of water thickness, and the maximum increase of
      surface dose was found at a water thickness of 3 mm. Results of the percentage
      depth dose showed that the maximum bone dose was about 210% higher than the
      surface dose in the heterogeneous phantom. It is concluded that in treatment
      sites having a thin layer of tissue over a bone in kV x-ray radiotherapy, if
      increased surface dose due to bone heterogeneity is not considered, this will
      result in an additional dosimetric uncertainty narrowing down the total error
      margin (5%).

PMID- 28516702
TI  - Poster - Thur Eve - 62: Assessing the clinical application of the van Herk margin
      formula for lung radiotherapy.
AB  - According to a margin recipe developed by van Herk et al. the Planning Target
      Volume (PTV) margin to ensure the Clinical Target Volume is covered by at least
      95% of the prescribed dose can be calculated by applying the following formula: M
      = 2.5Sigma + 1.64sigma2 - 1.64sigmap. In the van Herk Margin formula (VHMF),
      Sigma is the standard deviation (SD) of all systematic errors; sigma is the SD of
      random errors and sigmap is the width of the penumbra. This formula is based on
      an idealized dose profile model that may not account for factors that vary
      significantly in lung radiotherapy such as tumour size and tissue density. The
      purpose of this study was to use accurate dose calculation algorithms and
      respiratory motion modeling to investigate the validity of the VHMF for lung
      radiotherapy. Random and systematic errors were simulated in treatment planning
      software using dose accumulation techniques for clinically relevant 3DCRT and
      IMRT treatment plans constructed on virtual phantoms. Phantom parameters such as
      target size, peak-to-peak motion amplitude and tissue density were varied to
      investigate their impact on the systematic and random error components of the
      margin formula. The VHMF was found to provide adequate dose coverage for all
      plans generated on different target sizes and motion amplitudes. Although
      discrepancies existed between idealized and realistic dose profiles in water and
      lung, the dose coverage defined by the V95 was not affected. The margin formula
      was found to be robust; however, further investigation of the influence of plan
      conformity is needed.

PMID- 28516703
TI  - Poster - Thur Eve - 33: A comprehensive analysis of the effect of respiratory
      motion on the delivery of IMRT to advanced stage non-small cell lung cancer.
AB  - The goal of this work was to quantify the interplay effect of various IMRT
      delivery techniques in the treatment of Stage III non-small cell lung cancer.
      Five patients with significant tumour motion were retrospectively planned on the
      average 4D-CT dataset with eight different IMRT techniques: three Tomotherapy
      techniques with different beam-widths, two step-and-shoot (SS-IMRT) with
      different complexity, one sliding-window (SW-IMRT), and two VMAT techniques
      (RapidArc and SmartArc). Each plan was calculated on a delivery verification
      phantom that was mounted on a programmable respiratory motion platform and
      delivered under the following motion conditions: 1) Static; 2) sinusoidal with 4
      different amplitudes; 3) Real Patient Breathing. A standard 3%/3mm gamma analysis
      compared the sum of all 30 fractions to their corresponding 60Gy/30fx plan. One
      way ANOVA was conducted for respiratory motion amplitude and IMRT modality,
      separately. There were no significant differences amongst the modalities at any
      amplitude level. However, for individual modalities, there were significant
      differences amongst different amplitudes except for Tomo-2.5cm (p=0.260). Post
      hoc Tukey tests determined that detectable significant differences amongst any
      motion level, including real-patient breathing, were observed when compared to
      the 20mm amplitude for all modalities except Tomo-2.5cm and SmartArc. SW-IMRT
      showed significant differences at 15mm when compared to both static (p=0.033) and
      5mm (p=0.008). All methods except for RapidArc averaged out to clinically
      acceptable gamma pass rates up to 15mm. In conclusion, for motion levels above
      15mm, the interplay effect can be clinically unacceptable. However, the interplay
      effect at these motion levels does not appear to be modality dependent.

PMID- 28516704
TI  - Poster - Thur Eve - 44: Digital tomosynthesis image quality in a Co-60 treatment
      beam.
AB  - Image guidance capability is an important feature of modern radiotherapy
      machines. Cobalt-60 units will require some form of image guidance if they are to
      be brought up to modern standards. Imaging in the treatment beam is an appealing
      option, for reasons of simplicity and cost, but the dose needed to produce cone
      beam CT images in a Co-60 treatment beam is too high for this modality to be
      clinically useful. Digital tomosynthesis (DT) offers a quasi-3D image, of
      sufficient quality to identify bony anatomy or fiducial markers, while delivering
      a much lower dose than CBCT. A series of experiments were conducted on a
      prototype Co-60 cone beam imaging system to quantify the resolution, selectivity,
      geometric accuracy and contrast sensitivity of Co-60 DT. Although the resolution
      was severely limited by the penumbra cast by the ~2cm diameter source, it was
      possible to identify high contrast objects on the order of 1 mm in width, and
      bony anatomy in anthropomorphic phantoms was clearly recognizable. Low contrast
      sensitivity down to electron density differences of 3% was obtained, for uniform
      features of similar thickness. The conventional shift-and-add algorithm was
      compared to the FDK filtered backprojection algorithm using several different
      spatial filters. The Co-60 DT images were obtained with a total dose of 5 to 15
      cGy. We conclude that, should Co-60 radiotherapy units be upgraded with image
      guidance capabilities, filtered backprojection DT in the treatment beam is a
      versatile and promising modality that would be well suited to the task of patient
      positioning.

PMID- 28516706
TI  - Poster - Thur Eve - 26: Interfraction reproducibility of heart position during
      breast irradiation using Active Breathing Control.
AB  - The moderate deep-inspiration breath hold (mDIBH) technique using the Active
      Breathing Coordinator (ABC) from Elekta is used in our clinic to lower the heart
      dose during left breast irradiations. The purpose of this work was to investigate
      the interfraction reproducibility of the heart to chest distance during these
      treatments and to evaluate the dosimetric effect of any changes in the heart
      position. Daily CBCT images were available for 5 patients who had been treated
      with ABC tangents and a cavity boost. On these images, one-dimensional
      measurements of the distance between the heart and the chest wall were taken at
      two anatomical locations corresponding roughly with the location where the
      radiation field most likely intercepts the heart. The average change in this
      distance was interpreted as a shift of the heart position. To assess the effect
      of this shift on the delivered heart dose, the heart contours in the clinical
      plans of the corresponding patients were shifted towards the treatment field
      using standard Pinnacle tools. Although the ABC device allows good
      reproducibility of the volume of air held, this does not warrant reproducibility
      of heart position for all patients during treatment. The largest average heart
      shift extracted from CBCT images in this study was 6.2mm. The heart dose
      reconstructed using this shift for the corresponding patient also showed the
      largest effect. However, even in the presence of a systematic heart shift of this
      magnitude, the ABC plan still showed superior heart dose reduction compared to
      the free-breathing plan.

PMID- 28516705
TI  - Poster - Thur Eve - 55: Monte Carlo simulations of variations in planned dose
      distributions in a prostate patient population.
AB  - Clinical outcome studies with clear and objective endpoints are necessary to make
      informed radiotherapy treatment decisions. Commonly, clinical outcomes are
      established after lengthy and costly clinical trials are performed and the data
      are analyzed and published. One the challenges with obtaining meaningful data
      from clinical trials is that by the time the information gets to the medical
      profession the results may be less clinically relevant than when the trial began,
      An alternative approach is to estimate clinical outcomes through patient
      population modeling. We are developing a mathematical tool that uses Monte Carlo
      techniques to simulate variations in planned and delivered dose distributions of
      prostate patients receiving radiotherapy. Ultimately, our simulation will
      calculate a distribution of Tumor Control Probabilities (TCPs) for a population
      of patients treated under a given protocol. Such distributions can serve as a
      metric for comparing different treatment modalities, planning and setup
      approaches, and machine parameter settings or tolerances with respect to outcomes
      on broad patient populations. It may also help researchers understand differences
      one might expect to find before actually doing the clinical trial. As a first
      step and for the focus of this abstract we wanted to see if we could answer the
      question: "Can a population of dose distributions of prostate patients be
      accurately modeled by a set of randomly generated Gaussian functions?" Our
      results have demonstrated that using a set of randomly generated Gaussian
      functions can simulate a distribution of prostate patients.

PMID- 28516708
TI  - Poster - Thur Eve - 48: An inexpensive and convenient phantom for quality
      assurance in image guidance based radiosurgery.
AB  - This work describes the design and use of an inexpensive phantom designed for
      precision measurements in radiosurgery quality assurance. The main features of
      this simple phantom include its solid water construction, interchangeable ion
      chamber holders and film registration system, thus allowing for measurement of
      small fields with several detectors using the same phantom. The entire phantom
      was constructed using one 30cm * 30cm * 3cm slab of solid water. The phantom
      contains a slot that allows for the placement of two small volume ion chambers
      (liquid and A1SL) via custom inserts near the center of the phantom. In addition,
      the plug can be filled for film measurements. The phantom can be split down the
      center to allow for the placement of a film. As opposed to registering film to
      room based markers, such as lasers, the phantom contains radio-opaque fiducials
      that puncture the film while also providing a method to register the film images
      to exported dose planes. In addition to the markers used for film registration,
      the phantom contains several external beebees that can be used to avoid ambiguity
      in image registration when using image guidance for setup. This simple phantom
      contains many features of other much more expensive phantoms designed for this
      purpose and has been found to be very useful clinically and in departmental
      research. The key elements of this phantom could be included in several other
      designs allowing it to be reproduced in other centers.

PMID- 28516707
TI  - Poster - Thur Eve - 37: Improved clustering MLC leaf-sequencing algorithm for
      step-and-shoot IMRT.
AB  - This study examines how to reduce the complexity of fluence map generated using
      an improved clustering leaf-sequencing method, and evaluates such method in step
      and-shoot intensity-modulated radiotherapy (IMRT). Based on the current equal
      space grouping algorithm for multileaf collimator (MLC) leaf sequence, we
      proposed an improved K-means grouping algorithm which can replace the
      stratification routine in the program of existing leaf sequence. The improved
      algorithm can be thought of as a gradient descent procedure, which begins at
      starting cluster centroids, and iteratively updates these centroids to decrease
      the objective function. The K-means always converge to a local minimum depending
      on the starting cluster centroids. The K-means algorithm continuously updates
      cluster centroids until the local minimum is reached. We compare the leaf
      sequencing results in term of numerical values from the improved K-means and
      equal-space grouping algorithm. A representative 1D intensity map from a clinical
      treatment plan was investigated and optimized by the K-means and equal-space
      grouping algorithm. It was found that the K-means algorithm decreased the dose
      square error from 53.67 to 35.27. Moreover, the normalized square differences of
      the equal-space and K-means algorithm are equal to 2881 and 1244, respectively.
      The results demonstrated an improvement in accuracy achievable by allowing the
      fluence map to be defined in an optimal way rather than using the pre-defined
      criteria. Therefore, the K-means leaf-sequencing algorithm can better simulate
      the distributions of the input fluence data compared to the traditional grouping
      algorithm in step-and-shoot IMRT.

PMID- 28516709
TI  - Poster - Thur Eve - 19: Risk assessment of clinical radiation processes using
      failure modes and effect analysis.
AB  - The aim of this work was to apply failure modes and effect analysis (FMEA) to
      assess risk in two radiation planning and treatment processes; our on-call (out
      of-clinical hours) process and our tomotherapy process. The motivation was
      provided by analysis of 2506 adverse incidents reported over a 5 year period, the
      on-call process for giving rise to a higher than expected number of incidents and
      our tomotherapy process for the reverse. For the on-call scenario, three separate
      processes were analysed: our current process, our current process incorporating a
      software upgrade eliminating several planning steps and a fully integrated
      process in which the patient is imaged, planned and treated on a single platform
      (TomoTherapy Hi Art, Accuray Incorporated, Sunnyvale, CA). After construction of
      a detailed process map for each case, a multidisciplinary group identified
      potential failure modes for each process step, the effects of each failure and
      existing controls. Risk probability numbers were determined from severity,
      frequency of occurrence and detectability scores assigned to each failure mode
      according to a standard scale. The results were analysed to identify and
      prioritise feasible and effective process improvements. For the on-call process,
      our current workflow was identified as incurring the highest risk of the three
      processes analysed, demonstrating quantitatively the value of the software
      upgrade and providing a clear rationale for the associated expense. In summary,
      we have found FMEA to be a feasible tool for assessing relative risk in a
      clinical process. However, operational and resource issues must be considered
      separately.

PMID- 28516711
TI  - Poster - Thur Eve - 30: Comparison of treatment planning and delivery performance
      of VMAT versus IMRT.
AB  - The purpose of this study was to determine whether VMAT (Varian RapidArc TM)
      treatment planning and delivery performance is in compliance with accepted
      quality assurance tolerances developed for sliding window IMRT. We present an
      analysis of data for over 1300 patients treated with VMAT and IMRT over a period
      of three years. Data was acquired on 6 dosimetrically matched linacs for sites
      including head and neck, brain, gynaecological, and a variety of other cancer
      cases treated with 6 MV. We have demonstrated that it is possible to
      dosimetrically match multiple Varian iX linacs with the millennium series MLC
      using a sliding gap and intercept test. QA is performed by Monte Carlo simulation
      and ion chamber measurement comparisons with Varian Eclipse TPS as well as linac
      log file analysis of MLC positions, gantry angles and monitor units on each
      patient. Point dose and 3D gamma analysis indicate that agreement between Eclipse
      and measurement or Monte Carlo calculation is site specific, with the dosimetric
      leaf gap parameter in Eclipse optimized for the most frequently treated site
      Point dose agreement within 2% and gamma pass rate of > 95% (3%/ 3 mm) is
      achievable for all sites for both IMRT and VMAT. Linac log file analysis
      indicates that planned MLC positions are achieved within 2 mm >99.7% of the time
      for both sliding window IMRT and VMAT. Planned gantry angles are achieved within
      0.6 mm 99.8% of the time and planned MU's within 0.1 mm are achieved 99.8% of the
      time for VMAT.

PMID- 28516710
TI  - Poster - Thur Eve - 59: Dosimetric evaluation on the variation of PTV coverage
      due to patient size reduction using the prostate dose-volume factor in prostate
      radiotherapy.
AB  - We proposed to use the prostate dose-volume factor (PDVF), derived from the dose
      volume dataset of planning target volume (PTV) in prostate radiotherapy to
      evaluate treatment plans of prostate volumetric modulated arc therapy (VMAT) and
      intensity modulated radiotherapy (IMRT). To demonstrate plan evaluation using
      PDVF, VMAT and 7-beam IMRT plans were created in three patients with prostate
      volumes equal to 32, 48.4 and 86.5 cm3 . Dose variation of PTV was made by
      reducing the body contour of the patients with reduced depth equal to 0.5 - 2 cm,
      mimicking a patient size reduction in the treatment. The Gaussian error function
      was used to model the cumulative dose-volume histogram of the PTV, and PDVF was
      calculated as per the parameters of the error function. PDVF = 1 reflects an
      ideal PTV coverage (i.e. 100% prescribed dose in 100% target volume). We found
      that for PDVF ranged 0.98 - 1 in prostate VMAT and IMRT without patient size
      change, reduced depth led to PDVF decreasing 0.03 +/- 4.7 * 10-4 (VMAT) and 0.04
      +/- 9.7 * 10-3 (IMRT) per cm for the patients. The variation of PTV coverage on
      the prostate volume due to the reduced depth was less significant in VMAT plans
      than IMRT. It is concluded that PDVF was successfully used to evaluate the
      variation of PTV coverage due to the weight loss of patient in prostate VMAT and
      IMRT. Degradation of PTV coverage in prostate VMAT regarding patient size
      reduction is less significant than that in IMRT.

PMID- 28516712
TI  - Poster - Thur Eve - 41: Effect of beam symmetry on enhanced dynamic wedge quality
      assurance and tolerance levels.
AB  - Wedged fields are common in three dimensional conformal radiation therapy and
      require appropriate quality assurance (QA). Currently, our centre calculates the
      angle of enhanced dynamic wedge (EDW) deliveries with the PROFILER at a monthly
      frequency but Canadian guidelines on the recommended QA of enhanced dynamic
      wedges are not available yet. TG-142 recommendations include monthly validation
      of the central axis wedge factors with only annual verification of wedge
      profiles. Our monthly QA results have demonstrated a sensitivity of the
      calculated EDW angle to open beam symmetry. The goal of this work is to compare
      wedge angle and direct profile comparison as QA measures of EDW delivery and
      determine appropriate parameter tolerances. The impact of open field symmetry
      variations on EDW profiles was determined by varying beam symmetry with a test
      potentiometer and measuring the resulting EDW beam profile with the PROFILER. A
      calculated wedge angle and direct profile comparison were used to describe the
      deviations in EDW deliveries. The impact of the deviations on typical plans
      incorporating wedged fields was evaluated by constructing 'equivalent wedges' to
      the profile deviations using mixed 60 degree and open field beams and performing
      plan comparisons in Eclipse. Beam symmetry was observed to have a significant
      impact on wedge angle for small angle wedges, with a 1% symmetry tolerance
      allowing a 3.4 degree range of wedge angles for a nominal 10 degree wedge. Direct
      profile comparison allows a more consistent definition of a dose based tolerance
      range to be applied without angle dependent tolerances.

PMID- 28516713
TI  - Poster - Thur Eve - 32: Water tank referenced calibration method for detector
      array devices.
AB  - INTRODUCTION: Detector array devices, such as the I'mRT Matrixx (IBA Dosimetry),
      provide a means of evaluating beam profiles with respect to gantry for a range of
      dose rates and monitor units. The relative calibration of these devices is
      typically highly susceptible to even relatively small variations in beam output.
      An alternative method is proposed here, which directly references the device
      detector response to water tank data. METHODS: The Matrixx response was measured
      at the four cardinal angles for three devices. A calibration factor was
      determined for each orientation of the Matrixx device by dividing a water tank
      measured profile by the Matrixx response for the in-plane and cross-plane
      detectors. A geometric mean of each orientation was used as the estimate of the
      calibration coefficient. RESULTS: Before calibration, the three-detector average
      of the deviation from the profile measured in the water tank centered on each of
      the horns was 0.4% (SD 0.2%); applying the calibration procedure reduced this to
      0.1% (SD 0.1%). The energy independence of the proposed relative calibration was
      also confirmed. A comparison of the linac output for relatively short Matrixx
      acquisitions to the longer water tank acquisition suggested some difference. This
      difference was mitigated by averaging. CONCLUSIONS: The proposed water tank
      reference calibration procedure is an effective means of determining the relative
      calibration of a detector array and mitigates the effect of compound error by
      avoiding the recursive algorithm of typical calibration methods. In addition it
      has the benefit of being directly relatable to commissioning beam data.

PMID- 28516714
TI  - Poster - Thur Eve - 43: Is faster always better? An evaluation of frame rate
      effects on continuous acquisition mode EPID imaging for dose verification.
AB  - INTRODUCTION: As radiotherapy moves towards intensity modulated arc therapy (arc
      IMRT), there is a need for electronic portal imaging (EPID) to move towards
      continuous acquisition (cine) mode for dosimetric verification purposes. However,
      as the EPID resolution and frame rate (fps) increase, so does the computational
      burden of image processing. We investigated the reliability of cine mode EPID
      imaging in IMRT as a function of frame rate. METHODS: We acquired EPID images
      continuously while running an IMRT plan (6MV photons, 150MU, dose rate =
      300MU/min) with frame rates ranging from 1-12 fps, as well as a single integrated
      mode image. Each cine dataset was then averaged to form a single image, which was
      compared with the integrated mode image by means of a pixel-by-pixel absolute
      value subtraction. RESULTS: Although a greater frame rate gave better agreement
      with the integrated mode image in all cases, the relative benefit diminished with
      increasing frame rate. In particular, for the IMRT plan delivered, there was
      little benefit of imaging faster than 6 fps, and virtually no benefit in
      increasing from 9 to 12 fps. In contrast, 12 fps produces twice the number of
      images as 6 fps which significantly increases the image processing and data
      storage burdens. CONCLUSION: Increasing frame rate in cine mode EPID imaging may
      be beneficial in some cases, but there is likely a threshold level above which no
      relevant additional information is obtained. Further research to determine the
      ideal frame rate for any particular IMRT or arc-IMRT plan is warranted.

PMID- 28516715
TI  - Poster - Thur Eve - 54: A software solution for ongoing DVH quality assurance in
      radiation therapy.
AB  - PURPOSE: A program has been developed in MATLAB for use in quality assurance of
      treatment planning of radiation therapy. It analyzes patient DVH files and
      compiles dose volume data for review, trending, comparison and analysis. MATERIAL
      AND METHODS: Patient DVH files are exported from the Eclipse treatment planning
      system and saved according to treatment sites and date. Currently analysis is
      available for 4 treatment sites; Prostate, Prostate Bed, Lung, and Upper GI, with
      two functions for data report and analysis: patient-specific and organ-specific.
      The patient-specific function loads one patient DVH file and reports the user
      specified dose volume data of organs and targets. These data can be compiled to
      an external file for a third party analysis. The organ-specific function extracts
      a requested dose volume of an organ from the DVH files of a patient group and
      reports the statistics over this population. A graphical user interface is
      utilized to select clinical sites, function and structures, and input user's
      requests. RESULTS: We have implemented this program in planning quality assurance
      at our center. The program has tracked the dosimetric improvement in GU sites
      after VMAT was implemented clinically. It has generated dose volume statistics
      for different groups of patients associated with technique or time range.
      CONCLUSION: This program allows reporting and statistical analysis of DVH files.
      It is an efficient tool for the planning quality control in radiation therapy.

PMID- 28516717
TI  - Poster - Thur Eve - 65: Optimization of an automatic image contouring system for
      radiation therapy.
AB  - Intensity modulated radiation therapy (IMRT) is an advanced technique used to
      concentrate the prescribed dose in the tumour while minimizing exposure to
      healthy tissues. Success in IMRT is greatly dependent upon the localization of
      the target volume and normal tissue, thus accurate contouring is crucial. In this
      paper, we describe an automated atlas-based image contouring system and our
      approach for improving the system by performing a full-scale optimization of
      registration parameters using high-performance computing. To achieve this, we use
      manually pre-contoured CT images of ten head and neck patients. For any parameter
      set, each patient data is registered with the remaining patients. Accuracy of the
      resulting contours is determined automatically by comparing their overlap with
      manually defined targets using Dice's similarity coefficient (DSC). This allows
      us to compare all permutations of the image registration parameter sets and input
      data to investigate their impact on final contour accuracy. Investigating the
      parameter space required 27,000 image registrations and 216,000 DSC computations.
      To perform these registrations we introduced a large cluster of high-performance
      computers and developed a parallel testing harness. The metrics collected from
      the tests show a wide range of performance, indicating that parameter selection
      is crucial in our contouring system. By selecting an optimized parameter set, we
      increased the mean overlap of the automatically contoured regions of interest by
      50% and reduced registration time by 50% compared to the original parameters. Our
      findings illustrate that full-scale optimization is an effective method for
      improving the performance of the automated image contouring system.

PMID- 28516716
TI  - Poster - Thur Eve - 25: In vivo dosimetric verification of intensity-modulated
      radiation therapy.
AB  - Dosimetric verification of patient treatment plans has become increasingly
      important due to the widespread use of complicated delivery techniques. IMRT and
      VMAT treatments are typically verified prior to start of the patient's course of
      treatment, using a point dose and/or a film measurement. Pre-treatment
      verification will not detect patient or machine-related errors; therefore, in
      vivo dosimetric verification is the only way to determine if the patient's
      treatment was delivered correctly. Portal images were acquired throughout the
      course of five prostate and six head-and-neck patient IMRT treatments. The
      corresponding predicted images were calculated using a previously developed
      portal dose image prediction algorithm, which combines a versatile fluence model
      with a patient scatter and EPID dose prediction model. The prostate patient image
      agreement was found to vary day-to-day due to rectal gas pockets and the effect
      of adjustable support rails on the patient couch. The head-and-neck patient
      images were observed to be more consistent daily, but an increased measured dose
      was evident at the periphery of the patient, likely due to patient weight loss.
      The majority of the fields agreed within 3% and 3 mm for greater than 90% of the
      pixels, as established by the chi-comparison. This work demonstrates the changes
      in patient anatomy that are detectable with the portal dose image prediction
      model. Prior to clinical implementation, the effect of the couch must be
      incorporated into the model, the image acquisition must be automatically
      scheduled and routine EPID QA must be undertaken to ensure the collection of high
      quality EPID images.

PMID- 28516718
TI  - Poster - Thur Eve - 36: Out-of-Field dose in craniospinal irradiation.
AB  - The risk of radiotherapy induced secondary cancer depends on the integral dose
      delivered to the patient where the dose delivered within the radiation field is
      accounted for, as well as dose to out-of-field organs from scattered and leakage
      radiation. While commercial treatment planning systems allow accurate
      determination of in-field dose, they are generally not capable of accurate out-of
      field dose prediction. Secondary cancer risk is especially an issue in
      craniospinal treatments where involved patients are often children or young
      adults. In this work we therefore propose a mathematical model that accurately
      predicts out-of-field dose for patients treated by craniospinal irradiation at
      the American University of Beirut Medical Center. An anthropomorphic phantom was
      imaged, planned and treated, with thermoluminescent dosimeters inserted in the
      phantom at in-field and out-of-field locations. The measurements showed that our
      treatment planning system calculated accurately (within 2%) dose inside the
      field, but did not perform well at points just outside the field edge and
      consistently underestimated the dose at points further away from the field edge.
      From the out-of-field measured data, a model was developed that predicts out-of
      field dose at a point in the patient based on the distance of that point to the
      treatment field edge. The developed model is of the double-gaussian type; it
      contains parameters that can be tuned to make it applicable in other centers
      where linac geometry and treatment techniques may differ.

PMID- 28516719
TI  - Poster - Thur Eve - 47: Evaluation of the ArcCHECK device for commissioning and
      patient-specific QA.
AB  - The most promising method of accurately verifying VMAT treatments is by direct
      dose measurement over the three dimensions of irradiated volume. ArcCHECK device
      (Sun Nuclear, Melbourne, FL) have the potential to detect delivery errors on the
      treatment machine due to mechanical problems resulting from gantry and MLC
      motion. The estimation of the dosimetric leaf gap (DLG) parameter for Varian MLC
      (Varian Medical Systems, Palo Alto, CA) was attempted using ArcCHECK. Finding the
      optimal DLG value for use in TPS requires a measuring device like ArcCHECK to be
      employed especially in highly intensity modulated fields. In addition, ArcCHECK
      was used to assess the effect of positional error of MLC leaf in a given VMAT
      plan. Patient-specific QA tests were performed using the ArcCHECK device. QA
      results of patient plans that failed considering portal dosimetry technique were
      reassessed with ArcCHECK measurements for IMRT plans. The preliminary test
      results and performance of the ArcCHECK device were very encouraging. VMAT plans
      for head and neck cases were generated and their delivery was evaluated using
      ArcCHECK. Results have shown a success rate greater than 90% in the quality
      assurance of individual plans. Optimal DLG value was detected using ArcCHECK.
      Also, the device showed enough sensitivity to identify failed QA plans. Moreover,
      MLC central leaf pair position offset in a VMAT plan of the order of 1mm was
      fairly distinguished by ArcCHECK measurements.

PMID- 28516720
TI  - Poster - Thur Eve - 18: Characterization of a camera and LED lightbox imaging
      system for radiochromic film dosimetry.
AB  - Radiation therapy treatment modalities continue to develop and have become
      increasingly complex. With this, dose verification and quality assurance (QA) is
      of great importance to ensure that a prescribed dose is accurately and precisely
      delivered to a patient. Radiochromic film dosimetry has been adopted as a
      convenient option for QA, because it is relatively energy independent, is near
      tissue equivalent, and has high spatial resolution. Unfortunately, it is not
      always easy to use. In this study, preliminary work towards developing a novel
      method of imaging radiochromic film is presented. The setup consists of a camera
      mounted vertically above a lightbox containing red LEDs, interfaced with computer
      image acquisition software. Imaging results from this system will be compared
      with imaging performed using an Epson Expression 10000XL scanner (a device in
      common clinical use). The lightbox imaging technique with camera readout is much
      faster relative to a flatbed scanner. The film measurements made using the camera
      are independent of film orientation, and show reduced artifacts, so that there
      are fewer corrections required compared to the use of flatbed scanners. Optical
      scatter also appears to be less of an issue with this design than with the flat
      bed scanner. While further work needs to be done to optimize the lightbox imaging
      system, the lightbox system shows great promise for a rapid, simple, and
      orientation independent setup, improving on existing film scanning systems.

PMID- 28516721
TI  - Poster - Thur Eve - 58: The clinical significance of couch top modeling in VMAT
      and IMRT treatment planning.
AB  - In recent years, carbon fibre couch tops have become popular in radiation therapy
      with marketed attributes such as high tensile strength, light weight, and
      relative radiotranslucence. We have performed a detailed analysis of the iBEAM
      evo couch top using two models created in the Pinnacle v9.0 treatment planning
      system. The first model is a single ROI, and its thickness and shape was
      determined based on attenuation factor measurements in cylindrical phantoms. The
      second model is a thin shell made of two ROIs with exact outer dimensions as the
      real couch top. The couch top attenuation was found to range from 2% to 6.5% for
      a 6 MV beam energy. The two models were found to match the attenuation factor
      measurements to within 4.2% and 1.7%, respectively. The clinical impact of the
      couch top models was examined in 4 VMAT and 4 IMRT prostate plans by comparing
      mean and maximum point doses, DVHs, and measurements (VMAT plans only) using
      Gamma analysis. A very small, but clinically insignificant difference was
      observed between the two couch top models for both VMAT and IMRT plans. The lack
      of a couch top model in treatment planning was also examined and found to result
      in ~ 1% average underdose to the PTV. This study suggests that the iBEAM evo
      couch top is relatively radiotranslucent for typical VMAT and IMRT delivery as
      long as the number of control points with extremely oblique beam angles is
      relatively small.

PMID- 28516722
TI  - Poster - Thur Eve - 29: Detecting changes in IMRT QA using statistical process
      control.
AB  - Statistical process control (SPC) methods were used to analyze 239 measurement
      based individual IMRT QA events. The selected IMRT QA events were all head and
      neck (H&N) cases with 70Gy in 35 fractions, and all prostate cases with 76Gy in
      38 fractions planned between March 2009 and 2012. The results were used to
      determine if the tolerance limits currently being used for IMRT QA were able to
      indicate if the process was under control. The SPC calculations were repeated for
      IMRT QA of the same type of cases that were planned after the treatment planning
      system was upgraded from Eclipse version 8.1.18 to version 10.0.39. The initial
      tolerance limits were found to be acceptable for two of the three metrics tested
      prior to the upgrade. After the upgrade to the treatment planning system the SPC
      analysis found that the a priori limits were no longer capable of indicating
      control for 2 of the 3 metrics analyzed. The changes in the IMRT QA results were
      clearly identified using SPC, indicating that it is a useful tool for finding
      changes in the IMRT QA process. Routine application of SPC to IMRT QA results
      would help to distinguish unintentional trends and changes from the random
      variation in the IMRT QA results for individual plans.

PMID- 28516723
TI  - Poster - Thur Eve - 40: Dynamic arc sliding window tests for checking MLC gap
      consistency in rapid arc delivery.
AB  - MLC gap control is critical for dosimetric accuracy in rotational IMRT (RapidArc,
      VMAT) treatments. Systematic MLC gap change of 1 mm may cause 3-4% change of EUD
      to PTV for a typical H&N RapidArc plan. Therefore it is important to monitor MLC
      gap through QC procedures. For this purpose, we have created dynamic arc sliding
      window (SW) plans with fixed width MLC slits sliding across a jaw defined field.
      Plans with MLC slit widths of 5, 10, 15, and 20 mm, respectively, and the same
      length of 20 cm (in Y direction) were created with 6MV photons in a single arc of
      gantry angles from 182 degrees  to 178 degrees . Dose delivered from these SW
      plans was measured using an ion chamber in a cylindrical phantom placed at
      isocentre, and values for dosimetric leaf gap (DLG) were derived based on
      relative dose measurements. DLG measured in dynamic arc SW tests agrees with that
      measured in fixed gantry angle SW fields to within 0.02 mm. We also extracted the
      MLC leaf gaps during MLC travels in these dynamic arc SW deliveries from MLC
      positions recorded in dynalog files, and compared to the MLC gaps in fixed gantry
      SW fields. We found that MLC leaf gaps were maintained excellently constant
      whether in dynamic arc or fixed gantry angle SW delivery, with typical standard
      deviation of MLC gaps of only ~0.01mm for all involved leaf pairs. We believe
      these dynamic arc SW tests are very useful for checking MLC leaf constancy for
      RapidArc delivery.

PMID- 28516724
TI  - Poster - Thur Eve - 51: Three-dimensional in-vivo EPID dosimetry of IMRT and VMAT
      treatments.
AB  - As radiation treatment delivery becomes more complex, including dynamic IMRT and
      VMAT, the argument for routine patient dose verification becomes more compelling.
      This work demonstrates a technique that utilizes our pre-existing portal dose
      image prediction algorithm to compute 3D patient dose from recorded on-treatment
      portal images. This approach can be applied on CT simulation data or daily cone
      beam CT data sets. Here we demonstrate the robustness of our dose reconstruction
      technique with phantom and patient examples, with delivery schemes including IMRT
      and VMAT. For an example prostate treatment site, 3D dose distributions
      reconstructed in the patient model are computed for each fraction, and DVHs
      presented. Results indicate that the patient dose reconstruction algorithm
      compares well with treatment planning system computed doses for controlled test
      situations. For patient examples the 3D chi comparison values (similar to the
      gamma comparison) ranged from 94.5% to 100% agreement for voxels > 10% maximum
      dose for all treatments and phantom cases. We show an example where the DVH for
      fraction nine of a prostate treatment fails acceptability criteria, due to a
      previously unnoticed positioning error. Future work involves building our patient
      dose reconstruction into a QA package, subsequently integrating it into a
      clinical workflow. We are also investigating the use of this tool as a backbone
      for an in-house adaptive radiotherapy implementation. This work is supported by
      Varian Medical Systems.

PMID- 28516725
TI  - The need for better preventative strategies for inflammatory bowel disease
      patients at risk of herpes zoster virus.
AB  - BACKGROUND: Immunosuppressed inflammatory bowel disease (IBD) patients have an
      increased risk of herpes zoster virus (HZV) infection. The existing live
      attenuated HZV vaccine is contraindicated in some of these patients and can only
      be used with caution in others. AIMS: To describe characteristics of IBD patients
      suffering HZV to enable implementation of risk mitigation strategies for those at
      highest risk. METHODS: Gastroenterologists completed a proforma for IBD patients
      who experienced HZV infection: IBD phenotype, details of HZV infection,
      immunosuppression and any change to treatment upon diagnosis of HZV. RESULTS: A
      total of 30 cases was identified: Crohn disease (CD) (n = 25) and ulcerative
      colitis (n = 5). In total, 80% (20/25) of the CD patients had penetrating,
      stricturing or perianal disease. Time from commencement of immunosuppression to
      HZV infection was highly variable (range: 3 months to over 10 years). A total of
      90% (27/30) of patients was on at least one immunosuppressive therapy; of those,
      one-third was on monotherapy (9/27) and two-thirds (18/27) on dual therapy. A
      total of 89% (24/27) of immunosupressed patients was on a thiopurine
      (monotherapy; 6/27) or in combination (18/27). Complications of HZV occurred in
      27% (8/30) of patients. CONCLUSION: Our series is consistent with existing
      epidemiological analysis that identified more severe IBD and the use of multiple
      immunosuppressive therapies as risk factors for HZV. If the promise of an
      investigational subunit HZV vaccine is realised in immunocompromised patients,
      better protection may be possible in the future. Thiopurine medications were the
      most commonly used immunosuppressant in this series. Age and duration of
      immunosuppressive therapy do not appear to predict HZV infection.

PMID- 28516726
TI  - Clasper morphology of skates of the tribe Riorajini (Chondrichthyes: Rajiformes:
      Arhynchobatidae) and its systematic significance.
AB  - Claspers of adult specimens of the skate tribe Riorajini, family Arhynchobatidae,
      comprising Atlantoraja and Rioraja, are described, compared, and systematically
      reinterpreted based on material collected off southeastern and southern Brazil.
      For the first time the external components and musculature of the clasper of
      members of this tribe are described and related to internal (skeletal)
      structures. The component pecten is present in all species of Atlantoraja but
      absent in Rioraja. The new external component grip, an autapomorphy of A.
      cyclophora fully developed in adults, is described. Rioraja presents dorsal
      terminals 1 and 2, ventral marginal distally extended and ventral terminal
      cartilages. Dorsal terminals 1 and 2, ventral marginal distally extended,
      accessory terminals 2 and 3, and ventral terminal cartilages occur in
      Atlantoraja. A new interpretation of the ventral marginal distally extended is
      discussed. The dorsal terminal 1 of Atlantoraja has an inverted U shape but is
      triangular in Rioraja. The accessory terminal 2 cartilage is reported for the
      first time in Atlantoraja cyclophora. The accessory terminal 3 is present only in
      A. platana and A. cyclophora, and absent in Rioraja and A. castelnaui. Many of
      our findings concerning the clasper skeleton do not agree with previous
      interpretations. The arrangement, distribution and systematic significance of
      many of the terminal clasper components are discussed among rajoids.

PMID- 28516727
TI  - Non-invasive longitudinal monitoring of angiogenesis in a murine full-thickness
      cutaneous wound healing model using high-resolution three-dimensional ultrasound
      imaging.
AB  - BACKGROUND/PURPOSE: The aim of this study was to evaluate the longitudinal
      monitoring of angiogenesis in a murine full-thickness cutaneous wound healing
      model using high-resolution three-dimensional (3D) ultrasound imaging. METHODS:
      Two C57BL/6 mice were used. Two-dimensional (2D) ultrasound images with the Color
      Doppler mode were acquired at regular spatial intervals on day 9, 11, and 14
      after wounding. 3D ultrasound images were processed by reconstructing the 2D
      ultrasound image sequences. The wounds were harvested on day 14 and serial
      sections were immunohistologically stained with an anti-CD31 antibody. RESULTS:
      3D ultrasound imaging with the Color Doppler mode showed the distribution of
      microvascular growth on days 9, 11, and 14 after wounding (44.6%, 51.5%, and
      27.3% in wound 1, 55.8%, 38.1%, and 35.1% in wound 2, 60.6%, 62.6%, and 63.1% in
      wound 3, and 15.8%, 42.0%, and 31.9% in wound 4, respectively). A correlation was
      observed between % vascularity measured by paired 2D ultrasound imaging with the
      Color Doppler mode and sections immunohistologically stained for the anti-CD31
      antibody (r=0.927, 0.871, 0.717, and 0.913 for wounds 1, 2, 3, and 4,
      respectively. P<.01). CONCLUSION: These results indicate that high-resolution 3D
      ultrasound imaging is useful for longitudinally evaluating the distribution of
      microvascular growth over the course of healing.

PMID- 28516728
TI  - Increased heterogeneity of airway calibre in adult rats after hypoxia-induced
      intrauterine growth restriction.
AB  - BACKGROUND AND OBJECTIVE: Intrauterine growth restriction (IUGR) is associated
      with asthma development. We hypothesized that IUGR disrupts airway development
      leading to postnatal structural abnormalities of the airway that predispose to
      disease. This study therefore examined structural changes to the airway and lung
      in a rat model of maternal hypoxia-induced IUGR. METHODS: Pregnant rats were
      housed under hypoxic conditions (11.5% O2 ) from gestational days (GDs) 13 to 20
      (pseudoglandular-canalicular stages, i.e. period of airway development) and then
      returned to normoxic conditions (21% O2 ). A control group of pregnant rats was
      housed under normoxic conditions throughout pregnancy. Weights of male offspring
      were recorded at birth and 7 weeks of age (adulthood), at which point lungs were
      fixed for morphometry and stereology (n = 6/group), or bronchoalveolar lavage
      fluid (BALF) was collected for cell counts (n = 6/group). RESULTS: IUGR offspring
      were lighter at birth compared with control, but not at 7 weeks. While there was
      no difference in mean airway dimensions or lung volume, there was greater
      anatomical variation in airway lumen area in the IUGR group. A mathematical model
      of the human lung was used to show that greater heterogeneity in lumen area in
      IUGR-affected individuals increases bronchoconstriction during simulated
      bronchial challenge. More macrophages were identified in the BALF of IUGR
      offspring. CONCLUSION: The rat model demonstrates that IUGR leads to a more
      heterogeneous distribution of airway lumen calibre in adulthood with potential
      implications for bronchoconstriction in human subjects. Together with increased
      lung macrophages, these findings support a phenotypic shift after IUGR that may
      impact disease susceptibility.

PMID- 28516729
TI  - Proteome analysis of Duck Tembusu virus (DTMUV)-infected BHK-21 cells.
AB  - Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has
      caused huge economic losses to the duck industry in China since 2010. Moreover,
      the infection has spread rapidly, posing a potential public health concern. In
      this study, iTRAQ approach was first used to quantitatively identify
      differentially expressed cellular proteins in DTMUV-infected BHK-21 cells which
      are usually employed to produce veterinary vaccines for DTMUV, as well as other
      flaviviruses by serial passage. We identified 192 differentially expressed
      cellular proteins, including 11 upregulated and eight downregulated proteins at
      24 h postinfection (hpi), as well as 25 upregulated and 151 downregulated
      proteins at 48 hpi, of which TLR9, DDX3X, and DDX5 may play important roles in
      virus propagation. Further, DDX3X could inhibit DTMUV replication by modulating
      the IFN pathway via TBK1. In conclusion, our study is the first to analyze the
      protein profile of DTMUV-infected cells by quantitative proteomics. We believe
      that our findings provide valuable information in better understanding the host
      response to DTMUV infection. These findings are particularly important in the
      development of vaccine-based strategies.

PMID- 28516730
TI  - Control of Pseudomonas mastitis on a large dairy farm by using slightly acidic
      electrolyzed water.
AB  - The disinfection effect of slightly acidic electrolyzed water (SAEW) use in a
      farm where Pseudomonas mastitis has spread was evaluated. Despite the application
      of antibiotic therapy and complete cessation of milking infected quarters,
      numerous new and recurrent Pseudomonas aeruginosa clinical mastitis infections
      (5.8-7.1% of clinical mastitis cases) occurred on the farm from 2003 to 2005.
      Procedural changes and equipment modifications did not improve environmental
      contamination or the incidence of Pseudomonas mastitis. To more thoroughly
      decontaminate the milking parlor, an SAEW system was installed in 2006. All
      milking equipment and the parlor environment were sterilized with SAEW (pH 5-6.5,
      available chlorine 12 parts per million) before and during milking time. After
      adopting the SAEW system, the incidence of clinical and subclinical Pseudomonas
      mastitis cases decreased significantly (P < 0.0001) and disappeared. These
      findings suggest that SAEW effectively reduced the incidence of mastitis in a
      herd contaminated by Pseudomonas species. This is the first report to demonstrate
      the effectiveness of disinfection by SAEW against mastitis pathogens in the
      environment.

PMID- 28516731
TI  - Alopecia areata - hyperactivity of the hypothalamic-pituitary-adrenal axis is a
      myth?
AB  - INTRODUCTION: Psychological stress is known to cause exacerbation of different
      skin pathologies including alopecia areata (AA). A hyperactivity of the
      hypothalamic-pituitary-adrenal axis (the HPA axis) in patients affected by AA (AA
      patients) was proposed to be a neuroendocrine response to stress. Still little is
      known about melanocyte-stimulating hormone (MSH) and cortisol production in AA
      settings. AIM: The aim of the study was to compare trends in a production of MSH
      and cortisol in patients with AA patients and healthy controls. MATERIAL AND
      METHODS: Plasma concentrations of free cortisol and MSH were measured in 43 AA
      patients (35.5 +/- 10.6 years) and 37 healthy subjects (35.9 +/- 10.5 years)
      selected from the Dermatology Outpatient Clinic at Medical University of Silesia
      in Katowice, Poland. Results were submitted to statistical analysis with Shapiro
      Wilk W-test and subsequently nonparametric (Mann-Whitney U-test) or parametric
      (Student's t-test) statistics were performed. RESULTS: Mean plasma level of MSH
      was 5.39 ng/mL in AA patients and 5.71 ng/mL in healthy controls. The difference
      between groups was non-significant (P = 0.435), but the control group manifested
      higher values of MSH (Q75 = 13.6 ng/mL vs Q75 = 5.98 ng/mL) and this tendency was
      especially stronger in females. AA patients had greater mean plasma level of
      cortisol (157.63 +/- 91.16 ug/L) than healthy controls (123.32 +/- 71.28 ug/L);
      however, the difference between them was also non-significant (P = 0.063). No sex
      dependent tendency to a greater production of cortisol was found. CONCLUSIONS:
      Expectations of disturbances in production of MSH and cortisol were not
      fulfilled. Neither MSH nor cortisol plasma levels appear to be clearly changed in
      AA patients.

PMID- 28516732
TI  - Diadenosine tetraphosphate (Ap4A) - an E. coli alarmone or a damage metabolite?
AB  - Under stress, metabolism is changing: specific up- or down-regulation of proteins
      and metabolites occurs as well as side effects. Distinguishing specific stress
      signaling metabolites (alarmones) from side products (damage metabolites) is not
      trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of
      aminoacyl-tRNA synthetases found in all domains of life. The earliest
      observations suggested that Ap4A serves as an alarmone for heat stress in
      Escherichia coli. However, despite 50 years of research, the signaling mechanisms
      associated with Ap4A remain unknown. We defined a set of criteria for
      distinguishing alarmones from damage metabolites to systematically classify Ap4A.
      In a nutshell, no indications for a signaling cascade that is triggered by Ap4A
      were found; rather, we found that Ap4A is efficiently removed in a constitutive,
      nonregulated manner. Several fold perturbations in Ap4A concentrations have no
      effect, yet accumulation at very high levels is toxic due to disturbance of zinc
      homeostasis, and also because Ap4A's structural overlap with ATP can result in
      spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all
      criteria for a damage metabolite. While we do not exclude any role in signaling,
      our results indicate that the damage metabolite option should be considered as
      the null hypothesis when examining Ap4A and other metabolites whose levels change
      upon stress.

PMID- 28516733
TI  - The interactive role of eating regulation and stress in the prediction of weight
      related outcomes among college students.
AB  - The interactive role of eating regulation and perceived stress on weight-related
      outcomes was examined among 319 sophomore year college students (110 males and
      209 females). Moderated regressions were used to examine interactions between
      stress and eating regulation on study outcomes including body mass index (BMI)
      and body fat. Eating regulation moderated associations between stress and BMI and
      body fat outcomes. Students reporting high perceived stress, high autonomous
      eating regulation, low controlled regulation, and low amotivation exhibited
      higher outcomes (BMI and body fat) than those with similar eating regulation but
      lower perceived stress. Students with lower autonomous eating regulation and
      higher controlled regulation had no differences in study outcomes across levels
      of stress. College students who regulate their eating behaviours for health
      reasons (specifically showing autonomous regulation) exhibit higher BMI and body
      fat when they report higher levels of perceived stress. Health promotion programs
      for college students need to target education efforts towards stress reduction
      and healthy eating behaviours.

PMID- 28516734
TI  - Does co-occurring borderline personality disorder influence acute phase treatment
      for first-episode psychosis?
AB  - BACKGROUND: This aims of this study were: (1) to determine the prevalence of co
      occurring borderline personality disorder (BPD) in a first-episode psychosis
      (FEP) sample; (2) to determine differences between patients with and without BPD
      on demographics, comorbidities and clinical risks and other variables; and (3) to
      examine whether BPD comorbidity influenced treatment received by patients for FEP
      during their first 3 months after service entry to a specialist early psychosis
      service. METHODS: A file audit was conducted for 100 consecutive admissions to an
      early psychosis service. Patients with a clinician-rated co-occurring diagnosis
      of BPD were compared with patients without clinician-rated BPD on a range of
      variables. RESULTS: Twenty-two percent of the FEP sample was diagnosed with co
      occurring BPD by clinician ratings. The FEP group with co-occurring BPD was found
      to be younger, more likely to have other comorbidities, and were at higher risk
      of suicide and violent behaviour. Group differences were found in treatment
      received for FEP, whereby patients with co-occurring BPD had poorer access to
      standard treatment, including guideline concordant antipsychotic medication
      prescription. CONCLUSION: Young people with co-occurring clinician-rated BPD and
      FEP experienced greater difficulty accessing standard care for FEP and received
      relatively different treatment, including different pharmacotherapy, compared
      with those FEP patients without BPD. There is a need to develop new clinical
      guidelines and effective treatments for this specific subgroup with early
      psychosis and co-occurring BPD that take into account interpersonal and
      "premorbid" aspects of their presenting problems.

PMID- 28516735
TI  - Assessment of trophic ecomorphology in non-alligatoroid crocodylians and its
      adaptive and taxonomic implications.
AB  - Although the establishment of trophic ecomorphology in living crocodylians can
      contribute to estimating feeding habits of extinct large aquatic reptiles,
      assessment of ecomorphological traits other than the snout shape has scarcely
      been conducted in crocodylians. Here, I tested the validity of the proposed
      trophic ecomorphological traits in crocodylians by examining the correlation
      between those traits and the snout shape (an established trophic ecomorphology),
      using 10 non-alligatoroid crocodylian species with a wide range of snout shape. I
      then compared the ontogenetic scaling of trophic ecomorphology to discuss its
      adaptive and taxonomic significance. The results demonstrated that degree of
      heterodonty, tooth spacing, size of supratemporal fenestra (STF), ventral
      extension of pterygoid flange and length of lower jaw symphysis are significantly
      correlated with snout shape by both non-phylogenetic and phylogenetic regression
      analyses. Gavialis gangeticus falls outside of 95% prediction intervals for the
      relationships of some traits and the snout shape, suggesting that piscivorous
      specialization involves the deviation from the typical transformation axis of
      skull characters. The comparative snout shape ontogeny revealed a universal trend
      of snout widening through growth in the sampled crocodylians, implying the
      existence of a shared size-dependent biomechanical constraint in non-alligatoroid
      crocodylians. Growth patterns of other traits indicated that G. gangeticus shows
      atypical trends for degree of heterodonty, size of STF, and symphysis length,
      whereas the same trends are shared for tooth spacing and ventral extension of
      pterygoid flange among non-alligatoroid crocodylians. These suggest that some
      characters are ontogenetically labile in response to prey preference shifts
      through growth, but other characters are in keeping with the conserved
      biomechanics among non-alligatoroid crocodylians. Some important taxonomic
      characters such as the occlusal pattern are likely correlated with ontogeny and
      trophic ecomorphology rather than are constrained by phylogenetic relationships,
      and careful reassessment of such characters might be necessary for better
      reconstructing the morphological phylogeny of crocodylians.

PMID- 28516736
TI  - Inorganic Colloidal Perovskite Quantum Dots for Robust Solar CO2 Reduction.
AB  - Inorganic perovskite quantum dots as optoelectronic materials have attracted
      enormous attention in light-harvesting and emitting devices. However,
      photocatalytic conversion based on inorganic perovskite halides has not been
      reported. Here, we have synthesized colloidal quantum dots (QDs, 3-12 nm) of
      cesium lead halide perovskites (CsPbBr3 ) as a new type of photocatalytic
      material. The band gap energies and photoluminescence (PL) spectra are tunable
      over the visible spectral region according to quantum size effects on an atomic
      scale. The increased carrier lifetime revealed by time-resolved PL spectra,
      indicates the efficient electron-hole separation and transfer. As expected, the
      CsPbBr3 QDs with high selectivity of greater than 99 % achieve an efficient yield
      of 20.9 MUmol g-1 towards solar CO2 reduction. This work has opened a new avenue
      for inorganic colloidal perovskite materials as efficient photocatalysts to
      convert CO2 into valuable fuels.

PMID- 28516738
TI  - Intrinsic fluorescence and mechanical testing of articular cartilage in human
      patients with osteoarthritis.
AB  - The degeneration of articular cartilage is the main cause of osteoarthritis (OA),
      a common cause of disability among elderly patients. The aim of this study is to
      understand the correlation between intrinsic fluorescence of articular cartilage
      and its biomechanical properties in patients with osteoarthritis. Cylindrical
      samples of articular cartilage 6 mm in diameter were extracted via biopsy punch
      from the femoral condyles of 6 patients with advanced OA undergoing knee
      replacement surgery. The mechanical stiffness and fluorescence of each cartilage
      plug were measured by indentation test and spectrofluorometry. Maps of
      fluorescence intensity, at excitation/emission wavelengths of 240-520/290-530 nm,
      were used to identify wavelengths of interest. The mechanical stiffness and
      fluorescence intensity were correlated using a Spearman analysis. The
      excitation/emission maps demonstrated three fluorescence peaks at
      excitation/emission wavelength pairs 330/390, 350/430 and 370/460 nm. The best
      correlation between the fluorescence intensity and stiffness of cartilage was
      obtained for the 330 nm excitation band [R=0.82, p=0.04]. The intrinsic
      fluorescence of articular cartilage may have application in optically assessing
      the state of cartilage in patients with osteoarthritis.

PMID- 28516737
TI  - Iron status and inflammatory biomarkers in patients with acutely decompensated
      heart failure: early in-hospital phase and 30-day follow-up.

PMID- 28516739
TI  - Treatment of Propriospinal Myoclonus at Sleep Onset.

PMID- 28516740
TI  - Toxic Leukoencephalopathy and Hypokalemia Due to Exposure to Trimethyltin.

PMID- 28516742
TI  - A Mutation in the ACTA1 gene Manifesting Nemaline Myopathy with Central Nervous
      System Lesions.

PMID- 28516741
TI  - Letter to the Editor: Asymmetric and Upper-Body Parkinsonism in Patients with
      Idiopathic Normal-Pressure Hydrocephalus.

PMID- 28516743
TI  - A Novel APTX Variant and Ataxia with Oculomotor Apraxia Type 1.

PMID- 28516744
TI  - Repetitive Nerve Stimulation in MuSK-Antibody-Positive Myasthenia Gravis.
AB  - BACKGROUND AND PURPOSE: Responses to repetitive nerve stimulation (RNS) in
      patients with muscle-specific tyrosine kinase (MuSK) antibody (Ab)-positive
      myasthenia gravis (MG) vary depending on the muscles tested. We analyzed the RNS
      responses of limb and facial muscles in MuSK-Ab-positive and acetylcholine
      receptor (AChR)-Ab-negative MG (MuSK MG) and MuSK-Ab-negative and AChR-Ab
      negative [double-seronegative (DSN)] MG patients. METHODS: We retrospectively
      compared RNS responses between 45 MuSK MG and 29 DSN MG. RNS was applied to the
      abductor digiti minimi, flexor carpi ulnaris, trapezius, orbicularis oculi, and
      nasalis muscles. RESULTS: Abnormal RNS responses in limb muscles were observed in
      22.2 and 58.6% of MuSK MG and DSN MG patients, respectively, with abnormal facial
      responses observed in 77.8 and 65.5%, and abnormal responses observed in any of
      the five muscles in 86.7 and 72.4%. Abnormal RNS responses in the abductor digiti
      minimi or flexor carpi ulnaris were less frequent in MuSK MG (8.9 and 15.6%,
      respectively) than in DSN MG (37.9 and 55.2%), whereas the findings for other
      muscles were not significantly different between the groups. Abnormal facial
      responses but normal limb responses were independently associated with MuSK MG
      (odds ratio=5.224, 95% confidence interval=1.300-20.990). CONCLUSIONS: Abnormal
      RNS responses primarily in facial muscles without involvement of limb muscles
      were more pronounced in MuSK MG than in DSN MG. RNS of both facial and limb
      muscles in AChR-Ab-negative MG can increase the test sensitivity and aid in early
      suspicion of MuSK MG.

PMID- 28516745
TI  - Gerstmann's Syndrome Associated with Right Parietal Hemorrhage and Arteriovenous
      Malformation.

PMID- 28516746
TI  - Vasculitis Findings for the Anterior Choroidal Artery in 3D-Time-of-Flight
      Magnetic Resonance Angiography.

PMID- 28516747
TI  - The History of Growth Hormone Treatment for GHD in Japan.
AB  - In Japan, treatment of growth hormone deficiency with pituitary-extracted human
      growth hormone (phGH) was covered by health insurance for the first time in 1975.
      However, because of the shortage of phGH, the Foundation for Growth Science (FGS)
      was founded in 1977 to control the use of the product by its registration system
      and to collect pituitary glands in Japan. In 1986, recombinant human growth
      hormone was first approved. Since then, the FGS has been involved in the
      harmonization of growth hormone measurement, assessment for treatment eligibility
      according to the diagnostic criteria by the research group of the Ministry of
      Health and Welfare, and database generation and its utilization.

PMID- 28516748
TI  - Standardization of Growth Hormone and Insulin-like Growth Factor-I Measurements.
AB  - Measurement of the levels of growth hormone (GH) and its related factor insulin
      like growth factor I (IGF-I) is essential for the diagnosis and treatment of GH
      deficiency (GHD) and conditions related to excess GH such as acromegaly and
      pituitary gigantism. Measurement of GH levels is also used as an indicator of
      hypothalamic-pituitary function. Because of the marked variability in GH
      measurements among kits, the Study Committee for GH and Its Related Factors of
      The Foundation for Growth Science, Japan standardized GH values measured with
      various commercially available GH assay kits in Japan. The committee also
      established IGF-I reference values for Japanese subjects of all ages, from
      childhood to adulthood. Hopefully, international harmonization of GH measurements
      will be achieved in the future.

PMID- 28516750
TI  - Quality of Life of SGA Children with Short Stature Receiving GH Treatment in
      Japan.
AB  - The objective of this study was to compare the quality of life (QOL) of small for
      gestational age (SGA) children with short stature with that of children with
      normal height, and examine the effects of growth hormone (GH) treatment on the
      QOL of the SGA children using questionnaires administered to their parents or
      guardians. The results showed that QOL in daily living of SGA children with short
      stature was lower than that of normal children based on the perceptions of their
      parents or guardians. In addition, GH treatment improved the physical domain of
      QOL of SGA children with short stature. This study suggests that GH treatment can
      improve QOL and reduce psychosocial problems related to short stature.

PMID- 28516749
TI  - International Comparison of Adult Height in Children with Growth Hormone
      Deficiency and Limitations of Growth Hormone Treatment in Japan.
AB  - The approved therapeutic dose of growth hormone (GH) for growth hormone
      deficiency (GHD) varies depending on the country. Japan has the lowest
      therapeutic dose globally, with a single dose of 0.175 mg/kg/week. GH treatment
      for GHD is considered as a replacement therapy and in fact, a dose of 0.175
      mg/kg/week is slightly higher than GH secretion in prepubertal healthy children
      but nearly the same as that of pubertal children. Although the same growth rate
      as that of healthy children is expected in response to replacement therapy, the
      catch-up growth observed for the first 1 to 2 years of GH treatment was
      misinterpreted as an effect of the GH replacement therapy. The real effect of the
      GH replacement therapy was the growth rate appeared after more than 3 years of GH
      therapy, when patients showed nearly the same growth rate as healthy children.
      Therefore, children with GHD can have a higher growth rate than healthy children
      only for the first 1 to 2 years of GH therapy, after which their growth rate
      begins to wane. In the United States and Europe, the various therapeutic doses
      and high-dose treatment are accepted and the SD score of adult height after
      treatment is higher than that in Japan. The improvement degree of the height SD
      score and the adult height SD score with GH therapy are lower in Japan compared
      with other countries that administer a similar therapeutic dose. This suggests
      that the response to GH can be affected by race. Actual comparison of the
      response to GH between Japanese and Caucasian patients using KIGS (Pharmacia
      International Growth Database) data showed that both the short-term response and
      the effect on adult height were reduced in Japanese patients. As there is a
      strong positive correlation between adult height and height at the onset of
      puberty, treatment methods that can increase pubertal growth will be considered
      in the future for patients with GDH who enter puberty with short stature.

PMID- 28516751
TI  - Growth Hormone Therapy and Brain Tumors.
AB  - As one of the projects of the Adverse Events Study Group of the Foundation for
      Growth Science in Japan, the literatures on the recurrence and / or regrowth or
      new formation of brain tumors in patients treated with growth hormone (GH) were
      reviewed. Since the tumor volume of the sellar lesion can be accurately evaluated
      only by magnetic resonance imaging (MRI), the related literatures published after
      1990 were retrieved by searching under keywords, such as GH, replacement therapy,
      brain tumor, recurrence, tumor formation, etc. It is undeniable that GH therapy
      may result in tumor enlargement only in a very small percentage of cases.
      However, within a scientifically reliable range of confirmation with large-scale
      researches and case-control studies, it can be considered that there is no
      relation between GH therapy and the recurrence or new formation of brain tumors.

PMID- 28516752
TI  - Growth Hormone Treatment and Adverse Events.
AB  - We compiled the major adverse events included in the Annual Research Reports of
      the Foundation for Growth Research published in and after 2000. We conducted a
      review of approximately 32,000 patients treated with growth hormone (GH) who
      subsequently developed leukemia and who were registered with the Foundation for
      Growth Research (from 1975 to December 31 1997). We performed a literature review
      and found that GH therapy was not associated with leukemia onset in patients with
      no risk factors for leukemia. We also reported the onset of diabetes mellitus
      (DM), scoliosis, and respiratory problems in patients with Prader-Willi syndrome
      who were treated with GH. Osteoporosis, Hashimoto thyroiditis, and hyperlipemia
      were relatively frequent complications of Turner syndrome (TS).

PMID- 28516753
TI  - Revision of the Growth References for Japanese Girls with Turner Syndrome.

PMID- 28516754
TI  - Adult Height in Patients with Turner Syndrome and Association with Lifestyle
      related Diseases after Human Growth Hormone Treatment in Japan.

PMID- 28516755
TI  - Iodine and Thyroid Function: A Historical Review of Goiter and the Current Iodine
      Status in Japan.

PMID- 28516757
TI  - Gastric Perforation Caused by an Intragastric Balloon: Endoscopic Findings.
AB  - Intragastric balloon (IGB) insertion has been most frequently used in the West as
      an effective endoscopic treatment for morbid obesity, in practice. Recently,
      there is a growing number of cases requiring IGB deployment for obesity treatment
      in Korea. One of the reported complications of IGB use is gastric perforation. A
      47-year-old woman was admitted to the hospital with mild symptoms, 7 weeks after
      having an IGB placed. Esophagogastroduodenoscopy was performed and gastric ulcer
      perforation was observed in the ulcer base, where food particles were impacted.
      Laparoscopic primary repair was done successfully. This was a case of gastric
      perforation, secondary to poor compliance with a proton-pump inhibitor (PPI). PPI
      and Helicobacter pylori eradication are important for ulcer prevention following
      IGB deployment.

PMID- 28516756
TI  - Carbon Dioxide versus Air Insufflation in Gastric Endoscopic Submucosal
      Dissection: A Systematic Review and Meta-Analysis of Randomized Controlled
      Trials.
AB  - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) with air insufflation is
      commonly used for the staging and treatment of early gastric carcinoma. However,
      carbon dioxide (CO2) use has been shown to cause less post-procedural pain and
      fewer adverse events. The objective of this study was to compare the post
      procedural pain and adverse events associated with CO2 and air insufflation in
      ESD. METHODS: A systematic search was conducted for randomized control trials
      (RCTs) comparing the two approaches in ESD. The Mantel-Haenszel method was used
      to analyze the data. The mean difference (MD) and odds ratio (OR) were used for
      continuous and categorical variables, respectively. RESULTS: Four RCTs with a
      total of 391 patients who underwent ESD were included in our meta-analysis. The
      difference in maximal post-procedural pain between the two groups was
      statistically significant (MD, -7.41; 95% confidence interval [CI], -13.6 - 
      1.21; p=0.020). However, no significant differences were found in the length of
      procedure, end-tidal CO2, rate of perforation, and postprocedural hemorrhage
      between the two groups. The incidence of overall adverse events was significantly
      lower in the CO2 group (OR, 0.51; CI, 0.32-0.84; p=0.007). CONCLUSIONS: CO2
      insufflation in gastric ESD is associated with less post-operative pain and
      discomfort, and a lower risk of overall adverse events compared with air
      insufflation.

PMID- 28516759
TI  - Reduced Graphene Oxide-Wrapped Nickel-Rich Cathode Materials for Lithium Ion
      Batteries.
AB  - The encapsulation of Ni-rich cathode materials (LiNi0.6Co0.2Mn0.2O2) for lithium
      ion batteries in reduced graphene oxide (rGO) sheets is introduced to improve
      electrochemical performances. Using (3-aminopropyl)triethoxysilane, the active
      materials are completely wrapped with several rGO layers of ~2 nm thickness. By
      virtue of the great electrical conductivity of graphene, the rGO-coated cathode
      materials exhibit much enhanced electrochemical performances of cycling property
      and rate capability. In addition, it is shown that the structural degradation of
      the active materials, which is from the rhombohedral layered structure (R3m) to
      the spinel (Fd3m) or rock-salt phase (Fm3m), is significantly reduced as well as
      delayed due to the protection of the active materials in the rGO layers from
      direct contact with electrolytes and the consequent suppression of side
      reactions.

PMID- 28516760
TI  - From Highly Fluorescent Donors to Strongly Absorbing Acceptors: The Tunable
      Properties of Fluorubines.
AB  - The synthesis and characterization of three novel fluorubine derivatives is
      reported via three to four simple reaction steps with isolatable intermediates.
      The functional dyes are characterized by their strong absorption peaks in the
      visible region and their high fluorescence quantum yields. A significant and
      useful feature is that the properties can be tuned over a wide range by changing
      the pH. Transformation of the dyes into protonated amidinium salts leads to
      narrower band gaps and to drastically lower LUMO energies. Further reduction of
      the pH results in the doubly protonated species with a high electron-deficiency
      and LUMO energies of -4.8 eV, bathochromic shifts, and a strong intensity
      increase of up to epsilon = 120 000 M-1 cm-1.

PMID- 28516758
TI  - Necrotizing Pancreatitis: Current Management and Therapies.
AB  - Acute necrotizing pancreatitis accounts for 10% of acute pancreatitis (AP) cases
      and is associated with a higher mortality and morbidity. Necrosis within the
      first 4 weeks of disease onset is defined as an acute necrotic collection (ANC),
      while walled off pancreatic necrosis (WOPN) develops after 4 weeks of disease
      onset. An infected or symptomatic WOPN requires drainage. The management of
      pancreatic necrosis has shifted away from open necrosectomy, as it is associated
      with a high morbidity, to less invasive techniques. In this review, we summarize
      the current management and therapies for acute necrotizing pancreatitis.

PMID- 28516761
TI  - Facile and Sensitive Near-Infrared Fluorescence Probe for the Detection of
      Endogenous Alkaline Phosphatase Activity In Vivo.
AB  - Alkaline phosphatase (ALP) is an essential enzyme and widely distributes in a
      variety of tissues. To date, various nanomaterial and small-molecule fluorescent
      probes for ALP have been constructed successfully, but the emission wavelengths
      of these probes are in the ultraviolet or visible range, which is not beneficial
      for bioimaging. Herein, a hemicyanine-based near-infrared (NIR) fluorescent probe
      named CyP is first synthesized and used to detect ALP activity. The
      characteristics of probe CyP are as follows: (1) The probe possesses a facile
      structure, which can be obtained by easy synthetic steps. (2) The fluorescence
      emission of the sensing system is at 738 nm belonging to NIR region, which is
      suitable for bioimaging in vivo. (3) The probe exhibits high sensitivity to ALP
      with 10-fold fluorescence enhancement and low detection limit (0.003 U/mL) can
      match the level of ALP in vivo. (4) The fluorescent change of the probe is
      attributed to the fact that ALP-catalyzed cleavage of the phosphate group in CyP
      induces the transformation of CyP (fluorescence off) into CyOH (fluorescence on),
      which is proved by HPLC, 31P NMR, MS, and DFT calculation. (5) The NIR
      fluorescent probe is applied for the detection of endogenous ALP activity in
      various biological samples such as cell, tissue, and living animal with
      satisfactory results.

PMID- 28516762
TI  - Organophosphorus Flame Retardants in Pregnant Women and Their Transfer to
      Chorionic Villi.
AB  - The potential for prenatal exposure has recently raised concerns over the health
      risks of endocrine disruptors; however, knowledge about human prenatal exposure
      to organophosphorus flame retardants (OPFRs) is lacking. In this study, 2
      ethylhexyl diphenyl phosphate (EHDPP), tributyl phosphate (TBP), triphenyl
      phosphate (TPHP), and tris(2-chloroethyl) phosphate (TCEP) were detected in the
      majority of chorionic villus samples, with median concentrations of 13.6, 18.8,
      11.1, and 0.51 ng/g of dry weight (dw), respectively, significantly higher than
      those in the matching maternal decidua samples (5.96, 10.8, 1.44, and 0.26 ng/g
      of dw, respectively). The ratios of concentrations in chorionic villi (containing
      embryos) to those in maternal deciduae (CMRs) were 4.17, 3.82, 2.81, and 2.00 for
      EHDPP, TPHP, TBP, and TCEP, respectively, which correlated with their log Kow
      values (p = 0.003). The results of transthyretin (TTR) binding assays indicated
      that the stronger the binding ability to TTR, the higher the CMRs. The median
      concentrations of the metabolites diphenyl phosphate (DPHP), dibutyl phosphate
      (DBP), and bis(2-chloroethyl) phosphate (BCEP) were 4.11, 429, and 157 ng/g of dw
      in chorionic villi, higher than those in deciduae (1.64, 181, and 25.4 ng/g of
      dw, respectively). The ratios of DPHP/TPHP and DPHP/EHDPP were 0.20 and 0.43 in
      chorionic villi and 1.24 and 2.03 in deciduae, respectively, much lower than
      those of DBP/TBP and BCEP/TCEP (20.9 and 165.6 in chorionic villi and 13.1 and
      35.3 in deciduae, respectively), suggesting that the difference in metabolism
      between the deciduae and chorionic villi would affect their maternal transfer.

PMID- 28516763
TI  - First Assessment of NOx Sources at a Regional Background Site in North China
      Using Isotopic Analysis Linked with Modeling.
AB  - Nitrogen oxides (NOx, including NO and NO2) play an important role in the
      formation of atmospheric particles. Thus, NOx emission reduction is critical for
      improving air quality, especially in severely air-polluted regions (e.g., North
      China). In this study, the source of NOx was investigated by the isotopic
      composition (delta15N) of particulate nitrate (p-NO3-) at Beihuangcheng Island
      (BH), a regional background site in North China. It was found that the delta15N
      NO3- (n = 120) values varied between -1.70/00 and +24.00/00 and the delta18O-NO3-
      values ranged from 49.40/00 to 103.90/00. On the basis of the Bayesian mixing
      model, 27.78 +/- 8.89%, 36.53 +/- 6.66%, 22.01 +/- 6.92%, and 13.68 +/- 3.16% of
      annual NOx could be attributed to biomass burning, coal combustion, mobile
      sources, and biogenic soil emissions, respectively. Seasonally, the four sources
      were similar in spring and fall. Biogenic soil emissions were augmented in summer
      in association with the hot and rainy weather. Coal combustion increased
      significantly in winter with other sources showing an obvious decline. This study
      confirmed that isotope-modeling by delta15N-NO3- is a promising tool for
      partitioning NOx sources and provides guidance to policymakers with regard to
      options for NOx reduction in North China.

PMID- 28516765
TI  - Peptide Microarray-Based Metal Enhanced Fluorescence Assay for Multiple Profiling
      of Matrix Metalloproteinases Activities.
AB  - Matrix metalloproteinases (MMPs) are closely associated with cancer cell invasion
      and metastasis. Herein, a fluorescence resonance energy transfer (FRET)-peptide
      microarray-based metal enhanced fluorescence (MEF) assay is proposed for multiple
      and sensitive profiling of MMPs activities on a novel Au/Ag@SiO2 substrate. The
      Au/Ag@SiO2 substrate is prepared by electroless deposition of silver on gold
      nanoparticle (GNP) seeds, followed by SiO2 shell coating and surface
      functionalization. The specific FRET peptides are spotted on the Au/Ag@SiO2
      substrate to sensitively detect MMPs (MMP-2, -3, -7, -9, -14) via fluorescence
      recovery by the MMP cleavage of quenched peptide motifs and further enhanced by
      MEF. Under the optimal conditions, the limits of detection are 12.2 fg mL-1 for
      MMP-2, 60 pg mL-1 for MMP-3, 0.22 pg mL-1 for MMP-7, 102 fg mL-1 for MMP-9, and
      0.68 ng mL-1 for MMP-14, respectively. The practicability of the FRET-peptide
      microarray-based MEF assay is demonstrated by profiling of multiplexed MMPs
      activities in various cell lines and clinical thyroid tissue samples of papillary
      thyroid carcinoma (PTC) patients and thyroid nodules (TN) patients, and
      satisfactory results are obtained.

PMID- 28516766
TI  - In Situ Generated TEMPO Oxoammonium Salt Mediated Tandem Cyclization of beta
      Oxoamides with Amine Hydrochlorides for the Synthesis of Pyrrolin-4-ones.
AB  - A novel in situ generated TEMPO oxoammonium salt mediated one-pot tandem reaction
      has been developed for the straightforward construction of pyrrolin-4-ones from
      readily available beta-oxoamides with amine hydrochlorides. The reaction
      tolerates various functional groups and represents a reliable method for the
      synthesis of highly substituted pyrrolin-4-ones in good yields under mild
      conditions. Detailed mechanistic studies disclosed that TEMPO oxoammonium salt
      generated in situ was crucial for the transformation involving the formation of
      enaminone precursors in situ by condensation of the beta-oxoamides with amines,
      followed by sequential oxidative coupling with beta-oxoamides, intramolecular
      cyclization, and 1,2-alkyl migration steps.

PMID- 28516764
TI  - An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2
      Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid
      Recognition.
AB  - Pleckstrin homology (PH) domains are well-known as phospholipid binding modules,
      yet evidence that PH domain function extends beyond lipid recognition is
      mounting. In this work, we characterize a protein binding function for the PH
      domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific
      signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases.
      Its N-terminal PH domain is a well-characterized lipid binding module that
      localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP3)
      binding. Using a combination of nuclear magnetic resonance spectroscopy and
      mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK
      PH domain that makes direct contact with the catalytic kinase domain of ITK,
      inhibiting the phospho-transfer reaction. Moreover, we have elucidated an
      important interplay between lipid binding by the ITK PH domain and the stability
      of the autoinhibitory complex formed by full length ITK. The ITK activation loop
      in the kinase domain becomes accessible to phosphorylation to the exogenous
      kinase LCK upon binding of the ITK PH domain to PIP3. By clarifying the
      allosteric role of the ITK PH domain in controlling ITK function, we have
      expanded the functional repertoire of the PH domain generally and opened the door
      to alternative strategies to target this specific kinase in the context of immune
      cell signaling.

PMID- 28516767
TI  - Synthesis and Structure of 3,3-Dimethylindoline Squaraine Rotaxanes.
AB  - Squaraine rotaxanes are mechanically interlocked molecules comprised of a
      dumbbell shaped squaraine dye inside a tetralactam macrocycle. Previous squaraine
      rotaxanes have employed planar squaraine dyes with 4-aminophenyl, 2
      aminothiophene, or N-amino units appended to the central C4O2 core. Here we
      describe two rotaxanes that encapsulate a 3,3-dimethylindoline squaraine inside a
      tetralactam with anthracene sidewalls. The rotaxanes were prepared by a templated
      clipping reaction and an X-ray crystal structure shows that the squaraine gem
      dimethyl groups force a relatively wide separation between the macrocycle
      anthracene sidewalls. The decreased interaction between the encapsulated
      squaraine and the anthracene sidewalls leads to a smaller red shift of the
      squaraine absorption and emission bands. Solution-state studies show that the gem
      dimethyl groups in 3,3-dimethylindoline squaraine dyes are large enough to
      prevent macrocycle threading or rotaxane unthreading. One of the new rotaxanes
      emits an orange light (560-650 nm), and there is a 10-fold enhancement in the
      squaraine fluorescence quantum yield upon encapsulation as a rotaxane. This
      orange-emitting dye completes the palette of known squaraine rotaxane
      fluorophores whose emission profiles span the color range from green to near
      infrared.

PMID- 28516768
TI  - Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd3N@C80: A New Theranostic
      Agent for Combating Oxidative Stress and Resolving Inflammation.
AB  - Antioxidative and anti-inflammatory effects of trimetallic nitride endohedral
      fullerenes carboxyl-Gd3N@C80, a newly developed magnetic resonance imaging (MRI)
      contrast agent, were investigated. All hydrochalarone and carboxyl-functionalized
      fullerenes showed effective radical (hydroxyl and superoxide anion) scavenging,
      whereas the carboxyl-Gd3N@C80 more efficiently attenuated lipopolysaccharide
      (LPS) induced oxidative stress in macrophages. Carboxyl-Gd3N@C80 also suppressed
      LPS-elicited mRNA expression of pro-inflammatory inducible nitric oxide synthase
      and tumor necrosis factor-alpha, and upregulated antioxidative enzyme axis Nrf2
      and heme oxygenase-1, possibly via ERK but not AKT signaling pathways. Therefore,
      carboxyl-Gd3N@C80 held a great promise in becoming a novel theranostic
      nanoplatform for simultaneously deliver MRI contrast and therapeutic functions to
      inflammation-related diseases.

PMID- 28516769
TI  - Identification of Rotundone as a Potent Odor-Active Compound of Several Kinds of
      Fruits.
AB  - An investigation of the aromas of grapefruit, orange, apple, and mango revealed
      the presence of an odor-active compound that gave off a strong woody odor when
      assessed by gas chromatography-olfactometry. We isolated the compound from a high
      boiling fraction of an orange essential oil, and subsequent nuclear magnetic
      resonance analyses of the isolated compound identified it as rotundone. Mass
      spectra and retention indices obtained from aroma concentrates of grapefruit,
      apple, and mango were identical to those of rotundone, which was therefore
      determined to be the common woody compound in these fruits. Sensory analyses were
      performed to assess the effects of rotundone on model beverages of the various
      fruits. It was revealed that rotundone added at even subthreshold levels to model
      beverages did not confer directly the woody odor, but had significant effects on
      the overall flavors of the beverages, helping them to better approximate the
      natural flavors of the fruits.

PMID- 28516770
TI  - Conjugated Polymers Act Synergistically with Antibiotics to Combat Bacterial Drug
      Resistance.
AB  - The emergence of drug-resistant bacteria severely challenges the antimicrobial
      agents and antibacterial strategy. Here, we demonstrate a novel, simple, and
      highly efficient combination therapy strategy by direct combinations of cationic
      conjugated polymers (CCPs) with polypeptide antibiotics against Gram-negative and
      Gram-positive bacteria based on a synergistic antibacterial effect. The
      combination therapy method enhances the antibacterial efficacy with a
      significantly reduced antibiotic dosage. Also, the highly efficient and
      synergistic killing of drug-resistant bacteria is realized. Using combinations of
      CCPs and antibiotics to show increased antibacterial activity, this strategy will
      provide a much wider scope of the discovery of efficient antibacterial systems
      than that of antibiotic-antibiotic combinations. The proposed combination therapy
      method provides a universal and powerful platform for the treatment of pathogens,
      in particular, the drug-resistant bacteria, and also opens a new way for the
      development of efficient antibacterial systems.

PMID- 28516771
TI  - Highly Selective Cerebral ATP Assay Based on Micrometer Scale Ion Current
      Rectification at Polyimidazolium-Modified Micropipettes.
AB  - Development of new principles and methods for cerebral ATP assay is highly
      imperative not only for determining ATP dynamics in brain but also for
      understanding physiological and pathological processes related to ATP. Herein, we
      for the first time demonstrate that micrometer scale ion current rectification
      (MICR) at a polyimidazolium brush-modified micropipette can be used as the signal
      transduction output for the cerebral ATP assay with a high selectivity. The
      rationale for ATP assay is essentially based on the competitive binding ability
      between positively charged polyimidazolium and ATP toward negatively charged ATP
      aptamer. The method is well responsive to ATP with a good linearity within a
      concentration range from 5 nM to 100 nM, and high selectivity toward ATP. These
      properties essentially enable the method to determine the cerebral ATP by
      combining in vivo microdialysis. The basal dialysate level of ATP in rat brain
      cortex is determined to be 11.32 +/- 2.36 nM (n = 3). This study demonstrates
      that the MICR-based sensors could be potentially used for monitoring
      neurochemicals in cerebral systems.

PMID- 28516772
TI  - Synthesis of [2]Catenanes by Intramolecular Sonogashira-Type Reaction.
AB  - The catalytic activity of macrocyclic phenanthroline-CuI complexes was utilized
      to synthesize [2]catenanes by intramolecular Sonogashira-type reaction. The high
      reactivity of the acyclic starting material was critical to synthesize the
      [2]catenane in acceptable yields. The relationship between the yield of the
      [2]catenane and the structure of the starting materials was disclosed.

PMID- 28516775
TI  - Reagent Design and Ligand Evolution for the Development of a Mild Copper
      Catalyzed Hydroxylation Reaction.
AB  - Parallel synthesis and mass-directed purification of a modular ligand library,
      high-throughput experimentation, and rational ligand evolution have led to a
      novel copper catalyst for the synthesis of phenols with a traceless hydroxide
      surrogate. The mild reaction conditions reported here enable the late-stage
      synthesis of numerous complex, druglike phenols.

PMID- 28516774
TI  - Multiplexed MRM-Based Protein Quantitation Using Two Different Stable Isotope
      Labeled Peptide Isotopologues for Calibration.
AB  - When quantifying endogenous plasma proteins for fundamental and biomedical
      research - as well as for clinical applications - precise, reproducible, and
      robust assays are required. Targeted detection of peptides in a bottom-up
      strategy is the most common and precise mass spectrometry-based quantitation
      approach when combined with the use of stable isotope-labeled peptides. However,
      when measuring protein in plasma, the unknown endogenous levels prevent the
      implementation of the best calibration strategies, since no blank matrix is
      available. Consequently, several alternative calibration strategies are employed
      by different laboratories. In this study, these methods were compared to a new
      approach using two different stable isotope-labeled standard (SIS) peptide
      isotopologues for each endogenous peptide to be quantified, enabling an external
      calibration curve as well as the quality control samples to be prepared in pooled
      human plasma without interference from endogenous peptides. This strategy
      improves the analytical performance of the assay and enables the accuracy of the
      assay to be monitored, which can also facilitate method development and
      validation.

PMID- 28516776
TI  - Electrochemical Generation of Individual O2 Nanobubbles via H2O2 Oxidation.
AB  - Herein, we use Pt nanodisk electrodes (apparent radii from 4 to 80 nm) to
      investigate the nucleation of individual O2 nanobubbles generated by
      electrooxidation of hydrogen peroxide (H2O2). A single bubble reproducibly
      nucleates when the dissolved O2 concentration reaches ~0.17 M at the Pt electrode
      surface. This nucleation concentration is ~130 times higher than the equilibrium
      saturation concentration of O2 and is independent of electrode size. Moreover, in
      acidic H2O2 solutions (1 M HClO4), in addition to producing an O2 nanobubble
      through H2O2 oxidation at positive potentials, individual H2 nanobubbles can also
      be generated at negative potentials. Alternating generation of single O2 and H2
      bubbles within the same experiment allows direct comparison of the critical
      concentrations for nucleation of each nanobubble without knowing the precise
      size/geometry of the electrode or the exact viscosity/temperature of the
      solution.

PMID- 28516773
TI  - Amphiphilic BODIPY-Hydroporphyrin Energy Transfer Arrays with Broadly Tunable
      Absorption and Deep Red/Near-Infrared Emission in Aqueous Micelles.
AB  - BODIPY-hydroporphyrin energy transfer arrays allow for development of a family of
      fluorophores featuring a common excitation band at 500 nm, tunable excitation
      band in the deep red/near-infrared window, and tunable emission. Their biomedical
      applications are contingent upon retaining their optical properties in an aqueous
      environment. Amphiphilic arrays containing PEG-substituted BODIPY and chlorins or
      bacteriochlorins were prepared and their optical and fluorescence properties were
      determined in organic solvents and aqueous surfactants. The first series of
      arrays contains BODIPYs with PEG substituents attached to the boron, whereas in
      the second series, PEG substituents are attached to the aryl at the meso
      positions of BODIPY. For both series of arrays, excitation of BODIPY at 500 nm
      results in efficient energy transfer to and bright emission of hydroporphyrin in
      the deep-red (640-660 nm) or near-infrared (740-760 nm) spectral windows. In
      aqueous solution of nonionic surfactants (Triton X-100 and Tween 20) arrays from
      the second series exhibit significant quenching of fluorescence, whereas
      properties of arrays from the first series are comparable to those observed in
      polar organic solvents. Reported arrays possess large effective Stokes shift (115
      260 nm), multiple excitation wavelengths, and narrow, tunable deep-red/near-IR
      fluorescence in aqueous surfactants, and are promising candidates for a variety
      of biomedical-related applications.

PMID- 28516777
TI  - Improvements in Mass Spectrometry Assay Library Generation for Targeted
      Proteomics.
AB  - In data-independent acquisition mass spectrometry (DIA-MS), targeted extraction
      of peptide signals in silico using mass spectrometry assay libraries is a
      successful method for the identification and quantification of proteins. However,
      it remains unclear if high quality assay libraries with more accurate peptide ion
      coordinates can improve peptide target identification rates in DIA analysis. In
      this study, we systematically improved and evaluated the common algorithmic steps
      for assay library generation and demonstrate that increased assay quality results
      in substantially higher identification rates of peptide targets from mouse organ
      protein lysates measured by DIA-MS. The introduced changes are (1) a new spectrum
      interpretation algorithm, (2) reapplication of segmented retention time
      normalization, (3) a ppm fragment mass error matching threshold, (4) usage of
      internal peptide fragments, and (5) a multilevel false discovery rate
      calculation. Taken together, these changes yielded 14-36% more identified peptide
      targets at 1% assay false discovery rate and are implemented in three new open
      source tools, Fraggle, Tramler, and Franklin, available at
      https://github.com/fickludd/eviltools . The improved algorithms provide ways to
      better utilize discovery MS data, translating to substantially increased DIA
      performance and ultimately better foundations for drawing biological conclusions
      in DIA-based experiments.

PMID- 28516778
TI  - Surfactant Assemblies on Selected Nanostructured Surfaces: Evidence, Driving
      Forces, and Applications.
AB  - Surfactant adsorption at solid-liquid interfaces is critical for a number of
      applications of vast industrial interest and can also be used to seed surface
      modification processes. Many of the surfaces of interest are nanostructured, as
      they might present surface roughness at the molecular scale, chemical
      heterogeneity, as well as a combination of both surface roughness and chemical
      heterogeneity. These effects provide lateral confinement on the surfactant
      aggregates. It is of interest to quantify how much surfactant adsorbs on such
      nanostructured surfaces and how the surfactant aggregates vary as the degree of
      lateral confinement changes. This review focuses on experimental evidence on
      selected substrates, including gold- and carbon-based substrates, suggesting that
      lateral confinement can have pronounced effects both on the amount adsorbed and
      on the morphology of the aggregates as well as on a systematic study, via diverse
      simulation approaches, on the effect of lateral confinement on the structure of
      the surfactant aggregates. Atomistic and coarse-grained simulations conducted for
      surfactants on graphene sheets and carbon nanotubes are reviewed, as well as
      coarse-grained simulations for surfactant adsorption on nanostructured surfaces.
      Finally, we suggest a few possible extensions of these studies that could
      positively impact a few practical applications. In particular, the simultaneous
      effect of lateral confinement and of the coadsorption of molecular compounds
      within the surface aggregates is expected to yield interesting fundamental
      results with long-lasting consequences in applications ranging from drug delivery
      to the design of advanced materials.

PMID- 28516779
TI  - Synthesis of Cubic-Shaped Pt Particles with (100) Preferential Orientation by a
      Quick, One-Step and Clean Electrochemical Method.
AB  - A new approach has been developed for in situ preparing cubic-shaped Pt particles
      with (100) preferential orientation on the surface of the conductive support by
      using a quick, one-step, and clean electrochemical method with periodic square
      wave potential. The whole electrochemical deposition process is very quick (only
      6 min is required to produce cubic Pt particles), without the use of particular
      capping agents. The shape and the surface structure of deposited Pt particles can
      be controlled by the lower and upper potential limits of the square-wave
      potential. For a frequency of 5 Hz and an upper potential limit of 1.0 V (vs
      saturated calomel electrode), as the lower potential limit decreases to the H
      adsorption potential region, the Pt deposits are changed from nearly spherical
      particles to cubic-shaped (100)-oriented Pt particles. High-resolution
      transmission electron microscopy and selected-area electron diffraction reveal
      that the formed cubic Pt particles are single-crystalline and enclosed by (100)
      facets. Cubic Pt particles exhibit characteristic H adsorption/desorption peaks
      corresponding to the (100) preferential orientation. Ge irreversible adsorption
      indicates that the fraction of wide Pt(100) surface domains is 47.8%. The
      electrocatalytic activities of different Pt particles are investigated by ammonia
      electro-oxidation, which is particularly sensitive to the amount of Pt(100)
      sites, especially larger (100) domains. The specific activity of cubic Pt
      particles is 3.6 times as high as that of polycrystalline spherical Pt particles,
      again confirming the (100) preferential orientation of Pt cubes. The formation of
      cubic-shaped Pt particles is related with the preferential electrochemical
      deposition and dissolution processes of Pt, which are coupled with the periodic
      desorption and adsorption processes of O-containing species and H adatoms.

PMID- 28516780
TI  - Dual-Colored Carbon Dot Ratiometric Fluorescent Test Paper Based on a Specific
      Spectral Energy Transfer for Semiquantitative Assay of Copper Ions.
AB  - Classical pH test papers are widely used to measure the acid-base degree of media
      in a qualitative or semiquantitative manner. However, the extension of portable
      and inexpensive methods to a wide range of analytes so as to eliminate the
      tediousness of instrumental assays remains unsuccessful. Here, we report a novel
      kind of dual-colored carbon dot (CD) ratiometric fluorescent test paper for the
      semiquantitative assay of copper ions (Cu2+) by a dose-sensitive color evolution.
      The preparation of the test paper is based on the following two interesting
      findings: on the one hand, residual p-phenylenediamine at the surface of as
      synthesized red CDs (r-CDs) efficiently binds Cu2+ ions to produce a strong
      visible absorption that overlaps the emission of blue CDs (b-CDs); on the other
      hand, the Cu2+ ions render the adsorption of small b-CDs onto the surface of
      larger r-CDs through their dual-coordinating interactions with the surface
      ligands of both r-CDs and b-CDs. These two mechanisms lead to a specific spectral
      energy transfer to quench the fluorescence of b-CDs with a sensitive detection
      limit of 8.82 nM Cu2+, whereas the red fluorescence of r-CDs is unaffected as a
      stable internal standard. Ratiometric fluorescent test papers have been prepared
      using a mixture of r-CDs and b-CDs (1:7) as ink by jetprinting on a piece of
      paper. With the addition of Cu2+ ions, the blue test paper produces a consecutive
      wide-colored evolution from blue to orange-red, with a dose-discerning ability as
      low as 25 nM.

PMID- 28516781
TI  - Patterns, Variability, and Predictors of Urinary Triclosan Concentrations during
      Pregnancy and Childhood.
AB  - Exposure to triclosan, an antimicrobial used in many consumer products, is
      ubiquitous in the United States, yet only limited data are available on the
      predictors and variability of exposure, particularly in children. We examined the
      patterns, variability, and predictors of urinary triclosan concentrations in 389
      mother-child pairs enrolled in the Health Outcomes and Measures of the
      Environment Study from 2003 to 2006. We quantified triclosan in 3 urine samples
      collected from women between 16 weeks of pregnancy and birth and 6 urine samples
      collected from children between the ages of 1-8 years. For maternal and child
      samples, we calculated intraclass correlation coefficients (ICCs) to assess
      triclosan reproducibility and identified sociodemographic predictors of
      triclosan. Among 8 year old children, we examined associations between triclosan
      and personal-care product use. We detected triclosan in >70% of urine samples.
      Median maternal triclosan varied across pregnancy from 17 to 11 ng/mL, while in
      children, median concentrations increased from 3.6 to 17 ng/mL over the first 4
      years of life, declining slightly at later ages. Triclosan reproducibility was
      fair to good during pregnancy and for child samples taken weeks apart (ICCs = 0.4
      0.6) but poor for annual child samples (ICCs = 0.2-0.4). Triclosan was 66% (95%
      CI: 29-113) higher in 8 year olds using hand soap compared to nonusers and
      increased monotonically with hand-washing frequency. Toothpaste use in children
      was also positively associated with triclosan. Our results suggest that urinary
      triclosan concentrations have modest stability over weeks to months; children are
      exposed to triclosan through the use of some personal-care products.

PMID- 28516785
TI  - Measurement of intact parathormone during operation for primary
      hyperparathyroidism.
AB  - In this prospective study, the role of the intact parathormone (iPHT) levels for
      the verification of pathologic parathyroid tissue removal during
      parathyroidectomy, was analyzed in 441 patients diagnosed with primary
      hyperparathyroidism. The level of intact parathormone was obtained before the
      initial incision (baseline level) and 10 minutes after the pathologic parathyroid
      gland removal (control value). In 80 % of cases, the decrease of intact
      parathormone was more than 50 % of the baseline level. The comparison of
      preoperative and postoperative intact parathormone levels can also be used as
      marker of parathyroid hyperplasia or persistent hyperparathyroidism. This method
      is necessary mainly for performance of focused, miniinvasive approaches as well
      as in reoperations. This method is of significant benefit in cases of negative
      preoperative examination methods. The determination of intact parathormone level
      increases the success of parathyroidectomy (Ref. 26).

PMID- 28516786
TI  - Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical
      characteristic in women with unexplained recurrent miscarriage.
AB  - INTRODUCTION: Recurrent miscarriage (RM) defined as 2 or more spontaneous
      miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying
      to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains
      unexplained. Reduced expression of Angiogenic factors such as: vascular
      endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous
      miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND
      OBJECTIVES: To investigate the relationships between serum level of VEGF-A and
      VEGF-C with clinical characteristic in women with URM and compare to pregnant and
      healthy women. MATERIALS AND METHODS: A case-control study, which was conducted
      between 90 non-pregnant women with history of RM, age-matched with 70 non
      pregnant women without history of recurrent abortion with at least one child
      (controls) and 70 pregnant women without history of recurrent abortion with at
      least one child (controls). Those with unexplained RM were eligible. Demographic
      and Anthropometric data were retrieved by pre-test questionnaire and serum level
      of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that
      maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87+/-88.1
      vs 238.8+/-99.6) compared to healthy (239.1+/-99.7 vs 275.5+/-133.08) and
      pregnant (301.5+/-76.4 vs 402.5+/-128.6) women as control groups. Univariate
      analysis demonstrated that clinical characteristic factors were significantly
      associated with concentration of VEGF-A and VEGF-C in cases and controls.
      CONCLUSIONS: Our findings suggest that these molecules could be used as potential
      predictive markers of miscarriage in these women presenting with URM (Tab. 4,
      Fig. 5, Ref. 40).

PMID- 28516782
TI  - Exploring Site-Specific N-Glycosylation of HEK293 and Plant-Produced Human IgA
      Isotypes.
AB  - The full potential of recombinant Immunoglobulin A as therapeutic antibody is not
      fully explored, owing to the fact that structure-function relationships of these
      extensively glycosylated proteins are not well understood. Here monomeric IgA1,
      IgA2m(1), and IgA2m(2) variants of the anti-HER2 antibody (IgG1) trastuzumab were
      expressed in glyco-engineered Nicotiana benthamiana plants and in human HEK293-6E
      cells. All three IgA isotypes were purified and subjected to biophysical and
      biochemical characterization. While no differences in assembly, antigen binding,
      and glycosylation occupancy were observed, both systems vary tremendously in
      terms of glycan structures and heterogeneity of glycosylation. Mass-spectrometric
      analysis of site-specific glycosylation revealed that plant-produced IgAs carry
      mainly complex-type biantennary N-glycans. HEK293-6E-produced IgAs, on the
      contrary, showed very heterogeneous N-glycans with high levels of sialylation,
      core-fucose, and the presence of branched structures. The site-specific analysis
      revealed major differences between the individual N-glycosylation sites of each
      IgA subtype. Moreover, the proline-rich hinge region from HEK293-6E cell-derived
      IgA1 was occupied with mucin-type O-glycans, whereas IgA1 from N. benthamiana
      displayed numerous plant-specific modifications. Interestingly, a shift in
      unfolding of the CH2 domain of plant-produced IgA toward lower temperatures can
      be observed with differential scanning calorimetry, suggesting that distinct
      glycoforms affect the thermal stability of IgAs.

PMID- 28516783
TI  - Antidiabetic Disruptors of the Glucokinase-Glucokinase Regulatory Protein Complex
      Reorganize a Coulombic Interface.
AB  - The glucokinase regulatory protein (GKRP) plays an essential role in glucose
      homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and
      triggering its localization to the hepatocyte nucleus upon glucose deprivation.
      Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote
      assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized
      piperazines with potent in vivo antidiabetic activity disrupt the complex. Here,
      we establish the molecular basis by which these natural and synthetic ligands
      modulate the GCK-GKRP interaction. We demonstrate that a small-molecule disruptor
      of the protein-protein interaction utilizes a two-step conformational selection
      mechanism to associate with a rare GKRP conformation constituting 3% of the total
      population. Conformational heterogeneity of GKRP is localized to the N-terminus
      and deleting this region eliminates the ability of sorbitol 6-phosphate to
      promote the GCK-GKRP interaction. Stabilizing ligands favor an extended N
      terminus, which sterically positions two arginine residues for optimal Coulombic
      interaction with a pair of carboxylate side chains from GCK. Conversely,
      disruptors promote a more compact N-terminus in which an interfacial arginine
      residue is stabilized in an unproductive orientation through a cation-pi
      interaction with tyrosine 75. Eliminating the ability to sample this binding
      impaired conformation enhances the intrinsic inhibitory activity of GKRP.
      Elucidating the molecular basis of ligand-mediated control over the GCK-GKRP
      interaction is expected to impact the development and future refinement of
      therapeutic agents for diabetes and cardiovascular disease, which result from
      improper GKRP regulation of GCK.

PMID- 28516787
TI  - Antiproliferative effect of a food coloring on colon cancer cell line.
AB  - 4-MEI (4-Methylimidazole) is used as a chemical intermediate, crude material or
      component in the manufacture of pharmaceuticals, photographic and
      photothermographic chemicals, dyes and pigments and agricultural chemicals. 4-MEI
      is unintentionally found in our food. Caramel colour (which is the most used
      beverage colouring and food), dark beers and common brands of cola drinks may
      comprise more than 100 MUg of this compound per 12-ounce serving. 4-MEI is widely
      used by people and colon cancer is common in our countries. So, it was decided to
      do in vitro analysis of anti-cancer effect of 4-MEI by MTT test using htc-116
      cell line.In this study, mouse Htc-116 cell line was treated with 4-MEI
      concentrations of 300, 450, 600 and 750 ug/mL for 24 hours and 48 hours periods,
      after that antiproliferative effect of the 4-MEI was studied by MTT assay. In
      this study 4-MEI at highest concentration of 24h and at all concentration for 48
      h treatment time significantly inhibited cell proliferation when it was compared
      to control. Also, exposing to the 4-MEI for 48 hours led to a decrease in cells
      proliferation by concentration dependent manner. This result showed that 4-MEI
      had anticancer effect in htc-116 cells. However, it has to be evaluated with
      different new studies (Tab. 1, Fig. 4, Ref. 19).

PMID- 28516784
TI  - In-Culture Cross-Linking of Bacterial Cells Reveals Large-Scale Dynamic Protein
      Protein Interactions at the Peptide Level.
AB  - Identification of dynamic protein-protein interactions at the peptide level on a
      proteomic scale is a challenging approach that is still in its infancy. We have
      developed a system to cross-link cells directly in culture with the special
      lysine cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). We used the
      Gram-positive model bacterium Bacillus subtilis as an exemplar system. Within 5
      min extensive intracellular cross-linking was detected, while intracellular cross
      linking in a Gram-negative species, Escherichia coli, was still undetectable
      after 30 min, in agreement with the low permeability in this organism for
      lipophilic compounds like BAMG. We were able to identify 82 unique interprotein
      cross-linked peptides with <1% false discovery rate by mass spectrometry and
      genome-wide database searching. Nearly 60% of the interprotein cross-links occur
      in assemblies involved in transcription and translation. Several of these
      interactions are new, and we identified a binding site between the delta and
      beta' subunit of RNA polymerase close to the downstream DNA channel, providing a
      clue into how delta might regulate promoter selectivity and promote RNA
      polymerase recycling. Our methodology opens new avenues to investigate the
      functional dynamic organization of complex protein assemblies involved in
      bacterial growth. Data are available via ProteomeXchange with identifier
      PXD006287.

PMID- 28516788
TI  - Anti-oxidative effect of resveratrol on aluminum induced toxicity in rat cerebral
      tissue.
AB  - INTRODUCTION: The direct protective effects of resveratrol against oxidative
      stress have been demonstrated in neuroglial cells, the mechanisms of these
      effects are not fully understood. The aim of this research was to study the
      effect of resveratrol on AL induced cerebral injury in rat. METHODS: We divided
      the groups as follows with 10 animals each: a) Group I - served as control
      receiving normal drinking water and diet ad libitum. b) Group II - animals were
      administered aluminum at a dose level of 100 mg/kg body weight for a period of 6
      weeks daily through oral gavage. c) Group III - animals were administered
      aluminum at a dose level of 100 mg/kg body weight and resveratrol at a dose of 10
      mg/kg body weight intraperitoneally for a period of 6 weeks daily. After 6 weeks
      rats were anesthetized and decapitated. Brains were removed immediately and
      frozen in liquid nitrogenRESULTS: The levels of SOD and GPx antioxidant enzymes
      were decreased in all of the groups receiving aluminium, but it was less severe
      in resveratrol treated group. SOD and GPx levels in aluminium + resveratrol group
      were higher than in the aluminum group (p < 0.05). MDA level, as an index of
      lipid peroxidation, increased significantly in all of the groups receiving
      aluminium. MDA level was lower in aluminium + resveratrol group compared to
      aluminum group and the difference was significant (p < 0.05). CONCLUSIONS: This
      study suggests that resveratrol is effective in preventing AL induced toxicity by
      reducing MDA production in cerebral tissue. Resveratrol also attenuated SOD and
      GPx suppression in cerebral tissue significantly. Our findings provide the
      rationale for further studies directed to understanding the mechanism of
      resveratrol in preventing neurodeterioration (Tab. 1, Ref. 35).

PMID- 28516789
TI  - Protective effect of pravastatin on doxorubicin-induced hepatotoxicity.
AB  - OBJECTIVE: The present study was designed to investigate the possible protection
      of pravastatin against hepatic oxidative stress and dysfunctions induced by
      doxorubicin in rats. BACKGROUND: Statins have beneficial effects on oxidative
      stress and inflammation. METHODS: Male Sprague-Dawley rats were divided into four
      groups. Control group (received saline orally), Group 2 received pravastatin (20
      mg/kg, i.p. for 15 days), Group 3 received single dose doxorubicin (15 mg/kg,
      i.p.), Group 4 was treated with pravastatin (20 mg/kg, i.p.) daily from 5 days
      before to 10 days after injection of doxorubicin (15 mg/kg, i.p.). Hepatic
      toxicity was estimated by biochemical parameters and oxidative stress and
      histopathological studies. RESULTS: Administration of doxorubicin indicated an
      increase in ALT, AST, ALP, TG, cholesterol, LDL and total bilirubin levels (p <
      0.01). Doxorubicin caused a reduction in HDL and albumin levels (p < 0.01) as
      well as superoxide dismutase, glutathione peroxidase and catalase activities (p <
      0.05) with a concomitant increase in liver malondialdehyde (p < 0.05) and liver
      damage (p < 0.001). Pravastatin reduced the scale liver injury (p < 0.001) and
      protected liver functions and other biochemical parameters (p < 0.01). Increase
      in malondialdehyde level associated with a reduction in antioxidant activities in
      the doxorubicin group was attenuated by pravastatin treatment (p < 0.05).
      CONCLUSION: Results indicated that pravastatin has a protective effect on the
      liver against doxorubicin-induced hepatotoxicity in rats (Tab. 3, Fig. 2, Ref.
      34).

PMID- 28516790
TI  - Oxidative effects of extremely low frequency magnetic field and radio frequency
      radiation on testes tissues of diabetic and healthy rats.
AB  - With the development of technology, people are increasingly under the exposure of
      electromagnetic fields. Individuals with chronic diseases such as diabetes are
      now long-term exposed to Radio Frequency-RF radiation and extremely low frequency
      (ELF) magnetic fields (MFs). The purpose of this present study is to investigate
      oxidative effects and antioxidant parameters of ELF MFs and RF radiation on
      testis tissue in diabetic and healthy rats. Wistar male rats were divided into 10
      groups. Intraperitoneal single dose STZ (65 mg/kg) dissolved in citrate buffer
      (0.1M (pH 4.5)) was injected to diabetes groups. ELF MFs and RF radiation were
      used as an electromagnetic exposure for 20 min/day, 5 days/week for one month.
      Testis tissue oxidant malondialdehyde (MDA), and antioxidants glutathione (GSH),
      and total nitric oxide (NOx) levels were determined. The results of ANOVA and
      Mann-Whitney tests were compared; p < 0.05 was considered significant. ELF and RF
      radiation resulted in an increase in testicular tissue MDA and NOX levels (p <
      0.05), and caused a decrease in GSH levels (p < 0.05) in both healthy and
      diabetic rats, yet more distinctively in diabetic rats. The most pronounced
      effect was recorded in D-RF + ELF group (p < 0.005). Both radiation practices
      increased the oxidative stress in testis tissue while causing a decrease in
      antioxidant level which was more distinctive in diabetic rats (Tab. 1, Fig. 3,
      Ref. 30).

PMID- 28516791
TI  - Which one is more effective for the treatment of rat sepsis model: thalidomide or
      etanercept?
AB  - OBJECTIVE: We aimed to investigate the protective effect of selected treatment
      agents on liver injury in lipopolysaccharide (LPS)-induced rat sepsis model.
      BACKGROUND: The sepsis includes complex inflammatory responses between a
      microbial pathogen and the host immune system, and leads to organ failure and
      also death. METHODS: This study was performed with 29 male Wistar Albino rats.
      Rats were divided randomly into five groups: Sham group, LPS-treated sepsis
      group, LPS+thalidomide treated group, LPS+etanercept treated group and
      LPS+thalidomide+etanercept treated group, respectively. Liver tissue tumor
      necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and interleukin 6
      (IL-6) levels were determined by enzyme-linked immuno-sorbent assay (ELISA)
      method. The expression of nuclear factor kappa-light-chain-enhancer of activated
      B cells (NF-kappaB) was performed using western blot analysis. RESULTS: The
      levels of tissue TNF-alpha, IL-1beta and IL-6 were found statistically
      significantly higher in sepsis group than in the sham group. TNF-alpha levels
      were found statistically significantly decreased in LPS+etanercept and
      LPS+thalidomide+etanercept treated groups when compared with LPS group (p <
      0.05). For IL-1beta and IL-6 levels a statistically significant decline was
      observed in the LPS+thalidomide and LPS+etanercept treated groups compared to the
      LPS group (p < 0.05). Expression of NF-kappaB protein in liver tissue was
      significantly elevated in the LPS group compared to sham group (p < 0.001). In
      treatment groups, a marked decrease was observed in NF-kappaB protein expression.
      CONLUSION: The results of this investigation suggested that etanercept and
      thalidomide administration may have a beneficial effect on LPS-induced sepsis.
      So, the present study may have significant clinical relevance, but clinical
      trials are needed to confirm these results (Tab. 1, Fig. 1, Ref. 36).

PMID- 28516792
TI  - Apoptosis of colon cancer cells under the effect of geldanamycin derivate.
AB  - AIM: The apoptotic effect of geldanamycin derivative may be important for the
      colorectal cancer therapy. The mechanisms of apoptosis require understanding of
      the behavior of colon cancer cell line Colo-205 which mimics colon
      adenocarcinoma. Therefore, the effect of IC50 dose of 17-allylamino-17
      demethoxygeldanamycin (17-AAG) on the colon cancer cells in vitro was studied for
      its anti-apoptotic activity. METHOD: Apoptotic ratio of the Colo-205 cells was
      determined after 17-AAG application with terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL) staining and apoptosis related genes. Apoptosis
      signal path related key mitochondrial proteins, cytochrome c, bcl-2, caspase 9
      and Apaf-1 expression were examined with RT-PCR method. RESULTS: 17-AAG caused
      induction of cell death. Apoptotic related genes such as cytochrome-c, Apaf-1 and
      caspase-9 protein expressions were increased significantly (p < 0.05) and anti
      apoptotic bcl-2 expression was decreased significantly (p < 0.05). Our results
      indicated that the application of 17-AAG on Colo-205 cells showed anticancer
      effect by the apoptosis due to alteration of apoptotic genes. CONCLUSION: The
      apoptotic effect of 17-AAG as an natural product for alternative medicine would
      be very important for the success and quality of life during the treatment of
      colon carcinoma with the combination of anticancer drugs (Tab. 1, Fig. 2, Ref.
      32).

PMID- 28516793
TI  - Red or white wine consumption effect on atherosclerosis in healthy individuals
      (In Vino Veritas study).
AB  - AIMS: Consumption of wine has a protective effect on cardiovascular diseases.
      Data from prospective, long-term, head-to-head comparisons of effects of
      different drinks on markers of atherosclerosis have been insufficient. METHODS
      AND RESULTS: In Vino Veritas (IVV) study is long-term, prospective, multi-centre,
      randomized trial comparing effects of red and white wine on atherosclerosis. 157
      healthy subjects were randomized to white or red wine consumption for one year.
      We did not find increase in HDL-cholesterol in the whole group (1.66+/-0.58 vs
      1.62+/-0.49, p=0.180) or difference between both groups (1.60+/-0.53 vs 1.64+/
      0.46, p=0.634). At 12 months there was reduction of LDL-cholesterol in both
      groups, but with no difference between the groups (3.37+/-0.75 vs 3.60+/-1.10,
      p=0.134); there was no difference between the groups in total cholesterol, CRP,
      fasting blood glucose and liver function tests. Both groups had comparable
      differences from baseline in levels of parameters of oxidative stress.
      CONCLUSION: We did not find any clinically relevant differences in the lipid
      profile, CRP, fasting blood glucose and other markers of atherosclerosis, between
      long-term consumption of red and white wine. Moreover, we were unable to confirm
      the hypothesis that wine drinking is associated with an elevation of HDL (Tab. 7,
      Fig. 1, Ref. 30).

PMID- 28516794
TI  - Association of the postoperative white blood cells (WBC) count in peripheral
      blood after radical surgical treatment of left upper lobe non-small cell lung
      cancer (NSCLC) with overall survival - single center results.
AB  - INTRODUCTION: The individual patient prognosis after radical surgery for Non
      small cell lung cancer (NSCLC) of left upper lobe remains still unclear. The
      purpose of this study is to evaluate the predictive value of elevated white blood
      cell count in peripheral blood as early indicator of postoperative NSCLC
      prognosis. METHODS: A retrospective statistical analysis was performed studying
      patients subject to radical treatment of left upper lobe NSCLC in period of five
      years with subsequent one to three-year monitoring of morbidity and mortality of
      the patient population. The statistical ROC (Receiver Operating Characteristic)
      analysis of the WBC count in peripheral blood third day after the operation was
      used to evaluate the relationship with overall survival, with respect to patients
      surviving for at least 24 months. RESULTS: Based on the results of the ROC
      analysis with a total area under the curve (AUC) of 0.67, it is possible to
      confirm that the WBC count established third day after the operation allows us to
      classify patients into groups according to the 24-month overall survival.
      CONCLUSION: Our findings confirm the potential of using WBC count to improve
      current protocols to establish postoperative prognosis for NSCLC of the upper
      left lobe (Tab. 2, Fig. 1, Ref. 11).

PMID- 28516795
TI  - A comprehensive guide to telocytes and their great potential in cardiovascular
      system.
AB  - Telocytes, a recently discovered type of interstitial cells, have a very
      distinctive morphology - the small cell body with long extensions, named
      telopodes. In our review, apart from introducing general aspects of telocytes, we
      focus on properties, functions and future potential of those cells in
      cardiovascular system. However, physiological functions of telocytes in
      cardiovascular system are still regarded as quite enigmatic. Previous studies
      claim that they play a role in organogenesis and regeneration, bioelectrical
      signalling, mechanoelectrical coupling, anti-oxidative protection, angiogenesis
      and regulation of blood flow. As well, they are presumably connected with the
      presence of blood-myocardium barrier and proper organisation of extracellular
      matrix. Moreover, there exists a significant link between the quantity of
      telocytes in tissue and numerous cardiovascular diseases such as: myocardial
      infarction, cardiomyopathies, systemic sclerosis, heart failure, atrial
      fibrillation, isolated atrial amyloidosis, myxomatous valve degeneration and
      hyperplastic consequences of vascular injury. Thanks to their unique properties,
      telocytes might be a breakthrough in treatment of cardiovascular diseases, as
      they may be effective in reversing effects of myocardial infarction. Telocytes
      also may play a major role in tissue engineering - they might be the key factor
      in creating stable and efficient vascular network in larger synthetic tissues or
      organs (Tab. 1, Fig. 3, Ref. 53).

PMID- 28516796
TI  - Legionella spp. in dental unit waterlines.
AB  - OBJECTIVE: To determine the current presence of Legionella spp. in the output
      water of dental unit waterlines (DUWLs) and examine its mitigation by
      disinfection at the Institute of Dentistry and Oral Sciences, Faculty of Medicine
      and Dentistry, Palacky University Olomouc and University Hospital Olomouc.
      MATERIAL AND METHODS: The first stage of our survey involved collecting samples
      of DUWL output water from 50 dental chair units (DCUs), and 2 samples of the
      incoming potable water. In October 2015, a one-time disinfection (1 % Stabimed)
      of DUWLs was conducted. This was followed by collecting 10 control samples
      (survey stage 2). RESULTS: From the total of 50 samples (survey stage 1), 18
      samples (36.0 %) tested positive for Legionella spp. Following the disinfection,
      nine of the ten samples no longer showed any presence of Legionella. CONCLUSION:
      Based on culture results, the one-time disinfection (1 % Stabimed) was effective.
      We are unable to comment on the duration of positive effect of disinfection on
      the occurrence of Legionella spp. in the outlet water. It was a one-time survey
      (Tab. 2, Ref. 32).

PMID- 28516798
TI  - Complementary and Alternative Medicine Use in Uninsured Children in Texas.
AB  - Use of complementary and alternative medicine (CAM) among US children is 12%
      according to the 2012 National Health Interview Study. Certain pediatric
      populations have higher CAM use. We studied an uninsured population because
      limited access to care likely results in higher CAM use. We surveyed 250
      uninsured patients in a free pediatric mobile clinic program. In the largely
      Hispanic population, rate of CAM use in the preceding 12 months was 45% among
      children and 59% among parents. Ninety-one percent of children who used CAM had
      parents who used CAM while only 32% of parents used CAM for themselves but did
      not use CAM for their children ( P < .001). Seven parents (3%) and 4 children
      (2%) had ever discussed their CAM use with a physician. Since CAM use is
      significant in this uninsured population and families do not generally discuss
      CAM with physicians, health care providers must ask about CAM use and provide
      guidance.

PMID- 28516797
TI  - Blood glucose and insulin and correlation of SLC25A13 mutations with biochemical
      changes in NICCD patients.
AB  - Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a
      hereditary metabolic disease arising from biallelic mutations of SLC25A13. This
      study aimed to explore the characteristics of fasting blood glucose (FBG),
      fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their
      SLC25A13 genetic mutations and further discuss the correlation between SLC25A13
      genetic mutations and biochemical changes. Seventy-two cases of infants with
      cholestasis disease were gathered. Among them, 36 cases with NICCD diagnosis were
      case group. Meanwhile, 36 cases with unknown etiology but excluded NICCD were
      control group. FBG, FINS, C-P, ALT, AST, GGT, ALP, TG, HDL-C, LDL-C and Non-HDL-C
      were collected from all subjects, and DNA was extracted from venous blood for
      SLC25A13 mutations detection. The incidence of hypoglycemia was 3% in NICCD
      group. There were no significant statistical difference of FBG, FINS and C-P
      between NICCD and INC groups ( P > 0.05). ALT, LDL-C and Non-HDL-C levels in
      NICCD group were lower than the INC group, while SLC25A13 mutations were
      associated with the level of GGT ( P < 0.05). Ten different SLC25A13 genetic
      mutations were detected, among which, 851del4, IVS16ins3kb, IVS6+5 G > A and
      1638ins23 mutations made up 82% of all mutations. The incidence of hypoglycemia
      may be higher in small gestational age infants with NICCD. Low LDL-C may be one
      of the characteristics of dyslipidemia in NICCD infants. There was a correlation
      between SLC25A13 gene mutations distribution and the GGT level, but the meaning
      of this finding remains to be further in-depth study. Impact statement This study
      aims to compare FBG, FINS, C-P, other biochemical and clinical manifestations
      between NICCD and non-NICCD infants, and discuss differential diagnosis of NICCD
      and INC beyond the genetic analysis. And investigate the correlation between
      SLC25A13 genetic mutations and biochemical changes. This work presented that
      incidence of hypoglycemia may be higher in small gestational age infants with
      NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD
      infants. There was a correlation between SLC25A13 gene mutations distribution and
      the GGT level.

PMID- 28516800
TI  - Undertriage of Pediatric Major Trauma Patients in the United States.
AB  - Although trauma undertriage has been widely discussed in the literature,
      undertriage in the pediatric trauma population remains understudied. Using the
      2009-2013 Nationwide Emergency Department Sample, we assessed the national
      undertriage rate in pediatric major trauma patients (age <=16 years and injury
      severity score [ISS] >15), and identified factors associated with pediatric
      trauma undertriage. Nationally, 21.7% of pediatric major trauma patients were
      undertriaged. Children living in rural areas were more likely to be undertriaged
      ( P = .02), as were those without insurance ( P = .00). Children with life
      threatening injuries were less likely to be undertriaged ( P < .0001), as were
      those with chronic conditions ( P < .0001). Improving access to specialized
      pediatric trauma care through innovative service delivery models may reduce
      undertriage and improve outcomes for pediatric major trauma patients.

PMID- 28516801
TI  - Representations of mental health and arts participation in the national and local
      British press, 2007-2015.
AB  - We analysed news articles published in national and local British newspapers
      between 2007 and 2015 to understand (1) how mental health and arts participation
      were framed and (2) how the relationships between participants in arts
      initiatives were conceptualised. Using corpus-assisted qualitative frame
      analysis, we identified frames of recovery, stigma and economy. The recovery
      frame, which emphasised that mental illness can be treated similarly to physical
      illness, positioned arts participation as a form of therapy that can complement
      or substitute medication. The stigma frame presented arts participation as a
      mechanism for challenging social conceptions that mentally ill individuals are
      incapable of productive work. The economy frame discussed the economic burden of
      mentally ill individuals and portrayed arts participation as facilitating their
      return to employment. Using thematic analysis, which paid attention to the
      representation of social actors, we found that service users were identified as
      the prime beneficiaries of arts initiatives, and arts participation was
      conceptualised as a way to bring people with mental health issues together. We
      discuss these findings against existing research on media representations of
      mental health and the concept of 'mutual recovery' and suggest what wider
      concurrent developments in the areas of mental health and the media may account
      for the uncovered frames and themes.

PMID- 28516799
TI  - Oral Health Promotion During Well Visits.
AB  - Training pediatric residents in Bright Futures and oral health concepts is
      critical to improving oral health. This study's objective was to determine the
      skill level of pediatric residents in integrating oral health promotion during
      health supervision visits of 12- to 35-month-old children. One hundred forty
      three pediatric residents participated in an evaluation of the effectiveness of a
      Bright Futures oral health curriculum. Competencies assessed preintervention
      included partnership building, communication, and integration of oral health
      concepts. Pediatric residents' abilities to integrate oral health promotion into
      health supervision visits varied considerably. Residents demonstrated greater
      skill in communication and partnership building compared with oral health
      promotion behaviors and performance of an oral examination. Further education is
      needed at a national level if we are to meet Healthy People 2020 goals.

PMID- 28516802
TI  - The Influence of Heating on Toe pressure in Patients with Peripheral Arterial
      Disease.
AB  - BACKGROUND AND AIM: The toe skin temperature in vascular patients can be low,
      making reliable toe pressure measurements difficult to obtain. The aim of this
      study was to evaluate the effect of heating on the toe pressure measurements.
      MATERIALS AND METHODS: A total of 86 legs were examined. Brachial pressure and
      toe pressure were measured at rest in a supine position using a laser Doppler
      device that also measured skin temperature. After heating the toes for 5 min with
      a heating pad, we re-measured the toe pressure. Furthermore, after heating the
      skin to 40 degrees  with the probe, toe pressures were measured a third time.
      RESULTS: The mean toe skin temperature at the baseline measurement was 24.0 
      degrees C (standard deviation: 2.8). After heating the toes for 5 min with a warm
      heating pad, the skin temperature rose to a mean 27.8  degrees C (standard
      deviation: 2.8; p = 0.000). The mean toe pressure rose from 58.5 (standard
      deviation: 32) to 62 (standard deviation: 32) mmHg (p = 0.029). Furthermore,
      after the skin was heated up to 40  degrees C with the probe, the mean toe
      pressure in the third measurement was 71 (standard deviation: 34) mmHg (p =
      0.000). The response to the heating varied greatly between the patients after the
      first heating-from -34 mmHg (toe pressure decreased from 74 to 40 mmHg) to +91
      mmHg. When the toes were heated to 40  degrees C, the change in to toe pressure
      from the baseline varied between -28 and +103 mmHg. CONCLUSION: Our data indicate
      that there is a different response to the heating in different clinical
      situations and in patients with a different comorbidity.

PMID- 28516803
TI  - Differentials in Cardiovascular Risk Factors and Diabetes by Socioeconomic Status
      and Sex in Kalutara, Sri Lanka.
AB  - Since 1950, cardiovascular disease (CVD) has emerged as a leading cause of
      mortality in Sri Lanka, especially in men. In 2014, a survey in Kalutara to
      assess CVD and type 2 diabetes mellitus (T2DM) risk factors in adults aged 25 to
      64 years (n = 1011), and associations with sex and socioeconomic status (SES),
      found similar CVD risk factors in both sexes, except for daily tobacco smoking at
      19% in men and nil in women, and higher body mass index (BMI) in women than men.
      With increasing SES in men, there were significant linear increases in mean BMI,
      waist circumference, mean systolic and diastolic blood pressure, mean fasting
      plasma glucose, and T2DM prevalence, but decreases in tobacco smoking. Whereas in
      women higher SES was associated with a significant increase in mean BMI, but a
      significant decrease in hypertension prevalence. Tobacco smoking is the main risk
      factor explaining higher CVD mortality in men compared with women.

PMID- 28516804
TI  - Spinal cord atrophy as a primary outcome measure in phase II trials of
      progressive multiple sclerosis.
AB  - OBJECTIVES: To measure the development of spinal cord (SC) atrophy over 1 year in
      patients with progressive multiple sclerosis (PMS) and determine the sample sizes
      required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA)
      as an outcome measure in clinical trials. METHODS: In total, 44 PMS patients (26
      primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple
      sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12
      months. SC-CSA was measured using the three-dimensional (3D) fast field echo
      sequences acquired at 3T and the active surface model. Multiple linear
      regressions were used to investigate changes in imaging measurements. RESULTS:
      PPMS patients had shorter disease duration, lower Expanded Disability Status
      Scale (EDSS) and larger SC-CSA than SPMS patients. All patients together showed a
      significantly greater decrease in percentage SC-CSA change than HCs, which was
      driven by the PPMS. All patients deteriorated over 1 year, but no association was
      found between percentage SC-CSA change and clinical changes. The sample size per
      arm required to detect a 50% treatment effect over 1 year, at 80% power, was 57
      for PPMS and 546 for SPMS. CONCLUSION: SC-CSA may become an outcome measure in
      trials of PPMS patients, when they are at an early stage of the disease, have
      moderate disability and modest SC atrophy.

PMID- 28516805
TI  - Mesial temporal lobe and subcortical grey matter volumes differentially predict
      memory across stages of multiple sclerosis.
AB  - BACKGROUND/OBJECTIVE: Memory deficits due to multiple sclerosis (MS) have been
      variably linked to lower subcortical grey matter (SCGM) and mesial temporal lobe
      (MTL) volumes. We investigated which is the better predictor and whether this
      changes across disease stages. METHODS/RESULTS: Memory was assessed in 315
      patients. Magnetic resonance imaging (MRI) measured volumes of total brain, grey
      matter, white matter, MTL (hippocampus, amygdala) and SCGM (thalamus, caudate).
      MTL predicted memory in the total sample and in patients with earlier (<10 years)
      or later (?10 years) relapsing disease. SCGM (specifically thalamus) predicted
      memory in progressive patients. CONCLUSIONS: Neuroanatomical correlates of memory
      deficits differ across disease stages.

PMID- 28516806
TI  - Is bisphenol A exposure associated with the development of glucose intolerance
      and increased insulin resistance in Thais?
AB  - Bisphenol A (BPA), the monomeric component of polycarbonate plastics, reportedly
      possesses endocrine-disrupting effects. Exposure to low levels of BPA during more
      vulnerable periods leads to abnormalities related to sexual development in
      experimental animals. Moreover, recently a few epidemiological studies in
      Caucasians have demonstrated the association of BPA exposure with type 2
      diabetes. Therefore, in the present study we examined the association of BPA
      exposure and abnormal glucose tolerance in Thais. This is a cross-sectional study
      of 240 participants aged at least 50 years, randomly selected by computer
      generated random numbers within each glucose tolerance status from an oral
      glucose tolerance study of 661 participants. There were 80 participants in each
      group of type 2 diabetes, impaired glucose tolerance (IGT) and normal glucose
      tolerance (NGT). Serum BPA was measured by competitive ELISA. The detection rate
      of BPA was significantly higher in participants with IGT compared to those with
      NGT ( p < 0.05), while no difference was found between participants with type 2
      diabetes and NGT. When participants with type 2 diabetes were stratified into
      those with fasting plasma glucose (FPG) under the diabetic threshold (<126 mg/dL)
      and those over (>=126 mg/dL), it was found that those with FPG under the diabetic
      threshold had measurable rates of BPA comparable to those with IGT, and rates
      significantly higher than the NGT group ( p < 0.05), while those with FPG over
      the diabetic threshold did not have higher rates of measurable BPA compared with
      the NGT group. In conclusion, BPA exposure is not uncommon in Thais. There is an
      association between BPA exposure and IGT, but not type 2 diabetes.

PMID- 28516807
TI  - Neurofeedback-Based Enhancement of Single Trial Auditory Evoked Potentials:
      Feasibility in Healthy Subjects.
AB  - Previous studies showed a global reduction of the event-related potential
      component N100 in patients with schizophrenia, a phenomenon that is even more
      pronounced during auditory verbal hallucinations. This reduction assumingly
      results from dysfunctional activation of the primary auditory cortex by inner
      speech, which reduces its responsiveness to external stimuli. With this study, we
      tested the feasibility of enhancing the responsiveness of the primary auditory
      cortex to external stimuli with an upregulation of the event-related potential
      component N100 in healthy control subjects. A total of 15 healthy subjects
      performed 8 double-sessions of EEG-neurofeedback training over 2 weeks. The
      results of the used linear mixed effect model showed a significant active
      learning effect within sessions ( t = 5.99, P < .001) against an unspecific
      habituation effect that lowered the N100 amplitude over time. Across sessions, a
      significant increase in the passive condition ( t = 2.42, P = .03), named as
      carry-over effect, was observed. Given that the carry-over effect is one of the
      ultimate aims of neurofeedback, it seems reasonable to apply this neurofeedback
      training protocol to influence the N100 amplitude in patients with schizophrenia.
      This intervention could provide an alternative treatment option for auditory
      verbal hallucinations in these patients.

PMID- 28516808
TI  - Implication of foam sclerosant inactivation by human whole blood in a laboratory
      setting.
AB  - Background During sclerotherapy, it has been recommended to confirm intravenous
      placement of the needle by aspirating blood into the sclerosant syringe. This may
      inactivate some, or all of the sclerosant. Aims To quantify the volume of human
      blood needed to completely inactivate 1 ml of sodium tetradecyl sulphate, and
      comparing fresh blood and blood that has been stored in an
      ethylenediaminetetraacetic acid tube. Methods A series of manual titrations were
      carried out following a procedure developed at STD Pharmaceutical Products Ltd
      (Hereford, UK) and listed in the British Pharmacopeia. Three percent of sodium
      tetradecyl sulphate stock solutions were made with increasing volumes of blood
      and titrated against benzethonium chloride to determine the active concentration
      (% w/v) of sodium tetradecyl sulphate remaining in the solution. Results A
      calculated approximation showed 0.3 ml of blood is required to fully inactivate 1
      ml of 3% sodium tetradecyl sulphate when made into a foam. A comparison was made
      between the use of fresh blood and blood stored in ethylenediaminetetraacetic
      acid tubes. Blood stored in ethylenediaminetetraacetic acid tubes showed more
      inactivation of sodium tetradecyl sulphate, but this was not significant at the P
      <= 0.05 level. Conclusion The data from our study have shown that a minimum of
      0.3 ml of fresh blood is required to inactivate 1 ml of 3% sodium tetradecyl
      sulphate as a foam and it is not significantly affected by storing blood in an
      ethylenediaminetetraacetic acid tube. Our methodology suggests that during foam
      sclerotherapy treatment, blood should not be aspirated into the syringe to
      confirm position, and that ultrasound guidance is more appropriate for needle
      placement.

PMID- 28516809
TI  - Real-time MRI-guided percutaneous sclerotherapy treatment of venous low-flow
      malformations in the head and neck.
AB  - Purpose This manuscript describes the technique of real-time MRI-guided
      sclerotherapy for low-flow venous malformations in the head and neck based on our
      institutional experience. Materials and methods Ethanolamine oleate is used as
      the sclerosant and is mixed with gadolinium for visualization during the
      procedure. The five procedural steps include: (I) an initial tri-plane T2
      weighted sequence to visualize the lesion; (II) a T1 FSE or trueFISP sequence to
      assess needle placement and advancement within the lesion; (III) a tri-plane T1
      FLASH sequence to monitor sclerosant injection; (IV) a T1 FSE or VIBE sequence to
      assess sclerosant coverage of the malformation before needle removal; (V) a post
      procedural tri-plane T1 fat-saturated sequence to confirm sclerosant coverage of
      the lesion. Periprocedural medications typically include steroids, antibiotic
      prophylaxis, and non-steroidal anti-inflammatory medication. Patients are
      typically admitted for overnight observation. Conclusion Real-time MRI-guided
      sclerotherapy for low-flow venous malformations in the head and neck is effective
      and safe.

PMID- 28516811
TI  - European Board of Hand Surgery Diploma Examination 2016 (20-21 June, 2016,
      Santander, Spain).

PMID- 28516810
TI  - The role of meaning in life: mediating the effects of perceived knowledge of
      stroke on depression and life satisfaction among stroke survivors.
AB  - OBJECTIVE: Meaning-making is a way of coping when facing adverse events. A
      paucity of literature suggests other possible factors (e.g. delivery of
      knowledge) can influence how chronic illness survivors (i.e. stroke survivors in
      rehabilitation) cope with illness. This article explores the importance and
      significance of meaning in life as a mediator between perceived stroke knowledge
      and psychological wellbeing among stroke survivors and how such processes can be
      applied in practice to promote their psychological wellbeing. METHODS: A sample
      of N = 192 elderly aged 60 or above who experienced a recent stroke completed a
      survey to assess their levels of cognitive ability, physical function, perceived
      knowledge of stroke, meaning in life, life satisfaction, and depression.
      Correlation and mediation analyses using the Sobel test were conducted to clarify
      the role of meaning in life among stroke survivors. RESULTS: Both perceived
      knowledge of stroke ( r = 0.35, P < 0.001) and meaning in life had positive
      correlations with life satisfaction ( r = 0.37, P < 0.001) and a negative
      correlation with depression. Analyses revealed that meaning in life is a
      significant mediator between perceived knowledge of stroke and depression ( z = 
      3.71, P < 0.001) and between perceived knowledge of stroke and life satisfaction
      ( z = 3.97, P < 0.001) in two separate models. CONCLUSION: The role of meaning in
      life is clear and can affect the dynamics between knowledge of stroke and one's
      psychological wellbeing.

PMID- 28516813
TI  - Evidence based? Eminence based? We need both.

PMID- 28516812
TI  - Hand surgery in Sweden.

PMID- 28516814
TI  - British Society for Surgery of the Hand.

PMID- 28516817
TI  - Decreased, but still sufficient, iodine intake of children and adults in the
      Netherlands.
AB  - Sufficient I intake is important for the synthesis of thyroid hormones, which
      play an important role in normal growth and development. Our aim was to estimate
      habitual I intake for the Dutch population and the risk of inadequate or
      excessive intakes. Further, we aimed to provide an insight into the dietary
      sources of I and the association with socio-demographic factors. Data from the
      Dutch National Food Consumption Survey 2007-2010 (n 3819; 7-69 years), and from
      the Dutch food and supplement composition tables were used to estimate habitual I
      intake with a calculation model. Contribution of food groups to I intake were
      computed and multiple linear regression was used to examine associations of
      intakes with socio-demographic factors. A total of <=2 % of the population had an
      intake below the estimated average requirement or above the upper level. The main
      sources of I were bread containing iodised salt (39 %), dairy products (14 %) and
      non-alcoholic drinks (6 %). I intake (natural sources only, excluding iodised
      salt and supplements) was positively associated with (parental) education, which
      could at least partly be attributed to a higher consumption of dairy products.
      Among children, the consumption of bread, often containing iodised bakery salt,
      was positively associated with parental education. The I intake of the Dutch
      population (7-69 years) seems adequate, although it has decreased since the
      period before 2008. With the current effort to reduce salt intake and changing
      dietary patterns (i.e. less bread, more organic foods) it is important to keep a
      close track on the I status, important sources and potential risk groups.

PMID- 28516819
TI  - Temporal features of word-initial /s/+stop clusters in bilingual Mandarin-English
      children and monolingual English children and adults.
AB  - This study investigated the durational features of English word-initial /s/+stop
      clusters produced by bilingual Mandarin (L1)-English (L2) children and
      monolingual English children and adults. The participants included two groups of
      five- to six-year-old bilingual children: low proficiency in the L2 (Bi-low) and
      high proficiency in the L2 (Bi-high), one group of age-matched English children,
      and one group of English adults. Each participant produced a list of English
      words containing /sp, st, sk/ at the word-initial position followed by /a, i, u/,
      respectively. The absolute durations of the clusters and cluster elements and the
      durational proportions of elements to the overall cluster were measured. The
      results revealed that Bi-high children behaved similarly to the English
      monolinguals whereas Bi-low children used a different strategy of temporal
      organization to coordinate the cluster components in comparison to the English
      monolinguals and Bi-high children. The influence of language experience and
      continuing development of temporal features in children were discussed.

PMID- 28516818
TI  - The changing epidemiology of spinal tuberculosis: the influence of international
      immigration in Catalonia, 1993-2014.
AB  - The overall incidence of spinal tuberculosis (TB) appears to be stable or
      declining in most European countries, but with an increasing proportion of cases
      in the foreign-born populations. We performed a retrospective observational study
      (1993-2014), including all cases of spinal TB diagnosed at a Barcelona hospital
      to assess the epidemiological changes. Fifty-four episodes (48.1% males, median
      age 52 years) of spinal TB were diagnosed. The percentage of foreign-born
      residents with spinal TB increased from 14% to 45.2% in the last 10 years (P =
      0.017). Positive Mycobacterium tuberculosis testing in vertebral specimens was
      88.2% (15/17) for GeneXpert MTB/RIF. Compared with natives, foreign-born patients
      were younger (P < 0.01) and required surgery more often (P = 0.003) because of
      higher percentages of paravertebral abscess (P = 0.038), cord compression (P =
      0.05), and persistent neurological sequelae (P = 0.05). In our setting, one-third
      of spinal TB cases occurred in non-native residents. Compared with natives,
      foreign-born patients were younger and had greater severity of the disease. The
      GeneXpert MTB/RIF test may be of value for diagnosing spinal TB.

PMID- 28516820
TI  - Blogging in Infectious Diseases and Clinical Microbiology: Assessment of
      'Blogosphere' Content.
AB  - OBJECTIVE To analyze influential infectious diseases, antimicrobial stewardship,
      infection control, or medical microbiology blogs and bloggers SETTING World wide
      web DESIGN We conducted a systematic search for blogs in accordance with the
      PRISMA guidelines in September 2015. METHODS A snowball sampling approach was
      applied to identify blogs using various search engines. Blogs were eligible if
      they (1) focused on infectious diseases, antimicrobial stewardship, infection
      control, or medical microbiology; (2) were intended for health professionals; and
      (3) were written in English and (4) were updated regularly. We mapped blog and
      blogger characteristics and used an innovative tool to assess the architecture
      and content of the included blogs. The motivations and perceptions of bloggers
      and readers were also assessed. RESULTS A total of 88 blogs were identified.
      Moreover, 28 blogs (32%) focused on infectious diseases, 46 (52%) focused on
      medical microbiology, and 14 (16%) focused on infection control or antimicrobial
      stewardship. Bloggers were mainly male with medical doctorates and/or PhDs; 32
      bloggers (36%) posted at least weekly; and 51 (58%) had a research purpose. The
      aims were considered clear for 23 blogs (26%), and the field covered was
      considered broad for 25 blogs (28%). Presentation was considered good for 22
      blogs (25%), 51 blogs (58%) were easy to read, and 46 blogs (52%) included expert
      interpretation. Among the top 10 blogs, 3 focused on infectious diseases, 6
      focused on medical microbiology, and 2 focused on infection control (2 were
      equally ranked). The bloggers we questioned were motivated to share their
      independent expertise and opinions. Readers appreciated the concise messages on
      scientific topics and practical updates. CONCLUSIONS This study describes high
      level blogs in the fields of infectious diseases, infection control, and medical
      microbiology. Our findings suggest ways in which bloggers should build/orientate
      blogs for readers, and we have highlighted current gaps in blog topics such as
      antimicrobial stewardship. Infect. Control Hosp. Epidemiol 2017;38:832-839.

PMID- 28516821
TI  - Pseudomonas aeruginosa Outbreak in a Neonatal Intensive Care Unit Attributed to
      Hospital Tap Water.
AB  - OBJECTIVE To investigate an outbreak of Pseudomonas aeruginosa infections and
      colonization in a neonatal intensive care unit. DESIGN Infection control
      assessment, environmental evaluation, and case-control study. SETTING Newly built
      community-based hospital, 28-bed neonatal intensive care unit. PATIENTS Neonatal
      intensive care unit patients receiving care between June 1, 2013, and September
      30, 2014. METHODS Case finding was performed through microbiology record review.
      Infection control observations, interviews, and environmental assessment were
      performed. A matched case-control study was conducted to identify risk factors
      for P. aeruginosa infection. Patient and environmental isolates were collected
      for pulsed-field gel electrophoresis to determine strain relatedness. RESULTS In
      total, 31 cases were identified. Case clusters were temporally associated with
      absence of point-of-use filters on faucets in patient rooms. After adjusting for
      gestational age, case patients were more likely to have been in a room without a
      point-of-use filter (odds ratio [OR], 37.55; 95% confidence interval [CI], 7.16
      infinity). Case patients had higher odds of exposure to peripherally inserted
      central catheters (OR, 7.20; 95% CI, 1.75-37.30) and invasive ventilation (OR,
      5.79; 95% CI, 1.39-30.62). Of 42 environmental samples, 28 (67%) grew P.
      aeruginosa. Isolates from the 2 most recent case patients were indistinguishable
      by pulsed-field gel electrophoresis from water-related samples obtained from
      these case-patient rooms. CONCLUSIONS This outbreak was attributed to
      contaminated water. Interruption of the outbreak with point-of-use filters
      provided a short-term solution; however, eradication of P. aeruginosa in water
      and fixtures was necessary to protect patients. This outbreak highlights the
      importance of understanding the risks of stagnant water in healthcare facilities.
      Infect Control Hosp Epidemiol 2017;38:801-808.

PMID- 28516822
TI  - Key drivers of patient experience in ambulatory paediatric cardiology.
AB  - Patient experience is becoming a central focus of healthcare. A broad range of
      studies on how to increase patient satisfaction ratings exists; however, they
      lack the specificity to adequately guide physicians and hospitals on how to
      improve patient experience. The objective of this study was to define the aspects
      of patient experience within paediatric cardiologist practices that can serve as
      predictors of excellent patient satisfaction. From 1 January, 2013 to 28
      February, 2015 (26 months), outpatients who visited paediatric cardiologists were
      asked to complete a 39-question patient satisfaction survey regarding their
      experience. Surveys were collected over a 26-month period by Press Ganey, an
      independent provider of patient satisfaction surveys. Participants were asked to
      rate their experience on a 1-5 Likert-scale: a score of 1 demonstrated a "poor"
      experience, whereas a score of 5 demonstrated a "very good" experience. This
      retrospective study of 2468 responses determined that cheerfulness of the
      practice (r=0.85, p<0.001), a cohesive staff (r=0.83, p<0.001), and a care
      provider explaining problems and conditions (r=0.81, p<0.001) were key aspects of
      a paediatric cardiologist's practice that can be used as predictors of overall
      patient satisfaction. Awareness of how doctors can personalise a patient's
      experience is vital to achieve greater patient satisfaction and, ultimately,
      better patient outcomes.

PMID- 28516824
TI  - Opinion paper: Smell: an affordable way to improve livestock welfare.

PMID- 28516823
TI  - Predictors of health-related quality of life in children with chronic heart
      disease.
AB  - OBJECTIVE: Chronic paediatric heart disease is often associated with residual
      symptoms, persisting functional restrictions, and late sequelae for psychosocial
      development. It is, therefore, increasingly important to evaluate the health
      related quality of life of children and adolescents with chronic heart disease.
      The aim of this study was to determine medical and socio-demographic variables
      affecting health-related quality of life in school-aged children and adolescents
      with chronic heart disease. Patients and methods The Pediatric Cardiac Quality of
      Life Inventory was administered to 375 children and adolescents and 386 parental
      caregivers. Medical information was obtained from the charts. The socio
      demographic information was provided by the patients and caregivers. RESULTS:
      Greater disease severity, low school attendance, current cardiac medication,
      current parental employment, uncertain or limited prognosis, history of
      connection to a heart-lung machine, number of nights spent in a hospital, and
      need for treatment in a paediatric aftercare clinic independently contributed to
      lower health-related quality of life (self-report: R2=0.41; proxy-report:
      R2=0.46). High correlations between self-reports and parent-proxy reports
      indicated concordance regarding the evaluation of a child's health-related
      quality of life. CONCLUSIONS: Beyond medical treatment, integration into school
      is important to increase health-related quality of life in children and
      adolescents surviving with chronic heart disease. Regular screening of health
      related quality of life is recommended to identify patients with special needs.

PMID- 28516825
TI  - Girls' and boys' trajectories of appearance anxiety from age 10 to 15 years are
      associated with earlier maturation and appearance-related teasing.
AB  - Adolescents' appearance-related concerns can provoke increasing emotional,
      social, and eating-related problems. The aims of this five-wave (2.5-year),
      multiple-informant longitudinal study were to (a) examine growth trajectories of
      appearance anxiety symptoms and appearance esteem, (b) identify whether
      trajectories differed by gender, and (c) examine several launching factors
      including parent-reported physical maturation, peer-rated physical appearance,
      body mass index, and appearance teasing by parents and peers. Participants were
      387 adolescents (44% boys) aged 10 to 13 years at the first assessment. Steep
      growth in appearance anxiety symptoms was found for both girls and boys, but
      there was no average change in appearance esteem. Girls had more elevated
      appearance anxiety symptoms and lower appearance esteem than boys, girls' body
      mass index was associated with symptoms, and earlier physical maturation and
      teasing about appearance, alone and in combination, were associated with growth
      in appearance anxiety symptoms for girls and boys. Earlier maturing boys who were
      highly teased by parents, but even more so when teased by peers, were at utmost
      risk for elevated appearance anxiety symptoms and increasing symptoms over time.
      In contrast, all girls exhibited elevated or increasing appearance anxiety
      symptoms across time, with the exception of girls with the latest maturation who
      also reported little teasing about their appearance.

PMID- 28516827
TI  - BOLD activation of the ventromedial prefrontal cortex in patients with late life
      depression and comparison participants.
AB  - ABSTRACTThe ventromedial prefrontal cortex's (vMPFC) role in regulating emotions
      in late life depression (LLD) remains unclarified. We assessed vMPFC activation
      in an emotional valence blood oxygenation level-dependent (BOLD) functional
      magnetic neuroimaging (fMRI) task and related the findings to extent of white
      matter hyperintensities (WMH). Sixteen participants with mild to moderate LLD
      were compared to 14 similar aged comparison participants. Participants in the
      scanner viewed words matched for length and arousal, indicated the perceived
      valence by pressing one of the three buttons i.e. "positive, negative, or
      neutral." WMH volume was greater in LLD participants than comparison
      participants. There were no differences in activations between groups to any
      valence contrast. Female LLD participants showed greater activation for negative
      versus positive and negative versus neutral words as compared to female
      comparison participants. Female LLD participants respond differently to
      emotionally laden words compared to comparison participants. WMH could play a
      role in etiopathology of emotional perception in female LLD participants.

PMID- 28516826
TI  - Fatalities from Firearm-Related Injuries in Selected Governorates of Iraq, 2010
      2013.
AB  - BACKGROUND: In Iraq, where Islamic State of Iraq and Syria (ISIS) and other
      groups have contributed to escalating violence in recent years, understanding the
      epidemiology of intentional firearm-related fatalities is essential for public
      health action. METHODS: The Iraqi Ministry of Health (MoH; Baghdad, Iraq)
      compiles surveillance of fatal injuries in eight of Iraq's 18 governorates
      (Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya).
      Information is collected from coroner's reports and interviews with family
      members. Analysis was performed on intentional firearm-related injuries,
      excluding injuries from intentional self-harm or negligent discharges, that
      occurred during 2010-2013, a subset of all fatal injuries, and compared to
      previously published explosive-related fatalities. RESULTS: Overall, the dataset
      included 7,985 firearm-related fatalities. Yearly fatalities were: 2010=1,706;
      2011=1,642; 2012=1,662; and 2013=2,975. Among fatalities, 86.0% were men and
      13.7% women; 83.4% were adults and 6.2% children <18 years of age. Where age and
      sex were both known, men aged 20-39 years accounted for 56.3% of fatalities.
      Three "high-burden" governorates had the highest fatality rate per 100,000
      population-Baghdad (12.9), Ninevah (17.0), and Al-Anbar (14.6)-accounting for
      85.9% of fatalities recorded in the eight governorates. Most fatalities occurred
      in the street (56.3%), followed by workplace (12.2%), home (11.3%), and
      farm/countryside (8.4%). Comparing the ratio of firearm-related fatalities to
      explosives-related fatalities revealed an overall ratio of 2.8:1. The ratio in
      Baghdad more than doubled from 2.9 in 2010 to 6.1 in 2013; the highest ratios
      were seen outside the high-burden governorates. CONCLUSIONS: Firearm-related
      fatalities remained relatively stable throughout 2010-2012, and almost doubled in
      2013, correlating with increased ISIS activity. Three governorates contributed
      the majority of fatalities and experienced the highest fatality rates; these saw
      high levels of conflict. Firearm-related fatalities disproportionately affected
      younger men, who historically are over-represented as victims and perpetrators of
      violence. More than one-half of fatalities occurred in the street, indicating
      this as a common environment for conflict involving firearms. Firearms appear to
      account for more fatalities in Iraq than explosives and largely accounted for
      escalating violence in Baghdad during the study period. The high ratio observed
      outside the high-burden governorates is reflective of very low numbers of
      explosives-related fatalities; thus, violence in these governorates is likely non
      conflict-related. These observations provide valuable public health information
      for targeted intervention to prevent violence. Nerlander MP , Leidman E , Hassan
      A , Sultan ASS , Hussain SJ , Browne LB , Bilukha OO . Fatalities from firearm
      related injuries in selected governorates of Iraq, 2010-2013. Prehosp Disaster
      Med. 2017;32(5):548-555.

PMID- 28516828
TI  - Impact on the medical decision-making process of multiplex PCR assay for
      respiratory pathogens.
AB  - The objective of this study was to determine how clinicians make use of the
      modern multiplex PCR assays (MPAs) to manage patients hospitalized for community
      acquired pneumonia (CAP). We studied the use of MPAs in 1648 patients
      hospitalized for CAP over a 3-year period at the moment of the setup of the new
      PCR assay. We observed that the use of MPAs for the identification of multiple
      respiratory pathogens marks a radical change in the investigation of CAP
      etiology. Surprisingly, the contribution of MPAs to the medical decision-making
      process varies drastically according to the units of care.

PMID- 28516829
TI  - Factors associated with failure of emergency wait-time targets for high acuity
      discharges and intensive care unit admissions.
AB  - OBJECTIVE: Ontario established emergency department length-of-stay (EDLOS)
      targets but has difficulty achieving them. We sought to determine predictors of
      target time failure for discharged high acuity patients and intensive care unit
      (ICU) admissions. METHODS: This was a retrospective, observational study of 2012
      Sunnybrook Hospital emergency department data. The main outcome measure was
      failing to meet government EDLOS targets for high acuity discharges and ICU
      emergency admissions. The secondary outcome measures examined factors for low
      acuity discharges and all admissions, as well as a run chart for 2015 - 2016 ICU
      admissions. Multiple logistic regression models were created for admissions, ICU
      admissions, and low and high acuity discharges. Predictor variables were at the
      patient level from emergency department registries. RESULTS: For discharged high
      acuity patients, factors predicting EDLOS target failure were having physician
      initial assessment duration (PIAD)>2 hours (OR 5.63 [5.22-6.06]), consultation
      request (OR 10.23 [9.38-11.14]), magnetic resonance imaging (MRI) (OR 19.33
      [12.94-28.87]), computed tomography (CT) (OR 4.24 [3.92-4.59]), and ultrasound
      (US) (OR 3.47 [3.13-3.83]). For ICU admissions, factors predicting EDLOS target
      failure were bed request duration (BRD)>6 hours (OR 364.27 [43.20-3071.30]) and
      access block (AB)>1 hour (OR 217.27 [30.62-1541.63]). For discharged low acuity
      patients, factors predicting failure for the 4-hour target were PIAD>2 hours (OR
      15.80 [13.35-18.71]), consultation (OR 20.98 [14.10-31.22]), MRI (OR 31.68 [6.03
      166.54]), CT (OR 16.48 [10.07-26.98]), and troponin I (OR 13.37 [6.30-28.37]).
      CONCLUSION: Sunnybrook factors predicting failure of targets for high acuity
      discharges and ICU admissions were hospital-controlled. Hospitals should
      individualize their approach to shortening EDLOS by analysing its patient
      population and resource demands.

PMID- 28516830
TI  - Childhood Victimization, Attachment, Coping, and Substance Use Among Victimized
      Women on Probation and Parole.
AB  - Justice-involved women report high rates of victimization across their life span,
      and these experiences contribute to their involvement in the criminal justice
      (CJ) system. Within this population, research has identified an overlap among
      victimization and substance use, a high-risk coping mechanism. Furthermore,
      research indicates attachment style is related to coping and high-risk behaviors.
      Research is needed to understand the relationship among these mechanisms as they
      relate to intimate partner violence (IPV). To address this gap, this study
      investigated the relationship between attachment, coping, childhood
      victimization, substance use, and IPV among 406 victimized women on
      probation/parole. Results of 6 multivariate regression analyses were
      statistically significant, accounting for 8%-13% of the variance in IPV.
      Particularly, childhood sexual victimization and negative coping were significant
      in all analyses. Findings provide practitioners, administrators, and policymakers
      information about the specific needs of justice-involved women.

PMID- 28516831
TI  - An Exploration of the Mediators Between Childhood Maltreatment and Intimate
      Partner Violence.
AB  - Intimate partner violence (IPV) is associated with numerous long-term
      consequences and warrants significant clinical attention. Recent theoretical
      models and empirical research have suggested that several factors play a role in
      the development of IPV perpetration, including childhood maltreatment, early
      maladaptive schemas, anger, and difficulties in emotion regulation. This study
      investigated the relationship between childhood maltreatment and IPV,
      specifically examining the mediation of this relationship by several variables
      thought to be related to this pernicious problem, including early maladaptive
      schemas, the experience of anger, and emotion regulation difficulties. In a young
      adult collegiate sample of 110 women in relationships, results of a bootstrapped
      multiple mediation analysis supported the hypothesis that childhood maltreatment
      predicted physical aggression within intimate partner relationships and found
      that the total indirect effect of childhood maltreatment on physical aggression
      through the 3 proposed mediators was significant. However, consistent with recent
      empirical findings, only difficulties in emotion regulation significantly
      mediated the relationship between childhood maltreatment and physical aggression
      within the sample.

PMID- 28516832
TI  - The Neighborhood Context of Hate Crime: A Comparison of Violent and Property
      Offenses Using Rare Events Modeling.
AB  - Many studies into the antecedents of hate crime in the neighborhood combine
      offense categories, meaning that it is unclear whether or not there are distinct
      contextual factors associated with violent and property hate offenses. This study
      uses rare events modeling to examine the household and neighborhood factors
      associated with violent and property offenses. Using the Australian Community
      Capacity Study, the study focuses on the neighborhood characteristics influencing
      self-reported violent and property hate crime for 4,396 residents in Brisbane.
      Findings demonstrate important differences between the offense types. Violence is
      predicted by household renting and non-English language, whereas property
      offenses are predicted by household non-English language, neighborhood median
      income, and change in non-English-speaking residents. In both offense types,
      neighborhood place attachment acts as a protective factor. These findings
      highlight the theoretical implications of combining distinct hate crime types for
      methodological reasons.

PMID- 28516835
TI  - Modifying Self-Blame, Self-Esteem, and Disclosure Through a Cooperative Cross-Age
      Teaching Intervention for Bullying Among Adolescents.
AB  - Bullying is common among school students, and some victims hold self-blaming
      attributions, exhibit low self-esteem, and do not seek social support. A wait
      list control pre-/post-test experimental design, with random allocation, was used
      to assess the effects of a novel cross-age teaching of social issues (CATS)
      intervention on the latter 3 variables among peer-identified victims of bullying
      (N = 41, mean age = 14.5 years). In small cooperative groups of classmates,
      participants designed and delivered a lesson to younger students that informed
      them that bullies not victims are in the wrong, victims have no reason to feel
      bad about themselves, and that seeking help can be beneficial. CATS led to a
      significant improvement on all 3 dependent variables with mostly large effect
      sizes; these positive effects were even stronger with a bigger dose of
      intervention (6 hr vs. 4 hr), and changes in self-blame, and separately changes
      in self-esteem, mediated the positive effect of the intervention on help-seeking.
      The theoretical and practical implications of these results were discussed,
      especially in terms of supporting a highly vulnerable subgroup of adolescents.

PMID- 28516836
TI  - A Review and Assessment of Intimate Partner Violence Interventions and Trainings
      for Service Providers and Frontline Staff.
AB  - Despite a long history of various service providers' interactions with the
      survivors of intimate partner violence (IPV), previous reviews of interventions
      for service providers addressing IPV have only focused on those employed in
      medical settings. This review closely examines evidence related to interventions
      for service providers and frontline staff in nonmedical settings to identify
      effective interventions to address IPV and assist IPV survivors. Using explicit
      criteria, 16 studies were included in this review. This review offers a synthesis
      of the 16 studies by illuminating types of the interventions, outcomes and their
      effectiveness, settings of the interventions, and their quality of design.
      Specific implications are discussed to guide future practice, research, and
      policy.

PMID- 28516837
TI  - Help-Seeking Behavior Among Moroccan, Romanian, and Ecuadorian Women Experiencing
      Intimate Partner Violence in Spain.
AB  - This study aims to identify different types of response to intimate partner
      violence (IPV) and help-related seeking behavior among Spain's most numerous
      immigrant groups-Moroccans, Romanians, and Ecuadorians. Women reporting physical,
      sexual and/or psychological violence by a current or former intimate partner (n =
      194) were selected from a cross-sectional study based on 1,607 surveys (2011).
      There are 84% of surveyed battered women who reported seeking help through
      informal and/or formal channels. The most frequently reported informal help
      seeking behavior was talking with the abusive partner (from 63% to 83%).
      Moroccans identified social services (29.6%) and health care (25.9%)
      professionals as their most frequently used formal resources when seeking help.
      Approximately 32% of Ecuadorians and Romanians declared having reported their
      partners to the police. Among all of the women, seeking help through formal
      channels was more probable in cases where the severity of IPV was high (adjusted
      odds ratio = 5.69, 95% confidence interval [2.29, 14.12]). It is needed to
      increase professionals' opportunities to intervene in cases of IPV before they
      become severe.

PMID- 28516838
TI  - Acute Alcohol Use, History of Homelessness, and Intent of Injury Among a Sample
      of Adult Emergency Department Patients.
AB  - BACKGROUND: The literature is clear that adults who are currently homeless also
      have higher rates of intentional injuries, such as assault and suicide attempts.
      No study has assessed whether intentional injuries are exacerbated because of
      substance use among adults with a history of homelessness. METHODS: Data were
      obtained from a cohort of adults admitted to 3 urban emergency departments (EDs)
      in Texas from 2007 to 2010 (N = 596). Logistic regression analyses were used to
      determine whether a history of homelessness was associated with alcohol use at
      time of injury in intentional violent injuries (gunshot, stabbing, or injury
      consistent with assault). RESULTS: 39% adults with a history of homelessness who
      were treated at trauma centers for a violent injury. Bivariate analyses indicated
      that adults who had ever experienced homelessness have 1.67 increased odds, 95%
      confidence interval (CI) [1.11, 2.50], of any intentional violent injury and 1.95
      increased odds (95% CI [1.12, 3.40]) of a stabbing injury than adults with no
      history of homelessness. CONCLUSIONS: Adults who experienced homelessness in
      their lifetime were more likely to visit EDs for violencerelated injuries. Given
      our limited knowledge of the injuries that prompt ED use by currently homeless
      populations, future studies are needed to understand the etiology of injuries,
      and substance-related injuries specifically, among adults with a history of
      homelessness.

PMID- 28516839
TI  - Ethno-Racial Differences in Children's Attitudes and Beliefs About Violence.
AB  - One in 15 children in the United States are exposed to intimate partner violence
      (IPV) each year. Although much is known about the adverse effects of witnessing
      IPV on children, little attention has been given to the impact of IPV on children
      of diverse ethno-racial backgrounds. In particular, the association between IPV
      and children's attitudes and beliefs about violence across different ethno-racial
      populations remains to be explored. One hundred ninety children between the ages
      of 4 and 12 years of varying ethno-racial backgrounds who had witnessed recent
      IPV were interviewed regarding their attitudes and beliefs about IPV. Results
      show that younger children and White, Black, and Biracial children exhibited more
      deleterious attitudes and beliefs about violence after exposure to IPV than did
      older and Latina or Latino children. These findings may indicate the need for
      more tailored intervention programs that target the specific maladaptive beliefs
      expressed by children of various demographic groups.

PMID- 28516841
TI  - Us3 and Us9 proteins contribute to the stromal invasion of bovine herpesvirus 1
      in the respiratory mucosa.
AB  - Bovine herpesvirus 1 (BHV-1) infection may lead to conjunctivitis, upper
      respiratory tract problems, pneumonia, genital disorders and abortion. BHV-1 is
      able to spread quickly in a plaque-wise manner and invade by breaching the
      basement membrane (BM) barrier in the respiratory mucosa. BHV-1 Us3, a
      serine/threonine kinase, induces a dramatic cytoskeletal reorganization and BHV-1
      Us9, a tail-anchored membrane protein, is required for axonal transport of
      viruses in neurons. In this study, we investigated the role of Us3 and Us9 during
      BHV-1 infection in the respiratory mucosa. First, we constructed and
      characterized BHV-1 Us3 null, Us9 null and revertant viruses. Then, we analysed
      the viral replication and plaque size (latitude) in Madin-Darby bovine kidney
      (MDBK) cells and the respiratory mucosa as well as viral penetration depth
      underneath the BM of the respiratory mucosa when inoculated with these
      recombinant viruses. Knockout of Us3 resulted in a 1 log10 reduction in viral
      titre and plaque size (latitude) in MDBK cells and the trachea mucosa. There were
      no defects in the cell-to-cell spread observed for BHV-1 Us9 null virus. Both BHV
      1 Us3 null and Us9 null viruses showed a significant reduction of plaque
      penetration underneath the BM; however, penetration was not completely inhibited.
      In conclusion, the current findings demonstrated that Us3 and Us9 play an
      important role in the invasion of BHV-1 through the BM of the respiratory mucosa,
      which shows the way forward for research-based attenuation of viruses in order to
      make safer and better-performing vaccines.

PMID- 28516840
TI  - Victim Alcohol Intoxication During a Sexual Assault: Relations With Subsequent
      PTSD Symptoms.
AB  - This study examines associations between women's alcohol intoxication at the time
      of sexual assault and posttraumatic stress disorder (PTSD) symptoms. Drawing on
      the dual representation theory (Brewin, Gregory, Lipton, & Burgess, 2010), we
      hypothesized that intoxication at the time of assault would be positively
      associated with both overall symptoms of PTSD and PTSD reexperiencing symptoms in
      particular. A total of 143 community women (ages 18-26 years; 71.3% European
      American) reporting sexual victimization completed questionnaires assessing
      severity of coercion involved in the assault, perceived level of intoxication at
      the time of assault, and current PTSD symptoms. Overall, results suggested that
      greater alcohol intoxication (but not alcohol use alone) was associated with more
      severe PTSD symptoms when controlling for severity of coercion. Furthermore,
      higher levels of victim intoxication at the time of the assault were most
      predictive of reexperiencing symptoms relative to the other symptom clusters.

PMID- 28516842
TI  - Serotype distribution, antimicrobial resistance and prevalence of pilus islets in
      pneumococci following the use of conjugate vaccines.
AB  - PURPOSE: In Japan, the 7-valent pneumococcal vaccine (PCV7) was introduced in
      2010 and, in 2013, the PCV7 was replaced with the 13-valent pneumococcal vaccine
      (PCV13). This study was conducted to investigate serotypes, antimicrobial
      resistance and prevalence of pilus islets in pneumococcal isolates from
      inpatients in a Japanese tertiary hospital. METHODOLOGY: From April 2011 to
      February 2016, 151 isolates [95 (18 children, 77 adults) and 56 (19 children, 37
      adults) in the PCV7 and PCV13 periods, respectively] were collected. All isolates
      were serotyped using genetic methods and were tested for susceptibility to 18
      antimicrobials. Unaltered penicillin-binding protein (PBP) genes, macrolide
      resistance genes and pilus islets were identified by PCR. RESULTS: Between the
      two periods, the prevalence of non-PCV13 serotypes was shown to increase from
      50.0 to 78.9 % in children, and serotype 3 increased from 14.3 to 24.3 % in
      adults. Six of seven isolates from invasive diseases were assigned to non-PCV13
      serotypes. Overall, multidrug resistance (MDR) was detected in 46.4 % of
      isolates, which included the dominant non-PCV13 serotypes 6E, 15A and 23A
      (prevalence>=75.0 %). gPRSP (three altered genes pbp1a, pbp2b and pbp2x) and
      macrolide resistance genes [erm(B) and/or mef(A/E)] were detected in 35.8 and
      93.4 % of all isolates, respectively. Pilus islets [PI-1 (clade I, II and III)
      and/or PI-2] were found in 22.5 % (34/151) of isolates belonging to six different
      serotypes (19F, 23F, 19A, 6E, 15B and 35B) and 88.2 % (30/34) of these exhibited
      MDR. CONCLUSION: This study revealed the spread of MDR in several non-PCV13
      serotypes and in isolates with pilus islets.

PMID- 28516843
TI  - Potentially hazardous Streptococcus suis strains latent in asymptomatic pigs in a
      major swine production area of Thailand.
AB  - PURPOSE: Carrier pigs have been considered as the major reservoir of
      Streptococcus suis and couldbe a significant source of human infection.
      Therefore, we investigated the prevalence and characteristics of latent S. suis
      in asymptomatic pigs in the pig-farming area of central Thailand, and compared
      the data to those previously reported in other regions. METHODOLOGY: We collected
      samples from 340 asymptomatic pigs. S. suis isolates from the samples were
      confirmed by species-specific PCR (recN PCR). The capsular polysaccharide
      synthesis gene (cps) types, virulence-associated gene profiles and sequence types
      (STs) of the isolates were investigated.Results/Key findings. The prevalence of
      S. suis found in this study was 37 % (125/340 pigs). The most prevalent genotype
      was mrp-/epf-/sly-. Among the 16 cps-types identified in 135 isolates, cps-type
      16 was the most frequent (11 %), whereas 44 % of the isolates were non-typable.
      In common with the strains causing human sepsis in Thailand, two cps-type 9
      isolates and a cps-type 24 isolate from slaughtered pigs belonged to ST16 and
      ST221, respectively. All the isolated cps-type 2 strains were confirmed as
      serotype 2 by co-agglutination tests, and these belonged to ST104, the unique ST
      commonly found in Thai patients; however, in contrast to the endemic areas, the
      prevalence of serotype 2 strains was relatively low (2 %) and no ST1 isolate was
      found. CONCLUSION: Our results showed the population structure differences
      between S. suis in central Thailand and other regions; however, zoonotic S. suis
      is certainly latent in asymptomatic pigs in this intensive swine production area.

PMID- 28516845
TI  - Activity and functional properties of the isocitrate lyase in the cyanobacterium
      Cyanothece sp. PCC 7424.
AB  - Cyanobacteria are ubiquitous photoautotrophs that assimilate atmospheric CO2 as
      their main source of carbon. Several cyanobacteria are known to be facultative
      heterotrophs that are able to grow on diverse carbon sources. For selected
      strains, assimilation of organic acids and mixotrophic growth on acetate has been
      reported for decades. However, evidence for the existence of a functional
      glyoxylate shunt in cyanobacteria has long been contradictory and unclear. Genes
      coding for isocitrate lyase (ICL) and malate synthase were recently identified in
      two strains of the genus Cyanothece, and the existence of the complete glyoxylate
      shunt was verified in a strain of Chlorogloeopsis fritschii. Here, we report that
      the gene PCC7424_4054 of the strain Cyanothece sp. PCC 7424 encodes an
      enzymatically active protein that catalyses the reaction of ICL, an enzyme that
      is specific for the glyoxylate shunt. We demonstrate that ICL activity is induced
      under alternating day/night cycles and acetate-supplemented cultures exhibit
      enhanced growth. In contrast, growth under constant light did not result in any
      detectable ICL activity or enhanced growth of acetate-supplemented cultures.
      Furthermore, our results indicate that, despite the presence of a glyoxylate
      shunt, acetate does not support continued heterotrophic growth and cell
      proliferation. The functional validation of the ICL is supplemented with a
      bioinformatics analysis of enzymes that co-occur with the glyoxylate shunt. We
      hypothesize that the glyoxylate shunt in Cyanothece sp. PCC 7424, and possibly
      other nitrogen-fixing cyanobacteria, is an adaptation to a specific ecological
      niche and supports assimilation of nitrogen or organic compounds during the night
      phase.

PMID- 28516846
TI  - Revealing Victimization: The Impact of Methodological Features in the National
      Crime Victimization Survey.
AB  - This study examines the impact of methodological features of the National Crime
      Victimization Survey (NCVS) on respondent willingness to report violent, serious
      violent, and property victimizations to the NCVS. Bounded and unbounded data from
      the 1999-2005 NCVS are used to create a longitudinal file of respondents, and
      survey-weighted logistic regression models are used to assess the factors
      associated with the reporting of victimization. Net of sociodemographic control
      variables, unbounded interviews produced higher estimates of serious violence
      (72%), violence (66%), and property victimization (67%). Mobile respondents
      reported higher estimates than nonmobile respondents of serious violence (48%),
      violence (35%), and property victimization (15%). Compared with in-person
      interviews, interviewing by telephone increased reporting for serious violence
      (7%), violence (12%), and property victimization (17%). This study highlights the
      importance of controlling for these factors in both longitudinal and cross
      sectional analyses to estimate victimization risk.

PMID- 28516844
TI  - Clues for two-step virion infectivity factor regulation by core binding factor
      beta.
AB  - Lentiviruses threaten human and animal health. Virion infectivity factor (Vif) is
      essential for the infectivity of most lentiviruses, except for the equine
      infectious anaemia virus (EIAV). Vif promotes viral infectivity by recruiting a
      Cullin-based E3 ligase to induce the degradation of a class of host restriction
      factors, named APOBEC3. Core binding factor beta (CBF-beta) is necessary for
      several primate lentiviral Vif functions, including HIV-1 Vif. Although much
      progress has been made in understanding the contribution of CBF-beta to Vif
      function, the precise mechanism has not yet been fully elucidated. In this study,
      we found that an interaction with CBF-beta altered the oligomerization and
      subcellular distribution pattern and increased the stability of two primate
      lentiviral Vifs, HIV-1 Vif and Macaca simian immunodeficiency virus (SIVmac) Vif.
      Moreover, using a CBF-beta loss-of-function mutant, we demonstrated that the
      interaction between CBF-beta and Vif was not sufficient for Vif assistance; a
      region including F68 in CBF-beta was also required for the stability and function
      of Vif. For the first time, this study separates the binding and regulating
      processes of CBF-beta when it is promoting Vif function, which further extends
      our understanding of the biochemical regulation of Vif by CBF-beta.

PMID- 28516848
TI  - The Role of Psychopathic Traits in Female Sexual Coercion.
AB  - Researchers have consistently found a relationship between psychopathy and the
      use of sexual coercion in samples of males with and without previous sexual
      arrests (Abbey, Jacques-Tiura, & LeBreton, 2011; Hare, 1991; Hersh & Gray-Little,
      1998; Seto & Lalumiere, 2000). Although there is growing recognition that females
      also engage in sexually coercive behavior, current understanding of female
      coercion is limited (Bouffard, Bouffard, & Miller, 2015; Cortoni, Hanson, &
      Coache, 2010; Munoz, Khan, & Cordwell, 2011). This study examined the
      relationship between psychopathic traits and sexual coercion tactics among a
      sample of 558 undergraduate females. Results indicate that the use of any
      previous sexual coercion tactic (coax, lie, get drunk, and assault) and higher
      endorsement of primary psychopathy traits significantly predict whether the
      females state that they will engage in future sexually coercive behaviors.

PMID- 28516847
TI  - Who Is at Risk for Intimate Partner Violence Victimization: Using Latent Class
      Analysis to Explore Interpersonal Polyvictimization and Polyperpetration Among
      Pregnant Young Couples.
AB  - The purpose of our study was (a) to use latent class analyses to identify
      subgroups of interpersonal polyvictimization and polyperpetration among young
      pregnant couples and (b) examine actor-partner effects of latent classes on
      current intimate partner violence (IPV) victimization. Data were collected from
      296 pregnant young couples recruited at obstetrics and gynecology clinics. A 3
      latent class model emerged for women: Polyvictim-Polyperpetrator, Nonvictim
      Nonperpetrator, and Community and Prior IPV Victim. A 4-latent class model
      emerged for men: Community and Prior IPV Victim, Polyvictim-Nonpartner
      Perpetrator, Prior IPV and Peer Victim, and Nonvictim-Nonperpetrator. Using the
      actor-partner independence model, actor effects of the women's Polyvictim
      Polyperpetrator class and men's Polyvictim-Nonpartner Perpetrator class related
      to greater odds of IPV victimization compared to women and men in the Nonvictim
      Nonperpetrator classes.

PMID- 28516849
TI  - Identification of Nonfatal Strangulation by 911 Dispatchers: Suggestions for
      Advances Toward Evidence-Based Prosecution.
AB  - Research highlights the need for systematic law enforcement training on nonfatal
      strangulation in domestic violence situations to improve evidence-based
      prosecution of these violent felonies. However, most of this research focuses on
      the role of police officers in the safety response. Although often overlooked,
      this research examines the role of 911 dispatchers, who are many times the first
      person the victim calls for assistance. This study examines official domestic
      violence records, gathered through a partnership with a County Sheriff's agency,
      to determine whether domestic violence strangulation is being adequately
      identified and documented by first responders. This research highlights the need
      for considering 911 dispatchers as having a potentially critical role in a
      comprehensive response to domestic violence strangulation from initial screening
      to eventual prosecution.

PMID- 28516850
TI  - Are Men With a History of Head Injury Less Responsive to Cognitive Behavioral
      Therapy for Intimate Partner Violence?
AB  - Head injury is highly prevalent among intimate partner violence (IPV) offenders.
      This study investigates responsiveness to cognitive behavioral therapy (CBT) for
      partnerviolent men with and without a history of head injury using archival data
      on 310 males seeking IPV counseling at a community domestic violence agency.
      Participants reported on their history of head injury, age at injury, and length
      of time unconscious in a structured interview at program intake. Criminal justice
      outcomes were assessed for the 2-year period after scheduled completion of
      treatment using a publicly available state database. A significantly greater
      percentage of men with a history of head injury (N = 84) than those without (N =
      226) had criminal involvement for incidents of partner abuse during the follow-up
      period. In addition, men with a history of moderate-to-severe head injury (n =
      25) had more criminal involvement for general violence than those with no history
      of head injury. The findings highlight the need to screen partner-violent men for
      head injury and to develop and investigate intervention enhancements for those
      individuals.

PMID- 28516851
TI  - Intimate Partner Abuse and Attachment: A Comparison Between Abused and Nonabused
      Women.
AB  - The purpose of this study was to examine intimate partner abuse (IPA), parental
      attachment, and romantic attachment among college women. More specifically, IPA
      was examined such that women who had experienced abuse and those who had not were
      compared with respect to parental and romantic attachment using the lens of
      attachment theory. Undergraduate women (N = 502) completed an online survey
      assessing their experiences of IPA as well as their parental and romantic
      attachment styles. Bivariate correlations demonstrated that IPA was significantly
      associated with all study variables (i.e., love withdrawal, care, and
      overprotection from both mother and father; romantic anxiety) in the hypothesized
      directions with the exception of romantic avoidance not being associated with
      abuse. Regarding the comparison of women who had experienced abuse (n = 367) to
      women who had not experienced abuse (n = 135), one-way analyses of variance
      (ANOVAs) revealed significant group mean differences in the hypothesized
      directions between abused and nonabused women with respect to love withdrawal and
      overprotection from both mothers and fathers, and romantic anxiety. In addition,
      psychological IPA and physical IPA were examined separately, yielding additional
      group differences regarding care from father and care from both mother and
      father, respectively. This work begins to examine attachment and IPA in new ways
      because it examines both parental attachment and romantic attachment in relation
      to IPA.

PMID- 28516853
TI  - A Gendered Analysis of the Shadow of Sexual Harm Among a College Sample.
AB  - This study uses survey methodology to examine correlates of fear of crime among
      men and women to discern the unique impact of risk perception, victimization,
      vicarious victimization, and fear of sexual harm on fear of crime. Recently,
      scholars have begun to examine fear separately by gender, which is vital given
      the unique experiences men and women have with fear and victimization. We examine
      two different types of fear of crime to determine whether the effects of these
      correlates differ by crime type across gender. Results suggest that fear of
      sexual harm and risk perception are the most important indicators of fear of
      crime for both genders; sexual harm fear is particularly impactful for female
      fear of violence. Race and ethnicity also have interesting impacts for male fear
      of violent crime because racial and ethnic minorities indicate more fear of
      violent crime than White males. The findings illustrate how imperative it is to
      continue to examine fear of specific types of crime as well as distinguish fear
      by gender.

PMID- 28516854
TI  - Mother, Father, and Teacher Agreement on Victimization and Bullying in Children
      With Psychiatric Disorders.
AB  - Bullying is a significant international problem, and parent-teacher agreement on
      identifying perpetrators and victims is poor in general population studies. The
      goal of our study is to assess informant discrepancies in children with mental
      health disorders. Parents and teachers completed the Pediatric Behavior Scale as
      part of a diagnostic evaluation for 1,723 children (ages 2-16 years) referred to
      a psychiatry clinic over the past 10 years. Mother and father bullying and
      victimization ratings on the Pediatric Behavior Scale were similar, but parent
      teacher agreement was poor. Half of parents considered their child a victim,
      twice the percentage for teachers. Parents were 1.2 times more likely than
      teachers to perceive their child as a bully. Most parents reported their child
      was a victim or bully, whereas most teachers reported the children were neither.
      For both parents and teachers, victim and bully percentages for our psychiatric
      sample were twice as high as in general population studies. Clinicians should
      obtain information from multiple informants and consider that teacher report is
      likely to be lower than parent report.

PMID- 28516855
TI  - Victim Impact Statements: How Victim Social Class Affects Juror Decision Making.
AB  - Although the Supreme Court has ruled that victim impact statements (VIS) should
      be allowed at trial, the concern voiced in Payne v. Tennessee (1991) and Furman
      v. Georgia (1972) was that VIS might enable jurors to make comparative judgments
      about the worth of the victim. This study examined the effect VIS and low and
      middle socioeconomic status (SES) victims have on jurors' decisions. Mock jurors
      listened to 1 of 3 audio recordings of the sentencing phase of a capital murder
      trial (no VIS, low SES VIS, or middle SES VIS) and were asked to sentence the
      defendant to either life in prison without parole or death. Results indicated VIS
      themselves did not significantly affect mock jurors' sentencing decisions.
      However, mock jurors who heard the middle SES victim VIS were significantly more
      likely to sentence the defendant to death compared to those who heard the low SES
      victim VIS. The results suggest that the concerns of the Supreme Court were
      valid. Mock jurors were impacted by SES information in the VIS and were more
      punitive toward the defendant when he killed a higher rather than a lower SES
      person.

PMID- 28516852
TI  - Effects of olanexidine gluconate on preoperative skin preparation: an
      experimental study in cynomolgus monkeys.
AB  - PURPOSE: To determine the bactericidal efficacy of a new topical antiseptic for
      preoperative skin preparation, olanexidine gluconate (development code: OPB
      2045G), against transient or resident bacterial flora on the skin of cynomolgus
      monkeys. METHODOLOGY: After measuring baseline bacterial counts on test sites
      marked on the abdomens, we applied olanexidine, chlorhexidine or povidone-iodine.
      After 10 min (fast-acting effect) and 6 h (long-lasting effect), bacterial counts
      were measured again and log10 reductions were calculated. In addition, we
      determined the bactericidal effects on the skin contaminated with blood before or
      after applying the antiseptics. RESULTS: In the non-blood-contaminated condition,
      the mean log10 reductions of olanexidine at doses of 1-2 % were significantly
      higher than those of saline (negative control), but did not significantly differ
      from those of 0.5 % chlorhexidine and 10 % povidone-iodine at either time point.
      But olanexidine was significantly more effective at both time points than
      chlorhexidine and povidone-iodine when applied after the site was contaminated
      with blood. Olanexidine was also significantly more effective than chlorhexidine
      and as effective as or more effective than povidone-iodine at both time points
      when skin was contaminated with blood after the antiseptics were applied.
      CONCLUSION: The bactericidal effects of olanexidine were comparable to those of
      commercial antiseptics such as chlorhexidine and povidone-iodine in non-blood
      contaminated conditions. More importantly, the effect of olanexidine was hardly
      affected by blood unlike commercial antiseptics. Thus, it is considered that
      olanexidine has a favourable property for skin preparation in various types of
      surgical treatments.

PMID- 28516856
TI  - Dating Violence Perpetration: Associations With Early Maladaptive Schemas.
AB  - Violence between dating couples is a serious and prevalent problem among college
      students (Shorey, Cornelius, & Bell, 2008). Social-cognitive theories of
      aggression (e.g., Berkowitz, 1990) propose that perpetrators may have more
      maladaptive cognitive schemas that increase risk for aggression than non
      perpetrators. Thus, this study examined differences between perpetrators and non
      perpetrators of dating violence on early maladaptive schemas, which are rigidly
      held cognitive and behavioral patterns that guide how individuals encode and
      respond to stimuli in their environments (Young, Klosko, & Weishaar, 2003).
      Within a sample of female (n = 242) and male (n = 193) college students, results
      demonstrated that many early maladaptive schema domains were associated with
      psychological and physical dating violence perpetration, although mostly for
      women. In addition, the schema domain of impaired autonomy showed medium-to-large
      differences between female perpetrators and non-perpetrators, whereas the domain
      of impaired limits showed a medium-to-large difference for male perpetrators and
      non-perpetrators of physical aggression. These findings add to a growing body of
      literature on risk factors for dating violence, suggesting that early maladaptive
      schemas may be associated with individual differences in aggression risk. The
      results also further support social-cognitive models of aggressive behavior.

PMID- 28516857
TI  - Co-Occurring Cyberbullying and School Bullying Victimization and Associations
      With Mental Health Problems Among Canadian Middle and High School Students.
AB  - This study examined the associations between co-occurring cyberbullying and
      school bullying victimization with poor self-rated mental health, psychological
      distress, and suicidal ideation and attempts among 4,886 Canadian students in
      Grades 7-12 and tested whether these associations differed between middle and
      high school students. There are 12.2% of students who were victims of both
      cyberbullying and school bullying. After adjusting for covariates, victims of
      both cyberbullying and school bullying presented the highest odds of poor self
      rated mental health (odds ratio [OR] = 5.02; 95% CI [3.75, 6.74]), psychological
      distress (OR = 5.91; 95% CI [4.38, 7.96]), and suicidal ideation (OR = 6.17; 95%
      CI [4.44, 8.56]) and attempts (OR = 7.68; 95% CI [3.95, 14.93]). These
      associations were stronger among middle-school youth than their high school
      counterparts. Results suggest that victims of both cyberbullying and school
      bullying may constitute the most vulnerable group and that there is a need for
      intervention programs addressing both forms of bullying simultaneously,
      particularly among middle school students.

PMID- 28516858
TI  - Southern Women at Risk: Narratives of Familial and Social HIV Risk in Justice
      Involved U.S. Women in Alabama.
AB  - Justice-involved HIV-positive women, particularly those in the U.S. South, are a
      hidden, understudied population. Little work has explored their psychosocial
      histories in relation to their HIV risk. We conducted a content analysis of their
      life history narratives from childhood to present, via in-depth interviews with
      24 such women in 2 Alabama cities. Findings included the following: (a) In
      childhood/adolescence, consistent HIV risk factors were present, beginning with
      early sexual abuse and induction into alcohol/substance use; (b) By early
      adulthood, HIV and incarceration risks were compounded in social settings,
      through cyclical substance use, revictimization, and reoffending;

PMID- 28516859
TI  - Recombinant esterase from Corynebacterium pseudotuberculosis in DNA and subunit
      recombinant vaccines partially protects mice against challenge.
AB  - PURPOSE: We tested the efficacy of the esterase encoded by cp1002_RS09720 from
      Corynebacteriumpseudotuberculosis in recombinant subunit and DNA caseous
      lymphadenitis (CLA) vaccines. This target was predicted as one of the best CLA
      vaccine candidates by mature epitope density analysis. METHODOLOGY: Gene
      cp1002_RS09720 was cloned into two different vectors (pAE for subunit vaccine and
      pTARGET for DNA vaccine). Four groups of 15 mice each were immunized with the
      recombinant esterase rCP09720 associated with aluminium hydroxide adjuvant (G1),
      pTARGET/cp09720 DNA vaccine (G2), a naked pTARGET (G3) or PBS as a negative
      control (G4). Immunization occurred in two doses intercalated by a 21 day
      interval. Twenty-one days after the last dose administration, animals were
      challenged with a virulent C. pseudotuberculosis MIC-6 strain. RESULTS: G1 showed
      high levels of IgG1 and IgG2a on days 21 and 42 post-immunization and a
      significant level of IFN-gamma (P<0.05), suggesting a Th1 response. The
      protection levels obtained were 58.3 and 16.6 % for G1 and G2, respectively.
      CONCLUSION: The subunit vaccine composed of the recombinant esterase rCP09720 and
      Al(OH)3 is a promising antigenic formulation for use against CLA.

PMID- 28516860
TI  - Salmonella DIVA vaccine reduces disease, colonization and shedding due to
      virulent S. Typhimurium infection in swine.
AB  - PURPOSE: Non-host-adapted Salmonella serovars, including the common human food
      borne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), are
      opportunistic pathogens that can colonize food-producing animals without causing
      overt disease. Interventions against Salmonella are needed to enhance food
      safety, protect animal health and allow the differentiation of infected from
      vaccinated animals (DIVA). METHODOLOGY: An attenuated S. Typhimurium DIVA vaccine
      (BBS 866) was characterized for the protection of pigs following challenge with
      virulent S. Typhimurium. The porcine transcriptional response to BBS 866
      vaccination was evaluated. RNA-Seq analysis was used to compare gene expression
      between BBS 866 and its parent; phenotypic assays were performed to confirm
      transcriptional differences observed between the strains. RESULTS: Vaccination
      significantly reduced fever and interferon-gamma (IFNgamma) levels in swine
      challenged with virulent S. Typhimurium compared to mock-vaccinated pigs.
      Salmonella faecal shedding and gastrointestinal tissue colonization were
      significantly lower in vaccinated swine. RNA-Seq analysis comparing BBS 866 to
      its parental S. Typhimurium strain demonstrated reduced expression of the genes
      involved in cellular invasion and bacterial motility; decreased invasion of
      porcine-derived IPEC-J2 cells and swimming motility for the vaccine strain was
      consistent with the RNA-Seq analysis. Numerous membrane proteins were
      differentially expressed, which was an anticipated gene expression pattern due to
      the targeted deletion of several regulatory genes in the vaccine strain. RNA-Seq
      analysis indicated that genes involved in the porcine immune and inflammatory
      response were differentially regulated at 2 days post-vaccination compared to pre
      vaccination. CONCLUSION: Evaluation of the S. Typhimurium DIVA vaccine indicates
      that vaccination will provide both swine health and food safety benefits.

PMID- 28516861
TI  - Victim Gender, Rater Attitudes, and Rater Violence History Influence Perceptions
      of Intimate Partner Violence.
AB  - Perceptions of intimate partner violence (IPV) have been proposed to play a role
      in the stigmatization and underreporting of violence by individuals who are
      victimized by intimate partners, especially in cases that are inconsistent with
      the male-to-female IPV paradigm. We examined the independent and combined
      influences of victim and perpetrator sex, attitudes toward gender roles, and
      history of IPV perpetration on perceptions of IPV among 240 college students. We
      employed a vignette methodology to manipulate perpetrator and victim sex in a
      fully crossed design. Results indicate that violence perpetrated against males is
      perceived as less serious and more justified, and male victims are perceived to
      be more blameworthy than female victims. Traditional gender role attitudes and
      histories of IPV perpetration are associated with greater blaming of victims and
      justification of perpetrators across contexts.

PMID- 28516863
TI  - Sporadic Creutzfeldt-Jakob Disease in 2 Plasma Product Recipients, United
      Kingdom.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) has not been previously reported in
      patients with clotting disorders treated with fractionated plasma products. We
      report 2 cases of sCJD identified in the United Kingdom in patients with a
      history of extended treatment for clotting disorders; 1 patient had hemophilia B
      and the other von Willebrand disease. Both patients had been informed previously
      that they were at increased risk for variant CJD because of past treatment with
      fractionated plasma products sourced in the United Kingdom. However, both cases
      had clinical and investigative features suggestive of sCJD. This diagnosis was
      confirmed in both cases on neuropathologic and biochemical analysis of the brain.
      A causal link between the treatment with plasma products and the development of
      sCJD has not been established, and the occurrence of these cases may simply
      reflect a chance event in the context of systematic surveillance for CJD in large
      populations.

PMID- 28516862
TI  - Non-essential MCM-related proteins mediate a response to DNA damage in the
      archaeon Methanococcus maripaludis.
AB  - The single minichromosome maintenance (MCM) protein found in most archaea has
      been widely studied as a simplified model for the MCM complex that forms the
      catalytic core of the eukaryotic replicative helicase. Organisms of the order
      Methanococcales are unusual in possessing multiple MCM homologues. The
      Methanococcus maripaludis S2 genome encodes four MCM homologues, McmA-McmD. DNA
      helicase assays reveal that the unwinding activity of the three MCM-like proteins
      is highly variable despite sequence similarities and suggests additional motifs
      that influence MCM function are yet to be identified. While the gene encoding
      McmA could not be deleted, strains harbouring individual deletions of genes
      encoding each of the other MCMs display phenotypes consistent with these proteins
      modulating DNA damage responses. M. maripaludis S2 is the first archaeon in which
      MCM proteins have been shown to influence the DNA damage response.

PMID- 28516864
TI  - Genomic Analysis of Salmonella enterica Serovar Typhimurium DT160 Associated with
      a 14-Year Outbreak, New Zealand, 1998-2012.
AB  - During 1998-2012, an extended outbreak of Salmonella enterica serovar Typhimurium
      definitive type 160 (DT160) affected >3,000 humans and killed wild birds in New
      Zealand. However, the relationship between DT160 within these 2 host groups and
      the origin of the outbreak are unknown. Whole-genome sequencing was used to
      compare 109 Salmonella Typhimurium DT160 isolates from sources throughout New
      Zealand. We provide evidence that DT160 was introduced into New Zealand around
      1997 and rapidly propagated throughout the country, becoming more genetically
      diverse over time. The genetic heterogeneity was evenly distributed across
      multiple predicted functional protein groups, and we found no evidence of host
      group differentiation between isolates collected from human, poultry, bovid, and
      wild bird sources, indicating ongoing transmission between these host groups. Our
      findings demonstrate how a comparative genomic approach can be used to gain
      insight into outbreaks, disease transmission, and the evolution of a multihost
      pathogen after a probable point-source introduction.

PMID- 28516865
TI  - Hospital Outbreaks of Middle East Respiratory Syndrome, Daejeon, South Korea,
      2015.
AB  - From May through July 2015, a total of 26 cases of Middle East Respiratory
      Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1
      index case and 25 new cases. We examined the epidemiologic features of these
      cases and found an estimated median incubation period of 6.1 days (8.8 days in
      hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in
      hospital A and 3.0% in hospital B), and the attack rates among inpatients and
      caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case
      fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of
      cohort quarantine may have played a role in preventing community spread, but
      additional transmission occurred among members of the hospital cohort quarantined
      together. Caregivers may have contributed in part to the transmission.

PMID- 28516866
TI  - Invasive Serotype 35B Pneumococci Including an Expanding Serotype Switch Lineage,
      United States, 2015-2016.
AB  - We used whole-genome sequencing to characterize 199 nonvaccine serotype 35B
      pneumococcal strains that caused invasive pneumococcal disease (IPD) in the
      United States during 2015-2016 and related these findings to previous serotype
      35B IPD data obtained by Active Bacterial Core surveillance. Penicillin
      nonsusceptible 35B IPD increased during post-pneumococcal 7-valent conjugate
      vaccine years (2001-2009) and increased further after implementation of
      pneumococcal 13-valent conjugate vaccine in 2010. This increase was caused
      primarily by the 35B/sequence type (ST) 558 lineage. 35B/ST558 and vaccine
      serotype 9V/ST156 lineages were implicated as cps35B donor and recipient,
      respectively, for a single capsular switch event that generated emergent
      35B/ST156 progeny in 6 states during 2015-2016. Three additional capsular switch
      35B variants were identified, 2 of which also involved 35B/ST558 as cps35B donor.
      Spread of 35B/ST156 is of concern in view of past global predominance of
      pathogenic ST156 vaccine serotype strains. Protection against serotype 35B should
      be considered in next-generation pneumococcal vaccines.

PMID- 28516867
TI  - The link between Proteus mirabilis, environmental factors and autoantibodies in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a relatively common and potentially disabling immune
      mediated inflammatory systemic disease, predominantly affecting women and
      characterised by multiple small joint arthritis. Extensive data supports the
      roles of genetic, environmental and microbial factors in the triggering and
      development of this disease. Proteus mirabilis is considered as the main
      microbial culprit in the causation of RA. The evidence for the role of these
      microbes in RA and their links with commonly associated autoantibodies such as
      rheumatoid factors and anti-citrullinated peptide antibodies have been elucidated
      together with their relations with some of the non-microbial environmental
      factors which have been implicated in the aetiopathogenesis of RA. The most
      likely mechanism in the development of RA is "molecular mimicry" where Proteus
      antigens were found to share homologous sequences, which cross-react with certain
      self-antigens present in synovial tissues. This could raise possibilities for
      implementing a new therapeutic strategy in the treatment of RA.

PMID- 28516868
TI  - Predicting responses in patients with rheumatoid arthritis to disease-modifying
      agents using baseline clinical data.
AB  - OBJECTIVES: The optimal treatment for active rheumatoid arthritis (RA) is
      unresolved, particularly in early RA. We used data from an observational cohort
      to develop the simple predictor algorithm and evaluated its application in two
      completed clinical trials in early and established RA. We assessed whether using
      a simple algorithm can identify patients who have persisting active disease
      despite treatment with disease-modifying drugs (DMARDs). We also examined if
      patients who have lower likelihoods of persisting active RA are likely to benefit
      from intensive treatment. METHODS: We developed a simple predictive score for
      persisting disease activity using conventional clinical assessments in an
      observational cohort of patients with early RA (ERAN). It was tested in two
      trials in early (CARDERA) and established (TACIT) RA. Persistent disease activity
      was defined as disease activity score for 28 joints (DAS28) >3.2 at both 6 and 12
      months. RESULTS: Regression modelling identified three main predictors of
      persisting active disease in ERAN; tender joint counts, health assessment
      questionnaire (HAQ) scores and ESR. We dichotomised these predictors (>=6 tender
      joint counts, >=1.0 HAQ >=20 mm/h ESR) in a four-point prediction score. This
      simple prediction score predicted persisting active disease in the ERAN cohort
      and both CARDERA and TACIT trials. Patients with high scores were more likely to
      have persistently active disease at 6 and 12 months. The relationship was weaker
      in TACIT because no patients were without any predictive factors. CONCLUSIONS:
      Combining tender joint counts, ESR and HAQ in a simple predictive score
      prospectively identifies patients with higher risks of persistent disease
      activity over the next 12 months. More patients with all three risk factors had
      persistent active disease than those with none or one risk factor.

PMID- 28516869
TI  - Recommendations for infectious disease screening in migrants to Western Europe
      with inflammatory arthropathies before starting biologic agents. Results from a
      multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI)
      facing the largest impact of the flow of migrants today.
AB  - OBJECTIVES: Inflammatory arthritis needs infectious disease screening before
      starting a biologic agent, however, few data are known about migrant patients,
      who represent a peculiar population which requires a multidisciplinary approach
      among international health specialists and should also be considered by health
      authorities. For this reason, the Italian and Spanish Societies of Rheumatology
      (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a
      multidisciplinary task force in order to produce specific recommendations about
      screening and advices to be considered in migrant patients with inflammatory
      arthritis candidate to receive biological therapy, according to their
      geographical origin. METHODS: The experts provided a prioritised list of research
      questions and the eligible spectrum of inflammatory arthritis, biologic drugs and
      infectious disease were defined in order to perform a systematic literature
      review. A search was made in Medline, Embase and Cochrane library, updated to
      March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are
      already considered in national and international recommendations, were not
      included. The strength of each recommendation was determined. RESULTS: The task
      force members agreed on 7 overarching principles. The risk of reactivation of
      selected potentially latent infectious disease was addressed in migrants with
      inflammatory arthritis candidates for biologics was considered and 15 potentially
      relevant infections were identified. CONCLUSIONS: Fifteen disease-specific
      recommendations were formulated on the basis of high level of agreement among the
      experts panel.

PMID- 28516870
TI  - The relevance of cluster analyses to stratify systemic lupus erythematosus:
      increased mortality with heavier treatment.

PMID- 28516871
TI  - Diagnosis of catastrophic anti-phospholipid syndrome in a patient tested negative
      for conventional tests.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of APS,
      characterised by clinical evidence of multiple organ involvement developing over
      a very short period of time, histopathological evidence of multiple small vessel
      occlusions and laboratory confirmation of the presence of aPL (lupus
      anticoagulant and/or anticardiolipin antibodies and/or anti-Beta2-glcyoprotein I
      antibodies). Here we report a case of a 39-year-old woman patient who developed a
      CAPS which was negative to the conventional aPL but positive for aPL in thin
      layer chromatography immunostaining and vimentin/cardiolipin antibodies by ELISA
      test. The patient was treated with high doses of glucocorticoids, intravenous
      immunoglobulins plasma exchange and immunoadsorbent apheresis with a significant
      improvement of the ischaemic lesions of the hands even though the necrosis of the
      feet progressively worsened. As a result, the patient underwent partial surgical
      amputation of the feet. To our knowledge, this is the first ever reported case of
      CAPS diagnosed by means of thin layer chromatography immunostaining and
      vimentin/cardiolipin antibody ELISA test.

PMID- 28516872
TI  - Glucocorticoid-sparing effect of first-year anti-TNFalpha treatment in rheumatoid
      arthritis (CORPUS Cohort).
AB  - OBJECTIVES: Anti-TNFalpha agents are indicated in selected patients with
      rheumatoid arthritis (RA) who respond inadequately to methotrexate and
      particularly when glucocorticoids are mandatory. We evaluated whether a
      glucocorticoid-sparing effect occurred during the first year of anti-TNF-alpha
      therapy. METHODS: Between 2007 and 2009, the French multicentre, longitudinal,
      prospective, observational, population-based CORPUS cohort included biologic
      naive patients with inflammatory joint disease. Patients with active RA treated
      with glucocorticoids were included. Patients who received at least one anti
      TNFalpha injection during follow-up were compared to anti-TNF-alpha non-users.
      RESULTS: Among the 205 patients, 76.1% were women, mean disease duration was
      7.7+/-8.3 years, mean DAS28 was 5.2+/-1.3, mean follow-up was 13.1+/-2.8 months,
      and mean prednisone dose was 9.9+/-9.6 mg/day. The 75 (36.6%) anti-TNF-alpha
      recipients were younger, had a longer RA duration, more often tested positive for
      rheumatoid factor and anti-citrullinated peptide antibody, more often received
      previous DMARDs, received a higher methotrexate dosage, had fewer intra-articular
      glucocorticoid injections at baseline and were more often followed by hospital
      practitioners than non-recipients. Mean prednisone dosage decreased from 11.8+/
      12.7 to 5.9+/-9.7 mg/day in recipients and from 8.7+/-7.1 to 5.0+/-4.4 mg/day in
      non-recipients. Prednisone was stopped more often among recipients (21/59, 35.6%)
      than among non-recipients (16/94, 17.0%) (p=0.01). By multivariate analysis,
      factors independently associated with lower prednisone requirements were baseline
      daily prednisone dosage, a CRP >10 mg/l and not to be followed by an office-based
      practitioner. CONCLUSIONS: This study showed a significantly higher
      glucocorticoid discontinuation rate among anti-TNF-alpha recipients than among
      non-recipients. However, the glucocorticoid-sparing effect was small and not
      observed by multivariate analysis.

PMID- 28516873
TI  - About the AIRTRIP randomised clinical trial: comments on the article by Brucato
      et al.

PMID- 28516875
TI  - Reply to: Moyamoya disease and systemic sclerosis (MoSys syndrome): a combination
      of two rare entities: comment to the authors.

PMID- 28516874
TI  - Long-term effects of interleukin-17A inhibition with secukinumab in active
      ankylosing spondylitis: 3-year efficacy and safety results from an extension of
      the Phase 3 MEASURE 1 trial.
AB  - OBJECTIVES: Secukinumab, a fully human anti-IL-17A monoclonal antibody, provided
      rapid and sustained improvements in signs and symptoms of ankylosing spondylitis
      (AS) over 2 years in the Phase 3 MEASURE 1 trial. Here, we report efficacy and
      safety after 3 years of treatment. METHODS: AS subjects completing 2 years of
      treatment every 4 weeks with subcutaneous secukinumab 150 or 75 mg (following
      intravenous loading or initial placebo treatment to 16/24 weeks) entered a
      separate 3-year extension study (NCT01863732). Assessments included ASAS20/40,
      ASAS5/6, BASDAI, BASDAI 50, BASFI, BASMI, SF-36 physical component summary, ASAS
      partial remission and ASDAS-CRP. Results were also analysed by prior anti-TNF
      treatment status. RESULTS: Among 290 subjects completing the core trial, 274
      entered the extension study, with 260 subjects (94.9%) completing 156 weeks of
      treatment. ASAS20/40 response (observed) was 80.2%/61.6% in the IV->150 mg group
      and 75.5%/50.0% in the IV->75 mg group after 156 weeks. Sustained improvements
      were also seen in BASDAI, BASFI, BASMI and across all other endpoints regardless
      of previous exposure to anti-TNF agents. Mean secukinumab exposure was 964.3 days
      (137.8 weeks). Discontinuation rates were low, and secukinumab had a favourable
      safety profile, consistent with previous reports. Exposure-adjusted incidence
      rates for serious infections, Candida infections, Crohn's disease, ulcerative
      colitis, malignant/unspecified tumours, and adjudicated major adverse cardiac
      events were 1.1, 0.4, 0.5, 0.1, 0.5 and 0.7 per 100 subject-years, respectively.
      CONCLUSIONS: Secukinumab provided sustained efficacy in signs, symptoms and
      physical function in subjects with AS over 3 years. No new safety signals were
      observed.

PMID- 28516876
TI  - Multiple testing in the 'Canakinumab in atherosclerosis' trial: correction
      required?

PMID- 28516877
TI  - Validity of the Workers Productivity and Activity Impairment Questionnaire:
      Specific Health Problem (WPAI:SHP) in patients with systemic sclerosis.
AB  - OBJECTIVES: To evaluate the construct validity of the Workers Productivity and
      Impairment Activity Index: Specific Health Problem (WPAI:SHP) in Australian
      systemic sclerosis (SSc) patients. METHODS: SSc patients, identified through the
      Australian Scleroderma Cohort Study database, completed the WPAI:SHP and a
      quality of life instrument (PROMIS-29) cross-sectionally. The construct validity
      of the WPAI:SHP was assessed by the correlations between the WPAI:SHP and a range
      of SSc health states. Non-parametric correlation, including Spearman's
      correlation (rho), was used to test the validity of WPAI:SHP and ability to
      distinguish between different health states. RESULTS: A total of 476 completed
      questionnaires was returned, equating to a response rate of 63.7%. Among those
      under 65 years of age, 155 patients (55.2%) were in paid employment. Employed
      patients had a mean (+/- SD) age of 56.5 (9.8) years and were predominantly
      female (87.3%) with limited disease subtype (75.6%). The WPAI:SHP showed
      construct validity based on moderate to strong correlations with health status as
      assessed by a range of health outcome measures including disease activity
      (rho=0.34-0.39, p=0.001), physical function (rho=0.55-0.62, p=0.001), disease
      severity(rho=0.55-0.62, p=0.001), fatigue (rho= 0.62-0.63, p=0.001), pain
      (rho=0.68-0.71, p=0.001), and breathlessness (rho=0.39-0.46, p=0.001).
      Furthermore, according to the effect size, the WPAI:SHP scores have a large
      discriminative ability (d=1.26-1.47) for distinguishing SSc patients with
      different health outcomes. CONCLUSIONS: The WPAI is a valid questionnaire for
      assessing impairments in paid employment and social activities in SSc patients,
      and for measuring the relative differences between SSc patients with varying
      health states.

PMID- 28516878
TI  - High incidence of vertebral osteoporotic fracture within the first year after
      liver transplantation.
AB  - OBJECTIVES: Bone loss is a complication for patients with liver diseases and
      after transplantation, which results in increased fracture risk. The aim of this
      study was to determine the incidence of osteoporotic vertebral fractures
      following liver transplantation. METHODS: We performed a prospective study of
      patients who were awaiting liver transplantation. Patients were seen at baseline
      (visit 1) and one year after transplantation (visit 2). At each visit, risk
      factors of osteoporosis were collected, biochemical tests were performed and bone
      mineral density with Vertebral Fracture Assessment was assessed. RESULTS: One
      hundred and fifteen patients were in the pre-transplant group and 33 patients
      were in the post-transplant group. In the pre-transplant group, the prevalence of
      vertebral fractures was 23.5%. The prevalence of densitometric osteoporosis was
      higher at the lumbar spine than at the femoral neck. In the post-transplant
      group, the prevalence of vertebral fractures at visit 1 and visit 2 was 33.3% and
      60.6% respectively with an incidence of 23.1 fractures per 100 patient-years.
      CONCLUSIONS: Bone fragility was highly prevalent before transplantation and
      worsens one year after transplantation. Bone status should be evaluated in
      patients with liver diseases before transplantation to identify patients at high
      risk of fracture and help clinicians to prescribe appropriate preventive care.

PMID- 28516879
TI  - Comparison of efficacy of first- versus second-line adalimumab in patients with
      rheumatoid arthritis: experience of the Italian biologics registries.
AB  - OBJECTIVES: Targeted drugs against key pathogenetic molecules such as TNF-alpha
      have significantly improved outcomes in rheumatoid arthritis (RA). They are
      widely used in clinical practice and drug registries give us information to
      support their use. Adalimumab (ADA) is able to induce a comprehensive disease
      control in RA by achieving clinical, functional and radiographic control.
      METHODS: By interrogating 2 Italian registries, LORHEN and GISEA, we analysed the
      efficacy of ADA in first- or second-line in a total of 2262 RA patients. RESULTS:
      Patients in 1st line were significantly older, with lower disease activity and
      HAQ scores compared to 2nd line. In 1st line, rates of DAS28-remission (DAS28rem)
      at 2 years were 34.4% while 26.5% in 2nd line (p=0.038). A normal HAQ score
      (HAQ<=0.5) was achieved in 53.5% after 2 years in 1st line versus 30.1% in 2nd
      (p<0.0001). DAS28rem+HAQ<=0.5, a combined parameter that we defined global
      clinical disease control, was reached in 20.7% in 1st line versus 13.3% in 2nd
      (p<0.01). Five-year-survival on therapy was higher for patients in 1st line
      (45.6% vs. 33.2%, p<0.0001). Discontinuation due to lack of efficacy was lower in
      1st line (37.4 vs. 54.4%, p<0.0001). Rates of adverse events were similar.
      CONCLUSIONS: Responses in 1st line are generally significantly better than after
      a first anti-TNF-alpha failure but patients in 2nd line have a worse clinical and
      functional profile. A global disease control with clinical and functional
      remission is an achievable target in both lines.

PMID- 28516880
TI  - Abatacept therapy reduces CD28+CXCR5+ follicular helper-like T cells in patients
      with rheumatoid arthritis.
AB  - OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases
      of rheumatoid arthritis (RA) are still unknown. The goal of the study was to
      determine the pathogenicity of T cells and the predictors of therapeutic effects
      of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RA patients
      via flow cytometry. The correlation of the phenotypes of CD4+ T cells with
      clinical disease activity and change in CD4+ T cell subsets at baseline and 24
      weeks after ABT treatment were evaluated. RESULTS: RA patients showed an increase
      in the proportion of CD28- cells among CD4+ cells, which was significantly high
      in patients who had not achieved remission after ABT therapy. The proportions of
      CD4+CXCR5+ T follicular helper-like (Tfh-like) cells increased in RA patients
      compared to healthy donors. The proportions of Tfh-like cells among CD4+CD28+
      cells were significantly higher than those among CD4+CD28- cells. The proportion
      of Tfh-like cells was higher in anti-cyclic citrullinated peptide antibody (ACPA)
      positive patients. By contrast, the proportions of CD4+CXCR3+ T helper 1-like
      (Th1-like) cells and effector memory phase T cells among CD4+CD28- cells were
      significantly higher than those among CD4+CD28+ cells, and the proportion of
      these cells did not correlate with disease activity. After ABT therapy, the
      proportion of Tfh-like cells among CD4+CD28+ cells was significantly reduced.
      CONCLUSIONS: These results imply that CD4+ CD28+ Tfh-like cells could possibly be
      the targets of ABT. Conversely, CD4+ CD28- cells may be a potential predictor of
      treatment resistance.

PMID- 28516882
TI  - Interstitial lung disease is associated to infections of lower respiratory tract
      in immunocompromised rheumatoid arthritis patients.

PMID- 28516881
TI  - Exploring the remission concept in rheumatoid arthritis with patients and
      rheumatologists: time for a new approach?
AB  - OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and to
      compare remission definitions and related concepts between rheumatologists and
      patients with the purpose of identifying similarities and disparities to
      comprehend the different perspectives of the disease. METHODS: This was a
      qualitative study of discourse and content analysis through focus groups,
      conducted from February to March 2016. Four focus groups were set up, each one
      with different interests: rheumatologists involved in basic research (BR),
      rheumatologists with high specialisation in imaging techniques (IR), clinical
      rheumatologists (CR), and patients (PA). RESULTS: There is no consensus in a
      remission definition in RA; differences exist between-groups, rheumatologists and
      patients value remission differently, and there are discrepancies within the
      group of rheumatologists. Rheumatologists highlight quantifiable objective
      parameters, in contrast, patients did not consider objective measures as the best
      instruments, and they prefer subjective measures of remission. The data confirmed
      the existence of two sources of knowledge of the disease, technical (physicians)
      and experiential (patients). These sources of knowledge should concur in order to
      establish new remission criteria well-adjusted to reality. CONCLUSIONS: The lack
      of consensus between key groups implicated in defining remission and remission
      criteria suggests a new strategy for its operational definition. Our group
      proposes that subjects with a balance between experiential and technical
      knowledge, should be the ones in charge of this assignment.

PMID- 28516883
TI  - Sarcoidosis and tocilizumab: is there a link?

PMID- 28516885
TI  - RAPID3 correlates with ESSPRI and other patient-reported outcomes in patients
      with primary Sjogren's syndrome.

PMID- 28516884
TI  - Patient participation in patient-reported outcome instrument development in
      systemic sclerosis.
AB  - OBJECTIVES: The patient perspective captured using Patient-Reported Outcome (PRO)
      instruments provide insight into the patient condition not always captured by
      physician-derived assessment tools. Target patient population involvement is an
      essential component of PRO instrument development. We have reviewed the level of
      patient involvement in the development of PRO instruments used in the assessment
      of systemic sclerosis (SSc). METHODS: A comprehensive literature review was
      undertaken to identify studies reporting PRO instruments in SSc. Studies were
      assessed to establish whether the PRO instruments had been developed specifically
      for SSc or adopted from other disease areas. Studies reporting PRO instruments
      specific for SSc were scrutinised for evidence of target patient population
      involvement in the development of the instrument. RESULTS: A total of 58 PRO
      instruments that have been used in SSc research were identified. Twelve (21%) of
      these were developed specifically for outcome assessment within SSc populations.
      Of these, 5 (42%) had not reported any patient involvement in the development
      phase of the instrument. Five SSc PRO instruments (42%) involved target patient
      population in the domain/item generation stage. Four (33%) of SSc PRO instruments
      had undertaken cognitive interviewing to ensure item wording adequately captured
      the intended conceptual framework. CONCLUSIONS: The majority of PRO instruments
      used to assess SSc have not involved significant target patient involvement in
      their development. By involving patients in the development of novel PRO
      instruments in SSc, we can ensure such instruments adequately capture the
      experiences most relevant to our patients.

PMID- 28516886
TI  - Patterns of tocilizumab use, effectiveness and safety in patients with rheumatoid
      arthritis: core data results from a set of multinational observational studies.
AB  - OBJECTIVES: To observe patients with rheumatoid arthritis (RA) treated with the
      interleukin-6 receptor-alpha inhibitor tocilizumab (TCZ) in routine clinical
      practice. METHODS: Data on concomitant medications, effectiveness and safety were
      pooled from independent, multinational studies in patients with RA initiating
      intravenous TCZ according to local label recommendations observed in routine
      practice for 6 months. Patients were grouped by TCZ monotherapy or combination
      therapy with conventional synthetic disease-modifying anti-rheumatic drugs
      (csDMARDs). The primary endpoint was the proportion of patients receiving TCZ
      after 6 months. RESULTS: Of 1336 patients enrolled, 506 (37.9%) received TCZ
      monotherapy and 830 (62.1%) received combination therapy. Kaplan-Meier analysis
      estimated that 80% (95% CI, 76%-83%) of monotherapy and 87% (95% CI, 84%-89%) of
      combination therapy patients continued to receive TCZ at 6 months (log-rank
      p<0.001). During the observation period, TCZ was discontinued by 113 (22.3%)
      monotherapy patients and 116 (14.0%) patients on combination therapy. The mean
      prednisone-equivalent oral corticosteroid dose was 8.4 mg/day for monotherapy and
      combination therapy patients at baseline and 7.7 and 7.6 mg/day, respectively, at
      month 6. Adverse events or laboratory abnormalities requiring TCZ dose
      modification were reported for 66 (13.0%) monotherapy and 130 (15.7%) combination
      therapy patients. Effectiveness at 6 months was similar between groups; mean (SD)
      change from baseline in Clinical Disease Activity Index (CDAI) was -20.3 (14.18)
      for monotherapy and -22.3 (16.09) for combination therapy (p=0.7347).
      CONCLUSIONS: In routine clinical practice, 38% of patients received TCZ as
      monotherapy. Persistence on monotherapy or in combination therapy with csDMARDs
      was high, with a slight trend towards a higher rate with combination therapy, and
      effectiveness was similar between groups.

PMID- 28516888
TI  - One biopsy, two diagnoses: statin-induced autoimmune myopathy in combination with
      extranodal marginal zone lymphoma.

PMID- 28516887
TI  - Tenosynovitis in rheumatoid arthritis patients on biologic treatment: involvement
      and sensitivity to change compared to joint inflammation.
AB  - OBJECTIVES: Extensor carpi ulnaris (ECU) and tibialis posterior (TP) tendons are
      often involved in RA and the present aim was to examine by ultrasound (US) their
      frequency of inflammation and sensitivity to change in comparison to joint
      involvement as well as clinical examinations. METHODS: US, clinical and
      laboratory assessments were performed when starting biologic DMARD (bDMARD) and
      after 1, 2, 3, 6 and 12 months including bilateral grey-scale (GS) and power
      Doppler (PD) semi-quantitatively (0-3) scoring of ECU and TP tendons and 18
      joints. Changes from baseline to follow-up were explored by Wilcoxon signed rank
      test, associations by Spearman's rank correlations and responses to treatment by
      Standardised Response Means (SRMs). RESULTS: 157 patients (mean age/disease
      duration 52.4/10.2 years) were included. ECU/TP tenosynovitis was frequent
      (baseline GS/PD pathology in 76/50% of patients) and more prevalent than
      synovitis of large joints. Tenosynovitis sum scores decreased throughout follow
      up (p<0.001) and was correlated with US of joints (0.51-0.62), clinical
      assessments (swollen joint count (0.29-0.41) and assessor's global (0.35-0.46))
      (p<0.001). US tenosynovitis sum scores had SRMs comparable to joint, clinical and
      laboratory assessments. CONCLUSIONS: Tenosynovitis in ECU/TP tendons were
      frequent, sensitive to change during bDMARD treatment and were associated to
      joint and clinical assessments. This supports the argument for tenosynovitis to
      be included in US scores of RA patients, while further studies should explore
      which tendons.

PMID- 28516889
TI  - An update on the animal models in hyperuricaemia research.
AB  - Hyperuricaemia is a metabolic disease caused by purine metabolic abnormalities,
      mainly due to the increased formation or reduced excretion of uric acid. In
      recent years, it has been proved that hyperuricaemia is an important risk factor
      for chronic kidney disease (CKD) and cardiovascular disease, and it also takes
      part in the pathophysiology of metabolic syndrome. In addition, more attention
      has been concentrated on the pathogenesis or treatment of hyperuricaemia. Since
      establishing an animal model on hyperuricaemia is the foundation for further
      researches, several methods to establish the hyperuricaemia model have been
      developed. In this article, remarkable progress on the modelling approach are
      summarised, and a comparison study on different methods of developing
      hyperuricaemia animal models was conducted.

PMID- 28516891
TI  - Proposed Bose-Einstein condensation of magnons in nanostructured films of Gd at
      low temperature and its manifestations in electrical resistivity and
      magnetoresistance.
AB  - In this paper we report the observation of a proposed Bose-Einstein condensation
      (BEC) of magnons in a temperature range of around 15-20 K in nanostructured films
      of Gd with grain sizes that are much larger than the size range where
      superparamagentism is expected. The observation was carried out using magnetic as
      well as high precision resistivity and magnetoresistance (MR) measurements
      performed to low temperatures. We observe that the experimental observations
      depend crucially on one parameter, namely softening of the spin wave stiffness
      parameter D at BEC and the resistivity as well as MR can be related
      quantitatively to magnetic measurements through the temperature variation of the
      constant D in the vicinity of the transition. This paper establishes that the BEC
      reported before in nanocrystalline Gd can be extended to a somewhat larger size
      range.

PMID- 28516890
TI  - Tocilizumab in the treatment of patients with rheumatoid arthritis in real
      clinical practice: results of an Italian observational study.
AB  - OBJECTIVES: To describe the effectiveness and safety of tocilizumab (TCZ), an
      interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid
      arthritis (RA) recruited in clinical practice. METHODS: TRUST was an
      observational study in RA patients who started treatment with TCZ in the 6 months
      prior to site activation and were still on treatment at start of study; patients
      were followed up to 12 months after the first TCZ infusion. RESULTS: 322 RA
      patients were enrolled in 59 Italian centres (mean age: 55.8 years; mean disease
      duration: 120.5 months; baseline DAS28: 5.3). After 6 months of TCZ treatment,
      patients achieving low disease activity (DAS28 <=3.2; 57.52%) or disease
      remission (DAS28 <2.6; 38.05%) were 216 out of 226 patients with available DAS28
      (p<0.001). No statistically significant differences were found in mean DAS28 and
      HAQ score changes from baseline (start of TCZ treatment) to study end between
      patients previously inadequately responding to disease-modifyinganti-rheumatic
      drugs (DMARD-IR) or to DMARDs plus tumour necrosis factor inhibitors (DMARD +TNFi
      IR): both patient populations responded to TCZ. A statistically significant
      decrease in mean VAS Fatigue score (48.4 vs. 34.7; p=0.0025) at month 6 was
      observed. In patients treated with TCZ as monotherapy (32.61%), DAS28, VAS
      fatigue and HAQ scores decreased from baseline to any post-baseline time point.
      Overall, 62 patients (19.3%) prematurely discontinued TCZ treatment, 24 (7.5%)
      for safety reasons. Drug-related adverse events occurred in 92 patients (28.6%)
      (mostly 3 hypercholesterolaemia and leucopenia) and drug-related serious adverse
      events in 11 patients (3.4%). CONCLUSIONS: This study confirms the good
      effectiveness and safety profile of TCZ in real life RA patient care.

PMID- 28516892
TI  - Current situations and discussions in Japan in relation to the new occupational
      equivalent dose limit for the lens of the eye.
AB  - Since the International Commission on Radiological Protection recommended
      reducing the occupational equivalent dose limit for the lens of the eye in 2011,
      there have been extensive discussions in various countries. This paper reviews
      the current situation in radiation protection of the ocular lens and the
      discussions on the potential impact of the new lens dose limit in Japan. Topics
      include historical changes to the lens dose limit, the current situation with
      occupational lens exposures (e.g., in medical workers, nuclear workers, and
      Fukushima nuclear power plant workers) and measurements, and the current status
      of biological studies and epidemiological studies on radiation cataracts. Our
      focus is on the situation in Japan, but we believe such information sharing will
      be useful in many other countries.

PMID- 28516894
TI  - Toy model for uncommon spin-orbit-driven spin-torque terms.
AB  - A toy model combining the angular magneto electric (AME) coupling Hamitonian
      (Mondal et al 2015 Phys. Rev. B 92 100402) with long-range magnetic dipolar
      interactions is used to investigate spin-torque phenomena in a magnetic spin
      valve. It is found that such model (1) gives rise to spin-torque expressions that
      are analogous in form to those of the common spin-transfer torques; but also (2)
      predicts additional spin-torque terms, which are generated by an electrical
      current oriented along unconventional, in-plane directions. The magnitude of the
      AME induced terms is estimated and the conditions under which they may contribute
      significantly are explored.

PMID- 28516893
TI  - Design of electrohydrodynamic sprayed polyethylene glycol hydrogel microspheres
      for cell encapsulation.
AB  - Electrohydrodynamic spraying (EHS) has recently gained popularity for
      microencapsulation of cells for applications in cell delivery and tissue
      engineering. Some of the polymers compatible with EHS are alginate, chitosan, and
      other similar natural polymers, which are subject to ionotropic or physical
      gelation. It is desirable to further extend the use of the EHS technique beyond
      such polymers for wider biofabrication applications. Here, building upon our
      previous work of making PEG microspheres via EHS, we utilized the principles of
      EHS to fabricate cell-laden polyethylene glycol (PEG) hydrogel microspheres. The
      gelation of PEG hydrogel microspheres was achieved by forming covalent crosslinks
      between multiarm PEG acrylate and dithiol crosslinkers via Michael-type addition.
      We conducted a detailed investigation of the critical parameters of EHS, such as
      the applied voltage, inner needle diameter (i.d. needle), and flow rate, to
      obtain PEG microspheres with high cell viability and tightly-controlled diameters
      in the range of 70-300 MUm. The polydispersity of cell-laden PEG hydrogel
      microspheres as measured by % coefficient of variation was between 6% and 23% for
      all conditions tested. We established that our method was compatible with
      different cell types and that all tested cell types could be encapsulated at high
      densities of 106-109 and >=90% encapsulation efficiency. We observed cell
      aggregation within the hydrogel microspheres at applied voltage >5 kV. Since PEG
      is a synthetic polymer devoid of cell attachment sites, we could overcome this
      limitation by tethering Arg-Gly-Asp-Ser (RGDS) peptide to the PEG hydrogel
      microspheres; upon RGDS tethering, we observed uniform cell dispersion. The
      microencapsulated cells could be cultured in the PEG hydrogel microspheres of
      different sizes for up to one week without significant loss in cell viability. In
      conclusion, the EHS technique developed here could be used to generate cell-laden
      PEG hydrogel microspheres of controlled sizes for potential applications in cell
      delivery and organoid cultures.

PMID- 28516895
TI  - Effect of magnetic field on electronic transport in a bilayer graphene nanomesh.
AB  - We report on the observation of an unexpected sudden increase of resistance in
      bilayer graphene nanomesh (GNM) in the temperature range 270 ~ 300 K that is
      strongly dependent on the magnetic field strength. We conjecture that the sharp
      increase in resistance originates from ripple scattering as induced by substrate
      roughness. The observed result is evidence of extrinsic corrugation in bilayer
      GNM as an additional scattering source that contributes to significant
      resistance. The observed weak localization in the GNM indicates intervalley
      scattering induced by lattice defects acts as resonant scatterers attribute to
      the high D peak. Magnetotransport measurement strongly supports that the charge
      inhomogeneity related to the intrinsic disorder in bilayer GNM and the positive
      magnetoresistance shows a linear behavior with magnetic field strength.
      Potentially, the observed phenomena, therefore, point to a clear pathway towards
      practical application of bilayer GNM and to the design of a graphene magnetic
      sensor that can be manipulated by a magnetic field and a new generation of
      spintronics.

PMID- 28516896
TI  - Direct and indirect light emissions from layered ReS2-x Se x (0 <= x <= 2).
AB  - ReS2 and ReSe2 have recently been enthusiastically studied owing to the specific
      in-plane electrical, optical and structural anisotropy caused by their distorted
      one-layer trigonal (1 T) phase, whereas other traditional transition-metal
      dichalcogenides (TMDCs, e.g. MoS2 and WSe2) have a hexagonal structure. Because
      of this special property, more and versatile nano-electronics and nano
      optoelectronics devices can be developed. In this work, 2D materials in the
      series ReS2-x Se x (0 <= x <= 2) have been successfully grown by the method of
      chemical vapor transport. The direct and indirect resonant emissions of the
      complete series of layers can be simultaneously detected by polarized micro
      photoluminescence (MUPL) spectroscopy when the thickness of the ReS2-x Se x is
      greater than ~70 nm. When it is less than 70 nm, only three direct excitonic
      emissions-E 1ex, E 2ex and E Sex-are detected. For the thick (bulk) ReS2-x Se x ,
      more stacking of the ReX2 monolayers even flattens and shifts the valence-band
      maximum from Gamma to the other K- or M-related points, thus leading to the
      coexistence of direct and indirect resonant light emissions from the c-plane
      ReX2. The transmittance absorption edge of each bulk ReX2 (a few microns thick)
      usually has a lower energy than those of the direct E 1ex and E 2ex excitonic
      emissions to form indirect absorption. The coexistence of direct and indirect
      emissions in ReX2 is a unique characteristic of a 2D layered semiconductor
      possessing triclinic low symmetry.

PMID- 28516897
TI  - Intrinsic valley polarization of magnetic VSe2 monolayers.
AB  - Intrinsic valley polarization can be obtained in VSe2 monolayers with broken
      inversion symmetry and time reversal symmetry. First-principles investigations
      reveal that the magnitude of the valley splitting in magnetic VSe2 induced by
      spin-orbit coupling reaches as high as 78.2 meV and can be linearly tuned by
      biaxial strain. Besides conventional polarized light, hole doping or illumination
      with light of proper frequency can offer effective routes to realize valley
      polarization. Moreover, spin-orbit coupling in monolayer VSe2 breaks not only the
      valley degeneracy but also the three-fold rotational symmetry in band structure.
      The intrinsic and tunable valley splitting and the breaking of optical isotropy
      bring additional benefits to valleytronic and optoelectronic applications.

PMID- 28516898
TI  - Structural and magnetic properties of spin-1/2 dimer compound Cu2(IPA)2(DMF)(H2O)
      with a large spin gap.
AB  - We present the synthesis and a detailed investigation of structural and magnetic
      properties of metal-organic compound Cu2(IPA)2(DMF)(H2O) by means of x-ray
      diffraction, magnetization, and heat capacity measurements. Single crystals of
      the title compound were synthesized by judicious selection of organic ligand and
      employing a selective hydrothermal reaction route. It crystallizes in an
      orthorhombic structure with space group Cmca. The structural analysis revealed
      that two Cu2+ ions are held together by the organic component (-O-C-O-) in a
      square paddle-wheel to form spin dimers which are aligned perpendicular to each
      other and are further coupled through organic ligands (isophthalic acid) forming
      two-dimensional layers. Temperature dependent magnetic susceptibility [Formula:
      see text] could be described well using spin-1/2 dimer model. The spin
      susceptibility [Formula: see text] shows an exponential decrease in the low
      temperature region, below the broad maximum, confirming the singlet ground state
      with a large spin gap of [Formula: see text] K. The heat capacity C p measured as
      a function of temperature also confirms the absence of magnetic long-range-order
      down to 2 K.

PMID- 28516899
TI  - All-dielectric resonant cavity-enabled metals with broadband optical
      transparency.
AB  - Metal films with broadband optical transparency are desirable in many
      optoelectronic devices, such as displays, smart windows, light-emitting diodes
      and infrared detectors. As bare metal is opaque to light, this issue of
      transparency attracts great scientific interest. In this work, we proposed and
      demonstrated a feasible and universal approach for achieving broadband optical
      transparent (BOT) metals by utilizing all-dielectric resonant cavities. Resonant
      dielectrics provide optical cavity modes and couple strongly with the surface
      plasmons of the metal film, and therefore produce a broadband near-unity optical
      transparent window. The relative enhancement factor (EF) of light transmission
      exceeds 3400% in comparison with that of pure metal film. Moreover, the
      transparent metal motif can be realized by other common metals including gold
      (Au), silver (Ag) and copper (Cu). These optical features together with the fully
      retained electric and mechanical properties of a natural metal suggest that it
      will have wide applications in optoelectronic devices.

PMID- 28516900
TI  - Facile preparation of protonated hexaniobate nanosheets and its enhanced
      photocatalytic activity.
AB  - Exfoliated hexaniobate nanosheets E-H2K2Nb6O17-x (E-HKNO) with broad light
      absorption (up to 850 nm) and high adsorption properties were prepared via ion
      exchange and transient annealing processes with micron-size K4Nb6O17 powders as
      the precursor. The as-prepared E-HKNO nanosheets show excellent visible light
      photodegradation performances when compared to degussa P25, which was evaluated
      in terms of degradation of Rhodamine B (Rh B). High adsorption and broad light
      absorption characteristics could be attributed to the exfoliation behavior and
      the reduction of surface Nb5+ to Nb4+, which was confirmed by x-ray photoelectron
      spectroscopy (XPS) and Raman spectra. From the Mott-Schottky analysis, the E-HKNO
      is an n-type semiconductor and has a higher flat band voltage (-0.46 V versus RHE
      at pH = 7), compared with K4Nb6O17. In addition, the electrochemical impedance
      spectroscopy (EIS) indicates that the E-HKNO nanosheets have an increased
      semiconductor-electrolyte charge transfer resistance, which is not conducive to
      the separation of photogenerated carriers (e--h+). Accordingly, a small amount of
      holes scavenger (EDTA) was added to improve the photodegradation performance of
      the E-HKNO, since the holes scavenger can inhibit the recombination of the
      photogenerated carriers. This work provides not only a facile method for the
      preparation of an efficient E-HKNO nanosheets photocatalyst, but also new
      insights for further enhancing the photodegradation performance by adding trace
      scavenger.

PMID- 28516901
TI  - EEG source space analysis of the supervised factor analytic approach for the
      classification of multi-directional arm movement.
AB  - OBJECTIVE: In electroencephalography (EEG)-based brain-computer interface (BCI)
      systems for motor control tasks the conventional practice is to decode motor
      intentions by using scalp EEG. However, scalp EEG only reveals certain limited
      information about the complex tasks of movement with a higher degree of freedom.
      Therefore, our objective is to investigate the effectiveness of source-space EEG
      in extracting relevant features that discriminate arm movement in multiple
      directions. APPROACH: We have proposed a novel feature extraction algorithm based
      on supervised factor analysis that models the data from source-space EEG. To this
      end, we computed the features from the source dipoles confined to Brodmann areas
      of interest (BA4a, BA4p and BA6). Further, we embedded class-wise labels of multi
      direction (multi-class) source-space EEG to an unsupervised factor analysis to
      make it into a supervised learning method. MAIN RESULTS: Our approach provided an
      average decoding accuracy of 71% for the classification of hand movement in four
      orthogonal directions, that is significantly higher (>10%) than the
      classification accuracy obtained using state-of-the-art spatial pattern features
      in sensor space. Also, the group analysis on the spectral characteristics of
      source-space EEG indicates that the slow cortical potentials from a set of
      cortical source dipoles reveal discriminative information regarding the movement
      parameter, direction. SIGNIFICANCE: This study presents evidence that low
      frequency components in the source space play an important role in movement
      kinematics, and thus it may lead to new strategies for BCI-based
      neurorehabilitation.

PMID- 28516902
TI  - Role of Transient Receptor Potential Channels in Heart Transplantation: A
      Potential Novel Therapeutic Target for Cardiac Allograft Vasculopathy.
AB  - Heart transplantation has evolved as the criterion standard therapy for end-stage
      heart failure, but its efficacy is limited by the development of cardiac
      allograft vasculopathy (CAV), a unique and rapidly progressive form of
      atherosclerosis in heart transplant recipients. Here, we briefly review the key
      processes in the development of CAV during heart transplantation and highlight
      the roles of transient receptor potential (TRP) channels in these processes
      during heart transplantation. Understanding the roles of TRP channels in
      contributing to the key procedures for the development of CAV during heart
      transplantation could provide basic scientific knowledge for the development of
      new preventive and therapeutic approaches to manage patients with CAV after heart
      transplantation.

PMID- 28516905
TI  - The effects of forest canopy shading and turbulence on boundary layer ozone.
AB  - The chemistry of the Earth's atmosphere close to the surface is known to be
      strongly influenced by vegetation. However, two critical aspects of the forest
      environment have been neglected in the description of the large-scale influence
      of forests on air pollution: the reduction of photolysis reaction rates and the
      modification of vertical transport due to the presence of foliage. Here we show
      that foliage shading and foliage-modified vertical diffusion have a profound
      influence on atmospheric chemistry, both at the Earth's surface and extending
      throughout the atmospheric boundary layer. The absence of these processes in
      three-dimensional models may account for 59-72% of the positive bias in North
      American surface ozone forecasts, and up to 97% of the bias in forested regions
      within the continent. These processes are shown to have similar or greater
      influence on surface ozone levels as climate change and current emissions policy
      scenario simulations.

PMID- 28516903
TI  - Molecular mechanism of Galphai activation by non-GPCR proteins with a Galpha
      Binding and Activating motif.
AB  - Heterotrimeric G proteins are quintessential signalling switches activated by
      nucleotide exchange on Galpha. Although activation is predominantly carried out
      by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange
      factors (GEFs) have emerged as critical signalling molecules and therapeutic
      targets. Here we characterize the molecular mechanism of G-protein activation by
      a family of non-receptor GEFs containing a Galpha-binding and -activating (GBA)
      motif. We combine NMR spectroscopy, computational modelling and biochemistry to
      map changes in Galpha caused by binding of GBA proteins with residue-level
      resolution. We find that the GBA motif binds to the SwitchII/alpha3 cleft of
      Galpha and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate
      binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal
      that G-protein-binding and activation mechanisms are fundamentally different
      between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide
      phosphate binding is sufficient for Galpha activation.

PMID- 28516906
TI  - Nanometric holograms based on a topological insulator material.
AB  - Holography has extremely extensive applications in conventional optical
      instruments spanning optical microscopy and imaging, three-dimensional displays
      and metrology. To integrate holography with modern low-dimensional electronic
      devices, holograms need to be thinned to a nanometric scale. However, to keep a
      pronounced phase shift modulation, the thickness of holograms has been generally
      limited to the optical wavelength scale, which hinders their integration with
      ultrathin electronic devices. Here, we break this limit and achieve 60 nm
      holograms using a topological insulator material. We discover that nanometric
      topological insulator thin films act as an intrinsic optical resonant cavity due
      to the unequal refractive indices in their metallic surfaces and bulk. The
      resonant cavity leads to enhancement of phase shifts and thus the holographic
      imaging. Our work paves a way towards integrating holography with flat electronic
      devices for optical imaging, data storage and information security.

PMID- 28516904
TI  - Lhx1/5 control dendritogenesis and spine morphogenesis of Purkinje cells via
      regulation of Espin.
AB  - In the cerebellar cortex, Purkinje cells (PCs) receive signals from different
      inputs through their extensively branched dendrites and serve as an integration
      centre. Defects in the dendritic development of PCs thus disrupt cerebellar
      circuitry and cause ataxia. Here we report that specific inactivation of both
      Lhx1 and Lhx5 in postnatal PCs results in ataxic mutant mice with abnormal
      dendritic development. The PCs in the mutants have reduced expression of Espin,
      an F-actin cytoskeleton regulator. We show that Espin expression is
      transcriptionally activated by Lhx1/5. Downregulation of Espin leads to F-actin
      mislocalization, thereby impairing dendritogenesis and dendritic spine maturation
      in the PCs. The mutant PCs therefore fail to form proper synapses and show
      aberrant electrophysiological properties. By overexpressing Espin, we can
      successfully rescue the defects in the mutant PCs. Our findings suggest that
      Lhx1/5, through regulating Espin expression, control dendritogenesis and spine
      morphogenesis in postnatal PCs.

PMID- 28516907
TI  - Vagal determinants of exercise capacity.
AB  - Indirect measures of cardiac vagal activity are strongly associated with exercise
      capacity, yet a causal relationship has not been established. Here we show that
      in rats, genetic silencing of the largest population of brainstem vagal
      preganglionic neurons residing in the brainstem's dorsal vagal motor nucleus
      dramatically impairs exercise capacity, while optogenetic recruitment of the same
      neuronal population enhances cardiac contractility and prolongs exercise
      endurance. These data provide direct experimental evidence that parasympathetic
      vagal drive generated by a defined CNS circuit determines the ability to
      exercise. Decreased activity and/or gradual loss of the identified neuronal cell
      group provides a neurophysiological basis for the progressive decline of exercise
      capacity with aging and in diverse disease states.

PMID- 28516908
TI  - An optimized strategy to measure protein stability highlights differences between
      cold and hot unfolded states.
AB  - Macromolecular crowding ought to stabilize folded forms of proteins, through an
      excluded volume effect. This explanation has been questioned and observed effects
      attributed to weak interactions with other cell components. Here we show
      conclusively that protein stability is affected by volume exclusion and that the
      effect is more pronounced when the crowder's size is closer to that of the
      protein under study. Accurate evaluation of the volume exclusion effect is made
      possible by the choice of yeast frataxin, a protein that undergoes cold
      denaturation above zero degrees, because the unfolded form at low temperature is
      more expanded than the corresponding one at high temperature. To achieve optimum
      sensitivity to changes in stability we introduce an empirical parameter derived
      from the stability curve. The large effect of PEG 20 on cold denaturation can be
      explained by a change in water activity, according to Privalov's interpretation
      of cold denaturation.

PMID- 28516909
TI  - Heat guiding and focusing using ballistic phonon transport in phononic
      nanostructures.
AB  - Unlike classical heat diffusion at macroscale, nanoscale heat conduction can
      occur without energy dissipation because phonons can ballistically travel in
      straight lines for hundreds of nanometres. Nevertheless, despite recent
      experimental evidence of such ballistic phonon transport, control over its
      directionality, and thus its practical use, remains a challenge, as the
      directions of individual phonons are chaotic. Here, we show a method to control
      the directionality of ballistic phonon transport using silicon membranes with
      arrays of holes. First, we demonstrate that the arrays of holes form fluxes of
      phonons oriented in the same direction. Next, we use these nanostructures as
      directional sources of ballistic phonons and couple the emitted phonons into
      nanowires. Finally, we introduce thermal lens nanostructures, in which the
      emitted phonons converge at the focal point, thus focusing heat into a spot of a
      few hundred nanometres. These results motivate the concept of ray-like heat
      manipulations at the nanoscale.

PMID- 28516912
TI  - A complete tool set for molecular QTL discovery and analysis.
AB  - Population scale studies combining genetic information with molecular phenotypes
      (for example, gene expression) have become a standard to dissect the effects of
      genetic variants onto organismal phenotypes. These kinds of data sets require
      powerful, fast and versatile methods able to discover molecular Quantitative
      Trait Loci (molQTL). Here we propose such a solution, QTLtools, a modular
      framework that contains multiple new and well-established methods to prepare the
      data, to discover proximal and distal molQTLs and, finally, to integrate them
      with GWAS variants and functional annotations of the genome. We demonstrate its
      utility by performing a complete expression QTL study in a few easy-to-perform
      steps. QTLtools is open source and available at
      https://qtltools.github.io/qtltools/.

PMID- 28516910
TI  - Genetic architecture of epigenetic and neuronal ageing rates in human brain
      regions.
AB  - Identifying genes regulating the pace of epigenetic ageing represents a new
      frontier in genome-wide association studies (GWASs). Here using 1,796 brain
      samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based
      biomarkers of brain age: the epigenetic ageing rate and estimated proportion of
      neurons. Locus 17q11.2 is significantly associated (P=4.5 * 10-9) with the ageing
      rate across five brain regions and harbours a cis-expression quantitative trait
      locus for EFCAB5 (P=3.4 * 10-20). Locus 1p36.12 is significantly associated
      (P=2.2 * 10-8) with epigenetic ageing of the prefrontal cortex, independent of
      the proportion of neurons. Our GWAS of the proportion of neurons identified two
      genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that
      overlaps significantly with sets found by GWAS of age-related macular
      degeneration (P=1.4 * 10-12), ulcerative colitis (P<1.0 * 10-20), type 2 diabetes
      (P=2.8 * 10-13), hip/waist circumference in men (P=1.1 * 10-9), schizophrenia
      (P=1.6 * 10-9), cognitive decline (P=5.3 * 10-4) and Parkinson's disease (P=8.6 *
      10-3).

PMID- 28516911
TI  - Electrostatic melting in a single-molecule field-effect transistor with
      applications in genomic identification.
AB  - The study of biomolecular interactions at the single-molecule level holds great
      potential for both basic science and biotechnology applications. Single-molecule
      studies often rely on fluorescence-based reporting, with signal levels limited by
      photon emission from single optical reporters. The point-functionalized carbon
      nanotube transistor, known as the single-molecule field-effect transistor, is a
      bioelectronics alternative based on intrinsic molecular charge that offers
      significantly higher signal levels for detection. Such devices are effective for
      characterizing DNA hybridization kinetics and thermodynamics and enabling
      emerging applications in genomic identification. In this work, we show that
      hybridization kinetics can be directly controlled by electrostatic bias applied
      between the device and the surrounding electrolyte. We perform the first single
      molecule experiments demonstrating the use of electrostatics to control molecular
      binding. Using bias as a proxy for temperature, we demonstrate the feasibility of
      detecting various concentrations of 20-nt target sequences from the Ebolavirus
      nucleoprotein gene in a constant-temperature environment.

PMID- 28516913
TI  - Self-folding origami at any energy scale.
AB  - Programmable stiff sheets with a single low-energy folding motion have been
      sought in fields ranging from the ancient art of origami to modern meta-materials
      research. Despite such attention, only two extreme classes of crease patterns are
      usually studied; special Miura-Ori-based zero-energy patterns, in which crease
      folding requires no sheet bending, and random patterns with high-energy folding,
      in which the sheet bends as much as creases fold. We present a physical approach
      that allows systematic exploration of the entire space of crease patterns as a
      function of the folding energy. Consequently, we uncover statistical results in
      origami, finding the entropy of crease patterns of given folding energy. Notably,
      we identify three classes of Mountain-Valley choices that have widely varying
      'typical' folding energies. Our work opens up a wealth of experimentally relevant
      self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or
      any special symmetry in space.

PMID- 28516914
TI  - Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells
      by facilitating LDHA phosphorylation.
AB  - Targeting the specific metabolic phenotypes of colorectal cancer stem cells
      (CRCSCs) is an innovative therapeutic strategy for colorectal cancer (CRC)
      patients with poor prognosis and relapse. However, the context-dependent
      metabolic traits of CRCSCs remain poorly elucidated. Here we report that
      adenylate kinase hCINAP is overexpressed in CRC tissues. Depletion of hCINAP
      inhibits invasion, self-renewal, tumorigenesis and chemoresistance of CRCSCs with
      a loss of mesenchymal signature. Mechanistically, hCINAP binds to the C-terminal
      domain of LDHA, the key regulator of glycolysis, and depends on its adenylate
      kinase activity to promote LDHA phosphorylation at tyrosine 10, resulting in the
      hyperactive Warburg effect and the lower cellular ROS level and conferring
      metabolic advantage to CRCSC invasion. Moreover, hCINAP expression is positively
      correlated with the level of Y10-phosphorylated LDHA in CRC patients. This study
      identifies hCINAP as a potent modulator of metabolic reprogramming in CRCSCs and
      a promising drug target for CRC invasion and metastasis.

PMID- 28516915
TI  - Equilibrium oxygen storage capacity of ultrathin CeO2-delta depends non
      monotonically on large biaxial strain.
AB  - Elastic strain is being increasingly employed to enhance the catalytic properties
      of mixed ion-electron conducting oxides. However, its effect on oxygen storage
      capacity is not well established. Here, we fabricate ultrathin, coherently
      strained films of CeO2-delta between 5.6% biaxial compression and 2.1% tension.
      In situ ambient pressure X-ray photoelectron spectroscopy reveals up to a
      fourfold enhancement in equilibrium oxygen storage capacity under both
      compression and tension. This non-monotonic variation with strain departs from
      the conventional wisdom based on a chemical expansion dominated behaviour.
      Through depth profiling, film thickness variations and a coupled photoemission
      thermodynamic analysis of space-charge effects, we show that the enhanced
      reducibility is not dominated by interfacial effects. On the basis of ab initio
      calculations of oxygen vacancy formation incorporating defect interactions and
      vibrational contributions, we suggest that the non-monotonicity arises from the
      tetragonal distortion under large biaxial strain. These results may guide the
      rational engineering of multilayer and core-shell oxide nanomaterials.

PMID- 28516916
TI  - Unified model for singlet fission within a non-conjugated covalent pentacene
      dimer.
AB  - When molecular dimers, crystalline films or molecular aggregates absorb a photon
      to produce a singlet exciton, spin-allowed singlet fission may produce two
      triplet excitons that can be used to generate two electron-hole pairs, leading to
      a predicted ~50% enhancement in maximum solar cell performance. The singlet
      fission mechanism is still not well understood. Here we report on the use of time
      resolved optical and electron paramagnetic resonance spectroscopy to probe
      singlet fission in a pentacene dimer linked by a non-conjugated spacer. We
      observe the key intermediates in the singlet fission process, including the
      formation and decay of a quintet state that precedes formation of the pentacene
      triplet excitons. Using these combined data, we develop a single kinetic model
      that describes the data over seven temporal orders of magnitude both at room and
      cryogenic temperatures.

PMID- 28516918
TI  - In Retrospect: Half a century of robust climate models.

PMID- 28516919
TI  - Atomic physics: Quantum theory verified by experiment.

PMID- 28516921
TI  - Behavioural economics: Occasional errors can benefit coordination.

PMID- 28516917
TI  - Maternal age-dependent APC/C-mediated decrease in securin causes premature sister
      chromatid separation in meiosis II.
AB  - Sister chromatid attachment during meiosis II (MII) is maintained by securin
      mediated inhibition of separase. In maternal ageing, oocytes show increased inter
      sister kinetochore distance and premature sister chromatid separation (PSCS),
      suggesting aberrant separase activity. Here, we find that MII oocytes from aged
      mice have less securin than oocytes from young mice and that this reduction is
      mediated by increased destruction by the anaphase promoting complex/cyclosome
      (APC/C) during meiosis I (MI) exit. Inhibition of the spindle assembly checkpoint
      (SAC) kinase, Mps1, during MI exit in young oocytes replicates this phenotype.
      Further, over-expression of securin or Mps1 protects against the age-related
      increase in inter-sister kinetochore distance and PSCS. These findings show that
      maternal ageing compromises the oocyte SAC-APC/C axis leading to a decrease in
      securin that ultimately causes sister chromatid cohesion loss. Manipulating this
      axis and/or increasing securin may provide novel therapeutic approaches to
      alleviating the risk of oocyte aneuploidy in maternal ageing.

PMID- 28516920
TI  - China: Rail network must protect giant pandas.

PMID- 28516922
TI  - Multidisciplinarity: Widen discipline span of Nature papers.

PMID- 28516925
TI  - Global health: Boost multinational clinical research.

PMID- 28516929
TI  - Hans Dehmelt (1922-2017).

PMID- 28516927
TI  - Locally noisy autonomous agents improve global human coordination in network
      experiments.
AB  - Coordination in groups faces a sub-optimization problem and theory suggests that
      some randomness may help to achieve global optima. Here we performed experiments
      involving a networked colour coordination game in which groups of humans
      interacted with autonomous software agents (known as bots). Subjects (n = 4,000)
      were embedded in networks (n = 230) of 20 nodes, to which we sometimes added 3
      bots. The bots were programmed with varying levels of behavioural randomness and
      different geodesic locations. We show that bots acting with small levels of
      random noise and placed in central locations meaningfully improve the collective
      performance of human groups, accelerating the median solution time by 55.6%. This
      is especially the case when the coordination problem is hard. Behavioural
      randomness worked not only by making the task of humans to whom the bots were
      connected easier, but also by affecting the gameplay of the humans among
      themselves and hence creating further cascades of benefit in global coordination
      in these heterogeneous systems.

PMID- 28516930
TI  - Seismology: Japan must admit it can't predict quakes.

PMID- 28516932
TI  - Correction.

PMID- 28516933
TI  - Experimental characterization of a quantum many-body system via higher-order
      correlations.
AB  - Quantum systems can be characterized by their correlations. Higher-order (larger
      than second order) correlations, and the ways in which they can be decomposed
      into correlations of lower order, provide important information about the system,
      its structure, its interactions and its complexity. The measurement of such
      correlation functions is therefore an essential tool for reading, verifying and
      characterizing quantum simulations. Although higher-order correlation functions
      are frequently used in theoretical calculations, so far mainly correlations up to
      second order have been studied experimentally. Here we study a pair of tunnel
      coupled one-dimensional atomic superfluids and characterize the corresponding
      quantum many-body problem by measuring correlation functions. We extract phase
      correlation functions up to tenth order from interference patterns and analyse
      whether, and under what conditions, these functions factorize into correlations
      of lower order. This analysis characterizes the essential features of our system,
      the relevant quasiparticles, their interactions and topologically distinct vacua.
      From our data we conclude that in thermal equilibrium our system can be seen as a
      quantum simulator of the sine-Gordon model, relevant for diverse disciplines
      ranging from particle physics to condensed matter. The measurement and evaluation
      of higher-order correlation functions can easily be generalized to other systems
      and to study correlations of any other observable such as density, spin and
      magnetization. It therefore represents a general method for analysing quantum
      many-body systems from experimental data.

PMID- 28516934
TI  - Rescue old data before it's too late.

PMID- 28516935
TI  - How Trump's science cuts could hurt states that voted for him.

PMID- 28516937
TI  - Ebola outbreak in the Congo, tuberculosis drug resistance in Russia and GM
      mustard seeds in India.

PMID- 28516936
TI  - Biology needs more staff scientists.

PMID- 28516938
TI  - Keep doors open for constructive dialogue between religion and science.

PMID- 28516939
TI  - China cracks down on fake data in drug trials.

PMID- 28516940
TI  - The United States must act quickly to control the use of e-cigarettes.

PMID- 28516941
TI  - The wooden skyscrapers that could help to cool the planet.

PMID- 28516942
TI  - Ancient-genome study finds Bronze Age 'Beaker culture' invaded Britain.

PMID- 28516943
TI  - Why US nuclear sites are a ticking time bomb.

PMID- 28516944
TI  - Century-old tumours offer rare cancer clues.

PMID- 28516945
TI  - Geneticists enlist engineered virus and CRISPR to battle citrus disease.

PMID- 28516947
TI  - Artificial local magnetic field inhomogeneity enhances T2 relaxivity.
AB  - Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet
      intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI).
      However, the underlying mechanism is still not fully understood and the attempts
      to generalize the classic outersphere theory from single particles to clusters
      have been found to be inadequate. Here we show that clustering of MNPs enhances
      local field inhomogeneity due to reduced field symmetry, which can be further
      elevated by artificially involving iron oxide NPs with heterogeneous geometries
      in terms of size and shape. The r2 values of iron oxide clusters and Landau
      Lifshitz-Gilbert simulations confirmed our hypothesis, indicating that solving
      magnetic field inhomogeneity may become a powerful way to build correlation
      between magnetization and T2 relaxivity of MNPs, especially magnetic clusters.
      This study provides a simple yet distinct mechanism to interpret T2 relaxivity of
      MNPs, which is crucial to the design of high-performance MRI contrast agents.

PMID- 28516946
TI  - Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that
      rescues delayed maternal wound healing.
AB  - Foetal microchimeric cells (FMCs) traffic into maternal circulation during
      pregnancy and persist for decades after delivery. Upon maternal injury, FMCs
      migrate to affected sites where they participate in tissue healing. However, the
      specific signals regulating the trafficking of FMCs to injury sites had to be
      identified. Here we report that, in mice, a subset of FMCs implicated in tissue
      repair displays CD11b+ CD34+ CD31+ phenotype and highly express C-C chemokine
      receptor 2 (Ccr2). The Ccr2 ligand chemokine ligand 2 (Ccl2) enhances the
      recruitment of FMCs to maternal wounds where these cells transdifferentiate into
      endothelial cells and stimulate angiogenesis through Cxcl1 secretion. Ccl2
      administration improves delayed maternal wound healing in pregnant and postpartum
      mice but never in virgin ones. This role of Ccl2/Ccr2 signalling opens new
      strategies for tissue repair through natural stem cell therapy, a concept that
      can be later applied to other types of maternal diseases.

PMID- 28516949
TI  - Paroxysmal nocturnal haemoglobinuria.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell
      (HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle
      dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic
      mutations in PIGA (which encodes phosphatidylinositol N
      acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene
      product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol
      (GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored
      proteins, such as complement decay-accelerating factor (also known as CD55) and
      CD59 glycoprotein (CD59), which are both complement inhibitors. Clinical
      manifestations of PNH occur when a HSC clone carrying somatic PIGA mutations
      acquires a growth advantage and differentiates, generating mature blood cells
      that are deficient of GPI-anchored proteins. The loss of CD55 and CD59 renders
      PNH erythrocytes susceptible to intravascular haemolysis, which can lead to
      thrombosis and to much of the morbidity and mortality of PNH. The accumulation of
      anaphylatoxins (such as C5a) from complement activation might also have a role.
      The natural history of PNH is highly variable, ranging from quiescent to life
      threatening. Therapeutic strategies include terminal complement blockade and bone
      marrow transplantation. Eculizumab, a monoclonal antibody complement inhibitor,
      is highly effective and the only licensed therapy for PNH.

PMID- 28516950
TI  - High conductance values in pi-folded molecular junctions.
AB  - Folding processes play a crucial role in the development of function in
      biomacromolecules. Recreating this feature on synthetic systems would not only
      allow understanding and reproducing biological functions but also developing new
      functions. This has inspired the development of conformationally ordered
      synthetic oligomers known as foldamers. Herein, a new family of foldamers,
      consisting of an increasing number of anthracene units that adopt a folded
      sigmoidal conformation by a combination of intramolecular hydrogen bonds and
      aromatic interactions, is reported. Such folding process opens up an efficient
      through-space charge transport channel across the interacting anthracene
      moieties. In fact, single-molecule conductance measurements carried out on this
      series of foldamers, using the scanning tunnelling microscopy-based break
      junction technique, reveal exceptionally high conductance values in the order of
      10-1 G0 and a low length decay constant of 0.02 A-1 that exceed the values
      observed in molecular junctions that make use of through-space charge transport
      pathways.

PMID- 28516951
TI  - Improving 10-deacetylbaccatin III-10-beta-O-acetyltransferase catalytic fitness
      for Taxol production.
AB  - The natural concentration of the anticancer drug Taxol is about 0.02% in yew
      trees, whereas that of its analogue 7-beta-xylosyl-10-deacetyltaxol is up to
      0.5%. While this compound is not an intermediate in Taxol biosynthetic route, it
      can be converted into Taxol by de-glycosylation and acetylation. Here, we improve
      the catalytic efficiency of 10-deacetylbaccatin III-10-O-acetyltransferase (DBAT)
      of Taxus towards 10-deacetyltaxol, a de-glycosylated derivative of 7-beta-xylosyl
      10-deacetyltaxol to generate Taxol using mutagenesis. We generate a three
      dimensional structure of DBAT and identify its active site using alanine scanning
      and design a double DBAT mutant (DBATG38R/F301V) with a catalytic efficiency
      approximately six times higher than that of the wild-type. We combine this mutant
      with a beta-xylosidase to obtain an in vitro one-pot conversion of 7-beta-xylosyl
      10-deacetyltaxol to Taxol yielding 0.64 mg ml-1 Taxol in 50 ml at 15 h. This
      approach represents a promising environmentally friendly alternative for Taxol
      production from an abundant analogue.

PMID- 28516952
TI  - Solid frustrated-Lewis-pair catalysts constructed by regulations on surface
      defects of porous nanorods of CeO2.
AB  - Identification on catalytic sites of heterogeneous catalysts at atomic level is
      important to understand catalytic mechanism. Surface engineering on defects of
      metal oxides can construct new active sites and regulate catalytic activity and
      selectivity. Here we outline the strategy by controlling surface defects of
      nanoceria to create the solid frustrated Lewis pair (FLP) metal oxide for
      efficient hydrogenation of alkenes and alkynes. Porous nanorods of ceria (PN
      CeO2) with a high concentration of surface defects construct new Lewis acidic
      sites by two adjacent surface Ce3+. The neighbouring surface lattice oxygen as
      Lewis base and constructed Lewis acid create solid FLP site due to the rigid
      lattice of ceria, which can easily dissociate H-H bond with low activation energy
      of 0.17 eV.

PMID- 28516953
TI  - Signal recognition particle prevents N-terminal processing of bacterial membrane
      proteins.
AB  - Bacterial proteins are synthesized with an N-formylated amino-terminal
      methionine, and N-formylated peptides elicit innate-immunity responses against
      bacterial infections. However, the source of these formylated peptides is not
      clear, as most bacterial proteins are co-translationally deformylated by peptide
      deformylase. Here we develop a deformylation assay with translating ribosomes as
      substrates, to show that the binding of the signal recognition particle (SRP) to
      signal sequences in nascent proteins on the ribosome prevents deformylation,
      whereas deformylation of nascent proteins without signal sequence is not
      affected. Deformylation and its inhibition by SRP are not influenced by trigger
      factor, a chaperone that interacts with nascent chains on the ribosome. We
      propose that bacterial inner-membrane proteins, in particular those with N-out
      topology, can retain their N-terminal formyl group during cotranslational
      membrane insertion and supply formylated peptides during bacterial infections.

PMID- 28516955
TI  - Spectral correlations in a random distributed feedback fibre laser.
AB  - Random distributed feedback fibre lasers belong to the class of random lasers,
      where the feedback is provided by amplified Rayleigh scattering on sub-micron
      refractive index inhomogenities randomly distributed over the fibre length.
      Despite the elastic nature of Rayleigh scattering, the feedback mechanism has
      been insofar deemed incoherent, which corresponds to the commonly observed smooth
      generation spectra. Here, using a real-time spectral measurement technique based
      on a scanning Fabry-Perot interferometer, we observe long-living narrowband
      components in the random fibre laser's spectrum. Statistical analysis of the ~104
      single-scan spectra reveals a preferential interspacing for the components and
      their anticorrelation in intensities. Furthermore, using mutual information
      analysis, we confirm the existence of nonlinear correlations between different
      parts of the random fibre laser spectra. The existence of such narrowband
      spectral components, together with their observed correlations, establishes a
      long-missing parallel between the fields of random fibre lasers and conventional
      random lasers.

PMID- 28516954
TI  - Histone deacetylase 10 structure and molecular function as a polyamine
      deacetylase.
AB  - Cationic polyamines such as spermidine and spermine are critical in all forms of
      life, as they regulate the function of biological macromolecules. Intracellular
      polyamine metabolism is regulated by reversible acetylation and dysregulated
      polyamine metabolism is associated with neoplastic diseases such as colon cancer,
      prostate cancer and neuroblastoma. Here we report that histone deacetylase 10
      (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo
      sapiens (human) and Danio rerio (zebrafish). The 2.85 A-resolution crystal
      structure of zebrafish HDAC10 complexed with a transition-state analogue
      inhibitor reveals that a glutamate gatekeeper and a sterically constricted active
      site confer specificity for N8-acetylspermidine hydrolysis and disfavour
      acetyllysine hydrolysis. Both HDAC10 and spermidine are known to promote cellular
      survival through autophagy. Accordingly, this work sets a foundation for studying
      the chemical biology of autophagy through the structure-based design of
      inhibitors that may also serve as new leads for cancer chemotherapy.

PMID- 28516958
TI  - The origin and degassing history of the Earth's atmosphere revealed by Archean
      xenon.
AB  - Xenon (Xe) is an exceptional tracer for investigating the origin and fate of
      volatile elements on Earth. The initial isotopic composition of atmospheric Xe
      remains unknown, as do the mechanisms involved in its depletion and isotopic
      fractionation compared with other reservoirs in the solar system. Here we present
      high precision analyses of noble gases trapped in fluid inclusions of Archean
      quartz (Barberton, South Africa) that reveal the isotopic composition of the
      paleo-atmosphere at ~3.3 Ga. The Archean atmospheric Xe is mass-dependently
      fractionated by 12.9+/-2.4 0/00 u-1 (+/- 2sigma, s.d.) relative to the modern
      atmosphere. The lower than today 129Xe excess requires a degassing rate of
      radiogenic Xe from the mantle higher than at present. The primordial Xe component
      delivered to the Earth's atmosphere is distinct from Solar or Chondritic Xe but
      similar to a theoretical component called U-Xe. Comets may have brought this
      component to the Earth's atmosphere during the last stages of terrestrial
      accretion.

PMID- 28516956
TI  - Selective BET bromodomain inhibition as an antifungal therapeutic strategy.
AB  - Invasive fungal infections cause significant morbidity and mortality among
      immunocompromised individuals, posing an urgent need for new antifungal
      therapeutic strategies. Here we investigate a chromatin-interacting module, the
      bromodomain (BD) from the BET family of proteins, as a potential antifungal
      target in Candida albicans, a major human fungal pathogen. We show that the BET
      protein Bdf1 is essential in C. albicans and that mutations inactivating its two
      BDs result in a loss of viability in vitro and decreased virulence in mice. We
      report small-molecule compounds that inhibit C. albicans Bdf1 with high
      selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding
      modes for these inhibitors that are sterically incompatible with the human BET
      binding pockets. Furthermore, we report a dibenzothiazepinone compound that
      phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans
      viability. These findings establish BET inhibition as a promising antifungal
      therapeutic strategy and identify Bdf1 as an antifungal drug target that can be
      selectively inhibited without antagonizing human BET function.

PMID- 28516957
TI  - ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour
      suppressor in leukemia.
AB  - Additional sex combs-like (ASXL) proteins are mammalian homologues of additional
      sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila.
      While there has been great interest in ASXL1 due to its frequent mutation in
      leukemia, little is known about its paralog ASXL2, which is frequently mutated in
      acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here
      we report that ASXL2 is required for normal haematopoiesis with distinct, non
      overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor.
      While Asxl2 was required for normal haematopoietic stem cell self-renewal, Asxl2
      loss promoted AML1-ETO leukemogenesis. Moreover, ASXL2 target genes strongly
      overlapped with those of RUNX1 and AML1-ETO and ASXL2 loss was associated with
      increased chromatin accessibility at putative enhancers of key leukemogenic loci.
      These data reveal that Asxl2 is a critical regulator of haematopoiesis and
      mediates transcriptional effects that promote leukemogenesis driven by AML1-ETO.

PMID- 28516960
TI  - Clinicopathologic idiosyncrasies of nasopharyngeal cancer in a moderate-risk
      Mediterranean region.
AB  - Cancer of the nasopharynx displays an unparalleled skewness of its epidemiologic,
      pathogenic and clinico-prognostic characteristics depending on the geographic
      location. Between the endemic and sporadic forms, which occur in Southeastern
      Asia and Northern America, respectively, intermediate incidence is noted around
      the Mediterranean. This study describes the patterns of the disease affecting the
      population of Western Greece. The records of 70 patients with nasopharyngeal
      cancer diagnosed in a single institution between 1994-2014 were retrospectively
      reviewed. Primary treatment involved irradiation with or without concurrent
      chemotherapy. Demographic data, patient risk factors, tumour parameters, clinical
      presentation and treatment outcomes were assessed for potential
      intercorrelations. Overall (OS) and disease-specific (DSS) 5-year survival rates
      were determined. Possible predictors of survival were tested on univariate and
      multivariate analysis. WHO-type 3 histopathology was diagnosed predominantly
      (74.3%) and associated significantly with nasal symptomatology upon presentation
      (p = 0.050), metastatic lymphadenopathy (p = 0.028), advanced clinical stage (p =
      0.009) and complete response to initial treatment (p = 0.018). Univariate
      analysis revealed a negative prognostic significance for older age (OS, p = 0.029
      DSS, p = 0.041), poor response to treatment (OS & DSS p < 0.001) and cancer
      recurrence (OS, p = 0.003 DSS, p = 0.001). On multivariate analysis, disease
      relapse maintained its adverse effect (HR 7.442, 95% CI 2.199-25.187, p = 0.001).
      In conclusion, among nasopharyngeal carcinomas arising in western Greece,
      lymphoepitheliomas manifest a distinct clinical behaviour, so that their latest
      grouping along with WHO-type 2 tumours into the "non-keratinising" category may
      not apply. Regardless of pathology, cancer recurrence after initial remission is
      a severe event.

PMID- 28516959
TI  - Adaptive psychological structure in childhood hearing impairment: audiological
      correlations.
AB  - The present research deals with the clinical and social problems present during
      linguistic and cognitive development of deaf children. Currently, the development
      of Theory of Mind represents an important research field in deafness studies.
      These international studies highlighted a significant alteration in the
      development of Theory of Mind in deaf children compared to normal hearing
      children, especially in cases of congenital or preverbal hearing loss. In
      particular, the research focuses on the skills of deaf children in recognising
      emotions and desires, through both perceptive and cognitive methods, by
      evaluation of psycho-cognitive skills of children with severe hearing loss using
      a set of questions to be administered to hearing loss patients. The experiment
      was performed on a group composed of 10 children (5 males and 5 females) aged 4
      to 9 years and 54 to 108 months, affected by bilateral congenital hearing loss
      (severe to total), or hearing loss that developed in preverbal children the year
      before entering elementary school, or during the fourth year of elementary
      school. The selection criteria were based on: audiologic evaluation, neuro
      psychological tests administered to assess general, cognitive as well as praxis
      and perceptive abilities, and clinical observations performed to assess
      psychopathology using tests that assess development of both visual perceptive
      (Coloured Progressive Matrices) and graphic representational abilities (Test of
      Human Figure Drawings and the Family Drawing Test). The instrument "cognitive"
      was the "Deaf Children Series", arranged by us, that consists of a mental status
      examination (MSE) that evaluates: level of cognitive (knowledge-related) ability,
      emotional mood, and speech and thought patterns at the time of evaluation. Deaf
      children show a reduced responsiveness to the expressions of sadness on the
      perceptive side. Through the test, we observed a psychodynamic defense mechanism
      considering perceptive understanding performance. On the contrary, in normal
      hearing children, the emotion 'fear' is the most difficult to identify. Deaf
      children seem to be more susceptible to recognition of visual emotions.
      Furthermore, deaf children present significant problem-solving skills and
      emotional recognition skills, possibly as a result of their hearing impairment.

PMID- 28516962
TI  - Design of a customised bridging mandibular prosthesis for complex reconstruction:
      a pilot study.
AB  - The gold standard for mandibular reconstruction is universally recognised and
      consists of the replacement of the bony part of the mandible with a bony
      microvascular free flap supported by a reconstructive plate. Although this
      procedure is feasible and reproducible in most patients, at times poor
      oncological prognosis or poor performance status force surgeons to consider other
      reconstructive solutions. In these cases, the main alternative in reconstructing
      a mandibular defect is represented by bridging plates combined with soft tissue
      flaps. However, repairing a mandibular defect with a reconstructive plate only
      can lead to a series of diverse complications. The most frequent complications
      reported are rupture and oral exposure of the plate. In this paper, we describe a
      new method for mandibular reconstruction using a customised bridging mandibular
      prosthesis (CBMP) without bone free flap.

PMID- 28516963
TI  - The endoscopic evaluation of the oral phase of swallowing (Oral-FEES, O-FEES): a
      pilot study of the clinical use of a new procedure.
AB  - Oral FEES (O-FEES) is an endoscopic procedure conceived to directly visualise the
      oral phase of swallowing. In the perspective of clinical use, the feasibility,
      safety and acceptability of O-FEES has been evaluated. Subsequently, the
      procedure was compared with the radiological gold standard. The acceptability of
      O-FEES was compared to that of FEES using a 10 point questionnaire submitted to a
      sample of 52 outpatients complaining of swallowing disorders. Repeated measure
      analysis of variance (rm-ANOVA) models were used to test the mean difference of
      acceptability in the same subjects after FEES and O-FEES. Subsequently, another
      sample of 8 male outpatients underwent a simultaneous O-FEES and
      videofluoroscopic study (VFSS). The inter-rater reliability using 10 radiological
      landmarks, compared to O-FEES, was blindly determined between two raters. Inter
      rater agreement between the two judges for O-FEES and VFSS scores was assessed
      with the single score intra-class correlation coefficient (ICC). Differences
      between FEES and O-FEES answers for each question and among all the items
      considered overall were statistically significant (rm-ANOVA; F-statistic p <
      0.001). The inter-rater agreement concerning endoscopic and radiological
      evaluations between the two raters showed strong values of intra-class
      correlation coefficient (ICC) (95% confidence interval): 0.875 (0.373-0.979) and
      0.921 (0.542-0.986), respectively. The Bland-Altman test showed a bias of -0.24
      (95% limits of agreement; -1.77 to +1.19), which suggests that both methods
      produced almost identical results. In clinical practice and compared with FEES, O
      FEES is a well tolerated and safe procedure. Compared with the radiological gold
      standard, O-FEES offers reliable information about oral preparation and oral
      propulsion of the bolus.

PMID- 28516964
TI  - Barbed reposition pharyngoplasty in multilevel robotic surgery for obstructive
      sleep apnoea.
AB  - The surgical treatment of obstructive sleep apnoea in patients who are non
      compliant with continuous positive airway pressure therapy still represents a
      valid alternative. In recent years, the multilevel approach is becoming more
      diffuse in routine surgical practice, especially since the introduction of
      transoral robotic surgery. Barbed reposition pharyngoplasty in multilevel robotic
      surgery for OSA may represent a valid option to surgically approach the soft
      palate. Herein, we describe the technique and preliminary results of our
      experience.

PMID- 28516961
TI  - Supracricoid partial laryngectomy with crico-hyoido-epiglottopexy for glottic
      carcinoma with anterior commissure involvement.
AB  - Glottic cancers discovered at an early stage (T1-T2) can be treated with either
      radiotherapy or surgery. The aim of our study is to analyse survival and
      functional results of supra-cricoid partial laryngectomy (SCPL) with crico-hyoido
      epiglottopexy (CHEP) as surgical treatment for glottic carcinoma with anterior
      commissure involvement. We performed a retrospective study (1996-2013) which
      included patients who underwent SCPL-CHEP for glottic squamous cell carcinoma
      with involvement of the anterior commissure. Before surgery, all patients
      underwent staging including head, neck and chest CT-scan with contrast injection
      as well as suspension laryngoscopy under general anaesthesia. A total of 53
      patients were included. The median follow-up period was 124 months. Tumour
      resection was complete in 96.2% of cases. The overall, specific and recurrence
      free survival rates at 5 years were, respectively, 93.7%, 95.6% and 87.7%. The
      average period of hospitalisation was 18 days. The average time elapsed before
      decannulation and before restoration of oral feeding were 15 and 18 days,
      respectively. SCPL-CHEP is an important option for laryngeal surgical
      preservation. It allows adequate disease control as well as good functional
      results as long as the indications are well respected and the surgical techniques
      are mastered.

PMID- 28516965
TI  - Benefits of active middle ear implants over hearing aids in patients with sloping
      high tone hearing loss: comparison with hearing aids.
AB  - In this retrospective chart review we compared the subjective and objective
      benefits of active middle ear implants (AMEIs) with conventional hearing aids
      (HAs) in patients with sloping high tone hearing loss. Thirty-four patients with
      sensorineural hearing loss were treated with AMEIs. Of these, six had sloping
      high tone hearing loss and had worn an HA for more than 6 months. Objective
      assessments, a pure-tone audiogram, as well as a word recognition test, and the
      Korean version of the Hearing in Noise Test (K-HINT), and a subjective
      assessment, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire,
      were performed. Tests were conducted under three circumstances: 1) the unaided
      state before surgery; 2) the HA-aided state before surgery; and 3) the AMEI-aided
      state 3 months after surgery. The average high-frequency hearing gain (>= 2 kHz)
      was significantly better with AMEIs than with HAs. Although the result had no
      statistical significance, AMEIs showed a superior word recognition score (WRS)
      compared to HAs. However, the most comfortable hearing level at which the WRS was
      tested was significantly decreased with an AMEI compared to an HA. In the K-HINT,
      patients with an AMEI showed greater recognition than those fitted with an HA
      under both quiet and noisy conditions. The APAHB scores revealed that patients
      were more satisfied with an AMEI rather than an HA on all subscales. The use of
      vibroplasty in patients with sloping high tone loss resulted in positive hearing
      outcomes when compared to conventional HAs. Based on the data from this study,
      AMEIs provided better objective and subjective results and could, therefore, be a
      better alternative for the treatment of sloping hearing loss.

PMID- 28516966
TI  - Expanded transcanal transpromontorial approach to the internal auditory canal and
      cerebellopontine angle: a cadaveric study.
AB  - The aim of this paper is to describe and evaluate the feasibility of an expanded
      endoscopic transcanal transpromotorial approach (ExpTTA) to the internal auditory
      canal and the cerebellopontine angle. To this end, we performed a cadaveric
      dissection study in September 2015. In total, 2 heads (4 sides) were dissected
      focusing on anatomical landmarks and surgical feasibility. Data from dissections
      were reviewed and analysed for further consideration. In all 4 sides of the
      cadavers the procedure was feasible. In all cadavers, it was necessary to
      extensively drill the temporo-mandibular joint and to calibrate the external ear
      canal to allow adequate room to manoeuver the instruments and optics and to
      comfortably access the cerebellopontine angle. In addition, thorough
      skeletonisation of the carotid artery and the jugular bulb were necessary for the
      same purpose. In conclusion, ExpTTA appeared to be successful to access the
      internal auditory canal and cerebellopontine angle region. Potential extensive
      and routine application of this type of approach in lateral skull base surgery
      will depend on the development of technology and surgical refinements and on the
      diffusion of skull base endoscopic skills among otolaryngologists and
      neurosurgical community.

PMID- 28516967
TI  - Body-worn triaxial accelerometer coherence and reliability related to static
      posturography in unilateral vestibular failure.
AB  - Since changes in vestibular function may be one cause of disequilibrium, major
      advances in measuring postural control and sensory integration in vestibular
      impairments have been achieved by using posturography. However, in order to
      overcome problems related to this type of technology, body-worn accelerometers
      (ACC) have been proposed as a portable, low-cost alternative to posturography for
      measurements of postural sway in a friendly and ecologic environment. Due to the
      fact that no study to date has shown the experimental validity of ACC-based
      measures of body sway with respect to posturography for subjects with vestibular
      deficits, the aim of the present study was: i) to develop and validate a
      practical tool that can allow clinicians to measure postural sway derangements in
      an otoneurological setting by ACC, and ii) to provide reliable, sensitive and
      accurate automatic analysis of sway that could help in discriminating unilateral
      vestibular failure (UVF) patients. Thus, a group of 13 patients (seven females, 6
      males; mean age 48.6 +/- 6.4 years) affected for at least 6 months by UVF and 13
      matched healthy subjects were instructed to maintain an upright position during a
      static forceplate-based posturography (FBP) acquisition while wearing a Movit(r)
      sensor (by Captiks) with 3-D accelerometers mounted on the posterior trunk near
      the body centre of mass. Pearson product moment correlation demonstrated a high
      level of correspondence of four time-domain and three frequency-domain measures
      extracted by ACC and FBP testing; in addition, t-test demonstrated that two ACC
      based time- and frequency-domain parameters were reliable measures in
      discriminating UVF subjects. These aspects, overall, should further highlight the
      attention of clinicians and researchers to this kind of sway recording technique
      in the field of otoneurological disorders by considering the possibility to
      enrich the amount of quantitative and qualitative information useful for
      discrimination, diagnosis and treatment of UVF. In conclusion, we believe the
      present ACC-based measurement of sway offers a patient-friendly, reliable,
      inexpensive and efficient alternative recording technique that is useful -
      together with clinical balance and mobility tests - in various circumstances, as
      well as in outcome studies involving diagnosis, follow-up and rehabilitation of
      UVF patients.

PMID- 28516968
TI  - Preliminary experience with 4K ultra-high definition endoscope: analysis of pros
      and cons in skull base surgery.
AB  - During the last two decades endoscopic skull base surgery observed a continuous
      technical and technological development 3D endoscopy and ultra High Definition
      (HD) endoscopy have provided great advances in terms of visualisation and spatial
      resolution. Ultra-high definition (UHD) 4K systems, recently introduced in the
      clinical practice, will shape next steps forward especially in skull base surgery
      field. Patients were operated on through transnasal transsphenoidal endoscopic
      approaches performed using Olympus NBI 4K UHD endoscope with a 4 mm 0 degrees 
      Ultra Telescope, 300 W xenon lamp (CLV-S400) predisposed for narrow band imaging
      (NBI) technology connected through a camera head to a high-quality control unit
      (OTV-S400 - VISERA 4K UHD) (Olympus Corporation, Tokyo, Japan). Two screens are
      used, one 31" Monitor - (LMD-X310S) and one main ultra-HD 55" screen optimised
      for UHD image reproduction (LMD-X550S). In selected cases, we used a navigation
      system (Stealthstation S7, Medtronic, Minneapolis, MN, US). We evaluated 22
      pituitary adenomas (86.3% macroadenomas; 13.7% microadenomas). 50% were not
      functional (NF), 22.8% GH, 18.2% ACTH, 9% PRL-secreting. Three of 22 were
      recurrences. In 91% of cases we achieved total removal, while in 9% near total
      resection. A mean follow-up of 187 days and average length of hospitalisation was
      3.09 +/- 0.61 days. Surgical duration was 128.18+/- 30.74 minutes. We experienced
      only 1 case of intraoperative low flow fistula with no further complications.
      None of the cases required any post- or intraoperative blood transfusion. The
      visualisation and high resolution of the operative field provided a very detailed
      view of all anatomical structures and pathologies allowing an improvement in
      safety and efficacy of the surgical procedure. The operative time was similar to
      the standard 2D HD and 3D procedures and the physical strain was also comparable
      to others in terms of ergonomics and weight.

PMID- 28516969
TI  - Voluminous laryngeal schwannoma excision with a mini-invasive external approach:
      a case report.
AB  - Laryngeal schwannomas are extremely uncommon. We present a case of bulky
      supraglottic schwannoma with involvement of the preepiglottic and superior
      paraglottic spaces. Clinical findings, computed tomography and magnetic resonance
      images are presented. These characteristics are typical, however not specific to
      schwannomas. For definitive diagnosis, histology and immunohistochemistry are
      necessary. We present an external mini-invasive approach that allowed us to both
      obtain diagnosis and provide definitive treatment for this kind of voluminous
      laryngeal tumour.

PMID- 28516970
TI  - Diagnostic work-up in obstructive and inflammatory salivary gland disorders.
AB  - Inflammatory and obstructive disorders of the salivary glands are caused by very
      different pathological conditions affecting the gland tissue and/or the excretory
      system. The clinical setting is essential to address the appropriate diagnostic
      imaging work-up. According to history and physical examination, four main
      clinical scenarios can be recognised: (1) acute generalised swelling of major
      salivary glands; (2) acute swelling of a single major salivary gland; (3) chronic
      generalised swelling of major salivary glands, associated or not with "dry
      mouth"; (4) chronic or prolonged swelling of a single major salivary gland. The
      algorithm for imaging salivary glands depends on the scenario with which the
      patient presents to the clinician. Imaging is essential to confirm clinical
      diagnosis, define the extent of the disease and identify complications. Imaging
      techniques include ultrasound (US), computed tomography (CT) and magnetic
      resonance (MR) with MR sialography.

PMID- 28516971
TI  - Salivary biomarkers and proteomics: future diagnostic and clinical utilities.
AB  - Saliva testing is a non-invasive and inexpensive test that can serve as a source
      of information useful for diagnosis of disease. As we enter the era of genomic
      technologies and -omic research, collection of saliva has increased. Recent
      proteomic platforms have analysed the human salivary proteome and characterised
      about 3000 differentially expressed proteins and peptides: in saliva, more than
      90% of proteins in weight are derived from the secretion of three couples of
      "major" glands; all the other components are derived from minor glands, gingival
      crevicular fluid, mucosal exudates and oral microflora. The most common aim of
      proteomic analysis is to discriminate between physiological and pathological
      conditions. A proteomic protocol to analyze the whole saliva proteome is not
      currently available. It is possible distinguish two type of proteomic platforms:
      top-down proteomics investigates intact naturally-occurring structure of a
      protein under examination; bottom-up proteomics analyses peptide fragments after
      pre-digestion (typically with trypsin). Because of this heterogeneity, many
      different biomarkers may be proposed for the same pathology. The salivary
      proteome has been characterised in several diseases: oral squamous cell carcinoma
      and oral leukoplakia, chronic graft-versus-host disease Sjogren's syndrome and
      other autoimmune disorders such as SAPHO, schizophrenia and bipolar disorder, and
      genetic diseases like Down's Syndrome and Wilson disease. The results of research
      reported herein suggest that in the near future human saliva will be a relevant
      diagnostic fluid for clinical diagnosis and prognosis.

PMID- 28516972
TI  - Sialendoscopy for salivary stones: principles, technical skills and therapeutic
      experience.
AB  - Obstructive sialadenitis is the most common non-neoplastic disease of the
      salivary glands, and sialendoscopy is increasingly used in both diagnosis and
      treatment, associated in selected cases with endoscopic laser lithotripsy.
      Sialendoscopy is also used for combined minimally invasive external and
      endoscopic approaches in patients with larger and proximal stones that would
      require excessively long laser procedures. The present paper reports on the
      technical experience from the Ear, Nose and Throat Unit of the Sant'Orsola
      Malpighi Hospital of Bologna, and from the Department of Otorhinolaryngology of
      the University Hospital of Cagliari, Italy, including the retrospective analysis
      of the endoscopic and endoscopic assisted procedures performed on 48 patients (26
      females and 22 males; median age 45.3; range 8-83 years) treated for chronic
      obstructive sialadenitis at the University Hospital of Cagliari from November
      2010 to April 2016. The results from the Sant'Orsola-Malpighi Hospital of Bologna
      have been previously published. The technical aspects of sialendoscopy are
      carefully described. The retrospective analysis of the University Hospital of
      Cagliari shows that the disease was unilateral in 40 patients and bilateral in 8;
      a total of 56 major salivary glands were treated (22 submandibular glands and 34
      parotids). Five patients underwent bilateral sialendoscopy for juvenile recurrent
      parotitis. 10 patients were treated for non-lithiasic obstructive disease. In 33
      patients (68.75%) the obstruction was caused by salivary stones (bilateral
      parotid lithiasis in 1 case). Only 8 patients needed a sialectomy (5
      submandibular glands and 3 parotids). The conservative approach to obstructive
      sialadenitis is feasible and can be performed either purely endoscopically or in
      a combined modality, with a high percentage of success. The procedure must be
      performed with dedicated instrumentation by a skilled surgeon after proper
      training since minor to major complications can be encountered. Sialectomy should
      be the "extrema ratio" after failure of a conservative approach.

PMID- 28516974
TI  - Sialendoscope-assisted transoral removal of hilo-parenchymal sub-mandibular
      stones: surgical results and subjective scores.
AB  - It has been suggested that a conservative trans-oral approach to proximal and
      hilo-parenchymal submandibular stones (HPSMS) is a valid alternative to the more
      frequently used sialadenectomy. The aim of this study was to evaluate the
      surgical, ultrasonographic and patients' subjective outcomes of results of the
      trans-oral removal of HPSMS. Between January 2003 and September 2015,
      sialendoscope-assisted trans-oral surgery was used to remove symptomatic, large
      (> 7 mm), fixed and palpable HPSMS from 479 patients under general anaesthesia.
      All patients were followed clinically and ultrasonographically to investigate
      symptom relief and recurrence of stones, and were telephonically interviewed to
      assess saliva-related subjective outcomes with a questionnaire. Stones were
      successfully removed from 472 patients (98.5%); the seven failures (1.5%)
      concerned pure parenchymal stones. One year after the procedure, 408 patients
      (85.1%) were symptom free, 59 (12.3%) had recurrent obstructive symptoms and 12
      (2.6%) had recurrent infections. Of the 54 patients who developed a recurrent
      stone (11.2%), 52 underwent a second procedure: 29 interventional
      sialendoscopies, two sialendoscope-assisted intra-corporeal pneumatic
      lithotripsy, eight secondary transoral surgery to remove residual stones, six a
      cycle of extra-corporeal lithotripsy and seven submandibular sialadenectomy. Most
      patients (75.2%) reported mild surgery-related pain. The symptoms of 454 patients
      (94.8%) improved after adjunctive treatment and, at the end of follow-up, the
      affected gland was preserved in 98.5% of patients. A sialendoscope-assisted trans
      oral removal of large HPSMS is a safe, effective, conservative surgical
      procedure, and functional preservation of the main duct and parenchyma of the
      obstructed gland allows sialendoscopic access through the natural ostium in case
      of recurrence. Combining a trans-oral approach with other minimally invasive,
      conservative procedures ensures symptomatic relief and salivary duct system
      clearance in the majority of patients.

PMID- 28516973
TI  - Salivary lithotripsy in the era of sialendoscopy.
AB  - The traditional management of obstructive salivary disorders has been replaced by
      minimally-invasive gland-preserving techniques including shock-wave lithotripsy,
      sialendoscopy, interventional radiology and endoscopically video-assisted trans
      oral and cervical stone retrieval, of which sialendoscopy is considered to be the
      method of first choice. Primary endoscopically controlled stone extraction
      without prior fragmentation is only possible in 15-20% of cases; in more than
      80%, fragmentation is necessary because of the size, impactation and location of
      the stone, or an alternative treatment such as transoral duct surgery or combined
      approaches are required. Moreover, about 10-20% of all stones cannot be
      adequately accessed by means of a sialendoscope or any alternative surgical
      method and, in such cases, extra-corporeal shock wave lithotripsy (ESWL) is the
      treatment of choice. However, in endoscopically accessible stones, ESWL is being
      gradually replaced by endoscopically assisted intra-corporeal techniques,
      including endoscopically guided laser and pneumatic intracorporeal lithotripsy.
      We describe the currently most widely used techniques for salivary lithotripsy,
      including ESWL, and endoscopically guided laser, electrohydraulic, electrokinetic
      and pneumatic intra-corporeal lithotripsy, and discuss their indications given
      the widespread use of advanced rehabilitative sialendoscopy and combined
      therapeutic approaches.

PMID- 28516975
TI  - Sialendoscopy-assisted transfacial removal of parotid calculi.
AB  - Superficial parotidectomy has significant morbidity, and minimally invasive
      techniques have therefore been developed, including those involving
      sialendoscopy, to remove sialoliths and preserve the gland along with its
      function. The size, mobility and location of the sialolith, alongside the
      presence of strictures, all dictate management. We outline basic treatment
      paradigms and describe two sialoendoscopyassisted surgical procedures developed
      for treating stones, one intraoral and one extraoral.

PMID- 28516976
TI  - Salivary duct stenosis: diagnosis and treatment.
AB  - The management of stenoses of the major salivary glands had undergone a
      significant change during the last 15-20 years. Accurate diagnosis forms the
      basis of adapted minimal invasive therapy. Conventional sialography and MR
      sialography are useful examination tools, and ultrasound seems to be a first-line
      investigational tool if salivary duct stenosis is suspected as cause of gland
      obstruction. Sialendoscopy is the best choice to establish final diagnosis and
      characterise the stenosis in order to plan accurate treatment. In all major
      salivary glands, inflammatory stenosis can be distinguished from fibrotic
      stenosis. In the parotid duct system, an additional stenosis associated with
      various abnormalities of the duct system has been reported. Conservative therapy
      is not sufficient in the majority of cases. The development of a minimally
      invasive treatment regime, in which sialendoscopy plays a major role, has made
      the preservation of the gland and its function possible in over 90% of cases.
      Ductal incision procedures are the most important measure in submandibular duct
      stenoses, but sialendoscopy becomes more important in the more centrally located
      stenoses. Sialendoscopic controlled opening and dilation is the dominating method
      in parotid duct stenoses. In 10-15% of cases, success can be achieved after a
      combined treatment regime had been applied. This review article aims to give an
      overview on the epidemiology, diagnostics and current state of the art of the
      treatment of salivary duct stenoses.

PMID- 28516977
TI  - Complications of traditional and modern therapeutic salivary approaches.
AB  - The morbidity following traditional surgery of the salivary glands is well
      documented and includes postsurgical complications such as the Frey's syndrome,
      complete or partial facial nerve damage, facial scarring, greater auricular nerve
      numbness, sialocoeles and salivary fistula. The avulsion of the salivary duct,
      secondary strictures, gland swelling, salivary fistulas and perforations (false
      rout), traumatic ranulas, and the lingual nerve paraesthesia are the main
      endoscopy-related complications. In general, the rate of postsurgical
      complications after modern advanced minimally invasive surgical interventions is
      significantly lower compared with traditional surgery of the salivary glands.
      However, such comparisons cannot be performed because up-to-date traditional and
      minimally invasive surgical techniques are applied to different salivary
      disorders. Combinations of various minimally invasive techniques are also
      possible. There is no clear borderline between "traditional" and "modern" surgery
      of the salivary glands. It is appropriate to write about gradual replacement of
      old techniques with newer ones, and this process has no traffic lights.

PMID- 28516979
TI  - Interventional sialendoscopy for radioiodine-induced sialadenitis: quo vadis?
AB  - Salivary gland toxicity is a common adverse effect of radioactive iodine (131I)
      for the treatment of thyroid cancers with a prevalence ranging from 2% to 67% of
      the 131I exposed population. Recently, sialendoscopy has been introduced as an
      attractive diagnostic and therapeutic tool for management of patients with
      radioiodine-induced sialadenitis that is unresponsive to standard medical
      treatments. The objective of the current review was to assess the impact of this
      procedure on outcomes in patients suffering from radioiodine sialadenitis.
      Overall, eight studies were included and 122 patients underwent 264
      sialendoscopic procedures. Duct stenosis and mucous plugs were observed in 85.7%
      of endoscopic findings, supporting the role of ductal obstruction in the
      pathophysiology of radioiodine sialadenitis. In total, 89.3% of patients
      experienced complete or partial resolution of sialadenitis recurrences without
      any major adverse events, and parotidectomy was advocated in only 1 case.
      However, outcomes mainly concerned subjective reports and only two clinical
      experiences evaluated objective measurement with dissimilar results. Limited to
      few studies, xerostomia and obstructive symptoms responded differently after
      sialendoscopy. The optimal timing of salivary gland videoendoscopy needs to be
      further analysed in order to define the best management of radioiodine-induced
      obstructive sialadenitis.

PMID- 28516978
TI  - Sialendoscopic management of autoimmune sialadenitis: a review of literature.
AB  - Autoimmune diseases of major salivary glands include Sjogren's syndrome and a
      complex of disorders classified as immunoglobulin G4-related diseases. These
      pathologies are characterised by an autoimmune reaction mediated by T-helper
      lymphocytes that targets the ducts of exocrine glands in Sjogren's syndrome and
      glandular parenchyma in immunoglobulin G4-related diseases. Immunoglobulin G4
      related diseases represent recently introduced multi-organ diseases that also
      involve the salivary glands. However, the morbid conditions once known as
      Mikulicz's disease and Kuttner's tumour were recently considered as two variants
      of immunoglobulin G4-related diseases affecting the major salivary glands (
      immunoglobulin G4-related sialadenitis). This review briefly summarises the
      pathogenesis and clinical features of autoimmune diseases of the major salivary
      glands, focusing on the diagnostic and therapeutic role of sialendoscopy.

PMID- 28516980
TI  - Modern management of paediatric obstructive salivary disorders: long-term
      clinical experience.
AB  - Recent technological improvements in head and neck field have changed diagnostic
      and therapeutic strategies for salivary disorders. Diagnosis is now based on
      colour Doppler ultrasonography (US), magnetic resonance (MR) sialography and cone
      beam 3D computed tomography (CT), and extra- and intracorporeal lithotripsy,
      interventional sialendscopy and sialendoscopy-assisted surgery are used as
      minimally invasive, conservative procedures for functional preservation of the
      affected gland. We evaluated the results of our long-term experience in the
      management of paediatric obstructive salivary disorders. The study involved a
      consecutive series of 66 children (38 females) whose obstructive salivary
      symptoms caused by juvenile recurrent parotitis (JRP) (n = 32), stones (n = 20),
      ranula (n = 9) and ductal stenosis (n = 5). 45 patients underwent interventional
      sialendoscopy for JRP, stones and stenoses, 12 a cycle of extracorporeal
      shockwave lithotripsy (ESWL), three sialendoscopy-assisted transoral surgery, one
      drainage, six marsupialisation, and two suturing of a ranula. Three children
      underwent combined ESWL and interventional sialendoscopy, and seven a secondary
      procedure. An overall successful result was obtained in 90.9% of cases. None of
      the patients underwent traditional invasive sialadenectomy notwithstanding
      persistence of mild obstructive symptoms in six patients. No major complications
      were observed. Using a diagnostic work-up based on colour Doppler US, MR
      sialography and cone beam 3D TC, children with obstructive salivary disorders can
      be effectively treated in a modern minimally-invasive manner by extracorporeal
      and intracorporeal lithotripsy, interventional sialendoscopy and sialendoscopy
      assisted transoral surgery; this approach guarantees a successful result in most
      patients, thus avoiding the need for invasive sialadenectomy while functionally
      preserving the gland.

PMID- 28516982
TI  - Colorimetric and electrochemical quantification of global DNA methylation using a
      methyl cytosine-specific antibody.
AB  - We report a simple colorimetric (naked-eye) and electrochemical method for the
      rapid, sensitive and specific quantification of global methylation levels using
      only 25 ng of input DNA. Our approach utilises a three-step strategy; (i) initial
      adsorption of the extracted, purified and denatured bisulfite-treated DNA on a
      screen-printed gold electrode (SPE-Au), (ii) immuno-recognition of methylated DNA
      using a horseradish peroxidase (HRP)-conjugated methylcytosine (HRP-5mC) antibody
      and (iii) subsequent colorimetric detection by the enzymatic oxidation of
      3,3',5,5'-tetramethylbenzidin (TMB)/H2O2 which generated a blue-coloured product
      in the presence of methylated DNA and HRP-5mC immunocomplex. As TMB(ox) is
      electroactive, it also produces detectable amperometric current at +150 mV versus
      a Ag pseudo-reference electrode (electrochemical detection). The assay could
      successfully differentiate 5-aza-2'-deoxycytidine drug-treated and untreated
      Jurkat DNA samples. It showed good reproducibility (relative standard deviation
      (% RSD) = <5%, for n = 3) with fairly good sensitivity (as low as 5% difference
      in methylation levels) and specificity while analysing various levels of global
      DNA methylation in synthetic samples and cell lines. The method has also been
      tested for analysing the methylation level in fresh tissue samples collected from
      eight patients with oesophageal squamous cell carcinoma. We believe that this
      assay could be potentially useful as a low-cost alternative for genome-wide DNA
      methylation analysis in point-of-care applications.

PMID- 28516981
TI  - Botulinum toxin therapy: functional silencing of salivary disorders.
AB  - Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum,
      an anaerobic bacterium. BTX therapy is a safe and effective treatment when used
      for functional silencing of the salivary glands in disorders such as sialoceles
      and salivary fistulae that may have a post-traumatic or post-operative origin.
      BTX injections can be considered in sialoceles and salivary fistulae after the
      failure of or together with conservative treatments (e.g. antibiotics, pressure
      dressings, or serial aspirations). BTX treatment has a promising role in chronic
      sialadenitis. BTX therapy is highly successful in the treatment of gustatory
      sweating (Frey's syndrome), and could be considered the gold standard treatment
      for this neurological disorder.

PMID- 28516985
TI  - Gate-controlled heat generation in ZnO nanowire FETs.
AB  - Nanoscale heating production using nanowires has been shown to be particularly
      attractive for a number of applications including nanostructure growth, localized
      doping, transparent heating and sensing. However, all proof-of-concept devices
      proposed so far relied on the use of highly conductive nanomaterials, typically
      metals or highly doped semiconductors. In this article, we demonstrate a novel
      nanoheater architecture based on a single semiconductor nanowire field-effect
      transistor (NW-FET). Nominally undoped ZnO nanowires were incorporated into three
      terminal devices whereby control of the nanowire temperature at a given source
      drain bias was achieved by additional charge carriers capacitatively induced via
      the third gate electrode. Joule-heating selective ablation of poly(methyl
      methacrylate) deposited on ZnO nanowires was shown, demonstrating the ability of
      the proposed NW-FET configuration to enhance by more than one order of magnitude
      the temperature of a ZnO nanowire, compared to traditional two-terminal
      configurations. These findings demonstrate the potential of field-effect
      architectures to improve Joule heating power in nanowires, thus vastly expanding
      the range of suitable materials and applications for nanowire-based nanoheaters.

PMID- 28516984
TI  - Cadmium transfer from contaminated soils to the human body through rice
      consumption in southern Jiangsu Province, China.
AB  - Consumption of crops grown in cadmium-contaminated soils is an important Cd
      exposure route to humans. The present study utilizes statistical analysis and in
      vitro digestion experiments to uncover the transfer processes of Cd from soils to
      the human body through rice consumption. Here, a model was created to predict the
      levels of bioaccessible Cd in rice grains using phytoavailable Cd quantities in
      the soil. During the in vitro digestion, a relatively constant ratio between the
      total and bioaccessible Cd in rice was observed. About 14.89% of Cd in soils was
      found to be transferred into rice grains and up to 3.19% could be transferred
      from rice grains to the human body. This model was able to sufficiently predict
      rice grain cadmium concentrations based on CaCl2 extracted zinc and cadmium
      concentrations in soils (R2 = 0.862). The bioaccessible Cd concentration in rice
      grains was also able to be predicted using CaCl2 extracted cadmium from soil (R2
      = 0.892). The models established in this study demonstrated that CaCl2 is a
      suitable indicator of total rice Cd concentrations and bioaccessible rice grain
      Cd concentrations. The chain model approach proposed in this study can be used
      for the fast and accurate evaluation of human Cd exposure through rice
      consumption based on the soil conditions in contaminated regions.

PMID- 28516986
TI  - Single-layer MoS2 formation by sulfidation of molybdenum oxides in different
      oxidation states on Au(111).
AB  - The sulfidation of a MoO3 precursor into MoS2 is an important step in the
      preparation of catalysts for the hydrodesulfurization process that is widely
      utilized in oil refineries. Molybdenum oxides are also the most commonly used
      precursors for MoS2 growth in, e.g., the synthesis of novel two-dimensional
      materials. In the present study, we investigate the transformation of MoOx into
      MoS2 on a model Au(111) surface through sulfidation in H2S gas atmosphere using
      in situ scanning tunneling microscopy and X-ray photoemission spectroscopy. We
      find that progressive annealing steps of physical vapor deposited MoO3 powder
      allow us to control the stoichiometry and oxidation state of the precursor oxide.
      Subsequently, we investigate the sulfidation of the compounds ranging from pure
      low-oxygen Mo to fully oxidized MoO3 oxide sulfidation using two different
      methods. We find that the prerequisite for the efficient formation of MoS2 is
      that Mo stays in the highest Mo6+ state before sulfidation, whereas the presence
      of the reduced MoOx phase impedes the MoS2 growth. We also find that it is more
      efficient to form MoS2 by post-sulfidation of MoOx rather than its reactive
      deposition in H2S gas, which leads to rather stable amorphous oxysulfide phases.

PMID- 28516987
TI  - Theoretical investigations into the charge transfer properties of thiophene alpha
      substituted naphthodithiophene diimides: excellent n-channel and ambipolar
      organic semiconductors.
AB  - A theoretical study was carried out to investigate the electronic structures and
      the charge transport properties of a series of naphthodithiophene diimide (NDTI)
      thiophene alpha-substituted derivatives NDTI-X using density functional theory
      and classical Marcus charge transfer theory. This study deeply revealed the
      structure-property relationships by analyzing the intermolecular interactions in
      crystal structures of C8-NDTI and C8-NDTI-Cl thoroughly by using the Hirshfeld
      surface, QTAIM theories and symmetry-adapted perturbation theory (SAPT). Our
      results suggested that a 2-D brick-like pi-stacking structure makes C8-NDTI-Cl a
      more excellent n-type semiconducting material with MUmax-e of 2.554 cm2 V-1 s-1
      than C8-NDTI with a herringbone-like slipped pi-stacking motif. In addition, the
      calculated results showed that by modifying the thiophene alpha-positions of NDTI
      with electron-withdrawing substituents, -F, -Cl and -CN, low-lying LUMO energy
      levels and a high adiabatic electron affinity EA(a) can be obtained; while
      introducing electron-donating groups, benzene (-B), thiophene (-T),
      benzo[b]thiophene (-BT) and naphtha[2,3-b]thiophene (-NT), expanded the molecular
      pi-conjugated backbone, and narrow band gaps, high EA(a) and small reorganization
      energies can be obtained. Theoretical simulations predict that NDTI-CN is an
      excellent air-stable n-type organic semiconducting material with an average
      electron mobility MUe of up to 1.743 cm2 V-1 s-1. Owing to their high EA(a),
      moderate adiabatic ionization potential IP(a) as well as small hole and electron
      reorganization energies, NDTI-BT and NDTI-NT are two well-balanced air-stable
      ambipolar semiconducting materials. The theoretical average hole/electron
      mobilities are as high as 2.708/3.739 cm2 V-1 s-1 for C8-NDTI-NT and 1.597/2.350
      cm2 V-1 s-1 for C8-NDTI-BT, respectively.

PMID- 28516989
TI  - The effect of anions on the electrochemical properties of polyaniline for
      supercapacitors.
AB  - To investigate the effect of anions on the electrochemical properties of
      polyaniline (PANI) for supercapacitors, electrochemical performance tests of PANI
      with different dopant anions were carried out in the corresponding acid solutions
      by cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) methods. In
      particular, ionic fluxes and solvent molecules involved in redox processes can be
      analyzed by the electrochemical quartz crystal microbalance (EQCM) technique and
      discriminated by simultaneously recording cyclic voltammograms and mass changes
      during redox switching. The emeraldine base (EB) form of PANI prepared in a
      protonic acid with bigger anions can be easily doped by a protonic acid with
      smaller anions, and conversely, PANI-EB is hard to be doped. The anodic reversal
      potential of potentiodynamic cycling heavily influences the electrochemical
      stability of PANI. High anodic potentials result in PANI degradation. Its
      supercapacitive properties including specific capacitance, power density and
      cycling stability are strongly dependent upon the type of dopant anion. PANI with
      the dopant anions of oxalic acid has the highest specific capacitance and the
      best cycling stability among the used acids. The diffusion coefficient of anions
      plays a key role in determining power density. PANI films with organic dopant
      anions exhibit better cycling stability than their inorganic counterparts. It is
      believed that the hydrolysis of PANI facilitated by the additional water
      molecules accompanied by dopant anions into and out of the PANI matrix is a key
      factor responsible for the cycling instability.

PMID- 28516988
TI  - Syntheses and catalytic oxotransfer activities of oxo molybdenum(vi) complexes of
      a new aminoalcohol phenolate ligand.
AB  - The new aminoalcohol phenol 2,4-di-tert-butyl-6-(((2-hydroxy-2
      phenylethyl)amino)methyl)phenol (H2L) was prepared by a facile solvent-free
      synthesis and used as a tridentate ligand for new cis-dioxomolybdenum(vi)(L)
      complexes. In the presence of a coordinating solvent (DMSO, MeOH, pyridine), the
      complexes crystallise as monomeric solvent adducts while in the absence of such
      molecules, a trimer with asymmetric Mo[double bond, length as m-dash]O->Mo
      bridges crystallises. The complexes can catalyse epoxidation of cis-cyclooctene
      and sulfoxidation of methyl-p-tolylsulfide, using tert-butyl hydroperoxide as
      oxidant.

PMID- 28516990
TI  - Cross talk between neurometals and amyloidogenic proteins at the synapse and the
      pathogenesis of neurodegenerative diseases.
AB  - Increasing evidence suggests that disruption of metal homeostasis contributes to
      the pathogenesis of various neurodegenerative diseases, including Alzheimer's
      disease, prion diseases, Lewy body diseases, and vascular dementia.
      Conformational changes of disease-related proteins (amyloidogenic proteins), such
      as beta-amyloid protein, prion proteins, and alpha-synuclein, are well
      established contributors to neurotoxicity and to the pathogenesis of these
      diseases. Recent studies have demonstrated that these amyloidogenic proteins are
      metalloproteins that bind trace elements, including zinc, iron, copper, and
      manganese, and play significant roles in the maintenance of metal homeostasis. We
      present a current review of the role of trace elements in the functions and
      toxicity of amyloidogenic proteins, and propose a hypothesis integrating metal
      homeostasis and the pathogenesis of neurodegenerative diseases that is focused on
      the interactions among metals and between metals and amyloidogenic proteins at
      the synapse, considering that these amyloidogenic proteins and metals are co
      localized at the synapse.

PMID- 28516992
TI  - A nano silver-xerogel (Ag nps@modified TEOS) as a newly developed nanocatalyst in
      the synthesis of benzopyranopyrimidines (with secondary and primary amines) and
      gem-bisamides.
AB  - Silver nanoparticles have been prepared from a chemical reduction approach and
      supported on modified TEOS (tetraethylorthosilicate) xerogels to be studied as a
      nanocatalyst in the conversions of benzopyranopyrimidines (with primary as well
      as secondary amines along with the mechanism by trapping the imine intermediate)
      and also in the synthesis of gem-bisamides. Different conditions for the
      performance of the nanocatalyst have been screened and tolerance with respect to
      variable functionalities has been observed, resulting in excellent yields; and
      confirmation of products synthesized has been done using studies like 1H NMR, 13C
      NMR and mass analysis. Also, SEM-EDX and TEM of the nanocatalyst have been
      performed to know the internal and external morphology, size and elemental
      composition. UV and XRD analysis to confirm the silver nanoparticles' and
      xerogel's presence, TGA to study the thermal stability and FTIR to study the
      modification pattern of the nanocatalyst have been undertaken and presented in
      this work.

PMID- 28516991
TI  - Synthesis, properties, and crystal structures of pi-extended double [6]helicenes:
      contorted multi-dimensional stacking lattice.
AB  - The synthesis and properties of a new pi-extended double [6]helicene 2 and a
      dithia[6]helicene 3 are described. Compared to the previously reported parent
      double-helicene molecule 1, the introduction of n-butyl groups successfully
      improved the solubility, which allowed an experimental investigation into the
      electronic structure of 2 and 3 by photophysical measurements and cyclic
      voltammetry. The characteristic two-blade propeller structures of 2 and 3 were
      unambiguously determined by single-crystal X-ray diffraction analysis. The
      crystal packing structure of 2 exhibited a contorted two-dimensional stacking,
      whereby molecules of n-pentane were incorporated in the stacks. Despite the
      presence of n-butyl groups, 3 formed a unique three-dimensional stacking lattice
      in the crystal. Time-resolved microwave conductivity measurements revealed that
      the double helicenes (1-3) exhibited transient conductivities. An organic field
      effect transistor fabricated using 3 was found to function as a p-type
      transistor.

PMID- 28516993
TI  - Stable and conductive lead halide perovskites facilitated by X-type ligands.
AB  - Lead halide perovskites exhibit outstanding optoelectronic and optical
      properties. However, some applications of perovskites are hindered by their
      instability in polar environments; thus, how to balance stability with
      conductivity is a great challenge. Here, we report a new approach of using X-type
      ligands to address this issue. Surface treatments containing multi-step ligand
      exchanges and ion filling were necessary to obtain X-type ligand-protected
      perovskites. Performances of this material show that: (1) the crystal structure
      of perovskites is stable in ethanol; (2) surface defects can be fixed by a
      photoactivation process and photoluminescence intensity can be enhanced to 136%;
      and (3) electronic devices fabricated from such materials show stabilility even
      after washing with ethanol. X-type ligand-protected perovskites with high
      stability and good conductivity are promising new materials for wide applications
      in electronic and optoelectronics devices.

PMID- 28516983
TI  - Nanoparticle design strategies for enhanced anticancer therapy by exploiting the
      tumour microenvironment.
AB  - Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites.
      Compared with normal tissue, the tumour microenvironment has some unique
      properties, such as vascular abnormalities, hypoxia and acidic pH. There are many
      types of cells, including tumour cells, macrophages, immune and fibroblast cells,
      fed by defective blood vessels in the solid tumour. Exploiting the tumour
      microenvironment can benefit the design of nanoparticles for enhanced therapeutic
      effectiveness. In this review article, we summarized the recent progress in
      various nanoformulations for cancer therapy, with a special emphasis on tumour
      microenvironment stimuli-responsive ones. Numerous tumour microenvironment
      modulation strategies with promising cancer therapeutic efficacy have also been
      highlighted. Future challenges and opportunities of design consideration are also
      discussed in detail. We believe that these tumour microenvironment modulation
      strategies offer a good chance for the practical translation of nanoparticle
      formulas into clinic.

PMID- 28516994
TI  - 3D ordered porous MoxC (x = 1 or 2) for advanced hydrogen evolution and Li
      storage.
AB  - 3D ordered porous structures of MoxC are prepared with different Mo to C ratios
      and tested for two possible promising applications: hydrogen evolution reaction
      (HER) through water splitting and lithium ion batteries (LIBs). Mo2C and MoC with
      3D periodic ordered structures are prepared with a similar process but different
      precursors. The 3D ordered porous MoC exhibits excellent cycling stability and
      rate performance as an anode material for LIBs. A discharge capacity of 450.9 mA
      h g-1 is maintained up to 3000 cycles at 10.0 A g-1. The Mo2C with a similar
      ordered porous structure shows impressive electrocatalytic activity for the HER
      in neutral, alkaline and acidic pH solutions. In particular, Mo2C shows an onset
      potential of only 33 mV versus a reversible hydrogen electrode (RHE) and a Tafel
      slope of 42.5 mV dec-1 in a neutral aqueous solution (1.0 M phosphate buffer
      solution), which is approaching that of the commercial Pt/C catalyst.

PMID- 28516995
TI  - Regioselective 6-endo-dig iodocyclization: an accessible approach for iodo
      benzo[a]phenazines.
AB  - A facile approach for the synthesis of substituted iodo-benzo[a]phenazines from 2
      aryl-3-(aryl/alkylethynyl)quinoxalines via 6-endo-dig ring closure has been
      described under mild reaction conditions. Iodocyclization proceeds through the
      iodonium ion intermediate followed by nucleophilic cyclization with the C-H bond
      of the arene. Furthermore, the resulting 6-iodo-5-aryl/alkyl benzo[a]phenazine
      derivatives allowed for structural diversification by employing various coupling
      reactions. The structure of iodo-benzo[a]phenazine was confirmed by X-ray
      crystallographic studies of the compound.

PMID- 28516996
TI  - Growth of two dimensional silica and aluminosilicate bilayers on Pd(111): from
      incommensurate to commensurate crystalline.
AB  - Two-dimensional (2D) silica (SiO2) and aluminosilicate (AlSi3O8) bilayers grown
      on Pd(111) were fabricated and systematically studied using ultrahigh vacuum
      surface analysis in combination with theoretical methods, including Auger
      electron spectroscopy, X-ray photoelectron spectroscopy, low-energy electron
      diffraction (LEED), scanning tunneling microscopy (STM), and density functional
      theory. Based on LEED results, both SiO2 and AlSi3O8 bilayers start ordering
      above 850 K in 2 * 10-6 Torr oxygen. Both bilayers show hexagonal LEED patterns
      with a periodicity approximately twice that of the Pd(111) surface. Importantly,
      the SiO2 bilayer forms an incommensurate crystalline structure whereas the
      AlSi3O8 bilayer crystallizes in a commensurate structure. The incommensurate
      crystalline SiO2 structure on Pd(111) resulted in a moire pattern observed with
      LEED and STM. Theoretical results show that straining the pure SiO2 bilayer to
      match Pd(111) would cost 0.492 eV per unit cell; this strain energy is reduced to
      just 0.126 eV per unit cell by replacing 25% of the Si with Al which softens the
      material and expands the unstrained lattice. Furthermore, the missing electron
      created by substituting Al3+ for Si4+ is supplied by Pd creating a chemical bond
      to the AlSi3O8 bilayer, whereas van der Waals interactions predominate for the
      SiO2 bilayer. The results reveal how the interplay between strain, doping, and
      charge transfer determine the structure of metal-supported 2D silicate bilayers
      and how these variables may potentially be exploited to manipulate 2D materials
      structures.

PMID- 28516998
TI  - Controllable design of tunable nanostructures inside metal-organic frameworks.
AB  - The controllable encapsulation of nanoentities (such as metal nanoparticles,
      quantum dots, polyoxometalates, organic and metallorganic molecules,
      biomacromolecules, and metal-organic polyhedra) into metal-organic frameworks
      (MOFs) to form composite materials has attracted significant research interest in
      a variety of fields. These composite materials not only exhibit the properties of
      both the nanoentities and the MOFs but also display unique and synergistic
      functionalities. Tuning the sizes, compositions, and shapes of nanoentities
      encapsulated in MOFs enables the final composites to exhibit superior performance
      to those of the separate constituents for various applications. In this tutorial
      review article, we summarized the state-of-the-art development of MOFs containing
      encapsulated tunable nanoentities, with special emphasis on the preparation and
      synergistic properties of these composites.

PMID- 28517001
TI  - Gold-catalyzed oxidative hydroacylation reactions of alpha-iminoalkynes with
      aldehydes and O2.
AB  - Gold-catalyzed aerobic oxidations of alpha-iminoalkynes with aryl aldehydes led
      to oxidative 1,3-hydroacyclation reactions, yielding high Z-selectivity. We
      performed 2H- and 18O-labeling experiments to confirm the role of water as an
      oxygen donor and O2 as the main oxidant. The Z-selectivity arises from an
      efficient conjugation between the enone and its aryl substituent. We postulate an
      initial [4+2]-annulation of alpha-iminoalkynes with aldehydes to form a six
      membered oxonium species that is attacked by water, followed by the O2 oxidation
      of a key intermediate.

PMID- 28516997
TI  - Peptide and antibody ligands for renal targeting: nanomedicine strategies for
      kidney disease.
AB  - The kidney is one of the body's main filtration organs, and hence, opportunity
      exists for designing nanomedicine that can naturally accumulate in the kidneys
      for renal diseases. In addition to traditional physiochemical properties for
      kidney accumulation, such as size and charge, synthesized nanoparticles can be
      conjugated with targeting ligands which further home the nanocarriers to cell
      types of interest. In this review, we highlight key studies that have shown
      success in utilizing peptide- or antibody-based ligands in nanoparticles to
      target the glomerulus, podocytes, or renal tubule cells in the kidney. In
      addition, other ligand candidates which have shown renal affinity, but have not
      yet been integrated into a nanoparticle are also presented. These studies can
      provide insight into the design of novel clinical solutions for improved
      detection, prevention, and treatment of renal diseases using nanomedicine
      efforts.

PMID- 28517002
TI  - Modulation of the FeII spin crossover effect in the pentadecanuclear
      {Fe9[M(CN)8]6} (M = Re, W) clusters by facial coordination of tridentate
      polyamine ligands.
AB  - Spin crossover (SCO) materials, revealing the externally tunable transition
      between two different spin states, arouse great scientific interest due to their
      perspective application in information storage, display devices and sensing. Of
      special importance are the molecular systems offering the possibility of
      multimodal switching within many spin centers. This is achievable in polynuclear
      clusters consisting of several SCO-active complexes, however, such molecules are
      very rare. Herein, we report a unique pair of nanometric pentadecanuclear
      {Fe9[M(CN)8]6(Me3tacn)8}.14MeOH (Me3tacn = 1,4,7-trimethyl-1,4,7
      triazacyclononane, M = Re, 1; M = W, 2) clusters exhibiting a thermally induced
      spin crossover effect on Fe(ii) complexes, that is on both central and external
      Fe sites embedded in the cyanido-bridged cluster core. The spin transition occurs
      gradually in the 120-300 K range, and it is not fully completed even at room
      temperature. We show that facial coordination of an N,N,N-tridentate Me3tacn
      ligand dramatically modifies the character of the spin transition phenomenon when
      confronted with the previously reported {Fe9[M(CN)8]6(MeOH)24}.nMeOH (M = Re, W)
      clusters by (i) engaging, for the first time, not only central but also external
      Fe intracluster units in the SCO effect, (ii) cancelling the Fe-W charge transfer
      pathway, and (iii) decreasing the cooperativity within the supramolecular
      network.

PMID- 28517003
TI  - Liquid phase epitaxial growth of heterostructured hierarchical MOF thin films.
AB  - Precise control of epitaxial growth of MOF-on-MOF thin films, for ordered
      hierarchical tbo-type structures is demonstrated. The heterostructured MOF thin
      film was fabricated by successful sequential deposition of layers from two
      different MOFs. The 2-periodic layers, edge-transitive 4,4-square lattices
      regarded as supermolecular building layers, were commendably cross-linked using a
      combination of inorganic/organic and organic pillars.

PMID- 28517004
TI  - Exploitation of new structurally diverse d-glucuronamide-containing N-glycosyl
      compounds: synthesis and anticancer potential.
AB  - The synthesis and anticancer evaluation of novel N-glycosyl derivatives
      containing N-substituted glucuronamide moieties, as nucleoside analogs or as
      prospective mimetics of glycosyl phosphates or of nucleotides, is reported. These
      compounds comprise N-anomerically-linked nucleobases or motifs that are
      surrogates of a phosphate group, such as sulfonamide or phosphoramidate moieties.
      1-Sulfonamido glucuronamides containing N-benzyl, N-propargyl or N-dodecyl
      carboxamide units were synthesized through glycosylation of methanesulfonamide
      with tetra-O-acetyl glucuronamides. 1-Azido glucuronamides were accessed by
      microwave-assisted reactions of tetra-O-acetyl glucuronamides with TMSN3 and were
      further converted into N-glycosylphosphoramidates by treatment with trimethyl
      phosphite. Potential glucuronamide-based nucleotide mimetics comprising both an
      anomeric sulfonamide/phosphoramidate group and a benzyltriazolylmethyl amide
      system at C-5, as nucleobase mimetics, were synthesized via 'click' cycloaddition
      of N-propargyl glucuronamide derivatives with benzyl azide. N-Dodecyl tetra-O
      acetyl glucuronamides were converted into uracil and purine nucleosides via N
      glycosylation of the corresponding silylated nucleobases. Biological screening
      revealed significant antiproliferative activities of the N-dodecyl glucuronamide
      containing sulfonamide, phosphoramidate and nucleosides in K562 and MCF-7 cells.
      The highest effect was exhibited by the N9-linked purine nucleoside in the breast
      cancer cell MCF-7 with a GI50 value similar to that of clinically used 5
      fluorouracil. Immunoblotting and cell cycle analysis of K562 cells treated with
      the most active compound as well as evaluation of the effect of this nucleoside
      on the activities of caspases 3 and 7 showed induction of apoptosis as the
      mechanism of cell death.

PMID- 28517005
TI  - Hydrophobic hydration and anomalous diffusion of elastin in an ethanolic
      solution.
AB  - Elastin is an important structural protein that confers elasticity to tissues. It
      is widely used in the biosynthesis of human elastic tissues and exhibits
      interesting properties. This study reports an insight into the unusual dispersion
      and anomalous diffusion of elastin in an ethanolic solution. Due to its complex
      hydrophobic structure, its dispersibility was found to be sensitive towards the
      hydrophobicity of the solvent. Electrophoresis measurements (zeta-potential data)
      revealed that its net polarity changed from an anionic to a cationic state with
      the decreasing solvent hydrophobicity (ethanol content in the solvent). An
      interesting transition temperature of ~297 K was observed above which the
      hydrophobic interactions among the protein molecules became dominant. Double
      layer repulsion between protein molecules competes with attractive hydrophobic
      interactions and causes molecular self-organization. A DLVO-based theoretical
      model showed that hydrophobic interactions were facilitated by a binary solvent
      (ethanol-water), and the repulsive double layer screening provided sufficient
      energy to overcome the interactions between hydrophobic domains in the protein
      molecule and allow the self-assembly to occur.

PMID- 28517006
TI  - Synthesis and characterization of a family of thioether-dithiolate-bridged
      heteronuclear iron complexes.
AB  - The thioether-dithiolate-bridged heterotrinuclear complexes [Cp*Fe(MU
      1k3SSS':2k2SS-tpdt)M(MU-2k2SS:3k3SSS'-tpdt)FeCp*][PF6]2 (Cp* = eta5-C5Me5; tpdt =
      S(CH2CH2S)2; 2, M = Co; 3, M = Ni; 4, M = Pd) have been prepared by a reaction of
      [Cp*Fe(eta3-tpdt)] (1) with complexes CoCl2, NiCl2(PPh3)2, and PdCl2(PPh3)2,
      respectively. Similarly, treatment of complex 1 with CuCl(PPh3) or AgPF6 afforded
      two heterotrinuclear complexes, [Cp*Fe(MU-1k3SSS':2k2SS-tpdt)M(MU-2k2SS:3k3SSS'
      tpdt)FeCp*][PF6] (5, M = Cu; 6, M = Ag), while reaction of 1 with the complex
      AuCl(PPh3) gave a heterobinuclear complex, [Cp*Fe(MU-1k3SSS':2k1S
      tpdt)Au(PPh3)][PF6] (7). These complexes have been spectroscopically and
      crystallographically characterized. An X-ray diffraction analysis showed that
      complexes 2, 3, 5, and 6 feature a heterometal center binding four sulfur atoms
      of two tpdt ligands with a cis orientation. However, in the Pd-containing complex
      4, two tpdt ligands are arranged in a trans configuration. The MUeff data and EPR
      results indicate that complexes 2, 4, 5, 6, and 7 are paramagnetic and only
      complex 3 is diamagnetic. Electrochemical experiments on these heteronuclear
      clusters were performed at room temperature. Discrepancy of the redox couples in
      the CV plots of these complexes indicates different one-electron transfer
      processes.

PMID- 28517007
TI  - Generation of a cell-permeable cycloheptapeptidyl inhibitor against the peptidyl
      prolyl isomerase Pin1.
AB  - Cyclic peptides are capable of binding and modulating challenging drug targets
      including protein-protein interactions. However, their lack of membrane
      permeability prevents their application against intracellular targets. In this
      study, we show that it is possible to design a cell-permeable and biologically
      active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl
      prolyl isomerase Pin1 by integrating cell-penetrating and target-binding
      sequences.

PMID- 28517008
TI  - Further insights into the kinetics of thermal decomposition during continuous
      cooling.
AB  - Following the previous work (Phys. Chem. Chem. Phys., 2016, 18, 32021), this
      study continues to investigate the intriguing phenomenon of thermal decomposition
      during continuous cooling. The phenomenon can be detected and its kinetics can be
      measured by means of thermogravimetric analysis (TGA). The kinetics of the
      thermal decomposition of ammonium nitrate (NH4NO3), nickel oxalate (NiC2O4), and
      lithium sulfate monohydrate (Li2SO4.H2O) have been measured upon heating and
      cooling and analyzed by means of the isoconversional methodology. The results
      have confirmed the hypothesis that the respective kinetics should be similar for
      single-step processes (NH4NO3 decomposition) but different for multi-step ones
      (NiC2O4 decomposition and Li2SO4.H2O dehydration). It has been discovered that
      the differences in the kinetics can be either quantitative or qualitative.
      Physical insights into the nature of the differences have been proposed.

PMID- 28517009
TI  - Stress-induced surface instabilities and defects in thin films sputter deposited
      on compliant substrates.
AB  - Existing analyses predict that thin metal films deposited on compliant substrates
      are subject to a variety of surface instabilities, such as wrinkles, folds,
      creases, etc., that become more prominent with increased compressive residual
      stress. Under compressive stress, cracks have been assumed to form only when the
      interfacial strength is weak, allowing the film to detach from the substrate. In
      this work, we demonstrate that cracks also form on surfaces under compressive
      mismatch strain when the interface is strong. In particular, we consider metal
      alloy films sputter deposited under bias on elastomers with different
      thicknesses, curing temperatures or surface treatments. The deposition parameters
      created residual compressive strains and strong adhesion in the bilayers. Samples
      without surface treatment formed wrinkles and through-thickness cracks at 0.25
      0.4% mismatch strains. Only through-thickness cracks were observed in UV treated
      samples. The crack spacing was found to decrease by a factor of 4 when the
      surface was UV treated and by a factor of 3 as the elastomer thickness decreased
      from 30 to 6 MUm. Cracks penetrated through the elastomer, 15-30 times deeper
      than the film thickness, and formed in all samples with a brittle coating. A
      numerical model was developed to explain the formation of through-thickness
      cracks and wrinkles under applied compressive mismatch strains. The model
      suggests that cracks can initiate from the peak of wrinkles when the critical
      fracture strength of the coating is exceeded. For the UV treated samples, through
      thickness cracks are possibly impacted by the formation of an embrittled near
      surface PDMS layer.

PMID- 28517010
TI  - Suppression of near band edge emission in specially engineered ZnO twin nanorods.
AB  - We report the synthesis of a unique zinc oxide nanorod structure in which an
      amorphous ZnO layer is sandwiched between two identical crystalline segments of
      ZnO. A simple hydrothermal reaction method was used for this purpose, which
      allowed us to tune the amorphous and crystalline sections of the nanorods via
      reaction temperature. A systematic study of the morphology and dimensions of the
      nanorods grown under various conditions was performed using a combination of
      scanning and transmission electron microscopy. Transmission electron microscopy
      (TEM) clearly showed an amorphous separation between the two crystalline
      segments. UV-vis absorption spectroscopy of the twin nanorods (TNRs) showed a
      redshift in the optical band gap as a function of the growth duration, indicating
      slightly stressed growth of the crystalline segments. For a longer growth
      duration, as the amorphous gap starts to get bridged by crystalline growth,
      redshift in optical band gap becomes constant. This confirms a true mechanical
      gap between the two crystalline segments of the nanorods. Temperature dependent
      photoluminescence (PL) spectra of the TNRs showed a variation in free exciton
      (FX) emission energy, which fitted very well to a model incorporating lattice
      dilation in addition to the standard electron-phonon interactions. At low
      temperatures (below ~180 K) we observed the appearance of visible emission peaks
      due to localization of defect levels. A loss in the near band edge emission
      intensity was observed at low temperatures, commensurate with the appearance of
      defect emission in the visible range.

PMID- 28517011
TI  - Dissection of H-bonding interactions in a glycolic acid-water dimer.
AB  - The binding strength and collective effects of multiple H-bonds in the glycolic
      acid-water dimer were studied in comparison to the aromatic analog, 9-hydroxy-9
      fluorene carboxylic acid (9HFCA). Quantitative analysis by the generalized Kohn
      Sham energy decomposition analysis shows that the energy difference in each
      specific physical interaction, from a glycolic acid-water dimer to a 9HFCA-water
      dimer, is small and amounts to less than 5% of the binding energy of the 9HFCA
      water dimer. Extensive comparison of further, similar H-bonded complexes with
      widely varying binding strengths reinforces their excellent analogy in that the
      fluorene group acts as a non-interfering spectator for intermolecular H-bonding
      interactions. With reference to the spectroscopic measurement on the 9HFCA-water
      dimer (8.51 +/- 0.09 kcal mol-1), the binding energy of the glycolic acid-water
      dimer is estimated to be 8.51 +/- 0.31 kcal mol-1, a much better accuracy than
      previous reports. Furthermore, correlating the infrared spectra of 9HFCA H-bonded
      complexes provides a circumstantial probing of the existence and consequences of
      cooperative and anti-cooperative behaviors in the glycolic acid-water dimer. Our
      studies point to the interesting H-bonding phenomena in the glycolic acid-water
      dimer, which may inspire challenging experiments in future.

PMID- 28517012
TI  - Re-characterization of hammerhead ribozymes as molecular tools for intermolecular
      RNA cleavage.
AB  - A new guideline for the construction of hammerhead ribozymes to achieve trans
      cleavage of a single-stranded RNA molecule was developed. The sequence rule of
      the HHRz cleavage site was highly recommended to be "DWH" with an optimal binding
      arm length of 8-9nt, which diverged from the former rule of "NUX".

PMID- 28517013
TI  - Incipient microphase separation in short chain perfluoropolyether-block
      poly(ethylene oxide) copolymers.
AB  - Incipient microphase separation is observed by wide angle X-ray scattering (WAXS)
      in short chain multiblock copolymers consisting of perfluoropolyether (PFPE) and
      poly(ethylene oxide) (PEO) segments. Two PFPE-PEO block copolymers were studied;
      one with dihydroxyl end groups and one with dimethyl carbonate end groups.
      Despite having a low degree of polymerization (N ~ 10), these materials exhibited
      significant scattering intensity, due to disordered concentration fluctuations
      between their PFPE-rich and PEO-rich domains. The disordered scattering intensity
      was fit to a model based on a multicomponent random phase approximation to
      determine the value of the interaction parameter, chi, and the radius of
      gyration, Rg. Over the temperature range 30-90  degrees C, the values of chi were
      determined to be very large (~2-2.5), indicating a high degree of immiscibility
      between the PFPE and PEO blocks. In PFPE-PEO, due to the large electron density
      contrast between the fluorinated and non-fluorinated block and the high value of
      chi, disordered scattering was detected at intermediate scattering angles, (q ~ 2
      nm-1) for relatively small polymer chains. Our ability to detect concentration
      fluctuations was enabled by both a relatively large value of chi and significant
      scattering contrast.

PMID- 28517014
TI  - N-Atom transfer via thermal or photolytic activation of a Co-azido complex with a
      PNP pincer ligand.
AB  - Thermal or photolytic activation of well-defined mononuclear [Co(N3)(PNP)] (PNP =
      2,2'-bis(diisopropylphosphino)-4,4'-ditolylamido) results in the structurally
      characterized dinuclear species [Co(MU-N;kappa3-P,N,N-PNPN)]2 (3), with two N
      bridging phosphiniminato bridgeheads. Density Functional Theory (DFT)
      calculations indicate the intermediacy of a mononuclear cobalt-nitrido complex,
      followed by N-migratory insertion into a Co-P bond. Reaction of 3 with two equiv.
      HCl leads to rupture of the dimer with formation of mononuclear [CoCl(PNPNH)] (4)
      by protonation of the N-bridges.

PMID- 28517016
TI  - Graphene as an electrode for solution-processed electron-transporting organic
      transistors.
AB  - Organic field-effect transistors (OFETs) are fundamental building blocks for
      plastic electronics such as organic photovoltaics or bendable displays with
      organic light emitting diodes, and radio-frequency identification (RFID) tags. A
      key part in the performance of OFET is the organic material constituting the
      channel. OFETs based on solution-processed polymers represent a new class of
      organic electronic devices. Recent developments in upscale solution-processed
      polymers have advanced towards high throughput, low-cost, and environmentally
      friendly materials for high-performance applications. Together with the
      integration of high performance materials, another enduring challenge in OFET
      development is the improvement and control of the injection of charge carriers.
      Graphene, a two-dimensional layer of covalently bonded carbon atoms, is steadily
      making progress into applications relying on van der Waals heterointerfaces with
      organic semiconductors. Here, we demonstrate the versatile operation of solution
      processed organic transistors both in lateral and vertical geometries by
      exploiting the weak-screening effect and work function modulation properties of
      graphene electrodes. Our results demonstrate a general strategy for overcoming
      traditional noble metal electrodes and to integrate graphene with solution
      processed Polyera ActiveInkTM N2200 polymer transistors for high-performance
      devices suitable for future plastic electronics.

PMID- 28517015
TI  - Genetic incorporation of 4-fluorohistidine into peptides enables selective
      affinity purification.
AB  - Due to the lowered pKa of 4-fluorohistidine relative to histidine, peptides and
      proteins containing this amino acid are potentially endowed with novel
      properties. We report here the optimized synthesis of 4-fluorohistidine and show
      that it can efficiently replace histidine in in vitro translation reactions.
      Moreover, peptides containing 6*-fluorohistidine tags are able to be selectively
      captured and eluted from nickel resin in the presence of his-tagged protein
      mixtures.

PMID- 28517020
TI  - Au-Cu core-shell nanocube-catalyzed click reactions for efficient synthesis of
      diverse triazoles.
AB  - Au-Cu core-shell nanocubes and octahedra synthesized in aqueous solution were
      employed to catalyze a 1,3-dipolar cycloaddition reaction between phenylacetylene
      and benzyl azide in water at 50  degrees C for 3 h. Interestingly, the nanocubes
      were far more efficient in catalyzing this reaction, giving 91% yield of a
      regioselective 1,4-triazole product, while octahedra only recorded 46% yield. The
      Au-Cu nanocubes were subsequently employed to catalyze the click reaction between
      benzyl azide and a broad range of aromatic and aliphatic alkynes. The product
      yields ranged from 78 to 99%. Clearly the Au-Cu cubes exposing {100} surfaces are
      an excellent and green catalyst for click reactions.

PMID- 28517021
TI  - Low discriminating power of the modified Ottawa VTE risk score in a cohort of
      patients with cancer from the RIETE registry.
AB  - Treatment of patients with cancer-associated venous thromboembolism (VTE) remains
      a major challenge. The modified Ottawa score is a clinical prediction rule
      evaluating the risk of VTE recurrences during the first six months of
      anticoagulant treatment in patients with cancer-related VTE. We aimed to validate
      the Ottawa score using data from the RIETE registry. A total of 11,123 cancer
      patients with VTE were included in the analysis. According to modified Ottawa
      score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41
      %) at intermediate risk, and 4,255 (38 %) at high risk. Overall, 477 episodes of
      VTE recurrences were recorded during the course of anticoagulant therapy, with an
      incidence rate for low, intermediate, and high risk groups of 6.88 % (95 % CI
      5.31-8.77), 11.8 % (95 % CI 10.1-13.6), and 21.3 % (95 % CI 18.8-24.1) patient
      years, respectively. Overall mortality had an incidence rate of 21.1 % (95 % CI
      18.2-24.3), 79.4 % (95 % CI: 74.9-84.1), and 134.7 % (95 % CI: 128.3-141.4)
      patient-years, respectively. The accuracy and discriminating power of the
      modified Ottawa score for VTE recurrence was modest, with low sensitivity,
      specificity and positive predictive value, and a C-statistics of 0.58 (95 % CI:
      0.56-0.61). In our analysis, the modified Ottawa score did not accurately predict
      VTE recurrence among patients with cancer-associated thrombosis, thus hindering
      its use in clinical practice. It is time to define a new score including other
      clinical predictors.

PMID- 28517022
TI  - Impact and management of left ventricular function on the prognosis of Takotsubo
      syndrome.
AB  - BACKGROUND: Early research has proposed that patients with Takotsubo syndrome
      (TTS) could have a higher mortality rate than the general population. Our study
      was conducted to determine the short- and long-term outcome of TTS patients
      associated with a significantly compromised left ventricular function on hospital
      admission. MATERIALS AND METHODS: Our institutional database constituted a
      collective of 112 patients diagnosed with TTS between 2003 and 2015. The patients
      were classified into two groups based on the left ventricular ejection fraction
      (LVEF), with those presenting with a LVEF > 35% on admission categorized into one
      group (n = 65, 58%) and those presenting with LVEF <= 35% (n=47, 42%) categorized
      into another group. The endpoint was the all-cause of mortality over a mean
      follow-up of 1529 +/- 1121 days. RESULTS: Preliminary results indicated that
      patients with an EF <= 35% had a significantly greater risk of developing life
      threatening arrhythmias, and were much more likely to suffer from cardiogenic
      shock. Patients often required varying forms of mechanical respiratory support.
      The in-hospital mortality, 30-day mortality, 1-year mortality and ongoing long
      term mortality was significantly higher in TTS patients with an EF <= 35%. In a
      multivariate Cox regression analysis, an EF <= 35% (HR 3.3, 95% CI: 1.2-9.2, P <
      0.05) was identified as a strong independent predictor of the primary endpoint.
      CONCLUSIONS: In-hospital events as well as short- and long-term mortality rates
      among TTS patients diagnosed with a significantly reduced LVEF on admission were
      significantly higher. There is an urgent need for randomized trials, which could
      help define uniform clinical management strategies for high risk TTS patients.

PMID- 28517023
TI  - Shifts in water availability mediate plant-pollinator interactions.
AB  - Altered precipitation patterns associated with anthropogenic climate change are
      expected to have many effects on plants and insect pollinators, but it is unknown
      if effects on pollination are mediated by changes in water availability. We
      tested the hypothesis that impacts of climate on plant-pollinator interactions
      operate through changes in water availability, and specifically that such effects
      occur through alteration of floral attractants. We manipulated water availability
      in two naturally occurring Mertensia ciliata (Boraginaceae) populations using
      water addition, water reduction and control plots and measured effects on
      vegetative and floral traits, pollinator visitation and seed set. While most
      floral trait values, including corolla size and nectar, increased linearly with
      increasing water availability, in this bumblebee-pollinated species, pollinator
      visitation peaked at intermediate water levels. Visitation also peaked at an
      intermediate corolla length, while its relationship to corolla width varied
      across sites. Seed set, however, increased linearly with water. These results
      demonstrate the potential for changes in water availability to impact plant
      pollinator interactions through pollinator responses to differences in floral
      attractants, and that the effects of water on pollinator visitation can be
      nonlinear. Plant responses to changes in resource availability may be an
      important mechanism by which climate change will affect species interactions.

PMID- 28517024
TI  - Treatment of severe alcoholic hepatitis: past, present and future.
AB  - Alcoholic hepatitis (AH) manifests as a clinical syndrome characterized by recent
      jaundice and liver function deterioration in an actively drinking patient. The
      principal cause of AH is alcoholic steatohepatitis (ASH) defined histologically
      by the coexistence of steatosis, hepatocyte ballooning and satellitosis. While
      nonsevere AH usually responds to alcohol abstinence, severe AH, identified by
      Maddrey scoring >= 32, has a bad prognosis and is traditionally treated by a 28
      day course of prednisone therapy. A recent trial, which showed no improvement of
      long-term survival but significant reduced mortality after 28 days of corticoid
      therapy compared to placebo, opens a debate on its efficacy. N-acetyl-cysteine
      supplementation combined with steroid therapy is also able to reduce the 28-day
      mortality compared to steroid alone. While guidelines recommend high-calorie
      intake and protein supplementation in decompensated liver diseases, intensive
      enteral nutrition together with corticoid treatment does not reduce mortality
      compared to corticoid alone in a recent study with ASH patients. Stimulation of
      liver regeneration through interleukin-22, granulocyte colony-stimulating factor
      or farnesoid X receptor agonists, inhibition of apoptosis, early liver
      transplantation and modulation of gut microbiota through antibiotic or faecal
      transplantation approaches constitute new therapeutic perspectives that are
      investigated in current clinical trials. Inhibition of oxidative stress,
      modulation of gut fungal populations and stimulation of progenitor cell
      proliferation and pro-regenerative inflammatory pathways constitute prospects for
      future human trials. For long-term survival, strategies for persistent alcohol
      abstinence remain the key of success, opening another large research field.

PMID- 28517026
TI  - Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary
      arterial pressure measured by Doppler echocardiography: Analysis in an unselected
      patient population.
AB  - Pulmonary arterial pressure is an important index in cardiovascular disorders,
      especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is
      widely used as a noninvasive method to assess pulmonary arterial pressure.
      However, recent studies have found several hemodynamic factors that affect its
      accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the
      effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our
      study is aimed to determine whether the severity of TR will affect the accuracy
      of sPAP measured by DE in an unselected patient population. We retrospectively
      studied 177 patients who underwent DE and right heart catheterization (RHC)
      examinations. Patients were categorized into 3 groups according to the severity
      of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and
      RHC was calculated and compared in each group. Determinants of discordant results
      between two methods were also evaluated. Age, gender, interval between DE and
      RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in
      sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in
      group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05).
      The difference in sPAP between DE and RHC was affected independently by severe TR
      and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP
      measured by DE. Modification of echocardiographic sPAP measurements by taking
      into consideration of these factors may lead to reduced systemic errors.

PMID- 28517027
TI  - Lung function parameters in omalizumab responder patients: An interesting tool?
AB  - BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with
      severe allergic asthma. The evolution of lung function parameters over time and
      the difference between omalizumab responder and nonresponder patients remain
      inconclusive. The objective of this real-life study was to compare the changes in
      forced expiratory volume in 1 second (FEV1) of omalizumab responders and
      nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10
      secondary and tertiary institutions. Lung function parameters (forced vital
      capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total
      lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab
      response was assessed at the 6-month visit. In the omalizumab responder patients,
      lung function parameters were also obtained at 12, 18, and 24 months. RESULTS:
      Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a
      decrease was observed in nonresponders (+0.2+/-0.4 L and -0.1+/-0.4 L,
      respectively, P<.01). After an improvement at 6 months, pre- and
      postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC
      remained unchanged over time, but the proportion of patients with an FEV1/FVC
      ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%,
      respectively, P<.05). Mean RV values decreased at 6 months but increased at 12
      months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio
      decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After
      omalizumab initiation, FEV1 improved at 6 months in responder patients and then
      remained stable for 2 years. RV and RV/TLC improved at 6 months.

PMID- 28517028
TI  - AIC identifies optimal representation of longitudinal dietary variables.
AB  - OBJECTIVES: The Akaike Information Criterion (AIC) is a well-known tool for
      variable selection in multivariable modeling as well as a tool to help identify
      the optimal representation of explanatory variables. However, it has been
      discussed infrequently in the dental literature. The purpose of this paper is to
      demonstrate the use of AIC in determining the optimal representation of dietary
      variables in a longitudinal dental study. METHODS: The Iowa Fluoride Study
      enrolled children at birth and dental examinations were conducted at ages 5, 9,
      13, and 17. Decayed or filled surfaces (DFS) trend clusters were created based on
      age 13 DFS counts and age 13-17 DFS increments. Dietary intake data (water, milk,
      100 percent-juice, and sugar sweetened beverages) were collected semiannually
      using a food frequency questionnaire. Multinomial logistic regression models were
      fit to predict DFS cluster membership (n=344). Multiple approaches could be used
      to represent the dietary data including averaging across all collected surveys or
      over different shorter time periods to capture age-specific trends or using the
      individual time points of dietary data. RESULTS: AIC helped identify the optimal
      representation. Averaging data for all four dietary variables for the whole
      period from age 9.0 to 17.0 provided a better representation in the multivariable
      full model (AIC=745.0) compared to other methods assessed in full models
      (AICs=750.6 for age 9 and 9-13 increment dietary measurements and AIC=762.3 for
      age 9, 13, and 17 individual measurements). The results illustrate that AIC can
      help researchers identify the optimal way to summarize information for inclusion
      in a statistical model. CONCLUSIONS: The method presented here can be used by
      researchers performing statistical modeling in dental research. This method
      provides an alternative approach for assessing the propriety of variable
      representation to significance-based procedures, which could potentially lead to
      improved research in the dental community.

PMID- 28517030
TI  - Gerbode defect and multivalvular dysfunction: Complex complications in adult
      congenital heart disease.
AB  - We report a clinical case of a 40-year-old male with surgically corrected
      congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral
      annuloplasty, and aortic valve and root surgery. The patient was admitted with
      acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic
      and severely incompetent aortic valve, a partial tear of the mitral valve cleft
      repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial
      shunt confirmed a direct Gerbode defect. The authors aim to discuss the
      diagnostic challenge of adult CHD, namely the key role of TEE on septal defects
      and valve regurgitations description.

PMID- 28517029
TI  - Carbon-driven enrichment of the crucial nitrate-reducing bacteria in limed peat
      soil microcosms.
AB  - : Bacteria of Dechloromonas were recognized as potential functional important
      denitrifiers in a long-term shell sand-amended peat soil. Different microcosms in
      a solid matrix and slurry systems with the addition of carbon and nitrogen
      sources, for example, clover leaves, glutamate and nitrate, were established. The
      bacterial community structures were analysed by pyrosequencing of the 16S rRNA
      gene to select the conditions for enriching bacteria of Dechloromonas. The
      results showed that a relatively even bacterial community in the initial soil
      shifted to communities dominated by a few types of nitrate-reducing bacteria
      after the incubation, which strongly responded to the carbon substrates addition
      and consumption. The bacteria of several genera including Dechloromonas,
      Pseudomonas, Clostridium, Aeromonas and Ferribacterium were significantly
      enriched after a certain period of time. The bacteria of Dechloromonas became one
      of the most predominant bacteria in the incubated community. Especially when
      added the mixed carbon substrates into the solid soil matrix, as high as 34% of
      abundance was detected. This study proved that the functional important bacteria
      from the genus of Dechloromonas could be enriched to an extremely high abundance
      by using proper culture condition which will benefit to the isolation or direct
      metagenomics study for Dechloromonas. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      study of key players in a microbial community is always of important. In this
      study, the functional important denitrifiers in a shell sand-amended peat soil
      were investigated. Using different carbon sources in the incubation, we found the
      bacteria from the genus of Dechloromonas were enriched to an abundance of higher
      than 34% with several other denitrifiers together. This work provides us helpful
      insights not only for knowing the diversity of denitrifiers in the studied peat
      soil, but also for understanding their response to the carbon sources and the
      culture conditions.

PMID- 28517031
TI  - An isolated ulcerated forehead lesion in a 70-year-old man.

PMID- 28517032
TI  - Novel psychoactive substance consumption is more represented in bipolar disorder
      than in psychotic disorders: A multicenter-observational study.
AB  - OBJECTIVE: Comorbidities between psychiatric diseases and use of traditional
      substances of abuse are common. Nevertheless, there are few data regarding the
      use of novel psychoactive substances (NPS) among psychiatric patients. Aim of
      this multicentre survey is to investigate the consumption of a number of
      psychoactive substances in a young psychiatric sample. METHODS: Between December
      2013 and September 2015, a questionnaire was administered in 10 Italian
      psychiatric care facilities to a sample of 671 patients, aged 18-26 (mean age
      22.24; SD 2.87). RESULTS: About 8.2% of the sample declared to have used NPS at
      least once, and 2.2% had consumed NPS in the previous 3 months. The three
      psychiatric diagnoses most frequently associated with NPS use were bipolar
      disorder (23.1%), personality disorders (11.8%), and schizophrenia and related
      disorders (11.6%). In univariate regression analysis, bipolar disorder was
      positively associated with NPS consumption, an association that did not reach
      statistical significance in the multivariate analysis. CONCLUSIONS: The use of
      NPS in a young psychiatric population appears to be frequent, and probably still
      underestimated. Bipolar disorder shows an association with NPS use. Careful and
      constant monitoring and an accurate evaluation of possible clinical effects
      related to NPS use are necessary.

PMID- 28517033
TI  - High-throughput sequencing of transposable element insertions suggests adaptive
      evolution of the invasive Asian tiger mosquito towards temperate environments.
AB  - Invasive species represent unique opportunities to evaluate the role of local
      adaptation during colonization of new environments. Among these species, the
      Asian tiger mosquito, Aedes albopictus, is a threatening vector of several human
      viral diseases, including dengue and chikungunya, and raises concerns about the
      Zika fever. Its broad presence in both temperate and tropical environments has
      been considered the reflection of great "ecological plasticity." However, no
      study has been conducted to assess the role of adaptive evolution in the
      ecological success of Ae. albopictus at the molecular level. In the present
      study, we performed a genomic scan to search for potential signatures of
      selection leading to local adaptation in one-hundred-forty field-collected
      mosquitoes from native populations of Vietnam and temperate invasive populations
      of Europe. High-throughput genotyping of transposable element insertions led to
      the discovery of more than 120,000 polymorphic loci, which, in their great
      majority, revealed a virtual absence of structure between the biogeographic
      areas. Nevertheless, 92 outlier loci showed a high level of differentiation
      between temperate and tropical populations. The majority of these loci segregate
      at high insertion frequencies among European populations, indicating that this
      pattern could have been caused by recent adaptive evolution events in temperate
      areas. An analysis of the overlapping and neighbouring genes highlighted several
      candidates, including diapause, lipid and juvenile hormone pathways.

PMID- 28517035
TI  - A Biomass-Derived Non-Noble Cobalt Catalyst for Selective Hydrodehalogenation of
      Alkyl and (Hetero)Aryl Halides.
AB  - Hydrodehalogenation is a straightforward approach for detoxifications of harmful
      anthropogenic organohalide-based pollutants, as well as removal of halide
      protecting groups used in multistep syntheses. A novel sustainable catalytic
      material was prepared from biowaste (chitosan) in combination with an earth
      abundant cobalt salt. The heterogeneous catalyst was fully characterized by
      transmission electron microscope, X-ray diffraction, and X-ray photoelectron
      spectroscopy measurements, and successfully applied to hydrodehalogenation of
      alkyl and (hetero)aryl halides with broad scope (>40 examples) and excellent
      chemoselectivity using molecular hydrogen as a reductant. The general usefulness
      of this method is demonstrated by successful detoxification of non-degradable
      pesticides and fire retardants. Moreover, the potential of the catalyst as a
      deprotection tool is demonstrated in a multistep synthesis of (+/-)-peronatin B
      (alkaloid).

PMID- 28517036
TI  - Prevalence of muscle weakness based on different diagnostic criteria in community
      dwelling older adults: A comparison of grip strength dynamometers.
AB  - AIM: The present study compared the performance of the Jamar and Smedley
      dynamometers for the measurement of grip strength, and the two dynamometers were
      used to determine the prevalence rate of weakness in a large, community-dwelling,
      older adult population, based on different diagnostic criteria. METHODS: A total
      of 467 community-dwelling older adults aged 69-89 years were recruited into the
      study. Grip strength was measured with two dynamometers; the Jamar hydraulic hand
      dynamometer was used as the reference device. To assess agreement between grip
      strength measurements by the two dynamometers, linear regression and Bland-Altman
      analyses were carried out. RESULTS: In a comparison of the dynamometers, high
      coefficients of determination (R2 ) were obtained for grip strength (R2 = 0.80,
      standard error of the estimate 2.68 kg in male participants, and R2 = 0.75,
      standard error of the estimate = 1.95 kg in female participants). There was
      systematic bias with underestimation of grip strength (bias 3.09 kg, 95%
      confidence interval 2.77 to 3.41 for men; bias 2.60 kg, 95% confidence interval
      2.31 to 2.89 for women) by the Smedley dynamometer. In both sexes, no
      proportional bias was noted between the two dynamometers for measurement of grip
      strength (r = 0.030, P = 0.611 for male participants; r = -0.033, P = 0.653 for
      female participants). The prevalence of weakness ranged from 1.8 to 19.9% in male
      participants, and 0.5 to 27.4% in female participants. CONCLUSIONS: The present
      study shows that despite the excellent correlation between the two dynamometers,
      there is a statistically significant difference in grip strength measurements.
      The Smedley dynamometer showed a higher prevalence of weakness than did the Jamar
      dynamometer. Geriatr Gerontol Int 2017; 17: 2089-2095.

PMID- 28517034
TI  - Comparative musculoskeletal anatomy of chameleon limbs, with implications for the
      evolution of arboreal locomotion in lizards and for teratology.
AB  - Chameleon species have recently been adopted as models for evo-devo and
      macroevolutionary processes. However, most anatomical and developmental studies
      of chameleons focus on the skeleton, and information about their soft tissues is
      scarce. Here, we provide a detailed morphological description based on contrast
      enhanced micro-CT scans and dissections of the adult phenotype of all the
      forelimb and hindlimb muscles of the Veiled Chameleon (Chamaeleo calyptratus) and
      compare these muscles with those of other chameleons and lizards. We found the
      appendicular muscle anatomy of chameleons to be surprisingly conservative
      considering the remarkable structural and functional modifications of the limb
      skeleton, particularly the distal limb regions. For instance, the zygodactyl
      autopodia of chameleons are unique among tetrapods, and the carpals and tarsals
      are highly modified in shape and number. However, most of the muscles usually
      present in the manus and pes of other lizards are present in the same
      configuration in chameleons. The most obvious muscular features related to the
      peculiar opposable autopodia of chameleons are: (1) presence of broad, V-shaped
      plantar and palmar aponeuroses, and absence of intermetacarpales and
      intermetatarsales, between the digits separated by the cleft in each autopod; (2)
      oblique orientation of the superficial short flexors originating from these
      aponeuroses, which may allow these muscles to act as powerful adductors of the
      "super-digits"; and (3) well-developed abductor digiti minimi muscles and
      abductor pollicis/hallucis brevis muscles, which may act as powerful abductors of
      the "super-digits."

PMID- 28517038
TI  - Do trainees feel that they belong to a team?
AB  - BACKGROUND: Postgraduate medical education has undergone significant
      reorganisation in recent years, with changes to the traditional apprenticeship
      model and an increasing reliance on shift working. The importance of teamwork in
      clinical care is well established; however, there is little literature on the
      extent to which trainees actually feel part of a team in the context of current
      working patterns. METHOD: This is a qualitative study using semi-structured
      interviews of medical and surgical trainees. Data were analysed thematically
      using an inductive qualitative approach. RESULTS: Fifteen trainees who had worked
      in a range of hospitals across the UK participated. Emerging themes fell into
      several categories: what constitutes the team; the effect of shift patterns on
      the team; the role of the team in education, support and well-being; and
      influences on team rapport. Whilst in general interviewees felt part of a team,
      this was not true for all posts. The nature of the team was also highly variable,
      and had evolved from the traditional 'Firm' structure to a more nebulous concept.
      Shift-working patterns could result in the fragmentation of the team, which had
      implications for patient care as well as for training. DISCUSSION: The team
      played an important role in both education and well-being for trainees, and
      several factors were identified that could engender a more supportive team. With
      an ageing population and with increasing demands on limited resources, the
      requirement for shift work is likely to increase, and there is a fundamental need
      to maintain support for the next generation of doctors. There is little
      literature on the extent to which trainees actually feel part of a team.

PMID- 28517037
TI  - Serum phosphate is related to adiposity in healthy adults.
AB  - BACKGROUND: Inorganic phosphate is a crucial component of cellular energy
      metabolism. We have identified an inverse relationship between serum phosphate
      concentration and fat mass in a cohort of healthy men. This study reports those
      data and determines whether this association is present in two female
      populations. METHODS: Cross-sectional data from three independent cohorts,
      consisting of healthy adult males (Male Cohort, n = 323) and healthy
      postmenopausal women (Female Cohort 1, n = 185; and Female Cohort 2, n = 1471),
      are reported. Associations between serum phosphate and weight, body mass index
      (BMI), fat mass and bone mineral density (BMD) were assessed. In a fourth cohort
      of postmenopausal women (FGF23 Cohort, n = 20), associations between fibroblast
      growth factor 23 (FGF23), weight and BMI were assessed. RESULTS: Serum phosphate
      correlated inversely with weight, BMI and fat mass across all three cohorts (r = 
      0.13 to -0.31, P < 0.0001-0.02). Associations were diminished after adjustment
      for PTH, but remained significant. In the FGF23 Cohort, FGF23 was positively
      correlated with weight (r = 0.60, P = 0.007) and BMI (r = 0.49, P = 0.03).
      Phosphate was inversely associated with BMD in Female Cohorts 1 and 2 (r = -0.08
      to -0.29, P < 0.0001-0.02). This relationship was attenuated, but remained
      significant at most sites, following adjustment for age, fat mass, renal function
      and 25-hydroxyvitamin D. CONCLUSIONS: Serum phosphate is inversely associated
      with measures of adiposity in both women and men, largely independently of PTH.
      FGF23 might mediate these associations. This relationship may be an unrecognized
      confounder in some of the correlates of serum phosphate already described.

PMID- 28517039
TI  - Genetics of mycorrhizal symbiosis in winter wheat (Triticum aestivum).
AB  - Bread wheat (Triticum aestivum) is a major staple food and therefore of prime
      importance for feeding the Earth's growing population. Mycorrhiza is known to
      improve plant growth, but although extensive knowledge concerning the interaction
      between mycorrhizal fungi and plants is available, genotypic differences
      concerning the ability of wheat to form mycorrhizal symbiosis and quantitative
      trait loci (QTLs) involved in mycorrhization are largely unknown. Therefore, a
      diverse set of 94 bread wheat genotypes was evaluated with regard to root
      colonization by arbuscular mycorrhizal fungi. In order to identify genomic
      regions involved in mycorrhization, these genotypes were analyzed using the wheat
      90k iSelect chip, resulting in 17 823 polymorphic mapped markers, which were used
      in a genome-wide association study. Significant genotypic differences (P <
      0.0001) were detected in the ability to form symbiosis and 30 significant markers
      associated with root colonization, representing six QTL regions, were detected on
      chromosomes 3A, 4A and 7A, and candidate genes located in these QTL regions were
      proposed. The results reported here provide key insights into the genetics of
      root colonization by mycorrhizal fungi in wheat.

PMID- 28517040
TI  - Thoughts of being an imposter, in medical students.

PMID- 28517041
TI  - Modifying illness beliefs in recent onset psychosis carers: Evaluating the impact
      of a cognitively focused brief group intervention in a routine service.
AB  - AIMS: At first-episode psychosis (FEP), many patients will be routed within
      familial networks and supported by informal carers who are predominately close
      family members such as parents. Carer burden, distress and poorer coping styles
      are associated with different illness beliefs. The current study sought to
      examine the impact and acceptability of a 3 session, cognitively informed, group
      intervention targeting illness beliefs previously linked to distress and poorer
      caregiving experiences in FEP carers. METHODS: Carers attending a routine FEP
      service were invited to attend the group intervention and completed a measure of
      illness beliefs at baseline and post intervention. RESULTS: Data on 68 carers
      with complete datasets are presented. Carers were predominately females (64.2%).
      Group attendance was linked to positive improvements in carer baseline beliefs
      about the negative consequences of the illness for the patient and themselves,
      attributions of blame about the illness to the patient and themselves and their
      overall understanding about the illness. Significant improvements in their
      understanding of the illness timeline and course, and confidence in dealing with
      difficulties were also identified. CONCLUSIONS: A cognitively informed group
      approach to targeting the less adaptive illness beliefs reported by FEP carers
      may offer an effective and acceptable pathway to facilitate their understanding
      of the illness and adjustment. Further studies using controlled designs are
      required.

PMID- 28517042
TI  - The Impact of the ACA Medicaid Expansions on Health Insurance Coverage through
      2015 and Coverage Disparities by Age, Race/Ethnicity, and Gender.
AB  - OBJECTIVE: Examine the ACA Medicaid expansion effects on Medicaid take-up and
      private coverage through 2015 and coverage disparities by age, race/ethnicity,
      and gender. DATA SOURCES: 2011-2015 American Community Survey for 3,137,989 low
      educated adults aged 19-64 years. STUDY DESIGN: Difference-in-differences
      regressions accounting for national coverage trends and state fixed effects.
      PRINCIPAL FINDINGS: Expansion effects doubled in 2015 among low-educated adults,
      with a nearly 8 percentage-point increase in Medicaid take-up and 6 percentage
      point decline in uninsured rate. Significant coverage gains were observed across
      virtually all examined groups by age, gender, and race/ethnicity. Take-up and
      insurance declines were strongest among younger adults and were generally close
      by gender and race/ethnicity. Despite the increased take-up however, coverage
      disparities remained sizeable, especially for young adults and Hispanics who had
      declining but still high uninsured rates in 2015. There was some evidence of
      private coverage crowd-out in certain subgroups, particularly among young adults
      aged 19-26 years and women, including in both individually purchased and employer
      sponsored coverage. CONCLUSIONS: The ACA Medicaid expansions have continued to
      increase coverage in 2015 across the entire population of low-educated adults and
      have reduced age disparities in coverage. However, there is still a need for
      interventions that target eligible young and Hispanic adults.

PMID- 28517044
TI  - Intercentrum versus pleurocentrum growth in early tetrapods: A paleohistological
      approach.
AB  - A variety of vertebral centrum morphologies have evolved within early tetrapods
      which range from multipartite centra consisting of intercentra and pleurocentra
      in stem-tetrapods, temnospondyls, seymouriamorphs, and anthracosaurs up to
      monospondylous centra in lepospondyls. With the present study, we aim to
      determine the formation of both intercentrum and pleurocentrum and asked whether
      these can be homologized based on their bone histology. Both intercentra and
      pleurocentra ossified endochondrally and periosteal bone was subsequently
      deposited on the outer surface of the centra. Our observations indicate low
      histological variation between intercentrum and pleurocentrum in microstructural
      organization and growth which inhibits the determination of homologies. However,
      intercentrum and pleurocentrum development differs during ontogeny. As previously
      assumed, the intercentrum arises from ventrally located and initially paired
      ossification centers that fuse ventromedially to form the typical, crescentic,
      rhachitomous intercentrum. In contrast, presacral pleurocentra may be ancestrally
      represented by four ossification centers: a ventral and a dorsal pair.
      Subsequently, two divergent developmental patterns are observed: In stem
      tetrapods and temnospondyls, the pleurocentrum evolves from the two dorsally
      located ossification centers which may occasionally fuse to form a dorsal
      crescent. In some dvinosaurian temnospondyls, the pleurocentrum may even ossify
      to full rings. In comparison, the pleurocentrum of stem-amniotes (anthracosaurs,
      chroniosuchids, seymouriamorphs, and lepospondyls) arises from the two ventrally
      located ossification centers whereby the ossification pattern is almost identical
      to that of temnospondyls but mirror-inverted. Thus, the ring-shaped pleurocentrum
      of Discosauriscus ossifies from ventral to dorsal. We also propose that the
      ossified portions of the intercentrum and pleurocentrum continued as
      cartilaginous rings or discs that surrounded the notochord in the living animals.

PMID- 28517043
TI  - Sperm chromatin quality and DNA integrity in partial versus total
      globozoospermia.
AB  - Globozoospermia is a severe form of teratozoospermia with low incidence in
      infertile patients, considered as one of the important causes of male
      infertility. The objective was to investigate the chromatin/DNA integrity as well
      as apoptosis in ejaculated spermatozoa of cases with partial or total
      globozoospermia. Fifty-seven semen samples were divided into three groups of
      partial globozoospermia (n = 17), total globozoospermia (n = 10) and
      normozoospermia (control; n = 30). Sperm chromatin condensation, DNA integrity
      and apoptosis were assessed using cytochemical assays. The results showed
      significant differences in sperm parameters of count and motility between two
      case groups versus controls. The percentages of spermatozoa with abnormal
      chromatin packaging and protamine deficiency were significantly higher in total
      and partial globozoospermic men compared to normozoospermic samples. Also, the
      rates of TUNEL-positive spermatozoa were significantly increased in both
      globozoospermic cases with respect to the control (18.3 +/- 10.1 and 12.3 +/- 9.2
      versus 5.9 +/- 3 respectively). However, no significant differences were noticed
      between two subgroups of patients with regard to sperm DNA denaturation, DNA
      fragmentation and apoptosis. Abnormal chromatin packaging, DNA damage and
      apoptosis were significantly higher in cases than controls. The sperm
      chromatin/DNA anomalies may be considered as one of the main aetiology of ART
      failure in globozoospermic patients.

PMID- 28517046
TI  - Three-dimensional proximal flow convergence automatic calculation for determining
      mitral valve area in rheumatic mitral stenosis.
AB  - PURPOSE: Management of patients with mitral stenosis (MS) depends heavily on the
      accurate quantification of mitral valve area (MVA) using echocardiography. All
      currently used two-dimensional (2D) methods have limitations. Estimation of MVA
      using the proximal isovelocity surface area (PISA) method with real time three
      dimensional (3D) echocardiography may circumvent those limitations. We aimed to
      evaluate the accuracy of 3D direct measurement of PISA in the estimation of MVA.
      METHODS: Twenty-seven consecutive patients (median age of 63 years; 77.8%
      females) with rheumatic MS were prospectively studied. Transthoracic and
      transesophageal echocardiography with 2D and 3D acquisitions were performed on
      the same day. The reference method for MVA quantification was valve planimetry
      after 3D-volume multiplanar reconstruction. A semi-automated software was used to
      calculate the 3D flow convergence volume. RESULTS: Compared to MVA estimation
      using 3D planimetry, 3D PISA showed the best correlation (rho=0.78, P<.0001),
      followed by pressure half-time (PHT: rho=0.66, P<.001), continuity equation (CE:
      rho=0.61, P=.003), and 2D PISA (rho=0.26, P=.203). Bland-Altman analysis revealed
      a good agreement for MVA estimation with 3D PISA (mean difference -0.03 cm2 ;
      limits of agreement (LOA) -0.40-0.35), in contrast to wider LOA for 2D methods:
      CE (mean difference 0.02 cm2 , LOA -0.56-0.60); PHT (mean difference 0.31 cm2 ,
      LOA -0.32-0.95); 2D PISA (mean difference -0.03 cm2 , LOA -0.92-0.86).
      CONCLUSIONS: MVA estimation using 3D PISA was feasible and more accurate than 2D
      methods. Its introduction in daily clinical practice seems possible and may
      overcome technical limitations of 2D methods.

PMID- 28517047
TI  - SU-E-T-612: Hybrid-Input-Output Algorithm for IMRT Optimization with Dose-Volume
      Histogram Constraints.
AB  - PURPOSE: Dose-volume histogram (DVH) is a clinically relevant criterion to
      evaluate a treatment plan quality. It is hence desirable to incorporate DVH
      constraints in treatment planning process for intensity modulated radiation
      therapy (IMRT). Yet, these constraints usually lead to difficulties due to their
      non-convex nature. The purpose of this project is to solve the IMRT optimization
      problem with DVH constraints using a hybrid-input-output (HIO) method. METHODS:
      The IMRT optimization problem finds a dose distribution z under two constraints,
      where the elements of the vector z are the dose value at each spatial coordinate.
      First, there exist a corresponding fluence map x such that Dx=z and x>0, where D
      is the dose deposition matrix. Second, the dose distribution z should satisfy the
      DVH constraints. These two constraints define two sets of the dose distributions,
      denoted by A and B, and the solution to the IMRT problem lies in the intersection
      of these two sets. Our method finds the solution via the HIO algorithm that
      iteratively updates the solution according to its projections onto the two sets
      until convergence. The projection to A is handled by solving a least square
      problem and the projection to B is achieved by gradually adjusting voxel doses
      that validate the DVH criteria to meet the constraints. RESULTS: We have tested
      our algorithm using 7-field IMRT plans for 4 prostate cancer cases. Clinically
      relevant DVH constraints are considered for PTV, rectum, and bladder. In all the
      cases, the algorithm is able to find the solutions that satisfy all the DVH
      constraints. CONCLUSIONS: We have developed an algorithm to solve the IMRT
      optimization problem with DVH constraints using the HIO approach. Tests conducted
      in prostate cancer cases have demonstrated the effectiveness of our algorithm.

PMID- 28517045
TI  - SET DOMAIN GROUP701 encodes a H3K4-methytransferase and regulates multiple key
      processes of rice plant development.
AB  - Chromatin-based epigenetic information plays an important role in developmental
      gene regulation, in response to environment, and in natural variation of gene
      expression levels. Histone H3 lysine 4 di/trimethylation (H3K4me2/3) is abundant
      in euchromatin and is generally associated with transcriptional activation.
      Strikingly, however, enzymes catalyzing H3K4me2/3 remain poorly characterized in
      crops so far. Here, we investigated the function of the rice SET DOMAIN GROUP 701
      (SDG701) gene by molecular and biochemical characterization of the gene product,
      and by studying effects of its loss or gain of function on plant growth and
      development. We demonstrated that SDG701 encodes a methytransferase specifically
      catalyzing H3K4 methylation. Overexpression and knockdown experiments showed that
      SDG701 is crucial for proper sporophytic plant development as well as for
      gametophytic transmission that directly impacts rice grain production. In-depth
      analysis of plant flowering time revealed that SDG701 promotes rice flowering
      under either long-day or short-day photoperiods. Consistently, the SDG701 protein
      was found to bind chromatin to promote H3K4me3 and to enhance expression of the
      rice Hd3a and RFT1 florigens. Collectively, our results establish SDG701 as a
      major rice H3K4-specific methyltransferase and provide important insights into
      function of H3K4me3 deposition in transcription activation of florigens in
      promoting plant flowering.

PMID- 28517049
TI  - SU-E-T-616: Efficacy of Biological Dose Painting for Head and Neck Cancer.
AB  - PURPOSE: Study the feasibility and planning robustness of a novel biological dose
      painting approach prescribing biological effect instead of dose. METHODS:
      Prescribed'effect maps' were generated using models relating FMISO-PET tracer
      uptake to hypoxia reduction factors (HRF). HRFs decrease the LQ-model radio
      response parameters a and beta and therefore the delivered biological effect. The
      model is driven by four parameters (m, K, p50, Imax), whose values have been
      determined through a comprehensive literature search. A planning study on ten
      previously treated patients with oropharyngeal cancer was conducted. Dose-painted
      plans were generated with the KonRad inverse planning system (DKFZ, Heidelberg).
      Simulated FMISO-PET images were generated by defining clinically relevant hypoxic
      sub-volumes within the GTV. Tracer uptake values were derived from various PET
      imaging studies for head and neck cancer. Each treatment plan was developed in
      four steps: 1) Simulate hypoxia tracer distribution in GTV. 2) Prescribe
      biological effect. 3) Optimize dose-painted plan under the same normal tissue
      constraints of the nominal clinical plan. 4) Conduct robustness analysis by
      evaluation of the dose-painted plan for 27 parameters combinations of K, m, p50
      (mean +/- 1SD). RESULTS: The predicted biological effect of clinical plans under
      normoxic conditions overestimates the delivered effect due to decreased radio
      sensitivity in hypoxic tumours. Biological dose painting compensates for hypoxia
      by delivering a higher dose to hypoxic sub-volumes while still maintaining all
      critical structure dose limits. Model parameter uncertainties clearly affect
      robustness. The high uncertainty on p50 (pO2 for which tracer concentration is
      half of maximum uptake) was found to cause the largest variations in the
      delivered biological effect. CONCLUSIONS: Clinically acceptable dose-painted
      plans can be generated without sacrificing the normal tissue constraints.
      Planning robustness suffers from the high uncertainty on the p50 value. Improved
      methods to determine the model parameters would be desirable. Financial support
      provided by Ryerson University, Toronto, Ontario, Canada.

PMID- 28517048
TI  - SU-E-T-571: Prostate IMRT QA: Prediction of the Range of Rectal NTCP Using a 2D
      Field Approach Based on Variations of the Rectal Wall Motion and Thickness.
AB  - PURPOSE: The aims of this study is to (1) introduce a 2D field of possible rectal
      normal tissue complication probability (NTCP) in prostate intensity modulated
      radiotherapy (IMRT) plan, so that based on a given prescribed dose the rectal
      NTCP is merely a function of the rectal wall thickness and rectal motion; and (2)
      separate the 2D field of rectal NTCP into area of low risk and area of high risk
      for rectal toxicity < Grade II, based on the threshold rectal NTCP. METHODS: The
      2D field of NTCP model was developed using ten randomly selected prostate IMRT
      plans. The clinical rectal geometry was initially represented by the cylindrical
      contour in the treatment planning system. Different combinations of rectal
      motions, rectal wall thicknesses, planning target volume margins and prescribed
      doses were used to determine the NTCP in prostate IMRT plans. RESULTS: It was
      found that the functions bordering the 2D field for the given AP, LR and SI
      direction can be described as exponential, quadratic and linear equations,
      respectively. A ratio of the area of 2D field containing data of the low risk
      NTCP to the entire area of the field was introduced and calculated. Although our
      method is based on the Kutcher's dose response model and published tissue
      parameters, other mathematical models can be used in our approach. CONCLUSIONS:
      The 2D field of rectal NTCP is useful to estimate the rectal NTCP range in the
      prostate pre-treatment and treatment QA. Our method can determine the patient's
      threshold immobilization for a given rectal wall thickness so that prescribed
      dose can be delivered to the prostate to avoid rectal complication. Our method is
      also applicable to multi-phase prostate IMRT, and can be adapted to any treatment
      planning systems.

PMID- 28517050
TI  - SU-E-T-582: Assessment of Improved Critical Structure Sparing Using Biologically-
      Based Optimization for Volumetric Modulated Arc Therapy of Head and Neck Cancer.
AB  - PURPOSE: To investigate the critical structure sparing achievable by biological
      optimization for modulated volumetric arc (VMAT) of head and neck (H&N) cancer.
      METHODS: Ten H&N VMAT patients who were originally planned and treated with
      simultaneous integrated boost technique using dose-volume based optimization,
      were selected. For each patient, a new VMAT plan was generated using the
      generalized equivalent uniform dose (gEUD)-based biological optimization
      available in Pinnacle3 Smart Arc. While the objectives for targets were defined
      in terms of minimum and maximum EUDs with 'a' values of -15 and +15, the critical
      structure objectives were defined in terms of maximum EUDs with 'a' values of'1',
      '5' and '10'. Both dose-volume and gEUD-based VMAT plans used 6MV, 280 degree
      dual arcs. The prescription doses for all cases were 70Gy to PTV1, 60Gy to PTV2
      and 54Gy to PTV3 delivered in 33 fractions. The critical structures included
      cord, parotids, brainstem, and esophagus. The critical structure sparing in
      physical and biological plans were assessed using dose- volume indices, including
      D2, D50, and Dmean, and MUs and treatment delivery times. RESULTS: PTV coverage
      obtained by both dose-volume and biological-based optimization were generally
      very similar, although the target conformality was slightly better for dose
      volume based VMAT plans. The gEUD-based plans produced superior critical
      structure sparing, yielding up to 55% reduction in cord D2, 35% reduction in
      parotids Dmean and 14% reduction in brainstem D2 as compared to dose-volume based
      plans. On average, MUs for gEUD-based plans increased by 12.1%, 18.8% and 21.3%
      for 'a' values of'1', '5' and '10' respectively compared to dose-volume based
      VMAT plans with no change in delivery times. CONCLUSIONS: This study showed that
      the biology-based optimization has ability to generate H&N VMAT plans with
      significantly improved critical structure sparing with generally similar
      target(s) coverage as compared to the dose-volume based physical optimization.

PMID- 28517051
TI  - SU-E-T-593: VMAT Vs. IMRT for Treatment of Neoplasms of the Brain: Dosimetric
      Quality and Delivery.
AB  - PURPOSE: A retrospective study was performed to determine any dosimetric or
      delivery benefits for treatment planning with intensity-modulated radiotherapy
      (IMRT) versus volumetric-modulated arc therapy (VMAT) for the treatment of brain
      neoplasms. METHODS: Eighteen patients treated with modulated brain radiotherapy
      treatments were included in this study (primary treatment volumes of 15.3 to
      374.9 cc). IMRT and VMAT plans were generated for each patient using the same
      criteria for prescription coverage and normal tissue sparing. IMRT optimizations
      ranged from five to seven fields and VMAT from two to four arcs. Plans were
      generated with Varian Eclipse treatment planning system utilizing AAA-8615 dose
      calculation algorithm. RESULTS: VMAT optimizations provided limited dosimetric
      advantages versus IMRT. VMAT provided superior treatment volume coverage (volumes
      receiving 95%, 100% of prescription dose (V95%, V100%)) over IMRT, but
      differences were not statistically significant (paired t-test p > 0.05). Relative
      maximum dose values, conformity and homogeneity indices also exhibited no
      statistical differences. IMRT plans resulted in similar mean brain minus
      treatment volume (Brain- TV) dose (mean = 1460.1 vs. 1506.3 cGy; p = 0.056). The
      volume of Brain- TV receiving 40Gy was lower for VMAT than IMRT (average = 38.96
      vs. 44.97 cc; p = 0.050). Maximum skin dose was lower for VMAT (mean = 4568.8 vs.
      5063.3cGy; p = 0.006), as well as skin V20Gy (6.56% vs 7.69%; p = 0.027) and
      V40Gy (0.56% vs. 0.35%; p = 0.017). VMAT plans required fewer fields along with
      fewer MU than IMRT (mean = 388.2 vs. 721.1 MU, respectively), allowing for
      approximately 20% faster delivery times. CONCLUSIONS: VMAT treatments
      significantly reduced treatment time due to reduced MU and fewer fields. Certain
      skin and Brain-TV high dose spread parameters were superior for VMAT as compared
      to IMRT plans. All other dosimetric parameters tested were statistically
      equivalent for VMAT and IMRT techniques.

PMID- 28517052
TI  - SU-E-T-564: Radiation Therapy for Lung Cancer: A Treatment Planning Comparison
      among Fixed Field IMRT, Coplanar and Noncoplanar Arcs Volumetric Modulated Arc
      Therapy.
AB  - PURPOSE: A treatment planning study was performed to compare fixed field IMRT,
      coplanar and noncoplanar VMAT. METHODS: Treatment planning CT scans of three lung
      cancer patients with small (2244cc), medium (2845cc) and large (3531cc) lungs
      were used to create simulated patient cases. For each simulated patient, three
      spherical tumors (GTV) of varying diameters: 1, 3, 5 cm were contoured onto lung
      CT scans. The ITV was set as GTV+2 cm and the PTV was set as ITV+1 cm. The
      location of the tumor was set in the right middle lobe of lung. For each patient
      scenario, the IMRT (nine static fields), single coplanar arc VMAT and 5
      noncoplanar arcs VMAT treatment plans were generated using Pinnacle treatment
      planning system. The arcs of noncoplanar VMAT were set at -30 degrees  (clockwise
      and counterclockwise), 0 degrees  and 30 degrees  (clockwise and
      counterclockwise). Thetreatment plans were evaluated by calculation of V100%,
      V80%, V50% and V20%, DVH of dose constrain rings (DCR) at PTV+1cm, +2cm, +3cm,
      +4cm and Paddick Conformity Index (CI: 0-1 best) and Gradient Index (GI:the
      smaller the better). RESULTS: The V100% and V80% were similar for all the plans
      but the V50% and V20% were the largest for IMRT, and the smallest for noncoplanar
      VMAT. The noncoplanar VMAT had larger V<20but smaller V>20 for all the DCRs
      comparing to the other two plans. The CI of noncoplanar VMAT was slightly larger
      than the other two plans. The GI was the smallest for noncoplanar VMAT and the
      largest for IMRT for all the simulation scenarios. CONCLUSIONS: The noncoplanar
      VMAT consistently provides high dose conformity to the target and low dose to
      healthy tissue. The noncoplanar VMAT has larger low dose volume while smaller
      high dose volume comparing to IMRT and coplanar VMAT.

PMID- 28517053
TI  - SU-E-T-604: Inter Planner Dosimetric Variations in IMRT.
AB  - PURPOSE: To study inter-planner variations in IMRT dosimetry with identical dose
      prescription in IMRT optimization for estimation of quality of treatment plans by
      using dose volume histogram (DVH). METHODS: Five treatment planners: p1, p2, p3,
      p4 and p5 with Eclipse TPS and Varian accelerator were chosen. The 3D data sets
      including PTV and OAR of a prostate case was sent with instructions for beam
      orientations, energy and dose-volume constraints. Each planner performed the
      treatment planning process with inhomogeneity corrections by using the same dose
      constraints. DVH and isodose distributions were compared to examine the inter
      planner variations. RESULTS: There were large variations in the IMRT plans
      reflected by the DVH among the planners even with identical dose constraints in
      IMRT optimization. Clinically constraint#1 (D95-V95) dose criteria could be
      considered as the most important one. Two planners did not meet the criteria,
      whereas planner 4 met all of the dose criteria for PTV and OARs. The inter
      planner variations in PTV as large as 20% were found in this study. Every time
      optimization is performed even with the same constraints, the DVH output was
      significantly different due to the differences in constraint weights.
      CONCLUSIONS: There exists a significant inter planner variation for all cases
      studied indicating that even for the same constraints the outcome cannot be
      guaranteed to be identical due to cost function convergence. It seems feasible to
      control the over-dosage for all planners. However we see large deviations in
      plans with respect to different constraints. Planner 4 met all the dose criteria
      for PTV and OARs indicating that it is possible to plan and meet all the dose
      criteria. This approach could be used as gold standard.

PMID- 28517054
TI  - SU-E-T-575: To Analyze the Clinical Impact of Esophageal Sparing on Treatment
      Plans for Patients with Grade 3 Esophagitis.
AB  - PURPOSE: To analyze the clinical impact of esophageal sparing on treatment plans
      for patients with grade 3 esophagitis. METHODS: The treatment plans of 8 patients
      (project total: 20 patients) who were treated with IMRT and exhibited stage 3
      esophagitis were re-planned to give a simulated clinical plan with dose
      distribution that mirrored our current clinical practice (74Gy to the target, and
      5mm margins), and a plan that emphasized esophageal sparing. Doses to the
      esophagus, heart, cord, lung and PTV were compared. RESULTS: Comparing the
      esophageal sparing plan to the simulated clinical plan, the mean reduction in
      esophageal volume receiving 50, 55, 60, 65, and 70Gy were 2.0, 3.2, 5.0, 7.2, and
      10.9 cm3 , respectively. The mean reduction in the continuous length of esophagus
      receiving 50, 55, 60, 65, and 70Gy were 12, 24, 38, 40, and 47mm, respectively.
      The associated reduction in dose to 90% and 95% of the PTV was 2.2 and 3.8Gy,
      respectively. Of the 8 patients examined, 2 showed a significant decrease in PTV
      coverage (4.6Gy, 12.3Gy for 90% of PTV), 4 showed decreases under 1.1Gy, but 2
      showed an increase of 1.4Gy and 0.5Gy for 90% PTV. Cord dose was maintained below
      50Gy, and there was a slight increase in mean heart dose and mean lung dose of
      2.4Gy, and 2.7Gy, respectively. Data will also be presented comparing these plans
      with the actual treated plans (for which the patients had grade 3 esophagitis)
      and plans that emphasize PTV coverage. CONCLUSIONS: Treatment planning to
      emphasize esophageal sparing can reduce the volume and continuous length of the
      esophagus which receives high doses. There is some associated modest reduction in
      PTV coverage. In summary, in many cases esophageal sparing can be accomplished
      for lung cancer cases while maintaining adequate PTV coverage, although there is
      variability between patients.

PMID- 28517055
TI  - SU-E-T-586: Comparison between CT-and FLT-PET-Defined Target Volumes and
      Dosimetry for Radiotherapy Planning in Esophageal Carcinoma.
AB  - PURPOSE: To study the advantage of fused 3-deoxy-3-18F-fluorothymidine (FLT)
      positron emission tomography (PET) and computed tomography (CT) images on
      radiotherapy planning for esophageal carcinoma patients . METHODS: Ten patients
      with esophageal carcinoma were referred for radiotherapy. Each patient underwent
      CT and FLT PET scan for simulation plan in the same treatment position. FLT PET
      images were coregistered with CT images. GTVCT was initially performed on CT
      images, GTVPET-CT were automatically segmented on FLT PET/CT images using a fixed
      threshold values at 1.4. Two kinds of treatment plans were designed based on
      GTVCT and GTVPET-CT. The radiation dose was prescribed as 60 Gy in 30 fractions.
      The dose-volume parameters of target volume and normal tissues, CI and HI of
      based on the GTVPET- CT and GTVCT were compared. RESULTS: The mean GTV delineated
      on CT and PET- CT were 39.28 cms and 34.48 cms , respectively . The values for
      mean lung dose, total-lung volume receiving =5, = 10, = 20 and = 30Gy;mean heart
      dose, heart volume receiving =30Gy and normal tissues of plan based on the GTVPET
      CT were significant lower than plan based on the GTV-CT. CONCLUSIONS: In our
      study, FLT PET use has an impact on target delineation for radiotherapy planning.
      GTVPET-CT is significantly smaller than GTVCT with a mean volume reduction of
      16%. CT and FLT/PET image fusion appeared to have an advantage on dose reduction
      of organ at risk in radiotherapy planning of esophageal carcinoma.

PMID- 28517056
TI  - SU-E-T-597: Influence of Smoothing Parameters on Dynamic IMRT Plan Quality and
      Deliverability.
AB  - PURPOSE: To study the impact of different smoothing parameters on IMRT plan
      quality and deliverabilityMethods: Five previously treated patients of carcinoma
      cervix were chosen. Planning target volume (PTV) and organ at risk (OAR) i.e.
      bladder and rectum were contoured. In each case, five different dynamic IMRT
      plans with 6MV photon beam were created in eclipse TPS for Varian 2300C/D linear
      accelerator. During optimization, dose volume constraints and priorities were
      kept constant and smoothing parameters were varied as follows: 10/5, 40/30 (TPS
      default value), 80/60, 100/80 and 200/150 in x/y direction. Total dose was
      5040cGy in 28 fractions and prescribed at 95% isodose. Plan quality was analyzed
      by means of coverage index (CI=PTV covered by prescription dose/PTV), OAR mean
      doses and total monitor units (MUs) required to deliver a plan. In each case,
      deliverability of treatment plans were verified with I'matriXX ion-chamber array
      and compared with TPS dose-plane using gamma index of 3% dose difference and 3mm
      distance to agreement criteria. RESULTS: The CI values were 0.9435+/-0.032,
      0.9418+/-0.034, 0.9380+/-0.041, 0.9330+/-0.047 and 0.8681+/-0.072 for 10/5,
      40/30, 80/60, 100/80 and 200/150 in x/y direction. PTV dose maximum decreases
      with the increase of smoothing parameters and values were 5724.38+/-106.08
      5723.30+/-131.60, 5708.44+/-1 16.74, 5697.92+/-116.82 and 5587.50+/-189.50cGy.
      The bladder mean doses were 4027.46+/-630.40, 3821.62+/-420.62, 3819.58+/-427.08,
      3813.42+/-435.02 and 3814.78+/-438.0cGy. Rectum mean doses were 3839.88+/-466.02,
      3835.52+/-473.18, 3837.52+/-472.88, 3839.10+/-471.20 and 3918.94+/-469.76cGy.
      Similarly, Total MUs were 1588+/-205, 1573+/-214, 1513+/-274, 1456+/-335 and
      1219+/-68. Gamma pass rate increases with the increase of smoothing parameters
      and values were 99.16+/-0.21%, 99.07+/-0.19%, 99.24+/-0.28%, 99.29+/-0.29% and
      99.75+/-0.15%. CONCLUSIONS: When smoothing parameters decreased below TPS default
      value, plan quality increases, but deliverability decreases. If smoothing
      parameters increased above TPS default value, deliverability increases but plan
      quality decreases. Total MU decreases with the increase of smoothing parameters.
      Therefore, it's a trade-off between plan quality and deliverability which needs
      to be justified clinically.

PMID- 28517057
TI  - SU-E-T-568: Hippocampus and Neural Stemcell Sparing Using Proton Therapy in Whole
      Brain Irradiation.
AB  - PURPOSE: To investigate feasibility of using proton therapy (PT) in neural
      stemcell sparing and to compare its dosimetric advantage to IMRT. To investigate
      the robustness of the proton plan in hippocampus sparing by introducing
      translation and rotation errors in treatment plan. METHODS: Hippocampal
      neurogenesis directly correlates to memory and other cognitive functions.
      Compared to the traditional whole brain (WB) uniform irradiation, Photon
      Intensity-Modulated-Radiation-Therapy (IMRT) can reduce hippocampal dose somewhat
      but limited by its beam exit dose. Pinnacle and Eclipse were used, respectively,
      for IMRT and PT planning (30Gy in 10 fractions) for hippocampal neural stemcell
      sparing WB irradiation. Both hippocampus and neural stemcell regions were
      contoured as avoidance region. Similar to RTOG0933, the target was defined as the
      WB subtracted by 5 mm expansion of the avoidance region. Other organs-at- risk
      (OARs) includes lenses, eyes, optical chiasm, optical nerves, brainstem and
      parotids. Twelve coplanar beams were used in IMRT plans with 2.5mm MLC width.
      Objectives were specified to maximize target coverage and reduce dose to
      avoidance region and to other OARs. There were 9 non- coplanar proton beams that
      include 2 pairs of patch fields, 1 pair of match fields and 4 open fields. Distal
      blocking was used in 5 beams. RESULTS: Both plans' target coverage was scaled at
      70% target covered by 30Gy. Plan comparison between proton and IMRT are,
      respectively, as follows: Target D2 (36.2, 37.3Gy); Mean dose to avoidance region
      (0.96, 5Gy); mean doses to left-lens (0.21, 3.35Gy); mean doses to right-lens
      (0.25, 3.57Gy); mean dose to left-parotid (0.82, 9.57Gy) and right-parotid (0.11,
      11.6Gy). Similar dose distribution found in brainstem, eyes and optical nerves
      and chiasm for both proton and IMRT plans. CONCLUSIONS: Proton plan demonstrated
      dosimetric advantage in neural stemcell and hippocampus sparing than IMRT plan.
      The proton plan is robust from translation and rotation setup errors.

PMID- 28517058
TI  - SU-E-T-608: Integrated Beam Orientation and Fluence Map Optimization in Radiation
      Therapy Treatment Planning.
AB  - PURPOSE: To efficiently select high-quality coplanar or non-coplanar beam
      orientations for IMRT treatments while formally and explicitly incorporating the
      effect of the selected beam orientations on the quality of the dose distribution
      obtained by the treatment plan optimization model. METHODS: Beam orientation
      models consider a discrete set of potential coplanar and/or non-coplanar beam
      locations around the patient. A new greedy algorithm is proposed to solve a model
      that integrates beam orientation optimization (BOO) and fluence map optimization
      (FMO). The algorithm iteratively adds beams to a FMO model. In each iteration, an
      attractiveness measure is associated with each remaining candidate beam
      orientation. This attractiveness measure is based explicitly on an optimal dose
      distribution that allows only the currently selected set of beams to be used.
      Several alternate attractiveness measures are considered which use either first
      order information or both first and second-order information. Performance of the
      algorithm was assessed on a clinical lung cancer case. RESULTS: The developed
      beam selection algorithm was applied to a lung cancer case using either coplanar
      beams or both coplanar and non-coplanar beams. In the coplanar case, beam
      orientations were found that produce a superior dose distribution to that using
      an equal number of equi-spaced beams. In the non-coplanar case it was found that
      fewer beams were needed to produce a dose distribution of comparable quality to
      that found in the coplanar case. CONCLUSIONS: The developed solution approach
      showcases the potential benefits of integrating different steps in the treatment
      plan optimization process. By integrating the BOO and FMO models, treatment plan
      quality was explicitly incorporated into the beam selection process. BOO can be
      automated and implemented efficiently, which eliminates the guesswork involved in
      manually adjusting beam orientations in IMRT treatment planning.

PMID- 28517059
TI  - SU-E-T-579: Dosimetric Benefits of Online Adaptive Replanning for Post-Operative
      Radiation Therapy of Prostate Bed.
AB  - PURPOSE: To demonstrate the dosimetric benefits of using an online adaptive
      replanning scheme to address interfractional variations in radiotherapy of
      prostate bed. METHODS: We have previously developed an online adaptive replanning
      tool (RealART, Prowess Inc.) aiming to address interfractional variations
      including organ deformation and rotation. Using this tool, we analyzed a total of
      102 daily pre-treatment CTs acquired using an in-room CT (CTVision, Siemens) for
      10 patients treated with post-operative IMRT of prostate bed. The PTV was assumed
      to be the volume enclosed by the 95% prescription isodose surface generated for
      the conventional four field box. On each daily CT set, contours of the PTV,
      rectum and bladder were generated by populating the planning contours using an
      auto-segmentation tool based on deformable registration (ABAS, Elekta) with
      manual editing. Four plans were generated and compared: (1) IGRT (repositioning)
      plan by copying the original plan with aligning the anterior rectal wall from the
      daily CT to that of the planning CT, (2) IGRT plan by copying the original plan
      with aligning the surgical clips, (3) online adaptive plan by tailoring the
      original plan to conform to the anatomy of the day, and (4) a new plan re-
      optimized based on the daily anatomy. RESULTS: The adaptive and re- optimization
      plans are in general superior than the two repositioning plans in terms of both
      target coverage and critical structure sparing. For example, the averages of dose
      volume quantities for all daily CTs are: rectum V45Gy 55.7+/-18.0% (one standard
      deviation), 57.3+/-17.5%, 48.2+/-11.8%, 42.5+/-9.6%; rectum V60Gy 31.8+/-20.3%,
      34.0+/-16.6%, 22.6+/-9.7%, 16.5+/-7.4%; bladder V45Gy 30.0+/-11.9%, 39.5+/-24.2%,
      37.6+/-16.8%, 36.5+/-16.2%; bladder V60Gy 17.4+/-9.2%, 25.4+/-18.1%, 24.7+/
      12.7%, 23.9+/-12.0%; PTV V100 81.9+/-16.6%, 88.7+/-7.9%, 92.9+/-4.6%, and 94.6+/
      2.4% for the above (1)-(4) plans, respectively. CONCLUSIONS: The online adaptive
      replanning scheme is effective to account for interfractional variations in post
      operative radiotherapy of prostate bed. This work is supported partially by MCW
      Cancer Center Fotsch Foundation.

PMID- 28517060
TI  - SU-E-T-590: Procedure for Verification and Inter-Comparison of IMRT Beam Models.
AB  - PURPOSE: The implementation of an accurate beam model is an integral part of the
      commissioning of any planning system. This process is especially challenging in
      the case of IMRT beam models owing to the complexity of small field sizes and MLC
      leaf-end and tongue-and-groove effects. The question of how to judge the quality
      of an IMRT beam model in comparison with other versions of the same model is
      central to this work. METHODS: We make an important distinction between
      evaluation of the beam model and evaluation of the optimization routine that is a
      part of any IMRT planning system. The H-shaped target used in this work has
      several important features: it can only be covered by segments with small field
      size, for which all leaf design effects are important, and it has the overall
      dimensions of a common IMRT target. The procedure for inter-comparison of two
      IMRT beam models (old and new) involves the generation of two plans optimized
      with each beam model using identical IMRT prescriptions. Both plans are
      subsequently delivered on a solid water phantom with film located in two parallel
      planes with a small-volume ionization chamber inserted in the center. RESULTS:
      Four dose calculations are performed, such that each plan is calculated with
      either of the two beam models. The four dose distributions are subsequently
      compared with the two film measurements using gamma analysis. In addition, the
      absolute dose measured in the center of the dose distribution is compared with
      the calculated value. A score is assigned to each beam model based on the
      results. CONCLUSIONS: Using the procedure outlined in this presentation,
      different versions of an IMRT beam model can be compared and scored for quality.
      Adoption of a unified strategy for beam model inter-comparison can greatly
      facilitate the evaluation and commissioning of IMRT beam models.

PMID- 28517061
TI  - SU-E-T-611: Utilizing Machine Learning Techniques for Beam Angle Selection in
      Radiation Treatment Planning.
AB  - PURPOSE: To utilize machine learning techniques within beam angle optimization to
      determine an optimal Intensity-modulated radiation therapy (IMRT) beam angle set.
      METHODS: The input data were derived from a collection of equally-spaced seven
      beam plans (e-plans) generated using the Pinnacle. This collection of e-plans
      contains all 72 beam angles corresponding to 5 degree spacing, and the dose
      delivered to patient tissues from each of these 72 angles was extracted to
      generate p-scores. Equally-spaced beam sets are commonly used in clinical
      practice, so this set of plans not only provides initial input data for our beam
      angle selection (BAS) procedure, but also provides a good set of benchmarks
      against which treatment improvement may be measured. A beam set scoring function
      was developed based on a weighted sum of overdose/underdose criteria. The Nested
      Partitions (NP) global optimization framework is then utilized to guide a sample
      based search for the global optimal of the beam angle space. In our NP-based
      approach to BAS, a single sample is a 7-beam set satisfying beam spacing
      constraints. A fast scoring method based on the e-plan single-beam dose data was
      used to obtain an initial approximate score (c-score) and a set of dose component
      scores for each beam set. Machine learning techniques were then employed to
      predict each dose component, and these values were used to compute a predicted
      score. RESULTS: The average improvements in p-scores for 5 cases were 43%, 29%
      and 11% comparing to default eplan, best eplan and conventional NP (without ML).
      10%, 12% and 15% improvement was achieved for sparing of spinal cord, brain stem
      and oral mucosa, respectively. CONCLUSIONS: Machine learning tools provide an
      effective technique for rapid high-quality approximate scoring for beam angle
      sets in IMRT. This approximation process leads to excellent beam sets when
      embedded within the NP global optimization framework. This work was supported in
      part by a grant from the NIH/NCI CA130814.

PMID- 28517062
TI  - SU-E-T-615: Quantifying the Benefit of Adaptive Fractionation.
AB  - PURPOSE: To quantify the benefit of adaptive fractionation, through both
      theoretical test cases and patient data. METHODS: We consider the effect of
      delivering a different fraction size based on the changes observed in the patient
      anatomy. Given that a fixed prescription dose must be delivered to the tumor over
      the course of the treatment, we find that adaptively varying the fraction size
      results in a lower cumulative dose to a primary organ-at-risk (OAR). We construct
      a one dimensional theoretical example by randomly varying the distance between
      the tumor and OAR, and simulate the benefit of adaptive fractionation in such a
      setting. Next, we test our methodology using contoured daily CT images from 5
      prostate patients. RESULTS: For the theoretical example, we found about a 10%
      decrease in dose to the OAR when using a uniformly distributed motion model and a
      20% daily fraction size deviation. In general, the amount of decrease in dose to
      the OAR varied significantly (5-85%) for these theoretical test cases depending
      on the amount of motion in the anatomy, the number of fractions, and the range of
      fraction sizes allowed. Preliminary results from the prostate patients indicate
      an average reduction in dose to the rectum of 1.4%, 3.5%, and 7.0% when using
      20%, 50%, and 100% daily fraction size deviations, respectively. CONCLUSIONS:
      Qualitatively, the theoretical example indicates that adaptive fractionation is
      beneficial for disease sites in which there is significant inter-fractional
      motion. We also expect greater benefit when using many fractions and allowing for
      large daily fraction size deviations. For the prostate disease site in
      particular, we find that adaptive fractionation is beneficial only when allowing
      large daily fraction size deviations. Further research quantifying the gain for
      disease sites that exhibit significant inter-fractional motion, such as rectal
      and cervical cancers, would be useful. Partially supported by Siemens.

PMID- 28517063
TI  - SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical
      TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT).
AB  - PURPOSE: Several planning strategies are available for hippocampal- avoidance
      whole-brain radiotherapy (HA-WBRT) following RTOG protocol 0933, but have yet to
      be compared on a common set of patient data. In this inter-institutional
      investigation, we evaluate three modalities likely to be employed by protocol
      participants; step-and-shoot IMRT, volumetric modulated arc therapy, and helical
      tomotherapy. A common set of patients is used for comparison, including
      credentialing and successfully accrued patients. METHODS: Eight patient datasets
      were selected and de-identified prior to planning. Structures were contoured by
      physicians per protocol using fused MRI datasets. Three plans were generated for
      each dataset: Philips Pinnacle 9-field non-coplanar IMRT using protocol
      recommended beam parameters, Varian's RapidArc using two coplanar arcs, and
      Accuray's TomoTherapy using a 1cm jaw width. With the goal of meeting the
      compliance criteria outlined in RTOG 0933 (target coverage and dose limits to the
      hippocampus and optic structures), three planners independently planned each
      modality without prior knowledge of the patient's other plans to reduce bias. The
      three plans for each patient were compared according to the protocol's dosimetric
      compliance criteria. A homogeneity index was also computed to compare target dose
      uniformity. RESULTS: All plans achieved the protocol dose criteria, except for
      one RapidArc plan with slightly inferior dose to the optic chiasm. TomoTherapy
      offered superior dose homogeneity for all patients. For the two linac based
      methods, RapidArc was found to provide dose homogeneity at least as good as, and
      in most cases superior to, 9-field step-and-shoot IMRT. CONCLUSIONS: Helical
      TomoTherapy offers superior dose homogeneity for HA-WBRT following RTOG 0933.
      Compared to step-and-shoot IMRT, volumetric modulated arc techniques, such as
      RapidArc, can offer improved homogeneity for HA- WBRT and are generally more
      efficient/expeditious to deliver than the noncoplanar 9-field arrangement
      recommended by the protocol, which uses 7 separate couch angles.

PMID- 28517064
TI  - SU-E-T-592: Comparison of Low Dose Volume and Integral Dose in Rotational Arc
      Radiation Therapy Modalities.
AB  - PURPOSE: To compare low dose volume and integral dose of various rotational arc
      radiation therapy modalities, including helical tomotherapy (HT) and other
      volumetric modulated arc therapies (VMAT). METHODS: A digital cylindrical phantom
      and an anthropomorphic pelvic phantom were used in the study. HT treatment was
      planned on TomoTherapy Planning Station (Accuray) and VMAT plans were generated
      on Pinnacle (Philips) and Eclipse (Varian). Same objectives and criteria were
      used for all the planning tasks. Tomotherapy plans were made with both 1cm jaw
      and 2.5cm jaw. Pinnacle SmartArc and Eclipse RapidArc plans used 1 arc and 2
      arcs. Plan quality was evaluated by dose-volume histograms, conformity index
      (CI), and heterogeneity index (HI). V10% and V20% of body were used in
      quantifying low dose volume. Integral doses were computed for each plan and
      compared. Dose profiles across the target center were retrieved to show the rate
      of dose falls off. RESULTS: All arc TPS generated clinically acceptable plan with
      comparable target CI and HI. The V20% of body of the cylindrical phantom case
      were 3551cc, 4054cc, 3375cc, 3438cc, 3714cc and 3679cc for tomotherapy 1 cm and 2
      cm jaw, SmartArc 1 arc and 2 arc, and RapidArc 1 arc and 2 arc plans,
      respectively. The integral doses were 19.67, 22.78, 18.68, 18.50, 19.78 and 19.73
      Joule, respectively. For the anthropomorphic phantom, the integral doses were
      81.69, 102.77, 84.5 and 82.5 Joule for tomotherapy 1cm, 2cm, SmartArc 1arc and
      RapidArc 1arc, respectively. Dose profiles showed tomotherapy 1cm plan had
      similar longitudinal penumbra as SmartArc and RapidArc, while tomotherapy 2.5cm
      plan produced significant broader penumbra. CONCLUSIONS: Similar low dose volume
      and integral dose are found in SmartArc, Rapid Arc, and as well as helical
      tomotherapy plan of 1cm jaw. Tomotherapy plans of 2.5cm jaw, however, shows
      higher low dose volume and integral dose.

PMID- 28517065
TI  - SU-E-T-563: Which is More Important in IMRT Planning: The Number of Beam Angles
      or the Number of MLC Segments?
AB  - PURPOSE: Rotational IMRT delivery has attracted considerable attention. Some
      people believe that rotational IMRT should provide better plan quality with more
      beam angles to irradiate the target. In this work, we will study the impact of
      the number of fields and MLC segments on the IMRT plan quality. METHODS: The RPC
      IMRT benchmark phantom was used in the IMRT planning. The number of gantry angles
      used ranges from 3 to 90 with various numbers of segments. All IMRT plans were
      created using Pinnacle3 DMPO module using the same objectives. The final
      objective value is used to quantify the plan quality. RESULTS: When the number of
      beam angles is more than 3, the objective value decreases dramatically with
      increasing segments till the number reaches around 60. When the number of
      segments is small, the availability of more beam angles can clearly improve the
      IMRT plan quality. However, such a plan quality improvement becomes less dramatic
      as the number of total segments increases. For example, when the number of
      segments is 30, increasing the number of beam angles from 3 to 18 can reduce the
      objective value by 75%. Such a reduction reduces to 44% when the number of
      segments increases to 60. Single-arc VMAT plans showed less desirable plan
      quality comparing to fixed-field IMRT plans using the same number of beam-angles
      and segments. CONCLUSIONS: The number of segments has dramatic impact on the IMRT
      plan quality when the number of fields is more than 5. If enough segments are
      used in IMRT planning, increasing the number of beam angles can only slightly
      improve the plan quality. The increase in plan quality led by increasing beam
      angles can be limited by the MLC motion constraint for rotational IMRT delivery.

PMID- 28517066
TI  - SU-E-T-603: Influence of PTV Delineation at Air Cavity Interface on Tomotherapy
      Plan Quality.
AB  - PURPOSE: To determine if different ways in PTV delineation at an air cavity
      interface yield differences in overall plan quality and treatment efficiency
      Methods: Three different PTVs were used for treating a patient whose CTV
      surrounded a large air cavity created by a resected hard palate. The CTV lined
      the surface of the air cavity while PTV1 included the entire air cavity, PTV2
      extended 4mm from the surface of the cavity into air, and PTV3 was reduced 4mm
      within the surface of the cavity. Tomotherapy plans were generated for all three
      PTVs. During each planning, all constraints to target and normal structures were
      kept constant along with the number of optimizations. Same planning process was
      repeated on a head and neck digital phantom with mock target, normal structures
      and cavity. RESULTS: Three treatment planning approaches showed no significantly
      different target coverage in terms of minimum or maximum dose to their respective
      PTVs. All plans attained 95% coverage of the CTV and PTV by 100% of the
      prescription. The conformity index (CI) of the plans delivered to PTV1, PTV2, and
      PTV3 were 1.09, 1.11, and 1.18, respectively. The skin, optic nerves, brainstem
      and spinal cord all received similar maximum dose to their respective volumes for
      each plan within 1Gy. The monitor units required for each treatment plan were all
      within 6% of one another with PTV1 having the highest. For head and neck phantom,
      the CIs of three plans were 1.05, 1.21, and 1.18, respectively. The coverage of
      the phantom CTV and sparing of normal structures were nearly equivalent. The
      total treatment times were identical. CONCLUSIONS: Tomotherapy planning is able
      to deliver dose to a head and neck PTV containing a large air cavity without
      compromising target coverage, sparing of normal tissues, or delivery time.

PMID- 28517067
TI  - SU-E-T-574: Volumetric Modulated Arc Therapy for Prostate Radiation: A Dosimetric
      Comparison between VMAT Techniques and Fixed-Beam IMRT.
AB  - PURPOSE: To compare prostate radiation planning using four VMAT techniques and
      IMRT on plan quality and dose delivery efficiency. METHODS: The four VMAT
      techniques are: 1) Monaco VMAT (Version 2.03.01, CMS Inc., MO); 2) RapidArc
      (Eclipse Version 10.0, Varian Medical System Inc., CA); 3) SmartArc (Pinnacle
      Version 9.0, Philips Radiation Oncology Systems, WI) and 4) helical TomoTherapy
      (TomoTherapy Version 3, Accuray Inc., CA). The IMRT planning employed 7-field
      fixed gantry on Pinnacle. Single full-arc plan using each technique was generated
      for five prostate cases. All plans were prescribed to 70 Gy (2.5 Gy/fx) to 95%
      PTV using 6 MV photon beams to achieve same PTV coverage and similar OAR sparing.
      The quality of dosimetric plans was evaluated using metrics: target coverage,
      heterogeneity index (HI), target/organ mean/max/min doses, EUD, dose-volume
      histogram, etc. RESULTS: All VMAT plans are capable of delivering adequate target
      dose with equal or better OAR sparing than IMRT plans. The average mean PTV doses
      were 72.8, 73.1, 71.0 and 72.5 Gy with HIs of 1.10, 1.08, 1.03 and 1.05 for the
      Monaco, RadipArc, SmartArc and TomoTherapy plans respectively. In low dose range,
      TomoTherapy resulted in the highest V10 and V20 while V70 and V60 were generally
      lower compared to other plans. Generated on the same platform, the SmartArc plans
      were slightly more conformal (CI=1.04 vs 1.08) and less heterogeneous (HI=1.02 vs
      1.04) with better OAR sparing compared to IMRT plans. The average required MUs
      were 817 (Monaco), 735 (RapidArc), 798 (SmartArc) and 4986(TomoTherapy), compared
      to 876 MUs for the IMRT plans. CONCLUSIONS: All single-arc VMAT techniques under
      study improve normal tissue sparing with more efficient dose delivery compared to
      prostate IMRT plans. RapidArc plans require least MUs while SmartArc provided
      most homogenous plans. All VMAT plans demonstrate significantly reduced MUs to
      achieve comparable dosimetric plans compared to Tomotherapy.

PMID- 28517069
TI  - SU-E-T-596: Choroidal Metastases Irradiation with Volumetric Modulated Arc
      Radiotherapy.
AB  - PURPOSE: Intraocular metastases are present in up to 10% of patients with
      systemic malignancies. With tumor cells spreading hematogenously, the posterior
      choroid is frequently involved because of its rich vasculature. We treated a
      woman who developed bilateral choroidal metastases from breast cancer. For the
      patient, we designed three radiotherapy techniques. The study was to find the
      dosimetric differences between them. METHODS: For the patient with bilateral
      choroidal metastases, three-dimensional conformal radiotherapy (3D-CRT), inverse
      intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy
      (V-MAT) plans were designed. The prescription dose was 60 Gy in 30 fractions. The
      dose distribution in the target, the dose to the organs at risk, total MU and
      delivery time were compared. RESULTS: In 3D-CRT, IMRT and V-MAT plans, the volume
      of target in 100% prescription dose were 92.5%, 93.3% and 92.0% respectively. V
      MAT plan showed the best conformity and homogeneity in target. IMRT plan showed a
      better homogeneity than 3D-CRT plan. In 3D- CRT, IMRT and V-MAT plans, the max
      doses on left lens were 975.3 cGy, 739.9cGy, 870.2 cGy respectively. The max
      doses on right lens were 929.9 cGy, 802.9 cGy and 889.0 cGy respectively. V-MAT
      plan showed the lowest value for the max dose on left optic nerve and the lower
      value for the right one compared to 3D-CRT plan. The MUs were 386, 973, 709 and
      the delivery times were 10 min, 14min and 1.6 min respectively in 3D-CRT, IMRT
      and V-MAT. V-MAT could significantly reduce the delivery time. CONCLUSIONS: V-MAT
      plan showed the best conformity and homogeneity in target. IMRT showed the lowest
      value in the max doses to lenses though the delivery time was longest. Overall, V
      MAT showed a similar or better dose distribution, and most importantly, improved
      treatment delivery efficiency. With the results, V-MAT technology could be
      expected to choroidal metastases.

PMID- 28517068
TI  - SU-E-T-585: Application of IMAT in Non-Small-Cell Lung Cancer with Simultaneously
      Integrated Boost Radiation Therapy.
AB  - PURPOSE: To compare and analyze the characteristics of intensity-modulated arc
      therapy(IMAT) versus fixed-gantry intensity-modulated radiotherapy(IMRT) in
      treatment of non-small-cell lung cancer. METHODS: Twelve patients treated in our
      radiotherapy center were selected for this study. The patient subsequently
      underwent 4D-CT simulation.Margins of 5 mm and 10mm were added to the ITV to
      generate the CTV and PTV respectively. Three treatment plans (IMRT,one single arc
      (RA1),double arcs (RA2))were generated with Eclipse ver.8.6 planning systems.
      Using a dose level of75Gy in 15fractions to the ITV,60Gy in 15fractions to the
      CTV and 45Gy in 15fractions to the PTV respectively. The target and normol tissue
      volumes were compared, as were the dosimetry parameters. RESULTS: There were no
      significant differences in CI of ITV,PTV, HI of ITV,CTV and PTV,
      V5,V10,V15,V20,V25,V30,V45,V50 of total-lung and mean lung dose (all p>0.05).
      However, the differences were significant in terms of CI of CTV, V5 of B-P (all
      p<0.05). On the MU, IMRT=1540MU,RA1=1006 MU and RA2=1096 MU. (F=12.00,P=0.000).On
      the treatment time, IMRT= 13.5min,RA1= 1.5min, and RA2=2.5 min (F=
      30.11,P=0.000). CONCLUSIONS: IMAT is equal to IMRT in dosimetril evaluation. Due
      to much less Mu and delivery time,IMAT is an ideal technique in treating patients
      by reduceing the uncomfortable influnce which could effect the treatment.

PMID- 28517070
TI  - SU-E-T-567: Improve Dose Conformity with IMRT Using Shorter Source to Tumor
      Distance.
AB  - PURPOSE: To reduce the potential of late toxicity (tissue necrosis and cognitive
      function loss) from brain radiotherapy, we studied a novel planning technique for
      MLC-equipped linear accelerators (LINACS) that reduces the high doses delivered
      outside the PTV, enhancing radiation dose conformity. METHODS: The feasibility of
      improving dose conformity by using variable source-to-tumor distances was tested
      on brain CT datasets with tumor contours representing solitary lesions and an
      example with two lesions. For the single tumor cases, different tumor volumes
      from 2 to 83 cc were explored, while an example double lesion had a total volume
      of 13 cc. Three different source-to-axis distances (SADs), 100, 80 and 65 cm,
      were used to create separate 5-field IMRT plans with the same beam angles for all
      SADs. For each example, the PTV dose coverage and critical organ doses were
      constrained to be the same, except for the normal brain doses that were
      determined by the dose conformity. High dose spillage outside the PTV was
      quantified by R50 (the ratio between the 50% isodose volume and the PTV), and the
      V12 (volume of normal brain receiving 12Gy or higher). RESULTS: R50 decreased
      monotonically with shorter SAD for all examples. Compared with 100 cm SAD,
      average R50 reductions of 13% and 19% were observed with 80 and 65 cm SAD
      respectively. Improved conformity was more notable on smaller lesions and the
      multiple lesion case. V12 also decreases significantly with shorter SAD.
      CONCLUSIONS: Improvement in dose conformity can be achieved on existing LINACS by
      reducing the treatment distance for each IMRT field. Sharper beam penumbra and
      smaller projected MLC leaf width contribute to the improvement. Precise delivery
      of non- isocentric beams can be challenging on traditional LINACS, but the
      problem is much more manageable on machines with precise robotic gantry and couch
      capabilities.

PMID- 28517071
TI  - SU-E-T-607: Determining Critical Objectives and Importance Factors for Prostate
      IMRT Treatment Planning.
AB  - PURPOSE: To determine the optimization objectives that are most critical in
      prostate IMRT treatment planning, and to demonstrate that clinically acceptable
      treatments can be obtained using fewer optimization objectives with intelligently
      chosen importance factors. METHODS: We develop a novel optimization method that
      uses a historical prostate IMRT treatment as an input to quantify importance
      factors for a given set of objectives in the treatment planning problem. An
      initial treatment planning formulation with many candidate objectives is
      formulated. Then, given a historical treatment, importance factors for the
      objectives are determined via inverse optimization. We analyzed the results over
      several patients and identified the most critical optimization objectives in
      prostate IMRT treatment planning. We then designed a new treatment planning
      formulation with only the critical objectives, determined the importance factors
      via inverse optimization, and then compared the dose distribution to that of the
      original planning problem. The method was applied to a homogeneous cohort of 12
      patients from Princess Margaret Hospital. RESULTS: A treatment plan generated
      using 18 objectives was replicated using only six objectives and inversely
      optimized importance factors. For the bladder and rectum, a combination of the
      objective that minimizes the mean dose and the objective that penalizes dose
      above 50 Gy was determined to be most critical, while objectives that minimize
      the maximum dose were found to be critical for the femoral heads. The bladder and
      rectum objectives carried more than 95% of the importance factor over all
      objectives. CONCLUSIONS: By identifying critical objectives, our method has the
      potential to significantly enhance the computational efficiency of a treatment
      planning problem. A simplified treatment planning formulation with importance
      factors that are determined via inverse optimization reduces the need for an
      iterative, trial-and-error process in treatment planning.

PMID- 28517072
TI  - SU-E-T-578: Beam Energy Dependence and Intermediate-Low Dose Bath on Normal
      Tissue When Comparing VMAT with Conventional IMRT.
AB  - PURPOSE: To evaluate the impact of beam energy and intermediate-low dose bath on
      normal tissue when comparing volumetric modulated arc therapy (VMAT) with
      conventional IMRT. METHODS: A total of 10 prostate patients were randomly chosen
      for this study. The clinical IMRT plans were designed with 5 coplanar 10 MV
      photon beams. To investigate impacts of energies and delivery methods, we created
      2 additional IMRT plans with 6 and 15 MV photons and 3 VMAT plans with 6, 10, and
      15 MV photons in the Pinnacle treatment planning system. All plans were evaluated
      in terms of target coverage, clinical endpoints for organs-at-risks (OAR), and
      intermediate-low dose distributions to normal tissue, for which endpoints of
      V5Gy, V10Gy, V20Gy, V30Gy, V40Gy, and V50Gy were used. For this study, normal
      tissue was further divided into near region (5 cm thick concentric shell of
      normal tissue surrounding the target) and far region (concentric shell of normal
      tissue surrounding the near region and target). Longitudinally, the total normal
      tissue in calculation was limited to 10 cm from field edges. RESULTS: No
      significant differences were found among 6 types of treatment plans in terms of
      target coverage, OAR sparing, plan quality, intermediate-low doses to the near
      region, and integral dose to the total normal tissue (p > 0.05). VMAT deposited
      less intermediate doses of 30-50 Gy and more low doses of 5-10 Gy to the far
      region than IMRT. For example, mean average V40Gy and V10Gy were 51 and 2,967 cc
      for VMAT, and 140 and 2,618 cc for IMRT, respectively. CONCLUSIONS: VMAT and IMRT
      plans created with different photon energies are comparable for target coverage
      and OAR sparing. For prostate treatment, VMAT redistribute normal tissue doses
      from intermediate range into low dose range while keeping the similar the
      integral dose as IMRT.

PMID- 28517073
TI  - SU-E-T-589: There was No Dosimetric Benefit in Sparing Bone Marrow in the
      Radiotherapy of Whole Pelvic Lymph Node Applying 6MV X-Ray RapidArc Plans.
AB  - PURPOSE: To investigate the dosimetric difference in sparing bone marrow in the
      radiotherapy of whole pelvic node comparing 6MV and 15MV X-ray RaidArc plans.
      METHODS: Twelve patients who had undergone radical surgery for cervical cancer
      and with demonstrated multiple pelvic lymph node metastases were treated with
      radiotherapy were selected. All pelvic bone was delineated to define the bone
      marrow, and the pelvic bones consisted of the hip bone, the sacrum, the vertebral
      body near planning target volume (PTV), and the upper parts of femur. RapidArc
      plans applying 6MV and 15MV X-ray with one single whole arc (counter-clockwise
      from 179 degrees  to 181 degrees ) were generated for each patient, and named
      RapidArc-6MV and RapidArc-15MV. The prescription dose was
      2.0Gy/fractionx28fractions. The dosimetric differences were compared. RESULTS:
      There were no significant differences in conformity index(0.90+/-0.03 Vs 0.89+/
      0.04), homogeneity index(1.08+/-0.01 Vs 1.08+/-0.02) and external volume
      index(0.08+/-0.04 Vs0. 09+/-0.05) between RapidArc-6MV and RapidArc-15MV(P>0.05).
      Neither there were no significant differences in V5 (93.6+/-6.4Vs92.2+/-7.3),
      V10(88.6+/-9.3Vs88.3+/-9.2), V20(76.9+/-12.6Vs76.9+/-11.2), V30 (57.9+/-
      10.5Vs55.9+/-11.5), V40(35.2+/-10.2Vs34.9+/-10.9) between RapidArc-6MV and
      RapidArc-15MV (P>0.05). The monitor untie of RapidArc-6MV (552+/-40Mu) was more
      than RapidArc-15MV (455+/-44 Mu) with significant difference (P<0.05).
      CONCLUSIONS: Compared to 15MV X-ray RapidArc plans, there was no dosimetric
      benefit in sparing bone marrow in the radiotherapy of whole pelvic lymph node
      applying 6MV X-ray.

PMID- 28517074
TI  - SU-E-T-560: Inter- and Intra-Fraction Variations in Esophageal Dose for Lung
      Cancer Patients, and the Impact of Setup Technique and Treatment Modality.
AB  - PURPOSE: To understand the dose-response of the esophagus in photon and proton
      therapy, it is important to appreciate the variations in delivered dose caused by
      inter- and intra-fraction motion. METHODS: Four lung cancer patients were
      identified who had experienced grade 3 esophagitis during their treatment, and
      for whom their esophagus was close, but not encompassed by, the treatment volume.
      Each patient had been treated with proton therapy using 35-37 2Gy fractions, and
      had received weekly 4DCT imaging. IMRT plans were also created using the same
      treatment planning constraints. In-house image registration software was used to
      deform the esophagus contour from the treatment plan to each phase of the 4DCT
      for each weekly image set. Daily setup using both bony and soft tissue (GTV)
      registration was simulated, and the treatment dose calculated for each CT image.
      Changes to the esophagus DVH relative to the treatment plan were quantified in
      terms of the relative volume of the esophagus receiving 45, 55, and 65Gy (V45,
      V55 and V65). RESULTS: For all combinations of treatment modality (photon,
      proton) and setup method (bony, GTV), intra-fraction motion resulted in a range
      of V45, V55 and V65 from 3.6 to 5.5%. Inter-fraction motion comparing daily
      exhale or inhale phases showed the range of V45, V55 and V65 from 8.5 to 18.6%
      (exhale) and 9.8 to 16.3% (inhale). CONCLUSIONS: Inter-fractional motion resulted
      in larger variations in dose delivered to the esophagus than intra-fractional
      motion. The inter-fraction range for V45, V55 and V65 varied by around 10%
      between patients. The treatment modality (photon, proton) and setup technique
      (bony, GTV) had minimal impact on the results.

PMID- 28517076
TI  - SU-E-T-614: Dose-Reactive Methods in Adaptive Robust Radiation Therapy for Lung
      Cancer.
AB  - PURPOSE: To perform adaptive radiation therapy treatments for lung cancer using
      IMRT; to show that adjusting the target dose after each fraction, in order
      to'react' to errors in the dose delivered in prior fractions, can lead to
      significant changes in the daily tumor dose over the treatment. METHOD AND
      MATERIALS: Before the start of treatment, the beamlet intensities are optimized
      to deliver the current target dose distribution for a target set of breathing
      patterns at minimal healthy tissue dose. In each fraction, the current beamlet
      intensities are delivered, and the patient's breathing pattern is measured. The
      breathing pattern set is updated using the breathing pattern, and the target dose
      distribution is updated to account for dose errors realized in the previous
      fraction. The beamlet intensities are then re-optimized for the updated dose
      distribution and uncertainty set, to be used in the next fraction. This process
      continues until the end of the treatment. We consider three types of updates to
      the target dose distribution: the reactive+/- update, which responds to both
      under and overdose; the reactive- update, which responds only to underdose; and
      the reactive+ update, which responds only to overdose. RESULTS: On breathing
      pattern sequences obtained from real patients, dose-reactive methods result in
      final dose performance comparable to non-dose-reactive methods. However, as the
      treatment progresses, the reactive+/- update results in growing daily underdose
      and overdose, the reactive- update results in growing daily overdose, and the
      reactive+ update results in growing daily underdose. In contrast, non-reactive
      methods have stable or decreasing tumor underdose and overdose. CONCLUSIONS: By
      incorporating dose-reaction, the final tumor dose distribution can be made to
      conform closely to the target dose distribution, but at the cost of increasing
      tumor underdose and/or overdose. This increasing heterogeneity may have
      implications for the biological effectiveness of treatments obtained by dose
      reaction.

PMID- 28517075
TI  - SU-E-T-600: Utilizing Collimator Rotation to Increase Maximum Treatable Target
      Dimensions Using an Elekta Synergy-S with Beam Modulator Multileaf Collimator.
AB  - PURPOSE: To determine if a rotated collimator on an Elekta Synergy-S with Beam
      Modulator MLC (BMx) allows for dosimetrically acceptable treatment of targets
      exceeding the length of the maximum field size (21*16cm). The BMx is a high
      resolution MLC with 4mm leaves but is of limited clinical use on patient target
      volumes exceeding 20cm in length. Rotation of the collimator utilizes the
      Pythagorean geometry to extend treatment length. This potentially increases the
      length of the PTV that be conformally treated. METHODS: Rods of 21-23cm length
      were contoured in water with the Pinnacle treatment planning system. The width of
      the rods varies from 1 -5cm. Four isocentric treatment plans were generated for
      each target: four-field conformal, 7-field IMRT, single-arc VMAT, and a modified
      double-arc VMAT (MDAV), with the collimator angled at 55 degrees . The MDAV
      method consists of two opposing 180 degrees  arcs with the collimator turned 55
      degrees  in opposite directions. A successful plan is defined as 99% of the
      target volume being covered by a minimum of 95% of the prescribed dose.
      Conformality is determined as a ratio of the volume exposed to prescribed isodose
      and target volume. RESULTS: Targets of length 21cm, 22cm, and 23 cm are able to
      be treated with widths of 4cm, 5 cm, and 4cm respectively. The MDAV method
      achieves these results on all trials. The VMAT method achieves these results for
      the 21cm and 23cm long target. The IMRT Method achieves these results for the
      21cm long target. With the exception of the 1cm wide targets, the average
      conformality is approximately 2.5. CONCLUSIONS: Changing the collimator angle of
      the BMx Elekta-S machine allows for a 3cm length increase of targets up to 5cm.
      Further work will assess clinical suitability of these findings for treatment of
      head and neck tumors and spinal masses.

PMID- 28517077
TI  - SU-E-T-591: Volumetric-Modulated Arc Radiotherapy for Carcinomas of the Pituitary
      Adenomas: A Treatment Planning Comparison with Fixed Field IMRT.
AB  - PURPOSE: A treatment planning study was performed to compare volumetric-modulated
      arc radiotherapy against conventional fixed field IMRT on pituitary adenomas
      cancer patients. METHODS: CT datasets of 10 patients affected by carcinoma of the
      pituitary adenomas were included and four plans were generated for each case:
      fixed five-Fields and seven-Fields IMRT, single (RA1)- and double (RA2)-modulated
      arcs with the RapidArc technique. The radiation dose was prescribed as 45 Gy in
      25 fractions. DVHs were adopted for the statistics of above parameters, as well
      as conformal index (CI), homogeneity index (HI), dose-volumetric parameters of
      normal tissues, total accelerator output MUs and total treatment time. RESULTS:
      Target coverage resulted basically equivalent among four plans. CI and HI were
      0.84+/-0.04, 0.84+/-0.03, 0.86+/-0.03, 0.85+/-0.04 and 9.03+/-1.05 8.39+/-1.55,
      10.02+/-1.30, 10.59+/-1.30, respectively. The V20Gy (in %) and V40Gy (in %) of
      brainstem were 30.48+/-16.84, 10.23+/-7.47, 21.34 +/-12.2, 26.4+/-12.1 and 5.06+/
      4.37, 4.27+/-4.49, 3.97+/-4.45, 4.49+/-4.56, repectively. The max dose(Gy)of
      Optic nerve-right and Optic nerve-left were 31.87+/-12.04, 33.23+/-12.65, 28.96
      +/-13.42, 28.68+/-12.63 and 33.15+/-12.51, 34.15+/-11.51, 30.37 +/-12.41,30.09+/
      11.34 .Concerning the healthy brain tissue: V20Gy (in %) was 7.11 +/- 2.1,7.92 +/
      2.7, 8.12 +/- 1.8 and 8.0 +/- 2.0, respectively. The number of computed
      MU/fraction were 580 +/- 69 (5-IMRT), 598 +/- 112 (7- IMRT),474 +/-43(RA1), and
      477 +/- 77 (RA2) . CONCLUSIONS: In our study, rapidarc showed improvement in
      organ at risk sparing with uncompromised target coverage .Rapidarc could lead to
      the less MU and shortor delivery time compared to IMRT.

PMID- 28517078
TI  - SU-E-T-562: Reducing the Arc Span for CSA VMAT Delivery.
AB  - PURPOSE: To dosimetrically evaluate advantages and disadvantages of using
      multiple, shorter, sub-arcs versus full arc deliveries for treatment of cranio
      spinal axis (CSA) irradiation. METHODS: Five (n=5) cranio-spinal axis irradiation
      patients were planned using 2 complete arcs, one superior and one inferior; with
      gantry rotations from 1 to 359 degrees. Due to supine patient setup, each
      original full arc was then replanned split into two sub arcs with gantry
      rotations from 1 to 100 and 260 to 359 degrees creating 4 smaller arcs. The PTV
      was normalized such that 95% received at least 23.4 Gy in 13 fractions. The PTV
      was evaluated based on conformity number and homogeneity index. The normal
      structures were evaluated based on maximum and mean doses. Beam on times and
      monitor units were compared. RESULTS: Averaged over all patients, conformity
      number was calculated to be approximately 0.86 and 0.82 for full arc and sub arc
      plans respectively. The homogeneity index was approximately 1.07 and 1.06 for
      full arc and sub arc plans. This indicates better target conformity but less
      homogeneous dose distribution for full arc plans as compared with sub arc plans.
      With the exception of the eyes, each normal structure evaluated had lower maximum
      doses with subarc plans. All normal structures, with the exception of the left
      kidney, had lower mean doses using sub arc deliveries. Beam on times were shorter
      on average for full arcs, but the monitor units were lower on average for sub
      arcs. CONCLUSIONS: Overall, CSA patients would benefit from the use of sub arc
      treatment deliveries versus full arc deliveries. Nearly all normal structure
      doses were lower for sub arcs, while the PTV was still adequately covered and
      beam on times and monitor units were similar.

PMID- 28517079
TI  - SU-E-T-602: Comparison of Treatment Techniques for Pelvic Node Irradiation:
      Intensity-Modulated Photons versus Protons.
AB  - PURPOSE: Radiotherapy planning for iliac pelvic nodes can be challenging due to
      the close proximity of sensitive healthy tissues such as the bowel and rectum.
      Modern treatment techniques like photon intensity-modulated radiotherapy (IMRT)
      and intensity-modulated proton therapy (IMPT) offer improved healthy tissue
      sparing for similar target coverage. In this study we compare IMRT and IMPT plans
      for six post-cystectomy patients. METHODS: A dose of 50.4 Gy was prescribed to
      the planning target volume (PTV), which for IMRT is the clinical target volume
      (CTV) plus a 5 mm expansion for geometric uncertainties due to CTV and patient
      positioning errors, and for proton beams is the CTV plus the lateral 5 mm margin
      plus an additional longitudinal margin to allow for the proton range uncertainty.
      The optimization objectives are: 98% of the PTV receive at least 95% of the
      prescription, target maximum dose = 107% of prescription, rectum V[40Gy] < 30%
      and max = 105%, and bowel V[45Gy] < 125 cc and max = 107%. All IMRT and IMPT
      plans are made to achieve the target coverage objective. RESULTS: Using IMPT, the
      rectum would receive a mean dose of 9.0 Gy with an average (over the six
      patients) maximum dose of 38.1 Gy. Using IMRT, the rectum would receive a mean
      dose of 13.0 Gy and an average maximum dose of 37.6 Gy. The IMPT plans give a
      mean dose of 17.9 Gy and a maximum dose of 53.4 Gy for the bowel, whereas the
      IMRT plans give a mean dose of 23.8 Gy and a maximum dose of 53.2 Gy. Both the
      rectum and bowel show slightly lower mean doses for IMPT. CONCLUSIONS: Our
      results indicate that IMPT plans improve normal tissue sparing as compared to
      IMRT plans and provide adequate dose coverage of the target volume.

PMID- 28517080
TI  - SU-E-T-573: Quality and Deliverability of Intensity Modulated Neutron
      Radiotherapy (IMNRT) Plans.
AB  - PURPOSE: Intensity Modulated Neutron Radiotherapy (IMNRT) has been commissioned
      for clinical use. The number of allowable segments in IMNRT plans is limited by
      MLC speed. Quality and deliverability of static IMNRT treatment plans using the
      TG-119 test suite were evaluated to establish guidelines for the number of
      segments per plan. METHODS: Treatment plans were created and optimized to
      specified constraints for all cases in the TG-119 test suite using the Varian
      Eclipse TPS. A 4MV photon beam with similar penetration characteristics as the
      fast neutron beam was used as a surrogate for this optimization. Final dose
      calculations were performed using an in-house TPS commissioned for neutron dose
      calculations. Following optimization, MLC segments were created for three ranges
      of total plan complexity - very limited (15-23 segments), limited (24- 31
      segments), and unlimited. Calculated DVHs were then compared for compliance with
      TG-119 dose constraints. The estimated time of delivery for plans in each range
      was calculated based on known delivery parameters. RESULTS: The prostate case
      passes all constraints for each complexity level. All other plans fail to meet at
      least one constraint for one or more of the complexity levels. For all cases
      combined, the very limited, limited, and unlimited complexity levels meet 16, 17,
      and 19 of 23 total dose constraints, respectively. The mean estimated delivery
      time for the very limited, limited, and unlimited plans is 34 minutes (range: 27
      39), 40 minutes (range: 34-45), and 68 minutes (range: 53-81) respectively,
      neglecting any delay due to therapists entering the treatment room. CONCLUSION:
      IMNRT plan quality is limited by current MLC capabilities. IMNRT plans should be
      limited to 25 segments to ensure a reasonable treatment time of 45 minutes. Even
      with this small number of segments, we were able to meet most dose constraints
      set forth in TG-119.

PMID- 28517082
TI  - SU-E-T-595: Comparison of Volumetric Modulated Arc Therapy (VMAT) and Static
      Intensity Modulated Radiotherapy (IMRT) for Malignant Pleural Mesothelioma in
      Patients with Intact Lungs/Post Pleurectomy.
AB  - PURPOSE: This planning study compares VMAT and static gantry, sliding window IMRT
      for malignant pleural mesothelioma for post pleurectomy. METHODS: We compared
      plans for a left sided (L) and a right sided case (R). Plans used clinically
      approved planning target volumes (PTVs) and critical organ contours. IMRT plans
      employed 7-8 6 MV photon beam directions over a 215 degrees  range centered on
      the ipsilateral lung. VMAT plans used 4 partial arcs within the same range and
      energy. Prescription dose per fraction was 1.8 Gy; case L went to 50.4 Gy, case R
      to 46.8 Gy. Planning objectives were: Lyman model NTCP for both lungs < 25%;
      contralateral lung, mean dose < 8 Gy; heart, V30 Gy < 50%, mean < 30 Gy; Each
      Kidney, V18 Gy < 33%; liver_not_GTV, mean < 30 Gy, V30 Gy < 50%; stomach not PTV,
      mean < 30 Gy; cord maximum < 45 Gy; bowel maximum < 55 Gy, D05 < 45 Gy; PTV D95 =
      94%, V95 = 94%, D05 = 115%. Dose calculation was done with the AAA algorithm.
      RESULTS: VMAT and IMRT both met the dosimetric constraints. The VMAT MU were 887
      (L)_and 896 (R) and for IMRT were 1691 (L) and 2409 (R). IMRT required 14-16
      fields (wide-field splitting). The delivery times were 8 minutes (VMAT) and 20
      minutes (IMRT). For coverage and plan homogeneity parameters within 1.5% - 2%,
      VMAT better spared organs at risk. CONCLUSIONS: Both VMAT and IMRT are feasible
      techniques for the treatment of malignant pleural mesothelioma with intact lungs,
      with less MU and a shorter delivery time for VMAT. Additional cases must be
      planned to test generality of our preliminary results.

PMID- 28517081
TI  - SU-E-T-584: Dosimetric Comparison Between Static IMRT and VMAT for a Four- Lesion
      Brain Treatment.
AB  - PURPOSE: Sparing brain volume is the goal when designing plans for multiple brain
      tumors. We compared dose distributions for tumor and normal tissues using VAMT
      and static IMRT. METHODS: A patient presented with recurrent meningioma with 4
      lesions identified. The greatest dimensions for the tumors were 0.4 to 2.0 cm.
      The tumor sizes and locations can be treated with a single plan with 1.8
      Gy/fraction, 30 fractions. A 6-field non-coplanar IMRT with the gantry(G) and
      couch(C) in IEC scale were used: G0C0, G45C0, G330C0, G240C0, G50C90, and
      G120C90. IMRT was performed using iPlan sliding-window. For VMAT, four arcs were
      used; two using 350 degree from G175 to G185 and the other two using 175 degree
      from G0 to G175. Two arcs were designed with couch=0 and the rest two using
      couch=90 degree. VMAT was designed with Eclipse system. Tumors and normal brain
      were contoured in the iPlan and then exported to Eclipse to maintain identical
      volume. DVH for normal brain was compared for the same tumor coverage from the
      two plans. RESULTS: Either static IMRT or VMAT generated an acceptable coverage
      for these four tumors. The conformity of tumor coverage was better in VMAT than
      that using IMRT; the range of min.-max. doses were: 57.5-63.5 Gy from VMAT vs.
      54.1-64.9 Gy from IMRT. For normal brain, DVH did not show a clear difference
      between the two plans. For doses 5-15 Gy, VMAT delivered 1- 10% more brain volume
      (1040 cc) but 1-2 % less volume in 30-40 Gy than that from static IMRT.
      CONCLUSIONS: Either static IMRT or VMAT can adequately be used to treat multiple
      lesions with a single isocenteric treatment. VMAT plan demonstrated improved
      tumor coverage, spared 1- 2% brain tissue at 30-40 Gy but irradiated up to 10%
      more brain in 2-7 Gy. The patient was treated with VMAT.

PMID- 28517083
TI  - SU-E-T-566: A Dosimetric Comparison of Partial Breast Irradiation Technique
      Depending on the Tumor Locations in Patient's Breast.
AB  - PURPOSE: The present study was designed to suggest the optimal treatment
      modalities among 3D-conformal radiation therapy, electron beam therapy and
      helical-tomotherapy depending on classified tumor locations in patient's breast
      using Partial Breast Irradiation (PBI) technique. METHODS: The CT dataset of six
      patients who had received lumpectomy treatments was used to treatment plans of 3D
      conformal radiation therapy, electron beam therapy and helical-tomotherapy. The
      tumor locations were classified into eight sections according to the quadrants of
      the breast and to the superficial or deep positions. To evaluate the dosimetric
      results from the suggested treatment modalities and tumor locations, conformation
      number, radical dose-homogeneity and delivered doses to normal tissue were
      calculated. Kruskall-Wallis, Mann-Whitney U and Bonferroni method was used as
      statistical analysis. RESULTS: Helical-tomotherapy is not recommendable method in
      PBI technique because the dosimetric results from radical dose- homogeneity and
      the delivered dose to organ at risk showed worse results at all tumor locations
      compared to other modalities. For helical-tomotherapy, the volume of heart
      received more than 2.5 Gy was maximized more than 90% of total heart volume at
      all tumor locations. Electron beam therapy showed good sparing effect to normal
      tissues and acceptable target coverage in Lower Inner Quadrant-Superficial (LIQ
      S) and Lower Inner Quadrant- Deep (LIQ-D) cases. CONCLUSIONS: Electron beam
      therapy could be recommendable method to treat tumor at LIQ-S, LIQ-D locations
      rather than 3D-conformal radiation therapy, helical-tomotherapy at PBI technique
      because electron beam therapy is considered to provide the acceptable target
      coverage and the greatly lower dose to surrounding tissue.

PMID- 28517084
TI  - SU-E-T-606: Optimal Emission Angle Selection in Rotating Shield Brachytherapy.
AB  - PURPOSE: In this work a general method is presented that enables clinicians to
      rapidly select Rotating shield brachytherapy (RSBT) emission angles based on the
      patient-specific tradeoff between delivery time and tumor dose conformity.
      Cervical cancer cases are used as examples. METHODS: Anchor plans with high dose
      conformity but infeasible delivery times are generated with a fine emission
      angle, with simulated annealing. The RSBT emission angle selector determines the
      optimal emission angle for each case by efficiently solving a globally-optimal
      quadratic programming problem that closely reproduces the angular distribution of
      beam intensities from the anchor plan. Pareto plots of the dosimetric plan
      quality metrics, such as D90 versus the delivery time, are generated for
      clinicians. In this work two cervical cancer cases were considered for
      verification. The RSBT system was assumed to be a Xoft AxxentTM electronic
      BT(eBT) source with a 0.2mm tungsten shield. The intent for each treatment plans
      was to maximize tumor D90 while respective the GEC-ESTRO recommended constraints
      on the D2cc values to OARs. RESULTS: Generating anchor plans with simulated
      annealing takes 10-20min while emission angle selection can finish within
      seconds. The shield sequencing algorithm also ensures the balance between D90 and
      delivery time. One case shows that the D90 can achieve 98.3Gy10 with emission
      angle 202.5 degree with 8.64min delivery, while the conventional intracavitary
      plan has D90 65Gy10 with 2.86min delivery. Another case shows RSBT with emission
      angle 67.5 degree can produce D90 108.7Gy10 with 44min, and the conventional plan
      uses 2.2min for D90 48.9Gy10. CONCLUSIONS: The RSBT emission angle selection
      algorithm enables the users to rapidly determine the best emission angle for a
      given cervical cancer case by selecting the most appropriate D90 and delivery
      time. RSBT may be a less invasive alternative to intracavitary and supplementary
      interstitial BT for the treatment of cervical cancer tumors, supported in part by
      NSF grants CCF-0830402 and CCF-0844765, the NIH grant K25-CA123112.

PMID- 28517085
TI  - SU-E-T-577: Dosimetric Comparison of Volumetric Modulated Arc Therapy (VMAT),
      Step and Shoot and Sliding Window IMRT for Prostate Cancer.
AB  - PURPOSE: This study aims to evaluate treatment plans generated by Step- and-Shoot
      (SS), Sliding Window (SW) and Volumetric Modulated Arc Therapy (VMAT) in order to
      assess the differences in dose volume histograms of planning target volume (PTV)
      and organs at risk (OAR), conformity indices, radiobiological evaluations, and
      plan quality for prostate cancer cases. METHODS: Six prostate cancer patients
      treated in our center were selected for this retrospective study. Treatment plans
      were generated with Eclipse version 8.9 using 10 MV photon beams. For VMAT,
      Varian Rapid Arc with 1 or 2 arcs, and for SS and SW IMRT, 7-9 fields were used.
      Each plan had three PTVs with prescription doses of 81, 59.4, and 45 Gy to
      prostate, to prostate and lymph nodes, and to pelvis, respectively. Doses to PTV
      and OAR and the conformal indices (COIN) were compared among three techniques.
      The equivalent uniform dose (EUD), tumor control probability (TCP) and normal
      tissue complication probability (NTCP) was also calculated and compared. RESULTS:
      The mean doses to the PTV prostate on average were 83 Gy and the percent
      differences of mean dose among all techniques were below 0.28. For bladder and
      rectum, the percent differences of mean dose among all techniques were below 2.2.
      The COIN did not favour any particular delivery method over the other. The TCP
      was higher with SS and SW for four patients and higher with VMAT for two
      patients. The NTCP for the rectum was the lowest with VMAT in all patients except
      one. CONCLUSIONS: Preliminary data shows similar target coverage in general. We
      will extend our study to include 15 patients to compare different approaches with
      statistics. We will attempt to define characteristics predictive of the superior
      delivery technique.

PMID- 28517086
TI  - SU-E-T-588: A Treatment Planning Comparison of Dual-Arc VMAT Vs. Helical
      Tomotherapy for Post-Mastectomy Radiotherapy.
AB  - PURPOSE: To investigate the feasibility of volumetric modulated arc therapy
      (VMAT) for post-mastectomy radiotherapy (PMRT) and to compare dual- arc VMAT
      treatment plans to helical tomotherapy (HT) plans on the basis of dosimetric
      quality, radiobiological calculations and delivery efficiency. METHODS: Dual-arc
      VMAT and HT treatment plans were created for fifteen patients previously treated
      at our clinic. Planning target volumes (PTV) included the chest wall (CW) and
      regional lymph nodes. The following metrics were used to compare treatment plans
      for each patient: dose homogeneity index (DHI) and conformity index (CI);
      coverage of the PTV; dose to organs at risk (OAR); tumor control probability
      (TCP), normal tissue complication probability (NTCP) and secondary cancer
      complication probability (SCCP); and treatment delivery time. Differences between
      treatment plans were tested for significance using the paired Student's t-test.
      RESULTS: Both modalities produced clinically acceptable PMRT plans. VMAT plans
      showed better CI (p < 0.01), and better OAR sparing at low doses than HT plans.
      For example, VMAT plans showed a 26% (p < 0.01) and 9% (p < 0.01) decrease in
      V5Gy in the lungs and heart respectively. On the other hand, HT plans showed
      better DHI (p < 0.01) and PTV coverage (p < 0.01). HT plans also showed slightly
      better OAR sparing at higher doses, including 8% (p < 0.01) and 9% (p < 0.01)
      lower maximum doses to the lungs and heart, respectively. Both modalities
      achieved nearly 100% tumor control and approximately 1% NTCP in the lungs and
      heart, with VMAT showing lower SCCP (p < 0.01). VMAT plans also required 66.2%
      less time to deliver. CONCLUSIONS: Both VMAT and HT are suitable treatment
      options for PMRT. Our study showed that VMAT"'in addition to being significantly
      faster'"achieved better CI and low dose OAR sparing while HT achieved better DHI.
      This work was supported in part by a research support from Elekta, Ltd. However,
      Elekta, Ltd., did not participate in the study design; in the collection,
      analysis, and interpretation of data; in the writing of the manuscript; or in the
      decision to submit.

PMID- 28517087
TI  - SU-E-T-559: Evaluation of Flatening Filter Free (FFF) Beams in Radiotherapy of
      Head and Neck Cancer.
AB  - PURPOSE: To investigate th applicability of the flattening filter free (FFF) to
      fractionated radiotherapy of head and neck cancer. METHODS: Twelve patients
      previously treated with IMRT were selected. A SIB protocol was chosen so that
      66/54 Gy were prescribed to the gross tumors/elective nodal volumes in 30
      fractions. Photon beams of 6X(6X-FFF) were used for both IMRT (@ 9 gantry angles)
      and VMAT (single and dual full arcs). Consistent optimization and acceptance
      criteria were used for all plans, with prescription dose to cover 90% of PTV66
      and hot spots limited to 110% and within PTV66. Both plan quality and deliver
      ability were compared. RESULTS: All plans met clinical objectives. The IMRT plan
      quality is similar or slightly better than VMAT, except that PTV66 conformity
      index is significantly better in 2-arc VMAT (1.18) than IMRT (1.32). The total
      MUs for IMRT are 1680/2090 for 6X/6X-FFF, a 24% increase. However, the total beam
      on time (BOT) under treatment automation is 430/400 seconds for 6X(@300
      MU/min)/6X-FFF (@400 MU/min), a 6% decrease. Increasing dose rate to the maximum
      (600/1400 for 6X and 6X-FFF) can reduce BOT by up to 50%, but at a cost of
      increased MU (up to 40%) and degraded plan quality. Significant reduction in MU
      and BOT are realized in VMAT, with ~600 MU for both 6X and 6X-FFF and either
      single or dual-arcs. The BOT for VMAT is governed by the gantry speed and
      approximately 1 min for single arc and 2 min for dual arcs. CONCLUSIONS: Plan
      quality is similar between IMRT and 2-arc VMAT for both 6X and 6X-FFF. Total MU
      for IMRT and delivery time is significantly higher for IMRT than VMAT, but not
      much different between flat and non-flat beams. For standard fractionated
      radiotherapy of HN cancer, there is no advantage for the non-flat beam. The
      recommended choice is 2-arc VMAT.

PMID- 28517088
TI  - SU-E-T-599: Pelvic Volumetric Modulated Arc Therapy with Hypofractionated
      Concomitant Integrated Prostate Boost: An Isoeffective Dose Comparison.
AB  - PURPOSE: Pelvic irradiation is controversial in prostate cancer and has been
      associated with significant late toxicity, but may be beneficial in patients with
      high risk disease. To evaluate dose reduction to organs at risk (OAR), we
      compared volumetric intensity modulated arc therapy with hypofractionated
      concomitant integrated prostate boost (VMAT) to sequential 3-D conformal 4 field
      pelvis plan and prostate IMRT boost (Sequential IMRT). METHODS: The planning CT's
      of 20 consecutive high risk prostate cancer patients were utilized for this
      study. Dose planning using triple A algorithm (Varian Eclipse). CTV included
      prostate and proximal seminal vesicles. These were expanded by 6 mm for the PTV1
      . Pelvic LN were delineated and expanded by 3 mm for the PTV2. Volume based
      equivalent dose at 2Gy/fx (EQD2) doses were calculated using alpha/beta ratios of
      1.5 Gy for the prostate and 3 Gy for normal tissues. VMAT prescription was 73.6
      Gy (EQD2-80 Gy) to PTV1 and 54.4 Gy to PTV2 (EQD2-50 Gy) in 32 fractions of 2.3
      Gy and 1.7 Gy, respectively. Sequential prescription was 46 Gy to the pelvis and
      34 Gy for IMRT boost to a total of 80 Gy in 40 fractions of 2 Gy each. RESULTS: A
      significant reduction in mean dose was observed for rectum, bladder, bowel, femur
      head, and penile bulb for VMAT vs. Sequential IMRT (p<0.001) (table 1). Rectal
      V75 and V70 was 6.2% and 11.2% for VMAT and 13.6% and 19% for Sequential IMRT
      (p<0.001). Bowel V50 was 0.35 cm3 vs. 24.1 cm3 (p<0.001), respectively. The 98%
      isodose conformity index for the PTV was 1.44 for VMAT vs. 1.69 for Sequential
      IMRT (p<0.001). CONCLUSIONS: VMAT with concomitant boost significantly reduced
      dose to OAR compared to Sequential IMRT, potentially leading to less late
      toxicity, while providing excellent target coverage and conformity. Furthermore,
      reduction of treatment planning time and both individual fraction and overall
      treatment delivery time inherent in this approach, offer significant advantages
      for both providers and patients.

PMID- 28517089
TI  - SU-E-T-570: Improvement to the Histogram Analysis in Radiation Therapy (HART): An
      Open Source Software System for the Multi-Dimensional Dose- Volume Histogram
      Analysis in Digital Image Communication in Medicine - Radiation Therapy (DICOM
      RT) Treatment Plans.
AB  - PURPOSE: Histogram Analysis in Radiation Therapy (HART) is an efficient and
      accurate dose-volume histogram (DVH) computational tool in radiotherapy research.
      Several applications of the program have been presented previously (J Appl Clin
      Med Phys 11(1): 3013, 2010; Med Phys 38(6), p.3678, 2011) for the Radiation
      Therapy Oncology Group (RTOG) users. The program has been further developed to
      incorporate various types of DVH analysis features to support the research using
      DICOM-RT plans. The main objective of this work was to present the improvement
      and compatibility of the program for the DICOM-RT plans. METHODS AND MATERIALS:
      MATLAB based codes were primarily designed to read and write a simpler HART
      format from the standard DICOM-RT data objects exported from the Xio treatment
      planning system (CMS Inc., St. Louis, MO). This format employed an optimal
      polynomial fitting technique to interpolate the co-ordinates of the contours in
      the regions-of-interest. The format was efficient for the (a) precise extraction
      of the cumulative DVH (cDVH) and spatial DVH (sDVH; x-,y-, and z-DVHs
      respectively) data- statistics, (b) universal-plan indices evaluation, (c)
      biological modeling based outcome analyses (BMOA), (d) radiobiological dose
      response modeling, and (e) physical parameterization modules. The fundamental DVH
      statistics were validated using the DVH statistics extracted from the
      Computational Environment for Radiotherapy Research program. RESULTS: HART offers
      various types of DVH computational functionalities, several plan evaluation and
      radiobiological outcome analysis modules in a user- friendly software package for
      the RTOG and DICOM-RT planners. The cDVH and BMOA modules were found to be the
      most applicable features for the global researchers. CONCLUSIONS: HART is a novel
      and universal multi-dimensional DVH analysis tool for the radiation therapy
      research. We further expect to develop HART for the space-time DVH analysis and
      proton therapy applications. The software is available online
      (http://www2.uic.edu/~apyaku1) for the radiotherapy research. This work was
      partially supported by NIH-NIDCD grant.

PMID- 28517090
TI  - SU-E-T-610: Impact of Variable Beam Spot Size on Treatment Time in Particle
      Therapy.
AB  - PURPOSE: The dosimetric advantage of particle therapy comes with a much higher
      infrastructure investment and operation costs. Increasing patient throughput is a
      key factor to manage operation costs. We investigate the impact of variable beam
      spot sizes on treatment time and discuss the tradeoffs involved. METHODS: The
      following realistic assumptions were used. (1) The beam traveling speed is
      independent of the beam spot size. (2) The beam spot is a 2D Gaussian. Changing
      the beam spot size implies varying the standard deviation. (3) The maximum beam
      intensity is a constant independent of the beam spot size. Increasing the beam
      spot reduces the fluence. (4) Varying the beam spot size incurs in a reset time
      penalty.A 2D tumor was used in the study. Dose calculations were based on pencil
      beam kernels from GEANT4.The total treatment time is divided into the beam travel
      time, the beam-on time, andthe time for changing the spot size. RESULTS: We found
      that: (1) Changing the beam spot size has no impact on the beam-on time, because
      the maximum beam intensity is independentof the beam spot and increasing the beam
      spot only reduces the fluence. (2) Larger beam spot size shortens the total
      travel time inversely proportional to the radius of the beam spot. (3) Plans with
      different beam spot sizes have similar dosimetric qualities. (4) If higher beam
      intensity could be used for larger beam spot size, savings in beam-on time would
      be inversely proportional to the intensity available. CONCLUSIONS: We have
      studied the interplay among beam intensity, travel time, and beam size reset time
      for a scanning beam with variable beam spot size. Our initial studies show
      necessary conditions for and limitations on savings in total treatment times.
      Further studies are being carried out to find additional time saving sources.
      Supported in part by NSF CBET-0853157.

PMID- 28517091
TI  - SU-E-T-613: Improving Dose-Shaping and OAR-Sparing Using Robust Statistical
      Methods.
AB  - PURPOSE: To achieve a better balance between tumor coverage and organ-at-risk
      (OAR) sparing by applying robust statistical methods to IMRT inverse
      optimization. METHODS: We propose a novel approach to shape dose dropoff from the
      PTV by minimizing the L1 norm of the difference between the obtained and aimed
      dose value and the total variation of the dose distribution on the PTV and OAR
      regions. Minimizing the L1 norm results in operand values that are mostly small
      but potentially large on a sparse set. Applying this structure to both dose
      discrepancy and dose gradient, our method achieves: 1) sparsely-distributed, high
      dose gradients; 2) structure dose-homogeneity; and 3) connectivity in the
      distribution of high-gradient voxels on the PTV's surface. Dose-volume histograms
      (DVHs) and visual observations of dose maps were compared among two plans
      optimized for the same dynamic IMRT prostate case: 1) the clinical plan (plan_c);
      and 2) a plan optimized using the TV energy, L-1 norm, and an over-dose quadratic
      (plan_r). Importance factors for the objective function of planr were chosen
      empirically. The beam geometry was obtained from the clinical plan, and the
      solution was optimized with linear programming. RESULTS: Plan_r improved dose
      conformity, increased overall bladder-sparing, and globally increased rectum
      sparing relative to plan_c. CONCLUSIONS: These results suggest that robust
      formulations may be used to improve dose-shaping and OAR-sparing. The numerical
      stability and implementation simplicity of our method permits fast translation to
      the clinic.

PMID- 28517092
TI  - SU-E-T-561: A Comparative Study of Single Verses Two Field Daily Fraction for
      Treatment of Prostate Cancer Using IMPT, Double-Scattered, and SUFD Delivery
      Technique.
AB  - PURPOSE: We conducted an investigation to evaluate the robustness of different
      proton therapy delivery technique for treatment of prostate cancer. Three
      commonly used delivery techniques; intensity modulated, double-scattered, and
      single field uniform dose delivery was investigated for one field verses two
      field daily fraction. METHOD: Computer tomography (CT) for a patient was deformed
      based on acquired daily MVCTs obtained during the course of treatment by a
      Tomotherapy unit. The deformed CTs were used for proton planning
      retrorespectively using intensity modulated (IMPT), double-scattered (DSPT), and
      single field uniform dose (SFUD) delivery technique. The plans were evaluated for
      single-field versus two-field per fraction for each technique. The plans
      robustness was evaluated for each technique by comparing the maximum dose to
      rectum, bladder, prostate and CTV as well as the minimum dose to prostate and
      CTV. In addition, 95% coverage to prostate and CTV compared for each plan.
      RESULTS: The average and STD for deformed prostate volume was 22.4 +/-0.5 (1s)
      for the course of treatment. On average the maximum dose delivered to rectum and
      bladder with single-field verses two-field IMPT were higher by 2.5%. With same
      respect, the single-field verses two-field for DSPT were 0.5% higher for rectum
      but the same for bladder. Single-field SFUD delivered 1% higher dose to both
      rectum and bladder compare to two-field delivery. Table 1 summarizes the results.
      CONCLUSION: Single-field IMPT delivered higher dose to rectum, bladder, prostate,
      and CTV than any other technique. But two-file IMPT delivered most homogenous and
      consistent dose to prostate and CTV with much lower dose to rectum and bladder
      compare to DSPT and SFUD. With same respect two-field SFUD delivery produced
      better dose coverage to prostate and CTV compare to DSPT. The two-field IMPT with
      conjunction of daily cone beam CT can be considered a better dose delivery
      technique.

PMID- 28517093
TI  - SU-E-T-601: Dosimetric Evaluation of the Parameter Variation with Varying
      Calculation Grid Size in the IMRT Cases.
AB  - PURPOSE: The aim of this study is to compare the plan results that are obtained
      by using different calculation grid sizes ranging from 0.15 to 0.50 cm, and the
      same dose calculation algorithm (Superposition), in Intensity Modulated
      Radiotherapy (IMRT) for different treatment sites. Results are then used to study
      the suitability of dose grid size with respect to site. METHODS: For each of the
      calculation grid sizes, three different sites; namely, Lung, Prostate, and Head
      and Neck were analyzed. Treatment plans were created using 6MV photon beam
      quality and IMRT technique on the CMS XiO (Computerized Medical System, St.Louis,
      MO) treatment planning system. Dose volume histograms were generated for each of
      the cases and statistical analysis performed included mean relative difference
      and Homogeneity Index for target structures. Comparison was done first by using
      0.30 cm calculation grid as a golden standard and keeping the same number of
      monitor units (MUs) per beam for each grid size, then the second part involved
      renormalizing plans to have the same target coverage (100% of the prescription
      dose covering at least 95% of the target volume) for each grid size used. Future
      study plans include treatment plans delivery on Varian 21 EX linear accelerator
      with Millennium (120) MLC and their verification with the Sun Nuclear Mapcheck 2D
      array. To increase the diode array resolution, 2D array will be shifted in 1 mm
      increments in x and y direction. Measured fields will be merged using Sun Nuclear
      Files Combined function and compared with intensity maps exported from the CMS
      XiO treatment planning system calculated with minimum segment size of 1 cm.
      RESULTS: The maximum percentage of variation recorded between calculation grid
      sizes used was in the case of the Head and Neck treatments. For the lung and
      prostate cases there was little variation in the results based on the calculation
      grid size chosen, specifically between 0.30, 0.20 and 0.15 cm. However head and
      neck and prostate cases with nodal involvement showed significant variation in
      the dosimetric results based on the grid size chosen. Overall results vary from
      case to case and also depend on the plan complexity. For larger treatment areas
      calculating with the grid size smaller than 0.30 cm may be impossible as time
      needed for calculation rises exponentially with the field size involved.
      CONCLUSIONS: IMRT places a higher requirement on dose grid resolution than
      conventional radiation therapy. While 0.30-0.40 cm grid was assumed adequate for
      conformal treatment planning, smaller dose grid is required at least in the areas
      of high dose. In the cases where steep dose gradients exist smaller grid size
      should be used while calculating and evaluating treatment plans, as the choice of
      the calculation grid size may in certain cases even influence clinical results.

PMID- 28517094
TI  - SU-E-T-572: A Plan Quality Metric for Evaluating Knowledge-Based Treatment Plans.
AB  - PURPOSE: In prostate IMRT treatment planning, the variation in patient anatomy
      makes it difficult to estimate a priori the potentially achievable extent of dose
      reduction possible to the rectum and bladder. We developed a mutual information
      based framework to estimate the achievable plan quality for a new patient, prior
      to any treatment planning or optimization. METHODS: The knowledge-base consists
      of 250 retrospective prostate IMRT plans. Using these prior plans, twenty query
      cases were each matched with five cases from the database. We propose a simple
      DVH plan quality metric (PQ) based on the weighted-sum of the areas under the
      curve (AUC) of the PTV, rectum and bladder. We evaluate the plan quality of
      knowledge-based generated plans, and established a correlation between the plan
      quality and case similarity. RESULTS: The introduced plan quality metric
      correlates well (r2 = 0.8) with the mutual similarity between cases. A matched
      case with high anatomical similarity can be used to produce a new high quality
      plan. Not surprisingly, a poorly matched case with low degree of anatomical
      similarity tends to produce a low quality plan, since the adapted fluences from a
      dissimilar case cannot be modified sufficiently to yield acceptable PTV coverage.
      CONCLUSIONS: The plan quality metric is well-correlated to the degree of
      anatomical similarity between a new query case and matched cases. Further work
      will investigate how to apply this metric to further stratify and select cases
      for knowledge-based planning.

PMID- 28517095
TI  - SU-E-T-617: Towards Fully Automated Multi-Criterial Plan Generation: A
      Prospective Clinical Study.
AB  - PURPOSE: To prospectively compare plans generated with iCycle, an in-house
      developed algorithm for fully automated multi-criterial IMRT beam profile and
      beam orientation optimization (Breedveld, Med. Phys. 2012), and plans manually
      generated by dosimetrists with the clinical treatment planning system. METHODS:
      For 20 randomly selected head-and-neck cancer patients with various tumour
      locations (of whom 13 received sequential boost treatments) we offered the
      treating physician the choice between an automatically generated iCycle plan and
      a manually optimized plan following standard clinical procedures. While iCycle
      used a fixed'wish-list' with hard constraints and prioritised objectives, the
      dosimetrists manually selected the beam configuration and fine-tuned the
      constraints and objectives for each IMRT plan. Dosimetrists and treating
      physicians were not informed in advance whether a competing iCycle plan was made
      or not. The two plans were simultaneously presented to the physician who then
      selected the plan to be used for treatment. For the patient group, we quantified
      differences in PTV coverage and sparing of critical tissues. RESULTS: In 32/33
      plan comparisons the physician selected the iCycle plan for treatment. This
      highly consistent preference for automatically generated plans was mainly caused
      by improved sparing for the large majority of critical structures. With iCycle,
      the NTCPs for parotid and submandibular glands were reduced by 2.4% +/- 4.9%
      (maximum: 18.5%, p=0.001) and 6.5% +/- 8.3% (maximum: 27%, p=0.005),
      respectively. The reduction in mean oral cavity dose was 2.8 Gy +/- 2.8 Gy
      (maximum: 8.1 Gy, p=0.005). For swallowing muscles, esophagus and larynx, the
      mean dose reduction was 3.3 Gy +/- 1.1Gy (maximum: 9.2 Gy, p<0.001). Moreover,
      for 15 patients, the target coverage was improved as well. CONCLUSIONS: In 97% of
      cases, the automatically generated plan was selected for treatment because of
      superior quality. Apart from improved plan quality, automatic plan generation is
      economically attractive because of reduced workload.

PMID- 28517096
TI  - SU-E-T-583: Feasibility of Constraining Dose to the Nausea Center (area Postrema
      and Dorsal Vagal Complex) in IMRT Treatment Planning of the Head and Neck.
AB  - PURPOSE: Nausea and vomiting have been known to occur in patients undergoing
      external beam radiation treatments for head&neck cancers. We sought to determine
      the feasibility of limiting the dose delivered to the nausea center, area
      postrema (AP) and dorsal vagal complex (DVC), for these patients without
      compromising target coverage and critical organ doses. METHODS: In a
      retrospective study 23 oropharyngeal cancer patients were identified as being
      treated with definitive or adjuvant radiotherapy at Memorial Sloan Kettering
      Cancer Center. Patients were treated solely with external beam radiation using
      intensity modulated radiation therapy (IMRT). The nausea center was carefully
      contoured in the treatment CT with the assistance of a board certified
      neuroradiologist. The doses delivered to the nausea center were calculated for
      each plan delivered. Cases were replanned offline to determine the lowest
      achievable nausea center dose that does not compromise the overall PTV coverage
      or critical structures doses, these being brainstem, spinal cord, cochleas, and
      temporal lobes. RESULTS: Patients reporting higher nausea grade had median AP and
      DVC doses of 38.7Gy and 40.4Gy, respectively. Patients reporting higher vomiting
      grade had median AP and DVC doses of 39.5Gy and 44.7Gy, respectively. Replanning
      resulted in reduced dose to AP by an average of 18% and to the DVC by an average
      of 16% while maintaining adequate target coverage and doses to the critical
      organs the same or decreased by 1-4% . We aim to achieve a max dose of 36Gy to AP
      and 38Gy to DVC for these cases. CONCLUSIONS: It is feasible to limit the doses
      to the nausea center without compromising target coverage or critical organ
      limits for oropharyngeal cancer patients undergoing IMRT treatment. Clinical
      results indicating an association between radiation dose to the nausea center and
      development of nausea and/or vomiting can potentially be addressed by
      implementing this technique.

PMID- 28517097
TI  - SU-E-T-594: Dosimetric Evaluation of Different Treatment Techniques for Prostate
      Cancer.
AB  - PURPOSE: To evaluate the Volumetric Modulated Arc Therapy (VMAT, RapidArc) and
      IMRT plan quality for prostate deliveries conducted by two different treatment
      planning systems: Oncentra Masterplan (Nucletron inc.) and Eclipse (Varian inc.).
      METHODS: We investigated ten prostate treatment delivery plans. For a given case
      studied we created a RapidArc plan (Eclipse), a VMAT and an IMRT plan (Oncentra)
      by using both treatment planning systems. The rotational therapy plans consisted
      of 2 to 3 arcs and the IMRT fields consisted of 7 to 9 fields. The prescription
      dose was 200 cGy X 40 fx using a Varian Trilogy with 10 MV beams. The treatment
      parameters were used to evaluate the plan quality: the minimal, mean and maximal
      doses to the target (PTV) and the volumes received 65Gy and 40 Gy, respectively,
      for the rectum and bladder, V65 and V40. In addition, we calculated the
      conformity index (CI) and the heterogeneity index (HI) for each delivery type.
      RESULTS: No significant difference was found between RapidArc, VMAT and IMRT,
      regarding the minimal and average PTV dose value. The rectum and bladder
      constraints showed no significant variation as well. The PTV hot spot was
      significantly higher for the VMAT plan compared to the RapidArc plan (p=0.007).
      The target CI for VMAT (0.55+/-0.05) and IMRT (0.71+/-0.08) was found to be
      smaller than the RapidArc (0.82+/-0.04) and the difference is statistically
      significant (p=0). The HI, value was found to have no significant difference
      between RapidArc, VMAT and IMRT plan deliveries. CONCLUSIONS: Two TPS are capable
      of producing high-quality treatment plans for prostate cancer. The quality is
      associated with the degree of intensity modulation and the number of incident
      angles. Overall, the RapidArc plans with 2-3 arcs showed better dosimetric
      qualities than the VMAT and IMRT plans.

PMID- 28517098
TI  - SU-E-T-565: Effectiveness of Robust Optimization in Head and Neck IMPT Dose
      Distributions.
AB  - PURPOSE: The effectiveness of IMPT may be significantly diminished by range and
      patient setup uncertainties. The purpose of this presentation is to evaluate the
      ability of robust optimization methods to desensitize H&N IMPT plans to
      uncertainties and their impact on plan optimality. METHODS: We use a robust
      optimization method, in which the objective function value for a given iteration
      is computed using the 'worst case' dose distribution. The conventionally
      optimized PTV-based IMPT plans and robustly optimized plans were generated for 14
      head and neck cancer cases. The dose standard deviation was calculated for every
      voxel and used to compute 'standard-deviation volume histograms' (SVHs). The area
      under SVH curves was used to quantify the plan robustness. In addition, D1cc
      doses for spinal cord and brainstem, mean doses Dmean for oral cavity and
      parotids, and D1% doses for other organs were used to assess plan optimality. D5%
      and D95% doses are used to assess target dose coverage and homogeneity. The plan
      optimality and robustness are then compared statistically by the pair t-tests
      using SPSS 19.0 software. RESULTS: Compared with PTV-based optimization, robust
      optimization provides significantly more robust dose distribution for both
      targets and organs without sacrificing, and possibly even improving, the sparing
      of normal tissues. In addition, our robust optimization method also leads to more
      homogeneous dose distribution in targets with better prescription dose coverage.
      Improvements are statistically significant with p-value smaller than 0.05 for
      almost all end points compared. CONCLUSION: Robust optimization results in
      patient-specific, optimizer-determined, and effectively reduced margins compared
      to a predefined and fixed margin used in the PTV approach. The optimizer can find
      a desired beamlet weight solution from the degenerate solution space so that the
      dose distribution follows the changes in anatomical geometry and is minimally
      perturbed by uncertainties. Our results demonstrate the importance of robust
      optimization. This research is supported by National Cancer Institute (NCI) grant
      P01CA021239, the University Cancer Foundation via the Institutional Research
      Grant program at the University of Texas MD Anderson Cancer Center, and MD
      Andersona?TMs cancer center support grant CA0 16672.

PMID- 28517099
TI  - SU-E-T-605: RapidArc Combined with DIBH Technique for Thoracic Esophageal
      Carcinoma: The Potential Value of Target Immobilization and Reduced Lung Density
      in Dose Escalation.
AB  - PURPOSE: To compare the dosimetric benefits of Rapidarc (RA) combined with deep
      inspiration breath-hold (DIBH) with those of other standard techniques, including
      free breathing (FB) during fixed-field intensity modulated radiation therapy
      (IMRT) and dual arc RA, in the treatment of patients with thoracic esophageal
      carcinoma (EC). METHODS: Ten patients with EC underwent computed tomography (CT)
      scans under 2 respiration conditions: free-breathing (FB) and DIBH. These scans
      were used to generate 3-dimensional conformal treatment plans. For breath-hold
      scans, the patients were brought to reproducible respiration levels using active
      breathing control (ABC) maneuvers. Planning target volumes (PTVs) for FB plans
      included a 0.5 cm margin for setup plus a 1 cm margin equal to the extent of
      tumor motion for respiration. PTVs for DIBH plans included a 0.5 cm margin for
      setup error and a 0.5 cm margin for residual uncertainty in tumor position. Using
      a dose level of 60 Gy to the PTV, three treatment plans were generated: IMRT-FB,
      RA-FB and RA-ABC, and the target and normal tissue volumes were compared, as were
      the dosimetry parameters. RESULTS: On average, the DIBH technique resulted in
      increased lung volumes compared with FB techniques. There was no significant
      differences in gross tumor volume between the two breathing states (p > 0.05);
      but PTV and heart volume were larger for FB than for DIBH (p < 0.05). The overall
      CI and HI for the RA-ABC plan was slightly inferior to those of the IMRT- FB and
      RA-FB plans (p < 0.05 each). With DIBH, the heart was partly out of the beam
      portals and the average mean heart dose was reduced. CONCLUSIONS: Compared with
      conventional FB, RA combined with DIBH significantly reduced cardiac and
      pulmonary doses without compromising the target coverage and may reduce treatment
      toxicity, enabling dose escalation in future prospective studies of patients with
      EC.

PMID- 28517100
TI  - SU-E-T-576: Investigation of Combining Modulated Electron Beams with Intensity
      Modulated Photons for Radiation Therapy of Breast Cases.
AB  - PURPOSE: Modulated electron radiation therapy (MERT) can offer significant
      advantages for breast treatments over conventional radiotherapy in terms of
      sparing distal critical structures. While intensity modulated radiation therapy
      (IMRT) has the advantage of achieving better dose homogeneity inside the target
      combining both MERT and IMRT will be the ideal scenario. The Aim of the present
      study is to investigate the possibility of further improving breast radiation
      therapy using combined MERT/IMRT treatment technique. METHODS: Accurate modeling
      of a prototype motorized electron multileaf collimator was verified in a separate
      study. In this work treatment planning was performed by an in house Monte Carlo
      based inverse planning system. Dose deposition coefficients were calculated using
      MCPLAN and utilizing real patients CTs. Optimization is then conducted based on
      an equivalent uniform dose objective function. MERT and IMRT plans were created
      for different patients. RESULTS: The clinical beneficial outcome for MERT either
      alone or combined with IMRT was investigated based on isodose distributions and
      dose volume histograms. It is shown that MERT can give similar dose distributions
      as IMRT in some cases. For some cases, MERT could be advantageous whenever more
      skin dose was required. In some cases MERT can be identified as the best option.
      It was found that MERT compared to IMRT could introduce hot spots inside the
      target. However this was resolved in combined MERT/IMRT treatment. Dose
      uniformity can be restored with a reduction in the maximum lung and heart
      received dose. CONCLUSION: MERT can improve treatment plan quality for many
      breast patients. In some cases better results can be obtained with a combined
      MERT/IMRT treatment, where a homogeneous dose in the target can be achieved with
      an improvement in the DVH of critical structures. This work has been supported by
      a UICC American Cancer Society Beginning Investigators Fellowship funded by the
      American Cancer Society.

PMID- 28517102
TI  - SU-E-T-598: Clinical Experience of Configuration, Commission and Implementation
      for SmartArc with MOSAIQ R&V System.
AB  - PURPOSE: Clinical experience for configuration, commission and implementation of
      SmartArc with MOSAIQ R&V system. METHODS: SmartArc is Pinnacle's solution for
      VMAT. On July 2011 we updated to Pinnacle 9.0 and purchased SmartArc. A
      standalone Eclipse workstation has been used 3 years for VMAT planning. Our
      clinical setting: Mosaiq 2.2; Varian Trilogy driven by 4DiTC and Varian 21ex
      driven by sequencer. Some key physics parameters have been studied: machine dose
      rate; MLC leaf speed; Leaf motion per gantry rotation. Tabletop was created by
      user to improve the dose accuracy for planning. In-house sandwich phantom was
      used with MapCheck for planner dose verification. A PTW 0.6cc ion chamber was
      included for absolute dose comparison. RESULTS: A copy of current machine data
      with default highest dose rate is recommended. It is due to after 10th iteration
      of optimization, the default dose rate will kick in. 2.5cm/s is the constraint
      for Varian Millennium 120 MLC; a buffer zone of 10% is suggested to reduce the
      MLC error on treatment. 2.25cm/s is used in our configuration. This results in
      MLC interlock if not configured correct. Maximum leaf motion per gantry rotation
      of 0.46cm/degree has to be checked for planning with Mosaiq R&V. Otherwise,
      undeliverable plan will show up sometimes on 4DiTC.Tabletop was exported as a
      DICOM structure from Eclipse to Pinnacle; we created a ROI template based on the
      matched tabletop.QA using in-house phantom for different sites were tested.
      Results for both planner dose and absolute chamber measurement are satisfactory.
      CONCLUSIONS: Special attentions need to be paid for dose rate, MLC leaf speed,
      leaf motion per gantry rotation when configuring SmartArc. Varian 21ex is
      supported but is slow for clinical delivery. Users need to create your own
      tabletop to improve planning accuracy. Conventional commission procedures for
      RapidArc also apply for SmartArc.

PMID- 28517101
TI  - SU-E-T-587: Whole IMRT, Hybrid IMRT and 3D Conformal Plan a Dosimetric Comparison
      for Large Target.
AB  - PURPOSE: To dosimetrically compare the whole-IMRT, hybrid-IMRT (combination of
      IMRT and 3D-CRT) and 3D-conformal radiotherapy (3D- CRT) plans for larger
      targets. METHODS: Five previously treated patients of carcinoma cervix with para
      aortic lymph-nodes (target length 33-34cm) were selected. PTV-P (PTV-Primary),
      PTV-PA (PTV-para-aortic) and organ at risks (OARs) were defined. Three plans were
      generated using Eclipse TPS for Varian CL2300C/D linear accelerator using 6MV
      photon beam. Three plans were: (i) Whole-IMRT: IMRT for both PTV-P and PTV-PA
      (ii) Hybrid-IMRT: IMRT for PTV-P and 3D-CRT for PTV-PA (iii) 3D-CRT: 3D-CRT for
      both PTV-P and PTV-PA. Prescription dose for PTV-P is 50.4Gy and PTV-PA is 45Gy
      in 28 fractions. Coverage index (CI=Target volume covered by prescription
      dose/Target volume), mean doses to bladder, rectum and bowel were used for plan
      comparison by using DVH. Integral dose (liter-Gray) to normal tissue (i.e.,
      patient volume minus PTV-P and PTV-PA) and total monitor units (MUs) required to
      deliver a plan was also noted. RESULTS: The CI for PTV-P is 0.98+/-0.20, 0.96+/
      0.09, and 0.95+/-0.01 for Whole-IMRT, Hybrid-IMRT and 3D-CRT plan and for PTV- PA
      is 0.98+/-0.01, 0.98+/-0.01, and 0.97+/-0.20. Maximum doses to PTV-P are
      5660.85+/-90.85cGy, 5640.35+/-70.35cGy and 5813.80+/-97.40cGy. Maximum doses to
      PTV-PA are 5000.60+/-109.10cGy, 5079.85+/-20.25cGy and 5092.25+/-19.75cGy. Mean
      doses to the bladder are 3810+/-225.80cGy, 3842.10+/-182.70cGy and 5204+/
      98.25cGy for Whole-IMRT, Hybrid-IMRT and 3D-CRT plan, respectively. Mean doses to
      rectum are 3955.35+/-324.95cGy, 3971.15+/-354.15cGy and 4741.20+/-371.60cGy. Mean
      doses to bowel are 2623.35+/-320.85cGy, 2855.30+/-371.05cGy and 3011.7+/
      433.80cGy. Average MUs required to deliver one fraction is 1285+/-87, 1585+/-186,
      485+/-46 for Whole-IMRT, Hybrid-IMRT and 3D-CRT plans, respectively. Higher
      integral doses to normal tissue were observed for whole-IMRT (267.60+/-76 liter
      Gy) followed by hybrid-IMRT (259.20+/-53 liter-Gy) and 3D-CRT (186.30+/-33 liter
      Gy). CONCLUSIONS: Whole-IMRT is useful for larger targets compared to hybrid-IMRT
      in terms of dose conformity, lesser MUs and reduced critical organ doses with
      little compromise on integral dose, where 3D-CRT sacrificed the OAR sparing.

PMID- 28517103
TI  - SU-E-T-569: A Dosimetric Comparison of Helical Tomotherapy versus Intensity
      Modulated Proton for Lung Cancer.
AB  - PURPOSE: To evaluate the dosimetric difference between helical tomotherapy (HT)
      and intensity modulated proton therapy (IMPT) treatment for lung cancer patients.
      METHODS: Five patients treated by HT at University of Wisconsin Carbone Cancer
      Center were selected. HT plans were generated on TomoTherapy treatment planning
      station (TomoTherapy Inc., USA). The field widths were set to 2.5 cm for all
      patients in this study. The IMPT plans were generated using the same planning CT
      and contours with our in-house treatment planning system. Three to five field
      spot scanning IMPT were used to deliver uniform doses to the targets while
      minimizing the irradiated lung volume. The proton spots used has a Gaussian sigma
      of 6mm and are placed on a rectangular grid. The dose distribution of each proton
      spot is calculated using a pencil beam algorithm with tissue heterogeneity
      corrections. All the dosimetric analyses are performed using normalized total
      dose. Alpha/beta ratios were set to 3 for normal tissues and 10 for tumors.
      RESULTS: IMPT plans showed improvement of critical structure avoidance and target
      dose uniformity for all patients. Reductions in mean lung doses of between 81% to
      27% were observed in the IMPT plans relative to the HT. The equivalent uniform
      dose of the target improved from 49.2 Gy in HT plan to 60.04 Gy in IMPT for
      patient #2, and equivalent for other cases. The maximum doses to cord were
      reduced by 20.5 Gy on average using IMPT. In two patient cases, the normal tissue
      complication probabilities were reduced by 53% and 14% with IMPT. CONCLUSION:
      IMPT provides improved dose homogeneity on the target and normal structure
      sparing compared with HT in the treatment of non-small cell carcinoma in lung.
      Significant reduction of mean lung dose was demonstrated, as well as toxicity to
      organs at risk adjacent to the target.

PMID- 28517104
TI  - SU-E-T-609: Improving the Efficiency of VMAT Plan Optimization by Using Sparse
      Decomposition Method.
AB  - PURPOSE: Volumetric modulated arc therapy (VMAT) is capable of delivering highly
      conformable dose distribution efficiently. Its planning is, however, more
      computationally intensive and requires a huge amount of memory space for
      optimization. We present an efficient sparse decomposition method for VMAT plan
      optimization. METHODS: A quadratic objective function with volumetric constraints
      is expressed as a function of the aperture shapes and weights of the incident
      beams. The algorithm generates a sequence of iterates to solve the optimization
      problem. Each step of iteratively reweighed method is to be updated by solving
      the subproblem involving a quadratic (L2) term and a sparsity-inducing regulation
      (L1) term. Through the sparse decomposition techniques of the given problem, the
      deliverable apertures are directly generated. The shape of each aperture is
      iteratively rectified to be a sequencing of arc using the manufacture
      constraints. An initial arc spacing of 8 degree creates 45 beams directions for a
      single arc, 360 degree. The angular separation is equispaced every 2 degree over
      the end of optimization cycle. The optimization is implemented for a Varian
      TrueBeamTM STX linac beams with and without flattening filters available. Three
      clinical cases, head and neck, lung, and prostate, have been studied for the
      purpose of evaluating the planning efficiency and quality of the plans. RESULTS:
      The target dose coverage and critical structure sparing of VMAT plan are
      comparable to those of IMRT plans. The VMAT plan delivers lower doses to other
      OARs while keeping the similar target dose coverage to IMRT plan. The VMAT plan
      optimizations takes less than 3 minutes on average of the cases indicating great
      efficiency compared to existing methods. CONCLUSIONS: The results demonstrate
      that the proposed method provides competent computational efficiency for
      optimizing VMAT plan. The method substantially improves the speed and accuracy of
      VMAT plan optimization and makes future on-treatment adaptive re-planning
      possible.

PMID- 28517105
TI  - SU-E-T-580: Does Arc Therapy Have the Potential to Improve Radiation Treatment of
      Hodgkin's Lymphoma Patients?
AB  - PURPOSE: To evaluate whether arc therapy (helical Tomotherapy and volumetric arc
      therapy; VMAT) is superior to step and shoot IMRT regarding sparing of lungs
      while maintaining adequate planning target volume (PTV) coverage in Hodgkin's
      lymphoma patients . METHODS: Radiation treatment plans for eleven Hodgkin's
      lymphoma patients were created employing the following techniques: coplanar and
      noncoplanar Step & Shoot IMRT, VMAT and Tomotherapy, i.e., for every patient 4
      different treatment plans were created. The IMRT and VMAT planning was performed
      with Pinnacle software (v. 8 and 9, Philips) suitable for delivery with an Elekta
      linear accelerator, Tomotherapy plans were calculated with Tomotherapy planning
      software (v. 3.4). Four patients received a single prescription dose of 30 or 36
      Gy, and 7 patients received a simultaneous integrated boost (30 Gy/36 Gy).
      Treatment plans were optimized such that the normal tissue constraints for the
      lung [volume receiving more than 20 Gy (V20) is less than 30% and mean lung dose
      (MLD) is less than 14 Gy] were met, even if PTV coverage (V95%=99%) had to be
      sacrificed. RESULTS: All 4 techniques delivered clinically acceptable treatment
      plans. Tomotherapy achieved the highest dose homogeneity in the PTV and highest
      dose coverage of the boost volume (on average 98% versus 96% for the other 3
      techniques). Since lung sparing was the first planning objective, all techniques
      scored equally well for V20 en MLD. CONCLUSIONS: The strength of arc therapy lies
      in the large number of beamlets entering the patient from a high number of
      angles. For Hodgkin's lymphoma patients this does not automatically translate
      into a superior treatment due to the high weight on the lung objectives limiting
      the number of beamlets allowed to pass through the lung. This means that for
      Hodgkin's lymphoma arc therapy has no added value for sparing of the lungs.

PMID- 28517106
TI  - Tunable Supramolecular Assembly and Photoswitchable Conversion of
      Cyclodextrin/Diphenylalanine-Based 1D and 2D Nanostructures.
AB  - A photocontrolled, interconvertible supramolecular 2D-nanosheet/1D-nanotube
      system was constructed through the supramolecular assembly of adamantanyl
      modified diphenylalanine with azobenzene-bridged bis(beta-cyclodextrin). The
      nanosheet exhibited a greater fluorescence enhancement effect than the nanotube.
      Significantly, these nanosheets and nanotubes could interconvert via the
      photocontrolled trans/cis isomerization of azobenzene linkers in bis(beta
      cyclodextrin), and this photo-switchable one-dimensional/two-dimensional
      morphological interconversion was reversible and recyclable. This enables
      convenient routes to highly ordered nanostructures with various morphologies and
      dimensions that can be controlled by external stimuli.

PMID- 28517107
TI  - Right coronary artery coronary sinus fistula with coronary sinus ostium stenosis.
AB  - Coronary artery fistula (CAF) is a rare anomaly of the coronary artery. The
      draining site of a right coronary artery (RCA) fistula may usually be the right
      ventricle, right atrium, or pulmonary artery. Here, we present a patient with
      right coronary artery to coronary sinus fistula (RCACSF) complicated by
      aneurysmal dilatation of the coronary sinus (CS) and stenosis of CS ostium.

PMID- 28517108
TI  - Goals of medical students participating in scholarly concentration programmes.
AB  - OBJECTIVES: Scholarly concentration (SC) programmes are increasingly common in
      medical school curricula, fostering student participation in mentored research.
      Endpoints including publication rates and impact on career path have been
      reported, but student goals have not been described. We describe how career plans
      and gender impact the importance of students' SC-related goals. Understanding
      student goals may enhance mentorship of professional development and self
      directed learning skills. METHODS: First-year students at two US medical schools
      were surveyed. Students reported intentions regarding career-long research and
      specialty interests. Using a 5-point scale, students assigned importance to 13
      goals (eight skill-related goals, four accomplishment-related goals and
      mentorship), Composite scores for skills-related and accomplishment-related goals
      were used for analysis. Regression analyses, controlling for school, were used to
      determine whether intentions regarding career-long research, interest in highly
      competitive residency or gender were associated with increased importance of
      different goals. RESULTS: We surveyed 288 first-year medical students and
      received 186 responses (64.6% response rate). Compared with their peers, students
      interested in career-long research placed more importance on both skill-related
      goals (beta coefficient, 1.87; 95% confidence interval [CI], 1.03-2.71; p <
      0.001) and accomplishment-related goals (odds ratio [OR], 1.71; 95% CI, 1.09
      2.69; p = 0.02). By contrast, compared with their peers, students interested in
      highly competitive specialties placed more importance only on accomplishment
      related goals (OR, 2.18; 95% CI, 1.15-4.11; p = 0.02). Compared with men, women
      placed more importance on mentorship (OR, 2.47; 95% CI, 1.23-4.97; p = 0.01) and
      were less likely to be interested in highly competitive residencies (39.4% versus
      54.9%, p = 0.04). CONCLUSIONS: Gender and career plans are associated with
      importance of SC-related goals in the first year of medical school. This
      knowledge enables faculty to promote students' appreciation of important learning
      goals in the setting of student research, which may help students engage in self
      directed learning across their medical education.

PMID- 28517109
TI  - The studies of ParA and ParB dynamics reveal asymmetry of chromosome segregation
      in mycobacteria.
AB  - Active segregation of bacterial chromosomes usually involves the action of ParB
      proteins, which bind in proximity of chromosomal origin (oriC) regions forming
      nucleoprotein complexes - segrosomes. Newly duplicated segrosomes are moved
      either uni- or bidirectionally by the action of ATPases - ParA proteins. In
      Mycobacterium smegmatis the oriC region is located in an off-centred position and
      newly replicated segrosomes are segregated towards cell poles. The elimination of
      M. smegmatis ParA and/or ParB leads to chromosome segregation defects. Here, we
      took advantage of microfluidic time-lapse fluorescent microscopy to address the
      question of ParA and ParB dynamics in M. smegmatis and M. tuberculosis cells. Our
      results reveal that ParB complexes are segregated in an asymmetrical manner. The
      rapid movement of segrosomes is dependent on ParA that is transiently associated
      with the new pole. Remarkably in M. tuberculosis, the movement of the ParB
      complex is much slower than in M. smegmatis, but segregation as in M. smegmatis
      lasts approximately 10% of the cell cycle, which suggests a correlation between
      segregation dynamics and the growth rate. On the basis of our results, we propose
      a model for the asymmetric action of segregation machinery that reflects unequal
      division and growth of mycobacterial cells.

PMID- 28517110
TI  - Outcomes after medical and surgical interventions in horses with temporohyoid
      osteoarthropathy.
AB  - BACKGROUND: Temporohyoid osteoarthropathy (THO) is a cause of neurological
      disease in horses that is characterised by facial and vestibulocochlear nerve
      deficits. Studies reporting and comparing survival following medical or surgical
      treatment of THO are lacking. OBJECTIVES: To compare survival and prognosis in
      horses with THO treated medically or surgically, and to report surgical
      complications. STUDY DESIGN: Retrospective study. METHODS: The medical records of
      horses diagnosed with THO were retrieved, and data on signalment, clinical signs
      and duration, corneal ulceration and bilateral occurrence were recorded.
      Neurological severity was graded according to clinical signs. Preoperative
      radiographic and endoscopic images were graded according to the severity of
      changes. Factors potentially affecting survival and treatment were compared using
      Cox proportional hazards regression. RESULTS: A total of 77 horses were
      identified as having THO during the period 1990-2014. Of these, 25 horses
      underwent ceratohyoid ostectomy (CHO) and eight underwent partial stylohyoid
      ostectomy (PSHO). Thirteen of 20, one of 25 and one of eight horses treated by
      medical therapy, CHO and PSHO, respectively, died or were subjected to euthanasia
      as a consequence of THO. Compared with CHO, medical therapy was significantly
      associated with nonsurvival, but there were no significant differences in
      survival between horses undergoing PSHO and medical therapy. The duration of
      clinical signs, and neurological, radiographic and endoscopic grades were not
      associated with survival of THO. However, the age of the horse was significantly
      associated with poorer survival. Survival time was significantly shorter in the
      medical therapy group compared with the two surgical groups combined, but did not
      differ significantly between the two surgical groups. No significant difference
      between groups was seen in the incidence of surgical complications (33.3% in the
      PSHO and 22.2% in the CHO group). MAIN LIMITATIONS: This was a nonrandomised
      study of treatment effects on survival and included a low number of cases.
      CONCLUSIONS: The survival prognosis in horses with THO is good to excellent in
      those submitted to surgical intervention, and fair in those treated with medical
      therapy alone.

PMID- 28517112
TI  - Patterns and correlates of adherence to self-monitoring in lung transplant
      recipients during the first 12 months after discharge from transplant.
AB  - Self-monitoring of lung function, vital signs, and symptoms is crucial for lung
      transplant recipients (LTRs) to ensure early detection of complications and
      prompt intervention. This study sought to identify patterns and correlates of
      adherence to self-monitoring among LTRs over the first 12 months post-discharge
      from transplant. This study analyzed existing data from the usual care arm
      participants of a randomized clinical trial who tracked self-monitoring
      activities using paper-and-pencil logs. Adherence was calculated as the percent
      of days LTRs recorded any self-monitoring data per interval: hospital discharge-2
      months, 3-6 months, and 7-12 months. The sample (N=91) was mostly white (87.9%),
      male (61.5%), with a mean age of 57.2+/-13.8 years. Group-based trajectory
      analyses revealed two groups: (i) moderately adherent with slow decline (n=29,
      31.9%) and (ii) persistently nonadherent (n=62, 68.1%). Multivariate binary
      logistic regression revealed the following baseline factors increased the risk in
      the persistently nonadherent group: female (P=.035), higher anxiety (P=.008), and
      weaker sense of personal control over health (P=.005). Poorer physical health
      over 12 months were associated with increased risk in the persistently
      nonadherent group (P=.004). This study highlighted several modifiable factors for
      future interventions to target, including reducing post-transplant anxiety, and
      strengthening sense of personal control over health in LTRs.

PMID- 28517114
TI  - SU-E-T-108: 3D Measurement of Neutron Dose from a Novel Neutron Imaging
      Technique.
AB  - PURPOSE: We have been developing a fast-neutron spectroscopic technique to
      quantitatively image the distribution of elements in the body using quasi
      monochromatic neutron beams. Previously, we demonstrated the ability of the
      technique to quantify specific elements in the liver and breast while limiting
      radiation dose to clinically acceptable levels. Here we present the results of a
      physical dose measurement performed through neutron irradiation of 3D PRESAGE
      dosimetry phantoms. METHODS: Two PRESAGE optical-CT dosimeters were placed inside
      a physical phantom of the human torso and irradiated with 8 MeV neutrons produced
      via the 2H(d,n) reaction using a tandem Van-de-Graaff accelerator. The
      dosimeters, measuring 10 cm and 4 cm in diameter, were located in regions
      corresponding to the liver (10 cm), and the kidney (4 cm). Irradiation was
      performed with the neutron beam incident directly on the larger dosimeter.
      Cumulative neutron fluence incident upon each dosimeter was determined using an
      aluminum-foil activation technique. Following irradiation, the change in optical
      density in both dosimeters was measured to determine the relative irradiation and
      dose distribution in each volume. RESULTS: Both PRESAGE dosimeters exhibited
      detectable changes in optical density corresponding to the dose deposited in the
      volume. The two dosimeters registered doses of 8.5 Gy (direct incidence, 4.5 hour
      irradiation) and 0.25 Gy (off-axis, 20 hour irradiation), respectively. The
      larger dosimeter showed highest intensity at the entry point of the beam with
      exponential drop-off along the beam direction. The smaller dosimeter registered a
      more uniform change in intensity, consistent with the higher incidence of
      scattered neutrons at this location. CONCLUSION: The results demonstrate the
      utility of PRESAGE dosimeters in measuring dose from neutron irradiation and
      highlight the difference in relative doses between primary and proximal organs
      when exposed to neutron beams. This work was supported by the United States
      Department of Energy, Office of Nuclear Physics under Grant No. DE-FG02
      97ER41033, the National Cancer Institute under grant R01CA100835, and by the
      Department of Defense under award W81XWH-09-1-0066.

PMID- 28517113
TI  - Differences between two strains of Ceriporiopsis subvermispora on improving the
      nutritive value of wheat straw for ruminants.
AB  - AIM: This study evaluated differences between two strains of Ceriporiopsis
      subvermispora on improving the nutritive value and in vitro degradability of
      wheat straw. METHODS AND RESULTS: Wheat straw was treated with the fungi for 7
      weeks. Weekly samples were analysed for ergosterol content, in vitro gas
      production (IVGP), chemical composition and lignin-degrading enzyme activity.
      Ergosterol data showed CS1 to have a faster initial growth than CS2 and reaching
      a stationary phase after 3 weeks. The IVGP of CS1-treated wheat straw exceeded
      the control earlier than CS2 (4 vs 5 weeks). CS1 showed a significantly higher (P
      < 0.001) selectivity in lignin degradation compared to CS2. Both strains showed
      peak activity of laccase and manganese peroxidase (MnP) at week 1. CS1 showed a
      significantly higher (P < 0.001) laccase activity, but lower (P = 0.008) MnP
      activity compared to CS2. CONCLUSION: Both CS strains improved the nutritive
      value of wheat straw. Variation between strains was clearly demonstrated by their
      growth pattern and enzyme activities. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      differences among the two strains provide an opportunity for future selection and
      breeding programs in improving the extent and selectivity of lignin degradation
      in agricultural biomass.

PMID- 28517116
TI  - SU-E-T-91: Validation of Geant4 Physics for Ionization Chamber Calculations in
      Radiotherapy Photon Beams.
AB  - PURPOSE: To determine the accuracy of the GEANT4 Monte Carlo toolkit for
      ionization chamber calculations in radiotherapy photon beams. METHODS: First, we
      used the Fano cavity example included in the GEANT4 distribution to validate
      calculations under Fano conditions. We determined a combination of parameters and
      physics list that provided results consistent within +/- 0.5% with the Fano
      theorem. Next we performed simulations to investigate the accuracy of using
      GEANT4 for ionization chamber calculations. Eight ionization chambers were
      modeled using detailed manufacturer specifications including A1, A1SL, NE2571,
      PTW30010, PTW30012, PTW31010, PTW31014 and PTW31016. The absorbed dose to water
      for a cylindrical water cavity and the absorbed dose to air in the ionization
      chambers' cavities were scored for 1.25 MeV photons. The ratio of these
      quantities was then compared to values from EGSnrc simulations. RESULTS:
      Simulations using the Fano cavity example yielded results within +/- 0.5% with
      the Fano theorem across 1.25, 3 and 4 MeV incident photon energies. The most
      accurate and consistent results were obtained using the G4eIonisation ionization
      model and G4GoudsmitSaundersonMscModel multiple scattering (MS) model with a
      maximum step size limitation of 0.001 mm, which yielded results accurate to +/-
      0.3% for all energies. This set of parameters and physics processes as well as
      the G4UrbanMscModel93 MS model were used for the ionization chamber calculations.
      The calculated quantities were compared to those used in Muir and Rogers 2010
      (Med. Phys. 37: 5939-5950) and agreed to within sub-percentage differences for
      most chambers. CONCLUSIONS: The GEANT4 toolkit can achieve sub-percentage
      accuracy for ionization chamber calculations in radiotherapy photon beams. This
      is achieved by using either the G4GoudsmitSaundersonMscModel or G4UrbanMscModel93
      MS models. Although less accurate (+/- 0.5%), simulations employing the
      G4UrbanMscModel93 MS model are on average two orders magnitude faster than that
      of the G4GoudsmitSaundersonMscModel MS model (+/- 0.3%). Natural Sciences and
      Engineering Research Council of Canada.

PMID- 28517115
TI  - SU-E-T-119: Evaluation of New VMAT and IMRT Planning QA Devices: Portal Dosimetry
      Vs Compass.
AB  - PURPOSE: Wide spread clinical use of advanced radiation treatment delivery
      techniques such as volumetric modulated arc therapy (VMAT) and IMRT needs an easy
      to-use, well-defined, and effective quality assurance (QA) system to ensure the
      accuracy of dose delivery. The comprehensive evaluation of two delivery QA
      systems (DQA) (Portal Dosimetry and Compass) for the advanced radiation delivery
      techniques is necessary for the clinical setting. METHODS: Portal Dosimetry QA
      system with Varian PortalVision (PV) provides a quantitative comparison of
      measured electronic dose profile to a predicted dose profile with Varian's
      EclipseTM treatment planning system (TPS) for the VMAT and IMRT plans.
      Quantitative comparisons of the two images, including dose difference, gamma
      analysis, points dose measurements, and line profiles are easily acquired in two
      dimensions. Meanwhile, Compass system with MatriXX can provide an accurate three
      dimensional quantitative analysis of dose delivery. We applied the two planning
      QA systems to our RapidArc patient- specific QAs. Validation of the Compass and
      Portal Dosimetry systems were performed with ionization chamber measurements for
      absolute dosimetry and film measurements for gamma index calculations for phantom
      and patient treatment plans. RESULTS: Compass system was very sensitive to the
      MLC leaf gap variations in three dimensional gamma analyses. However, Compass
      system was not enough to fix the errors in dosimetric leaf gap by itself. DQA
      process with Portal Dosimetry took approximately 6 minutes for the two Arcs VMAT
      plan. Compass took about 40 minutes for the same plan in our first clinical
      trial. For the three typical IMRT and VMAT plans, the two systems showed the same
      passing rates in 95% pixels passing gamma criteria 3%/3mm. CONCLUSIONS: Portal
      Dosimetry DQA system has the advantages of effectiveness and practicality in the
      clinical setting. On the other hand, Compass was the next supportive system
      because of its accuracy and reality with patient's anatomy.

PMID- 28517117
TI  - SU-E-T-130: IMAT Patient Specific Quality Assurance Using ArcCHECK Diode Array
      Detector.
AB  - PURPOSE: To evaluate the IMAT patient specific quality assurance (QA) performed
      using ArcCHECK detector array in reference with standard ion chamber for routine
      clinical use. METHODS: Twelve patient plans having different tumor sites chosen
      for this study. On Eclipse planning system,IMAT patient plans were calculated on
      ArcCHECK phantom inserted with Ion chamber using superposition algorithm.
      ArcCHECK is a cylindrical phantom with a three-dimensional array of 1386 diode
      detectors, arranged in a spiral pattern, with 10 mm diode spacing. These plans
      delivered from Clinac-iX linac equipped with 120 MLC. Point dose and Dose/fluence
      map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode
      array detector respectively. Point doses, dose/fluences map and dose at central
      axis (CAX) on ArcCHECK phantom were compared with their respective TPS calculated
      values. RESULTS: The ion chamber measurements are in good agreement with TPS
      calculated doses. Mean difference between them is 0.50% with standard deviation
      is 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber base
      absolute dose measurements is 0.9996. These results demonstrate a strong
      correlation between the absolute dose predicted by our TPS and the measured dose.
      The precision of the TPS software was 0.9999, and its accuracy was 0.9997.The
      agreement between ArcCHECK doses and TPS predictions on the CAX, shown CCC of
      0.9978 (the mean difference in the central axis dose is 2.11%). The 95%
      Confidence Interval is from 0.9932 to 0.9995. In gamma analysis of dose/fluence
      map the mean passing rate was 98.53% for 3% dose difference and 3mm distance to
      agreement. CONCLUSIONS: The IMAT patient specific QA with Ion chamber and
      ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good
      agreement observed between ArcCHECK measured and TPS calculated. Hence it can be
      used for routine IMAT QA.

PMID- 28517118
TI  - SU-E-T-101: Dosimetry Intercomparison for a Synchrotron-Produced Monochromatic X
      Ray Beam.
AB  - PURPOSE: This study performed a dosimetry intercomparison for synchrotron
      produced monochromatic x-ray beams. Ion chamber depth-dose measurements in a
      polymethylmethacrylate (PMMA) phantom were compared with the product of MCNP5
      Monte Carlo calculations of dose per fluence and measured incident fluence at 25
      and 35 keV. The ion chamber measurements are being used to calibrate dose output
      for cell irradiations designed to investigate photoactivated Auger electron
      therapy at the LSU Center for Advanced Microstructures and Devices (CAMD)
      synchrotron facility. METHODS: Monochromatic beams of 25 and 35 keV were
      generated on the tomography beamline at CAMD. A cylindrical, air-equivalent ion
      chamber was used to measure the ionization created in a 10*10*10-cm3 PMMA phantom
      at depths of 0.6 - 7.7 cm. AAPM TG-61 protocol was applied to convert measured
      ionization into dose. MCNP5 simulations of the irradiation geometry were
      performed to determine the dose deposition per photon fluence in the phantom.
      Photon fluence was determined using a NaI detector to make scattering
      measurements of the beam from a polyethylene target at angles 15 - 60 degrees.
      Differential Compton and Rayleigh scattering cross sections were used to derive
      the incident fluence. RESULTS: At 35 keV dose measurements for equal exposures
      determined using the MCNP5-fluence results underestimated those of the ion
      chamber by 1.8 - 4.8% for PMMA depths from 0.6 - 7.7 cm, respectively. At 25 keV
      there was an overestimate of 6.6 - 1.9%. CONCLUSIONS: These results show that TG
      61 ion chamber dosimetry, used to calibrate the dose output for the cell
      irradiations, is accurate within approximately 7% for beam energies 25-35 keV.
      This research was supported by contract W81XWH-10-1-0005 awarded by The U.S. Army
      Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014.
      This report does not necessarily reflect the position or policy of the
      Government, and no official endorsement should be inferred.

PMID- 28517119
TI  - SU-E-T-141: Dosimetry and Error Analysis of HDR Brachytherapy Tandem Applicator
      Using A16 Microchamber and Monte Carlo Simulation.
AB  - PURPOSE: Absolute dosimetry with the associated uncertainties for 192Ir High Dose
      Rate (HDR) Brachytherapy Tandem applicator are presented using A16 microchamber
      and Monte Carlo simulation. The results are compared to the TG-43 protocol.
      METHODS: An A16 Exradin MicroChamber, MCNPX 2.6 Monte Carlo simulation code and
      PTW farmer chamber with an ADCL calibration coefficient were used in this work.
      The A16 microchamber was calibrated using MCNPX simulation and PTW farmer
      chamber. Statistical and systematic uncertainty analyses associated with each
      experimental technique were analyzed quantitatively using MCNPX 2.6 to evaluate
      source positional error, Tandem positional error, phantom size effect, volume
      averaging, stem and wall effects, and Tandem effect. RESULTS: A16 microchamber
      was calibrated according to the AAPM TG-21 protocol and resulted in a value of
      3.21E+09 Gy/C for Ngas in 60CO. To use the A16 with 192Ir spectrum, a correction
      factor of 1.13 was generated along the source transverse axis using MCNPX to
      account for energy difference. Absolute dose and uncertainty analyses along the
      transverse axis of a Tandem applicator were calculated using MCNPX and A16
      microchamber and compared to the TG-43 protocol. The generated overall
      uncertainties associated with the A16 microchamber are 22%, 17%, 15%, 15%, 16%,
      17%, and 19% at 1cm, 2cm, 3cm, 4cm, and 5cm, respectively. CONCLUSIONS: In this
      work, the author investigated the absolute dosimetry for 192Ir HDR brachytherapy
      for a Tandem applicator using A16 microchamber and compared the results to the TG
      43 protocol. A16 microchamber has an effective volume of 0.007cc which makes it
      suitable to measure extremely small field sizes and enables high spatial
      resolution while minimizing volume averaging near the source. Furthermore, the
      author also investigated and analyzed the systematic and statistical
      uncertainties associated with A16 experimental dosimetry as recommended by AAPM
      TG-138 and GEC-ESTRO. Based on this work, dosimetry of HDR brachytherapy using
      A16 microchamber can be used, within uncertainties, as an alternative or
      redundant for the LiF TLDs.

PMID- 28517120
TI  - SU-E-T-144: Daily and Monthly Quality Assurance with TomoDose.
AB  - PURPOSE: Examine the use of TomoDose for Tomotherapy quality assurance. METHODS:
      Baseline TomoDose profiles are acquired annually in accordance with TG-148.
      During monthly quality assurance, TomoDose is irradiated with a static beam and
      referenced to baseline. Differences between superimposed profiles are evaluated
      monthly. TomoDose is further utilized in verifying transverse laser alignment.
      The TomoDose is aligned to virtual isocenter lasers and statically irradiated
      with a 40cm * 5.02cm treatment beam. Next, the TomoDose's internal diodes are
      imaged using the MVCT. Transverse laser, imaging beam, and treatment beam field
      center are verified to less than 1mm coincidence difference. For daily TomoDose
      irradiation the couch is set to a fixed height and irradiated. The dose to the
      central axis and dose rate is recorded. To check energy, the measurement is
      repeated with an aluminum block placed centrally on the TomoDose. The output
      reading relative to the dose rate is compared to the baseline determined at the
      time of monthly verification. A ratio of the output and energy readings serves as
      a daily energy constancy check. RESULTS: Over 28 months, for nominal field sizes
      of 1.05, 2.50, and 5.02cm, TomoDose measured an average field size of 1.10, 2.51,
      and 5.02cm with maximum deviations of 0.09, 0.09, and 0.10cm, respectively. For
      transverse laser alignment, TomoDose software calculates beam center location. We
      have found the alignment to be sensitive to sub-millimeter changes. Our nominal
      daily energy ratio is 0.689. We have observed a decline from an estimated 0.693
      to 0.680 with target wear, providing a good indicator of degradation.
      CONCLUSIONS: TomoDose serves as a reliable constancy device with added benefits
      of verifying transverse laser alignment and predicting target health. I own
      common stock in Accuray (Tomotherapy).

PMID- 28517121
TI  - SU-E-T-93: High Dynamic Range Scanning for Optical-CT in 3D Dosimetry.
AB  - PURPOSE: The recent emergence of powerful, fast and high-resolution 3D dosimetry
      techniques brings exciting potential to radically strengthen the foundations of
      quality-assurance in radiation therapy, and hence treatment efficacy. This work
      presents a new acquisition method for 3D dosimetry by optical-computed-tomography
      (optical-CT), which can improve accuracy when imaging strongly attenuating
      dosimeters (e.g. large or heavily dosed). METHODS: The method involves acquiring
      optical-CT projection images where the intensity of the light source is increased
      as much as possible without causing detector saturation within the dosimeter.
      This improves signal-to-noise in dark regions of the dosimeter, but flood-field
      and regions outside the dosimeter are unuseable due to saturation. The problem of
      acquiring a useable flood is solved by acquisition at a reduced shutter opening
      time. The non-saturated flood is then scaled up for use with projections, by the
      ratio of shutter times. The method relies on linearity of signal with shutter
      time, which is investigated here. The method is evaluated by application to a
      range of dosimeters with varying degrees of strong attenuation. RESULTS: The
      relationship between signal and shutter time in the flood was found to be highly
      linear, a key enabling result for this method. When applied to moderately
      attenuating dosimeters, the new method agrees with the standard method to a high
      degree (<1% deviation on average). For very dark dosimeters, the new method was
      found to have greatly improved signal-to-noise (a factor of 2-3 times better) in
      the darkest regions and eliminated streak artifacts present in reconstructions
      using the standard acquisition method. CONCLUSIONS: A new optical-CT acquisition
      method is presented which yields improved signal-to-noise for dosimetry
      measurements in strongly attenuating dosimeters. A further important advantage is
      the method does not require any tinting of the refractively-matched fluid in the
      optical-CT water-bath, which greatly increases convenience and practicability.
      Grant - R01CA100835.

PMID- 28517122
TI  - SU-E-T-132: Investigation of Photon and Proton Overlapping Fields in PRESAGE-
      Dosimeters.
AB  - PURPOSE: To evaluate the effects of overlapping dose volumes for varying field
      arrangements in two formulations of PRESAGE(r): one intended for, and irradiated
      with, proton beams and the other photon beams. METHODS: For each treatment
      modality (photon, proton), three overlapping field setups were performed. These
      included a stationary dosimeter irradiated over six fractions, a dosimeter
      shifted laterally to the field to deliver a dose plateau in two fractions, and a
      dosimeter rotated on its axis to deliver a two-field (for protons) and four-field
      (for photons) box treatment overlapping in the center of the dosimeter. All
      subsequent fractions were given within ten minutes and never less than one minute
      apart. Two cylindrical PRESAGE(r) dosimeters approximately 7.5 cm in length by
      7.5 cm in diameter were irradiated for each setup. The dosimeters were paired,
      with one dosimeter given total dose by a single fraction while the other followed
      one of the overlapping field setups. The dosimeters were analyzed using an
      optical CT scanner and exported to the CERR environment where the doses were
      compared between paired dosimeters. RESULTS: Dose profile comparisons showed
      relative dose agreement between paired dosimeters within 5% along the SOBP region
      of the proton formulation. In the case of the fractionated proton irradiation,
      there was an over-response while other setups resulted in under-responses. Dose
      agreement between the photon dosimeter treated with six fractions showed a dose
      under-response within 11% and never less than 5%. Future measurements will
      include the remaining field setups. CONCLUSIONS: The proton formulation of
      PRESAGE(r) showed good dose agreement between single and multiple field
      irradiations. While the photon formulation had slightly less agreement,
      additional field setup comparisons may show improved results. These results will
      aid future measurements of overlapping field treatment plans delivered to
      PRESAGE(r) for treatment verification for proton and photon 3D dosimetry.

PMID- 28517123
TI  - SU-E-T-103: Three-Dimensional Measurements of Dose and LET from a Proton Beam via
      Polymer Gel Dosimetry.
AB  - PURPOSE: To obtain and assess the accuracy of 3D dose distributions and LET maps
      from a passively-scattered proton beam through the use of LET-dependent and LET
      independent polymer gel formulations. METHODS: Dose measurements were performed
      with BANG3-Pro2 (MGS Research, Inc, Madison, CT) polymer gel dosimeters. The
      dosimeters were mixed from kits and were poured into 14.5 cm high by 15 cm
      diameter acrylic cylinders. For LET measurements, a new BANG3-Pro variant
      intended for use as an 'LET- meter' was employed. Initial irradiations were
      performed using a 200 MeV passively scattered proton beam with a 4 cm spread out
      Bragg peak (SOBP), delivering a physical dose of 3 Gy to the center of the SOBP.
      Dosimeters were read out using the OCTOPUS-IQ (MGS Research, Inc, Madison, CT)
      optical CT scanner. The optical densities measured in the gel were compared
      against ion chamber data to assess the accuracy of the dosimeter. RESULTS:
      Initial analysis indicates 80% of points measured along the central axis agreed
      with ion chamber data at the +/-5%/+/-3mm level in the sensitive region of the
      gel. An artifact in the reconstructed image produced inaccurate readings beyond
      the depth of 50% dose on the distal edge of the SOBP, resulting in the majority
      of the agreement failures. CONCLUSIONS: BANG3-Pro2 polymer gel dosimeters
      demonstrate promise as a 3D dosimeter for use in proton therapy. The dosimetric
      data obtained to date will be used as the baseline measurement against which the
      LET-sensitive BANG3-Pro formulation will be compared for the measurement of
      proton LET.

PMID- 28517124
TI  - SU-E-T-114: Characterization of the Spatial Response Functions of Ionization
      Chambers for Photon Beam Dosimetry.
AB  - PURPOSE: The finite extension of an ionization chamber gives rise to a spatial
      averaging effect, known as the "volume effect". In order to provide the
      appropriate corrections, the response functions along its lateral and
      longitudinal directions are characterized using Gaussian distributions, whose
      standard deviations slat and slong have been determined for a large set of
      clinical dosimeters. METHODS: Nine cylindrical ionization chambers, two parallel
      plate chambers and two 2D ionization chamber arrays have been examined by
      scanning rectangular photon fields along their short axes. The true profiles D(x)
      were known from scans with a small Si diode. The ionization chambers were aligned
      with their symmetry axes either perpendicular or parallel to the scan direction
      in order to obtain slat and slong separately. In a search process, D(x) was
      numerically convolved with normalized one-dimensional Gaussian kernels K(x) of
      varying s. The best fit between the convolution product D(x) * K(x) and the
      measured profile M(x) of the ionization chamber was used to determine parameters
      slat and slong of the Gaussian kernels. RESULTS: For both the lateral and
      longitudinal directions, very good agreement was found between M(x) and the
      convolution products of D(x) with Gaussian kernels K(x). For all chambers, their
      2s values are similar to the cavity dimensions, which means that the "tails" of
      the Gaussian response functions reach into the exterior of the chambers, - an
      effect of the ranges of the secondary electrons. At higher photon energies
      response functions K(x) are slightly wider, but no detectable depth dependence
      has been observed. CONCLUSIONS: We have shown that the response functions of
      ionization chambers can be described by Gaussian distributions, confirming
      earlier observations, and we determined their standard deviations in both the
      lateral and longitudinal directions. Using these response functions, appropriate
      correction methods determined to eliminate the volume effect can be applied.

PMID- 28517125
TI  - SU-E-T-86: Development and Implementation of the Use of Optically Stimulated
      Luminescent Detectors in the Radiological Physics Center Anthropomorphic Quality
      Assurance Phantoms.
AB  - PURPOSE: To study the angular dependence of optically stimulated luminescence
      dosimeters (OSLD) in the Radiological Physics Center anthropomorphic quality
      assurance pelvic phantom to provide accurate dosimetric measurements as a
      replacement for TLD. METHODS: A spherical phantom was constructed to investigate
      the angular response of the OSLD as oriented in the RPC pelvic phantom. Three
      OSLD per irradiation angle, placed at the center of the spherical phantom, were
      irradiated with 100 cGy from six different angles. The angular response at each
      angle was determined relative to the OSLD response when the beam was incident
      normally on the OSLD surface. A pelvic phantom dosimetry insert was modified to
      include both TLD and OSLD. Three treatment plans were developed in Pinnacle v9.0
      and one in Accuray's Multiplan, each with increasing angular beam delivery (4
      field, IMRT, SmartArc, CyberKnife) for the pelvic phantom using a common dose
      prescription and constraints. Each plan was delivered to the phantom three times,
      containing two TLD and two OSLD, oriented in the transverse plane, at the center
      of the PTV. The dose delivered to the TLD and OSLD was calculated for each
      treatment and then compared. RESULTS: The angular dependence correction factor
      for the spherical phantom was found to be uniformly 1.041 +/- 0.003 from single
      beam edge-on irradiations. The angular dependence correction in the pelvic
      phantom from multiple beam orientation irradiations was 1.024 +/- 0.002, such
      that the OSLD dose agreed with the TLD dose. Applying the OSLD pelvic phantom
      correction factor, the RPC measured dose to planning system calculated dose ratio
      was 0.995 +/- 0.009. The established RPC phantom TLD dose to calculated dose
      ratio was 0.995 +/- 0.010. CONCLUSIONS: An anthropomorphic phantom OSLD angular
      dependence correction factor was established such that the final OSLD dose
      measurements agreed with RPC's TLD dose measurements to within 1%. Work supported
      by grant CA 10953, awarded by NCI, DHHS.

PMID- 28517126
TI  - SU-E-T-125: High-Resolution Linear Diode Array for Use in Stereotactic Beam
      Commissioning.
AB  - PURPOSE: Task Group 106 discusses detector arrays and their usefulness in "soft
      wedge" profile measurements. This study verifies an extension of their use; where
      a high-resolution linear diode array is used to measure profile scans for use in
      commissioning stereotactic beam. Small-field data is acquired with the LDA-99sc
      (IBA Dosimetry America, Memphis, TN), an array of 99 two-mm-diameter Hi-pSi
      diodes. These data are compared to data collected during serial scanning with an
      IBA SFD stereotactic diode. METHODS: Field measurements were taken at varying
      depths using an LDA-99sc in 1*1 cm2 , 2*2cm2 , and 3*3cm2 fields of a Trilogy
      accelerator (Varian Medical Systems, Palo Alto, CA). These scans were duplicated
      in resolution and sample rate with an SFD scanning diode. Both techniques
      acquired point data in 1.0mm increments. RESULTS: In identical conditions, the
      LDA-99sc provided readings with significantly less signal fluctuation than with
      traditional diode scanning; which is attributed to the reduction of water motion
      associated with detector travel during traditional scanning. This smoother data
      precluded the use of smoothing and filtration algorithms; allowing the beam to be
      modeled using raw data. The LDA-99sc measured an average penumbra of 0.1 mm wider
      than that which was measured with the diode. The LDA-99sc also measured an
      average field size of 0.3mm wider than that which was measured with the diode.
      With respect to time, a single profile scan (30cm-depth, 3*3cm2 field) using the
      LDA-99sc took 31 seconds, while a diode scan took 229 seconds. CONCLUSIONS: The
      LDA99 provided accurate commissioning-grade small-field beam profile data, as
      verified by comparison with diode scans, with a reduction of uncertainty in
      readings and a substantial reduction in time. Variation in penumbra and beam
      widths were deemed acceptable and can be attributed to the LDA-99sc data being
      raw, while the diode data was processed. Research supported in-part by IBA
      Dosimetry America.

PMID- 28517127
TI  - SU-E-T-97: Intra and Inter Variability in Beam Data Commissioning among Water
      Phantom Scanning Systems.
AB  - PURPOSE: There are many water-phantom scanning systems with advanced features to
      collect accurate commissioning data. However the intra- and inter-variability of
      commissioning data has not been reported which is attempted in this study.
      METHODS: Four vendors with modern water-phantom scanning systems; PTW, Sun
      Nuclear (SN), Standard Imaging (SI) and IBA were invited to an institution to
      demonstrate beam data collection. Each system was used to collect percent depth
      dose (PDD) and profiles several times in a day with their choice of detector for
      four different machines for photon and electron beam commissioning. This provided
      information on intra-variability. At the end, each vendor was allowed to setup
      and collect data on a single unit for inter-variability. All data were sent to a
      central location for analysis and evaluation. RESULTS: The depth dose and
      profiles for 2*2cm2 and 10*10cm2 fields were analyzed for intra- and inter
      variability. With repeated measurements, the intra-variability provided a
      detailed degree of fidelity of data collection. This was shown to be with (+/-
      0.1%) among all vendors. Ignoring data in buildup region and comparing with one
      system (PTW), the PDDs variability were slightly larger 0.02+/-0.17%, 0.14+/
      0.21%, 0.17+/-0.2%, for SI, SN and IBA, respectively. The profiles inter
      variability in central region were <0.1 %, however in penumbra up to +/- 4.8%were
      observed. The polarity effect was also noted up to 3% which was depth and
      detector dependent. CONCLUSIONS: Intra- and inter-variability among various
      scanning system are very small indicting that all modern systems if used properly
      could collect data within+/-0.2% accuracy. The selection of device should be
      based on institutional comfort and personal preference of software and hardware.
      This study provides unique opportunity to compare data among systems which is
      otherwise not possible.

PMID- 28517128
TI  - SU-E-T-136: Comparison of TomoScannerTM 2D Water Phantom versus IBA Helix for
      Tomotherapy Profile Measurements.
AB  - PURPOSE: To compare the differences in measured data using Tomotherapy's
      TomoScannerTM 2D Water Phantom versus IBA's Blue Phantom Helix taken during
      commissioning of the Tomotherapy HD unit. METHODS: IBA Helix was used with CC04
      ion chamber to measure Inline (jaw-size width), Crossline (40 cm width) and
      Percent Depth Dose (PDD). Data was analyzed using IBA Omni-Pro 7.3 software.
      Measurements were performed at 85 SSD for field sizes 5*40 cm2 , 2.5*40 cm2 , and
      1.0*40 cm2 . All field sizes were measured at 1.5 cm (nominal dmax), 5 cm, 10 cm
      and 15 cm depths. Scans were performed at a continuous speed setting of 0.5
      cm/sec. Setup and data measurements were performed twice on separate occasions
      for consistency and repeatability. Data measurements were normalized to 10 cm
      depth and compared to commissioning data taken from TomoScannerTM and
      Tomotherapy's Twinning Data. RESULTS: For all jaws, the profiles measured at 5
      cm, 10 cm, and 15 cm depth using IBA Helix matched the profiles of the
      TomoScannerTM data within 1%. Profile variance at 1.5 cm depth showed a deviation
      of up to 3%. For all jaws, the PDD comparisons displayed 3-5% deviation from the
      surface to 2 cm depth and within 1% deviation at 2 cm to 15 cm depth.
      Measurements performed using CC04 ion chamber versus A1SL ion chamber (used by
      Standard Imaging) showed data differences of less than 0.5%. CONCLUSIONS:
      Discrepancies in Tomotherapy beam profiles were observed between different water
      phantoms. Further investigation is required to determine the cause of variances
      between IBA and Tomotherapy data sets such as investigating geometrical
      differences between the water tanks and software dissimilarities in collecting
      and correcting raw data. It is recommended that independent commissioning data be
      taken when TomoScannerTM is not the clinical site's standard water phantom.

PMID- 28517129
TI  - SU-E-T-107: Uncertainty Estimate of a Practical EBT-2 Film Dosimetry Approach:
      Transpose-And-Scan Technique.
AB  - PURPOSE: To estimate the uncertainty of a practical EBT2 film dosimetry approach
      that has been established at our institution and used for routine patient
      specific plan verifications, particularly for SBRT and RapidArc, as well as
      planning system commissioning. Our technique is unique from other common
      dosimetry protocols with respect to calibration, irradiation and scanning.
      METHODS: Film dosimetry for patient-specific quality assurance of 29 patient
      plans were retrospectively reviewed. For each case, four films were irradiated;
      two for calibration and two for treatment plan. Each pair of two films were
      irradiated together in a phantom with one film transposed (rotated 180 degrees
      relative to the other) to compensate for asymmetric film response. After a
      minimum of 12 hrs post-irradiation, each film was scanned in four different
      orientations to mitigate non-uniform response of the scanner light and detector
      elements. The scanned 8 calibration and 8 plan images were averaged into one
      calibration and one plan film image, respectively. Each color channel of the
      calibration film was correlated to the reference dose matrix to produce a 3rd
      order polynomial calibration curve. Finally, each color channel of the plan film
      was converted to a dose map using the corresponding calibration curve. Average
      dose maps of the red and green channels were correlated to the treatment planning
      dose matrix, and the mean dose differences at the center of dose distributions
      (5*5mm2 area) as well as a gamma analysis were evaluated. RESULTS: The absolute
      dose differences were -0.8+/-1.7% (range=-4.5-3.0%). The gamma pass-rates
      (3%/3mm) were 94+/-7% (min.=74%). The pass rate increased to 99+/-3%(min.=87%)
      with the film scaled relatively to the plan doses. CONCLUSIONS: Based on a large
      number of cases, our approach appears to be robust to non-uniform film and
      scanner responses, and is shown to have an uncertainty (1SD) of less than 2% for
      absolute film dosimetry.

PMID- 28517130
TI  - SU-E-T-118: Characterization of EBT3 Films in Photon and Proton Beams.
AB  - PURPOSE: To measure the calibration curves of EBT3 dosimetry films in photon and
      proton beams and to quantify the related uncertainties from one beam type to
      another. METHODS: EBT3 Gafchromic films have similar properties than EBT2 with a
      symmetric construction and a matte polyester substrate to prevent Newton's ring
      artefacts. Films from a same batch were exposed in three different beam
      qualities, an Elekta SL25 6 MV photon beam, a 100 MeV 5*5cm2 proton beam
      delivered by pencil-beam scanning dedicated system from IBA and a 60 MeV fixed
      proton beam (2.5cm in diameter) at Clatterbridge Center for Oncology (CCO), UK.
      The films were read using an EPSON 10000 XL/PRO scanner. Film calibration curves
      were acquired for all modalities within a range of 0.05 to 20 Gy. Influence of
      increasing linear-energy transfer (LET) on film response was investigated by
      comparing dose measured by EBT3 to a silicon diode detector in depth for a fully
      modulated beam using the CCO beam line (homogeneous dose with distal end at 3.1cm
      in water). A comprehensive uncertainty budget (reproducibility, uniformity'|) was
      estimated on films irradiated by Elekta SL25. RESULTS: The main source of
      uncertainty was the non-uniformity of the scanner response. By placing all the
      irradiated films at the center of the scanner, the uncertainty could be reduced
      from 5.8% to 1.9% (1 sigma). For all beams and energies, the calibration curves
      were matched within uncertainties. Along the fully-modulated depth dose curve,
      diode and EBT3 measurement were in a 4% agreement point-to-point, indicating
      films weak dependence with LET. CONCLUSIONS: The weak influence of LET, beam type
      and energy on film response as well as its small uncertainty make EBT3 suitable
      for relative dosimetry and a promising candidate for measuring correction factors
      (quality, recombination,'|) for reference dosimetry with ion chambers of non
      standard beams (e.g pencil-beam scanning proton-therapy). a?oeThis work is
      supported by the Walloon Region under the project name InVivoIGT, convention
      number 1017266.a?.

PMID- 28517131
TI  - SU-E-T-90: Investigation of Different Bleaching Wavelengths on the Absorbed-Dose
      Sensitivity of NanoDot OSLDs Exposed to 6 MV X-Ray Beams.
AB  - PURPOSE: To determine the effect of different bleaching wavelengths on the
      luminescence response of Al2 O3 :C optically stimulated luminescence detectors
      (OSLDs) exposed to accumulated doses of 6 MV photon beams. METHODS: OSLDs of the
      nanoDot type were used and readout with a microStar InLight reader. To determine
      the effect of different bleaching wavelengths on the luminescence response of
      nanoDot OSLDs, we optically reset (bleached) the OSLDs with 26 W fluorescent
      lamps in two modes: (i) directly under the lamps for 10, 120 and 600 min; and
      (ii) with a long pass filter for 55, 600 and 2400 min. The long pass filter
      blocks wavelengths below 495 nm, hence the longer bleaching duration to attain
      equivalent OSL signals as bleaching directly under the lamps. Changes in the
      sensitivity of the nanoDot OSLDs were determined for an irradiation-readout
      bleaching-readout cycle, after irradiations with 1 and 10 Gy dose fractions.
      RESULTS: The nanoDot OSLDs presented a linear response to dose up to 2 Gy and
      supra-linear response afterwards. They produced different OSL signal loss and
      fading behaviors for doses of 1 and 10 Gy. OSLDs bleached for 120 min and 600 min
      without and with the filter in 1 Gy fractions, did not exhibit any significant
      change in sensitivity over an accumulated dose of 7 Gy. The OSLDs exposed with 10
      Gy fractions exhibited a small under-response when bleached with filter, and an
      over-response when bleached directly without filter. CONCLUSIONS: The nanoDot
      OSLDs may be reused without a significant sensitivity change for accumulated
      doses below 7 Gy. However, for accumulated doses beyond 10 Gy, nanoDot OSLDs show
      significant sensitivity change and hence, need to be recalibrated for reuse. We
      also concluded that the light spectrum used to reset the OSLDs has an influence
      on the sensitivity of the detectors. Natural Sciences and Engineering Research
      Council of Canada.

PMID- 28517132
TI  - SU-E-T-129: Rescaling of IMRT Verification Deviations from Detector Arrays into
      the Patient.
AB  - PURPOSE: To discuss a method of "rescaling" failures detected in a Gamma-Index
      analysis with detector arrays into the patient as a re-evaluation method in IMRT
      verifications. METHODS: In a homogeneous phantom, plane signals measured with
      ionisation chamber arrays during IMRT field-by-field verifications can be
      understood as resulting from the convolution of the incident photon fluence with
      two spatially invariant kernels (dose deposition in the measurement plane and
      spatial detector response). In principle, Gamma-Index deviations between planned
      and the measured plane signal profiles can therefore be "back-projected" into a
      deviation of the photon fluence profile from the planned one which can be
      "forward-projected" as a dose deviation at test points in the patient. Assuming
      this model for each field under investigation, all Gamma-Index failures in a
      certain array region can thus be "rescaled" as deviations of the patient dose and
      evaluated by with patient related tolerances. The method is evaluated in the
      prostate and H&N region by use of the 2D-ARRAY729 and VeriSoft5.0. The software
      offers the possibility to project the position of the ionization chambers onto
      the patient's CT. Thereby, the field specific analysis of deviations between
      measurements and plan is supported by suitable imaging procedures. Simulated
      Gamma-Index failures (3mm/3%) have been evaluated according to the method
      described above and compared with direct dose calculations. RESULTS: The degree
      of consistency between relative dose deviations predicted from 2D-ARRAY
      evaluations and corresponding relative dose deviations calculated within the
      patient is found to be in an acceptable range. The applicability in regions of
      inhomogeneity boundaries (air-tissue) and out of field regions was not included
      in this study and will be analyzed in the future. CONCLUSIONS: In combination
      with the described visualization tools, the method offers the possibility to re
      evaluate the dose deviations inside the patient when Gamma-Index failures have
      been detected with 2D-arrays.

PMID- 28517133
TI  - SU-E-T-100: How to Improve the Dose Accuracy for Gantry Angle Dependent Patient
      Specific IMRT QA Using 2D Ion Chamber Array with Octavius Phantom.
AB  - PURPOSE: To determine the cross calibration factors which can predict more
      accurate dose distribution for fixed beam IMRT QA using Octavius phantom.
      METHODS: The ion chamber based Octavius 2D-array detector (PTW, Freiburg,
      Germany) is a step in the right direction to measure the absolute dose and dose
      distribution for patient specific IMRT QA. However, the directional dependency of
      this detector made it less than desirable for angle dependent IMRT QA. We
      evaluated the new Octavius system (PTW, Freiburg, Germany) for angle dependent
      IMRT QA which compensates the response due to directional dependency. The system
      is designed for full arc VMAT QA, but does not always work for the discrete angle
      IMRT QA due to non-averaging of errors caused by directional dependence of
      detectors. The proposed method uses correction factors for each gantry angle. The
      dose for a 10cm * 10cm open field for each gantry angle was calculated by
      treatment planning system and measured using the Octavius phantom. The correction
      factors were determined at each gantry angle and the dose distribution was
      renormalized at each angle using correction factors. RESULTS: The discrepancy
      between measured and planned dose per monitor unit depended on the gantry angle
      and were in the range of +-4% using the PTW method. Using our method, uncertainty
      due to the detector angle dependency was eliminated. CONCLUSIONS: The new method
      removes the angle dependency of ion chamber based 2D array detector for the fixed
      beam IMRT QA. It provides fast, accurate and more realistic results for angle
      dependent IMRT QA.

PMID- 28517134
TI  - SU-E-T-140: A Study of Gafchromic EBT-3 Film for the Dosimetry of X-Ray Beams.
AB  - PURPOSE: To evaluate the dosimetric characteristics of the newly released
      Gafchromic EBT3 film and determine its suitability for surface dose measurements
      of 6MV x-ray beams. METHODS: Sheets of Gafchromic EBT3 film (Ashland Specialty
      Ingredients, NJ, USA) were cut into rectangular samples according to the
      providing user guide. All irradiations were performed using the 6MV x-ray beam on
      a Novalis linear accelerator (Varian Medical Systems). Optical density (OD) -
      dose calibration curves were determined by irradiating different film samples
      with doses in the range from 0 to 3 Gy and were read out using an X-rite
      densitometer using multiple readings over the samples surface. The OD was
      measured at different times after irradiation in order to determine stability of
      the film development. Surface doses were determined by placing film samples on
      the surface of a Virtual Water phantom for a range of field sizes from 3*3 to
      20*20 cm2 . RESULTS: Sheets of Gafchromic EBT3 film (Ashland Specialty
      Ingredients, NJ, USA) were cut into rectangular samples according to the
      providing user guide. All irradiations were performed using the 6MV x-ray beam on
      a Novalis linear accelerator (Varian Medical Systems). Optical density (OD) -
      dose calibration curves were determined by irradiating different film samples
      with doses in the range from 0 to 3 Gy and were read out using an X-rite
      densitometer using multiple readings over the samples surface. The OD was
      measured at different times after irradiation in order to determine stability of
      the film development. Surface doses were determined by placing film samples on
      the surface of a Virtual Water phantom for a range of field sizes from 3*3 to
      20*20 cm2 . CONCLUSIONS: The Gafchromic EBT-3 film has shown to be a stable and
      useful dosimeter for megavoltage x-ray beams including the determination of
      surface dose.

PMID- 28517136
TI  - SU-E-T-143: Effect of Physical and Virtual Wedges on the Surface Dose at Various
      SSD for 6 and 15 MV Photon Beam.
AB  - PURPOSE: To study the effect of the virtual wedge and physical wedge filters on
      the surface and build-up region doses for 6 and 15MV high-energy photon beams for
      different field sizes and various source to surface distance(SSD). METHODS: The
      measurements were made in water equivalent (PMMA) solid phantom in the build-up
      region at various SSD for various field sizes using virtual and physical wedge
      filters having different angles. A parallel-plate ion chamber (Markus) was used
      to measure the percent depth doses at surface and buildup region. Plane parallel
      ion chamber with fixed plate separation on the surface and buildup region would
      perturbate the dose measured, to get the proper dose over response correction
      factor was used. RESULTS: The percentage depth dose at surface (PDD0) increased
      as the field size increased for open, virtual, and physical wedged beams. For
      open, 30 degree physical, and virtual wedged beams, the surface doses were found
      to be 15.4%, 11.2%, and 15.2% with 6-MV photons and 11.2%, 9.4%, 11.2% with 15-MV
      photons, respectively, at 10 * 10 cm2 field size at 100cm SSD.As SSD increases
      percentage depth dose at surface (PDD0) decreases for open,physical and virtual
      wedge field. CONCLUSIONS: Percentage depth dose at surface (PDD0) of virtual
      wedged beams were similar to those of open beams. PDD0 of physical wedged beams
      were lower than those of open and virtual wedged beams. Surface doses for both PW
      and VW increases with field size and small increase in surface dose for both PW
      and VW fields as wedge angle increases especially for large fields.

PMID- 28517135
TI  - SU-E-T-111: Single Line Multi-Detector Scintillation Dosimetry: Demonstration of
      Feasibility.
AB  - PURPOSE: Obtain feasibility data on the use of multiple scintillators on a single
      optical line for dose measurements. METHODS: A CsI (Tl doped) crystal and a
      plastic (Rexon Inc, Rp-408) scintillator detectors, both transparent, were
      attached to the end of a fiberoptic line and connected to an Ocean Optics USB
      2000 spectrometer. After baseline spectra, spectra with the two scintillators
      adjacent to each other and then separated by a 7.6 cm plexiglass spacer were
      obtained. Irradiations were performed using 6 MV X-ray beam from a Varian EX
      linear accelerator. Utilizing the baseline spectra the dose received by each
      scintillator were calculated from the measured spectral peaks of the linear
      scintillator assemblies. Linearity tests were performed by varying dose and the
      dose rate in a homogeneous radiation field covering both scintillators. Unequal
      doses were delivered to the scintillator by gradually closing the collimator from
      one direction, blocking one detector at a time. Doses to the scintillators were
      modulated by different amount of solid water placed over the two detectors, as
      well. RESULTS: Measured scintillation spectra agreed with the published spectra.
      The spectra did not change with depth in the phantom. The multi-scintillator
      system response was strictly linear between 1.67 and 40 MUs, (approx. 1.3 to 31
      cGy) and dose rate independent between 100 to 600 MU/min. The profile curves
      obtained by closing the collimator agreed with qualitatively expected curves.
      Doses measured under different phantom thicknesses were in good agreement with
      ion chamber measurements on the same locations (+/- 3%). The linearity and dose
      rate independence allow absolute dose calibration for given beam energies and
      scintillator arrangement. CONCLUSIONS: Multi-probe scintillation dosimetry along
      a single optical fiber is possible in therapeutic irradiation conditions. This is
      feasible by using signals from multiple select scintillators with distinct
      spectroscopic responses arranged along an optical fiber.

PMID- 28517137
TI  - SU-E-T-102: Evaluation of the Characteristics of TLD LiF:Mg.Ti-100 Powder: A
      Measure of Consistency between Multiple Batches of Powder.
AB  - PURPOSE: Analyze the characteristics of TLD LiF-100 powder between multiple LiF
      crystal batches. METHODS: The RPC used TLD LiF-100 encapsulated powder to verify
      the output for photon and electron beams for 4 to 23 MV X-ray beams and 6 to 23
      MeV electron beams, respectively, from the past 15 years. During that time
      period, the RPC commissioned more than 15 batches of TLD powder. Commissioning of
      each batch of powder encompassed determining the system sensitivity (dose
      response), linearity, energy and fading characteristics of each batch of powder
      to determine the correction factors for the calculation of dose. The system
      sensitivity is the signal/mg per unit known dose of 60Co for each reading
      session. Other correction factors account for the loss of signal (fading) between
      the irradiation and read dates, supralinearity of the dose response and energy
      differences as compared to the 60Co irradiated standards. RESULTS: More than 15
      batches of TLD were commissioned to determine correction factors for the
      calculation of dose. The correction for fading, a characteristic of the LiF
      crystal, varied by +/-1% between the multiple batches. The linearity correction,
      between 25 and 600cGy, normalized to 300cGy, showed a maximum variation of +/-3%
      between batches. The energy correction factors, as defined for the RPC beam
      output audit system varied within +/-1.7% (one std dev.) for the 15 batches. The
      system sensitivity is highly dependent on the LiF crystal grown for each batch,
      specific TLD reader and reading session conditions. The system sensitivity, while
      keeping the readers and reading sessions constant, varied by as much as 20%
      between batches. CONCLUSIONS: Each batch of LiF-100 TLD powder showed variability
      in their powder characteristics such that calculation of dose accurately, with
      minimal uncertainty, requires a new commissioning. Work supported by PHS CA010953
      awarded by NCI, DHHS.

PMID- 28517138
TI  - SU-E-T-113: Volume Effect Correction Factor KV for Small-Field Photon Dosimetry
      with Ionization Chambers.
AB  - PURPOSE: The volume effect of ionization chambers gives rise to a spatial
      averaging effect that can be expressed mathematically as the convolution of the
      true dose profile with the detector's response function. The latter has been
      shown to be best described by Gaussian distribution. Based on this knowledge, the
      volume effect correction factor kV is derived. METHODS: To derive kV, a sixth
      degree polynomial is fitted to the true dose profile: D(x) = a0 + a2*2 + a4*4 +
      a6*6. The measured dose profile M(x) is calculated as the convolution product of
      D(x) with a one-dimensional normalized Gauss function with standard deviation s.
      Therefore kV at the dose maximum has the value D(0)/M(0), which is a function of
      the coefficients a0,2,4,6 and the detector specific s. In the case where D(x) is
      unknown, kV can be derived analogously from M(x) so that M(x) = b0 + b2*2 + b4*4
      + b6*6, where kV can now be expressed as a function of the coefficients b0,2,4,6
      and s. RESULTS: The magnitudes of kV,lat and kV,long were calculated for 1 to 5
      cm dose profiles using measured s values, both in the lateral and the
      longitudinal directions, for a set of common ionization chambers. At field widths
      above 2 cm, the values of kV,lat fall below 1.01 for all the chambers evaluated,
      whereas it needs field widths above 4 cm to get all values of kV,long below 1.01.
      Since the detector's signal is integrated over the sensitive volume, the total kV
      can be calculated as kV,total = kV,lat . kV,long. CONCLUSIONS: In this work, a
      correction is developed to eliminate the volume effect of ionization chambers
      when they are positioned in the maxima of dose profiles, particularly for the
      performance of output factor measurements for the calibration of narrow photon
      beams.

PMID- 28517139
TI  - SU-E-T-124: A Modified Winston Lutz Test Enabling Beam to Laser Angle
      Measurements.
AB  - PURPOSE: To present a modified Winston-Lutz-Test procedure able to measure beam
      and laser angles. METHODS: Room lasers have not only to indicate the isocenter
      spot but should also be aligned to the central beam axis. Therefore a modified WL
      test, based on a cube phantom made of low density foam material was developed.
      The classical steel sphere in the center is surrounded by 8 additional smaller
      spheres located near the cube corners. Surface markers on the cube indicate the
      position of the spheres and are used for easy setup to the lasers. Measurements
      are made with a field size covering all spheres in the well known way, ideally
      with a gantry mounted EPID. Result is an image of in total 9 spheres that is
      influenced by the distances and incoming beam directions. An automated template
      based detection algorithm then searches the image for the spheres as well as for
      the outside field boundaries. Knowing the phantom geometry, it is now easy to
      calculate the following parameters: Position of center sphere and laser to
      central axis of the beam, beam angle to the orientation of the phantom and the
      distance of the cube to the radiation source. Calculation result s then can be
      used to correct the phantom position and orientation. A transfer device equipped
      with a finder sight then allows to set the lasers. RESULTS: Test measurements
      were taken at a Siemens Artiste. Here the detection accuracy for angles and
      positions was tested. For smaller angles the automated detection works quite well
      within an accuracy of around 0.1 degrees  (max error 0.2 degrees ). Position
      detection was below 1/10mm and showed clearly the effects of Gantry and
      collimator sag. CONCLUSIONS: This method detects both, positions and angles of
      laser and beam, enabling a higher precision laser setup.

PMID- 28517140
TI  - SU-E-T-96: Energy Dependence of the New GafChromic- EBT3 Film's Dose Response
      Curve.
AB  - PURPOSE: To study and compare the dose response curves of the new GafChromic EBT3
      film for megavoltage and kilovoltage x-ray beams, with different spatial
      resolution. METHODS: Two sets of EBT3 films (lot#A101711-02) were exposed to each
      x-ray beam (6MV, 15MV and 50kV) at 8 dose values (50-3200cGy). The megavoltage
      beams were calibrated per AAPM TG-51 protocol while the kilovoltage beam was
      calibrated following the TG-61 using an ionization chamber calibrated at NIST.
      Each film piece was scanned three consecutive times in the center of Epson
      10000XL flatbed scanner in transmission mode, landscape orientation, 48-bit color
      at two separate spatial resolutions of 75 and 300 dpi. The data were analyzed
      using ImageJ and, for each scanned image, a region of interest (ROI) of 2*2cm2 at
      the field center was selected to obtain the mean pixel value with its standard
      deviation in the ROI. For each energy, dose value and spatial resolution, the
      average netOD and its associated uncertainty were determined. The Student's t
      test was performed to evaluate the statistical differences between the netOD/dose
      values of the three energy modalities, with different color channels and spatial
      resolutions. RESULTS: The dose response curves for the three energy modalities
      were compared in three color channels with 75 and 300dpi. Weak energy dependence
      was found. For doses above 100cGy, no statistical differences were observed
      between 6 and 15MV beams, regardless of spatial resolution. However, statistical
      differences were observed between 50kV and the megavoltage beams. The degree of
      energy dependence (from MV to 50kV) was found to be function of color channel,
      dose level and spatial resolution. CONCLUSIONS: The dose response curves for
      GafChromic EBT3 films were found to be weakly dependent on the energy of the
      photon beams from 6MV to 50kV. The degree of energy dependence varies with color
      channel, dose and spatial resolution. GafChromic EBT3 films were supplied by
      Ashland Corp. This work was partially supported by DGAPA-UNAM grant IN102610 and
      Conacyt Mexico grant 127409.

PMID- 28517141
TI  - SU-E-T-135: Investigation of Commercial-Grade Flatbed Scanners and a Medical-
      Grade Scanner for Radiochromic EBT Film Dosimetry.
AB  - PURPOSE: To evaluate the characteristics of commercial-grade flatbed scanners and
      medical-grade scanners for radiochromic EBT film dosimetry. METHODS: Performance
      aspects of a Vidar Dosimetry Pro Advantage (Red), Epson 750 Pro, Microtek
      ArtixScan 1800f, and Microtek ScanMaker 8700 scanner for EBT2 Gafchromic film
      were evaluated in the categories of repeatability, maximum distinguishable
      optical density (OD) differentiation, OD variance, and dose curve
      characteristics. OD step film by Stouffer Industries containing 31 steps ranging
      from 0.05 to 3.62 OD was used. EBT films were irradiated with dose ranging from
      20 to 600 cGy in 6*6 cm2 field sizes and analyzed 24 hours later using RIT113 and
      Tomotherapy Film Analyzer software. Scans were performed in transmissive mode,
      landscape orientation, 16-bit image. The mean and standard deviation Analog to
      Digital (A/D) scanner value was measured by selecting a 3*3 mm2 uniform area in
      the central region of each OD step from a total of 20 scans performed over
      several weeks. Repeatability was determined from the variance of OD step 0.38.
      Maximum distinguishable OD was defined as the last OD step whose range of A/D
      values does not overlap with its neighboring step. RESULTS: Repeatability
      uncertainty ranged from 0.1% for Vidar to 4% for Epson. Average standard
      deviation of OD steps ranged from 0.21% for Vidar to 6.4% for ArtixScan 1800f.
      Maximum distinguishable optical density ranged from 3.38 for Vidar to 1.32 for
      ScanMaker 8700. A/D range of each OD step corresponds to a dose range. Dose
      ranges of OD steps varied from 1% for Vidar to 20% for ScanMaker 8700.
      CONCLUSIONS: The Vidar exhibited a dose curve that utilized a broader range of OD
      values than the other scanners. Vidar exhibited higher maximum distinguishable
      OD, smaller variance in repeatability, smaller A/D value deviation per OD step,
      and a shallower dose curve with respect to OD.

PMID- 28517142
TI  - SU-E-T-106: Evaluation of Sensitivity and Uniformity of New Radiochromic Film
      with Two Commercial Scanners.
AB  - PURPOSE: A newly introduced radiochromic film, the GAFCHROMIC EBT3, has been
      expected as much useful device for the IMRT dosimetry. The purpose of this study
      was to investigate the sensitivity and the uniformity of the films between an
      Epson ES-10000G flatbed scanner and a Vidar DosimetryPRO Advantage (Red) scanner.
      METHODS: Doses ranging from 1 cGy to 1600 cGy with 15-MV photon beam was
      irradiated to the film in a solid water phantom, respectively. All of the films
      were then digitized after irradiation using both two scanners. Sensitivities,
      local fluctuations of the film with two scanners were evaluated. Local
      fluctuations were defined as the relative (percent) standard deviation of the
      film response in ROIs (3 cmx3 cm). RESULTS: As to the Vidar scanner, the
      sensitivity of the film was higher for low dose range (below <400 cGy). While, as
      to the Epson scanner, the sensitivity using the red color channel was higher than
      others for low dose range. At high dose range (above >400 cGy), the green color
      channel had higher sensitivity than others. The Vidar scanner exhibited the lower
      local fluctuations than the Epson scanner for all dose ranges. For the Epson
      scanner, the red color channel had the lower local fluctuations than the green
      and blue color channel for all dose ranges. CONCLUSIONS: This study shows the
      characteristics of the new EBT3 films, in conjunction with the Epson ES-10000G
      flatbed scanner and the Vidar DosimetryPRO Advantage (Red) scanner.

PMID- 28517143
TI  - SU-E-T-117: A Point Densitometer Scanner for EBT2 Film Dosimetry.
AB  - PURPOSE: To create and characterize a device that can accurately and reproducibly
      digitize Gafchromic(R) EBT2 film for dosimetry. METHODS: We have constructed a
      point densitometer scanner that allows the acquisition of 1 dimensional optical
      density profiles of EBT2 dosimetry film at submillimeter resolution. An LED with
      peak output at 636nm collimated and focused with an aspheric lens was used as a
      light source. A large area photodiode was used as a detector. A custom
      transimpedence amplifier was developed to optimize the detector signal response
      for optical densities corresponding to a clinically relevant dose range (0 -
      3Gy). A custom motorized translational stage was developed allowing 1 dimensional
      scans and manual fine adjustment in the lateral direction. The entire scanner was
      contained in a light tight enclosure to eliminate the effects of ambient light.
      Dose profiles were generated from EBT2 films exposed uniformly to varying doses
      using a superficial unit with the films placed on top of a solid water phantom.
      Dose profiles were generated from the same films using a flatbed scanner (Epson
      10000XL) implementing two and three optical channel corrections for film
      inhomogeneity and the results were compared. RESULTS: Initial analysis of the
      point densitometer shows a beam FWHM of 0.7mm and position error of the
      translational stage at 0.02mm in the scan direction and 0.2mm in the lateral
      direction. Reproducibility of the scans has been shown to within 1%. Orientation
      dependence and measured dose homogeneity have been improved over corrected
      flatbed digitization techniques. CONCLUSIONS: Preliminary characterization of the
      point densitometer shows its potential as an improved quality assurance tool for
      EBT2 film dosimetry.

PMID- 28517144
TI  - SU-E-T-89: Characterization of Dental Restoration Material for Cs-137 Radiation
      Dosimetry.
AB  - PURPOSE: The purpose of this work is to characterize the radiation-induced
      thermoluminescence properties of a dental restoration material and to see if the
      material might be feasible for use in retrospective radiation dosimetry. METHODS:
      Retrospective, or accidental, dosimetry is the study of using nearby materials to
      measure radiation received by individuals. In this project we obtained samples of
      Ivoclar Vivadent e.max CAD material, a glass-ceramic used for making dental
      restorations such as full or partial crowns. The samples were machined into
      square chips .32 cm * .32 cm * .089 cm and annealed in the same furnace used by
      the dentist. The samples were exposed to a Cs-137 source using a PMMA source
      holder and then read in a Harshaw 3500 TLD reader. The samples were read without
      nitrogen gas flux using heating rates of 5 degrees C/s or 10 degrees C/s up to a
      maximum temperature of 400 degrees Celsius. The glow curves were analyzed using
      Systat PeakFIT peak-fitting software and Microsoft Excel spreadsheets. The
      authors gratefully thank Dr. Aaron Imdieke and the staff of River City Dental,
      St. Cloud, MN for the dental restoration materials and the use of their dental
      furnace. RESULTS: A sample subjected to a radiation exposure of .04 C/kg exhibits
      a glow curve with a prominent peak at approximately 140 degrees Celsius, which is
      well-modeled by the first order glow curve deconvolution formula developed by
      Kitis, Gomez-Ros, and Tuyn. The activation energy corresponding to this peak is
      approximately 1 eV. The thermoluminescent signal fades with time after exposure.
      CONCLUSIONS: Ivoclar Vivadent e.max CAD dental restoration material has the
      potential to be used as a material for retrospective Cs-137 radiation dosimetry.
      Future work could look at its thermoluminescent dosimetry properties in more
      detail and also at other dental restoration materials. The authors would like to
      thank Dr. Aaron Imdieke and the staff of River City Dental, St. Cloud, MN, for
      the donation of scrap dental restoration materials and the use of their dental
      furnace.

PMID- 28517145
TI  - SU-E-T-128: Dosimetric Characteristics of Gafchromic EBT3 Films for Megavoltage
      Photon and Proton Beams.
AB  - PURPOSE: Gafchromic film for quantitative analysis was renewed from EBT2 to EBT3
      film in November 2011. The purpose of this study is to investigate the relevant
      characteristics of EBT3 film for its application in dosimetric verification for
      IMRT/VMAT or proton therapy. METHOD: We investigated the characteristics of EBT3
      film with comparison of previous EBT2 film. The experiments in this study
      composed two categories. At first, the photo spectroscopy for the irradiated film
      was compared between EBT2 and EBT3. The film 1 day after the irradiation was
      analyzed by a photo spectrometer (SR520: JASCO Corporation, Japan). Secondly, we
      investigated several calibration curves which obtained by same batch. The films
      were calibrated by irradiation the films to 13 dose steps. The irradiated films
      were scanned by a flatbed scanner (ES-10000XL, Epson-Seiko Corporation, Japan).
      The difference on scan orientation was evaluated alternate portrait and landscape
      directions. The photon and proton beams were delivered from Clinac 21EX (Varian)
      and Mitsubishi machine, respectively. RESULTS: The peak absorption wavelength of
      EBT3 film and its response at all active range were basically same with that of
      EBT2 film. The peak wavelength of photo absorption in EBT3 was observed at 585
      and 634 nm. The fog optical density was increased due to the hazy matte polyester
      for active layer. However, there is no change the tendency of the calibration
      curve responding to megavoltage photon and proton beams. The scan orientation
      dependency of EBT3 film was observed with similar to EBT2 film. The optical
      density of portrait orientation was 10% higher than that of landscape
      orientation. CONCLUSION: The dosimetric characteristics of EBT3 film were
      basically same with EBT2 film. With regard to the matte polyester, the creation
      of Newton's rings during scanning procedure was reduced. However, the suitable
      scan protocol should be used for accurate film dosimetry.

PMID- 28517146
TI  - SU-E-T-99: Small Field Output Factor Measurement Using MAGIC Gel Dosimeter in 3T
      MRI.
AB  - PURPOSE: Small field dosimetry is very important because of radiation therapy
      techniques that use small fields such as IMRT, gamma and body radiosurgery,
      cyberknife and tomotherapy. We investigated use of a MAGIC (Methacrylic and
      Ascorbic acid in Gelatin Initiated by Copper) gel dosimeter to quantitatively
      measure small field output factors (OFs) for 6MV x rays. METHODS: In this work,
      MAGIC (Gelatin 9%; Methacrylic acid 4%; CuSO4 0.1mM; Ascorbic ascid 2mM; Glucose
      10%) gel phantoms were developed to measure the 6MV x-ray output factors for 1*1
      up to 10*10 cm2 square fields (Varian 2100C linear accelerator). For comparison,
      3 ion chambers (PTW:TN30013, Exradin A12, Capintec PR-05P), Gafchromic film
      (EBT2), and TLD (LiF-100) were used to measure the small field OFs under
      identical experimental conditions: 6cm depth (solid water), SAD=100cm, SSD =
      94cm, 6MV, 512 MUs per irradiation. Relative OFs were normalized to a reference
      field (10*10 cm2 @ SAD =100cm). MAGIC gel dosimeters were scanned in a 3T GE
      signa(r) EXCITETM clinical scanner using a Spin Echo pulse sequence for dose
      distribution readout (pixel size = 0.4mm, slice thickness 3mm, TR = 4000ms, TE =
      10ms and 110ms, respectively). Gel dose distributions were then calculated using
      custom Matlab code. RESULTS: 6MV x-ray OFs versus field size for all detectors
      were graphically compared. The MAGIC polymer gel dosimeter OF for a 1*1 cm2 field
      is 0.612 (+/- 5%), approximately 2% different from the OFs measured using small
      volume dosimeters (TLD, EBT2 film and the Capintec PR-05P ion chamber). Larger
      ion chamber (PTW:TN30013 and Exradin A12, both ~ 0.6cc) OFs were low (OF = 0.26
      for 1*1cm2 ) due to nonequilibrium and partial volume conditions. CONCLUSIONS:
      MAGIC gel dosimeter with 3T MRI scanner as a read-out makes it an ideal tool for
      small field dosimetry.

PMID- 28517147
TI  - SU-E-T-139: Feasibility Study of Glass Dosimeter for in Vivo Measurement:
      Dosimetric Characterization and Clinical Application in Proton Beams.
AB  - PURPOSE: To evaluate the suitability of the GD-301 glass dosimeter for use in in
      vivo dose verification in proton therapy. METHODS: The glass dosimeter was
      analyzed for its dosimetric characteristic in proton beam. Dosimeters were
      calibrated in a water phantom using a stair-like holder specially designed for
      this study. To determine the accuracy of the glass dosimeter in proton dose
      measurements, we compared the glass dosimeter and TLD dose measurements of plan
      delivery using a cylindrical phantom. We investigated the feasibility of the
      glass dosimeter for the measurement of dose distributions near the superficial
      region for proton therapy plans with a varying separation between the target
      volume and the surface of 6 patients. RESULTS: Uniformity was within 1.5%. The
      dose-response has a good linear. Dose-rate, fading, and energy dependence were
      found to be within 3%. The beam profile measured using the glass dosimeter was in
      good agreement with the profile obtained from the ionization chamber. Depth-dose
      distributions in non-modulated and modulated proton beams obtained with the glass
      dosimeter were estimated to be within 3%, which was lower than those with the
      ionization chamber. In the phantom study, the difference of isocenter dose
      between the delivery dose calculated by the Eclipse and that of the measured by
      the glass dosimeter was within 5%. In vivo dosimetry of patients, given the
      results of the glass dosimeter and TLD measurements, calculated doses on the
      surface of the patient are typically overestimated between 4% and 16%.
      CONCLUSIONS: As such, it is recommended that bolus be added for these clinical
      cases. We also believe that the glass dosimeter has considerable potential to be
      used for in vivo patient proton dosimetry.

PMID- 28517148
TI  - SU-E-T-110: Small Electron Field Surface Dosimetry Using Solid State Detectors.
AB  - PURPOSE: Solid state detectors from two independent systems have shown similar
      over-responses to small electron fields used for treatment of surface lesions. We
      propose to evaluate the accuracy of solid state detector systems for highly
      blocked electron fields as a method for clinical dosimetry and determine the
      cause for any deviations from expected dose-delivery calculations. METHODS: A QED
      Diode detector system and a Best-Medical MOSFET dosimeter system were used to
      measure relative output factors (ROF's) for a range of blocked electron fields
      with 3 different electron energies. Measurements were taken on the surface of a
      Solid-Water phantom as well as under varying thicknesses of bolus (surface to
      dmax) to determine the extent of this effect with increasing depth. Measurements
      were compared with expected results obtained during machine commissioning with an
      A-14 micro-ionization chamber. RESULTS: Field sizes larger than 4*4 cm2 showed
      little significant deviation from expected output factor values. However, fields
      smaller than this threshold showed as much as a 30% over-response of the solid
      state detectors compared to ion chamber measurements on the surface. This
      deviation was consistent over multiple measurements using both systems. The
      degree of over-response is both energy and effective field size dependent. As the
      effective depth of measurement increases, the relative differences in responses
      decrease and eventually converge. CONCLUSIONS: Surface dosimetry using solid
      state detectors is a straightforward method of verifying dosimetric calculations.
      Care must be taken when using these systems for surface dosimetry with highly
      blocked fields as their non-tissue equivalence makes these detectors overly
      sensitive to low-energy scattered electrons and bremsstrahlung photons produced
      from the block edge. Measurements taken near dmax will not show a significant
      deviation from the actual dose and do not need to account for this effect.

PMID- 28517149
TI  - SU-E-T-121: Investigating the Optimal Scanning Resolution for Radiochromic EBT-2
      Films Using an Epson 10000XL Flatbed Scanner.
AB  - PURPOSE: The purpose of this work is to determine the optimal scanner resolution
      of an Epson 10000XL scanner for the analysis of radiochromic EBT-2 films. Using
      Fourier analysis and the Nyquist-Shanon sampling theory, the highest frequency
      component required to sufficiently reproduce a previously measured step dose
      profile was investigated. METHODS: A setup was created, in which one half of a
      6*6cm2 EBT-2 film was shielded on exposure using a 15*5*10cm3 lead block to
      obtain sharp step dose profiles. The film itself was placed between two 6cm RW3
      stacks on top of which the lead block was placed. Using a Siemens Primus linear
      accelerator operating at 6/15MV nominal energies, the setup was exposed to 400MUs
      at 6MV and 500MUs at 15MV respectively. Preliminary investigations were performed
      without RW3 between the lead and film. Initial image acquisition was performed at
      600dpi to minimize information loss. Using the average of five line profiles, a
      uniformity correction algorithm provided by the manufacturer was implemented
      prior to the Fast Fourier Transform (FFT) operation. In an iterative process, all
      frequency components above a cut-off frequency wcut were successively removed and
      the original image reconstructed with the inverse FFT operation. The goodness of
      fit was evaluated by comparing the change in penumbra width on image
      reconstruction. RESULTS: The minimum scanning resolution required to analyze the
      step dose profiles created without build-up material was 52dpi for 6MV and 30dpi
      for 15MV. By adding build-up material, in the areas of secondary electron
      equilibrium the required resolution reduces to 12dpi for 6MV and 8dpi for 15MV.
      CONCLUSIONS: For sufficient image reproduction within any information loss,
      resolutions as low as 52dpi at 6MV and 30dpi at 15MV are sufficient for
      evaluating EBT-2 films. This is in compliance with 50dpi recommended by the
      manufacturer.

PMID- 28517150
TI  - SU-E-T-142: Evaluation of the Energy Dependence of Gafchromic EBT3 Film for
      Electron Beams.
AB  - PURPOSE: To evaluate the energy dependence of Gafchromic EBT3 film for
      establishing a quality assurance method of bolus electron conformal radiotherapy.
      METHODS: We irradiated electron beam to EBT3 films, which were set in the water
      tank. The linear accelerator used was Varian Clinac 21EX. The energy of electron
      beams were 9 and 12 MeV. The irradiated field size was 10*10 cm2 and the source
      to surface distance was 100 cm. The depths of measurement were 22 (depth of dose
      maximum; dmax), 31, and 37 mm for 9 MeV and 28 (dmax), 43, and 50 mm for 12 MeV.
      The irradiated doses were 25, 50, 75, 100, 150, 200, and 300 cGy. EBT3 films were
      readout with a flat-bed scanner 48 hours after irradiation, and the optical
      density (OD) curve was obtained for each beam energy and depth. The OD curves
      were approximated by a third-order polynomial. The doses were evaluated at netOD
      0.1 and 0.3 from the approximated curves. RESULTS: The differences of the
      evaluated doses from those for 9 MeV at 22 mm depth were from 2 to 14 % for
      netOD=0.1, and from 1 to 13 % for netOD=0.3, respectively. The netOD curves of
      dmax for both energies showed good agreement, while large discrepancy was found
      in the deeper depths. CONCLUSIONS: The dependence of dose response of EBT3 film
      on electron beam energy was small at dmax, while it increased at deeper depth in
      the present study. It can be considered that the discrepancy was caused by setup
      error because dose gradient was steeper at the deeper region. In future work, we
      will perform more precise measurement with a solid phantom to evaluate the energy
      dependence of EBT3 film.

PMID- 28517151
TI  - SU-E-T-112: Experimental Characterization of a Novel Thermal Reservoir for
      Consistent and Accurate Annealing of High-Sensitivity TLDs.
AB  - PURPOSE: To develop and characterize a novel thermal reservoir for consistent and
      accurate annealing of high-sensitivity thermoluminescence dosimeters (TLD-100H)
      for dosimetry of brachytherapy sources. METHODS: The sensitivity of TLD-100H is
      about 18 times that of TLD-100 which has clear advantages in for interstitial
      brachytherapy sources. However, the TLD-100H requires a short high temperature
      annealing cycle (15 min.) and opening and closing the oven door causes
      significant temperature fluctuations leading to unreliable measurements. A new
      thermal reservoir made of aluminum alloy was developed to provide stable
      temperature environment in a standard hot air oven. The thermal reservoir
      consisted of a 20 cm * 20 cm * 8 cm Al block with a machine-milled chamber in the
      middle to house the aluminum TLD holding tray. The thermal reservoir was placed
      inside the oven until it reaches thermal equilibrium with oven chamber. The
      temperatures of the oven chamber, heat reservoir, and TLD holding tray were
      monitored by two independent thermo-couples which interfaced digitally to a
      control computer. A LabView interface was written for monitoring and recording
      the temperatures in TLD holding tray, the thermal reservoir, and oven chamber.
      The temperature profiles were measured as a function of oven-door open duration.
      The settings for oven chamber temperature and oven door open-close duration were
      optimized to achieve a stable temperature of 240 0C in the TLD holding tray.
      Complete temperature profiles of the TLD annealing tray over the entire annealing
      process were obtained. RESULTS: A LabView interface was written for monitoring
      and recording the temperatures in TLD holding The use of the thermal reservoir
      has significantly reduced the temperature fluctuations caused by the opening of
      oven door when inserting the TLD holding tray into the oven chamber. It has
      enabled consistent annealing of high-sensitivity TLDs. CONCLUSIONS: A
      comprehensive characterization of a custom-built novel thermal reservoir for
      annealing high-sensitivity TLD has been carried out. It enabled consistent and
      accurate annealing of high- sensitivity TLDs which could significantly improve
      the efficiency of brachytherapy source characterizations. Supported in part by
      NIH grant R01-CA134627.

PMID- 28517152
TI  - SU-E-T-123: Understanding the Meaning of IMRT QA Passing Rates with a 2D Diode
      Array.
AB  - PURPOSE: A lower than ideal tolerance limit is used in intensity-modulated
      radiation therapy quality assurance (IMRT QA) with a 2D diode array due to
      passing rate fluctuations. The objective is to identify patterns in the passing
      rates to predict sources of uncertainty that can affect treatment delivery, for
      example, the need to re-calibrate the multileaf collimator when the passing rates
      start to decrease. METHODS: Five complex clinical prostate IMRT plans were
      evaluated with a 2D diode array. The QA for each plan was repeated five times
      during one and a half month period. One of the plans was randomly selected and
      repeated the same day five consecutive times. The planar doses calculated by the
      treatment planning system were compared to the measurements of the 2D diode
      array. The individual passing rates per beam per plan were compared. RESULTS: The
      average passing rate for each plan ranged from 94% to 97%. While the average
      percent difference of this ranged between -7.67% to 17.61%. Additionally, the
      minimum and maximum standard deviation among all beams was 0.13% and 9.63%
      respectively. We also compared the standard deviation of a plan QA repeated
      during different days versus a plan QA repeated during the same day. For the
      former the highest standard deviation was 6.05 % while for the later 0.21%. We
      noticed that the largest discrepancy between the passing rates was for angles at
      around 155 degrees  and 205 degrees . CONCLUSION: These results show some
      inconsistency in the IMRT QA passing rates from one day to the next. Moreover,
      lower passing rates for a specific angle like the ones shown here can represent
      possible mechanical or tuning problems with the linear accelerator at these
      specific locations. Early identification of these sources of uncertainty can
      greatly improve the precision of the treatment delivery.

PMID- 28517153
TI  - SU-E-T-95: Investigation of 3D Dosimetry for an Anthropomorphic Spine Phantom.
AB  - PURPOSE: To evaluate 3D dosimetry for a spinal cord treatment plan delivery using
      the Radiological Physics Center's (RPC) anthropomorphic spine phantom. METHODS:
      The RPC's spine phantom currently uses radiochromic film and thermoluminescent
      dosimeters (TLD) to evaluate spinal metastases treatments. A second dosimetry
      insert for the phantom was created to hold a PRESAGE(r) 3D dosimeter which
      matched the location of the TLD and film in the original insert. The phantom was
      CT imaged with each insert and an IMRT treatment plan was developed. The IMRT
      plan was delivered to the phantom twice; once with each insert. The film and
      PRESAGE(r) were scanned on a CCD microdensitometer and optical-CT system,
      reconstructed to a 2 mm slice width, respectively. The measured dose
      distributions were compared to the treatment plan calculated dose distribution
      using RPC in-house developed software or the Computational Environment for
      Radiotherapy Research (CERR). Film and PRESAGE(r) dose profiles were taken across
      several planes and compared for agreement. The distance to agreement (DTA)
      between the measured data and treatment plan, within the high dose gradient
      region, was quantified. RESULTS: The PRESAGE(r) and plan dose profiles agreed to
      within 2and 1 mm in the AP and SI directions, respectively. The film and plan
      also agreed to within 2 mm across all profiles. CONCLUSIONS: The PRESAGE(r) 3D
      dosimeter, based on these preliminary data, shows potential as a dosimeter for
      the RPC's phantom irradiation studies. Future work will add markers to the
      PRESAGE(r) insert to allow for a reproducible registration in CERR and a an
      optical-CT system, reconstructed to a 2 mm slice width dose calibration protocol
      will be created. CA 100835.

PMID- 28517154
TI  - SU-E-T-134: Patient Specific Quality Assurance of RapidArc Pre Treatment Plans
      Using Semiflex 0.125 Cc Ionization Chamber.
AB  - PURPOSE: To evaluate the Patient specific pre-treatment quality assurance for
      hundred RapidArc plans using semiflex (0.125cc) ionization chambers. METHODS:
      Absolute point dose were measured for head and neck, thorax and abdomen cases
      using semiflex (0.125 cc) ionization chamber. Verification plan was created for
      each treatment plan in eclipse 8.6 treatment planning system with the semiflex
      ionization chamber and the octavius phantom. Measurements were performed on a
      Varian Clinac2100C/D linear accelerator equipped with a millennium 120 leaf
      collimator. All the results were compared with the fluence measurements using 2D
      Seven29 ion chamber array combined with octavius phantom. RESULTS: Positive
      absolute mean dose variation of 0.56 % was observed with thorax cases with a
      standard deviation (SD) of +/- 1.13 between the plans with a range of -1.78% to
      2.70%. Negative percentage dose errors were found with head and neck and abdomen
      cases, with a mean variation of -0.43 % (SD +/- 1.50), (range -3.25 % to 2.85 %)
      and -0.35 % (SD +/- 1.48), (range -3.10 % to 2.65 %) for head and neck and
      abdomen cases respectively. Relative dose measurements with 2D array agreed well
      with the TPS calculate for all the cases. The maximum percentage value failed in
      gamma analysis was found to be 4.95, 4.75, and 4.88 for head and neck, thorax,
      and abdomen cases respectively. In all the cases analysed the percentage dose
      points failed the gamma criteria was less than 5%. CONCLUSIONS: On the basis of
      the studies performed it can be concluded that the semiflex ionization chamber
      having a volume of 0.125cc can be used efficiently for measuring the pre
      treatment quality assurance of RapidArc plans for all the sites. The results
      provide an overall accuracy when compared to fluence measurement done using 2D
      array seven29.

PMID- 28517155
TI  - SU-E-T-105: The LET Dependence of Liquid Ionization Chambers (LICs) in High-LET
      Beams.
AB  - PURPOSE: LICs are novel detectors for radiotherapy: the higher density of the
      medium allows to build them with a smaller sensitive volume, making them
      appealing in particle therapy. With RBE varying along the depth dose curve (DDC)
      and with the rising interest in dose/LET-painting, verifying the LET is becoming
      more important. Nevertheless, while the LET distributions for different ionizing
      particles have been calculated, they have never been directly measured in
      realistic therapeutic beams. Our interest in LICs is based on the
      characterization of the beam quality in terms of LET. It has been shown in
      earlier works that the extrapolation of the linear portion of the voltage curve
      yields an intercept with the x-axis that depends on LET. The quantitative
      establishment of this method, however, depends on how accurately recombination
      effects are taken into account. METHODS: Due to the higher density of charge
      carriers produced in the liquid, LICs have high recombination effects: general
      recombination effects, involving pairs belonging to different tracks (dose rate
      dependent), and initial recombination between ion-electron pairs belonging to the
      same incident particle event (LET dependent). To perform this study we propose a
      two-dimensional array of LICs, composed by a 16*8 matrix of 2*2 mm2 pixels, which
      gives a fine spatial resolution on the plane. RESULTS: Voltage curves have been
      measured for proton, carbon and oxygen beams available at the HIT facility in
      Heidelberg for different energies and dose rates. After correcting the curves for
      general recombination losses using the Three Voltage Method, we have indications
      of dose rate independence, indicating successful correction. CONCLUSIONS: Further
      investigations are foreseen to quantify the LET dependence along the DDC, where
      different LET values are expected. A comparison with simulated dose averaged LET
      values will give quantitative information about 2D LET distributions for
      different beam species.

PMID- 28517156
TI  - SU-E-T-116: The Water Equivalence of Organic Liquid Scintillators for Proton
      Dosimetry.
AB  - PURPOSE: Organic liquid scintillators are currently under investigation for use
      in proton dosimetry. The purpose of this work is to evaluate the water
      equivalence of these materials as a preliminary step to identify scintillators
      that are well-suited to this purpose. METHODS: Stopping powers were calculated
      for 0.001-1000 MeV protons in water, polystyrene, and two organic liquid
      scintillators: BC-531 and OptiPhase 'Hi-Safe' 3 at 0%, 25%, and 50%
      concentrations of water. Angular scatter was quantified by theta0, a
      characteristic multiple Coulomb scattering angle analogous to the standard
      deviation of a Gaussian distribution of proton angles relative to the incident
      beam axis. Theta0 was calculated as a function of depth over the range of 200 MeV
      protons in these materials. RESULTS: Collisional stopping power in BC-531 ranged
      from +44% to +1% ofthat in water. It remained within 6% from 2-600 MeV. OptiPhase
      ranged from +24% to -2%, with smaller deviations at increased water
      concentrations. At all concentrations, OptiPhase showed smaller deviations than
      polystyrene and BC-531 and remained within 1% of water from 2-600 MeV.Theta0 was
      very similar for all materials, with deviations from water of 5 milliradians or
      less over the majority of the proton range. BC-531 showed deviations of 10
      milliradians or more in the last few millimeters of the range. OptiPhase showed
      smaller deviations than BC-531 or polystyrene, and these deviations decreased
      with increasing water concentration. CONCLUSIONS: OptiPhase was found to be more
      water equivalent than BC-531 or polystyrene in stopping power and angular
      scatter, and increased water concentration improved both quantities. Large
      deviations in stopping power were only found below 2 MeV for any material, where
      proton range is less than 0.1 millimeter. The deviations from water found in
      angular scatter were less significant, and probably too small to affect
      measurement.

PMID- 28517157
TI  - SU-E-T-88: Evaluating Gantry Sag on Linear Accelerators and Introducing an MLC
      Based Compensation Strategy.
AB  - PURPOSE: Gantry sag is one of the well-known sources of mechanical imperfections
      that compromise the spatial accuracy of radiation dose delivery. This study aims
      to quantify the gantry sag on multiple linacs and to investigate a multiple leaf
      collimator (MLC)-base strategy to compensate for gantry sag. METHODS: We used the
      Winston-Lutz method to measure the gantry sag on three Varian linacs. A ball
      bearing phantom was imaged with a square radiation field during gantry rotation.
      The images were analyzed to derive the radiation isocenter and subsequently the
      gantry sag, that is, the superior-inferior wobble of the radiation field center
      from the radiation isocenter as a function of gantry angle. Compensation for
      gantry sag was attempted by offsetting the MLC leaves at 90-degree collimator
      angle. The amount of offset was the opposite of measured gantry sag, which was
      gantry angle-specific. RESULTS: Gantry sag was reproducible within a six-month
      period. On the three linacs, the maximum gantry sag was found to vary from 0.7 mm
      to 1.0 mm, depending on the linac and the collimator angle. The radiation field
      center moved inferiorly, or away from the gantry, when the gantry was rotated
      from 0 to 180 degrees. Comparison of gantry sag at 0- and 90-degree collimator
      angles showed that the uncertainty in MLC leaf positions did not increase the
      gantry sag. Instead, gantry sag was caused primarily by nonideal gantry rotation.
      After the MLC compensation was applied, the maximum gantry sag was reduced to
      less than 0.2 mm. CONCLUSIONS: The results indicated that gantry sag on a linac
      can be quantitatively measured with sub-millimeter precision, using a simple ball
      bearing phantom and the electronic portal imaging device. Reduction of gantry sag
      is feasible by applying a gantry angle-specific correction to MLC leaf positions
      at 90 degree collimator angle.

PMID- 28517158
TI  - SU-E-T-127: Feasibility Study for Using a 2D Array Detector for All Beam
      Measurements in Monthly Quality Assurance Procedure for a Uniform Scanning Proton
      Therapy System.
AB  - PURPOSE: To develop a more efficient monthly quality assurance (QA) process by
      utilizing one detector with multiple setups instead of multiple detectors with
      multiple setups. METHOD: The Sun Nuclear IC Profiler was used to measure machine
      output, transverse profiles, and depth-dose profiles. The IC Profiler contains
      251 ionization chambers aligned in the X, Y, and diagonal axes, and was designed
      to measure machine output and transverse profiles. In order to measure depth
      doses, a Lucite compensator with an angled surface was fabricated. To test the
      capability of the detector, a proton beam of 10.5 cm range in water was used. The
      distal edge coincided with the overall water equivalent depth upstream of the
      detector on central axis. The measurement was repeated with an additional 1.0 mm
      of solid water placed in front of the detector. The measured profiles from both
      measurements were compared to quantify the IC Profiler response for a small range
      change. RESULTS: The IC Profiler performs within vendor specification for
      measuring machine output and transverse profiles. When measuring depth-doses with
      an angled compensator, the IC profiler measures a change in profile along central
      axis of 17.0% for a 1.0mm range change. Based on overall reproducibility of the
      beam delivery system, the IC profiler is capable of detecting 0.3 mm range shift.
      Therefore, the sensivity of the IC profiler response is suffficient to detect sub
      millimeter changes in delivered range. CONCLUSION: The Sun Nuclear IC Profiler is
      capable of measuring machine output, transverse profiles, and depth-dose profile
      constancy with a high degree of accuracy and precision. Using a single detector
      for all beam measurements increases the overall QA efficiency by reducing
      multiple detector overhead while not sacrificing the accuracy and precision of
      the measurements.

PMID- 28517159
TI  - SU-E-T-138: Quantification of Dwell Position Inaccuracy in Varian GammaMed HDR
      Titanium Ring Applicators.
AB  - PURPOSE: To quantify the dwell position inaccuracy in Titanium ring applicators
      and develop a test to be performed quarterly, after source exchange. METHODS: All
      three rings from our Titanium kit (30, 45, 60 deg.) were used for this study.
      EDR2 film was placed on the Simulator table and a ring was taped to the film,
      with a solid water slab as buildup. A 1-cm spacing dummy wire was inserted into
      the ring. The film was exposed using 135 kV, 80 mA, 400 mAs. An HDR treatment was
      then delivered using the even source dwell positions from 2 to 16, with a 5 mm
      step size, nominal dwell time 0.4 sec/position. The procedure was repeated three
      times for each ring. The films were scanned and analyzed with the RIT software.
      The distance between the center of each source position to the adjacent dummy
      dots was measured for each ring on all three films. An average shift (AS) was
      obtained for each ring.New films were exposed with a treatment offset equal and
      in the opposite direction relative to the AS for the ring used. The films were
      visually inspected to assess if the source positions are centered in between two
      adjacent dummy dots, and also scanned and analyzed with the RIT software. This
      test will be performed quarterly to verify if the shifts remain stable. RESULTS:
      The average shift was 2.5, 2.4, and 2.4 mm distally for the 30, 45, and 60 deg.
      rings, respectively. The offset for the quarterly test was set to 2 mm
      proximally, to take into account the 1 mm tolerance for the source position.
      CONCLUSIONS: The dwell position inaccuracy in Titanium ring applicators was
      quantified and the quarterly test was successfully performed for two quarters.
      Work is started to assess the dosimetric implications of this shift.

PMID- 28517160
TI  - SU-E-T-109: An Evaluation of a Newly Available Portal Dosimetry QA Tool for SRS
      Dynamic Arc and VMAT.
AB  - PURPOSE: In our institute, the MatriXX has been used for IMRT, VMAT and dynamic
      arc QA. However, the small fields (<3cm) shaped by HDMLC for SRS dynamic arc (DA)
      present QA measurement issues when using the MatriXX due to its limited
      resolution (7.6 mm). A recently available portal dosimetry (PD) software tool in
      Eclipse Version 10 is capable of performing QA for arc plans. This study is to
      evaluate this new tool for QA. METHODS: EPID calibration was performed using a
      Varian Novalis TX unit with HDMLCs for a 6X high dose rate SRS beam. The PDIP
      algorithm was configured using measured beam data. Brainlab iPlan was used to
      generate the DA patient treatment plans. The plans were then exported to Aria via
      DICOM RT. A verification plan was created in Eclipse and the predicted portal
      dose calculated. The comparison was done between predicted and measured portal
      dose distributions. RESULTS: Compared with chamber array analysis, the measured
      portal dose shows significant improvement in correlation with predicted dose. To
      eliminate the uncertainty of dose normalization, absolute CU is chosen for
      analysis. Gamma factor was studied. Thecriterion was set at 3%/1mm using a 10%
      dose threshold such that 95% of the pixels had a gamma <1. QA was performed on 9
      plans and the average gamma passing rate is 98.5%, with passing rates ranging
      from 95% to 100%. CONCLUSIONS: With approximately 0.7mm resolution, it is shown
      that the newly available PD tool is capable of overcoming the limitations of
      chamber arrays for small field SRS QA and is also suitable for HDMLC QA to
      provide detailed dose comparison with highly modulated dose profiles within a
      small treatment field. In addition, the time needed to perform the QA procedure
      using the PD tool is significantly shortened compared to the MatriXX.

PMID- 28517161
TI  - SU-E-T-120: Minimum Absorbed Dose Limit for Gafchromic EBT2 Film Response after
      Exposure to Low-Energy Photons.
AB  - PURPOSE: To investigate the accuracy of the absorbed dose measured with
      Gafchromic EBT2 film in low-energy photon radiation fieldsMethods: Six EBT2 film
      (lot # F06110901) pieces (1cm2 ) per dose were exposed to x-rays of 50 kV, 80 kV,
      120 kV and 60Co gamma rays from a Leksell Gamma Knife at dose values from 50 mGy
      to 100 Gy. The x-ray beams were calibrated following the AAPMTG-61 protocol using
      ionization chambers calibrated at NIST or Wisconsin University depending on the
      beam quality, while the 60Co gamma was calibrated in water using MD-V2-55 film.
      Each film piece was scanned once using a HP Scanjet 7650 document flatbed scanner
      in transmission mode, 48-bit color at 300 dpi spatial-resolution. The data
      analysis was made through the ImageJ. The measured light intensity for the red
      channel with its associate standard deviation was used to evaluate the netOD and
      its standard combined uncertainty. The absorbed dose as a function of the netOD
      was fitted using the logistic model and the relative combined uncertainties were
      evaluated for each energy photon beam. RESULTS: EBT2 film response curve depends
      on the low-energy photons and the degree of energy-dependence is a function of
      absorbed dose. The absorbed dose relative combined uncertainty as a function of
      the absorbed dose indicates that the minimum absorbed dose limit is also energy
      dependent. Lower is the energy photon; more accurate is the measurement at low
      dose value. This can be explain by the fact that comparing to high energy
      photons, low energy photons can produce locally enough ionization density to
      create more color centre in the same film area. CONCLUSIONS: Minimum absorbed
      dose limit of Gafchromic EBT2 films were found to be energy dependent. The
      response curve depends on the low-energy photons and the degree of energy
      dependence is a function of absorbed dose This work is partially supported by
      DGAPA-UNAM grant IN102610 and Conacyt Mexico grant 127409.

PMID- 28517162
TI  - SU-E-T-92: on the Use of High-Sensitivity Thermoluminescent Dosimeters (TLDs) for
      Dosimetric Characterization of Low-Energy Brachytherapy Sources.
AB  - PURPOSE: To investigate the utility and accuracy of high-sensitivity TLD for
      dosimetric characterization of low-energy brachytherapy sources. METHODS: One
      hundred high-sensitivity (TLD-100H) and 100 normal-sensitivity (TLD-100) TLDs
      were used in this study. The TLD-100s were annealed at 400 degrees C for one hour
      and then kept at room temperature for 45 minutes followed by 80 degrees C heating
      for 24 hours. To prevent temperature overshot from reducing the sensitivity of
      TLD-100Hs, a novel thermal reservoir was built, tested, and used to anneal TLD
      100H at 240 0C for 15 minutes and then kept at room temperature for 45 minutes
      followed by 100 0C heating for one hour. These TLDs were then irradiated
      uniformly in a large cavity Cs-137 irradiator for biomedical research (Shepherd,
      Mark III) to test their reproducibility and to establish their relative
      sensitivities. The radial dose function of a Model AgX100 125I source was
      measured using both types of TLDs in water-equivalent solid phantoms as a test
      case. The radial dose function measured by the TLD-100H was compared with that
      measured by TLD-100 to determine its utility in brachytherapy dosimetry
      characterization. RESULTS: Consistent and accurate annealing of high-sensitivity
      TLDs was achieved by using a custom-built thermal reservoir system. TLD-100H was
      found to be about 18 times more sensitive than TLD-100. For a 125I source with a
      source-strength of 2.7U, the irradiation time for radial dose function
      characterization up to 7 cm can be cut down from 38 days to 3 days. The radial
      dose function measured by TLD-100H agreed well (within +/-6%) with that measured
      by TLD-100. CONCLUSIONS: A novel thermal reservoir was used for consistent
      annealing of high-sensitivity TLDs. TLD-100H can significantly shorten the
      irradiation time needed for a complete characterization of radial dose function.
      Investigation of TLD-100H for complete brachytherapy source characterization is
      in progress. Supported in part by NIH grant R01-CA134627.

PMID- 28517163
TI  - SU-E-T-131: Influence of Scanning Speed on Measurements of Field Flatness and
      Symmetry of Photon Beams.
AB  - PURPOSE: The purpose of this study was to investigate influence of different
      scanning speeds on measurements of photon beam flatness and symmetry. METHODS:
      Commissioning and quality assurance of linear accelerators require extensive beam
      measurements. To increase efficacy, we evaluated flatness, symmetry and penumbra
      of 6MV photon beam using the Varian-TrueBeamTM system. Scanning speeds were 0.3,
      0.5, 0.75, 1, 1.5, and 2.5cm/s. Measurements were performed in water phantom
      (BluePhantom2 , IBA-Dosimetry) at depths of maximum dose, 5,10, and 20cm, for
      10*10 cm field size. For each scanning speed and depth, measurements were
      repeated five times to give results sufficient statistical significance, in both
      crossline and inline directions. Beam flatness was calculated using variation
      over mean (80%), whereas symmetry was calculated using point difference quotient
      (IEC) algorithm. After filed scanning chamber (Wellhofer) was fully stopped,
      system was paused for stabilization time of 15s to avoid buildup of ripples.
      RESULTS: It was noticed for all measurements that minimum and maximum flatness
      and symmetry were recorded when scanning speeds were 0.3cm and 2.5cm,
      respectively. For depth of maximum dose, maximum flatness and symmetry were 0.82%
      and 100.58% (crossplane), and 0.94% and 100.96% (inplane). The average was 0.76%
      and 100.38% (SD 0.04 and 0.12) for crossplane; 0.89% and 100.87% (SD 0.04 and
      0.06) for inplane measurements. As the scanning depth increased, flatness and
      symmetry increased, but SD for all measurements was within the same range (0.04
      0.07 and 0.04-0.12). The maximum absolute difference for flatness and symmetry
      for maximum and minimum speed were 0.16% and 0.34%.However, for scanning speeds
      from 0.5-1cm/s, results were almost identical with maximum SD 0.03 for both
      flatness and symmetry. Use of different scanning speeds did not influence
      penumbra; SD was 0 for all measurements. CONCLUSIONS: This study reveals small
      influence of scanning speed within predefined range. Consequently, difference in
      measurements does not have clinical significance.

PMID- 28517164
TI  - SU-E-T-122: Dose Response Analysis of Radiochromic Films in Regions of Low Dose
      Using Separation Color Components.
AB  - PURPOSE: To evaluate the dose response of EBT2 films in regions of low dose using
      the decomposition of the image's color channels (RGB, Red, Green and Blue).
      METHODS: Doses ranging from 1 Gy to 60 Gy were used to calibrate the dose
      response of Gafchromic (r) EBT2 films irradiated in 6MV photons beams. Segments
      of film with dimensions of 8.5 cm * 8.5 cm were used. Another segment of film
      with dimensions 8.5 cm * 20.25 cm was also irradiated with a maximum dose of 4Gy
      to determine the percentage depth dose (PDD). The films were digitized by a
      LaserJet M1132 MFP - HP (r) scanner in standard resolution of 150dpi and analyzed
      by a routine created in MatLab to convert the image to gray levels as well as
      assess the desired color components from the image. RESULTS: The green component
      presented the higher sensitivity (17.8 a.u./Gy) when the separated color channels
      and the shades of gray analysis are compared. The red component presented the
      highest signal to noise ratio in the low dose range (63% at 1Gy). The blue
      component presented low sensitivity (0.66 a.u./Gy) in the entire dose range. A
      linear fitting (r=0.998) was used to the green and gray components until a dose
      of 4 Gy. The red component presented a non-linear behavior in the entire dose
      range. The useful dose range found was from 1 Gy to 15 Gy. The maximum
      differences between the reference PDD, measured with ionization chamber in a
      water phantom, and the PDDs determined with film were 6%, 9% and 14% for the
      green, gray and red components, respectively. CONCLUSIONS: This work results show
      that the use of radiochromic films on planning verification procedures in low
      dose ranges can be benefit from the analysis of the image's separated color
      components.

PMID- 28517165
TI  - SU-E-T-94: Multileaf Collimator Performance and Validation of Quality Control
      Tolerances.
AB  - PURPOSE: The automated quality assurance system (AQUA) is a centralized quality
      control (QC) software designed to automate QC tests. Statistical analysis of AQUA
      results was performed to assess the geometric accuracy and long-term
      reproducibility of a commercially available multileaf collimator (MLC) and
      examine the applicability of the American Association of Physicists in Medicine
      (AAPM) tolerances for MLC QC. METHODS: The MLC was first calibrated with AQUA by
      minimizing leaf-positioning errors on megavoltage images for 5 different leaf
      bank positions (-60 to 100 mm from radiation isocenter). Leaf-positioning
      accuracy and reproducibility was assessed by repeating the AQUA test 5
      times/week. The range of leaf-positioning error over leaf-bank positions and time
      was reported. Measured leaf-positioning errors were then separated into
      systematic and random error components. The systematic error corresponds to the
      variation (standard deviation) in mean positioning errors between leaves over
      leaf-bank positions and time. The random error quantifies the leaf position
      variations around its mean and is calculated as the root-mean-square of the
      individual leaf position standard deviations. RESULTS: To date, 2 different MLCs
      have been calibrated using AQUA and 9-18 datasets have been acquired to assess
      performance. For the unit with the longest follow up, the range of leaf
      positioning errors was -0.62 to 0.85 mm and 98% of the measured leaf positions
      (n=7200) were within +/-0.5 mm of the nominal position. The systematic error was
      the main error component (+/-0.15 to +/-0.2 mm) and was attributed to the
      residual errors after calibration. The random error was +/-0.07 mm for both units
      and demonstrated good leaf-positioning reproducibility and limited uncertainty of
      the AQUA measurements. CONCLUSIONS: Preliminary results show that after MLC
      calibration with AQUA, leaf-positioning errors on two different units are well
      within the AAPM-recommended +/-1 mm tolerances. Additional MLC performance
      improvement is possible if residual errors after calibration can be reduced
      further as the MLC demonstrated high reproducibility. Funded in part by Elekta
      Inc.

PMID- 28517166
TI  - SU-E-T-133: Isocenter Measurements with the Winston-Lutz Test: Impact on
      Treatment Planning.
AB  - PURPOSE: To assure high accuracy in radiation delivery during linear accelerator
      based stereotactic radiosurgery procedures, a Winston-Lutz test is typically
      performed to measure the effective isocenter wander over the wide range of gantry
      and couch angles employed. Ideally, this deviation is lower than 1-1.5 mm
      depending on institutional tolerances. Automation of this test with portal
      imaging allows a large amount of data to be taken and processed. This study
      explores the effect of various collimation techniques on beam-center stability,
      and addresses one technique of repositioning in response. METHODS: Winston-Lutz
      shots were obtained using a Trilogy linear accelerator, BrainLab Winston-Lutz
      pointer, and electronic portal imaging from a full range of gantry and couch
      angles. The test was repeated using MLCs, a 10mm stereotactic cone from BrainLab,
      and jaws for beam collimation. All images were processed using an in-house MATLAB
      based program which calculates the distance between the tungsten ball and
      aperture center with accuracy within ~0.1mm. Ideal shifts were calculated by
      minimizing this variation from gantry rotation alone, and performed manually.
      RESULTS: The in-plane gantry sag was found to be on the order of ~0.8mm,
      independent of collimation technique or setup. The MLC carriage had a ~0.3mm
      cross-plane displacement to the inferior from the cone center, negated by a 90
      degree collimator rotation. The total gantry misalignment was greatest near
      gantry 180 (~1.5mm), varying by collimation method. Optimizing to minimize gantry
      error reduced errors to less than 0.7mm but increased the effect of couch
      rotation. CONCLUSIONS: Isocenter evaluation is dependent on collimation method
      used, and should be conducted with the same technique as delivery. It may be
      useful to consider the varying delivery accuracy from different couch/gantry
      angles during treatment planning. Repositioning methods after couch rotation may
      affect ideal laser positions.

PMID- 28517167
TI  - SU-E-T-104: Commissioning and Dosimetric Characteristics of TrueBeam System:
      Composite Data of Three TrueBeam Machines.
AB  - INTRODUCTION: A TrueBeam linear accelerator (TB-LINAC) is designed to deliver
      standard flattened and flattening-filter-free (FFF) beams. In our institute,
      three TB-LINAC units are installed. In this work, composite data of the three
      units and multi-unit comparison are presented. METHODS: Each TB-LINAC can deliver
      photon beams from 4MV to 15MV, electron beams from 6MeV to 22MeV, and 6MV-FFF and
      10MV-FFF. Dosimetric characteristics are systematically measured for
      commissioning including percent depth dose (PDD), beam profile, relative scatter
      factor, dynamic leaf shift, output factor and MLC leakage. Critic considerations
      of Pion of FFF photon beams and dosimetric penumbra are investigated. RESULTS:
      All measured PDDs and profiles of photon and electron matched well across the
      three machines. Beam data were quantitatively compared and combined through
      average to yield composite beam data. The discrepancies among the machines were
      quantified using standard deviation (SD). For example, the mean SD of the PDDs
      among the three units is 0.12%, and the mean SD of the profiles is 0.40% for 10MV
      FFF open fields. The variations of Pion of the chamber CC13 is 1.2+/-0.1% under
      6MV-FFF and 2.0+/-0.5% from dmax to the 18cm-off-axis point at 35cm depth under
      40*40cm2 . The measured relative output factors range from 0.866 to 1.141 with
      the mean discrepancy of 0.06+/-0.04% among the three units. The measured wedge
      factors range from 0.863 to 1.254 with the mean overall discrepancy of 0.04+/
      0.04%. The mean MLC transmission and dynamic leaf shift were measured from 1.0%
      to 1.5% and from 0.77mm to 0.96 mm from 4MV to 15MV. The mean penumbra of various
      photon beams are measured from 5.88+/-0.09mm to 5.99+/-0.13mm from 4MV to 15MV at
      10cm depth of 10*10 cm2 . CONCLUSIONS: Dosimetric data demonstrated that the
      three units could and had been matched well. The systematically measured data
      might be useful for future reference.

PMID- 28517169
TI  - SU-E-T-87: The Effect of Bleaching Wavelengths on the Regeneration of the
      Optically Stimulated Luminescence Signal of NanoDot Dosimeters Pre-Exposed to
      High-Doses.
AB  - PURPOSE: To investigate the effect of bleaching wavelengths on the regeneration
      of optically stimulated luminescence (OSL) signals in Al2 O3 :C nanoDot
      dosimeters pre-exposed to high doses. Regeneration is the increase in the OSL
      signal during storage of a bleached nanoDot that was previously pre-exposed to a
      high dose. This phenomenon affects the accuracy of a calibration protocol
      proposed by Jursinic 2010 (Med. Phys. 37:102) in which pre-exposure of nanoDots
      to a high-dose was used to minimize changes in the sensitivity of the detector as
      a function of accumulated dose. METHODS: Al2 O3 :C OSLDs of the type nanoDot were
      used throughout this study. Readout was performed using the microStar reader.
      Bleaching of the OSLDs was performed with four 26 W fluorescent light bulbs in
      two modes: (i) directly under the lamps; and (ii) with the aid of a long-pass
      optical filter placed over the nanoDots, partially blocking wavelengths below 495
      nm. Eighteen nanoDots were pre-exposed to 1 kGy dose. Then the pre-exposed
      nanoDots were bleached in two sets of 9 to very low residual OSL signals using
      bleaching modes (i) and (ii) for 12 h and 45 h, respectively. The nanoDots were
      then stored in dark and readout after various time intervals to monitor the
      regeneration of the OSL signal. RESULTS: We fitted the regeneration of the OSL
      signal using a saturation function and obtained rise-time values of 563 h and 630
      h, for bleaching modes (i) and (ii), respectively. At the saturation level, the
      equivalent doses were about 1.18 Gy and 0.38 Gy for modes (i) and (ii),
      respectively. CONCLUSIONS: The regeneration rates of nanoDot OSLDs pre-exposed to
      high doses depend on the bleaching light wavelength used to reset the detectors.
      A bleaching source that has a low component of wavelengths below 495 nm can
      minimize the regeneration of the OSL signal. Natural Sciences and Engineering
      Research Council of Canada.

PMID- 28517168
TI  - SU-E-T-115: A Novel Cylindrical 3D Water Scanner for Beam Data Collection: II.
      Dosimetric Characteristics.
AB  - PURPOSE: To study the dosimetric characteristics of a commercial three
      dimensional water scanner (3D SCANNER, Sun Nuclear Corp). The novel cylindrical
      scanner uses a compact electrometer mounted on the side of the tank, eliminating
      the need for chamber extension cables. The electrometer has a wide dynamic range,
      requiring no gain adjustment as scanning conditions change, e.g., field size,
      dose rate, wedge field, etc. METHODS: Measurements from the 3D SCANNER were
      compared against those from another commercial scanner (Blue Phantom, IBA
      Dosimetry). Comparable collection intervals and scanning speeds were used on both
      systems. Profile and depth measurements were performed for open field beams (6
      and 18 MV; 10-cm and 30-cm squared fields; depths of dmax, 10, and 30 cm) and
      wedged fields (6 and 18 MV; 30-cm squared field; depth of 10 cm). Electron beam
      profile and depth measurements were performed for a 20-cm squared applicator (6,
      12, and 20 MeV; depth of dmax). The root mean square (RMS) values were determined
      for each scanner's measurements. RESULTS: The measured field sizes were within
      0.06 cm and 0.05 cm for photon and electron beams, respectively. The photon
      D10/D20 ratios differed by < 0.4% and the electron I50 values were within 0.02
      cm. The RMS of the profiles was approximately 0.1% for both the 3D SCANNER and
      Blue Phantom measurements. Between the two scanners, all measurements agreed
      within RMS, excluding the penumbra region. Two exceptions occurred: a 0.5%
      difference was observed in the shoulder of the 12 MeV profiles, and a 0.8%
      difference was observed in the 6 MeV depth measurements near the surface.
      CONCLUSIONS: The quality of the scanned profile and depth measurements from the
      3D SCANNER is comparable to that of another commercial scanner. Both scanning
      systems have similar levels of scanning noise. This work was partially supported
      by a research grant from Sun Nuclear Corp., Melbourne, FL.

PMID- 28517170
TI  - SU-E-T-126: Non-Reference Condition Correction Factor KNR of Typical Radiation
      Detectors for the Dosimetry of High-Energy Photons.
AB  - PURPOSE: To correct for the deviations of the detector response when typical
      radiation detectors are used under non-reference conditions, factor kNR was
      calculated from the known energy dependence of the detector response at photon
      energies from 10 keV upwards and from clinical photon spectra within a large
      water phantom beneath a Siemens Primus 6/15 MV linac. A Farmer type ion chamber
      (NE2571), two TLD detector types and two diodes were investigated. METHODS:
      Factor kNR was obtained as the ratio of the weighted responses Yt of a given
      detector t under reference conditions xref (axial distance r = 0 cm, depth d = 10
      cm, field size 10 * 10 cm2 and SSD = 100 cm) and that under non-reference
      conditions * (off-axis points and depths for various field sizes); kNR =
      Yt(xref)/Yt(x). For small field (SF) dosimetry, we evaluated correction factor
      kNRSF, which refers to small field reference conditions (4 * 4 cm2 field).
      RESULTS: For all detectors investigated, the deviations of kNR from unity were
      highest outside the field, due to prevailing low-energy scatter contributions.
      For the Farmer chamber and EDP-10 diode, the kNR deviations did not exceed 2%,
      but were up to 60% for the EDD-5 diode, while kNR values for LiF:Mg,Cu,P and
      LiF:Mg,Ti deviated at most 15% and 5% respectively. kNR values appear as unique
      functions of the mean photon energy at the point of interest. CONCLUSIONS: Air
      filled ion chambers show only small kNR variations, while for non-water
      equivalent detectors, kNR variations depend on the detector response at low
      photon energy. kNR can be presented as a unique function of the mean photon
      energy at the point of interest. A 4 * 4 cm2 reference field is recommended for
      small fields, with correction factor kNRSF varying almost negligibly from kNR
      except for unshielded Si diodes.

PMID- 28517171
TI  - SU-E-T-98: Towards Cell Nucleus Microdosimetry: Construction of a Confocal Laser
      Scanning Fluorescence Microscope to Readout Fluorescence Nuclear Track Detectors
      (FNTDs).
AB  - PURPOSE: To construct a custom confocal laser scanning microscope (CLSM) capable
      of resolving individual proton tracks in the volume of an Al2 O3 :C,Mg
      fluorescent nuclear track detector (FNTD). The spatial resolution of the FNTD
      technique is at the sub-micrometer scale. Therefore the FNTD technique has the
      potential to perform radiation measurements at the cell nucleus scale. METHODS:
      The crystal volume of an FNTD contains defects which become fluorescent F2+
      centers after trapping delta electrons from ionizing radiation. These centers
      have an absorption band centered at 620 nm and an emission band in the near
      infrared. Events of energy deposition in the crystal are read-out using a CLSM
      with sub-micrometer spatial resolution. Excitation light from a 635 nm laser is
      focused in the crystal volume by an objective lens. Fluorescence is collected
      back through the same path, filtered through a dichroic mirror, and focused
      through a small pinhole onto an avalanche photodiode. Lateral scanning of the
      focal point is performed with a scanning mirror galvanometer, and axial scanning
      is performed using a stepper-motor stage. Control of electronics and image
      acquisition was performed using a custom built LabVIEW VI and further image
      processing was done using Java. The system was used to scan FNTDs exposed to a 6
      MV x-ray beam and an unexposed FNTD. RESULTS: Fluorescence images above the
      unexposed background were obtained at scan depths ranging from 5 - 10 micrometer
      below the crystal surface using a 100 micrometer pinhole size. CONCLUSIONS:
      Further work needs to be done to increase the resolution and the signal to noise
      ratio of the images so that energy deposition events may be identified more
      easily. Natural Sciences and Engineering Research Council of Canada.

PMID- 28517172
TI  - SU-E-T-137: The Response of TLD-100 in Mixed Fields of Photons and Electrons.
AB  - PURPOSE: Thermoluminescent dosimeters are used routinely for dosimetric
      measurements of photon and electron fields. However, no work has been published
      characterizing TLDs for use in combined photon and electron fields. This work
      investigates the response of TLD-100 (LiF:Mg,Ti) in mixed fields of photon and
      electron beam qualities. METHODS: TLDs were irradiated in a 6 MV photon beam, 6
      MeV electron beam, and a NIST traceable cobalt-60 beam. TLDs were also irradiated
      in a mixed field of the electron and photon beams. All irradiations were
      normalized to absorbed dose to water as defined in the AAPM TG-51 report. The
      average response per dose (nC/Gy) for each linac beam quality was normalized to
      the average response per dose of the TLDs irradiated by the cobalt-60
      standard.Irradiations were performed in a water tank and a Virtual WaterTM
      phantom. Two TLD dose calibration curves for determining absorbed dose to water
      were generated using photon and electron field TLD response data. These
      individual beam quality dose calibration curves were applied to the TLDs
      irradiated in the mixed field. RESULTS: The TLD response in the mixed field was
      less sensitive than the response in the photon field and more sensitive than the
      response in the electron field. TLD determination of dose in the mixed field
      using the dose calibration curve generated by TLDs irradiated by photons resulted
      in an underestimation of the delivered dose, while the use of a dose calibration
      curve generated using electrons resulted in an overestimation of the delivered
      dose. CONCLUSIONS: The relative response of TLD-100 in mixed fields fell
      consistently between the photon nd electron relative responses. When using TLD
      100 in mixed fields, the user must account for this intermediate response to
      avoid an over- or underestimation of the dose due to calibration in a single
      photon or electron field.

PMID- 28517173
TI  - Breast cancer awareness among Indonesian women at moderate-to-high risk.
AB  - In this descriptive cross-sectional study, we examined awareness of breast cancer
      among Indonesian women at moderate-to high-risk of developing breast cancer. Data
      were obtained from 87 eligible participants using the Modified Breast Cancer
      Awareness Measure. The International Breast Cancer Intervention Study model was
      used to identify women at moderate-to-high risk of developing breast cancer. The
      data were analyzed using descriptive statistics. The results showed that none of
      the participants had knowledge of age-related risk (0%). Other domains that
      indicated low awareness were knowledge of lifetime risk (31%), followed by
      knowledge of risk factors, in particular the item regarding menstruation at an
      early age (12.6%). These results indicated that increasing awareness of breast
      cancer risks is highly needed, in particular among women at moderate-to-high risk
      of developing breast cancer in Indonesia.

PMID- 28517174
TI  - High-Pressure NiAs-Type Modification of FeN.
AB  - The combination of laser-heated diamond anvil cells and synchrotron Mossbauer
      source spectroscopy were used to investigate high-temperature high-pressure
      chemical reactions of iron and iron nitride Fe2 N with nitrogen. At pressures
      between 10 and 45 GPa, significant magnetic hyperfine splitting indicated
      compound formation after annealing at 1300 K. Subsequent in situ X-ray
      diffraction reveals a new modification of FeN with NiAs-type crystal structure,
      as also rationalized by first-principles total-energy and chemical-bonding
      studies.

PMID- 28517175
TI  - Comparison of the Human A2A Adenosine Receptor Recognition by Adenosine and
      Inosine: New Insight from Supervised Molecular Dynamics Simulations.
AB  - Adenosine deaminase converts adenosine into inosine. In contrast to adenosine,
      relatively little attention has been paid to the physiological roles of inosine.
      Nevertheless, recent studies have demonstrated that inosine has neuroprotective,
      cardioprotective, immunomodulatory, and antidepressive effects. Inosine was
      recently shown to be a less potent agonist than adenosine at the A2A adenosine
      receptor. To better depict the differences in the mechanisms of receptor
      recognition between adenosine and inosine, we carried out supervised molecular
      dynamics (SuMD) simulations, and the results are analyzed herein.

PMID- 28517176
TI  - SU-E-T-399: Dosimetric and Geometric Evaluation of a Novel Stereotactic
      Radiotherapy Device for Breast Cancer: The GammaPod.
AB  - PURPOSE: A dedicated stereotactic irradiation device, the GammaPodTM, was
      developed to treat early stage breast cancer. This study presents the first
      description of the dosimetric and geometric characteristics from the prototype
      unit. METHODS: The GammaPod stereotactic radiotherapy device is an assembly of a
      hemi-spherical source carrier containing 36 Co-60 sources, a tungsten collimator,
      a dynamically controlled treatment table and a breast immobilization cup embedded
      with a stereotactic coordinate system. The source carrier and the variable-size
      collimator rotate synchronously to form 36 non-coplanar, concentric arcs focused
      at the isocenter. The treatment table enables motion in three dimensions
      facilitating continuous dose painting in comparison to a sphere packing approach.
      Geometric and dosimetric evaluations and a method for absorbed dose calibration
      are provided. Dosimetric verifications of the dynamically delivered plans are
      performed for eight patients in hypothetical pre-op, post-op and dose painting
      treatment scenarios. RESULTS: Loaded with a cumulative activity of 4320 Ci, the
      GammaPod unit delivers 5.31 Gy/min at the isocenter. Due to non-coplanar beam
      arrangement and dynamic dose shaping features, the GammaPod delivers uniform
      doses to the targets with excellent conformity. The spatial accuracy of the
      device is less than 1 mm. Single shot profiles with the 25 mm collimator are
      measured with radiochromic film and found to be in good agreement with respect to
      the MC based calculations (congruence of FWHM less than 1 mm). Dosimetric
      verifications corresponding to all treatment plans corresponding to three target
      scenarios for each of the eight patients demonstrated Gamma index pass rates
      greater than 97%. CONCLUSIONS: The first description of the dosimetric and
      geometric evaluation of the GammaPod was performed. The observed level of
      agreement between the treatment planning system calculations and dosimetric
      measurements has confirmed that the system can deliver highly complex treatment
      plans with remarkable geometric and dosimetric accuracy. C Yu and J Zhang have
      commercial affiliations with Xcision Medical Systems.

PMID- 28517177
TI  - SU-E-T-410: Spine Radiosurgery Imaging Guidance Using ExacTrac and CT on rails.
AB  - PURPOSE: To evaluate the patient setup accuracy and effectiveness using ExacTrac
      and CT_on_rails systems. METHODS: We used Brainlab's Exactrac system and
      Varian/GE's CT_on_rails for spine radiosurgery patient setup. Once the patient
      was setup using the ExacTrac and couch position was recorded, fiducially markers
      were placed on stable surfaces based on the room laser to indicate the linac iso
      for the CT images. CT images were acquired using the on-rail CT with the couch
      rotated 180 degrees. The couch was returned to 0 degree position, and
      verification X-ray images were taken and corrections were made by ExacTrac. The
      treatment CT images were registered with the planning CT using the in-house CAT
      software and it displays the correct couch position based on CT which can be
      compared with ExacTrac setup. The corrected couch positions from CT registration
      are compared to those from ExacTrac. The translational discrepancies needed to be
      within 2 mm for confirmation. If a discrepancy was greater than 2 mm,
      investigation or re-setup was required. The rotation deviations were also
      evaluated by ExacTrac and confirmed by the treatment CT images. We would also re
      setup patient if Exactrac detected more than 3 degree rotation, or treatment CT
      images showed significant target rotation compared to planning CT. The use of the
      CTonrails took little extra time, but make the overall evaluation process easier,
      faster and with more confidence. RESULTS: for 171 treatment sessions using this
      approach, the mean discrepancies between CTonrails and ExacTrac setup is: x=0.0+/
      1.0 mm, y=-0. 1+/-0.9 mm, z=0.2+/-0.9 mm; for rotations, about 3% of the cases
      required re-setup patient due to significant rotation displayed by the treatment
      CT on the CAT system. CONCLUSIONS: The combined use of ExacTrac and CT_on_Rails
      systems can improve the overall setup accuracy and increase the confidence in
      setup for spine radiosurgery treatments.

PMID- 28517179
TI  - SU-E-T-413: Dose Verification for Linac-Based SRS Commissioning and Patient
      Specific QA.
AB  - PURPOSE: Stereotactic Radiosurgery (SRS) program commissioning is currently
      relied on Radiological Physics Center (RPC) Head Neck phantom with Thermo
      Luminescent Dosimeters (TLDs) for dose verification. However, due to the limited
      accessibility of RPC Head Neck phantom, ongoing QA or patient specific dose
      verification is not performed in most clinics. In this study, we proposed an SRS
      dose verification approach for both SRS commissioning and patient specific dose
      verification with widely available clinical instruments. METHODS: SRS treatment
      plans were imposed onto a 14cm thick conventional solid water phantom (30cm *
      30cm), with a PTW micro-chamber in the middle. Treatment couch angles were
      renormalized to 90 or 270 degrees for two reasons: 1) micro-chamber's axis was
      parallel to gantry rotation axis during all the arc beam delivery, which
      minimizes the angle dependence effect (axis tilt) of micro-chamber. 2) Any
      collision between the cone and conventional solid water phantom would be avoided
      and there would be minimum attenuation effect from the couch. The arc
      verification plan was then recalculated and compared to the measured absolute
      dose by PTW micro-chamber. An End-to-End test with a CyberKnife Head Neck phantom
      and GAFChromic EBT2 film was utilized as secondary dose delivery verification.
      RESULTS: Cones with all twelve different sizes in SRS commissioning were tested.
      For the cone size from 10mm to 30mm, the micro-chamber measurements agreed with
      the computer calculations within 3%. However, when the cone size was reduced to
      5mm, micro-chamber measurement was 10% lower than planned dose, indicating
      underdose effect for small cone size. Additional measurements with Cyberknife
      head phantom confirmed the dose delivery accuracy was within 5%. CONCLUSIONS: A
      simple SRS dose verification method which only requires micro-chamber and
      conventional solid water phantom has been presented and verified. This approach
      will be valuable for SRS commissioning and ongoing SRS QA.

PMID- 28517178
TI  - SU-E-T-431: Investigation of BrachyVisionTM AcurosTM Using Varian Surface
      Applicators.
AB  - PURPOSE: Conical brachytherapy surface applicators with diameters ranging from 10
      mm to 45 mm have been developed by Varian Medical Systems, Inc. These applicators
      are designed to be used with the GammaMedplus iX and VariSource iX high-dose rate
      Ir-192 afterloaders, allowing for conformal dose delivery for the treatment of
      surface lesions. Treatment plans for these applicators are created in
      BrachyVision Acuros. Few studies have been completed with Acuros in clinical
      situations. The purpose of this work is to perform a comparison of the Acuros
      calculated dose distributions with those calculated using Monte Carlo and
      measured with various detectors. METHODS: Surface applicator treatment plans for
      each source/applicator combination were created using Acuros and a virtual water
      phantom. Simulations to characterize the dose distributions were completed using
      MCNP5 based on specifications provided by the manufacturer. A collision kerma
      tally was used to determine the dose distributions at the surface and at depth in
      water. Experimental verification of the depth-dose and surface dose distributions
      was completed using an ionization chamber, and TLDs and film, respectively.
      Acuros-calculated depth-dose and isodose values were compared to the Monte Carlo
      and experimental values. RESULTS: Assessment of the surface dose distributions
      shows a peak at the center of the applicator with rapid fall off to the edges.
      The TPS-calculatedpercentage depth-dose curves were within 3.7% of the MC and
      5.8% of the measured for the 30 mm applicator and were within 4.4% of the MC and
      measured for the 35 mm applicator. CONCLUSIONS: BrachyVision Acuros is capable of
      calculating the depth-dose and surface dose distributions for the simple water
      phantom case with surface applicators. Investigation of additional treatment
      geometries and applicators is ongoing. Conflict ofInterest: Varian Medical
      Systems, Inc. provided financial support, software, sources, and applicators.
      Varian Medical Systems, Inc. provided financial support, software, sources, and
      applicators.

PMID- 28517180
TI  - SU-E-T-424: Inter-Fraction Variation of High Dose Regions of OARS in MR Image
      Based Cervix Brachytherapy Using Rigid Registration.
AB  - PURPOSE: To quantify the inter fraction variation of spatial location of high
      dose regions of OARs in MR-image based cervix brachytherapy using rigid
      registration algorithm. METHODS: Retrospective analysis of 27 previously treated
      patients under EMBRACE multi-centric trial was evaluated. Each patient had two
      applications, API and AP2 with Vienna applicator. As part of the protocol, all
      patients underwent MR imaging for each application, followed by volume
      delineation (Oncentra v3.3) treatment planning & optimization (Plato sunrise,
      Nucletron), documentation of DVH parameters based on GEC-ESTRO recommendations.
      The volume receiving the dose D2cc from the plan with which the patient was
      treated was contoured in each of the image series for OARs rectum, bladder,
      sigmoid and small bowel region. Both the image series were exported to Eclipse
      planning system (v8.6.14, VMS) and were co-registered with applicator as the
      reference using rigid registration Results: Out of 27 patients, the overlapping
      D2cc volumes were found in 21, 20, 10 and 4 patients for rectum, bladder, sigmoid
      and small bowel respectively between AP1 and AP2. The mean(SD) volume of overlap
      of D2cc was 0.20(0.23), 0.17(0.20), 0.07(0.14), and 0.09(0.11) for rectum,
      bladder, sigmoid and small bowel respectively. The overlap volume had a wide
      range which is evident from its standard deviation. The mean(SD) difference of
      the absolute volumes between AP1 and AP2 was 22(20), 5(6), and 11(11) for
      bladder, rectum and sigmoid respectively. The uncertainties include the
      calculation of small overlapping volumes of D2cc, co-registration and variation
      between applications. CONCLUSIONS: The inter-fraction variation of spatial
      location of high dose regions were more consistent in rectum and bladder and less
      in sigmoid and much lesser in small bowel region.

PMID- 28517181
TI  - SU-E-T-435: Automatic Monte Carlo Dose Calculations of Proton Treatment Plans.
AB  - PURPOSE: Providing a user friendly automated Monte Carlo dose computation system
      for proton treatments using passively scattered and intensity modulated proton
      therapy plans, developed at the proton therapy facility of the M.D. Anderson
      Cancer Center. METHODS: In house software was developed to automatically extract
      patient CT images, as well as the setup geometry and proton beam parameters from
      DICOM files, to create a Monte Carlo (MCNPX) model simulating the beam line
      arrangements of the various beams used in any given proton treatment plan. A
      graphical user interface provides an easy and intuitive workspace. A library of
      phase space files provides source proton beams with the desired modulation width
      and range in water. Energy deposition is scored in the voxelized CT volume,
      converted to dose and compared to results of analytical dose computations.
      RESULTS: Monte Carlo models of patient specific beam line equipment, such as the
      brass collimator and the range compensator, as well as avoxelized model of the
      patient, are automatically created and implemented into the model of the
      simulated beam. Simulation of proton beams result in energy deposition
      distributions in a volume of interest defined by the user during program start.
      CONCLUSIONS: Current efforts focus on production ofthe phase space library and
      final debugging of the program flow. It is expected that a prototype version of
      the system will be functional in summer 2012.

PMID- 28517182
TI  - SU-E-T-401: Evaluation of Initial Setup Accuracy and Intra-Fraction Motion for
      Spine SBRT Using Stereotactic Body Frames.
AB  - PURPOSE: Quantify initial setup accuracy and intra-fraction motion using
      stereotactic body frames (SBF) for spine SBRT. METHODS: 10 patients (11 sites, 31
      fractions) treated with spine SBRT using SBF immobilization were evaluated for
      initial setup accuracy and intra-fraction motion. Either the commercial Elekta
      SBF or an in-house developed SBF (BHS-SBF) were used. The BHS-SBF uses the same
      setup/immobilization principle as the Elekta but with increased interior space
      and couch indexing. Both frames include sidewalls to conform the vac-loc rigidly
      to the patient's sides. All patients were setup using the Brainlab ExacTrac
      system which includes IR and stereoscopic kV x-ray based positioning. Patients
      were initially positioned in the frame using skin tattoos then shifted to
      treatment isocenter based on IR markers affixed to the frame with known geometry
      relative to isocenter. kV imaging was acquired and automatic 6-D bony fusion
      performed. Resulting translations and rotations give the initial setup accuracy.
      Calculated shifts and rotations were performed using a robotic couch and
      verification imaging acquired. The imaging/fusion process was repeated multiple
      times during treatment providing intra-fraction motion data. RESULTS: Mean
      initial setup error in the VRT, LNG and LAT directions was 0.1+/-3.0 mm (0.1+/
      0.6 deg), 0.5+/-5.2 mm (0.1+/-1.1 deg) and -0.3+/- 3.7 mm (0.4+/-0.8 deg)
      respectively. Mean 3-D error magnitude was 6.6 mm with a 95% certainty of 11.2
      mm. Mean intra-fraction shifts observed in the VRT, LNG and LAT directions were 
      0.1+/-0.4 mm, -0.1+/-0.4 mm and 0.1+/-0.3 mm respectively. Mean 3-D intra
      fraction shift magnitude was 0.6 mm with a 95% certainty of 1.4 mm. No
      significant difference was observed between the SBFs. CONCLUSIONS: Patient
      positioning is not sufficiently reproducible with the evaluated SBF to allow non
      image guided treatment. However, provided image guidance is used for patient
      positioning, these frames provide excellent immobilization which is on par with
      mask based cranial radiosurgery.

PMID- 28517183
TI  - SU-E-T-417: Tomotherapy Isocentricity: Is it Good Enough for Stereotactic
      Radiosurgery?
AB  - PURPOSE: To evaluate the isocenter accuracy of radiation beam relative to the
      Tomotherapy linear accelerator's mechanical axis using a simplified Winston Lutz
      test, and to determine if Tomotherapy system is accurate for SRS applications.
      METHODS: BrainLab Winston Lutz pointer was setup on the Tomotherapy couch to the
      isocenter according to the green lasers. Four static plans were created to
      deliver radiation with 1cm jaw opening, all MLC closed except the central two
      leaves, and gantry at 0, 90, 180 and 270 degree, respectively. Gafchromic EBT
      films were taped on a solid water slab and placed on opposite side of gantry at a
      fixed distance for each plan. After the exposure, the films were scanned using
      Vidar scanner along with a 1 cm scale drawn (Figure 1-A, 2-A). The images were
      first processed by ImageJ, using Find Edges function to enhance the visibility of
      the boundaries of the circles, from a metal ball in the pointer, and the
      rectangles defined by two central leaves and the jaws (Figure 1-B, 2-B). Then two
      diagonal lines were drawn on each rectangle, and a cross on each circle, with the
      cross sections representing the centers of the rectangles and circles,
      respectively (Figure 1-C, 2-C). RESULTS: The displacements of the centers of the
      circles from the centers of the rectangles for the first setup (films were 11cm
      from the isocenter) were 0.50, 0.707, 1.0 and 0.707 millimeters for each gantry
      angle, respectively, with an average of 0.73mm. The displacements of second setup
      (films were 25cm from the isocenter) were 0.54, 1.07, 0.87 and 0.54 millimeters,
      with an average of 0.75mm. CONCLUSIONS: The preliminary data show that the
      radiation isocenter agrees with mechanical isocenter well within one millimeter
      tolerance required for SRS treatments, which indicated Tomotherapy system is
      suitable for such applications.

PMID- 28517184
TI  - SU-E-T-384: An Easy Use Anthropomorphic Phantom for Lung IMRT QA.
AB  - PURPOSE: Even though lung IMRT plans are calculated based on patient CT with
      heterogeneity correction, patient-specific validations are often performed by
      using measurements in homogeneous solid media. In this study we developed
      heterogeneous phantoms for measurement-based validation of lung IMRT. METHODS:
      Three slabs from thorax region of anthropomorphic RANDO phantom and virtual water
      (VW) slabs were used to construct two versions of heterogeneous phantom, "Hetero
      1" and "Hetero-2". The RANDO slabs are 2.5 cm thick. A two-dimensional diode
      array detector, MapCHECK and an ion chamber were used for measurements. "Hetero
      1" consisted of three RANDO slabs placed horizontally on the MapCHECK plus a 3cm
      VW on the top. Hetero-2 was constructed by inserting a 2 cm VW with a chamber
      cavity on top of the first RANDO slab above the MapCHECK. Two lung-IMRT plans
      were generated using Pinnacle TPS, including a plan for the RPC Lung-Phantom. The
      point doses were compared with ion chamber measurements and planar dose were
      compared with MapCHECK measurements. RESULTS: The MapCHECK measurements were
      performed using "Hetero-1" on a beam-by-beam basis for the two IMRT plans.
      Passing rates under 3%/3mm Gamma criteria of were from 93.5% to 98.5% for all
      beams. Accumulative measurements were performed using "Hetero-2" and the passing
      rates under same criteria for two IMRT plans were 96.9% and 96.3% respectively,
      and 95.2% and 98.5% for measurements with 5cm lateral-IsoCenter-shift including
      more lung material. The differences between Ion-chamber- measurements and TPS
      calculations were 1.2% and 1.71% for two IMRT plans. In vivo results obtained
      from RPC-report for two TLDs inside the PTV were 98% and 99% between measurements
      and calculations. CONCLUSIONS: An easy-to-setup heterogonous phantom for Lung
      IMRT QA can be constructed by adopting thorax region slabs of anthropomorphic
      type phantoms. It can be implemented as a convenient and efficient tool for lung
      IMRT QA in a routine clinic.

PMID- 28517185
TI  - SU-E-T-428: Class Solution for Prostate High Dose Rate Brachytherapy with Inverse
      Planning Simulated Annealing.
AB  - PURPOSE: To develop and validate a class solution for inverse planning simulated
      annealing (IPSA) with CT based prostate high dose rate brachytherapy (HDR).
      METHODS: Between November 2008 and November 2011, our institution treated 40
      prostate cancer patients with HDR in 7 Gy fractions followed by external beam
      radiotherapy. The HDR treatments were planned with Nucletron Oncentra using
      manual graphical optimization (GO). Plans were optimized to the following
      clinical goals: = 95% of prostate volume received 7 Gy, < 1 cc of rectum received
      5.6 Gy, < 0.1 cc of rectum received 6.3 Gy, and < 0.01 cc of urethra received
      8.75 Gy. New plans were manually customized using IPSA (MC-IPSA) for each patient
      to match prostate coverage by the prescription dose to within +/- 1% of the GO
      plans while meeting the rectal and urethral dose constraints. An IPSA class
      solution (CS-IPSA) was created from the mean MC-IPSA parameters. New plans were
      developed for each of these 40 patients using only CS-IPSA with no further
      optimization. Additionally, plans were created on an independent dataset of 30
      different patients using only CS-IPSA with no further optimization. RESULTS:
      Plans were optimized in about 30 minutes using GO, MC-IPSA took an average of
      14.1 +/- 6.5 minutes, and CS-IPSA optimizationwas < 1 minute. There was no
      significant difference (p > 0.05) among the optimization methods for all clinical
      goals over the 40 CS-IPSA source patients. There was no significant difference (p
      > 0.05) between the source and the independent datasets for all clinical goals
      when using CS-IPSA with no further optimization. CONCLUSION: A prostate HDR IPSA
      class solution was developed and validated on a source and an independent
      dataset. The IPSA class solution yields plans comparable to custom manual IPSA
      and graphical optimization while saving considerable time.

PMID- 28517186
TI  - SU-E-T-394: Comparison of Planned Dose Distribution Vs. Delivered Dose
      Distribution for Both IMRT and Proton Therapy Using Weekly Repeat 4DCT Data Sets.
AB  - PURPOSE: To evaluate treatment deviations and the impact of treatment modality in
      the presence of breathing motion and anatomical changes during the course of lung
      cancer radiotherapy. METHODS: Two non-small cell lung cancer patients were
      enrolled in a randomized clinical trial to compare IMRT and proton therapy. To
      rigorously evaluate the impact of motion and anatomical changes, we used a '5D'
      dose accumulation approach to sum dose distributions from phase-to-phase and week
      to-week to the reference (end-expiration) phase of the original planning 4DCT
      data set. Six to eight weekly 4DCT data sets that consisted of 10 breathing
      phases were acquired during the treatment course. The original plan was re
      calculated for each phase and deformably mapped to the reference phase to compare
      the 'delivered' dose distribution with the planned dose distribution of both the
      IMRT plan and the proton plan for each patient. DVHs derived from delivered dose
      distribution were compared to that from the planned dose distribution. RESULTS:
      The delivered dose showed 3% and 2% increase in the dose to the CTV for IMRT and
      proton plan respectively. Target coverage remained acceptable despite tumor
      shrinkage from 29% to 49%. The doses to normal structures, such as lung and
      heart, increased more in the proton plan than in the IMRT plan. The V20 of the
      total lung volume increased by 4% and 6% from the delivered dose compared to the
      planned dose for IMRT and proton plan, respectively. CONCLUSIONS: The results
      showed sufficient target coverage was maintained for both modalities. Increases
      in lung dose were observed in both modalities, but more in the proton arm,
      perhaps due to weight loss and tumor shrinkage. Adaptive proton therapy strategy
      is recommended to minimize normal tissue doses. Supported in part by NCI P01
      CA021239-29A1.

PMID- 28517187
TI  - SU-E-T-439: First Experience of Three Dimensional Conformai Radiotherapy (3DCRT)
      Planning with Helical Tomotherapy.
AB  - PURPOSE: A three-dimensional conformal radiotherapy (3DCRT) has been recently
      introduced to helical tomotherapy, allowing the user to plan and treat patients
      that do not require sophisticated IMRT planning and delivery. This study aims to
      test treatment planning on this modality and evaluate its performance by
      comparing to conventional LINAC-based 3DCRT planning. METHODS: Four clinical
      cases (whole brain, extremity, lung, and partial breast irradiation) were
      retrospectively selected from a Pinnacle planning system (Philips Medical System,
      Fitchburg, WI) and planned on Tomotherapy (Accuray Inc., Sunnyvale, CA). Computed
      tomography (CT) images together with contours of target and critical structures
      were exported from Pinnacle to the Tomotherapy planning station. The same
      prescription and fractionation scheme was adopted. The pitch factor for all
      clinical cases was set to 0.287. A 2.5 cm jaw was employed except in the lung
      case the field size was set to 1.0 cm for better dose conformity. The dose grid
      size was chosen to be half of that of the planning CT images. On Pinnacle 100%
      prescription dose was delivered to the treatment isocenter while onTomotherapy it
      was stipulated that at least 95% of the target volume received the prescribed
      dose. Comparison between two planning strategies was performed, in terms of dose
      volume histograms (DVH), dosimetric and radiobiological parameters, for plan
      quality assessment. RESULTS: Comparison of DVHs reveals that up to 25% healthy
      tissue sparing in volume can be accomplished with Tomotherapy 3DCRT while the
      same target coverage is ensured. Dosimetric and radiobiological indices between
      Tomotherapy and Pinnacle planning agree to within 3.0%. Additional beam modifiers
      and non-coplanar beams associated with LINAC-based 3DCRT are not needed on
      Tomotherapy, making it more favorable. CONCLUSIONS: Tomotherapy 3DCRT has similar
      dosimetric performance when compared to conventional LINAC-based 3DCRT while it
      is substantially easier to use.

PMID- 28517188
TI  - SU-E-T-405: A Whole-Procedure Winston-Lutz Test for Quality Assurance of a Bite-
      Block Based Extend Frame System for Delivering Multi-Session Stereotactic
      Radiosurgery.
AB  - PURPOSE: To develop a whole-procedure Winston-Lutz (WL) test method to determine
      the full system accuracy of a vacuum-assisted bite-block based frame system for
      multi-fraction Gamma Knife radiosurgery in reference to standard metal frame
      based single fraction delivery. METHODS: A patient- specific bite-block frame was
      first modified to incorporate a pin mark and a slanted film holder. Using actual
      treatment protocol, a frame-indexed CT study was obtained and a treatment plan
      was developed accordingly. Then a film was placed and exposed to the pin-point
      position as identified per plan. To minimize signal noise for the exposed film
      where isodose distributions were mostly non-spherical, a band of peripheral dose
      distribution in the range of 40%-60% of central dose was extracted and then the
      average center-of-mass position from the dose band was measured and compared
      against the pin-point position. The test was carried out for initial system
      commissioning as well as patient-specific quality assurance measurements.
      RESULTS: Unlike traditional WL test where the border of an exposed field must be
      precisely demarcated, our current procedure eliminates such requirement via
      averaging a peripheral band of measured point cloud. The final result was more
      robust against random noises and artifacts associated with scatter radiation and
      signal processing. The mean variation against varying bandwidth and repeated film
      exposures was found to be within 0.05+/-0.11 mm. For the initial 21 independent
      treatment deliveries as tested at our institution, the overall system accuracy
      was 0.36+/-0.11 mm, which matched excellently with 0.29+/-0.19 mm as measured for
      a rigid metal frame. CONCLUSIONS: A robust CT-based Winston-Lutz test procedure
      was developed for a multi-session bite-block based stereotactic frame system.
      Submillimeter physical accuracy was established for such a system in a clinical
      setting.

PMID- 28517189
TI  - SU-E-T-387: Validation of a New System for Patient Specific IMRT QA and
      Comparison with Other Commerical Systems.
AB  - PURPOSE: The focus of this project is to compare the Octavius 4D with current
      commercial available dose validation systems: MatriXX MultiCube and Delta4.
      METHODS AND MATERIALS: Many challenges are faced with properly measuring
      Intensity Modulated Radiotherapy (IMRT). It has become common practice for
      clinics to use film, arrays, or multiple detectors to validate dose measurements
      pretreatment for static and dynamic treatments. IMRT QAs for various treatment
      sites were measured for patients using three different dose validation systems.
      All measurements were taken on a Varian CLinac 2100 C/D, SN-757, 80 MLC with 6MV.
      The treatment plans evaluated were Step-N-Shoot. Data analysis was performed
      using the software provided with each dose validation system. Detailed
      information was gathered from each system with their perspective advantages. The
      latest system, Octavius 4D, allows one to calculate the Gamma Index for Coronal,
      Sagittal, and Transversal views for every slice included in the measurement along
      with the traditional data analysis provided; histograms, horizontal and vertical
      profiles, DTA. RESULTS AND DISCUSSION: The Gamma Index values were observed using
      the MatriXX Multicube, Delta4, and Octavius 4D. The treatment plan included five
      fields at various gantry angles. Also the gamma index and profiles were
      calculated for various treatment sites. Delta 4 and the Octavius 4D appears to be
      quite comparable. Each device has the ability to allow one to verify segmented
      and composite fields, measure dose profiles and analysis using the Gamma Method.
      ConclusionsSimilar IMRT QA measurements will be made for more Step-N-Shoot cases
      with the addition of SmartArcs. The limitations of each system will be determined
      for each system using the Gamma Index as a reference while varying the Region of
      Interest, Threshold, and Gamma Method (local, normalization, and maximum dose),
      as well as the 2D- profiles for these cases.

PMID- 28517190
TI  - SU-E-T-398: Verification of Gamma Knife EXtend System Based Fractionated
      Treatment Planning Using EBT2 Film.
AB  - PURPOSE: To present EBT2 film verification of treatment planning with the eXtend
      System, a relocatable frame system for multiple-fraction or serial multiple
      session radiosurgery. METHODS: A human head shaped phantom simulated the
      verification process for fractionated Gamma Knife (GK) treatment. Phantom
      preparation for eXtend Frame based treatment planning involved creating a dental
      impression, fitting the phantom to the frame system, acquiring a stereotactic
      computed tomography (CT) scan. A CT scan (Siemens, Emotion6) of the phantom was
      obtained with following parameters: Tube Voltage - 110 kV, Tube Current - 280 mA,
      pixel size - 0.5 mm * 0.5 mm and 1 mm slice thickness. A treatment plan with two
      8 mm collimator shots and three sector blocking in each shot was made. Dose
      prescription of 4.0 Gy at 100% was delivered for the first fraction out of the
      two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ) was used as 2D
      verification dosimeter in this process. Films were cut and placed inside the film
      insert of the phantom for treatment dose delivery. Meanwhile a set of films from
      the same batch were exposed from 0 Gy to 12 Gy doses for calibration purpose.
      EPSON (Expression 10000XL) scanner was used for scanning the exposed films in
      transparency mode. Scanned films were analyzed with in-house made Matlab codes.
      RESULTS: Gamma index analysis of film measurement in comparison with TPS
      calculated dose resulted in high pass rates >90% for different tolerance criteria
      of 2%/2mm, 1%/1mm, and 0.5%/0.5mm. The isodose overlay and linear dose profiles
      of film measured and computed dose distribution on sagittal and coronal plane was
      in close agreement. CONCLUSIONS: Through this study we propose a treatment
      verification QA method for eXtend frame based fractionated Gamma Knife
      radiosurgery using EBT2 film. Acknowledgement: Authors acknowledge the help of
      Andre Micke, ISP for sharing his expertise on EBT2 film.

PMID- 28517191
TI  - SU-E-T-409: A Comparison of 3D Optical Surface and IR Marker Tracking for Head
      Motion Compensated Frameless SRS.
AB  - PURPOSE: Both infrared marker and 3D facial surface tracking were performed
      simultaneously on both a head phantom and healthy volunteers. Accuracies of the
      two 6D real-time tracking systems were quantitatively assessed both spatially and
      temporally. The suitability of 3D facial surface tracking for providing real-time
      head positioning to guide a robotic head motion compensation stage was
      investigated. METHODS: A xyz stage was programmed to move a head phantom to
      approximately 200 points in 10*10*10 mm3 and 100*100*100 mm3 cubic volumes,
      respectively. Both 3D surface and IR marker tracking were performed
      simultaneously on the head phantom to allow direct comparison of spatial
      accuracy. Sinusoidal motion was performed along all three axis directions and
      recorded under the same clock cycle. Spatial and temporal accuracies on actual
      deformable facial surfaces were assessed by simultaneous 3D surface and IR marker
      tracking on human volunteers. 3D surface tracking both with and without the use
      of robotic head motion compensation was evaluated. RESULTS: For 10 samples at
      each position, the 10 mm cube had RMSE of 0.30 mm and 0.08 mm for the AlignRT and
      Polaris, respectively. Temporal lag of the AlignRT system was found to be
      approximately twice the fps time (t_{lag} ~ 2/fps). The fps value was found to be
      strongly correlated with region-of-interest (ROI) surface size and could vary
      from 0.5 - 1.6 fps, leading to a lag time of 1 - 4 s. The Polaris output lagged
      behind the reference by 0.06 s in all cases. CONCLUSIONS: Both 3D surface and IR
      marker devices demonstrate high spatial accuracy for phantom based studies,
      however, a slight dimensional warping along the SI direction was observed to
      occur with the AlignRT. The current ROI dependent lag time of the AlignRT could
      also pose an issue for image guidance techniques requiring quick response times.

PMID- 28517192
TI  - SU-E-T-412: Can Cyberknife SBRT Be an Alternative to Brachytherapy for Cervical
      Cancer Treatment?
AB  - PURPOSE: To investigate the effectiveness of stereotactic body radiation therapy
      (SBRT) with Cyberknife for treatment of squamous cell carcinoma (SCCa) of cervix
      that are commonly treated with brachytherapy. METHODS: SCCa of cervix is
      routinely treated with external beam radiation therapy (EBRT) followed by
      brachytherapy. Common practice is to use high-dose- rate (HDR) brachytherapy,
      mainly with Ir-192; however, low-dose-rate (LDR) brachytherapy with Cs-137 is
      also used. Three of our patients with cervical SCCa who were chosen to have LDR
      brachytherapy (Cs-137 with tandem and ovoids) could not tolerate the prolonged
      treatment or applicator placement. All these patients previously received 45Gy
      (1.8Gy/fratction) from EBRT and well tolerated. Planned LDR treatment dose and
      time were for patient-1: 42.63Gy in 73.5hr, patient-2: 42.34Gy in 73hr, patient
      3: 41.76Gy in 72hr. Delivered LDR dose and time were: 3.75Gy in 6.5hr, OGy in
      Ohr, and 17.3Gy in 19.8hr, for patient-1, -2 and -3, respectively. Two of the
      three patients tolerated LDR treatment partially; the second patient could not
      tolerate the applicator, which required immediate removal after placement.
      Treatments were completed with Cyberknife SBRT (CK-SBRT)doses of 25Gy, 15Gy and
      25Gy for patient-1, -2 and -3, respectively; all had 5Gy/fraction and
      3fractions/week. Prescriptions were at 80% isododelines; CTV coverages were
      96.6%, 99.9% and 100% for patient-1, -2 and -3, respectively. RESULTS: Till their
      last follow-up in February 2012, all three patients were doing fine clinically
      without any evidence of disease; none of these patients had any complications
      that could be related to CK-SBRT. CONCLUSIONS: Appears that CK-SBRT can be a
      viable treatment alternative to brachytherapy. CK-SBRT may also be more appealing
      to patients and physicians for a variety of reasons such as out-patient
      procedure, shorter treatment time, no need for operating room, and no need for
      applicator insertion and tolerance. However, extensive clinical study is
      warranted in this regard.

PMID- 28517193
TI  - SU-E-T-423: Dosimetric Effect of Rotation on Stereotactic Body Radiotherapy
      (SBRT) of the Spine.
AB  - PURPOSE: To study the dosimetric effects of the residual setup rotation errors in
      spine SBRT. METHODS: We selected 25 patients with 26 lesions from an IRB approved
      registry. All patients were setup with Exactrac IGRT and treated with Novalis.
      Excatrac provided 6D shifts (3 translational, 3 rotational). The translational
      shifts were corrected by moving the couch. The rotational shifts >2 degrees were
      corrected by repositioning the patient, while smaller shifts were ignored. For
      each patient, we rotated the simulation CT rigidly around the CTV center by the
      recorded residual angles, using the MIM 4.22 software. The resulting rotated CT
      with all contours were imported into the TPS. The clinical plans used for
      treatment were mapped onto the rotated CT. Dosimetric endpoints were extracted
      for the rotated CTV (mean, max, D90) and the rotated cord (D0.1cc, D1cc, V10,
      max). These endpoints were compared to those from the clinical plan. RESULTS: For
      the CTV, the average ratio of the mean doses was 1.001 (0.996-1.004), the average
      ratio of D90 was 1.003 (0.998-1.011), and the average ratio of the maximum doses
      was 1.005 (0.995-1.029). For the cord, the average ratio of DO.lcc was 1.01 (0.94
      1.06), the average ratio of D1cc was 1.036 (0.92-1.23), the average max doses
      ratio was 1.03 (0.95-1.11), and the average V10 ratio was 1.43 (0.56-2.78).
      CONCLUSIONS: Rotational errors in patient setup as small as 2 degrees do have
      dosimetric effects in spine SBRT treatments. The use of a robotic table to
      eliminate translational and rotational shifts is strongly recommended. It is
      important to note that, eventhough, the residual rotations resulted in up to 11%
      variation (cord max dose) from the planned doses, none of these cases violated
      our clinical treatment plan acceptance criteria (tolerance of the critical
      organs).

PMID- 28517194
TI  - SU-E-T-434: Use of Deformable Registration for Cumulated Dose Calculation in
      Image-Guided Intracavitary Bracytherapy for Cervical Cancer.
AB  - PURPOSE: The minimum dose to 2 cc of tissue receiving the highest dose (D2cc) has
      been suggested as a surrogate measurement for risk of developing toxicity in
      organs at risk (OARs) in patients receiving image-guided cervical intracavitary
      brachytherapy. Conventional D2cc is typically calculated by simple summation,
      assuming the locations of the hot spots do not vary substantially. This study
      explores the effect of deformable image registration in determining a more
      accurate D2cc of rectum, sigmoid colon, bladder and small bowel. METHODS: Five
      patients, with 2 pelvic CT scans each performed at the time of brachytherapy
      planning, were evaluated. The first scan was performed with an empty bladder (an
      indwelling catheter was in place) and the second with a full bladder (with 180-cc
      sterile water). OARs were contoured on each scan. A symmetric demons algorithm
      with weighted sub-area approach was used to register images from different
      fractions. A pelvic prostate phantom was used to verify the method. After
      registration, the cumulated D2cc (ND2cc) was compared to the conventional D2cc
      (OD2cc) without deformable registration. RESULTS: In all cases, the ND2cc was
      lower than the OD2cc. For full bladder scans, the average difference (range) for
      rectum, sigmoid colon, bladder and small bowel between ND2cc and OD2cc were 28.9
      (1.6 - 56.6)%, 34.7 (5.7 -68.4)%, 12.1 (0.0 -27.7)%, 7.2 (1.1 -22)% respectively.
      For empty bladder scans, the average differences (range) for the above organs
      between the ND2cc and the OD2cc were 30.7 (0.75-56.3%, 20.6 (6.3-39.6)%, 7.5
      (0.88-13.1)%, 12.2(0.0-22.2)% respectively. CONCLUSIONS: A significant difference
      was observed between the ND2cc and the OD2cc with rectum and sigmoid being the
      most variable and bladder the least variable. While further studies are needed to
      evaluate which D2cc method is more useful in predicting late toxicity, we found
      the conventional method often overestimates dose to OARs.

PMID- 28517195
TI  - SU-E-T-416: Performance Test Comparing Three Pre-Treatment Isocenter Localization
      Techniques for Single Fraction Cranial Stereotactic Radiosurgery.
AB  - PURPOSE: To develop a performance test comparing three pre-treatment isocenter
      localization techniques when using head-frame vs. immobilization mask for cranial
      Stereotactic Radiosurgery (SRS). This study will compare pre-treatment
      positioning techniques using laser alignment vs x-ray verification using ExacTrac
      or On Board Imaging. METHODS: A RANDO anthropomorphic head phantom was fitted
      with an in-house polystyrene insert to allow EDR2 film measurements in two
      orthogonal planes. A pin hole was pricked on each film to serve as a target
      during treatment planning. for each trial (three total), a CT scan was acquired
      of the phantom equipped with either an immobilization mask or invasive head
      frame. Treatment planning employed iPlan Image v4.1 and iPlan Dose v4.1.1.
      Positioning of the phantom equipped with the head-frame was performed by aligning
      vault lasers to coincide with cross-hair labels on a target positioner box.
      Setups utilizing an immobilization mask were verified by x-ray verification using
      ExacTrac and On Board Imaging, and if alignment were not within tolerance, then
      shifts were made using a 6D robotic couch. Gantry star-shot irradiation was
      performed using a 5mm cone to evaluate the differences between radiation
      isocenter and the target. The mean and standard deviations were calculated for
      differences in the x-, y-, and z-coordinate axes. RESULTS: Positional accuracy
      using ExacTrac for mask based SRS resulted in 1.10+/-0.86, 0.67+/-0.83, and
      0.59+/-0.48mm for cross plane, inline, and vertical measurements, respectively.
      Differences for frame based SRS were 0.93+/-0.43, 0.76+/-0.18, and 0.34+/-0.12mm
      for cross plane, inline, and vertical measurements, respectively. Results for
      mask based SRS using OBI will soon follow. CONCLUSIONS: Although the frame-based
      SRS techniquegenerated smaller standard deviations, the mean difference from
      target to radiation isocenter for both techniques fall within the statistical
      uncertainty of one another. Planning margins must take into account target size
      when treating small lesions for both techniques. Project funded by CARTI.

PMID- 28517196
TI  - SU-E-T-383: Pulsed Low Dose Rate Radiotherapy Using Advanced Treatment Methods: A
      Novel Technique for Patient Re-Irradiation.
AB  - PURPOSE: Pulsed low dose-rate radiotherapy (PLDR) re-irradiation has the
      potential to reduce late normal tissue toxicity while still providing significant
      tumor control for recurrent cancers. In contrast to conventional treatments
      delivered at dose-rates of 400-600cGy/min, PLDR treatments deliver 20cGy pulses
      separated by 3-minute intervals to achieve an effective-dose-rate of 6.7cGy/min.
      This work aims to investigate the planning strategy and delivery quality of PLDR
      treatment using IMRT and RapidArc techniques. METHODS: Twenty cases (10 treated
      with PLDR IMRT, 10 for evaluation purposes) were recruited in this study
      including prostate, pancreas, lung, head-and-neck, breast and pelvis. IMRT and
      the RapidArc treatment plans were generated using the Eclipse TPS. For IMRT
      treatment, each plan consisted of 10 fields to achieve a daily dose of 200cGy.
      The breast IMRT and the RapidArc plans consisted of two fields/arcs, respectively
      (40cGy/plan) and were delivered 5 times. The dose contribution from each field to
      the planning target volume (PTV) was analyzed to evaluate the feasibility for
      PLDR treatment. Machine-operation- dose-rate and plan quality was also
      investigated. Dose delivery accuracy was assessed using a cylindrical diode
      array. RESULTS: Throughout the six treatment sites, the mean PTV dose ranged from
      16.1 to 26.1cGy/arc for RapidArc plans and 10.3 to 36.7cGy/field for IMRT plans.
      For IMRT, the PTV dose contribution from each field strongly depends on the beam
      arrangement and optimization parameters. With very low dose for a full rotation
      (~ 20cGy/arc), the machine-operation-dose-rate of RapidArc plans significantly
      affects plan quality and deliverability. A machine-operation-dose-rate of 100
      MU/min results in superior delivery accuracy (>97.7% gamma-passing-rate for
      3%/3mm criteria) for both IMRT and RapidArc plans. CONCLUSIONS: PLDR radiotherapy
      using IMRT and RapidArc techniques Result in both dosimetric and radiobiological
      benefits, which may have great potential for those previously-irradiated patients
      who have historically done poorly.

PMID- 28517197
TI  - SU-E-T-427: Effect of Contrast in Radiadyne Alatus Balloon Packing System on
      Bladder and Rectal Doses in Gynecological Brachytherapy.
AB  - PURPOSE: Vaginal packing for gynecological brachytherapy is used to immobilize
      the applicator and reduce doses to the bladder and rectum by increasing the
      separation from the applicator. With the introduction of theRadiadyne AlatusTM
      balloon packing system, we evaluate further reductions in dose to these
      structures by increasing the concentration of contrast in the balloon, increasing
      its attenuation. This evaluation has been performed using the AcurosTM dose
      calculation algorithm. METHODS: A patient with cervical cancer was treated with
      HDR Ir-192 by insertion of a tandem and ovoid applicator, with the AlatusTM
      balloon system used for vaginal packing instead of wet gauze. The balloons were
      filled with distilled water containing 10% Omnipaque contrast. Retrospectively,
      the balloons were contoured in the BrachyVisionTM planning system, and the CT
      number of the structure set was adjusted to determine the effect of the
      concentration of the contrast in the balloons on bladder and rectal doses after
      heterogeneity correction using the AcurosTM algorithm. RESULTS: Use of 10%
      Omnipaque solution reduced the bladder and rectal point doses by 6% and 9.5%,
      respectively, with similar reductions in the D2cc and D1cc for each structure.
      Overriding the density of the balloon showed that a 50% solution would reduce the
      doses by 8% and 30%, respectively, due to the positions of the balloons with
      respect to the applicator dwell positions. CONCLUSIONS: Use of the AlatusTM
      balloon packing system allows reduction of the bladder and rectal doses both by
      increasing the distance between the bladder and rectum and the applicators and by
      increased attenuation of the dose by the use of contrast solution. Optimal
      dilution of the contrast should take into account both the positive protective
      effect of the solution as well as any negative artifact that the solution causes
      in the CT scan, which might obscure the patient's anatomy patient.

PMID- 28517198
TI  - SU-E-T-393: Using TG119 to Assess RapidArc at Hamad Medical Corporation.
AB  - PURPOSE: To provide a confidence level within our clinic relating to the
      implementation and administration of RapidArc, the AAPM TG1 19 has been
      implemented. This task group provides a sound and relatively simple methodology
      for determining the accuracy of the overall IMRT process administered in the day
      to-day clinicMethods: Six different test plans, of varying complexity, were
      created on mock structure sets, downloaded from AAPM, and delivered. The
      treatment planning system results were then compared with the delivered results.
      Plans were created and delivered on a solid water phantom, using 25*25cm water
      equivalent slabs of varying thicknesses. Delivered point and planar dose
      measurements were obtained using an ionization chamber and film, respectively.
      RESULTS: The confidence limit (CL), averaged for all test plans, was calculated
      for the high dose point in the PTV and for the low dose point in the avoidance
      structure. This was used as an indicator of the uncertainty of the average
      difference between measured and planned dose. Where the precision of the delivery
      is based on how small the CL value is.For both the high and low dose points, the
      local CL's were determined to be 0.036 and 0.011, respectively. The range of
      results for the CL presented in TG1 19 varies from 0.015 to 0.098 for the high
      dose point, and from 0.014 to 0.086 for the low dose point. CONCLUSIONS: Our
      results indicate the accurate implementation of RapidArc within our clinic,
      especially when compared to the results of other institutions, published in TG1
      19. Furthermore, the CL value for the low dose measurements is lower than any of
      the results published in TG119. We recommend that any clinic conducting IMRT
      should implement this task group. This will not only provide a greater
      understanding of the delivery and its limitations, but will also give the overall
      accuracy and consistency of the technique as it applies to the various treatment
      sites.

PMID- 28517199
TI  - SU-E-T-438: Optimal Proton Beam Energy to Treat Adult CNS, Adult Head and Neck,
      and Pediatric Cancers.
AB  - PURPOSE: Proton therapy machines with lower beam energy requirements are expected
      to be easier and more cost-efficient to design, construct, and operate,
      particularly when using novel proton acceleration technology (e.g., dielectric
      wall). We determine, for adult central nervous system (CNS) and head and neck
      (HN) and pediatric cases, the optimal proton beam energies that can lead to
      clinically acceptable plan quality. METHODS: Proton treatment plans for various
      adult CNS and HN and pediatric cases, previously treated at our institution using
      helical tomotherapy, were generated using a commercial planning system (XiO, v.
      4.62, Elekta) with a passively-scattered proton beam model. Proton beam
      orientations were chosen such that the distance from the skin to the distal
      target edge was minimal; however, beams could not pass through areas with
      significant surface irregularity (e.g. ear), nor through OARs with strict dose
      limitations (e.g. lens). For a given beam direction, the planning system would
      calculate an optimum range and modulation to cover a given target volume. Beam
      weights were adjusted so that 95% of the target volume received the prescribed
      dose. All plans were limited to two proton beams. RESULTS: An optimal proton
      energy exists for each case studied. Among all cases, target dose conformity (the
      ratio of target volume to volume encompassed by theprescribed dose) ranged from
      0.74 to 0.94, and target dose uniformity (the ratio of the D5 and D95 doses)
      ranged from 1.01 to 1.04, with the optimal proton energies. Among the CNS and HN
      cases and for most pediatric cases, the maximum proton energy required was 133
      MeV. For a pediatric abdomen case, 159 MeV protons were required. CONCLUSIONS:
      For protontreatment of most adult CNS and HN and pediatric cases, the optimal
      energies that are capable of generating good quality plans are only as high as
      130 MeV.

PMID- 28517200
TI  - SU-E-T-404: A Prototype Program for Analyzing 4D Image Guidance Shifts for Lung
      SBRT.
AB  - PURPOSE: A prototype in-house program was developed to assist deriving image
      guidance shifts clinically using our 4DCT method for lung SBRT. METHODS: Our in
      house prototype program was implemented in MATLAB. The 4D DICOM CT dataset of
      interest is imported by the program from AW and subsequently accepts input from
      the user regarding the desired relative IGRT shifts. The DICOM header information
      defining the relative 4D dataset origin is then read in and the desired relative
      IGRT shifts are applied to re-define the origin for the dataset that is to be
      shifted. Lastly, the redefined (shifted) origin coordinates are written to the
      header of the 4D dataset and the dataset is then exported to AW as DICOM files.
      We used this program to process 4DCT datasets for four patients with 3-5
      fractions each. The clinical shifts that were derived previously, without this
      program, were applied to the images and the acceptability of these shifts were
      evaluated. RESULTS: All slices and planes of the shifted 4D dataset were reviewed
      and, in general, demonstrated acceptable re-centering of the target within the
      ITV. However, it is noted that some small adjustments to the shift coordinates
      would likely have been made had we had the opportunity to visualize the shifted
      4D dataset as facilitated by the new in-house software. The additional
      adjustments for the four patient cases studied here had an average of lmm and
      maximum of 2mm in three principle directions. We look forward to exploring the
      potential for implementing this software into our clinical workflow, and we
      believe that such a workflow is worthy of consideration by vendors for
      implementation as an available feature in future versions of their software.
      CONCLUSIONS: We presented a prototype program to shift 4DCT image set for lung
      SBRT applications and demonstrated four clinical cases.

PMID- 28517201
TI  - SU-E-T-420: Development of a Comprehensive Linac-Based Quality Assurance
      Procedure for Retrofitted Micro-MLC SRS System.
AB  - PURPOSE: To develop a QA tool and methodology to be used with an Elekta SL 25
      Linear Accelerator retrofitted with a 3DLine Micro-MLC gantry attachment in a
      room installed with the 3DLine Dynatrac camera localization system Methods: A
      phantom wa manufactured from clear polyester casting resign. This phantom was
      designed to fit within the localizing head frame to test the accuracy of the
      3DLine camera system in terms of isocenter localization. The phantom was aligned
      using the imported isocenter coordinates from the ERGO++ TPS. The phantom
      consists of metallic wires intersecting at the center and extending outwards to
      the center of each of the six sides of the cube. Gafchromic film was taped to
      each side and the cube was irradiated at different gantry and couch angles to
      verify isocenter accuracy to within 1mm in accordance with TG 142. The films were
      analyzed with RIT113 software, using the 50% isodose curves as the field edges
      and the center of the field as marked by each of the wiresextending outwards from
      the isocenter. RESULTS: Prelimina ry results of this isocenter test with the
      retrofitted Micro-MLC gantry head attachment show a deviation of .72mm and -1.25
      in the * and y directions respectively for the 90 degrees  gantry angle. A
      deviation of -1.27mm and -2.35mm in the x and y directions, respectively were
      measured for the 270 degrees  gantry angle. The additional sides will be
      irradiated and their results along the results of the additional tests will be
      presented at the AAPM national conference. CONCLUSIONS: After successful
      completion of the above procedures for SRS QA, it was determined that the phantom
      made with the localization wires can indeed be used to accurately and efficiently
      QA a linac-based SRS system for isocenter location accuracy.

PMID- 28517202
TI  - SU-E-T-386: Gamma Analysis of Normalized and Un-Normalized Dose Distributions.
AB  - PURPOSE: The gamma index method, as currently implemented in all commercial QA
      software, calls for selection of a normalization point to evaluate agreement
      between two dose distributions. The implication of this is that there is an
      infinite number of possible solutions! Which one to pick? A unique and more
      relevant solution is obtained only if no normalization point is used. METHODS AND
      MATERIALS: The set of test cases suggested by the AAPM TG1 19 were planned using
      Pinnacle 8.0m and delivered on a Varian 21EX linac for 6 and 18 MV photons. The
      recommended point and planar dose measurements were obtained using a Pinpoint ion
      chamber, EDR2 film and MatriXX. The gamma index method using typical 3%, 3 mm
      criteria with and without a normalization point was used to assess the agreement
      between calculated and delivered planar dose distributions. The analysis was
      extended to a set of data for clinically treated patients. RESULTS: The
      comparison with the TG119 benchmark data showed that all point dose and planar
      measurements for 6 MV were within the published range. Similar results, although
      without published data to compare with, were obtained for 18 MV as well. For all
      complex tests, the percentage of points passing the gamma criteria of 3%, 3 mm
      was (95.8+/-1.6)% and (95.6+/-1.0)% for 6 MV and 18 MV, respectively. Without a
      normalization point, however, the same gamma analysis fell to (20.7+/-6.7)% and
      (13.9+/-4.0)% for 6 MV and 18 MV, respectively. The clinical data set showed the
      same trend, with the gamma passing rate declining from (98.9+/-0.7)% to (33.4+/
      13.1)%. CONCLUSION: The gamma index method provides a unique answer for gamma
      passing rate only without normalizing dose distributions to any particular point.
      The common gamma criteria of 3%, 3 mm, however, is a very poor metric in that
      case.

PMID- 28517203
TI  - SU-E-T-397: Interplay Effect of Gated Lung Stereotactic Body Radiotherapy with
      RapidArc Delivery.
AB  - PURPOSE: To investigate the dosimetric effect of intrafraction tumor motion
      during gated RapidArc Stereotactic Body Radiotherapy (SBRT) delivery. METHOD: The
      realtime tumor motion data were retrieved from 6 lung patients. Each of them
      received 3 fractions of stereotactic radiotherapy treatments with Cyberknife
      Synchrony. Phase gating through an external surrogate was simulated with a gating
      window of 5 mm. The resulting residual tumor motion curves during gating (beam
      on) were retrieved. RapidArc SBRT was planned on the platform of Varian Truebeam
      at 6 MV with 1400 MU/min. Planning target volume (PTV) was defined as physician
      contoured clinical target volume (CTV) surrounded by an isotropic 5 mm margin.
      Each patient was prescribed with 60Gy/3 fractions. The RA plan typically consists
      of 2 arcs; each contains 90-120 control points. An algorithm was developed to
      reconstruct the delivered dose with tumor motion. The MLC segment is assumed to
      move relatively to a static tumor. Each MLC control point, mainly the leaf
      position were modified according to the probability density function of tumor
      motion. The newly created MLC control points were written back to the treatment
      file in the dicom format which was subsequently imported to treatment planning
      system (Varian Eclipse) for dose recalculation. RESULTS: The magnitude of dose
      deviation with motion is consistent with the excursion of the residual tumor
      movement. Overall CTV coverage of the study group is barely affected owing to the
      5 mm margin. The fractional PTV dose coverage dropped by 4% at most and that from
      all fractions by 3%. An examination in the point dose shows an increase of 4% in
      the maximum dose and decrease of 10% for the minimum dose. CONCLUSION: With
      effective gating, interplay effect does not change the target coverage much
      during gated RapidArc SBRT. However it increases the dose nonuniformity inside
      target.

PMID- 28517204
TI  - SU-E-T-408: Enhancing Stereotactic Radiosurgery for Neovascular Age-Related
      Macular Degeneration, Using Gold Nanoparticles.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of
      irreversible vision loss for people over the age of 60 in the United States. In
      this study the dosimetric feasibility of using gold nanoparticles (AuNP) as
      radiosensitizers to enhance stereotactic radiosurgery for neovascular AMD is
      investigated. METHODS: Analytic calculations were carried out to estimate the
      nucleus dose enhancement factor (nDEF) due to photon-induced photo- /Auger
      electrons from AuNP targeting neovascular AMD endothelial cells (EC). The nDEF
      represents the ratio of the dose to the nucleus with and without the presence of
      AuNP. As in previous studies, the EC is modeled as a slab of 2 MUm (thickness) *
      10 MUm (length) * 10 MUm (width) containing a nucleus of 5 MUm diameter and
      thickness of 0.5 - 1 MUm. The targeted AuNP are attached to the exterior of the
      EC. The nDEF was calculated for a range of feasible AuNP local concentrations (1
      7 mg/g) using the clinically applicable 100 kVp x-rays employed by the IRayTM
      system (Oraya Therapeutics Inc. Newark, CA), with total filtration of 0.75 mm Al
      and 0.8 mm Be. For comparison the nDEF for other energies: 80 kVp, 90 kVp, 110
      kVp, and 120 kVp was also investigated. RESULTS: For 100 kVp x-rays, the results
      revealed nDEF values of 1.30 - 3.26 for the investigated concentration range of 1
      - 7 mg/g, respectively. In comparison, for the same concentration range, nDEF
      values of 1.32 - 3.40, 1.31-3.33, 1.29 - 3.19, 1.28 - 3.12 were calculated for 80
      kVp, 90 kVp, 110 kVp, and 120 kVp x-rays, respectively. CONCLUSIONS: The results
      predict substantial dose enhancement to the sensitive nucleus of neovascular
      endothelial cells, targeted by AuNP during kilovoltage stereotactic radiosurgery.
      This suggests that AuNP may be employed as radiosensitizers to enhance
      therapeutic efficacy during radiosurgery for neovascular AMD.

PMID- 28517205
TI  - SU-E-T-390: Monitorization of the Dynamic Multi-Leaf Collimator Performance Using
      Log Files - a Quality Assurance Tool for Intensity Modulated Radiotherapy.
AB  - PURPOSE: Commission baseline values of the multi-leaf collimator (MLC) using
      Varian's dynalog file viewer software (DFV) and establish tolerance levels to use
      as a periodic quality assurance tool in intensity modulated radiotherapy (IMRT).
      METHODS: A sliding window test was created to have all leafs moving at a constant
      high speed of 2.5cm/s. This test was performed for 100 days at gantry angles of 0
      degrees , 90 degrees  and 270 degrees  during the morning quality checks in an
      accelerator performing RapidArc treatments with a Millennium 120 MLC. The DFV was
      used to collect the percentage of counts in bins 1 (0.05mm) to 8 (deviations in
      steps of 0.5mm) and the root mean square error (RMS). These were analyzed
      statistically and a baseline value and tolerance levels were established.
      RESULTS: Results show that the greater percentage of counts is found at bin 4
      with an average of 97%. Bins 1 to 3 have less than 1 % and bin 5 presents an
      average of 1.7%. As for bin 6, the average was below 0.1%. Bins 7 and 8 presented
      no counts. When comparing the results of the different gantry angles, significant
      differences are only found in bin 4 and 5, with a better performance for the 0
      degrees  gantry. As for the RMS error, no difference was found between different
      carriages or gantry angles and the average value was 0.129. A tolerance level was
      established for bins that correspond to greater deviations - bins 5 to 8, with an
      upper limit equivalent to twice the standard deviation of each bin. CONCLUSIONS:
      With the introduction of IMRT, the MLC quality assurance became more extensive
      and thorough. However a quantitative analysis is often difficult to interpret and
      time consuming. The purposed method allows the monitorization of the stability
      and performance of the MLC in a quantitative and easy way.

PMID- 28517206
TI  - SU-E-T-411: Dosimetric Comparison Between Two Multileaf Collimator Systems for
      Stereotactic Radiosurgery and Radiotherapy.
AB  - PURPOSE: This aim of this study is to compare the dosimetric parameters of two
      multileaf collimator (MLC) systems: (1) the beam modulator (BM), which is the MLC
      commercial name for Elekta 'Synergy S' linear accelerator; and (2) Radionics
      micro-MLC (MMLC). METHODS: Dosimetric parameters of percentage depth dose (PDD),
      in-plane and cross-plane beam profile, penumbra, MLC leakage and transmission for
      a 6 MV photon beam with different field sizes and depths were measured using
      ionization chamber, film, solid water phantom and water tank. At the same time,
      the BM and MMLC were modeled using the BEAMnrc code and the above dosimetric
      parameters were calculated using Monte Carlo simulations. Energy fluence spectra
      for the two MLC were determined using the BEAMnrc and BEAMDP. RESULTS: We found
      that dosimetric parameters (PDD, beam profile, energy fluence spectra, leakage
      and transmission) of the two MLC were similar, except for penumbra. The leaf-side
      and leaf-end 20%-80% penumbras at 10 cm depth for a 10*10 cm2 field were 4.8 and
      5.1 mm for the MMLC and 5.3 mm and 6.3 mm for the BM, respectively. The maximum
      percentage of the leakage for the BM and MMLC are 1.3% and 1.2%, while the
      average percentage of leakage for the BM and MMLC are 0.9% and 1%. CONCLUSIONS:
      Based on their dosimetric characteristics for stereotactic radiosurgery and
      radiotherapy, it can be concluded that both the BM and MMLC can be used
      effectively, though the latter showed slightly sharper dose penumbra especially
      in the leaf-end direction. However, the BM has the advantages of producing
      considerably larger field at isocenter and having a greater isocenter clearance
      compared to the MMLC. The dosimetric data in this study should help radiotherapy
      staff to appreciate dependence of dosimetry on the MLC design and configuration
      for stereotactic radiosurgery and radiotherapy. Actual or potential conflicts of
      interest do not exist.

PMID- 28517207
TI  - SU-E-T-422: Lung SBRT Using Cyberknife: Technique and Treatment Outcome.
AB  - PURPOSE: At East Carolina University, we have been treating primary and secondary
      lung cancers with Cyberknife stereotactic body radiotherapy (CK- SBRT) since
      February 2009. Till October 2011, we have treated a total of 79 patients (83
      sites). In this study, we present our experience in CK-SBRT and clinical outcome
      of the treated patients. METHODS: Of the 79 patients, 43 were female; age of the
      whole patient population ranged 33.2-89.7yrs (median=73.2yrs). Patients treated
      for primary lung cancer (n=57) had severe chronic obstructive pulmonary disease
      (COPD) and were not surgical candidates. Cyberknife robotic system with tracking
      techniques (Synchrony=52, XsiteLung=22, XsightSpine=5) were used. Majority of the
      patient (n=52) had multiple gold fiducials placed (1-6 placed; 1-4 tracked per
      patient) either percutaneously or bronchoscopically. CT images were used for
      dosimetric planning, by medical physicists, using Cyberknife MultiPlan software.
      Prescription doses were 25Gy-55Gy in 3-5 fractions (mean=48.2Gy, median=50Gy);
      doses were prescribed mainly to 80% isodoseline (range=75-96%, mean=81.4%). PTV
      margin varied from 0-7mm (mean+/-SD=3.2+/-1.4mm), based on the tumor locations;
      breathing patterns and cancer type. Dosimetric coverage of GTV and PTV were
      (mean+/-SD): 97.8+/-5% and 94.7+/-6.9%, respectively. The treatment response was
      assessed using either a CT or a PET scan or both. RESULTS: The median follow up
      was 13.1months (range 0.3-31.9 months). Overall response rate was 98.8%
      (CR=73.5%). Local failure free survival at one year was 84% for primary (n=57),
      76% for recurrent (n=16) lung cancer and 100% for metastatic (n=10) tumors. The
      toxicity rate was low with one patient reported to have chest wall pain and one
      patient developed grade 3-4 radiation pneumonitis. CONCLUSIONS: In most of the
      cases tight PTV margins were used. Since the prescriptions were at 80% isodeose
      line with more than 94% PTV coverage, the treatment outcome appeared reasonable.
      Further study relating PTV margin, dosimetric coverage, and treatment outcome is
      in progress.

PMID- 28517208
TI  - SU-E-T-433: Pear-Shaped Based Dose Optimization for HDR Intracavitary
      Brachytherapy for Cervical Cancer Patients with Small Uterus.
AB  - PURPOSE: Currently, CT has been widely used for HDR planning as MRI is not widely
      available for tumor imaging. Conventional pear-shaped isodose distribution may
      not be discarded completely because of possible microscopic diseases into
      parametrium/uterus. For patients with small uterus, organs at risk (OARs) can
      fall inside 100% conventional pear-shaped isodose-line. This study compares two
      pear-shaped based dose optimization methods for OARs sparing. METHODS: Seven
      cervical cancer patients with small uterus were evaluated using 2 methods. For
      Method A, with conventional dwell-time loading, point A lateral distance was
      reduced until all OARs' D2cc were within the dose limits. For Method B, a
      reference target volume was generated using conventional pear-shaped 100% isodose
      surface. While isodose-line near the point A was adjusted for OARs sparing,
      isodose-line surrounding ovoids were optimized to match the reference target
      volume. For equivalent OAR sparing, 100% isodose-line width (lateral dimension)
      at 1 cm inferior to point A (-1 cm) and at across centers of ovoids (ovoid) were
      compared between the 2 methods. RESULTS: OARs fall inside conventional 100%
      isodose-line in all cases. Median position of hot spots was 0.2 cm (range -;1.2
      to 2.9 cm) superior to point A. Using Method A, point A lateral distance was
      adjusted to 1.4-1.7 cm for OARs sparing. Median width of 100% isodose-line was
      5.82 cm at ovoid level, and 4.50 cm at -1 cm level. At ovoid level, median width
      of 100% isodose-line was reduced by 9(8-13)% for Method A, and was unchanged for
      Method B. At -1 cm level, median width of 100% isodose-line was reduced by 19(2-
      33)% for Method A, and 11(0-15)% for Method B. CONCLUSIONS: for patients with
      small uterus, OARs are often fall inside 100% pear-s haped isodose-line near
      point A level. OARs can be spared without dramatically compromise treatment
      volume coverage around cervix using Method B.

PMID- 28517209
TI  - SU-E-T-415: Evaluation of the Effect of the Dose Buildup Region for Flattening
      Filter Free Beams in IMRT Plans of Lung and Sinuses.
AB  - PURPOSE: The surface and buildup dose is known to be greater for flattening
      filter-free (FFF) beams as compared to flattened beams. We compare the effect of
      this difference in the dose buildup region between the two beam modes, in the
      context of IMRT plans for the lung and sinuses. METHODS: IMRT plans are delivered
      using both the standard flattened beam mode (6X) and flattening-filter-free mode
      (6XFFF). We compare the dosimetric differences of these two modes, for IMRT
      treatments for the lung and sinuses. Radiochromic films and parallel-plate
      ionization chamber measurements were taken, and evaluated for the following field
      sizes: 2*2 cm2 , 3*3 cm2 , 5*5 cm2 , 8*8 cm2 , 10*10 cm2 , and 20*20 cm2 . We
      evaluated the area under the PDD curve (AUC) for the buildup region for both 6X
      and 6XFFF beams. Ten SBRT lung and five IMRT sinuses plans were generated using
      the EclipseTM planning system, commissioned with AAA. Plan evaluation involved
      the comparison of the isodose distributions between plans of the two delivery
      modes. RESULTS: For small field sizes, the dose in the buildup region is greater
      for FFF beam than for flattened beam. The percentage differences between 6XFFF
      and 6X flattened beams for the following field sizes (2*2 cm2 , 3*3 cm2 , 5*5 cm2
      , 8*8 cm2 , 10*10 cm2 , and 20*20 cm2 ) are 3.4%,2.2%, 7.2%, 4.9%, 0.9%, and 
      0.5%, respectively. Plan evaluation of the IMRT sinus cases found approximately
      3% higher maximum dose within the PTV for FFF plans. No observable differences
      were found between two types of SBRT lung plans. CONCLUSIONS: For small fields,
      the dose buildup region of FFF beam is slightly greater than that of flattened
      beams. This effect is more pronounced in IMRT sinus cases, leading to higher dose
      within the PTV. There was no difference in the SBRT lung plans between the two
      beam modes.

PMID- 28517210
TI  - SU-E-T-382: An Analysis of VMAT Monthly Quality Assurance.
AB  - PURPOSE: The purpose of this study is to quantify the change in monthly VMAT
      quality assurance (QA) and determine the tests to maintain consistent delivery
      with a baseline. METHODS: VMAT monthly QA has been performed for over 14 months
      on two Elekta Synergy LINACs. A baseline was established at acceptance and the
      monthly QA results were compared to those initial values. Films were used to test
      the dependence on varying dose rate, gantry speed, rotational direction, and MLC
      speed. These parameters were tested independently and then together in a test
      called the synchronicity test. Ion chamber readings test a DMLC field with a
      varying dose rate and MLC speed. Introducing intentional errors into the tested
      fields allowed the detectable limits of the QA to be determined. RESULTS: The
      monthly QA has consistently matched the baseline within a 3% dose limit on film.
      Analyzing the synchronicity film with a gamma test using a 5%/0.5mm tolerance
      showed a monthly pass rate of over 99%. The DMLC test has been identical for the
      entire course of VMAT QA. Furthermore, intentional changes in the MLC speed were
      noticed on the synchronicity test in the form of a smaller gamma pass rate as the
      MLC error was increased. CONCLUSIONS: There is a monthly agreement with all films
      testing individual parameters, ion chamber DMLC readings, as well as agreement
      with the synchronicity test. This collection of data has lead to the conclusion
      that only the synchronicity test and DMLC readings need to be performed on a
      monthly basis. If those tests fail, then individual parameters need to be tested
      to determine the singular cause of the error. Having a single test used as a red
      flag increases the efficiency of the monthly QA and is being implemented with an
      EPID to eliminate the use of film.

PMID- 28517212
TI  - SU-E-T-392: A Software Tool of Extracting Dose Plane for Tomotherapy Delivery QA.
AB  - PURPOSE: To develop a software tool to extract dose planes base on on the setup
      (red) laser positions for Tomotherapy delivery QA(DQA). METHODS: We have a
      develop a simple tool to simplify a time-consuming step for tomotherapy DQA. The
      DQA analysis tools in Tomotherapy software was useful for film dosimetry but not
      convenient for 2D-array QA devices. Current DQA software requires the user to
      perform alignments twice: one for setting DQA phantom and the other for
      extracting dose plane. These two steps can be simplified into one if both
      alignments are based on the central axis of the detector plane. Once the setup
      (red) lasers are set for DQA, the dose plane can be extracted from the dicom dose
      file and the dicom plan file automatically. An open source software was written
      in C using dicomtk library. The accuracy of the program has been tested by
      comparing the extracted dose plane to the same dose plane but extracted by the
      manual method. RESULTS: The maximum dose difference is 0.5% and the mean
      difference is 0.2%. The differences are probably due to the variation between two
      manual alignments. The software extracts 2D-dose plane in a simple and automatic
      way. This not only cuts workload but also reduce the degree of human error
      because only one manual alignment is needed. A copy of this open source software
      is available upon request. We also hope Tomotherapy provides similar function in
      future upgrade. CONCLUSIONS: A software tool has been developed to simplify
      Tomotherapy DQA procedure.

PMID- 28517211
TI  - SU-E-T-426: Comparison of HDR Brachytherapy for Cervix Cancer Using an Adaptive
      Simulated Annealing Program and Oncentra- for Simultaneously Integrated Boost.
AB  - PURPOSE: High dose rate (HDR) volumetric brachytherapy is an effective method of
      treating advanced cervix carcinoma. Local failure is associated with multiple
      factors including higher maximal standardized uptake value (SUV) values in
      fluorodeoxyglucose positron emission tomography (FDG- PET) scans. The purpose of
      this study is to evaluate the ability to simultaneously boost regions of high SUV
      values using an in-house adaptive simulated annealing (ASA) algorithm and the
      Oncentra(r) (Nucletron V.B., Veenendaal, The Netherlands) treatment planning
      system, thereby potentially improving local control. METHODS: Five cervix cancers
      were evaluated for brachytherapy treatment (tandem/ring and/or interstitial
      needles). MRI and PET images were obtained post-implant and fused with treatment
      planning CTs to define a high-risk (HR) CTV (cervix and tumor on MRI) and GTV
      (volume with >50% of the maximum SUV on PET). The prescribed dose was 5-6 Gy to
      the HR CTV and 7-9 Gy to the GTV. Treatment plans were first generated in
      Oncentra(r) with IPSA followed by manual graphic optimization by the physician.
      Plans were also independently optimized using the ASA program. The two plans were
      compared side by side and one was chosen for treatment. Dose-volume parameters
      including D90, V100 of targets, D2cc to the critical organs, and generalized
      equivalent uniform dose (gEUD) of all structures were compared between the ASA
      and the Oncentra plans. RESULTS: Both ASA and Oncentra plans were considered
      acceptable by the physician in four of five cases. Two ASA plans were chosen due
      to better critical organ sparing and tumor coverage. Two Oncentra plans were
      preferred because of lower doses to critical organs. One ASA plan was not
      accepted because of a higher bowel dose. CONCLUSIONS: Both ASA and Oncentra(r)
      planning methods produce acceptable treatment plans for optimized brachytherapy
      of cervix carcinoma. Continued studies are warranted to further determine the
      relative strength of each method. This study was supported in part by a research
      grant from Varian Medical System Inc.

PMID- 28517213
TI  - SU-E-T-437: Interfractional Dosimetric Verification of Lung Patients Treated by
      Passive Double Scattering Proton Radiotherapy.
AB  - PURPOSE: Proton radiotherapy, with the ability to confine the dose at desired
      depth, can potentially benefit lung tumor patients by significantly sparing the
      healthy lung tissue. However, the superior proton dose distribution could be
      affected by tumor shrinkage due to the quick response and by motion especially
      related to the respiration. Thus the treatment should be frequently verified and
      be adjusted accordingly if necessary to achieve the initial treatment goal.
      MATERIAL AND METHODS: A cohort of 20 patients were selected from lung patients
      treated with passive proton radiotherapy. All those patients were evaluated via
      4D-CT scans and found to have tumor motion less than 1 cm. The internal target
      volumes (ITV) were derived based on the full inspiration and expiration phases.
      The average of the 4D-CT scan, full inspiration and expiration phases were used
      for the initial treatment planning. The planning objective was 95% of the
      prescription dose to at least 95% volume of the ITV. Bi-weekly verification 4D-CT
      scans were performed to assess the robustness of the initial treatment plan and
      no replanning was required for target dose variations less then 3%. RESULTS:
      Compared with the initial treatment plan, the standard deviations of target
      coverage on inspiration, expiration, and average verification CT scans are within
      3% for all the patients, with the maximum difference up to 7%. No statistically
      significant differences were found among the initial and verification plans
      (p>0.1). The percentage deviations of OAR sparing were highly variable, e.g., up
      to 40% for mean lung dose, 100% for mean heart dose, 50% for max cord dose,
      particularly for OARs receiving small amount of doses. However, the absolute dose
      deviations are all with OAR's tolerance. CONCLUSION: Overall, the passive double
      scattering proton modality allows for robust proton treatment planning and
      delivery to treat the lung tumors with limited motion.

PMID- 28517214
TI  - SU-E-T-403: Delivery Efficiency of StereoArc Stereotactic Body Radiotherapy
      (SBRT).
AB  - PURPOSE: Traditional SBRT employs approximately 10 static beams with up to 20 Gy
      per fraction, requiring lengthy treatments which can be difficult for patients to
      tolerate, increasing the risk of movement, and causing discrepancies in the
      reproducibility of the breathing cycle. Commercial VMAT systems offer shorter
      treatment times with modulated beams; however, modulation is often not necessary
      or desired for small fields. Conformai arc therapy offers efficient beam
      delivery, but with only one aperture shape and constant beam weighting over all
      gantry angles. This study evaluates the efficiency of a new SBRT delivery Method:
      a conformai arc with multiple aperture shapes and variable dose rate. METHODS:
      Three clinical SBRT cases were chosen for this study. Each static field was
      converted into an arc segment to create a StereoArc plan. Gantry angle ranges
      were determined from the clinical monitor units, with the MU/degree chosen to
      maximize the dose rate. All segments were merged into a single arc with variable
      dose rate. Dose distributions from the StereoArc plans were compared to the
      clinical static field plans using Pinnacle. Delivery times were compared between
      the static SBRT plans, both with and without Beam Automation, and equivalent
      StereoArc plans. All plans were delivered on a Varian TrueBeam using a dose rate
      of 1000 MU/min. RESULTS: Dose differences between StereoArc and static plans were
      minimal. Delivery times for the static plans were 5-8 minutes, while delivery
      time with StereoArc was less than 3 minutes for all cases, which was equivalent
      to delivering the static plans with Beam Automation. CONCLUSIONS: Delivery
      efficiency was improved up to 60%: from 8 minutes for static fields, to less than
      3 minutes for StereoArc. StereoArc appears to be both an effective and efficient
      way of delivering SBRT for centers not wishing to modulate SBRT and without
      access to Beam Automation. This study is partially supported by NIH grant
      1R01CA133539-01A2.

PMID- 28517215
TI  - SU-E-T-419: MU Verification for Small Lesions in Lung SBRT.
AB  - PURPOSE: To determine if a secondary MU calculation can validate the treatment
      planning system MU calculation for objects less than 4cm in diameter in small
      field lung SBRT. To determine the small object modifier to better predict the
      correct MU. METHODS: Four polystyrene spheres were embedded into lung mimicking
      material. The sphere diameters are 4cm, 3cm, 2cm, and 1.2cm. The spheres are made
      up of two dome TLD-100 chip holders. Each TLD holder holds two 0.125' square *
      0.035' TLDs. The output (cGy/MU) was measured at the center of each sphere for
      three depth and effective depth combinations. The depth, effective depth, field
      size, and energy were kept constant. The effective depth was kept constant by
      adding tissue equivalent water to the top of the phantom as the sphere diameter
      got smaller. The three depths were 5cm, 10cm, and 15cm, with an effective depth
      of 5cm, 6cm, and 7cm, respectively. The collimator field size and the effective
      field size was 3cm * 3cm. The energy was 6MV. The measured results were compared
      with the output predicted by our treatment planning system. RESULTS: Dose
      measurements were made with both TLD and film and the results were averaged. The
      secondary MU calculation predicted that the output would be the same for each
      sphere. However, the measured output dropped as the sphere diameter got smaller,
      especially for the 1.2cm diameter sphere. The output dropped by 5% at a 10cm
      depth and by 9% at a depth of 15cm. CONCLUSIONS: Secondary MU calculations cannot
      reliably predict the MU's for small objects less than 3cm in diameter without
      modifiers. A modifier of 3% is needed for a 2cm sphere and 7% for a 1.2cm
      diameter sphere.

PMID- 28517216
TI  - SU-E-T-385: Accelerated Beam Delivery with MLC Gaps in IMRT Fields.
AB  - PURPOSE: By default, the 4-mm wide leaf-pairs of the Elekta Beam Modulator MLC
      not used for field shaping are moved to under the primary collimator to minimize
      the leakage dose. The trade-off is the increased beam delivery time in the case
      of IMRT. This study examines the dosimetric impact and improved delivery
      efficiency by allowing the unused leaf-pair as 2mm gap to stay within the PTV
      aperture during beam-on. METHODS: The capability of the treatment planning system
      (Pinnacle) in modeling the central and off-axis dose through 2mm MLC gaps,
      respectively, was investigated. EBT film measurement performed in a solid water
      phantom was compared with the computed dose. For two representative IMRT cases,
      the dosimetric features of treatment plans generated with and without MLC gaps in
      the field were compared. Similarly, the delivery times for 13 IMRT cases with and
      without MLC gaps were compared. RESULTS: The peak dose of the leaf gap computed
      with Pinnacle was dependent on dose grid resolution. The difference between a
      0.5mm and 2mm dose grid was about 16.5% for 6MV and 15MV beam respectively. Using
      a 0.5mm dose grid, the maximum difference between measured and calculated dose
      was < 1% for a central axis gap, and < 3% for an off-axis gap. The maximum dose
      through a 2mm*4mm leaf gap was estimated < 10cGy for a typical IMRT plan. DVH
      comparison showed an increase of target dose up to 2% for the IMRT plans with
      gap, with minimal dose change to all critical structures. For the 13 IMRT cases,
      the beam delivery times were reduced by 27+/-9.7%, from 8.7+/-4.5 minutes to
      6.5+/-4.0 minutes. CONCLUSIONS: The beam delivery is accelerated by utilizing
      minimal gaps in the IMRT fields. The increased dose to the target is acceptable
      and is minimal to all critical structures.

PMID- 28517217
TI  - SU-E-T-430: Evaluation of Inverse Optimization in Brachytherapy for Locally
      Advanced Cervix Cancer.
AB  - PURPOSE: Brachytherapy is a vital part of treating locally advanced cervix
      cancer. Point-based 2D treatment planning is conventionally used. New CT/MRI
      compatible applicators for HDR brachytherapy make 3D conformal planning possible.
      GEC-ESTRO endorsed the EMBRACE (intErnational study on MRI-guided BRachytherapy
      in locally Advanced CErvical cancer) protocol which recommends standard-plan
      based manual optimization over inverse optimization due to the concern of the
      uncertainty of high dose in targets and adjacent normal tissue. This study
      investigated the feasibility of inverse optimization planning. METHODS: Eight
      cervix cases using tandem/ring applicators +/- parametrial needles were
      evaluated. Both manually and inversely optimized 3D conformal plans using
      Oncentra(r) Brachy were generated for each case following EMBRACE guidelines.
      Planning time and DVH parameters including D90 and V100% for HR-CTV, D90 for IR
      CTV, D2cc for normal structures (bladder, rectum, sigmoid colon, and small bowel)
      were compared. Dose was reported in total EQD2 dose, assuming 45Gy in 25
      fractions external beam and 28Gy in 4 fractions HDR treatment. Prescription dose
      (PD) and PD*2 isodose volumes and V100% and V200% for normal tissue (excluding
      all contoured OARs) were compared to evaluate the high dose volumes. RESULTS: The
      average planning time was reduced by 55% with inverse planning. Target coverage
      between inverse and manual plans differed by <2% for HR-CTV (D90 and V100) and IR
      CTV (D90). Inverse planning reduced the D2cc for normal structures by 4.2%-5.7%
      and the V100% and V200% for normal tissue by 31% and 40%, respectively. For 7 of
      the 8 cases, small bowel was observed near the target and received significant
      dose with either approach. CONCLUSIONS: In this study, inverse planning improved
      DVH parameters over manual planning, with less planning time. Reporting normal
      tissue dose should alleviate the concern of undetected high dose regions. Even
      though small bowel is not often considered in traditional planning, dose should
      be reported.

PMID- 28517218
TI  - SU-E-T-396: Beam Angle Optimization for IMPT Comparing Gantries and Fixed Beam
      Lines.
AB  - PURPOSE: To explore the potential of beam angle optimization (BAO) for IMPT and
      compare fixed beamlines with gantries. METHODS: For three patients with
      challenging intracranial lesions, we generate reference IMPT treatment plans
      applying three manually selected beam orientations and treatment plans applying
      three optimized beam orientations considering five scenarios: (1) patients are in
      supine position and the treatment room features (1.a) a horizontal beamline,
      (1.b) a horizontal, 45 degrees , and vertical beamline, (1.c) a gantry, (2)
      patients are in supine or seated position and the treatment room features (2.a) a
      horizontal beamline, or (2.b) a horizontal, 45 degrees , and vertical beamline.
      We use a genetic algorithm that considers up to 1,400 non-coplanar candidate
      beams and evaluates 10,000 beam ensembles for one BAO. Beam orientations that may
      compromise the robustness of treatment plans are excluded before the optimization
      based on an objective measure of existing tissue heterogeneities. RESULTS: The
      optimized beam ensembles exhibit certain similarities even though the sets of
      candidate beams differ significantly for the five scenarios. Compared to manually
      selected beam orientations, they provide improved OAR sparing and equivalent
      target coverage. Compared to one another, they yield comparable target conformity
      (deviations of the conformity number <1%), target homogeneity (standard
      deviations of the target dose <0.8 Gy), and sparing of OARs (deviations of
      average mean and maximum doses in OARs +/- 1 Gy). Using a gantry, however, the
      integral dose can be reduced by 5-15% compared to a horizontal beamline with
      patients in supine position. For the investigated cases comparable reductions can
      be achieved by also irradiating in seated position with a horizontal, 45 degrees
      , and vertical beamline. CONCLUSIONS: BAO has the potential to provide beneficial
      IMPT treatment plans. Compared to fixed beamlines, gantries yield only modest
      effects regarding OAR sparing but may enable a significant reduction of integral
      dose for individual patients.

PMID- 28517219
TI  - SU-E-T-407: Freedom from Conventional: Application of RapidArc for SBRT Lung
      Treatments.
AB  - PURPOSE: Stereotactic body radiotherapy (SBRT) has been applied in treating early
      stage small lung lesions, delivering hypofractionated doses in a conformai
      manner. Studies have shown that SBRT has similar outcomes compared with surgery.
      Conventionally, SBRT lung treatments rely on utilization of multiple small,
      conformai, static fields in coplanar and non- coplanar arrangements. With the
      advent of RapidArc, it is important to evaluate the differences in dosimetry and
      delivery of conformai SBRT lung treatments for both conventional static field and
      VMAT techniques. METHODS: A retrospective study of 12 patients at our institution
      who have received SBRT for primary lung lesions was used to evaluate the
      application of RapidArc for such cases. Originally treated plans utilized eight
      to ten conformai static coplanar and non-coplanar fields. RapidArc plans were
      generated in Eclipse using single and multiple arc setups. RESULTS: As an
      ntensity-modulated modality, RapidArc provides greater freedom as compared to
      conventional static field delivery, as one can achieve dose uniformity throughout
      the PTV or replicate the dosimetry synonymous with conventional SBRT. RapidArc is
      capable of reproducing the high conformality achieved by conventional SBRT; dual
      arc plans, delivering uniform dose distributions, yielded an average CI100% of
      1.11 and D2cm maximum of 63% of the prescribed dose, compared to 1.33 and 77% (p-
      values of .002 and .005, respectively) for conventional SBRT. Application of a
      short, non-coplanar arc, in conjunction with dual coplanar arcs, improved sparing
      of OARs in direct proximity of the PTV at the expense of treatment time. RapidArc
      allows for faster treatment delivery; conventional SBRT delivery averages 13.7
      minutes at our institution, whereas coplanar dual arcs are estimated to average
      treatment durations of 4.2 minutes. CONCLUSIONS: RapidArc is capable of
      generating conformai dose distributions and sparing of OARs, allows greater
      freedom in plan optimization, and reduces treatment time significantly.

PMID- 28517220
TI  - SU-E-T-389: Accuracy of a VMAT Planning System for Head and Neck Radiotherapy.
AB  - PURPOSE: To determine the accuracy of VMAT treatment planning and delivery for
      patients undergoing radiotherapy in the head and neck. METHOD AND MATERIALS: A
      dosimetric study of a typical head and neck treatment plan has been carried out
      using Chamber, film and TLD's placed inside an anthropomorphic phantom. Lateral
      and AP port films were taken to verify the isocenter prior to treatment. Multiple
      treatments were performed to assess the reproducibility and uncertainty in the
      TLD measurements. Gafchromatic film was used between the phantom slices and then
      analyzed as an independent check on the TLD results. The two data sets, from TLDs
      and films, were then compared with the treatment planning system dose
      calculations. RESULTS: The measured dose to the primary planning tumor volume
      agrees with the planning system within 2%. The comparison of the measured dose to
      the secondary tumor volume ranges from 3-6% and the spinal cord comparison ranges
      from 3-10%. CONCLUSION: This new Smart Arc treatment, VMAT, has great benefits to
      the patient in that patient motion and internal motion of the tumor is
      dramatically reduced. Challenges arise in predicting the dose near
      heterogeneities between the treatment planning system and actual measurement.

PMID- 28517221
TI  - SU-E-T-400: SBRT Dose Verification Using Monte Carlo Simulation.
AB  - PURPOSE: To verify the SBRT plans on CMS Xio treatment planning system using the
      Monte Carlo simulation and investigate the related issues. METHODS: The SBRT
      plans with 6 MV were created on CMS Xio treatment planning system with
      superposition algorithm. The same patient's CT, beam geometry and MUs were used
      in the Monte Carlo simulation (MC) on MCSIM. MCSIM is an EGS4-based MC dose
      calculation system for photon and electron beams. The Monte Carlo plans were
      compared with the Xio plans to verify Xio superposition algorithm for SBRT. The
      electron disequilibrium was particularly investigated by comparing the DVHs for a
      2-mm thick peel of the GTV. The beam energy was changed from 6 MV to 10 MV for MC
      to test energy effect on SBRT dosimetry. RESULTS: Six SBRT lung plans created on
      Xio and delivered on Varian 21 EX linac were included in this study. The tumor
      GTV ranged from 1.4 cc to 11 cc and the dose ranged from 1950 cGy to 5400 cGy.
      The comparisons were made in terms of DVHs, mean doses, minimal doses, and
      maximal doses for GTV. The results showed all the dose values of Xio plans agreed
      with MC to within 2% with only two exceptions of 3% and 5%. The dose distribution
      in the peel of GTV followed the same pattern as the whole GTV. This indicated the
      Xio superposition algorithm has well accounted for electron disequilibrium. The
      10-MV beams had both hot and cold spots from DVH comparison. This may be due to
      the large build-up region for high energy beams. CONCLUSIONS: The Xio
      superposition algorithm has adequately accounted for electron disequilibrium and
      can perform accurate dose calculation for SBRT. Compared to high energy beams, 6
      MV is preferable in terms of the GTV coverage and dose homogeneity.

PMID- 28517222
TI  - SU-E-T-421: 6MV Radiation Small Field Dose: Off Axis and Penumbra Effects, a
      Study with Radiochromic Film.
AB  - PURPOSE: To accurately determine relative dose factor scaling, tissue depth
      relation, and penumbra details of small 6MV radiation fields with an emphasis on
      far-off-central-axis fields for various MLC designs -subject matter important in
      the context of SRS, FSRT, SBRT, and IMRT. METHODS: Radiochromic film designed for
      quantitative dosimetry, EBT3TM film (Ashland Inc.) can be reliably used as a
      relative dosimeter to within 1% accuracy if one controls for both film and
      flatbed scanner variation. This enabled a study of the fine detail of small
      radiation fields and the impact upon these small dose profiles by different MLC
      designs both on central axis and off. In particular, the impact of leaf-end
      penumbra from bifocal MLC Optifocus (Siemens) and Synergy Beam Modulator (Elekta)
      is examined.EBT3 films were placed at 100cm SAD in solid water phantom and
      irradiated to 200 MU at various depths 1.5cm - 20cm and for various off-axis
      locations. The films were analysed to give the detailed dosimetric profile of
      each small field and relate them to both a standard reference field (10 * 10)cm2
      and to a broadfield flatness/symmetry irradiation (20 * 20)cm2 . Films were
      scanned at ~20 hours post irradiation on an Epson 2000 flatbed scanner and
      analysed using FilmQAPro and in-house methods. RESULTS: As small field size
      decreases, the field center falls within the penumbra of each MLC edge for
      megavoltage photon energies. The penumbral effects cause the conventional
      dosimetric quantity SP to sharply depart from the smooth fieldsize dependence for
      larger conventional fields. CONCLUSIONS: Careful characterization of small field
      dose and leaf end modeling within a TPS is crucial in both predicting accurate
      small field dosimetry and off-axis dosimetry.

PMID- 28517223
TI  - SU-E-T-432: Comparison of HDR Treatment Plans for Interstitial Brachytherapy with
      Intracavitary Savi Brachytherapy for Post Lumpectomy Breast Cancer.
AB  - PURPOSE: To compare the dose distributions from HDR brachytherapy using
      interstitial catheter implants and Intracavitary Savi applicator for breast
      cancer patients following lumpectomy. METHODS: We have treated over 200 post
      lumpectomy breast patients with brachytherapy and Savi applicator (Cianna
      Medical) . The interstitial technique used a custom built template for placement
      of catheters under the image guidance. The Savi applicator was placed into the
      resected cavity and the applicator was expanded to cover the cavity under CT
      image guidance. The criteria used for plan evaluation was prescription dose
      covered 95 to 100% of the volume 1.5* prescribed dose to cover <30% of the PTV
      and 2.0 * prescribed dose covered <10% of the PTV. The Savi plans were evaluated
      with PTVeval to cover 90 to 95% of the prescribed dose and 1.5*PTVeval not to
      exceed 50cc, 2*PTVeval to cover <10% of volume. RESULTS: The PTV for interstitial
      ranged from 29 to 170cc, and that for Savi the PTVeval varied from 28 to 111. For
      interstitial the 1.5* dose reference expressed as % of PTV varied from 11% to 30%
      with a median at 24.9%. For Savi the 1.5* dose reference volume expressed as % of
      PTVeval ranged from 30 to 50% with a median of 40%. The 2* dose reference covered
      volume expressed as % of PTV varied from 5.5 to 30% of PTV at a median value of
      8.5%. The same for Savi varied from 13 to 31% at a median value of 19.4%. The
      skin dose for interstitial implant was less than 70% whereas same for Savi
      application was <100%Conclusions: We conclude that the dose uniformity for V1.5
      and V2 were better with interstitial implant as compared to Savi application.
      Also the interstitial implant allowed covering the desired margin of resection
      without restriction imposed due to air gap. Savi application, being less invasive
      was better preference by the patient over interstitial.

PMID- 28517224
TI  - SU-E-T-414: Clinical Implementation of Anthropomorphic Lung Phantom for Patient
      Specific SAbR QA.
AB  - PURPOSE: Dose calculations for lung stereotactic ablative radiotherapy (SAbR) are
      challenged by the presence of extremely heterogeneous tissue and small treatment
      volumes. In this work, an anthropomorphic chest phantom has been constructed for
      the purpose of commissioning treatment planning systems (TPS) and for patient
      specific SAbR QA. METHODS: A CT scan of a realistic chest phantom containing
      tissue equivalent materials for the spine, ribs, and lungs was imported into a
      Pinnacle TPS (CCC dose algorithm) where treatment plans were created for right
      and left-sided lung lesions. The phantom lungs are unique in that they contain
      embedded unit density spherical targets (2 and 4cm in diameter) that represent
      lung lesions. Plans directed to both tumors were designed for PTVs ranging from 2
      5cm in diameter using 6, 10, and 15MV beams while passing RTOG 0813 dose and
      conformality criteria. Each plan was then exported to an Eclipse TPS (AAA dose
      algorithm) for dose calculation. Plans were delivered with a TrueBeam LINAC
      corrected for machine output. Point dose measurementswere verified with a 0.015
      cc air ionization chamber placed in the center of each tumor. RESULTS: While the
      majority of plans developed in Pinnacle passed conformality criteria, the dose
      distribution as calculated in Eclipse failed to meet the RTOG guidelines,
      particularly for the small tumor at higher photon energies. All point dose
      measurements matched both TPS within 4%. Both TPS calculated a lower point dose
      than measured for large PTVs at all energies, improving as PTV size decreased.
      CONCLUSIONS: After comparing TPS and validating calculations with point dose
      measurements, the phantom was clinically implemented for patient-specific
      conformal SAbR QA.

PMID- 28517225
TI  - SU-E-T-425: Impact of Model Based Dose Calculation Algorithm for Ir-192
      Intracavitary Brachytherapy with Shielded Applicator.
AB  - PURPOSE: To determine the impact of a grid based Boltzmann solver (GBBS) on a
      cohort of cervical cancer patients treated with Ir-192 intracavitary
      brachytherapy with shielded applicators. METHODS: Retrospective plans were
      generated using BrachyVision v8.8 (TPS) with GBBS Acuros v1.3.1. The study
      includes 24 patients that had CT planning images acquired with CT/MR compatible
      applicators. Using the TPS applicator library, shielded colpostats and tandem
      (#AL13122005) were virtually positioned to replace the applicators seen on CT.
      Dwell weights were based on TG43 delivering 6 Gy to point A. Four GBBS
      calculations were performed to assess differences from the standard of practice
      TG43. The different GBBS calculations were: 1) no applicator modeled, body= 1
      g/cc muscle, 2) applicator modeled, body=1g/cc muscle, 3) applicator modeled, CT
      to-material mapping with contrast (vaginal packing, rectal, Foley balloon) =
      1g/cc muscle, and 4) applicator model, CT-to-material mapping without material
      overrides. The multiple GBBS calculations allow differences from TG43 to be
      attributed to factors representing the modeling of source and patient boundaries
      (scatter conditions), tissue heterogeneities, and applicators. RESULTS:
      Differences between GBBS4 and TG43 at clinical dosimetric points were as follows:
      [mean +/- standard (min, max)], Point A: - 2.5% +/- 0.5% (-3.8%, -1.2%), Point B:
      -1.5% +/- 1.0% (-3.2%, 1.1%), ICRU rectum: -8.4% +/- 2.5% (-14.0%, -4.1%), D2cc
      rectum: -6.2% +/- 2.6% (- 11.9%, -0.8%), ICRU bladder: -7.2% +/- 3.6% (-15.7%, 
      2.1%); D2cc bladder: -3.4% +/- 1.8% (-7.2%, -1.1%). Bar plots comparing the
      modeling factors previously listed show that applicator modeling is the largest
      contributor to differences from TG43. CONCLUSIONS: Clinically significant dose
      differences (>5%) relative to TG43 exist when using a model-based dose
      calculation algorithm such as the GBBS with shielded applicators. Differences
      were largely due to applicator modeling, not tissue heterogeneities, source
      modeling, or patient boundary modeling.

PMID- 28517226
TI  - SU-E-T-391: Modelling Peripheral Photon Dose in TomoTherapy Treatments.
AB  - PURPOSE: The delivery of the therapeutic radiation dose to the tumour in photon
      radiotherapy, also implies dose deposition in distant organs (peripheral dose)
      related to secondary cancers induction (Hall and Wuu, Int J Radiat Oncol Biol
      Phys 56:83-88, 2003). Therefore, peripheral dose estimation in MU-demanding
      techniques, such as Helical TomoTherapy (HT), becomes relevant. TLD measurements
      and Monte Carlo modelling were compared by D'Agostino (Strahlenther Onkol
      187:693, 2011). The purpose of this work was to find out experimental models
      predicting the equivalent photon dose as a function of the distance to the
      isocenter for different treatment types. The prostate case is presented here.
      METHODS: A HT prostate plan was delivered to an anthropomorphic phantom mimicking
      a male adult. The phantom was made of polyethylene blocks whereas light wood was
      used for lungs. 16 points distributed along the phantom, covering different
      depths, were selected (SA!nchez-Doblado IFMBE, World Congress Med Phys & Biomed
      Eng, 259-261, 2009). Additionally, a polyethylene sheet was inserted in the
      phantom to measure the off-axis dose profile at midplane depth. Measurements were
      carried out with standard TLD-100 pairs of dosimeters (calibrated in a 137Cs
      source). RESULTS: Two-exponential-terms curve fitting was carried out to model
      separately the scatter and leakage contribution (f=a*exp(-b*x)+c*exp(-d*x)). The
      former resulted predominant in the proximal region (10=x=14cm) and the latter in
      the distal re gion (x=14cm). Both components equate at 18cm. Scatter contribution
      becomes negligible for x=23cm. Points at 5cm were not used for the model as they
      are too close to the isocenter to be considered as peripheral dose. Model fits
      well experimental data (13% mean deviation). Only depths behind the build-up
      region could be properly modelled. CONCLUSIONS: Peripheral photon dose profiles
      in HT treatments have been modelled by a two-exponential-terms curve modelling
      separately scatter and leakage.

PMID- 28517227
TI  - SU-E-T-436: Feasibility of Using the 'Irregular Surface Compensator' Planning
      Feature of the Eclipse TPS for Total Body Irradiation (TBI) Treatment Planning.
AB  - PURPOSE: To investigate the feasibility of using the Irregular Surface
      Compensator (ISC) planning feature of the Eclipse treatment planning system (TPS)
      for Total Body Irradiation (TBI). METHODS: TBI treatments require that the whole
      body receives within +-10% of the prescribed dose. Different body parts with
      different thicknesses compared to the umbilicus separation may receive higher or
      lower doses compared to the prescribed dose. Another challenge is to keep the
      lung dose below 10Gy to avoid complications. To mitigate this problem, physical
      compensators and blocks are used during the treatment for different body parts
      and lungs. This method presents a challenge during the treatment delivery and
      prolongs the treatment time due to patient setup, in-vivo on-line dosimetric
      monitoring and the adjustment of the compensators frequently during the
      treatment. We investigated the use of ISC planning feature of Eclipse TPS which
      is an electronic compensation method that calculates a fluence map based on the
      body contour from the CT image. The fluence map is delivered with dynamic MLCs .
      This TBI treatment technique was tested using a Rando phantom in Head First
      Supine position with lateral beams at SSD=250cm.The calculated fluence were
      edited so that the lung received <~10Gy for 12Gy prescription. A single fraction
      of 2Gy was delivered and the in-vivo measurements were performed in the neck,
      lung and the umbilicus by using OSLDs. RESULTS: OSLD measurements and the Eclipse
      TPS predictionswere 200.4/195.0, 162.2/168.9, and 196.1/208.9 cGy for the neck,
      lung and the umbilicus respectively. CONCLUSIONS: The feasibility of using the
      'Irregular Surface Compensator' feature of Eclipse TPS for TBI treatment planning
      was demonstrated. Good agreement (<6%) between the predicted and measured doses
      was obtained. The proposed planning and delivery simplifies the compensation and
      blocking to achieve uniform dose distributions and reduces the treatment time.

PMID- 28517228
TI  - SU-E-T-402: Coordinate Transformation after Stereotactic Frame Reapplication in
      Gamma Knife Radiosurgery.
AB  - PURPOSE: In Gamma Knife (GK) radiosurgery, the occurrence of reapplying the
      stereotactic frame due to collision with the collimator leads to re- examination
      and re-planning. For the treatment of vascular lesions, it is a burden not only
      to physicians but also to patients to get invasive angiography procedure again.
      To avoid undergoing second angiography examination, and reduce re-planning time,
      a mathematical coordinate transformation method using the stereotactic images has
      been developed. METHODS: The MR or CT images of a patient brain before and after
      frame reapplication can be correlated with each other using the Affine
      transformation. The transformation parameters which minimize the RMS error of the
      original and transformed coordinates between the images were determined using a
      genetic algorithm. Three CT image studies of skull phantom were used for the
      verification of the algorithm. Moreover, five MR image studies of patients who
      underwent more than one GK procedure were used for the clinical evaluation. The
      coordinates under the original treatment plan were converted to new coordinates
      using the transformation matrix, and their dosimetric outcomes were compared.
      RESULTS: The RMS error in the coordinate transformation of skull phantom and
      clinical images was 0.3 mm and 0.6 mm, respectively. For total 9 treatment
      lesions of 0.2 ~14.1 cc, 3% and 11% RMS error in the irradiation time and target
      coverage were found respectively. The patients with only translational movement
      during the frame reapplication showed similar plan conversion results with the
      original plan. Also, deeply-located lesions showed a better RMS error of 3% in
      the conformity index than superficial lesions close to the skull. CONCLUSIONS:
      New treatment plans were obtained by applying the coordinate transformation to
      the original plans after the frame reapplication. The converted plans maintained
      the quality of the original plans with a little change in dose distribution
      arising from head rotation. This work was supported by a grant no. 04-2011
      0320110130 from the Seoul National University Hospital Research Fund and a
      National Research Foundation of Korea (NRFK) grant funded by the Korean
      government (MEST) (Grant No. K20901000001-09E0100-00110).

PMID- 28517229
TI  - SU-E-T-418: Evaluation of Peripheral Dose for SRS Treatment Radiations with the
      VIS CyberKnife: A Phantom Study.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) procedures are known to deliver a very
      high dose per fraction and thus, the increased risk of secondary types of cancer
      due to increased peripheral dose could be a limiting factor for the long term
      survival of the patients. The aim of this study is to evaluate the peripheral
      dose (PD) received at preselected anatomical sites in an anthropomorphic phantom
      for treatments of intracranial lesions with the CyberRnife. METHODS: Eight
      patients treated using the CyberRnife were selected for this study. Organs at
      risk and target were delineated on volumetric CT data and treatment planning
      (Multiplan v.4.5.0) was optimized accordingly, in order to achieve the required
      prescribed target dose and critical structures sparing for each patient. The
      final treatment plan was delivered with a CyberRnife VIS (Accuray, Inc.,
      Sunnyvale, CA) operating with a dose rate of 1000 MU/min at a flattening filter
      free mode and upgraded shielding. We performed our measurements using a male
      anthropomorphic RANDO phantom (Alderson Research Laboratories, Inc., Stamford,
      CT). Groups of three TLD 100 were placed anteriorly inside RANDO at a depth of 5
      cm at locations corresponding to the thyroid, breast or lung, uterus and inferior
      abdomen for each treatment plan. RESULTS: The average percentage dose normalized
      to the prescribed dose for the thyroid gland was 0.92+0.23 % with a max of 1.95%.
      The maximum reduction of the PD (expressed as percentage of the prescribed dose)
      was 80% between the thyroid gland and the lower pelvic area. Similarly the PD
      normalized to the number of MU showed an average of 0.84*10-3 (cGy/MU), with a
      max of 0.0025 (cGy/MU) for the thyroid gland region. CONCLUSIONS: It is evident
      that the PD is proportional to the number of MU as well as to the prescribed
      dose. These correlations can be utilized to estimate the PD during intracranial
      treatments.

PMID- 28517230
TI  - SU-E-T-429: Image-Guided Eye Plaque Brachytherapy Optimization: Implications for
      Patients at 2-Year Follow-up.
AB  - PURPOSE: Episcleral eye plaque brachytherapy has been utilized in the treatment
      of intra-ocular malignancies, delivering large prescription doses to the apex of
      the tumor. Advances in dose calculation and image guidance, via calibrated fundus
      images, enable localization of the tumor and determination of dose to the macula,
      optic disc, and lens. A two-year post-implant study aims to correlate dosimetry
      with local tumor control and changes in visual acuity, as well as assess the need
      for plaque optimization with respect to critical structures. METHODS: A
      retrospective, two-year follow-up study of 21 patients who have received
      episcleral eye plaque brachytherapy at our institution was used to correlate
      dosimetry with clinical outcomes and evaluate the need for eye plaque
      optimization. BEBIG Plaque Simulator wasused in treatment planning; fundus
      photographs were registered for tumor localization and the TG43-U1 formulism
      enabled dose calculation of I-125- loaded COMS plaques. Doses to the apex,
      macula, and optic disc were correlated to changes in apex height and visual
      acuity. Selected patients were replanned using optimization strategies to reduce
      dose to critical structures. RESULTS: A total of seven patients (33%) noted
      improved eyesight at two years. 11 (52%) patients lost at least two lines of
      vision at two years. Two patients saw increases in apical height (9%) within two
      years. Optimized eye plaque plans were able to reduce optic disc and macular
      doses (average 68Gy and 80Gy, respectively) by 36% and 25% on the average, while
      maintaining the prescribed dose. CONCLUSION: Image guidance and optimization are
      important tools that can aid in treatment of intra-ocular malignancies, as these
      techniques provide physicists with the ability to spare critical structures while
      delivering the prescription dose, thus increasing the possibility of local
      control and vision sparing.

PMID- 28517232
TI  - SU-E-T-440: Dosimetry Parameter Comparison between Field-In-Field Technique and
      Conventional Physical Wedge Technique for Whole Breast Radiation Treatment.
AB  - PURPOSE: To compare an advantage/disadvantage between Field-in-Field (FIF)
      technique and conventional physical wedge (PW) technique for a whole breast (WB)
      tangential field irradiation. METHODS AND MATERIALS: Total 86 patients were
      included in this study. 46 of them were left breast cancer cases. FIF/PW plans
      were created by Eclipse (V7.3, Varian) with 6MV or 6MV mixed with 18MV. Plans had
      a same ioscenter location, beam setup and normalized isodose line selection for
      each case. Varian 21EX Linac with 120 MLC was used for beam delivery. Two plans
      were compared by PTV encompassed by 95% isodose line (V95), dose inhomogeneity
      (DI), dose received by 10% volume of lung (D10), mean lung dose (MLD), dose
      received by 5% volume of heart (D5), Mean heart dose (MHD), total MU, maximum
      dose in the plan and the number of field needed for each fraction. RESULTS:
      Comparing with PW plan, FIF plan showed an average percentage improvement of V95
      was 0.1+/-1.6, DI was 0.6+/-5.0, MLD was 1.5+/-4.2, D5 was 2.0+/-8.8, MHD was
      3.2+/-4.6. However, D10 increased by 1.4%+/-0.050. FIF lowered an average daily
      MU by 28.5%+/-0.080, maximum dose by 0.5%+/-0.018, and increased number of
      treatment field by 1.50+/-0.356. There were 12 cases treated with mixed beam in
      PW technique vs 10 in FIF technique. CONCLUSION: The advantages of FIF technique
      included: (1) Reduce radiation contamination to contra lateral breast and Linac
      room induced activity by remove the PW, lower MU and diminish a higher energy.
      (2) Time saving was not only from less MU but also from not need go into the
      treatment room for a wedge adjustment. (3) Reduced the therapist work load. (4)
      Regular MU 2nd check was applied because there was not FIF merge involved in the
      treatment field. With a MLC to shape the field and treatment record/verification
      system to control the treatment, increasing number of treatment field didn't show
      as a problem.

PMID- 28517231
TI  - SU-E-T-395: Achievability and Optimization of Synchrotron-Based Respiratory Gated
      Spot Scanning Proton Beam Delivery.
AB  - PURPOSE: The purpose was to investigate the interplay of residual motion in
      realistically delivered respiratory gated spot scanning proton beam by a
      synchrotron. METHODS: A MatriXX 2D ion-chamber array detector was placed on a
      moving platform. The platform with the 2D ion-chamber array detector was moved
      based on sin4 motion with 3s and 5s cycle and 20 mm amplitude. Its motion was
      monitored by a laser displacement sensor (ZS-LDS2VT, omron, Japan). The
      respiration gate threshold level was set at 30% duty cycle and the residual
      motion within the gate window was approximately 6 mm. A 10*10 cm2 uniform field
      was delivered by a matrix of 13*13 spots with ~ 8 mm spot size (s) and 8 mm spot
      spacing. Measurements were done for the field delivered with a single painting
      and multiple re-painting, from 2 to 12 times, for both orthogonal and parallel
      scan directions. The same field was also measured without moving the detector,
      defined as the static reference dose. Dose homogeneity was compared between with
      gated and the static dose distributions. RESULTS: The worst single painting
      result of the dose homogeneity ratio was 0.90 in 3s motion cycle and 0.93 in 5s
      motion cycle with the orthogonal scan pattern, and 0.97 in 3s and 0.98 in 5s
      motion with the parallel scan pattern, respectively . The homogeneity ratio
      improved to over 0.98 by 4~6 times repainting in orthogonal and only 2 times re
      painting with the parallel scan. CONCLUSIONS: The respiratory gated spot scanning
      proton beam delivery is sensitive to spot movement direction relative to the
      residual motion of the target. A proper selection of the number of repainting and
      the scan direction can improve beam delivery quality. The study offers a basic
      understanding when implementing respiratory gated spot scanning proton beam
      treatment.

PMID- 28517233
TI  - SU-E-T-406: Online Image-Guidance for Prostate SBRT: Dosimetric Benefits and
      Margin Analysis.
AB  - PURPOSE: To evaluate the dosimetric benefits of online image guidance during
      prostate stereotactic body radiotherapy (SBRT) and the potential on margin
      reduction. METHODS: 28 prostate SBRT patients were retrospectively studied, each
      treated with 37Gy in 5 fractions. RTOG recently opened a similar protocol (0938).
      During treatments, per-beam couch corrections were made based on the actual
      target motion provided by dynamic tracking with either Calypso or per-beam OBI
      imaging. Dosimetric benefits of online correction were evaluated by comparing
      delivered dose distributions with and without such correction. The dose
      distribution without correction was generated in the same treatment planning
      system by accumulating doses without online correction from the each beam and
      each fraction. Quantitative analyses include the dosimetric difference between
      delivered doses with and without correction; the correction magnitude and
      frequency; and the potential on margin reduction based on the margin recipe by
      Van Herk et al. RESULTS: (1) Delivery without online correction results in small
      reduction on target mean dose (0.03+/-0.05Gy), maximal dose (0.01+/-0.06Gy), and
      conformity index (<0.06). (2) Delivery without online correction has small impact
      on OAR dose: 26 out of 28 patients have <1%/1.5cc differences in
      V18.5Gy/V24Gy/V28Gy/V33Gy/V37Gy for both the bladder and the rectum. Maximal
      differences are 4cc of the bladder and 1.6cc of the rectum in mid-dose regions
      (V18.5Gy). (3) For femoral heads, <1cc/1Gy differences are observed in
      V20Gy/Dmean/D1cc.(4) Average number of couch corrections per fraction is 0.49.
      The magnitudes are: (-0.2+/-2)mm vertically, (-0.1+/-2.1)mm longitudinally, and (
      0.2+/-1.4)mm laterally. (5) Margin determined by actual target motion in this
      patient population is 2.5mm isotropic. CONCLUSION: For both target coverage and
      OAR sparing, overall small benefit is seen from per-beam couch correction under
      dynamic tracking. The target motion between beams is small and random, and
      indicates a population-based margin size of 2.5mm.

PMID- 28517234
TI  - SU-E-T-388: Verification of Monitor Units and Dose Distributions in IMRT Plans
      Using Monte Carlo Algorithms on the E-IMRT Web Platform.
AB  - PURPOSE: Currently, quality control (QC) for each IMRT treatment is performed by
      dose distribution measurements. These techniques are very time-consuming and
      require long accelerator downtime. QC could be only based in verification of
      monitor units and dose distributions, if precise control of MLC is carried out.
      In such a manner, the e-IMRT platform (http://eimrt.cesga.es/) is a remote
      distributed computing tool, which allows comparison between the dose
      distributions calculated by a TPS and those calculated by Monte Carlo (MC).
      METHODS: Previously, our linear accelerator (Oncor Impression, Siemens) was
      commissioned. For this purpose, comparison of experimental and MC simulated data
      was carried out. Several IMRT treatments plans were calculated in superposition
      algorithm (TPS Xio(r)CMS 4.60.00) and used as input data for the e-IMRT platform.
      These treatment plans were previously verified employing a 2D array MapCheckTM,
      Sun Nuclear. The gamma index (3%, 3mm) was used for validating results. RESULTS:
      The platform displays calculated doses using MC, also gamma map (in the CT
      images, not only statistical data) and histogram shown in Figures 1a), b) and d).
      The gamma map illustrates the differences between the input and calculated doses.
      According to the legend in Figure 1 d), these differences correspond to less than
      1%. Results show good agreement between the doses calculated by TPS and those
      computed by e-IMRT platform. CONCLUSIONS: If a rigorous quality control is
      established for MLC and optimisation criteria (number of gantry angles, minimum
      segment size, levels of intensity for fluency map) are used. Then, QC for IMRT
      standard treatment plans would be only based on the verification of monitor units
      and dose distributions using e-IMRT II.This work has been funded by the Xunta de
      Galicia, Project R&D Grant 09SIN007CT. We would like to thank Centro de
      SupercomputaciA3 n de Galicia for the computational resources and support.

PMID- 28517235
TI  - New psychoactive substances: Purchasing and supply patterns in Australia.
AB  - OBJECTIVE: To examine the purchasing and supply patterns of new psychoactive
      substance (NPS) consumers in Australia. METHOD: Data were obtained from a self
      selected sample of 296 past-year NPS consumers, with comparisons made across
      dimethyltryptamine (n = 104), 2C-x (n = 59), NBOMe (n = 27), and synthetic
      cannabinoid (n = 22) users. RESULTS: Most consumers (58%) nominated a friend as
      their main NPS source, and almost half (46%) reported that they had supplied NPS
      to others in the past year (predominantly "social supply"). However, when
      comparisons were made across NPS, NBOMe users were more likely to nominate a
      dealer (30%) or online marketplace (22%) as their main source and to report:
      supplying NPS to others (63%); supplying to strangers (29%) and acquaintances
      (24%); and supplying NPS for cash profit (29%). Similarly, NPS consumers who
      nominated online markets as their main NPS source (9%; n = 26) were more likely
      to have supplied NPS to others (risk ratio [RR] 1.57); supplied to strangers (RR
      6.05) and acquaintances (RR 12.11); sold NPS for cash profit (RR 4.36); and to
      have exchanged NPS for something else (RR 3.27) than those who reported
      alternative primary sources. CONCLUSION: NBOMe consumers and those who nominated
      online markets as their main NPS source reported greater engagement with for
      profit supply; it is unclear if these individuals have "drifted" into dealing or
      if they were already engaged in such activities.

PMID- 28517236
TI  - Effect of centralization on long-term survival after resection of pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND: Centralization of pancreatic surgery has resulted in improved short
      term outcomes in a number of healthcare systems. The aim of this study was to see
      whether hospital volume influenced long-term prognosis, use of adjuvant therapy
      or histopathological evaluation of patients undergoing surgical resection for
      pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical
      resection of PDAC in Finland between 2002 and 2008 were identified from national
      registers. Demographic, histopathological, operative and oncological data were
      recorded, and the histopathological slides of patients who survived for more than
      4 years were reviewed. Operative volume was defined according to the annual rate
      of pancreatoduodenectomy as: high-volume centres (HVCs; 20 or more resections per
      year), medium-volume centres (MVCs; 6-19 resection annually) and low-volume
      centres (LVCs; 5 or fewer resections annually). RESULTS: Some 467 patients who
      had undergone resectional surgery for PDAC at 22 centres were included. Patient
      demographics and resection types did not differ between centres. Thirty- and 90
      day mortality rates were significantly lower in HVCs compared with LVCs: 0 versus
      5.5 per cent (P = 0.001) and 2.5 versus 11.0 per cent (P = 0.003) respectively.
      Tumours in HVCs were generally at a more advanced stage than those in LVCs (stage
      IIB: 65.7 versus 40.6 per cent respectively; P < 0.001), but with no greater use
      of adjuvant therapy. Significantly more patients survived for 2 years (43.3
      versus 29.7 per cent; P = 0.034) and 3 years (25.4 versus 14.1 per cent; P =
      0.045) after surgery in HVCs than in LVCs. More information was missing in the
      histopathological reports from LVCs and MVCs than in those from HVCs (P <=
      0.002). CONCLUSION: Both short- and long-term survival was significantly better
      for patients operated on in HVCs. Histopathological analysis appears to be more
      comprehensive in HVCs.

PMID- 28517237
TI  - Development of an alginate hydrogel to deliver aqueous bait for pest ant
      management.
AB  - BACKGROUND: Insecticide sprays used for ant control cause environmental
      contamination. Liquid bait is a safe and effective alternative, but it requires
      bait stations to dispense the toxicant. We developed a biodegradable hydrogel to
      deliver liquid bait obviating the need for bait stations. RESULTS: Alginate
      hydrogel beads with preferred rigidity and maximum hydration in 25% sucrose
      solution were engineered by optimizing a crosslinking process. The moisture
      content of the substrate on which the beads were placed and the relative
      atmospheric humidity significantly influenced water loss dynamics of the hydrated
      hydrogel beads. Laboratory choice studies indicated that hydrated hydrogel beads
      had reduced palatability to foraging ants when they lost >=50% water. An enzyme
      linked immunosorbent assay (ELISA) indicated that the insecticide thiamethoxam
      added to sucrose solution was absorbed into the hydrogel beads. Hydrogel beads
      conditioned in sucrose solution with 1 mg L-1 thiamethoxam provided complete
      control of all castes of Argentine ant Linepithema humile (Mayr) colony by 14
      days post treatment in the laboratory trial and provided a 79% reduction in ant
      activity after 8 weeks in the field trial. CONCLUSION: Alginate hydrogel beads
      provided an effective delivery system for liquid baits laced with low
      concentrations of insecticide to control Argentine ants. (c) 2017 Society of
      Chemical Industry.

PMID- 28517238
TI  - FleN and FleQ play a synergistic role in regulating lapA and bcs operons in
      Pseudomonas putida KT2440.
AB  - FleN generally functions as an antagonist of FleQ in regulating flagellar genes
      and biofilm matrix related genes in Pseudomonas aeruginosa. Here, we found that
      in Pseudomonas putida KT2440, FleN and FleQ play a synergistic role in regulating
      two biofilm matrix coding operons, lapA and bcs. FleN deletion decreased the
      transcription of lapA and increased the transcription of bcs operon, and the same
      trend was observed in fleQ deletion mutant before. In vitro experiments showed
      that FleN promoted the binding of FleQ to the lapA/bcs promoter DNA especially in
      the presence of ATP. Both phenotype observation and transcription analysis showed
      that, similar to fleQ deletion, fleN deletion significantly weaken the effect of
      high c-di-GMP level on biofilm formation, surface winkle phenotype and expression
      of lapA and bcs operons. Mutagenesis of the putative ATP binding motif in
      FleNK21Q revealed that FleN ATPase activity played an essential role in the
      regulation of flagellar number and swimming motility but was not critical for
      biofilm formation. Our results revealed that FleN was not an antagonist of FleQ
      but a synergistic factor of FleQ in regulating the two biofilm matrix coding
      operons in P. putida KT2440.

PMID- 28517239
TI  - The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort
      study.
AB  - OBJECTIVE: Our aim is to study the relationship between dose of baclofen and
      effectiveness in alcohol dependence. METHODS: Two hundred two patients with
      alcohol dependence, who received baclofen treatment for drinking reduction, were
      followed up for 1 year. For each patient-month of treatment, the maximum daily
      dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were
      calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for
      at least 2 consecutive months. We divided the DDB of each patient-month into 3
      categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150
      mg/d) and investigated the relationship between reaching a favorable outcome and
      the concurrent DDB category in a time-varying Cox regression analysis. Hazard
      ratios (HRs) were adjusted based on age, sex, and initial AWAC. RESULTS: One
      hundred forty subjects were followed during at least 1 month. Of these patients,
      58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose
      was associated with a decreased rate of favorable drinking outcome (HR = 0.42;
      95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31;
      95% CI [0.65, 2.64]). CONCLUSION: The relationship between dose of baclofen and
      favorable drinking outcome was U-shaped, that is, was increased at low and high
      doses compared to medium doses.

PMID- 28517240
TI  - Imaging after treatment in uterine malignancies: Spectrum of normal findings and
      most common complications.
AB  - Uterine malignancies account for the majority of gynaecologic cancers. Different
      treatment options are available depending on histology, disease grade and stage.
      Hysterectomy is the most frequent surgical procedure. Chemotherapy and radiation
      therapy (CRT) represents the preferred therapeutic choice for locally advanced
      uterine and cervical malignancies. Imaging of the female pelvis following these
      treatments is particularly challenging due to alteration of the normal anatomy.
      Radiologists should be familiar with both the expected post-treatment imaging
      findings and the imaging features of possible complications to make the correct
      interpretation and avoid possible pitfalls. The purpose of this review is to show
      the expected computed tomography (CT) and Magnetic Resonance Imaging (MRI)
      appearances of the female pelvis following surgery and CRT for uterine and
      cervical cancer, to illustrate the imaging findings of early and delayed most
      common complications after surgery and CRT, describing the suitable imaging
      modalities and protocols for evaluation of patients treated for gynaecologic
      malignancies.

PMID- 28517241
TI  - Dopant-Free Hole-Transport Materials Based on Methoxytriphenylamine-Substituted
      Indacenodithienothiophene for Solution-Processed Perovskite Solar Cells.
AB  - Solution-processed hole transporting materials (HTMs) that are dopant-free show
      promise for use in low-cost, high-performance perovskite solar cells (PSCs). The
      highest-efficiency PSCs use organic HTMs, many of which have low mobilities and
      therefore require doping, which lowers the device stability. Additionally, these
      materials are not easily scaled because they often require complicated synthesis.
      Two new HTMs (IDT-TPA and IDTT-TPA) were synthesized, which contained either an
      extended fused-ring indacenodithiophene (IDT) or indacenodithienothiophene (IDTT)
      core and strong electron-donating methoxytriphenylamine (TPA) groups as the end
      capping units. The extended conjugation in the backbone of IDTT-TPA resulted in
      stronger pi-pi interactions (3.321 A) and a higher hole mobility of 6.46*10-4 
      cm2  V-1  s-1 when compared with that of IDT-TPA (9.53*10-5  cm2  V-1  s-1 ). A
      dopant-free, planar PSC that contained IDTT-TPA was fabricated and exhibited a
      high power conversion efficiency (PCE) of 15.7 %. This cell exhibited a higher
      PCE and less hysteresis than devices that contained IDT-TPA.

PMID- 28517243
TI  - Sarcopenia is a risk factor for falling in independently living Japanese older
      adults: A 2-year prospective cohort study of the GAINA study.
AB  - AIM: The purpose of the present study was to investigate whether sarcopenia was
      associated with future falls in the general Japanese older population. METHODS:
      This study was a 2-year prospective observational study. Participants were
      recruited from individuals who had an annual town-sponsored medical check-up and
      had not received nursing care. The inclusion criteria for participants in our
      study were: (i) agreement to participate; (ii) living independently; and (iii)
      the ability to walk to where the survey was carried out and to provide self
      reported data. A total of 223 residents (82 men, 141 women) participated in the
      baseline assessment in the study. Demographic information, previous fall history,
      locomotive syndrome, body function and structural measurements and pain at the
      knee and/or lumber spine were assessed. The Asian Working Group for Sarcopenia
      algorithm was used to classify the presence of sarcopenia, and assess the history
      of falling when the participant received their annual medical check-up. RESULTS:
      A total of 162 participants had an annual follow-up assessment, 50 of whom
      (30.8%) fell at least once during the 2-year observational period after baseline
      assessment. Previous falling history, prevalence of locomotive syndrome,
      sarcopenia and pain were significantly higher in participants who had fallen
      compared with participants who had not. Multiple logistic regression analysis
      showed the prevalence of sarcopenia was a significant predictor of falling.
      CONCLUSION: The key finding of the present study suggests that sarcopenia is a
      risk factor for falling in older adults who are living independently even after
      adjustment for previous falls and confounding factors. Geriatr Gerontol Int 2017;
      17: 2124-2130.

PMID- 28517242
TI  - Race/ethnicity is associated with ABO-nonidentical liver transplantation in the
      United States.
AB  - United Network for Organ Sharing (UNOS) policies allow for ABO-nonidentical liver
      transplantation (LT) in candidates with Model for End-Stage Liver Disease (MELD)
      scores greater than 30. Previous studies showed ABO-nonidentical LT resulted in
      an 18% and 55% net gain in livers for B and AB candidates. These results
      suggested that the current liver ABO allocation policies may need refinement.
      There are, however, strong associations between ABO blood groups and
      race/ethnicity. We hypothesized that race/ethnicity is associated with ABO
      nonidentical LT and that this is primarily influenced by recipient ABO status. We
      examined non-status 1 adult candidates registered between July 1, 2013, and
      December 31, 2015. There were 27 835 candidates (70% non-Hispanic White, 15%
      Hispanic, 9% Black, 4% Asian, 1% Other/Multiracial). A total of 11 369 underwent
      deceased donor LT: 93% ABO identical, 6% ABO compatible, and 1% ABO incompatible.
      Black and Asian race/ethnicity were associated with increased likelihoods of ABO
      nonidentical LT. Adjustment for disease etiology, listing MELD, transplant center
      volume, and UNOS region did not alter this association. Stepwise inclusion of
      recipient ABO status did eliminate this significant association of race/ethnicity
      with ABO-nonidentical LT. Blacks and Asians may be advantaged by ABO-nonidentical
      LT, and we suspect that changes to the existing policies may disproportionately
      impact these groups.

PMID- 28517245
TI  - SU-E-T-312: Optically Stimulated Luminescent Dosimeter Performance in High Dose
      Rate Brachytherapy.
AB  - PURPOSE: To investigate the use of optically stimulated luminescent dosimeters
      (OSLDs) for high dose rate (HDR) Ir-192 brachytherapy. While common in
      megavoltage radiotherapy applications, the performance of OSLDs using kilovoltage
      energies, high dose gradient and high dose rate regions ubiquitous to HDR has not
      been demonstrated. METHODS: Commercially available nanoDotTM (Landauer, Glenwood,
      IL) OSLDs - 5mm diameter and 0.2mm thickness - were irradiated using an Ir-192
      source in various geometries to determine dose rate dependence. Angular
      geometries were created using a circular applicator designed for accelerated
      partial breast irradiation by Accuboost(r). RESULTS: Response remained linear for
      high doses and was independent of dose rate. Specifically, the OSLDs were shown
      to be linear with dose up to 200 cGy then became slightly supra-linear up to 600
      cGy. There was a slight angular dependence for OSLDs which becomes significant in
      'edge-on' scenarios. An asymmetry in this angular dependence was discovered, but
      was attributed to cable curvature, point source approximation, and positioning
      within its plastic casing. CONCLUSIONS: Clinical HDR doses of 300 cGy fall within
      the linear, dose-rate-independent region. Angular independence can be maintained
      by avoiding extreme 'edge-on' measurement geometries. Because of re- readability,
      OSLDs can serve as a permanent record or alternatively be annealed within a few
      hours using conventional fluorescent light. Lastly, OSLDs are produced for only
      $5 each. Due to these features, in conjunction with the dosimetric performance,
      OSLDs should be considered a reliable tool for in vivo HDR brachytherapy
      measurements.

PMID- 28517244
TI  - SU-E-T-290: Dosimetric Verification of Helical Tomotherapy against Experimental
      Measurements for Head and Neck Treatments.
AB  - PURPOSE: To verify a Tomotherapy plan for a typical head and neck treatment
      against experimental measurements. METHODS: The treatment plan for a head and
      neck case was generated by the Tomotherapy treatment planning system (TPS) to
      deliver ~70 Gy in 33 sessions to the contoured PTV. The plan was calculated on a
      CIRS ATOM anthropomorphic phantom that provides a grid spacing of 3*3 cm2 holes
      to accommodate thermoluminescent detectors (TLD). The plan was verified against
      experimental measurements carried out by 7 LiF:Mg,Ti (TLD-700) TLD. Up to 20
      locations were selected within the irradiated region and three detectors were
      used simultaneously at each point to decrease the statistical uncertainty. TLD
      locations were labeled in the planning system and dose comparisons between TPS
      prediction and experimental measurements were performed in terms of absolute dose
      to water for a single fraction. We examined the dose from (i) the corresponding
      3.5MV Tomo-scan alone and (ii) the complete treatment. TLD-700 were found to
      fulfill the requirements of reproducibility, linearity and flat energy response
      in a previous study. In particular, TLD energy response was previously checked
      for 6 MV flattening filter free and conventional radiation beams under reference
      conditions. RESULTS: Doses derived from the TPS were in most cases in good
      agreement (4% on average) with TLD dose measurements within TLD statistical
      uncertainties (about 3%). Larger discrepancies up to 7% were found for points
      close to complex tissue inhomogeneities, such as bony structures. Dose from the
      scanning procedure alone is about 1 % of the dose per fraction. CONCLUSIONS: This
      work indicates that dose delivery plans created with Tomotherapy TPS are accurate
      for head and neck tumor localizations.

PMID- 28517246
TI  - SU-E-T-295: Factors Affecting Accuracy in Proton Therapy.
AB  - PURPOSE: To examine the various processes involved and to assess their effects on
      the accuracy in proton therapy. METHODS: Proton therapy involved several
      processes: (1) Beam commissioning. (2) CT scan of patient. (3) Contouring. (4)
      Treatment planning. (5) Output factor measurements for each field. (6) Patient
      setup verification with image guidance. (7) Dose delivery. (8) Neutron dose and
      proton RBE at the distal edge. Within each step, there are several sub-processes
      that each may contribute to the uncertainty in the treatment. By analyzing each
      of the subprocesseswithin each process, based on measurements or published data,
      we estimated a % uncertainty to each sub-process and/or a distance uncertainty
      (in millimeter) on the proton range. A total uncertainty in proton therapy is
      estimated. RESULTS: The uncertainties assessed for the various processes are :
      (1) +/-1.5%; (4) +/-3.0%, and 1-3mm; (5) +/-2.0%; (6) +/-2 mm; (7) +/-2.0%, +/
      2mm. The uncertainties in (2) CT, (3) contouring and neutron dose in (8) strongly
      depend on the location and type of the tumor. On the other hand, the proton RBE
      at the distal edge in (9) is still debatable and may affect the dose uncertainty
      from 0-20% depending on which value we want to accept. Thus the overall
      uncertainty in proton therapy is at least +/-4.5% and +/-4 mm (by adding the
      various uncertainties in quadrature), without consideration of processes (2), (3)
      and (8), and the RBE effect. CONCLUSIONS: Due to the complexity in proton therapy
      and the various factors that may affect the accuracy in proton therapy, it is far
      more complicated to assess the accuracy in proton therapy. Our preliminary study
      showed that the accuracy in proton therapy is at least +/- 4.5% in dose delivered
      to a tumor with an uncertainty of +/-4mm to the distal edge of the SOBP.

PMID- 28517247
TI  - SU-E-T-315: Planning and Verification of CT-Based HDR Intraluminal Brachytherapy
      Treatment for Malignant Obstructive Jaundice.
AB  - PURPOSE: To present our experience using CT to plan and verify intraluminal HDR
      treatment for a patient with obstructive jaundice. Due to the obstruction's
      proximity to the small bowel, along with small bowel adhesions from past surgical
      history, it was imperative to verify source position relative to the bowel before
      each treatment. METHODS: Treatment was administered to a total dose of 2000cGy in
      5 fractions via a 6F intraluminal catheter inserted into the patient's 14F
      percutaneous drainage catheter. Graduations on the intraluminal catheter were
      used to measure the exact length of catheter inserted in to the patient's
      drainage tube allowing reproducibility. Dummy seeds inserted during CT were
      identified by iteratively aligning the planning system's 3D reconstruction axis
      to the catheter at multiple points as it snaked through the liver. Taking in to
      account the known offset between actual dwell positions and dummy source
      positions, we determined what dwell positions to activate for planning. CT
      verification was performed prior to each treatment to insure that the drainage
      catheter had not moved and that the distance from treatment site to small bowel
      was adequate. Dummy seeds and anatomical landmarks were identified on the scout
      image and correlated to the CT. RESULTS: Verification CTs showed remarkable
      consistency in the day-to-day drainage catheter position. The physician was able
      to easily identify the small bowel of concern on the CT and determine if a safe
      distance existed for treatment. CONCLUSIONS: The method outlined in this work
      provides a safe means by which to treat bile duct obstructions using HDR when
      critical structures are nearby. We were prepared to make real-time adjustments to
      our treatment plan to account for significant variation, but found it unnecessary
      to do so in this particular case.

PMID- 28517249
TI  - SU-E-T-318: Source Position Localization for ICBT Tandem & Ovoid Applicators
      Utilizing Oncentra Brachy Applicator Modeling.
AB  - PURPOSE: Nucletron's Oncentra Brachy Applicator Modeling plugin (AMp) may
      facilitate HDR cervical brachytherapy treatment planning when image artifact
      inhibits dwell position localization. The AMp utilizes a 3D CAD rendering of the
      corresponding applicator to define possible source dwell positions. This study
      compares the equivalence of source localization within a CT/MR Fletcher-type
      tandem and ovoid applicator utilizing clinical practice and Oncentra's AMp in a
      water phantom containing OAR surrogate structures. METHODS: KVCT image sets were
      acquired of a water phantom containing bladder and rectum surrogates as well as
      an assembled Nucletron Fletcher CT/MR applicator with various ovoid sizes (20,
      25, 30mm) and a 30 degrees  tandem. Using Oncentra's Brachy TPS, OAR-surrogates
      were segmented and catheters were reconstructed using (1) clinical protocols
      (i.e. using source dwell position markers) and (2) using the AMp. Treatment plans
      were generated following clinical protocol, ensuring 600cGy to the ICRU 38
      defined Point A. The center coordinates of each active dwell position were
      spatially compared. The dosimetric impact of these differences was quantified by
      determining D0. 1cc, D1cc and D2cc for the surrogate OARs. RESULTS: Preliminary
      results obtained for the 25mm ovoid / 30 degrees  tandem applicator show 80% of
      dwell positions defined by clinical protocol and the AMp agree within 1mm with a
      maximum deviation of 1.17mm. Differences in source positions resulted in an
      increase of 2.9%, 0.48% and 0.3% and 0.66%, 0.87%, and 0.59% for D0.1cc, D1cc and
      D2cc for the bladder- and rectum-surrogates, respectively, when utilizing the AMp
      rather than clinical protocol for source position localization. CONCLUSIONS:
      Preliminary results indicate that source dwell position localization utilizing
      Nucletron's Applicator Modeling plugin and our clinical protocol results in
      equivalent dosimetry for the simple, water phantom geometry investigated.
      Currently we are investigating the validity of this conclusion utilizing ovoids
      of different sizes as well as a CT/MR-compatible vaginal cylinder.

PMID- 28517248
TI  - SU-E-T-292: New Technique for Developing Proton Range Compensator Using Three
      Dimensional Printer.
AB  - PURPOSE: A new system for manufacturing proton range compensator (PRC) was
      developed by using a three-dimensional printer (3DP). The physical accuracy and
      dosimetrical characteristics of the new PRC (PRC-3DP) was compared with
      conventional PRC (PRC-CMM) manufactured by computerized milling machine (CMM).
      METHODS: A PRC for brain cancer treatment, with passive scattered proton beam,
      was calculated in the TPS (Eclipse, Varian, USA) and its data was converted into
      a new format for 3DP (Projet HD3000, 3D Systems, USA), using the in-house
      developed software. PRC-3DP was printed with UV curable acrylic plastic, while
      PRC- CMM was milled into PMMA using a CMM (V-CNC500, CINCINNATI, USA). We
      measured the 5 randomly selected points for its physical thickness of both PRCs
      to evaluate its physical accuracy. Stopping power ratio (SPR), spread-out bragg
      peak (SOBP, 90~90%) and distal fall-off (DFO, 20~80%) at the central axis, +2.5,
      and 2.5 cm in the lateral direction, and FWHM of dose profile in depth 6, 8, and
      10 cm were measured to evaluate for its dosimetrical characteristics. All
      measured data was compared with TPS data. RESULTS: There was no significant
      difference in the physical depths between the calculated and the measured value
      of both RPC-3DP and RPC-CMM (p<0.05). SPR of both PRC showed similarity in value
      (1.022) when compared with that of the water. Average difference of SOBP between
      the TPS and the measured data from both PRC was 0.3773+/-0.0075 and 0.2762+/
      0.0235 cm, while DFO was 0.06+/-0.005 and 0.0471+/-0.0042 cm, respectively.
      Average differences of FWHM between the TPS and the measured data from PRC-3DP
      and PRC-CMM were 0.1799+/-0.025 and 0.137+/-0.0181 cm, respectively. There was no
      significant difference in dosimetrical characteristic between the RTP and both
      PRCs (p<0.05). CONCLUSIONS: Physical accuracy and dosimetrical characteristics of
      the PRC-3DP were comparable to that of the conventional PRC-CMM, while
      significant system minimization was provided. This work was supported by the
      Technology Innovation Program, 10040362, Development of an integrated management
      solution for radiation therapy funded by the Ministry of Knowledge Economy (MKE,
      Korea). This idea was applied for a Korea patent (no. 10-2012-0010812).

PMID- 28517250
TI  - SU-E-T-264: New Concrete Designed and Evaluation for Megavoltage X Radiotherapy
      Facilities (CONTEK-RFH2).
AB  - PURPOSE: The most common material for shielding is concrete, which can be made
      using various materials of different densities as aggregates. New techniques in
      radiotherapy, as IMRT and VMAT, require more monitor units and it is important to
      develop specifically designed shielding materials. METHODS: Arraela S.L. has
      developed new concrete (CONTEK(r)-RFH2), which is made from an arid with a high
      percentage in iron (> 60%), and using the suitable sieve size, enables optimum
      compaction of the material and a high mass density, about 4.1-4.2 g/cm3 .
      Moreover, aluminate cement, used as base, gives high resistance to high
      temperatures what makes this product be structurally resistant to temperatures up
      to 1200  degrees  C. The measurements were made in a LINAC Elekta SL18 to
      energies 6MV and 15 MV with a field size of 10*10 cm2 for concrete samples in the
      form of tile 25cm*25cm with variable thickness. RESULTS: The linear attenuation
      coefficient, MUm, was determined for each energy by fitting the data to Eq. 1,
      where Xxm is the exposure in air behind a thickness xm of the material, and X0 is
      the exposure in the absence of shielding. These results are compared with the
      ordinary concrete (2.35 g cm-3) for 6MV and 15MV energies (Ref. NCRP Report
      No.151). Results are tabulated in Table1. Results of attenuation are compared
      with ordinary concrete in Fig. 1. CONCLUSIONS: The new concrete CONTEK(r)-RFH2
      increases photon attenuation and reduces the size of a shielded wall. A very high
      percentage in iron and a suitablesieve size approximately double the density of
      ordinary concrete. High mass attenuation coefficient makes this concrete an
      extremely desirable material for use in radiation facilities as shielding
      material for photon beam, and for upgrading facilities designed for less energy
      or less workload.

PMID- 28517251
TI  - SU-E-T-274: Monte Carlo Simulations of Output Factors for a Small Animal
      Irradiator.
AB  - PURPOSE: Measurement of dosimetric parameters of small photon beams, with field
      sizes as small 1 mm in diameter, is particularly challenging. This work utilizes
      Monte Carlo techniques to calculate percent depth dose (PDD) and output factors
      for small photon fields from a kV x-ray based small animal irradiator. METHODS:
      Absolute dose calibration of a commercial small animal stereotactic irradiator
      (XRAD225, Precision X-ray) was performed in accordance with the recommendations
      of AAPM TG-61 protocol. Both in-air and in-water calibrations were performed at a
      30.4 cm source-to-surface distance (SSD) for a reference collimator 50 mm in
      diameter. The BEAM/EGS was used to model 225 kV photon beams used for most
      therapeutic applications. The Monte Carlo model was provided good agreement with
      measured beam characteristics, e.g. PDD and off-axis ratios. Subsequently, output
      factors for various square and circular applicators were measured using an
      ionization chamber and radiochromic film, and compared with MC simulations.
      Directional Bremsstrahlung splitting (DBS) was utilized for variance reduction to
      improve efficiency of the output factor simulations. The statistical uncertainty
      on the MC- calculated results is between 0.5% and 1% for most points. RESULTS:
      The absolute dose measured for reference collimator at 30.4 cm SSD in water and
      in air is 4.1 and 4.12 Gy/min. The agreement between simulated and measured
      output factors was excellent, ranging from 1% to 2.84%. The MC- simulated and
      measured depth dose data, normalized at the surface, show excellent agreement,
      with a maximum deviation is approximately 2.5 %. CONCLUSIONS: Monte Carlo
      simulation provides an indispensible tool for validating measurements of the
      smallest field sizes used in preclinical small animal irradiation.

PMID- 28517252
TI  - SU-E-T-298: Evaluation of the CNAO Spot Scanning Technique Based on the First
      Clinical Deliveries.
AB  - PURPOSE: The first Italian hospital-based facility for hadrontherapy is the
      Centro Nazionale di Adroterapia Oncologica (CNAO) which started the clinical
      activity on September 2011 with protons beams. The control of the treatment is
      performed online by the Dose Delivery (DD) system which guides the whole
      treatment by measuring beam characteristics as number of delivered particles and
      beam position. The author will present the comparison between the required and
      delivered quantities. METHODS: The CNAO facility is based on a synchrotron
      designed to accelerate and deliver proton and carbon ion beams in the clinical
      ranges. Unlike most of the proton-therapy centres, the delivery technique adopted
      at CNAO is the "quasi-discrete" active scanning where dedicated magnets are used
      to drive a pencil beam through the target and the beam is normally not switched
      off during the transition between adjacent spots. These operations are performed
      by the DD system which, based on the treatment planning and the online analysis
      of dedicated beam monitor chambers, drives the scanning magnets. Spot by spot the
      DD records data which allow the comparison between the measured number of
      particles and position and the prescription. RESULTS: The data collected by the
      dose delivery during the treatments were analyzed in detail, each treatment
      consisting in more than 30 identical fractions. This allows checking the
      stability and the accuracy of the CNAO delivery over identical spot sequences.
      The comparison between the measured number of particles, the measured position of
      each spot, and the corresponding prescribed quantities will be presented in
      detail. Critical points will be discussed together with the proposed improvement
      of the system. CONCLUSIONS: The results confirm the good performance of the CNAO
      beam delivery obtained during the commissioning phase.

PMID- 28517253
TI  - SU-E-T-285: Flatness as a Measure of Changes in Photon Energy for Megavoltage X-
      Ray Radiotherapy.
AB  - PURPOSE: To compare the sensitivity of flatness based energy metrics versus an
      attenuation based metric (percent depth dose) as a function of energy changes
      from the linac's nominal clinical energy. METHODS: Energy changes were
      accomplished by adjusting the bending magnet current (BMI) +/-15% away from the
      value used clinically. Two metrics for flatness, relative flatness in the central
      80% of the field (flatness) and average maximum dose along the diagonals
      normalized by central axis (CAX) dose (diagonal normalized flatness, DNF), were
      measured using a commercially available ion chamber array (IC profiler, Sun
      Nuclear, Melbourne FL). Percent depth dose was measured in water for depths of 5
      and 10 cm in 3*3 and 10*10 cm2 field sizes. RESULTS: The sensitivity of percent
      depth dose (PDD) and flatness to energy changes were smaller than changes in DNF.
      For 6X the changes in PDD were from -1+ to +3% and the changes in flatness were
      from -5% to +2% for energy changes of +/-15% from the nominal energy, for 18X the
      PDD changed from -0.5% to +2.5% and the flatness from -5% to +2% over this energy
      range. DNF changed from +12% to -8% for 6X and from +8% to -6% for 18X over a +/
      15% change from the nominal energy and showed a near linear correlation with
      energy. In addition DNF was the only metric that was found to be sensitive to
      both increases and reductions of energy for both the 6 and 18 MV beams.
      CONCLUSIONS: Diagonal normalizedflatness was found to be the most sensitive
      metric to energy changes for photon beams of 6 and 18 MV. The IC profiler allows
      this metric to be conveniently measured as part of routine linac quality
      assurance. Sun Nuclear Corporation provided the IC profiler.

PMID- 28517254
TI  - SU-E-T-307: Quantitative Assessment of the Source Attenuation for the New CT
      Compatible Titanium Fletcher-Suit-Delclos (FSD) Gynecologic Applicator.
AB  - PURPOSE: To quantify the effect of 192Ir source attenuation due to titanium
      material used in manufacturing the new CT-compatible FSD device during treatment
      delivery. METHODS: A typical cervical cancer treatment includes primary external
      beam followed by a course of HDR Intra-Cavitary brachytherapy using FSD
      applicator. A detailed geometry of the applicator obtained from the manufacturer
      is implemented using Monte Carlo (MC) simulation package MCNP5. The bending
      angles of tandem and colpostats are 150 and 1200 respectively. The source
      geometry is of the VariSource wire model VS2000. We assigned 8 dwell positions in
      the tandem and 4 dwell positions in each colpostat to calculate dose rate at
      reference points with and without titanium wall present in the simulation.
      RESULTS: Based on the MC computation, the titanium tube reduced the overall dose
      to point A by ~1.5%, with contributions varying for each dwell position. We also
      compare MC results with BrachyVision treatment planning system calculations. The
      clinically used algorithm is based on AAPM report TG-43, which calculates the
      dose without inhomogeneity correction. The latest Varian release of the planning
      software BrachyVision-Acuros has the updated algorithm capable of inhomogeneity
      corrected dose calculation. For this study a treatment plan is created based on
      the exact coordinates of the MC model and used to calculate dose at reference
      points. The dose to reference point A with BrachyVision traditional algorithm is
      in excellent agreement with the homogeneous MC model result. CONCLUSION: The
      attenuation due to Ti wall is ~1.5% at point A compared to ~5% using a non-CT
      compatible system. Comparative accuracy of the two treatment planning systems
      with MC, especially in their abilities to account for the source attenuation due
      to the applicator titanium walls will also be presented.

PMID- 28517255
TI  - SU-E-T-286: Verification of Treatment Delivery Monitor Unit (MU) Calculation and
      Dose Estimation of Bilateral Total Body Irradiation (TBI).
AB  - PURPOSE: TBI treatment delivery MU and patient dose estimation are calculated
      manually at our institution. This study was to verify the accuracyof MU
      calculation and dose estimation of bilateral TBI by application of tissue
      heterogeneity correction. METHODS: Twelve TBI patients were simulated from neck
      to thigh in bilateral TBI position. CT images were imported into the treatment
      planning system (Philips, Pinnacle3). Treatment dose was prescribed to the
      midpoint at the level of the umbilicus. Treatment distance was 519 cm. Both 6MV
      and 23 MV opposite lateral beams delivered 200 cGy to the dose prescription point
      with a 40 *40 cm2 field size and 45o collimator angle. A 1 cm thick spoiler was
      placed about 15 cm from patient skin. Adaptive convolution superposition with and
      without heterogeneity correction was used for calculation of MUs and doses at the
      midpoints of the shoulder, chest, abdomen, and pelvis. RESULTS: Monitor units
      calculated with heterogeneity correction were 1.1% and 0.9% smaller on average
      than those without heterogeneity correction for 6MV and 23MV beams respectively.
      The maximum deviations of MU were 3.8% and 2.8% smaller. Average percentage
      differences of point doses with and without heterogeneity corrections were -0.2%,
      17.0%, -0.3%, and -2.7% at the levels of shoulder, chest, abdomen, and pelvis for
      6MV beam and 0.4%, 11.0%, 0.2%, and -1.7% for 23MV beam. Discrepancy of doses to
      the points at the shoulder level varied from -6.8% to 8.9% for 6MV beam and from 
      1.6% to 5.1% for 23MV beam. CONCLUSIONS: Bilateral TBI MU calculation errors
      caused by ignoring tissue inhomogeneity would be less than 4% and 3% for 6MV and
      23 MV beam. Dose estimation is less accurate using 6MV beam and the inaccuracy
      could be more than 8% for shoulder midpoint and 4% for pelvis midpoint.

PMID- 28517256
TI  - SU-E-T-294: Maximizing the Availability of Positron Emitting Nuclei for Proton
      Therapy Verification Using Different Beam Irradiation Sequences.
AB  - PURPOSE: To demonstrate that the amount of nuclei available for post- irradiation
      proton treatment verification using positron emission tomography (PET) can be
      enhanced by reversing the beam delivery sequence in proton scanning beam
      irradiations. METHODS: A time-dependent analytical model is used to calculate the
      distributions of positron emitting nuclei for three different irradiation
      sequences: a scattered beam and a scanning beam in both the conventional
      sequence, distal edge first, and reverse sequence, distal edge last. The
      simulated geometry emulates reference dosimetry measurements conducted at the
      Paul Scherrer Institute (PSI). The reference measurements irradiate a 10 *10 cm2
      field, delivering about 1 Gy to a 10 cm wide spread-out Bragg peak (SOBP).
      Positron emitter availability with different beam sequence and imaging times and
      the impact of the different irradiation sequences on the statistical error on a
      range extrapolation were investigated. RESULTS: The ratio of the amount of
      positron emitters from the distal last beam sequence to that from the distal
      first sequence was 2.22 in the last centimeter of the SOBP. The comparison
      between distal last and a scattered beam gave a ratio of about 1.7 in the same
      region. In the distal last irradiation, more isotopes decay within a 120 second
      window, than in a 240 second window using a distal first irradiation. The
      statistical fluctuation on a range extrapolation was also smallest in the distal
      last beam sequence. CONCLUSIONS: We demonstrated the effect of the irradiation
      beam sequence on the isotope production relevant for the verification of proton
      spot scanning therapy with PET. The largest amount of isotopes is available by
      irradiating the distal edge last. This new beam sequence reduces the
      PETmeasurement time while still offering higher counts and accuracy compared with
      both the conventional beam sequence and the scattering method. This project was
      supported by JSPS Core-to-Core Program.

PMID- 28517257
TI  - SU-E-T-322: A Dosimetric Comparison of PBI Brachytherapy Techniques: SAVI,
      Contura, and Tube and Button Applicators.
AB  - PURPOSE: To evaluate the dosimetry of partial breast irradiation brachytherapy
      techniques using the Strut Adjusted Volume Implant (SAVI), Contura, and Tube and
      Button (T&B) applicators. METHODS: A total of 51 breast-cancer patients (23 SAVI,
      6 Contura, and 22 T&B) were treated. The target was delineated following NSABP B
      39 guidelines. 3D plans were optimized using the Inverse Planning Simulated
      Annealing algorithm to deliver 3.4 Gy per fraction to the target and minimize
      dose to organs at risk (OARs). Graphical optimization was then used to fine tune
      the final dose distribution. The minimum cavity-to-skin distance was measured.
      Target coverage (V90 and V95) and maximum dose (D0.1cc) to the OARs were
      evaluated. Dose homogeneity index (DHI = 1-V150/V100) was calculated. RESULTS:
      The average cavity-to-skin distances were 4.1 mm (0.5-9.6 mm, SAVI) and 11.7 mm
      (7.1-15.4 mm, Contura). The target-to-skin distance for the T&B cases was 8.7 mm
      (5.0-13.7 mm). The average V90 and V95 to the target were 96.8% and 94.5% (SAVI),
      97.0% and 93.0% (Contura), 98.6% and 97.3% (T&B). The mean D0.1cc to the skin,
      ribs, and lung was 91.5%, 58.8%, 44.5% (SAVI), 93.1%, 51.3%, 40.5% (Contura),
      69.1%, 41.5%, and 31.9% (T&B). The average V150 and V200 to the normal breast
      tissue were 30.4 cc and 14.9 cc (SAVI), 29.5 cc and 7.3 cc (Contura), 18.3 cc and
      7.1 cc (T&B). The average DHI for the SAVI, Contura, and T&B cases was 0.55 (0.50
      0.60), 0.70 (0.63-0.78), and 0.76 (0.74-0.79). CONCLUSIONS: All techniques
      provided clinically acceptable target coverage and dose to the OARs. The SAVI
      device provided a lower skin dose at close cavity-to-skin distances while
      providing excellent target coverage. However, the T&B and Contura applicators
      produced more homogeneous dose distribution (higher DHI) in the target than the
      SAVI. The correlations between dosimetric properties and follow-up mammogram
      results are under investigation.

PMID- 28517258
TI  - SU-E-T-268: Evaluation of Photoneutron Contamination in Elekta Synergy-S High
      Energy Linear Accelerator and Indigenous Novel Solution: The AIIMS Experience.
AB  - PURPOSE: The photoneutron contamination problem was encountered due to laminated
      barrier wall and short maze. The purpose of this study was to report our
      experience in evaluating the photoneutron contamination during radiation safety
      survey and solution. METHODS: The photoneutron contamination measurement was
      carried out in Elekta Synergy-S high-energylinear accelerator for 15MV beam. A NE
      Neutron survey meter and for photon, Victoreen and RADOS survey meters were used.
      The laminated barrier wall composed of 37cm steel with 30cm concrete both side
      and short maze length of 5 meter. During safety survey, higher photoneutron
      levels for 15MV X-rays at treatment room door found. The effect of photoneutron
      contamination as function of neutron shielding materials of wood, polyethylene
      and boron and thickness, distance, locations and directions to the control
      console at distance upto 7 meter were investigated for 4 gantry angles at
      locations of treatment room entry doors namely door1(A), door2(B), console(C),
      conduit (D) and above-ceiling(G) for 15MV. RESULTS: The initial safety survey
      showed that neutron level of 47mR/h and photon leakage of 3.2mR/hr at the
      treatment entry room door1. The neutron values could bring down to the level of
      acceptance at the treatment entry door2, but the photon values are not
      acceptable. Therefore, 30cm concrete wall block was made at the location of door2
      and another bend was taken. Finally, treatment entrance room door was made using
      3cm polyethylene neutron shielding materials in order to achieve the both neutron
      contamination and photon leakage within the acceptable levels. CONCLUSIONS: The
      neutron sliding-door is operated manually in finger-push by technologist for day
      to-day usage. This simple solution is cost effective and increases the patient
      throughput. This study underlines that one needs to take appropriate safety
      measures prior to facility design whenever the space constraints situations
      arises for high energy linear accelerator.

PMID- 28517259
TI  - SU-E-T-278: Study of MAGIC-F Gel and PENELOPE Code Simulation Response for
      Clinical Electron Beams.
AB  - PURPOSE: To evaluate the response of MAGIC-f gel through dose response curves,
      percentage depth dose (PDD) and beam profile for clinical electron beams.
      METHODS: Glass tubes (Vacutainer (r)), with 6 cm length and 0.5 cm radius, with
      MAGIC-f were positioned inside a water phantom to study the gel response with
      doses from 0.5 Gy to 20 Gy in electron beams of 6, 9 e 12 MeV. Glass tubes of 20
      cm length and 1 cm radius and PMMA phantoms of 10 * 5 * 5 cm3 were used to PDD
      and beam profiles determinations, respectively, with a maximum dose of 2 Gy to
      the gel. The samples were analyzed through magnetic resonance imaging (MRI) with
      a 3 T tomography using a head coil, multiple spin echo sequence with 16 echos, TE
      15ms and TR 4000ms. The MAGIC-f response was simulated with PENELOPE Monte Carlo
      code in the same geometry used in the irradiations. The results obtained with
      MAGIC-f and PENELOPE were compared with clinical data. RESULTS: Calibration
      curves for MAGIC-f showed a linear behavior, with correlation coefficient of
      0.99, for all energies. The PDD and beam profile curves obtained with MAGIC-f
      presented differences lower than 1.5% and 3.0%, respectively, when compared to
      clinical data. Results obtained by PENELOPE and clinical data showed differences
      up to 1.0% and 1.5%, respectively, for PDD and profile curves. CONCLUSIONS: The
      dosimetric parameters for electron beams obtained experimentally with MAGIC-f and
      with PENELOPE code showed similar results to the clinical data. From the results
      it can be inferred that MAGIC-f can be used as a complementary dosimetric tool
      for electron beams due to its characteristics of high spatial resolution and the
      ability to construct tridimensional dose distributions. Also PENELOPE can be used
      to study MAGIC-f gel response in electron beams.

PMID- 28517260
TI  - SU-E-T-300: Monte Carlo Simulation of Single-Plane Magnetically Focused Narrow
      Proton Beams.
AB  - : Purpose To investigate narrow, elongated magnetically focused proton beams and
      compare their properties with passively collimated beams using Monte Carlo
      simulation. METHODS: We performed Geant4 Monte Carlo simulations involving a
      single quadrapole focusing magnet, thereby creating a flattened beam with an
      elongated elliptical cross section. The parameters of the magnet were chosen to
      mimic k=3 (quadrapole) Halbach cylinders that are available commercially as
      assemblies of rare earth permanent magnetic materials. For comparison,
      simulations were also performed with the same beam line components and passively
      collimated beams (using an elliptically shaped collimator). To facilitate fair
      comparison, efforts were made to closely match the planned treatment volumes
      (PTV) for each simulation case in dose, volume, and major and minor diameters of
      the elliptically shaped PTV at Bragg depth. RESULTS: Magnetic focusing delivered
      significantly better dose localization to the target over collimated beams which
      are the current beam delivery modality. Compared to collimated beams, the
      magnetically focused beams showed a 31% smaller therapeutic ratio, a 31% smaller
      integrated dose, a 34% smaller entrance dose, a 30% larger peak-to-entrance
      central depth dose ratio, a 37% smaller penumbra volume, and were 35% more
      efficient in dose delivery (based on proton number). CONCLUSIONS: The clinically
      relevant advantages of the magnetically focused beams compared to the collimated
      beams (the current standard of care) can be attributed to the preferential
      directional acceleration of protons due to the magnetic field. Our simulations
      suggest such magnets can be used to deliver tissue sparing doses to normal and at
      risk tissue, and enhanced dose to elongated, narrow targets. Future work to
      characterize and test prototype magnets is in progress. Such beams my find
      application in novel proton treatments including application to the spinal cord.

PMID- 28517261
TI  - SU-E-T-289: On the Use of a Diode Array for the Commissioning of Dynamically
      Wedged Asymmetric Fields Generated by Varian EDW's in the Pinnacle Treatment
      Planning System.
AB  - PURPOSE: To present a validation study of enhanced dynamic wedges (EDWs)
      implemented into Pinnacle3 treatment planning system (TPS) using a diode array,
      Monte Carlo (MC) simulation, and measurements. METHOD AND MATERIALS: Modeling of
      EDW dose distribution in the Pinnacle3 TPS is based on a combination of open
      field beam data and the Varian 'Golden Segmented Treatment Table' (GSTT) unique
      to each photon beam. To validate the EDW models, dose profiles of 6- and 10-MV
      photon beams from a Clinac 2100C/D were measured in virtual water at depths from
      near- surface to 30 cm for a wide range of asymmetric field sizes and wedge
      angles using the Profiler-2 diode array system. The EDW output factors for
      asymmetric fields were measured in solid water using a small-volume cylindrical
      ionization chamber placed at a depth of 10 cm on the central axis. In addition,
      absolute doses on central axis at depths of 5, 10, 15 and 20 cm were measured in
      virtual water using a small-volume cylindrical chamber for comparison with the
      collapsed-cone convolution (CCC) calculations. The 6- and 10-MV photon beams
      emerging from the treatment head of the Clinac 2100C/D were fully simulated using
      the Monte Carlo code BEAMnrc and DOSXYZnrc. This code was used to calculate the
      central-axis percentage depth doses and dose profiles for the open and
      dynamically-wedged fields in a water phantom. RESULTS: The off-axis dose profiles
      of various EDWs computed with the CCC dose model and MC simulations agreed with
      measured EDW dose distributions to an accuracy of better than 2%/2 mm. Measured
      EDW output factors used for MU calculations in Pinnacle3 TPS agreed with MC
      predictions within 1-2%. CONCLUSIONS: The utility of Profiler-2 diode array
      system to measure dose profiles for commissioning of EDWs into the Pinnacle3 TPS
      has been demonstrated to have acceptable accuracy for clinical implementation.

PMID- 28517262
TI  - SU-E-T-311: Dose Perturbation Due to Thin Layers of High-Z in HDR Ir-192 Source
      Dose Delivery.
AB  - PURPOSE: To evaluate the dose perturbation associated with thin layers of high-Z
      materials in HDR 192I source dose delivery through Monte Carlo simulation and
      experimental measurement. METHODS: Dose perturbation of high-Z thin materials in
      HDR 192Ir source dose delivery was experimentally and theoretically studied.
      MCNP5 Monte Carlo simulation code was employed to calculate the dose enhancement
      effects at upstream and downstream of high-Z materials. The cutoff energy for
      photon was 1 keV and for electron 5 keV. A parallel plate ion chamber with window
      thickness of 0.9 mm, was used to measure the dose rates at the downstream of the
      high-Z thin layer. The high-Z layer was positioned at 0.625 cm from the 192Ir
      source. The thickness of layer was from 0.1 to 1 mm. The results were normalized
      by the dose rate in a homogeneous water phantom at the location of the interface.
      The high-Z materials used were lead, tin and titanium. In addition, the dose
      enhancement effects of different high-Z materials at the shortest distance from
      the interface were also calculated and measured to examine the Z dependence.
      RESULTS: The Monte Carlo simulation results agreed very well with the
      experimental data. At the surface of the 0.1 mm high-Z interface, Ti, Sn and Pb
      respectively increase dose rate by 1.2, 1.4 and 2.5 times the dose rate in
      homogeneous water medium. The dose rate enhancement depends on Z and thickness of
      the high-Z layer. The dose enhancement increases with Z. However, an increased
      thickness in the high- Z layer results in less dose enhancement due to
      attenuation. CONCLUSIONS: HDR 192Ir source dose enhancement by a high-Z material
      thin layer is similar to that reported from a kilo-voltage X-ray beam. Attention
      should be paid for high-Z thin layers with HDR source clinically as it could
      cause significant dose enhancement.

PMID- 28517263
TI  - SU-E-T-272: Commissioning an Orthovoltage Unit Used for Radiobiology Research.
AB  - PURPOSE: Orthovoltage X-ray units are used to irradiate cell cultures or small
      animals in research. Beam characteristics of these units are often not well
      understood and only nominal dose specified is used by researchers in their
      studies. This work describes commissioning of an orthovoltage unit similar to
      that of a linear accelerator. METHODS: The X-Rad 320 Orthovoltage unit is a self
      contained x-ray system which can be operatedwithin a wide range of kVp and mAs
      settings. This work characterizes the beam produced by this system. Various beam
      data, including depth dose, cross profiles, collimator and total scatter factors,
      have been measured. Collimator and total scatter measurements were done with
      cylindrical farmer chambers (0.6 cc and 0.057 cc volumes) for field sizes ranging
      from 2*2 to 20*20 cm2 . Sc measurements were done in air at 50 cm SCD and Sc,p
      measurements were done in 2 cm depth of phantom at 50 cm SSD.The depth dose
      curves were generated for three different field sizes for depths up to 15 cm. A
      parallel plate chamber was used for surface and near surface dose measurements
      while the cylindrical chamber was used for other depths. RESULTS: Measurements of
      Sc and Sc,p indicate minimal variation of these factors with field size, except
      for very small fields. The results of depth dose measurements produce results
      comparable with published data for similar beams and indicate a very small dose
      buildup at shallow depths. CONCLUSIONS: Proper characterization of an x-ray beam
      and accurate dosimetry is of importance in radiobiology investigations which may
      lead to advent of new therapies for humans. This work investigates the beam
      characteristics of an orthovoltage unit to ensure accurate irradiation of
      samples. The data collected here could further be used for simulation of dose
      distribution within irradiated volume.

PMID- 28517264
TI  - SU-E-T-314: Evaluation of Dosimetric Impact of Catheter-Position Uncertainty in
      Balloon High Dose Rate Brachytherapy of Breast Cancer.
AB  - PURPOSE: To evaluate the dosimetric impact of catheter-position uncertainty prior
      to each fraction in balloon high dose rate (HDR) brachytherapy for breast cancer.
      METHODS: For 30 balloon HDR patients, each dwell position of the catheters was
      manually shifted distally (+) and proximally (-) with a magnitude of +/-1 mm, +/
      2 mm, +/-3 mm and +/-4 mm. A total of 240 plans were retrospectively produced and
      compared to clinical treatment plans to simulate catheter-position uncertainty.
      The following dosimetric data were evaluated: PTV_EVAL V90[%] after subtracting
      air/seroma volume, skin and rib maximal dose (Dmax[%]) and normal breast tissue
      V200[cc]. RESULTS: PTV_EVAL V90 was decreased in 93% of cases while increased
      with maximum value of < 0.7% in 7% of cases. Average/maximal reduction was
      increased from 0.3%/1.2% (+/-1 mm), 1.0%/3.5% (+/-2 mm) and 2.6%/6.2% (+/-3 mm)
      to 5.0%/9.2% (+/- 4 mm) as catheter-position error was increased. Change of skin
      and rib Dmax values was case-specific. They were increased in 52% of cases while
      decreased in 48% of cases. As catheter-position error was increased, the
      average/maximal deviation was increased from 1.6%/9.3% (+/-1 mm), 3.1%/19.1% (+/
      2 mm) and 4.6%/29.1% (+/-3 mm) to 6.3%/40.2% (+/- 4 mm). Normal breast tissue
      V200 was increased in 90% of cases while decreased with maximum value of < 0.4cc
      in 10% of cases. Average/maximal increase was elevated from 0.3cc/1.2cc (+/-1
      mm), 0.8cc/2.9cc (+/-2 mm) and 1.8cc/4.8cc (+/-3 mm) to 2.9cc/6.7cc (+/- 4 mm) as
      catheter-position error was increased. CONCLUSIONS: The catheterposition
      tolerance of +/-2 mm set by the AAPM TG 56 is clinically acceptable for most
      clinical cases. However, in a case where the dosimetric data of treatment plan
      are close to the dosimetry limits of the clinical protocol, smaller tolerances
      such as +/-1 mm or zero tolerance is clinically recommended to minimize delivered
      dose discrepancy from the planned dose.

PMID- 28517266
TI  - SU-E-T-273: Commissioning Motorized Jaws for a Micro-CT/RT.
AB  - PURPOSE: To design, construct and commission a set of computer-controlled
      motorized jaws for a micro-CT to perform conformal image-guided small animal
      radiotherapy. METHODS: We report on the design and evaluation of our custom-built
      motorized orthogonal jaws, which allows the delivery of off-axis rectangular
      fields, installed on a GE eXplore CT 120 preclinical imaging system. The jaws in
      the x direction are independently driven, while the y direction jaws are
      symmetric. All motors have backup encoders, verifying their positions.
      Measurements were performed using the large focal spot (1.0 mm) at 140 kVp, 50
      mA, 25 ms pulse duration, with 220 ms between pulses. Additionally, a Monte Carlo
      beam model of the micro-CT and jaws has been created in BEAMnrc. Square beam
      profiles (2 * 2, 5 * 5, 10 * 10, 20 * 20 and 30 * 30 mm) were measured using EBT2
      film in the center of a 40 * 40 * 40 mm solid water block. A calibrated Farmer
      ion chamber in a 50 * 20 * 70 mm solid water block was used to measure the output
      of three field sizes: 50 * 50, 40 * 40 and 30 * 30 mm. Both setups were simulated
      in DOSXYZnrc. Films were scanned on a flatbed scanner (Epson 1000XL) and
      converted to dose using a fitted calibration curve. RESULTS: Relative output
      factors measured with the ion chamber agree with Monte Carlo simulations within
      2%. Penumbra widths from film agree well with simulations. The averaged random
      error of positioning both jaws is estimated at less than 0.1 mm. Finer
      calibration points will improve the absolute jaw positioning errors. CONCLUSION:
      The computer-controlled motorized jaws can be positioned reliably down to sub
      millimeter resolutions. Upon completion of small field dosimetry (< 1 cm), this
      will be ready for conformal radiotherapy for small animals.

PMID- 28517265
TI  - SU-E-T-317: Dynamic Modulated Brachytherapy (DMBT): Robotic Applicator Design.
AB  - PURPOSE: To investigate the hardware necessary for implementing our Dynamic
      Modulated Brachytherapy (DMBT) treatment concept for rectal cancer. METHODS: The
      DMBT robot has three major parts: 1) shield and shield delivery module, 2)
      controlling module, and 3) DMBT controlling and monitoring software. The shield
      is a tungsten alloy cylinder (r=0.95cm, l=4.5cm) with a 5.5mm rectangular-shaped
      opening. The shield is controlled by an aluminum pipe with gear set (1:3) and
      linear actuator (2mm/turn). An Ir-192 radiation source will be placed through the
      aluminum pipe. The power source is a Nema-17 stepping motor with EvoDrive ST-17
      (EVA Robotics, Queensland, Australia) and USB-6009 DAQ (National Instrument,
      Austin, TX). With our in-house operating program through LabView (National
      Instrument, Austin, TX), we can make and load plans for treatment as well as
      testing. Checking the shield position is also possible through the operating
      program. For safety, a lexan sheath tube and emergency buttons are built-in.
      RESULTS: The DMBT robot has 2 degrees of freedom, which are linear translation
      and rotation. With our power delivery system, the spatial resolutions are
      0.0125mm (linear stage) and 0.012Es (rotation). In 0.5s, motors achieve the
      desired position with the maximum speeds 450 step/s (1Es), 7,500 step/s (30Es),
      and 12,000 step/s (5mm). Four registers are triggered with USB-6009 DAQ signals.
      The operating program includes gages for checking shield position, loading
      treatment plans, and safety buttons. CONCLUSIONS: In all, we have designed the
      hardware components of the DMBT system for rectal cancer. For treatment, the
      system needs more elements to support the DMBT robot; lexan sheath tube holder,
      DMBT robot security joint, and a system for reducing friction between the tube
      and shield. We will also refine our system to be more compact by using DC
      servomotors instead of the larger Nema-17 stepping motors.

PMID- 28517267
TI  - SU-E-T-284: Surface Dose Evaluation for Beams with and without Flattening Filter
      in Breast Cancer Treatment.
AB  - PURPOSE: To evaluate surface doses for beams with and without flattening filter
      (FF and FFF) in breast cancer treatment plans. Measurements were performed for
      validation. Delivery:TrueBeam, used in this study, is a linear accelerator newly
      designed to deliver both flattened and flattening filter free beams. Planning:
      Eclipse treatment planning system (TPS) is commissioned and utilized. We used 6
      MV half beams from FFF mode to plan standard tangential breast treatments due to
      its similar shape to wedged FF beams. We compare these plans with those from 6MV
      flattened beams with 30 degrees  wedges. Measurement Validation: We used a Rando
      phantom and InLightTM nanoDots Optically stimulated luminescence dosimetry(OSLD)
      system to measure surface doses from FFF beams. Medial, apex and lateral
      locations from central plane, as well as positions from caudal and cranial
      regions, were included. RESULTS: Planning comparison: surface doses from plans
      with FFF beams were2.2%-4.7% lower than those with flattened beams with wedges,
      when doses at deeper depth from central axis stay close in value. Measurement
      validation: In the apex region of central plane,the OSLD readouts are 4.5% - 6.3%
      higher than calculated. In the caudal, cranial and medial regions, TPS
      underestimated the surface dose from 7.2-8.7%. CONCLUSIONS: For standard
      tangential breast plans, surface doses are lower with FFF beam than with
      flattened beams with wedges. The surface doses from FFF beams were validated with
      OSLD measurements, taking into account the uncertainty of the dosimeter and its
      angular dependence.

PMID- 28517268
TI  - SU-E-T-306: An Optimized Dosimetry Study Comparing a Multichannel Cylinder versus
      Single Channel Cylinder in the Treatment of the Vaginal Cuff or Vagina with High
      Dose Rate Brachytherapy.
AB  - PURPOSE: Elekta/Nucletron introduced a new CT/MRI multi-lumen brachytherapy
      applicator to optimize dosimetry and treatment of vaginal targets. The design
      includes several peripheral channels isotropically placed 5mm inside cylinder
      surface with a separate central channel allowing single lumen brachytherapy as an
      option. We compared optimized dosimetry plans between single channel versus multi
      channel to determine potential dosimetric advantages in vaginal cancer treatment
      after hysterectomy. METHODS: Patients were planned by CT simulation with each
      fraction of vaginal brachytherapy for postoperative endometrial cancer or vaginal
      cancer. Twenty CT cases representing five patients were compared. A single
      channel (standard) treatment approach was planned to the prescribed depth with
      the goal of providing maximal coverage to the tumor bed (the 5mm rind typically).
      Doses to the bladder and rectum were recorded by dose volume histogram. A second
      treatment plan was generated using a multichannel approach. The Oncentra
      brachytherapy planning system was used to generate both forward and IPSA inverse
      treatment plans. The target coverage percentage and doses to the bladder and
      rectum were optimized. RESULTS: The comparison demonstrates an improved V90, V95,
      V100 of the prescribed dose to the 5mm vaginal cuff rind was achieved in all
      cases. The average improvement in coverage was 9% (between 6-13%) for the cases
      evaluated. The multi-channel plan also reduced the maximal dose (hot spot) to the
      bladder and rectum within a range of 9-16% and 5-15% respectively. An increased
      non-critical vaginal mucosal dose of up to 75% was delivered as a result of the
      reduced bladder and rectal exposure via multichannel procedure. CONCLUSIONS:
      Optimization of vaginal cuff brachytherapy is possible by using a new multi-lumen
      vaginal cylinder. The new device can increase the therapeutic ratio by improving
      target coverage with a reduction in the potential toxicity of hot spots to the
      adjacent organs.

PMID- 28517269
TI  - SU-E-T-321: Dynamic Modulated Brachytherapy.
AB  - PURPOSE: We introduced the concept of Dynamic Modulated Brachytherapy (DMBT) for
      rectal cancer, last year. To continue our work, we studied different shield
      designs and investigated the system's tolerance against systematic setup errors.
      METHODS: As previously presented, our system uses a cylindrical tungsten shield
      to create a directional radiation profile, which is modulated through translation
      and rotation using a specialized robotic arm. We used Monte Carlo simulations and
      an in-house gradient projection optimization algorithm to look at key design
      parameters. First, we used ideal phantoms to study treatment quality from shield
      radii ranging 0.5-1.5 cm in 0.25 cm increments. Second, using 36 patient plans,
      the dependence on radial source position within the shield was studied. We also
      analyzed the tolerance of the system to systematic setup errors by simulating
      dose distributions from possible inaccuracies. These included translational and
      rotational errors as well as possible Ir-192 source misplacements by the
      afterloading system. RESULTS: Changes in shield radius followed steady patterns.
      Increasing the radius showed a consistent increase in dose conformality to the
      tumor volume and better sparing to surrounding tissues. However, there was also a
      linear increase in total dwell time. There was a trade off to changing the radial
      position of the source. As the source is brought away from the center, there is a
      decrease in conformality to the tumor volume, but sparing to healthy tissues was
      increased and there is a decrease in total dwell time. We found that any
      potential setup errors for our system, within anticipated margins, had negligible
      effects on the dose distributions (< 3% deviation). CONCLUSION: Various
      parameters for shield designs must be balanced for an effective DMBT application.
      It was found that the system is highly robust against systematic setup
      uncertainties.

PMID- 28517271
TI  - SU-E-T-277: Hypothesis and Design of an Integrated X-Ray/Bioluminescent Imaging
      (BLI) and Tomography (BLT) System for the Study of Radiation and Treatment in
      Small Animals.
AB  - PURPOSE: Design and construct an integrated x-ray/bioluminescent tomography (BLT)
      system (with BLT being our initial focus) that can function as a standalone
      research apparatus and also on-board the SARRP to guide focal irradiation. In
      addition, it is aimed to enhance the BLT of the system to improve target
      localization by incorporating multi-projection, multi-spectral BL images, as well
      as CT 'priors'. METHODS: The SARRP system integrates a portable robotic
      translational/rotational stages system and an x-ray source which in the new
      system development the x-ray source is replaced with the PXS10-65 W model rated
      at maximum 130 kV having a variable small focal. A high performance, low noise,
      CCD camera mounted on a light-tight housing along is used for the aim of the BL
      imaging and tomography. In the new setup of the BLI system, the camera-filter
      mirror assembly is attached to a motorized gantry to acquire images in angles
      between to while the position of the camera does not block the path of the x- ray
      beam. Innovatively, a 3-mirror arrangement is implemented to eliminate the need
      to rotate the CCD camera for capturing images. Furthermore, the robotic stage can
      be vertically adjusted to allow BLI imaging of multiple animals. RESULTS: To
      validate the accuracy with the on-board x-ray and BL tomography can be used to
      localize a BL tumor target and the minimum beam expansion to ensure radiation
      coverage of the target. The validation will employ phantoms and
      immunohistochemistry analysis of radiation damage in irradiated BL tumor models
      in vivo. The proposed system is currently under development and envisioned to be
      calibrated and evaluated along with the stand-alone radiation system.
      CONCLUSIONS: The novelty of embedded BLI guidance system is to enable the
      unprecedented focal irradiation of the small volumes of tumors which are more
      realistic in human disease.

PMID- 28517270
TI  - SU-E-T-267: Construction and Evaluation of a Neutron Wall to Shield a 15 MV Linac
      in a Low-Energy Vault.
AB  - PURPOSE: To design and quantify the shielding efficacy of an inner Borated
      Polyethylene (BPE)wall for a 15 MV linac in a low energy vault. METHODS: A Varian
      TrueBeam linac with a maximum photon energy of 15 MV was installed in asmaller,
      preexisting vault. This vault originally housed a low-energy machine and did not
      havesufficient maze length recommended for neutron attenuation. Effective dose
      rate calculationswere performed using the Modified Kersey's Method as detailed in
      NCRP Report No. 151 andfound to be unacceptably high. An initial survey following
      the machine installation confirmedthese calculations. Rather than restrict the
      linac beam energy to 10 MV, BPE was investigatedas a neutron moderating addition.
      An inner wall and door were planned and constructed using4'*8'*1" thick 5% BPE
      sheets. The resulting door and wall had 2" of BPE; conduits and ductwork were
      also redesigned and shielded. A survey was conducted following construction of
      thewall. RESULTS: The vault modification reduced the expected effective dose at
      the vault door from 36.23to 0.010 mSv/week. CONCLUSION: As specific guidelines
      for vault modification are lacking, this project quantitativelydemonstrates the
      potential use of BPE for vault modification. Such modifications may provide alow
      cost shielding solution to allow for the use of high energy modes in smaller
      treatment vaults.

PMID- 28517272
TI  - SU-E-T-299: Proton Pencil Beam Spot Scanning Phase Space in the IBA System and
      the Clinical Implications for Superficial Targets.
AB  - PURPOSE: In the treatment of superficial lesions with proton Pencil Beam Scanning
      (PBS), spot size is dominated by the nozzle contribution. Accuracy of phase-space
      modeling is therefore paramount. IBA's Dedicated (DN) and Universal Nozzles (UN)
      have different designs and, consequently, characteristics. Here we report the
      phase spaces of these two nozzles, without and with a range shifter (RS).
      METHODS: In-air spot fluence measurements were made for five proton energies:
      225, 210, 180, 150 and 115 MeV and at five distances from isocenter pertinent to
      SAD-type treatments: +33, +20, +10, 0 and -10 cm ('+' implies upstream), without
      and with a 7.5 cm water-equivalently-thick RS (sufficient to pull back the lowest
      energy Bragg peak to patient surface), fixed with its upstream side 41 cm from
      isocenter. Data collected on a fixed horizontal beam-line with a DN and a gantry
      mounted UN were compared. The full-width-at-half-maximum (FWHM) of a Gaussian fit
      to each spot fluence profile was extracted along the two principal axes. RESULTS:
      With no RS, the proton spots are ~20-70% larger at isocenter in the UN than in
      the DN. Spots are less asymmetric, and eccentricity increases more slowly with
      energy, in the UN than in the DN. Over the 33 cm in-air travel upstream of
      isocenter, the spot FWHM varies by less than ~2 mm. However, spot asymmetry
      becomes more severe upstream (for 115 MeV spots, 30-40% compared to <20% at
      isocenter for DN, but similar and <10% for UN). With an RS, spot FWHM at
      isocenter increases by 12.7 mm from 8.3 mm (DN) and 10.7 mm from 13 mm (UN) for
      150 MeV protons (typical for brain treatments). With no RS, relatively distance
      independent spot size facilitates SAD-type treatments. For patients with
      superficial lesions, where an RS is required and the phase space varies rapidly
      with distance, the RS should be permitted at two additional locations. US Army
      Medical Research and Materiel Command under Contact Agreement No. DAMD17-W81XWH
      04-2-0022.

PMID- 28517273
TI  - SU-E-T-288: Skin Dose Measurement of Whole Brain with GAFCHROMIC EBT2 Films.
AB  - PURPOSE: To measure skin dose of whole brain irradiation of a humanoid unsliced
      phantom treated by standard lateral fields with GAFCHROMIC EBT2 films. METHODS:
      The head and neck of the whole body phantom was scanned at the slice thickness of
      2mm. A whole brain plan using 6MV beam was created with standard parallel opposed
      lateral fields. The isocenter was placed at the outer canthus to avoid divergence
      to orbital structures. The plan was normalized to the calculation point and with
      = 95% of brain volume covered by = 95% of prescription dose. The EBT2 films were
      carefully cut and labeled with same orientation in the film calibration and skin
      dose measurement. EBT2 film was calibrated in the reference condition with
      various dose (0-10Gy). After the phantom was positioned for treatment and correct
      setup was verified by kV-kV imaging and CBCT, the films were placed at various
      sites and irradiated. An Epson flatbed color scanner was utilized and the scanner
      response from the red channel of the RGB image was used as the density value for
      the estimation of dose. The comparison was made between the measured dose and the
      planned dose for different head locations. RESULTS: Our preliminary results
      indicated that the measured skin dose agrees with the planned dose within 10% for
      the sites centered in the treatment fields such as mid right/left sphenoid bones.
      For the sites outside or near the edge of the treatment fields, such as the
      right/left orbits and low chin, the measured dose is significantly different from
      the planned dose (>15%). CONCLUSIONS: Skin dose of whole brain irradiation could
      be measured by GAFCHROMIC EBT2 films. The difference between the measured dose
      and the planned dose varies significantly depending on the location of interest
      relative to the treatment field. Further investigation is needed.

PMID- 28517274
TI  - SU-E-T-310: Micro-Dosimetry Study of the Radiation Dose Enhancement at the Gold
      Tissue Interface for Nanoparticle-Aided Radiation Therapy.
AB  - PURPOSE: Gold nanoparticles (AuNP) have been proposed to be utilized for local
      dose enhancement in radiation therapy. Due to a very sharp spatial fall-off of
      the effect, the dosimetry associated with such an approach is difficult to
      implement in a direct measurement. This study is aimed at establishing a micro
      dosimetry technique for experimental verification of dose enhancement in the
      vicinity of gold-tissue interface. METHODS: The spatial distribution of the dose
      enhancement near the gold-tissue interface is modeled with Monte Carlo (MC)
      package MCNP5 in a 1-dimentional approach of a thin gold slab placed in an ICRU-4
      component tissue phantom. The model is replicating the experiment, where the dose
      enhancement due to gold foils having thicknesses of 1, 10, and 100MUm and areas
      of 12.5*25mm2 are placed at a short distance from clinical HDR brachytherapy (Ir
      192) source. The measurements are carried out with a thin-film CdTe-based
      photodetector, having thickness <10MUm, allowing for high spatial resolution at
      progressively increasing distances from the foil. RESULTS: Our MC simulation
      results indicate that for Ir-192 energy spectrum the dose enhancement region
      extends over ~1 mm distance from the foil, changing from several hundred at the
      interface to just a few percent. The trend in the measured dose enhancement
      closely follows the results obtained from MC simulations. CONCLUSIONS: AuNP's
      have been established as promising candidates for dose enhancement in
      nanoparticle-aided radiation therapy, particularly, in the energy range relevant
      to brachytherapy applications. Most researchers study the dose enhancement with
      MC simulations, or experimental approaches involving biological systems, where
      achievable dose enhancements are difficult to quantify. Successful development of
      micro-dosimetry approaches will pave a way for direct assessment of the dose in
      experiments on biological models, shedding some light on apparent discrepancy
      between physical dose enhancement and biological effect established in studies of
      AuNP-aided radiation therapy. No conflict of interest.

PMID- 28517275
TI  - SU-E-T-271: Irradiating a Single Hippocampus in a Small Rodent Using VMAT-
      RapidArc SRS: Preliminary Data.
AB  - PURPOSE: To develop and optimize the procedures for the precise irradiation of
      the hippocampal region in a rodent with minimum radiation dose to the remainder
      of the brain. For this purpose, VMAT-RapidArc SRS was used to irradiate one
      hippocampus of athymic nude (ATN) rats. Prescribed dose was verified through TLD
      measurements and spared brain region(s) were confirmed through
      immunohistochemical analysis postmortem. METHODS: Seven ATN rats, 10-12 weeks old
      underwent human-like radiation treatment planning followed by SRS. MRI and CT
      axial images of 0.8 mm thickness of the rat's skull were acquired and transferred
      to ECLIPSE treatment planning software where brain, right and left hippocampi
      were contoured. A VMAT-RapidArc plan consisting of two 3600 axial arcs and two
      1200 vertex arcs irradiated the left hippocampus only to a dose of 10 Gy.
      Treatment was delivered using a 6 MV photon beam from a Trilogy Linac equipped
      with OBI. TLD measurements were performed prior to treatment using a custom made
      phantom that simulated the rat's brain and body. Orthogonal x-ray images taken
      with the OBI and co-registered to DRR images were used to adjust the rat's
      treatment position. One month post- irradiation, rats were sacrificed and brain
      dissection was performed to verify the radiation effects in the targeted and non
      targeted regions. RESULTS: Percent differences between calculated and measured
      dose were ~12% which was expected due to the small field sizes (<2cm) used.
      Immunohistochemistry analysis revealed a significant reduction in cell population
      in the ipsilateral hippocampus while cell populations comparable to those in a
      non-irradiated subject were observed in the contralateral hippocampal region.
      CONCLUSIONS: Present results demonstrate that precise irradiation of small
      volumes within a rat's brain can be achieved with human-like image-guided VMAT
      RapidArc treatment. Postmortem analysis of the rat brain provides evidence of
      high-precision targeted radiation damage and dose sparing.

PMID- 28517276
TI  - SU-E-T-297: Proton-Therapy System for Treatment of Macular Degeneration and
      Ocular Malignancies.
AB  - PURPOSE: To commission a proton-therapy system for the treatment of uveal
      melanoma and age-related macular degeneration. METHODS: Proton therapy system is
      the proto-type of a commercial product developed by Ion Beam Applications. Proton
      beam is brought into the treatment room at 105 MeV through a fixed beam line. A
      single-scattering system with absorber/scattering foils spreads the beam into a
      Gaussian profile. A library of 10 range-modulator wheels and 16 range-modulator
      blocks generate spread-out Bragg peaks of various range and modulation width.
      Source-to-axis distance of the system is 169 cm. Two orthogonal digital x-ray
      panels are used for alignment. EyePlan software is used both for both treatment
      planning and in-room alignment. RESULTS: Range can be varied continuously between
      0.5 and 3.4 g/cm2 . Range accuracy is measured to be better than 0.05 g/cm2 .
      Modulation width can be varied in steps of =0.3 g/cm2 with an accuracy of 0.05
      g/cm2 or 2%. Maximum aperture diameter is 2.5 cm and maximum dose rate >32
      Gy/min. Strong dependence of output on range (7%/mm) and dose rate
      (0.2%/(Gy/min)) is found. Distal and lateral fall-off (80%-20%) are =0.23 and
      =0.18 g/cm2 and do not depend much on range or depth. When reducing the aperture
      diameter to 6 mm no significant change is observed in shape of depth-dose curve
      or absolute dose (<2.5%). Measurements show a significant portion of the dose at
      shallow depth (=0.7 g/cm2 ) is delivered by protons scattering off of snout
      elements. Simple collimation could reduce this effect. CONCLUSION: The dosimetric
      and positioning properties of the IBA ocular proton system are adequate to treat
      ocular lesions with acceptable clinical margins. Suggested improvements include
      limiting the output-dependence on range and reducing snout scatter.

PMID- 28517277
TI  - SU-E-T-281: Secondary Light-Ions in Carbon-Ion Therapy: A GEANT4 Simulation of
      LET and Dose Contributions.
AB  - PURPOSE: The purpose of this investigation was to reveal the dosimetric
      characteristics and contributions of the secondary light ions produced from
      carbon-ion beams in water via a GEANT4 simulation. METHODS: GEANT4 low energy
      electromagnetic physics processes were used for all ions. The hadronic
      interactions of protons and neutrons are simulated using low energy elastic
      interactions while inelastic scattering is simulated with a binary cascade (BIC)
      model. Other inelastic light-ion interactions are being simulated through the
      application of a quasi-molecular dynamics (QMD) model. A 27 liter cubic water
      phantom consisting of 3000 packed rectangular detector sheets (30 cm * 30 cm *
      0.1mm) was used in this simulation. A 1 mm diameter pencil beam of 1 million
      incident carbon-ions was used in all simulations presented. The incident energies
      per nucleon of the carbon beams studied were selected 155 MeV, 262 MeV and 369
      MeV. The energy deposition, total kinetic energy, fluence, and dose averaged LET
      of each secondary particle produced within each detection sheet was determined to
      study their variations with depth. The particles investigated were gamma,
      neutron, electron, positron, proton, deuteron, triton, alpha, He- 3, Li-6, Li-7,
      Be-7, Be-9, Be-10, B-10, B-1 1, C-1 1, C-12, C-13, C-14, N-13, N-14, N-15, O-16.
      RESULTS: The relative dose contributions of four secondary ions (B-11, C-1 1,
      Alpha and Proton) were found to be each greater than 1%. The highest dose
      averaged LET value was from N-13, though its averaged dose contribution was less
      than 5*10-4 %. CONCLUSIONS: The secondary particles contribute small portion to
      the total dose deposited from primary carbon beam. Though heavier ions (N, O)
      show significant higher LET values, their relative dose contributions were
      negligible.

PMID- 28517278
TI  - SU-E-T-303: Practical Considerations for Maximizing Heat Production in Novel
      Thermo-Brachytherapy Seed Prototype.
AB  - PURPOSE: Our recently proposed thermo-brachytherapy seed offers a convenient
      approach to radiation sensitization with heat in treatment of solid tumors
      through concurrent administration of hyperthermia and brachytherapy. The seed
      consists of a titanium capsule, containing radioactive I-125 and a ferromagnetic
      core, serving as a source of self-regulating hyperthermia when placed in an
      alternating electromagnetic field. We present an experimental study of the
      magnetic properties of ferromagnetic Ni-Cu alloy, and develop a protocol for
      obtaining the material capable of the maximum heat generation. Based on the
      practically achievable temperature interval we evaluate the effect of thermal
      expansion on the seed components during the hyperthermia treatment. METHODS:
      Alloy samples of Ni1-xCux (0.28= * =0.3) were prepared by arc melting method in
      argon atmosphere. The ingots were annealed in vacuum at 1000 degrees C for 12
      hours. These samples were cut into pieces and used for magnetization measurements
      with SQUID magnetometer. The thermal expansion along greatest dimension of each
      component of the purposed seed was estimatedfor temperature increase from 37 to
      60 EsC. RESULTS: The annealed samples show sharp Curie transition at temperature
      TC~50 degrees C, varying with the alloy concentration. However, the un-annealed
      sample does not show the clear transition, thus indicating a strong influence of
      thermal treatments on the magnetic properties of the Ni-Cu alloy. The annealing
      favors atomic diffusion, and leads a sample homogenization, minimizing
      composition fluctuations and maximizing the heat generation. The effect of the
      temperature rise on the thermal expansion of each component of the seed was found
      to be negligible. CONCLUSIONS: We have established the thermal annealing protocol
      resulting in the maximum heat generation from the Ni- Cu alloy core. The
      negligible change in dimensions of the seed components due to heating assures the
      safety of the implementation of thermo-brachytherapy seed for hyperthermia
      treatments. This project is supported through NIH grant # 1 R41 CA153681-01A1.

PMID- 28517279
TI  - SU-E-T-316: New Design of the Valencia Applicators to Reduce Radiation Leakage.
AB  - PURPOSE: The Valencia applicators are designed to treat skin lesions with the
      microSelectron-HDR afterloader. Although the radiation is highly directed to the
      treatment area, radiation might leak through the backside of the applicator.
      Recently, the manufacturer has introduced a new applicator design to reduce such
      radiation leakage. This new design consists mainly in the addition of about 4 mm
      of tungsten in the backside of the applicator making it thicker. The purpose of
      this study is to evaluate by means of the Monte Carlo method the radiation
      leakage of this new design and to evaluate whether this modification affects the
      dose rate distributions in the treatment area. METHODS: The complete geometry of
      the new applicators has been introduced in the Monte Carlo code GEANT4. The
      applicators have been located on the surface of a cylindrical water phantom
      following a methodology similar to the used in the original study of the Valencia
      applicators by Granero et al [Med.Phys 2008;35:495-503]. Kerma in the water
      phantom and kerma in air outside the phantom have been evaluated to estimate the
      radiation leakage of the new designed Valencia applicators. RESULTS: The Monte
      Carlo simulations of the new applicators show that the radiation leakage has been
      reduced significantly from the previous design. The largest radiation leakage of
      this design is now about 30% of the dose at the prescription point and about 10%
      at 1 cm from the backside of the applicators. The dose rate distributions in the
      area of treatment have not changed. CONCLUSIONS: In this study the radiation
      leakage of the new design of the Valencia applicators has been obtained. The
      radiation leakages have been largely reduced from the previous design without
      compromising dose rate distributions in the treatment area.

PMID- 28517280
TI  - SU-E-T-283: Carbon Ion Therapy Innovations in Dosimetry and Dose Delivery.
AB  - OBJECTIVE: Carbon ion particle therapy delivers sharp Bragg's peaks, and hence
      can produce dose delivery of very high precision and conformality. To complement
      this characteristic, particle therapy centers implement a number of technologies
      unique to these centers, and are not commonly known to the medical physics
      community. This work outlines these adopted technologies. METHODS: Particle
      therapy centers develop technologies to meet the needs of patient safety, dose
      delivery accuracy, and imaging requirements complementing these state-of-the-art
      centers. Through the use of literature reviews and publicly available documents,
      we produced a compilation of some of these innovations, a number of them unique
      to the centers themselves. RESULTS: The centers based in Bloomington, USA, Chiba,
      Japan, Harima Japan, Gunma, Japan, Heidelberg, Germany, and Pavia, Italy were
      reviewed. Interestingly, 60% of centers reviewed developed in-house innovations
      to address the needs of particle therapy, and all but one had at least one
      technology unique to its center. For example, Bloomington's MPRI developed a 3D
      dosimeter used in particle beam measurement. The patient couch systems
      implemented in Chiba, Japan and now Gunma, Japan are unique to the centers.
      Heidelberg's HIT developed the world's first carbon ion gantry. Italy's CNAO has
      a unique patient positioning system. CONCLUSIONS: Particle therapy centers,
      despite being at the forefront of technology in delivering radiation to patients,
      have not widely disclosed treatment delivery strategies and dosimetry techniques,
      despite the material being potentially useful to the radiotherapy community. This
      work is an effort in comparing and contrasting these innovations.

PMID- 28517281
TI  - SU-E-T-305: Limitations of Using DICOM Data for BrachyVision Treatment Plan
      Evaluation.
AB  - PURPOSE: To evaluate the accuracy of a real-time automated method of performing
      dosimetric quality assurance using Eclipse DICOM files for patients receiving HDR
      brachytherapy and IMRT. METHODS: GYN patients are treated with concurrent high
      dose rate brachtherapy and IMRT. The dosimetric parameters were obtained through
      an in-house QA program developed using Matlab. The DICOM files containing DVH
      data for organsat-risk (OAR) were analyzed Dosimetric data for 7 patients (total
      42 fractions) were collected for bladder, rectum and sigmoid. The accuracy of the
      dosimetric parameters was estimated by comparing the parameters obtained from the
      DICOM based QA program and those in BrachyVision. RESULTS: The maximal dose
      values (Dmax) for the OARs obtained using the DICOM-based program are
      significantly smaller than those valued reported in BrachyVision by 36.2%-48.3%.
      The mean dose has a deviation from 1% - 2.4%. The dose for the volume of 2cc
      (D2cc) has a difference up to 7.6% for structures with the volume larger than 200
      cc. The average difference of D2cc is 0.5% for structures less than 200 cc. We
      found that Eclipse BrachyVision only exports DVH data down to a volume equivalent
      to 1% of the maximum volume for a given structure. Therefore, the reported
      maximal dose values obtained from DICOM RT dose file do not accurately reflect
      the maximum dose in a treatment plan. This will also slightly affect the mean
      dose calculation and D2cc when the structure volume is larger than 200cc.
      CONCLUSIONS: The automatic QA tool based on DICOM files provides a quick
      retrieval of dose to organs-at-risk and coverage of targets. However, maximal
      dose to structures is not accurate due to the truncationof the DVH information
      contained in DICOM files.

PMID- 28517282
TI  - SU-E-T-320: A New Verification Phantom for GYN Brachytherapy Applicators Using
      GafChromic - Films.
AB  - PURPOSE: Brachytherapy plays an important role in radiation therapy a wide range
      of tumor sits such as vaginal, cervical and endometrial cancers. The purpose of
      this project was to design, fabricate and verify a new phantom for dosimetric
      verification at small distances from GYN applicators used with GZP6 cobalt-60 HDR
      system. METHODS: A new phantom has been designed and fabricated from 90 slabs of
      18*16*0.2 cm3 Perspex to accommodate one tandem and two ovoids. The thin layer of
      the slabs was chosen to place GafChromic films in between the slabs for dosimetry
      with GZP6 cobalt-60 HDR system. For verification of this device, an assembly
      composed of a large ovoid size (3cm diameter) and tandem #1 with the least
      curvature was selected in this study. With this assembly, GafChromic films were
      exposed using a plan with 500 cGy dose delivery to point "A". The irradiated
      films were scanned. The responses of the films were converted to dose by
      calibrating samples of these films using a cobalt-60 teletherapy system in the
      range of 25 to 800 cGy dose. The measured isodose curves with the films were
      compared to calculated isodose lines by the treatment planning software. RESULTS:
      The Result of these investigations indicated differences of up to +/- 23 %
      between the planning and measured dosimetry at different points in GYN implant
      with cobalt-60 HDR source of GZP6 system. Therefore, this phantom enabled us to
      confirm the accuracy of radiation delivery to the GYN patients with cobalt-60 HDR
      source of GZP6 system. CONCLUSIONS: The new phantom design could be utilized for
      the QA procedure of the GZP6 cobalt-60 HDR system as well as the Ir-192 HDR
      system to confirmation the accuracy of dose distribution in GYN implants,
      especially in non-traditional implants. The Radiotherapy Department of Shahid
      Beheshti University at Shohada hospital sponsored the purchase of the phantom
      materials and films used in the investigations.

PMID- 28517283
TI  - SU-E-T-266: Shielding Measurements for a Proton Therapy Facility.
AB  - PURPOSE: This paper is a follow up on the analytical calculations for the Roberts
      Proton Therapy Center with empirical data to determine the precision of the
      calculations from Avery, et al. METHODS: Neutrak dosimeters were placed in two
      sets around the facility while it was in operation at points of interest examined
      in Avery, et al. The doses to these dosimeters were recorded over one month for
      one set and two months for the other. Dosimeters that both recorded a dose and
      could be practically examined were compared to the doses predicted via the
      analytical method of Avery, et al. at their point of placement. RESULTS: Two
      points showed a less than 10% difference to the calculated doses. One point
      shielded by both concrete and pre-cast blocks and one point shielded by both
      concrete and the facility's cyclotron were not as precise. CONCLUSIONS: The
      analytical calculation method explored in Avery, et al. is fairly precise in
      describing the dose at various points in the facility shielded only by concrete.
      for materials other than concrete, such as the make-up of the cyclotron or
      varying wall material, it warrants follow up calculations using the same method.

PMID- 28517284
TI  - SU-E-T-296: Optimization of the Energy Selection System with Varying Magnetic
      Field for Laser-Accelerated Proton Beams.
AB  - PURPOSE: Laser-based accelerated proton beams are unsuitable for clinical use
      because of their broad energy spectra. For this reason, it is essential to employ
      an energy selection system (ESS). The purpose of this study is to determine
      optimum parameters of the ESS which uses a varying magnetic field to generate
      Bragg-peak. METHODS: We simulated an accelerated proton beams using radiation
      pressure acceleration mechanism with carbon-proton mixture target. The density
      ratio (n = 6) between the protons and the carbon ions is one of optimization
      parameters in determining the accelerating mechanisms. The ESS was implemented by
      the Geant4 Monte Carlo toolkit. In order to optimize the hole size and position
      of the energy selection collimator, and magnetic field at ESS, these parameters
      were simulated for acquiring energy and dose distributions by changing each
      values. RESULTS: The proton energy distributions had a poly-energetic
      distribution after passing through the ESS. As the magnetic field was increased,
      the mean energy of the proton beams also was increased. Also as the hole size was
      increased, the energy bandwidth of proton passed through the ESS was increased.
      The hole size and position of the energy selection collimator were effectively
      optimized to 2 cm and 5 cm from the z-axis, respectively. CONCLUSIONS: We
      simulated laser-accelerated proton beams using ESS for generation of Bragg-peak.
      Our results suggest that the ESS with magnetic field variation can effectively
      generate a Bragg-peak suitable for use in proton radiation therapy. Our ESS can
      be applied to pencil beam scanning proton therapy.

PMID- 28517286
TI  - SU-E-T-287: Patterns of Patient Specific Dosimetry in Total Body Irradiation.
AB  - PURPOSE: Total body irradiation (TBI) is commonly used for conditioning prior to
      transplant in hematologic and immunologic diseases. Due to variability in body
      thickness, achieving dose uniformity across body within +/-10% of the prescribed
      dose is challenging. The dose uniformity is further complicated by, techniques
      and beam energy used, lung shielding and selection of detector. The translational
      table technique for TBI could compensate for estimated delivered dose to whole
      body by adjusting couch speed during treatment. However, it is difficult to
      accurately estimate the dose by calculation and hence in vivo dosimetry (IVD) is
      routinely performed for TBI. The patterns of patient specific dosimetry, IVD are
      presented in this study. METHODS: Under IRB exempt status, 161 patients who
      received TBI treatment between 2006 and 2011 were retrospectively analyzed using
      the treatment records from Cobalt-60 teletherapy unit and translational treatment
      couch. During treatment, IVD detectors (TLD, diode, or MOSFET) were placed on
      patient surface; both entrance and exit dose were recorded at the patient's head,
      neck, mediastinum, umbilicus, and knee. When large differences between prescribed
      and measured dose were observed, the dose delivery was corrected for subsequent
      fractions by adjustment in couch speed and/or bolus placement. RESULTS: Across
      the entire cohort, the mean (range) percent variance between calculated and
      measured dose were -2.3% (-66.2 - 35.3), 1.1% (-62.2 - 40.3), -1.9% (-66.4 -
      46.6), -1.1% (-35.2 - 42.9), and 3.4% (-47.9 - 108.5) for head, neck,
      mediastinum, umbilicus, and knee, respectively. When the dose differences for
      multiple fractions were averaged, the compliance (+/-10%) between prescription
      and measured dose was improved as at umbilicus from 83.9% to 98.5%. CONCLUSIONS:
      Actual dose measurement analysis of TBI patients reveals a potentially wide
      variance from calculated dose. Dose uniformity can be significantly improved with
      immediate feedback after the first fraction prior to subsequent treatments. This
      work was supported by the JSPS Core-to-Core Program No. 23003.

PMID- 28517285
TI  - SU-E-T-276: Treatment Planning Strategies for Lung Injury Studies in Rat Models
      in 6 MV Delivery.
AB  - PURPOSE: To study planning strategies that can be used in small animal radiation
      induced lung toxicity experiments using 6 MV accelerator with high density MLC.
      METHODS: Three different types of plans were designed on CT images of a Sprague
      Dawley rat model to irradiate 50% of the total lung volume (lung divided into
      apex and base) with a prescription dose of 24 Gy to the partial lung. Two VMAT
      arc therapy plans were optimized to cover to the prescription dose, either the
      apex or base of the lung. Two AP- PA plans were designed to completely block
      either lung apex or base while irradiating the remaining 50% of the lung.
      Finally, two AP-PA plans were designed to cover, to the prescription dose, the
      apex or base of the lung. The plans were designed and optimized using the Eclipse
      AAA algorithm and recalculated using the MMCTP/EGS/Beam Monte Carlo system.
      RESULTS: When completely blocking the lung base, the apex will be underdosed by
      up to 30%; when completely covering the apex by the prescribed dose, the base
      will receive overdosing (V50%=73%). The VMAT plan leads to a more conformal dose
      distribution and spares unnecessary skin exposure when compared to AP-PA MV or kV
      delivery. Despite the small size of rat model, the 6 MV VMAT delivery is superior
      in terms of dose conformality and sparing of the heart and the non-irradiated 50%
      of the lung compared to the standard, simpler, AP-PA delivery. MC dosimetry in
      lung shows that the delivered dose is 10% higher than predicted by AAA because of
      the predominance of small fields in the delivery. CONCLUSIONS: Clinical state-of-
      the-art planning and delivery techniques can be scaled down accurately to rats.
      The use of these techniques is essential in small animal studies to render
      conclusions of radiation response investigations translatable to human studies.

PMID- 28517287
TI  - SU-E-T-309: Dosimetric Study and Clinical Implementation of an HDR Applicator of
      SAVI for Partial Breast Irradiation.
AB  - PURPOSE: To present clinical implementation and quality assurance for a new HDR
      applicator of Strut-Adjusted Volume Implant (SAVI) for partial breast irradiation
      and the higher-order DVH examined. METHODS: The SAVI applicator with multi
      peripheral struts can be differentially loaded with the HDR source for a
      conformal dose distribution to the lumpectomy cavity. The treatment plan is
      evaluated by a dose volume histogram (DVH) as follows: V90 > 90%, V150 < 50 cc,
      and V200 < 20 cc. A higher-order DVH which may reflect radiation-induced
      toxicity, such as V300, was studied. The SAVI device status was verified by the
      3D CT images and image fusion. Tissue invagination was investigated using an ion
      chamber and film with the cavity filled with air and water merged into a water
      phantom. RESULTS: Twenty-nine patients to date at Mercy Medical Center,
      Baltimore, Maryland were treated with SAVI device. The dosimetric data
      demonstrated the achievements of greater than 90% coverage for V90 at 96.8% and
      94.1% for V95 while keeping a low V150 at 33.9 cc and V200 at 16.5 cc. V300 was
      found to be 2.7 cc in average. Potential uncertainties introduced by the SAVI
      applicator motion were a 3% variation in dose caused either by a 3-mm}
      translation or a rotation of 3 degree. CONCLUSIONS: Multiple catheters of the
      SAVI applicator allows for optimal and conformal dose distribution around a
      lumpectomy cavity while minimizing the dose to adjacent normal structures such as
      skin and ribcage. Multiple imaging techniques are capable to verify cavity
      variation, strut collapse or relative motion, and device shift. A nearly fully
      loaded dwell source position produced the discrepancy of less than 3% and allow
      for optimal and conformal dose distribution to a lumpectomy cavity. Advantages of
      the SAVI applicator have been shown in treating breast cancer with the shallower,
      elliptical, and asymmetric cavity.

PMID- 28517288
TI  - SU-E-T-270: Optimized Shielding Calculations for Medical Linear Accelerators
      (LINACs).
AB  - PURPOSE: The purpose of radiation shielding is to reduce the effective equivalent
      dose from a medical linear accelerator (LINAC) to a point outside the room to a
      level determined by individual state/international regulations. The study was
      performed to design LINAC's room for newly planned radiotherapy centers. METHODS:
      Optimized shielding calculations were performed for LINACs having maximum photon
      energy of 20 MV based on NCRP 151. The maximum permissible dose limits were kept
      0.04 mSv/week and 0.002 mSv/week for controlled and uncontrolled areas
      respectively by following ALARA principle. The planned LINAC's room was compared
      to the already constructed (non-optimized) LINAC's room to evaluate the shielding
      costs and the other facilities those are directly related to the room design.
      RESULTS: In the evaluation process it was noted that the non-optimized room size
      (i.e., 610 * 610 cm2 or 20 feet * 20 feet) is not suitable for total body
      irradiation (TBI) although the machine installed inside was having not only the
      facility of TBI but the license was acquired. By keeping this point in view, the
      optimized INAC's room size was kept 762 * 762 cm 2. Although, the area of the
      optimized rooms was greater than the non-planned room (i.e., 762 * 762 cm 2
      instead of 610 * 610 cm 2), the shielding cost for the optimized LINAC's rooms
      was reduced by 15%. When optimized shielding calculations were re-performed for
      non-optimized shielding room (i.e., keeping room size, occupancy factors,
      workload etc. same), it was found that the shielding cost may be lower to 41 %.
      CONCLUSIONS: In conclusion, non- optimized LINAC's room can not only put extra
      financial burden on the hospital but also can cause of some serious issues
      related to providing health care facilities for patients.

PMID- 28517289
TI  - SU-E-T-280: Optimal Angle for a Dual-Field Stanford Technique for TSET.
AB  - PURPOSE: This study examines the optimal angle for a dual-field Stanford
      technique for TSET at extended SSD (SSD= 1, 2, 3, 4, 5 m) to predict a readily
      available optimal angle for any SSD. METHODS: The optimal angle at various SSDs
      is found using detector array. The diode array consists of 9 diodes placed on a
      vertical board with a measured vertical scale with the origin placed at
      isocenter. The lateral distance ranges from -100 to +75 cm. A square 36*36 cm2
      field is used to deliver dose in HDTSe- delivery mode with a dose rate 2500
      MU/min from a Varian Clinic 2300IX linac. Several pairs of gantry angles for the
      dual field are used, with the first gantry being 70 degrees -78 degrees  and the
      second being 110 degrees  -102 degrees . These Result in a dual field of 90
      degrees  +/- theta (theta = 10 degrees  - 20 degrees ) to build a suitable
      flatness profile on the vertical axis for treatment. The best group is chosen to
      determine the optimal angle for each SSD considered. From these optimal angles,
      an algorithm is determined for any extended SSD treatment. RESULTS: It is found
      that the optimal angle for TSET does change as one varies the SSD. These angle
      groups are specific for each SSD giving definite markers for the algorithm. At an
      SSD of 5 m it has been shown that an optimal angle of theta = 106 degrees 
      produces the best flatness on the vertical axis. While at SSD of 4 m, 9 = 18
      degrees  Conclusions: An algorithm can now be applied for any treatment center
      considering a dual- field Stanford technique for TSET simplifying the physics
      commissioning process for the center in consideration.

PMID- 28517290
TI  - SU-E-T-302: A Simulation Study with Geant4 Investigating the Secondary Prompt
      Gamma Emissions from Incident 40 MeV Protons Onto Various Materials.
AB  - PURPOSE: This study aims to investigate the prompt secondary gamma spectrum and
      thedepth-dose distributions of incident 40 MeV protons onto various phantom
      materials.The goal is to find a relationship between the secondary prompt gamma
      emissions andthe range of the incident particles. METHODS: An application was
      constructed using the Geant4 Monte CarloToolkit utilizing various physics
      packages. Several phantom materials were irradiatedwith a pencil beam of 40 MeV
      protons. These materials include PMMA (C5H8O2,density 1.18 g/cm3 ) and the built
      in Geant4 materials bone, soft-tissue, and water. Foreach simulation, the energy
      deposited from the incident proton was recorded every 1 mmincrement of depth in
      the phantom. The resulting prompt secondary gamma emissionswere recorded from 0
      to 10 MeV in energy bins of 10 keV. RESULTS: The secondary prompt gamma spectrum
      has various peaks. The peaks locatedabout 4.4 and 6 MeV correspond to the carbon
      and oxygen de-excitation photons,respectively. Our simulations show greater
      production of the higher-energy gammaparticles closer to the Bragg-Peak. When we
      plot the oxygen peak against the normalizedBragg-Peak we found that in all
      materials the difference between Bragg-Peak and theoxygen de-excitation photon
      peak to be about 2 mm. The oxygen peak could be used inthe clinic for range
      verification of the incident proton beam. CONCLUSIONS: Our Geant4 Monte Carlo
      application was used to investigate the secondaryprompt gamma emissions from
      incident 40 MeV protons. A relationship was betweenthe 6 MeV peak and the
      incident proton Bragg Peak. We believe that prominent peaksaround 4 and 6 MeV can
      be used to locate the range of the incident beam provided adetector system is
      built that can count these high-energy gamma particles.

PMID- 28517291
TI  - SU-E-T-291: Dosimetry of Double Scattered Proton Beam Fields Used for Cranio
      Spinal Irradiation.
AB  - PURPOSE: To investigate the effect of source to surface distance on treatment
      field lateral penumbra width and the consequence of setup error on the dose
      distribution in the junction between two spinal fields of double scattered proton
      beams. METHODS: The CT images of the Spine Phantom from Radiological Physics
      Center was used to design a double scattered proton beam treatment plan using
      Varian Eclipse treatment planning system. PTV included spinal cord, vertebral
      body and part of spinous process. The PTV was divided into superior and inferior
      parts and two posterior fields were used to cover the targets with the prescribed
      dose. 2D dose was measured using IBA MatriXX and EBT2 film at a depth close to
      the center of SOBPs of both the fields located both at the nominal source to axis
      distance (SAD) of 270 cm and at an extended SAD. The field separation was changed
      by +/-1 mm to study the effect of setup error. The measured and TPS calculated
      dose distributions in verification plans in a water phantom were compared.
      RESULTS: The measured 2-D doses agreed very well with planned ones for individual
      fields. 99% of pixels pass 3%/3 mm dose/distance agreement criteria. The CAX dose
      differences are within 2%. The 80% to 20% penumbra widths at nominal SAD are
      7.4/7.7/7.8 mm for planned/MatriXX/EBT2 film respectively, and about 1 mm wider
      for the extended SAD. The measured maximum dose was about 10% higher than that
      from the plan, and decreased/increased about 7% when the fields were separated by
      +/-1 mm. CONCLUSIONS: The penumbra width is modestly affected by the extended SSD
      often used for patient treatment. Dose in the junction of two fields is very
      sensitive to the setup error and the accuracy of the TPS dose calculation in this
      region may be limited.

PMID- 28517293
TI  - SU-E-T-282: Preliminary Simulation Study for 3 Dimensional Dose Delivery in
      Carbon Beam Active Scanning System of KHIMA.
AB  - PURPOSE: KHIMA (Korea Heavy Ion Medical Accelerator) project has a plan to
      develop and construct a research beam line for carbon beam active scanning
      system. The carbon beam line consists with scanning magnet, beam-monitoring
      system, energy modulation system. In this study, the significant components,
      scanning magnets and ridge filter, were designed for the carbon beam active
      scanning beam line. METHODS: The designed scanning magnet and ridge filter were
      used for 3 dimensional active beam dose delivery simulation by Geant4 Monte Carlo
      code. The target volume of the active scanning was 10 * 10 * 5 cm2 on the water
      phantom with 400 MeV/u of carbon beam. The transvers plane on the target was
      scanned by 3mm of step size. And, the optimized weighting factors of transverse
      scanning were obtained by MINUIT fitting package of ROOT. An aluminum ridge
      filter was designed to generate 5 cm of physical SOBP through step shape, which
      was optimized through in-house iteration method and the MINUIT package.The
      simulation was performed with Geant4 through applying the transverse scanning
      with the obtained weighting factor and the designed ridge filter. RESULTS: The
      uniformity on the transverse plan will be expected below 4% when it considered
      scattered beam. Also, the uniformity for longitudinal plane will be expected
      lower then 5%. CONCLUSIONS: This preliminary computational study was shown a
      possibility of using ridge filter for acceptable 3 dimensional uniformity on
      active beam delivery system in carbon beam therapy line. The optimization process
      to reach an acceptable uniformity on clinical use should be followed. In
      addition, it would be used for the design of treatment planning system software
      for KIHMA project.

PMID- 28517292
TI  - SU-E-T-313: Probe-Type Experimental Dosimetry in Terms of Absorbed Dose to Water
      in Photon-Brachytherapy a Proposal for a Radiation-Quality Index.
AB  - PURPOSE: In photon-brachytherapy (BT), all data for clinical dosimetry (e.g., the
      dose-rate constant) are not measured in water, but calculated, based on MC
      simulation. To enable the measurement of absorbed dose to water, DW, in the
      vicinity of a source, the complex energy-dependence and other influence
      quantities must be considered. METHODS: The detectors response, R=M/D, is
      understood as product of a detector-material dependent 'absorbed dose response',
      Ren, and Rin, the 'intrinsic response'. Ren is described by the Burlin-theory and
      because of dissimilarities between the detector-material and water, will have
      energy dependent correction factors which convert Ren into the clinically
      relevant DW,Qo=MQo * ND,W,Qo. To characterize BT- source-types, we propose a new
      'radiation-quality index' QBT=Dprim(2cm)/Dprim(1cm), the ratio of the primary
      dose to water at r=2cm to that at the reference distance r=1cm, similar to
      external beam dosimetry. Although QBT cannot be measured directly, it can be
      derived from primary and scatter separated dose-data, published as consensus data
      e.g., in the Carlton AAPM-TG-43-database. RESULTS: Mean QBT-values are: for nine
      HDR and four PDR 192Ir-sources: 0.2258+/-0.5%; one 169Yb- source: 0.2142; and one
      125I-source: 0.1544. CONCLUSIONS: The main benefit of this new QBT-concept is
      that a type of BT-dosimetry-detector needs to be calibrated only for one
      reference radiation-quality, e.g., for Q0=192Ir. To measure the dose for
      different source-types, DW can be determined using calculated radiation-quality
      conversion factors kQ,QoBT, to be included in the AAPM-database and to be
      provided by the manufacturer for each detector-type. Typical BT-dosimetry
      detectors are plastic scintillation detectors, radiochromic film,
      thermoluminescence detectors, optically stimulated detectors, and small volume
      ionization chambers. Recently, different DW(1cm)-primary standards have been
      developed in several European NMIs, enabling to calibrate BT-radiation- sources
      and BT-dosimetry-detectors and allowing to verify MC-calculated dose-rate
      constant values. The proposed definition of QBT has to be discussed
      internationally to find broad consensus.

PMID- 28517294
TI  - SU-E-T-304: Evaluation of Mammosite Multi-Lumen Rotation and Its Dosimetric
      Consequences.
AB  - PURPOSE: To evaluate the dosimetric impact of MammoSite Multi-Lumen (MSML)
      rotation in phantom and patient studies. METHODS AND MATERIALS: A MSML phantom
      with an asymmetric dose distribution was created. Target volume coverage and dose
      at a fixed point 1 cm from the MSML were evaluated as functions of rotation about
      three orthogonal axes (where the origin was set at the center of the MSML and
      axis one ran along the central catheter). Additionally, for three MSML patients
      that were set-up by aligning the stem of the MSML to skin marks, CT scans were
      acquired before each fraction. Rotation about three axes and maximum point dose
      to skin and chestwall were evaluated. RESULTS: In phantom, 10 degrees  rotations
      about the central, second, and third axes give average absolute point dose
      changes with respect to the maximum dose of 1.9%, 3.7%, and 4.2%, respectively;
      and changes in PTV coverage of 0.9%, 1.0%., and 0.8%, respectively. For patients
      1-3 the average absolute rotation about the central axis was 13.60, 9.50, and
      7.20, respectively; axis two was 7.00, 3.20, and 11.40, respectively; axis three
      was 2.90, 2.90, and 3.80, respectively. For cases 1-3 the average absolute change
      per fraction in maximum point dose to the skin was 0.29 Gy, 0.14 Gy, and 0.39 Gy,
      respectively; to the chestwall was 0.17 Gy, 0.20 Gy, and 0.21 Gy, respectively.
      CONCLUSION: Phantom studies showed change in point dose and PTV coverage for a 10
      degrees  rotation about the central catheter yields < 2% variance. Patient data
      indicates skin mark alignment is capable of positioning the MSML with 10 degrees 
      accuracy about the central axis. Thus, central axis rotation can be adequately
      accounted for by skin mark alignment. However, review of the patient data shows
      that rotations about the other axes are equally important and should be
      considered and managed.

PMID- 28517295
TI  - SU-E-T-293: The Potential Application of High Energy Proton Beam-Induced Positron
      for PET Imaging Technique.
AB  - PURPOSE: An existing nuclear interaction cross-section of a positron emitter was
      used to predict range accuracy of proton beams and cross section of the positron
      emitters detected by the PET scanner Methods: To achieve this goal, a MLIC
      phantom was irradiated to 2Gy dose using 124.61MeV, 143.08MeV and 155.25MeV
      proton beam corresponding to the depths of 6.88cm, 10cm and 16cm, respectively,
      in the phantom. The activity produced in each phantom was examined by PET scanner
      within a couple of minutes post-irradiation. Hence, activity signal produced
      along the activated depth dose profile was recorded. In this project, the isotope
      production cross section for carbon from Landolt-Bornstein (1973) has been
      utilized. RESULTS: A good correlation (about 95%) between the positron emission
      and the isotope cross section of the carbon was observed. Consistency between the
      induced activity and the carbon isotope cross section occurred mainly at the
      distal aspect of the fall off zone of both relative cross-sections (i.e. between
      60 - 100%). These results were obtained using the high relative abundance of
      carbon (i.e. 70%) in the phantoms.Conclusions The ranges measured by the depth
      dose profiles and positron emission profiles were in good agreement at the distal
      fall off edge. Furthermore, it is confirmed that the interaction cross-sections
      of individual elements in the tissues could be used to determine the range
      accuracy of the proton depth dose profiles. None Applicable.

PMID- 28517296
TI  - SU-E-T-319: Monte Carlo Characterization of a New Directional Pd-103 High Dose
      Rate Source for Brachytherapy Application.
AB  - PURPOSE: Standard brachytherapy sources emit radiation in a non-preferential
      direction away from the source. Though treatment outcomes are good, this can lead
      to late skin and subcutaneous toxicities in sensitive structures. Proposed low
      dose rate directional sources for interstitial brachytherapy, showed to have an
      improvement in the dose uniformity within the subcutaneous volume, reduction in
      skin dose, and reduction in volume receiving dose outside the target. The
      objective of this work is to demonstrate the potential use of a new Pd-103
      directional seed for application in high dose rate brachytherapy treatments.
      METHODS: Monte Carlo simulations were performed using the MCNP5 F6 energy
      deposition tallies as well as the MCNP5 F4 flux density tallies placed around a
      partially shielded Pd-103 source at angles(deg): 0, 45, 90, 135, 180, 225, 270,
      315 as well as radial distances (cm): 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10.
      The source that modeled was a Pd-103 core using TG-43U recommended nuclear data,
      with a diameter = 1.4 mm, active length = 1.0 cm. In addition osmium metal with
      .03 mm thickness was used as shielding material to cover half of the cylindrical
      surface of the Pd-103 volume. The seed was encapsulated using .05 mm thick
      titanium. RESULTS: MCNP models show that the dose to the radial distances,
      corresponding to the osmium shielded side, are dramatically reduced to less than
      4% of the total dose. CONCLUSIONS: The potential of a Pd-103 directional
      brachytherapy source has been studied. The results show that a seed with a
      partially shielded volume can be exploited to reduce side effects associated with
      radiation therapy to sensitive structures surrounding target volumes.

PMID- 28517297
TI  - SU-E-T-265: Reducing Pacemaker Doses with a Lead Sheet: A Multi-Detector Study.
AB  - PURPOSE: Evaluate the usability of lead shielding to reduce the dose to
      pacemakers. The efficiency and risk of this type of skin block will be presented.
      METHODS: A solid water phantom was used and all measurements were made at a depth
      of 0.5 cm for 6 MV and 23 MV photon beams. Measurements were performed with a
      parallel plate ion chamber and with a plastic scintillation detector (PSD)
      prototype. Measurements were made for fields of 10, 20 and 30 cm square. For
      every field, measurements were made in increment of 5 cm from the center of the
      field to the edge of the 60 cm long phantom for anterior and posterior beams. All
      measures have been made with and without a 1.6 mm of lead shielding wrapped in a
      thermoplastic. RESULTS: For all measurements, both detectors agree to 0.6%, well
      within the uncertainties of the detectors. With antero-posterior fields, the
      benefit of shielding is more important at 23MV (reduction of dose by65%) compared
      to 6MV (reduction of dose by 46%) when the shielding is out of the field. For
      distances larger than 35 cm, no benefits are measured. In the case were the lead
      is completely inside the fields, the dose is increased by the presence of
      shielding. The same observation is made for postero-anterior fields. For
      shielding out of field, the dose is slightly increased. CONCLUSIONS: The used of
      lead shielding with antero-posterior field is advised and provided an easy way to
      decrease dose to pacemaker. For a postero-anterior field, it is preferable to
      avoid shielding, but it could be used if it stays outside fields in the case of a
      multiple beams treatment. PSD has been shown to be an excellent candidate for in
      vivo monitoring dose to pacemakers and also site like foetus.

PMID- 28517298
TI  - SU-E-T-275: Dose Verification in a Small Animal Image-Guided Radiation Therapy X
      Ray Machine: A Dose Comparison between TG-61 Based Look-Up Table and MOSFET
      Method for Various Collimator Sizes.
AB  - PURPOSE: To verify the accuracy of TG-61 based dosimetry with MOSFET technology
      using a tissue-equivalent mouse phantom. METHODS: Accuracy of mouse dose between
      a TG-61 based look-up table was verified with MOSFET technology. The look-up
      table followed a TG-61 based commissioning and used a solid water block and
      radiochromic film. A tissue-equivalent mouse phantom (2 cm diameter, 8 cm length)
      was used for the MOSFET method. Detectors were placed in the phantom at the head
      and center of the body. MOSFETs were calibrated in air with an ion chamber and f
      factor was applied to derive the dose to tissue. In CBCT mode, the phantom was
      positioned such that the system isocenter coincided with the center of the MOSFET
      with the active volume perpendicular to the beam. The absorbed dose was measured
      three times for seven different collimators, respectively. The exposure
      parameters were 225 kVp, 13 mA, and an exposure time of 20 s. RESULTS: For a 10
      mm, 15 mm, and 20 mm circular collimator, the dose measured by the phantom was
      4.3%, 2.7%, and 6% lower than TG-61 based measurements, respectively. For a 10 *
      10 mm, 20 * 20 mm, and 40 * 40 mm collimator, the dose difference was 4.7%, 7.7%,
      and 2.9%, respectively. CONCLUSIONS: The MOSFET data was systematically lower
      than the commissioning data. The dose difference is due to the increased scatter
      radiation in the solid water block versus the dimension of the mouse phantom
      leading to an overestimation of the actual dose in the solid water block. The
      MOSFET method with the use of a tissue- equivalent mouse phantom provides less
      labor intensive geometry-specific dosimetry and accuracy with better dose
      tolerances of up to +/- 2.7%.

PMID- 28517299
TI  - SU-E-T-308: Dosimetry of a New Minimally Invasive Episcleral Brachytherapy
      Device.
AB  - PURPOSE: Describe the dosimetry of an episcleral brachytherapy device. METHODS:
      The SMD-I device is designed to treat exudative age-related macular degeneration
      (AMD) and employs a Sr-90/Y-90 source encapsulated in a stainless steel cylinder.
      The source is welded to a flexible wire allowing it to travel from a shielded
      vault in the SMD-I handle to the distal end of a curved cannula to deliver a
      therapeutic dose of radiation through the sclera to the neovascular target in the
      subchoroidal space. The SMD-I handle and vault are comprised of Ultem, a
      lightweight radiation tolerant plastic, which shields the surgeon. Dose
      calculations were performed using the MCNPX radiation transport code. The
      absolute dose rate was determined using radiochromic film (GAFChromatic(c) MD-55)
      at a point in solid water 2.0mm from the source center perpendicular to the
      cannula. Dose rates at several depths were measured using Kodak EDR2 film in
      water equivalent phantoms to compare with the absolute dose rate measurement and
      MCNPX calculations. The surgeon's hand dose received while manipulating the
      device with the source in the vault was measured using standard TL
      (thermoluminescence) finger ring dosimeters, TL ChipstratesTM, and calculated
      with MCNPX. RESULTS: The absolute dose rate 2.0mm from the source center is 0.45
      Gy/min/mCi. The EDR2 film results agree with the absolute dose measurement and
      the MCNPX calculations. The dose rate decreases rapidly with depth so that the
      dose at the target depth (3mm) is approximately 8 times less than at 1mm depth
      (sclera). The dose distribution is sensitive to the angle between the cannula and
      the neovascular plane. Both TL methods yield a maximum dose rate of 6 MUSv/min
      mCi to the surgeon's fingers consistent with the MCNPX calculation. CONCLUSIONS:
      The SMD-I device permits accurate delivery of a therapeutic radiation dose for
      the treatment of exudative AMD. Russell J. Hamilton is a founder and currently
      serves on the Scientific Advisory Board of Salutaris Medical Devices, Inc.
      Wendell Lutz and Thomas Cetas serve on the Scientific Advisory Board of Salutaris
      Medical Devices, Inc. All authors have received financial support from Salutaris
      Medical Devices, Inc.

PMID- 28517300
TI  - SU-E-T-269: The Evaluation of Copper as an Alternative for Cerrobend Electron
      Shielding.
AB  - PURPOSE: To evaluate the replacement of Cerrobend by copper for electron beam
      cutouts. METHODS: The dosimetric comparisons for circular copper-and Cerrobend
      cutouts with diameters (1.0, 2.0, 3.0, 5.0, 7.5, 10.0, and 12.5 cm) were made
      using electron beams with energies (6, 9, 12, 16, and 20 MeV) from 3 Varian
      accelerators. A PTW Farmer chamber (0.125cc-volume) was used for larger cutouts
      (diameters > 2cm), and an electron-diode for the 2 smallest cutouts. Also a
      Markus parallel plate chamber was used. RESULTS: (1) The tests showed little
      difference for the electron dosimetric characteristics, Eo, Eop, R50, Rp, and
      dmax. For larger cutout, the parameters were virtually the same for copper and
      Cerrobend. for smaller cutout (diameter = 3cm), small discrepancies were observed
      i.e. differences < 1mm for R50, Rp and dmax, =0.1MeV for Eop, and =0.3MeV for Eo.
      (2) The larger-cutout outputs at dmax were also virtually the same (difference =
      0.6%). For smaller cutouts (diameters = 3cm), the copper outputs were 2.0%~5.0%
      higher than Cerrobend. (3) For lower energy electrons (<12MeV), more larger-angle
      scattered electrons from higher-Z Cerrobend raise the Cerrobend percentage-depth
      dose (PDD) curve at shallow-depths, and more forward scatter dose after dmax from
      lower-Z copper shifts the copper PDD slightly away from the one of Cerrobend. for
      higher energy electrons (= 12MeV), the shallow-dose difference becomes smaller
      for both cutouts, but even more forward-scattered dose from copper shifts
      copper's PDD further away from Cerrobend's. (4) The higher X-ray transmission
      through copper is also observable; i.e. 12%, 10%, and 7% for 20MeV, 16MeV, and
      12MeV, respectively, but such small transmitted amount is clinically
      insignificant. CONCLUSIONS: Except for a higher x-ray transmission, other
      dosimetric differences brought in by the replacement of Cerrobend by copper
      cutout are negligible.

PMID- 28517301
TI  - SU-E-T-279: A Novel Electron-Beam Combined with Magnetic Field Application for
      Radiotherapy.
AB  - PURPOSE: The new beam and delivery system consists of an electron accelerator and
      a system of magnets (one or more). Introducing a transverse magnetic field in and
      near the tumor, causes the electrons to spiral in this region, thereby producing
      an effective peak in the depth dose distribution, within the tumor volume.
      Although the basic idea is not new, we suggest here for the first time, a viable
      as well as a workable, magnetic field configuration, which in addition to
      focusing the beam does not interfere with its propagation to the target. METHODS:
      The electron accelerator: can be a linear accelerator or any other type electron
      accelerator, capable of producing different electron energies for different
      depths and dose absorption accumulation. The Field size can be as small as a
      pencil beam and as big as any of the other standard field sizes that are used in
      radiotherapy. The scatter filter can be used or removed. The dose rate
      accumulation can be as higher as possible.The magnets are able to produce
      magnetic fields. The order, direction, width, place, shape and number of the
      magnetic fields define the shape and the Percentage Depth Dose (PDD) curve of the
      electron beam. Prototypes were successfully tested by means of computer
      simulation, using:COMSOL-Multiphsics for magnetic fields calculations. FLUKA
      package, for electron beam MC simulation. RESULTS: Our results suggest that by
      using an electron beam at different energies, combined with magnetic fields, we
      could modify the delivered dose. This is caused by manipulating the electron
      motion via the Lorentz force. The applied magnetic field, will focus the electron
      beam at a given depth and deposit the energy in a given volume and depth, where
      otherwise the electron energy will have spread deeper. The direction and
      magnitude of the magnetic fields will prevent the scattering of the electron beam
      and its absorption in remote volumes. In practice, we get a pseudo Bragg peak
      depth dose distribution, applying a relatively low cost system. The therapeutic
      efficiency induced by the system is of similar efficiency as the ion beam therapy
      techniques. CONCLUSIONS: Our novel concept demonstrates treatment that is almost
      similar to proton therapy and in some parameters even better performance.Unlike
      the current high-energy electron therapy, our system's beam deposit almost all of
      its energy on its target, with a low amount of radiation deposited in tissues
      from the surface of the skin to the front of tumor, and almost no "exit dose"
      beyond the tumor. This property will enables to hit tumors with higher,
      potentially more effective radiation doses, while being considerably less
      expensive.

PMID- 28517302
TI  - SU-E-T-301: A Novel Daily QA Device for Proton Therapy.
AB  - PURPOSE: We describe the design and use of a daily QA device for proton therapy.
      The device is designed for therapists to check the readiness of the IBA Proton
      Therapy System (IBA, Louvain-la-Neuve, Belgium) during morning QA. The checks
      include connectivity, positioning, mechanical, imaging and dosimetric parameters
      of the proton therapy system. METHODS: The device consists of a commercial QA
      device, (rf-DailyQA3 -Sun Nuclear Corporation, Melbourne, FL), in conjunction
      with a home-made acrylic phantom and mechanical indexing jig. The indexing jig
      indexes the rf-DailyQA3 to treatment couch. Fiducial markers embedded in the
      phantom are used for checking the x-ray image and alignment accuracy of the
      imaging system (VeriSuite, MedCom, Darmstadt- Germany). The rf- DailyQA3 is used
      to check the proton beam output, range and symmetry, which are acquired during
      one single beam delivery of 100 monitor units. We developed in-house software to
      calculate the variation of beam range and symmetry, based on readings from the
      various ion chambers inside the rf-DailyQA3. RESULTS: The device has been
      employed to perform daily QA since June 2010 at two operational proton treatment
      centers and will soon be implemented at ProCure's New Jersey center. All QA tests
      are performed by radiation therapists and reviewed by the medical physicist on
      duty. Due to the simplicity of the device and the associated processing software,
      the QA time is less than 20 minutes per room. The measurement data collected by
      the device during daily QA are recorded in the OIS. The integrity of the data is
      validated by comparing against other independent measurements. CONCLUSIONS: The
      daily QA device has been proven to be robust, reliable and user-friendly. The
      performance of this system has been proven to be stable and accurate using trend
      analyses. Key words:proton therapy, daily QA, output, range, symmetry.

PMID- 28517303
TI  - SU-E-T-233: Evaluation of Superficial Doses for Postmastectomy Radiotherapy.
AB  - PURPOSE: To measure and to evaluate the surface and superficial doses for
      patients requiring postmastectomy radiotherapy (PMRT) with different treatment
      techniques. METHODS: An elliptic cylinder cork and super-flab boluses were used
      to simulate the lung and the chest wall, respectively. Sets of CT images with
      chest wall thicknesses of 5, 8, 10, 13, and 15 mm were acquired. Hypothetical
      clinical target volumes were outlined and modified to fit a margin of 1 -3 mm
      away from the surface. The planning target volume was initially created by
      expanding an isotropic 3 mm margin from CTV and then a margin of 1-3 mm was
      shrunk from the phantom surface. Treatment techniques using a pair of tangential
      wedged fields (TWF) and 4-field IMRT were designed with a prescribed fraction
      dose (Dp) of 180 cGy. Superficial dose profiles around the phantom circumference
      at depths of 0, 1, 2, 3, and 5 mm were obtained for each treatment technique
      using radiochromic external beam therapy (EBT) films. RESULTS: The TWF plans show
      a dose buildup about 3 mm at the median and lateral tangential incident regions
      with a surface dose of about 52% of Dp. Dose profiles were more uniform in the
      PTV region for the 4-F IMRT plans. Most of the PTV region had doses higher than
      94% of Dp at depths larger than 1 mm. The mean surface dose was about 65% of Dp
      for the 4-F IMRT plans. The maximum dose for the 4-F IMRT plans was less than
      118.4% of Dp. CONCLUSIONS: The dose variations caused by the oblique incidence
      and a thin chest wall are modulated and reduced in the IMRT plans. More uniform
      dose distributions within the PTV are obtained with the 4-F IMRT plans.

PMID- 28517304
TI  - SU-E-T-226: Clinical Implementation of a Gravity-Oriented Wedge for Total Body
      Irradiation.
AB  - PURPOSE: To describe a TBI technique designed within the limits of a small-room
      geometry and its clinical implementation. METHODS: Following construction of the
      universal treatment devices, including the double-wedge, beam spoiler table, and
      patient support table, commissioning consists of measurements to determine the
      output, tissue-phantom ratio, effective source distance, and off-axis factor.
      Dose is calculated by applying these factors per patient-specific measurements to
      arbitrary point in the patient. Typically, ten calculation points are located at
      mid-separation along the mid-sagittal plane from the head to the ankles. When
      areas of unacceptably high dose are calculated, custom compensators are
      constructed from 5-mm sheets of PMMA and placed over the patient on top of the
      beam spoiler table. The typical dose homogeneity of the planning calculations is
      within 2% of the prescribed dose. RESULTS: To verify the accuracy of the
      technique, an anthropomorphic phantom was simulated and treated. In total, 128
      thermoluminescent dosimeters (TLDs) were irradiated within the phantom.
      Concentrations of TLDs were located in the planes of selected calculation points,
      i.e. the head, neck, sternum, lung, umbilicus, and pelvis. Results showed the
      average dose to these locations differed from the intended dose by -3.5%, 3.4%,
      2.6%, 9.5%, 2.8%, and 0.5%, respectively. Due to its heterogeneous material, a
      higher discrepancy in the lung dose was anticipated. To demonstrate the
      dosimetric size of the radiation field, ionization chamber measurements were
      taken on one lateral side of the treatment area at a constant depth of 5 cm. A
      few measurements on the contralateral side were within 1 %, verifying the field's
      lateral symmetry. The approximate treatment area for the current technique is
      approximately 180*50 cm. CONCLUSIONS: We have demonstrated a small-room technique
      capable of meeting the dosimetric goal of TBI. To improve the dosimetric
      characteristics, new universal treatment devices are currently being designed and
      constructed.

PMID- 28517305
TI  - SU-E-T-254: Quantitative Evaluation of Three Mathematical Models for Radiation
      Induced Secondary Cancer Risk for Lung in Stereotactic Body Radiotherapy.
AB  - PURPOSE: Several mathematical models exist to predict secondary cancer risks from
      radiotherapy treatment. In this study, we aimed to compare three dosimetry-based
      models in the application of stereotactic body radiotherapy (SBRT) of early-stage
      non-small cell lung cancer (NSCLC) with three radiotherapy treatment modalities.
      METHODS: Ten patients who received definitive SBRT for early-stage NSCLC were
      retrospectively selected. for each patient, a helical tomotherapy (HT) plan, a
      three-dimensional conformal radiotherapy (3D-CRT) plan, and a volumetric
      modulated arc therapy (VMAT) plan were generated to deliver 50 Gy to the planning
      target volume in five fractions. The excess absolute risk (EAR) for secondary
      lung cancer occurrence was calculated using three risk models: the linear
      exponential model, the plateau model, and the linear model. The sensitivity of
      the EAR to the prescription dose was evaluated by varying the prescription dose
      in the range of 40 to 60 Gy. RESULTS: Based on the linear-exponential model, the
      average EAR's (in occurrences per 10,000 patients per year) were 8.4+/-2.7, 8.3+/
      2.1, and 8.4+/-1.9 for the HT plans, 3D-CRT plans, and VMAT plans respectively
      with 40 Gy prescription dose, and 9.4+/-2.5, 9.0+/-2.1, and 9.3+/-1.8 with 60 Gy.
      Based on the plateau model, the average EAR's were 10.7+/-3.9, 10.6+/-3.0, and
      10.9+/-2.8 with 40 Gy, and 12.9+/-4.2, 12.6+/-3.4, 12.9+/-3.1 with 60 Gy. Based
      on the linear model, the average EAR's were 29.1+/-13.4, 29.4+/-11.4, and 30.0+/
      11.1 with 40 Gy, and 43.8+/-20.1, 44.0+/-11.0, 45.1+/-16.6 with 60 Gy. The
      difference in EAR's were not statistically significant among the HT, 3D-CRT, and
      VMAT plans. CONCLUSIONS: Three secondary cancer risk models, as well as three
      SBRT treatment modalities, were compared. There was no significant difference in
      secondary lung cancer risks among the three treatment modalities in this study.

PMID- 28517306
TI  - SU-E-T-239: In Vivo Dosimetry with Surface Diodes during Total Body Irradiation:
      A Patient Thickness Factor to Correct Midline Dose.
AB  - PURPOSE: In vivo dosimetry (IVD) assessment of treatment dose is important when
      delivering total body irradiation (TBI). One method is to average AP and PA
      surface diode measurements and compare them to prescribed midline doses. We
      designed phantom studies to examine the impact of patient thickness on surface
      IVD measurements under TBI conditions. METHODS: Phantom studies were designed to
      assess the effects of patient thickness on diode IVD. Sun Nuclear QED diodes with
      inherent buildup were placed on anterior and posterior surfaces of a solid water
      phantom. Phantom thickness was varied between 20 and 40 cm. A PTW farmer chamber
      was inserted in the center of the phantom at 425 SSD to reflect prescribed
      midline dose, and 50 cGy was delivered to midline with 18 MV photons. Averaged
      entrance and exit diode doses were then compared to farmer chamber measurements
      of phantom midline dose. RESULTS: A trend of increased deviation with increasing
      umbilicus thickness was observed between averaged surface diodes and midline
      farmer chamber measurements. Averaged surface diode dose ranged from 49.6 cGy (20
      cm thickness) to 52.1 cGy (40 cm thickness). Interpolation of diode measurements
      to midline resulted in linear overestimation of delivered dose relative to farmer
      chamber measurements at midline, up to 6.8% at 40 cm umbilicus thickness.
      CONCLUSION: Accurate in vivo dosimetry at time of patient TBI is important to
      allow individual correction of MU exposure and tissue compensation. Without
      patient thickness correction, overresponse of surface diodes may lead to
      unnecessary clinical intervention to treatment MU or compensation and
      insufficient midline dose. Additionally, SAD setup is preferable to SSD setup to
      minimize thickness non-linearity. In conclusion, thickness correction factors
      should be used to generate expected diode readings for patients with thickness
      greater than 30 cm.

PMID- 28517307
TI  - SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose
      Range Dependency of Radio-Biological Parameters.
AB  - PURPOSE: Introducing an extended, phenomenological, generalized equivalent
      uniform dose (eEUD) that incorporates multiple volume-effect parameters for
      different dose-ranges. METHODS: The generalized EUD (gEUD) was introduced as an
      estimate of the EUD that incorporates a single, tissue-specific parameter - the
      volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its
      radio-biological equivalency to a given inhomogeneous dose distribution is not a
      priori clear and mechanistic models based on radio-biological parameters are
      assumed to better resemble the underlying biology. However, for normal organs
      mechanistic models are hard to derive, since the structural organization of the
      tissue plays a significant role. Consequently, phenomenological approaches might
      be especially useful in order to describe dose-response for normal tissues.
      However, the single parameter used to estimate the gEUD may not suffice in
      accurately representing more complex biological effects that have been discussed
      in the literature. For instance, radio-biological parameters and hence the
      effects of fractionation are known to be dose-range dependent. Therefore, we
      propose an extended phenomenological eEUD formula that incorporates multiple VEPs
      accounting for dose-range dependency. RESULTS: The eEUD introduced is a piecewise
      polynomial expansion of the gEUD formula. In general, it allows for an arbitrary
      number of VEPs, each valid for a certain dose-range. We proved that the formula
      fulfills required mathematical and physical criteria such as invertibility of the
      underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD
      as a special case, if all VEPs are equal to 'a' from the gEUD model. CONCLUSION:
      The eEUD is a concept that expands the gEUD such that it can theoretically
      represent dose-range dependent effects. Its practicality, however, remains to be
      shown. As a next step, this will be done by estimating the eEUD from patient data
      using maximum-likelihood based NTCP modelling in the same way it is commonly done
      for the gEUD.

PMID- 28517308
TI  - SU-E-T-218: The IHE-RO Helper Tool: Demonstrating the Connectivity Issues Solved
      by IHE-RO.
AB  - PURPOSE: To develop a Web-based application (IHE-RO Helper) to allow
      comprehensive review of the interconnectivity and interoperability of various
      radiotherapy devices established through testing sanctioned by the Integrating
      Healthcare Enterprise-Radiation Oncology (IHE-RO). MATERIAL AND METHODS: IHE-RO
      is an initiative sponsored by ASTRO to improve the way computer based systems in
      radiation oncology share information using well-defined data exchange standards
      (DICOM / HL7). At the IHE-RO Connectathon events over the last 4 years, 11
      vendors with 14 different products have successfully tested and identified
      solutions to connectivity problems in treatment planning, simulation and
      delivery. Because the test results are highly technical, the interconnectivity
      issues amongst the RT devices may get overlooked by the end users. The IHE-RO
      helper tool is designed to operate in simple clinical terms with queries and
      presentations organized based on treatment techniques and clinical features that
      are familiar to the practitioners. For example, if you are planning to purchase a
      treatment planning system capable of generating plans (e.g. Stereotactic
      treatments) and are concerned whether the TPS can successfully transfer such data
      to your treatment management system (TMS) and subsequently to your treatment
      delivery system (TDS), the IHE-RO Helper can identify the connectivity
      requirements and list vendors that have successfully passed an IHE-RO
      Connectathon and validated their solution to the specific requirements. RESULTS:
      The IHE-RO helper tool provides a graphical and textual user interface to
      effectively demonstrate the solved interconnectivity problems between TPS, TMS
      and TDS. A report is also provided that explains the interconnectivity problems
      and its solutions. CONCLUSIONS: The IHE-RO helper is an effective tool to clearly
      identify vendor products that are IHE-RO compliant, thereby encourages vendor
      participation in testing and validation. Such a tool will be invaluable in
      procurement of new equipment to ensure a priori interoperability with anticipated
      RT devices deployed in the clinic. This research and development project is
      supported by the Bankhead-Coley Cancer Research Program grant # RC1-09BW-09
      26833.

PMID- 28517309
TI  - SU-E-T-258: Assessment of Radiation Induced Second Cancer Risks in Proton Therapy
      and IMRT for Organs inside the Main Radiation Field.
AB  - PURPOSE: Radiation therapy can potentially cause a second malignancy. There is
      clinical evidence that those occur typically within the beam path in the
      medium/high dose region. The purpose of this study was to assess the risk for
      developing a radiation induced tumor within the treated volume and to compare
      this risk for proton therapy and IMRT. METHODS: Fully contoured age and gender
      specific whole body phantoms (4-year and 14-year old) were uploaded into a
      treatment planning system and typical tumor volumes were contoured based on
      patients treated for optic glioma and vertebral body Ewing's sarcoma. Lifetime
      attributable risks (LARs) for developing a second malignancy were calculated
      using a risk model incorporating factors for cell kill, mutations, repopulation,
      and inhomogeneous organ doses. RESULTS: For standard fractionation schemes, the
      LAR for developing a second malignancy from radiation therapy alone were found to
      be up to 2.7% for a 4-year old optic glioma patient treated with IMRT considering
      a soft tissue carcinoma risk model only. Sarcoma risks were found to be below 1%
      in all cases. For the 14-year old, risks were found to be about a factor of 2
      lower. For the Ewing's sarcoma cases the risks based on the sarcoma model were
      typically higher than the carcinoma risks, i.e. up to 1.3% LAR for soft tissue
      sarcoma. Generally, the risk from proton therapy turned out to be lower by a
      factor of 2 to 10. However, comparison of a 3-field and 4-field proton plan shows
      that the distribution of the dose, i.e., the particular treatment plan, plays a
      role as well. CONCLUSIONS: In general, proton therapy can significantly reduce
      the risk for developing an in-field second malignancy. Risk analysis based on our
      formalism could be applied within treatment planning programs to guide treatment
      plans for pediatric patients. Federal Share of program income earned by
      Massachusetts General Hospital on NIH/NCI C06 CA059267.

PMID- 28517310
TI  - SU-E-T-228: The Beauty and the Beast: Transition from Film/paper Charts to
      Paperless Environment with a New TrueBeam/ARIA System in a Small Community
      Hospital on a Tight Budget.
AB  - PURPOSE: To review the issues a physicist may encounter in a community hospital
      during the transition from film/paper charts to a paperless environment with ARIA
      and a TrueBeam LINAC. With a lean budget, it was necessary for the physics group
      to take on the project management responsibilities in order save costs. This work
      highlights the lessons learned during the planning and execution of our project.
      METHODS: Like many hospitals around the county, our hospital was caught in the
      economic downturn and was unable to provide all of the capital necessary to
      upgrade to the radiation oncology department. However, with the support of the
      hospital foundation, a total of $6M was secured for new LINAC, ARIA and CT
      simulator. To save costs on facilities and computers, it was necessary for the
      physics group to be involved in creating architectural drawings for shielding
      calculations, finding a vendor to remove the old linac, assisting the foundation
      to raise money, submission of the 'Certificate of Need' approval with the state,
      negotiation with vendors, IT infrastructure, reviews with the general contractor
      and vendor's project team, and ultimately writing the commissioning reports for
      the new systems as well as developing new policies and procedures. RESULTS:
      During a period of 4 months, the old LINAC was removed, facility renovations
      made, the TrueBeam linac was installed, accepted, and commissioned and first
      patients were treated. In addition, we transitioned from a film/paper environment
      to a paperless environment. However, this was very stressful for staff and it may
      be advisable to stage such a project over a longer period of time. There was also
      significant lost revenue (~$2M) during downtime of construction, installation,
      and commissioning. CONCLUSIONS: The radiation oncology department was upgraded
      (The Beauty) on a tight budget but at the cost of added stress (The Beast) to the
      staff.

PMID- 28517311
TI  - SU-E-T-243: Dosimeter Parameters Comparison of TrueBeam, Trilogy, and IX
      Machines.
AB  - PURPOSE: Besides flattening-filter-free beams, Varian TureBeam Linac also has
      conventional flattened photon beams. In our facility, we have TrueBeam, Trilogy
      and iX machines from Varian; they all have same energy specifications: 6 and 10
      MV photon beams, as well as 6, 9, 12, 16 and 20 MeV electron beams. This study is
      to compare the photon and electron beams dosimeter parameters among the three
      machines. METHODS: Beam data (including PDDs, inline and crossline profiles at
      various field sizes and various depths) were collected using Sun Nuclear
      Dosimetry 3D Scanner with nominal 100 cm SSD setup. These data were post
      processed using Sun Nuclear Dosimetry software, including normalization,
      interpolation and smoothing. The ion chambers used for scanning are IBA CC13.
      RESULTS: Photon beams: The percentage depth doses with field sizes of 4*4, 6*6,
      10*10, 15*15, 20*20, 30*30 and 40*40 cm * cm of 6 MV and 10 MV photon beams from
      the three machines are very close. Compared with Varian Golden Beam Data, the
      maximal variation of PDDs at depths of 5, 10, 15, 20, and 30 cm is 1.0%, with
      mean value 0.6% and standard deviation 0.28% for 6 MV; for 10 MV beams, they are
      2.0% (at depth of 30 cm), 0.9%, and 0.48% respectively. Also, the three machines
      have very similar beam profiles; the profiles' shoulder, penumbra and umbra match
      well for both inline and crossline beam profiles at various field sizes and
      various depths.Electron beams: As compared the percentage surface doses (0.5 mm
      from the surface), dmax, R90, R80, R50, and R30 of electron beams with energy of
      6, 9, 12, 16, and 20 MeV at 10 cm cone, the electron beams of TrueBeam and iX are
      almost identical. CONCLUSIONS: The 6 and 10 MV photon beam data of TrueBeam,
      Trilogy, and iX have a same variation range when comparing with Varian Golden
      Beam Data.

PMID- 28517312
TI  - SU-E-T-212: Clinical Deployment of an Automatic Planning Interface for Overlap
      Volume Histogram Based Treatment Planning.
AB  - PURPOSE: To develop and deploy an interface to support automatic treatment
      planning which predicts achievable dose levels for organs at risk (OARs) from
      patients with similar or more complicated anatomies queried from a database. This
      interface will provide an easy to use method of selecting the best known
      achievable dose values for a given patient, and use them to automate the planning
      process. METHODS: An overlap volume histogram (OVH) describes the distance a
      target structure can be expanded with the volume of the compared overlap
      structure. An OVH is generated for each target/critical structure pair and stored
      in a database with dose-volume histograms (DVHs) for each patient. For all
      patients, structures are consistently named by mapping ROI names to a set of
      common names. For a new patient, the patient database is queried for the lowest
      achievable dose for each OAR from patients in the database with the same or lower
      overlap distance. The plan parameters and generated objectives are then
      automatically loaded into treatment planning system for optimization. The final
      clinical plan from each patient is added to the database to improve the results
      of future queries. RESULTS: The system has been accepted by the dosimetrists for
      clinical use. Automatically generated plans required less dosimetrist interaction
      to achieve similar coverage to manually generated plans while OAR doses were
      reduced or no worse than the manually generated plans. CONCLUSION: Automatic
      planning tools can aid dosimetrists in quickly generating plans which maintain
      target coverage and produce comparable or reduced dose to OARs. Our interface has
      simplified the process enabling the broader use of the system across our
      dosimetry staff. Philips stock ownership Philips Sponsored Research Elekta
      Sponsored Research Elekta Patent License Accuray (Tomotherapy) Patent License.

PMID- 28517313
TI  - SU-E-T-252: Consolidating Duodenal/Small Bowel Toxicity Data via Iso-Effective
      Dose Calculations Based on Compiled Clinical Data.
AB  - PURPOSE: To consolidate duodenal toxicity data from clinical studies with
      different dose fractionation schemes using the modified linear quadratic (MLQ)
      model. A methodology of adjusting the dose-volume parameters todifferent levels
      of normal tissue complication probability (NTCP) was proposed and used to
      estimate dose-volume constrains for treatment planning. METHODS: A set of
      modified Lyman model parameters for duodenum NTCP were estimated by the chi
      squared fitting method using tolerance dose and equivalent uniform dose (EUD)
      data obtained in a literature search. These model parameters were then used to
      convert the dose-volume pair, (D, V) to the iso-effective dose (in 2 Gy per
      fraction)- volume pair, (DMLQED2, V). A relationship was derived to convert a
      given DMLQED2 at one level of NTCP, to an iso-effective dose at another NTCP.
      RESULTS: The literature search yielded six reports useful in making estimates of
      small bowel/duodenal toxicity. The modified Lyman model parameters were found to
      be TD50 = 60.9 +/- 7.9 Gy, m = 0.21 +/- 0.05, and I = 0.09 +/- 0.03 Gy-1. The
      toxicity rates associated with hypo-fractionated radiotherapy (HBRT) were found
      to be consistent with other clinical data of conventional fractionations found in
      the literature. The conversion of DMLQED2 between different NTCP levels remains
      consistent with each other over a narrow range of NTCP. CONCLUSION: MLQ based iso
      effective calculations of dose-response data corresponding to Grade > 2 toxicity
      were found to be consistent with one another within the uncertainty of DMLQED2
      due to model parameter uncertainty. The dose-volume data that can be converted to
      different NTCP levels may be used to estimate duodenal/small bowel dose-volume
      constrains for new dose fractionation and/or dose escalation strategies. Medical
      College of Wisconsin Cancer Center Meinerz Foundation.

PMID- 28517314
TI  - SU-E-T-221: Evaluation of Technology Using Probabilistic Decision Models.
AB  - PURPOSE: Medical physicists are often asked to evaluate or choose
      appropriatetechnology for clinical applications. These are
      multidimensionalproblems that also suffer from different degrees of uncertainty
      in thevariables. Probabilistic decision models are a robust andmathematically
      correct means of handling these issues. The principlesof constructing such models
      are presented along with practicalexamples in the areas of IGRT, IMRT and proton
      therapy. METHODS: Influence diagrams are used to model the variables and
      theiruncertainties and include action and reward variables. Influencediagrams are
      directed acyclic graphs that use Bayesian probabilitycalculus to propagate
      probabilities and to update prior probabilitiesin the presence of evidence. An
      influence diagram was used to modelthe question of whether brain tumors are
      better treated with x-rayIMRT or proton therapy, with or without CT-guided
      localization. Datafor the conditional probabilities of the model were obtained
      from theliterature and included models of TCP, NTCP and induction of
      secondmalignancies, as well as data on the probability density functions
      forinterfraction patient motion. Dosimetric data were obtained using theCMS
      treatment planning system. RESULTS: Several different tumor types and sites were
      studied. The critical variables in the model were identified andstudied using
      analyses of evidence, parameters and value ofinformation. The impact of imaging
      was significant, regardless of theradiation type. The models used in determining
      some of theconditional probabilities parameters also played an important role
      inranking alternatives. CONCLUSIONS: Although such choices are difficult,
      physicists mustproceed with the best data at hand. Without a rigorous framework
      onwhich to build a model of the process, decisions are likely to be based
      onunstated assumptions and incorrect inference. The example ofcomparing
      irradiation modalities for brain tumors shows the power ofinfluence diagrams in
      this critical context.

PMID- 28517315
TI  - SU-E-T-262: Treatment Room Activation after 15 MV Single Fraction Radiation
      Treatments Delivered Using Varian's TrueBeam and Trilogy Linear Accelerators.
AB  - PURPOSE: To measure radiation levels in treatment room due to activation after
      15MV single fraction radiation treatment (SFRT) delivered to a solid water
      phantom. METHODS: We performed radiation surveys of two LINAC treatment rooms
      immediately after 15 MV SFRT. We delivered a sequence of two 15 MV single
      fraction IMRT treatments to a phantom at the end of a typical treatment day. The
      first treatment delivered was 6201MU (about 12 Gy) and the second one, 15 minutes
      later was 12711 MU (24 Gy). Both were delivered to the pelvic region of a solid
      water anthropomorphic phantom. In a second technique, a 15 MV VMAT SFRT (4326 MU)
      was delivered using the Varian TrueBeam LINAC. Radiation measurements were
      recorded repetitively at four locations using a thin windowed Geiger Muller
      detector, a sodium iodide photon spectrometer and a pressurized ionization
      chamber. The four locations surveyed were: the top of the collimator head, the
      collimator window surface, the isocenter, and the inferior end of the patient
      support assembly. RESULTS: Radiation levels at the isocenter at the end of the
      treatment day and before the two IMRT SFRTs varied from 0.06 to 0.1 mR/h. Within
      2-3 minutes after finishing the second IMRT SFRT the radiation levels were
      approximately 10 and 1.4 mR/h at isocenter for the TrueBeam and Trilogy rooms
      respectively and around 0.6 mR/h for the TrueBeam VMAT SFRT. Closing the MLC and
      the jaws significantly reduces the radiation level at isocenter. The average half
      life of the mixture of radionuclides produced is about 10 minutes. CONCLUSIONS:
      High dose single fraction IMRT treatments with 15 MV photons produce elevated
      treatment room activation as compared to conventional IMRT. In addition,
      activation levels varied between the TrueBeam and Trilogy for similar SFRT
      schemes. There is no funding support, disclosures, or conflict of interest.

PMID- 28517316
TI  - SU-E-T-232: Proton Source Modeling for Geant4 Monte Carlo Simulations.
AB  - PURPOSE: To investigate the effect of initial proton beam source placement,
      distribution and angle on the proton dose distribution in a therapeutic nozzle
      using Geant4. METHODS: We performed Geant4 Monte Carlo simulations of a passively
      scattered proton treatment nozzle. Accurate geometry including all elements in
      the treatment room was used. Protons were generated just inside the vacuum pipe
      using one of two models. First, a standard two dimensional Gaussian distribution
      of proton starting position was used with a small random angle added to the
      initial direction. The size of the Gaussian distribution and the random angle
      were set to match measured beam spot size and angular spread at the exit window.
      Second, a point source of protons further back in the vacuum pipe with a small
      random angle was used. The distance of the point source to exit window and the
      random angle were set to match the spot size and angular deviation used for the
      Gaussian distribution. Depth dose curves and orthogonal beam profiles were
      examined to determine changes between the two models. RESULTS: Orthogonal beam
      profiles for large apertures showed changes of up to 6.5% between the two models
      with the point source showing much better agreement with measured data. Depth
      dose curves and orthogonal profiles for small apertures were unaffected. For
      large apertures, the average difference compared to measured data was of 1.9% and
      0.7% and the max difference was 5.0% and 1.6% for Gaussian and point sources,
      respectively. CONCLUSIONS: The point source more realistically models the proton
      distribution in the vacuum pipe by correlating the proton position with the
      direction. For certain scattering setups and large apertures point source
      modeling is necessary to accurate match measured data with Monte Carlo
      simulations.

PMID- 28517317
TI  - SU-E-T-206: Standardization in Documentation Format Can Significantly Reduce
      Manual Data Entry Error in Patient Chart.
AB  - PURPOSE: To demonstrate that standardization in documentation format can
      significantly reduce manual data entry error in patient chart. METHOD AND
      MATERIALS: Due to lack of direct data link between CT on rail imaging
      registration software and patient R&V system, therapists have to manually enter
      translation correction of patient position into R&V system after performing
      imaging registration between CT image taken just before treatment delivery and
      treatment planning CT image. Approximately six months after CT on rail was placed
      into clinical service, we started requiring therapists to use a standard format
      to document the shifts when they manually enter data to reduce manual data entry
      error rate. The therapist manual data entry errors in R&V system before (551
      entries) and after the format standardization (1645 entries) are the subjects of
      statistical analysis. The errors are divided into two categories (recoverable and
      non-recoverable errors) depending on whether a human being can recover the
      translation shifts in lateral, longitudinal, and vertical directions from the
      therapist notes. Fisher's exact test is performed to test the statistical
      significance of therapist's data entry error reduction after our imposing the
      documentation format requirement. Temporal information on when the errors were
      made is also analyzed to find out when errors are more likely to happen. RESULTS:
      Statistical analysis indicated that reductions in the numbers of recoverable, non
      recoverable, and total errors after standardization in document format are all
      statistically significant with p values less than 0.05. CONCLUSION: A simple and
      low cost measure like standardization in document format can significantly reduce
      the errors operators introduce to patient R&V system when they perform manual
      data entry. We hope our experience will convince people to follow more
      disciplined documentation rule to reduce the error rate and therefore potentially
      can improve the quality of patient care when manual data entry is involved.

PMID- 28517318
TI  - SU-E-T-216: TPS QC Supporting Program by a Third-Party Evaluation Agency in
      Japan.
AB  - PURPOSE: To equalize the quality of radiation therapy in Japan by supporting
      quality control of radiation treatment planning system. METHODS: Center for
      Cancer Control and Information Service in National Cancer Center supports the QA
      QC of the cancer core hospitals in Japan as a third-party evaluation agency.
      Recently, a program for assessing the quality of treatment planning system (TPS)
      began as a part of our QA-QC supporting activities. In this program, a
      questionnaire about TPS was sent to 45 prefectural cancer core hospitals in
      Japan. The object of this questionnaire is to assess the proper commissioning,
      implement and applications of TPSs. The contents of the questionnaire are as
      follows; 1) calculate MUs which deliver 1000 cGy to the point of SSD = 100 cm, 10
      cm depth with field sizes ranging from 5*5 to 30 * 30 cm2 , and obtain doses at
      several depths for the calculated MUs, 2) calculate MUs which deliver 1000 cGy to
      the point of SSD = 100 cm, 10 cm depth for wedge fields whose angles are from 15
      to 60 degrees, and obtain doses at several depths with the MUs, 3) calculate MU
      which deliver 1000 cGy to the point of STD = 100 cm, 10 cm depth with 10*10 cm2
      field size and obtain doses at several depths with the MU. RESULTS: In this
      program, 179 beam data from 44 facilities were collected. Data were compared in
      terms of dose per MU, output factor, wedge factor and TMR. It was found that 90%
      of the data agreed within 2%. CONCLUSIONS: The quality of the treatment planning
      system was investigated through the questionnaire including the information of
      essential beam data. We compared 179 beam data in TPSs sent from 44 facilities
      and 90% of the data showed good agreement.

PMID- 28517319
TI  - SU-E-T-225: A Comprehensive Evaluation of Real-Time Motion Tracking of a Surface
      Imaging System for Lung Treatment.
AB  - PURPOSE: Applicability of the AlignRT surface imaging system was extensively
      investigated for real-time motion tracking in radiation therapy of lung cancer.
      METHODS: A 4D computer-controlled motion phantom was employed to simulate a human
      breathing motion. An anthropomorphic thoracic phantom (a coronal cross-sectional
      area: ~1,200 cm2 ) was monitored during the 4D motion tracking. A breathing cycle
      from a healthy subject (breathing frequency: 0.2 Hz; maximum amplitude: vertical
      7 mm, longitudinal 6 mm, and lateral 1.2 mm) was monitored and fed into the
      phantom control system. The real time monitoring was investigated by modifying a
      region of detection (the whole, a half, and a quarter of the area) and
      combination of 3 cameras (patient left, middle, and right). RESULTS: The real
      time tracking errors (detected breathing motion - the input of the subject's
      breathing) of the phantom motion using one camera (lateral, longitudinal,
      vertical) were (0.02+/-0.14 mm, -0.23+/-0.48 mm, -0.10+/-0.48 mm) with
      ipsilateral halves of the area (frame rate: 1.52 Hz), (0.06+/-0.10 mm, -0.30+/
      0.30 mm, -0.03-0.35 mm) with ipsilateral quarters (frame rate: 1.95 Hz), and
      (0.19+/-0.96 mm, 0.29+/-1.50 mm, -0.46+/-1.58 mm) with contralateral quarters
      (frame rate: 3.04 Hz). The detection errors using 2-camera combinations (left
      middle and right-middle) were (-0.06+/-0.06 mm, -0.43+/-0.21 mm, 0.00+/-0.22 mm)
      for the ipsilateral quarters and (-0.62+/-0.18 mm, -1.20+/-0.37 mm, 0.03+/-0.30
      mm) for the contralateral quarters, respectively. The 3-camera tracking using
      halves of the area presented an error of (-0.04+/-0.12 mm, -0.69+/-0.35 mm, 
      0.08+/-0.38 mm) with a frame rate of 0.62 Hz. CONCLUSIONS: To guarantee a sub
      millimeter accuracy of realtime motion tracking in the lung treatment,
      combination of 2 cameras or less, a frame rate of greater than the Nyquist
      frequency (in this study fN = 2B (breathing frequency) = 0.4 Hz), and a tracking
      area of less than an ipsilateral half of thoracic area is highly recommended.

PMID- 28517320
TI  - SU-E-T-236: Brachytherapy for Breast Cancer Patients with Implanted Pacemeker,
      Using Multi Lumen Partial Breast Applicator.
AB  - PURPOSE: Discuss optimised Accelerated Partial Breast Irradiation (APBI) using a
      Strut-Adjused Volume Implant (SAVI) applicator for patients with implanted
      pacemeker, without overdosing or relocating the pacemaker. METHODS: A right
      breast cancer patient with an in situ pacemaker (Medtronic model ADDR01) on the
      right side underwent breast conservative surgery and was referred for Partial
      Breast Irradiation (PBI) using Ir-192 High Dose Rate Brachytherapy. Preliminary
      estimation of the pacemaker dose from a pre-insertion CT study was about 8 % of
      the prescribed dose which exceeded the generally accepted dose of 2Gy. The
      challenge was to use a suitable applicator to treat the tumor bed and 1cm margin
      without exceeding the 2Gy limit to the pacemaker and the leads. A seven catheter
      SAVI device was selected and implanted in the right breast in an optimal
      direction and a 3D treatment plan was generated following a post insertion CT
      scan, using the Oncentra Brachy treatment planning system. Optimization tools
      namely anatomy based Inverse Planning Simulated Annealing (IPSA), and graphical
      optimization were utilized to load and optimize the dwell time in the catheters
      and reduce the dose received by the pacemaker. Device interrogation was conducted
      before and after the treatment. All operational parameters of the pacemaker were
      found to be normal.No change in the baseline reference values were observed.
      RESULTS: Using the SAVI device it was possible to limit the pacemaker/ leads dose
      to less than 2 Gy. Target V100, V95 and V90 were 90.1%, 95.5% and 98.5%
      respectively. V150 and V200 being 18.6cc and 10.6cc respectively.Calculated
      average point doses on pacemaker assembly for ten fractions was 140cGy.
      CONCLUSIONS: By combining the optimization tools of today's Brachytherapy
      planning system and a multilumen SAVI applicator, HDR partial breast irradiation
      can be safely delivered for breast cancer patients with in situ pacemaker, with
      out the fear of interrupting pacemaker functionality.

PMID- 28517321
TI  - SU-E-T-253: Assessing Small-Volume Cord Biological Effective Dose for Repeat
      Spinal Stereotactic Body Radiotherapy Treatments.
AB  - PURPOSE: Small-volume biologically effective (BED) dose limits are critical to
      safe spinal stereotactic body radiotherapy (SBRT) delivery. However, due to
      mismatch in spatial location of dose hot spots from non-uniform dose
      distributions inherent to SBRT, for repeat treatment courses they cannot be
      simply added by assuming a uniform dose distribution. This study aims to develop
      a probability-based biological equivalent dose formula to solve this problem.
      METHODS: A generalized biological equivalent dose (gBED) was formulated via
      computing damaging or survival probability of repeat spine SBRT treatments.
      Parameters from the linear-quadratic model such as alpha/beta =2 Gy for the
      spinal cord were applied for the gBED calculations. The derived method was
      applied to both simulated and clinical treatment cases to demonstrate its
      applicability and usefulness for assessing spinal cord dose limits for repeated
      SBRT treatment courses. RESULTS: The gBED formula allows direct superposition of
      dose within a small volume of spinal cord from a non-uniform dose distribution of
      varying dose fractionation schemes of SBRT. From the studied examples,
      traditional BED calculations even with full voxel-by-voxel tracking calculations
      resulted in inconsistent BED values and can underestimate the biological dose to
      a small-volume spinal cord by as much as 20%. Such an error tends to increase
      rapidly with increasing volume of interests such as from 0.1 mL to 2.0 mL.
      CONCLUSIONS: When assessing spinal cord tolerance for repeat spinal SBRT
      treatments, consistent surrogates such as gBED are needed to avoid potential
      underestimation of treatment-induced complications.

PMID- 28517322
TI  - SU-E-T-238: Annual QA of Proton Gantry with Robotic Table.
AB  - PURPOSE: To perform the annual QA of proton gantry with a robotic table. METHODS:
      A new proton gantry with robotic table has been commissioned and is being used in
      clinic for patient treatment. The gantry is equipped with a robotic table with 6
      degrees of freedom and dual cardinal angle KV imagers for patient registration.
      The system allows direct movement from one beam location to another without
      additional image registration, which effectively reduces portal setup time and
      increases treatment efficiency. The annual QA has four main components: Beam
      parameter checks included proton depth dose, output, linearity, modulation
      factor, field size factor, effective source distance, compensator gap factor, and
      monitor unit comparison between model calibration and physical measurements for
      every energy. Mechanical checks included gantry and robotic table isocenter,
      gantry and robotic couch isocentricity, and mechanical movement of fully loaded
      couch and corresponding digital readout. Imaging system checks included proton, X
      ray beam, laser and image receptor alignment, image quality of KV imagers, and
      image registration accuracy. The last were the system safety checks. Methods used
      to perform these checks, especially those pertaining to robotic positioner will
      be discussed. RESULTS: The new proton gantry and robotic table had the isocentric
      accuracy of about 1 mm. The accuracy of mechanical movements of the robotic table
      was within 1mm/0.5 degree in the clinical motion range. The accuracy of proton
      outputs determined by IAEA TRS 398 protocol was within +/-2% and the consistency
      of beam range for all clinical energies at cardinal gantry angles was within 1mm.
      CONCLUSIONS: The results of the gantry annual QA demonstrate that the machine
      satisfies the highest standards of quality assurance for proton radiation
      treatment. The annual QA verifies the proton output, robotic table movement
      accuracy, image registration and safety of the machine and thus increases our
      confidence level in the uncertainties of daily proton treatments.

PMID- 28517323
TI  - SU-E-T-247: Dose-Volummetrics in the Prediction of Pulmonary Function Changes
      after Radiotherapy in Patients with Non-Small Cell Lung Cancer.
AB  - PURPOSE: This aim was to explore the relationship between dose-volummetrics and
      changes of pulmonary function tests (PFTs) and provide criteria of dose
      volummetrics to predict these changes of PFTs after radiotherapy with NSCLC.
      METHODS: Between March 2008 to November 2009,39 patients (male 30,female 9,
      median age 66 years) with inoperable NSCLC received definitive 3DCRT or IMRT
      treatment were included in this study. The GTV included primary tumor and
      metastasis lymph node in hilar or mediastinum, and delineated the PTV from GTV
      1.5 to 2.0 centimeter outside. The prescription doses ranged from 60-68Gy with a
      median dose of 66Gy. The forced vital capacity(FVC), forced expiratory volume in
      one second (FEV1.0) and diffusion capacity of carbon monoxide(DLCO) were checked
      for each patient two times, one week pretreatment and 2 to 4 months after
      radiotherapy. dose-volummetrics of lungV10,V15,V20,V25,V30,V35,V40, lung mean
      dose and GTV100,GTV95, GTV90,GTV80 were analyzed. Statistical methods of Pearson
      and Line regression were used to determine whether correlation existed between
      these metrics and the changes in PFTs. RESULTS: This investigation showed that
      FVC went down 2.4+/-1.6 from 77.2+/-18.7 to 74.1+/-18.5, FEV1.0 went down 5.9+/
      3.2 from 74.1+/-20.5 to 70.9+/-20.2 P=0.065and DLCO went down 17.9+/-6.3 from
      70.4+/-20.5 to 59.8+/-16.0 P=0.000 after radiotherapy. No correlation was found
      between dose-volummterics and the changes in PFTs. Excluding patients(n=15)with
      pretreatment atelectasis, significant correlation was retained between dose
      volummetrics (lungV20,V25,V30,V35,V40, Lung mean dose and Veff) and the PFTs
      changes (P=0.05).Multivariate analysis showed that lung V30 was risk factor for
      the changes of FEV1.0 and DLCO(P=0.046 and 0.041).Furthermore analysis by
      stratifies, compared lung V30=18% and <18%, the dropped values of FVC, FEV1.0,
      DLCO were 6.9+/-2.5 and 4.5+/-1.8 P=0.061, 15.2+/-4.0 and 6.1+/-2.3 P=0.033,
      22.8+/-2.0 and 11.6+/-1.4 P=0.000 respectively, showed PFTs became more worse
      with lungV30=18%. CONCLUSIONS: lungV30 is risk factor to affect PFTs changes in
      patients with NSCLC excluding those who have had pretreatment atelectasis. Our
      funding support received from National Natural Science Foundation of China
      (30870743).

PMID- 28517324
TI  - SU-E-T-257: Risk of Radiogenic Second Cancer after Photon and Proton Craniospinal
      Irradiation.
AB  - PURPOSE: To compare proton and photon therapies in terms of the risks of second
      cancers for a pediatric medulloblastoma patient receiving craniospinal
      irradiation (CSI). METHODS: Two CSI treatment plans with 23.4 Gy or Gy (RBE)
      prescribed dose were computed for a 4-year-old boy withmedulloblastoma: a three
      field 6-MV photon therapy plan and a four-field proton therapy plan. The primary
      doses for both plans were determined using a commercial treatment planning
      system. Stray radiation doses for proton therapy were determined from Monte Carlo
      simulations, and stray radiation doses for photon therapy were determined from
      measured data. The dose-risk model based on Biological Effects of Ionization
      Radiation VII report was used to estimate risk of second cancer. RESULTS:
      Baseline predictions of the relative risk of each organ were always less for
      proton CSI than for photon CSI after various follow-up years for the patient. The
      lifetime risks of the incidence of second cancer after proton CSI and photon CSI
      were 7.7% and 92%, respectively, and the ratio of lifetime risk was 0.083.
      Uncertainty analysis revealed the qualitative findings of this study were
      insensitive to any plausible changes of dose-risk models and mean neutron
      radiation weighting factor. CONCLUSIONS: Proton therapy confers lower predicted
      risk of second cancer for the pediatric medulloblastoma patient compared with
      photon therapy.

PMID- 28517325
TI  - SU-E-T-227: Re-Evaluation of Dose Distribution and Margins for IMRT Prostate
      Plans.
AB  - PURPOSE: To evaluate the dose distribution on prostate and proximal seminal
      vesicles (SVs), rectum, and bladder when a certain geometry uncertainty is
      occurred during planning or delivery, and further determine the optimistic margin
      relation to different directions. METHODS: Thirty prostate cancer patients with
      prostate specific antigen (PSA) less than 10 and Gleason Score between 2 and 6
      have been selected and planned in EclipseTM 10.0 treatment planning system. PTV
      is expanded from GTV (prostate plus proximal SVs) with uniform 6 mm margin in all
      directions. All patients are head-first-supine and planned with seven beam IMRT
      technique. At least 95% of PTV is covered by full prescription. Rectum V65 is
      less than 17%, rectum V40 is less than 35%, bladder V65 is less than 25%, and
      bladder V40 is less than 50%. To simulate the deviation from planning error or
      setup uncertainty, the original isocenter of each plan has been shifted every 2mm
      from 0mm to 10mm in superior (S), inferior (I), right (R), left (L), anterior
      (A), and posterior (P) directions. The dose is then re-calculated with fixed jaw
      technique. The new plan parameters such as PTV coverage, both bladder and rectum
      V65 and V40 are analyzed. RESULTS: PTV full dose coverage is linearly decreasing
      with increasing isocenter shift and the absolute slope mean values are 2.2, 2.2,
      3.0, 2.7, 2.0, and 2.0 corresponding to S-I-P-A-L-R directions. As for rectum and
      bladder, the further away from the shifted isocenter, the smaller values of V65
      and V40. CONCLUSIONS: This study shows that 2 to 3 percentage of decrements on
      PTV full dose coverage occurs while prostate target shifts every millimeter. To
      uniformly cover the dosimetric impact uncertainty, it shows that the optimistic
      margin ratio would be 1.1(S):1.1(I):1.5(P):1.35(A):1(L):1(R) for the six
      directions.

PMID- 28517326
TI  - SU-E-T-242: Effect of Skull Surgical Clips and Bone Artifacts on Treatment
      Planning for Brain Tumors with Proton Beam.
AB  - PURPOSE: To study the effect of skull surgical clips and bone artifacts on dose
      distribution using proton beams for treatment planning. METHODS: Proton treatment
      plans with double scattering technique for ten patients were generated on
      patients with brain tumors having had prior surgery with skull bone surgical
      clips. Appropriate clinical, dosimetric and geometric margins were added for each
      tumor volume and dose was prescribed to clinical target volume (CTV). The CT
      images used for treatment planning show streaking artifacts due to the clips and
      there are also soft artifacts on tissue adjacent to skull bone due to high
      density of bone. We performed two plans for each patient; a plan without
      correcting for artifacts and a second plan replacing the artifacts with normal
      tissue. For the second plan, the artifacts were contoured and a CT numbers
      obtained by sampling pixels in adjacent areas without artifacts was assigned to
      the contours. We compared the two plans by evaluating the dose volume histogram
      (DVH) for tumor coverage and the mean, median, and maximum dose for normal tissue
      structures. RESULTS: Volume of CTV receiving 99% of the prescribed dose (PD) show
      a mean difference of 3% higher dose for artifact corrected plans. The normal
      tissue structures comparison shows and average dose difference of 5%, 8%, 11%,
      and 30% lower doses for optical chiasm, temporal lobes, brain and optic nerves
      for artifact corrected plans respectively. CONCLUSIONS: In general when using
      artifact correction for surgical skull clips and skull bone, the tumor coverage
      tends to be slightly higher. Overall, the normal tissue structures tend to have
      lower doses depending on the volume, position and the geometry for artifact
      corrected plans. We recommend the correction of artifacts due to surgical clips
      and skull bone for brain region proton planning.

PMID- 28517327
TI  - SU-E-T-211: Peer Review System for Ensuring Quality of Radiation Therapy
      Treatments.
AB  - PURPOSE: To demonstrate a Web-based electronic peer review system that has the
      potential to improve quality of care for radiation therapy patients. The system
      provides tools that allow radiation oncologists to seek peer review of target and
      critical structure delineation, treatment plans, and share clinical data with
      peers to optimize radiation therapy treatments. MATERIAL AND METHODS: Peer review
      of radiation therapy treatment planning data prior to its initiation improves the
      quality of radiation therapy and clinical outcomes. Web-based access to radiation
      therapy treatment planning data and medical records mitigate existing
      geographical and temporal constraints. With internet access, the healthcare
      provider can access the data from any location and review it in an interactive
      and collaborative manner. Interoperability standard like DICOM-RT and IHE-RO
      compliant RT Systems have facilitated the design and implementation of PRS with
      Silverlight Web technology, .net Framework and SQL Server. Local DICOM-RT archive
      and cloud based services are deployed to facilitate remote peer reviews. RESULTS:
      To validate the PRS system, we tested the system for 100 patients with Philips
      Pinnacle v 9.0 and Varian Eclipse v 8.9 treatment planning system (TPS). We
      transmitted the DICOM RT data from the TPS to the cloud based services via the
      PRS local DICOM RT Archive. Various CT simulation based parameters such as
      orientation of CT, properties of RT structures etc. were compared between the TPS
      and PRS system. Data integrity of other parameters such as patient demographics
      (patient name, ID, attending physician etc.) and dose volume related parameters
      were also evaluated. Such rigorous testing allowed us to optimize the
      functionalities and clinical implementation of the PRS. CONCLUSIONS: We believe
      that the PRS will improve the quality and safety of a broad spectrum of radiation
      therapy patients treated in underserved areas while discouraging the
      overutilization of expensive radiation treatment modalities. This research and
      development project is supported by the James and Ester King Biomedical Research
      Program grant # RC1-09KW-09-26829.

PMID- 28517328
TI  - SU-E-T-251: Analysis of Irradiated Induced Lung Injury in Non-Small Cell Lung
      Cancer (NSCLC) Treated by Three-Dimensional Conformal Radiotherapy(3DCRT).
AB  - PURPOSE: The aim of this study was to analyze the affect factors with radiation
      induced lung injury of NSCLC treated by 3DCRT, in order to supply reference
      criteria for optimize the treatment planning, further to improve the local
      control rate and the quality of life of NSCLC patients. METHODS: From August 2000
      to December 2004, 107 NSCLC patients received 3DCRT were retrospectively enrolled
      in this study. All of patients received the prescription doses ranged from 60
      68Gy with a median dose of 66Gy. Dosimetric parameters of dose-volume histograms
      from 3DCRT plans was recorded. The lung injury were assessed for each patient
      during the treatment and follow-up within 3 months after treatment completion.
      Acute radiation induced pneumonitis were graded by one radiation oncologist
      according to the RTOG/EORTC criteria. The correlation between dosimetric
      parameters with lung injury was evaluated by univariate and multivariate analysis
      using Logistic Regression Model of SPSS11.0 software. RESULTS: In the 107
      patients of NSCLC, the rate of irradiated induced lung injury was 62.6% and the
      rate of =2 grade radiation induced pneumonitis was 38.3%. Twenty-three cases were
      classified in grade 2, fourteen cases in grade 3, four cases in grade 4.
      Univariate analysis showed chronic obstructive pulmonary disease(COPD), number of
      beams field, lung mean dose, lung V5-V40 were important parameters on radiation
      induced lung injury. The rate of =2 grade lung injury was 56.3%(18/32) in
      patients accompany COPD, compared with 30.7%(23/75) of those without COPD. In the
      same way,the rate of =2 grade lung injury was 61.9%(26/42) in patients of lung
      mean dose=20Gy, which higher than 19.4%(12/62) of lung mean dose<20Gy. Further
      more, lung mean dose, lung V20 and COPD were likely to be the independent factors
      of radiation induced lung injury by Logistic Regression Model. CONCLUSIONS: lung
      mean dose, lung V20 and COPD were the independent affect factors on irradiated
      induced lung injury. Our funding support received from National Natural Science
      Foundation of China (30870743).

PMID- 28517329
TI  - SU-E-T-261: Determination of Initial Exposure Rates and Clearance Constants in a
      Sequence of 165 Consecutive Thyroid Cancer Patients Undergoing NaI-131 Therapy.
AB  - PURPOSE: Following surgery, papillary and follicular thyroid cancers are usually
      treated with oral administration of NaI-131. In order to estimate subsequent
      staff, family, and public exposures, it is important to measure both exposure
      rates as well as the time of clearance of residual activity from these
      individuals. There is the additional possibility that patient whole-body absorbed
      dose estimates may be made using the data. METHODS: During the historical
      interval 2006 - 2010, a total of 165 consecutive thyroid cancer patients were
      assayed at the time of activity administration and over the following several
      days. Using a calibrated radiation detector, exposure rates at one meter from the
      navel were measured between 2 and 5 times before release. By using these
      measurements and assuming a single-exponential clearance, we were able to
      evaluate initial exposure rates as well as the biological rate constant [k(biol)]
      for clearance of I-131 from the body. RESULTS: Regression analyses were used to
      fit the initial exposure [X(0)] results as a function of administered activity.
      By least-squares, the slope was determined to be 0.15 mR/h/mCi over a clinically
      determined activity range of 25 to 250 mCi. At a given activity, there was wide
      variation of X(0) due to individual factors such as amount of residual thyroid
      mass and body habitus. For example, at 150 mCi, X(0) varied from 15 to 35 mR/h at
      one meter with the average being 25 mR/h. For the 165 patients, the mean
      biological clearance constant was 0.049/h. CONCLUSION: Average initial exposure
      rates at one meter from 165 NaI-131 patients have been determined. The biological
      clearance was seen to be much more rapid than the physical decay constant for I
      131 (0.0036/h). At a given activity level, variation of exposure rates was
      approximately +/- 40% over the corresponding patient population.

PMID- 28517330
TI  - SU-E-T-231: Comparison of Beam Characteristics of Small Field 6 MeV Electrons as
      Replacement for Superficial X Ray Beam.
AB  - PURPOSE: To compare beam characteristics of superficial X-rays with 6 MeV
      Electrons for the purpose of replacing superficial treatments with electron
      fields for skin lesions. METHODS: Electron beam cutouts were made with 12mm
      thickness cerrobend in diameters 2-5 cm to match superficial X-ray machine cones.
      Central axis depth doses and profiles were generated using 0.007 cc Exradin A-16
      ion chamber, in PTW water phantom at 1mm steps, at 96 and 100cm SSD for electron
      beams, and at 15cm SSD for superficial X-rays. From the beam data, radiation
      penumbra 90-10%, 90% profile width, peripheral dose and percentage depth dose
      were obtained for comparison. RESULTS: The 90-10% radiation penumbra was ranging
      7.4-13.7 mm, 12.6-17.6 mm for 6 MeV electrons at 96 and 100cm SSD respectively,
      and 4.2-11.4 mm for 2-5 cm superficial X-ray cones. For 90% treatment width, a
      margin ranging 5-7 mm, 6-9 mm is needed around the periphery of target for 6 MeV
      Electrons at 96 and 100cm SSD respectively, and 2-3 mm for superficial X-ray
      cones. For 96cm SSD, the peripheral dose from the geometrical field edge were
      3.9% at 1cm and 0.5% at 2cm. It was 2.6% at 1cm and 0.7% at 2cm for 100cm SSD.
      For superficial, it was 6.2%, 7.5%, 9.1% at 1cm, and 3.4%, 4.3%, 5.6% at 2cm for
      100 kV, 120 kV and 150 kV respectively. The electron surface dose was below 90%.
      CONCLUSION: 6 MeV Electron beam shows high superiority with rapid fall off of
      dose beyond target with lower peripheral dose compared to superficial X-rays.
      However, the electrons need higher margin around the target and also need
      appropriate bolus thickness to increase skin dose. The dose at depth beyond 2cm
      makes very significant advantage using electrons compared to superficial X-rays.

PMID- 28517331
TI  - SU-E-T-205: MLC Predictive Maintenance Using Statistical Process Control
      Analysis.
AB  - PURPOSE: MLC failure increases accelerator downtime and negatively affects the
      clinic treatment delivery schedule. This study investigates the use of
      Statistical Process Control (SPC), a modern quality control methodology, to
      retrospectively evaluate MLC performance data thereby predicting the impending
      failure of individual MLC leaves. METHODS: SPC, a methodology which detects
      exceptional variability in a process, was used to analyze MLC leaf velocity data.
      A MLC velocity test is performed weekly on all leaves during morning QA. The
      leaves sweep 15 cm across the radiation field with the gantry pointing down. The
      leaf speed is analyzed from the generated dynalog file using quality assurance
      software. MLC leaf speeds in which a known motor failure occurred (8) and those
      in which no motor replacement was performed (11) were retrospectively evaluated
      for a 71 week period. SPC individual and moving range (I/MR) charts were used in
      the analysis. The I/MR chart limits were calculated using the first twenty weeks
      of data and set at 3 standard deviations from the mean. RESULTS: The MLCs in
      which a motor failure occurred followed two general trends: (a) no data
      indicating a change in leaf speed prior to failure (5 of 8) and (b) a series of
      data points exceeding the limit prior to motor failure (3 of 8). I/MR charts for
      a high percentage (8 of 11) of the non-replaced MLC motors indicated that only a
      single point exceeded the limit. These single point excesses were deemed false
      positives. CONCLUSIONS: SPC analysis using MLC performance data may be helpful in
      detecting a significant percentage of impending failures of MLC motors. The
      ability to detect MLC failure may depend on the method of failure (i.e. gradual
      or catastrophic). Further study is needed to determine if increasing the sampling
      frequency could increase reliability. Project was support by a grant from Varian
      Medical Systems, Inc.

PMID- 28517332
TI  - SU-E-T-215: A Technique for Treating Patients outside the Mosaiq R&V System for
      TrueBeam Users (or 4DTC).
AB  - PURPOSE: When the record and verify (R&V) system (Mosaiq, Elekta Medical Systems)
      is unavailable to send information to the treatment console of the linear
      accelerator (Varian Clinac, Varian Medical Systems), treatment is manually
      delivered by entering parameters into the treatment console and loading backed up
      MLC files. The new linear accelerator, the TrueBeam (Varian Medical Systems)
      lacks the ability to manually deliver treatment by entering machine parameters
      into the treatment console. METHODS: The TrueBeam can only deliver treatments
      using the R&V system or loading DICOM RT plan files directly in File Mode. Every
      time a prescription site is sent from the R&V system to the accelerator, a DICOM
      RT plan file is created by the R&V system. A script was created that reads the
      headers of these files, copies them to the treatment console and renames them in
      an identifiable form. At the end of each treatment day, the script is executed
      transferring only the DICOM RT plan files created that treatment day. A
      contingency report is then generated from the R&V system, which contains machine
      parameters for all fields for all patients under treatment. When the R&V system
      is unavailable the RT plan files are opened in file mode, and the machine
      parameters are verified using the contingency report before delivery. This system
      was tested on a cohort of patients. Each patient's plan was opened in file mode
      and the machine parameters were verified against the patient's planned treatment
      in the R&V system. RESULTS: All files opened in file mode were identical to the
      information stored in the R&V system. This was tested both on the TrueBeam and
      accelerators having the 4DTC. CONCLUSIONS: Our technique was validated and is an
      alternative method for delivering treatment when the R&V system is unavailable.

PMID- 28517333
TI  - SU-E-T-224: Dose Distribution of Oesophagus Stents Measured by EBT2 Film
      Dosimetry.
AB  - PURPOSE: The purpose of this study is to investigate the dose enhancement at
      oesophagus stents made of nitinol. The material is a nickel titan alloy with an
      effective atomic number of 26. Because of the increased atomic number in
      comparison to the human body, dose enhancement in surrounding tissue is expected.
      METHODS: The relative dose distribution around the stent was measured in a water
      phantom. To simulate the air cavity within the oesophagus, a styrodur cylinder
      was placed inside the stent. The stent was held with a circular PMMA holder. An
      EBT2 film was wrapped around the stent to measure the relative radial dose
      distribution.The setup was irradiated with a 6MV photon beam (Siemens Primus) and
      a field size of 5cmx5cm. The distance between source and centre of the stent was
      100cm.The EBT2 films were digitized at a scanning resolution of 72dpi using an
      Epson 10000XL flatbed scanner with a transparency unit. Furthermore, the films
      were fixed in a frame to prevent Newton rings in the scanned image. RESULTS: The
      dose increases in all directions around the stent. With approximately 18%, the
      highest increase is caused on the proximal side of the stent. On the backside the
      dose enhancement is approximately 10%. CONCLUSIONS: Dose enhancements around a
      stent are detectable and one should be aware of it's occurence in the
      radiotherapeutical treatment of oesophageal cancer. Because of the enhancement in
      all directions healthy tissue may be affected.

PMID- 28517334
TI  - SU-E-T-235: Dosimetry Study within a Millimeter from Beam Exiting Air-Tissue
      Interface Using Film and Monte-Carlo Simulation on a Co-60 Beam.
AB  - PURPOSE: Objective is to assess dose accuracy and uniformity to cells in a well
      plate irradiated on Co-60 beam using film (EBT2) and Monte-Carlo simulation.
      METHODS: Situations are encountered where dosimetry near beam-exiting air
      interface is needed. Typical example is irradiation of cells in well-plate. Small
      amount of cell emulsion may amount to as small as 1 mm thickness which results in
      leaving large air space above the cells. Due to contamination concerns, air space
      above cells can not be avoided. Preferred geometry for irradiation is to place
      cell-plate on a build-up slab (water-equivalent), and point the beam upward. On
      Co-60 beam, film EBT2 was employed to measure doses 0.1, 0.4, 0.7, 1.2 mm
      upstream from air- interface. Film optical-density (OD) was measured with a
      pocket densitometer, and converted to dose using film-calibration specific to
      film-batch. To validate film data, Monte-Carlo code DOSXYZNRC was employed for
      simulation. Doses were calculated employing (i) calculation grid 0.1-1.0 mm along
      beam direction, and (ii) 15000 million incident particles to achieve < 0.2%
      precision. RESULTS: Doses measured with film close to beam-exiting air-interface
      are ~16% lower than the maximum doses 1.2 mm up-stream and beyond. Monte-Carlo
      calculations validate the doses measured with film within measurement uncertainty
      (2%). Dose variation is steep in the first 0.1 mm zone near air-interface, but it
      is within 10% further up-stream. CONCLUSIONS: In cell irradiations, dose in
      homogeneity in the top 1mm zone is significant. Layer close to air-interface
      receives ~16% lower dose than the layer 1.2mm up-stream. Dose homogeneity with
      the stated geometry can be improved by having (i) larger amount of cells to
      provide emulsion thickness > 3mm, and (ii) non-homogeneous emulsion for cells to
      settle at the bottom. Since dose in-homogeneity is primarily due to air
      interface, results are expected to be qualitatively similar for other beams (Cs
      137 or 6 MV.

PMID- 28517335
TI  - SU-E-T-208: The Secondary Malignancy Risk Estimation Due to the Neutron
      Contamination in 3D-CRT and IMRT Treatment Techniques by Using Bubble Detectors.
AB  - PURPOSE: In this study, the neutron measurements were performed in free in air
      and RW3 solid water phantom to estimate the secondary malignancy risk for three
      dimensional conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy
      (IMRT) techniques in prostate cancer treatment. METHODS: Neutron dose were
      measured in 18 MV Elekta Synergy Platform and Varian Clinac linear accelerators
      by using bubble detector for personal neutron dosimetry (BD-PND). To determine
      the neutron equivalent dose in different depths and different distance from the
      edge of treatment field RW3 solid water phantom was used and organs location was
      defined in Alderson Rando phantom with respect to target (prostate) position in
      the treatment field. By using these data, we determined the neutron equivalent
      dose and effective dose for the standard prostate cancer patient treated with 3D
      CRT and IMRT with 18 MV photon energy. The total dose was 70 Gy in 3D-CRT and 76
      Gy in IMRT treatment in the current study. For both of these treatment
      techniques, we estimated the risk of secondary malignancies due to the neutron
      contamination by using the International Commission on Radiological Protection
      (ICRP) report 103. RESULTS: The equivalent dose and effective dose due the
      neutron contamination were considerably high in 18 MV IMRT technique. The
      secondary malignancy risk estimation for 3D-CRT and IMRT were found to be 0.44%
      and 1.15% for Elekta Synergy Platform linear accelerator, 0.92% and 2.38% for the
      Varian Clinac DHX High Performance linear accelerator, respectively. CONCLUSIONS:
      Therefore, one should take care of the secondary malignancy risk in case of using
      18 MV in IMRT applications.

PMID- 28517336
TI  - SU-E-T-263: Luminescent Dosimetry to Measure the Out-Of-Field Low and High LET
      Dose Components in High Energy Photon and Proton Therapy Beams.
AB  - PURPOSE: Luminescent dosimetry using thermoluminescent detectors (TLDs) and
      optically stimulated luminescent detectors (OSLDs) were used in mixed radiation
      fields containing both low LET (photons and protons) and high LET
      (neutrons)components to obtain their out-of-field absorbed dose, dose equivalent
      and quality factor. METHOD AND MATERIALS: LiF Thermoluminescent Detectors (TLDs)
      600 and 700 chips with dimensions 0.31*0.31*0.038 cm3 were used in a 25.4 cm
      diameter Bonner sphere centered 42 cm from the isocenter of a 15*x15 cm2 field to
      measure the secondary doses for 10, 15 and 18 MV photons and a 200 MeV proton
      therapy beam. From the sensitivity difference to LET radiation between the210 and
      280 C peaks in the glow curve, the areas under the peaks were used to obtain the
      absorbed dose, dose equivalent and QF of the secondary radiation. The OSLD
      detector measured the low LET dose component to compare with the TLD dose
      measurement. The neutron calibration of the TLDs was obtained from an Am-Be
      source at the Argonne National Laboratory. The photon and proton TLD and OSLD
      calibrations were obtained in 6 MV and 200 MeV beams, respectively. RESULTS: From
      the two-peak analysis of the TLDs in the Bonner sphere the ratios of the neutron
      dose to photon dose were 0.001, 0.014 and 0.17 for 10, 15 and 18 MV,
      respectively. The low LET OSLD measurements agreed within 10% of the TLD results.
      From the dose equivalent measurements the QFs (+/-14%) obtained were 4.5, 3.9 and
      4.0 for these beam energies. For the 200 MeV proton beam the ratio of neutron to
      proton dose was 0.28 with a measured QF of 13. CONCLUSION: Luminescent detectors
      in a Bonner Sphere provide measurements of the secondary photon, proton and
      neutron doses and provide an estimate of the neutron QF.

PMID- 28517337
TI  - SU-E-T-237: Leading 25 in 25: A Bibliometric Analysis of Classics Articles in
      IMRT.
AB  - PURPOSE: Scientific publication in IMRT has experienced significant development
      since its introduction. Bibliometric analyses allow an understanding of how this
      publication trend is organized at an aggregated level. Citation analysis is one
      of the most widely used bibliometric tools of scientometrics. Analysis of
      classics, defined as an articles with 100 or more citations, is common in the
      biomedical sciences as it reflects an article's influence and the recognition it
      receives in its professional and scientific community. Our objective was to
      identify the 25 most frequently cited classic articles in IMRT in the past 25
      years. METHODS: The 25 most-cited IMRT articles were identified by searching
      ISI's Web of Knowledge and Pubmed databases for all related publications from
      1986 through 2011. Articles were evaluated for several characteristics such as
      author(s), institution, country of origin, publication year, type, and number of
      citations. An unadjusted categorical analysis was performed to compare all
      articles published in the search period. RESULTS: Our search yielded a cumulative
      total of 37,197 entries for the publication period. Original research and
      clinical trial articles accounted for 25,827 and 312, respectively, for a total
      of 25,719 entries. The 25 most-cited articles were identified from the latter sum
      and selected out of 123 classics. The number of citations per article ranged from
      203 to 504. IMRT classics appeared in one general and five core journals.
      CONCLUSIONS: This study analyzed publication patterns focused on IMRT, its most
      influential classic articles, journals that published them, their authors and
      other salient characteristics. Such information is of importance to researchers
      and those who wish to study the history and development of the field.

PMID- 28517338
TI  - SU-E-T-256: Radiation Dose Responses for Chemoradiation Therapy of Pancreatic
      Cancer: An Analysis of Compiled Clinical Data Using Biophysical Models.
AB  - PURPOSE: We have analyzed recent clinical data obtained from chemoradiation of
      unresectable, locally advanced pancreatic cancer in order to examine possible
      benefits from radiotherapy (RT) dose escalation as well as to propose possible
      dose escalated fractionation schemes. METHODS: A modified linear quadratic (LQ)
      model was used to fit clinical tumor response data from chemoradiation treatments
      using different fractionations. Biophysical radiosensitivy parameters, a and
      alpha/beta, tumor potential doubling time, Td, and delay time for tumor doubling
      during treatment, Tk, were extracted from the fits and were used to calculate
      feasible fractionation schemes for dose escalations. RESULTS: Examination of
      published data from 20 institutions showed no clear indication of improved
      survival with raised radiation dose. However, an enhancement in tumor response
      was observed for higher irradiation doses, an important and promising clinical
      Result with respect to palliation and quality of life. The radiobiological
      parameter estimates obtained from the analysis are: alpha/beta = 10 +/- 3 Gy, a =
      0.010 +/- 0.003 Gy-1, Td = 56 +/- 5 days and Tk = 7 +/- 2 days. Possible dose
      escalation schemes are proposed based on the calculation of the biologically
      equivalent dose (BED) required for a 50% tumor response rate. CONCLUSIONS: From
      the point of view of tumor response, escalation of the administered radiation
      dose leads to a potential clinical benefit, which when combined with normal
      tissue complication analyses may Result in improved treatments for certain
      patients with advanced pancreatic cancer. Based on this analysis, a dose
      escalation trial with 2.25 Gy/fraction up to 69.75 Gy is being initiated for
      unresectable pancreatic cancer at our institution. Partially supported by MCW
      Cancer Center Meinerz Foundation.

PMID- 28517339
TI  - SU-E-T-241: Proton Range Compared to the Treatment Planning Modeled Range.
AB  - PURPOSE: To compare the range of the protons measured in the treatment room to
      the range predicted by Xio. METHODS: Depth dose curves were measured using a
      multi layer ionization chamber for various ranges and modulations. Ranges and
      modulations were increased in one centimeter increments. The depth dose curves
      were then analyzed and the measured range was determined. The range is defined as
      the point where the distal edge of the depth dose curve is equal to 90% of the
      average value of the dose across the spread out bragg peak. The measured range
      was then compared to the range predicted by the treatment planning system. The
      treatment planning system used was Xio. RESULTS: The maximum deviation was found
      to be 1.6 mm, with the majority of range/modulation combinations falling under 1
      mm. CONCLUSIONS: The difference in range being modeled by the treatment planning
      system compared to the range measured in the teatment rooms is acceptable, and an
      uncertainty of 1.5mm is used for treatment planning.

PMID- 28517340
TI  - SU-E-T-210: Surviving a Visit by the Radiological Physics Center.
AB  - PURPOSE: To demonstrate an objective approach to determining if a negative report
      from the Radiological Physics Center (RPC) of greater than 10% error is valid or
      has clinical significance. METHODS: The discrepancy involved the clinical
      activity (mgRaEq) of Cs-137 sources, some manufactured by 3M and some by
      Amersham. Measurements were made in the proprietary RPC Well Counter calibrated
      by the MD Anderson ADCL and our Well Counter (CNMC, Model 44D) calibrated by the
      same laboratory as well as the University of Wisconsin ADCL. In addition, we
      possess an Amersham Cs-137 Check Source that had been calibrated by the UW-ADCL
      in 2002. All clinical sources were checked in both Well Counters on the first
      visit. One clinical source and the Check Source were measured in a second visit
      that occurred 51 days later. RESULTS: On the initial RPC visit, 9 of 25 sources
      had a minimum of an 8% discrepancy between the RPC and the Institution, with a
      maximum of 11%. Contributing errors included using the incorrect straw position
      by us, an unexplained 2.3% error in the RPC data identified 73 days post-visit, a
      2% variation in Chamber Factors for our Well Counter from the two ADCL's. When we
      use the 2004 value of Air Kerma Strength for the Check Source to determine a
      Calibration Factor of the Well Counter, all sources were within 0.5% of their
      decayed value established in 2002. CONCLUSIONS: This work emphasizes the value of
      having simple Constancy Check systems in a Quality Assurance program as
      'Accuracy' has error bars. The disagreement in calibration data between the ADCL
      Laboratories, which was at the 2% maximum quoted in their Calibration Reports, is
      a reminder that there is uncertainty in measurements. Constancy Checks allow one
      to sort out discrepancies and to answer challenges to the validity of your
      program.

PMID- 28517341
TI  - SU-E-T-250: Dose-Response Curves for the Esophagus.
AB  - PURPOSE: To determine the dose-response curve for the esophagus, using esophageal
      thickening as a surrogate for radiation injury. METHODS: 15 esophageal cancer
      patients were selected who had received weekly 4DCT images throughout their
      course of concurrent chemo-radiotherapy (IMRT) to a total of 50.4Gy. Each patient
      had a length of at least 4cm of esophagus that was outside the GTV but received
      the full prescription dose. The weekly CT images were registered with the
      original treatment planning CT images using deformable registration techniques,
      and the esophagus contours mapped to the weekly images. The relative change in
      esophagus size was calculated as the average ratio of the cross-sectional area of
      the esophagus (minus air) in the weekly images to the area in the planning images
      for a 1cm long region of the esophagus in the center of the CTV (i.e. away from
      the GTV and field edge). We are considering this region to be 'normal esophagus.'
      RESULTS: Thirteen of the 15 patients experienced mild esophagitis. The average
      relative expansion increased as the treatment progressed. For all patients the
      esophagus was thicker at the final week of treatment than its pre-treatment size.
      For 7/15 patients the esophageal expansion was larger than 1.3. The average
      relative expansion of the esophagus was 1.30+/-0.19 (range: 1.04 - 1.67). We will
      present dose-response curves calculated from the weekly 4DCTs. CONCLUSIONS: The
      esophagus expands in response to radiation, reaching approximately a 30% increase
      in cross-sectional area during the final week of a 50.4Gy treatment, although
      there is much variability between patients.

PMID- 28517342
TI  - SU-E-T-220: A Web-Based Research System for Outcome Analysis of NSCLC Treated
      with SABR.
AB  - PURPOSE: To establish a web-based software system, an electronic patient record
      (ePR), to consolidate and evaluate clinical data, dose delivery and treatment
      outcomes for non small cell lung cancer (NSCLC) patients treated with
      hypofractionated stereotactic ablative radiation therapy (SABR) across
      institutions. METHODS: The new trend of information technology in medical imaging
      and informatics is towards the development of an electronic patient record (ePR),
      in which all health and medical information of each patient are organized under
      the patient's name and identification number. The system has been developed using
      the Wamp Server, a package of Apache web server, PHP and MySQL database to
      facilitate patient data input and management, and evaluation of patient clinical
      data and dose delivery across institution using web technology. The data of each
      patient to be recorded in the database include pre-treatment clinical data,
      treatment plan in DICOM-RT format and follow-up data. The pre-treatment data
      include demographics data, pathology condition, cancer staging. The follow-up
      data include the survival status, local tumor control condition and toxicity. The
      clinical data are entered to the system through the web page while the treatment
      plan data will be imported from the treatment planning system (TPS) using DICOM
      communication. RESULTS: The collection of data of NSCLC patients treated with
      SABR stored in the ePR is always accessible and can be retrieved and processed in
      the future. The core of the ePR is the database which integrates all patient data
      in one location. CONCLUSIONS: The web-based DICOM RT ePR system utilizes the
      current state-of-the-art medical informatics approach to investigate the
      combination and consolidation of patient data and outcome results. This will
      allow clinically-driven data mining for dose distributions and resulting
      treatment outcome in connection with biological modeling of the treatment
      parameters to quantify the efficacy of SABR in treating NSCLC patients.

PMID- 28517343
TI  - SU-E-T-260: Radiation Exposure Estimation for 131Cs Prostate Implant Patient
      Release Determination.
AB  - PURPOSE: Due to the short half-life and high energy of Cesium-131 (131Cs), the
      exposure rate outside the patient could potentially increase radiation exposure
      to hospital staff and exceed the maximum patient release exposure rate limit. A
      calculation technique has been developed to estimate the exposure rate at 1 meter
      from the patient, for prostate patients receiving 131Cs implants. METHODS: In our
      calculation for each patient, all 131Cs sources were treated as one single
      source, and the point on the prostate with the shortest distance to skin surface
      was selected as the effective source position. Attenuation inside the patient was
      calculated based on the attenuation coefficient of 30 keV photons in water,
      assuming homogeneous patient density. This calculation technique was evaluated on
      our first 25 131Cs implant patients. For comparison, the exposure rate at
      approximately 1 meter inferior to patient perineum was measured prior to patient
      release using the Inovision 451P-RYR survey meter. RESULTS: The distance from the
      edge of the prostate to skin surface along the inferior direction was the
      shortest in all 25 patients. The mean of the calculated exposure rates at 1 meter
      from skin surface was 0.53 mR/hr, 0.53 mR/hr, 0.04 mR/hr, 0.04 mR/hr and 1.5
      mR/hr along the anterior, posterior, left, right and inferior directions,
      respectively. The mean of the measured exposure rate at 1 meter inferior to
      patient perineum was 1.1 mR/hr. The mean ratio of the measured versus calculated
      exposure rate was 0.74 (standard deviation = 0.23). CONCLUSIONS: Our calculation
      technique is useful in determining in advance whether a patient may require
      hospitalization after his implant. The exposure rate at 1 meter inferior to
      patient perineum is a good indicator for determining whether the exposure rate
      along any direction might exceed the maximum allowed patient release exposure
      rate of 6 mR/hr.

PMID- 28517344
TI  - SU-E-T-230: Field Factor Verification in Small Fields.
AB  - PURPOSE: Small field is being commonly used in radiosurgery and IMRT, however
      dosimetry is challenging due to source size, electronic disequilibrium and
      detector size. Correction factor, K, has been published for a limited set of
      detectors and beam energies. Validity of K for several detectors is investigated.
      Also extrapolation ion chamber could be used using reciprocity theorem for small
      fields which is attempted in this study. METHODS: Various small volume detectors:
      IBA SFD, PTW TN60012 diode, and PTW Pinpoint N31006, Standard Imaging A16, along
      with Nuclear Associate N2339IT extrapolation chamber were used to measure output
      of square fields from 1*1 to 10*10 cm2 for Varian 6 and 16 MV beams. Measurements
      were made in a water phantom at 1.5cm depth for 6MV photon and 3.0cm depth for
      15MV photon with SSD 100cm. Extrapolation chamber was used in solid water.
      Published correction factors (Francescon et al, MP, 2011)1, K were used for the
      detectors used in this study. The K value was derived for extrapolation chamber
      by modeling based on the difference between its detector output and the average
      output factor from the diodes and pinpoints. RESULTS: The variation in output as
      measured from different detector is significant (+/-7.0%) for field sizes = 3*3
      cm2 and converges after large field sizes for both energies. The output factor
      for the extrapolation chamber was out of range from diodes/pinpoints in both 6MV
      and 16 MV beams. After applying detector K, the field size factors agree each
      other within +/-2.2% for all field sizes. CONCLUSIONS: The value of K provides
      reasonably good data for field factors irrespective of detector and the field
      factors can be matched within 2.2%. A mathematical function for extrapolation
      chamber also provides field factors comparable to the other detectors.

PMID- 28517345
TI  - SU-E-T-245: Survival Fractions for Head-And-Neck Cancer Derived from Tumor-Volume
      Variation Curves Using a 2-Level Cell Population Model.
AB  - PURPOSE: Volumetric tumor response to radiotherapy is an integrated process which
      includes several radiobiological mechanisms, such as cell killing, cell
      proliferation, dead-cell removal and tumor reoxygenation. Our goal is to
      reconstruct the information about these underlying radiobiological processes and
      specifically the cell survival fractions by fitting a 2-level cell-population
      tumor-volume model to imaging-derived tumor-volume variation curves obtained
      during radiotherapy for head-and-neck cancer. METHODS: Modeling tumor-volume
      during radiotherapy is a challenging problem because it is described by a sum of
      exponentials; therefore, the problem of accurately fitting a model to measured
      data is ill-posed. As an initial point of this research, we utilize a simplest 2
      level cell-population tumor-volume model which separates the entire tumor-cell
      population into oxygenated viable cells and oxygenated lethally damaged cells.
      The 2-level cell population tumor model has the advantage of being conditionally
      well-posed. We integrated this parameterized radiobiological model with a least
      squares objective function and a simulated annealing optimization algorithm to
      characterize individual patients' time-dependent tumor-volume regression rates.
      The measured tumor-volume variation curves were taken from a clinical study on
      tumor-volume variation during radiotherapy for 14 head-and-neck cancer patients
      in which an integrated CT/linac system was used for tumor-volume measurements.
      RESULTS: The 2-level tumor volume modeling is able to predict tumor behavior
      throughout an entire treatment for 8 of 14 patients. The average survival
      fraction 0.44 agrees very well with the published survival fraction of 0.45 for
      the head-and-neck squamous cell carcinoma. However, the 2-level model cannot
      describe the variation of the cell disintegration rate which is observed at the
      end of treatment for some of the head-and-neck cancer patients. CONCLUSIONS: The
      2-level cell population model is an acceptable approximation for the tumor-volume
      for some clinical cases, but it cannot describe all tumor-volume regression
      cases. This may be explained by omitting hypoxia in the 2-level model.

PMID- 28517346
TI  - SU-E-T-214: Predicting Plan Quality from Patient Geometry: Feature Selection and
      Inference Modeling.
AB  - PURPOSE: To investigate and develop methods to infer treatment plan quality from
      the geometric features of PTV/OAR structures; to discover and identify features
      of high prognostic values. METHODS: This study explores the prognostic utility of
      geometric features of two categories: (1) absolute geometry, characterizing the
      volumes of single structures (PTV, OARs); and (2) relative geometry, based on the
      minimal 3D distance and/or overlapping volume between pairs of structures. Using
      prostate as a pilot site, we developed inference models to 'predict' SBRT plan
      quality of DVH end points. We developed and assessed (1) a full linear regression
      model based on both absolute and relative geometric features, (2) a sparsity
      penalized linear regression model, (3) a linear regression model based on
      absolute geometry features only; (4) a learning-based nonparametric model. Cross
      validation was used for both selecting the parameter values as well as
      quantifying the inference performance. The best inference method for each of the
      DVH end points was identified to reveal the structural and prognostic differences
      among them. RESULTS: For linear regression, using sparsity-regularization
      discovered geometric features that were mostly absolute, demonstrating their
      dominant linear prognostic utility. However, introducing relative geometric
      features improved the plan quality prediction by 15% for all DVH end points. In
      contrast, nonparametric models had a heavier dependence on relative geometry
      features. While linear regression based on both features sets predicted OAR DVH
      points slightly better, the nonparametric method excelled in predicting PTV
      coverage and conformality. CONCLUSIONS: The inference result from this study
      provides an 'expectation' for the plan quality before the planning is to be
      performed, providing reference goals for the planner and a baseline for detecting
      abnormality. The use of relative geometry complements the absolute geometry with
      information on spatial configuration of the PTV/OAR structures of individual
      patients, and the variation in achievable conformality as a consequence.

PMID- 28517347
TI  - SU-E-T-223: High-Energy Photon Standard Dosimetry Data: A Quality Assurance Tool.
AB  - PURPOSE: Describe the Radiological Physics Center's (RPC) extensive standard
      dosimetry data set determined from on-site audits measurements. METHOD AND
      MATERIALS: Measurements were made during on-site audits to institutions
      participating in NCI funded cooperative clinical trials for 44 years using a
      0.6cc cylindrical ionization chamber placed within the RPC's water tank.
      Measurements were made on Varian, Siemens, and Elekta/Philips accelerators for 11
      different energies from 68 models of accelerators. We have measured percent depth
      dose, output factors, and off-axis factors for 123 different accelerator
      model/energy combinations for which we have 5 or more sets of measurements. The
      RPC analyzed these data and determined the 'standard data' for each model/energy
      combination. The RPC defines 'standard data' as the mean value of 5 or more sets
      of dosimetry data or agreement with published depth dose data (within 2%).
      RESULTS: The analysis of these standard data indicates that for modern
      accelerator models, the dosimetry data for a particular model/energy are within
      i,+/-2%. The RPC has always found accelerators of the same make/model/energy
      combination have the same dosimetric properties in terms of depth dose, field
      size dependence and off-axis factors. Because of this consistency, the RPC can
      assign standard data for percent depth dose, average output factors and off-axis
      factors for a given combination of energy and accelerator make and model.
      CONCLUSIONS: The RPC standard data can be used as a redundant quality assurance
      tool to assist Medical Physicists to have confidence in their clinical data to
      within 2%. The next step is for the RPC to provide a way for institutions to
      submit data to the RPC to determine if their data agrees with the standard data
      as a redundant check. This work was supported by PHS grants CA10953 awarded by
      NCI, DHHS.

PMID- 28517349
TI  - SU-E-T-207: Flatness and Symmetry Threshold Detection Using Statistical Process
      Control.
AB  - PURPOSE: AAPM TG-142 guidelines state that beam uniformity (flatness and
      symmetry) should maintain a constancy of 1 % relative to baseline. The focus of
      this study is to determine if statistical process control (SPC) methodology using
      process control charts (PCC) of steering coil currents (SCC) can detect changes
      in beam uniformity prior to exceeding the 1% constancy criteria. METHODS: SCCs
      for the transverse and radial planes are adjusted such that a reproducibly useful
      photon or electron beam is available. Transverse and radial - positioning and
      angle SCC are routinely documented in the Morning Check file during daily warm
      up. The 6 MV beam values for our linac were analyzed using average and range
      (Xbar/R) PCC. Using this data as a baseline, an experiment was performed in which
      each SCC was changed from its mean value (steps of 0.01 or 0.02 Ampere) while
      holding the other SCC constant. The effect on beam uniformity was measured using
      a beam scanning system. These experimental SCC values were plotted in the PCC to
      determine if they would exceed the predetermined limits. RESULTS: The change in
      SCC required to exceed the 1% constancy criteria was detected by the PCC for 3
      out of the 4 steering coils. The reliability of the result in the one coil not
      detected (transverse position coil) is questionable because the SCC slowly
      drifted during the experiment (0.05 A) regardless of the servo control setting.
      CONCLUSIONS: X-bar/R charts of SCC can detect exceptional variation prior to
      exceeding the beam uniformity criteria set forth in AAPM TG-142. The high level
      of PCC sensitivity to change may result in an alarm when in fact minimal change
      in beam uniformity has occurred. Further study is needed to determine if a
      combination of individual SCC alarms would reduce the false positive rate for
      beam uniformity intervention. This project was supoorted by a grant from Varian
      Medical Systems, Inc.

PMID- 28517348
TI  - SU-E-T-234: LET Measurement Using Nuclear Emulsion and Monte Carlo Simulation for
      Proton Beam.
AB  - PURPOSE: The significant issue of particle therapy such as proton and carbon ion
      biological effect on tumors and normal tissue. This effect closely connected with
      linear-energy-transfer (LET). This work presents a Monte Carlo study using GEANT4
      and the verification using Nuclear Emulsion to show LET for proton beam. METHODS:
      National Cancer Center (NCC) has IBA Beam Nozzle and cyclotron for proton
      therapy. We use proton beam bragg peak range 14cm. Also, we already developed the
      simulation using GEANT4 and finished validation for scattering proton beam. In
      our simulation, we make same condition with experimental setup.Nuclear emulsion
      films interleaved with tissue equivalent absorbers can be fruitfully used to
      reconstruct proton tracks with very high precision. This Nuclear emulsion film
      has been supported from Nagoya University, analyzed in Pusan University, was
      irradiated with a therapeutic proton beam at NCC. The Emulsion packs was located
      at entrance and bragg peak region of proton. This position means low and high LET
      region. The scanning of the emulsions has been performed at Nagoya University,
      where a fully automated microscopic scanning technology has been developed for
      the OPERA experiment on neutrino oscillations. RESULTS: We could see the
      reconstructed track of proton scanning emulsion. From film scanning, we got the
      LET distribution at low and high LET region for several proton tracks. Simulation
      results was similar distribution within standard deviation in acceptance level.
      Also we got the RBE distribution using LET measurement for proton beam.
      CONCLUSIONS: We measured LET at entrance and bragg peak region using Monte Carlo
      study and Nuclear Emulsion film, for NCC proton beam. This results means the good
      observation of LET using the nuclear emulsion. And this method can be used
      successfully in medical field.

PMID- 28517350
TI  - SU-E-T-217: Automated Data Mining of Lung SBRT Cases for Predicting Dosimetric
      Indices in Prospective Plans.
AB  - PURPOSE: To develop an automated technique for evaluating lung stereotactic body
      radiotherapy (SBRT) plan quality and predicting achievable lung dose constraints.
      METHODS: We examined the workflow scripting capabilities of a radiation oncology
      software package (MIM Software Inc) for automatically generating mean dose
      gradients and overlap volume histograms (OVHs) for lung SBRT plans. Mean dose
      gradients were created to assess plan quality by quantifying the dose fall-off
      from the planning target volume (PTV) into the ipsilateral lung. OVHs were
      created to evaluate potential predictors of achievable lung dose constraints by
      measuring the amount of ipsilateral lung volume overlapping the uniformly
      expanded PTV. Based on the knowledge that OVHs will depend on the size and
      spatial relationship of the lung and PTV structures, we hypothesize that OVH
      derived indices will therefore serve as predictors of achievable lung dose. The
      workflow scripts were evaluated in a pilot study of 10 lung SBRT plans (50 Gy in
      5 fractions) with varying PTV sizes and locations. RESULTS: The scripted
      workflows were successful in automatically generating mean dose gradients and
      OVHs for the PTV and ipsilateral lung. The workflows were able to produce the
      aforementioned data in a matter of seconds (per patient), which would have
      otherwise been excessively time consuming and labor intensive. From the pilot
      study, the average mean dose gradient was - 4.1 +/- 0.6, indicating that all
      evaluated patients had similar and acceptable plan quality. Furthermore, the OVH
      data indicated that a 0 mm PTV expansion and a 10 mm PTV expansion correlated
      with the mean lung dose (correlation coefficients of 0.71 and 0.56,
      respectively). CONCLUSIONS: Our current data demonstrate that mean lung dose
      correlates to multiple OVH indices. These results indicate that automated large
      scale mining of retrospective data is a highly promising approach for predicting
      dosimetric indices in prospective lung SBRT plans.

PMID- 28517351
TI  - SU-E-T-246: Preliminary Normal Tissue Complication Probability (NTCP) Analysis
      for Radiation Pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT).
AB  - PURPOSE: NTCP analysis was performed with Lyman model to study the dose tolerance
      limits for radiation-induced pneumonitis (RP) in hypofractionated SBRT. Since
      SBRT is increasingly being applied for the treatment of large and central tumors,
      it is important from a clinical point of view to determine the dose tolerance
      limits for specific risk of toxicity. METHODS: Eighteen consecutive patients who
      were treated using volumetric modulated arc therapy (RapidArc) for lung tumors
      exceeding 80cc were assessed. The evaluation of toxicity was scored using Common
      Toxicity Criteria AE4.0. Median follow-up time was 12.8 months. Clinical outcomes
      have been published, and we performed an NTCP analysis to determine the
      complication rate in relation to statistical dose tolerance limits. The dose
      volume histogram (DVH) reduction techniques of the total lung V20Gy, V15Gy,
      V10Gy, V5Gy and mean lung dose (MLD) were each analyzed, as well as the
      ipsilateral lung V5Gy and the contralateral lung V5Gy. The framework of the Lyman
      Model was used except that each DVH reduction method was analyzed independently
      instead of using the power-law relationship for volume dependence. Model
      parameters were fitted using the Maximum Likelihood technique. RESULTS: RP was
      reported in 5 patients (CTC Grade 2 in 3, and Grade 3 in 2). Total lung V5Gy and
      contralateral lung V5Gy were the best predictors of RP (p < 0.0001 for both). For
      V5Gy, the 10% risk level for Grade 2-3 RP was 28.4% for total lung and 21.6% for
      contralateral lung. CONCLUSIONS: Analysis of RP endpoints has identified total
      lung V5Gy and contralateral lung V5Gy as the best predictors of RP following
      RapidArc. These findings are based on limited clinical data, and longer follow-up
      in larger patient cohorts is required in order to determine more accurate dose
      tolerance limits. Dr. Grimm developed the DVH Evaluator, described at
      www.DiversiLabs.com and distributed by www.LifeLineSoftware.com. The analysis
      presented here is part of that software. Dr. Senan's department has received
      research funding from Varian Medical Systems, and Dr. Senan has received speakers
      honoraria from Varian.

PMID- 28517352
TI  - SU-E-T-255: A Novel Rectal Obturator for Prostate Radiotherapy Improves the
      Spatial Distribution of Dose and Reduces the Predicted Risk for Rectal Bleeding
      and Subjective Sphincter Control.
AB  - PURPOSE: To investigate the effects of an endorectal device during prostate
      radiotherapy on the spatial distribution of dose to the ano-rectal region and
      quantify implications for normal-tissue-complication probabilities. METHODS:
      Twenty-three patients with localised prostate cancer, referred for external beam
      radiotherapy had 2 CT scans acquired, without and with the rectal obturator
      (ProSpare) in-situ. For each patient two dose distributions were generated, based
      on both CT scans. Dose-surface maps for the rectal surface and the anal surface
      were generated and mean dose as well as a spatial measure (circumference of the
      dose distribution) were determined for all patients, with and without ProSpare.
      Using previously published NTCP models, the effect of ProSpare on NTCP was
      investigated for rectal bleeding and subjective sphincter control. RESULTS: In a
      previous study subjective sphincter control correlated strongest with mean dose
      and lateral extent at 53 Gy. The use of ProSpare resulted in a highly significant
      reduction of the lateral extent at 53 Gy (p=0.006), mean dose (p=0.0009) and NTCP
      according to the LKB model (p=0.002 for grade 2 and p=0.001 for grade >=1). In a
      previous study we reported that rectal bleeding correlated most strongly with the
      lateral extent at 55 Gy and presented the constraint that it should not exceed
      42% of the circumference. Using ProSpare resulted in a significant reduction of
      the lateral extent at 55 Gy (p=0.001) and significantly more patients met that
      proposed constraint (p=0.047). ProSpare resulted in a significant reduction of
      NTCP for grade-2 rectal bleeding (p=0.007) and a reduction for rectal bleeding
      grade >=1 (p=0.053). CONCLUSIONS: ProSpare resulted in a significant reduction of
      mean dose to the anal sphincter and a significant reduction of the lateral extent
      at 55 Gy. This corresponded to a significant reduction in the predicted risk of
      reporting subjective sphincter control and grade-2 rectal bleeding.

PMID- 28517354
TI  - SU-E-T-209: Four-Dimensional Gamma Method for Dose-Guided Radiotherapy.
AB  - PURPOSE: The technique known as 'Gamma Evaluation Method' was an effective
      measure for dose distribution comparison; however, it could not be used for
      accurate real-time verification because of the unstable systematic factors. To
      reduce the errors induced by systematic factors and there was a requirement for
      real-time dose verification in Dose-guided Radiotherapy (DGRT), the formula of
      Gamma Method was improved, and four-dimensional(4D) Gamma Method was proposed.
      METHODS: The gamma index, showing the deviation of two sets of dose
      distributions, should remove the error caused by different treatment delivery
      time to realize accurate real-time verification in Dose-guided Radiotherapy.
      Besides dose and distance, the variable of time, which was proportional to
      monitor unit (MU), was added to the formula. The criterion for acceptable
      distribution was generally defined as a tolerance of the dose, the distance and
      monitor unit. The algorithm was designed and realized using the tool of Microsoft
      Visual C++ 6.0. RESULTS: Two typical five beam treatment plans of Conformal
      Radiotherapy and Intensity-Modulated Radiotherapy were adopted to verify the
      algorithm. The two-dimensional (2D) ionization chamber MatriXX was used to
      measure the dose distribution. The verification for each beam was as follows: (1)
      analyze the evaluation results of gamma method and the improved gamma method.
      (2)Analyze the evaluation results of measured dose distributions at different
      time with the same dosage .The result showed that there existed errors caused by
      systematic factors before formula was improved. Improved method could obviously
      reduce the error induced by systematic factors, meeting DGRT's requirement for
      accurate real-time verification. The result could also be used to judge the
      stability of the accelerator. CONCLUSIONS: The 4-dimensional gamma method could
      reduce errors caused by systematic factors, and it could be used to reflect the
      stability of different accelerators. Supported by the National Natural Science
      Foundation under grant No.30900386 and the National Science Foundation of Anhui
      Province (Nos.090413095 and111040606Q55).

PMID- 28517353
TI  - SU-E-T-240: Accuracy of Dose Attenuation Correction for a 6D Carbon Fiber
      Treatment Couch Using a Virtual Couch Technique Integrated into a Treatment
      Planning System.
AB  - PURPOSE: A commercial 6D carbon fiber radiotherapy treatment couch (Imaging Couch
      Top, BrainLAB) has recently been reported to attenuate photon beams and increase
      skin dose. To prevent skin toxicity and ensure the target dose, it is important
      to correct the attenuation properties of the treatment couch with the treatment
      planning system (TPS). In this study, we evaluated the accuracy of dose
      attenuation correction by a virtual couch technique integrated into the TPS.
      METHODS: A virtual couch was modeled in the TPS (Eclipse v10.0, Varian). The CT
      value of the virtual couch was assigned with the CT value of the kilovoltage-CT
      images of the treatment couch. A phantom consisting of several plastic water
      slabs was created. We selected an evaluation point within the phantom on the
      couch structure at a 9 cm depth from the couch surface, which was placed at the
      isocenter. The doses at this point were calculated and measured at several gantry
      angles, from 120 degree to 240 degree at 10 degree steps, and each field size was
      10 cm * 10 cm. The prescribed dose was 100 monitor units for 6/10 MV photon beams
      and 6 MV-SRS mode (Trilogy Tx, Varian). Dose measurements were performed with an
      ion chamber. RESULTS: The largest difference between measured and calculated
      doses was 3.3% for a gantry angle of 120 degree and 6 MV-SRS mode. The average
      dose difference was within 1.6% for all gantry angles and photon beams. In the
      case without attenuation correction, the largest difference was 8.2% and the
      average difference was 5.2%. CONCLUSIONS: Use of the virtual couch technique in
      TPS accomplished sufficient accuracy for dose attenuation correction of the 6D
      carbon fiber treatment couch, and it is an effective method for clinical use.

PMID- 28517355
TI  - SU-E-T-249: Theoretical Analysis of the Effects Uncertainties Have On Treatment
      Outcomes.
AB  - PURPOSE: Mathematical models are used in Industrial & Systems Engineering to
      analyze complex integrated operational systems. Adapting this approach to
      radiation therapy can help quantify the precision and accuracy necessary to
      achieve optimal outcome of radiation treatment. The purpose of this work is to
      develop such a model using clinical data and assess the effect uncertainties have
      on treatment outcomes. METHODS: The Taguchi Loss Function (TLF) is adapted to
      radiation therapy using conventional radiobiological models for tumor control
      probabilities (TCP) and normal tissues complication probabilities (NTCP) based on
      the equivalent uniform dose. The TCP and NTCP curves are combined to create a
      failure probability function for a given treatment plan. The composite effects of
      all uncertainties involved in treating a patient are modeled by a normal
      distribution. The standard deviation and mean of the normal distribution
      represent the precision and accuracy of a treatment. The failure probability
      function is convolved with the normal distribution to arrive at an expected
      failure probability. Precision was varied from 0.5% to 25% while accuracy ranged
      from +/-5% to investigate uncertainties effects on complication-free local tumor
      control. 3D 4-field box plans where compared to IMRT plans for 18 prostate
      patients using this method. RESULTS: The average expected failure probability at
      the prescription dose for the 3D 4-field box plans was 30.02% and 18.13% for the
      IMRT plans at zero uncertainty. At 25% uncertainty the expected failure
      probabilities were 76.85% and 64.36%, respectively. On average the IMRT plans
      failure probability was 14.84% less than the 3D 4-field box plans for all
      uncertainty levels. CONCLUSION: This study demonstrates that uncertainty in
      radiotherapy procedures has a quantifiable effect on treatment outcome. To
      further improve complication-free local tumor control we must both improve
      treatment technologies and improve quality to minimize the uncertainties in
      radiation therapy.

PMID- 28517356
TI  - SU-E-T-219: A Free and Open Source DICOM Solution: DicomPack.
AB  - PURPOSE: DicomPack aims to provide a Perl DICOM library to isolate DICOM
      complexity and facilitate creation of DICOM applications. METHODS: DicomPack was
      initially designed for research projects to process and exchange radiotherapy
      medical images and treatment plans among research institutions, as well as
      between treatment planning systems and Open Radiological Archiving and
      Communication System (ORACS) research database. DicomPack uses an extensible
      internal data structure to store any encoded information observing DICOM's
      tag/element structure. Therefore, DicomPack either populates a data structure by
      DICOM information or converts a populated data structure into DICOM format. In
      this way, DicomPack creates a DICOM file either from scratch or using an existing
      DICOM template upfront. And this design also enables DicomPack to handle nested
      sequence data and multi-frame images easily. Along with DicomPack?IO,
      DicomPack?Network provides a comprehensive solution of exchanging DICOM
      information through DIMSE (DICOM Message Service) protocol. Its callback plugin
      design provides a universal interface to all DIMSE commands (DIMSE-C and DIMSE
      N). Each time a new DIMSE command needs to be implemented, users only need to
      provide callback procedures to answer some basic questions, such as where to
      retrieve/store DICOM information. In addition, DicomPack provides examples, e.g.,
      DicomDumper, DicomAnonymizer, DicomStore, under DicomPack?Util to demonstrate how
      to develop DICOM applications through DicomPack. RESULTS: Conclusions: DicomPack
      is a pure Perl package, which means DicomPack only has dependency on core Perl
      functions. As free software, DicomPack can be redistributed and/or modified as
      Perl. The easiest way to install DicomPack is through cpan.org (Comprehensive
      Perl Archive Network). However, DicomPack is in no way intended to to interpret
      DICOM information and/or enforce DICOM conformance, which will be up to
      application developers.

PMID- 28517357
TI  - SU-E-T-259: A Statistical and Machine Learning-Based Tool for Modeling and
      Visualization of Radiotherapy Treatment Outcomes.
AB  - PURPOSE: Effective radiotherapy outcomes modeling could provide physicians with
      better understanding of the underlying disease mechanism, enabling to early
      predict outcomes and ultimately allowing for individualizing treatment for
      patients at high risk. This requires not only sophisticated statistical methods,
      but user-friendly visualization and data analysis tools. Unfortunately, few tools
      are available to support these requirements in radiotherapy community. METHODS:
      Our group has developed Matlab-based in-house software called DREES for
      statistical modeling of radiotherapy treatment outcomes. We have noticed that
      advanced machine learning techniques can be used as useful tools for analyzing
      and modeling the outcomes data. To this end, we have upgraded DREES such that it
      takes advantage of useful Statistics and Bioinformatics toolboxes in Matlab that
      provide robust statistical data modeling and analysis methods as well as user
      friendly visualization and graphical interface. RESULTS: Newly added key features
      include variable selection, discriminant analysis and decision tree for
      classification, and k-means and hierarchical clustering functions. Also, existing
      graphical tools and statistical methods in DREES were replaced with a library of
      the Matlab toolboxes. We analyzed several radiotherapy outcomes datasets with our
      tools and showed that these can be effectively used for building normal tissue
      complication probability (NTCP) and tumor control probability (TCP) models.
      CONCLUSIONS: We have developed an integrated software tool for modeling and
      visualization of radiotherapy outcomes data within the Matlab programming
      environment. It is our expectation that this tool could help physicians and
      scientists better understand the complex mechanism of disease and identify
      clinical and biological factors related to outcomes.

PMID- 28517358
TI  - SU-E-T-229: Monte Carlo Dosimetric Study of SAVI HDR Applicator for Partial
      Breast Irradiation.
AB  - PURPOSE: To investigate the dosimetric variation by Monte Carlo and
      experimentally simulating the situation with and without tissue invagination and
      the potential translation and rotation of the SAVI applicator for partial breast
      irradiation. METHODS: The SAVI applicator with the cavity filled with air and
      water was merged into a water phantom and the delivered dose was simulated by
      MCNP monte carlo program. The results verified using an ion chamber and film were
      compared with a homogenous dose calculation by the treatment planning system. A
      dose variation from the SAVI translational shift was simulated and measured by
      moving an ion chamber along with the central axis direction. A dose change from
      the SAVI rotation was simulated and measured by placing an ion chamber at a fixed
      point while rotating the SAVI device about the central axis. RESULTS: The
      dosimetric variations for the SAVI device were found to be related to the cavity
      dimension, source arrangement, and dwell times. For the single dwell source
      placed in the center of the applicator, the maximum difference of the dose with
      the air cavity at 1cm away from the air-water boundary is about 7% higher than
      that with water filling in the cavity. But the simulation and measurements with
      nearly fully loaded multi-sources for the same situation show a difference of
      less than 3%. The 3% dose variation in average was found from either the 3 mm
      translation or 3 degree rotation of the SAVI applicator. CONCLUSIONS: The maximum
      dosimetric effect of an air cavity is 7% off compared with a water filled cavity
      when a single dwell source position is used in the center of the central
      catheter. Multiple catheters of the SAVI applicator with a nearly fully loaded
      dwell source position produce the discrepancy of less than 3% and allow for
      optimal and conformal dose distribution to a lumpectomy cavity while minimizing
      the dose to adjacent normal structures.

PMID- 28517359
TI  - SU-E-T-244: High Spatial Resolution EBT2 Film Dosimetry.
AB  - PURPOSE: The purpose of this study was to measure depth dose curves and dose
      effects near high-Z interfaces with radiochromic EBT-2 films reaching a spatial
      resolution superior to conventional methods with no quality losses. METHODS: The
      setup is made of two 12cm stacks of RW3, fixing an EBT2 film in a vertical
      position. To measure a depth dose curve, the setup was irradiated with a 15MV
      photon beam (Siemens Primus). Since the film is positioned parallel to the beam
      propagation, the depth dose curve is measured with only one film per depth.
      Additionally, a dental gold alloy probe was inserted in the RW3 stack at 6cm
      depth and the dose enhancement in front of the probe was measured with the method
      described above. Hereby, the bottom edge of the film touches the probe's
      surface.The irradiated films were digitized with a resolution of 72dpi using an
      Epson 10000XL flatbed scanner with a transparency unit and alignment frames. With
      this setup, the spatial resolution is only limited by the scanning resolution.
      RESULTS: In order to verify the new measurement method, comparisons of the
      measured depth dose curves with the conventional method of placing the film
      orthogonal to the beam propagation showed deviations of lesser than 3%.The
      comparison of the dental gold measurements with Monte Carlo simulations shows a
      systematic lower measured dose which is still within 5% consistency. However
      attention has to be paid in the experimental setup and film preparation.
      CONCLUSIONS: The introduced method shows significant advantages to conventional
      orthogonal EBT2 film positioning. It shows a very high spatial resolution and the
      area of interest is only limited by the film size. The method will be used in
      further studies, to investigate dose profiles and dose effects near interfaces
      and in inhomogeneities.

PMID- 28517360
TI  - SU-E-T-213: Development of a Web Wrapper to Facilitate Radiotherapy Research.
AB  - PURPOSE: Researchers write many computer programs with unique implementations,
      usually requiring a great amount of effort for other researchers to learn how to
      install, configure, and use. Some programs require specialized hardware platforms
      such as GPU workstation or CPU cluster, which may not readily available for many
      researchers. This work develops a general web platform to 'wrap' radiotherapy
      software tools into a user friendly, browser-based interface. METHODS: We
      developed a web wrapper based on existing technologies (e.g. HTML5, JavaScript,
      PHP, Python, XML) to interface with command line-based research tools. This
      wrapper enables users to easily perform various tasks in any modern web browser,
      while underlying tools are launched remotely. Visitors can upload data, configure
      settings, process data remotely, then view, share, and download results with
      minimal effort. This web wrapper is developer friendly; new tools are easily
      integrated by editing XML configuration files. RESULTS: As a test case, we have
      successfully wrapped a set of command line tools, developed by our group, into a
      single web app, providing fluence map generation, CT image processing, and GPU
      based Monte Carlo (MC) dose calculation. The result is a web-based quality
      assurance tool. With this tool, users can upload compressed DICOM-RT files,
      recompute dose using the MC method, and evaluate the results by viewing dose
      distribution, 3D gamma index distribution and DVH curves. The entire work-flow
      can be completed within 2 minutes provided users have a reasonable Internet
      connection speed. CONCLUSIONS: We have developed an web wrapper to increase the
      accessibility of radiotherapy tools and reduce users' learning curve through a
      friendly web-based interface. This work also allows quick and easy deployment and
      distribution of software tools developed by researchers to the whole community.

PMID- 28517361
TI  - SU-E-T-222: How to Define and Manage Quality Metrics in Radiation Oncology.
AB  - PURPOSE: Since the 2001 IOM Report Crossing the Quality Chasm: A New Health
      System for the 21st Century, the need to provide quality metrics in health care
      has increased. Quality metrics have yet to be defined for the field of radiation
      oncology. This study represents one institutes initial efforts defining and
      measuring quality metrics using our electronic medical record and verify
      system(EMR) as a primary data collection tool. This effort began by selecting
      meaningful quality metrics rooted in the IOM definition of quality (safe, timely,
      efficient, effective, equitable and patient-centered care) that were also
      measurable targets based on current data input and workflow. METHODS: Elekta
      MOSAIQ 2.30.04D1 was used to generate reports on the number of Special Physics
      Consults(SPC) charged as a surrogate for treatment complexity, daily patient time
      in department(DTP) as a measure of efficiency and timeliness, and time from CT
      simulation to first LINAC appointment(STL). The number of IMRT QAs delivered in
      the department was also analyzed to assess complexity. RESULTS: Although initial
      MOSAIQ reports were easily generated, the data needed to be assessed and adjusted
      for outliers. Patients with delays outside of radiation oncology such as
      chemotherapy or surgery were excluded from STL data. We found an average STL of
      six days for all CT-simulated patients and an average DTP of 52 minutes total
      time, with 23 minutes in the LINAC vault. Annually, 7.3% of all patient require
      additional physics support indicated by SPC. CONCLUSIONS: Utilizing our EMR, an
      entire year's worth of useful data characterizing our clinical experience was
      analyzed in less than one day. Having baseline quality metrics is necessary to
      improve patient care. Future plans include dissecting this data into more
      specific categories such as IMRT DTP, workflow timing following CT-simulation,
      beam-on hours, chart review outcomes, and dosimetric quality indicators.

PMID- 28517362
TI  - The Absence of Quadrupolar Nuclei Facilitates Efficient 13 C Hyperpolarization
      via Reversible Exchange with Parahydrogen.
AB  - Nuclear spin hyperpolarization techniques are revolutionizing the field of 13 C
      molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is
      currently the leading technique, it is generally slow (requiring ~1 h) and costly
      (~$USD106 ). As a consequence of carbon's central place in biochemistry,
      tremendous progress using 13 C d-DNP bioimaging has been demonstrated to date
      including a number of clinical trials. Despite numerous attempts to develop
      alternatives to d-DNP, the competing methods have faced significant translational
      challenges. Efficient hyperpolarization of 15 N, 31 P, and other heteronuclei
      using signal amplification by reversible exchange (SABRE) has been reported in
      2015, but extension of this technique to 13 C has proven to be challenging. Here,
      we present efficient hyperpolarization of 13 C nuclei using micro-Tesla SABRE. Up
      to ca. 6700-fold enhancement of nuclear spin polarization at 8.45 T is achieved
      within seconds, corresponding to P13C ~4.4 % using 50 % parahydrogen (P13C >14 %
      would be feasible using more potent ~100 % parahydrogen). Importantly, the 13 C
      polarization achieved via SABRE strongly depends not only upon spin-lattice
      relaxation, but also upon the presence of 15 N (I=1/2) versus quadrupolar 14 N
      (I=1) spins in the site binding the hexacoordinate Ir atom of the catalytic
      complex. We show that different 13 C nuclei in the test molecular frameworks
      pyridine and acetonitrile-can be hyperpolarized, including 13 C sites up to five
      chemical bonds away from the exchangeable hydrides. The presented approach is
      highly scalable and can be applied to a rapidly growing number of biomolecules
      amendable to micro-Tesla SABRE.

PMID- 28517363
TI  - Cleave but not leave: Astrotactin proteins in development and disease.
AB  - Over the years, animal studies have identified astrotactins as important membrane
      proteins for glial-guided neuronal migration during central nervous system
      development and hair follicle polarity control during skin development.
      Biochemical studies have revealed intramembrane proteolysis as an important
      feature of astrotactins. The two fragments of astrotactins remain linked together
      by a disulfide bond after the proteolytic cleavage. In humans, mutations in
      astrotactin genes have also been linked to a wide range of diseases, including
      several developmental brain disorders, neurodegenerative diseases and cancer. In
      this review, I will summarize the current knowledge of the biological function of
      astrotactins in development, highlight the linkage between mutations in
      astrotactin genes and human disease and discuss several outstanding questions
      that remain unanswered. (c) 2017 IUBMB Life, 69(8):572-577, 2017.

PMID- 28517364
TI  - A cryptic pigment biosynthetic pathway uncovered by heterologous expression is
      essential for conidial development in Pestalotiopsis fici.
AB  - Spore pigmentation is very common in the fungal kingdom. The best studied pigment
      in fungi is melanin which coats the surface of single cell spores. What and how
      pigments function in a fungal species with multiple cell conidia is poorly
      understood. Here, we identified and deleted a polyketide synthase (PKS) gene
      PfmaE and showed that it is essential for multicellular conidial pigmentation and
      development in a plant endophytic fungus, Pestalotiopsis fici. To further
      characterize the melanin pathway, we utilized an advanced Aspergillus nidulans
      heterologous system for the expression of the PKS PfmaE and the Pfma gene
      cluster. By structural elucidation of the pathway metabolite scytalone in A.
      nidulans, we provided chemical evidence that the Pfma cluster synthesizes DHN
      melanin. Combining genetic deletion and combinatorial gene expression of Pfma
      cluster genes, we determined that the putative reductase PfmaG and the PKS are
      sufficient for the synthesis of scytalone. Feeding scytalone back to the P. fici
      DeltaPfmaE mutant restored pigmentation and multicellular adherence of the
      conidia. These results cement a growing understanding that pigments are essential
      not simply for protection of spores from biotic and abiotic stresses but also for
      spore structural development.

PMID- 28517365
TI  - Enantioselective dissipation of pyriproxyfen in soils and sand.
AB  - Under normal conditions, the environmental behaviors of pesticides are affected
      by complex environmental factors and the manner of administration together with
      constraints. In order to meet the actual needs, we imitated the experiment and
      found that the degradation rate of pyriproxyfen in soils rendered complex
      changes. Rac-pyriproxyfen was successfully chiral separated on an AZ-H column and
      the residue analysis method was in accord with the demand of pesticide analysis.
      The results indicated that pyriproxyfen dissipated at a faster rate in
      Heilongjiang soil and Hainan soil, while at a much slower speed in another three
      soils and sand. Obvious enantioselective degradation was observed in Hainan soil
      and Qingdao sand. The results suggested that pyriproxyfen alone had low
      persistence in soil, but the moisture, soil type, the use of mixture formulation,
      and second spraying treatment could play important roles in dissipation of
      pyriproxyfen. Too large and too small moisture content could both make
      pyriproxyfen persist for a longer period in soil than in soil with 25% moisture
      content. Residues dissipated much slower after using Ai Qiu, while Shi Dingkang
      did not have a big effect on degradation, with only a small acceleration effect.
      Pyriproxyfen also dissipated in Hainan soil with difficulty after the second
      treatment.

PMID- 28517366
TI  - Genie in a blotter: A comparative study of LSD and LSD analogues' effects and
      user profile.
AB  - OBJECTIVE: This study aimed to describe self-reported patterns of use and effects
      of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and
      the characteristics of those who use them. METHODS: An anonymous self-selected
      online survey of people who use drugs (Global Drug Survey 2016; N = 96,894),
      which measured perceived drug effects of LSD and its analogues. RESULTS: Most LSD
      analogue users (91%) had also tried LSD. The proportion of U.K. and U.S.
      respondents reporting LSD analogue use in the last 12 months was higher than for
      LSD only. LSD analogue users described the effects as psychedelic (93%), over
      half (55%) obtained it online, and almost all (99%) reported an oral route of
      administration. The modal duration (8 hr) and time to peak (2 hr) of LSD
      analogues were not significantly different from LSD. Ratings for pleasurable
      high, strength of effect, comedown, urge to use more drugs, value for money, and
      risk of harm following use were significantly lower for LSD analogues compared
      with LSD. CONCLUSIONS: LSD analogues were reported as similar in time to peak and
      duration as LSD but weaker in strength, pleasurable high, and comedown. Future
      studies should seek to replicate these findings with chemical confirmation and
      dose measurement.

PMID- 28517367
TI  - Rationale and design of a randomized trial to assess the safety and efficacy of
      MultiPoint Pacing (MPP) in cardiac resynchronization therapy: The MPP Trial.
AB  - BACKGROUND: Although the majority of Class III congestive heart failure (HF)
      patients treated with cardiac resynchronization therapy (CRT) show a clinical
      benefit, up to 40% of patients do not respond to CRT. This paper reports the
      design of the MultiPoint Pacing (MPP) trial, a prospective, randomized, double
      blind, controlled study to evaluate the safety and efficacy of CRT using MPP
      compared to standard biventricular (Bi-V) pacing. METHODS: A maximum of 506
      patients with a standard CRT-D indication will be enrolled at up to 50 US
      centers. All patients will be implanted with a CRT-D system (Quartet LV lead
      Model 1458Q with a Quadra CRT-D, Abbott) that can deliver both MPP and Bi-V
      pacing. Standard Bi-V pacing will be activated at implant. At 3 months
      postimplant, patients in whom the echocardiographic parameters during MPP are
      equal or better than during Bi-V pacing are randomized (1:1) to either an MPP or
      Bi-V arm. RESULTS: The primary safety endpoint is freedom from system-related
      complications at 9 months. Each patient's response to CRT will be evaluated using
      a heart-failure clinical composite score, consisting of a change in NYHA
      functional class, patient global assessment score, HF events, and cardiovascular
      death. The primary efficacy endpoint is the proportion of responders in the MPP
      arm compared with the Bi-V arm between 3 and 9 months. CONCLUSION: This trial
      seeks to evaluate whether MPP via a single quadripolar LV lead improves
      hemodynamic and clinical responses to CRT, both in clinical responders and
      nonresponders.

PMID- 28517368
TI  - Testicular thermoregulation, scrotal surface temperature patterns and semen
      quality of water buffalo bulls reared in a tropical climate.
AB  - This study evaluated the capacity of thermoregulation and its consequences on the
      scrotal surface temperature patterns and semen quality of buffalo bulls raised in
      a wet tropical climate. Eleven water buffaloes were evaluated in the rainiest, in
      the transitional and in the less rainy season. Air temperature and humidity were
      consistently high, but the animals did not show thermal stress in any season. The
      scrotal temperature gradient of buffalo bulls using infrared thermography was
      described, and three parallel and decreasing thermal bands were characterised.
      Sperm quality (n = 176 ejaculates) was maintained in normal parameters over the
      periods. Pearson's coefficients showed that sperm volume and progressive motility
      were negatively correlated with ocular globe, epididymal tail and minimum scrotal
      temperatures (p < .01). Sperm membrane integrity was negatively influenced by
      increases in epididymal tail and minimum scrotal temperatures (p < .01). Ocular
      globe temperature also showed positive correlation with rectal, spermatic cord,
      and epididymal tail temperatures (p < .01). Therefore, even under high
      temperature and humidity, the thermoregulatory system was effective in preventing
      heat stress and the normality of scrotal surface temperatures, spermatogenesis
      and sperm maturation were maintained.

PMID- 28517369
TI  - Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A
      systematic review.
AB  - BACKGROUND: Primary biliary cholangitis (PBC), formerly known as primary biliary
      cirrhosis, is a chronic cholestatic liver disease characterized by an immune
      mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has
      been the primary medication for the treatment of PBC, resulting in improved liver
      tests, resolution of symptoms and increased transplant free survival. However,
      not all patients respond to UDCA. The aim of this systematic review is to provide
      an evidence based assessment of the medications that have been studied in
      patients who are refractory to UDCA. METHODS: We performed a systematic
      literature search on MEDLINE and the Cochrane Database of Systematic Reviews of
      the published literature. A total of 23 articles fulfilling our inclusion
      criteria were found. RESULTS: Several studies have shown an improvement in liver
      biochemistries with the use of obeticholic acid in conjunction with UDCA.
      Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit
      in this population but need more robust studies to confirm these observational
      results. Neither obeticholic acid nor fibrates have shown to increase transplant
      free survival. While there may be some benefit with methotrexate, colchicine,
      budesonide, mycophenolate mofetil and azathioprine, these findings were not
      consistent and the benefits were marginal. Further investigation is needed.
      CONCLUSION: In patients with PBC refractory to UDCA, obeticholic acid or a
      fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further
      investigation with randomized controlled trials is needed to provide high quality
      evidence to formulate standardized therapies in this difficult to treat
      population.

PMID- 28517370
TI  - Evaluation of dietary methionine requirement of male Korean native ducks for 3
      weeks post-hatching.
AB  - A total of 336 1-day-old male Korean native ducks (KND) were used in a completely
      randomized design with seven dietary methionine levels (0.30-0.90% with 0.1%
      increment) to determine the methionine requirement of male Korean native ducks
      for 3 weeks after hatching. Each dietary treatment had six replicates with eight
      ducklings per pen. One duckling from each pen (n = 6) was sacrificed to weigh
      empty body and drumsticks at the end of the experiment. Final body weight and
      weight gain of 3 weeks old KND were increased with increasing dietary methionine
      levels up to 0.4%, and then decreased (P < 0.05) with a further increasing
      dietary methionine level. In contrast, feed conversion ratio of the KND decreased
      up to 0.4% and increased (P < 0.05) with the increasing dietary methionine level.
      Both empty body weight and proportions of empty body weight were linearly
      increased (P < 0.05) while the dietary methionine level elevated up to 0.4%.
      Estimated dietary methionine requirement for maximum body weights, daily gain and
      minimum feed conversion ratio were 0.36, 0.39 and 0.40%, respectively, when it
      was fitted into linear- and quadratic-plateau models.

PMID- 28517371
TI  - See one, do one, teach...a lifetime.

PMID- 28517372
TI  - Multicenter verification of the Sysmex XN-Series.
AB  - INTRODUCTION: Verification of hemocytometry equipment deviates significantly from
      that of clinical chemistry equipment due to the absence of appropriate control
      material and the need for fresh material. In practice, verification is limited to
      comparison with the previously used equipment and determination of
      reproducibilities. Particularly in multicenter settings, harmonization of results
      is necessary. If the same equipment is used in several laboratory departments,
      calibration and uniformity are important issues. METHODS: In this study, seven
      Sysmex XN hematology modules distributed over three laboratories were evaluated
      with the same set of samples (n=160). RESULTS: Results of each Sysmex XN
      hematology module were compared with the results of the Sysmex XE-2100 hematology
      analyzer using linear regression. Although excellent correlation coefficients
      were obtained, in many cases the criteria for slope and/or intercept were not
      met. Therefore, the same data were analyzed with Bland-Altman difference plots
      with three times the specified CV% of the parameter as limits of agreement. At
      least 90% of the determinations per parameter and per module must comply with
      those limits of agreement. Almost all parameters on each module fulfilled these
      criteria, and only RBC and Ht from respectively two and four XN modules had to be
      recalibrated. Reproducibility of each parameter was determined 10 times in
      patient samples with low, normal, and high levels. Reproducibility of all
      parameters was within the specifications of the manufacturer and the biological
      variability. CONCLUSION: With this straightforward method, all seven Sysmex XN
      hematology modules demonstrated uniform results, which were identical to those of
      the previously used Sysmex XE-2100 hematology analyzer, the performance of which
      was well known.

PMID- 28517374
TI  - SU-E-E-02: The Use of Social Media in a Medical Physics Classroom.
AB  - PURPOSE: The purpose of this presentation is to provide an example of how
      Facebook has been used in a medical physics classroom. METHODS: Facebook was used
      in an introductory course in radiation interactions taken by graduate students in
      a CAMPEP-accredited medical physics program. Facebook served two major functions
      in the class, as a means for communicating announcements to students, and as a
      forum for discussion of unclear points in the course. At the end of every class,
      students were prompted to fill out a questionnaire asking them to identify points
      that were not clear. After class, all questions were posted by the instructor (so
      students maintained anonymity and did not have to be embarrassed by lack of
      knowledge). Students had 24 hr to post responses to their peers' questions.
      Students who responded correctly to peers' questions received additional in-
      class credit for their response, thus encouraging them to respond. After 24 hr,
      the instructor or a teaching assistant posted a response to the question.
      RESULTS: 12/16 students participated in discussions. The students who did not
      respond were all postdoctoral fellows (3/4 foreign) auditing the course. From 3
      to 9 students typically responded to questions. Students responding to questions
      received credit for their responses (0.4 points per response up to a maximum of 5
      points added to an in-class grade that counted for 10% of their final grade).
      Student evaluations of the use of Facebook were generally positive. Furthermore,
      use of Facebook for this application extended the time students were interacting
      with each other in medical physics. CONCLUSIONS: The use of social media in a
      medical physics classroom appears to be an effective tool to incorporate into a
      teaching methodology.

PMID- 28517373
TI  - SU-D-217A-03: Nuclear Medicine Uniformity Assessment Using 2D Noise Power
      Spectrum.
AB  - PURPOSE: Nuclear medicine quality control programs require daily evaluation for
      the presence of potential non-uniformities by commonly utilizing a traditional
      pixel value-based assessment (Integral CFOVUniformity). While this method
      effectively captures regional non- uniformities in the image, it does not
      adequately reflect subtle periodic structures that are visually apparent and
      clinically unacceptable, therefore requiring the need for additional visual
      inspection of the image. The goal of this project was to develop a new uniformity
      assessment metric by targetingstructural patterns and more closely correlating
      with visual inspection. METHODS: The new quantitative uniformity assessment
      metric is based on the 2D Noise Power Spectrum (NPS). A full 2D NPS was performed
      on each image. The NPS was thresholded to remove quantum noise and further
      filtered by the visual response function. A score, the Structure Noise Index
      (SNI), was then applied to each based on the average magnitude of the structured
      noise in the processed image. To verify the validity of the new metric, 50 daily
      uniformity images with varying degrees of visual structured and non-structured
      non-uniformity were scored by 5 expert nuclear medicine physicists. The
      correlation between the visual score and SNI were assessed. The Integral CFOV was
      also compared against the visual score. RESULTS: Our new SNI assessment metric
      compared to the Integral CFOV showed in increase in sensitivity from 67% to 100%
      in correctly identifying structured non-uniformities. The overall positive
      predictive value also increased from 55% to 72%. CONCLUSIONS: Our new uniformity
      metric correlates much more closely with visual assessment of structured non-
      uniform NM images than the traditional pixel-based method. Using this new metric
      in conjunction with the traditional pixel value-based assessment will allow a
      more accurate quantitative assessment of nuclear medicineuniformity.

PMID- 28517375
TI  - SU-D-218-01: Support Vector Machine Tissue Classification of Multiparametric MRI
      Tumor Data.
AB  - PURPOSE: To test the accuracy of Support Vector Machines in the classification of
      Glioblastoma Multiforme tumor voxels usingmultiparametric MRI data. METHODS:
      Various MRI scans were collected from patients with recurrent GBM. Each scan
      session collected post-contrastT1(+C T1), T2, diffusion, perfusion, and multi
      echo hypoxia images. Thediffusion-weighted images were converted to Apparent
      Diffusion Coefficient (ADC) maps. The perfusion images were corrected for leakage
      and represented as corrected rCBV maps. All of these scans were co-registered to
      each other, giving an input matrix to our support vector machine consisting of
      roughly 13,000 voxels, each with 5 feature values (+C T1, T2, ADC, rCBVcorrected,
      delta T2*). The SVM was then trained usingradiologist confirmed labels for
      'cyst', 'tumor', and 'normal tissue'. These labels were obtained using
      longitudinal data as well as clinical scans, and tested on new data to determine
      the accuracy of classifying tumor and cyst voxels. RESULTS: The tumor model
      resulted in a specificity of 0.9841 and a sensitivity of 0.7498. The cyst model
      resulted in a specificity of 0.9825 anda sensitivity of 0.9414. Both models
      showed improvement with increasing features. CONCLUSIONS: These results show that
      the SVM is capable of classifying tumor and cyst voxels in a single case study.
      Aside from optimizing the current tumor model, future work will focus on the
      potential for the SVM to help in early detection of recurrence. In order to
      achieve this,we will need to test SVMs across patients. If we truly aim for early
      detection, then we need to prove that the algorithm can be trained on a pool of
      subjects with recurrent disease, and then test that model on a new patient before
      recurrence is obvious.

PMID- 28517376
TI  - SU-D-BRCD-04: Validation of Film Dosimetry in the Dose Build-Up Region.
AB  - PURPOSE: To establish a film dosimetric method for high-resolution measurement in
      the dose build-up region. METHODS: Percent depth dose (PDD) curves were measured
      in water for TomoTherapy using Gafchromic EBT2 films. Depth dose measurements
      were also performed using Standard Imaging A1SL and PTW PinPoint ionization
      chambers, as well as a PTW DiodeE detector. The film and detector measurements
      were then compared to Monte Carlo (MC) simulation data computed using PENELOPE.
      An in- house support apparatus was constructed to hold the films parallel to the
      beam central axis while being suspended in the water, simultaneously demarcating
      the water surface on the film. The films were converted to dose using a corrected
      net optical density method involving the red and blue color channels of an Epson
      Expression 10000XL scanner. Film analysis was performed using ImageJ software and
      MATLAB code developed in clinic. RESULTS: In our film method, a systematic shift
      of 1.2mm downstream is seen for the sample of five films, with good
      reproducibility within the sample (s=0.3mm). The film measurements showed a mean
      PDD difference of 0.3% (s=0.4%) with a maximum of 1.3% from that of MC between
      depths of 0.5mm to 20mm. The average film dose measured at the water surface
      (d=0mm) was 13.1% greater than that calculated by MC. EBT2 film shows much better
      agreement with MC in the dose build-up region than the ionization chamber and
      detector measurements. CONCLUSIONS: This study demonstrates the capability of
      EBT2 films for simple and accurate superficial dose measurements. A suspected
      reason for the systematic shift in film alignment is attributed to difficulty in
      determining water surface due to the meniscus that forms at the film. Funded by
      SSRMP Research Grant 2011.

PMID- 28517377
TI  - SU-D-BRA-03: Simultaneous MV-KV Imaging for Intra-Fractional Motion Management
      during Volume Modulated Arc Therapy (VMAT) Delivery on the Varian TrueBeam.
AB  - PURPOSE: To evaluate a MV-kV intra-fractional imaging technique for use during
      volume modulated arc therapy (VMAT) with the Varian TrueBeam. METHODS: MV-kV
      image pairs were acquired intra-fractionally during VMAT delivery. kV images (11
      fps) were acquired throughout delivery using a standard pre-programmed imaging
      template. MV images (9.5 fps) were acquired simultaneously by deploying the EPID
      and passively collecting the resulting images using Varian proprietary software,
      iTools Capture. Localization accuracy was evaluated by imaging a Rando phantom
      implanted with 3 fiducials while moving the couch according to XML- programmed
      trajectories simulating typical prostate and respiratory motion. VMAT delivery
      was done using a single 360 degree arc in TrueBeam Developer mode. The effect on
      accuracy of total MU and gantry speed was studied. To improve image quality, MV
      frame averaging was performed and the MV and kV images were then registered to
      their corresponding DRRs using in-house registration software. From these 2D
      registrations, the 3D position at each MV-kV acquisition point was determined.
      RESULTS: Between 130 and 390 MV-kV pairs were acquired for each delivery. The
      mean difference between planned couch and measured fiducial 3D positions with
      prostate motion was less than 0.03 cm in each direction (SD 0.03 cm). Neither
      gantry speed nor MU significantly impacted accuracy. for respiratory motion, the
      mean difference between planned and measured position was less than 0.04 cm.
      Standard deviation averaged 0.06 cm but increased to 0.12 cm with large
      instantaneous motion and less MV dose per frame. MV frame averaging and
      inaccuracies in MV image gantry angle determination also affected accuracy,
      particularly with significant motion. CONCLUSIONS: With high quality MV imaging,
      MV-kV localization techniques can be highly accurate, even in the presence of
      significant motion. As clinical MV-kV methods become available, such techniques
      can provide an efficient and accurate method for monitoring intra-fractional
      motion. This work was partially supported through a research agreement with
      Varian Medical Systems, Palo Alto, CA.

PMID- 28517378
TI  - SU-D-217BCD-01: Corrupted DICOM Image Recovering: A Clinical Experience.
AB  - PURPOSE: Colored DICOM secondary capture images generated from CT perfusion
      studies were corrupted if they were sent directly from a Siemens acquisition
      workstation to a GE viewing workstation. However, those images were properly
      displayed in the GE viewing workstation if they were transferred through a GE
      PACS first. The purpose of this work is to investigate the cause of image
      corruption and determine why passing through PACS corrected it. METHODS: DICOM
      headers of corrupted and non-corrupted (sent through the PACS) images were
      compared with a free DICOM software tool (http://DVTK.org); the differences were
      highlighted. Certain header tags were found in non-corrupted images, but not in
      corrupted images. These tags were sequentially removed until the non- corrupted
      image became corrupted. Once a candidate tag was found, fresh corrupt images were
      modified by adding a 'repair' tag and tested. RESULTS: It was found that the
      absence of Planar Configuration (0028, 0006) is the cause of image corruption.
      This attribute is used in the DICOM color image to specify whether the color
      pixel data are sent color-by-plane or color-by- pixel and should be present if
      the Sample per Pixel (0028, 0002) tag has a value greater than 1. In our DICOM
      color images, the values of (0028, 0002) and Photometric Interpretation (0028,
      0004) are 3 and RGB, respectively. Thus (0028, 0006) should equal 0 (color-by
      pixel), which is used for uncompressed or lossless compressed transfer syntaxes.
      Adding this tag and setting the value to zero manually repaired corrupt images.
      CONCLUSIONS: Using open source DICOM tools and following the described process
      can be a valuable ally in the search for causes of image corruption. Comparing
      the headers and finding the handful of different tags rapidly led to an
      explanation that could be used by the vendor for a permanent fix.

PMID- 28517379
TI  - SU-D-213AB-03: Design Optimization of a HDR Ir-192 Brachytherapy Skin Applicator
      Using Monte Carlo-Based Dosimetry.
AB  - PURPOSE: AccuBoost(r) applicators are designed to deliver boost dose after whole
      breast irradiation in substitution for electron boost. By augmenting the current
      design through adding a wedge inside the applicator and atungsten window above
      the skin surface, the AccuBoost applicators can be used to treat skin cancer.
      This study aimed to design a skin applicator that could deliver brachytherapy in
      a conformai and homogeneous manner to the skin while minimizing OAR dose.
      METHODS: The 6 cm round AccuBoost applicator served as the foundation for
      variations of an internal cone, internal wedge, and external window. Monte Carlo
      (MC) methods (MCNP5)were used for dose characterization and design optimization
      of these tungsten-alloy components. Specifically, the cone, wedge, and window
      dimensions were iteratively varied in MC simulations based on HDR Ir-192 dose
      distributions having (0.5 mm)2 voxels in a soft tissue phantom. The design goal
      was an applicator that can protect tissue > 5 mm while providing lateral dose
      conformity and a homogeneous dose distribution for tissue < 3 mm. RESULTS: The
      internal wedge angle governed field size to be irradiated, limiting depth-dose
      spread into the phantom. Dose conformity was enhanced by the internal cone and
      collimating window. Window thickness increased required treatment time, where 3
      mm was determined to be optimal when considering tradeoff between depth dose and
      dose rate. With a lesion thickness of 3 mm and setup uncertainty of 1 mm, the
      optimal design provided better lateral coverage at d = 5mm. Here, the dose was
      less than 30% of that within the treatment aperture. CONCLUSION: Standardized
      criteria were established for dose optimization of a skin applicator. Using these
      criteria and MC methods, an optimized design was obtained. Optimization is
      underway for other applicator diameters. Clinical evaluation within a 3D
      treatment planning system and comparison with other brachytherapy skin
      applicators is ongoing. Prof. Rivard is a stakeholder of Advanced Radiation
      Therapy, LLC.

PMID- 28517380
TI  - SU-D-218-05: Material Quantification in Spectral X-Ray Imaging: Optimization and
      Validation.
AB  - PURPOSE: To develop and validate a multivariate statistical method to optimize
      scanning parameters for material quantification in spectral x-rayimaging.
      METHODS: An optimization metric was constructed by extensively sampling the
      thickness space for the expected number of counts for m (two or three) materials.
      This resulted in an m-dimensional confidence region ofmaterial quantities, e.g.
      thicknesses. Minimization of the ellipsoidal confidence region leads to the
      optimization of energy bins. For the given spectrum, the minimum counts required
      for effective material separation can be determined by predicting the signal-to
      noise ratio (SNR) of the quantification. A Monte Carlo (MC) simulation framework
      using BEAM was developed to validate the metric. Projection data of the m
      materials was generated and material decomposition was performed for combinations
      of iodine, calcium and water by minimizing the z-score between the expected
      spectrum and binned measurements. The mean square error (MSE) and variance were
      calculated to measure the accuracy and precision of this approach, respectively.
      The minimum MSE corresponds to the optimal energy bins in the BEAM simulations.
      In the optimization metric, this is equivalent to the smallest confidence region.
      The SNR of the simulated images was also compared to the predictions from the
      metric. RESULTS: TheMSE was dominated by the variance for the given material
      combinations,which demonstrates accurate material quantifications. The
      BEAMsimulations revealed that the optimization of energy bins was accurate to
      within 1keV. The SNRs predicted by the optimization metric yielded satisfactory
      agreement but were expectedly higher for the BEAM simulations due to the
      inclusion of scattered radiation. CONCLUSIONS: The validation showed that the
      multivariate statistical method provides accurate material quantification,
      correct location of optimal energy bins and adequateprediction of image SNR. The
      BEAM code system is suitable for generating spectral x- ray imaging simulations.

PMID- 28517381
TI  - SU-D-BRB-02: Investigations of Secondary Ion Distributions in Carbon Ion Therapy
      Using the Timepix Detector.
AB  - PURPOSE: Due to the high conformity of carbon ion therapy, unpredictable changes
      in the patient's geometry or deviations from the planned beam properties can
      result in changes of the dose distribution. PET has been used successfully to
      monitor the actual dose distribution in the patient. However, it suffers from
      biological washout processes and low detection efficiency. The purpose of this
      contribution is to investigate the potential of beam monitoring by detection of
      prompt secondary ions emerging from a homogeneous phantom, simulating a patient's
      head. METHODS: Measurements were performed at the Heidelberg Ion-Beam Therapy
      Center (Germany) using a carbon ion pencil beam irradiated on a cylindrical PMMA
      phantom (16cm diameter). For registration of the secondary ions, the Timepix
      detector was used. This pixelated silicon detector allows position-resolved
      measurements of individual ions (256*256 pixels, 55MUm pitch). To track the
      secondary ions we used several parallel detectors (3D voxel detector). RESULTS:
      For monitoring of the beam in the phantom, we analyzed the directional
      distribution of the registered ions. This distribution shows a clear dependence
      on the initial beam energy, width and position. Detectable were range differences
      of 1.7mm, as well as vertical and horizontal shifts of the beam position by 1mm.
      To estimate the clinical potential of this method, we measured the yield of
      secondary ions emerging from the phantom for a beam energy of 226MeV/u. The
      differential distribution of secondary ions as a function of the angle from the
      beam axis for angles between 0 and 90 degrees  will be presented. In this setup
      the total yield in the forward hemisphere was found to be in the order of 10-1
      secondary ions per primary carbon ion. CONCLUSIONS: The presented measurements
      show that tracking of secondary ions provides a promising method for non-invasive
      monitoring of ion beam parameters for clinical relevant carbon ion fluences.
      Research with the pixel detectors was carried out in frame of the Medipix
      Collaboration.

PMID- 28517382
TI  - SU-D-213CD-01: 4D Ultrasound Calibration for Radiotherapy Guidance Using
      Automatic Intramodality Image Registration.
AB  - PURPOSE: In prior work we developed a robotic system providing real-time soft
      tissue ultrasound (US) volumes during radiotherapy beam delivery. for image
      guidance, the US volumes must be transformed to the linear accelerator reference
      frame. In this work we propose and characterize a new method of calibrating 4D US
      volumes based on automatic intramodality image registration. METHODS: A dynamic
      navigation link was used to port 3D US volumes from a Philips iU22 xMatrix
      machine to a PC in real-time. Sixty volumetric (3D) US images of a pelvic phantom
      were collected from various probe positions while the transducer's pose was
      monitored by an optical tracking system. US volumes were automatically registered
      to the first US volume using normalized mutual information. A system of equations
      was formulated and solved for the US probe-to-image transformation using the
      registration transformations and the optical tracking information. Accuracy of
      the US calibration was assessed on eight additional US volumes with two separate
      methods. In the first method, a set of three fiducial markers implanted in the
      phantom was manually selected in each volume by three individual readers.
      Selected marker locations were reconstructed in the stationary camera frame, and
      for each marker, mean distance to the reconstructed centroid was measured. In the
      second method, a bladder structure was semi-automatically segmented in each image
      volume. Mean distance between bladders segmented in a reference volume and the
      other seven volumes was computed. Calibration accuracy was also investigated as a
      function of the number of calibration images used. RESULTS: Mean error for the
      fiducial marker reconstruction was 2.3 mm. Mean distance error between segmented
      structures was 1.1 mm. The proposed calibration method typically converged with
      less than 20 images. CONCLUSION: Automatic image registration facilitates fast
      and simple US spatial calibration with accuracy under 2.3 mm using any US
      phantom. This work is supported in part by the Stanford University BioX program
      and by Philips Medical. Two of the authors of the abstract are employed by
      Philips Medical.

PMID- 28517383
TI  - SU-D-211-02: A Framework for 4pi Radiotherapy.
AB  - PURPOSE: Inclusion of highly non-coplanar treatment angles increases radiations
      dose conformality and critical organ sparing. However, implementation of this
      treatment strategy has been hampered by inaccurate solution space modeling,
      limited automated beam selection methods, the lack of efficient beam sequencing
      program and integrated collision prevention. The aim is to develop a 4pi
      radiotherapy paradigm that takes full advantage of modern computer-controlled
      robotic C-arm linear accelerators. METHODS: The beam geometry solution space was
      modeled by 3D surface scanning of the couch, gantry and patient. In order to
      utilize the entire solution space and optimize MLC resolution, variable source-to
      tumor distances were introduced. Conformai radiation doses were computed using
      convolution/superposition from uniformly distributed solid angles. Beam
      orientation optimization was performed using a column generation and pricing
      approach, which was also used to optimize beam fluence intensity modulation. A
      level set method was then employed to automatically sequence beams so the
      treatment time and couch motion can be minimized while avoiding collision on the
      path. RESULTS: The machine and patient surface was accurately measured and a
      cocoon shaped solution space was created with an integrated gap buffer of 4 cm.
      14 conformai beams were typically selected to maximize target dose coverage and
      minimize critical organ doses. Compared with manual non-coplanar and coplanar
      volumetric modulated arc therapy plans, an average 20% improvement was observed
      in high dose spillage, defined as the 50% isodose volume divided by the target
      volume, in a wide range of clinical cases including brain, lung, liver and
      partial breast cancer. CONCLUSIONS: We have established a framework that
      overcomes major technical difficulties associated with automated planning and
      delivery of highly non-coplanar treatment on the widely available C-arm linacs.
      Compared with coplanar volumetric modulated arc therapy plans, 4pi plans improve
      nearly all aspects of the dosimetry while remain highly deliverable.

PMID- 28517384
TI  - SU-D-217BCD-05: Analytic Determination of Size of Water Cylinder Absorbing Equal
      Radiation Dose as a System of Concentric Cylinders of Arbitrary Composition:
      Application for Pediatric CT.
AB  - PURPOSE: To develop analytic formulae for calculating absorbed dose to a system
      of concentric cylinders and to use this to determine the size of water cylinder
      which would absorb the same dose in a matching field. Appropriate scaling of
      radiation output to patient size is of particular interest in pediatric CT
      (TG204). METHODS: For a given CT scanner output, absorbed dose increases as
      patient size decreases. Analytic functions can calculate the dose delivered to
      systems of concentric cylinders of varying size and composition. In particular
      these functions provide useful insight when considering examinations in body
      regions with large variations in attenuation, such as the chest (which can be
      modeled as concentric cylinders of heart, lung, rib and soft tissue). Iterative
      calculations rapidly determine the size water cylinder required to absorb the
      same dose in matching radiation fields. More general findings put limits on some
      of the methods for determining size specific dose estimates (SSDE). RESULTS: For
      the simple chest model, in the absence of scatter or bow tie filter
      considerations, the equivalent water phantom would have a diameter of just over
      half the chest equivalent concentric cylinder phantom. A more general Result is
      that in the limit of very small size, the absorbed dose in a fixed irradiating
      field depends only on mass attenuation coefficient. CONCLUSIONS: The concentric
      cylinder model developed can be used to study the scaling of radiation dose with
      patient size. In particular, the water phantom absorbing the same dose as the
      chest region has only about half the diameter. An important conclusion is that in
      the limit of small size, absorbed dose depends on mass attenuation coefficient
      only and that in this limit an equivalent water phantom does not exist.

PMID- 28517386
TI  - SU-D-BRB-06: Comprehensive Population-Averaged Arterial Input Function (AIF) for
      DCE-MRI of Head and Neck Cancer.
AB  - PURPOSE: To generate a composite population-averaged(PA)-AIF for quantitative
      analysis of DCE-MRI data in head and neck (H&N) patients that is based on the
      right (RT) and left (LT) carotids, two pre-treatment scans, and one post
      treatment scan. METHODS: Twenty patients were imaged while undergoing concurrent
      chemoradiation (CRT) for H&N malignancies. The imaging protocol (1) included two
      baseline scans one week apart (Base1, Base2), and one scan 1 week post-CRT
      (Post). For each patient and time point, regions of interest (ROIs) in both the
      RT and LT carotids were drawn on coronal images. The plasma concentration curves
      of all ROIs were averaged and fit to a bi-exponential decay function to obtain
      the final PA- AIF (AvgAll). The ROIs were also divided by time point to obtain
      AvgBasel, AvgBase2, and AvgPost AIFs. The vascular transfer constant for both
      primary and nodes, Ktrans , was calculated (iCAD, Inc.) using the 4 AIFs, as well
      as the generic Weinmann's AIF. The median Ktrans values resulting from the AvgAll
      AIF were compared using Bland-Altman plots with the ones obtained from each
      individual time point. The Wilcoxon signed-rank test was used to compare the
      proposed AvgAll AIF and the generic AIF. RESULTS: The plasma parameters for the
      AvgAll AIF were a1,2=27.1135/17.6486 kg/liter, m 1,2=11.7525/0.2054 min-1 . The
      differences in Ktrans values using these coefficients vs. Weinmann's were
      statistically significant (p<0.0001). The median Ktrans values from the
      AvgBasel,AvgBase2, and AvgPost AIFs were, in most cases, not significantly
      different from the AvgAll values, indicating that the latter is appropriate
      foruse at all time points. CONCLUSIONS: A population-averaged AIF for H&N was
      generated that accounts for differences in RT vs. LT carotids, day-today AIF
      fluctuations, and treatment-induced AIF changes. It is not necessary to measure a
      post-treatment AIF to evaluate treatment-induced Ktrans changes.l. Craciunescu et
      al., MedPhys, 37, 6, 2683, 2010.

PMID- 28517385
TI  - SU-D-BRCD-01: Evaluation of Zebra Multi-Layer Ionization Chamber System for
      Patient Treatment Field and Machine QA for Spot Scanning and Passive Scattering
      Proton Beams.
AB  - PURPOSE: To evaluate Zebra multi-layer ionization chamber system for patient
      treatment field and machine QA for spot scanning proton beams (SSPB) and passive
      scattering proton beams (PSPB). METHODS: Zebra dose measurement system (IBA
      Dosimetry), consisting of 180 parallel platechambers with 2 mm detector spacing,
      was used for measuring proton beamdepth dose curves (DDC) for spread out Bragg
      peaks (SOBP) and single spot pristine Bragg peaks (PBP). The measurements were
      performed for 100 to 250 MeV PSPB and 89.2 to 221.8 MeV SSPB using the Hitachi
      ProBeat synchrotron based delivery system. An in-house Matlab based analysis
      software was used to compare the Zebra measured DDC with those measured by the
      Markus chamber in a PTW water tank (MC-WT). Several verification plans in the
      water phantom were created for patient treatment fields using the Eclipse
      treatment planning system (TPS). The DDC for individual verification fields were
      measured using the Zebra andcomparisons were made with the TPS calculations.
      RESULTS: The dosedifferences between the Zebra and MC-WT measurements in the
      plateau regions of the DDC are within 2% for various energies of PSPB, but are
      larger than 2% at the sharp dose distal gradient regions. The values for distal
      penumbra widths, range and SOBP widths from Zebra and MC-WT measurements agree
      within 0.5 mm, 1.5 mm, and 2 mm, respectively. The Zebra measured values of the
      range of the single spots also agreed within 1 mm with their established values
      from other measurements. The Zebra measured DDC of verification plan of patient
      treatment fields showed goodagreement with those from the TPS. CONCLUSIONS: Our
      investigation shows that Zebra can be useful for fast and reasonably accurate
      measurements of the DDC of pristine and spread-out Bragg peaks of both spot
      scanning and passive scattering proton beams.

PMID- 28517387
TI  - SU-D-213CD-04: Dosimetric Evaluation of HexaPOD as a Tool for Patient Setup
      Verification Accuracy.
AB  - PURPOSE: To quantify the dosimetric accuracy of 6 degrees vs. 3 degrees of motion
      for patient positioning for cone-beam CT and HexaPOD Evo RT system (Elekta, Inc.)
      using the ArcCHECK (Sun Nuclear Corporation, software v.6.0) QA phantom. METHODS:
      The average absolute values of our daily reported patient hexapod shift data were
      recorded and averaged for 18 patients. Using the CT scans of ArcCHECK, a QA plan
      was created in the Pinnacle (v.9.0) treatment planning system. By setting up
      ArcCHECK according to the QA plan and measuring the dose on Elekta Synergy, the
      baseline data was established. Next, an artificial shift was introduced in our
      phantom setup. A cone-beam CT scan of the phantom was obtained and images
      adjusted. The resulting translational and rotational shifts were recorded. The
      table was then moved according to the translational shifts only, and another
      measurement was taken. Next, using hexapod translational and rotational shifts,
      the table was moved in 6 degrees of motion, and the dose was re-measured.
      RESULTS: For 18 IMRT patients, the average translational shifts were: x= 0.53 cm,
      y=0.38 cm and z= 0.516 cm, and average rotational shifts were pitch=0.979 degrees
      , roll=0.8 degrees  and yaw= 0.67 degrees . The ArcCHECK phantom measured results
      were quantified using 3%, 3mm distance to agreement gamma analysis criteria when
      comparing measured to planned dose. Our measurements showed that an average 97.3%
      of the points agreed in plans with no shift. After the artificial shift was
      introduced, and cone-beam CT translational shifts were applied, 76.3% of points
      agreed. When both rotational and translational shifts were applied using Hexapod,
      an average of 93.4% of points agreed. CONCLUSIONS: Using hexapod for imaging and
      patient positioning results in a significantly more accurate dose delivery as
      compared to using only CBCT, as shown by our ArcCHECK QA phantom results.

PMID- 28517388
TI  - SU-E-E-01: Commissiong of Linear Accelerator and Beam Modeling in Treatment
      Planning Systems.
AB  - PURPOSE: Sooner or later every medical physicist is involved with commissioning
      and beam modeling of a new linear accelerator (linac) and a new treatment
      planning system (TPS). In spite of all instructions and training offered by the
      vendors, at the time a new linac is being purchased and added to the present ones
      the outside help is not so complete. The physicist who has to perform the
      commissioning job may not even be the one who was trained for that. What we are
      missing is a good comprehensive set of information and instructions on how to
      do's. From shielding calculation verifications, surveys, to collecting the beam
      data, modeling, entering the data into the TPS, and verifications of the goodness
      of the data we need a lot of support and we don't have it. I will provide a step
      by step description of the required work with the results we are looking for.
      METHODS: Presentation of the shielding calculations, survey required, tools
      needed to perform them. Detailed beam data collections, scanning system needed,
      machine set of specs needed, applicator details needed. Importing beam data from
      the scanning system and beam calculations. Algorithms used in dose calculation,
      IMRT optimization, heterogeneity corrections presented to be understood before
      modeling the beam data. RESULTS: At the completion of this course the medical
      physicist will be able to commission a linear accelerator and a treatment
      planning system with confidence and very little help from the outside.
      CONCLUSIONS: This compendium of detailed instructions on commissioning a linear
      accelerator will provide good uidance to every physicist who will be involved
      with the installation and bringing into safe use for treatment of a new linear
      accelerator.

PMID- 28517389
TI  - SU-D-217A-06: Impact of Anterior-Posterior (AP) and Posterior-Anterior (PA) Scout
      Scans on the CT Radiation Dose in the Whole Body PET/CT Scan.
AB  - PURPOSE: CT can contribute over 50% of radiation dose in the whole body (WB)
      PET/CT scan. Tube current modulation (TCM) is a standard technique for reducing
      CT radiation dose to the patient by changing the tube current with the patient
      size, and is controlled by a very low-dose scoutscan, which assumes the patient
      is positioned at the center of the CT gantry opening. However, most patients are
      not positioned at the center due to practicality or to avoid claustrophobic or to
      reduce time of radiation exposure from the patient to the technologist. We study
      the impact of the AP and PA scout scans to the patient radiation exposure from
      CT. METHODS: Ina retrospective study of 200 patients, each received two WB PET/CT
      scans: one with AP, and the other one with PA. The helical CT with TCM and PET
      acquisitions were identical in both scans. Separation of the two scans was about
      10 months in average. The scans were performed on four GE PET/CT scanners: three
      16- and one 64-slice with the same TCM settings. The 200patients were selected
      for the same scan coverage and similar body weight (difference = 3 kg). The tube
      current in each slice and average exposure tothe patient were recorded and
      compared. RESULTS: The AP scout caused lower radiation dose on 94% of the
      patients. Both the tube current, and radiation exposure were reduced by 46+/-30
      mA and 1.6+/-1.0 mGy, respectively. The effective radiation dose is reduced by
      1.7+/-1.2 mSv. These results were statistically significant (p<0.00001).
      CONCLUSIONS: The AP scout caused significantly less radiation dose than the PA
      scout in the CT scan of the whole-body PET/CT scan. Care should be taken to
      select theorientation of the scout scan to achieve appropriate radiation exposure
      to the patient when TCM is applied.

PMID- 28517390
TI  - SU-D-BRA-02: An Extended Time-Variant Seasonal Autoregressive Model-Based
      Prediction for Irregular Breathing Motion Tracking.
AB  - PURPOSE: Real-time tumor position/shape measurement and dynamic beam tracking
      techniques allow accurate and continuous irradiation to moving tumor, but there
      can be a delay of several hundred milliseconds between observation and
      irradiation. A time-variant seasonal autoregressive (TVSAR) model has been
      proposed for compensating the delay by predicting respiratory tumor motion with
      sub-millimeter accuracy for a second latency. This is the-state-of-the-art model
      for almost regular breathing prediction so far. In this study, we propose an
      extended prediction method based on TVSAR to be usable for various breathing
      patterns, by predicting the residual component obtained from conventional TVSAR.
      METHODS: An essential core of the method is to take into account the residual
      component that is not predictable by only TVSAR. The residual component involves
      baseline shift, amplitude variation, and so on. In this study, the time series of
      the residual obtained for every new sample are predicted by using autoregressive
      (AR) model. The order and parameters of the AR model is adaptively determined for
      each residual component by using an information criterion. Eleven data sets of 3
      D lung tumor motion, observed at Georgetown University Hospital by using
      Cyberknife Synchrony system, were used for evaluation of the prediction
      performance. RESULTS: Experimental results indicated that the proposed method is
      superior to those of conventional and the state-of-the-art methods for 0 to 1 s
      ahead prediction. The average prediction error of the proposed method was 0.920
      plus/minus 0.348 mm for 0.5 s forward prediction. CONCLUSION: We have developed
      the new prediction method based on TVSAR model with adaptive residual prediction.
      The new method can predict various respiratory motions including not only regular
      but also a variety of irregular breathing patterns and thus can compensate the
      bad effect of the delay in dynamic irradiation system for moving tumor tracking.
      A part of this work has been financially supported by Varian Medical Systems
      Inc., Palo Alto, CA and Japan Society for the Promotion of Science (JSPS), Japan.

PMID- 28517391
TI  - SU-D-213CD-06: Workflow and Safety Systems of a Linac-MR Sim-Brachytherapy
      MRgRTTM Facility.
AB  - PURPOSE: To develop the operational workflow and safety systems of a magnetic
      resonance-guided radiotherapy system (MRgRTTM), which comprises an MR scanner on
      rails that travels between a linac vault, MR simulation room and brachytherapy
      suite. METHODS: To develop a safe and streamlined clinical workflow, we conducted
      a comprehensive process review based on a layered approach to overall MRgRT
      safety that included i) facility design, (ii) workflow iii) system design and
      interlocks and iv) policies and procedures. We applied existing guidelines for MR
      and radiation safety, and employed system-level failure modes and effects
      analyses to design the MRgRT facility and clinical procedures. RESULTS: In the
      MRgRT system configuration, the MR and treatment systems are physically decoupled
      and used independently requiring novel administration of existing MR and
      radiation guidelines. A key element for the safe operation of the moving MR unit
      is the concept that all three rooms represent zone 4 areas (American College of
      Radiology guidelines). Using this concept, we applied MR guidelines to develop
      safe procedures for the overall suite, including screening of all persons
      entering the suite in zone 2 and control of ferromagnetic materials. We generated
      a clinical workflow that ensures expedient and safe transition between MR imaging
      and treatment delivery in both the linac and brachytherapy rooms. In addition, we
      designed emergency protocols for MRgRT, which helped drive requirements for the
      facility and system design, e.g., need for an accessible MR-safe stretcher.
      CONCLUSIONS: We designed the first comprehensive description of the MRgRT
      workflow, interlocking systems and safety procedures. With this layered approach
      to safety, we addressed critical aspects regarding safe operation and workflow
      for the system and provided multiple redundancies for key processes. Coupled with
      customized staff training, the proposed design ensures the safe operation of the
      MRgRT facility. This work has received research personnel support from IMRIS.

PMID- 28517392
TI  - SU-D-213AB-02: Optimal Design of Multichannel Vaginal Cylinder Applicators for
      High Dose Rate Brachytherapy.
AB  - PURPOSE: To determine the optimal location of catheters in multichannel vaginal
      applicators to appropriately cover the vaginal cuff target and minimize dose to
      the organs at risk (OARs) and hot spots in the target. METHODS: A new
      multichannel vaginal applicator with a diameter of 30 mmconsists of a single
      central catheter and an outer array of eight catheters. A total of 20 plans were
      generated from 5 patients by using different outer catheter locations at r = 4,
      8, and 12 mm. The target was defined as a 5 mmcircumferential shell extending 4
      cm in length around the applicator, excluding the bladder, rectum, and bowel. An
      inverse planning simulated annealing algorithm and graphical optimization was
      applied to ensure the prescription dose (7.0 Gy per fraction) covered >97% of the
      target and minimized dose to the OARs. Target coverage (D90 and V100), hot spots
      (V150 and V200), and OAR doses (D0.1cc, D1cc, and D2cc) from the various catheter
      placements were compared to single catheter plans. RESULTS: By study design all
      plans had the same target coverage D90 (105.0- 108.3%) and V100 (97.1-97.2%). The
      V150 and V200 were 16.1% and 3.4% (r=0mm), 17.3% and 4.2% (r=4mm), 20.1% and 2.2%
      (r=8mm), and 30.1% and 6.0% (r=12mm). The DO.1cc to the OARs from the various
      catheter placements at r = 4, 8, and 12 mm was reduced by 4.0%, 8.6%, 11.9%
      (bladder), 7.4%, 13.2%, and 17.4% (rectum), when compared to the central catheter
      plans. CONCLUSIONS: Multichannel vaginal applicators provide better dosimetry
      than single channel applicator. The catheter array located closest to the
      applicator surface most significantly reduces dose tothe OARs at the expense of
      larger hot spots in the target. The array in the middle of the applicator radius
      provides significantly decreased dose to the OARs and gave relatively smaller hot
      spots.

PMID- 28517393
TI  - SU-D-218-04: Evaluation of the Performance of the Solid State X-Ray Image
      Intensifier (SSXII) Using Generalized Metrics.
AB  - PURPOSE: To evaluate the performance of the Solid State X-ray Image Intensifier
      (SSXII) using generalized linear-system metrics and to study the effect of
      different scatter fractions, object magnifications, and focal spots onits
      performance. METHODS: The SSXII is a high-resolution and high- sensitivity region
      of-interest x-ray imaging detector that provides real-timeimaging with low
      instrumentation noise. To evaluate the total system performance for a clinical
      environment, we used generalized metrics that include the effects of scattered
      radiation, finite focal-spot size, and geometric unsharpness. For comparison, a
      commercial standard flat-panel detector (FPD) was used. The focal-spot MTF was
      obtained by taking theFourier Transform of the point-spread function of x-ray pin
      hole images. The detector MTF was measured using the standard edge method. The
      scatter MTF was simulated with a theoretical model. We have calculated the GMTF
      and GDQE for the SSXII and FPD. Three focal-spots (small, medium, and large),
      different object magnifications and scatter fractions were used for the GMTF and
      GDQE comparison. RESULTS: The GMTF andthe GDQE were shown to be degraded
      significantly from that of the detectoralone at the higher spatial frequencies
      because of blur due to the finite sizeof the focal-spot, and at the lower
      frequencies because of scatter. Furthermore, the degradation increases even more
      as the focal-spot size,object magnification and scatter fraction increases. The
      GMTF and the GDQE for the FPD were similar to those of the SSXII at lower
      frequencies, but were limited to frequencies below its 2.5 cycles/mm Nyquist
      frequency due to the 194-micron pixel size compared to the 18.9 cycles/mm Nyquist
      frequency of the 26.4-micron pixel-size SSXII. CONCLUSIONS: This work
      demonstrates that the SSXII and the FPD have similar performance at thelower
      spatial frequencies, whereas, the SSXII demonstrates superior performance over
      the FPD at higher frequencies. Supported in part by: NIH Grants R01-EB008425, R01
      EB002873 and an equipment grant from Toshiba Medical Systems Corp.

PMID- 28517394
TI  - SU-D-BRB-01: 4D-CT Lung Ventilation Images Vary with 4D-CT Sorting Techniques.
AB  - PURPOSE: 4D-CT ventilation imaging is a novel promising technique for lung
      functional imaging and has potential as a biomarker for radiation pneumonitis,
      but has not been validated in human subjects. The current 4D- CT technique with
      phase-based sorting results in artifacts at an alarmingly high frequency (90%),
      which may introduce variations into ventilation calculations. The purpose of this
      study was to quantify the variability of 4D- CT ventilation imaging to 4D-CT
      sorting techniques. METHODS: Two 4D-CT images were generated from the same data
      set by: (1) phase-based; (2) anatomic similarity- and abdominal displacement
      based sorting for five patients. Two ventilation image sets (V_phase and V_anat)
      were then calculated by deformable image registration of peak-exhale and peak
      inhale4D-CT images and quantification of regional volume change based on
      Hounsfield unit change. The variability of 4D-CT ventilation imaging
      wasquantified using the voxel-based Spearman rank correlation coefficients and
      Dice similarity coefficients (DSC) for the spatial overlap of segmented low-
      functional lung regions. The relationship between the abdominal motionrange
      variation and ventilation variation was also assessed using linearregression.
      Furthermore, the correlations between V_phase or V_anat and SPECT ventilation
      images (assumed ground-truth) were compared. RESULTS: In general, displacement-
      and anatomic similarity-based sorting reduced 4D- CT artifacts compared to phase
      based sorting. The voxel-based correlationsbetween V_phase and V_anat were only
      moderate (range, 0.57-0.77). The DSCs for the low-functional lung regions were
      moderate to substantial (0.58-0.70). The relationship between the motion range
      variation and ventilation variation was strong on average (R2=0.79+/-0.25),
      suggesting that ventilation variations are related to 4D-CT artifacts. Vanat was
      found to improve correlations with SPECT ventilation images compared to V_phase.
      CONCLUSIONS: 4D-CT ventilation images vary markedly with 4D-CT sorting
      techniques. 4D-CT artifacts should be considered as a significant source of
      variation in 4D-CT ventilation imaging during its validation. This study
      wassupported in part by NIH/NCI R01 93626. SK and CL are employees ofPhilips
      Research.

PMID- 28517395
TI  - SU-D-BRA-06: Investigation of Prostate Intrafractional Motion during External
      Beam Radiotherapy for a Large Patient Population.
AB  - PURPOSE: To analyze and report prostate intrafractional motion recorded online
      during external beam radiotherapy and to provide guidance for advanced prostate
      IMRT. METHODS: Prostate intrafractional motion during IMRT and RapidARC
      treatments was tracked and recorded using a Calypso 4D-localization system. Data
      for 8600 treatment fractions of 230 prostate patients was analyzed. The
      percentage of treatment fractions, the fractional treatment time, and the
      fractional time of any individual minute were analyzed separately for prostate
      movements greater than the thresholds (2, 3, 5 and 7mm). RESULTS: The percentages
      of fractions in which prostate shifted more than the thresholds for a duration
      >10 seconds are 66.2%, 34.9%, 8.9% and 2.6% (57.9%, 27.9%, 5.2% and 0.8% for >30
      seconds duration), respectively. For 10 patients who exhibited the largest
      motion, the percentages are 95.2%, 76.0%, 43.2% and 14.7% (91.3%, 72.4%, 36.3%
      and 6.0% for >30 seconds duration). The fractional time for motion larger than
      the thresholds is 27.8%, 10.7%, 1.6% and 0.3% (56.2%, 33.7%, 11.2% and 2.1% for
      these patients). The posterior-direction motion is significantly higher than
      those in other directions. The fractional time of an individual minute with shift
      >3mm is higher at the 10th minute than at the 5th minute (20% vs. 10%) after the
      initial setup. For treatments completed within 5 minutes, the average fractional
      time with motion >3mm was lower than those within 10 minutes (4% vs. 12%).
      Irregular movements were observed most likely in the first minute after patient's
      setup, which were 12% and 7% among all fractions with movements >2mm and >3mm,
      respectively. CONCLUSIONS: The prostate intrafractional motion was within 3mm for
      most treatment fractions. However, larger movements were observed for some
      patients, who require real-time corrections or larger treatment margins. The
      results indicate that it is beneficial if the treatment can be completed within 5
      minutes.

PMID- 28517396
TI  - SU-D-211-01: Effect of Immobilization/support Devices and Air Gap on Skin Doses
      for Stereotactic Body Radiotherapy with Abdominal Compression Device.
AB  - : Purpose To evaluate the effects of the couch, the immobilization/support
      devices, and air gap on the skin dose for SBRT treatment with abdominal
      compression device and to investigate strategies to minimize skin dose by phantom
      measurementMaterial and methodsSkin-sparing comes from lower dose in buildup
      region, anything added between tissue and air may change buildup PDD curve hence
      skin dose increases. To investigate such effects due to different buildup
      materials and air gap between the buildup material and the surface, we employed
      EBT2 film in slab and water phantoms to measure doses at depths varying from
      surface to dmax, field sizes (4*4 to 10*10 cm2 ), and air gaps from 5 to 15 cm
      for 6 MV photons. Measured dose was normalized to dose at dmax for a 10*10 cm2
      field. The buildup materials included table tops (tennis net, Exact Couch and
      Indexed Immobilization table tops), vacuum bags (Civco Vac-Lok and Med-Tec
      cushions), and body frames (Elekta stereotactic body frame and Civco Body Pro
      Loc). ResultsThe relative doses at depth of 1.00 mm were 0.63 with no buildup,
      0.90 with couch+6cm bag, 0.91 with bodyframe+bag, and 0.96 with
      couch+bodyframe+bag for a 4*4 cm2 field. With a 10*10 cm2 field, the above values
      changed to 0.67, 0.94, 1.01, and 0.97, respectively. Thick bag (6.0cm) increased
      skin dose by 10% comparing to the thinner bag (1.5cm). For a buildup (couch +
      body frame) plus air gap, the relative doses were 0.73, 0.84, and 0.91 for air
      gap of 15.0, 10.0, and 5.0 cm, respectively, for a 10*10 cm2 field. CONCLUSIONS:
      The skin dose increases by up to 40% if patient was treated through the
      immobilization device or couch. Skin dose also increased with increasing field
      size. Introduction of large air gap may recover much of the lost buildup effect.

PMID- 28517397
TI  - SU-D-217BCD-04: How Do We Know How Low Can We Go in Lung Cancer Screening CT?
AB  - PURPOSE: To demonstrate a technique for determining the acceptable radiation dose
      level for lung cancer screening CT. METHODS: 20 patients who underwent a
      clinically indicated routine chest CT scan with 120 kV and 180 quality reference
      mAs were enrolled in this IRB approved study. Automatic exposure control was used
      to adjust for patient size. Scanner output, as expressed in CTDIvol, varied
      accordingly (mean=16.8 mGy, range=7.6 to 26.6 mGy). A previously validated noise
      insertion software tool developed in our lab was used to simulate scans acquired
      with reduced dose levels (12.5%, 25%, 50% of the original dose level). Images
      reconstructed from the same raw data but at the original and simulated, reduced
      dose levels were randomized and blindly reviewed by three thoracic radiologists.
      Lung and soft tissue regions were graded for two different imaging tasks: 1)
      routine diagnostic CT exam of the chest and 2) screening exam of the chest for
      lung cancer. A 5 point scale was used to rate each exam for each task (1=too
      noisy, significantly impacted confidence to 5=excellent quality, excellent
      confidence). Exams were considered acceptable when at least two of the three
      radiologists gave a score of 3 or higher. The percentage of patients meeting this
      definition of acceptable was calculated for each imaging task, dose level, and
      tissue type (lung or soft tissue). RESULTS: The percentages of exams considered
      acceptable for the purpose of lung cancer screening were 90%, 100%, 100%, 100%
      (lung tissue) and 85%, 100%, 100%, 100% (soft tissue) at 12.5%, 25%, 50% and 100%
      of original dose level. For the purpose of routine diagnostic chest CT, the
      percentage of acceptable exams were 75%, 95%, 100%, 100% (lung tissue) and 35%,
      85%, 90%, 100% (soft tissue) at 12.5%, 25%, 50% and 100% of original dose level.
      CONCLUSIONS: At 25% of the dose used for routine diagnostic chest CT at our
      institution, acceptable image quality for the purpose of CT screening for lung
      cancer was achieved in 100% of the evaluated cases. This factor of 4 in dose
      reduction relative to routine chest exams is similar to what was used in the NLST
      trial.

PMID- 28517398
TI  - SU-D-213AB-06: Surface Texture and Insertion Speed Effect on Needle Friction.
AB  - PURPOSE: High frictional forces between the needle surface and tissue cause
      tissue deflection which hinders accurate needle placement for procedures such as
      brachytherapy and needle biopsy. Accurate needle placement isimportant to
      maximize procedure efficacy. This work investigates how needle surface roughness
      and insertion speed affect the frictional forcebetween a needle and tissue.
      METHODS: A friction experiment was conducted to measure the force of friction
      between bovine liver and three 11 gauge needles having Ra surface roughness of
      3.43, 1.33, and 0.2 MUm. Each of the three needles were mounted on a linear slide
      and were advanced and retracted through bovine liver at speeds of 50, 100, 150,
      and 200 mm/s for a total of 12 trials. In each trial the needle was advanced and
      retracted in 10 cycles producing a steady state insertion force and a steady
      state retraction force for each cycle. A force sensor connecting the needle to
      the linear slide recorded the resistance force of the needle sliding through the
      liver. The liver was mounted in a box with a pneumatic cylinder which compressed
      the liver sample by 11.65 kPa. RESULTS: The roughest needle (Ra = 3.43 MUm) on
      average produced 68, 73, 74, and 73% lower friction force than the smoothest
      needle (Ra = 0.2 MUm) for the speeds of 50, 100, 150, and 200mm/s, respectively.
      The second roughest needle (Ra = 1.33 MUm) on average produced 25, 45, 60 and 64%
      lower friction force than the smoothest needle (Ra = 0.2 MUm) for the speeds of
      50, 100, 150, and 200 mm/s, respectively. CONCLUSIONS: Rougher needle surface
      texture and higher insertion speed reduced frictional forces between the tissue
      and the needle. Future studies will examine how frictional forces can be modeled
      and predicted given surface texture and insertion speed.

PMID- 28517399
TI  - SU-D-BRB-05: Small Animal Lung Compliance Imaging: Assessment System for Tissue
      Sensitivity to Radiation Induced Lung Injury.
AB  - PURPOSE: Recent clinical trials and animal studies have indicated that the tissue
      sensitivity to radiation induced lung injury (RILI) may be region- specific. In
      this study, we propose a new 4D cone beam CT (CBCT) basedcompliance imaging
      method to measure regional pulmonary function change in precisely irradiated
      small animal under CBCT guidance on small animal radiation research platform
      (SARRP) to facilitate our understanding of region-specific tissue sensitivity to
      RILI. METHODS: Four Sprague-Dawley rats underwent prospective pressure gated 4D
      CBCT on SARRP. Three animals were selected as control group which underwent a
      second 4D CBCT scan. The fourth animal was irradiated in the central lung (24 Gy)
      using 3 * 3 mm collimating cone 2 months prior to the scan. The specific
      compliance (Csp) was calculated via the real time pressure measurement from the
      ventilator and displacement field from 3D B-spline image registration between the
      end of inhale and end of exhale phases from the 4D CBCT scan. The 3D Csp maps
      from the control animal group were mapped to the irradiated animal as a Csp
      functional atlas for statistical analysis. We alsoevaluated the repeatability of
      the Csp measurement on a voxel-by-voxel basis. RESULTS: No significant Csp
      difference is found after two month of radiation between the irradiated rat
      (0.22+/-0.05) and the functional atlas (0.21+/-0.07). The observation is
      consistent with previous publications. The averaged linear correlation
      coefficient between the voxel-by-voxel Csp measurements from initial and repeat
      scans in control group is 0.98. CONCLUSIONS: We proposed a method that uses 4D
      CBCT based compliance imaging to measure region-specific tissue sensitivity of
      RILI. We compared the irradiated animal two months after radiation with the
      control group. Our study shows an excellent robustness of the proposed method for
      regional lung tissue specific compliance measurement. This work was supported in
      part by UVa George Amorino Pilot Grant.

PMID- 28517400
TI  - SU-D-213CD-03: Live Video-Guided Volumetric Tracking of Respiration Motion.
AB  - PURPOSE: To introduce video surface imaging guidance in synchronization with 4D
      cone-beam CT (CBCT) scans, and in combination with respiration- gated or target
      tracked dose delivery to treat mobile tumors, without collaterally damaging
      nearby critical structures. METHODS: The approach uses the concept that the
      integral of balanced forces over the moving surfaces is directly proportional to
      the lung volume changes. The respiratory motions, representing the lung volume
      variations, were measured with the dynamic volume under the moving surfaces of
      the thorax and abdomen. Sequential surface images on several patients and
      volunteers were acquired for the feasibility study. Respiratory motions were
      repeatedly measured on volunteers undertaking a quiet (normal) or a forced (deep)
      breath. The dynamic volume under the moving surfaces were robustly fitted with a
      linear trend and a trigonometric wave function that was compared with the fitted
      curves for target moving trajectories derived from forty 4D-CBCT scans. RESULTS:
      A large chest wall superior-outward movement was the unique characteristic of a
      forced breath that had doubled the volume variations and elongated the
      respiration period from quiet breath of ~4 seconds to >6 seconds. Under a quiet
      breath, target motion trajectories could be easily described by single sine
      functions that were consistent with dynamic surface volume modeling except for
      having different motion amplitudes. The accuracy in synchronization of the real
      time surface motion with respiration motion was within the measurement
      uncertainty of ~2 mm. CONCLUSIONS: The analytical results with a hypothetical
      single sine platform allow us to accurately predict internal target motion with
      use of real-time video images. Synchronization of dynamic volume with respiratory
      motion appears applicable for association of 4D medical imaging with 4D
      videoimaging.

PMID- 28517401
TI  - SU-D-211-05: A Systematic Analysis of Penumbra Characteristics in Conformai Arc
      Delivery for SBRT and Its Utilization for Negative Margin Technique (NMT), a
      Novel Planning Strategy for Improving Dose Conformation.
AB  - PURPOSE: To systematically analyze penumbra characteristics in co-planar arc
      beams and demonstrate how optimal aperture margin (OAM) can be systematically
      estimated. METHODS: Full arc-beam delivery was simulated with a Pinnacle RTP for
      a total of 32 cases. Considered factors were energy (6X, 6F, 10X, and 10F, where
      'F' indicates flattening-filter-free), field-size (2*2, 4*4, 6*6, and 8*8), and
      two materials (50*50*50 cm*cm*cm water and 50*50*50 cmxcmxcm water with a 20 cm
      diameter sphere of 0.25 g/cc lung density at the center). The highest-dose
      gradient (HDG) and its range in both radial-dose-distribution (RDD) and
      longitudinal-dose-distribution (LDD) were evaluated. For OAM estimation, start
      with simulated dose distributions in interest. Measure coverage size (CS) at the
      chosen PIL in the RDD. The difference between the target size (TS) and the CS is
      the margin needed. In radial-direction, choose a PIL where the CS is larger than
      the TS [resulting in 'negative margin (NM)'] to enhance conformation
      capability.Next, measure the CS at the chosen PIL in the LDD. Longitudinally,
      positive margin is expected in general. This process was applied to 6X and 10F
      cases in lung to illustrate its applicability. RESULTS: Overall, larger HDG was
      observed in 6 MV (than 10 MV), smaller fields, LDD (than RDD), and in water (than
      lung). 6F showed slightly larger HDG than 6X while 10X did than 10F. Dose fall
      off started significantly farther from the CAX in RDD than LDD, supporting the NM
      concept. With the systematic margin estimation applied, expected PILs matched
      closely with isodose points having tight target coverage, indicating the
      applicability of the method. CONCLUSIONS: Among tested, the 6F beam provides the
      most optimal dose distribution for dose conformation. The range of optimal PIL
      decreases as field-size increases. It has been demonstrated optimal AMs can be
      systematically estimated as proposed in this study.

PMID- 28517402
TI  - SU-D-217A-02: Effects of Enegy-Window Width and Spectral Effective Energy on
      Estimation of Gamma Camera Deadtime Using the Decay Method.
AB  - PURPOSE: Assessment of count-rate performance (CRP) is part of routine quality
      assurance (QA) for gamma cameras. Manufacturers often specify deadtime (t) based
      on the NEMA decay method (NEMA 1-2007). The spectral conditions prescribed by
      NEMA are often difficult to duplicate during routine clinical QA testing and the
      appropriate energy window is poorly defined. The objective of this investigation
      is to evaluate the effects of energy-window selection and spectral conditions on
      estimates of t using the NEMA decay method. METHODS: CRP was evaluated
      intrinsically over a period of 48 hours with Tc-99m for two Siemens Symbia gamma
      camera detectors using the NEMA decay method. CRP measurement was repeated with
      varying amounts of scattering material (0-8 cm of acrylic) placed between the
      source and detectors to transform the incident spectrum. CRP measurements were
      also repeated using different photopeak-window widths (2-75%) as well as an open
      energy-window. The CRP data were fit to the paralyzable detector model via non
      linear least-squares minimization to estimate t. RESULTS: Estimates of t
      increased linearly with decreasing spectral effective energy. The effective
      energy was varied from 142-to-99 keV, which consequently altered the estimates of
      t by ~0.095MUs or 21% (p<0.01). Additionally, estimates of t increased as a power
      law when the fraction of measured counts in the photopeak window decreased
      relative to open-window (total) counts. The ratio photopeak-window counts to open
      window counts were varied from 1-to-0.12 which consequently altered the
      estimates of t by ~8MUs or 180%. The estimated change in t between 15% and 20%
      photopeak window is -0.13MUs or 12.5%. Repeat measurements demonstrated that
      estimates of t using the decay method are precise to <2%. CONCLUSIONS: Deadtime
      (t) determined using the decay method varied significantly with the spectral
      effective energy and photopeak-window width. Careful attention to measurement
      conditions are imperative when measuring t using the decay method for comparison
      against manufacturer's specifications or trending as part of routine QA program.

PMID- 28517403
TI  - SU-D-217A-05: Auto-Registration of Cardiac PET/CT Images with a 3D Weighted
      Gradient Correlation Algorithm.
AB  - PURPOSE: To design a novel 3D automatic registration algorithm for cardiac PET/CT
      registration using gradient information and to evaluate the performance of the
      algorithm with clinical PET/CT datasets. METHODS: The 512*512*47 CT images are at
      first resized to 128*128*47 to match the matrix size of PET. In order to maximize
      the gradient information at boundaries in CT, a conventional fuzzy c-means
      clustering algorithm (number of cluster = 7) is implemented to suppress signals
      from tissues that do not contribute much useful information for the registration
      purpose (fat, lung, and bones). The 3D Image gradient map, consisting of all
      three orthogonal components, is derived from the PET images and the post-
      clustering CT images. The mis-registration is modeled as 3D rigid body
      translation in this study, though it can be extended to include rotations as
      well. The details of the gradient-based objective function are described in the
      support document. Optimal registration is determined by searching for the maximum
      of the objective function over a range of potential translation positions (e.g.
      8.2*8.2*2.8cm). This process is repeated at a higher matrix size (512*512*47) to
      refine the result of registration. RESULTS: We applied this auto registration
      technique on 55 patient data sets of cardiac PET/CT images. The CT images were
      average-CT images, and the PET images were without attenuation correction. 54 out
      of the 55 cases produced satisfactory registration. CONCLUSIONS: The proposed
      weighted gradient correlation algorithm is a viable solution for auto
      registration of cardiac PET/CT images. More work is needed to further improve the
      robustness of thealgorithm.

PMID- 28517404
TI  - SU-E-E-04: Building and Strengthening the First Master's Program in Medical
      Physics in The Gulf Region.
AB  - PURPOSE: The first medical physics Master's program in the Arabian Gulf region
      was started in 2002 at King Fahd University of Petroleum & Minerals (KFUPM),
      Dhahran, Saudi Arabia. METHODS: After consulting with national and international
      representatives from the AAPM, IOMP, the University of Wisconsin-Madison and King
      Faisal Specialist Hospital and Research Center (KFSHRC) we constructed a
      versatile and rigorous curriculum. The program requires the completion of 7 core
      courses, 7 required labs, a minimum of 3 elective courses, a research project, a
      four-month clinical rotation and passing and a comprehensive examination. The
      success of the program required very close collaboration with national hospitals
      such as King Fahad Specialist Hospital in Dammam (KFSH-D), KFSHRC, and Riyadh
      Military Hospital. We cemented the collaboration with a formal agreement between
      KFUPM and KFSH-D, whereby the clinical medical physicists are actively involved
      in teaching lectures and labs, evaluating students' performance and co
      supervising their clinical rotation and research projects. In order to prepare
      our graduates for their medical physics careers, we emphasize innovative learning
      methods such as students centered learning, execution of course projects,
      experiential learning and acquiring research skills and tools such as Monte Carlo
      simulations. RESULTS: Our graduates have succeeded in securing clinical positions
      in some of the best hospitals in the region and achieved high employer
      satisfaction. Some students have gone to pursue their PhD's in North America and
      Europe. Many of our students succeeded in publishing their projects in
      international journals and international conferences. One of our students was
      instrumental in obtaining a US patent (US Patent # 785298) for an innovative x
      ray tube design. CONCLUSIONS: We have achieved national recognition through the
      excellence of our graduates. In order to maintain high education quality
      standards and achieve international recognition, we are presently working to
      acquire IAEA approval and CAMPEP accreditation.

PMID- 28517405
TI  - SU-D-213CD-05: Identifying Prostate Brachytherapy Seeds at MRI: A Study in
      Phantom.
AB  - PURPOSE: Conventionally, post-implant CT scans are used for identification of
      prostate brachytherapy implant seed locations. The dosimetric quality of the seed
      implant in our institution is evaluated based on CT/MRI fusion and contouring of
      prostate and rectal wall on MRI. Post-implant evaluation of prostate
      brachytherapy using MRI alone is generally not feasible due to the uncertainty
      associated with seed localization despite its excellent anatomical delineation.
      The fusion of CT and MRI has some variability and may be time consuming. The goal
      of our current work was to use SWI phase images for identification of prostate
      brachytherapy seeds. Using MRI alone to identify seeds will eliminate the need
      for CT scan of the patient post-implant and eliminate the variability of the
      CT/MRI fusion. METHODS: A prostate gel phantom containing five inactive brachy
      seeds (Advantage I-125TM, Biocompatibles, Oxford, CT) each has longitudinal cross
      section area of 3.6 mm2. It was assessed using CT, and MRI. Imaging was done
      using a GE Signa 3T HD MRI system (GE Heathcare, Millwaukee, WI). Imaging
      parameters for SWI were: 512*384 (zero filled to 512*512), FOV=10 cm, ASSET
      factor=2, TE/TR=20/42 ms, FA=15 degrees , RBW= 80 Hz/pixel, spatial
      resolution=0.3 * 0.3 * 2.0 mm. RESULTS: Brachytherapy seed, as confirmed on CT
      images, were easily identified in the phantoms on the filtered SWI phase images.
      The mean area for the 5 seeds, as measured on CT and SWI filtered phase images,
      was 3.5+/-0.5 mm2 and 3.8+/-0.6 mm2 , respectively. There appeared to be linear
      relationship in seed area as determined by SWI filtered phase compared to CT
      (R2=0.8). CONCLUSIONS: With the improved resolution, SNR and proper filtering on
      high field MRI systems, SWI phase images can be used to identify prostate
      brachytherapy seeds on conventional MRI without using CT.

PMID- 28517406
TI  - SU-D-213AB-01: Dosimetry Improvement and Needle Number Reduction in Prostate
      Brachytherapy Using Electromagnetically Guided Needle Placement.
AB  - PURPOSE: To investigate dosimetry improvement in prostate brachytherapy by
      conforming needles to urethral and prostate shape using an electromagnetic
      tracking device. METHODS: We have reported a needle tracking system using an
      electromagnetic sensor embedded inside the tip of the needle to improve needle
      reconstruction accuracy and efficiency in conventional prostate HDR
      brachytherapy. Utilizing the same system, we propose to guide needle insertion
      following pre-optimized tracks based onthe target shape. In this study, we
      investigate possible dosimetry improvement and needle number reduction by
      comparing plans using the conventional implant method and the proposed method.
      Twelve prostate brachytherapy patients were selected and studied retrospectively.
      New virtual plans were created using the proposed method and conforming needle
      tracks to the urethral and prostate shapes. Same optimization constraints were
      applied to both the conventional and the new plans. DVH parameters and total
      needles used have been analyzed to quantify dosimetry improvement and potential
      toxicity sparing due to reduction in implant needles. RESULTS: Prostate volumes
      are 41.16+/-13.27 cc. Number of needles used for the conventional plan is 16.6+/
      1.2, vs. 13 for all the new plans. The prostate volume receiving 100% (V100),
      125% (V125), and 150% (V150) of the prescription dose in conventional plans vs.
      those in the new plans are 99.48%+/-0.21% vs. 99.53%+/-0.20%, 53.90%+/-5.61% vs.
      50.30%+/-5.23%, and 25.37%+/-4.91% vs. 20.96%+/-3.41%, respectively. The
      corresponding urethra V100 and V110 are 90.96%+/-3.10% vs. 85.78%+/-7.76% and
      2.06%+/-1.23 vs. 0.46%+/-0.28%. CONCLUSIONS: The needle numbers and the urethral
      V110 in the new plans are significantly lower than those in conventional
      plans(p<0.001 and p=0.004, respectively), with no significant changes in doses
      tothe prostate. Conformai needle implant following pre-optimized tracks with
      electromagnetic guidance may significantly reduce acute and late toxicities in
      prostate brachytherapy by reducing the number of needles and theurethral doses.

PMID- 28517407
TI  - SU-D-218-03: Resonant Frequency of Rotating Anode X-Ray Tubes.
AB  - PURPOSE: To evaluate a new rotating anode X-ray tube from the resonant frequency
      point of view for stable and safe operation, and to validate a finite element
      model for insight into X-ray tube rotor dynamics and vibration. METHODS: The 3
      dimensional FEM model of the X-ray tube motor has been developed using ANSYS and
      COMSOL. The resultant resonant frequency from the FEM simulation is substantiated
      by experiments. During deceleration of the X-ray tube, an accelerometer and a
      corresponding amplifier send the time domain vibration response to a spectrum
      analyzer which generates the power spectrum. In the frequency domain analysis, a
      peak signifies large vibrations at that frequency. To corroborate the FEM model,
      the resonant frequency of the motor assembly without the anode attached was also
      measured. Lastly, a rough estimate of the resonant frequency can also be observed
      in angular speed curves which are obtained utilizing a quadrature position
      sensor. RESULTS: The first mode resonance is expected at 20.3 Hz from the FEM
      simulation. This result matches closely with the peak at 22.2 Hz in the power
      spectrum and the location of the abrupt decreasing acceleration (slope) in the
      speed curve at 22 Hz. Without the anode, the FEM simulation result of 35.1 Hz is
      equal to the first peak at 35.1 Hz, and the angular acceleration is suddenly
      reduced at 34.4 Hz. CONCLUSIONS: For image-guided interventional procedures using
      a hybrid system, the X-ray tube should create flux at various times requiring
      repeatedacceleration and deceleration of the motor. Hence it is ideal that the
      resonant frequency is higher than operational speed, although alternatively the
      motor could accelerate through the resonant frequency quickly. Design
      improvements to modify the location of resonance of our motor assemblyare
      underway using the verified FEM model. NIH R01 EB007626, Richard M. Lucas
      Foundation.

PMID- 28517408
TI  - SU-D-BRCD-06: Measurement of Elekta Electron Energy Spectra Using a Small
      Magnetic Spectrometer.
AB  - PURPOSE: To demonstrate how a small magnetic spectrometer can measure the energy
      spectra of seven electron beams on an Elekta Infinity tuned to match beams on a
      previously commissioned machine. METHODS: Energyspectra were determined from
      measurements of intensity profiles on 6"-long computed radiographic (CR) strips
      after deflecting a narrow incident beam using a small (28 lbs.), permanent
      magnetic spectrometer. CR plateexposures (<1cGy) required special beam reduction
      techniques and bremsstrahlung shielding. Curves of CR intensity (corrected for
      non- linearity and background) versus position were transformed into energy
      spectra using the transformation from position (x) on the CR plate to energy (E)
      based on the Lorentz force law. The effective magnetic field and its effective
      edge, parameters in the transformation, were obtained by fitting a plot of most
      probable incident energy (determined from practical range) to the peak position.
      RESULTS: The calibration curve (E vs. x) fit gave 0.423 Tesla for the effective
      magnetic field. Most resulting energy spectra were characterized by a single,
      asymmetric peak with peak position and FWHM increasing monotonically with beam
      energy. Only the 9-MeV spectrum was atypical, possibly indicating suboptimal beam
      tuning. These results compared well with energy spectra independently determined
      by adjusting each spectrum until the EGSnrc Monte Carlo calculated percent depth
      dose curve agreed well with the corresponding measured curve. CONCLUSIONS:
      Results indicate that this spectrometer and methodology could be useful for
      measuring energy spectra of clinical electron beams at isocenter. Future work
      will (1) remove the small effect of the detector response function (due to
      pinhole size and incident angular spread) from the energy spectra, (2) extract
      the energy spectra exiting the accelerator from current results, (3) use the
      spectrometer to compare energy spectra of matched beams among our clinical sites,
      and (4) modify the spectrometer to utilize radiochromic film.

PMID- 28517409
TI  - SU-D-BRA-05: Prostatectomy Patient's Bladder and Rectum Inter-Fraction Organ
      Motion and Deformation Can Be Described by a Gaussian Signed Distance Field.
AB  - PURPOSE: The inter-fraction organ motion/deformation can be conveniently modeled
      using Bayesian theory with Normal-gamma conjugate prior if signed distance from
      any fixed point in space to surface of the organ of interest obeys normal
      distribution. In this study, we investigated whether the inter-fraction
      motion/deformation of bladder and rectum observed from clinical prostatectomy
      patients satisfy this normality condition. METHOD AND MATERIALS: 285 treatment
      planning CT and daily CT-on-rails scans from 7 prostatectomy patients were used
      in this study. Both bladder and rectum were contoured on all scans. Each
      patient's daily CT-on-rails scans were registered to his treatment planning CT
      and the bladder/rectum contours were mapped into treatment planning CT space for
      analysis. A cubic box with orientations along treatment planning CT image axes is
      defined to contain all bladders/rectums with 2cm margin. For each voxel inside
      this box (size: 2mm*2mm*1.5mm), its distance to the bladder/rectum surfaces was
      measured. Sign is added to the distance to indicate whether a point is inside or
      outside of an organ of interest. Now the inter-fraction motion/deformation of
      bladder/rectum can be characterized by the distance variation from the voxels to
      the bladder/rectum surface. Jarque-Bera normality statistical test was employed
      to examine whether the signed distances obey normal distribution. RESULTS: For
      each patient, the signed distance to bladder or rectum from at least 99.99% of
      the voxels passed the Jarque-Bera test with p-value 0.05. CONCLUSIONS: For
      prostatectomy patients, their bladder or rectum inter-fraction organ
      motion/deformation can be statistically described by a Gaussian signed distance
      field. This makes it possible to use Bayesian statistics model with Normal-gamma
      conjugate prior to predict bladder or rectum daily location and shape during a
      prostatectomy patient fractionated radiotherapy.

PMID- 28517410
TI  - SU-C-218-06: Evaluation of a CT-Based, Semi-Automated Lung Mass Estimation Method
      Under Varying Acquisition Conditions.
AB  - PURPOSE: To evaluate a simple, semi-automated lung mass estimation method on CT
      scans from a variety of acquisition techniques for mass correction of MIRD dose
      estimates. METHODS: CT scans from ten patients undergoing stereotactic body
      radiation therapy treatment planning on a GE DST PET/CT scanner were analyzed
      retrospectively. For each patient, free- breathing (FB) and respiratory gated 4D
      CT scans were acquired. 4D-CT scans were reconstructed and sorted into ten phases
      representing one complete respiratory cycle. An average CT (ACT) was derived from
      the ten phase reconstructions. Half the patients also had breath-hold (BH) scans.
      Scans were analyzed using Osirix MD's V 1.3 (Pixmeo, Geneva Switzerland) Grow
      Region segmentation tool. Lung volume; average lung, tissue (~lcm ROI in the
      descending aorta), and air (~1 cm ROI in the trachea) HU's were recorded for each
      acquisition type. Lung mass was calculated by assuming each voxel is a linear
      combination of only air and tissue. The fraction of total lung volume consisting
      of lung tissue is assumed to be (lung HU - air HU) / (tissue HU - air HU), and
      mass = total volume X fraction X 1 g/cm3 . RESULTS: 4D-CT mass estimates showed
      variability, with a minimum at end-expiration and a maximum just after end
      inspiration. ACT generally produced the highest estimate. FB and BH estimates
      were near the median. CONCLUSIONS: Although calculated mass increased with
      increasing total lung volume, the difference between minimum and maximum
      population means in the 4D-CT data was 5.5%. FB and BH estimates fell within that
      5.5%, while the ACT mean was 9.8% above the global mean. The range of estimated
      masses (524 g to 977 g) suggests the value of lung mass estimates for more
      patient-specific MIRD dose assessment. Excluding ACT, the results indicate that
      any of the acquisition techniques can provide a reasonable lung mass estimate.
      This work was supported in part by a residency grant from the AAPM.

PMID- 28517411
TI  - SU-D-217BCD-03: Impact of Jaw Width on the Megavoltage Computed Tomography Image
      Quality and Imaging Dose with Helical Tomotherapy.
AB  - PURPOSE: On-treatment megavoltage computed tomography on Helical Tomotherapy
      (Accuray Inc., Sunnyvale, CA) is critical for image guided radiotherapy. A
      strategy was developed to assess the impact of various jaw widths on image
      quality and imaging dose with Tomotherapy. METHODS: A cheese phantom (Gammex RMI,
      Middleton, WI) made of water equivalent materials was employed in this study.
      Three sets of measurements were independently carried out. Firstly, in the
      imaging dose measurement, the phantom was placed on the couch and aligned with a
      stationary green laser and beam isocenter. The measurement point was 10 mm up
      from the cente of the phantom. Three slices on either side of the middle slice
      were selected. Secondly, two inserts with different rows of holes of various
      sizes were placed inside the phantom for image contrast and resolution
      investigation. Lastly, twelve density inserts were placed into the outer holes in
      the phantom for measurement of the image value to density table (IVDT). A
      comparison of imaging dose, image resolution and contrast, IVDT table between
      different jaw configurations was performed to evaluate the imaging system.
      RESULTS: Imaging dose was 2.93 cGy with a jaw size of one mm as opposed to 1.62
      cGy with a four mm jaw, both of which are below the vendor's requirement: 3 cGy.
      However, image quality is improved significantly with the smaller jaw. Four lines
      of holes can be readily identified on images using smaller jaw while only three
      lines visible with the larger jaw. Image contrast is similarly enhanced when
      reducing the jaw size. On average CT numbers are 6% higher with the smaller jaw
      than those obtained with the larger one. CONCLUSIONS: Significant improvement in
      image quality is achieved with the smaller jaw field in Tomotherapy while the
      imaging dose is kept at a clinically acceptable level.

PMID- 28517412
TI  - SU-D-213AB-05: Commissioning a CT Compatible LDR T&O Applicator Using Analytical
      Calculation with ID and 3D Dosimetry.
AB  - PURPOSE: To determine the characteristics of a new commercially available CT
      compatible LDR Tandem and Ovoid (T&O) applicator using 3D dosimetry. METHODS: We
      characterized source attenuation through the asymmetric gold shielding in the
      buckets by measuring dose with diode and 3D dosimetry and compared to an
      analytical line integral calculation. For 3D dosimetry, a cylindrical PRESAGE
      dosimeter (9.5cm diameter, 9.2cm height) with a central 6mm channel bored for
      source placement was scanned with the Duke Large field of view Optical CT-Scanner
      (DLOS) before and after delivering a nominal 7.7Gy at a distance of 1 cm using a
      Cs-137 source loaded in the bucket. The optical CT scan time lasted approximately
      15 minutes during which 720 projections were acquired at 0.5 degrees  increments,
      anda 3D dose distribution was reconstructed with a 0.5mm3 isotropic voxel size.
      The 3D dose distribution was applied to a CT-based T&O implant to determine
      effect of ovoid shielding on the dose delivered to ICRU 38 Point A as well as
      D2cc of the bladder, rectum, bowel, and sigmoid. RESULTS: Dose transmission
      through the gold shielding at a radial distance of 1-3cm from midplane of the
      source was 86.6%, 86.1, and 87.0% for analytical calculation, diode, and 3D
      dosimetry, respectively. For the gold shielding of the bucket, dose transmission
      calculated using the 3D dosimetrymeasurement was found to be lowest at oblique
      angles from the bucket witha minimum of ~51%. For the patient case, attenuation
      from the buckets leadto a decrease in average Point A dose of ~4% and decrease in
      D2cc to bladder, rectum, sigmoid, and bowel of 2%, 15%, 2%, and 7%, respectively.
      CONCLUSIONS: The measured 3D dose distribution provided unique insight to the
      dosimetry and shielding characteristics of the investigated applicator, the
      technique for which can be applied to commissioning of other brachytherapy
      applicators. John Adamovics is the owner of Heuris Pharma LLC. Partially
      supported by NIH Grant R01 CA100835-01.

PMID- 28517413
TI  - SU-D-BRB-04: FDG-PET Histogram Distances: Novel Predictors of Tumor Response to
      Chemoradiotherapy.
AB  - PURPOSE: To examine the accuracy of FGD-PET histogram distances as predictors of
      pathologic tumor response to chemo-radiotherapy (CRT) in esophageal cancer.
      METHODS: Twenty patients were included. A rigid registration was used to align
      the post-CRT PET/CT with the pre-CRT PET/CT images. The primary tumor was
      delineated using a region-growing algorithm with a threshold of SUV = 2.5 on the
      pre-CRT PET. Two histograms of SUVs within the tumor were constructed on the pre
      CRT PET and registered post-CRT PET, respectively. The differences between the
      two histograms reflected changes in the SUV distribution and were therefore
      potential predictors of tumor response. The differences were quantitatively
      measured by histogram distances using 12 bin-to-bin and 8 cross-bin algorithms.
      The accuracy of histogram distances in predicting pathologic tumor response to
      CRT was measured using the area under ROC curve (AUC), prediction accuracy, and
      the Mann-Whitney tests, in comparison with traditional PET response measures and
      texture features. RESULTS: Cross-bin histogram distances were shown to be
      significant (p<0.05) predictors of pathologic tumor response. They were more
      accurate than bin- to-bin histogram distances (not significant). The most
      accurate cross-bin histogram distances were: Quadratic-Chi distance (AUC=0.89,
      accuracy=80%, p=0.003), Earth Mover distance (AUC=0.83,accuracy=80%, p=0.014),
      diffusion distance (AUC = 0.82, accuracy=85%, p=0.02) and Match distance (AUC =
      0.79, accuracy=80%, p=0.03). This family of novel predictors were more accurate
      than traditional PET response measures using SUVmax (AUC=0.76, accuracy=75%,
      p=0.05), SUVpeak (AUC=0.74, accuracy=70%, p=0.08), Total Glycolytic Volume
      (AUC=0.76, accuracy=70%, p=0.05), as well as texture features based on the
      cooccurrence matrix (Inertia: AUC=0.85, accuracy=80%, p=0.01). CONCLUSIONS: The
      cross-bin histogram distances characterized changes in the SUV distribution
      within a tumor and showed high accuracy for the prediction of pathologic response
      to CRT in esophageal cancer. This workwas supported in part by the National
      Cancer Institute Grant R21 CA131979.

PMID- 28517414
TI  - SU-D-213CD-02: The Accuracy of AlignRT Guided Set-Up for Whole Breast and
      Chestwall Irradiation.
AB  - PURPOSE: To evaluate the ability of AlignRT (VisionRT Ltd., London, UK) to
      accurately position patients receiving whole breast or chestwall irradiation and
      the impact of AlignRT on portal image dose. METHODS AND MATERIALS: Twenty whole
      breast or chestwall cases set-up using AlignRT at our site were compared to a
      series of 20 similar patients set-up without the use of AlignRT over the same
      time span. All patients were set-up head first supine, on a Quest Breastboard
      (Qfix, Avondale,PA). The AlignRT patients were positioned with an AlignRT region
      of interest that encompassed the ipsa-lateral chest minus the breast tissue drawn
      on a surface created from the patient contour generated in treatment planning.
      Non-AlignRT patients were positioned using skin marks added in simulation.
      Positional accuracy was verified by qualitative evaluation of portal imaging on
      the first treatment day, then once weekly. RESULTS: The percentage of port images
      that were deemed unacceptable by therapists or radiation oncologists (> 3 mm
      deviation from simulation position) was 7.5 +/- 8.1% for the AlignRT group (with
      a range of 0 - 15%). In 14 of the 20 cases, one or fewer port images were
      unacceptable over the entire treatment. For the non-AlignRT group 20 +/- 14% (0
      45%) of the images were unacceptable. In only 6 of the 20 cases one or fewer port
      images were found to be unacceptable over the course of treatment. CONCLUSION: As
      judged by port images, AlignRT is able to provide a more accurate positioning of
      whole breast and chestwall patients, with a reduction in port dose and in set-up
      time, compared to the use of lasers and skin marks. The reduced number of
      rejected port images strongly suggests that AlignRT gives a more consistent,
      reproducible set-up on non- port days than skin marks alone.

PMID- 28517415
TI  - SU-D-211-04: Sector Intensity Modulated (SIM) Gamma Knife Stereotactic
      Radiosurgery.
AB  - PURPOSE: The latest Gamma Knife (GK) system, Perfexion, consists of 192 Co-60
      sources divided into eight sectors. Treatment delivery includes multiple shots
      placed at different positions. For every shot, each sector can be either blocked
      or open with four different aperture sizes. However, the beam-on time is designed
      to be fixed. We proposed an innovative concept, Sector Intensity Modulated (SIM)
      Gamma Knife by dynamically varying the beam-on time for each individual sector to
      improve stereotactic radiosurgery planning quality. METHODS: The anatomic
      structures and dose matrices from each sector for every shot were obtained from
      the GK workstation. The beam-on time for each sector was decomposed with various
      discrete levels and brute-force algorithm was used to get the optimal solution.
      The resulting SIM plan was then re-entered into the GK workstation. Six indices
      were used to benchmark the plan quality: Coverage, Conformality, Gradient,
      Maximum Dose(s) to critical structure(s), Volume receiving over 8 and 12 Gy. All
      the SIM plans in comparison with the original plans were further reviewed by an
      experienced oncologist. RESULTS: The simulations were tested on various pituitary
      adenoma cases. Results consistently showed that SIM yielded better plans with all
      quantitative indices improved compared to original plan. It provides better
      conformality, quicker drop off of the isodose line outside the tumor, lower doses
      to the critical structures as optical- nerve/chiasm while maintaining at least
      99% coverage of the tumor. Results were more favorable according to oncologist's
      view. In particular, up to 20% or 0.6 cc volume decrease in healthy tissue
      receiving 8 Gy was observed. This may translate into clinically observable
      reduction in acute/late toxicities. CONCLUSIONS: Our preliminary results show
      that Sector Intensity Modulated Gamma Knife offers superior treatment plans
      compared to the originally delivered plans. Further works as adding dynamic shot
      location and dynamic shot shaping will be discussed.

PMID- 28517416
TI  - SU-D-217A-01: A High-Resolution in Vivo Molecular Imaging Technique Based on X-
      Ray Fluorescence.
AB  - PURPOSE: Traditional molecular imaging techniques such as PET/SPECT have many
      limitations, including relatively low spatial resolution, short lifetime of
      radioisotope probes, limited availability due to reliance on cyclotron,
      relatively high dose, and lack of effective molecular probes for certain tumor
      cells. In this work we demonstrate the feasibility of a novel x- ray fluorescence
      molecular imaging (XFMI) technique using high-power carbon nanotube (CNT) x-ray
      array technology. The XFMI overcomes some limitations and will be a significant
      advance in molecular imaging technology for cancer drug development and cancer
      biology research. METHODS: A testing chamber was constructed containing two
      Amptek energy-resolving detectors analyzing a copper collimated fluorescence beam
      placed opposite each other symmetric about the sample and perpendicular to the
      primary incoming x-ray beam, also using the copper collimator. Different
      concentrations of indium trichloride and iodine were tested to determine the
      minimum detectable concentration (MDC) for each. RESULTS: The MDC for indium was
      found to be 80 ug/mL and 100 ug/mL for iodine at 50 kVp, 30mAs (5 minutes imaging
      time). This is on the order of magnitude of the MDCs determined at large
      synchrotron facilities using XFI. Higher concentrations above 1mg/mL of both
      elements were detectable at 1.5 mAs (15 seconds). CONCLUSIONS: These results show
      that it is possible to not only measure low concentrations of the above elements,
      but also distinguish between similar L-alpha peaks. This allows for future work
      of obtaining 2D and 3D imaging to determine element types and concentrations
      diffused in different parts of the body. Carolina Center of Cancer
      Nanotechnology, University Cancer Research Fund.

PMID- 28517417
TI  - SU-D-BRCD-03: Spectroscopic Characterization of a 6 MV Linear Accelerator Field
      Using Compton Spectrometry Measurements and Monte Carlo Techniques.
AB  - PURPOSE: Effective treatment planning for radiotherapy is dependent on accurate
      spectra determination; however, direct measurements of spectra arecomplicated by
      fluence rates that exceed detection system limitations. This work demonstrates
      the potential to use a Compton scattering technique to measure the spectrum of a
      6MV linac. These spectra are further characterized using Monte Carlo (MC)
      simulations. METHODS: A high-purity germanium detector was used to measure the
      photon spectrum scattered at35 degrees from the central axis of 3cmx3cm and
      lOcmxlOcm 6MV fields from a Varian linac. Photons were scattered using aluminum
      rods positioned at isocenter, and were admitted to the detector through a 30cm
      long collimating aperture. The measured Compton-scattered spectra were corrected
      for background. An MC model of the linac was developed in MCNP5 to calculate
      central- and off-axis spectra. The model geometry was verified by comparisons
      with percentage depth-dose and profilemeasurements. The spectroscopic effect of
      the mean energy, radius, and divergence of the electron beam incident on the
      target was tested for twofield sizes. RESULTS: The count rate of the scattered
      beam increased with field size and scattering rod diameter. Preliminary
      measurements indicate that the spectrum was shifted to lower energies using this
      technique; however, the signal-to-noise ratio was poor due to leakage and room
      scatter. MC simulations demonstrate that the central- and off-axis spectra were
      sensitive to changes in mean electron energy; however, changes in beam diameter
      and angular divergence did not substantially affect either the central- or off
      axis spectra. CONCLUSIONS: This work demonstrates that the spectrum from a 6MV
      linac can be measured using Compton spectrometry. Further work is required to
      increase the signal-to-noise ratio and correct fordetector response. MC
      simulations indicate that the spectra were sensitive to variations in the
      parameters used to define the primary electron beam incident on the target.

PMID- 28517418
TI  - SU-D-217A-04: Evaluation of the Spatial Concordance Between the Intratumoral
      Patterns of 18F-FLT and 18F-FDG Uptake in a Small Animal Tumor Model.
AB  - PURPOSE: PET imaging allows for the visualization of tumor microenvironment and
      identification of aggressive or radioresistant tumor subvolumes that can be
      targeted with an escalated radiation dose. Multiple PET tracers have been
      developed for visualization of different aspects of tumor microenvironment;
      however, the spatial distribution of tracers in tumors is equally affected by
      tumor tissue viability and tracer delivery limitations. Given these issues and
      the low resolution associated with PET imaging, two different PET tracers can
      produce very similar images. Therefore, it is important to demonstrate that a
      novel PET tracer does provide additional useful information to that obtained with
      other tracers. This study investigates the added value of performing 18F-FLT PET
      imaging as well as 18F-FDG imaging. METHODS: Head and neck tumor xenografts grown
      in nude mice were used to study intratumoral tracerdistributions. 18F-FDG and 18F
      FLT PET images were obtained on subsequent days using a small animal PET/CT.
      Pinnacle 9 was used to deformably register the CT image from the FLT PET/CT to
      the FDG PET/CT image set. The generated deformation was applied to the FLT PET
      image to achieve an unbiased FLT to FDG PET image registration. The Pearson
      correlation coefficient between FDG and FLT was calculated voxel- by-voxel within
      a tumor contour. Overlap analysis of thresholded tracer distributions was carried
      out by comparing Dice similarity coefficients. RESULTS: Both SQ20B and FaDu
      tumors showed a moderate voxel-by-voxel correlation between FDG and FLT
      intratumoral patterns of uptake with an average rho value of .56 and .63
      respectively (range .37-.76) despite significant differences in tumor morphology.
      The average volumes under thedice coefficient surface for SQ20B and FaDu tumors
      were not significantly different. CONCLUSIONS: Despite being equally affected by
      the issues of tracer delivery, necrosis and PET resolution, FDG and FLT PET
      images displayed an observable difference at clinically relevant thresholds.

PMID- 28517419
TI  - SU-E-E-03: Ethics and Professionalism Education in Medical Physics: A Needs
      Assessment Study.
AB  - PURPOSE: To perform a needs assessment survey of ethics/professionalism education
      in medical physics and ethical/professional challenges in clinical,research and
      educational settings with the intent of supplementing and customizing TG159
      recommended ethics curriculum for medical physics trainees. METHODS: A web-based
      survey was conducted among AAPM members to assess current practices, attitudes
      and perceptions pertaining to ethics/professionalism education and
      ethical/professional misconduct or questionable behavior and practices in the
      field. RESULTS: The survey was distributed by AAPM to 7708 members via email;
      1362 (17.7%) responded. Seventy-five percent of the respondents were male. Sixty
      percent (805/1345) stated they received no education in ethics/professionalism.
      Eighty-one percent (126/155) of current trainees received instruction in
      ethics/professionalism, as opposed to 35% (392/1130) of those who are post
      training. There was strong support (>90%) for continuing education in
      ethics/professionalism; seventy-five percent (1019/1354) supported sessions on
      ethics and professionalism at national meetings. Most preferred method of ethics
      instruction was periodic discussion sessions involving faculty and trainees, with
      the least interest expressed for a separate course. Many reported direct personal
      knowledge of one or more instances of a variety of professional/ethical
      misconduct or questionable behavior. Thirty eight percent (458/1192) reported
      poor mentorship, with women reporting this concern more often than men
      (129/281,46% versus 316/877, 36%, p<.05). Over one-fourth of respondents reported
      being asked to perform low educational value tasks and expressed concerns about
      fairness. A significant minority also reported questionable behavior with respect
      to authorship assignment (346/920, 38%), data fabrication (107/924, 12%), data
      falsification (94/919, 10%); concerns about research subject privacy and
      confidentiality were lower (64/887, 7%). CONCLUSIONS: Data gathered through the
      survey is guiding our efforts to develop a case-based ethics curriculum and
      instructional materials for medical physics trainees at our institution. This
      effort may be useful to other medical physics programs which offer ethics
      training/education. This work has been funded in part by a grant from the
      National Institutes of Health, T32 EB002103-22S1.

PMID- 28517420
TI  - SU-D-211-06: The Effect of Motion in RapidArc Lung SBRT Delivery.
AB  - PURPOSE: RapidArc is routinely used for stereotactic radiotherapy for lung
      cancer. While treatment dose is optimized and calculated on a static CT image,
      the motion of the target in conjunction with the motion of the MLC may Result in
      a delivered dose deviating from the planed dose. In this study, we investigate
      the dosimetric consequences of the inter-play effect by simulating dynamic dose
      delivery on a dynamic CT dataset of real patients. METHODS: The target motion in
      20 patients was analyzed and 5 patients with >10 mm motion were chosen for this
      study. The RapidArc plan for eachpatient is optimized on a free-breathing CT
      using 2 arcs. Inherent in each plan is data on the associated parameters such as
      timestamp, MLC leave position, gantry angle and delivered beam MUs for each
      control point. Simulated dynamic delivery is performed by associating these
      parameters with each of the breathing phases of the 4D-CT. The starting breathing
      phase is selected randomly for each of the two arcs. Dose from the derived
      partial plans associated with each phase of the 4D-CT dose is recalculated in
      Eclipse. Accumulation of dose is performed using deformable image registration
      from each phase of the 4D-CT to the exhale phase of the 4D-CT. RESULTS: The
      coverage of the GTV and PTV shows negligible variations from the interplay
      effect. But the Homogeneity Index is affected by the motion. The prescription
      isodose volume is smaller than what was from the treatment plan dose. There were
      both intra- and inter-fraction effects seen inthe OARs dose in some patients.
      CONCLUSIONS: We investigated the motioneffect in RapidArc Lung SBRT delivery in 5
      patients. Negligible variations were shown for target coverage. However the
      motion effects were observed in high dose distribution and volume. Some OARs dose
      distributions were affected by the motion.

PMID- 28517421
TI  - SU-D-218-02: 4D-MRI Based on Body Area (BA) Surrogate and Sagittal Image
      Acquisition.
AB  - PURPOSE: 4D-MRI based on body area (BA) surrogate using axial image acquisition
      has been demonstrated. Since respiratory motion mostly occurs in the superior
      inferior (SI) direction, it is expected that sagittal acquisition may provide
      more robust and accurate breathing signal than axial acquisition. The aim of this
      study was to investigate the feasibility of extracting breathing signals from
      sagittal images using BA surrogate and its application in 4D-MRI. METHODS: 7
      human subjects were imaged continuously in a single (n=5) or multiple (n=2)
      sagittal planes using a steady-state precession sequence. Imaging parameters
      were: TR/TE, 3.7ms/1.21ms; Matrix, 256*166; FOV, 350*300mm; flip angle, 52
      degrees ; slice thickness, 5mm; frame rate: ~3 frames/s. Imaging time per slice
      is 2 minutes for single slice acquisition and ~10 seconds for multi-slice
      acquisition. Breathing signals were generated for all subjects by tracking the
      change of BA. The multi-slice sagittal acquisition was performed on a MRI-
      compatible motion phantom with a cylindrical gel target and was simulated on a 4D
      digital human phantom. Breathing signals were extracted from the sagittal images
      using the BA surrogate. Respiratory phases were calculated. 4D-MRI of both
      phantoms were retrospectively reconstructed based on the respiratory phases.
      RESULTS: Breathing signals extracted from both single slice and multi-slice
      sagittal acquisitions showed stable and well- characterized patterns. 4D-MRI of
      the physical phantom showed clear sinusoidal motion of the gel target in all
      three planes with minimal artifacts. Simulated '4D-MRI' of the 4D digital phantom
      matched well with original images: the mean absolute difference in motion
      amplitude of the 'tumor' was 0.4+/-0.3mm. Small artifacts of discontinuity were
      observed in the SI direction in certain phases. CONCLUSIONS: It is feasible to
      extract breathing signals from sagittal images for 4D-MRI application. Further
      investigation is needed to test whether sagittal acquisition is more robust and
      accurate than axial acquisition for breathing signal extraction.

PMID- 28517422
TI  - SU-D-BRCD-05: Evaluation of New Exit Detector Based Transit Dosimetry Software
      for TomoTherapy Treatments.
AB  - PURPOSE: The prospect of 3D transit dosimetry to verify treatment delivery is a
      novel and emerging technology in TomoTherapy. Math Resolutions, LLC, has expanded
      their Dosimetry Check (DC) quality control software to include transit dosimetry
      calculations for TomoTherapy treatments. The data recorded by the MVCT detectors
      during patient treatment is used in conjunction with the planning CT to calculate
      the delivered dose to the patient from each fraction. This study presents a
      summation of our experiences at the University of Virginia in collaboration with
      Math Resolutions in verifying and implementing the transit-dose calculation
      aspects of this new TomoTherapy specific product. METHODS: Low and high
      modulation cheese phantom plans and clinical plans (prostate, GYN, pituitary, and
      thoracic vertebra) were used to evaluate the DC transit dosimetry software. The
      TomoTherapy planning CT, structure set, plan, and dose for each plan were
      imported into the DC software. The fluence maps were reconstructed from the exit
      detector data by correcting for patient attenuation and used to compute the
      delivered dose. The resulting dose distribution is compared with the TPS planned
      dose using isodose line comparison and gamma index. RESULTS: The percent
      difference between the planned and DC calculated doses ranged between 0.63% for a
      low modulation cheese phantom plan to 5.94% for a prostate plan. Using criteria
      of 3%, 3mm, the gamma index passing rate for the tested plans ranged from 94.7%
      to 99.1% <1 for the overall patient area and from 88% to 96.4% for the treatment
      area receiving at least 80% of the prescribed dose. CONCLUSIONS: The results from
      our evaluation of Math Resolutions' DC look promising and generally within an
      acceptable range for portal dosimetry programs. Further investigations will
      include developments to improve the DC algorithm and determine how it can best be
      implemented in a typical TomoTherapy clinical workflow. Research Grant from Math
      Resolutions LLC 01/12/2012-01/11/2013 Math ResolutionsTM Dosimetry Checksoftware
      was given to UVa to assist with evaluating the precision of the product in
      reconstructing dose from the TomoTherapy exit detector data.

PMID- 28517423
TI  - SU-D-BRA-04: Improvement of Diaphragm Motion Reproducibility in MRI Using
      Audiovisual Biofeedback for Lung Cancer Radiotherapy.
AB  - PURPOSE: Previous studies have investigated the effect of AV biofeedback on the
      external respiratory signal reproducibility. This is the first study
      investigating the effect of AV biofeedback to improve the motion reproducibility
      of the internal anatomy. The aim of the project is to test the hypothesis that AV
      biofeedback improves the diaphragm motion reproducibility. METHODS: An AV
      biofeedback system has been employed with MRI acquisitions. The AV biofeedback
      system utilized (1) the external marker position on the abdomen using an RPM
      system (Real-time Position Management, Varian) to audio-visually guide a human
      subject for regular breathing and (2) a fast Gradient-Recalled-Echo (fGRE) MR
      pulse sequence of 3 Tesla GE MRI (GE Healthcare) to monitor the diaphragm motion
      (200ms). The improvement in the diaphragm motion reproducibility using the AV
      biofeedback system combined with MRI has been assessed in 26 studies with 13
      healthy human subjects. Each subject underwent two studies for assessment of the
      diaphragm motion reproducibility both with AV biofeedback and without (free
      breathing). The second study features a reversed order of breathing conditions.
      The total MRI acquisitions across the 26 studies are 202 measurements including
      sagittal and coronal planes. RESULTS: Average RMSE (root mean square error) of
      diaphragm displacement obtained from MRI analysis has been reduced from 2.7mm of
      free breathing to 1.6mm of AV biofeedback breathing (p-value < 0.05).
      Additionally, the average RMSE of diaphragm motion period was reduced from 1.84s
      with free breathing to 0.34s with AV biofeedback breathing (p- value < 0.05). 22%
      of average displacement error was reduced using AV biofeedback in the first
      study, and 47% reduction in the second study. CONCLUSIONS: The study demonstrated
      the improvement in the diaphragm motion reproducibility using AV biofeedback.
      This system can provide clinically applicable motion management of the internal
      anatomy in MRI and for Image Guided Radiotherapy (IGRT).

PMID- 28517424
TI  - SU-D-217BCD-02: Online Angular Tube Current Modulation in X-Ray Computed
      Tomography: Can Tube Current Be Modulated Appropriately?
AB  - PURPOSE: In X-ray computed tomography (CT), X-rays are significantly less
      attenuated in the anteroposterior direction and more in the lateral direction.
      Therefore, the tube current should be adjusted within one gantry rotation using
      angular tube current modulation (TCM). The aim of this study was to evaluate
      whether online angular TCM could reduce radiation dose appropriately. METHODS: A
      128-detector dual-source CT (SOMATOM Definition Flash; Siemens Healthcare,
      Erlangen, Germany) and an online TCM system (CARE Dose 4D; Siemens Healthcare)
      were used. Dose profiles were acquired using the CT Dose Profiler (RTI
      Electronics, Molndal, Sweden) and an elliptical cylindrical phantom (MHT; Kyoto
      Kagaku, Kyoto, Japan) for helical CT scans with and without TCM. In addition,
      absorbed dose distributions within a single section were acquired using an
      anthropomorphic phantom (RANI 10; The Phantom Laboratory, Salem, NY) and
      radiophotoluminescent glass dosimeters (RPLDs) (GD- 302M; Chiyoda Technol, Tokyo,
      Japan) for helical CT scans with and without TCM after placing RPLDs within all
      holes of one section and pasting them around the section. A graph of each
      absorbed dose distribution was drawn using graphing software (ORIGIN 8.6;
      OriginLab, Northampton, MA). RESULTS: The acquired dose profiles suggested that
      online angular TCM could adjust the tube current in near-real time according to
      the attenuation measured from the previous projection. The profiles gradually
      stabilized because the tube current was adjusted properly. The absorbed doses
      were low and the distributions were stable with TCM compared with those without
      TCM. CONCLUSIONS: In X-ray CT, an online angular TCM can reduce radiation dose
      effectively by adjusting tube current within one gantry rotation in near-real
      time.

PMID- 28517425
TI  - SU-D-213AB-04: Evaluation of the Dose Calculation in a Commercial Planning System
      for a Breast Cancer Brachytherapy Technology Using Monte Carlo Simulation.
AB  - PURPOSE: To evaluate the dose calculation in a commercial treatment planning
      system (TPS) for a breast cancer brachytherapy technology using Monte Carlo
      simulation for 21 patients. METHODS: Plans for 21 patients who received SAVI
      treatments were modeled using data from the TPS including CT images, structures
      and source information. The MC code PENELOPE was used, inputting images in voxel
      format, where density and material (tissue, air, bone and Nitinol) for each voxel
      were assigned based on its calibrated Hounsfield units and contoured structure
      sets, respectively. For the source model only gamma-rays and fluorescence X-rays
      of the NuDat database 192Ir spectrum were used, leaving out photons with emission
      intensity less than 0.1% and X-rays with energies below 10 keV. Source positions
      were entered into the plan and run individually. Dose was totaledby individually
      weighting the dose for each source position using the original TPS plan dwell
      times and then summing the weighted dose for all positions. RESULTS: Dose from
      the Monte Carlo plan was compared with dose from the original plan using isodose
      lines at 50, 100, 150 and 200% of the prescription dose of 34Gy. Dosimetric
      coverage of the target was compared by evaluating the V100, V150 and V200 (volume
      of the target covered by 100%, 150 and 200% of the dose respectively). The V200
      and V150 had an average increase (and standard deviation) of 9.1% (3.2%) and 3.8%
      (1.4%) respectively, while the average change in V100 was 1.2% (1.0%). Where
      variance for the entire simulation was 0.9%. CONCLUSION: We have compared dose
      distributions of a commercial TPS using Monte Carlo simulation for SAVI breast
      cancer brachytherapy and found that a dose increase near the air-tissue
      interface.

PMID- 28517426
TI  - SU-D-218-06: Acceleration of Optical Photon Monte Carlo Simulations Using the
      Macro Monte Carlo Method.
AB  - PURPOSE: The purpose of this work is to demonstrate that optical photon Monte
      Carlo simulations via a photon transport code called MCML can be accelerated
      using macro Monte Carlo (MMC) techniques. METHODS: MCML was modified to
      incorporate the macro Monte Carlo radiation transport method. The original MCML
      uses scattering, absorption, reflection and refraction physics to transport
      optical photons through multi-layered geometries. The code determines
      transmission, reflection and absorption for the layered geometry specified by the
      user. To make the code run faster, the MMC version of MCML uses large, multi
      interaction steps in regions that are homogeneous. These large steps are pre
      computed and stored in a database with many step sizes, materials and photon
      energies. The MMC version of MCML determines whether large MMC steps or
      traditional Monte Carlo should be used depending on the photon's current location
      inthe geometry. RESULTS: The MMC version of MCML was tested against the original
      MCML code for a number of simple test geometries. It was also tested in
      anatomical geometries that are often uses in optical photon modeling. This
      includes skin and skull geometries. In each case, the reflection and transmission
      results from each code differed by less than 0.5%. The absorption data produced
      by each code also differed by less than 0.5% in most cases, and never differed by
      more than 2%. The MMC version of MCML runs between 1-3 times as many particles
      per unit time comparedto MCML, depending on the geometry. CONCLUSIONS: Applying
      Macro Monte Carlo methods to MCML produces a faster code without compromising
      accuracy. The speed-gains are greatest in geometries thathave regions that are
      large relative to the mean scattering length for photons in that region. This
      work has the potential to accelerate light modeling for both photodynamic therapy
      and near-infrared spectroscopic imaging.

PMID- 28517427
TI  - SU-D-BRB-03: Prediction of Tumor Outcomes Through Wavelet Image Fusion and
      Texture Analysis of PET/MR Imaging.
AB  - PURPOSE: To investigate the combination of PET/MR image features for the early
      prediction of tumor metastases to the lungs in soft-tissue sarcoma (STS) cancer.
      METHODS: A dataset of 24 patients with histologically proven STS was used in this
      study. All patients underwent pre-treatment FDG-PET and MR scans, which comprised
      of T1 and T2-fat suppression weighted (T2FS) sequences. The patients had a median
      follow-up period of 36 months (range: 6-69 months). Eight patients developed
      metastases to the lungs.Tumors were contoured on the T2FS scans by an expert
      physician. Fusion of the co-registered FDG-PET/MR scans was performed using a
      wavelet transform technique. A SUV feature (SUVmax) from the FDG-PET scans and 6
      texture features from the co-occurrence matrix of the fused scans were extracted
      from the tumor region and correlation with the clinical endpoint of metastases to
      the lungs was investigated. Statistical analysis was performed using Spearman's
      rank correlation (rs) and multivariable logistic regression. RESULTS: The highest
      univariate prediction was found on FDG-PET/T2FS fused scans analyzed using the
      texture features "Sum-Mean" and "Variance". These two fused scan-texture feature
      combinations reached rs = -0.6838 (p = 0.0003). In comparison, SUVmax reached rs
      = -0.6257 (p = 0.0011). The highest multivariate prediction was found with the
      following 3- parameter model: -3.15*SUVmax - 5.37*FDG-PET/T2FS-Sum-Mean +
      0.57*FDG-PET/T1-Variance. This model reached rs = 0.7977 (p = 0.000005).
      CONCLUSIONS: This work indicates the potential of PET/MR texture features of
      tumors as complementary metrics to existing prognostic factors. Substantial
      improvement in terms of prediction of metastases to the lungs in STS cancer was
      found with the combination of texture features from fused FDG-PET/MR scans.
      Potentially, this could improve patients' outcomes by allowing better adaptation
      of treatments. Future work will involve evaluation of the robustness of the
      proposed method and validation on a larger set of patients.

PMID- 28517428
TI  - SU-D-211-03: An Automated Inverse Planning Optimization Approach for Single-
      Fraction and Fractionated Radiosurgery Using Gamma Knife Perfexion.
AB  - PURPOSE: The purpose of this work is to develop an automated inverse planning
      approach to generate singe-fraction and fractionated stereotactic radiosurgery
      (SRS) treatment plans for Gamma Knife Perfexion. METHODS: Our automated approach
      consists of two steps: 1) a grassfire-based algorithm to carefully determine the
      isocentre locations; 2) a penalty-based optimization to find the optimal shot
      shapes and their intensities to minimize the deviation of the delivered dose from
      the objective dose in all structures. For single-fraction SRS, a margin-less
      approach was taken: conformity of dose to the gross tumor volume (GTV) with a
      steep dose fall-off was prioritized. For fractionated radiosurgery, dose
      homogeneity was given a higher priority since planning target volumes (PTV) were
      applied to account for daily setup variation, and these PTVs could overlap with
      organs-at-risk (OARs). The two-step approach was tested on seven clinical cases
      with PTV sizes of 0.5cm3-56.5cm3. In the tested cases, the PTV had 0%-38% overlap
      with OARs. RESULTS: For single-fraction SRS, the dose to 1mm3 brainstem was on
      average 0.24Gy (range: -2.4Gy to +2.0Gy) lower compared to manually-generated
      plans. Beam-on time varied with the number of isocentres, but on average was
      33min longer than manually- generated plans. The optimization algorithm took
      215min on average, while isocentre selection performed in <10s.For fractionated
      SRS, the average PTV coverage was V95=94.9% (range: 92.7%-97.6%) and the mean
      dose to 1 mm3 brainstem was 87.8% of the prescription dose (range: 35.4%-
      108.8%). The mean beam-on time per fraction per dose-per-fraction was 4.8min/Gy
      (range: 0.9min/Gy-10.3min/Gy). We observed a tradeoff between conformity and OARs
      sparing in both plans, and added sensitivity to isocentre locations in
      fractionated plans. In all the cases, GTV received the full prescription dose.
      CONCLUSIONS: The results indicated that automated inverse planning yields
      improved conformity and OAR-sparing for single- fraction SRS and is capable of
      generating homogeneous fractionated SRS. This work is partially funded by Elekta
      Instrument, AB, Stockholm, Sweden.

PMID- 28517429
TI  - SU-D-217BCD-06: Evaluation of Effective Dose during Neuro 3-D Imaging Using a C
      Arm Cone-Beam CT System.
AB  - PURPOSE: The purpose of this study was three-fold: 1) to estimate the organ doses
      and effective dose (ED) for patients undergoing neuro 3D-imaging protocols, 2) to
      study the effect of beam collimation on ED, and 3) to derive protocol-specific
      DAP-to-ED conversion factors. METHODS: A cone-beam CT system (Philips Allura Xper
      FD20/20) was used to measure the organ doses for seven neuro imaging protocols.
      Two data sets were obtained: seven protocols with uncollimated beam (FOV: entire
      head) and four with beam collimation (FOV: roughly from the base to the top of
      the skull). Measurements were performed on an adult male anthropomorphic phantom
      (CIRS, Norfolk, VA) with 20 MOSFET detectors (Best Medical Canada, Ottawa,
      Canada) placed in selected organs. The dose area product (DAP) values were
      recorded from console. The ED values were computed by multiplying measured organ
      doses to corresponding ICRP 103 tissue weighting factors. RESULTS: For seven
      protocols with uncollimated setting, the EDs ranged from 0.16 mSv to 1.6 mSv, and
      the DAP-to-ED conversion factors range from 0.037 to 0.17 mSv/Gy/cm2 . For four
      protocols with beam collimation, the ED was reduced approximately by a factor of
      2, and the DAP-to-ED conversion factors by approximately 30%. CONCLUSIONS: We
      have measured ED for standard adult neuro imaging protocols in a 3-D rotational
      angiography system. Our results provide a simple means of ED estimation using DAP
      values from console in the C-arm cone-beam CT system. Research was funded in part
      by Philips Healthcare, the Netherlands.

PMID- 28517430
TI  - SU-D-BRCD-02: A Novel Cylindrical 3D Water Scanner for Beam Data Collection: I.
      Validation of the Automatic-Setup.
AB  - PURPOSE: To determine the accuracy and reproducibility of the automatic- setup
      procedure of a 3D water scanner (3D SCANNER, Sun Nuclear Corp). The procedure
      automatically aligns the scanner's coordinate system to the Linac coordinate
      system. A unique off-center detector holder extends the scan range to 630 mm,
      eliminating the need for scanner shifts for large-field scans. METHODS: The
      automatic-setup procedure provides means to automatically (1) level the tank; (2)
      zero the detector position to water surface; (3) align the scanner's coordinate
      system to the Linac system; and (4) correct motor hysteresis. After automatic
      setup, (1) and (2) were evaluated visually by three physicists. Step (3) was
      tested by moving one of the jaws to the isocenter and scans were made along the
      jaw edge. Angular misalignment between the scanner and the Linac would Result in
      a noticeably tilted profile. Step (4) was tested by scanning with the chamber
      moving forward and then backward five times. The accuracy of the off-center
      detector holder was tested by comparing scans made using the regularand the off
      center detector holders. All tests were repeated three times. RESULTS: All tests
      of the water surface and horizontal chamber movementwere acceptable from the nine
      independent evaluations. Scans along the jawedge resulted in < 1% in profile
      tilt, corresponding to < 0.05 degree in angular misalignment. Same direction
      scans resulted in field edge differences < 0.05 mm, and < 0.2 mm when compared to
      scans in thereverse direction. There was no difference in accuracy when different
      scan speeds were used. Profiles obtained using the regular and the off
      centerdetector holders were identical. CONCLUSIONS: The automatic-setupprocedure
      resulted in accurate alignment of the 3D SCANNER to the Linac. These results were
      user-independent. It also provides the ability to scan large fields without the
      need to change tank setup. This work was partially supported by a research grant
      from Sun Nuclear Corp., Melbourne, FL.

PMID- 28517431
TI  - SU-D-BRA-01: Accurate Real-Time Tumor Motion Estimation from Respiratory
      Surrogates via Memory-Based Learning.
AB  - PURPOSE: Respiratory tumor motion is a major challenge in radiation therapy.
      Effective beam gating or tracking approaches necessitate an accurate knowledge of
      the real-time tumor motion. Fluoroscopic tracking with implanted fiducial markers
      is invasive and exposes the patient to additional imaging dose. Respiratory
      surrogate signal measured by external noninvasive and non-ionizing devices
      provides an attractive approach, in which estimating the tumor motion from
      respiratory surrogates is crucial. METHODS: We utilize a powerful memory-based
      learning approach to find the complex relations between tumor motion and
      respiratory surrogates. The learning method uses locally weighted functions to
      interpolate between and extrapolate from training data. Due to the local nature
      of the learning functions, it is inherently robust to outliers. Moreover, both
      training and adapting to new data is highly efficient and almost free, making it
      suitable for dynamically following possibly variable internal/external relations.
      We evaluated the method using respiratory motion data (3D tumor motion plus 1D
      surrogate) from six patients (three lung and three pancreas patients). RESULTS:
      Given only 5-sec (roughly one breath) pretreatment training data, the method
      achieved an average 3D error of 0.37 mm (range: 0.10 mm - 1.06 mm) and 95th
      percentile error of 0.86 mm (range: 0.24 mm - 2.47 mm) on 120-sec unseen test
      data. These errors are well below the average peak- to-peak amplitude (-10 mm).
      The errors decrease monotonically with an increasing amount of training data.
      Compared with the best linear model, the learning approach achieved a 21%
      reduction in error for an average patient (range: 10% - 42%). CONCLUSIONS: The
      memory-based learning technique is able to accurately capture the highly
      nonlinear and complex relations between tumor and surrogate motion in an
      efficient manner (~1 ms per prediction). These desirable properties make it an
      ideal candidate for accurate and robust tumor gating/tracking using respiratory
      surrogates.

PMID- 28517433
TI  - SU-E-T-441: A Feasibility Study to Replace Electron Cutouts with a Motorized
      Electron Multileaf Collimator.
AB  - PURPOSE: Fabrication of electron beam cutouts not only is a time consuming
      process but also involves the handling of cerrobend which is a toxic material.
      Hospital workers involved in cutout construction can actually be exposed to toxic
      fumes that are usually generated during the process. The aim of this work is to
      study the feasibility of replacing electron cutouts with our prototype motorized
      electron multileaf collimator (eMLC). METHODS: Electron beams collimated by an
      eMLC have very similar penumbra to those collimated by applicators and cutouts as
      we already demonstrated in a previous study. However undulation of the isodose
      curves is expected due to the finite size of the eMLC. This may be a problem when
      the field edge is close to critical structure. Thus ten different breast cases
      that were previously treated with an electron boost were selected from our
      database. An inhouse Monte Carlo based treatment planning system were used for
      dose calculation using the patients CTs. For each patient two plans were
      generated one with electron beams collimated using the applicator/cutout
      combination and the other plan with beams collimated only by the eMLC. Treatment
      plan quality was compared for each patient based on dose distribution and dose
      volume histogram. In order to determine the optimal position of the leaves, the
      impact of the different leaf positioning strategies were investigated. RESULTS:
      Results have shown that target coverage and critical structure sparing can be
      effectively achieved by electron beams collimated by eMLC. Preliminary results
      have shown that the out-of-field strategy is most conservative and would be the
      recommended method to define the actual leaf position for the eMLC defined field.
      CONCLUSION: The eMLC represents an effective time saving and pollution free
      device that can completely eliminate the need for patient specific cutouts. This
      work has been supported by a UICC American Cancer Society Beginning Investigators
      Fellowship funded by the American Cancer Society.

PMID- 28517432
TI  - Newborn screening for PIDs using both TREC and KREC identifies late occurrence of
      B cells.

PMID- 28517434
TI  - SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte
      Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.
AB  - PURPOSE: Accurate determination of proton dosimetric effect for tissue
      heterogeneity is critical in proton therapy. Proton beams have finite range and
      consequently tissue heterogeneity plays a more critical role in proton therapy.
      The purpose of this study is to investigate the tissue heterogeneity effect in
      proton dosimetry based on anatomical-based Monte Carlo simulation using animal
      tissues. METHODS: Animal tissues including a pig head and beef bulk were used in
      this study. Both pig head and beef were scanned using a GE CT scanner with 1.25
      mm slice thickness. A treatment plan was created, using the CMS XiO treatment
      planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP).
      Radiochromic films were placed at the distal falloff region. Image guidance was
      used to align the phantom before proton beams were delivered according to the
      treatment plan. The same two CT sets were converted to Monte Carlo simulation
      model. The Monte Carlo simulated dose calculations with/without tissue omposition
      were compared to TPS calculations and measurements. RESULTS: Based on the
      preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation
      dose without tissue composition agreed generally well with TPS calculation. In
      the distal falloff region, the dose difference was large, and about 2 mm isodose
      line shift was observed with the consideration of tissue composition. The
      detailed comparison of dose distributions between Monte Carlo simulation, TPS
      calculations and measurements is underway. CONCLUSIONS: Accurate proton dose
      calculations are challenging in proton treatment planning for heterogeneous
      tissues. Tissue heterogeneity and tissue composition may lead to isodose line
      shifts up to a few millimeters in the distal falloff region. By simulating
      detailed particle transport and energy deposition, Monte Carlo simulations
      provide a verification method in proton dose calculation where inhomogeneous
      tissues are present.

PMID- 28517435
TI  - SU-E-T-452: Impact of Abdominal Compression on the Tumor Motion in the Treatment
      of NSCLC Using Stereotactic Body Radiosurgery.
AB  - PURPOSE: Involuntary motion of the tumor during the treatment of NSCLC using
      stereotactic body radiosurgery presents its own unique challenges. In this study,
      we quantify the impact of abdominal compression technique to minimize tumor
      motion as a function of location of tumor in a patient. METHODS: 25 patients (5
      in each lung lobe viz. RUL, RML, RLL, LUL and LLL) were retrospectively analyzed.
      A 4DCT study encompassing the tumor was used on a 16 slice GE CT scanner along
      with Varian RPM gating system. The images were retrospectively binned in 10
      phases. The motion of tumor was analyzed phase by phase in transverse, sagittal &
      coronal projections of the 3D image. This gave us 2 values for anterior
      posterior, superior-inferior and lateral-medial motions each and was averaged
      out. RESULTS: Analysis of data reveals that the motion (mean +/- 1SD) in the
      superior-inferior direction was 1.8 +/- 0.9, 4.2+/-2.8, 7.4+/-2.3, 1.5+/-0.8,
      3.1+/-2.8 mm for tumors located in RUL, RML, RLL, LUL and LLL, respectively.
      Along the anterior-posterior direction the respective values were 2.5 +/- 1.9,
      2.4 +/- 1.1, 2.7 +/- 1.3, 1.4 +/- 0.2 and 1.8 +/- 1 mm. Similarly, along the
      lateral direction, the respective values were 2.1 +/- 1.1, 1.9 +/- 1.1, 1.6 +/-
      1.3, 1.1 +/- 0.3 and 1.8 +/- 0.7 mm. When the data was analyzed removing the
      location of the tumor in the thorax, the median displacement along the superior
      inferior, anterior-posterior, lateral direction was 2.3, 1.6 and 1.5 mm,
      respectively while the respective maximum value were 9.2, 5 & 3.8 mm.
      CONCLUSIONS: The use of abdominal compression provides a simple inexpensive yet
      easily tolerable device to control the motion of the tumor in the management of
      NSCLC for SBRT treatments. This will allows the treatment of the tumor without
      resorting to complex and time consuming gated treatments.

PMID- 28517436
TI  - SU-E-T-492: The Dosimetric and Clinical Impact of the Metallic Dental Implants on
      Radiation Dose Distributions in IMRT Head and Neck Cancer Patients.
AB  - PURPOSE: In H&N cancer patients, the development of oral mucositis is related
      closely to the radiation dose to the oral cavity. It is generally presumed that
      the existence of metallic dental implants makes it worse due to the scattering
      effect of the metal. This study investigates the effects of the dental implants
      on radiation doses to PTV, tongue mucosa, and other structures for IMRT H&N
      cancer patients by Monte Carlo (MC) dose calculations. METHODS: Two H&N cancer
      patients who have dental implant and are treated by IMRT technique are selected
      for the purpose. The BEAMnrc/DOSXYZnrc MC codes are employed for the CT-image
      based dose calculations. The radiation sources are the validated Varian phase
      space files for 6MV linac beams. The CT image artifacts caused by the dental
      fillings are replaced by tissue material. Two sets of MC calculations for each
      patient are performed at a calculation statistics of 1%: one treats all dental
      implants as bones, the other substitutes the implants by metal of either titanium
      or gold with correct density. Doses in PTV and various tissue structures are
      compared for the two scenarios. RESULTS: With titanium implant, there is no
      significant difference in doses to PTV and tongue mucosa from that when treating
      implant as bone. With gold implant, the mean dose to PTV is slightly lowered by
      1%; the mean dose to tongue mucosa is reduced by less than 0.5%, although the
      maximum dose is increased by 5%. CONCLUSIONS: The scattering dose from titanium
      implants is not of concern for H&N patients irradiated by 6MV IMRT beams. For
      gold implants, the scattering dose to tongue mucosa is not as severe as presumed;
      and the dose to PTV could be slightly compromised due to the attenuation effect
      of the metal. This work was supported in part by Varian Medical Systems.

PMID- 28517437
TI  - SU-E-T-463: Biological-Based Optimization and VMAT is Unnecessary for
      Stereotactic Body Radiation Therapy.
AB  - PURPOSE: This study shows that there is no clear dosimetric benefit of biological
      based optimization for either fixed-beam IMRT or VMAT. Other than shorter
      delivery times, even VMAT does not offer additional advantage to fixed-beam IMRT.
      METHODS: A small number of patients for lung, pancreas, spine and brain CA were
      planned with fixed-beam IMRT, optimized with (gEUD) and without (DV) biological
      objectives and, also planned for VMAT with and without gEUD, for comparison. For
      the lung and brain cases, a non-coplanar 7-11 beam arrangement was used for fixed
      beam IMRT and a coplanar 'hybrid' arc simulated VMAT with beams set every 5
      degrees  spacing. For the other treatment sites, all beams were coplanar. For
      each case, the fixed-beam IMRT and VMAT plans were optimized with the same
      objectives. It is important to note that, only 2 segments/beam were allowed for
      each plan, in order to create small fluence modulation, appropriate for small
      target volumes during SBRT. RESULTS: For all plans we noticed that there were
      minor or no dosimetric differences between fixed- beam IMRT and VMAT, whether DV
      or gEUD objectives were used or whether fixed-beam IMRT or VMAT is used. Keeping
      the level of beam modulation as-low-as possible, for small SBRT targets, one can
      show that VMAT with or without gEUD optimization does not offer any dosimetric
      advantage against fixed-beam IMRT with multiple non-coplanar beams. This is
      against the expectation that gEUD-optimization can Result superior plans than DV
      optimization. The difference is that, for small target volumes like those
      encountered in SBRT, the complexity of the fluence is not as high as in large
      field intensity modulated cases. CONCLUSIONS: The fact that VMAT with or without
      gEUD can produce as good plans as fixed-IMRT does not make VMAT a preferred
      treatment modality, other than the fact that requires reduced treatment time.

PMID- 28517438
TI  - SU-E-T-474: Monte Carlo Phase Space Production to Model Magnetically Scanned
      Proton Beams for IMPT.
AB  - PURPOSE: Accurate dose predictions in proton beam therapy using magnetically
      scanned beams are highly dependent on the accurate modeling of the lateral dose
      profiles. This study was performed to provide proton phase spaces for Monte Carlo
      simulations, used to accurately simulate doses at distances up to 12 cm from the
      central axis of the beam. METHODS: Measured lateral dose profiles at various
      depths in water were compared to Monte Carlo simulations of doses for 90 discreet
      initial proton energies. Phase spaces were produced using a one dimensional
      energy distribution, and a combination of several two dimensional spatial and
      directional distributions. Simulations were performed iteratively using
      variations in the initial phase space distributions to achieve acceptable
      agreement between measured and simulated lateral dose profiles, i.e. differences
      in FWHM < 0.5 mm and dose differences less that 0.1% at distances up to 12.5 cm.
      RESULTS: 90 phase spaces of proton sources for different initial beam energies
      were created for use in Monte Carlo simulations of scanned proton beam therapy
      patient plans. At a depth of 2 cm in water, the simulated and measured FWHM of
      the lateral dose profiles differed in in-plane direction by an average of 0.05
      mm, in cross-plane direction by 0.13 mm. All simulated profiles were within 0.1%
      of the measured doses at distances between 2cm and 12.5 cm from the central beam
      axis. CONCLUSIONS: A library of 90 phase space files has been created to
      accurately simulate magnetically scanned proton beams for IMPT, providing
      accurate dose distributions up to 12 cm distance from the central beam axis. This
      project is supported in part by P01CA021239 from the National Cancer Institute.
      The content is solely the responsibility of the authors and does not necessarily
      represent the official views of the National Cancer Institute or the National
      Institutes of Health.

PMID- 28517439
TI  - SU-E-T-445: A Dosimetric Comparison of Gamma Knife Plans with Measurement Based
      and Image Based Skull Definitions.
AB  - PURPOSE: To compare gamma knife treatment plans that use skull scaling instrument
      measurements for skull definition vs. CT based skull definition. METHODS: Eight
      previously treated patients who had head CT scans were randomly selected. Their
      CT images were imported into Leksell GammaPlan. For each patient, three dose
      plans were developed: 1. the reference plan. It was planned based on the standard
      clinical treatment planning guidelines. Measurements were used for skull
      definition and TMR10 for dose calculation algorithm. 2. CT TMR10 plan, a
      recalculation of the reference plan with CT images used for skull definition 3.
      CT Convolution plan, a recalculation of the TMR10 plan using convolution
      algorithm. The treatment times for CT TMR10 plan and CT convolution plan were set
      to be the same as the reference plan by adjusting the prescription dose level.
      Prescription dose and shots were left unchanged. Plan comparisons were carried
      out using minimum dose, target coverage, gradient index and selectivity. RESULTS:
      On average, the minimum dose for CT TMR10 and CT Convolution plans are 1.8% and
      6.5% lower than that of the reference plan. The target coverage, gradient index
      are comparable for these three plans. The selectivity indices for CT TMR10 and CT
      Convolution plans were found to be 3.1% and 9.8% higher than that of reference
      plan. CONCLUSIONS: This work indicates the measurement based skull definition
      could Result in inaccurate calculation in minimum dose to the target. The target
      coverage and gradient index are however uncompromised. The selectivity index was
      actually underestimated.

PMID- 28517440
TI  - SU-E-T-485: Validation of Acuros XB Dose Calculations in SBRT Lung Planning with
      Monte Carlo Methods.
AB  - PURPOSE: The Acuros XB (AXB) Advanced Dose algorithm (Varian Medical Systems)
      represents a dramatic shift in clinical photon dose calculation methodology from
      pencil-beam superposition/convolution methods. Early studies evaluating the
      accuracy of the algorithm in lung have found good agreement with both measurement
      and Monte Carlo based dose calculations. In this study, a dosimetric validation
      of Acuros is performed for clinical SBRT lung planning cases using Monte Carlo
      (MC) calculations as a benchmark. METHODS: MC simulations using BEAMnrc/DOSXYZnrc
      were carried out for 8 AXB calculated 6/10 MV arc plans delivered on a TrueBeamTM
      STx linac in high-dose-rate flattening filter free mode. Clinical planning
      constraints were applied in each case with plans normalized to achieve 95% PTV
      coverage. Metrics used in the evaluation include: maximum and minimum GTV/PTV
      dose, PTV isodose coverage, conformity and dose profile comparisons. To
      understand the impact of moving toward to AXB calculations in SBRT lung planning,
      calculations using the Analytical Anisotropic Algorithm (AAA) are presented for
      each plan. RESULTS: For both 6 and 10MV energies, consistent mean GTV dose and
      PTV isodose coverage was observed for AXB and MC calculations. GTV mean dose was
      observed to deviate by <2% for all cases. Isodose coverage for MC simulations
      ranged from 92%-98%. AAA was also in agreement with MC simulations within the GTV
      to within 2%. AXB and MC maximum and minimum PTV dose differences were larger (up
      to 9%) but not of clinical concern. In several cases, AXB exhibited a significant
      improvement in dose calculation accuracy in the lung region surrounding the GTV
      over AAA, particularly with lung densities < 0.1 g/cc. CONCLUSION: AcurosXB
      provides increased accuracy in modelling dose deposition for SBRT lung over AAA
      and is found to be in good agreement with MC calculations.

PMID- 28517441
TI  - SU-E-T-456: Potential Optimization of Stereotactic Body Radation Therapy (SBRT)
      from a Simple Field Timing Rearrangement.
AB  - PURPOSE: Stereotactic Body Radiation Therapy (SBRT) is a radiotherapy technique
      which uses high dose fractions with multiple coplanar and non- coplanar beams.
      Treatments are typically protracted with more fields than conventional radiation
      treatment schemes. The timing of field delivery may have an impact on the
      radiobiological results for SBRT. METHODS: In a cohort of eight SBRT patient
      treatments, the protraction factor (G-value), LPL, and LQL models were used to
      optimize field arrangements. An actual field timing delivered in the clinic (C)
      was included for comparison. The LPL model was used to quantify the difference in
      survival fractions (SF). Published data from three cell lines for non-small cell
      lung cancers: H460, H660, and H157 was used to acquire the model parameters. The
      results were displayed as (C:O)N or (V:O)N, where C, V, and O were the SF for the
      clinical (C), least favorable (V), and optimal (O) field timings respectively. N
      represents the number of fractions for the SBRT protocol. RESULTS: Results from
      all three models indicate that the optimal field order occurs when the fields are
      arranged in a triangle like pattern, where the highest dose fields are positioned
      centrally. Minimization of cell kill was achieved with a V-shaped orientation,
      although these results were not as conclusive. Results of the SF ratios
      demonstrated that regardless the cell type and model the triangle shape had lower
      cell survival fractions compared to both the C and the V arrangement. For
      example, the H460, with repair half-time = 1.50 h, an average ratio of (C:O)3 =
      5.8, suggesting the triangle pattern is approximately 6 times more effective than
      the clinical plan, after 3 fractions. CONCLUSIONS: Rearranging field timing for a
      SBRT treatment so that maximal dose is deposited in the central fields of
      treatment may optimize cell kill and potentially affect overall treatment
      outcome.

PMID- 28517442
TI  - SU-E-T-496: Monte Carlo Simulation of a 6MV Varian Truebeam Without Flattening
      Filter Linac.
AB  - PURPOSE: To simulate a 6 MV Varian Truebeam linac operating without flattening
      filter using an existing Phase space file(PhS) with the monte carlo packeage
      EGSnrc. METHODS: An existing PhS file built after simulating the patient
      independent part at the first step in traditional monte carlo simulation was
      employed. With this PhS being a source, the patient-dependent part was simulated
      and the dose distributions were calculated using EGSnrc. The 6 MV dose
      calculation were performed for field size of 10*10cm2 , 20*20cm2 , 30*30cm2 and
      40*40cm2 in a 54*54*30 cm3 water phantom. The voxel size for the water phantom
      was 0.6*0.6*0.6cm3 . For the 10*10cm2 field, surface buildup calculations were
      performed using 0.6*0.6*0.3cm3 voxels within 1.8cm of the surface. Dose profiles
      and percent depth dose(PDD) curves were calculated following 1 billion histories
      for dose profiles and 500 million histories for PDD curves. Simulation results
      were compared with measured data for validation. RESULTS: Good agreement between
      simulations and measurements in water was observed. For the PDD curves, 95% of
      the calculated data points agree within 2% with the experimental measurements for
      depths between 1.8cm and 30 cm. In the buildup region, the agreement is within
      2%, except several points with the deviation of 5% for the 10*10 cm2 open field.
      For the lateral dose profiles, the agreement is less than 3% at the depth of
      1.3cm, 5cm, 10cm, 20cm and 30cm inside the 80% field size. CONCLUSIONS: It
      demonstrated that the existing phase space file is accurate and the simulation is
      reliable to be used for clinical patient dose calculations in future
      investigations. Project supported by the National Natural Science Foundation of
      China (30970866).

PMID- 28517443
TI  - SU-E-T-467: Monte Carlo Dosimetric Study of the New Flexisource Co-60 High Dose
      Rate Source.
AB  - PURPOSE: Recently, a new HDR 60Co brachytherapy source, Flexisource Co-60, has
      been developed (Nucletron B.V.). This study aims to obtain quality dosimetric
      data for this source for its use in clinical practice as required by AAPM and
      ESTRO. METHODS: Penelope2008 and GEANT4 Monte Carlo codes were used to
      dosimetrically characterize this source. Water composition and mass density was
      that recommended by AAPM. Due to the high energy of the 60Co, dose for small
      distances cannot be approximated by collisional kerma. Therefore, we have
      considered absorbed dose to water for r<0.75 cm and collisional kerma from
      0.75<r<20 cm. To provide adequate spatial resolution, cells were 0.01 cm in
      thickness for r<2 cm from the source and a factor of 10 thicker for 2<r<20 cm
      respectively. Angular sampling was taken every 2 degrees . Additional simulations
      were performed to obtain SK as recommended by AAPM. Mass-energy absorption
      coefficients in water and air were consistently derived and used to calculate
      collisional kerma. Along-away tables and TG-43 formalism parameters and functions
      were derived. Dosimetric data were also provided following the primary and
      scatter dose separation for the collapsed cone technique. RESULTS: TG-43
      dosimetry parameters with L = 0.35 cm were obtained. Results performed with both
      radiation transport codes showed agreement typically within 0.2% for r > 0.8 cm
      and up to 2% closer to the source. Using Penelope2008 and GEANT4, an average of
      I> = 1.085+/-0.003 cGy/(h U) (with k = 1, Type A uncertainties) was obtained.
      Dose rate constant, radial dose function and anisotropy functions for the
      Flexisource Co-60 are compared with published data for other Co-60 sources.
      CONCLUSIONS: Dosimetric data are provided for the new Flexisource Co-60 source
      not studied previously in the literature. Using the data provided by this study
      in the treatment planning systems, it can be used in clinical practice. This
      project has been funded by Nucletron BV.

PMID- 28517444
TI  - SU-E-T-478: Geometrical Splitting Technique to Improve the Computational
      Efficiency in Monte Carlo Calculations for Proton Therapy.
AB  - PURPOSE: To implement a geometry based particle splitting technique in order to
      reduce the computation time when generating treatment head phase space files for
      proton therapy dose calculations using Monte Carlo (MC) calculations and to
      validate the doses generated from these phase spaces with respect to reference
      simulations. METHODS: The treatment nozzles at the Francis H Burr Proton Therapy
      Center (FHBPTC) were modeled with a new MC tool ('TOPAS' based on Geant4). For
      variance reduction purposes, two particle-splitting planes were implemented, one
      downstream of the second ionization chamber the other upstream of the aperture of
      the nozzle and phase spaces in IAEA format were recovered. The symmetry of the
      proton beam was considered to split the particles by a factor of 4 per plane.
      Split particles were randomly positioned at different locations rotated around
      the beam axis. The computational efficiency was calculated and dose profiles
      compared for a voxelized water phantom for different treatment fields for both
      the reference and optimized simulations. Depth-dose curves and beam profiles were
      analyzed. Dose calculation in patients was simulated to compare the performance.
      RESULTS: Normalized computational efficiency between 10 and 14.5 were reached.
      Percentage difference between dose profiles in water for simulations done with
      and without particle splitting is within the statistical precision of 2%, 1
      standard deviation. Dose distributions for the realistic patient treatment show
      differences up to 4% in the regions of interest, within 2 standard deviations.
      CONCLUSIONS: By considering the cylindrically symmetric region of the nozzle and
      the splitting planes separated at strategic distance, considerable time reduction
      can be achieved without compromising the precision. This approach will reduce the
      time for phase space simulations for clinical MC dose calculation at FHBPTC by
      more than a factor of 10.

PMID- 28517445
TI  - SU-E-T-449: Dosimetric Comparison of Beam Arrangements for Stereotactic Body
      Radiotherapy of Lung Lesion.
AB  - PURPOSE: Dosimetric comparison of beam arrangements of coplanar, non- coplanar
      and conformal arc for Stereotactic body radiotherapy of lung lesion. METHODS:
      Four spherical targets with diameters of 2, 4, 6 and 7cm are contoured in the
      geometric center of right lung of a selected SBRT CT scan. For each target,
      treatment plans of optimized 7, 9 and 11 coplanar, non- coplanar and conformal
      arc beam arrangements are generated in Pinnacle (Pinnacle Version 9.0, Philips
      Radiation Oncology Systems, WI). Prescription isodoses are chosen to cover at
      least 95% of target volumes. The volumes enclosed by the prescription and 50% of
      prescription isodose surfaces are computed. Conformality index (CI) and effective
      dose fall off gradient are computed for dosimetric comparison. RESULTS: All plans
      with optimized coplanar and conformal arc beam arrangements have similar CIs
      while optimized non-coplanar beam arrangements have the smallest CIs. For each
      target size, optimized 7 and 9 coplanar beam arrangements have the largest half
      prescription isodose volumes while optimized 11 coplanar beam arrangements have
      slightly less half prescription isodose volumes than conformal arc plans. All 3
      optimized non-coplanar beam arrangements Result in faster dose gradient than
      conformal arcs except for the smallest target cases, for a 2cm diameter target, 9
      or 11 non-coplanar beams are needed to achieve better dose gradient than their
      rival conformal arc plan. CONCLUSIONS: Treatment plans using optimized 9 and 11
      non-coplanar beam arrangements are superior to conformal arc plans for SBRT of
      lung lesions based on dosimetric comparison. To achieve a superior plan for small
      lesions, 11 or more optimized coplanar beams may be required.

PMID- 28517446
TI  - SU-E-T-489: Quantum versus Classical Trajectory Monte Carlo Simulations of Low
      Energy Electron Transport.
AB  - PURPOSE: Widely-used classical trajectory Monte Carlo simulations of low energy
      electron transport neglect the quantum nature of electrons; however, at sub-1 keV
      energies quantum effects have the potential to become significant. This work
      compares quantum and classical simulations within a simplified model of electron
      transport in water. METHODS: Electron transport is modeled in water droplets
      using quantum mechanical (QM) and classical trajectory Monte Carlo (MC) methods.
      Water droplets are modeled as collections of point scatterers representing water
      molecules from which electrons may be isotropically scattered. The role of
      inelastic scattering is investigated by introducing absorption. QM calculations
      involve numerically solving a system of coupled equations for the electron
      wavefield incident on each scatterer. A minimum distance between scatterers is
      introduced to approximate structured water. The average QM water droplet
      incoherent cross section is compared with the MC cross section; a relative error
      (RE) on the MC results is computed. RESULTS: RE varies with electron energy,
      average and minimum distances between scatterers, and scattering amplitude. The
      mean free path is generally the relevant length scale for estimating RE. The
      introduction of a minimum distance between scatterers increases RE substantially
      (factors of 5 to 10), suggesting that the structure of water must be modeled for
      accurate simulations. Inelastic scattering does not improve agreement between QM
      and MC simulations: for the same magnitude of elastic scattering, the
      introduction of inelastic scattering increases RE. Droplet cross sections are
      sensitive to droplet size and shape; considerable variations in RE are observed
      with changing droplet size and shape. CONCLUSIONS: At sub-1 keV energies, quantum
      effects may become non-negligible for electron transport in condensed media.
      Electron transport is strongly affected by the structure of the medium. Inelastic
      scatter does not improve agreement between QM and MC simulations of low energy
      electron transport in condensed media.

PMID- 28517447
TI  - SU-E-T-460: Isoeffective Dose Display (EQD2) for Composite Plan of Radiosurgery
      and Conventional 3D Radiotherapy.
AB  - PURPOSE: Direct addition of doses between plans with different fractionation
      fails to provide accurate dose-response information to anticipate clinical
      outcome. To combine different fractionation patterns, first-order biological
      model correction for dose-rate must be included. Moreover, 3-D isoeffect patterns
      of the combined doses must be displayed so that overlap area to elegant volumes
      can be avoided. The linear quadratic (LQ) model and biologically effective dose
      (BED) method were used to produce a combined plan in equivalent 2 Gy fractions
      (EQD2) for radiosurgery and conventional 3D radiotherapy. METHODS: For patients
      with multiple courses of radiotherapy, dose distributions of the prior and boost
      treatment plans were converted to BED. The fraction size specified by the
      prescription was applied globally for each BED calculation, alpha/beta ratio of
      10 and 2.5 was used for early and late effect, respectively. Image registration
      with CT or MR was performed for initial and boost plans. The registration
      information was applied to dose distributions to obtain the composite EQD2.
      RESULTS: As a demonstration of this method, two patients were selected who had
      combined treatments from substantially different modalities. A patient with liver
      cancer initially received radiotherapy of 30 Gy/10 Fx and re-irradiation with
      CyberKnife radiosurgery (15 Gy/1 Fx). The combined plan showed that the PTV
      received EQD2 of 63.8 Gy. Another patient had brain metastasis treated with
      GammaKnife of 18 Gy (50% isodose) followed by conventional 3D whole brain
      radiation of 30 Gy/10 Fx. The minimal combined tumor EQD2 was 74.5 Gy. Early and
      late calculated responses showed that all critical organ doses were within
      tolerance. CONCLUSIONS: For patients receiving radiation with different
      fractionation schemes, combined isoeffective dose distributions were calculated
      and displayed. In both cases, crucial information regarding 3-D dose
      distributions assisted the physicians in determining whether tolerance limits of
      overlap areas of retreated critical structures were preserved.

PMID- 28517448
TI  - SU-E-T-451: Optimization of Normalized Prescription Isodose Selection for
      Stereotactic Radiation Therapy: Conventional Vs. Robotic Linac.
AB  - PURPOSE: To determine the optimal prescription isodose line that minimizes normal
      tissue irradiation for stereotactic radiation therapy comparing conventional
      linear accelerator and robotic delivery. METHODS: A computer based digital torso
      phantom which has the capability to simulate respiratory and cardiac motion were
      used in this study. Spherical targets were constructed in lung and liver, with
      diameter of 20mm, 30mm, and 40mm. Two concentric 5mm shells, from the target
      surface extending 5mm radially and from 5mm to 10mm, were identified/contoured.
      Non-coplanar, non- opposing 3D conformal beams were designed for linac planning.
      Variable prescription isodose lines were achieved by varying the block margin. 4D
      dose calculation was used for moving target and surrounding tissue. After linac
      planning, the CT images and contours were transferred for Cyberknife(r) planning.
      Variable prescription isodose lines were achieved by inverse planning technique.
      Doses of 60Gy in 3 fractions were prescribed to cover exactly 95% of target tumor
      with each technology. gEUD (generalized effective uniform dose) with different
      formulations for parallel and serial tissues was used for comparison between
      different plans. RESULTS: For linac plans, the optimal prescription isodose line
      yielding maximum normal tissue sparing occurs between 50% and 70% for the lung
      tumor and 60% and 90% for liver tumor. The gEUD difference between plans with
      optimum and arbitrarily chosen prescription isodose line may be up to 20% of
      prescription dose. For Cyberknife plans, the optimal prescription isodose line is
      approximately 50% for tissues displaying either parallel or serial behavior.
      These results are similar for different tumor sizes. CONCLUSIONS: Both
      conventional linac and Cyberknife(r) delivery can provide conformal tumor
      coverage with normal tissue sparing. By carefully choosing the optimal
      prescription isodose line, the gEUD of the surrounding normal tissue can be
      reduced by up to 20% of prescription dose.

PMID- 28517449
TI  - SU-E-T-491: A FLUKA Monte Carlo Computational Model of a Scanning Proton Beam
      Therapy Nozzle at IU Proton Therapy Center.
AB  - PURPOSE: Charged particle therapy, especially proton therapy is a growing
      treatment modality worldwide. Monte Carlo (MC) simulation of the interactions of
      proton beam with equipment, devices and patient is a highly efficient tool that
      can substitute measurements for complex and unrealistic experiments. The purpose
      of this study is to design a MC model of a treatment nozzle to characterize the
      proton scanning beam and commissioning the model for the Indiana University
      Health Proton Therapy Center (IUHPTC. METHODS: The general purpose Monte Carlo
      code FLUKA was used for simulation of the proton beam passage through the
      elements of the treatment nozzle design. The geometry of the nozzle was extracted
      from the design blueprints. The initial parameters for beam simulation were
      determined from calculations of beam optics design to derive a semi-empirical
      model to describe the initial parameters of the beam entering the nozzle. The
      lateral fluence and energy distribution of the beam entering the nozzle is
      defined as a function of the requested range. The uniform scanning model at the
      IUHPTC is implemented. The results of simulation with the beam and nozzle model
      are compared and verified with measurements. RESULTS: The lateral particle
      distribution and energy spectra of the proton beam entering the nozzle were
      compared with measurements in the interval of energies from 70 MeV to 204.8 MeV.
      The accuracy of the description of the proton beam by MC simulation is better
      than 2% compared with measurements, providing confidence for complex simulation
      in phantom and patient dosimetry with the MC simulated nozzle and the uniform
      scanning proton beam. CONCLUSIONS: The treatment nozzle and beam model was
      accurately implemented in the FLUKA Monte Carlo code and suitable for the
      research purpose to simulate the scanning beam at IUHPTC.

PMID- 28517450
TI  - SU-E-T-462: Calculation of Prescribed Dose for Permanent Implant with Cs-131
      Using LQ Equation including Resensitization.
AB  - PURPOSE: To develop a new biological equivalent dose (BED) formulism that
      includes repair, repopulation and resensitization (redistribution and
      reoxygenation), and can be used to calculate prescribed dose for permanent
      implant with Cs-131. METHODS: Because of lack of sufficient clinical data, the
      prescribed dose with new isotopes is usually calculated based on BED compared
      with other isotopes that have already been used in clinical practice. The current
      widely used formulism of BED calculation for permanent implant which was given by
      Dale includes cell repair and repopulation but not resensitization.
      Resensitization can be included in the extended LQ equation (LQR) proposed by
      Brenner. Applying Dales formulism to Brenners LQR, we obtained a new BED
      calculation formula that accounts for resensitization. We used this new formulism
      to calculate the BED that corresponds to the prescribed dose for cervix (with Au
      198) and prostate (with I-125) permanent implant. Then, we obtained the
      prescribed dose with Cs-131 which has the same BED as Au-198 or I-125. RESULTS:
      The new formulism was used for prostate and cervix cancer permanent implant. The
      prescribed dose with Cs-131 for cervix was 40 Gy (42 Gy without resensitization)
      and 66 Gy (69 Gy without resensitization) which were equivalent to 35 Gy and 60
      Gy with Au-198, respectively. For prostate implant, the prescribed dose with Cs
      131 that corresponded to 144 Gy with I-125 was 135 Gy (124 Gy without
      resensitization). CONCLUSION: Resensitization led to significant dose correction
      for permanent implant. The calculation of BED and dose was dependent on dose
      itself and thus should be patient-specific. Since this calculation relied on many
      biological parameters, and may not be accurate if the parameters are not
      accurate. Also, the dose prescription should be adjusted based on clinical
      outcomes.

PMID- 28517451
TI  - SU-E-T-473: Performance Assessment of the TOPAS Tool for Particle Simulation for
      Proton Therapy Applications.
AB  - PURPOSE: The TOPAS Tool for Particle Simulation was developed to make Geant4
      Monte Carlo simulation more readily available for research and clinical
      physicists. Before releasing this new tool to the proton therapy community,
      several test have been performed to ensure accurate simulations in a variety of
      proton therapy setups. METHODS: TOPAS can model a passive scattering or scanning
      beam treatment head, model a patient geometry based on CT images, score dose,
      fluence, etc., save and replay a phase space, provides advanced graphics, and is
      fully four-dimensional (4D) to handle variations in beam delivery and patient
      geometry during treatment. An innovative control system meets requirements for
      ease of use, reliability and repeatability without sacrificing flexibility. To
      test the TOPAS code, we modeled proton therapy treatment examples including the
      UCSF eye treatment beamline (UCSFETB), the MGH STAR radiosurgery beamline and the
      MGH gantry treatment head in passive scattering and scanning modes. The
      simulations included time-dependent geometry and time- dependent beam current
      delivery. RESULTS: At the UCSFETB, time- dependent depth dose distributions were
      accurately simulated with time- varying energy modulation from a rotating
      propeller. At the MGH STAR beamline, distal and proximal ranges agreed within
      measurement uncertainty and the shape of the simulated SOBP followed measured
      data. For the MGH gantry treatment head in passive scattering mode, SOBPs were
      simulated for the full set of range modulator wheel and second scatterer
      combinations. TOPAS simulation was within clinical required accuracy. For the MGH
      nozzle in scanning mode, a variety of scan patterns were simulated with fluence
      maps generated for cases including beam current modulation, energy modulation and
      target tracking. CONCLUSIONS: Our results demonstrate the functionality of TOPAS.
      They show agreement with measured data and demonstrate the capabilities of TOPAS
      in simulating beam delivery in 3D and 4D. This work was supported by IH/NCI under
      R01 CA 140735-01.

PMID- 28517452
TI  - SU-E-T-444: 4D-CT and Active Breathing Coordinator Play Similar Role in Sparing
      Normal Liver Tissue in the Radiotherapy of Hepatocellular Carcinoma.
AB  - PURPOSE: To investigate the difference in sparing normal liver tissue between 4D
      CT and active breathing coordinator (ABC) in the radiotherapy of Hepatocellular
      carcinoma(HCC) applying RapidArc. METHODS: Ten patients with HCC underwent 3D-CT
      at end inspiration hold(EIH) associated with active breathing
      coordinator(ABC),and 4D-CT scan. The 4D-CT images were sorted in to 10 serious CT
      images according respiratory phase. Gross tumor volumes(GTVs) were manually
      contoured on different CT images. The individual internal gross target
      volume(IGTV) was obtained from 10 GTVs of 4D-CT images. Plan target volumes
      (PTVs) were obtained based on IGTV and GTVEIH. PTV1 was obtained from IGTV plus 5
      mm margins isotropically, and PTV2 was obtained from GTVEIH using 8 mm margins
      isotropically. RapidArc plans were designed on PTV1 and PTV2, for PTV1 RapidArc
      plans with one single whole arc were applied and for PTV2 three 135 degrees arcs,
      and name RapidArc1 and RapidArc2. Dosimetric differences were compared. RESULTS:
      There were no significant difference in conformity index (0.93+/-0.05 Vs 0.93+/
      0.03), homogeneity index(1.08+/-0.01 Vs 1.08+/-0.01), the Dl%(54.44+/-0.36 Gy
      Vs54.68+/-0.47 Gy) and D99%(49.18+/-0.48Gy Vs 49.00+/-0.34 Gy) between RapidArc1
      and RapidArc2(P>0.05). There were no significant differences in the mean
      dose(8.23+/-1.5Gy Vs 7.63+/-3.00Gy),V5(46.64+/-19.31Vs43.29+/-19.94), V10(28.73+/
      11.54 Vs 28.23+/-12.37), V15(17.87+/-6.61 Vs 18.20+/-7.55), V20(11.62+/-4.39 Vs
      11.83+/-4.58), V25(7.71+/-2.91Vs 7.58+/-2.79),V30(5.14+/-2.01Vs5.05+/-1.79),
      35(3.41+/-1.35Vs 3.35+/-1.21) and V40(2.12+/-0.86Vs2.06+/-0.75) between RapidArc1
      and RapidArc2 (P>0.05). CONCLUSIONS: The RapidArc plans with three 135 degrees
      arcs associated could achieve similar dose delivery as the plans with single
      whole arc, and 4D-CT and ABC could play similar role in sparing normal liver
      tissue assuring the accuracy of target volume in radiotherapy of HCC.

PMID- 28517453
TI  - SU-E-T-484: Potential Clinical Impact of Dosimetric Uncertainties in Proton
      Therapy.
AB  - PURPOSE: The analytical algorithms which are used widely for proton treatment
      planning in the current clinical practice may have significant dosimetric
      uncertainties in highly heterogeneous regions. The aim of this study is the
      assessment of the potential clinical impact of these uncertainties. METHODS: A
      cohort of 8 patients with local (in field) recurrences, originally treated for
      lung cancer at our institution, was selected for this study. CT scans and
      treatment plans were used to assemble the input files for the Monte Carlo (MC)
      code MCNPX. The total energy deposition inside the patient volume was computed
      with statistical uncertainty of less than 2% and converted to dose-in-water. The
      results were compared to the dose computed by the clinical treatment planning
      system (TPS). The area of the recurrence was contoured on the follow-up PET/CT
      study for each of the patients and registered to the planning CT. RESULTS: While
      there is acceptable agreement between the TPS and the Monte Carlo dose in
      homogeneous regions, there are noticeable differences caused by heterogeneities.
      The regions of largest differences are the points around and beyond the distal
      edge and points around the lateral penumbra and in several patients the target
      has received lower then the prescribed dose. The area of the recurrence corelates
      well with the MC predicted underdosed area of the target. CONCLUSIONS: The
      uncertanties in analytical dose algorithms used in clinical TPSs may result in
      suboptimal target coverage increasing the possibility of tumor recurrence.
      Accurate Monte Carlo simulations can be used to predict and avoid the situations
      in which the analytical algorithms have high uncertanties providing for more
      robust treatment planning.

PMID- 28517454
TI  - SU-E-T-455: Novel Planning Techniques for Lung SBRT.
AB  - PURPOSE: Two new planning techniques in lung SBRT are presented. The first
      technique involves a differential dosing strategy for patients with compromised
      pulmonary function. The second technique compares supine vs prone setup for
      extreme posterior lesions. CyberKnifeTM(CK) prone setup is complicated due to
      patient discomfort from longer treatment times and the inability to track without
      fiducials. METHODS: CK(G.3) MultiplanTM(V3.5). SynchronyTM, XSightTM Lung
      Tracking Systems. Our lung SBRT patients are tracked using fiducials with
      Synchrony or without fiducials with XSight using a 60 Gy in three fractions
      scheme. If the ray-tracing optimized plan results in V15Gy greater than 10% we
      employ the differential dosing technique. A new PTV is created to encompass the
      54 Gy isodose surface. A more conformal plan with a dose constraint of 60Gy to
      CTV and 54Gy to PTV is created appreciably lowering the V15Gy. Alternatively a
      54Gy PTV can be created from measured respiration excursions. For the
      prone/supine comparison, plans were generated for both positions then evaluated.
      RESULTS: Patients planned with the differential dose technique have a good tumor
      response as evidenced by a follow-up PET. Although prone setup is preferred for
      extremely posterior tumors, a dosimetrically comparable supine plan can be
      created to replicate the prone plan. The supine low dose spillage was only
      slightly greater than in the prone case. CONCLUSIONS: We conclude that the
      54Gy/60Gy dosed patients have almost the same tumor response as the standard 60
      Gy treatment. A dosimetrically similar supine plan obviates the need for a prone
      delivery.

PMID- 28517455
TI  - SU-E-T-495: Monte Carlo Dose Verification of Passive Scattering Proton Therapy
      for Prostate Cancer.
AB  - PURPOSE: To verify the clinical pencil beam dose calculation algorithm for
      passive scattering proton therapy using field with large range in tissue, i.e. in
      prostate cancer, using a Monte Carlo (MC) simulation system. METHODS: Previously
      treated prostate cancer cases were randomly selected from our patient database.
      All patients received the same dose prescription of 50Gy (25 fractions) to
      planning treatment volume including the seminal vesicles (PTV1), followed by 28Gy
      (14 fractions) boost to the prostate gland only (PTV2). Patient and beam geometry
      were imported to our MC simulation platform (TOPAS - TOol for PArticle
      Simulation) and the dose of each individual beam, as well as their weighted sum,
      were calculated and compared to pencil beam algorithm-based calculation from the
      clinical treatment planning system (XiO). RESULTS: Preliminary results from four
      patient cases show overall good agreement between the pencil beam and MC
      calculations. However, a small but systematic overestimation of the dose, as
      calculated by the pencil beam calculation algorithm, was noticed for the target
      structures (<2% difference in D95 for PTV1 and PTV2), compared to the MC
      calculation. The inverse was observed for the OARs (rectum and bladder) for which
      the dose seems to be somewhat underestimated by the pencil beam calculation
      algorithm (up to 3.75% difference in the volume covered by the 70Gy and 75Gy
      isodose lines). Furthermore, systematic difference in the range calculation was
      noticed: the pencil beam calculation algorithm results in larger proton range, in
      the order of 3-4mm, compared to the MC calculations for all beams and patients
      studied. This can be attributed to the bone anatomy in the path of the beams
      (femoral heads). CONCLUSIONS: Routine MC dose calculation has the potential to
      improve delivery accuracy in proton therapy of prostate cancer and influence the
      analysis of currently ongoing clinical trials of protons versus IMRT. Funded by
      NIH/NCI R01 CA140735.

PMID- 28517457
TI  - SU-E-T-477: Influence of Eye Size on Radiation Absorbed Dose Delivered to Non-
      Targeted Tissues during Stereotactic Radiosurgery for Age-Related Macular
      Degeneration.
AB  - PURPOSE: This work determines how variations in eye size will influence the
      radiation absorbed dose delivered to non-targeted tissues within the eye during
      stereotactic radiosurgery of age-related macular degeneration (AMD) using the
      IRayTM treatment. METHODS: Stylized models of the eye were created with axial
      lengths of 20, 22, 24, 26, and 28mm. Each model was based upon the reference eye
      model from NCRP Report 130 and then scaled appropriately for each axial length.
      Models were incorporated with MCNPX radiation transport code in order to simulate
      the three beam IRayTM delivery system. Simulation results were assessed for both
      the mean absorbed dose and dose-volume histograms (DVH) for both target (macula)
      and non- targeted eye tissues, including the lens, retina, central retinal
      artery, and optic nerve. RESULTS: For each of the three beams, an average dose of
      8Gy was delivered to the macula resulting in a total average dose of 24Gy for
      each eye model. The lens of the eye received a total average dose ranging from
      146 to 189mGy, with the larger doses occurring in the smaller eye models since
      the beams traverse through the sciera closer to the limbus. The distal tip
      (1.5mm) of the central retinal artery received a total average dose ranging from
      499 to 567mGy, with the larger doses occurring in the larger eye models due to
      increased scatter resulting from longer tissue path length to the nominal target.
      The optic nerve received a total average dose ranging from 207 to 225mGy, with
      the larger doses occurring in the smaller eye models. CONCLUSIONS: The small
      variation in dose to the lens, central retinal artery, and optic nerve suggests
      that eye size does not significantly affect radiation dose to non-targeted eye
      tissues. This work was sponsored by Oraya Therapeutics.

PMID- 28517458
TI  - SU-E-T-448: Switch Patients between Collimation Systems for CyberKnife Treatment
      Feasibility Study.
AB  - PURPOSE: There are two collimation systems associated with the CyberKnife system,
      the fixed cone collimator and the Iris collimator. The Iris collimator is used
      more frequently because of its superior flexibility. However, sometimes
      treatments have to be canceled or postponed due to Iris collimator mechanical
      failures. The purpose of this study is to investigate the feasibility of
      switching collimation systems without replanning. METHODS: We first performed
      Monte Carlo simulations on 10 clinical cases using the Iris collimator and the
      fixed cone collimator. The conformality index (CI), target volume coverage and
      the maximum, minimum and mean doses to the critical structures from the iris and
      fixed plans were compared to determine the feasibility of switching between
      collimator types without replanning. RESULTS: Our results showed that the two
      types of collimators deliver similar dose distributions. The average target doses
      for the fixed plans were 1% to 6% higher than those for the Iris plans. The
      average CI for the fixed plans was 1.36 compared to 1.28 for the Iris plans.
      Thus, we adjusted the Iris sizes with a scale factor of 1.024 to achieve a better
      dose match with the fixed collimators. Doses for the 10 cases were then
      recalculated. Once this correction was made, the difference between the average
      target doses for the two collimator plans was reduced to less than 2% and the CIs
      became almost identical. CONCLUSIONS: Small target dose differences were found
      between plans using different collimation systems, which may be compensated for
      by adjusting the Iris collimator sizes to ensure similar dose distributions. The
      differences in the doses to the critical structures between the collimation
      systems were insignificant. After adjusting the Iris collimator sizes and re
      commissioning the planning system, patients can be safely switched from the Iris
      collimator to the fixed cone collimator without replanning.

PMID- 28517456
TI  - SU-E-T-466: TCP and NTCP: Is That All?
AB  - PURPOSE: Concerns about the secondary cancer risks associated to the peripheral
      neutron and photon contamination in photon modern radiotherapy (RT) techniques
      (e.g., Intensity Modulated RT -IMRT- or Intensity Modulated Arc Therapy -IMAT)
      have been widely raised. Benefits in terms of better tumor coverage have to be
      balanced against the drawbacks of poorer organ at risk sparing and secondary
      cancer risk in order to make the decision on the optimum treatment technique. The
      aim of this study was to develop a tool which estimates treatment success taking
      into consideration the neutron secondary cancer probability. METHODS: A
      methodology and benchmark dataset for radiotherapy real time assessment of
      patient neutron dose and application to a novel digital detector (DD) has been
      carried out (submitted to PMB, 2011). Our DD provides real time neutron
      equivalent dose distribution in relevant organs along the patient. This
      information, together with TCP and NTCP estimated from the DVH of target and
      organs at risks, respectively, have been built into a general biological model
      which allows us to evaluate the success of the treatments (SA!nchez-Nieto et al.,
      ESTRO meeting 2012). This model has been applied to make estimation of treatment
      success in a variety of treatment techniques (3DCRT, forward and inverse IMRT,
      RapidArc, Volumetric Modulated Arc Therapy and Helical Tomotherapy) to low and
      high energy. RESULTS: MU-demanding techniques at high energies were able to
      deliver treatment plans with the highest complicated-free tumour control.
      Nevertheless, neutron peripheral dose must be taken into consideration as the
      associated risk could be of the same order of magnitude than the usually
      considered NTCPs. CONCLUSIONS: The methodology developed to provide an online
      organ neutron peripheral dose can be successfully combined with biological models
      to make predictions on treatment success taking into consideration secondary
      cancer risks.

PMID- 28517459
TI  - SU-E-T-488: Dose Calculation Model Using the Simplified Monte Carlo Method with
      an Initial Beam Model Adapted to a Beam-Wobbling System.
AB  - PURPOSE: We have developed an accurate dose calculation model based on a
      simplified Monte Carlo (SMC) method adapted to a beam-wobbling delivery system at
      National Cancer Center Hospital East (NCCHE). We used an initial beam model
      specific to the beam-wobbling system to reproduce accurately different dose
      distributions in two lateral directions (x- and y-directions) perpendicular to
      each other. METHODS: The SMC calculates a dose distribution by tracking
      individual protons. The SMC starts tracking protons at an entrance of a range
      compensator. Protons are generated in an initial phase space adapted to the
      wobbler system. Since two wobbling-magnets are located at separate places with
      different distances from the iso-center, different dose distributions are formed
      in x- and y-directions. We derived an initial phase space distribution for the
      beam-wobbling system using an analytical method. We used the SMC method with the
      initial beam model to calculate dose distributions accurately. To verify accuracy
      of the calculation method, we measured the dose distribution in a homogeneous
      phantom formed by 235 MeV protons passing through a L-shaped range compensator.
      We used a 2D-array of parallel-plate ionization chambers (2D Array seven29(r)) to
      measure dose distributions with a sampling period of 5 mm. RESULTS: The measured
      dose distribution in the x-direction was different from that in the y-direction.
      Our calculation model reproduces the measurement results well in both lateral
      directions. In addition, the calculation reproduced the dose increments in edge
      regions contributed by edge-scattered protons in collimator. It indicates the
      advantage of the SMC. CONCLUSIONS: A dose calculation model has been developed
      based on the simplified Monte Carlo method applied to a beam-wobbling system. By
      adapting the initial beam model to the wobbling system, the SMC method is found
      to reproduce observed different dose distributions in x- and y-directions well.

PMID- 28517460
TI  - SU-E-T-459: Radiobiological Evaluation of Implant Duration and Radionuclide
      Selection for COMS Eye Plaque Brachytherapy Using an Objective Function.
AB  - PURPOSE: The biologically effective dose (BED) of temporary brachytherapy
      treatments is a function of both chosen radionuclide (R) and implant duration
      (T). This study endeavored to evaluate BED delivered to the tumor volume and
      surrounding ocular structures as a function of plaque position (P), prescription
      dose, R, and T. METHODS: Plaque-heterogeneity- corrected dose distributions were
      generated with MCNP5 for the range of currently-available COMS plaques using low
      energy radionuclides. These physical dose distributions were imported into the
      Pinnacle3 TPS using the TG-43 hybrid technique and used to generate DVHs for a
      T=7d implant within a reference eye geometry at eight standard treatment
      positions. The Dale equation was employed to create biologically effective dose
      volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs.
      Isobiologically-effective prescription doses were calculated for T=5-0.01d, with
      BEDVHs subsequently generated for all ROIs using correspondingly reduced
      prescription doses. Objective functions were created to evaluate the BEDVHs as a
      function of R and T. RESULTS: Reducing T from 7 to 0.01d for a 10mm plaque
      produced an average BED benefit of 26%, 20%, and 17% for 103 Pd, 125 I, and 131
      Cs, respectively, for all P; 16mm and 22mm plaque results were more position
      dependent. 103 Pd produced a 16-35% BED benefit over 125 I, whereas 131 Cs
      produced a 3-7% BED detriment, independent of P, T, and plaque size.
      Additionally, corresponding OAR physical doses were lowest using 103 Pd in all
      circumstances. CONCLUSIONS: Shorter implant durations may correlate with more
      favorable outcomes vs. 7d implants for small and medium lesions. T may be safely
      reduced if the prescription dose is appropriately diminished. 103 Pd offers a
      substantial 16- 35% radiobiological benefit over 125 I and 131 Cs irrespective of
      P, T, and tumor size. The objective functions used in this study can be applied
      to temporary or permanent brachytherapy implants for a variety of disease sites.

PMID- 28517461
TI  - SU-E-T-499: Validation of the Varian Generic Phase Space Files for Monte Carlo
      Calculations of Dose Distributions for the TrueBeam Linac Head.
AB  - PURPOSE: To validate the generic phase space files for Varian TrueBeam linac head
      simulations. METHODS: The generic phase space files include the simulation
      results of 6MV, 10MV, 6MV FFF, and 10MV FFF (flattening-filter free) operating
      modes of TrueBeam for patient-independent linac head components. Using the
      generic phase space files as the radiation sources, the BEAMnrc Monte Carlo codes
      are used to simulate the patient-dependent parts of the TrueBeam linac and the
      resulting phase space files are generated at a plane just before entering a water
      phantom for 4 different field sizes (5*5, 10*10, 20*20, and 40*40 cm2 ). Dose
      distributions are calculated by DOSXYZnrc in the water phantom of size 50*50*40
      cm3 . The percentage-depth-dose (PDD) curves and lateral dose profiles at three
      different depths (dmax, 10cm, 20cm) are obtained. Comprehensive comparisons have
      been made for a total of 64 dose profiles (including PDDs) between the Monte
      Carlo calculations and the measured data. The gamma index analysis is performed
      for all the comparisons. RESULTS: The matching of the calculated dose
      distributions to the measured ones is analyzed by the gamma index method with a
      criterion of 2% dose tolerance and 2 mm distance-to-agreement. Of the 64
      comparisons, the minimum gamma index passing rate is at least 92%, after taking
      into account the statistical nature of the Monte Carlo calculated dose values.
      Despite the existence of latent variance of phase space files, the phantom dose
      calculation uncertainty can be less than 1% for field sizes as small as 5*5 cm2 .
      The computing time saved by using phase space files could be a factor of 5-10.
      CONCLUSIONS: The Varian generic phase space files are accurate and efficient
      radiation sources for Monte Carlo calculations of radiation dose distributions
      for TrueBeam linac head. This work was supported in part by Varian Medical
      Systems and the NIH (1R01 CA104205 and 1R21 CA153587).

PMID- 28517462
TI  - SU-E-T-470: Comparison of Proton Treatment Planning and Monte Carlo Calculation
      Using TOPAS for Liver Cancer.
AB  - PURPOSE: To compare Monte Carlo (MC) calculated and planned dose distributions
      (pencil beam algorithm) for patients with liver cancer treated with proton
      radiation therapy. METHODS: Six patients with unresectable Hepatocellular
      carcinoma were chosen from the institutional protocol list. We applied the newly
      developed TOPAS (Tool for Particle Simulation) Monte Carlo (MC) tool and an in
      house (mcauto) program, which connects the planning system with the MC. Two
      beams, typically right lateral (RL) and anterior-posterior (AP), were simulated
      for each patient with a total prescribed dose of 58 Gy. The calculated absolute
      dose was determined by separately simulating an SOBP dose in a water phantom for
      normalization to the prescription dose. The difference between MC and planned
      dose were calculated and Dose Volume Histograms (DVHs) for the critical organs
      with non-negligible dose (whole liver, heart, small and large bowel and chest
      wall) were analyzed. RESULTS: The resulting dose distributions were in quite good
      agreement. The main discrepancy in all cases was observed in the lateral
      penumbrae. These discrepancies can mainly result from the range compensator
      gradient and tissue composition. The Dose Volume Histograms (DVHs) also presented
      good agreement between doses for the CTV as well as all the OARs. The difference
      in D95 ranged from 0.7-1.5 Gy that is translated to 1.3-2.5% of the prescribed
      dose. CONCLUSIONS: TOPAS Monte Carlo tool presented an efficient and accurate
      method for dose calculation in liver and to validate clinical treatment planning.
      Discrepancies with doses calculated using the pencil beam algorithm were seen but
      were generally quite small.

PMID- 28517463
TI  - SU-E-T-461: Fractionation Schedule Optimization for Lung Cancer Treatments Using
      Radiobiological and Dose Distribution Characteristics.
AB  - PURPOSE: Lung cancer radiotherapy treatments employ a wide variety of
      fractionation protocols. The choice among protocols mostly depends on the size of
      the target volume (GTV or ITV) and the volume of normal tissue receiving a
      critical dose. Rigorous mathematical criteria for normal tissue (NT) dose
      distributions were derived to determine the type of dose per fraction schedule
      that maximizes linear-quadratic tumor effect. METHODS: Selecting the individual
      doses per fraction that maximize a linear-quadratic effect in the tumor while
      constraining the normal tissue complication probability according to the Lyman
      Kutcher-Burman model leads to an optimization problem. For time-independent
      parameters, the solution is always an equal dose per fraction schedule; depending
      on parameter values, two different class solutions are suggested: minimal number
      of fractions clinically realized with hypo-fractionation, or minimizing dose per
      fraction clinically realized with standard- or hyper-fractionation. The value of
      a single scale-free "bifurcation" number, derived from the DVH of the NT dose
      distribution suggests which solution is preferred for a given plan with respect
      to a given normal tissue. The clinical relevance of the bifurcation number in
      selecting fractionation schemes was tested for 30 patients previously treated for
      non-small-cell lung cancer according to various fractionation protocols. RESULTS:
      The bifurcation numbers for both lung and esophagus were a good classifier for
      the hypofractionated and the conventional fractionation groups. The variability
      of the numbers within patients of the conventional fractionation group was much
      smaller than the variability of the treated ITV volumes or the ITV to lung volume
      ratios. The prescribed fractionations were also consisted with the currently
      accepted alpha-beta values for tumor (10) and radiation-induced pneumonities in
      the lung (4). CONCLUSIONS: Model-based criteria such as the bifurcation number
      may replace the more empirical volume criteria to decide the optimal
      fractionation protocol once the dose distribution has been optimized.

PMID- 28517465
TI  - SU-E-T-443: The Dosmetic Difference of RapidArc Plans in Radiotherapy of Multiple
      Hepatic Malignancy Applying 6MV and 15MV X-Ray.
AB  - PURPOSE: To investigate the dosmetric difference in the application of RapidArc
      using 6MV X and 15MVX X-ray for radiotherapy of multiple hepatic malignancy.
      METHODS: 12 cases with multiple hepatic tumors (primary 5 cases or secondary 7
      cases) were selected. All patients underwent the three dimensional CT simulation
      in free breathing. For each patient, RapidArc plans with single or two 358
      degrees  arcs using 6MV X or 15MVX-ray were designed respectively, the
      prescription dose was 2Gy/Fractionx25 Fractions. The dosimetric differences were
      compared among RapidArc plans. RESULTS: All of RapidArc plans can meet the
      clinical requirement. There were no significant difference were found in the
      conformity index (CI), homogeneity index (HI), the maximum dose and the minimum
      dose of PTV among RapidArc plans(P>0.05), and all the CI can get to 0.91 and HI
      can get to 0.88. In the RapidArc plans with two 358 degrees  arcs, the V5,V10,V15
      of normal liver were higher than with single arc, while V20, V25, V30, V35, V40
      were lower than with single arc. The radiation dose of normal liver, stomach,
      duodenum and spinal cord differed no significantly among different plans(P>0.05).
      The monitor units of RapidArc plans using 6MV X- ray increased 12% compared to
      15MV averagely. CONCLUSIONS: The 6MV X-ray would be selected chiefly in the
      radiotherapy of multiple haptic tumor using RapidArc with single or two whole
      arcs.

PMID- 28517464
TI  - SU-E-T-472: Characterization of the Very High Energy Electrons, ISO - 250 MeV
      (VHEE) Beam Generated by ALPHA-X Laser Wakefield Accelerator Beam Line for
      Utilization in Monte Carlo Simulation for Biomedical Experiment Planning.
AB  - PURPOSE: Progress in the development of compact high-energy pulsed laser- plasma
      wakefield accelerators is opening up the potential for using Very High Energy
      Electron (VHEEs) beams in the range of 150 - 250 MeV for biomedical studies.
      Initial experiments using VHEE for this purpose have been carried out using the
      ALPHA-X laser-plasma wakefield accelerator beam line at the University of
      Strathclyde, Glasgow, UK. The purpose of this investigation is to use Monte Carlo
      simulations to plan experiments and compare with characterization of the
      interaction of the VHEE beam using a dosimeter. METHODS: An experiment using the
      VHEE beam to irradiate a muscle-equivalent BANG polymer gel dosimeter has been
      carried out. Simulations have been used to prepare for the experiments. These
      were undertaken using the expected average energy for a pulse set and an energy
      spread approximated by Gaussian distribution. The model was implemented in FLUKA
      Monte Carlo code with follow up modeling using the Geant4 toolkit. The results
      have been compared with 1mm3 voxel laser CT based measurements of the dose
      deposited in the BANG dosimeter and with measurement of the induced
      radioactivity. RESULTS: The results of the measured dose from induced
      radioactivity have been compared with data from the FLUKA simulations. The beam
      model based on an average energy of particles in irradiation gives an acceptable
      estimate of the induced radioactivity and the dose deposited in the BANG
      dosimeter. Comparison with the dosimeter scanned profiles shows that the
      structure of the spectra of VHEE beams in the experiment and secondary scattered
      particles in the beam line should be accounted for in any model. Such model
      description of the VHEE beam for the ALPHA-X beam line has been developed.
      CONCLUSIONS: Monte Carlo simulations using the FLUKA code is an efficient way to
      plan a VHEE experiment and analyze data from measurements.

PMID- 28517466
TI  - SU-E-T-483: Delay Treatment or Switch to Different Machines? Dosimetric Effect
      and Tumor Control Probability.
AB  - PURPOSE: If the Linac is unavailable during the IMRT treatment schedule, the
      patient can be switched to a different Linac or prostpond treatment until the
      origonal Linac is available. The resulting dosimetric difference is estimated and
      the compromise in the TCP is estimated for both scenarios. This work investigates
      the feasibility and rationale of switching patients between different
      accelerators for IMRT in contrast to prostponing the treatment. METHODS: We
      performed Monte Carlo simulations of photon beams from different Linac models and
      vendors. Prostate and head and neck treatment plans for Siemens Primus, Primart,
      Artiste and Varian-21Ex/IX accelerators are studied in this work. Dose
      distributions for given plans are recalculated using different beam data with the
      same nominal energy from different Linacs. We have compared DVHs, the maximum,
      the minimum and the mean dose to the target and critical structures due to
      switching accelerators. In the process of switching a treatment plan to a
      different accelerator, there are issues, such as optimum penumbra compensation,
      dose distribution at the boundary of target and critical structures and multileaf
      collimator (MLC) leaf width effects, needed to be considered and verified with
      measurements. In making the final decision whether to switch machines, the TCP
      based on a linear-quadratic model with time factor is considered. RESULTS: Two
      DVHs of two plans from Varian and Siemens models are delivered on different
      machines. Slight dose coverage differences have been observed. TCP estimation
      with both delayed and without delayed treatments is calculated. Undesired drop of
      TCP is observed with treatment gap. CONCLUSIONS: Based on the analyses done in
      this work, it is therapeutically more beneficial to switch a patient to a
      different machine than to postpone a treatment until the original machine is
      available, especially for fast growing tumors such as head and neck cancers.

PMID- 28517467
TI  - SU-E-T-454: Dosimetric Comparison between Pencil Beam and Monte Carlo Algorithms
      for SBRT Lung Treatment Using IPlan V4.1 TPS and CIRS Thorax Phantom.
AB  - PURPOSE: To compare measured and calculated doses using Pencil Beam (PB) and
      Monte Carlo (MC) algorithm on a CIRS thorax phantom for SBRT lung treatments.
      METHODS: A 6MV photon beam generated by a Primus linac with an Optifocus MLC
      (Siemens) was used. Dose calculation was done using iPlan v4.1.2 TPS (BrainLAB)
      by PB and MC (dose to water and dose to medium) algorithms. The commissioning of
      both algorithms was done reproducing experimental measurements in water. A CIRS
      thorax phantom was used to compare doses using a Farmer type ion chamber (PTW)
      and EDR2 radiographic films (KODAK). The ionization chamber, into a tissue
      equivalent insert, was placed in two position of lung tissue and was irradiated
      using three treatments plans. Axial dose distributions were measured for four
      treatments plans using conformal and IMRT technique. Dose distribution
      comparisons were done by dose profiles and gamma index (3%/3mm). RESULTS: For the
      studied beam configurations, ion chamber measurements shows that PB overestimate
      the dose up to 8.5%, whereas MC has a maximum variation of 1.6%. Dosimetric
      analysis using dose profiles shows that PB overestimates the dose in the region
      corresponding to the lung up to 16%. For axial dose distribution comparison the
      percentage of pixels with gamma index bigger than one for MC and PB was, plan 1:
      95.6% versus 87.4%, plan 2: 91.2% versus 77.6%, plan 3: 99.7% versus 93.1% and
      for plan 4: 98.8% versus 91.7%. It was confirmed that the lower dosimetric errors
      calculated applying MC algorithm appears when the spatial resolution and variance
      decrease at the expense of increased computation time. CONCLUSIONS: The agreement
      between measured and calculated doses, in a phantom with lung heterogeneities, is
      better with MC algorithm. PB algorithm overestimates the doses in lung tissue,
      which could have a clinical impact in SBRT lung treatments.

PMID- 28517468
TI  - SU-E-T-494: Variation of Mucosal Dose in Head-And-Neck Radiotherapy: A Phantom
      Study Using Monte Carlo Simulation.
AB  - PURPOSE: This phantom study investigated variations of mucosal dose on photon
      beam energy, beam angle, multi-beam configuration and mucosal thickness, when
      using small photon fields in head-and-neck radiotherapy. METHODS: Cylindrical
      mucosa phantoms with bone and air heterogeneities were created with mucosal
      thickness (normal tissue) equal to 1, 2 and 3 mm. For dosimetric comparison,
      corresponding homogeneous phantom with all heterogeneities replaced by normal
      tissue was also used. These phantoms were irradiated by photon beams with field
      size = 1 * 1 cm2 . Beam energies of 6 and 18 MV were used with beam angles varied
      to 0 degrees , 90 degrees  and 180 degrees . Moreover, multi-beam configurations
      of 2, 4 and 8 beams were used, and doses along the central-beam axis in the
      mucosal tissue were calculated using Monte Carlo simulations (EGSnrc code).
      RESULTS: For beam angle equal to 0 degrees , the mucosal surface doses decreased
      slightly with an increase of the mucosal thickness (1-3 mm), while the surface
      dose of the 6 MV photon beam was decreased more significantly than the 18 MV. For
      beam angle equal to 180 degrees , variation of muscosal surface dose with its
      thickness was found insignificant. For different multi-beam configurations, it
      was found that the variation of mucosal dose on its thickness became
      insignificant when the number of photon beams around the mucosa was increased. In
      addition, the change of mucosal dose due to the bone and air heterogeneities
      depended on the photon beam energy, beam angle and muscosal thickness.
      CONCLUSIONS: It is concluded that mucosal dose depends on variations of beam
      energy, beam angle, multi-beam configuration and mucosal thickness for small
      photon fields. The dosimetric information in this study should be considered in
      studying the mucosal complications in head-and-neck IMRT, so that an optimized
      treatment strategy to minimize mucosal complications can be developed. This study
      is supported by the Deana?TMs Fund Grant in the University of Toronto.

PMID- 28517469
TI  - SU-E-T-465: Exploring the Dosimetric and Tumor Control Consequences of Prostate
      Seed Loss and Migration.
AB  - PURPOSE: Once implanted, prostate brachytherapy seeds are vulnerable to loss and
      movement. A general estimation of these effects may be useful for making patient
      care decisions when seeds are lost after the post-implant scan. The goal of this
      work was to explore the dosimetric and radiobiological effects of the types of
      seed loss and migration common in prostate brachytherapy. METHODS: This study
      evaluates five patients. For each, three treatment plans were created using
      Iodine-125, Palladium-103 and Cesium-131. The three seeds closest to the urethra
      were identified and modeled as seeds lost through the urethra. The three seeds
      closest to the exterior of prostatic capsule were identified and modeled as those
      lost from the prostate periphery. The seed locations and organ contours were
      exported from Prowess and used by in-house software to perform the dosimetric and
      radiobiological evaluation. The radiobiological evaluation was based on the
      linear-quadratic model. Seed loss was simulated by removing 1, 2 or 3 seeds near
      the urethra 0, 2 or 4 days after the implant or removing seeds near the exterior
      of the prostate 14, 21 or 28 days after the implant. RESULTS: Loss of 1, 2 or 3
      seeds through the urethra resulted in D90 reduction of 2%, 5% and 7% loss
      respectively. Due to delayed loss of peripheral seeds, effects were less severe
      than for loss through the urethra. However, while the dose reduction is modest
      for multiple lost seeds, the reduction in tumor control probability was minimal.
      CONCLUSIONS: The goal of this work was to explore the dosimetric and
      radiobiological effects of the types of seed loss and migration commonly seen in
      prostate brachytherapy. The results presented show that loss of multiple seeds
      can cause a substantial reduction of D90 coverage. However, the dose reduction
      was not seen to significantly reduce tumor control probability.

PMID- 28517470
TI  - SU-E-T-476: GPU-Based Monte Carlo Radiotherapy Dose Calculation Using Phase-
      Space Sources.
AB  - PURPOSE: To design an efficient method for utilizing phase-space source models in
      the GPU-based Monte Carlo (MC) dose calculation engine gDPM. METHODS: In GPU
      based MC algorithms, particles are transported in parallel on different threads.
      Particles of different types and energies can require significantly different
      execution times. This can cause "thread divergence" and lower efficiency when
      source particles are read sequentially from a phase-space file. We have developed
      a strategy for utilizing phase- space files in a GPU compatible manner whereby
      the particles are grouped into phase-space-lets (PSLs) by type, energy, and
      location in the phase- space plane. This allows for dose calculations using only
      particles inside the field opening defined by the secondary collimators. For
      validation, the gDPM PSL implementation is compared with DOSXYZnrc using a
      BEAMnrc phase-space source model as input. RESULTS: Two phase-spaces were
      generated using a BEAMnrc head model of a 6MV Varian Clinac 21EX, one above the
      upper jaws used to generate PSLs for gDPM and the other below the lower jaws used
      for DOSXYZnrc dose calculation. Profiles and depth dose curves for a variety of
      field sizes were generated in a water phantom. The agreement between gDPM and
      DOSXYZnrc is within 2% for all field sizes. For the 10 cm * 10 cm field, the
      calculation times of 650 million histories were 147 CPU hours and 54 GPU seconds
      for DOSXYZnrc and gDPM, respectively. In addition, we have tested the gDPM PSL
      implementation for dose calculation in a realistic 7-field IMRT tongue treatment
      plan. The calculation times were 59 CPU-hours and 66 GPU- seconds for DOSXYZnrc
      and gDPM for 485 million histories, respectively. Gamma pass rate for the two
      dose distributions was 99.54% for 3 mm/3% criteria within the 10% isodose.
      CONCLUSIONS: Methods for the efficient use of phase-space sources for GPU-based
      MC dose calculations have been developed.

PMID- 28517471
TI  - SU-E-T-447: Evaluation of the Anisotropic Analytical Algorithm (AAA)
      Heterogeneity Correction Dose Calculation in Flattened and Flattening- Filter
      Free (FFF) Beams for High Energy X-Ray Beams Using the Radiological Physics
      Center (RPC) Lung Phantom.
AB  - PURPOSE: Compare the accuracy of AAA heterogeneity corrected dose calculation
      algorithm for high energy x-ray beams (>10 MV) for flattened and FFF beams using
      RPC anthropomorphic thorax phantom. METHODS: Six static beam SBRT treatment plans
      were created using the Varian Eclipse treatment planning system (TPS) AAA
      v.8.9.08 heterogeneity correction algorithm. Two flattened beam plans (6 MV and
      18 MV) and four other plans (6 MV, 6 MV FFF, 10 MV FFF and 15 MV) were delivered
      using a Clinac 21EX and TrueBeam STx, respectively. Prescription dose/coverage, 6
      Gy to 95% PTV, and constraints were the same for all plans. The phantom contained
      radiochromic films in the 3 major planes and TLDs in the heart, spine, and tumor.
      Point doses and 2D dose distributions were exported from the Eclipse TPS and
      compared with the measured doses. The gamma index analysis evaluation criteria of
      +/-5% dose to agreement and 3 mm distance to agreement was used. RESULTS: TLD to
      TPS tumor point dose ratios were 0.971+/-0.006(6MV) and 0.957+/-0.002(6MV),
      0.995+/-0.005(15MV), 1.114+/-0.006(18MV), and 0.957+/-0.003(6MV FFF), 0.974+/
      0.011(10MV FFF) for the six plans. Using +/-5%/3mm gamma analysis criteria, the
      average passing rates for all three films were 96.3% and 95.5%, 97.4%, 66.1%,
      93.7%, and 96.3% for the 6 MV, 6 MV, 15 MV, 18 MV, 6 MV FFF, and 10 MV FFF plans,
      respectively. Dose profiles were also evaluated. CONCLUSIONS: The current RPC
      credentialing criteria are: RPC/Inst. tumor dose ratio of 0.97+/-0.05 and 85% of
      the pixels in each film plane must pass a +/-5%/5mm gamma index analysis. These
      data demonstrate that the AAA heterogeneity correction dose calculation algorithm
      is accurate for photon energies in 6-15 MV range for flattened and FFF beams.
      Heterogeneity corrected dose calculations for photon energies >15 MV were not
      accurate. Work supported by grants CA10953 and CA81647 (NCI, DHHS).

PMID- 28517472
TI  - SU-E-T-487: Spatial Assessment of Dose Distributions for Patients with Lung
      Cancer Treated with Stereotactic Ablative Radiotherapy (SABR).
AB  - PURPOSE: We hypothesize that PTV margin dose is an important factor for local
      tumor control. We evaluated dose distributions for patients originally treated
      with pencil-beam (PB)-based plans and retrospectively calculated with Monte Carlo
      (MC) method, with emphasis on the spatial region between the ITV and PTV (PTV
      margin), where the largest dose differences were expected. METHODS: Forty-six
      stage I-II lung cancer patients with 51 lesions treated with SABR were
      retrospectively analyzed (23 central and 28 peripheral tumors). All patients
      received 4DCT imaging, and an ITV was generated from the maximum intensity
      projection and subsequent review of four 4DCT phases. An isotropic 3mm ITV-to-PTV
      margin was used. The iPlan TPS was used to generate the original treatment plans
      using PB-based heterogeneity correction. MC doses were recalculated using the
      same MUs as in the PB plan. Dose distributions for the ITV, PTV-margin, and PTV
      were analyzed using generalized equivalent uniform dose (gEUD) with a = - 20.
      Student's paired t-test elucidated differences between PB and MC-based gEUD and
      the two different tumor locations. RESULTS: Mean ITV and PTV volumes were 24.2 cc
      (range: 2.2 to 99.3 cc) and 50.4 cc (range: 6.4 to 229.7 cc), respectively. The
      mean gEUDs of ITV, PTV-margin and PTV, normalized to PB-based 100% isodose were
      1.02+/-0.04, 1.01+/-0.04 and 1.01+/-0.04 for PB-based plans, compared to 0.94+/
      0.06, 0.88+/-0.08 and 0.90+/-0.08 (all p<0.05) for MC-based plans. The maximum
      overestimations with the PB algorithm in the PTV-margin average dose were 10.4%
      and 19.6% (p < 0.05) for peripheral tumor cases and central tumor cases,
      respectively. CONCLUSIONS: PB-based dose distributions showed the highest dose
      overestimation (relative to MC) in the PTV-margin spatial region. Analysis of
      spatial dose differences is an important precursor toward assessment of patterns
      of-local failure, to be investigated in future work to explore possible
      association between dose and regions of failure. Acknowledgement: supported in
      part by grants from NIH R01 CA106770 and from Varian Medical Systems.

PMID- 28517473
TI  - SU-E-T-458: Radiobiological Comparison of Single and Dual-Isotope Prostate Seed
      Implants.
AB  - PURPOSE: Several isotopes are available for low dose-rate brachytherapy of the
      prostate. Currently, most implants use a single isotope. However, the use of dual
      isotope implants may yield an advantageous combination of characteristics such as
      half-life and relative biological effectiveness. However, the use of dual-isotope
      implants complicates treatment planning and quality assurance. Do the benefits of
      dual-isotope implants outweigh the added difficulty? The goal of this work was to
      use a linear-quadratic model to compare single and dual-isotope implants.
      METHODS: Ten patients were evaluated in this study. For each patient, six
      treatment plans were created with single or dual-isotope combinations of 1251,
      103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were
      contoured by a physician. The biologically effective dose was used to determine
      the tumor control probability and normal tissue complication probabilities for
      each plan. Each plan was evaluated using favorable, intermediate and unfavorable
      radiobiological parameters. The results of the radiobiological analysis were used
      to compare the single and dual-isotope treatment plans. RESULTS: Iodine-125 only
      implants were seen to be most affected by changes in tumor aggressiveness.
      Significant differences in organ response probabilities were seen at common dose
      levels. It was recognized that these differences were likely a result of
      suboptimal initial seed strengths. After adjusting the initial seed strength to
      maximize complication-free tumor control the differences between isotope
      combinations were minimal. This result was true even for unfavorable tumors.
      CONCLUSIONS: The objective of this work was to perform a radiobiologically based
      comparison of single and dual-isotope prostate seed implant plans. For all
      isotope combinations, the plans were improved by varying the initial seed
      strength. For the minimally-optimized treatment plans, no substantial differences
      in predicted treatment outcomes were seen among the different isotope
      combinations.

PMID- 28517474
TI  - SU-E-T-498: A Preliminary Monte Carlo Simulation Study of the Varian TrueBeam
      Linear Accelerator.
AB  - PURPOSE: To benchmark the quality of Monte Carlo simulation results with the
      commissioning data for a Varian TrueBeam accelerator. METHODS: IAEA phase space
      files of a 6MV TrueBeam accelerator provided by Varian were implemented using
      GEANT4 Monte Carlo code. The present application consisted of upper and lower
      jaws and a cubic water phantom of 0.125 cubic meters in volume. Both radial and
      transverse dose profiles (in 5 different depths) and a central axis percentage
      depth dose (PDD) curve were recorded in the phantom. Field sizes of as small as
      4*4 cm2 and as large as 30*30 cm2 were simulated with 2.0E9 incident particles
      each. The results were then compared with our commissioning data performed in a
      Wellhoffer Blue Phantom with a 0.13cc ion-chamber and a 0.8*0.8mm diode. RESULTS:
      The GEANT4 simulated PDD curve compared favorably within ~2% against the measured
      ion-chamber PDD for all field sizes and against the measured diode PDD for all
      fields less then 20*20cm2 . The simulated in-plane and cross-plane profiles
      compared well within 2 mm at the 50% level against the measured profiles for all
      field sizes. CONCLUSIONS: These results demonstrate the feasibility of utilizing
      Monte-Carlo simulated beam data in the commissioning of a linear accelerator. The
      increasing speed and capability of the desktop computer will Result in the
      adoption of Monte- Carlo techniques for dosimetric calculations.

PMID- 28517475
TI  - SU-E-T-469: The Effects of Patient Anatomy and Parallel Magnetic Fields on
      Beamlet Dose Distributions.
AB  - PURPOSE: Beamlets are generated in a patient geometry in the presence of a
      magnetic field to investigate the effects of tissue density and magnetic field on
      beamlet dose distributions, which is important for the optimization of photon
      fluence to be delivered by a linac-MR system. METHODS: 50*50 mm2 fields were
      placed with isocenter in the middle of a patient's right lung. Each treatment
      field was decomposed into 100 beamlets (each 5*5 mm2 ). BEAMnrc scored the
      particle phase space at 100.2 cm from the source in the linac-MR geometry
      (isocentre at 126 cm) with parallel magnetic fields of 0, 0.56, and 3T. DOSXYZnrc
      was modified to score the energy deposited by particles from this phase space as
      a function of the beamlet the particle passed through. The calculation volume of
      70*46*64 voxels encompassed the patient with a voxel size of 3*3*3 mm3 . Each
      beamlet was normalized to the dose calculated to a 3*3*3 mm3 voxel with isocenter
      at 5cm depth in a flat water tank without a magnetic field. RESULTS: Beamlet
      files were calculated on Western Canada's high performance computing cluster
      (Westgrid) using 100 processors, enabling simulation of 109 histories in less
      than 3 hours. The resulting files, which contained 3D dose distributions for all
      100 beamlets, were 81 MB per field. The Monte Carlo uncertainty was also stored.
      The gyroradii for 1 MeV electron traversing field lines at 20 degrees are 2.9mm
      and 0.5mm for 0.56 and 3T fields respectively. The 0.56T parallel magnetic field
      has a small effect compared to the distortion of the beamlet introduced by the
      presence of lung. CONCLUSIONS: The effect of tissue heterogeneities is more
      significant than the effect of a 0.56T parallel magnetic field. A 3T field
      refocuses the dose in lung to the beamlet path and significantly reduces the
      lateral electron scatter.

PMID- 28517476
TI  - SU-E-T-480: Updating the Planar Patterson-Parker Table Using the TG-43U1
      Recommended Dosimetric Parameters.
AB  - PURPOSE: In this project, the Patterson-Parker Table has been updated for Cs-137
      and Ir-192 sources using their recent TG-43U1 dosimetric data. In addition, dose
      uniformity for the different loading schemes as a function of implant area has
      been verified. METHODS: The updated Paterson-Parker tables have been generated
      for planar implants with Cs-137 and Ir-192 sources using their published TG-43U1
      dosimetric parameters. Accuracies of the updated tables were examined by two
      independent methods, namely, Monte Carlo simulation technique and using a
      commercially available treatment planning system. In addition to the dose values
      along the central axis of the implant, dose profiles along two orthogonal
      directions have been evaluated for selection of the optimum radioactivity
      distribution in each implant geometry. RESULTS: The results of these
      investigations show that for the same implant size the mg.hr required for
      delivery of a given dose with Cs-137 is not identical to that of Ir-192. In
      addition, some differences between the updated Table and the published Paterson
      Parkers Tables have been observed. Independent Monte Carlo simulations and
      treatment planning data for multi-seed implant indicated the accuracy (less than
      +/-5%) of the updated Table. CONCLUSIONS: This work gives complete updated
      Paterson-Parker Tables for two of the commonly utilized brachytherapy sources.
      For delivery of a given dose, significant differences (approximately 35%) have
      been observed between the traditional Paterson-Parker Table and the updated
      Tables. These differences are attributed to the differences of tissue
      attenuation, 2D anisotropy functions as well as the availability of the new
      source dosimetry.

PMID- 28517477
TI  - SU-E-T-471: Beam Properties of an In-Room Proton Therapy Accelerator.
AB  - PURPOSE: To quantify basic beam properties of the first gantry-mounted proton
      therapy accelerator, situated in the treatment room and delivering beam to the
      patient without any intermediate bending magnets. METHODS: Monte Carlo
      simulations for prototype beamlines of the Mevion S250TM proton therapy system
      were performed using MCNPX. For each configuration, open profiles in air were
      determined at 3 different positions for 3 range settings (216 profiles).
      Similarly, half-beam-blocked profiles were determined for the same settings (216
      profiles). Additionally, beam axis fluence profiles in air were determined for 3
      range settings (72 profiles). Finally, Bragg peak depth-dose curves in water were
      determined for 3 range settings (72 profiles). Using these 576 profiles, several
      beamline parameters were determined for each proton range and configuration,
      including virtual SAD, effective source size, and effective SAD. Additionally,
      Bortfeld's analytic approximation of the Bragg curve was fit to each depth-dose
      curve to determine R0, sigma and epsilon. The 72 values determined for each
      parameter were compared within each configuration and across all configurations.
      RESULTS: Within any configuration, the change in range was too small (=2.5 cm) to
      have a large effect on any of the extracted parameters. Comparing parameters
      among configurations revealed smooth trends. These parameters were then fit as a
      function of range. CONCLUSIONS: The simplicity of this system results in beams
      with greater similarity among configurations as compared to other proton therapy
      systems. Because a beam with fixed initial energy is degraded only by tissue
      equivalent materials, range straggling and beam divergence are nearly constant
      across all beamline configurations. Beam parameters change smoothly as functions
      of proton range, with no major discontinuities between configurations. This
      suggests that the entire machine may be fully and accurately characterized in a
      treatment planning system by fewer measurements than would normally be required.

PMID- 28517479
TI  - SU-E-T-482: A More Accurate Bare 12 5I Spectrum.
AB  - PURPOSE: To compare measured energy spectra of 125 I brachytherapy seeds with
      Monte Carlo calculated energy spectra when using the bare 125 I energy spectrum
      recommended by TG43 and the one presented in NCRP Report 58 and to determine the
      impact of these different spectra on the calculation of the dose rate constant.
      METHODS: The energy spectrum, absorbed dose at 1 cm on the bisector and air kerma
      strength of 10 different 125 I seeds were calculated using the EGSnrc BrachyDose
      Monte Carlo code. Energy bin width was 0.2 keV. The simulations were done with
      the bare 125 I energy spectrum recommended by TG43 or NCRP Report 58. Statistical
      uncertainties for the energy spectra were 0.02% and 0.1% or less for the other
      clinical parameters. Results are compared with published measuredvalues. RESULTS:
      There is close agreement between the measured and calculated branching ratio
      generated by 125 I seeds when simulated using the spectrum presented in NCRP58.
      However, for all seeds a 7% lower value is observed in the 31 keV peak when using
      data suggested by TG43. On the other hand, differences in the average energy, air
      kerma, absorbed dose and dose rate constant are undetectable (less than
      statistical uncertainty, <0.1%) when performed with either spectrum. CONCLUSIONS:
      For dosimetric parameter calculations, the bare 125 I energy spectra presented in
      TG43 and NCRP58 produce indistinguishable results. However, for branching ratio
      investigation purposes, there is a clear difference in the 31 keV peak between
      values obtained using the different 125 I bare energy spectra. Measured 125 I
      branching ratios are in close agreement with those calculated using the bare 125
      I energy spectrum presented in NCRP58. Reassessment of the bare 125 I energy
      spectrum recommended in TG43 is suggested.

PMID- 28517478
TI  - SU-E-T-442: Assessing Vertex Beam with its Dosimetric Relevance for Intracranial
      Tumours: A Computational Exploration.
AB  - PURPOSE: To assess the selection of the minimal vertex beam angle for the
      avoidance of organs at risk (OARs) in radiotherapy planning of brain tumors.
      METHODS: Seventy patients with intracranial tumors were studied. Three field
      conformal plans with co-planar or non co-planar beam arrangements with an
      anterior vertex beam were used. Two methods were studied for determining the
      vertex angle for avoidance of eye as organ at risk. In the standard technique,
      the beam's eye view (BEV) was used to determine need of vertex beam. For the
      vertex beam, the angle was approximated to avoid eyes. In the second method, the
      angle from the baseplate to the posterior surface of the head and the angle from
      the posterior surface of the head to the inferior-most extent of the head were
      measured from sagital view. The minimum vertex angle required was calculated as
      the complement of the sum of these angles. The dose volume histogram parameters
      were maintained. RESULTS: Depending on the spatial location of the planning
      target volume with reference to the eyes, patients were classified into 4 types:
      no overlap; overlap with eye anteriorly; overlap with eye posteriorly, overlap
      with eye anteriorly and posteriorly. No additional angulation, positive vertex
      and negative vertex angles were needed for type 1, 2 and 3 respectively. The
      angle subtended by the isocenter to the neck rest apex was the required vertex
      angle for type 4. Of the 36 type 2, 3 and 4 patients the planned vertex angle was
      more than the calculated vertex angle by over 5 degrees in 10 patients, and less
      by over 5 degrees in 4 patients. CONCLUSIONS: A simple method for deriving the
      minimal vertex beam angle for OAR avoidance in radiotherapy planning of
      intracranial tumors was described and validated.

PMID- 28517480
TI  - SU-E-T-453: Optimization of Dose Gradient for Gamma Knife Radiosurgery.
AB  - PURPOSE: The goals of stereotactic radiosurgery (SRS) are the ablation of target
      tissue and sparing of critical normal tissue. We develop tools to aid in the
      selection of collimation and prescription (Rx) isodose line to optimize the dose
      gradient for single isocenter intracranial stereotactic radiosurgery (SRS) with
      GammaKnife 4C utilizing the updated physics data in GammaPlan v10.1. METHODS:
      Single isocenter intracranial SRS plans were created to treat the center of a
      solid water anthropomorphism head phantom for each GammaKnife collimator (4 mm, 8
      mm, 14 mm, and 18 mm). The dose gradient, defined as the difference of effective
      radii of spheres equal to half and full Rx volumes, and Rx treatment volume was
      analyzed for isodoses from 99% to 20% of Rx. RESULTS: The dosimetric data on Rx
      volume and dose gradient vs. Rx isodose for each collimator was compiled into an
      easy to read nomogram as well as plotted graphically. The 4, 8, 14, and 18 mm
      collimators have the sharpest dose gradient at the 64%, 70%, 76%, and 77% Rx
      isodose lines, respectively. This corresponds to treating 4.77 mm, 8.86 mm, 14.78
      mm, and 18.77 mm diameter targets with dose gradients radii of 1.06 mm, 1.63 mm,
      2.54 mm, and 3.17 mm, respectively. CONCLUSION: We analyzed the dosimetric data
      for the most recent version of GammaPlan treatment planning software to develop
      tools that when applied clinically will aid in the selection of a collimator and
      Rx isodose line for optimal dose gradient and target coverage for single
      isocenter intracranial SRS with GammaKnife 4C.

PMID- 28517481
TI  - SU-E-T-493: Accelerated Monte Carlo Methods for Photon Dosimetry Using a Dual-GPU
      System and CUDA.
AB  - PURPOSE: To develop a Graphics Processing Unit (GPU) based Monte Carlo (MC) code
      that accelerates dose calculations on a dual-GPU system. METHODS: We simulated a
      clinical case of prostate cancer treatment. A voxelized abdomen phantom derived
      from 120 CT slices was used containing 218*126*60 voxels, and a GE LightSpeed 16
      MDCT scanner was modeled. A CPU version of the MC code was first developed in C++
      and tested on Intel Xeon X5660 2.8GHz CPU, then it was translated into GPU
      version using CUDA C 4.1 and run on a dual Tesla m2 090 GPU system. The code was
      featured with automatic assignment of simulation task to multiple GPUs, as well
      as accurate calculation of energy- and material- dependent cross-sections.
      RESULTS: Double-precision floating point format was used for accuracy. Doses to
      the rectum, prostate, bladder and femoral heads were calculated. When running on
      a single GPU, the MC GPU code was found to be *19 times faster than the CPU code
      and *42 times faster than MCNPX. These speedup factors were doubled on the dual
      GPU system. The dose Result was benchmarked against MCNPX and a maximum
      difference of 1% was observed when the relative error is kept below 0.1%.
      CONCLUSIONS: A GPU-based MC code was developed for dose calculations using
      detailed patient and CT scanner models. Efficiency and accuracy were both
      guaranteed in this code. Scalability of the code was confirmed on the dual-GPU
      system.

PMID- 28517482
TI  - SU-E-T-464: Impact of the Treatment Margin on Tumor Control and Normal Tissue
      Complication for Prostate Treatment.
AB  - PURPOSE: To investigate the consequence of treatment margin reduction on normal
      tissue complication probability (NTCP) and tumor control probability (TCP) of
      prostate external beam treatment. METHODS: Intensity modulated rotational
      radiotherapy plans were generated for 10 prostate patients with 6 different
      posterior margin sizes from 5mm to 0. The prescription dose is 80Gy for 40
      treatment fractions. The dose distributions were recalculated with consideration
      of the intrafractional motion and the localization error. The statistical
      uncertainties of the intrafractional motion and the localization error were
      derived based on the motion tracking data recorded by the Calypso 4D localization
      system for a large patient population. The TCP and NTCP were calculated based on
      the dose volume histograms (DVH) of prostate and rectum for plans with different
      margins using an equivalent uniform dose (EUD) based biological model. The 50%
      tumor control dose (TCD50) of 60Gy for prostate and the median toxic dose (TD50)
      of 55Gy for rectum were used in the calculation. RESULTS: The minimum dose of the
      prostate and the mean dose of the rectum dropped with the decrease of the
      treatment margin. When the posterior treatment margin was reduced from 5mm to
      zero, the EUD of prostate decreased from 83Gy (+/-0.5Gy) to 81Gy (+/-0.5Gy) and
      the TCP dropped from 93.2% (+/-0.1%) to 91.7% (+/-0.1%), the EUD of the rectum
      decreased more significantly from 48.9Gy (+/-0.4Gy) to 32.5Gy (+/-0.5Gy) and the
      NTCP dropped from 13.3% (+/-1.5%) to 0.03% (+/- 0.01%). CONCLUSIONS: The
      treatment margin size affects the dose to the target and the nearby critical
      structure. More significant impact on NTCP has been observed than on TCP. This
      gives us some room to consider the quality of the patient's after-treatment life.
      A wise choice of treatment margin can be made based on physician's opinion and
      patient's preference on the tumor control and the quality of life.

PMID- 28517483
TI  - SU-E-T-475: Nano-Dosimetric Track Structure Scoring including Biological Modeling
      with TOPAS-NBio.
AB  - PURPOSE: To develop a nano-dosimetric Monte Carlo simulation package, TOPAS-nBio,
      based on the TOPAS (TOol for PArticle Simulations) framework that is being
      developed in a collaboration between the Massachusetts General Hospital (MGH),
      the SLAC National Accelerator Laboratory and the University of California, San
      Francisco. The goal is to incorporate biological processes on a sub-cell level
      that will provide the basis for a wide range of research in the field of
      radiobiology, such as bystander effects, biological dose calculations and effects
      of nano-particles on radiation therapy. METHODS: The TOPAS framework has been
      utilized to extend the functionality of this tool for particle transport to
      include nano- dosimetry. The physics lists of TOPAS have been extended to include
      efforts by the Geant4-DNA group to model physics on nanometer scales, including
      chemical processes of the first millisecond after irradiation. TOPAS-nBio uses
      the functionality of TOPAS to score energy depositions on nanometer scales. A
      simulation of the setup of a cell culture irradiation experiment has been used as
      to test the feasibility of the project. RESULTS: Track structures for an
      irradiation of a cell culture experiment were successfully obtained. Delta
      electron distributions have been produced and single track delta electrons and
      their energy depositions were observed. CONCLUSIONS: This study is a first step
      in the development of TOPAS-nBio, a tool that aims at bringing nanometer scale
      radiation physics and biology together and make Monte Carlo simulations
      accessible for all radiobiology researchers. The results presented here show a
      first proof of concept for the development of TOPAS-nBio.

PMID- 28517484
TI  - SU-E-T-446: Effect of Dose Calculation Grid Size Variability on the Specification
      of Spinal Cord Dose Tolerance for Spinal Stereotactic Body Radiation Therapy.
AB  - PURPOSE: To investigate the effect of the dose grid resolution variability on the
      spinal cord dose for spinal SBRT treatments. METHOD: 10 CyberKnife plans were
      selected for the proximity of the PTV to the spinal cord. All dose distributions
      were calculated with Monte Carlo using high spatial resolution and minimal
      relative uncertainty. The plans were renormalized to a 16 Gy prescription dose
      and to ensure a target coverage > 95% in order to compare the calculated dose
      distributions. Each dose matrix was resampled 12 times, covering a grid
      resolution range of 0.95 mm to 13.52 mm. The spinal cord DVHs were generated for
      each resampled dose grid. The variations of the maximum point dose (DmaxCord) and
      dose-coverage to partial volumes (D[V]) up to 5 cc were investigated against the
      grid resolution. RESULTS: The mean variation of DmaxCord with grid resolution is
      characterized by an inverse power law, with a sharp initial decrease leading to
      potentially large underestimates of DmaxCord (24%, 40% and 55% at resolutions of
      2 mm, 4 mm and 8 mm). The variability of mean D[V] values decreases from smaller
      to larger grid resolutions, however large disparities are observed between
      patient plans. We introduced the variability threshold volume (Vth) as a
      constraint to express the dose coverage independently from the grid resolution.
      For resolutions up to 8 mm, the mean Vth value is (0.96+/-0.10) cc with a
      corresponding dose coverage of (26+/- 12) % relative to the initial DmaxCord
      value. CONCLUSIONS: Dose distributions calculated with grid resolutions larger
      than 2 mm could Result in significant underestimates of DmaxCord. Furthermore,
      the sensitivity of the dose coverage to grid resolution variability is patient
      dependent. Consequently, a specified cord dose tolerance should be quoted at a
      particular grid resolution uniformly adopted between institutions; 2 mm or less
      is an appropriate value.

PMID- 28517485
TI  - SU-E-T-486: Volume and Location Dependence on the Difference Between Monte Carlo
      and Pencil Beam Dose Calculations for Lung Stereotactic Body Radiation Therapy.
AB  - PURPOSE: Stereotactic body radiotherapy has been an efficacious treatment
      modality for early stage non-small cell lung cancer. The accuracy of dose
      calculations is in question due to the presence of inhomogeneity. It was required
      in several clinical trials to calculate dose without heterogeneity correction.
      However, to better correlate the outcomes with the planned dose, accurate dose
      calculation with heterogeneity correction is highly desirable. METHODS: We
      compared the recalculated dose with Monte Carlo (MC) algorithm to the original
      Pencil Beam (PB) calculations for clinical lung SBRT plans. Thirty-one clinical
      plans that followed protocol guidelines were retrospectively investigated.
      Dosimetric parameters D1, D95 and D99 for the PTV and D1 for organs at risk were
      compared. Correlations of mean lung dose and V20 of lungs between two
      calculations were investigated. RESULTS: Compared to the PB calculations without
      heterogeneity correction in clinical plans, we found that in terms of D95 of PTV,
      (1) the two calculations resulted in similar D95 for edge tumors with volumes
      greater than 25.1cc; (2) an average overestimation of 5% in PB calculations for
      edge tumors with volumes less than 25.1cc; and (3) an average overestimation of
      9% or underestimation of 3% in PB calculations for island tumors with volumes
      smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the
      PB calculation resulted in an average reduction of 23.8% and 15.3% in D95 for
      island and edge lesions respectively compared to the MC calculation. For organs
      at risks, no clinical meaningful differences were found among all the
      comparisons. Excellent correlations for mean dose and V20 of lungs were observed
      between the two calculations. CONCLUSIONS: Using a single scaling factor to
      account for the differences in using heterogeneity correction may not be
      sufficient. To understand dose-response relation in Lung SBRT, accurate dose
      calculation such as the Monte Carlo algorithms is highly recommended.

PMID- 28517486
TI  - SU-E-T-457: Multi-Mode Model - A Consistent Approach for Conventionally
      Fractionated Radiotherapy and Stereotactic Body Radiotherapy.
AB  - PURPOSE: The accuracy of dosimetric analysis and outcome comparison between
      conventionally fractionated radiation therapy(CFRT) and stereotactic body
      radiotherapy(SBRT) requires reliable radiobiological modeling. The aim of this
      work was to further improve the multi-mode model(MMM) for both CFRT and SBRT.
      METHODS: MMM assumes the existence of different modes of cell killing as a Result
      of radiation damage to different parts of a cell, e.g., a single severe damage to
      the DNA or two or more small damages to the membrane or DNA. The cell survival
      probability can then be calculated by s=Product_(i=1,n){1-(1-e(-d/Di))(i)}, where
      i represents the i-th mode of cell killing that requires i potentially
      unrepairable damages to the cell as a result of radiation dose d and Di is the
      dose that gives 63% probability to cause an unrepairable damage for the i-th
      mode. The dose rate effect is included in MMM assuming 1/D_i=(k_i- r_i/U), where
      k_i is the radiation damage rate, r_i the repair rate and U the dose rate. The
      low-dose hypersensitivity is also included in the new model. RESULTS: A
      comparison of the goodness-of-fit of the LQ, multitarget, USC and MMM to the
      survival curve of the H460 non-small-cell lung cancer cell line showed the same
      agreement between USC and MMM with the survival data, which was significantly
      better than the fits to the LQ and multitarget models. The parameters used for
      the LQ, multitarget and USC models were alpha=0.33Gy, alpha/beta=10Gy, D_T
      =6.2Gy, D_0 =1.25Gy and D_q =1.8Gy. The parameters for MMM(n=4) were D_1=4.0Gy,
      D_2=4.01Gy, D_3=3.08Gy and D_4=41Gy. CONCLUSIONS: MMM offers a superior
      description of the mammalian cell survival curve in both conventional and
      ablative dose ranges, which can be used for designing new fractionation schemes
      and predicting and understanding treatment outcomes for both CFRT and SBRT.

PMID- 28517487
TI  - SU-E-T-497: Study of Restricted Mass Stopping Power Ratio in Small Electron Tube
      Fields.
AB  - PURPOSE: Electron tubes with small radii are useful to treat narrow regions which
      cannot accommodate normal electron applicators. In small electron fields, it is
      not trivial to estimate restricted mass stopping power ratio (MSR), which is
      needed to evaluate dose from ion chamber measurement. We studied MSRs in small
      electron tube fields using the Monte Carlo simulation. METHODS: Electron tubes
      with radii, 3 and 2.5 cm, were used in this study. Nominal electron energies were
      6 and 9 MeV. There were two types of tubes. One has a normal cut but the other
      has a 45-degree cut. For the normal cut tube, percent depth dose (PDD) in water
      was evaluated along the center of axis (CAX) of a beam. For the 45-degree cut
      tube, PDD was evaluated along the vertical line from the intersection of the CAX
      and the phantom surface with 45-degree gantry angle. The MSRs and mean electron
      energies were calculated using the Monte Carlo simulation. RESULTS: We found good
      agreement between the measured and calculated PDDs. The changes of mean energies
      from those in the 10*10 cm2 field at the depth of maximum dose (dmax) were very
      small for the normal cut electron tubes. For the 45-degree cut tubes, the changes
      of mean energies at dmax were less than 1 MeV. The MSRs in the normal cut tube
      fields were almost the same as those in the 10*10 cm2 field at the corresponding
      depths. The MSRs for the 45-degree cut tubes deviated from those in the 10*10 cm2
      by about 1% (1.5 % at most). CONCLUSIONS: We evaluated the mean energies and MSRs
      in small electron tube fields. The deviations of them from the values in the
      10*10 cm2 were small. The maximum difference of MSR was 1.5% in 45-degree cut
      tube fields. This work was supported by KAKENHI (23791449), Japan Society for the
      Promotion of Science, and Cancer Professional Training Plan, The Ministry of
      Education, Culture, Sports, Science and Technology, Japan.

PMID- 28517488
TI  - SU-E-T-468: Gamma Knife Perfexion Dosimetry: A Monte Carlo Model of One Sector.
AB  - PURPOSE: We have implemented a Monte Carlo (MC) based dose computation model of
      one sector of the Gamma Knife Perfexion (GK PFX) using the Penelope MC dosimetry
      codes. The single sector simulation was rotated about the z-axis to model all
      eight GK sectors. GK dosimetric aspects examined include: 1) output factors (OF)
      for each of the three GK collimator sizes (4, 8, 16 mm), 2) OFs for each source
      row and collimator size, and 3) dose distribution profiles along the x- and z
      axes, compared to film measurements and dose calculations from the Leksell
      GammaPlan (LGP) workstation. METHODS: We defined the internal GK PFX geometry in
      Penelope with the aid of vendor-supplied proprietary information. A single source
      per row was modeled for five rows for each of the 3 collimators (15 beams
      modeled). MC simulations were carried out on a Linux cluster. Phase space files
      (PSFs) were collected for the 15 modeled collimators then rotated about the z
      axis to model the sector of 24 sources per collimator. 3D dose distributions from
      the MC model, film, and LGP DICOM-RT dose exports were analyzed using Matlab. For
      OF calculations, a 16 cm diameter dosimetry sphere was modeled with a virtual
      detector volume at its center. RESULTS: Good agreement is found for row- and
      total-output factors (greatest deviation of any type < 4%) compared to reference
      values. Off-axis factors closely follow LGP predicted dose distributions along
      the x-axis and differ on the inferior side of the z-axis. CONCLUSIONS: Detailed
      geometric representations (radiation source, device components) of the GK PFX are
      required for high fidelity MC simulations. Calculated GK PFX OF values depend on
      the simulated detector volume size (4 mm OF most dependent). Our model shows
      strong agreement for the GK PFX OFs and dose profile curves compared to reference
      values. Non-disclosure agreement for proprietary information with Elekta AB. No
      financial contribution.

PMID- 28517489
TI  - SU-E-T-479: Skin Dose from Flattening Filter Free Beams: A Monte Carlo
      Investigation.
AB  - PURPOSE: Flattening filter free (FFF) beams in radiotherapy have advantages such
      as shorter treatment delivery time and lower out-of-field dose compared with
      conventional flattened beams. This study investigates in detail the skin dose
      induced by FFF beams from a TrueBeam accelerator (Varian Medical Systems, Palo
      Alto, CA) using Monte Carlo method. METHODS: Phase space files generated using
      real geometry of a TrueBeam accelerator above the jaws, were used as the input
      radiation source files in beam simulation for various field sizes using BEAMnrc.
      Phase space files for various field sizes were generated at the phantom surface.
      DOSXYZnrc was used for dose calculations in phantom and in patient using the
      generated phase space files as source input files. RESULTS: The calculated
      percentage depth dose curves and profiles in water agreed with measurements
      within +/- 2% for the high dose region and +/-2 mm in the penumbra. The peak
      fluence of a 6 MV FFF beam with the same electron beam incident on the target is
      about 3 times that of a flattened beam . The mean energy of a 6 MV FFF beam is
      0.92-0.95 MeV while it is 1.18-1.30 MeV for the flattened beam. Due to the mean
      energy difference, the dose in a 6 MV FFF beam is about 6% (of the maximum dose,
      or 12% of local dose) higher at depth of 1 mm compared with a flattened beam.
      CONCLUSIONS: Due to the lower mean photon energy, in an FFF beam the surface
      (skin) dose is slightly higher compared to the conventional flattened beam of the
      same field size.

PMID- 28517490
TI  - SU-E-T-450: An Evaluation Study of Dose Calculation Algorithms for Stereotactic
      Body Radiation Therapy in Heterogeneous Phantom.
AB  - PURPOSE: In Stereotactic body radiation therapy (SBRT) higher dose per fraction
      is delivered to patients and thus the need for an accurate dose computation is
      further elevated. However under such conditions of small field geometries, the
      electronic equilibrium can be lost, making it challenging for the dose
      calculation algorithm to accurately predict the dose, especially in the presence
      of tissue heterogeneities. Thus the aim of this study is to evaluate the
      performance of the algorithms implemented in our treatment planning system.
      METHODS: In this study different phantoms were designed to model the lung with a
      small tumor volume of sizes that are usually encountered in SBRT. Solid water and
      cork slabs were used in constructing the phantom body. Perspex pieces of
      different diameters were created to be inserted in precut holes in the cork to
      simulate the tumor. The various dose calculation algorithms that are implemented
      in our CMS XIO planning system were then used for dose calculation inside the
      target. RESULTS: A significant discrepancies between maximum, minimum and mean
      dose for PTV was found between Clarkson, FFT Convolution, Fast superposition and
      superposition algorithms in dose calculation for the lung tumor. The FFT
      Convolution and Clarkson algorithms have higher calculated minimum dose than that
      predicted by the superposition and the fast superposition algorithm. A percentage
      difference as high as 62.5% was obtained between Clarkson and the superposition
      algorithm in the estimated minimum dose. A percentage difference up to 13.4% was
      obtained between the FFT Convolution and the superposition algorithm for the
      estimated maximum dose. Superposition and fast superposition showed little
      discrepancies for maximum, minimum and mean dose for the PTV. CONCLUSION: It is
      very critical to address the accuracy of dose computation for SBRT as a
      significant dose overestimation can occur inside the target due to the
      heterogeneous geometries.

PMID- 28517491
TI  - SU-E-T-490: Comparison of XVMC Monte Carlo Dose Calculations with Eclipse AAA
      Calculations for RapidArc Plans.
AB  - PURPOSE: The consistency between the AAA and XVMC algorithm in the treatment
      planning for RapidArc is investigated. While the majority of the radiation field
      is blocked by the MLC system, multiple small dose islands with MLC opened only
      slightly can be observed in one control point. This raises questions on how
      accurate the clinically used AAA algorithm in Eclipse is able to calculate
      RapidArc dose distributions. The fast Monte Carlo Code XVMC was used as a
      benchmark to test the AAA algorithm. METHODS: RadpidArc plans of 25 patients were
      calculated with AAA and XVMC. The patient cohort consisted of 4 different cancer
      sites (H&N, upper abdominal, lung, prostate). Dose distributions, PTV and OAR
      coverage were compared looking at the PTV mean dose Dmean, the volume V95% of the
      PTV receiving 95% of the prescribed dose, the dose D95% delivered to 95% of the
      PTV Volume, the percentage PTV mean dose with respect to the prescribed dose
      Dmean/prescr and OAR mean dose. RESULTS: The recalculation of RapidArc plans
      yielded good agreement of both calculation algorithms for treatment plans of all
      four cancer sites. PTV mean dose differences of AAA and XVMC were found to be in
      between -0.11% and 4.89% of the prescribed dose. The mean dose difference found
      was 0.48+/-0.77 Gy. Local dose differences were found when comparing dose
      distributions in regions of big mass density differences and in high dose
      regions. One head and neck plan and one prostate plan revealed significant
      differences in PTV coverage (DeltaDmean=3.25 Gy) and OAR mean dose (prostate mean
      dose -13.71 Gy) respectively. CONCLUSIONS: The vast majority of treatment plans
      calculated with the AAA algorithm were found to agree within the expected and
      acceptable tolerances compared to XVMC results. Nevertheless in some cases dose
      differences were observed that could be of clinical significance. This work was
      funded by a Varian grant. Wolfram Laub is working in the physics group of CMS.

PMID- 28517493
TI  - Accuracy of computed tomography for detecting hepatic steatosis in donors for
      liver transplantation: A meta-analysis.
AB  - BACKGROUND: The accuracy of computed tomography (CT) for detecting donor hepatic
      steatosis (HS) before liver transplantation is not well established. METHODS: A
      meta-analysis was performed to determine the accuracy of CT for HS detection in
      liver donor candidates. Pooled sensitivity, specificity, positive and negative
      likelihood ratios, hierarchical summary receiver operating characteristic (HSROC)
      curves, and the area under the curve (AUC) were estimated using HSROC and
      bivariate random-effects models. RESULTS: Twelve studies involving 1782 subjects
      were eligible for this meta-analysis. For detecting significant HS (>10%-30%
      steatosis in liver pathology) with CT in liver donors, the pooled sensitivity,
      specificity, positive likelihood ratio, and negative likelihood ratio were 0.81
      (95% confidence interval [CI]: 0.70-0.89), 0.94 (95% CI: 0.90-0.96), 13.7 (95%
      CI: 8.1-23.1), and 0.20 (95% CI: 0.12-0.33). The AUC was 0.95 (95% CI: 0.92
      0.96). For detecting the presence of HS, these corresponding diagnostic estimates
      were 0.50 (95% CI: 0.36-0.64), 0.90 (95% CI: 0.83-0.95), 5.2 (95% CI: 3.1-8.9),
      0.55 (95% CI: 0.42-0.72), and 0.80 (95% CI: 0.76-0.83). Moderate-to-high
      heterogeneity was detected. CONCLUSION: Computed tomography shows high accuracy
      in detecting significant HS while poor accuracy in detecting the presence of HS
      in liver donors. Donors estimated to have significant HS by CT may avoid
      unnecessary liver biopsy.

PMID- 28517494
TI  - SU-F-BRCD-02: Activity Assay of a Y-90 Microsphere Sample Using a Coincidence
      Detection System.
AB  - PURPOSE: This work takes advantage of a newly-determined, low-uncertainty
      branching ratio of the internal pair production component of Y-90 decay to
      spectroscopically assay the activity of a Y-90 microsphere sample with a
      coincidence detection system (CDS). METHODS: The CDS pairs a HPGe detector with a
      large NaI detector. The system is able to electronically filter the
      bremsstrahlung continuum from the photon spectrum by gating the energy signal
      from the HPGe with the coincidence signal. This reduces the uncertainty in the
      spectra measurement compared to measurements with a single HPGe detector. A
      series of pulsers were used to correct for counting losses. A geometric
      characterization was completed to find the optimal source position for
      measurements. An efficiency calibration of the CDS was completed using a Na-22
      standard source. To validate the measurement accuracy of the CDS, the activity of
      a Y-90 standard activity solution from the NIST SRM program was determined and
      compared to the value given by NIST. The CDS was then used to determine the
      activity of a Y-90 microsphere sample. This value was compared to the 3.0 GBq
      value given by the manufacturer. RESULTS: The activity determined with the CDS
      was within 2.6% from the given activity of the NIST SRM source, which is within
      the expanded uncertainty associated with the CDS measurement. The activity of the
      Y-90 microsphere sample was determined to be 3.72 GBq +/- 1.9%. This is 19%
      higher than the manufacturer-stated activity of 3 GBq. This is outside the
      manufacturer-stated uncertainty of +/-10%. CONCLUSIONS: The ability of CDS to
      determine the activity of a Y-90 source has been validated with comparison to a
      NIST Y-90 standard activity solution. The use of the CDS has been extended to
      determine the activity of a Y-90 microsphere sample.

PMID- 28517495
TI  - SU-E-T-621: Comprehensive Study of Head and Neck IMRT Parameters on Planning and
      Delivery Efficiency, Plan Quality, and Dose Accuracy.
AB  - PURPOSE: To optimize planning and delivery efficiency, and quality of head and
      neck IMRT through the evaluation of planning parameters. This study also serves
      to identify the impact on dose accuracy due to calculation grid size. METHODS:
      Eleven head and neck patients, 45 trials per patient (495 trials in total), were
      evaluated varying IMRT parameters of dose grid, minimum MU per segment, minimum
      segment area, and control point number. Plans were recomputed on Pinnacle
      Treatment Planning System (TPS), and scaled to the planning target volume (PTV)
      constraint of 95% volume. Differential dose volume histograms (DVHs) were
      exported, and a program was written to compile DVH results. Plans were delivered
      on an Elekta Synergy linear accelerator to assess delivery time. Plan quality,
      calculation time, and delivery time served as this study's endpoints. RESULTS:
      The 4 mm dose grid with 2 mm fluence grid in each direction, saving 1/3 the
      computation time, were most comparable by DVH results to the 2 mm dose and
      fluence grid. Dose uncertainty due to dose calculation grid effect was as high as
      8.2%, 5.5 Gy for PTVs and 13.3%, 2.1 Gy for organs at risk. Smaller volumes and
      high gradient regions were more susceptible to uncertainties. Threshold values
      that maintained adequate plan quality were 5 cm2 for minimum segment area and 5
      MU for minimum MU. Minimum MU was more costly in terms of plan quality compared
      to the minimum segment area. CONCLUSIONS: DVH differences can be effectively used
      to quantify the dose grid calculation uncertainty. For minimum MU and segment
      area, the DVH differences are an effect of the intensity map, defined by MLC
      shape and the number of control points. Exceeding the adequate number of control
      points diminishes returns of plan quality and increases patient treatment time.

PMID- 28517492
TI  - Practical considerations of linear accelerator-based frameless extracranial
      radiosurgery for treatment of occipital neuralgia for nonsurgical candidates.
AB  - Occipital neuralgia generally responds to medical or invasive procedures.
      Repeated invasive procedures generate increasing complications and are often
      contraindicated. Stereotactic radiosurgery (SRS) has not been reported as a
      treatment option largely due to the extracranial nature of the target as opposed
      to the similar, more established trigeminal neuralgia. A dedicated phantom study
      was conducted to determine the optimum imaging studies, fusion matrices, and
      treatment planning parameters to target the C2 dorsal root ganglion which forms
      the occipital nerve. The conditions created from the phantom were applied to a
      patient with medically and surgically refractory occipital neuralgia. A dose of
      80 Gy in one fraction was prescribed to the C2 occipital dorsal root ganglion.
      The phantom study resulted in a treatment achieved with an average translational
      magnitude of correction of 1.35 mm with an acceptable tolerance of 0.5 mm and an
      average rotational magnitude of correction of 0.4 degrees  with an acceptable
      tolerance of 1.0 degrees . For the patient, the spinal cord was 12.0 mm at its
      closest distance to the isocenter and received a maximum dose of 3.36 Gy, a dose
      to 0.35 cc of 1.84 Gy, and a dose to 1.2 cc of 0.79 Gy. The brain maximum dose
      was 2.20 Gy. Treatment time was 59 min for 18, 323 MUs. Imaging was performed
      prior to each arc delivery resulting in 21 imaging sessions. The average
      deviation magnitude requiring a positional or rotational correction was 0.96 +/-
      0.25 mm, 0.8 +/- 0.41 degrees , whereas the average deviation magnitude deemed
      within tolerance was 0.41 +/- 0.12 mm, 0.57 +/- 0.28 degrees . Dedicated quality
      assurance of the treatment planning and delivery is necessary for safe and
      accurate SRS to the cervical spine dorsal root ganglion. With additional
      prospective study, linear accelerator-based frameless radiosurgery can provide an
      accurate, noninvasive alternative for treating occipital neuralgia where an
      invasive procedure is contraindicated.

PMID- 28517496
TI  - MO-A-217BCD-02: Yttrium-90 Microsphere Therapy Planning and Dose Calculations.
AB  - : Yttrium-90 microsphere therapy, a form of radiation therapy, is an increasingly
      popular option for care of patients with liver metastases or unresectable
      hepatocellular carcinoma. The therapy directly delivers Yttrium-90 microspheres
      via the hepatic artery to specifically targeted disease sites. Following Yttrium
      90 microsphere therapy, a vast majority of Yttrium-90 microspheres preferentially
      lodge in neoplastic tissue due to their embolic size (mean diameter 32 &#956;m)
      and targeted trans-arterial delivery. Once embolized the microspheres do not
      migrate but deposits up to 90% of its energy in the first 5 mm of tissue. Prior
      to Yttrium-90 microsphere therapy, a 99mTc-MAA examination is conducted to
      evaluate catheter placement and lung-shunt fraction. The lung shunt fraction and
      absorbed dose estimates for lung and liver that guide Yttrium-90 administered
      activity are based on nuclear medicine imaging. A review of the pre- and post
      therapy imaging procedures underlying Yttrium-90 microsphere therapy will be
      presented. Calculation of the lung shunt fraction and dosimetry models to
      estimate radiation absorbed doses will be discussed. Radiation safety issues will
      be also be reviewed. LEARNING OBJECTIVES: 1. To understand the imaging sequence
      for Yttrium-90 microsphere therapy planning and dose calculations 2. To
      understand calculation of lung shunt fraction and estimation of absorbed dose for
      lung and liver 3. To become familiar with radiation safety and regulations
      surrounding Yttrium-90 microsphere therapy.

PMID- 28517497
TI  - SU-E-T-633: To Evaluate Dosemetric Differences of IMRT Lung Plans Generated from
      RayStation Multi-Criteria Optimization (MCO) and Pinnacle Direct Machine
      Parameters Optimization (DMPO).
AB  - PURPOSE: To evaluate dosimetric differences of IMRT lung plans generated from
      RayStation* Multi-Criteria Optimization (MCO) and Pinnacle Direct Machine
      Parameters Optimization (DMPO) Methods: Five patients previously treated with
      plans from Pinnacle v9.0 using DMPO algorithm were re-planned on RayStation
      v2.4.8.180 using MCO Pareto plans with same dose constraints, beam angles and
      objectives. The prescription was 60 Gy to 95% of PTV. Planning outcomes such as
      D95 (95% of volume receiving the prescribed dose), D2, D1 for PTV, D33 and mean
      dose for heart, V20 (volume receives at least 20 Gy) and mean dose for lung, max
      dose for cord were reported for evaluation according to our clinical protocols.
      The conformity of the prescription isodose volume to PTV was evaluated as
      conformity index (CI). Planning time was also observed. RESULTS: The mean volume
      of PTV was 356 +/- 141 cm3 . The D95 of PTV with RayStation was improved and more
      uniform compared to plans from Pinnacle (59.4 +/- 0.2 vs. 59.2 +/- 0.8 Gy),
      respectively. D2 and D1 of PTV were lower with RayStation plans. Mean dose and
      V20 of total lung were lower for all RayStation plans with max dose of cord, and
      D33 and mean dose of heart following the same trend. CI was better with
      RayStation compared to Pinnacle (1.09 +/- 0.06 vs. 1.16 +/- 0.11). Planning time
      was faster with RayStation from Pinnacle (few minutes. vs. minimum of 20 minutes,
      approximately). CONCLUSIONS: MCO planning automatically generates a set of Pareto
      optimized solutions for given objectives to allow tradeoffs between targets and
      critical organs. RayStation can achieve better uniform tumor coverage with fewer
      hot spots while sparing more critical structures. MCO Pareto based IMRT plans is
      helpful in determining the best optimized dosimetry with shorter planning time.

PMID- 28517498
TI  - MO-A-213AB-10: Scattering System Optimization for Proton Therapy.
AB  - PURPOSE: To describe a method for optimization and production of a dual
      scattering system for proton beam delivery. METHODS: Dual-foil passive scattering
      is currently the prevalent modality for proton therapy delivery. Large uniform
      proton fields are created using a 2-stage scattering system comprising an
      upstream uniform lead foil (stage 1) followed by a contoured lead/Lexan foil to
      provide beam and range uniformity (stage 2). Optimizing the parameters of these
      foils, including thickness, contour and placement, provides not only a flat and
      symmetrical radiation field with a uniform range, but also affects the overall
      efficiency of the beam line. An analytical method for optimizing the scattering
      system design was applied and validated with GEANT4 simulations. This method has
      been used to create passively scattered therapeutic and research proton fields at
      our proton therapy facility. A novel Cerrobend casting method is described that
      allows for cost-effective and accurate production of this important beam-line
      component. RESULTS: A number of dual scattering foil combinations for research
      and therapeutic purposes have been created and were evaluated with GEANT4
      simulations. We demonstrated that the use of this system can generate passively
      scattered proton fields up to 60cm diameter with improved efficiency and beam
      flatness over existing dual-scattering systems. Scattering system performance was
      verified using physical measurements including Gafchromic film and ion chamber
      data. CONCLUSIONS: This analytical method allows the user to optimize the proton
      dual scattering system with respect to specific input parameters, while the
      casting method provides a cost-effective way to create a unique scattering system
      for a given application.

PMID- 28517499
TI  - SU-E-T-644: Incorporating High Dose Inhomogeneity into SBRT Treatment Planning.
AB  - PURPOSE: By encouraging greater dose inhomogeneity in the PTV, SBRT allows higher
      doses to be delivered to the target, and thus improves local control and
      treatment outcome. This work aims to incorporate the high dose inhomogeneity
      constraint into SBRT treatment planning in safer manner. METHODS: Two approaches
      are proposed to achieve high dose inhomogeneity: (1) implicitly reduce dose
      uniformity by increasing the error tolerance for the PTV; (2) explicitly add
      specific localized information by introducing the structure, located at 5 mm to 1
      cm inside the PTV, and prescribe a higher dose. We formulate the inverse planning
      problem in a total-variation minimization framework to reduce the complexity of
      the fluence maps. The optimization problem was solved with a fast and efficient
      first-order method called TFOCS. For validation, 15-beam IMRT plans were
      generated for a lung SBRT case, where normal tissue constrains are directly taken
      from the RTOG lung SBRT protocol 0915. The inhomogeneous plans generated from the
      two approaches were compared with a homogeneous plan in terms of dose
      distributions. RESULTS: Both inhomogenous plans delivered higher doses to the
      target compared with the homogenous plan, with a ~10% increase in max dose. The
      implicit approach increased the high dose spillage (outside PTV) to 0.52%,
      leading to more tissue damage. On the other hand, the explicit approach
      maintained the high dose spillage at a lower level of 0.18%, similar to that of
      the homogenous plan. Moreover, with local information of the PTV, the explicit
      approach allocated the hot spots around the center of the PTV, ensuring the
      safety and effectiveness of SBRT. CONCLUSIONS: The proposed method using specific
      localized information inside the PTV can safely and effectively deliver high
      doses to the target and lead to improved local control.

PMID- 28517501
TI  - SU-E-T-625: Robustness Evaluation and Robust Optimization of IMPT Plans Based on
      Per-Voxel Standard Deviation of Dose Distributions.
AB  - PURPOSE: Proton dose distributions, IMPT in particular, are highly sensitive to
      setup and range uncertainties. We report a novel method, based on per-voxel
      standard deviation (SD) of dose distributions, to evaluate the robustness of
      proton plans and to robustly optimize IMPT plans to render them less sensitive to
      uncertainties. METHODS: For each optimization iteration, nine dose distributions
      are computed - the nominal one, and one each for +/- setup uncertainties along x,
      y and z axes and for +/- range uncertainty. SD of dose in each voxel is used to
      create SD-volume histogram (SVH) for each structure. SVH may be considered a
      quantitative representation of the robustness of the dose distribution. For
      optimization, the desired robustness may be specified in terms of an SD-volume
      (SV) constraint on the CTV and incorporated as a term in the objective function.
      Results of optimization with and without this constraint were compared in terms
      of plan optimality and robustness using the so called'worst case' dose
      distributions; which are obtained by assigning the lowest among the nine doses to
      each voxel in the clinical target volume (CTV) and the highest to normal tissue
      voxels outside the CTV. The SVH curve and the area under it for each structure
      were used as quantitative measures of robustness. Penalty parameter of SV
      constraint may be varied to control the tradeoff between robustness and plan
      optimality. We applied these methods to one case each of H&N and lung. RESULTS:
      In both cases, we found that imposing SV constraint improved plan robustness but
      at the cost of normal tissue sparing. CONCLUSIONS: SVH-based optimization and
      evaluation is an effective tool for robustness evaluation and robust optimization
      of IMPT plans. Studies need to be conducted to test the methods for larger
      cohorts of patients and for other sites. This research is supported by National
      Cancer Institute (NCI) grant P01CA021239, the University Cancer Foundation via
      the Institutional Research Grant program at the University of Texas MD Anderson
      Cancer Center, and MD Andersona?TMs cancer center support grant CA016672.

PMID- 28517500
TI  - SU-F-BRCD-06: Multiple Anatomy Optimization of Accumulated Dose.
AB  - PURPOSE: Multiple anatomy optimization (MAO) utilizing deformable dose
      accumulation on entire 4DCT data sets is implemented to overcome ambiguity
      between optimal dose defined on a single anatomy and optimal accumulated dose
      resulting from dose delivery to moving and deforming anatomy. METHODS: Six lung
      cancer patients are planned using two methods of radiotherapy optimization: the
      internal target volume (ITV) envelope method and MAO, which simultaneously
      optimizes a single fluence for delivery to all 10 breathing phases such that the
      accumulated dose satisfies the plan objectives. Target dose is constrained to 70
      Gy. The ITV-plan is optimized on a single breathing phase with the planning
      target volume defined as the ITV; the MAO target is the moving CTV. MAO is
      compared to single image ITV optimization based on the accumulated dose assuming
      equal monitor-units to each phase. Dose-volume differences between single image
      estimations and 10-image accumulation are examined. RESULTS: Single image optimal
      dose distributions overestimate target V70 by 4.2%+/-3.1% (average, one standard
      deviation) and in five of six cases ipsilateral lung V20 is underestimated
      (1.4%+/-0.9%). For these five cases, MAO increases V70 by 2.8%+/-2.5% (maximum of
      6% increase in V70) and reduces ipsilateral lung V20 by up to 3% (average
      decrease of 1.2%+/-1.3%). Contralateral lung V20, esophagus V25, and heart V30
      are also reduced by up to 5%, 3%, and 3%. For the sixth case, lung tumor motion
      is on the order of the dose voxel size (3mm), and MAO did not improve upon the
      ITV plan. CONCLUSIONS: Dose-volume optimization on a stationary image does not
      ensure accumulated dose coverage to the moving CTV. Multiple anatomy optimization
      can remove dose ambiguity and improve plan quality. P01CA11602 and Philips
      Medical Systems.

PMID- 28517502
TI  - MO-A-213AB-03: Commissioning of a Clinical Chair for Patients Treated in the
      Seated Position Using an Inclined Beam Line Treatment Room.
AB  - PURPOSES: A chair, coupled to a robotic patient positioning system (PPS) was
      manufactured to treat an intracranial tumor in a proton incline beam-line system.
      Treating patients in the seated position as accurately and efficiently as a
      treatment table requires the essential functions of isocentric rotation and a
      weight-sagging-correction algorithm for positioning patients in the seated
      position. METHODS AND MATERIALS: The chair design incorporated a down-slope arm
      to achieve the desired beam-line height. To overcome this limitation of only 125
      degree rotation on PPS, five indexed positions of the seat-base-plate (SBP) were
      implemented. An in-house developed optical tracking system using a six degree-of
      freedom optical camera system was used to align the treatment room coordinate
      system with the chair coordinate system at all SBP positions. Furthermore, this
      optical tracking system quantified the sagging effect due to both the height and
      weight of a variety of patients. RESULTS: The optical tracking system can measure
      accuracy of 0.1 degree and 0.1 mm. The SBP rotating axis was aligned within 0.1
      degree to PPS rotating axis. A residual precession of chair rotation was found to
      be an ellipse with long axis of 2.0 mm and short axis of 1.0 mm. An additional
      0.75 mm deviation occurred between rotating of SBP and PPS axes. Sagging tilt of
      0.6 degree was found on the SBP for the home position for every additional 162
      lbs load. This resulted in a 1.1cm shift (0.65 cm forward and 0.87 cm) for an
      isocenter 90 cm away from the SBP plate. CONCLUSIONS: Using in-house developed
      optical tracking system, the overall maximum displacement of treatment chair
      system from isocenter is within 3.0 mm with known sagging characteristics. This
      characterization is essential to reduce the total treatment time and limited the
      number of X-rays required for accurate patient alignment in the seated position.

PMID- 28517503
TI  - SU-E-T-637: 4D-VMAT Vs. Gated VMAT in Lung Cancer SBRT.
AB  - PURPOSE: To assess plan quality and treatment efficiency of 4D-VMAT and gated
      VMAT in the treatment of non-small cell lung cancer using SBRT. METHODS:
      Treatment planning software was developed in Matlab to simulate both 4D-VMAT and
      gated-VMAT on patients with stage I lung cancer and at least 1 cm of tumour
      motion. Gated-VMAT delivers radiation to the tumour during only a portion of the
      respiratory cycle and hence requires frequent start and stop motions of the
      gantry. In the 4D-VMAT algorithm, target and organ motion from the entire
      respiratory cycle is incorporated during optimization. Gantry moves continuously
      but delivery of each MLC aperture is synchronized to specific phases of target
      motion. All 4D-CT scan consisted of 10 phases and were acquired with the patients
      breathing freely. The SBRT fractionation scheme was 48 Gy in 4 fractions with at
      least 95% of the PTV receiving 100% of the prescription dose. For gated-VMAT, the
      PTV was derived from the ITV of the relevant respiratory phases plus a 5mm
      margin. In the 4D VMAT algorithm, the GTV was defined on a single phase and the
      PTV created with a 5mm margin. PTVs for the other respiratory phases were
      determined through 4D-image registration and deformation using a bspline
      transformation model. For both treatment deliveries, dose was accumulated on the
      maximum exhale phase and DVHs generated. RESULTS: Findings show gated-VMAT and 4D
      VMAT deliveries resulted in maximum doses to most OARs far below SBRT protocol
      constraints. The 4D-VMAT beam on time is on average 8 min. Gated-VMAT will have
      similar beam on time but treatment time can more than double after accounting for
      25 to 35 beam interruptions per arc. CONCLUSIONS: Gated-VMAT and 4D-VMAT were
      able to produce dosimetrically acceptable lung SBRT plans. The advantage of 4D
      VMAT is the greater efficiency in treatment delivery.

PMID- 28517504
TI  - MO-A-BRB-03: A Clinical Review of the Dosimetric and Temporal Impact of
      Unflattened X- Ray Beams.
AB  - : Since July of 2005, the University of Iowa has been using a conventional linear
      accelerator with the flattening filter removed. This presentation will focus on
      the factors affecting the dosimetric accuracy and total delivery time reduction
      found clinically of radiation therapy with an unfiattened beam, focusing on
      standard fractionation IMRT of the head and neck, as well as gated and hypo
      fractionated liver and lung cancer treatments. The dosimetric accuracy of the
      unfiattened beam depends on the planning system beam model, which will be briefly
      reviewed. The technique used to adjust the beam quality to become equivalent with
      a beam utilizing the flattening filter, as well as the approach to define the
      field size for these beams will be described. Finally, the short-term beam
      stability (< 250 msec) for small MU IMRT and gated delivery will be
      characterized, along with the long-term stability from the last 5-years of
      clinical daily quality assurance records. LEARNING OBJECTIVES: 1. Understand
      technique for matching beam quality of unfiattened and flattened beams. 2.
      Understand definition of field size and beam characteristics during initial 200
      msecs. 3. Review improved dosimetric accuracy and temporal advantages of
      unfiattened beams in clinical use.

PMID- 28517505
TI  - SU-E-T-648: Comparison of VMAT Vs Arc Treatment Plans for Patients Undergoing
      SBRT of Early-Stage Non-Small Cell Lung Cancer (NSCLC).
AB  - PURPOSE: To evaluate the dosimetric implications of using VMAT (Volume Modulated
      Arc Therapy) treatment planning techniques compared to traditional Arc therapy
      methods for patients undergoing SBRT (Stereotactic Body Radiation Therapy) for
      early-stage Non-Small Cell Lung Cancer (NSCLC). METHODS: Ten NSCLC cancer
      patients are planned with both VMAT and Arc techniques. The SBRT treatment plans
      comparison was quantified by several Dose-Volume Histogram (DVH) indicators
      including mean, maximum and minimum doses for GTV, ITV, PTV, OAR (Organs At
      Risk), and V95 (volume receiving at least 95% of the prescribed dose) for PTV.
      RESULTS: On average VMAT plans require for treatment delivery 16.6 +/- 20.2 %
      more monitor units (MU) than the traditional Arc plans. The average PTV minimum,
      maximum and mean doses as a percentage of prescribed dose are 94.5 +/- 3.9 %,
      114.1 +/- 3.3 % and 106.6 +/- 1.6 % for VMAT vs 91.6 +/- 4.4 %, 119.5 +/- 5.3 %
      and 109.5 +/- 2.5 % for the Arc technique. The V95 PTV coverage for VMAT plans
      range from 99.4 % to 100 % with a mean of 99.7 %, compared with a range of 96.8 %
      to 100 % with a mean of 99 % for the Arc plans. The maximum dose received by the
      lungs, spinal cord and chest wall show on average significant increases for Arc
      plans as opposed to VMAT plans (5.7 +/- 6 % increase for lungs, 4.4 +/- 9.2 % for
      cord and 2.4 +/- 6.3 % for chest wall). The average mean doses and minimum doses
      for the OAR are similar for both techniques. CONCLUSIONS: The comparison of VMAT
      vs Arc plans for SBRT of NSCLC patients is subject to many variables, including
      GTV and PTV volume sizes, shape and their proximity relative to the OAR.

PMID- 28517506
TI  - SU-E-T-618: Error Compensated Sparse Optimization for Fast Radiosurgery Treatment
      Planning.
AB  - PURPOSE: Radiosurgical treatment planning requires a good approximation of the
      dose distribution which is typically computed on a high resolution grid. However,
      the resulting optimization problem is large, and leads to substantial runtime. We
      study a sparse grid approach, for which we estimate and compensate for the
      expected deviations from the bounds. METHODS: We buildup an estimate of the
      hotspot error distribution by measuring the maximum dose deviation within a voxel
      for a large number of randomly generated beam configurations. This results in a
      conservative estimation of overdosage as a function of upper bound reduction for
      different grid sizes. We adjust the bounds for voxels inside the target volume
      (PTV) according to our estimation thus maintaining the likelihood of dose
      deviations within acceptable limits. The approach was applied to a prostate case,
      where the volumes of interest are large and close to each other. Our planning
      objective is a prescribed dose of 36.25 Gy to the 87% isodose. We employed
      constrained optimization to optimize the lower PTV bound on 2, 4, and 8mm
      isotropic grids. Results were computed on 1mm grid. RESULTS: The initial coverage
      was 93.7%, 92%, and 91%, and the volume exceeding the upper bound was 0.74%,
      1.71%, and 9% for grid sizes of 2, 4, and 8mm, respectively. Changing the upper
      bound by 0.5% and 2.5% for the 4 and 8 mm grids resulted in only 0.75% and 2.2%
      of the volume exceeding the bound. The coverage did not change. Mean optimization
      times were 141.1, 22.6 and 3.4 minutes using the 2, 4 or 8mm grid, respectively.
      CONCLUSIONS: Experiments show that planning on a sparse grid can achieve
      comparable results with those of a high resolution grid, as long as the bounds
      are carefully balanced. This leads to substantially lower optimization times
      which facilitates interactive planning. This work was supported by the Graduate
      School for Computing in Medicine and Life Sciences funded by Germanya?TMs
      Excellence Initiative [DFG GSC 235/1].

PMID- 28517507
TI  - SU-E-T-630: MCO-Informed VMAT Planning for Prostate Cancer.
AB  - PURPOSE: To develop a VMAT optimization procedure using information from Multi
      Criteria Optimization of IMRT plans and to perform a treatment planning
      comparison for prostate cancer patients. METHODS: IMRT plans using Multi-Criteria
      Optimization (MCO), 6 MV photons, 20 and 7 treatment fields were generated for 10
      prostate patients in the RayStation treatment planning system (Version 2.2.13,
      Raysearch Laboratories, Stockholm, Sweden). The prescription dose was 7560 cGy to
      the prostate PTV and 5796 cGy to the seminal vesicles, using a simultaneous
      integrated boost technique. The resulting DVH parameters of the 20 field IMRT-MCO
      plan were used as initial optimization parameters for VMAT planning. The initial
      VMAT plan for each patient was further optimized by adjusting the optimization
      objectives/constraints. Final plan quality was compared using a homogeneity index
      (HI) and D98 for PTV-prostate, V70 and V75 for anterior rectum and V70 for
      bladder. Moreover, delivery efficiency of VMAT and the 7 field MCO-IMRT plans was
      also evaluated. RESULTS: All plans fulfilled the standard clinical objectives.
      The average HI of the PTV-prostate was 0.11 for VMAT, 0.13 for 20 field IMRT-MCO
      and 0.12 for 7 field IMRT-MCO, respectively. Average D98 values were 7191, 7294
      and 7305 cGy for VMAT, 20 field IMRT-MCO and 7 field IMRT-MCO, respectively. For
      organ-at-risk (OAR), V70 and V75 for anterior rectum and V70 for bladder were
      within 3%. Analysis of delivery efficiency shows the estimated delivery time of
      VMAT is less than 2 minutes, while it is 7 min for 7 field IMRT-MCO. CONCLUSIONS:
      MCO-informed VMAT optimization is a useful way to generate optimal VMAT plans.
      The resulting VMAT plan quality essentially matched the MCO-IMRT plan but with a
      shorter delivery time. Dose homogeneity of VMAT is slight superior compared to
      IMRT-MCO while the cold spots are slightly inferior. Furthermore, there is no
      clinically significant difference in OAR sparing. Funding support provided by NCI
      Federal Share Proton Beam Program Income Grant and Raysearch Laboratories.

PMID- 28517508
TI  - MO-A-213AB-07: Evaluation of Distal Dose Surface with In-Room PET for Proton
      Therapy Monitoring.
AB  - PURPOSE: The objective of this study is to evaluate the feasibility of proton
      beam treatment verification using in-room PET. As of February 2012, four patients
      have been studied in a clinical trial. In addition, we suggest a new method
      comparing the distal surface of the measured and simulated PET activities to
      verify the location of the distal dose surface. METHODS: Patients were scanned
      for 20 minutes with an in-room PET positioned next to the proton treatment head
      in a gantry room for beam delivery using passive scattering. The time between end
      of treatment and the start of the scan was within about 2 minutes. The predicted
      distribution of the PET activities and the proton dose distributions in the
      patients were also calculated using Monte Carlo (MC). Along the beam direction,
      the 50% fall-off positions of the maximum PET activity at each line profile were
      compared with the MC simulated and the measured PET images, and then the
      differences were assessed with root-mean-square deviation (RMSD) and mapped in
      the beam's eye view. RESULTS: The measured PET images showed a good spatial
      correlation with the simulated PET images and the proton dose distributions even
      though the treated volumes and locations varied between patients. The RMSD
      values, representing the surface differences between the measured and simulated
      PET, were assessed to be 4.3-5.1 mm for four patients. Some region including the
      penumbra showed larger differences but was excluded. CONCLUSIONS: We have
      explored the potential of the in-room PET for proton therapy monitoring through a
      clinical trial. The PET image analysis method based on MC simulations showed that
      the distal dose surface could be determined within a few millimeters but not
      within the aimed accuracy of 2-3 mm. Improvements in PET-CT image registration
      and biological washout modeling will most likely increase the accuracy further.
      NIH/NCI P01 CA021239.

PMID- 28517509
TI  - SU-E-T-620: Computational Boundary Sampling to Accelerate IMRT Optimization.
AB  - PURPOSE: To reduce the time and memory requirements of Intensity Modulated
      Radiation Therapy (IMRT) treatment planning. METHODS: We propose a new sampling
      method, called Computational Boundary Sampling (CBS) for IMRT optimization, which
      samples all the boundary voxels and a certain percentage of inner voxels of each
      region of interest (ROI). Within CBS, we developed a grid-based sampling method
      for choosing inner voxels. In this method, each region is first evenly gridded
      and then sampling points are randomly selected from each sub-volume. We also
      developed a supporting theory to quantify the solution quality of CBS. We
      compared a variant of CBS that always keeps boundary voxels and a variant of CBS
      that does not. Finally, we quantified the impact of CBS on 10 different
      anonymized, clinical treatment cases using a prioritized prescription
      optimization method, including compute time, required memory and objective
      function values. RESULTS: (1) We have found that the D95 of the targets are
      generally 4% larger when boundary voxels are included. (2) Grid sampling,
      compared to completely random sampling, yields more uniformly distributed
      sampling, with better solution quality, and less variance between independent
      runs, using the same or less time. (3) We have compared our original IMRT
      optimization solver without sampling and the solver combined with CBS sampling.
      The result showed that CBS can reduce the solution time and memory consumption by
      up to 20x with < 2% change in dosimetric variables. CONCLUSIONS: We have proposed
      a new sampling method (CBS), along with corresponding new techniques including
      boundary sampling and grid sampling, to improve time and space efficiency of IMRT
      optimization. A corresponding theory is developed to quantify the error bound.
      Experimental results have shown that our new methods significantly reduce
      solution time and memory costs with negligible impact on resulting plan quality.

PMID- 28517510
TI  - MO-A-217BCD-01: Internal Emitter Dose Estimation.
AB  - : Tissue absorbed dose (D) is a computed result for internal emitters. For fixed
      geometries, D is calculated by a matrix (S) multiplication of the integrated
      activity vector (A). The last quantity is usually measured by nuclear imaging of
      activity in various source organs and performing a temporal integration. A is the
      same as the total number of source decays. Dose is computed for a number of
      target organs - some of which will be the same as the source organs. The D = S*A
      relationship is general in that the same formula may also be used for voxels
      within organs or even down to the cellular level. Finding the activity (A) in
      source tissues may be done by a number of methods of which 6 are described. The
      most common clinical technique is the geometric mean (GM) image of an organ.
      Uncertainties in the GM method are ~ +/- 30%. If one can do quantitative SPECT,
      PET or CAMI imaging, the variation is reduced to around +/- 6%. These last three
      techniques, however, require fusion of anatomic (e.g. CT) and nuclear images. The
      S matrix is generated via Monte Carlo methods and may be used in two formats. The
      most common is a set of phantom-derived values for regulatory or scientific
      considerations. An example is the OLINDA program from Vanderbilt University. In
      this case, the corresponding animal or patient A value must be normalized using
      blood flow arguments. A second format is modification of a phantom's S values for
      a particular patient using the latter's geometry as found in CT or MRI scans.
      Corrections in such cases may be 2-fold or more because of patient organ size
      variability. These variations may be due to genetic reasons and/or disease. Two
      caveats to the use of the above dose formulation should be mentioned. One
      exception is that the geometry may vary during tissue irradiation; e.g., by tumor
      size decrease due to immediate radiation dose effects. In this case, the standard
      formula is replaced by its differential form: dD/dt = S(t)*A(t). Dose rate may
      also be an important biological factor in assessing tissue response. A second
      important biological consideration is that effects - such as tumor regression -
      may depend upon higher powers of D than the first. Thus, the tissue response may
      not be a linear function of D, but would exhibit a sigmoid shape. One would
      anticipate such responses due to saturation of a biological system. LEARNING
      OBJECTIVES: 1. Knowing the general formula for internal emitter absorbed dose
      estimation. 2. Understanding the various methods used to measure activity, at
      depth, in source organs in a living animal or patient. 3. Realizing that two
      types of dose may be computed: one for a phantom and a second type for an
      individual patient. S values must be modified accordingly for these two
      computations. 4. Estimating uncertainties - including those in both A and S -
      involved in the dose estimation process.

PMID- 28517511
TI  - SU-E-T-632: Metrics for Comparing Dose Volume Histograms.
AB  - PURPOSE: The process of IMRT planning is an iterative inverse process, where a
      planner seeks to attain a desired dose distribution, specified for tumors and
      OARs, hence creating a plethora of competing constraints. However, the final
      product is rather the unpredictable outcome of a series of trial-and-error
      attempts at meeting these competing objectives. A key tool to inspect the quality
      of a plan is the DVH. We provide a set of metrics for unbiased DVH comparison.
      METHODS: The treatment of one prostate case was planned by seven planners, while
      imposing the same clinical objectives for PTV and OARs. The resulting seven DVHs
      were compared based on their deviation of from the ideal coverage, namely 100% of
      PTV receiving 100% of the dose. Our deviation function L measures the area
      between the ideal and realized DVH. A weight function W is used for dose
      dependency. We employ a set of Ws: constant, piece-wise linear, quadratic, normal
      and beta-distributional. RESULTS: We show that the deviation of some planners are
      consistently higher than others for all eight Ws. Similarly, we observe that one
      of the planners consistently exhibits the lowest deviation, while another one is
      low for linear and quadratic Ws and worsen for the distributional functions
      independent of their slope and range. Further, the normal and beta-density
      function weights, as they primarily penalize the range of 95% < Dose < 105%,
      hence discriminating only deviations in the respective region. CONCLUSIONS: The
      outcome of treatment planning is strongly related to the planning personal. The
      proposed set of DVH metrics allow for unbiased comparison, beyond the visual
      inspections. An optimized superposition of these metrics may yield a practical
      tool for daily treatment planning. Furthermore, these results exhibit the need
      for methods whose outcomes are independent of the planning personal.

PMID- 28517512
TI  - MO-A-213AB-09: Hypofractionated Proton Therapy of the Prostate: The Impact of the
      Uncertainties in Dose Delivery and Alpha/Beta Ratio on Tumor Dose Escalation.
AB  - PURPOSE: Hypofractionation is expected to improve therapeutic ratio for prostate
      radiotherapy, due to the relatively low alpha/beta ratio of the prostate tumor
      (~1.2 to 2.0 Gy). However, the gain in tumor equivalent dose in 2-Gy fractions
      (EQD2) is accompanied by the increased uncertainty in delivered dose due to inter
      fractional variations. The purpose of this study is to evaluate how this trade
      off is affected by the uncertainty of the tumor alpha/beta. METHODS: We used
      serial CT images acquired from two prostate cancer patients. Target and normal
      organs were contoured on the simulation and daily images. A 3D conformal proton
      plan was designed based on standard fractionation (78 Gy in 39 fractions) and
      renormalized for hypofractionation (between 5 and 28 fractions). The fraction
      size of the hypofractionated protocols was adjusted so as to maintain the maximum
      rectal dose at 78 Gy-EQD2 (alpha/beta = 3 Gy). The fractional dose, calculated on
      each daily CT, was mapped to the simulation geometry via deformable registration.
      The worst-case-scenario PTV dose for a hypofractionated protocol was estimated by
      summing the fractions (e.g., 28) with the lowest D97%. The target dose (e.g.,
      D100%) was evaluated for alpha/beta of 1.2 to 2.0 Gy. RESULTS: The dose delivery
      uncertainty due to inter-fractional motion increased as the treatment became more
      hypofractionated. D100% was<78 Gy-EQD2 for protocols with 28, 26, 23 and 20
      fractions when alpha/beta was >1.25, 1.46, 1.68 and 1.84 Gy, respectively. At
      alpha/beta of 2 Gy (1.2 Gy), D99% ranged from ~79 (81) to 85 (98) Gy-EQD2 for
      treatments in 28 to 5 fractions. Below D97%, the target dose was predominantly
      determined by alpha/beta, and the motion impact was minimal. CONCLUSIONS: In
      prostate treatments, the impact of inter-fractional motion on tumor dose
      escalation is small for alpha/beta <2.0 Gy, and is of minimal concern to
      hypofractionated proton therapy. This study was supported by the Federal Share of
      program income earned by Massachusetts General Hospital on C06-CA059267, Proton
      Therapy Research and Treatment Center.

PMID- 28517513
TI  - SU-E-T-643: Optimum Beam Parameters for Lung SBRT Volumetric Arc Treatment.
AB  - PURPOSE: We present an analysis of the variation in acceptable SBRT lung plans
      with beam parameters. A figure of merit encompassing standard metrics is used for
      analytical comparison to determine the optimum plan quality. METHODS: A set of
      optimization dose-volume constraints was formulated that consistently produced
      acceptable plans. Plans were normalized to deliver a prescription dose (PD) of
      5000 cGy to 95% of the PTV volume. The Conformity Index (CI), Conformity Number
      (CN), and Gradient Index (GI), and mean GTV dose (MDgtv) were calculated. In SBRT
      hotspots near the target center are often deemed acceptable. The ratio MDgtv/PD
      is greater then 1.0 and larger values indicate that more dose is delivered where
      desired within the PTV. We combine the indices into a single figure of merit, FOM
      = (1/CI)*CN*(1/GI)*(MDgtv/PD), for which larger values indicate better plan
      quality dosimetrically. FOM values were normalized to 1.0 for the best plan.
      Twenty four plans were calculated for 6X, 6X flattening filter free (FFF), 10X,
      and 10X FFF photon beams. The gantry arc rotations were 0 degrees -180 degrees 
      (180arc), 135 degrees -30 degrees  (255arc), and 181 degrees -179 degrees 
      (360arc). The couch angle was either 0 degrees  (coplanar) or +/- 15 degrees 
      (non-coplanar). RESULTS: For the normal lung volume there was no significant
      variation in either mean dose or percent volume receiving 2000 cGy. However, the
      percent volume receiving 500 cGy varies significantly with energy and couch
      angle. Ninety six plan quality indices were tabulated. Overall, the 6X FFF non
      coplanar beam with a 255 degree arc gave the best the figure of merit; it was
      6.5% higher then nearest competitor largely due to superior conformality.
      CONCLUSIONS: Individual plan quality indices were combined into a single figure
      of merit for various beam parameters that can be used to analytically select the
      optimum dosimetric plan.

PMID- 28517514
TI  - SU-F-BRCD-05: Mean Regional Dose to the Esophagus Predicts Acute Toxicity Rate
      for Lung Cancer Patients.
AB  - PURPOSE: The relationship between spatial aspects of the dose distribution and
      incidence of acute radiation esophagitis for non-small-cell lung cancer (NSCLC)
      patients is not well understood. Specifically, the location of dose along the
      superior-inferior (SI) axis of the esophagus has not been previously considered.
      We introduce the concept of mean regional dose (MRD) calculated for esophageal
      subvolumes, and test for significance for prediction of acute esophagitis (AE).
      METHODS: The 3D dose distribution within the esophagus was extracted for 541
      NSCLC patients treated with definitive photon therapy. The esophagus contour was
      divided into equal geometric halves, thirds, and fourths along the SI direction
      of the structure. MRD in each subvolume was calculated. Univariate logistic
      regression was performed to determine the correlation between MRD and CTCAE3.0 AE
      grade = 2 (medical intervention). The MRD was incorporated into an existing NTCP
      model (based on mean dose for the total esophageal volume) as a separate additive
      factor. RESULTS: Univariate analysis indicated a significant correlation between
      AE grade = 2 and MRD in each of the esophageal subvolumes except for the inferior
      third and inferior-most quarter. There was a statistically significant
      improvement when including the additive MRD factor for the superior/inferior
      halves, superior/inferior thirds, and superior-most/inferior-most quarters into
      the NTCP model. CONCLUSIONS: This study investigates previously unexplored
      regional differences in delivered dose to the esophagus of patients treated for
      NSCLC. There is evidence to suggest that dose to the superior portions of the
      esophagus is more important as it relates to the potential for acute toxicity.
      The 541 patient cohort is the largest database used to investigate AE in patients
      treated for NSCLC, strengthening the power of the statistical results. Additional
      methods to incorporate dose in individual esophagus voxels (along the SI axis)
      into the NTCP model are also being explored.

PMID- 28517515
TI  - SU-E-T-624: Comparison of PTV+PRV-Based Optimization and Robust Optimization in
      Intensity-Modulated Proton Therapy.
AB  - PURPOSE: Robust optimization leads to IMPT plans that are more robust than and
      superior in optimality compared to PTV-based optimized plans. Robust optimization
      incorporates setup and range uncertainties, which implicitly adds margins to
      targets and organs-at-risk (OARs); whereas PTV-based optimization only considers
      setup uncertainties and adds margins only to targets in practice. The purpose of
      this work is to determine if the superiority of robustly optimized plans is due
      to not assigning margins to OARs during PTV-based optimization. METHODS: Plan
      robustness and optimality of the PTV plus Planning organs-at-Risk Volume (PRVs)
      based plans and robustly optimized plans were compared for 5 head and neck cancer
      cases and one rhabdomyosarcoma case. The PRVs were generated by expansion from
      OARs by 3 mm. 9 different dose distributions were computed - one each for +/-
      setup uncertainties along three spatial directions, for +/- range uncertainty,
      and the nominal dose distribution. The worst-case dose distribution was obtained
      by assigning the lowest dose among the 9 doses to each voxel in the target and
      the highest dose to each voxel outside the target. The DVHs from the worst-case
      dose were used to assess the plan optimality and robustness. D1cc doses for
      spinal cord and brainstem, mean doses Dmean for oral cavity and parotids, and D1%
      doses for other organs were also used to assess plan optimality. D5% and D95%
      doses are used to assess target dose coverage and homogeneity. RESULTS: For H&N
      cases, PTV+PRV-based optimization was inferior to robust optimization. However,
      PTV+PRV-based optimization yielded plans that spared OARs better than PTV-based
      optimization, although the target dose robustness and homogeneity were comparable
      to the PTV-based optimization. The same conclusions are also valid in the
      rhabdomyosarcoma case. CONCLUSIONS: We find that the PTV+PRV method can partly
      improve plan optimality, but it is still inferior to robust optimization method.
      This research is supported by National Cancer Institute (NCI) grant P01CA021239,
      the University Cancer Foundation via the Institutional Research Grant program at
      the University of Texas MD Anderson Cancer Center, and MD Andersona?TMs cancer
      center support grant CA016672.

PMID- 28517516
TI  - MO-A-213AB-02: Redesign of a 6 MV Linear Accelerator Waveguide to Produce
      Energies Up to 10 MV.
AB  - PURPOSE: To investigate the feasibility of producing a short, high-energy linear
      accelerator for use in a proposed hybrid linear accelerator magnetic resonance
      imager (linac-MRI). METHODS: A short 6MV waveguide was previously simulated in
      COMSOL and benchmarked against experiment. The simulated input power is increased
      from 2.5 to 7.5 MW to reflect replacing the magnetron power source with a
      commercially available klystron, and the RF fields within the waveguide are
      calculated. The RF solution is used as an input into PARMELA, an electron
      tracking software, to calculate the electron energy and spatial distribution
      exiting the waveguide. The electric fields within the waveguide are compared with
      experimental thresholds for electric breakdown within the waveguide to determine
      the possibility of operation at increased input power. The energy spectrum of the
      electron beam incident on the target is analyzed for suitability for
      radiotherapy. Finally, some potential modifications to the simulated cavity
      dimensions and positioning are discussed, and a preliminary estimate of the
      effects on the electron distributions are analyzed. RESULTS: When the input power
      is increased, peak surface electric fields within the waveguide of 215 MV/m are
      calculated, below the threshold determined by experiment of 240 - 300 MV/m for
      similar resonant structures. The FWHM of the electron focal spot is shown to be
      1.5 times larger than the focal spot from the unmodified waveguide. The maximum
      electron energy increases from 6.1 to 10.6 MeV and the spread of electron
      energies is 5 times larger than the original. The modifications to the first
      cavity are shown to reduce the focal spot and energy spread to be comparable to
      the unmodified waveguide. CONCLUSIONS: It is feasible to produce a high-energy
      waveguide that is short enough for use in our linac-MRI. Slight modifications to
      the existing waveguide design will be required to optimize beam parameters for
      treatment. ACF Graduate Studentship.

PMID- 28517517
TI  - SU-E-T-636: Comparison of RapidArc-Based Radiosurgery with Cone-Based Cyberknife
      Treatment for Multiple Intracranial Tumors.
AB  - PURPOSE: To investigate the feasibility of RapidArc technique on intracranial
      radiosurgery for multiple lesions. METHODS: Six patients who were previously
      treated using cone-based technique, Cyberknife were included in this study. These
      patients have multiple lesions (6-9, mostly metastasis). In our current clinical
      practice, each lesion was planned and treated individually. The prescription was
      15-21 Gy at 80% with single fraction. These cases were replanned with RapidArc on
      the platform of Varian Truebeam STx equipped with high resolution MLC leaves of
      2.5mm at center. The maximum dose rate is 1400 MU/min at 6 MV for flattering
      filter free mode. Because of long span of multiple lesions, the targets were
      divided into two groups with two isocenters. Each plan with one isocenter
      contains 4 non-coplanar arcs, and dose optimization was performed with the two
      plans combined. Critical organs, such as eyes, brainstem and brain were
      constrained. The individual Cyberknife plans were summed to compare with the
      RapidArc plan. Scenarios of setup error were simulated during RapidArc treatment.
      RESULTS: RapidArc plans can achieve comparable target coverage and normal tissue
      avoidance to Cyberknife plans. The brain dose volume histogram (DVH) curves of
      the two techniques are similar in spite of different appearance of their 3D dose
      distributions. MU is much higher for summed Cyberknife plan. Because RapidArc can
      treat several lesions together, the complete treatment time for all lesions is
      significantly reduced. However RapidArc treatment is susceptible to setup error,
      which may cause increase in normal tissue dose and decrease in target dose
      coverage. The level of discrepancy depends on the magnitude of setup error,
      location and dose distribution of the target. CONCLUSION: Multiple brain lesions
      treatment with RapidArc radiosurgery is clinically feasible with setup error
      fully accounted. It can provide dose performance comparable to cone-based
      Cyberknife treatment.

PMID- 28517518
TI  - MO-A-BRB-02: Facts and Fiction of Flattening Filter Free (FF-FFF) X-Rays Beams.
AB  - : The primary purpose of the FFF X-rays is to provide much higher dose rates
      available for treatments. For example, FFF X-rays from Varian TrueBEAM can
      deliver 1400 MU/minute for 6 MV X-rays and 2400 MU/minutes for 10 MV X-rays.
      Higher dose rates have definite clinical benefits in organ motion management. For
      example, larger dose fractions can be delivered in a single breath-hold or gated
      portion of a breathing cycle. In SRS or SBRT treatments, large MUs are often
      required and FFF X-ray beams can deliver these large MUs in much shorter "beam
      on" time. With shorten treatment time, these FFF X-rays improve patient comfort
      and dose delivery accuracy. FFF X-ray beams may become one of the necessary
      equipment configurations for SBRT and/or SRS treatments, in the future. This
      presentation will address some unique issues dealing with the FFF X-rays: (1)
      FIELD SIZES flattening Filter Free (FFF) X-ray beam has been in clinical use for
      quite some time. However, not until recently, these FFF beams are used in
      limited, small field sizes, for example, in Tomotherapy and CyberKnife
      machines.Varian TrueBEAM allows the FFF X-ray beam to have up to 40 * 40 cm field
      sizes for both 6 and 10 MV X-rays (15 MV FFF X-rays are not yet released for
      clinical use). For large treatment fields, the dose uniformity within an
      irradiated treatment field will need to be "modulated" by MLC movements (IMRT) to
      cut down the higher beam intensity near the central portion of the FFF X-ray
      beam. Thus, larger MUs are required compared with a conventional (flattened) X
      ray beam. Or, MLC movements (EVIRT) are now being used to "flatten" the FFF X
      rays to provide dose uniformity within those large PTVs. The high dose rates from
      the FFF X-rays are now being off-set by the larger MUs requirements. Therefore,
      FFF X-rays can bring clinical advantages over conventional X-rays when used with
      small field sizes, such as in SBRT and/or SRS applications. (2) DOSEVIETRY
      MEASUREMENT EQUIMENT: Because of the more than 2 to 4 fold increases in dose rate
      (MU/minute), the radiation measurement equipment and techniques need to be
      carefully evaluated, such as ionization chamber characteristics, electrometers,
      scanning equipment. First comes to mind is the ion-recombination characteristics
      of the ionization chamber (P-ion). This will determine the accuracies of the
      measured percentage depth doses and penumbra of these FFF X-ray fields. And, it
      will also affect the absolute dose measurements (Gy/MU) using the TG-51
      formulations. The measured PDDs and profiles should be corrected for the P-ion
      effect. However, it is not a simple task for physicists to perform the P-ion
      corrections for PDDs and profiles using the presently available methods
      associated in commercial 3-D scanning equipment and algorithm. It may become
      necessary for physicists to adapt and get accustom to the use of "standard beam
      data" provided by manufacturers in the future. In addition, because of the use of
      FFF X-rays are focused on SBRT and/or SRS applications, beam data acquisition,
      scanning techniques, and beam modeling are vitally important. There are many
      publications addressing the "output factors" from small fields, but none pay
      enough attention to the penumbra characteristics of these small X-ray beams.
      Because of the proximity to critical organs, the penumbra characteristics of
      small fields are often more clinically important than output factors. FFF X-rays
      play an important role in SBRT and SRS applications. Therefore, careful penumbra
      measurements should be addressed. Again, it may become necessary for physicists
      to adapt the use of "standard beam data" provided by manufacturers. (3) RADIO
      BIOLOGICAL QUESTION: Though there is a lack of controlled clinical studies with
      FFF X-ray beams, there are several scientific articles addressing the
      radiobiological concerns of high dose rate deliveries, especially when it is used
      to deliver large doses per fraction, such as 10 Gy/faction. This type of dose per
      fraction is often used in SBRT or SRS treatments. Radiobiological concerns are
      not in the cell kill effect within the target volume. It is the normal tissue
      damages surrounding the target. There are concerns about the late toxicities of
      these high dose rate and high dose per fraction deliveries using FFF X-ray beams.
      (4) SKIN (ENTRANCE) DOSE DISCUSSIONS: In conventional X-ray beams, the low energy
      components of the X-ray beam are removed by the in-line X-ray flattening filter.
      But, in Flatten Filter Free X-ray beams, these low energy components are exiting
      the X-ray collimators. This is clearly documented by the difference in the
      percentage depth doses for these FFF X-ray beams. The FFF X-ray beams have a
      lower "effective energy" compared to conventional X-rays. Therefore, it is
      important to study the skin (entrance) dose from these FFF X-rays. In the
      literature, reported skin (entrance) doses from different linear accelerator
      manufacturers vary widely. Skin doses from Varian TrueBEAM have been studied and
      have found to be marginally higher than the conventional X-rays. However this
      margin increase is not clinically significant.(5) Summary / conclusions /
      discussions: The FFF X-rays improve the treatment delivery by their very high
      dose rates (1400 and 2400 MU/minute) and shortened treatment time. FFF X-ray
      beams are most applicable and the high dose rates are most advantageous when the
      treatment field sizes are small. The dosimetry of FFF-X-rays is made more complex
      by the P-ion determination and necessary corrections to X-ray beam percentage
      depth doses and profiles. There are radiobiological concerns about late toxicity
      of normal tissue irradiated by FFF X-rays when large dose per faction treatment
      applications are used. There are wide ranges of skin doses from these FFF X-rays
      reported in the literature. LEARNING OBJECTIVES: 1. Flattening Filter Free X-rays
      have been in clinical use for many years but mostly for small field sizes. 2.
      Flattening Filter Free X-rays have significantly shorter treatment time if is
      used for small field applications, such as: SBRT or SRS. 3. Because of the high
      dose rate (MU/minute), dosimetric properties of these FFF X-rays need to be
      carefully studied. Ion-recombination of ionization chambers is a concern. Beam
      data acquisition, beam modeling, and absolute dosimetry need to be done with
      great care, especially in small field applications. 4. Late toxicities of normal
      tissue may be a concern and need to be studied by organized clinical protocols.

PMID- 28517519
TI  - SU-E-T-647: Plan Quality in Computerized Non-Coplanar IMRT Beam Angle
      Optimization is Highly Dependent on the Extent of the Beam direction Search
      Space.
AB  - PURPOSE: To investigate the relationship between plan quality and the extent of
      the beam direction search space in computerized beam angle selection for
      generating optimal (non-coplanar) IMRT plans for prostate SBRT with dose
      distributions simulating HDR brachytherapy. METHODS: iCycle (1) was used to
      investigate the relationship between plan quality and the extent of the set of
      beam directions available for plan generation. For a group of 10 prostate
      patients, optimal plans were generated for 5 direction search spaces. For
      coplanar treatments (CP set), 72 orientations were available for selection
      (separation 5 degrees ). The fully non-coplanar set (F-NCP) included the CP
      directions plus 430 directions spread over the sphere. The CK set contained the
      directions available at the robotic Cyberknife unit. CK+ and CK++ were extensions
      of CK to investigate some of its characteristics. Generated plans were in
      accordance with our clinical SBRT protocol for Cyberknife treatment, delivering 4
      fractions of 9.5 Gy. Adequate PTV coverage had the highest priority. Reduction of
      rectum dose was the highest OAR priority. RESULTS: The mean PTV coverage (V95) of
      all SBRT plans was 99% i,+/- 0.9% (1 SD). F-NCP plans had most favorable OAR dose
      parameters, while for coplanar plans OAR doses were highest. Compared to coplanar
      treatment, rectum Dmean/V60 were 25% / 37% and 19% / 21% lower in F-NCP and CK
      plans. Higher rectum dose for the Cyberknife set compared to F-NCP was not caused
      by a lack of posterior beams for Cyberknife. For all search spaces, reduction in
      OAR dose only leveled off with > 20 beams in the plans (for CP, rectum V60 in 25
      beam plans was reduced by 64% compared to 11 beams). In the non-coplanar set-ups,
      there was a preference for beams with a (large) lateral component. CONCLUSIONS:
      Plan quality clearly improved with the extent of the beam direction search space
      (coplanar worst), and the number of beam directions in the plan (25 clearly
      better than 11).(1) Breedveld S, Storchi P, Voet P, Heijmen B, Med Phys 2012;
      DOI: 10.1118/1.3676689.

PMID- 28517520
TI  - SU-F-BRCD-09: Total Variation (TV) Based Fast Convergent Iterative CBCT
      Reconstruction with GPU Acceleration.
AB  - PURPOSE: To improve image quality and reduce imaging dose in CBCT for radiation
      therapy applications and to realize near real-time image reconstruction based on
      use of a fast convergence iterative algorithm and acceleration by multi-GPUs.
      METHODS: An iterative image reconstruction that sought to minimize a weighted
      least squares cost function that employed total variation (TV) regularization was
      employed to mitigate projection data incompleteness and noise. To achieve rapid
      3D image reconstruction (< 1 min), a highly optimized multiple-GPU implementation
      of the algorithm was developed. The convergence rate and reconstruction accuracy
      were evaluated using a modified 3D Shepp-Logan digital phantom and a Catphan-600
      physical phantom. The reconstructed images were compared with the clinical FDK
      reconstruction results. RESULTS: Digital phantom studies showed that only 15
      iterations and 60 iterations are needed to achieve algorithm convergence for 360
      view and 60-view cases, respectively. The RMSE was reduced to 10-4 and 10-2,
      respectively, by using 15 iterations for each case. Our algorithm required 5.4s
      to complete one iteration for the 60-view case using one Tesla C2075 GPU. The few
      view study indicated that our iterative algorithm has great potential to reduce
      the imaging dose and preserve good image quality. For the physical Catphan
      studies, the images obtained from the iterative algorithm possessed better
      spatial resolution and higher SNRs than those obtained from by use of a clinical
      FDK reconstruction algorithm. CONCLUSIONS: We have developed a fast convergence
      iterative algorithm for CBCT image reconstruction. The developed algorithm
      yielded images with better spatial resolution and higher SNR than those produced
      by a commercial FDK tool. In addition, from the few-view study, the iterative
      algorithm has shown great potential for significantly reducing imaging dose. We
      expect that the developed reconstruction approach will facilitate applications
      including IGART and patient daily CBCT-based treatment localization.

PMID- 28517521
TI  - SU-E-T-628: A Cloud Computing Based Multi-Objective Optimization Method for
      Inverse Treatment Planning.
AB  - PURPOSE: Multi-objective (MO) plan optimization entails generation of an enormous
      number of IMRT or VMAT plans constituting the Pareto surface, which presents a
      computationally challenging task. The purpose of this work is to overcome the
      hurdle by developing an efficient MO method using emerging cloud computing
      platform. METHODS: As a backbone of cloud computing for optimizing inverse
      treatment planning, Amazon Elastic Compute Cloud with a master node (17.1 GB
      memory, 2 virtual cores, 420 GB instance storage, 64-bit platform) is used. The
      master node is able to scale seamlessly a number of working group instances,
      called workers, based on the user-defined setting account for MO functions in
      clinical setting. Each worker solved the objective function with an efficient
      sparse decomposition method. The workers are automatically terminated if there
      are finished tasks. The optimized plans are archived to the master node to
      generate the Pareto solution set. Three clinical cases have been planned using
      the developed MO IMRT and VMAT planning tools to demonstrate the advantages of
      the proposed method. RESULTS: The target dose coverage and critical structure
      sparing of plans are comparable obtained using the cloud computing platform are
      identical to that obtained using desktop PC (Intel Xeon(r) CPU 2.33GHz, 8GB
      memory). It is found that the MO planning speeds up the processing of obtaining
      the Pareto set substantially for both types of plans. The speedup scales
      approximately linearly with the number of nodes used for computing. With the use
      of N nodes, the computational time is reduced by the fitting model, 0.2+2.3/N,
      with r2>0.99, on average of the cases making real-time MO planning possible.
      CONCLUSIONS: A cloud computing infrastructure is developed for MO optimization.
      The algorithm substantially improves the speed of inverse plan optimization. The
      platform is valuable for both MO planning and future off- or on-line adaptive re
      planning.

PMID- 28517522
TI  - MO-A-213AB-06: Validation of Nuclear Reaction Models to Simulate Proton Therapy
      Range Verification Using Prompt Gamma-Rays.
AB  - PURPOSE: The impact of nuclear reaction model differences on simulation of prompt
      gamma-ray imaging for proton therapy range verification was assessed. Four
      nuclear reaction models were used to simulate gamma emission in proton beams, and
      were validated against experimental cross-sections. METHODS: Proton-induced
      nuclear reactions on carbon, oxygen, nitrogen and calcium were investigated with
      the Monte Carlo toolkits GEANT4 9.5 and MCNPX 2.7, and the dedicated nuclear
      reaction codes TALYS 1.4 and EMPIRE 3.1. Absolute cross-sections of discrete
      prompt gamma lines and the total gamma production were obtained for the 1-200 MeV
      incident proton energy range. They were compared to 34 discrete line measurements
      reported in literature. Using these cross-sections, we analyzed the gamma
      production along the path of proton beams passing through various tissues.
      RESULTS: The differences in absolute discrete line cross-sections as predicted by
      the models ranged from almost zero to an order of magnitude, depending on the
      gamma line and incident proton energy. Overall, the dedicated nuclear reaction
      codes provided a better fit to most experimental excitation functions. For a 150
      MeV proton beam stopping in soft tissue, these differences amount to a variation
      by a factor of 4 of the gamma emission around the Bragg peak location. The
      maximum of gamma production near the end of proton range differed by 7 mm, and
      the change of the 50% emission fall-off position was 4 mm. CONCLUSIONS: There is
      a clear need for improvement of nuclear reaction models to accurately simulate
      proton range verification using prompt gamma-rays. Current simulation codes show
      large uncertainties in both the total gamma yield and the correlation of gamma
      emission with the proton Bragg peak. GEANT4 and MCNPX in particular appear to
      have limited predictive power.

PMID- 28517523
TI  - SU-E-T-640: Development of Liver SBRT Planning and Delivery at the Mean
      Respiratory Position Using Deformable Image Registration.
AB  - PURPOSE: Deformable image registration (DIR) allows modeling of liver tumors on
      respiratory correlated (4D) imaging. The mid-position CT was reconstructed for
      liver SBRT plans using DIR, and the potential for dose-escalation was
      investigated. METHODS: Thirty patients were planned clinically with IMRT for 27
      48 Gy in 6 fractions on static exhale 4DCT with PTVs encompassing the breathing
      amplitude. For research, exhale 4DCT was deformed to the inhale 4DCT using
      biomechanical DIR. The mid-position CT was created by applying a percentage (the
      time-averaged normalized position between exhale and inhale calculated from daily
      4D cone-beam CT) to this deformation map, assuming a linear trajectory. A
      probability-based PTV margin, using patient-specific breathing amplitude from DIR
      of 4DCT, was created around the GTV on the mid-position CT where IMRT was re
      optimized. Dose was maximally escalated according to clinical protocol (e.g.
      liver NTCP <5%). The 4D predicted breathing dose was accumulated by interpolating
      the elements' positions at exhale, mid-position and inhale onto the respective
      dose matrices (weighted by time spent nearest each matrix) then summed. RESULTS:
      Compared the exhale plans, the GTV-to-PTV volume decreased on the mid-position
      plans by a mean of 31% (p<0.01, range: 24-38%). Static re-planning on the mid
      position CT decreased the mean effective liver volume by 7% (p=0.032), enabling
      escalation of the nominal prescribed dose in 80% of patients of 6-12 Gy.
      Reconstruction of the 4D predicted breathing dose resulted in a mean increase of
      6.7 Gy (p<0.01, maximum increase of 15.0 Gy) in mean GTV dose for the mid
      position versus the exhale plan. For the mid-position plan, the minimum 0.5 cm3
      GTV dose received 100% of the prescription in the 4D distribution. CONCLUSIONS:
      Liver SBRT Planning at the mean respiratory position enables PTV reduction and a
      mean dose escalation of 6.7 Gy, potentially improving local control. Dr. Brock
      has financial interest in deformable registration technology through the
      licensing of Morfeus to RaySearch Laboratories. Research is funded by NIH
      1R01CA124714.

PMID- 28517524
TI  - SU-E-T-631: Beam Geometry Selection Using Sequential Beam Addition.
AB  - PURPOSE: To investigate a beam geometry selection algorithm based on sequential
      addition of beams. METHODS: The sequential beam addition algorithm (SBA) requires
      an objective function (score) and a set of candidate beam geometries (pool). The
      optimal score is determined for each beam in the pool and the best beam selected.
      Scores are then calculated for the selected beam in combination with each member
      of the pool. The pair with the best score is selected and the score again
      determined in combination with each beam in the pool. The process is repeated
      until the desired number of beams is reached. We selected 3 treatment sites,
      breast, lung, and brain, and determined beam arrangements for up to 11 beams from
      a pool comprised of 25 equi-angular transverse beams. For the brain, arrangements
      were additionally selected from a pool of 22 non-coplanar beams. Scores were
      determined for geometries comprised of equi-angular transverse beams (EQA), as
      well as two tangential beams for the breast case. RESULTS: In all cases, SBA
      resulted in scores superior to EQA. The breast case had the strongest dependence
      on beam geometry, for which only 7 beam EQA had a score better than the
      tangential beams, whereas all SBA geometries with more than two beams were
      superior. For the lung case, for both EQA and SBA the scores monotonically
      improved with increasing number of beams; however, SBA required fewer beams to
      achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool
      was equivalent to EQA, while the non-coplanar pool resulted in slightly better
      scores; however, the dose-volume histograms demonstrated that the differences
      were not clinically significant. CONCLUSIONS: For situations in which beam
      geometry has a significant effect on the objective function, SBA can identify
      arrangements equivalent to equi-angular geometries but using fewer beams. Varian
      Medical Systems.

PMID- 28517525
TI  - MO-A-213AB-08: 2D Water Equivalent Path Length Imaging Technique for Pre
      Treatment Range Verification in Proton Therapy.
AB  - PURPOSE: To assess the potentials of a novel detector for providing a
      transmission image of the patient in terms of the Water Equivalent Path Length
      (WEPL) values and to evaluate the detector potential for real-time imaging of
      moving targets. METHODS: The method is based on the principle that for passively
      scattered proton beams the WEPL of any point located in the dose plateau of a
      spread-out Bragg-Peak can be derived from the time dependence of the dose rate
      function measured at this point. A flat-panel 2D detector array (Sun Nuclear
      Corporation, 249 diodes, pitch ~6 mm, 2 ms time resolution) was placed distal to
      a range of phantoms with varying complexities. The dose rate received by all
      diodes were measured as functions of time and analyzed to obtain the WEPL values.
      To assess the potential real-time features of this imaging technique, a Lucite
      cube was imaged while moving with a sinusoidal pattern with the amplitude and
      period comparable to a typical mobile tumor. RESULTS: In water tanks, millimeter
      accuracy in the determination of the WEPL could be achieved and the geometrical
      shape of wedge and sphere phantoms could be reproduced. In more complex phantoms
      such as a Lucite step-like compensator or Medulloblastoma patient compensators,
      multiple Coulomb scattering and range mixing cause a slight deterioration in the
      reconstruction of the WEPL. We found that tracking of a moving target in the
      coronal plane is potentially feasible. CONCLUSIONS: The technique gives less than
      1 cGy of dose to patients and is therefore ideal for 'range-tuning' prior to
      treatment. For clinical applications, the beam for 'tuning' will need a deeper
      range than the prescription and once the radiological path length to the
      dosimeter is determined and compared with that from planning, the proton range
      for the actual treatment can be adjusted.

PMID- 28517526
TI  - SU-E-T-642: Patient Stratification Based on Improvements in Conformity Indices
      and Normal Tissue Sparing with IMRT in Arteriovenous Malformation Treatments.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is a treatment of choice for
      Arteriovenous Malformations (AVMs) in anatomical locations associated with a risk
      of surgical complication. The aim of this study was: 1) to determine which AVM
      patients benefit from IMRT treatment over 3D-Conformal Treatment (3DCRT) based on
      PTV size, shape and normal tissue (NT) dose constraints imposed upon IMRT plans;
      2) to assess optimized dose distributions against prospectively collected data
      for symptomatic radiation injury following SRS. METHODS: 31 patients previously
      treated for AVMs with 3DCRT were replanned with static gantry IMRT. PTV volumes,
      defined as AVM+1mm margin, ranged from <1cc to >25cc. IMRT plans were generated
      for BrainLab microMLC using the iPlan treatment planning system. First, PTV
      constraints were used. The conformity of the dose prescribed to the PTV margin
      was compared between the two plan types for all patients. Second, NT constraints
      were introduced into each IMRT plan at 7Gy and 12Gy. Finally, these dose
      constraints were manipulated to achieve maximum NT sparing while maintaining the
      desired dose coverage of the PTV. RESULTS: Examination of the conformity index
      for an increase of >0.03 showed a separation of patients into those who did and
      did not benefit from IMRT. Some patients who did not have a significant benefit
      from conformity alone showed a reduction in max PTV dose by as much as 9%.
      Moreover, with NT dose constraints, the volume of NT irradiated decreased by a
      considerable amount for a subset of patients by 10-21.8% and 9-16.9% for the 7Gy
      and 12Gy constraints, respectively. CONCLUSIONS: This work indicates the
      potential for significant dose reduction to NT surrounding AVMs and provides
      rules to determine which patients are likely to benefit from IMRT. By utilizing
      IMRT plans, with and without dose constraints, NT sparing can be improved and
      risk of symptomatic injury reduced.

PMID- 28517527
TI  - SU-F-BRCD-04: Efficient Scatter Distribution Estimation and Correction in CBCT
      Using Concurrent Monte Carlo Fitting.
AB  - PURPOSE: X-ray scatter is a known source of image artifacts, contrast reduction,
      and CT number inaccuracy in cone-beam CT (CBCT). We present and demonstrate the
      performance of a novel scatter correction method based on an algorithm that
      simultaneously combines multiple Monte Carlo (MC) CBCT scatter simulations
      through the use of a fitting function. METHODS AND MATERIALS: The scatter
      estimation system consists of concurrently run MC CBCT scatter projection
      simulations that are a sub-sample of the projection angles used in the
      reconstruction projection set, P, to be corrected. The photons generated by each
      MC simulation are simultaneously aggregated in an algorithm which computes the
      scatter detector response, S(i,j,k), for each down-sampled projection location
      (i,j) and angle (k). S(i,j,k) is fit to a function, FS, and if FS is determined
      to have a specified goodness of fit value the simulations are terminated. FS is
      subtracted from P which is subsequently used to create a scatter corrected
      reconstruction. The scatter correction method was applied to simulated phantoms
      using a frequency limited sum of sines and cosines as the fitting function. Image
      quality in the corrected reconstruction was evaluated using metrics looking at
      contrast, noise, and artifact reduction. RESULTS: Fitting the scatter
      distribution to a limited sum of sine and cosine functions, using a low-pass
      filtered Fast Fourier transform, provides a computationally efficient and
      accurate fit. Scatter distribution estimates for a 360 image projection set were
      computed in under one minute. The scatter correction algorithm increased the
      contrast-to-noise ratio by 46%, reduced the shading artifact by 87%, and
      decreased the skin line artifact by 79% in reconstructions of a simulated pelvis
      phantom. CONCLUSION: The algorithm provides an efficient method for estimating
      and removing the scatter distribution in from CBCT projection images. The results
      on simulated data show a significant increase in image quality.

PMID- 28517528
TI  - SU-E-T-623: Utilizing a Hybrid Optimizer to Improve Dose Conformity during IMRT
      Planning.
AB  - PURPOSE: For IMRT treatment planning, an index-dose based algorithm features a
      fast approach in optimizing beam shapes and weights, and the quasi-Newton method
      is adopted in segment weight optimization by many commercial products. By
      combining these two optimizers, we aim to improve IMRT plan quality by achieving
      better normal tissue sparing. METHODS: An IMRT plan was generated using an in
      house treatment planning system in three steps: 1) optimize fluence using beamlet
      intensity modulation, 2) generate Multi-collimator leaf sequence and segment
      weights, 3) tune the segment shapes and weights as each segment treated as a
      single beam. A quick converge was achieved by the optimizer implementing the
      index-dose concept in step (1 and 3). To further improve the plan's quality, we
      optimized the segment weights via a quasi-Newton gradient search method where a
      convex objective function was constructed using both existing segment shapes and
      dose constraints defined by the planner. Thus, the segment shapes were optimized
      with index-dose, the shapes optimized with quasi-Newton, alternately. The new
      approach was evaluated with patient cases including prostate and head & neck.
      RESULTS: Both plans had equivalent tumor dose coverage. For the prostate case,
      the rectal dose was reduced by 6% for V60% and 2% for V10cc, respectively. For
      the head and neck, better sparing was observed for the spinal cord, the left
      parotid, and the larynx. CONCLUSIONS: Combining index-dose and quasi- newton
      gradient search can effectively improve sparing of normal tissues without
      sacrificing target dose coverage. This work indicates the potential of improving
      treatment plan quality by integrating different optimization methods.

PMID- 28517529
TI  - MO-A-213AB-01: Potential for Focused Low Energy X-Ray Beam for Therapy.
AB  - PURPOSE: Megavoltage photon beams are typically used for therapy because of their
      skin sparing effect. However, a focused low-energy x-ray beam would also be skin
      sparing, and would have a higher dose concentration at the focal spot. Such a
      beam can be produced with polycapillary optics. MCNP5 was used to model dose
      profiles for a scanned focused beam, using measured beam parameters. The
      potential of low energy focused x-ray beams for radiation therapy was assessed.
      METHODS: A polycapillary optic was used to focus the x-ray beam from a tungsten
      source. The optic was characterized and measurements were performed at 50 KV.
      PMMA blocks of varying thicknesses were placed between optic and the focal spot
      to observe any variation in the focusing of the beam after passing through the
      tissue-equivalent material. The measured energy spectrum was used to model the
      focused beam in MCNP5. A source card (SDEF) in MCNP5 was used to simulate the
      converging x-ray beam. Dose calculations were performed inside a breast tissue
      phantom. RESULTS: The measured focal spot size for the polycapillary optic was
      0.2 mm with a depth of field of 5 mm. Focusing was found to remain unchanged
      through 40 mm of phantom thickness. The calculated depth dose curve inside the
      breast tissue showed a dose peak several centimeters below the skin with a sharp
      dose fall off around the focus. The percent dose falls below 10% within 5 mm of
      the focus. Rotating the optic during scanning preserves the skin-sparing effect
      of the focused beam. CONCLUSIONS: Low energy focused x-ray beams could be used to
      irradiate tumors inside soft tissue within 5 cm of the surface.

PMID- 28517530
TI  - SU-E-T-635: Effect of Planning Parameters on Tomotherapy Dosimetric Quality and
      Treatment Efficiency.
AB  - PURPOSE: To investigate how the setting of optimization parameters, fractional
      dose and tuning structure in tomotherapy treatment planning affects plan
      dosimetric quality and treatment efficiency. METHODS: A digital phantom to
      simulate head and neck radiotherapy was constructed for this study. Tumor was
      10cm long C-shaped with two surrounding parallel normal structures (P-NS) and one
      serial normal structure (S-NS). Dose prescription was 54 Gy in total. Fourteen
      treatment plans were generated with varied parameters in five categories: a) jaw
      size (1 to 5cm), b) pitch (0.215 to 0.43), c) modulation factor (1.5 to 4), d)
      dose per fraction (100 to 600cGy) and e) whether to use tuning structure. Plans
      were compared with multiple dosimetric endpoints including target
      minimum/maximum/mean dose, V100%, conformity, heterogeneity, S-NS maximum dose, P
      NS and body mean dose, and treatment times. The reference plan was defined for
      the plan with conventional parameters: jaw 2.5cm, pitch 0.287, modulation factor
      3.0, 200cGy per fraction and use of a 2cm ring structure in optimization.
      RESULTS: Compared with 2.5cm jaw reference plan, 1cm jaw plan decreased the mean
      body dose 10.7% while 5 cm jaw plan increased the dose 17.9%. Smaller pitch
      (p=0.215) made the plan more conform than reference plan, and bigger pitch
      (p=0.43) had opposite effect. A small modulation factor (M=1.5) failed to spare
      critical structures. A medium modulation factor (M=2) resulted in similar plan to
      the reference but with 29% less treatment time. A low fractional dose (100 cGy)
      planned with similar parameter as reference had much inferior target coverage
      (V100%=85.6% vs V100%=96.4). Lastly, the use of tuning structure improved the
      conformity of target. CONCLUSIONS: Selection of optimization parameters in
      tomotherapy treatment planning affects target coverage, critical structure
      sparing, body dose, and treatment time. Target coverage is compromised if
      fractional dose is low to the range of 100 cGy.

PMID- 28517531
TI  - MO-A-BRB-01: Non-Coplanar Rotational Therapy by Using High Efficient Unflattened
      Beams.
AB  - : The rapid dose fall-off from treatment target to the adjacent critical organs
      has been the Holy Grail for radiotherapy treatment planning. The modern treatment
      delivery technologies to address such goal include volumetric modulated
      rotational therapy, non-coplanar EVIRT beams and the use of unflattened beams to
      reduce the penumbra area. In this lecture, the integration of above techniques
      will be presented to achieve the goal of a sharp gradient dose around the target
      and also the discussion of middle to low dose volumes. Use of volumetric
      modulated rotational therapy by multiple non-coplanar arcs is an idea treatment
      modality to focus the high dose in the target area while spreading the low dose
      to even larger volume to reduce the middle range dose to surrounding critical
      organs. This is especially important for SBRT treatment plans since the fraction
      dose is much higher than the traditional fraction schema. The challenges we face
      today are 1. the gantry-couch (patient) collision issue for non-coplanar beam
      angles, 2. the treatment delivery efficiency due to multiple arc rotations and 3.
      the massive inverse optimization computation for multiple rotational arcs can be
      resource intensive and time consuming for treatment plan systems. It might not be
      easy to resolve all the challenges at one time. However, the high efficient
      unflattened beam can certainly improve the delivery speed by reducing the beam-
      on time and this, again, is essential to SBRT patients with high fractional dose.
      In this lecture, the non-coplanar rotational therapy treatment planning
      techniques will be presented and be evaluated by using comformality index,
      gradient index as well as dose volume histogram comparison. The differences in
      treatment delivery time will be tabulated and compared. At the end, the high
      medium-low dose volumes will be illustrated with radiobiological models for the
      philosophy of sun tanned versus sun burned. LEARNING OBJECTIVES: 1. Understand
      treatment plan and dose gradient advantages of using non- coplanar rotational
      therapy 2. Understand potential delivery efficiency by using unflattened beams
      for multiple non-coplanar rotational beams 3. Understand sun tanned versus sun
      burned: the low dose volume and integrated dose.

PMID- 28517533
TI  - SU-F-BRCD-08: Uncertainty Quantification by Generalized Polynomial Chaos for MR
      Guided Laser Induced Thermal Therapy.
AB  - PURPOSE: Magnetic resonance-guided laser induced thermal therapy (MRgLITT) is a
      minimally invasive thermal treatment for metastatic brain lesions, offering an
      alternative to conventional surgery. The purpose of this investigation is to
      incorporate uncertainty quantification (UQ) into the biothermal parameters used
      in the Pennes bioheat transfer equation (BHT), in order to account for imprecise
      values available in the literature. The BHT is a partial differential equation
      commonly used in thermal therapy models. METHODS: MRgLITT was performed on an in
      vivo canine brain in a previous investigation. The canine MRgLITT was modeled
      using the BHT. The BHT has four parameters'" microperfusion, conductivity,
      optical absorption, and optical scattering'"which lack precise measurements in
      living brain and tumor. The uncertainties in the parameters were expressed as
      probability distribution functions derived from literature values. A univariate
      generalized polynomial chaos (gPC) expansion was applied to the stochastic BHT.
      The gPC approach to UQ provides a novel methodology to calculate spatio-temporal
      voxel-wise means and variances of the predicted temperature distributions. The
      performance of the gPC predictions were evaluated retrospectively by comparison
      with MR thermal imaging (MRTI) acquired during the MRgLITT procedure in the
      canine model. The comparison was evaluated with root mean square difference
      (RMSD), isotherm contours, spatial profiles, and z-tests. RESULTS: The peak RMSD
      was ~1.5 standard deviations for microperfusion, conductivity, and optical
      absorption, while optical scattering was ~2.2 standard deviations. Isotherm
      contours and spatial profiles of the simulation's predicted mean plus or minus
      two standard deviations demonstrate the MRTI temperature was enclosed by the
      model's isotherm confidence interval predictions. An a = 0.01 z-test demonstrates
      agreement. CONCLUSIONS: The application of gPC for UQ is a potentially powerful
      means for providing predictive simulations despite poorly known input parameters.
      gPC provides an output that represents the probable distribution of outcomes for
      MRgLITT.

PMID- 28517532
TI  - SU-E-T-646: Feasibility Study of Proton Arc Therapy for the Treatment of Para
      Aortic Lymph Node Tumor.
AB  - PURPOSE: To test feasibility of proton arc therapy (PAT) in the treatment of para
      aortic lymph node tumor and compare its dosimetric properties with advanced
      radiotherapy techniques such as intensity modulated radiation therapy (IMRT) and
      conventional 3D conformal proton beam therapy (PBT). METHODS: The treatment plans
      for para-aortic lymph node tumor were planned for 9 patients treated at our
      institution using IMRT, PBT, and PAT. Feasibility test and dosimetric evaluation
      were based on comparisons of dose volume histograms (DVHs) which reveal mean
      dose, D30%, D60%, D90%, V30%, V60%, V90%, organ equivalent doses (OEDs), normal
      tissue complication probability (NTCP), homogeneity index (HI) and conformity
      index (CI). RESULTS: The average doses delivered by PAT to the liver, kidney,
      small bowel, duodenum, stomach were 7.6%, 3%, 17.3%, 26.7%, and 14.4%, of the
      prescription dose (PD), respectively, which is higher than the doses delivered by
      IMRT (0.4%, 7.2%, 14.2%, 15.9%, and 12.8%, respectively) and PBT (4.9%, 0.5%,
      14.12%, 16.1% 9.9%, respectively). The average homogeneity index and conformity
      index of tumor using PAT were 12.1 and 1.21, respectively which were much better
      than IMRT (21.5 and 1.47, respectively) and comparable to PBT (13.1 and 1.23,
      respectively). The Result shows that both NTCP and OED of PAT are generally lower
      than IMRT and PBT. CONCLUSIONS: This study demonstrates that PAT is better in
      target conformity and homogeneity than IMRT and PBT but worse than IMRT and PBT
      for most of dosimetric factor which indicate that PAT is not recommended for the
      treatment of para-aortic lymph node tumor.

PMID- 28517534
TI  - SU-E-T-627: Optimal Partial Arcs in VMAT Planning.
AB  - PURPOSE: To describe a method for producing minimal delivery time partial arc
      VMAT plans. METHODS: We begin with the assumption that dose quality is the
      primary treatment planning goal. Therefore the first step in the partial arc
      computation is a 180 beam equi-spaced IMRT multi-criteria optimized treatment
      plan, which serves as an ideal plan, along with a set of user- specified
      allowable deviations from this plan. This defines a set of target coverage and
      healthy organ sparing constraints. We then seek a partial arc plan which recovers
      this ideal plan but is minimal in delivery time. The search for the optimal
      partial arc which fulfills the hard constraints is done by wrapping a VMAT
      fluence map optimization/merging/simplification algorithm called VMERGE. The
      search is performed over all possible partial arcs, with start and end locations
      discretized to 20 degree increments, and respecting that the gantry cannot pass
      underneath the couch. This results in 169 partial arcs. For the ones that yield
      feasible plans, the complete VMERGE algorithm is run, which minimizes the
      delivery time for that arc. The minimal delivery time plan that fulfills the
      dosimetric requirements is returned. RESULTS: We apply the method to a lung and
      liver case. The time savings are as follows: (full arc time, optimal partial arc
      time): lung (185 s, 94 s), liver (263 s, 165 s). The optimal arc for the lung
      lesion, a left anterior target, is 140 degrees centered at 50 degrees. The
      optimal arc for the liver lesion is 160 degrees centered at -90 degrees.
      CONCLUSIONS: By wrapping a fast VMAT optimization/sequencing routine by an
      exhaustive search over 169 possible partial arcs, we are able to determine the
      fastest delivery partial arc. The use of partial arcs can significantly shorten
      delivery time in VMAT delivery. The project described was supported by Award
      Number R01CA103904 from the National Cancer Institute. The content is solely the
      responsibility of the authors and does not necessarily represent the ocial views
      of the National Cancer Institute or the National Institutes of Health.

PMID- 28517535
TI  - MO-A-213AB-05: Synthesis of High Quantum Yield Nano-Scintillators for
      Simultaneous Photodynamic Therapy in Radiotherapy.
AB  - PURPOSE: Radioresistant tumors provide one of the biggest challenges for
      improving radiation therapy efficacy. We have demonstrated that semiconductor
      quantum dots can be used as 'impedance matching' devices converting high energy X
      rays to visible photon range for a simultaneous and mechanistically independent
      treatment; photodynamic therapy (PDT). Application of quantum dots was limited by
      it toxicity and relatively low quantum yield with X-ray excitation. To further
      improve the combined therapy strategy, we synthesize and screen for safer and
      more efficient nanoparticles. METHODS: Colloidal GdSe and Gd2O3 nanoparticles
      were synthesized in octadecene using octylamine and oleic acid as surfactants.
      The average diameter of the nanoparticles was 10 nm. The samples in organic
      solution was secured in a light tight box and irradiated by 300 kVp X-rays with a
      dose rate of 300 cGy/min. The visible photon yield is collected by a lens and
      transferred to the photomultiplier tube via optic fibers. The average photon
      counts for 100 seconds were compared between GdSe, Gd2O3 and CdSe quantum dots.
      RESULTS: Different than quantum dots with fixed band gap and emission peaks, the
      fluorescent peaks of GdSe and Gd2O3 were excitation light dependent. Shorter
      emission wavelengths were resulted from higher incident photon energies but the
      spectra overlap well with the Soret band of porphyrin photosensitizers. While
      their fluorescence is substantially weaker compared with QDs under UV excitation,
      fluorescence from both GdSe and Gd2O3 is one order of magnitude stronger than
      that of QD when excited by 300 kV X-rays. CONCLUSIONS: Metal oxide nanoparticle
      scintillators are more efficient X-ray scintillators than Quantum dots. Moreover,
      Metal oxide nanoparticle can utilize the Soret band of photosensitizers for more
      effective energy transfer and excitation. These improvements will reduce the
      required radiation dose and drug concentration for simultaneous photodynamic
      therapy.

PMID- 28517536
TI  - SU-E-T-639: Dosimetric Evaluation of VMAT for the Treatment of NSCLC with SBRT.
AB  - PURPOSE: To demonstrate the dosimetric potential of volumetric modulated arc
      therapy (VMAT) for the treatment of patients with medically inoperable stage I/II
      non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy
      (SBRT). METHODS: Fourteen patients treated with 3D-CRT with varying tumor
      locations, tumor sizes and dose fractionation schemes were chosen for study. The
      target prescription doses were 48 Gy in 4 fractions, 52.5 Gy in 5 fractions, 57.5
      Gy in 5 fractions and 60 Gy in 3 fractions for 2, 5, 1 and 6 patients,
      respectively. VMAT treatment plans with a mix of 2-3 full and/or partial non
      coplanar arcs with 5 degrees -25 degrees  separations were retrospectively
      generated using Eclipse version 10.0. The 3D-CRT and VMAT plans were then
      evaluated by comparing their target dose, critical structure dose, high dose
      spillage, and low dose spillage as defined according to RTOG 0813 and RTOG 0236
      protocols. RESULTS: The VMAT treatment plans yielded an average 9.6-33.7%
      reduction in dose to critical structures and an average 12.0-12.5% increase in
      conformity compared with the treated 3D-CRT plans. The D2cm improved with VMAT in
      11 of 14 cases. The 3 that worsened were still within the acceptance criteria. Of
      the 14 3D-CRT plans, 7 had a D2cm minor deviation, while only one of the 14 VMAT
      plans had a D2cm minor deviation. The R50% improved in 13 of the 14 VMAT cases.
      The 1 case that worsened was still within the acceptance criteria of the RTOG
      protocol. Of the 14 3D-CRT plans, 7 had an R50% deviation. Only 1 of the 14 VMAT
      plans had an R50% deviation, but it was still improved compared to the 3D-CRT
      plan. CONCLUSIONS: In this cohort of patients, no dosimetric compromises resulted
      from planning SBRT treatments with VMAT relative to the 3D-CRT treatment plans
      actually used in their treatment.

PMID- 28517537
TI  - SU-F-BRCD-01: A Novel Dual Source Array Tetrahedron Beam Computed Tomography
      (TBCT) System for Image Guided Radiotherapy.
AB  - PURPOSE: To design and test the feasibility of a novel dual source array, dual
      detector array TBCT system which is capable of both volumetric CT imaging as well
      as real-time stereoscopic x-ray imaging for image guided radiotherapy (IGRT).
      METHODS: Besides producing improved image quality, the geometry of TBCT is also
      more compact and flexible. It is possible to mount two x-ray source arrays and
      two detector arrays on a LINAC gantry. Each pair of source/detector arrays
      generates real-time fluoroscopy images at four different view angles, which can
      be used in real-time target/marker tracking. FDK and iterative CT image
      reconstruction algorithms were developed for this new geometry. Stereoscopic
      imaging was simulated using CT images of prostate patients with implanted
      radiopaque markers. RESULTS: Although the cone angles to the central slice of the
      reconstructed image are nonzero due to the shifting of the detector arrays,
      reconstructed patient CT images are visually identical to the original fan beam
      images. Anatomical structures and implanted radiopaque markers are visible in at
      least two of the radiography images. The 3-D spatial coordinates of the implanted
      markers can be determined from the stereoscopic images. CONCLUSIONS: TBCT with
      dual source and dual detector arrays can produce high quality CT images as well
      as real-time stereoscopic imaging for target tracking. High quality online CT
      images and stereoscopic imaging in MV beam-eye-view direction can be very useful
      for advanced treatment techniques. Tiezhi Zhang and Joshua Kim have financial
      interest in TetraImaging Inc.

PMID- 28517538
TI  - SU-E-T-641: Flattening Filter Free Dynamic Conformal Arcs for Lung Radiotherapy.
AB  - PURPOSE: To investigate the use of dynamic conformal arcs (DCA) with the
      flattening filter free (FFF) beams for lung stereotactic body radiotherapy (SBRT)
      on the TrueBeam STx (Varian, Inc., Palo Alto, CA). METHODS: Eight SBRT patients
      receiving 10-18 Gy per fraction were planned in Eclipse 10 (Varian Medical
      Systems, Palo Alto, CA) for the TrueBeam STx using DCA's with 6 MV FFF beams. The
      isocenter was placed such that the point fell near midline on each patient
      allowing full arc rotation without patient collision.Several planning methods
      were employed depending on the location of the tumor. For peripheral tumors a
      single arc was used. For peripheral tumors with chestwall interference,
      additional oblique fields were used to help pull dose off of the chestwall. For
      tumors located in the central region or close to the spine, multiple DCA's were
      used. One standard open DCA was used to deliver the majority of the dose, then
      one or two additional DCA's with organs blocked automatically using the'Fit and
      Shield' feature of Eclipse were used to help shape the dose. The arcs were then
      weighted to create the desired dose distribution. RESULTS: Beam on times for the
      8 patients averaged 2.00 minutes with a minimum time of 1.22 minutes and a
      maximum time of 3.3 minutes total. With multiple arcs or additional static
      fields, treatment time is lengthened by the time it takes to mode up between arcs
      (~1 minute) and/or move between fields. The PTV coverage of the 100% isodose line
      was >= 95% in all cases. The conformality index ranged 1.12 - 4.5, with an
      average of 2.5. CONCLUSIONS: FFF DCA is a fast, efficient way to plan and
      delivery SBRT treatments. The short treatment times directly lead to reduced
      patient motion and discomfort, which may yield improved targeting and outcomes.

PMID- 28517539
TI  - SU-F-BRCD-03: Dose Calculation of Electron Therapy Using Improved Lateral Buildup
      Ratio Method.
AB  - PURPOSE: To calculate the percentage depth dose of any irregular shape electron
      beam using modified lateral build-up-ratio method. METHOD AND MATERIALS:
      Percentage depth dose (PDD) curves were measured using 6, 9, 12, and 15MeV
      electron beam energies for applicator cone sizes of 6*6, 10*10, 14*14, and
      14*14cm2 . Circular cutouts for each cone were prepared from 2.0cm diameter to
      the maximum possible size for each cone. In addition, three irregular cutouts
      were prepared. The scanning was done using a water tank and two diodes - one for
      the signal and the other a stationary reference outside the tank. The water
      surface was determined by scanning the signal diode slowly from water to air and
      by noting the sharp change of the percentage depth dose curve at the water/air
      interface. RESULTS: The lateral build-up-ratio (LBR) for each circular cutout was
      calculated from the measured PDD curve using the open field of the 14*14 cm2 cone
      as the reference field. Using the LBR values and the radius of the circular
      cutouts, the corresponding lateral spread parameter (sigma) of the electron
      shower was calculated. Unlike the commonly accepted assumption that sigma is
      independent of cutout size, it is shown that the sigma value increases linearly
      with circular cutout size. Using this characteristic of sigma, the PDD curves of
      irregularly shaped cutouts were calculated. Finally, the calculated PDD curves
      were compared with measured PDD curves. CONCLUSIONS: In this research, it is
      shown that sigma increases with cutout size. For radius of circular cutout sizes
      up to the equilibrium range of the electron beam, the increase of sigma with the
      cutout size is linear. The percentage difference of the calculated PDD from the
      measured PDD for irregularly shaped cutouts was under 1.0%. Similar Result was
      obtained for four electron beam energies (6, 9, 12, and 15MeV).

PMID- 28517540
TI  - SU-E-T-622: A Rapid Hybrid VMAT-IMRT Planning Method Using an Abbreviated Beam
      Angle Optimization Search.
AB  - PURPOSE: To generate hybrid VMAT-IMRT treatment plans by utilizing an IMRT beam
      angle-optimality (BAO) search under a commercially available TPS without the aid
      of custom optimization software or high performance computing. METHODS: The high
      dose modulation provided by IMRT beams can be exploited to improve the quality of
      VMAT treatments. To achieve this, a VMAT treatment was created where the gantry
      pauses at predetermined angles to deliver IMRT segments. To determine IMRT BAO,
      an IMRT plan ('poly-IMRT') was made with many beams (>30) equally spaced around
      the patient. For practical reasons and to reduce the total time to approximately
      1 hour, BAO was approximated by removing one beam out of the set and noting the
      new objective score. Determining this'score penalty' for each of the beams serves
      as a proxy for true BAO. The hybrid plan was created by combining the VMAT arc
      with a user-determined number of top-ranked beams from the poly-IMRT set. The BAO
      from this approach was compared with a more rigorous method ('VMAT+1'), in which
      a VMAT plan was optimized with 1 IMRT beam at various angles, allowing a direct
      determination of objective score versus gantry angle. The overall hybrid planning
      process was demonstrated by creating separate plans for a SBRT lung patient, with
      dose normalized to the limiting maximum aorta dose. RESULTS: Large score
      penalties from poly-IMRT coincided with large score benefits from VMAT+1,
      indicating both methods identified the same optimal beams. The VMAT, IMRT, and
      hybrid plans delivered the prescription dose to 84.3%, 85.6% and 87.7% of the PTV
      and had homogeneity indices of 1.38, 1.41, and 1.32 respectively. Normal tissue
      doses were within 0.5%. CONCLUSION: The presented method can create hybrid VMAT
      IMRT plans which combine delivery efficiency with improved target coverage. The
      planning process takes about an hour using a standard TPS.

PMID- 28517541
TI  - MO-A-211-01: Volumetric Modulated Arc Therapy.
AB  - : Volumetric Modulated Arc Therapy (VMAT) is a rotational approach to the
      delivery of intensity modulated radiation therapy (IMRT) that can be delivered on
      a conventional linear accelerator. VMAT combines the dosimetric advantages of
      rotational delivery with the dose painting capabilities of IMRT. In recent years,
      VMAT has become a widely adopted clinical tool due to the conformal nature of the
      dose distributions and the efficiency of VMAT delivery. In this session, we will
      provide an overview of the VMAT delivery technique and will describe recommended
      steps for starting a VMAT program including VMAT commissioning. We will discuss
      tips and tricks for the use of VMAT for key clinical sites such as head-and-neck
      and prostate. Additionally, we will detail the role of VMAT for stereotactic
      radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). More advanced
      VMAT topics will also be discussed such as flattening filter free VMAT, gated
      VMAT, and the use of couch rotations during VMAT delivery. LEARNING OBJECTIVES:
      1. Describe volumetric modulated arc therapy (VMAT). 2. Describe commissioning of
      a VMAT delivery system. 3. Summarize the key elements of starting a VMAT program.
      4. Review patient- and machine-specific VMAT quality assurance. 5. Survey VMAT
      treatment planning systems and planning techniques. 6. Describe advanced VMAT
      techniques such as gated VMAT and flattening filter free VMAT. CONFLICT OF
      INTEREST: Richard Popple has a sponsored research agreement with Varian. David
      Shepard has a sponsored research agreement with Elekta.

PMID- 28517542
TI  - SU-E-T-634: Convex Direct Aperture Optimization for Sliding Window IMRT.
AB  - PURPOSE: To introduce a convex Direct Aperture Optimization (DAO) technique for
      sliding window IMRT. This method combines the accuracy of aperture-based dose
      calculations, which include leaf end effect, scatter, and leakage, with the
      convexity, and hence efficient solvability, of classic two phase IMRT
      optimization (fluence map optimization followed by sliding window leaf
      sequencing). METHODS: Artificial pencil beam profiles used in fluence map
      optimization are replaced with sigmoid-like profiles representing the dose
      "blocked" by a leaf while at some incremental position, per MU. More precisely,
      the profiles represent the dose from photons blocked minus that from photons
      leaked through or scattered by the leaf. These profiles can be computed by any
      clinically validated IMRT dose engine, and the scatter component for an
      individual leaf can be accurately included to the extent that it is independent
      of positions of other leaves. Variables of the resulting convex optimization are
      the MUs delivered while each leaf is at each incremental position. All
      constraints necessary to ensure a deliverable sliding window solution, such as
      those preventing leaf collision, are linear. Thus, provided the dose objective
      functions are convex, the entire IMRT optimization is convex, and therefore can
      be efficiently solved to provable optimality. RESULTS: Our derivations prove that
      DAO is convex for sliding window IMRT, and we demonstrate the technique on a
      clinical prostate case. CONCLUSIONS: By moving from the standard idealized
      fluence beamlet approach to a'fluence blocked by a leaf at position x' approach,
      we fully convexify the sliding window IMRT optimization problem, and thus avoid
      the dose degradation observed in two-step IMRT optimization and the non-convexity
      of the traditionally posed DAO problem.

PMID- 28517544
TI  - SU-E-T-645: Treatment of Multiple Brain Metastases Using Stereotactic
      Radiosurgery with Single-Isocenter Volumetric Modulated Arc Therapy: Comparison
      with Conventional Dynamic Conformal Arc and Static Beam Stereotactic
      Radiosurgery.
AB  - PURPOSE: To investigate the treatment of multiple brain metastases using
      stereotactic radiosurgery with single-isocenter volumetric modulated arc therapy
      (VMAT) compared with conventional multi-isocenter dynamic conformal arc therapy
      (DCAT) and three-dimensional conformal radiation therapy (3D-CRT). METHODS:
      Seventeen patients with 2 to 5 brain metastatic lesions were studied. The number
      of patients with 5, 4, 3, and 2 lesions were 4, 5, 4, and 4, respectively. For
      patients treated with DCAT/3D-CRT plans, VMAT plans were retrospectively
      generated, and vice versa. Single-isocenter set up was employed in VMAT plans
      while the number of isocenters was proportional to the number of lesions in
      DCAT/3D-CRT plans. The DCAT/3D-CRT and VMAT plans were generated using iPlan(r)
      RT Dose Version 4.1.1 (BrainLAB, Germany) and EclipseTM Version 8.6 (Varian, USA)
      treatment planning system, respectively. All plans were designed to be delivered
      on Novalis TxTM system (Varian, USA and BrainLAB, Germany), in which the
      accelerator equipped with a high definition multileaf collimator (HDMLC).
      RESULTS: Conformity index for VMAT plans were equivalent to or better than that
      for DCAT/3D-CRT plans. While VMAT and DCAT/3D-CRT plans were similar in target
      coverage, quality of coverage for VMAT plans was better. However, the volume
      receiving 5Gy was 46% larger for VMAT plans. In addition, the distance from
      individual lesion to the VMAT isocenter has no impact on VMAT plans. Compared
      with DCAT/3D-CRT plans, the mean monitor units (MU) decreased by 42% and the
      estimated treatment time decreased by 49% for VMAT plans. CONCLUSIONS: This work
      suggests that single-isocenter VMAT is promising for stereotactic radiosurgery in
      the treatment of multiple brain metastases. Single-isocenter VMAT is able to
      achieve comparable conformity, target coverage and quality of coverage with
      significantly superior delivery efficiency.

PMID- 28517545
TI  - SU-F-BRCD-07: Experimental Validation of Fluence Field Modulation for Noise and
      Dose Management in CT.
AB  - PURPOSE: Dose management in CT is a growing concern as the number of CT scans per
      capita rises. Fluence field modulated computed tomography (FFMCT) is a proposed
      approach for more optimal dose management, where the incident fluence pattern can
      change independently for each projection in order to minimize dose while meeting
      prescribed image quality metrics. This work studies the application of FFMCT for
      dose and noise management to a small cylindrical phantom. METHODS: Experiments
      were carried out on an experimental CT system using a small cylindrical phantom
      comprised of acrylic spheres, water and teflon rods as the object of interest.
      Modulation of the incident fluence was optimized using a simulated annealing
      algorithm that attempts to achieve user-prescribed, regionally varying SNR
      criteria while limiting dose. The modulated projections were synthesized from
      projection sets taken at various tube current settings. SNR patterns and
      predicted dose outcomes were compared to the prescribed values as well as against
      expected results using a bowtie filter. RESULTS: FFMCT resulted in SNR outcomes
      with greater agreement to the prescribed regionally varying SNR criteria than
      achieved by the bowtie filter. Dose reductions were observed for the majority of
      the object, and reached as high as 60%. Limited regions, coinciding with lower
      noise, observed dose increases less than 20%. Integral dose reduction over the
      entire object was greater than 40% when compared to a bowtie filter with
      comparable image quality in the region of interest. CONCLUSIONS: The results
      support the hypothesis that FFMCT has the potential to meet user-prescribed,
      regionally varying image quality objectives, while decreasing radiation dose to
      the patient. These results suggest that given a suitable collimator approach,
      fluence field modulated computed tomography could reap significant benefits in
      terms of reducing dose and optimizing image quality. NSERC.

PMID- 28517546
TI  - SU-E-T-626: Individualized Trade-Off of Dose Coverage and Sparing in IMRT
      Planning.
AB  - PURPOSE: We present an evidence-based approach to quantifying the dose sparing
      trade-offs between different Organs-at-risk (OARs) and the trade-off between OAR
      dose sparing and target dose coverage in IMRT plans. METHODS: The interaction
      between dose sparing of different OARs and between target dose coverage and OAR
      dose sparing are modeled using high-quality prior IMRT plans of prostate, head
      and-neck (HN), and spine SBRT cases. The dose sparing for each OAR is modeled
      separately at first based on their own anatomical features and then the
      contributions from other OARs or PTV are added into the model to account for the
      possible trade-off effects in plans whose modeled OAR DVH deviates from that of
      actual plans. RESULTS: The most significant OAR dose sparing trade-off is between
      bladder and rectum in prostate plans and between the left and the right parotids
      in HN plans. Trade-off is most apparent when the parotid on one side has very
      large overlap with the PTV. In most of these plans (83%), the planer chooses to
      loosen the dose constraint for that parotid in exchange for lower contra-lateral
      parotid median dose. The interaction between OAR dose sparing and PTV dose
      coverage is most significant in spine SBRT plans, (R2=0.37). Another important
      factor is the tightness of the geometric enclosure of PTV around OAR (R2=0.38).
      CONCLUSIONS: The dosimetric trade-off between multiple OARs and between PTV and
      OAR in IMRT planning is quantified by studying prior plans. These findings will
      help physicians and planners obtain better OAR dose sparing by exploring
      different trade-off options for individual patient cases. Partially supported by
      a master research agreement with Varian Medical Systems, Inc.

PMID- 28517543
TI  - MO-A-213AB-11: First Experimental Test of Secondary Ion Tracking for the
      Assessment of Beam Range in a Patient-Like Phantom.
AB  - PURPOSE: Radiation therapy with ion beams provides highly conformal dose
      distributions. Therefore, monitoring the dose delivery within the patient in a
      non- invasive way is desired. The clinically available method based on tissue
      activation measurements with a PET-camera shows limitations due to the low
      induced activities and biological washout of the activated nuclei. The prompt
      production of secondary ions is supposed to be less influenced by biological
      processes. This contribution investigates the feasibility of beam range
      monitoring in a patient-like geometry containing realistic tissue
      inhomogeneities. METHODS: The experiments were performed at the Heidelberg Ion
      Beam Therapy Center in Germany using carbon ion beams of 213 and 250MeV/u. Static
      pencil beams (FWHM of 6mm) were applied to the skull base and brain regions of a
      head phantom containing real bones. The emerging secondary ions were registered
      by the silicon detector Timepix. It was developed by the Medipix Collaboration
      and provides 256*256 pixels with 55um pitch. To determine the direction of the
      particles, a multi-layered detector (3D voxel detector, J.Jakubek etal. JINST6
      C12010) was employed. The contribution of K. Gwosch etal. addresses the
      performance of this method in a homogeneous phantom. RESULTS: In the 3D
      distributions of the measured secondary ions clear differences between the
      application of lower and higher energies were observed. This Result was achieved
      in both brain (homogeneous) and skull base regions (containing inhomogeneities).
      Differences between the energies could be observed with the detector positioned
      on the occipital side as well as on the facial side of the head. CONCLUSIONS: We
      performed the first experiments towards beam range monitoring in a patient-like
      geometry exploiting tracking of prompt secondary ions with a small detector
      prototype. Despite the inherent tissue inhomogeneities, we found sensitivity on
      the beam range in both brain and skull base. Research carried out in frame of the
      Medipix Collaboration. Research carried out in frame of the Medipix
      Collaboration.

PMID- 28517547
TI  - MO-A-213AB-04: Verification of 4D Dose Delivery Using 4D Digital Human Phantom.
AB  - PURPOSE: At present, techniques of 4D dose verification in radiation therapy for
      lung cancers associated with respiratory motion are very limited, due to either
      lack of patient anatomy or breathing information. The aim of this study is to
      develop a 4D dose verification technique based on XCAT phantom which incorporates
      both patient anatomy and respiratory mechanics. MATERIALS AND METHODS: The 4D
      XCAT phantom which possesses patient specific anatomy and allows input of
      respiratory parameters was generated using an integrated Matlab program. 10-phase
      4DCT, MIP, and AIP images generated from 4D-XCAT were used for designing a 3D
      conformal treatment plan. Real-time dose delivery was simulated by calculating
      the deposited dose in each phase of 4D-XCAT for each beam with fixed individual
      planning dose. The 4D delivered dose was determined by accumulating dose
      deposition of all beams in all phases using deformable image registration
      implemented in VelocityAl software. The planned and delivered doses were compared
      based on target coverage and DVHs of OARs (lungs, cord, heart, and esophagus).
      RESULTS: Target volume coverage was 97.5% in the simulated real-time delivery, as
      compared to 95% as planned based on AIP. Maximum cord dose, maximum esophagus
      dose, mean heart dose, and V20Gy of lung were comparable between the planned and
      delivered dose; the relative difference were 0.3%, 4.0%, 0%, and 2.8%,
      respectively. These results indicates AIP-based planning was a close
      representation of the real 4D dose delivery for both target and OARs when the
      breathing pattern is regular and reproducible. CONCLUSION: A framework has been
      successfully established for verifying 4D dose delivery using the 4D-XCAT phantom
      and deformable image registration. This verification method is capable of
      incorporating specific patient anatomy and respiratory mechanics.

PMID- 28517548
TI  - SU-E-T-638: Treatment Margins Expansion for CyberKnife Treatment Plans.
AB  - PURPOSE: The CyberKnife uses an online prediction model to track moving targets.
      The system works well if patients can breathe regularly. However, some patients
      cannot maintain a regular breathing pattern, which means a larger PTV margin is
      necessary for these patients to ensure sufficient CTV dose coverage. However, it
      is very difficult to predict a patient's breathing pattern in advance. The
      purpose of this study is to investigate a quick and easy way to adapt the
      treatment plan if extra margins are needed. METHODS: Multiple algorithms have
      been developed to calculate the adjustment. Generally, if a larger target region
      requires coverage by the prescription dose, the size of the beams will be larger
      and they should move in a peripheral direction for a certain distance to avoid
      hot spots. Dose is recalculated and renormalized consistently after the
      adjustment. If the dose distribution of the new plan covers the new PTV with
      acceptable conformality and coverage, the plan will be used for treatment.
      Otherwise, more iterations of the adjustment are performed. Dose calculations are
      limited to a small region surrounding the target to reduce calculation time.
      RESULTS: 5 clinical cases (3 lungs, 1 liver and 1 adrenal) have been tested in
      this study. The dose margin can be extended up to 10 mm without changing dose
      distributions around the target region dramatically. The average PTV coverage is
      98.7% compared to 99.1% in the original plans and the average CI is 1.22, which
      is slightly less than the 1.24 in the original plans. CONCLUSIONS: Treatment
      margins can be sufficiently expanded resulting in satisfactory plan quality for
      patients with breathing irregularities.

PMID- 28517549
TI  - SU-E-T-649: Evaluation of RapidArc- Based Stereotactic Cranial Radiotherapy Plans
      with MU Objective Using Multiple Non Coplanar Arcs in Comparison with
      Conventional Dynamic Conformal Arc Technique.
AB  - PURPOSE: Previous researches reported that RapidArc plans for stereotactic
      cranial radiotherapy have two to three times more MUs as compared to Conventional
      Dynamic Conformal Arc (DCA) Technique. This study aims to evaluate RapidArc plans
      using multiple non- coplanar arcs, developed with MU objective constraint in the
      optimization stage. METHODS: Five single brain metastasis and three multiple
      metastases cases previously planned using DCA techniques in BrainLab iPlan
      Version 4.1 were investigated in this study. For each case, the target was
      defined on CT-MR fused images in iPlan. The CT images and contours of these
      patients were exported from iPlan to Varian Eclipse TPS Version 8.6. For each
      case, a DCA plan and a RapidArc plan with multiple non-coplanar arcs with and
      without using MU objective in the optimization stage were generated using Varian
      Trilogy machine with Millennium 120 MLC keeping the same prescription and
      critical structure dose limits. All plans were evaluated according to Conformity
      Index (CI-modified Paddick) Homogeneity Index (HI), and the normal tissue volume
      receiving various dose levels (V80%, V50%, V25% and V10%). RESULTS: In all the
      plans, the target objectives were met and dose to OARs was within tolerance dose
      constraints. RapidArc plans with and without MU objective showed better CI and HI
      as supposed to DCA plans. V80%, V50%, V25% and V10% of normal tissue for RapidArc
      plans are equal or lesser than DCA plans. Single isocentre RapidArc plan for
      closely spaced multiple metastases cases showed better dose fall off between the
      lesions as supposed to DCA plans. RapidArc plans with MU objective resulted in
      comparable MUs as that of DCA plans. CONCLUSIONS: Our study showed RapidArc plans
      done with and without MU objective have no significant dosimetric difference in
      plan objectives. Therefore, multiple non-coplanar RapidArc plans with MU
      objective is clinically feasible and can provide better treatment plans than
      conventional DCA plans, especially for complicated cases.

PMID- 28517550
TI  - SU-E-T-619: A Network-Flow Solution Approach to VMAT Treatment Plan Optimization.
AB  - PURPOSE: To add mathematical rigor to the merging phase of the recently published
      two-stage VMAT optimization method called VMERGE. Using an exact merging method,
      we are able to better characterize the tradeoff between delivery efficiency and
      dose quality. METHODS: VMERGE begins with an IMRT plan that uses 180 equi-spaced
      beams and yields the "ideal" dose. Neighboring fluence maps are successively
      merged, meaning they are added together and delivered as one map. The merging
      process improves the delivery time at the expense of deviating from the initial
      high-quality dose distribution. We replace the original heuristic merging method
      by considering the merging problem as a bi-criteria optimization problem:
      maximize treatment efficiency and minimize the deviation from the ideal dose. We
      formulate this using a network-flow model where nodes represent the beam angles
      along with the starting MLC leaf position and arcs represent the possible merges.
      Since the problem is non-convex, we employ a customized box algorithm to obtain
      the Pareto approximation. We also evaluate the performance of several simple
      heuristics. RESULTS: We test our exact and heuristic solution approaches on a
      pancreas and a prostate case. For both cases, the shape of the Pareto frontier
      suggests that starting from a high quality plan, we can obtain efficient VMAT
      plans through merging neighboring arcs without substantially deviating from the
      initial dose distribution. The trade-off curves obtained by the various
      heuristics are contrasted and shown to all be equally capable of initial plan
      simplifications, but to deviate in quality for more drastic efficiency
      improvements. CONCLUSIONS: This work presents a bi-criteria network-flow solution
      approach to the merging problem. The obtained Pareto-frontier approximation is
      used as a benchmark to evaluate the performance of the proposed merging
      heuristics. The results validate that one of the heuristics in particular can
      achieve high-quality solutions.

PMID- 28517551
TI  - MO-A-BRCD-01: Unsettled Issues in the Radiobiology of Emergent Technology:
      Hypofractionation and PET-Guided Treatment Planning.
AB  - : New technologies and innovative treatment techniques call into question long
      standing radiobiological principles in RT. Reported apoptosis effects above 10
      Gy/fraction challenge standard views of tumor cell kill as the only important
      path to tumor control. There are also reports of an immune-system response to
      large-dose per fraction. Repair-kinetics can also become important when comparing
      treatments given in less than 10 minutes to treatments given over 30 minutes or
      more. Modeling studies challenge the importance of hypoxia (and use of the linear
      quadratic model) in hypofractionation treatments. Critical questions regarding
      the use of FDG-PET guided boosts include the expected dose needed to achieve
      local control for FDG-PET positive tumors, and the relationship between FDG-PET
      images and underlying cellular parameters. This symposium will review our current
      scientific understanding of these important, unsettled issues. LEARNING
      OBJECTIVES: 1. Review non-classical radiobiology relevant to high-doses per
      fraction 2. Review dose-rate effects as they apply to SBRT/hypofx treatments 3.
      Review radiobiology of FDG-PET guided therapy.

PMID- 28517552
TI  - Clinical and radiographic outcomes of immediate and delayed placement of dental
      implants in molar and premolar regions.
AB  - PURPOSE: The purpose of this retrospective study was to determine clinical and
      radiographic outcomes of immediate and delayed placement of dental implants in
      molar and premolar regions. MATERIALS AND METHODS: Clinical and radiographic
      records of 116 patients who received implants in molar and premolar regions were
      included in this study. After implantation, patients were recalled for
      assessments at 1 month, 3 months, 6 months, 1 year, and every year thereafter. In
      addition, anatomic location, type of prosthesis, gender, stage, diameter, and
      length of implants were analyzed. RESULTS: Of these 116 patients, 55 were males,
      and 61 were females. Their mean age was 50.9 years. They received 85 immediate
      implants and 147 delayed implants in molar and premolar regions. Gender, type of
      prosthesis, stage, implant diameter, and implant length were not significantly
      different between the immediate placement group and the delayed placement group,
      although anatomic locations were significantly different between the 2 groups.
      Their mean follow up time after dental implantation was 3 years (range, 6 months
      to 9 years). Kaplan-Meier survival estimates showed 97.8% probability of survival
      up to 9 years in the delayed placement group and 100% probability of survival up
      to 8 years in the immediate placement group. There was no significant difference
      in implant survival according to the time of implantation. No significant
      difference in cervical bone loss (CBL) at the mesial or distal side was found
      between the 2 groups. CBL according to anatomic location, the type of prosthesis,
      or gender was not significantly different either between the 2 groups. However,
      CBL at distal side of 1-stage approach was significantly (P < .05) smaller in the
      delayed placement group than that in the immediate placement group. CONCLUSION:
      This study showed that immediate dental implantation in molar and premolar
      regions had good clinical and radiographic outcomes.

PMID- 28517554
TI  - SU-E-J-08: Dependence of Imaging Dose on Image Quality of Free-Breathing 3DCBCT
      of Moving Tumors.
AB  - PURPOSE: To evaluate the impact on free-breathing CBCT (FBCBCT) image quality to
      properly visualize the motion range of moving tumors as a function of imaging
      dose. METHODS: A multi-purpose body phantom (QUASAR) with a cylindrical cedar
      wood (density = 0.330g/cc), and an embedded 3-cm diameter Polystyrene sphere
      (density = 0.855g/cc) were used to simulate lung tumor motion. Varian Trilogy
      with OBI system was used to acquire CBCT images (high-dose mode: 125kVp, 80mA,
      25ms/frame & low-dose mode: 110kVp, 20mA, 20ms/frame). As the FBCBCT projections
      were acquired, the sphere moved in accordance to 30 simulated sinusoidal patient
      breathing patterns using a programmable motion platform, which were given the
      parameters: inhalation-to-exhalation (I/E) ratio ranging from 1-0.2131,
      amplitudes of 1 and 3 cm, and periods 2, 4, and 6 seconds. Following the
      acquisition of FBCBCT images, the ITV contrast, defined as = (target pixel values
      inside the sphere - avg. pixel values in background)/(avg. pixel values in
      background), were calculated per image slice. RESULTS: All parameters, I/E ratio,
      period, and amplitude did not seem to have much impact on the percentage change
      of the ITV contrast as a function of imaging dose. The percentage-change for all
      coronal images with a reduced ITV contrast when going from high-dose to low-dose
      was - 4.61 +/- 3.04%, while the percentage-change for all coronal images with an
      ncreased ITV contrast when going from high-dose to low-dose, was 8.19 +/- 3.61%.
      The overall percentage-change of all 30 coronal images was 5.21 +/- 6.49%.
      CONCLUSIONS: We found that imaging dose did not have much impact on the
      visibility of the ITV volume, irrespective of the amplitude, I/E ratio, or
      period. Thus, it seems that low-dose FBCBCT may be just as suitable for clinical
      use while sparing a significant imaging dose to the patients.

PMID- 28517553
TI  - IFI16 reduced expression is correlated with unfavorable outcome in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Its
      clinical course is typically indolent; however, based on a series of
      pathobiological, clinical, genetic, and phenotypic parameters, patient survival
      varies from less than 5 to more than 20 years. In this paper, we show for the
      first time that the expression of the interferon-inducible DNA sensor IFI16, a
      member of the PYHIN protein family involved in proliferation inhibition and
      apoptosis regulation, is associated with the clinical outcome in CLL. We studied
      99 CLLs cases by immunohistochemistry and 10 CLLs cases by gene expression
      profiling. We found quite variable degrees of IFI16 expression among CLLs cases.
      Noteworthy, we observed that a reduced IFI16 expression was associated with a
      very poor survival, but only in cases with ZAP70/CD38 expression. Furthermore, we
      found that IFI16 expression was associated with a specific gene expression
      signature. As IFI16 can be easily detected by immunohistochemistry or flow
      cytometry, it may become a part of phenotypic screening in CLL patients if its
      prognostic role is confirmed in independent series.

PMID- 28517555
TI  - SU-E-J-45: Validation of the ExacTrac Virtual Isocenter Based Target Localization
      Method.
AB  - PURPOSE: With no stable landmarks available for localization, a 'virtual
      isocenter' "'or surrogate landmark near the target'" can be used for image
      guidance. However, using a virtual isocenter in ExacTrac has not been thoroughly
      validated. This study evaluates its target localization accuracy and investigates
      the impact of two different couch correction sequences. METHODS: A CT scan was
      acquired on an anthropomorphic thoracic phantom with a 2mm-diameter ball bearing
      (BB) marker implanted in thelung region. A treatment plan was created with
      isocenter placed at the BB center, and exported to ExacTrac. In ExacTrac, a
      virtual isocenter wasplaced on a spine vertebral body where three translational
      shifts (8.8cm laterally, 1.5cm longitudinally and 6cm vertically) were present. A
      series ofcouch rotations (+/-3 degrees, 1 degree increment) was intentionally
      applied to simulate angular setup variations. For each rotation, two stereoscopic
      x-rayimages were acquired and fused using the ExacTrac 6D registrationalgorithm.
      Calculated shifts were applied using two sequences: (1)automatic 5D corrections
      (three translations/two robotic couch rotations) followed by manual couch
      rotation; (2) manual couch rotation then automatic 5D corrections. After each
      ExacTrac localization, orthogonal (anterior-posterior and right-lateral) portal
      images were acquired to quantify BB center deviations from the radiation
      isocenter as an indicator of residual error. RESULTS: Minimal difference between
      investigated table correction sequences was observed. Average translational
      deviations between the BB and radiation isocenter (mean+/-1SD) were 0.3+/-0.3mm
      and 1.0+/-0.2mm for lateral and vertical axis respectively. Longitudinally, the
      deviations were 0.8+/-0.4mm from the anterior-posterior image and 0.1+/-0.3mm
      from the right-lateral image. The systematic difference (0.7+/-0.1 mm) between
      thetwo may have been attributed to gantry sagging during rotation. CONCLUSIONS:
      ExacTrac system successfully corrected angular shifts using the virtual isocenter
      method in a rigid phantom setup. The sequence ofcouch correction did not
      influence the localization accuracy. Further patient study is warranted.

PMID- 28517556
TI  - SU-E-J-18: Evaluation of the Effectiveness of Compression Methods in SBRT for
      Lung.
AB  - PURPOSE: This study aims to evaluate the effectiveness of compression in
      immobilizing tumor during stereotactic body radiotherapy (SBRT) for lung cancer.
      METHODS: Published data have demonstrated bigger respiratory motion in lower lobe
      than in upper lobe during normal breathing. We hypothesize that 4DCT-based
      patient selection and abdominal compression would immobilize lung tumor volumes
      effectively, regardless of their location. We retrospectively reviewed 12 SBRT
      lung cases treated with Trilogy(r) (Varian Medical System, Palo Alto, CA). Either
      compression plate or Vac-LokTM was used as abdomen compression of the SBRT
      immobilization system (Body Pro-LokTM, CIVCO) to restrict patients' breathing
      during CT simulation and treatment delivery. These cases are grouped into 2
      categories: lower and upper lobe tumor, each with 6 cases. Records for 33
      treatments were studied. On each treatment day, the patient was set up to the
      bony anatomy using kV-kV-match. A CBCT was performed to further set up the
      patient to the tumor based on the soft tissue information. The shifts from CBCT
      setup were analyzed as displacement vectors demonstrating the magnitude of the
      tumor motion relative to the bony anatomy. RESULTS: The mean magnitude of
      displacement vectors for upper lobe and lower lobe were 3.7+/-2.7 and 4.2+/-6.3,
      [1S.D.] mm, respectively. The Wilcoxon rank sum test indicates that the
      difference in the displacement vector between the two groups is not statistically
      significant (p-value = 0.33). CONCLUSIONS: The magnitude of shifts from CBCT were
      small with mean value <5mm in SBRT lung treatments. No statistically significant
      difference were observed in the displacement of tumor between lower and upper
      lobes. With limited sample size, this suggests that our current 4DCT
      screening/abdominal compression approach is effective in restricting the
      respiration-induced tumor motion despite its location within the lung. We plan to
      confirm this Result in additional patients.

PMID- 28517557
TI  - SU-E-J-56: Localization Error in Gamma Radiosurgery with 3T MR Due to Fiducial
      Box Chemical Shift from Incorrect Liquid Filling Materials.
AB  - PURPOSE: Use of a 3D MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by
      Copper) polymer gel dosimeter to evaluate potential localization and positioning
      errors due to the use of incorrect liquid filling material (baby oil instead of
      copper sulfate) for a gamma radiosurgery (GSR) MRI fiducial box. METHOD AND
      MATERIALS: Two phantoms were used to evaluate geometric errors due to chemical
      shift for 'baby oil' fiducial markers: 1) a cylindrical grid phantom with Teflon
      rod insert; 2) a human skull phantom with a MAGIC (Gelatin 9%; Methacrylic acid
      4%; CuSO4 0.1mM; Ascorbic acid 2mM; Glucose 10%) gel capsule to simulate an
      intracranial target. Both phantoms were stereotactically MR and CT scanned for
      GSR treatment planning using a 'baby oil' GSR MRI fiducial box and a standard CT
      fiducial box. The gel capsule was given 15Gy @ 50% isodose line using the
      4mmcollimator based on 'baby oil' fiducial box MR images. Then, the skull phantom
      with capsule was scanned in 3T GE Signa(r) EXCITETM clinical scanner (Spin Echo
      pulse sequence) for 3D dose distribution read-out. Dose distribution errors were
      analyzed based on gel results for the combined MR and CT plans. For comparison,
      deviation of grid phantom teflon rods were directly measured from MR and CT
      stereotactic images. RESULTS: Gel dose profile measurements indicate a 3.8mm
      shift in the phase encoding direction for the 'baby oil' fiducial marker for 3T
      MRI based GSR treatment planning. A 3.7mm shift in Teflon rod position was also
      confirmed through direct comparison of CT and MR images. CONCLUSION: Both results
      showsignificant target localization and positioning errors can be caused if
      inappropriate filling materials are used for GSR MRI fiducial boxes. Thisstudy
      also indicates that MAGIC polymer gel can be used as a versatile toolfor GSR 3D
      quality assurance.

PMID- 28517558
TI  - SU-E-J-29: Evaluation of Effectiveness of Immobilization Devices for Radiation
      Therapy with Repeated CBCT Studies.
AB  - PURPOSE: To evaluate the effectiveness of three different immobilization devices
      for lung radiation therapy with daily and/or weekly cone-beam CTs (CBCT).
      METHODS: Three different immobilization devices, short (IM1) and long (Im2 ) Vac
      lok cushion with wing boards (Civco), BodyFix (Im3 , Elekta), were investigated.
      Repeated CBCT images for 3 SBRT patients immobilized with Im3 , and 6 IMRT
      patients immobilized with IM1 and Im2 (3 each) were acquired. Each SBRT patient
      received 70 Gy in 10 fractions and setup daily with CBCT, while IM1 and Im2
      patients were setup daily with orthogonal kV, and weekly CBCT (week 0-6). The day
      1, 6 and 10 CBCT for Im3 were considered week 0-2 CBCT. Patient setup was first
      based on skins markers then shifts were made based on bony landmarks in kV and
      GTV with CBCT. Skin contours, which are further away from the isocenter and thus
      more sensitive to rotation and skin folding, were extracted in each CBCT data set
      and the difference on skin contours were investigated for both before and after
      shifts. RESULTS: Over 2 weeks of treatment, Im3 has the smallest standard
      deviation for setup shifts (0.09, 0.16, 0.20 cm on LR, UD and IO directions)
      compared to IM1 (0.29, 0.35, 0.34 cm) and Im2 (0.11, 0.19, 0.40 cm), which
      indicates setup based on skin markers were the most reproducible for Im3 . Over 6
      weeks of treatment, Im2 (0.16, 0.18, 0.42 cm) is more reproducible than IM1
      (0.44, 0.45, 0.35 cm). All 3 patients with IM1 and 2 patients with Im2 were found
      to have >1 cm difference in skin contour even after shifts were made. 1 patient
      with IM1 was found to have non-reproducing skin folding of >3 cm difference.
      CONCLUSIONS: Information derived from repeated CT images could be used to
      evaluate the effectiveness of the immobilization devices.

PMID- 28517559
TI  - SU-E-J-38: Rotational Setup Errors in Pediatric Patients Receiving Radiation
      Therapy for Intracranial Tumors.
AB  - PURPOSE: We have clinically observed that larger rotational setup errors are more
      prominent in pediatric patients who received radiation therapy for brain tumors.
      In this work, we quantitatively evaluated the daily setup corrections in pitch,
      roll, and yaw axes for children who received intracranial radiation therapy under
      x-ray image guidance. METHODS: Daily localization data of 43 patients between the
      ages of 10 months and 21.9 years were analyzed in this study. Patients were
      immobilized with thermoplastic mask during treatments, and 2D orthogonal x-ray
      images wereacquired for setup corrections before each treatment. Rotational setup
      corrections in pitch, roll, and yaw axes were extracted from 873 treatment
      fractions, and were analyzed for the whole group of patients and for two age
      groups: < 5 and = 5 years old. RESULTS: The mean values for the pitch corrections
      were 1.91 degrees  and 1.65 degrees  (p:0.02), roll corrections were 1.37 degrees
      and 1 degrees  (p<0.001), and yaw corrections were 1.93 degrees  and 1.47
      degrees  (p<0.001), respectively. For patients < 5 years, 21.7% of treatments had
      pitch corrections more than 3 degrees , versus 15.6% of treatments required pitch
      corrections more than 3 degrees  for patients >= 5 years. Similarly, 10.6% of
      roll corrections and 20.9% of yaw corrections were more than 3 degrees  for
      patients < 5 years. On the other hand, 2.1% of roll and 13.8% of yaw corrections
      were more than 3 degrees  for patients = 5 years old. CONCLUSIONS: Data indicate
      that children less than 5 years old are more prone to rotational setup errors
      during intracranial radiation therapy. This can be attributed to reduced efficacy
      of immobilization devices due to smaller and rounder anatomicalfeatures of
      pediatric patients, and challenges in setup while the patient is under
      anesthesia. The role of daily image guidance and rotational setup corrections
      becomes important to ensure target coverage, especially for children < 5 years
      old.

PMID- 28517560
TI  - SU-E-J-11: Characterization of Interfractioanal Anatomical Variations in Post
      Operative Radiation Therapy for Prostate Bed.
AB  - PURPOSE: To quantitatively characterize the interfractional anatomic variations
      in post-operative radiation therapy (RT) for prostate bed, so that appropriate
      strategy that can fully address these variations can be developed. METHODS: A
      total of 102 daily pre-treatment CT acquired using an in-room CT (CTVision,
      Siemens) for 10 patients treated with post-operative IG-IMRT of prostate bed.
      Prior to each fraction, patients were repositioned to correct for interfractional
      translational shifts based on the alignment of both anterior rectal wall and
      surgical clips between the daily CT and the planning CT. The PTV was assumed to
      be the volume enclosed by the 95% prescription isodose surface generated for the
      conventional four field box. Contours of the PTV, rectum and bladder on each
      daily CT were generated by populating the planning contours using an auto
      segmentation tool based on deformable registration (ABAS, Elekta) with manual
      editing. Interfrcational variations in the volumes, shapes and positions of these
      contours were obtained. The displacement of the center of mass (DCOM) with
      respect to the isocenter was used to measure interfractional organ motion, and
      the maximum overlap rate (MOR) was used to measure organ deformation. RESULTS:
      Interfractional variations in the volumes of rectum and bladder were in the range
      of 50-270% (average 116+/-41%) and 30-180% (average 67+/-26%), respectively. The
      averages of DCOM for rectum are: - 0.35+/-0.46cm (lateral, varying from -1.58 to
      1.23cm), -0.33+/-0.99cm (longitudinal, varying from -2.4 to 1.8cm), and -3.41+/
      1.14cm (vertical, varying from -5.56 to -0.99cm). These values for bladder are: 
      0.20+/-0.50cm (lateral, varying from -1.48 to 0.61cm), 3.63+/-1.10cm
      (longitudinal, varying from -5.7 to 3.1cm), and -0.31+/-0.97cm (vertical, varying
      from -1.68 to 2.77cm). CONCLUSIONS: Large interfractional changes in organ
      volumes, shapes and positions are seen in post-operative RT for prostate bed.
      These changes cannot be accounted for by the current standard practice of IGRT
      repositioning. This work is supported partially by MCW Cancer Center Fotsch
      Foundation.

PMID- 28517561
TI  - SU-E-J-49: Reliability Study of ExacTrac- System Image Isocenter Using an On
      Demand QA Procedure.
AB  - PURPOSE: To develop a pointer based quality assurance (QA) procedure that quickly
      verifies the congruence of ExacTrac(r) image isocenter with the radiation
      isocenter of a linear accelerator (linac), and use it to study the accuracy and
      reliability of the ExacTrac(r) image isocenter. METHOD AND MATERIALS: A 6 mm
      diameter tungsten ball was aligned with the room laserusing a pointer alignment
      system. By measuring the positions of ExacTrac(r)image isocenter and linac
      radiation isocenter relative to the ball, thedeviations between the two
      isocenters was easily calculated. The ExacTrac(r)image isocenter relative to the
      ball was measured using the built-in Winston-Lutz Pointer test, in which kV
      images of the ball are projected to flat panels and the center of the ball to the
      image isocenter are calculated by ExacTrac(r) software. The linac radiation
      isocenter relative to the ball was measured by taking the portal images of the
      ball at four gantry angles, 0,90, 180 and 270 with a 6 * 6 cm2 field. An in-house
      developed software was used to identify the center of the ball and the center of
      the radiation. This procedure was used in weekly QA for a year in this work.
      RESULTS: A simple QA procedure was developed to ensure the accuracy of
      ExacTrac(r) imageisocenter against the linac radiation isocenter. The procedure
      can be executed in less than 20 minutes. The data show the position error were -
      0.27+/-0.30, 0.52+/-0.24, 0.18+/-0.22 mm in the lateral, vertical and
      longitudinal directions, and the max deviation were 0.86, 0.89 and 0.54 mm
      respectively. CONCLUSION: The weekly verification data showed the ExacTrac(r)
      image isocenter can be very reliable with sub-millimeter accuracy. This level of
      imaging alignment accuracy is necessary for imaging guided SBRT procedures. The
      quick QA procedure can be applied on-demand to ensure the accuracy of ExacTrac(r)
      isocenter.

PMID- 28517562
TI  - SU-E-J-22: Effect of MLC Leaf Width on MLC Leaf Shifting Algorithm for Concurrent
      Treatment of Prostate and Pelvic Lymph Nodes.
AB  - PURPOSE: Our previous study showed that adjusting selected MLC leaf pairsto
      follow prostate movement is an effective strategy to account for daily prostate
      displacement during concurrent treatment with pelvic lymph nodes. MLC leaf width
      affects the quality of MLC shifting plans for longitudinal prostate motion
      compensation. This study is to investigate the effect of the MLC leaf width in
      compensation of the prostate movement. METHODS: Fifty-one daily CT on-rail scans
      from three patients were available for this study. On these CTs, the prostate,
      bladder and rectum were manually contoured, and the lymph nodes contours were
      transferred from the planning CT after rigid bony registration. For each patient,
      three different IMRT plans were created based on a planning CT using leaf width
      of 2.5, 5, and 10 mm, respectively. For each CT, the prostate displacement was
      determined by dual imaging registration and compensated by shifting MLC resulting
      in a total of 153 MLC shifted plans. RESULTS: Among 51 daily CTs, the average
      prostate movement along the superior/inferior direction was 1.1+/-3.7 mm (range: 
      6 to 6.5 mm). The differences in D99 of the prostate between the dose of the day
      and dose of the plan were 2.3+/-3.3%, 1.3+/-2.0%, and 4.4+/-5.1% for 2.5, 5, and
      10 mm leaf width plans, respectively (p<<0.05). The corresponding differences in
      D99 of the lymph nodes were 0.7+/-0.9%, 0.6+/-0.9%, and 1.4+/-0.8%. The mean
      differences in D50 were 0.8%, 1.6%, and 2.7% for the bladder, and 10.0%, 3.9%,
      and 5.7% for the rectum, respectively. CONCLUSIONS: Using the MLC Shifting method
      to compensate for prostate movement in the longitudinal direction depends on the
      MLC leaf width and the magnitude of the prostate motion. The use of leaf width of
      5 mm can provide sufficient tumor coverage without significantly affecting doses
      to the critical structures.

PMID- 28517563
TI  - SU-E-J-60: Comparison of CT-On-Rails and a 3D Surface Imaging System for Image
      Guided Pelvic Radiation Therapy for Both Supine and Prone Patient Positions.
AB  - PURPOSE: We investigate the feasibility of using AlignRT for pelvic radiation
      image guidance. The uniqueness of our study is that all patients have multiple CT
      on-rails (CTOR) scans to compare corresponding AlignRT images to. METHODS: Ten
      patients receiving pelvic radiation were enrolled in this study. Two simulation
      CT scans were performed in supine and prone positions for each patient. Body
      surface contours were generated in treatment planning system and exported to
      AlignRT to serve as reference images. The patient was aligned to treatment
      isocenter with room lasers, and then scanned with both CTOR and AlignRT in both
      supine and prone positions. Image guidance shifts were calculated for both
      modalities by comparison to the simulation CT and the differences between them
      were analyzed. These procedures were performed for each patient once per week for
      five weeks. The average and maximum difference of displacement between AlignRT
      and CTOR were calculated for each patient. RESULTS: For supine position, there
      are 4 patients who had the average difference of displacement between AlignRT and
      CTOR along any direction (vertical, longitudinal, and lateral) greater than
      0.5cm, and 1 patient greater than 1cm. For prone position, there are 7 patients
      who had the average difference greater than 0.5cm, and 3 patients greater than
      1cm. For supine position, there are 4 patients who had the maximum difference
      great than 1cm. For prone position, there are 9 patients who had the maximum
      difference greater than 1 cm. The difference of displacement between AlignRT and
      CTOR is greater for prone position than for supine position. CONCLUSIONS: AlignRT
      does not appear to be an advisable image guidance approach for pelvic radiation
      therapy for patients with either supine or prone position. There appears to be a
      potential for large alignment discrepancies (up to 2.25 cm) between AlignRT and
      CTOR.

PMID- 28517565
TI  - SU-E-J-05: Validation of an Iterative Tomosynthesis Algorithm for Low Dose on
      Board Cone Beam CT Patient Localization.
AB  - PURPOSE: Cone beam CT (CBCT) is a well established technique to localize patients
      using bone and soft tissue anatomy. Current protocols are limited to one weekly
      CBCT due to the considerable imaging dose delivered to the patient. The purpose
      of this project is to develop and validate a low dose CBCT algorithm to reduce
      dose and imaging time of current 3D imaging localization procedures using a novel
      iterative tomosynthesis algorithm to allow daily CBCT for patient positioning and
      target localization. METHODS: The algorithm is based on the combination of a
      tomosynthesis filtered back propagation (TFBP) acquisition geometry algorithm and
      a maximum likelihood expectation maximization (MLEM) iterative reconstruction.
      Circular or arc acquisition trajectory, projection number, and angular projection
      position are optimized according to the anatomical treatment site and region of
      interest. The TFBP method provides the first 3D image estimate, and the MLEM
      improves its quality. In this study, we focused on head and neck treatment
      localization imaging. RESULTS: We studied the performance of our tomosynthesis
      algorithm imaging resolution on an anthropomorphic head and neck phantom to
      determine image quality as a function of dose reduction techniques. Reconstructed
      anatomy shows that a 1/8 dose reduction provides similar image quality and
      resolution as current CBCT protocols. Seven iterations show an optimal compromise
      between image quality and reconstruction time. Tomosynthesis images provide
      digitally reconstructed radiographs with similar resolution and contrast as full
      CBCT. We verified that the iterative process eliminates phantom images originated
      by the acquired sparse angular data projections. CONCLUSIONS: We developed and
      validated an iterative algorithm for low dose cone beam CT based on circular or
      arc tomosynthesis geometries and iterative reconstruction techniques. The
      algorithm combines the strengths of both techniques to provide a novel low dose
      method to image patient anatomy for patient positioning and target localization.

PMID- 28517564
TI  - SU-E-J-33: Geometric Agreement Check for Imaging System with Radiation Beam by KV
      and MV-CBCT.
AB  - PURPOSE: The verification method of the geometry agreement between a light field
      and/or a laser coordinate and treatment beam should be easy and quick. In this
      presentation, we propose a novel QA method by using both kV- and MV-CBCT for kV
      IGRT system. This method confirms the temporal unchanging the agreement of
      geometry in the kV-IGRT system with the treatment beam geometry. METHODS: 1) MV
      flexmap: Sequential MV-projection images were acquired during gantry rotation by
      iViewGT (Elekta) and MV-CBCT was reconstructed by in-house software with a
      flexmap correction. The flexmap is displacement of gantry and detector panel
      related with gantry sag. The geometric change affects the deranging reconstructed
      image. To evaluate how much displacement of EPID panel and gantry was detectable,
      the images of 8mm diameter ball-bearing (BB) located at the radiation isocenter
      were reconstructed with improper Flexmap.2) A comparison between the kV-CBCT and
      the MV-CBCT: The kV-CBCT was provided by X-ray Volume image (XVI) system
      (Elekta). To confirm the agreement for the geometry between kV-IGRT system and
      treatment beam, the kV-CBCTs of BB are compared with that of MV-CBCTs. RESULTS:
      The flexmaps were modified to (b)1mm / (c)3mm shifted to the rotation direction
      and (d)3mm to the rotation axis. The MV-CBCT were reconstructed with the correct
      flexmap and with incorrect flexmap (b), (c) and (d).a??The geometric confirmation
      for MV-CBCT was done by comparison of the width and center of the BB on the MV
      CBCT. The discrepancy of center between kV-CBCT and MV-CBCT was less than 1mm.
      CONCLUSIONS: Less than 1mm of the geometrical changing to rotation direction for
      MV-detector panel could be recognized by reconstructed images of BB. Using kV-
      and MV-CBCT enable us to perform the simple comparison for geometrical non
      idealities between the kV-IGRT system and the treatment beam. Dr. K. Nakagawa
      received research grant from Elekta.

PMID- 28517566
TI  - SU-E-J-42: Motion Adaptive Image Filter for Low Dose X-Ray Fluoroscopy in the
      Real-Time Tumor-Tracking Radiotherapy System.
AB  - PURPOSE: In the real-time tumor-tracking radiotherapy system, fiducial markers
      are detected by X-ray fluoroscopy. The fluoroscopic parameters should be
      optimized as low as possible in order to reduce unnecessary imaging dose.
      However, the fiducial markers could not be recognized due to effect of
      statistical noise in low dose imaging. Image processing is envisioned to be a
      solution to improve image quality and to maintain tracking accuracy. In this
      study, a recursive image filter adapted to target motion is proposed. METHODS: A
      fluoroscopy system was used for the experiment. A spherical gold marker was used
      as a fiducial marker. About 450 fluoroscopic images of the marker were recorded.
      In order to mimic respiratory motion of the marker, the images were shifted
      sequentially. The tube voltage, current and exposure duration were fixed at 65
      kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube
      current was 100 mA as high dose imaging. A pattern recognition score (PRS)
      ranging from 0 to 100 and image registration error were investigated by
      performing template pattern matching to each sequential image. The results with
      and without image processing were compared. RESULTS: In low dose imaging,
      theimage registration error and the PRS without the image processing were 2.15+/
      1.21 pixel and 46.67+/-6.40, respectively. Those with the image processing were
      1.48+/-0.82 pixel and 67.80+/-4.51, respectively. There was nosignificant
      difference in the image registration error and the PRS between the results of low
      dose imaging with the image processing and that of high dose imaging without the
      image processing. CONCLUSIONS: The results showed that the recursive filter was
      effective in order to maintain marker tracking stability and accuracy in low dose
      fluoroscopy.

PMID- 28517567
TI  - SU-E-J-15: Calculating the Dose from KV Cone Beam CT Within and Outside the
      Treatment Volume Using a Treatment Planning System.
AB  - PURPOSE: To assess the dose from kilovoltage cone beam CT from two image
      acquisition protocols, pelvis and head and neck, by addition of the dose to the
      patient treatment plans. METHODS: A total of 20 patients (10 pelvis and 10 head
      and neck) undergoing radiation therapy were selected and the dose from kV CBCT
      was calculated using a treatment planning system previously commissioned for this
      purpose. The imaging dose was added to the CT images used for treatment planning.
      Daily shifts as a Result of imaging were recorded and applied to imaging beam
      whenever the sum of the shifts exceeded 0.5 cm. The kV CBCT dose can also be
      computed prior to planning, in case of IMRT treatments, and used during
      optimization. RESULTS: The additional dose as a Result of daily CBCT is in the
      order of few cGy for head and neck and up to 90 cGy for the pelvis cases using
      the standard head and neck and pelvis protocols. The pelvic dose is especially
      dependent on patient size, being higher for smaller patients. Due to the low
      energy of the kV CBCT beam, the maximum energy deposition is at or near the
      surface with the highest dose being on the patient's left side for the head and
      neck and on the posterior for the pelvic cases. CONCLUSIONS: Dose from daily
      kilovoltage CBCT can be added to patient treatment plans using previously
      commissioned kV CBCT beams in a treatment planning system. In the case of IMRT
      planning, optimization can be done accounting for kV CBCT dose.

PMID- 28517568
TI  - SU-E-J-53: A Phantom Validation Study of a 3D Background Phase Model for MR
      Thermometry.
AB  - PURPOSE: The proton resonance frequency (PRF) shift method is the most widely
      accepted method for magnetic resonance thermal imaging to provide real-time
      treatment monitoring of thermal therapies. However, the PRF shift technique
      involves the subtraction of a reference phase map, which causes the technique to
      be easily perturbed by tissue motion and other background contaminations. In this
      study, a three-dimensional background phase is estimated in order to create a
      phase reference for each time point. METHODS: A magnetic resonance spectroscopy
      (MRS) sphere was scanned within a 3T MRI scanner employing a 3D fast SPGR
      sequence. Real and imaginary images were acquired to obtain phase images as the
      control. The ability to predict the background phase was investigated by
      systematically removing phase information from the control data set. Data was
      initially removed from a spherical region of interest (ROI) to simulate a region
      where ablativeheating would take place. In a second case, the same spherical ROI
      was removed as well as every other slice to further reduce the amount of existing
      data. A 3D finite element model was implemented to solve the Dirichlet problem
      given a measured phase on the boundary of the simulated available data. RESULTS:
      Line profiles taken through the phantom indicate phase estimates to compare well
      with actual phase measurements. The phase estimation still shows good agreement
      when reducing the amount of data to every other slice. CONCLUSIONS: The 3D multi
      slice temperature estimate potentially provides a robust technique that is not as
      susceptible to through-plane or in-plane motion-induced temperature artifacts as
      compared to thecurrent PRF shift method. The research in this paper was supported
      in part through 1R21EB010196-01.

PMID- 28517570
TI  - SU-E-J-17: Evaluation of Metal Artifact Reduction in MVCTs Using a Model Based
      Image Reconstruction Method.
AB  - PURPOSE: To evaluate the performance of a model based image reconstruction in
      reducing metal artifacts in MVCT systems, and to compare with filtered-back
      projection (FBP) technique. METHODS: Iterative maximum likelihood polychromatic
      algorithm for CT (IMPACT) is used with pair/triplet production process and the
      energy dependent response of detectors. The beam spectra for in-house bench-top
      and TomotherapyTM MVCT are modelled for use in IMPACT. The energy dependent gain
      of detectors is calculated using a constrained optimization technique and
      measured attenuation produced by 0 - 24 cm thick solid water slabs. A cylindrical
      (19 cm diameter) plexiglass phantom containing various central cylindrical
      inserts (relative electron density of 0.28-1.69) between two steel rods (2 cm
      diameter) is scanned in the bench-top [the bremsstrahlung radiation from 6 MeV
      electron beam passed through 4 cm solid water on the Varian Clinac 2300C] and
      TomotherapyTM MVCTs. The FBP reconstructs images from raw signal normalised to
      air scan and corrected for beam hardening using a uniform plexi-glass cylinder
      (20 cm diameter). IMPACT starts with FBP reconstructed seed image and
      reconstructs final image at 1.25 MeV in 150 iterations. RESULTS: FBP produces a
      visible dark shading in the image between two steel rods that becomes darker with
      higher density central insert causing 5-8 % underestimation of electron density
      compared to the case without the steel rods. In the IMPACT image the dark shading
      connecting the steel rods is nearly removed and the uniform background restored.
      The average attenuation coefficients of the inserts and the background are very
      close to the corresponding theoretical values at 1.25 MeV. CONCLUSIONS: The dark
      shading metal artifact due to beam hardening can be removed in MVCT using the
      iterative reconstruction algorithm such as IMPACT. However, the accurate
      modelling of detectors' energy dependent response and physical processes are
      crucial for successful implementation. Funding support for the research is
      obtained from "Vanier Canada Graduate Scholarship" and "Canadian Institute of
      Health Research".

PMID- 28517571
TI  - SU-E-J-55: Development of a Novel Cableless Radiolucent RF Coil for MR-Guided
      Radiation Therapy (MRgRTTM).
AB  - PURPOSE: To demonstrate the feasibility of a novel radiotherapy-compatible
      cableless radiofrequency (RF) coil for an MR-guided radiation therapy(MRgRTTM)
      system that employs a movable MRI system. This coil technology will expedite
      clinical workflow by eliminating need for coil connections and cables, allowing
      RF coils to remain in place for treatment. METHODS: We quantified radiation
      transmission factors and surface dose changes for aluminum (Al), copper (Cu) and
      FR4 substrate typical of RF coils using a Varian Trilogy linear accelerator. Ion
      chamber measurements were performed by applying 6 MV fields of various sizes
      through sheets of each material and metal-substrate combination. These
      measurements were repeated with the materials on a standard treatment couch.
      Material optimization provided input to build a prototype cableless coil and
      representative coil segment for surface dose measurements. RESULTS: We observed
      expected patterns for radiation field sizes between 1 cm * 1 cm and 25 cm * 25 cm
      and expected variation with off-axis distances < 12 cm. All metal-substrate
      combinations had transmission factors > 0.996, the lowest being Cu-FR4. Relative
      surface dose increases were similar for Cu-FR4 (3.9) and Al-FR4 (3.3)
      combinations. Couchtop relative surface dose increases were much greater than
      coil materials alone and did not increase substantially with the addition of coil
      materials (couch-only = 6.6, couch with Cu-FR4 = 7.3). Relative surface dose
      increase was 6.23 for prototype coil segment with capacitor, but the capacitors
      are not in the primary beam path for the coil design. CONCLUSIONS: Results
      indicate surface dose effectsare the dominant consideration in RF coil design for
      MRgRT. Similar Cu and Al surface dose effects suggest Cu is a viable coil
      inductor material for this application. Given that coil material contribution to
      surface dose is small compared to the couchtop material it is feasible to keep
      this cablelesscoil in place during radiation treatment. This work has received
      research personnel support from IMRIS.

PMID- 28517569
TI  - SU-E-J-26: Automated Estimation Method of Patient Setup Errors Using Simulated
      Portal Images for Prostate Cancer Radiotherapy.
AB  - PURPOSE: We developed a novel automated estimation method for patient setup
      errors based on simulated and real portal images for prostate cancer
      radiotherapy. METHODS: The estimation of patient setup errors in this study was
      based on a template matching technique with a cross-correlation coefficient and
      Sobel filter between the real portal image and localized pelvic template of
      reference image, which were DRR (digitally reconstructed radiography) images and
      simulated portal images. The simulated portal image was derived by projecting a
      CT image according to an inverse exponential power law of x-ray attenuation for a
      water-equivalent path length of each voxel of the CT image on each ray from a
      source to each pixel on the EPID (electric portal imaging device). A localized
      pelvic template of each patient in AP (anterior-posterior) or lateral view was
      automatically extracted from the DRR or simulated portal images by cropping a
      rectangular region, which was determined by using the mean pelvic template and
      four anatomical feature points. We applied the proposed method to three prostate
      cancer cases, and evaluated it using the residual error between the patient setup
      error obtained by proposed method and the gold standard setup error determined by
      two radiation oncologists. RESULTS: The average residual errors of the patient
      setup error for the DRR and simulated portal images were 0.79 and 1.26 mm in the
      left-right (LR) direction, 3.17 and 2.05 mm in the superior-inferior (SI)
      direction, 1.69 and 5.82 mm in the anterior-posterior (AP) direction, 3.84 and
      6.94 mm in Euclidean distance (ED), respectively. If we used the simulated portal
      image for LR and SI directions and the DRR image for AP direction, the Euclidean
      distance was 3.22 mm. CONCLUSIONS: The proposed method has a potential to
      correctly estimate patient setup errors for prostate cancer radiotherapy.

PMID- 28517572
TI  - SU-E-J-28: Comparison of IGRT Shift Data Between Prostate Gland and Prostate Bed
      Obtained from Ct-On-Rails.
AB  - PURPOSE: The daily shifts of prostate gland have been intensively reported in
      literatures. However, few papers reported daily shifts of prostate bed due to
      several practical difficulties (e.g. limited soft tissue contrast in MVCT and
      CBCT and significant deformation of prostate cavity). We have routinely performed
      IGRT for both prostate gland and bed with ct-on-rails, and the superior image
      quality allows us not only to differentiate both bony anatomy and soft tissue
      contrast of prostate gland and bed. In this study, we investigated if the shift
      of prostate bed is signifiant difference from that of prostate gland. METHODS: we
      reviewed shift data of 50 prostate gland patients who underwent 43 fractions and
      22 patients of prostatectomy underwent 37 fractions. In total 2150 CT scans were
      reviewed for prostate gland and 814 scans for prostate bed. RESULTS: Of the
      reviewed 814 CT images from 22 prostate bed patients, the standard deviation of
      shift was found to be 5.9 mm in AP direction (ranges from -22.4mm to 22mm), 3.2mm
      in SI direction (ranges from -14mm to 14mm), and 4.1mm in lateral direction
      (ranges from -15mm to 22mm). Of the 2150 CT images of prostate gland from 50
      patients, the standard deviation of the shift was found to be 5.4 mm in AP
      direction (-20mm to 18 mm), 5.0mm in SI direction (-26mm to 20mm), and 4.3mm in
      lateral direction (range from-15 to 30mm). F tests of systematic /random shift
      distribution in three orthogonal directions between prostate gland and prostate
      bed were subsequently performed, it was found that the systematic shift in SI
      direction for prostate bed is smaller than for prostate gland (p=0.003).
      CONCLUSIONS: Our result suggests no significant difference existing in shift
      between prostate bed and gland. Therefore strategies for daily prostate gland
      motion can be directly applied to prostate bed.

PMID- 28517573
TI  - SU-E-J-37: Radiation Dose during Chemoembolization: A Predictive Model.
AB  - PURPOSE: To identify variables correlated with radiation dose during hepatic
      chemoembolization, quantify their individual impact, and apply these findings to
      build a dose prediction model. METHODS: A retrospective review of 77 patients
      undergoing hepatic chemoembolization between 1/2010-10/2010 was performed.
      Variables included: Radiation dose metrics[DAP, CD, number of cone beam CT and
      fluoroscopy time] and clinical parameters(BMI, session number, extrahepatic
      embolization, lesion number, chemoembolization regimen and lobe(s) treated). CD
      was the primary outcome measurement used for the dose model. Univariate and
      multivariate linear regression models were used to assess the association between
      dose metrics and predictive variables and assess the relative impact of each
      variable on dose. Variables were considered statistically significant at the
      p<0.05 level. Coefficient of determination(R2)and root mean square error(RMSE)
      were calculated for CD. R2 was used to evaluate goodness of fit and RMSE was used
      to establish a measurement of the typical size of the error in predicting the
      cumulative dose. RESULTS: Based on the multivariate analysis: higher BMI,
      regimen, single lesions, 1 degrees  tumor and initial session were statistically
      significant and incorporated into the following dose prediction model: Predicted
      Dose(mGy)= -672+BMI(56.3)+558(session #1)+1789(extrahepatic a. embolized)+232(1
      degrees tumor)+[-667(2-4 lesions)or - 12(>5 lesions)]+[370(dox-bead regimen)or
      1618(ethiodol based regimen)]. Plots of the predicted vs actual CD were performed
      and the adjusted R2 for CD is 52.9%(RMSE = 697). The model is accurate at
      predicting 52% of the variation. When the model predicts a dosage of 1000 or 2000
      mGy the actual dose interval ranges from 519-2519 mGy or 384-3616 mGy,
      respectively. CONCLUSIONS: Creating a radiation dose prediction model is
      feasible. This is the first known attempt at creating a dose model for image
      guided intervention and refinements to the model will be required to improve its
      accuracy. Prospective dose modeling will become more relevant as the cost benefit
      analysis of radiation exposure enters the decision making process in patient
      care. Alda Tam: Angiodynamics Inc., research funding Joseph Steele: MedicaSafe,
      Inc ownership Intelliject medical ownership INTIO medical consultant/ownership
      Caymus Medical ownership Cayenne Medical ownership.

PMID- 28517574
TI  - SU-E-J-10: Accuracy of Image Guidance Using Cone-Beam CT with Multiple Breath
      Hold Using Active Breathing Coordination.
AB  - PURPOSE: To complete a CBCT for a treatment using ABC, multiple breath hold (BH)
      (>3) were used due to the slow gantry rotation and the short BH period. Inter-BH
      tumor position variability may introduce distortion in the reconstructed images.
      This study aims to determine a threshold of the inter-BH scan displacement so
      that the inconsistency can be identified from the CBCT images. METHODS: A
      numerical phantom was constructed to represent the thorax region of a human body.
      To simulate the inter-BH displacements, known magnitudes of motion (s = 0, 1, 3,
      5 mm) along the longitudinal direction were introduced for the 'tumor' and
      'diaphragm' in the phantom. Two different irregular motion patterns (s1=s3=/=s2
      and s1=/=s2=/=s3) during CBCT scans were tested. Furthermore, a physical phantom
      with a movable insert was scanned using a commercial CBCT system. The insert of
      the phantom was programmed to move in the longitudinal direction according to the
      same motion patterns as designed in the numerical simulations. Subsequently, nine
      CBCT's in 'half-fan' mode for the physical phantom were acquired with the insert
      in various positions. These CBCT images were then fused to the reference CT by
      aligning to either the body of the phantom or the 'tumor' inside the insert.
      RESULTS: Based on numerical simulation, position variation >1mm can be observed
      from the reconstructed CBCT images. Based on acquired CBCTs of the physical
      phantom, position variations of >3mm or 5mm were observed, depending on the
      motion pattern during the data acquisition. Because of the use of half-fan mode,
      we observed the order of position displacements of the tumor during CBCT
      acquisition drastically affected the outcome of imaging registration.
      CONCLUSIONS: Using ABC device, the inter-BH variability during a CBCT acquisition
      affects accuracy of tumor localization. A patient individualized planning margin
      might be necessary to account for this effect.

PMID- 28517575
TI  - SU-E-J-48: Real Time Image Guided Localization in SBRT Lung/Liver Patients
      Radiation Treatment.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) lung/liver patientradiation
      treatment requires high precision of patient position and target localization.
      For SBRT lung/liver patients positioning, cone beam CT imaging has been widely
      used, generally with zero couch rotation. The purpose of this study is to
      implement Stereotactic radiation surgery (SRS) patient positioning technology to
      SBRT by expanding patient positioning with couch rotation. METHODS: A Varian(r)
      Novlis Tx for SRS treatment wasused to treat SBRT lung/liver patients
      implementing CBCT. BrainLAB(r) X-ray imaging system in conjunction with optical
      guidance is primarily used for SRS patients. CBCT and X-ray imaging system were
      independently calibrated with 1.0 mm accuracy. The X-ray imaging system was
      implemented through BrainLAB(r) ExacTrac system with CBCT localized position at
      the initial zero position for the X-ray imaging system. For the other couch
      positions, X-ray images were fused with patient DRRs for positioning. RESULTS:
      Based on daily imaging QA records for a period oftwo years, the longitudinal,
      vertical and lateral coordination between CBCT and X-ray imaging average 0.3+/
      0.5, 0.2+/-0.5 and 0.5+/-0.5 mm. The shiftfrom the CBCT imaging isocenter to the
      X-ray imaging isocenter is 0.5+/-0.5 mm accuracy for a 24-month period of
      tracking. Patient position accuracy: After initially localizing the patient with
      CBCT at the zero couch position, the patient was positioned with the X-ray
      imaging system. The computed translational and rotational shift accuracy are
      0.5+/-0.5 mm and0.4+/-0.3 degree respectively, based on 66 SBRT lung/liver
      patients couchrotations. CONCLUSIONS: Accurate coordination of CBCT and X-ray
      imaging in conjunction with optical imaging guidance can be expanded to patient
      positioning with couch rotation. The X-ray imaging capability at rotated-couch
      positions improved the physician confidence level during SBRT lung/liver patients
      treatment.

PMID- 28517576
TI  - SU-E-J-21: An Intercomparison of Imaging Performance of Two Linac-Mounted Imaging
      Systems Used in Radiation Therapy: TrueBeam and Trilogy.
AB  - PURPOSE: To evaluate and compare the performance of the imaging systems of two
      linear accelerators, used in radiation therapy. The study includes the following
      imaging components: electronic portal imaging device (EPID), kilovoltage
      projection imaging and kilovoltage cone-beam CT. METHOD AND MATERIALS: The
      imaging systems mounted on the Varian Trilogy (Varian Medical Systems) and Varian
      TrueBeam, were evaluated. Image quality of two EPID systems (ASI-1000) and the
      two kV flat panel imagers (PaxScan 4030CB) was evaluated in terms of spatial
      resolution and contrast-to-noise ratio (CNR) using the QC-3 and QCkV-1 phantoms
      (Standard Imaging, Inc.). Cone-beam CT image sets of the CatPhan phantom (The
      Phantom Lab.) were obtained for standard dose head (100kVp, 0.4mAs per
      projection) and body (125kVp, 1.04mAs) protocols. Imaging parameters of the
      default clinical settings were used. The end points of the comparison were
      spatial resolution, CT number linearity, low contrast detectability and image
      uniformity. Analysis of all types of images was performed by the PIPSpro software
      (Standard Imaging). RESULTS: The critical frequency (f50 in units of lp/mm) of
      0.446 and 0.403 were obtained for TrueBeam and Trilogy MV detectors,
      respectively. The CNR was found double for Trilogy. For kilo-voltage detectors
      the f50 was 1.337 and 1.363, while the CNR was better by 6% in Trilogy machine.
      The CBCT comparison showed a 30% higher uniformity index for the TrueBeam system
      for pelvis protocol and 50% higher head. No significant difference was found in
      low contrast detectability and CT number linearity and resolution, 5 lp/mm. The
      Trilogy image was noisier by 35% and 30% for pelvis and standard head protocol,
      respectively. CONCLUSIONS: The critical frequencies of both kV and MV detectors
      were found better in TrueBeam, while CNRs were found better in Trilogy. TrueBeam
      preformed superiorly in CBCT in terms of image uniformity and noise level.

PMID- 28517577
TI  - SU-E-J-59: Dual Imaging Guided Localization System for Spine Radiosurgery.
AB  - PURPOSE: To compare localization accuracies between an ExacTrac and cone beam
      computed tomography (CBCT) systems for single fraction spine adiosurgery. The
      work also aimed to evaluate the inherent systematic deviation of both ExacTrac
      and CBCT systems to achieve highly accurate localization in the spine
      radiosurgery. METHODS: ExacTrac and CBCT imaging systems were evaluated using the
      linac isocenter as the mutual reference point. First, a BB was placed in an
      anthropomorphic pelvic phantom. The phantom was localized with both imaging
      systems and the procedure was repeated 12 times. These results were used to
      devise a localization protocol using both imaging systems in spine radiosurgery,
      and employed for 51 patients (81 isocenters) prescribed for single fraction
      treatment. The displacement discrepancy between the isocenter and two systems
      were quantified in four dimensions (three translations, one rotation). A
      Student's two-tailed t-test was used to test for significant differences between
      the two imaging systems. RESULTS: The phantom study showed 1.4+/-0.5, 0.6+/-0.5,
      and 0.1+/-0.5 mm differences between the two imaging systems in the
      anterior/posterior (A/P), superior/inferior (S/I) and left/right (L/R)
      directions, respectively. The angular difference was minimal along all three
      axes. The patient study revealed similar isocenter discrepancies between ExacTrac
      and CBCT of 1.1 +/- 0.7 mm, 1.0+/-0.9 mm, and 0.2+/-0.9 mm in the A/P, S/I, and
      L/R directions, respectively, with the A/P and S/I directions showing statistical
      significance ((t(80) = 13.5 and 7.6 respectively, p = 0.000). The couch yaw
      discrepancy was 0 +/- 0.3 degrees . Overall, 1 mm systematic differences were
      observed in the A/P and S/I directions between ExacTrac and CBCT localization
      systems, both in phantom and patient. A procedure was developed to mitigate this
      systematic discrepancy. CONCLUSIONS: These findings have justified our patient
      localization tolerance levels of 2 mm translation and 1 degree rotation for spine
      SRS treatment.

PMID- 28517579
TI  - SU-E-J-04: Initial Experience with 4D-CBCT for Lung Cancer: Physician
      Verification of Computed Shifts Remains Necessary.
AB  - PURPOSE: Four-dimensional cone-beam CT (4D-CBCT) is a novel imaging technique
      used to guide treatment setup for patients with pulmonary lesions by providing
      additional information about tumor motion at the time of treatment. This study
      aimed to evaluate the efficacy of the 4D-CBCT capability in ensuring accurate
      patient setup during SBRT. METHODS: Twelve patients with pulmonary lesions were
      imaged pre-treatment with Elekta XVI4.5 using the Symmetry protocol resulting in
      a respiratory correlated 4D-CBCT. Reconstruction produced 10 phased-based and one
      average 3DCT image set. Patient shifts were derived from contour-based(mask)
      registration driven by the weighted average of shifts from each phased CT(4D
      shifts). Physicians reviewed registration and manually adjusted shifts based on
      visual registration. We exported the average 3DCT to MIM Vista Software 5.1.1 in
      reference volume coordinates and manually fused to the reference CT. All manual
      fusions were contour-based registrations performed by a single observer. No
      rotations were permitted in manual fusion to mimic clinical procedure.
      Translational 3D shifts from manual fusion were compared to 4D(automatic
      registration) shifts and final physician-corrected shifts. RESULTS: Mean
      differences between 4D and 3D shifts in lateral, longitudinal, and vertical
      directions were 1.07mm, 5.92mm, and 1.43mm, respectively. Mean differences
      between physician-corrected and 3D shifts were 1.41mm, 4.83mm, and 1.61mm.
      Differences between 4D shifts and 3D shifts increased with increasing tumor
      motion. One patient had consistently large longitudinal differences between 4D
      and 3D shifts (mean=3.0cm). Further review revealed poor 4D registration(via mask
      and clipbox) on the XVI system which was corrected by physician adjustment prior
      to treatment. CONCLUSIONS: 4D-CBCT is a valuable imaging tool in patient setup.
      Physician review of contour-based registration is imperative in preventing a
      geometrical miss. Caution must be employed in tumors that exhibit a large degree
      of motion. Further research is necessary in determining functional limits of the
      4D-CBCT system.

PMID- 28517578
TI  - SU-E-J-32: Evaluation of the Dosimetric Accuracy of Stereotactic Radiosurgery
      with Cone-Beam Computed Tomography Localization.
AB  - PURPOSE: To evaluate the dosimetric accuracy of stereotactic radiosurgery (SRS)
      with cone-beam computed tomography (CBCT) guided patient localization. METHODS: A
      Novalis TX linear accelerator with high definition multileaf collimator (HDMLC)
      was used for SRS treatments. 20 patients immobilized with the noninvasive
      BrainLab U-frame system and thermoplastic mask were selected to evaluate the
      dosimetric accuracy of CBCT image-guided SRS by the BrainLab iPlan Phantom
      Mapping module. The contours of the PTV and critical organ were transferred
      directly from the planning CT and MR images to the CBCT images after image
      registrations. The delivered dose distributions could be calculated and analyzed
      by copying the original treatment plans to the CBCT images and assigning the
      treatment isocenters on the CBCT images according to the couch shifts acquired
      after planning CT and CBCT image registrations. The CT electron density
      calibration curve used for original plans was also applied for the CBCT-based
      planning. RESULTS: The average minimum dose, mean dose, and maximum dose in PTV
      of the original plans and the CBCT plans were 95.45%+/-3.80% and 92.88%+/-3.25%,
      110.59%+/-1.81% and 110.11%+/-2.40%, 116.55%+/-3.11% and 115.93%+/-2.78%,
      respectively. In the original treatment plans, the average 100% prescription dose
      coverage of GTV and PTV were 99.99% and 99.81%, respectively. In the CBCT plans,
      the average 100% prescription dose coverage of GTV and PTV were 99.90% and
      98.20%, respectively. The average conformity index of the original plans and the
      CBCT plans were 1.846 and 1.863, respectively. CONCLUSIONS: Data demonstrated
      that the dose distributions calculated in the CBCT images were comparable to the
      original treatment plans. The CBCT plans only indicated a slightly higher
      conformity index and lower average minimum dose, mean dose, maximum dose, GTV
      coverage, and PTV coverage compared to the original treatment plans. Therefore,
      the CBCT guided localization was considered effective to assure dosimetric
      accuracy in SRS.

PMID- 28517580
TI  - SU-E-J-41: Fluoroscopy Based Adaptive Setup Approach for Thoracic Cancer IGRT.
AB  - PURPOSE: To develop a fluoroscopy imaging based approach that can determine the
      magnitude and phase variation in respiratory motion against the treatment
      planning images in order to quantify the online patient setup deviation in
      thoracic cancer IGRT for the real time adaptive patient positionadjustment.
      METHODS: A numerical phantom was generated to test the strength of the approach.
      The 2D phantom consist a static outside wall and an inner target moving in
      temporal pattern similar to the respiratory motion. Four motion parameters:
      frequency (0.5Hz~2Hz), amplitude (40~60mm), position offset (5~10mm), and phase
      shift (starting phase 0, 45, and 90 degrees) vary to generate phantom image sets
      with different motions. White noise of level SNR=5 was added to all phantom
      images to simulate the impact of clinical image quality. A manifold based machine
      learning technique was used to construct the respiratory motion model under
      thestandard condition (frequency 1 Hz, amplitude 50mm, and no position offset
      and/or phase shift). Then the phase and position shift in other phantom image
      series were quantified by finding the MAP solution to fit theembedded motion to
      the standard motion model. RESULTS: The proposed approach can detect the
      variation in motion patterns between two image sets. The method is insensitive to
      frequency changes and image noise up to SNR=5, but is very effective at capturing
      and quantifying the change in motion amplitude, position shift, and also the
      phase shift. CONCLUSIONS: This work proposed an effective mathematical approach
      to quantify the difference in motion between the pre-treatment images and the
      treatment planning images by extraction of the motion model in fluoroscopy images
      using the machine learning technique. By applying the approach during online
      patient setup, the positioning deviation can be separated from the respiratory
      motion and adjusted to minimize the normal tissue toxicity in gated IGRT.

PMID- 28517581
TI  - SU-E-J-14: Evaluation of Mechanical Accuracy of Electronic Portal Imaging Devise
      on Its Use in Patient Specific IMRT QA.
AB  - PURPOSE: Electronic portal imaging devices (EPID) have been used for both in vivo
      dosimetry and in vitro dose verification in intensity modulated radiotherapy
      (IMRT). This study is to investigate the effect of EPID mechanical precision on
      the accuracy of measured dose distribution. METHODS: EPID energy fluences (dicom
      images) of H&N IMRT fields were collected daily on two Varian LINACs (Clinac-iX &
      Trilogy) over 4-week period. The energy fluences were converted to doses using
      EPIDoseTM (Sun Nuclear Corp). Mechanical deviations of EPIDs could be divided
      into two components: one with inherent detector center misalignment from the beam
      central axis, another caused by the 'sagging effect' from gantry rotation. The
      first component was detected by 'best matching' of the measured and calculated
      dose at zero gantry angle (G=0). The second component was computed by 'best
      matching' the 10*10cm field defined by MLC at G=0, 90,180, and 270, separately. A
      'shift' was generated by the combination of these two components and then applied
      to correct the measured dose at the corresponding gantry angle for the IMRT
      field. RESULTS: Inherent misalignment of the detector's center and the 'sagging'
      deviation were found to be 1-2 mm and 1-5 mm, respectively for both LINACs. Each
      component was found very stable (change < 1mm) over the 4-week observational
      period. Using a Gamma index of 2%/2mm (DD/DTA), the 'shift' increased the average
      passing rate from 59% to more than 92%. On the other hand, blindly applying 'auto
      shift' from commercially available software to obtain the best match would
      compound true QA issues with units' misalignments. CONCLUSIONS: A false
      'mismatch' between measured and calculated dose distribution caused by mechanical
      inaccuracies of EPID could be avoided by measuring the two components identified
      in this study. One should examine the mechanical precision of equipment prior to
      clinical use of EPID dosimetry.

PMID- 28517582
TI  - SU-E-J-52: Validation of 3D Structure Projection Onto 2D DRR in Commercial
      Treatment Planning Systems.
AB  - PURPOSE: The use of structure overlay on setup DRRs can aid the image alignment
      procedure for daily image-guided setup procedures. However, the accuracy of a 3D
      region-of-interest (ROI) projected on a 2D digitally reconstructed radiograph
      (DRR) has rarely been evaluated quantitatively. The goal of this study is to test
      the accuracy of two commercial treatment planning systems (TPS) in producing
      overlay structures on setup DRRs. METHOD AND MATERIALS: We designed a novel
      method to identify landmarks which were on the boundary of the projected ROI on a
      DRR. The 3D ROIvolume is composed of a stack of 2D curves. We first
      mathematically project each 2D curve onto a beams-eye-view (BEV) plane. Next, we
      detectthe boundary points of the projected curves. Those boundary points serve
      aslandmarks. Finally, we project the binary mask of the 3D ROI volume using ray
      tracing method onto the BEV plane. This projected binary mask is used to exclude
      the false landmarks. Once those landmarks are detected, wecompute the distance
      between the landmarks and ROI outlines from the TPS. RESULTS: We applied our
      validation method to 13 ROIs from a lung patient and 4 simulated ROIs on 2 BEV
      DRRs for two different TPS (Eclipse and Pinnacle). Average distance between the
      landmarks and ROIoutlines was 0.5mm for both Eclipse and Pinnacle approaches,
      which is close to the pixel resolution of the DRR. The maximum distance
      andaverage maximum distance was 2mm and 1 mm, respectively, for both TPS.The
      maximum distance occurred at points where the ROI curve has a sharpchange between
      slices. CONCLUSION: The accuracy of Eclipse and Pinnacle ROI projection method
      seems to be acceptable to within 1mm althoughprojection error can be as large as
      2mm when structure shape has a sharp variation from one slice to the next.

PMID- 28517583
TI  - SU-E-J-25: Dosimetric Characterization of an OBI System Using Gafchromic XRQA2
      Film.
AB  - PURPOSE: Accurate knowledge about the radiation dose due to the imaging component
      of an OBI supported linear accelerator is very important. Though films provide
      excellent spatial resolution, there are problems regarding sensitivity and energy
      dependence at kV energies. XRQA2 film (0.1-20 cGy) is primarily for measurements
      in kV range. We demonstrate their use for absolute dosimetry for an OBI system.
      METHODS: H&D curves were generated using a kV therapy x-ray unit in the range of
      0-15 cGy. A 25-cm diameter water-equivalent cylindrical phantom with 2.5-cm thick
      slabs was used on Varian Trilogy linac. XRQA2 films were cut into circular
      diameter and sandwiched between 2 slabs of the cylindrical phantom to measure the
      percentage depth dose of the CBCT scans. Additional film pieces were wrapped
      around the cylinder for surface dose. To get sufficient signal, 5 CBCT scans were
      taken per imaging acquisition template e.g. head standard dose. After 24 hours
      post-irradiation, films were scanned using Epson V700 scanner in reflection mode.
      Only red channel was used for dosimetric analysis using RIT software. RESULTS:
      High-Quality head acquisition template resulted in a dose at 0.2, 1.3, 2.7, and
      2.7 cGy on AP, left-lateral, posterior and right-lateral positions of the
      phantom, respectively. Low-quality thorax acquisition resulted in 1.4, 1.6, 1.5,
      and 1.4 cGy. The PDD at 12.5-cm (isocenter) was of the order of 40%. While the
      PDD was fairly uniform from left to right, the PDD along the AP/PA direction were
      showing almost continuous fall off with PDD at isocenter of ~40%. Analysis of low
      quality head PDDs show little fall off dose with depth though the overall
      magnitude was less with PDD at the isocenter only marginally lower than the
      maximum along the medial and anterior posterior axis. CONCLUSIONS: Gafchromic
      XRQA2 film provides a useful tool to evaluate and characterize an OBI system.

PMID- 28517585
TI  - SU-E-J-27: Effects of Metal Artifacts of KV and MV CT Images on Structure
      Delineation and Tissue Electron/Mass Density Calculation.
AB  - PURPOSE: To quantitatively evaluate effects of image artifacts of hip prostheses
      on the accuracy of structure delineation and tissue density calculation on kV and
      MV CT images. METHODS: Five hip prostheses made of stainless steel, titanium and
      cobalt chrome alloys were positioned inside a water tank and scanned respectively
      on a Philips CT and a Tomotherapy Hi-Art unit. Prostheses were positioned to
      mimic single and bilateral implantations. Rods of tissue materials of lung, water
      and bone were placed at locations next and distal to metal implants near femoral
      head, neck and stem of prostheses. kV and MV CT scans were repeated for each
      placement. On CT images, cross-sectional outlines of metal implants and tissue
      rods were delineated. Densities of rod materials were determined and compared to
      the true values. RESULTS: Metal artifacts were severe on kV CTs and minimal on MV
      CTs. Cross-sectional outlines of metal implants and tissue rods on kV CTs were
      severely distorted by artifacts while those on MV CTs remained clearly
      identifiable. For kV CTs, deviations of measured tissue density from true value
      were up to 51.3%, 30.6% and 40.9% respectively for lung, bone and solid water.
      The magnitude of deviation was generally larger at locations closer to metal
      implants and greater with bilateral implants than single implant. For MV CTs,
      deviations of measured density from true value were less than 6% for all three
      tissue materials either with single or bilateral implants. Magnitude of deviation
      appeared to be uniform and independent of locations relative to metal implants.
      CONCLUSIONS: High Z metal artifacts on kV CTs can have severe impact on the
      accuracy of structure delineation and tissue density calculation, while on MV
      CTs, the impact is substantially less and insignificant. MV CTs should be
      considered for treatment planning on patients with high Z metal implants.

PMID- 28517584
TI  - SU-E-J-35: A Model for the Simulation of EPID Measurements in the BeamNRC Monte
      Carlo Package.
AB  - PURPOSE: The intent of this study was to create a virtual model of a simple
      Electronic Portal Image Device (EPID) in the BeamNRC Monte Carlo package which
      would simulate EPID measurements taken in vivo. METHODS: A typical accelerator
      was created in the BeamNRC software using published 6MV spectra from Mohan, et.
      al. and the basic head design of a Varian accelerator head. The particle fluence
      at the level of the mylar window was output into a planar 'phase space' file. The
      output of this accelerator was delivered to a phantom with a 1 mm thick slab of
      water acting as the detector array using the DosXYZ package. Additionally, the
      fluence from the same geometry was computed at the level of the virtualEPID
      (vEPID). The simulations were run for 2*2, 5*5, 10*10, 20*20, and 25*25 field
      sizes, as well as a simple IMRT field. The results of the open field simulations
      were then used for the parameterization of a deconvolution kernel using the form
      described by Renner, et. al. RESULTS: The simulations were run with sufficient
      histories to produce a 1% uncertainty in the resulting fluence and dose matrices
      in the high dose/fluence region of the output. Additional software was created to
      convert 'phase space' files to fluence in the same grid as the vEPID. A final
      software package was written to iteratively determine the exponential fitting
      parameters described in Ritter, et. al. to deconvolve the detector function from
      the fluence measurements. CONCLUSIONS: The system will allow one to simulate both
      EPID measurements, as well as remove the detector function from vEPIDsimulations
      for further use in fluence studies using BeamNRC. This will allow one to simulate
      a system for in vivo patient measurements using an EPID to study without the need
      for time on a medical accelerator, and without contributing additional radiation
      fatigue to the EPID device.

PMID- 28517586
TI  - SU-E-J-36: A Flexible Integration of Key Technologies in Image-Guided
      Radiotherapy for Accurate Radiotherapy System (ARTS-IGRT).
AB  - PURPOSE: Image-guided radiotherapy (IGRT) is becoming increasingly important in
      the planning and delivery of radiotherapy. With the aim of implementing the key
      technologies in a flexible and integrated way in IGRT for accurate radiotherapy
      system (ARTS), a prototype system named as ARTS-IGRT was designed and completed
      to apply main principles in image-guided radiotherapy. METHODS: The basic
      workflow of the ARTS-IGRT software was completed with five functional modules
      including management of patient information, X-ray image acquisition, 2D/2D
      anatomy match, 2D/3D match as well as marker-based match. For 2D/2D match, an
      image registration method was proposed based on maximization of mutual
      information with multi-resolution and regions of interest. For the 2D/3D
      registration, optimizations have been employed to improve the existing digitally
      reconstructed radiography generation algorithm based on ray-casting, and also an
      image registration method based on implanted markers with different numbers was
      adopted for 3D/3D match. In additional, the kV X-Ray imaging on rail device was
      finished for a better internal anatomy image checking at any angle. Together with
      an infrared device, a positioning and tracking system was developed as well for
      accurate patient setup and motion monitoring during each treatment. RESULTS: A
      lot of tests were carried out based on the head phantom to testify the
      availability of the improved algorithms. Compared with a set of controlled
      experiments adopted on the released commercial IGRT platform in the hospital, the
      functions of both software and hardware were testified comprehensively. The
      results showed a validity verification of ARTS-IGRT. CONCLUSIONS: The accuracy
      and efficiency of ARTS-IGRT on both software and hardware proved to be valid. And
      also with a flexible and user-friendly interface it can meet the principles of
      clinical radiotherapy practice. Supported by the Natural Science Foundation of
      Anhui Province (11040606Q55) and the National Natural Science Foundation of China
      (30900386).

PMID- 28517588
TI  - SU-E-J-47: Evaluation of the Mismatches Between DRR's and Port Films for IMRT
      Fields.
AB  - PURPOSE: To quantify the frequency and magnitude of mismatches between the MLC
      shape on the DRR created by the Pinnacle planning system and the corresponding
      port film MLC shape generated by the Mosaiq record-and-verify system for IMRT
      fields. METHODS: A retrospective review was made of the most recent 60 patients
      to receive IMRT at our clinic. The MLC shape on the DRR created by the Philips
      Pinnacle planning system for each treatment field was reviewed (573 fields total)
      and compared with the MLC shape of the port film image, which was generated by
      the Mosaiq treatment planning system. RESULTS: Of the 60 patients studied, 20 had
      at least one leaf mismatched between the MLC shape on the DRR and port film (142
      of the 573 fields). Of the affected cases, on average 59% of the fields had a
      mismatch. The affected fields had an average of 6.7 leaves mismatched with a mean
      discrepancy of 27mm. The average maximum discrepancy for each affected patient
      was 69mm. Discrepancies were most common for head and neck cancers. CONCLUSIONS:
      The MLC shape Mosaiq generates for the port film is the CIAO, or Complete
      Irradiated Area Outline, which is the area that is actually treated. The Pinnacle
      DRR displays the maximum leafmotion, which can be different for larger fields in
      which the MLC leaves abut within the collimator jaw opening. The discrepancy can
      create substantially different MLC shapes. The problem can be solved by not
      filming the MLC shape and only using the films for isocenter placement; however,
      displaying the area receiving treatment can be a useful safety check, possibly
      preventing a treatment error. The persons assessing the films must be aware of
      this issue and evaluate the films carefully.

PMID- 28517587
TI  - SU-E-J-09: Performance Optimization of Thick, Segmented Scintillators for
      Radiotherapy Imaging.
AB  - PURPOSE: Thick segmented scintillators, incorporating a 2-dimensional matrix of
      optically-isolated scintillator elements, have shown considerable potential for
      improving the performance of megavoltage active matrix, flat-panel imagers (MV
      AMFPIs). While over a factor of 20 improvement in DQE at zero spatial-frequency
      has been demonstrated for prototypes incorporating CsI(Tl) and BGO scintillators,
      less-than-optimal element-to-element alignment (misalignment) as well as mis
      registration to the underlying AMFPI array pixels can result in spatial
      resolution loss, reducing DQE improvement at higher spatial frequencies. In this
      presentation, a method to restore spatial resolution and DQE, based on the use of
      a high resolution AMFPI array along with special binning techniques, is
      investigated. METHODS: The effect of misalignment and mis-registration of
      segmented scintillators on imaging performance was investigated theoretically and
      empirically through determination of the modulation transfer function (MTF) and
      DQE, as well as through realization of reconstructed images of a phantom in a
      cone-beam CT geometry. The empirical investigation, which was conducted using a 6
      MV photon beam, employed a prototype BGO segmented scintillator consisting of
      120*60 elements separated by 50 MUm-thick septal walls and an element-to-element
      pitch of 1016 MUm. The scintillator was coupled to a higher resolution 127-MUm
      pitch AMFPI array. RESULTS: Misalignment and mis-registration result in
      significant degradation of spatial resolution, leading to DQE reduction at non
      zero spatial frequencies. While mis-registration for a well-aligned scintillator
      can be overcome through 8*8 binning of the array pixels to match the scintillator
      elements, any misalignment will affect such binning and lead to spatial
      resolution loss. However, the use of 'selective' binning, consisting of the
      selection of those pixels corresponding to the interior locations of each
      element, improves resolution while preserving DQE. CONCLUSIONS: The use of high
      resolution AMFPI arrays combined with selective binning allows prototype AMFPIs
      incorporating thick, segmented scintillators to achieve imager performance
      limited only by scintillator performance. Work Supported by NIH grant R01
      CA051397.

PMID- 28517589
TI  - SU-E-J-20: Evaluation of Image Qualities and Registration of Varian KV-CBCT
      Images Reconstructed from the Reduced Number of Projections.
AB  - PURPOSE: To quantitatively investigate image qualities of the kilo-voltage cone
      beam CT images reconstructed with reduced number of projections on the Varian OBI
      system. Evaluate the registration accuracy using those CBCT images against the
      reference CT images. METHODS: CBCT images were obtained from Varian OBI system
      using standard dose head, pelvis and pelvis spotlight modes. CBCT reconstructions
      were performed with full, 1/2, 1/4, 1/6 and 1/8 of the full set of projections.
      Catphan(r) 504 phantom was used to evaluate high-contrast spatial resolution, low
      contrast visibility and uniformity. Rando phantom was imaged for rigid
      registration study. Rando was set up on the linac couch deliberately shifted by
      1cm in vertical, lateral, and longitudinal (no rotational) directions from the
      reference position. Automatch followed by manual adjustment was conducted 5 times
      to obtain the average shifts. The same method of analysis in the Rando study was
      used for the clinical registration study. One patient was imaged with pelvis mode
      and two patients were imaged with pelvis spotlight mode. RESULTS: The Catphan
      study indicates that high-contrast spatial resolution and uniformity are
      virtually not affected by the lowest projection-number (1/8) reconstruction
      scheme. However low-contrast visibility degrades when the projection number used
      for reconstruction is as low as 1/6. Rando study shows that registration accuracy
      can be achieved with images reconstructed with 1/6 of the full set of
      projections. Patient study shows similar results exhibited in Rando study.
      However, noisy images and streak artifacts are more pronounced with fewer
      projections (approximate 1/6), which decreases viewer's ability to visualize soft
      tissues in pelvic sites. CONCLUSIONS: This study shows that KV-CBCT reconstructed
      with fewer number (approximately as low as 1/6) of regular projections can be
      used for registration against the reference CT. Although the results are
      encouraging, more clinical cases should be evaluated in the future. None.

PMID- 28517590
TI  - SU-E-J-58: Patient-Specific Biomechanical Head and Neck Models for Interfraction
      Dose Accumulation.
AB  - PURPOSE: In this abstract, we discuss a biomechanical head and neck model that
      will be able to represent patient setup variations as well as physiologic changes
      and subsequently enable dose calculations on the deformed anatomy. METHODS: We
      selected Multi Pose MRI as the imaging modality to aid in model development and
      validation. The MRI data allowed us to build a biomechanically predictive model
      that will enable accurate estimation of tumor position when seeded with CT data
      alone. The soft tissue contrast and lack of ionizing radiation when using MRI
      enabled us to acquire extensive imaging datasets with a suitable variety of head
      pose variations. These poses were selected to encompass the clinical positioning
      variations so that the resulting model will accurately reflect internal organ
      motion and deformation. All images were acquired using an 8-channel, 1.5T
      research MRI system in radiology. The imaging volume extended from about T3(upper
      thoracic vertebrae) to the top of the head, thereby covering the entire head and
      neck. Model components included: muscles, skeletal bones, lymph nodes, fat
      tissues, and organs such as salivary glands, tendons, andligaments. At first, one
      MRI image dataset was selected as the reference image. The biometric properties
      (length, volume, mass, shape), hinge constraints of the bones, and the
      biomechanical properties of each of the anatomies were estimated using MRIs
      acquired at different head and neck poses. RESULTS: The model's ability to
      represent different head and neck postures can be illustrated by observing the
      internal tissue deformations andthe model's ability to represent different
      postures. CONCLUSIONS: Results show that the biomechanical model was able to
      simulate different poses that may be exhibited during interfraction patient setup
      variations and intrafraction patient motion. Future work would focus on
      integrating dose calculations on the deforming model and validating the model
      deformations.

PMID- 28517591
TI  - SU-E-J-31: Direct Point Dose Verification Using IGRT for Actual Beam Delivery.
AB  - PURPOSE: In radiation therapy, treatment planning for patients is performed using
      pre-acquired CT images. However, many patients with head-and-neck (H&N) cancer
      have tumor shrinkage and/or weight loss during their treatment course. Daily
      positional error of patients also causes unexpected deviations from the planning.
      Thus, it is essential to evaluate actual delivered dose for accurate clinical
      dosimetric consequence. In this study, actual delivered dose for an H&N site was
      determined by direct point dose measurement with metal-oxide-semiconductor field
      effect transistor (MOSFET) detectors using IGRT procedure. We experimentally
      evaluated usefulness of the IGRT procedure for accurate irradiations. METHODS:
      Treatment processes from planning to beam delivery were performed for an H&N site
      of an anthropomorphic phantom. The MOSFET detectors were fixed inside the phantom
      in advance. Then, the anthropomorphic phantom was immobilized with a mould and
      mask and scanned by simulation-CT. Beam irradiation condition was field size of
      12 cm * 12 cm, gantry angle of 0 degrees , 90 degrees  and 330 degrees , and 6 MV
      X-ray. Dose distribution was calculated with superposition algorithm with 2 mm
      calculation grid. Before the dose measurement, the anthropomorphic phantom was
      positioned using a localization system of mega-voltage cone-beam CT (MVCBCT). The
      MOSFET detectors were exposed five times according to a treatment plan. Measured
      doses with the MOSFET detectors were compared with calculated doses. RESULTS:
      Using the MVCBCT, the set-up of the anthropomorphic phantom was achieved within 1
      mm in all directions of anterior/posterior, left/right, and superior/inferior.
      The calculated doses agreed well to the measured doses within +/-3% even in
      evaluated region with high dose gradient. CONCLUSIONS: The actual delivered dose
      for an H&N site of an anthropomorphic phantom was evaluated experimentally with
      the MOSFET detectors. The IGRT procedure was useful for accurate irradiations.

PMID- 28517592
TI  - SU-E-J-03: Positioning Errors of Metal Localization Devices with Motion Artifacts
      on KV and MV Cone Beam CT.
AB  - PURPOSE: To investigate motion artifacts of kV CBCT and MV CBCT images on metal
      localization devices for image guided radiation therapy. METHODS: 8 MU pelvis
      CBCT template for Siemens Artiste MVision and Pelvis template for Varian IX on
      board Exact Arms kV were used to acquire CBCT images in this study. Images from
      both CBCT modalities were compared in CNRs, metal landmark absolute positions,
      and image volume distortion on three different planes of view. The images were
      taken on a breathing-simulated thoracic phantom in which several typical metal
      localization devices were implanted, including clips and wires for breast
      patients, gold seeds for prostate patients, and BBs as skin marks. To magnify the
      artifacts, a 4cm diameter metal ball was also implanted in the thoracic phantom
      to mimic the metal artifacts. The amplitude of the sinusoidal breathing was 1cm,
      and the period varies from 2sec, 4sec to 8sec. RESULTS: For MV CBCT, the CNR at
      4sec breathing cycle with 1cm breathing amplitude was 5.0, 3.4 and 4.6 for clips,
      gold seeds and BBs, respectively while it was 1.5, 2.0 and 1.6 for kV CBCT. On
      the images, kV CBCT showed symmetric streaking artifacts both in the transverse
      and longitudinal directions relative to the motion direction. kV CBCT images
      predicted 89% of the expected volume, while MV CBCT images predicted 95% of the
      expected volume. Simulated soft tissue observed in MVCT cannot be detected in
      kVCT. CONCLUSIONS: MV CBCT images showed better volume prediction, less streaking
      effects and better CNRs of a moving metal target, i.e. clips, BBs, gold seeds and
      metal balls than kV CBCT images. MV CBCT was more advantageous compared to kV
      CBCT with less motion artifacts for metal localization devices.

PMID- 28517593
TI  - SU-E-J-40: Lung Lesion Tracking Using Fixed-Spaced Non-Migrating Fiducial Markers
      in Robotic Radiosurgery.
AB  - PURPOSE: With lung lesion treatment being a major indication of the use of the
      CyberKnife (CK) robotic radiosurgery system (Accuray Inc, Sunnyvale, CA), the
      ability for the CK's stereoscopic kV imaging system to accurately track implanted
      fiducial markers becomes vital in the accurate delivery of therapeutic radiation.
      This study examines a novel fixed-space fiducial marker delivery system which is
      capable of delivering two VISICOIL (IBA Dosimetry America, Memphis, TN) non
      migrating fiducial markers simultaneously at a fixed spacing through a single 20
      gauge needle. More specifically, presented herein is a preliminary study which
      tests the CK'streatment localization system's (TLS) ability to track markers of
      varying size and spacing, comparing subsequent stereoscopic kV imaging to DRR's
      generated during the planning stages. METHODS: Three markers were placed in an
      XLT Lung Phantom (CIRS Inc, Norfolk, VA); two markers inserted along a diagonal
      line in a coronal plane, separated by biocompatible spacersof varying size, and a
      common third marker being placed in a non-varyinglocation in a coronal plane
      anterior to the marker pair. This third marker allows the calculation of
      rotational and translation corrections. Differentcombinations were scanned,
      planned, and simulated; 3.5mm- and 5.0mm- long markers, each 5mm in diameter,
      were separated by 15mm, 17mm, and 20mm spacers. RESULTS: The TLS system was able
      to track each of the aforementioned configurations with standard lung imaging
      parameters.Longer markers were not included in the study since earlier studies
      showed that without the natural deformation that would occur upon implantation,
      the length would induce false tracking. CONCLUSIONS: This is a necessary
      firststep in determining the minimum spacing with which the CK's TLS can track, a
      study which can now proceed with the use of phantom treatments elivered to
      orthogonally-overlapping radiochromic film, bisecting a tumor volume which is
      implanted with this fiducial marker system. Research supported in-part by IBA
      Dosimetry America.

PMID- 28517594
TI  - SU-E-J-13: A Study to Establish the Effect of CBCT Image Rotational Displacement
      on IGRT and ART Lung SBRT Treatments.
AB  - PURPOSE: To determine whether the accuracy of CBCT based IGRT and ART lung SBRT
      treatments may require extra quality assurance (QA) steps. METHODS: During CBCT
      Rando phantom acquisition we detected an unexpected ~2 degrees  image rotation
      when comparing the CW and CCW acquired scans. Misregistered angular coordinates
      may Result in a rotated reconstructed image and the target localization may lead
      to an under- or over-dosage of the target volume (TV) and organs at risk (OARs).
      The effect of image rotation on CBCT-guided lung SBRT was retrospectively
      examined in a group of six patients treated at our institution. Patient CT sets
      were rotated by 1,2, and 3 degrees . Treatment plans were recalculated using
      these rotated images to examine changes of dose-volume histogram indicators for
      IGRT and ART guided treatments. C++ simulations were run to evaluate the effect
      of CBCT image rotation. RESULTS: We determined through mathematical analysis that
      the dose coverage of the TV is dependent on its shape, location and orientation
      relative to isocenter. Dosimetric evaluation of lung SBRT patients showed that
      even for 1< N2 <3 degrees , changes in D95 to the PTV were from 2.3 +/- 2.1 to
      11.5 +/- 3.9% for IGRT and from 8.5 +/- 8.4 to 16.6 +/- 8.0% for ART. Significant
      changes were also detected at critical structure level. CONCLUSIONS: When IGRT
      and ART are employed for lung SBRT treatments, significant dosimetric changes may
      Result from the rotation of CBCT image data sets. The extent of alterations in
      dose indicators depends on both the shape of the TV and its relative location to
      isocenter. Based on our results, angular alignment of CBCT to <1 degrees  is
      essential in maintaining accurate dose delivery of IGRT and ART based lung SBRT
      treatments.

PMID- 28517595
TI  - SU-E-J-51: Interfractional Trend Analysis of Dose Discrepancies Based on 2D
      Portal Dosimetry.
AB  - PURPOSE: During a radiotherapy treatment course the dose delivery can be
      influenced by a number of factors, e.g. anatomical changes over time. Thiscan
      Result in discrepancies between planned and delivered dose. The electronic portal
      imaging device has been demonstrated to be valuable fortransit dosimetry
      verification. The aim of this study is to investigate theinformation that can be
      derived from 2D transit portal dosimetry by examining interfractional dose
      changes over a treatment course. METHODS AND MATERIALS: To create a trend
      overview of the interfractional changes intransit dose, the predicted portal dose
      for the different beams is compared to a measured portal dose using a ?
      EVALUATION: For each beam of the delivered fraction information is extracted from
      the ? images to differentiatesystematic from random dose delivery errors. From
      the systematic dose errors of a fraction for different projected contours,
      derived from the treatment planning contours several metrics are extracted like
      percentage pixels with ? exceeding unity. Finally the extracted metrics from each
      contour and beam are weighted with beam weight and the average andstandard
      deviation are calculated, resulting in a fraction Result. For this study, we
      analyzed 6 lung cancer patients and 20 prostate cancer patients. RESULTS: In some
      prostate cases the rectal filling was causing the dose delivery problems. For the
      lung cancer patients, anatomy changes from the diminishing atelectasis caused a
      transit dose difference and adaptations to the plan were applied. CONCLUSION: We
      have shown that from interfractional trend overview valuable information can be
      derived. However, to use this for adaptive radiotherapy, 2D transit dose
      differences with this methodshould be correlated with the 3D delivered dose, to
      define decision criteria.By optimizing these decision criteria it should be
      possible to prevent eitherover or under dosage of the tumor or OARs.

PMID- 28517596
TI  - SU-E-J-24: Image-Guidance Using Cone-Beam CT for Stereotactic Body Radiotherapy
      (SBRT) of Lung Cancer Patients: Bony Alignment or Soft Tissue Alignment?
AB  - PURPOSE: To assess the reliability of soft tissue alignment by comparing pre- and
      post-treatment cone-beam CT (CBCT) for image guidance in stereotactic body
      radiotherapy (SBRT) of lung cancers. METHODS: Our lung SBRT procedures require
      all patients undergo 4D CT scan in order to obtain patient-specific target motion
      information through reconstructed 4D data using the maximum-intensity projection
      (MIP) algorithm. The internal target volume (ITV) was outlined directly from the
      MIP images and a 3-5 mm margin expansion was then applied to the ITV to create
      the PTV. Conformal treatment planning was performed on the helical images, to
      which the MIP images were fused. Prior to each treatment, CBCT was used for image
      guidance by comparing with the simulation CT and for patient relocalization based
      on the bony anatomy. Any displacement of the patient bony structure would be
      considered as setup errors and would be corrected by couch shifts. Theoretically,
      as the PTV definition included target internal motion, no further shifts other
      than setup corrections should be made. However, it is our practice to have
      treating physicians further check target localization within the PTV. Whenever
      the shifts based on the soft-tissue alignment (that is, target alignment)
      exceeded a certain value (e.g. 5 mm), a post-treatment CBCT was carried out to
      ensure that the tissue alignment is reliable by comparing between pre- and post
      treatment CBCT. RESULTS: Pre- and post-CBCT has been performed for 7 patients so
      far who had shifts beyond 5 mm despite bony alignment. For all patients, post
      CBCT confirmed that the visualized target position was kept in the same position
      as before treatment after adjusting for soft-tissue alignment. CONCLUSIONS: For
      the patient population studied, it is shown that soft-tissue alignment is
      necessary and reliable in the lung SBRT for individual cases.

PMID- 28517597
TI  - SU-E-J-34: Influence of Prone versus Supine Patient Position on Localization with
      Image Guided Radiotherapy of Prostate Cancer.
AB  - PURPOSE: To retrospectively assess the influence of prone versus supine patient
      position on setup shifts and target margins for image guided radiotherapy (IGRT)
      of prostate cancer. METHODS: Ninety prostate cancer patients were treated at our
      institution between September 2006 and June2011 with IGRT utilizing daily
      megavoltage cone beam; 52 patients were prone receiving 1577 fractions and 38
      supine receiving 1035 fractions. Patients were setup to skin tattoos, imaged with
      megavoltage cone beam, then moved to treatment position by the alignment of three
      intraprostatic fiducials with lateral, longitudinal, and vertical shifts. The
      magnitude of the daily shift is root sum of squares of the translations. RESULTS:
      Patients positioned prone had a mean daily shift magnitude 1.4 mm greater than
      supine: 7.5 +/- 4.0 mm vs. 6.1 +/- 2.9 mm (p &ll; 0.001). The mean magnitude of
      the daily shift for prone vs. supine respectively were 3.7 +/- 3.1 mm vs. 2.6 +/-
      2.3 mm laterally, 3.5 +/- 3.0 mm vs. 3.3 +/- 2.6 mm longitudinally, and 3.9 +/-
      3.5 mm vs. 3.1 +/- 2.4 mm vertically. The percentage of daily shifts within our
      intuition's planning target volume (PTV) margin (7 mm posterior and 10 mm for all
      other directions) for prone vs. supine respectively were 97.3% vs. 99.5%
      laterally, 97.1% vs. 98.2% longitudinally, and 93.1% vs. 96.8% vertically.
      CONCLUSION: When prostate cancer patients were setup for IGRT utilizing daily
      megavoltage cone beam, the daily shifts from the skin tattoos to intraprostatic
      fiducials were greater on average if positioned prone vs.supine. Without IGRT,
      part of the prostate would be outside of the PTV for more treatments when
      positioned prone rather than supine.

PMID- 28517598
TI  - SU-E-J-07: Image Guided Radiotherapy for Prostate Cancer: To Shift Or to Re-Plan?
AB  - PURPOSE: Advanced imaging techniques have been developed to facilitate patient
      setup and target localization for advanced prostate radiotherapy. These
      techniques work well for translational, interfractional organ motion but may
      Result in poor target coverage for some cases where the effects of rotational
      motion and organ deformation are not corrected. This work investigates the
      feasibility of the use of 3D dose distributions to match the target volume to
      improve target coverage and critical structure sparing. METHODS: Fifteen
      previously treated prostate patients were selected for this retrospective study.
      Siemens CT-on-rails scans were performed before and after the IMRT treatment
      weekly. Ninety-eight post-treatment CT-on-rails scans were used to reconstruct
      the dose distributions. The isodose distributions and DVH were compared with
      those of the original plans. Target localization was also performed using the
      prescription isodose surface from the original plan to match the target volume
      and a new isocenter shift was applied in the dose reconstruction, which was
      evaluated against the original plans and the reconstructed dose distributions
      using the standard contour-based target-localization technique. RESULTS: The
      results show that for contour/anatomy matching, 7.1% of the 98 treatment
      fractions exhibit poor target coverage (Dmin<65Gy). For the rectum, 27.6%
      fractions violated our rectal criterion of V65<17% and 26.5% fractions violated
      the criterion of V40<35%. After the isocenter realignment based on 3D dose/target
      volume matching, all the fractions delivered >65Gy to the target, and the
      percentages of fractions that violated the rectal criteria (V65<17% and V40<35%)
      were reduced to 14.3% and 18.4%, respectively. CONCLUSIONS: The current IGRT
      procedure for isocenter alignment based on contour/anatomy matching is not ideal
      due to poor soft-tissue contrast, residual translational/rotational organ motion
      and organ deformation. Target localization based on 3D dose/target volume
      matching provides better target dose coverage and critical structure sparing that
      reduces the need for adaptive re-planning.

PMID- 28517599
TI  - SU-E-J-44: Dual Energy Subtraction Imaging to Improve Tumor Visibility at Oblique
      Angles.
AB  - PURPOSE: To characterize the contrast improvement of simulated tumors in an
      anthropomorphic phantom using Dual Energy (DE) subtraction with a clinical on
      board imager (OBI) at oblique angles. METHODS: An Alderson lung/chest
      anthropomorphic phantom with simulated tumors in the thoracic cavity was imaged
      using a sequential DE imaging methodology. High (120kVp) and low (60kVp) planar
      images were obtained in pairs every 100 in a full (3600) rotation using the OBI
      (Varian Medical Systems, Palo Alto, CA). Optimal mAs settings for DE component
      images were determined byvarying the x-ray exposure time, while maintaining a
      constant tube current. DE images were created to best suppress the bone
      overlaying the simulated tumors. Tumor visibility in DE images was quantified
      using the Contrast-to-Noise Ratio (CNR). The ratio of the CNR from the DE image
      relative to a single image (standard protocol) was evaluated as a function of
      gantry angle. RESULTS: CNR was improved with DE imaging by an average ratio of
      1.66 over all gantry angles. The greatest improvement occurred at gantry angles
      where the tumor was obstructed by the ribs alone. More modest improvements were
      observed where the tumor overlapped other soft tissue structures (such as the
      heart) or the dense spine, on a given projection. CONCLUSIONS: This study
      illustrates the feasibility of performing DE imaging at oblique gantry angles
      using a clinical on-board imaging system. Incorporating DE imaging into clinical
      practice may allow for verification of tumor position at oblique gantry angles,
      and may facilitate the development of markerless motion tracking techniques.
      Supported by a grant from Varian Medical Systems.

PMID- 28517600
TI  - SU-E-J-46: Use of Brainlab-ExacTrac IGRT with Dot-Decimal Electron
      Compensator(BolusECT) for Accurate Patient Positioning.
AB  - PURPOSE: To Validate Brainlab-ExacTrac IGRT with Dot-Decimal electron
      compensator(BolusECT) for accurate patient positioning. METHODS: Dot-Decimal
      electron compensators(BolusECT) are used to achieve conformal dose distributions
      and greater sparing to normal structures for cases with varying patient contours
      and treated with single electron beam.Setup for such patients is difficult to
      verify due to the small clearance between theelectron-cone and bolus. Hence
      additional verification is needed for fast setup to avoid discomfort for the
      patient. In this study we have explored theuse of Brainlab-ExacTrac IGRT system
      for such setups.A Preplan isrequired to construct the BolusECT and a post-plan is
      used for verifying the treatment plan. Before the patient is scanned again with
      BolusECT for post-plan, tungsten BBs were drilled in the Bolus at different
      depths and the holeswere filled with wax. Tungsten-BBs have high density and
      avoid high cost ofgold seeds.A wax phantom and BolusECT were scanned with BBs and
      a plan was generated. The plan was send to ExacTrac for DRR-generation.The Wax
      phantom with BolusECT was then set slightly off centered on thetreatment couch
      and the ExactTrac system was used to align the Phantom. The ExacTrac system was
      also tried on two patients for accurate setup. RESULTS: The ExactTrac system
      correctly identified the tungsten-BBs and aligned the phantom within +1mm. The
      SSD was then verified and checked with the planned SSD.The SSD was found to be
      within +0.5mm. In both patient setups the ExacTrac system gave Lateral,
      Longitudinal and Vertical Shifts within +1mm and the SSD was found to be within
      +0.3mm of the planned SSD. CONCLUSIONS: The BrainLab- ExacTrac IGRT system isan
      excellent,fast way of aligning the BolusECT. This avoids discomfort for patients
      by preventing longer setup times. Use of tungsten-BBs lowers the cost compared to
      gold seeds. Phantom verification should be performed before implementing this
      system for actual patient use. The SSDs must be verified after setup.

PMID- 28517602
TI  - SU-E-J-57: MRI-Linac (MRL) Guided Treatment for Esophageal Cancer.
AB  - For radiotherapy, oesophageal cancer is located in a difficult area. Spatial
      control of the dose distribution is difficult to achieve with current CT-based
      radiation techniques, as on CT, soft-tissue contrast is too low. Furthermore, the
      oesophagus moves and organs at risk (e.g. lung, heart, liver, spinal cord) are in
      close proximity. An 1.5 T MRI-accelerator (MRL) has sufficient soft-tissue tumour
      visualization possibilities to allow for precise real-time, online, position
      verification and for dose escalation without organ at riskoverdose. Our research
      consists of the preparatory work for the first clinical study on the MRL for
      patients with oesophageal cancer. To improve image quality and reduce the motion
      artefacts, the benefit of cardiac triggering and breath holds is evaluated on
      fifteen oesophageal patients. Results show the superb image quality of these MRI
      sequences. The use of this high quality MRI gives the possibility for non
      invasive real-time visualization andtracking of the tumour. We quantify
      oesophageal tumour motion on cineMRI. The tumour is tracked on sequential mixed
      T1/T2w images (acquisition time: 60s, temporal resolution: 0.5s, slice thickness:
      7mm) of a single coronal and sagittal slice using a Minimum Output Sum of Squared
      Error (MOSSE) adaptive correlation filter. Tumour registration within the
      individual images can typically be done at a millisecond time scale. Motion of
      oesophageal tumours can well be tracked and is highly variable between patients.
      The greatest mobility is seen in cranio-caudal direction, with amaximum peak-to
      peak amplitude of tumour movement of 24.5mm followed by the dorso-ventral and the
      medio-lateral direction. Movement seems greatest in tumours located in the lower
      part of the oesophagus. This study shows both the superb image quality for GTV
      localisation and the possibility for on-line and real time tumour tracking. The
      study opens thepossibility for tracked radiation delivery with a 1.5T MRI
      accelerator. Partial funding has been obtained by Elekta and Philips.

PMID- 28517601
TI  - SU-E-J-19: How Should CTV to PTV Margin Be Created - Analysis of Set-Up
      Uncertainties of Different Body Parts Using Daily Image Guidance.
AB  - PURPOSE: The objective for this study is to systematically evaluate how the CTV
      to PTV margin should be created to compensate for setup error as afunction of
      treatment site. METHODS: A total of 1757 setup MVCT images were analyzed using
      the registration between the MVCT and planning KVCT images. Among them, 526
      images were from patients with head and neck cancers; 342 were from thoracic
      site; 447 from upper abdomen and 442 from patients treated at pelvic region. The
      correction was shifts in 3 directions from setup with skin marks to final
      treatment position due to volumetric image registration. Registration was based
      on soft tissue anatomy when tumor was visible in both KVCT and MVCT. Otherwise,
      bony landmarks were used when tumors could not be identified. RESULTS: The
      anterior to posterior (A/P) direction requires the smallest correction for all
      body sites. The percentage of treatment with < 3mm set-up correction in A/P
      direction was 82.4%-96.0% for all disease sites. In medial to lateral direction
      (M/L), that number was 51.5%-74.7%. The largest set-up correction occurred in the
      superior to inferior (S/I) direction. As a function of the body site, 68.6% of
      head and neck patient had <3mm shift in the S/I direction. However, that number
      dropped to 41.8%a? 42.5% and 31.9% for thoracic, upper abdomen and pelvic sites
      respectively. In addition, 48.0% of pelvic tumor required >5mm shift in the S/I
      direction. For thoracic and abdominal tumors, there were still 34.9% and 30.7% of
      the treatments where >5mm shift in the S/I direction was needed. CONCLUSIONS:
      Uniform expansion margins in all directions are often used in radiation oncology
      practice. Our study showed setup error was directionally dependent. Therefore,
      non-uniform margin should be applied. Smaller margin can be used in A/P while
      larger expansion needs to be given in the S/I direction.

PMID- 28517603
TI  - SU-E-J-30: Using Shifting Planned Dose Matrix to Evaluate Daily Dose Changes for
      IMRT Prostate Treatment.
AB  - PURPOSE: Summation of daily DVH from KV-cone beam CT (KV-CBCT) to obtain a
      composite dose volume histogram (DVH) is challenging. Directly translating the
      planned dose matrix according to measured daily prostate displacements provided a
      common reference frame for a composite DVH from daily DVHs. The purpose of this
      study is to evaluate the shifting planned dose matrix method compared to the dose
      recalculation method using daily KV-CBCT. METHODS: Six patients, who received
      concurrent IMRT treatment for prostate and pelvic lymph nodes with 124 daily
      CBCTs, were selected for this study. Contours for CBCT's were transferred from
      the planning CT after soft tissue registration for prostate and bony registration
      for pelvic lymph nodes. Using the same planning beam configurations, we re
      calculated doses for these CBCTs after shifting to corrected treatment
      isocenters. The planned dose matrix translation was performed by an in-house
      program written in MATLAB and incorporated with Computational Environment for
      Radiotherapy Research (CERR) software. The corresponding daily DVH was obtained
      by shifting the planned dose matrix according to shifts of treatment iso-centers.
      To compare these two methods, selected endpoint doses for tumor targets and
      sensitive structures were extracted from DVHs. RESULTS: For prostate displacement
      less then 1.5 cm, the dose matrix shifting method resulted in 93% and 98%
      fractions within 5% differences from the recalculation method for D95 of prostate
      and pelvic lymph nodes, respectively. These numbers decreased to 58% and 71% when
      2% dose difference criterion was used. CONCLUSIONS: Allowing 5% daily dose
      difference, shifting planned dose matrix provides effective means to evaluating
      daily dose changes for concurrent IMRT treatment for prostate and pelvic lymph
      nodes. The utility of this tool is to provide a common coordinate frame to obtain
      composite dose distributions.

PMID- 28517604
TI  - SU-E-J-39: Minimizing IGRT Imaging Exposures: KV Radiograph Vs. KV-CBCT Vs. MV
      Portal Images.
AB  - PURPOSE: To compare the IGRT doses from MV, kV and CBCT images. METHODS: kV
      imaging systems integrated into Varian Trilogy and TrueBeam accelerators were
      modeled using BEAMnrc/DOSXYZnrc Monte Carlo codes and the dose to calibration
      phantoms for a variety of kV beams(kVp, bow-tie filters, etc.) were calculated.
      The doses to the same phantoms and kV beams were then measured experimentally
      using calibrated ion-chambers.The "calibrated" Monte Carlo kV beams were used to
      calculate dose to CT images of patients. Organ doses were analyzed using DVHs.
      RESULTS: The doses to the prostate are 0.015 and 2.2cGy using AP kV and MV
      images; are 0.06 and 2.3cGy using lateral kV and MV images; and, are 1.7 cGy
      using CBCT images. For head and neck images, the doses to the eye are 0.08 and
      0.001 cGy using AP and PA kV images; are 2.3 and 1.8cGy using AP and PA MV
      images; are 0.001 and 2.4cGy for lateral kV and MV images; and, are 0.2 cGy for
      CBCT images. For kV radiographs, organ doses can be further reduced, by over 30%,
      by using bow-tie filters. CBCT doses to the prostate are 1.6 and 0.9cGy for OBI
      and TrueBeam pelvis scans; a >40% dose reduction for the same image quality. For
      OBI CBCT head scans the doses to the eye and brain stem are 0.2 and 2.8cGy,
      respectively. CONCLUSIONS: Due to the low penetration of kV beams,selecting beam
      angles so that the sensitive organs are near the beam exit, and/or using bow-tie
      filters, can substantially reduce organ doses when using kV radiographs. For
      daily positioning of pediatric brain patient with a set of orthogonal kV images,
      a CBCT scan, or a set of orthogonal MV images, the doses to the eyes are 0.1,
      0.2, and 4.7 cGy, respectively.

PMID- 28517605
TI  - SU-E-J-12: Initial Clinical Experiences in Using 4D-CBCT as Image Guidance for
      Lung SBRT.
AB  - PURPOSE: The authors started to use Symmetry 4D-CBCT as image guidance for lung
      SBRT in August 2011. Here the authors present the initial clinical experiences
      with this novel image guidance technique. METHODS: In total 118 4D-CBCT scans
      have been acquired for 17 lung patients among which 15 received SBRT and the
      other 2 received hypofractionated treatments. 4D-CBCT scans are acquired with
      Elekta XVI 4.5 usingSymmetry, a procedure module in XVI that acquires 4D-CBCT,
      registers daily images to reference 3D-CT and generates shifts for patient setup.
      RESULTS: Typical thoracic 4D-CBCT scans with Symmetry take 3 minutes with a 200
      degree gantry rotation. Symmetry automatically sorts images into 10 phases based
      on automatic detection of diaphragm position. Then Symmetry generates two
      independent intensity-based registrations, one according to a pre-defined large
      volume of interest including the tumor, surrounding tissues and bony structures,
      the other only according to an expanded target volume. The registrations are
      obtained by registering each phase image to the reference image and averaging
      across all phases in a time-weighted manner. Eventually Symmetry provides users
      the freedom to pick either one of the two registrations, a compromise, or a
      manual tuning. Compared to regular 3D-CBCT, 4D-CBCT enables physicians to
      visually place the moving target in the center of PTV, greatly reducing the
      probability of missing target due to respiratory motion, thus enables possible
      reduction in PTV margin. 4D-CBCT also provides the ability to repeatedly evaluate
      the quality of ITV. It is possible that ITV does not fully cover the tumor motion
      due to a low quality 4D-CT simulation for a patient with difficulties in regular
      breathing. CONCLUSIONS: 4D-CBCT is a superior image guidance technique for lung
      SBRT treatments for its ability to visualize moving target. It provides
      physicians more confidence in tumor targeting and ability to repeatedly evaluate
      ITV quality during the treatment course.

PMID- 28517606
TI  - SU-E-J-50: Measurement of the HVL Value for the 120keV Photon Beam of the X-Ray
      Volume Imager (XVI) Using Ionization Chamber, Gafchromic Film XRQA2 and Diode.
AB  - PURPOSE: The value of Half Value Layer (HVL) is essential in quantifying the
      ability of an x-ray beam to penetrate the material being studied. This paper
      examines the use of three different types of detectors for measuring HVL of the
      120keV photon beam of the X-ray Volume Imager (XVI) cone beam CT system mounted
      on the Elekta Synergy (Crawley, UK) Linac: ionization chamber, Gafchromic film
      and diode. The effects of collimator diameters are presented and the chamber tip
      and chamber horizontalmethods are compared to investigate the source of
      variations in the measurement of HVL. METHODS: The measurements are done in free
      airboth using an ionization chamber calibrated for absolute dosimetry [University
      of Wisconsin Accredited Dosimetry Laboratory] and the Gafchromic film dosimeters
      [XR-QA2 (International Specialty Products, Wayne, NJ)]. The beam is collimated to
      the size of the detector to measure the exposed dose. The different thicknesses
      of the aluminum attenuators are added to beam to measure individual doses every
      time and repeated until the dose fell to below 50% of the initial unattenuated
      value. Dose measurements with a semiconductor diode detector [Barracuda MPD (RTI
      Electronics AB, NJ)] is also carried out. We plotted all results on a semi-log
      graph to find HVL value. RESULTS: When the measurements are made using ionization
      chamber with different collimator diameters we obtained 1.6% difference in HVL
      values. Measurements with chamber tip and horizontal methods agree with each
      other to within approximately 1.6% percentage difference. The percentage
      difference of the HVL values measured using the diode and ionization chamber is
      about 6.4% and that of using Gafchromic film and ionization chamber is about 8%
      percent. CONCLUSIONS: Gafchromic films and diodes can be used to measure HVL
      value of 120 keV photon beams. Recommendations for consistency in HVL
      measurements are provided.

PMID- 28517607
TI  - SU-E-J-23: Prostate Bed Motion Study Using Surgical Clips Based on Daily CBCT.
AB  - PURPOSE: To study prostate-bed motion after prostatectomy using the surgical
      clips as a surrogate. METHODS: On the treatment planning CT, surgical clips
      within the PTV are identified and contoured. They are also identified and
      contoured in each daily CBCT. The center of mass (COM) coordinates for each clip
      within the native reference frame of each image set of CT and CBCT are recorded.
      Each CBCT (for daily image guidance) is registered to the planning CT based on
      the pelvic bony structure. The resulted 3D transformation matrix is used to
      convert the clip coordinates in the CBCT to the planning CT reference frame.
      Difference between the converted COM coordinates and the one in planning CT is
      taken as the rigid motion of the prostate bed relative to the pelvic bony
      structure during the course of radiation therapy. The motion data are then
      analyzed using statistical error analysis and quantified by the commonly defined
      M (average over all fractions and all patients), S (stdev of averages per
      patient, the systematic motion), and s (root mean square of stdev per patient,
      the random motion). Among a large pool of patients, seven patients were selected
      for this retrospective study, each with 3 to 11 identifiable clips and 17 to 26
      CBCT sets. The total number of clips is 44 and total daily CBCT sets 160.
      RESULTS: In the (right-left, anterio-posterior, foot-head) directions, the M
      values are (0.2 mm, 0.4 mm, -0.6 mm), S (0.2, 2.5, 3.2), and s (1.7, 2.6, 2.1).
      CONCLUSIONS: Relative to the bony pelvic structure, the prostate bed motion
      characteristics are similar to that of intact prostate, as summarized in Table 2
      of Rasch et al 2005 ('Target Definition in Prostate, Head, and Neck.' Semin
      Radiat Oncol 15:136-145).

PMID- 28517608
TI  - SU-E-J-61: Multi-Criteria Optimization for IGRT Decision Processes.
AB  - PURPOSE: To develop a multi-criteria optimization framework for image guided
      radiotherapy decision processes. METHODS: An algorithm is proposed for a multi
      criteria framework for the purpose of patient setup verification decision
      processes. Optimal patient setup shifts and rotations are not always
      straightforward, particularly for deformable or moving targets of the spine,
      abdomen, thorax, breast, head and neck and limbs that change as a Result of
      treatment. The algorithm relies upon dosimetric constraints and objectives to aid
      in the patient setup and plan delivery such that the patient is positioned or the
      plan is optimized to maximize tumor dose coverage and minimize dose to organs at
      risk while allowing for daily clinical changes. A simple 1D model, a lung lesion
      are presented and a spine lesion. RESULTS: The algorithm delivers a multi
      criteria optimization framework allowing for clinical decisions to accommodate
      patient target variation which make setup decisions less straightforward. With
      dosimetric considerations, optimal patient positions and plan parameters can be
      derived. CONCLUSIONS: A multi-criteria framework is demonstrated to aid in the
      patient setup and determine the most appropriate daily position considering
      dosimetric goals. Future implementations include optimizations relying upon
      multiple plans, field parameters, and other dose metrics (TCP, NTCP, EUD, etc).

PMID- 28517609
TI  - SU-E-J-06: A Time Dependence Analysis of CBCT Image Quality and Mechanical
      Stability.
AB  - PURPOSE: To quantify the change, if any, in flexmap correction factors and image
      quality with the XVI system over a course of several years and from these
      results, assess their clinical impact. METHODS: Flexmap, a calibration procedure
      which corrects for imperfect gantry rotation for cone-beam CT reconstruction, and
      image quality tests were performed on three Elekta Synergy linacs equipped with
      XVI. Data was collected per month over three years. U and V values, corresponding
      to lateral and longitudinal shifts respectively, were acquired through the XVI
      software. Image quality parameters were obtained through CT imaging of the
      Catphan 500(r). For each reconstruction, pixel values for low density
      polyethylene (LDPE) and polystyrene materials were recorded. RESULTS: For all
      three linacs, analysis of the flexmap showed a significant change in the U factor
      for both month-to-month comparisons and comparisons between machines. The V
      correction factor exhibited a small variation month to month, and showed a
      slight, gradual increase over time (0.2 +/-0.08 mm). Image quality analysis
      showed a near consistent decrease (5-10%) in LDPE and polystyrene. Despite this
      decrease in pixel values, the ratio of the two pixel values remained constant,
      thus a similar decreasing trend in contrast was not observed. CONCLUSIONS:
      Analysis of monthly flexmap calibration showed the general monthly change in
      correction shifts and their general trend over several years. For image quality,
      our research exhibited roughly 0.5% per month decrease in pixel values of the
      Catphan(r). Our results imply that CBCT images obtained from XVI are not
      appropriate for treatment planning and despite the decrease in panel response
      over time, image quality with respect to contrast will remain within acceptable
      clinical standards. Future studies may be carried out to assess any correlation
      between image quality and XVI source strength.

PMID- 28517610
TI  - SU-E-J-43: Autotuning Imaging Parameters in X-Ray Fluoroscopic Tracking for Dose
      Savings.
AB  - PURPOSE: In fluoroscopy-guided clinical procedures that involve tracking objects
      over long treatment times, there is a need for reducing the amount of imaging
      dose delivered to the patient and the operating staff. In this study, we
      introduce a feedback metric to minimize tube current while maintaining a
      targeting precision threshold. METHOD AND MATERIALS: An acrylic sphere (1.6mm in
      diameter) was imaged at tube currents ranging from 0.5 mA to 0.9mA (1s) at a
      fixed energy of 50kVp. The images were acquired on a Varian Paxscan 4030A
      (2048*1536 pixels, 1100 mm source-to-axis distance, 1570 mm source-to-detector
      distance). A state feedback metric (tr(C)) based on the current object position
      was computed and plotted as afunction of the tube current. Next, the sphere was
      tracked using a particle filter with a bowtie filter (4.3-764mm thickness, Al) in
      the background. The tr(C) was used a by a PID controller to modulate the tube
      current in order to maintain a specified precision as the sphere traversed
      regions of varying thickness corresponding to the bowtie filter. RESULT:
      Comparison of thefeedback framework with a similar system employing fixed
      exposurereveals a dose savings of up to 43% when using an operating uncertainty
      of 194 mm2 . CONCLUSION: This work presents a relation between tr(C) and thetube
      current which can be leveraged to reduce imaging dose to patients and staff.

PMID- 28517611
TI  - SU-E-J-16: Prostate Bed Motion during Post-Prostatectomy Radiotherapy.
AB  - PURPOSE: To report the inter-fractional prostate bed motion (PBM) during post
      prostatectomy radiotherapy using cone-beam CT (CBCT). The correlations between
      PBM, anterior rectal wall and posterior bladder wall shifts were also
      investigated. METHODS: Seventy CBCT and 8 planning CT scans from 8 patients
      treated with prostate bed radiotherapy were retrospectively analyzed. For each
      CBCT-CT pair, two rigid image registrations were performed: one based on surgical
      clips and the other based on pelvic bony anatomy. Each registration gives a
      displacement vector. The difference between the two registration displacements
      represents the PBM. In addition, rectum/bladder contours on CT and CBCT scans
      were compared to identify the organ wall motion. Shifts of the anterior rectal
      wall and posterior bladder wall were assessed by averaging the slice-by-slice
      distances between contours on two image sets, measured along an anterior
      posterior line passing through the symphysis pubis. RESULTS: The prostate bed
      motion in the left-right (LR), anterior-posterior (AP) and superior-inferior (SI)
      directions was (0.1+/-0.9)mm, (0.9+/-1.6)mm, and (-0.4+/-1.9)mm, respectively.
      The derived PTV-CTV margin for LR, AP and SI motion was 3mm, 5mm, and 6mm,
      respectively. Pearson's correlation coefficients between PBM and anterior rectal
      wall (whole length) shifts, PBM and the cranial half of anterior rectal wall
      shifts, and PBM and posterior bladder wall shifts, were 0.43, 0.47, and 0.67,
      respectively. CONCLUSIONS: The magnitude of PBM relative to pelvic bony anatomy
      in all three directions was small. The correlation between average anterior
      rectal wall shifts and PBM was weak-to-moderate, which may be due to rectum
      contouring inconsistency. Possible sources for this inconsistency include: non
      uniform rectal wall motion through its length, low CBCT image contrast, and
      artifacts due to filling. Significant correlation between average posterior
      bladder wall shifts and PBM suggests bladder wall motion may also be a suitable
      surrogate for PBM in the AP direction.

PMID- 28517612
TI  - SU-E-J-54: Bone Detection in MR Images and Absorbed Dose in a Material Behind
      Bones in Radiotherapy.
AB  - PURPOSE: To determine whether bones could be localized accurately by using MR
      images only in radiotherapy treatment planning. Furthermore, to measure absorbed
      dose in a material behind different parts of the bone, and to evaluate dose
      calculation error in a pseudo-CT image by assuming a single electron density for
      the bones. METHODS: A dedicated phantom was constructed using fresh deer bones
      and gelatine. The accuracy of the bone edge location and the bone diameter in MR
      images were evaluated by comparing those in the images with the actual measures.
      The absorbed dose behind the bones was measured by a matrix detector at 6 and 15
      MV. Thedose calculation error in the bulk density pseudo-CT image was quantified
      by comparing the calculation results with those obtained in a standard CT image
      by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00,
      Elekta CMS Software). RESULTS: The examination of bone position revealed that the
      bones can be localized within a 1-mm-pixel-size in the MR images. The measured
      dose behind less than 2.5-cm-thick femur indicated that the absorbed dose behind
      the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15
      MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations
      illustrated that the bulk density pseudo-CT image used causes errors up to nearly
      2% to the dose behind the middle part, but also, the edge of the femur.
      CONCLUSIONS: This research ascertains that the bone localization is not a
      restrictive issue for radiotherapy treatment planning by using MR imageonly. The
      work indicates also that the decrease in absorbed dose is not necessarily
      dependent on the diameter of the bone. Future research shouldinvestigate the
      generation of more complex pseudo-CT images and the dosecalculations by using
      these. Supported by Elekta.

PMID- 28517614
TI  - SU-E-I-113: Alignment and Assembly of Small Field of View Pre-Clinical Images
      Taken with a Micro-Solid State X-Ray Imaging Detector.
AB  - PURPOSE: We have developed a Micro-Solid State X-ray Imaging Intensifier
      (MUSSXII) detector with an electron multiplying (EM)CCD chip which allows for an
      ultra-high pixel resolution of 8 * 8 microns. However, the EMCCD chip area of
      1004 * 1002 pixels results in an 8.032 * 8.016 mm imaging area and restricts the
      ability of the user to orient and properly image larger pre-clinical objects such
      as rat-kidney-vasculature casts. We propose a method to align and assemble images
      of such larger structures while preserving the ultra-high spatial resolution of
      the MUSSXII. METHODS: An imaging platform of negligible attenuation was attached
      to a stepper motor giving the platform free movement in the plane normal to the
      fluoroscopic x-ray beam. By alternating the detector's image acquisition and the
      stepper movement, many adjacent overlapping views of the object are acquired. The
      user then identifies the two pixel coordinates in adjacent images which represent
      the same point in space. A custom Matlab computer code uses the pixel coordinates
      to aggregate and average the input images which results in a larger field of view
      consisting of many ultra-high resolution images. RESULTS: The images were able to
      be successfully combined to form a large image while preserving the ultra-high
      resolution of the detector. In experimental tests, multiple portions of a
      mammography test object were imaged and virtually no spatial resolution
      degradation was found in the combined image. Additionally, when imaging a resin
      cast of rat-kidney-vasculature, vessels of less than 50 MUm could be viewed in
      the combined image. CONCLUSIONS: The setup and method were found to preserve the
      ultra-high resolution inherent to the MUSSXII while allowing pre-clinical imaging
      of objects larger than the detector's field of view. The large field of view was
      effective in orienting the user towards specific areas of interest in the objects
      imaged. Supported in part by: NIH Grants R01-EB008425, R01-EB002873, and an
      equipment grant from Toshiba Medical Systems Corp.

PMID- 28517615
TI  - SU-E-I-84: A Novel Approach for the Attenuation Correction of PET Data in PET/MR
      Systems.
AB  - PURPOSE: To evaluate the use of non-attenuated PET images (PET-NAC) as a means
      for the attenuation correction (AC) of PET images in PET/MR systems. METHODS: A 3
      step iterative segmentation process is proposed. The first step is used to
      segment the body contour from the NAC PET images using an active contour
      algorithm (Kass et al., Int J Comput Vision, 321-331 (1988)). The second step was
      to segment the lung region from the resultant image using an optimal thresholding
      approach (Xu et al., IEEE T Nucl Sci, 43, 331-336 (1996)). The purpose of the
      third step was to delineate parts of the heart and liver from the lung contour
      using a region growing approach since these parts were unavoidably included in
      the lung contour of the second step. Finally the attenuation coefficients of the
      bed were included based on CT images to eliminate the impact of the couch on the
      accuracy of AC. The final attenuation map was then used to AC the raw PET data
      and Result in a final PET image (PET-IAC). To assess the proposed segmentation
      approach, a phantom and six patients were scanned on a GE Discovery-RX PET/CT
      scanner. PET-IAC was then generated from PET- NAC using the proposed approach and
      compared to those of CT-AC PET (PET-CTAC). Visual inspection and SUV measurements
      between PET-IAC and the PET-CTAC for phantom and patient studies were performed
      to assess the accuracy of image quantification. RESULTS: Visual inspection showed
      a small difference between the PET-IAC and PET-CTAC. PET-IAC tumor SUVs were on
      average equal to 103+/-9% compared to the SUVs from the PET-CTAC in the phantom
      study, and 110+/-7% in the patient studies. CONCLUSIONS: Preliminary results
      suggest that PET-NAC for the AC of PET images is feasible in the clinic. Such an
      approach can potentially be an alternative method of MR-based AC in PET/MR
      imaging.

PMID- 28517613
TI  - A quantitative method to the analysis of MLC leaf position and speed based on
      EPID and EBT3 film for dynamic IMRT treatment with different types of MLC.
AB  - A quantitative method based on the electronic portal imaging system (EPID) and
      film was developed for MLC position and speed testing; this method was used for
      three MLC types (Millennium, MLCi, and Agility MLC). To determine the leaf
      position, a picket fence designed by the dynamic (DMLC) model was used. The full
      width half-maximum (FWHM) values of each gap measured by EPID and EBT3 were
      converted to the gap width using the FWHM versus nominal gap width relationship.
      The algorithm developed for the picket fence analysis was able to quantify the
      gap width, the distance between gaps, and each individual leaf position. To
      determine the leaf speed, a 0.5 * 20 cm2 MLC-defined sliding gap was applied
      across a 14 * 20 cm2 symmetry field. The linacs ran at a fixed-dose rate. The use
      of different monitor units (MUs) for this test led to different leaf speeds. The
      effect of leaf transmission was considered in a speed accuracy analysis. The
      difference between the EPID and film results for the MLC position is less than
      0.1 mm. For the three MLC types, twice the standard deviation (2 SD) is provided;
      0.2, 0.4, and 0.4 mm for gap widths of three MLC types, and 0.1, 0.2, and 0.2 mm
      for distances between gaps. The individual leaf positions deviate from the preset
      positions within 0.1 mm. The variations in the speed profiles for the EPID and
      EBT3 results are consistent, but the EPID results are slightly better than the
      film results. Different speeds were measured for each MLC type. For all three MLC
      types, speed errors increase with increasing speed. The analysis speeds deviate
      from the preset speeds within approximately 0.01 cm s-1 . This quantitative
      analysis of MLC position and speed provides an intuitive evaluation for MLC
      quality assurance (QA).

PMID- 28517616
TI  - SU-E-I-95: Multiscale Normalized Metal Artifact Reduction (MS-NMAR) in Computed
      Tomography.
AB  - PURPOSE: Medical x-ray CT devices produce images of high quality; however, the
      metal artifacts may arise from the adverse effect of metal materials present in
      the imaged objects. Conventional methods for metal artifact reduction (MAR)
      substitute the contaminated projection data corresponding to metal traces by
      specific interpolations in the projection space. Nevertheless, these methods
      usually introduce new artifacts, because the prior information of the imaged
      object (i.e., the prior image) was not involved. Therefore, a normalized MAR
      (NMAR) has further been invented, in which the projection space interpolation was
      carried out with respect to the ratio (i.e., normalization) of projection raw
      data to re-projection of the prior image. This feature renders NMAR a very high
      accuracy. However, the normalization in NMAR is more reasonable for the larger
      scale contents rather than for the smaller scale details. METHODS: The proposed
      MS-NMAR method is a generalization of NMAR with a dedicated multiscale framework.
      Both projection raw data and re-projection of the prior image ill be decomposed
      into each scale. The normalization followed by the linear interpolation is
      performed in each scale, in which the larger the scale is the wider the interval
      the linear interpolation is operated with. Composite projection data are acquired
      by summing the projection components in all scales. MS-NMAR corrected image is
      reconstructed from the composite projection data. RESULTS: Real CT data are used
      to verify the efficiency of the proposed method, and to compare with conventional
      MAR and NMAR. The quality of reconstructed image after MAR is evaluated by
      inspecting the region around the metal material. CONCLUSIONS: Both NMAR and MS
      NMAR have a better performance as compared with the conventional MAR. Meanwhile,
      MS-NMAR outperforms NMAR, considering it hinders the productions of new artifacts
      while reducing the original metal artifacts. This work is partially supported by
      the US National Institute of Health through grants P50-AG025688 and 2P50AG025688.

PMID- 28517617
TI  - SU-E-I-106: Description of Energy Dose Deposition Kernel for the Diagnostic Beam.
AB  - PURPOSE: Over the recent years, the employment of kV x-rays as a diagnostic tool
      into clinical routine has resulted in a significant increase in the patient's
      exposure to ionizing radiation. The accurate determination of the absorbed dose
      to patients during diagnosis is therefore necessary to avoid unnecessary exposure
      to the patient. This study presents an analytical model of the energy deposition
      kernel for the monoenergetic and polyenergetic kV beams for the fast calculation
      of dose in radiography. METHODS: The analytical model is based on the pencil beam
      kernels derived from Monte Carlo simulations. DOSXYZnrc code from the EGSnrc
      family was employed to simulate the pencil beam of 0.1 cm width for 80, 100 and
      120 keV mono-energetic and polyenergetic beams. The lateral dose profiles were
      calculated at different depths within a homogenous water phantom of size 50*50*50
      cm3 . The evaluated dose profiles showed a high amplitude primary component at
      the central axis and a long range low amplitude scatter component spanning a
      considerable distance from the central axis. The profiles were fitted
      analytically with a triple exponential decay function with an offset. All
      coefficients of the exponential function were further fitted with appropriate
      analytical functions to represent their behavior relative to depth and photon
      energy. The accuracy of the obtained kernel was checked by the convolution of a
      rectangular fluence profile and comparing the calculated dose distribution with
      the Monte Carlo simulated dose profiles for 2*2 cm2 field size. RESULTS AND
      CONCLUSION: In a homogeneous phantom, the comparisons of the convolution method
      and Monte Carlo simulations showed sufficient agreement except for largest depths
      (deviation approx. 15%). Future developments will focus on an implementation of
      the method for dose calculation in the patient.

PMID- 28517618
TI  - SU-E-J-02: Accuracy of Fiducial Marker Localization Using Axial and Helical CT,
      Cone-Beam CT and KV Imaging.
AB  - PURPOSE: To determine localization errors of fiducial markers using axial (ACT)
      and helical CT (HCT), cone beam CT (CBCT) and kV imaging. METHODS AND MATERIALS:
      A thorax phantom containing markers of various sizes (2.5, 5, 10, 20mm) was
      imaged using ACT, HCT, CBCT and kV imaging. The phantom was imaged with and
      without motion (15mm amplitude, 15 cycles/min). CT images were reconstructed at
      0.625, 1.25, 2.5 and 5mm thickness. Marker location and length were measured
      using axial and coronal imaging. RESULTS: The measured marker size increased
      almost linearly with increased slice thickness used in CT reconstruction with ACT
      for the stationary phantom. In HCT, the marker size varied non-linearly with
      increase in slice thickness. Motion of the phantom induced further blurring and
      shifts of the center of the marker with different sizes. The 10 mm marker was
      elongated up to 13.5 mm and 16.2 mm in the ACT and HCT, respectively. The markers
      were elongated up to nearly 26 mm using axial and helical scanning modes by
      phantom motion. The displacement of maker center was more prominent in the HCT
      with a shift up to 2 mm due to slice thickness for stationary phantom. The marker
      center was displaced by up to 18 and 22 mm using ACT and HCT, respectively, which
      was even higher than 15 mm motion amplitude. KV imaging produced the sharpest
      marker image with the least difference between actual and measured marker sizes.
      CONCLUSION: Increase in slice thickness enlarged the apparent marker size and
      displaced the maker center in ACT and HCT. Motion led to further enlargement in
      the maker size and displacement of maker center that depended on the motion
      amplitude. These effects should be considered in CT-based image-guided radiation
      therapy to ensure accurate tumor localization and patient positioning with
      implanted markers.

PMID- 28517619
TI  - SU-E-I-88: Realistic Pathological Simulations of the NCAT and Zubal
      Anthropomorphic Models, Based on Clinical PET/CT Data.
AB  - PURPOSE: In the present study a patient-specific dataset of realistic PET
      simulations was created, taking into account the variability of clinical oncology
      data. Tumor variability was tested in the simulated results. A comparison of the
      produced simulated data was performed to clinical PET/CT data, for the validation
      and the evaluation of the procedure. METHODS: Clinical PET/CT data of oncology
      patients were used as the basis of the simulated variability inserting patient
      specific characteristics in the NCAT and the Zubal anthropomorphic phantoms. GATE
      Monte Carlo toolkit was used for simulating a commercial PET scanner. The
      standard computational anthropomorphic phantoms were adapted to the CT data
      (organ shapes), using a fitting algorithm. The activity map was derived from PET
      images. Patient tumors were segmented and inserted in the phantom, using
      different activity distributions. RESULTS: The produced simulated data were
      reconstructed using the STIR opensource software and compared to the original
      clinical ones. The accuracy of the procedure was tested in four different
      oncology cases. Each pathological situation was illustrated simulating a) a
      healthy body, b) insertion of the clinical tumor with homogenous activity, and c)
      insertion of the clinical tumor with variable activity (voxel-by-voxel) based on
      the clinical PET data. The accuracy of the presented dataset was compared to the
      original PET/CT data. Partial Volume Correction (PVC) was also applied in the
      simulated data. CONCLUSIONS: In this study patient-specific characteristics were
      used in computational anthropomorphic models for simulating realistic
      pathological patients. Voxel-by-voxel activity distribution with PVC within the
      tumor gives the most accurate results. Radiotherapy applications can utilize the
      benefits of the accurate realistic imaging simulations, using the anatomicaland
      biological information of each patient. Further work will incorporate the
      development of analytical anthropomorphic models with motion and cardiac
      correction, combined with pathological patients to achieve high accuracy in tumor
      imaging. This research was supported by the Joint Research and Technology Program
      between Greece and France; 2009-2011 (protocol ID: 09FR103).

PMID- 28517620
TI  - SU-E-I-99: An Ultra-High Resolution Small Field-Of-View Solid State X-Ray Imaging
      Detector Based on an Electron Multiplying CCD.
AB  - PURPOSE: To demonstrate the ultra-high resolution capability of a small field-of
      view (FOV) solid state x-ray imaging detector based on an EMCCD sensor. METHODS:
      A micro-solid state x-ray image intensifier (micro-SSXII) was developed to serve
      as an ultra-high resolution region-of-interest (ROI) imaging detector. It is
      based on an 8 micron, 1004 by 1002 pixel electron multiplying CCD (EMCCD)
      optically coupled to a 100 micron thick CsI(Tl) phosphor through a fiber optic
      window resulting in a FOV of 8 mm. The modulation transfer function (MTF) of the
      micro-SSXII was measured by the slanted edge method. A cast of a rat kidney (made
      by mixing resin and iodine for contrast) and a mammography line pair test object
      were imaged at 50 kVp to demonstrate the detector's ultra-high resolution
      capability visually. RESULTS: The MTF was determined and was 5% at 20 cycles/mm.
      This is consistent with the clear visualization of the maximum 20 lp/mm group in
      the image of the mammography test object. Also, iodine bubbles with diameters as
      small as 25 microns, which are formed by the non-uniform mixing of the iodine in
      the resin cast, can be clearly identified in the rat kidney vessels. CONCLUSIONS:
      The ultra-high resolution capability (>20 lp/mm) but small FOV (8 mm) of the
      micro-SSXII in combination with a low-energy x-ray source may have application
      for investigations of vascular specimen details and other fine structures where
      optical or other surface imagers would be unsuited for evaluating features below
      the surface. Contact radiography with this imager combined with a large higher
      load focal spot x-ray tube may be a promising substitute for magnification
      radiography which is limited by the use of specialized low output microfocus x
      ray tubes and geometric un-sharpness for large magnifications. Supported in part
      by: NIH Grants R01-EB008425, R01-EB002873 and an equipment grant from Toshiba
      Medical Systems Corp.

PMID- 28517621
TI  - SU-E-I-66: Is T2 Individual Correction in MRS for Fat Quantification Tool
      Necessary?
AB  - PURPOSE: In nonalcoholic steatohepatitis (NASH) the fat quantification is
      necessary. One of the most used in vivo quantification method is the magnetic
      resonance spectroscopy (MRS). It is well known the importance of T2 correction to
      improve the accuracy and precision of this method; however the T2 measurements
      require time consumption. In this work we estimated the T2 values for water and
      fat in NASH patient with different fat contents in order to verify if a generic
      T2 correction is adequate for fat quantification in the clinical routine.
      METHODS: 19 NASH patients (48+/-10 years, 9 female) underwent MR procedure
      several times. Imaging was performed on a 3.0T clinical MRI scanner using a 3P
      Dixon method. MRS data was acquired using single voxel (3*3*3 cm) PRESS
      acquisition (TR=1500ms, 1024points, 2 KHz bandwidth). The PRESS acquisition was
      performed in a single TE (60 ms, 32 averages) and multiple TE (32,45,80 and 135
      ms; 16 averages). The software jMRUI was used for peak quantification. The MRS
      results were T2 corrected using generic values (T2fat=55ms and T2water=25 ms) for
      single TE data and individual values estimated from multi-TE data before fat
      fraction calculation. A linear correlation was estimated between the fat fraction
      obtained using 3P-Dixon and the spectroscopy methods. RESULTS: The T2 values
      estimated were 69+/-14 and 27+/-3 ms for fat and water, respectively. The
      correlation coefficients between 3P-Dixon and the spectroscopy methods were: 0.75
      for MRS-individual and 0.82 for MRS-general. CONCLUSIONS: The procedure using a
      generic T2 value was more correlated to Dixon than one using individual values,
      suggesting that is more important a good signal-to-noise ratio than a very
      precise T2 value for correction. The reduced range of T2water values doesn't
      reflect any considerable iron deposition in NASH patients. In diseases with low
      iron deposition it's not necessary the individual T2 correction for fat
      quantification from MRS data.

PMID- 28517622
TI  - SU-E-I-110: Minimized Pediatric Dose in Direct Radiography (DR).
AB  - PURPOSE: Pediatric x-rays techniques are not standardized. They depend upon:
      patient size, anatomical localized and equipment manufacturers. Most pediatric
      techniques use the default factory settings. This project's goal is to find the
      best compromise between dose to pediatric patients and optimal image quality.
      METHODS: Low contrast discrimination is the key to image quality. The
      manufacturers (Philips and GE) specific techniques were used to establish
      baseline values. The following factors were evaluated: kVp, mA, time, use of
      grid, collimation, focal spot size, AEC/manual, and added filters. The entrance
      skin exposure, entrance exposure to detector, equipment exposure index (EI) and
      contrast to noise ratio (CNR) for different thickness from neonatal to average
      child were assessed. RESULTS: Overall, some manufacturer's specific pediatric
      exposures techniques have higher entrance skin exposure than typical specified
      techniques. Equipment reported exposure index are not accurate enough to be used
      as 'dosimeter'. Lower kVp, mA with longer exposure time will increase the low
      contrast detectability with better CNR but these also change the entrance skin
      exposure. Removal of grid, filters do reduce the entrance skin exposure, but
      these also reduce low contrast detectability. Focal spot size does not make a big
      impact in image quality due to the average detector pixel size. Collimation does
      make a difference in AEC sensitivity and exposure index (EI). CONCLUSIONS: There
      is no single technique that is the best technique. It is all depend upon many
      factors like exam type and the size of the patients. Moreover, it is difficult to
      program the generator to use low kVp techniques, add or remove of filters,
      collimation, and use of AEC or manual mode, grid on or off in order to optimize
      the image quality while minimizing the dose to the patients. Some pediatric
      techniques with their associate CNR and radiation dose will be presented.

PMID- 28517623
TI  - SU-E-I-76: Optimizing Imaging Parameters for a Novel Radiographic Imaging System
      for the Detection of Corrosion in Aluminum Aircraft Structures.
AB  - PURPOSE: A laboratory-based phase-contrast radiography/tomosynthesis imaging
      system previously (Med. Phys. Vol. 38, 2353 May 2011) for improved detection of
      low-contrast soft-tissue masses was used to evaluate the sensitivity for
      detecting the presence of thin layers of corrosion on aluminum aircraft
      structures. METHODS: The evaluation utilized a test object of aluminum (2.5 inch
      * 2.5 inch * 1/8 inch) on which different geometric patterns of 0.0038 inch thick
      anodized aluminum oxide was deposited. A circular area of radius 1 inch centered
      on the phantom's midpoint was milled to an approximate thickness of 0.022 inches.
      The x-ray source used for this investigation was a dual focal spot, tungsten
      anode x-ray tube. The focal used during the investigation has a nominal size of
      0.010 mm. The active area of the imager is 17.1 cm * 23.9 cm (2016 * 2816 pixels)
      with a pixel pitch of 0.085 mm. X-ray tube voltages ranged from 20-40 kVp and
      source- to-object and object-to-image distances were varied from 20-100 cm.
      Performance of the phase-contrast mode was compared to conventional absorption
      based radiography using contrast ratio and contrast-to-noise ratios (C/N). Phase
      contrast performance was based on edge-enhancement index (EEI) and the edge
      enhancement-to-noise (EE/N) ratio. RESULTS: for absorption-based radiography, the
      best C/N ratio was observed at the lowest kVp value (20 kVp). The optimum
      sampling angle for tomosynthesis was +/- 8 degrees. CONCLUSIONS: Comparing C/N to
      EE/N demonstrated the phase-contrast techniques improve the conspicuity of the
      oxide layer edges. This work provides the optimal parameters that a radiographic
      imaging system would need to differentiate the two different compounds of
      aluminum. Subcontractee from Positron Systems Inc. (Boise, Idaho) through United
      States Air Force grant (AF083-225).

PMID- 28517624
TI  - SU-E-I-92: Accuracy Evaluation of Depth Data in Microsoft Kinect.
AB  - PURPOSE: Microsoft Kinect has potential for use in real-time patient position
      monitoring in diagnostic radiology and radiotherapy. We evaluated the accuracy of
      depth image data and the device-to-device variation in various conditions
      simulating clinical applications in a hospital. METHODS: Kinect sensor consists
      of infrared-ray depth camera and RGB camera. We developed a computer program
      using OpenNI and OpenCV for measuring quantitative distance data. The program
      displays depth image obtained from Kinect sensor on the screen, and the cartesian
      coordinates at an arbitrary point selected by mouse-clicking can be measured. A
      rectangular box without luster (300 * 198 * 50 mm3 ) was used as a measuring
      object. The object was placed on the floor at various distances ranging from 0 to
      400 cm in increments of 10 cm from the sensor, and depth data were measured for
      10 points on the planar surface of the box. The measured distance data were
      calibrated by using the least square method. The device-to-device variations were
      evaluated using five Kinect sensors. RESULTS: There was almost linear
      relationship between true and measured values. Kinect sensor was unable to
      measure at a distance of less than 50 cm from the sensor. It was found that
      distance data calibration was necessary for each sensor. The device-to-device
      variation error for five Kinect sensors was within 0.46% at the distance range
      from 50 cm to 2 m from the sensor. The maximum deviation of the distance data
      after calibration was 1.1 mm at a distance from 50 to 150 cm. The overall average
      error of five Kinect sensors was 0.18 mm at a distance range of 50 to 150 cm.
      CONCLUSIONS: Kinect sensor has distance accuracy of about 1 mm if each device is
      properly calibrated. This sensor will be useable for positioning of patients in
      diagnostic radiology and radiotherapy.

PMID- 28517625
TI  - SU-E-I-59: Investigation of the Usefulness of a Standard Deviation and Mammary
      Gland Density as Indexes for Mammogram Classification.
AB  - PURPOSE: To investigate the usefulness of the standard deviation of pixel values
      in a whole mammary glands region and the percentage of a high- density mammary
      glands region to a whole mammary glands region as features for classification of
      mammograms into four categories based on the ACR BI-RADS breast composition.
      METHODS: We used 36 digital mediolateral oblique view mammograms (18 patients)
      approved by our IRB. These images were classified into the four categories of
      breast compositions by an experienced breast radiologist and the results of the
      classification were regarded as a gold standard. First, a whole mammary region in
      a breast was divided into two regions such as a high-density mammary glands
      region and a low/iso-density mammary glands region by using a threshold value
      that was obtained from the pixel values corresponding to a pectoral muscle
      region. Then the percentage of a high-density mammary glands region to a whole
      mammary glands region was calculated. In addition, as a new method, the standard
      deviation of pixel values in a whole mammary glands region was calculated as an
      index based on the intermingling of mammary glands and fats. Finally, all
      mammograms were classified by using the combination of the percentage of a high
      density mammary glands region and the standard deviation of each image. RESULTS:
      The agreement rates of the classification between our proposed method and gold
      standard was 86% (31/36). This result signified that our method has the potential
      to classify mammograms. CONCLUSIONS: The combination of the standard deviation of
      pixel values in a whole mammary glands region and the percentage of a high
      density mammary glands region to a whole mammary glands region was available as
      features to classify mammograms based on the ACR BI- RADS breast composition.

PMID- 28517626
TI  - SU-E-I-70: Semi-Automatic, User-Driven Breast, Chest Wall and FGT Segmentations
      Based on Hough Transform, Morphology Tools and Histogram Technology.
AB  - PURPOSE: Preliminary analysis shows that breast fibroglandular tissue (FGT) ratio
      and background parenchymal enhancement (BPE) of magnetic resonance (MR) imaging
      are predictive of future breast cancer risk. Adequate methods for automatic/semi
      automatic breast and chest wall segmentation, and FGT histogram extraction and
      analysis were not available. METHODS: This method is tested on the retrospective
      HIPAA-compliant study, which includes 1275 women who underwent breast MR imaging
      between December 2002 and February 2008. The method works in user-directed stages
      for each image slice: 1. A straight-line and ellipse Hough transform are applied
      to detect chest wall boundaries and separate out the chest region if it is
      present. 2. Edge detection and morphology tools are deployed to segment out the
      breast region. Human input is required to justify and adjust the segmentation
      result. 3. Typical breast MRI histograms have double peaks, of fat regions and
      FGT content inside the segmented breast. Human input is needed here to justify
      and select a proper segmentation threshold value for whole breast FGT
      segmentation. Interactive GUIs were developed in Matlab for all the human input
      sections. RESULTS: Various chest wall boundary lines are detected by Hough
      transform. Breast region is segmented out either automatically by the morphology
      tools or redefined by researchers if there is no proper boundaries available in
      the MR images. Breast region is analyzed by histogram technology to separate FGT
      from fat. CONCLUSIONS: We have developed a semi-automatic human-guided breast
      segmentation method for MRI based on Hough transform, morphology tools and
      histogram technology. This approach enables novel breast segmentation and
      analysis.

PMID- 28517627
TI  - SU-E-I-80: Optimizing Scanning-Beam Digital X-Ray Tomosynthesis of the Lungs.
AB  - PURPOSE: We propose to optimize the geometry of the Scanning-Beam Digital
      Tomography system (SBDX) for application to lung tumor biopsies, thereby
      providing real-time 3D tomographic reconstructions for target verification. The
      unique geometry of the system requires trade-offs between patient dose, imaging
      field of view and tomosynthesis angle. METHODS: We used PCXMC, a Monte Carlo
      simulation software package, to determine the dose to organs of interest as well
      as the Average body dose and Effective Dose (both ICRP 60 and 103) for source to
      detector distances (SDDs) between 90cm and 150cm. To facilitate modeling our
      system, a modified version of PCXMC was created. We also used matlab to evaluate
      the possible tomosynthetic angles that Result across the field of view for the
      same SDDs. RESULTS: To maximize the tomosynthesis angle while leaving space for
      the patient, an SDD of between 90cm and 110cm is appropriate. At SDD 100cm,
      patient centered at 40 cm from the detector, operated in fluoro mode, the SBDX
      system delivers ~0.38x the dose of a normal mobile fluoroscopy system operating
      at 30 fps. Because of the inverse geometry of the system, the dose to the patient
      goes up as the patient gets closer to the detector. Tomosynthetic angles up to 15
      degrees over a 5-cm field-of-view can be achieved for this geometry. The patient
      must be placed within 45cm of the detector in order to achieve the benefits from
      reduced SDD and increased tomosynthetic angle. CONCLUSIONS: The dose-rate for our
      optimized geometry is acceptable, although higher dose rates for improved nodule
      visualization may be required. Additional dose optimization steps include
      modifying the scanning beam pattern to optimize for tomosynthetic image
      acquisition. Overall dose during the biopsy procedure will likely decrease since
      nodule targeting will be improved and the overall number of biopsies required
      will be reduced. This work has received funding from NIH grant R21 HL098683, as
      well as from the Lucas Foundation.

PMID- 28517628
TI  - SU-E-I-63: Performance Study of An Electron-Tracking Compton Camera for Medical
      Imaging.
AB  - PURPOSE: Conventional gamma-ray detector, PET and SPECT, have the limitation of
      energy and field of view. These limitations are major problems of studying for a
      new medical imaging. Therefore, we have developed the new imaging detector which
      is an electron-tracking Compton camera (ETCC). METHODS: A reconstruction method
      of Compton camera (CC) is using the physics principle. Because of using physics
      principle, CC can have a wide energy dynamic range and wide field of view.
      Conventional CC, however, cannot catch Compton recoil electron tracks, and this
      is one of the reasons of low imaging power. We have developed a time projection
      chamber (TPC) using micro pixel chamber (MUPIC) as the new detector for ETCC. The
      MUPIC is 2-dimensional gaseous detector and this position resolution is less than
      400 MUm. Using this detector, ETCC can get electron tracks which are generated
      from Compton scattering. In this paper, we show the prototype ETCC performance
      and imaging results. RESULTS: ETCC achieved a wide energy dynamic range (200
      1300keV) and wide field of view (3 steradian). Also we succeeded in imaging new
      imaging reagents using mice as follows; (1) F-18-FDG (511 keV) and I-131-MIBG
      (364 keV) simultaneous imaging for double clinical tracer imaging, (2) Zn-65-
      porphyrin (1116 keV) imaging for high energy gamma-ray imaging and, (3) imaging
      of some minerals (Mn-54, Zn-65) in mice and so on. And we succeeded in 3-D
      imaging which has imaged only one direction using one head camera. CONCLUSIONS:
      We have developed the ETCC for new medical imaging device and succeeded in
      imaging the some imaging reagents. We started to develop the new ETCC which can
      image the mouse within 30 min. Thus, this detector has the possibility of new
      medical imaging.

PMID- 28517629
TI  - SU-E-I-83: Detectability Limits of a New Positron Emission Mammography in
      Relation to Tumour-Size, Tumour-To-Background Ratio and Activity Concentration.
AB  - PURPOSE: Positron emission mammography (PEM) improves spatial resolution and
      sensitivity, making it suitable for early breast tumours detection. The aim of
      this study is to evaluate the limits of a dedicated breast PET in terms of tumour
      size, tumour-to-background activity concentration ratio (TBR) and activity
      concentration. METHODS: A dedicated PEM is evaluated. To characterize the device,
      we use a phantom of 15 cm of diameter containing 6 inserts of inner diameters 18,
      15, 11, 8, 5 and 3 mm. To evaluate the detectability limits images are acquired
      by varying the TBR from 10 to 2 and without background activity concentration. In
      all the studies the activity concentration for the 6 inserts is the same (3.7
      kBq/ml). To asses the activity concentration limit, the SBR is maintained fixed
      and acquisitions at different times are performed. RESULTS: When there is not
      background, all the inserts are visible in the PEM. Increasing the background
      decreases the detectability. With a SBR of 10, the smaller insert is still
      visible. For TBR between 10, inserts >= 5 mm can be seen With a TBR of 2, only
      inserts with a diameter higher than 5 mm are visible. When the TBR is fixed,
      decreasing the activity concentration, decreases the capability of detectability.
      CONCLUSIONS: The results suggest that PEM can be used for diagnosis of small
      lesions when TBR is higher than 2. Further clinical studies need to be carried
      out in order to validate these results.

PMID- 28517630
TI  - SU-E-I-94: External Beam Radiation Cherenkov Emission in Tissue Used for Tissue
      Oxygen Sensing.
AB  - PURPOSE: To show that Cherenkov emission is generated by external radiotherapy
      beam in tissue, and could serve as optical source to excite an oxygen sensitive
      phosphor, Oxyphor G4, within tissue. The intensity and lifetime of the
      phosphorescence was measured with a time-gated system and reveals the oxygenation
      levels in the tissue phantom. METHODS: A tissue phantom made with PBS, 1% v/v
      Intralipid-20% (Sigma Aldrich), 1% v/v whole blood and Oxyphor G4 in 1 MUM
      concentration is irradiated by 18MeV external radiotherapy electron beam at a
      dose rate of 4 Gy/min generated by a medical linear accelerator (Varian LINAC
      2100C, Varian Medical Systems). On one side of the phantom, a fiber bundle is
      used to conduct optical signal to a spectrometer connected to a fast gating ICCD
      (PI-MAX3, Princeton Instruments). For each oxygenation level, a series of
      spectrum of phosphorescence at different time points is measured by the time
      domain gating technique. Lifetime of phosphorescence is analyzed by exponential
      fitting and is validated by comparison to an independent analysis by frequency
      domain phosphorimetry. Monte Carlo simulations using GEANT4, of the fiber optic
      collection of Cerenkov light were performed to decide the sensitivity of the
      optical system for a range of specified geometries and beam types. Simulation
      results identify the effective depth within the phantom that is sampled by the
      optical collection of the Cerenkov signal. RESULTS: Simulations show that we can
      detect the Cherenkov signals comes from an approximately 5 mm depth from within
      the tissue phantom. Lifetime of the phosphorescence and pO2 of the phantom could
      be measured and calculated correctly by the time domain gating system.
      CONCLUSIONS: This work indicates time domain gating techniques combined with an
      oxygen sensitive phosphor are capable of accurately monitoring tissue oxygenation
      from a reasonable sampling depth in tissue in vivo during external beam
      radiotherapy. NIH grant R01CA109558.

PMID- 28517631
TI  - SU-E-I-105: Optimizing Bomb Squad X-Ray Systems for Incidental Human Exposures.
AB  - PURPOSE: A current terrorist tactic involves strapping an explosive device to a
      live victim. Technicians wishing to x-ray the device need to use appropriate
      exposures to create clear images while mitigating incidental health problems for
      the live victim. This project involves characterizing and optimizing a popular
      radiographic system in the explosive investigation community, both for general
      use and, more specifically, for generating x-rays with a human subject in the
      beam path. This project seeks to minimize the dose to a victim incidentally
      located in the beam path, while maximizing image quality, thereby allowing
      appropriate image evaluation to neutralize the explosive threat. METHODS: Image
      quality and dose optimization begins with characterization of the x-ray source.
      The source in this study is an XRS-3, a portable device developed by Golden
      Engineering, which nominally produces a 270 kVp beam. Characterization of the
      beam involves verifying the actual kVp, as well as determining the average energy
      of the beam with various amounts of filtration added to the beam path. The kVp
      was verified using a noninvasive technique, utilizing the measurement of the dose
      attenuation through lead and then modeling the energy dependent attenuation curve
      of the lead using specific mass attenuation coefficients and parameters suggested
      by Joseph (Joseph, P.M., Med. Phys. Vol. 2, July/Aug1975; 201-207) in order to
      calculate the kVp through linear regression. RESULTS: The average energy of an
      unfiltered beam was 52 keV, and increases through adding various combinations of
      Cu and brass filters to a maximum value of 121 keV with 3 mm copper + 3 mm brass
      filtration. The calculated kVp was 290 kV. CONCLUSIONS: The average energies
      using filtration fall within the diagnostic range. The kVp fits well within the
      manufacturer's specifications of 15% deviation. Optimization can be accomplished
      with these parameters. University of Oklahoma Health Sciences Center- Department
      of Radiological Sciences.

PMID- 28517632
TI  - SU-E-J-01: Analysis of Acquisition Parameters That Caused Artifacts in Four
      Dimensional (4D) CT Images of Targets Undergoing Regular Motion.
AB  - PURPOSE: The aim of this study was to clarify the impacts of acquisition
      parameters on artifacts in four-dimensional computed tomography (4D CT) images,
      such as the partial volume effect (PVE), partial projection effect (PPE), and mis
      matching of initial motion phases between adjacent beds (MMimph) in cine mode
      scanning. METHODS: A thoracic phantom and two cylindrical phantoms (2 cm diameter
      and heights of 0.5 cm for No. 1 and 10 cm for No.2) were scanned using 4D CT. For
      the thoracic phantom, acquisition was started automatically in the first scan
      with 5 sec and 8 sec of gantry rotation, thereby allowing a different phase at
      the initial projection of each bed. In the second scan, the initial projection at
      each bed was manually synchronized with the inhalation phase to minimize the
      MMimph. The third scan was intentionally un-synchronized with the inhalation
      phase. In the cylindrical phantom scan, one bed (2 cm) and three beds (6 cm) were
      used for 2 and 6 sec motion periods. Measured target volume to true volume ratios
      (MsTrueV) were computed. The relationships among MMimph, MsTrueV, and velocity
      were investigated. RESULTS: In the thoracic phantom, shorter gantry rotation
      provided more precise volume and was highly correlated with velocity when MMimph
      was minimal. MMimph reduced the correlation. For moving cylinder No. 1, MsTrueV
      was correlated with velocity, but the larger MMimph for 2 sec of motion removed
      the correlation. The volume of No. 2 was similar to the static volume due to the
      small PVE, PPE, and MMimph. CONCLUSIONS: Smaller target velocity and faster
      gantry rotation resulted in a more accurate volume description. The MMimph was
      the main parameter weakening the correlation between MsTrueV and velocity.
      Without reducing the MMimph, controlling target velocity and gantry rotation will
      not guarantee accurate image presentation given current 4D CT technology.

PMID- 28517633
TI  - SU-E-I-87: Tumor Positioning for PET-CT Scanner by Jointly Registration and
      Segmentation.
AB  - PURPOSE: In order to achieve tumor positioning for radiotherapy planning
      automatically and accurately, an efficient tumor positioning method is proposed
      by jointly registration and segmentation for 18F-FDG PET-CT scans. METHODS: At
      the first stage, the tumor is segmented from PET scans by region growing using
      the manual seeds which employs the SUV monotonous features, and then the tumor
      contours are transferred to corresponding CT images automatically for following
      radiation therapy planning by a new deformable registration method which is
      implemented by combining edge preserving scale space with the free form
      deformation. The edge preserving scale space which is able to select edges and
      contours of an image according to their geometric size is derived from the total
      variation model with the L1 norm (TV-L1). At each scale, the selected edges and
      contours are sufficiently strong to drive the deformation using the FFD grid,
      then the deformation fields are gained by a coarse to fine manner.Datasets were
      collected from 5 patients treated under the PET-CT scanner (GE medical systems,
      Discovery LS). Before treatment planning, the GTV (gross tumor volume) is
      delineated on every section of the PET scans by the radiation oncologist and the
      Result will be compared with proposed automatic segmentation method. Of the 5
      patients investigated here, all are non-small cell lung carcinoma (NSCLC)
      patients. RESULTS: After evaluation of the experiment results by three clinical
      oncologists, they concluded that the segmentation results are very close to the
      manual results and the GTV contours on CT scan which is produced by the
      deformation field automatically can be used for radiation therapy planning. The
      volumetric overlap is on an average 90%-97% comparing with manually segmented
      tumors by oncologists. CONCLUSIONS: We can conclude that an efficient tumor
      positioning method is proposed by jointly registration and segmentation for FDG
      PET-CT datasets.

PMID- 28517634
TI  - SU-E-I-98: PET/CT's Most-Cited 50 Articles since 2000: A Bibliometric Analysis of
      Classics.
AB  - PURPOSE: Despite its relatively recent introduction to clinical practice, PET/CT
      has gained wide acceptance both in diagnostic and therapeutic applications.
      Scientific publication in PET/CT has also experienced significant development
      since its introduction. Bibliometric analyses allow an understanding of how this
      publication trend has developed at an aggregated level. Citation analysis is one
      of the most widely used bibliometric tools of scientometrics. Analysis of
      classics, defined as an articles with 100 or more citations, is common in the
      biomedical sciences as it reflects an article's influence in its professional and
      scientific community. Our objective was to identify the 50 most frequently cited
      classic articles in PET/CT in the past 10 years. METHODS: The 50 most-cited
      PET/CT articles were identified by searching ISI's Web of Knowledge and Pubmed
      databases for all related publications from 2000 through 2010. Articles were
      evaluated for several characteristics such as author(s), institution, country of
      origin, publication year, type, and number of citations. An unadjusted
      categorical analysis was performed to compare all articles published in the
      search period. RESULTS: The search yielded a cumulative total of 22,554 entries
      for the publication period, of which 15,943 were original research articles. The
      50 most-cited articles were identified from the latter sum and selected out of 73
      classics. The number of citations for the top 50 classics ranged from 114 to 700.
      PET/CT classics appeared in three general and 12 core journals. The majority of
      the classics were in oncologic applications of PET/CT (62%). Articles related to
      diagnostic topics were 6%. The rest were focused on physics and instrumentation
      24% and other basic sciences 16%. CONCLUSIONS: Despite its relatively short
      history PET/CT accumulated 73 classic articles in a decade. Such information is
      of importance to researchers and those who wish to study the scientific
      development in the field.

PMID- 28517635
TI  - SU-E-I-65: Magnetic Resonance Spectroscopy of the Prostate: A Phantom Study of
      Metabolite Concentrations.
AB  - PURPOSE: Magnetic Resonance Spectroscopy (MRS) of the prostate is not used in
      radiotherapy departments on a regular basis due to a number of issues. The
      indication and severity of prostate cancer is related to the presence of choline
      in the prostate, in particular, the ratio of choline (plus creatine) to citrate.
      In-vivo data supports this theory only marginally but lacks strong correlation
      with biopsy data. The situation is further complicated by the lack of precise
      spatial information in biopsy, variation of magnetic susceptibility, and spatial
      dependence of MRS data on the distance from the endo-rectal coil. The latter also
      cause low signal-to-noise ratio (SNR). We intend to understand how the level of
      metabolite concentrations and spatial dependences determine what is observed in
      MRS. METHODS: A spherical phantom is filled with water solutions containing
      various amounts of metabolites. It is placed on top of an endo-rectal coil with
      the balloon filled with per fluorocarbon. MRS data is acquired on a GE 1.5 T MR
      scanner. The metabolite values, their ratios etc as reported in GE software,
      FuncTool are studied as functions of metabolite concentrations in the phantom.
      RESULTS: Analysis of the phantom data indicates that the metabolite ratio
      reported in FuncTool is approximately linearly correlated to the metabolite
      concentrations used in the phantom to a certain point and then saturates whereas
      the largest metabolite value is well correlated with its concentration in the
      phantom. All metabolite values become weaker and SNR lower as we move away from
      the coil. CONCLUSIONS: This work indicates the potential of using metabolite
      values directly provided their spatial dependences on the distance of the voxels
      from the endo-rectal coil can be accommodated.

PMID- 28517636
TI  - SU-E-I-109: Sensitivity Analysis of an Electronic Portal Imaging Device Monte
      Carlo Model to Variations in Optical Transport Parameters.
AB  - PURPOSE: To investigate the sensitivity of a Monte Carlo (MC) model of a standard
      clinical amorphous silicon (a-Si) electron portal imaging device (EPID) to
      variations in optical photon transport parameters. METHODS: The Geant4 MC toolkit
      was used to develop a comprehensive model of an indirect-detection a-Si EPID
      incorporating x-ray and optical photon transport. The EPID was modeled as a
      series of uniform layers with properties specified by the manufacturer
      (PerkinElmer, Santa Clara, CA) of a research EPID at our centre. Optical
      processes that were modeled include bulk absorption, Rayleigh scattering, and
      boundary processes (reflection and refraction). Model performance was evaluated
      by scoring optical photons absorbed by the a-Si photodiode as a function of
      radial distance from a point source of x-rays on an event-by-event basis (0.025
      mm resolution). Primary x-ray energies were sampled from a clinical 6 MV photon
      spectrum. Simulations were performed by varying optical transport parameters and
      the resulting point spread functions (PSFs) were compared. The optical parameters
      investigated include: x-ray transport cutoff thresholds; absorption path length;
      optical energy spectrum; refractive indices; and the 'roughness' of boundaries
      within phosphor screen layers. RESULTS: The transport cutoffs and refractive
      indices studied were found to minimally affect resulting PSFs. A monoenergetic
      optical spectrum slightly broadened the PSF in comparison with the use of a
      polyenergetic spectrum. The absorption path length only significantly altered the
      PSF when decreased drastically. Variations in the treatment of boundaries
      noticeably broadened resulting PSFs. CONCLUSIONS: Variation in optical transport
      parameters was found to affect resulting PSF calculations. Current work is
      focusing on repeating this analysis with a coarser resolution more typical of a
      commercial a-Si EPID to observe if these effects continue to alter the EPID PSF.
      Experimental measurement of the EPID line spread function to validate these
      results is also underway. Cancer Institute NSW Research Equipment Grants 10/REG/1
      20 and 10/REG/1-10 Cancer Council NSW Grant, ID RG 11-06 NHMRC Project Grant,
      ID569211 The University of Sydney Postgraduate Research Scholarship in Medical
      Physics SWSCS Radiation Oncology Student Scholarship, 2012.

PMID- 28517637
TI  - SU-E-I-75: A New Method for Prostate Cancer Localization Using Multispectral MRI.
AB  - PURPOSE: To develop a new method for automatic localization of prostate cancer
      using multispectral MRI data. METHODS: Multispectral MRI including MR
      spectroscopic imaging (MRSI), T2 weighted MRI, diffusion weighted imaging (DWI)
      and dynamic contrast-enhanced (DCE) MRI, has been used for cancer target
      localization. The combination of multiple MRI imaging technologies provides more
      useful information than one single technology alone about prostate cancer and has
      advantages for target definition in radotherapy treatment and quantitative
      evaluation of tumor response. However, manual cancer localization using
      multispectral MRI dataset is a tedious task and prone to inter-/intra-observer
      variability. Automatic localization methods using multispectral MRI data is
      highly desired. In this paper, a fuzzy fusion framework for automatically
      localizing prostate cancer with multispectral MRI data is presented. Firstly, for
      each kind of MRI images, a membership function is created to calculate the
      membership-degrees of image elements belonging to cancer region. Secondly, a
      fuzzy fusion operator is used to fuse different membership- degrees corresponding
      to the same regions. Lastly, the Result of fusion is further adjusted with fuzzy
      region growing process, leading to the final membership-degree map. And cancer
      volume is finally defined by setting up a threshold on the map. RESULTS: The new
      method was tested with one multispectral MRI patient dataset and results from our
      experimental study are compared with the one obtained form a manual method
      performed by an experienced pathologist. Quantitative analysis shows that the
      specificity is 98.89%, sensitivity is 62.85% and accuracy is 95.42%,
      respectively. It illustrates the feasibility of utilizing this framework in the
      clinical application. CONCLUSIONS: The feasibility study shows the new method
      reported in this paper achieves automatic localization for prostate cancer and
      can be easily implemented in clinical applications. We are currently conducting a
      clinical study for testing the effectiveness and reliability, and further
      developing this method. *supported by NSFC-81171342 support by National Science
      Foundation of China (NSFC-81171342).

PMID- 28517638
TI  - SU-E-I-91: Development of a Compact Radiographic Simulator Using Microsoft
      Kinect.
AB  - PURPOSE: Radiographic simulator system is useful for learning radiographic
      techniques and confirmation of positioning before x-ray irradiation. Conventional
      x-ray simulators have drawbacks in cost and size, and are only applicable to
      situations in which position of the object does not change. Therefore, we have
      developed a new radiographic simulator system using an infrared-ray based three
      dimensional shape measurement device (Microsoft Kinect). METHODS: We made a
      computer program using OpenCV and OpenNI for processing of depth image data
      obtained from Kinect, and calculated the exact distance from Kinect to the object
      by calibration. Theobject was measured from various directions, and positional
      relationship between the x-ray tube and the object was obtained. X-ray projection
      images were calculated by projecting x-rays onto the mathematical three
      dimensional CT data of a head phantom with almost the same size. The object was
      rotated from 0 degree (standard position) through 90 degrees in increments of 10
      degrees, and the accuracy of the measured rotation angle values was evaluated. In
      order to improve the computational time, the projection image size was changed
      (512*512, 256*256, and 128*128). RESULTS: The x-ray simulation images
      corresponding to the radiographic images produced by using the x-ray tube were
      obtained. The three-dimensional position of the object was measured with good
      precision from 0 to 50 degrees, but above 50 degrees, measured position error
      increased with the increase of the rotation angle. The computational time and
      image size were 30, 12, and 7 seconds for 512*512, 256*256, and 128*128,
      respectively. CONCLUSIONS: We could measure the three-dimensional position of the
      object using properly calibrated Kinect sensor, and obtained projection images at
      relatively high-speed using the three-dimensional CTdata. It was suggested that
      this system can be used for obtaining simulated projection x-ray images before x
      ray exposure by attaching this device onto an x-ray tube.

PMID- 28517639
TI  - SU-E-I-102: Independent Implementation of AAPM TG-150 Draft Image Receptor Test
      Recommendations.
AB  - PURPOSE: To determine whether a proposed suite of generic tests for digital
      radiography (DR) detectors could be reduced to practice. METHODS: MATLAB software
      was developed to analyze images according to descriptions in a document drafted
      by the TG150 Detector Subgroup. Forprocessing images were acquired directly from
      the acquisition stations of three DR and one Computed Radiography system. Images
      included flat-field exposures at the manufacturer's calibration condition, twice
      the exposure, 1/2 the exposure, and a low exposure, plus three images of a lead
      bar pattern in different orientations, also at the calibration condition. The
      flat field images were analyzed to determine Detector Response; Gain Correction;
      Signal, Noise, and Signal-to-noise (SNR) Uniformity; SNR Magnitude; and Anomalous
      Detector Element (del) Identification. The program also allowed visual inspection
      for evaluation of collimation and non-uniformity. Bar pattern images were
      analyzed to evaluate spatial resolution by a variance method. RESULTS:
      Acquisition revealed a number of pitfalls. Some manufacturers have multiple
      calibration points. For-processing images are not directly available from all
      systems, and PACS may modify them from their original state. The orientation of
      the flat field with respect to the anodecathode axis may not be defined by the
      manufacturer. Care must be taken to ensure collimation outside the edges of
      detectors, or the software must exclude collimator shadows. The matrix size of
      images differs among manufacturers, so the size of the region of interest (ROI)
      for analysis varies from the default size of 100*100 dels, as does the number of
      ROIs. The approach for dealing with edges and ROIs may affect the numerical
      results. The detector response function may also affect the interpretation of
      results. CONCLUSIONS: The software successfully implements most of the detector
      tests recommended by TG150. Comparison of these results with those of the
      parallel effort will validate the draft test definition.

PMID- 28517640
TI  - SU-E-I-69: Magnetic Resonance Metal Artifact Evaluation with Routine Clinical
      Cardiac Sequences.
AB  - PURPOSE: To examine schemes to grade the severity of metal susceptibility
      artifacts on image quality using cardiac MRI pulse sequences. METHODS: A post
      thoracotomy patient was simulated with a stainless steel sternal wire
      (Syneture,MA; size=6, diameter=48mm), placed securely on an ACR MRI phantom.
      Phantom was scanned on a 1.5-T Siemens using cardiac MRI sequences:1)TrueFISP,
      2)Gradient-Recalled-Echo (GRE), 3)Turbo-Spin- Echo (TSE), 4)Turbo-Inversion
      Recovery-Magnitude (TIRM), 5)Dark- blood-IR-FS (DBFS) with and without the wire
      (FOV=30*30cm, slice- thickness/slice-gap=7.0/1.5mm, matrix size=192*192,
      slices=17). Image quality degradation was assessed in terms of signal loss and
      spatial deformation; signal loss by a) measuring the largest diameter of signal
      drop and b) number of slices with a signal drop and spatial deformation in
      VelocityAI (Atlanta,GA) by computing the rigid transformation indices between the
      phantom's internal grid with and without the metal. RESULTS: Image quality was
      evaluated in terms of signal loss, spatial deformation and ring artifacts. Signal
      loss: TruFISP and GRE showed the largest signal drop diameter (13 and 16cm
      respectively). GRE sequence showed a signal drop in -12 slices where as signal
      drop occurred in only ~4-5 slices with other sequences. Spatial deformation: GRE
      sequence showed the maximum with a ~9mm grid deflection followed by TSE and DBFS
      (~8mm). An average deflection of 5.4mm was observed on most of the sequences
      except T rueFISP and TIRM (Omm). Rigid body transformation showed a maximum x,y,z
      translation of -4.7, 0.3 and 1.69 mm and x,y,z-angular rotation of 0.2, - 1.5 and
      0.5 degrees  for GRE sequence followed by TSE and DBFS confirming the spatial
      distortion results. Concentric ring artifacts with signal loss were also observed
      on TrueFISP and DBFS images. CONCLUSIONS: Quantification of cardiac MR sequences
      to metal tolerance and the impact on image quality has shown that GRE and
      TrueFISP are the most metal-susceptible and TIRM is the most metal-tolerant
      sequence in terms of both signal loss and spatial deformation. This study helped
      in creating a separate cardiac metal protocol comprising of mainly metal-tolerant
      sequences thus reducing scan time and patient discomfort.

PMID- 28517641
TI  - SU-E-I-79: Correction of Dark Current and Image Lag in Multi-Source Carbon
      Nanotube Imaging Systems.
AB  - PURPOSE: To correct for dark current and detector image lag in multi-source
      carbon nanotube (CNT) based imaging systems. METHODS: CNTs can be used as a novel
      electron source for X-ray generation. Here a small (~2 kV) gate voltage induces a
      large electric field at the CNT tip that causes field emission as opposed to
      thermionic emission. This enables faster switching times and allows
      miniaturization which aids in the development of stationary multi-source systems.
      These systems may encounter two key problems: dark current in non-active sources
      and detector lag. In damaged and perhaps end-of-life devices, sources may develop
      significant electron output without gate voltage, interfering with images from
      non-active sources. Although the output is small, it is constant, and continuous
      integration of detectors compared with small X-ray exposure time magnifies its
      contribution to the signal. A method based on binary multiplexing is developed to
      mitigate the dark current contributions possibly extending device lifetime.
      Having discrete sources, these multi-source systems have coarser angular sampling
      than rotating systems. This coarser sampling means that the detector signal
      changes more in adjacent projections than rotating systems exacerbating the
      effect of detector lag. Since flat panel detectors have a capacitive behavior,
      readout only removes some charge from pixels. As a result, a device dependent
      amount (6.6% in our device) of the signal from the current image contributes to
      the subsequent image. A fast, stable inverse filter separating detector lag has
      been developed. RESULTS: Projection data were simulated based on parameters
      measured from a multi-source CNT system. Incorporating dark current and image lag
      phenomena into reconstruction improves contrast to noise ratio. CONCLUSIONS:
      These correction methods can be easily implemented on clinical multi-source
      systems to improve image quality and extend the device's usable lifetime.
      Supported in part by Siemens Medical.

PMID- 28517642
TI  - SU-E-I-62: Investigation of Dominant Factors Affecting Fatigue in Image Reading
      of Radiologists.
AB  - PURPOSE: To investigate dominant factors affecting fatigue in image reading of
      radiologists. METHODS: Two kinds of fatigue were assessed in this study. One was
      fatigue in the central nervous system evaluated by the critical fusion frequency
      (CFF). The other was eye fatigue evaluated by a score determined from a
      questionnaire based on the oculomotor strain subscale from the Simulator Sickness
      Questionnaire (SSQ). When fatigue increases, the CFF and the SSQ score indicate
      low and high values, respectively. The fatigue of seventeen radiologists was
      assessed before and after their daily image reading. The reading times and the
      numbers of images were different among the assessments, and ranged about 1.5 -
      5.0 hours and 1,000 - 12,000 images, respectively. The assessments of fatigue
      were repeated four times for each radiologist on different days. Finally, the
      measurements of the two kinds of fatigue were analyzed in terms of years of
      experience, age, sleeping time the previous night, ambient light conditions,
      reading time, and the numbers of interpreted images, series, and cases. RESULTS:
      The CFF and SSQ score after image reading were significantly lower and higher
      than those measured before image reading, respectively. Younger and less
      experienced radiologists indicated a higher level of fatigue than older and more
      experienced radiologists in both the CFF and the SSQ score. When radiologists
      interpreted clinical images for longer hours, the SSQ score tended to be higher.
      On the other hand, there was little incremental difference in the CFF among
      different lengths of reading time. No obvious differences were observed in the
      other items. CONCLUSIONS: Less experience with reading images, a younger age, and
      a longer reading time could be dominant factors affecting fatigue in image
      reading.

PMID- 28517643
TI  - SU-E-I-72: Modulation of Hypothalamic Connectivity by Food Ingestion.
AB  - PURPOSE: In this study we utilized resting state fMRI (rsfMRI) to identify and
      compare hypothalamic connectivity in lean subjects during fasting and satiated
      state. METHODS: rsfMRI were performed on 7 healthy lean subjects (4 male, 3
      female, 20-35 yo, BMI = 18-25 kg/m2 ). Subjects fasted overnight (8 hrs), average
      blood glucose of 80+/- 5 mg/dL. None of the subjects were on diet program or
      recently lost/gain weight. rsfMRI EPI parameters:TR = 3000ms, TE = 30 ms, and
      spatial resolution of 1.7 * 1.7 mm * 5mm, ST= 65 mins (10-min pre-glucose
      ingestion acquisition, followed by 50 mins of post-glucose ingestion). During
      rsfMRI, subjects ingested standard glucola (75 g of glucose dissolved in 296 ml
      of flavored water) over 4.5 +/- 0.75 min via a peroral rubber tube. Preprocessing
      procedure was implemented using FSL consisting of 1) motion correction 2) spatial
      smoothing, 3) temporal filtering between 0.01-0.08 Hz. Using the Talairach-Daemon
      atlas, ROI in the hypothalamus was selected. The individual timeseries of
      hypothalamus was used as seed to find neural structures that share similar
      temporal pattern that hypothalamus. RESULTS: Structures that were engaged only
      during fasting were (Table 1): Inferior frontal gyrus (BA 47) has been linked to
      the modulation of hunger. The output from the orbitofrontal cortex to both
      striatum (lentiform nucleus) and lateral hypothalamus has been reported. The
      structures that were engaged only during satiated state were: Superior temporal
      gyrus has been implicated in food inhibition and mid temporal gyrus has been
      reported to be engaged in satiation. Cerebellum is activated when the brain is
      monitoring its sensory systems.

PMID- 28517645
TI  - SU-E-I-104: Detector Lag Testing for Digital Radiography.
AB  - PURPOSE: Signal lag is an inherent property of the digital detectors used for
      radiography. The extent and impact of signal lag can vary. In this exhibit we aim
      to:'c provide context for detector lag testing as a matter of acceptance testing
      for detectors used in digital radiography (DR)'c provide example lag data from
      various DR systems. Lag measurement and analysis techniques have been published
      but without the expected results that are useful for benchmarking.'cbring greater
      awareness and understanding to the impact of detector lag for the performance of
      digital detectors and the appearance of image ghosting in clinical images.
      METHODS: A standardized method was used for the quantification of lag similar to
      that described in the IPEM report 32 part vii [1]. Six different vended detector
      options were measured and compared. RESULTS: Lag images were visually compared
      and lag measurement values were normalized using the measured signal transfer
      properties of each system. The results are shown as normalized with exposure. The
      results show a wide variety of lag responses, even for the same physical detector
      hardware but different vendor implementations. CONCLUSIONS: The ultimate test for
      detector lag performance is whether residual 'ghost' images appear in clinical
      images. Some vendor systems are more prone to the appearance of lag than others.
      We attempt to quantify system properties at acceptance testing that can enable
      discriminationbetween systems which have poor or superior lag properties. A
      suggested easurement analysis technique which normalizes data to be linear with
      exposure does not appear to adequately assess the likelihood for the clinical
      appearance of lag. [1] Mackenzie A et al. Measurement of the Performance
      Characteristics of Diagnostic X-Ray Systems: Digital Imaging Systems. Institute
      of Physics in Medicine 2009 (IPEM Report 32, part vii). 2010.

PMID- 28517646
TI  - SU-E-I-115: Wavelet Analysis of Ultrasound Image for the Diagnosis of Sjogren's
      Syndrome.
AB  - PURPOSE: Sjogren's syndrome (SS) is an auto-immune disease presenting with dry
      eyes and mouth (keratoconjunctivitis sicca and xerostomia). Ultrasonography is
      used for the initial and non-invasive investigation of the parotid gland in the
      disease. The purpose of this study is to develop an image processing for
      diagnosis of SS by applying wavelet analysis to ultrasound image. METHODS:
      Ultrasound B-mode images of the parotid gland were captured and analyzed by a
      personal computer. A square region of interest (ROI) was set on the image and two
      dimensional discrete wavelet transform was performed within the ROI. As a Result,
      the image was decomposed into an approximate image and three detailed images in
      vertical, horizontal and diagonal directions in different scales. A feature
      quantity for image classification was defined by calculating from the wavelet
      coefficients of detailed images within selected scales. The ultrasound images of
      80 patients who had been referred to Nagasaki University Hospital because of
      suspicion of SS were analyzed. A total of 37 patients fulfilled the criteria for
      SS, whereas the remaining 43 patients did not. The severity of SS was graded into
      four degrees by sialography. The images with each feature quantity were
      classified by statistical cluster analysis. RESULTS: In this method, the images
      can be divided into two groups which mainly contained SS and non-SS. The
      sensitivity and specificity in the detection of SS was 78% and 95%, respectively.
      It was also found that the defined feature quantity tended to change with the
      severity of SS. CONCLUSIONS: In ultrasonography, the image analysis based on
      wavelet transform was useful for the diagnosis of Sjogren's syndrome.

PMID- 28517647
TI  - SU-E-I-86: Image Fusion Verification Using a Vendor-Independent Phantom.
AB  - PURPOSE: To evaluate the image fusion accuracy of a hybrid PET/CT or SPECT/CT
      system using a recently developed vendor-independent phantom. METHODS: The basic
      design of the fusion verification phantom is a 10 cm urethane cube with three 1
      mm diameter channels each fitted with standard Luer connection designed to be
      filled with a radioactive solution. The channels also have a 0.4 mm diameter
      steel wire inserted in each channel. There are two versions of this cube phantom
      with different orientations of the wire/liquid filled channels. There is the
      perpendicular cube with three channels each parallel to the x, y and z axes. The
      second cube orientation has two opposing angled channels and one that is
      perpendicular to the cube base. When imaged with either a PET/CT or SPECT/CT
      device the wire yields a high contrast image against a high signal target of the
      radioisotope filled channel. Both phantoms are scanned on various vendor and
      model hybrid systems. RESULTS: Three plane reconstructed data of the
      perpendicular fusion phantom generates images with point source like targets of
      the emission and transmission data for quick visual evaluation of registration
      accuracy for x, y and z shifts. A series of axial reconstructed images can be
      used to evaluate alignment when using the opposing ramp fusion phantom. The
      unique utility of the opposing ramps allows for verification of a z-axis offset
      from the single axial image data. Alignment data are presented from a number of
      PET/CT and SPECT/CT systems. CONCLUSIONS: The use of either the perpendicular or
      opposing ramp fusion phantom provides a convenient QC vendor independent tool for
      evaluation of image alignment accuracy of hybrid imaging systems. The design
      supports a simple 3D processing with a straightforward visual interpretation of
      alignment.

PMID- 28517649
TI  - SU-E-I-64: 1H-MRS Quality Assurance in Short and Long Term Using a Phantom
      Object.
AB  - PURPOSE: To evaluate intrinsic variability of 1H-MRS single voxel technique for
      short and long periods of time using a metabolic phantom in a clinical protocol
      (hippocampi). METHODS: A solution with several metabolites (NAA, Cre, Cho, Lac, M
      Ins, Glu, Gln) was placed in a spherical round glass with 300 mL. MRS data were
      acquired in a 3 T MRI scanner, with a PRESS sequence of TE/TR=35/1500 ms, 2048
      data points, 1725 Hz of bandwidth, 6 cm3 VOI centered in the phantom and NSA of
      128. A total of 130 spectra were obtained from 27 acquisition dates (5
      spectra/date without removing the phantom) over 15 months. Spectra were processed
      with LCModel software to reduce the human variability during spectra processing.
      SNR and FWHM outputs from LCModel are mean calculated values from identified
      resonances. RESULTS: Spectra from each acquisition date showed no mean deviations
      superior to 4% for all metabolites except for Lac (14 %). During 15 months all
      metabolites showed inferior deviations to 12%, once again except for Lac (20.5%).
      The worst estimated concentration was from Gln, which represent 60% of the
      expected value. The mean SNR was 16.3+/-2.1. There was no correlation between SNR
      and mean FWHM from resonances, thus wrong water suppression must be the main
      factor for variable SNR. CONCLUSIONS: NAA was the most stable metabolite in the
      whole analysis period with a variation of 6.8%, and Gln was the less stable with
      a 25.4% variation. FWHM was more variable than SNR, possible due to shimming
      variability, although it showed no influence in SNR. It was observed two types of
      artifacts in some spectra generated by unbalanced gradients, B0 inhomogeneity and
      also insufficient amplitude from crusher gradients. Temporal analysis
      demonstrated the feasibility of compare results obtained on measurements of the
      same date and for long periods due to low deviations provided by the technique.

PMID- 28517650
TI  - SU-E-I-108: Simple Approach to Determine Patient's Entrance Skin Exposure for
      Radiographic.
AB  - PURPOSE: To evaluate a model which can predict patient's Entrance Skin Exposure
      (ESE) from height and weight and a single kVp mR/mAs measurement for
      radiographic. METHODS: Patient height, weight and post exposure mAs are obtained
      to assess ESE based on IAEA model. Patient's thickness is obtained by assuming a
      cylindrical geometry. The validity of this assumption is tested against actual
      measurements. Source to Skin Distance (SSD) is computed from patient's thickness
      and the Source-Image receptor Distance (SID) used during exposure. Entrance Skin
      Exposure is calculated as a product of post exposure mAs and a single 80 kVp
      mR/mAs obtained at a reference distance corrected inversely for SSD. Values of
      mR/mAs at other kVp's are obtained by quadratic variation of output with kVp.
      RESULTS: The validity of predicting patient thickness will be presented based on
      numerous measurements performed on test subjects. Deviation between the ESE
      values using of single kVp, mR/mAs measurement and the ones obtained by the
      conventional multiple kVp mR/mAs will be presented as well. CONCLUSIONS: This
      work indicates a simple approach to determine the patient's ESE based on the
      patient's height and weight for radiographic units, which will be very useful for
      institutions that do not have a dedicated physicist.

PMID- 28517648
TI  - SU-E-I-97: Characterizing the Modulation Transfer Function (MTF) of Proton
      Radiography.
AB  - PURPOSE: To characterize the modulation transfer function (MTF) of proton
      radiography using GEANT4 Monte Carlo simulations. METHODS: A phantom was
      specifically modeled using five main materials: bone (1.92 g/cm3 ), muscle (1.2
      g/cm3 ), water (1.0 g/cm3 ), adipose tissue (0.9 g/cm3 ), and lung (0.3 g/cm3 ).
      The basic geometry of the phantom consists of cube-shaped inserts of biological
      materials placed in water. The thickness of the water, the size of the cube, the
      depth of the cube in the water, and the proton beam energy have all been varied
      and studied. The contrast-to-noise ratio (CNR) between the two materials was
      evaluated at multiple points along a line-of-interest (LOI) in order to
      ultimately characterize the spatial resolution by the 10% point of the modulation
      transfer-function (MTF10% or MTF 10). RESULTS: The MTF was generated for
      interfaces of water-lung, water-bone, water-muscle, water-adipose. This study
      indicates that proton radiography can distinguish one material from another with
      a resolution better than 1 mm for water-adipose and water-muscle or sub
      millimeter in cases of water-bone and water-lung interfaces. CONCLUSIONS: The sub
      millimeter resolution of proton radiography offers clinicians a potentially tool
      in specific tumor diagnostics (such as in lung cancer), patient-setup for daily
      proton therapy, and the reduction of absorbed dose delivered when compared to
      photon imaging.

PMID- 28517651
TI  - SU-E-I-74: White Matter Tract Disintegrate of Frontal and Limbic Regions in Mild
      Cognitive Impairment with Depression.
AB  - PURPOSE: Mild cognitive impairment with depression (MCID) is common and
      associated with disability and cognitive impairment, with high probability of
      relapse. Hypothesize that 1) a sign of WM disintegration would be observed in
      MCID than MCI nondepression (MCIND), especially in frontal and limbic regions and
      patients with depression would show reduced GM density in the hippocampus,
      amygdala, anterior gyrus cingulate, and dorsolateral prefrontal cortex (DLPFC)
      and dorsomedial prefrontal cortex (DMPFC) 2) the abnormalities of long
      association fiber tracts integrity are correlated with geriatric depression.
      METHODS: Forty-two subjects (20 nondepressed, 22 depressed) underwent DTI and
      cognitive assessment. Depression was initially assessed by means of the Korean
      version of the 30-item Geriatric Depression Scale (K-GDS). All patients scoring
      19 or higher on the K-GDS were screened as depressed. An automated tract-based
      statistical analysis method was used to derive estimates of fractional anisotropy
      (FA) for each subject. Group effects and correlations with clinical features on
      DTI parameters were examined. RESULTS: We found cross-sectional differences in WM
      tract disintegration on posterior cingulum, splenium of corpus callosum, uncinate
      fasciculus, genu, thalamus, internal and external capsule of limbic in MCID.
      These results support changes in the structural integrity of neuronal cells in
      these specific important brain regions constituting a fronto-limbic-cerebellar
      network during depressive and in particular during the course of depression. The
      different parts of the frontal lobes have afferent and efferent connections with
      other neocortical, limbic, and subcortical regions and participate in the limbic
      cortico-striatal-pallidal-thalamic circuits. CONCLUSIONS: Findings are suggestive
      of loss of integrity in WM fiber within frontal, temporal and limbic regions,
      increasing the evidence that implicates disruptions to the limbic-orbitofrontal
      networks in the pathogenesis of MCID. These neuroanatomical circuits play an
      important role in the regulation and modulation of affect and emotion, and
      contribute to the pathogenesis of late-life depression.

PMID- 28517652
TI  - SU-E-I-90: Fast and Robust Algorithm Towards Vessel Lumen and Stent Strut
      Detection in Optical Coherence Tomography.
AB  - PURPOSE: Optical Coherence Tomography (OCT) is a catheter-based imaging method
      that employs near-infrared light to produce high-resolution cross-sectional
      intravascular images. We propose a new segmentation technique for automatic lumen
      area extraction and stent strut detection in intravascular OCT images for the
      purpose of quantitative analysis of neointimal hyperplasia (NIH). METHODS: Two
      clinical dataset of frequency-domainOCT scans of the human femoral artery were
      analyzed. First, a segmentation method based on Fuzzy C-Means (FCM) clustering
      and Wavelet Transform (WT) was applied towards inner luminal contour extraction.
      Subsequently, stent strut positions were detected by utilizing metrics derived
      from the local maxima of the wavelet transform into the FCM membership function.
      RESULTS: The inner lumen contour and the position of stent strut were extracted
      with very high accuracy. Compared with manual segmentation by an expert
      physician, the automatic segmentation had an average overlap value of 0.917 +/-
      0.065 for all OCT images included in the study. The strut detection procedure
      successfully identified 6.7 +/- 0.5 struts for each OCT image. CONCLUSIONS: A new
      fast and robust automatic segmentation technique combining FCM and WT for lumen
      border extraction and strut detection in intravascular OCT images was designed
      and implemented. The proposed algorithm may be employed for automated
      quantitative morphological analysis of in-stent neointimal hyperplasia.

PMID- 28517653
TI  - SU-E-I-101: Initial Implementation and Evaluation of AAPM TG-150 Draft Image
      Receptor Non-Uniformity Testing Recommendations.
AB  - PURPOSE: To implement in software the procedures described in AAPM Task Group
      150's draft recommendations for image receptor performance testing, and to
      evaluate the effectiveness and practicality of these procedures. METHODS: Images
      of flat fields were acquired using digital x-ray image receptors at 6 cooperating
      institutions. Four flat field images obtained with each detector spanned a range
      of input detector air kerma. Software based on AAPM TG150's draft report
      processed the test images and generated results. Image receptor response and
      several measures of non-uniformity were evaluated. Images were divided into 10 mm
      square regions, after eliminating 10 mm borders. For each region, signal (mean),
      noise (standard deviation) and SNR were calculated. Characteristic signal, noise
      and SNR were calculated based on average values from all regions. Local non
      uniformity for signal (SLN), noise (NLN) and SNR (SNRLN) were expressed as the
      maximum ratio of the absolute difference between each region's value and its 4
      nearest neighbors, to the respective characteristic value. Global non-uniformity
      (SGN, NGN, SNRGN) were expressed similarly but differences between maximum and
      minimum values obtained from the regions were used (without comparison to local
      neighbors). RESULTS: TG150 tests discriminated between good and poorly performing
      detectors. Improper detector calibration was detectable, with noise non
      uniformity proving to be a more sensitive measure than signal or SNR non
      uniformity. Detector rotation relative to calibration conditions produced a
      greater change in signal non-uniformity than the other measures. Image receptor
      structured noise was characterized by an increase in noise non-uniformity with
      incident air kerma. CONCLUSIONS: AAPM TG150's proposed approach to image receptor
      testing was implemented and evaluated. The approach appears to be an effective
      and practical one for routine quality assurance testing of digital radiographic
      image receptors.

PMID- 28517654
TI  - SU-E-I-68: The Effect of Partially Parallel Imaging on SNR Across Scanning
      Platforms.
AB  - PURPOSE: Different manufacturers implement partially parallel imaging (PPI) with
      different proprietary reconstruction methods and algorithms. Additionally, signal
      to noise ratio (SNR) associated with PPI is highly dependent on coil design and
      conformation, as quantified by the g-factor. This potentially leads to
      differences in SNR across coils and scanners. This study seeks to characterize
      the impact of PPI on SNR across four MRI platforms. METHODS: Turbo spin echo
      (TSE) scans of a spherical phantom filled with an aqueous solution were acquired
      in a head coil on a 3T Siemens Tim Trio, 3T Philips Achieva, 1.5T Toshiba Vantage
      and 3T GE Signa Excite HD. Scans at each available integer R-value and
      reconstruction method were taken on each scanner. SNR was measured in each image
      using the difference method. SNR was normalized to a maximum value of 1.0 for
      each reconstruction method. Linear regressions and percent change in SNR relative
      to R-value were determined for each reconstruction method. Coefficient of
      variation (CV) was used to determine the relationship between PPI
      implementations. RESULTS: Slopes of the linear regressions ranged from *0.24 to
      *0.27. Percent SNR on average was 67.3%+/-3.7%, 43.3%+/-2.9% and 27.4%+/-6.9% of
      the associated non-PPI scan at R=2, 3 and 4 respectively. The range of percent
      SNR relative to non-PPI scans was 62.1%-71.7%, 39.8%-46.8% and 20.7%-34.5% at
      R=2, 3 and 4 respectively. The CV was 7.75% at R=2, 16.05% at R=3 and 21.79% at
      R=4. CONCLUSIONS: Slopes of the linear regressions ranged from -0.24 to -0.27.
      Percent SNR on average was 67.3%+/-3.7%, 43.3%+/-2.9% and 27.4%+/-6.9% of the
      associated non-PPI scan at R=2, 3 and 4 respectively. The range of percent SNR
      relative to non-PPI scans was 62.1%-71.7%, 39.8%-46.8% and 20.7%-34.5% at R=2, 3
      and 4 respectively. The CV was 7.75% at R=2, 16.05% at R=3 and 21.79% at R=4.

PMID- 28517655
TI  - SU-E-I-112: Pre-Clinical Imaging with an Ultra-High Resolution X-Ray Detector.
AB  - PURPOSE: To explore the possible applications for a newly developed ultra-high
      resolution, small field-of-view (FOV) micro-solid state x-ray image intensifier
      (micro-SSXII) detector. METHODS: The micro-SSXII is based on an 8 micron, 1004 by
      1002 electron-multiplying CCD (EMCCD) optically coupled to a 100-micron thick
      CsI(Tl) phosphor through a fiber optic window resulting in a FOV of 8 mm with a
      resolution limit of more than 20 lp/mm. The system has the capability of
      providing real-time images at low exposures because of the high variable gain of
      the EMCCD. Several phantoms were prepared by filling catheter tubes of 470 micron
      internal diameter with separate mixtures of a casting resin with different ratios
      of three different contrast agents (Omnipaque 350, barium sulphate, tantalum
      powder). These were imaged with the micro-SSXII at 50 kVp to help select the best
      mixture for use in making a cast of a rat kidney whose vasculature would then be
      made radiopaque and visualized. RESULTS: The images of all phantoms showed
      clumping of these contrast agents within the resin resulting in a non-uniform
      mix. The image of the phantom filled with Omnipaque and resin in a 1:4 ratio
      showed the best mixture although large bubble formation of the iodine was
      observed. This combination was used to make a cast of a rat kidney vasculature
      and imaged with the micro-SSXII. Small iodine bubbles with diameters as small as
      25 microns were clearly delineated in the rat kidney vessels confirming the sharp
      detail capability of the micro-SSXII. CONCLUSIONS: The micro-SSXII in combination
      with a soft x-ray spectrum can provide excellent images of small animal casts
      prepared with an appropriate radiopaque resin to study finer details of the
      vasculature. This new imager has the potential to be used for region-of-interest
      x-ray image guidance for interventional studies in small animals. Supported in
      part by: NIH Grants R01-EB008425, R01-EB002873 and an equipment grant from
      Toshiba Medical Systems Corp.

PMID- 28517656
TI  - SU-E-I-78: Neuromelanin in the Subthalamic Nucleus of Patients with Parkinson's
      Disease: An Electron Spin Resonance Spectroscopy Study.
AB  - PURPOSE: Parkinson disease and related syndromes are associated directly with the
      concentrations of neuromelanin, iron and other heavy metals, and nowadays it is
      discussed the possible protective role of neuromelanin by the sequester redox
      active iron ions, reducing the formation of free hydroxyl radicals and therefore
      inactivating the iron ions that induce oxidative stress. The aim of this work is
      to study the concentration ratios between iron ions and neuromelanin in
      subthalamic nucleus of patients with Parkinson's disease (PD) using Electron Spin
      Resonance (ESR). METHODS: Necropsy samples of subthalamic nucleus from eight
      human brains were studied: three non-affected by any neurodegenerative disease
      and five with Parkinson's disease. The samples were stored in formaldehyde and
      washed with a solution of 0.01 molar of ethylenediaminetetraacetic acid. ESR
      experiments were development in a JEOL FA-200 X-Band spectrometer at different
      temperatures between -170 degrees  C to room temperature. The relative
      concentrations of each species were estimated from the double integral values of
      the fitted spectra. RESULTS: For all samples, ESR spectra showed to be composed
      of three different signals following the Curie's law. One signal was attributed
      to high-spin ferric ions (g~ 4.3) in rhomboedric symmetry, Cu(II) ions (close to
      g=2.0) and neuromelanin (g~ 2.01). The ferric ions concentration ratio between
      patients and controls was 3.0+/-0.2. The same ratio for neuromelanine was 0.24+/
      0.06. CONCLUSIONS: Our preliminary results indicated a significant increment of
      iron concentration in PD samples which agrees with previous histochemical and
      biochemical reports. This finding and the clear reduction of neuromelanin
      concentration in PD samples suggest the possible role of neuromelanin as iron
      ions storage.

PMID- 28517657
TI  - SU-E-I-61: Phantom Design for Phase Contrast Breast Imaging.
AB  - PURPOSE: Phase contrast breast imaging has the potential to improve visualization
      of anatomic structures. While the physics is well-understood, there are several
      choices for implementation. In order to evaluate these choices, it is essential
      to design a phantom for phase contrast imaging with appropriate breast-equivalent
      materials. METHODS: Phantoms for mammography use materials that mimic the x-ray
      attenuation properties of breast tissue. Hence, the refractive index decrement
      (delta) was determined for breast tissues of varying glandular fraction
      [Hammerstein, Radiology 130(2):485-91, 1979] for the energy range (5-100 KeV)
      relevant to mammography and breast CT using XOP software (Version 2.3, ESRF,
      France) and compared to that of commonly used phantom materials. Delta for 50%
      and 70% glandular breast-equivalent material (CIRS Inc., Norfolk, VA), solid
      water, BR-12, polymethyl methacrylate (PMMA), beeswax (C46H92O2, density: 0.97
      g/cm3 ) and paraffin wax (C25H52, density: 0.95 g/cm3 ) were determined.
      Microcalcifications in vivo are either of oxalate or phosphate composition. Delta
      of calcium oxalate monohydrate (COM) and calcium hydroxyapatite (CH) were
      determined and compared with that of calcium carbonate, gold and aluminum.
      RESULTS: In terms of delta, paraffin wax (4% higher) and beeswax (4% higher) best
      simulated 50% and 100% glandular breast, respectively. Delta of other commonly
      used phantom materials such as 50% and 70% glandular breast-equivalent material,
      solid water, and BR-12 were two orders of magnitude higher, and that of PMMA was
      28% higher, than 50% glandular breast tissue. For microcalcifications, delta of
      gold was 4.6 to 6.5 times higher than that of COM and CH, respectively. Delta of
      aluminum and calcium carbonate were found to straddle that of COM and CH.
      CONCLUSIONS: For phase contrast imaging, a phantom comprising paraffin wax to
      simulate 50% glandular background tissue, beeswax to simulate a mass equivalent
      to 100% glandular tissue, and calcium carbonate or aluminum to simulate
      microcalcifications is appropriate. Supported in part by the National Institutes
      of Health (NIH) grants R01 CA128906 and R21 CA134129. The contents are solely the
      responsibility of the authors and do not represent the official views of the NIH
      or NCI.

PMID- 28517658
TI  - SU-E-I-71: Susceptibility Weighted Imaging (SWI) Software for Post-Processing of
      SWI Data.
AB  - PURPOSE: To develop open source software for post processing of susceptibility
      weighted (SWI) MR images using magnitude and phase data. METHODS: SWI data was
      acquired using Philips MRI 3T scanner with the following parameter: 3D T1 FFE
      axial with TR=40ms, TE=25ms, FOV=22 cm, acquisition matrix of 440*440 and 40
      slices. Both magnitude and phase data was stored for SWI post processing. The SWI
      homodyne filtering is performed by converting the magnitude and phase image to
      complex real and imaginary images. The SWI software was implemented in C++ using
      ITK (Image registration and segmentation toolkit) toolkit. To generate SWI maps
      the user needs to provide the DICOM data directory, the series number of DICOM
      SWI series, low pass filter size and the weighting factor of phase mask. This
      outputted SWI series is saved as DICOM and appended to the patient series and can
      be viewed in any DICOM compatible viewer. The software also outputs SWI filtered
      phase maps which can be further used for iron quantification in organs like
      brain, liver etc. RESULTS: An open source implementation of SWI post-processing
      tool using ITK was provided. The SWI processed phase weighted data can be used
      for qualitative assessment of iron deposits. The filtered phase map outputted can
      be used for quantitative iron measurements. CONCLUSIONS: SWI post processing
      software is implemented here to provide qualitative SWI maps of iron deposits in
      brain and other organs. The post processed images can also be useful for MR
      Venography with minimum intensity projection. This tool would be useful to study
      disease processes involved with accumulation of iron in different organs.

PMID- 28517659
TI  - SU-E-I-82: Image Signal-To-Noise Equalization in Whole Body PET Using Variable
      Acquisition Times.
AB  - PURPOSE: Whole Body PET scans are acquired at multiple axial positions, where the
      acquisition time at each position is constant. Although the acquisition time is
      adjusted for patient weight, the varying amount of attenuation and activity
      distribution for different sections, the image S/N can vary significantly. The
      aim of this work is to investigate the use of variable bed position scan times in
      WB-PET to equalize the Signal-to-Noise ratio in the axial direction. METHODS:
      Simulations of activity and attenuation distributions based on whole body CT
      scans were performed. Phantoms of different cross sections were also simulated
      and imaged. Image noise was estimated by generating multiple noise replicates by
      adding Poisson noise to the emission sinograms for the simulated images, and
      using a bootstrap method for the phantom patient measurements. By comparing the
      square of image noise (SD/Mean) for all the image slices, the acquisition time
      for each section could be adjusted to yield uniform image noise for all slices.
      The image noise was also compared to the average AC factors through the center of
      each body slice. RESULTS: A polynomial function was found for both simulations
      and the measurements to accurately describe image noise as a function of AC
      factors. Using this relationship, the acquisition time at each axial position can
      be adjusted to produce images of relatively uniform S/N, independent of cross
      sectional thickness. This was confirmed in phantom and patient data. CONCLUSIONS:
      The noise properties of WB-PET images can be equalized axially by adjusting the
      acquisition time according to the amount of attenuation. The acquisition time can
      be reduced in areas of lower attenuation and increased in more absorbing sections
      Since there is a correlation of the image noise and the CT-derived AC factors,
      the acquisition times can quickly calculated using a simple functional
      relationship.

PMID- 28517661
TI  - SU-E-I-114: Clinical Ultrasound Transducer Degradation Effects on the Accuracy of
      Spectral Doppler Velocity Measurements.
AB  - PURPOSE: Ultrasound Doppler velocity measurements are routinely used to determine
      the severity of a stenosis in the carotid, renal or peripheral arteries. The
      objective of this study is to investigate and demonstrate the relationship
      between Doppler velocity measurements and transducer degradation conditions
      encountered in a clinical environment. METHODS: Assessing transducer performance
      was accomplished using the First Call aPerio Test System transducer analyzer
      (Sonora Medical Systems, Longmont, CO). This system was used to conduct 1,145
      semi-annual transducer assessments at 7 clinical sites from September 2007 to
      February 2012 as part of a comprehensive quality control program. The results
      were evaluated to determine the degree of transducer degradation encountered in
      the clinical environment. A Siemens Acuson S2000 (Siemens AG, Erlangen, Germany)
      ultrasound system was employed with the 1425A LE Doppler Flow System (Gammex,
      Middleton, WI) to determine Doppler velocity measurements. A transducer fixation
      device was fabricated to provide accurate, repeatable velocity measurements.
      Transducers with the most severe degradation were evaluated by comparing velocity
      measurements to those without defects. Using several matched transducer pairs,
      simulated failure modes were tested. The Doppler measured time-average mean
      (TAMn) and time-average maximum (TAMx) velocities were obtained and reported.
      RESULTS: This investigation found that 4.5% of the transducers surveyed during
      this 5-year period of time failed at least one acceptance criteria. Many (346 or
      30%) had at least one defect. Typical findings include dead elements, lens
      delamination, wire cuts, and capacitance shorts. Only the most severe transducer
      defects and degradation conditions resulted in a noticeable deviation in the
      velocity measurements. Simulated transducer degradation testing confirmed this
      finding. CONCLUSIONS: The relationship between Doppler velocity measurements and
      transducer degradation conditions is limited, becoming significant for only the
      most severe degradation conditions. Based on our experience, this level of
      transducer degradation is rarely encountered in the clinical environment.

PMID- 28517662
TI  - SU-E-I-85: Evaluation of a Solid-State Dosimeter Module for Measuring Nuclear
      Medicine Radionuclides.
AB  - PURPOSE: A recently introduced solid-state dosimeter module (UDOS001, Teledyne
      Microelectronic Technologies, Los Angeles, CA) requires only external power
      (e.g., from two nine-volt batteries in series) and a battery- powered data
      recorder to assemble a compact, portable dosimeter. This device was developed for
      radiation detection and monitoring of a wide range of radiation types. It has a
      nominal minimum energy of 100 keV. The present study sought to determine its
      suitability for measuring the dose from radionuclides used in nuclear medicine.
      METHODS: Three radionuclides (initially 4.77 mCi of F-18, 3.86 mCi of I-131, and
      12.4 mCi of Tc-99m) were measured at a distance of one meter and at several
      different angles of incidence. The most sensitive analog output of the dosimeter
      was digitized by a battery-powered data logging device (Track-It 5VDC, Monarch
      Instrument, Amherst NH). These data were transferred from the data logger into a
      Windows 7 personal computer, formatted as an Excel 2010 spreadsheet and converted
      from voltage to dose using the manufacturer's nominal calibration factor of 14
      urad/19.5 mV step. The dose rate was determined from the slope of a linear fit to
      the cumulated dose as a function of time. RESULTS: The nominal calibration of the
      dosimeter gives dose rate measurements that are close to published gamma ray dose
      rate constants for these radionuclides (0.65 vs. 0.70, 0.25 vs. 0.28, and 0.071
      vs. 0.078 mrad/mCi-hr respectively). The angular dependence of the response is
      greater at 140 keV than at 511 keV, but an acceptance angle of at least 90
      degrees has uniform response with all three radionuclides. CONCLUSIONS: A better
      calibration factor would be 0.154 urad/19.5 mV step at these gamma ray energies.
      This dosimeter can be used to measure the dose from common radionuclides used in
      nuclear medicine.

PMID- 28517660
TI  - SU-E-I-103: Detecting Anomalous Pixels and Correlated Artifacts in Digital
      Detectors from Flat-Field Images.
AB  - PURPOSE: Anomalous pixels may be defined as those pixels whose exposure response
      relationship is deviant from the typical, expected or calibrated response. A
      group of anomalous pixels may Result in visible correlated artifacts. Here we
      demonstrate an approach to identify anomalous pixels and correlated artifacts
      using flat-field images. METHODS: Using manufacturer specific calibration
      geometry, sets of four flat-field images per detector were obtained with varying
      input air kerma values (0.5 to 160 MUGy) from 9 digital detectors at 6
      institutions. Images obtained before and after calibration, with both proper and
      improper gain maps and structured artifacts were additionally acquired with some
      detectors. Image analysis methodology under consideration by AAPM Task Group 150
      was used.After eliminating 10mm borders, images were divided into square regions
      (100mm2 ). Anomalous pixels were identified as pixels within each region with
      valuesabove or below +/-3 standard deviations (SD) relative to the mean value of
      the region. If these pixels were identified in all four images comprising a set,
      then they were reported as anomalous. Line artifacts were identified as rows and
      columns with cumulative profile values that were above or below +/-3 SD with
      respect to the mean value of neighboring profiles in the set of four flat-field
      mages. Results were verified with visual inspection of the images. RESULTS: For
      four sets of images, the algorithm did not identify any anomalous pixels, and
      none were spotted on visible inspection as well, while for five sets of images
      the identified anomalous pixels matched visual inspection results. Anomalous
      pixel detection failed in regions with an unusually large number of defects and
      structured noise, since those regions exhibited relatively large SD. Line
      artifacts consistent with visual analysis were identified correctly when present.
      CONCLUSIONS: A practical approach to identify anomalous pixels and correlated
      artifacts from flat-field images is demonstrated.

PMID- 28517664
TI  - SU-E-I-107: Suitability of Various Radiation Detectors Used in Radiation Therapy
      for X-Ray Dosimetry in Computed Tomography.
AB  - PURPOSE: Assessment of suitability for X-ray dosimetry in computed tomography of
      various ionization chambers, diodes and two-dimensional detector arrays primarily
      used in radiation therapy. METHODS: An Oldelft X-ray simulation unit was used to
      irradiate PTW 60008, 60012 dosimetry diodes, PTW 23332, 31013, 31010, 31006 axial
      symmetrical ionization chambers, PTW 23343, 34001 plane parallel ionization
      chambers and PTW Starcheck and 2D-Array seven29 as well as a prototype Farmer
      chamber with a copper wall. Peak potential was varied from 50 kV up to 125 kV and
      beam qualities were quantified through half-value-layer measurements. Energy
      response was investigated free in air as well as in 2 cm depth in a solid water
      phantom and refers to a manufacturer calibrated PTW 60004 diode for kV-dosimetry.
      RESULTS: The thimble ionization chambers PTW 31010, 31013, the uncapsuled diode
      PTW 60012 and the PTW 2D-Array seven29 exhibit an energy response deviation in
      the investigated energy region of approximately 10% or lower thus proving good
      usability in X-ray dosimetry if higher spatial resolution is needed or rotational
      irradiations occur. CONCLUSIONS: It could be shown that in radiation therapy
      routinely used detectors are usable in a much lower energy region. The rotational
      symmetry is of advantage in computed tomography dosimetry and enables dose
      profile as well as point dose measurements in a suitable phantom for estimation
      of organ doses. Additional the PTW 2D-Array seven29 can give a quick overview of
      radiation fields in non-rotating tasks.

PMID- 28517663
TI  - SU-E-I-96: Realistic Synthetic CT Imaging of Small Numerical Lesions with Simple
      CT Simulation Model Incorporating Equipment MTF.
AB  - PURPOSE: Quantitative analysis in CT imaging often requires image data set of
      lesions with ground truth, which is practically impossible in general. This study
      presents a simple CT simulation model which enables to create realistic synthetic
      CT images of numerical voxel phantoms for small lesionswith various shape and
      sizes. METHODS: Basic CT parameters were acquired from DICOM header of target CT
      data, and were used in the CT simulator. Frequency response of forward and
      backward projectors were determined by measuring NPS of reconstructed image from
      white Gaussian noise input data, which were then used to iteratively calibrate
      those projectors so as to produce white Gaussian NPS output. Then, the MTF of
      target equipment were measured and incorporated into the sinogram filter before
      back projection in order to reflect focal spot blurring and vendor specific recon
      kernel. For validation, physical and numerical phantoms with rod and tube shape
      of 2mm ~ 10mm were created and imaged with a real CT (Sensation 16, Siemens) and
      the proposed simulated CT, respectively. Images were reconstructed with 8
      different kernels (B10 ~ B80) in both CT imaging technique, and their line
      profiles were compared. RESULTS: Synthesized and physically scanned CT images of
      phantoms with different shape, sizes, and recon kernels agreed well in visual
      assessment, size measurement, and line profile comparison. CONCLUSION: Proposed
      method could produce realistic synthetic CT images of numerical phantoms highly
      mimicking in visual appearance and quantitative comparison, which has a potential
      for use as ground truth data set in quantitative image analysis.

PMID- 28517666
TI  - SU-E-I-89: Applying Image Gently and Image Wisely in Nuclear Medicine.
AB  - PURPOSE: To demonstrate how principles and recommendations of the Image Gently(r)
      and Image WiselyTM campaigns can be clinically implemented. METHODS:
      Implementation of Image Gently(r) and Image WiselyTM guidelines was a quality and
      safety improvement project for our Nuclear Medicine department in 2011. Pediatric
      administered radiopharmaceutical doses were compared to recommended doses in the
      North American Consensus Guidelines for AdministeredRadiopharmaceutical
      Activities in Children and Adolescents and the European Association of Nuclear
      Medicine Paediatric Dose Card. Adult administered radiopharmaceutical doses were
      compared to administered doses in NCRP Report No. 160 and IAEA Report No. 40.
      RESULTS: Evaluation of site administered radiopharmaceutical doses showed that
      nearly all doses were comparable to those recommended by national and
      international advisory bodies. Administered doses for the pediatric renogram and
      the adult gastric emptying were adjusted to match the recommendations and
      resultant image quality evaluated. CONCLUSIONS: Radiation dose from nuclear
      medicine procedures should not be overlooked in the focus on CT dose reduction.
      An estimated 19.7 million nuclear medicine procedures are done annually in the
      U.S., with doses comparable to that from CT scans. Nuclear medicine departments
      should evaluate their pediatric administeredradiopharmaceutical doses against the
      North American Consensus Guidelines for Administered Radiopharmaceutical
      Activities in Children and Adolescents and evaluate their adult doses against
      national and international standards. Administered doses that are not comparable
      to the recommended values should be adjusted accordingly. Additional steps to
      reduce patient radiation dose include decision support to reduce inappropriate
      ordering, technique optimization for the CT scan portion of SPECT/CT and PET/CT,
      use of vendor's dose reduction camera and software technology, use of shorter
      lived radiopharmaceuticals, and 'right sizing' patient doses by weight.

PMID- 28517665
TI  - SU-E-I-73: Gray Matter Atrophy and White Matter Tract Abnormalities by Voxel Wise
      Correlation Analysis in Patients with Alzheimer's Disease.
AB  - PURPOSE: We evaluated the relationship between white matter (WM) tract
      disintegration and gray matter (GM) atrophy in patients with Alzheimer's disease
      (AD), mild cognitive impairment (MCI) and controls, using diffusion tensor
      imaging (DTI) and an optimized voxel-based analysis. METHODS: Two hundred thirty
      one individuals (61 controls, 116 MCI and 54 AD) were included. Voxel-based WM
      tract statistics was used to obtain whole-brain maps of WM bundles for FA. Voxel
      based morphometry (VBM) was conducted to detect regions of gray matter (GM)
      atrophy in the AD, MCI group relative to the control group. FA maps were
      processed to make voxel-wise comparison of tract based analysis in whole brain
      between each the two groups. The relationship between locations of abnormalities
      in the WM and GM were examined. RESULTS: Patients with AD showed significant GM
      atrophy in posterior cingulate gyrus (BA31, 32) to the precuneus, the middle
      temporal lobe (BA19), the superior frontal (BA9) to the anterior cingulate (BA
      32), the medial frontal lobe (BA 11, BA25), the hippocampus, the parahippocampal
      gyrus (BA30/34) and the insula, and WM tract disintegrity of the uncinate
      fasciculus, posterior cingulate fasciculus and fornix compared with the control
      and MCI groups. These abnormalities in the AD group were caused by either
      structural changes in GM atrophy or neural dysfunction due to functional
      disconnections in the WM tract. CONCLUSIONS: The GM atrophy resulting from WM
      tract disintegration or GM atrophy itself may be the first step in the AD
      process, resulting in anatomically congruent correlations between WM
      disintegration and regional GM atrophy. Using tract based spatial statistics and
      voxel based analysis, both of which are useful in investigating GM and WM changes
      in individuals with neurodegenerative disorders.

PMID- 28517667
TI  - SU-E-I-100: Feasibility Study of Gamma-Ray Medical Radiography.
AB  - PURPOSE: The purpose of this research is to study an alternative technique to
      conventional x-ray radiography that requires less patient radiation dose, less
      cost, portable, requires less maintenance, and less power consumption. This
      research explores the feasibility of using gamma-ray radiography in medical
      imaging. Gamma-ray medical radiography has the potential to provide alternative
      diagnostic medical information to X-ray radiography. METHODS: Approximately one
      Ci of Am-241 radioactive source which emits monoenergetic 59.5 KeV gamma rays was
      used in this study. Several factors that influence this feasibility were studied.
      These were the radiation source uniformity, image uniformity, image quality
      parameters such as contrast, noise, and spatial resolution. In addition, visual
      assessment of several human phantom gamma-ray and x-ray images were conducted.
      The images were recorded on computed radiography image receptors and displayed on
      a standard monitor. RESULTS: The radioactive source provided a relatively uniform
      radiation exposure and uniform images. Image noise was mainly dependent on the
      exposure time and the source size. Although the contrast depended on the window
      and level setting, it was also dependent on the exposure time and the source
      size. Spatial resolution was dependent on the source size and the magnification.
      The generated gamma-ray images were of lower quality than the X-ray images which
      was mainly due to the low radioactivity used. However, the gamma-ray images
      displayed most of the main structures contained in the humanoid phantoms.
      CONCLUSIONS: Thisresearch explored the feasibility of using gamma-ray radiography
      in medical imaging and showed that gamma-ray medical radiography has the
      potential to provide alternative diagnostic medical information to X-ray
      radiography. Finally, this research also paves the way for the usage and
      production of high radioactive Am-241 source that will show high quality medical
      gamma-ray radiography is feasible.

PMID- 28517669
TI  - SU-E-I-111: Evaluation of the Analytical Scattering Models of 1) Lynch-Dahl 2)
      Highland and 3) Rossi for Proton Beams and Comparison with GEANT4 Monte Carlo
      Simulations as a Prerequisite for Proton Radiography Applications for Patients.
AB  - PURPOSE: To evaluate the approximate 1) Lynch-Dahl 2) Highland and 3) Rossi
      scattering models for proton beams with GEANT4 Monte Carlo. This is a
      prerequisite for proton radiography applications for patients. METHODS: A Matlab
      program developed in-house at MGH was used to obtain a semianalytical generalized
      Fermi-Eyges theory estimation of the spatial and angular spreads of a 230 MeV
      zero-spread incident proton beam as a function of depth. The constants of 1)
      Lynch-Dahl 2) Highland and 3) Rossi were used respectively for each model. MC
      simulations will determine which approximation provides the best prediction for
      different media configurations. Further, the calculated spreads were used to
      inform proton radiography imaging by calculating two limiting angles, a
      positional Acut and a directional Ccut. Acut is defined as the viewing angle of a
      point of incidence observer at which they see a point displaced by one positional
      standard deviation. Ccut is defined as the direction cosine of one angular
      standard deviation momenta. RESULTS: Both the angular and spatial spreads as well
      as their respective model differences rose monotonically with depth in water. At
      30 cm depth the angular spread reached values around 3 degrees with about 0.32
      degrees model difference, translating to Ccut differences in the first or second
      significant digit. At the same depth the spatial spread reached values around 1.2
      cm with about 0.7 mm model difference, translating to Acut differences in the
      first or second significant digit. Preliminary MC data (not shown) indicate that
      the signals obtained due to the influence of inhomogeneities are small and the
      model differences may be relevant. CONCLUSIONS: We observed non-negligible
      differences between the models using MC. Further analysis is required to
      understand, which model provides most accurate scattering predictions for protons
      penetrating different media configurations.

PMID- 28517668
TI  - SU-E-I-67: Multi-Shot RESOLVE Compared to Single-Shot EPI Diffusion- Weighted MR
      Imaging Acquisition Scheme.
AB  - PURPOSE: The purpose of this project was to configure the parameters for optimal
      comparison of image quality differences between the prototype imaging technique,
      read-out-segmented EPI multi-shot (RESOLVE) and the clinically used single-shot
      EPI (SS-EPI) MRI sequence for Diffusion Weighted Imaging (DWI) in a saline
      phantom, followed by a normal rat brain. METHODS: Saline phantom (4.2 * 4.2 cm2 )
      and a rat brain were imaged on the 1.5T ESPREE (Siemens, Germany) MRI magnet
      using a wrist coil. Both the SS-EPI and RESOLVE DWI were optimized with equal
      imaging parameters such as slice thickness/slice gap = 3.0/0 mm, field of view =
      210 mm, phase resolution = 100%, and diffusion b values = 0, 600 s/mm2 while
      other parameters were given similar settings such as the base resolution, which
      had to be interpolated for the SS-EPI to 96i to match the RESOLVE as it was
      unable to be set at 192. Image quality was compared in terms of signal intensity,
      distortion, % ghosting and Apparent Diffusion Co-efficient (ADC) measurements
      from each sequence. RESULTS: A marked enhancement of overall image quality with
      superior detail was observed in each of the scans from the RESOLVE sequence when
      compared to the SS-EPI. Comparing the efficiency of both sequences in terms of
      image quality, RESOLVE demonstrated a better stable image with minimal distortion
      and ghosting. The phantom dimensions obtained from RESOLVE images matched the
      actual dimensions perfectly. RESOLVE images had signal intensities significantly
      higher than (2.4*) the SS-EPI images (p=0.0008) and ~0.6 % times less ghosting
      compared to SS-EPI (p=0.82) which also exhibited distortion with reduced phantom
      dimensions (4.05 * 3.28 cm) from original. The ADC values computed were almost
      identical to be (p=0.32) from SS-EPI (2.21mm2 /sec) and RESOLVE (2.19mm2 /sec).
      CONCLUSIONS: The RESOLVE sequence has significantly superior image quality
      compared to SS-EPI at 1.5 T with reasonable scan times. DWI with RESLOVE
      acquisition scheme can be highly beneficial in obtaining distortion free images
      in routine clinical studies to characterize tumors and other pathological
      mechanisms with much greater detail than the current clinically used SS-EPI.

PMID- 28517670
TI  - SU-E-I-77: X-Ray Coherent Scatter Diffraction Pattern Modeling in GEANT4.
AB  - PURPOSE: To model X-ray coherent scatter diffraction patterns in GEANT4 for
      simulating experiments involving material detection through diffraction pattern
      measurement. Although coherent scatter cross-sections are modeled accurately in
      GEANT4, diffraction patterns for crystalline materials are not yet included. Here
      we describe our modeling of crystalline diffraction patterns in GEANT4 for
      specific materials and the validation of the results against experimentally
      measured data. METHODS: Coherent scatter in GEANT4 is currently based on
      Hubbell's non-relativistic form factor tabulations from EPDL97. We modified the
      form-factors by introducing an interference function that accounts for the
      angular dependence between the Rayleigh-scattered photons and the photon
      wavelength. The modified form factors were used to replace the inherent form
      factors in GEANT4. The simulation was tested using monochromatic and
      polychromatic x-ray beams (separately) incident on objects containing one or more
      elements with modified form-factors. The simulation results were compared against
      the experimentally measured diffraction images of corresponding objects using an
      in-house x-ray diffraction imager for validation. The comparison was made using
      the following metrics: number of diffraction rings, radial distance, absolute
      intensity, and relative intensity. RESULTS: Sharp diffraction pattern rings were
      observed in the monochromatic simulations at locations consistent with the
      angular dependence of the photon wavelength. In the polychromatic simulations,
      the diffraction patterns exhibited a radial blur consistent with the energy
      spread of the polychromatic spectrum. The simulated and experimentally measured
      patterns showed identical numbers of rings with close agreement in radial
      distance, absolute and relative intensities (barring statistical fluctuations).
      No significant change was observed in the execution time of the simulations.
      CONCLUSIONS: This work demonstrates the ability to model coherent scatter
      diffraction in GEANT4 in an accurate and efficient manner without compromising
      the accuracy or runtime of the simulation. This work was supported by the
      Department of Homeland Security under grant DHS (BAA 10-01 F075), and by the
      Department of Defense under award W81XWH-09-1-0066.

PMID- 28517671
TI  - SU-E-I-60: Validation of An Optically Stimulated Luminescent (OSL) Dosimeter for
      Use in Output Exposure Control Verification of Mammography Imaging Systems.
AB  - PURPOSE: To develop and validate an Optically Stimulated Luminescent (OSL)
      dosimeter for exposure control verification of x-ray projection mammography
      imaging systems. METHODS: The active detection element of the dosimeter is a
      strip of OSL material 3.0 mm wide, 0.13 mm thick and 30.0 mm long with an
      overlying aluminum step wedge with thicknesses of 0, 0.2, 0.4 and 0.6 mm Al,
      encapsulated in a light-tight plastic enclosure with outer dimensions of 10.0 mm
      wide, 5.4 mm thick, and 54.0 mm long. The dosimeter is used in conjunction with a
      breast phantom for the purpose of estimating the half-value layer (HVL), entrance
      surface exposure (ESE), and average glandular dose (AGD) in conventional
      projection mammography. ESE and HVL were computed based on analysis of exposure
      profiles obtained from exposed strip dosimeters. The AGD was estimated by
      multiplying the ESE by the appropriate exposure to dose conversion factor for the
      thickness and % glandular tissue fraction represented by the phantom and target
      filter combination employed. The accuracy and reproducibility of the ESE, HVL and
      AGD estimates obtained using the dosimeter positioned on the surface of the ACR
      phantom at the chest wall edge, was evaluated using mammography systems utilizing
      different imaging receptor technology, i.e. screen-film (SF), computed
      radiography (CR) and direct radiography (DR) and compared against results
      obtained using a calibrated ion chamber fitted with a mammography probe. RESULTS:
      ESE, AGD and HVL results obtained using the OSL mammography QA dosimeter agreed
      with results obtained using an ion chamber to within 5-10%, depending on the
      target-filter combination used. Repeat readings were highly consistent with a
      coefficient of variation = 5%. CONCLUSIONS: The OSL mammography QA dosimeter has
      been shown to effectively estimate ESE, HVL and AGD, demonstrating its usefulness
      for secondary monitoring of output exposure of mammography imaging systems.

PMID- 28517672
TI  - SU-E-I-81: Toward in Vivo Magnetic Spectroscopy of Brownian Motion.
AB  - PURPOSE: Magnetic spectroscopy of Brownian motion (MSB) has been used previously
      to measure temperature, viscosity, and cellular binding in vitro. The MSB signal 
      a ratio of the 5th to 3rd harmonic of the response from magnetic nanoparticles
      to an oscillating field - provides insight into particle microenvironment. These
      biosensing capabilities would be productive in vivo but until now were prevented
      by sensitivity limits. Our goal was to design and create a similar apparatus for
      work in vivo. In vivo spectroscopy is a viable precursor to imaging, and is
      essential for drug delivery or therapeutic methods like hyperthermia. METHODS:
      Coil geometries were modeled to optimize a uniform Helmholtz drive coil and
      imaging coil with maximal spatial resolution. The completed apparatus includes
      balancing and trim coils to zero out unwanted background fields. The coils were
      characterized and experiments were performed to verify consistency with previous
      in vitro experiments. Finally, as an in vivo experiment, we took MSB spectra on
      living mice with five week old melanomas injected with 200ug of 100nm starch
      coated nanoparticles. RESULTS: The drive coil is capable of sustaining 12.5mT
      fields up to 1.5kHz with a field variation of 3% throughout the sample volume.
      The pickup coil is frequency independent and has a vertical and horizontal range
      of 5mm and 10mm respectively before the MSB signal drops below 50%. The minimum
      sensitivity is 50-70MUg of iron. MSB signal response to viscosity changes shows
      the same signatures as the in vitro apparatus. The in vivo data showed successful
      sensing of nanoparticles. We also saw the MSB signal decay with time showing the
      apparatus can detect changes in particle behavior due to interactions with
      biology. CONCLUSIONS: We achieved in vivo MSB and due to sufficient sensitivity
      we are motivated to further work in monitoring in vivo cellular uptake and
      viscosity.

PMID- 28517732
TI  - T-cells and macrophages peak weeks after experimental stroke: Spatial and
      temporal characteristics.
AB  - The activities of the central and peripheral immune systems impact neurological
      outcome after ischemic stroke. However, studies investigating the temporal
      profile of leukocyte infiltration, especially T-cell recruitment, are sparse. Our
      aim was to investigate leukocyte infiltration at different time points after
      experimental stroke in mice. Permanent middle cerebral artery occlusion was
      performed on 11 weeks old C57BL/6J mice, allowed to survive for 1, 3, 8, 14 or 28
      days. In addition to infarct size measurements, detailed immunohistochemical
      analyses of T-cell and macrophage influx were performed. A recently introduced F
      19 MR probe (V-sense), designed to track macrophages, was furthermore tested.
      Fourteen and 28 days after permanent middle cerebral artery occlusion a
      significant increase in CD3+ T-cells was found within the ipsilateral hemisphere
      compared to controls, especially within the infarct core and the corpus callosum.
      The number of CD68+ cells within the infarct core was significantly increased at
      days 8, 14 and 28. This temporal pattern was also seen in MRI. After experimental
      stroke within the infarcted cortex we found a delayed (day 14) infiltration of T
      cells and macrophages. Furthermore, our data show that T-cells are present in
      higher numbers in the corpus callosum compared to the rest of the brain (except
      from the infarct core where they were highest).

PMID- 28517793
TI  - SU-E-T-170: A Viable Approach to Patient Specific QA for Spine VMAT SRS Using
      EPID-Based Dosimetry.
AB  - PURPOSE: VMAT involves multi-parameter modulations, thus presenting multi
      dimensional challenges. Here, we present a viable approach to VMAT patient
      specific QA using EPID-based dosimetry for spine VMAT SRS casesMethods: Our spine
      VMAT SRS plans consisted of two full arcs and were optimized with 6 MV photons
      for a Varian Trilogy LINAC. The QA plans were computed by resetting all control
      points to 0 degrees  gantry angle while keeping the MLC apertures and
      corresponding MU weights intact. The dose distribution at the depth of clinical
      significance was calculated in a solid water phantom. EPIDose (Sun Nuclear Corp)
      was used to convert MV EPID images into absolute dose in a plane of interest in a
      homogeneous medium. During measurements, the source-to-detector distance (SDD)
      was set to 105 cm and the VMAT QA plan was delivered with 600 MU/min. For each QA
      plan, three measurements were made. The average pass rate (thresholds: 2%/2 mm)
      was then calculated. In addition, the dose at the isocenter or other points of
      clinical significance was also measured and the mean was calculated. RESULTS: Our
      current institutional QA acceptance criteria for VMAT plans are: pass rate 90%
      for 2%/2mm with a dose threshold of 10% and the discrepancy between the measured
      and planned doses at the isocenter or other points of clinical significance 2%.
      Our preliminary investigation indicated that the pass rate was normally greater
      than 95.0% with a total number of valid detection points of ~30000. The dose
      difference at the point of interest was, in general, around +/-1.0 %. Sharp dose
      gradients were accurately detected at the PTV-cord interface. CONCLUSIONS: EPID-
      based dosimetry is real-time and financially viable. It can achieve sub-
      millimeter dosimetry accuracy without extensive inter-diode interpolations. We
      believe that EPID-based VMAT dosimetry offers a competitive alternative to other
      competing dosimetry technologies.

PMID- 28517794
TI  - SU-E-T-180: The Radiological Physics Center's Anthropomorphic Quality Assurance
      Phantom Program.
AB  - PURPOSE: To describe the phantoms, program logistics and current results for the
      Radiological Physics Center's (RPC) anthropomorphic QA phantom program for
      credentialing institutions for participation in NCI-sponsored advanced technology
      clinical trials. METHODS: The RPC has developed an extensive phantom
      credentialing program consisting of four different phantoms designs: H&N, pelvis,
      lung and spine. These QA phantoms are water-filled plastic shells with imageable
      targets, avoidance structures, and heterogeneities that contain TLD and
      radiochromic film dosimeters. Institutions wishing to be credentialed request a
      phantom and are prioritized for delivery. At the institution, the phantom is
      imaged, a treatment plan is developed, the phantom is positioned on the treatment
      couch and the treatment is delivered. The phantom is returned and the measured
      dose distributions are compared to the institution's electronically submitted
      treatment plan dosimetry data. RESULTS: The RPC currently has an inventory of 31
      H&N, 10 pelvis, 9 lung, and 8 spine phantoms that are mailed to institutions
      nationally and internationally. In 2011, 444 of these phantoms were mailed out
      for credentialing. Once the phantom is sent, it takes the institution an average
      of 26 days to return it to the RPC. On average the dosimeters are analyzed within
      17 days and the report is sent 21 days after receipt of the phantom data. In 2011
      the percent of phantoms meeting the acceptance criteria increased by 12, 13 and 6
      percentage points for the H&N, spine and lung phantoms, respectively. It fell by
      5 percentage points for the pelvis phantom. CONCLUSIONS: The RPC's QA phantom
      program has been an effective and responsive QA tool for assessing the use of
      advanced technologies in NCI sponsored clinical trials. The RPC has been
      efficient in its mailing of phantoms, and analyzing and reporting results. Work
      supported by PHS grant CA10953 and CA081647 (NCI, DHHS).

PMID- 28517733
TI  - Comparison of the measuring efficacy of transepidermal water loss of a reasonably
      priced, portable closed-chamber system device H4500 with that of rather
      expensive, conventional devices such as Tewameter(r) and Vapometer(r).
AB  - BACKGROUND/PURPOSE: Although measuring transepidermal water loss (TEWL) is
      important to assess the barrier function of the stratum corneum (SC), the
      commercially available instruments are rather expensive. Recently launched Model
      H4500 employs a closed-chamber system to measure TEWL and is more reasonably
      priced compared to devices currently in general use. METHODS: To check the
      reproducibility of the obtained data with H4500, we conducted measurements on the
      volar forearms of healthy volunteers and compared these data with those measured
      with Vapometer(r) and Tewameter(r) . Then, we checked the correlations between
      the TEWL data obtained with these different devices on the same volar forearms of
      15 healthy volunteers before and after the artificial production of barrier
      damage of the SC by tape stripping or by 0.5% aqueous solution of sodium lauryl
      sulfate. RESULTS: The obtained intra-class correlation coefficient (ICC, [1, 1])
      with 95% CI of H4500 was 0.927 (0.835-0.978). Namely, an excellent correlation
      could be found in the values of TEWL measured with these three different
      instruments not only on healthy skin but also on the artificially barrier-damaged
      skin. CONCLUSIONS: H4500 is considered to be practical for daily use because of
      its performance as well as its reasonable price as compared with conventional
      devices.

PMID- 28517795
TI  - SU-E-T-172: Ion Recombination Correction Factor in Medium Dose Rate for Advanced
      Markus Ionization Chamber.
AB  - PURPOSE: To determine the ion recombination correction factor using different
      methods in medium dose per pulse electron beams for Advance Markus ionization
      chamber (AMC) Methods: Two different methods were applied to obtain ion
      recombination correction factor. Conventional Boag's two voltage analysis (TVA)
      recommended in IAEA TRS-398 dosimetry protocol and recently modified Boag's TVA
      expressions which consider the effect of free electron contribution on ks value.
      High energy electron beams of a dedicated linear accelerator, NOCAC7 (NRT,
      Italy), for intraoperative radiation therapy were applied. Dose per pulse in
      medium range of 4 to 41 mGy/pulse was investigated. Radiochromic films (ISP
      Gafchromic EBT2, USA) have been exploited as reference dose rate independent
      method. Dose measurement was performed by AMC in a small water phantom (IBA
      Dosimetry, Germany). RESULTS: At reference conditions (9 MeV, 100 mm applicator,
      SSD 80 cm (27 mGy/pulse)), ks values derived from IAEA TRS- 398 dosimetry
      protocols deviates 0.3% from reference value. From 4-35 mGy/pulse TVA yielded
      acceptable result (in average 1.0% deviation). For dose rate more that 35
      mGy/pulse, conventional two voltage analysis (TVA) might be applied with caution
      (4.2% deviation at 41 mGy/pulse). In this range first model in the new modified
      Boag's expressions yielded acceptable accordance (average deviation 1.3%) in
      comparison with dose rate independent reference dosimeter (EBT2, Gafchromic
      film). The deviation in ks value among Boag's modified expressions increased when
      the dose rate raised. CONCLUSIONS: Authors concluded that AMC could be employed
      for absorbed dose determination of medium dose per pulse electron beams. The
      accuracy of TVA which is recommended currently in dosimetry protocol IAEA-TRS-398
      is dependent on the range of applied dose rate. It is proper to be used for dose
      rate less than 35 mGy/pulse. First expression in Boag's modified formulas is
      proper for ks determination in high dose rate values (> 35 mGy/pulse).

PMID- 28517796
TI  - SU-E-T-182: Delivery Verification of Tomotherapy Treatments Using Exit Detector
      Sinograms: A Phantom Study.
AB  - PURPOSE: The objective of this study was to use a liquid water female body
      phantom to investigate the feasibility of using helical Tomotherapy's exit
      detector data sinograms (EDDS) for quality assurance of Tomotherapy treatments.
      METHODS: Delivery Verification software (DV-Tool), described by Kapatoes et al.,
      uses EDDS and daily mega-voltage-CT images for delivery sinogram reconstruction
      and subsequent dose computations. These dose distributions should reflect
      variations in patient's anatomy and machine delivery. Phantom was used to verify
      the robustness of the DV-Tool for machine consistency over 2months, and
      sensitivity to weight loss and setup errors. Weight loss simulations were done by
      removing layers of bolus from the phantom's pelvis. Setup errors were simulated
      by performing known table shifts before the treatment. Two treatment plans
      simulating a breast and gynecological treatment plans were used for these
      evaluations. Reconstructed doses and dose volume histograms (DVHs) were analyzed
      in comparison to the plan DVHs by scaling the reconstructed PTV mean dose (PTV
      MD) to match the plan. PTV-MD differences before and after machine output
      adjustments were evaluated. RESULTS: Machine consistency check of gynecological
      plan revealed that the deviations were greater (+/-5%) during the week prior to
      target replacement. After output adjustments, the deviations for breast and
      gynecological plans agreed within +/-1.0% and +/-2.5%, respectively. Weight loss
      on the gynecological plan showed a correlation (R2=0.998) between lost thickness
      and increasing PTV-MD by approximately 5%/cm. Setup errors on the breast plan
      showed broadening shoulder of the PTV DVH for shifts greater than 5mm. Volume at
      20Gy for the right lung increased by 6% for 10mm shifts in both x and z
      directions. CONCLUSIONS: The DV-Tool is sensitive to simulated weight loss, setup
      errors, and machine output. Exit detector data and the DV-Tool have great
      potential for monitoring patient's delivered treatments. However, clinical
      workflow needs to be established.

PMID- 28517797
TI  - SU-E-T-154: Online Dose Verification with Gafchromic Film for Fixed-Gantry and
      Rotational Intensity Modulated Radiation Therapy: A Phantom Study.
AB  - PURPOSE: The patient specific quality assurance (QA) measurements for fixed
      gantry and rotational intensity modulated radiation therapy (IMRT and
      VMAT/RapidArc) are usually performed on a homogeneous phantom prior to the
      treatment. The purpose of this study is to develop an online method to verify the
      delivered dose to the patient on the treatment day. METHODS: An anthropomorphic
      (Rando) head phantom was immobilized in treatment position with a thermoplastic
      mask to simulate a real patient. A sheet of gafchromic film (EBT2) was sandwiched
      between a 1-cm-thick solid water slab, which was fixed to the Type-S extension
      board, and the patient's head hold (a pillow used here). The CT images of the
      Rando phantom were acquired and exported to the treatment planning systems. One
      step-and-shot fixed-gantry IMRT plan and one RapidArc plan were generated and the
      dose distributions on the film plane were calculated. The two plans were
      delivered to the patient (Rando phantom in this study) in the treatment position
      on a Varian Trilogy linear accelerator with two new films. The films were
      scanned, and the measurements were compared with the planned doses. RESULTS: The
      composite dose distributions measured on the film plane were the actual delivered
      dose for the treatment. The comparison between the measurement and planned dose
      profiles shows an agreement within 3% because of the good reproducibility of
      phantom positioning. Gamma pass rates (using 3mm and 3% criteria) for the IMRT
      and RapidArc plan were found to be 95% and 94%, respectively. CONCLUSIONS: The
      phantom study has demonstrated the feasibility of using gafchromic film for
      online dose verification. This simple method takes into account the patient
      heterogeneity and the treatment associated uncertainties such as setup error,
      intrafraction motions and machine related variations. It can be implemented as an
      online physics and/or clinical QA tool without taking additional machine time.

PMID- 28517798
TI  - SU-E-T-193: Using Truebeam's Research Mode to Automate Mechanical Quality
      Assurance.
AB  - PURPOSE: To determine the feasibility of automating mechanical quality assurance
      measurements on the Varian Truebeam LINAC. METHODS: Using the XML coding
      capability of the Varian Truebeam Research Mode, the LINAC was programmed to
      mimic the beams delivered for the following mechanical tests. These tests
      included: Field size accuracy, jaw positions for asymmetric fields, collimator
      rotation isocenter, and MLC positional-accuracy. Images for these beams were
      acquired with the EPID. The images were analyzed using an analysis code written
      in MATLAB. Tests for gantry and couch rotation isocenters and radiation and
      mechanical isocenter coincidence are being developed. RESULTS: For field-sizes
      ranging from 4*4cm2 to 15*15cm2 , the measured matched the nominal field sizes to
      within 1mm. The collimator rotation isocenter and the overall accuracy for
      asymmetric field matched to within 1mm. No positional error >1mm was seen in the
      33 MLC pairs visible in the MLC positional-accuracy images. CONCLUSIONS: A large
      portion of the time required to make mechanical QA measurements using film is
      spent placing, processing, and scanning the film. Complete automation in
      performing these mechanical tests results in a significant time gain compared to
      film. A majority of the mechanical tests suggested by TG-142 have been performed
      using this technique, and an automated mechanical QA process has been established
      in our clinic.

PMID- 28517799
TI  - SU-E-T-165: Protocol for Simplified Radiochromic Film Dosimetry.
AB  - PURPOSE: Radiochromic film provides dose measurement at high spatial resolution,
      but often is not selected for routine evaluation of patient-specific IMRT plans
      owing to ease-of-use factors. We have developed a simplified protocol that avoids
      complications encountered in commonly used methods. METHODS: We evaluated the
      simplified protocol by collecting dose-response data from six production lots of
      EBT3 film at doses up to 480 cGy. In this work, we used eight different scanners
      of two different models - Epson 10000XL and V700; post-exposure times before
      scanning from 30 minutes to 9 days; ambient temperatures for scanning spanning 23
      degrees F and two film orientations. Scanning was in 48-bit rgb format at 72 dpi
      resolution. Dose evaluation was conducted using a triple-channel dosimetry
      method. To validate the simplified protocol, patient specific IMRT QA was
      performed using a Varian Trilogy Linac to expose EBT3 films. Scanning and film
      analysis was done following the protocol. RESULTS: The results indicated that the
      dose-response data could be fit by a set of related rational functions leading to
      the description of a universal calibration curve. A simplified protocol was
      established where dose-response data for a specific film lot, scanner, and
      scanning conditions could be derived from no more than two films exposed to known
      doses. In most cases only one calibrated exposure was required. Using the Gamma
      test criterion of 2%/2mm to evaluate the measurements, passing rates ranged
      between 95% and 99%. CONCLUSIONS: We have demonstrated a simplified protocol to
      measure doses delivered by an IMRT treatment plan using only the patient film,
      one calibration film, one unexposed film, and applying a single scan to acquire a
      digital image for calculation and analysis. The simplification and time-savings
      provide a practical solution for using radiochromic film for routine IMRT QA
      without sacrificing spatial resolution for convenience. David Lewis, Andre Micke
      and Xiang Yu are all employed by Ashland Specialty Ingredients the manufacturer
      of GAFCHROMIC EBT3 radiochromic film that is the subject of the work presented in
      the Abstract.

PMID- 28517800
TI  - SU-E-T-203: Development of a QA Software Tool for Automatic Verification of Plan
      Data Transfer and Delivery.
AB  - PURPOSE: Consistency verification between the data from treatment planning system
      (TPS), record and verification system (R&V), and delivered recorder with visual
      inspection is time consuming and subject to human error. The purpose of this work
      is to develop a software tool to automatically perform such verifications.
      METHODS: Using Microsoft visual C++, a quality assurance (QA) tool was developed
      to (1) read plan data including gantry/collimator/couch parameters, multi-leaf
      collimator leaf positions, and monitor unit (MU) numbers from a TPS (Xio,
      CMS/Elekta, or RealART, Prowess) via RTP link or DICOM transfer, (2) retrieve
      imported (prior to delivery) and recorded (after delivery) data from a R&V system
      (Mosaiq, Elekta) with open database connectivity, calculate MU independently
      based on the DICOM plan data using a modified Clarkson integration algorithm, and
      (4) compare all the extracted data to identify possible discrepancy between TPS
      and R&V, and R&V and delivery. RESULTS: The tool was tested for 20 patients with
      3DCRT and IMRT plans from regular and the online adaptive radiotherapy
      treatments. It was capable of automatically detecting any inconsistency between
      the beam data from the TPS and the data stored in the R&V system with an
      independent MU check and any significant treatment delivery deviation from the
      plan within a few seconds. With this tool being used prior to and after the
      delivery as an essential QA step, our clinical online adaptive re-planning
      process can be speeded up to save a few minutes by eliminating the tedious visual
      inspection. CONCLUSIONS: A QA software tool has been developed to automatically
      verify the treatment data consistency from delivery back to plan and to identify
      discrepancy in MU calculations between the TPS and the secondary MU check. This
      tool speeds up clinical QA process and eliminating human errors from visual
      inspection, thus improves safety.

PMID- 28517801
TI  - SU-E-T-175: A Study on Design and Fabrication of 25 * 25 cm2 Beam Monitor for
      Scanning Carbon Beam.
AB  - PURPOSE: The KHIMA is developing a superconducting cyclotron of 430 MeV/u for
      carbon therapy. In order to verify the irradiated beam dose and position,
      detectors have been developed. The detector has a considered in the active area
      of 25*25cm2 to cover the entire beam scanning area. To minimize the loss of data
      during beam irradiation, a fast data acquisition system was required. METHODS: A
      PPIC type was adopted. To measure the beam position and profile, the electrode of
      PPIC was designed to have a strip pattern. The PCB technique was applied to large
      area with thin FR-4 plate of electrodes. The chamber has a strip interval of
      1.7mm. He was used as the filling gas in order to reduce the ion collection time.
      Output signal from the detector connected to the two charge integrators was
      transferred every 10us. The signal can be stored temporarily in memory of FPGA
      through one of 2 integrators. RESULTS: The fabricated large electrode plates did
      not show any deformation on their shape. Depending on the beam position, the
      amount of dose from the ion chamber will be measured. For fast data acquisition,
      the DAQ board was fabricated by using 2 charge integrators and the FPGA. The
      obtained data from the ion chamber was displaced on the PC screen every 10us. The
      fluence map of a single layer will be shown on the PC screen at the end of beam
      irradiation on the layer. The output data from the profile monitor will be
      compared with Gafchromic Film results. CONCLUSIONS: PCB method for active area of
      thin electrodes was used in the strip pattern. To reduce the loss of data during
      irradiation, 2 charge integrators are used alternately. The response of the
      readout data was set 1 0us. The beam tests will be performed with the MC-50
      Cyclotron.

PMID- 28517802
TI  - SU-E-T-147: Film Dosimetry Verification for TSE Using An Epson Scanner.
AB  - PURPOSE: To commission and verify an Epson scanner for film dosimetry for total
      skin electron beam therapy (TSEB). METHODS: Use data from an IBA PPC40 parallel
      plate ion chamber and Sun Nuclear QED skin diode detectors as standard; we have
      made comparisons to the film measurement using Kodak XV films. Hurter-Driffield
      (HD) curve are established for 6 MeV total skin electron beams at a source-to
      surface distance (SSD) of 5 m. Also HD curves are built for 6 MeV at a 100 cm
      SSD. Dose profiles for a series of oblique incident large electron fields are
      measured using the film for approximately 80 cGy dose delivered at the peak. The
      film is then scanned using two scanners, an Epson expression 10000 XL and a Vidar
      VXR-16 Dosimetry Pro. The optimal scanning conditions (e.g., dot per pixel size,
      internal color correction scheme) are chosen for the Epson scanner. Matlab is
      then used to analyze the optical density (OD) of the scanned films. A
      transmission densitometer made by Tobias Associates transmission is used to
      analyze the films to give a classical standard. RESULTS: The analysis of the
      Epson scanner is presented in two forms: one with and one without the HD
      correction from the established HD curve. The error analysis gives an uncertainty
      of 5% without the HD correction. An improved result of approximately 3% is found
      when an HD correction is applied to the analysis. CONCLUSIONS: A simple Epson
      scanner satisfies the commissioning standards for TSEB when an HD curve
      correction is applied.

PMID- 28517803
TI  - SU-E-T-187: Clinical Use of the Software for the Automation of Treatment Field
      Parameters Verification Prior to Radiation Delivery.
AB  - PURPOSE: Verification of treatment field parameters by therapists take place
      prior to every or first fraction. Such verification or field timeout should be
      completely independent from record-and-verify system. It is performed manually
      via reading treatment parameters from linac screen and comparing them to
      treatment plan. We evaluate clinical use of software allowing automation of field
      timeout. METHODS: The program for automated timeout performs three tasks.Plan
      information is extracted from PDF printouts generated by Eclipse (Varian Medical
      Systems, Palo Alto, CA) treatment planning system. User selects patient, plan and
      field to be compared with the field moded-up at the linac. Information from the
      Varian (Varian Medical Systems) linac's screen is extracted using video signal
      splitter and VGA2USB converter (Epiphan Systems, Ottawa, CA). Image farther
      undergoes character recognition, which works reliably for 1X, Trilogy and 2100C
      linacs used in out tests.The plan and linac screen information are output to the
      computer screen and user is alerted if mismatch is observed. The software uses
      tolerances established in out clinic. The program also outputs auxiliary
      information, e.g. bolus, which is not well alerted by or can be omitted in the
      record and verify system. In the workflow tested, PDF printouts are uploaded for
      the software during second check and automatic timeout is performed for all
      treatments except v-sim and first fraction (of each treatment plan). RESULTS: The
      software has friendly user interface and is easily included in clinical work
      flow. With the error rate being extremely low, we don't have data yet to claim
      that automated timeout provides higher safety than manual; however, it definitely
      cuts timeout time to 2-3sec per fields versus 10sec, if done manually.
      CONCLUSIONS: Field timeout automation is practicable and fits well into clinical
      workflow. It improves patient throughput and is expected to improve patient
      safety. CONFLICT OF INTEREST: S. Kriminski and I. Lysiuk: provisional patent
      application is submitted to United States Patent and Trademark Office.

PMID- 28517804
TI  - SU-E-T-158: Neutron Damage of Power Electronics Used during Image Guidance in
      Proton Therapy.
AB  - PURPOSE: A series of measurements were performed in a clinical proton therapy
      beam to assess the sensitivity of silicon-based electronics in commercial x-ray
      generators to single event burnout from the secondary neutron background in
      proton therapy treatments. METHODS: Failure rates were nondestructively measured
      in various metal oxide semiconductor field-effect transistors (MOSFETs) as a
      function of applied voltage using a dedicated test circuit board. Neutrons were
      produced by 230 MeV protons stopping in a brass beam target and high beam current
      was used to accelerate testing. Neutron fluences were measured by activation
      analysis of carbon and aluminum in both the test setup and in situ at the
      generator. Failure rates were determined by scaling results based on beam monitor
      output to the relevant neutron fluence rate. RESULTS: Current pulses from the
      test board clearly indicated the onset of single event burnout without destroying
      the MOSFET. The neutron fluence measured on the test board was 4.3 +/- 0.8*106 n
      cm-2 MU-1 and this is consistent with previous measurements. The MOSFET failure
      rate decreased rapidly with a reduction in the applied voltage and is 20-30 times
      lower in higher-rated components at the same voltage. Under nominal operating
      conditions the estimated failure rate is tens of failures per year for a
      generator 6m from the treatment position. CONCLUSION: The sensitivity of x-ray
      generator power electronics to neutron-induced single-event burnout is
      significant and can affect the implementation of image-guided techniques for
      proton therapy. Strategies and system designs to mitigate this phenomenon are
      being investigated to help enable x-ray generators withstand the proton therapy
      environment. This research was supported by the NIH/NCI under grant number 6-PO1
      CA 21239.

PMID- 28517806
TI  - SU-E-T-169: Initial Investigation into the Use of Optically Stimulated
      Luminescent Dosimeters (OSLDs) for In-Vivo Dosimetry of TBI Patients.
AB  - PURPOSE: To report on an initial investigation into the use of optically
      stimulated luminescent dosimeters (OSLDs) for in-vivo dosimetry for total body
      irradiation (TBI) treatments. Specifically, we report on the determination of
      angular dependence, sensitivity correction factors and the dose calibration
      factors. METHODS: The OSLD investigated in our work was InLight/OSL nanoDot
      dosimeters (Landauer Inc.). Nanodots are 5 mm diameter, 0.2 mm thick disk-shaped
      Carbon-doped Al2O3, and were read using a Landauer InLight microstar reader and
      associated software.OSLDs were irradiated under two setup conditions: a) typical
      clinical reference conditions (95cm SSD, 5cm depth in solid water, 10*10 cm field
      size), and b) TBI conditions (520cm SSD, 5cm depth in solid water, 40*40 cm field
      size,). The angular dependence was checked for angles ranging +/-60 degree from
      normal incidence. In order to directly compare the sensitivity correction
      factors, a common dose was delivered to the OSLDs for the two setups. Pre- and
      post-irradiation readings were acquired. OSLDs were optically annealed under
      various techniques (1) by keeping over a film view box, (2) Using multiple scan
      on a flat bed optical scanner and (3) Using natural room light. RESULTS: Under
      reference conditions, the calculated sensitivity correction factors of the OSLDs
      had a SD of 2.2% and a range of 5%. Under TBI conditions, the SD increased to
      3.4% and the range to 6.0%. The variation in sensitivity correction factors
      between individual OSLDs across the two measurement conditions was up to 10.3%.
      Angular dependence of less than 1% is observed. The best bleaching method we
      found is to keep OSLDs for more than 3 hours on a film viewer which will reduce
      normalized response to less than 1%. CONCLUSIONS: In order to obtain the most
      accurate results when using OSLDs for in-vivo dosimetry for TBI treatments,
      sensitivity correction factors and dose calibration factors should all be
      determined under clinical TBI conditions.

PMID- 28517807
TI  - SU-E-T-179: MVCB Pelvic Surface Dosimetry.
AB  - PURPOSE: To compare commonly clinically available methods of estimating skin dose
      for a Megavoltage Conebeam CT of the pelvis. METHODS: The clinical 6 MV conebeam
      uses 15 MU on a Siemens Oncor linac. Film tests using XV-2 film were done on a
      solid water phantom, as were tests using a parallel plate ion chamber at 2 mm
      depth. A Rando pelvic phantom was set up for a MVCB CT, and a cylindrically
      symmetric Isorad 6-12 MV PDM diode was placed at various angles around the
      phantom and irradiated using a 150 MU 6 MV arc beam with the same geometry as the
      clinical conebeam, giving higher and more accurate readings than would be
      obtained with the 15 MU conebeam. A comparison was made with the Pinnacle 8.0m
      treatment planning system. A strip of Optically Stimulated Luminescence
      dosimeters provides an accurate check of the surface dose distribution. RESULTS:
      All methods revealed an expected lateral asymmetry in the dose due to the
      starting and stopping angles of 270 (-90) and 110 for the conebeam. On the sides
      of the phantom, the diode dose was comparable to the Pinnacle-calculated dose at
      a depth of 3-5 mm. Near the anterior portion the diode dose was about 5% higher
      than the maximum Pinnacle-calculated dose at that angle. This difference is
      partly due to the increased diode response at shorter SSDs and higher dose rates,
      and to the geometry with the arc beam radiation being mainly anterior to
      posterior. The skin dose, corresponding to a depth of about 2 mm, is expected to
      be somewhat lower. CONCLUSIONS: To estimate pelvic skin dose in the MV CB
      geometry, corrections for measurement depth and geometry can be used to improve
      the dosimetry for these common clinically available dosimeters.

PMID- 28517805
TI  - SU-E-T-197: A Comprehensive Variance Reporting System and an Analysis of
      Variances Reported at Our Institution.
AB  - PURPOSE: It is essential for radiation oncology departments to have comprehensive
      patient safety and quality programs. Two years ago we undertook a systematic
      review of our safety/QA program. Existing policies were updated and new policies
      created where necessary. One crucial component of any safety/QA program is
      continually updating it based on current information, the 'check' and 'act'
      portions of the Deming Cycle. We accomplished this with a transparent variance
      reporting system and a safety/QA committee reviewing and acting on reported
      variances. METHODS: With 5 radiation oncology centers in our institution, we
      needed to devise a system that would allow anyone to report a variance and
      provide our QA committee the ability to review variances system-wide. We
      developed the system using web-based tools. The system allows individuals to
      report variances, anonymously or named, specify the nature of the variance and
      indicate the tools used to identify the variance. RESULTS: In 2011, 285 variances
      were reported, 102 were reported by physicists, 86 anonymously, 71 by therapists
      and 26 by dosimetrists. We realized the need to develop clear classifications for
      variances. We added a high priority category, defined as variances which resulted
      in or had the potential to result in harm to a patient or when a policy is
      purposely overridden. Of the 285 variances reported, 5 were high priority. We
      created a process variance category, defined as variances where a specific
      clinical process is not followed. Of the 285 reported variances 155 were process
      variances. CONCLUSIONS: Reporting of variances through a centralized database is
      central toward developing a robust patient safety/quality assurance program.
      Anonymous reporting fosters a non-punitive environment, and promotes the 'safety
      culture'. The goal of such a system is to review trends in clinical processes and
      ultimately to improve safety/quality by reducing variances associated with these
      processes.

PMID- 28517808
TI  - SU-E-T-151: Effect of Surface Dose and Depth of Maximum Dose with Physical Wedge
      Filters for 6MV Flattened and 7MV Unflattened Photon Beams.
AB  - PURPOSE: To evaluate impact on surface dose, Depth of dose maximum (dmax) and
      depth dose distribution due to physical wedge filters for different wedge angle
      were studied for 6MV flattened (6MV FB) and 7MV unflattened (7MV UFB) photon
      beams. METHODS: The flattening filter and primary collimator are the major
      sources of producing the scattered radiation and these parameters affect the
      surface dose, dmax and dose distribution. In this study, open fields surface
      dose, dmax and depth dose distribution values were compared with physical wedge
      filter for 6MV FB and 7MV UFB .The measurement carried out in Siemens - ARTISTE
      linear accelerator with diode detector along the central axis of the beam at 100
      cm source to surface distance using IBA blue water phantom for 6MV FB and 7MV UFB
      x-ray beams. RESULTS: The surface dose increased as the field size increased for
      open and physical wedge fields for 6MV FB and 7MV UFB beams. For open fields,
      Surface doses relative to the dose at dmax ranged from 0.443 to 0.569 and 0.463
      to 0.668 for field sizes of 5 * 5 to 20*20 cm2 for the 7MV UFB and 6MV FB beam
      respectively. The measured surface dose for 150, 300,450 and 600 wedge field
      values are 0.396 to 0.504, 0.366 to 0.484, 0.342 to 0.464 and 0.347 to 0.47
      respectively for 7MV UFB and 0.424 to 0.566, 0.398 to 0.555, 0.3860 to 0.5430 and
      0.389 to 0.55 respectively for 6MV FB. CONCLUSIONS: We found that dmax of wedged
      beams were higher than those open beams for field size up to 10 * 10 cm2 ,
      Surface doses of wedged beams were lower than those of open beams for 7MV UFB and
      6MV FB. Surface dose of the 7MV UFB were lower than the 6MV FB for open and
      wedged beams.

PMID- 28517810
TI  - SU-E-T-181: Development of a Single-Marker-Based Optical Tracking System to
      Enhance Patient Safety in Radiotherapy.
AB  - PURPOSE: To develop an accurate and efficient single-marker-based optical
      tracking system to enhance patient safety and quality of care in radiotherapy.
      METHODS: The optical tracking system consists of a Polaris camera as well as in
      house software. The camera is mounted inside the treatment room and detects the
      location of a single infra-red (IR) reflective marker affixed on patient skin in
      real-time. The tracking system safeguards patient from treating wrong sites by
      comparing real-time marker position to the position predicted by virtual
      simulation, which is independent of couch or any indexing system. The deviation
      of marker position is shown in color (red or green) to indicate accuracy of
      patient positioning. The system works in concert with record-and-verify (R&V)
      system to further enhance patient safety and smooth clinic work flow. Marker
      information matching the patient under treatment is automatically loaded by the
      tracking system when a setup or treatment field is loaded in R&V. In non-coplanar
      treatment, the system automatically adjusts expected marker coordinators by
      accounting for each beam's couch angle extracted from R&V. RESULTS: Accuracy of
      the developed tracking system on a pelvis phantom has been verified against a
      CBCT system to be within 1.0 mm for coplanar treatment. In non-coplanar
      treatment, uncertainty of the system increases as the distance of the marker
      relative to treatment isocenter. The system precisely and automatically loads in
      patient and marker information for each beam, in concert with our R&V system.
      CONCLUSIONS: We have developed an accurate and efficient single IR marker-based
      optical tracking system for patient treatment position verification. It
      significantly enhances patient safety with streamlined clinic work flow. The
      system can be readily upgraded for high-precision radiotherapy with the use of
      multiple markers (>4).

PMID- 28517811
TI  - SU-E-T-153: Detector-Grade CVD Diamond for Radiotherapy Dosimetry.
AB  - PURPOSE: To evaluate the use of commercially available detector-grade synthetic
      diamond films made via chemical vapor deposition (CVD) as x- ray detectors for
      radiotherapy dosimetry. METHODS: A detector was fabricated using high-quality
      single crystal CVD diamond films (0.5 * 3 * 3 mm3) with 0.4 mm3 sensitive
      volumes, which were encapsulated with PMMA. The detector was placed in a (30 * 30
      * 30 cm3) PTW water phantom. Six- and ten-MV photons from an Elekta Synergy linac
      were measured using an SSD of 90 cm and typically a 10-cm phantom depth with a 10
      * 10 cm2 field size in the central axis of the beam. Data acquisition was
      performed using a PTW UNIDOS E electrometer with a 100-V bias. The detector was
      evaluated by measuring leakage current, priming dose, response dynamics, dose
      linearity, dependence on dose rate, percent depth dose (6 and 10 MV photons) and
      output factors. Some measurements were compared with a Si diode detector, 0.04
      and/or 0.13-cc ion chamber(s). RESULTS: Leakage currents were negligible (~1 pA)
      given the overall average sensitivity of the material (680 nC/Gy at 100 V).
      Detector current rise and fall times were < 2 s. Dose measurements up to 5 Gy
      were linear. A slight dependence on nominal dose rates up to 500 MU/min was seen
      with Fowler fitting parameter delta = 0.981. Percent depth dose profiles compared
      well to a 0.13-cc ion chamber up to 25 cm depths for 10-MV photons. Output
      factors measured well for field widths 5-15 cm; below 5 cm, differences are seen
      between all four different detectors as expected. CONCLUSIONS: The type of
      diamond tested has potential to be used for small field dosimetry due to its
      small sensitive volume and high sensitivity. Further experiments are ongoing and
      detector packaging is yet to be optimized.

PMID- 28517809
TI  - SU-E-T-190: Design, Development, and Evaluation of a Modified, Anthropomorphic,
      Head, Quality Assurance Phantom for Use in Stereotactic Radiosurgery.
AB  - PURPOSE: To develop and evaluate a modified anthropomorphic head phantom for
      evaluation of stereotactic radiosurgery (SRS) dose planning and delivery.
      METHODS: A phantom was constructed from a water equivalent, plastic, head-shaped
      shell. The original phantom design, with only a spherical target, was modified to
      include a nonspherical target (pituitary) and an adjacent organ at risk (OAR)
      (optic chiasm), within 2 mm, simulating the anatomy encountered when treating
      acromegaly. The target and OAR spatial proximity provided a more realistic
      treatment planning and dose delivery exercise. A separate dosimetry insert
      contained two TLD for absolute dosimetry and radiochromic film, in the sagittal
      and coronal planes, for relative dosimetry. The prescription was 25Gy to 90% of
      the GTV with >= 10% of the OAR volume receiving >= 8Gy. The modified phantom was
      used to test the rigor of the treatment planning process, dosimeter
      reproducibility, and measured dose delivery agreement with calculated doses using
      a Gamma Knife, CyberKnife, and linear accelerator based radiosurgery systems.
      RESULTS: TLD results from multiple irradiations using either a CyberKnife or
      Gamma Knife agreed with the calculated target dose to within 4.7% with a maximum
      coefficient of variation of+/-2.0%. Gamma analysis in the coronal and sagittal
      film planes showed an average passing rate of 99.3% and 99.5% using +/-5%/3mm
      criteria, respectively. A treatment plan for linac delivery was developed meeting
      the prescription guidelines. Dosimeter reproducibility and dose delivery
      agreement for the linac is expected to have results similar to the results
      observed with the CyberKnife and Gamma Knife. CONCLUSIONS: A modified
      anatomically realistic SRS phantom was developed that provided a realistic
      clinical planning and delivery challenge that can be used to credential
      institutions wanting to participate in NCI funded clinical trials. Work supported
      by PHS CA010953, CA081647, CA21661 awarded by NCI. DHHS.

PMID- 28517812
TI  - SU-E-T-192: Computer Vision for Final Online Treatment Parameter Verification.
AB  - PURPOSE: In a typical model of Radiation Oncology data flow, treatment plan is
      designed on treatment planning station (TPS) under the supervision of physician
      and physicist, and machine specific parameters are pushed to Record and Verify
      system (RV) for treatment data storage, where it stays available for daily
      uploads to treatment station. While various QA programs could be established to
      verify uncorrupted planning data storage and transfer, the ultimate goal is a
      daily confirmation of patient treatment parameters versus original treatment
      plan. METHODS: A new computer vision approach, RTcheck, is used to digitize
      loaded machine parameters directly from the screen of Varian Clinical Console
      every time before the beam is turned on by a therapist. The verification engine
      runs a check against the parameters automatically extracted from the printed
      postscript planning report (Pinnacle, Philips) prepared during planning stage and
      approved by physician. All important beam data, MUs, jaws position, beam energy,
      couch angle, and wedge specifiers are displayed side by side on the screen of
      RTcheck station. All field verifications are recorded to a log file, periodically
      reviewed by a physicist. RESULTS: In our clinical tests, the electronic
      verification of machine treatment parameters shortened patient 'on the table'
      time, as the manual therapist's 'time out' check before every beam on may take up
      to several minutes for patient treatments with multiple beams (more than 10). Our
      analysis of verification logs revealed several instances of a small X1 jaw
      position discrepancy of 0.1cm for jaw position range of 0 to -2cm. After jaw
      recalibration, the problem was eliminated. CONCLUSIONS: RTcheck is the end-to-end
      quality assurance approach to verify data flow from TPS to treatment machine for
      every patient treatment. Computer vision approach may help reduce human error
      factor, and shorten patient treatment time. CONFLICT OF INTEREST: S. Kriminski
      and I. Lysiuk: provisional patent application is submitted to United States
      Patent and Trademark Office.

PMID- 28517813
TI  - SU-E-T-164: Clinical Implementation of ASi EPID Panels for QA of IMRT/VMAT Plans.
AB  - PURPOSE: To investigate various issues for clinical implementation of aSi EPID
      panels for IMRT/VMAT QA. METHODS: Six linacs are used in our clinic for EPID
      based plan QA; two Varian Truebeams, two Varian 2100 series, two Elekta Infiniti
      series. Multiple corrections must be accounted for in the calibration of each
      panel for dosimetric use. Varian aSi panels are calibrated with standard dark
      field, flood field, and 40*40 diagonal profile for beam profile correction.
      Additional corrections to account for off-axis and support arm backscatter are
      needed for larger field sizes. Since Elekta iViewGT system does not export gantry
      angle with images, a third-party inclinometer must be physically mounted to back
      of linac gantry and synchronized with data acquisition via iViewGT PC clock. A
      T/2 offset correctly correlates image and gantry angle for arc plans due to iView
      image time stamp at the end of data acquisition for each image. For both Varian
      and Elekta panels, a 5 MU 10*10 calibration field is used to account for the
      nonlinear MU to dose response at higher energies. Acquired EPID images are
      deconvolved via a high pass filter in Fourier space and resultant fluence maps
      are used to reconstruct a 3D dose 'delivered' to patient using DosimetryCheck.
      Results are compared to patient 3D dose computed by TPS using a 3D-gamma
      analysis. RESULTS: 120 IMRT and 100 VMAT cases are reported. Two 3D gamma
      quantities (Gamma(V10) and Gamma(PTV)) are proposed for evaluating QA results.
      The Gamma(PTV) is sensitive to MLC offsets while Gamma(V10) is sensitive to
      gantry rotations. When a 3mm/3% criteria and 90% or higher 3D gamma pass rate is
      used, all IMRT and 90% of VMAT QA pass QA. CONCLUSIONS: After appropriate
      calibration of aSi panels and setup of image acquisition systems, EPID based 3D
      dose reconstruction method is found clinically feasible.

PMID- 28517814
TI  - SU-E-T-202: Comprehensive Quality Assurance Procedures for Uniform Scanning
      Proton Therapy Machines.
AB  - PURPOSE: Quality assurance (QA) is essential in safe and accurate delivery of
      radiation therapy. However, QA in proton therapy is challenging due to
      complicated and often facility-specific beam delivery systems and limited beam
      time for QA. The purpose of this study is to develop an efficient and
      comprehensive QA procedure for a multi-room proton therapy center using uniform
      scanning beams. METHODS: Our proton therapy center is comprised of a 230 MeV
      cyclotron, one fixed beam room, two inclined beam rooms, and one gantry room.
      Uniform scanning is employed exclusively in all treatment rooms. A rfDaily QA3
      (Sun Nuclear Inc., Melbourne, Florida) together with home-made devices is used
      for daily QA. Parallel plane chambers, a multi-layer ionization chamber array
      (Zebra, IBA dosimetry, Schwarzenbruck, German), and an IC profiler (Sun Nuclear
      Inc., Melbourne, Florida) are used to QA the characteristics of the uniform
      scanning beams, including output, range, modulation width, flatness, symmetry,
      and penumbra, for both monthly and annual QA. QA procedures and acceptance
      criteria were developed, taking into account the likelihood and potential risk of
      failure, as well as the available equipment, personnel and other resources.
      RESULTS: QA procedures and tolerances were developed for daily, monthly and
      annual QA at our proton therapy center. Daily QA is performed by radiation
      therapists, and can be completed within 30 minutes for all rooms. Monthly QA and
      annual QA are performed by physicists, taking about 4 hours and a weekend
      respectively. Trend analysis was performed for various machine characteristics,
      such as machine output, range, flatness, and symmetry. CONCLUSION: QA standards
      are desired in Radiation Oncology, but not many standards are developed and
      available for proton therapy. In the mean time, facility-specific QA procedures
      should be developed based on the equipment failure modes and available resources.

PMID- 28517815
TI  - SU-E-T-146: Reference Dosimetry for Protons and Light-Ion Beams Based on Graphite
      Calorimetry.
AB  - PURPOSE: The IAEA TRS-398 code of practice can be applied for the measurement of
      absorbed dose to water under reference conditions with an ionization chamber. For
      protons, the combined relative standard uncertainty on those measurements is less
      than 2% while for light-ion beams, it is considerably larger, i.e. 3.2%, mainly
      due to the higher uncertainty contributions for the water to air stopping power
      ration and the W air-value on the beam quality correction factors kQ,Q0 . To
      decrease this uncertainty, a quantification of kQ,Q0 is proposed using a primary
      standard level graphite calorimeter. This work includes numerical and
      experimental determinations of dose conversion factors to derive dose to water
      from graphite calorimetry. It also reports on the first experimental data
      obtained with the graphite calorimeter in proton, alpha and carbon ion beams.
      METHODS: Firstly, the dose conversion has been calculated with by Geant4 Monte
      Carlo simulations through the determination of the water to graphite stopping
      power ratio and the fluence correction factor. The latter factor was also derived
      by comparison of measured ionization curves in graphite and water. Secondly,
      kQ,Q0 was obtained by comparison of the dose response of ionization chambers with
      that of the calorimeter. RESULTS: Stopping power ratios are found to vary by no
      more than 0.35% up to the Bragg peak, while fluence correction factors are shown
      to increase slightly above unity close to the Bragg peak. The comparison of the
      calorimeter with ionization chambers is currently under analysis. For the
      modulated proton beam, preliminary results on W air confirm the value recommended
      in TRS-398. Data in both the non-modulated proton and light-ion beams indicate
      higher values but further investigation of heat loss corrections is needed.
      CONCLUSIONS: The application of graphite calorimetry to proton, alpha and carbon
      ion beams has been demonstrated successfully. Other experimental campaigns will
      be held in 2012. This work is supported by the BioWin program of the Wallon
      Government.

PMID- 28517817
TI  - SU-E-T-157: Reproducibility of CVD Diamond Detectors for Radiotherapy Dosimetry.
AB  - PURPOSE: Three diamond x-ray detectors fabricated in-house using films from the
      same batch of commercially-available chemical vapor deposition (CVD) diamond were
      investigated for performance inter-comparability under clinically relevant
      conditions. METHODS: Detectors were based on single-crystal CVD diamond films
      (0.5 * 3 * 3 mm3) with 0.4 mm^3 sensitive volumes, which were encapsulated with
      PMMA. Detectors were placed in a (30 * 30 * 30 cm3) PTW water phantom. Six-MV
      photons from an Elekta Synergy linac were measured using an SSD of 90 cm and 10
      cm phantom depth with a 10 * 10 cm2 field size in the central axis of the beam.
      Data acquisition was performed using a PTW UNIDOS E electrometer. Leakage
      current, priming dose, response dynamics, dose linearity, dependence on dose rate
      and angular dependence were used to evaluate differences between diamond
      detectors. RESULTS: Differences were seen in leakage currents before (< 1.5 pA)
      and after (< 12 pA) irradiation. A priming dose of ~7 Gy and rise and fall times
      of 2 s were found for all three detectors. Sensitivities differed by up to 10%.
      Dependence on dose rate was similar (Fowler fitting parameter, delta = 0.92
      0.94). Angular dependence was minimal (97-102% average). Differences in detector
      performance appeared to be primarily due to film thickness, which can
      significantly change sensitivities and applied fields for detectors with small
      sensitive volumes. CONCLUSIONS: Although films were sourced from the same
      manufactured batch, small deviations were seen between detectors such that
      correction factors may be required much like natural diamonds used in existing
      commercial detectors. Differences in sensitivity and dependence on dose rate most
      likely originate from variation in film thickness due to manufactured tolerances.
      Preselecting films by thickness is important to help eliminate variability in
      detector response where small sensitive volumes are used.

PMID- 28517816
TI  - SU-E-T-186: An Automated Quality Assurance Tool for HDR Treatment Planning.
AB  - PURPOSE: Treatment planning for high dose rate (HDR) brachytherapy requires many
      user inputs, all of which are potential sources of error. The goal of quality
      assurance (QA) is to ensure that errors are not made. In this study, we developed
      a software program to analyze the treatment printout from the HDR treatment
      planning computer and flag any suspected errors. METHODS: The treatment printout
      from the HDR planning computer is imported by the software. The software then
      performs the following checks: (1) verifies that the correct source was chosen
      (we have multiple in our database), (2) performs an independent decay of the Ir
      192 source, (3) verifies source step size, (4) verifies the offsets and indexer
      lengths in the catheter definitions based upon expected values for the applicator
      used, (4) performs an independent 2nd check of dose to a cloud of dose points
      surrounding the treatment region, (5) verifies that the dose per fraction and the
      number of fractions were entered correctly in the planning computer, and (6)
      verifies that the dose volume histogram (DVH) metrics were within acceptable
      tolerances. The software then prints this information to a PDF file, which is
      appended to the original treatment printout and placed in the patient's medical
      record. RESULTS: This QA tool has now been implemented for six months in our
      clinic, and is a critical QA tool in our HDR program. Although each plan is
      checked by an independent 2nd physicist, this tool provides an additional
      independent check on the treatment plan. CONCLUSIONS: A simple series of
      automatic 2nd checks helps reduce the risk of errors occurring in the treatment
      planning portion of HDR brachytherapy and can easily be implemented.

PMID- 28517818
TI  - SU-E-T-196: Commissioning for Volumetric Modulated Radiation Therapy on Varian
      Clinac 21EX.
AB  - PURPOSE: Recently the volumetric arc therapy (VMAT) technology such as RapidArc
      is widely distributed in Japan. These technologies are normally provided by the
      high spec linear accelerator such as Trilogy, Novalis Tx, Synergy, et al. The
      specific DICOM-file is generally used for commissioning of these technologies. On
      the other hand, we had to apply RapidArc into historic linear accelerator. This
      title expresses an experience how we performed the commissioning of RapidArc with
      the old linear accelerator. METHODS: Two Varian's linear accelerators "Clinac
      21EX" equipped with Millenium multi-leaf collimator and a Varian's treatment
      planning system "Eclipse ver.8.9" were used for this study. The commissioning for
      RapidArc was performed in energy 4,6,10,15 MV (Max-DR: 250, 600, 400, 600
      MU/min). Commissioning procedure composed two categories: the general machine QA
      for DMLC-IMRT procedure and the specific RapidArc QA procedure. In RapidArc QA
      procedure, we modified DICOM-file to apply into the potential spec of Clinac 21EX
      optimally. The specific MLC-motion sequence and the gantry rotation speed were
      created by the dedicated programs (Shaper and DicomEdit, Varian) for RapidArc QA
      procedure. Each tolerance value was defied by the data from daily/monthly QA and
      the paper by Ling et al. RESULTS: As the results of the general machine QA
      procedure, the variance of radiation output during static/dynamic gantry rotation
      was less than 1%. The deference of fence tests during static/dynamic gantry
      rotation and RapidArc were less than 1 mm in each. However, the results of the
      RapidArc QA were worse than the latest machine (especially variable gantry speed)
      and it was careful to define tolerance level. CONCLUSION: The procedure of
      commissioning for RapidArc on historic linear accelerator was proposed. Several
      minor revisions for DICOM-file should be required for suitable commissioning and
      it may ensure the tolerance limit for gantry/MLC-leaf motion speeds.

PMID- 28517819
TI  - SU-E-T-168: Development of a Liquid Scintillation Detector for External Beam
      Dosimetry.
AB  - PURPOSE: The goal of this research was to design a liquid scintillation dosimeter
      that could be used forrelative dosimetry of linear accelerator fields. The
      project emphasized minimization of cost and ease of use. METHODS: The
      scintillator that was used in this research was BETAMAX- ES scintillation
      cocktail from MPBiomedical. This particular scintillator was selected due to its
      relatively high scintillation yield and lowcost. The entirety of the scintillator
      used the measurements was supplied free of cost. The housing for the liquid was
      constructed from PVC and is cylindrical with one tapered end. One fiber of the
      dual optical fibers transmits the generated photons to the CCD while the other
      fiber is used for Cerenkovsubtraction.The detector used comes from a Philips
      SPC880NC webcam. The plastic casing of the webcamwas removed so that only the
      printed circuit board, USB cable and lens eyepiece holder remained. Thesensor
      employed is the Sony ICX098QB CCD, which is 3.2mm by 2.4mm and each pixel is
      5.6mm by 5.6mm. A small cylindrical insert was manufactured that was inserted
      into the lens eyepiece holder to get adequate mechanical coupling of the fibers
      to the CCD face. Images were acquired with a freeware image acquisition tool,
      SharpCap, and analyzed with theMatlab commercial math package from Mathworks.
      RESULTS: Measurements have been performed that show that the detector is able to
      accurately measuretissue maximum ratio and the relative dose factor. The detector
      was able to accurately measurephysical wedge factors and made good predictions of
      the modulation factor for a patient's 7-field IMRT plan. CONCLUSIONS: This work
      has shown that relative dosimetry can be performed using an inexpensive
      liquidscintillation detector. This could be expanded to include an array of
      liquid scintillator cells formeasurement of beam profiles and other more complex
      problems.

PMID- 28517820
TI  - SU-E-T-178: Optically Stimulated Luminescence (OSL) Dosimetry: A Study of A
      Al2O3:C Assessed by PENELOPE Monte Carlo Simulation.
AB  - PURPOSE: To use the Monte Carlo code PENELOPE to study attenuation and tissue
      equivalence properties of a-Al2O3:C for OSL dosimetry. METHODS: Mass attenuation
      coefficients of alpha-Al2O3 and alpha-Al2O3:C with carbon percent weight
      concentrations from 1% to 150% were simulated with PENELOPE Monte Carlo code and
      compared to mass attenuation coefficients from soft tissue for photon beams
      ranging from 50kV to 10MV. Also, the attenuation of primary photon beams of 6MV
      and 10MV and the generation of secondary electrons by alpha-Al2O3 :C dosimeters
      positioned on the entrance surface of a water phantom were studied. RESULTS: A
      difference of up to 90% was found in the mass attenuation coefficient between the
      pure ?agr;-A12O3 and the material with 150% weight concentration of dopant at 1.5
      keV, corresponding to the K-edge photoelectric absorption of aluminum. However
      for energies above 80 keV the concentration of carbon does not affect the mass
      attenuation coefficient and the material presents tissue equivalence for the
      beams studied. The ratio between the mass attenuation coefficients for ?agr
      A12O3:C and for soft tissue are less than unit due to the higher density of the
      ?agr-A12O3 (2.12 g/cms ) and its tissue equivalence diminishes to lower
      concentrations of carbon and for lower energies due to the relation of the
      radiation interaction effects with atomic number. The larger attenuation of the
      primary photon beams by the dosimeter was 16% at 250 keV and the maximum increase
      in secondary electrons fluence to the entrance surface of the phantom was found
      as 91% at 2MeV. CONCLUSIONS: The use of the OSL dosimeters in radiation therapy
      can be optimized by use of PENELOPE Monte Carlo simulation to provide a study of
      the attenuation and response characteristics of the material.

PMID- 28517821
TI  - SU-E-T-150: The Basic Dosimetric Properties of NIPAM Polymer Gel Dosimeter.
AB  - PURPOSE: To asses a series of basic dosimetric properties such as
      reproducibility, linearity, tissue equivalency, dose rate and energy independency
      for NIPAM polymer gel dosimeter. METHODS: The NIPAM gel was manufactured
      according to the method, described by senden et al (2006). The gels were
      irradiated approximately 2 h after manufacturing and MR images of the gel were
      made 24 h after irradiation. Transverse relaxation rates (R2=T2?1 ) were obtained
      from the signal decay data using the proper data analyzer. In order to
      investigate the absorbed dose response reproducibility, the experiment was
      repeated three times using the same batch of monomer, irradiation method,
      scanning parameters and conditions, also with analyzing two set of the gel with
      different batches of chemical the effect of different batches were investigated .
      For assessing if the NIPAM gel dosimeter response is dependent on different
      photon energies, two sets of NIPAM gel were irradiated using a 9 MV linear
      accelerator and a 60co. The effect of different dose rate on gel response was
      studied in SSD of 80, 90, 100, 110 and 120 and radiation beam were calibrated to
      give 5Gy in each SSD. To investigate the linearity of the gel, the vials were
      irradiated from 1 to 35 Gy. In order to verify tissue equivalency, effective
      atomic number and relative electron density of NIPAM dosimeter were calculated
      using CT number, and compared with tissue. RESULTS: This polymer gel found to be
      tissue equivalent. The results showed that the dose response of NIPAM polymer gel
      is highly reproducible in same and different batches of chemical and its response
      was linear up to 26 Gy. Energy and dose rate had no effect on NIPAM gel response.
      CONCLUSIONS: NIPAM gel dosimeter appears to be a promising dosimeter in all
      aspects of dosimetric properties which were assessed in this study.

PMID- 28517822
TI  - SU-E-T-189: Arc Splitting for VMAT Patient QA.
AB  - PURPOSE: To determine the need for arc splitting for VMAT prostate patient
      quality assurance. METHODS: Prior to Eclipse version 10.0, a verification plan
      for VMAT treatment could only be created which mirrored the clinical plan; if the
      plan called for a full arc, then the verification plan also contained a full arc.
      In this case, for a center that uses the Sun Nuclear MapCheck device with its
      Isocentric Mounting Fixture, the full fluence of an arc is delivered en face to
      the device. The question arose as to whether partial arcs, if they could be
      created, would fail a center's criteria, while the full arc passed them, in
      effect, whether there are cancellations occurring and not being observed. With
      Eclipse version 10.0, it is now possible to split a clinical arc into many
      subdivisions for verification, the software recommends no more than 40 partial
      arcs, for computing speed limitations. Twelve VMAT plans for prostate patients
      were investigated, in order to search for the aforementioned cancellations. Two
      full arcs were used clinically in all cases. Verification plans were created
      consisting of (1) the two full arcs; (2) 8 partial arcs of 90 degrees each; and
      (3) 16 partial arcs of 45 degrees each. These were all analyzed against our
      criteria of 3%/3mm with a threshold of 10%, and 95% of points passing. RESULTS:
      Of 288 partial arcs and 49,670 points analyzed, there were a total of 100 points
      (0.2%) that failed the 3%/3mm criteria. No arcs, however, failed the 95% passing
      criteria. Moreover, there was no evidence of cancellation; if a point failed low,
      there was no corresponding high failure in another partial arc. CONCLUSIONS: In
      this study, splitting a full arc into partial arcs revealed no unseen failures.

PMID- 28517823
TI  - SU-E-T-161: SOBP Beam Analysis Using Light Output of Scintillation Plate Acquired
      by CCD Camera.
AB  - PURPOSE: To analyze Bragg-peak beams in SOBP (spread-out Bragg-peak) beam using
      CCD (charge-coupled device) camera - scintillation screen system. We separated
      each Bragg-peak beam using light output of high sensitivity scintillation
      material acquired by CCD camera and compared with Bragg-peak beams calculated by
      Monte Carlo simulation. METHODS: In this study, CCD camera - scintillation screen
      system was constructed with a high sensitivity scintillation plate (Gd2O2S:Tb)
      and a right-angled prismatic PMMA phantom, and a Marlin F-201B, EEE-1394 CCD
      camera. SOBP beam irradiated by the double scattering mode of a PROTEUS 235
      proton therapy machine in NCC is 8 cm width, 13 g/cm2 range. The gain, dose rate
      and current of this beam is 50, 2 Gy/min and 70 nA, respectively. Also, we
      simulated the light output of scintillation plate for SOBP beam using Geant4
      toolkit. RESULTS: We evaluated the light output of high sensitivity scintillation
      plate according to intergration time (0.1 - 1.0 sec). The images of CCD camera
      during the shortest intergration time (0.1 sec) were acquired automatically and
      randomly, respectively. Bragg-peak beams in SOBP beam were analyzed by the
      acquired images. Then, the SOBP beam used in this study was calculated by Geant4
      toolkit and Bragg-peak beams in SOBP beam were obtained by ROOT program. The SOBP
      beam consists of 13 Bragg-peak beams. The results of experiment were compared
      with that of simulation. CONCLUSIONS: We analyzed Bragg-peak beams in SOBP beam
      using light output of scintillation plate acquired by CCD camera and compared
      with that of Geant4 simulation. We are going to study SOBP beam analysis using
      more effective the image acquisition technique.

PMID- 28517825
TI  - SU-E-T-152: Development of a Phantom for Commissioning and Patient Specific QA
      for Volumetric Modulated Arc Therapy (VMAT).
AB  - PURPOSE: To design a cost effective phantom for commissioning tests and patient
      specific quality assurance in VMAT techniqueMethods: The phantom is made of PMMA
      with the physical density of 1.18 gm/cc. It consists of 20 numbers of 20cm
      diameter discs connected together in a horizontal stack, making a cylinder of
      length 20cm. The centers of the discs are drilled with 2.1cm hole which
      accommodates chamber sleeve of near 2.1cm diameter, which is made of Delrin with
      the physical density of 1.414gm/cc. The cylindrical geometry of the phantom is
      ideal for rotational therapy QA like VMAT or Rapid arc. The entire phantom is
      self supporting and hence no supporting bar or holders are in the path of beam
      geometry. The chamber sleeve itself acts as the supporting rod for these discs
      and it can be inserted in to the disc assembly from distance of-9cm to +10cm from
      the origin and hence any axial point from -9cm to +10cm with respect to isocenter
      can be used for point dose measurement. The other side of the chamber sleeve is
      filled by spacer rod for sustaining the discs in place. The films can be
      inserted, transversely in any XZ plane from -9cm to +10cm from the origin between
      the discs next to the chamber center. RESULTS: Simultaneous irradiation for the
      chamber and the film is done for VMAT plans without collapsing the gantry angles
      to nominal angle of zero. Evaluated the results using RIT film analysis software
      for gamma index of 3%, 3mm. Good agreement is found with more than 95% of pixels
      passing 3% 3mm criteria. The point dose verification showed less than 3%
      variation with TPS planned dose. CONCLUSIONS: Most of the commercial QA systems
      needs gantry to be collapsed to zero degree to perform QA for modern RT
      techniques. Especially for techniques like VMAT, collapsing gantry to zero will
      fail to validate the influence of gantry speed on dose delivery.

PMID- 28517824
TI  - SU-E-T-199: The Radiological Physics Center's Credentialing Dosimetry Reviews:
      Their Effect on Clinical Trial Deviation Rates.
AB  - PURPOSE: To describe the Radiological Physics Center's (RPC) methods to evaluate
      an institution's ability to meet protocol guidelines in order to decrease NCI
      clinical trial deviation rate. METHODS: The RPC's dosimetry group utilizes 3
      methods of assessing an institutions ability to meet the protocol treatment
      specifications. These methods involve a clinical and dosimetric review of a
      treatment plan submitted by the institution prior to the first patient being
      treated on a protocol. The three evaluation methods include use of site/treatment
      modality specific benchmark cases, evaluation of a previous patient treated in a
      similar fashion and a rapid review of the first patient placed on a trial prior
      to start of treatment. The dosimetric review consists of an independent dose
      recalculation using RPC measured data or RPC standard dosimetry data. The
      clinical review assesses the patient's DVHs and contouring of the tumor volume
      and critical structures, typically in conjunction with a radiation oncologist.
      RESULTS: Over the past 5 years the RPC has performed these QA reviews for several
      of the clinical trial groups for several different disease sites and treatment
      modalities. We have reviewed 1366 treatment plans as a part of credentialing (97
      gynecological, 223 prostate, 1046 breast) where 222 failed the first submission
      requiring the RPC to interact with the submitting institution to resolve the
      discrepancy. The review of the benchmarks has resulted in 18% of the institutions
      requiring intervention by the RPC. Performing these reviews has identified
      potential clinical and dosimetric problem areas that could possibly have resulted
      in 17% of the charts reviewed to receive a minor or major deviation. CONCLUSIONS:
      The RPC's clinical and dosimetry review of submitted treatment plans before or
      early in the treatment process has helped to reduce the deviation rates on
      protocols. Work supported by PHS grant CA 10953 awarded by NCI, DHHS.

PMID- 28517826
TI  - SU-E-T-191: PITSTOP: Process Improvement Techniques, Software Tools, and
      Operating Principles for a Quality Initiative Discovery Framework.
AB  - PURPOSE: To develop a quality initiative discovery framework using process
      improvement techniques, software tools and operating principles. METHODS: Process
      deviations are entered into a radiotherapy incident reporting database.
      Supervisors use an in-house Event Analysis System (EASy) to discuss incidents
      with staff. Major incidents are analyzed with an in-house Fault Tree Analysis
      (FTA). A meta-Analysis is performed using association, text mining, key word
      clustering, and differential frequency analysis. A key operating principle
      encourages the creation of forcing functions via rapid application development.
      RESULTS: 504 events have been logged this past year. The results for the key word
      analysis indicate that the root cause for the top ranked key words was
      miscommunication. This was also the root cause found from association analysis,
      where 24% of the time that an event involved a physician it also involved a
      nurse. Differential frequency analysis revealed that sharp peaks at week 27 were
      followed by 3 major incidents, two of which were dose related. The peak was
      largely due to the front desk which caused distractions in other areas. The
      analysis led to many PI projects but there is still a major systematic issue with
      the use of forms. The solution we identified is to implement Smart Forms to
      perform error checking and interlocking. Our first initiative replaced our daily
      QA checklist with a form that uses custom validation routines, preventing
      therapists from proceeding with treatments until out of tolerance conditions are
      corrected. CONCLUSIONS: PITSTOP has increased the number of quality initiatives
      in our department, and we have discovered or confirmed common underlying causes
      of a variety of seemingly unrelated errors. It has motivated the replacement of
      all forms with smart forms.

PMID- 28517827
TI  - SU-E-T-163: Thin-Film Organic Photocell (OPV) Properties in MV and KV Beams for
      Dosimetry Applications.
AB  - PURPOSE: To characterize dosimetric properties of low-cost thin film organic
      based photovoltaic (OPV) cells to kV and MV x-ray beams for their usage as large
      area dosimeter for QA and patient safety monitoring device. METHODS: A series of
      thin film OPV cells of various areas and thicknesses were irradiated with MV
      beams to evaluate the stability and reproducibility of their response, linearity
      and sensitivity to absorbed dose. The OPV response to x-rays of various linac
      energies were also characterized. Furthermore the practical (clinical)
      sensitivity of the cells was determined using IMRT sweeping gap test generated
      with various gap sizes. To evaluate their potential usage in the development of
      low cost kV imaging device, the OPV cells were irradiated with kV beam (60-120
      kVp) from a fluoroscopy unit. Photocell response to the absorbed dose was
      characterized as a function of the organic thin film thickness and size, beam
      energy and exposure for kV beams as well. In addition, photocell response was
      determined with and without thin plastic scintillator. RESULTS: Response of the
      OPV cells to the absorbed dose from kV and MV beams are stable and reproducible.
      The photocell response was linearly proportional to the size and about slightly
      decreasing with the thickness of the organic thin film, which agrees with the
      general performance of the photocells in visible light. The photocell response
      increases as a linear function of absorbed dose and x-ray energy. The sweeping
      gap tests performed showed that OPV cells have sufficient practical sensitivity
      to measured MV x-ray delivery with gap size as small as 1 mm. CONCLUSIONS: With
      proper calibration, the OPV cells could be used for online radiation dose
      measurement for quality assurance and patient safety purposes. Their response to
      kV beam show promising potential in development of low cost kV radiation
      detection devices.

PMID- 28517828
TI  - SU-E-T-201: Safety-Focused Customization of Treatment Plan Documentation.
AB  - PURPOSE: Plan report documentation contains numerous details about the treatment
      plan, but critical information for patient safety is often presented without
      special emphasis. This can make it difficult to detect errors from treatment
      planning and data transfer during the initial chart review. The objective of this
      work is to improve safety measures in radiation therapy practice by customizing
      the treatment plan report to emphasize safety-critical information. METHODS:
      Commands within the template file from a commercial planning system (Eclipse,
      Varian Medical Systems) that automatically generates the treatment plan report
      were reviewed and modified. Safety-critical plan parameters were identified from
      published risks known to be inherent in the treatment planning process. Risks
      having medium to high potential impact on patient safety included incorrect
      patient identifiers, erroneous use of the treatment prescription, and incorrect
      transfer of beam parameters or consideration of accessories. Specific examples of
      critical information in the treatment plan report that can be overlooked during a
      chart review included prescribed dose per fraction and number of fractions, wedge
      and open field monitor units, presence of beam accessories, and table shifts for
      patient setup. RESULTS: Critical information was streamlined and concentrated.
      Patient and plan identification, dose prescription details, and patient
      positioning couch shift instructions were placed on the first page. Plan
      information to verify the correct data transfer to the record and verify system
      was re-organized in an easy to review tabular format and placed in the second
      page of the customized printout. Placeholders were introduced to indicate both
      the presence and absence of beam modifiers. Font sizes and spacing were adjusted
      for clarity, and departmental standards and terminology were introduced to
      streamline data communication among staff members. CONCLUSIONS: Plan reporting
      documentation has been customized to concentrate and emphasize safety-critical
      information, which should allow for a more efficient, robust chart review
      process.

PMID- 28517829
TI  - SU-E-T-174: Synopsis of the Experimental and Monte Carlo Calculated Values of the
      Radial EPOM Shift of Cylindrical Ionization Chambers for Photon-Beam Dosimetry.
AB  - PURPOSE: According to the concept of the effective point of measurement (EPOM),
      the values of depth z serving as the variable of photon-beam depth dose
      distributions in water measured with cylindrical ionization chambers are commonly
      corrected according to the formula zeff=zR+?z, were zeff is the depth of the
      EPOM, zR the depth of the reference point of the chamber, i.e. of its symmetry
      axis, and Az the EPOM shift. Agreed-upon values of the EPOM shift are for
      instance ?z=-0.6r (IAEA TRS 398, 2000) and ?z=-0.5r (DIN6800-2,2008) with
      r=radius of the air-filled volume. The EPOM concept holds in the falling as well
      as in the rising curve branch. The Az versus r relationship is currently
      reviewed. METHODS: Measurements of the EPOM shift of cylindrical ionization
      chambers for 6/15 MV photons had been based upon a comparison with depth
      dependent dose distributions in water measured with the Roos chamber (PTW
      Freiburg). Its EPOM position (1.5 mm below the front face) had been determined by
      comparison with radiochrome films. (Looe et al, Phys.Med.Biol. 2011;56:4267
      4290). Available are also the experimental EPOM shift values by Huang et al,
      Physica Medica 2010;26:126-131 and the classical value of Johansson et al, IAEA 
      SM-222/35,243-270(1978). Accurate Monte Carlo values had been supplied by Tessier
      and Kawrakow, Med.Phys. 2010;37:96-107. RESULTS: As shown by the graphical
      display of Az versus r, the relationship is nonlinear, shaped as a hockey stick,
      with values around -0.2 mm for the "pinpoint" chambers and with values near -1.4
      mm for the often-used chambers with radii near 3 mm. For r ranging from 1 to 4
      mm, the relationship can be approximated by ?z = -(2.25 mm)*[1-exp(-0.0122 r4)]
      with r in mm. CONCLUSIONS: Time has come for a nonlinear updating of the EPOM
      shift versus radius relationship of cylindrical ionization chambers applied in
      photon-beam dosimetry.

PMID- 28517830
TI  - SU-E-T-145: MRI Gel Dosimetry Applied to Dose Profile Determination for 50kV X
      Ray Tube.
AB  - PURPOSE: The aim of this study was to use MRI gel dosimetry to determine the dose
      profile of 50kV MAGNUM(r) X-ray tube, MOXTEK Inc., in order to calibrate small
      solid dosimeters of alanine, tooth enamel and LiF-TLDs, commonly used in clinical
      quality assurance and datation dosimetry. METHODS: MAGIC-f polymer gel was kept
      in two plastic containers of 100mL, avoiding attenuation of the primary beam
      trough the wall. Beam aberture of 3mm and dose rate of 16.5Gy/min were set,
      reproducing irradiation conditions of interest. The dose rate was assumed based
      on data of the vendor information of the tube and dose of 30Gy was delivered at
      the surface of the gel. MAGIC-f gel was irradiated at source-surface
      distances(SSD) of 0.1cm and 1.0cm. After 24hours of irradiation, gel was scanned
      in an Achieva(r) 3T Philips(r) MRI tomography using relaxometry sequence with 32
      Echos, Time-to-Echo(TE) of 15.0ms, Time-to-Repetition(TR) of 6000ms and Field-of
      View(FOV) of 0.5*0.5*2.0mm. Dose map at the central plain of irradiation was
      calculated from T2 relaxometry map. RESULTS: The gel dosimetry results evidenced
      a build-up depth of 0.13cm for SSD=0.1cm and no build-up was detected for
      SSD=1.0cm. However, the dose profile evidenced high gradient of dose in SSD=0.1,
      decreasing the dose from 100% to 30% in 1.4cm depth inside the gel; In turn, the
      dose distribution is homogeneous after 0.4cm deth for SSD=1.0cm. CONCLUSIONS: MRI
      gel dosimetry using MAGIC-f presented as feasible technique to determine dose
      profiles for kilovoltage x-rays tubes. The results evidenced that the calibration
      of small solid dosimeters can be performed using SSD of 1.0cm in the 50kV
      MAGNUM(r) X-ray tube using 0.4cm/g/cm3 filter. This work was funded supported by
      CNPQ, CAPES and FAPESP.

PMID- 28517831
TI  - SU-E-T-184: LINAC Commissioning Measurements Utilizing the Cylindrical Arc Check
      Phantom.
AB  - PURPOSE: New devices for IMRT and VMAT QA are continually becoming available.
      Despite the availability of these devices they are underutilized for routine
      mechanical QA. In this work we take advantage of the cylindrical geometry of the
      Arc Check phantom to perform tests that are an integral part of commissioning and
      routine QA. METHODS: The Arc Check is a cylindrical phantom with a diameter of
      26.59cm and a 1386 diode array arranged on a cylindrical plane. Owing to its
      cylindrical design it is capable of measuring entry and exit radiation. For this
      experiment the Arc Check was set up using the mechanical pointer at 86.7cm SSD.
      The device was leveled using its inclinometer and was properly rotated to align
      with the lasers and cross-hair. With the phantom set up at the expected isocenter
      of the LINAC, 100MUs with a 10*10 field were delivered at different gantry
      angles, couch and collimator rotations. Each delivery was recorded individually
      and for each one the radiation center at the entry and exit levels of the
      detector were estimated. That provided the path of the radiation center through
      the device. The radiation path was reconstructed for each rotation individually
      and the coincidence of the mechanical and radiation isocenter was evaluated.
      RESULTS: A procedure and MATLAB routine were developed that accepted as input the
      text files that are the output of the Arc Check measurement and geometrically
      reconstructed in 3-dimensions the isocenter and radiation central axis for each
      rotation. The coincidence of the radiation and mechanical isocenter was verified.
      CONCLUSIONS: This work demonstrates that by utilizing the geometry of a
      commercially available device multiple mechanical LINAC tests that are part of
      routine QA can be evaluated in one single setup.

PMID- 28517832
TI  - SU-E-T-156: Robust Algorithms for Correction of Predicted Electronic Portal
      Imager Response.
AB  - PURPOSE: Predicted electronic portal imaging device (EPID) response, as
      calculated by a commercial treatment planning system (TPS), is up to 15% lower
      than measured EPID response for off-axis IMRT fields. Two original algorithms are
      presented to correct for EPID prediction errors. The EPID prediction algorithm
      and a recent image-to-dose conversion algorithm are each tested for ability to
      identify TPS dose calculation errors. METHODS: By comparing test images to
      respective predictions, correction factors were calculated to modify the EPID
      diagonal calibration profile (applied via radial symmetry). Secondly,
      image/prediction comparisons were used to compute a 2D correction matrix for EPID
      predictions, to account for radially-asymmetric errors. Over 50 IMRT fields of
      varying complexity were tested with each correction technique, and with a diode
      array. Absolute dose and beam-profile errors were separately induced into the TPS
      and a number of IMRT plans were recalculated and measured with three systems - an
      EPID prediction system, an EPID image-to-dose conversion system, and a diode
      array - for comparison to verification plans. RESULTS: With the profile
      correction, TPS predictions agree much better with EPID measurements, yielding
      improvement in gamma pass rates (3%,3mm) of over 30% on average for off-axis IMRT
      fields. Since off-axis prediction errors are not radially-symmetric, the matrix
      correction further improves pass rates by 5% on average (up to 30%) for fields
      where the profile correction is limited. The EPID prediction system was unable to
      catch either induced TPS error, while both the image-to-dose conversion system
      and the diode array indicated both errors. CONCLUSIONS: Profile correction is
      effective and efficient though approximate, due to radial symmetry. The matrix
      correction is comprehensive but requires computational manipulation of DICOM
      images. Users must be aware that EPID prediction systems may be unable to catch
      delivered IMRT inaccuracies due to calculation errors downstream from the actual
      fluence calculation.

PMID- 28517833
TI  - SU-E-T-195: Experience in Implementing Intraoperative Radiation Therapy for
      Accelerated Partial Breast Irradiation Using Low-Energy X-Ray Source.
AB  - PURPOSE: To present our preliminary experience and quality-assurance (QA)
      procedures in implementing intraoperative-radiation therapy (IORT) for
      accelerated-partial-breast irradiation (APBI) using the Axxent-system controller
      (Xoft Inc.) Methods: IORT was implemented in our institution utilizing a 50-keV x
      ray source. APBI allows breast conserving in patients with early-stage-breast
      cancer by delivering radiation to the lumpectomy bed via an applicator balloon
      filled with water, to which a prescribed dose of 20 Gy was applied to its
      surface. In-situ anesthesiology, breast-surgery and radiation-oncology teams were
      required to achieve this procedure. Calibration of the source, including
      temperature and pressure corrections, was performed by the controller resulting
      in a calibration factor, which was manually introduced by a physicist into an in
      house program providing the corrected dwell times. Evaluation of exposure
      measurements determined that personnel standing behind glass-rolling shields
      during irradiation were sufficient protection. RESULTS: We have successfully
      treated four patients to date. Surgical times averaged about two hours, QA and
      setup of controller took about 30 minutes, while radiation-treatment times ranged
      7.8-10.4 minutes. Exposure to personnel showed a negligible dose compared to
      background based on the in-vivo measurements. Our measurements have shown that
      placement of a shielding layer (FlexiShield) on top of the drape-protected breast
      reduced radiation exposure to in-room personnel. In one case, treatment was
      automatically stopped by the controller due to a sudden undetected cooling water
      flow; due to the pre-treatment training, treatment was successfully resumed
      within a minute after manual adjustment of the flow sensor. CONCLUSIONS:
      Implementation of IORT to treat patients with APBI using low-energy x-ray source
      should follow the manufacturer's recommendations regarding to the acceptance and
      personnel training. Our experience indicates that two physicists are necessary at
      least at the implementation stage. Appropriate training to deal with potential
      problems is crucial before clinical treatment can be ready.

PMID- 28517835
TI  - SU-E-T-177: Deconvolution of Line Dose Profiles with Ionization Chambers -
      Experiences with the First Software Implementation in Mephisto 3.0.
AB  - PURPOSE: To evaluate the first implementation of a deconvolution algorithm in a
      commercial water phantom scanning software. METHODS: Line dose profile
      measurements in a water phantom are an essential part of a quality assurance
      system and in base data measurements in radiotherapy. Usually these measurements
      are performed with waterproof ionization chambers of various sizes. These dose
      profile measurements are broadened by the Gaussian response functions of the
      detectors. In recent studies we showed that the undisturbed line dose profiles
      can be reconstruced by iterative deconvolution of the measured signal profiles
      with the Gaussian detector response functions. Recently, the proposed method was
      implemented in Mephisto 3.0. In this work we analyze the applicability and the
      limits of the deconvolution algorithm for several chambers by comparing the
      result with diode measurements. RESULTS: As long as the dose gradient becomes not
      too steep the deconvolution algorithm is able to reconstruct the undisturbed dose
      profiles with sufficient accuracy. Deviations occur for smallest field sizes in
      which the width of the detector's lateral response functions reaches the
      dimensions of the field. A simple chart for those limits is derived. CONCLUSION:
      The implemented deconvolution algorithm allows a fast and simple correction of
      measured dose profiles broadened by the volume effect of the ionization chambers.
      It offers therefore for the first time a clinical deconvolution of the profiles
      on a regular base and by this the implementation of undisturbed base data in the
      treatment planning systems as well as in the quality assurance process in modern
      radiotherapy.

PMID- 28517834
TI  - SU-E-T-167: Comprehensive Evaluation of EPID Image Acquisition for Integrating
      and Temporal Dosimetry of Fixed-Gantry IMRT and ArcIMRT.
AB  - PURPOSE: To evaluate EPID for dosimetry applications of arc and static-gantry
      IMRT with sliding window (SW) and/or step-and-shoot (SS) deliveries Methods: IMRT
      beams (SW & SS) were designed that generate beam hold-offs and dose rate
      modulation due to MLC motion under 10 * 10 cm jaw. An arcIMRT beam was designed
      by adding gantry movement to the SW field. A 10 cm * 10 cm open beam was also
      used. Despite differences in delivered dose rates/pulse characteristics, the four
      beams should deliver the same total dose. For each beam, various MUs with 6 MV
      beam at 300MU/min were irradiated on EPID which operated in image acquisition of
      integration mode (IM), continuous scanning mode with synchronization (CMs) and
      without (CMn) to beam pulses. Acquired images were evaluated in repeatability,
      dose linearity, and reproducibility (reproduce open beam output in IM). RESULTS:
      In IM, repeatability, dose linearity, and reproducibility were within 1% for all
      dose levels and beams. In CMs, they were within 1-2% if dose rate was maintained
      steady (1) for SW beam (needed a minimum 1.3 MU/cm MLC motion) and (2) arcIMRT
      beam (needed a minimum 1 MU/degree and 2.8 MU/cm MLC motion) and (3) if a minimum
      of 38-40 MU per shoot was used for SS beam. Nonlinearity was observed for fewer
      MUs. This is due to the response of EPID to pulse-length reduction for fixed
      gantry therapy and pulse dropping for arc therapy. The latter produces in-planar
      non-uniformity making EPID unsuitable for temporal dosimetry of arcIMRT.
      Sacrifice in temporal resolution then became necessary such as multi-frames per
      image (eg. ~1 sec/image). In CMn the results were similar to those of CMs.
      However, they showed artifacts, thus this mode was not preferred. CONCLUSIONS: We
      found conditions under which integrating and temporal EPID dosimetry can be used
      for IMRT and arcIMRT dose deliveries.

PMID- 28517836
TI  - SU-E-T-149: Scatter Factors Comparison of 6MV Flattened and 7MV Unflattened
      Beams.
AB  - PURPOSE: To compare the Collimator scatter factor (Sc), Phantom scatter factor
      (Sp) and Total scatter factors (Sc,p) of 6MV flattened Beam (6MV FB) and 7MV
      Unflattened beams (7MV UFB). METHODS: The flattening filter and primary
      collimator are the major sources of producing the scattered radiation. In this
      study, the field sizes from 5*5 cm2 to 40 * 40 cm2 compared for 6MV FB and 7MV
      UFB. We measured Sc,p with CC 13 chamber at the depth of 10 g/cm2 using IBA blue
      phantom and Sc measured with CC 13 chamber at the depth of 10 g /cm2 using
      columnar phantom (TG 74) for 6MV FB and 7MV UFB x-ray beams from a Siemens -
      ARTISTE linear accelerator. The Sp values derived from the Sc,p and Sc Values.
      RESULTS: All the values of Sc,p, Sc and Sp are normalized to 10 * 10 cm2 field
      size the measured values of Sc,p for 6MV FB and 7MV UFB varies from 0.9437 to
      1.0651 and 0.9690 to 1.0283 respectively. The Sc values for 6MV FB and 7MV UFB
      varies from 0.9676 to 1.0212 and 0.9882 to 1.0075 respectively. The Sp values for
      6MV FB and 7MV UFB varies from 0.9752 to 1.0429 and 0.9806 to 1.0206
      respectively. Our study results shows that Sc, Sp & Sc,p for 7MV UFB for smaller
      fields up to 10 * 10 cm2 were higher than 6MV FB and for larger fields greater
      than 10 *10 cm2 it is vice versa. CONCLUSIONS: A scatter factors are measured and
      compared for 6MV FB and 7MV UFB. A significant variation observed for Sc, Sp and
      Sc,p values of 6MV FB and 7MV UFB .This is may be due to flattening filter and
      beam quality.

PMID- 28517838
TI  - SU-E-T-160: Response of EBT2 Gafchromic Film to Possible Stresses Associated with
      in Vivo Measures.
AB  - PURPOSE: to assess the response of EBT2 Gafchromic filmast; to stresses that
      might be imposed on the film when used as an in-vivo dosimeter. The following
      stress factors were investigated: bending the film; compression; and the shearing
      that occurs when cutting the film. METHODS: For bending stress, the film was
      rolled into cylinders of various radii, submerged in water, and exposed to X
      rays. For compression, 64 cm2 pieces of the film were sandwiched within a stack
      of solid water and weights were placed on top of the solid water in order to
      compress the film while being exposed to X-rays. For artifacts that arise from
      cutting the film, pieces of the film were cut either with scissors or a paper
      cutter. The cut film was then exposed uniformly and shearing artifacts introduced
      from cutting the film were identified. The effects of 'light piping' from the cut
      edges of the film were also investigated. A felt tip pen was used to darken the
      cut edges in order to mitigate light piping. The film was scanned with an Epson
      10000 XL scanner in transmission mode and images in the red spectrum were
      analyzed. RESULTS: At 200 cGy exposures, a compression corresponding to 0.6
      kg/cm2 'weight pressure' had less than a 2% influence on the film's response.
      Bending the film had a larger influence, >5%, when the radius of curvature was 1
      cm. Also, larger artifacts were identified when the film was cut with scissors
      and the cut edges were not darkened with a pen. CONCLUSIONS: EBT2 film can
      readily be used as an in-vivo dosimeter within the compression and dose ranges
      investigated. The user should avoid cutting the film with scissors, and also
      avoid excessively bending the film. No COI.

PMID- 28517837
TI  - SU-E-T-188: Evaluation of a 3D Patient Relevant Dose QA Tool: Multiple
      Institutional Studies.
AB  - PURPOSE: To evaluate 3DVHTM as a patient dose-verification and analysis tool
      through multiple institutional studies. Virtual patient doses were measured and
      compared among different vendors' treatment planning systems (TPS) and delivered
      by different vendors' LINACS so that we better understand the uncertainty of
      entire process within a patient undergone radiotherapy. METHODS: One head-and
      neck (H&N) and one lung patient were selected in this study. The DICOM images/RT
      structures along with clinical protocols including prescription doses (59.4Gy for
      H&N and 70.2Gy for lung) and normal&hyphen;tissues tolerances were distributed to
      six institutions. Based on the same criteria, each institution generated their
      IMRT plans for the patients. Four different TPS and six different LINACS were
      used. The conventional per&hyphen;beam IMRT QA using MapCHECK was performed by
      all participants. All the measured and calculated data were sent back to one
      institution for 3DVH analysis. Through the use of planned-dose-perturbation
      (PDP)TM algorithm (Sun Nuclear Corp.), the 'actual-DVHs' were generated and then
      compared to the 'reference-DVHs' from plans. Their differences represented errors
      induced from the combination of TPS dose-calculation algorithm and beam-delivery
      systems. RESULTS: All plans in the study have met the clinical criteria. The 3D
      matching rates for 3%global/3mm (DD/DTA) ranged from 95.8-99.9% for H&N and 93.5
      100% for lung. The dose-difference-histogram for PTV had a mean of 0.67% [0-2%]
      for H&N cases and 1% [0.6-2.8%] for lung cases. The QA tool was able to spot the
      doses outside 3%/3mm criteria for critical structures much easier than
      conventional planar QA methods. In addition, the hot/cold spots at the boundaries
      of collimators are attributed to the uncertainty of collimator-positioning
      greater than 1-mm. CONCLUSIONS: The analysis of IMRT plans in this study has
      shown that 3DVH is a vital QA tool for assessing clinically relevant doses as
      well as diagnosing potential systematic errors from both TPS and delivery
      systems.

PMID- 28517839
TI  - SU-E-T-171: Missing Dose in Integrated EPID Images.
AB  - PURPOSE: A dosimetric artifact has been observed with Varian EPIDs in the
      presence of beam interrupts. This work determines the root cause and significance
      of this artifact. METHODS: Integrated mode EPID images were acquired both with
      and without a manual beam interrupt for rectangular, sliding gap IMRT fields.
      Simultaneously, the individual frames were captured on a separate computer using
      a frame-grabber system. Synchronization of the individual frames with the
      integrated images allowed the determination of precisely how the EPID behaved
      during regular operation as well as when a beam interrupt was triggered. The
      ability of the EPID to reliably monitor a treatment in the presence of beam
      interrupts was tested by comparing the difference between the interrupt and non
      interrupt images. RESULTS: The interrupted images acquired in integrated
      acquisition mode displayed unanticipated behaviour in the region of the image
      where the leaves were located when the beam interrupt was triggered. Differences
      greater than 5% were observed as a result of the interrupt in some cases, with
      the discrepancies occurring in a non-uniform manner across the imager. The
      differences measured were not repeatable from one measurement to another.
      Examination of the individual frames showed that the EPID was consistently losing
      a small amount of dose at the termination of every exposure. Inclusion of one
      additional frame in every image rectified the unexpected behaviour, reducing the
      differences to 1% or less. CONCLUSIONS: Although integrated EPID images nominally
      capture the entire dose delivered during an exposure, a small amount of dose is
      consistently being lost at the end of every exposure. The amount of missing dose
      is random, depending on the exact beam termination time within a frame. Inclusion
      of an extra frame at the end of each exposure effectively rectifies the problem,
      making the EPID more suitable for clinical dosimetry applications. The authors
      received support from Varian Medical Systems in the form of software and
      equipment loans as well as technical support.

PMID- 28517840
TI  - SU-E-T-162: Rapid Assessment of Cyberknife IRIS Variable Collimator Performance
      Using a Commercial Diode Array.
AB  - PURPOSE: To describe an efficient method for verifying the size and centering of
      the radiation field from the Cyberknife IRIS variable collimator with sub
      millimeter accuracy using a general purpose commercially available diode array.
      METHODS: We present a technique using a conventional diode array (Sun Nuclear
      Profiler) with the array at an extended distance of 320 cm. The projection of the
      4 mm diode spacing back to the 80 cm field definition distance gives an effective
      spacing of 1 mm, sufficient to confirm proper operation of the IRIS. We describe
      the data acquisition process and present data comparing the Profiler measurements
      to scanned measurements for both profile and FWHM analysis and reproducibility of
      the technique over repeated measurements. RESULTS: Average difference between
      original water scanner measurements and diode array measurements over the 12
      aperture sizes) from 5 mm to 60 mm) were - 0.14 mm (range 0.03 mm to 0.83 mm).
      Reproducibility and centering measurements had a similar range of accuracy.
      CONCLUSIONS: A general purpose commercially available diode array can be used to
      quickly and accurately characterize the field size and centering of the
      Cyberknife IRIS variable collimator system with sub-millimeter accuracy
      subsequent to service, software recalibration, software upgrades or associated
      with routine QA. This technique avoids the time consuming and cumbersome water
      tank scanning with a diode and the difficulties associated with image based
      measurements (CR or radiochromic film) that require time consuming and careful
      calibration and choice of threshold values.

PMID- 28517841
TI  - SU-E-T-200: IMRT Patient Specific QA for On-Line Adaptive Radiotherapy.
AB  - PURPOSE: On-line adaptive IMRT requires a highly efficient radiotherapy team and
      an intensive amount of work, as well as significant amount of Quality Assurance
      (QA). With regard to patient specific QA, it is clinically unrealistic to perform
      fluence measurements via a QA phantom while patient is setup awaiting treatment.
      We therefore developed an alternative way to check point dose and the IMRT
      fluence right before beam delivery. METHODS: In this study, 28 IMRT plans were
      generated with Prowess Panther 5.1 for three prostate cancer patients on 28 CT
      datasets with CTV and critical organs contoured by treating physicians. The
      corresponding QA plans were generated by Prowess, and then transfered to Pinnacle
      9.2 for fluence recalculation on a flat surface phantom, In addition 28 QA plans
      were delivered on a Siemens Artiste accelerator and fluence were measured with
      Matrixx IMRT Device. We analyzed both point dose and fluence for these 28
      samples. RESULTS: Of all 28 IMRT plans, the point dose difference between Prowess
      and Pinnacle are well within 1%. The point dose difference between measurements
      and Prowess calculation are all within 3%. The passing rates using gamma criteria
      (3%3mm) for the fluence comparison between Prowess and Pinnacle calculation are
      at least 98.5% while the passing rates of the gamma analysis between fluence
      measurement and Prowess calculation are all better than 98.5%. The passing rate
      of gamma difference between Prowess vs Pinnacle and Prowess vs QA measurement is
      less than 1.5% for all 28 samples. Therefore, second TPS (e.g. Pinnacle) can be
      used to verify planned fluencies and can serve as a valuable patient specific QA
      when conventional IMRT QA measurement is not feasible. CONCLUSIONS: A new IMRT
      plan is desired if significant anatomy change from the date of original CT scan
      is observed before the radiation delivery. It is not clinically feasible to check
      the fluence on the machine before radiation delivery while the patient is in the
      treatment suite awaiting radiation delivery. Our method showed here is an
      alternative way to verify the planned fluence with a second TPS and can serve as
      a valuable IMRT patient specific QA in online adaptive radiotherapy.

PMID- 28517842
TI  - SU-E-T-173: TomoTherapy Treatment Couch Velocity Verification Using TomoDose.
AB  - PURPOSE: Accurate TomoTherapy treatment is dependent on multiple parameters,
      including the accuracy of couch velocity during beam delivery and gantry
      rotation. The recent TG-148 protocol recommends quarterly film tests to verify
      the constancy of couch velocity. We determined the feasibility of using TomoDose,
      a quality assurance device, to detect the variation in couch velocity from
      baseline by a deviation of one or two percent. METHODS: The TomoDose unit was
      rotated 90 degrees clockwise so that the long axis, consisting of 107 detectors,
      would translate across the TomoTherapy 'Y' jaws. The collimator field size used
      was the 1 cm mode and the table velocity was set to 0.5 mm/sec to establish a
      baseline. The velocity was then varied by 1% or 2% from nominal. The five tested
      velocities were 0.495, 0.490, 0.500, 0.505 and 0.510 mm/sec. The total
      translation time was kept at a constant 400 sec. The field was progressively
      painted during the scans and was shortened if table velocity was decreased, and
      lengthened as velocity was increased. RESULTS: The baseline field size was 20.03
      cm (400 sec * 0.05 cm/sec). A 2% increase in velocity translated to an increase
      in the field size to 20.39 cm and a 2% decrease in velocity resulted in a
      decrease in field size to 19.64 cm. Similarly, a 1% increase in velocity
      increased the field to 20.18 cm, and a 1% decrease velocity decreased the field
      to 19.76 cm. CONCLUSIONS: An increase or decrease in the couch velocity, for a
      fixed beam delivery time, resulted in an altered radiation field size. The field
      size results are approximately as expected for both the baseline scans as well as
      the modified velocity scans. This study demonstrates that, under these
      conditions, TomoDose can be used to determine small variations in table velocity
      as small as 1 %.

PMID- 28517843
TI  - SU-E-T-183: Managing and Assessing Patients Receiving Radiotherapy with
      Implantable Cardiac Devices.
AB  - PURPOSE: To assess the effectiveness of the management of patients with cardiac
      electronic implantable devices (CEIDS) receiving radiotherapy. METHOD AND
      MATERIALS: In 2005, a formal communication process was established between
      Radiation Oncology and Cardiac Electrophysiology (EP) for the management of
      patients with permanent, implantable cardiac devices receiving radiotherapy. The
      process requires a pre-treatment consult with EP. This information is provided to
      a medical physicist, who works with the primary radiation oncologist and
      dosimetrist. Based on the estimated dose to the device, EP and Radiation Oncology
      will determine the appropriate oversight required for treatment. To assess the
      effectiveness of this program, a retrospective analysis of patients with
      implantable cardiac devices receiving radiotherapy between the years 2005 and
      2011 was performed. RESULTS: Sixty-nine patients with CEIDs (19 implantable
      cardioverter defibrillators (ICDs) and 50 pacemakers) were treated in Radiation
      Oncology between 2005 and 2011. Patients were treated to a variety of sites,
      including 21 patients treated to multiple sites. Doses were estimated prior to
      radiotherapy, and in vivo measurements were obtained for patients near or
      exceeding our institutional device tolerance (ICDs = 1 Gy and ICPs = 2 Gy), or if
      the device was less than 10 cm from the edge of a treatment field. Of the
      patients evaluated, there were only two patients with ICD devices which had a
      partial reset of diagnostic data during their treatment. There were no major
      device failures of arrhythmia detection or treatment. CONCLUSIONS: Our multi
      disciplinary team has worked together to develop a process to manage the care of
      patients with permanent implantable cardiac devices. There have been few device
      events noted in our patient cohort. The team will continue to follow our
      institutional management methodology to assess the appropriate amount of EP care
      necessary during radiation therapy. Laura Horwood is on the speakers bureau for
      Medtronic. Frank Pelosi is on the advisory board for Boston Scientific Corp and
      St. Jude Medical, is receiving an educational grants from Medtronic, St Jude,
      Boston Scientific, Biotronik, and a research grants from Medtronic.

PMID- 28517844
TI  - SU-E-T-155: Dose Response Curve of EBT2 and EBT3 Radiochromic Films to a
      Synchrotron-Produced Monochromatic X-Ray Beam.
AB  - PURPOSE: This work investigates the dose-response curves of Gafchromic EBT2 and
      EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams.
      These dosimeters are being utilized for dose verification in photoactivated Auger
      electron therapy at the LSU Center for Advanced Microstructures and Devices
      (CAMD) synchrotron facility. METHODS: Monochromatic beams of 25, 30 and 35 keV
      were generated on the tomography beamline at CAMD. Ion chamber depth-dose
      measurements were used to calculate the dose delivered to films irradiated
      simultaneously at depths from 0.7 - 8.5 cm in a 10*10*10-cms
      polymethylmethacrylate phantom. AAPM TG-61 protocol was applied to convert
      measured ionization into dose. Calibrations of films at 4 MV were obtained for
      comparison using a Clinac 21 EX radiotherapy accelerator at Mary Bird Perkins
      Cancer Center. Films were digitized using an Epson 1680 Professional flatbed
      scanner and analyzed using the optical density (OD) derived from the red channel.
      RESULTS: For EBT2 film the average sensitivity (OD/dose) at 50, 100, and 200 cGy
      relative to that for 4-MV x- rays was 1.07, 1.20, and 1.23 for 25, 30, and 35
      keV, respectively. For EBT3 film the average sensitivity was within 3 % of unity
      for all three monochromatic beams. CONCLUSIONS: EBT2 film sensitivity shows
      strong energy dependence over an energy range of 25 keV - 4 MV. EBT3 film shows
      weak energy dependence, indicating that it would be the better dosimeter for
      Auger electron therapy. This research was supported by contract W81XWH-10-1-0005
      awarded by The U.S. Army Research Acquisition Activity, 820 Chandler Street, Fort
      Detrick, MD 21702-5014. This report does not necessarily reflect the position or
      policy of the Government, and no official endorsement should be inferred.

PMID- 28517845
TI  - SU-E-T-194: Evaluation and Simulation of Shallow Depth Skin Dose from Couch Top
      in Radiotherapy.
AB  - PURPOSE: When the treatment couch-top contacts the patient, the skin dose to the
      patient also generates clinical significance as the radiation beam passes through
      the couch. In this study, the effect on entrance shallow depth dose was
      investigated for the carbon fiber exact couch-top from Varian Medical System.
      METHODS: An Accredited Dosimetry Calibration Laboratory (ADCL) calibrated PTW
      parallel-plate thin-window chamber was used to measure the doses in the build-up
      region. Firstly, the shallow depth doses at different field sizes, depths and
      incident angle beams were measured for 6MV and 18MV photon beams. To test the
      couch top contribution to the dose distribution, the depth of measurement went
      down to 10cm. The couch was simulated in the Eclipse treatment planning system
      and the related point dose was calculated with different depths. The CT number of
      the couch top was adjusted to generate agreement between measurement and
      simulation. RESULTS: At a 2mm depth, the surface dose increased with the decrease
      of the field size. Comparing with and without the couch top, as field sizes vary
      from 20cm*20cm to 2cm*2cm, the dose increased from 35% to 53% of for 6MV, and
      from 50% to 113% for 18MV. At 0mm depth, the dose difference was most significant
      and is at the level of 300%. Angle incident beam dose increase due to couch top
      varied with complicated dose distribution. Extended Depth Dose measurement shows
      that couch top effect on dose in build-up region extends to depths of 1cm for 6MV
      and 2cm for 18MV. An appropriate CT number setting of the couch top is between 
      200HU to -300HU. CONCLUSIONS: The couch simulation in Eclipse displays better
      dosimetric accuracy in couch contacted skin dose. However, calculation factors
      such as surface definition, heterogeneity, calculation resolution and algorithm
      also need extra consideration.

PMID- 28517846
TI  - SU-E-T-166: Use of an in Vivo Dosimeter to Assess the Implications of Daily
      Prostate Rotations.
AB  - PURPOSE: It is well established that using image guidance for prostate motion
      allows reduction of margin, dose escalation, decreased toxicity and recently
      improved outcomes. However, current methods only account for translational
      motion, not rotational variations. The purpose of this study is to assess whether
      rotations in anatomy lead to significant changes in the delivered dose for
      prostate patients. METHODS: Under an IRB approved protocol, 11 consecutive
      patients underwent prostate IMRT using IGRT with implanted metal-oxide
      semiconductor field-effect transistors (MOSFETs); the Dose Verification System
      (DVS) manufactured by Sicel Technologies. Two dosimeters were implanted per
      patient. From conebeam CT (CBCT) registration, corrections were applied to all
      translational errors. For rotations larger than 3 degrees, patient were
      repositioned and realigned to attempt to correct the rotation. Both translational
      and rotational errors based on the CBCT were documented. The daily DVS readings
      were compared to CBCT rotations about each axis (pitch, roll and yaw) and the
      root-mean square (RMS) rotation. RESULTS: 372 CBCT images were acquired. The
      correlation between rotation and DVS measurement was analyzed using linear
      regression. The R2 value for pitch was 0.059 and 0.144 for each dosimeter,
      respectively. For roll, the R2 values were 0.049 and 0.001. For yaw, the values
      were <0.001. For the RMS rotation, R2 was 0.034 and 0.038. As it could confound
      results, the angular dependence of the dosimeters was measured during
      commissioning and found that it was approximately 0.5% for 5 degree rotations.
      CONCLUSIONS: We did not find any significant correlation between prostate
      rotation around any axis and discrepancy in DVS reading. These results show that
      rotations seen clinically do not have a substantial effect on the dose delivered
      to the prostate. Further studies will attempt to determine at what angle
      rotations begin to affect the dose distribution, if at all.

PMID- 28517847
TI  - SU-E-T-204: A Prototype of Dose-Guided Radiation Therapy.
AB  - PURPOSE: With the advancement in dosimetric devices and the development of dose
      reconstruction algorithm, the implementation of dose-guided radiation therapy
      (DGRT) is feasible. In order for DGRT to be performed clinically, a prototype of
      DGRT was developed in this study. METHODS: The prototype adopted a strategy for
      DGRT that adjusted the treatment plan for future fractions to compensate for
      dosimetric errors from past fractions, which included four main functional
      modules: management of patient plan information, dose reconstruction, dose
      evaluation, plan adjustment. we developed our dose reconstruction procedure,
      including the dosimetric calibration of the portal image acquired using
      electronic portal image device (EPID) during treatment and three-dimensional (3D)
      patient dose reconstruction based on Monte Carlo Finite-size pencil beam (MCFSPB)
      model and Conjugate-gradient (CG) algorithm developed by FDS Team
      (www.fds.org.cn). The dose evaluation tools including 3D Gamma analysis and dose
      volume-histogram (DVH) analysis were also available which were used to compare
      the reconstruction dose with the planning dose. Finally we re-optimizing the
      treatment plan according to the information provided by dose evaluation. RESULTS:
      In order to validate the availability of the workstation prototype, lots of
      experiments were carried out based on head phantom. The result showed that
      disagreement between the reconstructed dose and the planning dose (calculated by
      the Accurate Radiotherapy System (ARTS) developed by FDS Team) was observed by
      the DGRT prototype when there existed position error for head phantom or the
      accelerator delivery was not accurate. CONCLUSIONS: An effective prototype for
      DGRT has been developed. With these techniques, the clinical implementation of
      DGRT is possible in the near future. Supported by the National Natural Science
      Foundation under grant No.30900386 and the National Science Foundation of Anhui
      Province (Nos.090413095 and 111040606Q55).

PMID- 28517848
TI  - SU-E-T-176: Improved Collimator Scattering Factor (Sc) Measurements for Small
      Fields Using Build-Up Caps in Robotic Radiosurgery.
AB  - PURPOSE: The Monte Carlo calculation algorithm in the MultiPlan (Accuray, Palo
      Alto, CA) treatment planning system used for CyberKnife (Accuray) robotic
      radiosurgery requires in-air measurements. In this study, results were compared
      for the impact of build-up caps using a diode detector for small field in-air
      measurements. METHODS: Two acrylic caps custom-made for the SFD diode detector
      (IBA, Germany) of two thicknesses were compared against free-in-air measurements.
      The 1.5 and 5 cm thicknesses correspond to Dmax and a depth beyond the range of
      electron contamination, respectively. A Blue Phantom (IBA) was used to position
      the diode 80 cm SAD. Measurements were made for all 12 fixed cones ranging from 5
      to 60 mm. RESULTS: For the 5 mm cone, there is a 15.6% and 20.0% difference in
      the Sc factor between the 1.5 cm and 5 cm buildup caps, respectively, versus the
      free-in-air measurement. For the 7.5 mm cone, the difference is 6.3% and 10.4%
      for the 1.5 cm and 5 cm buildup caps, respectively, versus the free-in-air
      measurement. While generally decreasing, the Sc factor for either buildup cap
      does not agree within 2% to free-in-air measurements until the cone used is
      larger than 40 mm. Overall, the two buildup caps yield similar Sc factors and the
      differences observed are attributed to electron contamination. CONCLUSIONS: The
      Monte Carlo calculation algorithm used by the CyberKnife planning manual does not
      refer to any build-up caps. This study has shown that, particularly for small
      fields, there are large differences in Sc factors measured with and without
      buildup caps. In general, for fields smaller than 10 mm, build-up caps should be
      carefully chosen, especially in commissioning data.

PMID- 28517849
TI  - SU-E-T-148: An Optimizing Study of a New Multi Channel Virginal Cylinder
      Applicator in Brachytherapy.
AB  - PURPOSE: A new CT/MRI vaginal multichannel applicator was introduced by
      Elekta/Nucletron(r) recently. The multi-lumen cylindrical device intends to
      improve and optimize treatment of local advanced vaginal cancer. The design of
      this applicator includes several inner peripheral channels in equal spacing
      isotropically 5 mm from the surface of cylinder. The central tube provides the
      unique function as it was in traditional single channel treatment. METHODS:
      Ninteen CT image sets of six patients were taken with multichannel applicator
      inserted. The single channel plan was planned before multichannel plan to justify
      the dose coverage to the prescribed volume and the doses received by bladder and
      rectum. The Oncentra(r) Brachytherapy planning system was employed to generate
      forward plan in single channel and inverse plan in multichannel where doses to
      bladder and rectum were evaluated and weighted by using Inverse Planning
      Simulated Annealing (IPSA) algorithm. RESULTS: Figure.1 shows plan Result from
      single channel and Figure.2 shows multichannel Result with IPSA. The comparison
      confirms multichannel provides better coverage of V90, V95 and V100 to the
      prescribed 5 mm vaginal cuff rind. The maximal doses delivered to bladder and
      rectum were reduced and the mean dose was lowered in average by 5-9% and 7-11%
      respectively. CONCLUSIONS: The nature of Brachytherapy is to take advantages of
      short fall off of radiation dose outside the intended treated tumor and minimize
      dose to surrounding tissues and critical organs. However treatment technique and
      plan optimization could be improved and be enhanced to benefit cancer treatment
      from advanced design of the applicators. This study demonstrates a new
      multichannel applicator affords promising conformal treatment to the tumor and
      liberates the doses to the critical structures by using optimization to meet our
      objectives.

PMID- 28517850
TI  - SU-E-T-159: Sensitivity of in Line Real Time Scintillating Fiber Detectors for
      External Beam Treatment Verification and Patient Safety.
AB  - PURPOSE: We studied the sensitivity of a novel transmission fiber scintillator
      array designed and built for in line treatment verification. The purpose of this
      project is to assess the capability of the fiber detector array technology to
      detect treatment errors in real time without false positives to enhance patient
      safety. METHODS: We developed a linear scintillator array detector using
      radiation hard scintillating fibers and high speed parallel signal conditioning
      and data acquisition to monitor external beam treatment fluence in real time. The
      detector captures and resolves the time and amplitude of each linac pulse at each
      MLC segment. The detector has 60 fibers aligned to each MLC leaf and two output
      channels per fiber. The data is captured by a high speed parallel digitizer to
      determine the IMRT beam output delivered to a patient in real time. We evaluated
      the detector peak pulse linearity according to dose rate, MLC positioning, and
      beam energy. We analyzed the detector sensitivity, signal to noise ratio, and
      pulse distribution statistics to determine beam output and fluence in real time.
      RESULTS: We analyzed the response of the detector to 6 MV and 10 MV photon beams.
      The statistical analysis of the detected linac pulses indicates that a minimum of
      20 pulses are required to evaluate MLC positioning and fluence with 3 mm and 3%
      resolution, respectively. During testing, no false positives were detected.
      Linearity with respect to output rate, MLC or jaw opening, and fluence is within
      2%. CONCLUSIONS: Measured sensitivity and signal to noise ratio of a real time
      linear fiber array detector show that delivered beam fluence can be monitored
      every 55 msec, with no observed false positives during treatment to provide in
      vivo real time patient safety and beam monitoring.

PMID- 28517851
TI  - SU-E-T-198: Patient Scheduling Monitor (PSM)-A New Tool for Radiation Therapy
      Patient Scheduling and Workflow Management in an Increasingly Digital
      Environment.
AB  - PURPOSE: To develop an easy-to-use and customizable Patient Scheduling Monitor
      for 1) active monitoring of radiation therapy workflow from CT simulation to the
      start of treatment and 2) for optimizing the workflow based on treatment
      complexity. METHODS: Microsoft Access database and Visual Basic language were
      used to create an in-house software application, Patient Scheduling Monitor
      (PSM). The PSM was designed with three functional modules: a patient schedule
      calculator, a workflow progress tracker, and a workflow evaluator. The PSM
      divides the radiation treatment workflow into 6 tasks including image
      acquisition/fusion, target delineation, dosimetry planning, MD review, physics QA
      and RTT QA. On the day of CT simulation, the scheduling calculator generates a
      planned timeline for each task based on the CT-simulation date and the default
      standard established for each given task and treatment type. Each task within the
      PSM can also be individualized as needed. After simulation, the progress tracker
      enables staff to actively monitor the workflow. The workflow evaluator will query
      the database and analyze the planned versus actual timeline and provide data for
      future workflow analysis. RESULTS: We have used the PSM since Nov, 2011 for 186
      patients. The PSM has allowed us to provide patient start times at the completion
      of simulation. It has helped to improve patient satisfaction. The workflow
      progress tracker enabled us to actively manage the workflow. Currently, for
      patients managed using the PSM, no rescheduling has been required. The use of PSM
      has reduced the average CT simulation to treatment start times. It also has
      improved intradepartmental communications. CONCLUSIONS: An easy-to-use patient
      scheduling monitor has been developed. The PSM has been shown to be an efficient
      and effective tool in managing, assessing and improving the radiation therapy
      workflow and will be useful in managing the timelines in an increasingly dynamic
      working environment.

PMID- 28517911
TI  - Is there a potential of misuse for Magnolia officinalis compounds/metabolites?
AB  - OBJECTIVE: Magnolia bark contains magnolol, metabolized to tetrahydromagnolol and
      honokiol, with both GABA-ergic/cannabimimetic activities, hence of possible
      attraction to vulnerable individuals/recreational misusers. METHODS: A literature
      review, assessment of related anecdotal online Magnolia misuse's reports and an
      overview of Magnolia products' online acquisition possibilities has been here
      described. RESULTS: No peer-reviewed papers about Magnolia
      abuse/misuse/dependence/addiction were identified. Conversely, from a range of
      websites emerged potentially 3 groups of Magnolia misusers: (a) subjects with a
      psychiatric history already treated with benzodiazepines, being attracted to
      Magnolia bark as a "natural sedative"; (b) polydrug misusers, ingesting Magnolia
      with a range of other herbs/plants, attracted by the GABA-ergic/cannabimimetic
      activities; (c) subjects naive to the misusing drugs' scenario, perceiving
      Magnolia as a natural dietary supplement/weight-control compound. CONCLUSIONS: To
      the best of our knowledge, this is the first paper commenting on the possible
      Magnolia derivatives' potential of misuse. Magnolia's recent increase in
      popularity, mainly as a sedative, may be arguably due to its peculiar
      pharmacological properties/acceptable affordability levels/virtually worldwide
      favorable legal status and customers' attraction to a product being perceived as
      "natural" and hence somehow "safe." Future/potent/synthetic magnolol and honokiol
      structural analogues could however contribute to increasing the number of
      synthetic GABA-ergic/cannabimimetic misusing compounds.

PMID- 28517912
TI  - Keeping good friends close - The surface and secreted proteomes of a probiotic
      bacterium provide candidate proteins for intestinal attachment and communication
      with the host.
AB  - Bacteria use cell surface proteins and secreted proteins to interact with host
      tissues. Several dozen previously published proteomics studies have identified
      cell surface proteins for pathogens. In this issue, Celebioglu and Svensson
      (Proteomics 2017, 17, 1700019) use 2D gel electrophoresis and mass spectrometry
      to identify secreted and cell surface proteins of a commensual gut bacterium,
      Lactobacillus acidophilus NCFM. Some of the proteins are known to have functions
      in the cytoplasm, and their presence on the cell surface suggests they might be
      moonlighting proteins. In addition, comparisons of proteins used by pathogenic
      and probiotic species to interact with their hosts could lead to improved
      treatments of infections and chronic diseases that are associated with an
      imbalance of pathogenic and probiotic gut bacteria.

PMID- 28517913
TI  - Sodium-glucose co-transporter-2 inhibitors and diabetic ketoacidosis: An updated
      review of the literature.
AB  - Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are increasingly used for the
      treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1
      diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2is
      may cause diabetic ketoacidosis (DKA). We report details on 2 new cases of SGLT2i
      associated DKA and review the literature for similar cases within randomized
      controlled trials (RCTs), cohort studies and single reports. We searched the
      medical literature for reports of SGLT2i-associated DKA cases. A quantitative
      analysis of frequency and clinical characteristics is reported. The 2 narrative
      cases illustrate that SGLT2i-associated DKA can occur in patients with T1D
      incorrectly diagnosed as T2D, perhaps without the presence of obvious DKA
      precipitating factors. The incidence of SGLT2i-associated DKA was less than
      1/1000 in randomized controlled trials and 1.6/1000 person-years in cohort
      studies. We retrieved detailed data on 105 SGLT2i-associated DKA case reports,
      wherein 35% showed glucose levels of less than 200 mg/dL and 22% were not
      associated with typical triggers. In case reports and in pharmacovigilance
      databases, duration of SGLT2i treatment before DKA onset was extremely variable.
      Fatal SGLT2i-associated DKA episodes were found only in pharmacovigilance
      databases and represented 1.6% of all reported cases. DKA is a rare adverse event
      during SGLT2i therapy. Predisposing and precipitating factors are still
      incompletely understood, although a minority of cases lacked typical DKA
      triggers. More narrative case series and cohort studies are needed to better
      understand the true risk and the spectrum of this adverse event.

PMID- 28517914
TI  - Osimertinib in EGFR T790M-Positive Lung Cancer.

PMID- 28517915
TI  - Microbial Glycosylation of Flavonoids.
AB  - Flavonoids constitute a large group of polyphenolic compounds naturally found in
      plants, which have a wide range of biological activity. Although flavonoids are
      beneficial to human health, their application is limited by their low
      bioavailability and poor water-solubility. Therefore, recently there has been a
      particular interest in glycosylated forms of flavonoids, which usually are better
      soluble, more stable, and more functional compared to their aglycones. Microbial
      transformation of natural flavonoids may be an attractive way of receiving their
      glycosylated derivatives in amounts sufficient for the research on the effect of
      glycoside group on compound properties and for further application of these
      compounds as ingredients of dietary supplements and pharmaceuticals.

PMID- 28517916
TI  - Relationship between ureB Sequence Diversity, Urease Activity and Genotypic
      Variations of Different Helicobacter pylori Strains in Patients with Gastric
      Disorders.
AB  - Association of the severity of Helicobacter pylori induced diseases with
      virulence entity of the colonized strains was proven in some studies. Urease has
      been demonstrated as a potent virulence factor for H. pylori. The main aim of
      this study was investigation of the relationships of ureB sequence diversity,
      urease activity and virulence genotypes of different H. pylori strains with
      histopathological changes of gastric tissue in infected patients suffering from
      different gastric disorders. Analysis of the virulence genotypes in the isolated
      strains indicated significant associations between the presence of severe active
      gastritis and cagA+ (P = 0.039) or cagA/iceA1 genotypes (P = 0.026), and
      intestinal metaplasia and vacA m1 (P = 0.008) or vacA s1/m2 (P = 0.001)
      genotypes. Our results showed a 2.4-fold increased risk of peptic ulcer (95% CI:
      0.483-11.93), compared with gastritis, in the infected patients who had dupA
      positive strains; however this association was not statistically significant. The
      results of urease activity showed a significant mean difference between the
      isolated strains from patients with PUD and NUD (P = 0.034). This activity was
      relatively higher among patients with intestinal metaplasia. Also a significant
      association was found between the lack of cagA and increased urease activity
      among the isolated strains (P = 0.036). While the greatest sequence variation of
      ureB was detected in a strain from a patient with intestinal metaplasia, the sole
      determined amino acid change in UreB sequence (Ala201Thr, 30%), showed no
      influence on urease activity. In conclusion, the supposed role of H. pylori
      urease to form peptic ulcer and advancing of intestinal metaplasia was postulated
      in this study. Higher urease activity in the colonizing H. pylori strains that
      present specific virulence factors was indicated as a risk factor for promotion
      of histopathological changes of gastric tissue that advance gastric malignancy.

PMID- 28517917
TI  - Interaction of Gram-Positive and Gram-Negative Bacteriawith Ceramic Nanomaterials
      Obtained by Combustion Synthesis - Adsorptionand Cytotoxicity Studies.
AB  - This paper presents the interactions of Gram-positive (Staphylococcus aureus) and
      Gram-negative (Pseudomonas putida) bacteria with ceramic materials obtained by
      combustion synthesis. These studies were conducted based on an analysis of the
      adsorption of bacteria onto aggregates of ceramic materials in an aqueous
      suspension. The materials used in the studies were of a nanostructured nature and
      consisted mainly of carbides: silicon carbide (SiC) in the form of nanofibers
      (NFs) and nanorods (NRs), titanium carbide, and graphite, which can also be
      formed by combustion synthesis. Micrometric SiC was used as a reference material.
      Gram-positive bacteria adsorbed more strongly to these materials. It seems that
      both the point of zero charge value and the texture of the ceramic material
      affected the bacterial adsorption process. Additionally, the viability of
      bacteria adsorbed onto aggregates of the materials decreased. Generally, P.
      putida cells were more sensitive to the nanomaterials than S. aureus cells. The
      maximum loss of viability was noted in the case of bacteria adsorbed onto NRSiC
      and NFSiC aggregates.

PMID- 28517918
TI  - Biocontrol of Gray Mold Decay in Pear by Bacillus amyloliquefaciens Strain BA3and
      its Effect on Postharvest Quality Parameters.
AB  - The economic losses caused by postharvest fruits diseases have attracted global
      attention. Traditional chemical fungicide could not meet the need of humans. In
      recent years, microbial agent which has begun to take the place of chemical
      fungicide comes into people's vision. The aim of this paper was to investigate
      the potential of Bacillus amyloliquefaciens strain BA3 for its biocontrol
      capability on gray mold decay of pears and its effect on postharvest quality of
      pears. Compared with other treatments, the inhibition effect on gray mold of
      washed cell suspension of B. amyloliquefaciens was the best. Consequently it was
      utilized in subsequent experiments. Spore germination and germ tube length of
      Botrytis cinerea was 18.72% and 12.85 MUm treated with BA3, while the control
      group was 62.88% and 30.44 MUm. We confirmed that increase of the concentration
      of B. amyloliquefaciens, improved the efficacy of BA3 in controlling gray mold
      decay of pears. Colonization variation of BA3 in wounds of pears was recorded. To
      begin with, the populations of B. amyloliquefaciens increased rapidly and
      remained stable. On the fourth day, there was a declining trend , after that the
      population increased to 4 * 10(5) CFU/wound and remained stable. BA3 had no
      significant effect on mass loss, titratable acidity, firmness and total soluble
      solids of pears that were stored at 25 degrees C for 7 days comparing with
      control group. However, the effect of B. amyloliquefaciens on ascorbic acid was
      significantly higher than that of the control group. Our study indicates that B.
      amyloliquefaciens has a potential as postharvest biocontrol agent on pears.

PMID- 28517919
TI  - Enzymes Involved in Naproxen Degradation by Planococcus sp. S5.
AB  - Naproxen is a one of the most popular non-steroidal anti-inflammatory drugs
      (NSAIDs) entering the environment as a result of high consumption. For this
      reason, there is an emerging need to recognize mechanisms of its degradation and
      enzymes engaged in this process. Planococcus sp. S5 is a gram positive strain
      able to degrade naproxen in monosubstrate culture (27%). However, naproxen is not
      a sufficient growth substrate for this strain. In the presence of benzoate, 4
      hydroxybenzoic acid, 3,4-dihydroxybenzoic acid or vanillic acid as growth
      substrates, the degradation of 21.5%, 71.71%, 14.75% and 8.16% of naproxen was
      observed respectively. It was shown that the activity of monooxygenase,
      hydroxyquinol 1,2-dioxygenase, protocatechuate 3,4-dioxygenase and
      protocatechuate 4,5-dioxyegnase in strain S5 was induced after growth of the
      strain with naproxen and 4-hydroxybenzoate. Moreover, in the presence of naproxen
      activity of gentisate 1,2-dioxygenase, enzyme engaged in 4-hydroxybenzoate
      metabolism, was completely inhibited. The obtained results suggest that
      monooxygenase and hydroxyquinol 1,2-dioxygenase are the main enzymes in naproxen
      degradation by Planococcus sp. S5.

PMID- 28517920
TI  - Characterization of Bacteria Isolation of Bacteria from Pinyon
      Rhizosphere,Producing Biosurfactants from Agro-Industrial Waste.
AB  - Two hundred and fifty bacterial strains were isolated from pinyon rhizosphere and
      screened for biosurfactants production. Among them, six bacterial strains were
      selected for their potential to produce biosurfactants using two low cost wastes,
      crude glycerol and lactoserum, as raw material. Both wastes were useful for
      producing biosurfactants because of their high content in fat and carbohydrates.
      The six strains were identified by 16S rDNA with an identity percentage higher
      than 95%, three strains belonged to Enterobacter sp., Pseudomonas aeruginosa,
      Bacillus pumilus and Rhizobium sp. All strains assayed were able to grow and
      showed halos around the colonies as evidence of biosurfactants production on
      Cetyl Trimethyl Ammonium Bromide agar with crude glycerol and lactoserum as
      substrate. In a mineral salt liquid medium enriched with both wastes, the
      biosurfactants were produced and collected from free cell medium after 72 h
      incubation. The biosurfactants produced reduced the surface tension from 69 to 30
      mN/m with an emulsification index of diesel at approximately 60%. The results
      suggest that biosurfactants produced by rhizosphere bacteria from pinyon have
      promising environmental applications.

PMID- 28517921
TI  - Levels of Organic Compounds, Number of Microorganismsand Cadmium Accumulation in
      Festuca ovina Hydroponic Culture.
AB  - Understanding the microbiological, biochemical and physiological aspects of
      phytoremediation of soil and water environments polluted to different degrees
      with heavy metals has very important theoretical and practical implications. In
      this study, a comparison was made between total cadmium concentration in root and
      shoot tissues as well as concentrations of particular fractions of Cd immobilized
      by roots of Festuca ovina (Sheep's fescue) hydroponically cultivated in nutrient
      solutions supplemented with 1 MUg Cd ml(-1) and those cultivated at 10 MUg Cd ml(
      1). After three weeks of F. ovina cultivation, the number of bacterial CFU and
      the amounts of organic chelators, siderophores, proteins and reducing sugars in
      the growth medium and on the root surface were higher at 10 than at 1 MUg Cd ml(
      1). The grass also reacted to the high Cd concentration by a decrease in plant
      growth and dehydrogenase activity in root tissues. The concentration of Cd
      determined in fractions bound with different strength in roots was significantly
      dependent on Cd concentration in the growth medium. When the plants were grown at
      1 MUg Cd ml(-1), 9% of the immobilized cadmium was loosely bound to the root
      surface, 20% was exchangeable adsorbed, and 28% was bound by chelation; at 10 MUg
      Cd ml(-1), the respective values were 12%, 25%, and 20%. About 43% of the
      immobilized cadmium remained in roots after sequential extraction, and
      bioaccumulation factors in shoots had the same values independently of Cd
      concentration. At both Cd concentrations, the cadmium translocation index for F.
      ovina was low (< 1), which is why this grass can be recommended for
      phytostabilization of the metal under study.

PMID- 28517922
TI  - Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.

PMID- 28517923
TI  - Prevalence of Parasitic Contaminationin Salad Vegetables Collected from
      Supermarkets and Street Vendorsin Amman and Baqa'a - Jordan.
AB  - One of the main ways in transmitting parasites to humans is through consuming
      contaminated raw vegetables. The aim of this study was to evaluate the prevalence
      of parasitological contamination (helminthes eggs, Giardia and Entamoeba
      histolytica cysts) of salad vegetables sold at supermarkets and street vendors in
      Amman and Baqa'a - Jordan. A total of 133 samples of salad vegetables were
      collected and examined for the prevalence of parasites. It was found that 29% of
      the samples were contaminated with different parasites. Of the 30 lettuce, 33
      tomato, 42 parsley and 28 cucumber samples examined the prevalence of Ascaris
      spp. eggs was 43%, 15%, 21% and 4%; Toxocara spp. eggs was 30%, 0%, 0% and 4%;
      Giardia spp. cysts was 23%, 6%, 0% and 0%; Taenia/Echinococcus eggs was 20%, 0%,
      5% and 0%; Fasciola hepatica eggs was 13%, 3%, 2% and 0%; and E. histolytica
      cysts was 10%, 6%, 0% and 0%, respectively. There was no significant difference
      in the prevalence of parasite in salad vegetables either between supermarkets and
      street vendors, or between Amman and Baqa'a, Ascaris spp. was found to be the
      highest prevalent parasite in salad vegetables from supermarkets and street
      vendors and from Amman and Baqa'a. Our results pointed out that, the parasitic
      contamination of salad vegetables found in our study might be caused by
      irrigating crops with faecal contaminated water. We concluded that salad
      vegetables sold in Amman and Baqa'a may cause a health risk to consumers.

PMID- 28517924
TI  - Informed Consent.

PMID- 28517925
TI  - Informed Consent.

PMID- 28517926
TI  - Laser-Induced Population Inversion in Rhodamine 6G for Lysozyme Oligomer
      Detection.
AB  - Fluorescence spectroscopy is a common method for detecting amyloid fibrils in
      which organic fluorophores are used as markers that exhibit an increase in
      quantum yield upon binding. However, most of the dyes exhibit enhanced emission
      only when bound to mature fibrils, and significantly weaker signals are obtained
      in the presence of amyloid oligomers. In the concept of population inversion, a
      laser is used as an excitation source to keep the major fraction of molecules in
      the excited state to create the pathways for the occurrence of stimulated
      emission. In the case of the proteins, the conformational changes lead to the
      self-ordering and thus different light scattering conditions that can influence
      the optical signatures of the generated light. Using this methodology, we show it
      is possible to optically detect amyloid oligomers using commonly available
      staining dyes in which population inversion can be induced. The results indicate
      that rhodamine 6G molecules are complexed with oligomers, and using a laser
      assisted methodology, weakly emissive states can be detected. Significant
      spectral red-shifting of rhodamine 6G dispersed with amyloid oligomers and a
      notable difference determined by comparison of spectra of the fibrils suggest the
      existence of specific dye aggregates around the oligomer binding sites. This
      approach can provide new insights into intermediate oligomer states that are
      believed to be responsible for toxic seeding in neurodegeneration diseases.

PMID- 28517927
TI  - Stable High-Performance Flexible Photodetector Based on Upconversion
      Nanoparticles/Perovskite Microarrays Composite.
AB  - Methylammonium lead halide perovskite has emerged as a new class of low
      temperature-processed high-performance semiconductors for optoelectronics, but
      with photoresponse limited to the UV-visible region and low environmental
      stability. Herein, we report a flexible planar photodetector based on MAPbI3
      microarrays integrated with NaYF4:Yb/Er upconversion nanoparticles (UCns) that
      offers promise for future high performance and long-term environmental stability.
      The promise derives from the confluence of several factors, including
      significantly enhanced photons absorption in the visible spectrum, efficient
      energy transition in the near-infrared (NIR) region, and inhibition of water
      attack by the hydrophobic UCns capping layer. The UCns layer aided in remarkably
      enhanced photodetection capability in the visible spectrum with detectivity (D*)
      reaching 5.9 * 1012 Jones, among the highest reported values, due to the
      increased photocarrier lifetime and decreased reflectivity. Excellent NIR
      photoresponse with spectral responsivity (R) and D* as high as 0.27 A W-1 and
      0.76 * 1012 Jones were obtained at 980 nm, respectively, superior to the reported
      values of state-of-the-art organic-perovskite NIR photodetectors. Moreover, the
      hydrophobic UCns capping layer serving as a moisture inhibitor allowed
      significantly enhanced long-term environmental stability, e.g., 70% vs 27%
      performance retained after 1000 h exposure in 30-40% RH humidity air without
      encapsulation for the bilayer and the neat MAPbI3 devices, respectively. These
      results suggest that the composite based on perovskite and UCns is promising for
      constructing high-performance broadband optoelectronic devices with long-term
      stability.

PMID- 28517928
TI  - Integrated Modeling of Survival Data from Multiple Stressor Ecotoxicology
      Experiments.
AB  - Ecotoxicological assessments often focus on the response of an organism to an
      individual contaminant under standardized laboratory conditions. Under more
      ecologically realistic conditions, however, individuals are likely to be exposed
      to a range of environmental conditions that have the potential to act as
      additional stressors. Multiple-stressor experiments improve our understanding of
      an organism's response to a toxicant under ecologically relevant conditions and
      provide realistic risk assessment data. To date, there is no standardized method
      for analyzing multiple-stressor data using dose-response regression. We present a
      reliable technique to assess for the effects of additional stressors on an LCx
      estimate in a consistent framework, providing interpretable results that
      meaningfully deal with environmental changes and their possible impacts on
      sensitivity estimates to a toxicant. The method is applicable to any data set
      where toxicity tests are conducted at varying levels of one or more additional
      stressors. We illustrate the method with data from an experiment that
      investigates the effects of salinity and temperature on the sensitivity of the
      subantarctic isopod Limnoria stephenseni to copper, where it is shown that the
      major change in the LC50 can be primarily attributed to a specific temperature
      increase. This method has been incorporated into an R package available at
      github.com/ahproctor/LC50.

PMID- 28517929
TI  - Computational Modeling and Simulation of CO2 Capture by Aqueous Amines.
AB  - We review the literature on the use of computational methods to study the
      reactions between carbon dioxide and aqueous organic amines used to capture CO2
      prior to storage, reuse, or sequestration. The focus is largely on the use of
      high level quantum chemical methods to study these reactions, although the review
      also summarizes research employing hybrid quantum mechanics/molecular mechanics
      methods and molecular dynamics. We critically review the effects of basis set
      size, quantum chemical method, solvent models, and other factors on the accuracy
      of calculations to provide guidance on the most appropriate methods, the expected
      performance, method limitations, and future needs and trends. The review also
      discusses experimental studies of amine-CO2 equilibria, kinetics, measurement and
      prediction of amine pKa values, and degradation reactions of aqueous organic
      amines. Computational simulations of carbon capture reaction mechanisms are also
      comprehensively described, and the relative merits of the zwitterion,
      termolecular, carbamic acid, and bicarbonate mechanisms are discussed in the
      context of computational and experimental studies. Computational methods will
      become an increasingly valuable and complementary adjunct to experiments for
      understanding mechanisms of amine-CO2 reactions and in the design of more
      efficient carbon capture agents with acceptable cost and toxicities.

PMID- 28517930
TI  - Middle-Down 193-nm Ultraviolet Photodissociation for Unambiguous Antibody
      Identification and its Implications for Immunoproteomic Analysis.
AB  - Mass spectrometry (MS) has emerged as a powerful tool within the growing field of
      immunoproteomics, which aims to understand antibody-mediated immunity at the
      molecular-level based on the direct determination of serological antibody
      repertoire. To date, these methods have relied on the use of high-resolution
      bottom-up proteomic strategies that require effective sampling and
      characterization of low abundance peptides derived from the antigen-binding
      domains of polyclonal antibody mixtures. Herein, we describe a method that uses
      restricted Lys-C enzymatic digestion to increase the average mass of proteolytic
      IgG peptides (>=4.5 kDa) and produce peptides which uniquely derive from single
      antibody species. This enhances the capacity to discriminate between very similar
      antibodies present within polyclonal mixtures. Furthermore, our use of 193-nm
      ultraviolet photodissociation (UVPD) improves spectral coverage of the antibody
      sequence relative to conventional collision- and electron-based fragmentation
      methods. We apply these methods to both a monoclonal and an antibody mixture. By
      identifying from a database search of approximately 15 000 antibody sequences
      those which compose the mixture, we demonstrate the analytical potential of
      middle-down UVPD for MS-based serological repertoire analysis.

PMID- 28517931
TI  - Correction to Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure
      of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1
      gp120.

PMID- 28517932
TI  - Mechanism of Discrimination of 8-Oxoguanosine versus Guanosine by Escherichia
      coli Fpg.
AB  - The mutagenic 8-oxoguanosine monophosphate, the predominant product of DNA
      oxidation, is excised by formamidopyrimidine glycosylase (Fpg) in bacteria. The
      mechanism of recognition of 8-oxodG, which differs subtly from its normal
      counterpart, guanosine monophosphate (dG), by Escherichia coli Fpg remains
      elusive due to the lack of structural data of E. coli Fpg bound to 8-oxodG. Here,
      we present solution-state structure of 8-oxodG oligomer bound to E. coli E3Q Fpg
      using UV resonance Raman (UVRR) spectroscopy. The vibrational spectra report on
      the pi-stacking and hydrogen bonding interactions established by 8-oxodG with E.
      coli E3Q Fpg. Furthermore, we report on the interactions of E. coli E3Q Fpg with
      the normal, undamaged nucleotide, dG. We show that E. coli Fpg recognizes 8-oxodG
      and dG through their C2-amino group but only 8-oxodG forms extensive contacts
      with E. coli Fpg. Our findings provide a basis for mechanism of lesion
      recognition by E. coli Fpg.

PMID- 28517933
TI  - Ag-Catalyzed Oxidative Cyclization Reaction of 1,6-Enynes and Sodium Sulfinate:
      Access to Sulfonylated Benzofurans.
AB  - A convenient protocol for the synthesis of sulfonylated benzofurans via Ag
      catalyzed oxidative cyclization has been established. Chemically stable and
      easily available sodium sulfinates were used as the sulfonylation reagents and
      building block for the heterocycle construction. With this novel strategy,
      various benzofurans bearing dual functional groups could be obtained in good
      yields with high chemo- and regioselectivities under mild conditions.

PMID- 28517936
TI  - In Situ Hydrogel Conditioning of Tissue Samples To Enhance the Drug's Sensitivity
      in Ambient Mass Spectrometry Imaging.
AB  - Ion suppression from the tissue matrix has a severe effect on the mass
      spectrometry imaging (MSI) of drugs. This problem hinders further applications of
      MSI in preclinical drug research and development. In this study, an in situ
      hydrogel conditioning method was developed to enhance the sensitivity of air-flow
      assisted desorption electrospray ionization (AFADESI)-MSI. Instead of the
      traditional washing or digestion treatment in solvent, this method used a solid
      phase hydrogel to "wash" tissue sections. It was demonstrated that this in situ
      hydrogel conditioning method improved the drug signal by as much as 2- to 25-fold
      in MSI, especially for hydrophobic compounds. Furthermore, the obvious
      dislocation of analytes was not observed. The evaluation of spatial resolution
      indicated that the amount of dislocation in tissue sections with the hydrogel
      process was less than the resolution of AFADESI-MSI. The underlying reasons for
      the MSI signal enhancement were initially investigated. The decreased signal
      intensities of choline, betaine, and carnitine and the increased intensities of
      the [M + H]+/[M + Na]+ and [M + H]+/[M + K]+ ratios for drugs in the mass spectra
      of pretreated tissues provided evidence that this method can reduce the levels of
      highly competitive quaternary ammonium and inorganic salts in the tissues. The
      preformation of a thin liquid film for droplet pickup would also raise the
      ionization efficiency of drugs. These results demonstrated that this in situ
      hydrogel conditioning method provides a rapid and feasible approach to improving
      the sensitivity of ambient MSI for drug mapping in tissues.

PMID- 28517935
TI  - Regio- and Stereoselective Radical Perfluoroalkyltriflation of Alkynes Using
      Phenyl(perfluoroalkyl)iodonium Triflates.
AB  - A method for regio- and stereoselective anti-addition of the perfluoroalkyl and
      the triflate group of phenyl(perfluoroalkyl)iodonium triflates to alkynes is
      presented. The radical reaction uses cheap CuCl as a smart initiator and can be
      conducted in gram scale. The perfluoroalkyltriflated products are readily further
      functionalized, rendering this transformation valuable.

PMID- 28517934
TI  - Plasma and Serum Metabolite Association Networks: Comparability within and
      between Studies Using NMR and MS Profiling.
AB  - Blood is one of the most used biofluids in metabolomics studies, and the serum
      and plasma fractions are routinely used as a proxy for blood itself. Here we
      investigated the association networks of an array of 29 metabolites identified
      and quantified via NMR in the plasma and serum samples of two cohorts of ~1000
      healthy blood donors each. A second study of 377 individuals was used to extract
      plasma and serum samples from the same individual on which a set of 122
      metabolites were detected and quantified using FIA-MS/MS. Four different
      inference algorithms (ARANCE, CLR, CORR, and PCLRC) were used to obtain consensus
      networks. The plasma and serum networks obtained from different studies showed
      different topological properties with the serum network being more connected than
      the plasma network. On a global level, metabolite association networks from
      plasma and serum fractions obtained from the same blood sample of healthy people
      show similar topologies, and at a local level, some differences arise like in the
      case of amino acids.

PMID- 28517937
TI  - Cellular Shuttles: Monocytes/Macrophages Exhibit Transendothelial Transport of
      Nanoparticles under Physiological Flow.
AB  - A major hurdle in the development of biomedical nanoparticles (NP) is
      understanding how they interact with complex biological systems and navigate
      biological barriers to arrive at pathological targets. It is becoming
      increasingly evident that merely controlling particle physicochemical properties
      may not be sufficient to mediate particle biodistribution in dynamic
      environments. Thus, researchers are increasingly turning toward more complex but
      likewise more physiological in vitro systems to study particle--cell/particle
      system interactions. An emerging paradigm is to utilize naturally migratory cells
      to act as so-called "Trojan horses" or cellular shuttles. We report here the use
      of monocytes/macrophages to transport NP across a confluent endothelial cell
      layer using a microfluidic in vitro model. With a custom-built flow chamber, we
      showed that physiological shear stress, when compared to low flow or static
      conditions, increased NP uptake by macrophages. We further provided a
      mathematical explanation for the effect of flow on NP uptake, namely that the
      physical exposure times of NP to cells is dictated by shear stress (i.e., flow
      rate) and results in increased particle uptake under flow. This study was
      extended to a multicellular, hydrodynamic in vitro model. Because monocytes are
      cells that naturally translocate across biological barriers, we utilized a
      monocyte/macrophage cell line as cellular NP transporters across an endothelial
      layer. In this exploratory study, we showed that monocyte/macrophage cells adhere
      to an endothelial layer and dynamically interact with the endothelial cells. The
      monocytes/macrophages took up NP and diapedesed across the endothelial layer with
      NP accumulating within the cellular uropod. These data illustrate that
      monocytes/macrophages may therefore act as active shuttles to deliver particles
      across endothelial barriers.

PMID- 28517939
TI  - Breakdown of Optical Phonons' Splitting in Two-Dimensional Materials.
AB  - We investigate the long-wavelength dispersion of longitudinal and transverse
      optical phonon modes in polar two-dimensional materials, multilayers, and their
      heterostructures. Using analytical models and density-functional perturbation
      theory in a two-dimensional framework, we show that at variance with the three
      dimensional case these modes are degenerate at the zone center but the
      macroscopic electric field associated with the longitudinal-optical modes gives
      rise to a finite slope at the zone center in their corresponding phonon
      dispersions. This slope increases linearly with the number of layers and it is
      determined solely by the Born effective charges of the material and the
      dielectric properties of the surrounding media. Screening from the environment
      can greatly reduce the slope splitting between the longitudinal and transverse
      optical modes and can be seen in the experimentally relevant case of boron
      nitride-graphene heterostructures. As the phonon momentum increases, the
      intrinsic screening properties of the two-dimensional material dictate the
      transition to a momentum-independent splitting similar to that of three
      dimensional materials. These considerations are essential to understand
      electrical transport and optical coupling in two-dimensional systems.

PMID- 28517938
TI  - Glutamate Ligation in the Ni(II)- and Co(II)-Responsive Escherichia coli
      Transcriptional Regulator, RcnR.
AB  - Escherichia coli RcnR (resistance to cobalt and nickel regulator, EcRcnR) is a
      metal-responsive repressor of the genes encoding the Ni(II) and Co(II) exporter
      proteins RcnAB by binding to PRcnAB. The DNA binding affinity is weakened when
      the cognate ions Ni(II) and Co(II) bind to EcRcnR in a six-coordinate site that
      features a (N/O)5S ligand donor-atom set in distinct sites: while both metal ions
      are bound by the N terminus, Cys35, and His64, Co(II) is additionally bound by
      His3. On the other hand, the noncognate Zn(II) and Cu(I) ions feature a lower
      coordination number, have a solvent-accessible binding site, and coordinate
      protein ligands that do not include the N-terminal amine. A molecular model of
      apo-EcRcnR suggested potential roles for Glu34 and Glu63 in binding Ni(II) and
      Co(II) to EcRcnR. The roles of Glu34 and Glu63 in metal binding, metal
      selectivity, and function were therefore investigated using a structure/function
      approach. X-ray absorption spectroscopy was used to assess the structural changes
      in the Ni(II), Co(II), and Zn(II) binding sites of Glu -> Ala and Glu -> Cys
      variants at both positions. The effect of these structural alterations on the
      regulation of PrcnA by EcRcnR in response to metal binding was explored using
      LacZ reporter assays. These combined studies indicate that while Glu63 is a
      ligand for both metal ions, Glu34 is a ligand for Co(II) but possibly not for
      Ni(II). The Glu34 variants affect the structure of the cognate metal sites, but
      they have no effect on the transcriptional response. In contrast, the Glu63
      variants affect both the structure and transcriptional response, although they do
      not completely abolish the function of EcRcnR. The structure of the Zn(II) site
      is not significantly perturbed by any of the glutamic acid variations. The
      spectroscopic and functional data obtained on the mutants were used to calculate
      models of the metal-site structures of EcRcnR bound to Ni(II), Co(II), and
      Zn(II). The results are interpreted in terms of a switch mechanism, in which a
      subset of the metal-binding ligands is responsible for the allosteric response
      required for DNA release.

PMID- 28517940
TI  - Thermal Decomposition of Potential Ester Biofuels. Part I: Methyl Acetate and
      Methyl Butanoate.
AB  - Two methyl esters were examined as models for the pyrolysis of biofuels. Dilute
      samples (0.06-0.13%) of methyl acetate (CH3COOCH3) and methyl butanoate
      (CH3CH2CH2COOCH3) were entrained in (He, Ar) carrier gas and decomposed in a set
      of flash-pyrolysis microreactors. The pyrolysis products resulting from the
      methyl esters were detected and identified by vacuum ultraviolet photoionization
      mass spectrometry. Complementary product identification was provided by matrix
      infrared absorption spectroscopy. Pyrolysis pressures in the pulsed microreactor
      were about 20 Torr and residence times through the reactors were roughly 25-150
      MUs. Reactor temperatures of 300-1600 K were explored. Decomposition of CH3COOCH3
      commences at 1000 K, and the initial products are (CH2?C?O and CH3OH). As the
      microreactor is heated to 1300 K, a mixture of CH2?C?O and CH3OH, CH3, CH2?O, H,
      CO, and CO2 appears. The thermal cracking of CH3CH2CH2COOCH3 begins at 800 K with
      the formation of CH3CH2CH?C?O and CH3OH. By 1300 K, the pyrolysis of methyl
      butanoate yields a complex mixture of CH3CH2CH?C?O, CH3OH, CH3, CH2?O, CO, CO2,
      CH3CH?CH2, CH2CHCH2, CH2?C?CH2, HCCCH2, CH2?C?C?O, CH2?CH2, HC=CH, and CH2?C?O.
      On the basis of the results from the thermal cracking of methyl acetate and
      methyl butanoate, we predict several important decomposition channels for the
      pyrolysis of fatty acid methyl esters, R-CH2-COOCH3. The lowest-energy
      fragmentation will be a 4-center elimination of methanol to form the ketene
      RCH?C?O. At higher temperatures, concerted fragmentation to radicals will ensue
      to produce a mixture of species: (RCH2 + CO2 + CH3) and (RCH2 + CO + CH2?O + H).
      Thermal cracking of the beta C-C bond of the methyl ester will generate the
      radicals (R and H) as well as CH2?C?O + CH2?O. The thermochemistry of methyl
      acetate and its fragmentation products were obtained via the Active
      Thermochemical Tables (ATcT) approach, resulting in DeltafH298(CH3COOCH3) = -98.7
      +/- 0.2 kcal mol-1, DeltafH298(CH3CO2) = -45.7 +/- 0.3 kcal mol-1, and
      DeltafH298(COOCH3) = -38.3 +/- 0.4 kcal mol-1.

PMID- 28517941
TI  - Cognitive and affective factors predicting daily somatic complaints in college
      students.
AB  - Evidence suggests that cumulative somatic complaints predict health care
      utilization in college students. The symptom perception hypothesis and the
      response expectancy theory are 2 theories concerning the generation of somatic
      complaints. The symptom perception hypothesis suggests that negative affect
      influences daily somatic complaints, whereas the response expectancy theory
      surmises somatic complaint generation relates to response expectancies. Some
      evidence suggests that understanding the complex interplay of these factors may
      enhance prediction of daily somatic complaints. This study examines the combined
      effects of state negative affect, trait negative affect, and response
      expectancies in predicting daily somatic complaints. A total of 95 college
      students took part in a 2-part study composed of 1 in-lab session followed by
      completion of up to 7 daily diaries. Results show that state negative affect,
      trait negative affect, and response expectancies all uniquely predict daily
      somatic complaints. Our results support a cognitive-affective basis for somatic
      complaints and suggest future research integrating biopsychosocial factors may be
      useful in increasing our understanding. Furthermore, our results suggest
      potential intervention targets when counseling college students experiencing
      somatic complaints without physical origins. (PsycINFO Database Record

PMID- 28517943
TI  - Implications of parent-child relationships for emerging adults' subjective
      feelings about adulthood.
AB  - Little is known about the role of parents in promoting their children's
      successful transition to adulthood, particularly for college students who may
      maintain stronger ties to parents than other emerging adults. The present study
      therefore investigated longitudinal implications of parent-child relationship
      qualities during emerging adults' first year of college for their feelings about
      the upcoming transition to adulthood 3 years later, as well as implications of 3
      types of parental control (behavioral control, psychological control, helicopter
      parenting) for these associations. Multilevel models indicated that emerging
      adults who reported less negativity in their relationships with mothers and
      fathers felt more like adults 3 years later compared with emerging adults with
      low-quality relationships, while high levels of psychological control and
      helicopter parenting had detrimental implications for their vocational identity
      development and perceived competence regarding their transition to adulthood.
      However, nuanced interactions between parent-child relationship quality and
      parental control indicated that behavioral control had positive implications for
      outcomes if it occurred within the context of high-quality relationships, or when
      utilized with sons. The present study highlights the complex role that parents
      may play during college students' transition to adulthood, and future work should
      continue to examine ways that clinicians can incorporate parents as a potential
      resource for promoting emerging adults' successful transition to adulthood and
      the workforce. (PsycINFO Database Record

PMID- 28517942
TI  - Cognitive bias and paw preference in the domestic dog (Canis familiaris).
AB  - Limb use, an indicator of hemispheric functioning, may be a useful predictor of
      cognitive bias and hence vulnerability to welfare risk. The relationship between
      cognitive bias and motor asymmetry, however, has been subject to little
      investigation. This study explored the association between motor asymmetry and
      cognitive bias in the domestic dog, a species that displays lateral bias in the
      form of paw preferences and exhibits positive and negative affective states.
      Thirty pet dogs had their paw preferences assessed using the Kong ball test. The
      subjects' affective state was assessed using a cognitive bias test in which the
      animals' latency to approach a bowl placed in 1 of 3 ambiguous positions was
      recorded. Animals veering more toward a left-paw preference were found to be
      significantly slower to approach the bowl placed in 1 of the ambiguous positions
      than ambilateral or right-pawed dogs. Left-pawed subjects approached the bowl
      located at the 3 ambiguous positions at roughly the same speed, while ambilateral
      and right-pawed animals became increasingly slower to approach the bowl the
      further it was located from the baited food bowl. The study points to a possible
      relationship between cognitive bias and paw preference in the dog, with left
      pawed animals being more negative or "pessimistic" in their cognitive outlook
      than right-pawed or ambilateral individuals. It is proposed that limb preference
      testing might offer a more practical and straightforward way of identifying
      individuals at risk from poor welfare by virtue of how they perceive the world
      than more time-consuming cognitive bias tests. (PsycINFO Database Record

PMID- 28517944
TI  - Attitudes toward and prevalence of extramarital sex and descriptions of
      extramarital partners in the 21st century.
AB  - Using the most recent nine waves of data from the General Social Survey, which
      consists of in-person interviews of independent probability samples of the adult
      household population of the United States, the purposes of this study were to (a)
      provide descriptive information on adults' attitudes toward extramarital sex,
      lifetime and annual prevalence of extramarital sex among ever-married adults, and
      the identity of the extramarital sex partner(s) of currently married adults; (b)
      evaluate temporal trends in attitudes toward and prevalence of extramarital sex
      from 2000 to 2016; and (c) test for gender differences in attitudes toward and
      prevalence of extramarital sex and descriptions of the extramarital partner. The
      percentages of Americans who reported that extramarital sex was always wrong
      significantly declined from 2000 to 2016, whereas the percentage who reported it
      was wrong only sometimes significantly increased. There was a statistically
      significant linear decline in reported lifetime prevalence of extramarital sex
      from 2000 (17.8%) to 2016 (16.3%), whereas there was no statistically significant
      change in reported annual prevalence of extramarital sex (3.0%). People most
      commonly reported having extramarital sex with a close personal friend (53.5%) or
      neighbor, coworker, or long-term acquaintance (29.4%). Compared with women, men
      were (a) less likely to report that extramarital sex was always wrong and more
      likely to view it as almost always wrong, wrong only sometimes, or not wrong at
      all; (b) more likely to report past-year and lifetime extramarital sex; and (c)
      more likely to report extramarital sex with someone they knew casually. (PsycINFO
      Database Record

PMID- 28517945
TI  - Predicting growth in English and French vocabulary: The facilitating effects of
      morphological and cognate awareness.
AB  - The present study investigated the contribution of morphological and cognate
      awareness to the development of English and French vocabulary knowledge among
      young minority and majority language children who were enrolled in a French
      immersion program. Participating children (n = 75) were assessed in English and
      French on measures of morphological awareness, cognate awareness, and vocabulary
      knowledge from Grades 1 to 3. Hierarchical linear modeling was used to
      investigate linear trends in English and French vocabulary growth for minority
      and majority language children and to identify metalinguistic contributions to
      Grade 1 and Grade 3 English and French vocabulary performance and rate of growth.
      Results demonstrated a similar pattern of prediction for both groups of children.
      English and French morphological awareness and French-English cognate awareness
      significantly predicted concurrent and longitudinal vocabulary development after
      controlling for nonverbal reasoning, phonological awareness, and word
      identification. The contributions of morphological awareness to English
      vocabulary and cognate awareness to French vocabulary strengthened between Grades
      1 and 2. These findings highlight the emerging importance of morphological and
      cognate awareness in children's vocabulary development and suggest that these
      metalinguistic factors can serve to broaden the vocabulary repertoire of children
      who enter school with limited language proficiency. (PsycINFO Database Record

PMID- 28517946
TI  - Why be moral? Moral identity motivation and age.
AB  - Moral identity research to date has largely failed to provide evidence for
      developmental trends in moral identity, presumably because of restrictions in the
      age range of studies and the use of moral identity measures that are insensitive
      to age-related change. The present study investigated moral identity motivation
      across a broad age range (14-65 years, M = 33.48; N = 252) using a modified
      version of the Good Self-Assessment Interview. Individuals' moral identity
      motivation was coded and categorized as external, internal, or relationship
      oriented. It was found that with age, external moral identity motivation
      decreased, whereas internal moral identity motivation increased. Effects of age
      were stronger in adolescence and emerging adulthood than in young adulthood and
      middle age. Findings underscore the developmental nature of the moral identity
      construct and suggest that moral motivation becomes more self-integrated with
      age. (PsycINFO Database Record

PMID- 28517947
TI  - Intolerance of uncertainty predicts increased striatal volume.
AB  - Oversensitivity to uncertain future threat is usefully conceptualized as
      intolerance of uncertainty (IU). Neuroimaging studies of IU to date have largely
      focused on its relationship with brain function, but few studies have documented
      the association between IU and the quantitative properties of brain structure.
      Here, we examined potential gray and white-matter brain structural correlates of
      IU from 61 healthy participants. Voxel-based morphometric analysis highlighted a
      robust positive correlation between IU and striatal volume, particularly the
      putamen. Conversely, tract-based spatial statistical analysis showed no evidence
      for a relationship between IU and the structural integrity of white-matter fiber
      tracts. Current results converge upon findings from individuals with anxiety
      disorders such as obsessive-compulsive disorder (OCD) or generalized anxiety
      disorder (GAD), where abnormally increased IU and striatal volume are
      consistently reported. They also converge with neurobehavioral data implicating
      the putamen in predictive coding. Most notably, the relationship between IU and
      striatal volume is observed at a preclinical level, suggesting that the
      volumetric properties of the striatum reflect the processing of uncertainty per
      se as it relates to this dimensional personality characteristic. Such a
      relationship could then potentially contribute to the onset of OCD or GAD, rather
      than being unique to their pathophysiology. (PsycINFO Database Record

PMID- 28517948
TI  - Randomized controlled trial of an internet cognitive behavioral skills-based
      program for auditory hallucinations in persons with psychosis.
AB  - OBJECTIVE: Despite strong evidence supporting the effectiveness of cognitive
      behavioral therapy for psychosis (CBTp), most clinicians in the United States
      have received little or no training in the approach and access remains very low,
      indicating a potential role for technology in increasing access to this
      intervention. Coping With Voices (CWV) is a 10-session, interactive, Web-based
      CBTp skills program that was developed to meet this need, and was shown to be
      feasible and associated with reduced severity of auditory hallucinations in a
      previous pilot study. To more rigorously evaluate this program, a randomized
      controlled trial was conducted comparing the efficacy of CWV to usual care (UC).
      METHOD: The trial was conducted with a sample of 37 community mental health
      center clients with schizophrenia and moderate-to-severe auditory hallucinations,
      with assessments conducted at baseline, posttreatment, and 3-month follow-up.
      RESULTS: Engagement in and satisfaction with the CWV program were high. Both the
      CWV and UC groups improved comparably in severity of auditory hallucinations and
      other symptoms over the treatment and at follow-up. However, participants in the
      CWV program showed significantly greater increases in social functioning and in
      knowledge about CBTp. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The results
      suggest that the CWV program has promise for increasing access to CBTp, and
      associated benefits in the management of distressing psychotic symptoms and
      improving social functioning. (PsycINFO Database Record

PMID- 28517949
TI  - Cognitive-behavioral treatments for criminogenic thinking: Barriers and
      facilitators to implementation within the Veterans Health Administration.
AB  - Cognitive-behavioral treatments for criminogenic thinking (i.e., antisocial
      cognitions, attitudes, and traits) are regarded as best practices for reducing
      criminal recidivism among justice-involved adults. However, the barriers and
      facilitators to implementation of these treatments within large health care
      systems such as the Veterans Health Administration (VHA) are largely unknown. To
      address this gap, we conducted qualitative interviews with 22 Specialists from
      the VHA's Veterans Justice Programs who had been trained in a cognitive
      behavioral treatment for criminogenic thinking (i.e., Moral Reconation Therapy
      [MRT], Thinking for a Change [T4C]). The time-intensiveness of these treatments
      emerged as a barrier to implementation. Potential solutions identified were
      patient incentives for treatment engagement, streamlining the curriculum, and
      implementing the treatments within long-term/residential programs. At the program
      level, providers' stigma/bias toward patients with antisocial tendencies was seen
      as a barrier to implementation, as were time/resource constraints on providers.
      To address the latter, use of peer providers to deliver the treatments and
      partnerships between justice programs and behavioral health services were
      suggested. At the system level, lack of recognition of criminogenic treatments as
      evidence based, and uncertainty of sustained funds to support ongoing costs of
      these treatments emerged as implementation barriers. To address the latter, a
      train-the-trainers model was suggested. Our findings serve as a guide for
      implementation of criminogenic treatments for providers and policymakers in VHA
      and other large health care systems, which are increasingly called upon to
      provide care to justice-involved adults in the community. (PsycINFO Database
      Record

PMID- 28517950
TI  - Gender differences in service utilization among Operations Enduring Freedom,
      Iraqi Freedom, and New Dawn Veterans Affairs patients with severe mental illness
      and substance use disorders.
AB  - Severe mental illness (SMI) and substance use disorders (SUD) are among the more
      chronic and costly mental health conditions treated in the Department of Veterans
      Affairs (VA). Service use patterns of returning veterans with SMI and SUD have
      received little attention. We examined gender differences in the utilization of
      VA services among a national sample of Operations Enduring Freedom, Iraqi
      Freedom, and New Dawn (OEF/OIF/OND) VA patients with SMI, SUD, and their
      comorbidity (SMI/SUD) in their first year of established VA care (N = 24,166).
      Outpatient services and acute-residential stays were modeled using negative
      binomial and logistic regression, respectively. Among all diagnostic categories,
      men used outpatient services less often than did women, including primary care
      (adjusted rate ratio [ARR] = .71, 95% confidence interval CI [.68, .74]), mental
      health (ARR = .85, 95% CI [.80, .91]), and addiction (ARR = .91, 95% CI [.83,
      .99]) services. For emergency department (ED) and psychiatric inpatient services,
      gender interacted significantly with diagnosis. The combination of SMI/SUD
      compared to either SMI or SUD conferred greater risk of ED utilization among men
      than women (adjusted odds ratio [AOR] = 2.09, 95% CI [1.24, 3.51], and 1.95, 95%
      CI [1.17, 3.26], respectively). SMI versus SUD conferred greater risk of
      psychiatric inpatient utilization among men than women (AOR = 1.83, 95% CI [1.43,
      2.34]). Our findings point to gender differences in outpatient and acute service
      utilization among OEF/OIF/OND VA patients with some of the more chronic and
      costly mental health conditions. Further investigation of health care utilization
      patterns is needed to understand factors driving these gender differences to
      ensure that veterans have appropriate access to the services they need. (PsycINFO
      Database Record

PMID- 28517951
TI  - Treatment-as-usual therapy targets for comorbid youth disproportionately focus on
      externalizing problems.
AB  - This study examined whether psychological treatment for youth with comorbid
      externalizing and internalizing disorders targets externalizing rather than
      internalizing pathology. Therapist-reported treatment targets for youth (N = 679)
      with (a) only internalizing diagnoses (n = 195); (b) only externalizing diagnoses
      (n = 314); (c) a primary internalizing diagnosis and at least 1 additional
      externalizing diagnosis (n = 75); and (d) a primary externalizing diagnosis and
      at least 1 additional internalizing diagnosis (n = 95) receiving treatment-as
      usual in a public mental health system of care were examined. Treatment targets
      that appeared significantly more often in the externalizing-only and
      internalizing-only diagnostic groups were empirically determined, and a derived
      proportional measure of these targets was analyzed across all 4 diagnostic
      groups, controlling for effects of additional client and treatment
      characteristics. As required by the target selection method, the proportion of
      externalizing targets selected in treatment was greatest for youth with
      externalizing-only diagnoses and least for youth with internalizing-only
      diagnoses. Importantly, the co-occurrence of a secondary externalizing disorder
      with a primary internalizing disorder resulted in a large increase in the
      proportion of externalizing targets endorsed, whereas the co-occurrence of an
      internalizing disorder with a primary externalizing disorder resulted in a
      comparatively small decrease in the proportion of externalizing targets endorsed.
      Results persisted despite several covariates also predicting increased focus on
      externalizing targets, including male gender and younger age. These findings
      suggest that community therapists tend to prioritize externalizing over
      internalizing problems during treatment for such comorbid youth. Implications for
      practice, research and dissemination/implementation efforts are discussed.
      (PsycINFO Database Record

PMID- 28517953
TI  - ?

PMID- 28517952
TI  - DNA methylation and transcription onset in the brain.
AB  - AIM: The goal of this study was to test the state of methylation of transcription
      start positions in DNA that are actively involved in transcription. MATERIALS &
      METHODS: We used sequential ChIP-bisulfite-sequencing with an antibody to RNpolII
      PS5 to map the state of methylation of actively transcribing transcription start
      sites (TSS). RESULTS: TSS that RNApolII-PS5 physically bind to, are ubiquitously
      unmethylated. TSS that appear to be both heavily methylated and transcriptionally
      active are truly a mixture of unmethylated TSS with bound RNApolII-PS5 in some
      nuclei and unbound methylated TSS in other nuclei. CONCLUSION: TSS DNA
      methylation is universally inconsistent with transcription onset and could
      therefore serve as a digital count of the fraction of nuclei with methylation
      silenced TSS.

PMID- 28517954
TI  - On the Rocks: Microbiological Quality and Microbial Diversity of Packaged Ice in
      Southern California.
AB  - Ice is defined as a food and is frequently used in direct contact with food and
      beverages. Packaged ice is commercially produced and can be easily found in
      grocery and convenience stores. However, the quality and safety of packaged ice
      products is not consistent. The Packaged Ice Quality Control Standards manual
      (PIQCS) published by the International Packaged Ice Association provides the
      quality and processing standards for packaged ice produced by its members.
      Packaged ice produced on the premise of stores (on-site packaged ice) is not
      required to be in compliance with these standards. In this study, packaged ice
      produced by manufacturing plants or by in-store bagger (ISB) machines and on-site
      packaged ice were compared for their microbiological quality and microbial
      diversity. Our results revealed that 19% of the 120 on-site packaged ice samples
      did not meet the PIQCS microbial limit of 500 CFU/mL (or g) and also the absence
      of coliforms and Escherichia coli . Staphylococci were found in 34% of the on
      site packaged ice samples, most likely through contamination from the packaging
      workers. None of the ISB and manufactured packaged ice samples had unacceptable
      microbial levels, and all were devoid of staphylococci. Salmonella was absent in
      all samples analyzed in this study. Microbial community analysis of ice based on
      16S/18S rRNA targeted sequencing revealed a much higher microbial diversity and
      abundance in the on-site packaged ice than in the ISB ice. Proteobacteria,
      especially Alphaproteobacteria and Betaproteobacteria, were the dominant
      bacterial groups in all samples tested. Most of these bacteria were oligotrophic;
      however, a few opportunistic or potential pathogens were found at low levels in
      the on-site packaged ice but not in the ISB packaged ice. The types of microbes
      identified may provide information needed to investigate potential sources of
      contamination. Our data also suggest a need for enforcement of processing
      standards during the on-site packaging of ice.

PMID- 28517955
TI  - The long-term risk of smoking in diabetic patients with stable ischemic heart
      disease treated with intensive medical therapy and lifestyle modification.
AB  - Introduction The long-term risk of smoking in diabetic patients with stable
      ischemic heart disease (SIHD) is unknown. We sought to analyze the impact of
      smoking on outcomes of diabetic patients with SIHD when other cardiovascular risk
      factors are being aggressively treated. Methods The Bypass Angioplasty
      Revascularization Investigation 2 Diabetes (BARI 2D) trial randomized 2368
      diabetics with SIHD to intensive medical therapy (IMT) with prompt
      revascularization or IMT alone. Smoking status was obtained at baseline, 6
      months, and 1, 2, 3, 4 and 5 years. The primary endpoint of interest was all
      cause mortality. Results Of 2360 patients, 33.1% of patients never smoked, 54.4%
      were former smokers, and 12.5% were current smokers. The rate of all-cause
      mortality was greater for current (2.5 deaths/100 patient-years) and former
      smokers (3.1 deaths/100 patient-years) than never smokers (2.1 deaths/100 patient
      years) (P = 0.007). Cardiac death, cardiovascular death, fatal or nonfatal
      myocardial infarction, and fatal or nonfatal stroke were not increased in current
      or former smokers compared with never smokers. Compared with never smokers,
      current smokers experienced a 49% increased hazard of death (Hazard Ratio (HR)
      1.49, 95% Confidence Interval (CI): 0.97-2.29, P = 0.07) whereas former smokers
      had a 37% increased hazard of death (HR 1.37, 95% CI: 1.04-2.79, P = 0.02) when
      considering smoking status as a time-dependent variable and adjusting for factors
      that differed by smoking status. Conclusions Current and former smoking are
      associated with increased all-cause mortality in diabetics with SIHD but not with
      increased cardiovascular morbidity or mortality.

PMID- 28517956
TI  - The longitudinal association between anxiety and Internet addiction in
      adolescence: The moderating effect of classroom extraversion.
AB  - Background and aims The risk effect of anxiety on addictive behaviors, including
      Internet addiction (IA), has repeatedly been highlighted in the international
      literature. However, there is a lack of longitudinal studies examining this
      association in relation to proximal context effects, particularly in adolescence.
      Such findings would shed light on potential age- and proximal context-related
      variations in the anxiety-IA association that could better inform IA prevention
      and intervention initiatives. Methods In this study, 648 adolescents, embedded in
      34 classrooms, were assessed at the age of 16 and again at the age of 18 to
      examine the effect of anxiety on IA behaviors in relation to the average level of
      classroom extraversion. IA was assessed with the Internet Addiction Test (Young,
      1998), anxiety with the relevant subscale of the Symptom Checklist 90 - Revised
      (Derogatis & Savitz, 1999) and classroom extraversion with the synonymous
      subscale of the Five Factor Questionnaire (Asendorpf & van Aken, 2003). A three
      level hierarchical linear model was calculated. Results The present findings
      demonstrated that: (a) higher levels of anxiety were significantly associated
      with higher IA behaviors, (b) the strength of this association did not vary over
      time (between 16 and 18 years old), and (c) however, it tended to weaken within
      classrooms higher in extraversion. Discussion This study indicated that the
      contribution of individual IA risk factors might differently unfold within
      different contexts.

PMID- 28517957
TI  - Novel drug and soluble target tolerant antidrug antibody assay for therapeutic
      antibodies bearing the P329G mutation.
AB  - AIM: Bridging immunoassays for detection of antidrug antibodies (ADAs) are
      typically susceptible to high concentrations of residual drug. Sensitive drug
      tolerant assays are, therefore, needed. MATERIALS & METHODS: An immune complex
      assay to detect ADAs against therapeutic antibodies bearing Pro329Gly mutation
      was established. The assay uses antibodies specific for the Pro329Gly mutation
      for capture and human soluble Fcgamma receptor for detection. RESULTS: When
      compared with a bridging assay, the new assay showed similar precision, high
      sensitivity to IgG1 ADA and dramatically improved drug tolerance. However, it was
      not able to detect early (IgM-based) immune responses. CONCLUSION: Applied in
      combination with a bridging assay, the novel assay serves as orthogonal assay for
      immunogenicity assessment and allows further characterization of ADA responses.

PMID- 28517958
TI  - Distance of translation as a predictor of failure of fixation in paediatric
      supracondylar fractures.
AB  - Introduction This study investigates the influence of incomplete reduction of
      supracondylar fractures on the incidence of loss of reduction requiring
      reoperation Materials and methods A review of 107 consecutive patients presenting
      with supracondylar fractures treated with closed reduction and Kirschner wire
      stabilisation, between January 2011 and March 2013, was conducted. The mean age
      was 5 years (range 10 months to 12 years). Pre-, intra- and postoperative
      radiographs were reviewed. All patients who had failure of fixation requiring
      revision surgery were identified. Results Ninety-nine patients had an initial
      adequate radiographic reduction. Of these, one (1%) required revision surgery.
      Eight patients had an initial incomplete radiographic reduction and, of these,
      six (75%) required revision surgery (P < 0.0001). Discussion Supracondylar
      fractures treated with closed reduction and K wire stabilisation require adequate
      intraoperative reduction. Incomplete reduction should not be accepted, as despite
      the bones potential to remodel, the risk of further loss of reduction is high,
      requiring reoperation.

PMID- 28517960
TI  - A Rapid Seedling Resistance Assay Identifies Wild Tomato Lines That Are Resistant
      to Pseudomonas syringae pv. tomato Race 1.
AB  - Bacterial speck caused by Pseudomonas syringae has historically been controlled
      by the Pto/Prf gene cluster. Emerging strains like P. syringae pv. tomato race 1
      overcome resistance conferred by Pto/Prf, and can cause serious crop loss under
      appropriate environmental conditions. We developed a rapid assay to screen wild
      tomato seedlings for resistance to P. syringae pv. tomato race 1. We established
      the seedling resistance assay using the well-characterized P. syringae pv. tomato
      race 0 strain, DC3000, which is recognized in tomato cultivars carrying Pto/Prf
      (PtoR) and causes disease in isogenic lines lacking this cluster (PtoS). We
      optimized infectious conditions for P. syringae on tomato seedlings and
      demonstrated that tomato seedlings respond like adult tomato plants in critical
      measures of susceptibility and immunity, including the hypersensitive response,
      rapid ion leakage, restricted bacterial proliferation, and phenotypic resistance.
      After establishing infectious conditions for P. syringae pv. tomato race 1 on
      tomato seedlings, we screened 96 wild accessions and identified two accessions
      with strong P. syringae pv. tomato race 1 resistance, Solanum neorickii LA1329
      and S. habrochaites LA1253, which are also resistant to bacterial infection as
      adult plants. This rapid high throughput seedling assay has many advantages,
      including reduced plant growth time and large sample sizes, and will allow for
      large-scale screening of resistance in tomato.

PMID- 28517959
TI  - POMICS: A Simulation Disease Model for Timing Fungicide Applications in
      Management of Powdery Mildew of Cucurbits.
AB  - A weather-based simulation model, called Powdery Mildew of Cucurbits Simulation
      (POMICS), was constructed to predict fungicide application scheduling to manage
      powdery mildew of cucurbits. The model was developed on the principle that
      conditions favorable for Podosphaera xanthii, a causal pathogen of this crop
      disease, generate a number of infection cycles in a single growing season. The
      model consists of two components that (i) simulate the disease progression of P.
      xanthii in secondary infection cycles under natural conditions and (ii) predict
      the disease severity with application of fungicides at any recurrent disease
      cycles. The underlying environmental factors associated with P. xanthii infection
      were quantified from laboratory and field studies, and also gathered from
      literature. The performance of the POMICS model when validated with two datasets
      of uncontrolled natural infection was good (the mean difference between simulated
      and observed disease severity on a scale of 0 to 5 was 0.02 and 0.05). In
      simulations, POMICS was able to predict high- and low-risk disease alerts.
      Furthermore, the predicted disease severity was responsive to the number of
      fungicide applications. Such responsiveness indicates that the model has the
      potential to be used as a tool to guide the scheduling of judicious fungicide
      applications.

PMID- 28517961
TI  - Overcoming chemoresistance in cancer stem cells with the help of microRNAs in
      colorectal cancer.
AB  - It has been recognized that acute resistance to chemotherapy mediated by post
      transcriptional and translational control is crucial to influence response and
      survival in cancer treatment. Tumor cells are highly heterogeneous and have the
      ability to adapt a resistance phenotype through epigenetic regulations such as
      microRNAs. This poses a major challenge to the treatment of advanced stage colon
      cancer patients. Colon cancer stem cells have been identified as one of the major
      contributors to resistance of colon cancer to chemotherapy. Through various
      mechanisms, these cells are able to resist the effects of traditional
      chemotherapeutics. The challenge posed by these cells is further enhanced by
      their plastic nature, where cells can transition between non-stem cancer cells
      and cancer stem cells creating a moving target. In this editorial, we discuss
      some of the recent advancements in overcoming chemoresistance associated with
      colon cancer stem cells with the help of microRNAs.

PMID- 28517963
TI  - Novel strategies in vaccine design: can nanocapsules help prevent and treat
      hepatitis B?

PMID- 28517962
TI  - Inhibition of the Continuum of Radiation-Induced Normal Tissue Injury by a Redox
      Active Mn Porphyrin.
AB  - Normal tissue damage after head and neck radiotherapy involves a continuum of
      pathologic events to the mucosa, tongue and salivary glands. We examined the
      radioprotective effects of MnBuOE, a redox-active manganese porphyrin, at three
      stages of normal tissue damage: immediate (leukocyte endothelial cell [L/E]
      interactions), early (mucositis) and late (xerostomia and fibrosis) after
      treatment. In this study, mice received 0 or 9 Gy irradiation to the oral cavity
      and salivary glands +/- MnBuOE treatment. Changes in leukocyte-endothelial cell
      interactions were measured 24 h postirradiation. At 11 days postirradiation,
      mucositis was assessed with a cathepsin-sensitive near-infrared optical probe.
      Stimulated saliva production was quantified at 11 weeks postirradiation. Finally,
      histological analyses were conducted to assess the extent of long-term effects in
      salivary glands at 12 weeks postirradiation. MnBuOE reduced oral mucositis,
      xerostomia and salivary gland fibrosis after irradiation. Additionally, although
      we have previously shown that MnBuOE does not interfere with tumor control at
      high doses when administered with radiation alone, most head and neck cancer
      patients will be treated with the combinations of radiotherapy and cisplatin.
      Therefore, we also evaluated whether MnBuOE would protect tumors against
      radiation and cisplatin using tumor growth delay as an endpoint. Using a range of
      radiation doses, we saw no evidence that MnBuOE protected tumors from radiation
      and cisplatin. We conclude that MnBuOE radioprotects normal tissue at both early
      and late time points, without compromising anti-tumor effects of radiation and
      cisplatin.

PMID- 28517964
TI  - Introductory paragraph.

PMID- 28517965
TI  - BSRM Annual Meeting London - 2015 - Poster & Free Paper Abstracts: Free Paper
      (Podium presentations).

PMID- 28517966
TI  - Abstracts of meeting DCRM November 2016.
AB  - The Netherlands Society of Rehabilitation Medicine (NSRM) represents about 850
      members. Scientific meetings are held twice a year. On 9 and 10 November 2017,
      the NSRM will organise the Dutch Congress of Rehabilitation Medicine (DCRM) in
      cooperation with the Baltic North Sea Forum on Physical and Rehabilitation
      Medicine (BNF-PRM) and the Royal Belgian Society of Physical and Rehabilitation
      Medicine (RBSPRM) in Maastricht, The Netherlands. The theme of this highly
      interactive and interdisciplinary conference is 'Moving ahead towards
      participation'. Abstracts for oral and poster presentations are peer reviewed
      before selection. These ten abstracts were presented and selected for publication
      during DCRM 2016 in The Netherlands. Selection was done by the jury, consisting
      of members of the scientific committee of the NSRM. Contact person within the
      NSRM: AH Vrieling, University Medical Center Groningen, PO Box 30002, 9715 RA,
      Haren, The Netherlands. Email: a.h.vrieling@umcg.nl.

PMID- 28517968
TI  - A community-based qualitative study of intergenerational resilience with
      Palestinian refugee families facing structural violence and historical trauma.
AB  - The purpose of this study was to explore resilience processes in Palestinian
      refugee families living under Israeli occupation for multiple generations.
      Qualitative methods, critical postcolonial theories, and community-based research
      approaches were used to examine intergenerational protective practices and to
      contribute to reconceptualizations of resilience from indigenous perspectives.
      First, the researcher developed a collaborative partnership with a
      nongovernmental organization (NGO) in a UN refugee camp in the occupied West
      Bank. Then, with the support of this NGO, semistructured group and individual
      interviews were completed with a total of 30 participants ( N = 30) ranging in
      age from 18 to 90 years old coming from 5 distinct extended family networks.
      Using grounded theory situational analysis, the findings were organized in a
      representation entitled Palestinian Refugee Family Trees of Resilience (PRFTR).
      These findings explain resilience in terms of three interrelated themes: (a)
      Muqawama/resistance to military siege and occupation; (b) Awda/return to cultural
      roots despite historical and ongoing settler colonialism; and (c)
      Sumoud/perseverance through daily adversities and accumulation of trauma. The
      study findings shed light on how Palestinian families cultivate positive
      adaptation across generations and highlight how incorporating community-based
      perspectives on the historical trauma and violent social conditions of everyday
      life under occupation may be critical for promoting resilience. Results may be
      relevant to understanding the transgenerational transmission of trauma and
      resilience within other displaced communities internationally.

PMID- 28517967
TI  - Cruel to Be Kind: Factors Underlying Altruistic Efforts to Worsen Another
      Person's Mood.
AB  - When aiming to improve another person's long-term well-being, people may choose
      to induce a negative emotion in that person in the short term. We labeled this
      form of agent-target interpersonal emotion regulation altruistic affect worsening
      and hypothesized that it may happen when three conditions are met: (a) The agent
      experiences empathic concern for the target of the affect-worsening process, (b)
      the negative emotion to be induced helps the target achieve a goal (e.g., anger
      for confrontation or fear for avoidance), and (c) there is no benefit for the
      agent. This hypothesis was tested by manipulating perspective-taking instructions
      and the goal to be achieved while participants ( N = 140) played a computer-based
      video game. Participants following other-oriented perspective-taking
      instructions, compared with those following objective perspective-taking
      instructions, decided to induce more anger in a supposed fellow participant who
      was working to achieve a confrontation goal and to induce more fear in a supposed
      fellow participant who was working to achieve an avoidance goal.

PMID- 28517969
TI  - Prevalence and determinants of depression among patients under the care of
      traditional health practitioners in a Kenyan setting: Policy implications.
AB  - In Kenya, there is paucity of information on depression among traditional health
      practitioner (THP) patients, particularly in rural areas. The aim of this study
      was to estimate prevalence and identify determinants of major depressive disorder
      (MDD) among patients of THP in rural Kenya using the World Health Organization
      (WHO) Mental Health Gap Action Programme Intervention Guideline (mhGAP-IG). All
      adult patients seeking care from trained THPs (either traditional healers such as
      diviners and herbalists or faith healers, who use treatments such as prayers,
      laying hands on patients, or providing holy water and ash to their patients) over
      a period of 3 months (September 2014 to November 2014) were screened for
      depression using mhGAP-IG and their sociodemographic characteristics recorded.
      Overall, the prevalence of depression among THP patients was 22.9%. Being older,
      female, single, divorced or separated, as well as unemployment and lack of
      education were found to be significant determinants of depression. Patients with
      MDD frequently presented with suicidal behavior (32.9%, OR = 5.94, p < .0001)
      compared to those that had at least one psychotic symptom (26.3%, OR = 3.65, p <
      .0001). A measure of the accuracy of THPs' assessment of MDD showed 86%
      specificity and 46% sensitivity and the area under receiver operating
      characteristics (ROC) curve was 0.686. Our findings shed light on the prevalence
      of depression among THP patients and thus highlight the need for further research
      on diagnostic tools for use among THPs in order to avoid substandard care and
      promote reliance on more evidence-based methods of care.

PMID- 28517971
TI  - Soft Tissue Changes Around Immediately Placed Implants: A Systematic Review and
      Meta-Analyses With at Least 12 Months of Follow-Up After Functional Loading.
AB  - BACKGROUND: Immediate implant placement (IIP) is predictable but can lead to
      esthetic challenges, including midfacial recession (MFR) and papillary height
      (PH) loss. The aim of this systematic review is to examine the effect of IIP on
      MFR and PH after at least 12 months of functional loading. METHODS: Literature
      review of the Cochrane and MEDLINE electronic databases and hand search up to
      January 2016 identified eligible studies. Four reviewers independently assessed
      data quality and methodology. RESULTS: A total of 106 articles satisfied the
      inclusion criteria. Twelve studies qualified for three meta-analyses. MFR was
      slightly less in conventional implant placement (CIP) than in IIP, but the result
      was not statistically significant (mean difference [MD] -0.064 mm; P = 0.687).
      Similarly, there was better PH maintenance in CIPs, with statistical significance
      for distal PH (DPH) only (cumulative PH: MD -0.396, P = 0.010; DPH: MD -0.765, P
      <0.001; mesial PH [MPH]: MD -0.285, P = 0.256). MFR was slightly less in IIP with
      thick versus thin biotypes, but not statistically significantly different (MD 
      0.373, P = 0.243). Pooled data showed statistically significantly less MFR and
      better PH maintenance in IIP with thick biotype (MFR: MD -0.478, P <0.001;
      cumulative PH: MD -0.287, P <0.001; MPH: MD -0.288, P <0.001; DPH: MD -0.310, P
      <0.001). Non-significantly less MFR (MD 0.253, P = 0.384) and significantly
      better PH maintenance were found in IIP with immediate provisionalization versus
      conventional restoration (MD -0.519, P = 0.028). CONCLUSIONS: IIP in thick
      biotype and with immediate provisionalization had less MFR and better PH than IIP
      in thin biotype or with delayed restoration. However, these findings should be
      interpreted with caution due to high heterogeneity, which was calculated using
      comprehensive meta-analysis statistical software that took into account sample
      size and different treatment groups, and limited qualified studies.

PMID- 28517970
TI  - Osteoblast Progenitors Enhance Osteogenic Differentiation of Periodontal Ligament
      Stem Cells.
AB  - BACKGROUND: Osteoblasts and periodontal ligament stem cells (PDLSCs) play an
      important role in maintaining physiologic function of periodontal tissues and
      participating in periodontal regeneration. Elucidation of interactions between
      osteoblasts and PDLSCs will aid understanding of periodontal regeneration
      mechanisms. This study aims to determine whether preosteoblasts can promote
      osteoblastic/cementoblastic differentiation of PDLSCs. METHODS: PDLSCs were
      cultured alone (control group), or cocultured indirectly with human gingival
      fibroblasts (HGFs) (HGFs group) or MC3T3-E1 cells (OB groups). Alkaline
      phosphatase (ALP) activity and gene/protein expressions levels of ALP, runt
      related transcription factor-2, and osteopontin (OPN) were assessed. Cementum
      attachment protein and cementum protein 23 messenger RNA expressions were also
      evaluated. Bone morphogenetic protein (BMP)-2 secreted by HGFs/MC3T3-E1 cells was
      assessed by enzyme-linked immunosorbent assay. Extracellular matrix calcification
      was measured by staining to quantify calcium content. RESULTS: ALP activity and
      gene/protein expression levels of osteogenic markers were significantly higher in
      the OB groups compared with the HGFs and control groups. Optimal enhancement of
      these parameters occurred at cell ratios of 2:1 to 1:1 (MC3T3-E1:PDLSCs).
      Mineralized nodule formation and calcium content were significantly increased in
      the OB groups compared with the HGF and control groups. The greatest improvement
      took place at the 2:1 (MC3T3-E1:PDLSCs) seeding ratio. BMP-2 from MC3T3-E1
      conditioned medium was significantly and time-dependently increased compared with
      that from HGF-conditioned medium. CONCLUSION: Preosteoblasts can indirectly
      enhance the osteoblastic/cementoblastic differentiation and mineralization of
      PDLSCs with an optimal preosteoblasts:PDLSCs ratio in the range of 2:1 to 1:1.

PMID- 28517972
TI  - Glycated Collagen Stimulates Differentiation of Gingival Myofibroblasts.
AB  - BACKGROUND: Glucose-derived metabolites may alter the structure and biologic
      properties of important proteins in periodontium, such as collagens. As a
      consequence, it is possible that collagen-binding cells may change their
      phenotypic traits. Although the glucose-derived product methylglyoxal (MGO) has
      been detected in periodontal lesions, the precise effect of collagen glycation on
      gingival connective tissue biology is not fully understood. The present study
      evaluates whether collagen glycation by MGO may affect phenotypic properties and
      remodeling capacity of human gingival fibroblasts (HGFs). METHODS: Primary
      cultures of HGFs were grown on Type I collagen matrices previously treated with
      MGO. Cell cultures were tested for cell viability, apoptosis, alpha-smooth muscle
      actin (SMA), fibronectin (FN) production, and collagen remodeling. Mechanical
      properties and morphology of MGO-treated collagen gels were evaluated using
      rheometry and atomic force microscopy. Statistical analysis was performed by
      Kruskal-Wallis and Mann-Whitney U tests. RESULTS: MGO-treated collagen did not
      affect cell viability or apoptosis. In addition, MGO did not induce significant
      changes in morphology or mechanical properties of the collagen matrix. However,
      MGO-treated collagen stimulated an increase in the myofibroblast marker alpha
      SMA, production and assembly of FN, and contraction of collagen matrices.
      Moreover, use of a triple-helical peptide that reconstitutes the collagen-binding
      domain for integrins GFOGER reverted the assembly of FN induced by MGO-treated
      collagen. CONCLUSIONS: The present study shows that collagen glycation by MGO
      stimulates differentiation of myofibroblasts and production and assembly of FN.
      These responses may alter the homeostatic balance and wound-healing response of
      gingival connective tissues affected by diabetes mellitus or aging.

PMID- 28517973
TI  - Periodontal Referral Patterns in Australia: 2000 Versus 2015.
AB  - BACKGROUND: A previous study investigated differences in the severity of
      periodontal disease on referral for specialist care between 1980 and 2000 across
      the United States. The present study finds patients referred in 2000 had greater
      severity of periodontal disease than those referred 20 years ago. METHODS: A
      retrospective analysis of 384 charts was completed from three periodontal
      practices across the east coast of Australia. Two time periods were investigated:
      2000 to 2001 and 2015 to 2016. From these charts, the following data were
      recorded: 1) age; 2) sex; 3) smoking status; 4) number of missing teeth; and 5)
      number of teeth planned for extraction as part of a treatment plan at initial
      examination. Additionally, degree of periodontal severity was determined and
      recorded. The classification system was based on that used by the previous study,
      wherein case Types I to IV defined increasing severity of periodontal disease,
      and Type V defined referrals for needs other than periodontal disease (e.g.,
      crown lengthening and implants). RESULTS: Overall, patients seen in 2015
      presented with a greater percentage of Type IV and Type V cases. Smoking
      prevalence reduced significantly across the three locations between the two time
      periods. No consistent or noteworthy trends were identified with regard to number
      of missing teeth or number of teeth planned for extraction. CONCLUSIONS:
      Consistent with the results of a similar previous study, there appears to be a
      trend for more severe periodontal conditions being referred to periodontists.
      This is concerning given that more severe periodontal conditions tend to be more
      difficult to manage conservatively and reliably.

PMID- 28517974
TI  - Impact of Docosahexaenoic Acid Therapy on Subgingival Plaque Microbiota.
AB  - BACKGROUND: Oral docosahexaenoic acid (DHA) + aspirin therapy has been shown to
      reduce periodontal probing depth (PD) and local inflammatory mediators in
      gingival crevicular fluid (GCF) among patients with untreated chronic periodontal
      disease. Whether DHA + aspirin therapy influences specific bacterial burden in
      this setting is unknown. Thus, the aim of this study is to evaluate the impact of
      DHA with low-dose aspirin therapy on periodontal bacterial profile in patients
      with periodontitis. METHODS: Fifty-five adults with moderate-to-severe
      periodontitis were enrolled in a randomized, 3-month double-masked, placebo
      controlled trial of daily 2 g DHA or placebo capsules enriched with 81 mg
      aspirin; 46 enrollees completed the trial. In addition to clinical measurements
      and GCF sampling, subgingival plaque samples were collected from four posterior
      sites in all participants and analyzed by the checkerboard DNA-DNA hybridization
      technique. Presence of 40 periodontal bacterial species at baseline and 3 months
      was semiquantitatively estimated. RESULTS: Despite broad improvements in clinical
      parameters, total bacteria and individual species counts in dental plaque did not
      differ significantly between baseline and 3 months in either group (P >0.1 for
      all). A modest effect of DHA + aspirin on Porphyromonas gingivalis counts was
      associated with 14% (95% confidence interval: 3% to 35%) of the observed benefit
      of DHA on PD. DHA + aspirin had no significant effect on individual plaque
      bacterial counts in unadjusted models or those adjusted for age, sex, and race (P
      >0.1 for all). CONCLUSIONS: This pilot randomized, controlled trial suggests that
      DHA + aspirin therapy improves periodontitis largely by modulating host
      inflammatory response. Changes in individual species levels in subgingival plaque
      microbiota were not detectable; however, a small portion of the benefit appears
      to stem from changes in P. gingivalis levels in the DHA + aspirin treatment
      group. Whether this change in P. gingivalis levels leads to biofilm alteration
      with reversal of dysbiosis requires further longitudinal and more specific
      investigations.

PMID- 28517975
TI  - Relationship Between Periodontal Screening and Recording Index Scores and Need
      for Periodontal Access Surgery.
AB  - BACKGROUND: The validity of using pretreatment Periodontal Screening and
      Recording (PSR) index sextant scores to estimate periodontal access surgery needs
      is evaluated in patients with chronic periodontitis before and after completion
      of non-surgical periodontal therapy. METHODS: In 110 adults, pretreatment probing
      data identified 486 sextants with PSR scores of 4 and 125 sextants with PSR
      scores of 3. Periodontal access surgery needs for all sextants were determined
      prior to treatment and after completion of non-surgical periodontal therapy for
      213 sextants in 38 patients by two experienced periodontist examiners. RESULTS:
      PSR scores of 4 identified untreated sextants with periodontal access surgery
      needs significantly better than PSR scores of 3 (odds ratio = 27.8; P <0.001) in
      multilevel, mixed-effects, logistic regression modeling analysis. However, only
      37.6% of sextants with both pretreatment PSR scores of 4 and a pretreatment
      periodontal access surgery need continued to have surgical access needs after
      completion of non-surgical periodontal therapy. A higher percentage of sextants
      with PSR scores of 4 or 3 revealed periodontal access surgical needs when Class
      II or III furcation involvements and/or Grade II or III tooth mobility were also
      detected in the sextant than when these parameters were not detected.
      CONCLUSIONS: Pretreatment PSR index scores of 4 were a strong indicator of
      periodontal access surgery needs in untreated dentition sextants but markedly
      overestimated surgical access needs remaining after completion of non-surgical
      periodontal therapy. These findings raise questions about the usefulness of
      pretreatment PSR evaluations for estimating potential periodontal access surgery
      needs in patients to be initially treated with non-surgical periodontal therapy.

PMID- 28517977
TI  - Injectable chelate-setting hydroxyapatite cement prepared by using chitosan
      solution: Fabrication, material properties, biocompatibility, and
      osteoconductivity.
AB  - An injectable chelate-setting hydroxyapatite cement (IP6-HAp), formed by chelate
      bonding capability of inositol phosphate (IP6), was developed. The effects of
      ball-milling duration of starting HAp powder and IP6 concentration on the
      material properties such as injectability and mechanical strength of the cement
      were examined. The cement powder was prepared by ball-milling the as-synthesized
      HAp powder for 5 min using ZrO2 beads with a diameter of 10 mm, followed by
      another 60 min with ZrO2 beads with a diameter of 2 mm, and thereafter surface
      modified with 5000 ppm of IP6 solution. Injectable cement was then fabricated
      with this HAp powder and 2.5 mass% chitosan as a mixing solution, with a setting
      time of 36.3 +/- 4.7 min and a compressive strength of 19.0 +/- 2.1 MPa. The IP6
      HAp cements prepared with chitosan showed favorable biocompatibility in vitro
      using an osteoblast cell model, and osteoconductivity in vivo using a pig tibia
      model.

PMID- 28517976
TI  - Fabrication of micropatterns on polypropylene films via plasma pretreatment
      combined with UV-initiated graft polymerization.
AB  - In this study, micropatterns on polypropylene films were fabricated via plasma
      pretreatment and UV-initiated graft polymerization. Firstly, radio-frequency
      plasma, which does not significantly influence bulk attributes of substrates due
      to limited penetration depth, was utilized to activate polypropylene films. Then,
      different sizes of micropatterns of poly(hydroxyethyl methacrylate) (PHEMA) were
      fabricated on the polypropylene films via UV-initiated graft polymerization of
      hydroxyethyl methacrylate by using photo-masks. Scanning electron microscopy,
      atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle (CA)
      were employed to characterize changes of pristine polypropylene films and
      modified ones in surface morphology, roughness, hydrophilicity, free energy and
      the surface chemical composition. All of these confirmed the successful grafting
      of different sizes of PHEMA micropatterns on the polypropylene surface.
      Furthermore, the influence of PHEMA micropatterns on cell proliferation and
      cytotoxicity was evaluated in vitro. Analysis of cell behaviour indicated that
      PHEMA micropatterns of the appropriate size can promote cellular adhesion and
      proliferation, and the PHEMA-micropatterned polypropylene films had good
      biocompatibility. The approach presented here provides an alternative to
      synthesize on the surface of polypropylene films' micropatterns with the aim of
      using them in a diverse array of applications.

PMID- 28517978
TI  - The effect of carbon nanoparticles on biological properties of polyester
      nanocomposites.
AB  - The aim of present study was to determine the hemocompatibility, cellular
      response of endothelial cells and bacterial adhesion to a new polyester
      nanocomposite. The carbon nanoparticle nanocomposite was prepared via in situ
      polymerization of monomers to obtain material of hardness 55 Sh D similar to
      polyurethanes used in medical applications, for example, in heart-assisting
      devices. The carbon nanoparticle-containing polyester exhibits markedly reduced
      bacterial colonization, as compared to commercially available polyurethanes.
      Further the nanocomposite possesses markedly improved hemocompatibility, as
      determined by flow cytometry, and robust endothelialization. Possible
      explanations for these beneficial properties include surface nanoroughness of
      carbon nanoparticle-containing nanocomposites and presence of fatty acid
      sequences within polymer structure.

PMID- 28517979
TI  - Cell-type deconvolution in epigenome-wide association studies: a review and
      recommendations.
AB  - A major challenge faced by epigenome-wide association studies (EWAS) is cell-type
      heterogeneity. As many EWAS have already demonstrated, adjusting for changes in
      cell-type composition can be critical when analyzing and interpreting findings
      from such studies. Because of their importance, a great number of different
      statistical algorithms, which adjust for cell-type composition, have been
      proposed. Some of the methods are 'reference based' in that they require a priori
      defined reference DNA methylation profiles of cell types that are present in the
      tissue of interest, while other algorithms are 'reference free.' At present,
      however, it is unclear how best to adjust for cell-type heterogeneity, as this
      may also largely depend on the type of tissue and phenotype being considered.
      Here, we provide a critical review of the major existing algorithms for
      correcting cell-type composition in the context of Illumina Infinium Methylation
      Beadarrays, with the aim of providing useful recommendations to the EWAS
      community.

PMID- 28517980
TI  - Identification of prognostic and subtype-specific potential miRNAs in thymoma.
AB  - AIM: We performed a study to identify the role of microRNA in thymoma. PATIENTS &
      METHODS: One hundred twenty-three thymoma patients with clinical information and
      miRNA expression data from The Cancer Genome Atlas were included in the study.
      Comprehensive bioinformatics analysis was integrated in our analysis. RESULTS &
      CONCLUSION: Seven miRNAs were found to be associated with overall survival (p <
      0.001). Another four miRNAs were found to be associated with disease-free
      survival (p < 0.001). Type C thymoma can be distinguished from nontype C thymoma
      by miRNAs. Interestingly, seven miRNAs showed both prognostic and subtype
      specific potential. Our findings suggest that miRNAs can be used for prognostic
      prediction and subtype stratification.

PMID- 28517981
TI  - A systematic review of studies of DNA methylation in the context of a weight loss
      intervention.
AB  - AIM: Obesity results from the interaction of genetic and environmental factors,
      which may involve epigenetic mechanisms such as DNA methylation (DNAm). MATERIALS
      & METHODS: We have followed the PRISMA protocol to select studies that analyzed
      DNAm at baseline and end point of a weight loss intervention using either
      candidate-locus or genome-wide approaches. RESULTS: Six genes displayed weight
      loss associated DNAm across four out of nine genome-wide studies. Weight loss is
      associated with significant but small changes in DNAm across the genome, and
      weight loss outcome is associated with individual differences in baseline DNAm at
      several genomic locations. CONCLUSION: The identified weight loss associated DNAm
      markers, especially those showing reproducibility across different studies,
      warrant validation by further studies with robust design and adequate power.

PMID- 28517982
TI  - Data Sharing and the Idea of Ownership.
AB  - Ideas about ownership are sometimes used in discussions of data sharing in
      personalised medicine. Personal health data are thought by many to be 'theirs'.
      Paradoxically, personalised medicine (at least in the context of genomics) relies
      on the aggregation of private data into a dataset that is held as a form of
      knowledge commons. When the notions of private and common property that lie
      behind this discourse are made explicit we can use thinking about the
      justifications and jurisprudence of property both to clarify the persuasiveness
      and limits of such claims, and also how they differ from other principles that
      are at stake in the interplay between individual and collective goods in the
      delivery of personalised medicine. This shows that ownership might more plausibly
      lie with health professionals than patients. In a socialised medicine system,
      such as the NHS, such professionals are agents of the state and ownership would
      lie with the commons rather than any individual. Common rather than private
      ownership of genomic information may be more appropriate.

PMID- 28517984
TI  - Personalised Medicine Approaches to Screening and Prevention.
AB  - One of the promised benefits of 'personalised' medicine is that it will have a
      positive impact on disease screening and prevention, by enabling more person
      specific estimates of risk, and hence more personalised strategies for screening
      and risk reduction. This article summarises some of the areas in which these
      approaches are already being implemented, but also outlines some of the potential
      difficulties and limitations - and challenges the assumption that 'personalised'
      approaches are necessarily superior for prevention and screening.

PMID- 28517983
TI  - Personalised Medicine and the Economy of Biotechnological Promise.
AB  - Rather than seek to distinguish hype from legitimate promise, it may be more
      helpful to think about personalised medicine as embodying a promissory economy
      which serves both to mobilize resources for research and - partly at least - to
      determine the ends to which that research is directed. Personalised medicine is a
      development of the larger promissory economy of medical biotechnology. As such,
      it systematically conflates public benefit with the pursuit of commercial and
      especially pharmaceutical interests. Consequently, research and development in
      personalised medicine tends to favour the production of expensive new treatments
      over unprofitable forms of prevention or more effective use of older therapies. A
      rebalancing of research priorities is needed to favour the pursuit of public
      benefit, even when it does not deliver private profits. This will in turn require
      sustained reflection, self-criticism and often self-denial on the part of public
      research funders and the scientists they support.

PMID- 28517985
TI  - Personalised Medicine: The Promise, the Hype and the Pitfalls.
AB  - In engaging critically with personalised medicine and mapping pitfalls which mark
      its progress this project aims to stimulate conversations which deal
      intelligently with controversies for the sake of consensus. We aim to ask the
      ethical questions which will lead to the improvement of healthcare and we take an
      open-minded approach to finding answers to them over time. What is or should be
      meant by 'personalised medicine' is a major theme of this issue. It is a debate
      bound up with question of both values in the sense of ethical reflection and
      value in the sense of economic return. This editorial discusses and interrelates
      the articles of the issue under four headings: the promise and the hype of
      personalised medicine; the human person and the communication of risk; data
      sharing and participation; value, equity and power. A key intention throughout is
      to provoke discourse and debate, to identify aspirations which are more grounded
      in myth or hype than reality and to challenge them; and to identify focussed,
      practical questions which need further examination.

PMID- 28517987
TI  - The Human Dimension: Putting the Person into Personalised Medicine.
AB  - Technological advances enabling us to personalise medical interventions at the
      biological level must be matched by parallel advances in how we support the
      informed choices essential to patient and public participation. We cannot take
      participation for granted. To be truly personalised, medicine must take account
      of the perceptions and capabilities that shape participation. To do this, we need
      a better understanding of how people perceive personalised medicine and how they
      judge its value and risks. To realise the promise of 4P medicine we need to
      personalise at the psychosocial as well as biological dimension, putting the
      person into personalised medicine.

PMID- 28517986
TI  - From Rosalind Franklin to Barack Obama: Data Sharing Challenges and Solutions in
      Genomics and Personalised Medicine.
AB  - The collection, storage and use of genomic and clinical data from patients and
      healthy individuals is a key component of personalised medicine enterprises such
      as the Precision Medicine Initiative, the Cancer Moonshot and the 100,000 Genomes
      Project. In order to maximise the value of this data, it is important to embed a
      culture within the scientific, medical and patient communities that supports the
      appropriate sharing of genomic and clinical information. However, this aspiration
      raises a number of ethical, legal and regulatory challenges that need to be
      addressed. The Global Alliance for Genomics and Health, a worldwide coalition of
      researchers, healthcare professionals, patients and industry partners, is
      developing innovative solutions to support the responsible and effective sharing
      of genomic and clinical data. This article identifies the challenges that a data
      sharing culture poses and highlights a series of practical solutions that will
      benefit patients, researchers and society.

PMID- 28517990
TI  - Risk and Benefit in Personalised Medicine: An End User View.
AB  - Personalised, or stratified, medicine is creating opportunities for the
      development of targeted therapies for many hitherto unmet clinical needs. For
      patients and families this is a cause for optimism. But it is unlikely that these
      novel therapies will provide complete cures. Rather they will address some but
      not all symptoms of a condition. In such circumstances, early engagement with
      patients and families will ensure that developments are targeted at those aspects
      of a condition which really matter, not just those that are easy to count. This
      will make the development process more efficient, and improve the likelihood that
      patients will be able to access therapies if the development process is
      successful.

PMID- 28517988
TI  - The Promise and the Hype of 'Personalised Medicine'.
AB  - Personalised medicine is widely considered as the way of the future for medicine.
      However, progress in cancer, with a few outstanding exceptions, has fallen below
      expectations because of the challenges of tumour heterogeneity and clonal
      evolution. In both benign and malignant disease, diseases caused by single
      genetic alterations are more amenable to precision medicine approaches. However,
      most common diseases are caused by a complex interplay of multiple genetic and
      environmental factors making personalised medicine far more challenging. The
      current optimism for personalised medicine is distorting clinical consultations,
      resource allocation and research funding prioritisation. A research active
      clinician must act both as an agent of change and development, and as a
      communicator of realism. Thus personalised medicine that includes a sober
      appreciation of what genomics can achieve, together with continued focus on the
      individual as a person not just as a genome, will contribute to further
      improvements in health and healthcare.

PMID- 28517989
TI  - Economics of Cancer Medicines: For Whose Benefit?
AB  - Although new cancer drugs are continually getting approved and used, the value
      that these drugs add is very debatable. Because of the skyrocketing cost of the
      new drugs, each new approval represents a multibillion market. However, unlike
      other branches of economics, cancer drugs are intricately associated with socio
      political issues, emotional overlay, public pressure, industry manipulation and
      propaganda. In this article, we review the value added by new cancer drugs and
      examine the socio-political agenda around them with highlights on the increasing
      gulf between high-income and low-middle income countries regarding the
      affordability to these drugs. Finally, we also suggest a way forward to address
      this highly complex issue.

PMID- 28517991
TI  - Self-Knowledge and Risk in Stratified Medicine.
AB  - This article considers why and how self-knowledge is important to communication
      about risk and behaviour change by arguing for four claims. First, it is doubtful
      that genetic knowledge should properly be called 'self-knowledge' when its
      ordinary effects on self-motivation and behaviour change seem so slight. Second,
      temptations towards a reductionist, fatalist, construal of persons' futures
      through a 'molecular optic' should be resisted. Third, any plausible effort to
      change people's behaviour must engage with cultural self-knowledge, values and
      beliefs, catalysed by the communication of genetic risk. For example, while a
      Judaeo-Christian notion of self-knowledge is distinctively theological, people's
      self-knowledge is plural in its insight and sources. Fourth, self-knowledge is
      found in compassionate, if tense, communion which yields freedom from determinism
      even amidst suffering. Stratified medicine thus offers a newly precise kind of
      humanising health care through societal solidarity with the riskiest. However,
      stratification may also mean that molecularly unstratified, 'B' patients'
      experience involves accentuated suffering and disappointment, a concern requiring
      further research.

PMID- 28517992
TI  - Equity and Value in 'Precision Medicine'.
AB  - Precision medicine carries huge potential in the treatment of many diseases,
      particularly those with high-penetrance monogenic underpinnings. However,
      precision medicine through genomic technologies also has ethical implications. We
      will define allocative, personal, and technical value ('triple value') in
      healthcare and how this relates to equity. Equity is here taken to be implicit in
      the concept of triple value in countries that have publicly funded healthcare
      systems. It will be argued that precision medicine risks concentrating resources
      to those that already experience greater access to healthcare and power in
      society, nationally as well as globally. Healthcare payers, clinicians, and
      patients must all be involved in optimising the potential of precision medicine,
      without reducing equity. Throughout, the discussion will refer to the NHS
      RightCare Programme, which is a national initiative aiming to improve value and
      equity in the context of NHS England.

PMID- 28517993
TI  - Your DNA, Your Say.
AB  - Genomic and medical data sharing is pivotal if the promise of genomic medicine is
      to be fully realised. Social scientists working in the genomics arena ask the
      public 'how is the technology working for you?' Empirical studies on attitudes,
      values and beliefs are incredibly valuable; they offer a voice from those who
      are, or will be, directly affected. This is paramount if personalised medicine is
      to be truly personal. An International attitude study, Your DNA, Your Say, uses
      film to provide background information and an online survey to gather public
      views on donating one's own personal DNA and medical data for use by others. In
      this paper the rationale to the project is introduced together with an overview
      of the survey and film design. The project has been translated into multiple
      languages and the results will be used in policy for the Global Alliance for
      Genomics and Health.

PMID- 28517994
TI  - Dr. Lynne Anne Fulton (1949-2017).

PMID- 28517995
TI  - "Moments".

PMID- 28517996
TI  - Prevalence of potential smoking-related conditions among tobacco users in the
      emergency department and their perception that their visit may be smoking-related
      - ERRATUM.

PMID- 28517998
TI  - To Publish, Publish, and Publish Again.

PMID- 28517999
TI  - Venous Gas Emboli and Ambulation at 4.3 psia.
AB  - INTRODUCTION: Ambulation during extravehicular activity on Mars may increase the
      risk of decompression sickness through enhanced bubble formation in the lower
      body. HYPOTHESES: walking effort (ambulation) before an exercise-enhanced
      denitrogenation (prebreathe) protocol at 14.7 psia does not increase the
      incidence of venous gas emboli (VGE) at 4.3 psia, but does increase incidence if
      performed after tissues become supersaturated with nitrogen at 4.3 psia. METHODS:
      VGE results from 45 control subjects who performed exercise prebreathe without
      ambulation before or during a 4-h exposure to 4.3 psia were compared to 21
      subjects who performed the same prebreathe but ambulated before and during the
      hypobaric exposure (Group I) and to 41 subjects who only ambulated before the
      hypobaric exposure (Group II). Monitoring for VGE in the pulmonary artery was for
      4 min at about 12-min intervals using precordial Doppler ultrasound (2.5 mHz).
      Detected VGE were assigned a categorical grade from I to IV. The detection of
      Grade III or IV was classified as "high VGE grade." RESULTS: The incidence of
      high VGE grade for Group I (57%) was greater than the control (17%) and Group II
      (15%). The incidence of pain-only decompression sickness was greater for Group I
      (20%) than the control (0%) and Group II (5%). CONCLUSIONS: High-grade VGE are
      increased by mild ambulation conducted under a supersaturated state (Group I vs.
      II); however, no increase was observed with mild ambulation during the saturated
      state alone (control vs. Group II).Conkin J, Pollock NW, Natoli MJ, Martina SD,
      Wessell JH III, Gernhardt ML. Venous gas emboli and ambulation at 4.3 psia.
      Aerosp Med Hum Perform. 2017; 88(4):370-376.

PMID- 28518000
TI  - Comparison of Simulated Microgravity and Hydrostatic Pressure for Chondrogenesis
      of hASC.
AB  - BACKGROUND: Cartilage tissue engineering is a growing field due to the lack of
      regenerative capacity of native tissue. The use of bioreactors for cartilage
      tissue engineering is common, but the results are controversial. Some studies
      suggest that microgravity bioreactors are ideal for chondrogenesis, while others
      show that mimicking hydrostatic pressure is crucial for cartilage formation. A
      parallel study comparing the effects of loading and unloading on chondrogenesis
      has not been performed. METHODS: The goal of this study was to evaluate
      chondrogenesis of human adipose-derived stem cells (hASC) under two different
      mechanical stimuli relative to static culture: microgravity and cyclic
      hydrostatic pressure (CHP). Pellets of hASC were cultured for 14 d under
      simulated microgravity using a rotating wall vessel bioreactor or under CHP (7.5
      MPa, 1 Hz, 4 h . d-1) using a hydrostatic pressure vessel. RESULTS: We found that
      CHP increased mRNA expression of Aggrecan, Sox9, and Collagen II, caused a
      threefold increase in sulfated glycosaminoglycan production, and resulted in
      stronger vimentin staining intensity and organization relative to microgravity.
      In addition, Wnt-signaling patterns were altered in a manner that suggests that
      simulated microgravity decreases chondrogenic differentiation when compared to
      CHP. DISCUSSION: Our goal was to compare chondrogenic differentiation of hASC
      using a microgravity bioreactor and a hydrostatic pressure vessel, two commonly
      used bioreactors in cartilage tissue engineering. Our results indicate that CHP
      promotes hASC chondrogenesis and that microgravity may inhibit hASC
      chondrogenesis. Our findings further suggest that cartilage formation and
      regeneration might be compromised in space due to the lack of mechanical
      loading.Mellor LF, Steward AJ, Nordberg RC, Taylor MA, Loboa EG. Comparison of
      simulated microgravity and hydrostatic pressure for chondrogenesis of hASC.
      Aerosp Med Hum Perform. 2017; 88(4):377-384.

PMID- 28518001
TI  - Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in
      Swine.
AB  - INTRODUCTION: Disabled submarine (DISSUB) survivors may face elevated CO2 levels
      and inert gas saturation, putting them at risk for CO2 toxicity and decompression
      sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental
      DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are
      unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is
      incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB
      rescue to study the effect of propranolol on DCS incidence and mortality with and
      without an OPB. METHODS: In Experiment 1, male Yorkshire Swine (70 kg) were
      pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg . kg-1 (IV) was administered
      at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS
      type, onset time, and mortality. Experimental animals (N = 21; 69 +/- 4.1 kg),
      PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 +/- 2.8 kg) with the same dive
      profile, except for a 45 min OPB prior to decompression. In Experiment 2, the
      same methodology was used with the following changes: swine pressurized to 2.8
      ATA for 28 h; experimental group (N = 25; 67 +/- 3.3 kg), PROP0.5 bis,
      propranolol 0.5 mg . kg-1 bis (twice) (IV) was administered at 22 h and 26 h.
      Control animals (N = 25; 67 +/- 3.9 kg) received normal saline. RESULTS: OPB
      reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis
      had increased mortality compared to CONTROL (60-% vs. 4%). DISCUSSION:
      Administration of beta blockers prior to saturation decompression appears to
      increase DCS and worsen mortality in a swine model; however, their effects in
      bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA.
      Propranolol effects on decompression sickness in a simulated DISSUB rescue in
      swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

PMID- 28518002
TI  - Cognitive Evaluation of Israeli Air Force Pilot Cadets.
AB  - OBJECTIVE: In aviation psychology, there is a constant need for the cognitive
      evaluation of pilots as part of operational fitness and safety criteria. METHODS:
      A cross-sectional study with comparison between the performance of Israeli Air
      Force pilot cadets (N = 318) and U.S. Air Force pilot training candidates (N =
      512) as assessed by a cognitive battery was undertaken. The data of the
      comparison group was collected from Callister, King, and Retzlaff, as published
      in 1996. RESULTS: In general, the means in the three components composing the
      battery-speed, accuracy, and throughput variables-indicated that the Israeli Air
      Force pilot cadets' scores were higher than those of the U.S. Air Force pilot
      candidates' scores in 50 of 53 variables. Nonsignificant differences were found
      in Accuracy of shifting attention-arrow color (SATAC), pathfinder-combined (PFC),
      and pathfinder-letter (PFL). CONCLUSIONS: The difference in performance between
      the two groups may be due to differences in population characteristics. However,
      these results need to be considered cautiously, as the groups were sampled at a
      sizeable time gap (1996 for the U.S. Air Force vs. 2013 for the Israeli Air
      Force), with each time period characterized by different cultural and
      technological influences.Gordon S, Goren C, Carmon E, Shelef L. Cognitive
      evaluation of Israeli Air Force pilot cadets. Aerosp Med Hum Perform. 2017;
      88(4):392-398.

PMID- 28518003
TI  - Caffeine Consumption Among Naval Aviation Candidates.
AB  - INTRODUCTION: Education frequently dictates students need to study for prolonged
      periods of time to adequately prepare for examinations. This is especially true
      with aviation preflight indoctrination (API) candidates who have to assimilate
      large volumes of information in a limited amount of time during API training. The
      purpose of this study was to assess caffeine consumption patterns (frequency,
      type, and volume) among naval aviation candidates attending API to determine the
      most frequently consumed caffeinated beverage and to examine if the consumption
      of a nonenergy drink caffeinated beverage was related to energy drink
      consumption. METHODS: Data were collected by means of an anonymous 44-item survey
      administered and completed by 302 students enrolled in API at Naval Air Station
      Pensacola, FL. RESULTS: Results indicated the most frequently consumed
      caffeinated beverage consumed by API students was coffee (86.4%), with daily
      coffee consumption being approximately 28% and the most frequent pattern of
      consumption being 2 cups per day (85%). The least frequently consumed caffeinated
      beverages reported were energy drinks (52%) and energy shots (29.1%). The present
      study also found that the consumption patterns (weekly and daily) of caffeinated
      beverages (coffee and cola) were positively correlated to energy drink
      consumption patterns. DISCUSSION: Naval aviation candidates' consumption of
      caffeinated beverages is comparable to other college and high school cohorts.
      This study found that coffee and colas were the beverages of choice, with energy
      drinks and energy shots being the least frequently reported caffeinated beverages
      used. Additionally, a relationship between the consumption of caffeinated
      beverages and energy drinks was identified.Sather TE, Williams RD, Delorey DR,
      Woolsey CL. Caffeine consumption among naval aviation candidates. Aerosp Med Hum
      Perform. 2017; 88(4):399-405.

PMID- 28518004
TI  - Middle Ear Barotrauma in Student Pilots.
AB  - INTRODUCTION: The present study reports the clinical features of middle ear
      barotrauma in student pilots in the Republic of Korea Air Force. METHODS: The
      authors reviewed medical records of student pilots with barotrauma. The grade of
      barotrauma was assigned using Teed's classification. This study included nasal
      symptoms, endoscopic findings of the nasal cavity, and clinical course (duration,
      recurrence). The relationship between middle ear barotrauma and the nasal airway
      was also evaluated. RESULTS: There were 57 cases in 51 pilots included. There
      were 49 cases (86.0%) that showed unilateral disease and 4 subjects experienced
      relapse. Two subjects (3.9%) had chronic rhinosinusitis and four subjects (7.8%)
      had allergic rhinitis. Ear fullness was reported in all cases, while hearing loss
      and persistent ear pain were reported in 3 cases (5.3%) and 19 cases (33.3%),
      respectively. Stuffy nose (26 cases, 45.6%) and rhinorrhea (24 cases, 42.1%) were
      relatively common. Most cases were Grade 0 (23 cases, 40.3%) or Grade III (27
      cases, 47.4%) according to Teed's classification. Septal deviation was observed
      in 12 cases (21.0%), while turbinate hypertrophy was seen in 53 cases (93.0%) and
      increased nasal discharge in 33 cases (57.9%). The grade of barotrauma varied
      significantly according to the severity of turbinate hypertrophy and nasal
      discharge. The mean duration of disease was 6.8 d. DISCUSSION: Nasal symptoms and
      endoscopic findings showed some association with the grade and duration of
      barotrauma. Most cases resolved within a week; however, barotrauma showed
      persistence or relapse in some cases.Sohn JH, Cho KR. Middle ear barotrauma in
      student pilots. Aerosp Med Hum Perform. 2017; 88(4):406-412.

PMID- 28518005
TI  - Safety Considerations for Medical Staff and Patients Who Fly Over Water in a
      Helicopter for Work or Recreation.
AB  - BACKGROUND: Around 25% of people involved in a helicopter accident in water do
      not survive. From time to time, physicians and their medical staff are required
      to fly over water in a helicopter to attend one or more seriously ill patients.
      Many will have had little or no experience of the issues involved if the
      helicopter has an accident in the water. Also as Family Practitioners,
      Aeromedical Examiners, and Flight Surgeons, they are asked to provide advice to
      patients, travel agents, and airline booking agents about whether an overwater
      helicopter flight is advisable or not. METHOD: From 50 yr of helicopter accident
      evidence in the scientific literature, government agency reports, and statistics
      from the military safety centers and the offshore oil industry, the critical
      hazards involved and risks to medical staff and their patients have been
      identified. RESULTS: Patients most at risk are those who suffer from
      cardiovascular or respiratory disease, have physical disabilities, have a very
      large body size, and anyone who is a non-swimmer. Medical staff are at risk if
      they are not familiar with the procedure for escape from a flooded inverted cabin
      and difficulties after escape from the fuselage with life jackets, life rafts,
      and sometimes the necessity to swim ashore. CONCLUSIONS: With 50 yr of hindsight,
      many of the deaths were preventable, and many lives can be saved if a series of
      very simple mental and physical preventive actions are taken by anyone stepping
      on to a helicopter that flies over water.Brooks CJ, MacDonald CV. Safety
      considerations for medical staff and patients who fly over water in a helicopter
      for work or recreation. Aerosp Med Hum Perform. 2017; 88(4):413-417.

PMID- 28518007
TI  - Patient-Centric Side Effect Risk Assessment for Medications Used During
      Aeromedical Evacuations.
AB  - BACKGROUND: The U.S. Air Force performs more than 6000 aeromedical transport
      flights annually, both internationally and domestically. Many of these flights
      include patients requiring pain relief medications. The risk of side effects from
      such medications administered at altitude is unknown, but understanding these
      risks is vital when selecting the safest pain management strategies to achieve
      optimal postflight outcomes. METHODS: Using an evidence-based medication side
      effect risk assessment model, we compared our patient-centric approach to an
      aircrew-centric approach using medications approved for use in U.S. Navy aircrew.
      We then determined the patient-centric side effect risk of medications commonly
      used during Air Force aeromedical evacuation (AE). RESULTS: The patient-centric
      approach to medication side effect risk assessment demonstrates that the majority
      of medications currently approved for use during AE have an acceptable side
      effect risk for the patient (18/22, 82%). Four approved drugs displayed
      significantly elevated patient risk, with risk scores between 2.0- and 3.2-fold
      greater than the statistically determined upper allowable ("acceptable") limit
      and between 1.2- and 2.0-fold above the upper control ("tolerable") limit.
      DISCUSSION: Our results suggest that pain management strategies during AE should
      be tailored individually to minimize the risk associated with pain medications
      administered en route.Huntsberger SA, Butler WP, Chapleau RR. Patient-centric
      side effect risk assessment for medications used during aeromedical evacuations.
      Aerosp Med Hum Perform. 2017; 88(4):423-426.

PMID- 28518006
TI  - Cooling Effects of Wearer-Controlled Vaporization for Extravehicular Activity.
AB  - INTRODUCTION: The extravehicular activity suit currently used by the United
      States in space includes a liquid cooling and ventilation garment (LCVG) that
      controls thermal conditions. Previously, we demonstrated that self-perspiration
      for evaporative cooling (SPEC) garment effectively lowers skin temperature
      without raising humidity in the garment. However, the cooling effect is delayed
      until a sufficient dose of water permeates and evaporates. In the present study,
      we hypothesized that wearer-controlled vaporization improves the cooling effect.
      METHODS: Six healthy subjects rode a cycle ergometer under loads of 30, 60, 90,
      and 120 W for durations of 3 min each. Skin temperature and humidity on the back
      were measured continuously. Subjects wore and tested three garments: 1) a spandex
      garment without any cooling device (Normal); 2) a simulated LCVG (s-LCVG) or
      spandex garment knitted with a vinyl tube for flowing and permeating water; and
      3) a garment that allowed wearer-controlled vaporization (SPEC-W). RESULTS: The
      use of s-LCVG reduced skin temperature by 1.57 +/- 0.14 degrees C during 12 min
      of cooling. Wearer-controlled vaporization of the SPEC-W effectively and
      significantly lowered skin temperature from the start to the end of cycle
      exercise. This decrease was significantly larger than that achieved using s-LCVG.
      Humidity in the SPEC-W was significantly lower than that in s-LCVG. DISCUSSION:
      This preliminary study suggests that SPEC-W is effective in lowering skin
      temperature without raising humidity in the garment. The authors think it would
      be useful in improving the design of a cooling system for extravehicular
      activity.Tanaka K, Nagao D, Okada K, Nakamura K. Cooling effects of wearer
      controlled vaporization for extravehicular activity. Aerosp Med Hum Perform.
      2017; 88(4):418-422.

PMID- 28518008
TI  - Latent Presentation of Decompression Sickness After Altitude Chamber Training in
      an Active Duty Flier.
AB  - BACKGROUND: Decompression sickness (DCS) is a potential danger and risk for both
      divers and aircrew alike. DCS is also a potential side effect of altitude
      (hypobaric) chamber training as well and can present long after training occurs.
      Literature review shows that altitude chamber induced DCS has approximately a
      0.25% incidence. CASE REPORT: A 32-yr-old, active duty military member developed
      symptoms of DCS 3 h after his hypobaric chamber training. Unfortunately, he did
      not seek treatment for DCS until 48 h after the exposure. His initial treatment
      included ground level oxygen therapy for 30 min at 12 L of oxygen per minute
      using a nonrebreathing mask. He achieved complete symptom resolution and was
      returned to duty. However, 12 d after his initial Flight Medicine evaluation, the
      patient returned complaining of a right temporal headache, multijoint pains, and
      fatigue. He was treated in the hyperbaric chamber and had complete resolution of
      symptoms. He was returned to flying status and 5 mo later denied any return of
      symptoms. DISCUSSION: Hypobaric chamber familiarity training is a requirement for
      all military aircrew personnel to allow them assess their ability to identify
      symptoms of hypoxia. This training method is not only costly to maintain, but it
      also places aircrew and chamber technicians at risk for potential long-term side
      effects from failed recompression treatment of DCS. We are presenting a case of
      recurrent DCS symptoms 12 d after initial ground level oxygen therapy.Gentry J,
      Rango J, Zhang J, Biedermann S. Latent presentation of decompression sickness
      after altitude chamber training in an active duty flier. Aerosp Med Hum Perform.
      2017; 88(4):427-430.

PMID- 28518009
TI  - Aeromedical Evacuation Using Extra Corporeal Life Support After Resuscitated
      Cardiac Arrest.
AB  - BACKGROUND: Extra corporeal life support (ECLS) is presently first line therapy
      for refractory cardiogenic shock. Mobile circulatory support teams implant ECLS
      or extra corporeal membrane oxygenation (ECMO) in patients in the hospital
      without circulatory support. These patients are then transported to specialized
      centers. Here we report a case of sending a mobile circulatory support team
      abroad, followed by air ambulance evacuation, which, to our knowledge, has never
      been used as part of medical assistance abroad. CASE REPORT: In June, during a
      holiday in Turkey, a 56-yr-old woman complained about chest pain. She had a
      cardiac arrest and was resuscitated with no no-flow time in the local hospital.
      ECG showed ST segment elevation. Medic'Air International medical assistance
      (Paris, France) contacted the hospital, which was not equipped with
      coronarography or cardiac ultrasound and the local treating doctor refused
      transfer of the patient to another facility. A medical team completed by a
      cardiothoracic surgeon and a perfusionist went from Paris to the patient's
      bedside by air ambulance. They implemented the ECLS and successfully repatriated
      the patient to her home country (Belgium). The patient's condition improved, she
      neurologically improved, and returned home on the 14th day. DISCUSSION: Possible
      indications for ECLS repatriations firstly take into account recognized ECLS
      indications and case-by-case discussions on the evaluation of inadequacy of the
      health facilities and risk-benefit balance. In international medical assistance,
      this case's description is an example of repatriation for patients who previously
      could not be transferred due to high risk of such intervention.Gerard D, Raffin
      H, Lebreton G. Aeromedical evacuation using extra corporeal life support after
      resuscitated cardiac arrest. Aerosp Med Hum Perform. 2017; 88(4):431-433.

PMID- 28518010
TI  - Mechanical Simulators of the Cardiovascular System: An Alternative to Research
      Subjects and Patients.

PMID- 28518012
TI  - You're the Flight Surgeon.
AB  - Milner MR. You're the flight surgeon: an unusual case of pharyngitis. Aerosp Med
      Hum Perform. 2017; 88(4):439-442.

PMID- 28518011
TI  - You're the Flight Surgeon.
AB  - Ensley D. You're the flight surgeon: green laser event. Aerosp Med Hum Perform.
      2017; 88(4):437-439.

PMID- 28518013
TI  - Thomas R. White, M.D., Doolittle Raider Flight Surgeon.

PMID- 28518014
TI  - Erratum.

PMID- 28518015
TI  - This Month in Aerospace Medicine History.

PMID- 28518016
TI  - This Month in Aerospace Medicine History.

PMID- 28518017
TI  - Enterocytozoon bieneusi Microsporidiosis in Stem Cell Transplant Recipients
      Treated with Fumagillin
AB  - Enterocytozoon bieneusi microsporidiosis is an emerging disease in
      immunocompromised patients. We report 2 cases of this disease in allogeneic
      hematopoietic stem cell transplant patients successfully treated with fumagillin.
      Thrombocytopenia occurred but without major adverse events. Modifications of
      immunosuppression could be avoided when E. bieneusi is rapidly identified and
      fumagillin therapy is started promptly.

PMID- 28518018
TI  - Penicillin Resistance of Nonvaccine Type Pneumococcus before and after PCV13
      Introduction, United States.
AB  - Introduction of 13-valent pneumococcal conjugate vaccine in the United States was
      not associated with a significant change in prevalence of penicillin resistance
      in nonvaccine type serotypes because of the variable success of highly resistant
      serotypes. Differences in regional serotype distribution and serotype-specific
      resistance contributed to geographic heterogeneity of penicillin resistance.

PMID- 28518019
TI  - Ebola Virus Imported from Guinea to Senegal, 2014.
AB  - In March 2014, the World Health Organization declared an outbreak of Ebola virus
      disease in Guinea. In August 2014, a case caused by virus imported from Guinea
      occurred in Senegal, most likely resulting from nonsecure funerals and travel.
      Preparedness and surveillance in Senegal probably prevented secondary cases.

PMID- 28518021
TI  - Endemic Hantavirus in Field Voles, Northern England.
AB  - We report a PCR survey of hantavirus infection in an extensive field vole
      (Microtus agrestis) population present in the Kielder Forest, northern England. A
      Tatenale virus-like lineage was frequently detected (~17% prevalence) in liver
      tissue. Lineages genetically similar to Tatenale virus are likely to be endemic
      in northern England.

PMID- 28518020
TI  - Outbreaks of Tilapia Lake Virus Infection, Thailand, 2015-2016.
AB  - During 2015-2016, several outbreaks of tilapia lake virus infection occurred
      among tilapia in Thailand. Phylogenetic analysis showed that the virus from
      Thailand grouped with a tilapia virus (family Orthomyxoviridae) from Israel. This
      emerging virus is a threat to tilapia aquaculture in Asia and worldwide.

PMID- 28518023
TI  - Zika Virus-Associated Cognitive Impairment in Adolescent, 2016.
AB  - Incidence of neurologic manifestations associated with Zika virus infection has
      been increasing. In 2016, neuropsychological and cognitive changes developed in
      an adolescent after travel to a Zika virus-endemic area. Single-photon emission
      computed tomography and neuropsychological testing raised the possibility that
      Zika virus infection may lead to neuropsychiatric and cognitive symptoms.

PMID- 28518022
TI  - High Frequency of Mayaro Virus IgM among Febrile Patients, Central Brazil.
AB  - Mayaro virus (MAYV), an Aedes mosquito-borne alphavirus, is endemic to Brazil and
      other South America countries. We investigated dengue- and chikungunya-negative
      febrile patients visiting rural areas near Goiania, Goias, and found a high
      proportion (55%) of MAYV IgM. Our findings suggest the presence of highly endemic
      foci of MAYV in central Brazil.

PMID- 28518024
TI  - Tick-Borne Encephalitis Virus in Ticks and Roe Deer, the Netherlands.
AB  - We report the presence of tick-borne encephalitis virus (TBEV) in the
      Netherlands. Serologic screening of roe deer found TBEV-neutralizing antibodies
      with a seroprevalence of 2%, and TBEV RNA was detected in 2 ticks from the same
      location. Enhanced surveillance and awareness among medical professionals has led
      to the identification of autochthonous cases.

PMID- 28518025
TI  - Rise in Group W Meningococcal Carriage in University Students, United Kingdom.
AB  - MenACWY conjugate vaccination was recently introduced in the United Kingdom for
      adolescents and young adults to reduce disease from infection by Neisseria
      meningitidis group W. We conducted a cross-sectional meningococcal carriage study
      in first-year UK university students. Despite 71% MenACWY vaccine coverage,
      carriage of group W increased substantially.

PMID- 28518026
TI  - Outbreak-Related Disease Burden Associated with Consumption of Unpasteurized
      Cow's Milk and Cheese, United States, 2009-2014.
AB  - The growing popularity of unpasteurized milk in the United States raises public
      health concerns. We estimated outbreak-related illnesses and hospitalizations
      caused by the consumption of cow's milk and cheese contaminated with Shiga toxin
      producing Escherichia coli, Salmonella spp., Listeria monocytogenes, and
      Campylobacter spp. using a model relying on publicly available outbreak data. In
      the United States, outbreaks associated with dairy consumption cause, on average,
      760 illnesses/year and 22 hospitalizations/year, mostly from Salmonella spp. and
      Campylobacter spp. Unpasteurized milk, consumed by only 3.2% of the population,
      and cheese, consumed by only 1.6% of the population, caused 96% of illnesses
      caused by contaminated dairy products. Unpasteurized dairy products thus cause
      840 (95% CrI 611-1,158) times more illnesses and 45 (95% CrI 34-59) times more
      hospitalizations than pasteurized products. As consumption of unpasteurized dairy
      products grows, illnesses will increase steadily; a doubling in the consumption
      of unpasteurized milk or cheese could increase outbreak-related illnesses by 96%.

PMID- 28518027
TI  - Measles Cases during Ebola Outbreak, West Africa, 2013-2106.
AB  - The recent Ebola outbreak in West Africa caused breakdowns in public health
      systems, which might have caused outbreaks of vaccine-preventable diseases. We
      tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra
      Leone, for measles. These patients were negative for Ebola virus. Measles virus
      IgM was detected in 13 (16%) of the patients.

PMID- 28518028
TI  - Brucella neotomae Infection in Humans, Costa Rica.
AB  - Several species of Brucella are known to be zoonotic, but B. neotomae infection
      has been thought to be limited to wood rats. In 2008 and 2011, however, B.
      neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis.
      The nonzoonotic status of B. neotomae should be reassessed.

PMID- 28518029
TI  - Influenza A(H9N2) Virus, Myanmar, 2014-2015.
AB  - Routine surveillance of influenza A virus was conducted in Myanmar during 2014
      2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole
      genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2
      virus of clade 4.2.5 from China.

PMID- 28518030
TI  - Serologic and Molecular Evidence of Vaccinia Virus Circulation among Small
      Mammals from Different Biomes, Brazil.
AB  - Vaccinia virus (VACV) is a zoonotic agent that causes a disease called bovine
      vaccinia, which is detected mainly in milking cattle and humans in close contact
      with these animals. Even though many aspects of VACV infection have been
      described, much is still unknown about its circulation in the environment and its
      natural hosts/reservoirs. To investigate the presence of Orthopoxvirus antibodies
      or VACV DNA, we captured small rodents and marsupials in 3 areas of Minas Gerais
      state, Brazil, and tested their samples in a laboratory. A total of 336 animals
      were tested; positivity ranged from 18.1% to 25.5% in the 3 studied regions
      located in different biomes, including the Atlantic Forest and the Cerrado.
      Analysis of nucleotide sequences indicated co-circulation of VACV groups I and
      II. Our findings reinforce the possible role played by rodents and marsupials in
      VACV maintenance and its transmission chain.

PMID- 28518031
TI  - Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain,
      Japan, 2014.
AB  - During March-July 2014, rotavirus G8P[8] emerged as the predominant cause of
      rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical
      characteristics were similar for infections caused by G8 and non-G8 strains.
      Sequence and phylogenetic analyses suggest the strains were generated by multiple
      reassortment events between DS-1-like P[8] strains and bovine strains from Asia.

PMID- 28518032
TI  - Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.
AB  - In September 2014, a single fatal case of Marburg virus was identified in a
      healthcare worker in Kampala, Uganda. The source of infection was not identified,
      and no secondary cases were identified. We describe the rapid identification,
      laboratory diagnosis, and case investigation of the third Marburg virus outbreak
      in Uganda.

PMID- 28518034
TI  - Relative Risk for Ehrlichiosis and Lyme Disease in an Area Where Vectors for Both
      Are Sympatric, New Jersey, USA.

PMID- 28518033
TI  - Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease
      Prions in Tissues of Clinical and Asymptomatic Patients.
AB  - In the United-Kingdom, ~1 of 2,000 persons could be infected with variant
      Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by
      medical procedures remains a major concern for public health authorities. In this
      study, we used in vitro amplification of prions by protein misfolding cyclic
      amplification (PMCA) to estimate distribution and level of the vCJD agent in 21
      tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person
      with vCJD. PMCA identified major levels of vCJD prions in a range of tissues,
      including liver, salivary gland, kidney, lung, and bone marrow. Bioassays
      confirmed that the quantitative estimate of levels of vCJD prion accumulation
      provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings
      provide critical data for the design of measures to minimize risk for iatrogenic
      transmission of vCJD.

PMID- 28518035
TI  - Angiostrongylus cantonensis Meningitis and Myelitis, Texas, USA.
AB  - Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast
      Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in
      summer 2013 in a child with no history of travel outside of Texas, USA.
      Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and
      warrants increased awareness among healthcare providers.

PMID- 28518036
TI  - Sustainability of High-Level Isolation Capabilities among US Ebola Treatment
      Centers.
AB  - To identify barriers to maintaining and applying capabilities of US high-level
      isolation units (HLIUs) used during the Ebola virus disease outbreak, during 2016
      we surveyed HLIUs. HLIUs identified sustainability challenges and reported the
      highly infectious diseases they would treat. HLIUs expended substantial resources
      in development but must strategize models of sustainability to maintain
      readiness.

PMID- 28518037
TI  - Crimean-Congo Hemorrhagic Fever in Migrant Worker Returning from Oman to India,
      2016.
AB  - In January 2016, a migrant worker who returned home to India after becoming ill
      in Oman was confirmed to have Crimean-Congo hemorrhagic fever (CCHF). Physicians
      should include CCHF in the differential diagnosis for patients with hemorrhagic
      signs and a history of recent travel to any area where CCHF is endemic or
      prevalent.

PMID- 28518038
TI  - Febrile Respiratory Illness Associated with Human Adenovirus Type 55 in South
      Korea Military, 2014-2016
AB  - An outbreak of febrile respiratory illness associated with human adenovirus
      (HAdV) occurred in the South Korea military during the 2014-15 influenza season
      and thereafter. Molecular typing and phylogenetic analysis of patient samples
      identified HAdV type 55 as the causative agent. Emergence of this novel HAdV
      necessitates continued surveillance in military and civilian populations.

PMID- 28518040
TI  - Highly Pathogenic Avian Influenza Virus (H5N8) Clade 2.3.4.4 Infection in
      Migratory Birds, Egypt.
AB  - We isolated highly pathogenic avian influenza virus (H5N8) of clade 2.3.4.4 from
      the common coot (Fulica atra) in Egypt, documenting its introduction into Africa
      through migratory birds. This virus has a close genetic relationship with subtype
      H5N8 viruses circulating in Europe. Enhanced surveillance to detect newly
      emerging viruses is warranted.

PMID- 28518041
TI  - Stockpiling Ventilators for Influenza Pandemics.
AB  - In preparing for influenza pandemics, public health agencies stockpile critical
      medical resources. Determining appropriate quantities and locations for such
      resources can be challenging, given the considerable uncertainty in the timing
      and severity of future pandemics. We introduce a method for optimizing stockpiles
      of mechanical ventilators, which are critical for treating hospitalized influenza
      patients in respiratory failure. As a case study, we consider the US state of
      Texas during mild, moderate, and severe pandemics. Optimal allocations prioritize
      local over central storage, even though the latter can be deployed adaptively, on
      the basis of real-time needs. This prioritization stems from high geographic
      correlations and the slightly lower treatment success assumed for centrally
      stockpiled ventilators. We developed our model and analysis in collaboration with
      academic researchers and a state public health agency and incorporated it into a
      Web-based decision-support tool for pandemic preparedness and response.

PMID- 28518039
TI  - Central Nervous System Brucellosis Granuloma and White Matter Disease in
      Immunocompromised Patient.
AB  - Brucellosis is a multisystem zoonotic disease. We report an unusual case of
      neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia
      who underwent renal transplantation. Magnetic resonance imaging of the brain
      showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive
      for Brucella sp. Granuloma was detected in a brain biopsy specimen.

PMID- 28518042
TI  - Autochthonous Case of Eosinophilic Meningitis Caused by Angiostrongylus
      cantonensis, France, 2016.
AB  - We report a case of a 54-year-old Moroccan woman living in France diagnosed with
      eosinophilic meningitis caused by Angiostrongylus cantonensis. Diagnosis was
      based on clinical symptoms and confirmed by testing of serum and cerebrospinal
      fluid samples. Physicians should consider the risk for A. cantonensis infection
      outside of endemic areas.

PMID- 28518043
TI  - Congenital Malformations of Calves Infected with Shamonda Virus, Southern Japan.
AB  - In 2015 and 2016, we observed 15 malformed calves that were exposed to
      intrauterine infection with Shamonda virus, a Simbu serogroup orthobunyavirus, in
      Japan. Characteristic manifestations were arthrogryposis and gross lesions in the
      central nervous system. Our results indicate that this arbovirus should be
      considered a teratogenic virus in ruminants.

PMID- 28518044
TI  - PCR Detection of Mimivirus.

PMID- 28518045
TI  - High Rates of Neutralizing Antibodies to Toscana and Sandfly Fever Sicilian
      Viruses in Livestock, Kosovo.
AB  - Toscana and sandfly fever Sicilian viruses (TOSV and SFSV, respectively), both
      transmitted by sand flies, are prominent human pathogens in the Old World. Of
      1,086 serum samples collected from cattle and sheep during 2013 in various
      regions of Kosovo (Balkan Peninsula), 4.7% and 53.4% had neutralizing antibodies
      against TOSV and SFSV, respectively.

PMID- 28518047
TI  - Canadian Spine Society Abstracts 2017.

PMID- 28518046
TI  - Epidemiologic Survey of Japanese Encephalitis Virus Infection, Tibet, China,
      2015.
AB  - We investigated Japanese encephalitis virus (JEV) prevalence in high-altitude
      regions of Tibet, China, by using standard assays to test mosquitoes, pigs, and
      humans. Results confirmed that JEV has spread to these areas. Disease prevention
      and control strategies should be used along with surveillance to limit spread of
      JEV in high-altitude regions of Tibet.

PMID- 28518048
TI  - The potential adverse effects of haemolysis.
AB  - Haemolysis occurs in many haematologic and non-haematologic diseases. Transfusion
      of packed red blood cells (pRBCs) can result in intravascular haemolysis, in
      which the RBCs are destroyed within the circulation, and extravascular
      haemolysis, in which RBCs are phagocytosed in the monocyte-macrophage system.
      This happens especially after RBCs have been stored under refrigerated conditions
      for long periods. The clinical implications and the relative contribution of
      intra- vs extra-vascular haemolysis are still a subject of debate. They have been
      associated with adverse effects in animal models, but it remains to be determined
      whether these may be involved in mediating adverse effects in humans.

PMID- 28518050
TI  - Acetylcholinesterase provides new insights into red blood cell ageing in vivo and
      in vitro.
AB  - BACKGROUND: During its 120 days sojourn in the circulation, the red blood cell
      (RBC) remodels its membrane. Acetylcholinesterase (AChE) is a
      glycosylphosphatidylinositol (GPI)-linked enzyme that may serve as a marker for
      membrane processes occurring this ageing-associated remodelling process.
      MATERIALS AND METHODS: Expression and enzymatic activity of AChE were determined
      on RBCs of various ages, as obtained by separation based on volume and density
      (ageing in vivo), and on RBCs of various times of storage in blood bank
      conditions (ageing in vitro), as well as on RBC-derived vesicles. RESULTS: During
      ageing in vivo, the enzymatic activity of AChE decreases, but not the AChE
      protein concentration. In contrast, neither AChE activity nor concentration show
      a consistent, significant decrease during ageing in vitro. CD59, another GPI
      linked protein that protects against complement-induced removal, also remains
      constant during storage. The cellular content of the integral membrane protein
      glycophorin A, however, decreases with storage time in the more dense RBC
      fractions. The latter are enriched in echinocytes and other misshapen cells
      during storage. DISCUSSION: Our findings suggest that, during RBC ageing, GPI
      linked proteins and integral membrane proteins are differentially sorted. Also,
      the vesicles that are generated in vitro show a fast and extensive loss of AChE
      activity, but not of AChE expression. Thus, AChE characteristics may constitute
      sensitive biomarkers of RBC ageing in vivo, and a source of information on the
      structural and functional changes that GPI-linked proteins undergo during ageing
      in vivo and in vitro. This information may help to understand RBC homeostasis and
      the effects of transfusion, especially in immunologically compromised patients.

PMID- 28518052
TI  - Italian consumption of plasma-derived factor VIII after the SIPPET study.

PMID- 28518051
TI  - Red blood cells ageing markers: a multi-parametric analysis.
AB  - BACKGROUND: Red blood cells collected in citrate-phosphate-dextrose can be stored
      for up to 42 days at 4  degrees C in saline-adenine-glucose-mannitol additive
      solution. During this controlled, but nevertheless artificial, ex vivo ageing,
      red blood cells accumulate lesions that can be reversible or irreversible upon
      transfusion. The aim of the present study is to follow several parameters
      reflecting cell metabolism, antioxidant defences, morphology and membrane
      dynamics during storage. MATERIALS AND METHODS: Five erythrocyte concentrates
      were followed weekly during 71 days. Extracellular glucose and lactate
      concentrations, total antioxidant power, as well as reduced and oxidised
      intracellular glutathione levels were quantified. Microvesiculation, percentage
      of haemolysis and haematologic parameters were also evaluated. Finally,
      morphological changes and membrane fluctuations were recorded using label-free
      digital holographic microscopy. RESULTS: The antioxidant power as well as the
      intracellular glutathione concentration first increased, reaching maximal values
      after one and two weeks, respectively. Irreversible morphological lesions
      appeared during week 5, where discocytes began to transform into transient
      echinocytes and finally spherocytes. At the same time, the microvesiculation and
      haemolysis started to rise exponentially. After six weeks (expiration date),
      intracellular glutathione was reduced by 25%, reflecting increasing oxidative
      stress. The membrane fluctuations showed decreased amplitudes during shape
      transition from discocytes to spherocytes. DISCUSSION: Various types of lesions
      accumulated at different chemical and cellular levels during storage, which could
      impact their in vivo recovery after transfusion. A marked effect was observed
      after four weeks of storage, which corroborates recent clinical data. The
      prolonged follow-up period allowed the capture of deep storage lesions.
      Interestingly, and as previously described, the severity of the changes differed
      among donors.

PMID- 28518053
TI  - Effects of genetic variants in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, ORM1 on
      PK/PD of telmisartan in Chinese patients with mild to moderate essential
      hypertension?.
AB  - PURPOSE: This study aimed to understand the effects of single nucleotide
      polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the
      pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood
      pressure) of telmisartan in Chinese patients. METHODS: 58 Han Chinese patients
      (aged 45 - 72 years) with mild to moderate essential hypertension were included
      and received 80 mg/day telmisartan for 4 weeks. The plasma concentration and
      genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry,
      respectively. Multivariable linear analysis was used to examine the relationships
      between PK/PD and genetic variants. RESULTS: Females showed a significantly
      higher AUC<sub>last</sub> than males (n = 22, 4,879.48 +/- 3,449.33 h*ng/mL vs. n
      = 36, 2,715.59 +/- 2,223.77 h*ng/mL, p = 0.047). Amongst all genetic variants
      investigated, the patients with UGT1A1 rs4124874 AA (n = 11, 1,730.51 +/-
      1,325.79 h*ng/mL) had a significantly lower AUC<sub>last</sub> compared with
      patients with UGT1A1 rs4124874 CC+AC (n = 19 + 28, 4,177.44 +/- 3,222.11 h*ng/mL
      and 3,810.82 +/- 2,960.43 h*ng/mL, p = 0.027). None of the SNPs investigated was
      associated with the PD responses to telmisartan. CONCLUSION: Variation of UGT1A1
      (rs4124874) affects PK of telmisartan in Chinese patients, highlighting the value
      of genetic testing in precision medicine as the telmisartan dose could be
      adjusted based on UGT1A1 genetic variations.?.

PMID- 28518049
TI  - Red blood cell storage time and transfusion: current practice, concerns and
      future perspectives.
AB  - Red blood cells (RBCs) units are the most requested transfusion product
      worldwide. Indications for transfusion include symptomatic anaemia, acute sickle
      cell crisis, and acute blood loss of more than 30% of the blood volume, with the
      aim of restoring tissue oxygen delivery. However, stored RBCs from donors are not
      a qualitative equal product, and, in many ways, this is a matter of concern in
      the transfusion practice. Besides donor-to-donor variation, the storage time
      influences the RBC unit at the qualitative level, as RBCs age in the storage bag
      and are exposed to the so-called storage lesion. Several studies have shown that
      the storage lesion leads to post-transfusion enhanced clearance, plasma
      transferrin saturation, nitric oxide scavenging and/or immunomodulation with
      potential unwanted transfusion-related clinical outcomes, such as acute lung
      injury or higher mortality rate. While, to date, several studies have claimed the
      risk or deleterious effects of "old" vs "young" RBC transfusion regimes, it is
      still a matter of debate, and consideration should be taken of the clinical
      context. Transfusion-dependent patients may benefit from transfusion with "young"
      RBC units, as it assures longer inter-transfusion periods, while transfusion with
      "old" RBC units is not itself harmful. Unbiased Omics approaches are being
      applied to the characterisation of RBC through storage, to better understand the
      (patho)physiological role of microparticles (MPs) that are found naturally, and
      also on stored RBC units. Perhaps RBC storage time is not an accurate surrogate
      for RBC quality and there is a need to establish which parameters do indeed
      reflect optimal efficacy and safety. A better Omics characterisation of
      components of "young" and "old" RBC units, including MPs, donor and recipient,
      might lead to the development of new therapies, including the use of engineered
      RBCs or MPs as cell-based drug delivering tools, or cost-effective personalised
      transfusion strategies.

PMID- 28518054
TI  - Comparison of three estimators for determining cyclosporine dosing in infants
      after liver transplantation?.
AB  - OBJECTIVE: To compare and analyze how allometrically- and linearly-scaled daily
      doses of cyclosporine could affect the therapeutic drug monitoring concentrations
      when applied to 8 infants with liver transplants. MATERIALS AND METHODS: Eight
      infants who underwent liver transplantations were put on twice-daily oral
      cyclosporine immunosuppressive regimens. After starting therapy, the adjustments
      of individual daily doses were determined by using therapeutic monitoring of
      plasma cyclosporine levels by measuring trough concentrations (C<sub>0</sub>) and
      concentrations at 2 hours after drug administration (C<sub>2</sub>). These doses
      were analyzed and compared with the hypothetical doses estimated by allometric
      and linear scaling in order to compare which of the two methods would yield
      closer estimates to the actual doses applied. RESULTS: The median therapeutic
      drug monitoring (TDM)-based dose (n = 53) was 70.00 mg (10.9 mg/kg/day) (5.00 -
      190.00 mg), whereas the median allometric (n = 53) and linear (n = 53) doses were
      65.21 mg (10.11 mg/kg/day) (57.17 - 79.25 mg) and 35.63 mg (5.52 mg/kg/day)
      (29.89 - 46.20 mg), respectively. The median allometric dose was significantly
      different than the median linear dose (p < 0.0001), whereas there was no
      statistical difference between the median TDM-based dose and median allometric
      dose (p = 0.72). CONCLUSIONS: The allometric approach, when used to estimate
      cyclosporine doses in this cohort of liver transplant infants, yielded closer
      estimates to actually applied daily doses in comparison to linear scaling.
      Allometric scaling could be employed in calculating starting doses for drugs that
      lack specific dosing recommendations for infants, in order to achieve therapeutic
      levels faster, lowering the need for constant monitoring and dose adjustment.?.

PMID- 28518058
TI  - Prediction of NSCLC recurrence from microarray data with GEP.
AB  - Lung cancer is one of the deadliest diseases in the world. Non-small cell lung
      cancer (NSCLC) is the most common and dangerous type of lung cancer. Despite the
      fact that NSCLC is preventable and curable for some cases if diagnosed at early
      stages, the vast majority of patients are diagnosed very late. Furthermore, NSCLC
      usually recurs sometime after treatment. Therefore, it is of paramount importance
      to predict NSCLC recurrence, so that specific and suitable treatments can be
      sought. Nonetheless, conventional methods of predicting cancer recurrence rely
      solely on histopathology data and predictions are not reliable in many cases. The
      microarray gene expression (GE) technology provides a promising and reliable way
      to predict NSCLC recurrence by analysing the GE of sample cells. This study
      proposes a new model from GE programming to use microarray datasets for NSCLC
      recurrence prediction. To this end, the authors also propose a hybrid method to
      rank and select relevant prognostic genes that are related to NSCLC recurrence
      prediction. The proposed model was evaluated on real NSCLC microarray datasets
      and compared with other representational models. The results demonstrated the
      effectiveness of the proposed model.

PMID- 28518056
TI  - Functionally diverse human T cells recognize non-microbial antigens presented by
      MR1.
AB  - MHC class I-related molecule MR1 presents riboflavin- and folate-related
      metabolites to mucosal-associated invariant T cells, but it is unknown whether
      MR1 can present alternative antigens to other T cell lineages. In healthy
      individuals we identified MR1-restricted T cells (named MR1T cells) displaying
      diverse TCRs and reacting to MR1-expressing cells in the absence of microbial
      ligands. Analysis of MR1T cell clones revealed specificity for distinct cell
      derived antigens and alternative transcriptional strategies for metabolic
      programming, cell cycle control and functional polarization following antigen
      stimulation. Phenotypic and functional characterization of MR1T cell clones
      showed multiple chemokine receptor expression profiles and secretion of diverse
      effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells
      exhibited distinct T helper-like capacities upon MR1-dependent recognition of
      target cells expressing physiological levels of surface MR1. These data extend
      the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are
      a normal part of the human T cell repertoire.

PMID- 28518057
TI  - On the mechanistic nature of epistasis in a canonical cis-regulatory element.
AB  - Understanding the relation between genotype and phenotype remains a major
      challenge. The difficulty of predicting individual mutation effects, and
      particularly the interactions between them, has prevented the development of a
      comprehensive theory that links genotypic changes to their phenotypic effects. We
      show that a general thermodynamic framework for gene regulation, based on a
      biophysical understanding of protein-DNA binding, accurately predicts the sign of
      epistasis in a canonical cis-regulatory element consisting of overlapping RNA
      polymerase and repressor binding sites. Sign and magnitude of individual mutation
      effects are sufficient to predict the sign of epistasis and its environmental
      dependence. Thus, the thermodynamic model offers the correct null prediction for
      epistasis between mutations across DNA-binding sites. Our results indicate that a
      predictive theory for the effects of cis-regulatory mutations is possible from
      first principles, as long as the essential molecular mechanisms and the
      constraints these impose on a biological system are accounted for.

PMID- 28518059
TI  - Recent omics technologies and their emerging applications for personalised
      medicine.
AB  - A major objective of 'omics' technologies is to understand genetic causality of
      complex traits of human diseases. High-throughput omics technologies and their
      application to medicine open up remarkable opportunities for realising optimised
      medical treatment for individuals. Because many major breakthrough and
      discoveries in this field have been driven by the development of new omics
      technologies, in this review, the authors aim to provide an in-depth description
      of their underlying principles as a foundation of developing another new omics
      technology, and to introduce their emerging applications for personalised
      medicine. The systems biology approach is then introduced as a future direction
      towards actionable personalised medicine.

PMID- 28518055
TI  - A positive feedback loop linking enhanced mGluR function and basal calcium in
      spinocerebellar ataxia type 2.
AB  - Metabotropic glutamate receptor 1 (mGluR1) function in Purkinje neurons (PNs) is
      essential for cerebellar development and for motor learning and altered mGluR1
      signaling causes ataxia. Downstream of mGluR1, dysregulation of calcium
      homeostasis has been hypothesized as a key pathological event in genetic forms of
      ataxia but the underlying mechanisms remain unclear. We find in a spinocerebellar
      ataxia type 2 (SCA2) mouse model that calcium homeostasis in PNs is disturbed
      across a broad range of physiological conditions. At parallel fiber synapses,
      mGluR1-mediated excitatory postsynaptic currents (EPSCs) and associated calcium
      transients are increased and prolonged in SCA2 PNs. In SCA2 PNs, enhanced mGluR1
      function is prevented by buffering [Ca2+] at normal resting levels while in
      wildtype PNs mGluR1 EPSCs are enhanced by elevated [Ca2+]. These findings
      demonstrate a deleterious positive feedback loop involving elevated intracellular
      calcium and enhanced mGluR1 function, a mechanism likely to contribute to PN
      dysfunction and loss in SCA2.

PMID- 28518060
TI  - Analysis of healthy and tumour DNA methylation distributions in kidney-renal
      clear-cell-carcinoma using Kullback-Leibler and Jensen-Shannon distance measures.
AB  - DNA methylation is an epigenetic phenomenon in which methyl groups get bonded to
      the cytosines of the DNA molecule altering the expression of the associated
      genes. Cancer is linked with hypo or hyper-methylation of specific genes as well
      as global changes in DNA methylation. In this study, the authors study the
      probability density function distribution of DNA methylation in various
      significant genes and across the genome in healthy and tumour samples. They
      propose a unique 'average healthy methylation distribution' based on the
      methylation values of several healthy samples. They then obtain the Kullback
      Leibler and Jensen-Shannon distances between methylation distributions of the
      healthy and tumour samples and the average healthy methylation distribution. The
      distance measures of the healthy and tumour samples from the average healthy
      methylation distribution are compared and the differences in the distances are
      analysed as possible parameters for cancer. A classifier trained on these values
      was found to provide high values of sensitivity and specificity. They consider
      this to be a computationally efficient approach to predict tumour samples based
      on DNA methylation data. This technique can also be improvised to consider other
      differentially methylated genes significant in cancer or other epigenetic
      diseases.

PMID- 28518061
TI  - Graft Quality and Prediction of Outcome After Liver Transplantation.

PMID- 28518062
TI  - Retrograde Flushing of Living Donor Renal Allografts via the Renal Vein: A
      Simple, Effective Technique.
AB  - BACKGROUND: Prograde flushing (PF) of living donor renal allografts with
      preservation solution via the renal artery or arteries is standard practice. PF
      may be difficult and potentially injurious to the donor kidney, especially in
      grafts with small or multiple arteries. In this report, we present our experience
      with retrograde flushing (RF) of 7 living donor kidneys via the renal vein.
      METHODS: Retrospective review of 7 consecutive living donor renal transplants
      performed using the RF technique was performed. The 7 preceding living donor
      renal transplants performed using the standard arterial PF technique served as a
      control group. RESULTS: All 7 recipients of RF kidneys experienced immediate
      graft function. At postoperative days 3 and 30, there was no difference in
      estimated glomerular filtration rate between the RF study group and PF controls.
      CONCLUSIONS: The RF technique is simple and safe, with results equivalent to the
      PF technique. The RF technique may be especially useful after recovering kidneys
      with small and/or multiple arteries.

PMID- 28518063
TI  - Visualizing Visual Adaptation.
AB  - Many techniques have been developed to visualize how an image would appear to an
      individual with a different visual sensitivity: e.g., because of optical or age
      differences, or a color deficiency or disease. This protocol describes a
      technique for incorporating sensory adaptation into the simulations. The protocol
      is illustrated with the example of color vision, but is generally applicable to
      any form of visual adaptation. The protocol uses a simple model of human color
      vision based on standard and plausible assumptions about the retinal and cortical
      mechanisms encoding color and how these adjust their sensitivity to both the
      average color and range of color in the prevailing stimulus. The gains of the
      mechanisms are adapted so that their mean response under one context is equated
      for a different context. The simulations help reveal the theoretical limits of
      adaptation and generate "adapted images" that are optimally matched to a specific
      environment or observer. They also provide a common metric for exploring the
      effects of adaptation within different observers or different environments.
      Characterizing visual perception and performance with these images provides a
      novel tool for studying the functions and consequences of long-term adaptation in
      vision or other sensory systems.

PMID- 28518064
TI  - An Experimental and Finite Element Protocol to Investigate the Transport of
      Neutral and Charged Solutes across Articular Cartilage.
AB  - Osteoarthritis (OA) is a debilitating disease that is associated with
      degeneration of articular cartilage and subchondral bone. Degeneration of
      articular cartilage impairs its load-bearing function substantially as it
      experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen
      fibril disruption. One promising way to investigate chemical damage mechanisms
      during OA is to expose the cartilage specimens to an external solute and monitor
      the diffusion of the molecules. The degree of cartilage damage (i.e.
      concentration and configuration of essential macromolecules) is associated with
      collisional energy loss of external solutes while moving across articular
      cartilage creates different diffusion characteristics compared to healthy
      cartilage. In this study, we introduce a protocol, which consists of several
      steps and is based on previously developed experimental micro-Computed Tomography
      (micro-CT) and finite element modeling. The transport of charged and uncharged
      iodinated molecules is first recorded using micro-CT, which is followed by
      applying biphasic-solute and multiphasic finite element models to obtain
      diffusion coefficients and fixed charge densities across cartilage zones.

PMID- 28518065
TI  - Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats.
AB  - A number of animal models have been used to study hypoxic-ischemic injury,
      traumatic injury, global hypoxia, or permanent ischemia in both the immature and
      mature brain. Stroke occurs commonly in the perinatal period in humans, and
      transient ischemia-reperfusion is the most common form of stroke in neonates. The
      reperfusion phase is a critical component of injury progression, which occurs
      over a period of days to weeks, and of the endogenous response to injury. This
      postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion
      (tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury
      that can be utilized to study the mechanisms of focal injury and repair in the
      full-term-equivalent brain. The injury pattern that is produced by tMCAO is
      consistent and highly reproducible and can be confirmed with MRI or histological
      analyses. The severity of injury can be manipulated through changes in occlusion
      time and other methods that will be discussed.

PMID- 28518066
TI  - Scaled Anatomical Model Creation of Biomedical Tomographic Imaging Data and
      Associated Labels for Subsequent Sub-surface Laser Engraving (SSLE) of Glass
      Crystals.
AB  - Biomedical imaging modalities like computed tomography (CT) and magnetic
      resonance (MR) provide excellent platforms for collecting three-dimensional data
      sets of patient or specimen anatomy in clinical or preclinical settings. However,
      the use of a virtual, on-screen display limits the ability of these tomographic
      images to fully convey the anatomical information embedded within. One solution
      is to interface a biomedical imaging data set with 3D printing technology to
      generate a physical replica. Here we detail a complementary method to visualize
      tomographic imaging data with a hand-held model: Sub Surface Laser Engraving
      (SSLE) of crystal glass. SSLE offers several unique benefits including: the
      facile ability to include anatomical labels, as well as a scale bar; streamlined
      multipart assembly of complex structures in one medium; high resolution in the X,
      Y, and Z planes; and semi-transparent shells for visualization of internal
      anatomical substructures. Here we demonstrate the process of SSLE with CT data
      sets derived from pre-clinical and clinical sources. This protocol will serve as
      a powerful and inexpensive new tool with which to visualize complex anatomical
      structures for scientists and students in a number of educational and research
      settings.

PMID- 28518067
TI  - Remote Sensing Evaluation of Two-spotted Spider Mite Damage on Greenhouse Cotton.
AB  - The objective of this study was to evaluate a ground-based multispectral optical
      sensor as a remote sensing tool to assess foliar damage caused by the two-spotted
      spider mite (TSSM), Tetranychus urticae Koch, on greenhouse grown cotton. TSSM is
      a polyphagous pest which occurs on a variety of field and horticultural crops. It
      often becomes an early season pest of cotton in damaging proportions as opposed
      to being a late season innocuous pest in the mid-southern United States.
      Evaluation of acaricides is important for maintaining the efficacy of and
      preventing resistance to the currently available arsenal of chemicals and newly
      developed control agents. Enumeration of spider mites for efficacy evaluations is
      laborious and time consuming. Therefore, subjective visual damage rating is
      commonly used to assess density of spider mites. The NDVI (Normalized Difference
      Vegetation Index) is the most widely used statistic to describe the spectral
      reflectance characteristics of vegetation canopy to assess plant stress and
      health consequent to spider mite infestations. Results demonstrated that a
      multispectral optical sensor is an effective tool in distinguishing varying
      levels of infestation caused by T. urticae on early season cotton. This remote
      sensing technique may be used in lieu of a visual rating to evaluate insecticide
      treatments.

PMID- 28518068
TI  - 3D Magnetic Stem Cell Aggregation and Bioreactor Maturation for Cartilage
      Regeneration.
AB  - Cartilage engineering remains a challenge due to the difficulties in creating an
      in vitro functional implant similar to the native tissue. An approach recently
      explored for the development of autologous replacements involves the
      differentiation of stem cells into chondrocytes. To initiate this chondrogenesis,
      a degree of compaction of the stem cells is required; hence, we demonstrated the
      feasibility of magnetically condensing cells, both within thick scaffolds and
      scaffold-free, using miniaturized magnetic field sources as cell attractors. This
      magnetic approach was also used to guide aggregate fusion and to build scaffold
      free, organized, three-dimensional (3D) tissues several millimeters in size. In
      addition to having an enhanced size, the tissue formed by magnetic-driven fusion
      presented a significant increase in the expression of collagen II, and a similar
      trend was observed for aggrecan expression. As the native cartilage was subjected
      to forces that influenced its 3D structure, dynamic maturation was also
      performed. A bioreactor that provides mechanical stimuli was used to culture the
      magnetically seeded scaffolds over a 21-day period. Bioreactor maturation largely
      improved chondrogenesis into the cellularized scaffolds; the extracellular matrix
      obtained under these conditions was rich in collagen II and aggrecan. This work
      outlines the innovative potential of magnetic condensation of labeled stem cells
      and dynamic maturation in a bioreactor for improved chondrogenic differentiation,
      both scaffold-free and within polysaccharide scaffolds.

PMID- 28518069
TI  - Modification and Functionalization of the Guanidine Group by Tailor-made
      Precursors.
AB  - The guanidine group is one of the most important pharmacophoric groups in
      medicinal chemistry. The only amino acid carrying a guanidine group is arginine.
      In this article, an easy method for the modification of the guanidine group in
      peptidic ligands is provided, with an example of RGD-binding integrin ligands. It
      was recently demonstrated that the distinct modification of the guanidine group
      in these ligands allows for the selective modulation of the subtype (e.g.,
      between the subtypes alphav and alpha5). Moreover, a formerly unknown strategy
      for the functionalization via the guanidine group was demonstrated, and the
      synthetic approach is reviewed in this document. The modifications described here
      involve terminally (Nomega) alkylated and acetylated guanidine groups. For the
      synthesis, tailor-made precursor molecules are synthesized, which are then
      subjected to a reaction with an orthogonally deprotected amine to transfer the
      pre-modified guanidine group. For the synthesis of alkylated guanidines,
      precursors based on N,N'-Di-Boc-1H-pyrazole-1-carboxamidine are used to
      synthesize acylated compounds, the precursor of choice being a correspondingly
      acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one-
      and two-step reactions.

PMID- 28518070
TI  - Sample Preparation for Mass Cytometry Analysis.
AB  - Mass cytometry utilizes antibodies conjugated with heavy metal labels, an
      approach that has greatly increased the number of parameters and opportunities
      for deep analysis well beyond what is possible with conventional fluorescence
      based flow cytometry. As with any new technology, there are critical steps that
      help ensure the reliable generation of high-quality data. Presented here is an
      optimized protocol that incorporates multiple techniques for the processing of
      cell samples for mass cytometry analysis. The methods described here will help
      the user avoid common pitfalls and achieve consistent results by minimizing
      variability, which can lead to inaccurate data. To inform experimental design,
      the rationale behind optional or alternative steps in the protocol and their
      efficacy in uncovering new findings in the biology of the system being
      investigated is covered. Lastly, representative data is presented to illustrate
      expected results from the techniques presented here.

PMID- 28518071
TI  - Nerve-sparing Mid-urethral Obstruction (NeMO) in Female Small Rodents.
AB  - Partial bladder outlet obstruction (pBOO) has a high prevalence, causes
      significant patient burden, and immense health care costs. The most common animal
      model to investigate bladder remodeling in pBOO are female rodents undergoing
      partial obstruction at the proximal urethra. Variability in the degree of
      obstruction and animal mortality are major concerns with proximal obstruction.
      Furthermore, dissecting around the proximal urethra and bladder neck jeopardizes
      bladder innervation. We developed a nerve-sparing mid-urethral obstruction (NeMO)
      model for pBOO avoiding the disadvantages of the traditional model. We approached
      the urethra just inferior to the pubic symphysis, which obviated the need for
      laparotomy as well as for dissection in this area; also, the striated urethral
      sphincter remained untouched. We performed NeMO in female Sprague-Dawley rats (12
      obstructions, 6 sham animals) as well as in female C57/bl6 mice (20 obstructions,
      18 sham animals). After two weeks, we evaluated bladder function, bladder mass,
      and body mass. We had no mortalities among obstructed- or sham-operated female
      rats; as described for the traditional proximal pBOO-method, we tied the suture
      around the proximal urethra and a temporarily placed 0.9 mm metal rod. NeMO
      induced an 85% increase in bladder mass after two weeks, average residual urine
      volume was 0.4 mL in partially obstructed rats while only 0.03 mL in sham
      animals. In mice, we tested 3 sizes of cannulas that we placed along the urethra
      when tying the suture. We found that using a 27-gauge cannula resulted in over
      50% animal mortality; placing the 25-gauge cannula did not yield the desired
      response in increasing bladder mass; utilizing a 26-gauge cannula yielded
      favorable results with minimal animal mortality (1/8) yet a significant 2-fold
      increase in bladder mass.

PMID- 28518072
TI  - In Vivo Investigation of Antimicrobial Blue Light Therapy for Multidrug-resistant
      Acinetobacter baumannii Burn Infections Using Bioluminescence Imaging.
AB  - Burn infections continue to be an important cause of morbidity and mortality. The
      increasing emergence of multidrug-resistant (MDR) bacteria has led to the
      frequent failure of traditional antibiotic treatments. Alternative therapeutics
      are urgently needed to tackle MDR bacteria. An innovative non-antibiotic
      approach, antimicrobial blue light (aBL), has shown promising effectiveness
      against MDR infections. The mechanism of action of aBL is not yet well
      understood. It is commonly hypothesized that naturally occurring endogenous
      photosensitizing chromophores in bacteria (e.g., iron-free porphyrins, flavins,
      etc.) are excited by aBL, which in turn produces cytotoxic reactive oxygen
      species (ROS) through a photochemical process. Unlike another light-based
      antimicrobial approach, antimicrobial photodynamic therapy (aPDT), aBL therapy
      does not require the involvement of an exogenous photosensitizer. All it needs to
      take effect is the irradiation of blue light; therefore, it is simple and
      inexpensive. The aBL receptors are the endogenous cellular photosensitizers in
      bacteria, rather than the DNA. Thus, aBL is believed to be much less genotoxic to
      host cells than ultraviolet-C (UVC) irradiation, which directly causes DNA damage
      in host cells. In this paper, we present a protocol to assess the effectiveness
      of aBL therapy for MDR Acinetobacter baumannii infections in a mouse model of
      burn injury. By using an engineered bioluminescent strain, we were able to
      noninvasively monitor the extent of infection in real time in living animals.
      This technique is also an effective tool for monitoring the spatial distribution
      of infections in animals.

PMID- 28518073
TI  - Extraction and Characterization of Surfactants from Atmospheric Aerosols.
AB  - Surface-active compounds, or surfactants, present in atmospheric aerosols are
      expected to play important roles in the formation of liquid water clouds in the
      Earth's atmosphere, a central process in meteorology, hydrology, and for the
      climate system. But because specific extraction and characterization of these
      compounds have been lacking for decades, very little is known on their identity,
      properties, mode of action and origins, thus preventing the full understanding of
      cloud formation and its potential links with the Earth's ecosystems. In this
      paper we present recently developed methods for 1) the targeted extraction of all
      the surfactants from atmospheric aerosol samples and for the determination of 2)
      their absolute concentrations in the aerosol phase and 3) their static surface
      tension curves in water, including their Critical Micelle Concentration (CMC).
      These methods have been validated with 9 references surfactants, including
      anionic, cationic and non-ionic ones. Examples of results are presented for
      surfactants found in fine aerosol particles (diameter <1 MUm) collected at a
      coastal site in Croatia and suggestions for future improvements and other
      characterizations than those presented are discussed.

PMID- 28518075
TI  - Leveraging CyVerse Resources for De Novo Comparative Transcriptomics of
      Underserved (Non-model) Organisms.
AB  - This workflow allows novice researchers to leverage advanced computational
      resources such as cloud computing to carry out pairwise comparative
      transcriptomics. It also serves as a primer for biologists to develop data
      scientist computational skills, e.g. executing bash commands, visualization and
      management of large data sets. All command line code and further explanations of
      each command or step can be found on the wiki
      (https://wiki.cyverse.org/wiki/x/dgGtAQ). The Discovery Environment and
      Atmosphere platforms are connected together through the CyVerse Data Store. As
      such, once the initial raw sequencing data has been uploaded there is no more
      need to transfer large data files over an Internet connection, minimizing the
      amount of time needed to conduct analyses. This protocol is designed to analyze
      only two experimental treatments or conditions. Differential gene expression
      analysis is conducted through pairwise comparisons, and will not be suitable to
      test multiple factors. This workflow is also designed to be manual rather than
      automated. Each step must be executed and investigated by the user, yielding a
      better understanding of data and analytical outputs, and therefore better results
      for the user. Once complete, this protocol will yield de novo assembled
      transcriptome(s) for underserved (non-model) organisms without the need to map to
      previously assembled reference genomes (which are usually not available in
      underserved organism). These de novo transcriptomes are further used in pairwise
      differential gene expression analysis to investigate genes differing between two
      experimental conditions. Differentially expressed genes are then functionally
      annotated to understand the genetic response organisms have to experimental
      conditions. In total, the data derived from this protocol is used to test
      hypotheses about biological responses of underserved organisms.

PMID- 28518074
TI  - Eliciting and Analyzing Male Mouse Ultrasonic Vocalization (USV) Songs.
AB  - Mice produce ultrasonic vocalizations (USVs) in a variety of social contexts
      throughout development and adulthood. These USVs are used for mother-pup
      retrieval1, juvenile interactions2, opposite and same sex interactions3,4,5, and
      territorial interactions6. For decades, the USVs have been used by investigators
      as proxies to study neuropsychiatric and developmental or behavioral
      disorders7,8,9, and more recently to understand mechanisms and evolution of vocal
      communication among vertebrates10. Within the sexual interactions, adult male
      mice produce USV songs, which have some features similar to courtship songs of
      songbirds11. The use of such multisyllabic repertoires can increase potential
      flexibility and information they carry, as they can be varied in how elements are
      organized and recombined, namely syntax. In this protocol a reliable method to
      elicit USV songs from male mice in various social contexts, such as exposure to
      fresh female urine, anesthetized animals, and estrus females is described. This
      includes conditions to induce a large amount of syllables from the mice. We
      reduce recording of ambient noises with inexpensive sound chambers, and present a
      quantification method to automatically detect, classify and analyze the USVs. The
      latter includes evaluation of call-rate, vocal repertoire, acoustic parameters,
      and syntax. Various approaches and insight on using playbacks to study an
      animal's preference for specific song types are described. These methods were
      used to describe acoustic and syntax changes across different contexts in male
      mice, and song preferences in female mice.

PMID- 28518076
TI  - Facile Preparation of Ultrafine Aluminum Hydroxide Particles with or without
      Mesoporous MCM-41 in Ambient Environments.
AB  - An aqueous suspension of nanogibbsite was synthesized via the titration of
      aluminum aqua acid [Al(H2O)6]3+ with L-arginine to pH 4.6. Since the hydrolysis
      of aqueous aluminum salts is known to produce a wide array of products with a
      wide range of size distributions, a variety of state-of-the-art instruments
      (i.e., 27Al/1H NMR, FTIR, ICP-OES, TEM-EDX, XPS, XRD, and BET) were used to
      characterize the synthesis products and identification of byproducts. The
      product, which was comprised of nanoparticles (10-30 nm), was isolated using gel
      permeation chromatography (GPC) column technique. Fourier transform infrared
      (FTIR) spectroscopy and powder X-ray diffraction (PXRD) identified the purified
      material as the gibbsite polymorph of aluminum hydroxide. The addition of
      inorganic salts (e.g., NaCl) induced electrostatic destabilization of the
      suspension, thereby agglomerating the nanoparticles to yield Al(OH)3 precipitate
      with large particle sizes. By utilizing the novel synthetic method described
      here, Al(OH)3 was partially loaded inside the highly ordered mesoporous framework
      of MCM-41, with average pore dimensions of 2.7 nm, producing an aluminosilicate
      material with both octahedral and tetrahedral Al (Oh/Td = 1.4). The total Al
      content, measured using energy-dispersive X-ray spectrometry (EDX), was 11% w/w
      with a Si/Al molar ratio of 2.9. A comparison of bulk EDX with surface X-ray
      photoelectron spectroscopy (XPS) elemental analysis provided insight into the
      distribution of Al within the aluminosilicate material. Furthermore, a higher
      ratio of Si/Al was observed on the external surface (3.6) as compared to the bulk
      (2.9). Approximations of O/Al ratios suggest a higher concentration of Al(O)3 and
      Al(O)4 groups near the core and external surface, respectively. The newly
      developed synthesis of Al-MCM-41 yields a relatively high Al content while
      maintaining the integrity of the ordered silica framework and can be used for
      applications where hydrated or anhydrous Al2O3 nanoparticles are advantageous.

PMID- 28518077
TI  - Inkjet-printed Polyvinyl Alcohol Multilayers.
AB  - Inkjet printing is a modern method for polymer processing, and in this work, we
      demonstrate that this technology is capable of producing polyvinyl alcohol (PVOH)
      multilayer structures. A polyvinyl alcohol aqueous solution was formulated. The
      intrinsic properties of the ink, such as surface tension, viscosity, pH, and time
      stability, were investigated. The PVOH-based ink was a neutral solution (pH 6.7)
      with a surface tension of 39.3 mN/m and a viscosity of 7.5 cP. The ink displayed
      pseudoplastic (non-Newtonian shear thinning) behavior at low shear rates, and
      overall, it demonstrated good time stability. The wettability of the ink on
      different substrates was investigated, and glass was identified as the most
      suitable substrate in this particular case. A proprietary 3D inkjet printer was
      employed to manufacture polymer multilayer structures. The morphology, surface
      profile, and thickness uniformity of inkjet-printed multilayers were evaluated
      via optical microscopy.

PMID- 28518078
TI  - Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity
      Using an Activatable Fluorescent Imaging Agent.
AB  - This paper describes a non-invasive method for imaging matrix metalloproteinases
      (MMP)-activity by an activatable fluorescent probe, via in vivo fluorescence
      optical imaging (OI), in two different mouse models of inflammation: a rheumatoid
      arthritis (RA) and a contact hypersensitivity reaction (CHR) model. Light with a
      wavelength in the near infrared (NIR) window (650 - 950 nm) allows a deeper
      tissue penetration and minimal signal absorption compared to wavelengths below
      650 nm. The major advantages using fluorescence OI is that it is cheap, fast and
      easy to implement in different animal models. Activatable fluorescent probes are
      optically silent in their inactivated states, but become highly fluorescent when
      activated by a protease. Activated MMPs lead to tissue destruction and play an
      important role for disease progression in delayed-type hypersensitivity reactions
      (DTHRs) such as RA and CHR. Furthermore, MMPs are the key proteases for cartilage
      and bone degradation and are induced by macrophages, fibroblasts and chondrocytes
      in response to pro-inflammatory cytokines. Here we use a probe that is activated
      by the key MMPs like MMP-2, -3, -9 and -13 and describe an imaging protocol for
      near infrared fluorescence OI of MMP activity in RA and control mice 6 days after
      disease induction as well as in mice with acute (1x challenge) and chronic (5x
      challenge) CHR on the right ear compared to healthy ears.

PMID- 28518080
TI  - Rearing Ixodes scapularis, the Black-legged Tick: Feeding Immature Stages on
      Mice.
AB  - Ixodes scapularis, the vector of Lyme disease, is one of the most important
      disease vectors in the eastern and Midwestern United States. This species is a
      three host tick that requires a blood meal from a vertebrate host for each
      development stage, and the adult females require a blood meal for reproduction.
      Larval ticks attach to their host for 3 - 5 days for feeding and drop off the
      host when fully engorged. This dependency on several different hosts and the
      lengthy attachment time for engorgement complicates tick rearing in the
      laboratory setting. However, to understand tick biology and tick-pathogen
      interactions, the production of healthy, laboratory-reared ticks is essential.
      Here, we demonstrate a simple, cost-effective protocol for immature tick feeding
      on mice. We modified the existing protocols for decreased stress on mice and
      increased tick feeding success and survival by using disposable cages without
      mesh bottoms to avoid contact of ticks with water contaminated with mice urine
      and feces.

PMID- 28518079
TI  - A Method for Quantifying Upper Limb Performance in Daily Life Using
      Accelerometers.
AB  - A key reason for referral to rehabilitation services after stroke and other
      neurological conditions is to improve one's ability to function in daily life. It
      has become important to measure a person's activities in daily life, and not just
      measure their capacity for activity in the structured environment of a clinic or
      laboratory. A wearable sensor that is now enabling measurement of daily movement
      is the accelerometer. Accelerometers are commercially-available devices
      resembling large wrist watches that can be worn throughout the day. Data from
      accelerometers can quantify how the limbs are engaged to perform activities in
      peoples' homes and communities. This report describes a methodology to collect
      accelerometry data and turn it into clinically-relevant information. First, data
      are collected by having the participant wear two accelerometers (one on each
      wrist) for 24 h or longer. The accelerometry data are then downloaded and
      processed to produce four different variables that describe key aspects of upper
      limb activity in daily life: hours of use, use ratio, magnitude ratio, and the
      bilateral magnitude. Density plots can be constructed that visually represent the
      data from the 24 h wearing period. The variables and their resultant density
      plots are highly consistent in neurologically-intact, community-dwelling adults.
      This striking consistency makes them a useful tool for determining if upper limb
      daily performance is different from normal. This methodology is appropriate for
      research studies investigating upper limb dysfunction and interventions designed
      to improve upper limb performance in daily life in people with stroke and other
      patient populations. Because of its relative simplicity, it may not be long
      before it is also incorporated in clinical neurorehabilitation practice.

PMID- 28518081
TI  - Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT.
AB  - This paper describes the use of 18F-FDG and micro-PET/CT imaging to determine in
      vivo glucose metabolism kinetics in mice (and is transferable to rats). Impaired
      uptake and metabolism of glucose in multiple organ systems due to insulin
      resistance is a hallmark of type 2 diabetes. The ability of this technique to
      extract an image-derived input function from the vena cava using an iterative
      deconvolution method eliminates the requirement of the collection of arterial
      blood samples. Fitting of tissue and vena cava time activity curves to a two
      tissue, three compartment model permits the estimation of kinetic micro
      parameters related to the 18F-FDG uptake from the plasma to the intracellular
      space, the rate of transport from intracellular space to plasma and the rate of
      18F-FDG phosphorylation. This methodology allows for multiple measures of glucose
      uptake and metabolism kinetics in the context of longitudinal studies and also
      provides insights into the efficacy of therapeutic interventions.

PMID- 28518082
TI  - Maturation of Human Stem Cell-derived Cardiomyocytes in Biowires Using Electrical
      Stimulation.
AB  - Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been a
      promising cell source and have thus encouraged the investigation of their
      potential applications in cardiac research, including drug discovery, disease
      modeling, tissue engineering, and regenerative medicine. However, cells produced
      by existing protocols display a range of immaturity compared with native adult
      ventricular cardiomyocytes. Many efforts have been made to mature hPSC-CMs, with
      only moderate maturation attained thus far. Therefore, an engineered system,
      called biowire, has been devised by providing both physical and electrical cues
      to lead hPSC-CMs to a more mature state in vitro. The system uses a
      microfabricated platform to seed hPSC-CMs in collagen type I gel along a rigid
      template suture to assemble into aligned cardiac tissue (biowire), which is
      subjected to electrical field stimulation with a progressively increasing
      frequency. Compared to nonstimulated controls, stimulated biowired cardiomyocytes
      exhibit an enhanced degree of structural and electrophysiological maturation.
      Such changes are dependent upon the stimulation rate. This manuscript describes
      in detail the design and creation of biowires.

PMID- 28518083
TI  - Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration.
AB  - Bronchoalveolar Lavage (BAL) is an experimental procedure that is used to examine
      the cellular and acellular content of the lung lumen ex vivo to gain insight into
      an ongoing disease state. Here, a simple and efficient method is described to
      perform BAL on murine lungs without the need of special tools or equipment. BAL
      fluid is isolated by inserting a catheter in the trachea of terminally
      anesthetized mice, through which a saline solution is instilled into the
      bronchioles. The instilled fluid is gently retracted to maximize BAL fluid
      retrieval and to minimize shearing forces. This technique allows the viability,
      function, and structure of cells within the airways and BAL fluid to be
      preserved. Numerous techniques may be applied to gain further understanding of
      the disease state of the lung. Here, a commonly used technique for the
      identification and enumeration of different types of immune cells is described,
      where flow cytometry is combined with a select panel of fluorescently labeled
      cell surface-specific markers. The BAL procedure presented here can also be used
      to analyze infectious agents, fluid constituents, or inhaled particles within
      murine lungs.

PMID- 28518084
TI  - Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain.
AB  - Chronic or neuropathic trigeminal facial pain can be challenging to treat.
      Neurosurgical procedures should be applied when conservative treatment fails.
      Neuromodulation techniques for chronic facial pain include deep brain stimulation
      and motor cortex stimulation, which are complex to perform. Subcutaneous nerve
      field stimulation is certified for chronic back pain and is the least invasive
      form of neuromodulation. We applied this technique to treat chronic and
      neuropathic trigeminal pain as an individual therapy concept. First, trial
      stimulation is performed. Subcutaneous leads are placed in the painful trigeminal
      dermatome under local anesthesia. The leads are connected to an external
      neurostimulator that applies constant stimulation. Patients undergo a 12 day
      outpatient trial to assess the effect of the stimulation. Electrodes are removed
      after the trial. If the patient reports pain reduction of at least 50% in
      intensity and/or attack frequency, a reduction in medication or increase in
      quality of life, permanent implantation is scheduled. New electrodes are
      implanted under general anesthesia and are subcutaneously tunneled to an
      infraclavicular internal pulse generator. Patients are able to turn stimulation
      on and off and to increase or decrease the stimulation amplitude as needed. This
      technique represents a minimal invasive alternative to other more invasive means
      of neuromodulation for trigeminal pain such as motor cortex stimulation or deep
      brain stimulation.

PMID- 28518085
TI  - Analysis of Chromosome Segregation, Histone Acetylation, and Spindle Morphology
      in Horse Oocytes.
AB  - The field of assisted reproduction has been developed to treat infertility in
      women, companion animals, and endangered species. In the horse, assisted
      reproduction also allows for the production of embryos from high performers
      without interrupting their sports career and contributes to an increase in the
      number of foals from mares of high genetic value. The present manuscript
      describes the procedures used for collecting immature and mature oocytes from
      horse ovaries using ovum pick-up (OPU). These oocytes were then used to
      investigate the incidence of aneuploidy by adapting a protocol previously
      developed in mice. Specifically, the chromosomes and the centromeres of metaphase
      II (MII) oocytes were fluorescently labeled and counted on sequential focal plans
      after confocal laser microscope scanning. This analysis revealed a higher
      incidence in the aneuploidy rate when immature oocytes were collected from the
      follicles and matured in vitro compared to in vivo. Immunostaining for tubulin
      and the acetylated form of histone four at specific lysine residues also revealed
      differences in the morphology of the meiotic spindle and in the global pattern of
      histone acetylation. Finally, the expression of mRNAs coding for histone
      deacetylases (HDACs) and acetyl-transferases (HATs) was investigated by reverse
      transcription and quantitative-PCR (q-PCR). No differences in the relative
      expression of transcripts were observed between in vitro and in vivo matured
      oocytes. In agreement with a general silencing of the transcriptional activity
      during oocyte maturation, the analysis of the total transcript amount can only
      reveal mRNA stability or degradation. Therefore, these findings indicate that
      other translational and post-translational regulations might be affected.
      Overall, the present study describes an experimental approach to morphologically
      and biochemically characterize the horse oocyte, a cell type that is extremely
      challenging to study due to low sample availability. However, it can expand our
      knowledge on the reproductive biology and infertility in monovulatory species.

PMID- 28518086
TI  - PTR-ToF-MS Coupled with an Automated Sampling System and Tailored Data Analysis
      for Food Studies: Bioprocess Monitoring, Screening and Nose-space Analysis.
AB  - Proton Transfer Reaction (PTR), combined with a Time-of-Flight (ToF) Mass
      Spectrometer (MS) is an analytical approach based on chemical ionization that
      belongs to the Direct-Injection Mass Spectrometric (DIMS) technologies. These
      techniques allow the rapid determination of volatile organic compounds (VOCs),
      assuring high sensitivity and accuracy. In general, PTR-MS requires neither
      sample preparation nor sample destruction, allowing real time and non-invasive
      analysis of samples. PTR-MS are exploited in many fields, from environmental and
      atmospheric chemistry to medical and biological sciences. More recently, we
      developed a methodology based on coupling PTR-ToF-MS with an automated sampler
      and tailored data analysis tools, to increase the degree of automation and,
      consequently, to enhance the potential of the technique. This approach allowed us
      to monitor bioprocesses (e.g. enzymatic oxidation, alcoholic fermentation), to
      screen large sample sets (e.g. different origins, entire germoplasms) and to
      analyze several experimental modes (e.g. different concentrations of a given
      ingredient, different intensities of a specific technological parameter) in terms
      of VOC content. Here, we report the experimental protocols exemplifying different
      possible applications of our methodology: i.e. the detection of VOCs released
      during lactic acid fermentation of yogurt (on-line bioprocess monitoring), the
      monitoring of VOCs associated with different apple cultivars (large-scale
      screening), and the in vivo study of retronasal VOC release during coffee
      drinking (nosespace analysis).

PMID- 28518087
TI  - Multimer-PAGE: A Method for Capturing and Resolving Protein Complexes in
      Biological Samples.
AB  - There are many well-developed methods for purifying and studying single proteins
      and peptides. However, most cellular functions are carried out by networks of
      interacting protein complexes, which are often difficult to investigate because
      their binding is non-covalent and easily perturbed by purification techniques.
      This work describes a method of stabilizing and separating native protein
      complexes from unmodified tissue using two-dimensional polyacrylamide gel
      electrophoresis. Tissue lysate is loaded onto a non-denaturing blue-native
      polyacrylamide gel, then an electric current is applied until the protein
      migrates a short distance into the gel. The gel strip containing the migrated
      protein is then excised and incubated with the amine-reactive cross-linking
      reagent dithiobis(succinimidyl propionate), which covalently stabilizes protein
      complexes. The gel strip containing cross-linked complexes is then cast into a
      sodium dodecyl sulfate polyacrylamide gel, and the complexes are separated
      completely. The method relies on techniques and materials familiar to most
      molecular biologists, meaning it is inexpensive and easy to learn. While it is
      limited in its ability to adequately separate extremely large complexes, and has
      not been universally successful, the method was able to capture a wide variety of
      well-studied complexes, and is likely applicable to many systems of interest.

PMID- 28518088
TI  - In Vitro Methods for Comparing Target Binding and CDC Induction Between
      Therapeutic Antibodies: Applications in Biosimilarity Analysis.
AB  - Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of
      different pathologies, including cancers. The development of biosimilar mAbs by
      pharmaceutical companies is a market opportunity, but it is also a strategy to
      increase drug accessibility and reduce therapy-associated costs. The protocols
      detailed here describe the evaluation of target binding and CDC induction by
      rituximab in Daudi cells. These two functions require different structural
      regions of the antibody and are relevant to the clinical effect induced by
      rituximab. The protocols allow the side-to-side comparison of a reference
      rituximab and a marketed rituximab biosimilar. The evaluated products showed
      differences both in target binding and CDC induction, suggesting that there are
      underlying physicochemical differences and highlighting the need to analyze the
      impact of those differences in the clinical setting. The methods reported here
      constitute simple and inexpensive in vitro models for the evaluation of the
      activity of rituximab biosimilars. Thus, they can be useful during biosimilar
      development, as well as for quality control in biosimilar production.
      Furthermore, the presented methods can be extrapolated to other therapeutic mAbs.

PMID- 28518089
TI  - Laparoscopic Technique for Serial Collection of Liver and Mesenteric Lymph Nodes
      in Macaques.
AB  - The mesenteric lymph nodes (MLN) and the liver are exposed to microbes and
      microbial products from the gastrointestinal (GI) tract, making them
      immunologically unique. The GI tract and associated MLN are sites of early viral
      replication in human immunodeficiency virus (HIV) infection and the MLN are
      likely important reservoir sites that harbor latently-infected cells even after
      prolonged antiretroviral therapy (ART). The liver has been shown to play a
      significant role in immune responses to lentiviruses and appears to play a
      significant role in clearance of virus from circulation. Nonhuman primate (NHP)
      models for HIV and Acquired Immunodeficiency Syndrome (AIDS) closely mimic these
      aspects of HIV infection and serial longitudinal sampling of primary sites of
      viral replication and the associated immune responses in this model will help to
      elucidate critical events in infection, pathogenesis, and the impact of various
      intervention strategies on these events. Current published techniques to sample
      liver and MLN together involve major surgery and/or necropsy, which limits the
      ability to investigate these important sites in a serial fashion in the same
      animal. We have previously described a laparoscopic technique for collection of
      MLN. Here, we describe a minimally invasive laparoscopic technique for serial
      longitudinal sampling of liver and MLN through the same two port locations
      required for the collection of MLN. The use of the same two ports minimizes the
      impact to the animals as no additional incisions are required. This technique can
      be used with increased sampling frequency compared to major abdominal surgery and
      reduces the potential for surgical complications and associated local and
      systemic inflammatory responses that could complicate interpretation of results.
      This procedure has potential to facilitate studies involving NHP models while
      improving animal welfare.

PMID- 28518090
TI  - Flash-and-Freeze: A Novel Technique to Capture Membrane Dynamics with Electron
      Microscopy.
AB  - Cells constantly change their membrane architecture and protein distribution, but
      it is extremely difficult to visualize these events at a temporal and spatial
      resolution on the order of ms and nm, respectively. We have developed a time
      resolved electron microscopy technique, "flash-and-freeze," that induces cellular
      events with optogenetics and visualizes the resulting membrane dynamics by
      freezing cells at defined time points after stimulation. To demonstrate this
      technique, we expressed channelrhodopsin, a light-sensitive cation channel, in
      mouse hippocampal neurons. A flash of light stimulates neuronal activity and
      induces neurotransmitter release from synaptic terminals through the fusion of
      synaptic vesicles. The optogenetic stimulation of neurons is coupled with high
      pressure freezing to follow morphological changes during synaptic transmission.
      Using a commercial instrument, we captured the fusion of synaptic vesicles and
      the recovery of the synaptic vesicle membrane. To visualize the sequence of
      events, large datasets were generated and analyzed blindly, since morphological
      changes were followed in different cells over time. Nevertheless, flash-and
      freeze allows the visualization of membrane dynamics in electron micrographs with
      ms temporal resolution.

PMID- 28518091
TI  - Long-term Live Imaging of Drosophila Eye Disc.
AB  - Live imaging provides the ability to continuously track dynamic cellular and
      developmental processes in real time. Drosophila larval imaginal discs have been
      used to study many biological processes, such as cell proliferation,
      differentiation, growth, migration, apoptosis, competition, cell-cell signaling,
      and compartmental boundary formation. However, methods for the long-term ex vivo
      culture and live imaging of the imaginal discs have not been satisfactory,
      despite many efforts. Recently, we developed a method for the long-term ex vivo
      culture and live imaging of imaginal discs for up to 18 h. In addition to using a
      high insulin concentration in the culture medium, a low-melting agarose was also
      used to embed the disc to prevent it from drifting during the imaging period.
      This report uses the eye-antennal discs as an example. Photoreceptor R3/4
      specific mdelta0.5-Ga4 expression was followed to demonstrate that photoreceptor
      differentiation and ommatidial rotation can be observed during a 10 h live
      imaging period. This is a detailed protocol describing this simple method.

PMID- 28518092
TI  - Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic
      Leukemia in Zebrafish.
AB  - Heterogeneous cell populations, from either healthy or malignant tissues, may
      contain a population of cells characterized by a differential ability to efflux
      the DNA-binding dye Hoechst 33342. This "side population" of cells can be
      identified using flow cytometric methods after the Hoechst 33342 dye is excited
      by an ultraviolet (UV) laser. The side population of many cell types contains
      stem- or progenitor-like cells. However, not all cell types have an identifiable
      side population. Danio rerio, zebrafish, have a robust in vivo model of T-cell
      acute lymphoblastic leukemia (T-ALL), but whether these zebrafish T-ALLs have a
      side population is unknown. The method described here outlines how to isolate the
      side population cells in zebrafish T-ALL. To begin, the T-ALL in zebrafish is
      generated via the microinjection of tol2 plasmids into one-cell stage embryos.
      Once the tumors have grown to a stage at which they expand into more than half of
      the animal's body, the T-ALL cells can be harvested. The cells are then stained
      with Hoechst 33342 and examined by flow cytometry for side population cells. This
      method has broad applications in zebrafish T-ALL research. While there are no
      known cell surface markers in zebrafish that confirm whether these side
      population cells are cancer stem cell-like, in vivo functional transplantation
      assays are possible. Furthermore, single-cell transcriptomics could be applied to
      identify the genetic features of these side population cells.

PMID- 28518093
TI  - Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor
      Treating Fields (TTFields).
AB  - Tumor Treating Fields (TTFields) are an effective treatment modality delivered
      via the continuous, noninvasive application of low-intensity (1-3 V/cm),
      alternating electric fields in the frequency range of several hundred kHz. The
      study of TTFields in tissue culture is carried out using the TTFields in vitro
      application system, which allows for the application of electric fields of
      varying frequencies and intensities to ceramic Petri dishes with a high
      dielectric constant (E > 5,000). Cancerous cell lines plated on coverslips at the
      bottom of the ceramic Petri dishes are subjected to TTFields delivered in two
      orthogonal directions at various frequencies to facilitate treatment outcome
      tests, such as cell counts and clonogenic assays. The results presented in this
      report demonstrate that the optimal frequency of the TTFields with respect to
      both cell counts and clonogenic assays is 200 kHz for both ovarian and glioma
      cells.

PMID- 28518095
TI  - Use of a Central Venous Line for Fluids, Drugs and Nutrient Administration in a
      Mouse Model of Critical Illness.
AB  - This protocol describes a centrally catheterized mouse model of prolonged
      critical illness. We combine the cecal ligation and puncture method to induce
      sepsis with the use of a central venous line for fluids, drugs and nutrient
      administration to mimic the human clinical setting. Critically ill patients
      require intensive medical support in order to survive. While the majority of
      patients will recover within a few days, about a quarter of the patients need
      prolonged intensive care and are at high risk of dying from non-resolving
      multiple organ failure. Furthermore, the prolonged phase of critical illness is
      hallmarked by profound muscle weakness, and endocrine and metabolic changes, of
      which the pathogenesis is currently incompletely understood. The most widely used
      animal model in critical care research is the cecal ligation and puncture model
      to induce sepsis. This is a very reproducible model, with acute inflammatory and
      hemodynamic changes similar to human sepsis, which is designed to study the acute
      phase of critical illness. However, this model is hallmarked by a high lethality,
      which is different from the clinical human situation, and is not developed to
      study the prolonged phase of critical illness. Therefore, we adapted the
      technique by placing a central venous catheter in the jugular vein allowing us to
      administer clinically relevant supportive care, to better mimic the human
      clinical situation of critical illness. This mouse model requires an extensive
      surgical procedure and daily intensive care of the animals, but it results in a
      relevant model of the acute and prolonged phase of critical illness.

PMID- 28518094
TI  - A Within-subjects Experimental Protocol to Assess the Effects of Social Input on
      Infant EEG.
AB  - Despite the importance of social interactions for infant brain development,
      little research has assessed functional neural activation while infants socially
      interact. Electroencephalography (EEG) power is an advantageous technique to
      assess infant functional neural activation. However, many studies record infant
      EEG only during one baseline condition. This protocol describes a paradigm that
      is designed to comprehensively assess infant EEG activity in both social and
      nonsocial contexts as well as tease apart how different types of social inputs
      differentially relate to infant EEG. The within-subjects paradigm includes four
      controlled conditions. In the nonsocial condition, infants view objects on
      computer screens. The joint attention condition involves an experimenter
      directing the infant's attention to pictures. The joint attention condition
      includes three types of social input: language, face-to-face interaction, and the
      presence of joint attention. Differences in infant EEG between the nonsocial and
      joint attention conditions could be due to any of these three types of input.
      Therefore, two additional conditions (one with language input while the
      experimenter is hidden behind a screen and one with face-to-face interaction)
      were included to assess the driving contextual factors in patterns of infant
      neural activation. Representative results demonstrate that infant EEG power
      varied by condition, both overall and differentially by brain region, supporting
      the functional nature of infant EEG power. This technique is advantageous in that
      it includes conditions that are clearly social or nonsocial and allows for
      examination of how specific types of social input relate to EEG power. This
      paradigm can be used to assess how individual differences in age, affect,
      socioeconomic status, and parent-infant interaction quality relate to the
      development of the social brain. Based on the demonstrated functional nature of
      infant EEG power, future studies should consider the role of EEG recording
      context and design conditions that are clearly social or nonsocial.

PMID- 28518096
TI  - Invasive Behavior of Human Breast Cancer Cells in Embryonic Zebrafish.
AB  - In many cases, cancer patients do not die of a primary tumor, but rather because
      of metastasis. Although numerous rodent models are available for studying cancer
      metastasis in vivo, other efficient, reliable, low-cost models are needed to
      quickly access the potential effects of (epi)genetic changes or pharmacological
      compounds. As such, we illustrate and explain the feasibility of xenograft models
      using human breast cancer cells injected into zebrafish embryos to support this
      goal. Under the microscope, fluorescent proteins or chemically labeled human
      breast cancer cells are transplanted into transgenic zebrafish embryos, Tg
      (fli:EGFP), at the perivitelline space or duct of Cuvier (Doc) 48 h after
      fertilization. Shortly afterwards, the temporal-spatial process of cancer cell
      invasion, dissemination, and metastasis in the living fish body is visualized
      under a fluorescent microscope. The models using different injection sites, i.e.,
      perivitelline space or Doc are complementary to one another, reflecting the early
      stage (intravasation step) and late stage (extravasation step) of the multistep
      metastatic cascade of events. Moreover, peritumoral and intratumoral angiogenesis
      can be observed with the injection into the perivitelline space. The entire
      experimental period is no more than 8 days. These two models combine cell
      labeling, micro-transplantation, and fluorescence imaging techniques, enabling
      the rapid evaluation of cancer metastasis in response to genetic and
      pharmacological manipulations.

PMID- 28518098
TI  - Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in
      Human Cells.
AB  - The processing of most eukaryotic RNAs is mediated by RNA Binding Proteins (RBPs)
      with modular configurations, including an RNA recognition module, which
      specifically binds the pre-mRNA target and an effector domain. Previously, we
      have taken advantage of the unique RNA binding mode of the PUF domain in human
      Pumilio 1 to generate a programmable RNA binding scaffold, which was used to
      engineer various artificial RBPs to manipulate RNA metabolism. Here, a detailed
      protocol is described to construct Engineered Splicing Factors (ESFs) that are
      specifically designed to modulate the alternative splicing of target genes. The
      protocol includes how to design and construct a customized PUF scaffold for a
      specific RNA target, how to construct an ESF expression plasmid by fusing a
      designer PUF domain and an effector domain, and how to use ESFs to manipulate the
      splicing of target genes. In the representative results of this method, we have
      also described the common assays of ESF activities using splicing reporters, the
      application of ESF in cultured human cells, and the subsequent effect of splicing
      changes. By following the detailed protocols in this report, it is possible to
      design and generate ESFs for the regulation of different types of Alternative
      Splicing (AS), providing a new strategy to study splicing regulation and the
      function of different splicing isoforms. Moreover, by fusing different functional
      domains with a designed PUF domain, researchers can engineer artificial factors
      that target specific RNAs to manipulate various steps of RNA processing.

PMID- 28518099
TI  - Dissection of Larval Zebrafish Gonadal Tissue.
AB  - Although wild zebrafish possess a ZZ/ZW sex-determination system, domesticated
      zebrafish have lost the sex chromosome. They utilize a polygenic sex
      determination system, where several genes distributed throughout the genome
      collectively determine the sex identities of individual fish. Currently, the
      genes involved in regulating gonad development and how they work remain elusive.
      Normally, isolating gonadal tissue is the first step to examine the sex
      developmental processes. Here, we present a procedure to isolate gonadal tissue
      from 17 dpf (days post fertilization) and 25 dpf zebrafish larvae. The isolated
      gonadal tissue may be subsequently examined by morphology and gene expression
      profiling.

PMID- 28518097
TI  - Light Sheet-based Fluorescence Microscopy of Living or Fixed and Stained
      Tribolium castaneum Embryos.
AB  - The red flour beetle Tribolium castaneum has become an important insect model
      organism in developmental genetics and evolutionary developmental biology. The
      observation of Tribolium embryos with light sheet-based fluorescence microscopy
      has multiple advantages over conventional widefield and confocal fluorescence
      microscopy. Due to the unique properties of a light sheet-based microscope, three
      dimensional images of living specimens can be recorded with high signal-to-noise
      ratios and significantly reduced photo-bleaching as well as photo-toxicity along
      multiple directions over periods that last several days. With more than four
      years of methodological development and a continuous increase of data, the time
      seems appropriate to establish standard operating procedures for the usage of
      light sheet technology in the Tribolium community as well as in the insect
      community at large. This protocol describes three mounting techniques suitable
      for different purposes, presents two novel custom-made transgenic Tribolium lines
      appropriate for long-term live imaging, suggests five fluorescent dyes to label
      intracellular structures of fixed embryos and provides information on data post
      processing for the timely evaluation of the recorded data. Representative results
      concentrate on long-term live imaging, optical sectioning and the observation of
      the same embryo along multiple directions. The respective datasets are provided
      as a downloadable resource. Finally, the protocol discusses quality controls for
      live imaging assays, current limitations and the applicability of the outlined
      procedures to other insect species. This protocol is primarily intended for
      developmental biologists who seek imaging solutions that outperform standard
      laboratory equipment. It promotes the continuous attempt to close the gap between
      the technically orientated laboratories/communities, which develop and refine
      microscopy methodologically, and the life science laboratories/communities, which
      require 'plug-and-play' solutions to technical challenges. Furthermore, it
      supports an axiomatic approach that moves the biological questions into the
      center of attention.

PMID- 28518100
TI  - TiO2-coated Hollow Glass Microspheres with Superhydrophobic and High IR
      reflective Properties Synthesized by a Soft-chemistry Method.
AB  - This manuscript proposes a soft-chemistry method to develop superhydrophobic and
      highly IR-reflective hollow glass microspheres (HGM). The anatase TiO2 and a
      superhydrophobic agent were coated on the HGM surface in one step. TBT and PFOTES
      were selected as the Ti source and the superhydrophobic agent, respectively. They
      were both coated on the HGM, and after the hydrothermal process, the TBT turned
      to anatase TiO2. In this way, a PFOTES/TiO2-coated HGM (MCHGM) was prepared. For
      comparison, PFOTES single-coated HGM (F-SCHGM) and TiO2 single-coated HGM (Ti
      SCHGM) were synthesized as well. The PFOTES and TiO2 coatings on the HGM surface
      were demonstrated through X-ray diffraction (XRD), scanning electron microscopy
      (SEM), and energy-dispersive detector (EDS) characterizations. The MCHGM showed a
      higher contact angle (153 degrees ) but a lower sliding angle (16 degrees ) than
      F-SCHGM, with a contact angle of 141.2 degrees  and a sliding angle of 67 degrees
      . In addition, both Ti-SCHGM and MCHGM displayed similar IR reflectivity values,
      which were about 5.8% higher than the original HGM and F-SCHGM. Also, the PFOTES
      coating barely changed the thermal conductivity. Therefore, F-SCHGM, with a
      thermal conductivity of 0.0479 W/(m.K), was quite like the original HGM, which
      was 0.0475 W/(m.K). MCHGM and Ti-SCHGM were also similar. Their thermal
      conductivity values were 0.0543 W/(m.K) and 0.0543 W/(m.K), respectively. The
      TiO2 coating slightly increased the thermal conductivity, but with the increase
      in reflectivity, the overall heat-insulation property was enhanced. Finally,
      since the IR-reflecting property is provided by the HGM coating, if the coating
      is fouled, the reflectivity decreases. Therefore, with the superhydrophobic
      coating, the surface is protected from fouling, and its lifetime is also
      prolonged.

PMID- 28518102
TI  - NMR Spectroscopy as a Robust Tool for the Rapid Evaluation of the Lipid Profile
      of Fish Oil Supplements.
AB  - The western diet is poor in n-3 fatty acids, therefore the consumption of fish
      oil supplements is recommended to increase the intake of these essential
      nutrients. The objective of this work is to demonstrate the qualitative and
      quantitative analysis of encapsulated fish oil supplements using high-resolution
      1H and 13C NMR spectroscopy utilizing two different NMR instruments; a 500 MHz
      and an 850 MHz instrument. Both proton (1H) and carbon (13C) NMR spectra can be
      used for the quantitative determination of the major constituents of fish oil
      supplements. Quantification of the lipids in fish oil supplements is achieved
      through integration of the appropriate NMR signals in the relevant 1D spectra.
      Results obtained by 1H and 13C NMR are in good agreement with each other, despite
      the difference in resolution and sensitivity between the two nuclei and the two
      instruments. 1H NMR offers a more rapid analysis compared to 13C NMR, as the
      spectrum can be recorded in less than 1 min, in contrast to 13C NMR analysis,
      which lasts from 10 min to one hour. The 13C NMR spectrum, however, is much more
      informative. It can provide quantitative data for a greater number of individual
      fatty acids and can be used for determining the positional distribution of fatty
      acids on the glycerol backbone. Both nuclei can provide quantitative information
      in just one experiment without the need of purification or separation steps. The
      strength of the magnetic field mostly affects the 1H NMR spectra due to its lower
      resolution with respect to 13C NMR, however, even lower cost NMR instruments can
      be efficiently applied as a standard method by the food industry and quality
      control laboratories.

PMID- 28518101
TI  - Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases
      Coordination between Irregular Cerebral and Cardiac Activities.
AB  - In both the East and West, traditional teachings say that the mind and heart are
      somehow closely correlated, especially during spiritual practice. One difficulty
      in proving this objectively is that the natures of brain and heart activities are
      quite different. In this paper, we propose a methodology that uses wavelet
      entropy to measure the chaotic levels of both electroencephalogram (EEG) and
      electrocardiogram (ECG) data and show how this may be used to explore the
      potential coordination between the mind and heart under different experimental
      conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to
      identify the brain regions in which the EEG wavelet entropy was the most affected
      by the experimental conditions. As an illustration, the EEG and ECG were recorded
      under two different conditions (normal rest and mindful breathing) at the
      beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR)
      training course (pretest) and after the course (posttest). Using the proposed
      method, the results consistently showed that the wavelet entropy of the brain EEG
      decreased during the MBSR mindful breathing state as compared to that during the
      closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was
      found during MBSR mindful breathing. However, no difference in wavelet entropy
      during MBSR mindful breathing was found between the pretest and posttest. No
      correlation was observed between the entropy of brain waves and the entropy of
      heartrate during normal rest in all participants, whereas a significant
      correlation was observed during MBSR mindful breathing. Additionally, the most
      well-correlated brain regions were located in the central areas of the brain.
      This study provides a methodology for the establishment of evidence that
      mindfulness practice (i.e., mindful breathing) may increase the coordination
      between mind and heart activities.

PMID- 28518103
TI  - Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase
      mediated Cassette Exchange.
AB  - Gene engineering in mouse embryos or embryonic stem cells (mESCs) allows for the
      study of the function of a given protein. Proteins are the workhorses of the cell
      and often consist of multiple functional domains, which can be influenced by
      posttranslational modifications. The depletion of the entire protein in
      conditional or constitutive knock-out (KO) mice does not take into account this
      functional diversity and regulation. An mESC line and a derived mouse model, in
      which a docking site for FLPe recombination-mediated cassette exchange (RMCE) was
      inserted within the ROSA26 (R26) locus, was previously reported. Here, we report
      on a structure-function approach that allows for molecular dissection of the
      different functionalities of a multidomain protein. To this end, RMCE-compatible
      mice must be crossed with KO mice and then RMCE-compatible KO mESCs must be
      isolated. Next, a panel of putative rescue constructs can be introduced into the
      R26 locus via RMCE targeting. The candidate rescue cDNAs can be easily inserted
      between RMCE sites of the targeting vector using recombination cloning. Next, KO
      mESCs are transfected with the targeting vector in combination with an FLPe
      recombinase expression plasmid. RMCE reactivates the promoter-less neomycin
      resistance gene in the ROSA26 docking sites and allows for the selection of the
      correct targeting event. In this way, high targeting efficiencies close to 100%
      are obtained, allowing for insertion of multiple putative rescue constructs in a
      semi-high throughput manner. Finally, a multitude of R26-driven rescue constructs
      can be tested for their ability to rescue the phenotype that was observed in
      parental KO mESCs. We present a proof-of-principle structure-function study in
      p120 catenin (p120ctn) KO mESCs using endoderm differentiation in embryoid bodies
      (EBs) as the phenotypic readout. This approach enables the identification of
      important domains, putative downstream pathways, and disease-relevant point
      mutations that underlie KO phenotypes for a given protein.

PMID- 28518104
TI  - Neurodevelopmental Reflex Testing in Neonatal Rat Pups.
AB  - Neurodevelopmental reflex testing is commonly used in clinical practice to assess
      the maturation of the nervous system. Neurodevelopmental reflexes are also
      referred to as primitive reflexes. They are sensitive and consistent with later
      outcomes. Abnormal reflexes are described as an absence, persistence,
      reappearance, or latency of reflexes, which are predictive indices of infants
      that are at high risk for neurodevelopmental disorders. Animal models of
      neurodevelopmental disabilities, such as cerebral palsy, often display aberrant
      developmental reflexes, as would be observed in human infants. The techniques
      described assess a variety of neurodevelopmental reflexes in neonatal rats.
      Neurodevelopmental reflex testing offers the investigator a testing method that
      is not otherwise available in such young animals. The methodology presented here
      aims to assist investigators in examining developmental milestones in neonatal
      rats as a method of detecting early-onset brain injury and/or determining the
      effectiveness of therapeutic interventions. The methodology presented here aims
      to provide a general guideline for investigators.

PMID- 28518106
TI  - Isolation of Murine Adipose Tissue-derived Microvascular Fragments as
      Vascularization Units for Tissue Engineering.
AB  - A functional microvascular network is of pivotal importance for the survival and
      integration of engineered tissue constructs. For this purpose, several angiogenic
      and prevascularization strategies have been established. However, most cell-based
      approaches include time-consuming in vitro steps for the formation of a
      microvascular network. Hence, they are not suitable for intraoperative one-step
      procedures. Adipose tissue-derived microvascular fragments (ad-MVF) represent
      promising vascularization units. They can be easily isolated from fat tissue and
      exhibit a functional microvessel morphology. Moreover, they rapidly reassemble
      into new microvascular networks after in vivo implantation. In addition, ad-MVF
      have been shown to induce lymphangiogenesis. Finally, they are a rich source of
      mesenchymal stem cells, which may further contribute to their high
      vascularization potential. In previous studies we have demonstrated the
      remarkable vascularization capacity of ad-MVF in engineered bone and skin
      substitutes. In the present study, we report on a standardized protocol for the
      enzymatic isolation of ad-MVF from murine fat tissue.

PMID- 28518107
TI  - A Large Lateral Craniotomy Procedure for Mesoscale Wide-field Optical Imaging of
      Brain Activity.
AB  - The craniotomy is a commonly performed procedure to expose the brain for in vivo
      experiments. In mouse research, most labs utilize a small craniotomy, typically 3
      mm x 3 mm. This protocol introduces a method for creating a substantially larger
      7 mm x 6 mm cranial window exposing most of a cerebral hemisphere over the mouse
      temporal and parietal cortices (e.g., bregma 2.5 - 4.5 mm, lateral 0 - 6 mm). To
      perform this surgery, the head must be tilted approximately 30 degrees  and much
      of the temporal muscle must be retracted. Due to the large amount of bone
      removal, this procedure is intended only for acute experiments with the animal
      anesthetized throughout the surgery and experiment. The main advantage of this
      innovative large lateral cranial window is to provide simultaneous access to both
      medial and lateral areas of the cortex. This large unilateral cranial window can
      be used to study the neural dynamics between cells, as well as between different
      cortical areas by combining multi-electrode electrophysiological recordings,
      imaging of neuronal activity (e.g., intrinsic or extrinsic imaging), and
      optogenetic stimulation. Additionally, this large craniotomy also exposes a large
      area of cortical blood vessels, allowing for direct manipulation of the lateral
      cortical vasculature.

PMID- 28518105
TI  - Murine Lymphocyte Labeling by 64Cu-Antibody Receptor Targeting for In Vivo Cell
      Trafficking by PET/CT.
AB  - This protocol illustrates the production of 64Cu and the chelator
      conjugation/radiolabeling of a monoclonal antibody (mAb) followed by murine
      lymphocyte cell culture and 64Cu-antibody receptor targeting of the cells. In
      vitro evaluation of the radiolabel and non-invasive in vivo cell tracking in an
      animal model of an airway delayed-type hypersensitivity reaction (DTHR) by PET/CT
      are described. In detail, the conjugation of a mAb with the chelator 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is shown. Following the
      production of radioactive 64Cu, radiolabeling of the DOTA-conjugated mAb is
      described. Next, the expansion of chicken ovalbumin (cOVA)-specific CD4+
      interferon (IFN)-gamma-producing T helper cells (cOVA-TH1) and the subsequent
      radiolabeling of the cOVA-TH1 cells are depicted. Various in vitro techniques are
      presented to evaluate the effects of 64Cu-radiolabeling on the cells, such as the
      determination of cell viability by trypan blue exclusion, the staining for
      apoptosis with Annexin V for flow cytometry, and the assessment of functionality
      by IFN-gamma enzyme-linked immunosorbent assay (ELISA). Furthermore, the
      determination of the radioactive uptake into the cells and the labeling stability
      are described in detail. This protocol further describes how to perform cell
      tracking studies in an animal model for an airway DTHR and, therefore, the
      induction of cOVA-induced acute airway DHTR in BALB/c mice is included. Finally,
      a robust PET/CT workflow including image acquisition, reconstruction, and
      analysis is presented. The 64Cu-antibody receptor targeting approach with
      subsequent receptor internalization provides high specificity and stability,
      reduced cellular toxicity, and low efflux rates compared to common PET-tracers
      for cell labeling, e.g.64Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (64Cu
      PTSM). Finally, our approach enables non-invasive in vivo cell tracking by PET/CT
      with an optimal signal-to-background ratio for 48 h. This experimental approach
      can be transferred to different animal models and cell types with membrane-bound
      receptors that are internalized.

PMID- 28518108
TI  - Identification of Plant Ice-binding Proteins Through Assessment of Ice
      recrystallization Inhibition and Isolation Using Ice-affinity Purification.
AB  - Ice-binding proteins (IBPs) belong to a family of stress-induced proteins that
      are synthesized by certain organisms exposed to subzero temperatures. In plants,
      freeze damage occurs when extracellular ice crystals grow, resulting in the
      rupture of plasma membranes and possible cell death. Adsorption of IBPs to ice
      crystals restricts further growth by a process known as ice-recrystallization
      inhibition (IRI), thereby reducing cellular damage. IBPs also demonstrate the
      ability to depress the freezing point of a solution below the equilibrium melting
      point, a property known as thermal hysteresis (TH) activity. These protective
      properties have raised interest in the identification of novel IBPs due to their
      potential use in industrial, medical and agricultural applications. This paper
      describes the identification of plant IBPs through 1) the induction and
      extraction of IBPs in plant tissue, 2) the screening of extracts for IRI
      activity, and 3) the isolation and purification of IBPs. Following the induction
      of IBPs by low temperature exposure, extracts are tested for IRI activity using a
      'splat assay', which allows the observation of ice crystal growth using a
      standard light microscope. This assay requires a low protein concentration and
      generates results that are quickly obtained and easily interpreted, providing an
      initial screen for ice binding activity. IBPs can then be isolated from
      contaminating proteins by utilizing the property of IBPs to adsorb to ice,
      through a technique called 'ice-affinity purification'. Using cell lysates
      collected from plant extracts, an ice hemisphere can be slowly grown on a brass
      probe. This incorporates IBPs into the crystalline structure of the
      polycrystalline ice. Requiring no a priori biochemical or structural knowledge of
      the IBP, this method allows for recovery of active protein. Ice-purified protein
      fractions can be used for downstream applications including the identification of
      peptide sequences by mass spectrometry and the biochemical analysis of native
      proteins.

PMID- 28518109
TI  - Assessment of Neuronal Viability Using Fluorescein Diacetate-Propidium Iodide
      Double Staining in Cerebellar Granule Neuron Culture.
AB  - Primary cultured Cerebellar Granule Neurons (CGNs) have been widely used as an in
      vitro model in neuroscience and neuropharmacology research. However, the co
      existence of glial cells and neurons in CGN culture might lead to biases in the
      accurate assessment of neuronal viability. Fluorescein diacetate (FDA) and
      Propidium Iodide (PI) double staining has been used to measure cell viability by
      simultaneously evaluating the viable and dead cells. We used FDA-PI double
      staining to improve the sensitivities of the colorimetric assays and to evaluate
      neuronal viability in CGNs. Furthermore, we added blue fluorescent DNA stains
      (e.g., Hoechst) to improve the accuracy. This protocol describes how to improve
      the accuracy of assessment of neuronal viability by using these methods in CGN
      culture. Using this protocol, the number of glial cells can be excluded by using
      fluorescence microscopy. A similar strategy can be applied to distinguish the
      unwanted glial cells from neurons in various mixed cell cultures, such as primary
      cortical culture and hippocampal culture.

PMID- 28518110
TI  - External Excitation of Neurons Using Electric and Magnetic Fields in One- and Two
      dimensional Cultures.
AB  - A neuron will fire an action potential when its membrane potential exceeds a
      certain threshold. In typical activity of the brain, this occurs as a result of
      chemical inputs to its synapses. However, neurons can also be excited by an
      imposed electric field. In particular, recent clinical applications activate
      neurons by creating an electric field externally. It is therefore of interest to
      investigate how the neuron responds to the external field and what causes the
      action potential. Fortunately, precise and controlled application of an external
      electric field is possible for embryonic neuronal cells that are excised,
      dissociated and grown in cultures. This allows the investigation of these
      questions in a highly reproducible system. In this paper some of the techniques
      used for controlled application of external electric field on neuronal cultures
      are reviewed. The networks can be either one dimensional, i.e. patterned in
      linear forms or allowed to grow on the whole plane of the substrate, and thus two
      dimensional. Furthermore, the excitation can be created by the direct application
      of electric field via electrodes immersed in the fluid (bath electrodes) or by
      inducing the electric field using the remote creation of magnetic pulses.

PMID- 28518111
TI  - Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in
      Alzheimer's Mouse Models.
AB  - Neurotransmitter disruption is often a key component of diseases of the central
      nervous system (CNS), playing a role in the pathology underlying Alzheimer's
      disease, Parkinson's disease, depression, and anxiety. Traditionally,
      microdialysis has been the most common (lauded) technique to examine
      neurotransmitter changes that occur in these disorders. But because microdialysis
      has the ability to measure slow 1-20 minute changes across large areas of tissue,
      it has the disadvantage of invasiveness, potentially destroying intrinsic
      connections within the brain and a slow sampling capability. A relatively newer
      technique, the microelectrode array (MEA), has numerous advantages for measuring
      specific neurotransmitter changes within discrete brain regions as they occur,
      making for a spatially and temporally precise approach. In addition, using MEAs
      is minimally invasive, allowing for measurement of neurotransmitter alterations
      in vivo. In our laboratory, we have been specifically interested in changes in
      the neurotransmitter, glutamate, related to Alzheimer's disease pathology. As
      such, the method described here has been used to assess potential hippocampal
      disruptions in glutamate in a transgenic mouse model of Alzheimer's disease.
      Briefly, the method used involves coating a multi-site microelectrode with an
      enzyme very selective for the neurotransmitter of interest and using self
      referencing sites to subtract out background noise and interferents. After
      plating and calibration, the MEA can be constructed with a micropipette and
      lowered into the brain region of interest using a stereotaxic device. Here, the
      method described involves anesthetizing rTg(TauP301L)4510 mice and using a
      stereotaxic device to precisely target sub-regions (DG, CA1, and CA3) of the
      hippocampus.

PMID- 28518112
TI  - Functional Manipulation of Maternal Gene Products Using In Vitro Oocyte
      Maturation in Zebrafish.
AB  - Cellular events that take place during the earliest stages of animal embryonic
      development are driven by maternally derived gene products deposited into the
      developing oocyte. Because these events rely on maternal products which typically
      act very soon after fertilization-that preexist inside the egg, standard
      approaches for expression and functional reduction involving the injection of
      reagents into the fertilized egg are typically ineffective. Instead, such
      manipulations must be performed during oogenesis, prior to or during the
      accumulation of maternal products. This article describes in detail a protocol
      for the in vitro maturation of immature zebrafish oocytes and their subsequent in
      vitro fertilization, yielding viable embryos that survive to adulthood. This
      method allows the functional manipulation of maternal products during oogenesis,
      such as the expression of products for phenotypic rescue and tagged construct
      visualization, as well as the reduction of gene function through reverse-genetics
      agents.

PMID- 28518113
TI  - Enhanced Sample Multiplexing of Tissues Using Combined Precursor Isotopic
      Labeling and Isobaric Tagging (cPILOT).
AB  - There is an increasing demand to analyze many biological samples for disease
      understanding and biomarker discovery. Quantitative proteomics strategies that
      allow simultaneous measurement of multiple samples have become widespread and
      greatly reduce experimental costs and times. Our laboratory developed a technique
      called combined precursor isotopic labeling and isobaric tagging (cPILOT), which
      enhances sample multiplexing of traditional isotopic labeling or isobaric tagging
      approaches. Global cPILOT can be applied to samples originating from cells,
      tissues, bodily fluids, or whole organisms and gives information on relative
      protein abundances across different sample conditions. cPILOT works by 1) using
      low pH buffer conditions to selectively dimethylate peptide N-termini and 2)
      using high pH buffer conditions to label primary amines of lysine residues with
      commercially-available isobaric reagents (see Table of Materials/Reagents). The
      degree of sample multiplexing available is dependent on the number of precursor
      labels used and the isobaric tagging reagent. Here, we present a 12-plex analysis
      using light and heavy dimethylation combined with six-plex isobaric reagents to
      analyze 12 samples from mouse tissues in a single analysis. Enhanced multiplexing
      is helpful for reducing experimental time and cost and more importantly, allowing
      comparison across many sample conditions (biological replicates, disease stage,
      drug treatments, genotypes, or longitudinal time-points) with less experimental
      bias and error. In this work, the global cPILOT approach is used to analyze
      brain, heart, and liver tissues across biological replicates from an Alzheimer's
      disease mouse model and wild-type controls. Global cPILOT can be applied to study
      other biological processes and adapted to increase sample multiplexing to greater
      than 20 samples.

PMID- 28518115
TI  - Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem
      Cells in Two and Three-dimensional Embryoid Bodies.
AB  - Mouse embryonic stem cells (ESCs) isolated from the inner mass of the blastocyst
      (typically at day E3.5), can be used as in vitro model system for studying early
      embryonic development. In the absence of leukemia inhibitory factor (LIF), ESCs
      differentiate by default into neural precursor cells. They can be amassed into a
      three dimensional (3D) spherical aggregate termed embryoid body (EB) due to its
      similarity to the early stage embryo. EBs can be seeded on fibronectin-coated
      coverslips, where they expand by growing two dimensional (2D) extensions, or
      implanted in 3D collagen matrices where they continue growing as spheroids, and
      differentiate into the three germ layers: endodermal, mesodermal, and ectodermal.
      The 3D collagen culture mimics the in vivo environment more closely than the 2D
      EBs. The 2D EB culture facilitates analysis by immunofluorescence and
      immunoblotting to track differentiation. We have developed a two-step neural
      differentiation protocol. In the first step, EBs are generated by the hanging
      drop technique, and, simultaneously, are induced to differentiate by exposure to
      retinoic acid (RA). In the second step, neural differentiation proceeds in a 2D
      or 3D format in the absence of RA.

PMID- 28518114
TI  - Preparation and In Vitro Characterization of Magnetized miR-modified Endothelial
      Cells.
AB  - To date, the available surgical and pharmacological treatments for cardiovascular
      diseases (CVD) are limited and often palliative. At the same time, gene and cell
      therapies are highly promising alternative approaches for CVD treatment. However,
      the broad clinical application of gene therapy is greatly limited by the lack of
      suitable gene delivery systems. The development of appropriate gene delivery
      vectors can provide a solution to current challenges in cell therapy. In
      particular, existing drawbacks, such as limited efficiency and low cell retention
      in the injured organ, could be overcome by appropriate cell engineering (i.e.,
      genetic) prior to transplantation. The presented protocol describes the efficient
      and safe transient modification of endothelial cells using a polyethyleneimine
      superparamagnetic magnetic nanoparticle (PEI/MNP)-based delivery vector. Also,
      the algorithm and methods for cell characterization are defined. The successful
      intracellular delivery of microRNA (miR) into human umbilical vein endothelial
      cells (HUVECs) has been achieved without affecting cell viability, functionality,
      or intercellular communication. Moreover, this approach was proven to cause a
      strong functional effect in introduced exogenous miR. Importantly, the
      application of this MNP-based vector ensures cell magnetization, with
      accompanying possibilities of magnetic targeting and non-invasive MRI tracing.
      This may provide a basis for magnetically guided, genetically engineered cell
      therapeutics that can be monitored non-invasively with MRI.

PMID- 28518116
TI  - The WinCF Model - An Inexpensive and Tractable Microcosm of a Mucus Plugged
      Bronchiole to Study the Microbiology of Lung Infections.
AB  - Many chronic airway diseases result in mucus plugging of the airways. Lungs of an
      individual with cystic fibrosis are an exemplary case where their mucus-plugged
      bronchioles create a favorable habitat for microbial colonization. Various
      pathogens thrive in this environment interacting with each other and driving many
      of the symptoms associated with CF disease. Like any microbial community, the
      chemical conditions of their habitat have a significant impact on the community
      structure and dynamics. For example, different microorganisms thrive in differing
      levels of oxygen or other solute concentrations. This is also true in the CF
      lung, where oxygen concentrations are believed to drive community physiology and
      structure. The methods described here are designed to mimic the lung environment
      and grow pathogens in a manner more similar to that from which they cause
      disease. Manipulation of the chemical surroundings of these microbes is then used
      to study how the chemistry of lung infections governs its microbial ecology. The
      method, called the WinCF system, is based on artificial sputum medium and narrow
      capillary tubes meant to provide an oxygen gradient similar to that which exists
      in mucus-plugged bronchioles. Manipulating chemical conditions, such as the media
      pH of the sputum or antibiotics pressure, allows for visualization of the
      microbiological differences in those samples using colored indicators, watching
      for gas or biofilm production, or extracting and sequencing the nucleic acid
      contents of each sample.

PMID- 28518117
TI  - Simultaneous Evaluation of Cerebral Hemodynamics and Light Scattering Properties
      of the In Vivo Rat Brain Using Multispectral Diffuse Reflectance Imaging.
AB  - The simultaneous evaluation of cerebral hemodynamics and the light scattering
      properties of in vivo rat brain tissue is demonstrated using a conventional
      multispectral diffuse reflectance imaging system. This system is constructed from
      a broadband white light source, a motorized filter wheel with a set of narrowband
      interference filters, a light guide, a collecting lens, a video zoom lens, and a
      monochromatic charged-coupled device (CCD) camera. An ellipsoidal cranial window
      is made in the skull bone of a rat under isoflurane anesthesia to capture in vivo
      multispectral diffuse reflectance images of the cortical surface. Regulation of
      the fraction of inspired oxygen using a gas mixture device enables the induction
      of different respiratory states such as normoxia, hyperoxia, and anoxia. A Monte
      Carlo simulation-based multiple regression analysis for the measured
      multispectral diffuse reflectance images at nine wavelengths (500, 520, 540, 560,
      570, 580, 600, 730, and 760 nm) is then performed to visualize the two
      dimensional maps of hemodynamics and the light scattering properties of the in
      vivo rat brain.

PMID- 28518118
TI  - Harnessing the DNA Dye-triggered Side Population Phenotype to Detect and Purify
      Cancer Stem Cells from Biological Samples.
AB  - Cancer is a stem cell-driven disease and eradication of these cells has become a
      major therapeutic goal. Deciphering vulnerabilities of Cancer Stem Cells (CSCs)
      and identifying suitable molecular targets relies on methods that allow their
      specific discrimination in heterogeneous samples such as cell lines and ex vivo
      tumor tissue. Flow cytometry/FACS is a powerful technology to multi
      parametrically dissect biological samples at the single cell level and is to date
      the method of choice to recover live cells for downstream analyses. Surface
      markers such as CD44 and CD133 as well as detection of aldehyde dehydrogenase
      enzymatic activity have often been used to define and sort out CSCs from tumor
      samples by FACS. A complementary approach, depicted here in methodological
      detail, makes use of functional dye extrusion by ABC drug transporters, which
      identifies a distinct population of fluorescence-dim cells commonly referred to
      as side population (SP). SP cancer cells exhibit canonical stem cell
      characteristics and can be abrogated and functionally confirmed using agents that
      inhibit the dye-extruding drug transporter (most frequently ABCB1/P
      glycoprotein/MDR1/CD243 and ABCG2/Bcrp1/CD338). Moreover, the SP assay is
      compatible with other flow cytometric evaluations such as staining of surface
      antigens, aldehyde dehydrogenase detection and dead cell discrimination (e.g.,
      with 7-AAD or propidium iodide (PI)). Thus, we describe a valuable and broadly
      applicable method for CSC identification, isolation and sub-characterization
      mechanistically based on a functional, rather than a phenotypic parameter.
      Although originally performed with Hoechst 33342 as triggering dye, we here focus
      on the more recent Violet dye-based SP phenotype that is resolvable on any flow
      cytometer equipped with a violet laser source.

PMID- 28518119
TI  - Analysis of Cell Suspensions Isolated from Solid Tissues by Spectral Flow
      Cytometry.
AB  - Flow cytometry has been used for the past 40 years to define and analyze the
      phenotype of lymphoid and other hematopoietic cells. Initially restricted to the
      analysis of a few fluorochromes, currently there are dozens of different
      fluorescent dyes, and up to 14-18 different dyes can be combined at a time.
      However, several limitations still impair the analytical capabilities. Because of
      the multiplicity of fluorescent probes, data analysis has become increasingly
      complex due to the need of large, multi-parametric compensation matrices.
      Moreover, mutant mouse models carrying fluorescent proteins to detect and trace
      specific cell types in different tissues have become available, so the analysis
      (by flow cytometry) of auto-fluorescent cell suspensions obtained from solid
      organs is required. Spectral flow cytometry, which distinguishes the shapes of
      emission spectra along a wide range of continuous wavelengths, addresses some of
      these problems. The data is analyzed with an algorithm that replaces compensation
      matrices and treats auto-fluorescence as an independent parameter. Thus, spectral
      flow cytometry should be capable of discriminating fluorochromes with similar
      emission peaks and can provide a multi-parametric analysis without compensation
      requirements. This protocol describes the spectral flow cytometry analysis,
      allowing for a 21-parameter (19 fluorescent probes) characterization and the
      management of an auto-fluorescent signal, providing high resolution in minor
      population detection. The results presented here show that spectral flow
      cytometry presents advantages in the analysis of cell populations from tissues
      difficult to characterize in conventional flow cytometry, such as the heart and
      the intestine. Spectral flow cytometry thus demonstrates the multi-parametric
      analytical capacity of high-performing conventional flow cytometry without the
      requirement for compensation and enables auto-fluorescence management.

PMID- 28518120
TI  - Ligand Nano-cluster Arrays in a Supported Lipid Bilayer.
AB  - Currently there is considerable interest in creating ordered arrays of adhesive
      protein islands in a sea of passivated surface for cell biological studies. In
      the past years, it has become increasingly clear that living cells respond, not
      only to the biochemical nature of the molecules presented to them but also to the
      way these molecules are presented. Creating protein micro-patterns is therefore
      now standard in many biology laboratories; nano-patterns are also more
      accessible. However, in the context of cell-cell interactions, there is a need to
      pattern not only proteins but also lipid bilayers. Such dual proteo-lipidic
      patterning has so far not been easily accessible. We offer a facile technique to
      create protein nano-dots supported on glass and propose a method to backfill the
      inter-dot space with a supported lipid bilayer (SLB). From photo-bleaching of
      tracer fluorescent lipids included in the SLB, we demonstrate that the bilayer
      exhibits considerable in-plane fluidity. Functionalizing the protein dots with
      fluorescent groups allows us to image them and to show that they are ordered in a
      regular hexagonal lattice. The typical dot size is about 800 nm and the spacing
      demonstrated here is 2 microns. These substrates are expected to serve as useful
      platforms for cell adhesion, migration and mechano-sensing studies.

PMID- 28518122
TI  - Dorsal Root Ganglion Injection and Dorsal Root Crush Injury as a Model for
      Sensory Axon Regeneration.
AB  - Achieving axon regeneration after nervous system injury is a challenging task. As
      different parts of the central nervous system (CNS) differ from each other
      anatomically, it is important to identify an appropriate model to use for the
      study of axon regeneration. By using a suitable model, we can formulate a
      specific treatment based on the severity of injury, the neuronal cell type of
      interest, and the desired spinal tract for assessing regeneration. Within the
      sensory pathway, DRG neurons are responsible for relaying sensory information
      from the periphery to the CNS. We present here a protocol that uses a DRG
      injection with a viral vector and a concurrent dorsal root crush injury in the
      lower cervical spinal cord of an adult rat as a model to study sensory axon
      regeneration. As demonstrated using a control virus, AAV5-GFP, we show the
      effectiveness of a direct DRG injection in transducing DRG neurons and tracing
      sensory axons into the spinal cord. We also show the effectiveness of the dorsal
      root crush injury in denervating the forepaw as an injury model for evaluating
      axon regeneration. Despite the requirement for specialized training to perform
      this invasive surgical procedure, the protocol is flexible, and potential users
      can modify many parts to accommodate their experimental requirements.
      Importantly, it can serve as a foundation for those in search of a suitable
      animal model for their studies. We believe that this article will help new users
      to learn the procedure in a very efficient and effective manner.

PMID- 28518121
TI  - Two Algorithms for High-throughput and Multi-parametric Quantification of
      Drosophila Neuromuscular Junction Morphology.
AB  - Synaptic morphology is tightly related to synaptic efficacy, and in many cases
      morphological synapse defects ultimately lead to synaptic malfunction. The
      Drosophila larval neuromuscular junction (NMJ), a well-established model for
      glutamatergic synapses, has been extensively studied for decades. Identification
      of mutations causing NMJ morphological defects revealed a repertoire of genes
      that regulate synapse development and function. Many of these were identified in
      large-scale studies that focused on qualitative approaches to detect
      morphological abnormalities of the Drosophila NMJ. A drawback of qualitative
      analyses is that many subtle players contributing to NMJ morphology likely remain
      unnoticed. Whereas quantitative analyses are required to detect the subtler
      morphological differences, such analyses are not yet commonly performed because
      they are laborious. This protocol describes in detail two image analysis
      algorithms "Drosophila NMJ Morphometrics" and "Drosophila NMJ Bouton
      Morphometrics", available as Fiji-compatible macros, for quantitative, accurate
      and objective morphometric analysis of the Drosophila NMJ. This methodology is
      developed to analyze NMJ terminals immunolabeled with the commonly used markers
      Dlg-1 and Brp. Additionally, its wider application to other markers such as Hrp,
      Csp and Syt is presented in this protocol. The macros are able to assess nine
      morphological NMJ features: NMJ area, NMJ perimeter, number of boutons, NMJ
      length, NMJ longest branch length, number of islands, number of branches, number
      of branching points and number of active zones in the NMJ terminal.

PMID- 28518123
TI  - Expression of Exogenous Cytokine in Patient-derived Xenografts via Injection with
      a Cytokine-transduced Stromal Cell Line.
AB  - Patient-derived xenograft (PDX) mice are produced by transplanting human cells
      into immune deficient mice. These models are an important tool for studying the
      mechanisms of normal and malignant hematopoiesis and are the gold standard for
      identifying effective chemotherapies for many malignancies. PDX models are
      possible because many of the mouse cytokines also act on human cells. However,
      this is not the case for all cytokines, including many that are critical for
      studying normal and malignant hematopoiesis in human cells. Techniques that
      engineer mice to produce human cytokines (transgenic and knock-in models) require
      significant expense before the usefulness of the model has been demonstrated.
      Other techniques are labor intensive (injection of recombinant cytokine or
      lentivirus) and in some cases require high levels of technical expertise
      (hydrodynamic injection of DNA). This report describes a simple method for
      generating PDX mice that have exogenous human cytokine (TSLP, thymic stromal
      lymphopoietin) via weekly intraperitoneal injection of stroma that have been
      transduced to overexpress this cytokine. Use of this method provides an in vivo
      source of continuous cytokine production that achieves physiological levels of
      circulating human cytokine in the mouse. Plasma levels of human cytokine can be
      varied based on the number of stromal cells injected, and cytokine production can
      be initiated at any point in the experiment. This method also includes cytokine
      negative control mice that are similarly produced, but through intraperitoneal
      injection of stroma transduced with a control vector. We have previously
      demonstrated that leukemia cells harvested from TSLP-expressing PDX, as compared
      to control PDX, exhibit a gene expression pattern more like the original patient
      sample. Together the cytokine-producing and cytokine-negative PDX mice produced
      by this method provide a model system that we have used successfully to study the
      role of TSLP in normal and malignant hematopoiesis.

PMID- 28518124
TI  - Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with
      Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA).
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital anomaly which is one of leading causes of myocardial
      ischemia and infarction in children. If left untreated, it results in a 90%
      mortality rate in the first year of life. In patients who survive to the
      adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow
      provide a substrate for chronic subendocardial ischemia, which may lead to left
      ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular
      arrhythmias, and sudden cardiac death. The average age of life-threatening
      presentation is 33 years and of sudden cardiac death 31 years. Therefore,
      surgical correction is highly recommended as soon as the diagnosis is made,
      regardless of age. In adult-type ALCAPA originating from the right-facing sinus
      of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is
      the more physiologically sound repair technique to re-establish the dual-coronary
      perfusion system and is recommended. This protocol describes the technique of
      direct re-implantation of adult-type ALCAPA into the aorta.

PMID- 28518125
TI  - Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide
      Analysis Using Mass Spectrometry.
AB  - Fibrosis is a hallmark of many cardiovascular diseases and is associated with the
      exacerbated secretion and deposition of the extracellular matrix (ECM). Using
      proteomics, we have previously identified more than 150 ECM and ECM-associated
      proteins in cardiovascular tissues. Notably, many ECM proteins are glycosylated.
      This post-translational modification affects protein folding, solubility,
      binding, and degradation. We have developed a sequential extraction and
      enrichment method for ECM proteins that is compatible with the subsequent liquid
      chromatography tandem mass spectrometry (LC-MS/MS) analysis of intact
      glycopeptides. The strategy is based on sequential incubations with NaCl, SDS for
      tissue decellularization, and guanidine hydrochloride for the solubilization of
      ECM proteins. Recent advances in LC-MS/MS include fragmentation methods, such as
      combinations of higher-energy collision dissociation (HCD) and electron transfer
      dissociation (ETD), which allow for the direct compositional analysis of
      glycopeptides of ECM proteins. In the present paper, we describe a method to
      prepare the ECM from tissue samples. The method not only allows for protein
      profiling but also the assessment and characterization of glycosylation by MS
      analysis.

PMID- 28518126
TI  - Techniques to Induce and Quantify Cellular Senescence.
AB  - In response to cellular stress or damage, proliferating cells can induce a
      specific program that initiates a state of long-term cell-cycle arrest, termed
      cellular senescence. Accumulation of senescent cells occurs with organismal aging
      and through continual culturing in vitro. Senescent cells influence many
      biological processes, including embryonic development, tissue repair and
      regeneration, tumor suppression, and aging. Hallmarks of senescent cells include,
      but are not limited to, increased senescence-associated beta-galactosidase
      activity (SA-beta-gal); p16INK4A, p53, and p21 levels; higher levels of DNA
      damage, including gamma-H2AX; the formation of Senescence-associated
      Heterochromatin Foci (SAHF); and the acquisition of a Senescence-associated
      Secretory Phenotype (SASP), a phenomenon characterized by the secretion of a
      number of pro-inflammatory cytokines and signaling molecules. Here, we describe
      protocols for both replicative and DNA damage-induced senescence in cultured
      cells. In addition, we highlight techniques to monitor the senescent phenotype
      using several senescence-associated markers, including SA-beta-gal, gamma-H2AX
      and SAHF staining, and to quantify protein and mRNA levels of cell cycle
      regulators and SASP factors. These methods can be applied to the assessment of
      senescence in various models and tissues.

PMID- 28518127
TI  - Plunge Freezing: A Tool for the Ultrastructural and Immunolocalization Studies of
      Suspension Cells in Transmission Electron Microscopy.
AB  - Transmission Electron Microscopy (TEM) is an extraordinary tool for studying cell
      ultrastructure, in order to localize proteins and visualize macromolecular
      complexes at very high resolution. However, to get as close as possible to the
      native state, perfect sample preservation is required. Conventional electron
      microscopy (EM) fixation with aldehydes, for instance, does not provide good
      ultrastructural preservation. The slow penetration of fixatives induces cell
      reorganization and loss of various cell components. Therefore, conventional EM
      fixation does not allow for an instantaneous stabilization and preservation of
      structures and antigenicity. The best choice for examining intracellular events
      is to use cryofixation followed by the freeze-substitution fixation method that
      keeps cells in their native state. High-pressure freezing/freeze-substitution,
      which preserves the integrity of cellular ultrastructure, is the most commonly
      used method, but requires expensive equipment. Here, an easy-to-use and low-cost
      freeze fixation method followed by freeze-substitution for suspension cell
      cultures is presented.

PMID- 28518128
TI  - An In Vitro Caseum Binding Assay that Predicts Drug Penetration in Tuberculosis
      Lesions.
AB  - The eradication of tuberculosis disease requires drug regimens that can penetrate
      the multiple layers of complex pulmonary lesions. Drug distribution in the
      caseous cores of cavities and lesions is especially crucial because they harbor
      subpopulations of drug-tolerant bacteria also commonly referred to as persisters.
      Existing methods for the measurement of drug penetration in tuberculosis lesions
      involve costly and time-consuming in vivo pharmacokinetic studies coupled to
      bioanalytical or imaging techniques. The in vitro measurement of drug binding to
      caseum macromolecules was proposed as an alternative to such techniques since
      this binding hinders the passive diffusion of drug molecules through caseum.
      Rapid equilibrium dialysis is a fast and reliable system for performing plasma
      protein and tissue binding studies. In this protocol, we used a rapid equilibrium
      dialysis (RED) device to measure drug binding to homogenates of caseum that is
      excised from the lesions and cavities of tuberculosis-infected rabbits. The
      protocol also describes how to generate a surrogate matrix from lipid loaded THP
      1 macrophages to use in place of caseum. This caseum/surrogate binding assay is
      an important tool in tuberculosis drug discovery and can be adapted to help study
      drug distribution in lesions or abscesses caused by other diseases.

PMID- 28518129
TI  - Cardiac Muscle Cell-based Actuator and Self-stabilizing Biorobot - Part 2.
AB  - In recent years, hybrid devices that consist of a living cell or tissue component
      integrated with a synthetic mechanical backbone have been developed. These
      devices, called biorobots, are powered solely by the force generated from the
      contractile activity of the living component and, due to their many inherent
      advantages, could be an alternative to conventional fully artificial robots.
      Here, we describe the methods to seed and characterize a biological actuator and
      a biorobot that was designed, fabricated, and functionalized in the first part of
      this two-part article. Fabricated biological actuator and biorobot devices
      composed of a polydimethylsiloxane (PDMS) base and a thin film cantilever were
      functionalized for cell attachment with fibronectin. Following functionalization,
      neonatal rat cardiomyocytes were seeded onto the PDMS cantilever arm at a high
      density, resulting in a confluent cell sheet. The devices were imaged every day
      and the movement of the cantilever arms was analyzed. On the second day after
      seeding, we observed the bending of the cantilever arms due to the forces exerted
      by the cells during spontaneous contractions. Upon quantitative analysis of the
      cantilever bending, a gradual increase in the surface stress exerted by the cells
      as they matured over time was observed. Likewise, we observed movement of the
      biorobot due to the actuation of the PDMS cantilever arm, which acted as a fin.
      Upon quantification of the swimming profiles of the devices, various propulsion
      modes were observed, which were influenced by the resting angle of the fin. The
      direction of motion and the beating frequency were also determined by the resting
      angle of the fin, and a maximum swim velocity of 142 um/s was observed. In this
      manuscript, we describe the procedure for populating the fabricated devices with
      cardiomyocytes, as well as for the assessment of the biological actuator and
      biorobot activity.

PMID- 28518130
TI  - How to Conduct and Interpret Systematic Reviews and Meta-Analyses.
AB  - Systematic reviews with or without meta-analyses serve a key purpose in
      critically and objectively synthesizing all available evidence regarding a
      focused clinical question and can inform clinical practice and clinical
      guidelines. Performing a rigorous systematic review is multi-step process, which
      includes (a) identifying a well-defined focused clinically relevant question, (b)
      developing a detailed review protocol with strict inclusion and exclusion
      criteria, (c) systematic literature search of multiple databases and unpublished
      data, in consultation with a medical librarian, (d) meticulous study
      identification and (e) systematic data abstraction, by at least two sets of
      investigators independently, (f) risk of bias assessment, and (g) thoughtful
      quantitative synthesis through meta-analysis where relevant. Besides informing
      guidelines, credible systematic reviews and quality of evidence assessment can
      help identify key knowledge gaps for future studies.

PMID- 28518133
TI  - An evaluation of hydrocortisone dosing for neonatal refractory hypotension.
AB  - OBJECTIVE: The objective of the study was to compare blood pressure, vasoactive
      medication requirements and adverse outcomes after administration of high- versus
      low-dose hydrocortisone (HC) in preterm infants. STUDY DESIGN: This is a
      retrospective analysis of 106 infants ?28 weeks gestational age with hypotension
      requiring vasoactive infusions and high-dose (4 mg kg-1 per day, n=50), low-dose
      (1 to 3 mg kg-1 per day, n=20) or no HC (n=36) from 2011 to 2015. Groups were
      compared by two-tailed t-test or chi2, and correlation estimated by multivariable
      logistic regression. RESULTS: There were no differences in measured efficacy
      between the low- and high-dose groups. Infants with pre-treatment cortisol >15
      mcg dl-1 who received HC therapy showed less improvement in vasoactive burden,
      increased hyperglycemia (P=0.015) and increased death independent of HC dose
      (odds ratio 26.3, 3.5 to 198.3, P=0.002). CONCLUSION: These results support using
      the lowest effective HC dose in preterm infants. In addition, HC therapy should
      likely be avoided in infants who are not cortisol deficient.

PMID- 28518131
TI  - Incidence of respiratory viral infection in infants with respiratory symptoms
      evaluated for late-onset sepsis.
AB  - OBJECTIVE: To determine the frequency, etiology and impact of respiratory viral
      infection (RVI) on infants evaluated for late-onset sepsis (LOS), defined as
      sepsis occurring >72 h of life, in the neonatal intensive care unit. STUDY
      DESIGN: Prospective observational study conducted from 6 March 2014 to 3 May 2016
      on infants evaluated for LOS. PCR viral panel performed on nasopharyngeal
      specimens among infants with clinical suspicion for RVI. Sequence analysis was
      performed to determine viral subtypes. Fisher's exact or chi2 tests were done to
      determine the impact of RVI. RESULTS: During the 26-month study, there were 357
      blood cultures obtained for LOS evaluations, 29 (8%) had a respiratory virus
      detected. Only 88 (25%) of infants evaluated for LOS also had clinical suspicion
      for a respiratory viral infection. RSV (14 of 29; 48%) was the predominant virus
      detected. Almost all infants (13 of 14; 93%) with RSV required increased
      respiratory support. Antimicrobial therapy was withheld or discontinued on most
      infants with a virus detected (18 of 29; 62%) and in the majority where there was
      no confirmed bacterial co-infection (18 of 20; 90%). CONCLUSION: The incidence of
      RVI in infants being evaluated for LOS is about 8%. RVI should be considered in
      LOS evaluation to prevent unnecessary antibiotic therapy.

PMID- 28518132
TI  - Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal
      endotracheal intubation among pediatric trainees? a randomized controlled study.
AB  - BACKGROUND: To study the impact of videolaryngoscopy (VL) on intubation success
      among pediatric trainees compared with direct laryngoscopy (DL). METHODS: One
      hundred pediatric residents were enrolled in a randomized, crossover, simulation
      study comparing VL to DL. Following a didactic session on neonatal intubation,
      residents intubated a standard neonatal mannequin. Three Neonatal Resuscitation
      Program (NRP) scenarios were then conducted, followed by a mannequin intubation
      with the alternate device. Number of attempts and time to intubation were
      recorded for all intubations. RESULTS: Proportion of successful intubations on
      first attempt was greater with VL compared with DL (88% versus 63%; P=0.008). The
      DL group increased success after crossover with VL (63% versus 89%; P=0.008).
      Exposure to VL also reduced intubation time after device crossover (median
      intubation time: 31 versus 17 s; P=0.048). CONCLUSIONS: VL increased the success
      of endotracheal intubation by pediatric residents in simulation, with skills
      transferrable to DL.

PMID- 28518136
TI  - Corrigendum: Intraventricular injections of mesenchymal stem cells activate
      endogenous functional remyelination in a chronic demyelinating murine model.
AB  - This corrects the article DOI: 10.1038/cddis.2016.130.

PMID- 28518134
TI  - ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through
      activating Ca2+/RhoA pathway.
AB  - Extracellular acid can have important effects on cancer cells. Acid-sensing ion
      channels (ASICs), which emerged as key receptors for extracellular acidic pH, are
      differently expressed during various diseases and have been implicated in
      underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly
      expressed on membrane of pancreatic cancer cells and upregulated in pancreatic
      cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward
      current, which is required for elevation of intracellular Ca2+ concentration
      ([Ca2+]i). Inhibition of ASIC1 and ASIC3 with siRNA or pharmacological inhibitor
      significantly decreased [Ca2+]i and its downstream RhoA during acidity and, thus,
      suppressed acidity-induced epithelial-mesenchymal transition (EMT) of pancreatic
      cancer cells. Meanwhile, downregulating [Ca2+]i with calcium chelating agent
      BAPTA-AM or knockdown of RhoA with siRNA also significantly repressed acidity
      induced EMT of pancreatic cancer cells. Significantly, although without obvious
      effect on proliferation, knockdown of ASIC1 and ASIC3 in pancreatic cancer cells
      significantly suppresses liver and lung metastasis in xenograft model. In
      addition, ASIC1 and ASIC3 are positively correlated with expression of
      mesenchymal marker vimentin, but inversely correlated with epithelial marker E
      cadherin in pancreatic cancer cells. In conclusion, this study indicates that
      ASICs are master regulator of acidity-induced EMT. In addition, the data
      demonstrate a functional link between ASICs and [Ca2+]i/RhoA pathway, which
      contributes to the acidity-induced EMT.

PMID- 28518135
TI  - RACK1 depletion in the ribosome induces selective translation for non-canonical
      autophagy.
AB  - RACK1, which was first demonstrated as a substrate of PKCbeta II, functions as a
      scaffold protein and associates with the 40S small ribosomal subunit. According
      to previous reports, ribosomal RACK1 was also suggested to control translation
      depending on the status in translating ribosome. We here show that RACK1
      knockdown induces autophagy independent of upstream canonical factors such as
      Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown
      induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating
      increased translation of these proteins. Therefore, we propose that the RACK1
      depletion-induced autophagy is distinct from canonical autophagy. Finally, we
      confirm that cells expressing mutant RACK1 (RACK1R36D/K38E) defective in ribosome
      binding showed the same result as RACK1-knockdown cells. Altogether, our data
      clearly show that the depletion of ribosomal RACK1 alters the capacity of the
      ribosome to translate specific mRNAs, resulting in selective translation of mRNAs
      of genes for non-canonical autophagy induction.

PMID- 28518138
TI  - Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and
      endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism.
AB  - Continued oxidative stress can lead to chronic inflammation, which in turn could
      mediate most chronic diseases including cancer. Nuclear factor erythroid 2
      related factor (Nrf2), a critical transcriptional activator for antioxidative
      responses, has envolved to be an attractive drug target for the treatment or
      prevention of human diseases. In the present study, we investigated the effects
      and mechanisms of betulin on Nrf2 activation and its involvement in the
      lipopolysaccharide (LPS)-triggered inflammatory system. In macrophages, betulin
      activated the Nrf2 signaling pathway and increased Nrf2-targeted antioxidant and
      detoxifying enzymes, including NADPH, quinine oxidoreductase 1 (NQO1), heme
      oxygenase-1 (HO-1), gamma-glutamyl cysteine synthetase catalytic subunit (GCLC)
      and modifier subunit (GCLM) in a dose and time dependent manner. Importantly, we
      found betulin-induced activation of Nrf2 is AMPK/AKT/GSK3beta dependent, as
      pharmacologically inactivating AMPK blocked the activating effect of betulin on
      AKT, GSK3beta and Nrf2. Furthermore, betulin attenuated LPS-induced inflammatory
      mediators (iNOS and COX-2) and MAPK inflammatory signaling pathway. The effect of
      betulin on HO-1 and NQO1 upregulation, iNOS and COX-2 the downregulation, and
      survival time extension was largely weakened when Nrf2 was depleted in vitro and
      in vivo. Our results demonstrate that the AMPK/AKT/Nrf2 pathways are essential
      for the anti-inflammatory effects of betulin in LPS-stimulated macrophages and
      endotoxin-shocked mice.

PMID- 28518137
TI  - Nerve growth factor from Chinese cobra venom stimulates chondrogenic
      differentiation of mesenchymal stem cells.
AB  - Growth factors such as transforming growth factor beta1 (TGF-beta1), have
      critical roles in the regulation of the chondrogenic differentiation of
      mesenchymal stem cells (MSCs), which promote cartilage repair. However, the
      clinical applications of the traditional growth factors are limited by their high
      cost, functional heterogeneity and unpredictable effects, such as cyst formation.
      It may be advantageous for cartilage regeneration to identify a low-cost
      substitute with greater chondral specificity and easy accessibility. As a
      neuropeptide, nerve growth factor (NGF) was involved in cartilage metabolism and
      NGF is hypothesized to mediate the chondrogenic differentiation of MSCs. We
      isolated NGF from Chinese cobra venom using a three-step procedure that we had
      improved upon from previous studies, and investigated the chondrogenic potential
      of NGF on bone marrow MSCs (BMSCs) both in vitro and in vivo. The results showed
      that NGF greatly upregulated the expression of cartilage-specific markers. When
      applied to cartilage repair for 4, 8 and 12 weeks, NGF-treated BMSCs have greater
      therapeutic effect than untreated BMSCs. Although inferior to TGF-beta1 regarding
      its chondrogenic potential, NGF showed considerably lower expression of collagen
      type I, which is a fibrocartilage marker, and RUNX2, which is critical for
      terminal chondrocyte differentiation than TGF-beta1, indicating its chondral
      specificity. Interestingly, NGF rarely induced BMSCs to differentiate into a
      neuronal phenotype, which may be due to the presence of other chondrogenic
      supplements. Furthermore, the underlying mechanism revealed that NGF-mediated
      chondrogenesis may be associated with the activation of PI3K/AKT and MAPK/ERK
      signaling pathways via the specific receptor of NGF, TrkA. In addition, NGF is
      easily accessed because of the abundance and low price of cobra venom, as well as
      the simplified methods for separation and purification. This study was the first
      to demonstrate the chondrogenic potential of NGF, which may provide a reference
      for cartilage regeneration in the clinic.

PMID- 28518140
TI  - A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial
      cell apoptosis.
AB  - Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting
      in endothelial cell dysfunction that is associated with cardiovascular disease.
      However, there is still limited information on the role of miRNA in serum
      deprivation-induced apoptosis. Here we found that serum deprivation increased
      caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering
      expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was
      highly correlated with suppressed expression levels of Dicer and Argonaute 2
      (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum
      deprived conditions. The decreased miR-101-3p caused elevated Bim expression by
      targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the
      intrinsic pathway of apoptosis via interaction with Bcl-2, decreased
      mitochondrial membrane potential, cytochrome c release, mitochondrial reactive
      oxygen species (ROS) production, and caspase activation. These events were
      abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a
      determinant role of the miR-101-3p/Bim axis in serum deprivation-induced
      apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is
      mediated by both caspase-3 and -1, which are activated by two distinct intrinsic
      mechanisms, cytochrome c release and ROS-induced inflammasome activation,
      respectively. In other words, the antioxidant inhibited endothelial cell death
      mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings
      provide mechanistic insight into a novel function of miR-101-3p in serum
      withdrawal-induced apoptosis triggered by activating two different intrinsic or
      mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target
      that limits endothelial cell death associated with vascular disorders.

PMID- 28518139
TI  - MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt
      pathway in breast cancer.
AB  - Accumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve
      in the tumorigenesis, progression and even lead to poor prognosis of various
      carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p
      (miR-93) levels were confirmed to be significantly upregulated in breast cancer
      clinical samples (n=36) and metastatic cell line (MDA-MB-231) compared with those
      in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A).
      Moreover, further research stated that the capability of migration, invasion and
      proliferation changed along with the altered expression of miR-106b and miR-93 in
      breast cancer. PTEN, the tumor-suppressor gene, was discovered to be reduced in
      breast cancer tissues or MDA-MB-231 cells with high levels of miR-106b and miR
      93, which were inversely expressed in PTEN overexpression tissues or cells. Based
      on the investigation, miR-106b and miR-93 induced the migration, invasion and
      proliferation and simultaneously enhanced the activity of phosphatidylinositol-3
      kinase (PI3K)/Akt pathway of MCF-7 cells, which could be blocked by upregulation
      of PTEN. Furthermore, suppression of PTEN reversed the function induced by anti
      miR-106b and anti-miR-93 in MDA-MB-231 cells, indicating that PTEN was directly
      targeted by these miRNAs and acted as the potential therapeutic target for breast
      cancer therapy. In short, reductive PTEN mediated by miR-106b and miR-93 promoted
      cell progression through PI3K/Akt pathway in breast cancer.

PMID- 28518141
TI  - CAF-secreted CXCL1 conferred radioresistance by regulating DNA damage response in
      a ROS-dependent manner in esophageal squamous cell carcinoma.
AB  - Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients
      treated with radiotherapy is <20%. Our study aimed to investigate whether cancer
      associated fibroblasts (CAFs), one major component of tumor microenvironment,
      were involved in tumor radioresistance in ESCC. By use of human
      chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed
      in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1
      expression in CAFs significantly reversed CAF-conferred radioresistance in vitro
      and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen
      species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS
      accumulation following radiation, by which DNA damage repair was enhanced and the
      radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance
      also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells
      induced CXCL1 expression in an autocrine/paracrine signaling loop, which further
      enhanced tumor radioresistance. Together, our study highlighted CAF-secreted
      CXCL1 as an attractive target to reverse tumor radioresistance and can be used as
      an independent prognostic factor of ESCC patients treated with chemoradiotherapy.

PMID- 28518142
TI  - MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells
      in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and
      TGFBR2.
AB  - Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs
      throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been
      shown to be involved in the biological processes, but the role and molecular
      mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a
      significant reduction in the expression of miR-130a-3p in livers of a mouse model
      with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients,
      and in activated hepatic stellate cells (HSCs). A dual-luciferase activity assay
      confirmed that transforming growth factor-beta receptors (TGFBRs) 1 and 2 were
      both the target genes of miR-130a-3p. The hepatic expression of TGFBR1 and TGFBR2
      was significantly increased. Moreover, the overexpression of miR-130a-3p in HSCs
      inhibited HSC activation and proliferation, concomitant with the decreased
      expression of TGFBR1, TGFBR2, Smad2, Smad3, matrix metalloproteinase-2 (MMP-2),
      MMP-9, type I collagen (Col-1), and Col-4. In addition, the overexpression of miR
      130a-3p promoted HSC apoptosis by inducing the expression of caspase-dependent
      apoptosis genes. Transfection with si-TGFBR1 and si-TGFBR2 revealed effects on
      HSC function that were consistent with those of miR-130a-3p. TGFBR1 and TGFBR2
      rescued the miR-130a-3p-mediated reductions in the mRNA and protein expression
      levels of Smad2, Smad3, Col-1, and Col-4. In conclusion, our findings suggest
      that miR-130a-3p might play a critical role in negatively regulating HSC
      activation and proliferation in the progression of nonalcoholic fibrosing
      steatohepatitis by directly targeting TGFBR1 and TGFBR2 via the TGF-beta/SMAD
      signaling pathway.

PMID- 28518143
TI  - Calcium sensing receptor protects high glucose-induced energy metabolism disorder
      via blocking gp78-ubiquitin proteasome pathway.
AB  - Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the
      patients with diabetes. The calcium sensing receptor (CaSR) is a G protein
      coupled receptor, which is involved in maintaining calcium homeostasis,
      regulating cell proliferation and apoptosis, and so on. In our previous study, we
      found that CaSR expression, intracellular calcium levels and cardiac function
      were all significantly decreased in DCM rats; however, the exact mechanism are
      not clear yet. The present study revealed the protective role of CaSR in
      myocardial energy metabolism disorder induced by high glucose (HG) as well as the
      underlying mechanism. Here, we demonstrated that HG decreased the expression of
      CaSR, mitochondrial fusion proteins (Mfn1, Mfn2), cell gap junction related
      proteins (Cx43, beta-catenin, N-cadherin), and intracellular ATP concentration.
      In contrast, HG increased extracellular ATP concentration, the expression of
      gp78, mitochondrial fission proteins (Fis1, Drp1), and the ubiquitination levels
      of Mfn1, Mfn2 and Cx43. Moreover, CaSR agonist and gp78-siRNA significantly
      reduced the above changes. Taken together, these results suggest that HG induces
      myocardial energy metabolism disorder via decrease of CaSR expression, and
      activation of gp78-ubiquitin proteasome system. In turn, these effects disrupt
      the structure and function of the mitochondria and the cell gap junction, result
      in the reduced ATP synthesis and the increased ATP leakage. Stimulation of CaSR
      significantly attenuates HG-induced abnormal myocardial energy metabolism,
      suggesting CaSR would be a promising potential therapeutic target for DCM.

PMID- 28518144
TI  - MicroRNA-23b functions as an oncogene and activates AKT/GSK3beta/beta-catenin
      signaling by targeting ST7L in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life
      worldwide, whereas the etiology and pathogenesis of HCC have not been fully
      determined. In the past few years, many microRNAs (miRNAs) have been proved to
      have important roles in tumorigenesis of HCC. In this study, we found that miR
      23b was significantly upregulated in tumor tissues of HCC patients. Functional
      tests showed that miR-23b could promote HCC cell proliferation and metastasis in
      vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a
      direct target of miR-23b and involved in the promotion effects of miR-23b on HCC
      tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could
      interact with the carboxyl terminal region of AKT and suppress AKT/GSK3beta/beta
      catenin pathway in HCC cells. In conclusion, our study revealed important roles
      of miR-23b and ST7L in progression of HCC.

PMID- 28518146
TI  - Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of
      PKCzeta-p53-p21 signaling pathway.
AB  - Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that
      catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However,
      canonical and non-canonical functions of ACOT7 remain to be discovered. In this
      study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses
      such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and
      dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the
      p53-p21 signaling pathway without a DNA damage response. PKCzeta was specifically
      involved in ACOT7 depletion-mediated cell cycle arrest as an upstream molecule of
      the p53-p21 signaling pathway in MCF7 human breast carcinoma and A549 human lung
      carcinoma cells. Of the other members of the ACOT family, including ACOT1, 4, 8,
      9, 11, 12, and 13 that were expressed in human, ACOT4, 8, and 12 were responsive
      to genotoxic stresses. However, none of those had a role in cytostasis via
      activation of the PKCzeta-p53-p21 signaling pathway. Analysis of the ACOT7
      prognostic value revealed that low ACOT7 levels prolonged overall survival
      periods in breast and lung cancer patients. Furthermore, ACOT7 mRNA levels were
      higher in lung cancer patient tissues compared to normal tissues. We also
      observed a synergistic effect of ACOT7 depletion in combination with either IR or
      doxorubicin on cell proliferation in breast and lung cancer cells. Together, our
      data suggest that a low level of ACOT7 may be involved, at least in part, in the
      prevention of human breast and lung cancer development via regulation of cell
      cycle progression.

PMID- 28518145
TI  - Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer.
AB  - Cytotoxic chemotherapy agents (e.g., cisplatin) are the first-line drugs to treat
      non-small cell lung cancer (NSCLC) but NSCLC develops resistance to the agent,
      limiting therapeutic efficacy. Despite many approaches to identifying the
      underlying mechanism for cisplatin resistance, there remains a lack of effective
      targets in the population that resist cisplatin treatment. In this study, we
      sought to investigate the role of cytoplasmic RAP1, a previously identified
      positive regulator of NF-kappaB signaling, in the development of cisplatin
      resistance in NSCLC cells. We found that the expression of cytoplasmic RAP1 was
      significantly higher in high-grade NSCLC tissues than in low-grade NSCLC;
      compared with a normal pulmonary epithelial cell line, the A549 NSCLC cells
      exhibited more cytoplasmic RAP1 expression as well as increased NF-kappaB
      activity; cisplatin treatment resulted in a further increase of cytoplasmic RAP1
      in A549 cells; overexpression of RAP1 desensitized the A549 cells to cisplatin,
      and conversely, RAP1 depletion in the NSCLC cells reduced their proliferation and
      increased their sensitivity to cisplatin, indicating that RAP1 is required for
      cell growth and has a key mediating role in the development of cisplatin
      resistance in NSCLC cells. The RAP1-mediated cisplatin resistance was associated
      with the activation of NF-kappaB signaling and the upregulation of the
      antiapoptosis factor BCL-2. Intriguingly, in the small portion of RAP1-depleted
      cells that survived cisplatin treatment, no induction of NF-kappaB activity and
      BCL-2 expression was observed. Furthermore, in established cisplatin-resistant
      A549 cells, RAP1 depletion caused BCL2 depletion, caspase activation and dramatic
      lethality to the cells. Hence, our results demonstrate that the cytoplasmic RAP1
      NF-kappaB-BCL2 axis represents a key pathway to cisplatin resistance in NSCLC
      cells, identifying RAP1 as a marker and a potential therapeutic target for
      cisplatin resistance of NSCLC.

PMID- 28518147
TI  - Survivin, a key player in cancer progression, increases in obesity and protects
      adipose tissue stem cells from apoptosis.
AB  - Adipose tissue (AT) has a central role in obesity-related metabolic imbalance
      through the dysregulated production of cytokines and adipokines. In addition to
      its known risk for cardiovascular disease and diabetes, obesity is also a major
      risk for cancer. We investigated the impact of obesity for the expression of
      survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic
      biomarker of tumor onset and recurrence. In a cross-sectional study of 111
      subjects classified by body mass index, circulating levels of survivin and gene
      expression in subcutaneous AT were significantly higher in obese patients and
      positively correlated with leptin. Within AT, survivin was primarily detected in
      human adipocyte-derived stem cells (hASCs), the adipocyte precursors that
      determine AT expansion. Remarkably, survivin expression was significantly higher
      in hASCs isolated from obese patients that from lean controls and was increased
      by proinflammatory M1 macrophage soluble factors including IL-1beta. Analysis of
      survivin expression in hASCs revealed a complex regulation including epigenetic
      modifications and protein stability. Surprisingly, obese hASCs showed survivin
      promoter hypermethylation that correlated with a significant decrease in its mRNA
      levels. Nonetheless, a lower level of mir-203, which inhibits survivin protein
      translation, and higher protein stability, was found in obese hASCs compared with
      their lean counterparts. We discovered that survivin levels determine the
      susceptibility of hASCs to apoptotic stimuli (including leptin and hypoxia).
      Accordingly, hASCs from an obese setting were protected from apoptosis.
      Collectively, these data shed new light on the molecular mechanisms governing AT
      expansion in obesity through promotion of hASCs that are resistant to apoptosis,
      and point to survivin as a potential new molecular player in the communication
      between AT and tumor cells. Thus, inhibition of apoptosis targeting survivin
      might represent an effective strategy for both obesity and cancer therapy.

PMID- 28518148
TI  - Hepatocyte polyploidization and its association with pathophysiological
      processes.
AB  - A characteristic cellular feature of the mammalian liver is the progressive
      polyploidization of the hepatocytes, where individual cells acquire more than two
      sets of chromosomes. Polyploidization results from cytokinesis failure that takes
      place progressively during the course of postnatal development. The proportion of
      polyploidy also increases with the aging process or with cellular stress such as
      surgical resection, toxic stimulation, metabolic overload, or oxidative damage,
      to involve as much as 90% of the hepatocytes in mice and 40% in humans.
      Hepatocyte polyploidization is generally considered an indicator of terminal
      differentiation and cellular senescence, and related to the dysfunction of
      insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of
      hepatocyte polyploidization in the aged mouse liver can be reversed when the
      senescent hepatocytes are serially transplanted into young mouse livers. Here we
      review the current knowledge on the mechanism of hepatocytes polyploidization
      during postnatal growth, aging, and liver diseases. The biologic significance of
      polyploidization in senescent reversal, within the context of new ways to think
      of liver aging and liver diseases is considered.

PMID- 28518149
TI  - Rnf138 deficiency promotes apoptosis of spermatogonia in juvenile male mice.
AB  - Spermatogenesis, the process by which haploid sperm cells are produced from a
      diploid precursor cell, is essential for sexual reproduction. Here, we report
      that RING-finger protein 138 (Rnf138) is highly expressed in testes, especially
      in spermatogonia and spermatocytes. The role of Rnf138 in spermatogenesis was
      examined using a Rnf138-knockout mouse model. Rnf138 deficiency resulted in
      increased apoptosis in spermatogenic cells, loss of proliferative spermatogonia,
      delayed development of spermatozoa and impaired fertility. The proportion of
      PLZF+Ki67+ cells within the PLZF+ population decreased in the knockout mice. The
      phenotype was further assessed by RNA-sequencing (RNA-seq), which determined that
      the expression levels of many genes involved in spermatogenesis were altered in
      the testis of Rnf138-knockout mice. Thus, Rnf138 deficiency promotes the
      apoptosis of spermatogenic cells, which may have been caused by the aberrant
      proliferation of spermatogonia in mouse testis development.

PMID- 28518150
TI  - Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in
      glioblastoma multiforme.
AB  - Cancer is the second leading cause of death worldwide. Current treatment
      strategies based on multi-agent chemotherapy and/or radiation regimens have
      improved overall survival in some cases. However, resistance to apoptosis often
      develops in cancer cells, and its occurrence is thought to contribute to
      treatment failure. Non-apoptotic cell death mechanisms have become of great
      interest, therefore, in hopes that they would bypass tumor cell resistance.
      Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent
      brain tumor in adults, and has a high rate of mortality. We report that NIM811, a
      small molecule cyclophilin-binding inhibitor, induces catastrophic vacuolization
      and cell death in GBM cells. These unique features are distinct from many known
      cell death pathways, and are associated with an incompletely defined cell death
      mechanism known as paraptosis. We found that NIM811-induced paraptosis is due to
      unresolved ER stress. The abnormal upregulation of protein translation was
      responsible for the build-up of misfolded or unfolded proteins in ER, whereas pro
      survival autophagy and UPR signals were shutdown during prolonged treatment with
      NIM811. Although cycloheximide has been claimed to suppress paraptosis, instead
      we find that it only temporarily delayed vacuole formation, but actually enhanced
      paraptotic cell death in the long term. On the other hand, mTOR inhibitors
      rescued cells from NIM811-induced paraptosis by sustaining autophagy and the UPR,
      while specifically restraining cap-dependent translation. These findings not only
      provide new insights into the mechanisms underlying paraptosis, but also shed
      light on a potential approach to enhance GBM treatment.

PMID- 28518153
TI  - Enchained growth.

PMID- 28518152
TI  - STAT5 alters the state of transcriptional networks, driving aggressive leukemia.

PMID- 28518151
TI  - Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in
      vivo by simultaneous induction of ROS-JNK and inhibition of NF-kappaB and Nrf2.
AB  - Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances
      in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem
      cells (LSCs) is the major cause of the recurrence of AML even after aggressive
      treatment making, promoting development of LSC-targeted agents is an urgent
      clinical need. Although the antitumor activity of disulfiram (DS), an approved
      anti-alcoholism drug, has been demonstrated in multiple types of tumors including
      hematological malignancies such as AML, it remains unknown whether this agent
      would also be able to target cancer stem cells like LSCs. Here, we report the in
      vitro and in vivo activity of DS in combination with copper (Cu) against
      CD34+/CD38+ leukemia stem-like cells sorted from KG1alpha and Kasumi-1 AML cell
      lines, as well as primary CD34+ AML samples. DS plus Cu (DS/Cu) displayed marked
      inhibition of proliferation, induction of apoptosis, and suppression of colony
      formation in cultured AML cells while sparing the normal counterparts. DS/Cu also
      significantly inhibited the growth of human CD34+/CD38+ leukemic cell-derived
      xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was
      closely associated with activation of the stress-related ROS-JNK pathway as well
      as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-kappaB
      pathways. In summary, our findings indicate that DS/Cu selectively targets
      leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising
      LSC-targeted activity of this repurposed agent for treatment of relapsed and
      refractory AML.

PMID- 28518155
TI  - Monocyte and DC atlas.

PMID- 28518157
TI  - Erratum: THEMIS enhances TCR signaling and enables positive selection by
      selective inhibition of the phosphatase SHP-1.

PMID- 28518158
TI  - Unusual suspects: dancing with stromal cells.

PMID- 28518154
TI  - IL-17+ gammadelta T cells as kick-starters of inflammation.
AB  - Shortly after the discovery of interleukin 17 (IL-17)-producing CD4+ helper T
      cells (TH17 cells), it was found that gammadelta T cells can also secrete large
      amounts of this pro-inflammatory cytokine. A decade later, it is now known that
      IL-17+ gammadelta T cells (gammadelta17 T cells) are often the main providers of
      IL-17A in various models of inflammatory diseases, while they also contribute to
      protective immune responses to infectious organisms. Due to an intricate thymic
      program of differentiation, gammadelta17 T cells are able to respond faster than
      TH17 cells do and thus predominate in the early stages of inflammatory responses.
      Here we review the current knowledge of the development, activation and
      pathophysiological functions of gammadelta17 T cells, aiming to increase the
      awareness in the community of the therapeutic potential of this 'other side' of
      IL-17-mediated immune responses.

PMID- 28518160
TI  - Superinduction!

PMID- 28518161
TI  - Erratum: Epigenetic landscapes reveal transcription factors that regulate CD8+ T
      cell differentiation.

PMID- 28518159
TI  - Alternative monocytes settle in for the long term.

PMID- 28518156
TI  - Interleukin 17 is a chief orchestrator of immunity.
AB  - Increased understanding of the biology of interleukin 17 (IL-17) has revealed
      that this cytokine is a central player in immunity at the sites most exposed to
      microorganisms. Although it has been strongly associated with immunopathology, IL
      17 also has an important role in host defense. The regulation of IL-17 secretion
      seems to be shared among various cell types, each of which can concomitantly
      secrete additional products. IL-17 has only modest activity on its own; its
      impact in immunity arises from its synergistic action with other factors, its
      self-sustaining feedback loop and, in some cases, its role as a counterpart of
      interferon-gamma (IFN-gamma). Together these attributes provide a robust response
      against microorganisms, but they can equally contribute to immune pathology. Here
      we focus on a discussion of the role of IL-17 during infection.

PMID- 28518162
TI  - Zika-neutralizing antibodies.

PMID- 28518163
TI  - Exploitation by Mtb.

PMID- 28518164
TI  - Fertilization and nucleic acid sensing.

PMID- 28518165
TI  - Erratum: CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells
      clears Chlamydia muridarum from the arterial intima.

PMID- 28518166
TI  - Corrigendum: Quantifying the shifting landscape of B cell immunodominance.

PMID- 28518167
TI  - RNA-binding proteins, the guardians of the marginal zone.

PMID- 28518169
TI  - Population-based impact of noninvasive prenatal screening on screening and
      diagnostic testing for fetal aneuploidy.
AB  - PurposeTo assess the population-wide impact of noninvasive prenatal screening
      (NIPS) on combined first-trimester screening (CFTS), early ultrasound (11-13
      weeks), and invasive prenatal diagnosis in a state with over 73,000 births per
      year.MethodsAnalysis of population-based data from 2000 to 2015 including (i)
      invasive prenatal tests, (ii) CFTS uptake, and (iii) total births. Utilization of
      early ultrasound was analyzed before and after NIPS (2010-2015).ResultsInvasive
      testing decreased significantly by 39.6% from 2012 to 2015 despite steady births.
      More than half of all confirmed cases of trisomy 21 were ascertained by NIPS in
      2015, despite NIPS comprising only 11.7% of total indications for invasive
      testing. CFTS uptake declined significantly from 77.5% in 2013 to 68.1% in 2015,
      but 11- to 13-week ultrasounds did not. In 2015, ultrasound abnormality replaced
      CFTS as the most common indication for invasive testing and chromosomal
      microarray was performed for 85.3% of all prenatal karyotypes.ConclusionPrenatal
      testing is now unequivocally in the genomic era. NIPS is now the screening test
      that precedes the majority of confirmed diagnoses of trisomy 21. The
      contributions of NIPS, early ultrasound, and chromosome microarray have led to
      unprecedented detection rates of major chromosome abnormalities, now found in 20%
      of all invasive tests.

PMID- 28518168
TI  - Using high-resolution variant frequencies to empower clinical genome
      interpretation.
AB  - PurposeWhole-exome and whole-genome sequencing have transformed the discovery of
      genetic variants that cause human Mendelian disease, but discriminating
      pathogenic from benign variants remains a daunting challenge. Rarity is
      recognized as a necessary, although not sufficient, criterion for pathogenicity,
      but frequency cutoffs used in Mendelian analysis are often arbitrary and overly
      lenient. Recent very large reference datasets, such as the Exome Aggregation
      Consortium (ExAC), provide an unprecedented opportunity to obtain robust
      frequency estimates even for very rare variants.MethodsWe present a statistical
      framework for the frequency-based filtering of candidate disease-causing
      variants, accounting for disease prevalence, genetic and allelic heterogeneity,
      inheritance mode, penetrance, and sampling variance in reference
      datasets.ResultsUsing the example of cardiomyopathy, we show that our approach
      reduces by two-thirds the number of candidate variants under consideration in the
      average exome, without removing true pathogenic variants (false-positive
      rate<0.001).ConclusionWe outline a statistically robust framework for assessing
      whether a variant is "too common" to be causative for a Mendelian disorder of
      interest. We present precomputed allele frequency cutoffs for all variants in the
      ExAC dataset.

PMID- 28518170
TI  - Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges.
AB  - PurposeWe investigated the diagnostic and clinical performance of exome
      sequencing in fetuses with sonographic abnormalities with normal karyotype and
      microarray and, in some cases, normal gene-specific sequencing.MethodsExome
      sequencing was performed on DNA from 15 anomalous fetuses and from the peripheral
      blood of their parents. Parents provided consent to be informed of diagnostic
      results in the fetus, medically actionable findings in the parents, and their
      identification as carrier couples for significant autosomal recessive conditions.
      We assessed the perceptions and understanding of exome sequencing using mixed
      methods in 15 mother-father dyads.ResultsIn seven (47%) of 15 fetuses, exome
      sequencing provided a diagnosis or possible diagnosis with identification of
      variants in the following genes: COL1A1, MUSK, KCTD1, RTTN, TMEM67, PIEZO1 and
      DYNC2H1. One additional case revealed a de novo nonsense mutation in a novel
      candidate gene (MAP4K4). The perceived likelihood that exome sequencing would
      explain the results (5.2 on a 10-point scale) was higher than the approximately
      30% diagnostic yield discussed in pretest counseling.ConclusionExome sequencing
      had diagnostic utility in a highly select population of fetuses where a genetic
      diagnosis was highly suspected. Challenges related to genetics literacy and
      variant interpretation must be addressed by highly tailored pre- and posttest
      genetic counseling.

PMID- 28518171
TI  - FISH-Flow, a protocol for the concurrent detection of mRNA and protein in single
      cells using fluorescence in situ hybridization and flow cytometry.
AB  - We describe a flow-cytometry-based protocol for intracellular mRNA measurements
      in nonadherent mammalian cells using fluorescence in situ hybridization (FISH)
      probes. The method, which we call FISH-Flow, allows for high-throughput
      multiparametric measurements of gene expression, a task that was not feasible
      with earlier, microscopy-based approaches. The FISH-Flow protocol involves cell
      fixation, permeabilization and hybridization with a set of fluorescently labeled
      oligonucleotide probes. In this protocol, surface and intracellular protein
      markers can also be stained with fluorescently labeled antibodies for
      simultaneous protein and mRNA measurement. Moreover, a semiautomated, single-tube
      version of the protocol can be performed with a commercially available cell-wash
      device that reduces cell loss, operator time and interoperator variability. It
      takes ~30 h to perform this protocol. An example of FISH-Flow measurements of
      cytokine mRNA induction by ex vivo stimulation of primed T cells with specific
      antigens is described.

PMID- 28518174
TI  - Cardiac resuscitation: Benefit of bystander CPR and defibrillation.

PMID- 28518173
TI  - Simultaneous quantification of N- and O-glycans using a solid-phase method.
AB  - Glycosylation has a pivotal role in a diverse range of biological activities,
      modulating the structure and function of proteins. Glycogens coupled to the
      nitrogen atom (N-linked) of asparagine side chains or to the oxygen atom (O
      linked) of serine and threonine side chains represent the two major protein
      glycosylation forms. N-glycans can be released by glycosidases, whereas O-glycans
      are often cleaved by chemical reaction. However, it is challenging to combine
      these enzymatic and chemical reactions in order to analyze both N- and O-glycans.
      We recently developed a glycoprotei n immobilization for glycan extraction (GIG)
      method that allows for the simultaneous analysis of N- and O-glycans on a solid
      support. GIG enables quantitative analysis of N-glycans and O-glycans from a
      single specimen and can be applied to a high-throughput automated platform. Here
      we provide a step-by-step GIG protocol that includes procedures for (i) protein
      immobilization on an aldehyde-active solid support by reductive amination; (ii)
      stabilization of fragile sialic acids by carbodiimide coupling; (iii) release of
      N-glycans by PNGase F digestion; (iv) release of O-glycans by beta-elimination
      using ammonia in the presence of 1-phenyl-3-methyl-5-pyrazolone (PMP) to prevent
      alditol peeling from O-glycans; (v) mass spectrometry (MS) analysis; and (vi)
      data analysis for identification of glycans using in-house developed software
      (GIG Tool; free to download via http://www.biomarkercenter.org/gigtool). The GIG
      tool extracts precursor masses, oxonium ions and glycan fragments from tandem
      (liquid chromatography (LC)-MS/MS) mass spectra for glycan identification, and
      reporter ions from quaternary amine containing isobaric tag for glycan (QUANTITY)
      isobaric tags are used for quantification of the relative abundance of N-glycans.
      The GIG protocol takes ~3 d.

PMID- 28518175
TI  - Dyslipidaemia: HDL-related biomarkers of cardiovascular risk.

PMID- 28518177
TI  - Genetics: Smoking reduces genetic protection against CHD.

PMID- 28518172
TI  - Super-resolution microscopy with DNA-PAINT.
AB  - Super-resolution techniques have begun to transform biological and biomedical
      research by allowing researchers to observe structures well below the classic
      diffraction limit of light. DNA points accumulation for imaging in nanoscale
      topography (DNA-PAINT) offers an easy-to-implement approach to localization-based
      super-resolution microscopy, owing to the use of DNA probes. In DNA-PAINT,
      transient binding of short dye-labeled ('imager') oligonucleotides to their
      complementary target ('docking') strands creates the necessary 'blinking' to
      enable stochastic super-resolution microscopy. Using the programmability and
      specificity of DNA molecules as imaging and labeling probes allows researchers to
      decouple blinking from dye photophysics, alleviating limitations of current super
      resolution techniques, making them compatible with virtually any single-molecule
      compatible dye. Recent developments in DNA-PAINT have enabled spectrally
      unlimited multiplexing, precise molecule counting and ultra-high, molecular-scale
      (sub-5-nm) spatial resolution, reaching ~1-nm localization precision. DNA-PAINT
      can be applied to a multitude of in vitro and cellular applications by linking
      docking strands to antibodies. Here, we present a protocol for the key aspects of
      the DNA-PAINT framework for both novice and expert users. This protocol describes
      the creation of DNA origami test samples, in situ sample preparation, multiplexed
      data acquisition, data simulation, super-resolution image reconstruction and post
      processing such as drift correction, molecule counting (qPAINT) and particle
      averaging. Moreover, we provide an integrated software package, named Picasso,
      for the computational steps involved. The protocol is designed to be modular, so
      that individual components can be chosen and implemented per requirements of a
      specific application. The procedure can be completed in 1-2 d.

PMID- 28518178
TI  - Physical function and exercise training in older patients with heart failure.
AB  - Heart failure (HF) is a common end point for numerous cardiovascular conditions,
      including coronary artery disease, valvular disease, and hypertension. HF
      predominantly affects older individuals (aged >=70 years), particularly those
      living in developed countries. The pathophysiological sequelae of HF progression
      have a substantial negative effect on physical function. Diminished physical
      function in older patients with HF, which is the result of combined disease
      related and age-related effects, has important implications on health. A large
      body of research spanning several decades has demonstrated the safety and
      efficacy of regular physical activity in improving outcomes among the HF
      population, regardless of age, sex, or ethnicity. However, patients with HF,
      especially those who are older, are less likely to engage in regular exercise
      training compared with the general population. To improve initiation of regular
      exercise training and subsequent long-term compliance, there is a need to rethink
      the dialogue between clinicians and patients. This Review discusses the need to
      improve physical function and exercise habits in patients with HF, focusing on
      the older population.

PMID- 28518179
TI  - Cleaning, Disinfection, and Sterilization Protocols Employed for Customized
      Implant Abutments: An International Survey of 100 Universities Worldwide.
AB  - PURPOSE: American and European standards recommend sterilization of customized
      abutments before connecting them to implants, as customized abutments are
      considered semi-critical medical devices. Since standardized procedures could not
      be identified in the literature on implantology, this survey evaluated the
      protocols employed at different universities worldwide to clean, disinfect,
      and/or sterilize customized abutments before their connection to bone-level
      implants. MATERIALS AND METHODS: The survey took place between October 2015 and
      January 2016. A single question acquiring information on how customized abutments
      were treated prior to connection to the implants was sent by email to researchers
      affiliated at 100 universities worldwide. To avoid any bias, the survey was kept
      rigorously anonymous. A total of 100 universities from Europe (56), USA and
      Canada (25), Latin America (9), South Africa (1), Asia (6), and Australia and New
      Zealand (3) were invited to participate in the survey. RESULTS: Altogether, 85
      universities responded to the survey question, and 22 (25.9%) declared that no
      cleaning protocols were adopted. More than half of the respondents (n = 49,
      57.6%) performed only one of the three procedures required by the standards
      (cleaning, disinfection, or sterilization). Twelve respondents (14.1%) adopted
      two procedures, and only two universities performed all three required procedures
      (2.4%). CONCLUSION: This survey indicated substantial heterogeneity in treating
      customized abutments before connecting them to implants. This study demonstrated
      that the majority of the universities applied either cleaning, disinfection, or
      sterilization which may not meet the prevailing standards.

PMID- 28518180
TI  - The Effects of Laser with Different Parameters and Crosshatching on Fibroblast
      Adhesion and Proliferation to Implant Surfaces.
AB  - PURPOSE: To compare the adhesion and proliferation effect of HGF-1 cells on pure
      titanium disks when the surfaces are unprocessed (machined surfaces after
      slicing) or modified with a laser. MATERIALS AND METHODS: Twenty-eight titanium
      disks were divided into four groups. Three surface topographies were created
      using an erbium fiber laser: group 1 (unidirectional application [no
      crosshatch]), group 2 (crosshatching in two directions), and group 3
      (crosshatching in three directions). The samples in group 4 were unprocessed and
      served as controls. The surface roughness of samples was investigated with
      scanning electron microscopy (SEM) and measured with a mechanical surface
      profilometer. HGF-1 cell line was used to analyze the adhesion of fibroblasts on
      the sample surfaces. The authors used SEM, XTT, and acridine orange tests to
      determine the adhesion of HGF-1 onto specimen surfaces and the cell morphology
      after incubation for 72 hours. XTT results and surface roughness values for all
      specimens were analyzed using the Kruskal-Wallis test. RESULTS: Ra values of
      group 1 to group 4 (control) were 1.13, 0.26, 0.38, and 0.19, respectively.
      Crosshatching decreased the surface roughness values compared with unidirectional
      application (P = .003). Cell morphology observed in SEM showed that the
      elongation direction of cells resulted in all directions related with additional
      filopodia extentions within the crosshatch groups. Therefore, the highest cell
      viability was also detected in the three-directional crosshatch group (group 3)
      (P = .000) in XTT assay. According to the acridine orange test, higher cell
      numbers were seen in group 3, similar to the XTT findings (P = .86). CONCLUSION:
      Crosshatching significantly increased the cell-covered implant surfaces compared
      with the unidirectional group. Decreasing the surface Ra values via crosshatching
      helped spread the fibroblast over the implants in any direction, thus increasing
      cell proliferation and adhesion.

PMID- 28518176
TI  - Seasonal variations in cardiovascular disease.
AB  - Cardiovascular disease (CVD) follows a seasonal pattern in many populations.
      Broadly defined winter peaks and clusters of all subtypes of CVD after 'cold
      snaps' are consistently described, with corollary peaks linked to heat waves.
      Individuals living in milder climates might be more vulnerable to seasonality.
      Although seasonal variation in CVD is largely driven by predictable changes in
      weather conditions, a complex interaction between ambient environmental
      conditions and the individual is evident. Behavioural and physiological responses
      to seasonal change modulate susceptibility to cardiovascular seasonality. The
      heterogeneity in environmental conditions and population dynamics across the
      globe means that a definitive study of this complex phenomenon is unlikely.
      However, given the size of the problem and a range of possible targets to reduce
      seasonal provocation of CVD in vulnerable individuals, scope exists for both
      greater recognition of the problem and application of multifaceted interventions
      to attenuate its effects. In this Review, we identify the physiological and
      environmental factors that contribute to seasonality in nearly all forms of CVD,
      highlight findings from large-scale population studies of this phenomenon across
      the globe, and describe the potential strategies that might attenuate peaks in
      cardiovascular events during cold and hot periods of the year.

PMID- 28518183
TI  - Preclinical Evaluation of a Crown-Splinted Custom Root-Shaped Implant.
AB  - OBJECTIVE: To test whether a Maryland bridge-type splint provides adequate
      stability for a custom root-shaped implant to osseointegrate in a manner
      substantially equivalent to that of a threaded implant. METHODS: Six beagle dogs
      were subjected to intraoral impressions and cone beam scans that were used to
      fabricate custom root-shaped implants (RTIs) and crowns. Premolars in the
      mandible (P4) and in the maxilla (P3) were extracted, and 24 RTIs were
      immediately placed in extraction sockets. Splint extensions of the crowns were
      bonded to mesial and distal teeth. Twelve mandibular molars (M2) were extracted,
      and threaded implants (DXI), serving as controls, were placed immediately.
      Animals were placed on a soft diet after surgery. Weekly intraoral photographs
      and radiographs were taken, and animals were sacrificed at 4 months. Fluorescent
      labels were injected 35, 21, and 7 days before sacrifice. Clinical implant
      stability and vertical pullout forces were tested, and loss of vertical bone
      height was measured on radiographs. Histomorphometric measurements of percent
      bone-to-implant contact (BIC) and mineral apposition rates were made from
      undecalcified sections. RESULTS: Three RTI splints broke or debonded, and the
      implants were removed. No loss of DXI implants was noted. All remaining implants
      were clinically stable. Mean pullout forces were 366.7 +/- 182.8 N for RTI (no
      pullout data for the threaded DXI). Mean vertical bone loss was 0.4 +/- 0.6 mm
      mesially and 0.2 +/- 0.7 mm distally for RTI and 0.8 +/- 1.1 mm mesially and 0.8
      +/- 1.0 mm distally for DXI, with no significant differences between groups. BIC
      values were 70.8% +/- 12.7% for mandibular RTI, 68.3% +/- 11.6% for maxillary
      RTI, and 78.8% +/- 5.5% for DXI. Mineral apposition rates within local osteons
      were 1.9 +/- 0.5 MUm for RTI and 1.7 +/- 0.3 MUm for DXI; at the implant surface,
      they were 2.5 +/- 1.2 MUm for RTI and 3.3 +/- 1.8 MUm for DXI, with no
      significant differences between groups. CONCLUSION: All RTIs with intact splints
      exhibited clinically successful integration, similar to that of control threaded
      implants. The RTI may be a viable option for single-tooth replacement.

PMID- 28518181
TI  - A Semi-automatic Algorithm for Preliminary Assessment of Labial Gingiva and
      Alveolar Bone Thickness of Maxillary Anterior Teeth.
AB  - PURPOSE: Soft and hard tissue volumes are critical for implant placement and long
      term stability. Although the literature has adequately addressed tissue biotypes
      of Western populations, pertinent information about Asian populations is limited.
      This study aimed to evaluate the soft and hard tissue profiles of the maxillary
      anterior teeth of the Taiwanese population using a semi-automatic algorithm.
      MATERIALS AND METHODS: Cone beam computed tomography images of 11 adults with
      well-aligned maxillary anterior teeth were overlaid with those of cast models,
      based on the tooth crowns manually outlined by two independent observers. Each
      tooth was digitally trisected mesiodistally and apicocoronally. The thicknesses
      of the labial gingiva and alveolar bone were measured using a customized software
      program. RESULTS: No obvious difference between the observers was noted regarding
      the dimension of tooth crowns. The average thicknesses of the labial gingiva, the
      labial alveolar bone, and the palatal alveolar bone were 1.76 +/- 0.11 mm, 1.02
      +/- 0.12 mm, and 1.80 +/- 0.31 mm, respectively, with no significant differences
      between teeth. All parameters were thicker in the apical region than in the
      cervical region, and the alveolar bone was thinner in the midlabial region of
      incisors than in the interproximal regions. The thinnest areas were the
      midcervical compartment of the right central incisor (0.53 +/- 0.33 mm) for the
      labial gingiva, the midcervical compartment of the right lateral incisor (0.23 +/
      0.10 mm) for the labial alveolar bone, and the mesiocervical compartment of the
      left central incisor (0.33 +/- 0.09 mm) for the palatal alveolar bone.
      CONCLUSION: This study presents an objective and comprehensive methodology for
      evaluating the soft and hard tissue profiles of maxillary anterior teeth and may
      be of value for presurgical planning for immediate implant placement. The results
      suggest that profiles of the Taiwanese subjects are similar to profiles of
      Western populations.

PMID- 28518182
TI  - Triple-Layered Closure of an Oroantral Fistula: A Case Report.
AB  - Oroantral fistulae (OAF) are surgical sequelae that require complete resection
      and often leave large defects for the surgeon to repair. Closing these lesions is
      often technique sensitive and requires a detailed protocol, which, if not adhered
      to, can lead to recurrence. This case report presents a combined approach to
      closing an OAF by first excising the fistula and then resecting to retrieve the
      buccal fat pad to form a pedicle graft over the wound site. Next, a platelet-rich
      fibrin membrane is sandwiched over the buccal fat pad and completely covered by a
      buccal advancement flap. This triple-layered technique is a novel method to close
      a chronic OAF.

PMID- 28518184
TI  - A Method for Minimizing Rotational Errors of Implant Prostheses.
AB  - PURPOSE: Rotational errors of implants can occur during two stages: when
      connecting impression copings with implants, and when connecting impression
      copings with analogs. The aim of this study was to determine ways to minimize
      these rotational errors. MATERIALS AND METHODS: Three types of implants were
      prepared: a tissue-level implant with an internal octagon 8-degree Morse taper
      connection, a bone-level implant with an internal hex 11-degree Morse taper
      connection, and a bone-level implant with an external hex connection. Each
      complex (n = 10 per group) was composed of an implant, an impression coping, and
      an analog. Implants were embedded in resin blocks and connected with
      corresponding impression copings. Analogs that reproduced the position of the
      implants were created by means of a custom-made transfer jig, and rotational
      errors were measured between implants and analogs. Impression copings and analogs
      were connected by means of four methods: The impression coping was connected to
      the implant in a clockwise (CW) or a counterclockwise (CCW) direction before
      tightening, and the analogs were then connected with impression copings and
      tightened using a hemostat (Hs) or by hand (Hd). RESULTS: The CW-Hs and CCW-Hd
      groups exhibited low rotational error (mean +/- standard deviation 0.11 +/- 0.21
      and 0.19 +/- 0.34 degrees, respectively), whereas the CW-Hd and CCW-Hs groups
      exhibited high rotational error (-1.80 +/- 0.67 and 2.07 +/- 0.75, respectively)
      in different directions. A strong association was observed between the tightening
      method and rotational error, and a weak association was observed between the
      connection type and rotational error. CONCLUSION: The CW-Hs method was found to
      be the most suitable for minimizing rotational error between implants and
      analogs.

PMID- 28518185
TI  - Osteogenic Potential of Adipose-Derived Macrospheroids Cocultured with CD11b+
      Monocytes.
AB  - PURPOSE: Among potential cell-based therapies, adipose-derived stem cells (ASCs)
      have been proposed as a promising source of stem cells for tissue regeneration.
      Although many recent clinical trials have investigated the use of adipose tissue
      or ASCs in transplantation, analysis of the microstructures of outgrowing
      macrosized spheroids (macrospheroids) or three-dimensional coculture of ASC
      spheroids and monocyte/macrophage lineages has not been performed. The aim of
      this study was to analyze the microstructures of murine-derived ASC
      macrospheroids and the growth and osteogenic potential of these macrospheroids in
      a three-dimensional environment and after calcification induction by coculture
      with monocytes. MATERIALS AND METHODS: The histologic structures of murine
      derived ASC macrospheroids and the expression of marker genes for multipotency
      within these macrospheroids were analyzed by hematoxylin and eosin staining and
      in situ hybridization. ASC macrospheroid microstructures were observed by
      transmission electron microscopy, and cell proliferation in the spheroids was
      analyzed. Additionally, the growth and osteogenic potential of these
      macrospheroids were assessed in two-dimensional and three-dimensional
      environments and after calcification induction by coculture with monocytes.
      RESULTS: The expression of Oct3/4, Nanog, and Sox2 was detected even in the deep
      zone of spheroids, although higher expression was observed at the surface. Cell
      proliferation was detected within the spheroid centers. Observation of spheroid
      microstructure revealed extracellular matrix production within the spheroid
      architecture. Transplantation of a spheroid on the hydroxyapatite disc resulted
      in three-dimensional cell growth, filling the disc. Coculture of the spheroids
      with monocytes led to the formation of many osteoclast-like, multinucleated
      cells, and calcification was observed after 3 weeks of coculture. CONCLUSION: ASC
      spheroids exhibited high capacity for dynamic three-dimensional growth and
      osteogenic differentiation. Furthermore, ASC spheroids promoted monocyte
      differentiation into osteoclast-like cells, which may enhance the osteogenic
      potential of ASC spheroids.

PMID- 28518186
TI  - Molecular Activity and Osseointegration After Single-Dose Irradiation: An In Vivo
      Study.
AB  - PURPOSE: Irradiation results in deleterious effects on bone healing and
      integration of titanium implants. The impact of irradiation on osseointegration
      has been demonstrated in histologic studies, but the underlying molecular
      mechanisms have not been explored. This study aimed to investigate the effects of
      single-dose irradiation on the expression of biologic mediators crucial for
      inflammation, bone formation, and bone remodeling and to relate these molecular
      activities to implant stability after a 5-week healing period. MATERIALS AND
      METHODS: A rat tibia model was used. An external single-dose irradiation of 20 Gy
      was administered to one leg while the second leg was used as a control. After 8
      weeks, the irradiated and non-irradiated tibiae received titanium implants. Five
      weeks following implantation, implant stability was evaluated by removal torque
      measurement. Then, the implant and the bone surrounding the implant were
      retrieved for gene expression analysis of the implant-adherent cells and peri
      implant bone, respectively. RESULTS: Irradiation resulted in 55% reduction in
      removal torque. The implant-adherent cells in irradiated sites revealed
      downregulation of genes related to bone formation (ALP and OC) and upregulation
      of proinflammatory (TNF-alpha) and pro-fibrogenic (PDGF-b) genes. Conversely, the
      peri-implant bone in irradiated sites revealed upregulation of bone formation and
      bone remodeling genes. Removal torque showed a negative correlation with pro
      inflammatory activity and a positive correlation with osteoblastic activity in
      the implant-adherent cells. CONCLUSION: The impact of high (20 Gy) single-dose
      irradiation on osseointegration involves a reduction in bone formation activity
      and upregulation of pro-inflammatory and pro-fibrogenic activities in the implant
      adherent cells. It is also suggested that this single-dose irradiation elicits a
      different molecular pattern at a distance from the implant surface, characterized
      by increased bone formation and remodeling activities in the peri-implant bone.

PMID- 28518187
TI  - In Vitro Shock Absorption Tests on Implant-Supported Crowns: Influence of Crown
      Materials and Luting Agents.
AB  - PURPOSE: To investigate the force absorption capacity of implant-supported crowns
      made of different restorative materials and connected to abutments with different
      luting agents. MATERIALS AND METHODS: Molar crowns were milled of different
      computer-aided design/computer-aided manufacture materials (n = 8 crowns per
      material): polymethyl methacrylate, polyether ether ketone, composite, lithium
      disilicate, titanium, and zirconia. Crowns were mounted on titanium implant
      replicas using different luting agents: uncemented, temporarily cemented (zinc
      oxide-eugenol cement), conventionally cemented (zinc oxide phosphate cement), and
      adhesively bonded. As a reference, one implant replica was tested without a
      crown. Force absorptions of the different combinations of crown materials and
      luting agents were determined by applying an increasing force (0 to 250 N) on the
      occlusal crown surface and measuring the resulting force below the implant. Mean
      curves of applied and resulting forces up to 200 N were determined (six
      measurements per group), and slopes were calculated. Statistical analysis was
      performed (one-way analysis of variance, Bonferroni post hoc test, alpha = .05).
      RESULTS: Significant (P < .001) differences in the applied and resulting forces
      were found between the crown materials that were uncemented, temporarily
      cemented, cemented, and adhesively bonded. Materials with higher moduli of
      elasticity (ceramics, titanium) showed steeper slopes of the force curves and
      lower shock-absorbing capacity than resin-based materials, but were influenced
      more by the luting agents. The damping effects of resin-based materials were
      higher in combination with all cementation and luting modes. CONCLUSION: Shock
      absorption tests exhibited a strong material-dependent damping behavior of
      implant-supported crowns. The shock-absorbing capacity of crown materials with
      high moduli of elasticity may benefit from conventional cementation.

PMID- 28518189
TI  - Structure and dynamics of water confined in a graphene nanochannel under
      gigapascal high pressure: dependence of friction on pressure and confinement.
AB  - Recently, water flow confined in nanochannels has become an interesting topic due
      to its unique properties and potential applications in nanofluidic devices. The
      trapped water is predicted to experience high pressure in the gigapascal regime.
      Theoretical and experimental studies have reported various novel structures of
      the confined water under high pressure. However, the role of this high pressure
      on the dynamic properties of water has not been elucidated to date. In the
      present study, the structure evolution and interfacial friction behavior of water
      constrained in a graphene nanochannel were investigated via molecular dynamics
      simulations. Transitions of the confined water to different ice phases at room
      temperature were observed in the presence of lateral pressure at the gigapascal
      level. The friction coefficient at the water/graphene interface was found to be
      dependent on the lateral pressure and nanochannel height. Further theoretical
      analyses indicate that the pressure dependence of friction is related to the
      pressure-induced change in the structure of water and the confinement dependence
      results from the variation in the water/graphene interaction energy barrier.
      These findings provide a basic understanding of the dynamics of the nanoconfined
      water, which is crucial in both fundamental and applied science.

PMID- 28518188
TI  - pH-Dependent absorption spectrum of a protein: a minimal electrostatic model of
      Anabaena sensory rhodopsin.
AB  - A minimal electrostatic model is introduced which aims at reproducing and
      analyzing the visible-light absorption energy shift of a protein with pH. It
      relies on the existence of a protein structure, the prediction of titratable
      amino-acid pKa values and a very limited set of parameters. Applied to the case
      of the photochromic Anabaena sensory rhodopsin protein, the model succeeds in
      reproducing qualitatively the reported experimental data, confirming the
      importance of aspartic acid 217 in the observed blue shift in the lambdamax of
      ASR at neutral pH. It also suggests for the first time the role of two other
      amino acids, glutamic acid 36 at basic pH and aspartic acid 120 at acidic pH.

PMID- 28518190
TI  - Sequential incorporation of metallic cations (Cd2+ and Hg2+) and N-octylamine
      into titanium phosphate nanoparticles and their subsequent release in acid media.
AB  - Titanium phosphate nanoparticles, TPNP, consisting of a NaTi2(PO4)3 core and a
      shell of hydrogen phosphate and dihydrogen phosphate of titanium, undergo fast
      hydrolysis in water releasing phosphoric acid. This reaction is inhibited in the
      presence of metallic ions like Cd2+ or Hg2+, which are able to replace the
      protons of the shell acid phosphates. The amount of the adsorbed metallic cations
      could be regulated using counterions of different basicity. The resulting
      nanoparticles also incorporate NH2(CH2)7CH3 (N-octylamine) at room temperature
      forming N-octylammonium/phosphate ion pairs, but it was found that at higher
      cation concentration inside the nanoparticle, a lower amount of amine was
      adsorbed. The metallic cations and N-octylamine are released in acid media, but
      the starting material is not fully recovered.

PMID- 28518191
TI  - LaTiO2N-LaCrO3: continuous solid solutions towards enhanced photocatalytic H2
      evolution under visible-light irradiation.
AB  - (LaTiO2N)1-x(LaCrO3)x continuous solid solutions with an orthorhombic-phase ABX3
      perovskite structure and with varied LaCrO3 contents (0 <= x <= 1) were
      synthesized by a polymerized complex method followed by a post-treatment process
      of nitridation for the first time. Visible-light-driven photocatalytic H2
      evolution activities of the solid solutions gradually increased with the increase
      of x from 0.0 to 0.3, and then sharply decreased with the further increase of x
      from 0.3 to 1.0. With the increase of x, on the one hand, the narrowed bandgaps
      of solid solutions would enhance the generation of charge carriers and the
      increased lattice distortion of solid solutions could promote the separation and
      migration of charge carriers, thus mainly contributing to the improvement of
      photocatalytic activities; on the other hand, the lowered CBMs of solid solutions
      would reduce the driving force for reducing H2O to H2 and the decreased surface
      areas of solid solutions would weaken the adsorption of reactants and reduce the
      reactive sites, thereby resulting in the deterioration of photocatalytic
      activities.

PMID- 28518193
TI  - 4N electron aromatic cycles in polycyclic hydrocarbons.
AB  - Polycyclic fully conjugated hydrocarbons in which aromatics are fused to
      aromatics - or aromatics to antiaromatics - are important as potential organic
      semiconductors. Herein we explore the only remaining fusion pattern of
      antiaromatics to antiaromatics. It is shown computationally that the central
      antiaromatic unit (cyclobutadiene or pentalene) in such a three-unit polycyclic
      hydrocarbon, generated by fusion of three antiaromatic molecules, turns aromatic
      according to magnetic shielding (NICS) criteria. The resulting neutral 4N
      electron molecules possess a 4N pi electron perimeter with pronounced CC bond
      length equalization (as indicated by the HOMA geometric index) and significant
      aromatic stabilization energies (computed using the isomerization-stabilization
      method) and could be promising synthetic targets with small HOMO-LUMO gaps.

PMID- 28518192
TI  - Time-resolved signatures across the intramolecular response in substituted
      cyanine dyes.
AB  - The optically populated excited state wave packet propagates along
      multidimensional intramolecular coordinates soon after photoexcitation. This
      action occurs alongside an intermolecular response from the surrounding solvent.
      Disentangling the multidimensional convoluted signal enables the possibility to
      separate and understand the initial intramolecular relaxation pathways over the
      excited state potential energy surface. Here we track the initial excited state
      dynamics by measuring the fluorescence yield from the first excited state as a
      function of time delay between two color femtosecond pulses for several cyanine
      dyes having different substituents. We find that when the high frequency pulse
      precedes the low frequency one and for timescales up to 200 fs, the excited state
      population can be depleted through stimulated emission with efficiency that is
      dependent on the molecular electronic structure. A similar observation at even
      shorter times was made by scanning the chirp (frequencies ordering) of a
      femtosecond pulse. The changes in depletion reflect the rate at which the nuclear
      coordinates of the excited state leave the Franck-Condon (FC) region and progress
      towards achieving equilibrium. Through functional group substitution, we explore
      these dynamic changes as a function of dipolar change following photoexcitation.
      Density functional theory calculations were performed to provide greater insight
      into the experimental spectroscopic observations. Complete active space (CAS)
      self-consistent field and CAS second order perturbation theory calculated
      potential energy surfaces tracking twisting and pyramidalization confirm that the
      steeper potential at the FC region leads to the observation of faster wave packet
      dynamics.

PMID- 28518194
TI  - Detection of antibiotic resistant Escherichia Coli bacteria using infrared
      microscopy and advanced multivariate analysis.
AB  - Bacterial resistance to antibiotics is becoming a global health-care problem.
      Bacteria are involved in many diseases, and antibiotics have been the most
      effective treatment for them. It is essential to treat an infection with an
      antibiotic to which the infecting bacteria is sensitive; otherwise, the treatment
      is not effective and may lead to life-threatening progression of disease.
      Classical microbiology methods that are used for determination of bacterial
      susceptibility to antibiotics are time consuming, accounting for problematic
      delays in the administration of appropriate drugs. Infrared-absorption microscopy
      is a sensitive and rapid method, enabling the acquisition of biochemical
      information from cells at the molecular level. The combination of Fourier
      transform infrared (FTIR) microscopy with new statistical classification methods
      for spectral analysis has become a powerful technique, with the ability to detect
      structural molecular changes associated with resistivity of bacteria to
      antibiotics. It was possible to differentiate between isolates of Escherichia
      (E.) coli that were sensitive or resistant to different antibiotics with good
      accuracy. The objective computational classifier, based on infrared absorption
      spectra, is highly sensitive to the subtle infrared spectral changes that
      correlate with molecular changes associated with resistivity. These changes
      enable differentiating between the resistant and sensitive E. coli isolates
      within a few minutes, following the initial culture. This study provides proof-of
      concept evidence for the translational potential of this spectroscopic technique
      in the clinical management of bacterial infections, by characterizing and
      classifying antibiotic resistance in a much shorter time than possible with
      current standard laboratory methods.

PMID- 28518195
TI  - Integrated pretreatment and desalination by electrocoagulation (EC)-ion
      concentration polarization (ICP) hybrid.
AB  - Conventional water treatment process is composed of multiple stages, including
      desalination (salt removal) and pre/post-treatment of desalination to remove
      particles, chemicals, and other potential foulants for desalination. In this
      work, we developed a microfluidic proof-of-concept for a single device water
      treatment system, which removes both salt ions and non-salt contaminants. Our
      system combines electrocoagulation (EC), a versatile contaminant removal process,
      and ion concentration polarization (ICP) desalination, which is an
      electromembrane desalination process. We demonstrated a continuous EC-ICP
      operation that removed >95% of suspended solids and reduced the salinity from
      brackish range (20 mM NaCl) to a potable level (<8.6 mM NaCl). We also
      demonstrated that our system is flexible in terms of the type and concentration
      of contaminants it can handle. Combining two different electrochemical processes
      into a single system, we can reduce unnecessary voltage drop by having a shared
      anode, and achieve both seamless integration and energy efficient operation. Our
      system will find applications as a small-scale water treatment system, if
      properly scaled up in the future.

PMID- 28518198
TI  - Photophysical properties and excited state dynamics of 4,7-dithien-2-yl-2,1,3
      benzothiadiazole.
AB  - The relationships between the photophysics and structural properties of 4,7
      dithien-2-yl-2,1,3-benzothiadiazole as a function of solvent polarity are
      investigated both experimentally and by computational methods. Stationary
      fluorescence measurements are consistent with a model envisaging the presence of
      three types of conformers in equilibrium in the ground state. They are
      characterized by different relative orientations of the thiophene rings. Due to a
      low rotational barrier, the sample in solution is characterized by a distribution
      of relative internal orientations. By applying the Kawski method, we evaluate the
      average dipole moment of ground and excited states of the three types of
      conformers. The ground state dipole moments are small and similar for the three
      types of conformers. On the contrary, dipole moments differ substantially in the
      excited state. X-ray diffraction of a single crystal confirms the presence of an
      orientational disorder of thiophene rings. Transient absorption UV-visible
      spectroscopy experiments allows the identification of the main mechanisms
      responsible for the large Stokes shift observed in this push-pull molecule. Time
      dependent spectra provide a picture of the relaxation processes occurring after
      excitation: the primary step is an internal charge transfer assisted by thiophene
      ring planarization which occurs on a time scale ranging from 0.88 to 1.3
      picoseconds depending on solvent polarity. Moreover, time-resolved fluorescence
      measurements are consistent with a mechanism involving planarization accompanied
      by a stabilization of the charge transfer state as observed in polar solvents. In
      the latter, longer fluorescence lifetimes are observed along with a quantum yield
      decrease due to the activation of specific non-radiative relaxation channels. The
      photophysical behavior of 4,7-dithien-2-yl-2,1,3-benzothiadiazole in a solid
      matrix of polymethyl methacrylate is similar to that observed in solution, but
      the overall non-radiative process rate is slow with respect to that in the liquid
      phase. As a consequence, the radiative processes are enhanced giving rise to a
      fluorescence quantum yield of 90%. Such behavior is consistent with the proposed
      relaxation model.

PMID- 28518199
TI  - Cluster-based MOFs with accelerated chemical conversion of CO2 through C-C bond
      formation.
AB  - Investigations on metal-organic frameworks (MOFs) as direct catalysts have been
      well documented, but direct catalysis of the chemical conversion of terminal
      alkynes and CO2 as chemical feedstock by MOFs into valuable chemical products has
      never been reported. We report here two cluster-based MOFs I and II assembled
      from a multinuclear Gd-cluster and Cu-cluster, displaying high thermal and
      solvent stabilities. I and II as heterogeneous catalysts possess active catalytic
      centers [Cu12I12] and [Cu3I2], respectively, exhibiting excellent catalytic
      performance in the carboxylation reactions of CO2 with 14 kinds of terminal
      alkynes under 1 atm and mild conditions. For the first time catalysis of the
      carboxylation reaction of terminal alkynes with CO2 by MOF materials without any
      cocatalyst/additive is reported. This work not only reduces greenhouse gas
      emission but also provides highly valuable materials, opening a wide space in
      seeking recoverable catalysts to accelerate the chemical conversion of CO2.

PMID- 28518200
TI  - Multichromophoric hybrid species made of perylene bisimide derivatives and Ru(ii)
      and Os(ii) polypyridine subunits.
AB  - Herein, the synthesis and the photophysical and redox properties of a new
      perylene bisimide (PBI) species (L), bearing two 1,10-phenanthroline (phen)
      ligands at the two imide positions of the PBI, and its dinuclear Ru(ii) and
      Os(ii) complexes, [(bpy)2Ru(MU-L)Ru(bpy)2](PF6)4 (Ru2; bpy = 2,2'-bipyridine) and
      [(Me2-bpy)2Os(MU-L)Os(Me2-bpy)2](PF6)4 (Os2; Me2-bpy = (4,4'-dimethyl)-2,2'
      bipyridine), are reported. The absorption spectra of the compounds are dominated
      by the structured bands of the PBI subunit due to the lowest-energy spin-allowed
      pi-pi* transition. The spin-allowed MLCT transitions in Ru2 and Os2 are inferred
      by the absorption at 350-470 nm, where the PBI absorption is negligible. The
      absorption band extends towards the red region for Os2 due to the spin-forbidden
      MLCT transitions, intensified by the heavy osmium center. The reduction processes
      of the compounds are dominated by two successive mono-electronic PBI-based
      processes, which in the metal complexes are slightly shifted compared to the free
      ligand. On oxidation, both metal complexes undergo an apparent bi-electronic
      process (at 1.31 V vs. SCE for Ru2 and 0.77 V for Os2), attributed to the
      simultaneous one-electron oxidation of the two weakly-interacting metal centers.
      In Ru2 and Os2, the intense fluorescence of L subunit (lambdamax, 535 nm; tau,
      4.3 ns; Phi, 0.91) is fully quenched, mainly by photoinduced electron transfer
      from the metal centers, on the ps timescale (time constant, 11 ps in Ru2 and 3 ps
      in Os2). Such photoinduced electron transfer leads to the formation of a charge
      separated state, which directly decays to the ground state in about 70 ps in Os2,
      but produces the triplet pi-pi* state of the PBI subunit in 35 ps in Ru2. The
      results provide information on the excited-state processes of the hybrid species
      combining two dominant classes of chromophore/luminophore species, the PBI and
      the metal polypyridine complexes, and can be used for future design on new hybrid
      species with made-to-order properties.

PMID- 28518201
TI  - A general diastereoselective synthesis of highly functionalized ferrocenyl
      ambiphiles enabled on a large scale by electrochemical purification.
AB  - A general synthesis of highly functionalized ferrocenes, which include (P,B)- and
      (N,B)-ambiphiles, has been developed at a multigram scale. Diastereoselective
      stepwise modification of di-tert-butylated ferrocenes included the unprecedented
      separation of electroactive species. Bulky alkyl groups on ferrocenes ensure
      planar chirality of ambiphiles and enforce closer proximity of antagonist Lewis
      functions.

PMID- 28518202
TI  - Improved reactivity of a cyclic 13/15 compound by increased steric demand.
AB  - Herein we present the synthesis and characterization of the new four-membered
      Ga/P cycle [tBu2GaP(H)SitBu2Ph]2, which shows a cis/trans isomerization at
      ambient temperatures via a ring opening mechanism. The sterically demanding
      substituents on the phosphorus (-SitBu2Ph) and gallium (tBu) atoms lead to an
      unexpected reactivity towards bulky NHC ligands (IMes and IDipp). The resulting
      Lewis base stabilized monomeric 13/15 compounds feature an unusual binding mode
      of the carbene ligand. The ring opened state also enables a masked flp
      reactivity, which is shown by a reaction with the polar multiple bond in Ph-NCO.

PMID- 28518204
TI  - Integrated metabolomics and metallomics analyses in acute coronary syndrome
      patients.
AB  - Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality.
      Accurate risk prediction in ACS patients is critically important for helping
      clinicians make therapeutic decisions, such as recommending a more aggressive
      intervention and intensive follow-up. However, risk stratification in ACS
      patients remains challenging, and the identification of novel predictors is
      necessary for improving the prognostic prediction in ACS patients. We employed
      metallomics and untargeted metabolomics approaches to discover new biomarkers
      from the plasma samples of 20 ACS patients and 20 non-ACS patients. We identified
      metabolic changes related to lysophosphatidylcholines, caffeine, glycolysis,
      tryptophan and sphingomyelin metabolism (p value <0.05) that were perturbed in
      the ACS patients. Moreover, circulating metal elements, including Mg, Ca, K, Zn,
      Ni, Ga and In (p value <0.05), were altered in the ACS patients versus the
      controls. These changes suggest possible changes in cell membrane permeability
      and rigidity in ACS patients.

PMID- 28518205
TI  - Self-assembly of amphiphilic tripeptides with sequence-dependent nanostructure.
AB  - Supramolecular chemistry enables the creation of a diversity of nanostructures
      and materials. Many of these have been explored for applications as biomaterials
      and therapeutics. Among them, self-assembling peptides have been broadly applied.
      The structural diversity afforded from the library of amino acid building blocks
      has enabled control of emergent properties across length-scales. Here, we report
      on a family of amphiphilic tripeptides with sequence-controlled nanostructure. By
      altering one amino acid in these peptides, we can produce a diversity of
      nanostructures with different aspect-ratio and geometry. Peptides that produce
      high aspect-ratio structures can physically entangle to form hydrogels, which
      support cell viability in culture. Importantly, in comparison to many other short
      self-assembling peptide biomaterials, those reported here form filamentous
      nanostructures in the absence of typical secondary structures (i.e., beta-sheet).
      Thus, we have illustrated a facile way to obtain versatile biomaterials with
      different nanostructural morphology from short and defined peptide sequences.

PMID- 28518206
TI  - Organocatalytic hydroborylation promoted by N-heterocyclic olefins.
AB  - New complexes containing N-heterocyclic vinylene-stabilized [B2H5]+ fragments
      were prepared, and surprisingly it was found that the precursor N-heterocyclic
      olefins (NHOs) could promote the mild (room temperature) catalytic
      hydroborylation of ketones and aldehydes. This finding represents an important
      addition to the burgeoning field of non-metal mediated catalysis.

PMID- 28518207
TI  - Influence of particle size and dielectric environment on the dispersion behaviour
      and surface plasmon in nickel nanoparticles.
AB  - Nickel nanoparticles (NPs) are promising candidates for various applications,
      including biomedical ones, as they have good magnetic properties as well as high
      thermal conductivity. We used well-characterized Ni NPs of average Scherrer sizes
      from 1.31 nm to 22.23 nm and investigated the effects of the primary particle
      size, size distribution and dielectric environments, and of separately adding non
      ionic polyvinylpyrrolidone (PVP), cationic cetyltrimethylammonium bromide (CTAB)
      and anionic ethylenediaminetetraacetic acid (EDTA) in ethanol, on their stability
      and agglomeration behaviour using atomic force microscopy (AFM), particle size
      analysis and zeta potential study through dynamic light scattering (DLS) combined
      with UV-visible spectroscopy data. The dominant influence of surfactants,
      additives, particles size and shape on the surface plasmon resonance (SPR) was
      found. SPR is considerably sensitive to the dielectric environment in addition to
      size and shape. Moreover, increasing the concentration of PVP led to an enhanced
      SPR intensity and a shift in its position towards higher wavelength. 1.31 nm NPs
      with EDTA as an additive yielded the best dispersibility and also showed
      superparamagnetic behaviour at 300 K, indicating their favourable application
      potentials.

PMID- 28518210
TI  - Regular graveyard in the stronghold versus settlement burials in the bailey.
      Comparison of Early Medieval populations from Pohansko (Czech Republic).
AB  - ABSTRACT: The aim of the study is to identify possible differences in the
      prevalence of biological stress markers (cribra orbitalia, linear enammel
      hypoplasia), dental caries, activity markers (Schmorl's nodes) and markers of
      violence (traumatic lesions) in populations from a typical graveyard around the
      first church (9th-10th century AD) in the stronghold and from settlement burials
      in the southern bailey (second half of the 9th - beginning of the 10th century
      AD) of Slavs from Pohansko (Czech Republic). Cribra orbitalia and enamel
      hypoplasia did not markedly differ in either population. On the other hand, co
      occurrence of both markers was statistically different and distinction in higher
      age categories could indicate diverse living conditions. Lower cariousness in the
      population from the southern bailey was identified. The nature of postcranial
      traumatic lesions in both populations indicates rather their accidental origin.
      However, a higher incidence of cranial injuries points to more violent activities
      in the population from Pohansko compared to Mikulcice. A high number of healed
      face injuries in males from the southern bailey could indicate higher intragroup
      violence in this population.

PMID- 28518211
TI  - Inhibition of EGFR nuclear shuttling decreases irradiation resistance in HeLa
      cells.
AB  - INTRODUCTION: Cervical cancer is a leading cause of mortality in women worldwide.
      The resistance to irradiation at the advanced stage is the main reason for the
      poor prognosis and high mortality. This work aims to elucidate the molecular
      mechanism underlying the radio-resistance. MATERIAL AND METHODS: In this study,
      we determined the pEGFR-T654 and pDNA-PK-T2609 expression level changes in
      irradiated HeLa cells treated with T654 peptide, a nuclear localization signal
      (NLS) inhibitor, to inhibit EGFR nuclear transport. Cell viability, cell cycle
      and migratory capacity were analyzed. Xenograft animal model was used to evaluate
      the effect of EGFR nuclear transport inhibition on the tumor growth in vivo.
      RESULTS: The enhanced translocation of nuclear EGFR in the irradiated HeLa cells
      correlated with the increasing level of pEGFR-T654 and pDNA-PK-T2609. Inhibition
      of EGFR nuclear translocation by NLS peptide inhibitor attenuated DNA damage
      repair in the irradiated HeLa cells, decreased cell viability and promoted cell
      death through arrest at G0 phase. NLS peptide inhibitor impaired the migratory
      capacity of irradiated HeLa cells, and negatively affected tumorigenesis in
      xenograft mice. CONCLUSIONS: This work puts forward a potential molecular
      mechanism of the irradiation resistance in cervical cancer cells, providing a
      promising direction towards an efficient therapy of cervical cancer.

PMID- 28518212
TI  - Evaluation of cytotoxicity and pH changes generated by various dental pulp
      capping materials - an in vitro study.
AB  - INTRODUCTION: Various materials are used in direct dental pulp capping method.
      Their biocompatibility and alkalizing abilities are of primary importance
      affecting therapeutic effects. The aim of this study was to evaluate and compare
      the cytotoxicity of various pulp-capping materials on human gingival fibroblasts
      and investigate the pH changes induced by these materials. MATERIAL AND METHODS:
      Human gingival fibroblasts were cultured with nine direct pulp materials using
      culture plate inserts. The cytotoxic effects were recorded by using an MTT-based
      colorimetric assay after 3 and 24 h. In the second part of the experiment, the
      materials were inserted in dialysis tubes and transferred into plastic vials
      containing deionized water. The changes of the medium pH were measured after 3
      and 24 h. RESULTS: We showed differences in cell viability of gingival
      fibroblasts after varied time of exposition for the tested materials. Cell
      viability after 24 h increased for Dycal, Biopulp, and Calcipro, and decreased
      for Calcipulpe, Angelus, Angelus White, and ProRoot Regular. Cell viability for
      ProRoot and Life did not change. Non-setting calcium hydroxide preparations
      followed by the MTA group and setting calcium hydroxide materials produced the
      highest pH. All the tested materials significantly increased pH (p < 0.0001) at
      24 h. CONCLUSIONS: Currently used pulp capping materials varied in their
      cytotoxicity relative to human gingival fibroblasts and their alkalizing
      capacities. Since most likely pH does not affect the viability of cultured cells,
      further investigations are required to determine physicochemical properties of
      these materials and the biological activity of the dental pulp.

PMID- 28518213
TI  - Relationship between toll-like receptor 2 R753Q and T16934A polymorphisms and
      Staphylococcus aureus nasal carriage.
AB  - BACKGROUND: The association among specific single-nucleotide polymorphisms (SNPs)
      in TLR2 R753Q (rs5743708) and T16934A (rs4696480) and the nasal carriage of
      Staphylococcus aureus was studied in adults before CABG. METHODS: The TLR2
      polymorphisms were genotyped in 299 consecutive patients prepared for a CABG
      operation. Genotyping was performed using restriction fragment length
      polymorphism (RFLP) analysis of PCR-amplified fragments. Two nasal swab cultures
      were taken within 2 weeks before the operation. Subjects were classified as
      Staphylococcus aureus carriers if at least one culture was positive while those
      patients with both cultures found to be negative were classified as non-carriers.
      RESULTS: The prevalence of nasal S. aureus carriage in the final cohort was 22.1%
      (66/299), while no MRSA was detected in our study group. No significant
      differences in the TLR2 polymorphisms were observed between the study and the
      control groups. No associations were found between TLR2 haplotypes and the
      covariates of age, sex, NYHA, weight, height, BMI, CAD, smoking status and ESlog
      score. No differences were found between carriers and noncarriers regarding the
      allelic distribution of the TLR2 T-16934A SNP. Almost 93% of the patients who
      were screened for the presence of the TLR2 Arg753Gln (rs5743708) were GG wild
      type homozygous. Twenty one subjects from the study group (7.1%) were GA
      heterozygous, while no patient in either group was homozygous for the TLR2
      Arg753Gln (rs5743708) mutation. TLR2 Arg753Gln genotyping showed that GA
      heterozygous patients were detected more frequently in the group of
      Staphylococcus aureus nasal carriers than in non-carrier adults. CONCLUSION: Our
      results suggest that the carrier status for the GA variant of the TLR2 Arg753Gln
      (rs5743708) polymorphism may be a risk factor for Staphylococcus aureus carriage.

PMID- 28518215
TI  - The Toll-like receptor 9 signalling pathway regulates MR1-mediated bacterial
      antigen presentation in B cells.
AB  - Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a
      semi-invariant T-cell receptor (Valpha7.2 in humans and Valpha19 in mice). The
      development of MAIT cells requires the antigen-presenting MHC-related protein 1
      (MR1), as well as commensal bacteria. The mechanisms that regulate the functional
      expression of MR1 molecules and their loading with bacterial antigen in antigen
      presenting cells are largely unknown. We have found that treating B cells with
      the Toll-like receptor 9 (TLR9) agonist CpG increases MR1 surface expression.
      Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface
      expression. This is limited to B cells and not other types of cells such as
      monocytes, T or natural killer cells. Knocking-down TLR9 expression by short
      hairpin RNA reduces MR1 surface expression and MR1-mediated bacterial antigen
      presentation. CpG-A triggers early endosomal TLR9 activation, whereas CpG-B is
      responsible for late endosomal/lysosomal activation of TLR9. Consistently,
      blocking endoplasmic reticulum to Golgi protein transport, rather than lysosomal
      acidification, suppressed MR1 antigen presentation. Overall, our results indicate
      that early endosomal TLR9 activation is important for MR1-mediated bacterial
      antigen presentation.

PMID- 28518217
TI  - Impacts of an invasive plant are fundamentally altered by a co-occurring forest
      disturbance.
AB  - Invasive species frequently co-occur with other disturbances, which can impact
      the same ecosystem functions as the invader. Yet invasion studies rarely control
      for the presence of these other disturbances, although their overlapping effects
      may influence the direction and magnitude of impacts attributed to the invader
      alone. Here, we ask whether controlling for the presence of a co-occurring
      disturbance, as well as the time since disturbance, yields different values of an
      invader's ecosystem effects than when these factors remain unaddressed. We used a
      chronosequence of six forest stands at a single site: five logged stands that
      each contained paired invaded-uninvaded plots of the forest understory invasive
      grass Microstegium vimineum, as well as one unlogged and uninvaded control stand.
      By controlling for the presence of both logging and invasion, we untangled the
      effects of each through time. We found that the co-occurring disturbance of
      logging can dramatically alter the measured effects of M. vimineum by amplifying,
      dampening, negating, or entirely reversing the direction of the invader's
      impacts. During its period of peak impact, logging amplified the invader's
      positive effect on the size of the soil microbial biomass pool by 24%, reduced
      the invader's positive effect on soil water holding capacity by 5%, negated the
      invader's positive effect on the particulate organic matter carbon pool (from a
      9% increase to no significant effect), and reversed the direction of the
      invader's impact on net nitrogen mineralization rate from a 51% increase to a 52%
      decrease. Furthermore, the influence of logging on the invader's impacts was not
      static, but dynamic through time. The results from our site therefore demonstrate
      that failure to account for the impacts of a co-occurring disturbance, as well as
      the time since disturbance, can result in flawed inference about the nature of an
      invader's effects. Future research should determine how widespread such flawed
      inference might be among other invasive species and across different
      environmental contexts. To help guide such research, we describe a general
      framework for disentangling the overlapping effects of invasions and co-occurring
      disturbances through time.

PMID- 28518216
TI  - Queen presence mediates the relationship between collective behaviour and disease
      susceptibility in ant colonies.
AB  - The success of social living can be explained, in part, by a group's ability to
      execute collective behaviours unachievable by solitary individuals. However,
      groups vary in their ability to execute these complex behaviours, often because
      they vary in their phenotypic composition. Group membership changes over time due
      to mortality or emigration, potentially leaving groups vulnerable to ecological
      challenges in times of flux. In some societies, the loss of important individuals
      (e.g. leaders, elites and queens) may have an especially detrimental effect on
      groups' ability to deal with these challenges. Here, we test whether the removal
      of queens in colonies of the acorn ant Temnothorax curvispinosus alters their
      ability to execute important collective behaviours and survive outbreaks of a
      generalist entomopathogen. We employed a split-colony design where one half of a
      colony was maintained with its queen, while the other half was separated from the
      queen. We then tested these subcolonies' performance in a series of collective
      behaviour assays and finally exposed colonies to the entomopathogenic fungus
      Metarhizium robertsii by exposing two individuals from the colony and then
      sealing them back into the nest. We found that queenright subcolonies
      outperformed their queenless counterparts in nearly all collective behaviours.
      Queenless subcolonies were also more vulnerable to mortality from disease.
      However, queenless groups that displayed more interactions with brood experienced
      greater survivorship, a trend not present in queenright subcolonies. Queenless
      subcolonies that engage in more brood interactions may have had more resources
      available to cope with two physiological challenges (ovarian development after
      queen loss and immune activation after pathogen exposure). Our results indicate
      that queen presence can play an integral role in colony behaviour, survivorship
      and their relationship. They also suggest that interactions between workers and
      brood are integral to colonies survival. Overall, a social group's history of
      social reorganization may have strong consequences on their collective behaviours
      and their vulnerability to disease outbreaks.

PMID- 28518218
TI  - Comparison and optimization of in silico algorithms for predicting the
      pathogenicity of sodium channel variants in epilepsy.
AB  - OBJECTIVE: Variants in neuronal voltage-gated sodium channel alpha-subunits genes
      SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and
      other autosomal dominant childhood epilepsy syndromes. However, in clinical
      practice, missense variants are often classified as variants of uncertain
      significance when missense variants are identified but heritability cannot be
      determined. Genetic testing reports often include results of computational tests
      to estimate pathogenicity and the frequency of that variant in population-based
      databases. The objective of this work was to enhance clinicians' understanding of
      results by (1) determining how effectively computational algorithms predict
      epileptogenicity of sodium channel (SCN) missense variants; (2) optimizing their
      predictive capabilities; and (3) determining if epilepsy-associated SCN variants
      are present in population-based databases. This will help clinicians better
      understand the results of indeterminate SCN test results in people with epilepsy.
      METHODS: Pathogenic, likely pathogenic, and benign variants in SCNs were
      identified using databases of sodium channel variants. Benign variants were also
      identified from population-based databases. Eight algorithms commonly used to
      predict pathogenicity were compared. In addition, logistic regression was used to
      determine if a combination of algorithms could better predict pathogenicity.
      RESULTS: Based on American College of Medical Genetic Criteria, 440 variants were
      classified as pathogenic or likely pathogenic and 84 were classified as benign or
      likely benign. Twenty-eight variants previously associated with epilepsy were
      present in population-based gene databases. The output provided by most
      computational algorithms had a high sensitivity but low specificity with an
      accuracy of 0.52-0.77. Accuracy could be improved by adjusting the threshold for
      pathogenicity. Using this adjustment, the Mendelian Clinically Applicable
      Pathogenicity (M-CAP) algorithm had an accuracy of 0.90 and a combination of
      algorithms increased the accuracy to 0.92. SIGNIFICANCE: Potentially pathogenic
      variants are present in population-based sources. Most computational algorithms
      overestimate pathogenicity; however, a weighted combination of several algorithms
      increased classification accuracy to >0.90.

PMID- 28518214
TI  - Immune monitoring as prerequisite for transplantation tolerance trials.
AB  - Ever since its first application in clinical medicine, scientists have been urged
      to induce tolerance towards foreign allogeneic transplants and thus avoid
      rejection by the recipient's immune system. This would circumvent chronic use of
      immunosuppressive drugs (IS) and thus avoid development of IS-induced side
      effects, which are contributing to the still unsatisfactory long-term graft and
      patient survival after solid organ transplantation. Although manifold strategies
      of tolerance induction have been described in preclinical models, only three
      therapeutic approaches have been utilized successfully in a still small number of
      patients. These approaches are based on (i) IS withdrawal in spontaneous
      operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and
      (iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing
      these approaches show that tolerance induction does not work in all patients.
      Thus, there is a need for reliable biomarkers, which can be used for patient
      selection and post-therapeutic immune monitoring of safety, success and failure.
      In this review, we summarize recent achievements in the identification and
      validation of such immunological assays and biomarkers, focusing mainly on kidney
      and liver transplantation. From the published findings so far, it has become
      clear that indicative biomarkers may vary between different therapeutic
      approaches applied and organs transplanted. Also, patient numbers studied so far
      are very small. This is the main reason why nearly all described parameters lack
      validation and reproducibility testing in large clinical trials, and are
      therefore not yet suitable for clinical practice.

PMID- 28518220
TI  - Postdonation iron replacement for maintaining iron stores in female whole blood
      donors in routine donor practice: results of two feasibility studies in
      Australia.
AB  - BACKGROUND: Iron deficiency represents a risk to donor health and the blood
      supply. Efficacy trials indicate that postdonation iron replacement improves iron
      stores but they do not account for complexities of implementation in the routine
      collection context. We therefore conducted two prospective feasibility studies in
      Australian donor centers. STUDY DESIGN AND METHODS: In both studies we recruited
      female donors between 18 and 45 years who had made at least one donation in the
      previous 12 months. In READ (replacement advice), female donors were given a
      recommendation to self-procure postdonation iron. In DIRECT (donor iron
      replacement), donors were provided with a course of iron supplements. Donors
      could return to donate at their discretion and were surveyed after the
      recruitment visit and again toward the end of the 13-month follow-up. Donor
      uptake, adverse effects, effectiveness in maintaining iron stores, and workflow
      impact were assessed. RESULTS: We recruited 1404 (70.9% of invited) donors to
      READ and 768 (53.2% of invited) to DIRECT. READ and DIRECT extended predonation
      interviews by 1 and 5 minutes, respectively. Among participants, 44 and 88% took
      iron in READ and DIRECT, respectively. Adverse effects were common but usually
      mild. READ failed to maintain iron stores in the population, but was effective in
      donors who consumed more than 75% of the recommended dose. DIRECT was effective
      in preventing declines in ferritin concentration. CONCLUSION: Trade-offs between
      cost, complexity, uptake, and effectiveness must be considered in the
      implementation of postdonation iron supplementation.

PMID- 28518219
TI  - Impact of the timing of hepatitis B virus identification and anti-hepatitis B
      virus therapy initiation on the risk of adverse liver outcomes for patients
      receiving cancer therapy.
AB  - BACKGROUND: Data on the incidence of adverse liver outcomes are limited for
      cancer patients with chronic (hepatitis B surface antigen [HBsAg]
      positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg
      negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This
      study was aimed at determining the impact of test timing and anti-HBV therapy on
      adverse liver outcomes in these patients. METHODS: Patients with solid or
      hematologic malignancies who received chemotherapy between 2004 and 2011 were
      retrospectively studied. HBV testing and anti-HBV therapy were defined as early
      at the initiation of cancer therapy and as late after initiation. Outcomes
      included hepatitis flares, hepatic impairment, liver failure, and death. Time-to
      event analysis was used to determine incidence, and multivariate hazard models
      were used to determine predictors of outcomes. RESULTS: There were 18,688 study
      patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of
      4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with
      solid tumors, late identification of chronic HBV was associated with a higher
      risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI],
      1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure
      (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in
      comparison with early identification. Among patients with hematologic
      malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27)
      times higher for persons with late initiation of anti-HBV therapy versus early
      initiation. Patients with late identification of chronic HBV had late or no anti
      HBV therapy. Chronic HBV predicted liver failure in patients with solid or
      hematologic malignancies, whereas male sex and late identification were
      predictors for patients with solid tumors. CONCLUSIONS: Early identification
      correlates with early anti-HBV therapy and reduces the risk of liver failure and
      death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76.
      (c) 2017 American Cancer Society.

PMID- 28518225
TI  - MO-F-BRA-01: A Biomechanical Constraint for Intensity-Driven Deformable Alignment
      of Skeletal Components in the Head and Neck Region.
AB  - PURPOSE: To introduce a biomechanical constraint into an intensity-based
      deformable image registration (DIR) method in order to limit nonphysical
      deformations of skeletal components in the neck region. METHODS: On the reference
      image, vertebral bodies were segmented. A penalty term, based on the differences
      in squared inter-voxel distances within each vertebra before and after
      deformation, was introduced into a routinely used (ITK) intensity-based B-spline
      alignment algorithm. To assess accuracy, deformable image registration was
      performed on five pairs of cone-beam CT scans of a head and neck cancer patient.
      Surface registrations of individual vertebrae established their true
      displacements (translations and rotations). Orthogonal Procrustes analysis of
      transformed points within each vertebra established the estimated rotations and
      translations from the resultant deformation vector fields with and without the
      penalty term. RESULTS: The registration errors across all points within the
      vertebrae with the penalty term (0.2+/-0.2, 0.2+/-0.2, 0.3+/-0.2) [mm] were
      significantly lower than without (2.8+/-2.6, 3.2+/-2.9, 2.8+/-3.0) [mm],
      indicating that employing the penalty term successfully restricted local
      deformation in the region of the cervical vertebrae. The errors of the bulk
      translations and rotations of individual vertebrae were similarly reduced: (0.7+/
      0.4, 0.9+/-0.7, 0.5+/-0.4) to (O.1+/-0.1, 0.l+0.1, 0.2+/-0.2) [mm] for
      translation and (3.4+/-2.6, 1.3+/-1.1, 1.4+/-1.1) to (0.7+/-0.6, 0.3+/-0.2, 0.3+/
      0.3) [ degrees ] for rotation. CONCLUSIONS: The introduction of a local rigidity
      penalty improved the integrity of skeletal alignment under neck articulation.
      Further research will explore biomechanical penalties that will more
      realistically constrain the changes of other tissues (e.g. muscles) in the neck
      region. Supported by NIHR01CA59827.

PMID- 28518223
TI  - Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO
      pathway.
AB  - Reactive oxygen species (ROS) contribute to many aspects of physiological and
      pathological cardiovascular processes. However, the underlying mechanism of ROS
      induction by low shear stress (LSS) remains unclear. Accumulating evidence has
      shown that the angiotensin II type 1 receptor (AT1R) is involved in inflammation,
      apoptosis, and ROS production. Our aim was to explore the role of AT1R in LSS
      mediated ROS induction. We exposed human umbilical vein endothelial cells
      (HUVECs) to LSS (3 dyn/cm2 ) for different periods of time. Western blotting and
      immunofluorescence showed that LSS significantly induced AT1R expression in a
      time-dependent manner. Using immunohistochemistry, we also noted a similar
      increase in AT1R expression in the inner curvature of the aortic arch compared to
      the descending aorta in C57BL/6 mice. Additionally, HUVECs were cultured with a
      fluorescent probe, either DCFH, DHE or DAF, after being subjected to LSS. Cell
      chemiluminescence and flow cytometry results revealed that LSS stimulated ROS
      levels and suppressed nitric oxide (NO) generation in a time-dependent manner,
      which was reversed by the AT1R antagonist Losartan. We also found that Losartan
      markedly increased endothelial NO synthase (eNOS) phosphorylation at
      Ser(633,1177) and dephosphorylation at Thr(495), which involved AKT and ERK.
      Moreover, the ROS level was significantly reduced by endogenous and exogenous NO
      donors (L-arginine, SNP) and increased by the eNOS inhibitor L-NAME. Overall, we
      conclude that LSS induces ROS via AT1R/eNOS/NO.

PMID- 28518222
TI  - The effect of initial molecular profile on response to recombinant interferon
      alpha (rIFNalpha) treatment in early myelofibrosis.
AB  - BACKGROUND: Although recombinant interferon-alpha (rIFNalpha) effectively treats
      patients with early myelofibrosis, the effect of driver and high molecular risk
      (HMR) mutations has not been considered. In this phase 2 study, for the first
      time, the authors correlate response to rIFNalpha treatment with driver and HMR
      mutations. METHODS: Patients were diagnosed using World Health Organization or
      International Working Group for Myeloproliferative Neoplasms Research and
      Treatment criteria. Only patients who had low or intermediate-1 Dynamic
      International Prognostic Scoring System scores with >=15% hematopoietic bone
      marrow foci were included. History, symptom assessment, physical examination, and
      blood and bone marrow studies were performed. Genomic DNA was extracted from
      frozen cells, and next-generation targeted sequencing of 45 genes was performed.
      Either rIFNalpha-2b (0.5 million units subcutaneously 3 times weekly) or
      pegylated rIFNalpha-2a (45 MUg weekly) with escalation was initiated. All
      patients were followed at the authors' institution, and regular bone marrow
      biopsies were encouraged. International Working Group for Myeloproliferative
      Neoplasms Research and Treatment and European LeukemiaNet treatment response
      criteria were used. RESULTS: Of 30 patients (16 women and 14 men; median age, 58
      years), 22 were classified as low risk, and 8 were classified as intermediate-1
      risk. Two patients achieved complete remission, 9 achieved partial remission, 4
      had clinical improvement, 7 had stable disease; 3 had progressive disease, 1
      relapsed, and 4 died. There were 22 patients with JAK mutations, 6 with CALR
      mutations, and 2 with MPL mutations. Seventy-three percent of patients improved
      or remained stable with acceptable toxicity, including 37% who achieved complete
      or partial remission. There was no correlation between treatment response and
      baseline driver mutations or Dynamic International Prognostic Scoring System
      scores. Of 8 poor responders, 3 had ASXL1 or SRSF2 mutations. CONCLUSIONS: Early
      treatment with rIFNalpha in patients without HMR mutations may prevent the
      development of marked splenomegaly, anemia, and florid myelofibrosis. Molecular
      profiling at the time of diagnosis may predict prognosis and treatment response.
      Cancer 2017;123:2680-87. (c) 2017 American Cancer Society.

PMID- 28518226
TI  - MO-E-211-01: ABR 2014: Trained for Competence.
AB  - : Medical physicists are the only non-physician professionals recognized by the
      American Board of Medical Specialties through certification by the American Board
      of Radiology (ABR). The ABR has always set high standards of clinical competency
      and now with the endorsement of the AAPM, is able to raise these standards by
      mandating that in 2014, to sit as a candidate for board certification, enrollment
      in an accredited physics residency program is required. This is an enormous step
      to elevate our profession, as now we have the means to specify only one method
      for achieving board certification that is through an accredited residency
      program, which leads to an increase of clinical competency. This will have a
      positive impact on our profession's recognition. Most challenges have been met,
      namely the number of residency positions has increased exponentially to meet the
      manpower needs. In addition, funding mechanisms are being sought for government
      support of such training programs. However, we have to ensure that pathways for a
      residency and certification do not eliminate strong scientists; if for example,
      they do not have the prior educational pre-requisite. Our profession has always,
      and must continue to breed strong scientists who have clinical expertise though
      may not be seeking a clinical career. This requires developing skill sets that
      prepare scientists to be researchers or residents who can perform research. We
      will discuss the benefits of the 2014 mandate along with the challenges that
      still exist. LEARNING OBJECTIVES: 1. The ABR requirements c2014: Why they're
      needed and how they were established 2. Physics Residency Programs: Importance
      for our profession and methods to fund 3. Essential elements for competency:
      didactic, scientific and clinical.

PMID- 28518227
TI  - MO-F-BRCD-02: SBRT (Part 2): Physics and Quality Assurance Updates.
AB  - The technical advantage of stereotactic body radiation therapy (SBRT) is based
      upon the ability to deliver a hypofractionated course of heterogeneous dose to a
      well-defined volume with a rapid fall-off of dose outside the treatment volume.
      The overall goal is to deliver an ablative dose to the target while minimizing
      the effects of radiation on the surrounding normal tissue. The major advantage of
      SBRT is the greater biologically effective dose to the target than that permitted
      by less conformal, fractionated techniques. In this presentation the established
      recommendations for quality assurance and safety of SBRT from ACR, ASTRO, and
      AAPM will be reviewed. The recommendations include establishing an SBRT clinic,
      equipment and imaging considerations, overview of staffing and personnel
      qualifications, treatment planning considerations, training, acceptance and
      commissioning practices, and use of safety checklists. Additionally, a Failure
      Mode and Effect Analysis (FMEA) for Stereotactic Body Radiation Therapy Delivery
      is presented. References: 1. Timothy D. Solberg PhD, James M. Balter PhD, Stanley
      H. Benedict PhD, Benedick A. Fraass PhD, Brian Kavanagh MD, Curtis Miyamoto MD,
      Todd Pawlicki PhD, Louis Potters MD, Yoshiya Yamada MD, "Quality and safety
      considerations in stereotactic radiosurgery and stereotactic body radiation
      therapy" Practical Radiation Oncology (2011)2. Benedict SH, Yenice KM, Followill
      D, et al., "Stereotactic Body Radiation Therapy: The Report of AAPM Task Group
      101" Med Phys. 2010;37:4078- 41013. Potters L, Kavanagh B, Galvin JM, et al.
      American Society for Therapeutic Radiology and Oncology (ASTRO) and American
      College of Radiology (ACR) practice guideline for the performance of stereotactic
      body radiation therapy. Int J Radiat Oncol Biol Phys. 2010;76:326-3324. Julian R.
      Perks PhD, Sinisa Stanic MD, Robin L Stern PhD, Barbara Henk RN MSN, Marsha S
      Nelson RN MBA, Rick D Harse RTT, Mathew Mathai BS CMD, James A Purdy PhD, Richard
      K Valicenti MD MA, Allan D Siefkin MD and Allen M Chen MD, "Failure Mode and
      Effect Analysis for Stereotactic Body Radiation Therapy Delivery" Int J Radiat
      Oncol Biol Phys. 2012 (in press) Learning Objectives: 1. Review and understand
      the ASTRO Recommendations for QA and Safety with SBRT 2. Review and understand
      the AAPM Task Group Recommendations for SBRT 3. Review and understand a FEMA
      Analysis of SBRT.

PMID- 28518224
TI  - T helper type 1-related molecules as well as interleukin-15 are hyperexpressed in
      the skin lesions of patients with pyoderma gangrenosum.
AB  - Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into
      the group of neutrophilic dermatoses. Although a number of studies confirmed the
      central role of innate immunity, only few studies have investigated the possible
      contributing role of acquired immunity. In particular, no reports concerning T
      helper type 1 (Th1) and Th2 cells are available as yet. Therefore, 15 patients
      with PG, five with Sweet's syndrome (SS) and nine skin specimens from healthy
      controls (HC) were investigated, evaluating the expression of Th1-related markers
      interleukin (IL)-12, interferon (IFN)-gamma, C-X-C motif chemokine receptor 3
      (CXCR3) and C-C motif chemokine receptor 5 (CCR5), of the Th2-related molecules
      IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40 ligand, of IL-15
      and the natural killer (NK) cell marker CD56 in skin lesions by
      immunohistochemistry. Patients with PG and SS showed a higher expression of Th1
      markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous
      in PG skin lesions compared to SS (P = 0.0157 and < 0.0001, respectively). Both
      CD40 and CD40L were expressed more in PG than in SS and HC (P < 0.0001 for both).
      Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients
      with PG than in those of SS and HC (P < 0.0001 for both). Our results suggest
      that Th2 cells are down-regulated in PG. At the same time, over-expression of the
      co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance.
      Both these findings might explain the most aggressive behaviour of PG in
      comparison to SS. Moreover, over-expression of IL-15+ and CD56+ cells may suggest
      a possible role of NK cells in the pathogenesis of the disease.

PMID- 28518221
TI  - Micronutrient supplementation in adults with HIV infection.
AB  - BACKGROUND: Micronutrient deficiencies are common among adults living with HIV
      disease, particularly in low-income settings where the diet may be low in
      essential vitamins and minerals. Some micronutrients play critical roles in
      maintenance of the immune system, and routine supplementation could therefore be
      beneficial. This is an update of a Cochrane Review previously published in 2010.
      OBJECTIVES: To assess whether micronutrient supplements are effective and safe in
      reducing mortality and HIV-related morbidity of HIV-positive adults (excluding
      pregnant women). SEARCH METHODS: We performed literature searches from January
      2010 to 18 November 2016 for new randomized controlled trials (RCTs) of
      micronutrient supplements since the previous review included all trials
      identified from searches prior to 2010. We searched the CENTRAL (the Cochrane
      Library), Embase, and PubMed databases. Also we checked the World Health
      Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and
      the ClinicalTrials.gov trials registers. We also checked the reference lists of
      all new included trials. SELECTION CRITERIA: We included RCTs that compared
      supplements that contained either single, dual, or multiple micronutrients with
      placebo, no treatment, or other supplements. We excluded studies that were
      primarily designed to investigate the role of micronutrients for the treatment of
      HIV-positive participants with metabolic morbidity related to highly active
      antiretroviral therapy (HAART). Primary outcomes included all-cause mortality,
      morbidity, and disease progression. DATA COLLECTION AND ANALYSIS: Two review
      authors independently selected trials for inclusion, and appraised trial quality
      for risk of bias. Where possible, we presented results as risk ratios (RR) for
      dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean
      differences (MD) for continuous variables, each with 95% confidence intervals
      (CIs). Since we were often unable to pool the outcome data, we tabulated it for
      each comparison. We assessed the certainty of the evidence using the GRADE
      approach. MAIN RESULTS: We included 33 trials with 10,325 participants, of which
      17 trials were new trials. Ten trials compared a daily multiple micronutrient
      supplement to placebo in doses up to 20 times the dietary reference intake, and
      one trial compared a daily standard dose with a high daily dose of multivitamins.
      Nineteen trials compared supplementation with single or dual micronutrients (such
      as vitamins A and D, zinc, and selenium) to placebo, and three trials compared
      different dosages or combinations of micronutrients. Multiple micronutrientsWe
      conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials,
      1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400
      participants), and ART-naive adults with concurrent active tuberculosis (3
      trials, 1429 participants). Routine multiple micronutrient supplementation may
      have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI
      0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine
      supplementation for up to two years may have little or no effect on the average
      of mean CD4+ cell count (MD 26.40 cells/mm3, 95% CI -22.91 to 75.70; 6 trials,
      1581 participants, low certainty evidence), or the average of mean viral load (MD
      -0.1 log10viral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants,
      moderate certainty evidence). One additional trial in ART-naive adults did report
      an increase in the time to reach a CD4+ cell count < 250 cells/mm3 after two
      years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1
      trial, 439 participants). However, the trial authors reported this effect only in
      the trial arm that received multiple micronutrients plus selenium (not either
      supplementation alone), which is inconsistent with the findings of other trials
      that used similar combinations of micronutrients and selenium.In one additional
      trial that compared high-dose multiple micronutrient supplementation with
      standard doses in people on ART, peripheral neuropathy was lower with high dose
      supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI
      0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to
      increased adverse events (elevated alanine transaminase (ALT) levels) in the high
      dose group. Single or dual micronutrientsNone of the trials of single or dual
      micronutrient supplements were adequately powered to assess for effects on
      mortality or morbidity outcomes. No clinically significant changes in CD4 cell
      count (data not pooled, 14 trials, 2370 participants, very low or low certainty
      evidence) or viral load (data not pooled, seven studies, 1334 participants, very
      low or low certainty evidence), were reported. Supplementation probably does
      increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D:
      4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty
      evidence) and may also increase blood concentrations of vitamin A (data not
      pooled, 3 trials, 495 participants, low certainty evidence), especially in those
      who are deficient. AUTHORS' CONCLUSIONS: The analyses of the available trials
      have not revealed consistent clinically important benefits with routine multiple
      micronutrient supplementation in people living with HIV. Larger trials might
      reveal small but important effects.These findings should not be interpreted as a
      reason to deny micronutrient supplements for people living with HIV where
      specific deficiencies are found or where the person's diet is insufficient to
      meet the recommended daily allowance of vitamins and minerals.

PMID- 28518228
TI  - MO-F-BRA-05: Real-Time 3D Tumor Localization for Lung IGRT Using a Single X-Ray
      Projection.
AB  - PURPOSE: To study the feasibility of a novel 2D/3D image registration method,
      called Projection Metric Learning for Shape Kernel Regression (PML-SKR), in
      supporting on-board x-ray imaging systems to perform real-time image-guided
      radiation therapy in the lung. METHODS: PML-SKR works in two stages: planning and
      treatment. At planning stage, firstly it parameterizes the patient's respiratory
      deformation from the patient's treatment-planning Respiratory-Correlated CTs
      (RCCTs) by doing PCA analysis on the inter-phase respiratory deformations.
      Secondly, it simulates a set of training projection images from a set of deformed
      CTs where their associated deformation parameters are sampled within 3 standard
      deviations of the parameter's values observed in the RCCTs. Finally, it learns a
      Riemannian distance metric on projection intensity for each deformation
      parameter. The learned distance metric forms a Gaussian kernel of a kernel
      regression that minimizes the leave-one-out regression residual of the
      corresponding deformation parameter. At treatment stage, PML-SKR interpolates the
      patient's 3D deformation parameters from the parameter's values in the training
      cases using the kernel regression with the learned distance metrics. RESULTS: We
      tested PML-SKR on the NST (Nanotube Stationary Tomosynthesis) x-ray imaging
      system. In each test case, a DRR (dimension: 64*64) of an x-ray source in the NST
      was simulated from a target CT for registration. The target CTs were deformed by
      normally distributed random samples of the first three deformation parameters. We
      generated 300 synthetic test cases from 3 lung datasets and measured the
      registration quality by the mTRE (mean Target Registration Error) over all cases
      and all voxels at tumor sites. With PML-SKR's registrations, the average mTRE and
      its standard deviation are down from 10.89+/-4.44 to 0.67+/-0.46 mm using 125
      training projection images. The computation time for each registration is 12.71+/
      0.70 ms. CONCLUSION: The synthetic results have shown PML-SKR's promise in
      supporting real-time, accurate, and low-dose lung IGRT. This work was partially
      supported by Siemens Medical Solutions.

PMID- 28518229
TI  - MO-D-BRB-09: Treatment Delivery QA for Online Adaptive Radiation Therapy Based on
      Dynamic Machine Information (DMI): A Feasibility Study.
AB  - PURPOSE: To implement a quality assurance (QA) system for the treatment delivery
      of online adaptive radiation therapy utilizing Dynamic Machine Information (DMI).
      MATERIALS AND METHODS: DMI provides the expected/actual MLC leaf-positions,
      delivered MU, and beam-on status every 50ms during delivery. In this study a
      stream of DMI inputs is simulated by playing back Dynalog information recorded
      while delivering a test fluence map (FM). Based on these DMI inputs, the QA
      system performs three levels of monitoring/verification on the plan delivery
      process: (1) Following each input, actual and expected FMs delivered up to the
      current MLC position is dynamically updated using corresponding MLC positions in
      the DMI. The magnitude and frequency of pixel-by-pixel fluence differences
      between these two FMs are calculated and visualized in histograms.(2) At each
      control point, actual MLC positions are verified against the treatment plan for
      potential errors in data transfer between the treatment planning system (TPS) and
      the MLC controller.(3) Both (1) and (2) can signal beam-hold with a user
      specified error tolerance.(4) After treatment, delivered dose is reconstructed in
      TPS based on DMI data during delivery, and compared to planned dose. RESULTS: (1)
      Efficiency: Average latency from DMI input to the completion of fluence
      difference calculation is <1ms.(2) Efficacy: For test FM, transient error in leaf
      positions is (-0.07+/-0.28)mm; cumulative errors in delivered fluence is (0.003+/
      0.183)% of the maximal fluence. The system can also identify data transfer errors
      between TPS and MLC controller. Off-line dose reconstruction and evaluation show
      <0.5% dosimetric discrepancy from planned dose distribution for the test FM.
      CONCLUSION: This QA system is capable of identifying MLC position/fluence errors
      in near real-time, and assessing dosimetric impact of the treatment delivery
      process. It is thus a valuable tool for clinical implementation of online
      adaptive radiation therapy. (Research partially supported by Varian) Research
      partially supported by Varian Medical Systems.

PMID- 28518230
TI  - MO-F-213AB-01: Improving Dose Uniformity in Patch-Field Proton Therapy Using Beam
      Current Modulation.
AB  - PURPOSE: To improve the dose homogeneity in patch-field proton therapy using beam
      current modulation. METHODS: MCNPX simulations were performed for various
      configurations of the Mevion S250 beamline. Spread-out Bragg peak (SOBP) dose
      distributions were calculated, and lateral and distal dose profiles were
      extracted for through- and patch-field targets at depths ranging from 5.0 to 27.5
      cm. We define 'dose non-uniformity' (DNU) as the difference between the maximum
      and minimum dose relative to the prescription observed in a patched dose
      distribution. DNU was first calculated for dose distributions combining through
      field lateral dose profiles and with patch-field distal dose profiles, assuming a
      'standard' delivery with constant beam current. Distal dose profiles were then
      optimized using beam current modulation to better complement the lateral dose
      profiles when combined into a patched dose distribution. The DNU for optimized
      dose distributions was then calculated and compared to the DNU found for standard
      delivery. RESULTS: Using standard deliveries, DNU was 10% or less when patching
      lateral profiles 12.5-17.5 cm deep. Significantly greater DNU was observed for
      patches outside of this range, sometimes exceeding 35%. Using optimized distal
      profiles, DNU was reduced to 10% or less for all lateral profiles deeper than
      12.5 cm. Patches with lateral profiles shallower than 12.5 cm were not improved,
      as distal dose dropoff could not be improved to better match the sharp lateral
      dose dropoff. CONCLUSIONS: Optimizing beam current modulation can create distal
      profiles with more gradual dose falloff than found in a standard delivery,
      allowing optimized distal dose distributions to sum more homogeneously with
      lateral dose distributions. Thus, the hot or cold spots that often appear in
      patched dose distributions from standard deliveries can be mitigated by
      optimizing beam current. This method may also be applied to feathering methods or
      scanned beam deliveries to further improve patch-field dose homogeneity.
      Partially supported by MEVION Medical Systems, Inc.

PMID- 28518231
TI  - MO-A-218-01: CT Protocol Review - Practical Tips for Imaging Physicists.
AB  - In the 1980's and 90's, when every mammography department had a wet film
      processor and a sundial to keep the schedule, medical physicists performing
      mammography surveys were primarily focused on measuring machine performance and
      image quality. As our professional experience matured, medical physicists began
      to learn that they were uniquely qualified to help to recommend technique factors
      that would balance dose and image quality. Technique charts using different kVp,
      target-filter combinations and AEC modes gradually became common and patients
      benefitted from our input. With the revolutionary change in CT Scanner technology
      and utilization, medical physicists have begun to contribute their expertise to
      developing and improving CT protocols. This presentation will present practical
      challenges and offer some directions for the practicing medical physicist who
      desires to participate in this critical and emerging aspect of imaging physics
      practice: CT Protocol Review.

PMID- 28518232
TI  - MO-F-BRB-04: Fast Estimation of Secondary Particle Therapy Dose Using a Modified
      Track Repeating Method.
AB  - PURPOSE: Charged particle beams are of great interest, because they can achieve
      highly conformal radiation dose distributions. Despite this, some scattered
      radiation is inevitably present outside of the target volumes, and is of concern
      because of risks such as radiogenic cancer. Accurately calculating the secondary
      dose in regions far from the target volume is very difficult due to extremely low
      particle fluence and the effect of heterogeneities on particle ranges, making
      calculations possible only with CPU-week long Monte Carlo runs. By using a
      modified track repeating method, we demonstrate fast and accurate estimation of
      secondary dose appropriate for clinical use. METHODS: Primary and secondary
      particle track databases (including protons, electrons, photons, neutrons, and
      positrons) were generated with the Geant4 Monte Carlo toolkit. Several new
      strategies were developed or employed to improve the performance of non- primary
      particle propagation, including: (1) processing the databases such that only
      primary tracks producing deep penetrating photons or neutrons were kept and
      particles falling below transport thresholds were discarded, (2) a search
      algorithm that can locate a sub-track for a given energy in constant time, (3)
      multiplying photon and neutron tracks during propagation and scoring using
      particle 'splitting1. RESULTS: Performance and accuracy were benchmarked against
      full Monte Carlo calculations (Geant4 and FLUKA). Filtering out tracks that did
      not produce deep penetrating photons or neutrons did not affect the accuracy of
      the secondary dose calculation. Preliminary performance analysis indicated 60-
      100X speed up over Fluka and 700-1000X speed up over Geant4 with well maintained
      accuracy. CONCLUSIONS: Estimation of secondary dose from particle therapy has so
      far been largely an academic exercise. This method for fast estimation of
      secondary dose brings patient / plan specific information within reach, allowing
      clinicians to make informed decisions on the potential long-term risks associated
      with specific dose delivery plans. Partial funding from NSF grant CBET-0853157.

PMID- 28518233
TI  - MO-D-BRB-02: The Radiological Physics Center's Quality Audit Program: Where Can
      We Improve?
AB  - PURPOSE: To analyze the findings of the Radiological Physics Center's (RPC) QA
      audits of institutions participating in NCI sponsored clinical trials. METHODS:
      The RPC has developed an extensive Quality Assurance (QA) program over the past
      44 years. This program includes on-site dosimetry reviews where measurements on
      therapy machines are made, records are reviewed and personnel are interviewed.
      The program's remote audit tools include mailed dosimeters (OSLD/TLD) to verify
      output calibration, comparison of dosimetry data with RPC 'standard' data,
      evaluation of benchmark and patient calculations to verify the treatment planning
      algorithms, review of institution's QA procedures and records, and use of
      anthropomorphic phantoms to verify tumor dose delivery. The RPC endeavors to
      assist institutions in finding the origins of any detected discrepancies, and to
      resolve them. RESULTS: Ninety percent of institutions receiving dosimetry
      recommendations has remained level for the past 5 years. The most frequent
      recommendations were for not performing TG-40 QA tests, wedge factors, small
      field size output factors and off-axis factors. Since TG-51 was published, the
      number of beam calibrations audited during visits with ion chambers, that met the
      RPC's +/-3% criterion, decreased initially but has risen to pre-TG-51 levels. The
      OSLD/TLD program shows that only ~3% of the beams are outside our +/-5% criteria,
      but these discrepancies are distributed over 12-20% of the institutions. The
      percent of institutions with i,3 l beam outside the RPC's criteria is
      approximately the same whether OSLD/TLD or ion chambers were used. The first time
      passing rate for the anthropomorphic phantoms is increasing with time. The
      prostate phantom has the highest pass rate while the spine phantom has the
      lowest. CONCLUSIONS: Numerous dosimetry errors continue to be discovered by the
      RPC's QA program and the RPC continues to play an important role in helping
      institutions resolve these errors. This work was supported by PHS grants CA10953
      and CA081647 awarded by NCI.

PMID- 28518234
TI  - MO-D-213CD-01: Cartesian Methods for Rapid Time-Resolved MR Angiography.
AB  - : The physics of the MR image formation fundamentally trades off spatial
      resolution with temporal resolution. Time spent in acquiring data for the second
      image of a time series can alternatively be spent in sampling higher spatial
      frequencies for the first image to improve its spatial resolution. Historically
      this tradeoff has been addressed by making the k-space sampling rate high, such
      as with very short repetition times, and with methods such as view sharing in
      which only a portion of k-space is updated from one image to the next in a time
      series. Over a decade ago the method of parallel acquisition was proposed in
      which the signals detected by the individual elements comprising a multi-element
      receiver coil are used to provide further spatial discrimination and reduce
      acquisition time. These approaches include those based in image space (SENSE) or
      in k- space (SMASH, GRAPPA). In the last decade these methods have been
      integrated in contrast-enhanced MRA (CE-MRA) to provide a radical improvement in
      performance. CE-MRA is an application particularly well suited to these methods.
      The general desire for MRA images to be three-dimensional allows the use of 2D
      implementation of parallel acquisition, generally much more robust than 1D
      implementation. Also, the SNR loss associated with parallel acquisition is
      tempered in CE-MRA because high, arterial-phase signal is sampled throughout the
      data acquisition. Cartesian MR data acquisition, performed along a rectilinear
      sampling pattern in k-space, offers specific advantages in relative ease of
      implementation of 2D parallel acquisition and in "freezing" the status of the
      time-varying object at a specific timepoint by use of centric view ordering. This
      presentation will provide a review of these methods and how they have been
      effectively developed and integrated within the last decade for improved time
      resolved MRA. Cartesian k-space sampling patterns can now be quickly selected on
      a patient- and anatomy-specific basis for optimum acceleration. Receiver coil
      arrays have been adapted to allow up to 20* reduction in the number of k-space
      points sampled for a given spatial resolution. Reconstruction hardware now allows
      generation of 3D images within only hundreds of msec after data acquisition,
      permitting real-time generation of diagnostic quality images and their use in
      interactively guiding other processes. LEARNING OBJECTIVES: 1. Understand
      recently developed physics techniques which have allowed a 20x improvement in the
      speed of data acquisition for MR angiography 2. Understand how Cartesian sampling
      of k-space facilitates the practical and effective implementation of these
      techniques 3. Show how contemporary implementation of these physics techniques
      has provided a significant improvement in MRA image quality over the last decade.

PMID- 28518235
TI  - MO-C-BRCD-02: Physics of Cancer Cell Migration.
AB  - Two-dimensional (2D) in vitro culture systems have for a number of years provided
      a controlled and versatile environment for the study of cell adhesion and
      migration, two interrelated cell functions critical to cancer metastasis.
      However, the organization and functions of focal adhesion proteins in cells
      embedded in physiologically more relevant 3D matrices is qualitatively and
      functionally different from their organization and functions on conventional 2D
      planar substrates. In a 3D, crosslinked, fibrillar collagen matrix, cell
      migration and protrusion activity are still regulated by focal adhesion proteins,
      such as pl30Cas, FAK, Zyxin, Vinculin, Talin, and VASP, but differently from the
      2D case. This talk will describe the implications of the dependence of focal
      adhesion rotein-based cellular functions on microenvironmental dimensionality in
      cancer. We will discuss the implications of this work in cancer metastasis.

PMID- 28518236
TI  - MO-D-BRB-06: JUNIOR INVESTIGATOR WINNER - Fast and Accurate Patient Specific
      Collision Detection for Radiation Therapy.
AB  - PURPOSE: To develop a fast and generalizable method which can identify all
      possible hardware collisions specific to a given patient setup before treatment
      planning. METHODS: An anthropomorphic phantom placed in a typical breast setup
      using a wingboard was simulated on a CT scanner and the phantom body contour,
      table, and gantry geometry were made into polygon meshes using 3D modeling
      software. In the treatment room, a limited physical search of the collision
      positive zones was performed using the positioned phantom. A software tool that
      incorporated a generalized hierarchical bounding box (HBB) collision detection
      algorithm was developed and used to virtually map out the entire collision space
      by transforming the positions of the polygonal geometry over a given parameter
      range. RESULTS: The geometry containing 47K polygons was mapped over a space of
      6480 states with an average transform/collision check of 5.5ms, for a total time
      of 35.6s on a 3.14GHz dual core computer with 4GB memory. The computed collision
      space, using receiver operating curve analysis had an accuracy of 96.35%, and a
      positive predictive value of 91.2%. CONCLUSIONS: This work demonstrates a
      framework that can provide a fast and accurate map of the collision free space
      specific to any patient setup. Differences in physical and simulated collision
      space is attributed to inaccuracies of the geometrical models used. Future work
      includes improving the efficiency of the algorithm, enhancing the geometrical
      models and increasing the dimensions of the search.

PMID- 28518237
TI  - MO-D-217A-01: Optimizing Dose in the Interventional Suite: Do You Really Need
      That Image Quality?
AB  - : The imaging equipment used to guide interventions has evolved significantly in
      the recent past. As a result, the equipment has become more complex to operate.
      This evolution has left many operators ill equipped to fully optimize the
      radiation dose delivered, as they are often more focused on the technical skills
      required to complete the case rather than balancing image quality and radiation
      dose. In addition, they are usually better trained in these technical skills than
      in the delivery of optimal dose. Interventionalists are faced with dose
      optimization in two main venues: the angiography suite and the CT suite. In the
      angiographic suite, the operator has the ability to manipulate very simple
      parameters which can optimize dose. These, in combination with geometric and
      protective barrier techniques, can create a safe and efficient environment for
      patients, staff and operators. In addition, with the assistance of a medical
      physicist, operators can become more facile with their equipment and help to
      develop local protocols for their institution. In the CT suite, a similar
      approach can be applied. While the operator is more dependent on the technologist
      to manipulate the parameters during a case, the two can work together to optimize
      the dose for CT-guided procedures. Knowledge of the key variable parameters is
      paramount to developing this team approach. This course will review simple
      techniques that operators can employ to optimize dose during both
      fluoroscopically- and CT- guided procedures, and will examine the question, "Do
      you really need that image quality?" LEARNING OBJECTIVES: 1. Gain a better
      appreciation of the clinical perspective and need for operator education. 2.
      Identify simple techniques which can be employed to optimize dose with both
      fluoroscopically- and CT-guided interventions. 3. Discuss the importance of the
      question, "Do you really need that image quality?"

PMID- 28518238
TI  - MO-A-213CD-01: CT QC Testing Under the Draft ACR QC Manual.
AB  - : There are many recommendations for appropriate quality control for computed
      tomography scanners. The breadth of the recommendations is large and this has led
      to confusion as to what quality control is indeed necessary. The American College
      of Radiology is producing a QC Manual for CT under the auspices of the CT
      Accreditation Program. The draft manual is currently under final stages of
      review. LEARNING OBJECTIVES: 1. Review current recommendations for CT quality
      control 2. Describe the draft QC program of the ACR CT QC Manual 3. Discuss the
      status of the ACR CT QC Manual.

PMID- 28518239
TI  - MO-D-218-03: ACR Ultrasound Practice Accreditation and Technical Standard for
      Ultrasound Performance Monitoring.
AB  - : The first part of this presentation will provide an overview of the American
      College of Radiology (ACR) Technical Standard for Diagnostic Medical Physics
      Performance Monitoring of Real Time Ultrasound Equipment, as well as the ACR
      Accreditation requirements for general and breast ultrasound practices. The
      second part of the will discuss practical aspects of implementing QC programs
      that satisfy the requirements of the ACR practice accreditation programs,
      including consideration of personnel roles, and performance testing schedules,
      specific methods, and available tools. LEARNING OBJECTIVES: 1. Understand the ACR
      Technical Standard for Diagnostic Medical Physics Performance Monitoring of Real
      Time Ultrasound Equipment, and the QC requirements of the ACR Ultrasound and
      Breast Ultrasound Practice Accreditation Programs 2. Be able to implement
      ultrasound QC programs in keeping with these documents.

PMID- 28518241
TI  - MO-F-BRA-04: Voxel-Based Statistical Analysis of Deformable Image Registration
      Error via a Finite Element Method.
AB  - Purpose Clinical implementation of adaptive treatment planning is limited by the
      lack of quantitative tools to assess deformable image registration errors (R
      ERR). The purpose of this study was to develop a method, using finite element
      modeling (FEM), to estimate registration errors based on mechanical changes
      resulting from them. Methods An experimental platform to quantify the correlation
      between registration errors and their mechanical consequences was developed as
      follows: diaphragm deformation was simulated on the CT images in patients with
      lung cancer using a finite element method (FEM). The simulated displacement
      vector fields (F-DVF) were used to warp each CT image to generate a FEM image. B
      Spline based (Elastix) registrations were performed from reference to FEM images
      to generate a registration DVF (R-DVF). The F- DVF was subtracted from R-DVF. The
      magnitude of the difference vector was defined as the registration error, which
      is a consequence of mechanically unbalanced energy (UE), computed using 'in-house
      developed' FEM software. A nonlinear regression model was used based on imaging
      voxel data and the analysis considered clustered voxel data within images.
      Results A regression model analysis showed that UE was significantly correlated
      with registration error, DVF and the product of registration error and DVF
      respectively with R2=0.73 (R=0.854). The association was verified independently
      using 40 tracked landmarks. A linear function between the means of UE values and
      R- DVF*R-ERR has been established. The mean registration error (N=8) was 0.9 mm.
      85.4% of voxels fit this model within one standard deviation. Conclusions An
      encouraging relationship between UE and registration error has been found. These
      experimental results suggest the feasibility of UE as a valuable tool for
      evaluating registration errors, thus supporting 4D and adaptive radiotherapy. The
      research was supported by NIH/NCI R01CA140341.

PMID- 28518240
TI  - MO-F-BRCD-01: Stereotactic Body Radiation Therapy: Updates on Clinical,
      Biological, and Physics/QA:SBRT (Part 1): Biological and Clinical Updates.
AB  - Stereotactic Body Radiation Therapy (SBRT) is an important form of cancer therapy
      with increasingly broad application across a spectrum of tumor types in primary
      and metastatic settings. In this presentation the radiation biology, clinical
      experience from various trials, and cautionary updates on normal tissue
      tolerances will be presented. The effective radiobiology of SBRT and
      hypofractionated courses of therapy has become more evident with the increasing
      reports of retrospective clinical outcomes and prospective clinical trial
      results. Current open multi-institutional national cooperative trials will be
      reviewed. Accumulating clinical experiences are yielding new insights into
      practical aspects of tumor and normal tissue responses to high dose per fraction
      treatment. Indeed, SBRT has produced profound tumoricidal and ablative effects,
      however there is potential for grave toxicity and this demands that clinicians be
      knowledgeable regarding normal tissue tolerances for various hypofractionated
      courses. As a final note, the technology associated with SBRT has evolved
      remarkably in the last decade, and procedures that originally required hours to
      plan, with cumbersome quality assurance methods, arduous set-up times, and long
      protracted deliveries can now be performed in ever shorter time periods. Given
      these technology improvements and recognizing the great palliative potential of
      hypofractionated radiation therapy to relieve cancer symptoms quickly and
      efficiently, a new strategy to deliver SBRT in a single session called STAT RAD
      is presented for discussion.

PMID- 28518242
TI  - MO-F-211-01: Methods for Completing Practice Quality Improvement (PQI).
AB  - : Practice Quality Improvement (PQI) is becoming an expected part of routine
      practice in healthcare as an approach to provide more efficient, effective and
      high quality care. Additionally, as part of the ABR's Maintenance of
      Certification (MOC) pathway, medical physicists are now expected to complete a
      PQI project. This session will describe the history behind and benefits of the
      ABR's MOC program, provide details of quality improvement methods and how to
      successfully complete a PQI project. PQI methods include various commonly used
      engineering and management tools. The Plan-Do-Study-Act (PDSA) cycle will be
      presented as one project planning and implementation tool. Other PQI analysis
      instruments such as flowcharts, Pareto charts, process control charts and
      fishbone diagrams will also be explained with examples. Cause analysis, solution
      development and implementation, and post-implementation measurement will be
      presented. Project identification and definition as well as appropriate
      measurement tool selection will be offered. Methods to choose key quality metrics
      (key quality indicators) will also be addressed. Several sample PQI projects and
      templates available through the AAPM and other organizations will be described.
      At least three examples of completed PQI projects will be shared. LEARNING
      OBJECTIVES: 1. Identify and define a PQI project 2. Identify and select
      measurement methods/techniques for use with the PQI project 3. Describe
      example(s) of completed projects.

PMID- 28518243
TI  - MO-A-217A-02: Prostate and Pelvic Lymph Node Anatomy for Contouring.
AB  - : Three-dimensional image guided radiotherapy requires familiarity with axial
      anatomy of human body to facilitate accurate contouring of target volume for
      radiotherapy treatment planning. In this session we will review the axial anatomy
      of male pelvis using images from the visible human project. There will be a
      review of the literature on how the contour guidelines were formulated and their
      clinical application on a CT image set. LEARNING OBJECTIVES: 1. Know the common
      anatomical landmarks in pelvis used for contouring. 2. Know the contouring
      guidelines used in published contouring atlas. 3. Know how to use the contouring
      guidelines in the clinic.

PMID- 28518244
TI  - MO-F-BRB-03: A Method to Assess the Need for Clinical Monte Carlo Dose
      Calculations for Small Proton Therapy Fields.
AB  - PURPOSE: Due to multiple Coulomb scattering in complex geometries, small field
      dosimetry in proton therapy is challenging. Our goal was to define an indicator
      for the accuracy of dose delivery based on analytical dose calculations in
      treatment planning systems for small (e.g. radiosurgery) proton therapy fields.
      METHODS: Seven patients whose treatment involved one or more small fields (below
      ~3.6cm in diameter) were selected. We developed a fast methodology to quantify
      the inhomogeneity of the tissue traversed by a single beam using a heterogeneity
      index (HI). The implementation was based on the dose calculation approach taken
      by our pencil beam algorithm. Plans created with the treatment planning system
      were verified against Monte Carlo dose calculations on a field- by-field basis.
      DVHs were analyzed and differences in the dose to the GTV were assessed. The
      correlation between the HI-values and the discrepancies between planning system
      and Monte Carlo in terms of absolute dose to the target was studied. RESULTS: Our
      treatment planning system overestimates the dose within the GTV for very small
      fields by up to ~8%, even if proper output factor normalization is done in water.
      The differences are strongly correlated to HI (Spearman's rho=0.8, rho<0.0001).
      More complex heterogeneities within the beam path caused larger errors by the
      analytical algorithm. With the established correlation a threshold for the HI can
      be set by choosing a tolerance level. CONCLUSIONS: The HI as defined in this
      study appears to be a good indicator of the accuracy of proton field delivery in
      terms of GTV prescription dose when small fields are being delivered. Each HI
      value was obtained in less than 2 minutes allowing implementation of the HI
      algorithm in clinical routine. For HI- values exceeding a certain threshold,
      either a change in beam incidence or a Monte Carlo dose calculation should be
      considered.

PMID- 28518245
TI  - MO-D-BRB-01: Accuracy Requirements and Uncertainties in Radiation Therapy: A
      Preview of an Upcoming IAEA Report.
AB  - PURPOSE: The International Atomic Energy Agency (IAEA) has a mandate 'to
      accelerate and enlarge the contribution of atomic energy to peace, health and
      prosperity throughout the world'. Through its Human Health Division, this is done
      by developing guidance documents on standards of practice in radiation medicine.
      In recent years, there have been major advances in the technology of radiation
      oncology which have allowed for a transition from conventional 2-D radiation
      therapy to the implementation of 3-D conformal radiation therapy (CRT), intensity
      modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT),
      adaptive radiation therapy (ART), and 4-D imaging and motion management in
      radiation therapy. Brachytherapy procedures have also evolved both for high dose
      rate (HDR) techniques as well as permanent implants, especially for prostate
      cancer treatments. Multiple imaging modalities are now available for target
      volume and normal tissue delineation for radiation treatment planning both for
      external beam radiation therapy and brachytherapy. With these new advanced
      technologies and improved outcome considerations for both external beam and
      brachytherapy, there is also a recognized need for greater accuracy in the
      radiation treatment process. METHODS: While a number of reports and publications
      have defined accuracy needs in radiation oncology, most of these reports were
      developed in an era with different radiation technologies and date back to the
      1980s and 90s. RESULTS: In view of the new technologies and techniques,
      improvements in dosimetry methodologies and new clinical dose- volume data, the
      IAEA is developing a new international guidance document on 'Accuracy
      Requirements and Uncertainties in Radiation Therapy' in order to reduce these
      uncertainties to provide more effective and safer patient treatments.
      CONCLUSIONS: This review will summarize the new IAEA report which is expected to
      be published later in 2012. This work is supported by the International Atomic
      Energy Agency.

PMID- 28518246
TI  - MO-D-BRA-01: Limits of Dose Reduction in CT: Where are They and How Will We Know
      When We Get There?
AB  - : Radiation Dose continues to be a concern with respect to all diagnostic imaging
      using ionizing radiation, but especially so with CT imaging. We have always known
      how to reduce radiation dose in CT - for example, simply turning down the system
      output (e.g. reduce mAs). What we have not been able to do is to simultaneously
      reduce dose and maintain "diagnostic image quality". Many recent technical
      developments have appeared, and will continue to appear, that will allow users to
      reduce radiation dose in CT while "maintaining image quality". However, this last
      term is ill-defined and current metrics of image quality are not very applicable
      to actual clinical practice. The purpose of this symposium is to: (a) describe
      several current and possible future radiation dose reduction methods and the
      magnitude of their potential for dose reduction, (b) some description of what
      "diagnostic image quality" means, the effects that dose reductions methods have
      on this property, description of some metrics that may help us assess this
      property quantitatively and this information can be used to guide how low
      radiation doses can be reduced. LEARNING OBJECTIVES: 1. Understand both
      conventional and emerging radiation dose reduction methods in CT. 2. Understand
      the implications on diagnostic image quality for each radiation dose reduction
      method. 3. Understand some of the issues in evaluating how much radiation dose
      can be reduced and still accomplish a diagnostic imaging task.

PMID- 28518248
TI  - MO-C-BRCD-01: Towards Personalized Medicine: Integration of Imaging into Therapy.
AB  - : A significant advance in cancer therapy is currently underway with the
      evolution from a population-based to a personalized patient-based prescription.
      Rapid developments in imaging, particularly adoption of molecular imaging, offer
      unprecedented opportunities for accurate characterization of tumor biology, as
      well as early assessment of treatment response. Accurate characterization of
      tumor biology enables effective selection of appropriate therapy or even a design
      of purposefully non-uniform tumor-specific treatment plans, tailored to the
      spatial distribution of biological properties of each patient's tumor. Early
      assessment of treatment response enables treatment adaptation, potentially
      intensifying or reducing the treatment dose to provide more efficacious and less
      toxic therapies. However, integration of imaging into therapeutic applications
      requires a high level of image quantification, well beyond what is currently
      required in diagnostic imaging applications. This lecture will provide an
      overview of imaging applications in therapy, ranging from target selection
      totreatment response assessment. Potential roadblocks, as well as research
      opportunities on the path to personalization of cancer therapy, will be
      highlighted. LEARNING OBJECTIVES: 1. Understand the role of imaging in target
      definition and treatment response assessment 2. Understand the requirements for
      establishing imaging as a biomarker 3. Learn about research opportunities on the
      interface between imaging and therapy.

PMID- 28518247
TI  - MO-F-213AB-04: Biological Effect of Dose Shadowing by Fiducial Markers in Spot
      Scanning Proton Therapy with a Limited Number of Fields.
AB  - PURPOSE: In spot scanning proton therapy, accurate patient positioning before and
      during treatment is essential. A small gold ball marker is suitable as a fiducial
      for prostate treatment. However, it has been pointed out that the marker causes
      dose shadowing because the protons are scattered with their energy quickly
      diminished. In this research we explore the possibility that the biological
      effect of dose shadowing can be mitigated with a limited number of fields.
      METHODS: The proton dose distribution in prostate was simulated using Geant4. The
      simulations include the Hokkaido University spot scanning nozzle and a water
      phantom positioned isocentrically. The PTV was delineated at the center of the
      phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV.
      The plan was created by single-field optimization and each of the following beam
      arrangements was investigated; (1) single lateral field (2) two lateral fields
      (3) two lateral + one anterior fields (4) four-field box. The dose prescription
      was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP)
      were compared for the four beam arrangements. RESULTS: For (1)-(4), the minimum
      dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The
      reduction of the TCP values from those in the absence of the gold marker were
      50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al.
      (Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the
      biological parameters in LevegrA1/4n et al. (Int.J.RadiatOncol.Biol.Phys. 51,
      2001), respectively. CONCLUSIONS: Although dose shadowing by the gold marker is
      locally non-negligible, the size of the affected domain is tiny. It was found
      that with a minimum number of fields, the TCP nearly recovers to the value
      without the gold marker.

PMID- 28518249
TI  - MO-D-BRB-05: An Analysis of 13,000 Patient-Specific IMRT QA Results from 13
      Different Clinical Treatment Services.
AB  - PURPOSE: To review an institution's patient-specific IMRT quality assurance (QA)
      results, including absolute dose and gamma analysis measurements. METHODS:
      Patient-specific IMRT QA records were reviewed to obtain information on absolute
      dose difference (ion chamber measurement; +/-3% agreement criteria) and
      percentage of pixels passing gamma (film measurement; 5%/3 mm agreement criteria)
      from 2005 to 2011. The 13,002 plans reviewed, were classified by treatment
      service: breast (n=67), central nervous system (n =1383), gastrointestinal
      (n=803), genitourinary (n=1831), gynecology (n=935), hematology (n=380), head and
      neck (n=3697), intensity-modulated stereotactic spine radiation therapy (n=341),
      melanoma (n=54), mesothelioma (n=52), pediatric (n=307), sarcoma (n=201), and
      thoracic (n=2951). All records were analyzed for trends according to measurement
      date and treatment service. Plans failing to meet QA criteria were further
      evaluated for subsequent measured data. RESULTS: Mean difference (+/- one
      standard deviation) between the measured and calculated doses was -0.29% +/-
      1.64% (with the calculated values being slightly higher). The mean percentage of
      pixels passing gamma was 97.7% (lower 95th percentile, 92.2%). The plan pass
      rates were 97.7% and 99.3% for absolute dose and gamma, respectively. We observed
      statistically significant differences (p < 0.05) in both absolute dose and gamma
      measurements as a function of treatment service (particularly for stereotactic
      spine and mesothelioma services) and measurement date (average agreement improved
      with time). However, despite improved agreement between measured and calculated
      doses, the percentage of treatment plans failing to meet the passing criteria has
      remained largely constant at ~2.3%. CONCLUSIONS: Our retrospective review of
      13,002 patient-specific IMRT QA plans demonstrated that plans continue to fail
      IMRT QA criteria at a consistent rate. This rate serves as a clinical reference
      for expected rates of QA plan pass and failure for a variety of treatment
      services.

PMID- 28518250
TI  - MO-D-213CD-04: 4D X-Ray DSA and 4D Fluoroscopy.
AB  - : During the past decade the use of undersampled acquisition and constrained
      reconstruction have led to significant increases in data acquisition speed, SNR,
      spatial resolution and temporal resolution in MR imaging. When a separately
      acquired constraining image is combined with an angiographic time series the
      traditional tradeoff between spatial and temporal resolution is greatly reduced.
      Artifacts and limited resolution that would normally be associated with a rapid
      highly undersampled temporal image series are mitigated by the constrained
      reconstruction process which transfers the SNR and spatial resolution of the
      constraining image to the individual time frames. In rotational C-Arm DSA a 3D
      image volume is formed from all the projections acquired during the C-Arm
      rotation. Although the individual projections contain temporal information, the
      reconstructed 3D image has no temporal information and represents a composite of
      the vascular filling that has occurred during the iodine injection. However, the
      3D cone beam CT reconstruction can be used to constrain the reconstruction of one
      3D volume for each of the rotational projections. This extends the traditional
      DSA time series of 2D images to a series of 3D volumes at rates up to 30 per
      second. Similar techniques can be used to provide fluoroscopy that can be
      embedded in the 3D space of the constraining volume and viewed from arbitrary
      angles without gantry motion. This overcomes the problem of forbidden views and
      guarantees that an intervention can be done without having to send patients to
      surgery. Unlike 4D DSA which requires only one source and receptor, 4D
      Fluoroscopy requires a bi-plane fluoroscopy system. LEARNING OBJECTIVES: 1. To
      understand the application of under sampling and constrained reconstruction to 4D
      DSA and Fluoroscopy.

PMID- 28518251
TI  - MO-A-BRA-01: State of the Art in Quantitative Imaging in CT, PET and MRI.
AB  - : Diagnostic Imaging is evolving from a modality where the emphasis is on the
      acquisition and interpretation of image data by radiologists to one where imaging
      devices may be used as measurement devices that are able to produce quantitative
      results. Some examples of quantitative measured values are already in clinical
      practice, including coronary artery calcium scores from CT, Standard Uptake
      Values (SUV) in PET imaging and Diffusion Weighted Imaging (DWI) in MRI. Clinical
      and clinical research applications of quantitative anatomical and functional
      imaging biomarkers, including those focused on treatment assessment, have
      continued to dramatically expand. Studies at single centers have clearly
      demonstrated the potential of such applications. However, sources of bias and
      variance of quantitative imaging biomarkers have not previously been adequately
      investigated, thus limiting the implementation of robust methods to mitigate
      their effects. Therefore, when it comes to applications of such techniques across
      vendor platforms, centers, and time, challenges arise due to lack of standards,
      appropriate phantoms, and protocols. During the past few years, several
      quantitative imaging initiatives have been instigated. This symposium
      presentation will review selected applications of quantitative imaging
      biomarkers, illustrate some of the current challenges in broadening the use of
      such biomarkers, and discuss some of the current initiatives of various
      scientific and federal organizations that are focused on the standardization,
      qualification, and validation of quantitative imaging biomarkers. LEARNING
      OBJECTIVES: 1. Understand selected applications of quantitative imaging
      biomarkers. 2. Understand the factors that currently limit widespread acceptance
      and use of such quantitative imaging biomarkers, including sources of bias and
      variance. 3. Understand some of the current initiatives focused on the
      standardization, qualification, and validation of selected quantitative imaging
      biomarkers. LEARNING OBJECTIVES: 1. Understand selected applications of
      quantitative imaging biomarkers. 2. Understand the factors that currently limit
      widespread acceptance and use of such quantitative imaging biomarkers, including
      sources of bias and variance. 3. Understand some of the current initiatives
      focused on the standardization, qualification, and validation of selected
      quantitative imaging biomarkers.

PMID- 28518252
TI  - MO-D-211-01: Medical Physics Practice Guidelines - The Minimum Level of Medical
      Physics Support in Clinical Practice Settings.
AB  - : The American Association of Physicists in Medicine (AAPM) has long advocated a
      consistent level of medical physics practice, and has published many guidelines
      and position statements toward that goal, such as Science Council Task Group
      reports related to calibration and quality assurance, Education Council and
      Professional Council Task Group reports related to education, training, and peer
      review, and Board-approved Position Statements related to the Scope of Practice,
      physicist qualifications, and other aspects of medical physicspractice. Despite
      these concerted and enduring efforts, the profession does not have a clear and
      concise statement of the acceptable practice guidelines for routine clinical
      medical physics. As accreditation of clinical practices becomes more common,
      Medical Physics Practice Guidelines (MPPGs) will be crucial to ensuring a
      consistent benchmark for accreditation programs. The AAPM will lead the
      development of MPPGs in collaboration with other professional societies. The
      MPPGs will be freely available to the general public. Accrediting organizations,
      regulatory agencies and legislators will be encouraged to reference these MPPGs
      when defining their respective requirements. MPPGs are intended to provide the
      medical community with a clear description of the minimum level of medical
      physics support that the AAPM would consider to be prudent in all clinical
      practice settings. Support includes but is not limited to staffing, equipment,
      machine access, and training. These MPPGs are not designed to replace extensive
      Task Group reports or review articles, but rather to describe the recommended
      minimum level of medical physics support for specific clinical services. This
      course will describe the purpose and scope of MPPGs, the procedure for the
      development of a MPPG, as well as the progress of Therapy MPPG TG #1 on
      "Evaluation and quality assurance of x-ray based image guided radiotherapy
      systems" and Diagnostic MPPG TG #2 on "CT Protocol management and review".
      LEARNING OBJECTIVES: 1. Understand the concept and scope of MPPG from the AAPM 2.
      Understand the benefits and process of the development of MPPG by the AAPM 3.
      Understand the goals and methodology of the Therapy MPPG Task Group #14. 4.
      Understand the strategic plans from Professional Council towards the AAPM
      initiatives.

PMID- 28518253
TI  - MO-D-218-02: Ultrasound Phantoms in Image Quality Measurements and Performance
      Assessment.
AB  - Agreement has recently emerged for measurement of only three parameters in
      routine quality assurance. These include element or channel failure (EOCF),
      maximum depth of penetration (MDOP) and distance measurement accuracy (DMA). The
      related study leading to this agreement was done at the Mayo Clinic ["Four-year
      experience with a clinical ultrasound quality control program," Hangiandreou et
      al. Ultrasound Med & Biol, vol. 37, pp. 1350-1357 (2011)]. A variety of phantoms
      have been proposed for performing these measurements. These include: 1) a phantom
      with both flat and cone-shaped scanning windows, tissue-mimicking material and
      parallel nylon fibers for measuring all three parameters; 2) a starch suspension
      in water phantom for assessing ECOF; 3) polyurethane phantom for determining ECOF
      and estimating MDOP; 4) a silicone phantom for determining ECOF. Determination of
      ECOF and MDOP requires acquisition of image cine loops including many
      statistically independent versions; analysis of the data requires averaging of
      the images in the cine loops, and software is being tested at the time of this
      writing for user-friendly downloading and averaging of the cine images. The
      phantoms will be described and examples of procedures and results for making
      measurements. One method for assessing imaging performance involves quantifying
      the detectability of small low-echo spheres as a function of depth; detectability
      will depend on sphere size and on depth. It can be argued that the smaller the
      sphere and the greater the detectability, the better the scanner can delineate
      the boundary of an inclusion such as a spiculated cancer. Phantoms and software
      will be described which allow quantitative determination of detectability of low
      echo spheres (&#61485; 40 dB) as a function of depth; one phantom has a spatially
      random distribution of 4-mm diameter low-echo spheres for lower frequencies, and
      the other 2-mm diameter spheres for higher frequencies. The parameter that is
      quantified is the mean lesion signal-to-noise ratio (LSNR) as described for
      cylinders by Lopez H et al. IEEE Trans Med Imaging, 1992 and for spheres by
      Kofler et al. Ultrasound Med & Biol, 2005. The phantoms accommodate any size and
      shape transducer. Note that spheres have no preferred orientation; therefore,
      phased arrays and convex (curved) arrays with a broad range of radii of curvature
      and sector angles can be can be assessed. Phantoms for assessing other aspects of
      performance such as quantitative determination of the contrast of large objects
      in a background will also be discussed.

PMID- 28518254
TI  - MO-F-213AB-06: Experimental Evaluation of Radiation Dose Effect by High Atomic
      Number Materials for Superficial Radiation Therapy.
AB  - PURPOSE: High atomic number (Z) materials have been considered as a method for
      enhancing radiation dose in tumors. The dose enhancement due to interactions of
      kilovoltage x-rays with high-Z materials (i.e., gold or iodine) has been well
      demonstrated through computational works. This study is to experimentally
      quantify the effect using gold nanoparticles (AuNPs) and iodine solutions,
      respectively. METHOD AND MATERIALS: Iodine and AuNPs (AuroVist, Nanoprobes,
      Yaphank NY) are uniformly distributed in each cylinder phantom (1.6 cm diameter
      and 2.0 cm depth) separately. Concentrations of Iodine and AuNPs were varied from
      40 to 225 mg/ml and 16.0 mg/ml to 42.7 mg/ml, respectively. The Iodine solutions
      were irradiated with 75 to 150 kVp x-rays from a superficial x-ray therapy
      machine at doses of 250 to 400 cGy. The AuNPs solutions in the cylinder were
      irradiated with 40 to 150 kVp x-rays. The phantom was placed at the center of the
      cone to ensure a uniform radiation field. Radiation doses were measured using
      GafChromic EBT2 films (International Specialty Products, Wayne NJ). Dose
      enhancement factors (DEF), i.e., the ratio of dose to high-Z material versus dose
      to water, were calculated and plotted as functions of concentration and kVp.
      RESULTS: Experimental DEFs varied between 1.01 and 1.38. The DEFs increased with
      increasing concentration and varied with changing kVp. The maximum DEF measured
      for Iodine solution was 1.38 at 225 mg/ml and 150 kVp. The maximum DEF measured
      for AuNPs was 1.22 at 42.7 mg/ml and 40 kVp. The target volume covered by dose
      enhancement is larger with relatively lower concentrations. CONCLUSIONS: The
      magnitude of dose enhancement due to AuNPs and Iodine presence has a dependency
      with the concentration and kVp. In clinical applications, the concentration of
      the high-Z material and kVp should also be selected to suit the depth and volume
      of the target tumor.

PMID- 28518256
TI  - MO-E-217A-01: Contrast-Enhanced Spectral Mammography - Physical Aspects and QA.
AB  - PURPOSE: To describe the current state of dual energy contrast-enhanced digital
      mammography, to discuss those aspects of its operation that require evaluation or
      monitoring and to propose elements of a program for quality assurance of such
      systems. METHODS: The principles of dual-energy contrast imaging will be
      discussed and tools and techniques for assessment of performance will be
      described. RESULTS: Many of the elements affecting image quality and dose
      performance in digital mammography (eg noise, system linearity, consistency of x
      ray output and detector performance, artifacts) remain important. In addition,
      the ability to register images can influence the resultant image quality. The
      maintenance of breast compression thickness during the imaging procedure and
      calibration of the system to allow quantification of iodine in the breast
      represent new challenges to quality assurance. CONCLUSION: CESM provides a means
      of acquiring new information regarding tumor angiogenesis and may reveal some
      cancers that will not be detectable on digital mammography. It may also better
      demonstrate the extent of disease. The medical physicist must understand the
      dependence of image quality on physical factors. Implementation of a relevant QA
      program will be required if the promise of this new modality is to be delivered.

PMID- 28518257
TI  - MO-A-217A-01: An Introduction to Contouring - Neck and Thorax.
AB  - : In the last decade IMRT and related treatment modes have become de facto, if
      not actual standards of care. These modes are heavily dependent on the anatomical
      modeling phase of treatment planning. It may in fact be argued that this is the
      most important step in the planning process, as the optimization and plan
      evaluation will be directly affected by a good or poor anatomical model.
      Physicists have increasingly been called upon to do much of this contouring, yet
      have traditionally had only a brief formal introduction to anatomy. This session
      will provide a brief overview and refresher on two anatomical regions that have
      come to be most often treated by IMRT and like modalities. Dr. Jonn Wu will
      discuss the contouring of prominent normal structures and target volumes in the
      thorax using multiple imaging modalities, and illuminate key concepts in
      identifying these structures. Emphasis will be placed on relevance to SBRT. Dr. I
      Chow Hsu will discuss the structures in the pelvis relevant to prostatic
      treatments, including pelvic lymphatic chains, using CT and the Visible Human
      Project. LEARNING OBJECTIVES: 1. To better understand how to identify structures
      in the thorax 2. To better understand how to identify structures in the pelvis
      relevant to prostate treatments 3. To understand the impact and pitfalls of
      different imaging modalities in these anatomical locations.

PMID- 28518258
TI  - MO-F-BRB-02: Macro Monte Carlo for Proton Dose Calculation in Different
      Materials.
AB  - PURPOSE: Although the Monte Carlo (MC) method allows accurate dose calculation
      its usage is limited due to long computing time. In order to gain efficiency, a
      new macro MC (MMC) technique for proton dose calculations in homogeneous
      materials has been developed. METHODS: The macro MC is based on a local to global
      MC approach. The local simulations using Geant4 consist of mono-energetic proton
      pencil beams (10 to 250 MeV) impinging perpendicularly on slabs of different
      thicknesses (1-10 mm) and different materials (water, lung, muscle, adipose,
      bone). During the local simulation multiple scattering, ionization, elastic and
      inelastic interactions have been taken into account and the physical
      characteristics such as lateral displacement and energy loss have been scored for
      primary and secondary particles. The scored data from appropriate slabs is then
      used for the stepwise transport of the protons in the MMC simulation while
      calculating the energy loss along the path between entrance and exit position.
      Additionally, ions and neutrons are taken into account for the dose calculation.
      In order to validate the MMC, calculated dose distributions using the MMC
      transport and Geant4 have been compared for different mono-energetic proton
      pencil beams impinging on phantoms with different homogeneous materials. RESULTS:
      The agreement of calculated integral depth dose curves is better than 1% or 1 mm
      for all pencil beams and materials considered. For the dose profiles the
      agreement is within 1% or 1 mm for all energies, depths and materials. The
      efficiency of MMC is about 200 times higher than for Geant4. CONCLUSIONS: The
      dose comparisons demonstrate that the new MMC results in very accurate and
      efficient dose calculations for proton beams in homogeneous materials. In future,
      the MMC method will be extended to inhomogeneous situations in order to allow
      patient dose calculations for proton beams. This work was supported by Varian
      Medical Systems.

PMID- 28518259
TI  - MO-D-BRCD-01: Overview of Clinical Dosimetry and Quality Assurance in Proton
      Therapy.
AB  - : An overview of current status of clinical proton dosimetry is presented.
      Absolute dosimetry in proton beams using IAEA TRS 398 and ICRU 59 dosimetry
      protocols is presented. An overview of the use of various detectors for proton
      therapy beam characterization is presented including Ion Chambers for point
      measurements, Multi-Layer Ionization Chambers (MLICs) for percentage depth dose
      (PDD) measurements, and other types of detectors such as TLDs and diodes. The use
      of ID and 2D commercial arrays for routine dosimetry for performing daily output,
      range verification, symmetry, and flatness is also presented. Some of the
      challenges in the design and performance of certain detectors related to LET
      quenching effects is discussed. The use of film (radiographic and radiochromic)
      for various beam QA tasks is discussed. Current status and prospects of 3D
      dosimetry for particle therapy is also presented. Specific challenges in quality
      assurance with certain beam delivery technologies are also discussed such as
      pencil beams, scattered beams, and uniform scanning beams. Proton machine QA
      checks such as daily, monthly, and annual QA, as well as patient specific proton
      beam QA are presented. LEARNING OBJECTIVES: 1. Understand proton beam dosimetry
      protocols 2. Familiarization with proton dosimetry tools and their limitation 3.
      Understand the challenges and procedures in proton therapy QA.

PMID- 28518260
TI  - MO-D-BRB-11: Out-Of-Field Dose Measurements in Radiotherapy Using Photons and
      Particles.
AB  - PURPOSE: Within the European project ALLEGRO (grant agreement no. 231965), the
      out-of-field dose delivered to a patient when treated with different radiotherapy
      modalities was investigated. The study compared the dose distribution during
      photon and particle irradiations both in a water and an anthropomorphic phantom
      to evaluate the risk of inducing secondary malignancies. METHODS: Two sets of
      experiments with standardized conditions were used for a systematic comparison.
      In the former, a water phantom was irradiated with a 2D squared field to
      characterize the lateral dose fall-off with high spatial resolution. The latter
      employed an anthropomorphic phantom treated for a target volume placed at the
      center of its head to simulate a brain tumor. The dose was measured in several
      planes along the phantom main axis. For both types of experiments the dose was
      measured with a PTW diamond detector. Additionally, the use of TLDs and bubble
      detectors provided some information on the secondary neutron field produced both
      in the accelerator structure and the target itself. In total, experiments were
      conducted at six facilities using photons, protons and carbon ions; the ion
      irradiations were performed with passive delivery and the scanning technique.
      RESULTS: A significant difference among the out-of-field dose profiles is
      observed for distances larger than 3 cm to the target. The distribution delivered
      by photons is a factor 10 to 400 higher than the values of charged particles.
      Scanning ions reduces the out-of-field dose more than passive delivery at
      distances larger than 10 cm. CONCLUSIONS: The study emphasizes the physical
      advantage of using charged particles for tumor therapy. Together with the
      favorable depth dose deposition, ions spare the normal tissue surrounding the
      target more efficiently than photons. These results imply a lower risk of long
      term effects, such as the induction of secondary malignancies, following
      treatments with particles compared to photons. This work was funded by the
      European ALLEGRO project (Grant Agreement No. 231965).

PMID- 28518261
TI  - MO-F-213AB-03: Potential Reduction in Out-Of-Field Dose in Pencil Beam Scanning
      Proton Therapy Through Use of a Patient-Specific Aperture.
AB  - PURPOSE: Patient specific apertures are commonly employed in passive double
      scattering (DS) proton therapy (PT). This study was aimed at identifying the
      potential benefits of using such an aperture in pencil beam scanning (PBS).
      METHODS: An accurate Geant4 Monte Carlo model of the PBS PT treatment head at
      Massachusetts General Hospital (MGH) was developed based on an existing model of
      the passive double-scattering (DS) system. The Monte Carlo code specifies the
      treatment head at MGH with sub-millimeter accuracy and was configured based on
      the results of experimental measurements performed at MGH. This model was then
      used to compare out-of-field doses in simulated DS treatments and PBS treatments.
      The PBS treatments were simulated both with and without the patient-specific
      aperture used in the DS treatment. RESULTS: For the conditions explored, a
      typical prostate field, the lateral penumbra in PBS is wider than in DS, leading
      to higher absorbed doses and equivalent doses adjacent to the primary field edge.
      For lateral distances greater than 10cm from the field edge, the doses in PBS
      appear to be lower than those observed for DS. Including an aperture at nozzle
      exit reduces the penumbral width by preventing wide-angle scatter from reaching
      the patient. This can reduce the dose in PBS for lateral distances of less than
      10cm from the field edge by over an order of magnitude and allow better dose
      conformity. CONCLUSIONS: Placing a patient-specific aperture at nozzle exit
      during PBS treatments can potentially reduce doses lateral to the primary
      radiation field by over an order of magnitude. This has the potential to further
      improve the normal tissue sparing capabilities of PBS. The magnitude of this
      effect depends on the beam spot size of the scanning system and is thus facility
      dependent.

PMID- 28518262
TI  - MO-B-218-01: Managing the Pediatric Patient's CT Dose: The Role of SSDE.
AB  - : As many as 6 - 8 million CT scans are performed annually in the United States
      on pediatric patients. The majority of these CT scans are not performed in
      pediatric hospitals that specialize in addressing the unique requirements of
      pediatric imaging. Instead, most of these scans occur in adult hospitals, where
      pediatric CT scanning is a small fraction of the total caseload. Both adult and
      pediatric hospitals need a simple method that allows the management of the CT
      radiation dose received by each patient based on the patient's physical size.
      This lecture suggests some simple tools and techniques that the qualified medical
      physicist can introduce to an individual practice in an effort to properly manage
      CT doses. This lecture begins by exploring the unique challenges presented by the
      pediatric patient in the management of their radiation dose during CT scanning.
      This is followed by an explanation of the basic science behind the development of
      the Size Specific Dose Estimate (SSDE) in CT, the strengths and weaknesses of the
      method, and some sample calculations. The presentation concludes by exploring the
      clinical application of SSDE in the day to day management of the radiation dose
      during CT scanning of not only small pediatric patients, but also patients who
      are larger than the average size adult. LEARNING OBJECTIVES: 1. Understand the
      basic challenges associated with CT imaging of children. 2. Understand the basic
      science used to develop SSDE, its strengths and its limitations 3. Understand the
      application of SSDE in the clinic in the daily management of pediatric CT doses.

PMID- 28518263
TI  - MO-F-BRB-06: Gold Nanoparticle Modify Density of Ionizations inside Cells
      Submitted to Radiation Therapy: Microscopic Track Analysis of Secondary Electrons
      Using Monte Carlo.
AB  - PURPOSE: Study density of ionization in cells containing gold nanoparticles
      (AuNP) submitted to Radiation Therapy. METHODS: Spherical gold nanoparticles with
      diameters ranging 0-100nm were considered evenly distributed inside a 20mgr;m
      cubic cell, maintaining the gold concentration of 0.01%, with constant number of
      gold atoms inside the cell. Monte Carlo simulations were performed using PENELOPE
      code considering event-by-event transport of secondary electrons with minimum
      energy of 1keV. Simulated clinical energy spectrum of 250kV and 6MV x-rays;Co-60
      and Ir-192 gamma-ray sources obtained at each corresponding build-up depths were
      considered. Density of ionization inside the cell was evaluated counting delta
      electrons created either in AuNP or cell, excluding electrons attenuated inside
      the nanoparticles. The dose enhancement resultant from interaction of electrons
      with few micrometers range was quantified by the factor MUDEF as the ratio of
      doses inside the cell with and without AuNP. RESULTS: Maps of ionization density
      were obtained at the central plane of the cell illustrating ionizations around
      and between AuNP. The density of ionization increases in cell medium as the AuNP
      diameter enlarges, being higher to larger nanoparticles for all energies studied.
      The total dose deposited in the cell is affected by the fraction of electrons
      consumed in the nanoparticles, resulting in size-dependence for MUDEF. The MUDEFs
      for 250kV are 1.68 to 20nm, 1.83 to 60nm and 1.72 to 100nm; MUDEFs for 6MV are
      1.14 to 20nm, 1.38 to 60nm and 1.20 to 100nm, therefore presenting an optimum
      nanoparticle size for clinical applications in Radiation Therapy. CONCLUSIONS:
      The MUDEF describes dose enhancements founded on the effective density of
      ionizations inside cell medium containing AuNP, considering real electron tracks
      close to metallic interfaces. The profile of ionizations describes electron
      spectra of electrons with intracellular range considering dynamics of creation
      and consumption, hence being directly proportional to potential applicability of
      AuNP in Radiation Therapy. This work was funding supported by CAPES - Nanobiomed
      Network.

PMID- 28518264
TI  - MO-D-BRB-04: The Approval Process for the Use of Proton Therapy in NCI-Sponsored
      Clinical Trials.
AB  - PURPOSE: To describe the approval process for the use of proton therapy in NCI-
      sponsored clinical trials. METHODS: The RPC has developed a comprehensive system
      for the approval of proton therapy centers for participation in clinical trials.
      The approval process includes: 1) completion of the proton facility
      questionnaire, 2) participation in the RPC's annual TLD remote audit program, 3)
      electronic submission of treatment planning data to the Image-Guided Therapy
      Center (ITC), and 4) successful completion of an on-site dosimetry review visit,
      including the irradiation of two of the RPC's anthropomorphic proton phantoms
      (prostate and spine). The on-site audits allow the RPC to review the
      institution's treatment planning process, from simulation to treatment delivery,
      as well as their quality assurance practices. The RPC performs a complete set of
      measurements that tests the CT simulator's CT# vs. RSP conversion curve,
      treatment planning data, on-board imaging, and treatment delivery. These
      measurements detect gross errors that might lead to inaccurate proton dose
      delivery. The review of the institutions' QA procedures allows the RPC to
      encourage all proton centers to maintain a consistent level of periodic
      monitoring of their proton therapy delivery. Upon completion of the visit, a full
      report is written detailing the results from the visit, phantom irradiation, and
      recommendations for improving their treatment delivery and QA. RESULTS: To date,
      the RPC has approved seven proton therapy centers for the use of scattered or
      uniform scanning proton treatment delivery in clinical trials. Results of the
      phantom irradiations have identified an error in the HU vs RLSP curve. The site
      visits have identified several lapses in QA procedures, inappropriate HU vs RLSP
      values, and weaknesses in treatment planning. CONCLUSIONS: The RPC's proton
      therapy approval process has been developed and has identified areas of
      improvement for proton centers to use proton therapy in clinical trials. Work
      supported by grants CA10953, CA059267, and CA81647 (NCI, DHHS).

PMID- 28518265
TI  - MO-D-213CD-03: Advanced Angiographic Imaging Techniques.

PMID- 28518266
TI  - MO-A-BRB-04: Treatment Plan Data Collection, Beam Modeling and Clinical
      Validation for Unfiattened Beams.
AB  - : The use of an unfiattened photon beam for radiotherapy treatment is a new
      concept in the Radiation Oncology field. In the past, the non-optimal radiation
      area coverage obtained with unfiattened photon beams was of concern, and the
      flattening filter was introduced to overcome this pitfall. With the advance of
      technology, Intensity Modulated Radiotherapy (IMRT) emerged and non-optimal
      coverage was no longer an issue since the beam intensity could be modulated to
      obtain the desired target coverage. Unfiattened photon beams offer several
      advantages over flattened beams, namely: (1) they provide 2 to 4 times the dose
      rate, which significantly shortens the treatment time, especially for the high
      dose irradiation techniques, (2) they provide a purer beam spectrum, which is
      easier to model in a treatment planning system, (3) the head scatter is
      dramatically reduced, giving a lower dose outside of the field and (4) they
      provide a sharper penumbra, which makes planning easier. This lecture will
      provide an overview of the data collection, the treatment planning system (TPS)
      parameter modeling and the TPS validation for clinical implementation of
      unfiattened photon beams. LEARNING OBJECTIVES: 1. Understand the physics data
      collection and related issues. 2. Understand the TPS parameter modeling, planning
      validation and related issues. 3. Understand the optimal usage of unfiattened
      beams with clinical examples.

PMID- 28518267
TI  - MO-D-217BCD-01: Personalizing Medicine: Adapting to the Individual.
AB  - : Personalizing medicine through patient-specific adaptation is quickly moving
      from retrospective research to clinical implementation. The commercial
      availability of clinical tools, including auto-segmentation, deformable
      registration, and dose accumulation, is enabling these techniques to be utilized
      more efficiently. Understanding the importance, rationale, and consequences of
      anatomical and physiological based adaptation is paramount for the safe
      implementation of these techniques. This includes accounting for radiobiological
      differences in delivered dose and the impact that this may have on tumor control
      and normal tissue response. This interactive session will highlight the evidence
      and rationale for anatomy-based adaptation, including retrospective studies from
      several anatomical sites indicating the uncertainties between the planned and
      delivered dose and the benefits achievable through adaptation. Translation of
      these techniques into the clinic will be discussed. The growing use of functional
      imaging enables more sophisticated adaptation and personalization of the
      treatment plan based on an understanding of the individual response of the tumor
      and normal tissue to radiation. Methods to understand and incorporate this
      information into the patient treatment plan will be discussed. The
      radiobiological impact of dose accumulation methods and adaptive strategies is
      often overlooked. Biological factors and their influence on these adaptive
      strategies will be addressed. The clinician's perspective will also be
      highlighted, including the benefits of dose accumulation, personalization, and
      adaptation for the patient and the impact that this technology may have on
      clinical trials and outcomes assessment. LEARNING OBJECTIVES: 1. Understand the
      need for anatomy-based adaptation and methods to safely implement this in the
      clinic 2. Recognize the need for physiological-based adaptation and methods to
      safely implement this into the clinic 3. Appreciate the radiobiological
      limitations and concerns associated with dose summation, and adaptation 4.
      Describe the clinical implications of dose summation and adaptation on individual
      patient treatments, clinical trials, and outcomes assessment.

PMID- 28518268
TI  - MO-D-BRB-08: BEST IN PHYSICS (THERAPY) - A Real Time Dose Monitoring and Dose
      Reconstruction Tool for Patient Specific VMAT QA and Delivery.
AB  - PURPOSE: To develop a real time dose monitoring and dose reconstruction tool to
      identify and quantify sources of errors during patient specific VMAT delivery and
      QAMethods: The VMAT delivery monitor tool called Linac Data Monitor (LDM) has
      been developed that connects to the linac in clinical mode and displays, records
      and compares real-time machine parameters to the planned parameters. A new
      quantity called integral error keeps a running total of leaf overshoot and
      undershoots errors in each leaf pair multiplied by leaf width and the amount of
      time during which error exists in MU delivery. Another tool reconstructs pinnacle
      format delivered plan based on the saved machine logfile and recalculates actual
      delivered dose in patient anatomy. Delivery characteristics of various standard
      and hypofractionation VMAT plans delivered on Elekta Axesse and Synergy linacs
      were quantified. RESULTS: The MLC and gantry errors for all the treatment sites
      were 0.00+/-0.59mm and 0.05+/-0.31 degrees , indicating a good MLC gain
      calibration. Standard fractionation plans had a larger gantry error than
      hypofractionation plans due to frequent dose rate changes. On average the MLC
      errors were negligible but larger errors of 4-6 mm and 2.5 degrees  were seen
      when dose rate varied frequently. Large gantry errors occurred during the
      acceleration and deceleration process, and correlated well with MLC errors
      (p<0.0001). PTV mean, minimum, maximum dose discrepancy were 0.87+/-0.21%, 0.99+/
      0.59% and 1.18+/-0.52%. The other OAR doses were within 2.5% except a few that
      showed up to 5.6% discrepancy in maximum dose. Realtime displayed normalized
      total positive integral error (normalized to the total MUs) correlated linearly
      with MLC and gantry errors (p<0.001) and dosimetric discrepancy (PTVmean: p<0.01;
      PTVmax: p<0.067 and PTVmax: p<0.046). CONCLUSIONS: Errors may exist during
      complex VMAT planning and delivery. LDM is capable of detecting and quantifying
      mechanical and dosimetric errors at various stages of planning and delivery.

PMID- 28518269
TI  - MO-F-213AB-05: Commissioning of Gated RapidArc Radiotherapy for Treatment of
      Moving Targets.
AB  - PURPOSE: To commission and evaluate gated RapidArc radiotherapy of a linear
      accelerator (Varian TrueBeam) for treatment of moving targets using a
      programmable dynamic phantom. METHODS: The phantom used had different dosimetry
      inserts for measurement of dose and dose distribution. It could be programmed to
      move in the anterior-posterior and superior-inferior axes with different motion
      patterns, amplitudes and frequencies to simulate lung motions of patients. A set
      of 4D CT images was acquired with the aid of a Varian RPM system. Images acquired
      at the 40, 50 and 60% of the motion cycle were selected and transferred to a
      treatment planning system (Varian Eclipse) for planning. A two-arc RapidArc
      treatment plan was generated for a C-shaped target volume with a conformity index
      of 1.49 and transferred to the TrueBeam for treatment delivery. Dose and dose
      distribution measurements were performed using a 0.057 cc ionization chamber and
      radiochromic films, respectively and compared with the TPS calculations. Five
      treatment fractions were given in three days with two different target motion
      patterns to assess the consistency of the dose delivery. RESULTS: Agreement
      between TPS calculation and measurement were within 1.64% for dose and 3% or 3mm
      in distance to agreement for dose distribution. Repeatability of dose delivery
      between treatments was within 0.1% (1SD) in the five treatment fractions
      delivered in three days. The time required to deliver a dose of 2 Gy to a moving
      C-shaped target using gated RapidArc technique with two gantry rotations was
      about 15 minutes. CONCLUSIONS: The geometric and dosimetric accuracy and
      consistency of gated RapidArc radiotherapy had been verified. Our study indicated
      that the accuracy and consistency of the treatment modality were acceptable for
      clinical implementation.

PMID- 28518271
TI  - MO-E-BRCD-01: Proton Treatment Planning Issues.
AB  - : Proton treatment planning involves many issues that affect the accuracy and
      robustness of treatment planning and delivery. Some issues such as patient setup
      uncertainty and CT number calibration are common with photon planning but have
      potentially greater effects on the treatment plan simulation and delivery for
      proton. Other issues such as range uncertainty and LET and RBE variations are
      unique to particle therapy. The complications of proton treatment planning have
      been well documented in the literature but there are multiple planning methods
      developed by clinics to reduce or avoid proton dosimetry errors in treatment
      delivery. Additionally, error reduction methods are dependent upon the delivery
      Method: scattering or scanning, single-field optimization or multi-field
      optimization. This educational session will discuss the documented proton
      treatment planning issues and the methods developed in three different clinical
      centers to minimize or eliminate the errors associated with the issues for
      various treatment sites and proton treatment modalities. LEARNING OBJECTIVES: 1.
      Understand the issues associated with proton treatment planning and the effects
      of range uncertainty, LET variations, and setup uncertainties. 2. Understand the
      differences of photon and proton treatment planning issues. 3. Understand the
      methods developed to reduce errors in proton treatment planning and delivery at
      three different centers.

PMID- 28518272
TI  - MO-F-BRB-01: Extracting Material Information from the CT Numbers by Artificial
      Neural Network for Use in the Monte Carlo Simulations of Tissues in
      Brachytherapy.
AB  - PURPOSE: The Artificial Neural Networks (ANNs) are useful in solving nonlinear
      processes, without the need to mathematical models of the parameters. Since the
      relationship between the CT numbers and material compositions is not linear, we
      can use the AANs for tissue density calibration. The aim of this study is to
      obtain the composition and mass density of different tissues which are necessary
      in Monte Carlo simulation of different tissues in brachytherapy treatment
      planning using ANNs. METHODS: The ANNs were used for mass density calibration.
      First, the density and composition of several tissues of the body, along with
      their corresponding CT numbers are used as the training samples. After the
      network is trained, it would give us the material information, i.e. mass density,
      and material composition corresponding to each CT numbers. The tissue
      compositions and densities predicted by the ANN for each CT number, were compared
      with the real values of such parameters. The tissue parameters predicted by the
      ANN were used as the phantom materials for obtaining the dose at different
      distances from Pd-103, and Cs-137 brachytherapy sources. Finally the dose at
      different distances of the real phantoms were compared with dose around the
      phantoms predicted by ANN. RESULTS: The ANN used in this study, can predict the
      material compositions of different tissues precisely. For example, it can give
      the mass densities of bone, water, and muscle with the percentage differences of
      0.62%, - 1.1%, and 0.33% respectively. Comparing the dose distribution inside the
      water phantom predicted by Artificial Neural Networks and the real water phantom,
      shows the percentage difference of less than 0.7% and 2% for Cs-137 and Pd-103
      respectively. CONCLUSIONS: The ANNs are applicable in determination of tissue
      parameters from the CT images data, and the material compositions and density
      obtained by this methods can be used for material definition in Monte Carlo
      simulations.

PMID- 28518273
TI  - MO-D-213AB-01: A Brief History of Medical Physics Reimbursement.
AB  - : "Corporate memory" is important in many areas of medical physics, but
      especially so in the area of economics. To appreciate where medical physics
      currently resides in the reimbursement arena, it is imperative that we know from
      whence we came. This talk will trace the history of medical physics
      reimbursement, chiefly in the area of radiation oncology since most of our
      reimbursement codes appear in that clinical specialty. We will begin with the
      initiation of the Harvard RBRVS system and the effect it had on our field.
      Subsequently, we will trace the impact of new technological advances in the field
      and how, at each juncture, the reimbursement associated with these advances
      directly impacted our employment opportunities and salaries. Although much of the
      operations of the three chief panels associated with health care reimbursement,
      the Current Procedural Terminology (CPT) Editorial Panel, the Relative-Value
      Update Committee (RUC) and the Centers for Medicare and Medicaid Services (CMS)
      are confidential in nature, the history of how these panels operate and their
      impact on how health care is reimbursed is important to our field. For those of
      us who have labored in this arena over the years, there are successes and
      failures as new procedures in radiation oncology were taken for reimbursement
      consideration, initially by the Joint Economics Committee of ACR and ASTRO, and
      later by ASTRO in collaboration with AAPM. These will be discussed in a general
      sense to avoid confidentiality breaches. As we progressed from the use of CT
      planning images with 3D conventional therapy, brachytherapy -high and low dose
      rate systems, IMRT planning and delivery (with concomitant plan verification
      work) to the latest procedures of SRS and SBRT with Image Guided Radiation
      Therapy (IGRT), each procedure has its own story surrounding how its
      reimbursement was developed. Where no confidentiality issues are involved, the
      stories behind the scenes will be discussed as these procedures were taken
      forward in the reimbursement process. Going forward, changes in how we are
      reimbursed for our services will inevitably occur. For our imaging colleagues,
      their work will still be classed as a cost center for their departments. AAPM PEC
      is evaluating how they can begin being reimbursed with explicit CPT codes, but
      this will take some effort. LEARNING OBJECTIVES: 1. Understand where medical
      physics reimbursement came from in radiation oncology 2. Understand the
      arrangement of our societies and interaction with reimbursement entities 3.
      Understand how medical physics workforce and remuneration for services is
      structured 4. Understand what the future may bring in medical physics
      reimbursement.

PMID- 28518270
TI  - MO-F-BRA-02: Evaluation of 4D CT to 4D Cone-Beam CT Deformable Image Registration
      for Lung Cancer Adaptive Radiation Therapy.
AB  - PURPOSE: To evaluate two deformable image registration (DIR) algorithms for the
      purpose of contour mapping to support image guided adaptive radiotherapy (IGART)
      with 4D cone beam CT (4DCBCT). METHODS: Eleven locally advanced non-small cell
      lung cancer (NSCLC) patients underwent one planning 4D fan- beam CT (4DFBCT) and
      seven weekly 4DCBCT scans. Gross tumor volume (GTV) and carina were delineated by
      a physician in all 4D images. For day to day registration, the end of inspiration
      4DFBCT phase was deformably registered to the corresponding phase in each 4DCBCT
      image. For phase to phase registration, the end of inspiration phase from each 4D
      image was registered to end of expiration phase. The delineated contours were
      warped using the resulting transforms and compared to the manual contours through
      Dice similarity coefficient (DSC), false positive and false negative indices,
      and, for carina, target registration error (TRE). Two DIR algorithms were tested:
      1) small deformation, inverse consistent linear elastic (SICLE) algorithm and 2)
      Insight Toolkit diffeomorphic demons (DEMONS). RESULTS: For day to day
      registrations, the mean DSC was 0.59 +/- 0.16 after rigid registration, 0.72 +/-
      0.13 with SICLE and to 0.66 +/- 0.18 with DEMONS. SICLE and DEMONS reduced TRE to
      4.1 +/- 2.1 mm and 5.8 +/- 3.7 mm respectively, from 6.2 +/- 3.5 mm; and reduced
      false positive index to 0.27 and 0.26 respectively from 0.46. Registration with
      the cone beam as the fixed image resulted in higher DSC than with the fan beam as
      fixed (p < 0.001). SICLE and DEMONS increased the DSC on average by 10.0% and
      8.0% and reduced TRE by 2.8 mm and 2.9 mm respectively for phase to phase DIR.
      CONCLUSIONS: DIR achieved more congruent mapping of target structures to
      delineations than rigid registration alone, although DIR performance varied with
      algorithm and patient. This work was supported by National Cancer Institute Grant
      No. P01 CA 116602.

PMID- 28518275
TI  - MO-F-213AB-02: Correcting Spread-Out Bragg Peak Slope Using Time-Resolved Monte
      Carlo Simulations and Beam Current Modulation.
AB  - PURPOSE: To fully characterize the spread-out Bragg peak from the Mevion S250
      Proton Therapy System using Monte Carlo simulations, evaluate the slope of the
      spread-out Bragg peak in the treatment field, and correct this slope by virtually
      applying beam current modulation. METHODS: MCNPX simulations were performed on
      the Mevion S250 for each of the 24 beamline configurations, with the modulator
      wheel rotated in 1 degree increments. Energy deposition was tallied in a water
      phantom, resulting in 8,640 central axis depth-dose calculations. These data were
      imported into MATLAB and the slope of the spread-out Bragg peak (SOBP) was
      evaluated for a constant beam current. An iterative algorithm was developed to
      determine the optimal beam current modulation (BCM) profile as a function of
      modulator wheel position for each configuration. These BCM profiles were then
      applied virtually to the MCNPX SOBP data and slope values were recalculated for
      the optimized SOBP profiles. RESULTS: Ideally SOBP slope would measure 0.0 %/cm
      in the treatment field, corresponding to a uniform dose delivery. Prior to BCM
      correction, slopes between -1.0 and +2.0 %/cm were observed across all beamline
      configurations. These were reduced to +/-0.2 %/cm by applying optimized BCM
      profiles. The algorithm converged quickly, validating its underlying assumption
      that the optimal SOBP profile can be determined by considering only a single dose
      values at the depths of maximum individual Bragg peak dose. CONCLUSIONS:
      Optimized BCM profiles adequately reduce SOBP slope in the treatment field, and
      may be further studied using time-resolved MCNPX simulations. The algorithm
      presented efficiently calculates BCM profiles, fully accounting for beamline
      scatter and partial-shining effects across adjacent steps on the range modulator
      wheels, and without requiring direct measurements. Future work includes applying
      this same algorithm to optimize the SOBP distal dose profile. Partially supported
      by MEVION Medical Systems, Inc.

PMID- 28518274
TI  - MO-D-BRB-10: Modeling Inter-Patient Variation of Organ-At-Risk Sparing in IMRT
      Plans: An Evidence-Based Plan Quality Evaluation.
AB  - PURPOSE: To develop a predictive model to assess the quality of critical organ
      dose sparing in IMRT plans by providing patient specific dose sparing references,
      based on an array of patient anatomical features and prior planning experience.
      METHODS: Contributions of various patient anatomical features to the inter
      patient OAR dose sparing variation in IMRT planning were systematically studied
      using machine learning method based on high quality prior plans. The dependence
      of anatomical factor on OAR dosimetric parameters is formulated into predictive
      models. The OAR dosimetric parameters generated by these predictive models
      represent the "best feasible" clinical outcomes based on past planning
      experiences. IMRT plans of 88 prostate, 106 head-and-neck (HN) and 21 spine SBRT
      treatments were used to train the models. The final models were tested by
      additional 24 prostate and 48 HN plans. The model for spine SBRT was tested by
      the leave-one-out method. RESULTS: For HN and prostate planning, the significant
      patient anatomical features that affect OAR sparing are: the distance between OAR
      and PTV, the portion of OAR volume within an OAR specific distance range, the
      overlap volume between OAR and PTV, and the portion of OAR volume outside the
      primary treatment field. For spine SBRT planning, the most significant patient
      anatomical feature that affects cord sparing is the tightness of the geometric
      enclosure of PTV surrounding the cord and the homogeneity of PTV dose coverage.
      The dosimetric parameters predicted for the test patient cases using the models
      were in agreement with those from the clinical plans in more than 75% of the
      cases. CONCLUSIONS: The developed predictive models indicated substantial
      correlation between some important patient anatomical features and OAR dose
      sparing based on expert experiences. These models can be used as effective tools
      for evaluating the quality of treatment plans customized to individual patient's
      anatomy. Partially supported by a master research agreement with Varian Medical
      System, Inc.

PMID- 28518277
TI  - MO-F-BRB-05: Monte Carlo Modeling of the Novalis TX Stereotactic Radiosurgery
      Mode.
AB  - PURPOSE: To model the stereotactic mode of the Varian-Brainlab Novalis TX linear
      accelerator using the BEAMnrc Monte Carlo user code Methods: The EGSnrc Monte
      Carlo user codes BEAMnrc and DOSXYZnrc were used for photon simulations and dose
      calculations, respectively. A Monte Carlo model of a Varian Clinac 21 EX was
      modified to model the stereotactic radiosurgery (SRS) mode of the Novalis, taking
      into account the smaller dimensions of the SRS flattening filter and limited
      field sizes. The parameters of source such as energy, size and angular spread,
      were readjusted following a new procedure outlined by Almberg et al, 2012. A
      component module, DYNVMLC, previously used to model the Varian Millennium 120
      multi-leaf collimator (MLC), was reprogrammed to include the four leaf types of
      the Varian high definition 120 leaf MLC. Interleaf air-gap and leaf density were
      adjusted to match interleaf leakage profiles measured with EBT2 film. Subsequent
      validation included profiles, percent depth dose curves and output factors
      measured with ion chambers, and other film measurements. RESULTS: From PDD
      measurements, the energy of the incident electron beam was determined to be 6.6
      MeV. From penumbra measurements, the electron radial intensity distribution,
      given as the full width at half maximum of a Gaussian distribution, was found to
      be 0.7 mm (cross-plane) and 0.8 mm (in-plane). From profiles in water, the mean
      angular spread had to be adjusted to 1.27 degrees  to achieve an acceptable
      match. The interleaf air-gap and the density of the leaves of the HDMLC were
      determined to be 0.0047 cm and 18.5 g/cm3 , respectively. CONCLUSIONS: The
      Almberg procedure was successfully implemented in determining the electron beam
      parameters to model the Novalis Tx's SRS mode. Dose profiles simulated with the
      new HDMLC component module agreed with measurements within 2%.

PMID- 28518276
TI  - MO-B-211-01: Linac-Based IMRT/VMAT Commissioning and QA Program Development.
AB  - : Intensity modulated radiotherapy (IMRT) has been used clinically for many
      years. Reports from the RPC indicate that up to 30% of the institutions fail to
      pass RPC IMRT credentialing process on the first attempt. While volumetric
      modulated arc therapy (VMAT) has been introduced more recently, it has quickly
      gained wide clinical use. In spite of the long history with IMRT and rapid
      adoption of VMAT, commissioning and developing a quality assurance (QA) program
      continues to be a challenge especially in busy departments. These points indicate
      that a review of commissioning and quality assurance for IMRT is still very much
      needed. In this session, the development of an overall IMRT/VMAT QA program, the
      role of team members and on-going program functions will be described including
      aspects of both quality and safety. General issues and specifics of IMRT/VMAT
      commissioning and quality assurance will be covered. While the general principles
      of commissioning and QA apply to any device capable of intensity-modulation,
      specific examples will be provided for Elekta and Varian linear accelerators.
      Strategies for commission and useful checklists will be discussed as well as some
      differences between Elekta and Varian technologies. There will also be a focus on
      practical advice towards the implementation and on-going QA of linac-based IMRT
      and VMAT. Patient- specific QA strategies along with the comparison of different
      QA equipment and techniques will be presented. Lastly, differences will be
      highlighted between IMRT and VMAT for patient-specific QA. LEARNING OBJECTIVES:
      1. Understand approaches to IMRT/VMAT commissioning and QA 2. Describe most
      relevant issues in patient-specific QA for IMRT/VMAT 3. Discuss issues with IMRT
      /VMAT QA equipment and techniques.

PMID- 28518278
TI  - MO-D-BRB-03: Comparison of Proton Therapy Institutional Data Collected by the
      RPC.
AB  - PURPOSE: To detail and compare data collected during RPC onsite dosimetry review
      visits at proton therapy centers. METHODS: The RPC has established a complete
      review process for proton therapy institutions wishing to participate in NCI
      funded clinical trials that includes an on-site dosimetry review visit performed
      by the RPC. During the visit, the RPC takes measurements that include CT# vs.
      relative stopping power (RSP) conversion, beam output, depth dose, lateral
      profiles, QA procedure reviews and anthropomorphic phantom irradiations. The RPC
      reviewed beam output, depth dose and lateral profiles for 5 specific anatomic
      treatment sites, reference, prostate, lung, brain, and spine as compared to the
      institution's measured or treatment planning-derived values. In addition, the RPC
      has compared results from each institution's proton prostate phantom irradiation.
      RESULTS: All of the institutions visited had RPC/Institution output ratios that
      ranged between 0.95 - 1.02 where the acceptance criterion was +/-5%. For the CT#
      to RSP comparison, there was a larger variability. Only two institutions agreed
      within five percent of the recommended values, while the other five institutions
      had disagreements of up to 20 percent in the high density (high CT number) region
      of the conversion curve that may have a clinical impact on dose delivery. For the
      prostate phantom irradiation, 3 institutions failed to meet the RPC's +/-7%/4mm
      acceptance criteria on the initial attempt, but in the end all 7 sites met the
      criteria. CONCLUSIONS: The proton beam output for 7 proton centers, as measured
      by the RPC, is comparable (+/-5%), however, there are large discrepancies in the
      CT# vs RSP conversion curves used from institution to institution. As a result of
      the RPC onsite dosimetry review visits, several institutions have modified their
      procedures and dosimetry parameters to improve proton therapy delivery for NCI
      funded clinical trials. Work supported by grants CA10953, CA059267, and CA81647
      (NCI, DHHS).

PMID- 28518279
TI  - MO-D-213CD-02: Non-Contrast-Enhanced Magnetic Resonance Angiography Methods for
      Assessment of Morphology and Flow.
AB  - : Traditional clinical MR Angiography (MRA) provides volumetric datasets to
      characterize the vessel lumen. These MRA techniques can be generally separated
      into two categories: * contrast-enhanced MRA, which requires the venous injection
      of a paramagnetic contrast agent in form of a Gadolinium chelate and * non
      contrast-enhanced MRA (NCE MRA), which relies on signal properties of the blood
      or the motion of the blood to create signal differences between the blood pool
      and the surrounding tissues. Time-of-Flight (TOF) and Phase- Contrast (PC)
      imaging have been developed as NCE techniques in the early days of MR imaging.
      However, widespread clinical adaptation of MRA did not occur until the
      introduction of CE-MRA in the mid-1990ies with significantly improved robustness.
      Recent developments have renewed the interest in imaging approaches that do not
      rely on any external contrast agents. Advances in hardware, especially gradient
      amplifiers and multi-channel coil technology, have reduced imaging times,
      improved the signal-to-noise ratio, and reduced artefacts so that NCE MRA is
      becoming competitive again. These approaches provide viable alternatives in
      patients that are at risk for nephrogenic systemic fibrosis (NSF) and should not
      receive a Gd-based contrast agent. In addition, some of those approaches provide
      insights in functional information beyond the standard luminography. For example,
      arterial spin labeling (ASL) imaging can be used as a 'pseudo arterial injection'
      by labeling blood in targeted volumes and tracking its distribution over time.
      Novel '4D MR Flow' imaging is an extension of traditional PC MRA to capture
      volumetric velocity vector fields throughout the cardiac cycle, thereby allowing
      for direct measures of hemdodynamic parameters such as pressure gradient, wall
      shear stress, pulse wave velocity, kinetic energy, and more. This lecture will
      provide an overview of the underlying contrast mechanisms of time-of-flight,
      phase-contrast, balanced steady state free precession (bSSFP), and ASL MRA.
      Current and potential future roles of these approaches in clinical imaging will
      also be discussed. LEARNING OBJECTIVES: 1. Understand the various origins of MRA
      contrast mechanisms that do not require a contrast agent. 2. Understand the
      issues related to NCE-MRA imaging including design, acquisition and processing.
      3. Understand the benefits, pitfalls, and future potentials of these approaches.
      My research is sponsored by GE Healthcare.

PMID- 28518280
TI  - MO-C-BRCD-03: The Role of Informatics in Medical Physics and Vice Versa.
AB  - : Like Medical Physics, Imaging Informatics encompasses concepts touching every
      aspect of the imaging chain from image creation, acquisition, management and
      archival, to image processing, analysis, display and interpretation. The two
      disciplines are in fact quite complementary, with similar goals to improve the
      quality of care provided to patients using an evidence-based approach, to assure
      safety in the clinical and research environments, to facilitate efficiency in the
      workplace, and to accelerate knowledge discovery. Use-cases describing several
      areas of informatics activity will be given to illustrate current limitations
      that would benefit from medical physicist participation, and conversely areas in
      which informaticists may contribute to the solution. Topics to be discussed
      include radiation dose monitoring, process management and quality control,
      display technologies, business analytics techniques, and quantitative imaging.
      Quantitative imaging is increasingly becoming an essential part of
      biomedicalresearch as well as being incorporated into clinical diagnostic
      activities. Referring clinicians are asking for more objective information to be
      gleaned from the imaging tests that they order so that they may make the best
      clinical management decisions for their patients. Medical Physicists may be
      called upon to identify existing issues as well as develop, validate and
      implement new approaches and technologies to help move the field further toward
      quantitative imaging methods for the future. Biomedical imaging informatics tools
      and techniques such as standards, integration, data mining, cloud computing and
      new systems architectures, ontologies and lexicons, data visualization and
      navigation tools, and business analytics applications can be used to overcome
      some of the existing limitations. LEARNING OBJECTIVES: 1. Describe what is meant
      by Medical Imaging Informatics and understand why the medical physicist should
      care. 2. Identify existing limitations in information technologies with respect
      to Medical Physics, and conversely see how Informatics may assist the medical
      physicist in filling some of the current gaps in their activities. 3. Understand
      general informatics concepts and areas of investigation including imaging and
      workflow standards, systems integration, computing architectures, ontologies,
      data mining and business analytics, data visualization and human-computer
      interface tools, and the importance of quantitative imaging for the future of
      Medical Physics and Imaging Informatics. 4. Become familiar with on-going efforts
      to address current challenges facing future research into and clinical
      implementation of quantitative imaging applications.

PMID- 28518281
TI  - MO-D-BRB-07: Failure-Mode and Effects Analysis Study for CyberKnife Stereotactic
      Radiosurgery.
AB  - PURPOSE: The purpose of this study is to conduct a Failure Modes and Effect
      Analysis (FMEA) for CyberKnife Stereotactic Radiosurgery to determine the
      sensitivity of existing QA procedures and determine in which areas new QA
      procedures needed to be implemented. METHODS: Members from each professional team
      providing service for CyberKnife radiosurgery (Medical Physicists, Nurses,
      Physicians, Radiation Therapists, and Administrators) were interviewed to gather
      potential failure modes. A patient flow chart was developed from patient consult
      to conclusion of last treatment. Failure modes were mapped to nodes in the flow
      charts to identify potential high-risk areas. A matrix was created to correlate
      existing QA procedures with failure modes to identify failure modes that were not
      covered by any QA as well as identify the sensitivity of QA procedures to prevent
      failures. RESULTS: 180 failure modes were identified. Current AAPM QA
      recommendations were found to focus preferentially on technical failure modes
      (15%), while the majority of failure modes found are process failures and human
      errors (85%). Creating a Venn diagram of CyberKnife and Gamma Knife failure modes
      revealed a large overlap area. The most effective QA checks are checklists for
      physics second chart review and pre- treatment time-out checklists. Existing
      checklists were modified and new checklists added to address high-ranked failure
      modes. New procedure guidelines, e.g. for contouring workflow and add-on
      simulations, were developed as QC to address clusters of failure modes. An ARIA
      CyberKnife DICOM interface is being implemented to resolve failure modes
      centering around multiple fraction, multiple plan treatments and total dose
      tracking. CONCLUSIONS: This work is the first FMEA study for the CyberKnife
      stereotactic radiosurgery. It will facilitate medical physicists using the
      CyberKnife to deliver SRS/SBRT treatments to transition from experience-based
      technical QA to a comprehensive new quality paradigm including technical,
      process, and human safety aspects.

PMID- 28518282
TI  - MO-D-218-01: Overview of Methodology and Standards (QIBA, IEC, AIUM and AAPM).
AB  - : Ultrasound system standards and professional guidelines can facilitate
      efficient provision of medical physics services and growth of ultrasound imaging
      if the documents are well designed and are utilized. We too often develop our own
      phantoms and procedures and never converge to obtain a critical mass of data on
      system performance and value of such services. Standards can also produce
      unnecessary costs and limit innovation if not carefully developed, reviewed, and
      changed as needed. There are quite a few new initiatives that, if followed
      vigorously, could improve medical ultrasound and medical physicists'
      contributions thereto. This talk is to explain many of the existing standards and
      recommendations for ultrasound system quality control, performance evaluation,
      and safety, as well as current and suggested efforts in these areas. The primary
      standards body for medical ultrasound systems is now the International
      Electrotechnical Commission (IEC). Uniformity across the world is helpful to all
      if the documents are reasonably current. There still is a role for traditional
      bodies such as the AAPM with its valuable report series and the American Inst. of
      Ultras. in Med. (AIUM) with its own standards and reports and its joint work with
      the Medical Imaging Technology Alliance (MITA). All three, with strong
      involvement of FDA scientists and with some efforts from the Acoustical Society
      of America have historically provided the main standards affecting medical
      physicists. Now that the lengthy IEC process is moving more smoothly, our
      national bodies still can provide new developments and drafts that can be offered
      as needed for international standardization. The ACR in particular can provide
      meaningful incentives through ultrasound service accreditation. Without any
      regulatory or strong consumer push, reports and standards on ultrasound system
      performance have received only modest use in the USA. A consistent consumer or
      accreditation push might be justified now. A series of three standards on
      performance evaluation is well on its way to covering pulse echo ultrasound well,
      with IEC 61319-1 on spatial measurements, IEC 61319-2 on depth of penetration and
      local dynamic range and one draft and one Technical Specification 62558 on small
      void imaging. A new effort has just been initiated to help drive more and better
      use of quantitative ultrasound imaging in human and surrogate studies and in
      clinical use. A shear wave speed ultrasound technical committee will carry out
      this effort in the Quantitative Imaging Biomarkers Alliance (QIBA) that is
      managed by the RSNA. LEARNING OBJECTIVES: 1. Understand the coverage of the two
      current and third planned IEC medical ultrasound performance evaluation standards
      that could form a basis for stable performance evaluation tests. 2. Understand
      the coverage of the Current AIUM and ACR QC documents and the drafting and
      support efforts in the IEC. 3. Understand the need for and partial availability
      of simplified software and instructions to improve and facilitate performance of
      these tests? 4. Understand how standards development can lead to improved
      understanding and performance of medical ultrasound imaging as is anticipated for
      the new QIBA effort.

PMID- 28518284
TI  - Molecular profiling as a novel tool to predict response to interferon-alpha2 in
      MPNs: The proof of concept in early myelofibrosis.

PMID- 28518283
TI  - Branched-chain amino acids for people with hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy is a brain dysfunction with neurological and
      psychiatric changes associated with liver insufficiency or portal-systemic
      shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic
      review including 11 randomised clinical trials on branched-chain amino acids
      (BCAA) versus control interventions has evaluated if BCAA may benefit people with
      hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful
      effects of BCAA versus any control intervention for people with hepatic
      encephalopathy. SEARCH METHODS: We identified trials through manual and
      electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      Embase, Science Citation Index Expanded and Conference Proceedings Citation Index
      - Science, and LILACS (May 2017). SELECTION CRITERIA: We included randomised
      clinical trials, irrespective of the bias control, language, or publication
      status. DATA COLLECTION AND ANALYSIS: The authors independently extracted data
      based on published reports and collected data from the primary investigators. We
      changed our primary outcomes in this update of the review to include mortality
      (all cause), hepatic encephalopathy (number of people without improved
      manifestations of hepatic encephalopathy), and adverse events. The analyses
      included random-effects and fixed-effect meta-analyses. We performed subgroup,
      sensitivity, regression, and trial sequential analyses to evaluate sources of
      heterogeneity (including intervention, and participant and trial
      characteristics), bias (using The Cochrane Hepato-Biliary Group method), small
      study effects, and the robustness of the results after adjusting for sparse data
      and multiplicity. We graded the quality of the evidence using the GRADE approach.
      MAIN RESULTS: We found 16 randomised clinical trials including 827 participants
      with hepatic encephalopathy classed as overt (12 trials) or minimal (four
      trials). Eight trials assessed oral BCAA supplements and seven trials assessed
      intravenous BCAA. The control groups received placebo/no intervention (two
      trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In
      15 trials, all participants had cirrhosis. We classed seven trials as low risk of
      bias and nine trials as high risk of bias (mainly due to lack of blinding or for
      profit funding). In a random-effects meta-analysis of mortality, we found no
      difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence
      interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of
      evidence). We found no evidence of small-study effects. Sensitivity analyses of
      trials with a low risk of bias found no beneficial or detrimental effect of BCAA
      on mortality. Trial sequential analysis showed that the required information size
      was not reached, suggesting that additional evidence was needed. BCAA had a
      beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827
      participants; 16 trials; high quality of evidence). We found no small-study
      effects and confirmed the beneficial effect of BCAA in a sensitivity analysis
      that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96).
      The trial sequential analysis showed that firm evidence was reached. In a fixed
      effect meta-analysis, we found that BCAA increased the risk of nausea and
      vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no
      beneficial or detrimental effects of BCAA on nausea or vomiting in a random
      effects meta-analysis or on quality of life or nutritional parameters. We did not
      identify predictors of the intervention effect in the subgroup, sensitivity, or
      meta-regression analyses. In sensitivity analyses that excluded trials with a
      lactulose or neomycin control, BCAA had a beneficial effect on hepatic
      encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses
      found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34
      to 1.30). AUTHORS' CONCLUSIONS: In this updated review, we included five
      additional trials. The analyses showed that BCAA had a beneficial effect on
      hepatic encephalopathy. We found no effect on mortality, quality of life, or
      nutritional parameters, but we need additional trials to evaluate these outcomes.
      Likewise, we need additional randomised clinical trials to determine the effect
      of BCAA compared with interventions such as non-absorbable disaccharides,
      rifaximin, or other antibiotics.

PMID- 28518405
TI  - Setting Ambitious yet Achievable Targets Using Probabilistic Projections: Meeting
      Demand for Family Planning.
AB  - In 2015, governments adopted 17 internationally agreed goals to ensure progress
      and well-being in the economic, social, and environmental dimensions of
      sustainable development. These new goals present a challenge for countries to set
      empirical targets that are ambitious yet achievable and that can account for
      different starting points and rates of progress. We used probabilistic
      projections of family planning indicators, based on a global data set and
      Bayesian hierarchical modeling, to generate illustrative targets at the country
      level. Targets were defined as the percentage of demand for family planning
      satisfied with modern contraceptive methods where a country has at least a 10
      percent chance of reaching the target by 2030. National targets for 2030 ranged
      from below 50 percent of demand satisfied with modern contraceptives (for three
      countries in Africa) to above 90 percent (for 41 countries from all major areas
      of the world). The probabilistic approach also identified countries for which a
      global fixed target value of 75 percent demand satisfied was either unambitious
      or has little chance of achievement. We present the web-based Family Planning
      Estimation Tool (FPET) enabling national decision makers to compute and assess
      targets for meeting family planning demand.

PMID- 28518345
TI  - Severe neonatal alloimmune thrombocytopenia caused by maternal sensitization
      against a new low-frequency alloantigen (Domb ) located on platelet glycoprotein
      IIIa.

PMID- 28518406
TI  - Host density increases parasite recruitment but decreases host risk in a snail
      trematode system.
AB  - Most species aggregate in local patches. High host density in patches increases
      contact rate between hosts and parasites, increasing parasite transmission
      success. At the same time, for environmentally transmitted parasites, high host
      density can decrease infection risk to individual hosts, because infective stages
      are divided among all hosts in a patch, leading to safety in numbers. We tested
      these predictions using the California horn snail, Cerithideopsis californica
      (=Cerithidea californica), which is the first intermediate host for at least 19
      digenean trematode species in California estuaries. Snails become infected by
      ingesting trematode eggs or through penetration by free-swimming miracidia that
      hatch from trematode eggs deposited with final-host (bird or mammal) feces. This
      complex life cycle decouples infective-stage production from transmission,
      raising the possibility of an inverse relationship between host density and
      infection risk at local scales. In a field survey, higher snail density was
      associated with increased trematode (infected snail) density, but decreased
      trematode prevalence, consistent with either safety in numbers, parasitic
      castration, or both. To determine the extent to which safety in numbers drove the
      negative snail-density-trematode-prevalence association, we manipulated
      uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh
      (California, USA). At each site, we quantified snail density and used data on
      final-host (bird and raccoon) distributions to control for between-site variation
      in infective-stage supply. After three months, overall trematode infections per
      cage increased with snail biomass density. For egg-transmitted trematodes, per
      snail infection risk decreased with snail biomass density in the cage and
      surrounding area, whereas per-snail infection risk did not decrease for
      miracidium-transmitted trematodes. Furthermore, both trematode recruitment and
      infection risk increased with infective-stage input, but this was significant
      only for miracidium-transmitted species. A model parameterized with our
      experimental results and snail densities from 524 field transects estimated that
      safety in numbers, when combined with patchy host density, halved per capita
      infection risk in this snail population. We conclude that, depending on
      transmission mode, host density can enhance parasite recruitment and reduce per
      capita infection risk.

PMID- 28518407
TI  - NAD+ : A big player in cardiac and skeletal muscle remodeling and aging.
AB  - In the past decade, NAD+ has gained importance for its beneficial effects as
      antioxidant and anti-aging molecule. A paper in science by Zhang et al. () has
      described that NAD+ when replenished, ameliorates muscle dystrophy in mice by
      improving mitochondrial function. NAD+ was also demonstrated by the authors to
      improve the life span of mice. Cox et al. () demonstrated the cardiac effects of
      NAD+ which mitigated chronic heart failure via mitochondrial redox state
      mechanism. Cox et al. () also demonstrated that NAD+ is provided in the drinking
      water, it improves cardiac relaxation in volume overload model of heart failure.
      Although NAD+ has a profound anti-aging and anti-oxidant effects, its effect on
      humans and use as a dietary supplement needs more exploration.

PMID- 28518408
TI  - S-Adenosylmethionine-mediated apoptosis is potentiated by autophagy inhibition
      induced by chloroquine in human breast cancer cells.
AB  - The naturally occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an
      ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous
      methylation reactions. In recent years, it has been shown that AdoMet possesses
      antiproliferative properties in various cancer cells, but the molecular
      mechanisms at the basis of the effect induced by AdoMet have been only in part
      investigated. In the present study, we found that AdoMet strongly inhibited the
      proliferation of breast cancer cells MCF-7 by inducing both autophagy and
      apoptosis. AdoMet consistently enhanced the levels of the autophagy markers
      beclin-1 and LC3B-II, and caused a significant increase of pro-apoptotic Bax/Bcl
      2 ratio paralleled by poly (ADP ribose) polymerase (PARP) and caspase 9, and 6
      cleavage. Notably, AdoMet, already at low doses, raised the percentage of cells
      in G2 /M phase of cell cycle by down-regulating the expression of cell cycle
      regulatory proteins cyclin B and cyclin E with a remarkable increase of p53, p27,
      and p21. We also evaluated the combination of AdoMet and the autophagy inhibitor
      chloroquine (CLC) showing that autophagy block is synergistic in inducing both
      growth inhibition and apoptosis. These effects were paralleled by a strong
      inhibition of the activity of AKT and of the downstream effector mTOR and by an
      increased cleavage of caspase-6 and PARP. These data suggest, for the first time,
      that autophagy can act as an escape mechanism from the apoptotic activity of
      AdoMet, and that AdoMet could be used in combination with CLC or its analogs in
      the treatment of breast cancer.

PMID- 28518409
TI  - Metabolic nodal response as a prognostic marker after neoadjuvant therapy for
      oesophageal cancer.

PMID- 28518411
TI  - Multicentre observational study of adherence to Sepsis Six guidelines in
      emergency general surgery.

PMID- 28518410
TI  - Meta-analysis of adjuvant therapy following curative surgery for periampullary
      adenocarcinoma.
AB  - BACKGROUND: Periampullary cancers are uncommon malignancies, often amenable to
      surgery. Several studies have suggested a role for adjuvant chemotherapy and
      chemoradiotherapy in improving survival of patients with periampullary cancers,
      with variable results. The aim of this meta-analysis was to determine the
      survival benefit of adjuvant therapy for periampullary cancers. METHODS: A
      systematic review was undertaken of literature published between 1 January 2000
      and 31 December 2015 to elicit and analyse the pooled overall survival associated
      with the use of either adjuvant chemotherapy or chemoradiotherapy versus
      observation in the treatment of surgically resected periampullary cancer.
      Included articles were also screened for information regarding stage, prognostic
      factors and toxicity-related events. RESULTS: A total of 704 titles were
      screened, of which 93 full-text articles were retrieved. Fourteen full-text
      articles were included in the study, six of which were RCTs. A total of 1671
      patients (904 in the control group and 767 who received adjuvant therapy) were
      included. The median 5-year overall survival rate was 37.5 per cent in the
      control group, compared with 40.0 per cent in the adjuvant group (hazard ratio
      1.08, 95 per cent c.i. 0.91 to 1.28; P = 0.067). In 32.2 per cent of patients who
      had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were
      noted. Advanced T category was associated worse survival (regression coefficient 
      0.14, P = 0.040), whereas nodal status and grade of differentiation were not.
      CONCLUSION: This systematic review found no associated survival benefit for
      adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary
      cancer.

PMID- 28518413
TI  - Spanish translation section.

PMID- 28518414
TI  - Systematic review of surgical and medical treatment for tertiary
      hyperparathyroidism.
AB  - BACKGROUND: A significant proportion of patients with chronic kidney disease and
      secondary hyperparathyroidism (HPT) remain hyperparathyroid after kidney
      transplantation, a state known as tertiary HPT. Without treatment, tertiary HPT
      can lead to diminished kidney allograft and patient survival. Parathyroidectomy
      was commonly performed to treat tertiary HPT until the introduction of the
      calcimimetic drug, cinacalcet. It is not known whether surgery or medical
      treatment is superior for tertiary HPT. METHODS: A systematic review was
      performed and medical literature databases were searched for studies on the
      treatment of tertiary HPT that were published after the approval of cinacalcet.
      RESULTS: A total of 1669 articles were identified, of which 47 were included in
      the review. Following subtotal and total parathyroidectomy, initial cure rates
      were 98.7 and 100 per cent respectively, but in 7.6 and 4 per cent of patients
      tertiary HPT recurred. After treatment with cinacalcet, 80.8 per cent of the
      patients achieved normocalcaemia. Owing to side-effects, 6.4 per cent of patients
      discontinued cinacalcet treatment. The literature regarding graft function and
      survival is limited; however, renal graft survival after surgical treatment
      appears comparable to that obtained with cinacalcet therapy. CONCLUSION: Side
      effects and complications of both treatment modalities were mild and occurred in
      a minority of patients. Surgical treatment for tertiary HPT has higher cure rates
      than medical therapy.

PMID- 28518415
TI  - Systematic review of transarterial embolization for hepatocellular adenomas.
AB  - BACKGROUND: Hepatocellular adenoma (HCA) larger than 5 cm in diameter is
      considered an indication for elective surgery, because of the risk of haemorrhage
      and malignant transformation. Transarterial embolization (TAE) is used to manage
      bleeding HCA and occasionally to reduce tumour size. TAE might have potential as
      an elective therapy, but its current role in this context is uncertain. This
      systematic review provides an overview of clinical outcomes after TAE, in
      bleeding and non-bleeding HCA. METHODS: Two independent reviewers performed a
      systematic search of literature in PubMed and Embase. Outcomes were change in
      tumour size, avoidance of surgery, complications and malignant transformation
      after TAE in bleeding and non-bleeding HCA. The Critical Appraisal Skills
      Programme tool for cohort studies was used for quality assessment of included
      studies. RESULTS: From 320 potential articles, 20 cohort studies and 20 case
      reports including 851 patients met the inclusion criteria. TAE was performed in
      151 of 851 patients (17.7 per cent), involving 196 tumours, of which 95 (48.5 per
      cent) were non-bleeding. Surgical treatment was avoided in 68 of 151 patients
      (45.0 per cent). Elective TAE was performed in 49 patients involving 66 HCAs,
      with 41 of these patients (84 per cent) not requiring surgery. Major
      complications occurred in eight of 151 patients (5.3 per cent); no death was
      reported. Among cohort studies, complete tumour disappearance was observed in 10
      per cent of patients, and regression in 75 per cent. CONCLUSION: Acute or
      elective TAE in the management of HCA is safe. In the elective setting, TAE
      provides a potential alternative to surgery.

PMID- 28518475
TI  - Lipid bodies accumulation in Leishmania infantum-infected C57BL/6 macrophages.
AB  - Lipid bodies (LBs) are intracellular accumulations of neutral lipids surrounded
      by a single membrane. These organelles are involved in the production of
      eicosanoids, which modulate immunity by either promoting or dampening
      inflammatory responses. Leishmania infantum, the etiological agent of visceral
      leishmaniasis in Brazil, is an intracellular parasite that causes disease by
      suppressing macrophage microbicidal responses. C57BL/6 mouse bone marrow-derived
      macrophages infected with L. infantum strain LcJ had higher numbers of LB+ cells
      (P<.0001) and total LBs than noninfected cultures. Large (>3 MUm) LBs were
      present inside parasitophorous vacuoles (PVs). These results contrast with those
      of L. infantum-infected BALB/c macrophages, in which the only LBs are derived
      from parasite, not macrophage origin. Increased LBs in C57BL/6 macrophages in
      close association with parasites would position host LBs where they could
      modulate L. infantum infection. These results imply a potential influence of the
      host genetics on the role of LBs in host-pathogen interactions. Overall, our data
      support a model in which the expression, and the role of LBs upon infection,
      ultimately depends on the specific combination of host-pathogen interactions.

PMID- 28518476
TI  - Adult-onset, chronic, cyclic thrombocytopenia in a Rhesus macaque (Macaca
      mulatta) after dengue virus vaccination and viral challenge.
AB  - An 8-year-old, male Rhesus macaque (Macaca mulatta), previously used for dengue
      virus (DENV) vaccine research with viral challenge, was presented with adult
      onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and
      function were evaluated by automated hematology, peripheral blood smears,
      electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was
      evaluated by cytology. Both serum anti-dengue nonstructural protein 1 (NS1)
      antibodies and anti-platelet antibodies were detected by ELISA. Platelet
      characterization showed a lack of aggregation to all agonists (ADP, ASP, and
      collagen), increased activation with increased expression of surface marker (HLA
      ABC), and an absence of surface receptor GPIX during clinical episodes of
      petechiae and ecchymoses, even in the presence of normal platelet counts. Bone
      marrow aspirates identified potential mild megakaryocytic hypoplasia. All
      platelet functions and morphologic attributes were within normal limits during
      clinically normal phases. Presence of anti-dengue NS1 serum antibodies confirmed
      a positive DENV titer 8 years postvaccination. Based on the history and clinical
      findings, a primary differential diagnosis for this chronic, cyclic platelet
      pathology was autoimmune platelet destruction with potential bone marrow
      involvement.

PMID- 28518479
TI  - SU-E-T-500: Pencil-Beam versus Monte Carlo Based Dose Calculation for Proton
      Therapy Patients with Complex Geometries. Clinical Use of the TOPAS Monte Carlo
      System.
AB  - PURPOSE: To investigate the necessity of the verification of dose distributions
      using Monte Carlo (MC) simulations for proton therapy of head and neck patients
      and other complex patient geometries. METHODS: TOPAS, a TOol for PArticle
      Simulations that makes MC simulations easy-to-use for research and clinical use
      and is layered on top of Geant4, has been used to simulate the treatments of head
      and neck patients at the Massachusetts General Hospital (MGH). The resulting dose
      distributions have been compared to pencil beam calculations based on the XiO
      treatment planning system. Dose difference distributions were used to highlight
      areas where the two algorithms did not agree. Dose volume histograms are utilized
      to investigate the overall agreement of the planned doses in target structures.
      RESULTS: 21 head and neck patients, both nasopharynx and spinal cord, were
      investigated. The field complexity ranges from a single field up to 13 fields.
      For all patients, the dose in the clinical target volume agrees well.
      Nevertheless, differences in critical structures around the targets have been
      observed mostly due to range differences between the two algorithms. CONCLUSIONS:
      Pencil beam algorithms provide an accurate description of dose in the target
      volume. However, we conclude that the differences between MC simulations and
      pencil beam algorithms in regions outside the target for complex geometries, such
      as present in head and neck patients, support the necessity of routine use of MC
      simulations for treatment verifications before treatment. TOPAS is aiming to make
      such routine simulations available to all researchers and clinics. An automated
      interface utilizing TOPAS to enable such simulations has been developed at MGH
      and should become routinely used in the near future for patients with complex
      geometries. NIH/NCI R01 CA140735.

PMID- 28518478
TI  - Robotic lower anterior resection for a regrowth following complete clinical
      response - a video vignette.

PMID- 28518481
TI  - SU-E-T-532: Comparison of Dose Distributions Calculated Using Different Planning
      Systems with Radiochromic Film Measurements in an Inhomogeneous Phantom.
AB  - PURPOSE: Accurate modeling of the dose distribution in a lung tumor is
      challenging for traditional dose calculation algorithms. We compare the dose
      distributions of four commercial dose calculation Methods: Raysearch (Raysearch
      Laboratories) and Pinnacle (Philips Healthcare) collapsed cone, and Eclipse AAA
      and Eclipse Acuros,(Varian Medical Systems) with measurements using radiochromic
      film in a lung tumor phantomMethods: A simple lung tumor phantom was constructed
      using a thermoplastic cylinder 29 mm diameter and 40mm in length (density 1.3
      gm/cc) imbedded in cork phantom 25 * 25 * 20 cm of density 0.32 gm/cc. Nine film
      layers normal to the axis of the cylinder where placed between layers of cork,
      above, below and through the cylindrical inhomogeneity. The phantom was
      irradiated with a single asymmetric 10*10 cm 6 MV field with the central axis
      collinear with the cylinder axis. Thirteen film exposures at 5 cm depth taken
      with doses 0-10 Gy were used to calibrate the film. The phantom was CT scanned
      and the DICOM study loaded into each of the treatment planning systems to
      calculate the dose distribution in the phantom. RESULTS: Away from cork-poly
      interfaces, agreement between the four algorithms was within 3% of the film
      measurements. For Acuros, the dose at the edge of the cylinder was found to be up
      to 2% lower than that at the center of the cylinder possibly because of the loss
      of lateral electron equilibrium. CONCLUSIONS: All four algorithms achieved
      remarkable agreement with the radiochromic film measurement. The Acuros algorithm
      appeared to more accurately model the peripheral dose deficit in the tumor,
      although a more detailed study is required for confirmation.

PMID- 28518480
TI  - SU-E-T-521: Dosimetric Effect on Variation of Patient Size in Prostate Volumetric
      Modulated Arc Therapy.
AB  - PURPOSE: To evaluate dosimetric variations of planning target volume (PTV) on
      critical organs such as rectal wall, bladder and femoral head, when the patient
      size changes due to weight loss in prostate volumetric modulated arc therapy
      (VMAT). METHODS: Three patients with small (32.0 cm3 ), medium (48.4 cm3 ) and
      large (86.5 cm3 ) prostate, selected from a group of 30 were planned for prostate
      VMAT using the 6 MV photon beam. Patient size reduction due to weight loss was
      modeled by contracting the external body contour with reduced depths (0.5 - 2 cm)
      in the anterior and both lateral directions. Original normal tissue excluded from
      the contracted body contour was replaced by air. Dose calculation was repeated
      with the same planned beam geometry and dose prescription. Dose-volume
      histograms, dose-volume points of the PTV, clinical target volume (CTV) and
      critical organs were calculated with variations of reduced depth. RESULTS: D99%
      of the PTV and CTV were found to have increased 2.65 +/- 0.03% per cm and 2.75 +/
      0.15% per cm of reduced depth in the range of 0.5 and 2 cm. D30% of the rectal
      wall and bladder increased 2.29 +/- 0.12% per cm and 2.31 +/- 0.83% per cm,
      respectively. D5% of the femoral head increased by 3.30 +/- 0.11% per cm of
      reduced depth. Moreover, there was more than 5% increase of minimum, maximum and
      means doses for the PTV, CTV and critical organs when the reduced depth reached 2
      cm. CONCLUSIONS: This study provided estimated results of dosimetric changes due
      to variation of patient size in prostate VMAT. The dosimetric information should
      help radiation oncology staff to justify changes of dose distribution, when
      patient weight loss occurs during prostate VMAT. Dose variations of more than 5%
      were found when the patient's reduced depth was equal to 2 cm. Actual or
      potential conflicts of interest do not exist.

PMID- 28518482
TI  - SU-E-T-543: Beam Attenuation Characteristics of Treatment Couches.
AB  - PURPOSE: Measure photon beam attenuation characteristics of the Varian EXACT,
      Varian IGRT treatment couches and two CIVCO Universal extensions; and assess
      accuracy of Varian's Eclipse treatment planning system in modeling the beam
      attenuation of each couch. METHODS: Dose Measurements were taken using a Farmer
      ion chamber inside a cylindrical acrylic phantom. They were taken for two photon
      energies (6MV and 15MV), at three different field sizes, for various gantry
      angles through the couch. EXACT couch was tested both with the adjustable rails
      pushed to the outside of the couch, and pushed to the center of the couch. IGRT
      couch was divided by thickness into three sections. Effects on surface dose were
      measured using a Tissue Maximum Ratio or Percent Depth Dose curve. CIVCO
      extensions were CT scanned for inclusion in the planning system. All measurements
      were modeled in the Eclipse treatment planning system for comparison. RESULTS:
      Maximum attenuation was measured at 6MV with the smallest field for all couch
      setups. The EXACT couch produced a maximum attenuation of 19.2% and a surface
      dose increase of 47% of Dmax through the couch. Maximum attenuation for the IGRT
      couch and both CIVCO extensions were between 6-8%. Through the couch, the IGRT
      couch showed a surface dose increase of 29% of Dmax,; the CIVCO extensions
      produced a surface dose increase of 33% and 7% of Dmax. Maximum difference
      between measured and planned dose was 7%, for the EXACT couch, 1.9% for the IGRT
      couch and 2.4% for both CIVCO extensions. CONCLUSIONS: These treatment couches
      were shown to affect delivered and surface dose. Including the couch structure
      during treatment planning can account for the couch attenuation in most cases,
      but some attenuation values are underestimated in the planning software. Largest
      effects are for oblique treatment angles using low energy and small field sizes.

PMID- 28518483
TI  - SU-E-T-514: Implementation and Commissioning of a Micro Multileaf Collimator in
      Pinnacle Treatment Planning System.
AB  - PURPOSE: To model and validate, in a Pinnacle treatment planning system, a
      Brainlab micromultileaf collimator mounted on a Primus Siemens accelerator. The
      objective is to take advantage of the collapsed cone convolution algorithm and
      the ability of this system modelling rounded leaf- end MLC's. METHOD: The micro
      multileaf collimator was modelled using fixed accelerator jaws with a value of
      9.2*9.2 cm2 . Profiles and depth dose curves for a wide range of square fields at
      SSD of 100 cm and depths of 1.5,5,10 and 20 cm were measured using a Scanditronix
      stereotactic SFD diode. Output factors were measured using a stereotactic
      unshielded diode for field sizes from 0.6*0.6 cm2 to 3*3 cm2 . For wider fields a
      Scanditronix ic15 ionization chamber was used. EDR2 films were used to measure
      adjacent fields in the transverse and longitudinal direction. The film
      measurements were compared to Pinnacle calculations to model and validate the
      leaf tip radius, leaf offset calibration values and tongue and groove width.
      RESULTS: Pinnacle calculations and measurements agree within 2% or 2mm except for
      the tails of largest fields where differences are <3.5%. Comparison of film
      measurements and Pinnacle calculations give the optimal value for leaf tip radius
      of 15 cm and for tongue and groove width of 0.04 cm. CONCLUSIONS: Pinnacle models
      a Brainlab micromultileaf collimator mounted on a Siemens Primus accelerator with
      acceptable results for clinical treatments.

PMID- 28518477
TI  - Acute oligodendrocyte loss with persistent white matter injury in a third
      trimester equivalent mouse model of fetal alcohol spectrum disorder.
AB  - Alcohol exposure during central nervous system (CNS) development can lead to
      fetal alcohol spectrum disorder (FASD). Human imaging studies have revealed
      significant white matter (WM) abnormalities linked to cognitive impairment in
      children with FASD; however, the underlying mechanisms remain unknown. Here, we
      evaluated both the acute and long-term impacts of alcohol exposure on
      oligodendrocyte number and WM integrity in a third trimester-equivalent mouse
      model of FASD, in which mouse pups were exposed to alcohol during the first 2
      weeks of postnatal development. Our results demonstrate a 58% decrease in the
      number of mature oligodendrocytes (OLs) and a 75% decrease in the number of
      proliferating oligodendrocyte progenitor cells (OPCs) within the corpus callosum
      of alcohol-exposed mice at postnatal day 16 (P16). Interestingly, neither mature
      OLs nor OPCs derived from the postnatal subventricular zone (SVZ) were
      numerically affected by alcohol exposure, indicating heterogeneity in
      susceptibility based on OL ontogenetic origin. Although mature OL and
      proliferating OPC numbers recovered by postnatal day 50 (P50), abnormalities in
      myelin protein expression and microstructure within the corpus callosum of
      alcohol-exposed subjects persisted, as assessed by western immunoblotting of
      myelin basic protein (MBP; decreased expression) and MRI diffusion tensor imaging
      (DTI; decreased fractional anisotropy). These results indicate that third
      trimester-equivalent alcohol exposure leads to an acute, albeit recoverable,
      decrease in OL lineage cell numbers, accompanied by enduring WM injury.
      Additionally, our finding of heterogeneity in alcohol susceptibility based on the
      developmental origin of OLs may have therapeutic implications in FASD and other
      disorders of WM development.

PMID- 28518484
TI  - SU-E-T-554: PTV to Skin Proximity for Head and Neck IMRT Treatment Planning.
AB  - PURPOSE: The goal of this work was to evaluate measured vs. calculated surface
      dose as a function of PTV-to-skin proximity and calculation matrix oxel size,
      determine effects on plan quality, and provide parameters and levels of
      uncertainty for clinical use. METHODS: A right-sided CTV with the lateral border
      5mm from the surface was delineated on the CT data of a head and neck phantom. A
      5mm PTV was generated except laterally where distances of 0-5mm were used. A 7
      field IMRT plan was generated using the Eclipse TPS. Optimization was performed
      where 95% of the PTV receives the prescription dose using a matrix size of 2mm3 .
      Dose calculations were repeated for grid sizes of 1, 3 and 5mm3 . For each plan
      nine point dose values were obtained just inside the phantom surface,
      corresponding to a 2cm2 grid near the central target region. Nine ultra-thin TLDs
      were placed on the phantom surface corresponding to the grid. Measured and
      calculated dose values were compared. Conformality, homogeneity and target
      coverage were compared. RESULTS: Surface dose is over-estimated by the TPS by 21
      and 8% for 5 and 3mm3 voxels, respectively and accurately predicted for 2mm3
      voxels. A voxel size of 1mm3 results in underestimation of 13%. Conformality
      improves with increasing PTV to skin distance and a CI of unity results for grid
      sizes of 1-3mm3 between 4 and 4.5mm. Hot spot decreases as the PTV moves away
      from the surface and falls below 110% at 4mm. Underdosage worsens as the PTV
      approaches the skin. CONCLUSIONS: For decreasing PTV-to-skin distance with this
      TPS, isodose conformality decreases, 'hot spot' increases, and target coverage
      degrades. Surface dose is accurately predicted for a 2mm3 voxel size, while
      choosing a finer or coarser grid results in underestimation or overestimation,
      respectively. All of the above appear to hold for VMAT.

PMID- 28518485
TI  - SU-E-T-525: Dosimetric Validation of the Algorithm Based on Linear Boltzmann
      Transport Equations for Photon 4MV Dose Calculation.
AB  - PURPOSE: To evaluate a dosimetric accuracy of AcurosXB dose calculation algorithm
      for 4 MV photon beam. METHODS: Four MV beam (Clinac-6EX) and AAA and AcurosXB
      algorithms (pre-release version 11.0.03.) were used in this study. The
      differences of the calculation with AAA (EAAA) and AcurosXB (EAXB) to the
      measurement were evaluated in the depth doses to 25 cm depth and dose profiles
      within the water and slab phantoms (water, lung and bone equivalent). In
      addition, the clinical cases, including three whole breast plans and three head
      and neck IMRT plans, were evaluated. First the AAA plans were calculated, then
      AcurosXB plans were recalculated with dose-to-medium with identical beam setup
      and monitor units as in the AAA plan. RESULTS: In the water phantom study, the
      EAAA and EAXB were up to 2.2% and 1.5% in the depth doses for the open field
      (field size = 4 - 40cm square), respectively. Under the heterogeneity conditions,
      the EAAA and EAXB were less than 4.4% and 2.2% in lung region, and less than
      12.5% and 6.3% in bone region, respectively. In the re-buildup region after
      passing through the lung phantom, the AAA overestimated the doses about 10%;
      however AcurosXB had good agreement with measurement within 3%. Dose profiles
      with AcurosXB were better agreement with measurement than AAA. In the clinical
      cases, the dose of the skin surface region with AcurosXB were higher than AAA by
      at least 10%, and the dose differences over 5% appeared in heterogeneous region.
      However, DVH shapes of each organ were similar between AAA and AcurosXB within
      2%. CONCLUSIONS: In phantom study, AcurosXB had better agreement to measurement
      than AAA, especially in heterogeneous region and re-buildup region. In the
      clinical cases, there were large differences between AcurosXB and AAA in the
      surface region. Evaluation Agreement of non-clinical versions of Acuros XB
      witha??Varian Medical Systems.

PMID- 28518486
TI  - SU-E-T-536: Is BJR Supplement #25 Recommendation for Megavoltage Energy
      Independent Scatter Factor Still Valid for Flattening Filter Free Photon Beams?
AB  - PURPOSE: In the process of measuring and validating fundamental dosimetry data
      prior to the clinical use of a treatment unit, it is prudent to compare
      measurements with previously published equivalent data. During the commissioning
      of an accelerator with flattening filter free (FFF) photon beams (Varian True
      Beam 6 MV FFF and 10 MV FFF) we compared measured Phantom Scatter Factors (Sp)
      with the Normalized Peak Scatter Factors (NPSFs) from the British Journal of
      Radiology Supplement 25 (BJR #25). The purpose of this work was to determine
      whether the energy independent NPSFs BJR#25 are valid for comparison with FFF
      photon beams. METHODS: All measurements were performed using a Varian TrueBeam
      linear accelerator with photon energies of 6-MV, 6-MV FFF and 10-MV FFF modes.
      For all measurements, a Scanditronix CC04 ionization chamber was used. Both water
      and in-air measurements were made to obtain NPSFs normalized to the 10 * 10 cm2
      field size. For measurements in water, the chamber was positioned at 100 cm
      source-to-axis distance at the depth of dose maximum. For in-air measurements,
      the chamber was positioned at 100 cm source-to-axis distance with appropriate
      build-up cap. From BJR #25, NPSFs were obtained for comparison with the
      measurements. RESULTS: The NPSF agreement between the 6-MV and 6-MV FFF with the
      BJR#25 were all within +/-0.5%. The agreement ranged from 0.996 to 1.004 and
      0.995 to 1.002 for 6-MV and 6-MV FFF, respectively. We also found that 10-MV FFF
      showed very similar trend. CONCLUSIONS: The scatter factors reported in BJR #25
      are valid for comparison for 6-MV, 6-MV FFF, and 10-MV. Additional investigation
      is needed to further understand the dosimetric characteristics of FFF mode.

PMID- 28518487
TI  - SU-E-T-502: Dose Perturbation Effects Near Implant Surfaces Caused by Secondary
      Electron Transport in Photon-Beam Therapy.
AB  - PURPOSE: To investigate the dose perturbation effects at interfaces between water
      and a Titanium implant, attributable to secondary electron transport across the
      interface, during high energy photon radiotherapy. While dose enhancement is
      characteristic for the proximal interface of a high-atomic number implant, the
      dose perturbation at the distal interface varies from reduction to enhancement,
      requiring proper computation of secondary electron transport effects. The
      backward and forward perturbation factors pb and pf will be calculated. METHODS:
      Using DOSRZnrc, depth dose curves were computed in a water phantom using photon
      spectra of nominal energies 4, 6, 10, 15, 24 MV for conditions (i) homogeneous
      water without any insert, (ii) alternatively with Titanium inserts of thicknesses
      3 and 5 cm placed at 10 cm water depth. Backscatter factor pb was computed as the
      ratio of the dose with implant against that without implant, whereas pf was
      calculated by first accounting for photon attenuation in the implant and then
      taking the ratio of the dose with implant against that without implant. RESULTS:
      At the front interface, pb is independent of the material thickness and varies
      slightly with beam energy and incident angle. On consideration of photon
      attenuation in the implant, pf was also found to be independent on material
      thickness, but strongly varying with energy, including change of sign.
      CONCLUSIONS: For 4-24 MV photon beams the maximum spread of the dose perturbation
      effect remains within only a few millimeters from the interface, with pb values
      ranging from 1.18-1.22, while factor pf ranges from 0.9-1.21 at normal incidence,
      indicating the extent to which planning systems may over- or underestimate the
      doses near implant interfaces. At inclined beam incidence the dose perturbation
      effects even increase, and for instance pb (1.24-1.25) and pf (0.85-1.32) were
      determined for 6 MV and 24 MV beams at 45 degrees  incidence.

PMID- 28518488
TI  - SU-E-T-547: Rotating Shield Brachytherapy (RSBT) for Cervical Cancer.
AB  - PURPOSE: To assess rotating shield brachytherapy (RSBT) delivered with the
      electronic brachytherapy (eBT) source comparing to intracavitary (IC) and
      intracavitary plus supplemental interstitial brachytherapy (IC+IS BT) delivered
      with conventional isotope radiation source. METHOD AND MATERIALS: IC, IC+IS and
      RSBT plan was simulated for 5 patients with advanced cervical cancer (>40cc). One
      BT plan for each patient (fraction 1) guided by magnetic resonance imaging (MRI)
      was used in our treatment planning system (TPS). A bio- and MRI-compatible
      polycarbonate (Makrolon Rx3158) intrauterine applicator was simulated for IC and
      RSBT, and the vienna applicator was simulated for IC+IS BT. 192Ir was used as the
      radiation source of IC and IC+IS BT; Xoft AxxentTM eBT source was used for RSBT.
      A 0.5 mm thick tungsten shield was used for RS-BT with different azimuthal and
      zenith angles. The total dose for each plan was escalated as the external beam
      radiation therapy (EBRT) plus BT times fraction number (5 in our case). RESULTS:
      RSBT and IC+IS BT had higher dose conformity in terms of D90 than IC BT for all
      the patients. The advantage of RSBT over IC+IS BT was dependent on the shield
      emission angle, tumor shape and tandem applicator location. The delivery time of
      RSBT was increased as finer emission angle was selected. CONCLUSIONS: RSBT is a
      less-invasive potential alternative to conventional IC and IC+IS BT for treating
      bulky (>40cc) cervical cancer. RSBT can provide better treatment outcome with
      clinically acceptable increased delivery time if proper emission angle is
      selected based on the tumor shape and tandem applicator location. supported in
      part by NSF grants CCF-0830402 and CCF-0844765; and the NIH grant K25-CA123112,
      and American Cancer Society seed grant (IRG-77-004-31).

PMID- 28518489
TI  - SU-E-T-518: Dose Perturbation at Air-Tissue Interface in Proton Beam Therapy.
AB  - PURPOSE: The loss of transverse equilibrium along the central axis of the proton
      beam in the presence of the air/tissue interface creates dose perturbation that
      has not been fully quantified. This gets magnified in small fields that are used
      for lung and patch up fields. Air-tissue dose perturbation is studied in a
      phantom and verified with Monte Carlo simulation. METHODS: Air channel of
      variable thickness that could be found in trachea, larynx and small lesions in
      lung were studied. To mimic air/tissue interface a simple phantom geometry was
      used with EBT films. The results confirmed the presence of dose perturbations
      which were investigating using water phantom in reference condition (10*10 cm2
      field, 16 cm range and 10 cm SOBP). A variable air column was created in the
      front of the phantom. A small volume ion chamber was used to collect high
      resolution profile data in water. The simulation was performed with 3*107
      particles with the Monte Carlo particle transport code FLUKA version 2011.2.10
      with cut off energy of 100keV. RESULTS: The dose perturbations were visible on
      film and quantified by ion chamber measurements in water. Dose perturbations at
      air-tissue interfaces are shown to be significant (-20 to +30%). The measured
      profiles show significant discontinuities in dose up to +30% in low density
      medium. The magnitude is dependence on the location and width of the air gap.
      Under and over dose perturbation pattern is not predicted by treatment planning
      system (TPS) due to proton transport algorithm and calculation bin. The Monte
      Carlo simulation confirmed our measured data. CONCLUSIONS: Significant dose
      perturbation exists with high-dose region in low density medium that is not
      predicated by TPS. The magnitude and shape is position and gap size dependent.
      This study provides the presence of dosimetric discontinuities that should be
      evaluated clinically at interfaces.

PMID- 28518490
TI  - SU-E-T-558: Assessing the Effect of Inter-Fractional Motion in Esophageal Sparing
      Plans.
AB  - PURPOSE: To compare esophageal dose distributions in esophageal sparing IMRT
      plans with predicted dose distributions which include the effect of inter
      fraction motion. METHODS: Seven lung cancer patients were used, each with a
      standard and an esophageal sparing plan (74Gy, 2Gy fractions). The average max
      dose to esophagus was 8351cGy and 7758cGy for the standard and sparing plans,
      respectively. The average length of esophagus for which the total circumference
      was treated above 60Gy (LETT60) was 9.4cm in the standard plans and 5.8cm in the
      sparing plans. In order to simulate inter-fractional motion, a three-dimensional
      rigid shift was applied to the calculated dose field. A simulated course of
      treatment consisted of a single systematic shift applied throughout the treatment
      as well a random shift for each of the 37 fractions. Both systematic and random
      shifts were generated from Gaussian distributions of 3mm and 5mm standard
      deviation. Each treatment course was simulated 1000 times to obtain an expected
      distribution of the delivered dose. RESULTS: Simulated treatment dose received by
      the esophagus was less than dose seen in the treatment plan. The average
      reduction in maximum esophageal dose for the standard plans was 234cGy and 386cGY
      for the 3mm and 5mm Gaussian distributions, respectively. The average reduction
      in LETT60 was 0.6cm and 1.7cm, for the 3mm and 5mm distributions respectively.
      For the esophageal sparing plans, the average reduction in maximum esophageal
      dose was 94cGy and 202cGy for 3mm and 5mm Gaussian distributions, respectively.
      The average change in LETT60 for the esophageal sparing plans was smaller, at
      0.1cm (increase) and 0.6cm (reduction), for the 3mm and 5mm distributions,
      respectively. CONCLUSIONS: Interfraction motion consistently reduced the maximum
      doses to the esophagus for both standard and esophageal sparing plans.

PMID- 28518491
TI  - SU-E-T-529: Dosimetric Evaluation with Heterogeneity in Acuros XB Advanced Dose
      Calculation Algorithm and Anisotropic Analytical Algorithm (AAA).
AB  - PURPOSE: To evaluate accuracy of Acuros XB Advanced Dose Calculation Algorithm
      and Anisotropic Analytical Algorithm (AAA) with measurements in predicting doses
      beyond air gaps. METHODS AND MATERIALS: Three virtual phantoms with layers were
      created in Eclipse Treatment Planning System. Each layer in phantoms was assigned
      in terms of water (top), air (middle) and water (bottom) medium. Central axis
      depth dose in water (bottom medium) beyond 2, 4 and 6 cm air gaps were computed
      for 5 cm water equivalent material positioned before air gaps. Dose computation
      was performed for 6MV photon beam with 3*3 and 5*5 cm2 field sizes at 100 cm SSD
      to surface of phantoms using AAA_10.0.28 and Acuros XB_10.0.28. Next, solid water
      and Styrofoam were manufactured to mimic virtual phantoms. By keeping identical
      field, beam parameters, and geometries that were used for dose computation, 100
      MUs were delivered to phantoms, and measurements at selected depths were acquired
      with cylindrical ionization chamber. Measured central axis depth doses were
      compared against calculated central axis depth doses computed from Acuros XB and
      AAA. RESULTS: Acuros XB predicted doses within +/-2% of measured doses except at
      1cm depth in phantoms with 4 cm air gap (-2.4%) and 6 cm air gap (-2.8%) for
      field size 3*3cm2 . Acuros XB showed better dose prediction compared to AAA at
      all measured depths. Smallest test field size in phantom with largest air gap
      produced highest range (between depths 1 and 5 cm) in percentage dose difference
      (AAA: -2.9% to -9.9% and Acuros XB: -2.8% to 1.5%). Improper modeling of primary
      beam attenuation or lateral scatter (or combination of both) within air gap may
      have resulted into dose discrepancies. CONCLUSIONS: The findings suggest Acuros
      XB is more accurate to use in dose predictions when tumor is located beyond small
      air cavity (heterogeneity) within the patient.

PMID- 28518492
TI  - SU-E-T-540: Evaluation of Forced-Density Corrected Dose Calculation for Lung
      Cancer Treatment.
AB  - PURPOSE: The study was aimed to evaluate the accuracy of lung cancer treatment
      dose calculations using a bulk electron density for forced-density correction, in
      situations where CT images are acquired in other institutions and the information
      of CT number to electron density (CT-to-ED) conversion is unavailable for
      conducting pixel density correction. METHODS: Eleven 3D SBRT lung cases were
      studied. Treatment plans were generated initially with pixel-density correction
      using a known CT-to-ED conversion, in a CMS XIO treatment planning system using
      superposition algorithm. The plans were re-calculated with contour-based density
      correction, i.e., forced-density correction: a density of 0.26 g/cm3 was assigned
      to lung structures, which was a population average taken from a literature, and
      unit density was assigned to other structures. Monitor units were kept the same
      in both plans. RESULTS: The doses calculated using forced-density correction were
      compared against those calculated using pixel-density correction. The absolute
      percentage differences of PTV D95, PTV mean dose, and V20, among the 11 cases,
      were 2.49+/-1.69%, 1.69+/-1.5%, and 1.88+/-2.36%, respectively. CONCLUSIONS: The
      results showed that the dose calculation using the bulk density and forced
      density correction generated dose distributions close to those calculated using
      pixel-density correction and actual CT-to-ED conversion. None.

PMID- 28518493
TI  - SU-E-T-506: Dosimetric Study for Shallow-Seated Tumor Using Passive/active
      Scanning Proton Beam.
AB  - PURPOSE: To investigate the possibility of using a single spot scanning proton
      beam to treat superficial lesions. METHODS: A cylindrical phantom with a
      simulated superficial target (it seated 0.5-4cm depth from the surface, volume:
      270cm3 ) was created in Eclipse treatment planning system. Three proton plans
      were generated: (a) a single AP uniform scanning beam with aperture and range
      compensator; (b) a single AP spot scanning beam with a pre-absorber. The location
      and thickness of the pre-absorber were calculated using Geant4 to Monte Carlo
      code to make use of the available spot scanning beams to get a conformal plan.
      (c) a five-beam spot scanning beam plan using multi-field optimization. The
      prescription is 54 cobalt grey equivalent (CGE) which covers 95% of the target.
      The target coverage, lateral penumbra at 2 and 4cm depth in water, the doses to
      normal tissue (phantom-target) and skin (2mm from the surface) were evaluated and
      compared for three plans. RESULTS: The mean doses to the target are comparable
      within 2.4% for all three plans. The conformity indices (at 95%) are 1.36, 1.04
      and 0.98 for plan (a), (b) and (c) respectively. The lateral penumbra (80% to
      20%) for plan (a), (b) are both 0.73 cm, while it is 3.75 cm for plan (c). The
      skin dose which received more than 40 (CGE) from plan (a) is 10% higher than that
      of other two plans. Plan (c) has 70% higher mean doses to normal tissue than that
      of plan (a) and (b). CONCLUSIONS: Each plan provides good coverage of target. And
      in this study, it showed that, with a properly designed pre-absorber, it is
      possible to use a single spot scanning beam to treat superficial lesion. The plan
      provides good target coverage and maintains normal tissue sparing in the mean
      time.

PMID- 28518494
TI  - SU-E-T-510: Calculation of High Resolution and Material-Specific Photon Energy
      Deposition Kernels.
AB  - PURPOSE: To calculate photon energy deposition kernels (EDKs) used for
      convolution/superposition dose calculation at a higher resolution than the
      original Mackie et al. 1988 kernels and to calculate material-specific kernels
      that describe how energy is transported and deposited by secondary particles when
      the incident photon interacts in a material other than water. METHODS: The high
      resolution EDKs for various incident photon energies were generated using the
      EGSnrc user-code EDKnrc, which forces incident photons to interact at the center
      of a 60 cm radius sphere of water. The simulation geometry is essentially the
      same as the original Mackie calculation but with a greater number of scoring
      voxels (48 radial, 144 angular bins). For the material-specific EDKs, incident
      photons were forced to interact at the center of a 1 mm radius sphere of material
      (lung, cortical bone, silver, or titanium) surrounded by a 60 cm radius water
      sphere, using the original scoring voxel geometry implemented by Mackie et al.
      1988 (24 radial, 48 angular bins). RESULTS: Our Monte Carlo-calculated high
      resolution EDKs showed excellent agreement with the Mackie kernels, with our
      kernels providing more information about energy deposition close to the
      interaction site. Furthermore, our EDKs resulted in smoother dose deposition
      functions due to the finer resolution and greater number of simulation histories.
      The material-specific EDK results show that the angular distribution of energy
      deposition is different for incident photons interacting in different materials.
      Calculated from the angular dose distribution for 300 keV incident photons, the
      expected polar angle for dose deposition (<thgr;>) is 28.6 degrees  for water,
      33.3 degrees  for lung, 36.0 degrees  for cortical bone, 44.6 degrees  for
      titanium, and 58.1 degrees  for silver, showing a dependence on the material in
      which the primary photon interacts. CONCLUSIONS: These high resolution and
      material-specific EDKs have implications for convolution/superposition dose
      calculations in heterogeneous patient geometries, especially at material
      interfaces.

PMID- 28518495
TI  - SU-E-T-531: Verification of Acuros Dose Calculation Accuracy in Lung SBRT.
AB  - PURPOSE: The AcurosXB Advanced Dose algorithm (Varian Medical Systems) was
      reported to give more accurate dose calculation in heterogeneous medium compared
      with the AAA algorithm. In this work, a validation of AcurosXB dose calculation
      accuracy is performed for use in lung SBRT. METHODS: A CIRS (Computerized Imaging
      Reference Systems, Inc.) lung phantom was used with a tissue equivalent 2cm
      circular target inserted into the lung. The phantom was customized to hold a
      Gafchromic EBT2 film through the center of the target. The phantom was CT
      scanned, and single field (3cm by 3cm anterior/lateral) plans, as well as VMAT
      plans were created for 6 and 10 MV energies with different delivery modalities
      (with/without a flattening filter). All plans delivered 500 cGy to the PTV which
      was the target plus 0.5 cm uniform margin. Plans were delivered on a Varian
      TrueBeamTM STx using image guidance to locate the isocenter. The film dose was
      compared with Eclipse v10.0 dose calculated with AAA and Acuros algorithms using
      FilmQA software (3cognition). Monte Carlo simulations (BEAMnrc/DOSXYZnrc) were
      performed to further validate AcurosXB calculations. RESULTS: Within the GTV, AAA
      and Acuros algorithms were in good agreement with the film measurements to within
      2% mean dose difference. AAA calculation consistently overestimated the dose to
      the lung surrounding the GTV by 5-9% for the 10MV beam and 2-4% for the 6MV beam.
      Acuros and MC calculations were found to be in good agreement with EBT2 film
      measurement within 2% at 6MV including the build up and build down regions.
      CONCLUSIONS: The CIRS customized lung phantom with EBT2 films was found to be an
      excellent tool in validating the dose calculation algorithm for lung SBRT
      application. AcurosXB was found to be more accurate than AAA algorithm in lung
      and near lung/tissue interfaces.

PMID- 28518496
TI  - SU-E-T-542: Impact of Tongue-And-Groove Width on MLC-Defined Small Field
      Dosimetry for Pinnacle 9.0.
AB  - PURPOSE: the dosimetric impact of Tongue-and-Groove (TG) width on MLC-defined
      small fields of 1cm in X/Y-jaw directions for Pinnacle Version 9.0. METHODS: Open
      field of 5cmx5cm was created using the Physics Tool of Pinnacle Version 9.0 and
      then the MLC leaves were placed manually for creating MLC-defined small fields of
      1cmx2cm to 1cmx5cm as well as of 2cmx1cm to 5cmx1cm at the source-to-surface
      distance of 95cm and depth of 5cm. With the commissioned machine data of Varian
      6EX, a series of test machines were simulated by changing the size of MLC TG
      width (no TG gap, 0.1mm, 0.25mm, 0.5mm, 0.75mm, 1.25mm, and 1.5mm). The other
      machine/MLC parameters were set to the commissioned values of Varian 6EX. In
      addition, dose grid sizes of 2mm and 4mm were used for dose calculation purpose.
      Mapcheck measurements were performed for the MLC-defined fields of 2*1 cm to 5*1
      cm to compare with the calculated dose of Pinnacle Version 9.0. RESULTS:
      Regardless of MLC-defined small fields with X-direction size of 1cm, there was
      negligible variation of calculated dose as TG width varied from zero TG to 1.5mm.
      The calculated dose was very sensitive to the dose grid size and there was a good
      agreement of less than 3% in between measurement and calculation with the dose
      grid size of 2mm. However, there was over 5% discrepancy with the dose grid size
      of 4mm for the MLC-defiled small fields. For the MLC-defined small fields with Y
      direction size of 1cm, there was over 8% decrease of computed dose compared to
      those of small fields with X-direction size of 1 cm, even though the TG width was
      set to zero, which was that the effective field size of MLC 5cm*1cm was identical
      to that of MLC 1cm*5cm. With the dose grid size of 4mm, the calculated dose was
      underestimated over 10% compared to that of 2mm dose grid. CONCLUSIONS: Pinnacle
      Version 9.0 was insensitive to the variation of TG width from no TG to 1.5mm for
      MLC-defined small fields with X-direction size of 1cm. For the MLC-defined small
      fields with Y-direction size of 1cm, there was over 8% decrease of calculated
      doses compared to those of small fields with X-direction size of 1 cm, even
      though the TG width was set to zero.

PMID- 28518497
TI  - SU-E-T-513: Clinical Implementation of a GPU Accelerated Pencil Beam Dose
      Calculation Algorithm.
AB  - PURPOSE: This work reports a clinical implementation of a GPU accelerated pencil
      beam dose calculation algorithm (GPU-PB). METHODS: Model parameters were
      determined using in-house scripts written in MATLAB. Dose distributions in a
      water phantom were calculated using a Pinnacle TPS for various open field sizes.
      Lateral profiles at 2-mm incremental depths were used to calculate PB kernel
      parameters. Weighted sum of squares were used for least-squares parameter fitting
      utilizing a Levenberg-marquardt algorithm. Weightings were adjusted based on
      goodness of fitting and in accordance with field size to suppress deviations due
      to horn effects. The scale factor was fitted iteratively. The calculated doses
      for two patient cases were analyzed with a 3D gamma method (3%/3mm). RESULTS:
      Excellent agreement between Pinnacle calculation and GPU-PB calculation was
      achieved regarding PDD, profiles and output factor. For a head-neck 10-field step
      and-shoot IMRT case, gamma passing rate was over 99% and maximum absolute dose
      value is 75.6 Gy vs. 73.9 Gy, differing by 2.3%. Similar results were obtained
      for a SBRT lung case. Gamma passing rate is a function of PB kernel cut-off
      distance and beamlet resolution. It appears that if the highest accuracy is
      desired, a resolution of 10 mm or better in the direction parallel to MLC travel
      and a cutoff distance of 10 cm or better should be used. The calculation time
      increases with both cut-off distance and beamlet resolution. For example, GPU
      calculation time is 1.36 seconds for 5 cm cut-off distance, and increases to 4.84
      s for 15 cm cut-off distance. CONCLUSIONS: A GPU accelerated PB dose calculation
      algorithm has been implemented using clinical measurement data. Excellent
      agreement with Pinnacle TPS has been achieved. Beamlet size and PB cut-off
      distance should be chosen according to desired dose calculation accuracy and
      speed.

PMID- 28518498
TI  - SU-E-T-553: Dose-Mass Vs. Dose-Volume Optimization: A Phantom Study.
AB  - PURPOSE: To demonstrate the merits of mass-based optimization in comparison with
      volume-based optimization using a simple test phantom. METHODS: Dose-volume
      histogram-based (DVH-based) quadratic objective functions are converted into dose
      mass-histogram-based (DMH-based) objective functions by multiplying per-voxel
      volumes by per-voxel densities within the objective. A digital phantom with a 1.0
      g/cm3 target is constructed for irradiation with two beams: one beam path
      contains a 0.2 g/cm3 volume-of-interest (VOI0.2) while the orthogonal beam-path
      contains an equal-volume 0.8 g/cm3 VOI (VOI0.8). Monitor-units are computed to
      achieve a 100 cGy average target dose for each individual beam, and for two-beam
      DVH-based and DMH-based optimizations. RESULTS: For single-beam irradiation
      through VOI0.2, the average dose to VOI0.2 is 20.5 cGy. For single-beam
      irradiation through VOI0.8, the average dose to VOI0.8 is 25.2 cGy. Traversing
      the low density volume results in ~23% lower dose. When DVH- and DMH-based
      optimizations are performed such that target dose-volume-histograms of the
      optimizations match, for the DVH optimization 60% vs. 40% of the dose is
      delivered through VOI0.2 vs. VOI0.8. For DMH-optimization, the split between dose
      delivered through VOI0.2 vs. VOI0.8 is 70% vs. 30%. CONCLUSIONS: When density is
      constant, there is no difference between DVH- and DMH-based optimizations.
      However, in heterogeneous media, DMH and DVH solutions differ when low and high
      density materials have the same dose objectives. Delivering target dose through
      lower density VOIs facilitates target dose deposition due to a decrease in
      attenuating material, and the decreased attenuation lowers dose to the low
      density VOI. From mathematical and physical points of view dose-mass optimization
      is more general than dose-volume optimization.

PMID- 28518499
TI  - SU-E-T-524: The Effect of CT Contrast on CyberKnife Treatment Planning.
AB  - PURPOSE: To investigate the effect of CT contrast enhancement (CE) on the 3D dose
      distributions of non-coplanar small field beams in the CyberKnife (CK) treatment
      planning system. METHODS: Twenty patients treated by pre-CE CT plans were
      recruited to this retrospective plan study. Their post-CE CT plans were based on
      the pre-CE CT plan data and calculated using the same MU and beam paths in either
      Ray-Tracing or Monte Carlo (MC) algorithms. The differences in doses of the beam
      path and the reference point and in DVHs of target and OARs between the pre-CE CT
      and the post-CE CT plans were compared. The minimum dose, the maximum dose, the
      mean dose, and the dose received to 50% of the target and OARs volumes, and the
      target volume coverage were also compared. RESULTS: The dose differences between
      the pre-CE and post-CE plans in a single beam path were less than 50 cGy in both
      calculation algorithms. At the center of target volume, it was 1.9% (maximum
      6.2%) in Ray-Tracing and 1.5% (maximum 4.0%) in MC, with respect to the
      prescription dose. The post-CE plans showed on average 2% decrease in the OAR
      maximum dose (maximum 6.4% in Ray-Tracing and 5.8% in MC). Regardless of the
      algorithms, the dose to the target and the target volume coverage of post-CE
      plans were on average reduced by 2% and 1 %, respectively, with a maximum
      reduction of 6.1% (in Ray-Tracing) in the minimum target dose. CONCLUSIONS: The
      CK treatment plan using the post-CE CT could generally result in a few % dose
      differences from the pre-CE CT plan. However, it could be more than 6%, depending
      on the target positions in the body and the calculation algorithms. Thus the post
      CE CT in CK treatment plans should be used with a caution.

PMID- 28518500
TI  - SU-E-T-535: Proton Dose Calculations in Homogeneous Media.
AB  - PURPOSE: To develop a pencil beam dose calculation algorithm for scanned proton
      beams that improves modeling of scatter events. METHODS: Our pencil beam
      algorithm (PBA) was developed for calculating dose from monoenergetic, parallel
      proton beams in homogeneous media. Fermi-Eyges theory was implemented for pencil
      beam transport. Elastic and nonelastic scatter effects were each modeled as a
      Gaussian distribution, with root mean square (RMS) widths determined from
      theoretical calculations and a nonlinear fit to a Monte Carlo (MC) simulated 1mm
      * 1mm proton beam, respectively. The PBA was commissioned using MC simulations in
      a flat water phantom. Resulting PBA calculations were compared with results of
      other models reported in the literature on the basis of differences between PBA
      and MC calculations of 80-20% penumbral widths. Our model was further tested by
      comparing PBA and MC results for oblique beams (45 degree incidence) and surface
      irregularities (step heights of 1 and 4 cm) for energies of 50-250 MeV and field
      sizes of 4cm * 4cm and 10cm * 10cm. Agreement between PBA and MC distributions
      was quantified by computing the percentage of points within 2% dose difference or
      1mm distance to agreement. RESULTS: Our PBA improved agreement between calculated
      and simulated penumbral widths by an order of magnitude compared with previously
      reported values. For comparisons of oblique beams and surface irregularities,
      agreement between PBA and MC distributions was better than 99%. CONCLUSIONS: Our
      algorithm showed improved accuracy over other models reported in the literature
      in predicting the overall shape of the lateral profile through the Bragg peak.
      This improvement was achieved by incorporating nonelastic scatter events into our
      PBA. The increased modeling accuracy of our PBA, incorporated into a treatment
      planning system, may improve the reliability of treatment planning calculations
      for patient treatments. This research was supported by contract W81XWH-10-1-0005
      awarded by The U.S. Army Research Acquisition Activity, 820 Chandler Street, Fort
      Detrick, MD 21702-5014. This report does not necessarily reflect the position or
      policy of the Government, and no official endorsement should be inferred.

PMID- 28518501
TI  - SU-E-T-501: Perturbation of TG-43 Parameters of the Brachytherapy Sources under
      Insufficient Scattering Materials.
AB  - PURPOSE: According to the TG-43 recommendations of American Association of
      Physicist in Medicine (AAPM), the dosimetry parameters of brachytherapy sources
      are obtained in a water phantom with full scattering conditions. However, in many
      actual clinical treatments the source are not surrounded with sufficient tissue
      in all directions to provide the full scattering condition. HDR brachytherapy of
      the breast or 125I eye-plaque treatment of the ocular melanoma are among the
      treatment sites that fits this category. In this project, the impact of
      insufficient phantom material surrounding the 137Cs, 192Ir, and 103Pd
      brachytherapy source on their TG43 dosimetric characteristics has been
      investigated. METHODS: In this study, the effect of the insufficient tissue
      (referred here as missing tissues) around the brachytherapy sources on their TG
      43 dosimetric parameters have been investigated using MCNP5 Monte Carlo code. The
      brachytherapy sources were simulated in different locations inside a cubical
      water phantom with the dimensions of 30*30*30 cm3 . The variation of the
      dosimetric parameters of the three sources (i.e. I>, g(r), and F(r,theta)) were
      compared to the values from full scattering conditions (i.e. source at the center
      of the phantom). RESULTS: The results of this study indicate the variation of
      g(r)and 2D anisotropy function of the brachytherapy sources as a function of the
      missing tissue thickness. These changes increase by decreasing the energy of the
      photons emitted by the brachytherapy sources. These differences are mainly due to
      the lack of full scattering condition for the points near the phantom boundary.
      CONCLUSIONS: Unlike the published data for symmetric, but insufficient phantom
      material around the source, the impact of asymmetric phantom materials have been
      evaluated on dosimetric characteristics of the brachytherapy sources.

PMID- 28518502
TI  - SU-E-T-546: Cumulative Dose Evaluation for Head and Neck Cancers.
AB  - PURPOSE: In this study, we retrospectively analyzed patient treatments utilizing
      a prototype of the Varian EclipseTM treatment planning system integrated with
      their new DARTTM technology. Structure volume changes, structure displacements,
      and dose deviations were analyzed to assess the need for more adaptive treatment
      planning. METHODS: Ten patients with head and neck cancer who received daily cone
      beam imaging CTs, as part of their radiation therapy, were chosen from the
      University of California San Diego Moores Cancer Center database. With the aid of
      DARTTM, we were able to retrospectively calculate the accumulated dose to both
      the tumor and healthy tissue over the entire course of treatment. This process
      was accomplished through rigid and deformable registrations of their daily cone
      beam CT scans and cumulative dose measurements. Volumetric changes were compared
      to their original planning CT image. RESULTS: Our results showed notable changes
      to the parotid glands in all patients, in both structure shrinkage and dose
      escalation, which were often correlated with a medial displacement of the glands
      towards the high-dose region. Our study estimated that the mean rate of parotid
      volume reduction was 0.18 cm3 /treatment day with a range of 0.08 - 0.31 cm3
      /treatment day. GTV, CTV, and PTV regions also showed significant volume
      reductions which was shown to be more pronounced during the first half of
      treatment. In 6 out of 9 patients with contoured parotids, the absorbed dose
      increase to these glands was >3%. The GTV, CTV, and PTV showed smaller
      variations, and in only 1 out of the 10 patients studied did the dose
      accumulation increase >3%. CONCLUSIONS: While the program used was just a
      prototype, it is our hope for the future that this project could be integrated
      clinically to develop more adaptive treatment plans allowing for better treatment
      accuracy and patient care.

PMID- 28518503
TI  - SU-E-T-517: Characterization of Relative Doses and Source Strengths for Various
      Plaque Sizes and Tumor Dimensions in the Treatment of Uveal Melanoma.
AB  - PURPOSE: To characterize the relative doses and source strengths for various eye
      plaque sizes and tumor dimensions in the treatment of uveal melanoma. MATERIALS
      AND METHOD: Several tumors with basal diameters ranging from 6-16mm and apical
      height of 5-10mm were planned using the Pinnacle3 treatment planning system
      following the American Brachytherapy Society's recommendations. The data is based
      on 5-day implant to deliver 85Gy with a dose rate of 70.9cGy/hr. Choice of plaque
      size is based on a 2-3 mm margin on either side of the tumor. Doses to the fixed
      locations: sclera, center of the eye and opposite sclera were obtained. RESULTS:
      From our results we see larger source strengths needed for smaller plaques due to
      smaller number of sources used. The exception is with 14mm and 16mm plaques
      containing the same number of sources where the 16mm plaque has slightly higher
      source strengths. For both the inner and outer sclera, the relative dose
      increases with increasing height. For a 12mm plaque, the relative dose of the
      outer sclera increases from 4-10 times that of the Rx dose at the apex of the
      tumor. For a 20mm eye plaque, the relative dose of the outer sclera increases
      from 2-5 times that of the prescription dose at the apex of the tumor. As apical
      height increases, the relative dose at the center of the eye increases to about
      75% of the Rx dose at 10cm depth for all plaque sizes. At the inner sclera
      surface opposite the center of the tumor base the relative dose is 20-22% of the
      Rx dose for all plaque sizes. CONCLUSION: The data provided will be a helpful
      tool in evaluating and predicting complications in the retina and sclera based on
      the tumor dimensions and selected plaque size.

PMID- 28518504
TI  - SU-E-T-557: A Planning Strategy of Volumetric Modulated Arc Therapy with
      Simultaneous Integrated Boost for Intracranial Stereotactic Radiotherapy.
AB  - PURPOSE: The purpose of this planning study was to evaluate the dosimetric effect
      of dose escalation for intracranial stereotactic radiotherapy by volumetric
      modulated arc therapy (RapidArc) with simultaneous integrated boost (SIB-VMAT).
      METHODS: Dynamic conformal arc therapy (DCA), VMAT, and SIB-VMAT plans using
      Novalis Tx (Varian/BrainLAB) were performed for twenty target volumes in patients
      with intracranial metastases with median PTV of 16.0 cm3 (range 2.4-35.2 cm3 ).
      PTV was created with 2 mm expansion from GTV. All plans were generated with a
      prescribed dose of 35 Gy in 5 fractions to the PTV (D95 = 95%), and dose
      escalation up to 40 Gy (SIB-VMAT40) and 45 Gy (SIB-VMAT45) was performed only to
      the PTV-boost (PTV shrunk by 5 mm) for SIB-VMAT. Each plan was compared using
      conformity parameters. RESULTS: The average Paddick conformity index (CI) was
      0.78, 0.90, 0.91, and 0.89 for DCA, VMAT, SIB-VMAT40, and SIB-VMAT45,
      respectively. The average healthy tissue overdosage factor (HTOF), suggested by
      SALT was 0.118, 0.006, 0.007, and 0.011 for DCA, VMAT, SIB-VMAT40, and SIB
      VMAT45, respectively. The average V30, V20, and V10 of normal brain for VMAT and
      SIB-VMAT decreased by 3.0 cm3 (range 0.1-8.2 cm3 ), 3.0 cm3 (range 0.1-8.7
      cm@@@3@@), and 7.5 cm@@@3@@ (range 0.3-26.2 cm@@@3@@), respectively, compared to
      DCA depending on the target volume. CONCLUSIONS: SIB-VMAT improved dose
      conformity to the PTV for intracranial stereotactic radiotherapy, and decreased
      high and low dose volume of normal brain compared to DCA. SIB-VMAT offers the
      ability of dose escalation due to high conformity of high dose regions inside the
      target volume.

PMID- 28518505
TI  - SU-E-T-528: Appraisal of Acorus XB and Convolution Dose Algorithms in Field
      Junction of Breast Tangential/superclavicular Fields.
AB  - PURPOSE: Dose accuracy injunction regions of breast-tangential therapy is a
      challenge, and inaccurate dose predictions may lead to unreal hot/cold spots.
      Availability of the novel deterministic radiation transport method Acuros XB
      (AXB) provides a potential for more accurate dose predictions. This study
      assesses relative dose accuracies of this and the widely used other algorithms:
      collapsed cone convolution (CCC) and anisotropic analytical algorithm (AAA)
      against film measurements. METHODS: A typical tangential and superclav fileld
      combination was planned for an anthropomorphic body phantom using Pinnacle-9.0
      treatment-planning system (TPS). The created plan employing 6MV beam was
      delivered to the phantom on a Varian linac. In region of the field junction of
      tangentials & superclav, films (EBT2) were placed in coronal planes at two depths
      (~ 2 and 4 cm). Optical density was measured along and +/- 5mm away from the
      field-match line, and converted to dose using film-calibration curve specific to
      the batch of film. The same plan was also imported to Eclipse TPS using an import
      filter written in MATLAB. Algorithms Pinnacle CCC 9.0, Eclipse AAA 10.0.24 and
      AXB 11.0.3 were used for calculations. Comparison of the measured doses (assumed
      as gold standard) against doses calculated from planning-systems were preformed
      in a MATLAB platform. RESULTS: In general, dose distributions from all three TPS
      algorithms are found to agree closely with film data. Agreements between AXB and
      CCC dose calculations were found to be reasonable. AXB appears to be better in
      modeling the backscatter effects in the heterogeneous regions. AAA calculations
      gives acceptable results, but with less accuracy compared to CCC and AXB.
      CONCLUSIONS: The novel deterministic algorithm AXB in Eclipse is found to provide
      better agreement with measured data in breast-tangential therapy. Benefits of
      using Acuors XB algorithm in tangential fields planning requires further
      investigation. This work was funded by National Institutes of Health through
      grant 2R44CA105806-02 and MD Andersona?TMs Cancer Center Support Grant CA0 16672.

PMID- 28518506
TI  - SU-E-T-539: The Effect of the Scattering Volume of Phantom on Dose Calculation
      Accuracy Using Elekta's Cone-Beam Computed Tomography (CBCT) for Head-Neck
      Radiotherapy.
AB  - PURPOSE: To analyze the scattering volume effect of phantom on HU values and dose
      calculation accuracy utilizing Elekta's cone-beam computed tomography (CBCT) for
      head and neck radiotherapy. METHODS: A water phantom was designed to simulate
      different scattering volume by varying its lengthfrom 5cm to 30cm.A CIRS density
      reference phantom combined with the water phantom was used to measure the CBCT HU
      values. HU-ED correction curves for 30cm length (Correction-A) and 5cm length
      (Correction-B) were generated for CBCT dose calculation, respectively. A four
      field-box plan was designed both on CBCT and conventional CT of a head-neck
      anatomical phantom to compare the dosimetric difference. RESULTS: The maximum HU
      variance in the CBCT of the water phantom was up to 10% with varying phantom
      length. For the combined CIRS phantom, the HU value in CBCT was found to decrease
      in high-density inserts, but increase in low-density inserts with increasing
      scatter length.For dense-bone insert, the change in HU values was up to 1422HU.
      For head-neck anatomical phantom, the dose results showed an average difference
      of 0.3% of cGy /MU, 2-3mm of isodose discrepancy,and 97% of 2%/2mm DTA index for
      each beam with Correction-A; and 3.7% of cGy /MU,1.5-3cm of isodose
      discrepancy,and 59.5% of 2%/2mm DTA index for each beam with Correction-B.
      CONCLUSIONS: The scattering volume of phantom has a significant impact on the HU
      value and further HU-D calibration of Elekta's CBCT. Excellent dosimetric
      agreement between CBCT and conventional CT was found when the HU-D calibration
      phantom volume is close to patient volume imaged by CBCT.

PMID- 28518507
TI  - SU-E-T-505: BrainLab Plan Comparisons: Brain Scan Pencil Beam versus IPlan Monte
      Carlo.
AB  - PURPOSE: Monte Carlo (MC) dose modeling techniques are available in the newest
      version of Brain Lab's IPlan treatment planning system (TPS). Prior to the
      upgrade, at our facility, BrainLab's BrainScan was the treatment planning system
      available; pencil beam (PB) modeling is employed by BrainScan. As published in
      the literature, MC calculations, as compared to the PB algorithm, can generate
      differences in coverage as much as 20%. With the introduction of the new
      treatment planning system, treatment parameter comparisons were made with
      quantitative assessments. Differences due to changes in the dose calculation that
      could impact patient treatments and outcomes were investigated. METHODS: Beam
      data was collected for the new BrainLab TPS IPLAN under the conditions as
      outlined in the manufacturer's Version 1.3 data collection, commissioning and
      acceptance guidelines. Utilizing BrainLab's treatment planning systems, treatment
      plan comparisons were made. First, PB modeling treatment plans were assessed for
      each treatment plan with pencil beam modeling in the BrainScan and IPlan TPS.
      Treatment plans with MC modeling were then compared to PB models. RESULTS:
      Differences in the dose distribution, DVH values, and monitor units were
      evaluated between the older version software (BrainScan) and the newer treatment
      planning system (IPlan). As predicted by the literature, the differences in the
      MC modeling versus PB modeling were significant depending upon the anatomy (tumor
      site). Modeling comparison for the treatment plans will be presented for SRS
      (Stereotactic Radiosurgery) and Stereotactic Body Radiation Therapy (SBRT).
      CONCLUSIONS: Clinical implementation of a new treatment planning system must be
      approached with caution and with adherence to AAPM recommendations and
      guidelines. Whenever a new TPS calculation model is introduced, thorough
      comparison between former and new models should be obtained. An additional
      recommended test would be to perform an independent, end-to-end check of the
      overall system utilizing the RPC (Radiological Physics Center) phantom.

PMID- 28518508
TI  - SU-E-T-550: Influence of the Clinical Outcome and Quality of Life by Replanning
      during Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma.
AB  - PURPOSE: The purposes of this study were to expound on the benefit of replanning
      using clinical outcome and Quality of life (QoL) during Intensity-Modulated
      Radiation Therapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS: A total of
      129 new patients with NPC, who were curatively treated by IMRT from June 2007 to
      August 2011, were recruited. Eighty-six patients with repeat CT and replanning
      and 43 patients non-replanning were retrospectively analyzed. The Chinese version
      of the European Organization for Research and Treatment of Cancer Quality of Life
      (QoL) Questionnaire C30 and H&N were completed before treatment, the end of
      treatment, 1, 3, 6, 12 month after treatment. QoL and Kaplan- Meier estimators
      were used to estimate the survival function of patients with or without
      replanning. RESULTS: The clinical outcome comparison indicated that replanning
      during the IMRT for NPC improved the locoregional control (LRC) (p=0.040), but
      did not improved the overall survival (OS) (p=0.475). The 2-year LRC, OS rates
      were 92.4%, 82.2%, and 97.2%, 89.8% in non-replanning ans replanning,
      respectively. Global QoL (p=0.012) and role functioning (p=0.000) and social
      functioning (p=0.000) and dyspnea (p=0.001) and appetite loss (p=0.010) and
      constipation (p=0.010) and diarrhea (p=0.010) and speech problems (p=0.000) and
      trouble with social contact (p=0.000) and teeth (p=0.031) and opening mouth and
      dry mouth (p=0.000) and sticky saliva (p=0.015), have significantly differences
      between replanning and non-replanning in patients with NPC. CONCLUSIONS: Our
      results indicate that replanning can improve significantly LRC and QoL variables
      in patients with NPC. Grant No. 2008B198 from Zhejiang Provincial Medical and
      Health science Foundation of China.

PMID- 28518509
TI  - SU-E-T-509: Photon Spectrum Modeling of Flattening Filter Free (FFF) Beam and the
      Optimization of Model Parameters.
AB  - PURPOSE: To determine the distribution of photon spectrum on flattening filter
      free (FFF) beams, novel and fast optimization methods that were applicable on a
      convolution/superposition dose calculation algorithm were implemented. METHODS:
      Two-step optimization method was designed to model the virtual photon spectrums
      for FFF beams. At first, simple functional form of photon spectrums proposed by
      E. S. M. Ali was modified and used to make rough shapes of photon spectrum. The
      distributions of photon spectrums were defined at various field sizes (FSs) to
      consider the changes of the contribution for scattered photons. Percent depth
      doses (PDDs) at various FSs were used, and collapsed cone convolution (CCC)
      algorithm was used to calculate PDDs by considering cone-shaped photon fluence in
      fields. At next, an arbitrary functional form of photon spectrums where the
      values of photon intensity itself were free parameters was designed. Line search
      method was used for optimization and gradient terms at each free parameter were
      derived from CCC algorithm to enhance the speed of iterations. RESULTS: The mean
      energies of the optimized spectrums were decreased from 1.40 to 1.21 MeV for 6 MV
      FFF beams and from 2.45 to 1.27 MeV for 10MV FFF beams as FSs were increased from
      3*3 to 40*40 cm2 because of the contributions of scattered photons. The shape of
      the spectrums were not greatly changed with field sizes, but root mean squared
      differences (RMSDs) between the measured PDDs and the calculated PDDs using
      optimized spectrums were increased upto 0.87% as the FSs were decreased to 3*3
      cm2 . CONCLUSIONS: Developed method for spectrum modeling showed good agreements
      when the PDDs were calculated with the optimized results. Suggested method is
      proper to the radiation treatment planning systems because it only requires
      measured PDDs, and based on the analytic dose calculation algorithm. This work
      was supported by the National Research Foundation of Korea(NRFK)? grant funded by
      the Korean government (MEST)? (Grant No. K20901000001-09E0100-00110?), Varian
      Medical Systems, NCI Grant No.1R01 CA98523?, and NSF Grant No. 0854492?.

PMID- 28518510
TI  - SU-E-T-541: Dose Calculation Algorithm for External Neutron Radiotherapy Based on
      Pencil Beam Method.
AB  - PURPOSE: To evaluate the availability and performance of pencil beam algorithm
      for fast neutrons radiotherapy dose calculations and to achieve improvements in
      universality, speed and inhomogeneities corrections. METHODS: Pencil beam (PB)
      method uses integration of dose kernel cross field size to estimate dose
      distribution. In order to calculate dose kernels we used general purpose Monte
      Carlo (MC) code MCNP. The same program was used also for PB benchmarking. Multi
      group approach used for kernels calculation virtually allows calculation for
      arbitrary spectrum. Nevertheless we took four common spectra to investigate
      accuracy and to establish according corrections. Several approaches for
      inhomogeneities corrections have been investigated. The output of MC calculations
      is discrete kernel data, which does not allow fast calculations. To overcome this
      limitation we investigated different dose kernels approximations and
      integrations. RESULTS: PB dose kernel library was established. Comparison of PB
      calculation with reference algorithm shows adequate precision for arbitrary
      neutron spectra with inhomogeneities correction, while calculations are fast
      enough for optimization tasks. Secondary photon dose distributions comparison
      give worse still promising results. CONCLUSIONS: Researches of this paper show
      benefits and limitations of PB method for neutron teletherapy treatment planning.
      Calculations made during research allow saying that results of PB method are
      generally acceptable. Still additional data are needed to evaluate our results,
      probably voxel phantom MC calculations and/or beam data measurements.

PMID- 28518511
TI  - SU-E-T-512: Evaluation of Treatment Planning Dose Calculation Accuracy at the
      Interface of Prosthetic Devices.
AB  - PURPOSE: To evaluate the ability of treatment planning algorithm to accurately
      predict dose delivered at the interface of high density implanted devices.
      METHODS: A high density (7.6 g/cc) Cobalt-Chromium-Molybdenum hip prosthesis was
      molded into an epoxy-based cylindrical leg phantom. The phantom was designed to
      be separated in half to access the prosthesis and to place the TLDs. Using MVCT
      to image the apparatus, a simple treatment plan was developed using the Philips
      Pinnacle treatment planning system. Wires were placed in the molded epoxy to
      allow for accurate definition of measurement sites (TLD positions) along the
      surface of the prosthesis. Micro-cube TLDs (1 mm3 ) were placed at six
      measurement locations for which the dose had been calculated by the treatment
      planning system. An Elekta Synergy linear accelerator was used to deliver a 400
      cGy plan to the phantom with 6 MV photons in a single fraction. A total of four
      10 cm * 21 cm fields were used at 0, 90, 180, and 270 degree gantry rotations.
      RESULTS: Initial results indicate that the measured dose is 7-17% lower than the
      dose calculated by the treatment planning system. Further study using high energy
      beams are also in progress. CONCLUSIONS: Initial results indicate that the
      treatment planning system does predict the dose near a high density prosthetic
      device within 10-15% but underestimates the dose. The results of this study could
      help in designing treatment plans which would reduce the uncertainty of the dose
      delivered in the vicinity of prosthetic hip implants and similar devices.

PMID- 28518512
TI  - SU-E-T-552: Maximizing the Biological Effect of Proton Dose Delivered with
      Scanned Beam.
AB  - PURPOSE: Biological effect of radiation can be enhanced with hypofractionation,
      localized dose escalation, and controlled distribution of proton's linear energy
      transfer (LET). We evaluate potential gain in therapeutic effect from delivery of
      daily inhomogeneous fractional dose distributions in pencil beam scanning proton
      therapy (PBS-PT). METHODS: For cases of prostate cancer, we considered a
      hypofractionated course of 20 fractions of 3 Gy (assuming alpha/beta=1.5, the
      equivalent dose in 2-Gy fractions (ED2Gy) is 77.1 Gy). Two sets of dose
      distributions were planned using two opposed lateral fields to deliver a uniform
      dose: (1) in full-target plans (FTP) each beam targeted the entire gland (2) in
      split-target plans (STP), beams targeted only the respective proximal hemispheres
      (prostate split sagittally). Linear combinations of optimized beam intensity maps
      from FTP and STP, for a variety of mixing weights, were used to evaluate
      inhomogeneous fractional dose (IFD) distributions. IFD delivered doses boosting
      either hemisphere in alternating fractions, e.g., alternating between 40% and
      160% of the nominal fractional dose (1.2-4.8 Gy). The equivalent uniform dose
      (EUD) was calculated for ED2Gy distributions. IFD plans were rescaled so that the
      EUD of rectum and bladder did not increase. LET distributions were calculated
      with Monte Carlo, and compared for different plans. RESULTS: In the IFD courses,
      the whole prostate received a nearly uniform dose in every 2 fractions, however
      EUD was higher than in conventional FTP by up to 8%. Rectal EUD decreased by 2%,
      and bladder EUD was unchanged. The LET distributions of FTP and STP were
      distinctly different, thus, in IFD, LET depended strongly on the mixing weights.
      CONCLUSIONS: In PBS-PT, modestly improved therapeutic outcome can be expected
      with delivery of inhomogeneous daily dose distributions, while administering the
      prescribed dose to target over the entire course. The biological effectiveness
      may be further enhanced by optimizing the LET distributions. The project was
      supported by the Federal Share of program income earned by Massachusetts General
      Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.

PMID- 28518513
TI  - SU-E-T-523: Modeling Beam Data for Flattening Filter Free (FFF) Photon Beams.
AB  - PURPOSE: For flattening-filter free (FFF) photon beams, conventional algorithm
      based on equivalent-square to calculate dose per MU is invalid because of the non
      uniform profile. In this study, an empirical algorithm is developed to calculate
      the dose accurately, which can be used for secondary MU check for IMRT using FFF
      beams. METHODS: A kernel-based algorithm based on three parameters (a0, w0, d0)
      is used to quantify the phantom scatter characteristics of the photon beam. The
      model is modified to quantify the shape of the FFF at off-axis locations by
      fitting the primary off-axis ratio (POAR) by a linear function 1 - br, where b is
      a constant and r is the radial distance. The resulting parameters are used in a
      kernel-based dose calculation algorithm for dose calculation. RESULTS: It is
      found that the proposed model can fit the product of the fractional depth doses
      (FDD) and phantom scatter factors (Sp) for field sizes between 2 and 40 cm and
      depth between 0 and 40 cm to a max and standard deviations of 1.7% and 0.01% and
      1.8% and 0.01%, respectively, for 6 and 10 MV FFF beams. The value of b is 0.025
      and 0.0323 for 6 MV and 10 MV photons, respectively, from fitting the POAR. The
      resulting phantom scatter parameters are consistent with those obtained from MC
      simulation. If the slope is not taken into account (b = 0), then the model cannot
      fit the central-axis Sp*FDD accurately and resulted in a maximum error of 3% and
      4% for 6 and 10 MV, respectively. CONCLUSIONS: We have demonstrated that the
      shape of POAR from FFF beam will impact on the dose calculation on the central
      axis. Conventional equivalent square law concept will not be applicable for dose
      calculation for FFF beams.

PMID- 28518514
TI  - SU-E-T-534: Beam and MLC Commissioning and Assessment of Three Commercial
      Treatment Planning Systems.
AB  - PURPOSE: To assess and compare the open beam and multi-leaf collimator modeling
      of Pinnacle, Ecilpse (AAA and Acuros) and RayStation planning systems. METHOD AND
      MATERIALS: The 6MV photon beam of a Varian TrueBeam with Millennium 120 MLC was
      used for this study. Measurements made with combinations of ion chamber,
      radiochromic film, and diodes in water and plastic phantoms. Depth and crossplane
      profiles of open square fields shaped by jaws or MLC ranged from 3*3 to 40*40cm2
      and from 0 to 20 cm depth. Depth dose, flatness (80% of FWHM), and penumbra (20
      80%) of calculated and measured profiles were compared. Various MLC test patterns
      were calculated and compared with measurements to assess the modeling of the
      round leaf edge, tongue-and-groove, and interleaf transmissions. RESULTS:
      Calculated depth doses are within 1.0% and flatness is within 2% for all field
      sizes and depths. Jaw penumbrae are within 2mm and 3mm for 20*20 and 30*30cm2 at
      10cm depth respectively. MLC penumbrae (20-80%) of the three systems are within
      0.3mm and 1.0mm for a 3*3cm2 and 10*10cm2 MLC apertures. Notably, to match the
      measured MLC round-edge transmission, the half thickness (10% transmission) leaf
      tip width of the current RayStation MLC model has to be broadened to 10mm. All
      three systems appear to adequately model the tongue-and-groove. Pinnacle
      explicitly models the interleaf transmission while Eclipse and RayStation simply
      use average MLC transmission. CONCLUSIONS: All three systems are capable of
      generating clinically acceptable beam models for open fields. Based upon the
      round-edge profile, Eclipse and Pinnacle provide better MLC models than
      RayStation. Among the three systems, Eclipse took the least time and effort to
      commission these features.

PMID- 28518515
TI  - SU-E-T-545: Dose Comparison between Intravenous Contrast-Enhanced CT and Non
      Contrast CT in Treatment Planning.
AB  - PURPOSE: With increasing concern for patient dose from CT scan, we are trying to
      reduce CT scan and use intravenous contrast-enhanced CT (contrast CT) in
      treatment planning. This study is to investigate dose calculation accuracy using
      contrast CT in treatment planning for lung, esophagus and pancreas cancer.
      METHODS: We analyzed treatment plans for 8 patients for whom CT simulation was
      performed both with and without intravenous contrast agent (CA) (non-contrast
      CT). IMRT/3D plans were generated with inhomogeneity correction on the non
      contrast CT scan. Contrast CTs were fused to the non-contrast studies and all
      contours and plans were copied to the contrast CT scans. For each patient, we
      analyzed dose-volume histograms (DVH) for planning volumes (PTV) and the organs
      at-risk (OAR), comparing the doses generated on non-contrast CT scans with those
      generated on contrast CT scans. RESULTS: Maximum doses ratio Dmax(contrast)/Dmax
      (non-contrast) in PTVs was 1.0009+/-0.0013. The ratio of D05 (contrast)/D05 (non
      contrast) was 0.996+/-0.005. The ratio of mean PTV dose Dmean(contrast)/Dmean(non
      contrast) was 0.990+/-0.005%. The ratio of minimum dose Dmin(contrast)/Dmin(non
      contrast) and D95(contrast)/D95(non-contrast) were 0.970+/-0.030 and 0.984+/
      0.009, respectively. Contrast CT raised cord dose slightly. The ratio of cord
      Dmax was 1.005+/-0.026. However there were two cases the ratio of cord Dmax were
      1.035. CONCLUSIONS: The PTV D95 is usually normalized to prescription dose and
      the D95 differences between contrast and regular CT were within 2%. In most
      cases, the contrast CT could be used to treatment planning clinically. However
      more attention should be paid to maximum cord dose if it is already close to
      criteria limit.

PMID- 28518517
TI  - SU-E-T-556: Integration of Lung Blocks in the Inverse Planning Process of
      Modulated Arc Total Body Irradiation Using Cone Beam CT.
AB  - PURPOSE: The sizing and placement of lung blocks for total-body irradiation (TBI)
      is critical to prevent lung toxicities and maintain effective treatments. During
      modulated-arc TBI (MATBI) treatment, the patient is stationary near the floor
      while open-field beams with varying exposures are delivered. The inverse planning
      process currently aims for a uniform dose to the body, without accounting for the
      presence of lung blocks. This study investigates the possibility of including the
      effect of these blocks in the MATBI optimization process. METHODS: Dosimetric
      comparisons were performed using a water tank and a simple stack of solid water
      slabs. Lungs blocks made of cerrobend were fabricated and imaged using on-board
      megavoltage CBCT (MVCBCT). The reconstructed MVCBCT images were precisely
      registered with the reference CT for inverse planning. The cerrobend blocks were
      contoured in the planning system and the density was overridden to 9.3 g/cm3 .
      Simulated doses in Pinnacle were compared to ion chamber, diode array and gaf
      chromic film measurements obtained at 1.0, 5.0, 10.0 and 20.0 cm depths. Specific
      optimization objectives on the lungs were tested on 5 patients including a lung
      re-treatment. RESULTS: The maximum difference between ion chamber measurements
      and the treatment planning predictions was 2.4%. The measurements profiles with
      the diode array correlated reasonably well (<5%) with predictions. Gaf-chromic
      films demonstrated good accuracy at depth but large differences (>10%) on the
      surface. Lung blocks reconstructed with MVCBCT were structuraly accurate without
      significant metal artifacts. A comparison of MATBI plans on patients shows that
      inclusion of lung blocks during optimization can reduce hot and cold areas in the
      lungs and the sternum. CONCLUSION: Reasonable predictions of the lung block
      transmission can be obtained following the developed technique using megavoltage
      CBCT. Thus, lung blocks can be included in the MATBI inverse planning process,
      which can help prevent complications and local failure.

PMID- 28518516
TI  - SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA &
      CCC Algorithms for VMAT Technique.
AB  - PURPOSE: To dosimetrically validate AcurosXB algorithm for Volumetric Modulated
      Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic
      Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms.
      METHODS: AcurosXB dose calculation algorithm is available with Varian Eclipse
      treatment planning system (V10). It uses grid-based Boltzmann equation solver to
      predict dose precisely in lesser time. This study was made to realize algorithms
      ability to predict dose accurately as its delivery for which five clinical cases
      each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification
      plans were created on multicube phantom with iMatrixx-2D detector array and then
      dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and
      the same were delivered onto CLINAC-iX treatment machine. Delivered dose was
      captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference
      to quantify the agreement between AcurosXB calculation algorithm against
      previously validated AAA and CCC algorithm. Gamma evaluation was performed with
      clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro
      I'MRT software. Plans were evaluated in terms of correlation coefficient,
      quantitative area gamma and average gamma. RESULTS: Study shows good agreement
      between mean correlation 0.9979+/-0.0012, 0.9984+/-0.0009 & 0.9979+/-0.0011 for
      AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to
      be 98.80+/-1.04, 98.14+/-2.31, 98.08+/-2.01 and 2mm/2% was found to be 93.94+/
      3.83, 87.17+/-10.54 & 92.36+/-5.46 for AAA, CCC & Acuros respectively. Mean
      average gamma for 3mm/3% was 0.26+/-0.07, 0.42+/-0.08, 0.28+/-0.09 and 2mm/2% was
      found to be 0.39+/-0.10, 0.64+/-0.11, 0.42+/-0.13 for AAA, CCC & Acuros
      respectively. CONCLUSIONS: This study demonstrated that the AcurosXB algorithm
      had a good agreement with the AAA & CCC in terms of dose prediction. In
      conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative
      to AAA and CCC algorithms in a busy clinical environment.

PMID- 28518518
TI  - SU-E-T-527: Assessment of Field-Junction Dosimetry: Pinnacle V9.0 versus Film
      (EBT2).
AB  - PURPOSE: To investigate dose agreement of Pinnacle V9.0 with measurements across
      the junction between abutting photon and electron fields. METHODS: Photon-photon,
      photon-electron, and electron-electron field junctions of energies 6 MV and 9 MeV
      were evaluated with 0, 5, and 10 mm gaps between the field edges at depths of 2,
      15, and 30 mm with Gafchromic film (EBT2). Photon and electron fields (10*10 cm)
      were setup to deliver 300 cGy in their field centers to 30 mm depth. Film optical
      density was measured every millimeter across the field-junction with a
      densitometer (light beam 2 mm). Optical Density to dose conversion was
      accomplished using a calibration curve specific to the batch of this film. For
      comparison, all field combinations were generated in Pinnacle, and doses were
      calculated with collapsed-cone convolution algorithm employing calculation-grid
      sizes 2, 3, and 4 mm. RESULTS: Measured doses at junction are as much as 20%
      different than Pinnacle calculation. 3 profiles with zero gap, 1 profile with 0.5
      cm gap, and 0 profiles with 1.0 cm gap showed a disagreement greater than 12%.
      Measurement showed a bias towards higher dose in the junction when compared to
      Pinnacle calculation. With dose-calculation grid reduced below 4 mm, Pinnacle
      calculations showed improved agreements, but only a few percent at most. Pinnacle
      versus measured dose disagreements do not show clear trends with field separation
      or depth. CONCLUSIONS: Doses calculated by Pinnacle V9.0 in the field-junction
      region may not be accurate for abutting photon and electron fields, particularly
      when a coarse dose-calculation grid is utilized. Lack of clear trends in dose
      agreement with field separation and depth suggests that uncertainties in other
      factors such as jaw positions and phantom set-ups may be additional contributors.
      Significant inaccuracies in doses reported by the treatment-planning system in
      field-junction region should be considered while making clinical decisions.

PMID- 28518519
TI  - SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA
      Algorithms.
AB  - PURPOSE: To evaluate the accuracy of dose calculation for intensity modulated
      radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic
      Algorithm (AAA) computation algorithms. METHODS: IMRT plans of twelve patients
      with different treatment sites, including head/neck, lung and pelvis, were
      investigated. For each patient, dose calculation with PB and AAA algorithms using
      dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite
      beam ion chamber and film measurements in patient specific QA. Discrepancies
      between the calculation and the measurement were evaluated by percentage error
      for ion chamber dose and gamma>l failure rate in gamma analysis (3%/3mm) for film
      dosimetry. RESULTS: For 9 patients, ion chamber dose calculated with AAA
      algorithms is closer to ion chamber measurement than that calculated with PB
      algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are
      within 3% of the measurements. For head/neck patients and other patients with
      large treatment volumes, gamma>l failure rate is significantly reduced (within
      5%) with AAA-based treatment planning compared to generally more than 10% with PB
      based treatment planning (grid size=2.5 mm). For lung and brain cancer patients
      with medium and small treatment volumes, gamma>l failure rates are typically
      within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For
      both PB and AAA-based treatment planning, improvements of dose calculation
      accuracy with finer dose grids were observed in film dosimetry of 11 patients and
      in ion chamber measurements for 3 patients. CONCLUSION: AAA-based treatment
      planning provides more accurate dose calculation for head/neck patients and other
      patients with large treatment volumes. Compared with film dosimetry, a gamma>l
      failure rate within 5% can be achieved for AAA-based treatment planning.

PMID- 28518520
TI  - SU-E-T-504: Incident Fluence Reconstruction Based on Monte Carlo Finite-Size
      Pencil Beam Model for Dose Guided Radiation Therapy.
AB  - PURPOSE: In dose guided radiation therapy, incident fluence is one of the
      important parameters for both influence verification and dose reconstruction. The
      objective of this investigation was to develop a method to obtain the incident
      fluence for dose reconstruction in dose guided radiation therapy (DGRT). METHODS:
      An incident fluence reconstruction model based on Monte Carlo Finite-size pencil
      beam (MCFSPB) model and "Matthew Effect" Conjugate-gradient (CG) algorithm was
      developed, where the MCFSPB model was developed by FDS Team (www.fds.org.cn) and
      the "Matthew Effect" was proposed to advance the accuracy of CG lgorithm. Then,
      by measuring dose with amorphous silicon flat panel (a-Si flat panel), the
      incident fluence was unfolded. An artifical head phantom was used to test sample.
      By using the incident fluence to dose calculation with MCFSPB, the 2D and 3D dose
      was also reconstructed and compared with the measurement dose and the planing
      dose respectively. The Passing Rate of Dose Difference (PRDD) in 3% was used to
      learn the accuracy. RESULTS: Two representative cases (6MV and 10MV) with both
      five beams were used for beam-by-beam verification, and the corresponding
      incident fluence was obtained. By comparing the measurement dose with the
      calculation dose on measurement plane, the results showed that the PRDD (3%) in
      field was 100%. And by comparing 3D plannning dose with 3D reconstructed dose,
      the results indicated that the PRDD (3%) in field was 95%~98%. CONCLUSIONS: The
      incident fluence reconstruction model based on MCFSPB model and "Matthew Effect"
      Conjugate-gradient algorithm was developed. The tested results indicated its
      accuracy. This study is expected to be applied to 3D dose reconstruction and 3D
      dosimetric verification in DGRT. Supported by the National Natural Science
      Foundation under grant No.30900386 and the National Science Foundation of Anhui
      Province (Nos.090413095 and 111040606Q55).

PMID- 28518521
TI  - SU-E-T-549: On Importance of Accurate Treatment Couch Modeling in SmartArc VMAT
      Plans.
AB  - PURPOSE: We investigate the impact of a treatment couch and its modeling in a
      treatment planning system on accurate dose delivery in Volumetric Modulated Arc
      Therapy (VMAT). METHODS: A cone-beam CT of a Varian couch on a Varian Clinac 21EX
      unit, consisting of a carbon-fiber imaging couch top and supporting rails, was
      acquired, and a couch model was created in Philips Pinnacle 9.0 TPS based on the
      geometry of the couch top and the rails. The densities of the modeled couch top
      and the rails were based on the Hounsfield Unit and CT number-to-density
      information obtained from the CBCT scan. The densities were then adjusted based
      on the ion chamber measurements of a beam transmitting through the couch
      posteriorly at different gantry angles varying 1-5 degrees. SmartArc VMAT plans
      for patient treatment with and without the modeled couch were then generated and
      dose distributions were verified using the IBA MatriXX 2D ion chamber array.
      RESULTS: We found that depending on the gantry angle the beam can be attenuated
      by up to 17% when going through the supporting rails, and up to 5% when passing
      through the couch top. Because of this, dose distributions of SmartArc plans were
      not accurate and did not pass the dose verification criteria without accurate
      modeling of the treatment couch. Adding the couch model remedies this problem and
      avoids underdosing the target. CONCLUSIONS: We showed that the impact of a
      treatment couch in radiation therapy can be significant, and it is essential to
      include an accurate model of the couch in the treatment planning system,
      particularly for SmartArc VMAT plans in Philips Pinnacle TPS.

PMID- 28518522
TI  - SU-E-T-520: Quantitative Evaluation of Metal Artifacts in CT and Cone-Beam CT
      Images on the Accuracy of Dose Calculation.
AB  - PURPOSE: To investigate effects of metal artifacts on the dose calculation
      accuracy of three dose calculation algorithms on CT and cone-beam CT images.
      METHODS: A phantom with and without metal objects was scanned using CT simulator
      and on-board kV CBCT. Conformal 5-field treatment plans with identical physical
      and dosimetric parameters were created in the EclipseTM treatment planning system
      for CT and CBCT images. The beams were designed to avoid entering through
      metallic object. Three dose calculation algorithms were used in the plans: (a)
      pencil beam convolution with modified Batheo (PBC-MB), (b) equivalent TAR (PBC
      ET), and (c) analytical anisotropic algorithm (AAA). The dose calculation on the
      phantom CT images without metal was used as reference to compare with doses
      calculated using scans with metal objects. The gamma analysis and percentage dose
      differences were used to quantify the dosimetric effects of image artifacts from
      metal on CT and CBCT numbers. RESULTS: The dose difference analysis shows that
      mean percentage dose differences (MPDD) for CBCT with metal artifacts ranged from
      -0.12% to -0.26% with an average of -0.20% for PBC-MB, -0.25% to -0.39%, with
      average -0.31% for PBC-ET, and -0.25 to -0.84%, with average -0.62% for AAA for
      all planes. The PBC-MB showed the least difference in dose and highest gamma
      passing rates with the AAA consistently having the highest differences and lowest
      gamma passing rates. This might result from accurate consideration of scattered
      dose in heterogeneities by AAA. All MPDD for doses calculated on CT and CBCT
      using different dose calculation algorithms were not significant (within 1%).
      CONCLUSION: The image artifacts due to streaking from metal objects were
      generally small (within 1%) for the dose calculated using the different treatment
      planning algorithms on CT and CBCT images. Furthermore, the dose difference from
      CT-number variation between CBCT and CT were negligible.

PMID- 28518523
TI  - SU-E-T-508: A Novel Method of Heterogeneity Compensation for the Convolution /
      Superposition Algorithm.
AB  - PURPOSE: We developed a better method of accounting for the effects of
      heterogeneity in convolution algorithms. We integrated this method into our GPU
      accelerated, multi-energetic convolution/superposition (C/S) implementation. In
      doing so, we have created a new dose algorithm: heterogeneity compensated
      superposition (HCS). METHODS: Convolution in the spherical density-scaled
      distance space, a.k.a. C/S, has proven to be a good estimator of the dose
      deposited in a homogeneous volume. However, near heterogeneities electron
      disequilibrium occurs, leading to faster fall-off and re-buildup than predicted
      by C/S. We propose to filter the actual patient density in a position and
      direction sensitive manner, allowing the dose deposited near interfaces to be
      increased or decreased relative to traditional C/S. We implemented the effective
      density function as a multivariate first-order recursive filter. We compared HCS
      against traditional C/S using the ICCR 2000 Monte-Carlo accuracy benchmark, 23
      similar accuracy benchmarks and 5 patient cases. For the patient cases, we
      created custom routines capable of using the discrete material mappings used by
      Monte-Carlo. C/S normally considers each voxel to be a mixture of materials based
      on a piecewise-linear density look-up table. RESULTS: Multi-energetic HCS
      increased the dosimetric accuracy for the vast majority of voxels; in many cases
      near Monte-Carlo results were achieved. HCS improved the mean Van Dyk error by
      0.79 (% of Dmax or mm) on average for the patient volumes; reducing the mean
      error from 1.93%|mm to 1.14%|mm. We found a mean error difference of up to 0.30
      %|mm between linear and discrete material mappings. Very low densities (i.e. <0.1
      g / cm3 ) remained problematic, but may be solvable with a better filter
      function. CONCLUSIONS: We have developed a novel dose calculation algorithm based
      on the principals of C/S that better accounts for the electron disequilibrium
      caused by patient heterogeneity. This work was funded in part by the National
      Science Foundation under Grant No. EEC9731748, in part by Johns Hopkins
      University internal funds and in part by Elekta.

PMID- 28518524
TI  - SU-E-T-511: Dose Variations Related to Tumor Size and Location for Pencil Beam
      and Anisotropic Analytical Algorithms.
AB  - PURPOSE: To investigate the tumor geometric relationship to the dose variations
      of Anisotropic Analytical Algorithm (AAA), pencil beam convolution algorithm
      with/without modified Bath Power Law(PBMPL)/PB in stereotactic body radiation
      therapy(SBRT) treatment plans of patients presenting with a solitary primary lung
      cancer. MATERIALS/METHODS: Treatment plans of 14 patients (7 upper lobe, 7 lower
      lobe) were used for this study. The planning target volume (PTV) size ranges from
      3.9c.c. to 156.7c.c. The SBRT treatment plans were composed of 10-12 non-
      coplanar photon beams as per RTOG guidelines. The prescription dose for this
      study were (i) 4*12Gy, (ii) 5*10Gy, and (iii) 5*11Gy. The Varian Eclipse
      treatment planning system Eclipse v. 8.9 (Palo Alto, CA) was used for this study.
      Four-dimensional CT (4D CT) data were used to define the integral target volume
      (ITV) on maximum intensity projection. An 5mm circumferential margin was used to
      create PTV from ITV. Plans were generated with three algorithms. RESULTS: a). For
      small lesions (PTV occupy less than 1% of the ipsilateral lung volume), the PBMPL
      plans had overestimated the dose by average 10% compared to AAA. But the PB
      without any heterogeneity correction agrees well with AAA. b). For big lesions
      (PTV occupy more than 1% of the ipsilateral lung volume), the PBMPL plans had
      agreed well with AAA. But the PB without any heterogeneity correction
      underestimate the dose by average 15% compared to AAA. c). The tumor location
      (Group1: within 1cm from the lung wall;Group2: 2cm away from the lung wall
      Group3: in between zone of 1 and 2cm from the lung wall; Group 4:Spread from the
      lung wall to the 2cm away zone) seems to relate with dose calculation variations
      among different algorithms. CONCLUSIONS: Prescription adjustment is not necessary
      for PTV less than 1% of ipsilateral lung volume as the recent suggestion by the
      quality assurance working group of phase III Rosel study of prescription dose
      reduction of 10% from 60Gy to 54Gy when utilizing AAA instead of PBC.

PMID- 28518525
TI  - SU-E-T-551: A Customized Plan Evaluation System for On-Line Adaptive
      Radiotherapy.
AB  - PURPOSE: Treatment plan evaluation based on daily images, to determine whether it
      is necessary to re-plan the treatment, is an essential element of adaptive
      radiotherapy. A fully automatic system, incorporating physician preferences and
      requirements of specific protocols quantified by a series of objective functions,
      was developed to evaluate treatment plans. METHODS: The evaluation system was
      developed using IDL 6.1 (ITT Visual Information Solutions, Boulder, CO). Based on
      customized evaluation guidelines, dosimetric parameters, including maximum dose,
      minimum dose, uniformity dose, dose coverage, conformity index, heterogeneity
      index, gEUD, and DVH for the targets and OARs are evaluated as series of cost
      functions which incorporate specific protocol constraints and physician
      requirements. The evaluation system was applied to IMRT plans of head/neck cancer
      patients. The Pinnacle Treatment Planning System (research version 9.0) was used
      to generate verification treatment plan trials, with image datasets, ROI
      structures, and dose distributions exported to evaluation system. RESULTS:
      Results show that the evaluation system can complete evaluation of a dose plan
      within 2~8 seconds. The system is capable of displaying and comparing dose
      distributions among different plans. It also demonstrates great flexibility in
      customizing cost functions based on physician preferences. This system is
      supported with various user-friendly options, graphical displays, and feasibly
      structure in adding new modules. CONCLUSIONS: This evaluation system is capable
      of quantifying specific protocols and preferences of physicians and completing
      automatic evaluation almost in real-time. It is an essential a platform for
      adaptive radiation therapy and also valuable for initial treatment planning. This
      research is supported by CPRIT Individual Investigator Award RP110329.

PMID- 28518526
TI  - SU-E-T-522: Analysis of SCERMA-to-KERMA Ratio for Megavoltage Photons.
AB  - PURPOSE: To examine the relationship between the primary SCERMA, Sp, and the
      primary collision KERMA, Kcp, as a function of depth for clinically relevant
      energy spectra, and to accurately model the SCERMA to KERMA ratio (SKR) for
      clinical photon beams. METHOD AND MATERIALS: Sp, Kcp, Sp / Kcp (=SKR) for the
      energy spectra of Cobalt-60 (Co-60), and Mohan 4 MV, 6 MV, 10 MV, 15 MV, and 24
      MV photons are analytically calculated over depths from 0 to 40 centimeters in
      water. The Sp and Kcp are fitted to exponential functions, Sp0exp(-MU'd(l-eta'd))
      and Kp0exp(-MUd(l-etad)), respectively, with depth d, linear attenuation
      coefficient MU and beam hardening coefficient eta; MU' and eta' are the
      corresponding quantities for Sp. The relationships between MU', eta', and SKR vs.
      MU are examined. Trends between the fitting parameters and MU were also
      determined, and the results applied to model the SKR of 6* and 15* clinical beams
      as functions of only MU, eta, and depth. RESULTS: SKR decreases with depth for
      all spectra. We found MU' = (0.80496 + 4.8748MU)MU + 0.005736 and eta' = (
      0.13076 + 2.6571MU)MU + 0.0036151 for 0.0273/cm<=MU<0.0392/cm, and MU' =
      0.87718MU + 0.010864 and eta' =(-0.009 - 0.50122MU)MU + 0.0037 for 0.0392/cm <=
      MU <= 0.0667/cm. This model predicts the normalized SKR/(SKR(d=0)) with a
      relative deviation of 0.1% and max deviation of 1%. SKR/(SKR(d=0)) from clinical
      beams 6* and 15* is examined to be in agreement with analytic computation from
      spectral data with 1% and 0.5% maximum error, respectively. CONCLUSION: Knowledge
      of normalized SKR is a necessary to calculate scatter dose accurately. We have
      developed an empirical model to calculate the normalized SKR to be used for
      clinical (scatter) dose calculation and consequently improve dose calculation
      accuracy.

PMID- 28518527
TI  - SU-E-T-533: Evaluating Effective Source Position Corrections during Modeling with
      Pinnacle Version 9.2 Software for Flattening Free (FFF) Small Field Treatments.
AB  - PURPOSE: Advanced treatment delivery techniques require more robust treatment
      planning system (TPS) models for accurate dose planning and computation. As
      stereotactic body radiation therapy (SBRT) and volumetric-modulated arc therapy
      (VMAT) treatments become more prevalent, the ability of the TPS to accurately
      calculate dose delivered from small fields becomes of greater importance. An
      additional level of complexity in photon beam modeling is added with the
      inclusion of flattening filter free (FFF) treatment beams, due to steep in field
      dose gradients and non uniform penumbra regions. The purpose of this work is to
      examine the ability of ADAC/Pinnacle TPS to accurately model and calculate dose
      from small field FFF treatment beams. METHODS: Photon beam data was first modeled
      using Pinnacle v9.0. Flattened and FFF beam models were generated for 6MV and
      10MV energies. Models were fine-tuned using a 5*5 cm2 field as the standard field
      in order to place more emphasis on the accuracy of the model for the small
      fields. An upgrade to Pinnacle v9.2 allowed for comparison between version 9.0
      and version 9.2. RESULTS: Accurately modeling small fields using Pinnacle v9.0
      proved difficult, particularly in the lower penumbra region. An asymmetry
      appeared in the small field models for both the flattened and FFF models. The
      Pinnacle v9.2 upgrade eliminated the small field asymmetries, and allowed for
      more accurate penumbra region calculations. Preliminary results have shown that
      Pinnacle v9.2 is capable of developing accurate beam models when an emphasis is
      placed on the small fields. In addition, patient specific dosimetric information
      for version 9.0 and version 9.2 was also calculated and examined for prostate,
      head & neck, and lung treatments. CONCLUSIONS: Pinnacle v9.2 showed improved
      accuracy in small field FFF dose modeling over version 9.0. Comparison of patient
      dosimetric information reflected the improvement in the small field modeling.

PMID- 28518528
TI  - SU-E-T-544: Commissioning and Clinical Evaluation of a Secondary Check Software
      for 3D Conformal and IMRT Treatment Plans.
AB  - PURPOSE: The increasing complexities of the geometry of 3D radiation treatment
      plans possess challengesto the monitor unit (MU) and dose verification in
      clinical routine. In this work, the commissioningof the DIAMOND software (PTW
      Freiburg Germany) for two Siemens linear accelerators(Primus & Artiste) along
      with the evaluation of its performance is described. METHODS: DIAMOND employs the
      modified Clarkson integration method for dose computation and a pointeye-view
      (PEV) method for scatter calculation on collimators by a geometrical back
      projectinginto the collimation system from the view of the source. During the
      commissioning process, themachine data (geometrical set up) and dosimetry base
      data such as the percentage depth dose(PDD), head scatter factor Sc as well as
      total scatter factor Sc,p, off-axis profiles are entered into the software. A
      comprehensive validation process is performed following the provided protocol.For
      evaluation purposes, twelve 3D conformal treatment plans and two prostate IMRT
      plans arecalculated with DIAMOND and the results are compared to the values from
      the treatmentplanning system (TPS). RESULTS: The deviations of the MU for 3D
      conformal treatment plans computed with the DIAMONDsoftware are within +/-3%. For
      IMRT plan verification, the dose at a point in the target volume iscomputed for
      every treatment beam, with deviations within 0.40% to 3.28%. The typical time
      forsingle dose point verification is less than a minute, thus minimizing the
      clinical workload of theverification process. For dose matrices calculation at
      certain plane, a relative longercomputation time is needed depending on a field
      dimension. CONCLUSIONS: In this work, we have demonstrated the ability of the
      DIAMOND software to compute MU anddose at a point for 3D conformal and IMRT
      plans. Its speed and accuracy implies that DIAMOND can be implemented as
      independent secondary check software in the clinical routine.

PMID- 28518529
TI  - SU-E-T-515: Comparison of Two Dose-Specification Methods for the Treatment of
      Uterine Cervix Cancer with HDR Brachytherapy Using a Tandem and Ring Applicator.
AB  - PURPOSE: To compare the dose to the high-risk clinical target volume (HRCTV)-D90
      and dose-limiting structures with the dose prescription to point A (Manchester
      system) using conventional methods to image-guided treatment planning with dose
      optimization and a dose prescription to D90 of the HRCTV. METHODS: CT-MR-fused
      image sets for 16 patients (stage IA2-IIIB) with uterine cervix cancer were
      obtained for each of 5 fractions of HDR brachytherapy using tandem and ring
      applicators to generate 2 sets of plans. In the first set, the dose was
      prescribed to point A with a standard dwell weight pattern reflecting the
      Manchester system loading pattern. In the second set, the dose was prescribed to
      D90 of the HRCTV with graphical plan optimization. Parameters of clinical
      significance (HRCTV-D90 and dose received by 1.0, 2.0, and 5.0cc of the bladder,
      rectum, and sigmoid) were compared, as recommended by GEC-ESTRO. RESULTS: HRCTV-V
      for 6 patients was =30cc (largest radius, <2.0cm) and >30cc (largest radius,
      =2cm) for the others. For the first set of plans, when HRCTV-V was <30cc, the
      ratio of doses HRCTV-D90/dose to point A varied from 1.10 to 1.40. When HRCTV-V
      was >30cc, it varied from 0.75 to 0.95. In the second set of plans, HRCTV-D90
      always received the prescription dose. Doses to 2cc of one or more organs at risk
      exceeded >10% of the limiting doses for 9 patients in the first set of plans but
      remained <10% in all patients in the second set of plans. A 10-25% dose reduction
      to 2cc of the bladder and 15-35% to 2cc of the rectum and sigmoid occurred in the
      second set of plans. CONCLUSIONS: Image-guided brachytherapy with dose
      optimization yields a prescribed dose to the HRCTV-D90 while maintaining doses to
      organs at risk close to their limiting value, offering a dosimetric benefit over
      the traditional method.

PMID- 28518530
TI  - SU-E-T-555: Weighted Four-Dimensional IMRT Planning for Dynamic MLC Tracking
      Using a Practical and Simple Framework.
AB  - PURPOSE: We present a simple, practical framework for truly 4D lung IMRT planning
      based on a weighted individual-phase optimization paradigm. This strategy is
      specifically developed for use in real-time tumor tracking delivery systems so as
      to utilize respiratory motion as an additional degree of freedom rather than a
      constraint. METHODS: A 4D-CT scan from a lung SBRT patient was loaded into the
      Eclipse treatment planning system. The target and normal structures were manually
      contoured on each of the ten phases. For each phase, the total dose prescription
      was scaled by the number of phases and a seven-field plan was developed. An open
      source deformable image and dose registration engine (DIRART) was used to deform
      the dose map at each phase to a reference phase. DVH data from the individually
      optimized phase plans were input into an in-house linear programming-based
      optimizer implemented in MATLAB, in order to determine dose-weighting factors for
      each phase. The objective function aimed to maintain PTV coverage while keeping
      normal structure dose as low as possible. This weighted-4D plan (W-4D) was
      compared to an ITV-based plan and a 4D plan with equal dose-weights to individual
      phases (E-4D). RESULTS: The W-4D dose fractions were determined to be 0.33, 0.01,
      0.65 and 0.02 at phase 0%, 30%, 40%, and 90%, respectively (and zero elsewhere).
      PTV coverage (V95) was close to identical for all three strategies. The W-4D plan
      exhibited mean lung dose 18.8% and 8.5% lower and mean liver dose 23.3% and 5.7%
      lower than corresponding values from ITV-based and E-4D plans, respectively.
      CONCLUSIONS: By significantly improving normal structure sparing while
      maintaining PTV coverage, weighted 4D planning represents a more attractive
      solution than ITV-based planning for (currently investigational) real-time tumor
      tracking-based delivery systems.

PMID- 28518531
TI  - SU-E-T-526: Evaluation of Dose Mapping Errors via Use of a Volume-Based Dose
      Mapping Method.
AB  - PURPOSE: To quantify dose mapping errors (DMEs) of a point-based dose mapping
      method for 4D lung treatment plans. METHODS: Point-based dose mapping methods
      utilize deformation vector fields (DVFS) to interpolate dose from a deformed
      image. Volume-based dose mapping methods consider the volume overlap between
      deformed and reference voxels; defining dose as the integral energy divided by
      the integral mass of the voxel, and conserving integral dose . DME is defined as
      the dose differences between volume-based and point-based mapped dose
      (DME=(DpointBased-DvolumeBased)/DRx). The DME for a 4D lung case is compared with
      a bitmap DME method, both using a Pinnacle research version 8.1y DVF. DME is
      computed for ten 4D lung cases (five 10 phases, five 3 phase) with Pinnacle
      research version 9.100 DVFs. Multi-phase accumulated 4D DMEs are also evaluated.
      RESULTS: For all cases, the largest DMEs are located in the dose/density gradient
      regions. With Pinnacle 8.1y DVF, mapping dose from phase 9 to phase 0, results in
      a DME=-0.2%+/-6.1% (range of -76%~112%). The same case with Pinnacle 9.100 DVFs,
      DME=0.3%+/-4.8%(-41%~32%). Locations of large DME are consistent with those from
      the bitmap method. For the ten 4D lung cases, accumulated mean DME are within +/
      0.07% (std. deviations: 1~5%, range -102%~64%). Maximum tumor DMEs are less than
      30cGy (DRx=7200cGy) for all patients. CONCLUSIONS: Due to its inherent integral
      dose conservation, volume-based dose mapping methods can quantify errors in point
      based dose mapping methods. While mean DME values are small for the cases tested,
      standard deviations near 5% indicate that a substantial number of voxels have ~5%
      dose mapping errors, however these dose errors do not occur in the target
      structures. Work supported by NIH P01CA116602.

PMID- 28518532
TI  - SU-E-T-537: Photon Beam Modeling and Verification of Collapsed Cone Convolution
      Algorithm for Dose Calculation in a Radiation Treatment Planning System.
AB  - PURPOSE: The aim of this study is to evaluate the accuracy the collapsed cone
      convolution (CCC) algorithm for dose calculation in a radiation treatment
      planning system (TPS). METHODS: We modeled various photon beams for various setup
      conditions in a radiation treatment planning system (CorePLANTM, Seoul C&J,
      Korea). The beam models were generated at various set-up conditions such as open
      beam or wedged beam, 6 MV or 15 MV beam and field sizes from 4*4 cm2 to 40 * 40
      cm2 . Each beam model was optimized by spectrum modeling from measured percent
      depth dose (PDD) data, dose profile modeling from a measured profile at a
      specific depth (10 cm) data. Dose calculation was performed using conventional
      CCC algorithm. All measured data were acquired from a Clinac 21EX (Varian Medical
      System, Palo Alto, CA, USA) linear accelerator with the setting of SSD = 100 cm.
      All calculated PDD and dose profiles at various depths from generated beam models
      were compared to the measured data. RESULTS: Calculated dose data from each beam
      model showed good agreements within 2% of difference to the measured PDD and
      within 3% dose profiles at various depths. Some regions such as penumbra region
      at 20 * 20 cm2 field size and horn region at wedge field showed dose
      discrepancies over 3%. The results of PDD at all situations showed well agreement
      with measured data under the 10*10 cm2 field size. For wedged cases, however,
      under the 5 cm depths, some inconsistency at penumbra region were appeared.
      CONCLUSIONS: In this study, we verified the accuracy of CCC algorithm in the TPS.
      Calculated results by our implemented algorithm was well satisfied with measured
      dose at small field size (<20 7 times; 20 cm2 ). Our next study will perform to
      compensate theses inconsistencies.

PMID- 28518533
TI  - SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of
      Statistical Uncertainty.
AB  - PURPOSE: With the development of ultra-fast GPU-based Monte Carlo (MC) dose
      engine, it becomes clinically realistic to compute the dose-deposition
      coefficients (DDC) for IMRT optimization using MC simulation. However, it is
      still time-consuming if we want to compute DDC with small statistical
      uncertainty. This work studies the effects of the statistical error in DDC matrix
      on IMRT optimization. METHODS: The MC-computed DDC matrices are simulated here by
      adding statistical uncertainties at a desired level to the ones generated with a
      finite-size pencil beam algorithm. A statistical uncertainty model for MC dose
      calculation is employed. We adopt a penalty-based quadratic optimization model
      and gradient descent method to optimize fluence map and then recalculate the
      corresponding actual dose distribution using the noise-free DDC matrix. The
      impacts of DDC noise are assessed in terms of the deviation of the resulted dose
      distributions. We have also used a stochastic perturbation theory to
      theoretically estimate the statistical errors of dose distributions on a
      simplified optimization model. RESULTS: A head-and-neck case is used to
      investigate the perturbation to IMRT plan due to MC's statistical uncertainty.
      The relative errors of the final dose distributions of the optimized IMRT are
      found to be much smaller than those in the DDC matrix, which is consistent with
      our theoretical estimation. When history number is decreased from 108 to 106, the
      dose-volume-histograms are still very similar to the error-free DVHs while the
      error in DDC is about 3.8%. CONCLUSIONS: The results illustrate that the
      statistical errors in the DDC matrix have a relatively small effect on IMRT
      optimization in dose domain. This indicates we can use relatively small number of
      histories to obtain the DDC matrix with MC simulation within a reasonable amount
      of time, without considerably compromising the accuracy of the optimized
      treatment plan. This work is supported by Varian Medical Systems through a Master
      Research Agreement.

PMID- 28518534
TI  - SU-E-T-548: Case Study of HDR Vs IMRT in Pediatric Sarcomas.
AB  - PURPOSE: To compare the dose to critical structures using HDR brachytherapy
      versus IMRT in pediatric tumors. METHOD: Two sarcoma cases, for which both HDR
      and IMRT could be options, were selected for this case study. Case 1 targeted a
      volume on the posterior neck/upper back with an HDR prescription of 600cGy * 5
      fractions, 3000cGy total. The IMRT prescription used was 180cGy * 25 fractions,
      4500cGy total with a boost of 180cGy * 6 fractions, 1080cGy. The IMRT PTV used
      was a 0.5cmexpansion of the HDR PTV; the boost PTV was identical to the HDR
      treatment plan. Case 2 targeted a volume on the palette of the mouth with an HDR
      prescription of 300cGy * 12 fractions, 3600cGy total. The IMRT prescription used
      was 180cGy * 28 fractions, 5040cGy total. A 0.5cm expansion of the HDR PTV was
      used for the IMRT PTV. In both cases, for both HDR and IMRT, at least 95% of the
      PTV received 100% prescription dose, following Children's Oncology Group
      protocols. RESULTS: Case 1 : the mean doses to the body, brachial plexus,
      esophagus, spinal cord and thyroid were higher using IMRT than HDR. Integral dose
      was 6.6 times higher using IMRT than HDR. Case 2: the mean doses to the body,
      mandible, and parotids were higher using IMRT than HDR. Integral dose was 2.9
      times higher using IMRT than HDR. CONCLUSION: This study shows the potential
      benefit of treating with HDR compared to IMRT in select pediatric cases. These
      results suggest that HDR can be superior to IMRT in the sparing of critical
      structures and in delivering less integral dose to the patient while still
      achieving adequate target coverage. However, lower mean doses to critical
      structures must also be weighed against the possibility of complications from
      HDR's very high hotspots.

PMID- 28518535
TI  - SU-E-T-519: Experimental Evaluation of Deterministic Acuros XB Radiation
      Transport Algorithm for Heterogeneity Dose Calculation Using the Radiological
      Physics Center's Lung Phantom.
AB  - PURPOSE: To evaluate the heterogeneity corrected dose calculations from the
      Acuros XB (AXB), a novel deterministic dose calculation algorithm based on grid
      based Boltzmann transport equation solver (GBBS), for IMRT and VMAT plans.
      METHODS: The Radiological Physics Center's lung phantom was used to create
      clinically equivalent IMRT and VMAT plans (RapidArc) with the Eclipse planning
      system 10.0 that were delivered using a Varian 23 iX. Absolute doses and relative
      dose distributions were measured with thermoluminescent dosimeters (TLDs) and
      radiochromic film. The measured dose distributions were compared with calculated
      doses from both AXB (11.0.3) and AAA (10.0.24) dose calculation algorithms. The
      AXB calculated dose-to-water and dose-to-medium were both compared to
      measurements. Gamma analysis (+/-7%/4mm, +/-5%/3mm, and +/-3%/3mm) was used to
      quantify correspondence between AXB dose distributions and the film measurements.
      The computation time between AAA and AXB were also evaluated. RESULTS: For TLD
      point doses, both AAA and AXB heterogeneity corrected dose calculations are
      within 5% inside the PTV for both IMRT and VMAT plans. The agreements observed
      between the measured and calculated doses for both AXB dose reporting methods are
      better than those observed with the AAA algorithm. The gamma analysis showed that
      the differences between AAA, AXB and film measurement met the RPC +/-7%/4 mm
      criteria. The percent of pixels passing rate for both the AXB dose to medium and
      AXB dose to water are higher than AAA. The computation time between AAA and AXB
      are comparable for IMRT plans but AXB is significantly faster (4 times) than AAA
      for VMAT plans. CONCLUSIONS: The AXB implemented in the Eclipse planning system
      calculates a more accurate heterogeneity corrected dose than the AAA algorithm as
      compared to measurement in lung and improve the calculation speed for VMAT
      radiotherapy. Work supported by grants CA10953, CA81647, 2R44CA105806-02,
      CA016672 (NCI, DHHS).

PMID- 28518536
TI  - SU-E-T-530: Relative Electron Density Phantom Comparison.
AB  - PURPOSE: Modern treatment planning systems require lookup tables to convert
      Hounsfield Units (HU) to relative electron density (RED) for use in heterogeneity
      corrections during dose calculations. The purpose of this work is to illustrate
      the impact of using different model CT phantoms to determine HU to RED curves for
      treatment planning. METHODS: A GAMMEX model 467 tissue characterization phantom
      and a CATPHAN model 500 multipurpose CT phantom were imaged using CT scanners in
      four different cancer centers and the HU to RED curves derived from each phantom
      were imported into an Eclipse 8.10 treatment planning system. Dose calculation
      were performed on a heterogeneity phantom and then compared to measurements. A
      comparison of isodose and DVH were performed by calculating 3D and IMRT plans
      onto identical CT datasets with different HU to RED curves to determine the
      clinical significance. Analysis based on effective atomic number of the phantom
      inserts was also performed. RESULTS: The HU to RED curves from the GAMMEX and
      CATPHAN phantoms were found to be reasonably self-consistent across the different
      CT scanners. However, observable differences for higher density materials were
      observed between the two phantom models. The differences for the larger HU values
      can be attributed to the effective atomic number of the materials. In kV range of
      a CT scanner x-ray spectrum, photon interactions are partially due to the
      photoelectric effect which has a larger dependence on atomic number than Compton
      scatter which depends most directly on electron density. CONCLUSION: The HU to
      RED curve is more dependent on the phantom model than CT scanner. The HU to RED
      curve from the GAMMEX phantom produced better agreement between Eclipse AAA
      calculations and measured dose distributions on a heterogeneity phantom than that
      from the CATPHAN. However, DVH and isodose data on patient plans show small
      differences for common treatment sites.

PMID- 28518537
TI  - SU-E-T-507: Dose Calculation Quality of AcurosXB Involving a HD120 MLC Compared
      with Monte Carlo Methods.
AB  - PURPOSE: Advanced radiation therapy requires highly sophisticated dose
      calculation algorithms such as finite element based Boltzmann solvers or Monte
      Carlo (MC) methods. MC is commonly accepted as the golden standard method for
      dose calculation in high energy treatments and thus it is used for benchmarking
      other algorithms. In this work the quality of dose distribution calculated using
      the Boltzmann solver based AcurosXB algorithm within Eclipse (Varian Medical
      Systems) is investigated for volumetric modulated arc treatment (VMAT) plans
      involving the high definition MLC (HD120 MLC) by comparing doses with the
      validated Swiss Monte Carlo Plan (SMCP). MATERIALS & METHODS: Within SMCP and
      Eclipse using AcurosXB, 10 VMAT H&N patient plans and corresponding verification
      plans were recalculated using fixed MUs. In SMCP, radiation transport and dose
      calculation were performed using VMC++ with a statistical uncertainty of 1%. The
      voxel size was 2.5 mm for SMCP and AcurosXB and the same material composition
      data was used for CT conversion. Dose volume histograms (DVH) were used in order
      to quantify the difference between the dose distributions of the patient plans.
      In addition, calculated verification plans were compared with measurements
      carried out with the Delta4 system (Scandidos) by using the gamma evaluation with
      3%/3 mm criteria of points having a dose larger than 20% of isocenter dose.
      RESULTS: DVHs for the patient plans showed good agreement between SMCP and
      AcurosXB calculations. Overall AcurosXB lead to an underestimation of the median
      dose values by about 1%. For measured total dose distributions of the
      verification plans on average 98.6% and 99.0% of the points fullfil the gamma
      criteria for the dose calculated using AcurosXB and SMCP, respectively.
      CONCLUSIONS: Resulting AcurosXB dose distributions for VMAT H&N plans involving a
      HD120 MLC are in good agreement with calculated SMCP dose distributions. CONFLICT
      OF INTEREST: This work was supported by Varian Medical Systems.

PMID- 28518657
TI  - TU-E-BRB-11: End-To-End Positioning Quality Assurance for Image-Guided
      Radiosurgery of Multiple Targets Using a Single-Isocenter.
AB  - PURPOSE: Using a single isocenter significantly reduces delivery times in
      radiosurgery involving multiple targets. However, because not every target can be
      placed at isocenter with this type of treatment, a conventional Winston-Lutz test
      cannot be used. We describe a novel Winston-Lutz like mulitarget test (MTT) for
      verifying accurate positioning. METHODS: A target phantom, comprised of an
      acrylic plate with recesses for three 3/4" spheres was constructed and a high
      resolution (0.5*0.5*0.8 mm) CT scan obtained with PTFE spheres placed in the
      recesses. The scan was imported into a commercial treatment planning system and
      multiple beams were prepared, having their isocenter at the centroid of the
      arrangement of spheres. Every beam incorporated three MLC-defined rectangular
      apertures that circumscribed the spheres. Custom software selected setup
      parameters (table, gantry and collimator angle, MLC openings) such that the
      spheres were centered as precisely as possible within their respective MLC
      fields, considering the discrete width of collimator leaves. The phantom, with
      the PTFE replaced by steel spheres, was placed on the treatment couch and imaged
      using stereoscopic x-ray beams. A 6 degree-of-freedom robotic couch applied
      translations and rotations to reproduce the CT position. A MV EPID rendered
      images of the spheres within their respective apertures, allowing identification
      of sphere and aperture centers. Any error upstream would manifest itself as
      inaccurate centering of a sphere. RESULTS: Eight beams with table angle 0 and two
      beams each with table angles 49.7, 89.8, 272.3, and 310.1 were selected. The
      maximum calculated distance between any sphere and the respective aperture center
      was 0.07 mm. The median difference measured from the MV images ranged from 0.1 mm
      to 1.4 mm with a median of 0.8 mm. CONCLUSIONS: The MTT is a practical end-to-end
      test for quality assurance of the entire positioning process in multitarget
      radiosurgery, from CT scanning to beam delivery.

PMID- 28518538
TI  - How does the pattern of aeroallergen sensitization change over time across all
      ages?
AB  - BACKGROUND: Identification of aeroallergen sensitization is important for
      diagnosis and management of allergic diseases. Immunoglobulin E (IgE)
      sensitization status is known to change over time. However, few studies have
      explored changes in sensitization patterns across all age groups. The aim of the
      present study was to evaluate the changing patterns of in vitro IgE sensitization
      tests in allergic rhinitis patients across all age groups. METHODS: We recruited
      all patients who were diagnosed as having rhinitis and who underwent in vitro IgE
      sensitization testing from 2007 to 2016. Of these, we included 138 who underwent
      repeat testing. We analyzed epidemiological data and allergen sensitization
      patterns. RESULTS: Of all patients, 56.5% of exhibited changes in allergen
      sensitization patterns. The allergens to which all age groups were sensitive were
      most commonly mites, with the exception of patients aged 40 to 59 years. The age
      group in which "new sensitization," composed of those with "newly developed
      sensitization" and "sensitization to more allergens," was most frequent was the 2
      to 12 years old group, followed by the 20 to 39 years old group. The age group in
      which "desensitization," composed of those with "negative conversion" and
      "desensitization to fewer allergens," was most prevalent was the 20 to 39 years
      old group followed by the 13 to 19 years old group. Grass pollen was the most
      common newly-sensitized allergen and also the most common desensitized allergen.
      CONCLUSION: IgE sensitization to aeroallergens can change in individuals with
      allergy. These changes may be different according to the patient's age. If
      rhinitis symptoms or treatment efficacy changes, repeat IgE sensitization testing
      is needed to find changes in allergen sensitization patterns.

PMID- 28518658
TI  - TU-E-BRA-11: Volume of Interest Cone Beam CT with a Low-Z Linear Accelerator
      Target: Proof-of-Concept.
AB  - PURPOSE: This study demonstrates feasibility and advantages of volume of interest
      (VOI) cone beam CT (CBCT) imaging performed with an x-ray beam generated from
      2.35 MeV electrons incident on a carbon linear accelerator target. METHODS: The
      electron beam energy was reduced to 2.35 MeV in a Varian 21EX linear accelerator
      containing a 7.6 mm thick carbon x-ray target. Arbitrary imaging volumes were
      defined in the planning system to produce dynamic MLC sequences capable of
      tracking off-axis VOIs in phantoms. To reduce truncation artefacts, missing data
      in projection images were completed using a priori DRR information from the
      planning CT set. The feasibility of the approach was shown through imaging of an
      anthropomorphic phantom and the head-and-neck section of a lamb. TLD800 and EBT2
      radiochromic film measurements were used to compare the VOI dose distributions
      with those for full-field techniques. CNR was measured for VOIs ranging from 4 to
      15 cm diameter. RESULTS: The 2.35 MV/Carbon beam provides favorable CNR
      characteristics, although marked boundary and cupping artefacts arise due to
      truncation of projection data. These artefacts are largely eliminated using the
      DRR filling technique. Imaging dose was reduced by 5-10% and 75% inside and
      outside of the VOI, respectively, compared to full-field imaging for a cranial
      VOI. For the 2.35 MV/Carbon beam, CNR was shown to be approximately invariant
      with VOI dimension for bone and lung objects. This indicates that the advantage
      of the VOI approach with the low-Z target beam is substantial imaging dose
      reduction, not improvement of image quality. CONCLUSIONS: VOI CBCT using a 2.35
      MV/Carbon beam is a feasible technique whereby a chosen imaging volume can be
      defined in the planning system and tracked during acquisition. The novel x-ray
      beam affords good CNR characteristics while imaging dose is localized to the
      chosen VOI. Funding for this project has been received from Varian Medical,
      Incorporated.

PMID- 28518659
TI  - TU-C-218-01: Effective Medical Imaging Physics Education.
AB  - : A practical and applied knowledge of physics and the associated technology is
      required for the clinically effective and safe use of the various medical imaging
      modalities. This is needed by all involved in the imaging process, including
      radiologists, especially residents in training, technologists, and physicists who
      provide consultation on optimum and safe procedures and as educators for the
      other imaging professionals. This area of education is undergoing considerable
      change and evolution for three reasons: 1. Increasing capabilities and complexity
      of medical imaging technology and procedures, 2.Expanding scope and availability
      of educational resources, especially on the internet, and 3. A significant
      increase in our knowledge of the mental learning process and the design of
      learning activities to optimize effectiveness and efficiency, especially for
      clinically applied physics. This course will address those three issues by
      providing guidance on establishing appropriate clinically focused learning
      outcomes, a review of the brain function for enhancing clinically applied
      physics, and the design and delivery of effective learning activities beginning
      with the classroom and continuing through learning physics during the clinical
      practice of radiology. Characteristics of each type of learning activity will be
      considered with respect to effectiveness and efficiency in achieving appropriate
      learning outcomes. A variety of available resources will be identified and
      demonstrated for use in the different phases of learning process. A major focus
      is on enhancing the role of the medical physicist in clinical radiology both as a
      resource and educator with contemporary technology being the tool, but not the
      teacher. LEARNING OBJECTIVES: 1. Develop physics learning objectives that will
      support effective and safe medical imaging procedures. 2. Understand specific
      brain functions that are involved in learning and applying physics. 3. Describe
      the characteristics and development of mental knowledge structures for applied
      clinical physics. 4. List the established levels of learning and associate each
      with specific functions that can be performed. 5. Analyze the different types of
      learning activities (classroom, individual study, clinical, etc.) with respect to
      effectiveness and efficiency. 6. Design and Provide a comprehensive physics
      education program with each activity optimized with respect to outcomes and
      available resources.

PMID- 28518660
TI  - TU-E-217BCD-10: Dose Reduction in Digital Breast Tomosynthesis with the Dose
      Reduction Prior Image Constrained Compressed Sensing (DR-PICCS) Algorithm.
AB  - PURPOSE: To reduce image noise and radiation dose in Digital Breast Tomosynthesis
      (DBT) reconstructions. METHODS: A retrospective study was performed on clinical
      data sets acquired at a normal dose with Hologic Selenia Dimensions DBT systems.
      The Prior Image Constrained Compressed Sensing (PICCS) algorithm was used to
      reduce image noise. In addition, a prospective study was performed on an American
      College of Radiology breast phantom at various dose levels and the PICCS
      algorithm was used to reconstruct images at the corresponding radiation dose
      levels. The reconstructed images were inspected visually, and the noise levels in
      various regions of interest were quantitatively measured and compared between
      images. RESULTS: In the case of the clinical data, the PICCS reconstructions
      showed dramatic noise reduction (over 35%) with no loss of diagnostically
      important features such as calcifications or low contrast lesions; visibility of
      low contrast lesions was improved with PICCS. Dose reduction of 28% was possible
      with the phantom data, and the low dose PICCS reconstructions of phantom data
      show improved low contrast lesion detectability and lower noise. CONCLUSIONS: The
      work indicates potential dose savings in digital breast tomosynthesis. The
      diagnostic quality of the phantom reconstructions at 28% reduced dose was
      equivalent to or better than those acquired at full dose. The noise suppression
      in the clinical data sets improved visibility of low contrast lesions without
      sacrificing important diagnostic features. Support for this project was provided
      by a grant from Hologic Inc.

PMID- 28518661
TI  - TU-E-BRB-04: Adaptive Stereotactic-Body Radiation Therapy (SBRT) Planning for
      Lung Cancer.
AB  - PURPOSE: Tumor shrinkage during lung SBRT has been reported. Adaptive SBRT
      planning can potentially escalate dose to the target and mitigate dose to
      surrounding tissues. In this study, we investigated dosimetric effects of
      adaptive lung SBRT planning using cone-bean CT (CBCT) images. METHODS: 48
      patients who had SBRT treatments for lung cancer in our institution were included
      in this study. All patients underwent a 3D helical CT scan and 4DCT scan for
      treatment planning. Treatments were delivered on Linac machines equipped with kV
      OBI, CBCT, and MV EPID. CBCT images of all patients were retrospectively analyzed
      to determine tumor size changes. 10 patients with the largest percentages of
      tumor shrinkage were selected for adaptive planning. Plans were created on CBCT
      images of each fraction using the same planning parameters as the original CT
      based plans. ITV was contoured on CBCT. PTV was generated by adding 5 mm margin
      to ITV. Two accumulative dose plans, non-adaptive (P-NON) and adaptive (P-ADP),
      were determined for each patient using deformable image registration via Velocity
      AI. Dosimetric comparisons between PNON and PADP were performed for all OARs
      using RTOG0915 metrics. Statistical significances were tested using paired t-test
      with a significance level of 0.05. RESULTS: Comformality ranged from 1.03 to
      1.41, with small intra-subject variations (ranged from 0.01 to 0.06). Compared to
      PNON, PADP reduced all dosimetric metrics and significantly in the following (p
      value range: 0.02-0.04): V20Gy of lungs; D0.35cc, D1.2cc and maximum dose of
      cord, D5cc and maximum dose of esophagus, D30cc of chest wall, and D15cc of
      heart. Coverage to original GTV is comparable in two plans. CONCLUSIONS: Adaptive
      SBRT planning for selected patients resulted in significant dose reduction for
      adjacent OARs. It has the potential to further escalate dose to the target and
      mitigate dose to surrounding tissues.

PMID- 28518662
TI  - TU-G-BRCD-01: Will the High Cost of Proton Therapy Facilities Limit the
      Availability of Proton Therapy Treatment?
AB  - : The potential dose distribution advantages associated with proton therapy, and
      particularly with pencil beam scanning (PBS) techniques, have lead to
      considerable interest in this modality in recent years. However, the large
      capital expenditure necessary for such a project requires careful financial
      consideration and business planning. The complexity of the beam delivery systems
      impacts the capital expenditure and the PBS only systems presently being
      advocated can reduce these costs. Also several manufacturers are considering "one
      room" facilities as less expensive alternatives to multi-room facilities. This
      presentation includes a brief introduction to beam delivery options (passive
      scattering, uniform and modulated scanning) and some of the new technologies
      proposed for providing less expensive proton therapy systems. Based on current
      experience, data on proton therapy center start-up costs, running costs and the
      financial challenges associated with making this highly conformal therapy more
      widely available will be discussed. Issues associated with proton therapy
      implementation that are key to project success include strong project management,
      vendor cooperation and collaboration, staff recruitment and training. Time
      management during facility start up is a major concern, particularly in multi
      room systems, where time must be shared between continuing vendor system
      validation, verification and acceptance testing, and user commissioning and
      patient treatments. The challenges associated with facility operation during this
      period and beyond are discussed, focusing on how standardization of process,
      downtime and smart scheduling can influence operational efficiency. LEARNING
      OBJECTIVES: 1. To understand the available choices for proton therapy facilities,
      the different beam delivery systems and the financial implications associated
      with these choices. 2. To understand the key elements necessary for successfully
      implementing a proton therapy program. 3. To understand the challenges associated
      with on-going facility management to achieve an efficient fully operational
      system.

PMID- 28518663
TI  - TU-E-BRA-04: Real-Time Automatic Fiducial Marker Detection in Low Contrast Cine
      MV Images.
AB  - PURPOSE: Intrafraction motion tracking using beam-line MV images have gained much
      attention because no additional imaging dose is introduced. Since MV images have
      much lower contrast than kV images, a robust marker detection algorithm is a pre
      requisite. In this work, we develop a novel, fast, and robust method to detect
      implanted markers in low-contrast cine-MV patient images. METHODS: Several marker
      detection methods have been proposed in the recent years. These methods are all
      based on template matching or its derivatives. Template matching needs to match
      object shape that changes significantly for different implantation and projection
      angle. While these methods require a large number of templates to cover the
      different situations, they are often forced to use a smaller number of templates
      to reduce the computation load because their methods all require exhaustive
      search in the ROI. We solve this problem by synergetic use of modern but well
      tested computer vision and AI techniques - detect implanted markers utilizing
      discriminant analysis for initialization and mean-shift feature space analysis
      for sequential tracking. This novel approach avoids exhaustive search by
      exploiting the temporal correlation between consecutive frames and makes it
      possible to perform more sophisticated detection at the beginning to improve the
      accuracy, followed by ultrafast sequential tracking after the initialization. The
      method was evaluated using 1149 cine-MV images from 2 prostate IMRT patients and
      compared with manual marker detection results from 6 researchers. The average of
      the manual detection results is considered as the ground truth. RESULTS: The
      average RMS errors of the automatic tracking from the ground truth are 1.9 and
      2.1 pixels for the 2 patients (0.26mm/pixel). The standard deviations of the
      results from the 6 researchers are 2.3 and 2.6 pixels. CONCLUSION: The proposed
      method can achieve similar marker detection accuracy to manual detection in low
      contract cine-MV images.

PMID- 28518665
TI  - TU-E-211-01: Establishing Multidisciplinary Collaboration as a Medical Physicist.
AB  - : Many medical physicists are scientists at heart and their career fulfillment
      includes a balance of clinical service and research development.
      Multidisciplinary collaboration is a great way for the medical physicists to
      advance science and technology of our fields and the fields of our collaborators.
      Cross-pollination among scientists of different fields has been the key for some
      of the most significant breakthroughs in science and medicine and produced some
      of the most rewarding experiences for the individuals involved. However, medical
      physicists face unique challenges in establishing multidisciplinary collaboration
      because our time and resources for research are often quite limited compared to
      basic scientists. Yet we medical physicists are uniquely positioned and have a
      tremendous opportunity to create/contribute to multidisciplinary research: our
      fields are already multidisciplinary in nature and hospital environment is
      problem rich. How do we establish and carry out research collaboration with
      scientists of other fields? How to balance research with your higher priority
      clinical service? How do you find the right multidisciplinary collaboration in
      your own environment? We will discuss the challenges, provide real exemplary
      solutions to the above questions, and offer advise to medical physicists who are
      interested in starting or improving their multidisciplinary collaboration. There
      are different kinds of multidisciplinary collaborations a medical physicist can
      create and participate at different involvement levels. Multidisciplinary
      collaboration is not for every medical physicist but for those who seek and
      devote time to it, the experience can be truly rewarding and the impact can be
      enormous. LEARNING OBJECTIVES: 1. Learn the types of multidisciplinary
      collaboration medical physicists can created/participated 2. Learn the approaches
      and strategies to develop collaborations with scientists and professional of
      other fields3. Understand the challenges and different approaches to balance
      clinical service and multidisciplinary research collaboration.

PMID- 28518664
TI  - TU-E-217BCD-03: Characterization of Anatomical Noise in Mammography,
      Tomosynthesis and Breast CT.
AB  - PURPOSE: The role of breast density in cancer detection has been well
      characterized, and newer modalities such as breast tomosynthesis and breast CT
      (bCT) were developed to improve cancer detection in the dense breast by reducing
      anatomical complexity. Anatomical noise was characterized on a small cohort of
      patient images and compared across digital mammography, tomosynthesis, and bCT
      images. METHODS AND MATERIALS: An IRB-approved and HIPPA-compliant clinical study
      was performed on women undergoing breast biopsy, and mammography, tomosynthesis,
      and bCT were performed on both breasts immediately prior to biopsy. A total of 23
      women participated in this study, and the unaffected breast (no lesion) was
      evaluated. A total of 1000 regions of interest were sampled on each image data
      set, and the 2D noise power spectrum (NPS) was evaluated. This was radially
      averaged to produce a 1D NPS, and the NPS was fit to a power law: ln{NPS(f)} =
      alpha+betaxln(f), over an anatomically-relevant range of spatial frequencies. The
      slope, beta, was averaged across patients and compared between modalities and
      projections. RESULTS: The value of beta was determined for bCT data sets, and
      they were 1.75 (0.424), 1.83 (0.352), and 1.79 (0.397), for the coronal, sagittal
      and axial views, respectively. For tomosynthesis, beta was 3.06 (0.361) and 3.10
      (0.315) for the CC and MLO views, respectively. For mammography, these values
      were 3.17 (0.226) and 3.30 (0.236), for the CC and MLO views, respectively. The
      values of beta for breast CT were significantly different than those for
      tomosynthesis and mammography (p<0.001, all 12 comparisons). CONCLUSIONS: The
      results of this investigation demonstrate that the anatomical complexity of the
      breast, as characterized by the parameter beta, is statistically similar between
      mammography and tomosynthesis, a somewhat surprising finding. The breast CT image
      data, however, demonstrate a statistically-significant reduction in beta across
      all projections. Funded in part by Hologic Corporation and by a grant from the
      National Institute of Biomedical Imaging and Bioengineering, EB002138.

PMID- 28518666
TI  - TU-F-213AB-01: Diagnostic Workforce and Manpower Survey.
AB  - : Since AAPM Report No. 33 on Diagnostic Radiology Physics staffing is more than
      20 years old, the Diagnostic Work and Workforce Study Subcommittee (DWWSS) of the
      Professional Council was formed to conduct a new study and update the data. The
      intent of the DWWSS study has two goals. First, it wanted to assess the number of
      FTE diagnostic physicists needed to support the QC, acceptance tests, radiation
      safety and other clinical functions for various imaging modalities, such as: CT
      scanners, MRI units, angiography rooms, ultrasound units, nuclear medicine
      imagers and other equipment. For example, the preliminary results indicate that
      the median annual physics support for one CT scanner is 0.007 FTE or 12.6 hours
      per unit. Second, the study wanted to provide an estimate of the cost of these
      physics services in terms of a fraction of a dollar per patient examination
      performed. For example, the cost for physics support of CT would be $0.27 for
      each CT procedure. This information would be similar to the Abt study conducted
      in Radiation Oncology. Radiation therapy physicists have utilized the Abt studies
      to generate re-imbursement for physics services and to justify financially the
      cost of their work efforts. Appropriate recognition for physics efforts in
      Diagnostic Radiology has never been properly quantified nor appreciated. With all
      the current and future changes occurring in healthcare, the information from the
      DWWSS survey could be important to the future of diagnostic physicists. Although
      diagnostic physicists are involved with many other activities such as teaching of
      residents and research, information about the clinical equipment support effort
      could be used to assess diagnostic physics staffing needs. The goals of the DWWSS
      study and the preliminary findings will be presented. OBJECTIVE: 1. Present the
      goals of the DWWSS Diagnostic Physicist Survey.2. Present potential benefits to
      the AAPM members from this survey.3. Present findings from the preliminary
      analysis of the survey.

PMID- 28518668
TI  - TU-G-BRB-02: A New Mathematical Framework for IMRT Inverse Planning with Voxel
      Dependent Optimization Parameters.
AB  - PURPOSE: To establish a new mathematical framework for IMRT treatment
      optimization with voxel-dependent optimization parameters. METHODS: In IMRT
      inverse treatment planning, a physician seeks for a plan to deliver a prescribed
      dose to the target while sparing the nearby healthy tissues. The conflict between
      these objectives makes the multi-criteria optimization an appropriate tool.
      Traditionally, a clinically acceptable plan can be generated by fine-tuning organ
      based parameters. We establish a new mathematical framework by using voxel-based
      parameters for optimization. We introduce three different Pareto surfaces, prove
      the relationship between those surfaces, and compare voxel-based and organ-based
      methods. We prove some new theorems providing conditions under which the Pareto
      optimality is guaranteed. RESULTS: The new mathematical framework has shown that:
      1) Using an increasing voxel penalty function with an increasing derivative, in
      particular the popular power function, it is possible to explore the entire
      Pareto surface by changing voxel-based weighting factors, which increases the
      chances of getting more desirable plan. 2) The Pareto optimality is always
      guaranteed by adjusting voxel-based weighting factors. 3) If the plan is
      initially produced by adjusting organ-based weighting factors, it is impossible
      to improve all the DVH curves at the same time by adjusting voxel-based weighting
      factors. 4) A larger Pareto surface is explored by changing voxel-based weighting
      factors than by changing organ-based weighting factors, possibly leading to a
      plan with better trade-offs. 5) The Pareto optimality is not necessarily
      guaranteed while we are adjusting the voxel reference doses, and hence, adjusting
      voxel-based weighting factors is preferred in terms of preserving the Pareto
      optimality. CONCLUSIONS: We have developed a mathematical framework for IMRT
      optimization using voxel-based parameters. We can improve the plan quality by
      adjusting voxel-based weighting factors after organ-based parameter adjustment.
      This work is supported by Varian Medical Systems through a Master Research
      Agreement.

PMID- 28518667
TI  - TU-E-BRB-08: Dual Gated Volumetric Modulated Arc Therapy.
AB  - PURPOSE: Gated Volumetric Modulated Arc Therapy (VMAT) is an emerging treatment
      modality for Stereotactic Body Radiotherapy (SBRT). However, gating significantly
      prolongs treatment time. In order to enhance treatment efficiency, a novel dual
      gated VMAT, in which dynamic arc deliveries are executed sequentially in
      alternating exhale and inhale phases, is proposed and evaluated experimentally.
      METHODS: The essence of dual gated VMAT is to take advantage of the natural
      pauses that occur at inspiration and exhalation by alternatively delivering the
      dose at the two phases, instead of the exhale window only. The arc deliveries at
      the two phases are realized by rotating gantry forward at the exhale window and
      backward at the inhale in an alternative fashion. Custom XML scripts were
      developed in Varian's TrueBeam STx Developer Mode to enable dual gated VMAT
      delivery. RapidArc plans for a lung case were generated for both inhale and
      exhale phases. The two plans were then combined into a dual gated arc by
      interleaving the arc treatment nodes of the two RapidArc plans. The dual gated
      plan was delivered in the development mode of TrueBeam LINAC onto a motion
      phantom and the delivery was measured by using pinpoint chamber/film/diode array
      (delta 4). The measured dose distribution was compared with that computed using
      Eclipse AAA algorithm. The treatment delivery time was recorded and compared with
      the corresponding single gated plans. RESULTS: Relative to the corresponding
      single gated delivery, it was found that treatment time efficiency was improved
      by 95.5% for the case studied here. Pinpoint chamber absolute dose measurement
      agreed the calculation to within 0.7%. Diode chamber array measurements revealed
      that 97.5% of measurement points of dual gated RapidArc delivery passed the 3%
      and 3mm gamma-test criterion. CONCLUSIONS: A dual gated VMAT treatment has been
      developed and implemented successfully with nearly doubled treatment delivery
      efficiency.

PMID- 28518669
TI  - TU-E-BRA-08: A Comprehensive Study on the Relationship between Image Quality and
      Imaging Dose in Low-Dose Cone Beam CT.
AB  - PURPOSE: To investigate image quality as a function of number of projections and
      tube load per projection in compressive sensing (CS) based low-dose cone beam CT
      (CBCT), and achieve optimal low-dose scan protocols in image guided radiation
      therapy (IGRT). METHODS: We have performed CS-based CBCT reconstruction with
      different combinations of number of projections (from 46 to 364) and mAs (from
      0.2 to 2.4 mAs/view), which covers the whole clinically relevant range. Image
      quality is assessed in each case. On this basis, optimal scan protocols are
      analyzed according to various IGRT applications. RESULTS: Image quality degrades
      ~10% when the imaging dose decreases from 400 to 100 total mAs, further ~10% from
      100 to 40 total mAs, and another ~80% below 40 total mAs. Image quality on iso
      low-dose lines at 36.8, 72.6, 109.2 and 145.6 total mAs varies 17.16%, 13.69%,
      11.99% and 5.74% in terms RMSE with various scanning protocols. CONCLUSIONS: 1)
      In CS-based CBCT, image quality has little degradation with imaging dose> 100
      total mAs. Optimal low-dose scan protocols likely fall in the range of 40-100
      total mAs. 2) At a constant low-dose level, the scan protocol that with super
      sparse views (projection number < 50) is the most challenging case. 3) The
      optimal scan protocol is the combination of a medium number of projections and a
      medium level of mAs/view. This is more evident when the dose is ~72.8 total mAs
      or below, and when the ROI is a low-contrast or high-resolution object. 4) The
      clinically acceptable lowest imaging dose level is task dependent. In our study,
      72.8mAs is a safe dose level for visualizing low-contrast objects, while 12.2
      total mAs is sufficient for detecting high-contrast objects of diameter greater
      than 3 mm. This work is supported in part by NIH (1R01CA154747-01), Varian
      Medical Systems through a Master Research Agreement, and the Thrasher Research
      Fund.

PMID- 28518670
TI  - TU-E-217BCD-07: Pilot Study on Consistency in Size Metrics for a Multimodality
      PEM/MR Breast Imaging Approach.
AB  - PURPOSE: In this study, we evaluated the degree of consistency between size
      metrics obtained from PEM and MRI to determine the intrinsic effectiveness of a
      multimodality approach using these two systems for breast imaging. METHODS: Under
      an IRB-approved protocol, 42 cases were considered (16 patients with 28 lesions),
      each consisting of an MRI data set and corresponding PEM data set, with an
      inclusion criterion of being obtained within 2 weeks of each other. Lesions were
      delineated manually on the PEM images and semi-automatically on the MRI images
      for efficiency. In addition to volume, equivalent sphere diameter (ESD) was
      evaluated for each lesion. This metric describes the diameter of a sphere with
      the same volume as that of the lesion, and is useful for minimizing the cubic
      impact of a single voxel contribution inherent to volume calculations. RESULTS:
      The relationship between PEM based volumes and MRI based volumes showed a linear
      trend around VolMRI=VolPEM demonstrating a degree of consistency in the two
      volumes. The correlation between VolMRI and VolPEM was calculated as 0.547 with a
      corresponding p-value of 0.00018 demonstrating a significant correlation. The
      associated concordance was calculated as 0.534. The ESD metric showed a more
      significant linear trend with correlation 0.733 and corresponding p-value 3.5*10
      8, indicating consistency in lesion size. The concordance is 0.717, indicating
      high reproducibility. CONCLUSION: Multimodality PEM/MRI breast imaging has the
      potential to combine functional and molecular imaging information for a powerful
      tool in cancer staging and evaluation of response to therapy. The resulting,
      expanded data set is of use only if fundamental size metrics are consistent
      between the two modalities. Our pilot data demonstrates that size metrics as we
      extracted from the image data are consistent between PEM and MRI breast image
      sets.Maryellen Giger is a stockholder in R2 Technology/Hologic, has equity in
      Quantitative Insights, and receives royalties from Hologic, GE Medical Systems,
      MEDIAN Technologies, Riverain Medical, Mitsubishi and Toshiba. It is the
      University of Chicago Conflict of Interest Policy that investigators disclose
      publicly actual or potential significant financial interest that would reasonably
      appear to be directly and significantly affected by the research activities.

PMID- 28518671
TI  - TU-E-BRA-10: Personalized Utility Function for Radiotherapy Based on Pulmonary
      Ventilation of Locally Advanced Lung Cancer Patients.
AB  - PURPOSE: To develop tailor-made utility functions based on each patient's
      pulmonary function distribution so that personalized organ-function-based
      treatment plan is obtained for locally advanced lung cancer patients. METHODS:
      Five locally advanced lung cancer patients were retrospectively evaluated in the
      study. Fractional regional ventilation was obtained by performing subtraction of
      spatially matched and corrected 4DCT images. Histogram of the fraction
      ventilation values was generated for each patient. The cumulative distribution
      function (CDF), which represented an inverse relationship with the desired dose
      to each voxel for function preservation, showed potential as personalized utility
      function. In order to spare the majority of the volume with pulmonary function, a
      more aggressive utility function was defined as a piece-wise linear function
      based on the most frequent fractional ventilation value (peak of the histogram).
      This utility function was used in the objective function during treatment
      planning. Conventional objectives and constraints were maintained during the
      planning process. RESULTS: Both conventional plan and personalized functional
      plan were classified as satisfactory plans by physician based on conventional
      dose and dose-volume metrics. However, functional plan successfully spared high
      ventilation volume based on each patient's unique condition. When spatial
      function information was included to collect function dose/dose-volume metrics,
      significant reduction of fV20, fV30 and mean lung dose was achieved by function
      based personalized plan with p-value < 0.01. CONCLUSIONS: Organ-function-based
      radiotherapy has been presented to incorporate patient's pulmonary function in
      hopes of reducing the risk of complications. Current methods utilize the function
      information in the same fashion across patients. We took one step further to not
      only incorporate heterogeneous pulmonary function during treatment planning but
      also generate personalized utility function based on the function distribution of
      each patient. AAPM Research Seed Funding Initiative.

PMID- 28518672
TI  - TU-C-217A-01: The Joint Commission Sentinel Event Alert 47 - Impact and
      Experience.
AB  - On August 24, 2011 The Joint Commission (TJC) issued Sentinel Event Alert #47:
      Radiation Risks of Diagnostic Imaging. This document goes far beyond traditional
      state compliance and is based on sound concepts issued by FDA in 2010. It
      explores numerous means by which facilities can avoid patient harm from imaging
      procedures. TJC and state inspectors have begun to ask facilities how they have
      addressed these concerns. This presentation will explore the Sentinel Event Alert
      #47 document, and summarize the results of Audits performed to assess progress
      and identify areas for improvement.

PMID- 28518673
TI  - TU-E-217BCD-09: The Feasibility of the Dual-Dictionary Method for Breast Computed
      Tomography Based on Photon-Counting Detectors.
AB  - PURPOSE: To investigate the feasibility of an Iterative Reconstruction (IR)
      method utilizing the algebraic reconstruction technique coupled with dual
      dictionary learning for the application of dedicated breast computed tomography
      (CT) based on a photon-counting detector. METHODS: Postmortem breast samples were
      scanned in an experimental fan beam CT system based on a Cadmium-Zinc-Telluride
      (CZT) photon-counting detector. Images were reconstructed from various numbers of
      projections with both IR and Filtered-Back-Projection (FBP) methods. Contrast-to
      Noise Ratio (CNR) between the glandular and adipose tissue of postmortem breast
      samples were calculated to evaluate the quality of images reconstructed from IR
      and FBP. In addition to CNR, the spatial resolution was also used as a metric to
      evaluate the quality of images reconstructed from the two methods. This is
      further studied with a high-resolution phantom consisting of a 14 cm diameter, 10
      cm length polymethylmethacrylate (PMMA) cylinder. A 5 cm diameter coaxial volume
      of Interest insert that contains fine Aluminum wires of various diameters was
      used to determine spatial resolution. RESULTS: The spatial resolution and CNR
      were better when identical sinograms were reconstructed in IR as compared to FBP.
      In comparison with FBP reconstruction, a similar CNR was achieved using IR method
      with up to a factor of 5 fewer projections. CONCLUSIONS: The results of this
      study suggest that IR method can significantly reduce the required number of
      projections for a CT reconstruction compared to FBP method to achieve an
      equivalent CNR. Therefore, the scanning time of a CZT-based CT system using the
      IR method can potentially be reduced.

PMID- 28518674
TI  - TU-E-BRB-03: Biological Dose Optimization for SBRT of Lung Cancer: One Size Does
      Not Fit All.
AB  - PURPOSE: Given the differences in tumor size and location, encountered in lung
      SBRT, we hypothesize that 'one dose fractionation regimen does not fit all', i.e.
      that there is a role for patient-specific dose prescription based on optimization
      of biological models. METHODS: Sixty one NSCLC patients (tumor volume 46.5+/-47.3
      cc) treated with stereotactic body radiotherapy (48 Gy in 4fx) were
      retrospectively studied. Clinically treated plans were generated using Brainlab's
      Pencil Beam (PB-BL), and then recalculated with fixed MUs using Anisotropic
      Analytic Algorithm (AAA), Pencil Beam (PB-EC), Monte Carlo (MC) and Collapsed
      Cone-Convolution (CCC). DVHs were exported to calculate TCP (Poisson) and NTCP
      (Lyman-Kutcher-Burman). TCP/NTCP model parameters were utilized from published
      data. For each dose distribution two dose response curves were generated by
      scaling the prescription dose and assuming a linear relationship between the
      prescription dose and entire 3D dose distribution. In addition, associations were
      assessed between changes in each algorithm's TCP relative to PB-BL, target
      diameter, and local density (density of the 70% isodose covering the PTV).
      RESULTS: For PB-BL, mean TCP was 99.6%+/-0.9%, whereas for same MUs, mean TCP for
      PB-EC, AAA, CC and MC plans were 96.5+/-14.3%, 74.6+/-31.6%, 74.4+/-32.4% and
      76.8+/-32.0%, respectively. With the same prescription dose for all plans, TCP
      values changed to 98.1+/-8.7%, 96.5+/-15.3%, 77.5+/-28.6%, 85.4+/-25.8% and
      92.9+/-20.1% for PB-BL, PB-EC, AAA, and CCC, MC, respectively, indicating that
      AAA and CCC dose distributions are likely less homogeneous relative to MC. The
      TCP improvement was 12.3%, 8.9% and 4.4% for AAA, CCC and MC-based plans when the
      average NTCP before optimization was set as the upper limit for lung toxicity.
      CONCLUSIONS: This work supports patient-specific dose prescription strategies,
      based on biological optimization, for lung SBRT. However, further investigation
      is warranted. Acknowledgement: supported in part by a grant from Varian Medical
      Systems.

PMID- 28518675
TI  - TU-E-BRA-03: Real-Time Fiducial Detection and Prostate Movement Assessment with
      Cine MV Images in RapidArc Treatments.
AB  - PURPOSE: To develop an algorithm for detection of metallic fiducial markers in
      cine MV images, and to assess the prostate movement during RapidArc treatment.
      METHODS: A Varian TrueBeam linear accelerator (LINAC) was used to deliver
      RapidArc treatment for prostate patients. Cine images were acquired with the
      onboard electronic portal imaging device (EPID) using the MV therapeutic beam.
      Three metallic fiducial markers were implanted inside the prostate. To detect the
      fiducial position, we explicitly account for the possible marker blockage by MLC
      during beam modulation. If the marker is not blocked, we employ the planning
      coordinates of the marker centroids projected onto the cine MV images and perform
      template matching in the vicinity of its projection to localize the actual
      position of the marker. Displacements of the fiducial markers are assessed by
      comparing the actual and planned positions. RESULTS: We analyzed ~280 cine MV
      images acquired during a 55-sec RapidArc treatment for a prostate patient. The
      three markers were visible in about 46%, 52%, and 48% of the images, and at least
      one fiducial was visible during almost entire treatment (97% of the time). The
      marker detection algorithm agrees well with manual detection (< 0.2 mm). The mean
      displacement for each fiducial was 0.40 +/- 0.42, 0.27 +/- 0.29, and 0.46 +/-
      0.34 mm. The maximum displacement was 2.33, 1.75, and 2.23 mm. CONCLUSIONS: An
      algorithm for automatic detection of fiducial markers in cine MV images has been
      developed. The prostate movement during a RapidArc treatment has been analyzed
      for a patient with implanted markers. Accurate target positioning is achieved at
      all times during treatment. In light of the random nature of intrafraction
      prostate motion, this work represents an important step toward real-time image
      guided prostate radiation therapy.

PMID- 28518676
TI  - TU-E-217BCD-02: An X-Ray Scatter Correction Method for Dedicated Breast Computed
      Tomography.
AB  - PURPOSE: To reduce the impact of x-ray scatter in dedicated breast computed
      tomography (BCT) images. METHODS: The inclusion of x-ray scatter in BCT
      projections results in cupping artifacts, loss of contrast, and quantitative
      inaccuracies. To correct for this, an additional set of BCT projections is
      acquired with a tungsten plate placed between the x-ray source and the patient
      breast. The tungsten plate includes a two-dimensional grid of perforations to
      generate an array of pencil beams. Due to the limited area illuminated by the x
      ray pencil beams, an array of signals of primary x-rays only is obtained. At the
      pencil beam locations, the difference between the plate projections and the
      standard projections is an estimate of the scatter present in the latter. These
      estimates are interpolated to obtain scatter-only estimates of the whole images,
      which are subtracted from the standard projections, resulting in BCT projections
      with primary signal only, which are then reconstructed. To reduce the impact of
      the quantum noise of the scatter signal, the resulting reconstructions are noise
      filtered. Monte Carlo simulations were performed to estimate the amount of
      scatter included in the pencil beams and the dose from these additional
      projections. The algorithm was tested using breast phantoms on a BCT clinical
      prototype system. RESULTS: The maximum scatter signal in the pencil beams is 2.2%
      (mean of 0.7%) of the total signal, so the pencil beams are an excellent estimate
      of the primary-only signal. The additional projections Result in only 0.4% of the
      glandular dose of the standard projections. The homogeneity of the resulting
      phantom images, the signal difference between adipose and glandular tissue,
      reconstruction accuracy, and contrast-to-noise ratios were improved with this
      algorithm. CONCLUSIONS: The proposed algorithm has the potential to substantially
      improve BCT image quality with practically no additional dose to the patient
      breast.

PMID- 28518677
TI  - TU-D-217A-01: CTDI and Patient Dose: A European Perspective.
AB  - : Dose in CT has been a dominant topic in Medical Physics for at least a decade.
      This was for good reason since increasing use of CT necessarily led to an
      increase of cumulative dose to the population and inappropriate use of CT in some
      cases led to an unnecessarily high exposure of patients with subsequent coverage
      in the U.S. media. Fortunately, this situation also triggered a number of
      positive technical developments and fruitful initiatives worldwide. Currently,
      even "sub-mSv CT" is a realistic topic. However, we also engage in extensive
      discussions of the topic "CTDI and patient dose". They do not always seem to be
      pragmatic and sometimes are unnecessarily complicated. One reason may be that the
      topics computed tomography dose index (CTDI) and patient dose are seen
      necessarily combined. This lecture aims at discussing and hopefully helping to
      resolve some of the issues. Key points and suggestions are the following: * CTDI
      is a proven and reasonably good concept for scanner dosimetry and quality control
      (QC) on standard 64-row scanners. There is no major debate on CTDI efficiency and
      similar issues in Europe. * The new IEC scanner dosimetry concept to be used for
      wider detectors is acceptable; there is no need for new and heavy phantoms. *
      There still is a need of phantoms and concepts for QC of automated exposure
      control systems in CT. * CTDI should not and need not be changed and expanded to
      assess patient dose. * Patient dose estimates (both organ and effective dose) are
      based on air kerma measurements (without a CTDI phantom) and MC calculations
      using mathematical phantoms and/or voxel models. The DLP-to-E conversion which is
      accepted in Europe for more than a decade was based on this approach. * Patient
      dose estimates, both organ and effective dose, should be scanner- and patient
      specific. Fast MC programs and dose software allow for this. Manufacturer
      cooperation is a necessity, and there are first positive examples. * The concept
      of diagnostic reference levels (DRL) which was started in Europe in the 1990s and
      is in wide use today has to be revisited. It need not be based on CTDI further on
      but, for example, on a revised scanner- and patient-specific DLP-to-E conversion.
      * An international consensus on the topics CTDI and patient dose appears
      desirable. All these points do not mean a revolution but rather aim at staying
      with established equipment. The two major objectives are to * avoid unnecessary
      QC burden of medical physicists who are threatened with extended CTDI
      measurements * provide more reliable and understandable information regarding
      patient dose in real time. Organ dose and effective dose are preferable to DLP.
      LEARNING OBJECTIVES: 1. Understand that CTDI is a technical concept for scanner
      acceptance and constancy testing 2. Learn about concepts for patient- and scanner
      specific patient dose estimates 3. Learn about the concept of diagnostic
      reference levels and its strengths and weaknesses Research sponsored by Siemens
      Healthcare and by CT Imaging GmbH, both in Erlangen, Germany.

PMID- 28518678
TI  - TU-E-218-01: PET/CT QA/QC and Acceptance Testing.
AB  - : Combined PET/CT imaging has become a routine imaging technique in diagnostic
      radiology and nuclear medicine alike. In this regard a thorough understanding of
      this modality's quality assurance and control procedures including acceptance
      testing is a necessary pre-requisite to ensure the optimal performance of this
      imaging modality. This session is designed to explain the QA and QC procedures
      for a PET/CT scanner with examples from two different manufacturers. The session
      will also cover the frequency of these tests and the elements to implement a
      QA/QC program for PET/CT imaging. Finally the session will cover the NEMA
      standard for acceptance testing of PET scanners and their meanings as well as
      additional recommended tests for hybrid (PET/CT) systems. LEARNING OBJECTIVES: 1.
      Summarize the signal processing steps for coincidence detection 2. Understand the
      components of a daily QA procedure 3. Identify and trouble shoot possible sources
      of failure in daily QA 4. List the recommended frequency of QA/QC tests 5.
      Describe the process of scanner calibration 6. Name the different components of
      the NEMA test used for PET acceptance testing 7. Understand the meaning of the
      results of the NEMA tests.

PMID- 28518679
TI  - TU-E-BRB-07: An EPID Based Dosimetric Verification Tool for SBRT with High Dose
      Rate FFF Beams.
AB  - PURPOSE: The increasing use of unflattened high dose rate and/or small sized
      fields in stereotactic body radiosurgery (SBRT) presents a significant challenge
      and calls for new tools for dosimetric measurements and quality assurance (QA).
      The purpose of this work is to investigate a high spatial resolution (0.2mm) and
      high frame rate (50Hz) amorphous silicon flat-panel electronic portal imaging
      device (EPID) from Perkin Elmer for SBRT. METHODS: A Monte Carlo N-Particle
      eXtended (MCNPX) simulation and convolution based calibration procedure has been
      developed to derive a voxel-based response function specific to the EPID
      construct and beam characteristics. Both standard photon beams and flattening
      filter free (FFF) beams of all energies from Varian TrueBeam STX were studied and
      the linearity and dose rate dependence were tested. EPID with detailed materials
      composition was simulated using the MCNPX to generate a scatter kernel composed
      of dose deposition in the EPID phosphor, and optical photon spreading and to
      deconvolve the EPID images to high spatial resolution photon fluence map. The
      fluence map was convolved with MCNPX generated kernels to the 3D dose
      distribution in the phantom and compared with pinpoint ion chamber and film
      measurements. RESULTS: EPID response showed excellent linearity (R2>0.9998) and
      dose rate dependence less than 1.8% for up to 2400MU/min. Output factors for
      field sizes ranging from 1*1 to 20*20cm2 were measured and used to fit the
      optical photon glare kernel. Fluence profiles deconvolved using MCNPX scattering
      kernel agrees with the measurements to within 2%. Results of typical pre
      treatment QA test exhibit excellent spatial resolution required for SBRT.
      CONCLUSIONS: The high spatial resolution and high frame rate EPID proved to be an
      accurate and efficient tool for SBRT QA. Through convolution with MCNPX
      scattering core and comprehensive EPID calibration, accurate 3D dose maps can be
      generated for independent dosimetric verification of SBRT treatments.

PMID- 28518680
TI  - TU-G-BRB-01: Continuous Path Optimization for Non-Coplanar Variant SAD IMRT
      Delivery Using C-Arm Machines.
AB  - PURPOSE: To develop and investigate a continuous path optimization methodology to
      traverse prescribed non-coplanar IMRT beams with variant SADs, by orchestrating
      the couch and gantry movement with zero-collision, minimal patient motion
      consequence and machine travel time. METHODS: We convert the given collision zone
      definition and the prescribed beam location/angles to a tumor-centric coordinate,
      and represent the traversing path as a continuous open curve. We proceed to
      optimize a composite objective function consisting of (1) a strong attraction
      energy to ensure all prescribed beams are en-route, (2) a penalty for patient
      motion inducing couch motion, and (3) a penalty for travel-time inducing overall
      path-length. Feasibility manifold is defined as complement to collision zone and
      the optimization is performed with a level set representation evolved with
      variational flows. The proposed method has been implemented and tested on
      clinically derived data. In the absence of any existing solutions for the same
      problem, we validate by: (1) visual inspecting the generated path rendered in the
      3D tumor-centric coordinates, and (2) comparing with a traveling-salesman (TSP)
      solution obtained from relaxing the variant SADs and continuous collision
      avoidance requirement. RESULTS: The proposed method has generated delivery paths
      that are smooth and intuitively appealing. Under relaxed settings, our results
      outperform the generic TSP solutions and agree with specially tuned versions.
      CONCLUSIONS: We have proposed a novel systematic approach that automatically
      determines the continuous path to cover non-coplanar, varying SAD IMRT beams. The
      proposed approach accommodates patient-specific collision zone definition and
      ensures its avoidance continuously. The differential penalty to couch and gantry
      motions allows customizable tradeoff between patient geometry stability and
      delivery efficiency. This development paves the path to achieve safe, accurate
      and efficient non-coplanar IMRT delivery with the advanced robotic controls in
      new-generation C-arm systems, enabling practical harvesting of the dose benefit
      offered by non-coplanar, variant SAD IMRT treatment.

PMID- 28518681
TI  - TU-E-BRA-07: Post-Operative Eye Plaque Imaging Using Tomotherapy MVCT.
AB  - PURPOSE: Intra-operative ultrasound is used to verify the positioning of
      episcleral eye plaques used to treat ocular melanoma. Ultrasound can be ambiguous
      because of image artifacts, and plaques may shift position after surgery.
      Ultrasound verification is particularly challenging for anterior tumors. Post
      operative imaging could be used to trigger interventions that would prevent local
      treatment failure. We investigated if, and under what conditions, the Tomotherapy
      megavoltage computed tomography (MVCT) system could be used to perform post
      implantation verification of eye plaque positioning. METHODS: Plaques were placed
      on a preserved cow's eye, and imaged with the megavoltage CT of a Tomotherapy
      linear accelerator (Accuray, Sunnyvale, CA). The images were visually and
      quantitatively assessed to determine if they were of sufficient quality to verify
      tumor coverage and plaque tilt with respect to the sclera. We used the visibility
      of the lens as a proxy for visibility of a tumor. To test the utility of
      hypothetical higher beam current Tomotherapy images, we averaged sequential
      images of the same setup. RESULTS: The plaque, the lens of the eye, and the globe
      are visible in the images. The CNR of the lens with respect to the vitreous was
      5.6 for a single image. For 10 images averaged, the CNR was 9.2. Estimated dose
      from a single image was 1.3 cGy (body CTDIvol); even 10 times this dose would be
      an acceptable image-guidance dose for radiotherapy patients. One limitation of
      the imaging procedure is the long scan time (up to 240 seconds), during which
      time any significant patient motion would lead to image artifacts. Human trials
      on eye plaque patients are planned. CONCLUSIONS: Tomotherapy MVCT imaging could
      be used to verify tumor coverage and plaque tilt after episcleral plaque
      implantation. Tumors should be visible in standard Tomotherapy images but higher
      beam current images would be preferred if available.

PMID- 28518682
TI  - TU-E-217BCD-06: Cone Beam Breast CT with a High Resolution Flat Panel Detector
      Improvement of Calcification Visibility.
AB  - PURPOSE: To investigate the advantage of a high resolution flat panel detector
      for improving the visibility of microcalcifications (MCs) in cone beam breast CT
      Methods: A paraffin cylinder was used to simulate a 100% adipose breast. Calcium
      carbonate grains, ranging from 125-140 MUm to 224 - 250 MUm in size, were used to
      simulate the MCs. Groups of 25 same size MCs were embedded at the phantom center.
      The phantom was scanned with a bench-top CBCT system at various exposure levels.
      A 75MUm pitch flat panel detector (Dexela 2923, Perkin Elmer) with 500MUm thick
      CsI scintillator plate was used as the high resolution detector. A 194 MUm pitch
      detector (Paxscan 4030CB, Varian Medical Systems) was used for reference. 300
      projection images were acquired over 360 degrees  and reconstructed. The images
      were reviewed by 6 readers. The MC visibility was quantified as the fraction of
      visible MCs and averaged for comparison. The visibility was plotted as a function
      of the estimated dose level for various MC sizes and detectors. The MTFs and DQEs
      were measured and compared. RESULTS: For imaging small (200 MUm and smaller) MCs,
      the visibility achieved with the 75MUm pitch detector was found to be
      significantly higher than those achieved with the 194MUm pitch detector. For
      imaging larger MCs, there was little advantage in using the 75MUm pitch detector.
      Using the 75MUm pitch detector, MCs as small as 180 MUm could be imaged to
      achieve a visibility of 78% with an isocenter tissue dose of ~20 mGys versus 62%
      achieved with the 194 MUm pitch detector at the same dose level. CONCLUSIONS: It
      was found that a high pitch flat panel detector had the advantages of extending
      its imaging capability to higher frequencies thus helping improve the visibility
      when used to image small MCs. This work was supported in part by grants CA104759,
      CA13852 and CA124585 from NIH-NCI, a grant EB00117 from NIH-NIBIB, and a
      subcontract from NIST-ATP.

PMID- 28518683
TI  - TU-E-BRCD-01: The Emerging Role of Image-Guidance for Breast Radiotherapy.
AB  - : Breast radiotherapy has undergone significant innovation in the past 10 years
      and the frequency of image-guided radiation therapy (IGRT) is increasing. This
      session will review clinical indications for breast radiotherapy (RT) and
      conventional RT methods. Ongoing clinical innovations in breast RT techniques
      will then be highlighted (e.g., partial breast irradiation, IMRT and VMAT for
      irradiation of the internal mammary chain). Finally, the emerging role of IGRT
      will be discussed with its application to improving setup reproducibility and
      designing appropriate target margins. The IGRT methods will include surface
      imaging although the focus will remain on more widely-available IGRT systems such
      as CBCT and kV imaging. a.Brief clinical review of RT as a function of breast
      cancer stage according to RTOG guidelines b.Dosimetric advances in breast RT,
      including IMRT and VMAT for nodal irradiation and partial breast irradiation for
      early-stage cancer c.The role of IGRT for setup reproducibility and margin design
      d. IGRT for adaptive RT in cases of seroma reduction. LEARNING OBJECTIVES: 1.
      Review the clinical targets for breast RT as a function of cancer stage 2. Learn
      about innovative uses of advanced radiotherapy techniques for breast treatment 3.
      Highlight the emerging role of IGRT to guide planning and treatment. Jan-Jakob
      Sonke's research is sponsored by Elekta Corporation.

PMID- 28518684
TI  - TU-G-211-01: New Member Symposium.
AB  - As a new member of the AAPM, it's easy to feel overwhelmed by the size and
      complexity of the association and to be unaware of the benefits and opportunities
      available to members. At this year's AAPM national meeting in Charlotte, we will
      host a New Member Symposium, where you can learn more about the organization,
      member resources, opportunities to get involved, and about topics of particular
      interest to new professionals. We encourage you to take advantage of this great
      opportunity to learn valuable information and to grow your professional network.
      Following an introduction from Dr. Gary A. Ezzell, the AAPM President; Michael
      Woodward of the AAPM staff will provide a crash course on the AAPM structure and
      organization, as well as some pointers on navigating the website. Next will be
      Dr. Michael Mills presenting on the current state of the U.S. Medical Physics
      Workforce, Staffing, Supply & Demand, and Limited Residency slots. Registered
      attendees will receive a raffle ticket for entry in a drawing to win a
      complimentary registration for the 2013 Annual Meeting in Indianapolis. In
      addition, all new members who register for the Symposium will receive a drink
      ticket good for one complimentary beer served after the New Member Symposium
      during the social with committee chairs from 4 AAPM Councils: Science, Education,
      Professional, and Administrative.

PMID- 28518685
TI  - TU-E-217BCD-08: Extraction and Insertion of Tumor Masses in Cone Beam Breast CT
      Images.
AB  - PURPOSE: To develop and validate algorithms for extraction and insertion of three
      dimensional (3D) profiles of tumor masses in cone beam breast CT (CBBCT) images
      to create simulated abnormality for evaluation with observer performance study.
      METHODS: A bench-top experimental CBBCT scanner was constructed and used to image
      mastectomy breast specimens with IRB approval. 5 sets of CBBCT images with
      confirmed tumor masses and 2 sets of normal CBBCT images were selected and used
      for this study. All CBBCT images were first corrected for cupping artifacts. The
      corrected images were then processed to reduce their noise levels and form the
      denoised images. The corrected and denoised CBBCT images for normal breasts were
      then segmented into adipose and glandular voxels. The images for abnormal breasts
      were reviewed by mammographers with the help of clinical images and reports to
      delineate the tumor masses and form 3D tumor maps. Using these maps, the 3D tumor
      profiles were rescaled to average glandular signals around the insertion
      locations in normal images. The boundaries of the 3D rescaled tumor profiles were
      smoothed to avoid sharp edge. The resultant 3D tumor profiles were inserted onto
      cupping artifact corrected normal CBBCT images by replacing the signals in
      adipose voxels near the insertion locations. The cupping artifacts were then
      added back to generate the simulated abnormal CBBCT images. These images were
      then visually compared with actual abnormal images for their degree of realism.
      RESULTS: Based on visual comparison, the simulated abnormal CBBCT images showed
      no significant difference in realism from actual abnormal CBBCT images.
      CONCLUSIONS: We have successfully demonstrated the technique to extract 3D tumor
      profiles from abnormal CBBCT images and insert them onto normal CBBCT images to
      form simulated abnormal images for use in observer performance study. This work
      was supported in part by grants CA104759, CA13852 and CA124585 from the NIH-NCI,
      a research grant EB00117 from the NIH-NIBIB, and a subcontract from NIST-ATP.

PMID- 28518686
TI  - TU-E-BRB-02: A Decision Support Tool for SBRT Planning Using a Searchable DVH
      Database.
AB  - PURPOSE: Develop a decision support tool that aids dosimetrists, physicians, and
      physicists in assessing and improving plan quality through comparison to plans
      previously used in similar clinical situations. METHODS: Software was developed
      to capture and store DVHs and other clinically relevant treatment plan
      characteristics in a database. In addition to the plan DVH, the database contains
      a total of 24 plan characteristics including fractionation, prescribed dose,
      treatment volume, prior surgery, tumor position, and smoking history. DVH and
      other plan data was captured from the treatment planning system via exported
      dicom RT files. Structures in the plan were automatically matched by name to a
      list of standard structures using a system of regular expressions. Additional
      fields were entered manually using a simple java interface. As a support tool, a
      plan under development can be quickly compared to similar plans in the database
      based on selected plan characteristics. A plot displaying the current and
      historical DVHs provides an easy visual comparison. Our interface also provides
      statistics for comparison for each dose/volume level such as average, minimum,
      maximum and standard deviation. RESULTS: DVHs from 111 lung SBRT plans treated
      from 2009-2011 were imported in accordance with an approved IRB protocol. As an
      example of data comparisons that can be easily performed to guide plan
      evaluation, we examined plans prescribing 5400cGy in 3 fractions and found that
      tumors >7.5cc (n=34) had an average PTV coverage of 94.2% (range: 73.5-95.0%),
      and tumors =7.5cc (n=35) had an average PTV coverage of 94.9% (range: 81.6
      99.6%). CONCLUSION: A searchable DVH database was constructed to provide
      planners, physicists, and physicians with a straightforward means of comparing
      plans against historic distributions of DVHs. In the future, outcome data will be
      included in the database to strengthen its functionality as a decision support
      and research tool.

PMID- 28518687
TI  - TU-G-213AB-02: Time-Space Compression for Fun and Profit: How to Do More, in Less
      Time, Without the Stress and Mess.
AB  - : "Time-space compression" means "processes that ... revolutionize the objective
      qualities of space and time." (David Harvey, The Condition of
      Postmodernity.)Modern workflows suffer from negative time-space compression:
      computers, internet, email, smartphones, texting and chat all promise
      productivity, yet they can encroach on our time and clutter our minds without
      eliminating those lurking piles of paper. Physicists in medicine face additional
      technology-related challenges on top of all that. However, the laws governing our
      time, workspaces, and teams are universal. Understand those laws, and you
      understand how to control the forces that derail personal and team workflow.
      Then, by drawing on a few practical techniques, you can create positive time
      space compression: revolutionizing your workspace and systems to get more done,
      with noticeably less stress, balancing work and fun in all your life areas,
      keeping your desk so clean your associates will think you're going on vacation.
      An approach called Total, Relaxed Organization (TRO) makes this possible. TRO was
      developed by Priacta, Inc. (Kevin Crenshaw's company) using best practices from
      many popular time management systems. TRO has measurable Results: an average net
      gain of 581 productive hrs/yr, and average stress reduction of 59.6% from all
      sources combined. While these numbers are subjective and self-reported, they
      indicate a consistent improvement in the quality of life for TRO adherents. This
      working presentation compresses a (normally paid) 7-hour TRO personal coaching
      session into a 75-minute interactive, entertaining, and highly-practical workshop
      for each participant. LEARNING OBJECTIVES: 1. Understand the key principles/laws
      that govern your use of time and (work)space. 2. Identify your personal barriers
      that currently work against those principles. 3. Create a personal action plan
      (based on those time/workspace principles and practical techniques) to re
      engineer your personal and team workflow for optimal results.

PMID- 28518688
TI  - TU-E-BRA-02: A Method to Remove Support Arm Backscatter from EPID Images.
AB  - PURPOSE: To develop a method for removing the effect of support arm backscatter
      from Varian electronic portal imaging devices (EPIDs), improving the dosimetric
      abilities of the imager. METHODS: A physical, kernel based model of the
      backscatter signal produced during an exposure was developed. The model
      parameters were determined through an optimization process, comparing measured
      images without arm backscatter (EPID removed from arm) to measured images that
      include arm backscatter. The backscatter model was used to develop a backscatter
      correction process that removes the support arm backscatter from measured EPID
      images. The correction process was tested by applying the method to measured
      images of 17 rectangular asymmetric fields and comparing the Result to off-arm
      images. The same process was repeated with 42 IMRT fields. RESULTS: The
      backscatter removal process was able to effectively remove the arm backscatter
      from all of the measured images and accurately predict the measured off-arm
      images. Comparing the corrected images to the measured off-arm images, the mean
      absolute difference at the centre of each rectangular field was 0.29% (standard
      deviation 0.18%). This is an improvement over the uncorrected images which gave a
      mean difference of 1.01% (standard deviation 0.73%). The largest discrepancy
      observed with the corrected images was 0.6%, compared to 2.8% for the uncorrected
      images. Comparing the corrected IMRT images to the measured off-arm images, an
      overall mean gamma value of 0.28 (standard deviation 0.04) was found using 2%,
      2mm criteria. Comparison of the uncorrected images to the measured off-arm images
      resulted in an overall mean gamma of 0.40 (standard deviation 0.10). CONCLUSIONS:
      A method for accurately and reliably removing the effect of support arm
      backscatter from EPID images has been developed and extensively tested. The
      method can be applied to any measured EPID image and does not require any
      additional information about the exposure.

PMID- 28518689
TI  - TU-E-217BCD-01: X-Ray Spectra for Breast CT.
AB  - PURPOSE: To study a range of x-ray spectra with regard to their suitability for
      dedicated breast CT, taking into account realistic tube loading limitations.
      METHODS: A simple theoretical model was used to get a preliminary indication of
      the best mono-energetic x-ray energy as a function of object size. That model was
      extended to poly-energetic spectra and used to study a range of object sizes,
      tube voltages, filter materials, and filter thicknesses. Spectra from IPEM Report
      78 were used as input to the model. Initially we have looked at lanthanide
      filters (Z = 57-60) and tube voltages from 30 to 80 kVp. Outputs from the model
      included contrast, contrast-to-noise ratio (CNR), dose, dose efficiency
      (CNR2/dose), and tube loading. Dose was estimated as incident minus transmitted
      energy fluence. We have also started experiments to verify the computational
      results. Experiments are done using a bench-top cone beam CT and a 14 cm diameter
      cylindrical PMMA phantom filled with liquid mixtures equivalent to breast tissue
      of varying glandularity. We use reconstructed data to determine the CNR of a test
      block representing 100% glandular breast tissue, immersed in the liquid. Air
      kerma measurements are obtained at the center and periphery of the phantom, and
      used in the calculation of dose efficiency. Monte Carlo calculations are being
      done to get a more accurate dose estimate. RESULTS: For a constant CNR,
      computational results indicate that as filter thickness increases above 0.4 mm
      dose efficiency plateaus. However, the power required to maintain a constant CNR
      becomes prohibitively large for filter thicknesses greater than 0.3 mm.
      CONCLUSIONS: Spectra generated at tube voltages above 40 kVp are likely to
      provide the best trade-off between dose efficiency and tube loading. For
      lanthanide filters, there is little benefit from using thicknesses greater than
      0.3 mm.

PMID- 28518690
TI  - TU-D-213AB-01: How You Can Be the Speaker and Communicator Everyone Wants You to
      Be.
AB  - Effectiveness of an oral presentation depends on the ability of the speaker to
      communicate with the audience. An important part of this communication is
      focusing on two to five key points and emphasizing those points during the
      presentation. Every aspect of the presentation should be purposeful and directed
      at facilitating learners' achievement of the objectives. This necessitates that
      the speaker has carefully developed the objectives and built the presentation
      around attainment of the objectives. A presentation should be designed to include
      as much audience participation as possible, no matter the size of the audience.
      Techniques to encourage audience participation include questioning,
      brainstorming, small-group activities, role-playing, case-based examples,
      directed listening, and use of an audience response system. It is first necessary
      to motivate and gain attention of the learner for learning to take place. This
      can be accomplished through appropriate use of humor, anecdotes, and quotations.
      This course will review adult learning principles and effective presentation
      skills, Learning Objectives: 1. Apply adult learning principles. 2. Demonstrate
      effective presentations skills.

PMID- 28518691
TI  - TU-E-217A-01: Informatics 1: DICOM and the QMP, Assessment of Color Displays.
AB  - : All Medical Physicists work with the DICOM Standard every day. But the
      involvement of Medical Physicists in the development of the Standard has been
      limited. Recently the DICOM Standards Committee (DSC) has established a new Dicom
      Working Group on Physics (i.e. WG28) and the AAPM has become the secretariat for
      WG28 and a voting member of the DSC. The structure and processes involved with
      making the DICOM Standard will be reviewed and the specific role DICOM WG28 has
      will be summarized. LEARNING OBJECTIVES: 1. Understand the processes involved
      with development of the DICOM Standard. 2. Learn how any Medical Physicist can
      become involved in the process of developing the DICOM Standard 3. Learn the
      charge and structure of WG28 and their current Work Items. Medical color monitors
      are now widely used for Diagnostic Radiology interpretations. Business class
      monitors are otherwise used for medical image presentation in clinical
      departments. Both the AAPM and IEC are now developing recommendations and
      standards for color monitor performance assessment in medicine. The basic
      principles of color vision and metrology will be reviewed and current progress
      with AAPM and IEC working groups will be summarized. LEARNING OBJECTIVES: 1.
      Understand the tristimulus model for human color vision. 2. Understand the ICC
      color management framework. 3. Understand the ICC color management framework. 4.
      Learn how to make color measurements. 5. Learn new recommendations for color
      white point specification.

PMID- 28518692
TI  - TU-E-BRB-06: Best in Physics (Therapy) - Development and Experimental Validation
      of EPID-Based 4D Dose Reconstruction.
AB  - PURPOSE: To develop and validate an EPID-based 4D patient dose reconstruction
      framework accounting for linac delivery uncertainties, interfractional and
      intrafractional motions, and interplay effect. METHODS: Patients with fiducial
      markers were scanned with 4D-CT for SBRT planning. Before treatment, in-room 4D
      CT was performed. Both the MLC and the tumor movements were tracked by
      continuously acquiring EPID images during treatment. Instead of directly using
      the heterogeneous transit photon fluence measured by the EPID, this method
      reconstructed the incident beam fluence based on the MLC apertures measured by
      the EPID and the delivered MU recorded by the linac. To account for the time
      dependent-geometry, the incident fluence distributions were sorted into their
      corresponding phases based on the tumor motion pattern detected by the EPID and
      accumulated as the incident fluence map for each phase. Together with 4D-CT, it
      was then used for Monte Carlo dose calculation. Deformable registration was
      performed to sum up the phase doses for treatment assessment. The feasibility of
      using the transit EPID images for incident fluence reconstruction was evaluated
      against EPID in-air measurements. The accuracy of 3D- and 4D-dose reconstruction
      was validated by a motordriven cylindrical diode array for six clinical SBRT
      plans. RESULTS: The average difference between the measured and reconstructed
      fluence maps is within 0.16%. The reconstructed 3D-dose shows 1.4% agreement in
      the CAX-dose and >98.5% gamma-passing-rate (2%/2mm) in the peripheral-dose. A
      distorted dose distribution is observed in the measurement for the moving
      ArcCheck-phantom. The comparison between the measured and the reconstructed 4D
      dose without considering interplay fails the gammaevaluation (59%-88.9% gamma
      passing-rate). In contrast, when the interplay is considered, the dose distortion
      phenomena is successfully represented in the reconstructed dose (>97.6% gamma
      passing-rate). CONCLUSIONS: The experimental validation demonstrates that the
      proposed method provides a practical way to reconstruct the fractional 4D-doses
      received by the patient and enables adaptive SBRT strategy.

PMID- 28518693
TI  - TU-G-BRCD-03: Managing Patient and Organ Motion in Proton Therapy.
AB  - BACKGROUND: The advent of proton based therapy has provided excitement in the
      radiation oncology community. Not in the least due to the theoretically
      advantageous geometrical properties of the dose deposition by such charged
      particles. In this presentation I will discuss the some of the challenges, which
      can make this tool sub-optimal when used in clinical practice with actual
      patients. METHODOLOGY: Data and analysis on patient setup variations and organ
      movement, gathered from "classical" photon therapy is projected to this new
      modality. Inter and intra fractional movement will be covered as well as the
      notion of margin determination in order to provide adequate coverage and in what
      way this makes sense. In addition, the time frame with which these uncertainties
      occur implies that different measures need to be taken and the use of in room
      imaging might be needed. Further, the advent of scanning techniques again provide
      an advantage as well as a disadvantage as far as movement is concerned.
      CONCLUSIONS: Proton therapy is a promising technique and exciting on a clinical
      and scientific level. In order to show significant improvement, knowledge with
      regard to targfet determination, as well as positioning is more critical in
      comparison with the classical modalities. LEARNING OBJECTIVES: 1. Knowledge on
      patient and/or organ movements motion effects. 2. Categorizing the movement in
      time and space. 3. Reflections on the impact of movement on proton based
      treatments.

PMID- 28518694
TI  - TU-E-BRA-06: Evaluation of a New MV X-Ray Detector Designed for the
      TomoTherapy(r) System.
AB  - PURPOSE: To evaluate the performance of a new MV X-ray detector prototype
      specifically designed for use on the TomoTherapy(r) System. METHODS: A gas-filled
      detector array, similar in concept to existing TomoTherapy detector arrays, has
      been designed and fabricated for the TomoTherapy System. Unlike existing detector
      arrays, the prototype detector array has a radius of curvature that matches the
      source-to-detector distance. Also, the internal structure of the detector such as
      the septa material and geometry has been optimized for MV X-rays. The prototype
      detector performance was assessed by measuring the signal properties of each of
      the detector channel signals. Signal, noise, and signal-to-noise ratios (SNR)
      were measured. Finally, the resulting MVCT image quality was assessed. RESULTS:
      The signal profile across the prototype detector more closely matches the
      incident X-ray beam intensity and, in particular, is missing the characteristic
      trough in the center of signal profiles from existing TomoTherapy detector
      arrays. Compared to an existing detector, the mean signal is approximately equal
      outside the central region. Inside the 100 central channels (out of 576 total
      channels), the prototype detector signal is substantially larger than the
      existing detector. The variation in the pulse-to-pulse signal (noise), after
      accounting for output fluctuations, is substantially lower with the new detector.
      The resulting SNR is an average of 18% higher across all channels, with an
      improvement of up to 36% for the central channels. The prototype detector yielded
      MVCT images that, compared to one typical system with an existing detector array,
      had 7% lower image noise in the periphery and 36% lower noise at the center of
      the image. CONCLUSIONS: This evaluation indicates that the performance of a new
      MV X-ray detector array prototype exceeds the performance of an existing detector
      array in terms of signal-to-noise ratio and resulting MVCT image quality.

PMID- 28518696
TI  - TU-E-213AB-02: The Regulatory Path to Achieve QMP Requirement.
AB  - : Licensure for medical physicists has been pursued for a number of years, with
      success in some states and failure in others. Lessons from these cases has been
      used to strengthen the licensure effort, but they have also demonstrated that
      licensure may not be an option in some states. In such cases, we still need a
      methodology to achieve credentialing and practice standards. A comprehensive
      registration approach may provide that methodology. This talk will discuss
      features of comprehensive registration, along with positive and negative aspects
      of the approach. It will be demonstrated that comprehensive registration is a
      viable alternative that can be used when licensure is not achievable. LEARNING
      OBJECTIVES: 1. Understand the differences between licensure and the regulatory
      approach. 2. Learn how the regulatory approach can achieve the goal of requiring
      se of Qualified Medical Physicists with an appropriate scope of practice. 3.
      Discuss ways of working with regulators to implement regulatory changes. 4.
      Discuss potential draft regulatory language.

PMID- 28518695
TI  - TU-E-217BCD-05: Dedicated Breast CT: Skin Thickness Measurements in a Diagnostic
      Population.
AB  - PURPOSE: To test the hypothesis that the mean skin thickness determined using
      cone-beam dedicated breast CT varied between breasts with malignant, hyperplasia
      and benign pathology, and to determine the appropriate skin thickness for Monte
      Carlo based estimation of normalized glandular dose coefficients. METHODS: Breast
      skin thickness was estimated in 137 women scheduled for biopsy (BI-RADS 4 or 5),
      who underwent unilateral cone-beam dedicated CT of the breast to be biopsied,
      after providing written informed consent and in adherence to an IRB-approved
      protocol. Pathology results were available for 132 women and there were 38
      malignancies. A previously reported method [Huang et al., Med Phys 35(4): 1199
      206, 2008] was applied to coronal (transverse) images reconstructed to 0.273 mm
      voxel size. The accuracy of the method was determined by imaging two phantoms of
      differing wall thickness and shape. For each breast, the mean, intra-breast
      standard deviation (SD) and the median skin thickness were computed. The mean
      skin thickness and associated confidence intervals (CI) in our study population
      were obtained from the mean skin thickness of each breast. RESULTS: The estimated
      mean wall thicknesses for both phantoms were within +/-1% of the measured
      thickness. At the 0.05 level (ANOVA), the skin thickness means did not vary
      significantly with pathology (p=0.61). For each breast, the median, mean and
      intra-breast SD, in mm, were in the range [0.87,2.23], [0.87,2.34], and
      [0.22,0.85], respectively. From all 137 women, the mean +/- inter-breast SD and
      95% CI were 1.44+/-0.25 and [1.40,1.48], respectively. CONCLUSIONS: The skin
      thickness means were not different between breasts with malignant and non
      malignant pathology. Our estimate of mean skin thickness is in agreement with a
      previous report. Skin thickness of approximately 1.45 mm, rather than the
      standard 4 mm [Wu et al., Radiology 193:83-9, 1994], is appropriate for Monte
      Carlo based determination of normalized glandular dose coefficients. Supported in
      part by the National Institutes of Health (NIH) grants R01 CA128906 and R21
      CA134129. The contents are solely the responsibility of the authors and do not
      represent the official views of the NIH or NCI.

PMID- 28518697
TI  - TU-F-217A-01: Informatics 2: Dose Monitoring.
AB  - : Public concern over radiation from medical imaging is now higher than ever
      before and hospitals are being placed under increased scrutiny to ensure that
      their patients do not receive radiation overdoses. California already requires
      that there is a record of a dose estimate for every CT examination. In response,
      there has been a renewed interest in research and commercial ventures for the
      best method to monitor radiation dose for medical imaging procedures. The goal of
      this session is to highlight some tools that are currently available for dose
      monitoring, to illustrate how using these tools can improve the quality of care
      at an institution, and to provide a sample of the future developments in
      radiation dose monitoring. LEARNING OBJECTIVES: 1. To provide an understanding of
      the basic science behind dose monitoring 2. To demonstrate few clinical
      implementation of dose monitoring systems 3. To discuss the advanced concepts
      currently under investigation (eg, patient size tracking) 4. To demonstrate how
      dose monitoring systems can be used for improved quality initiatives.

PMID- 28518698
TI  - TU-E-BRB-10: Dosimetric Consequences of Setup Errors Using CBCT for SBRT
      Localization.
AB  - PURPOSE: Steep dose gradients and high dose per fraction in stereotactic ablative
      radiation therapy (SABR or SBRT) necessitate highly accurate tumor localization.
      This study evaluates inter-fraction shifts, as defined by couch correction
      analysis, and investigates the effect of tumor location and internal target
      volume (ITV) on these shifts. In addition, residual errors associated with post
      CBCT correction and their dosimetric consequences were quantified. METHODS: Daily
      free-breathing (FB) CBCT images used for daily localization of 78 patients with
      non-small cell lung cancer were retrospectively evaluated. Among the population,
      39 patients also received pre-treatment kV images after CBCT alignment. ITV inter
      fraction displacement was evaluated by matching the CBCT and the FB helical CT
      images, and setup errors were quantified using orthogonal kV images. Associations
      between ITV location and inter-fraction motion were studied by categorizing
      tumors into the following locations: chest-wall seated (CWS) and island,
      peripheral, central, or upper, middle and lower. Dosimetric consequences for the
      patient with the largest setup error were explored. RESULTS: ITV inter-fraction
      motion included the mean of the systematic error, ?inter=(-1.4, 2.0, 1.6) mm,
      standard deviation (SD) of the systematic error, Sigmainter=(2.1, 4.2, 2.9) mm,
      and SD of random errors, sinter=(2.2, 3.2, 3.6) mm. No significant associations
      were observed between inter-fraction shifts and tumor location or volume. Using
      CBCT for image guidance reduced the observed errors to MUsetup=(-0.3, 0.1, 0.0)
      mm, Sigmasetup=(0.6, 0.6, 0.4) mm and ssetup=(1.2, 0.7, 0.7) mm. Dosimetric
      consequences for the patient with the largest setup error were explored. It was
      shown that a 3.0 mm setup margin was sufficient to provide greater than 95% dose
      coverage to the ITV. CONCLUSION: CBCT image guidance reduced setup errors
      significantly such that 2-3 mm, population-based, setup margins provided proper
      dose coverage to the ITV. Further investigation of inter-and intrafraction error
      classification by tumor location is warranted.

PMID- 28518699
TI  - TU-G-BRB-04: A Robust-CVaR Optimization Approach to Left-Sided Breast IMRT.
AB  - PURPOSE: To test the feasibility of a cardiac sparing IMRT planning approach for
      patients with left-sided breast cancer using a robust optimization model.
      METHODS: A robust optimization model was developed for breast IMRT. The concept
      of conditional-value-at-risk (CVaR) was used in the robust framework to guarantee
      that the clinical dose volume criteria for targets and organs at risk hold under
      uncertainty in the patient's breathing pattern. Clinical treatment methods for
      breast cancer (inhale breath-hold with active breathing control (ABC) or free
      breathing) were simulated via optimization models. A 4DCT patient dataset with
      target and organs at risk on each breathing phase was used to simulate a clinical
      case with a total of 20% increase in lung volume from exhale to inhale over 5
      phases. The results of the proposed robust model were compared with those of the
      current clinical models. RESULTS: Compared to the conventional IMRT method for
      breast cancer (with free breathing), the proposed robust-CVaR model resulted in a
      14.6% reduction in mean heart dose without compromising the target coverage and
      dose homogeneity. The clinical dose-volume limits for the heart as well as the
      clinical target volume were met in robust results. The robust method resulted in
      23.9% improvement in the maximum dose to 25cc of the heart volume. The robust
      results showed very low variability among the quality of planning and realized
      treatments. CONCLUSIONS: Using CVaR limits in a robust optimization framework can
      help improve the quality of IMRT treatments. The robust-CVaR can generate a high
      quality treatment plans, but is delivered during free breathing and does not
      require patient compliance with an external device. The quality of robust
      treatment remains the same under irregular breathing. Explicitly including
      metrics for lung and bigger motion amplitudes in the robust optimization method
      may further improve the results.

PMID- 28518701
TI  - TU-G-213AB-01: Organization and Productivity Strategies for Practicing Medical
      Physicists.
AB  - : Medical physicists face numerous challenges that create stress in the
      professional workplace. The modern work environment contains multiple
      communications channels, such as email, smart phones, text and instant messaging,
      voice mail, pagers, and more. These media make it difficult to organize incoming
      information, set priorities, and move important work forward in the face of rapid
      change and the requirement to fulfill multiple responsibilities. Medical
      physicists in particular are likely to feel acute stress due to off-peak work
      hour requirements, varied responsibilities including clinical duties, research,
      teaching, and regulatory matters, and the complexity of supervising other staff
      members. Many medical physicists also work in multiple physical locations, adding
      complexity to the task of organizing information and resources. Another common
      difficulty is that medical physicists' responsibilities typically include some
      duties that render them subject to frequent and urgent interruption, such as
      emergency response coverage for radiation safety. The real challenges in the
      current medical physics work environment differ from those encountered while
      taking courses and conducting research, as well as from earlier periods when
      medical physicists faced fewer varied responsibilities, slower-paced change, or
      both. Today's practicing physicist can benefit greatly from developing a formal
      framework and skill set to manage their personal workflow. This greatly increases
      the individual's effectiveness and reduces feelings of stress, while improving
      the effectiveness of teams or groups in which they participate. In this session,
      participants will learn about a number of techniques and strategies to manage
      their own personal workflow. Examples familiar to the medical physicist will be
      provided to illustrate methods to capture, organize, and act on important
      information, to delegate effectively, and to handle inevitable interruptions.
      LEARNING OBJECTIVES: 1. Describe the use of a personal workflow in managing
      ongoing or routine clinical physics duties. 2. Select an appropriate method for
      filing various documents and records commonly encountered in medical physics. 3.
      Implement strategies for minimizing the impact of interruptions on the
      physicist's daily work.

PMID- 28518700
TI  - TU-E-BRB-01: Similar-Case-Based Optimization of Beam Arrangements in Stereotactic
      Body Radiation Therapy.
AB  - PURPOSE: The quality of a treatment plan for stereotactic body radiotherapy
      (SBRT) depends on an experience of each treatment planner. Therefore, the
      treatment plans are subjectively determined by comparison of several treatment
      plans developed by time consuming iterative manners, while considering the
      benefit to a tumor and the risk to the surrounding normal tissues. The aim of our
      study was to develop an automated optimization method for beam arrangements based
      on similar cases in a database including plans designed by senior experienced
      treatment planners. METHODS: Our proposed method consists of three steps. First,
      similar cases were automatically selected based on image features from the
      treatment planning point of view. We defined four types of image features
      relevant to planning target volume (PTV) location, PTV shape, lung size, and
      spinal cord positional features. Second, the beam angles of the similar case were
      registered to the objective case with respect to lung regions using a linear
      registration technique. Third, the beam direction of the objective case was
      locally optimized based on the cost function considering radiation absorption in
      normal tissues and organs at risk. The proposed method was evaluated with 10 test
      cases and a treatment planning database including 81 cases by using eight
      planning evaluation indices such as D95, lung V20, and maximum spinal cord dose.
      RESULTS: The proposed method may provide usable beam directions, which have no
      statistically significant differences with the original beam directions (P >
      0.05) in terms of the seven planning evaluation indices. Moreover, the mean value
      of D95 for 10 test cases was improved with a statistically significant difference
      by using the proposed method, compared with the original beam directions (P =
      0.03). CONCLUSIONS: The proposed method could be used as a computer-assisted
      treatment planning tool for determination of beam directions in SBRT.

PMID- 28518702
TI  - TU-E-BRA-01: A Comparison of Various Online Strategies to Account for
      Interfractional Variations for Pancreatic Cancer.
AB  - PURPOSE: To indentify effective methods to address the large interfractional
      variations for pancreas irradiation, we compared various used/proposed online
      strategies. METHODS: The daily CTs acquired using a respiration-gated in-room CT
      for 9 pancreatic cancer patients treated with IGRT (i.e., online repositioning
      based on rigid-body alignment) were analyzed. The contours of the pancreas and
      duodenum on each daily CT set were generated by populating those from the
      planning CT using a deformable registration tool (ABAS, Elekta) with manual
      editing. PTV was generated with 3 mm margin. Nine online strategies were
      considered: 1) IGRT with 0 mm additional margin (AM), 2) IGRT with 2mm AM, 3)
      IGRT with 5mm AM, 4) IGRT with plan renormalized to maintain 95% PTV coverage, 5)
      Full scale reoptimization, 6) Reoptimization starting from the original plan, 7)
      Segment Aperture Morphing (SAM) from the original plan based on PTV shape change
      8) SAM plus Segment Weight Optimization (SWO), 9) Reoptimization starting from
      the SAM plan. One way ANOVA (analysis of variance) was applied to plan qualities
      for the 9 strategies to assess statistical significance in difference. RESULTS:
      The standard IGRT strategies (1-3) resulted in either inadequate PTV coverage or
      higher duodenum doses. Margin expansion along is not efficient to account for the
      changes. Full-scale reoptimization resulted in the best plan but requiring
      delineation of several structures. Reoptimization on top of available plan
      (strategies 6 and 9) was considerably faster. SAM strategy (7) is the fastest
      online replanning, as it requires only one structure (target) delineation, and
      it's plan quality was comparable to that for the full-scale reoptimization.
      CONCLUSION: Online replanning strategies can lead to either reduced duodenum dose
      or improved target coverage as compared to the current practice of IGRT. The SAM
      based online replanning is comparable to the full scale reoptimization and is
      efficient for practical use.

PMID- 28518703
TI  - TU-E-213CD-01: Image Guided Adaptive Brachytherapy for Cervical Cancer.
AB  - : Image-guidance plays an important role in modern radiation therapy,
      predominantly in external beam planning and delivery. In contrast, brachytherapy
      is still largely based on systems originally developed in the early 20th century.
      In recent years, with the advent of high/pulsed dose rate (HDR/PDR) afterloading
      technology, advanced treatment planning systems and CT and MRI compatible
      applicators, image-guided adaptive brachytherapy treatments are now achievable.
      With image guidance, the target can be delineated more precisely, resulting in
      delivering more controlled doses of radiation to the target while sparing
      surrounding healthy tissue. GEC-ESTRO guidelines are crucial for implementing
      robust and standardized image guided adaptive brachytherapy (IGABT). They rely on
      MRI-guided planning for cervical cancer. MRI can be performed for each
      brachytherapy (BT) fraction to adaptively plan and deliver the desired radiation
      dose with less toxicity to surrounding tissues. MR imaging has its advantages,
      but also challenges and limitations (image artifacts and distortion related to
      magnetic nonlinearity, MR sequence selection, accuracy of 3D applicator
      reconstruction) that need addressed. Moreover, MRI technology is not readily
      available in most Radiation Oncology departments, making its implementation hard.
      In such settings, CT or US-based planning can be used despite lacking the desired
      soft tissue resolution to accurately depict the target. Hybrid approaches have
      been proposed, where a first BT fraction is planed based on MRI, and subsequent
      fractions are performed with CT-guidance. Moreover, new
      intracavitary/interstitial applicators are becoming available and data from
      centers using existent applicators is maturing. Regardless of the type of
      adaptive image guided and applicators used, there are still ongoing debates
      regarding the prescription, the relevance of point A dose, treatment planning in
      general, and the use of inverse planning in particular, role of model-based dose
      calculation algorithms, adaptive strategies, intrafraction variability, in-vivo
      dosimetry, dose summation with external beam treatments, to mention just some of
      the challenges raised by implementing this treatment technique. This symposium is
      proposing to address all of these issues and update the community at large on the
      status of image guided adaptive brachytherapy for cervical cancer. LEARNING
      OBJECTIVES: 1. To discuss the physics perspective of role of IGABT in management
      of cervical cancer. 2. To compare IGABT approaches: MRI, CT, US, and Hybrid 3. To
      present the advantages, challenges, and limitations of MRI for IGABT. 4. To
      discuss hot topics in IGABT including planning strategies, role of model-based
      dose calculation algorithms, new applicators, dose specification.

PMID- 28518704
TI  - TU-C-218-02: Effective Oncology Physics Education.
AB  - : The education of medical physicists has historically been quite varied and
      medical physicists have entered the field through several pathways including
      specialized educational programs, postdoctoral fellowships, and on-the-job
      training. It is argued that the contributions of viewpoints from different
      branches of physics has contributed to the development of novel solutions and
      advances in radiation oncology. However, there also has been an effort recently
      to make graduate education of medical physicists more consistent and uniform,
      particularly for the preparation of clinically oriented therapy physicists. The
      trend towards a more systematic approach has been guided in part by the
      requirements for graduate program accreditation developed by CAMPEP and by the
      requirements for medical physicist certification by the ABR. At the same time,
      there has been criticism of this approach as being too confining and guiding
      graduates toward a career as technicians rather than independent thinkers.
      Educational programs have had to balance the requirements of accreditation and
      certification against the goal of preparing students for careers as independent
      researchers. Three speakers will describe the approaches taken by their graduate
      educational programs to meet the requirements of CAMPEP and adequately prepare
      graduates for certification by the ABR, while maintaining a commitment to
      providing a comprehensive education in medical physics. LEARNING OBJECTIVES: 1.
      Understand the requirements for graduate program accreditation 2. Understand the
      education and experience requirements for certification 3. Learn the approaches
      taken by several graduate programs to meet the requirements for accreditation and
      certification while providing a comprehensive education in medical physics.

PMID- 28518705
TI  - TU-E-217BCD-11: Evaluating the Performance of a Stationary Digital Breast
      Tomosynthesis System.
AB  - PURPOSE: In conventional Digital Breast Tomosynthesis (DBT) systems a single x
      ray source moves over a limited angle arc. This leads to motion blurring in the
      projection images associated with x-ray source motion and total scan times. We
      have developed a stationary DBT (s-DBT) system which forgoes a rotating source
      for an array of carbon nanotube (CNT) based x-ray sources. Here we report the
      results of evaluating the performance and the optimization of image acquisition
      parameters of the s-DBT system. METHODS: The s-DBT system consists of a linear
      source array with 31 x-ray generating focal spots distributed over a 30 degree
      angular span. The source array has been retrofitted onto a Hologic Selenia
      Dimensions DBT system. An American College of Radiology accreditation phantom was
      imaged to assess the quality of the reconstruction images in different
      configurations. A line wire phantom is used to measure the modulation transfer
      function (MTF). RESULTS: For the standard imaging protocol, the system resolution
      along the scanning direction is increased from 3.0 cycles/mm in DBT to 4.2
      cycles/mm in s-DBT at a magnification factor of 1.08. The MTF did not have a
      noticeable change between different configurations, whereas in DBT the MTF can be
      degraded for larger angular spans due to faster x-ray source motion. The overall
      image quality factor is found to be best for the configuration with a large
      angular span and intermittent number of projection views. CONCLUSIONS: We
      demonstrated successful construction and operation of the s-DBT system
      integrating a CNT x-ray source array with a Hologic DBT system. The spatial
      resolution of the s-DBT system is demonstrated to be substantially increased over
      the corresponding DBT system. It was found that a configuration with a large
      angular span, an intermittent number of projection views, and an even dose
      distribution resulted in the best overall image quality. Hologic INC has provided
      the Hologic Selenia Dimensions used in the research. The project is supported by
      the National Cancer Institute under grant number U54CA119343 and R01CA134598 and
      the UNC University Cancer Research Fund. Dr. Xin Qian is supported by a
      fellowship from the Department of Defense under grant number BC087505.

PMID- 28518706
TI  - TU-E-BRB-05: Impact of Interfractional Tumor Motion on Respiratory Gated
      Stereotactic Body Radiation Therapy for Lung Tumors.
AB  - PURPOSE: To investigate the impact of interfractional tumor motion on dose
      delivery of gated lung SBRT. METHODS: 4DCT scan for five lung patient was
      performed without breathing control at simulation and prior to each treatment.
      Gated treatment plans were performed on the end-exhale (50% phase) simulation CT
      with a 30% duty cycle. ITV was created by combining the GTVs at 40%, 50% and 60%
      phases. PTV was created by adding a 5 mm uniform margin to the ITV. All plans
      were normalized such that 60 Gy (3 fractions) was prescribed to the 85% isodose
      line. To calculate the accumulated dose over the treatment course, the original
      plan parameters were copied to the 40%, 50% and 60% CTs obtained prior to each
      treatment. In order to eliminate the effect of setup error to dose delivery,
      treatment isocenters at each fraction were determined by aligning the tumors on
      the slow CTs obtained prior to each treatment to that on the slow simulation CT.
      Doses recalculated on the 40% and 60% CTs at each fraction were warped through
      deformable CT image registration to their corresponding 50% CT to compose the 4D
      dose at that fraction. Those fractional 4D doses were warped to the 50%
      simulation CT to compose the accumulated 4D dose over the treatment course.
      RESULTS: The minimum tumor doses over the treatment course were 59.9, 45.1, 68.9,
      41.9 and 47.8 Gy respectively. Tumor V60s were 99.7, 92.2, 100, 97.2 and 93.0%
      respectively. The corresponding mean lung doses were 3.8, 6.4, 3.7, 4.4 and 3.7
      Gy respectively. CONCLUSIONS: Change in tumor motion pattern over the treatment
      course results in tumor underdosing. Tight margins are normally used in lung
      SBRT. Therefore monitoring of the reproducibility of interfractional tumor motion
      is critical to the success of dose delivery.

PMID- 28518707
TI  - TU-G-BRCD-02: Do Uncertainties in Proton Therapy Limit Its Clinical Potential?
AB  - PURPOSE: To discuss uncertainties in proton therapy and to outline how these
      might impact the widespread use of proton therapy. METHOD AND MATERIALS: This
      presentation will outline some of the differences in treatment planning for
      proton therapy as compared to photon therapy, in particularly related to the
      finite range of proton beams. The source of range uncertainties (e.g. dose
      calculation and treatment delivery) and some methods to address them will be
      presented. As examples we will discuss uncertainties in dose calculation in
      highly heterogeneous media (head and neck). Examples for in-vivo dose
      verification using dosimetric and imaging techniques in proton therapy will be
      outlined. Planning strategies to address uncertainties will be presented.
      Uncertainties due to the difference in biological effectiveness between proton
      and photon therapy will be addressed briefly. RESULTS: The difference in physics
      between photon and proton interactions causes proton therapy to be associated
      with different type of uncertainties than photon therapy. These affect treatment
      planning decisions and can influence whether proton therapy does show a
      significant clinical advantage. Theoretical advantages in proton dose
      distributions as compared to photon therapy do not necessarily translate in
      clinical gains. Exceptions are, for example, pediatric patients where the
      reduction in integral dose causes significant improvements in treatment outcome
      as compared to conventional radiation Conclusions: Proton therapy is being used
      increasingly in radiation therapy. Due to inherent uncertainties in proton
      therapy delivery, its full potential advantage cannot yet be reached for all
      sites. Proton therapy personnel needs to be aware of the subtleties of proton
      therapy. LEARNING OBJECTIVES: 1. To understand how treatment planning decisions
      in proton therapy differs from photon therapy 2. To understand the source and the
      magnitude of proton range uncertainties 3. To understand how uncertainties in
      proton therapy affect the acceptance and spread of this modality.

PMID- 28518708
TI  - TU-E-BRA-05: Reverse Geometry Imaging with MV Detector for Improved Image
      Resolution.
AB  - PURPOSE: Thick pixilated scintillators can offer significant improvements in
      quantum efficiency over phosphor screen megavoltage (MV) detectors. However
      spatial resolution can be compromised due to the spreading of light across pixels
      within septa. Of particular interest are the lower energy x-ray photons and
      associated light photons that produce higher image contrast but are stopped near
      the scintillator entrance surface. They suffer the most scattering in the
      scintillator prior to detection in the photodiodes. Reversing the detector
      geometry, so that the incident x-ray beam passes through the photodiode array
      into the scintillator, allows the light to scatter less prior to detection. This
      also reduces the Swank noise since now higher and lower energy x-ray photons tend
      to produce similar electronic signals. In this work, we present simulations and
      measurements of detector MTF for the conventional/forward and reverse geometries
      to demonstrate this phenomenon. METHODS: A tabletop system consisting of a Varian
      CX1 1MeV linear accelerator and a modified Varian Paxscan4030 with the readout
      electronics moved away from the incident the beam was used. A special holder was
      used to press a 2.5W*5.0L*2.0Hcm3 pixellated Cesium Iodide (CsI:Tl) scintillator
      array on to the detector glass. The CsI array had a pitch of 0.784mm with plastic
      septa between pixels and the photodiode array pitch was 0.192 mm. The MTF in the
      forward and reverse geometries was measured using a 0.5mm thick Tantalum slanted
      edge. Geant4-based Monte Carlo simulations were performed for comparison.
      RESULTS: The measured and simulated MTFs matched to within 3.4(+/-3.7)% in the
      forward and 4.4(+/-1.5)% in reverse geometries. The reverse geometry MTF was
      higher than the forward geometry MTF at all spatial frequencies and doubled to
      .25 at 0.3lp/mm. CONCLUSIONS: A novel method of improving the image resolution at
      MV energies was demonstrated. The improvements should be more pronounced with
      increased scintillator thickness. Funding support provided by NIH (grant number
      NIH R01 CA138426).

PMID- 28518709
TI  - TU-E-217BCD-04: Spectral Breast CT: Effect of Adaptive Filtration on CT Numbers,
      CT Noise, and CNR.
AB  - PURPOSE: Photon counting spectral breast CT is feasible in part due to using an
      adaptive filter. An adaptive filter provides flat x-ray intensity profile and
      constant x-ray energy spectrum across detector surface, decreases required
      detector count rate, and eliminates beam hardening artifacts. However, the
      altered x-ray exposure profiles at the breast and detector surface may influence
      the distribution of CT noise, CT numbers, and contrast to noise ratio (CNR)
      across the CT images. The purpose of this work was to investigate these effects.
      METHODS: Images of a CT phantom with and without adaptive filter were simulated
      at 60kVp, 90kVp, and 120kVp tube voltages and 660 mR total skin exposure. The CT
      phantom with water content had 14cm diameter, contrast elements representing
      adipose tissue and 2.5mg/cc iodine contrast located at 1cm, 3.5cm, and 6cm from
      center of the phantom. The CT numbers, CT noise, and CNR were measured at
      multiple locations for several filter/exposure combinations: (1)without adaptive
      filter for 660mR skin exposure; (2)with adaptive filter for 660mR skin exposure
      along central axis (mean skin exposure across the breast was <660mR); and (3)with
      adaptive filter for scaled exposure (mean skin exposure was 660mR). RESULTS: Beam
      hardening (cupping) artifacts had 47HU magnitude without adaptive filter but were
      eliminated with adaptive filter. CNR of contrast elements was comparable for (1)
      and (2) over central parts but was higher by 20-30% for (1) near the edge of the
      phantom. CNR was higher by 20-30% in (3) as compared to (2) over central parts
      and comparable near the edges. CONCLUSIONS: The adaptive filter provided: uniform
      distribution of CT noise, CNR, and CT numbers across CT images; comparable or
      better CNR with no dose penalty to the breast; and eliminated beam hardening
      artifacts.

PMID- 28518710
TI  - TU-E-213AB-01: JMPSLC Has Morphed into Medical Physics Licensure and Regulatory
      Recognition Subcommittee.
AB  - Based on direction from AAM Board of Directors, JMPLSC has redefined its scope
      and name. On November 4, 2011 the subcommittee renamed itself the Medical Physics
      Licensure and Regulatory Recognition Subcommittee. Its newly defined charge is to
      promote the protection of the public through the recognition of the profession of
      medical physics by legislation or regulation. The following pathways shall be
      implemented. 1. Recognition of the profession of medical physics through
      licensure by legislation: a. Support the formation and activities of state
      committee focused on professional licensure b. Provide model legislation c.
      Provide consultation on regulatory language to implement professional licensure
      2. Recognition of the profession of medical physics through regulation. a.
      Support the formation and activities of state committee focused on the regulatory
      approach b. Provide model regulation c. Provide consultation on regulatory
      language to implement professional licensure d. Collaborate with the CRCPD
      Subcommittee 3. Annually prepare status of subcommittees' activities. This
      presentation will describe recent efforts of the subcommittee and report on its
      successes, challenges and works in progress.

PMID- 28518711
TI  - TU-F-BRCD-01: Tolerance Levels and Methodologies for IMRT Verification QA.
AB  - : Intensity modulated radiation therapy (IMRT) is a technology intensive
      treatment modality involving the delivery of highly conformal dose distributions
      to patients. IMRT is becoming a standard of care for many disease sites and
      approximately 30%-60% of cancer patients in the United States receive IMRT
      treatments. Given the complexity of the IMRT treatment planning and delivery
      processes, a number of AAPM reports and guidance documents addressed the
      technical aspects of IMRT, including the need for comprehensive acceptance
      testing, commissioning, and QA programs for IMRT planning and delivery equipment.
      The implementation of these verification programs is essential to ensure the
      accuracy of IMRT delivery. Despite the critical role of patient-specific IMRT
      verification QA to ensure the safe delivery of IMRT treatments to patients as
      planned, there is little systematic guidance on the type of methodologies, tools,
      and acceptable tolerance levels that are needed in clinical practice.
      Furthermore, there are limited discussion on the pros and cons of the different
      delivery methods for QA measurements, and no recommendations on how to assess the
      clinical relevance of failed IMRT plans. LEARNING OBJECTIVES: 1. To discuss
      commonly employed IMRT measurement methods and discuss the pros and cons of each
      method. 2. To review methodologies for absolute dose verification (single small
      volume, 1D, 2D methods), and review dose-difference, DTA, and Gamma analysis
      techniques including the variability of vendors implementation 3. To review IMRT
      QA passing rates for given tolerances and action levels, and discuss the clinical
      relevance of failed IMRT QA.

PMID- 28518712
TI  - TU-E-BRB-09: Validation of Multi-Focal Stereotactic Radiosurgery with Volumetric
      Modulated Arc Therapy with High-Resolution 3D Dosimetry.
AB  - PURPOSE: Volumetric modulated arc therapy (VMAT) enables stereotactic
      radiosurgery (SRS) treatment for multiple lesions with a single isocenter setup.
      Dosimetry verification is highly challenging however, and the purpose of this
      study is to validate this new treatment using novel 3D dosimetry techniques, with
      potential for dramatically more comprehensive verification than possible with
      conventional approaches. METHODS: A cylindrical PRESAGE dosimeter was inserted
      into an RPC type head phantom for treatment validation. The phantom was
      immobilized with an SRS U-frame system and a set of simulation CT images was
      acquired with a SRS localizer. A 5-arc VMAT multi-focal SRS plan was created to
      treat 5 intracranial lesions simultaneously. A set of cone-beam CT (CBCT) images
      was then acquired to localize the isocenter, and the VMAT plan delivered to the
      combined phantom. The PRESAGE dosimeter was then removed and scanned by optical
      computed-tomography (optical-CT). The 3D PRESAGE dose measurement was
      reconstructed with 1 mm resolution. Another PRESAGE insert with a pre-drilled ion
      chamber channel was placed in the phantom and an SRS ion chamber was mounted for
      an absolute dose measurement. The phantom was again localized with CBCT and the
      VMAT plan was delivered. The dose measured with the ion chamber was compared with
      calculated dose. RESULTS: The mean planned and PRESAGE measured doses to target 1
      were 12.1Gy and 12.2 Gy, 18.7 Gy and 18.5 Gy for target 2, 18.6 Gy and 18.4 Gy
      for target 3, 15.5 Gy and 15.4 Gy for target 4, 18.7 Gy and 19.0 Gy for target 5.
      The 3D gamma passing rate was 95.6% for 3% and 1mm. The ion chamber measured dose
      was within 1% of the planned dose. CONCLUSIONS: Our 3D PRESAGE dose measurement
      shows that multi-focal VMAT is a valid technique for single isocenter SRS
      treatment of multiple lesions. This research is partially supported by NCI
      R01CA100835. This research is partially supported by NCI R01CA100835.

PMID- 28518713
TI  - TU-G-BRB-03: Iterative Optimization of Normalized Transmission Maps for IMRT
      Using Arbitrary Beam Profiles.
AB  - PURPOSE: Newly available flattening filter free (FFF) beam increases the dose
      rate by 3~6 times at the central axis. In reality, even flattening filtered beam
      is not perfectly flat. In addition, the beam profiles across different fields may
      not have the same amplitude. The existing inverse planning formalism based on the
      total-variation of intensity (or fluence) map cannot consider these properties of
      beam profiles. The purpose of this work is to develop a novel dose optimization
      scheme with incorporation of the inherent beam profiles to maximally utilize the
      efficacy of arbitrary beam profiles while preserving the convexity of the
      optimization problem. METHODS: To increase the accuracy of the problem formalism,
      we decompose the fluence map as an elementwise multiplication of the inherent
      beam profile and a normalized transmission map (NTM). Instead of attempting to
      optimize the fluence maps directly, we optimize the NTMs and beam profiles
      separately. A least-squares problem constrained by total-variation of NTMs is
      developed to derive the optimal fluence maps that balances the dose conformality
      and FFF beam delivery efficiency. With the resultant NTMs, we find beam profiles
      to renormalized NTMs. The proposed method iteratively optimizes and renormalizes
      NTMs in a closed loop manner. RESULTS: The advantage of the proposed method is
      demonstrated by using a head-neck case with flat beam profiles and a prostate
      case with non-flat beam profiles. The obtained NTMs achieve more conformal dose
      distribution while preserving piecewise constancy compared to the existing
      solution. CONCLUSIONS: The proposed formalism has two major advantages over the
      conventional inverse planning schemes: (1) it provides a unified framework for
      inverse planning with beams of arbitrary fluence profiles, including treatment
      with beams of mixed fluence profiles; (2) the use of total-variation constraints
      on NTMs allows us to optimally balance the dose confromality and deliverability
      for a given beam configuration. This project was supported in part by grants from
      the National Science Foundation (0854492), National Cancer Institute (1R01
      CA104205), and Leading Foreign Research Institute Recruitment Program by the
      Korean Ministry of Education, Science and Technology (K20901000001-09E0100
      00110). To the authors' best knowledgement, there is no conflict interest.

PMID- 28518714
TI  - TU-E-BRA-09: Evaluation of a Patient-Specific Respiratory Motion Model in
      Thoracic and Abdominal Phantom and Patient CT Images.
AB  - PURPOSE: We have previously described a model of patient-specific respiratory
      motion to predict organ deformations without assuming repeatable breath cycles.
      The model is derived from deformable image registration (DIR) between respiration
      correlated images (RCCT), followed by a principal component analysis (PCA) which
      relates the first two principal components of 3D deformations to the position and
      direction of motion of the diaphragm or implanted fiducials. This study examines
      model accuracy in phantom and patient images. METHODS: We compare model and DIR
      accuracy using 3 types of image sets, each exhibiting different deformation
      patterns: (1) synthetic images in lung and abdomen from the 4D NURBS-based
      cardiac torso (NCAT) phantom with known deformations; (2) CT scans of physical
      deformable phantom with implanted markers in liver; and (3) liver structures in
      patient RCCT images using rigid registration in a small VOI as approximate ground
      truth. The model is calibrated by applying fast free-form DIR between a reference
      image set at end expiration and each of the other images at different motion
      states, defined by diaphragm or, in some patient cases, implanted fiducials as
      surrogate signals. Following PCA, the first two principal components are selected
      to yield a model-predicted displacement field for the given surrogate signal.
      RESULTS: Discrepancy between model prediction and ground truth (mean +/- stand
      deviation) in 3D displacements is 3.3+/-2.0 mm in lung and 3.7+/-1.9 mm in
      abdomen in NCAT phantom, 3.8+/-2.7 mm in physical deformable phantom and 2.8+/
      2.9 mm in patient data (N=7). Corresponding DIR discrepancies are 3.8+/-2.0 mm
      (NCAT lung), 3.7+/-1.8 mm (NCAT abdomen), 3.6+/-2.8 mm (physical phantom), and
      2.0+/-2.2 mm (patient data). CONCLUSIONS: Motion model accuracy is found to be
      comparable to fast free-form in all three types of images, indicating that the
      assumption of two principal components is sufficient to describe the fast free
      form DIR-derived deformations. NIH/NCI award R01 CA126993.

PMID- 28518732
TI  - Erratum: "Automatic patient alignment system using 3D ultrasound" [Med. Phys.
      40(4), 041714 (7pp.) (2013)].

PMID- 28518891
TI  - SU-E-J-134: Motion Modeling of Non-Small Cell Lung Nodules Based on Respiratory
      Mechanics.
AB  - PURPOSE: To quantify the movements of non-small cell lung nodules using 4D cone
      beam computed tomography (4D-CBCT) that is automatically registered with planning
      CT, and to develop a mathematical model to predict the motion trajectory.
      Modeling the tumor motion may reduce the PTV and ultimately increase the
      therapeutic ratio. METHODS: Absolute coordinates of the lung nodules in 15
      patients were quantified for each phase of 4D-CBCT scans using auto-registration
      methods. Assuming respiration follows an elliptical pattern spatially in the
      lung, these coordinates were fitted to trigonometric functions in each x-y-z
      direction. Adjusting for phase dependence, the motion could be compared
      quantitatively for inter-fractional and intra-patient variations to determine if
      this model is universally applicable and has predictive value. RESULTS:
      Examination of over 36 sets of 4D-CBCT data shows acceptable agreement (< 2mm)
      with the elliptical model for both individual scans and over the course of
      treatment. Some inter-fractional variations in amplitude and cycling periods
      indicate the need to remodel as patients' conditions change. The intra-patient
      variations are significant and strongly dependent on the patient lung volume and
      tumor location, thus individual modeling of tumor motion is expected.
      CONCLUSIONS: The model indicates good agreement and clinical relevance with non
      small cell lung nodule motion, and it appears to be potentially relevant over the
      course of treatment. Most re-acquired 4D-CBCT images inter-fractionally were
      within the baseline spatial resolution of the auto- registration technique.
      However, if remodeling is necessary inter-fractionally, this model still has the
      potential for significant motion margin reduction over the course of treatment.

PMID- 28518892
TI  - SU-E-J-145: Implementing 4D XCAT Phantom for 4D Radiotherapy Research.
AB  - PURPOSE: To characterize and implement the 4D Integrated Extended Cardiac Torso
      (XCAT) digital phantom for 4D radiotherapy (RT) application. METHODS: A computer
      program was developed to facilitate the characterization and implementation of
      the 4D XCAT phantom. The program can (1) generate 4D XCAT images with customized
      parameter files; (2) review 4D XCAT images; (3) generate composite images from 4D
      XCAT images; (4) track motion of selected region-of-interested (ROI); (5) convert
      XCAT raw binary images into DICOM format; (6) analyze clinically acquired 4DCT
      images and Real-time Position Management (RPM) respiratory signal. Validation of
      the motion tracking algorithm was made by comparing to manual method. Major
      characteristics of the 4D XCAT phantom were studied including the dependence of
      lesion motion on its location/size and inputted diaphragm profile. An end-to-end
      test from image generation to treatment planning was also performed. RESULTS: The
      comparison between motion tracking and manual measurements of lesion motion
      trajectory showed a small difference between the two (mean difference in motion
      amplitude: 1.2 mm). The maximum lesion motion decreased nearly linearly (R2=0.97)
      as its distance to the diaphragm (DD) increased. At any given DD, lesion motion
      amplitude increased nearly linearly (R2 range: 0.89 to 0.95) as the inputted
      diaphragm motion increased. For a given diaphragm motion, the lesion motion is
      independent f the lesion size at any given DD. The 4D XCAT phantom can closely
      reproduce irregular breathing profile: the mean difference in motion amplitude
      between the inputted and the measured motion profile was 1.4 mm. The end-to-end
      test showed that clinically comparable treatment plans can be generated
      successfully based on 4D XCAT images. CONCLUSIONS: An integrated computer program
      has been developed to generate, review, analyze, process, and export the 4D XCAT
      images. A robust workflow has been established to implement the 4D XCAT phantom
      for 4D RT application.

PMID- 28518893
TI  - SU-E-J-154: Advantages of Treating Thoracic Cancer Patients in an Upright
      Position.
AB  - PURPOSE: To compare lung volume and respiratory motion in supine and upright
      positions to assess the potential advantages of treating thoracic cancer patients
      in an upright position. METHODS: A multi-position MRI scanner (FONAR, Melville,
      NY) was used to take MRI images of 4 healthy volunteers in both supine and
      upright setup positions (expected total accrual: 15 volunteers). In each case, a
      volumetric scan was acquired during breath-hold at end of normal expiration,
      followed by a series of sagittal cine MR scans taken during normal respiration.
      The exhale volume images were imported into a treatment planning system and lung
      volumes were delineated and compared for different setup positions. The
      trajectory of points inside the lung were tracked in the cine images and analyzed
      using a deformable image registration technique and a principal component
      analysis (PCA) model. RESULTS: The average exhale lung volume was 38% (894cc)
      larger (range: 23%-57%, 570-121 1cc) when volunteers were in the upright position
      compared with the supine position. The amplitude of motion for a set of landmark
      points in the lung volume ranged from <2mm (distant from the diaphragm) to 29 mm
      (close to the diaphragm) in the superior-inferior direction. A linear fit to the
      amplitude of respiratory motion vs. distance from the diaphragm for all 4
      volunteers indicated no difference on averagein the range of motion for the two
      setup positions, but there was variability between individuals. CONCLUSIONS:
      While the magnitude of motion was similar, the absolute lung volumes were much
      larger in the upright position than in the supine position, which suggests that
      treating thoracic patients in the upright position may allow for a reduction in
      the mean lung dose. The study was partially supported by a sponsored research
      grant from Varian Medical Systems.

PMID- 28518894
TI  - SU-E-J-127: An Initial Application of Evaluating Lung Tumor Motion Throughout
      Radiotherapy.
AB  - PURPOSE: We present a novel method for evaluating lung tumor motion incorporating
      planning CT scan, imaging for patient localization, and during treatment
      delivery. METHODS: Tumor motion is evaluated at three stages of the treatment
      process. Following the acquisition of 4D CT scans for treatment planning, tumors
      are contoured at one phase and registered to other phases to obtain tumor motion
      patterns. Tumor motion prior to each treatment is evaluated by identifying tumors
      directly on every raw projection of the daily localization CBCT scans. Finally,
      tumor motion during treatment is evaluated by analyzing MV treatment beam images.
      Every frame of image is evaluated as three components, each with separate DRRs:
      all non-moving structures, the tumor, and other moving structures. The locations
      of three components are determined though a registration process. In order to
      quantify tumor motion, the cumulated probability, the percentage of time when the
      tumor motion is equal to or smaller than a given range, is evaluated at every
      stage. RESULTS: This methodology has been applied to five lung cancer patients
      undergoing radiotherapy. More than 5400 frames from MV treatment beam images and
      24 CBCT scans were acquired from 12 fractions. Both the average tumor position
      and the cumulated probability with the range were evaluated. The tumor motion
      ranges are generally larger than those obtained from 4D CT. Significant variation
      in motion patterns was observed as well. CONCLUSIONS: Information obtained from
      4DCT is insufficient for motion assessment. In contrast, our novel methodology is
      capable of accurately characterizing lung tumor motion on a daily basis, without
      the need for implanted fiducial markers and without additional imaging dose. It
      provides daily verification that the tumor range is within prior estimates and
      covered by the treatment planning volume. This research is supported by CPRIT
      Individual Investigator Award RP110329.

PMID- 28518895
TI  - SU-E-J-138: Fast 2-D Fiducial Marker Detection on Sequential MV Projections in
      Arc Therapy.
AB  - PURPOSE: To automatically detect intrafraction motion during arc radiotherapy for
      prostate cancer patients by tracking fiducial markers in two-dimensional MV
      images acquired using the treatment beam, in order to adjust radiation dose
      accordingly. METHODS: Four fiducial gold markers are implanted in a patient's
      prostate. Patients are irradiated using a Varian Linac 2100 C/D with RapidArc
      upgrade (Varian Medical Systems, Palo Alto, CA). MV images (1024 * 768 pixels,
      0.392 * 0.392 mm2 pixel size) acquired during a 360 degree gantry rotation at a
      one second interval (5 degrees) are preprocessed by subtracting a smoothed
      version of the image to retain only high image frequencies. Edge detection is
      then applied, followed by a one pixel wide dilation and erosion to transform the
      edges into contiguous regions. Next, our method searches the centers of visible
      markers (i.e. not covered by the MLC), constrained by marker estimates from the
      planning CT. This is done by finding all contiguous regions and maximizing a
      marker-region distance criterion for every visible marker. A two-dimensional
      estimate correction over consecutive projections is also implemented to improve
      marker estimates during gantry rotation. RESULTS: We applied our method on four
      treatment fractions of the same patient. As such, a total of 191 projections with
      manually indicated marker ends as ground truth were used as validation. Markers
      were indicated twice on all images, to include observer errors. Results show a
      mean detection error of less than 0.5 mm in the projection image (standard
      deviation 0.6 mm), with an execution time of less than one second per image in
      matlab. Undetected markers and false positives mostly occurred at moving leaf
      boundaries, where marker visibility was determined by the observer. CONCLUSIONS:
      Preliminary findings demonstrate that this method can be used to detect
      intrafraction motion during arc radiotherapy by only using projected MV images.
      Research sponsored by Varian Medical Systems, Palo Alto, CA.

PMID- 28518896
TI  - SU-E-J-148: Fabrication of an Anatomically Realistic Dynamic Respiratory Phantom.
AB  - PURPOSE: The purpose of this project was to design an anatomically correct
      respiratory phantom that allows for accurate dose measurement within thoracic
      structures that move in a realistic fashion allowing for a more accurate
      simulation of in vivo measurements. METHODS: The basis for this phantom is The
      Dynamic Breathing Phantom (TBP), an Alderson Phantom by Radiology Support Devices
      (RSD). The phantom was disassembled, removing the proprietary pneumatic lung
      apparatus as well as the motor driven tumor mount. A CT of the phantom at rest in
      the exhale position was acquired with 0.25 cm slice thickness. Every sixteenth
      slice was printed out to scale. The lung cavity was segmented on the images.
      These were used to cut out 4.0 cm thick slabs of foam rubber matching the contour
      of the lung. These were assembled along with other thoracic structures manually
      imbedded in the foam rubber. The organs were then placed within the chest cavity
      of the phantom. A purpose-built diaphragm chamber made of a rubber bladder was
      inserted under the lung material. The manufacturer-provided air compressor system
      was re-tasked to drive the diaphragm chamber. RESULTS: The foam rubber used as
      lung material has comparable density to human lung (-800 HU). The phantom is
      capable of producing realistic respiratory motion. This phantom will easily
      accommodate a variety of dosimeters and can be adapted for a variety of
      tumor/critical structure shapes, sizes and locations. CONCLUSIONS: The creation
      of this versatile humanoid phantom opens the door for a multitude of experiments
      to investigate dose to organs within the chest cavity for different planning
      techniques, under different respiratory condition, while using a more
      anatomically correct experimental setup.

PMID- 28518898
TI  - SU-E-J-158: A Prototype of a Real-Time Respiratory Motion Monitoring System Using
      Microsoft Kinect Sensor.
AB  - PURPOSE: To investigate the feasibility of a low-cost respiratory motion
      monitoring system based on the Microsoft Xbox Kinect sensor. METHODS: We improved
      Kinect's inherent depth resolution from 1 cm to 1 mm via a motion magnification
      system. Using the Kinect software development kit, we programmed the Kinect to
      capture depth images and determine the average depth over a thoracic region of
      interest, viewed almost parallel to the subject's surface. Kinect respiratory
      traces (average depth vs time at a rate of 30 Hz) were acquired from four
      volunteers and compared with those simultaneously acquired using a commercially
      available strain gauge respiratory gating system. RESULTS: The correlation
      coefficient (CC) between Kinect and strain gauge traces varied from 0.958 to
      0.978, with a mean CC of 0.969. This strong correlation was also demonstrated by
      the joint probability distribution and visual inspection. CONCLUSIONS: This work
      demonstrates the feasibility of using the Kinect for respiratory motion tracking.
      Traces are similar to those of a clinically used strain gauge system. The Kinect
      based system provides a new and economical way to monitor respiratory motion.

PMID- 28518899
TI  - SU-E-J-131: Implement a Passive Breath Gating Equipment for Gated CBCT Imaging: A
      Feasibility Study.
AB  - PURPOSE: To investigate the feasibility of using a patient passive breath gating
      (PBG) equipment in kilo-voltage cone-beam CT (kVCBCT) image acquisition to reduce
      the respiratory induced motion artifacts for image-guided radiotherapy. METHODS:
      A PBG equipment developed in our department was used to passively block patient's
      breathing. Assisted by this device, patients were able to hold their breaths for
      15-25 seconds. An infrared block was placed on the patient's body and the breath
      hold was triggered by the signal from the Varian RPM system. Three sets of kVCBCT
      images were acquired using the same imaging parameters with the OBI system on
      Varian Trilogy for a gastric cancer patient: free breathing (FB), with two-breath
      hold (BH1) and three-breath-hold (BH2). Patient was allowed to breathe normally
      for 5-10s between breath-hold. A planning CT was obtained with one breath-hold on
      a conventional 4D CT scanner. The diaphragm position on FB, BH1 and BH2 CBCT
      images was compared with its position on the planning CT to assess the motion
      artifacts. RESULTS: The acquisition time for each of the three kVCBCTs was 60
      seconds. The patient tolerated the breath-hold CBCT scanning well. Severe image
      blurriness and streak artifacts caused by respiratory motion were observed near
      the diaphragm on FB CBCT. However, for the breath-hold CBCT images, the motion
      artifacts were reduced and the diaphragm edge was restored. Two-breath-hold scan
      (BH1) produced better image quality than three-breath-hold (BH2). The details of
      the diaphragm edge on BH1 images were comparable to the planning CT. CONCLUSIONS:
      Diaphragm motion causes image distortion in FB CBCT. The PBG can be used in
      kVCBCT acquisition to reduce motion artifacts. The breath-hold kVCBCT can produce
      higher image quality for image-guided radiotherapy and adaptive radiotherapy in
      the thorax and abdominal regions. Conflict of Interest (only if applicable):
      Research supported by Varian Medical System. This work is partly supported by
      Varian Medical System.

PMID- 28518897
TI  - SU-E-J-179: Requirements for the Accuracy of Electron Density Data Planning for
      MRI Based Cervix Cancer Treatment Planning.
AB  - PURPOSE: A sensitivity analysis of the effect of variations in electron density
      data (ED) on dose calculation accuracy for MRI based cervical cancer treatment
      planning. METHODS: Five cervical cancer patients were analysed in this work.
      Planning CT scans represented gold standard ED data. Standard four field 3DCRT
      plans (prescription 45Gy) were designed on these CT scans. The CT data was then
      manipulated to simulate the following methods of assigning ED to MRI; (1)
      homogenous bulk density corrections, (2) Bulk density correction to bones, (3)
      rigid image registration of CT to MR, and (4) regression analysis based pseudo
      CT. Plans were then generated on the manipulated data sets, and compared to the
      plans generated on the original. Dose was analysed using Chi analysis and
      equivalent uniform dose (EUD). Data was analysed to quantify (A) the effect on
      plan design (called optimisation error), and (B) the effect on dose calculation
      accuracy (systematic error). RESULTS: Analysis of the averaged patient results
      showed that for 3DCRT, the use of imperfect electron density data had minimal
      impact on plan design for all tested data sets. Analysis of systematic error
      showed minimal errors for cases (1), (2) and (3), where average errors of less
      than 0.3 Gy in EUD were recorded and Chi analysis showed that over 95% of points
      within the high dose region (D>36Gy) were within 2% or 2mm of the original dose.
      For case (4), errors greater than .5 Gy in EUD were recorded; these were not
      considered acceptable errors. CONCLUSIONS: Using imperfect electron density data
      for 3DCRT treatment planning for cervical cancer patients is feasible for
      appropriately considered choices of electron density assignment. Further analysis
      is needed to test this result for IMRT, and is ongoing.

PMID- 28518901
TI  - SU-E-J-174: ITV Variations as a Function of CT Geometry and Scan Time : A
      Simulation Study Using Patient Data.
AB  - PURPOSE: The internal target volume (ITV) accounts for uncertainties in tumor
      position and shape and is defined from images acquired with 4DCT. In this work,
      the locations of gold fiducial markers implanted in lung tumors of seven patients
      are used to represent tumor motion and investigate the role of the CT scanner
      geometry and scan duration on ITV definition. METHODS: All of the simulations are
      geometric simulations performed in MATLAB (The Mathworks, Nattick,MA) and
      variations in image reconstruction are not considered. The CT scanner geometries
      simulated include a 4-slice CT scanner (with an axial field of view of 10 mm) and
      an 'ideal' CT scanner geometry that covers all potential tumor positions in the
      same bed position (axial field of view of 100 mm). The scan durations were varied
      from 6 seconds per bed position to 30 seconds per bed position. For all of the
      simulations, the tumor was modeled as a sphere of diameter 25 mm. The ITVs were
      compared by calculating the mean ITV for each patient and scan parameters.
      RESULTS: For all of the patients, the mean ITV increased as the scan duration
      increased. The maximum increase in mean ITV was 25%. CONCLUSIONS: This work
      highlights the potential benefit of modified CT protocols to determine the ITV.
      One example of a modified protocol would be to increase the scan duration (to
      decrease ITV uncertainties) while decreasing the mA of the scanner (to avoid
      giving extra radiation dose). The largest factor influencing the ITV is the scan
      duration (and not the scanner geometry).

PMID- 28518900
TI  - SU-E-J-142: Gafchromic Film Dosimetry in Fluoroscopy for Dynamic Tumor Tracking
      Irradiation of the Lung Using XR-SP2 Model - A Phantom Study.
AB  - PURPOSE: We have recently developed a dynamic tumor tracking irradiation system
      using Vero4DRT (MHI-Tm2 000). It is needed to create a 4D correlation model
      between a fiducial marker implanted near a tumor and an external surrogate as a
      function of time by continuously acquiring both fluoroscopy images and external
      surrogate signals. The purpose of this study was to propose a new dosimetry
      method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy
      imaging. METHODS: First, half-value layers (HVLs) were measured using aluminum
      (Al) thicknesses (15 mm) at 40125 kVp. Subsequently, several films were
      irradiated using various milliampere second values on a solid water phantom. The
      surface air kerma were also measured using the chamber to calculate the surface
      doses under the same condition. Then, the calibration curve of dose vs. pixel
      values was calculated. Finally, surface dose by fluoroscopy imaging was measured
      using several pieces of film taped on the chest phantom. Orthogonal X-ray
      fluoroscopy imaging was simultaneously performed until completion of data
      acquisition for creating a 4D correlation model. Those films were scanned after
      irradiation using a flat-bed scanner and converted to dose by calibration curve.
      RESULTS: The HVLs for tube voltage within 40125 kVp ranged from 2.35 to 5.98 mm
      Al. The calibration curve between surface dose and pixel values was reasonably
      smooth. The differences between the measured and the calibrated doses were less
      than 3%. The hot spots with the maximum dose of 37.12 mGy were observed around
      the area overlapped by both fluoroscopic fields. CONCLUSIONS: We have proposed a
      new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by
      fluoroscopy imaging. This phantom study has demonstrated that it may be feasible
      to assess surface dose to patients during dynamic tumor tracking irradiation in
      clinic with ease after further investigation. This research was supported by the
      Japan Society for the Promotion of Science (JSPS) through its Funding Program for
      World-Leading Innovation R&D on Science and Technology (FIRST Program). Research
      sponsored in part by Mitsubishi Heavy Industries, Ltd.

PMID- 28518903
TI  - SU-E-J-167: Optimal Number of Respiratory Phases in 4D PET for Radiotherapy
      Planning: Motion-Simulated Phantom Study.
AB  - PURPOSE: Four-dimensional PET/CT is increasingly used in radiotherapy treatment
      planning. One issue that is still under investigation is the optimal number of
      bins or phases into which the respiratory cycle needs to be divided. We performed
      4D PET moving phantom study and compared results between 6 and 10 bins. METHODS:
      A Jaszczak PhantomTM containing six hollow spheres (0.95 - 3.18 cm inner
      diameters) was used. Three sinusoidal motion patterns were accomplished with peak
      to-peak amplitudes of 1, 1.5 and 2.0 cm with a respiratory period of 5 s. The
      background and the six spheres were filled with 18F-FDG solution to achieve three
      SBR: 1:3.65, 1:7.95, and 1:10.22. Data were collected in 3-D mode for 10 min.
      Images were reconstructed using OSEM reconstruction: 32 subsets with 2
      iterations, variable FWHM Gaussian post-filter 5-8 mm, and using image matrix
      sizes of 128*128, 192*192 and 256*256. The spheres were auto-segmented using pre
      calculated optimal thresholds for a 1:1 volumetric correlation between actual-
      and PET-delineated spheres from static phantom studies. RESULTS: According to the
      static data the following set of parameters are optimal for static PET target
      (sphere) delineation: OSEM reconstruction with 32 subsets and 2 iterations, FWHM
      of 5 mm, and image size 256*256. The 4D data studies (with pre-calculated optimal
      thresholds) have shown that a 6-bin set shows less volume distortions then the 10
      bin set. CONCLUSIONS: The authors found that 6-bin reconstruction is more
      reliable for delineation of a target in motion than 10-bin reconstruction.
      Further investigation with optimal thresholds obtained from 4D data, not static,
      is required no conflict of interest for all authors.

PMID- 28518902
TI  - SU-E-J-152: Prostate IGRT: CT-MRI Fusion and Target Delineation Accuracy.
AB  - PURPOSE: The accuracy of CT-MR imaging fusion plays an important role in both
      accurate delineation (using MR data) and dose calculation (using CT data) for
      image-guided radiotherapy (IGRT) of prostate cancer. The purpose of this study
      was to investigate the accuracy of CT-MRI fusion in target
      delineation/localization for prostate IGRT. METHODS: Sixty-nine prostate patients
      were included in this study. Each patient underwent CT/MR simulation prior to the
      IMRT or RapidArc treatment. Paired CT-MR images were obtained using a GE 4D-CT
      scanner and a GE 1.5T MR scanner. MR and CT scans were performed within 30min to
      minimize organ or structure changes except for Calypso patients who received MR
      scans prior to the Beacon implantation. Prostate, rectum and bladder were
      delineated on CT and MRI, respectively. The difference of prostate centers and
      the volume variation between CT and MRI were calculated and used as the index for
      image fusion accuracy. RESULTS: With bony structure matching, all bony structures
      were fused well between CT and MRI. However, the changes in bladder and rectum
      fillings between CT and MRI dislocate the prostate and the surrounding
      structures. The maximal shift of the prostate in the AP direction was up to 8mm
      and about 15.9% of the patients showed a shift >3mm, which was proportional to
      the difference of the rectum volume. The shift in the SI direction was 0.5-5mm.
      Of the 11 patients who had >3mm shifts, 6 patients (54.5%) were Calypso patients.
      CONCLUSIONS: Significant geometrical shifts of the prostate target were observed
      correlated with large differences in the bladder/rectal volume between CT and MR
      images especially for large CT-MRI intervals. Attention must be paid to the
      residual fusion error for the soft tissue target and corrections should be made
      to ensure target delineation accuracy if necessary.

PMID- 28518904
TI  - SU-E-J-178: Development of Image Planning System for Radiation Therapy.
AB  - PURPOSE: The constraints required for patient imaging dose received during image
      guided radiotherapy differ from those applied in the diagnostic realm. Wide
      latitude in applied dose can be justified if it results in useful improvement in
      image quality. Currently, image acquisition parameters are chosen via broad
      categorizations in patient anatomy and imaging goal. Herein, we describe the
      development and early benchmarking of a patient-specific image planning system
      that is capable of predetermining the optimal acquisition parameters for a given
      level of patient dose and imaging goal. METHODS: An algorithm was written in
      Matlab that performed a divergent ray-trace through a 3D CT data set and impinges
      on a flat imaging receptor. Energy-specific attenuation through each voxel of the
      CT data set is calculated to derive a net transmitted intensity. The detector
      response as a function of beam quality and exposure was measured and integrated
      into the algorithm. It is primarily this feature that distinguishes this from a
      traditional digitally reconstructed radiograph. Verification data was collected
      using a flat panel imager mounted onto a linear accelerator gantry and a lung
      phantom with an embedded nodule. Loss of object detectability was evaluated by
      measuring the visible diameter of the phantom nodule. RESULTS: There is
      qualitative agreement between simulated and measured images in terms of contrast
      and object detectability. The simulation algorithm predicts both under-exposure
      and saturation of the detector over a range of beam qualities (80 keV to 120keV)
      and exposure levels. Object detectability erodes predictably above 60 mAs for at
      80keV and above 15mAs for 120 keV for both simulated and measured images.
      Quantitative accuracy is currently limited by lack of beam heterogeneity, which
      will be added in further work. CONCLUSIONS: The feasibility and qualitative
      accuracy of an image planning system has been established.

PMID- 28518905
TI  - SU-E-J-144: Recurrence Quantification Analysis of Lung Cancer Patients' Breathing
      Pattern.
AB  - PURPOSE: To demonstrate that Recurrence quantification analysis (RQA) can be used
      as a quantitative decision making tool to classify patients breathing pattern and
      select treatment strategy for maneuvering the tumor motion : (a) MIP based
      treatment (b) 4D treatment using non-linear prediction only (c) 4D treatment non
      linear control prediction and breathing control. METHOD AND MATERIALS: In our
      previous work we established that breathing patterns can be described as a 5-6
      dimensional nonlinear, stationary and deterministic system that exhibits
      sensitive dependence on initial conditions. Recurrence plots enable one to
      investigate an m-dimensional state space trajectory through a two-dimensional
      representation of its recurrences where the value of a specific pixel is 1 if the
      distance between the two corresponding trajectory points is less than a threshold
      value epsilon. Important measures calculated are: Recurrence Rate (RR),
      %Determinism, Divergence, Shannon Entropy, LMean, and Renyi entropy (K2). Time
      Resolved RQA: By implementing a sliding window design, each of the above
      calculated parameters is computed multiple times. Alignment of those parameters
      with the time series reveals details not obvious in the 1 -dimensional time
      series data. The breathing pattern for seven randomly chosen volunteers were
      recorded using the RPM system for 15 minutes. Non-linear prediction was performed
      and the normalized root mean square error (NRMSE) was calculated for each of the
      volunteer data. RESULTS: The threshold value epsilon was chosen such that the
      Recurrence Rate was equal to 1%. There is a strong correlation of NRMSE with
      Entropy, Determinism and LMean. Time resolved RR locates strong Unstable Periodic
      Orbits(UPOs), i.e. patterns of uninterrupted equally spaced diagonal lines.
      CONCLUSIONS: RQAs could prove to be a very powerful tool for design of
      personalized treatment regimen. Entropy, Determinism in conjunction with strong
      UPOs can be used to determine if patients are suitable candidates for prediction
      and chaos control.

PMID- 28518906
TI  - SU-E-J-153: Volumetric and Dosimetric Variations of Post-Prostatectomy Patients
      Treated with Radiation Therapy and Endorectal Ballon.
AB  - PURPOSE: Post-prostatectomy patients may be treated with endorectal balloon (ERB)
      placed during the radiation therapy. The objectives of this tudy are to
      investigate geometrical variation of organs at risk (OAR) and CTVs (based on RTOG
      and EORTC guidelines) throughout the course of radiation therapy and their
      dosimetric impact. METHODS: Six consecutive post-prostatectomy patients enrolled
      on a prospective IRB approved institutional study were analyzed. Patients
      underwent CT/MRI simulation and treatment with daily endorectal balloon (ERB).
      Six T2-MRI scans were performed during the treatment course. Bladder, rectum and
      two sets of CTVs according to the RTOG and EORTC guidelines were contoured by
      physician on each of the weekly MRI scans. The MRI scans were subsequently
      rigidly fused to the CT simulation images to simulate daily kV-kV patient
      alignment. RESULTS: 1. A consistent trend of decreasing bladder volume was found
      after the first week of treatment and therefore the V65Gy was found to increase
      after the second week of the treatment.2. The rectal volume with ERB was found to
      be relatively consistent during the treatment course. Displacements of rectal
      contours were within 2mm in all directions. The V60Gy<20% (our institutional
      rectal constraint) varied on average less than 2%.3. We found that the CTV
      volumes contoured per EORTC guideline exhibits a larger variation than those
      drawn according to the RTOG guidelines most likely due to the bladder exclusion
      imposed by it. While the average variation of RTOG based CTV volume was found
      within 5%, the variation of CTV-EROTC volumes was more then 10%) (p = 0.06).
      CONCLUSIONS: In post-prostatectomy patients undergoing radiotherapy with daily
      ERB had a consistent decrease in the bladder volume during the treatment leading
      to increased bladder irradiation and changes in the CTV volumes predominantly
      when EORTC guideline were followed.

PMID- 28518907
TI  - SU-E-J-126: Generation of Fluoroscopic 3D Images Using Single X-Ray Projections
      on Realistic Modified XCAT Phantom Data.
AB  - PURPOSE: To simulate the process of generating fluoroscopic 3D treatment images
      from 4DCT and measured 2D x-ray projections using a realistic modified XCAT
      phantom based on measured patient 3D tumor trajectories. METHODS: First, the
      existing XCAT phantom is adapted to incorporate measured patient lung tumor
      trajectories. Realistic diaphragm and chest wall motion are automatically
      generated based on input tumor motion and position, producing synchronized,
      realistic motion in the phantom. Based on 4DCT generated with the XCAT phantom,
      we derive patient-specific motion models that are used to generate 3D
      fluoroscopic images. Patient-specific models are created in two steps: first, the
      displacement vector fields (DVFs) are obtained through deformable image
      registration of each phase of 4DCT with respect to a reference image (typically
      peak-exhale). Each phase is registered to the reference image to obtain (n-1)
      DVFs. Second, the most salient characteristics in the DVFs are captured in a
      compact representation through principal component analysis (PCA). Since PCA is a
      linear decomposition method, all the DVFs can be represented as linear
      combinations of eigenvectors. Fluoroscopic 3D images are obtained using the
      projection image to determine optimal weights for the eigenvectors. These weights
      are determined through iterative optimization of a cost function relating the
      projection image to the 3D image via the PCA lung motion model and a projection
      operator. Constructing fluoroscopic 3D images is thus reduced to finding optimal
      weights for the eigenvectors. RESULTS: Fluoroscopic 3D treatment images were
      generated using the modified XCAT phantom. The average relative error of the
      reconstructed image over 30 sec is 0.0457 HU and the standard deviation is
      0.0063. CONCLUSIONS: The XCAT phantom was modified to produce realistic images by
      incorporating patient tumor trajectories. The modified XCAT phantom can be used
      to simulate the process of generating fluoroscopic 3D treatment images from 4DCT
      and 2D x-ray projections.

PMID- 28518908
TI  - SU-E-J-137: A Theoretical Model for the Analysis of Residual Motion Artifacts in
      4D CT Scans.
AB  - PURPOSE: The purpose of this study was to analysis the residual motion artifact
      in 4D-CT scan using a simple one-dimension theoretical model. METHODS: In order
      to evaluate the target displacement at each phase image, We used phantom (Dynamic
      Thorax Phantom, CIRS, Norfolk, VA) which could control programmable regular 1D
      sine motion and belt type respiratory monitoring system. 2cm diameter spherical
      target was inserted in the phantom and then we set-up regular 1D sine motion and
      adjusted three level of amplitude (10, 20, 30 mm) with fixed period (4s). Four
      dimensional (4D) CT images were acquired by CT scanner (Sensation Open, Siemens
      Medical Systems, Forchheim, Germany) with a slice thickness of 1.5 mm and 0.1
      pitch in helical mode. Respiratory monitoring system (AZ-733V, Anzai MEDICAL) was
      placed on the abdominal surface of phantom, and the respiratory signal was
      acquired. CorePLAN (RTP, SC&J) software was used to acquire static target
      diameter and each ten phase diameters. RESULTS: The displacements (?S) peak at
      the 20~30% or 70~80% phases, and are minimized at the 50% phase. This is because
      the target velocity is minimum at 50% phase and maximum at 30 and 70% phases;
      hence, the large image blur. The measured diameters of target are compared to the
      simulation results and we observed similar trends of target diameter change.
      CONCLUSIONS: In this study, we presented simple one-dimensional model to analyze
      the residual motion artifact in 4D-CT scan. The model was used to explain the
      effect of residual motion on each phase target displacement and also shown that
      residual motion artifact was affected that the target velocity at each phase.
      Lastly based on this model, we developed simulation program and acquired similar
      results of target displacement compared with measured data. This research was
      supported by Leading Foreign Re-search Institute Recruitment Program through the
      National Research Foundation of Korea (NFR) (Grant No. K20901000001-09E0100
      00110,) and the program of Basic Atomic Energy Research Institute (BAERI) which
      is a part of the Nuclear R and D Programs (No.20110006324) funded by the Ministry
      of Education, Science and Technol-ogy(MEST).

PMID- 28518909
TI  - SU-E-J-147: Dosimetric Consequences of Intrafraction Prostate Motion: Comparison
      Between Phantom Measurements and Three Different Calculation Methods.
AB  - PURPOSE: Evaluation of different calculation methods for dose modification due to
      intrafraction prostate motion using film measurements as ground truth. METHODS:
      We acquired intrafraction motion data with the Calypso tumor tracking system by
      Varian Medical Systems Inc for 4 prostate IMRT patients treated with 35 fractions
      each. These motion data were transferred to a phantom platform which reproduces
      the observed motion and has a 20 cm diameter cylindrical solid water phantom
      mounted. For each patient all fractions were irradiated on one radiochromic MD-V2
      55 film placed in the isocentric transversal slice of this phantom. These films
      serve as ground truth for three calculation Methods: 1) Recalculation of the plan
      with shifted target point for every segment with the segment's mean Calypso
      position. 2)+3) Convolution of the static dose distribution with a probability
      density function of the observed positions. For 2) only Calypso positions with
      activated beam on signal were used whereas for 3) all Calypso positions between
      the first and the last beam on signal for all fractions were employed. The
      comparisons between films and calculated dose distributions were made with the
      verification software VeriSoft 3.2 (PTW, Freiburg, Germany) where an 8*8 cm2 ROI
      around the isocenter was selected for gamma evaluation. RESULTS: The segment
      shifted plans reach 3%/3mm gamma values above 90% against the films for all four
      patients. For both convolution methods three values are above 90%, only for the
      patient with the largest intrafraction motion they decrease to 89%. CONCLUSIONS:
      Shifting of the target point for every segment is well suited to estimate the
      dosimetric consequences of intrafraction prostate motion. This may facilitate the
      evaluation of different margin sizes or dose prescribing recipes under different
      motion conditions. If such a lengthy calculation is not possible, a convolution
      with motion data can be used for acceptable results, too. Our work was partially
      supported by Siemens Healthcare and Varian Medical Systems Inc.

PMID- 28518910
TI  - SU-E-J-157: Simulation and Design of a Real-Time 6D Head Motion Compensation
      Platform Based on a Stewart Platform Approach.
AB  - PURPOSE: Real-time sub-millimeter head motion compensation during frameless SRS
      delivery has the potential to achieve the accuracy of frame-based SRS while being
      significantly less invasive. Previously, we demonstrated real-time 6D head motion
      monitoring using an optical camera, however, at the time we were limited to only
      3D (x-y-z) of head motion correction due to mechanical restrictions of the head
      platform. In this work we investigate the feasibility of using a compact 6D
      robotic Stewart platform (hexapod) placed under the patient's head to perform
      both translational and rotational motion compensation in real-time. Benefits of a
      hexapod approach over a conventional serial kinematics stage include less flex,
      compactness, high force to weight ratio, and fast response times. METHODS: A
      hexapod is a parallel robotics device consisting of two platforms connected by
      six linear actuators oriented at particular angles. To provide accurate motion in
      6D, the desired position of the top platform (head) was ascertained using inverse
      kinematics. MATLAB was used to simulate the six actuator positions for performing
      motion along x-y-z-phi -theta-psi. Prior recorded 6D human volunteer head motion
      data was used as an input for simulation of motion compensation. Six Firgelli L12
      P linearservo actuators, together with a PCI-7344 motion controller and Labview
      software, were used for initial construction of a hexapod prototype. RESULTS: The
      necessary actuator lengths over time were computed for this data, simulating the
      required 6D movement of the hexapod for motion correction. Simulations on
      previously collected volunteer data indicate a hexapod system is capable of
      responding to subject head motion with corrections of precise movements, and
      solutions to the linear system can be computed at near real-time speeds.
      CONCLUSIONS: Based on simulated results, it was successfully demonstrated that a
      hexapod device can compensate for small patient head motions along all six
      degrees of freedom.

PMID- 28518911
TI  - SU-E-J-130: Study of the Image Quality Degradation in Phase-Based 4DCT Imaging
      for Radiation Oncology.
AB  - PURPOSE: Four-dimensional computed tomography (4DCT) integrated into radiation
      imaging system is a useful tool for accurate targeting. 4DCT has the ability to
      minimize breathing related artefacts compared to conventional CT but irregular
      breathing and large tumour motion may cause inappropriate reconstruction. Our aim
      is to estimate the image quality degradation of 4DCT and to assess the clinical
      consequences. METHODS: The performance of the respiratory gating system of the
      multi-slice CT-simulator Brilliance Big Bore was evaluated employing one
      dimensional moving phantom. The binning algorithm was phased-based. 4DCT scans of
      the test-phantom were acquired applying periodic motion patterns characterized by
      amplitude and frequency spanning a clinically range and also irregular waveforms
      simulating realistic breathing cycles. The internal spherical objects of the
      moving phantom were contoured using semiautomatic segmentation for evaluating
      uncertainties in volume delineation and motion amplitude calculation. Motion
      amplitude was determined by a specially written MATLAB program. Afterwards we
      investigated the influence of the image distortions on the targeting and the
      consequences of the related uncertainties on the calculated dose distribution of
      the tumour and the lungs in a group of five lung-cancer patients. RESULTS: The
      results obtained with the phantom show that 4DCT imaging is still affected by
      distortions due to residual motion. The inaccuracies are mainly related to the
      amplitude (R2=0.99, R2=0.97 for 20 mm-dia sphere and 10 mm-dia sphere,
      respectively) and to the oscillation frequency (R2=0.87 for 20 mm-dia sphere,
      R2=0.96 for 10 mm-dia sphere) of simulated respiratory cycle and can cause both
      underestimation and overestimation of the real tumour motion amplitude with an
      average difference between real and calculated amplitude of about 10%.
      CONCLUSIONS: The resulting inaccuracies on the internal tumour volume delineated
      do not have significant clinical consequences on lung doses but they could be
      important on tumour dose distribution if they imply underestimation of the real
      tumour motion.

PMID- 28518912
TI  - SU-E-J-163: Video-Based Patient Motion Detection during the Treatment Delivery.
AB  - PURPOSE: During the treatment, a patient is continuously monitored by video
      cameras. The therapists are supposedly to watch the monitors and interrupt the
      treatment if any significant patient motion is spotted. Unfortunately, patient
      motion can easily be overlooked with this manual approach, especially when there
      are many other monitors in the control console area. Motion detection algorithms
      can help to prevent this situation by alerting therapists if a significant motion
      is detected. METHODS: We propose a method based on matrix decomposition into low
      rank and sparse matrices to separate background and moving objects from a video
      camera. The matrix is formed with image frames of the video and after
      decomposition, the low rank component represents the background and the sparse
      component is used to identify moving subjects in the video. The matrix
      decomposition is performed by solving a convex optimization problem via an
      efficient alternating direction method. Combining prior knowledge about the
      motion of treatment machines, our method can reliably extract the actual patient
      motion from the machine motion and background changes. RESULTS: We tested the
      algorithm using videos obtained from a volunteer lying on the treatment couch
      under the linac. We managed to isolate the patient and treatment machine motions
      from the background. CONCLUSION: Our algorithm can separate the patient motion
      from the background and therefore makes it possible to efficiently detect when
      this motion is above a certain threshold. This method requires that a large
      number of frames are acquired, but the concept can be extended to real time by
      adaptively update the low rank component.

PMID- 28518914
TI  - SU-E-J-173: Can a Metal Artifact Reduction Algorithm Affect Accuracy of Dose
      Calculation?
AB  - PURPOSE: In external beam radiotherapy, the presence of metal implants such as
      hip prostheses causes significant streak artifacts in planning images, thus
      affecting the accuracy of target and critical organ delineation. The purpose of
      this study is to evaluate the improvement of image quality and impact on accuracy
      of dose calculation by using a commercially available metal artifact reduction
      (MAR) algorithm. METHODS: Nine patients were selected for this study, including 5
      patients with unilateral hip prostheses for orthopedic irradiation, and 4
      patients with unilateral or bilateral hip prostheses for prostate cancer
      treatment. For each patient, simulation CT image was reconstructed with and
      without MAR correction. Contours of the prostate, bladder and rectum were
      delineated on both images by an experienced physician for the prostate patients.
      The difference of contours between MAR corrected and un-corrected images was
      quantified by an overlap index, and dose calculation accuracy was evaluated for
      both target and critical organs. RESULTS: For orthopedic patients, dose
      difference between MAR corrected and un-corrected images was negligible: 0.1+/
      0.1% for maximum dose and 0.8+/-1.8% for dose at isocenter. For prostate
      patients, no significant dosimetric difference was observed between MAR corrected
      and un-corrected images if same contours were used in the treatment planning. For
      the PTV, the average dose variation in D99 was 0.9+/-0.6%. The dose differences
      in D50 of the bladder and rectum were 1.0+/-0.8% and 0.4+/-0.3%, respectively.
      The average overlap index of prostate between the two images was 0.86+/-0.12 for
      patients with bilateral hip replacements. Substantial changes in the dose-volume
      histograms were observed if different contours were used in the treatment
      planning. CONCLUSIONS: The commercial MAR algorithm can improve the image quality
      dramatically and the MAR corrected images do not affect dose calculation
      accuracy. The improvement of accuracy in organ delineation provides significant
      dosimetric advantage. Philips Healthcare.

PMID- 28518913
TI  - SU-E-J-141: Assessment of the Magnitude and Impact of Trigger Delay in
      Respiratory Triggered Real-Time Imaging during Radiotherapy.
AB  - PURPOSE: To assess the trigger delay in respiratory triggered real-time imaging
      and its impact on image guided radiotherapy (IGRT) with Varian TrueBeam System.
      METHODS: A sinusoidal motion phantom with 2cm motion amplitude was used. The
      trigger delay was determined directly with video image, and indirectly by the
      distance between expected and actual triggering phantom positions. For the direct
      method, a fluorescent screen was placed on the phantom to visualize the x-ray.
      The motion of the screen was recorded at 60 frames/second. The number of frames
      between the time when the phantom reached expected triggering position and the
      time when the screen was illuminated by the x-ray was used to determine the
      trigger delay. In the indirect method, triggered kV x-ray images were acquired in
      real-time during 'treatment' with triggers set at 25% and 75% respiratory phases
      where the phantom moved at the maximum speed. 39-40 triggered images were
      acquired continuously in each series. The distance between the expected and
      actual triggering points, d, was measured on the images to determine the delay
      time t by d=Asin(wt), where w=2pi/T, T=period and A=amplitude. Motion periods of
      2s and 4s were used in the measurement. RESULTS: The trigger delay time
      determined with direct video imaging was 125ms (7.5 video frames). The average
      distance between the expected and actual triggering positions determined by the
      indirect method was 3.93+/-0.74mm for T=4s and 7.02+/-1.25mm for T=2s, yielding
      mean trigger delay times of 126+/-24ms and 120+/-22ms, respectively. Although the
      mean over-travel distance is significant at 25% and 75% phases, clinically, the
      target over-travel resulted from the trigger delay at the end of expiration (50%
      phase) is negligibly small(< 0.5mm). CONCLUSIONS: The trigger delay in
      respiration-triggered imaging is in the range of 120-126ms. This delay has
      negligible clinical effect on gated IGRT.

PMID- 28518915
TI  - SU-E-J-151: Evaluation of a Real Time Tumour Autocontouring Algorithm Using In
      Vivo Lung MR Images with Various Contrast to Noise Ratios.
AB  - PURPOSE: To quantitatively evaluate a lung tumour autocontouring algorithm using
      in-vivo lung cancer patient MR images with varying contrast to noise ratios (CNR)
      simulating images acquired at various MR field strengths. METHODS: A non small
      cell lung cancer patient with posterior lung tumour is imaged (sagittal plane) in
      a 3T MRI using a dynamic bSSFP sequence (FOV: 40*40cm2 , voxel size:
      3.1*3.1*20mm3 , TE = 1.1ms. TR = 2.2ms, 275ms per image) under free breathing for
      approximately 3 minutes (650 images). Gaussian random noise is added to the 3T
      images to approximately simulate the equivalent CNR in images acquired at 1.5T,
      1.0T, 0.5T, 0.3T and 0.2T. The moving tumour in all 3T images is contoured by a
      physician for reference. The first 20 of these manual contours are used for the
      parameters optimization of auto-contouring algorithm. The automatic contours from
      the remaining images are quantitatively compared with the physician's contours
      using the centroid's displacement and the Dice's coefficient (DC). RESULTS: The
      oncologist's contours of the 3T images show a maximum S-I motion of 26mm.
      Compared to the oncologist's contours, automatic contours have an average
      centroid displacement of 1.37mm, and an average DC of 0.881. The autocontouring
      algorithm's performance with images in the range of 1.5T to 0.5T equivalent CNRs
      is similar to that of the 3T data. However, for the lowest CNR datasets (0.2,
      0.3T) an increase in centroid displacement and decrease in DC is observed, with
      mean displacements of 1.56mm, 1.71mm and DCs of 0.870, 0.836 for the 0.3T and
      0.2T dataset, respectivelyConclusions: With in-vivo MR images, the autocontouring
      algorithm generated lung tumour contours similar to ones drawn by a physician (DC
      > 0.83). In this patient, additional CNR from >0.5T MRIs does not provide
      statistically significant improvement in the accuracy of our autocontouring
      software. E.Yip is supported by the Canadian Institutes of Health Research as
      well as Alberta Innovates - Health Solutions.

PMID- 28518916
TI  - SU-E-J-123: Blinded Clinician Evaluation of Amplitude versus Phase Binned 4DCT
      Patient Data.
AB  - PURPOSE: The purpose of this study is to evaluate the clinician's perspective of
      amplitude versus phase-based binning of four-dimensional computed tomography
      (4DCT). METHODS: Ten random lung cancer patients were selected with 10-phase
      binned 4DCT's acquired on a Philips BigBore (Philips Healthcare, Andover, MA).
      The data was re-binned using the amplitude of the respiratory signal and a new 10
      phase 4DCT dataset was generated. These two datasets were coregistered and shown
      together for each patient in cine mode in MIMVista (MIM Software, Cleveland, OH).
      Nine clinicians were shown the images and asked to determine if one dataset was
      more clinically beneficial or if there was no difference. The clinicians were
      blinded to the nature of each dataset and to each other's' responses. The data
      were tabulated using a point system where each patient was given +1 point if the
      amplitude binned image was selected, -1 point if the phase binned image was
      selected, and 0 points if they looked the same. RESULTS: The results showed large
      variations from patient to patient. Scores ranged from -7 to 9 with a mean score
      of -0.7 indicating a very small preference toward the phase-binned datasets. For
      one patient, all of the clinicians selected the amplitude binned dataset. For two
      patients, no clinicians selected the amplitude binned dataset. The mean
      percentage of responses per patient that favored the amplitude binned dataset was
      27.8% and the phase-binned dataset was 35.6%. No difference was detected in 36.7%
      of responses. CONCLUSIONS: It is not clear from our limited data that clinicians
      prefer amplitude or phase binned datasets for a random selection of lung cancer
      patients. This suggests that patients could benefit on a case-by-case basis
      depending on breathing pattern.

PMID- 28518917
TI  - SU-E-J-161: Biomechanical Framework for Thoracic Tumors Characteristics.
AB  - PURPOSE: Respiration-induced kinematics of thoracic tumors suggests a simple
      analogy with elasticity, where a strain is used to characterize the volume of
      interests. The application of the biomechanical framework allows for the
      objective determination of tumor characteristics. METHODS: The deformation of a
      given tissue element can be determined if its displacement is known. The latter
      can be obtained from 4DCT scans using image registration of the end of inhalation
      and exhalation CT volumes. The averaged right Cauchy-Green strain tensor was
      determined for each of the 15 retrospectively analyzed thoracic GTVs. The
      departure of the strain tensor from the identity matrix gauges the departure of
      the medium from rigidity. The averaging was carried out in Log-Euclidean
      framework. The fractional and geodesic anisotropy factors were determined for the
      tensor. RESULTS: The amplitude of GTV motion varied from 0.64 to 4.21 with the
      average of 1.2cm. The GTV size ranged from 5.16 to 149.99cc with the average of
      43.19cc. The tumor deformation is inconsiderable and the tensorial anisotropy is
      small. The Log-Euclidean distance of averaged strain tensors from the identity
      matrix ranged from 0.06 to 0.31 with the average of 0.19. The Frobenius distance
      from the identity matrix is similar and ranged from 0.06 to 0.35 with the average
      of 0.21. Their fractional anisotropy ranged from 0.02 to 0.12 with the average of
      0.07. Their geodesic anisotropy ranged from 0.03 to 0.16 with the average of
      0.09. These values also indicate insignificant deformation. CONCLUSION: The
      biomechanical framework allows for the quantitative description of the tissue or
      anatomical regions of interest. Such regional characterization of volume of
      interests can be used in the objective evaluation of changes of the anatomy
      during the treatment or after the treatment. It might be used for correlation of
      outcome studies with objective characterization of changes within biomechanical
      framework. These objective characteristics do not rely on human interpretation.
      The measured changes might have predictive characteristics for the therapeutic
      success of the treatment.

PMID- 28518918
TI  - SU-E-J-166: Development of Real-Time Motion Verification System for Respiratory
      Gated Radiotherapy.
AB  - PURPOSE: To develop an on-line quality assurance tool for RPM (real-time position
      management system, Varian Medical Systems, Palo Alto, CA) phase-based gated
      radiotherapy. METHODS: A real-time motion verification system (RMVS) was
      developed to verify the positional reproducibility of patient breathing between
      CT simulation and treatment. Phase-resolved anterior body midlines were extracted
      from the 4D-CT simulation data to constitute 4D reference lines. During the
      treatment, multiple infrared reflective markers attached on patient's body
      midline were tracked by a custom stereo camera system. The RPM-generated phase
      value was delivered to RMVS via in-house network communication software. The real
      time positions of tracked markers were simultaneously compared with the 4D
      reference line dynamically selected according to the phase value. The technical
      feasibility of the system was evaluated by simulating a motion phantom under
      several scenarios such as ideal case (with identical motion parameters between
      simulation and treatment; cycle = 3.1 s, baseline = 0.0 mm, amplitude = 31.0 mm),
      cycle change, baseline shift, and amplitude change. RESULTS: The developed system
      (i.e., RMVS) was fully compatible with RPM. In the phantom experiments, RMVS
      detected 5.2 +/- 1.3, 4.7 +/- 1.2, and 9.8 +/- 1.2 mm mean absolute errors (MAE)
      for -5.0, 5.0, and 10.0 mm baseline shifts, respectively. However, revealing
      about 1.0 mm MAE for both ideal and cycle change scenarios, RMVS turned out to
      have a systematic error. With 22.0, 26.0, 35.0, and 41.5 mm amplitudes, RMVS
      detected 2.3 +/- 1.3, 1.5 +/- 1.1, 2.3 +/- 1.4, and 4.9 +/- 2.5 mm MAE,
      respectively. CONCLUSIONS: The developed system demonstrated a competence for
      phase-matching error detection between real-time patient's motion and 4D-CT-based
      reference. Thus, it could be used as an on-line quality assurance tool for RPM
      phase-based radiotherapy. This work was supported in part by the SNU Brain Fusion
      Program Research Grant No. 400-20100049 (2010-2011) and the National Research
      Foundation of Korea (NRF) grant (800-20110212) funded by the Korea government
      (MEST).

PMID- 28518919
TI  - SU-E-J-177: Characterization of the Effect of 'Lung Detail' CT Reconstruction
      Algorithm on Radiation Therapy Dose Calculation.
AB  - PURPOSE: Precise tumor delineation is important in thoracic radiation therapy
      planning, and using a 'lung detail' computed tomography (CT) reconstruction
      algorithm can assist in visualizing the tumor. We seek to determine the
      dosimetric impact of utilizing a lung detail algorithm versus a standard
      algorithm on calculated dose in radiation treatment planning. METHODS: Ten
      patients, with 12 tumors, were analyzed in this study. Two CT scans, one
      reconstructed using a standard algorithm and one using a lung detail algorithm,
      were generated for each of 12 lung tumors. Treatment plans were calculated for
      each CT scan, with 7 tumors receiving stereotactic ablative radiotherapy (SABR)
      and 5 receiving intensity-modulated radiation therapy (IMRT). The Hounsfield unit
      (HU) and dose values for each voxel of the planning tumor volume (PTV),
      esophagus, spinal cord, and contralateral lung in both the CT and dose images
      were exported to MATLAB. For each contour, the voxel-by-voxel differences in the
      HU and dose distributions between the two scans were analyzed along with dose
      volume histogram (DVH) data. RESULTS: Despite changes in HU values, the voxel-by
      voxel analysis showed a negligible shift in dose values. The mean differences in
      dose for PTV, esophagus, spinal cord, and contralateral lung ranged from -12.12
      to 22.57, -2.21 to 7.40, -0.50 to 5.93, and -1.12 to 7.41 cGy, respectively. DVH
      comparisons demonstrated no meaningful difference between plans. The mean PTV,
      esophagus, spinal cord, and contralateral lung doses measured from the DVH
      shifted between plans an average of 3.5, 2.93, -0.6 and -0.35 cGy, respectively.
      These dose differences are all less than 1% of the dose prescribed to the tumor
      and are not measurable by current technology. CONCLUSIONS: The lung detail
      reconstruction algorithm, when applied to thoracic radiation treatment planning
      CT scans, can help precisely delineate tumor with negligible dosimetric impact.

PMID- 28518920
TI  - SU-E-J-170: Clinical Evaluation of Positioning Accuracy of Two Immobilization
      Devices for Stereotactic Body Radiotherapy Using Cone Beam CT.
AB  - PURPOSE: To evaluate the patient positioning accuracy and reproducibility of two
      commercially available immobilization systems for Stereotactic Body Radiotherapy
      (SBRT) treatment. METHODS: Forty one patients with lung (n=21) or liver (n=20)
      malignancies were assigned to one of the two immobilization devices: Elekta
      stereotactic body frame (SBF) with built-in stereotactic coordinate system and
      Civco modular indexing based frame (MIF) without stereotactic reference. All
      patients underwent the same simulation and planning procedure followed by cone
      beam CT (CBCT) guided treatment setup. A total of 151 CBCT images were analyzed.
      The systematic and random isocenter setup errors of the two systems were
      calculated and compared based on the daily setup corrections under CBCT guidance.
      RESULTS: There was not statistically significant difference between the two
      systems in terms of systematic setup errors in all three translational
      directions, for both lung and liver patients. The random errors for the lung
      patients under SBF setup were 1.8mm, 2.0mm and 2.9mm for the vertical,
      longitudinal and lateral directions, respectively compared to 3.6mm, 4.1mm, and
      4.2mm for MIF. A similar trend was also observed for liver patients. The random
      errors of liver MIF setup reached 3.5mm, 6.1mm and 5.7mm for the vertical,
      longitudinal and lateral directions, respectively, with relatively smaller errors
      1.7mm, 3.4mm and 2.6mm with SBF setup. Repeated CBCTs occurred for MIF system in
      42.4% and 40.7% of the lung and liver treatment to verify couch corrections based
      on the institutional tolerance, resulting in prolonged setup time. Only 25% and
      13.6% of the lung and liver treatment with SBF required with repeated CBCT.
      CONCLUSIONS: Without stereotactic coordinate reference, the body frame system
      tended to have larger random setup errors and patient positioning accuracy
      inevitably relies on the volumetric imaging guidance. Patient comfort and
      reproducibility should be clearly considered for selecting a system.

PMID- 28518921
TI  - SU-E-J-125: Uncertainty in Accumulated Dose to the Cochlea Due to Setup Error
      during External Beam Treatment of Head & Neck Cancer Patients.
AB  - PURPOSE: Treatment uncertainties are not included in modeling dose response of
      hearing loss. We determine uncertainty of accumulated dose to cochleas of head &
      neck cancer patients due to setup error during treatments of external beam IMRT.
      METHODS: We studied 8 patients: 1 planning CT for each patient and total 40 cone
      beam CTs. Those patients were treated with 33 fractions. Treatments delivered 70
      Gy to PTV, 50 to 60 Gy to nodal and sub-clinical disease using IMRT dose
      painting. Setup error was measured using 6-dimensional rigid registration between
      planning CT and cone beam scans obtained prior to treatment. Planning CTs were
      transformed and resliced to produce 'treatment CTs' according to the measured
      setup error matrix to simulate the cochlea position during treatment. We
      calculated dose delivered to cochleas at each treatment position. Treated dose to
      the cochlea from each fraction was accumulated on the planning CT using its
      registration with each 'treatment CT'. RESULTS: The RMS value of set error of
      left cochlea is 0.48pm0.28cm, right cochlea is 0.47pm0.26cm. Mean values of left
      and right cochleas are ~zero. Uncertainty in the dose to cochlea depends on each
      treatment plan and relative positions of the cochlea and target volumes. Average
      uncertainty of mean dose to cochlea is 5.0%, or 5.2cGy per fraction. CONCLUSION:
      Patient setup error introduces uncertainty to the position of the cochlea and
      consequent uncertainties in accumulated dose. Our method calculates accumulated
      dose delivered to the same cochlea volume at different treatment positions due to
      setup error. We found uncertainty in cochlea doses was 5% of planned dose after 4
      to 7 fractions. The largest uncertainty was 17 cGy per fraction. Our Results will
      be used to determine uncertainties in dose response of hearing loss in head and
      neck patients. NIH R01-CA129182.

PMID- 28518922
TI  - SU-E-J-136: Evaluation of a Non-Invasive Method on Lung Tumor Tracking.
AB  - PURPOSE: to develop a non-invasive method to track lung motion in free-breathing
      patients. METHODS: A free-breathing breathing model has been developed to use
      tidal volume and air flow rate as surrogates for lung trajectories. In this
      study, 4D CT data sets were acquired during simulation and were reconstructed
      into 10 phases. Total lung capacities were calculated from the reconstructed
      images. Continuous signals from the abdominal pneumatic belt were correlated to
      the volumes and were therefore converted into a curve of tidal volumes. Air flow
      rate were calculated as the first order derivative of the tidal volume curve.
      Lung trajectories in the 10 reconstructed images were obtained using B-Spline
      registration. Parameters of the free-breathing lung motion model were fit from
      the tidal volumes, airflow rates and lung trajectories using the simulation data.
      Patients were rescanned every week during the treatment. Prediction of lung
      trajectories from the model were given and compared to the actual positions in
      BEV. RESULTS: Trajectories of lung were predicted with residual error of 1.49mm
      at 95th percentile of all tracked points. Tracking was stable and reproducible
      over two weeks. CONCLUSION: Non-invasive tumor tracking based on a free-breathing
      lung motion model is feasible and stable over weeks.

PMID- 28518924
TI  - SU-E-J-129: Target-Specific Optimization of Four-Dimensional Cone Beam Computed
      Tomography.
AB  - PURPOSE: Undersampling artifacts are a major problem in four-dimensional cone
      beam computed tomography (4D-CBCT) and may compromise evaluation of target
      motion. The role of the target characteristics in scan parameter selection has
      not been previously investigated. In this work, we evaluated 4D-CBCT performance
      by assessing the accuracy of target motion measurements for various target sizes
      and motions. The results may serve as patient-specific guidelines for selection
      of scan parameters in 4D-CBCT. METHODS: We acquired 4D-CBCT scans of a moving
      phantom consisting of six water-filled sphere targets of sizes 10 to 37 mm, with
      various scan times ranging from 30 sec to 3 min. Two different (3-sec and 6-sec)
      periods of motions were tested. We used automatic image registration to extract
      the target motion trajectories and evaluated the accuracy of the measurement for
      the various target sizes and motions for various combinations of scan parameters.
      RESULTS: The most important object parameter to 4D-CBCT performance was the
      period of motion. Measurements for the 6-sec motion were always systematically
      less accurate than measurements for the 3-sec motion for 34 of 36 target
      sizes/motions for any given scan time. For any given target size, a 45-sec scan
      for the 3-sec motion yielded nearly equivalent accuracy to a 3-min scan for a 6
      sec motion. The second most important parameter was the target size. A 1-min scan
      was needed for sub-mm motion measurement accuracy of 28-mm target, whereas a 1.5
      min scan was needed for the 22-mm target. For all sizes and motions, temporal
      blurring was observed when the number of phases was fewer than 8. CONCLUSIONS:
      Scan time should be set according to target size and motion. We have provided
      figures that provide the minimum scan time needed to achieve the particular
      motion measurement accuracy for a particular size and period of motion.

PMID- 28518923
TI  - SU-E-J-156: Dosimetric Evaluation of Proper Width of Respiratory Gating Window
      According to Dose Distribution of EBT2 Film.
AB  - PURPOSE: We analyzed dose distribution depending on the width of gating window to
      determine the proper width of gating window in gated radiation therapy. METHODS:
      A three dimensional breathing simulator with house phantom was built to simulate
      periodic sinusoidal breathing motion of 4 seconds/cycle and 3cm fan shape
      movement. This was driven synchronized with Real-time Position Management (RPM)
      system (Varian Medical Systems, Palo Alto, CA, USA), and thereafter 4D-CT images
      were acquired. Three treatment fields (0 degrees , 120 degrees , 240 degrees )
      with gating plan using treatment planning system (Eclipse, Varian, USA) were
      performed aimed to be exposed 200cGy to isocenter. Dose evaluations regarding
      static, non-gated motion, 60% (phase of 20%-80%), 40% (phase of 30%-70%), 30%
      (phase of 40%-70%), 20% (phase of 40%-60%) and 15% (phase of 40%-55%) of gated
      motion were carried out using EBT2 film, and extents of field size, high dose
      exposed, penumbra were analyzed. RESULTS: In most cases, dose differences
      compared to static were getting decreased as the width of gating window was
      decreased. Non-gated motion showed -74.5% dose discrepancies compared to static
      exposed, whereas 15% respiratory gating window showed within 1% dose difference.
      Dose differences of 40% gating window was -30.7% whereas 30% gating window showed
      -6.3% dose discrepancies. Dose difference was rapidly reduced from 30% gating
      window against non-gated motion to 40% gating window in all cases of field size,
      high dose area, and penumbra. CONCLUSIONS: 15% respiratory gating window was
      regarded the most ideal width of gating window, but it will significantly
      increase beam delivery time over a conventional treatment. Therefore, considering
      beam delivery time and dose distributions of high dose area, field size, and
      penumbra, 30% respiratory gating window would be recommended. This work was
      supported by Nuclear Research & Development Program of the National Research
      Foundation of Korea (NRF) grant funded by the Korean government (MEST).

PMID- 28518925
TI  - SU-E-J-162: Development and Application of Internal and External Motion Tracking
      System.
AB  - PURPOSE: In this study, we performed the experiment of correlation between
      internal organ movement and external abdominal surface movement for the mini pig
      using the developed motion tracking system. METHODS: The experimental system was
      consisted with imaging acquisition part and image signal analyzing part. The
      image acquisition of internal organ was performed with a C-arm fluoroscopy
      system, and abdominal surface images were acquired with a camera and image
      acquisition board. The signal processing of the image was conducted using LabVIEW
      8.6. The developed system was applied to a mini pig. The information of the
      internal organ movement was acquired with C-arm fluoroscopy system by tracking
      the fiducial gold maker pre-implemented into diaphragm, which was used in
      Cyberknife radiation therapy. The data acquisition of internal organ movement due
      to respiration and abdominal surface movement was performed under general
      anesthesia. RESULTS: The motions of the internal and external markers were well
      correlated. The correlation coefficients between the AP movement of the external
      marker and the SI and RL movement of the internal target in the experiment using
      the mini pig were resulted in 0.903 and 0.905, respectively. CONCLUSIONS: It is
      confirmed that high correlations between the movements of external marker and the
      targetassigned in diaphragm in the experimental case for the mini pig were
      existed. Therefore, it is possible to predict the locations of internal target
      from the movement of the external marker. These results show the possibility to
      use the DTTRT (Dynamic Tumor Tracking Radiation Therapy) system of Korea
      Institute of Radiological and Medical Science (KIRAMS) to clinical application of
      animals.

PMID- 28518926
TI  - SU-E-J-140: Initial Clinical Assessment of a Gimbaled Linac Tumor Tracking System
      in a Patient Simulation Study.
AB  - PURPOSE: A simulation study was conducted on patients to evaluate the workflow
      and quantify the performance of the BrainLab/MHI Vero dynamic tumor tracking
      system in clinical circumstances. METHODS: The gimbals hold the linac-MLC
      assembly which enables tracking of moving tumors. Two kV imaging systems are
      attached at +/-45 degrees  from the 6MV beam allowing simultaneous X-rays. A
      simulation study was conducted on 5 lung-liver patients. The procedure involved
      quantification of tumor motion based on localization of Visicoil gold markers
      implanted in the tumor. Except for switching on the treatment beam, the entire
      tumor tracking workflow was executed involving patient positioning, synchronized
      acquisition of skin marker motion and X-ray images, fiducial marker detection,
      external-internal correlation model calculation, skin marker surrogate guided
      tracking and monitoring imaging. Tracking error was calculated from gimbals log
      files and the acquired monitoring X-rays. Imaging dose was measured with TLD on
      phantoms and on the patients. RESULTS: Imaging for correlation model building
      resulted in 17.6mGy skin dose. Taking the treatment duration of a 3*20Gy lung
      SBRT treatment, depending on the treatment fields orientation an additional
      maximal exposure of 28.8mGy was estimated for acquiring 1Hz X-ray monitoring
      during tracking. A mean absolute tracking error of 1.1 mm was measured, with a
      90% percentile of 2.1 mm. The average time to set up the patient entering the
      room to the first MV beam-on was 9min. From the acquisition of the modeling
      images sequence up to beam-on took 3min. CONCLUSIONS: A clinical version of the
      Vero tumor tracking system has been installed, including automatic detection of
      fiducial markers implanted in the tumor. An initial assessment has shown that the
      tracking system is functional and its performance adequate to move forward to
      final commissioning and initiation of patient treatments. This collaborative work
      was supported by the Flemish government through the Hercules foundation and the
      a?oeFonds voor Wetenschappelijk Onderzoek - Vlaanderena? grants G.0486.06 and
      G.0412.08, and corporate funding from BrainLab AG. There are no other conflicts
      of interest.

PMID- 28518927
TI  - SU-E-J-172: Development of a Video Guided Real-Time Patient Motion Monitoring
      System for Helical Tomotherpay.
AB  - PURPOSE: We developed a video image-guided real-time patient motion monitoring
      system for helical Tomotherapy (VGRPM-Tomo), and its clinical utility was
      evaluated using a motion phantom. METHODS: The VGRPM-Tomo consisted of three
      components: an image acquisition device consisting of two PC-cams, a main control
      computer with a radiation signal controller and warning system, and patient
      motion analysis software, which was developed in house. The system was designed
      for synchronization with a beam on/off trigger signal to limit operation during
      treatment time only and to enable system automation. In order to detect the
      patient motion while the couch is moving into the gantry, a reference image,
      which continuously updated its background by exponential weighting filter (EWF),
      is compared with subsequent live images using the real-time frame difference
      based analysis software. When the error range exceeds the set criteria
      (delta_movement) due to patient movement, a warning message is generated in the
      form of light and sound. The described procedure repeats automatically for each
      patient. A motion phantom, which operates by moving a distance of 0.1, 0.2, 0.5,
      and 1.0 cm for 1 and 2 sec, respectively, was used to evaluate the system
      performance at maximum couch speed (0.196 cm/sec) in a Helical Tomotherapy (HD,
      Hi-art, Tomotherapy, USA). We measured the optimal EWF factor (a) and
      delta_movement, which is the minimum distance that can be detected with this
      system, and the response time of the whole system. RESULTS: The optimal a for
      clinical use ranged from 0.85 to 0.9. The system was able to detect phantom
      motion as small as 0.2 cm with tight delta_movement, 0.1% total number of pixels
      in the reference image. The measured response time of the whole system was 0.1
      sec. CONCLUSIONS: The VGRPM-tomo can contribute to reduction of treatment error
      caused by the motion of patients and increase the accuracy of treatment dose
      delivery in HD. This work was supported by the Technology Innovation Program,
      10040362, Development of an integrated management solution for radiation therapy
      funded by the Ministry of Knowledge Economy (MKE, Korea). This idea is protected
      by a Korean patent (patent no. 10-1007367).

PMID- 28518928
TI  - SU-E-J-150: To Design a Methodology Based on Numerical Phantom for Reconstruction
      of Dose Delivered to Moving Lung Tumors.
AB  - PURPOSE: To design a methodology based on numerical phantom for reconstruction of
      dose delivered to moving lung tumors. METHODS: MatlabTM 7.6 was used to generate
      a 4D numerical lung phantom (NLP). Customer parameter files were used as input to
      this NLP, which consists of multiple ellipsoids representing body, lung, cord and
      tumor. In this study, we studied the impact of varying breathing pattern on a
      left lower lobe tumor, where the tumor motion was simulated on the daily
      breathing pattern of the patient acquired using real time positioning management
      (RPMTM) system from Varian Medical Systems. Based on the daily breathing pattern,
      the original RPM signal and the original tumor trajectory, 5 sets of motion
      trajectories were simulated. This was then used to build 10 different phases of
      the numerical phantom. Average Intensity Projection (AIP) was then generated from
      the different phases. The actual delivered dose on the 5 AIP sets were compared
      to the intended dose on the original planning AIP image set. RESULTS: The mean
      target coverage (TC) recomputed on the 5 AIP sets was approximately 18% lower
      than the TC for the planning AIP image set. The mean homogeneity index (HI)
      recomputed on the 5 sets, was approximately 5 times higher than HI for the
      planning AIP image set. The lung NTDmean dose was approximately 9.5 Gy3 and did
      not differ much. CONCLUSIONS: The presented numerical simulation framework may
      assist in monitoring the changes in dose accumulation due to changes in the
      patient's breathing on a daily basis. This can also be used for validation of new
      motion tracking algorithms and its impact of dose coverage.

PMID- 28518929
TI  - SU-E-J-122: Quantification of Respiratory-Induced Pancreatic Head Tumor Rotation
      and Deformation Using 4DCT and Fiducial Markers.
AB  - PURPOSE: To quantify pancreatic head tumor rotation and deformation due to the
      respiration using 4DCT and fiducial markers. METHODS: This study included
      seventeen pancreatic head tumor patients who were treated with gated SBRT using
      Novalis system in our institution. Each patient had two 5-mm-long fiducial
      markers placed in pancreatic head approximately 2 cm apart for the gating
      treatment. All patients had 4DCT scans of 3mm-slice thickness using a CT scanner
      (SENSATION, SIEMENS) under free breathing condition to create the internal target
      volume (ITV). The respiratory curve was generated through a pressure sensor
      placed on the patient's abdomen. The 4DCT image data sets were binned into 8
      phases: 0% inhale (end of exhale), 25% inhale, 50% inhale, 75% inhale, 100%
      inhale (end of inhale), 75% exhale, 50% exhale, and 25% exhale. The fiducial
      markers were contoured on each phase of 4DCT images, and the 3D coordinates
      (x,y,z) of centroid of the fiducial marker were recorded. The distance between
      two markers was calculated for each phase, and its variation on eight phases
      indicated the pancreatic head deformation. The orientation change of the two
      markers on eight phases indicated the pancreatic head rotation. Student t-test
      was performed for the statistical analysis. RESULTS: Pancreatic head rotation and
      deformation were observed through the breathing cycle. The largest rotation and
      deformation happened to the course from 0% inhale to 100% inahle. The rotation
      was 8.0+/-6.2 degree ranging from 2 to 20 degree. The deformation was 2.0+/-2.4
      mm ranging from 0 to 6.6 mm. Both were statistically significant with p<10-4 for
      rotation and p=0.0033 for deformation. CONCLUSIONS: The 4DCT images showed
      significant pancreatic head rotation and deformation due to respiration, and both
      rotation and deformation were highly variable between patients. For patients
      receiving SBRT with tight margin, rotation and deformation need to be considered,
      and individualized margin may be necessary.

PMID- 28518930
TI  - SU-E-J-160: 4D Dynamic Arc of Non-Modulated Variable-Dose-Rate Fields for Lung
      SBRT: A Feasibility Study.
AB  - PURPOSE: Conformal SBRT plans for Lung cancer with static gantry angles are ideal
      candidates for applying motion tracking because of: (1) better dosimetric
      conformity with reduced target margin and (2) easier and more faithful target
      tracking without intensity modulation. This work is to demonstrate that by
      delivering the target tracking during gantry rotation, we can significantly
      improve delivery efficiency without negatively affecting plan quality. METHODS: A
      lung SBRT plan with static beams was created using CT images of the reference
      breathing phase. It is converted to an arc plan with variable dose rate followed
      by the conversion to a 4D plan with the segment aperture morphing (SAM) method
      (Gui 2010) with considerations of both target location and shape changes as
      depicted by the 4D CT. Gantry angle ranges were determined from the clinical
      monitor units, with the 22.2 MU/degree, which is chosen to maximize the dose
      rate. All segments of the dynamic 4D plan were merged into a single arc with
      variable dose rate. Each segment occupying 1/10 of the breathing period delivers
      6.6 MUs at a dose rate of 1000 MU/min. Delivery time was measured and compared to
      the planned. RESULTS: The dose distributions of the single phase 3D plan and the
      arc 4D plan showed little difference. The delivered time for the 4D arc plan
      agreed with the calculated time, and is almost the same as delivering the 3D plan
      without target tracking. A 12 Gy treatment takes less than 2.5 min. CONCLUSIONS:
      The feasibility of a novel 4D delivery method where a 3D SBRT plan is converted
      into 4D arc delivery has been demonstrated. In addition to realizing the
      conventional target tracking benefits, our method further improves delivery
      efficiency, which is important for maintaining the geometric relationship between
      the target motion and the breathing surrogate during treatment. This study is
      supported by NIH_Grant_1R01CA133539-01 A2.

PMID- 28518931
TI  - SU-E-J-133: Quantitative Measurement and Modeling of Target Volume Changes by
      Respiratory Motion in CT and Cone-Beam CT.
AB  - PURPOSE: Variations in the target volume and length in CT and cone-beam CT (CBCT)
      imaging by respiratory motion were investigated for different motion amplitude
      and frequency. A model that predicts the target volume dependence on motion
      amplitude, frequency, target size, speed of CT and CBCT scanning was developed.
      METHOD AND MATERIALS: Three target volumes of differing sizes were constructed of
      tissue-equivalent gel material and embedded into artificial lung phantom.
      Respiratory motion was mimicked by a mobile phantom at a respiration frequency of
      15 cycles/min for eight different amplitudes of respiratory motion in the range 0
      20 mm. Images obtained for CT and CBCT were contoured and the target volumes and
      superior-inferior lengths were calculated. A mathematical model was developed to
      quantify and reproduce observed variations in target volumes and lengths due to
      motion artifacts. RESULTS: The measured volumes and lengths of the different
      targets increased by blurring artifacts of respiratory motion in CBCT images
      because of long scanning times (about 1 minute), which was found to enlarge
      linearly with the respiratory motion amplitude. However, in CT, the target
      volumes and lengths could increase or decrease by imaging depending on whether
      the CT scanning was parallel or opposed to the moving phantom. The mathematical
      model predicts very well the variation in target volumes imaged by CT and CBCT as
      a function of motion amplitude, frequency, target size, speed of CT and CBCT
      scanning Conclusion: The measurement and modeling of target volume and length
      variations provided quantitative assessment of induced artifacts in CBCT and CT
      imaging by respiratory motion. The modeling of imaging artifacts induced by
      respiratory motion in CT and CBCT can be used to define accurately gross tumor
      volumes and organs-at-risk which will be very useful for accurate treatment
      planning, target localization, motion tracking and beam gating during dose
      delivery.

PMID- 28518932
TI  - SU-E-J-165: Development of a Low-Cost and Clinically Available Patient
      Intrafraction Motion Monitoring System.
AB  - PURPOSE: We have developed a flexible system in order to monitor the
      intrafraction motion. The purpose of our study is to extend the monitoring system
      to clinically available system with low cost. METHODS: Our system is composed of
      a standard web camera with a low-cost and 8x magnitude telescope, a personal
      computer with our in-house software and a specific marker box. The telescopic
      lens was attached with the web camera to extend more effective distance of the
      measurement in order to avoid patient's interference. The dynamic calibration
      algorithm was developed to take into account patient's rotation during treatment
      in order to measure the intrafraction motion more accurately. Tracking three
      markers simultaneously based on a template matching technique using parallel CPU
      computing was performed to measure the intrafraction motion with dynamic
      calibration. To evaluate our new system, a respiratory motion QA phantom with 10
      mm-amplitude was used in order to measure the amplitudes under the different
      angles of web camera setting (0 to 50 degree, 5 degree step) using our system and
      Varian Real-Time Position Management Respiratory Gating (Varian-RPM) System. The
      results of our system were compared with the results of Varian-RPM System.
      RESULTS: The result of the amplitudes measured by our system and Varian RPM
      System are 10.2+/-0.3 mm and 10.3+/-0.1mm at the angle of 0 deg., respectively.
      The values of both systems were within the tolerance value of AAPM Task group
      142. The results of the amplitude of our system and Varian-RPM system were 10.2+/
      0.3mm and 10.4+/-0.1mm, respectively, while the angle was changed. Under the
      parallel CPU computing, the calculation time to measure the position of the
      marker was about 50msec including the latency. CONCLUSIONS: Our proposed system
      could have clinically acceptable accuracies. The system would be contributed
      broadly to improve the treatment accuracy because of low-cost installation of it.

PMID- 28518933
TI  - SU-E-J-176: Clinical Evaluations of a Novel Metal Artifact Reduction Technique
      for Treatment Planning in Radiation Therapy.
AB  - PURPOSE: To evaluate the effects of a CT on-board commercially available metal
      artifact reduction (MAR) algorithm for the use in radiation therapy treatment
      planning. METHODS: Phantom and clinical data were used for evaluation. A CIRS
      electron density phantom (Model 062) was scanned with Philips Brilliance BigBore
      16-slice CT simulator to establish ground truth for CT Hounsfield numbers.
      Titanium hip prostheses were subsequently inserted into the phantom to mimic
      single or double hip implants. The phantom were scanned, CT images were
      reconstructed with and without MAR correction. Dose distributions for a 6X or an
      18X beam were calculated using the three datasets and compared. CT Hounsfield
      number and variations were evaluated on both MAR-corrected and uncorrected images
      of ten clinical cases with hip implants. Dose distributions for three patients
      based on MAR-corrected images were compared to those of the uncorrected datasets
      with artifact regions density-overridden to 1.0g/cc. RESULTS: Metal artifacts
      were reduced dramatically on MAR corrected images for all phantom and patient
      cases. The phantom study indicated a remarkable improvement of Hounsfield number
      accuracy with maximum percentage difference reduction of 45% compared to the
      ground truth. CT number standard variations of the critical organs for the
      clinical cases were reduced from 30% to 66.7%. The image geometries were not
      affected by the MAR algorithm. Both critical structures and targets on clinical
      cases went from invisible to clearly visible. For all examined phantom and
      clinical cases, dosimetry difference was within 3% (mostly within 1% of the
      target volume) of the prescription dose and was not clinical significant for dose
      calculations based on different image datasets. CONCLUSIONS: The MAR algorithm
      can be safely utilized in the radiation therapy treatment planning process with
      remarkable improvements in CT number accuracy and structure conspicuity.
      Dosimetry is not highly dependent on the datasets utilized for dose calculations.

PMID- 28518935
TI  - SU-E-J-124: Assessment of Intrafraction and Interfraction Motion in Cranial SRT
      Using Tomotherapy.
AB  - PURPOSE: Stereotactic radiotherapy delivers large doses of radiation to small
      volumes with steep dose gradients, and therefore requires accurate positioning
      and near complete immobilization throughout the delivery of treatment. This work
      assesses intra and interfraction patient motion for two immobilization devices
      for patients treated on Tomotherapy. METHODS: The study set consisted of 60
      patients undergoing treatment for brain metastases over 5 fractions on MVCT
      imaged-guided Tomotherapy. Patients were immobilized using either the frameless
      Aktina PinPoint system or thermoplastic mask with bite block. To assess
      intrafraction motion, a scan was performed at the end of 2 treatment fractions.
      All MVCT Tomotherapy images were registered to the original kVCT in Amira 5.2
      using a quasi- newton, normalized mutual information affine transformation. To
      assess the precision and accuracy of MVCT image acquisition, reconstruction and
      offline Amira registration to kVCT, a phantom study was conducted. RESULTS: The
      phantom study demonstrated that the total error (noise floor) of the measurements
      and imaging/registration workflow was 0.11 +/- 0.09 mm. The Aktina frameless
      immobilization device yielded an average displacement of 2.58 +/- 2.29 mm for
      intrafraction patient motion and 2.54 +/- 1.37 mm for interfraction patient setup
      differences, while mask immobilization yielded average intrafraction patient
      motion of 1.29 +/- 1.18 mm and interfraction patient setup differences of 2.13 +/
      1.49 mm. Finally, 95% of all intrafraction motion using mask immobilization fell
      within our clinically used 2 mm margin, as compared to 75% of Aktina
      immobilization over the same margin. A margin of 3.5 mm is necessary for Aktina
      immobilized patients to include 95% of intrafraction motion within the margin.
      CONCLUSIONS: Our data indicates that mask immobilization performed better at
      preventing intrafraction motion and reducing interfraction patient setup
      differences.

PMID- 28518934
TI  - SU-E-J-169: 4D-PET for Abdominal Tumor Target Volume Generation.
AB  - PURPOSE: To examine the impact of 4D-PET on target volume delineation of upper
      abdominal tumors, versus conventional un-gated PET. METHODS: Four patients with
      upper-abdominal tumors underwent respiratory-correlated FDG PET/CT scanning (4D
      PET) as part of a continuing IRB-approved research protocol. Internal target
      volumes of FDG-avid tumors were contoured on the 4D-PET and conventional un-gated
      PET by a radiation oncologist who is a specialist in gastro-intestinal tumors. To
      create the 4D-PET ITV, the end-inhale and end-exhale 4D-PET phases were used. The
      relative volumes and volumetric overlaps of the 4D and un-gated target volumes
      were examined. Additionally, 4D-PET was used to measure the motion of the tumors.
      RESULTS: Of the four patients who were imaged, one showed minimal motion (< 3 mm
      in any direction) and one showed minimal FDG avidity; these were removed from
      further analysis. Of the two tumors which showed significant motion and FDG
      uptake, 4D-PET volumes were 28% and 21% larger than un-gated PET volumes. The un
      gated PET volumes were almost entirely contained within the 4D-PET volumes (95%
      and 93% for the two tumors). Tumors appeared to deform as well as translate with
      breathing, although this could be due to varying intra-gate motion rather than
      actual physiological deformation. The superior-inferior borders of the tumors
      exhibited the most motion, with displacements of 5.6 mm and 6.4 mm. CONCLUSIONS:
      4D-PET can be used to estimate the motion of FDG-avid upper-abdominal tumors. Use
      of 4D-PET increases the size of target volumes compared to un-gated PET in a
      subset of upper-abdominal cancer patients. Direct measurement of tumor motion and
      deformation by 4D-PET imaging could allow the use of patient-specific margins
      rather than population-based margins, potentially leading to increased target
      coverage and reduced normal tissue irradiation.

PMID- 28518936
TI  - SU-E-J-135: 3-D Fourier-Based Volumetric Registration for Estimating Intra
      Fractional Lung Tumor Motion.
AB  - PURPOSE: To develop a three-dimensional (3-D) volumetric registration algorithm
      to estimate the intra-fractional lung tumor motion between respiratory phases for
      improving the accuracy of radiotherapy treatment. METHODS: The 3-D thoracic CT
      volumes (512*512*160 voxels, with dimensions 0.97*0.97*2.5 mm3 ) in different
      respiratory phases were acquired on a General Electric Optima T580 scanner in
      cine mode. As a preprocess, a bicubic interpolation was used to interpolate the
      original 3-D volumes along the cephalo-caudal axis to volumes of size 512*512*400
      voxels, with dimensions 0.97*0.97*1 mm3 . In each respiratory phase, a sub-volume
      covering the tumor was roughly specified manually. A 3-D phase correlation of two
      sub-volumes was computed by using the 3-D inverse Fourier transformation of the
      normalized cross power spectrum of two sub-volumes. The 3-D displacements along
      three axes were estimated by finding the location of the highest peak in the 3-D
      phase correlation. RESULTS: Experiments were conducted on an artificial 4-D CT
      data set and three clinical 4-D CT data sets. Experimental results shown that the
      proposed algorithm was capable of estimating the tumor motion between respiratory
      phases with a high-accuracy (mean square error <1 mm). CONCLUSIONS: This work
      extended the conventional image registration techniques from 2-D to 3-D for tumor
      motion estimation. This work indicates a potential for significant accuracy
      improvement in radiotherapy treatment planning. The high-accurate 3-D tumor
      motion information provides a reliable basis for expanding a clinical target
      volume (CTV) to a planning target volume (PTV) to incorporate the intra
      fractional tumor motion.

PMID- 28518937
TI  - SU-E-J-146: Time Series Prediction of Lung Cancer Patients' Breathing Pattern
      Based on Nonlinear Dynamics.
AB  - PURPOSE: Prediction methods for breathing patterns, which are crucial to deal
      with system latency in treatments of moving lung tumors using state-space
      methodologies based on non-linear dynamics are contrasted to linear predictive
      methods. METHOD AND MATERIALS: In our previous work we established that breathing
      patterns can be described as a 5-6 dimensional nonlinear, stationary and
      deterministic system that exhibits sensitive dependence on initial conditions. In
      this work, nonlinear prediction methods are used to predict the short-term
      evolution of the respiratory system for 3 patients. Single step and N-point multi
      step prediction are performed for sampling rates of 5Hz, 10Hz, and 30Hz. We
      compare the employed nonlinear prediction methods with respect to prediction
      accuracy to Infinite Impulse Response (IIR) prediction filters. The simplest form
      of local prediction is finding similar segments of scalar time series data in a
      higher dimensional embedding space. Hence, we predict the future value x(t)of N
      time steps ahead by simply finding the average of nearest neighbor points to the
      point x(t) in the past and using them to estimate x(t+N), yielding a local
      average model (LAM). Local linear models (LLM) which are linear autoregressive
      models that hold only for a region around the target point formed by the nearest
      neighbor points is combined with a set of linear regularization techniques to
      solve ill-posed regression problems are also implemented. RESULTS: For all
      sampling frequencies, both single step and N-point multi step prediction results
      obtained using LAM and LLM with regularization methods are better than IIR
      prediction filters for the selected sample patients. CONCLUSIONS: The use of non
      linear prediction methods for predicting the breathing pattern of lung cancer
      patients may lead to improved, robust and accurate long-term prediction to
      account for system latencies.

PMID- 28518938
TI  - SU-E-J-155: Evaluate a Stepped TE Segmented EPI Sequence for 3D Dose Monitoring
      Using Gel Dosimetry.
AB  - PROBLEM: Gel based MR relaxometry provides accurate 3D dosimetric mapping. The
      routinely used multi spin echo (MSE) sequence has limitations. Our aim was to
      evaluate a stepped TE segmented EPI sequence for 3D dose monitoring at 1.5T and
      3T. METHODS: The polymer gel (BANG KIT, MGS Research) was prepared under normoxic
      conditions and stored in glass vials. Calibration was performed under dose range
      of 3-18 Gy with irradiation using the True Beam. Segmented Echo Planar Imaging
      Sequence was evaluated for T2 relaxometry at 1.5T and 3T (GE medical systems).
      The parameters of the stepped TE segmented Echo Planar Imaging Sequence were kept
      identical at both 1.5 and 3T: TE=15.6,27,39,51,63,75,87,99 ms; TR= 4000ms;
      FOV=22*22;Slice thk/gap: 3/3; # Shots=14; Scan time=8 min. The MSE sequence
      parameters were set close to the EPI sequence on both scanners (scan time: 18
      mins). RESULTS: The EPI image quality at 1.5 T was comparable to MSE sequence; at
      3T ghosting artifacts could be seen in EPI images. The log linear plot of signal
      intensities of the segmented EPI sequence for irradiation in the range 0-20 Gy is
      shown at 1.5 and 3T (fig 1 & 2). The T2 values agreed with that of corresponding
      MSE sequences at both 1.5 and 3Tand the fit was much better using the segmented
      EPI sequence than the MSE sequences. The dose calibration factor,a, was similar
      for all the sequences (fig. 3- 3T a: MSE=0.93, EPI=0.99; fig.4- 1.5T a: MSE=0.79,
      EPI=0.95) Conclusions: The EPI image quality at 1.5T was comparable to MSE. The
      dose calibration factor evaluated with the EPI sequences was comparable at 1.5T
      and 3T and close to the MSE sequence. Acquisition time of EPI is less than half
      of MSE sequence with more flexibility in choice of TEs .The study establishes EPI
      as a novel sequence for dose mapping.

PMID- 28518939
TI  - SU-E-J-128: Liver Motion during CBCT-Guided SBRT.
AB  - PURPOSE: Purpose of this study was to investigate the motion characteristics of
      liver during SBRT, based on fiducial markers tracked with X-ray projections of
      CBCT scans, taken immediately prior to each treatment. METHODS: Purpose of this
      study was to investigate the motion characteristics of liver during SBRT, based
      on fiducial markers tracked with X-ray projections of CBCT scans, taken
      immediately prior to each treatment. RESULTS: The range of motion for twenty
      patients were 3.00 +/- 2.04 mm, 5.08 +/- 3.12 mm and 17.93 +/- 5.11 mm in the
      planning 4DCT, and 2.77 +/- 1.6 mm, 5.29 +/- 3.10 mm and 16.46 +/- 5.69 mm in the
      treatment CBCT, for LR, AP, and CC directions, respectively. The range of
      respiratory period was 3.94 +/- 0.65 and 4.18 +/- 0.75 seconds during 4DCT
      simulation and CBCT scans, respectively. We found that breathing-induced AP and
      CC motions are highly correlated. The absolute difference in motion magnitude
      between the markers, had a positive correlation with absolute distance between
      the markers (R2=0.69, linear-fit). The inter-fractional gating window varied
      significantly for some patients, with the largest having 29.5-56.4% range between
      fractions. CONCLUSIONS: This study analyzed the liver motion characteristics of
      20 patients undergoing SBRT. A large variation in motion was observed, inter- and
      intra-fractionally, and that as the distance between the markers increased, the
      difference in the absolute range of motion also increased. This suggests that
      marker(s) in closest proximity to the target be used. This project was supported
      by Varian Medical Systems.

PMID- 28518940
TI  - SU-E-J-139: Feasibility of Using EPID for Real-Time Target Localization during
      Treatment.
AB  - PURPOSE: This study aims to investigate the feasibility of using the images of
      the treatment fields acquired by an electronic portal imaging device (EPID) for
      real-time target localization. METHODS: Forty one patients treated with IMRT and
      RapidArc were recruited in this study including 37 prostate patients and 4 lung
      patients. These patients were grouped as: prostate IMRT with lymph node (n=14),
      prostate IMRT without lymph node (n=17), prostate RapidArc (n=6), and lung IMRT
      (n=4). For each patient, two to four fiducial markers were implanted inside the
      tumor. The DRR, which projects the patient anatomy and the fiducial marker at the
      EPID location, was reconstructed for each field. The MLC aperture of each control
      point was overlay on its corresponding DRR to evaluate the fractional time when
      the fiducial marker was seen on the EPID image. The probability of seeing at
      least one, two, three, and four fiducial markers during the treatment was
      recorded. RESULTS: For the prostate IMRT patients without lymph nodes included in
      the target volume, the average probability of seeing at least one, two, three,
      and four fiducial markers during the treatment was 50% (35%-59%), 39% (23%-51%),
      24% (7%-38%), and 12% (4%-29%), respectively. For the prostate IMRT patients with
      lymph nodes, the probability was 41% (24%-51%), 29% (12%-42%), 15% (3%-24%), and
      7% (4%-15%), respectively. For prostate RapidArc treatments using two arcs, the
      average probability of seeing at least one fiducial marker was 81% (58%-90%) for
      the full arc and 74% (53%-94%) for the partial arc. For the lung IMRT treatment,
      the average probability of seeing at least one fiducial marker was 34% (20%-52%).
      CONCLUSIONS: The continuous image acquisition from the EPID during the treatment
      provides sufficient target movement information for real-time target localization
      and intrafractional target motion correction for advanced radiotherapy
      treatments.

PMID- 28518941
TI  - SU-E-J-171: Evaluation of Cervical Spine and Mandible Reproducibility of the CDR
      Mayo Mold and Civco Type-S Head and Neck Immobilization Systems.
AB  - PURPOSE: To evaluate the cervical spine (c-spine) and mandible reproducibility of
      the CDR Mayo Mold and Civco Type-S head and neck immobilization system using
      Mosaiq Setup Intelligence Curve Image Registration Methods: Patients were
      immobilized with either the Mayo Mold or Civco Type-S head and neck
      immobilization systems. Using curve image registration tools in Mosaiq, the c
      spine and mandible were outlined. For each lateral image, two separate image
      registrations were performed using an initial kV image as reference - 1) c-spine
      only 2) mandible only. To evaluate the relative difference between the c-spine
      and mandible position, the mandible image registration results were subtracted
      from the c-spine image registration results. To evaluate whether the initial
      difference between the planning CT and the first kV setup image is larger than
      subsequent daily imaging variations, the difference in the image registration of
      the DRR was compared to the variation in subsequent image registrations. The
      degree of neck flexion was determined by observing the amount of mismatch between
      the upper and lower cervical spine after the pitch correction. RESULTS: During
      the first weeks of treatment, there was minimal difference in the image
      registration results for both the c-spine and mandible individually, and in the
      relative difference between them. For neck flexion, the Mayo Mold system
      demonstrated 82.6% minimal difference and 3.8% significant difference between the
      alignment of upper and lower c spine, vs. 84% and 5.2% for the S frame. For some
      patients, there is a greater difference between the DRR and the initial kV image
      registration than the variation in registrations for subsequent daily imaging.
      CONCLUSIONS: Preliminary results indicate minimal difference in the c-spine and
      mandible reproducibility between the two immobilization systems during the first
      weeks of treatment. Further analysis of whether this minimal difference remains
      consistent throughout the entire course and treatment and with greater number of
      patients is needed.

PMID- 28518942
TI  - SU-E-J-149: Is Rotational IMRT More Susceptible to Tumor Motion than Dynamic
      IMRT?
AB  - PURPOSE: To investigate whether rotational IMRT is more susceptible to organ
      motion than IMRT that uses fixed fields. METHODS: RapidArc and sliding window
      IMRT treatment plans were each created for five lung and five pancreas cases.
      Dosimetric effects due to tumor motion were simulatedby incorporating sinusoidal
      couch motion into plans using in-house Monte Carlo dose verification software.
      Motion was emulated longitudinally (10 mm) for all cases with additional lateral
      and vertical motion (5 mm) for pancreatic tumors. Dose distributions of original
      and modified plans were compared using Gamma analysis and dose profiles. RESULTS:
      Preliminary results show that for one lung case, a 95% Gamma pass rate can be
      achieved using 6%-6-mm criterion for RapidArc versus 8%-8-mm for sliding window.
      Findings are supported by expanding on a well-known model that demonstrates the
      effects of intra-fraction motion on the delivery of dynamic intensity modulation.
      CONCLUSIONS: Rotational IMRT deliveries are believed to be no more susceptible to
      organ motion than sliding window IMRT, and results thus far support this
      conclusion.

PMID- 28518944
TI  - SU-E-J-159: Electromagnetic Tracking during 4DCT.
AB  - PURPOSE: Real-time, electromagnetic tumor tacking during 4DCT is an unsolved
      problem. The underlying problem is due to eddy current magnetic fields generated
      within the conducting surfaces in response to the source's alternating magnetic
      fields.To solve this problem, we developed a method to separate the source from
      the background fields, which can be measured with simple search coil sensors,
      such as those used by the Calypso (Seattle, WA) tracking system. METHOD: We
      modeled the environment using ANSYS Maxwell electromagnetic simulation software.
      The gantry was modeled as a 5 mm thick * 1.2 m diameter stainless-steel cylinder,
      with variable length. The transponder solenoid was modeled as a 10 mm * 1 mm
      conducting cylinder, with azimuth directed current, which was assumed to have a
      frequency range of 300-500 kHz. The search coil configuration was assumed to be a
      5 * 5 array of 5-7 cm square current loops with 6.7 cmseparation. An algorithm
      based on free space calculations and measurements was developed to calculate the
      solenoid position within the cylinder, in the presences of relatively large eddy
      magnetic fields that were generated at the same frequency as the source. RESULTS:
      Of the various methods and sensor configurations investigated, we found a method
      that localized the transponder solenoid within 1 mm over all solenoid locations
      and gantry lengths. We also found that gradient techniques did not significantly
      increase localization accuracy as expected. Complex solutions were found but not
      suitable for rapid clinical implementation. CONCLUSIONS: This method can be used
      to localize a Calypso(r) Beacon transponder during 4DCT to accurately track tumor
      positions. Furthermore, the method was based on inexpensive search coils with
      comparable dimensions to preserve the source-sensor distance. The next task is to
      create a system and investigate clinical implementation.

PMID- 28518943
TI  - SU-E-J-180: A Characterization of the LAP Aquarius Phantom for External LAP Laser
      Alignment and MR Geometric Distortion Verification for the use of SRS Patient
      Simulation.
AB  - PURPOSE: To explore additional application of the new Aquarius external laser
      alignment verification Phantom by LAP (Aq-LAP Phantom) examining geometric
      accuracy of magnetic resonance images (MRI) commonly used for planning
      intracranial stereotactic radiation surgery (ICSRS) cases. METHODS: Newly
      designed external patient alignment lasers were first aligned by the Aq-LAP
      Phantom at a Siemens Magneton Vario 3T MR unit. The scans were then performed
      with the T1 Axial 3D MPRAGE protocols with 0.9 mm temporal resolution, which may
      be used for ICSRS. They also include FLAIR, T2 BLADE and Diffusion Axial TRACE
      imaging acquisitions with 1 mm temporal resolution. The MRI will be fused to 1 mm
      cut computerized tomography (CT) images acquired by a Siemens Somatom Sensation
      Open(c). The geometric distortions (GD) were measured against the CT in all
      axial, sagital, and coronal directions at different levels. RESULTS: MR images of
      the Aquarius Phantom indicate a distinct similarity between the nonlinear GD
      along the z-axis crosshair and typical magnetic field gradient nonlinearity.
      There is linear correlation between MR divergence datasets of distorted
      crosshairs (p-values from 0.57 to 0.00), and nonlinear correlation between MR
      divergence datasets of the distorted crosshair with the CT divergence datasets of
      the cross plane (p-values from 8.45*10-4 to 1.38*10-46). The margin of error
      exceeded no more than 0.29 mm. GDs up to about 2 mm are observed at the distal
      regions of the longitudinal axis in the SRS treatment planning MR images.
      CONCLUSIONS: Using the Aquarius Phantom, one is able to detect GD in ICSRS
      planning MRI acquisitions, and align the external LAP patient alignment lasers by
      following the LAP QA. Based on the results, one may recommend using the Aquarius
      Phantom to determine if margins should be included for SRS treatment planning.
      The Aquarius Phantom, used for laser alignment and geometric distortion
      detection, was provided by LAP of America.

PMID- 28518945
TI  - SU-E-J-132: Quantitative Assessment of CT Number Variation Induced by Respiratory
      Motion Artifacts in CT and Cone-Beam CT.
AB  - PURPOSE: CT number variations due to image artifacts induced by respiratory
      motion in CT and cone-beam CT (CBCT) imaging were investigated. A model was
      developed to predict CT number variations observed in CT and CBCT images. METHOD
      AND MATERIALS: Three target volumes of differing sizes were constructed of tissue
      equivalent gel material and embedded into an artificial lung phantom. This mobile
      phantom mimicked respiratory motion with eight different amplitudes of
      respiratory motion in the range 0-20 mm at a frequency of 15 cycles/min. A model
      was developed allowing for simulation of the observed CT number variation as a
      function of the target volume, phantom motion frequency and amplitude and speed
      of CT scanning. The simulation results were compared quantitatively with CT
      profiles that were obtained from CT and CBCT imaging. RESULTS: The size and
      distribution of CT numbers of well-defined homogenous targets varied with
      respiratory motion. In CBCT, CT number variations depends mainly on the target
      size and motion amplitude. Targets with a dimension smaller than the motion
      amplitude show highest CT number densities at the edges of the elongated volume.
      Conversely, targets larger than motion amplitude showed greatest CT number
      densities in the middle of the target. In CT imaging, CT number variations were
      more complicated and further depends on the speed of CT scanning where some
      targets were elongated or shrunk with varying CT number gradients depending on
      the above parameters. CONCLUSION: The sizes and CT number distributions varied
      with motion for the homogenous targets. The CT number variations were modeled and
      simulation provided comparable distributions to those observed in CT and CBCT
      images based on target size, amplitude, frequency, and scanning speed. The
      results here might provide useful tools to correct image artifacts and consider
      CT number variation due to motion in treatment planning and dose delivery.

PMID- 28518946
TI  - SU-E-J-164: Verification of Commercial Respiratory Tracking System Using
      Scintillation Screen.
AB  - PURPOSE: The accuracy of the tracking system is critical for the result of four
      dimensional radiation therapy. The objective of this study is to propose the
      method of verifying the accuracy of respiratory tracking system. METHODS: The
      scintillation screen and the light marker between the transparent acrylic plates
      were designed to move according to the prerecorded respiratory organ motion of
      volunteers. A vertical circle photon beam with 3 cm diameters from the cyberknife
      unit was planned to track the motion of the scintillation screen with the plates.
      In dark room, the CCD camera outside of the phantom captured the scintillation
      from the screen and the light marker in 30 frames per second when the photon beam
      was incident. The pictures were captured by the CCD camera were analyzed frame by
      frame, and the discrepancy between the scintillating circle on the scintillation
      screen and the light marker depending on the time was measured. The discrepancy
      of the motions of the delivered photon beam and the light marker was analyzed.
      RESULTS: In the preliminary study, the maximum discrepancy was measured less than
      1.5 mm in normal breathing pattern as the manufacturer specified it. CONCLUSIONS:
      As the speed of the motion was increased, the discrepancy between the position of
      the beam and internal marker increased. However, the error was clinically
      acceptable. The further study will be performed for the irregular respiratory
      motion patterns. This research was supported by Basic Science Research Program
      through the National Research Foundation of Korea (NRF) funded by the Ministry of
      Education, Science and Technology (20110004848).

PMID- 28518947
TI  - SU-E-J-143: Characteristics of Tumor-Motion Surrogate Signals Analyzed Using
      Empirical Mode Decomposition and Hilbert-Huang Transformation.
AB  - PURPOSE: We introduce a novel technique for analyzing tumor-motion surrogate
      signals using Empirical Mode Decomposition (EMD) and Hilbert-Huang Transformation
      (HHT). METHODS: The tumor-motion surrogate signals were acquired (with
      RPM/Varian), from 20 lung-cancer patients in free-breathing method and its data
      were decomposed into Intrinsic Mode Functions (IMFs) using EMD. HHT was then
      applied to each IMF to obtain instantaneous frequency as a function of time. The
      Result of the frequency information was compared to Fast Fourier Transformation
      (FFT) and manual calculation of frequency. Correlation of each IMF with the
      surrogate signal was used to determine the adequate IMF as a faithful tumor
      motion surrogate. RESULTS: The surrogate RPM signals were decomposed to 10 +/- 1
      IMFs on average. The decomposed IMFs showed three categories of frequencies: (1)
      high frequencies (1 - 10 Hz) such as a noise-like signal, (2) medium frequencies
      (0.1 - 0.3 Hz), which is potentially a true breathing signal, and (3) low
      frequencies (0.003 - 0.09 Hz), which behave a baseline drift. The marginal
      frequency, which is a measure of total amplitude contribution from each
      frequency, showed an average difference of -0.03 +/- 0.07 from the FFT and -0.02
      +/- 0.05 with the manual calculations. Each surrogate signal showed a high
      correlation with one IMF (0.747 on average) and, a low correlation with the rest
      of the IMFs (0.139 on average). The IMF with a high correlation alone represented
      the surrogate signal well in terms of breathing frequency and amplitude.
      CONCLUSIONS: The EMD and HHT were used to analyze the cyclic components of
      nonlinear and non-stationary surrogate signals in the time domain. Since the EMD
      decomposes the signal into physically-meaningful modes, it was possible to
      determine IMFs that represent the tumor motion faithfully after removing noise
      like signals. Further investigation on physical meanings of the IMFs is the next
      step of the study.

PMID- 28518948
TI  - SU-E-J-175: A Patient-Specific 4D Digital Phantom for Dynamic Dose Estimation of
      External Ionizing Radiation.
AB  - PURPOSE: To develop a realistic yet flexible 4D digital phantom based on patient
      anatomy for dynamic estimation of organ doses due to external ionizing radiation.
      METHODS: In this work, we propose to build a 4D digital phantom based on patient
      CT anatomy and time-tagged CT information. A regional 4D-CT is first acquired on
      the patient around lesion with a RPM system. By binning CT information at various
      phases of respiratory motion, we can create a regional 4D phantom. By applying
      non-uniform rational B-spline (NURBS) surface technology, we can easily
      accommodate the size-specific and gender-specific differences in the organ shapes
      and body contours, often observed during a long course of radiotherapy
      treatments. Based on the ICRP reference phantoms, we can extend the patient
      specific 4D regional phantom into a 4D whole-body phantom unique to each patient.
      The resultant 4D phantom will serve as the digital representative of the patient
      himself or herself in the virtual environment and is ready for Monte Carlo
      particle transport. RESULTS: Considering the newborn skin thickness (0.663 mm),
      0.5 mm is defined as the maximum voxel resolution available in our 4D digital
      phantom. The resultant 4D digital phantom is essentially a high-resolution voxel
      phantom (with voxel dimensions down to 0.5 mm * 0.5 mm * 0.5 mm) capable of non
      uniform scaling of organs and body contours based on NURBS surface technology.
      CONCLUSIONS: It is feasible to build a 4D patient-specific digital phantom
      suitable for Monte Carlo radiation transport simulation. With a digital phantom
      for each patient, an accurate estimation of the organ doses in 4D will be made
      possible, which will contribute to a better tumor control because of the detailed
      knowledge of dose distributions in patient anatomy not only spatially but also
      temporally. The proposed 4D phantom will also allow for deformable dose
      registration for adaptive radiotherapy.

PMID- 28518949
TI  - SU-E-J-168: 4D-PET for Target Volume Delineation in Respiratory-Gated Radiation
      Therapy.
AB  - PURPOSE: To find an optimized workflow for the use of respiratory-gated PET (4D
      PET) in target volume delineation of tumors subject to respiratory-gated
      radiation therapy. METHODS: 15 patients with lung (11) and pancreas (4) tumors
      who had FDG-PET-CT for target delineation prior to EBRT were studied. Patients
      were selected among the group that showed respiratory-induced tumor motion >5mm.
      4D-PET was performed by means of a Philips Gemini BigBore scanner, using the
      Varian RPM gating system. An identical system was available at the linac for
      treatment. The breathing cycle was equally divided in 4 phases, according to a
      previous study. Since planning was made on a single CT-phase, no ITV was
      explicitly built from the set of phases. The BTV was identified with SUV=2.2
      threshold and the PTV was obtained expanding the BTV by 8mm(S-I), 5mm(A-P) and
      3mm(L-R) to account for residual motion and setup errors. The most advantageous
      CT-phase for treatment planning was then identified by simulating plans on each
      phase and analyzing the resulting DVHs of OARs (lung, trachea, oesophagus, spinal
      cord, left ventricle). RESULTS: The observed maximum range of motion was 5.5mm(L
      R), 12.3mm(A-P) and 19.2mm(S-I). The standard deviation of the BTV volume in the
      4 phases ranged from 6% to 13.7%. V20 (lung) ranged 7.1%-15.2% in inspiration and
      7.8%-18.6% in expiration. The mean dose to the oesophagus ranged 0.1-2.2Gy in
      inspiration and 1.4-2.0Gy in expiration. In general, the dose to OARs was smaller
      when planning on a single phase than on the overall, respiratory-uncontrolled
      volume (p-value<0.05). CONCLUSIONS: The BTV volume was almost constant between
      phases, confirming that the motion might be described by 4 phases. There was no
      obvious choice of the optimal phase for treatment planning, suggesting patient-by
      patient studies. However, planning and delivery on one phase consistently allowed
      dose sparing to be obtained compared to non-gated techniques.

PMID- 28519009
TI  - SU-E-J-189: The Kullback-Leiber Divergence for Quantifying Changes in
      Radiotherapy Treatment Response.
AB  - PURPOSE: Repeated imaging is an extremely powerful tool in current radiotherapy
      practice since it allows advanced tumor detection and personalized treatment
      assessment by quantify tumor response. Change detection algorithms have been
      developed for remote sensing images to mathematically quantify relevant
      modifications occurring between datasets of the same subject acquired at
      different times. We propose usage of change detectors in radiotherapy for an
      automated quantification of clinical changes occurring in repeated imaging.
      METHODS: We explore usage of the Kullback-Leiber divergence as indicator of tumor
      change and quantification of treatment response. The Kullbach-Leiber divergence
      uses the likelihood theory to measures the distance between two statistical
      distributions and thus does not assume consistency in imaging. By it's general
      nature, it can accommodate the presence of noise and variations in imaging
      acquisition parameters that usually hinder automated identification of clinically
      relevant features. RESULTS: In a comparison of simple difference maps and the
      Kullbach-Leiber divergence operator, the difference maps were affected by noise
      and did not consistently detect changes of low intensity. In contrast, the
      proposed operator discerned noise by considering regional statistics around each
      voxel, and marked both regions with low and high contrast changes. CONCLUSIONS:
      Statistical comparison through Kullback-Leiber divergence provides a reliable
      means to automatically quantify changes in repeated radiotherapy imaging.

PMID- 28519011
TI  - SU-E-J-201: What is the Importance of Dose Recalculation for Adaptive
      Radiotherapy Dose Assessment?
AB  - PURPOSE: To quantify the effect of using the planned dose distributions in lieu
      of performing dose recalculations on daily in-room images for adaptive
      radiotherapy (ART) dose assessment of head and neck cancer patients. METHODS: 16
      patients with cancers of the head and neck were treated using the TomoTherapy Hi
      Art II (Accuray Inc., Sunnyvale, CA). Images of all patients were acquired prior
      to each treatment using the megavoltage CT (MVCT) capability of the TomoTherapy
      unit. Overall, images from 528 fractions were evaluated. For every image set, the
      delivered dose was estimated by both recalculating the dose distribution using
      the acquired MVCT and also by simply overlaying the planned distribution on the
      new images. ART dose assessment was performed using deformable image registration
      (DIR) to deform contours from the treatment plan to the images acquired during
      each fraction and to accumulate the estimated dose delivered during each fraction
      back to the reference treatment plan. The same DIR maps were applied to both dose
      estimation methods. Dosimetric endpoints were then compared between the DVHs
      computed using the recalculated or planned dose distributions. RESULTS: The mean
      PTV D95% and D05% endpoints were 0.6+/-0.5% and 1.4+/-0.8% lower using the
      planned dose distributions compared to the recalculated distributions,
      respectively, across all patients. The mean parotid D50% was 2.4+/-1.5% greater
      using the planned distributions compared to the recalculated distributions. The
      parotid D50% from the planned distributions was also highly correlated with the
      parotid D50% from the recalculated distributions for each patient (mean r2=0.97+/
      0.09). CONCLUSIONS: For this treatment modality and site, dosimetric differences
      observed between overlaying the planned dose distributions and recalculating
      distributions on daily images were typically well within +/-5%. This indicates
      that the dose distribution itself is robust against anatomic variations. This
      study was funded, in part, by a grant from Accuray Inc.

PMID- 28519010
TI  - SU-E-T-16: Statistical Variability and Confidence Intervals for Planar Dose QA
      Pass Rates.
AB  - PURPOSE: The most common metric for comparing measured to calculated dose planes
      is a pass rate generated using percent difference, distance-to-agreement (DTA),
      or some combination of the two (e.g. gamma evaluation). The grid of analyzed
      points often corresponds to a dosimeter array with low areal-density of point
      detectors. This work examines the statistical uncertainty of planar dose
      comparison pass rates and proposes methods for establishing confidence intervals
      for pass rates obtained with low detector-density arrays. METHODS: Absolute dose
      planes were acquired via EPID for twenty intensity-modulated fields of varying
      complexity. Matching calculated dose planes were created via treatment planning
      system. Pass rates for each dose plane pair (centered to CAX) were calculated
      with various %/DTA composite analysis techniques. Software was designed to
      selectively sample the high-density EPID matrix to simulate many low-density
      measured grids, each representing a different alignment with respect to CAX.
      Simulations were repeated (100 positional iterations per field) using grids of
      varying detector-densities and both random and orthogonal point-detector
      orientation. For each simulation, pass rates were calculated with various
      composite analysis techniques. RESULTS: Repositioning simulated low-density grids
      leads to a distribution of possible pass rates for each measured/calculated dose
      plane pair, independent of whether the detector grid is random or uniform.
      Distributions can be predicted using a binomial distribution by which a
      confidence interval (function of sampling density and observed pass rate) is
      approximated for each pass rate. For example, 95% confidence intervals for IMRT
      pass rates (2%,2mm) average +/-5.3% and +/-3.8% with 1-detector/cm2 and 2
      detector/cm2 grids, respectively. CONCLUSIONS: Pass rates for low-density array
      measurements are not absolute and should be reported with both a full description
      of calculation method and confidence intervals quantifying their uncertainty.
      Results extend to 3D detector arrays. The concept of fixed 'action levels' for
      pass rates must be reexamined for low-density array measurements.

PMID- 28519012
TI  - SU-E-T-26: Evaluation of New Pre-Treatment In-Air Patient Specific QA Software
      for TomoTherapy Treatments.
AB  - PURPOSE: Math Resolutions, LLC, has extended their Dosimetry Check quality
      assurance software to include TomoTherapy treatments. Data collected from
      TomoTherapy's MVCT detectors is processed and compared to the planned treatment
      dose allowing for pre-treatment QA without the use of phantoms and other
      detectors. This study presents an overview of our experience at the University of
      Virginia developing, implementing, and verifying this novel QA strategy. METHODS:
      Low modulation and high modulation cheese phantom plans as well as patient plans
      (prostate, GYN, and vertebra) were used to test the Dosimetry Check in-air
      software. For all evaluations the treatment table was removed from the XML file
      of each plan using software provided by Accuray and the resulting in-air
      calibration plan was delivered. The exit detector sinogram was extracted from the
      machine and imported into Dosimetry Check along with the TomoTherapy calculated
      planned dose. The fluence maps were reconstructed and used to recalculate the
      dose. RESULTS: The percent difference between the planned dose and the dose
      calculated from the exit detectors by Dosimetry Check ranged between 0.62% for a
      simple low modulation cheese phantom plan with a cylindrical target to 7.3% for a
      high modulation 2.5cm prostate plan. The gamma indices reported range from 94.7%
      to 97.8% <1 over the overall calculation area for the plans tested using a gamma
      of 3% and 3mm. For the area receiving over 80% of the prescribed dose, the gamma
      ranged from 80.7% to 92.9% <1. CONCLUSIONS: The results of our investigation of
      Math Resolutions' new product in development, Dosimetry Check's pre-treatment in
      air QA software, demonstrate that it has the potential be a very useful and
      practical tool for TomoTherapy QA. Further testing is being performed in which
      various errors are intentionally introduced in the delivered dose to test the
      limits of Dosimetry Check's sensitivity. Research Grant from Math Resolutions LLC
      01/12/2012-01/11/2013 Math Resolutionsa?TM Dosimetry Check software was given to
      UVa to assist with evaluating the precision of the product in reconstructing dose
      from the TomoTherapy exit detector data.

PMID- 28519013
TI  - SU-E-J-212: Real-Time Treatment Failure Detection for Moving Tumor with Image
      Guidance.
AB  - PURPOSE: Respiratory motion can cause misalignment of the radiation beam and will
      greatly degrade the effectiveness of cancer radiation treatment. Failure of
      radiation treatment can be detected by real-time image. The efficiency of both
      internal tracking and external tracking has been assessed in this. METHODS: Both
      3D internal fiducial marker motion and 1D external abdominal surface motion data
      of 11 patients were collected simultaneously. Linear and quadratic functions have
      been applied to correlate the internal and external motion signal. To detect
      tracking failure of external imaging, three approaches have been proposed: (i)
      correlation only: which will compare directly between the tracked and the based
      curve. (2) fixed baseline shift: which interferes the treatment by adjusting the
      baseline of tracked signal to compensate target motion for each treatment
      fraction. (3) dynamic baseline shift: dynamically interfere with treatment for
      each breathing cycle. (4) dynamic baseline with base curve update, is the third
      approach with base curve for each fraction. RESULTS: Generally, the quadratic
      function produced better correlation results than the linear correlation. With
      more historical data available, the quadratic prediction gives better correlation
      outcomes. The tracking frequency of 30, 10, 5, 2, 1, and 0.2Hz has been
      evaluated. Although high imaging frequency usually results in better correlation,
      imaging rate of 1 Hz will results acceptable results. For the failure detection,
      the average Euclidean misalignment is 3.46, 2.42, 2.21, 1.80 for the above four
      approach. With treatment interference, the beam-on-time percentages are 54.03,
      58.26, 63.94, and 60.48 respectively. CONCLUSION: High imaging frequency is not
      required. approaches with baseline shift and base curve update will improve the
      treatment efficiency and treatment accuracy. Guidance using hybrid imaging with
      high-frequency of external imaging and low internal imaging is needed to
      compensate tumor respiratory motion.

PMID- 28519014
TI  - SU-E-J-182: Patient Specific Assessment of External Radiation Exposure to
      Bystanders Interacting with Patients Following 131I Therapy.
AB  - PURPOSE: Conventional calculation methods of patient release criteria for
      compliance with NRC regulations are based on the assumption that both patient and
      bystander are each a single point in space. This study was intended to assess the
      patient-specific external radiation exposure to a bystander interacting with the
      patient following radionuclide therapy with 131I. METHODS: 131I-sodium iodide
      treatment for hyperthyroidism and thyroid cancer and 131I-tositumomab treatment
      of non-Hodgkin's lymphoma were considered. 131I distribution provided by the
      patient SPECT image was rendered on the SPECT-fused CT images. The CT images were
      then imported to a Monte Carlo based simulation code, MCNPX 2.7, as a source
      phantom. For a target phantom, we employed the adult male hybrid phantom
      developed at the University of Florida and National Cancer Institute. A single
      orientation - patient and a bystander facing one another at 1.0 m - was
      considered. S factors (dose per unit cumulative activity (A)) for each organ in a
      bystander was obtained from the MC calculations and effective dose (EDE) per A
      was calculated based on tissue-weighted individual organ doses. The results were
      compared with the calculations using UF/NCI adult hybrid source/target phantoms
      and the revised adult ORNL stylized source/target phantoms. RESULTS: EDE per A of
      the stylized phantom was 1.5% higher than that of the hybrid phantom for uniform
      source localization in the thyroid. However, EDE per A of the hybrid phantom was
      20% less than that of stylized phantoms for a torso source. The difference is
      attributed to the realistic shape of the frontal body comparing to the simple
      ellipsoidal trunk of the stylized phantom. CONCLUSIONS: Based on the realistic
      hybrid phantoms and accurate MC radiation transport calculation tools, patient
      specific dosimetry for a bystander is feasible. S factors will be calculated
      using the patient CT image with 131I bio-distributions and hybrid phantoms.

PMID- 28519015
TI  - SU-E-T-09: Empirical Evidence for Decreased Cell Survival in Flattening Filter
      Free Beams.
AB  - PURPOSE: To present empirical evidence for a decrease in cell survival with the
      introduction of markedly increased average dose rates in flattening filter free
      beams. METHODS: Data of (Bewes et al., 2008) are used to calculate a modification
      factor for cell survival curves, using the linear quadratic model, that is
      inversely proportional to the reciprocal of the average dose rate. RESULTS: The
      survival curve becomes steeper as the average dose rate increases above a ~600
      cGy/min threshold. For average dose rates below this threshold, no significant
      effect or even an increase in cell survival was observed (as explained by the Lea
      Catcheside dose protraction factor). For a maximum assumed dose modification
      factor of 1.2 a decrease in cell survival of 3.5% for a dose of 2Gy and 36% for a
      dose of 8 Gy is predicted for a MM576 cell line. For a maximum assumed dose
      modification factor of 1.4 a decrease in cell survival of 60% for a dose of 2Gy
      and 1 order of magnitude for a dose of 8 Gy is predicted for a NCI-H460 cell
      line. For a dose modification factor of 2.65 with a dose rate of 24 Gy/min, a
      decrease in cell survival of 1 order of magnitude at 2Gy and 5 orders of
      magnitude at 8 Gy is predicted for a NCI-H460 cell line if it is assumed that the
      inverse proportionality is true. CONCLUSION: Although no effects on cell survival
      was seen previously with clinically achievable dose rates (except for enhanced
      cell survival through repair for increased treatment times), it might become more
      evident with the increase of the average dose rate in flattening filter free
      beams. This will necessitate revision of fractionation schemes and maximum
      tolerable doses for organs at risk for stereotactic body radiation therapy.

PMID- 28519016
TI  - SU-E-J-193: Gamma Knife Perfexion End-To-End Testing with a Commercial
      Stereotactic Phantom.
AB  - PURPOSE: To investigate the use of the Lucy (r) Stereotactic Phantom (Standard
      Imaging, Inc.) for Gamma Knife Perfexion radiosurgery quality assurance of the
      imaging, treatment planning, and dose delivery processes. End-to-end testing of
      the Perfexion and Gamma Plan version 10.1 has not been previously examined in
      literature. METHODS: The phantom was imaged using both the CT and T1- and T2
      weighted MR sequences used for treatment planning. For imaging, the isocentric
      volume insert and fiducial markers were positioned within the phantom. Scans were
      transferred to the Gamma Plan treatment planning system and were evaluated for
      geometric and fusion accuracy. A plan was created to deliver 12Gy to the 50%
      isodose line to the 5.25cm3 volume. During dose delivery, Gafchromic EBT2 film
      was positioned in the film insert to replicate the position of the target volume.
      Dose results were analyzed using RIT software (Radiologic Imaging Technology,
      Inc.). RESULTS: Image fusion integrity was inspected by overlaying the MR and CT
      markers (5 fiducial markers spaced 5mm apart) and visually examining the
      resulting volume insert overlap between the three scans. Geometric accuracy was
      evaluated by contouring three volumes using Gamma Plan contouring tools.
      Agreement within 1.1%, 6.7% and 12.2% of the actual volumes was seen with the T1
      weighted, T2-weighted, and CT images, respectively. The volume-based acquisition
      and 1mm slice thickness of the T1-weighted sequence resulted in the most accurate
      measurement. Geometric measurements along two dimensions showed acceptable
      accuracy for all imaging modalities within 1.6%. Dosimetry results agreed well
      with the planned dose. The EBT2 film was calibrated for absolute dose
      measurements using a dose calibration curve for 0.1-30 Gy and the calibration
      curve was verified to have <3% error above 1Gy. CONCLUSIONS: The Lucy phantom
      allows for comprehensive quality assurance testing of the Gamma Knife Perfexion
      radiosurgery process.

PMID- 28519017
TI  - SU-E-T-20: Removal of Electron Contamination in Longitudinal Field MRI-Linac
      Systems: A Monte Carlo Study.
AB  - PURPOSE: The prototype inline MRI-linac system has some advantages over
      perpendicular models including avoiding the electron return effect. One of the
      disadvantages of the inline approach is the increased skin dose, estimated to be
      400-1000% of the dmax dose. The purpose of this work was to design a feasible
      method to reduce this skin dose to acceptable levels. METHODS: Magnetic modeling
      of proposed MRI-linac designs have been simulated with the inclusion of an
      optimized permanent magnet system to purge/deflect the electron contamination.
      The region of air above the phantom was also replaced with a helium bag (region
      of helium gas) and a beam scrapper below the deflector was added to collect
      deflected off-axis contamination. Monte Carlo simulations were then performed
      including the accurate 3D magnetic field maps. Surface dosimetry was recorded to
      verify the changes to the skin doses. RESULTS: Magnetic modelling showed that an
      optimized NdFeB permanent magnet system located outside the MRI coils (below the
      MLC's) can provide a strong enough region to purge/deflect a significant portion
      of the electron contamination from the x-ray beam. The impact on the MRI
      uniformity is around 100 ppm and hence is correctable via active/passive shimming
      of the MRI. The helium region also significantly limits the production of
      contamination traveling towards the phantom surface. Entry doses near CAX are
      predicted to be similar to the 0 T case. CONCLUSIONS: Magnetic and Monte Carlo
      modeling were performed to estimate the effect that a permanent magnet purging
      system, beam scrapper, and helium bag would have on lowering the skin doses in an
      inline MRI-Linac system. MRI non-uniformities introduced by the deflector could
      be corrected, contamination is mostly purged or blocked, and the helium bag
      minimizes air-generated contamination. As a result skin doses are comparable to
      having zero magnetic field.

PMID- 28519018
TI  - SU-E-J-205: Modeling Fiducial Marker Movement in Prostate.
AB  - PURPOSE: To understand fiducial marker movement in prostate and to improve
      prostate patient positioning with fiducial markers. METHODS: Patient planning CT
      and positioning CBCT were retrospectively analyzed. CBCT images were
      automatically registered to the corresponding CT ones based on their bony
      structures in Eclipse. The coordinates of the markers in the CT and CBCT were
      recorded. The status of bladder and rectum fillings, and gas in rectum were
      indexed into four levels and recorded. An algorithm was developed to optimally
      register the (three) fiducial markers in CBCT with those in the CT so that only
      the information on prostate deformation and marker migration remained. A
      mathematical model was built to estimate the marker migration and the relative
      contribution to the deformation from the status change of bladder and rectum.
      RESULTS: The registration error from our optimal registration algorithm indicates
      the minimal patient setup error by using fiducial markers. The results from our
      analyzed 3 patients were average(standard deviation) = 1.10(0.40), 1.27(0.67) and
      0.62(0.38) mm, but there were some fractions when the registration errors were
      over 2 mm. From our mathematical model, it was found that the marker migration
      could be as large as 2.9 mm. If 2 mm tolerance is required in such as SBRT, then
      soft tissue based registration may be more appreciated when the optimal
      registration error is greater than 2 mm or from the date when the migration is
      greater than 2 mm because the migrated marker may not change the location
      thereafter. In addition, for one investigated patient, the relative contribution
      to the deformation from the bladder, rectum filling and gas in the rectum is
      0.43:0.31:0.26. More patient data are in analysis, and other interesting results
      will be reported. CONCLUSIONS: Fiducial marker migration can be over 2 mm. The
      migration will Result in a conclusion that small registration error does not mean
      good patient positioning.

PMID- 28519019
TI  - SU-E-T-02: Radiobiological Comparison of Two Treatment Schemas in IMRT Prostate
      Radiotherapy.
AB  - PURPOSE: Different fractionation schemas are used for the treatment of prostate
      with IMRT. Due to the low alpha/beta of prostate hypofractionated schemas are
      achieving more importance. The purpose of this study is to compare two IMRT
      techniques from a radiobiological point of view in the treatment of high risk
      prostate cancer, the sequential IMRT technique (SIMRT) and a simultaneous
      integrated boost IMRT treatment (SIBIMRT). METHODS: 20 patients were selected and
      planned using both treatment strategies to give an EQD2 of 82 Gy to prostate, 70
      Gy to vesicles and 46 Gy to lymph nodes, using the linear quadratic model LQ
      supposing an alpha/beta prostate=1.5 Gy. Dose volume histograms of prostate,
      rectum and bladder were calculated. Tumour Control Probabilities (TCP) and Normal
      Tissue Complication Probabilities (NTCP) were also calculated. As the prostate
      alpha/beta is not known exactly the TCP has been calculated for different
      a/bprostate values ranging from 1.5 to 10 Gy. NTCPs of bladder and rectum were
      calculated also for alpha/beta oar values ranging between 1 to 15 Gy. RESULTS:
      Both treatment strategies were found to be equivalent in terms of prostate ptv
      TCP and EQD2 for low alpha/beta prostate=1.5 Gy. In the case of high alpha/beta
      prostate values, 3 Gy and 10 Gy, EQD2 and TCP for prostate ptv are lower for the
      SIBIMRT technique. For rectum and bladder, if a/boar ranges between 2 and 15 Gy
      EQD2 values are higher for the SIMRT treatment schema. NTCP for bladder and
      rectum is higher for the SIMRT technique when alpha/beta OAR >= 2 -3 Gy.
      CONCLUSIONS: In this study a comparison between two treatments strategies have
      been done. Our results show that a hypofractionated technique for high risk
      prostate cancer reduces, or equals, EQD2 and NTCP for bladder and rectum while
      maintaining the TCP of prostate for the typical alpha/beta values in use.

PMID- 28519020
TI  - SU-E-J-186: CT Textures Can be Predictive for Tumor Shrinkage.
AB  - PURPOSE: To determine if NSCLC GTV CT textures can be predictive for tumor
      shrinkage after proton therapy with concurrent chemotherapy. METHODS: Simulation
      and weekly 4DCTs were obtained from 25 patients with locally advanced NSCLC
      treated by proton therapy at a 74 Gy dose level with concurrent chemotherapy. In
      house deformable image registration software based on the demons algorithm
      propagated the physician-generated planning GTV onto each weekly image set. GTV
      soft tissue volumes were then extracted from CT images by in-house software which
      pruned out voxels below a cutoff HU threshold. Patients whose normalized end
      treatment pruned GTV was less than the group median were classified as 'strong
      responders.'The remaining patients were classified as 'weak responders.' For each
      pruned GTV, the MaZda texture analysis software generated quantitative 3D texture
      features based on the image histogram, absolute gradient, co-occurrence matrix,
      and run-length matrix. Using the Fisher coefficient, a subset of these texture
      features that were relevant to distinguishing the two response groups was
      obtained. In-house software and MaZda were then used to perform neural network
      data classification with leave-one-out cross-validation based on this texture
      feature subset. The true positive rate (TPR), false positive rate (FPR),
      classification accuracy, and one-sided p-values were recorded. RESULTS: Six
      classification models were tested. Each model had a unique combination of feature
      extraction and analysis parameters. Taking 'strong responders' to be the
      'positive' class, the average TPR was 0.66 (0.60 - 0.75), the average FPR was
      0.36 (0.31 - 0.40), the average classification accuracy was 64.8% (60.0% -
      68.0%), and the average one-sided p-value was 0.118 (0.055 - 0.215). CONCLUSIONS:
      There is some evidence showing that NSCLC GTV CT textures can be predictive for
      tumor shrinkage after proton therapy. Further work should be done to include more
      patients, texture metrics, and data analysis techniques. The presenting author
      receives funding support from a Hertz Foundation Applied Science Fellowship.

PMID- 28519021
TI  - SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9
      Radioactive Eye Plaque Using MCNP5.
AB  - PURPOSE: To show the effect of gold backing on dose rates for the USC #9
      radioactive eye plaque. METHODS: An I125 source (IsoAid model IAI-125A) and gold
      backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was
      simulated with and without gold backing. Dose rates were calculated in two
      orthogonal planes. Dose calculation points were structured in two orthogonal
      planes that bisect the center of the source. A 2*2 cm matrix of spherical points
      of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion
      particle histories were tracked. Dose differences with and without the gold
      backing were analyzed using Matlab. RESULTS: The gold backing produced a 3%
      increase in the dose rate near the source surface (<1mm) relative to that without
      the backing. This was presumably caused by fluorescent photons from the gold. At
      distances between 1 and 2 cm, the gold backing reduced the dose rate by up to
      12%, which we attribute to a lack of scatter resulting from the attenuation from
      the gold. Dose differences were most pronounced in the radial direction near the
      source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3
      mm off axis at a distance of 1 mm from the source surface. These effects were
      less pronounced in the perpendicular dimension near the source tip, where maximum
      dose decreases of 2% were noted. CONCLUSIONS: I 125 sources embedded directly
      into gold troughs display dose differences of 2 - 90%, relative to doses without
      the gold backing. This is relevant for certain types of plaques used in treatment
      of ocular melanoma. Large dose reductions can be observed and may have
      implications for scleral dose reduction.

PMID- 28519022
TI  - SU-E-J-197: A Novel Optical Interstitial Fiber Spectroscopic System for Real-Time
      Tissue Micro-Vascular Hemodynamics Monitoring.
AB  - PURPOSE: To demonstrate a novel interstitial optical fiber spectroscopic system,
      based on diffuse optical spectroscopies with spectral fitting, for the
      simultaneous monitoring of tumor blood volume and oxygen tension. The technique
      provides real-time, minimally-invasive and quantification of tissue micro
      vascular hemodynamics. METHODS: An optical fiber prototype probe characterizesthe
      optical transport in tissue between two large Numerical Aperture (NA) fibers of
      200MUm core diameter (BFH37-200, ThorLabs) spaced 3-mm apart. Two 21-Ga medical
      needles are used to protect fiber ends and to facilitate tissue penetration with
      minimum local blunt trauma in nude mice with xenografts. A 20W white light source
      (HL-2000-HP, Ocean Optics) is coupled to one fiber with SMA adapter. The other
      fiber is used to collect light, which is coupled into the spectrometer (QE65000
      with Spectrasuite Operating software and OmniDriver, Ocean Optics). The
      wavelength response of the probe depends on the wavelength dependence of the
      light source, and of the light signal collection that includes considerable
      scatter, modeled with Monte-Carlo techniques (S. Jacques 2010 J. of Innov. Opt.
      Health Sci. 2 123-9). Measured spectra of tissue are normalized by a measured
      spectrum of a white standard, yielding the transmission spectrum. A head-and-neck
      xenograft on the flank of a live mouse is used for development. RESULTS: The
      optical fiber probe delivers and collects light at an arbitrary depth in the
      tumor. By spectral fitting of the measured transmission spectrum, an analysis of
      blood volume and oxygen tension is obtained from the fitting parameters in real
      time. CONCLUSIONS: A newly developed optical fiber spectroscopic system with an
      optical fiber probe takes spectroscopic techniques to a much deeper level in a
      tumor, which has potential applications for real-time monitoring hypoxic cell
      population dynamics for an eventual adaptive therapy metric of particular use in
      hypofractionated radiotherapy.

PMID- 28519023
TI  - SU-E-T-23: TomoTherapy Patient QA Using Exit Detector Measurement of Pre
      Treatment In-Air Delivery.
AB  - PURPOSE: Currently, the recommended TomoTherapy patient specific QA involves
      setting up a DQA procedure and delivering it to a phantom with an ion chamber and
      film measurement. The process is time-consuming and the DQA result is susceptible
      to errors in phantom setup. Our study explores the feasibility of using
      TomoTherapy's intrinsic exit detectors to perform patient specific QA by
      measuring the fluence received by the detectors during pre-treatment in-air
      delivery for our STAT-RAD workflow. METHODS: A TomoTherapy patient plan is
      converted into a calibration procedure in which the couch remains out of the
      gantry. The signal measured by the exit detector is exported through manufactory
      provided software. In-house developed software is used to reconstruct exit
      detector signal from the dicom-exported delivery plan. The software relies on
      individual leaf profiles as well as tongue-and-groove profiles of each adjacent
      leaf-pair extracted from an in-house developed calibration procedure. The
      difference between the reconstructed and measured detector signal can be analyzed
      by a simple algorithm which has been developed to estimate the dose difference of
      any given point inside a patient or phantom. Several patient plans have been
      tested with this in-air delivery QA method. In some of the tested plans, errors
      have been introduced to assure the estimated point dose error agrees with the ion
      chamber measurement in a phantom. RESULTS: The in-house exit detector
      reconstruction software has been validated to be able to reconstruct the exit
      detector signal with errors <1%. The software estimated point dose agrees within
      3% to the ion chamber measurement. CONCLUSIONS: Our study shows that it is
      feasible and efficient to perform patient specific QA using the exit detector
      signal recorded during the in-air pretreatment delivery. This approach is easy to
      perform and it is faster than conventional QA approach.

PMID- 28519024
TI  - SU-E-J-209: A Simple Method to Minimize Uncertainty in ITV Delineation: Phantom
      Verification.
AB  - PURPOSE: Irregular breathing causes variation in delineation of internal target
      volume (ITV), which is typically generated in the maximum intensity projection
      (MIP) images [1]. Previous studies have shown that MIP-based ITV can
      underestimate true tumor range [2]. This study examines a simple method to reduce
      such errors by combining the GTV of 3D-CT with the ITV of MIP. METHODS: The
      Computerized Imaging Reference Systems (CIRS) Dynamic Thorax Phantom Model 008A
      (CIRS, Norfolk, VA) with CIRS motion control software was used to model 4
      irregular patient respiratory profiles and one regular respiratory profile (sine
      wave). A 3 cm tumor insert was used as target. For each breathing profile, a 3D
      CT and 3 repeated 4D-CT scans with random intervals within the breathing profile
      were performed on a 4-slice clinical scanner (Lightspeed, GE, WI). The RPM system
      (Varian, Palo Alto, CA) was used to track the respiratory profiles. GTV was
      contoured on 3D-CT, and ITV was contoured on each MIP (ITVMIP) using a consistent
      lung window by the same person. The new method of creating ITV was to combine the
      GTV and ITVMIP, namely ITVCOMB. To evaluate which ITV is more accurate, ITVCOMB
      and ITVMIP were compared to a 'ground truth' ITV (ITVGT) which was generated by
      combining the three ITVMIPs. RESULTS: For the regular profile, both ITVMIP (27.25
      cm3 ) and ITVCOMB (28.12 cm3 ) were comparable to ITVGT (27.25 cm3 ). For
      irregular profiles, the mean absolute difference between ITVCOMB and ITVGT
      (6.3%+/-4.9) was significantly (p-value=0.0078) smaller than that between ITVMIP
      and ITVGT (18.1%+/-12.3). CONCLUSIONS: The results suggest that combining GTV of
      the 3D-CT with the ITV of the MIP is more accurate than the ITV of the MIP alone,
      and thus would be a simple method to reduce breathing irregularity induced errors
      in ITV delineation for treatment planning of lung cancer.

PMID- 28519025
TI  - SU-E-J-199: A Novel Method to Evaluate Local Control and Recurrence Using 18F-FDG
      PET After Lung SBRT.
AB  - PURPOSE: The goal of this study is to evaluate the predictability of a novel
      method using a self background-corrected maximum Standard Uptake Value (cSUVmax)
      from 18F-FDG Positron Emission Tomography (PET) of the patients following lung
      cancer stereotactic body radiosurgery (SBRT). METHODS: 20 qualified patients
      treated out of 38 patients treated with SBRT for a single lung malignant lesion
      between May 2009 and December 2009 were enrolled in the cohort study. All had pre
      and at least one post-treatment PET images available at the time of study. The
      mean normal tissue SUV from the descending aorta was sampled as baseline to
      divide SUVmax of tumor site. The resultant cSUVmax was used for assess the local
      control or possible recurrence. The Result was then compared with that using
      SUVmax alone method. RESULTS: The average follow-up length was 48.9 weeks ranging
      from 18.6 to 115.0 weeks. The mean SUV of aorta was measured as 1.821+/-0.364,
      ranging from 1.173 to 2.576. From the pre-treatment PET, 70% and 65% was
      indicated positive correspondingly when using SUVmax with 2.50 and cSUVmax with
      1.52 thresholds. When PET was taken < 29 weeks post-SBRT, 75% and 67%
      respectively showed higher values in the locally controlled group. For PET = 29
      weeks after SBRT, with cSUVmax both locally controlled and recurrent groups are
      accurately identified, while SUVmax shows 5% false positive and one possible
      false negative. CONCLUSIONS: The SUVmax in lung tumor site corrected by the mean
      SUV of descending aorta or cSUVmax provided a more reliable parameter than using
      SUVmax alone in predicting the local control and recurrence for follow-up PET of
      patients after lung SBRT. The method used in this study objectively displayed a
      strong correlation between low cSUVmax and local control following lung SBRT in
      this investigation, otherwise a local recurrence is suggested.

PMID- 28519026
TI  - SU-E-T-25: Real Time Simulator for Designing Electron Dual Scattering Foil
      Systems.
AB  - PURPOSE: To create a user friendly, accurate, real time computer simulator to
      facilitate the design of dual foil scattering systems for electron beams on
      radiotherapy accelerators. The simulator should allow for a relatively quick,
      initial design that can be refined and verified with subsequent Monte Carlo (MC)
      calculations and measurements. METHODS: The simulator consists of an analytical
      algorithm for calculating electron fluence and a graphical user interface (GUI)
      C++ program. The algorithm predicts electron fluence using Fermi-Eyges multiple
      Coulomb scattering theory with a refined Moliere formalism for scattering powers.
      The simulator also estimates central-axis x-ray dose contamination from the dual
      foil system. Once the geometry of the beamline is specified, the simulator allows
      the user to continuously vary primary scattering foil material and thickness,
      secondary scattering foil material and Gaussian shape (thickness and sigma), and
      beam energy. The beam profile and x-ray contamination are displayed in real time.
      RESULTS: The simulator was tuned by comparison of off-axis electron fluence
      profiles with those calculated using EGSnrc MC. Over the energy range 7-20 MeV
      and using present foils on the Elekta radiotherapy accelerator, the simulator
      profiles agreed to within 2% of MC profiles from within 20 cm of the central
      axis. The x-ray contamination predictions matched measured data to within 0.6%.
      The calculation time was approximately 100 ms using a single processor, which
      allows for real-time variation of foil parameters using sliding bars.
      CONCLUSIONS: A real time dual scattering foil system simulator has been
      developed. The tool has been useful in a project to redesign an electron dual
      scattering foil system for one of our radiotherapy accelerators. The simulator
      has also been useful as an instructional tool for our medical physics graduate
      students.

PMID- 28519027
TI  - SU-E-J-211: Development of Respiratory Training System Using Individual
      Characteristic Guiding Waveform.
AB  - PURPOSE: The purpose of this study is to develop the respiratory training system
      using individual characteristic guiding waveform to reduce the impact of
      respiratory motion that causes artifact in radiation therapy. METHODS:
      Respiratory training system was developed by LabView (National Instruments,
      version 8.6). The real-time respiratory signals were acquired using in-house
      developed belt type sensor and more user-comfortable HMD was used for visual
      guiding (Vuzix, Wrap 920). The respiratory training program consists of three
      main components. It is (1) respiratory signal reading and peak detection program
      (2) individual characteristic guiding waveform generation program (3) respiratory
      signals acquisition and visual guiding program. In order to evaluate the
      feasibility of in-house developed respiratory training system, 5 volunteers were
      included and their respiratory signals were acquired using the in-house developed
      belt-type sensor. Respiratory training system needs 10 free breathing cycles of
      each volunteer to make individual characteristic guiding waveform based on
      Fourier series and it guides patient's next breathing. For each volunteer, free
      breathing and guided breathing which uses individual characteristic guiding
      waveform were performed to acquire the respiratory cycles for 3 min. The root
      mean square error (RMSE) was computed to analyze improvement of respiratory
      regularity in period and displacement. RESULTS: It was found that respiratory
      regularity was improved by using respiratory training system. RMSE of guided
      breathing decreased up to 40% in displacement and 76% in period compared with
      free breathing. The average of RMSE was decreases from 0.012V to 0.008V in
      displacement and from 0.432 sec to 0.192 sec in period. CONCLUSIONS: In
      conclusion, since the guiding waveform was easy to follow for the volunteers, The
      respiratory regularity was significantly improved by using in-house developed
      respiratory training system. So it would be helpful to improve accuracy and
      efficiency during 4D-RT, 4D-CT.

PMID- 28519028
TI  - SU-E-J-181: Explore the Value of 18F-FDG, PET and CT Scan for the Clinical Stage
      of Esophageal Carcinoma.
AB  - PURPOSE: To evaluate the sensitivity, specificity and accuracy of 18F-FDG, PET
      and CT were used for T and N stage for esophageal carcinoma, and explore the SUV
      value evaluating prognosis of esophageal carcinoma. METHODS: PET and CT scan as
      well as T and N stage were carried out for 29 cases of preoperative esophageal
      carcinoma patients, those results were analyzed and compared with postoperative
      pathological TNM stage. RESULTS: CT scan diagnosis the T stage was obviously
      higher than PET in term of determining T staging, while PET scan diagnosis the N
      stage was higher than CT, but there was no significantly difference. It was clear
      that only the Kappa value of preoperative PET scan in T stage was poor (Kappa
      value, 0.4), the Kappa values for PET scan in N stage, as well as preoperative CT
      scan in T and N stage were good (Kappa value.0.4). The SUV values were increasing
      with the lesion volume and length of PETsuv2.5 becoming bigger. The survival was
      better when patients with SUV value, 9.0 than those with SUV value=9.0.
      CONCLUSIONS: CT was better than PET in term of determining clinical T stage of
      esophageal carcinoma, while PET diagnosis the N stage was good the same as CT.
      SUV 9.0 may be regarded as a practical indexes to determine prognosis in
      esophageal carcinoma.

PMID- 28519029
TI  - SU-E-T-08: Simple Governing Equations for Tumor Growth.
AB  - PURPOSE: To derive a set of simple differential equations, which can represent
      temporal growth of typical tumors, by taking into account the effects of the
      tumor microenvironment on cell proliferation. METHODS: Cause-effect relationships
      between cell proliferation and nutrients contained in blood stream, which
      included oxygen and glucose, were modeled. By formulating a set of rate equations
      and simplifying those, we finally obtained two differential equations. One
      equation represents the change of the tumor mass and included time-varying growth
      rate, which was a solution of another equation relating the growth rate with the
      blood volume in the tumor. The set of differential equations were numerically
      solved by varying a parameter, kappa, which represented the growth rate of the
      blood volume relative to the tumor mass. RESULTS: Through numerical experiments
      we showed that the tumor volume increased exponentially if the blood volume
      increased at the same rate as the tumor. However, the blood volume did not
      increase rapidly enough as the tumor grew, the tumor showed the saturation in the
      growth when the tumor grew by 1000-fold. Such a retardation of tumor growth was
      experimentally observed and the function representing the growth curve is called
      as Gompertz equation. One of solutions also showed that the tumor stopped growing
      when the blood supply was shut off (or kappa = 0). CONCLUSIONS: A solution of
      simple differential equations derived in this study could reproduce the tumor
      growth which can be represented by the well known Gompertz equation. Using these
      equations we were able to theoretically show that the saturation of tumor growth
      observed often for larger tumors could be explained by a relative lack of blood
      supply which leads to a decrease in the cell proliferation rate. In a future
      study the effects of radiation on the tumor growth will be included in the model.

PMID- 28519030
TI  - SU-E-J-192: Static Breath-Hold MRI Based Measurement of Change in Pulmonary
      Function Following a Course of Radiation Therapy.
AB  - PURPOSE: Radiation Therapy (RT) induced pulmonary function change may depend on
      the location, underlying function of that lung prior to radiations, radiation
      dose/fractionation and other factors. We propose to evaluate the radiation
      induced pulmonary function change using static breath-hold MRI scans with
      vascular information and 3D deformable image registration which can provide
      pulmonary function relative to RT dose on a regional basis. METHODS: A MRI scan
      pair near the end of inhale and near the end of exhale with breath hold were
      acquired for one lung cancer patient before RT and 6 months after RT. The patient
      was treated with SBRT with 55 Gy to PTVs in the right and the left lung
      respectively. B-spline based vesselness preserving image registration algorithm
      was applied to register the MRI pair for the calculation of local lung expansion
      as a measurement of regional pulmonary function (PF). The PF maps before RT and
      after RT were then mapped to the planning CT using the same algorithm tuned for
      MRI-CT registration. The pulmonary function change was calculated via the PF
      ratio between two MRI pairs. RESULTS: Strong spatial correlation was found
      between the irradiated lung region and the region with greatly decreased PF.
      Based on dose and PFC distribution, no strong determinant factor was found for PF
      lost in the left lung while the right lung shows that all the lung tissue
      receiving dose larger than 28 Gy will have a decreased PF. CONCLUSIONS: We
      demonstrated a method that uses static breath-hold MRI based lung imaging to
      evaluate radiation induced pulmonary function change which can be applied to
      study the dose and the pulmonary function change in a regional basis. This work
      is supported by NIH grant support 1R21CA144063.

PMID- 28519031
TI  - SU-E-T-19: Fitting a Multiple Source Photon Model for Monte Carlo Treatment Plan
      Verification.
AB  - PURPOSE: To assess and reduce the difficulty of fitting a multiple source photon
      model for monte carlo treatment plan verification. METHODS: The EGS4 user code
      MCSIM, from Fox Chase Cancer Center, was chosen for its support of a multiple
      source photon model, of which the point and secondary (extrafocal) photon sources
      were utilized. A described method of fitting the secondary source to in-air
      output factors was implemented. Additionally, a method to fit the point source to
      a single large field dose distribution was explored. The point source fitter
      utilizes a database of pre-simulated mono-energetic fanlines to build
      distributions from arbitrary spectra. Perturbations are made to fanline spectra
      to reduce the errors along them. In this study the energy spectrum for each
      fanline has been limited to the log-normal distribution, which reduces the number
      of parameters for each to two. RESULTS: It was found that one spectral parameter
      could be set to a constant for all fanlines and the other restricted to linearity
      with respect to off-axis position. The model matched the outputs and
      distributions in non-superficial areas to within 2% for 6MV and 15MV Varian iX
      field sizes between 4 and 40 cm. Various types of treatment plans were then
      successfully verified, including 3D, VMAT, IMRT, and an iPlan Monte Carlo
      stereotactic lung to within 3% (tumor dose). CONCLUSION: With such tools it is
      practical for a non-research physicist to fit a two source photon model for the
      purpose of monte carlo treatment plan verification. The only commissioning data
      needed are in-air output factors, a single large field dose distribution, and the
      usual machine parameters provided by LINAC vendors for clinical second check
      programs. Even when only photons are simulated and spectra are greatly simplified
      it is possible to achieve acceptable results for non-superficial tumors.
      Furthermore, this is achieved without proprietary machine specifications.

PMID- 28519032
TI  - SU-E-J-204: The Dosimetric Impact of Daily Setup Error and Inter-Fraction
      Prostate Motion on the Calculated Treatment Plan for Patients Receiving IMRT
      Based Radiation Therapy.
AB  - PURPOSE: Evaluate the dosimetric impact of daily setup error and inter-fraction
      organ motion on the radiation treatment plan. METHODS: Twelve patients undergoing
      definitive IMRT treatments for prostate cancer were evaluated. All patients
      underwent fiducial marker placement prior to treatment planning CT scan, and were
      treated to a dose of 8100cGy given in 45 fractions. We retrospectively created a
      plan for each treatment day that had a shift available. To calculate the dose the
      patient would have received with no setup correction, we mathematically 'negated'
      the shift by moving the isocenter in the opposite direction of the shift. The
      individualized daily plans were combined to generate an overall plan sum. The
      dose distribution from these uncorrected plans was compared to the actual
      treatment plans. RESULTS: A total of 390 shifts were negated and their
      corresponding plans evaluated. The mean isocenter shift based on the location of
      the fiducial markers was 3.3+/-6.5mm to the right, 1.6+/-5.1mm posteriorly, and
      1.0+/-5.0mm along the caudal direction. The mean D95 dose when setup error was
      corrected and uncorrected for the PTV8100 volume was 8089cGy and 7303cGy (p <
      0.001) and for prostate volume was 8228cGy and 7844cGy (p < 0.002). The mean V95
      values when setup error was corrected and uncorrected for the PTV8100 volume was
      99.9% vs. 87.3% (p < 0.0001). At an individual level, the difference in D95 value
      approached 1200cGy for the prostate volume and 2000cGy for the PTV8100 volume.
      There was no statistically significant difference in the D35 parameter for the
      surrounding normal tissue except for the dose received by the right hip and the
      penile bulb. CONCLUSION: This work indicates that significant underdosing,
      approaching 2000cGy for the PTV8100 volume, can occur as a Result of inaccurate
      patient setup, and emphasizes the importance of accurate patient setup and target
      localization.

PMID- 28519033
TI  - SU-E-T-01: Applications of 6MV FFF Photon Beams in Optimizing Radiobiological
      Response for Respiratory-Gated Liver SBRT.
AB  - PURPOSE: To establish a radiobiological basis for gated stereotactic body
      radiotherapy of primary and metastatic liver cancers using volumetric arc
      radiotherapy in a flattening filter free (FFF) mode. METHODS: Human cervical
      carcinoma, SiHa, non-small cell lung carcinoma, H460, and Chinese hamster V79
      cells were irradiated in a water bath with 6MV photons from a Varian TrueBeam
      linear accelerator. To establish dose-response and its sensitivity to dose rate
      following acute irradiation, doses of 2, 4, 6, 8 and 10 Gy were delivered in FFF
      mode at 400 and 1200 MU/min. To investigate whether removal of the flattening
      filter affects cell response, doses of 5 and 10 Gy were delivered to SiHa and
      H460 cells in FFF and filtered modes at 400 MU/min. Finally, to assess the effect
      of protracting dose delivery by gating, a dose of 10 Gy was delivered to SiHa and
      H460 cells acutely and also over 15, 30 and 60 min. RESULTS: Dose-response over
      doses examined was independent of dose rate in FFF mode. Differences in cell
      survival following irradiation in FFF and filtered modes were not significant.
      However a significant increase in survival for both H460 and SiHa cells was
      observed for 15 min split-dose irradiation compared to acute irradiation but
      further increase in irradiation time to 60 min did not affect cell survival.
      CONCLUSIONS: Dose rate and presence of a flattening filter showed no effect on
      cell survival, however, survival was significantly affected when dose delivery
      time was protracted to that typical of conformal field therapy. Volumetric arc
      based gated SBRT may be beneficial for tumor cell kill, though the gating window
      and duty cycle have to be balanced against the effect of dose delivery
      protraction. Research Support (Varian Medical Systems).

PMID- 28519034
TI  - SU-E-J-185: 4DCT Geometrical Eigenmode Model for Inter-Fraction Evaluation of
      Tumor Regression and Breathing Pattern Changes.
AB  - PURPOSE: Evaluate the feasibility of using intra-fractional respiratory dominant
      eigenmodes of lung deformation as a method to track inter-fractional tumor
      regression and other physiological changes. Geometrical evaluation by dominant
      eigenmodes during free-breathing may be implemented as an IGART tool for
      assessing inter-fractional non-respiratory anatomical variation. METHODS: Intra
      fractional deformable image registration (DIR) is performed on 4DCT scans of lung
      cancer patients. Principal component analysis is conducted on a set of 10
      deformation vector fields for each patient both with and without a lung mask.
      Leave-one-out cross-validation (LOOCV) is used to assess intra-fractional
      modeling error among a subset of respiratory phases. The first two dominant
      eigenmodes of PCA are compared across patients in axial, sagittal, and coronal
      slices. RESULTS: Eigenvalues between the first and second dominant respiratory
      modes decay by a factor of ten for all patients. Intra-fractional LOOCV maximum
      error is on the order of 1mm inside the lung and 4-6mm for the whole thorax for
      all patients using the first two dominant eigenmodes. Eigenvalue decay is fastest
      for patients where diaphragm motion is relatively larger in magnitude. The first
      two eigenmodes generally demonstrate a strong but smooth superior-inferior motion
      component with a lesser lateral and anterior-posterior component, while
      subsequent less dominant eigenmodes produce more random directional eigenvector
      fields. CONCLUSION: The two first principal components are consistent amongst
      patients. Inter-fractional eigenmode comparison may provide a means to track
      tumor regression and breathing pattern or physiological changes. We expect that
      patients with more dominant diaphragmatic respiration will allow for more
      delineated eigenmode classification. Clear dominant eigenmode delineation may
      allow subsequent less dominant eigenmodes to be inter-fractionally compared as a
      means to evaluate and compensate for tumor regression.

PMID- 28519035
TI  - SU-E-T-12: Radiation Detector Responses to Applied Homogeneous Transverse and
      Parallel Magnetic Fields.
AB  - PURPOSE: To determine the relative dose response of a diamond detector and a ion
      chamber in a clinical photon beam within uniform magnetic fields, endeavoring to
      evaluate and refine reference dosimetry techniques for use in integrated MR-linac
      systems. METHODS: The Monte Carlo code PENELOPE was used to model the structure
      and materials of the PTW60003 diamond detector and PR06 ion chamber in a 6MV beam
      in the presence of a homogeneous magnetic field. The magnetic field strength was
      varied from 0 to 1.5T, and both the parallel and transverse magnetic field
      orientations with respect to the beam central axis were simulated. The long axes
      of the detectors were oriented both perpendicular and parallel to the radiation
      beam direction for each magnetic field orientation. All simulations determined
      the detectors' signal in air. A small electromagnet was used to experimentally
      determine the detectors' response in transverse magnetic fields up to 0.2T to
      validate the simulations. RESULTS: The simulated response of both detectors
      matched to the experimental data within the estimation error. The relative
      response of PR06 and diamond detector varied up to +/-8.5% (depending on chamber
      orientation) and >9% respectively with increasing transverse magnetic field
      strength. In contrast, both detectors were found to be relatively insensitive to
      the increasing magnetic fields irrespective of the detector orientation in
      parallel magnetic field. A maximum change of 2% in PR06 response was observed at
      1.5T parallel magnetic field and in the parallel orientation of chamber.
      CONCLUSION: This work has significant impact on dosimetry protocols for
      integrated MR-linac systems, where detector response may be altered by the
      presence of a magnetic field. The need for a magnetic field dependent correction
      factor is strongly indicated for the transverse magnetic field cases, while such
      changes in detector response can be largely ignored in parallel magnetic fields <
      1T. CIHR (Canadian Institutes of Health Research) - funding support Faculty of
      Medicine and Dentistry, University of Alberta - funding support.

PMID- 28519036
TI  - SU-E-J-196: In-Vivo Tumor Blood-Oxygen Content Measurement via Interstitial
      Optical Transmission Spectroscopy.
AB  - PURPOSE: To demonstrate the application of in-vivo diffuse optical transmission
      spectroscopy in quantifying oxygen saturation in interstitial tissue, and to use
      this technique to examine reoxygenation dynamics in real-time as tumors responds
      to radiotherapy. METHODS: Two 200 micron core fiber optics were threaded through
      two 21 gauge hypodermic needles: one coupled to an OceanOptics QE65000
      spectrometer, and the other to an Ocean Optics HL-2000-HP 20W light source. These
      needles were fixed approximately 3 mm apart, and inserted into nude mice with
      human head- and-neck tumor xenografts. The oxygen saturation was then measured as
      a function of time after irradiation at intervals of 0.5, 1, 2, 6, 12, and 24, to
      measure the tumors' prompt oxygen saturation response to radiation. RESULTS:
      Blood volume, deoxy and oxy-hemoglobin concentrations were measured through least
      squares fitting of transmission spectra. Furthermore, various configurations of
      interstitial fiber optic probes were explored to optimize signal strength.
      Improvement of the optical coupling to the biological system and a concurrent
      increase in source intensity are the main two focuses for boosting signal
      strength. CONCLUSIONS: This work has the potential to give an understanding of
      the time-scales of hypoxia and reoxygenation in vivo as tumors respond to
      radiation injury. This technique is of particular interest for hypofractionated
      therapies particularly treatments of only two or three treatments, where
      optimizing treatment timing can increase the tumorcidal effect of the remaining
      fractions.

PMID- 28519038
TI  - SU-E-T-05: Comparing DNA Strand Break Yields for Photons under Different
      Irradiation Conditions with Geant4-DNA.
AB  - PURPOSE: To validate and scrutinize published DNA strand break data with Geant4
      DNA and a probabilistic model. To study the impact of source size, electronic
      equilibrium and secondary electron tracking cutoff on direct relative biological
      effectiveness (DRBE). METHODS: Geant4 (v4.9.5) was used to simulate a cylindrical
      region of interest (ROI) with r = 15 nm and length = 1.05 mm, in a slab of liquid
      water of 1.06 g/cm3 density. The ROI was irradiated with mono-energetic photons,
      with a uniformly distributed volumetric isotropic source (0.28, 1.5 keV) or a
      plane beam (0.662, 1.25 MeV), of variable size. Electrons were tracked down to 50
      or 10 eV, with G4-DNA processes and energy transfer greater than 10.79 eV was
      scored. Based on volume ratios, each scored event had a 0.0388 probability of
      happening on either DNA helix (break). Clusters of at least one break on each DNA
      helix within 3.4 nm were found using a DBSCAN algorithm and categorized as double
      strand breaks (DSB). All other events were categorized as single strand breaks
      (SSB). RESULTS: Geant4-DNA is able to reproduce strand break yields previously
      published. Homogeneous irradiation conditions should be present throughout the
      ROI for DRBE comparisons. SSB yields seem slightly dependent on the primary
      photon energy. DRBEs show a significant increasing trend for lower energy
      incident photons. A lower electron cutoff produces higher SSB yields, but
      decreases the SSB/DSB yields ratio. The probabilistic and geometrical DNA models
      can predict equivalent results. CONCLUSIONS: Using Geant4, we were able to
      reproduce previously published results on the direct strand break yields of
      photon and study the importance of irradiation conditions. We also show an
      ascending trend for DRBE with lower incident photon energies. A probabilistic
      model coupled with track structure analysis can be used to simulate strand break
      yields. NSERC, CIHR.

PMID- 28519037
TI  - SU-E-J-208: Dosimetric Assessment of Treatment Using CBCT Images.
AB  - PURPOSE: To evaluate target coverage for five breast patients receiving boost
      treatment to the tumor bed by calculating the daily dose on cone beam computed
      tomography (CBCT) images and utilizing deformable image registration techniques.
      METHODS: The daily dose is calculated on pretreatment CBCT images using the same
      beam configuration as the original volumetric modulated arc therapy (VMAT) plan.
      Calculations were done with two different isocenter positions according to: (1)
      the initial patient setup and (2) the shifts applied for treatment based on CBCT
      verification. The daily doses are deformed and accumulated onto the planning CT
      using commercially available deformable image registration software. The dose
      distribution is compared to the original distribution and tumor and PTV coverage
      is evaluated for both situations (initial and shifted positions). The deformation
      accuracy is evaluated by calculating the change in centroid location and the Dice
      coefficient of deformed contours. RESULTS: The tumor bed is adequately covered
      regardless of the treatment position. The average dose received by 98% (D98) of
      the tumor bed volume differs from the original plan by +1.6% and -0.2% for the
      shifted and initial positions respectively. However, when dose is accumulated in
      the initial setup position PTV coverage is lost; the average D98 for the PTV
      changes by -15.8% and -26.9% for the shifted and initial positions respectively.
      The average change in centroid location is 0.43 mm and 1.53 mm for the left and
      right lung contour respectively. The Dice coefficient for the left and right lung
      is 0.94 and 0.95 respectively. CONCLUSIONS: The margins used to define the PTV
      are sufficient to ensure tumor bed coverage for the given positioning
      variability. We are also confident in the deformation used to deform and
      accumulate dose based on deformed contour comparison. Hardware provided by MIM
      Software Inc.

PMID- 28519039
TI  - SU-E-J-210: Lung Tumor Target Volume Contours on EPID Cine Mode Images.
AB  - PURPOSE: While real time imaging of treatment through an electronic portal
      imaging device (EPID) is a powerful tool to monitor treatment, limited field of
      view and lower contrast from an MV beam can make assessment difficult for
      physicians. This work will develops a method to register and project contour
      outlines for the internal target volume (ITV) and planning target volume (PTV) of
      lung tumor cases onto cine mode EPID images to help physicians in interpretation
      during treatment. METHODS: A sequence of EPID images, acquired during treatment,
      was registered to treatment planning computed tomography (CT) by machine geometry
      and patient setup with cone-beam computed tomography (CBCT). The planning CT was
      converted from Hounsfield scale to electron density by calibration curves of our
      CT simulator and digitally reconstructed radiographs (DRRs) were produced to
      match the EPID geometry, pixel for pixel. ITV and PTV structures as defined on
      the planning CT were then projected onto the DRRs. The DRRs were registered to
      the EPID images using cross correlation of a single template defined within the
      treatment aperture of each image. Once registered, the contours from the DRR were
      transferred to the EPID. RESULTS: We were able to successfully register MV DRRs
      to EPID images and display the projected target volumes. Without introduced
      motion, geometric registration and CBCT guided patient setup up were sufficient
      to register the contours within a single pixel, as normalized cross correlations
      produced no additional shift. We expect the DRR/EPID registration to be an
      important step when looking at cases with substantial tumor movement.
      CONCLUSIONS: The visualization of target volumes provides a tool for physicians
      to interpret EPID images and assess treatment, especially in cases with tumor
      movement. The methods developed will serve as the basis for a clinical tool
      providing real time contours.

PMID- 28519040
TI  - SU-E-T-07: Edema Induced Changes in Tumor Cell Survival Fraction and Tumor
      Control Probability in 131Cs Permanent Prostate Implant Patients.
AB  - PURPOSE: The purpose of this study is to estimate the effect of edema, developed
      during implant procedure, on tumor cell surviving fraction(SF) and tumor control
      probability(TCP) in the patients of prostate cancer who underwent 131 Cs
      permanent seed implants. METHODS: The impact of edema on SF and TCP, was
      calculated using LQ equation extended to account for exponential nature of edema
      decay, dose delivered to dematous prostate and inhomogeneous dose distribution.
      Where (1) S(D)=(1/V)Sigmai=1n [Vpi{1+M0 exp(-lambdae t)}Si (D)] Si (D)=exp[
      alphaRi (0)?0t [exp(- lambdat)/{1+M0 exp(-lambdae t)}tau/3]dt -betaq(t){Ri (0)?0t
      [exp(-lambdat)/{1+M0 exp(-lambdae t)}tau/3]dt }2 ] and (2) TCP=exp[-rhoVpS(D)]
      Following parameters, alpha=0.15Gy-1 , beta=0.05Gy-2 , alpha/beta=3.0Gy,
      Tp=42days, MU=61.6d-1 and rho=1*106 are used to calculate SF and TCP for 31
      patients of 131 Cs permanent seed implants for edema half lives(EHL) ranging from
      4 days to 34 days and for edemas of magnitudes(M0 ) varying from 5% to 60% of the
      actual prostate volume. RESULTS: The dose reductions in 131 Cs implants varied
      from 1.1% (for EHL=4 days and M0 =5%) to 32.3% (for EHL= 34 days and M0 = 60%).
      These are higher than the dose reduction in 125 I implants, which vary from 0.3%
      (for EHL= 4 days and M0 = 5%) to 17.5% (for EHL= 34 days and M0 = 60%). As edema
      half life increased from 4 days to 34 days and edema magnitude increased from 5%
      to 60% the SF increased by 4.57 log, and the TCP decreased by 0.80. CONCLUSIONS:
      Compensation of edema induced increase in the SF and decrease in the TCP in 131
      Cs seed implants should be carefully done by redefining seed positions with the
      guidance of post needle plans. The presented model in this study can be used to
      estimate the SF or the TCP for pre plan or real time permanent prostate implants
      using day 0 post implant CT images.

PMID- 28519041
TI  - SU-E-J-191: A Multivariate Framework for N-Tissue Classification in Treatment
      Assessment of Glioblastomas.
AB  - PURPOSE: Glioblastoma is the most common primary brain tumor in adults and is
      rapidly fatal. Treatment monitoring of these patients has increased awareness
      that many patients have new areas of contrast enhancement without progressive
      clinical signs and symptoms. Although the enhancing areas mimic tumor
      progression, the lesions result from treatment effects and subsequently stabilize
      or improve without further treatment and are not correlated with poorer outcomes.
      This phenomenon has been termed pseudoprogression and is hypothesized to occur
      secondarily to edema and vessel permeability in the tumor area as a result of the
      combined effects of radiation and chemotherapy. Since the new enhancing lesions
      of pseudoprogression are indistinguishable from true disease progression, there
      is a need for a predictive model to distinguish the two phenomena. METHOD: We
      developed a classification algorithm that combines perfusion and diffusion MRI
      imaging to effectively partition the cases as one exhibiting true or pseudo
      progression based on a vector of features containing T1, rCBV and ADC imaging.
      The multi-sequence classification algorithm uses an expectation maximization (EM)
      algorithm that learns from training cases with known clinical outcome to assigns
      each voxel to a type of tissue. RESULTS: A training set of 20 where the clinical
      outcome is known from biopsy or from long-term follow-up was used by EM algorithm
      to model typical imaging values within tissue of pseudo, tumor, edema, necrosis,
      vessels or brain anatomy to construct a database of expected values for each
      tissue type. When presented with a new case, the algorithm automatically
      classifies voxels by their geographical proximities and Mahalanobis distance to
      the pre-sampled values. CONCLUSION: Usage of advanced classification techniques
      allows automated labeling of voxels into normal, pseudoprogression or tumoral
      tissue types. The technique allows for early detection of pseudo progression to
      spare patients from unnecessary surgery or toxic chemotherapy.

PMID- 28519042
TI  - SU-E-T-18: Output Dependence on Dose Rate for Uniform Scanning Proton Beams.
AB  - PURPOSE: Accurate determination of proton output is critical to ensure accurate
      proton dose delivery. It was found that the proton output factor was decreased
      when the dose rate was low. The purpose of the study is to investigate the dose
      rate effects on proton dose output factors. METHODS: We systematically measured
      output (nC/MU) of the proton beam as a function of dose rate for various beam
      conditions. We first measured dose rate effects for proton beams of three range
      and modulation combinations: range 16 cm and modulation 10 cm, range 5 cm and
      modulation 3 cm, and range 30 and modulation 15 cm. We then investigated the dose
      rate effects for two scanning field sizes, the standard 18*18 cm2 and the largest
      available 25*25 cm2. RESULTS: The output factor varied with dose rate, increasing
      more than 6% when the dose rate increased from 0.1 Gy /minutes to about 2.5
      Gy/minute. The output variation on dose rate seems to depend on only the dose
      rate itself. The effect of proton energy and scanning field size on the dose rate
      dependence was minimal. CONCLUSIONS: The proton dose output factor depends on the
      dose rate at our facility, and can be large (>5%). This dependence needs to be
      taken account in output modeling for more accurate proton dose delivery.

PMID- 28519043
TI  - SU-E-J-203: Determination of PTV Margin for Lung Tumor Using In-Treatment 4D
      CBCT.
AB  - PURPOSE: To determine a planning target volume (PTV) margin for lung cancer
      patients using a four-dimensional cone-beam CT (4D CBCT) acquired during
      volumetric modulated arc therapy (VMAT) treatment. METHODS: A VMAT plan for lung
      cancer patients was created by Pinnacle v9.0 (Philips) treatment planning system
      (TPS), where the gross target volume (GTVs) in each breathing phase was
      delineated by using 4D-planning CT scan (TOSHIBA and ANZAI). The VMAT treatment
      was performed with a stereotactic body frame after the registration using Elekta
      X-ray volume imaging (XVI) unit. Simultaneous cone-beam projection images were
      acquired for 3 or 4 fractions of 10 patients. The in-treatment 4D CBCT was
      reconstructed by dividing into four breathing phase bins. A total of 38 in
      treatment 4D-CBCT sets were exported to Pinnacle TPS. The isocenter of in
      treatment 4D CBCT was matched with that of 4D-planning CT. The tumor motion
      during treatment was manually tracked on in-treatment 4D CBCT, and the center-of
      mass (COM) location of the tumor was estimated. Analyzing the tumor regions
      observed by in-treatment 4D CBCT, a PTV margin in our system was derived.
      RESULTS: The average difference in COM location of the tumor was less than 1mm
      for all directions, while the standard deviations (SD's) were about 1.3mm, 1.6mm,
      and 2.1mm for the lateral, the vertical, and the longitudinal directions,
      respectively. The large discrepancy more than 3mm was observed for one patient.
      The required PTV margin was about 3-4mm for the lateral and the vertical
      directions, whereas it was about 5mm for the longitudinal direction. CONCLUSIONS:
      The uncertainties of the tumor motion caused by respiration were observed by in
      treatment 4D CBCT images. It was feasible to determine the PTV margin from 4D
      volume images. K. Nakagawa receives research funding from Elekta.

PMID- 28519044
TI  - SU-E-J-214: Target Intrafraction Motion Dosimetric Impact on 5-Fraction Proton
      Prostate SBRT.
AB  - PURPOSE: To investigate dosimetric impact of prostate intra-fraction motion to
      five fraction hypofractionated proton treatment with uniform scanning (US) and
      double scattering (DS) techniques using real-time prostate tracking data from
      electromagnetic transponder system. METHODS: Prostate intra-fraction motion can
      have spatiotemporal interplay with proton treatment delivery. Five fraction
      (7.25Gy/fraction) prostate proton stereotactic body radiotherapy (SBRT)
      treatments were simulated for total 14 patients using in-house proton treatment
      simulation program. The US treatment was simulated by rigidly moving CTV through
      a series of temporal-spatial dose matrices indexed by energy layers, according to
      prostate motion traces. The CTV temporal doses of the whole treatment fraction
      were obtained and summed as final prostate CTV dose. The DS treatment was
      simulated by moving CTV through the energy layer summed dose matrix. For all
      patients, the fraction doses and the total dose to the CTV were presented for
      both DS and US treatments. RESULTS: The CTV dose of different fractions indicated
      that its dose degradation depends on magnitude and direction of prostate intra
      fraction motion and is patient specific. For one of the prostate motion traces
      investigated, only 70% of CTV received 100% prescribed dose for a simulated US
      treatment and 79% CTV had 100% dose for a DS treatment. Furthermore, DVH and
      isodose graphs of both treatments revealed that intra-fraction motion caused
      significant CTV cold and hot spots in US treatment whereas only cause CTV
      underdose in DS treatment. CONCLUSIONS: Intra-fraction prostate motion causes
      dose uncertainty to CTV. In the 5 fraction prostate SBRT, prostate intra-fraction
      motion causes significant target dose degradation. In US treatment,
      spatiotemporal interplay between energy layers delivery and prostate motion leads
      to hot and cold spots in CTV for some patients with severe prostate intra
      fraction motion. Further investigation of intra-fraction motion management and
      its impact on CTV dose is necessary.

PMID- 28519045
TI  - SU-E-J-184: Liver Dose Calculation for 90Y Radioembolization with PET/CT.
AB  - PURPOSE: 90Y radioembolization is a promising treatment for unresectable
      hepatocellular carcinoma. A dose of 120 Gy is typically prescribed to a segment
      or lobe of the liver, but dose of 90Y in the liver tumor is highly heterogeneous.
      Recently developed 90Y PET/CT enables the visualization of the injected 90Y
      distribution with high resolution. The purpose of this study is to develop an
      integrated system to quantify 3D dose distribution using PET/CT images. METHODS:
      According to our institution's protocol, 90Y PET/CT scan is acquired for each
      patient two hours after radioembolization. Based on the 90Y activity distribution
      from PET scans, we used a convolution method to calculate radiation dose with a
      published dose kernel for 90Y. The gross tumor volume (GTV) was retrospectively
      contoured by a clinician using contrast-enhanced diagnostic CTs. Because of
      breathing motion and different patient positions between the diagnostic CT and
      PET/CT, we manually registered these two CT scans by aligning 200 Gy dose line
      with the center of the intended treatment GTV. RESULTS: The system was integrated
      with a commercial RT PACS/Review station (MIMVista) through DICOM. The dose
      obtained was of the resolution of PET scans (2-4 mm). This distribution enables
      physicians to quantify treatment volume and dose relationships either through 3D
      dose distributions or dose volume histograms. For the five patients tested for
      our program, liver mean doses agree with clinical results within 5%. We were able
      to quantify radiation doses to 95% of GTV, and radiation dose received by the
      CTVs extended 5 mm from the GTV. CONCLUSIONS: The system is easy to use for
      radiation oncologists. With this system, clinicians can quantitatively evaluate
      delivered dose of 90Y treatment in high resolution. No conflict of interest for
      this work.

PMID- 28519046
TI  - SU-E-T-11: LINAC Dose Profiling Using Cherenkov Emission Imaging.
AB  - PURPOSE: To demonstrate the potential for fast 3D dose profile imaging of a LINAC
      beam using images of the induced Cherenkov radiation in a water tank. A
      specialized time-gated imaging system was developed as a prototype to quantify
      and compare with Monte Carlo, to illustrate the concept. METHODS: Images were
      acquired from a water tank during irradiation from a 6 MV Varian-2100C linear
      accelerator beam using a time-gated CCD-based imaging system. The camera was
      placed normal to the tank wall to minimize parallax reflections, and resultant
      images were produced by evaluating the median of each pixel in a stack of 2000
      images taken at a rate of 60 Hz with an exposure time of 10 ms. Experimental data
      was compared to images obtained from GEANT4 simulations of the optical setup.
      RESULTS: Examination of the scored quantities for dose and generated Cherenkov
      photons indicates that there is a strong similarity, which can be explained by
      considering the electron energy losses per unit path length. However, due to the
      complex convolution of the Cherenkov emission directionality and camera lens
      angular field of view, this relationship is distorted. These errors can be
      calibrated using the GEANT4 simulations to more accurately reflect the intrinsic
      dose in the water volume. CONCLUSIONS: This work demonstrates dose profiling
      using the induced Cherenkov radiation signal for the first time. These
      preliminary results serve as a proof of concept of imaging at one azimuthal
      angle. Analogous to SPECT, the technique could easily be translated to multiple
      angles yielding full dose reconstructions following filtered back projection.
      Further refinement of this technology could be the first step in a paradigm shift
      towards an alternative method for fast radiation field analysis. Advantages would
      include increased speed, as well as the ability to profile dynamic beam shapes
      within transparent solid anthropomorphic phantoms. This work has been financially
      supported by NIH grant R01CA109558.

PMID- 28519047
TI  - SU-E-J-195: Dosimetric Consequences of Metal Prosthesis in Prostate 3D CRT by
      Using Monte Carlo Dose Calculation Method.
AB  - PURPOSE: To investigate dosimetric consequences of patient metal prosthesis in
      prostate radiotherapy, considering the body heterogeneity, metal artifacts,
      prostate daily displacements and target delineation. METHODS: Three prostate
      patients with metal prosthesis were simulated with CT images and 3D ultrasound
      images. Conformal RT treatment plans were generated based on target volumes
      delineated on CT images without artifact correction (PTVa). The patients'
      treatments were aided with an ultrasound (US) localization system for daily PTV
      setup correction. We retrospectively reevaluated the delineation of PTVs by 1)
      using simulation CT images artifact-corrected by using an algorithm developed by
      M. Bazalova et al (2007) (PTVc) and 2) using the 3D ultrasound simulation images
      as guide (PTVus). Daily setup corrections to the PTVs were incorporated to
      calculate composite delivered dose by using XVMC simulation on the patient
      phantom derived from the artifact-corrected CT images. DVHs and dose
      distributions for different PTVs were then compared with the reference treatment
      plans (XVMC-calculated on the artifact-degraded CT images). RESULTS: The PTVa
      volume was the largest, about 1.3% larger than artifact-corrected PTVc and 5.2%
      larger than PTVus. Adapting artifact-corrected CT images can improve the DVH
      curves of PTVc and increase the D95% and V95% for PTVc by more than 5% while D50%
      and V50% for rectum and bladder are raised by up to 41.6%. DVH analysis on PTVa
      and PTVus shows a small difference in the changes of their DVH indices, less than
      4% for the studied cases. CONCLUSIONS: The strike artifacts from metal prosthesis
      will increase the volume of PTVa, and affect the patient dose calculation.
      Original patient plan did not accurately predict the dose degradation. Artifact
      correction may be necessary for some cases having severe metal artifacts. Using
      US images to help delineating PTV makes a negligible clinical significance.

PMID- 28519048
TI  - SU-E-T-22: Is the Residual Range a Universal Quantity to Specify the Quality of
      Modulated Proton Beams?
AB  - PURPOSE: To investigate the validity of using the residual range as a universal
      quantity to specify the quality of modulated proton beams. METHODS: We used TOPAS
      (Tool for Particle Simulation), an application of the Geant4 toolkit, to simulate
      absorbed dose and stopping-power distributions from a commercial passive
      scattering nozzle. We used the standard physics lists from Geant4 in the
      simulations. All particles were included, as well as physics models for nuclear
      interactions. No variance reduction techniques were used. Dose and averaged
      stopping-power as functions of depth were scored in a water box with 320 scoring
      volumes of 15 * 15 * 0.1 cm3 . Stopping-power spectra were scored in a15 * 15 *
      0.1 cm3 volume located in the middle of SOBPs. All particles were considered in
      the dose scoring. Only protons (primary and secondary) were considered in the
      scoring of stopping-power. RESULTS: For the same residual range, differences in
      averaged stopping-power values of up to 13% were observed for a 200 MeV beam with
      modulations of 4 cm and 8 cm, respectively. Simulations of four modulated proton
      energies with the same SOBP of 8 cm showed differences of up to 13% in the
      averaged stopping-power values even in the SOBP region. We also simulated
      stopping power spectra in the middle of 8 cm SOBPs for four modulated proton
      energies. The averaged stopping-power values calculated from the spectra were
      within 3%, however, their distributions were very different with full width at
      half-maximum 150% larger for the 250 MeV beam compared to that of the 140 MeV
      beam. CONCLUSION: Large differences in the averaged stopping-power values and
      stopping-power spectra were observed for the same residual range. Determining
      whether these differences have a significant effect on the response of radiation
      detectors exposed to proton beams requires further investigation. Natural
      Sciences and Engineering Research Council of Canada and Ontario Graduate
      Scholarship Program, Ontario Ministry of Training, Colleges and Universities.

PMID- 28519049
TI  - SU-E-J-207: Compensation of Target Distortion of Pancreatic Tumor in Free
      Breathing CT Using 4D Contour Propagation.
AB  - PURPOSE: Due to lack of soft-tissue contrast, target distortion for the upper
      abdomen targets such as pancreatic tumors is complicated and requiring sufficient
      remedy. By applying automatic contour propagation, the authors use the
      information obtained from 4D CT to test if the deformable image registration
      compensates the respiration-induced distortion of pancreatic tumor in free
      breathing (FB) CT images. METHODS: Ten patients with unresected pancreatic cancer
      treated with either preoperative or definitive chemoradiation were studied.
      Pancreas GTVs were delineated on the FB CT. Using deformable image registration,
      the FB GTV contours were propagated to each phase of the 4D CT images taken right
      after the FB CT, and were compared with the FB GTV to see difference in tumor
      volume and tumor size along individual dimensions. A one-dimensional tumor motion
      in proportion to cos4(omegat) was simulated to calculate the probability
      distribution function for different magnitude of distortions during FB CT scans,
      and a binary classification test was conducted to analyze the observed results.
      RESULTS: The probability distribution function predicted that four out of the ten
      cases would have substantial target distortion given the variation in target
      motion amplitudes. Three of these four cases show substantial difference in the
      superior-inferior size of FB GTV compared to the average 4D GTV, taking into
      account the uncertainties caused by motions perpendicular to the scanning axis
      and resolution of the CT scanner. The binary classification test yielded a
      precision of 75% and an accuracy of 90%. CONCLUSIONS: Pancreatic GTV distorted
      due to respiration-induced tumor motion is effectively compensated by contour
      propagation from free-breathing CT to 4D CT using DIR. Union of GTVs of all
      breathing phases or IGTV can be genreated from 4D set of GTVs propagated from
      that of free breathing. This study is partially supported by NIH grant
      1R01CA133539-01A2. I do not have conflict of interest.

PMID- 28519050
TI  - SU-E-T-04: Repair Kinetics of Sublethal Damage in Rat Cervical Spinal Cord -
      Application of the GLQ Model Incorporating Reciprocal Time Pattern.
AB  - PURPOSE: The repair rate conventionally assumed to be constant during the entire
      radiation course. However, increasing evidences from animal studies show that the
      repair process may slow down with time and the experimental data does not fit an
      exponential pattern. To address this enigma, we presented a generalized linear
      quadratic (gLQ) model incorporating reciprocal time repair pattern of sublethal
      damage and fit the model to published experimental data. METHODS: In the gLQ
      model, the parameter G in the surviving fraction represents the repair process of
      sublethal damage with Tr as the repair half-time. When a reciprocal time pattern
      of repair process was adopted, a generalized form of G was derived analytically
      for arbitrary radiation schemes (I(t) = Ii, ti-1 < t < ti, where i=1 to N, Ii is
      the dose rate of the ith segment to the voxel in question, and N is the total
      number of segments for the entire treatment course). The published animal data
      was used to test the reciprocal formulas. RESULTS: The gLQ model incorporating a
      reciprocal time pattern to describe the repair process was used to fit the
      experimental data. The reciprocal model showed better fit to the animal data than
      the exponential model, particularly for the ED50 data, resulting in the following
      parameters: the reduced chi-square of 1.52, alpha/beta=0.9 Gy, Tr =1.0 h for the
      reciprocal model and reduced chi-square of 3.39, alpha/beta=1.6 Gy, Tr=3.5 h for
      the exponential model. CONCLUSIONS: The modeling results suggest that the gLQ
      model incorporating the reciprocal time pattern of sublethal damage repair
      facilitates the interpretation of complex experimental designs, especially for
      irregular dose delivery schedules. These formulas can be used to analyze
      experimental and clinical data, where a slowing-down of the repair process occurs
      during the radiation therapy course.

PMID- 28519051
TI  - SU-E-J-188: Lung CT Density Changes during the Conformal Radiotherapy: A
      Prediction for Lung Radiation Pneumonitis.
AB  - PURPOSE: Radiologic lung density changes are observed durng radiotherapy for lung
      cancer. We studied the relationship between dose and computed tomography (CT)
      density changes during the treatment, a prediction for lung radiation
      pneumonitis. METHODS: 30 Stage a...c lung cancer patients with CRT were thirty
      fractions of 2.0 Gy, prescribed at the 90% isodose. Follow-up CT scans performed
      at less than 3 weeks (n=15) and between 3 and 6 weeks (n=15) after CRT
      radiotherapy were reviewed. New CT scans were coregistered with baseline scans
      using CT-CT normalized mutual information registration algorithm. Voxel
      Hounsfield unit histograms were created for doses between 0.5 and 50 Gy. Linear
      mixed effects models were used to assess the effects of CRT dose on CT density,
      and the influence of possible confounders was tested. RESULTS: Increased mean CT
      density was associated with higher dose, increasing planning target volume size,
      and increasing time after CRT (all p <0.05). Density increases were apparent in
      areas receiving 20 Gy, but seemed to plateau above 40 Gy. In regions receiving
      >30 Gy, the reduction in air-filled fraction of lung during treatment was up to
      20%. No increase in CT density was observed in the contralateral lung receiving
      less than 5 Gy. CONCLUSIONS: A dose-response relationship seems to exist for
      quantitative CT density changes during CRT radiotherapy. The density between old
      and new CT during the treatment could be a prediction for lung injury.

PMID- 28519052
TI  - SU-E-T-15: Small and Nonstandard Photon Field Dosimetry Characterization Using
      Monte Carlo Methods.
AB  - PURPOSE: To quantify uncertainty reduction in small photon field dosimetry
      through characterization of ionization chambers and calibration conditions using
      detailed Monte Carlo methods benchmarked against NIST-traceable measurements.
      METHODS: Phase space profiles were obtained using detailed EGSnrc Monte Carlo
      models for a Varian 6 MV photon linear accelerator, and a NIST-traceable cobalt
      60 teletherapy unit. The responses of a farmer-type ionization chamber, two micro
      ionization chambers, and one scanning-type ionization chamber were simulated in
      multiple calibration conditions. Calibration conditions included static field
      sizes ranging from (10*10) cm squared to (0.5*0.5) cm squared for the 6 MV and
      cobalt-60 beam qualities and an additional dynamic IMRT plan for the 6 MV beam
      quality. Calibration conditions also consisted of ionization chambers placed in a
      standard water phantom and in a specially designed acrylic phantom. Tolerance
      limits on the calibration conditions were investigated. All models were
      benchmarked against measured beam quality data, including ionization chamber beam
      quality correction factors for the standard absorbed dose to water cobalt-60
      calibration coefficient. RESULTS: The majority of the simulated small field
      response values fell within the uncertainty of the measured values. A database
      was created for several proposed small field calibration conditions to provide
      comparisons with the Co-60 standard reference conditions. The database includes
      the small field calibration conditions' beam quality correction factors,
      tolerances, and dose calibration uncertainties. CONCLUSIONS: The characterization
      of multiple calibration conditions provided an improved understanding of how the
      cobalt-60 ionization chamber absorbed dose to water calibration coefficient from
      an ADCL can optimally be applied to small and nonstandard field calibrations to
      reduce the associated dose uncertainty. The developed methodology will contribute
      to future research of other small field radiotherapy modalities. The resulting
      database provides support for future recommendations on the implementation of
      small and non-standard field calibration protocols.

PMID- 28519053
TI  - SU-E-T-06: A Mathematical Explanation to Tumor's Response to Perfusion and
      Hypoxic Fraction after Radiation.
AB  - PURPOSE: To develop a dynamic model that explains oxygen dynamics between the
      microvascular perfusion and the hypoxic cell population inside a tumor. METHODS:
      Bussink et al (Radiat Res 153(4), p.398 (2000)) observed fast oxygen dynamics,
      faster than cell-death. Based on a simplified three-compartment-model: the
      microvasculature, well-oxygenated, and hypoxic tumor cell populations. We applied
      a first-order differential model for the tumor's transient response as a function
      of oxygen content within the blood vessels. The sink terms in our model for each
      compartment are fast changing parameters because radiation rapidly changes the
      oxygen consumption of the tumor cell in a time scale which is much faster than
      the population changes of the tumor. Transportation balance condition is also
      applied for each compartment. RESULTS: Our simulation results can explain the
      experimental data in Bussink et al's (Radiat Res 153(4), p.398 (2000)) paper. We
      provide an explanation for the relative complex behavior of the microvascular
      perfusion after radiation that emphasizes the role of dynamic metabolic changes
      in addition to population changes. CONCLUSIONS: A newly developed dynamic model
      leads our understanding to the interrelationship between microvascular oxygen
      content within the blood vessels and the hypoxia state of the tumor to a deeper
      level, which has the potential to provide the theoretical foundation for the
      patient' specific adaptive radiotherapy.

PMID- 28519054
TI  - SU-E-J-190: A Possible Non-Typical Measurement in Dynamic Contrast MRI for Brain
      Tumor Therapy Response Evaluation.
AB  - PURPOSE: Dynamic susceptibility contrast (DSC) MRI technique can be used for
      brain tumor therapy response evaluation. However, the typical modeling (Eqs.1) is
      sometimes problematic in the vicinity of tumor due possibly to the disrupted
      microvascular environment associated with the disease. The example is well
      illustrated in Fig.1B, where some MRI time series curves (TSC) keep increasing
      beyond the baseline value after some time points, which is theoretically
      prohibited in the typical modeling. This behavior is not related to other
      systemic error such as motion or system instability, which can be verified by the
      steady TSC from a CSF region (Fig.1C).To improve the utility of DSC-MRI even in
      the problematic, but highly interested, regions of the brain, the non-complying
      TSC was assumed legitimate and its increase rate, linked to the degree of
      contrast's leakage, was analyzed. METHODS: DSC-MRI (with manually injected
      multihance, 0.2 ml/kg) was applied for high grade brain tumor before and after
      radiation therapy. The scan technique was based on T2*-weighted PRESTO
      implemented on a Philips 1.5T scanner. The analysis of TSC was performed using an
      in-house software developed in MATLAB. RESULTS: The TSCs from several regions of
      interest (ROI) were obtained (Fig.1). Before radiation therapy, those from ROIs A
      and C increase beyond the baseline after about 60 frame that coincides with the
      passage of contrast in other complying TSC. The slope of increasing TSC was
      determined as shown in Figs. 1B and 1D. After therapy (Fig 1D), the compliance of
      TSC in ROI C to the typical modeling was quite improved and the degree of leakage
      shown as slope, as well as the area of leakage (Fig 2), decreased after the
      therapy, suggesting the therapy possibly repaired the leakage. CONCLUSION: A non
      typical measurement was introduced to improve DSC-MRI's utility in the brain
      tumor therapy monitoring. American Cancer Society Institutional Research
      Grant/Upstate Cancer Research Institute.

PMID- 28519055
TI  - SU-E-T-17: Comparison of MCNP5 Calculations in the Buildup Region with Plane
      Parallel Ionization Chamber Measurements for 6 and 18 MV Photon Beams.
AB  - PURPOSE: Cylindrical ion chambers are known to overestimate the dose in the
      buildup region, where gradients are high. The potential for MCNP5 to produce
      accurate calculations in this region, even when benchmarked with a large volume
      chamber, was tested. METHODS: MCNP5 was used to model 6 and 18 MV photon beams
      for a Varian accelerator using vendor geometry with the collimator corrections of
      Chibani and Ma. Modeling was benchmarked by adjusting electron beam energy and
      diameter to match calculations with ionization chamber (with 0.125 cm3 sensitive
      volume) measurements of percent depth doses (PDDs) beyond dmax and cross dose
      profiles for 5*5, 10*10 and 30*30 cm2 field sizes. For comparison in the buildup
      region, the MCNP5 voxel was reduced to 1 mm, with extrapolation to find surface
      dose. In this region a plane parallel chamber (with 0.055 cm3 sensitive volume)
      was used to measure PDDs at 0, 2 and 4 mm depths for the three field sizes, using
      the Khan over-response correction. RESULTS: Calculations and cylindrical chamber
      measurements for PDDs beyond dmax agree within 2% for all field sizes and
      energies. Dose profiles at dmax (1.5 cm and 3.3 cm for 6 and 18 MV) and at 10 cm
      agree within 2% in the flat region and within 10% in the penumbra. In the buildup
      region, the MCNP5 calculations agree with plane parallel PDD measurements within
      3% at 2 and 4 mm depths. The extrapolation of the MCNP5 PDD overestimates the
      surface dose for the 18 MV beam for the 30*30 cm2 field, and is within 4.2% for
      the smaller fields and for all field sizes at 6 MV. Improved extrapolation
      techniques may yield better surface dose agreement. CONCLUSIONS: Accurate dose in
      the buildup region can be calculated by MCNP5.

PMID- 28519056
TI  - SU-E-J-202: Treatment Dose Assessment with the Consideration of Radiation Dose
      Inducible Organ Shrinkage/Deformation.
AB  - PURPOSE: For asymmetric organ shrinkage caused by heterogeneity dose
      distribution, tissue elasticity based deformable organ registration cannot be
      directly applied to the treatment image to construct the treatment dose. A novel
      approach is proposed to include radiation dose inducible organ
      shrinkage/deformation in the consideration of treatment dose assessment. METHODS:
      A model and algorithm were developed to include dose inducible organ shrinkage in
      the deformable image registration. In the model, we assume that the logarithm of
      tissue-element volume shrinkage ratio is proportional to the LQ survival
      function, and the tissue-element displacement field is the gradient of a scalar
      potential function. The derived Poisson equation of the potential was solved
      using a finite element method. Two steps registration was implemented to
      determine the tissue-element volume and displacement. The first is the
      conventional deformable image registration to determine the organ surface. The
      second is to map the element volume/position in the shrinking organ with using
      the dose inducible shrinkage model. Treatment dose was constructed by applying
      both the conventional deformable registration and the shrinkage model on CBCT
      images obtained from h&n treatment. The dose distribution in the patient parotid
      was evaluated. RESULTS: Treatment dose-volume, V30, constructed including the
      dose inducible parotid shrinkage was 11% higher than the one from the
      conventional deformable image registration and dose construction. Tissue elements
      in the high dose region shrink more than those in a low dose region which results
      in extra tissue elements in the organ move into the high dose area during the
      treatment course and an unfavorable dose-volume relationship in the organ.
      CONCLUSIONS: Without including dose inducible organ shrinkage, treatment dose in
      a shrinking organ could be underestimated. On the other hand, including this
      effect in the treatment evaluation and adaptive planning optimization will
      minimize the potential detriment of the effect.

PMID- 28519057
TI  - SU-E-J-213: Comparison of the Effect of Metal Implants in Three Different
      Radiation Therapy Modalities; IMXT, Tomotherapy, and Proton Therapy.
AB  - PURPOSE: To compare and evaluate the dosimetric effect of metal implants in 3
      different radiation therapy modalities, photon IMRT, Tomotherapy, and Proton
      Therapy. METHODS: We have constructed two sets of PMMA phantom with and without
      titanium alloy orthopaedic implants embedded. Combinations of the two phantom
      sets provide a hole in the middle for a dose measurement using ion chambers and
      also a space in which an EBT film can be inserted for a measurement of dose
      distribution in that plane. The phantoms have been CT-scanned separately and will
      be planned in 3 different treatment modalities (IMXT, Tomotherapy, and Proton
      therapy in passive scattering mode). In each plan, we make an assumption that the
      beam path(s) should include the metal implants so that we can compare the
      dosimetric effect in different modalities directly. The plan comparison between
      the three modalities will be made. In addition, point doses and dose
      distributions of the plans will be measured using ion chambers and EBT films and
      compared to the Result of the plan study. RESULTS: The plan outcome of three
      different modalities shows different properties as expected. The uncertainty due
      to the presence of high-density metal is not only coming from the metal artifacts
      in CT numbers but also coming from the distinct physical property of the metal
      especially for the proton therapy. The most suitable treatment modality among the
      three treatment methods in various aspects will be detemined. CONCLUSIONS: The
      comparison Result would provide a guideline for the selection of radiation
      therapy modalities in the presence of metal implants and help to make decisions
      based on quantitative supporting data. In addition, the Result would be a basis
      for the further study to effectively avoid the undesired effects of the metal
      implants in radiation therapy especially for the proton therapy.

PMID- 28519058
TI  - SU-E-J-183: Dose Distribution Generated from 131 I Radionuclide Using SPECT-CT.
AB  - PURPOSE: 131 I radionuclide therapy is widely performed in a thyroid cancer
      treatment, but there has been almost no evaluation of the dose distribution. The
      aim of this work is to develop the calculation system using the data of SPECT-CT
      and to examine the effects of their image resolutions on the dose distribution.
      METHODS: We designed and constructed an acrylic phantom for measurement. A
      radioactive iodine capsule and glass dosimeters can be set in the layer structure
      of the phantom. We put iodine capsules (37MBq, 111MBq, 185MBq) in the middle of
      the phantom and acquired SPECT-CT (Infinia Hawkeye4 (GE)) images. Both the CT
      value data (image resolution: 1.1 mm) and the intensity map data of SPECT (image
      resolution: 4.4 mm) were independently used for the estimation of the cumulative
      dose distribution generated from the radioactive iodine in the phantom. We
      adopted Monte Carlo program PHITS2.0 as the simulation of the dose calculation.
      The absolute dose was measured by glass dosimeters. RESULTS: The measurement
      result by glass dosimeters was very similar to the Monte Carlo simulation result,
      in which the difference was about 0.3 %. We obtained the dose distributions
      reconstructed by the radioactive iodine distribution using CT value data and
      SPECT data, respectively. The iodine distribution from CT could be finer than
      that of SPECT data because of its higher image resolution. As a result, the
      difference was found to be factor two in the middle of the iodine distribution.
      On the other hand, both of the dose distribution was almost same above 2.2 cm
      distance from the center. CONCLUSIONS: We can reconstruct the 131I dose
      distribution using SPECT-CT data. For more accurate calculation of the dose
      distribution, it would be crucial to increase the resolution of SPECT data.

PMID- 28519059
TI  - SU-E-T-10: Monte Carlo Study of the Dose Enhancement Factor (DEF) for Gold Nano
      Particle (GNP) on the Cellular Level.
AB  - PURPOSE: In megavoltage external beam radiotherapy, in vivo cell experiments
      suggest GNP could be used as a radiosensitizer by having radiation dose
      enhancement factor (DEF) significantly larger than 1. However, Monte Carlo (MC)
      simulations published in the literature failed to give prove, in which most of
      them only simulated the interactions between the radiation beams and a single
      GNP. In this study, we built a multi-GNPs model considering possible spatial
      arrangements of GNPs relative to a cell to calculate the DEFs of GNPs. METHODS:
      Geant4 MC code with G4DNA physics model which can trace electrons down to eV
      level was used. Two types of geometry models representing different GNP-cell
      binding were created with each GNP modeled individually: (1) shell model with
      GNPs randomly and sparsely distributed in a shell in water mimicking when the
      GNPs were binding to the cell membrane, and (2) sphere model with GNPs randomly
      and sparsely distributed in a sphere in water mimicking when GNPs were floating
      inside the cytoplasm. Photon and electron spectrum at 5 cm in depth in water from
      a Varian 6MV beam was used as the radiation source. Dose to water inside the
      shell or the sphere representing cytoplasm were scored and compared to situations
      without GNPs to calculate the DEF. We also looked into the variation of DEFs due
      to different GNP sizes and concentrations. RESULTS: A 35 um water cubic were
      successfully built in Geant4 with spatial resolution of 100 nm. Preliminary
      results shown under 200 keV electron irradiation, 100 nm GNPs in the shell model
      shown increased dose to cell at the beam entrance (DEF = 1.08). CONCLUSIONS: The
      computation is undergoing for different GNP sizes and concentrations. Meaningful
      results are expected on the completion of this study.

PMID- 28519060
TI  - SU-E-J-194: The Impact of Different Imaging Measures on Treatment Response
      Assessment of Bone Metastases.
AB  - PURPOSE: Several treatment response metrics, such as RECIST and PERCIST, have
      been established for assessing individual solid tumors. However, metastatic
      prostate cancer poses a unique challenge to these metrics because bone lesions
      are often numerous and non-measureable. This study investigated the impact of
      using different imaging measures for treatment response assessment in patients
      with metastatic prostate cancer. METHODS: Six patients with metastatic prostate
      cancer were treated with molecular targeted therapy and received whole body [18
      F]NaF PET/CT scans pre-, mid-, and post-treatment. Lesions were segmented using a
      threshold of 20% the maximum SUV in bone and then manually adjusted with
      physician guidance. For each patient, SUVmax, SUVmean, SUVpeak, SUVtotal, number
      of lesions, and total volume of bone lesions were determined. For each measure,
      treatment response was calculated as the percent change relative to pre
      treatment. The range of the different responses was calculated for each patient
      at each response time point. The population average of the patient ranges was
      calculated. RESULTS: The patient responses varied greatly for different imaging
      measures. The population-averaged range for all response measures was 50%. In
      general, SUVmax, SUVmean, and SUVpeak responses were negative, indicating good
      response to treatment, but the number of lesions, volume, and SUVtotal responses
      were positive, indicating disease progression. When the measures were separated
      into these two groups, the population-averaged range was only 25% among the
      number of lesions, volume, and SUVtotal responses and 10% among the SUVmax,
      SUVmean, and SUVpeak responses. CONCLUSIONS: Several treatment response metrics,
      such as RECIST and PERCIST, have been established for assessing individual solid
      tumors. However, metastatic prostate cancer poses a unique challenge to these
      metrics because bone lesions are often numerous and non-measureable. This study
      investigated the impact of using different imaging measures for treatment
      response assessment in patients with metastatic prostate cancer.

PMID- 28519062
TI  - SU-E-J-206: Are We Treating the Entire Lung Tumor by Contouring ITV on 4DCT MIP?
AB  - PURPOSE: To describe a case report of lung radiosurgery in which defining a
      target using a maximal intensity projection CT omitted a portion of the target
      due to an overlapping projection of the diaphragm. METHODS: A Lung 4DCT was
      obtained, and all ten breathing phases from 0% to 90% were reconstructed. The
      gating window was set to treat phases 30% to 70%, and the corresponding Maximum
      Intensity Projection (MIP) was generated. An ITV was contoured on the MIP. Tumor
      GTVs were contoured on all phases. Another ITV was generated by using the
      overlapped projection of all GTVs in the gating window when suspicion arose that
      part of the target was omitted. The volumes of the ITVs and GTVs were calculated.
      DVHs were analyzed on the plan generated to cover the MIP ITV. RESULTS: The
      initial ITV based on the MIP omitted 15% of the target Since the ITVs of the
      diaphragm and the tumor overlap in the MIP, and the imaging technique cannot
      differentiate them, contouring tumor only on MIP has risk of missing part of the
      tumor. We have also found that the volumes of all 10 phases fluctuate with a
      standard deviation of 5.6%. This indicates the imperfection of 4DCT generation.
      If the treatment plan was generated based on MIP ITV, DVH shows the lack of
      coverage for the true ITV. CONCLUSIONS: We propose two methods to accurately
      delineate tumor ITV from 4DCT for cases in which the target is located adjacent
      to diaphragm. If it is desired to start with contouring ITV on MIP, thorough QA
      needs to be done by going through all gating phases to adjust the ITV
      accordingly. A more straightforward method is to contour the GTV on all gating
      phases and use the overlapped projections as the ITV.

PMID- 28519061
TI  - SU-E-T-21: Modeling a MLC Scatter Source for In-Air Output Factors.
AB  - PURPOSE: Scattered radiation from multi-leaf collimators (MLCs) is no longer
      negligible for calculating in-air output ratio, Sc for small and irregular fields
      often used in intensity-modulated radiation therapy (IMRT). An extra-focal source
      model for scattered radiation from MLCs, namely MLC scatter source, has been
      developed to improve the accuracy of the Sc calculation. METHODS: A conventional
      dual-source model was made by using Sc data that were measured for collimator
      defined fields of Varian Clinac IX linear accelerator. Then, an MLC scatter
      source at the center of the MLC position of the linear accelerator was assumed in
      the model. The MLC scatter source model consisted of two Gaussian functions of
      which parameters were iteratively optimized against the Sc data measured for
      different MLC fields with fixed collimator sizes. To evaluate the effectiveness
      of the developed source model, measurements were made for various MLC-defined
      irregular or square fields. The calculated Sc data by using (1) the developed
      source model and (2) the conventional dual source model were compared with the
      measured data. RESULTS: The mean discrepancy between the measured Sc and
      calculated Sc from the developed source model was 0.08+-0.28%, while one from the
      conventional source model was 0.44+-0.39%. CONCLUSIONS: The developed MLC scatter
      source model in conjunction with the dual source model could improve the accuracy
      of the Sc calculation in IMRT fields.

PMID- 28519063
TI  - SU-E-T-03: Justification and Feasibility of Neural Stem Cell Sparing in Whole
      Brain Irradiation Using VMAT.
AB  - PURPOSE: To determine the impact of radiation on neural stem cells and examine
      the feasibility of neural stem cell sparing using volumetric modulated arc
      therapy (VMAT) for whole brain irradiation. METHODS: Murine neural stem cells
      were harvested from the sub-ventricular zone (SVZ), cultured and assessed for
      radio-sensitivity and differentiation potential in response to radiation (0-6Gy).
      Clonogenic survival of these cells was compared to that of tumor cells derived
      from the murine PTEN-/-/Kras+ spontaneous brain tumor model. The differentiation
      potential of neural stem cells surviving irradiation was examined by allowing the
      cells to differentiate for five days and analyzing cell types. In order to
      address the feasibility of neural stem cell sparing, a typical 3D whole brain
      treatment was compared to VMAT, in which the neural stem cell compartment,
      designated and contoured as the lateral ventricles with a 3-5mm margin, was
      spared. Whole brain dose coverage was maintained similarly to conventional 3D
      treatment, while minimizing the dose to the stem cell compartment. RESULTS:
      Neural stem cells are significantly more radio-sensitive than their tumor
      counterparts (2Gy, p=0.018), and the neuronal differentiation capacity of stem
      cells that survive radiation treatment is markedly diminished. Compared to
      conventional 3D treatment, VMAT reduces radiation dose to the stem cell SVZ
      compartment while maintaining adequate coverage of the whole brain. CONCLUSIONS:
      Radiation-induced cognitive decline from whole brain irradiation is of particular
      clinical relevance. Cognitive functions are strongly influenced by the activity
      of neural stem cells, thus stem cell sparing may help mitigate radiation-induced
      cognitive decline. To our knowledge, this is the first study to confirm that
      radiation induces impaired neuronal differentiation at clinically relevant doses,
      and that improved stem cell sparing of the lateral ventricles (SVZ) is feasible
      using VMAT. Thus our studies confirm that VMAT should be examined further for
      clinical relevance in whole brain irradiation.

PMID- 28519064
TI  - SU-E-J-187: Evaluation of the Effects of Dose on 4DCT-Calculated Lung
      Ventilation.
AB  - PURPOSE: To investigate the effects of radiation therapy (RT) treatment dose on
      ventilation. METHODS: Optical flow deformable image registration of the normal
      end-expiration and end-inspiration phases of 4DCT images was used to correlate
      the voxels between the two phases. 4DCT sets from before and after RT were used
      to derive ventilation for 3 SBRT lung patients. Planning dose and normalized
      ventilation were superimposed on the CT volume resulting in each voxel having a
      volume, a normalized ventilation and a dose. From these values a 3D dose
      ventilation-volume surfaces was created. The surface was integrated over dose to
      reduce the 3D surface to a 2D histogram that is easier to interpret. RESULTS: For
      lung tissue regions receiving more than 20 Gy, a decrease in ventilation was
      observed in the three patients. Patient A (time between scans, T=26 months)
      showed an increase in ventilation for regions receiving a dose smaller than 20
      Gy, whereas patients B (T=3 months) and C (T=6 months) did not show any change
      for these regions. Mean ventilation within the 20 Gy region for patient A was
      0.57 before RT and 0.51 after RT; and 0.54 before and 0.48 after RT for the 30 Gy
      region. Mean ventilation for the 20 Gy region for patient B was 0.49 before RT
      and 0.47 after RT, for the 30 Gy region mean ventilation was 0.49 Gy before and
      0.45 Gy after RT. Patient C's mean ventilation for the 20 Gy region was 0.54
      before RT and 0.50 after RT, for the 30 Gy region mean ventilation was 0.54
      before RT and 0.49 after RT. CONCLUSIONS: Ventilation before and after radiation
      therapy can be measured using 4DCT and deformable image registration techniques.
      In a preliminary application of this approach for three patients, changes in
      ventilation were observed with a weak correlation between ventilation change and
      dose. Partially supported by a grant from Varian Medical Systems.

PMID- 28519065
TI  - SU-E-T-14: Modeling of 3D Positron Emission Activity Distributions Induced by
      Proton Irradiation: A Semi-Empirical Method.
AB  - PURPOSE: to present and validate a method for modeling three-dimensional positron
      emission (PE) activity distributions induced by proton beam irradiation for
      PET/CT delivery verification studies in homogeneous media. METHODS: the method
      relies on modeling the 3D proton flux distribution by combining the analytical
      expression for the depth reduction of proton flux with the empirically obtained
      lateral distribution. The latter is extracted from the corresponding dose
      distribution under the assumption that the projectile energy is nearly constant
      in the lateral plane. The same assumption allows calculating the 3D induced
      activity distributions from proton flux distributions by parameterizing the
      energy-dependent activation cross-sections in terms of depth via the energy-range
      relation. Results of this modeling approach were validated against experimental
      PET/CT data from three phantom deliveries: unmodulated (pristine) beam, spread
      out Bragg peak (SOBP) delivery without a range compensator, and SOBP with a range
      compensator. BANG3-Pro2 polymer gel was used as a phantom material because of its
      elemental soft-tissue equivalence. RESULTS: the agreement between modeled and
      measured activity distributions was evaluated using 3D gamma index analysis
      method, which, despite being traditionally reserved for dose distribution
      comparisons, is sufficiently general to be applied to other quantities. The
      evaluation criteria were dictated by limitations of PET imaging and were chosen
      to correspond to count rate uncertainty (6% value difference) and spatial
      resolution (4 mm distance to agreement). With these criteria and the threshold of
      6%, the fraction of evaluated voxels passing the gamma evaluation was 97.9% for
      the pristine beam, 98.9% for the SOBP without compensator, and 98.5% for SOBP
      with compensator. CONCLUSIONS: results of gamma evaluation indicate that the
      activity distributions produced by the model are consistent with experimental
      data within the uncertainties of PET imaging for clinical proton beams
      deliveries. This work was supported by the Bankhead-Coley Florida Biomedical
      Research Program under Grant No. 1BD10-34212.

PMID- 28519066
TI  - SU-E-J-198: Bioluminescence Monitoring of Metastatic Breast Cancer: Quantitative
      Assessment of Radiation Treatment Effects and Tracking of Tumor Cells.
AB  - PURPOSE: To evaluate radiation treatment effects on mammary carcinoma cells,
      quantitative photon radiance were monitored to track light-emitting cancer cells
      and metastasis using in vivo bioluminescence imaging. METHODS: Eight female
      BALB/c mice aged 8 weeks were orthotopically injected with 5*104/cc 4T1 tumor
      cells into the abdominal mammary gland. The firefly luciferase-based
      bioluminescence images were acquired every 2-3 days for 1 month. Bioluminescent
      intensity was analyzed in average surface radiance (photons/sec/cm2 /sr) taken in
      3-dimensional bioluminescence tomography (BLT). After 1 week, single-radiation
      dose of 20 Gy was delivered by orthovoltage X-rays. Variation of detected
      bioluminescence signals emitted from molecular cancer cells was depicted on BLT
      images. To delineate tumor volumes according to bioluminescence intensity on
      anatomical images for radiation therapy, BLT images were registered with the
      micro computed tomography (CT) images using surface-constrained warping. RESULTS:
      Multispectral BLT images elaborated on early detection of cancer cells,
      characteristics of tumor growth, and metastasis for more accurate determination
      of internal bioluminescent sources. The radiation-treated mice having only
      primary tumor volumes showed 67% decrease in bioluminescent signals, while the
      mice with metastatic cancer cells suggested 88% reduction, as compared to the
      control group. Registration of BLT with CT images guided molecular cancer cells
      on anatomical coordinates. CONCLUSIONS: The BLT imaging was a useful tool to
      localize cancer cells and to quantify radiation response. Application of BLT led
      to more accurate definition of tumor volumes including molecular probe-based
      microscopic cancer cells. Monitoring of bioluminescence signals enables to
      diagnose real-time metastatic behavior of cancer cells and determine optimal
      radiation treatment strategies adapted to tumor characteristics.

PMID- 28519067
TI  - SU-E-T-24: Development and Implementation of an Automated Algorithm to Determine
      Radiation Isocenter, Radiation vs. Light Field Coincidence, and Analyze Strip
      Tests.
AB  - PURPOSE: The aim of this study was to develop a phantom and analysis software
      that could be used to quickly and accurately determine the location of radiation
      isocenter using the Electronic Portal Imaging Device (EPID). The phantom could
      then be used as a static reference point for performing other tests including:
      radiation vs. light field coincidence, MLC and Jaw strip tests, and Varian
      Optical Guidance Platform (OGP) calibration. METHODS: The solution proposed uses
      a collimator setting of 10*10 cm to acquire EPID images of the new phantom
      constructed from LEGO(r) blocks. Images from a number of gantry and collimator
      angles are analyzed by the software to determine the position of the jaws and
      center of the phantom in each image. The distance between a chosen jaw and the
      phantom center is then compared to the same distance measured after a 180 degree
      collimator rotation to determine if the phantom is centered in the dimension
      being investigated. The accuracy of the algorithm's measurements were verified by
      independent measurement to be approximately equal to the detector's pitch. Light
      versus radiation field as well as MLC and Jaw strip tests are performed using
      measurements based on the phantom center once located at the radiation isocenter.
      RESULTS: Reproducibility tests show that the algorithm's results were objectively
      repeatable. Additionally, the phantom and software are completely independent of
      linac vendor and this study presents results from two major linac manufacturers.
      An OGP calibration array was also integrated into the phantom to allow
      calibration of the OGP while the phantom is positioned at radiation isocenter to
      reduce setup uncertainty contained in the calibration. CONCLUSIONS: This solution
      offers a quick, objective method to perform isocenter localization as well as
      laser alignment, OGP calibration, and other tests on a monthly basis.

PMID- 28519068
TI  - Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial-Mesenchymal
      Transition in Osteosarcoma by Regulating the miR-221/ARHI Pathway.
AB  - Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles
      in the development of human cancers. The lncRNA growth arrest-specific 5 (GAS5)
      is reported to be a tumor suppressor in multiple cancers. However, the roles of
      GAS5 and its related miRNAs in osteosarcoma are poorly understood. This study
      explored the potential functions and mechanisms of GAS5 in the tumorigenesis of
      osteosarcoma. Here, the expression of GAS5, miR-221 and aplasia Ras homologue
      member I (ARHI) was determined in osteosarcoma tissues and cells by Real-time PCR
      (RT-qPCR). The underlying mechanism of GAS5 in osteosarcoma growth was analyzed
      via MTT, Transwell, RT-qPCR, Western blot, dual-luciferase reporter assay, RNA
      immunoprecipitation, and xenograft models after GAS5 overexpression. GAS5 and
      ARHI levels were significantly reduced, while miR-221 increased, both in
      osteosarcoma tissues and cells. Overexpression of GAS5 suppressed the
      proliferation, migration, and epithelial-mesenchymal transition (EMT) of
      osteosarcoma cells. GAS5 could directly bind to miR-221 to decrease miR-221
      expression and enhance ARHI expression. The effect of GAS5 overexpression on the
      proliferation, migration and EMT was reversed by miR-221 mimics or ARHI siRNA in
      osteosarcoma cells. Additionally, GAS5 suppressed tumor volume, Ki-67 and PCNA
      staining, and EMT process in the development of osteosarcoma in vivo. Taken
      together, lncRNA GAS5 functions as a competing endogenous RNA for miR-221 to
      suppress cell growth and EMT in osteosarcoma by regulating the miR-221/ARHI
      pathway. J. Cell. Biochem. 118: 4772-4781, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28519244
TI  - Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies.
AB  - Substance use among pregnant women is a major public health issue. Both
      prescription opioid use and illicit opioid abuse have increased dramatically in
      recent years. Prolonged in utero drug exposure may result in neonatal abstinence
      syndrome (NAS), an acute multisystemic clinical entity that occurs in the first
      days of life. This syndrome is caused by abrupt discontinuation of fetal exposure
      to licit or illicit drugs chronically consumed by the mother during pregnancy and
      transmitted to the fetus through the placenta. It usually requires prolonged
      hospitalization and may have long-term effects. The interplay of many factors
      contributes to its clinical heterogeneity, and its pathophysiology has not been
      fully unveiled. The first step in NAS management consists of nonpharmacologic
      interventions and includes promoting breastfeeding when not contraindicated. If
      withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring
      system supports care providers across the pharmacotherapy process from initiation
      through the monitoring phase, until weaning and discontinuation. However, a
      standardized approach to pharmacotherapy is still lacking. Morphine is usually
      the first-line agent to treat NAS. Methadone is a valid option, but its safety
      profile is not completely known. Phenobarbital, despite its lack of effect on
      gastrointestinal symptoms and unfavorable pharmacologic features, has been
      identified as a second-line agent to be used in infants unresponsive to opiates.
      Although buprenorphine and clonidine seem promising, their use requires further
      validation. Long-term developmental effects of NAS therapy call for more
      comprehensive, longitudinal assessments. In this article, key points for use of
      recommended therapies are outlined, and directions for future research are
      suggested.

PMID- 28519481
TI  - SU-E-I-35: Experience with Th Zero Gravity Suit.
AB  - PURPOSE: To compare the effectiveness of the Zero Gravity Suit (CFI Medical
      Solutions) in reducing the annual dose received by one physician in the Cardiac
      Catheterization Lab. METHODS: A physician with a history of receiving high annual
      dose equivalents was purchased a Zero Gravity Suit. Film badges (Landauer) were
      worn at the collar and waist and monitored monthly. Previous dose history was
      acquired via the Landauer Exposure Report Archive. Annual values for Deep Dose
      Equivalent (DDE), Eye Dose Equivalent (LDE), and Shallow Dose Equivalent (SDE)
      were compared for the first full year of the Zero Gravity Suit (2011) to the
      previous four years (2007-2010). Readings for 2009 and 2007 were corrected for
      improper wear of the film badges. RESULTS: The reduction in dose equivalent for
      DDE ranged from 70%-87%. The reduction in dose equivalent for LDE ranged from 16%
      60%. The reduction in dose equivalent for SDE ranged from 16%-60%. CONCLUSIONS:
      It was determined that the Zero Gravity Suit is effective at reducing the
      exposure of a physician with a history of high annual dose equivalents in our
      facilities Cardiac Catheterization Lab. While the suit did reduce the LDE and SDE
      it was more effective at reducing the DDE. During 2010 the suit was acquired
      midyear. The dose equivalent values would likely be similar to 2011 if the suit
      was introduced at the beginning of the year. In 2009 the physician was pregnant
      and attempting a reduced workload. The physician only uses the suit if a
      procedure is expected to take longer than fifteen minutes. The accuracy of the
      study is dependent upon the physician wearing the badges consistently and
      correctly and the physician using the Zero Gravity Suit consistently.

PMID- 28519482
TI  - SU-E-I-07: Proposal for a Novel Algorithm of Effective Dose Evaluation for
      Medical Radiation Exposure.
AB  - PURPOSE: The validity of effective dose (ED) in medical applications, which
      mostly involving partial-organ irradiation, has long been argued. We now propose
      a new algorithm of effective dose evaluation for medical radiation exposure. The
      new algorithm will include new Relative Volume Factors, or RVFs, to account for
      the relative irradiated volume of the partially-irradiated organs, such as skin
      and bone marrow. METHODS: To validate the proposed algorithm, three ED evaluation
      methods were applied to five neuro-imaging protocols of a C-arm cone-beam CT: 1)
      MOSFET-anthropomorphic- phantom measurement for organ doses, ED evaluated with
      the original ICRP algorithm; 2) using the same MOSFET-measured organ doses, ED
      evaluated with the new algorithm; and 3) Monte Carlo (PCXMC, developed by STUK)
      dose estimation as gold standard. RESULTS: For all five imaging protocols, the ED
      evaluations by the new algorithm agreed very well with the Monte Carlo simulation
      results (within 10% difference), whereas the original ICRP algorithm
      overestimated EDs by approximately a factor of 2. CONCLUSIONS: The proposed
      algorithm provides a more accurate estimation of ED in medical exposures than the
      original ICRP algorithm. It potentially establishes the ED as a more reasonable
      index for cross-protocol dose comparison.

PMID- 28519483
TI  - SU-E-I-56: Threshold Effect of ASIR Before Which Image Improve and After Which
      Image Degrades.
AB  - PURPOSE: This study showed to what extent ASIR improves CT-image and to what
      extent it degrades it. METHODS: In our study we used GE HD750 CT-scanner, Siemens
      Sensation CT-scanner, Catphan, PTW-pin-ion- chamber, CTDI-phantom. We measured
      the CT-dose using the PTW-pinion-chamber and CTDI-phantom. Image-quality and
      noise were evaluated using catphan and GE water phantom. RESULTS: Image noise
      reduce as higher levels of ASIR are applied. A phantom scan showed that 50%ASIR
      with 50% lower-dose (10.8mGy) achieved the same image noise of standard FBP image
      with full dose 21.7mGy (noise~5). To confirm that the two same-noise images
      retain same image-quality, two scans were compared; one with full dose
      260mAs(21.7mGy) and the other one with 50% lower dose 130mAs(10.8mGy). The
      results showed that ASIR failed to retain the same quality. For high contrast
      resolution, 50%ASIR reduced the resolution of patterns = 71p/cm, however it
      improved the detectability of patterns = 61p/cm. ASIR has degraded the CNR of the
      low-contrast-objects of = 5HU (CNR of 1.4 at 260mAs STND to CNR of 1.08 at 130mAs
      ASIR), however it improved the CNR of the low-contrast-objects of = 10HU (CNR of
      2.35 at 260mAs STND to CNR of 2.63 at 130mAs ASIR). ASIR degraded the edges and
      killed some of the small objects. This shows that ASIR has a critical point of
      improve/degrade. Also, ASIR can improve images for the same dose, but with high
      levels of ASIR (e.g. 100%ASIR), cause disapear of small low contrast objects
      (e.g. 2mm). CONCLUSIONS: People think that ASIR only improves image and reduces
      patient dose. Our study showed that ASIR has some drawbacks. There is a threshold
      before wich ASIR is positive and after which ASIR is negative. Recently only GE
      provide ASIR in the market but our study showed that other CTs such as Siemens
      can do similar performance like ASIR.

PMID- 28519484
TI  - SU-E-I-28: Development of Graphic Patient Models for a Real-Time Skin Dose
      Tracking System (DTS) for Fluoroscopic Interventional Procedures.
AB  - PURPOSE: To develop a library of graphic human models that closely match patients
      undergoing interventional fluoroscopic procedures in order to obtain an accurate
      estimate of their skin dose. METHODS: A dose tracking system (DTS) has been
      developed that calculates the dose to the patient's skin in real time during
      fluoroscopic procedures based on a graphical simulation of the x-ray system and
      the patient. The calculation is performed using a lookup table containing values
      of mGy per mAs at a reference point and inverse-square correction using the
      distance from the source to individual points on the skin. For proper inverse
      square correction, the external shape of the graphic should closely match that of
      the patient. We are in the process of developing a library of 3D human graphic
      models categorized as a function of basic body type, sex, height and weight. Two
      different open- source software applications are being used to develop graphic
      models with varying weights and heights, to 'morph' the shapes for body type and
      to 'pose' them for proper positioning on the table. The DTS software is being
      designed such that the most appropriate body graphic can be automatically
      selected based on input of several basic patient dimensional metrics. RESULTS: A
      series of male and female body graphic models have been developed which vary in
      weight and height. Matching pairs have been constructed with arms at the side and
      over the head to simulate the usual placement in cardiac procedures. The error in
      skin dose calculation due to inverse-square correction is expected to be below 5%
      if the graphic can match the position of the patient's skin surface within 1 cm.
      CONCLUSIONS: A library of categorized body shapes should allow close matching of
      the graphic to the patient shape allowing more accurate determination of skin
      dose with the DTS. Support for this work was provided in part by NIH grants
      R43FD0158401, R44FD0158402, R01EB002873 and R01EB008425, and by Toshiba Medical
      Systems Corporation.

PMID- 28519485
TI  - SU-E-E-05: An Educational Physical Environment Concept with Close Research and
      Clinical Collaborations.
AB  - PURPOSE: To create a physical environment where imaging medical physicists can be
      educated in a real-work, clinical and research setting in close collaboration
      with professionals such as physicians, biomedical engineers, and other medical
      personnel. METHODS: A single building structure has been designed where medical
      physics students can be immersed in a collaborative clinical and research
      educational environment. RESULTS: A Clinical Translational Research Center has
      been constructed on the top four floors over a new Global Vascular Institute
      (GVI) which is connected to the main university hospital complex and adjacent to
      radiation therapy facilities. The research and educational component including
      offices, labs, and conference rooms for the Medical Physics Program is on the top
      floor and dedicated research imaging suites (fluoroscopic interventional systems,
      CT, PET/CT, and MRI) along with complete animal facilities and additional
      research labs for cardiac and vascular investigators are on the two top floors.
      An atrium and numerous meeting spaces are in place to encourage informal
      communication among students and science and clinical investigators. The clinical
      GVI, which occupies the lower four floors, has a full upper floor containing 15
      vascular imaging suites for cardiac, neuro, and peripheral vascular imaging and
      interventions while the floors below have short-term hotel-like patient and
      family rooms favoring ambulatory patients having minimally invasive procedures.
      Medical physics didactic education is designed to take place in modern meeting
      rooms; however, because of the close proximity to research labs and clinical
      suites, students are expected to get a unique perspective on how research is done
      and how it is translated into clinical practice. CONCLUSIONS: A new physical
      structure has been built which enables medical physics education to be an
      integral part of a highly collaborative clinical translational research
      environment. Research funds provided by NIH grants and equipment grants from
      Toshiba Medical Systems Corp.

PMID- 28519486
TI  - SU-E-I-39: Intensive Monitoring of System Performance and Protocols on CT
      Systems.
AB  - PURPOSE: The regulatory response to the recent CT overdoses is still in the
      process of being implemented. The more action taken before the regulations take
      effect reduces the exposure of the institution to medical and legal problems.
      Therefore, eighteen months ago we implemented an intensive QC program to ensure
      CT safety. The first component was to monitor the dose and SNR produced by a
      single CT examination weekly to identify changes. The second was to monitor
      changes in the protocols. METHODS: We measured the CTDI and SNR for the routine
      head examination. We developed a script to identify and log changes in any of the
      234 protocols. RESULTS: Surprisingly, there were many changes to the protocols:
      on one unit 388 protocols were changed on 26 dates over the 18 month period. The
      reasons included: protocol optimization, scanner service, software reloads,
      mistakes, mistakenly loading the protocols from another section's scanner. The
      standard deviation of the CTDI was 2% to 3%. The dominant source of variation was
      probably positioning. The standard deviation of the SNR was 4% to 9%. The entire
      procedure requires 30min to 50min to test five CT scanners each week.
      CONCLUSIONS: The standard deviations of the CTDI values and of the SNR values are
      sufficiently small to allow anomalies to be identified using these relatively
      simple methods. Frequent protocol checking is an important component to any QC
      program.

PMID- 28519487
TI  - SU-E-I-11: A Novel High Resolution CT Imager for a Breast SPECT-CT System.
AB  - PURPOSE: To evaluate the intrinsic characteristics of a new high resolution,
      large area, small bezel, digital imager developed for a dedicated SPECT-CT system
      for fully-3D mammotomographic imaging applications. METHODS: A new flat panel
      digital imager was developed having 127MUm pixels (identical to those in the
      Paxscan 2520) with an active 40*30cm area and 3200*2304 total pixels, which is
      well suited for pendant breast imaging close to the chest wall. The readout and
      driver ASIC TAB bonding pads were arranged on only two sides of the imager plate,
      to eliminate dead edge spacing. A special housing was developed to accommodate
      this imaging plate providing very narrow 8mm edges (bezels) on two orthogonal
      sides The TFT array imager was coated with 600MUm thick micro-columnar CsI, which
      provides >90% absorption in the breast CT (60-80kVp) x-ray energy range. It
      provides better than 70% absorption for RQA5 (70kVp 21mm Al filter) x- ray
      radiation. The readout ASICs are connected to 14 bit A/D converters, and special
      readout ASICs with gain switching feature, which provide an additional 4bit
      virtual (2-3 effective) dynamic range. RESULTS: The MTF is ~7.5% at the 3.9 lp/mm
      Nyquist frequency. The NPS curves continuously decrease with increasing spatial
      frequencies, characteristic of scintillator based imagers. The excellent DQE (0)
      measured at RQA5 is ~75% in the 0.1-1mR dose range and ~10% at the Nyquist
      frequency. The imager has excellent linearity over the full dynamic range, and
      high contrast images are readily acquired. CONCLUSIONS: The new 4030 flat panel
      imager is a high resolution, state of the art detector, ideal for breast imaging
      and other applications. This detector is included in the SPECT-CT device in
      development.

PMID- 28519488
TI  - SU-E-I-49: Influence of Scanner Output Measurement Technique on KERMA Ratios in
      CT.
AB  - PURPOSE: KERMA ratios (RK) are defined as the ratio of KERMA measured at a
      specific phantom location (K) to in-air isocenter CT scanner output (KCT). In
      this work we investigate the impact of measurement methodology on KCT values.
      METHODS: OSL dosimeter chips were used to measure KCT for a GE VCT scanner (GE
      Medical Systems, Waukesha WI), using the 40 mm nominal beam width. Methods
      included a single point measurement at the center of the beam (1 tube rotation),
      and extended z-axis measurements using multiple adjacent OSL's (7.5 cm extent),
      with single tube rotation, multiple contiguous axial scans, and helical scans
      (pitch of 1.375). Measurements were made in air and on the scan table at 80 and
      120 kV. RESULTS: Averaged single point measurements were consistent, with a mean
      coefficient of variation of 2.5%. For extended measurements with a single tube
      rotation, the mean value was equivalent to the single point measurements. For
      multiple contiguous axial scans, the in-air KCT values were higher than the
      single rotation mean value and single point measurements by 13% and 10.3% at 120
      and 80 kV, respectively, and for the on-table measurements the values were 14.9%
      and 8.1% higher at 120 and 80 kV, respectively. The increase is due to beam
      overlap caused by z- axis over-beaming. Extended measurements using helical
      scanning were equivalent to the multiple rotation axial measurements when
      corrected for the helical pitch. For all methodologies, the in-air values
      exceeded the on- table measurements by an average of 23% and 19.4% at 80 and 120
      kV, respectively. CONCLUSIONS: Scanner KCT values must be measured to allow organ
      dose estimation using published RK values. It is imperative that the KCT
      measurement methodology is the same as for the published values, or large errors
      may be introduced into the resulting organ dose estimates.

PMID- 28519489
TI  - SU-E-I-21: Effect of Different Fluorescent Lights with Various Colors of a
      Reading Room on Chromaticity of LCD.
AB  - PURPOSE: To examine variation of chromaticity of LCD in different types of
      fluorescent lights in a reading room. METHODS: A color LCD (RX320, antiglare
      type, 450 cd/m2 , three-megapixel, Eizo Nanao), and a monochrome LCD (G31-S, anti
      glare type, 450 cd/m2 , three-megapixel, Eizo Nanao) were used in this study. The
      chromaticity in grayscale images with eighteen luminance levels were measured
      under five types of fluorescent lights with different color spectrums (Daylight:
      6,700 K, Natural white: 5,000 K, White: 4,200 K, Warm white: 3,500 K, Light bulb:
      3,000 K) by using a colorimeter (CS-200: KONICA MINOLTA). The chromaticity of
      LCDs was measured at various ambient lighting conditions (a dark room, 36, and
      300 lux) and different types of fluorescent lights. RESULTS: The chromaticity of
      LCDs measured under ambient lights was changed from that measured in a dark room.
      The chromaticity of LCDs varied with different types of fluorescent lights. As
      illuminance of the room increased, variations in chromaticity at relatively lower
      luminance levels increased. The direction of changes in chromaticity shifted to
      the color for each fluorescent light. CONCLUSIONS: Fluorescent lights having
      different color spectra affect the chromaticity of LCDs.

PMID- 28519490
TI  - SU-E-I-32: Sterile Radiation Reduction Gloves May Be Contraindicated in
      Fluoroscopically Guided Interventions.
AB  - PURPOSE: Sterile radiation reduction gloves have been widely used in the past
      decade to provide modest decreases in operator hand dose when the hands are
      placed in the field of view (FOV). While multiple publications have quantified
      the potential dose reduction from the use of such gloves, possible effects on the
      patient have not yet been assessed. The aim of this study was to determine if
      radiation reduction gloves can Result in a significant increase in patient dose
      and increased risk of radiation induced skin injury when used in interventional
      radiology. METHODS: The effect of radiation reduction gloves when used in the FOV
      was determined by measurement of patient entrance exposure rate (EER) for a
      variety of patient sizes and varying operating and magnification modes. EERs were
      measured with no glove in the FOV, with one glove and, to replicate the actions
      of many dose-conscious radiologists, with double gloves in the FOV. RESULTS:
      Compared to an ungloved hand, the use of a single radiation reduction glove near
      the center of the FOV results in a 2-fold average increase in patient EER. The
      use of double radiation reduction gloves results in a 3-fold average increase in
      EER. In both cases, this increase was only weakly dependent on the size of the
      patient and on the operating and magnification modes used. In fact, patient
      thicknesses ranging from 6-14 inches and operating modes ranging from low-dose
      fluoroscopy to DSA produced less than a 20% deviation from the increases in EER
      quoted above. CONCLUSIONS: When used in the FOV, radiation reduction gloves can
      substantially increase patient EER. This increase in patient dose, when compared
      with the relatively small published reduction in extremity dose provided to the
      operator, may make their use contraindicated in cases where radiation induced
      skin injury is a possible risk.

PMID- 28519491
TI  - SU-E-I-04: Implementation of a Fast Monte Carlo Scatter Correction for Cone- Beam
      Computed Tomography.
AB  - PURPOSE: To improve image quality in cone-beam computed tomography (CBCT) scans
      by implementation of a fast and accurate MC-based scatter correction algorithm.
      METHODS: A Solid WaterTM phantom was imaged on a Varian OBI CBCT scanner using
      the standard-dose head protocol (100 kVp, 151 mAs, partial-angle). A fast Monte
      Carlo simulation developed in the EGSnrc framework was used to transport photons
      through the uncorrected CBCT scan. From the simulation output, the contribution
      from both primary and scattered photons for each projection image was estimated.
      Using these estimates, a subtractive scatter correction was performed on the CBCT
      projection data. This correction procedure was repeated iteratively, using the
      previous scatter corrected scan as input to the Monte Carlo simulation. RESULTS:
      Implementation of the scatter correction algorithm on real CBCT data was shown to
      help mitigate scatter-induced artifacts, such as cupping and streaking. The
      scatter corrected images were also shown to have improved accuracy in
      reconstructed attenuation coefficient values. In a region of interest centered on
      the Solid Water phantom, the number of voxels agreeing to within 10% of the
      theoretical attenuation coefficient increased from 46% to 97% after two
      iterations of the scatter correction. CONCLUSIONS: These results suggest that the
      proposed scatter correction algorithm is successful in improving image quality in
      real CBCT images. The accuracy of the attenuation coefficients extracted from the
      corrected CBCT scan renders the data suitable for on-the-fly dose recalculations,
      as well as vastly improved image registration.

PMID- 28519492
TI  - SU-E-I-43: Reducing Scanogram Dose Without Affecting the Planned Tube Current
      Modulation of a Diagnostic Abdomen/pelvis CT Scan.
AB  - PURPOSE: In tube current modulated CT scans, scanograms (localizer radiographs)
      are needed prior to the diagnostic scan to obtain the attenuation properties of
      each patient which is then used to plan the mA modulation of the diagnostic scan.
      The purpose of this study was to investigate whether lowering the dual-scanogram
      dose affects the mA modulation scheme. Although scanograms use relatively low
      dose, the goal of this study is to reduce radiation dose from scanograms even
      further in keeping with the ALARA principle. METHODS: Abdomen-pelvis CT exams
      were performed on an anthropomorphic phantom (Pixy RS102 phantom, Radiology
      Support Devices) using a Toshiba Aquilion CT scanner with SUREExposure tube
      current modulation. Various combinations of kVp and mAs were used to acquire dual
      scanograms (AP and lateral); parameters for the diagnostic scan following the
      scanograms were fixed. For each kVp, the mA was reduced in intervals from a
      baseline 100% mA level, including 80%, 60%, 40%, 20% of the baseline, and a
      minimum level of 10mA. For each exam the resulting CTDIvol and total mAs were
      compared. RESULTS: When scanogram kVp was reduced from 120kVp (default) to 100kVp
      and 80kVp, both CTDIvol and total mAs of the diagnostic scan increased slightly
      (up to 4.3%). When scanogram mA was decreased in intervals representing 80%, 60%,
      40%, and 20% of baseline, there was little to no effect (less than 3%) on CTDIvol
      and total mAs for the diagnostic scan. For the minimum mA scanograms, CTDIvol was
      affected by up to 5.5% and total mAs was affected by up to 6.1% (at 80kVp). It
      should be noted that for 120kVp, the decrease of both CTDIvol and total mAs was
      within 1% at all reduced scanogram dose levels. CONCLUSIONS: It was suggested to
      use the default 120kVp scanogram to minimize the dose from the diagnostic scan.
      However, the mA of dual-scanograms may be significantly reduced without affecting
      planned mA of the exam.

PMID- 28519493
TI  - SU-E-I-15: Comparison of State-Of-The-Art Interpolation-Based Metal Artifact
      Reduction (MAR) Algorithms for Cone-Beam Computed Tomography (CBCT).
AB  - PURPOSE: To compare four metal-artifact-reduction (MAR) algorithms in their
      ability to correct the typical streaking artifacts that appear in cone- beam
      computed tomography (CBCT) images. METHODS: The goal was to compare the strengths
      and weaknesses of four MAR algorithms, Basic; Wei; Mazin and Meyer, using typical
      clinical situations where metal is present. Three clinical situations were
      evaluated: fiducial markers in the abdomen; hip implants and multiple dental
      fillings. The algorithms take original CBCT projections as input and produce a
      corrected image. The location of the metal is identified in the CBCT images and a
      forward projection identifies which pixels in the projections need to be replaced
      by interpolation of neighboring pixels. The three advanced algorithms extend the
      Basic technique with more sophisticated interpolation schemes. Wei and Meyer
      identify the high contrast structures using image segmentation in order to reduce
      their appearance in the projections before interpolation. Mazin corrects the
      original projections using a forward projection of the Basic correction. RESULTS:
      All the algorithms reduced the streak artifacts typical of metal structures.
      Nevertheless, depending upon the clinical task, the algorithms also added shading
      and streaks which reduced the overall visual impression. Images containing
      fiducial markers in the abdomen showed obvious improvements; images containing
      hip implants were improved but also showed distracting shading artifacts; and,
      images with multiple dental fillings all appeared visually worse than the
      uncorrected images. In almost all cases, Mazin outperformed the other approaches
      and introduced the fewest additional streaks and shading artifacts. CONCLUSIONS:
      This work indicates that the Mazin algorithm is best suited for clinical usage of
      MAR. Furthermore the algorithm is fairly simple and can be computational very
      efficient making it well suited for clinical use. Nevertheless, the overall
      improvement is highly dependent on the individual characteristics of the original
      image. For dental implants no correction is recommended.

PMID- 28519494
TI  - SU-E-I-53: Optimal KVp for Image Quality and Noise in Iodine Contrast in Head
      CTA.
AB  - PURPOSE: For brain CT perfusion it is well established that 80 kVp is optimal.
      Although neuro-CT angiography is somewhat similar, emphasis is on the detection
      of aneurysms and related vascular pathologies throughout the brain. Thus it is
      necessary to visualize small and large blood vessels with contrast material, as
      well as form multi-planar views and 3D images, so image quality and noise in
      addition to contrast are important for thin slices. A study was initiated to
      determine the optimal kVp for neuro-CTA. METHODS: A customized version of a
      commercial head phantom (CIRS 007TE-27 medium adult head CT dose phantom) was
      purchased to facilitate quantitative measurements with iodinated contrast
      material, contrast for white and gray matter, and to maintain the ability to
      perform dosimetry. The customization consisted of adding four 25 mm holes, 35 mm
      from the center arranged at 45 degree angles from the center, with solid rods
      equivalent with brain, white, and gray matter, as well as four fillable vials
      were included for study of contrast agents. Dosimetry measurements were carried
      out with standard pencil chamber and with 0.6 cc ionization chamber. For study of
      the optimal kVp for a head CTA, the vials were filled with four different
      concentrations of contrast, approximating low to medium concentrations that would
      be expected in such a study. The standard CTA protocol was followed, 64 * 0.625,
      pitch 0.53, rotation speed 0.5 second, and CTDIvol was kept constant for each
      kVp. RESULTS: The best contrast was observed at 80 kVp; however, in order to
      achieve noise in CTA low enough to be clinically useful there may be issues with
      tube current capability for a clinical technique. Clinical investigation is
      underway. CONCLUSIONS: The best balance of contrast and noise currently possible
      will be achieved at 100 kVp in a clinical scan.

PMID- 28519495
TI  - SU-E-I-06: Measurement of Skin Dose from Dental Cone-Beam CT Scans.
AB  - PURPOSE: To directly measure skin dose using point-dosimeters from dental cone
      beam CT (CBCT) scans. To compare the results among three different dental CBCT
      scanners and compare the CBCT results with those from a conventional panoramic
      and cephalomic dental imaging system. METHODS: A head anthropomorphic phantom was
      used with nanoDOT dosimeters attached to specified anatomic landmarks of selected
      radiosensitive tissues of interest. To ensure reliable measurement results, three
      dosimeters were used for each location. The phantom was scanned under various
      modes of operation and scan protocols for typical dental exams on three dental
      CBCT systems plus a conventional dental imaging system. The Landauer OSL nanoDOT
      dosimeters were calibrated under the same imaging condition as the head phantom
      scan protocols, and specifically for each of the imaging systems. Using nanoDOT
      dosimeters, skin doses at several positions on the surface of an adult head
      anthropomorphic phantom were measured for clinical dental imaging. RESULTS: The
      measured skin doses ranged from 0.04 to 4.62mGy depending on dosimeter positions
      and imaging systems. The highest dose location was at the parotid surface for all
      three CBCT scanners. The surface doses to the locations of the eyes were ~4.0mGy,
      well below the 500mGy threshold for possibly causing cataract development. The
      results depend on x-ray tube output (kVp and mAs) and also are sensitive to SFOV.
      Comparing to the conventional dental imaging system operated in panoramic and
      cephalometric modes, doses from all three CBCT systems were at least an order of
      magnitude higher. No image artifact was caused by presence of nanoDOT dosimeters
      in the head phantom images. CONCLUSIONS: Direct measurements of skin dose using
      nanoDOT dosimeters provided accurate skin dose values without any image
      artifacts. The results of skin dose measurements serve as dose references in
      guiding future dose optimization efforts in dental CBCT imaging.

PMID- 28519496
TI  - SU-E-I-45: Measurement of CT Dose to An HDPE Phantom Using Calorimetry: A
      Feasibility Study.
AB  - PURPOSE: Radiation dose in CT is traditionally evaluated using an ionization
      chamber calibrated in terms of air kerma in a phantom of specific dimensions. The
      radiation absorbed dose, J/kg, can also be realized directly by measuring the
      temperature rise in the medium. We investigate using this primary method to
      determine the CT dose at a point (a few mm), using the recently proposed (APMM
      TG220) high density polyethylene (HDPE) phantom as a medium. METHODS: The
      calorimeter detection scheme is adapted from the second generation NIST water
      calorimeter using sensitive thermistors in a Wheatstone bridge powered by a lock
      in amplifier. The temperature sensitivity is about 3 microK. The expected
      temperature rise in PE is about 0.6 mK per Gy. The thermistor sensors were placed
      inside a 26 cm dia. * 10 cm HDPE phantom. Two preliminary tests were made: at a
      linear accelerator with a 6 MV photon beam, and at a 16-slice CT scanner with a
      120 kV beam, each with the thermal sensor and with a calibrated ionization
      chamber. RESULTS: The 6 MV photon beam with 10 on/off cycles at 60 s each yielded
      the (uncorrected) run-to-run average dose of 3.06 Gy per cycle (sdm 0.3%), about
      8% higher than the Result from the ionization chamber (calibrated in terms of
      absorbed to water). The CT measurements were also made in the middle section of
      the TG200 30 cm phantom. Twenty consecutive axial scans at 250 mA, which delivers
      a nominal accumulated dose (CTDIvol) of 705 mGy in 50 s at three axial and three
      radial locations were measured. The accumulated dose measured by the ionization
      chamber at the center of the smaller phantom was 347 mGy. CONCLUSIONS: The
      calorimeter data show qualitative tracking of the chamber measurements. Detailed
      thermal and electrical analysis of the system are planned to obtain quantitative
      results.

PMID- 28519497
TI  - SU-E-I-17: Characterization of Rotating Source MicroCT for Evaluating in Vivo
      Murine Trabecular Bone.
AB  - PURPOSE: The objective of this study is to determine the optimal physical
      parameters of the Inveon Multi-modality microCT to assess the trabecular bone of
      mice. METHODS: The x-ray Source-to-Axis Distance is increased from 100mm to 183mm
      to 263mm. Similarly, combining local pixels, or binning, is examined from no
      binning to 2 to 4. Energy is varied from 40kVp to 80kVp in 10kVp increments and
      filter thickness is changed from no filtration to 1.5mmAl in 0.5mmAl increments.
      A lucite phantom with six different density-equivalent rods is used to measure
      changes in Hounsfield Units (HU) and calibrate Bone Mineral Density estimation.
      Mice are scanned at four different magnification and binning combinations to
      evaluate dose and microstructure changes of high to low resolution images.
      RESULTS: An increase in magnification and decrease in binning results in an
      effective pixel size ranging from 95MUm to 9MUm. This decreases the signal to
      noise ratio from 19.2 to 1.7HU and density estimation from 1585 to 1383mg/cc for
      1250mg/cc equivalent material. Increasing the average energy of the radiation
      beam also decreases HU estimation from 1466HU to 1132HU. Higher resolution scans
      extend the scan time and absorbed dose from 5.1 to 13.4min and 3.9 to 125cGy
      respectively. An 18 micron pixel provides distinguishable trabecular bone surface
      from cortices with a 4.2HU signal to noise ratio. CONCLUSIONS: A high
      magnification, binning of 2, 80kVp beam with a 0.5mmAl filter are the optimal
      parameters to evaluate the trabecular bone of mice for the Inveon MM microCT
      unit. This work was supported by the National Institute of Health grants
      (1R01CA154491- 01, 1R03AR055333-01A1 and 1K12-HD055887-01). This work was also
      supported by PHS Cancer Center Support Grant P30 CA77398. This work was also
      supported by PHS Cancer Center Support Grant P30 CA77398. Susanta K Hui is a
      scholar of the BIRCWH (Building Interdisciplinary Careers in Women's Health)
      program. Luke Arentsen is supported by the Grant in Aid funding from the
      Universit.

PMID- 28519498
TI  - SU-E-I-55: Cumulative Radiation Exposure and Cancer Risk Estimates in Pediatric
      Hydrocephalus Patients Undergoing Repeat Or Multiple CT.
AB  - PURPOSE: Children with a shunt for hydrocephalus often undergo multiple follow-up
      head CT scans, increasing the risk for long-term effects of ionizing radiation.
      The study is to define a conservative estimate of frequent CT head scans for
      pediatric patients with a shunt for hydrocephalus and to quantify their
      cumulative CT radiation doses and lifetime attributable risk of developing
      cancer. METHODS: All children at age of less than 17 years with a shunt for
      hydrocephalus who underwent non-enhanced head CT at a tertiary hospital between
      2007 and 2011 were identified and categorized by total number of scans per study
      period as non-frequently (<3), or frequently (>=3) scanned. We retrospectively
      identified the number of CT head scans, dose length product (DLP) and the applied
      scan parameters according to age, gender and study time. Effective doses were
      estimated using age- specific DLP to effective dose conversion coefficients.
      Lifetime attributable cancer risk was then estimated based on the BEIR VII.
      RESULTS: During the 5-year study period, a total of 264 children (mean age, 5.5
      years; range less than one month to 17 years; 146 boys and 118 girls) underwent
      747 CT head scans, of whom 100 patients (41.7%) were frequently scanned. The
      median and mean of frequently scans are 4 and 5.33, with the most frequently
      scanned patient underwent 34 CT head scans from birth to 4 years and 1 month age.
      The average effective dose was 15.71 mSv, ranging from 3.65 mSv to 64.70 mSv. The
      estimated lifetime attributable cancer risk is one in 637, ranging from one in
      2739 to one in 155, based on the standardized BEIR VII conversion of 0.0001/mSv.
      CONCLUSIONS: The children with shunts have a substantially increased risk of
      developing cancer from cumulative CT radiation exposure.

PMID- 28519499
TI  - SU-E-I-27: Effect of Focal Spot Choice on the System Performance of a High-
      Resolution Micro-Angiographic Fluoroscope (MAF) Detector.
AB  - PURPOSE: The generalized metrics of GMTF and GDQE were used to evaluate the
      effect of focal-spot choice on system performance of the Micro- Angiographic
      Fluoroscope (MAF) imager with a geometric magnification common for neuro
      endovascular interventions. METHODS: The MAF, a newly developed high-resolution
      detector with very low instrumentation noise and large variable gain, was used
      for the study. It has 35-micron pixels and a 500-micron thick CsI HR-type
      phosphor. The detector MTF was measured using the slanted edge method and the
      focal spot MTF's were measured using a standard pin-hole assembly. For the
      comparison analysis, the GMTF and GDQE were determined for three different focal
      spots (0.3 mm, 0.5 mm and, 0.8 mm) with a magnification factor of 1.25. A
      stainless- steel stent was also imaged with the same magnification for all three
      focal spots. RESULTS: The MAF's performance is affected significantly by the
      choice of focal-spot size because of its very high resolution. The GMTF and GDQE
      comparison for three focal spots showed significant degradation, increasing from
      small to large focal spot. The GMTF values were found to be 0.09, 0.05 and 0.01
      at 5 cycles/mm for the small, medium and large focal spot, respectively. The
      corresponding values for GDQE were 0.1, 0.03 and 0.001. These results
      demonstrating the effect of choice of focal spot on the image quality are
      supported by line profiles obtained across the stent images. CONCLUSIONS: The
      results of this study demonstrate the significance of focal-spot size on system
      performance when using a high-resolution detector with a realistic magnification
      and shows the importance of choosing the minimum focal-spot size. (Support: NIH
      Grant R01EB002873) NIH Grants R01-EB008425, R01-EB002873 and an equipment grant
      from Toshiba Medical Systems Corp.

PMID- 28519500
TI  - SU-E-I-38: Optimizing CT Slice Width Measurements.
AB  - PURPOSE: For almost four decades bead and wire ramps have been used in the
      evaluation of slice width as part of QA testing for CT scanners. While each of
      these approaches have been recognized and accepted as reliable, in this paper we
      investigate the differences, advantages and limitations of these tools. Moreover,
      we study the effect of varying the field of view (FOV) and focal spot size.
      METHODS: The Catphan(r) 700 phantom includes two pairs of bead ramps (coarse and
      fine) and a pair of wire ramps in the same module providing an ideal setting for
      comparing bead ramps and wire ramps. The phantom was scanned using three devices
      from two different manufacturers. The data set consisted of 428 slices of
      0.5,1,2,4,8 and 10 mm thickness. For the study of FOV and focal spot, 512 slices
      from the Catphan(r) 600 were acquired. All images were analyzed using Image Owl
      Catphan(r) QA software. RESULTS: For 0.5mm slices, bead ramps gave more accurate
      and precise (lower variance) estimation of the thickness than wire ramps. For 2-4
      mm slices, the two approaches performed on equal terms while for the thickest
      slices (8 and 10mm), the wires gave more precise results. For thin slices, a
      small FOV (100mm) gave better results and lower spread than a large FOV (240mm).
      Finally, a small focal spot gave significantly better results than a large one
      using wire ramps for 0.5 and 1mm slices. CONCLUSIONS: For measuring thin slices,
      the use of bead ramps, with adequately small FOV and a small focal spot should be
      advised. For measuring thick slices, wire ramps will give less variability
      although bead ramps give equally accurate results on average. Funding provided by
      The Phantom Laboratory, Incorporated and Image Owl, Incorporated.

PMID- 28519501
TI  - SU-E-I-10: Putting Teeth into Your CT Dosimetry Program: Approaches to Cone- Beam
      Dental/Maxillofacial CT Dosimetry.
AB  - PURPOSE: To review and compare different approaches to the problem of dosimetry
      for limited field-of-view (FOV) cone beam CT devices for dental and maxillofacial
      applications. METHODS: The determination of patient doses from specialized, cone
      beam CT devices for dental and maxillofacial work requires medical physicists to
      re-evaluate their dosimetry methods. These devices work in cone-beam geometry,
      with an axial field dimension on the order of the lengths of the standard head
      CTDI phantom and pencil ionization chamber. They may also utilize less than 360
      degree scans, resulting in asymmetrical radiation distributions. This operating
      regime is far from that for which conventional CT dosimetry was designed, and
      alternative approaches must be considered. The alternatives include extensions of
      conventional CT dosimetry currently used for large axial FOV scanners (e.g. the
      extended CTDI parameter (CTDIe) for the Toshiba Aquillion One with 160 mm axial
      FOV) and the new method based on point dosimetry measurements recently formalized
      in AAPM Report TG-111. Conventional, modified-conventional, and TG-111 dosimetry
      measurements are used in two CT dose phantoms (adult head and pediatric head) to
      obtain dose indices for the Planmeca ProMax 3D Max dental CT scanner. Surface
      dose maps are generated using radiochromic film for correlation with the chamber
      dosimetry. RESULTS: Results for the three dosimetry approaches are compared for
      the specific case of the ProMax 3D Max scanner. Strengths and weaknesses of the
      three measurement paradigms for this type of application are compared.
      CONCLUSIONS: The increasing availability of specialized scanners operating in
      full cone-beam mode will require the clinical medical physicist to be conversant
      with extensions to the CT dose index methodology suitable for this equipment.

PMID- 28519502
TI  - SU-E-I-48: Comparison of CTDIw and Averaged CTDI Over X-Y Plane.
AB  - PURPOSE: The goal of this study is to investigate the accuracy of using CTDIw to
      estimate the averaged CTDI over x-y plane. METHODS: We used a Siemens Sensation
      16 slice scanner, a nested 3 piece CTDI phantom with diameters of 10, 16, and 32
      cm for each piece, a CT pencil ion chamber, and aluminum oxide OSL dosimeters. In
      axial mode, we measured the exposure with ion chamber at the 3, 6, 9, and 12
      o'clock positions at distances of 4, 7, and 15 cm from the center of a 32 cm CTDI
      phantom, as well as at the center of the phantom. Measurements were performed at
      80, 100, 120, and 140 kVp on the adult abdomen, adult head, and pediatric body
      phantom, using only the distances of 0, 4, and 7 cm from the phantom center for
      the smaller 16 cm diameter phantom. We did similar measurements using nanoDot
      dosimeters and the 32 cm phantom at 120 kVp in helical mode using a pitch of 0.8,
      1.0, and 1.2. RESULTS: The data obtained at four different outer clock positions
      was averaged and three models (linear, quadratic, and exponential) were used to
      fit exposure as a function of distance to the phantom center. We calculated the
      average CTDI over the x- y plane mathematically using the above models and
      compared the results with traditional CTDIw. In axial mode, the difference is
      within 6% for 32 cm phantom, with a slight increase in variance at low kVp, while
      the difference is within 1% for the 16 cm phantom. In helical mode with OSLs, the
      difference is within 2.5% for pitch 0.8-1.2. CONCLUSIONS: The current CTDIw
      provides an accurate estimate of the averaged CTDI over the x-y plane for both
      axial and helical modes.

PMID- 28519503
TI  - SU-E-I-20: The Application of Traditional Snake Model and Balloon-Snake Model in
      Automatic Organ Contouring.
AB  - PURPOSE: To compare the traditional Snake model and Balloon-Snake model on
      automatic organ contouring. METHODS: For tumors in brain, chest and abdomen, two
      patients were enrolled for each part. Grey matter, lung and liver for each
      patient were contoured automatically by Snake model and Balloon-Snake model, and
      were also contoured manually by radiologist respectively. Characteristics and
      dynamic capabilities were compared between the two models. RESULTS: The
      traditional Snake model will bring good contouring Result only if the primary
      contour is close enough to the target edge. But, if the force field area is
      relatively small, the automatic contouring will not bring good Result on boundary
      deep concave. The Balloon-Snake model can overcome those shortcomings and improve
      the traditional Snake model. However, the primary model of Balloon-Snake can not
      cross border, doesn't work well on boundary cracks reconstruction, has small
      force field. CONCLUSIONS: The Balloon-Snake model improved the traditional Snake
      model and has better dynamic capabilities. It has also more practical value on
      automatic organ contouring.

PMID- 28519504
TI  - SU-E-I-31: Evaluating Brain Imaging Material (BIM) as a Brain Tissue Surrogate
      for Use in Neuro-Endovascular Imaged Guided Intervention (EIGI) Research.
AB  - PURPOSE: A brain tissue surrogate material was needed to fill the anatomical
      cavity of a skull to create a phantom for use in simulated Neuro-EIGI procedures.
      To enable diagnostic and interventional procedure simulation, the BIM must fit
      into and be congruous with the interior surface of the skull, be reusable, and
      allow the implantation of vascular phantoms. The material must reasonably
      reproduce the automatic technique parameter selections observed during Neuro-EIGI
      procedures. METHODS: We formulated a putty- like material to be used as the BIM.
      Its x-ray attenuation properties were evaluated by comparison of the fluoroscopic
      and radiographic technique parameters automatically selected for a BIM-filled
      skull on a Toshiba Infinix angiographic C-arm unit to those of a solid
      anthropomorphic head phantom at various projection angles. The same comparison
      was made between the skull phantom without BIM in the cavity and the
      anthropomorphic head phantom. The BIM linear attenuation coefficient was
      calculated and compared to that of PMMA, a common tissue analog plastic. RESULTS:
      The BIM keeps its shape, is moldable and reusable, and is congruent to the
      skull's interior surfaces. It allows for insertion and interchange of various
      custom vascular phantoms at proper anatomic locations. Addition of the BIM to the
      skull cavity improves the matching of the automatically selected parameters to
      those of the anthropomorphic phantom by an average of 96.3% for mAs and by 4.2%
      for kVp in fluoroscopy mode and by 88.6% and 9.0%, respectively, in DSA mode. The
      BIM's experimental and theoretical linear attenuation coefficient for the RQA5
      spectrum differed from PMMA's by about 30%. CONCLUSIONS: Despite the difference
      in attenuation coefficients between the PMMA and BIM, the BIM is a good surrogate
      material for Neuro-EIGI research as shown by its properties of congruity,
      reusability, and device implantation, along with the demonstrated improvement of
      automatically selected technique parameters. Supported in part by: NIH Grants R01
      EB008425, R01-EB002873, and an equipment grant from Toshiba Medical Systems Corp.

PMID- 28519505
TI  - SU-E-I-03: Scatter and Beam Hardening Correction for MUCBCT Scanners Using Monte
      Carlo.
AB  - PURPOSE: Micro CBCT scanners have a broad spectrum of applications in medicine
      and material science. However, CBCT suffers from scatter radiation and spectral
      effects such as beam hardening (BH). In this work an iterative BH- and scatter
      correction algorithm was developed using Monte Carlo (MC) methods. METHODS: Two
      MUCBCT scanner models (XtremeCT and MUCT100 from SCANCO Medical AG) were
      simulated using EGSnrc/EGS++. The scanner measures the attenuation of X-rays
      passing through the phantom and interacting in a scintillating detector. The MC
      method is used to characterize the influence of the scattering and BH- effects.
      In addition, an analytical model is developed in order to correct for the
      scattering effect. For this purpose, by using MC methods, different scatter
      components were analyzed with respect to the number of scatter interactions
      within the given geometry. For the BH-effect, after assessing the detector
      response for an equivalent mono-energetic and scatter-free system using MC
      methods, an analytical correction model was developed. Both correction methods
      were implemented as an iterative reconstruction correction algorithm and were
      tested for various phantoms. RESULTS: MC simulations show that the amounts of
      correction for the scattering and BH- effects are in the same order of magnitude.
      The correction term for scattering effects is a function of the scatter to
      primary ratio only and is mainly due to single scattered particles. The
      contribution of multiple scattered particles to the total scatter signal is small
      and can be approximated by a constant. In all cases tested, the reconstructed
      linear attenuation coefficients converge to the mono-energetic reference values
      after 2-3 iteration steps with a deviation of about 1%. CONCLUSIONS: By using an
      iterative correction algorithm using single scatter approximation, BH- and
      scatter correction can be performed accurately for MUCBCT scanners. This work was
      supported by CTI-10629.1 and SCANCO Medical AG.

PMID- 28519506
TI  - SU-E-I-42: Measurement of X-Ray Beam Width and Geometric Efficiency in MDCT Using
      Radiochromic Films.
AB  - PURPOSE: The purpose of this work was to measure the x-ray beam width and
      geometric efficiency (GE) of a multi detector computed tomography scanner (MDCT)
      for different beam collimations using radiochromic films. In MDCT, the primary
      beam width extends the nominal beam collimation to irradiate the active detector
      elements uniformly (called 'over-beaming') which contributes to increased
      radiation dose to the patient compared to single detector CT. Therefore, the
      precise determination of the primary beam width and GE is of value for any CT
      dose calculation using Monte Carlo or analytical methods. METHODS: Single axial
      dose profiles free in air were measured for 6 different beam collimations nT for
      a Siemens SOMATOM Sensation 64 Scanner with Gafchromic XR-QA2 films. The films
      were calibrated relative to the measured charge of a PTW semiflex ionization
      chamber (type: 31010) for a single rotation in the CT scanner at the largest
      available beam collimation of 28.8 mm. The beam energy for all measurements in
      this work was set to 120 kVp. For every measured dose profile and beam
      collimation the GEin-air and the full-width-at-half- maximum value (FWHM) as a
      value for the x-ray beam width was determined. Over-beaming factors FWHM / nT
      were calculated accordingly. RESULTS: For MDCT beam collimations from 7.2 (12*0.6
      mm) to 28.8 (24*1.2 mm) the geometric efficiency was between 58 and 85 %. The
      over- beaming factor ranged from 1.43 to 1.11. For beam collimations of 1*5 mm
      and 1*10 mm the GE was 77 % and 84 % respectively. The over-beaming factors were
      close to 1, as expected. CONCLUSIONS: This work has shown that radiochromic films
      can be used for accurate x-ray beam width and geometric efficiency measurements
      due to their high spatial resolution. The measured free-in-air geometric
      efficiency and the over-beaming factor depend strongly on beam collimation.

PMID- 28519507
TI  - SU-E-I-14: Evaluation of Image Quality Parameters of Small and Full Field of View
      Cone Beam Computed Tomography Dental Imaging Systems.
AB  - PURPOSE: CBCT systems are being used in dental preoperative planning, which rely
      on 3D surface model representations of the jaw, using a segmentation algorithm
      for extracting the bony tissues. However, CBCT systems have differences of
      imaging parameters, which affect the image quality and segmentation process,
      influencing the accuracy of the 3D surface models used in preoperative implant
      planning. The purpose of this study was to evaluate image quality parameters of
      different types of CBCT systems, showing their potentialities and limitations for
      preoperative planning. METHODS: Images were acquired using the systems: i-CAT
      (Imaging Sciences International Inc., USA); ProMax 3Ds (Planmeca Oy, Finland);
      Kodak 9500 Cone Beam 3D and Kodak 9000C Cone Beam 3D (Kodak Dental Systems, USA).
      CBCT systems were divided into categories, related to their field of view size:
      Small Field of View (SFOV) and Full Field of View (FFOV) systems. Image quality
      parameters evaluated were: CT number accuracy, uniformity, noise level, and
      artifacts. Measurements were performed in slices around the center of the
      phantom. RESULTS: CT numbers are highly affected by the amount of mass outside
      the reconstructed volume, confirming the relation between density variability and
      imaging volume. The mean CT number shows little correspondence to that of the
      traditional CT protocols. The variability is especially high in the case for SFOV
      systems. Uniformity artifacts occur at the top or bottom of the FOV, and Result
      in voxel values that are unsuitable for CT number accuracy analysis. SFOV systems
      showed a higher noise level (11,9%) comparing to FFOV systems (4.4%). CONCLUSION:
      The experiments showed that the size and position of the FOV affect the image
      quality for all CBCT systems. The study was limited to the CBCT systems that were
      accessible when this study was conducted. Whether new CBCT systems models would
      perform differently remains to be investigated.

PMID- 28519508
TI  - SU-E-I-52: Noise Level and Contrast Dependent Behavior of MTF in Iterative
      Reconstruction CT Imaging.
AB  - PURPOSE: Iterative reconstruction (IR) technique is growingly used in clinical CT
      imaging due to its ability to provide improved image quality at lower patient
      doses. However, the nonlinear frequency response of IR technique, which may
      affect quantitative analysis, is rarely explored. This study evaluates noise
      level and contrast dependent behavior of MTF in IR CT imaging with a multi
      contrast slit phantom scanned at different dose levels. METHODS: A multi-contrast
      slit phantom was created consisting of acrylic panel and aluminum foils of
      different thickness. Images were acquired on multi-detector CT (Discovery CT750
      HD: GE) at two dose levels (10mAs and 200mAs), and were reconstructed using FBP
      and two IR technique (ASIR50 and VEO). Line spread functions were extracted
      across slits of two different thickness (80um and 144um) on images scanned at two
      dose levels, and were Fourier transformed to evaluate the MTFs of IR and FBP
      reconstruction techniques, producing a total of 12 MTF curves. RESULTS: MTF of
      200mAs scan showed clearly higher responses up to 28% than that of 100mAs scan in
      VEO, marginally higher values up to 5% in ASIR50, and were in good agreement in
      FBP. At same dose level, the MTFs with higher contrast slit (144um) showed
      marginally higher response than that of lower contrast slit (80um) in VEO and
      ASIR50. CONCLUSIONS: Our study revealed that MTF of IR technique degrades
      depending on noise level at low dose scan. Therefore, we recommend that its
      characteristic should be considered in quantitative analysis such as lesion size
      measurement.

PMID- 28519509
TI  - SU-E-I-24: Determining the Optimal B-Values to Use in Diffusion Weighted Imaging
      for Differentiating Benign and Malignant Breast Lesions.
AB  - PURPOSE: To investigate and determine the optimal b-values for Diffusion Weighted
      Imaging(DWI) for Apparent Diffusion Coefficient(ADC) maps in differentiating
      normal, benign and malignant breast tissue. METHODS: Twenty-five patients
      underwent diffusion-weighted magnetic resonance imaging (DWI-MRI) and
      conventional breast MRI with suspicious breast fmdings(BIRADS >4). Breast lesions
      were defined by pathology. The DWI was acquired with different b-values ranging
      from 0,500, 600,750 and 1000s/mm2 . Apparent Diffusion Coefficient(ADC) maps of
      breast tissue were constructed using different b-values, e.g., using either 2 b
      values(0- 1000) or combinations of 3 or more (0,500,1000 or 0,600,750,1000).
      Quantitative analyses of the ADC maps of glandular, fatty and lesion tissue were
      obtained. Ratios of lesion to glandular tissue(L/GT) and signal to noise(SNR)
      were assessed. Paired t-tests were performed for statistical significance.
      RESULTS: Eighteen patients had invasive ductal carcinoma and 7 had benign breast
      lesions. The mean ADC value for malignant lesions using all b values was 1.17+/
      0.16*10-3mm2 /s with a lesion to glandular(L/GT) ratio=0.65. The benign lesions,
      ADC map value was 1.86+/-0.03*10-3mm2 /s with L/GT=0.98. There was a significant
      difference(P<0.05) between benign and malignant lesions ADC map value.The lowest
      SNR(12+/-6) was with single b-values. There was a significant difference(P<0.05)
      in SNR with multiple b-values(34+/-6) compared to single b-values. The highest
      SNR was given by using two b values greater than 500. Finally, the background
      noise for all combinations was surprising stable and ranged between 60+/-20%.
      CONCLUSIONS: This is the first study to investigate the effect of changing
      different b values in DWI breast imaging. There were significant differences in
      the SNR between single and multiple b values. Our data show suggest that the
      recommended b-values for DWI in breast are 0, and two that are 500 or greater.
      Therefore use of at least 3 b-values in DWI/ADC mapping of breast lesions are
      needed for better characterization of benign and malignant breast tissue.
      P50CA88843, Avon Foundation for Women:01-2008-012, U01CA070095, andU01CA140204.

PMID- 28519510
TI  - SU-E-I-16: Automated Liver Segmentation Method for CBCT Dataset by Probabilistic
      Atlas Construction.
AB  - PURPOSE: The aiming is getting accurate liver contour structures automatically
      for following adaptive radiation therapy in daily CBCT images which is very low
      contrast comparing the planning CT. METHODS: Probabilistic atlas is constructed
      by 50 intravenous contrast planning CT images by iterative affine registration
      process. The incoming CBCT images are registered with the atlas using deformable
      registration algorithm which is based on edge preserving scale space, and the
      liver contour structures are generated automatically by using the deformation
      map. Incorporating the intensity distribution of candidate liver region into the
      segmentation processing, we can further remove the irrelative tissue from the
      original liver region. Our algorithm is capable of segmenting the liver from low
      contrast cone beam CT images. In our probabilistic atlas construction process,
      firstly one training data is arbitrarily chosen as reference image while the rest
      of training datasets are registered to this reference using the affine
      transformation. For improving the efficiency of our method, iterative
      construction method is employed. The resulting atlas which is gained before is
      used as the reference image for the following atlas construction. This process
      can be iterated by many loops. However, we used two iterations for efficiency.
      This iterative atlas construction process can avoid bias toward the specific
      patient. RESULTS: The experiments are tested on 10 newly incoming patient data.
      The volumetric overlap is on an average 87%-94% comparing with manually segmented
      tumors by oncologists. After evaluation by clinical oncologists, they concluded
      that the segmentation results are close to the manual results and the liver
      contours on CBCT which is produced by the deformation field automatically can be
      used for following adaptive radiation therapy. CONCLUSIONS: We can conclude that
      the proposed segmentation method is very effective with low contrast CBCT for
      adaptive radiation therapy in daily using.

PMID- 28519511
TI  - SU-E-I-54: Evaluation of High Contrast Resolution for Model Based Iterative
      Reconstruction of Sinus Examinations.
AB  - PURPOSE: To evaluate high contrast resolution of Model Based Iterative
      Reconstruction used with typical sinus examination acquisition parameters.
      METHODS: MBIR has recently become available as a recon option on a clinical
      scanner (Discovery HD750, GE Healthcare). In this work, we evaluate high contrast
      resolution for scan and reconstruction options that are available for sinus
      examinations. For this study we used our adult sinus CT protocol reconstructed
      with filtered back projection, and two alternative scans reconstructed with IR.
      Our conventional adult sinus CT protocol utilizes a high resolution scan mode
      which is not compatible with the scanner's IR recon option. The two additional
      scans are with high resolution option off, one with the head SFOV, and one with
      the body SFOV. Using IR and the head SFOV, reconstructed images have a 1024 *
      1024 pixel matrix. Using IR and the body SFOV, reconstructed images have a 512 *
      512 pixel matrix. Three evaluations of high contrast resolution are made for
      these images. A wire phantom is scanned for assessment of image modulation
      transfer function. The bar patterns of the ACR phantom are visually assessed for
      quality in both axial and coronal reformats. RESULTS: MTF curves show 50% values
      of 6.8, 7.5, and 7.7 lp/cm for Body IR 512 * 512, Head IR 1024 * 1024, and
      filtered back projection with HD Bone kernel. The 10% MFT curves for these
      reconstructions are 11.2, 11.9, and 12.1 lp/cm. Visual evaluation of the ACR
      phantom at 15 cm display field of view demonstrates resolution of the 10 lp/cm
      bar patterns for all reconstructions with better visualization of the axial
      versus coronal recons. CONCLUSIONS: MBIR reconstruction demonstrates high
      contrast resolution that is comparable with our conventional sinus examination.

PMID- 28519512
TI  - SU-E-I-26: Estimation of Micro-Angiographic Fluoroscope (MAF) Gain Settings for
      Digital Subtraction Angiography (DSA) Based on the Fluoroscopic Exposure.
AB  - PURPOSE: The MAF is a new high-resolution detector which is being clinically
      evaluated in neuro-vascular procedures. The detector contains a large-dynamic
      range, high-sensitivity light image intensifier with variable gain. Since the MAF
      is a research prototype only partially integrated with the clinical system, x-ray
      technique parameters must be set manually. To improve workflow we developed an
      automatic method to estimate and set the proper LII voltage (MAF gain) for DSA
      acquisition based on the fluoroscopic parameters. METHODS: The detector entrance
      exposure (XD) can be written as the x-ray tube output exposure (Xo) times an
      object attenuation factor and an inverse-square correction. If the object
      attenuation, scatter and distances are unchanged and the effect of x-ray kVp
      changes are neglected, then the DSA XD can be expressed as the ratio of
      Xo(DSA)/Xo(Fluoroscopy) multiplied with XD(fluoroscopy). We measured Xo for
      fluoroscopy and DSA for mAs and kVp ranges appropriate to neuro- vascular
      interventions and fit the data with a 2D function. To estimate the
      XD(Fluoroscopy) we derived a curve of XD versus LII-voltage for a mid- dynamic
      range average pixel gray-level. Since the MAF system during clinical fluoroscopy
      automatically adjusts the LII voltage until the desired gray-level value is
      achieved, by reading that voltage we can estimate the XD(Fluoroscopy). Using the
      2D-fit function, Xo(DSA) is automatically calculated for the kVp and mA values
      set and XD(DSA) can be estimated using the relation above. Using the inverse LII
      calibration curve, the proper LII-voltage can be determined for the desired
      average gray-level. RESULTS: The algorithm was implemented and evaluated in
      thirty-two in-vivo DSA runs on rabbits. The proper LII voltage was selected in
      all cases with no failures. CONCLUSIONS: Using the fluoroscopic LII gain setting
      to determine the appropriate DSA setting can greatly improve the workflow in
      clinical evaluations of the MAF. NIH Grants R01-EB008425, R01-EB002873 and an
      equipment grant from Toshiba Medical Systems Corp.

PMID- 28519514
TI  - SU-E-I-09: Patient Organ Doses from KV-CBCT Acquisitions as Function of Patient
      Size and Scan Protocols.
AB  - PURPOSE: To investigate the organ dose dependence on patient size and position
      resulting from an image guidance procedures. Depending upon the degree of
      variability between patients, the feasibility tabulating the organ dose based
      upon patient size and imaging acquisition procedure. Such tables could be useful
      in estimating and accounting for organ dose resulting from imaging procedures.
      METHODS: Monte-Carlo methods were used to calculate radiation dose to the patient
      resulting from a kV CBCT imaging scan based upon CT image data. A Python program
      was created to generate DVHs using the calculated 3D dose matrix and the DICOM-RT
      Structure Set for the patient. A number of head and pelvic CT scans were used in
      the study, and the resulting DVHs were analyzed to determine the variation of
      organ dose as a function of patient size. RESULTS: For the head scans in supine
      position, the average of the mean doses for some organs, along with the standard
      deviation in those mean doses, are as follows:Brainstem: 0.25cGy +/-
      0.02cGyBrain: 0.26cGy +/- 0.01cGyOptic Chiasm: 0.22 +/- 0.03cGyBone: 0.55 +/-
      0.04cGyAnterior Skin: 0.13 +/- 0.05cGyPosterior Skin: 0.23 +/- 0.06cGyEye:
      0.11cGy +/- 0.05cGyFor Pelvic scans, dose to organs such as rectum, have likewise
      been shown to have some variation between patients of different sizes.
      CONCLUSIONS: The results show that it is possible to express organ dose as a
      function of imaging procedure, imaging device, scan location, body size, and
      orientation. For example, using a standard head scan on an OBI 1.4 system, the
      dose to the eye ranged from 0.05-0.20cGy, depending upon the patient size.
      Considering the amount of imaging dose compared to the therapeutic dose, this
      study indicates that organ dose could be estimated by using tabulated values
      based upon the scan procedure and patient size.

PMID- 28519513
TI  - SU-E-I-37: A Renewed Look at CT Numbers as Encountered in the Diagnostic and
      Therapeutic Range.
AB  - PURPOSE: With the development of RT treatment planning systems that use the
      relationship between CT number and Electron Density (ED), rather than the Linear
      Attenuation Coefficient (LAC) of a given material, a number of authors have
      pointed out the divergence between the linearity of CT numbers vs. LAC in the
      diagnostic range compared to the relationship between the CT number and ED. This
      paper will review the differences and similarities, and describe a new set of
      phantom test objects and automated software that can be used to automatically
      assess both scales. In particular the relative importance of atomic number (Z)
      and the relative impact of Coherent vs. Incoherent effects at high Z levels will
      be evaluated. METHODS: A newly developed phantom (Catphan(r) 700) has an expanded
      set of sensitometric samples of known density, electron density, and chemical
      composition (Z effective). CT scans of the phantom were obtained at various
      energies (kVp) and the measured CT numbers were compared to the known physical
      characteristics mentioned above. Regressions between measured CT numbers, linear
      attenuation coefficients (with and without coherent scattering effects), and
      electron density for the materials were performed. Effects of different materials
      and the inclusion of coherent scattering on linearity scale and effective energy
      were established. RESULTS: The linearity scale and effective energy are shown to
      be dependent on the selection of materials scanned and the inclusion/exclusion of
      coherent scattering effects in the linear attenuation coefficients. Electron
      density deviates significantly from a linear relationship with CT number.
      CONCLUSIONS: Caveats accompanying high Z materials are reinforced regarding
      application to the RT relationship between CT number and electron density.
      Interesting results were obtained for the influence of coherent vs. incoherent
      scattering, which appears to be important as the number of slices and scanning
      volume increases in CT. Funding provided by The Phantom Laboratory, Incorporated
      and Image Owl, Incorporated.

PMID- 28519515
TI  - SU-E-I-47: Comparison of Risks for Two Medical Imaging Procedures.
AB  - PURPOSE: Radiologists may need to decide which type of image procedure is most
      appropriate for a particular patient. One factor relevant in making this decision
      is the relative risk of secondary cancers due to each relevant procedure.
      Differences in the risk posed by each method are not just due to the total
      radiation dose imparted by each procedure, but also the distribution of absorbed
      dose across various organs in the imaging procedure. Two imaging procedures with
      the same total radiation dose may pose different risks of differential
      sensitivity to radiation across organs. METHODS: New methods of radiation
      dosimetry enable us to estimate the dose distribution across organs in individual
      patients. We propose a measure of the relative risk of two medical imaging
      procedures derived from the hazard function of cancer incidence. The relative
      risk measure is shown to approximately equal to a weighted sum of the dose
      difference in each organ. The weights are proportional to organ specific
      incidence rates. The measure is also sensitive to factors such as the patient's
      age at exposure to radiation, the attained age and gender, as well as the
      incidence characteristics of the population to which the patient belongs. We
      propose to quantify the effects of these factors using information from
      publically available SEER database for US based patients as well as the LSS study
      of atomic bomb survivors. The method is illustrated by application to a study
      comparing chest and abdominal CT scans for a group of pediatric patients.
      RESULTS: Fig. 1 shows higher absolute relative risk for those exposed at younger
      ages, with chest scans being riskier for females while abdominal scans were
      riskier for males. At higher ages, the relative risk is approximately equal.
      CONCLUSIONS: Relative risks can quantify risks comparisons between imaging
      procedures.

PMID- 28519516
TI  - SU-E-I-19: Local Search Clustering Algorithm for DCE-MRI Analysis.
AB  - PURPOSE: To develop a local search clustering algorithm for analyzing the dynamic
      contrasted enhanced (DCE)-MRI data for determining the vascular permeability. The
      clustered signal will have better contrast-to-noise ratio (CNR) and thus can
      improve the analysis. METHODS: In DCE-MRI, data often suffer from low CNR. The
      CNR is particularly poor in central nervous system and could lead to spurious
      results. We propose a local search clustering algorithm that groups proximal
      voxels with similar uptake curves and T1 values. The algorithm starts with a seed
      voxel, and then grows outward to recruit new voxels into a cluster. Once a
      cluster is formed, all members of the current cluster form a 'seed collection'
      and the seed point of the cluster becomes the seed collection. The expansions and
      updates continue with the seed point/collection until the stopping criterion is
      met. To investigate the effectiveness of our clustering algorithm, we used a
      64*64 2D Shepp-Logan phantom. Variations on the T1 values and permeability
      parameters were applied on different regions in the phantom. The time resolution
      was set to 30sec and 82 post-contrast data were created. After the DCE-MRI data
      were generated, Gaussian noise was applied to the images to investigate the
      effect of noise on the clustering algorithm. DCE analysis was performed on the
      clustered data and the results were compared against the Result obtained from
      voxel-by-voxel analysis. RESULTS: The addition of noise degraded the results of
      DCE estimation. The clustering algorithm on average reduced the errors of the
      permeability parameters by more than 50% compared to the voxel-by-voxel analysis.
      CONCLUSIONS: We developed a local search clustering algorithm to segment the
      concentration time curves of the DCE-MRI data. The proposed clustering algorithm
      enhances the apparent CNR within the clustered data and reduces the errors of the
      permeability parameters.

PMID- 28519517
TI  - SU-E-I-58: Objective Models of Breast Shape Undergoing Mammography and
      Tomosynthesis Using Principal Component Analysis.
AB  - PURPOSE: To develop an objective model of the shape of the compressed breast
      undergoing mammographic or tomosynthesis acquisition. METHODS: Automated
      thresholding and edge detection was performed on 984 anonymized digital
      mammograms (492 craniocaudal (CC) view mammograms and 492 medial lateral oblique
      (MLO) view mammograms), to extract the edge of each breast. Principal Component
      Analysis (PCA) was performed on these edge vectors to identify a limited set of
      parameters and eigenvectors that. These parameters and eigenvectors comprise a
      model that can be used to describe the breast shapes present in acquired
      mammograms and to generate realistic models of breasts undergoing acquisition.
      Sample breast shapes were then generated from this model and evaluated. The
      mammograms in the database were previously acquired for a separate study and
      authorized for use in further research. RESULTS: The PCA successfully identified
      two principal components and their corresponding eigenvectors, forming the basis
      for the breast shape model. The simulated breast shapes generated from the model
      are reasonable approximations of clinically acquired mammograms. CONCLUSIONS:
      Using PCA, we have obtained models of the compressed breast undergoing
      mammographic or tomosynthesis acquisition based on objective analysis of a large
      image database. Up to now, the breast in the CC view has been approximated as a
      semi-circular tube, while there has been no objectively-obtained model for the
      MLO view breast shape. Such models can be used for various breast imaging
      research applications, such as x-ray scatter estimation and correction, dosimetry
      estimates, and computer-aided detection and diagnosis.

PMID- 28519518
TI  - SU-E-I-30: Impact of Physician Practice on Patient Radiation Dose during CT
      Guided Biopsy Procedures.
AB  - PURPOSE: The major concern with CT fluoroscopy is patient radiation dose, which
      is determined by applied technical parameters as well as practitioner/operator
      practice, e.g. habits and choice of dose saving features. This study is to
      investigate the effects of these intangible factors on patient doses. METHODS:
      381 patients underwent CT biopsy were retrospectively studied. Patient doses
      (dose length product, DLP) were analyzed and compared. Comparisons were made
      among physicians using only conventional intermittent shots, physicians using a
      low mA dose saving feature, and physicians using a combination of both. Linear
      regression analyses were performed to investigate any possible relationship
      between the variables and the patient dose. The Patient detriment index (PDI) was
      developed to set a threshold for the purpose of the Joint Commission sentinel
      dose events monitoring. An odds ratio was calculated to determine the odds of a
      group of patients receiving a dose above the median threshold when compared to
      another group. RESULTS: The median DLP for all physicians was 1194 mGy-cm. There
      is a significant difference (p<0.01) between the doses patients received
      (DLP=539.8 +/-76 mGy-cm) when physicians used dose saving feature vs. when the
      feature was not used (DLP=1269.7+/-659 mGy-cm). In general, those physicians who
      used dose saving feature have a lower relative PDI (<1) compared to the PDIs (>1)
      without dose feature. This is not absolute since some physicians who did not use
      the dose saving feature have PDIs<l. An odds ratio estimate of 7.7 with a 95%
      confidence interval of 3.27 to 18.1 indicates that patient radiation dose
      strongly depends on the practitioner. CONCLUSIONS: Adjustments of practice
      habits, the use of CT dose saving features or both may be needed to improve
      patient care for CT fluoroscopy.

PMID- 28519519
TI  - SU-E-I-02: Size-Dependent Computed Tomography Histogram Analysis: Towards Breast
      Tissue Segmentation.
AB  - PURPOSE: To examine the effects of object size on scatter-corrected CT histograms
      to be used in threshold-based tissue segmentation. METHODS: A polyethylene cone
      filled with various concentrations of water and methanol mixtures, simulating
      glandular and adipose tissues, were imaged with our quasi-monochromatic dedicated
      breast CT, and scatter corrected using beam-stop array measurements. Images were
      reconstructed using iterative OSC, and individual coronal slices along the
      central axis of the cone were analyzed, with radii ranging from 3.25-6.25cm.
      Histograms from each slice were fit with two Gaussians (fluid filling and cone
      material) using nonlinear least squares methods, and the corresponding standard
      deviation and peak centroid of each filled material were evaluated as a function
      of object radius. Identical methods were applied to dedicated breast CT images of
      four patients for clinical comparison. RESULTS: Analysis of phantoms and breast
      data indicates low correlation between the standard deviation and object
      diameter. The centroids of the Gaussian peaks demonstrate an inverse linear
      relationship with increasing object size, independent of object material. The
      clinical datasets show a similar linear relationship between centroids and breast
      radius. CONCLUSIONS: Data indicate that using a linear combination of Gaussian
      distribution functions to segment breast tissue in scatter corrected, quasi
      monochromatic cone beam dedicated breast CT is possible. An object size
      independent variation of attenuation values may allow for consistent restraints
      on initial fit parameters, resulting in improved confidence using Gaussian curve
      fitting. Appropriate scaling of the size-dependent volume slices, or independent
      slice analysis, is necessary to minimize binning variability for accurate tissue
      segmentation using Gaussian curve fitting. This work is supported by National
      Institutes of Health (R01-CA096821) and NIH Training Grant (T32-EB007185). MPT is
      the inventor of this hybrid breast imaging technology, and is named as an
      inventor on the patent for this technology assigned to Duke (US Pat. #7,609,808).
      If this technology becomes commercially successful, MPT and Duke could benefit
      financially.

PMID- 28519520
TI  - SU-E-I-41: Characterization of a Linear Fiber-Optic Coupled Dosimeter.
AB  - PURPOSE: This study investigated the dosimetry performance of a linear fiber
      optic coupled dosimeter with a sensitive element varying from 3 to 15 cm in
      length. The dosimeter is comprised of a tissue equivalent plastic scintillating
      fiber coupled to a photomultiplier tube (PMT). The sensitive element has a length
      representative of the dimensions of common adult internal organs and measures the
      absorbed dose along the entire sensitive length. The measurement of absorbed dose
      in one dimensional space provides a more meaningful measure of the average organ
      dose compared to current dosimeters which evaluate the dose at a small volume, or
      point inside the organ. METHOD AND MATERIALS: A fiber-optic coupled dosimetry
      system was modified by increasing the linear dimension of the sensitive element
      to sizes ranging from 3 to 15 cm. A FOC element providing a variable output as a
      function of exposed dosimeter length, beam energy, depth, and beam intensity, was
      characterized for various exposure parameters relating to Computed Tomography. A
      clinical x-ray tube, with half-value layer of 5.60 mm Al at 120 kVp, was used to
      evaluate the dosimeter response to beam energy, intensity, beam quality, and
      exposed length. RESULTS: The system consistently demonstrated linearity with tube
      output and length of the sensitive element and offering excellent sensitivity and
      reproducibility. The dosimeter also demonstrated a linear response of detected
      counts to length of scintillation material in the x-ray field over the range of
      interest. The sensitivity with respect to energy and depth showed a positive
      linear dependence. An 8% variation in sensitivity across a 12 cm depth was
      observed within a soft tissue-equivalent medium. CONCLUSION: The system allows
      for rapid and accurate average organ dose measurements relevant to x-ray sources
      within the diagnostic energy range. The response to previously discussed
      parameters was independent of the sensitive element length.

PMID- 28519521
TI  - SU-E-I-13: Evaluation of CT Number with Changing Scan Parameters for Nucletron
      Simulix Evolution CBCT.
AB  - PURPOSE: To quantify the variation in CT number generated by the Simulix
      Evolution CBCT with changes in scan length and phantom thickness. METHODS: Three
      phantoms were used in this study: CIRS Model 610 AAPM CT Phantom, Gammex 467
      Tissue Characterization Phantom, and Catphan 600 phantom. The AAPM Phantom was
      used to assess the variation of HU with phantom thickness. Scans were acquired
      with two field size settings (full- and half-beam) with and without a 3.5 cm
      thick ring. The Catphan and Gammex phantoms were used to assess the Simulix's
      capability of producing a consistent CT-to-ED conversion table with different
      scan lengths, ranging from 1 cm (very thin) to 20 cm (clinical use). The data
      were also compared to data acquired with our in-house CT Sim (GE HiLite
      LightSpeed 16 slice). RESULTS: The AAPM phantom scans with and without the ring
      yielded an average difference in HU of 145 HU (full-beam) and 74 HU (half-beam)
      for each of five inserts. The HU for Cortical Bone (SB3) [largest Gammex electron
      density insert; 1.69] ranged from 923 to 1170 HU for the 4 cm and 1 cm scan
      lengths, respectively. The HU for Teflon [largest Catphan electron density
      insert; 1.867] ranged from 657 to 951 for the 20 cm and 1 cm scan lengths,
      respectively. The HU for air in Catphan ranged from -749 to -905, and the HU for
      LDPE [electron density 0.944] ranged from -82 to -42, for the 20 cm and 1 cm scan
      lengths, respectively. CONCLUSIONS: Results show a large variability in the
      calculated CT number with differences in phantom thickness, as evidenced by the
      results with the AAPM phantom. In addition, there appears to be a dependence on
      scan length, attributed to increased scatter contribution. Further tests will be
      done to evaluate the appropriateness of the use of the Simulix CBCT unit for
      heterogeneity corrected external beam treatment planning. The author has received
      no funding during the course of this research.

PMID- 28519522
TI  - SU-E-I-51: Investigation of Absorbed Dose to the Skin, Eyes and Thyroid of
      Patients during CT Angiography and Comparison with Conventional Angiography.
AB  - PURPOSE: Imaging is one of the most important methods to diagnose cardiovascular
      and especially coronary artery diseases. The advent of multislice CT in recent
      years has made new capabilities for medical imaging. Coronary CT angiography as a
      new imaging method is performed with these devices. Despite of many advantages
      with it, patients absorbed dose is relatively high in coronary ct angiography,
      Then study on various aspects of absorbed dose to patients seems to be necessary.
      The aim of this study was to evaluate absorbed dose to patient's skin, thyroid
      and eye during coronary CT angiography and to compare it with the same organ
      doses in conventional angiography. METHODS: A number of 67 patients referring to
      Isfahan's Azzahra(s) and Sina hospitals for coronary CT angiography imaging were
      investigated to evaluate absorbed dose to their skin, thyroid and eyes. Organs
      absorbed dose was obtained via measurement by TLD. One pair GR-200 type TLDs were
      used for each organ dose measurement. TLDS were calibrated using Co 60 source
      before measuring. Absorbed dose to each organ considered to be as average of TLDs
      readout. Coronary CT angiography was performed either by 64 rows detectors CT
      lighspeed VCT in Azzahra(s) or Philips model in Sina hospitals. RESULTS: The
      average of absorbed dose to skin, thyroid and eye during coronary CT angiography
      was 8.32+/- 1.73, 2.06+/- 1.68 and 0.3+/- 0.16 cGy, respectively. Absorbed dose
      to the same organs during conventional coronary angiography was 6.64+/- 9.30,
      0.15+/- 0.17 and 0.03+/- 0.03 cGy, respectively. There is a significant
      differences in adsorbed dose to these organs between coronary CT angiography and
      conventional angiography(p<0.001).absorbed dose to skin ranges between 5.15-12.22
      cGy for CT angiography and between 0.07-39 cGy in conventional angiography.
      CONCLUSIONS: Absorbed dose to skin is higher than two other organs(thyroid and
      eye) due to direct irradiation. There is a significant variation in absorbed dose
      to skin for both CT and conventional angiography and it is greater for
      conventional angiography. Absorbed dose to organs is higher for CT angiography
      rather than conventional angiography. Radiation absorbed dose depends on various
      imaging selected parameters such as kVp and mAs, then, technicians play an
      important role on it. To decrease adsorbed dose to patients as low as possible
      they must be educated very well and implement what have learned in practice.

PMID- 28519523
TI  - SU-E-I-23: Effective Estimation of Focal Spot Isocenter for Sinograms Obtained
      with Flying Focal Spot Scans for Filtered Back Projection.
AB  - PURPOSE: To validate the determination of parameters required to preprocess
      sinograms obtained by fan beam CT with flying focal spot (FFS) scans, such that a
      combined data set could be used with existing filtered back projection (FBP)
      reconstruction software based on single focal spot (SFS) geometry. METHODS: The
      preprocessing step requires determination of the isocenter for each FFS in the
      target reconstruction geometry. A Philips Brilliance Big Bore CT was used to
      obtain FFS sinograms, which double samples the number of gantry positions
      relative to SFS sinograms, having the same number of detector measurements for
      each gantry position. Mass weighting of sinograms of a Teflon rod scan and curve
      fitting were used to determine isocenters for focal spots. FFS sinograms were
      reformatted before FBP such that each pair of adjacent gantry-step measurements
      were combined by interleaving detector readings. The interleaved measurements
      were assigned to the average gantry angle. Image transition sharpness was
      compared for 33 images of the Teflon rod reconstructed with 1/8 focal spot
      deflection difference to test the isocenter Result. SFS and FFS Sinograms of a
      high- resolution bar pattern phantom were reconstructed by an in-house
      reconstruction code package for resolution comparison. In-house reconstructed
      images of the Teflon rod were compared with scanner images for verifying the
      effectiveness of this sinogram reformatting method. RESULTS: Image profile was
      the sharpest when the Teflon rod sinogram was reconstructed with isocenter
      parameters found by the curve fitting experiment. It was comparable to the
      sharpness of scanner image profile when the in-house image was reconstructed with
      resolution of 1.0mm FWHM. CONCLUSIONS: The good clinical resolution of images
      reconstructed with investigated FFS isocenters suggests that the experiment of
      estimating focal spot centers and reformatting sinograms is effective for
      utilizing reconstruction software that does not support FFS geometry. Supported
      by grant R01 CA149305 and a grant from Varian Medical Systems.

PMID- 28519524
TI  - SU-E-I-34: Air Kerma to Estimated Entrance Skin Dose Look-Up Tables: A Tool to
      Improve Dose Awareness in the Angiography Suite.
AB  - PURPOSE: Although air kerma (AK) is displayed during a case, often it does not
      represent the entrance skin dose (ESD), which can be estimated. The purpose of
      this work is to develop and provide system-customized AK-to- ESD look-up tables
      (LUTs) for immediate reference so that physicians can better evaluate the
      likelihood of deterministic skin reactions to weigh the risk-versus-benefit of
      continuing high-dose procedures. METHODS: Four correction factors are applied to
      estimate ESD from AK: inverse square correction from the interventional reference
      point to the average entrance table position, backscatter factor, mean energy
      absorption coefficient ratio, and measured table attenuation. Correction factors
      are room and service specific; therefore, room-specific AK-to-ESD LUTs are posted
      for easy reference. LUTs also list corresponding tissue reactions and their
      approximate time-of-onset. Protocols can be established for nurse or technology
      staff to provide verbal AK dose notifications during the case at crucial skin
      reaction dose thresholds (e.g. 2Gy indicating possible skin erythema and 5Gy
      indicating potentially prolonged recovery or permanent skin damage). Patient
      follow-up protocols can be established if the estimated ESD exceeds a set trigger
      level (e.g. 5Gy). Staff and physicians surveys evaluate usefulness and impact of
      dose awareness by system users. RESULTS: Two surveys report feedback on LUTs from
      physicians and technologists with 14 years median experience (range: 3-24 years).
      Over three-quarters of all angiography system users identify the LUTs and verbal
      dose notifications as positively affecting the institution's 'Patient First'
      initiative and roughly one-half of the imaging system users indicate that the
      LUTs and site-specific dose trigger level improves the dose awareness of care
      providers. CONCLUSIONS: Our efforts have focused on educating care providers
      about the differences between displayed AK and the estimated ESD. LUTs provide
      physicians and staff an immediate reference for estimated ESD and the associated
      deterministic skin effects at specific dose levels.

PMID- 28519525
TI  - SU-E-I-25: Performance Evaluation of a Proposed CMOS-Based X-Ray Detector Using
      Linear Cascade Model Analysis.
AB  - PURPOSE: The need for high-resolution, dynamic x-ray imaging capability for
      neurovascular applications has put an ever increasing demand on x-ray detector
      technology. Present state-of-the-art detectors such as flat panels have limited
      resolution and noise performance. A linear cascade model analysis was used to
      estimate the theoretical performance for a proposed CMOS-based detector. METHODS:
      The proposed CMOS-based detector was assumed to have a 300-micron thick HL type
      CsI phosphor, 35-micron pixels, a variable gain light image intensifier (LU), and
      400 electron readout noise. The proposed detector has a CMOS sensor coupled to an
      LII which views the output of the CsI phosphor. For the analysis the whole
      imaging chain was divided into individual stages characterized by one of the
      basic processes (stochastic/deterministic blurring, binomial selection, quantum
      gain, additive noise). Standard linear cascade modeling was used for the
      propagation of signal and noise through the stages and an RQA5 spectrum was
      assumed. The gain, blurring or transmission of different stages was either
      measured or taken from manufacturer's specifications. The theoretically
      calculated MTF and DQE for the proposed detector were compared with a high
      resolution, high-sensitive Micro-Angio Fluoroscope (MAF), predecessor of the
      proposed detector. RESULTS: Signal and noise for each of the 19 stages in the
      complete imaging chain were calculated and showed improved performance. For
      example, at 5 cycles/mm the MTF and DQE were 0.08 and 0.28, respectively, for the
      CMOS detector compared to 0.05 and 0.07 for the MAF detector. CONCLUSIONS: The
      proposed detector will have improved MTF and DQE and slimmer physical dimension
      due to the elimination of the large fiber-optic taper used in the MAF. Once
      operational, the proposed CMOS detector will serve as a further improvement over
      standard flat panel detectors compared to the MAF which is already receiving a
      very positive reception by neuro-vascular interventionalists. (Support:NIH-Grant
      R01EB002873) NIH Grants R01- EB008425, R01-EB002873 and an equipment grant from
      Toshiba Medical Systems Corp.

PMID- 28519526
TI  - SU-E-I-36: A Study to Compare Operator Dosimeter Exposure versus Fluoroscopic
      Time and Air Kerma in Fluoroscopically Guided Interventional Procedures.
AB  - PURPOSE: The total effective dose equivalent limit for occupationally radiation
      exposed persons has remained at 50 millisieverts per year since the 1960s. There
      is ongoing discussion whether this limit should be lowered. Whether or not it is
      lowered, all facilities have to adhere to the principle of ALARA (as low as
      reasonably achievable). In a hospital environment, the workers who typically have
      exposures which Result in ALARA investigations having to be performed include
      interventional radiologists, cardiologists, and mobile C-arm operators. At our
      institution there are a limited number of interventional radiologists with one
      person being responsible for performing the majority of the procedures and
      sometimes exceeding the ALARA investigational levels. METHODS: A limited study
      was performed to compare the number, type of studies, cumulative air kerma, and
      fluoroscopic time versus the exposure measured by the personnel dosimeters worn
      by the radiologists. This was also related to the type of angiographic equipment
      in use. RESULTS: The length of fluoroscopic time and cumulative air kerma and
      cumulative DAP appeared to be related to the higher exposures received by the
      operator. The number of procedures performed did not correlate with the personnel
      dosimeter exposure; rather it was the type and complexity of a study and the
      length of fluoroscopic time that was related. CONCLUSION: The number of ALARA
      investigations required has decreased gradually. This could be attributed to
      several factors. These include increased use of available safety items. With an
      increase in the number of interventionalists the work load is distributed more
      equitably. The purchase of new angiographic equipment has resulted in better
      image quality and more shielding options for the operators. The operators are
      periodically reminded to keep fluoroscopic time to a minimum and use appropriate
      settings on the equipment. The equipment is calibrated to provide adequate image
      quality at mid-dose settings.

PMID- 28519527
TI  - SU-E-I-08: KV XVI Cone Beam-CT Dose Measurement Using Gafchromic XRQA2 Film.
AB  - PURPOSE: To study the effect of different filters on the dose response curves of
      the Gafchromic XRQA2 film. To measure the kV XVI cone-beam CT (CBCT) surface dose
      received during 3D and 4D imaging protocols in three body regions (head and neck,
      chest and pelvis). METHODS: GafChromic XR- QA2 film (International Specialty
      Products, Wayne, NJ) dose response curves were generated for three irradiation
      settings: 100 kVp S20/F0; 120 kVp S20/F0 and 120 kVp S20/F1(F1 is a Bowtie
      filter). Film pieces were irradiated in air by the X-ray Volume Imager (XVI)
      mounted on the Elekta Synergy linear accelerator (Elekta, Crawley, UK) and their
      responses were correlated to air kerma measurements. To measure the CBCT surface
      dose, film pieces were taped on the surface of a male Alderson Rando Phantom
      (Alderson Research Laboratories, Inc., Long Island City, New York) at four
      different places (Anterior, Posterior, Right Lateral, Left Lateral). RESULTS: The
      dose response curves of XRQA2 film generated with F1 and F0 filters were found to
      differ by 5 to 7% when the air kerma changed between 2 and 5 cGy. This was less
      than the observed difference (more than 15%, especially at low air kerma) in the
      dose response curves when different energies (100 and 120 kVp) and same filter
      were used. Surface dose ranged between 0.02 cGy and 4.99 cGy. The lowest average
      surface dose (0.05 cGy) was observed when the fast head and neck protocol was
      used, whilst the highest average surface dose (3.06 cGy) was noticed when the
      chest m2 0 protocol was used. CONCLUSIONS: Filters seem to have less effect on
      the dose response of the film compared with energy. Gafchromic XRQA2 film was
      used successfully to measure the XVI CBCT surface dose. The dose was found to
      vary from one imaging protocol to another, with 4D protocols not necessarily
      delivering more doses.

PMID- 28519528
TI  - SU-E-I-46: Quantitative Effects of Clinical Practice on the Efficiency of CT Tube
      Current Modulation for Radiation Dose Reduction.
AB  - PURPOSE: CT tube current modulation (TCM) represents one of the most important
      and efficient methods for radiation dose reduction and has been well accepted.
      However, the possible influence of clinical practice is likely to be ignored
      although venders may provide clinical protocols and instructions. This study is
      designed to further investigate the quantitative effects of clinical operation,
      including radiograph direction and patient positioning, on the efficiency of TCM
      by measuring patient radiation dose and image quality. METHODS: An
      anthromorphologic chest phantom was scanned in a Sensation 40 and a lightSpeed 16
      CT scanner, respectively, using routine chest protocols with TCM. We first
      investigated the effects of radiograph direction. Anterior-posterior (AP),
      lateral, and posterior-anterior (PA) directions were chosen. CTDIvol and dose
      length-product (DLP) were recorded for analyses. Our second experiment studied
      the influence of patient position. First the phantom was positioned at the iso
      center then scanned with AP direction. CTDIvols and DLPs were recorded as
      reference. Then the phantom was moved out of iso-center, up or down 2 and 4 cm
      respectively then scanned. CTDIvols and DLPs were recorded for comparison. For
      each setting, image noise was measured. RESULTS: CTDIvol increases approximately
      20% for PA direction, compared to AP or lateral direction which generates similar
      CTDIvol and DLP with TCM. Image noise for the PA direction is less than those for
      the AP or lateral directions. CTDIvol increases approximately 9% for LightSpeed
      16 and 13% for Sensation 40 when the phantom was moved up 4 cm, while CTDIvol
      decreases approximately 5% for LightSpeed 16 and 8% for Sensation 40 when the
      phantom was moved down 4 cm. CONCLUSIONS: Our quantitative study can direct
      clinical practice to improve the efficiency of CT tube current modulation and
      reduce patient radiation dose.

PMID- 28519529
TI  - SU-E-I-18: Variability of Physiological Parameters Estimated by AATH and MTK
      Models in DCE-MRI.
AB  - PURPOSE: To assess the accuracy and precision of physiological parameters
      estimated by the modified Tofts and Kermode (mTK) model and the adiabatic
      approximation to the tissue homogeneity (AATH) model in dynamic contrast enhanced
      (DCE) MRI. METHODS: Computer simulations were performed using the arterial input
      function (AIF) from Parker et al., and the multiple indicator, multiple path,
      indicator dilution 4 region (MMID4) model for simulating the tissue concentration
      time curve. A set of physiological parameters, simulating a breast tumor, was
      selected as the input to the MMID4. The output was then converted to signal time
      curve using SPGR signal equation. Four levels of Gaussian noise, corresponding to
      SNRs of 100, 50, 20 and 10, were added to the signal time curves, with 1000
      iterations each. These curves were then transferred back to concentration time
      curves on which mTK and AATH models were applied for fitting. For AATH model the
      mean transit time (tau) was held as a fixed parameter ranged from 2 to 10 s, and
      the final solution was selected based on minimizing the root mean square error.
      RESULTS: For common parameters obtained by both models (Ktrans, Ve, Vp), AATH
      provided better accuracy, which agreed with the literatures, whereas mTK resulted
      in superior precision. As expected, greater coefficient of variation (CV) was
      found with smaller SNR in all cases. For the parameters that could only be
      obtained with the AATH model, the CVs were less than 10% for F, E and PS, and
      around 20% for tau, at the SNR level of 20. CONCLUSIONS: Using the MMID4 model
      for data simulation, this work found that AATH model was more accurate but less
      precise for estimating physiological parameters as compared with mTK model. The
      AATH model was able to separate blood flow and permeability estimates with
      reasonable errors and variations.

PMID- 28519530
TI  - SU-E-I-57: CT Dose Metrics: What Are We Tracking.
AB  - PURPOSE: Recent guidance by The Joint Commission and CRCPD recommendations
      require establishing CT reference dose levels (RDLs) for clinical protocols and
      recording CT dose metrics in the patient's medical record. This presentation
      addresses which dose values in the CT report should be recorded for the purposes
      of monitoring patient dose and determining RDLs effectively. METHODS: CT dose
      reports are commonly recorded in the PACS as screen captures, although structured
      reporting is becoming available on current CT scanners and PACS systems. The goal
      is to obtain data that correctly reflects the patient's dose, but the dose
      information captured is not standardized across vendors and can be difficult to
      compare. Multi-phase studies, deviations from established protocols and dynamic
      scanning present problems when recording numbers to establish RDLs because of the
      lack of information on the anatomy scanned. The cumulative DLP and CTDIvol
      manually entered by radiologic technologists into the electronic medical record
      were compared with more detailed dose metrics compiled from PACS images. RESULTS:
      Analysis of this data showed that simple cumulative metrics are a poor indicator
      of patient dose. Major problems are 1) the inclusion of dynamic scan doses
      associated with bolus tracking, which can skew protocol CTDIvol values by a
      factor of up to 20, and 2) add-on scans of non-overlapping anatomy which can
      inaccurately increase apparent patient dose. CONCLUSIONS: Recording CTDIvol to
      monitor patient doses is not straightforward, since details of the actual anatomy
      scanned are lacking without image-based review. More granular dose reporting
      which identifies individual acquisitions is required; however, current RIS
      systems do not provide the flexibility necessary to capture all this information.

PMID- 28519531
TI  - SU-E-I-29: Dose Rate and Image Quality Comparison Between Philips Veradius and GE
      OEC 9900 Elite Fluoroscopic C-Arms.
AB  - PURPOSE: The radiation dose rate and image quality were compared on GE OEC 9900
      Elite Vas 8 and Philips Veradius fluoroscopic C-arms. METHODS: Plastic (PMMA)
      phantoms were used to simulate various thicknesses of soft tissues encountered
      during fluoroscopically-guided interventional procedures while aluminum and
      copper phantoms were used to simulate extremities of different sizes. An image
      quality test tool and an ionization chamber were included in the setup of each
      phantom. The phantoms were imaged in several fluoroscopy modes and at different
      dose levels. The entrance surface air KERMA rate (ESAKR) was measured for each
      phantom in each fluoroscopy mode. Simultaneously, the image quality was assessed
      by counting the number of low-contrast objects visible in the image quality test
      tool. For a given phantom type and thickness, the ESAKR was plotted versus the
      number of visible low-contrast objects to compare the dose rate required for a
      given level of image quality. Additionally, the mean ESAKR per number of objects
      was calculated and p-values were used to test for statistically significant
      differences between the C-arms. RESULTS: For comparable image quality with a
      given phantom type and thickness the ESAKR with the OEC was typically much higher
      than with the Veradius. One-tailed, unpaired t-tests confirm that the mean ESAKR
      per number of visible low-contrast objects was lower for the Veradius than for
      the OEC with all thicknesses of PMMA (p < 0.05). The differences for the aluminum
      and copper phantoms were much smaller and were not statistically significant (p
      values ranged from 0.2 to 0.47). CONCLUSION: In general, the Veradius C-arm
      provided better low-contrast image quality during fluoroscopy, with lower ESAKR
      than the OEC 9900 Elite Vas 8. The differences were statistically significant
      only with PMMA phantoms. Funding support provided by Philips Healthcare (Bothell,
      WA).

PMID- 28519532
TI  - SU-E-l-01: Investigating the Dependence of 2D and 3D Scatter-To-Primary Ratios on
      Breast Density in Clinical Breast CT.
AB  - PURPOSE: To characterize 2D and 3D scatter-to-primary ratios (SPR) and
      investigate the dependence of SPR on breast density based on clinicalpatient
      imaging on our dedicated SPECT-CT mammotomography system. METHODS: As a part of
      an on-going IRB approved protocol, 7 consented women underwent a breast imaging
      study with our SPECT-CT system. Using a quasi-monochromatic x-ray cone beam and
      flat panel detector, 240 projections were obtained. 6 beam stop array (BSA)
      projections were also obtained over 40 degree intervals. The CT data were scatter
      corrected using a phantom-validated algorithm based on the BSA technique. For
      each projection, 2D scatter fluence was determined behind each beam stop shadow
      through the patient's breast, and cubic spline interpolated throughout the
      thresholded breast region. 2D SPRs were calculated as the average of 6 measured
      ratios of scatter projections to scatter corrected (primary) projections. Angular
      cubic spline interpolation was performed to obtain the remaining 234 azimuthal
      BSA projections for reconstruction correction. Corrected and uncorrected
      projection images were individually reconstructed and 3D SPRs calculated as the
      ratio of difference between primary and un-corrected volumes to primary volumes.
      Histograms of the reconstructed patient data-sets yielded distinct peaks
      representing linear attenuation coefficients of glandular+skin and fatty tissue.
      Percentage glandular and fatty tissue was estimated by fitting a double Gaussian
      to the histogram and integrating area under the curve. RESULTS: Only 4 CT data
      sets devoid of motion and truncation artifacts were suitable for scatter
      correction. Preliminary results show that 2D SPR values peak at the center of
      breast volumes and were greatest (~50%) for the most glandular breast, whereas 3D
      SPR values remained fairly constant throughout the breast and did not obviously
      correlate with density, consistent with prior phantom results. CONCLUSIONS: 2D
      SPR values are greater in breasts with higher glandular tissue composition,
      whereas 3D SPR values appear independent of breast composition. This work is
      funded by the National Cancer Institute of the National Institutes of Health
      grant RO1-CA096821, with partial support (JHP) from NIH T32-EB001040. MPT is the
      inventor of this CT technology, and is named as an inventor on the patent for
      this technology awarded to Duke University. If this technology becomes
      commercially successful, MPT and Duke could benefit financially.

PMID- 28519533
TI  - SU-E-I-40: Effective Dose Normalized to Dose Length Product for Pediatric and
      Adult Reference Phantoms in Computed Tomography Examinations.
AB  - PURPOSE: To develop a set of conversion factors from dose length product (DLP) to
      effective dose (E) for pediatric and adult reference individuals undergoing
      computed tomography (CT) examinations. METHODS: This study used 12 hybrid
      computational phantoms representing reference pediatric and adult individuals in
      compliance with the International Commission on Radiological Protection (ICRP)
      reference data. The phantoms were combined with a model of the Siemens Sensation
      16 scanner, to compute organ doses from CT examinations using a radiation
      transport code, MCNPX2.7. Effective doses based on ICRP 60 and 103 tissue
      weighting factors were calculated. The DLP was derived from the scan length and
      Computed Tomography Dose Index (CTDI)vol. The resulting DLP-to-E conversion
      factors were analyzed. RESULTS: The results consist in a set of DLP-to-E
      conversion factors for head, chest, abdomen, abdomen-pelvis, and chest-abdomen
      pelvis CT examinations for newborn, 1-, 5-, 10-, 15-year-old and adult reference
      phantoms, for 80, 100 and 120 kVp and for ICRP 60 and 103 tissue weighting
      factors. The DLP-to-E factors decrease with smaller tube potential, with the
      greatest decrease for the head examinations for which values at 80 kVp are 20%
      smaller than at 120 kVp on average. The ICRP 103 weighting factors, compared to
      ICRP 60, Result in variations of DLP-to-E from 0.8 to 1.2-fold with a systematic
      increase for the chest, 1.14- fold on average, due to the increased breast
      weighting factor. The DLP-to-E factors for the body examinations are relatively
      similar to each other but 5 to 12-fold higher than for the head exam. The factors
      decrease with age until 15 years and then slightly increase for adult except for
      head. CONCLUSIONS: An updated set of DLP-to-E conversion factors were established
      based on more realistic human phantoms and provide an improved accuracy to obtain
      effective dose from DLP for patients undergoing CT examinations.

PMID- 28519534
TI  - SU-E-I-12: Analysis of Image Noise in 3D Scatter Corrected Cone Beam CT Images as
      a Function of Object Size.
AB  - PURPOSE: To characterize the spatial correlation of quantum noise of a cone beam
      CT (CBCT) system for breast imaging under scatter and non-scatter corrected
      conditions as a function of object radius. METHODS: Experiments were conducted
      using a conical phantom under scatter and non-scatter corrected conditions. The
      cone phantom filled with 700ml of water was positioned near the isocenter of the
      quasi-monochromatic CBCT imaging system. 360 projections were acquired and beam
      stop measured scatter correction was performed. Both scatter and non-scatter
      corrected projections were reconstructed with an iterative ordered subsets convex
      (OSC) algorithm. NPS measurements were made at several cone radii (6-12cm) using
      4 overlapping 50*50 pixel ROI's with a 50% overlap between adjacent ROIs. An
      ensemble average of NPS measurements was taken over 5 slices at each radius.
      RESULTS: For both scatter and non-scatter corrected data overall noise is higher
      with increasing object radius. Each 1-D NPS area under the curve was found to be
      within the standard deviation of the respective ROI variance. The variance of
      scatter corrected images is higher at each radius. The 1-D NPS indicates a
      decrease in peak value for both scatter and non-scatter corrected images as
      radius increases. Scatter corrected NPS shows a slight shift in the peak towards
      higher spatial frequencies, and a larger spread of noise over all spatial
      frequencies as radius increases. CONCLUSIONS: This work demonstrates that scatter
      correction increases noise at each spatial frequency at various object radii.
      owever as radius increases, lower frequency noise decreases and concomitantly
      higher frequency noise increases. As a Result of this equalization of noise
      across spatial frequencies, the noise texture appears more uniform at larger
      radii under scatter corrected conditions. These results and methodology can be
      used to determine optimal detection of low contrast signals in phantoms of
      different radii and with clinical breast data.

PMID- 28519535
TI  - SU-E-I-50: The ACR CT Dose Index Registry: Implementation Challenges and
      Preliminary Data.
AB  - PURPOSE: To successfully register our institution into the American College of
      Ragiology (ACR) CT Dose Index Registry (DIR), to discuss the technical and
      implementation challenges of doing so, and to review preliminary results.
      METHODS: TRIAD is the American College of Radiology Imaging Network's (ACRIN)
      image acquisition and management software, with the purpose of receiving and then
      transmitting DICOM structured dose report files from institutional CT scanners
      around the country. TRIAD was installed onto a virtual machine server at our
      institution so that anonymized and encrypted DICOM structured dose report files
      from our 6 CT scanners could be sent to the TRIAD Application Server at ACR.
      Doing so required collaboration between ACR and IT, PACS personnel and the
      physicist on site. Implementation involved several challenges, such as software
      installation and data transmission consistency problems. Since numerous
      institutions are involved, the ACR required an exam mapping process via the
      Radlex playbook to unify the protocol classification. These challenges have been
      overcome and data is being successfully transmitted to and analyzed by the ACR.
      RESULTS: The first report comparing dose data (CTDI and DLP by examination and by
      scan) between our site and others around the region and country was made
      available recently. For each exam, the report includes boxplots and histogram
      data for a variety of standard protocols. For example, for a CT head exam, our
      median CTDIvol and DLP were 44 mGy and 736 mGy-cm compared with 64 mGy and 844
      mGy-cm respectively, for all other facilities registered in the DIR. CONCLUSIONS:
      The ACR CT DIR registry is a useful tool for dose data mining and will eventually
      establish national benchmarks for CT dose indices. Our experience will allow
      others to anticipate these challenges and have potential solutions available for
      when they do arise.

PMID- 28519536
TI  - SU-E-I-22: Metal Artifact Correction Using KV and Selective MV Imaging.
AB  - PURPOSE: To improve the image quality of radiotherapy planning CTs for patients
      with metal implants or fillings by completing the missing kV projection data with
      selectively acquired MV data that does not suffer from photon starvation. Using
      both imaging systems that are available on current radiotherapy devices,
      streaking artifacts are avoided and the soft tissue contrast is restored, even in
      areas where the kV photons do not contribute any information. This enables a
      better delineation of structures of interest in planning CT images for patients
      with metal objects. METHODS: An algorithm for combining kV and MV projection data
      from the two on-board imagers of a radiotherapy device is presented in this work.
      It only requires selective MV imaging with the high energy X-rays being
      collimated onto the metal implants, ensuring that the patient dose does not
      increase significantly. The algorithm can cope with non-identical geometries of
      the two imagers and is based on stitching together kV and MV sinograms by
      estimating a ratio between them. A numerical head phantom with two dental
      fillings and two soft tissue patterns was used to quantitatively evaluate the
      proposed hybrid reconstruction algorithm. A structural similarity index (SSIM)
      with respect to the ground truth data was computed for two ROIs. Realistic,
      polychromatic spectra were used for both imagers with 120 keV(p) and 6 MeV(p).
      The patient dose was limited to about 6 cGy for both acquisitions combined.
      RESULTS: The reconstruction results yield visually as well as objectively better
      results (SSIM=74.8%) than a simple sinogram interpolation of the kV data
      (SSIM=69.7%) or a reconstruction from the original data (SSIM=17.9%).
      CONCLUSIONS: We have successfully implemented a new reconstruction method for
      hybrid kV-MV cone beam CT reconstruction that enables a better planning of
      radiotherapy treatments for patients with metal implants without compromising
      their safety. This work was funded by NIH grant 1R01CA138426-01A1.

PMID- 28519537
TI  - SU-E-I-33: Advances in Dose Metrics and Dose Reduction Strategies for
      Interventional Fluoroscopy.
AB  - PURPOSE: To explore recent advances in available dose metrics and dose reduction
      features and their impacts during various fluoroscopy procedures. METHODS:
      Besides traditional dose metrics (cumulative dose, DAP, etc), recent methods such
      as real time dose mapping and dose calculation from DICOM information and their
      relevance to entrance skin exposure (ESE) are demonstrated. Dose reduction
      features and their potential effects on ESE are explored for different
      interventional procedures, including dose setting options, frame rate settings,
      wedges, software options and how these help reduce patient dose, etc. Real time
      dose monitoring techniques such as DoseAware are investigated. Dose alert such as
      flagging higher doses at about half of the Joint Commission sentinel event limit,
      Dose Index Registry and their impacts are discussed. Habit related practices,
      such as a physician leaning over patients, are highlighted, also taking foot off
      the fluoroscopy pedal when not needed, and best places to stand are illustrated.
      A practice improvement procedure involving measurement, analysis and improvement
      actions is instituted. We also discuss the impact of physician follow up letters
      to patients who might not have reached the JC Sentinel Event limits but may still
      have skin issues. RESULTS: In our institutes, these efforts have led to reduction
      of both patient dose and personnel exposure for interventional procedures. The
      recording of technical parameters and fluoroscopy dose by the staff has led to a
      better understanding of appropriate dose levels and technique settings for each
      procedure. CONCLUSIONS: This article can serve as a refresher for radiological
      staff on how to protect patients and themselves from high doses, while providing
      the best care possible. It can also serve as criteria for health care providers
      to institute changes and make quality improvement in interventional practices.

PMID- 28519538
TI  - SU-E-I-05: Dose Reduction in Head CBCT Examinations After Protocol Optimization.
AB  - PURPOSE: CBCT systems for head examinations especially in otorhinolaryngology
      offer better than required image quality at relatively low purchasing costs. Due
      to this fact the number of dedicated head scanners increases steadily. Regarding
      image quality in relation to patient dose these systems are frequently not
      optimized. Examination parameter optimization is an iterative process, which
      should be done carefully by physicians in cooperation with physicists. After a
      successful optimization, Monte Carlo Simulations can be used to quantify the dose
      reduction to the patient. METHODS: Images of an anatomic head phantom were
      obtained using different settings of kVp, mAs and rotation angle (360 degrees ,
      210 degrees ). The resulting images were anonymized and the examination
      parameters were removed. Radiologists and otorhinolaryngologists evaluated these
      images and rated them into excellent image quality, good image quality, bad image
      quality and not readable. Based on the ratings new parameters for the adequate
      image quality were set. The dose reduction was calculated using Monte Carlo
      simulations. RESULTS: The organ dose of radiation sensitive organs was reduced
      significantly. The dose reductions compared to the standard settings are: eyes:
      85%, eye lenses: 88%, salivary glands: 40%, thyroid: 60%, blood vessels: 40%,
      brain: 60%, teeth: 80% and tonsils: 65%. Dose reduction was best, when a short
      scan (210 degrees  rotation angle) was used, where the eyes are not in the direct
      exposure field. CONCLUSIONS: The results show the potential for dose
      optimizations in otorhinolaryngological CBCT examinations compared to standard
      vendor settings without loss in diagnostic information. Furthermore this study
      points out the great opportunities that Monte Carlo-based dose-calculations
      methods offer to quantify the increase of dose efficiency after examination
      protocol optimizations. It could also be shown that CBCT has advantages when
      doing short scan mode around the rear head. This protects radiation sensitive
      organs such as the eye lenses from being directly radiated.

PMID- 28519539
TI  - SU-E-I-44: The UF/NCI Family of Hybrid Computational Phantoms Representing the
      Current US Population of Male and Female Children and Adolescents Applications to
      CT Organ Dosimetry.
AB  - PURPOSE: To assist in the rapid reporting of patient organ doses, researchers at
      the University of Florida and the National Cancer Institute have developed a
      family of computational hybrid phantoms, constructed from NURBS and polygon mesh
      surfaces, that fully represent the ICRP 89 50th percentile reference newborn, 1
      year-old, 5-year-old, 10-year-old, 15-year- old male and female, and adult male
      and female. Coupled with Monte Carlo simulations, these phantoms can be used to
      estimate patient organ doses. Substantial increases seen in childhood obesity in
      the United States have prompted us to undergo a major revision to the UF/NCI
      phantom library. METHODS: A decision was made to construct the new library in a
      gridded fashion by height/weight without further reference to age-dependent
      weight/height percentiles. At each height/weight combination, secondary
      circumferential parameters are also defined and used for phantom construction.
      All morphometric data for the new library are taken from the CDC NHANES survey
      data over the time period 1999 to 2006, the most recent reported survey period. A
      subset of the phantom library was then used in a CT organ dose sensitivity study
      to examine the degree to which full Monte Carlo simulations would be required to
      track organ doses for patients that are severely underweight to obese in body
      size. RESULTS: Using primary and secondary parameters, a grid containing 85
      pediatric male height/weight bins and a grid containing 73 pediatric female
      height' weight bins were constructed. These grids will provide the blueprints for
      later constructing a comprehensive library of patient' dependent phantoms
      containing 158 pediatric phantoms. CONCLUSIONS: In the future, the UF/NCI phantom
      library will be used to construct pre-computed dose libraries for individuals
      undergoing CT examinations. Ultimately, these libraries can be deployed in the
      clinic for electronic recording of patient organ dosimetry following diagnostic
      imaging procedures.

PMID- 28519599
TI  - WE-G-BRB-08: TG-51 Calibration of First Commercial MRI-Guided IMRT System in the
      Presence of 0.35 Tesla Magnetic Field.
AB  - PURPOSE: The first real-time-MRI-guided radiotherapy system has been installed in
      a clinic and it is being evaluated. Presence of magnetic field (MF) during
      radiation output calibration may have implications on ionization measurements and
      there is a possibility that standard calibration protocols may not be suitable
      for dose measurements for such devices. In this study, we evaluated whether a
      standard calibration protocol (AAPM- TG-51) is appropriate for absolute dose
      measurement in presence of MF. METHODS: Treatment delivery of the ViewRay (VR)
      system is via three 15,000Ci Cobalt-60 heads positioned 120-degrees apart and all
      calibration measurements were done in the presence of 0.35T MF. Two ADCL-
      calibrated ionization-chambers (Exradin A12, A16) were used for TG-51
      calibration. Chambers were positioned at 5-cm depth, (SSD=105cm: VR's isocenter),
      and the MLC leaves were shaped to a 10.5cm * 10.5 cm field size. Percent-depth
      dose (PDD) measurements were performed for 5 and 10 cm depths. Individual output
      of each head was measured using the AAPM- TG51 protocol. Calibration accuracy for
      each head was subsequently verified by Radiological Physics Center (RPC) TLD
      measurements. RESULTS: Measured ion-recombination (Pion) and polarity (Ppol)
      correction factors were less-than 1.002 and 1.006, respectively. Measured PDDs
      agreed with BJR-25 within +/-0.2%. Maximum dose rates for the reference field
      size at VR's isocenter for heads 1, 2 and 3 were 1.445+/-0.005, 1.446+/-0.107,
      1.431+/-0.006 Gy/minute, respectively. Our calibrations agreed with RPC- TLD
      measurements within +/-1.3%, +/-2.6% and +/-2.0% for treatment-heads 1, 2 and 3,
      respectively. At the time of calibration, mean activity of the Co-60 sources was
      10,800Ci+/-0.1%. CONCLUSIONS: This study shows that the TG- 51 calibration is
      feasible in the presence of 0.35T MF and the measurement agreement is within the
      range of results obtainable for conventional treatment machines. Drs. Green,
      Goddu, and Mutic served as scientific consultants for ViewRay, Inc. Dr. Mutic is
      on the clinical focus group for ViewRay, Inc., and his spouse holds shares in
      ViewRay, Inc.

PMID- 28519600
TI  - WE-G-211-02: Origins and Development of Magnetic Resonance Imaging.
AB  - The method of magnetic resonance imaging (MRI) was an extension of nuclear
      magnetic resonance (NMR) spectroscopy that was enabled by computational systems
      capable of performing the Fast Fourier Transform. Initially, a diverse group of
      methods were proposed for producing images with NMR, with the multi-slice spin
      warp spin echo MRI method winning out as the first clinically useful approach.
      Immediately radiologists were impressed in the soft tissue contrast seen in MR
      images and the great flexibility with which image contrast could be manipulated.
      Over the years, advances in both hardware and the implementation of new pulse
      sequences of increasing complexity led to the increasing utility of MRI. The
      great success of MRI research contributed to the awarding of both the Nobel Prize
      in Chemistry for Richard Ernst in 1991 and the Nobel Prize in Physiology or
      Medicine for Lauterbur and Mansfield in 2003. The evolution of the modality
      produced increasing speed of acquisition, finer spatial resolution and an
      expanding range of clinical applications. Technological advances included
      improvements in gradient coils, superconducting magnets, phased array
      radiofrequency coils, and partially parallel image reconstruction algorithms. The
      wide range of applications developed include MR angiography, BOLD contrast
      functional MRI, and diffusion-weighted MRI. This section of the symposium will
      conclude with a look a current developments and where they are likely to take the
      field into the future.

PMID- 28519601
TI  - WE-G-BRB-01: Per-Frame Analysis of MatriXX Data.
AB  - PURPOSE: One of the most widely used IMRT QA devices (MatriXX) is an array of
      ionization chambers which are periodically read during plan delivery. Although
      the ionization chambers are not expected to exhibit strong angular dependence,
      the measured dose distribution is often found to significantly differ from the
      planned dose distribution. We identify the origin of all factors that affect the
      measurement accuracy of the MatriXX and develop a per-frame post-processing
      strategy that reduces their impact on the passing rate of IMRT and VMAT plans.
      METHODS: We developed software that reads the dose frame sequence recorded by the
      MatriXX and applies a number of correction factors to each frame. Angular
      correction factors are computed as ratios of measured dose at the isocenter of
      the phantom and planned dose at the same location for all clinically used photon
      energies. For every clinical case, the recorded movie file is read and the dose
      for every frame is corrected according to the angle of the beam. In addition, the
      background evolution is tracked in the 'beam-off' frames which are subsequently
      subtracted from the 'beam-on' frames according to a predictive model. Machine
      output correction is also implemented, which significantly improves the absolute
      dose measurements. The IMRT effective plane of measurement of the MatriXX was
      identified and found not to coincide with the isocentric plane. RESULTS: The
      clinical passing rates are significantly improved when the per-frame analysis
      software was introduced in our IMRT QA procedure. For a group of 800 patients
      with no corrections the average passing rate was 93.6%, while for the first 300
      cases with per frame corrections the average passing rate was 97.3%. CONCLUSIONS:
      We identify all factors that impact the measurement accuracy of the MatriXX
      (angular effects, background evolution, machine output, plane of measurement) and
      propose a strategy for their elimination.

PMID- 28519602
TI  - WE-G-BRA-03: Enhancing Medical Imaging Physics Education on a Global Basis with
      Shared Resources.
AB  - PURPOSE: To enhance and enrich medical imaging physics education by first
      translating personal professional experience into highly-effective educational
      resources and then sharing with both learners and medical physics educators on a
      global basis as an open and free resource. METHODS: Effective medical imaging
      physics education that contributes to high-quality and safe clinical procedures
      requires medical physicists and students, anywhere in the world, having access to
      the science of contemporary imaging methods and procedures in a form that
      enriches both the teaching and learning activities. This is being achieved in two
      phases. The first (and continuing) phase is the translation of personal
      experience as a practicing clinical medical physicist in to a synergistic
      collection of educational resources including textbooks, online modules, and
      especially highly- effective visuals that can be used in classroom presentations
      and small group discussions. It is the availability of these visuals that
      enhances the performance of medical physicists as teachers who can devote their
      efforts to guiding the class learning activities and sharing their personal
      experiences and not be burdened with the production of extensive teaching
      materials. The second (and overlapping) phase is the development of a model and
      method for sharing as an open and free resource. This is achieved through a web
      site developed for that purpose, www.(blinded for review).org. RESULTS: These
      resources are used to support medical physics educators, programs, and individual
      learners both in the US and in over 100 different countries with an average of
      over 1000 users each day. CONCLUSIONS: The production and sharing of educational
      resources by an individual medical physicist complements and extends beyond the
      programs and activities of institutions and organizations. It is of significant
      value to learners anywhere in the world because the availability is not limited
      by costly course enrollment, membership, meeting registration, or geographic
      restrictions.

PMID- 28519603
TI  - WE-G-218-02: The Measurement of Absorbed Dose to Active Intravenous Cardiac
      Devices in Patients Undergoing Radiotherapy.
AB  - : Radiotherapy departments are seeing an increasing number of patients presenting
      for treatment with active intravenous cardiac devices (AICDs). This is due to an
      increasing aging population and technology advances in these devices. The AAPM TG
      34 addressed the radiation effects in these devices and provided recommendations
      for patients with these devices undergoing radiotherapy. The current devices
      utilizing CMOS technology are more sensitive to radiation then the older bipolar
      devices. Therefore, it is important to estimate the dose to the device to ensure
      that the radiation does not adversely affect the performance of the device. This
      is particularly important for patients dependent on their accurate functioning.
      The dose to the device is generally from secondary radiation and is typically
      below 0.05 Gy with most of it coming from lower energy scatter radiation.
      Treatment planning systems can be used to estimate the dose to the device.
      However, these systems do not accurately calculate doses at distances more than 2
      3 cm from the field edge. For these out-of-field dose measurements the dosimeter
      requires a high sensitivity and a relatively flat energy response.
      Thermoluminescent detectors and optically stimulated luminescent detectors
      satisfy these requirements and they are relatively unobtrusive. The newer
      formulations of radiochromic film with higher sensitivity can also be used. The
      detector should be place under 0.5 to 1.0 cm of bolus to minimize the
      contaminating head-scatter electrons provide a more realistic measurement of the
      dose to the device. LEARNING OBJECTIVES: 1. List the reasons for estimating the
      dose to the AICDs 2. Provide a discussion on the various methods which include
      calculations and measurements to estimate the dose to the device as well as the
      uncertainties in these estimates. 3. Identify detectors that satisfy the
      requirements for these in-vivo out-of-field dose measurements as well as describe
      the appropriate correction factors to apply for accurate dose measurements.

PMID- 28519604
TI  - WE-G-BRA-06: Calibrating an Ionisation Chamber: Gaining Experience Using a
      Dosimetry 'flight Simulator'.
AB  - PURPOSE: Recently there has been great interest in the use of simulation
      training, with the view to enhance safety within radiotherapy practice. We have
      developed a Virtual Environment for Radiotherapy Training (VERT) which
      facilitates this, including the simulation of a number of 'Physics practices'.
      One such process is the calibration of an ionisation chamber for use in Linac
      photon beams. METHODS: The VERT system was used to provide a life sized 3D
      virtual environment within which we were able to simulate the calibration of a
      departmental chamber for 6MV and 15 MV beams following the UK 1990 Code of
      Practice. The characteristics of the beams are fixed parameters in the
      simulation, whereas default (Absorbed dose to water) correction factors of the
      chambers are configurable thereby dictating their response in the virtual x-ray
      beam. When the simulation is started, a random, realistic temperature and
      pressure is assigned to the bunker. Measurement and chamber positional errors are
      assigned to the chambers. A virtual water phantom was placed on the Linac couch
      and irradiated through the side using a 10 * 10 field. With a chamber at the
      appropriate depths and irradiated iso-centrically, the Quality Indices (QI) of
      the beams were obtained. The two chambers were 'inter-compared', allowing the
      departmental chamber calibration factor to be calculated from that of the
      reference chamber. RESULTS: For the virtual 6/15 MV beams, the QI were found to
      be 0.668/ 0.761 and the inter-comparison ratios 0.4408/ 0.4402 respectively. The
      departmental chamber calibration factors were calculated; applying these and
      appropriate environmental corrections allowed the output of the Linac to be
      confirmed. CONCLUSIONS: We have shown how a virtual training environment can be
      used to demonstrate practical processes and reinforce learning. The UK CoP was
      used here, however any relevant protocol could be demonstrated. Two of the
      authors (Beavis and Ward) are Founders of Vertual Ltd, a spin-out company created
      to commercialise the research presented in this abstract.

PMID- 28519606
TI  - WE-G-217A-04: Segmenting Limbic Circuit Fiber Tracts for Quantifying Changes in
      Diffusion Indices Due to Partial Radiation Therapy.
AB  - PURPOSE: To segment the cingulum, fornix and the corpus callosum using diffusion
      weighted images, in order to evaluate the radiation-induced damage on these
      important white matter structures Methods: We propose a seed-based tractography
      algorithm for segmenting the entire cingulum into the left and right anterior,
      superior, and posterior subdivisions. In that algorithm, multiple ROIs (regions
      of interest) for tractography are automatically created from seeded points by a
      level-set segmentation algorithm. Moreover, we propose new ROI placements for
      fornix tractography. Furthermore, a new subdividing method is proposed for
      supporting the possible rotation in the corpus callosum longitudinal axis in
      presence of glioma tumors. To test the reproducibility of the proposed algorithm
      for segmenting the cingulum, test-retest diffusion tensor data-sets of twelve
      patients were chosen from the National Biomedical Imaging Archive database. We
      calculated the Dice coefficients of the volumetric overlap between the test and
      retest cingulum segments. Twenty-two patients with low grade brain gliomas
      underwent 6-week fractionated radiation therapy (RT). The patients prospectively
      enrolled MRI with diffusion tensor imaging up to 18 months after starting RT. The
      fornix and subdivisions of cingulum and corpus callosum were segmented. RESULTS:
      The Dice coefficients between test and retest data were 0.878, 0.899, 0.951,
      0.954, 0.926, and 0.929 for the anterior right and left, the superior right and
      left, and the posterior right and left cingulum segments respectively, suggesting
      our method's high reproducibility. Amongst the fornix and subdivisions of
      cingulum and corpus callosum, the most significant changes in fractional
      anisotropy, mean, axial, and radial diffusivity were observed in fornix
      throughout all dose volumes, indicating that both axonal degradation and
      dysmyelination are prominent radiation effects in the fornix. CONCLUSIONS: The
      proposed seed-based tractography method segments the cingulum accurately and
      completely with dramatically reducing the operator's interaction time and effort
      in manual depicting large number of ROIs. Supported in part by National
      Institutes of Health grants RO1 NS064973.

PMID- 28519607
TI  - WE-G-213CD-04: A Triggering System to Guide 4DMRI Image Acquisition.
AB  - PURPOSE: To develop a practical triggering system based on pre-selected
      respiratory amplitudes to guide prospectively the image acquisition of 4DMRI to
      track abdominal tumor motion for radiotherapy treatment planning. METHODS: The
      proposed triggering scheme consists of a preparation stage and an acquisition
      stage. Immediately prior to MRI acquisition, the preparation stage monitors the
      respiration via an external respiratory belt. Based on the respiratory amplitude
      and status (i.e., inhalation? or exhalation?), the respiration cycle is equally
      divided into N respiratory states. For example, in the 4-state case, the 4
      respiratory states are 5%?", 50%?, 95%? and 50%?. The 5%? and 95%? are used
      instead of 0% and 100% to improve the robustness of the triggering system. Each
      state is associated with a trigger which starts image acquisition for one and
      only one slice. A complete 4DMRI imageset requires N dynamic scans. In each
      dynamic scan, all slices are acquired once and each is in a specific respiratory
      state. In different dynamic scans, each slice is associated with different
      respiratory states to form a 4D dataset. For proof-of-principle, the triggering
      system was integrated into a T2-weighted turbo spin echo sequence (TE=100ms,
      TR=7122ms) on a clinical 1.5T MRI (Philips Achieva) scanner. The 4-state case was
      tested on a healthy subject. RESULTS: Plots of the physiology data recorded and
      exported from the scanner clearly verified that triggers occurred at the expected
      locations. Four T2-weighted images from a representative slice recorded the liver
      motion corresponding to the 4 respiratory states. CONCLUSIONS: Our results
      confirmed that the newly-developed system could trigger prospectively to guide
      4DMRI image acquisition to achieve T2 weighting, which has a better tumor-tissue
      contrast than those offered by previous 4DMRI techniques with T1 or T2/T1
      weighting. This is a first report of a pure T2-weighted 4DMRI to track
      respiration induced abdominal motion.

PMID- 28519608
TI  - WE-G-217BCD-08: Image Quality Effects of Dynamic Iodine Concentrations for
      Contrast-Enhanced Cone-Beam CT.
AB  - PURPOSE: To study the image effects of the time-wise dynamic aspect of
      intravenous contrast agents to enable contrast-enhanced cone-beam CT (CE- CBCT)
      localization of liver lesions for stereotactic body radiation therapy (SBRT).
      METHODS: A model was developed to study dynamic IV contrast agents using static
      phantoms and to derive optimum parameters for CE- CBCT imaging. Ten samples
      containing iodine at 0-5 mg/mL were prepared in cylindrical tubes, corresponding
      roughly to 0-100 HU as measured by 120 kV helical CT imaging. Each sample was
      imaged separately in a tissue- equivalent phantom, yielding ten datasets (roughly
      650 projections each) corresponding to these static CBCT images. To reconstruct
      images of dynamic contrast concentrations, the CBCT 2D projections were re-
      assembled to match the expected amount of contrast at different points in time.
      This model was applied to published hepatic contrast enhancement curves, and
      optimum imaging and contrast injection parameters were derived. RESULTS: A signal
      to-noise ratio (SNR) decrease of 25%-75% in dynamic CE-CBCT images from ideal CT
      of samples with a 20-100 HU difference from water was observed in the un
      optimized scans. This demonstrates the difficulty of CE-CBCT, and was noticed
      even in geometries that minimize or eliminate x-ray scatter, detector glare, and
      motion. Using our model, we found parameters for iodine injection, CBCT scanning,
      and injection/scanning timing which optimize contrast enhancement, and a 100% SNR
      increase with respect to the un-optimized scans was achieved. CONCLUSIONS: The
      effect of IV contrast is severely degraded in CBCT, and optimization of image and
      timing parameters is crucial for improved CE-CBCT imaging for target
      localization. CBCT has very low temporal resolution, and the pharmacokinetics of
      IV contrast must be carefully considered in order to apply this technique to
      localize liver lesions for SBRT. This model will be used to establish the
      feasibility of CE- CBCT for routine localization of liver lesions.

PMID- 28519609
TI  - WE-G-BRCD-05: Evaluation of Localization Errors for CSA Delivery Using VMAT.
AB  - PURPOSE: To dosimetrically evaluate the effects of improper patient positioning
      in the junction area of a VMAT cranio-spinal axis irradiation technique
      consisting of one superior and one inferior arc. METHODS: Five (n=5) cranio
      spinal axis irradiation patients were planned with 2 arcs: one superior and one
      inferior. The plans were then recalculated with inferior isocenter shifted, in
      order to mimic patient setup errors, eight times: lmm, 2mm, 5mm, and 10mm
      superiorly, and 1mm, 2mm, 5mm, and 10mm inferiorly. Plans were then compared to
      the original, non-shifted arc plan based on target metrics of conformity number
      and homogeneity index, as well as several normal structure mean doses. RESULTS:
      Percent differences were calculated in order to compare each of the eight shifted
      plans to the original arc plan without shifts, which would be the ideal setup of
      patient without error. The conformity number was on average 0.87%, 2.74%, 5.75%,
      and 9.10% lower for the 1mm, 2mm, 5mm, and 10mm inferiorly- shifted plans and
      0.41%, 0.82%, 2.75%, and 5.99% lower for the respective superiorly-shifted plans.
      The homogeneity indices were, averaged among the five patients, 0.03%, 0.26%,
      0.97%, and 2.84% for the inferior shifts and 0.23%, 1.17%, 6.31%, and 15.29%
      worse, or less homogenous for the superior shifts. Overall the mean doses to the
      organs at risk were less than 2% different for the 1mm, 2mm, and 5mm shifted
      plans. The 10mm shifted plans, however, showed percent differences from original
      plan of up to 5.6% on average. CONCLUSIONS: Setup errors when shifting isocenters
      should be minimized in order to provide the patient with the best treatment
      possible. Errors of 1 to 2mm can negatively affect patient treatment, most
      notably in the arc junction area, but are not as problematic as larger errors of
      5 to 10mm.

PMID- 28519605
TI  - WE-G-217BCD-04: Diagnostic Image Quality Evaluation of a Dedicated Extremity Cone
      Beam CT Scanner: Pre-Clinical Studies and First Clinical Results.
AB  - PURPOSE: To assess the diagnostic performance of a prototype cone-beam CT (CBCT)
      scanner developed for musculoskeletal extremity imaging. Studies involved
      controlled observer studies conducted subsequent to rigorous technical assessment
      as well as patient images from the first clinical trial in imaging the hand and
      knee. METHODS: Performance assessment included: 1.) rigorous technical
      assessment; 2.) controlled observer studies using CBCT images of cadaveric
      specimens; and 3.) first clinical images. Technical assessment included
      measurement of spatial resolution (MTF), constrast, and noise (SDNR) versus kVp
      and dose using standard CT phantoms. Diagnostic performance in comparison to
      multi- detector CT (MDCT) was assessed in controlled observer studies involving
      12 cadaveric hands and knees scanned with and without abnormality (fracture).
      Observer studies involved five radiologists rating pertinent diagnostics tasks in
      9-point preference and 10-point diagnostic satisfaction scales. Finally, the
      first clinical images from an ongoing pilot study were assessed in terms of
      diagnostic utility in disease assessment and overall workflow in patient setup.
      RESULTS: Quantitative assessment demonstrated sub-mm spatial resolution (MTF
      exceeding 10% out to 15-20 cm-1) and SDNR sufficient for relevant soft-tissue
      visualization tasks at dose <10 mGy. Observer studies confirmed optimal
      acquisition techniques and demonstrated superior utility of combined soft-tissue
      visualization and isotropic spatial resolution in diagnostic tasks. Images from
      the patient trial demonstrate exquisite contrast and detail and the ability to
      detect tissue impingement in weight-bearing exams. CONCLUSIONS: The prototype
      CBCT scanner provides isotropic spatial resolution superior to standard-protocol
      MDCT with soft-tissue visibility sufficient for a broad range of diagnostic tasks
      in musculoskeletal radiology. Dosimetry and workflow were advantageous in
      comparison to whole-body MDCT. Multi-mode and weight-bearing capabilities add
      valuable functionality. An ongoing clinical study further assesses diagnostic
      utility and defines the role of such technology in the diagnostic arsenal. -
      Research Grant, Carestream Health - Research Grant, National Institutes of Health
      2R01-CA-112163.

PMID- 28519610
TI  - WE-G-217A-08: Routine ACR SNR Measurement Failed to Detect 32-Channel Head Coil
      Receiver Malfunction.
AB  - PURPOSE: To study if malfunction of a receiver can be detected robustly using the
      simple ACR SNR measurement approach on a 32-channel head coil. METHODS: Standard
      ACR T1W images (11slice) were acquired with a commercial 32 channel head coil on
      a 3T Philips Achieva MR scanner following the ACR recommended setup. Raw data
      were saved and were used to reconstruct 32 image datasets, each with one coil
      channel turned off and signal were excluded from reconstruction. Routine simple
      SNR evaluation method was used to measure SNR for each dataset. Specifically,
      region of interest (ROI) analysis was performed on slice #7 for each dataset.
      Signal was the mean value of the pixel intensity measured using an ROI with area
      of 200 cm2 positioned at the center of phantom. Noise was the standard deviation
      derived from an ROI positioned in the background in a corner of the image. SNR
      was then calculated from signal divided by noise. For comparison purposes, we
      empirically chose 5% SNR drop compared to the full 32 channel dataset SNR as a
      significant SNR drop that is correlated a potential coil channel defect. RESULTS:
      Among the 32 image datasets reconstructed each with one receiver turned off, only
      4 showed SNR drop of more than 5% or more compared to the reference SNR obtained
      from the original dataset. Four other datasets had SNR drop between 0.1-5%. The
      rest (24 image sets) did not show any SNR drop. Therefore, SNR monitoring based
      on the large ROI approach as the routine ACR QC procedure failed detect receiver
      malfunction in this coil. CONCLUSIONS: More advanced and thorough coil evaluation
      methods, instead of the routine simple ACR SNR measurement method, have to be
      applied to evaluate the performance of the phased-array head coil with 32 or more
      channels.

PMID- 28519611
TI  - WE-G-BRB-07: Application of RADPOS in Vivo Dosimetry for QA of High Dose Rate
      Brachytherapy.
AB  - PURPOSE: The RADPOS in vivo dosimetry system combines an electromagnetic
      positioning sensor with MOSFET dosimetry, allowing for simultaneous online
      measurements of dose and spatial position. In this work, we assess the potential
      use of RADPOS for measurements of motion and dose during prostate HDR
      brachytherapy. METHODS: The RADPOS was positioned in the centre of a thin plastic
      tube supported by two parallel acrylic plates submerged in water. The detector
      was calibrated by sending an Ir-192 source into an adjacent tube, to positions
      ranging from 8.0 to -8.0 cm along the vertical axis in increments of 0.5 cm. The
      dwell time at each position was 20 s and the change in threshold voltage of the
      RADPOS dosimeter was recorded for each position. The expected dose for each
      source position was calculated and compared to RADPOS measurements to obtain a
      detector calibration coefficient (cGy/mV). The procedure was then repeated
      sending the Ir-192 source into 5 other tubes, located 1 to 10 cm away from the
      RADPOS. Source positions, dwell times, and position of the RADPOS detector were
      the same as for the calibration. The dose for each source position was determined
      by RADPOS measurements and calibration coefficient and compared to the expected
      dose. RESULTS: An average calibration coefficient of 0.74+/-0.11 cGy/mV was
      calculated for RADPOS measurements of Ir-192 irradiations. The absolute
      difference between RADPOS values and expected dose for subsequent measurements
      averaged over all source positions was 0.7+/-5.4 cGy. CONCLUSIONS: In vivo
      dosimetry can potentially signal errors in catheter placement or numbering before
      entire dose is delivered. The demonstrated accuracy of RADPOS dose measurements
      and its ability to simultaneously measure displacement makes it a powerful tool
      for HDR brachytherapy treatments for prostate cancer, where high dose gradients
      and movement of the prostate gland can present unique in vivo dosimetry
      challenges. Financial and technical support has been received from Best Medical
      Canada and Ascension Technology Corporation.

PMID- 28519612
TI  - WE-G-213CD-08: Initial Experience with the Clinical Implementation of a Deep
      Inspiration Breath Hold for Left Breast Radiotherapy Using Surface Imaging and
      Visual Aid.
AB  - PURPOSE: To evaluate the clinical implementation of a deep inspiration breath
      hold (DIBH) treatment for left breast radiotherapy using surface imaging and
      visual aid. METHODS: A CT scan of the patient at DIBH is acquired and used for
      treatment planning. The plan and skin contour, containing isocenter and surface
      information are exported from the treatment planning system and imported into the
      surface imaging system (SIS). The skin contour constitutes the treatment
      reference surface or target DIBH position. A region of interest (ROI) consisting
      of the sternum and medial breasts is selected in the SIS. A set of video goggles
      allows the patient to view their breathing signal within the SIS, aiding in
      producing a reproducible and stable DIBH similar to simulation. Once the patient
      is set up at free breathing, she performs a DIBH while being monitored with the
      SIS. Shifts to minimize displacements from their reference DIBH surface are made.
      The surface image and patient setup are validated with weekly MV images. The beam
      is enabled when the two surfaces are within a predetermined tolerance. RESULTS:
      Data for evaluation of the implementation was acquired for 4 patients throughout
      treatment. Average treatment time was 16.8 minutes and 14.2 minutes for setup.
      The average displacement from the reference surface was 0.4 mm during DIBHs. The
      average reduction of heart mean dose and volume receiving 50% of the prescribed
      dose between DIBH and FB was 38% and 89% respectively. A total of 15 patients
      have completed this new treatment. 2 were excluded for inability to achieve
      reproducible and stable DIBH. CONCLUSION: The workflow we have implemented has
      proven to be effective and efficient for clinical purposes. Surface imaging
      provides adequate real time information valuable to the treatment process. Visual
      aid has helped patients achieve DIBH with high reproducibility and stability.

PMID- 28519613
TI  - WE-G-211-01: Cross-Sectional Imaging - Computed Tomography.
AB  - The introduction of new cross-sectional imaging techniques in the 1970's and
      1980's led to great improvements in the diagnosis and treatment of medical
      conditions. In this symposium, we will chronicle the development of three of
      these Methods: computed tomography (CT), magnetic resonance imaging (MRI), and
      ultrasonic imaging (US). Computed Tomography Early attempts to obtain trans-axial
      radiographs employed unconventional mechanical motions of the x-ray tube and
      screen-film image receptor that produced images of limited utility. The
      introduction of the EMI Mk I computerized axial tomography (CAT) unit
      revolutionized imaging by providing electronic trans-axial images of the brain
      that allowed clear separation of various tissues with very similar attenuation
      coefficients. The great success of this imaging process led to the Nobel Prize
      for Hounsfield and Cormack in 1979. Examples from the evolution of the x-ray
      computed tomography technique, introduced initially by a large number of
      manufacturers over several "generations" of CT scanners will be presented. The
      changes include improvements in x-ray detectors and detector arrays, image
      reconstruction algorithms, and body bolus/filters, as well as the introduction of
      slip ring technology. These upgrades led to shorter scanning and reconstruction
      times, greater body coverage per rotation, and reduced artifacts, along with
      increased spatial resolution and improved low contrast performance. A very brief
      overview of additional cross sectional x-ray imaging devices and techniques that
      have been developed in recent years will conclude this section of the symposium.

PMID- 28519614
TI  - WE-G-BRCD-09: Assessment of Quantitative Differences Between Different Deformable
      Image Registration Algorithms for Image Guided Radiotherapy of Head and Neck
      Cancer Patients.
AB  - PURPOSE: DIR algorithms differ by physical principles employed in their design
      which in turn determines complexity of the transformation that the algorithm
      allows. Indiscriminate application of different algorithms without regard for
      their limitations may lead to significant discrepancies in research results and
      in clinical procedures. We compare two different algorithms in Head and Neck
      (H&N) patients to assess what aspects of DIR use are most sensitive to
      differences between algorithms. METHODS: H&N patients are enrolled in a protocol
      which acquires weekly FBCT and daily double CBCT. Each FBCT study is contoured by
      the same physician. Two DIR algorithms are compared: Small Deformation Inverse
      Consistent Linear Elastic (SICLE), and the ITK Diffeomorphic Demons (ITKDD) as
      implemented in the ITK package. Both algorithms employ significantly different
      physical principles in their design and consequently impose different
      restrictions on the complexity of transformation they allow. We compare Jacobian
      Volume Histograms (JVH), Spatial Discrepancy Volume Histograms (SDVH), BED and
      physical dose accumulation results and resulting plan evaluation indices.
      RESULTS: Analysis of mean Jacobian shows that both algorithms are able to detect
      changes in structure volumes, though they differ quantitatively from one another
      and from the ground truth as established by the analysis of changes in contours.
      Width of Jacobian distributions is very different indicating that Jacobian should
      not be used as a measure of volume change at a voxel level without independent
      validation. Analysis of SDVHs shows that dose lookup points implied by both
      algorithms are separated by 5mm - 10mm over approximately 30% of most volumes.
      These differences translate into clearly visible though not very significant
      differences in BED and dose accumulation. We further observe that physical dose
      accumulation in external beam H&N patients is a good proxy for direct BED
      accumulation. CONCLUSIONS: Different DIR algorithms may have to be applied
      selectively in different areas of treatment planning. Acknowledgments: Supported
      by NIH Grant P01 CA11602.

PMID- 28519615
TI  - WE-G-BRA-02: Visual Demonstrations of Medical Physics Concepts of Transmission
      Imaging for Resident Education.
AB  - PURPOSE: To improve the radiology residents' understanding of medical physics
      concepts through visualization of physical phenomena. METHODS: Several medical
      physics concepts in x-ray transmission imaging are relevant to many radiographic
      modalities, not only to planar radiography. Therefore, it is important that the
      diagnostic radiology residents obtain a good understanding of these concepts.
      However, standard PowerPoint slides or blackboard-based graphical representations
      are not always effective ways to communicate these novel concepts to the
      residents. To improve upon the understanding of these concepts, the computer,
      projector and screen in the lecture room are used as surrogates of an x-ray
      imaging system. The projector is the source of light (x-rays) with PowerPoint
      slides defining the pattern emitted (x-ray field) on to the projector screen
      (detector/monitor). Several different transparencies and acrylic objects are used
      to demonstrate varied medical physics phenomena relevant to transmission imaging,
      such as: straight-line travel of electromagnetic radiation; tissue
      superimposition; object, subject, image and display contrast; linear systems;
      point spread functions; frequency domain; contrast and modulation transfer
      functions; quantum and image noise; noise frequency and noise power spectrum;
      anatomical noise; magnification and geometric unsharpness; inverse square
      distance relationship; sampling and aliasing; and x-ray scatter. RESULTS: The
      residents' comprehension and ability to explain these concepts has substantially
      improved, in addition to their interest in these topics. This was reflected on
      improved test scores and on anonymous feedback surveys post- lectures.
      CONCLUSIONS: The use of demonstrations that mimic the conditions and physical
      phenomena found in transmission imaging by taking advantage of the projector and
      screen together with transparencies and other objects improves the residents'
      grasp of basic radiographic concepts and promotes live interactions between the
      residents and the medical physicist. Additional concepts that can be demonstrated
      in this manner are being sought.

PMID- 28519616
TI  - WE-G-BRCD-02: Speed Up Standard Optimization of IMPT Treatment Planning Through
      the Application of GPUs.
AB  - PURPOSE: While intensity-modulated proton therapy (IMPT) has great potential to
      deliver highly conformal tumoricidal dose to targets whilst minimizing dose to
      nearby organs-at-risk, IMPT optimization is very time consuming and memory
      extensive due to finer dose grids and a large number of energy layers used
      compared to intensity-modulated radiation therapy (IMRT). In this presentation,
      for the first time, a new approach is introduced to speed up the IMPT treatment
      planning through application of parallel computing with Graphic Processor Units
      (GPUs). METHODS: Parallel computation with GPUs, which are affordable and can be
      plugged in a workstation easily, is potentially a good way to improve the
      computation efficiency. In our approach, we used the standard quadratic objective
      function to optimize the intensity map of beamlets. The objective function and
      gradient equations, which are the most time consuming parts of the optimization,
      were calculated with GPUs. We compared the computation time of optimization done
      by an Intel (r) CoreTM i7 CPU and that by the same CPU accelerated by GPUs (TESLA
      C1060). The influence matrix was pre- calculated before optimization with an in
      house proton pencil beam dose calculation engine. Two clinical cases were
      studied: one base-of-skull (BOS) case (clivus chordoma) and one prostate case
      (adenocarcinoma). The dose volume histogram (DVH) data for the tumor and critical
      organs were derived for comparison of optimization results generated by CPU and
      GPUs. RESULTS: For the BOS case, application of GPUs for the optimization and
      overall gained 54 and 36.5 times speedup. For the prostate case, application of
      GPUs for the optimization and overall gained 69 and 28.5 times speedup.
      CONCLUSIONS: The application of GPUs for the parallel computing of IMPT treatment
      plan optimization can dramatically improve the computation efficiency. The
      optimization time can be reduced from typically half to one hour to only several
      minutes.

PMID- 28519617
TI  - WE-G-BRA-05: Simulated Troubleshooting Session for Medical Physics Resident
      Rotations.
AB  - PURPOSE: Troubleshooting is a difficult to train, but critical skill for a
      clinical medical physicist. It is unlikely that residents will have opportunities
      to troubleshoot many real clinical scenarios during a typical 3 month rotation.
      The ability to analyze and correct abnormal clinical situations is imperative to
      providing safe radiation therapy care. We have developed a novel strategy to
      train medical physics residents to gain such important clinical physics skill.
      METHODS: Simulated troubleshooting sessions were designed for each rotation,
      featuring problematic clinical scenarios. The resident was required to
      troubleshoot each scenario in a given time frame. Using a brachytherapy rotation
      as an example, the transfer tubes connecting the afterloader to the Tandem and
      Ovoids (T&O) applicators were purposely inserted incorrectly. The resident was
      asked to deliver a dummy T&O plan in a reasonable time frame including
      troubleshooting all problems that may occur. Many simulated troubleshooting
      situations were presented to the resident. Two residents went through a 3 month
      brachytherapy rotation, one with and the other without the simulated
      troubleshooting session. All other rotation activities were the same. At the end
      of the rotation, an oral exam was given to test how well the residents understood
      the brachytherapy clinical practice. RESULTS: Both residents were able to pass
      the exam. However, the resident that received the troubleshooting session
      performed better''''a superior understanding of the reasons behind the clinical
      practice and better troubleshooting skills were demonstrated. CONCLUSIONS: To
      train residents to better handle the clinical situations, it is important to
      include a simulated troubleshooting session into clinical rotations. Simulated
      troubleshooting sessions are excellent and necessary supplements to the clinical
      rotations for the residents to gain practical clinical skills.

PMID- 28519618
TI  - WE-G-217BCD-01: BEST IN PHYSICS (IMAGING) - High-Quality CT Imaging in the
      Presence of Surgical Instrumentation Using Spectral System Models and Knowledge
      of Implanted Devices.
AB  - PURPOSE: Imaging in the presence of implants (instrumentation and prostheses)
      presents a notoriously difficult challenge to CT because of photon starvation and
      beam hardening. To alleviate these limitations, a statistical reconstruction
      approach that includes knowledge of implant shape and composition was previously
      reported. This work extends the approach to modeling of photon transport,
      including polychromatic x-ray beams and scatter, and evaluates the method in
      simulated and real data. METHODS: Previous work on Known-Component Reconstruction
      (KCR) is first extended to include a polyenergetic beam (KCR-POLY). The method
      simultaneously estimates the unknown background volume and the position of
      implants with known attenuation and shape. Simulations included an
      anthropomorphic knee with a Co-Cr-Mo implant and system model for an extremities
      CT system (110 kVp+0.2 mm Cu). Experimental validation was performed on an
      imaging bench in which a Titanium spine fixation rod (65 mm long, 5.5 mm
      diameter) was imaged within a 20.5 cm diameter water cylinder (120 kVp+0.2 mm Cu)
      in geometry simulating an interventional C- arm. RESULTS: The polyenergetic
      system model was essential to high image quality in KCR reconstructions of large,
      highly attenuating implants such as knee prostheses and spine instrumentation,
      where standard penalized- likelihood and monoenergetic variants of KCR fail. The
      first application of KCR-POLY in real data demonstrates the potential of the
      algorithm in practice, reducing or eliminating artifacts and restoring image
      uniformity. CONCLUSIONS: The KCR-POLY algorithm yielded major reduction in metal
      artifacts, owing both to a priori component knowledge (the implant) and account
      of the polyenergetic beam, object attenuation, and x-ray scatter. Ongoing
      research focuses on improvements to the registration algorithm, scatter, and
      experimental studies with complex, deformable implants. The work supports
      application of CT to a range of applications conventionally prohibited by metal
      implants - e.g. surgical guidance or diagnostic imaging of joints with
      prostheses. This work was supported in part by NIH 2R01-CA-112163.

PMID- 28519619
TI  - WE-G-217A-03: Respiratory-Related External/Internal Motion Based MR Image
      Reconstruction Using Dynamic Keyhole for Real-Time Tumor Monitoring.
AB  - PURPOSE: It is aim to test the hypothesis that a dynamic keyhole MRI
      reconstruction technique using external/internal respiratory surrogate position
      reduces acquisition time while retaining image quality for real-time tumor
      monitoring, compared to the conventional keyhole technique. METHODS: 46 thoracic
      MRI studies with 13 healthy human subjects have been acquired using a 3T GE MRI.
      Acquired MR images were reconstructed using zero-filling, conventional keyhole
      and the proposed respiratory motion based dynamic keyhole techniques; resultant
      images were then compared for image quality. Undersampled k-space rate in the
      phase encoding direction was determined based on the difference between the
      original image and the reconstructed image. The position of abdominal muscles and
      diaphragm were used to determine any excess data that exists in the overlaid
      temporal data. In addition, the feasibility of the dynamic keyhole method was
      applied using lung tumor MR images. RESULTS: The result from dynamic keyhole
      using respiratory motion demonstrated significant improvement compared with the
      zero-filling and conventional keyhole methods. Firstly, the dynamic keyhole
      method using external respiratory motion had an overlaid average of 79.7% (204
      lines) of 256 lines from 46 datasets, compared to 63.9% in zero-filling and 74.3%
      in conventional keyhole. Secondly, dynamic keyhole method using internal
      diaphragm motion had an overlaid average of 84.5% (216 lines) of 256 lines from
      all datasets compared to 67.1% and 77.8% or zero-filling and conventional
      keyhole, respectively. Lastly, dynamic keyhole has been validated with one
      dataset involving lung tumor MR images. Image blurring artifacts and inferior
      resolution were not present in the final MR images using dynamic keyhole.
      CONCLUSIONS: Dynamic keyhole method using respiratory external/internal surrogate
      motion has been proposed to reconstruct MR images without image artifacts and
      with superior resolution. This method is applicable to MR images targeting lungs
      and other organs affected by respiratory motion for real-time tumor motion
      monitoring.

PMID- 28519620
TI  - WE-G-213CD-03: A Dual Complementary Verification Method for Dynamic Tumor
      Tracking on Vero SBRT.
AB  - PURPOSE: to use complementary cine EPID and gimbals log file analysis for in-vivo
      tracking accuracy monitoring. METHODS: A clinical prototype of dynamic tracking
      (DT) was installed on the Vero SBRT system. This prototype version allowed tumor
      tracking by gimballed linac rotations using an internal-external correspondence
      model. The DT prototype software allowed the detailed logging of all applied
      gimbals rotations during tracking. The integration of an EPID on the vero system
      allowed the acquisition of cine EPID images during DT. We quantified the tracking
      error on cine EPID (E-EPID) by subtracting the target center (fiducial marker
      detection) and the field centroid. Dynamic gimbals log file information was
      combined with orthogonal x-ray verification images to calculate the in-vivo
      tracking error (E-kVLog). The correlation between E-kVLog and E-EPID was
      calculated for validation of the gimbals log file. Further, we investigated the
      sensitivity of the log file tracking error by introducing predefined systematic
      tracking errors. As an application we calculate gimbals log file tracking error
      for dynamic hidden target tests to investigate gravity effects and decoupled
      gimbals rotation from gantry rotation. Finally, calculating complementary cine
      EPID and log file tracking errors evaluated the clinical accuracy of dynamic
      tracking. RESULTS: A strong correlation was found between log file and cine EPID
      tracking error distribution during concurrent measurements (R=0.98). We found
      sensitivity in the gimbals log files to detect a systematic tracking error up to
      0.5 mm. Dynamic hidden target tests showed no gravity influence on tracking
      performance and high degree of decoupled gimbals and gantry rotation during
      dynamic arc dynamic tracking. A submillimetric agreement between clinical
      complementary tracking error measurements was found. CONCLUSIONS: Redundancy of
      the internal gimbals log file with x-ray verification images with complementary
      independent cine EPID images was implemented to monitor the accuracy of gimballed
      tumor tracking on Vero SBRT. Research was financially supported by the Flemish
      government (FWO), Hercules Foundation and BrainLAB AG.

PMID- 28519621
TI  - WE-G-217BCD-07: Implementation and Evaluation of Helical On-Board CBCT and Exact
      Image Reconstruction.
AB  - PURPOSE: Longitudinal coverage of CBCT, which is 17 cm for head scan and 15.5 cm
      for body scan, is not enough to cover the entire PTV for over 90% of head/neck
      and gastrointestinal/genitourinary/gynecologic patients if lymph nodes are
      involved. Helical CBCT, which was accomplished using external beam LINAC in its
      research mode, is one promising way to extend the CBCT longitudinal coverage. Aim
      of this study is to compare Katsevich's exact algorithm with traditional FDK
      algorithm for helical CBCT image reconstruction. METHODS: CBCT projection raw
      data were acquired on a TrueBeam LINAC machine (Varian Medical Systems) in the
      research mode in helical trajectories that encompass a 360 degree rotation, 25 cm
      pitch, 100 kVp, 80 mA, and 25 ms, with a Catphan 600. Reconstruction was done
      with Katsevich's exact and FDK approximate algorithms. Scatter correction, beam
      hardening correction, and non-uniform gantry angle correction, are performed on
      projection data to reduce artifacts and noise. Image qualities (CT number
      accuracy, uniformity, SNR) were evaluated and compared between the reconstruction
      algorithms. RESULTS: Images reconstructed by Katsevich's algorithm show better
      qualities, compared to ones by FDK algorithm and HU numbers have higher
      uniformity and accuracy. The HU-density calibration curve closely conforms to the
      manufacturer recommended values. The level of noise computed as the standard
      deviation in the phantom uniform region is 28.07 for the Katsevich algorithm,
      compared to 44.64 for the FDK algorithm. CONCLUSIONS: Katsevich's exact
      reconstruction algorithm provided better image qualities than FDK for helical
      CBCT scans. This result will very useful for our ongoing investigation of helical
      CBCT, which would lead to improvement of CBCT longitudinal coverage of PTV and
      would be essential for future image-guided adaptive radiation therapy
      applications. Varian Research Agreement with Washington University in St. Louis.

PMID- 28519623
TI  - WE-G-217A-07: Increased MR Spatial Accuracy with Improved Gradient Nonlinearity
      and Magnet Inhomogeneity Correction.
AB  - PURPOSE: To develop improved distortion correction of MR images based on higher
      degree spherical harmonic models of the gradient system and the main magnetic
      field. METHODS: The induced field gradient along all three axes can be modeled by
      first order spherical harmonics. These models provide a true encoding of the
      physical location of a spin to the frequency at which it is detected. Currently
      on many commercial systems, only the lower 5 degrees of the model are used for
      gradient nonlinearity correction. While this provides sufficient accuracy for
      diagnostic imaging, the gradient nonlinearity correction was extended to include
      all first order harmonics up to the 9th degree to improve the spatial accuracy of
      the images. Using zeroth degree spherical harmonics up to the 20th order, a model
      of the main magnetic field was also incorporated into the correction algorithm.
      Shifts caused by field inhomogeneity were calculated using knowledge of the
      receiver bandwidth, frequency encode direction, and the magnetic field at any
      given point. These corrections were applied to images of a 50 cm diameter
      phantom, acquired with an extended FOV 3D FGRE sequence. Any improvements in
      spatial accuracy were measured in the resulting images. RESULTS: Visual
      improvements in spatial accuracy were observed with both corrections. With
      standard gradient nonlinearity correction, edges of the phantom were distorted in
      a wave-like fashion. With accurate models, almost all of the errors at the edges
      of the phantom were corrected when both gradient and field homogeneity
      corrections were applied. CONCLUSION: With accurate models of the gradient and
      magnetic field, the two greatest system-induced spatial errors can be corrected.
      This improved spatial accuracy enables the use of widebore MR scanners for
      therapy planning on large FOV images and guidance of percutaneous devices.
      Further applications include extended FOV imaging for combined PET-MR systems.
      All authors are employed by General Electric Healthcare.

PMID- 28519622
TI  - WE-G-BRCD-04: Development of Automated Determination Method of Robust Beam
      Directions against Patient Setup Errors Based on Spatial Distribution of Electron
      Density in Particle Therapy.
AB  - PURPOSE: The three-dimensional (3D) dose distribution covering a tumor region
      tends to be more breakable if the beam's eye view (BEV) of the 3D electron
      density (ED) map in a beam direction changes more abruptly with large
      fluctuations. Our aim of this study was to develop an automated determination
      method of robust beam directions against the patient setup error based on the ED
      based BEV in the beam direction in the particle therapy. METHODS: The basic idea
      of our proposed method was to find the robust beam directions, whose the ED-based
      BEV has the spatial fluctuations with low special frequency and small amplitude.
      For evaluation of the spatial fluctuation in the ED-based BEV in a beam
      direction, we obtained power spectra of the ED-based BEVs in all directions,
      i.e., 0 to 355 degree, with an interval of 5 degree. It was assumed that as the
      average spatial frequency and amplitude of the fluctuation in the ED-based BEV in
      a beam direction is lower and smaller, respectively, the absolute value of a
      gradient of the power spectrum becomes larger. Therefore the gradient of the
      power spectrum was calculated for determination of the robust beam direction. The
      ED-based BEV was produced by projecting a 3D electron density map derived from
      the computed tomography (CT) image from a beam source to the distal end of a
      planning target volume (PTV). Four cases of head and neck cancer patients were
      selected for evaluation of the proposed method. RESULTS: As a preliminary result,
      radiation oncologists agreed with most beam directions, which seem to be robust
      against patient setup errors, suggested by the proposed method. CONCLUSIONS: Our
      proposed method could be feasible to suggest the robust beam directions against
      patient setup errors in hadron particle therapy.

PMID- 28519624
TI  - WE-G-BRB-06: Real-Time Radiation Field Tracking Using Long Scintillating Fibers.
AB  - PURPOSE: To ensure the quality assurance of small field, dynamic radiotherapy, we
      present and validate a radiation tracking system based on long scintillating
      fibers that allows for the real-time measurement of the position and energetic
      fluence of a small incident radiation field. METHOD: We aligned 60 parallel
      scintillating fibers on a thin grooved acrylic slab with a 100-cm source-to
      fibers distance. Both ends of each scintillating fiber were coupled to clear
      optical fibers to enable light collection by a single CCD camera using an f/0.95,
      50 mm focal length lens. Using a small, static photon radiation field of 2*2 cm2
      of a Varian Clinac iX, we changed the interaction position on the prototype using
      the linac treatment couch. The interaction position parallel and perpendicular to
      the scintillating fiber array were deduced using the optical attenuation of the
      scintillating fibers. The energetic fluence of the incident field was calculated
      from the fibers light fluxes, corrected for the position dependent optical
      attenuation and scintillation efficiency. RESULTS: Considering a treatment couch
      positioning error of +/-0.5 mm, the system was able to measure the field position
      with a mean error of 0.1 mm perpendicular and 0.8 mm parallel to the
      scintillating fiber array. The maximum error measured using this setup was of
      0.13 mm perpendicular and 3.2 mm parallel to the scintillating fiber array. The
      energetic fluence was determined with a mean error of 0.5% and a maximum error of
      2.2%. CONCLUSIONS: This work demonstrates the capacity of a long scintillating
      fibers array to detect in real-time both the position and the energetic fluence
      of an incident small radiation field. Such methodology would allow for the real
      time tracking of small field in both photon and particle radiation therapy.

PMID- 28519625
TI  - WE-G-213CD-07: Enhancing Respiratory Motion Prediction Accuracy Using Audiovisual
      (AV) Biofeedback.
AB  - PURPOSE: Prediction of respiratory-related tumor motion is hampered by
      irregularities present in the patient breathing patterns. Audiovisual (AV)
      biofeedback reduces irregularities, thereby producing a less complex breathing
      pattern. The aim of this project is to improve respiratory motion prediction
      accuracy using an AV biofeedback system. METHODS: An AV biofeedback system
      combined with real-time MRI was implemented in this project (4 human subjects
      across 5 studies (one subject had both an initial and follow-up study)). The AV
      biofeedback system consists of external marker positioned on the abdomen of human
      subjects, being tracked using an RPM system (Real-time Position Management,
      Varian) to guide the subject's breathing. Acquired respiratory data has been used
      as input for motion prediction through a dynamic multi-leaf collimator (DMLC)
      simulator developed by Prof. Keall. The prediction algorithm utilized was a
      kernel density estimation-based real-time prediction algorithm. A variety of
      prediction parameters were tested to determine optimum prediction performance.
      Prediction parameters adjusted were the delay time (DT) and training examples
      (TE); the parameters tested here were: DT/TE = 2500/1500, 2500/100, 1000/250,
      500/250; Given that the data sampling rate was kept at 30 Hz, the resultant
      prediction training window lengths were 49.5, 8.25, 3.3 and 3.3seconds
      respectively. RESULTS: The mean difference between measured and predicted data
      for free breathing was 1.98+/-2.32mm; and 0.65+/-0.65mm for when AV biofeedback
      was implemented (reduction of error of 67%). The most accurate prediction results
      were attained using the parameters: DT/TE = 500 ms/250. CONCLUSIONS: This study
      demonstrates the improvement of respiratory motion prediction accuracy when AV
      biofeedback is implemented to produce a more regular breathing pattern.

PMID- 28519626
TI  - WE-G-217BCD-11: A New Phantom to Study Combined Effects of In-Plane (x,y) and Z
      Axis Resolution for 3-D Imaging.
AB  - PURPOSE: The aim of this work is to develop phantoms that can be used to sample
      the radial and 3D properties of a CT image, including in-plane (x,y) and z-axis
      information. The Phantom is amenable to mathematical analysis of the x, y, and z
      axis resolution properties separately and combined. METHODS: A periodic pattern
      of a pair of opposed (30 degrees ) angled ramps is configured to produce a
      waveform profile across the CT image. A perfect CT image (with no loss of
      resolution) of the test object would produce a consistent geometric pattern of
      the intersection of a line with the pair of angled ramps. However, due to the
      finite resolution (x, y and z), the CT waveform profile will not yield the
      perfect profile; rather it will be influenced by slice thickness, and in-plane
      resolution (PSF, MTF), as well as noise limitations, and other sources of non
      uniformity such as beam hardening etc. Various characteristics of the waveform
      profile including, amplitude, frequency, and slope (rate of climb) of the peaks,
      can be studied using mathematical analysis such as the Fourier transform. It will
      be shown how these performance characteristics are encoded in the wave pattern.
      RESULTS: The waveform profiles are visually examined and mathematically analyzed,
      to demonstrate the effect of Slice Thickness (z axis) and changes of In-Plane
      (x,y) Resolution and non-uniformity across the image field; moreover, the
      harmonic analysis of the waveform is used to predict, either the in-plane
      resolution (MTF), or the z-axis MTF when one of the two is already known.
      CONCLUSIONS: The Wave pattern phantom offers a way to consider 3-D imaging
      characteristics of a CT scanner by scanning a single repetitive test object that
      encodes both in-plane resolution and z-axis resolution and also offers a way to
      study non-uniformity effects throughout the CT plane (volume). DJG is a
      consultant to The Phantom Laboratory and Image OWL, Salem, NY. Funding of other
      authors is supplied by Image OWL Salem, NY.

PMID- 28519627
TI  - WE-G-BRCD-08: Virtual Couch Shift (VCS) by Online Plan Re-Optimization for the
      MRI Linear Accelerator.
AB  - PURPOSE: With the MRI accelerator it will be possible to get continuous patient
      anatomy updates, ranging from organ deformation to patient translation. To
      compensate for translations, one can re-optimize the treatment plan based on the
      online MRI images. Consequently, the IMRT optimization system should be fast and
      robust enough to generate daily a clinically acceptable plan to perform this
      'virtual couch shift (VCS)'. METHODS: The system uses a GPU based Monte-Carlo
      dose engine (GPUMCD) for online beamlet generation in a 1.5 T magnetic field and
      a fast inverse dose optimization algorithm (FIDO). For four phantom and two
      clinical cases (cervix and kidney), we generated clinically acceptable plans. The
      given plans are regenerated after a series of x, y, and z translations (up to 34
      mm) of the patient anatomy, without adapting the optimization constraints as used
      during the initial optimization. The differences between the original plan and
      the regenerated plans are evaluated by using the gamma criterion and the relative
      D99 target coverage. RESULTS: The system accurately reproduced the initial dose
      distribution after translating the phantom and patient anatomies. The gamma
      criterion of 2%/2 mm is satisfied for 99.2% all target voxels and for 97.2% for
      all OAR voxels. The relative D99 differences are almost 0.0 with a small standard
      deviation. With current hardware, a 7 beam cervix beamlet generation and IMRT
      optimization takes 141 seconds, the kidney case takes only 14 seconds.
      CONCLUSIONS: We developed a system which is fast and accurate enough to perform a
      VCS by online re-optimization for the MRI accelerator. Currently we are adding
      sequencing to the system. We expect that this method can also be used for
      compensating patient rotations and tissue deformation and with this go towards
      realtime adaptive treatment planning and delivery.

PMID- 28519628
TI  - WE-G-BRA-01: Development of a Web-Based Dosimetry Training Tool for Therapy and
      Dosimetry Education.
AB  - PURPOSE: Training in clinical dosimetry is an important component of radiation
      therapy, dosimetry, and medical physics training programs. Based on our in-house
      treatment planning system, PLanUNC, we are developing and assessing a web-based
      dosimetry teaching tool to augment existing training programs. METHODS: We
      surveyed radiation therapy program directors to assess the need for clinical
      dosimetry training tools. Based on survey results, we are developing a web-based
      dosimetry-training tool consisting of 10 modules containing didactic content
      based on the ASRT curriculum, student assessment, and hands-on treatment planning
      exercises. External content specialists reviewed the self-paced modules for
      accuracy and content validity. Two external dosimetry students were observed as
      they completed three sections, and were interviewed in-depth to evaluate the
      modules. This qualitative analysis combined features of usability testing with
      formative evaluation of instructional products. We revised the modules based on
      these data. Our next phase, quantitative evaluation, will assess the
      effectiveness of the modules, the quality of the interactivity and the degree of
      student engagement when completing the modules. RESULTS: Sixty-four percent of
      program directors indicated they had insufficient local resources for dosimetry
      training, and over 90% indicated interest in web-based training tools as teaching
      supplements. External evaluators indicated module content was appropriate and
      accurate. Students indicated the modules were easy to use with clear and
      understandable content. They were engaged when using the modules and motivated by
      the interactive components. They placed value on the exercises and the feedback
      they received. CONCLUSIONS: Inter-institutional evaluation improves the quality
      and generalizability of instructional modules. Carefully designed online learning
      modules are viewed as effective teaching tools by dosimetry students. The
      clinical dosimetry teaching tool will be made accessible to therapy and dosimetry
      training programs worldwide. This work is supported by NCI grant 5R25-CA134307.

PMID- 28519629
TI  - WE-G-BRCD-01: A Procedure for Efficient Large-Scale Retrospective Clinical
      Studies for Online Adaptive Radiotherapy.
AB  - PURPOSE: Online adaptive radiotherapy (ART) is promising for handling inter
      fraction variations of patient's geometry. Before a clinical implementation of
      this advanced technology, it is necessary to study its potential clinical gains
      and optimal frequencies to be used for various tumor sites. The goal of this work
      is to establish and examine a procedure for efficient large-scale retrospective
      clinical studies for online ART using a GPU-based re-planning platform. METHODS:
      The proposed procedure utilizes an in-house developed GPU-based replanning
      software called SCORE. SCORE starts by applying deformable registration from CT
      to CBCT and correcting CBCT artifacts and intensities. However, the CBCT image
      may not cover the whole treatment region due to the limited field of view. In
      that case, we use deformed CT for replanning and dose calculation. The final
      optimized fractional dose is calculated using the optimized fluence maps and a
      finite size pencil beam model. We also use the deformed CT to calculate the
      delivered fractional dose using the fluence maps from the original plan. The
      delivered fractional dose is compared to the optimized fractional dose to
      estimate the daily gain of replanning. To compare accumulated optimized dose and
      delivered dose, the delivered and optimized doses are mapped back to the original
      CT geometry using the deformation vector fields. RESULTS: We tested this
      procedure using prostate cancer IMRT cases and found that the re-optimized and
      delivered DVHs and dose distributions can be generated in a couple of minutes.
      CONCLUSIONS: We have developed a procedure using a GPU-based replanning software
      to retrospectively study the clinical gains of online ART in an efficient and
      large scale manner.

PMID- 28519630
TI  - WE-G-BRB-03: On the Detectability of Jaw Decalibrations with the DAVID System.
AB  - PURPOSE: To evaluate if the recently described problems with the calibration of
      jaws at Varian linear accelerators can be detected with the DAVID system.
      METHODS: Recently Varian Clinac field size issues resulted in a widespread
      medical device correction notice, stating that incorrect jaw positioning due to
      excessive connector resistances may result in clinically relevant deviations from
      the intended field size. Since field size checks via the light field, separately
      for each administered field segment, are not practicable, it might be helpful to
      know that an independent, permanently active field size surveillance system is
      routinely used in our department since four years. The DAVID system (PTW
      Freiburg, Germany) is a translucent multiwire transmission ionisation chamber,
      placed in the linac accessory holder. Each detection wire of the chamber is
      positioned in theprojection of the midline of the associated MLC leaf pair,
      resulting in a signal proportional to the leaf pair aperture. High lateral
      resolution has been achieved by a deconvolution software (Looe et al, PMB 55,
      2010, 3981- 3992). MLC decalibrations are detected by comparison between measured
      and reference signal profiles. RESULTS: The side wings of the DAVID system signal
      profiles are sensibly influenced by the position of the backup jaw blocks
      limiting the field size in the direction at right angles to the MLC travel
      direction. Systematic variation of the backup jaw positions for several field
      sizes and IMRT plans has revealed high sensitivity of the signal profile side
      wings with respect to jaw decalibrations. CONCLUSIONS: The DAVID system is able
      to detect, without any delay, suddenly appearing jaw decalibrations down to
      positioning errors less than 1mm. Use of the DAVID system provides the
      independent and permanent surveillance of correct field sizes including the
      position of the backup jaws, making checks of light-field congruence for each
      field segment unnecessary.

PMID- 28519632
TI  - WE-G-217A-02: RF Heating of DBS Lead with T/R Head Coil versus T/R Body Coil.
AB  - PURPOSE: To evaluate the difference in RF heating of deep brain stimulator (DBS)
      leads during MRI procedures using head-only transmitting coil versus whole-body
      transmitting coil. METHODS: A DBS lead was inserted into the center of a 3-liter
      head phantom constructed and filled with gel prepared according the
      specifications in ATSM standard 2182. The portion of the lead outside of the head
      phantom was either coiled and fixed to phantom exterior (lead only), similar to
      that in DBS implanting surgery, or connected through an extension cable to an
      IPG, which is set to zero mA output and turned off (lead+Ext.+IPG). Imaging was
      performed on a 1.5T MRI scanner using either a T/R head coil or the built-in T/R
      body coil. Two different scans: 3D MPRAGE (low SAR) and 3D TSE (high SAR) were
      performed. The temperature at the tip of the DBS lead was recorded every 10s
      using a fiber optical probe. RESULTS: For lead only, the maximum temperature
      change (peak-to-peak) was less than 0.1 C with all scans or coils. For
      lead+Ext.+IPG, 0.4 C change was observed with T/R head coil and 0.95 C with T/R
      body coil for 3D MPRAGE (low SAR). However, 18.0 C and 35.3 C changes were
      observed, respectively, for 3D TSE (high SAR). CONCLUSIONS: If the DBS lead is
      NOT connected to the IPG, no substantial difference in RF heating between the use
      of a T/R head coil and body coil transmit was observed. The temperature changes
      were minimal even under high SAR. Such results suggests that DBS MRI may be
      performed safely with transmitting through body coil and receiving through phased
      array surface coils provided ONLY the lead is present which is often the case
      during intra-operative procedures. Since further study is needed, extreme caution
      is advised before extrapolating these results to patient exams.

PMID- 28519631
TI  - WE-G-213CD-09: Quality Assurance of the Surrogate Signal-Based Dynamic Tumor
      Tracking Irradiation with Vero4DRT (MHI-TM2000).
AB  - PURPOSE: To perform the quality assurance for the dynamic tumor-tracking (DTT)
      irradiation with Vero4DRT (MHI-Tm2 000). METHODS: Vero4DRT swings its gimbaled 6
      MV C-band x-ray head along the pan and tilt direction to track a moving tumor.
      Surrogate signal-based DTT system implemented in Vero4DRT was used. Before DTT
      irradiation, the correlation model (4D-model) between motion of the IR markers on
      the abdominal wall and the tumor position was created with synchronously
      monitoring by the IR camera and orthogonal kV x-ray imaging subsystem. During
      beam delivery, the 4D-model predicted the future tumor position from the
      displacement of the IR markers in real-time, and then contentiously transferred
      the corresponding tracking orientation to the gimbaled x-ray head.Water
      equivalent phantoms were set on a 1D motor-driven base with IR markers. A film
      placed at a depth of 10 cm in the phantom was irradiated under the following
      conditions: stationary state, and tracking and non- tracking state for sinusoidal
      patterns. In addition, the geometric accuracy was evaluated using a 3D moving
      phantom and Polaris Spectra for the previously-acquired patient's respiratory
      pattern. RESULTS: Compared to the stationary conditions, reductions in lateral
      distance between 95% doses of the dose profile were 1.2 mm for tracking and 29.6
      mm for non-tracking state for (amplitude [A], period [T]) = (20 mm, 2 s); and 0.2
      mm and 29.4 mm for (A, T) = (20 mm, 4 s); and 0.0 mm and 11.2 mm for (A, T) = (10
      mm, 2 s), respectively. In the geometric accuracy testing, 95th percentile of the
      tracking error was 0.5 mm in left-right, 1.0 mm in superior-inferior, and 0.5 mm
      in anterior-posterior direction. CONCLUSIONS: We demonstrated that Vero4DRT
      substantially reduced the blurring effects on dose distribution with high
      tracking accuracy, and confirmed the safety of the DTT irradiation for a clinical
      application. This research was supported by the Japan Society for the Promotion
      of Science (JSPS) through its Funding Program for World-Leading Innovation R&D on
      Science and Technology (FIRST Program), and sponsored in part by Mitsubishi Heavy
      Industries, Ltd.

PMID- 28519633
TI  - TH-A-BRCD-01: Electron Radiotherapy: Past, Present, and Future.
AB  - PURPOSE: Delivery constraints on monitor units (MUs) are not currently considered
      during optimization of intensity modulated proton therapy (IMPT) planning in our
      treatment planning system (TPS). This may result in differences between the
      delivered and ideally optimized dose distributions. The purpose of this study is
      to develop a deliverable optimization algorithm incorporating MU constraints
      (DOMU) in IMPT treatment planning and evaluate its clinical applicability.
      METHODS: A novel objective formula was incorporated with the limited-memory
      Broyden-Fletcher-Goldfarb-Shannon (L-BFGS) algorithm to directly optimize the
      deliverable IMPT plan with minimum MU constraint (0.005 MUs per spot). Treatment
      plans for a homogeneous phantom were generated for different spot spacings, using
      optimization without MU constraints and post-processing (OMPP) and DOMU. A
      treatment plan for a head-neck cancer patient prescribed to 63 Gy was also
      designed with DOMU using different spot spacings. For all plans, the dose-volume
      histograms (DVHs) were analyzed to evaluate the benefits of the DOMU. RESULTS:
      For the regular shaped homogeneous phantom, only the plan generated by OMPP using
      5mm spacing showed pronounced dose distortion compared to ideally optimized dose.
      Plan using 7mm spacing still produced accepted target coverage. For the patient
      study, plans generated by OMPP using both 5mm and 7mm spacing displayed
      significant dose distortion and unacceptable target coverage. The dose covering
      99% of the target volume was 60.2 Gy and 61.7 Gy for 5mm and 7mm spot spacing
      plans generated by DOMU, an increase of 18.8 Gy and 18.4 Gy compared with plans
      generated by OMPP. The parotid sparing of DOMU generated plans in 5 mm spot
      spacing was significantly better than that in 7 mm spot spacing indicating the
      importance of using smaller spacing to improve the IMPT quality. CONCLUSION: The
      DOMU algorithm, which incorporates the minimum MU constraints into the
      optimization, can reduce the dos distortion caused by post-processing process and
      achieve the optimum delivered dose.

PMID- 28519634
TI  - WE-G-213CD-02: 4D-PET Maximum Intensity Projections Improve Accuracy of Mobile
      Tumor Volume Delineation.
AB  - PURPOSE: To examine the efficacy and accuracy of respiratory-gated positron
      emission tomography (4D-PET) maximum intensity projections (MIPs) in segmenting
      mobile tumor internal target volumes (ITVs) through a phantom study. METHODS: An
      acrylic phantom was used for PET list-mode acquisition, consisting of 11C-filled
      spheres affixed inside a cylinder containing an 18-fluorodeoxyglucose solution.
      The phantom was attached to a robotic arm that underwent 1D motion based on
      clinically-derived patient breathing trajectories. An amplitude-based gating was
      performed on sequential list-mode sub-files of varying signal-to-background
      ratios, and PET-MIPs were generated from the gated images. ITVs were segmented by
      first denoising and deblurring images using a custom post-processing module and
      then applying an absolute SUV threshold. ITV accuracy was assessed using the
      volume recovery fraction (VRF) - the ratio of measured ITV to true volume
      occupied by the moving phantom spheres - which was used to compare PET-MIP,
      ungated PET, and static sphere images. In addition, the effects of tumor
      trajectories, number of gating windows, and margin additions were investigated.
      RESULTS: VRFs of ITVs generated from PET-MIPs were consistently higher than those
      from ungated PET. They also demonstrated a closer agreement to VRFs of static
      spheres (up to 99% similarity vs. 72% for ungated PET), suggesting that tumor
      motion had very little effect on the accuracy of PET-MIP measurements.
      Trajectories with higher amplitude and baseline drift decreased VRF by up to 14%
      for both PET-MIP and ungated PET. Increasing the number of gating windows (up to
      eight windows) resulted in higher VRFs for PET-MIPs without producing excessive
      image noise. PET-MIPs required a smaller margin addition than ungated PET to
      achieve a better overlap with the ground truth ITV. CONCLUSIONS: Compared to
      ungated PET, PET-MIPs are not significantly affected by tumor motion. 4D-PET
      imaging is a promising and viable methodology to better delineate mobile tumor
      volumes.

PMID- 28519635
TI  - WE-G-217BCD-06: Fully Incorporated Scanning Geometry for Improved Accuracy in C
      Arm CBCT Image Reconstruction.
AB  - PURPOSE: The adoption of C-arm cone-beam CT (CBCT) can minimize interruption to
      the interventional workflow. However, C-arm gantry rotation can be susceptible to
      gravity and mechanical instability, therefore resulting images with contamination
      of tilting and wobbling motion. The purpose of this work is to investigate and
      demonstrate potential improvement of C-arm CBCT images by tailoring and applying
      an innovative iterative algorithm that can fully incorporate accurate scanning
      geometry. METHODS: A clinical C-arm CBCT system (Toshiba Infinix-i, Japan) was
      used for collecting projection data of a patient's brain with aneurysm. A mask
      scan was performed before contrast was injected, and a contrast scan was
      performed during continuous contrast feeding. During each scan, 108 projections
      were acquired over a range of approximately 200 degrees within about 4.6 seconds.
      Logarithm subtraction was then carried out view by view to obtain 108 projections
      of virtually only the vasculature. An iterative algorithm, referred to as the ASD
      POCS algorithm, was modified to fully incorporate calibration data characterizing
      the actual scan geometry that deviates from a circular trajectory due to gantry
      tilting and wobbling. We then applied both FDK and ASD-POCS algorithms to
      reconstructing image from the acquired patient data. RESULTS: In FDK
      reconstructions without considering C-arm tilting and wobbling motion, artifacts
      can be observed, which break vessel continuity and compromise image's clinical
      utility. We then performed FDK reconstructions by incorporating the system
      geometry in the back-projection step and obtained improved vessel continuity.
      Finally we applied the ASD- POCS algorithm by incorporating calibration data in
      the forward- and back- projector, and obtained reconstructions with further
      improvement on the recovery of small, secondary vascular branches. CONCLUSIONS:
      Appropriately developed iterative algorithms can improve C-arm CBCT image quality
      by fully incorporating scanning geometry, and can potentially enable spatial
      resolution demanding applications which can be challenging to achieve with the
      FDK algorithm.

PMID- 28519636
TI  - WE-G-BRCD-03: Improvement in Robustness and Delivery Efficiency of Intensity
      Modulated Proton Therapy Using Single-Field Optimization with Energy Absorber.
AB  - PURPOSE: Intensity-modulated proton therapy (IMPT) using multi-field optimization
      (MFO) could generate highly conformal dose distributions but it is more sensitive
      to setup and proton range uncertainties than IMPT using single-field optimization
      (SFO). This work evaluates the effectiveness of SFO treatment plans with the use
      of energy absorbers (EAs) to improve the robustness and delivery efficiency of
      IMPT for head and neck cancers. METHODS: IMPT treatment plans were generated
      using 2-field SFO with an EA in each field (EA-SFO) for four patients with head
      and neck cancers. We compared the plan quality, robustness, and delivery
      efficiency of the EA- SFO plan with a 3-field MFO plan that was used to treat the
      patient. Robustness analysis of each plan was performed to generate two dose
      distributions, consisting of the highest and the lowest possible doses from
      spatial and range perturbations at every voxel. Dosimetric indices and the
      numbers of energy layers required in the EA-SFO and MFO plans were compared.
      RESULTS: All the nominal EA-SFO plans are clinically acceptable. They achieved
      similar levels of target coverage compared to the MFO plans; the differences in
      D95 of the GTV and CTVs between the two plans were within 3.5%. Although some of
      the OARs received higher dose in the EA- SFO plan, they were all within
      tolerance. The EA-SFO plans yielded an average of 38.5% reduction of plan
      sensitivity to uncertainties in the targets and 18.5% overall. The EA-SFO plans
      used an average of 79 (46%) fewer energy layers than the MFO plans, which
      corresponds to nearly 3 minutes shorter delivery time. CONCLUSIONS: The use of
      energy absorber greatly facilitated the design of clinically acceptable SFO
      treatment plans. Compared to MFO, EA-SFO not only improved the robustness to
      setup and range uncertainties, but also reduced the time required for delivery
      and patient QA.

PMID- 28519637
TI  - WE-G-217A-06: Spatial Accuracy Quantification of an MR System.
AB  - PURPOSE: To develop a phantom and measurement protocol for quantifying spatial
      accuracy of an MR imaging system over its entire imaging volume. METHODS: The
      measurement protocol is comprised of a phantom, a set of MR sequence parameters
      for imaging the phantom, and analysis software for calculating spatial errors in
      the acquired phantom images. The phantom covers the entire imaging volume of the
      scanner above the patient table. It consists of layers of tooling foam which does
      not produce any detectable signal on conventional MR images, embedded with a
      matrix of oil capsules to serve as markers. To account for possible spatial
      errors in the construction of the phantom, the phantom was imaged with CT to
      create a gold standard data set. On MR scanners, the phantom is acquired with a
      3D FGRE sequence that covers an extended FOV of 61.44 mm and with bandwidth = +/
      62.5 kHz. Error measurements are performed by detecting markers in the image sets
      and identifying them based on their known locations on the phantom. The spatial
      error of a marker is defined as the difference between its locations on the MR
      and CT image sets. RESULTS: The phantom was constructed and the measurement
      protocol was executed on two different MR scanners. Some markers were located in
      areas of severe field inhomogeneity or gradient nonlinearity, and could not be
      adequately detected for analysis. Maximum errors over concentric spherical
      regions were observed by plotting the error of each marker as a function of their
      distance from isocenter. CONCLUSION: The proposed phantom and protocol can be an
      effective tool for verifying the spatial accuracy of an MR system, which in turn
      can improve the accuracy and confidence of MR guided therapies. Data from this
      protocol may also be used in the development of advanced distortion correction
      algorithms. Employed by General Electric Healthcare.

PMID- 28519638
TI  - WE-G-BRB-05: On the Importance of Fluorescence Within the Stem Effect of
      Scintillation Detectors.
AB  - PURPOSE: To quantify the nature and composition of the light produced in optical
      fibers under different irradiation conditions and evaluate its impact on
      dosimetry. METHODS: Irradiation of a bare PMMA optical fiber (Mitsubishi ESKA
      Premier) was performed using a superficial therapy unit, an Ir-192 HDR
      brachytherapy source, a Co-60 external-beam unit as well as photon and electron
      beams from a linear accelerator. Spectra of the radiation-induced visible light
      in the fiber were acquired and signals were compared as a function of depth and
      irradiation type. Irradiation of a 75 kVp beam from the superficial therapy unit
      was used to isolate the fluorescence spectrum. Isolation of the Cerenkov spectrum
      component was obtained from irradiation of a 15 MeV electron beam at a 45 degree
      angle. Relative composition in fluorescence and Cerenkov of the stem effect light
      has been determined for all irradiations. RESULTS: The total stem effect spectra
      can be represented by a linear superposition of the fluorescence and Cerenkov
      spectra. The fluorescence contribution was shown to strongly differ between the
      superficial therapy unit (99%+/-1%), the Ir-192 HDR source (25%+/-3%) and higher
      energy irradiations (3%+/-2%). Variations within each energy regime (kV, HDR
      brachytherapy and MV) were small at 3% or lower. These were observed for
      irradiations at angle or when the fiber was near the surface. This study suggests
      it is better to calibrate the stem effect of a scintillation detector using the
      same irradiation modality. CONCLUSIONS: Stem effect light was shown to be
      composed of fluorescence and Cerenkov light in different proportions depending on
      the geometry of the experimental setup, nature of the irradiation, and
      irradiation energy. Calibrating detectors separately for fluorescence and
      Cerenkov may lead to better performance of the stem effect removal technique.

PMID- 28519639
TI  - WE-G-213CD-06: Implementation of Real-Time Tumor Tracking Using Robotic Couch.
AB  - PURPOSE: The purpose of this study was to present a novel method for real- time
      tumor tracking using a commercially available robotic treatment couch, and to
      evaluate tumor tracking accuracy. METHODS: Commercially available robotic couches
      are capable of positioning patients with high level of accuracy; however,
      currently there is no provision for compensating tumor motion using these
      systems. Elekta's existing commercial couch (PreciseTM Table) was used without
      changing its design. To establish the real-time couch motion for tracking, a
      novel control system was developed and implemented. The tabletop could be moved
      in horizontal plane (laterally and longitudinally) using two Maxon-24V motors
      with gearbox combination. Vertical motion was obtained using robust 70V-Rockwell
      Automation motor. For vertical motor position sensing, we used Model 755A-Accu-
      Coder encoder. Two Baumer-ITD_01_4mm shaft encoders were used for the lateral and
      longitudinal motions of the couch. Motors were connected to the Advance Motion
      Controls (AMC) amplifiers: for the vertical motion, motor AMC-20A20-INV amplifier
      was used, and two AMC-Z6A8 amplifiers were applied for the lateral and
      longitudinal couch motions. The Galil DMC-4133 controller was connected to
      standard PC computer using USB port. The system had two independent power
      supplies: Galil PSR-12- 24-12A, 24vdc power supply with diodes for controller and
      24vdc motors and amplifiers, and Galil-PS300W72 72vdc power supply for vertical
      motion. Control algorithms were developed for position and velocity adjustment.
      RESULTS: The system was tested for real-time tracking in the range of 50mm in all
      3 directions (superior-inferior, lateral, anterior- posterior). Accuracies were
      0.15, 0.20, and 0.18mm, respectively. Repeatability of the desired motion was
      within +/- 0.2mm. CONCLUSIONS: Experimental results of couch tracking show
      feasibility of real-time tumor tracking with high level of accuracy (within sub
      millimeter range). This tracking technique potentially offers a simple and
      effective method to minimize healthy tissues irradiation.Acknowledgement: Study
      supported by Elekta,Ltd. Study supported by Elekta, Ltd.

PMID- 28519640
TI  - WE-G-217BCD-10: Shading Correction in Image Domain for Cone-Beam CT Without Prior
      Information.
AB  - PURPOSE: Cone-beam CT (CBCT) images contain severe shading artifacts mostly due
      to scatter. Many algorithms have been proposed to alleviate this problem by data
      correction on projections. Sophisticated methods have also been designed to
      further improve the image quality when prior patient information is available. In
      this work, we develop a novel algorithm for shading correction directly on CBCT
      images without any prior information. METHODS: In CBCT, projection errors (mostly
      scatter) result in dominant low-frequency shading artifacts in image domain. Due
      to circular scan geometry, these artifacts often show global or local radial
      patterns. We first convert the uncorrected images into the polar coordinate
      system. Median filtering and polynomial fitting are applied on the transformed
      images to accurately estimate the low-frequency bias field of shading angle-by
      angle and slice-by-slice. The estimated bias field is then converted back to the
      Cartesian coordinate system, followed by 3D low-pass filtering to eliminate
      possible high-frequency components. The shading-corrected images are finally
      obtained as the uncorrected volume divided by the shading bias field. RESULTS:
      The proposed algorithm has been evaluated on CBCT images of a pelvis patient and
      a head patient. Within regions of interest, the average CBCT error is reduced
      from around 250 HU to 42 and 38 HU, and the spatial non-uniformity error is
      reduced from above 17.5% to 2.1% and 1.7% for the pelvis and the head patients,
      respectively. As our method suppresses only low-frequency shading artifacts,
      patient anatomy and contrast are well retained in the corrected images of both
      cases. CONCLUSIONS: We propose an effective shading correction algorithm on CBCT
      images, with several advantages compared to existing approaches. The method has a
      high efficiency since it is deterministic and directly operates on the
      reconstructed images. It also requires no prior information, which facilitates
      its clinical use as a standard image correction solution.

PMID- 28519642
TI  - WE-G-218-01: Management of RT Patients with Implanted Cardiac Devices: Updated
      Recommendations?
AB  - : It has been long time since AAPM published TG-34 on cardiac pacemakers of older
      technology, which has been the standard document for clinical use, even today,
      for pacemakers (ICPs) and for defibrillators (ICDs), alike. Management of RT
      patients with recent technology cardiac devices has been widely published in
      literature without the provision of a new comprehensive and concise set of
      recommendations. The various effects of interaction of non-ionizing and ionizing
      radiations with those devices are crucial to be studied and accounted for during
      RT treatment deliveries. Thus, AAPM has formed the new TG-203 to work on this
      issue and provide recommendations to the clinical user for management of patients
      with cardiac devices when receiving RT. It has been numerous postings that we see
      in medical physics list server groups inquiring advices on dealing with these
      devices during patient imaging and radiation treatments. As treatment delivery
      technologies (IMRT, SBRT, dose escalations, proton beams, etc) and ICP/ICD
      technology advance, the need to address the management of patients with such
      devices receiving radiation treatment becomes increasingly important. ICDs offer
      the same functionality as ICPs, but they are also able to deliver a high-voltage
      shock to the heart, if needed. Finally, major discrepancies exist among
      manufacturer recommendations and wide variations exist among radiation therapy
      facilities regarding patient management precautions. LEARNING OBJECTIVES: 1.
      Provide a review on sources of potential malfunctions of modern ICPs and ICDs,
      including malfunction mechanisms from high-LET radiations and transient effects
      attributed to medical imaging procedures for radiotherapy. 2. Provide a review on
      management of radiotherapy patients with cardiac implanted devices. 3. Utilize
      recently available data and computation methods of out-of-field/peripheral dose
      by scattered photons and secondary neutrons in order to assess cumulative doses
      on the ICPs and ICDs, during current treatment deliveries (IMRT, SBRT, proton
      beam therapy, etc). Risk of failure associated with these doses will be
      discussed. 4. Provide recommendations for management of radiotherapy patients
      with implanted cardiac devices including the initial patient evaluation stage,
      dosimetric evaluation to the ICP/ICD during treatment simulation, treatment
      planning and treatment delivery. Recommendations for the final evaluation of the
      integrity and functionality of the device after treatment completion will be
      assessed.

PMID- 28519641
TI  - WE-G-BRCD-07: IMRT Re-Planning by Adjusting Voxel-Based Weighting Factors for
      Adaptive Radiotherapy.
AB  - PURPOSE: Adaptive radiation therapy (ART) can reduce normal tissue toxicity
      and/or improve tumor control through treatment adaptations based on the current
      patient anatomy. Developing an efficient re-planning algorithm is an important
      step for ART. For the re-planning process, manual trial-and-error approach to
      fine-tune planning parameters is a time- consuming and resource-requiring task.
      However, prior information in the original plan, such as dose distribution or
      dose-volume histogram (DVH) can be employed to facilitate the re-planning. The
      goal of this work is to develop a re-planning algorithm that automates voxel
      weighting factor adjustments to generate a plan with close, or possibly better,
      DVH curves compared with original plan. METHODS: Our algorithm iterates the
      following two loops. The inner loop is the traditional fluence map optimization,
      in which we optimize a quadratic objective function penalizing the deviation of
      the dose received by each voxel from its prescribed or threshold dose with a set
      of fixed weighting factors. In outer loop, the weighting factors in the objective
      function for each voxel are heuristically adjusted according to the deviation of
      the DVH curves in the calculated plan from those in the original plan. The
      process is repeated until the result converges, or the maximum iteration step is
      reached. The whole algorithm is implemented on GPU for high efficiency. RESULTS:
      We have tested our algorithm on three 8-field head-and-neck cases. Compared with
      the DVH curves in original plan, the DVH curves in the resulting plan using our
      algorithm with 30 iterations are almost better for every structure. We can finish
      the re-optimization process around 30 seconds. CONCLUSIONS: Adjusting voxel-based
      weighting factors automatically, by comparing the DVH curves, seems to be a
      promising approach to avoid the tedious trial-and-error scheme for ART re
      planning. This work is supported by Varian Medical Systems through a Master
      Research Agreement.

PMID- 28519643
TI  - WE-G-BRB-09: CyberKnife Patient Specific QA Using a 4D Cylindrical Diode Array
      System.
AB  - PURPOSE: To examine and facilitate the feasibility of the ArcCheck cylindrical
      diode array system as a patient specific QA device for CyberKnife radiosurgery
      delivery. METHODS: There is an obvious necessity for CyberKnife robotic
      radiosurgery patient QA procedures for hypofractionated treatment of larger
      planned treatment volumes (PTV), e.g. prostate. This need will increase when the
      future CyberKnife MLC is introduced. The small unflattened CyberKnife fields,
      along with the variation of beam-to-detector spatial angles, pose a significant
      detection challenge for dosimetric systems. The feasibility of the ArcCheck (Sun
      Nuclear Inc.) cylindrical diode array system for patient-specific QA on the
      CyberKnife is demonstrated using a beam-to-diode specific angular correction that
      was developed and has been applied. For localization and tracking, four gold seed
      fiducial markers were embedded in the system's central plug. We used a Monte
      Carlo 1% uncertainty for the dose calculation. RESULTS: By disabling the Linac
      based corrections and applying the custom CyberKnife correction that we
      developed, the passing rate increased from 39.6% to 99.8% using a 3%3mm gamma
      criteria for a given lung case. An additional lung case passed 98.5%. In both
      cases, a 10% dose threshold was used. In addition, brain, trigeminal nerve and
      lung cases with synchrony tracking are being investigated. CONCLUSIONS: We
      demonstrated the ArcCheck feasibility for CyberKnife patient specific QA
      performance. The custom CK angular correction that we developed and applied
      showed a high passing rate for the lung cases. A verification of the polar angle
      response should be conducted, in addition to the azimuthal angle that was
      verified for Linacs. Any data that is being retrieved is additional data to the
      current chamber point measurement procedures.

PMID- 28519644
TI  - WE-G-211-03: Development of Ultrasound Imaging Equipment.
AB  - : One of the earliest man-made ultrasound images of the human body was produced
      by Dussik in 1941, when he attempted to image the brain using a through
      transmission technique. These early images were later judged to be artifacts
      related to sound wave transmission through skull bone. Pulse-echo examination of
      the body started in the late 1940's following developments of sonar, radar, and
      ultrasound flaw detectors. Ludwig and colleagues measured speeds of sound in
      tissues, publishing the value 1540 m/s for many tissue paths, a figure still used
      today. Among the pioneering pulse- echo imaging teams in the USA were Wild and
      Reid who developed real time imaging of the breast in the early 1950's, and Howry
      and Bliss, who were able to generate detailed anatomical pictures of the neck by
      employing water bath scanners. Many other groups, including from Japan,
      Australia, and Europe were pursuing both A-scope and B-scope applications of
      ultrasound around this time. Notable achievements include work by Ian Donald in
      the UK, who in 1955 described a contact scanner and published B-scope images
      depicting a variety of anatomical regions. The systems of Donald and of Wild are
      said to have inspired engineers from Howry's water bath team in Colorado to
      develop their own contact scanner, and in 1963 a new company, Physionics produced
      the first commercial, single element transducer "articulated arm" scanner. It
      provided bi-stable B-mode images on a storage oscilloscope, marking the beginning
      of widespread acceptance of this modality. Gradual instrument improvements
      include analog then digital scan converters for gray scale in the 70's, and both
      auxiliary and stand alone mechanical scanning real time probes. Phased array
      technology also emerged for cardiac imaging, as did linear arrays for obstetrics
      and abdominal imaging. Perhaps the most revolutionary instrument ever was
      produced in the early 1980's, the Acuson 128, introducing high image quality
      linear and phased array beamformed images for radiology applications and helping
      to conclude the brief era of manual scanners. As beamformers became digital
      devices in the 1990's, unprecedented image quality, diagnostic features, two
      dimensional arrays, and even system miniaturization evolved, bringing ultrasound
      imaging to its present state. The ultrasound field is still characterized by
      novel instruments emerging from the laboratories of clever scientists, addressing
      diagnostic and therapeutic needs not provided by present day technology. LEARNING
      OBJECTIVES: 1. Describe features of the first commercially available ultrasound
      scanners. 2. Identify the relationship between technological developments in
      radar and emergence of ultrasound as a modality 3. Explain the significance of a
      high large channel count in beamforming 4. Contrast echo acquisition and
      processing in a modern scanner with first generation devices.

PMID- 28519645
TI  - WE-G-BRB-02: MU-EPID an EPID Based Tool for IMRT Quality Assurance.
AB  - PURPOSE: A software program (MU-EPID) has been developed to perform patient
      specific IMRT pre-treatment QA verification using an electronic portal imaging
      device. METHODS: The software converts measured images of intensity modulated
      beams delivered to an EPID, into fluence maps that can be imported in the
      treatment planning system. The dose can then be calculated in the patient anatomy
      and compared against the patient's treatment plan for QA purposes. We first
      benchmarked the software using as a patient a cylindrical phantom. An aSi-1000
      EPID mounted on a Varian Novalis linear accelerator was used for the image
      acquisition. Finally, IMRT plans from different treatment sites were used to
      further validate this in- house software. QA analysis was performed by evaluation
      of isodose distributions, DVH comparison and 2D gamma analysis. RESULTS: The
      validation study with the cylindrical phantom showed that the dose to the ion
      chamber measurement point was in good agreement with both the original treatment
      plan and the MU-EPID reconstructed dose. Similar results were found for the
      clinical cases that we studied. A gamma analysis of the dose to the isocenter
      plane was performed for each plan. Using 3% and 3 mm as the evaluation criteria,
      resulted in an average of 97.44% of pixels passing the analysis (gamma<1). Good
      agreement was also observed for the DVH, isodose and profile comparisons between
      the clinically delivered IMRT plan and the MU-EPID derived dose calculation.
      CONCLUSIONS: The results of the present investigation suggest that MU-EPID can be
      used in a clinical environment and can be used for patient specific QA for IMRT
      plans. This work has been supported by the SCOA.

PMID- 28519646
TI  - WE-G-BRA-04: The Development of a Virtual Reality Dosimetry Training Platform for
      Physics Training.
AB  - PURPOSE: Recently there has been a great deal of interest in the application of
      Simulation methodologies for training. We have previously developed a Virtual
      Environment for Radiotherapy Training, VERT, which simulates a fully interactive
      and functional Linac. Patient and plan data can be accessed across a DICOM
      interface, allowing the treatment process to be simulated. Here we present a
      newly developed range of Physics equipment, which allows the user to undertake
      realistic QC processes. Five devices are available: 1) scanning water phantom, 2)
      'solid water' QC block/ion chamber, 3) light/ radiation field coincidence
      phantom, 4) laser alignment phantom and 5) water based calibration phantom with
      reference class and 'departmental' ion chamber. METHODS: The devices were created
      to operate realistically and function as expected, each has an associated control
      screen which provides control and feedback information. The dosimetric devices
      respond appropriately to the beam qualities available on the Linac. Geometrical
      characteristics of the Linac, e.g. isocentre integrity, laser calibration and jaw
      calibrations can have random errors introduced in order to enable the user learn
      and observe fault conditions. In the calibration module appropriate factors for
      temperature and pressure must be set to correct for ambient, simulated, room
      conditions. RESULTS: The dosimetric devices can be used to characterise the Linac
      beams. Depth doses with Dmax of 15mm/29mm and d10 of 67%/77% respectively for
      10cm square 6/15MV beams were measured. The Quality Indices (TPR20/10 ratios) can
      be measured as 0.668 and 0.761 respectively. CONCLUSIONS: At a simple level the
      tools can be used to demonstrate beam divergence or the effect of the inverse
      square law; They are also designed to be used to simulate the calibration of a
      new ion chamber. We have developed a novel set of tools that allow education of
      Physics processes via simulation training in our virtual environment. Both
      Authors are Founders and Directors of Vertual Ltd, a spin-out company that exists
      to commericalise the results of the research work presented in this abstract.

PMID- 28519647
TI  - WE-G-217A-01: Fast Recovery Driven Equilibrium with Automated Switching to Avoid
      Artifacts.
AB  - PURPOSE: To reduce image artifacts from the unnecessary use of driven-
      equilibrium. Driven-equilibrium methods known as fast recovery, RESTORE, or DRIVE
      enable reduction of repetition time (TR) and hence acquisition time in RARE (FSE
      or TSE) imaging by applying additional RF pulses following each echotrain to
      accelerate T1 recovery. Fast recovery (FR) techniques are most useful when TR is
      less than 4*T1. For neuroimaging, the benefit of FR diminishes as TR increases
      beyond ~3s. In regions of rapid susceptibility change such as near metallic
      implants, FR techniques can introduce artifact because the magnetization is not
      properly rephased when the FR pulses are applied. In our clinical practice we
      observe that technologists frequently adjust TR over a range of 2-5s on a patient
      specific basis to minimize scan time. We do not observe, however, that
      technologists reliably disable FR when TR is long enough, introducing possible
      artifacts. METHODS: An FR-FSE pulse sequence was modified to automatically
      disable the FR feature whenever TR exceeded a user-defined threshold (TR0). Under
      IRB approval, a healthy volunteer was scanned with the sequence using TRs ranging
      from 1-5s, and TR0=900ms or 6s. Contrast- to-noise measurements were made between
      CSF, gray matter and white matter for each dataset. RESULTS: The volunteer study
      shows decreasing benefit of FR as TRs increase beyond 3s. A patient with
      bilateral auditory brainstem implants scanned with and without FR demonstrates FR
      induced artifacts. CONCLUSIONS: We demonstrate an FR-FSE pulse sequence that
      automatically disables fast-recovery whenever TR exceeds an operator- selected
      threshold. The pulse sequence avoids unnecessary artifacts in regions of rapid
      susceptibility changes, while retaining the advantages of FR when TR<TR0.
      Clinical images from a patient with bilateral auditory brainstem implants
      demonstrate potential artifacts introduced by FR, and the benefits of
      automatically avoiding unnecessary use of FR.

PMID- 28519648
TI  - WE-G-218-03: Management of RT Patients with Implanted Cardiac Devices: From
      Recommendation to Practical Implementation.
AB  - : Guidelines for the management of patients with an internal cardiac pacemaker
      (ICP) or internal cardiac defibrillator (ICD) referred for radiotherapy exist but
      are outdated, as both ICP and ICD technology and radiation therapy techniques
      have evolved. (ICPs and ICDs are both CIEDs). Furthermore, the clinical practice
      of patient management varies widely and the number of patient with a ICP or ICD
      referred for radiation therapy is increasing. There is thus a clear need for
      updated guidelines, which are currently developed by the new AAPM TG 203.An
      overview of the literature, existing recommendations and dose measurement methods
      has been given the previous speakers of this session. In this presentation, the
      focus will be more on the management aspects. Which questions need to be answered
      to decide if a patient can receive radiation therapy? How can this be weighted
      against e.g. CIED relocation or replacement? It is clear that good communication
      between the patient, the treating cardiologist and radiation therapy department
      is of importance to come to the best multidisciplinary treatment approach. When
      radiotherapy is given, the practical measures that need to be taken should
      preferably be categorised based on the chance on CIED failure combined with the
      consequence for the patient in case of such failure. Thus, an important
      distinction may be made between pacing dependent and pacing independent patients.
      Examples of such risk classifications with corresponding practical implications
      will be presented, including the new Dutch national guideline recently authorised
      by the national cardiology, pacemaker technologists, medical physics and
      radiation oncology societies. LEARNING OBJECTIVES: 1. Understand and list the
      questions that need to be answered to tailor the treatment to the individual
      patient and whom should be involved in this process. 2. Appreciate the reasons
      why only a crude categorisation of risks can be given. 3. Know how to interpret
      new CIED guidelines, their strengths and weaknesses and have sufficient knowledge
      to translate and incorporate these guidelines into your own institution.

PMID- 28519649
TI  - WE-G-213CD-01: 4D Optimization for Scanned Ion Beam Tracking Therapy for Moving
      Tumors.
AB  - PURPOSE: To apply scanned ion radiotherapy to patients with moving tumors, motion
      mitigation approaches are needed. The purpose of the current study was to
      determine whether 4D optimized ion beam tracking therapy could reduce dose to
      critical structures near a moving target while maintaining target dose coverage.
      METHODS: A conjugate gradient minimization algorithm was developed to incorporate
      4D organ motion data in the optimization of scanned ion pencil beam fluences.
      Treatment plans for 3D and 4D optimized carbon beam tracking were prepared using
      an in- house code for a sphere target volume moving in water with a proximal
      avoidance volume. For 1 lung cancer patient, 3D and 4D optimized carbon beam
      tracking treatment plans were designed to provide uniform dose coverage to a
      clinical target volume and minimal dose to the heart. For both the water phantom
      and patient case, 4D dose distributions were calculated. Differences between 3D
      and 4D optimized beam tracking were analyzed using dose colorplanes, dose-volume
      histograms, and dose-volume statistics. RESULTS: For the sphere target, 3D
      optimized beam tracking achieved target dose coverage of (100.0 +/- 0.3)% and a
      mean and maximum avoidance volume dose of 26.1% and 89.4%, respectively. 4D
      optimized beam tracking achieved target dose coverage of (99.9 +/- 0.4)% and a
      mean and maximum avoidance volume dose of 7.7% and 42.2%, respectively. For the
      lung patient, 3D optimized beam tracking achieved target dose coverage of (101.0
      +/- 5.9)% and a mean and maximum heart dose of 7.7%and 103.4%, respectively. 4D
      optimized beam tracking achieved target dose coverage of (100.0 +/- 0.1)% and a
      mean and maximum heart dose of 8.7% and 100.3%, respectively. CONCLUSIONS: 4D
      optimized ion beam tracking therapy may be used to reduce the maximum dose to
      critical structures near a moving target, compared to 3D optimized ion beam
      tracking therapy. Work supported by the Rosalie B. Hite Fellowship, The
      University of Texas M. D. Anderson Cancer Center, Houston, Texas.

PMID- 28519651
TI  - WE-G-217A-05: Automatic Method for RF Coil Assessment in Clinical MRI: A Three
      Dimensional Approach.
AB  - PURPOSE: MRI RF coil assessment is usually evaluated with region-of-interest
      (ROI) analysis from a single 2D phantom image. This simple approach has worked
      well for large volume coils or phased-array coil with large receivers, but not
      the high density phased-array coils characterized by 3D array arrangement of
      their multiple receivers. This abstract proposes a novel approach for
      quantitative coil assessment based on 3D imaging and 3D ROI analysis. METHODS: To
      characterize all receivers of the coil of interest, a large uniform phantom
      (preferably a corresponding anthropometric phantom) and a large 3D geometric
      coverage fully includes the coil sensitivity volume was applied during MR
      imaging. After imaging, data from all receivers were used to reconstruct a
      composite 3D image, and to reconstruct 3D images from each individual receiver,
      leading to a total of N+1 3D image datasets (where N is the number of coil
      channels). IDL programs were developed to automatically perform ROI analysis on
      the composite image and on the individual receiver images. Instead of choosing
      one single 2D slice out of each 3D dataset, the whole 3D dataset was treated as a
      3D image, and 3D ROIs were automatically generated for coil assessment. RESULTS:
      This 3D coil evaluation approach could be applied to all clinical coils including
      quadrature body/head coils, and phased-array coils with 2 to 32 channels. 3D
      sensitivity map could be generated to check receiver function visually. 3D mean
      SNR, max SNR, and uniformity could be obtained from composite and individual
      channel 3D images fully automatically. Coil/receiver performance assessment was
      very fast and straightforward, regardless of the number of receivers of the coil.
      CONCLUSIONS: 3D imaging in combination with 3D automatic ROI analysis is a fast,
      convenient, and less subjective approach for quantitative coil assessment,
      particularly for high density phased-array coils.

PMID- 28519650
TI  - WE-G-217BCD-05: Fiducial Marker-Based Motion Compensation for the Acquisition of
      3D Knee Geometry Under Weight-Bearing Conditions Using a C-Arm CT Scanner.
AB  - PURPOSE: Imaging the knee under realistic load-bearing conditions can be carried
      out in a horizontal plane using a C-arm CT scanner. Human subjects can be scanned
      in a standing position and acquired data successfully reconstructed. However,
      reconstructing this data is a challenge due to significant artifacts that are
      induced due to involuntary motion. Here, we propose motion correction methods in
      2D and 3D. METHODS: Four volunteers were scanned for 8 seconds while squatting
      with ~30 degree flexion. Eight tantalum fiducial markers suitably attached around
      the knee were used to track motion. The marker position in each projection was
      semi- automatically detected. Each marker's static 3D position, which served as a
      reference to correct temporal motion, was estimated by triangulating each
      marker's 2D position from 248 projections using known projection matrices. Motion
      was corrected in 3 ways: 1) 2D projection shifting based on the mean position of
      markers, 2) 2D projection warping using approximate thin- plate splines, 3) 3D
      rigid body warping. RESULTS: The original reconstruction was severely motion
      corrupted which made it impossible to distinguish the boundaries of bones.
      Reconstruction with projection shifting and warping in 2D improved visualization
      of edges of soft tissue as well as bone. A simple numerical metric of residual
      bead deviation from static position was reduced from 3.2mm to 0.4mm. The 2D-based
      methods are inherently limited in that they cannot fully accommodate different 3D
      movements at different depths from the X-ray source. Reconstruction with 3D
      warping shows clearer edges and less streak artifact than the 2D methods.
      CONCLUSIONS: The proposed three motion correction methods effectively reduced
      motion-induced artifacts in the reconstruction and are therefore suitable for
      weight-bearing scanning. Future work includes scanning patients in standing
      position after contrast injection for evaluating the soft tissue structure and
      constructing 3D finite element models for the estimation of joint cartilage
      stress. This study was supported by Center for Biomedical Imaging at Stanford, by
      Siemens AG, Healthcare Sector, and by the Lucas Foundation at Stanford. The
      concepts and contents proposed here are based on research and are not
      commercially available.

PMID- 28519652
TI  - WE-G-BRB-04: BEST IN PHYSICS (THERAPY) - A Novel Multi-Point Plastic
      Scintillation Detector for in Vivo Dosimetry and Quality Assurance in Radiation
      Therapy.
AB  - PURPOSE: To develop a novel multi-point plastic scintillation detector (mPSD)
      capable of accurately measuring dose at multiple positions simultaneously with
      the use of a single optical guide. METHODS: We built a new generation of plastic
      scintillation detectors composed of multiple scintillating elements along a same
      optical transmission line. Three different scintillating fibers were optically
      coupled to a single collecting optical fiber. A primary challenge for this new
      type of detector is that the output signal is a superposition of multiple
      scintillation spectra and contaminating elements. Acquisition with a spectrometry
      setup allows for the implementation of a new hyperspectral approach that accounts
      for each light-emitting component separately, and allows spectral unmixing. The
      mPSD and an ion chamber were irradiated in a water phantom with a 6 MV photon
      beam. Profiles and depth-dose curves were measured and compared between
      detectors. This detector and the corresponding calibration approach were also
      applied to Ir- 192 HDR brachytherapy. RESULTS: Doses measured with the mPSD were
      in good agreement with the ion chamber measurements for external beam
      irradiations. Average relative differences of (2.3+/-1.1)%, (1.6+/-0.4)% and
      (0.32+/-0.19)% were observed for each scintillating element. The mPSD
      measurements tended to be at least as accurate as published measurements from
      single-point PSDs. For the Ir-192 HDR brachytherapy application, the average
      difference between the treatment planning system and the measurements were (4.6+/
      1.0)% per dwell-position and (2.1+/-1.0)% per catheter. The accuracy of each
      scintillating element was shown to depend on light attenuation and on the
      similarity of its scintillation spectrum in comparison to the other light
      emitters. CONCLUSIONS: The feasibility and accuracy of mPSDs using a single
      transmission line was demonstrated. In addition to well-documented advantages of
      single-point PSDs, the multi-point capability of this single-fiber detector makes
      mPSDs a very promising new technique for quality assurance and on-line in vivo
      dosimetry.

PMID- 28519653
TI  - WE-G-213CD-05: Beam's-Eye-View Prostate Motion Detection during Arc Radiotherapy.
AB  - PURPOSE: To track prostate motion during clinical arc radiotherapy using a novel
      statistical motion tracking algorithm in both phantom and patient systems.
      METHODS: For the phantom study, a dynamic phantom with a custom tumor model and
      radiopaque fiducials was used. For the patient study, the clinical data from two
      prostate patients were acquired during volumetric modulated arc therapy (VMAT).
      For each patient, two gold fiducials (X-Mark, 1cm and 2cm in length) were
      implanted in the prostate. A total of 35 fractions with 2-field full arcs were
      delivered. Beam's-eye- view (BEV) images were acquired in cine mode every five
      fractions at a frame rate of 2 fps.The prostate motion was measured by two
      sequential steps: fiducial detection and motion estimation. In the first step, a
      wavelet- based block matching filter was used to suppress the noise and enhance
      the fiducials in the BEV images. A trajectory of detected fiducials was generated
      along the projection angles. Sequentially, the prostate motion was tracked using
      a statistical maximum a posteriori (MAP) algorithm. The 3-D fiducial position was
      estimated by maximizing the probability of displacement of 2-D projections.
      RESULTS: A total of 8,400 BEV images were processed for this study. The phantom
      experiments showed that the baseline accuracy of estimation is 0.69+/-0.56 mm.
      For patient 1, intra- fraction prostate motion was measured to be 0.98+/-0.51 mm
      for all fractions, and individual fraction motion less than 1 mm. For patient 2,
      intra- fraction motion was 1.12+/-0.65 mm for all fractions. However, an
      exceptionally large displacement was measured as 4.9+/-0.74mm in one of the
      fractions. CONCLUSIONS: Prostate motion during arc-therapy can be rigorously
      tracked to an accuracy of one millimeter. This technique is well suited for in
      treatment room target tracking and post-therapy evaluation. Varian Medical
      Systems Inc.

PMID- 28519654
TI  - WE-G-217BCD-09: Calibration of a DRR Algorithm.
AB  - PURPOSE: To calibrate an algorithm for digitally reconstructed radiographs (DRRs)
      such that synthetic projections cast through an object in a fan-beam CT (FBCT)
      optimally match cone-beam CT projections of the same object. METHODS: Our DRR
      algorithm models the transmission of primary photons through an object with a ray
      tracing algorithm that samples the CT at small steps along each source-detector
      pixel path. Sampled CT values are converted to linear attenuation coefficients
      (LACs), scaled by the step-size, and added to a running sum for each detector
      pixel. We made attenuation measurements of materials of known CT number to
      calibrate a CT to LAC conversion function for our FBCT and CBCT systems. DRRs are
      post- processed to reproduce the tube output, source fluence distribution, and
      detector response of the CBCT system. In addition, they are modified to account
      for scatter, beam hardening, and detector veiling glare. Finally, we determined
      CBCT geometry parameters using a specially designed phantom. RESULTS: We analyzed
      the quality of our DRR algorithm by directly comparing synthetic DRRs cast
      through the FBCT of a Catphan(r) phantom with actual CBCT projections of the
      phantom. Line plots comparing the intensity profiles of the DRRs and CBCT
      projections show that uncorrected DRRs do not align perfectly with the
      projections. However, when scatter, beam hardening, and veiling glare are modeled
      there is much closer agreement. Simulations with different geometry phantom
      shapes and sizes recommend a cylindrical phantom 150 mm in diameter.
      Computational times under one second per DRR are achieved using a GPU for a
      simulated 1024*768 pixel detector with a 512*512*281 mm CT volume and 0.5 mm ray
      step-size. CONCLUSIONS: Our DRR algorithm is able to closely reproduce actual
      CBCT projections taken through a test object. It is optimized specifically for
      the FBCT and CBCT systems in our department. Funded in part by NCI grants
      R01CA123299 and P01CA116602. The authors report no conflicts of interest.

PMID- 28519655
TI  - WE-G-BRCD-06: Knowledge-Based Intensity Modulated Radiotherapy (IMRT) Treatment
      Planning for Prostate Cancer.
AB  - PURPOSE: To verify that a knowledge-based approach to intensity modulated
      radiotherapy (IMRT) treatment planning can create clinically acceptable plans of
      higher or comparable dosimetric quality than prior clinically approved plans.
      METHODS: Each case in a database of 140 IMRT prostate plans treated to 54 - 74Gy
      (28-41 fractions) is used as a query case and is compared to the other 139 cases
      in the database (match cases) using a case- similarity algorithm. 2D beam's eye
      view (BEV) projections of the query and match cases anatomies (planning target
      volume (PTV), rectum, bladder, right and left femoral heads) at treatment gantry
      angles are captured. To quantify similarity between the query and match cases,
      mutual information (MI) values of the query vs. match BEVs are averaged over all
      treatment gantry angles. The BEV PTV projections of the best match case,
      identified by the highest average MI value, are deformed to the query's PTV BEVs.
      The deformation maps are applied to deform the match case's fluences to suit the
      query case and further tweaked by running 50-100 iterations (without manual
      intervention) of the Eclipse optimization engine with constraints directly
      imported from the match case. RESULTS: Approximately 84.3% of the bladder and
      rectum dose constraints were achieved for the original plans whereas 86% were
      achieved for the post-optimized plans. On average, the rectum and bladder volume
      receiving 65Gy was smaller for the original plans than the post-optimized plans
      by (4.52+/-30.84) % and (3.44+/-33.55) % respectively. However, the rectum and
      bladder volume receiving 40Gy was smaller for the post optimized plans than the
      original plans by (1.53+/-24.66) % and (3.65+/-24.44) % respectively.
      CONCLUSIONS: The knowledge-based approach produces treatment plans of greater or
      equivalent dosimetric quality to prior clinically approved plans. This work has
      the potential to semi-automatically provide high quality plans while dramatically
      reducing treatment planning time.

PMID- 28519656
TI  - WE-G-217A-09: Phase Imaging Measurement of Static Magnetic Field Homogeneity.
AB  - PURPOSE: The ACR MRI accreditation program requires measurement of the magnetic
      field homogeneity (MFH) in the annual QA. Full implementation of vendor methods
      can be very time consuming and incorporates techniques not available to clinical
      physicists. Conversely, many of the less involved techniques proposed tend to be
      less inaccurate and/or precise. Here, we propose a robust approach to MFH
      analysis using a simple phase mapping acquisition which is a time efficient
      compromise. METHODS: The root mean square (r.m.s.) for MFH measurement is
      commonly used over multiple slices (~24). In regions with high SNR, the MR signal
      can be reasonably assumed Gaussian distributed. Therefore, the standard deviation
      of phase values in ROI is equivalent to the r.m.s. of those. The standard
      deviations of phases in x, y and z are assumed uncorrelated. Thus, only axial,
      sagittal and coronal planes need to be acquired to approximate the MFH as opposed
      to a full 3D acquisition. To investigate this concept, phase images were acquired
      on four 1.5T clinical scanners and one 3.0 clinical scanner (MAGNETOM Espree,
      Siemens Medical Systems, Signa Excite HD 1.5T, and 3.0T GE Healthcare
      Technologies). The manufacturer phantoms were scanned using two echo times
      (delta_TE=TE2-TE1<5ms) using a simple 2D gradient echo acquisition to produce
      phase images. After acquiring phase difference images in three orthogonal planes,
      the standard deviation was calculated in three circular ROIs (Diameter=10, 20 and
      30cm) in each plane, respectively, to estimate the MFH for the effective DSV.
      RESULTS: The MFH values in five scanners using this method were within vendor
      specifications for the DSV. Additionally, the measured MFH values compared
      favorably with vendor planned maintenance records with <0.1 ppm discrepancy.
      CONCLUSIONS: This proposed method may be a reliable and practical for regular MFH
      measurement in QA programs and providing an independent check of the vendor
      measurement.

PMID- 28519657
TI  - Materials Research at Wuhan University of Technology.

PMID- 28519717
TI  - Phytophthora cinnamomi.
AB  - : Phytophthora cinnamomi is one of the most devastating plant pathogens in the
      world. It infects close to 5000 species of plants, including many of importance
      in agriculture, forestry and horticulture. The inadvertent introduction of P.
      cinnamomi into natural ecosystems, including a number of recognized Global
      Biodiversity Hotspots, has had disastrous consequences for the environment and
      the biodiversity of flora and fauna. The genus Phytophthora belongs to the Class
      Oomycetes, a group of fungus-like organisms that initiate plant disease through
      the production of motile zoospores. Disease control is difficult in agricultural
      and forestry situations and even more challenging in natural ecosystems as a
      result of the scale of the problem and the limited range of effective chemical
      inhibitors. The development of sustainable control measures for the future
      management of P. cinnamomi requires a comprehensive understanding of the cellular
      and molecular basis of pathogen development and pathogenicity. The application of
      next-generation sequencing technologies to generate genomic and transcriptomic
      data promises to underpin a new era in P. cinnamomi research and discovery. The
      aim of this review is to integrate bioinformatic analyses of P. cinnamomi
      sequence data with current knowledge of the cellular and molecular basis of P.
      cinnamomi growth, development and plant infection. The goal is to provide a
      framework for future research by highlighting potential pathogenicity genes,
      shedding light on their possible functions and identifying suitable targets for
      future control measures. TAXONOMY: Phytophthora cinnamomi Rands; Kingdom
      Chromista; Phylum Oomycota or Pseudofungi; Class Oomycetes; Order Peronosporales;
      Family Peronosporaceae; genus Phytophthora. HOST RANGE: Infects about 5000
      species of plants, including 4000 Australian native species. Host plants
      important for agriculture and forestry include avocado, chestnut, macadamia, oak,
      peach and pineapple. DISEASE SYMPTOMS: A root pathogen which causes rotting of
      fine and fibrous roots, but which can also cause stem cankers. Root damage may
      inhibit water movement from roots to shoots, leading to dieback of young shoots.
      USEFUL WEBSITES: http://fungidb.org/fungidb/;
      http://genome.jgi.doe.gov/Phyci1/Phyci1.home.html;
      http://www.ncbi.nlm.nih.gov/assembly/GCA_001314365.1;
      http://www.ncbi.nlm.nih.gov/assembly/GCA_001314505.1.

PMID- 28519777
TI  - SU-E-J-85: Anthropomorphic Development for Intermodality Deformation Algorithms
      Validation.
AB  - PURPOSE: Radiation therapy is often based on a single treatment plan calculated
      on patient's anatomy at the time of the simulation scan. Deformation algorithms
      offer the possibility to register initial treatment plan on a daily CBCT. This
      way, the planning can be adapted to the evolution of patient anatomy. Validation
      of deformable image registration algorithms (DRA) ideally requires the use of
      phantoms offering some deformation possibilitiesMethods: An anthropomorphic,
      pelvic phantom was built to test volume variation (bladder), deformation of
      contours (prostate) and translation (all organs). Algorithms must be able to
      perform intermodality registration. Therefore, images were acquired for both CT
      and CBCT. The phantom has been created in a way to allow total control of the
      deformation amplitude. Each of the three types of deformations studied were
      realized independently and scanned in a manner to have the same initial and
      deformed images set for each modality. RESULTS: Two algorithm systems were use to
      compare their efficiency; an open-source software, a toolbox for registration
      that offers parameter adjustment and a commercial system with limited control for
      user. The phantom provides us usable images for DRA validation. For a 2 cm mass
      center organ translation, the first one reduced 98% of the distance while the
      other only performed 60%. For a 100 ml volume variation, we get 88% and 62%.
      CONCLUSIONS: Comparison of each intermodal deformation registration performed by
      the two algorithm systems show how control on parameters improves registration
      quality. DRA allow the initial planning adaptation on different deformations
      which occur in human body.

PMID- 28519778
TI  - SU-E-J-95: Towards Optimum Boundary Conditions for Biomechanical Model Based
      Deformable Registration Using Intensity Based Image Matching for Prostate
      Correlative Pathology.
AB  - PURPOSE: Deformable registration of histology to MRI is an essential tool to
      validate in vivo prostate cancer imaging. However, direct registration of
      histology to in vivo MR is prone to error due to geometric differences between
      the tissue sections and the in vivo imaging planes. To increase the accuracy of
      registration, an ex vivo high resolution MRI is acquired to compensate for the
      direct registration difficulties. A novel intensity-based deformable registration
      algorithm based on local variation in image intensities is proposed to register
      the histology to ex vivo MRI of prostatectomy specimens. METHODS: Four sets of ex
      vivo MR and whole mount pathology images from four patients were used to
      investigate and validate the technique. In addition, 9 synthetically deformed ex
      vivo MR images were used. The standard deviation in local windows within the
      images was calculated to generate intermediate images based on both MR and
      histology. The intermediate images were registered using the Drop package
      (Munich, Germany). To further increase the accuracy, a final refinement of the
      registration was performed using Drop with a finer B-spline rid. The registration
      parameters were tuned to achieve a visually acceptable registration. Magnitude of
      Differences (MOD) and Angular Error (AE) were used to validate the synthetic
      data, and the Target Registration Error (TRE) of manually indicated landmarks was
      used for the clinical data. RESULTS: MOD of 0.6mm and AE of 8.3 degrees showed
      the efficacy of using intermediate images, compared to 0.8mm and 10.0 degrees
      achieved with Drop without the intermediate images. The average mean+/-std TRE
      among the four patients was 1.0+/-0.6 mm using the proposed method compared to
      1.6+/-1.1 mm using Elastix (Utrecht, The Netherlands). CONCLUSIONS: An intensity
      based deformable registration algorithm which uses intermediate images was
      evaluated on prostatectomy specimens and synthetically deformed clinical data,
      indicating improvement in overall accuracy and robustness. OICR, Terry Fox
      Ultrasound for Cancer Therapy. Dr. Brock is a Cancer Care Ontario Research Chair
      in Cancer Imaging and has financial interest in deformable registration
      technology through the licensing of Morfeus to RaySearch Laboratories.

PMID- 28519779
TI  - SU-E-J-67: A Potential New Technique to Measure Respiratory Tidal Volume Using
      Optical Surface Imaging: A Geometric and Deformable Phantom Study.
AB  - PURPOSE: To develop a new method for accurate measurement of dynamic respiratory
      tidal volume, we investigate the feasibility of measuring torso volume change
      using optical surface imaging (OSI). METHODS: Based on a validated volume
      conservation theory, the tidal volume is equal to the volume change of the torso
      during quiet respiration (Li et al, PMB, 54:1693, 2009). A clinical OSI system
      was employed to acquire surface images of seven geometric phantoms and two
      'deformable' torso phantoms. The mesh surface images were converted into contours
      for volume calculation using a treatment planning system. For geometric phantoms,
      their volumes under the incomplete surface images were calculated with aid of
      their symmetry. The results were compared with theoretical calculation and water
      containment experiments. For deformable torso phantoms, we created volume
      controlled deformation stages by placing deformable PlayDoh (DPD) materials on
      top of rigid Rando/Thorax phantoms, mimicking respiration-induced torso surface
      elevation and volume change. The volume difference under the surfaces with and
      without the DPD padding was calculated with aid of a common posterior line to
      enclose the region of interest. Three different volumes of DPD padding (>500cc)
      were mounted on the torso phantoms and CT scanned for volume measurements.
      RESULTS: For geometric phantoms, the OSI measured volume had accuracy (+/-1s) of
      0.0%+/-1.6% (vs. geometric volume calculation) and 0.6%+/-3.8% (vs. water
      containment experiment). For deformable torso phantoms, the volume change was
      measured using OSI with an accuracy of 1.5%+/-2.5% against the measured volume
      using CT imaging. Linear regression showed a one-to-one relationship between the
      OSI volumes and CT volumes with a slope of 1.003 (r2=0.999). CONCLUSIONS: The
      optical surface imaging system can accurately measure the volume of geometric
      phantoms and the volume change of deformable torso phantoms. The accuracy is
      about 3% against standard volume measurement methods. Further study on human
      subjects is under investigation. Memorial Sloan-Kettering Cancer Center has a
      reserach agreement with Vision RT, Inc.

PMID- 28519780
TI  - SU-E-J-106: Atlas-Based Segmentation: Evaluation of a Multi-Atlas Approach for
      Lung Cancer.
AB  - PURPOSE: Previous studies have shown atlas-based segmentation using a single best
      matched (SBM) atlas subject can significantly reduce contouring time. A new multi
      atlas approach has been shown to provide greater accuracy than SBM for cancer of
      the head and neck. The goal of this study was to evaluate the multi-atlas
      technique for lung cancer treatment planning. METHODS: An institution's SBRT lung
      atlas containing 82 subjects was utilized for atlas segmentation. Each atlas
      subject contained manually defined contours of the esophagus, cord, heart, left
      lung, right lung, and trachea. CT scans and contours for 16 subjects were
      evaluated. SBM used the one automatically determined best match for segmentation.
      Multi-atlas used multiple automatically determined best matches: 3, 4, and 5,
      respectively. The final segmentation for multi-atlas was generated using Majority
      Vote which comprises the area of overlap for at least half of the individual
      segmentations (2 of 3, 2 of 4, and 3 of 5, respectively). Average Dice Similarity
      Coefficients (DSC) were calculated for each structure to compare against manually
      defined 'gold' standard contours for that subject. Overall percent improvement
      was calculated as the proportion of the error corrected by the method, or %
      difference on 1-DSC. RESULTS: All multi-atlas methods were significantly more
      accurate than SBM (p-value < 0.0005) with average DSC of 0.802 +/- 0.172, 0.809
      +/ 0.163, 0.802 +/- 0.182 respectively for Multi-3, Multi-4, and Multi-5 compared
      to 0.773 +/- 0.187 for SBM. No significant differences existed between the
      different multi-atlas approaches. Overall, Multi-4 showed the greatest
      improvement over SBM with 16% improvement followed by Multi-3 and Multi-5 at 12%.
      CONCLUSIONS: Each multi-atlas approach resulted in significantly more accurate
      contours compared to the SBM. While still requiring some editing, this method for
      segmentation using multiple atlases shows promise for further decreasing the
      contouring time required for lung cancer. MIM Software Inc.

PMID- 28519781
TI  - SU-E-J-78: Enhance Patient Positioning Accuracy with Optically Guided Frameless
      Target Localization Technique for Intracranial Radiation Therapy.
AB  - PURPOSE: To make use of the optical guided frameless stereotactic target
      localization technique to detect the interfraction and intrafraction patient
      positioning errors and correct the patient position for fractional intracranial
      therapy, therefore, to enhance the patient positioning accuracy. METHODS: Four
      patients who underwent fractionated intracranial intensity modulated radiation
      therapy (IMRT) were studied. For each patient, in addition to the thermoplastic
      head mask, frameless array and bite-block were used for patient positioning.
      Optical guided frameless planning was utilized to define the coordinates of the
      isocenter during the treatment planning procedure. In each treatment fraction,
      the patient was first set up by matching the room lasers to the BB markers
      attached on the mask. The optical guided frameless system then captured the
      patient position and reported displacements of the current patient position to
      the planned patient position. These displacements were called interfraction
      errors. The treatment plan was designed to have up to 8 non-coplanar fields. Dose
      delivery of the non-coplanar fields required couch rotation which introduced
      isocenter displacements called intrafraction errors. Population statistics of
      interfraction and intrafraction errors (4 patient, 110 fractions) were
      calculated. The optical guided frameless system monitored the patient positioning
      errors and provided guidance for correction prior to the dose delivery. RESULTS:
      Among all patients and radiation treatment fractions, the overall detected
      interfraction error was 3.6+/-1.3 mm (mean +/-SD) and the intrafraction error was
      1.4+/-0.8 mm. Both types of errors were online corrected with the guidance of
      optical guided frameless system. CONCLUSIONS: Conventional laser guided
      thermoplastic mask patient position for intracranial therapy has interfraction
      and intrafraction errors. The optical guided frameless target localization
      technique allows clinicians to dectect and correct these errors online,
      therefore, to enhance the patient positioning accuracy for intracranial radiation
      therapy.

PMID- 28519782
TI  - SU-E-J-117: Computer-Assisted Verification of Accumulated Dose Distribution
      during the Treatment Time Based on Estimation of Four-Dimensional Dose
      Distribution Using an Electronic Portal Imaging Device.
AB  - PURPOSE: The accumulated dose distributions during the course of radiation
      treatment are substantially important for verifying whether treatment dose
      distributions are produced according to planned dose distributions. The purpose
      of this study was to develop a computer-assisted verification method of
      accumulated dose distribution during the irradiation of a tumor based on
      estimation of four-dimensional (4D) dose distribution using an electronic portal
      imaging device (EPID). METHODS: The 4D 'treatment' computed tomography (CT)
      images during the irradiation were estimated based on affine transformations
      including respiratory motions, which were derived by registration between a
      planning portal dose image and treatment portal dose dynamic image. Planning
      portal dose images were calculated from planning CT images and an algorithm for
      calculation of dose spatial distribution. Treatment portal dose images were
      estimated from EPID dynamic images obtained during a treatment time. The planning
      portal dose images were registered to the treatment portal dose images to obtain
      the affine transformation, which could include respiratory motion in a patient
      body. The CT images at a treatment time were determined by deforming the planning
      CT images using the affine transformation matrix. 4D dose distributions during a
      treatment delivery were obtained by applying a dose calculation algorithm to the
      4D treatment CT images. Finally, accumulated dose distributions during the course
      of radiation treatment were verified with planned dose distributions. RESULTS: We
      applied the proposed method to EPID dynamic images of 2 lung cancer patients, and
      evaluated the difference in accumulated dose distribution between the plan and
      treatment using a gamma evaluation (3mm/3%). The average pass rate for 2 cases
      was 78.2%. CONCLUSIONS: The proposed method can be used for adaptively modifying
      the plan based on the dose discrepancy between the plan and treatment. This work
      was partially supported by Grant-in-Aid for Scientific Research (C) (22611011)
      and Okawa Foundation for Information and Telecommunications.

PMID- 28519783
TI  - SU-E-J-99: Automated Registration Method Based on Multi-Scale Edge Preserving
      Scale Space for PET-CT Scanner.
AB  - PURPOSE: The aiming is to improve the mutual information based registration
      method for PET-CT scanner, which faces the challenges of high computational
      complexity and high likelihood of being trapped into local optima due to an
      absence of spatial information. METHODS: In this work, new multi-scale
      registration framework called EPMR was proposed based upon an edge preserving
      total variation L1 norm (TV-L1) scale space representation. TV-L1 scale space is
      constructed by selecting edges and contours of images according to their size
      rather than the intensity values of the image features. This ensures more
      meaningful spatial information with EPMR framework for MI based registration.
      Furthermore, we design an optimal estimation of the TV-L1 parameter in EPMR
      framework by training and minimizing the transformation offset between the
      registered pairs for automated registration in medical system. We validated our
      EPMR method on multi-modal medical datasets from clinical studies with a combined
      PET/CT scanner. We compared our registration framework with other traditional
      registration approaches. RESULTS: Our experimental results demonstrated that our
      method outperformed other methods in terms of the accuracy and robustness for
      medical images. EPMR can always achieve small offset value, which is more close
      to the ground truth, and the speed can be increased by 10%-14% comparing with
      other method for PET-CT registration under the same condition. Furthermore,
      clinical application by adaptive GTV (gross tumor volume) re-contouring for
      clinical PET/CT image guided radiation therapy throughout the course of
      radiotherapy is also studied, and the overlap between the automatically generated
      contours for CT image and the contours delineated by the oncologist using for
      theplanning system are on an average 90%. CONCLUSIONS: In this work, we presented
      a novel scale space decomposition methodology to improve the traditional scale
      space decomposition and performance of Mutual information based image
      registration for PET-CT scanner.

PMID- 28519784
TI  - SU-E-J-71: Dosimetric Impact of Setup Tolerance for Breast Radiation Therapy with
      3D Surface Imaging.
AB  - PURPOSE: 3D surface image guidance (3D SIG) has been shown to improve patient
      positioning accuracy in the treatment of breast cancer, but limited information
      is available regarding the dosimetric consequences of setup tolerances associated
      with breast radiation therapy techniques. The purpose of this study was to
      determine the magnitude of dose-delivery errors associated with setup tolerances
      of 3 mm/3deg and 5 mm/5deg for set-up and monitoring of whole breast radiation
      treatment using (3D SIG). METHODS: Five test patients were selected for direct
      simulation of the maximum acceptable deviation from reference position for
      tangential beams using field-in-field (FinF) techniques. Dosimetric impact was
      determined by simulating the maximum allowable patient translations and
      rotations, recalculating the dose distribution, and propagating the dosimetric
      error for a full treatment course. For the planned and off-set positions,
      dosimetric consequences were evaluated by examining the plan maximum dose, the
      percent coverage of the prescription dose for the lumpectomy bed, the V20Gy and
      V13Gy percentages for the ipsilateral lung, and the maximum point dose to the
      heart. The results are shown in Table I below. RESULTS: For both 3 mm/3deg and 5
      mm/5deg off-sets in relatively large-breasted patients (> 500 cc) no significant
      change is observed. The ipsilateral lung V20Gy and V13Gy had a maximum increase
      of 5.4% and 5.7%, respectively. Maximum dose to the heart increased by a maximum
      of about 8% for those patients being treated to the left breast. The patient with
      the largest dosimetric impact was relatively small-breasted with a lumpectomy
      cavity in close proximity to the field borders. CONCLUSIONS: As tumor bed
      coverage and ipsilateral lung dose were heavily impacted for the studied
      tolerances, it may be beneficial to utilize an appropriately tighter tolerance in
      patients with breast volume < 500 cc with tumor bed volumes near the periphery of
      the field apertures.

PMID- 28519785
TI  - SU-E-J-110: A Novel Level Set Active Contour Algorithm for Multimodality Joint
      Segmentation/Registration Using the Jensen-Renyi Divergence.
AB  - PURPOSE: To present a novel joint segmentation/registration for multimodality
      image-guided and adaptive radiotherapy. A major challenge to this framework is
      the sensitivity of many segmentation or registration algorithms to noise.
      Presented is a level set active contour based on the Jensen-Renyi (JR) divergence
      to achieve improved noise robustness in a multi-modality imaging space. METHODS:
      To present a novel joint segmentation/registration for multimodality image-guided
      and adaptive radiotherapy. A major challenge to this framework is the sensitivity
      of many segmentation or registration algorithms to noise. Presented is a level
      set active contour based on the Jensen-Renyi (JR) divergence to achieve improved
      noise robustness in a multi-modality imaging space. RESULTS: It was found that JR
      divergence when used for segmentation has an improved robustness to noise
      compared to using mutual information, or other entropy-based metrics. The MI
      metric failed at around 2/3 the noise power than the JR divergence. CONCLUSIONS:
      The JR divergence metric is useful for the task of joint
      segmentation/registration of multimodality images and shows improved results
      compared entropy based metric. The algorithm can be easily modified to
      incorporate non-intensity based images, which would allow applications into multi
      modality and texture analysis.

PMID- 28519786
TI  - SU-E-J-82: Improvement in Reproducibility of Lung Expansion Measures with
      Respiratory Effort Correction.
AB  - PURPOSE: Longitudinal measurements of pulmonary function must account for subject
      variation when assessing radiation-induced changes. Previously, we reported intra
      subject reproducibility of Jacobian-based measures of lung tissue expansion using
      repeat 4DCT scans prior to radiation therapy without correcting for differences
      in respiratory effort. In this study, we present two normalization schemes that
      correct ventilation images for variations in respiratory effort. METHODS: Two
      repeat 4DCT image acquisitions were collected before treatment from seven
      patients. Using a tissue volume preserving deformable image registration
      algorithm, two Jacobian ventilation maps were computed from separate
      acquisitions. Two effort normalization strategies were investigated using
      intermediated inspiration phases upon the principles of equivalent tidal volume
      (ETV) and equivalent lung volume (ELV). Additional experiments were performed to
      verify the effectiveness of the ETV method. Scatter plots of two ventilation maps
      and statistical parameters of Jacobian ratio were compared before and after each
      effort correction approach. RESULTS: The scatter plots of the ventilation maps
      show improvement in measurement reproducibility using either the ETV or ELV
      effort correction for all but one case. The one case that did not show
      improvement had a very similar lung volumes and tidal volumes in the two studies,
      so effort correction was unnecessary. The coefficient of variation (CV) of
      Jacobian ratio improved by 21+/-11 percent (mean+/-standard deviation) after ETV,
      and improved by 20+/-17 percent after ELV. Our experimental results on ETV show
      the decrease of tidal volume difference in two acquisitions improves
      reproducibility of lung expansion measures. CONCLUSIONS: ETV and ELV correction
      methods improve the reproducibility of pulmonary function measurements in
      subjects that have differences in respiratory effort in the baseline and followup
      scans. Additional work is needed to investigate whether ETV or ELV is more
      effective, and to develop alternate regional normalization schemes that can
      account for difference in lung expansion rates.

PMID- 28519787
TI  - SU-E-J-121: A New 4D Radiotherapy Planning Strategy Using Synthesized Tumor
      Motion-Compensated Computed Tomography.
AB  - PURPOSE: To validate a four-dimensional radiotherapy (4DRT) planning based on a
      synthesized CT image compensating for tumor motion, accounting for tumor
      rotation, deformation and distortion due to motion artifacts, and producing
      realistic normal tissue density in motion-tracking beam eye view. METHODS: 4D
      computed tomography (4DCT) images of six patients with peripheral lung lesions in
      mid or lower lobs (motion range: 0.5-3.5cm and size: 1.5+/-2.0 cm3 ) were used. A
      customized program was used for simulating the patient anatomy with a motion
      compensated tumor using 4DCT by aligning the tumor and averaging the 4DCT into a
      static 3.5DCT image. The gross tumor volume (GTV) was delineated
      semiautomatically using a threshold algorithm. Variation of GTV in each phase CT
      was assessed across all phases. 3DRT plans were generated using 3.5DCT and 4DCT
      and compared for validation. An integrated dose volume histogram (iDVH) from all
      phase plans and dose warping using deformable image registration (DIR) were used
      for evaluating 4D plans and comparing with 3.5D plans. RESULTS: The range of
      tumor volume variation over the mean within a breathing cycle was 87%+/-46%. The
      3.5DCT produced an 'averaged' GTV, more reliable than that from any phase CT. The
      results show that the 3.5D plan is equivalent to the 4D plan, except for low dose
      area, using the iDVH evaluation. On average, the percentage difference for the
      areas under the DVH and iDVH is 4.3%+/-2.7%, while 2/3 of the difference results
      from low dose region blow D20%. Using DIR-based dose warping, PTV coverage varies
      due to DIR uncertainty for the small lesions. CONCLUSIONS: The 3.5D plan is
      equivalent to the 4D plan for peripheral lung lesions, yet requires much less
      clinical workload. The 3.5D plan accounts for tumor motion and tumor variation
      for a more reliable delineation, and for realistic normal tissue representation
      for motion tracking.

PMID- 28519788
TI  - SU-E-J-92: CERR: New Tools to Analyze Image Registration Precision.
AB  - PURPOSE: To present new tools in CERR (The Computational Environment for
      Radiotherapy Research) to analyze image registration and other software
      updates/additions. METHODS: CERR continues to be a key environment (cited more
      than 129 times to date) for numerous RT-research studies involving outcomes
      modeling, prototyping algorithms for segmentation, and registration, experiments
      with phantom dosimetry, IMRT research, etc. Image registration is one of the key
      technologies required in many research studies. CERR has been interfaced with
      popular image registration frameworks like Plastimatch and ITK. Once the images
      have been autoregistered, CERR provides tools to analyze the accuracy of
      registration using the following innovative approaches (1)Distance Discordance
      Histograms (DDH), described in detail in a separate paper and (2)'MirrorScope',
      explained as follows: for any view plane the 2-d image is broken up into a 2d
      grid of medium-sized squares. Each square contains a right-half, which is the
      reference image, and a left-half, which is the mirror flipped version of the
      overlay image. The user can increase or decrease the size of this grid to control
      the resolution of the analysis. Other updates to CERR include tools to extract
      image and dosimetric features programmatically and storage in a central database
      and tools to interface with Statistical analysis software like SPSS and Matlab
      Statistics toolbox. RESULTS: MirrorScope was compared on various examples,
      including 'perfect' registration examples and 'artificially translated'
      registrations. for 'perfect' registration, the patterns obtained within each
      circles are symmetric, and are easily, visually recognized as aligned. For
      registrations that are off, the patterns obtained in the circles located in the
      regions of imperfections show unsymmetrical patterns that are easily recognized.
      CONCLUSIONS: The new updates to CERR further increase its utility for RT
      research. Mirrorscope is a visually intuitive method of monitoring the accuracy
      of image registration that improves on the visual confusion of standard methods.

PMID- 28519789
TI  - SU-E-J-103: Characteristics of Bladder Wall Deformation as a Function of Bladder
      Filling.
AB  - PURPOSE: ICRU report 83 recommends delineation of the wall for hollow organs such
      as the bladder. For image guided radiotherapy, there is no guidance as to how to
      delineate deformed walls as the filling of hollow organs change. This work
      investigates characteristics of bladder wall deformation as a function of bladder
      filling in a controlled process. METHODS: CT images of a fresh pig bladder are
      obtained in-air with different bladder air fillings. A plastic hose inserted into
      and glued to the bladder neck forms an air-tight seal for filling with a syringe.
      At each air-filling level, a helical CT (90kV, 90mAs) of the bladder is obtained.
      The pixel size on all CT images is <0.5 mm. Images are imported into a commercial
      planning system for delineation and statistical evaluation. Bladder walls at each
      filling status are auto-contoured, then edited for quality assurance slice by
      slice. The auto-contouring threshold is selected to obtain consistent volumes of
      the resulting region-of-interest at each filling status. RESULTS: When the
      bladder wall interior volume increases by 360 cm3 from injecting air, the wall
      thickness decreases from 2.9 mm to 1.2 mm. The decrease in wall thickness is
      accompanied by a decrease in the wall CT number. CONCLUSIONS: For a pig bladder,
      the wall thickness decreases with increased air filling. The CT number (hence
      apparent density) of the volume decreases as the bladder expands. Further
      investigation is ongoing to determine if the apparent density decrease is real,
      due to CT reconstruction, or due to the bladder being in an air, rather than
      liquid environment. Characterization of hollow organ wall thickness variations
      may be important for image guided radiation therapy and organ wall dose
      evaluation. Support: P01CA116602.

PMID- 28519790
TI  - SU-E-J-63: Feasibility Study of Proton Digital Tomosynthesis in Proton Beam
      Therapy.
AB  - PURPOSE: We investigated the feasibility of proton tomosynthesis as daily
      positioning of patients and compared the results with photon tomosynthesis as an
      alternative to conventional portal imaging or on-board cone-beam computed
      tomography. METHODS: Dedicated photon-like proton beam using the passively
      scattered proton beams by the cyclotron was generated for proton imaging. The
      eleven projections were acquired over 30 degree with 3 degree increment in order
      to investigate the performance of proton tomosynthesis. The cylinder blocks and
      resolution phantom were used to evaluate imaging performance. Resolution phantom
      of a cylinder of diameter 12 cm was used to investigate the reconstructed imaging
      characteristics. Electron density cylinder blocks with diameter of 28 mm and
      height of 70 mm were employed to assess the imaging quality. The solid water,
      breast, bone, adipose, lung, muscle, and liver, which were tissue equivalent
      inserts, were positioned around the resolution phantom. The images were
      reconstructed by projection onto convex sets (POCS) algorithm and total variation
      minimization (TVM) methods. The Gafchromic EBT films were utilized for measuring
      the photon-like proton beams as a proton detector. In addition, the photon
      tomosynthesis images were obtained for a comparison with proton tomosynthesis
      images. The same angular sampling data were acquired for both proton and photon
      tomosynthesis. RESULTS: In the resolution phantom image obtained proton
      tomosynthesis, down to 1.6 mm diameter rods were resolved visually, although the
      separation between adjacent rods was less distinct. In contrast, down to 1.2 mm
      diameter rods were resolved visually in the reconstructed image obtained photon
      tomosynthesis. Both proton and photon tomosynthesis images were similar in
      intensities of different density blocks. CONCLUSIONS: Our results demonstrated
      that proton tomosynthesis could make it possible to provide comparable tomography
      imaging to photon tomosynthesis for positioning as determined by manual
      registration of high density materials.

PMID- 28519791
TI  - SU-E-J-94: Investigating the Use of Deformable Algorithms to Register MR Images
      Acquired with and Without an Endo-Rectal Coil.
AB  - PURPOSE: Magnetic resonance spectroscopic imaging (MRSI) can identify the
      dominant intraprostatic lesion, which can then be boosted using high-dose rate
      (HDR) brachytherapy. MRSI requires the use of an endo-rectal coil, which deforms
      the prostate. We investigate the performance of deformable registration
      algorithms to deform MR images acquired with an endo-rectal coil to images
      acquired without a coil for HDR brachytherapy planning. METHODS: This study
      utilized MR images of five HDR brachytherapy patients acquired with and without
      an endo-rectal coil during the same MRSI imaging study. The prostate was
      contoured on each set of 'Coil-In' and 'Coil-Out' MR images by an experienced
      radiation oncologist. The 'Coil-In' and 'Coil-Out' images were rigidly aligned
      such that the posterior margins of the prostate were as close as possible without
      deformation. Variations on a commercially available deformation algorithm using
      the B-spline method were applied to a volume of interest that surrounded the
      prostate and excluded as much of the coil and rectum as possible. The Dice
      similarity index (DSI) was calculated between rigidly registered contours (DSI1),
      and compared to the DSI calculated between the 'Coil-In' contour and the contour
      deformed from the 'Coil-Out' image to the 'Coil-In' image (DSI2). The difference
      was calculated between DSI2 and DSI1, where a positive change in DSI would
      indicate an improvement in contour agreement over rigid registration of the
      prostate in the 'Coil-Out' and 'Coil-In' images. RESULTS: The B-spline
      deformation algorithm designed specifically for MR images was most effective in
      deforming the 'Coil-Out' to the 'Coil-In' prostate contour with a mean change in
      DSI of 0.0124 with contrast correction, and 0.0004 without. CONCLUSIONS: Out of
      six algorithms tested, only the MR-specific algorithm produced positive changes
      in DSI. The accuracy of the deformation algorithm on mapping the internal
      structures of the prostate between 'Coil-Out' and 'Coil-In' images is under
      investigation. We acknowledge Velocity for providing the registration software.

PMID- 28519792
TI  - SU-E-J-66: Evaluation of Proton Induced X-Ray Fluorescence from Gold Fiducial
      Markers for In-Vivo Determination of Proton Range and Energy.
AB  - PURPOSE: To evaluate a method for in-vivo determination of proton range and post
      Bragg peak straggling by detection of proton induced x-ray fluorescence of
      markers placed at known locations. METHODS: Therapeutic beams from the UF Proton
      Therapy Institute were used to excite proton-induced x-ray fluorescence emission
      (PIXE) from cylindrical pure gold fiducial markers. The markers were embedded in
      a homogeneous water phantom and PIXE was measured using NaI photodetectors with
      energy dispersive spectral analysis. The geometry of the phantom and marker
      placement was chosen to model parallel-opposed beam treatment of prostate cancer
      by proton therapy. The fluorescence yield from these markers was further modeled
      using the GEANT4 Monte-Carlo package with low-energy corrections. Gold K and L
      shell fluorescence yield as determined by the GEANT4 simulations was verified
      quantitatively by comparison to measured Au yield at energies from 1 MeV to 68
      MeV, and to semiempirical model calculations covering the energy range from 1 MeV
      to 15 MeV. RESULTS: The Au K-shell fluorescence cross section is significantly
      smaller thanthat of the L-shell, but the higher yield of the L-shell fluorescence
      isoffset by the larger absorption as the x-ray exits the phantom. The
      overallrelative detection efficiency of K and L shell fluorescence depends on
      thedetails of the shape of the phantom and location of the marker.
      Acharacteristic shape of fluorescence yield as it depends on proton range
      isfound, which can be used to extract an in-vivo PDD profile of a spread-outBragg
      peak (SOBP). CONCLUSIONS: A combination of a specific protocol for delivering a
      SOBP, geometriclocation of fiducial markers from CT, and simultaneous detection
      of protoninduced x-ray fluorescence, can determine the depth range of a primary
      protonbeam in-vivo. The fluorescence yield as measured at the Proton Therapy
      Institute is easily distinguished from background radiation.

PMID- 28519794
TI  - SU-E-J-77: Clinical Evaluation of a Three-Dimensional Optical Surface Based
      Imaging Device for Breast Treatment Setup.
AB  - PURPOSE: The purpose of this work is to evaluate the accuracy of a three
      dimensional surface based optical imaging device for treatment setup of breast
      patients. A commercial system has been used to acquire live surface contour data,
      which are registered with a reference surface contour for setup corrections. This
      work is to investigate the accuracy of this system when compared with
      conventional portal images. METHODS: The system was clinically applied to twenty
      breast cancer patients receiving radiotherapy treatment. For each patient,
      conventional portal imaging before the first fraction was acquired and approved
      by clinicians. After approval of portal images, a reference surface contour was
      acquired. This reference contour was subsequently used to guide daily patient
      setup followed by weekly portal images. A total of 89 sets of portal images were
      acquired for these patients. On days when portal images were taken, optical
      images were used to guide for initial patient setup, then portal images were
      taken and evaluated in order to make direct comparison between the optical
      imaging system and the conventional portal images. RESULTS: Among 89 sets of
      portal images taken after optical imaging guidance, 11 (12%) sets of portal
      images required further adjustments in order to achieve clinically acceptable
      criteria. The average vector adjustments for these 11 fractions were 0.65 cm +/-
      0.30 cm. Average vector shifts made according to the optical imaging for all
      fractions of 20 patients was 0.66 +/- 0.33 cm. CONCLUSIONS: Our data show that
      the commercial optical system can improve the accuracy of treatment setup for
      breast patients without additional radiation exposure. The observed discrepancy
      between the portal images and optimal images requires further investigation. The
      optical imaging guidance can be routinely used between normally scheduled portal
      imaging.

PMID- 28519793
TI  - SU-E-J-105: Evaluating Auto-Contouring of Prostate KV Conebeam CTs.
AB  - PURPOSE: Auto-contouring of daily kV conebeam CTs (kVCBCT) is critical for online
      adaptive radiotherapy. We surveyed a set of geometric and dosimetric measures to
      determine which best assess the suitability of kVCBCT contouring algorithms for
      use in prostate region adaptive planning. METHODS: Six patients with daily kVCBCT
      undergoing IMRT of the prostate to 78 Gy were selected. Dose was recalculated
      with patient density forced to water. Contours were generated on nine kVCBCT for
      each patient using ABAS (Elekta Ltd.) and also by a physician. The prostate mean
      dose, D100, D98, where determined and V70 (% and cc) and mean dose for the
      bladder and rectum for both physician and auto contours. The Dice's Coefficient
      (DC) was calculated between auto and physician contours, as well as a restricted
      DC (rDC) which combines geometric and dosimetric information by comparing only
      the volume within a high dose region. RESULTS: Prostate accuracy can only be
      discerned with D100, additionally there is no correlation (R2=0.036) between D100
      and DC. For all organs, mean dose does not reflect contour suitability. There is
      large variation in V70 (% and cc) for rectum and bladder, implying V70 is a
      sensitive indicator of contour suitability. There is however no correlation of
      V70 with DC. A dose region (>57 Gy) to calculate rDC was chosen to provided
      optimal correlation (R2>0.81) to V70 (% and cc, rectum and bladder). CONCLUSIONS:
      V70 for rectum and bladder shows the most sensitivity to contour suitability, by
      concentrating on where accuracy is most vital. Prostate contouring is less
      critical due to treatment margins, D100 provides the most discerning metric. DC
      and mean dose are not useable. In lieu of V70, rDC could be used. The rDC can be
      approximated by limiting to within 2-3 cm of the prostate contour, alleviating
      the need to calculate dose. A research version of ABAS was provided by Elekta.

PMID- 28519795
TI  - SU-E-J-116: Investigation of Accuracy and Precision of ITV Delineation by PET SUV
      Threshold.
AB  - PURPOSE: To determine PET SUV values in Pinnacle TPS and to assess the accuracy
      and precision of the ITV according to SUV thresholds. The goal is to minimize
      errors in target definition by using SUV showing enhanced metabolic activity of
      the tumor and fast CT imaging with less motion artifacts. METHODS: Mean PET
      values in individual patients were obtained from statistics of body contours for
      whole body PET-CT scans. The SUVs were calculated by normalizing the PET values
      in any voxel by the mean body PET value. These clinically acquired SUVs were
      plotted against values reported at the time of the scan for verification. GTVs
      were contoured on petCT scans and the ITV's were contoured using three published
      methods of SUV thresholds at 2.5, at ratio of 40 percent of the maximum, and 30
      percent of the maximum added to 60 percent of the mean body. GTV volumes were
      plotted against the 3 sets of ITVs to investigate their relationships. RESULTS:
      Examination of 11 patients showed a strong linear relationship between clinically
      determined SUVs and those reported; indicating the validity of our SUV
      definition. Plots of GTV volumes versus ITV volumes for each of the 3 thresholds
      revealed a less clear relationship. The effectiveness of each method to generate
      a reasonable ITV was highly patient dependent; in general the 2.5 threshold gave
      the best results, while the 40 percent maximum produced the worst. CONCLUSIONS:
      While more data is required to make a definitive statement about the value of PET
      SUV threshold defined ITVs, the findings do seem to reveal a pattern between GTV
      and ITV size. If an appropriate SUV threshold is chosen, the GTV-ITV volume
      relationship is nearly linear, which suggests extending the GTV in volume rather
      than the margin distance as is common in ITV delineation.

PMID- 28519796
TI  - SU-E-J-88: Deformable Registration Using Multi-Resolution Demons Algorithm for
      4DCT.
AB  - PURPOSE: In order to register 4DCT efficiently, we propose an improved deformable
      registration algorithm based on improved multi-resolution demons strategy to
      improve the efficiency of the algorithm. METHODS: 4DCT images of lung cancer
      patients are collected from a General Electric Discovery ST CT scanner from our
      cancer hospital. All of the images are sorted into groups and reconstructed
      according to their phases, and eachrespiratory cycle is divided into 10 phases
      with the time interval of 10%. Firstly, in our improved demons algorithm we use
      gradients of both reference and floating images as deformation forces and also
      redistribute the forces according to the proportion of the two forces.
      Furthermore, we introduce intermediate variable to cost function for decreasing
      the noise in registration process. At the same time, Gaussian multi-resolution
      strategy and BFGS method for optimization are used to improve speed and accuracy
      of the registration. To validate the performance of the algorithm, we register
      the previous 10 phase-images. We compared the difference of floating and
      reference images before and after registered where two landmarks are decided by
      experienced clinician. We registered 10 phase-images of 4D-CT which is lung
      cancer patient from cancer hospital and choose images in exhalationas the
      reference images, and all other images were registered into the reference images.
      RESULTS: This method has a good accuracy demonstrated by a higher similarity
      measure for registration of 4D-CT and it can register a large deformation
      precisely. Finally, we obtain the tumor target achieved by the deformation fields
      using proposed method, which is more accurately than the internal margin (IM)
      expanded by the Gross Tumor Volume (GTV). Furthermore, we achieve tumor and
      normal tissue tracking and dose accumulation using 4DCT data. CONCLUSIONS: An
      efficient deformable registration algorithm was proposed by using multi
      resolution demons algorithm for 4DCT.

PMID- 28519797
TI  - SU-E-J-98: 3D Tracking of Interfraction Patient Setup Uncertainties Using
      Multiple Kinect Sensors.
AB  - PURPOSE: On-board optical 3D imaging enables measuring daily setup patient
      uncertainties without involving any additional imaging-induced radiation dose to
      critical structures. We hypothesize that the tumor and normal organ deformation
      caused by routine patient head and neck misalignments can be determined by
      coupling a quantitative patient-specific biomechanical model with quantitative
      skin surface 3D imaging. METHODS: A set of 3D cameras are used to track the
      patient anatomy externally. One of the cameras employed a marker less face
      recognition and tracking for delineating the region of the patient's face. The
      location of the face was then shared among the camera controllers in real-time
      and the anatomical contour that closely matches the face region is selected and
      integrated to form a single 3D anatomical representation. Patient surface
      aligning was performed between the patient's external surface obtained from a
      reference 3D anatomy (simulation CT, MRI, patient surface map from previous
      fraction) and the above-mentioned camera system to quantify the daily patient
      setup variations. For each of the 3D patient surface, a point feature histogram
      (PFH) was first generated. Once the PFH descriptors were generated, a non-rigid
      iterative closest point registration algorithm that minimizes the difference in
      the PFH descriptor aligns the patient surface to the reference 3D anatomy.
      RESULTS: The proposed tracking system was able to track both the patient surface
      setup uncertainty and the internal anatomy when coupledwith a patient specific
      biomechanical head and neck model. CONCLUSIONS: A 3D head and neck tracking
      system that monitors the interfraction patient setup uncertainties in the head
      and neck cancer patient is presented. The aligning process was shown to perform
      for cases with and without the head immobilization system. The external patient
      surface manifold and the motion vectors will be coupled to align the
      biomechanical model using model-guided techniques.

PMID- 28519798
TI  - SU-E-J-70: A Study of the Correlation of 3D Surface Matching and KV Imaging for
      Chestwall IMRT.
AB  - PURPOSE: We investigated the accuracy of surface matching compared to kV
      positioning of 10 post-mastectomy chestwall patients receiving inverse-planned,
      non-gated IMRT. METHODS: During 130 treatment sessions, non-gated 3D surfaces
      were captured using AlignRT (v4.5) before and after table translations as
      indicated by kV imaging. Surfaces were compared to a reference generated from CT
      data. Pearson's correlations between 'indicated' AlignRT and kV shifts were
      studied for surface registration of user-defined regions-of-interest (ROIs): the
      entire surface ('all') and the chestwall ('cw'). In 21% of sessions, two
      consecutive surfaces of patients in identical positions were used to estimate
      variability. Finally, the 'implemented' shifts detected by AlignRT were
      calculated and compared to the absolute table translations. RESULTS: Correlations
      between 'indicated' AlignRT and kV shifts were higher for 'cw' than for 'all':
      r=0.65 (Anterior-Posterior), r=0.65 (Superior-Inferier), r=0.44 (Left-Right).
      Correlations exhibited large inter-patient variability; 60% had r<0.6 in at least
      1 direction thereby resulting in ow correlation between 3D Euclidian shift
      distances (r=0.48). Correlations between 'cw' and kV increased (r>0.8) for
      'implemented' table shifts; only 2 patients demonstrated r<0.6 in any single
      direction. Comparison of consecutively-acquired 'cw' surfaces controlled for
      patient movement demonstrated standard deviations (STDs) of: 1.2mm (A-P), 2.0mm
      (S-I), 1.6mm (L-R). While STDs between 'implemented' and kV shifts were on the
      same order, STDs between 'indicated' and kV shifts were twice as large: 2.9mm (A
      P), 3.5mm (S-I), 4.1mm (L-R). Rotational differences >1degree were calculated
      more often when registering 'cw' (22%) than 'all' (5%). At the treatment
      position, residual STDs remained high (3.0-3.6mm). CONCLUSIONS: On average, 'cw'
      shifts correlated with kV shifts but exhibited significant inter-patient
      variability and larger rotations than 'all'. Differences between AlignRT and kV
      were ~3mm for initial patient positioning. The lack of a one-to-one
      correspondence between surface and kV shifts in any single session must be
      further investigated before clinical implementation.

PMID- 28519799
TI  - SU-E-J-109: Accurate Contour Transfer Between Different Image Modalities Using a
      Hybrid Deformable Image Registration and Fuzzy Connected Image Segmentation
      Method.
AB  - PURPOSE: To develop and evaluate a tool that can improve the accuracy of contour
      transfer between different image modalities under challenging conditions of low
      image contrast and large image deformation, comparing to a few commonly used
      methods, for radiation treatment planning. METHODS: The software tool includes
      the following steps and functionalities: (1) accepting input of images of
      different modalities, (2) converting existing contours on reference images (e.g.,
      MRI) into delineated volumes and adjusting the intensity within the volumes to
      match target images (e.g., CT) intensity distribution for enhanced similarity
      metric, (3) registering reference and target images using appropriate deformable
      registration algorithms (e.g., B-spline, demons) and generate deformed contours,
      (4) mapping the deformed volumes on target images, calculating mean, variance,
      and center of mass as the initialization parameters for consecutive fuzzy
      connectedness (FC) image segmentation on target images, (5) generate affinity map
      from FC segmentation, (6) achieving final contours by modifying the deformed
      contours using the affinity map with a gradient distance weighting algorithm. The
      tool was tested with the CT and MR images of four pancreatic cancer patients
      acquired at the same respiration phase to minimize motion distortion. Dice's
      Coefficient was calculated against direct delineation on target image. Contours
      generated by various methods, including rigid transfer, auto-segmentation,
      deformable only transfer and proposed method, were compared. RESULTS: Fuzzy
      connected image segmentation needs careful parameter initialization and user
      involvement. Automatic contour transfer by multi-modality deformable registration
      leads up to 10% of accuracy improvement over the rigid transfer. Two extra
      proposed steps of adjusting intensity distribution and modifying the deformed
      contour with affinity map improve the transfer accuracy further to 14% averagely.
      CONCLUSIONS: Deformable image registration aided by contrast adjustment and fuzzy
      connectedness segmentation improves the contour transfer accuracy between multi
      modality images, particularly with large deformation and low image contrast.

PMID- 28519800
TI  - SU-E-J-81: Beveled Needle Tip Detection Error in Ultrasound-Guided Prostate
      Brachytherapy.
AB  - PURPOSE: To quantify the needle tip detection errors in ultrasound images due to
      bevel-tip orientation in relation to the location on template grid. METHODS:
      Transrectal ultrasound (TRUS) system (BK Medical) with physical template grid and
      18-gauge bevel-tip (20-deg beveled angle) brachytherapy needle (Bard Medical,
      Covington, GA) were used. The TRUS was set at 6.5MHz in water phantom at 40
      degrees C and measurements were taken with 50% and 100% TRUS gains. Needles were
      oriented with bevel-tip facing up (0-degree) and inserted through template grid
      holes. Reference needle depths were measured when needle tip image intensity was
      bright enough for potentially consistent readings. High-resolution digital
      vernier caliper was used to measure needle depth. Needle bevel-tip orientation
      was then changed to bevel down (by rotating 180-degree) and needle depth was
      adjusted by retracting so that the needle-tip image intensity appeared similar to
      when the needle bevel-tip was at 0-degree orientation. Clinically relevant
      locations were considered for needle placement on the template grids (1st row to
      9th row, and 'a-f' columns). RESULTS: For 50% TRUS gain, bevel tip detection
      errors/differences were 0.69+/-0.30mm (1st row) to 3.23+/-0.22mm (9th row) and
      0.78+/-0.71mm (1st row) to 4.14+/-0.56mm (9th row) in columns 'a' and 'D',
      respectively. The corresponding errors for 100% TRUS gain were 0.57+/-0.25mm to
      5.24+/-0.36mm and 0.84+/-0.30mm to 4.2+/-0.20mm in columns 'a' and 'D',
      respectively. These errors/differences varied linearly for grid-hole locations on
      the rows and columns in between, smaller to large depending on distance from the
      TRUS probe. Observed no effect of gains (50% vs. 100%) along 'D' column, which
      was directly above the TRUS probe. CONCLUSIONS: Experiment results revealed that
      the beveled needle tip orientation could significantly impact the detection
      accuracy of the needle tips, based on which the seeds might be delivered. These
      errors may lead to considerable dosimetric deviations in prostate brachytherapy
      seed implantation.

PMID- 28519801
TI  - SU-E-J-120: Characterization of 4D Lung Ventilation Based on 4DCT Lung Density.
AB  - PURPOSE: To characterize patient's 4D lung ventilation and motion using 4DCT
      images aiming to extract pulmonary features for developing a biomechanical model
      to predict lung tumor motion. METHODS: 4DCT images of sixteen patients were used
      for initial 4D-ventilation evaluation. A program was developed for visualization
      and quantification of 4D lung ventilation. Lung density gradient and pleural
      pressure variation were evaluated based on the gravity. Freeform deformable image
      registration (DIR) was applied to map the lung density from one phase to another,
      with linearly interpolated voxel density. The warped lung density from a
      secondary CT was compared with the primary CT (full-exhalation) for
      quantification. To minimize the uncertainty from motion artifacts for
      quantitative ventilation/motion analysis, we developed two screening algorithms
      (based on Fourier Transformation and Generalized Linear Regression) to quantify
      the regularity (score: 0 to 1) of the RPM waveform, assuming the higher the
      regularity in RPM the less motion artifacts in 4DCT. Ninety-seven RPM curves (54
      free-breathing and 43 audio-coaching patients) were used to qualitatively test
      these screening methods. RESULTS: Lung density gradient in anterior-posterior
      direction for supine patients is observed in 15/16 patients at scale of >100
      200HU. The gravity pressure due to lung tissue weight is estimated to be ~4mmHg,
      which could neutralize the pleural pressure at the posterior chest wall. The
      different pleural pressures at anterior/posterior chest walls may explain the
      difference in local diaphragm muscle engagement and motion range: 8+/-5mm
      (anterior) and 23+/-12mm (posterior). Motion artifacts and DIR uncertainty
      affected quantitative ventilation mapping. In the RPM regularity assessment,
      audiocoaching patients score higher than free-breathing patients: 0.76+/-0.13 vs.
      0.50+/-0.19 (Fourier method) and 0.74+/-0.19 vs. 0.66+/-0.17 (Regression method).
      High-quality 4DCTs can be readily selected for further quantitative
      ventilation/motion analysis. CONCLUSIONS: We have characterized several basic
      features of lung ventilation and motion and developed two effective screening
      methods for high-quality 4DCT for on-going quantitative studies.

PMID- 28519802
TI  - SU-E-J-91: FFT Based Medical Image Registration Using a Graphics Processing Unit
      (GPU).
AB  - PURPOSE: To evaluate the efficiency gains obtained from using a Graphics
      Processing Unit (GPU) to perform a Fourier Transform (FT) based image
      registration. METHODS: Fourier-based image registration involves obtaining the FT
      of the component images, and analyzing them in Fourier space to determine the
      translations and rotations of one image set relative to another. An important
      property of FT registration is that by enlarging the images (adding additional
      pixels), one can obtain translations and rotations with sub-pixel resolution. The
      expense, however, is an increased computational time. GPUs may decrease the
      computational time associated with FT image registration by taking advantage of
      their parallel architecture to perform matrix computations much more efficiently
      than a Central Processor Unit (CPU). In order to evaluate the computational gains
      produced by a GPU, images with known translational shifts were utilized. A
      program was written in the Interactive Data Language (IDL; Exelis, Boulder, CO)
      to performCPU-based calculations. Subsequently, the program was modified using
      GPU bindings (Tech-X, Boulder, CO) to perform GPU-based computation on the same
      system. Multiple image sizes were used, ranging from 256*256 to 2304*2304. The
      time required to complete the full algorithm by the CPU and GPU were benchmarked
      and the speed increase was defined as the ratio of the CPU-to-GPU computational
      time. RESULTS: The ratio of the CPU-to- GPU time was greater than 1.0 for all
      images, which indicates the GPU is performing the algorithm faster than the CPU.
      The smallest improvement, a 1.21 ratio, was found with the smallest image size of
      256*256, and the largest speedup, a 4.25 ratio, was observed with the largest
      image size of 2304*2304. CONCLUSIONS: GPU programming resulted in a significant
      decrease in computational time associated with a FT image registration algorithm.
      The inclusion of the GPU may provide near real-time, sub-pixel registration
      capability.

PMID- 28519803
TI  - SU-E-J-102: The Impact of the Number of Subjects for Atlas-Based Automatic
      Segmentation.
AB  - PURPOSE: To determine the impact of atlas size on the performance of atlas-based
      automatic segmentation (ABAS) in delineation of organs at risk for adaptive
      radiation therapy. METHODS: A total of 25 patients who had undergone intensity
      modulated radiation therapy for various head and neck cancers were
      retrospectively selected for inclusion in a library to be used for ABAS with the
      MIM VISTA software package (MIM Software, Cleveland OH). Treatment planning
      computed tomography (CT) scans and subsequent organ at risk (OAR) contours
      generated as part of the treatment planning process for these patients were added
      to the library. This library of 25 patients was then successively pruned to
      generate 5 atlases with 25, 20, 15, 10, and 5 patient subjects respectively.
      Atlas based segmentation was performed on 10 retrospectively selected treatment
      planning CT scans to automatically generate right and left parotid glands and
      brainstem contours. These planning CT scans belonged to a unique set of 10
      patient subjects different from the ones used for generating the atlases. One
      physician (JW), who was blinded to the ABAS results, manually delineated gold
      standard contours for the right and left parotid glands and brainstem. Dice
      similarity coefficients were calculated and analyzed as a function of atlas
      subject size. RESULTS: For the sites selected in this study, the performance of
      ABAS was relatively insensitive to atlas size. Furthermore, some patient subjects
      were repeatedly selected implying that the adoption of a single standard patient
      for ABAS may be of benefit. CONCLUSIONS: Our preliminary results indicate that
      the performance of the atlas based segmentation module in MIM VISTA Version 5.2
      for the organs studied here may be relatively insensitive to the atlas size.

PMID- 28519804
TI  - SU-E-J-74: Evaluation of the Commercial Prototype Open Face Mask Used with
      Surface Rendering Imaging System for Proton Therapy Patients with Cancers of the
      Brain and Head: Successful Preclinical Study.
AB  - PURPOSE: Evaluation of the commercial prototype open face mask (Fibreplast, Q
      FixTM) used with surface rendering imaging system (AlignRTTM, London, UK) for
      setup and monitoring of proton therapy patients with cancers of the brain and
      head. METHODS: Fibreplastic open face masks were used with Base-of-Skull
      frame/moldcare pillow. Two sizes of the pre-made cutouts in the masks were
      investigated: leaveing open skin surface in the oval-shaped area between (I)
      upper lip and forehead boss, II) between mandible and forehead boss in superior
      inferior direction; and between zygomatic (cheek-) bones/sphenoid bones
      laterally. Calibration of AlignRT system was verified with SRS cube phantom
      (VisionRT)and 2D X-ray patient positioning system (DIPS, IBA). The accuracy of
      translational shifts and rotations was a) verified using a head&neck phantom and
      b) tested using volunteers. Within AlignRT software, only the open area was used
      as ROI for the registration; the option 'Intracranial SRS' used for surface
      capture. RESULTS: For the isocenter determination accuracy within 0.3mm/0.2
      degrees, the head&neck phantom registration was performed with the 0.5mm/0.5
      degree accuracy; the volunteer tests showed the registration accuracy within
      0.5mm +/-0.2mm (1 s)/0.7+/-0.2 (1 s) degree. The simulation of the noise in the
      surface data such as eye blinking and attempts to swallow/chew was performed,
      with negligible effect on the registration. No significant differences between
      the study results between the masks of type (I) and (II) were noticed.
      CONCLUSIONS: The AlignRT surface rendering system has sufficient accuracy when
      used with the open face head&neck mask for localization/registration of the
      proton therapy patients with tumors of the head and brain.

PMID- 28519805
TI  - SU-E-J-113: A New Quantification Measure of the Difference Between Two Organ
      Contours.
AB  - PURPOSE: To develop a measuring method between two contours, which can be used
      for validating a PTV during IGRT, organ motion and/or deformation studies.
      METHODS: Quantifying the geometric difference between two organ/target surfaces
      is essential for Radiation therapy planning and delivery. Point-to-surface
      distance measures have been utilized to evaluate and visualize the local surface
      differences. However, previously well-known distance measures have critical
      shortfalls. Normal distance (ND) measure suffers when the reference surface is
      strongly curved. Minimum distance (MD) measure (a.k.a. Hausdorff distance)
      suffers when the test surface is strongly curved. Our new distance measure named
      Error-Proof Distance (EPD) can deal with both difficult cases.EPD measure
      calculates the maximum value between the Forward Minimum Distance (FMinD) and the
      Backward Maximum Distance (BMaxD) at each point. The FMinD denotes the minimum
      distance to the test surface from a point on the reference surface. The BMaxD
      means the maximum value among the minimum distances from all points of the test
      surface to the point on the reference surface. We tested EPD using three 2-D
      contour examples including a 20mm shifted contour, and two 3-D clinical cases.
      RESULTS: In case of 2-D contour examples, ND and MD measure failed in strongly
      curved areas, but EPD measure outperformed the others. The maximum distance
      measured between a reference and a 20mm shifted test contour should be equal to
      20mm, but ND erroneously measured 24mm. Furthermore, ND reported erroneous
      distances where the reference surface is strongly curved in 3-D clinical cases.
      CONCLUSIONS: We succeeded to prove that a new EPD is arobust and accurate
      distance measure to compare two 2D or 3D surfaces. EPD measure can be used to
      evaluate and visualize the surface difference of organ contours. It is also
      helpful for proving PTV margin during IGRT, and organ motion and/or deformation
      studies. This project is partially supported by the Agency for Healthcare
      Research and Quality (AHRQ) grant 1R18HS017424-01A2.

PMID- 28519806
TI  - SU-E-J-62: Comparison of Brainlab ExacTrac, AlignRT, and CBCT Positional Accuracy
      for SRS Set-Up on a TrueBeam STx.
AB  - PURPOSE: To compare the ability of Brainlab ExacTrac (Brainlab AG, Feldkirchen,
      Germany) x-ray (XRAY), Brainlab infrared array (IR), cone beam CT (CBCT), and
      AlignRT (VisionRT Ltd., London, UK) to accurately measure patient displacement
      during stereotactic radiosurgery (SRS) on a Varian TrueBeam STx (Varian Inc, Palo
      Alto, CA). METHODS AND MATERIALS: A CT scan was obtained for a custom skull
      phantom placed in a Brainlab frameless SRS immobilization system with the
      Brainlab CT localizer box attached. A generic plan was created in Brainlab iPlan
      and sent to Brainlab ExacTrac, to AlignRT, and to the TrueBeam. The skull phantom
      was set-up on the TrueBeam and positioned to isocenter using XRAY. Next, CBCT and
      IR were acquired and evaluated to determine baseline positions for these methods.
      A new AlignRT reference surface was acquired as baseline. The phantom was then
      displaced 2 mm in the vertical, lateral, and longitudinal dimensions using the
      TrueBeam couch (the couch tolerance is 0.1 mm in each dimension). New XRAY, IR,
      CBCT, and AlignRT data was acquired in this position. RESULTS: Initially, all
      methods found that the phantom was positioned with < 0.3 mm accuracy. After the
      shiftes, XRAY suggested shifts were 2.0, 2,1, 1.8 mm in the vertical,
      longitudinal, and lateral dimensions, respectively. The IR shifts were 1.7, 2.6,
      2.1 mm. The CBCT shifts were 1.8, 1.8, 2.1 mm. The AlignRT shifts were 2.2, 1.6,
      1.4 mm. CONCLUSION: The internal XRAY and CBCT methods produced slightly better
      agreement with the table shifts. The external IR and AlignRT methods were less
      accurate, but still gave agreement of <= 0.6 mm. Note, the AlignRT cameras did
      not produce a clean surface off of the phantom. Improved accuracy is expected
      from a skin surface. This is preliminary work, more extensive study is needed to
      evaluate these methods.

PMID- 28519808
TI  - SU-E-J-104: Evaluation of Atlas-Based Auto-Segmentation on Daily In-Room CT for
      Prostate Cancer.
AB  - PURPOSE: Anatomy delineation is a major time consuming task to correct for inter
      fractional changes in anatomy. Atlas-based auto-segmentation (ABAS) was developed
      to expedite this process. This study aims to evaluate the performance of ABAS
      applying to high quality verification CT-imaging acquired using a CT-on-rail
      system for prostate cancer. METHODS: The prostate, rectum and bladder were
      manually contoured for seven prostate cancer patients. For each patient, three
      patient specific atlases were generated consisting of one, four and seven prior
      image and contour sets. ABAS was applied using these atlases for the last seven
      daily CT images of each patient. The auto- and manual-contours were compared both
      geometrically and dosimetrically. The reproducibility of the observation was
      validated by an experienced radiation oncologist performing the same procedure.
      The performance of ABAS with patient and non-patient specific atlases were also
      evaluated on 21 image sets. P<0.05 was considered statistical significant for two
      tailed paired student t-test. RESULTS: Contours obtained from ABAS agreed well
      with the manual ones. With 1-image set atlas, the OI and DSC for the bladder were
      greater than 96% and 91%, respectively. Both indices were above 81% for rectum
      and prostate. The consistencies significantly improved by including 4 image sets
      in the atlas, while a further increase of atlas size to 7 did not show obvious
      benefits. Dose coverage for the auto- and manual-contours was similar for all
      organs. Similar results were obtained by the second observer. Compared with non
      patient specific atlas, patient specific atlas yielded more accurate contours.
      The time for ABAS and manual contouring was ~2 min and ~20 min per image set,
      respectively. CONCLUSIONS: With diagnostic quality verification images, ABAS can
      provide fast and accurate delineations for prostate cancer on a daily basis. The
      inclusion of more than one CT set in atlas improves the contouring results.

PMID- 28519807
TI  - SU-E-J-65: Feasibility Study of Backscatter Imaging for Image-Guided
      Radiotherapy.
AB  - PURPOSE: Tracking tumor motion during external beam radiation therapy is a major
      factor limiting the treatment of lung tumors. Several tracking techniques have
      been previously reported; however, these are limited to 2D motion, fail to
      capture image data during treatment delivery (e.g., patient setup imaging), fail
      to capture motion along the beam axis (MV CineMode), or increase patient dose (kV
      fluoroscopy). Creating images from radiation that is naturally scattered from the
      patient during treatment could overcome the limitations of other techniques. This
      study investigated the feasibility of using photon scatter to create images
      during external beam radiation delivery. METHODS: A prototype imager was created
      using a Trilogy Linac, pinhole collimator, and computed radiography (CR) plate.
      Two small cylinders (solid water and cerrobend) were placed in the path of a 6MV
      beam. The collimator/CR plate was placed at 45 degrees  and 90 degrees  from the
      gantry head and 2000MU was delivered. Optically-stimulated luminescent (OSLD)
      detectors were placed on the surface of the CR plate to measure photon dose.
      Contrast-to-noise ratios (CNR) were calculated for each peg to assess image
      quality. RESULTS: At 45 degrees , OSLD dose was 1.3+/-0.2cGy and the CNRs were
      1.5 and 5.3 for water and cerrobend, respectively. OSLD dose increased to 2.6+/
      0.3cGy and CNR increased to 14.8 and 18.3 at 90 degrees . Scatter from the gantry
      head and the pinhole collimator are the major sources of noise which limit image
      quality. The measured CNR satisfied the Rose criteria for detectability (CNR > 3
      5) for the 90 degrees  gantry orientation. Further, scatter imaging should
      satisfy the Rose criteria if output is reduced from 2000MU to 200MU. CONCLUSIONS:
      Preliminary results confirm the feasibility of using scatter imaging for in situ
      treatment monitoring. Future work will investigate creation of tomosynthesis
      images and improving image quality using increased shielding and a multi-pinhole
      collimator.

PMID- 28519809
TI  - SU-E-J-76: Clinical Use of a Real-Time Surface Image-Guided Positioning and
      Tracking System in Proton Therapy.
AB  - : Topic of interest: Clinical applications of AlignRT 3-cameras real-time surface
      image-guided positioning system (IGPS) for positioning patients to reduce the
      number of X-ray images and tracking intra-fractional movements in proton therapy.
      PURPOSES: To position patients and track the intra-fractional movements, the
      AlignRT system was implemented in proton incline-beam-line (IBL) at Procure
      Oklahoma-City center. METHODS: The AlignRT3c system was configured near
      perpendicular to the gantry rotation for accommodating the X-ray IGPS. To
      evaluate positioning accuracy, more than 10 surfaces of each patient for ten
      patients with intracranial tumors were acquired after patients positioned by X
      ray IGPS. Displacements between acquired surfaces and the reference surface taken
      at 1st day of treatment were examined. Intra-fractional movements with
      respiratory was studied with gated surface that allows setting the reference
      surface for patient at exhale during breathing. Intra-fractional movements due to
      respiratory were monitored on 10 sections of each patient for three patients with
      thoracic tumors. RESULTS: Accuracy of positioning patient is 2.0 mm at both
      anterior-posterior and lateral directions, and is 3.5 mm in superior-inferior
      (SI) direction by aligning the surfaces of masks. Observed larger displacements
      along SI direction can be due to patient's movements within the mask. Periodical
      displacements within 5 mm compared to its reference were seen for the three
      patients with thorax tumors. However, 10 mm sharp displacements with a few
      seconds were observed when patient moved the body. CONCLUSIONS: We have
      implemented the first AlignRT3c IGPS for proton therapy for positioning patients
      within 2.0 mm, and successfully tracked intra-fractional respiratory motion
      during treatment after positioning patient.

PMID- 28519810
TI  - SU-E-J-115: Graticule for Verification of Treatment Position in Neutron Therapy.
AB  - PURPOSE: Until recently the treatment verification for patients undergoing fast
      neutron therapy at our facility was accomplished through a combination of neutron
      beam portal films aligned with a graticule mounted on an orthronormal x-ray tube.
      To eliminate uncertainty with respect to the relative positions of the x-ray
      graticule and the therapy beam, we have developed a graticule which is placed in
      the neutron beam itself. METHODS: For a graticule to be visible on the portal
      film, the attenuation of the neutron beam by the graticule landmarks must be
      significantly greater than that of the material in which the landmarks are
      mounted. Various materials, thicknesses, and mounting points were tried to gain
      the largest contrast between the graticule landmarks and the mounting material.
      RESULTS: The final design involved 2 inch steel pins of 0.125 inch diameter
      captured between two parallel plates of 0.25 inch thick clear acrylic plastic.
      The distance between the two acrylic plates was 1.625 inches, held together at
      the perimeter with acrylic sidewall spacers. This allowed the majority of length
      of the steel pins to be surrounded by air. The pins were set 1 cm apart and
      mounted at angles parallel to the divergence of the beam dependent on their
      position within the array. The entire steel pin and acrylic plate assembly was
      mounted on an acrylic accessory tray to allow for graticule alignment.
      CONCLUSION: Despite the inherent difficulties in attenuating fast neutrons, our
      simple graticule design produces the required difference of attenuation between
      the arrays of landmarks and the mounting material. The graticule successfully
      provides an in-beam frame of reference for patient portal verification.

PMID- 28519811
TI  - SU-E-J-87: Building Deformation Error Histogram and Quality Assurance of
      Deformable Image Registration.
AB  - PURPOSE: To quantify the systematic error of a Deformable Image Registration
      (DIR) system and establish Quality Assurance (QA) procedure. METHODS: To address
      the shortfall of landmark approach which it is only available at the significant
      visible feature points, we adapted a Deformation Vector Map (DVM) comparison
      approach. We used two CT image sets (R and T image sets) taken for the same
      patient at different time and generated a DVM, which includes the DIR systematic
      error. The DVM was calculated using fine-tuned B-Spline DIR and L-BFGS optimizer.
      By utilizing this DVM we generated R' image set to eliminate the systematic error
      in DVM,. Thus, we have truth data set, R' and T image sets, and the truth DVM. To
      test a DIR system, we use R' and T image sets to a DIR system. We compare the
      test DVM to the truth DVM. If there is no systematic error, they should be
      identical. We built Deformation Error Histogram (DEH) for quantitative analysis.
      The test registration was performed with an in-house B-Spline DIR system using a
      stochastic gradient descent optimizer. Our example data set was generated with a
      head and neck patient case. We also tested CT to CBCT deformable registration.
      RESULTS: We found skin regions which interface with the air has relatively larger
      errors. Also mobile joints such as shoulders had larger errors. Average error for
      ROIs were as follows; CTV: 0.4mm, Brain stem: 1.4mm, Shoulders: 1.6mm, and Normal
      tissues: 0.7mm. CONCLUSIONS: We succeeded to build DEH approach to quantify the
      DVM uncertainty. Our data sets are available for testing other systems in our web
      page. Utilizing DEH, users can decide how much systematic error they would
      accept. DEH and our data can be a tool for an AAPM task group to compose a DIR
      system QA guideline. This project is partially supported by the Agency for
      Healthcare Research and Quality (AHRQ) grant 1R18HS017424-01A2.

PMID- 28519812
TI  - SU-E-J-97: Evaluation of Multi-Modality (CT/MR/PET) Image Registration Accuracy
      in Radiotherapy Planning.
AB  - PURPOSE: Evaluate accuracy of multi-modality image registration in radiotherapy
      planning process. METHODS: A water-filled anthropomorphic head phantom containing
      eight 'donut-shaped' fiducial markers (3 internal + 5 external) was selected for
      this study. Seven image sets (3CTs, 3MRs and PET) of phantom were acquired and
      fused in a commercial treatment planning system. First, a narrow slice (0.75mm)
      baseline CT scan was acquired (CT1). Subsequently, the phantom was re-scanned
      with a coarse slice width = 1.5mm (CT2) and after subjecting phantom to
      rotation/displacement (CT3). Next, the phantom was scanned in a 1.5 Tesla MR
      scanner and three MR image sets (axial T1, axial T2, coronal T1) were acquired at
      2mm slice width. Finally, the phantom and center of fiducials were doped with 18F
      and a PET scan was performed with 2mm cubic voxels. All image scans (CT/MR/PET)
      were fused to the baseline (CT1) data using automated mutual-information based
      fusion algorithm. Difference between centroids of fiducial markers in various
      image modalities was used to assess image registration accuracy. RESULTS: CT/CT
      image registration was superior to CT/MR and CT/PET: average CT/CT fusion error
      was found to be 0.64 +/- 0.14 mm. Corresponding values for CT/MR and CT/PET
      fusion were 1.33 +/- 0.71mm and 1.11 +/- 0.37mm. Internal markers near the center
      of phantom fused better than external markers placed on the phantom surface. This
      was particularly true for the CT/MR and CT/PET. The inferior quality of external
      marker fusion indicates possible distortion effects toward the edges of MR image.
      Peripheral targets in the PET scan may be subject to parallax error caused by
      depth of interaction of photons in detectors. CONCLUSIONS: Current widespread use
      of multimodality imaging in radiotherapy planning calls for periodic quality
      assurance of image registration process. Such studies may help improve safety and
      accuracy in treatment planning.

PMID- 28519813
TI  - SU-E-J-69: Development of an Ambiguity-Free Optical Tracking System for SBRT.
AB  - PURPOSE: Commercial optical tracking system such as BrainLab ExacTrac(c) suffers
      from ambiguous markers which can cause significant delay in patient treatment. We
      developed an ambiguity-free optical tracking system for high precision SBRT.
      METHODS: The optical tracking system consists of a pair of camera sensors, 4~8
      infra-red (IR) reflective markers affixed on patient skin and in-house developed
      software. We developed an effective algorithm to automatically eliminate
      ambiguous markers. A recursive backtracking algorithm was developed to build one
      to-one correspondence between reference markers and optical markers. The
      algorithm was able to deal with missing, misplaced, or occluded markers by
      introducing 'dummy' markers. Isocenter displacements were calculated in six
      degree of freedom through rigid-body registration between reference markers and
      optical markers. The system accuracy was evaluated with a pelvis phantom against
      cone beam CT (CBCT) and ExacTrac. The impact of number of markers on tracking
      accuracy was also evaluated. The performance of automatic ambiguity elimination
      was assessed with synthetic and clinic marker patterns. RESULTS: Difference of
      isocenter displacement reported by our system and commercial systems (CBCT,
      ExacTrac) were within 0.5 mm/0.1o. Impact of number of markers on tracking
      accuracy in our phantom test was negligible with isocenter displacement varying
      within 0.2 mm/0.2o when number of markers varied from 4 to 8. The system
      successfully identified and eliminated ambiguous markers in both synthetic and
      clinic marker patterns. CONCLUSIONS: An accurate optical tracking system free of
      ambiguous markers was developed for patient positioning and monitoring in high
      precision SBRT. The developed algorithms to eliminate ambiguous markers and to
      handle missing, misplaced or occluded markers were effective and efficient.

PMID- 28519815
TI  - SU-E-J-80: A Simulation Study with Geant4 on the Yields of Positron-Emitting
      Nuclei (10C, 11C, and 15O) Induced by Protons and Carbon Ions.
AB  - PURPOSE: To study the yields and the depth-distributions of positron-emitting
      nuclei (PEN) 10C, 11C, and 15O induced by protons and carbon ions in PMMA.
      METHODS: An application built with various physics packages was constructed with
      Geant4 Monte Carlo Toolkit. A phantom of 15 cm * 15 cm * 50 cm consisting of PMMA
      (C5H8O2, density 1.18 g/cm3 ) was irradiated with 70, 110 MeV protons and 204 A,
      212.12 A MeV carbonions. Beam quality of 1 cm FWHM with 0.2% Gaussian energy
      spread FWHM was used. For each beam energy, simulation of the energy deposited
      was recorded for every 1 mm increment of depth in the phantom. The resulting PEN
      and their yields were recorded at the production point and also at the point of
      decay in increments of 1 mm. RESULTS: The overall percentage yields, depth
      distributions, and total percentages of PEN per incident particle for both
      protons and carbon ions were obtained. Our results found that the predominant
      PMMA fragment was 11C irrespective of incident particle type or energy.
      CONCLUSIONS: Our yields of PEN are comparable with other simulations (FLUKA and
      MCHIT) as well as existing experimental data. The present work however
      overestimates the percentage of PEN in the simulations of incident carbon ions
      and the percentage of 10C for incident protons compared to the experimental data.
      This particular application built within the Geant4 Monte Carlo Toolkit can
      estimate the amount of PEN as well as the depth-distributions of these nuclei in
      hadron induced radiation therapy.

PMID- 28519814
TI  - SU-E-J-108: Quantitative Analysis of Longitudinal Cognitive Impairment Due to
      Radiation Therapy Based on Automatic Segmentation of Hippocampus and Subcortical
      Structure.
AB  - PURPOSE: In this study, we developed a quantitative analysis tool based on
      patient's longitudinal MR images to 1) measure the radiation dose received by
      each subcortical structure, 2) follow the change of volume and shape of each
      structure longitudinally. This tool provides a systematic approach to study the
      radiation therapy (and subsequent chemotherapy) associated with cognitive
      impairments. METHODS: MRI scans of one patient taken before and after radiation
      therapy are demonstrated in this study. 3D Conformal radiation therapy was
      performed on RapidArcTM. An open source MRI analysis tool, FMRIB's Integrated
      Registration and Segmentation Tool (FIRST), was used for segmentation. The images
      are registered to a standard template with expert-defined labeling for all sub
      cortical structures, and the labeling of each structure is mapped back to the
      individual MRI space for segmentation. After the segmentation, the radiation dose
      map was coregistered to the MRI space to calculate the dose received by each
      structure. RESULTS: For the structure that is contained within the radiation
      zone, we can calculate the total dose based on the volumetric distribution of
      radiation dose. For the structure that is outside the radiation field, we can
      calculate the distance from the radiation zone. We have demonstrated in this work
      that the analysis can be done for all segmented sub-cortical structures. The
      change of volume before and after radiation treatment can be analyzed, and the
      results can be correlated with the change of cognitive performance over time.
      CONCLUSIONS: We presented an automated tool for efficient, quantitative and user
      independent measurements of radiation dose in subcortical structures. The
      obtained results can be correlated with the cognitive test score and the clinical
      outcome to evaluate radiation and the subsequent chemotherapy induced changes in
      brain structures and functions.

PMID- 28519816
TI  - SU-E-J-90: 2D/3D Registration Using KV-MV Image Pairs for Higher Accuracy Image
      Guided Radiotherapy.
AB  - PURPOSE: In this work, we investigate the impact of using paired portal mega
      voltage (MV) and kilo-voltage (kV) images, on 2D/3D registration accuracy with
      the purpose of improving tumor motion tracking during radiotherapy. Tumor motion
      tracking is important as motion remains one of the biggest sources of uncertainty
      in dose application. 2D/3D registration is successfully used in online tumor
      motion tracking, nevertheless, one limitation of this technique is the inability
      to resolve movement along the imaging beam axis using only one projection image.
      METHODS: Our evaluation consisted in comparing the accuracy of registration using
      different 2D image combinations: only one 2D image (1-kV), one kV and one MV
      image (1kV-1MV) and two kV images (2-kV). For each of the image combinations we
      evaluated the registration results using 250 starting points as initial
      displacements from the gold standard. We measured the final mean target
      registration error (mTRE) and the success rate for each registration. Each of the
      combinations was evaluated using four different merit functions. RESULTS: When
      using the MI merit function (a popular choice for this application) the RMS mTRE
      drops from 6.4 mm when using only one image to 2.1 mm when using image pairs. The
      success rate increases from 62% to 99.6%. A similar trend was observed for all
      four merit functions. Typically, the results are slightly better with 2-kV images
      than with 1kV-1MV. CONCLUSIONS: We evaluated the impact of using different image
      combinations on accuracy of 2D/3D registration for tumor motion monitoring. Our
      results show that using a kV-MV image pair, leads to improved results as motion
      can be accurately resolved in six degrees of freedom. Given the possibility to
      acquire these two images simultaneously, this is not only very workflow efficient
      but is also shown to be a good approach to improve registration accuracy.

PMID- 28519817
TI  - SU-E-J-101: Weighted Voting Method for Multi-Atlas Segmentation in CT Scans.
AB  - PURPOSE: We investigate automating the task of segmenting structures in head and
      neck CT scans, to minimize time spent manually contouring. We focus on the
      brainstem and left and right parotids. METHODS: To generate contours for an
      unlabeled image, we assume an atlas of labeled images. We register each of these
      images to the unlabeled target image, transform their structures, and then use a
      weighted voting method for label fusion. Our registration method starts with
      multi-resolution translational alignment, then applies a relatively higher
      resolution affine alignment. We then employ a diffeomorphic demons registration
      to deform each atlas to the space of the targetimage. Our weighted voting method
      acts one structure at a time to determine for each voxel whether or not it exists
      in a structure. The weight for a voxel's vote from each atlas depends on the
      intensity difference of the target and the transformed atlas at that voxel, in
      addition to the distance of that voxel from the boundary of the structure.
      RESULTS: We applied our method to sixteen labeled images, generating automatic
      segmentations foreach using the other fifteen images as the atlas. We compared
      the resulting Dice and Hausdorff metrics with a majority voting method using the
      same registrations and saw remarkable improvement. Mean Dice scores were around
      .7, with maximum Hausdorff of about 15mm, and mean Hausdorffs around 2 or 3mm.
      CONCLUSIONS: Our method produces contours with boundaries usually only a few
      millimeters away from the manual contour, which could save physicians
      considerable time, because they only have to make small modifications to each
      slice instead of contouring from scratch.

PMID- 28519818
TI  - SU-E-J-73: Using Surface-Based Imaging for Patient Identification.
AB  - PURPOSE: A feasibility study to determine if daily surface-based imaging can be
      used for patient identification with reliable accuracy. METHODS: Three
      dimensional surface images were acquired using AlignRT (VisionRT Ltd., London,
      UK) prior to daily radiotherapy treatment for 12 breast cancer patients. These
      were compared retrospectively to body contours generated from computed tomography
      simulation (CT sim) scans. Two types of comparisons were made. The first compared
      the surface of each patient for all fractions of treatment. The second compared a
      random incorrect patient body contour for each patient in the study. The 'surface
      statistic' tool reveals the percentage of surface points within a threshold
      distance of 3mm. RESULTS: Comparison of the patients' daily AlignRT images to the
      CT sim body contour showed similarity of the surfaces of 81.0% +/- 6.6% with a
      total range of 61.5-95.3%. This same comparison of the wrong patient's CT sim
      body contour to a random fraction of another patient's AlignRT image revealed
      similarity of the surfaces of 27.9% +/- 10.2% with a range of 6.7-58.3%. A
      threshold of approximately 60% separates misidentification from correct
      identification in our limited study set. There was no overlap between the two
      groups in our test. However, we recognize that the two groups come close to the
      threshold value and could overlap in a larger study set. CONCLUSIONS: Using daily
      surface-based imaging to identify patients is feasible with AlignRT using a
      surface statistic threshold of approximately 60%. This has the possibility of
      improving radiotherapy safety using existing image-guided technology. Further
      study is needed to better understand the sensitivity and specificity of this tool
      for a larger patient population.

PMID- 28519819
TI  - SU-E-J-112: A Splatting Method to Generate DRRs for Deformed CT Volume.
AB  - PURPOSE: To develop an efficient algorithm for generating high-quality digitally
      reconstructed radiographs (DRRs) for regularly and irregularly sampled volumes
      based on a splatting method with dynamic elliptical Gaussian kernels, and to
      evaluate this method using ray tracing. METHODS: The traditional ray tracing
      method, which takes every intersected voxel into account, produces high quality
      DRRs but is very time consuming. Additionally, it is not suitable for handling
      irregularly-sampled volumes since it always requires image re-sampling, which
      leads to inaccuracy. We present a splatting approach to compute the 'footprint
      function', facilitating efficient perspective projection of elliptical Gaussian
      kernels at very low cost. This reported framework allows dealing with both
      regularly and irregularly sampled volumes effectively and efficiently. An XCAT
      digital phantom was used to generate 3D chest volumes at different respiratory
      phases, and CT projections are generated using ray tracing and the splatting
      method, respectively. Normalized cross correlation (NCC) is applied to evaluate
      the DRR similarity of two methods. RESULTS: Respiratory Phases one and four are
      used as volume datasets from the 4D XCAT digital phantom as they represent the
      lung at end inhale and end exhale, respectively. The dataset of Phase one is the
      basic regularly-sampled volume while the dataset of Phase four is deformed from
      that of Phase one, and resampled to a regularly sampled dataset for the ray
      tracing method. NCC between splatting and ray tracing DRRs are 0.9980 and 0.9977
      for Phase one and Phase four, respectively. The calculation speed of the
      splatting method is 3 times faster than that of ray tracing. CONCLUSIONS: Our
      splatting approach can generate high-quality DRRs efficiently, and is a good
      alternative for current DRR generation techniques for deformed volume datasets.
      This research is supported by CPRIT Individual Investigator Award RP110329.

PMID- 28519820
TI  - SU-E-J-84: Investigating the Use of Deformable Algorithms to Register and
      Accumulate Dose to the Spinal Cord for Head-And-Neck Radiotherapy Patients.
AB  - PURPOSE: Mega-voltage cone-beam CT (MVCBCT) imaging can be used to monitor
      changes in neck flexion and calculate the true spinal cord dose during
      radiotherapy. To sum the dose over multiple fractions and compare with the
      planned dose requires deformable image registration. This study investigates the
      accuracy of deformable registration of the spine in kilovoltage CT (kVCT) to
      MVCBCT images for head-and-neck patients. METHODS: Head-and-neck kVCT and MVCBCT
      images were selected from five patients who exhibited large changes in neck
      flexion. The spinal canal was contoured in each image. MVCBCT images were rigidly
      registered to the kVCT image by aligning the C1-C2 vertebrae. Variations of a
      commercial deformable registration algorithm using the B-spline method were
      applied to a volume of interest surrounding the spine to deform the spinal cord
      structure from the kVCT to the MVCBCT. The Dice similarity index (DSI) was
      calculated between rigidly registered structures (DSI1), and compared against the
      DSI calculated between the MVCBCT structure and the structure deformed from kVCT
      to MVCBCT (DSI2). The difference between DSI2 and DSI1 was calculated to
      investigate the ability of the deformation algorithm to match the change in neck
      flexion. RESULTS: In this data set, a single-pass B-spline deformation algorithm
      was the most effective in deforming the kVCT spinal canal to the MVCBCT spinal
      canal, with a mean improvement in DSI (DSI2 - DSI1) of 0.134. The mean change in
      DSI for a single-pass algorithm with a contrast correction was 0.111; for a
      multiple-pass algorithm was 0.105; and for a multiple-pass algorithm with
      contrast correction was 0.075. CONCLUSIONS: Several versions of a commercially
      implemented B-spline deformation algorithm were found to improve the registration
      of the spinal canal in kVCT and MVCBCT head-and-neck images. The resulting
      accuracy in the calculation of the cumulative dose to the spinal cord is under
      investigation. We acknowledge Velocity for providing the registration software.

PMID- 28519821
TI  - SU-E-J-75: Practical Annual Quality Assurance Program for a Real Time Optical
      Tracking System.
AB  - PURPOSE: To verify the accuracy of a real time optical surface tracking system
      using a practical annual quality assurance program with an anthropomorphic breast
      phantom. METHODS: An anthropomorphic breast phantom was used to determine the
      accuracy of registration, shift, source to surface distance (SSD), and live
      monitoring features of the AlignRT system. Both the two and three camera AlignRT
      systems were tested. Registration and shift accuracy were evaluated by comparing
      software output with known phantom displacements and rotations at 0, 90, and 270
      couch angles. These tests were performed in static capture and live monitoring
      modes. SSD accuracy was determined by comparing AlignRT results with expected
      values from the treatment planning system and optical distance indicator at 0,
      90, and 270 degree couch rotations. RESULTS: For the two camera system,
      registration accuracy at 0, 90, and 270 degree couch angles was within 1.0mm in
      the lateral, longitudinal, and vertical directions and 0.04 degree. For shifts of
      +/-10mm and +/-5 degree, static mode shift accuracy was within 1.6mm and 0.23
      degree. Registration accuracy of the shifted phantom in live monitoring mode was
      within 1.7mm and 0.2 degree. For the three camera system, registration accuracy
      at 0, 90, and 270 degree couch angles was within 1.1 mm in the lateral,
      longitudinal, and vertical directions and 0.2 degree. For shifts of +/-10mm and
      +/-5 degree, static mode shift accuracy was within 0.9mm and 0.2 degree.
      Registration accuracy of the shifted phantom in live monitoring mode was within
      1.1mm and 0.2 degree. SSD determination was accurate to within 2mm for both
      systems and modes. CONCLUSIONS: The AlignRT system accuracy can be easily
      verified for annual quality assurance using a realistic clinical setup to within
      2mm/0.5 degree. System accuracy was comparable for both two and three camera
      systems in static and live monitoring modes.

PMID- 28519822
TI  - SU-E-J-114: Web-Browser Medical Physics Applications Using HTML5 and Javascript.
AB  - PURPOSE: Since 2010, there has been a great attention about HTML5. Application
      developers and browser makers fully embrace and support the web of the future.
      Consumers have started to embrace HTML5, especially as more users understand the
      benefits and potential that HTML5 can mean for the future.Modern browsers such as
      Firefox, Google Chrome, and Safari are offering better and more robust support
      for HTML5, CSS3, and JavaScript. The idea is to introduce the HTML5 to medical
      physics community for open source software developments. The benefit of using
      HTML5 is developing portable software systems. METHODS: The HTML5, CSS, and
      JavaScript programming languages were used to develop several applications for
      Quality Assurance in radiation therapy. The canvas element of HTML5 was used for
      handling and displaying the images, and JavaScript was used to manipulate the
      data. Sample application were developed to: 1. analyze the flatness and symmetry
      of the radiotherapy fields in a web browser, 2.analyze the Dynalog files from
      Varian machines, 3. visualize the animated Dynamic MLC files, 4. Simulation via
      Monte Carlo, and 5. interactive image manipulation. RESULTS: The programs showed
      great performance and speed in uploading the data and displaying the results. The
      flatness and symmetry program and Dynalog file analyzer ran in a fraction of
      second. The reason behind this performance is using JavaScript language which is
      a lower level programming language in comparison to the most of the scientific
      programming packages such as Matlab. The second reason is that JavaScript runs
      locally on client side computers not on the web-servers. CONCLUSIONS: HTML5 and
      JavaScript can be used to develop useful applications that can be run online or
      offline on different modern web-browsers. The programming platform can be also
      one of the modern web-browsers which are mostly open source (such as Firefox).

PMID- 28519823
TI  - SU-E-J-86: Free form Deformable Model Based on Multi-Resolution B-Spline Grid for
      Registration of 4D CT Images of Hepatocellular Carcinoma Patients.
AB  - PURPOSE: The breathing motion has a significant influence to radiation therapy of
      hepatocellular carcinoma patients, and the motions are irregular. We used
      deformable registration of four-dimensional computed tomography (4D CT) data to
      eliminate breathing motion artifact to truly track the tumors' positions and
      shapes, and guide medical physicists to delineate the more accurate tumor targets
      for treatment planning. METHODS: We collected 4D CT data of 8 hepatocellular
      carcinoma patients, 4D-CT images were segmented into 10 serious CT images
      according the respiratory phase, and named CT0,CT10'|CT90, and CT0 was at end
      inspiration, CT50 was at end expiration. We proposed the free form deformable
      (FFD) model based on multi-resolution B-spline grid registration method to the 4D
      CT data during a whole breathing cycle, and we used L-BFGS to optimize system and
      multi-resolution to pick up the registration speed and accuracy. In particular we
      defined the gross target volume of HCC with the help of iodipin on CT images
      which can verify the registration performance. We chose end-exhale CT as the
      reference image. RESULTS: We compared the floating images, the subtractions of
      floating images and reference image, the iodipin landmarks' positions and the
      multi-informations between floatings image and reference image before and after
      registered to verify the registration performance. From the registered images, we
      can track the 'trajectory' of the tumors during a whole breathing cycle, and the
      average multi-information improved 3.5% after registration between the two
      extreme phases. CONCLUSIONS: Wecan use this registration method to register the
      4D CT data and use iodipin on CT images to define gross target volume to guide
      medical physicists delineating the more accurate tumor targets.

PMID- 28519824
TI  - SU-E-J-96: Investigation into the Accuracy of Deformable Registration Algorithms
      for Use in Dose Summation: A Case Study in Combined Modalities.
AB  - PURPOSE: To better understand the accuracy and limitation of deformable
      registration algorithms for dose summation by studying the results produced
      through two different deformable registration techniques for a clinical case of
      combining a Cyberknife radiosurgery plan and an electron boost to the scar
      tissues. METHODS: A patient was treated with a Cyberknife plan with supine CT and
      an electron boost plan with prone CT concurrently. The CT, RT structures and dose
      grids were exported from the Cyberknife MultiPlan system and the Pinnacle system
      and imported into two commercial DICOM viewing systems equipped with deformable
      registration algorithms. One of the systems uses intensity-based free-form
      deformable registration while the other uses B-spline free-form deformable
      registration. The electron boost plan was first registered to the CK plan using
      rigid registration, then secondly using deformable registration in each system.
      The region of interest used for registration was chosen to encompass the whole CT
      volumes due to the supine vs. prone positions. RESULTS: The summation doses for
      the Cyberknife CTV and critical structures do not differ between rigid
      registration and deformable registration for both systems. The electron boost
      volume does show higher mean dose received for the deformable registration
      compared with rigid registration for both systems (12.90 Gy vs. 11.71 Gy and
      12.39 Gy vs. 11.53 Gy). There are slight variations between the doses produced by
      the two systems for all the structures, with an averaged difference of
      approximately 0.02% to 2.63%. CONCLUSIONS: These results show that for cases like
      this one, where the two treatment volumes do not overlap, there will not be
      significant differences between rigid and deformable registration, and that the
      only significant difference in summation dose between the different deformable
      registration algorithms is where the volume is deformed the most, in this case,
      the electron boost volume.

PMID- 28519825
TI  - SU-E-J-68: An Optical Image Guidance System: To Detect Arbitrarily Attached
      Markers Behind a Full Facemask.
AB  - PURPOSE: We developed an optical image guidance system to manage patient's inter
      fractional set-up errors by tracking external markers at the specific positions
      (e.g., nose tip) behind a full facemask. However, a problem associated with the
      reproducibility of the marker positions during the entire course of treatments
      still remains. In order to remove this disadvantage, we applied the arbitrary
      point-to-plane registration method to our existing system. METHODS: Infra-red
      (IR) reflecting markers were attached on arbitrary positions of the head
      phantom's face and then the phantom was immobilized by a full face thermoplastic
      mask. 3D coordinates of the IR markers behind the full facemask were
      reconstructed by the calibrated stereo camera system using the direct linear
      transform (DLT) algorithm. In order to match arbitrarily attached markers with a
      planning CT image, rough positions of three markers were manually defined (rough
      registration) and then the coordinates of all markers were determined through the
      point-to-plane registration using the contractive projection point (CPP)
      algorithm (fine registration). In addition, the marker registration error in 6
      DOF was calculated. In order to validate accuracy of the system, the phantom was
      intentionally moved according to 10 sets of known translation parameters.
      RESULTS: A mean target registration error (TRE) determined by the experiments for
      arbitrarily attached markers was 1.24 +/- 0.32 mm. The fine registration
      following the rough registration allowed fast and robust registrations.
      CONCLUSIONS: The proposed solution for arbitrarily attached markers behind a full
      facemask enables us to avoid any daily errors in attaching the external markers
      at the specific positions. This work was supported in part by the SNU
      interdisciplinary project (2009-2010) and the SNU Brain Fusion project (2010
      2011).

PMID- 28519826
TI  - SU-E-J-107: Feasibility of Complete Brain Simulation Using Single MRI
      Acquisition.
AB  - PURPOSE: To evaluate the information available from a single MRI acquisition for
      a complete MRI-based simulation in brain. METHOD AND MATERIALS: A 3.0T MRI
      scanner (Achieva TX, Philips Healthcare) was used to acquire a complete brain
      simulation data set in a single acquisition on four consenting volunteers. The
      acquisition consisted of collecting the FID signal (TE1 = 100MUs) followed by two
      additional gradient echoes (TE2/TE3= 1.4ms/2.5ms) using a 3D volumetric
      excitation and radial read-out toachieve 1.3mm isotropic voxels. The data from
      this single acquisition was used to reconstruct five volumetric data sets: Bone
      enhanced, fat-only, water-only, in-phase and out-of-phase. The resulting image
      sets were assessed for image quality sufficient for organ delineation and used to
      generate digitally-reconstructed radiographs (DRRs) (Pinnacle Workstation,
      Philips Healthcare). RESULTS: Each volunteer study took less than 10 minutes to
      complete, and the single acquisition required less than 3 minutes. Images from
      all four volunteers had excellent image quality sufficient for organ delineation
      and complete cortical bone segmentation. In addition, the DDRs for all four
      volunteers were sufficient for 2D patient matching. CONCLUSION: This study
      confirms the feasibility of using a single acquisition MRI as a sole imaging
      modality for treatment planning simulation in the brain. To validate this method,
      we plan to use this imaging protocol in a group of patients and compare the DRRs
      and dose plans with those acquired during CT simulation. Both authors are
      employees of Philips Healthcare.

PMID- 28519827
TI  - SU-E-J-79: Using the Distance of Closest Approach to Improve Compton Camera Image
      Quality.
AB  - PURPOSE: The prompt gamma radiation emitted from tissue during proton therapy
      offers a means of beam range verification. Compton camera (CC) imaging systems
      offer high efficiency and 3D imaging capability. However, Doppler broadening and
      the inaccuracies in the measurement of the scattering positions and energies
      reduce the image resolution. The purpose of our study is to determine if removing
      events with a distance-of-closest-approach greater than a threshold value will
      improve the resolution of images reconstructed using the stochastic origins
      ensemble (SOE) algorithm. METHODS: We first simulated a 3-stage CC detecting
      gammas from a 0.511 MeV point source. We then used SOE to reconstruct images from
      the point source and from a) all gammas, b) gammas with DCA < 3 mm, and c) gammas
      with DCA < 1 mm. We measured the point-spread-function for the point source for
      a), b), and c). Next, we simulated a 3-stage CC detecting prompt gammas emitted
      from tissue during proton therapy. We reconstructed the gammas using SOE and
      compared 2D images of all gammas, gammas with DCA < 3 mm, and gammas with DCA < 1
      mm. RESULTS: The FWHM of the PSF of the 0.511 MeV point source was reduced by 50%
      when DCA was required to be < 5 mm, and it was reduced by 65% when DCA was
      required to be < 3 mm. 2D images of a proton beam are of visibly higher quality
      as the DCA requirement is lowered. CONCLUSIONS: The DCA for MC events can be used
      to identify the events with significant resolution loss due to the detector
      effects. Removing these events before running the reconstruction algorithm
      results in higher quality images. We discuss methods to predict the DCA based on
      the measured scatter data, so that a similar technique can be applied to data
      from real detectors. This work was supported by the National Institutes of Health
      through award number R21CA137362 from the National Cancer Institute.

PMID- 28519828
TI  - SU-E-J-119: Comparative Evaluation of Respiratory Motion-Corrected Cone-Beam CT
      Images Derived from Treatment-Day Vs. Simulation-Day Respiration-Correlated CT
      Scans.
AB  - PURPOSE: Respiration-induced motion artifacts in cone-beam CT (CBCT) can be
      corrected using a model of patient motion obtained from respiration-correlated CT
      (RCCT). This approach assumes that respiration-induced organ deformations at
      simulation, when RCCT scans are normally acquired, are still valid at treatment.
      The purpose of this study is to compare lung tumor image quality in motion
      corrected CBCT images derived from treatment-day RCCT(tx) to simulation-day
      RCCT(sim) patient images. METHODS: In an IRB-approved study, lung cancer patients
      receive an RCCT at simulation, and an RCCT, gated CBCT and 1-minute CBCT at one
      treatment session. CBCT projections from the 1-minute scan are sorted according
      to breathing amplitude from an external monitor and reconstructed and warped to
      obtain a motion-corrected MC-CBCT at end expiration. Motion correction uses a
      model adapted from either RCCT(tx) or RCCT(sim), thus obtaining MC-CBCT(tx) and
      MC-CBCT(sim) images respectively. A gated CBCT, in which gantry rotation and
      projection acquisition occur within a gate at end expiration, serves as ground
      truth for comparison. Quality of MC-CBCT images is evaluated from tumor-to
      background contrast ratio (TBCR) values measured by delineating the tumor and
      annular volume around it on the gated CBCT then transferring the contours and
      aligning them to each MC-CBCT. RESULTS: TBCR is found tobe lower in MC-CBCT(sim)
      images, relative to MC-CBCT(tx), in four out of five patients with mean 21%
      reduction in a range 9-39%. In the remaining case, where there was no change in
      TBCR, tumor motion observed in the RCCT was small (2mm). Tumor motion extent
      relative to diaphragm is observed to change between RCCT(tx) and RCCT(sim) scans.
      CONCLUSIONS: Preliminary results indicate that deformation patterns in lung do
      change between simulation and treatment. Such variations may reduce the validity
      of using simulation data for motion-corrected CBCT at treatment. The findings
      require confirmation with larger numbers of patients. NIH/NCI award R01 CA126993,
      research grant from Varian Medical Systems.

PMID- 28519829
TI  - SU-E-J-89: Deformable Registration Method Using B-TPS in Radiotherapy.
AB  - PURPOSE: A novel deformable registration method for four-dimensional computed
      tomography (4DCT) images is developed in radiation therapy. METHODS: The proposed
      method combines the thin plate spline (TPS) and B-spline together to achieve high
      accuracy and high efficiency. The method consists of two steps. First, TPS is
      used as a global registration method to deform large unfit regions in the moving
      image to match counterpart in the reference image. Then B-spline is used for
      local registration, the previous deformed moving image is further deformed to
      match the reference image more accurately. RESULTS: Two clinical CT image sets,
      including one pair of lung and one pair of liver, are simulated using the
      proposed algorithm, which results in a tremendous improvement in both run-time
      and registration quality, compared with the conventional methods solely using
      either TPS or B-spline. CONCLUSIONS: The proposed method can combine the
      efficiency of TPS and the accuracy of B-spline, performing good adaptively and
      robust in registration of clinical 4DCT image.

PMID- 28519830
TI  - SU-E-J-100: Feasibility of Dose Calculation Using Combined Information of Cone
      Beam and Multi-Slice CT Images.
AB  - PURPOSE: The purpose of this study is to evaluate the feasibility of kilovoltage
      cone-beam CT (CBCT) images that are obtained with the Varian On-Board Imager in
      dose calculation at each radiation therapy. METHODS: CBCT images are commonly
      degraded by scattered radiations originating in the patient's body, and so the CT
      numbers of the CBCT images depend on data acquisition conditions and the patient
      size. However, the anatomical shape of each organ is not likely affected by
      scattered radiations, and so we used only the shape of major organs such as lungs
      and bones in the CBCT images, and replaced these CT numbers with those of the
      multi-slice CT (MSCT) images that were used for dose calculation in a treatment
      planning. As regards this alternative CT number we adopted the median of MSCT
      numbers in a segmented region of a major organ each corresponding to that in the
      CBCT images. We evaluated the validity of our segmented region (SR) method with
      images of eight patients with lung diseases. The number of irradiation beams was
      four. In this evaluation we used the distance-to-agreement (DTA) and y analysis,
      and the dose-volume-histogram (DVH) analysis. RESULTS: The pass rates of the DTA
      analysis (2mm) and gamma analysis (2mm, 2%) between the dose distributions
      calculated with our method were 90.4+/-6.0% and 99.1+/-1.1%, respectively. The
      results of the DVH analysis showed that the differences in doses (average,
      maximum and minimum) for a target volume were 1.3+/-0.5%, 0.9+/-0.8% and 3.4+/
      3.0%, respectively. These results showed that our method was acceptable in the
      calculation of a dose distribution. CONCLUSION: We evaluated the dose calculation
      method with a combination of CBCT and MSCT images. This method could yield an
      accurate dose distribution and achieved an easier verification of radiation
      therapy on each treatment day.

PMID- 28519831
TI  - SU-E-J-72: Design and Study of In-House Web-Camera Based Automatic Continuous
      Patient Movement Monitoring and Controlling Device for EXRT.
AB  - PURPOSE: The purpose of our study was to fabricate in-house web-camera based
      automatic continuous patient movement monitoring device and control the movement
      of the patients during EXRT. METHODS: Web-camera based patient movement
      monitoring device consists of a computer, digital web-camera, mounting system,
      breaker circuit, speaker, and visual indicator. The computer is used to control
      and analyze the patient movement using indigenously developed software. The
      speaker and the visual indicator are placed in the console room to indicate the
      positional displacement of the patient. RESULTS: Studies were conducted on
      phantom and 150 patients with different types of cancers. Our preliminary
      clinical results indicate that our device is highly reliable and can accurately
      report smaller movements of the patients in all directions. The results
      demonstrated that the device was able to detect patient's movements with the
      sensitivity of about 1 mm. When a patient moves, the receiver activates the
      circuit; an audible warning sound will be produced in the console. Through real
      time measurements, an audible alarm can alert the radiation technologist to stop
      the treatment if the user defined positional threshold is violated.
      Simultaneously, the electrical circuit to the teletherapy machine will be
      activated and radiation will be halted. CONCLUSIONS: Patient's movement during
      the course for radiotherapy was studied. The beam is halted automatically when
      the threshold level of the system is exceeded. By using the threshold provided in
      the system, it is possible to monitor the patient continuously with certain fixed
      limits. An additional benefit is that it has reduced the tension and stress of a
      treatment team associated with treating patients who are not immobilized. It also
      enables the technologists to do their work more efficiently, because they don't
      have to continuously monitor patients with as much scrutiny as was required.

PMID- 28519832
TI  - SU-E-J-111: Compute the Optimal Threshold for PET Functional Volume Delineation.
AB  - PURPOSE: To construct a method being able to compute the optimal threshold (OT)
      directly from PET images for functional volume delineation without any a priori
      information about scanners, imaging protocols and tumor size. METHODS: A
      mathematic model for partial volume effect (PVE) was analyzed for a spherical
      object with a constant activity imaged by a scanner with Gaussian point spread
      function (PSF). The theoretic analysis showed that information about some factors
      that are related to the PVE such as the PSF and tumor size had been actually
      embedded into PET images. We developed a new concept - the Optimal Area Ratio
      (OAR) that is a function of the object radius and can be derived from the model
      with some mathematic manipulations. With this new concept, information about PSF
      and tumor size can be recovered directly from PET images, and the OT can be
      calculated accordingly. The basic idea is to use the whole dynamic behavior (the
      behavior of the volume sizes due to different thresholds uniformly distributed in
      [0,1]) of a region-growing algorithm to find the OT. A computer simulation and
      experiments on phantoms with different object sizes and different noise levels
      were conducted to evaluate the above theoretic analysis. RESULTS: For the
      computer simulation, the calculated OT was exactly the real OT. In the
      experiments on phantoms, the calculated OT led to visually satisfactory
      delineation results. CONCLUSIONS: The new theoretic analysis showed that the OT
      can be calculated without any a priori information about scanners, imaging
      protocols and tumor size. The computer simulation and phantom experiments
      validated the theoretic analysis.

PMID- 28519833
TI  - SU-E-J-83: Improving Respiration-Gated IMRT Delivery Efficiency by Dual-Gating at
      Inhale and Exhale: Evaluation of Planning on Eclipse and the Need for Accurate
      Image Registration.
AB  - PURPOSE: Dual-gated intensity modulated radiation therapy (DG-IMRT) is a novel
      delivery method for speeding respiratory-gated IMRT delivery in which dose is
      delivered during both inhale and exhale windows. To determine the feasibility of
      designing DG-IMRT plans using current clinical treatment planning systems, we
      design and evaluate a lung patient plan using Eclipse. METHODS: Tumor target
      volumes were contoured on inhale and exhale CTs for a lung cancer patient with
      ~1mm motion. Separate 5-field IMRT plans were optimized in Eclipse for the inhale
      PTV on the inhale CT and for the exhale PTV on the exhale CT. The inhale plan
      dose was mapped to the exhale geometry using several deformable medical image
      registration methods, and the two doses were summed to produce the DG-IMRT dose.
      The accumulated dual-gated dose for the best performing registration is
      presented. RESULTS: Though the dual-gated inhale and exhale plans meet clinical
      requirements, the accumulated dual-gated dose performs quite poorly. Examination
      of the deformations indicates that only about two-thirds of the voxels within the
      inhale PTV map to voxels within the exhale PTV, indicating an unacceptably low
      level of physiological accuracy. CONCLUSION: It is possible to design dual-gated
      plans in Eclipse, but there is currently no accurate means of evaluated the
      summed dose. Furthermore, our results underscore the need for image registration
      methods that accurately model underlying tissue deformations before they can be
      used for dose accumulation in the presence of organ motion. This work was
      supported by the National Cancer Institute (T32 CA09695 - Glazer) and the
      National Institutes of Health (1RO1 CA 133474 - Xing).

PMID- 28519834
TI  - SU-E-J-93: Fourier Transform-Based Medical Image Registration.
AB  - PURPOSE: To evaluate the use of a Fast Fourier Transform (FFT) based pattern
      matching algorithm for two-dimensional translational and rotational medical image
      registration. METHODS: The FFT pattern matching algorithm is based on the Fourier
      shift theorem. Briefly, image registration is accomplished by obtaining the
      Fourier Transform (FT) of two images, taking the normalized cross-correlation of
      the two FT, and performing an inverse FT on this correlation matrix. This results
      in a Dirchlet delta function that has a maximum value at a location corresponding
      to the translational shift between the two images. Rotational registration can
      also be achieved by performing this algorithm on the polar transformation of the
      FT images. The FT registration method was evaluated through the use of clinical
      images with induced translational and rotational shifts. RESULTS: Over a range of
      induced shifts of +/-10 mm in both the x and y directions, and induced rotations
      of +/-10 degrees, all recovered rotations were within 0.1 degree of the induced
      rotation, and all recovered translations were within 0.5 mm of the induced
      translation. The computational time of the FT registration on a 1024*1024 image
      was approximately 2.23 sec. CONCLUSIONS: An FFT based image registration
      algorithm is computationally efficient and provides a high degree of accuracy for
      two dimensional image registrations. The FFT registration approach provides a
      distinct analytical solution and does not rely on iterative methods to converge
      on a solution. In addition, the discrete nature of the FFT means that the
      accuracy of the solution is directly related to the size of the pixels in the
      images. The equivalent of sub-pixel registration can be achieved by simply
      resizing the image to a larger matrix (i.e. 512*512 to 1024*1024).

PMID- 28519896
TI  - Sixtieth Annual Meeting of the Canadian Organization of Medical Physicists and
      the Canadian College of Physicists in Medicine.

PMID- 28519835
TI  - SU-E-J-64: Towards a Patient Specific Deformation Model in the Male Pelvis for
      IGRT via Limited Angle Imaging.
AB  - PURPOSE: To evaluate the feasibility of patient specific deformation models
      (PSDM) in the male pelvis for IGRT by limited angular imaging. METHODS: In IGRT
      via limited angular imaging, insufficient angular projections are acquired to
      uniquely determine a 3D attenuation distribution. For highly limited geometries,
      image quality may be too poor for successful non-rigid registration. This can be
      overcome by restricting the transformation space to one containing only feasible
      transformations learned from prior 3D images. This has been successfully applied
      in the lung region where a majority of deformation is due to respiratory motion
      which can be adequately observed at planning time with RCCT. Typically, the
      phases of the RCCT are registered together to form an group-wise mean image and
      transformations to each training image. PCA is then performed on the
      transformation displacement vector fields. The transformation is found at
      treatment time by registration of digitally reconstructed radiographs of the
      transformed image to the measured projections, optimizing over the parameters of
      the PCA subspace. In the male pelvis, deformation is much more complicated than
      respiratory deformation and is largely inter-fractional due to changes in bladder
      and rectal contents, articulation, and motion of the bowels. A similar model is
      developed for the male pelvis which takes into account pelvic anatomical
      information and handles the more complicated deformation space. RESULTS: Using
      the leave-one-out method, dice similarity coefficients in the prostate compared
      with manual segmentations are increased over the those obtained by rigid
      registration and are comparable with those obtained by 3D non-rigid registration
      methods. CONCLUSIONS: This method produces better results than rigid registration
      and is comparable with results obtained by 3D/3D registration even though it uses
      limited angle projections. However, its relies on daily training CTs, so it is
      not yet a viable clinical method. Funding provided in part by Siemens Medical.

PMID- 28519898
TI  - Evaluating the effect of a year-long film focused environmental education program
      on Ugandan student knowledge of and attitudes toward great apes.
AB  - Films, as part of a larger environmental education program, have the potential to
      influence the knowledge and attitudes of viewers. However, to date, no
      evaluations have been published reporting the effectiveness of films, when used
      within primate range countries as part of a conservation themed program. The
      Great Ape Education Project was a year-long environmental education program
      implemented in Uganda for primary school students living adjacent to Kibale
      National Park (KNP) and Bwindi Impenetrable National Park (BINP). Students viewed
      a trilogy of conservation films about great apes, produced specifically for this
      audience, and participated in complementary extra-curricular activities. The
      knowledge and attitudes of students participating in the program from KNP, but
      not BINP were assessed using questionnaires prior to (N = 1271) and following (N
      = 872) the completion of the program. Following the program, students
      demonstrated a significant increase in their knowledge of threats to great apes
      and an increase in their knowledge of ways that villagers and students can help
      conserve great apes. Additionally, student attitudes toward great apes improved
      following the program. For example, students showed an increase in agreement with
      liking great apes and viewing them as important to the environment. These data
      provide evidence that conservation films made specifically to address regional
      threats and using local actors and settings can positively influence knowledge of
      and attitudes toward great apes among students living in a primate range country.

PMID- 28519899
TI  - Hepatic AA amyloidosis in a cat: cytologic and histologic identification of AA
      amyloid in macrophages.
AB  - A 3-year-old, spayed female, Domestic Shorthair cat presented with anorexia,
      lethargy, vomiting, probable hemoabdomen, and multiple masses on the right
      lateral liver lobe. Clinicopathologic and imaging abnormalities included anemia,
      azotemia, icterus, and hepatomegaly with hypoechoic masses. On cytologic
      evaluation of a fine-needle aspiration of a liver mass there was abundant
      extracellular pink- to purple-colored material between hepatocytes. The amorphous
      material was stained with direct fast scarlet (DFS), and green birefringent areas
      were observed under polarized light, confirming the presence of amyloid. A unique
      finding on the cytologic smear were macrophages containing amorphous and
      fibrillar amyloid-like protein. Histopathologic examination using H&E and Congo
      red staining confirmed amyloid deposits within the space of Disse, along the
      sinusoids, portal tracts, blood vessel walls, and within the cytoplasm of
      macrophages. Immunohistochemical staining with anti-AA amyloid antibodies further
      confirmed the presence of AA amyloid. To the author's knowledge, this is the
      first report of the cytologic finding of AA amyloid protein within macrophages
      and DFS stain detection of amyloid on a cytologic smear.

PMID- 28519900
TI  - Type I interferon pathway in CNS homeostasis and neurological disorders.
AB  - Type I interferons (IFNs), IFN-alpha and IFN-beta, represent the major effector
      cytokines of the host immune response against viruses and other intracellular
      pathogens. These cytokines are produced via activation of numerous pattern
      recognition receptors, including the Toll-like receptor signaling network,
      retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated
      protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the
      contribution of type I IFNs to peripheral immunity is well documented, they can
      also be produced by almost every cell in the central nervous system (CNS).
      Furthermore, IFNs can reach the CNS from the periphery to modulate the function
      of not only microglia and astrocytes, but also neurons and oligodendrocytes, with
      major consequences for cognition and behavior. Given the pleiotropic nature of
      type I IFNs, it is critical to determine their exact cellular impact.
      Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene
      expression have been linked to several CNS diseases termed "interferonopathies"
      including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)
      deficiency. In contrast, in the CNS of mice with virus-induced neuroinflammation,
      type I IFNs can limit production of other cytokines to prevent potential damage
      associated with chronic cytokine expression. This capacity of type I IFNs could
      also explain the therapeutic benefits of exogenous type I IFN in chronic CNS
      autoimmune diseases such as multiple sclerosis. In this review we will highlight
      the importance of a well-balanced level of type I IFNs for healthy brain
      physiology, and to what extent dysregulation of this cytokine system can result
      in brain 'interferonopathies'.

PMID- 28519901
TI  - Inhibition of soil microbial activity by nitrogen-based energetic materials.
AB  - We investigated individual toxicities of the nitrogen-based energetic materials
      (EMs) 2,4-dinitrotoluene (2,4-DNT); 2-amino-4,6-dinitrotoluene (2-ADNT); 4-amino
      2,6-dinitrotoluene (4-ADNT); and nitroglycerin (NG) on microbial activity in
      Sassafras sandy loam (SSL) soil, which has physicochemical characteristics that
      support very high qualitative relative bioavailability for organic chemicals.
      Batches of SSL soil for basal respiration (BR) and substrate-induced respiration
      (SIR) assays were separately amended with individual EMs or acetone carrier
      control. Total microbial biomass carbon (biomass C) was determined from CO2
      production increases after addition of 2500 mg/kg of glucose-water slurry to the
      soil. Exposure concentrations of each EM in soil were determined using US
      Environmental Protection Agency method 8330A. Basal respiration was the most
      sensitive endpoint for assessing the effects of nitroaromatic EMs on microbial
      activity in SSL, whereas SIR and biomass C were more sensitive endpoints for
      assessing the effects of NG in soil. The orders of toxicity (from greatest to
      least) were 4-ADNT > 2,4-DNT = 2-ADNT > NG for BR; but for SIR and biomass C, the
      order of toxicity was NG > 2,4-DNT > 2-ADNT = 4-ADNT. No inhibition of SIR was
      found up to and including the greatest concentration of each ADNT tested in SSL.
      These ecotoxicological data will be helpful in identifying concentrations of
      contaminant EMs in soil that present acceptable ecological risks for biologically
      mediated processes in soil. Environ Toxicol Chem 2017;36:2981-2990. Published
      2017 Wiley Periodicals Inc. on behalf of SETAC.This article is a US government
      work and, as such, is in the public domain in the United States of America.

PMID- 28519903
TI  - Functional neuroimaging offers insights into delirium pathophysiology: A
      systematic review.
AB  - OBJECTIVE: This systematic review describes the current functional neuroimaging
      literature in delirium, discusses pathophysiological implications of these
      results and highlights areas for further study. METHODS: In accordance with
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, an
      extensive search of medical databases was undertaken, identifying eighteen
      studies of variable quality and design suitable for inclusion. RESULTS:
      Functional neuroimaging has highlighted significant abnormalities during
      delirium, with disturbances in cerebral haemodynamics and functional connectivity
      potentially playing a key role in delirium pathophysiology. CONCLUSIONS: Although
      employing functional neuroimaging in delirium remains difficult, these findings
      demonstrate the potential of functional imaging to increase our understanding of
      the underlying mechanisms of delirium, to lead to more efficient interventions
      and targeted therapies and to reduce the burden of this underdiagnosed syndrome.

PMID- 28519963
TI  - Shift in paradigm of clinical management of anastomotic leak?

PMID- 28519902
TI  - Reduced gliotransmitter release from astrocytes mediates tau-induced synaptic
      dysfunction in cultured hippocampal neurons.
AB  - Tau is a microtubule-associated protein exerting several physiological functions
      in neurons. In Alzheimer's disease (AD) misfolded tau accumulates intraneuronally
      and leads to axonal degeneration. However, tau has also been found in the
      extracellular medium. Recent studies indicated that extracellular tau uploaded
      from neurons causes synaptic dysfunction and contributes to tau pathology
      propagation. Here we report novel evidence that extracellular tau oligomers are
      abundantly and rapidly accumulated in astrocytes where they disrupt intracellular
      Ca2+ signaling and Ca2+ -dependent release of gliotransmitters, especially ATP.
      Consequently, synaptic vesicle release, the expression of pre- and postsynaptic
      proteins, and mEPSC frequency and amplitude were reduced in neighboring neurons.
      Notably, we found that tau uploading from astrocytes required the amyloid
      precursor protein, APP. Collectively, our findings suggests that astrocytes play
      a critical role in the synaptotoxic effects of tau via reduced gliotransmitter
      availability, and that astrocytes are major determinants of tau pathology in AD.

PMID- 28519965
TI  - Micellar electrokinetic chromatography fingerprinting combined with chemometrics
      as an efficient strategy for evaluating the quality consistency and predicting
      the antioxidant activity of Lianqiao Baidu pills.
AB  - An approach combining micellar electrokinetic chromatography fingerprinting with
      chemometrics was developed to evaluate the quality consistency of Lianqiao Baidu
      pills, which are traditional Chinese patent medicines composed of 19 herbs used
      mainly to treat skin ulcers, common cold, rheumatism, herpes, and constipation.
      The triangle optimization method was employed to choose a satisfactory background
      electrolyte, with the information index, I, as an objective function for
      assessing the capillary electrophoresis conditions. Then, under the optimal
      conditions, the micellar electrokinetic chromatography fingerprints of 28 batches
      of samples were established, and five marker compounds were quantitatively
      determined simultaneously. A limited-ratio quantified fingerprint method was
      introduced to evaluate the chromatographic fingerprints both qualitatively and
      quantitatively. Principle component analysis revealed that the 28 batches of
      samples can be clustered according to different manufacturers. Moreover, the
      relationship between the fingerprint and the antioxidant activity was explored by
      orthogonal partial least-squares regression, which provided critical medicinal
      efficacy information for quality control. The present study establishes a
      powerful and reliable method for monitoring the quality consistency of Lianqiao
      Baidu pill.

PMID- 28519967
TI  - WE-D-218-01: Ultrasound Scanner Innovations and Clinical Practice.
AB  - : Of all the imaging modalities, ultrasound scanners have gone through the most
      profound changes over the last several decades in terms of their size,
      capability, and cost. Much of this is due to the small data acquisition devices
      (ultrasound transducers) and Moore's Law dependent signal/image processors that
      comprise and ultrasound scanner. These are in direct contrast with the front ends
      of MRI or CT scanners with their sizeable power hungry gantries. Thus ultrasound
      has been a direct beneficiary of the miniaturization associated with the
      semiconductor industry; this has enabled the migration of much hardware
      functionality to software and development of much smaller devices even including
      handheld scanners. Such changes are having a significant impact on clinical
      utilization of ultrasound. This talk will review some of these including the
      recent introduction of complete software backends, i.e. ultrasound scanners
      composed of analog front ends which are connected to processors with minimal
      dedicated digital hardware. LEARNING OBJECTIVES: 1. Understand the architecture
      of an ultrasound scanner and how it has changed with evolving technology. 2.
      Understand the implications to clinical practice from these changes. 3.
      Understand the possibilities for the future of ultrasound scanners both from the
      view of new technical capabilities and how these might impact the clinic.

PMID- 28519964
TI  - Association between serum 25-hydroxyvitamin D and glycated hemoglobin levels in
      type 2 diabetes patients with chronic kidney disease.
AB  - AIMS/INTRODUCTION: Vitamin D is suggested to influence glucose homeostasis. An
      inverse relationship between serum 25-hydroxyvitamin D (25[OH]D) and glycemic
      control in non-chronic kidney disease (CKD) patients with type 2 diabetes was
      reported. We aimed to examine this association among type 2 diabetes patients
      with CKD. MATERIALS AND METHODS: A total of 100 type 2 diabetes participants with
      stage 3-4 CKD were recruited. Blood for glycated hemoglobin (HbA1c ), serum
      25(OH)D, renal and lipid profiles were drawn at enrollment. Correlation and
      regression analyses were carried out to assess the relationship of serum 25(OH)D,
      HbA1c and other metabolic traits. RESULTS: A total of 30, 42, and 28% of
      participants were in CKD stage 3a, 3b and 4, respectively. The proportions of
      participants based on ethnicity were 51% Malay, 24% Chinese and 25% Indian. The
      mean (+/-SD) age and body mass index were 60.5 +/- 9.0 years and 28.3 +/- 5.9
      kg/m2 , whereas mean HbA1c and serum 25(OH)D were 7.9 +/- 1.6% and 37.1 +/- 22.2
      nmol/L. HbA1c was negatively correlated with serum 25(OH)D (rs = -0.314, P =
      0.002), but positively correlated with body mass index (rs = 0.272, P = 0.006)
      and serum low-density lipoprotein cholesterol (P = 0.006). There was a
      significant negative correlation between serum 25(OH)D and total daily dose of
      insulin prescribed (rs = -0.257, P = 0.042). Regression analyses showed that
      every 10-nmol/L decline in serum 25(OH)D was associated with a 0.2% increase in
      HbA1c . CONCLUSIONS: Lower serum 25(OH)D was associated with poorer glycemic
      control and higher insulin use among multi-ethnic Asians with type 2 diabetes and
      stage 3-4 CKD.

PMID- 28519966
TI  - Understanding the relationship between olfactory-specific quality of life,
      objective olfactory loss, and patient factors in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) significantly impacts olfaction.
      However, the relationship between objective olfaction and patient-reported
      olfactory-specific quality of life (QOL) is not well understood. Furthermore,
      objective olfactory testing can be time consuming, so we sought to determine if
      patient-reported olfactory QOL can be used as screening tool for olfactory
      dysfunction. METHODS: Olfactory dysfunction was evaluated in 109 patients with
      CRS using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS)
      and the Sniffin' Sticks Test, assessing for olfactory threshold, discrimination,
      identification, and overall composite scores (TDI; composite score of threshold,
      discrimination, and identification). Regression analysis was performed to
      correlate olfactory metrics and patient and disease-specific factors with QOD-NS
      scores. Optimal QOD-NS scores to classify patients based upon objective olfactory
      function were established. RESULTS: Bivariate and multivariate regression
      analyses of QOD-NS and CRS-associated comorbidities, objective measures of
      disease, demographics, and CRS-specific QOL were performed. Non-white race,
      depression, and worse 22-item Sino-Nasal Outcome Test (SNOT-22) scores correlated
      with worse QOD-NS scores (p < 0.005). Worse TDI scores correlated with worse QOD
      NS scores, and discrimination had the strongest correlation (p < 0.001). Mean +/-
      standard deviation (SD) QOD-NS scores for normosmia, hyposmia, and anosmia were
      44 +/- 7.2, 35.7 +/- 12.8, and 31.6 +/- 10.7, respectively. Receiver operating
      characteristic curve analysis revealed an area under the curve of 0.770 (p <
      0.001), and a QOD-NS cutoff of 38.5 to have maximal Youden's index to define
      normal vs abnormal TDI score. CONCLUSION: In CRS, QOD-NS correlates with non
      white race, depression, SNOT-22, and TDI score, with discrimination having the
      strongest correlation. The QOD-NS also appears to be a feasible tool for
      olfaction screening.

PMID- 28519968
TI  - WE-E-BRB-06: Monte Carlo Calculations of the Skin Dose for Longitudinal Linac-MR
      System Using Realistic Three-Dimensional Magnetic Field Modeling.
AB  - PURPOSE: This study quantifies the effects of the magnetic field of a
      longitudinal linac-MR system (B-field parallel to beam direction) on skin dose
      due to the confinement of contaminant electrons, using Monte Carlo calculations
      and realistic 3-D models of the magnetic field. METHODS: The complete realistic 3
      D magnetic fields generated by the bi-planar Linac-MR magnet assembly are
      calculated with the finite element method using Opera- 3D. EGSnrc simulations are
      performed in the presence of ~0.6T and IT MRI fields that have realistic rapid
      fall-off of the fringe field. The simulation geometry includes a Varian 600C 6MV
      linac, the yoke and magnetic shields of the MRIs, and features an isocentre
      distance of 126 cm. Phase spaces at the surface of a water phantom are scored
      using BEAMnrc; DOSXYZnrc is used to score the resulting CAX percent depth-doses
      in the phantom and the 2D skin dose distributions in the first 70 urn layer. For
      comparison, skin doses are also calculated in the absence of magnetic field and
      using a 1-D magnetic field with an unrealistic fringe field. The effects of field
      size and air gap (between phantom surface and magnet pole) are also examined.
      RESULTS: Analysis of the phase-space and dose distributions reveals that
      significant containment of electrons occurs primarily close to the uniform
      magnetic field region. The increase in skin dose due to the magnetic field
      depends on the air gap, varying from 1% to 13% for air gaps of 5 to 31 cm,
      respectively. The increase is also field-size dependent, varying from 3% at 20*20
      cm2 to 11% at 5*5 cm2. CONCLUSIONS: Calculations based on various realistic MRI
      3D magnetic-field maps that appropriately account for the rapid decay of the
      fringe field show that the increase in the patient skin dose of a longitudinal
      Linac-MR system is clinically insignificant.

PMID- 28519969
TI  - WE-C-217BCD-03: Restricted Data Set Reconstruction Based on Respiration Quality
      to Improve Prospectively Gated in Vivo Micro-CT of Mice.
AB  - PURPOSE: Micro-CT is commonly employed for lung imaging of mice; prospective
      gating allows for in-vivo imaging of free-breathing subjects. While this
      technique is successfully executed for healthy animals, results are less
      consistent for some disease models whose symptoms include irregular or unstable
      respiration. The purpose of this work is to repair the quality of high-blur
      images that arise from respiration instability using a retrospective method of
      motion reduction which identifies the individual x-ray projection images
      contributing most to the motion blur. Reconstructions were performed after the
      exclusion of these projections (the so-called restricted set). METHODS: Sixteen
      mice were imaged using field emission cone beam micro-CT and prospective gating
      with a bellows-type respiration sensor. The scanner was operated in step-and
      shoot mode; 400 projection images were acquired per scan. An algorithm was
      developed to analyze the respiration trace file and segment the individual breath
      corresponding to each projection image. We tested three different criteria to
      define a bad breath shape (correlation, mean breath height, or mode breath
      height), and restricted data set reconstructions were performed using each of
      these criteria to exclude projections corresponding to bad breaths. Each
      restricted set was compared against the full unrestricted data set image; the
      slope perpendicular to the diaphragm was used as a quantitative assessment of
      motion blur. RESULTS: All image sets saw a reduction in motion blur with at least
      one restriction technique. In 22 of 27 images, improvement was measured
      regardless of the removal criterion. Five percent total projection removal is
      optimal; a more aggressive correction increases the likelihood of under-sampling
      artifacts. CONCLUSIONS: Removing a subset of bad projections from otherwise
      complete image sets measurably decreases motion blur in respiratory-gated
      imaging. An approach based on breath height generally provides the best results.
      The technique is applicable to a variety of imaging modalities.

PMID- 28519971
TI  - WE-E-BRB-08: Establishing Comprehensive Quality Assurance Program for Volumetric
      Modulated Arc Therapy - Clinical Study Using Control Point Analysis Software.
AB  - PURPOSE: to validate the clinical effectiveness of Control Point Analysis (CPA)
      software and establish a comprehensive quality assurance (QA) program for
      Volumetric Modulated Arc Therapy (VMAT) treatment. METHODS: The comparison and
      gamma analysis of ArcCHECKTM measurement and treatment planning system (TPS) is
      considered one of the common methods for VMAT QA procedure. However, questions
      like 'how QA discrepancies affect patient treatment? and ? what are the sources
      of discrepancies? cannot be answered. In this study, 3DVHTM and recently
      developed CPA software were tested for eight cases, including prostate, brain,
      head&neck, and TGI 19 phantom cases. All VMAT plans used two arcs, with various
      settings of couch rotation, collimator rotation, and splitting fields. Each
      single arc was equally divided into 24 sub-arcs and doses of sub-arcs were
      exported for CPA analysis. Gamma analyses (3mm/3%) were compared using the
      ArcCHECK dose, single arc doses, sub-arc doses, and 3DVH patient's dose estimated
      by Planned Dose PerturbationTM (PDP) algorithm. RESULTS: ArcCHECK composite dose
      analyses were consistent with CPA sub-arc analysis for most cases. 3DVH generally
      showed higher passing rate in dose voxel-by-voxel comparison. Cases with failed
      QA were further analyzed by CPA for each sub-arc to reveal the sources of dose
      discrepancies, whether they are mechanical errors (i.e. leaf motion failure) or
      dosimetric modeling errors (i.e. elongated beam spot size or incorrect dynamic
      leaf gap). CPA analysis showed values for cases with passed QA to detect small
      discrepancies caused by failed MLC which was otherwise smeared out in the
      composite dose comparison. CONCLUSIONS: CPA analysis expands QA process to a
      greater level of details without additional work by users. With the additions of
      CPA analysis and 3DVHTM, one can establish a comprehensive VMAT QA program with
      detailed mapping of composite dose passing rate, the estimated effect of
      discrepancies on patients, and possible sources of discrepancies.

PMID- 28519970
TI  - WE-E-213CD-03: Inverse-Consistent Symmetric Registration of Inner Colon Surfaces
      Derived from Prone and Supine CT Colonography.
AB  - PURPOSE: Robust registration of prone and supine colonie surfaces acquired during
      CT colonography may lead to faster and more accurate detection of colorectal
      cancer and polyps. Any directional bias when registering one surface to the other
      could precipitate incorrect anatomical correspondence and engender reader error.
      Despite this, non-rigid registration methods are often implemented
      asymmetrically, which could negatively influence the registration. We aimed to
      reduce directional bias and so increase robustness by adapting a cylindrical
      registration algorithm to be both symmetric and inverse-consistent. METHODS: The
      registration task can be simplified by mapping both prone and supine colonie
      surfaces onto regular cylinders. Spatial correspondence can then be established
      in cylindrical space using the original surfaces' local shape indices. We
      implemented a symmetric formulation of the popular non-rigid B-spline image
      registration method in cylindrical space. A symmetric similarity measure computes
      the sum of squared differences between both cylindrical representations of prone
      to-supine and supine-to-prone directions simultaneously. Inverse consistency of
      the transformation is enforced by adding an appropriately weighted penalty term
      to the optimisation function. RESULTS: We selected 8 CT colonography patient
      cases with marked variation in luminal distension and surface morphology. We
      randomly allocated 4 of these for tuning an optimal set of registration
      parameters and 4 for validation. The mean inverse-consistency error was reduced
      by 32% from 4.8mm to 3.2mm by the new symmetric formulation. The mean
      registration error improved from 8.2mm to 7.3mm for 330 manually chosen reference
      points on the 4 validation sets. CONCLUSIONS: A symmetric formulation of prone
      and supine surface registration improves the quality of registration. Information
      from both prone-to-supine and supine-to-prone directions helps enforce
      convergence towards a more accurate solution due to reduced directional bias. A
      more robust and accurate registration will facilitate interpretation of CT
      colonography and has the potential to improve existing computer-aided detection
      methods. The authors gratefully acknowledge financial support for this work from
      the NIHR program: a?oeImaging diagnosis of colorectal cancer: Interventions for
      efficient and acceptable diagnosis in symptomatic and screening populationsa?.

PMID- 28519972
TI  - WE-C-217BCD-05: A Novel Interpolation Method for the 3D Reconstruction of Cell
      Structures.
AB  - PURPOSE: To develop a new interpolation method for accurate 3D reconstruction of
      cell morphology from laser scanning confocal microscope (LSCM) image data.
      METHODS: Current techniques are based on the assumption that pixel intensity or
      contour shapes of images change linearly in the interpolation direction. Gray
      value and position of the pixel in interpolated image slice are obtained through
      weighted average calculation with gray-values and distances of corresponding
      pixels in two adjacent original image slices, only information from adjacent
      image slices is considered, often fail to meet the need of 3D reconstruction for
      cells because of the complex cell morphology. The new method interpolates
      cellular organelle contours in polar coordinate system. Coordinate system origin
      is chosen to be the mass center weighted by pixel intensity instead of
      conventional geometric center, contour points of the organelle is sampled by
      their angles first and fitted with uniform cubic B-spline to perform
      interpolation. For complex organelle structures such as branched nuclei, a
      special method combining morphological information and corner detection technique
      based on curvature scale space has been developed to solve the contour division
      and related problems. New method was applied to confocal images of 130 different
      cells acquired with an LSCM system (LSM510, Zeiss), sampling step was set as 0.5
      MUm in longitudinal direction, pixel size in horizontal plane was 0.07 MUm and
      the resolution was 512*512. Marching cubes algorithm was used for 3D
      reconstruction. RESULTS: Experiments showed that reconstructed 3D images with new
      method have much smoother and more valid organelle surfaces for both cytoplasm
      and nucleus than those from conventional methods. CONCLUSIONS: The new
      interpolation method can significantly improve the quality of 3D reconstruction
      and serve as a valid and effective tool for quantitative study of 3D cell
      morphology in radiation biology and other areas of life science.*support by NSFC-
      81171342. Supported by the National Science Foundation of China (NSFC- 81171342).

PMID- 28519973
TI  - WE-E-213CD-05: A Non-Rigid Image Registration Algorithm That Accommodates Organ
      Segmentation Error.
AB  - PURPOSE: To introduce a new deformable image registration algorithm based on
      surface matching that accommodates organ delineation error in daily Cone-beam CT
      images based on a priori knowledge of inter-observer segmentation uncertainty.
      METHODS: The dataset includes four prostate cancer patients who underwent primary
      external beam radiotherapy and had tumors that were confined to the prostate. All
      imaging was performed without intravenous contrast. Organ surface segmentation
      errors in a multiple observer-contouring study on the pelvic organs in Fan-beam
      CT (FBCT) and Cone-beam CT (CBCT) were estimated from the training dataset. A
      novel deformable image registration algorithm is presented where the organ
      surface matching is penalized by this error. Portions of the organ surface that
      are delineated reliably are used to guide the registration whereas the portions
      that are highly uncertain are ignored. This approach reduces the impact of
      delineation errors in CBCT. An evaluation experiment compares three algorithms,
      namely intensity-only registration (INT), equally-weighted surface and image
      registration (EWSIR) and the proposed uncertainty- weighted surface and image
      registration. RESULTS: The surface dissimilarity was reduced from 0.172 to 0.134,
      0.043 and 0.044 respectively after registration. The Jacobian of the
      transformation found by the proposed method was closer to one than that of EWSIR
      in the prostate. CONCLUSIONS: In prostate external-beam radiotherapy, slice-by
      slice 2D manual contouring has variable spatial accuracy. For deformable image
      registration methods that match segmented surfaces, regions of high inaccuracy
      can misguide the registration. In contrast to the image registration methods
      where the FBCT and CBCT surfaces (or other features) are assumed to be exact, our
      method takes this uncertainty into account. Preliminary results show an improved
      registration performance suggesting a potential use in IGRT. This work was
      supported by National Cancer Institute Grant No. P01 CA 116602.

PMID- 28519974
TI  - WE-C-217A-04: An Analysis of Recent Literature Regarding Radiation Risk.
AB  - The peer review process screens scientific articles for merit prior to acceptance
      or rejection for publication. After publication the process continues with
      scrutiny by other researchers as expressed in letters to the editor and other
      scientific research that either affirms or denies findings. Research into
      radiation effects directly affects the use of ionizing radiations in medicine.
      The quality of peer review of articles on radiation effects is therefore critical
      to the practice of medicine. This presentation will examine adequacy of peer
      review regarding recent articles on radiation effects that have appeared in the
      peer-reviewed literature. The purpose is to examine what factors in research
      techniques and analyses contribute to the quality and believability of the
      findings. Learning Objectives 1. To gain insight into the critical evaluation of
      scientific literature on bio effect s 2. To understand how to distinguish
      causation from correlation or association.

PMID- 28519975
TI  - WE-E-218-01: Writing and Reviewing Papers in Medical Physics.
AB  - : There is an art to writing a scientific paper so that it communicates
      accurately, succinctly, and comprehensively. Developing this art comes with
      experience, and sharing that experience with younger physicists is an obligation
      of senior scientists, especially those with editorial responsibilities for the
      journal. In this workshop, the preparation of a scientific manuscript will be
      dissected so participants can appreciate how each part is developed and then
      assembled into a complete paper. Then the review process for the paper will be
      discussed, including how to examine a paper and write an insightful and
      constructive review. Finally, we will consider the challenge of accommodating the
      concerns and recommendations of a reviewer in preparing a revision of the paper.
      A second feature of the workshop will be a discussion of the process of
      electronic submission of a paper for consideration by Medical Physics. The web
      based PeerX-Press engine for manuscript submission and management will be
      examined, with attention to special features such as epaps and line-referencing.
      Finally, new features of Medical Physics will be explained, such as Vision 20/20
      manuscripts, Physics Letters and the standardized formatting of book reviews.
      LEARNING OBJECTIVES: 1. Improve the participants' abilities to write a scientific
      manuscript. 2. Understand the review process for Medical Physics manuscripts and
      how to participate in and benefit from it. 3. Appreciate the many features of the
      PeerX-Press electronic management process for Medical Physics manuscripts. 4.
      Develop a knowledge of new features of Medical Physics.

PMID- 28519976
TI  - WE-E-BRB-01: A Mathematical Model of the Optical Density Growth of EBT2 Film
      after Proton Irradiation.
AB  - PURPOSE: Gafchromic EBT2 is being used for radiation dosimetry including photon,
      electrons and recently in proton beams, based on its color changes from
      transparent to blue due to polymerization. It is critical to understand the
      temporal response of the polymerization after irradiation to proton beam for more
      accurate dosimetric results with EBT2. METHODS: Five small pieces cut from the
      same sheet (lot no. A08060905A) were irradiated with different doses (2 - 10 Gy)
      using a clinical proton beam with range 16 cm and spread-out-Bragg-peak 10 cm. An
      EPSON flatbed 10000XL was used for digitization in 48 bit color RGB images. The
      films were kept in the same position on the scanner for each scan. Within a 6-day
      period, measurements were taken every 3 minutes for the first hour, every 5 to 30
      minutes for the first 1-12 hours and then randomly after 12 hours. Red, green and
      blue frequency read out of the scanner for each film was analyzed in ImageJ
      software. RESULTS: A mathematical function (netOD =a + beta (1-exp (-t/Ta)) +
      gamma (1-exp (-t/Tb)) was used to describe the temporal response. The
      polymerization is time dependent with two time constants, Ta (25 minutes) and Tb
      (1000 minutes), a, beta, and gamma are dose dependent parameters. The percentage
      of OD change per 10 minutes remains less than 1% after the first hour. A 7%-ll%
      increase in the net OD was observed within the first 12 h when irradiated within
      10 Gy, comparable to the 9% reported for EBT films. CONCLUSIONS: The growth of OD
      post-irradiation may be explained by the rapid polymerization in EBT2 film. This
      characteristic can be described by a double exponential function which may be
      used to correct the temporal coloration effect to improve the accuracy for
      radiation dosimetry using EBT2 film in proton beam.

PMID- 28519977
TI  - WE-E-BRA-01: Introduction to Treatment Assessment of Radiation Therapy Using MR
      Functional Imaging and Its Application to Intracranial Stereotactic Radiosurgery.
AB  - : Recent developments in MRI have substantially improved its performance, making
      it a potentially powerful tool for not only diagnosis but also therapy. Treatment
      assessment using MR functional imaging is the process of using MR functional
      imaging before and/or during and/or after a course of radiation therapy (RT) to
      assess treatment responses and as such to optimize therapeutic outcome. Various
      MR functional techniques including, but not limited to, diffusion weighted
      imaging (DWI), diffusion tensor imaging (DTI), MR spectroscopy (MRS) and dynamic
      contrast enhanced (DCE) imaging, have been investigated to assess therapeutic
      outcome in radiotherapy. DCE-MRI uses fast imaging and contrast material to
      assess changes in the microvascular environment. MRS can be used to assess non
      invasively biochemical changes caused by RT. Diffusion imaging techniques are
      used to assess the changes of cellular density and neural fibers caused by RT. In
      this lecture, the application of functional imaging to the assessment of
      stereotactic radiosurgery is illustrated. Stereotactic radiosurgery (SRS) is
      effective in treating brain tumors, but radiation may cause injury to normal
      brain tissues (e.g., white matter), compromising sensory and neurocognitive brain
      functions. DTI can be used to track neural fibers and assess radiation-induced
      damages in white matter. Furthermore, DCE-MRI can be used to interrogate tumor
      biology and treatment-related changes in tumor vasculature after SRS. These
      Issues related to treatment-related changes will be discussed. This lecture will
      provide an overview of the MR functional imaging along with its application to
      the assessment of stereotactic radiosurgery. LEARNING OBJECTIVES: 1. Understand
      the principles of MR functional imaging techniques 2. Understand the issues
      related to MR functional imaging 3. Understand the clinical application of MR
      functional imaging in assessing treatment response of SRS.

PMID- 28519978
TI  - WE-C-217BCD-09: Compressed Sensing in PET Imaging with Partial Detector Rings.
AB  - PURPOSE: Investigate the possibility of reducing the number of PET detector
      elements per ring (introduce gaps) while maintaining image quality by employing
      compressed sensing techniques. METHODS: A uniform Ge-68 phantom was imaged on a D
      RX PET/CT scanner twice; once with all detectors operational (baseline) and once
      with 8 equidistant detector blocks turned off (partially sampled [PS], 11%
      detectors off. The resulting PS sinogram was then decomposed in two different
      components, each sparsely represented in a specific transform domain. An
      iterative optimization technique was then used to recover the PS sinogram based
      on the solution of a combination of underdetermined system of equations and block
      coordinated relaxations. In addition, the total variation is minimized for the
      first component to direct it into a piece-wise smooth model. Finally the two
      components were summed to obtain the sinogram which was used to compare with the
      original PS sinogram. Comparison was done only for existing sinogram pixel
      values. This process was repeated iteratively until a RMS error of 5% or a total
      of 100 iterations were reached. For each iteration update, the values of the
      pixels corresponding to the missing detectors were obtained from the previous
      iteration while the remaining pixel values were extracted from the baseline
      sinogram. The resultant corrected sinograms where then reconstructed using OSEM
      and FBP and the corresponding images for full and PS sinograms were compared
      using mean and max activity concentration in a ROI placed centrally over the
      phantom. RESULTS: For OSEM (FBP) reconstruction, the mean and max activity
      concentration difference were -0.06% (-0.02%) and 3.7% (5.5%) respectively when
      compared to baseline. CONCLUSIONS: Compressed sensing seems to have the ability
      to recover PS PET data. Such an approach can potentially be used to generate PET
      images with accurate quantitation while reducing number of detectors/ring.

PMID- 28519979
TI  - WE-E-213CD-09: Multi-Atlas Fusion Using a Tissue Appearance Model.
AB  - PURPOSE: To improve multi-atlas based auto-segmentation by integrating a tissue
      appearance model with the Simultaneous Truth and Performance Level Estimation
      (STAPLE) algorithm to perform multi-atlas fusion. METHODS: Ten head-and-neck
      planning CT images were acquired (resolution: 1.0*1.0*2.5mm3 ) and the parotid
      glands were contoured manually by a head-and-neck oncologist. We performed 10
      leave-one-out tests by using one patient as test patient and the rest of 9
      patients as atlases. Deformable registration was first applied to transform the
      atlas parotid contours to the test image one by one. The STAPLE algorithm was
      initialized by a parotid tissue appearance model, which was estimated from the
      test image and encoded the intensity information of parotid glands. The
      individual deformed contours were then fused using the STAPLE algorithm to
      produce a best approximation of the true contour. The tissue appearance model was
      also applied to a deformable model segmentation to further refine the fused
      contours. RESULTS: The multi-atlas fusion using the tissue appearance model
      produced an average Dice coefficient of 85.2%+/-3.1% (left parotid) and 84.9%+/
      3.9% (right parotid) over the 10 tests between the auto-contour and the manual
      contour, and an average mean surface distance of 1.6+/-0.3mm and 1.6+/-0.4mm for
      left and right parotids respectively. This demonstrated a good agreement between
      the manual contours and the auto- delineated contours. Our results also showed
      that, without using the tissue appearance model, the auto-delineated parotid
      contours might include nearby bony structures; however, using the appearance
      model was able to correct this problem. CONCLUSIONS: Including the intensity
      information using a tissue appearance model into STAPLE algorithm for multi-atlas
      fusion showed improvement in refining the anatomical boundaries in the multi-
      atlas based auto-segmentation.

PMID- 28519980
TI  - WE-D-213AB-03: Preparing for the ABR Diagnostic Medical Physics Board Exams -
      Oral Exam.
AB  - : Part III (oral exam) is the final part of ABR board exam for Diagnostic Medical
      Physics. In this exam, each of five oral examiners questions the candidate in
      each of five question categories. Oral exam has unique challenges to the
      candidate compared with the written exams. The candidate is expected to have not
      only adequate knowledge on each aspect of imaging physics, but also extensive
      clinical experience on different imaging modalities. The candidate needs to
      demonstrate her/his knowledge and clinical experience by correctly and
      effectively answering specific questions during the exam. Depending on the
      response of the candidate to original question, different follow-up questions are
      usually asked. Therefore, the interaction with examiners plays a critical role in
      the oral exam. The format and question categories of the oral exam in diagnostic
      medical physics will be reviewed. Study materials and effective study methods
      will be discussed. Practical tips on answering questions and interactions with
      examiners during the oral exam will also be shared. LEARNING OBJECTIVES: 1.
      Understand the format and scope of oral exam. 2. Develop an effective method for
      exam preparation. 3. Learn how to effectively answer questions and interact with
      examiners during the exam.

PMID- 28519981
TI  - WE-E-BRB-05: A Novel Detector Dose Calculation Model for in Vivo Delivery
      Verification of IMRT Treatments.
AB  - PURPOSE: Exit 2D detectors are widely used in clinics as a tool for pre-
      treatment field verification. It is desired to have accurate modeling of the
      detector dose for each IMRT plan with patient geometry for in-vivo delivery
      verification. We propose a novel hybrid of model and measurement based methods to
      estimate the detector dose using the information from TPS and plan/verification
      CT. METHODS: Our approach is based on the generalized equivalent field size
      (GEFS) method. It requires two commissioning tables for various square fields
      (l*l, 2*2, ...40*40): the percent depth dose (PDD) table and the detector
      correction factor (DDCF) table. PDDs are retrieved from the treatment planning
      system (TPS), and DDCFs are reconstructed from measurement with various field
      sizes and air gaps (from 5 cm to 50 cm). GEFS models the detector point dose as
      the superposition of annular contribution of the fluence map, which is retrieved
      from the TPS. Correction on the radiological path length is calculated through
      ray-tracing the patient CT. Corrections on the air gap between the couch and
      detector and detector response are applied via table lookup on PDD and DDCF.
      RESULTS: We validated the proposed method using TPS with extended geometry and
      direct clinic measurements for both regular and IMRT fields, various phantom and
      patient geometry. For all calculations, more than 98% of pixels pass the gamma
      index with criteria of 3%, 3mm. Each calculation took only a few seconds on a
      single PC. CONCLUSIONS: We proposed a novel detector dose calculation method that
      can be applied for arbitrary IMRT field and arbitrary patient geometry. The
      calculation is simple and fast and when compared with detector measurement during
      IMRT treatment, makes in- vivo delivery verification and dose reconstruction
      feasible.

PMID- 28519982
TI  - WE-C-217BCD-02: Design of an MR Compatible Rotating Anode X-Ray Tube.
AB  - PURPOSE: To design a rotating anode X-ray tube capable of operating in strong
      magnetic field environments. This tube design can be used in 'close proximity"
      hybrid X-ray/MR system geometries where the imaging fields of view are separated
      by only ~1.2 meters. METHODS: Existing rotating anode X-ray tube designs fail in
      strong magnetic field environments because the fields alter the electron
      trajectories in the tube and act as a brake on the induction motor, reducing the
      rotation speed of the anode. We propose an X- ray tube design that utilizes
      optimized resistive coils to shield a fraction of the MR fringe field. The
      remainder of the correction is performed using bias voltages on electrodes
      adjacent to the x-ray tube filament. Furthermore, we replace the induction motor
      with a novel motor design that is analogous to a three-phase brushed DC motor
      with the MR fringe field serving as the stator field. RESULTS: Space charge
      simulations of the electron optics show that the combined
      magnetostatic/electrostatic method can correct for a magnetic field strength of
      152 mT with approximately 590 A/cm2 applied to the shielding coils and a 35 kV
      potential difference applied to the bias electrodes. A prototype of the motor
      design was machined and assembled. The performance of this prototype motor was
      evaluated at various magnetic field strengths, and was found to accelerate to the
      minimum operating speed of 3000 rpm in 10 seconds for an external field of 60 mT.
      CONCLUSIONS: The space charge simulations validate that the electron trajectories
      can be controlled using our combined approach. Testing of the motor prototype
      demonstrates that our design outperforms existing induction motors in strong
      magnetic field environments. Integrating this design with our modified flat panel
      detector will allow, for the first time, a "close proximity" hybrid system in
      which imaging performance is not compromised. NIH R01 EB007626 Richard M. Lucas
      Foundation Stanford Bio-X Fellowship.

PMID- 28519983
TI  - WE-E-213CD-02: Gaussian Weighted Multi-Atlas Based Segmentation for Head and Neck
      Radiotherapy Planning.
AB  - PURPOSE: To develop a multi-atlas segmentation strategy for IMRT head and neck
      therapy planning. METHODS: The method was tested on thirty-one head and neck
      simulation CTs, without demographic or pathology pre-clustering. We compare Fixed
      Number (FN) and Thresholding (TH) selection (based on normalized mutual
      information ranking) of the atlases to be included for current patient
      segmentation. Next step is a pairwise demons Deformable Registration (DR) onto
      current patient CT. DR was extended to automatically compensate for patient
      different field of view. Propagated labels are combined according to a Gaussian
      Weighted (GW) fusion rule, adapted to poor soft tissues contrast. Agreement with
      manual segmentation was quantified in terms of Dice Similarity Coefficient (DSC).
      Selection methods, number of atlases used, as well as GW, average and majority
      voting fusion were discriminated by means of Friedman Test (a=5%). Experimental
      tuning of the algorithm parameters was performed on five patients, deriving an
      optimal configuration for each structure. RESULTS: DSC reduction was not
      significant when ten or more atlases are selected, whereas DSC for single most
      similar atlas selection is 10% lower in median. DSC of FN selection rule were
      significantly higher for most structures. Tubular structures may benefit from
      computing average contour rather than looking at the singular voxel contribution,
      whereas the best performing strategy for all other structures was GW. When half
      database is selected, final median DSC were 0.86, 0.80, 0.51, 0.81, 0.69 and 0.79
      for mandible, spine, optical nerves, eyes, parotids and brainstem respectively.
      CONCLUSION: We developed an efficient algorithm for multiatlas based segmentation
      of planning CT volumes, based on DR and GW. FN selection of database atlases is
      foreseen to increase computational efficiency. The absence of clinical pre
      clustering and specific imaging protocol on database subjects makes the results
      closer to real clinical application. "Progetto Roberto Rocca" funded by the
      Fondazione Fratelli Agostino and Enrico Rocca, Italy.

PMID- 28519984
TI  - WE-C-217A-01: Risk Estimation versus Risk Perception.
AB  - : The recent attention in the scientific and popular press to the potential risks
      associated with ionizing radiation from medical imaging has resulted in some
      patient becoming unwilling to undergo medically appropriate procedures that use
      ionizing radiation. Scientific data on the magnitude of both potential risks and
      benefits are not always successful in allaying patient concerns, even though the
      potential risks are very small and the potential benefits are very large. An
      understanding of the psychological factors affecting the perception of risk helps
      to explain this behavior. For patients to feel comfortable with medical
      procedures involving ionizing radiation, they must be believe that their medical
      providers have their best interest in mind, that the ordered procedure is
      medically appropriate and may help their doctor in managing their care, and that
      those providing the imaging services are actively engaged in efforts to ensure
      patient safety. LEARNING OBJECTIVES: 1. Differentiate between risk estimation and
      risk perception 2. List several factors that affect a person's perception of risk
      3. Describe some of the consequences that may occur when patients do not feel
      that they are safe.

PMID- 28519985
TI  - WE-E-217A-02: Methodologies for Evaluation of Standalone CAD System Performance.
AB  - Standalone performance evaluation of a CAD system provides information about the
      abnormality detection or classification performance of the computerized system
      alone. Although the performance of the reader with CAD is the final step in CAD
      system assessment, standalone performance evaluation is an important component
      for several reasons: First, standalone evaluation informs the reader about the
      performance level of the CAD system and may have an impact on how the reader uses
      the system. Second, it provides essential information to the system designer for
      algorithm optimization during system development. Third, standalone evaluation
      can provide a detailed description of algorithm performance (e.g., on subgroups
      of the population) because a larger data set with more samples from different
      subgroups can be included in standalone studies compared to reader studies.
      Proper standalone evaluation of a CAD system involves a number of key components,
      some of which are shared with the assessment of reader performance with CAD.
      These include (1) selection of a test data set that allows performance assessment
      with little or no bias and acceptable uncertainty; (2) a reference standard that
      indicates disease status as well as the location and extent of disease; (3) a
      clearly defined method for labeling each CAD mark as a true-positive or false
      positive; and (4) a properly selected set of metrics to summarize the accuracy of
      the computer marks and their corresponding scores. In this lecture, we will
      discuss various approaches for the key components of standalone CAD performance
      evaluation listed above, and present some of the recommendations and opinions
      from the AAPM CAD subcommittee on these issues. Learning Objectives 1. Identify
      basic components and metrics in the assessment of standalone CAD systems 2.
      Understand how each component may affect the assessed performance 3. Learn about
      AAPM CAD subcommittee's opinions and recommendations on factors and metrics
      related to the evaluation of standalone CAD system performance.

PMID- 28519986
TI  - WE-C-217BCD-04: Multimodality Imaging of Breast Cancer Experimental Lung
      Metastasis.
AB  - PURPOSE: Metastatic breast cancer (MBC) is incurable. The clinical gold standard
      for assessing tumor microvessel density (MVD), an independent prognostic marker
      in MBC, is CD 105 staining. The goal of this study is to develop a positron
      emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging of
      CD105 expression in MBC (i.e. non-invasive measurement of MVD), as well as other
      applications such as early detection of metastasis, intraoperative guidance, etc.
      METHODS: TRC105, a chimeric anti-CD105 mAb, was dual-labeled with a NIRF dye and
      89 Zr to yield 8 9 Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast
      cancer cells were injected intravenously into female BALB/c mice to establish a
      lung MBC model. Bio luminescence imaging (BLI) was carried out to non- invasively
      monitor the lung tumor burden. Comprehensive in vivo/ex vivo studies were
      performed to investigate 8 9 Zr-Df-TRC105-800CW in this MBC model. Cetuximab was
      used as an isotype-matched control. RESULTS: Radiolabeled TRC105 has high tumor
      uptake in many tumor types in addition to MBC (e.g. pancreatic/prostate cancer
      and brain tumor), revealing broad clinical potential for TRC105-based agents.
      FACS analysis of HUVECs showed no difference in CD 105 binding between TRC105 and
      Df- TRC105-800CW. PET imaging revealed that 4T1 lung tumor uptake of 89 Zr-Df
      TRC105-800CW was 8.7+/-1.4,10.9+/-0.5, and 9.7+/-1.1 %ID/g at 4, 24, and 48 h
      post-injection (n = 4), with excellent tumor contrast. Bio distribution studies,
      blocking, control studies with 8 9 Zr-Df-cetuximab- 800CW, ex vivo BLI/PET/NIRF
      imaging, and histology all confirmed CD 105 specificity of the tracer. NIRF
      imaging-guided removal of 4T1 tumors with Df-TRC105-800CW in a subcutaneous model
      was also straightforward. CONCLUSIONS: We report the first PET/NIRF imaging of
      CD105 expression in a MBC model. Broad clinical potential of TRC105- based agents
      was shown in many tumor types, which also enabled early detection of small
      metastases and provided intraoperative guidance for tumor removal.

PMID- 28519987
TI  - WE-E-213CD-04: CT to Cone-Beam CT Deformable Registration With Simultaneous
      Intensity Correction.
AB  - PURPOSE: To develop and validate a robust CT to cone-beam (CBCT) deformable image
      registration algorithm that can handle CBCT artifacts and intensity
      inconsistency, and thus can yield accurate registration results. METHODS: We
      propose a new algorithm called Deformation with Intensity Simultaneously
      Corrected (DISC). DISC distinguishes itself from the original demons by
      performing an intensity correction procedure on the CBCT image at every iteration
      step of demons registration. Specifically, the intensity correction of a voxel in
      CBCT is achieved by matching the first and the second moments of the image
      intensities inside a patch around this voxel with those on the CT image. It is
      expected that such a strategy can remove artifacts in the CBCT image, as well as
      ensuring the intensity consistency between the two modalities and hence
      facilitating the registration process. DISC is implemented on computer graphics
      processing units (GPUs) using the compute unified device architecture (CUDA)
      programming environment. The performance of DISC has been qualitatively and
      quantitatively evaluated on a simulated patient case and six head-and- neck
      cancer patient data. RESULTS: Visual inspection shows that original demons
      distorts the tissues after registration, especially in regions which are heavily
      degraded by artifacts. DISC, on the other hand, can effectively register CT and
      CBCT image even in regions contaminated by severe artifacts. The intensity
      corrected CBCT that extracted from the last iteration of DISC is artifact-free
      and has similar histogram distribution with the deformed CT. CONCLUSIONS: We have
      developed a robust CT to CBCT deformable image registration method that properly
      deals with the CBCT artifacts and intensity inconsistency, and thus yields
      accurate registration results. This work is supported in part by the University
      of California Lab Fees Research Program, the Master Research Agreement from
      Varian Medical Systems, Inc., and the grants from the National Natural Science
      Foundation of China (No.30970866).

PMID- 28519988
TI  - WE-C-217A-03: Biology versus Epidemiology: The Need for an Integrated Model of
      Radiation Risk.
AB  - : The lifetime attributable risk estimates from the National Academy of Sciences
      BEIR VII report have been used by a number of authors to estimate cancer
      mortality caused by radiation exposure from medical diagnostic radiology exams.
      This controversial practice assumes that the dose response relationship between
      radiation and cancer is linear with no threshold (LNT). For purposes of
      protecting public health, use of the LNT model is widely accepted. But is it
      appropriate for estimating risk to individuals exposed to low doses of radiation
      from medical procedures? Radiation biology research demonstrates that not all
      biological processes are linear. Italso has provided data that support not only
      LNT but supra linear and sub linear response models. Results from epidemiology
      studies can also be used to support the use of any of these models, but the
      confidence intervals are much larger. Since we can't prove which model is
      correct, for purposes of protecting patients we assume that any exposure has the
      potential for harm and we use optimization to keep exposures as low as reasonably
      achievable.Several areas of research are contributing insight into this dilemma,
      but they still leave several important questions unanswered: * How can we
      accurately extrapolate low-dose biological effects generated in the laboratory to
      risk in a human? * Is extrapolation from high dose, high dose rate, acute
      exposures appropriate when human exposures are primarily chronic low dose
      exposures. Epidemiology alone is unlikely to provide information that will
      resolve this dilemma. The numbers of individuals required in a sample are too
      large, and the homogeneity among subjects is lacking. Reliance on radiation
      biology research alone is problematic because the research is focused primarily
      on mechanisms and not risk. This paper will present an overview of the issues and
      suggest areas of research that may contribute to our understanding of the level
      of risk associated with low doses of medical radiation. LEARNING OBJECTIVES: 1.
      List the current biological mechanisms that are affected by low doses of ionizing
      radiation. 2. Describe the dilemma of risk extrapolation based on current
      knowledge of biological effects of radiation. 3. Discuss the limitations of
      extrapolating lifetime attributable risk estimates to cancer mortality for low
      dose medical procedures.

PMID- 28519989
TI  - WE-E-217A-04: Training and QA Procedures for Using CAD Systems.
AB  - : Computer-aided detection/diagnosis (CAD) devices for radiology are becoming
      increasingly available for clinical use. To achieve the highest possible benefit
      from CAD systems, best practices are required for clinical implementation and use
      of CAD. This lecture will discuss four areas of interest to the medical physics
      community pertaining to CAD best practices: off-label use and pitfalls, user
      training, QA of CAD use, and academic opportunities for quality assurance (QA)
      research. FINANCIAL DISCLOSURE: Patent royalties from and research agreement with
      iCAD; software license to Translational Sciences Corporation. LEARNING
      OBJECTIVES: 1. Understand benefits of PACS integration of CAD. 2. Identify
      potential issues with off-label use of CAD. 3. Understand the importance of user
      training relating to CAD devices. 4. Learn potential QA procedures to assure
      proper use of CAD as designed. 5. Learn about areas of CAD user training and QA
      that could benefit from further research.

PMID- 28519990
TI  - WE-E-BRCD-01: SBRT Treatment Planning: Practical Considerations.
AB  - : Stereotactic Body Radiation Therapy (SBRT) is being increasingly used in the
      radiation oncology community to treat tumors in extra-cranial sites such as
      spine, lung, liver, pancreas and prostate. There are well established RTOG
      protocols (e.g. RTOG 0631 for spine, RTOG 0813 and 0915 for lung and RTOG 0438
      for liver) that specify detailed requirements for treatment planning of SBRT
      plans. SBRT plans have to meet strict criteria on maximum PTV dose, prescription
      isodose, prescription isodose surface coverage, high dose spillage and
      intermediate dose spillage in addition of the constraints of dose limiting organs
      at risk. This lecture aims to educate members on treatment planning issues for
      SBRT cases with concentration on strategies to create highly inhomogeneous dose
      distributions inside the PTV and steep dose gradients in the surrounding normal
      tissues. LEARNING OBJECTIVES: 1. What characteristics SBRT plans have and how
      they are different from conventional fractionated radiotherapy plans. 2. For
      IMRT/VMAT SBRT plans (such as spine SBRT plans that concave distributions around
      the cord are required), we will discuss strategies that can be employed to
      overcome many commercial treatment planning system's IMRT algorithms' intrinsic
      penalty for inhomogeneous plans. Additional issues related to VMAT will be also
      discussed. 3. For non-IMRT SBRT plans (such as many lung or liver cases where
      target motion is a concern), we will discuss techniques to control dose
      inhomogeneities and dose fall off. 4. We will also discuss policy and procedures
      on SBRT patient setup and verification issues to ensure safe delivery of SBRT
      treatments.

PMID- 28519991
TI  - WE-E-BRB-11: Riview a Web-Based Viewer for Radiotherapy.
AB  - PURPOSE: Collaborations involving radiotherapy data collection, such as the
      recently proposed international radiogenomics consortium, require robust, web
      based tools to facilitate reviewing treatment planning information. We present
      the architecture and prototype characteristics for a web-based radiotherapy
      viewer. METHODS: The web-based environment developed in this work consists of the
      following components: 1) Import of DICOM/RTOG data: CERR was leveraged to import
      DICOM/RTOG data and to convert to database friendly RT objects. 2) Extraction and
      Storage of RT objects: The scan and dose distributions were stored as .png files
      per slice and view plane. The file locations were written to the MySQL database.
      Structure contours and DVH curves were written to the database as numeric data.
      3) Web interfaces to query, retrieve and visualize the RT objects: The Web
      application was developed using HTML 5 and Ruby on Rails (RoR) technology
      following the MVC philosophy. The open source ImageMagick library was utilized to
      overlay scan, dose and structures. The application allows users to (i) QA the
      treatment plans associated with a study, (ii) Query and Retrieve patients
      matching anonymized ID and study, (iii) Review up to 4 plans simultaneously in 4
      window panes (iv) Plot DVH curves for the selected structures and dose
      distributions. RESULTS: A subset of data for lung cancer patients was used to
      prototype the system. Five user accounts were created to have access to this
      study. The scans, doses, structures and DVHs for 10 patients were made available
      via the web application. CONCLUSIONS: A web-based system to facilitate QA, and
      support Query, Retrieve and the Visualization of RT data was prototyped. The
      RIVIEW system was developed using open source and free technology like MySQL and
      RoR. We plan to extend the RIVIEW system further to be useful in clinical trial
      data collection, outcomes research, cohort plan review and evaluation.

PMID- 28519992
TI  - WE-C-217BCD-08: Rapid Monte Carlo Simulations of DQE(f) of Scintillator-Based
      Detectors.
AB  - PURPOSE: Monte Carlo simulations of DQE(f) can greatly aid in the design of
      scintillator-based detectors by helping optimize key parameters including
      scintillator material and thickness, pixel size, surface finish, and septa
      reflectivity. However, the additional optical transport significantly increases
      simulation times, necessitating a large number of parallel processors to
      adequately explore the parameter space. To address this limitation, we have
      optimized the DQE(f) algorithm, reducing simulation times per design iteration to
      10 minutes on a single CPU. METHODS: DQE(f) is proportional to the ratio, MTF(f)2
      /NPS(f). The LSF-MTF simulation uses a slanted line source and is rapidly
      performed with relatively few gammas launched. However, the conventional NPS
      simulation for standard radiation exposure levels requires the acquisition of
      multiple flood fields (nRun), each requiring billions of input gamma photons
      (nGamma), many of which will scintillate, thereby producing thousands of optical
      photons (nOpt) per deposited MeV. The resulting execution time is proportional to
      the product nRun x nGamma x nOpt. In this investigation, we revisit the
      theoretical derivation of DQE(f), and reveal significant computation time savings
      through the optimization of nRun, nGamma, and nOpt. Using GEANT4, we determine
      optimal values for these three variables for a GOS scintillator-amorphous silicon
      portal imager. Both isotropic and Mie optical scattering processes were modeled.
      Simulation results were validated against the literature. RESULTS: We found that,
      depending on the radiative and optical attenuation properties of the
      scintillator, the NPS can be accurately computed using values for nGamma below
      1000, and values for nOpt below 500/MeV. nRun should remain above 200. Using
      these parameters, typical computation times for a complete NPS ranged from 2-10
      minutes on a single CPU. CONCLUSIONS: The number of launched particles and
      corresponding execution times for a DQE simulation can be dramatically reduced
      allowing for accurate computation with modest computer hardware. NIHRO1 CA138426.
      Several authors work for Varian Medical Systems.

PMID- 28519993
TI  - WE-E-213CD-08: A Novel Level Set Active Contour Algorithm Using the Jensen-Renyi
      Divergence for Tumor Segmentation in PET.
AB  - PURPOSE: Positron emission tomography (PET) presents a valuable resource for
      delineating the biological tumor volume (BTV) for image-guided radiotherapy.
      However, accurate and consistent image segmentation is a significant challenge
      within the context of PET, owing to its low spatial resolution and high levels of
      noise. Active contour methods based on the level set methods can be sensitive to
      noise and susceptible to failing in low contrast regions. Therefore, this work
      evaluates a novel active contour algorithm applied to the task of PET tumor
      segmentation. METHODS: A novel active contour segmentation algorithm based on
      maximizing the Jensen-Renyi Divergence between regions of interest was applied to
      the task of segmenting lesions in 7 patients with T3-T4 pharyngolaryngeal
      squamous cell carcinoma. The algorithm was implemented on an NVidia GEFORCE GTV
      560M GPU. The cases were taken from the Louvain database, which includes contours
      of the macroscopically defined BTV drawn using histology of resected tissue. The
      images were pre-processed using denoising/deconvolution. RESULTS: The segmented
      volumes agreed well with the macroscopic contours, with an average concordance
      index and classification error of 0.6 +/- 0.09 and 55 +/- 16.5%, respectively.
      The algorithm in its present implementation requires approximately 0.5-1.3 sec
      per iteration and can reach convergence within 10-30 iterations. CONCLUSIONS: The
      Jensen-Renyi active contour method was shown to come close to and in terms of
      concordance, outperforms a variety of PET segmentation methods that have been
      previously evaluated using the same data. Further evaluation on a larger dataset
      along with performance optimization is necessary before clinical deployment.

PMID- 28519994
TI  - WE-D-213AB-02: Preparing the ABR Diagnostic Exam: Part II.
AB  - : Preparing for Part II of the Diagnostic Medical Physics American Board of
      Radiology exam requires a different approach than studying for Part I of the
      exam. As Part II is the first exam that splits apart the different medical
      physics disciplines, it is unsurprising that the best preparation for the exam is
      clinical experience. A well-rounded clinical physics training program and a
      review of texts covering the fundamentals of the various imaging modalities
      should leave examinees confident in their ability to successfully complete Part
      II. Completion of a CAMPEP accredited residency program is excellent preparation
      for Part II, and individuals sitting for the exam who have not completed a
      residency would do well to gain as much clinical experience in the different
      imaging modalities as possible. This presentation will focus on important
      clinical experiences and topics to focus on and useful resources to review
      diagnostic medical physics fundamentals in advance of taking Part II. LEARNING
      OBJECTIVES: 1. Become familiar with useful refresher material for Part II 2.
      Understand the importance of a broad and deep history of clinical experience 3.
      Be able to identify relevant topics that may be included on the exam.

PMID- 28519995
TI  - WE-E-BRB-04: Quantitative Dose Tracking Enabled Through a Novel Deformable 3D
      Dosimeter.
AB  - PURPOSE: To evaluate and investigate the feasibility of a new method for
      validating dose tracking algorithms in deforming tissues using a novel deformable
      3D dosimeter. METHODS: A novel deformable 3D Presage dosimeter is reported
      consisting of a stretchy polyurethane matrix doped with radiochromic leuco-dye.
      Two deformable cylindrical dosimeters (6 cm diameter, 5 cm long) were
      manufactured and irradiated with a checkerboard arrangement of 5 mm square pencil
      beams created by MLC fields. One dosimeter was irradiated under lateral
      compression by 33% (6 cm down to 4 cm diameter) to simulate a deformed organ. A
      second control dosimeter was irradiated with the same checkerboard pattern but
      without deformation applied. High-resolution 3D dose distributions (isotropic 1
      mm resolution) were obtained by optical-CT imaging. Physical dose deformation was
      quantified by comparing checkerboard pencil beam shapes and positions in the
      deformed and control dosimeters. RESULTS: Deformation of dose in the deformed
      dosimeter was clearly visible in all 3 dimensions. The deformed checkerboard dose
      pattern showed expansion of 16% - 46% along the axis of compression, with higher
      expansion observed in the central regions of the dosimeter. Perpendicular to the
      compression axis, the dose pattern contracted by 7% - 13%. Peak dose changes of 
      6% and +30% were observed parallel and perpendicular to the compression axis
      respectively. Dose response was linear from 0-8 Gy. CONCLUSIONS: Dose tracking
      was successfully quantified in a novel deforming 3D dosimeter. This capability
      has potential as a powerful new method for validating deformable dose tracking
      and registration algorithms. NCI R01CA100835.

PMID- 28519996
TI  - WE-C-217BCD-01: Development of an Integrated Multimodal Imaging System (IMIS) for
      Surgical Guidance.
AB  - PURPOSE: To develop an intraoperative multimodal imaging system (IMIS) for
      surgical guidance, combining gamma ray scintigraphy with a video camera system
      for simultaneous real-time visible and near infrared fluorescence (NIRf) imaging.
      METHODS: The gamma camera component has been tested in a pilot human study for
      intraoperative SLN biopsy in melanoma patients. To characterize the optical
      components, the spatial resolution of the visible light video camera, the depth
      dependent visualization by the NIRf system of targets containing indocyanine
      green (ICG) and the excitation radiation rejection of the NIRf system were
      evaluated in bench-top tests. Spatial resolution was quantified using a USAF test
      pattern and NIRf performance was evaluated using phantoms containing fluorescent
      targets in mixtures of fat-emulsion (Intralipid) and india ink to simulate
      optical transport in human tissue. The visible/NIRf system was also used to image
      a live anaesthetized mouse model of breast cancer. RESULTS: Intraoperatively the
      SiPM gamma camera detected 100% of positive lymph nodes. The visible light camera
      system contrast transfer function is >10% up to 3.2 1p/mm. The NIRf image SNR
      when imaging a 9.9 mm diameter lesion containing a 20 MUM ICG concentration is >
      2 for lesion depths up to 8 mm. The current combination of excitation and
      emission filters results in nearly complete rejection of backscattered light,
      resulting in a leakage count rate less than 1% of the system dark count rate.
      CONCLUSIONS: The optical component of the IMIS system demonstrates high spatial
      resolution, excellent rejection of background excitation radiation, and good
      target SNR for realistic tracer concentration and target depth. It is capable of
      accurately coregistered video rate visible/NIRf imaging.

PMID- 28519997
TI  - WE-E-213CD-01: Best in Physics (Joint Imaging-Therapy) - Evaluation of
      Deformation Algorithm Accuracy with a Two-Dimensional Anatomical Pelvic Phantom.
AB  - PURPOSE: To objectively evaluate the accuracy of 11 different deformable
      registration techniques for bladder filling. METHODS: The phantom represents an
      axial plane of the pelvic anatomy. Urethane plastic serves as the bony anatomy
      and urethane rubber with three levels of Hounsfield units (HU) is used to
      represent fat and organs, including the prostate. A plastic insert is placed into
      the phantom to simulate bladder filling. Nonradiopaque markers reside on the
      phantom surface. Optical camera images of these markers are used to measure the
      positions and determine the deformation from the bladder insert. Eleven different
      deformable registration techniques are applied to the full- and empty-bladder
      computed tomography images of the phantom to calculate the deformation. The
      applied algorithms include those from MIMVista Software and Velocity Medical
      Solutions and 9 different implementations from the Deformable Image Registration
      and Adaptive Radiotherapy Toolbox for Matlab. The distance to agreement between
      the measured and calculated deformations is used to evaluate algorithm error.
      Deformable registration warps one image to make it similar to another. The root
      mean-square (RMS) difference between the HUs at the marker locations on the empty
      bladder phantom and those at the calculated marker locations on the full-bladder
      phantom is used as a metric for image similarity. RESULTS: The percentage of the
      markers with an error larger than 3 mm ranges from 3.1% to 28.2% with the
      different registration techniques. This range is 1.1% to 3.7% for a 7 mm error.
      The least accurate algorithm at 3 mm is also the most accurate at 7 mm. Also, the
      least accurate algorithm at 7 mm produces the lowest RMS difference. CONCLUSIONS:
      Different deformation algorithms generate very different results and the outcome
      of any one algorithm can be misleading. Thus, these algorithms require quality
      assurance. The two-dimensional phantom is an objective tool for this purpose.

PMID- 28519998
TI  - WE-C-217BCD-12: Irreversible Two-Tissue Compartment Model Fitting for Dynamic 18F
      FDG PET: A Practical Comparison of Methods Using Simulated Time- Activity Data.
AB  - PURPOSE: To compare techniques of fitting simulated Dynamic 18F-FDG PET time
      activity curves to the irreversible two-tissue compartment model. The precision
      and accuracy of various algorithms were assessed in the presence of measurement
      error and with a practical focus on CPU time. METHODS: Dynamic PET analysis is
      often applied to multiple individual voxels, leading to concerns regarding time
      efficiency, yet a reluctance to compromise on accuracy. This study evaluates
      selected fitting algorithms in terms of the precision/bias of fitted parameters
      and run-time. As a standard for comparison, biological parameters were fixed at
      typical values (K1=0.2, k2=0.25, k3=0.05, K&#7522;=0.3334). Tissue time-activity
      curves were generated using the model equation and by incorporating activity/time
      dependent Gaussian noise. The following algorithms were then applied: Genetic,
      Conjugate Gradient (CG), Gradient Descent (GD), Simulated Annealing (SA),
      Levenberg-Marquardt (LMQ), Gauss-Newton (GN), and Limited-BFGS (L-BFGS). Non
      iterative, problem specific approaches were also considered: Patlak analysis (K?
      only), and Blomqvist linearization (BL). Parameter accuracy and precision were
      quantified with relative errors (REs). RESULTS: At typical noise levels, maximal
      REs were >60% (resulting in |I'K?|>10%) for GD and SA, <20% for BL (|I'K?|<6%)
      and Patlak (|I'K?|<4%), and <15% (|I'K?|<2%) with other methods. On average, the
      highest fidelity parameter estimates (rate-constant REs<2.5%, |I'K?|<0.15%) were
      attained with L-BFGS, GN, and LMQ. In contrast, the non-iterative methods
      provided poorer estimates (RE between 1-7%), though run-time (<0.05 ms) was 100
      1000x less. Using BL results as initial estimates for L- BFGS (BL+L-BFGS), GN
      (BL+GN) or LMQ (BL+LMQ) yielded rapid convergence (<0.1 ms), while maintaining
      superiority with respect to parameter bias. CONCLUSIONS: Poor choice of a fitting
      algorithm may lead to significant errors in estimated kinetic parameters and/or
      unpractically high computation times. Thus, our recommendation is the use of BL+L
      BFGS, BL+GN or BL+LMQ, which is contrary to the gold standards, Patlak and LMQ
      (alone), commonly seen in the literature.

PMID- 28519999
TI  - WE-E-217A-01: CAD: Quality Assurance of CAD Systems Implemented in Clinical Use.
AB  - PURPOSE: We propose a new metric called Distance Discordance (DD), which is
      defined as the distance between two anatomic points from two moving images, which
      are co-located on some reference image, when deformed onto another reference
      image. METHODS: To demonstrate the concept of DD, we created a reference software
      phantom which contains two objects. The first object (1) consists of a hollow box
      with a fixed size core and variable wall thickness. The second object (2)
      consists of a solid box of fixed size and arbitrary location. 7 different
      variations of the fixed phantom were created. Each phantom was deformed onto
      every other phantom using two B-Spline DIR algorithms available in Elastix and
      Plastimatch. Voxels were sampled from the reference phantom [1], which were also
      deformed from moving phantoms [2...6], and we find the differences in their
      corresponding location on phantom [7]. Each voxel results in a distribution of DD
      values, which we call distance discordance histogram (DDH). We also demonstrate
      this concept in 8 Head & Neck patients. RESULTS: The two image registration
      algorithms produced two different DD results for the same phantom image set. The
      mean values of the DDH were slightly lower for Elastix (0-1.28 cm) as compared to
      the values produced by Plastimatch (0-1.43 cm). The combined DDH for the H&N
      patients followed a lognormal distribution with a mean of 0.45 cm and std.
      deviation of 0.42 cm. CONCLUSIONS: The proposed distance discordance (DD) metric
      is an easily interpretable, quantitative tool that can be used to evaluate the
      effect of inter-patient variability on the goodness of the registration in
      different parts of the patient anatomy. Therefore, it can be utilized to exclude
      certain images based on their DDH characteristics. In addition, this metric does
      not rely on 'ground truth' or the presence of contoured structures.

PMID- 28520000
TI  - WE-E-217BCD-02: Update on the Upcoming ACR Digital Mammography QC Manual.
AB  - PURPOSE: We propose a new metric called Distance Discordance (DD), which is
      defined as the distance between two anatomic points from two moving images, which
      are co-located on some reference image, when deformed onto another reference
      image. METHODS: To demonstrate the concept of DD, we created a reference software
      phantom which contains two objects. The first object (1) consists of a hollow box
      with a fixed size core and variable wall thickness. The second object (2)
      consists of a solid box of fixed size and arbitrary location. 7 different
      variations of the fixed phantom were created. Each phantom was deformed onto
      every other phantom using two B-Spline DIR algorithms available in Elastix and
      Plastimatch. Voxels were sampled from the reference phantom [1], which were also
      deformed from moving phantoms [2...6], and we find the differences in their
      corresponding location on phantom [7]. Each voxel results in a distribution of DD
      values, which we call distance discordance histogram (DDH). We also demonstrate
      this concept in 8 Head & Neck patients. RESULTS: The two image registration
      algorithms produced two different DD results for the same phantom image set. The
      mean values of the DDH were slightly lower for Elastix (0-1.28 cm) as compared to
      the values produced by Plastimatch (0-1.43 cm). The combined DDH for the H&N
      patients followed a lognormal distribution with a mean of 0.45 cm and std.
      deviation of 0.42 cm. CONCLUSIONS: The proposed distance discordance (DD) metric
      is an easily interpretable, quantitative tool that can be used to evaluate the
      effect of inter-patient variability on the goodness of the registration in
      different parts of the patient anatomy. Therefore, it can be utilized to exclude
      certain images based on their DDH characteristics. In addition, this metric does
      not rely on 'ground truth' or the presence of contoured structures.

PMID- 28520001
TI  - WE-C-217A-02: BEIR VII: What It Does and Doesn't Say.
AB  - : Over the last 2 years, there has been considerable attention focused on the
      potential cancer risks from medical imaging procedures, particularly with the
      widespread use of multislice CT. Almost all studies rely upon the BEIR VII report
      (Biological Effects of Ionizing Radiation panel formed under the auspices of the
      National Academy of Sciences) to generate an estimate of the risk of cancer from
      a given procedure. In doing so, most studies treat the BEIR VII report as a solid
      basis of scientific evidence for estimation of cancer risk. In reality, a close
      reading of this report shows that there are a large number of assumptions
      inherent in all aspects of the estimates of cancer risk - a fact that is often
      and clearly stated in the report. This presentation will review some of the
      assumptions used by the BEIR panel to calculate cancer risk, including the impact
      of different models (excess absolute risk vs. excess relative risk), the dose and
      dose rate effectiveness factor (DDREF) and relative biological effectiveness
      (RBE), on cancer estimates. Often lost in the discussion on medical exposure is a
      reference level by which exposure levels can be compared to something that
      unavoidable and impacts everyone on earth - background radiation. This
      presentation will review the consequences of applying the BEIR model to
      background radiation and known variations in levels of background radiation
      throughout the U.S., and how the cancer rate from background compares with that
      from medical imaging. LEARNING OBJECTIVES: 1. Understand the assumptions
      underlying the BEIR VII report 2. Be able to compare the relative risks of
      medical imaging procedures to that from background radiation.

PMID- 28520002
TI  - WE-E-217A-03: Methodologies for Evaluation of Effects of CAD on Users.
AB  - CAD devices are specifically designed to aid the user in the diagnostic process.
      Therefore, the user (e.g., clinician) is an integral part of the CAD
      interpretation process and the impact of CAD on users needs to be accounted for
      in the assessment process. We use the term "reader performance assessment" to
      denote a test specifically designed to estimate the performance of the user (or
      reader) interpreting CAD as part of the diagnostic process. These reader
      assessment studies are generally more indicative of clinical performance compared
      with standalone testing. In this course, we will update the audience on the
      latest approaches and metrics being used to assess the impact of CAD on user
      performance, and discuss the opinions of the AAPM CAD subcommittee on the
      evaluation methodologies, Learning Objectives: 1. To review the most common
      reader performance assessment techniques and associated performance metrics
      including the multireader multi-case (MRMC) study design. 2. To review the AAPM
      CAD subcommittee's current thinking on best practices for performing and
      analyzing CAD reader performance assessment studies. 3. To understand the
      importance and limitations of various reader performance assessment approaches
      and metrics for various classes of CAD devices.

PMID- 28520004
TI  - WE-E-BRB-10: DosCheck - an Electronic Chart Checking Tool for Dosimetrists.
AB  - PURPOSE: In addition to treatment planning, dosimetrists have to prepare
      documentation and manually enter data in treatment management system (TMS) which
      did not transfer or setup automatically. The required documents and data are
      dependent on the disease site, treatment machine and clinical workflow. Errors
      and inconsistencies can cause redundant work, treatment delays and potentially
      treatment errors. To address these issues, an electronic checking software tool,
      DosCheck was clinically implemented to check the existence of necessary
      documentations and the integrity of manually-entered data. The purpose of this
      software is to reduce the frequency of human errors and to improve efficiency.
      METHODS: DosCheck reads data and documents from 1) TMS, 2) Pinnacle TPS, and 3)
      DICOM plan files stored in a DICOM-RT PACS. It processes documents in Word and
      PDF format, treatment plan data in Pinnacle native format and DICOM format, and
      Mosaiq data in database records. The software cross-checks data accuracy and
      consistency by following rules that are pre-defined according to the clinical
      requirements and treatment sties. It interacts with dosimetrists and presents
      instantaneous results via graphical user interface. RESULTS: DosCheck has been
      implemented in C#. It performs a full check for a patient with 20 seconds. It has
      been clinically commissioned and is used daily by all dosimetrists at our
      institution. Retrospective analysis shows that DosCheck identifies 30% to 40% of
      previously reported dosimetrist human errors. Additional ~30% errors are checked
      by other tools that could be integrated DosCheck in the near future. CONCLUSIONS:
      As an electronic data checking tool, DosCheck can obtain and process data and
      documents from multiple clinical computer systems in the radiation oncology
      department, and perform checks according to clinical rules. It is able to improve
      the accuracy and efficiency of clinical data and document process, and therefore
      to reduce any potential inconsistencies and errors.

PMID- 28520005
TI  - WE-C-217BCD-07: Best in Physics (Joint Eyiaging-Therapy) - Direct Imaging of the
      Uptake of Platinum Anticancer Agents Using X-Ray Stimulated Fluorescence: A Proof
      Of-Concept Study.
AB  - PURPOSE: Platinum-based (Pt) chemotherapy has greatly improved the initial
      response rate of different cancers. However, relapse of a drug-resistant tumor
      occurs with a high frequency, resulting in poor long term survival. The most
      common phenotype of Pt chemoresistance is decreased Pt drug accumulation in the
      tumor region due to either decreased influx or increased efflux, which is
      invisible for current imaging modalities. The inability of imaging methods to
      directly image the Pt drug uptake has resulted in a very unfavorable scenario for
      early assessment of chemotherapeutic efficacy as well as for personalized
      treatment planning. In this study, we investigated the feasibility of imaging the
      uptake and retention of Pt drugs using x-ray stimulated fluorescence CT (XSF-CT).
      METHODS: Pt is a high atomic number element, and it emits XSF photons when
      excited by ionizing photons. Therefore, the alteration of spatial distribution
      and concentration of Pt drugs in the cancer region could be monitored with XSF
      CT. In this study, a polychromatic X-ray source was used to stimulate emission of
      XSF photons from the Pt drugs. XSF-CT used a first-generation CT geometry. The
      data were collected using a cadmium telluride detector to sort out a set of
      spectra. The spectra were then used to generate sinogram. The bio distribution
      and concentration of each element were reconstructed with the ML-EM algorithm.
      RESULTS: The reconstructed images clearly identified the distributions of
      cisplatin. A good linearity between XSF intensities and the concentrations of
      cisplatin was also observed, suggesting that XSF-CT is capable of quantitative
      imaging. The X-ray dose for stimulating the XSF photon was 0.25 cGy per
      projection. CONCLUSIONS: XSF-CT has the potential to be a promising modality for
      monitoring the intervention processes within X-ray scanners. It would afford a
      powerful way to reliably modify an ineffective treatment regimen in nearly real
      time. This work was supported by NIH/NCI grants (CA133474, CA153587), an NSF
      grant (0854492) and a grant from the Friends for an Earlier Breast Cancer Test
      Foundation.

PMID- 28520008
TI  - WE-F-BRCD-01: Transitioning from 3D IMRT to 4D IMRT and Role of Image Guidance.
AB  - Tumors often change shape and position over the course of Radiation Therapy. The
      adaptation of the treatment to these changes, or its initial design to be robust
      in light of these changes, can be referred to as 4D radiation therapy. The 4th
      dimension is time and includes short term (intrafraction) and longer term (inter
      fraction) changes. IMRT is an important modality for designing plans that can be
      optimized for or can adapt to these changes. The combination of management of the
      tumor changes and the optimization of the radiotherapy plans to deal with these
      changes is 4DIMRT and will be the focus of this 2 part talk. Part 1 : Head and
      Neck and Prostate treatments, focusing on adaptive therapy and image guidance.
      Part 2: Thoracic treatments focusing on 4DCT, IGRT, IMRT in the lung and motion
      management strategies Learning Objectives: 1. Understand currently available IGRT
      and 4DCT technologies 2. Explain how these technologies can be used to improve
      dose delivery precision and accuracy, in particular with dynamically changing
      tumor volumes 3. Understand the challenges and strategies in clinical
      implementation of IMRT in head and neck, prostate, and thorax.

PMID- 28520006
TI  - WE-E-213CD-07: Deformable Registration Between CT and Truncated CBCT for Adaptive
      Therapy Dose Calculation.
AB  - PURPOSE: Deformable image registration (DIR) is a crucial step in adaptive
      radiation therapy (ART) to deform the planning CT to the current CBCT for dose
      calculation and for contour propagation. CBCT images are sometimes truncated in
      the axial plane due to limited field of view (FOV). DIR between CT and truncated
      CBCT often leads to unphysical results, especially in and near missing regions,
      which may result in significant errors in dose calculation afterwards. The
      purpose of this work is to develop and evaluate a method to improve existing DIR
      algorithms to solve the truncation problem. METHODS: The radius of FOV of CBCT is
      first estimated. A recently developed robust CT-CBCT DIR algorithm, called
      Deformation with Intensity Simultaneously Corrected (DISC), is used for
      deformation field calculation. At each iteration of DISC, the calculated
      deformation vector field outside the FOV is replaced by a smooth propagation of
      the deformation field inside the FOV. Six head-and-neck cancer cases and two
      prostate cancer cases are used for evaluation. Dose calculation is performed to
      test the impacts on the resulting dose distribution. RESULTS: In terms of DIR
      accuracy, it is found that the average normalized mutual information (NMI),
      normalized cross correlation (NCC) and feature similarity index (FSIM) increase
      from 0.638, 0.948 and 0.917, to 0.641, 0.951 and 0.919, respectively, when
      compared with DISC without propagation. In terms of dose distribution, the
      relative L2 distance of dose (inside the FOV) between the ground truth and that
      calculated on deformed CT with propagation reduces from 9.25%to 1.41%, compared
      with those without propagation. CONCLUSIONS: We have developed a deformation
      field propagation method for DIR to register the planning CT and the CBCT image
      with small FOV. Tests on head-and-neck and prostate cancer cases have
      demonstrated that our algorithm can generate more accurate registration results
      for dose calculation. This work is supported in part by the University of
      California Lab Fees Research Program, the Master Research Agreement from Varian
      Medical Systems, Inc., and the grants from the National Natural Science
      Foundation of China (No.30970866).

PMID- 28520009
TI  - WE-E-BRB-03: Development of a Deformable Dosimetric Phantom for Verification of
      4D Dose Calculation Algorithms.
AB  - PURPOSE: To develop a deformable lung phantom to verify voxel mapping and dose
      accumulation in 4D dose calculation algorithms used under different scenarios of
      tissue compression. METHODS: The phantom consists primarily of a heterogeneous
      sponge with an embedded tissue-equivalent tumor. The sponge is wrapped in a latex
      balloon housed in a Lucite cylinder. The balloon is attached to a piston that
      compresses the sponge to mimic the human diaphragm. The phantom was programmed to
      simulate different breathing patterns. Radiochromic films and TLD were embedded
      in the sponge for 4D dosimetry algorithm verification. 37 anatomical landmarks
      were manually tracked to verify voxel mappings for four deformable image
      registration (DIR) algorithms: in-house developed Demons and finite element model
      algorithms, and two B-Spline based Velocity AI registration algorithms performed
      between end-inhale and end-exhale. A 6MV photon beam was simulated with
      BEAMnrc/DOSXYZnrc on the end-inhale image with the dose mapped to the end-exhale
      using voxel-based linear dose mapping (LDM) and particle-based energy-mass
      congruence mapping (EMCM) methods. RESULTS: The mean density of the artificial
      lung was increased by 10.2% as the sponge was compressed by 2.5cm. The
      reproducibility of the phantom deformation was within image resolution (1*1*3
      mm3), and the accuracy of four DIR registrations of the extreme phases was within
      3.0mm. With the same registration displacement vector field (DVF), EMCM and LDM
      had different doses mapped to the end- exhale image. Their difference at the
      center of a beam was up to 8.3% for a Demons DVF and 5.8% for a Velocity DVF. The
      maximum difference between EMCM and LDM was 13.2% at beam penumbra. CONCLUSIONS:
      The developed deformable dosimetric phantom readily demonstrated variations among
      different dose addition and image registration algorithms, and is appropriate to
      serve as a QA tool for verification of 4D dose calculation algorithms. The
      research was supported by NIH/NCI R01CA140341.

PMID- 28520010
TI  - WE-E-BRA-03: MR Functional Imaging to Guide Radiotherapy: Opportunities and
      Challenges in the Clinic.
AB  - : Human tumors are characterized by an abnormal vascular network that develops
      because of unregulated angiogenesis. This contributes to abnormalities of the
      tumor microenvironment like hypoxia, acidosis and high interstitial fluid
      pressure that influence treatment response and patient survival. There is an
      important clinical need to develop new minimally invasive tools for
      characterizing the tumor microenvironment at diagnosis, and monitoring changes
      during treatment with radiotherapy, chemotherapy or new biologically targeted
      drugs. MR-based imaging approaches offer exciting possibilities that have yet to
      be fully exploited. Dynamic contrast enhanced (DCE) MR allows the functional
      characteristics of the tumor vasculature to be interrogated serially over time.
      Studies in human cancers have shown substantial differences in DCE MR parameters
      between tumor and normal muscle in keeping with higher blood flow and vascular
      permeability. DCE MR has been shown to correlate with response to radiotherapy or
      drugs that specifically target the tumor vasculature. However, despite important
      advances, MR functional imaging has not been adopted in routine clinical
      practice, in part because of a lack of consensus on optimal imaging techniques,
      analysis methods and reporting metrics. Further refinement and standardization is
      required founded on interdisciplinary collaboration among clinicians, medical
      imagers, biologists, physicists and mathematicians to make these techniques
      robust and clinically applicable. LEARNING OBJECTIVES: 1. Discuss the clinical
      use of MR functional imaging in patients receiving radiotherapy and the
      challenges to wide-spread clinical utilization. 2. Discuss the value of MR
      functional imaging as a predictor of clinical outcome in patients receiving
      radiotherapy, and a means of monitoring biologic response over a course of
      fractionated treatment. 3. Understand the role of MR functional imaging in the
      evaluation of new treatment strategies comprised of radiotherapy and drugs that
      specifically target the tumor vasculature.

PMID- 28520003
TI  - WE-E-213AB-01: Medical Physics Challenges for Implementation of New Technologies
      in External Beam Radiotherapy.
AB  - : The AAPM has signed two formal Educational Exchange Agreements with the Spanish
      (SEFM) and the Russian (AMPR) medical physics societies. While the primary
      purpose of the Agreements is to provide educational opportunities for young
      medical physicists, the Agreements also contemplate holding joint sessions at
      scientific congresses. The purpose of this professional AAPM/SEFM/AMPR Joint
      Symposium is to explore the challenges that medical physicists in the three
      countries face when new external beam radiotherapy technologies are introduced in
      their facilities and to suggest potential solutions to limitations in testing
      equipment and lack of familiarity with protocols. Speakers from the three
      societies will present reviews of the technical aspects of IMRT, Arc EVIRT
      (IMAT/VMAT/Rapid Arc), SRS/SRBT, and IGRT/Adaptive radiotherapy, and will
      describe the status of these technologies in their countries, including the
      challenges found in tasks such as developing anatomical and biological dose
      optimization techniques and implementing QA management, risk assessment and
      patient safety programs. The SEFM will offer AAPM and AMPR members the
      possibility to participate in collaborative proposals for future research bids in
      UE and USA based on an ongoing Spanish project for adaptive radiotherapy using
      functional imaging. A targeted discussion will debate three propositions: the
      cost/benefit ratio of IGRT, whether IMRT requires IGRT, and the use of non
      ionizing radiation technologies for realtime monitoring of prostate IGRT. For
      these debates, each society has designated one speaker to present and defend
      either "For" or "Against" the proposition, followed by discussion by all
      participants. The Symposium presentations and the country-tailored
      recommendations drawn will be made available to each society for inclusion in
      their websites. The WGNIMP, the AAPM Work Group charged with executing the
      AAPM/SEFM and AAPM/AMPR Agreements, will follow up on the commitments made by the
      AAPM.Di Yan's research on adaptive radiotherapy has been financially supported
      by: 1) NIH Research Grants, 2) Elekta Research Grants 3) Philips Research
      GrantConflicts of interest for Cedric X Yu: 1) Board Member of Prowess, Inc., 2)
      Shareholder of Xcision Medical Systems, LLC, 3) Inventor on patents licensed by
      Varian Medical Systems, Inc. LEARNING OBJECTIVES: 1. Describe fundamental aspects
      for four advanced radiotherapy techniques: IMRT, IGRT, SBRT, and adaptive
      radiotherapy. 2. Review technical and professional challenges for implementation
      of advanced techniques as a function of resources and capabilities available
      within each scientific society: AAPM, SEFM, and AMPR. 3. Discuss and plan a
      proposal for an international trial on IMRT/IGRT based on functional imaging. 4.
      Debate important implementation aspects of IMRT and IGRT according to country
      specific resources.

PMID- 28520011
TI  - WE-C-217BCD-11: Coupled Radiative and Optical Geant4 Simulation of MV EPIDs Based
      on Thick Pixelated Scintillating Crystals.
AB  - PURPOSE: One way to greatly reduce the incidence of metal artifacts produced in
      kilovoltage (kV) CT images is by using megavoltage (MV) photons that penetrate
      high-Z objects, thus providing a measurable signal. For do se-efficient imaging,
      a high detective quantum efficiency (DQE) MV detector is desired. This study
      validates the coupled radiation and optical Geant4 simulation results against
      experimental data from various prototype pixelated scintillator MV detectors and
      determines the essential optical parameters which control the detector
      performance. METHODS: Experimental data obtained with a 6MV radiation source from
      8 different detectors was considered. The detectors used CsI, CdW and BGO as
      scintillating crystals and polystyrene septal wall material. Accurate Geant4
      models of the detectors were implemented and coupled radiation and optical
      simulations were performed. The unknown optical properties of the models were
      determined by minimizing the difference between the modulation transfer functions
      (MTF) of the simulated data obtained with the slanted slit technique and the
      experimental MTFs. With the set of optical properties fixed, further simulation
      validation was performed against the experimental normalized noise power spectrum
      (NNPS(f)) and the experimental DQE(f) curves for each detector. All the
      simulations were performed on a computer cluster deployed on the Amazon EC2
      platform. RESULTS: The optimal values for the free optical parameters are 10%,
      95% and 90% for the top surface reflectivity, the crystal-sept a surface
      reflectivity, and the Lambertian component contribution to the reflected beam
      from the crystal-septa interface respectively. The absolute difference between
      experimental and simulated data was below 10% for all the data sets. CONCLUSIONS:
      To our knowledge this study is the first to present a full optical and radiative
      DQE(f) model using Geant4 that shows an excellent match with experimental data.
      The model indicates that improved performance can be obtained using more specular
      septa which are optically opaque. Support: NIH-T32-CA09695, NIH-1R01CA138426 NIH
      T32-CA09695, NIH R01- CA138426, Several authors work for Varian Medical Systems.

PMID- 28520012
TI  - WE-E-213CD-11: A New Automatically Generated Metric for Evaluating the Spatial
      Precision of Deformable Image Registrations: The Distance Discordance Metric.
AB  - PURPOSE: We propose a new metric called Distance Discordance (DD), which is
      defined as the distance between two anatomic points from two moving images, which
      are co-located on some reference image, when deformed onto another reference
      image. METHODS: To demonstrate the concept of DD, we created a reference software
      phantom which contains two objects. The first object (1) consists of a hollow box
      with a fixed size core and variable wall thickness. The second object (2)
      consists of a solid box of fixed size and arbitrary location. 7 different
      variations of the fixed phantom were created. Each phantom was deformed onto
      every other phantom using two B-Spline DIR algorithms available in Elastix and
      Plastimatch. Voxels were sampled from the reference phantom [1], which were also
      deformed from moving phantoms [2...6], and we find the differences in their
      corresponding location on phantom [7]. Each voxel results in a distribution of DD
      values, which we call distance discordance histogram (DDH). We also demonstrate
      this concept in 8 Head & Neck patients. RESULTS: The two image registration
      algorithms produced two different DD results for the same phantom image set. The
      mean values of the DDH were slightly lower for Elastix (0-1.28 cm) as compared to
      the values produced by Plastimatch (0-1.43 cm). The combined DDH for the H&N
      patients followed a lognormal distribution with a mean of 0.45 cm and std.
      deviation of 0.42 cm. CONCLUSIONS: The proposed distance discordance (DD) metric
      is an easily interpretable, quantitative tool that can be used to evaluate the
      effect of inter-patient variability on the goodness of the registration in
      different parts of the patient anatomy. Therefore, it can be utilized to exclude
      certain images based on their DDH characteristics. In addition, this metric does
      not rely on 'ground truth' or the presence of contoured structures. Partially
      supported by NIH grant R01 CA85181.

PMID- 28520013
TI  - WE-E-217BCD-01: Digital Breast Tomosynthesis: Basic Principles and the QMP's
      Role.
AB  - : Digital breast tomosynthesis is a form of limited angle tomography, in which
      section (slice) images are produced from a series of discrete projection images
      acquired at different angles. Tomosynthesis can be useful in breast imaging by
      providing potentially better visibility of lesions over conventional mammography,
      especially in patients with dense breasts. This talk will cover the various
      physics aspects of DBT, including reconstruction algorithms, the importance of
      deblurring, and optimizing image acquisition parameters. Remaining important
      research questions in DBT will be presented and discussed. The presentation will
      also discuss MQSA Certificate extension process for currently approved digital
      breast tomosynthesis (DBT) systems. Training requirements, manufacturer required
      tests for Mammography Equipment Evaluation (MEE) as acceptance tests, and phantom
      imaging for the purpose of approval of certificate extension will be described.
      The talk will emphasize the specific tests where special attention must be given
      and will discuss how the techs should be advised to perform these tests. LEARNING
      OBJECTIVES: 1. To understand the fundamentals of tomosynthesis reconstruction,
      including deblurring, algorithm choice, and optimization 2. To understand FDA's
      certificate extension process for DBT 3. To understand the requirements for MEE
      4. To understand the required AEC tracking data Research sponsored in part by
      NIH, Siemens, and GE Healthcare.

PMID- 28520014
TI  - WE-E-BRB-07: Direct 3D Fluence Calculation from Machine Beam Parameters for VMAT
      Delivery Verification.
AB  - PURPOSE: MLC dynamic log files have been clinically used for quality assurance
      for years. The logged machine parameters and the derived beam 2D fluence maps can
      be compared to the ones obtained in the treatment plans in order to evaluate the
      accuracy and consistency of IMRT beam deliveries. In this study, we propose a
      computationally efficient method, called Direct 3D Fluence Calculation or D3DFC,
      to extend 2D fluence map derivation to 3D fluence volume computation. The aim is
      to extend dynalog-based QA from fixed-gantry IMRT to rotational-gantry VMAT.
      METHODS: D3DFC calculates the 3D volume of photon fluence distribution directly
      from the machine parameters (gantry angles, jaw positions, MLC positions,
      collimator rotation angle, MU) contained in the dynamic log files or DICOM plans,
      without converting to 2D fluence maps per gantry angle in order to allow higher
      computation speed and accuracy. For testing, results were verified with film-in
      air measurements. 3D fluence volumes computed from VMAT delivery records (with
      artificially introduced delivery errors) are compared to ones computed from the
      treatment plans to determine if these delivery errors can be identified. RESULTS:
      D3DFC is implemented in MATLAB and supports the DICOM plans, Varian MLC dynamic
      logs and Varian Truebeam machine logs. Computation takes 10 to 20 seconds for a
      single-arc VMAT plan or delivery records. The results showed that 1 mm MLC errors
      can be clearly detected using delivery-to-plan fluence volume comparison.
      CONCLUSIONS: Direct computation from machine parameters allows higher computation
      speed and accuracy. These advantages are useful for beam delivery verification
      purposes for which (slower) full patient CT based dose computation is less
      necessary. The calculated 3D photon fluence volume is useful to detect and
      visually present the VMAT delivery discrepancies.

PMID- 28520015
TI  - WE-E-211-01: Medical Physics in Federal and State Governments.
AB  - : In 2010, FDA's Center for Devices and Radiological Health (CDRH) launched an
      "Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging" and
      held a public meeting on "Device Improvements to Reduce Unnecessary Radiation
      Exposure from Medical Imaging" March 30- 31, 2010). In follow-up, FDA is pursuing
      efforts using its regulatory authority as it applies to imaging equipment and
      manufacturers and also partnering with professional organizations such as AAPM,
      industry and other governmental agencies to incorporate radiation protection
      principles into facility quality assurance, personnel credentialing, and training
      requirements.The current U.S. Federal guidance on medical x-rays was published in
      1976 and addresses film imaging for radiographie and dental modalities. The
      Medical Workgroup of the Interagency Steering Committee on Radiation Standards
      (ISCORS) has modernized that document to address both diagnostic and
      interventional approaches, film and digital imaging, and the broad range of
      modalities that include radiography, computed tomography, interventional
      fluoroscopy, dentistry, bone densitometry, and veterinary practice. The current
      scope and status of the document will be presented.The Military Health System is
      committed to providing state-of- the-art care to its beneficiaries; both at home
      and abroad. Personnel constraints and the continuing wars oversees have created
      obstacles to this objective. In the past decade, tremendous advances have
      occurred in Electronic Health Records (EHR) and Teleradiology. Military Radiology
      seeks to leverage these advances as a means of surmounting many of the challenges
      it faces. In this talk, the current status of DoD teleradiology and EHR will be
      presented. LEARNING OBJECTIVES: 1. To provide a venue in which physicists working
      in the public sector can interface and discuss specific issues related to
      supporting the federal and state governments 2. To provide a venue for medical
      physicists to voice specific concerns with federal/state programs where medical
      physics should be involved in and/or more effective. 3. To educate audience on
      federal or state new or updated guidelines.

PMID- 28520016
TI  - WE-E-BRB-09: A GPU-Based Monte Carlo QA Tool for IMRT and VMAT.
AB  - PURPOSE: To develop a GPU-based Monte Carlo (MC) 3D dosimetry quality assurance
      (QA) tool employing patient geometry and actual delivery information. METHODS:
      First, we generate fluence maps at all beam angles from the initial treatment
      plan. A GPU-based MC dose engine, gDPM, is employed for the secondary dose
      calculation (SDC) on patient CT. This SDC is used to verify the TPS plan dose
      (PD) accuracy. Before the 1st treatment fraction, we deliver the treatment plan
      on a Linac without any phantom setup to obtain machine log files. With the log
      files, we extract actually delivered fluence maps at all beam angles and perform
      delivered dose calculation (DDC) using gDPM. The difference between DDC and SDC
      indicates possible errors in data transferring and machine delivery. Lastly, the
      comparison between DDC and PD shows the accumulative errors from all the possible
      sources. Moreover, a web application for this QA tool is developed for clinical
      use. We have tested this QA tool on 6 patients, 4 VMAT and 2 IMRT patients. We
      reported mean gamma values and passing rates inside the 20% isodose line; DVH
      plot and dose difference matrix are also documented. RESULTS: For all six
      patients, the gamma passing rates within the 20% isodose line for SDC, DDC and PD
      comparisons are all higher than 95%. In the DVH plot, the three dose
      distributions were found to be very close. A typical IMRT or VMAT case takes less
      than one minute to run the whole QA tool. CONCLUSIONS: We have developed a GPU
      based MC QA tool which can be used for efficient and easy IMRT and VMAT QA.

PMID- 28520017
TI  - WE-C-217BCD-06: In Vivo Targeting and Imaging of Tumor Vasculature with
      Radiolabeled, Antibody-Conjugated Nano-Graphene.
AB  - PURPOSE: Our goal was to explore nano-graphene for in vivo tumor targeting and
      quantitatively evaluate the pharmacokinetics and tumor targeting efficacy through
      PET imaging, using 6 4 Cu and 66 Ga as the radiolabel. METHODS: Nano-graphene
      oxide (GO) sheets, with amino group- terminated PEG chains (10 kDa) covalently
      attached, were conjugated to NOTA (l,4,7-triazacyclononane-l,4,7-triacetic acid,
      a suitable chelator for 6 4 Cu and 6 6 Ga) and TRC105 (a mAb that binds to CD
      105, overexpressed on neovasculature). FACS analyses, size measurements, and
      serum stability studies were performed to characterize the GO conjugates before
      in vivo investigation (PET, bio distribution, blocking studies, etc.) in 4T1
      murine breast tumor-bearing mice. Findings from imaging studies were then
      validated by histology. RESULTS: TRC105-conjugated GO, 20-30 nm in diameter, was
      specific for CD105 with little non-specific binding. Both 64 Cu- and 66 Ga-
      labled GO conjugates had excellent stability in mouse serum. Clearance of the GO
      conjugates in mice was via the hepatobiliary pathway. v Cu/6 6 Ga-NOTA-GO-TRC105
      accumulated rapidly in the 4T1 tumor and tumor uptake remained stable over time
      (3.8+/-0.4, 4.5+/-0.4, 5.8+/-0.3, and 4.5+/-0.4 %ID/g at 0.5, 3, 7, and 24 h p.i.
      for66 Ga; 5.8+/-0.6, 5.3+/-0.6, 4.0+/-0.4, and3.4+/-0.1 %ID/g at 0.5, 3,24, and
      48 h p.i. for 6 4 Cu; n = 4). Blocking studies confirmed CD105 specificity of 6 4
      Cu/6 6 Ga-NOTA- GOTRC105, which was corroborated by bio distribution studies.
      Furthermore, microscopy examination of GO in light view mode and
      immunofluorescence staining revealed that targeting of NOTA-GO-TRC105 is tumor
      vasculature CD105 specific with little extravasation. CONCLUSIONS: For the first
      time, we demonstrated that GO can be specifically directed to the tumor
      neovasculature in vivo through targeting of CD105, a marker of tumor
      angiogenesis. The versatile chemistry of graphene-based nanomaterials makes them
      suitable nanoplatforms for future biomedical research, such as cancer
      theranostics.

PMID- 28520018
TI  - WE-E-213CD-06: A Locally Adaptive, Intensity-Based Label Fusion Method for Multi-
      Atlas Auto-Segmentation.
AB  - PURPOSE: Atlas-based auto-segmentation (ABAS) has emerged as a very useful
      contouring tool for radiotherapy planning. Higher accuracy of ABAS typically
      requires the use of multiple atlases, for which the final label fusion step is a
      key design component. This work presents a novel locally adaptive, intensity
      based label fusion approach for multi-atlas ABAS, and compares its performance
      against the commonly used STAPLE method. METHODS: The label fusion method derives
      the final structure label for a novel patient image as a weighted average of
      several warped atlas label maps, where the atlas warping is achieved through
      deformable atlas registration. Instead of assigning a constant global weighting
      factor for each atlas and for each structure, adaptive weights are computed at
      each image location based on the local correlation coefficients (LCC) computed
      between the patient image and each warped atlas image. To compensate for
      registration errors, neighboring atlas labels within a small distance from the
      center point are also considered in the fusion computation, but only the first k
      (typically 25) neighbors with the largest LCC are included to get better
      accuracy. The method was evaluated using ten manually contoured H&N patient
      images with a leave-one-out validation strategy. Performances of the newly
      proposed method and the classical STAPLE method are compared for 7 structures
      including the mandible, the parotids (left and right), the sub- mandibular glands
      (left and right), the brainstem, and the spinal cord. RESULTS: The proposed
      intensity-based label fusion method significantly outperforms the STAPLE method
      for all structures considered. The improvement of the mean Dice value ranges from
      1.5%for the right parotid to 9% for the right sub-mandibular gland. CONCLUSIONS:
      The locally adaptive, intensity-based label fusion provides a superior accuracy
      compared to the STAPLE method, which helps boost the performance of ABAS methods
      and make them more usefulness in practice. The author is a current employee of
      Elekta Inc.

PMID- 28520019
TI  - WE-C-218-01: Ultrasound Contrast Agents.
AB  - : Medical ultrasound has long been used in clinical applications both as a
      primary modality and as a supplement to other diagnostic procedures. The basis
      for ultrasound imaging is the transmission of high frequency (megaHertz) sound
      waves that propagate through tissue. These sound waves backscatter from the
      interfaces between tissue components with different acoustic properties and are
      detected by the imaging system, allowing the creation of images based on tissue
      characteristics and spatial location. Thus, traditional ultrasound has focused
      primarily on the imaging of anatomical structures and analysis of blood flow in
      large vessels. Unfortunately, blood is a weak scatterer, which can make vascular
      diagnostic applications (example: echocardiography) challenging especially with
      larger patients. Contrast agents help to improve on this shortcoming by enhancing
      the visualization of blood flow, thus improving the quality of diagnostics. The
      use of contrast agents for ultrasound was first reported in 1968 when Gramiak and
      Shah discovered that there was an increased backscatter of ultrasound caused by
      injected microbubbles. This is because the mismatch in acoustic impedance (a
      function of an object's density and compressibility) between the microbubble gas
      core and blood (or tissue) is several orders of magnitude, which results in
      substantially higher scattering from a bubble than an equivalent volume of tissue
      or blood. Additionally, microbubbles oscillate in response to an ultrasound
      field, and respond non-linearly to acoustic pulses even at low energies, unlike
      tissue. The non-linear property of microbubbles in an ultrasound field allows for
      the use of various pulsing and signal processing strategies to detect the
      backscattered signal from contrast agents and segment it from tissue, thus
      providing a high contrast-to- noise ratio. Due to these unique acoustic
      properties, a clinical ultrasound system can detect even single microbubble
      contrast agents, providing exquisite sensitivity and the ability to perform
      advanced diagnostic procedures. Over the last several decades, ultrasound
      contrast agents have been improved for enhanced stability and increased
      persistence times. Although preclinical studies as well as clinical use in Europe
      and Asia strongly suggest that the use of contrast ultrasound can substantially
      improve diagnostic capabilities in both cardiology and radiology applications,
      contrast use in the US is still very limited. Obstacles to the widespread use of
      microbubbles include safety concerns, the need for optimization of approaches for
      contrast use, and general understanding of their potential by physicians. This
      course covers the basic principles of contrast agents used in ultrasound imaging
      including their stability, shell properties and their behavior within an acoustic
      field. In addition, we will cover many new techniques that are being evaluated in
      preclinical studies including: p er fus ion-based techniques, molecular imaging,
      gene therapy, drug delivery, and acoustic angiography. Finally, basic safety
      concerns and biological effects will be reviewed. LEARNING OBJECTIVES: 1.
      Understand the basic principles of ultrasound contrast agents a. What are
      microbubble contrast agents? b. Properties of microbubbles c. Safety concerns and
      biological effects 2. Understand basic contrast imaging techniques a. Harmonic
      and suharmonic imaging techniques b. Pulse inversion techniques 3. Understand the
      use of contrast agents in various vascular applications a. Traditional methods
      (Cardiovascular, Abdominal) b. Advanced perfusion imaging techniques 4.
      Understand the role of contrast agents in preclinical applications a. Ultrasound
      molecular imaging b. Gene therapy c. Drug delivery d. Acoustic angiography.

PMID- 28520020
TI  - WE-F-211-01: The Evolving Landscape of Scientific Publishing.
AB  - : The dissemination of scientific advances has changed little since the first
      peer-reviewed journal was published in 1665 - that is, until this past decade.
      The print journal, delivered by mail and stored on office shelves and in library
      reading rooms around the world, has been transformed by immediate, on-demand
      access to scientific discovery in electronic form. At the same time, the
      producers and consumers of that scientific content have greatly increased in
      number, and the balance between supply and demand has required innovations in the
      world of scientific publishing. In light of technological advances and societal
      expectations, the dissemination of scientific knowledge has assumed a new form,
      one that is dynamic and rapidly changing. The academic medical physicist must
      understand this evolution to ensure that appropriate decisions are made with
      regard to journal submission strategies and that relevant information on new
      findings is obtained in a timely manner. Medical Physics is adapting to these
      changes in substantive ways. This new scientific publishing landscape has
      implications for subscription models, targeted access through semantic
      enrichment, user interactivity with content, customized content delivery, and
      advertising opportunities. Many organizations, including the AAPM, depend on
      scientific publishing as a significant source of revenue, but web-based delivery
      raises the expectation that access should be free and threatens this model. The
      purpose of this symposium is to explore the factors that have contributed to the
      current state of scientific publishing, to anticipate future directions in this
      arena, and to convey how medical physicists may benefit from the expanded
      opportunities, both as authors and as readers. LEARNING OBJECTIVES: 1. To
      appreciate the importance of scientific and clinical practice communication for
      the advancement of the medical physics field 2. To understand the roles of the
      Editorial Board and the Journal Business Management Committee in the promotion
      and advancement of Medical Physics 3. To explore technology-driven content
      delivery mechanisms and their role in facilitating content access and driving
      content usage 4. To understand the potential benefits and pitfalls of various
      economic and editorial models of scientific publications and the recent shifts
      away from the traditional role of libraries.

PMID- 28520021
TI  - WE-E-BRB-02: Evaluation of Analytical Proton Dose Predictions with a Lung-Like
      Plastic Phantom.
AB  - PURPOSE: Former studies have shown that in homogeneities in the path of
      therapeutic proton beams can lead to a degradation of the distal edge of the
      Bragg peak. These studies mostly investigated bone-air interfaces. This study
      focuses on distal edge degradation caused by finely structured soft tissue - air
      interfaces, which can be found in lung tissue. METHODS: A randomly filled
      voxelized lung-like phantom was designed and produced using rapid prototyping
      methods. The results of transmission measurements on this phantom were used to
      validate Monte Carlo (MC) calculations, which were then used as gold standard to
      calculate doses in several lung equivalent geometries (phantoms). The results
      were compared to the results of analytical dose calculation engines. RESULTS:
      Transmission measurements showed that the distal falloff width (from 90 % of the
      peak dose to 10 %) in water increased from 3.32 mm by 117 % to 7.19 mm for an
      initial proton energy of 140 MeV, and from 5.95 mm to 9.03 mm (52 %) for 200 MeV.
      The peak dose in the degraded beam was only 70 % (for 140 MeV) and 84 % (for 200
      MeV) of the value observed in non-degraded beams. These findings were in contrast
      to the results obtained with analytical dose computation engines, but are in
      agreement with MC calculations. CONCLUSIONS: If not predicted correctly, Distal
      Edge Degradation in lung cancer therapy can lead to severe under-dosage of the
      target region and unwanted dose in organs at risk distal to the Bragg peak.
      Therefore clinically used dose calculation algorithms have to be extended to take
      lateral in homogeneities into account.

PMID- 28520022
TI  - WE-E-BRA-02: Optimization of Functional MRI Techniques for Assessment of Tumor
      and Normal Tissue Response to RT.
AB  - : The advantages of physiological and functional MRI for radiation treatment
      assessment of tumor response and normal tissue damage for adaptive RT as well as
      for boost target definition are well recognized. However, several limitations of
      functional MRI have hindered its wide application in radiation therapy, including
      concerns about optimal pulse sequence parameters, high resolution volumetric
      acquisition, acquisition speed, motion-sensitivity, reproducibility, and image
      processing. Many of these shortcomings have been overcome or will be overcome by
      standardization of image acquisition and quantification. It is also important to
      understand sensitivity and specificity of these imaging techniques for particular
      clinical questions. This lecture will provide an overview on these techniques and
      issues. Examples of applying these techniques to liver and prostate will be
      given. LEARNING OBJECTIVES: 1. Understand new MRI technologies that are relevant
      to radiation treatment assessment; 2. Understand the influence of imaging
      parameters on image quality and contrast; 3. Understand image processing
      techniques for derived quantitative parameters; 4. Understand clinical
      applications and limitations. Author's work is supported in part by NIH P01
      CA59827, NCI RO1 CA132834, and RO1 NS064973. 3959.

PMID- 28520023
TI  - WE-C-217BCD-10: Development of High Performance PET for Animal Imaging and
      Therapy Applications.
AB  - PURPOSE: A prototype small animal PET is developed with several novel
      technologies to measure 3D gamma-interaction positions and to substantially
      improve imaging performance. METHODS: Each new detector has an 8*8 array of
      1.95*1.95*30 mm3 LYSO scintillators, with each end optically connected to a solid
      state photo multiplier (SSPM) array through a light guide. This dual-ended
      readout enables the depth-of-interaction (DOI) measurement. Each SSPM array has
      16 SSPMs arranged in a 4*4 matrix. Each SSPM has active area about 3*3 mm2, with
      its output read by an ASIC electronics that directly converts analog signals to
      digital timing pulses which encode the interaction information for energy,
      timing, crystal of interaction, and DOI calculations. These digital pulses are
      transferred to and decoded by FPGA-based TDC for coincident event selection and
      data acquisition. This independent readout of each SSPM and parallel signal
      process significantly improve signal-to-noise ratio and permit applying flexible
      data processing algorithms. The current prototype system consists of two rotating
      detector panels on a portable gantry, with 4 detectors linearly packed together
      in each panel to provide ~16 mm axial and variable trans- axial FOV with
      adjustable panel-to-panel distance. List-mode OSEM-based image reconstruction
      with resolution modeling was implemented. Both Na- 22 point source and phantom
      were used to evaluate the system performance. RESULTS: The measured energy,
      timing, spatial and DOI resolutions for each crystal were around 16%, 2.6 ns, 2.0
      mm and 5.0 mm, respectively. The measured spatial resolutions with DOI were ~1.7
      mm across the entire FOV in all direction, while those without DOI were much
      worse and non-uniform across the FOV, in the range predominately around 3.0 to
      4.0 mm. In addition, images from a F-18 hot-rod phantom with DOI show
      significantly improved quality compared to those without DOI. CONCLUSIONS: DOI-
      measurable PET shows substantially improved image performance for a compact
      system. National Institute of Health. University of Texas MD Anderson Cancer
      Center.

PMID- 28520024
TI  - WE-E-213CD-10: A Robust 2D/3D Image Registration System for Pediatric Patient
      Setup in External Beam Radiotherapy.
AB  - PURPOSE: To develop a neural network based registration quality evaluator (RQE)
      that can improve the 2D/3D image registration robustness for pediatric patient
      setup in external beam radiotherapy. METHODS: X-ray setup images of six pediatric
      patients with brain tumors received proton therapies were retrospectively
      registered with their treatment planning computed tomography (CT) images. A
      neural network based pattern classifier was used as an RQE to classify 2D/3D
      rigid registration solutions as successful or unsuccessful based on features of
      the similarity value surfaces near the point-of-solution. The supervised training
      and test datasets were generated by rigidly registering a pair of orthogonal
      daily setup x-ray images to the treatment planning CTs. The best solution for
      each registration task was selected from 50 optimizing attempts that differed
      only by the initial transformation parameters. The distance from each individual
      solution to the best solution in the normalized parametrical space was compared
      to a user- defined error threshold to determine whether that solution was
      successful. The supervised training was then used to train the RQE. The
      performance of the RQE was evaluated using the test dataset that consisted of
      registration results that were not used in training. RESULTS: With the optimized
      sampling step size, i.e., 5 mm, in the feature space, the RQE has the sensitivity
      and the specificity in the ranges of 0.865-0.964 and 0.797-0.990, respectively,
      when it was used to detect the registration error with the mean voxel
      displacement (MVD) greater than 1 mm. CONCLUSIONS: The proposed RQE can
      potentially be used in a 2D/3D rigid image registration system to improve its
      robustness by rejecting unsuccessful registration solutions. The RQE is non
      patient specific and needs only to be trained once for each treatment site. The
      implementation the RQE in a 2D/3D registration system results only 10% to 20%
      increase of the overall computation time. The authors have no conflict of
      interest to disclose.

PMID- 28520084
TI  - Renal and hematologic side effects of long-term intravenous immunoglobulin
      therapy in patients with neurologic disorders.
AB  - INTRODUCTION: For patients receiving intravenous immunoglobulin (IVIg), renal and
      hemolytic side effects are well recognized. However, there are very few data on
      the effects of chronic IVIg therapy. METHODS: We retrospectively analyzed
      laboratory data on 166 patients who received IVIg for 12 months with a dose range
      of 0.441-2.58 g/kg/month, measuring changes in hematocrit and glomerular
      filtration (GFR) rates at 6 and 12 months. RESULTS: Of the 2,232 infusions, there
      were no incidents of clinical hemolysis. However, after 12 months of treatment,
      21% of patients had a >=3-g/dl decline in hematocrit and 10% had a >=20% decline
      in GFR. DISCUSSION: No clinically significant hemolysis was observed in patients
      receiving chronic IVIg therapy. However, a significant number of patients had a
      decline in hematocrit and/or GFR while on therapy. This emphasizes the need for
      observation of hematologic and renal function in patients treated with chronic
      IVIg. Muscle Nerve 56: 1173-1176, 2017.

PMID- 28520085
TI  - Assessment of the Relationship between Body Mass Index and Incidence of Venous
      Thromboembolism in Hospitalized Overweight and Obese Patients.
AB  - STUDY OBJECTIVE: To assess whether a positive linear association exists between
      body mass index (BMI) and incidence of venous thromboembolism (VTE) in overweight
      and obese hospitalized patients. DESIGN: Single-center retrospective
      observational cohort study. SETTING: Large academic tertiary care medical center.
      PATIENTS: A total of 1452 adults hospitalized between January 1, 2013, and
      December 31, 2014, who weighed more than 100 kg and had a BMI of 25 kg/m2 or
      greater on admission, and received heparin subcutaneously for VTE prophylaxis.
      Patients were categorized into four subgroups based on World Health Organization
      BMI classification: overweight (141 patients), obese class I (305 patients),
      obese class II (324 patients), and obese class III (682 patients). MEASUREMENTS
      AND MAIN RESULTS: The primary outcome was occurrence of VTE in each subgroup; all
      cause mortality and length of hospital stay were secondary outcomes. A linear
      trend test did not show an association between occurrence of VTE and BMI of 25
      kg/m2 or greater. VTE occurred in 7 (5%) of 141 patients in the overweight group,
      5 (2%) of 305 in the obese class I group, 8 (3%) of 324 in the class II group,
      and 18 (3%) of 682 in the class III group (p=0.573). In addition, no linear
      association was noted between all-cause mortality or length of hospital stay and
      BMI of 25 kg/m2 or greater. Overall mortality was 10% (146/1452 patients). Ten
      deaths (7%) occurred in the overweight group, 45 (15%) in the obese class I
      group, 38 (12%) in the obese class II group, and 53 (8%) in the obese class III
      group (p=0.067). The median length of hospital stay was 5 days (interquartile
      range 3-9, p=0.122) for all patients. CONCLUSION: In overweight and obese
      hospitalized patients who weighed more than 100 kg and had a BMI of 25 kg/m2 or
      greater, the incidence of VTE did not increase incrementally with increasing
      severity of obesity.

PMID- 28520086
TI  - Activated FGFR3 prevents subchondral bone sclerosis during the development of
      osteoarthritis in transgenic mice with achondroplasia.
AB  - The purpose of this study is to investigate the morphometric changes of the
      subchondral bone during the development of osteoarthritis (OA) in transgenic mice
      with achondroplasia (Fgfr3ach ) carrying a heterozygous gain-of-function mutation
      in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and
      surgically induced by destabilization of the medial meniscus: The DMM model) were
      established. Articular cartilage, epiphysis, and metaphysis of the knee joint
      were histologically and morphometrically compared between wild-type mice, and
      Fgfr3ach mice in both OA models. Articular cartilage degeneration was scored
      according to the Osteoarthritis Research Society International (OARSI) scoring
      system. Several morphometric parameters including bone mineral density (BMD),
      bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and
      subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were
      quantified by micro-computed tomography (CT). In the aging model, although there
      were no significant differences in the OARSI score between wild-type mice and
      Fgfr3ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in
      wild-type mice. In the DMM model, the OARSI score of the medial compartment was
      significantly lower in Fgfr3ach mice than in wild-type mice. BMD, BV/TV, and
      Tb.Th in the epiphysis increased in wild-type mice and unchanged in Fgfr3ach
      mice, and the Sb.Th med was significantly larger in wild-type mice after surgery.
      Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited
      in Fgfr3ach mice. Activated FGFR3 signaling prevented sclerotic changes of the
      subchondral bone and subsequent cartilage degeneration. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:300-308,
      2018.

PMID- 28520088
TI  - Clathrin-mediated endocytosis is required for ANE 30-100K-induced autophagy.
AB  - BACKGROUND: We identified an autophagy-inducing areca nut (AN) ingredient (AIAI)
      in the 30-100 kDa fraction of AN extract (ANE 30-100K). This study was to analyze
      the role of endocytosis in ANE 30-100K-induced autophagy. METHODS: We used benzyl
      alcohol, dynasore, and shRNA of clathrin and dynamin to assess whether ANE 30
      100K-induced cytotoxicity and accumulation of microtubule-associated protein 1
      light chain 3 (LC3)-II were affected in oral (OECM-1) and esophageal (CE81T/VGH)
      carcinoma cells. RESULTS: Both benzyl alcohol and dynasore effectively reduced
      ANE 30-100K-induced cytotoxicity and LC3-II accumulation in OECM-1 and CE81T/VGH
      cells. Downregulated protein expression of both clathrin and dynamin by their
      shRNA also significantly attenuated ANE 30-100K-induced elevation of LC3-II
      levels in CE81T/VGH cells. CONCLUSIONS: These results indicate that AIAI may be
      engulfed by cells through clathrin-mediated endocytosis, which promotes the
      execution of the following autophagy program.

PMID- 28520087
TI  - Geographic variation and risk factors for systemic and limb ischemic events in
      patients with symptomatic peripheral artery disease: Insights from the REACH
      Registry.
AB  - BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are at high
      risk of ischemic events. However, data about predictors of this risk are limited.
      HYPOTHESIS: We analyzed baseline characteristics and 4-year follow-up of patients
      enrolled in the international REduction of Atherothrombosis for Continued Health
      (REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic
      attack to describe annual rates of recurrent ischemic events globally and
      geographically. METHODS: The primary outcome was systemic ischemic events
      (composite of cardiovascular death, myocardial infarction, or stroke) at 4 years.
      The secondary outcome was limb ischemic events (composite of lower limb
      amputation, peripheral bypass graft, and percutaneous intervention for PAD) at 2
      years. Multivariate analysis identified risk factors associated with recurrent
      ischemic events. RESULTS: The primary endpoint rate reached 4.7% during the first
      year and increased continuously (by 4%-5% each year) to 17.6% by year 4, driven
      mainly by cardiovascular mortality (11.1% at year 4). Japan experienced lower
      adjusted ischemic rates (P < 0.01) vs North America. Renal impairment (P < 0.01),
      congestive heart failure (P < 0.01), history of diabetes (P < 0.01), history of
      myocardial infarction (P = 0.01), vascular disease (single or poly, P < 0.01),
      and older age (P < 0.01) were associated with increased risk of systemic ischemic
      events, whereas statin use was associated with lower risk (P = 0.03). The limb
      ischemic event rate was 5.7% at 2 years. CONCLUSIONS: Four-year systemic ischemic
      risk in patients with PAD and no history of stroke or transient ischemic attack
      remains high, and was mainly driven by cardiovascular mortality.

PMID- 28520089
TI  - Observational study investigating tooth extraction and the shortened dental arch
      approach.
AB  - The shortened dental arch (SDA) provides a cost-effective dentition, considering
      the population is ageing and retaining teeth for longer. The aims were to observe
      the reasons and sites of tooth extraction and assess the functional dentition
      over 15 years in dental practice. Subjects were recruited who required permanent
      tooth extractions between 2000 and 2015. The reasons for extractions were chosen
      from twelve extraction codes. Data were also collected for demographics, tooth
      position, root treated teeth and functional pairs remaining. Patient-centred
      factors on reasons for tooth extraction and comments on chewing ability and
      aesthetics following extractions were recorded. Nine hundred and fifty-one teeth
      were extracted in 900 patients. The mean age was 60 years (SD 20, SE 7, 95% CI
      46, 74). Reasons for extraction were periodontal disease (n = 361, 38%),
      periapical infection (n = 288, 34%) or tooth and tooth-root fractures (15%).
      Extractions included 201 (21%) second molars, 179 (19%) first molars, 152 (16%)
      second premolars, 95 (10%) first incisors, 86 (9%) second incisors, 76 (8%)
      canines and 67 (7%) first premolars. Following extractions, median functional
      pairs were 12, interquartile range (IQR) 19-7. Individuals with >=10 functional
      pairs including anterior teeth (60%, n = 571) had no complaints with chewing
      ability or aesthetics. They did not require additional prostheses. Periodontal
      disease and periapical infection were the main causes for the extraction. First
      and second molars followed by second premolars were the most commonly extracted
      teeth. This study supports the SDA in creating a cost effective, functional
      dentition in an aging population, provided remaining teeth and restorations are
      preserved/maintained, oral health is promoted, and anterior aesthetic tooth
      replacement is ensured.

PMID- 28520090
TI  - Robotic ventral mesh rectopexy - a video vignette.

PMID- 28520091
TI  - Selective analysis of aristolochic acid I in herbal medicines by dummy
      molecularly imprinted solid-phase extraction and HPLC.
AB  - In this study, surface molecularly imprinted polymers were prepared as the
      selective sorbents for separation of aristolochic acid I in herbal medicine
      extracts by a facile approach. A less toxic dummy template, ofloxacin, was used
      to create specific molecule recognition sites for aristolochic acid I in the
      synthesized polymers. The polymers were characterized by Fourier-transfer
      infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis,
      elemental analysis, and nitrogen adsorption-desorption test. The adsorption
      capacity was calculated using adsorption kinetics, selectivity, and recycling
      experiments. The obtained polymers exhibited high thermostability, fast
      equilibrium time, and excellent binding ability. Subsequently, the polymers
      applied as the solid-phase extraction absorbent was proposed and used for the
      enrichment and analysis of aristolochic acid I in herbal plants. The result
      showed that the aristolochic acid I was enriched up to 16 times after analysis by
      using high-performance liquid chromatography. The good linearity for aristolochic
      acid I was obtained in the range of 0.1-200 MUg/mL (R2  = 0.9987). The recovery
      and precision values were obtained (64.94-77.73%, RSDs% <= 0.8%, n = 3) at three
      spiked concentration levels. This work provided a promising method for selective
      enrichment, extraction, and purification of aristolochic acid I from complex
      herbal plants.

PMID- 28520092
TI  - Mushrooms as Efficient Solar Steam-Generation Devices.
AB  - Solar steam generation is emerging as a promising technology, for its potential
      in harvesting solar energy for various applications such as desalination and
      sterilization. Recent studies have reported a variety of artificial structures
      that are designed and fabricated to improve energy conversion efficiencies by
      enhancing solar absorption, heat localization, water supply, and vapor
      transportation. Mushrooms, as a kind of living organism, are surprisingly found
      to be efficient solar steam-generation devices for the first time. Natural and
      carbonized mushrooms can achieve ~62% and ~78% conversion efficiencies under 1
      sun illumination, respectively. It is found that this capability of high solar
      steam generation is attributed to the unique natural structure of mushroom,
      umbrella-shaped black pileus, porous context, and fibrous stipe with a small
      cross section. These features not only provide efficient light absorption, water
      supply, and vapor escape, but also suppress three components of heat losses at
      the same time. These findings not only reveal the hidden talent of mushrooms as
      low-cost materials for solar steam generation, but also provide inspiration for
      the future development of high-performance solar thermal conversion devices.

PMID- 28520093
TI  - Verticillium dahliae transcription factor VdFTF1 regulates the expression of
      multiple secreted virulence factors and is required for full virulence in cotton.
AB  - Fungal transcription factors (TFs) implicated in the regulation of virulence gene
      expression have been identified in a number of plant pathogens. In Verticillium
      dahliae, despite its agricultural importance, few regulators of transcription
      have been characterized. In this study, a T-DNA insertion mutant with
      significantly reduced virulence towards cotton was identified. The T-DNA was
      traced to VdFTF1, a gene encoding a TF containing a Fungal_trans domain.
      Transient expression in onion epidermal cells indicated that VdFTF1 is localized
      to the nucleus. The VdFTF1-deletion strains displayed normal vegetative growth,
      mycelial pigmentation and conidial morphology, but exhibited significantly
      reduced virulence on cotton, suggesting that VdFTF1 is required exclusively for
      pathogenesis. Comparisons of global transcription patterns of wild-type and
      VdFTF1-deletion strains indicated that VdFTF1 affected the expression of 802
      genes, 233 of which were associated with catalytic processes. These genes encoded
      69 potentially secreted proteins, 43 of which contained a carbohydrate enzyme
      domain known to participate in pathogenesis during infection of cotton. Targeted
      gene deletion of one VdFTF1-regulated gene resulted in significantly impaired
      vascular colonization, as measured by quantitative polymerase chain reaction, as
      well as aggressiveness and symptom severity in cotton. In conclusion, VdFTF1,
      which encodes a TF containing a Fungal_trans domain, regulates the gene
      expression of plant cell wall degradation enzymes in V. dahliae, which are
      required for full virulence on cotton.

PMID- 28520094
TI  - Regulatory disorders in early childhood: Correlates in child behavior, parent
      child relationship, and parental mental health.
AB  - According to the guidelines published by the German Society of Child and
      Adolescent Psychiatry, Psychosomatics and Psychotherapy (2007), regulatory
      disorders of early childhood are characterized by a symptom triad, including (a)
      behavioral symptoms such as excessive crying, sleeping, or feeding problems; (b)
      a disturbed parent-child relationship; and (c) parental psychopathology. On the
      basis of a clinic-referred sample of 162 children, we examined whether children
      with and without regulatory symptoms differed in the quality of parent-child
      relationship and parental mental health, and how often the criteria of the
      symptom triad were fulfilled in the group of children with regulatory symptoms.
      In addition, emotional and behavior problems were compared in children with and
      without regulatory symptoms. Children with regulatory symptoms and children with
      other psychiatric symptoms did not differ with respect to child-parent
      relationship quality. However, parents of children with regulatory symptoms
      scored higher on the Symptom Checklist 90 Items-Revised (G.H. Franke, 2002) than
      did the other parents. On the Child Behavior Checklist (T.M. Achenbach & L.A.
      Rescorla, 2000), children with regulatory symptoms tended to show more somatic
      problems, but they showed significantly less withdrawn behavior than did the
      other children. Of the 67 children with regulatory symptoms, only 11 (16.4%)
      fulfilled all three criteria of a regulatory disorder.

PMID- 28520095
TI  - A quantitative psychometric evaluation of an intervention for poor dietary
      variety in children with a feeding problem of clinical significance.
AB  - Few studies have been published that offer a quantitative evaluation of
      interventions for feeding problems of clinical significance. Twenty-four children
      referred to the service for clinically significant feeding problems were
      administered the Behavioral Pediatric Feeding Assessment Scale (BPFAS; W. Crist &
      A. Napier-Phillips, 2001) and the Child Feeding Assessment Questionnaire (CFAQ;
      G. Harris & I.W. Booth, 1992) before and after a duel targeted 16-week
      therapeutic intervention to improve dietary variety. Dietary variety was assessed
      through a food diary where only items that were accepted on more than one
      occasion were deemed to be part of the child's habitual diet. Results indicated
      that all subscales of the BPFAS and the CFAQ were responsive to the intervention,
      with scores falling from those of clinical significance to those more
      representative of non-feeding-problem children. Regression analysis indicated
      that children's problem scores on the BPFAS predicted 15% of the variance in
      increased dietary variety following the intervention. The outcome of this
      evaluation indicated that improving dietary variety in children with clinically
      significant feeding problems is challenging. With the right approach, however,
      large improvements can be observed relatively quickly.

PMID- 28520096
TI  - A randomized control trial of integrated care for families managing infant colic.
AB  - This article presents a randomized clinical trial examining the effectiveness of
      a unique model of integrated care for the treatment of infant colic. Families
      seeking help for infant colic were randomized to either the family-centered
      treatment (TX; n = 31) or standard pediatric care (SC; n = 31). All parents
      completed 3 days of Infant Behavior Diaries (Barr et al., 1998) and the Colic
      Symptom Checklist (Lester, 1997), Beck Depression Inventory (Beck & Steer, 1984),
      and Parenting Stress Index 3rd ed.-SF (Abidin, 1995). TX families were seen three
      times by a pediatrician and a mental health clinician within 1, 2, and 6 weeks of
      baseline data. TX families received individualized treatment plans addressing
      problem areas of sleep, feeding, routine, and family mental health. SC families
      were seen only by their own healthcare provider. All families were visited at
      home by a research assistant to retrieve data at 2, 6, and 10 weeks after
      baseline. Family-based treatment accelerated the rate of reduction of infant
      crying faster than did standard pediatric care. Infants in the TX group had more
      hours of sleep at 2 weeks posttreatment and spent less time feeding at 2, 6, and
      10 weeks posttreatment than did SC infants. Results indicate that individualized
      family-based treatment reduces infant colic more rapidly than does standard
      pediatric care.

PMID- 28520097
TI  - Depressive-symptom onset during toddlerhood in a sample of depressed
      preschoolers: Implications for future investigations of major depressive disorder
      in toddlers.
AB  - This study investigated the occurrence of depressive symptoms prior to age 36
      months as retrospectively reported by parents of preschoolers with clinical
      depression. The study provides some of the first empirical data on the
      manifestations of depressive symptoms during the toddler period, advancing
      existing theoretical and case-report literature. A sample of 301 (depressed,
      disruptive, and healthy) children between the ages of 3.0 and 6.0 years were
      screened and oversampled for depressive symptoms from community sites. Primary
      caregivers (parents) were interviewed about their child's symptoms of depression
      (as well as other symptoms of mental disorders and developmental parameters), and
      age of first onset of depressive symptoms was ascertained. Findings suggest that
      clinical-level symptoms of depression may arise as early as age 24 months. The
      domain of negative self-concept during the toddler period evidenced by self
      deprecation and difficulty making choices emerged as the two strongest variables
      predictive of preschool depression. Our results suggest that prospective
      empirical studies of depressive symptoms in children younger than 3 years of age
      should now be undertaken.

PMID- 28520098
TI  - Development of regulation disorders into specific psychopathology.
AB  - Underlying deficits in self-regulation and sensory processing are seen in
      children with regulation disorders (RD) and might lead to emotional and
      behavioral problems as the child develops. However, little is known about the
      specific developmental course of RD. This follow-up study was conducted to
      investigate the development of a clinical sample of RD children, diagnosed by
      means of the Diagnostic Classification of Mental Health and Developmental
      Disorders of Infancy and Early Childhood, Revised (DC:0-3R; ZERO TO THREE, 1994),
      toward specific psychopathology 4 to 10 years later based on parent- and teacher
      reports on the Child Behavior Checklist (T.M. Achenbach & L.A. Rescorla, 2007).
      Parental reports showed that 39 to 69% of children with RD had internalizing,
      externalizing, and total problems above borderline cutoffs, as compared to norm
      group data (16%). In addition, higher rates of affective, anxiety, attention
      deficit/hyperactivity, oppositional defiant, and conduct problems were reported.
      Analyses between RD subtypes showed significant differences on future attention
      problems and rule-breaking behavior, wherein less favorable results were found
      for the Hypersensitive subtype Type A (fearful/cautious) in comparison to the
      sensory stimulation-seeking/impulsive subtype. The current results indicate
      persistence of emotional and behavioral problems into middle childhood and
      adolescence in children with preschool RD diagnoses. More attention should be
      paid to differentiation of psychopathology in these children since developmental
      outcomes may differ between RD subtypes.

PMID- 28520099
TI  - Maternal representations and emotional availability among drug-abusing and
      nonusing mothers and their infants.
AB  - Both negative and idealized maternal prenatal representations may constitute a
      risk for mother-infant interaction. This study analyzed the role of maternal
      prenatal representations and pre- to postnatal representational change in
      predicting mother-infant emotional availability (EA) among 51 drug-abusing
      mothers and their infants who participated in either psychodynamic group therapy
      (PGT) or received psychosocial support (PSS) and among 50 nonusing comparison
      dyads. Maternal representations of her child, the child's father, her own mother,
      self-as-mother, and self-as-woman were measured during pregnancy and at 4 and 12
      months' postpartum with the Interview of Maternal Representations (M. Ammaniti et
      al., 1992; M. Ammaniti, R. Tambelli, & P. Perucchini, 1998). EA was measured with
      the Emotional Availability Scales, fourth edition (Z. Biringen, 2008) at 4 and 12
      months. The results showed that drug-abusing mothers had more negative prenatal
      representations of the self-as-woman and of the child's father. Postnatally, PSS
      mothers tended to first idealize their child, but later to experience
      disillusionment of idealization. Both negative and idealized prenatal
      representations of the self-as-mother predicted mother-infant EA problems, but
      only among the PGT mothers. For all mothers, negative representational change was
      detrimental for the mother-infant EA whereas for drug-abusing mothers, also
      increasing idealization from the prenatal period to the postnatal period was
      harmful. Clinicians working with drug-abusing mothers should aim at supporting
      the development of a realistically positive view of motherhood.

PMID- 28520100
TI  - Early childhood trichotillomania: Initial considerations on phenomenology,
      treatment, and future directions.
AB  - Historically, trichotillomania (TTM) in young children (0-3 years old) generally
      has been considered to be a benign habit that is clinically distinct from the TTM
      seen in older children and adults. However, early childhood TTM can be an
      impairing pathological disorder that merits formal intervention. The present
      article reviews the extant literature on TTM in young children, highlighting the
      limited available phenomenological data. We discuss a behavioral approach to
      conceptualization and treatment, highlighting core intervention strategies in
      three early childhood TTM cases seen in our clinic. We conclude by discussing
      areas in need of further empirical attention.

PMID- 28520101
TI  - Transition and moving forward.

PMID- 28520102
TI  - Etiology of preschool behavior problems: Contributions of temperament attributes
      in early childhood.
AB  - The present study was conducted to examine the contributions of early appearing
      temperament attributes to toddler and preschool-age behavior problems. High
      levels of negative emotionality and low levels of effortful control were linked
      to both externalizing and internalizing difficulties. All fine-grained dimensions
      of negative affect were concurrently associated with internalizing problems
      whereas relations between components of negative affect and externalizing were
      observed only for frustration, sadness, and low falling reactivity. Higher
      surgency was associated with increased risk for externalizing behaviors whereas
      low surgency increased the likelihood of internalizing problems. Trait-by-trait
      moderation occurred, such that negative emotionality was most closely related to
      behavior problems when orienting/regulatory capacity or effortful control was low
      or when infant surgency was high. Results of this study have implications for
      theory linking temperament and psychopathology, and clinical applications
      utilizing temperament assessment to prevent behavior problems.

PMID- 28520103
TI  - Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular
      carcinoma progression.
AB  - : Noncoding RNAs play important roles in cancer biology, providing potential
      targets for cancer intervention. As a new class of endogenous noncoding RNAs,
      circular RNAs (circRNAs) have been recently identified in cell development and
      function, and certain types of pathological responses, generally acting as a
      microRNA (miRNA) sponge to regulate gene expression. Identifying the deregulated
      circRNAs and their roles in cancer has attracted much attention. However, the
      expression profile and function of circRNAs in human hepatocellular carcinoma
      (HCC) remain to be investigated. Here, we analyzed the expression profile of
      human circRNAs in HCC tissues and identified circMTO1 (mitochondrial translation
      optimization 1 homologue; hsa_circRNA_0007874/hsa_circRNA_104135) as one circRNA
      significantly down-regulated in HCC tissues. HCC patients with low circMTO1
      expression had shortened survival. By using a biotin-labeled circMTO1 probe to
      perform RNA in vivo precipitation in HCC cells, we identified miR-9 as the
      circMTO1-associated miRNA. Furthermore, silencing of circMTO1 in HCC could down
      regulate p21, the target of oncogenic miR-9, resulting in the promotion of HCC
      cell proliferation and invasion. In addition, the tumor-promoting effect of
      circMTO1 silencing was blocked by miR9 inhibitor. Intratumoral administration of
      cholesterol-conjugated circMTO1 small interfering RNA promoted tumor growth in
      HCC-bearing mice in vivo. CONCLUSION: circMTO1 suppresses HCC progression by
      acting as the sponge of oncogenic miR-9 to promote p21 expression, suggesting
      that circMTO1 is a potential target in HCC treatment. The decrease of circMTO1 in
      HCC tissues may serve as a prognosis predictor for poor survival of patients.
      (Hepatology 2017;66:1151-1164).

PMID- 28520104
TI  - Use of time and adolescent health-related quality of life/well-being: a scoping
      review.
AB  - : Time use could profoundly affect adolescents' health-related quality of life
      (HRQL). Ideally, overall time use patterns would be considered, because
      activities within a 24-hour day are inherently correlated (more in one activity
      means less in another). This review focused on the associations of (i) overall
      time use patterns and (ii) components of time use patterns with HRQL in
      adolescents. CONCLUSION: More physical activity, less screen time and
      more/adequate sleep, in isolation, are associated with better profile-based HRQL
      subscales. Greater understanding of adolescents' overall time use patterns and
      HRQL is, therefore, a priority for policy development.

PMID- 28520105
TI  - Large-scale computational models of liver metabolism: How far from the clinics?
AB  - Understanding the dynamics of human liver metabolism is fundamental for effective
      diagnosis and treatment of liver diseases. This knowledge can be obtained with
      systems biology/medicine approaches that account for the complexity of hepatic
      responses and their systemic consequences in other organs. Computational modeling
      can reveal hidden principles of the system by classification of individual
      components, analyzing their interactions and simulating the effects that are
      difficult to investigate experimentally. Herein, we review the state-of-the-art
      computational models that describe liver dynamics from metabolic, gene
      regulatory, and signal transduction perspectives. We focus especially on large
      scale liver models described either by genome scale metabolic networks or an
      object-oriented approach. We also discuss the benefits and limitations of each
      modeling approach and their value for clinical applications in diagnosis,
      therapy, and prevention of liver diseases as well as precision medicine in
      hepatology. (Hepatology 2017;66:1323-1334).

PMID- 28520106
TI  - Prophylactic sustained inflation is just one step to preventing bronchopulmonary
      dysplasia.

PMID- 28520107
TI  - Nine-month-olds' triangular interactive strategies with their parents' couple in
      low-coordination families: A descriptive study.
AB  - Observing infants in triadic situations has revealed their triangular competence;
      namely, their ability to interact with both parents by simultaneously sharing
      their attention and affects with them. Infants' triangular interaction is linked
      with the coparenting unit's degree of coordination; in high-coordination (HC)
      families, parents act as a team in relation to the child, thus drawing clear and
      flexible boundaries with them; in low-coordination (LC) families, parents either
      avoid direct interaction with each other and include the child in their unit or
      join together against the child and exclude him or her, thus drawing inconsistent
      boundaries with the child. We explored the interactive strategies of LC 9-month
      olds (n = 15) with those of their parents, comparing them with HC parents (n =
      23) in two conditions: playing with both parents at the same time and witnessing
      their parents' dialogue. LC infants' affects were less positive; they addressed
      fewer positive triangular bids to their parents and tended to use a less
      triangular interactive mode. Thus, LC infants had fewer opportunities than did HC
      infants to acquire skills necessary for coping with triangular interaction.

PMID- 28520109
TI  - Children's emotional responsiveness and sociomoral understanding and associations
      with mothers' and fathers' socialization practices.
AB  - Sixty-two preschoolers (55% boys) were presented hypothetical dilemmas about
      moral transgressions. Responses were evaluated in terms of children's emotional
      responsiveness, prosocial motives, and readiness to intervene. Mothers and
      fathers reported separately on their use of victim-oriented inductions, teaching
      reparations, power assertion, and love withdrawal. Four years later, parents
      reported on children's behavioral problems, emotion-regulation ability, and
      empathy. Mothers reported using more victim-oriented inductions than did fathers,
      and girls responded with more personal distress and reported more rule-oriented
      motives. Maternal love withdrawal was a positive predictor of empathy and motives
      of concern. For fathers, teaching reparations were positively related to
      children's sympathy. Interestingly, mothers' power assertion was negatively
      related to sympathy at high levels of fathers' power assertion, but not at low
      levels. Maternal power assertion during the preschool years was negatively
      associated with children's long-term empathy scores. School-age outcomes also
      were meaningfully predicted by earlier sociomoral competence.

PMID- 28520110
TI  - Behavior problems in young children from low-income families: The development of
      a new screening tool.
AB  - The purpose of this study was to construct a screening tool, the Early Childhood
      Behavior Screen (ECBS), to identify behavior problems and prosocial behaviors in
      very young children (1-5 years old) from low-income backgrounds. Field testing of
      the initial screening tool was conducted with a representative, diverse sample of
      439 parents from a low-income, urban community. The final 20-item scale was
      written at a 3.9 grade reading level. Psychometric properties of the ECBS
      revealed that the items loaded on two factors, the Challenging Behavior factor
      and the Prosocial Behavior factor. Each factor demonstrated high levels of
      internal consistency (.87 and .92, respectively). The Challenging Behavior factor
      demonstrated adequate levels of concurrent validity (r = .75), sensitivity (r =
      .82), and specificity (r = .80) based on its relationship with the Eyberg Child
      Behavior Inventory (S.M. Eyberg & D. Pincus, 1999). The Prosocial Behavior factor
      is a clinically useful aspect of the ECBS, as it allows researchers and
      practitioners to identify the child's positive behaviors as part of a strength
      based approach to treatment. The results suggested that the ECBS has potential as
      a brief screening tool that is useful in pediatric, psychological, and
      educational settings that serve low-income populations to aid in the
      identification of young children with challenging behaviors that may require
      intervention services.

PMID- 28520111
TI  - The good, the bad, and the ambivalent: Quality of alliance in a support program
      for young mothers.
AB  - The relationship that develops between early childhood service providers and
      parents is seen as a critical component in program implementation, although
      little is known about how service providers and parents view this relationship.
      The current qualitative study examines the helping relationship between doulas
      and 12 African American adolescent mothers who participated in a larger study of
      prenatal and postnatal support. Mothers and their doulas were interviewed
      separately at the beginning and the end of program participation about the
      quality of the helping relationship and how they spent their time together.
      Content analysis revealed positive, negative, and ambivalent themes in mothers'
      and doulas' descriptions of their relationships, although the majority of the
      relationships were considered positive. For the most part, doulas and mothers
      agreed on the quality of the relationship that they formed with each other.
      Mothers were more likely to note the enjoyable aspects of spending time with
      their doula while doulas focused more on issues of trust and acceptance. The
      young mothers and doulas often considered amount of contact and availability (or
      lack thereof) as a sign of the quality of the relationship. Results are discussed
      in terms of the professional role of the doula and cultural influences in help
      giving behavior.

PMID- 28520112
TI  - Proapoptotic signaling induced by deletion of receptor-interacting kinase 1 and
      TNF receptor-associated factor 2 results in liver carcinogenesis.

PMID- 28520115
TI  - Emotional Expression and Language: A Longitudinal Study of Typically Developing
      Earlier and Later Talkers from 15 to 30 Months.

PMID- 28520113
TI  - Coparenting interactions observed by the prenatal lausanne trilogue play: An
      Italian replication study.
AB  - The infant-parent interaction is the focus of interest on early interactive
      relational models in the triadic perspective. This approach considers the mother
      father-child interaction as the matrix of early competences, which start to
      develop well before delivery. This theoretical approach has generated an
      observation paradigm, the Lausanne Trilogue Play (LTP; E. Fivaz-Depeursinge & A.
      Corboz-Warnery, 1999). The aim of the study was to investigate (a) the
      psychometric characteristics of coding of the prenatal LTP procedure and their
      comparison with the Lausanne validation studies and (b) the characteristics of
      triadic interactions during pregnancy. Ninety-eight nonreferred, primiparous
      families were recruited at childbirth courses. In addition to validated
      questionnaires, observational data were collected at the seventh month of
      pregnancy in the prenatal LTP. The collected data show good reliability of the
      LTP coding and a consistent factorial structure in line with the Lausanne
      validation studies (C. Carneiro, A. Corboz-Warnery, & E. Fivaz-Depeursinge, 2006;
      N. Favez et al., 2006). The Structure of the Play and the Intuitive Parenting
      Behaviors Scales seem the most representative dimensions in the prenatal period.
      Coparental abilities during pregnancy represent an interactive matrix for the
      construction of early family relations and may be considered as protective
      factors in the child's development of early triadic interactive abilities.

PMID- 28520116
TI  - Emotional Expression and Language: A Psycholinguistic Perspective: Commentary to
      Kubicek & Emde, Emotional Expression and Language: A Longitudinal Study of
      Typically Developing Earlier and Later Talkers from 15 to 30 Months.

PMID- 28520117
TI  - From the Start: Integration of Affect and Language in Parent-Infant Interactions:
      Commentary to Kubicek and EMDE, Emotional Expression and Language: A Longitudinal
      Study of Typically Developing Earlier and Later Talkers from 15 to 30 Months.

PMID- 28520118
TI  - Reflective family play: A model for whole family intervention in the infant and
      preschool clinical population.
AB  - This article proposes a new treatment model, Reflective Family Play, for clinical
      intervention in two-parent families of children aged 0 to 5 years. It is play
      based and grounded in the evidence-based treatment approach of Watch Wait and
      Wonder (WWW) as well as the assessment tool known as the Lausanne Family Play
      paradigm (LFP). WWW is a dyadic treatment for caregivers and their infants or
      preschoolers that has been shown to shift attachment in the very young (N.J.
      Cohen, E. Muir, & M. Lojkasek, 1999; N.J. Cohen, M. Lojkasek, E. Muir, R. Muir &
      C.J. Parker, 2002). The LFP is a more recent adaptation of the Lausanne Trilogue
      Play paradigm (LTP; E. Fivaz-Depeursinge & A. Corboz-Warnery, 1999). Together,
      the LTP/LFP have now been used for over 2 decades as reliable measures of the
      family alliance and interactions in two-parent households. By combining concepts
      from WWW and the LTP/LFP, a novel approach is presented for treatment in two
      caregiver households. Clinical excerpts are used to illustrate.

PMID- 28520119
TI  - Emotional Expression and Language: A Longitudinal Study of Typically Developing
      Earlier and Later Talkers from 15 to 30 Months.
AB  - Children's emotional expression and language both develop during infancy and
      early childhood, yet these two communication systems have been studied primarily
      in isolation. This study focuses instead on assessing the relation between them
      just as productive language emerges during toddlerhood. Seventy-seven typically
      developing, firstborn toddlers and their families were recruited at 13 months of
      age. Using an extreme groups design, earlier and later talkers were selected
      based on their MacArthur Communicative Development Inventory production scores.
      Laboratory visits occurred at 15, 21, and 30 months; home visits occurred at 3
      month intervals from 15 to 30 months. Observational and parent report measures
      assessed child language, emotional expression, temperament, and overall
      developmental functioning. Parents also reported on parenting stress and family
      life events. Overall, results support a significant relation between emotional
      expression and productive language that varies according to the specific emotion,
      a finding that may resolve earlier contradictory results in this area. Earlier
      talkers expressed more joy/pleasure than did later talkers, but later talkers
      expressed more fear and anger than did earlier talkers. Potential contributions
      of various child/family factors were explored. Child temperament is proposed as
      influencing this relation through its effects on the child's transactions with
      the caregiving environment.

PMID- 28520120
TI  - The Relationship between Temperamental Negative Affect, Effortful Control, and
      Sensory Regulation: A New Look.
AB  - Temperamental negative affectivity (NA) and effortful control (EC) have long been
      of interest to psychologists, but sensory regulation (SR) has received less
      attention. Using confirmatory factor analysis, the present study reexamined the
      Rothbart model of EC and NA using the Children's Behavior Questionnaire (CBQ;
      M.K. Rothbart, S.A. Ahadi, K.L. Hershy, & P. Fisher, 2001), along with
      alternative models of EC, NA, and SR using the CBQ and Short Sensory Profile. The
      results failed to replicate the Rothbart model of EC and NA, which includes SR
      within the EC and NA factors. A good fit was found for a three-factor model (EC,
      NA, and SR) that was replicated in a holdout sample. A three-factor model also
      showed a good fit when EC, NA, and SR items similar to symptoms of behavior
      problems were eliminated.

PMID- 28520122
TI  - A Study of Emotional Expression and Language: Implications for Studying and
      Understanding Development of Emotions: Commentary to Kubicek and Emde, Emotional
      Expression and Language: A Longitudinal Study of Typically Developing Earlier and
      Later Talkers from 15 to 30 Months.

PMID- 28520123
TI  - Getting Ready: Results of a Randomized Trial of a Relationship-Focused
      Intervention on the Parent-Infant Relationship in Rural Early Head Start.

PMID- 28520124
TI  - Report on the natural interruption of pregnancy related to menarche in the
      population of Madrid.
AB  - All cases of spontaneous abortion which were registered between June 1982 and
      June 1984 in the Ciudad Sanitaria de la Paz have been studied in Madrid (n =
      1,259). Together with the women who had miscarriages, a control sample of women
      (n = 1,016) of similar socioeconomic status and ages was analyzed. The main aim
      of this study is the analysis of the link between the age of menarche and the
      incidence of miscarriage, as well as morphological characteristics of women. Our
      results demonstrate that the average age of menarche is earlier in the sample of
      women who have a miscarriage (P > .001). When women are classified by early,
      middle, or late age at menarche, it was observed that, for the sample of women
      who had a miscarriage, there is a higher percentage of both early and late age at
      menarche. No significant differences were found in the rest of the morphological
      variables which were considered. The cycles of women who had miscarriages were
      more irregular than those in the control group.

PMID- 28520125
TI  - Contributions of nutrition versus hypoxia to growth in rural Andean populations.
AB  - Previous research on diet and nutrition among peasant agriculturalists in the
      Andes has produced inconsistent results. As a consequence it has been difficult
      to determine the extent to which nutritional factors contribute to the slowed,
      prolonged growth and resultant small adult body size that is characteristic of
      these highland populations. The study examines patterns of diet and growth in the
      rural highland community of Nunoa, Peru (elevation 4,000 m), and compares them to
      similar data collected on this community during the 1960s. Additional data from
      other locations in the Andes are then evaluated to discern critical determinants
      of growth variation. Analyses of the Nunoan data indicate that nutritional
      factors have played a significant role in shaping statural growth at this
      location. Comparisons of other growth surveys indicate that Nunoans remain among
      the smallest of all Andean populations. Additionally, urban/rural differences in
      growth are quite evident in the highlands, with the magnitude of this difference
      being greater than in other regions (i.e., coastal or jungle). It appears that
      income level and access to land strongly interact to direct and constrain food
      consumption patterns. The resulting differences in nutrition, in turn, appear to
      be strong predictors of growth variation. Consequently, studies that consider 1)
      dietary intake, 2) level of variability in diet, and 3) relative contributions of
      purchased and home-produced food to diet should contribute to furthering our
      understanding of growth variation in the Andes.

PMID- 28520126
TI  - Mortality among Serere children in Senegal.
AB  - Seasonal variation in nutritional status and child survival was studied in a
      representative sample of 40 Serere households in a rural area in Senegal. Hazard
      models (Gage: Am. J. Phys. Anthropol. 76: 429-441, 1988, Rosenberg: J. Biosoc.
      Sci. 21(3): 335-348, 1989) were used to investigate risk factors associated with
      child mortality in a Senegalese rural area. Not surprisingly the most important
      risk factor was the child's nutritional status, as reflected in the BMI. These
      models can incorporate sequentially observed information and in this way it
      becomes clear how a falling relative BMI manifested itself in a sharply rising
      hazard rate. In addition to the BMI, we investigated other risk factors and their
      relation to child survival. Of these, birth rank and mother's age were seen to be
      associated with survival and all the more so in the presence of an unfavourably
      evolving BMI.

PMID- 28520127
TI  - Increased diffusion capacity maintains arterial saturation during exercise in the
      Quechua Indians of Chilean Altiplano.

PMID- 28520128
TI  - Birth seasonality in a Rural U.S. county, 1911-1979.
AB  - This paper examines birth seasonality in a rural U.S. county over the period 1911
      1979. Data were taken from the complete series of birth certificates for the
      county population during this period. Birth seasonality was expected to reflect
      seasonal variation in agricultural workload earlier in the century (pre-1940) but
      to disappear as this population became more integrated into the wage labor market
      from 1940 to 1979. The pattern of birth seasonality in each decade from the 1910s
      to the 1970s by week, month, and season was analyzed with descriptive and
      analytic techniques. However, no birth seasonality was found for any decade
      during this century. The absence of a seasonal fertility pattern remained when
      all births were examined, and when such factors as ethnicity (only births to
      white mothers), occupation (only births to women married to farmers), and
      stillbirths were controlled singly and in combination. The implications of the
      lack of birth seasonality in this population are discussed in terms of the
      understanding of the causes of birth seasonality and the place of birth
      seasonality in human adaptation.

PMID- 28520129
TI  - Developmental responses to high-altitude hypoxia in Bolivian children of European
      ancestry: A test of the developmental adaptation hypothesis.
AB  - The developmental adaptation hypothesis (DAH) proposes that highlanders adapt to
      their hypobaric hypoxic environment during growth and development. This report
      utilizes data on children (9.0-19.9 yr) of European ancestry residing in Santa
      Cruz and La Paz, Bolivia, to test selected aspects of the DAH. Previous tests of
      this hypothesis have been hampered by difficulties in controlling for
      socioeconomic and genetic influences. However, due to their high socioeconomic
      status and their relatively short history of residence at high altitudes, these
      factors can be reasonably well controlled in studies of European children. The
      data on European children are consistent with some but not all aspects of the
      DAH. First, examination of the available data on VO2 max (ml/kg/min) in European
      boys suggests that chronic exposure to hypobaric hypoxia results in an
      enhancement of the overall functional capacity of the oxygen transport system
      during adolescence, as predicted by the DAH. Second, chronic exposure to
      hypobaric hypoxia results in a delay in linear growth and maturation in European
      children, as well as in an enhancement of their lung volumes, also as predicted
      by the DAH. However, the effects of chronic hypoxia on linear growth, after
      controlling for health and nutritional status, are not as large as previously
      believed and, contrary to the expectations of the DAH, they need not be acquired
      through a distinctive pattern of growth during late childhood and adolescence.
      Instead, it appears that these patterns are established in European highlanders
      prior to 9 years of age and are then maintained, rather than accentuated, during
      later developmental periods.

PMID- 28520130
TI  - Birth order effects on dermatoglyphs on fingers, palms, toes, and soles.
AB  - Coefficients of correlation of 47 dermatoglyphic traits with birth order vary
      widely in a sample of 145 sibships of a Bengali speaking population. In general,
      ridge-counts and pattern intensities tend to decrease with birth order. Linear
      effects of birth order are, however, significant in samples of two sexes only for
      ridge-counts on the ab regions of palms and on toes, and in males only for
      triradial number on toes, D-line exit, hallucal ridge-count and triradial number
      on soles, and ridge-count on index fingers. Their relative intensities do not
      follow the order of appearance or of heritabilites of the traits. The maximal atd
      angle, which has a negligible correlation with birth order, shows no consistent
      trend of a linear or non-linear change with birth order in the two sexes even
      within sibships.

PMID- 28520131
TI  - Ventilation and the control of erythropoiesis in high-altitude natives of Chile
      and Nepal.

PMID- 28520132
TI  - Epilogue.

PMID- 28520133
TI  - Introduction.
AB  - A basic premise of studies conducted in the 1950s and 1960s was that humans
      exhibited a uniform set of biological responses to the high altitude environment.
      Since then, investigations have been carried out in the North American Rockies,
      South American Andes, and the Himalayas by researchers from a variety of
      disciplines-biological anthropology, respiratory physiology, cardiology,
      hematology, and nutrition. These studies have contributed important insights for
      understanding the mechanisms involved in adaptation to high altitude and have
      revealed possible differences in the strategies of adaptation exhibited by the
      world's various high altitude populations. However, the findings have sometimes
      been slow to percolate across disciplinary boundaries, given the tradition among
      the biological sciences to conduct research and present findings in specialized
      groupings. This symposium breaks this pattern by bringing together from several
      disciplines investigators who are actively involved in the conduct of high
      altitude studies. The interaction afforded enables us to realize that
      understanding the process of human adaptation to high altitude requires a
      holistic approach whereby the expertise of various scientific disciplines needs
      to be utilized in a synchronized and integrated manner.

PMID- 28520134
TI  - Estimation of total body composition by regional dual photon absorptiometry.
AB  - The accuracy of estimating total body composition from dual photon absorptiometry
      (DPA) and the soft tissue attenuation ratio (Rst) from regional scans over the
      abdomen was investigated in a group (n = 82) of young adult (age = 17-38 years)
      females with diverse activity histories. Forearm bone mineral content (BMC) was
      estimated from single photon absorptiometry. Lumbar vertebrae and femur BMC, and
      trunk (lumbar region) soft tissue composition (Rst) were estimated from DPA.
      Percent body fat, the criterion variable, was estimated from body density (BD)
      after adjusting for individual variation in BMC, an important source of
      variability in body density. The test-retest reliability of Rst, assessed in a
      second group of subjects (n = 30), was excellent (r = 0.99; SEM = 0.10%). Rst was
      significantly (P <= .05) correlated with body density (r = .78), limb and
      especially trunk skinfolds, and predicted total body fat (%) with an SEE of 3.9%.
      These results demonstrate that DPA is a useful technique for obtaining estimates
      of both bone mineral and soft tissue composition, particularly in populations
      suspected to have significant bone loss. Given the association between Rst and
      trunk (abdominal) fat, DPA may prove to be a useful technique for investigating
      the association between abdominal fat and disease.

PMID- 28520135
TI  - Variation in hemoglobin concentration among samples of high-altitude natives in
      the Andes and the Himalayas.
AB  - This paper presents data on hemoglobin concentration in a rural Andean sample at
      3,800-3,900 m and incorporates them into a review intended to evaluate possible
      sources of the range of variation in mean hemoglobin concentration among samples
      obtained at high altitude. Between 3,400 and 4,000 m, rural Himalayan highlanders
      average 1.4 gm/dl lower mean hemoglobin concentration than rural Andean
      highlanders. With respect to potential causes of anemia, it is concluded that the
      relatively low values of rural Himalyan populations are not explicable by lower
      hypoxic stress or different techniques of obtaining and analyzing blood samples
      and are probably not explicable by nutritional deficiency and disease. With
      respect to potential causes of polycythemia within Andean populations, it is
      concluded that the somewhat higher values of some mining and urban samples of
      Andean higlanders may not be due to the mining occupation per se but may be due
      partly to the inclusion of European and mestizo (with at most 500 years of high
      altitude ancestry) along with Amerindian highlanders (with millenia of high
      altitude ancestry) as well as to the inclusion of highlanders living well above
      their own habitual altitudes of residence. The Andean polycythemia is probably
      not due to obesity, high androgen levels, or frequent intermittent hypoxemia
      during sleep. The effect of heavy smoking cannot be evaluated. Further work on
      hematological adaptation to high altitude must pay special attention to sample
      characteristics.

PMID- 28520136
TI  - Editorial.

PMID- 28520137
TI  - Ethnic variation in the size of infant at birth.
AB  - The impact of ethnicity and other maternal factors (BMI, parity, glucose
      tolerance, gestational age) on the size of the infant at birth was investigated
      in a relatively low socioeconomic status, multi-ethnic population at San
      Francisco General Hospital. A sample of 2,069 infants born to mothers of black,
      non-Hispanic white, Hispanic, and Chinese descent and whose mothers had received
      prenatal care at San Francisco General Hospital were studied. Maternal size,
      pregnancy history, and blood glucose were determined prenatally at 26-28 weeks
      gestation. Anthropometry was performed on the infant within 72 hours of birth.
      Black and Chinese infants were the lightest in weight, while Hispanic infants
      were the heaviest. When correction was made for maternal factors black infants
      were shown to be significantly (P < .05) lighter in birth weight than non
      Hispanic white, Chinese, or Hispanic infants. Black infants were also
      significantly shorter in birth length and smaller in chest circumference. Chinese
      infants had significantly (P < .05) greater adiposity, as indicated by the sum of
      skinfold measurements, than both black and Hispanic infants. These findings are
      relevant to current practices in neonatal growth categories which are determined
      solely by birth weight and do not account for variations in body composition.
      Comparisons with a relatively higher socioeconomic status sample from Kaiser
      Permanente Hospital (Oakland) shows a similar prevalence of low birth weight
      among blacks. These results support other results that ethnicity is a major
      independent influence on the weight of the newborn.

PMID- 28520138
TI  - Maternal O2 transport and fetal growth in Colorado, Peru, and Tibet high-altitude
      residents.
AB  - Human populations have lived at high altitudes for lengths of time which are
      likely to be shortest in Colorado, intermediate in Peru, and longest in Tibet. We
      hypothesized that the longest-resident high-altitude populations have beccome
      better adapted than shorter-resident groups as a result of superior abilities to
      transport and/or utilize O2 . Because birth weights are reduced at high altitude
      and decreased birth weight is associated with increased infant mortality, our
      criterion for assessing adaptation was preservation of birth weights close to
      values associated with the lowest mortality risk. Colorado (3,100 m) and Peru
      (4,300 m) birth weights averaged 3,186+/-70 g and 2,920+/-90 g respectively. A
      sample of 15 births from Tibet (3,658 m) weighed 3,307+/-110 g which was more
      than their altitude counterparts and close to sea-level norms. Pregnancy
      increased maternal ventilation at all three study sites. In Peru, the resultant
      elevation in arterial O2 saturation offset the pregnancy-induced fall in
      hemoglobin concentration to preserve arterial O2 content at nonpregnant levels.
      Arterial O2 content decreased slightly in Colorado and more markedly in Tibet in
      the pregnant compared to the nonpregnant state. The Colorado and Peru women with
      the greatest rise in ventilation and ventilatory sensitivity to hypoxia produced
      the heaviest birthweight infants, suggesting that maternal arterial oxygenation
      was an important determinant of fetal growth. The pregnant women in Tibet did not
      have higher levels of arterial O2 content than the pregnant Colorado or Peru
      women nor did maternal arterial O2 content relate to birth weight in Tibet.
      Infant birth weight in Tibet tended to be correlated with the ratio of uterine
      artery to common iliac artery mean flow velocity, suggesting that redistribution
      of lower-extremity blood flow to favor the uterine circulation may have acted to
      augment uterine O2 delivery in the Tibet women. Thus, the limited data available
      suggested that the Tibetans may be better adapted as judged by less fetal growth
      retardation and may utilize maternal O2 transport mechanisms not reliant upon
      increased arterial O2 content.

PMID- 28520139
TI  - Applications of anthropometry to epidemiologic studies of nutrition and cancer.
AB  - Epidemiologic research on cancer has recently expanded into new areas of
      investigation directly related to aspects of human biology, such as human diet
      and nutrition. The overall pattern of scientific evidence has suggested that
      dietary patterns in early life, as well as in adulthood, may be related to the
      long-term risk of certain cancers. Anthropometry has considerable potential in
      cancer research as an indirect means of both childhood and adult nutritional
      assessment. Anthropometry has advantages in application to cancer studies when
      the sample size is large, as it must be to test most contemporary diet-cancer
      hypotheses. The anthropometric dimensions selected for measurement should be
      reliable, readily accessible in field or clinical situations with high rates of
      subject participation, have established correlations to other body dimensions,
      and be comparable to dimensions measured in other studies. Appropriate standards
      of practice and quality control procedures in cancer studies may differ somewhat
      from those employed in human growth studies. Anthropometry is an important
      biomedical research methodology, which may be used to study the relations between
      nutrition, body size, and cancer, leading to better identification of individuals
      and human populations at increased risk.

PMID- 28520141
TI  - Quality of attachment, perinatal risk, and mother-infant interaction in a high
      risk premature sample.
AB  - Thirty-three families, each with a premature infant born less than 33 gestational
      weeks, were observed in a longitudinal exploratory study. Infants were recruited
      in a neonatal intensive care unit, and follow-up visits took place at 4 months
      and 12 months of corrected age. The severity of the perinatal problems was
      evaluated using the Perinatal Risk Inventory (PERI; A.P. Scheiner & M.E. Sexton,
      1991). At 4 months, mother-infant play interaction was observed and coded
      according to the CARE-index (P.M. Crittenden, 2003); at 12 months, the Strange
      Situation Procedure (SSP; M.D.S. Ainsworth, M.C. Blehar, E. Waters, & S. Wall,
      1978) was administered. Results indicate a strong correlation between the
      severity of perinatal problems and the quality of attachment at 12 months. Based
      on the PERI, infants with high medical risks more frequently tended to be
      insecurely attached. There also was a significant correlation between insecure
      attachment and dyadic play interaction at 4 months (i.e., maternal controlling
      behavior and infant compulsive compliance). Moreover, specific dyadic interactive
      patterns could be identified as protective or as risk factors regarding the
      quality of attachment. Considering that attachment may have long-term influence
      on child development, these results underline the need for particular attention
      to risk factors regarding attachment among premature infants.

PMID- 28520142
TI  - Which preventive interventions effectively enhance depressed mothers'
      sensitivity? A meta-analysis.
AB  - Improving depressed mothers' sensitivity is assumed to be a key element in
      preventing adverse outcomes for children of such mothers. This meta-analysis
      examines the short-term effectiveness of preventive interventions in terms of
      enhancing depressed mothers' sensitivity toward their child and investigates what
      type of intervention is most effective. Thirteen interventions, reported in 10
      controlled outcome studies, met the inclusion criteria (N = 918). Meta-analytic
      results showed a small to medium, significant mean effect size (g = 0.32) with
      large variation in individual effect sizes (-0.56-1.76). Interventions including
      baby massage were highly effective in improving maternal sensitivity (g = 0.85).
      In contrast, individual therapy for the mother proved ineffective in terms of
      improving maternal sensitivity (g = -0.00). Two other significant predictors of
      greater effect sizes were the inclusion of a support group and the use of a
      higher number of intervention methods; however, the significance of these results
      was largely accounted for by one single study. Our meta-analysis confirms that
      depressed mothers' sensitivity can be improved by preventive intervention and
      suggests that baby massage may be an effective intervention method to evoke short
      term changes in maternal sensitivity. It is unclear whether these changes are
      maintained over time.

PMID- 28520140
TI  - Identification of Breast Cancer Inhibitors Specific for G Protein-Coupled
      Estrogen Receptor (GPER)-Expressing Cells.
AB  - Together with estrogen receptors ERalpha and ERbeta, the G protein-coupled
      estrogen receptor (GPER) mediates important pathophysiological signaling pathways
      induced by estrogens and is currently regarded as a promising target for ER
      negative (ER-) and triple-negative (TN) breast cancer. Only a few selective GPER
      modulators have been reported to date, and their use in cancer cell lines has
      often led to contradictory results. Herein we report the application of virtual
      screening and cell-based studies for the identification of new chemical scaffolds
      with a specific antiproliferative effect against GPER-expressing breast cancer
      cell lines. Out of the four different scaffolds identified, 8-chloro-4-(4
      chlorophenyl)pyrrolo[1,2-a]quinoxaline 14 c was found to be the most promising
      compound able to induce: 1) antiproliferative activity in GPER-expressing cell
      lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not
      express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained
      induction of cell-cycle negative regulators p53 and p21.

PMID- 28520143
TI  - Exploration of the links among fathers' unresolved states of mind with respect to
      attachment, atypical paternal behavior, and disorganized infant-father
      attachment.
AB  - Atypical maternal behavior has consistently been identified as a precursor of
      disorganized infant-mother attachment, but to date, no research has examined the
      role of atypical paternal behavior in the development of disorganized infant
      father attachment. This study aims to enhance our understanding and
      conceptualization of infant-father attachment by examining the role of fathers'
      unresolved states of mind and the display of atypical paternal behavior in the
      development of disorganized infant-father attachment. Thirty-one middle-class
      couples participated in this study. Maternal and paternal Adult Attachment
      Interviews (C. George, N. Kaplan, & M. Main, 1996) were completed prenatally and
      at infant age 6 months, respectively. Infant-mother and infant-father dyads
      participated in the Strange Situation paradigm (M. Ainsworth, M. Blehar, E.
      Waters, & S. Wall, 1978) when the infants were 12 and 18 months of age,
      respectively. The Atypical Maternal Behavior Instrument for Assessment and
      Classification (E. Bronfman, E. Parsons, & K. Lyons-Ruth, 1999) was used to
      assess maternal and paternal behavior during the Strange Situation. Maternal
      states of mind regarding attachment predicted infant-mother attachment
      relationships, and paternal states of mind predicted infant-father attachment
      relationships. Atypical maternal behavior was associated with infant-mother
      disorganized attachment; however, atypical paternal behavior did not predict
      infant-father disorganized attachment. Thus, it is possible that other factors,
      yet to be uncovered, might contribute to the development of infant-father
      disorganized attachment.

PMID- 28520144
TI  - Deconstructing antenatal depression: What is it that matters for neonatal
      behavioral functioning?
AB  - This prospective study examined the variability within clinical characteristics
      of antenatal maternal depression and cortisol levels for associations with
      newborn infant behavior using the Neonatal Behavioral Assessment Scale (NBAS;
      T.B. Brazelton, 1984). Participants were 81 pregnant women at risk for perinatal
      depression given their histories of depression prior to pregnancy. We took into
      consideration not only whether the woman experienced antenatal depression but
      also whether the depression met diagnostic criteria and variability in timing
      (onset and occurrence) of antenatal depression and symptom severity. Infants of
      mothers who became depressed during pregnancy scored less optimally on a subset
      of the NBAS scales, specifically those scales related to infant neuroregulation.
      Among the clinical characteristics of depression, the fetus' overall exposure to
      mothers' depression (reflected in the mean) was most often and most strongly
      associated with NBAS scales. In terms of timing, third-trimester exposure was
      significantly related to newborn behavior. The findings are discussed within the
      S.H. Goodman and I.H. Gotlib (1999) model for transmission of psychopathology to
      offspring of depressed mothers.

PMID- 28520145
TI  - Evaluating a home-based dyadic intervention: Changes in postpartum depression,
      maternal perceptions, and mother-infant interactions.
AB  - Psychotherapeutic treatments that focus on improving the relational processes
      between mothers with postpartum depression (PPD) and their infants, as well as
      the mother's individual therapeutic needs, have a great potential to positively
      impact the mother, her infant, and their relationship (K.J. Nylen, T.E. Moran,
      C.L. Franklin, & M. O'Hara, 2006). Utilizing pilot data from an evaluation of a
      home-based dyadic therapy for mothers with PPD and their infants, this article
      reports on a recent academic-community partnership study. The effectiveness of
      the intervention was examined, specifically regarding changes in mother's mood,
      parenting experience, and relationship with her infant. In addition, associations
      were examined among maternal self-report variables measuring change from pre- to
      posttreatment in PPD, psychological distress, and maternal perceptions of
      parenting and those variables measuring change in observer ratings of maternal
      infant interactions. Results showed improvements in mothers' depression,
      distress, and perceptions of parenting as well as many ratings of mothers'
      interactions with their infants. However, only improvements in maternal
      perceptions of parenting, such as maternal self-esteem and parenting stress, were
      associated with better mother--infant interactions. Importance of this research
      for the field of infant mental health as well as clinical implications are
      discussed.

PMID- 28520147
TI  - Toward a method for analyzing series of clinical cases.
AB  - This article describes the development of this special issue, and emphasizes the
      need for a methodology to gather and summarize clinical experience and meta
      analyze clinical cases.

PMID- 28520146
TI  - Association of tenofovir disoproxil fumarate with primary allograft survival in
      HIV-positive kidney transplant recipients.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is an antiretroviral agent
      frequently used to treat human immunodeficiency virus (HIV). There are concerns
      regarding its potential to cause acute kidney injury, chronic kidney disease, and
      proximal tubulopathy. Although TDF can effectively suppress HIV after kidney
      transplantation, it is unknown whether use of TDF-based antiretroviral therapy
      (ART) after kidney transplantation adversely affects allograft survival. METHODS:
      We examined 104 HIV+ kidney transplant (KT) recipients at our center between 2001
      and 2014. We generated a propensity score for TDF treatment using recipient and
      donor characteristics. We then fit Cox proportional hazards models to investigate
      the association between TDF treatment and 3-year, death-censored primary
      allograft failure, adjusting for the propensity score and delayed graft function
      (DGF). RESULTS: Of the 104 HIV+ KT candidates who underwent transplantation
      during the study period, 23 (22%) were maintained on TDF-based ART at the time of
      transplantation, and 81 (78%) were on non-TDF-based ART. Median age of the cohort
      was 48 years; 87% were male; 88% were black; and median CD4 count at
      transplantation was 450 cells/mm3 . Median kidney donor risk index was 1.2. At 3
      years post transplantation, primary allograft failure occurred in 26% of patients
      on TDF-based ART and in 28% of patients on non-TDF-based ART (P=.5). TDF
      treatment was not associated with primary allograft failure at 3 years post
      transplant after adjusting for DGF and a propensity score for TDF use (hazard
      ratio 2.12, 95% confidence interval 0.41-10.9). CONCLUSIONS: In a large single
      center experience of HIV+ kidney transplantation, TDF use following kidney
      transplantation was not significantly associated with primary allograft failure.
      These results may help inform management for HIV+ KT recipients in need of TDF
      therapy for adequate viral suppression.

PMID- 28520148
TI  - A systems perspective on the integrative child psychiatry approach. Discussion of
      paper: "Working here and now with the individual and family system: A case of a
      traumatized child".
AB  - In this discussion, after a few general comments, I will propose a systems
      reading of the intervention so elegantly described by Kaija Puura. I will draw
      parallels between the therapeutic and the family groups as framing-developing
      systems and formalize the steps taken by the family toward healing under the
      influence of the therapist's team.

PMID- 28520149
TI  - The music of containment: Addressing the participants in mother-infant
      psychoanalytic treatment.
AB  - The author discusses the psychoanalyst's approach in mother-infant treatments.
      Emphasis is given to the infant as an important, though often neglected,
      addressee. A clinical example is used in which a telephone call during a prior
      session triggered fretting in a 3-month-old girl and distress in her mother. It
      is suggested that in the session, nonverbal levels of the interventions reached
      the girl and contained her, and that this containment worked along similar lines
      as the communicative musicality between mother and baby. In the discussion, the
      psychoanalytic concept of containment (Bion, 1962) is linked with the concept of
      communicative musicality (Trevarthen & Aitken, 2001). The mother's need for
      containment also is emphasized, and the therapist must be on alert when it is
      essential to focus on either participant in the therapy room. This choice is
      guided both by explicit deliberations and by the unconscious countertransference.
      However, the therapist's wish to grasp the countertransference is countered by
      his or her unwillingness of being reminded of feelings of infantile helplessness.
      Similarly, when the mother's conscious and unconscious messages diverge, the
      baby's ability to receive her caretaking is compromised. In the article's
      clinical case, this happened when the mother tried to soothe her daughter while
      being preoccupied with anger at the therapist to an extent to which she was not
      fully aware.

PMID- 28520150
TI  - An infant who was born with a life-threatening skin disease: Various aspects of
      triadic psychotherapy.
AB  - A longitudinal case study of a 3-year-old toddler, born with a congenital,
      severe, life-threatening skin disease, with comorbid diagnoses of failure to
      thrive and feeding disorder, is described and discussed. The referral,
      diagnostic, and therapeutic processes are described, and the main themes of the
      treatment sessions are presented in the associative order that they occurred. The
      understanding of the case is very much based on the "me-skin'' concept. We have
      tried, through this case, to show the ways that we work with multidisciplinary
      team countertransferential reactions to the young child and her parents, the role
      that the child psychiatrist may take, and the special difficulty in working with
      cases that raise fear of death in parents as well as in therapists. We raise
      existential questions about worth of life, infant's will to grow, and infant's
      drive to live forever a painful life.

PMID- 28520151
TI  - Working here and now with the individual and family system: A case of a
      traumatized girl.
AB  - From the moment of conception, each and every child lives and develops in
      connection with other people. Most children grow up in families formed by
      parent(s) and siblings, and relationships with them form an important part of the
      environment in which they develop. Interaction with parents and siblings affects
      brain development and the intrapsychic structures of the child. In the last few
      decades, knowledge of both normal and abnormal development of the human brain and
      mind has increased, revealing the complicated interplay of neurophysiology,
      emotions, and behavior within an individual as well as in interaction with
      others. In an attempt to address the challenge of working with various existing
      frameworks, in the Child Psychiatric Department of Tampere University Hospital,
      Professor Tuula Tamminen started a clinical philosophy called integrative child
      psychiatry. It includes looking at a child's situation from different
      perspectives and integrating data gathered into clinical understanding to choose
      the optimal treatment. In this article, I describe how I used individual child
      therapy, family therapeutic methods, psychoeducation, and some simple behavioral
      techniques in the treatment of a sexually abused girl.

PMID- 28520152
TI  - Understanding changes and children. Discussion of paper: "Child analysis in a
      changing world".

PMID- 28520153
TI  - Clinical challenges of adoption: Views from Montreal and Tel Aviv.
AB  - Adoption is accompanied by well-known risk factors that contribute to unique
      clinical challenges for children, parents, and clinicians. Adoption also serves
      to illustrate issues that remain relatively "silent" in the typical transition to
      parenthood. In this article, the authors review the normal developmental
      challenges that parents face during adoption, the adoption-related risk factors
      that may impinge on the child's development and attachment process, and the
      impact of adoption on the child's development of identity and filiations. We will
      review and illustrate clinical conditions often associated with adoption. In many
      countries, adoptive parents are reluctant to consult mental health clinicians
      during the first year of the adoption. The cases presented here illustrates the
      need to implement routine clinical programs for early detection and intervention
      of adoptive parent-infant dyads and triads at risk.

PMID- 28520154
TI  - Adding some notes to the "Music of Containment". Discussion of paper: "The Music
      of Containment: Addressing the participants in mother-infant psychoanalytic
      treatment".
AB  - Thinking about the psychoanalytical process in parent-infant psychotherapy is the
      purpose of Bjorn Salomonsson's article. He proposes to consider that containment
      is the core of the treatment and that musicality is his main vehicle. His thought
      is linked with the research on primary intersubjectivity and is so exciting for
      all the parent-infant therapists. For myself, I emphasize the use of the
      psychoanalytical concept of affects rather than emotions, and I present my
      understanding of the transference phenomena with the part of the infantile
      sexuality of all the participants.

PMID- 28520155
TI  - Final comments.

PMID- 28520156
TI  - The quality of the relationship as a factor of change. Discussion of paper:
      "Challenges working with infants and their families: Symptoms and meanings-two
      approaches of infant-parent psychotherapy".

PMID- 28520157
TI  - Child analysis in a changing world. In the face of a paradigm shift from the mind
      to the brain: Can we meet the challenge?
AB  - Child analysts and child therapists are now practicing in a new environment where
      an increased emphasis is made on identifying the symptoms and finding the
      shortest possible way to get rid of them, from the knowledge of brain
      functioning. From that perspective, the history of the symptom, of the child who
      owns it, and of the family in which this child is being raised are not emphasized
      as strongly. Searching for a specific meaning of such symptoms seems to be of no
      more interest. How can such a heavy trend be met? Major changes also have
      occurred within the psychoanalytic milieu. Advances from the observational world,
      from Spitz (1945) to Bowlby's (1987) attachment theory, provide essential
      knowledge to the field of early child-parent interactions. Longitudinal research
      in recent decades has shown close ties between early development and future
      outcomes. Such new knowledge is inspiring child analysis with very young children
      as well as with severely disturbed, older children. Early intervention with
      disadvantaged populations is showing the importance of the nonspecific aspects of
      the therapeutic relationship as a factor of change. In light of recent
      neurobiologic research on the influence of a specific environment-attachment
      experiences-on early development of the brain, it is now possible to speak of the
      social brain (Cozolino, 2006).

PMID- 28520159
TI  - A psychoanalytic view about "Clinical challenges of adoption, views from montreal
      and Tel Aviv".

PMID- 28520158
TI  - Focusing the lens: The infant's point of view. Discussion of "Brief interventions
      with parents, infants, and young children: A Framework for thinking".
AB  - This is a discussion of the article "Brief Interventions With Parents, Infants,
      and Young Children: A Framework for Thinking by Louise Emmanuel." Questions of
      symptom formation, the difference between a defense and developmental phenomena,
      and different therapeutic techniques are explored from the perspective of The
      Baby as Subject (an infant-parent psychotherapy approach developed at the Royal
      Children's Hospital in Melbourne, Australia). The relationship between feeding
      difficulties and the dynamics of the infant-parent attachment relationship are
      discussed with reference to whether the infant's apparent self-sufficiency is
      interpersonally generated and whether bids for autonomy are a sign of healthy,
      age-appropriate developmental drives at play. The use of representational toys in
      infant-parent psychotherapy to enable infants and toddlers to represent their
      experience or for the therapist to visually express what he or she understands
      the infant's experience to be and thus to work directly with the infant's
      representations is outlined. In addition to the linguistic content of verbal
      interpretations, the infant is receptive to the experience of another thinking
      mind and the emotional language, facial expressions, and gestures that also
      convey to the baby the experience of being understood or misunderstood.

PMID- 28520160
TI  - Challenges working with infants and their families: Symptoms and meanings-two
      approaches of infant-parent psychotherapy.
AB  - In this article, the authors describe the rationale for the way they work with
      troubled infant-parent relationships. They focus on two approaches developed at
      the Hincks-Dellcrest Children's Mental Health Centre (Toronto, Canada), a
      publically funded agency where they work and teach. One approach is Watch, Wait
      and Wonder, and the other is Infant-Parent Psychotherapy. The authors share a
      common philosophy that directs the way they think about the way they work. Two
      clinical case studies are presented to illustrate the treatment process of each
      approach. The presenting symptoms in both cases are similar (sleep difficulties),
      but the meaning, ages, and family compositions are different. The interventions
      unlocked the difficulties that each relationship was experiencing in a brief
      period of time.

PMID- 28520161
TI  - Opening remarks.

PMID- 28520162
TI  - Brief interventions with parents, infants, and young children: A framework for
      thinking.
AB  - In this article, I give an overview of the "Brief Intervention Model of work with
      Under Fives,'' focusing on ways in which observational skills, awareness of
      transference and countertransference phenomena, and addressing the underlying
      feelings thereby conveyed, can facilitate understanding and change. Two clinical
      vignettes illustrate the application of psychoanalytic thinking to work with the
      Under Fives Model and the fluctuating shifts of attention involved in trying to
      understand the meaning of what is being expressed. This includes the use of the
      clinicians' own emotional experience to work out "what the matter can be"
      (Emanuel & Bradley, 2008).

PMID- 28520163
TI  - The child WHO was born with no skin shield: Reflections on the meanings of
      therapy. Discussion of paper: "An infant WHO was born with a life-threatening
      skin disease: Various aspects of triadic psychotherapy".

PMID- 28520164
TI  - Transition-Metal Chalcogenide/Graphene Ensembles for Light-Induced Energy
      Applications.
AB  - Recently, nanomaterials that harvest solar energy and convert it to other forms
      of energy are of great interest. In this context, transition metal chalcogenides
      (TMCs) have recently been in the spotlight due to their optoelectronic properties
      that render them potential candidates mainly in energy conversion applications.
      Integration of TMCs onto a strong electron-accepting material, such as graphene,
      yielding novel TMC/graphene ensembles is of high significance, since photoinduced
      charge-transfer phenomena, leading to intra-ensemble charge separation, may
      occur. In this review, we highlight the utility of TMC/graphene ensembles, with a
      specific focus on latest trends in applications, while their synthetic routes are
      also discussed. In fact, TMC/graphene ensembles are photocatalytically active and
      superior as compared to intact TMCs analogues, when examined toward
      photocatalytic H2 evolution, dye degradation and redox transformations of organic
      compounds. Moreover, TMC/graphene ensembles have shown excellent prospect when
      employed in photovoltaics and biosensing applications. Finally, the future
      prospects of such materials are outlined.

PMID- 28520166
TI  - Operator-based variability of equine thromboelastography.
AB  - OBJECTIVE: To determine the extent of intraoperator (between duplicate samples)
      and interoperator (between different operators) variability in equine
      thromboelastography (TEG). DESIGN: Kaolin-activated TEG was performed in
      duplicate by operator-pair A/B or A/C (2 groups of 10 horses) using discrete
      setups, within 30-45 minutes of vacuum-assisted blood collection. Recorded TEG
      variables included clot initiation time (R), clot formation time (K), rate of
      clot formation (alpha), clot strength (MA), and viscoelastic/shear strength (G).
      Operators independently determined the clinical coagulation status for each
      sample. Intra- and interoperator variabilities were reported as coefficients of
      variation (CV), using descriptive statistics and paired samples t-test or
      Wilcoxon matched pair signed-rank test (P < 0.05 considered significant).
      ANIMALS: Twenty hospitalized adult horses with no clinical evidence of systemic
      inflammation. MEASUREMENTS AND MAIN RESULTS: Mean intraoperator CVs ranged from
      2.6 to 14% (operator A), 2.8 to 13% (operator B) and 1.2 to 18% (operator C).
      Both intra- and interoperator variabilities were lowest for MA (1.2-3.2%) and G
      (2.9-7.3%), and highest for K (13-23%). Mean CVs for all TEG parameters were
      lower when comparing intra- to interoperator variation. Seventy percent of horses
      had at least 1 TEG variable (out of 4 replicates) outside the established
      reference intervals. Assessment of coagulation status was conserved between
      operators in 9/10 and 8/10 horses for A/B and A/C, respectively, with comparable
      agreement between operator A/B (k = 0.73) and A/C (k = 0.74). CONCLUSIONS: TEG
      measurements of MA and G are more reproducible than assessment of K, within
      samples and between operators. The highest test variability was thus observed
      within the early phase of clot formation.

PMID- 28520168
TI  - Measures of infant behavioral and physiological state regulation predict 54-month
      behavior problems.
AB  - This study investigated whether measures of infant temperament, regulatory
      disorders, and physiological reactivity and concurrent measures of family
      environment were predictors of child behavior problems at 54 months of age. The
      sample consisted of 23 children-mother dyads. The sample recruitment strategy
      emphasized testing both typical and fussy/difficult infants at 9 months of age.
      Children were categorized into low and high behavioral problem groups at 54
      months of age. The children in the high behavioral problem group were more likely
      at 9 months to have been temperamentally difficult, to have been classified as
      regulatory disordered, and to have displayed respiratory sinus arrhythmia (RSA)
      regulation difficulties. These children also were more likely to come from
      families described as less cohesive and providing less focus on
      active/recreational activities when the children were 54 months old. A logistic
      regression analysis, including only the 9-month infant measures (i.e.,
      difficultness, regulatory disorders classification, and RSA regulation), resulted
      in a significant model with 100.0% accurate classification into high or low
      behavioral problem groups. Data suggest that infant measures of behavioral and
      physiological state regulation may be early indicators of child behavior
      problems, especially internalizing problems.

PMID- 28520167
TI  - KMT2B rare missense variants in generalized dystonia.
AB  - BACKGROUND: Recently a novel syndrome of childhood-onset generalized dystonia
      originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has
      been reported. METHODS: We sequenced the exomes of 4 generalized dystonia
      affected probands recruited from a Prague movement disorders center (Czech
      Republic). Bioinformatics analyses were conducted to select candidate causal
      variants in described dystonia-mutated genes. After cosegregation testing,
      checklists from the American College of Medical Genetics and Genomics were
      adopted to judge variant pathogenicity. RESULTS: Three novel, predicted protein
      damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val,
      p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from
      population-based controls, situated in a key protein domain, and had occurred de
      novo. The associated phenotype comprised adolescence-onset generalized isolated
      dystonia with prominent speech impairment. Although linked to a similar clinical
      expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance.
      CONCLUSIONS: Rare missense variation in KMT2B represents an additional cause of
      generalized dystonia. Application of sequence interpretation standards is
      required before assigning pathogenicity to a KMT2B missense variant. (c) 2017
      International Parkinson and Movement Disorder Society.

PMID- 28520165
TI  - Targeting CCl4 -induced liver fibrosis by RNA interference-mediated inhibition of
      cyclin E1 in mice.
AB  - : Initiation and progression of liver fibrosis requires proliferation and
      activation of resting hepatic stellate cells (HSCs). Cyclin E1 (CcnE1) is the
      regulatory subunit of the cyclin-dependent kinase 2 (Cdk2) and controls cell
      cycle re-entry. We have recently shown that genetic inactivation of CcnE1
      prevents activation, proliferation, and survival of HSCs and protects from liver
      fibrogenesis. The aim of the present study was to translate these findings into
      preclinical applications using an RNA interference (RNAi)-based approach. CcnE1
      siRNA (small interfering RNA) efficiently inhibited CcnE1 gene expression in
      murine and human HSC cell lines and in primary HSCs, resulting in diminished
      proliferation and increased cell death. In C57BL/6 wild-type (WT) mice, delivery
      of stabilized siRNA using a liposome-based carrier targeted approximately 95% of
      HSCs, 70% of hepatocytes, and 40% of CD45+ cells after single injection. Acute
      CCl4 -mediated liver injury in WT mice induced endogenous CcnE1 expression and
      proliferation of surviving hepatocytes and nonparenchymal cells, including CD45+
      leukocytes. Pretreatment with CcnE1-siRNA reverted CcnE1 induction to baseline
      levels of healthy mice, which was associated with reduced liver injury,
      diminished proliferation of hepatocytes and leukocytes, and attenuated overall
      inflammatory response. For induction of liver fibrosis, WT mice were challenged
      with CCl4 for 4-6 weeks. Co-treatment with CcnE1-siRNA once a week was sufficient
      to continuously block CcnE1 expression and cell-cycle activity of hepatocytes and
      nonparenchymal cells, resulting in significantly ameliorated liver fibrosis and
      inflammation. Importantly, CcnE1-siRNA also prevented progression of liver
      fibrosis if applied after onset of chronic liver injury. CONCLUSION: Therapeutic
      targeting of CcnE1 in vivo using RNAi is feasible and has high antifibrotic
      activity. (Hepatology 2017;66:1242-1257).

PMID- 28520169
TI  - Risks and outcomes associated with disorganized/controlling patterns of
      attachment at age three years in the National Institute of Child Health & Human
      Development Study of Early Child Care and Youth Development.
AB  - Disorganized/controlling attachment in preschool has been found to be associated
      with maternal and child maladjustment, making it of keen interest in the study of
      psychopathology. Additional work is needed, however, to better understand
      disorganized/controlling attachment occurring as early as age 3 years. The
      primary aims of this study were to evaluate risk factors and outcomes associated
      with disorganized/controlling behavior at age 3 years and to evaluate the risk
      factors and outcomes differentiating the four subtypes of
      disorganized/controlling attachment. Analyses were conducted with the first two
      phases of the National Institute of Child Health & Human Development Study of
      Early Child Care and Youth Development, a prospective study of 1,364 children
      from birth. At 36 months of age, across the attachment-relevant domains of
      maternal well-being, mother-child interactions, and child social adaptation, the
      disorganized/controlling group evidenced the most maladaptive patterns in
      comparison to both secure and insecure-organized groups. At 54 months of age, the
      disorganized/controlling group displayed the highest levels of internalizing and
      externalizing behavior problems, as rated by mothers and teachers, and the lowest
      quality relationships with teachers. Significant differences found among the
      disorganized/controlling subtypes indicated that the behaviorally disorganized
      and controlling-punitive subtypes had more maladaptive patterns across variables
      than did the controlling-caregiving and controlling-mixed subtypes.

PMID- 28520170
TI  - A social-contextual understanding of concordance and discordance between maternal
      prenatal representations of the infant and infant-mother attachment.
AB  - This prospective study examined the relationship between maternal prenatal
      representations of the infant and later infant-mother attachment, including
      contextual factors related to concordance and discordance among dyads over time.
      Participants were 173 pregnant women between the ages of 18 and 40 who were
      interviewed during their last trimester of pregnancy and 2 and 13 months after
      birth. Maternal representations were assessed by the Working Model of the Child
      Interview during pregnancy (WMCI; C.H. Zeanah, D. Benoit, L. Hirshberg, M.L.
      Barton, & C. Regan, 1994), and infant-mother attachment was assessed through the
      Strange Situation procedure (M.D.S. Ainsworth, M. Blehar, E. Waters, & S. Wall,
      1978) when infants were 13 months old. There was substantial discordance between
      maternal and infant classifications, although a significant concordance rate was
      found when classifications were collapsed into balanced/secure and
      nonbalanced/insecure groups based on prenatal representations and postnatal
      infant attachment groups (60%; chi2 = 6.90, p < .01; kappa .20). As expected,
      discordance between maternal representations and infant-mother attachment was
      meaningfully related to contextual risk factors, maternal depression, and infant
      behaviors.

PMID- 28520171
TI  - Music therapy with hospitalized infants-the art and science of communicative
      musicality.
AB  - Infants seek contingent, companionable interactions with others. Infants in a
      Neonatal Intensive Care Unit (NICU), while receiving care that optimizes their
      chances of survival, often do not have the kind of interactions that are optimal
      for their social development. Live music therapy (MT) with infants is an
      intervention that aims for contingent, social interaction between therapist and
      infant. This study, with a limited numbers of infants, examined the effectiveness
      of an MT intervention in the NICU at The Royal Children's Hospital Melbourne. Two
      groups of late pre-term and full-term infants were recruited to the study; one
      was given MT and the other was not. A healthy group of infants not given MT
      served as an additional control. The effect of MT was indexed using two measures
      reflecting infant social engagement: the Neurobehavioral Assessment of the
      Preterm Infant (NAPI) and the Alarm Distress Baby Scale (ADBB). Results suggest
      that the MT intervention used at The Royal Children's Hospital Melbourne supports
      infants' neurobehavioral development. In particular, hospitalized infants who
      received MT were better able to maintain self-regulation during social
      interaction with an adult, were less irritable and cried less, and were more
      positive in their response to adult handling, when compared with infants who did
      not receive the intervention. These are important prerequisites for social
      interaction and development. Further and larger scale research using MT with this
      population is indicated.

PMID- 28520172
TI  - Infancy research, infant mental health, and adult psychotherapy: Mutual
      influences.
AB  - This article considers the influence of infant research on psychodynamic theory
      and practice. Infant research highlights the dramatic effects of the early
      caregiving relationship on development throughout the life span. It also provides
      important perspectives on psychotherapeutic processes. This article highlights
      such elements as empathy, mutual recognition and attachment, along with
      elaborating the intersubjective and transactional systems perspectives. In
      addition, it stresses the powerful role of nonverbal, implicit communication and
      meaning-making, which play a greater role in human relational experience-and
      therefore in the therapeutic process-than previously understood. In addition to
      clarifying these general orientations, the article describes specific therapeutic
      strategies based on the expanded developmental knowledge.

PMID- 28520173
TI  - Mothers' voices: Coping with their children's initial disability diagnosis.
AB  - For parents of infants and toddlers receiving a diagnosis of disability, a
      variety of responses may result. Yet, little is known about the specific ways
      families cope with the initial diagnosis. This qualitative study investigated 6
      mothers' memories of their children's diagnoses. Mothers described their use of
      both palliative strategies (denying, questioning, and wishful thinking) and
      problem-solving strategies (searching for information, seeking social support,
      reframing, and seeking spiritual support) to cope with their children's initial
      diagnoses. The results of this study may improve professionals' understanding of
      parents' need for information and support at the time of initial diagnosis.

PMID- 28520174
TI  - Maternal perceptions of the infant: Relationship to maternal self-efficacy during
      the first six weeks' postpartum.
AB  - Mothers' perceptions of their infants and their own levels of self-efficacy
      contribute to developing maternal-infant attunement. The purpose of this
      investigation was to examine the associations between maternal perceptions of
      their own infants relative to other infants and maternal self-efficacy in a group
      of ethnically diverse, low-income, first-time mothers during the first six weeks
      postpartum. By employing a structural equation model approach, we explored
      relationships between the predictor (maternal neonatal perceptions) and dependent
      variable (maternal self-efficacy). Changes in maternal perceptions of their own
      infants significantly contributed to self-reported levels of self-efficacy while
      controlling for concurrent self-esteem. Maternal perceptions of her infant as
      less difficult than the average infant at six weeks postpartum predicted
      increased levels of maternal self-reported self-efficacy. The present study
      supports further exploration of the first six weeks postpartum as a sensitive
      period for targeting intervention and support, particularly for mothers and
      infants at highest risk.

PMID- 28520175
TI  - Assessing the prevalence of mental health disorders and mental health needs among
      preschool children in care in England.
AB  - Although school-aged children living in foster care have been identified as a
      high-risk group for mental health and developmental disorders, there is a paucity
      of data relating to preschool children in care (CIC). This study aimed to
      identify the prevalence of mental health and developmental disorders along with
      corresponding need for interventions in preschool CIC. All CIC aged 0 to 5 years
      in an inner city local authority underwent comprehensive, multifaceted
      assessments consisting of the Ages and Stages Questionnaire (J. Squires, D.
      Bricker, & E. Twombly, 2003), interviews with caregivers based on the Preschool
      Age Psychiatric Assessment (H.L. Egger & A. Angold, 2006), Mullen Scales of Early
      Learning (E.M. Mullen, 1995), and systematic clinical observation. Of 58 eligible
      preschoolers, 43 completed the assessment. At least one mental health disorder
      was found in 26 (60.5%) participants, and at least one developmental disorder was
      found in 11 (25.6%). When mental health and/or developmental disorders were
      considered together, 30 (69.8%) preschoolers fulfilled criteria for at least one
      diagnosis, and 18 (41.9%) had two or more comorbid conditions. Whereas 36 (83.7%)
      of the preschoolers needed an intervention, only 3 of these had received adequate
      input. In conclusion, preschool CIC constitute a high-risk group for mental
      health and developmental disorders. Without age-appropriate assessments, their
      needs go undetected, and opportunities for early intervention are being missed.

PMID- 28520176
TI  - What we talked about at the pediatrician's office: Exploring differences between
      healthy steps and traditional pediatric primary care visits.
AB  - Healthy Steps for Young Children (HS) is a program designed to enhance pediatric
      primary care experiences for children birth to 3 years and their families by
      pairing a developmental specialist with a pediatric provider during well-child
      visits. This study examined the impact of HS on content discussed during well
      child visits by providers, HS Specialists, and families. The impact of HS on
      pediatric outcomes, including timeliness of well-child visits and immunizations,
      also was examined. Using retrospective medical review, records of 40 children
      enrolled in HS were compared with records of 36 demographically matched controls.
      A developmental topics checklist was used to analyze content of well-child
      visits. Attendance at well-child visits, receipt of immunizations, and healthcare
      utilization also was evaluated. Important developmental topics were discussed
      more often during well-child visits of children enrolled in HS than for children
      who were not enrolled. Children enrolled in HS received timelier well-child
      visits and immunizations. No differences between groups were found in the number
      of sick or emergency room visits. Integrating HS Specialists into pediatric
      primary care well-child visits allows for discussion of important developmental
      topics while also impacting pediatric health outcomes.

PMID- 28520177
TI  - Predicting maternal sensitivity: The roles of postnatal depressive symptoms and
      parasympathetic dysregulation.
AB  - Previous research has established that maternal depression is a risk factor for a
      variety of negative developmental outcomes among infants and children. Although
      low levels of maternal sensitivity have been hypothesized to explain this risk,
      the biological mechanisms underlying the association between maternal depressive
      symptoms and low levels of maternal sensitivity have been largely underexplored.
      This study examined the roles of postnatal depressive symptoms and
      parasympathetic nervous system functioning as predictors of low levels of
      maternal sensitivity, during a stressful mother-infant interaction-the reunion
      phase of the Still-Face Paradigm. Depressive symptoms and traitlike
      predispositions toward parasympathetic dysregulation, as indexed by low resting
      levels of respiratory sinus arrhythmia, were associated independently with less
      sensitive parenting. Discussion considers that during stressful mother-infant
      interactions, both mothers with depressive symptoms and mothers predisposed to
      parasympathetic dysregulation may have fewer emotional, physiological, and
      psychological resources with which to respond sensitively to their infants' cues.

PMID- 28520178
TI  - Postnatal mental health and parenting: The importance of parental anger.
AB  - Parents' postnatal mental health and subjective perceptions of their baby are
      likely to influence the quality of their relationship with their baby. To date,
      this has largely been examined in mothers; therefore, this study aimed to also
      explore this in both parents. Semistructured clinical interviews [The Birmingham
      Interview for Maternal Mental Health (BIMMH); Brockingon, Chandra et al., 2006]
      were carried out with 85 first-time parents. The BMMHI identifies disorders of
      anxiety, depression, PTSD, and parental anger. Sections of the BMMHI also elicit
      qualitative accounts of parenthood. These were transcribed and analyzed using
      thematic analysis. Differences in the frequency of themes were examined for
      parents with or without mental health disorders or parental anger. Themes are
      reported for (a) baby characteristics, needs, and development; (b) parents'
      emotions, responses, coping strategies, and general parenthood; and (c) parent
      and baby relationship. Results indicated that both the presence of parental
      mental health problems and, more notably, parental anger were associated with
      more negative accounts of the self, the baby, and parenthood. This study provides
      insight into first-time parents' perceptions of early parenthood. Results
      especially highlight the need to consider parental experiences of anger in more
      detail for assessment and interventions in the early postpartum period.

PMID- 28520179
TI  - The role of transitions to new age groups in the development of institutionalized
      children.
AB  - Children in two institutions in St. Petersburg (Russian Federation) experienced
      ward transitions, one in which caregivers were trained to provide sensitive,
      responsive caregiving and one that conducted business as usual. A third
      institution eliminated transitions, received the same training, and implemented a
      variety of structural and employment changes designed to promote improved
      caregiver-child interactions and relationships. While the no-transition
      comprehensive intervention group of children steadily improved in Battelle
      Developmental Inventory (LINC Associates, 1988) scores across all age intervals,
      the children in the institution who encouraged some positive caregiver-child
      interactions improved before and after, but not during, an age period that
      involved a transition. In contrast, the no-treatment group displayed no
      developmental changes across any age period with or without a transition. These
      results suggest that the common institutional practice of ward transitions to new
      peers and caregivers is potentially disruptive to infants' and toddlers' general
      development, but primarily in a context in which some degree of caregiver-child
      sensitive and responsive interactions are encouraged.

PMID- 28520180
TI  - SIRT3 as a regulator of hepatic autophagy.

PMID- 28520181
TI  - Encapsulation and Polymerization of White Phosphorus Inside Single-Wall Carbon
      Nanotubes.
AB  - Elemental phosphorus displays an impressive number of allotropes with highly
      diverse chemical and physical properties. White phosphorus has now been filled
      into single-wall carbon nanotubes (SWCNTs) from the liquid and thereby stabilized
      against the highly exothermic reaction with atmospheric oxygen. The encapsulated
      tetraphosphorus molecules were visualized with transmission electron microscopy,
      but found to convert readily into chain structures inside the SWCNT
      "nanoreactors". The energies of the possible chain structures were determined
      computationally, highlighting a delicate balance between the extent of
      polymerization and the SWCNT diameter. Experimentally, a single-stranded zig-zag
      chain of phosphorus atoms was observed, which is the lowest energy structure at
      small confinement diameters. These one-dimensional chains provide a glimpse into
      the very first steps of the transformation from white to red phosphorus.

PMID- 28520182
TI  - Intraductal papillary neoplasm of the bile duct: A rare liver tumor complicated
      by malignancy.

PMID- 28520184
TI  - Infant feeding and infant health in American Samoa.
AB  - This study examines the association between infant feeding patterns and health
      for 6,267 Samoan children born between 1976 and 1982, and represented in the Well
      Baby Clinic records at the LBJ Tropical Medical Center, American Samoa. The
      visits to the clinic were aggregated by trimester of age during the first year of
      life. For each trimester, the principal source of milk was determined, and the
      children were categorized as breast-fed if they were taking only breast milk,
      bottle-fed if they were getting no breast milk, or mixed-fed if they were getting
      both breast milk and milk from other sources. Symptoms and complaints noted in
      the records were assigned to ICD categories. Associations between source of milk
      and disease category were analyzed. The Samoan infants were found to be quite
      healthy for a tropical developing population, as evidenced by both growth in
      weight and length, as well as by frequency of illnesses. The most common specific
      disease category, aside from miscellaneous symptoms, was ICD 8, respiratory
      problems. Gastrointestinal diseases were rare for a developing area. There was an
      association between source of milk and illness (yes/no) for both the second and
      third trimesters. In both cases breast-fed infants were healthier than the mixed
      fed infants, and during the second trimester the contrast was significant with
      bottle-fed infants also. When examined by ICD category, breast-fed infants tended
      to be less likely to have problems in any of the categories, but the only
      significant differences were between mixed-fed (lower prevalence) and bottle-fed
      infants during the first trimester for ICD 3, primarily nutritional problems; and
      for breast-fed (lower prevalence) and mixed-fed infants for ICD 9, digestive
      problems. These findings highlight the need for additional household work to
      delineate associations with the growth and health of Samoan infants.

PMID- 28520183
TI  - Infected malnourished children displayed changes in early activation and
      lymphocyte subpopulations.
AB  - AIM: Malnutrition and infections cause immunological changes in lymphocyte
      subpopulations and their functionality. We evaluated the activation capacity of
      lymphocytes and memory cells in 10 well nourished, seven well-nourished infected
      and eight malnourished infected children before and after treatment. METHODS: All
      the children were patients in Mexico City and were less than three years of age.
      The expression of various cluster of differentiation (CD) cells was assessed by
      flow cytometry: CD45RA (naive) and CD45RO (memory) antigens on CD4 lymphocytes
      and CD69 in all lymphocytes. RESULTS: Well-nourished infected children showed a
      higher percentage of activated T lymphocyte (T cells), CD8+ and CD4+ memory cells
      during the infectious phase, suggesting that the activation mechanisms were
      triggered by infection. T cells from malnourished infected children showed a
      lower percentage of activated and memory cells. The T cell population size
      returned to baseline during the resolution phase of the infection in well
      nourished infected children, but their T, B lymphocyte and natural killer (NK)
      cell counts remained high. In malnourished infected children, activated NK cells
      counts were low before and after therapy. CONCLUSION: After therapy, malnourished
      infected children showed poor NK cell responses during the infection's resolution
      phase, suggesting a persistent malnutrition-mediated immunological deficiency.

PMID- 28520185
TI  - Correlates of enamel hypoplasia with human dental reduction.
AB  - Human dental reduction has been manifested in evolutionary and secular trends,
      but it is not known to what degree each of these complementary processes
      contributes to changes in tooth size. Enamel hypoplasia is a marker of
      developmental stress that is often found to be of greater frequency and severity
      in populations undergoing dental size reduction. In order to test the
      developmental association of enamel hypoplasia with tooth size, measurements of
      bucco-lingual and mesio-distal diameters were taken on teeth of 54 black male
      skulls from southern Africa. Those dentitions that exhibited incisal enamel
      hypoplasia were significantly reduced in size as compared to those showing no
      signs of developmental stress. A distinct pattern of reduction emerged: the bucco
      lingual diameters of the I1 , I2 , P3 , P4 , M1 , and M2 were significantly
      reduced, whereas the mesio-distal diameters of only the I2 and M2 decreased in
      size. The I2 and M2 showed the greatest degree of reduction despite the lack of
      macroscopic enamel hypoplasia on the M2 . Application of the data to the variety
      of dental reduction patterns evinced in modern and ancient populations indicates
      that factors including tooth shape, developmental timing of stress, and genetic
      determinants of tooth size must be considered in order to partition evolutionary
      and secular trends in the dentition.

PMID- 28520186
TI  - Preterm baby delivery: Some genetic epidemiological aspects.
AB  - The present paper considers genetic risk factors associated with preterm births.
      We investigated two main hypotheses, namely: 1) Whether there is a detectable
      genetic or at least a family resemblance component that may predispose a mother
      to give birth prematurely and 2) whether the risk to preterm delivery can be
      predicted in the early stages of pregnancy by means of associated morphometric
      traits and biochemical genetic markers. Our data and published literature
      certainly point to the existence of a significant family component, although the
      findings are still scanty for precise determination of genetic and cultural
      heritability components. In particular, the available data on family correlations
      in gestational age do not allow one to distinguish between the contribution of
      the fetus's genotype from the maternal environment and maternal genotype. Parent
      children and marital correlations in gestational age, critical for nuclear family
      analysis, are rather difficult, if not impossible, to obtain. Therefore, we
      discuss in the present paper several realistic path analysis models for
      estimating the relative contribution of genetically inherited and environmental
      components. Some biochemical markers and also morphological asymmetry correlate
      with a predisposition to preterm delivery. Again, however, more empirical data
      are needed to properly assess these relationships.

PMID- 28520187
TI  - Reliability of Tanner stage assessments in a multi-center study.
AB  - Tanner stage indices have been frequently used in research studies to
      characterize the level of sexual maturation among adolescents. The Cooperative
      Study of Sickle Cell Disease (CSSCD) is a large multi-center study in which the
      assessment of Tanner stage indices has been performed to describe delays in
      sexual maturation and correlates of delays. Rigorous training, however, in rating
      Tanner stages was not provided for the clinicians in the study. Data from the
      CSSCD were analyzed to characterize the reliability of the assessment of sexual
      maturation in this study, and demonstrate the potential for increasing the
      reliability by more careful training. In lieu of a gold standard, a maximum
      likelihood algorithm was employed to examine the longitudinal consistency of
      Tanner stage assessments. Based on the assumption that the underlying process of
      sexual maturation is progressive, models were developed that allowed one to
      estimate jointly the incidence distribution for the attainment of Tanner stages
      and the error rates of assessment. Estimated false-positive rates for assessing
      the attainment of Tanner stages from the CSSCD ranged from 2% to 19%. Estimated
      false-negative rates ranged from 1% to 18%. The occurrence of these errors was
      found not to vary markedly with the subject's age. Error rates of this magnitude
      can introduce considerable bias to the estimation of the distribution of Tanner
      stages and result in serious losses in relative efficiency. While the validity of
      Tanner stage indices can be demonstrated from study data, the loss in statistical
      efficiency and power associated with the study error rates was severe. This
      underscores the utility of careful training in pubertal rating for research
      studies.

PMID- 28520188
TI  - Evaluation of physical growth of children in a rainforest community of
      northwestern Ecuador.
AB  - The physical growth of children under 5 years of age was studied in relation to
      patterns of nutrition, morbidity, and health care utilization in three remote
      villages of tropical Ecuador. Age-specific comparisons of height and weight to
      growth curves from reference populations (US National Child Health Survey)
      indicated moderate to severe stunting in the population of male and female
      children. Examination of height-weight relationships as a measure of recent
      nutritional status provided little evidence that male children were underweight
      for their height. However, the observation that female children fell between the
      3rd and 50th centile channels of the reference population in their height-weight
      relationship suggested moderate wasting in addition to substantial stunting.
      Endemic parasitism and a high rate of diarrheal illnesses were detected in the
      study population and were likely contributing agents to the stunting observed in
      male and female children. No dichotomy in the incidence of diarrhea was detected
      between male and female children, and if the episode was mild it was typical not
      to treat the illness, regardless of sex. In more severe cases, female children
      were more frequently taken to traditional healers. However, when familial self
      treatment or local clinics were used, male children were more likely to be the
      beneficiary. Thus it seems possible that this advantage, along with the cultural
      practice of investing more of the family's resources in male children, may be
      responsible for the wasting detected in young females. Tropical conditions,
      chronic undernutrition, compromised cellular immunity, and inadequate health care
      services were likely causes of the high morbidity and mortality of children under
      age 5. Community-based programs of health promotion and disease prevention appear
      to offer the best potential as intervention strategies in these villages.

PMID- 28520189
TI  - Determining growth faltering with a tracking score.
AB  - A tracking score for determining growth faltering in children was developed and
      tested. A graphical method was developed for classifying by visual inspection
      whether or not a given child had faltered in growth. This method was used to
      classify all children in a sample of Guatemalan children as to faltering in both
      weight and length between 9 and 24 months of age; 80 of 345 children had faltered
      in weight, and 44 of 336 children had faltered in length. The accuracies for
      determining this faltering of seven versions of the tracking score and that of
      three other commonly used scores were assessed and compared using ROC curves, the
      areas under the curves, and two other ways. The other scores tested were the
      increment score, the residual score, and a growth-curve parameter score. The
      accuracies of the scores were overall lower for weight than for length. For both
      weight and length, the growth-curve parameter score had the lowest accuracy, and
      the tracking score that used an intermediate number of measurements (four in the
      interval of interest and three in the previous interval) had the highest
      accuracy. The tracking score has a number of features that make it attractive as
      an indicator of faltering. It is easy to calculate and interpret, preserves
      magnitude and direction, incorporates several growth measurements into a single
      indicator of faltering, gives equal weight to the information in all the
      measurements used, allows for missing measurements, and can be generalized to
      include other aspects of growth.

PMID- 28520190
TI  - Long bone growth velocity in the Libben population.
AB  - Growth-attained curves have shown only limited effectiveness in studies of long
      bone growth in archaeological populations. As an alternative, the length of long
      bone diaphyses in children aged 0 to 12 years from the Libben skeletal collection
      were first normalized by average adult long bone length, and derivatives of
      fitted curves were then used to determine age-specific growth velocity. The
      sample was compared to healthy Euroamerican children from Denver, Colorado
      (Maresh: American Journal of Diseases of Children 89:725-742, 1955). Results
      indicate almost identical patterns of growth in the two populations with one
      exception: the Libben sample shows significantly diminished velocity during the
      first three years of life. This period of depressed growth coincides with high
      levels of infectious disease.

PMID- 28520191
TI  - Effect of tooth size on the ageing and chronological distribution of enamel
      hypoplastic defects.
AB  - The location of enamel hypoplastic defects on the tooth crown has been used to
      determine the age of an individual at the time the defect-producing stress
      occurred. The assumptions made in following this methodology are examined, and
      one in particular, that tooth size variation has a minimal impact on ageing and
      subsequent chronological distributions, is tested. Teeth with no occlusal or
      minimal wear and with enamel hypoplasias were measured for crown height and the
      location of the defect on the crown. Two samples are used, one comprising a
      series of archaeological specimens and the other from modern clinical
      extractions. The chronological distributions of the defects are determined by
      three different methods: one is based on a tooth mineralization chart; the second
      method uses the same chart but incorporates individual crown heights; and the
      third method adjusts the chart for the sample's mean crown heights. Significant
      differences between the age estimates are observed in both the modern and
      archaeological samples. Tooth size does affect the ageing of hypoplastic defects
      and the chronological distributions. By adjusting the mineralization chart for
      the sample's mean crown heights, the significant differences in age estimates can
      be corrected.

PMID- 28520192
TI  - A GAUSS program for computing an index of tracking from longitudinal
      observations.
AB  - Tracking can be defined as the tendency of individuals or collections of
      individuals to stay within a particular course of growth over time relative to
      other individuals. Thus, tracking describes stability in growth patterns. This
      paper outlines a statistical procedure for examining tracking in a single sample
      of measurements made on humans or other animals. This nonparametric procedure,
      based on Cohen's (1960) kappa statistic, is suitable for equally or unequally
      spaced serial data that is complete and is appropriate for questions concerning
      growth as well as other time-dependent phenomena. It is a conceptually simple
      longitudinal method that affords insight regarding the predictability of growth
      within a population. For example, by tracking, one can ask if young children who
      are in the lowest height for age category are likely to end up in that category
      at an older age. A user-friendly GAUSS program is provided that generates overall
      as well as individual and track-specific statistics. High-resolution graphic
      representations of the data are also generated by the program. Examples are
      presented, including a tracking analysis of Guatemalan Indian children using
      quartiles.

PMID- 28520193
TI  - Two evolutionary models for the interactions of dietary organic cyanogens,
      hemoglobins, and falciparum malaria.
AB  - Significant regional and ethnic variations in hemoglobin S frequencies among 485
      adult nonpregnant Liberian women uniformly exposed to holoendemic falciparum
      malaria suggest that an additional major factor may influence the distribution of
      this hemoglobinopathy and the severity of the infectious disease with which it is
      causally associated. The differential consumption of organic cyanogen-rich
      cassava (Manihot esculenta) foodstuffs and subsequent dosage-dependent in vivo
      exposure to sublethal CN- , SCN- , and CNO- may directly interact with hemoglobin
      S by inhibiting sickling diathesis, and, at higher intakes, this dietary factor
      may adversely affect Plasmodium survival and antigenicity. In this study, low
      dietary organic cyanogen intakes (0.3 mg CN- /kg body wt/day) in NW and W
      geographical areas are associated with higher regional hemoglobin S gene
      frequencies (11%; phenotypic incidence 20%), lower mean (+/- SD) positive
      Plasmodium antibody titers (861.6 +/- 102.4), and a higher mean (+/- SEM)
      prevalence of clinical falciparum malaria [3.04 times (+/- 0.09) within the
      previous 12 months]. In contrast, high dietary organic cyanogen intakes (1.5 mg
      CN- /kg body wt/day in SE and C geographical areas) are associated with lower
      hemoglobin S gene frequencies (2%; phenotypic incidence 4%), higher mean (+/- SD)
      positive Plasmodium antibody titers (968.7 +/- 160.5), and a lower mean (+/- SEM)
      prevalence of clinical falciparum malaria [1.73 times (+/- 0.11) within the
      previous 12 months]. No other significant malaria-linked genetic variation exists
      between regions or ethnic groups. Two evolutionary models are hypothesized to
      suggest how 18 generations of differential dietary organic cyanogen intakes could
      produce two distinct patterns of change in hemoglobin S gene frequencies,
      modifying both the cadence and direction of evolution.

PMID- 28520194
TI  - Basal metabolism of obese adolescents: Evidence for energy conservation compared
      to normal and lean adolescents.
AB  - To test if obese adolescents systematically conserve energy, comparisons of basal
      metabolic rate (BMR) of obese, normal, and lean male and female adolescents were
      made. Obese had eleevated values by as much as 23% (P <= 0.05) expressed as kJ .
      24 hr-1 compared to the normal and lean. When indexed to body mass (kJ . kg-BM-1
      . hr-1 ), the BMR for the obese was depressed by as much as -53% (P <= 0.01), and
      when indexed to fat free mass (kJ . kg-FFM-1 . hr-1 ) it was depressed by -33%
      compared to normal and lean adolescents. A "theoretical metabolic rate" (TMR),
      based on the observed fat free mass, fat mass, and their thermal equivalents, was
      proposed as a theoretical way to properly index basal metabolism, referenced to
      body composition. Comparisons of the TMR between the obese, normal, and lean
      revealed that the obese values were depressed by an average -22% (P <= 0.05). In
      comparison, differences in TMR between the normal and lean males and females were
      no larger than 8% (ns). It was concluded that since both the observed BMR
      (expressed relative to body composition), and the derived TMR values were
      depressed for the obese compared to the normal and lean adolescent, the data
      suggest an energy saving hypothesis for obese adolescents.

PMID- 28520195
TI  - Anthropometric somatotype of Bod girls: A comparison of high and low altitude
      populations.
AB  - The high altitude environment is known to influence the morphophysiology of man
      in a variety of ways. Its possible impact on somatotype of adolescent girls has
      not been investigated so far. For this purpose 348 female Bods, from 10 to 18
      years old, have been somatotyped from high altitude (n = 176) of Ladakh (3,534 m)
      and low altitude (n = 172) of Kullu Valley (1,500-2,200 m). The results of the
      study reveal greater mesomorphy and ectomorphy in the high altitude Bod girls
      than in ethnically similar low altitude Bod girls of comparable age. The study
      has accorded the differences in the somatotypes to the high altitude stresses.
      Striking similarities in boys and girls in terms of higher mesomorphy and
      ectomorphy in the highlander Bods than the coeval lowlanders confirm the
      hypothesis that the high altitude environment influences the somatotype
      components.

PMID- 28520197
TI  - Integrated Uncertainty Analysis for Ambient Pollutant Health Risk Assessment: A
      Case Study of Ozone Mortality Risk.
AB  - The U.S. Environmental Protection Agency (EPA) uses health risk assessment to
      help inform its decisions in setting national ambient air quality standards
      (NAAQS). EPA's standard approach is to make epidemiologically-based risk
      estimates based on a single statistical model selected from the scientific
      literature, called the "core" model. The uncertainty presented for "core" risk
      estimates reflects only the statistical uncertainty associated with that one
      model's concentration-response function parameter estimate(s). However,
      epidemiologically-based risk estimates are also subject to "model uncertainty,"
      which is a lack of knowledge about which of many plausible model specifications
      and data sets best reflects the true relationship between health and ambient
      pollutant concentrations. In 2002, a National Academies of Sciences (NAS)
      committee recommended that model uncertainty be integrated into EPA's standard
      risk analysis approach. This article discusses how model uncertainty can be taken
      into account with an integrated uncertainty analysis (IUA) of health risk
      estimates. It provides an illustrative numerical example based on risk of
      premature death from respiratory mortality due to long-term exposures to ambient
      ozone, which is a health risk considered in the 2015 ozone NAAQS decision. This
      example demonstrates that use of IUA to quantitatively incorporate key model
      uncertainties into risk estimates produces a substantially altered understanding
      of the potential public health gain of a NAAQS policy decision, and that IUA can
      also produce more helpful insights to guide that decision, such as evidence of
      decreasing incremental health gains from progressive tightening of a NAAQS.

PMID- 28520196
TI  - Environmentally Friendly Recycling of Fuel-Cell Membrane Electrode Assemblies by
      Using Ionic Liquids.
AB  - The platinum nanoparticles used as the catalyst in proton exchange membrane fuel
      cells (PEMFCs) represent approximately 46 % of the total price of the cells for a
      large-scale production, and this is one of the barriers to their
      commercialization. Therefore, the recycling of the platinum catalyst could be the
      best alternative to limit the production costs of PEMFCs. The usual recovery
      routes for spent catalysts containing platinum are pyro-hydrometallurgical
      processes in which a calcination step is followed by aqua regia treatment, and
      these processes generate fumes and NOx emissions, respectively. The
      electrochemical recovery route proposed here is more environmentally friendly,
      performed under "soft" temperature conditions, and does not result in any gas
      emissions. It consists of the coupling of the electrochemical leaching of
      platinum in chloride-based ionic liquids (ILs), followed by its
      electrodeposition. The leaching of platinum was studied in pure ILs and in ionic
      liquid melts at different temperatures and with different chloride contents.
      Through the modulation of the composition of the ionic-liquid melts, it is
      possible to leach and electrodeposit the platinum from fuel-cell electrodes in a
      single-cell process under an inert or ambient atmosphere.

PMID- 28520198
TI  - Dynamic and steady-state oxygen-dependent lung relaxometry using inversion
      recovery ultra-fast steady-state free precession imaging at 1.5 T.
AB  - PURPOSE: To demonstrate the feasibility of oxygen-dependent relaxometry in human
      lung using an inversion recovery ultra-fast steady-state free precession (IR
      ufSSFP) technique. METHODS: Electrocardiogram-triggered pulmonary relaxometry
      with IR-ufSSFP was performed in 7 healthy human subjects at 1.5 T. The data were
      acquired under both normoxic and hyperoxic conditions. In a single breath-hold of
      less than 9 seconds, 30 transient state IR-ufSSFP images were acquired, yielding
      longitudinal (T1) and transversal (T2) relaxometry parameter maps using voxel
      wise nonlinear fitting. Possible spatial misalignments between consecutive IR
      ufSSFP parameter maps were corrected using elastic image registration.
      Furthermore, dynamic relaxometry oxygen wash-in and wash-out scans were performed
      in one volunteer. From this, T1 -related wash-in and wash-out time constants
      (tauwi , tauwo ) were calculated voxel-wise on registered maps using an
      exponential fitting model. RESULTS: For healthy lung, observed T1 values were
      1399 +/- 77 and 1290 +/- 76 ms under normoxic and hyperoxic conditions,
      respectively. Oxygen-related reduction of T1 was statistically significant in
      every volunteer. No statistically significant change, however, was observed in
      T2, with normoxic and hyperoxic T2 values of 55 +/- 16 and 56 +/- 17 ms,
      respectively. The observed average tauwi was 87.0 +/- 28.7 seconds, whereas the
      average tauwo was 73.5 +/- 21.6 seconds. CONCLUSION: IR-ufSSFP allows fast,
      steady-state, and dynamic oxygen-dependent relaxometry of the human lung. Magn
      Reson Med 79:839-845, 2018. (c) 2017 International Society for Magnetic Resonance
      in Medicine.

PMID- 28520199
TI  - Economic evaluation of strategies for restarting anticoagulation therapy after a
      first event of unprovoked venous thromboembolism.
AB  - : Essentials Correct duration of treatment after a first unprovoked venous
      thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was
      worthwhile based on patient risk of recurrent VTE. When the risk over a one-year
      period is 17.5%, restarting is cost-effective. However, sensitivity analyses
      indicate large uncertainty in the estimates. SUMMARY: Background Following at
      least 3 months of anticoagulation therapy after a first unprovoked venous
      thromboembolism (VTE), there is uncertainty about the duration of therapy.
      Further anticoagulation therapy reduces the risk of having a potentially fatal
      recurrent VTE but at the expense of a higher risk of bleeding, which can also be
      fatal. Objective An economic evaluation sought to estimate the long-term cost
      effectiveness of using a decision rule for restarting anticoagulation therapy vs.
      no extension of therapy in patients based on their risk of a further unprovoked
      VTE. Methods A Markov patient-level simulation model was developed, which adopted
      a lifetime time horizon with monthly time cycles and was from a UK National
      Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base
      case model results suggest that treating patients with a predicted 1 year VTE
      risk of 17.5% or higher may be cost-effective if decision makers are willing to
      pay up to L20 000 per quality adjusted life year (QALY) gained. However,
      probabilistic sensitivity analysis shows that the model was highly sensitive to
      overall parameter uncertainty and caution is warranted in selecting the optimal
      decision rule on cost-effectiveness grounds. Univariate sensitivity analyses
      indicate variables such as anticoagulation therapy disutility and mortality risks
      were very influential in driving model results. Conclusion This represents the
      first economic model to consider the use of a decision rule for restarting
      therapy for unprovoked VTE patients. Better data are required to predict long
      term bleeding risks during therapy in this patient group.

PMID- 28520202
TI  - Haemophilia treatment for all and the role of tolerance, difference and
      education.

PMID- 28520200
TI  - Hepatic infiltration by silicone in a patient With ASIA syndrome.

PMID- 28520201
TI  - Communication practices that encourage and constrain shared decision making in
      health-care encounters: Systematic review of conversation analytic research.
AB  - BACKGROUND: Shared decision making (SDM) is generally treated as good practice in
      health-care interactions. Conversation analytic research has yielded detailed
      findings about decision making in health-care encounters. OBJECTIVE: To map
      decision making communication practices relevant to health-care outcomes in face
      to-face interactions yielded by prior conversation analyses, and to examine their
      function in relation to SDM. SEARCH STRATEGY: We searched nine electronic
      databases (last search November 2016) and our own and other academics'
      collections. INCLUSION CRITERIA: Published conversation analyses (no restriction
      on publication dates) using recordings of health-care encounters in English where
      the patient (and/or companion) was present and where the data and analysis
      focused on health/illness-related decision making. DATA EXTRACTION AND SYNTHESIS:
      We extracted study characteristics, aims, findings relating to communication
      practices, how these functioned in relation to SDM, and internal/external
      validity issues. We synthesised findings aggregatively. RESULTS: Twenty-eight
      publications met the inclusion criteria. We sorted findings into 13 types of
      communication practices and organized these in relation to four elements of
      decision-making sequences: (i) broaching decision making; (ii) putting forward a
      course of action; (iii) committing or not (to the action put forward); and (iv)
      HCPs' responses to patients' resistance or withholding of commitment. Patients
      have limited opportunities to influence decision making. HCPs' practices may
      constrain or encourage this participation. CONCLUSIONS: Patients, companions and
      HCPs together treat and undertake decision making as shared, though to varying
      degrees. Even for non-negotiable treatment trajectories, the spirit of SDM can be
      invoked through practices that encourage participation (eg by bringing the
      patient towards shared understanding of the decision's rationale).

PMID- 28520203
TI  - Subthalamic nucleus deep brain stimulation for Parkinson's disease in a patient
      with severe haemophilia A.

PMID- 28520204
TI  - Weekly recombinant FIX prophylaxis for severe haemophilia B in normal clinical
      practice: data from UKHCDO and Finland.

PMID- 28520205
TI  - SIPPET trial: the answers.

PMID- 28520206
TI  - Time to review the way we estimate access to haemophilia concentrates worldwide.

PMID- 28520207
TI  - Comparison of F13A1 gene mutations in 73 patients treated with recombinant FXIII
      A2.
AB  - INTRODUCTION: Congenital factor XIII (FXIII) deficiency is a rare, autosomal
      recessive bleeding disorder usually caused by mutations in the F13A1 gene that
      produce a severe quantitative (type I) deficiency of the FXIII-A subunit. AIM: To
      determine the genotypes of patients with severe FXIII-A deficiency treated with
      recombinant FXIII-A subunit (rFXIII-A2 ) participating in three international
      efficacy and safety trials. METHODS: We determined the genotypes of 73 patients
      in total; 32 had already undergone genotype analysis and were known to carry
      F13A1 mutations that have been previously reported in the literature. Mutation
      screening was performed in 41 patients with unknown genetic status using direct
      sequencing. RESULTS: In total, 51 distinct mutations in 73 patients were
      identified. Two patients showed a phenotype of severe FXIII-A deficiency, despite
      having heterozygous missense mutations. Two siblings carried a missense mutation
      in the F13A1 gene (p.Ser296Arg) in combination with a novel, probably polymorphic
      variant of the F13B gene (p.Ser654Phe). Molecular modelling of five F13A1 novel
      missense mutations (p.Leu171Phe, p.Glu204Lys, p.Leu276Phe, p.Asp405His and
      p.Gly411Cys) predicted a damaging effect of these mutations on protein structure.
      Although five patients treated with rFXIII-A2 had transient, low-titre, non
      neutralizing anti-rFXIII antibodies, no patients developed FXIII-neutralizing
      antibodies (inhibitors). CONCLUSION: The identified mutations are causally
      implicated in severe FXIII deficiency; however, they do not appear to increase
      the risk of neutralizing antibody development against rFXIII-A2 .

PMID- 28520208
TI  - Coagulation abnormalities and haemostatic surgical outcomes in 142 patients with
      Noonan syndrome.

PMID- 28520209
TI  - Successful perioperative haemostatic management of aortic coarctation in a 5-week
      old infant with severe haemophilia A.

PMID- 28520210
TI  - Biases in the reporting of hepatocellular carcinoma tumor sizes on the liver
      transplant waiting list.
AB  - : We investigated the possibility that patients with hepatocellular carcinoma
      (HCC) listed for liver transplant with tumors just outside stage T2 size criteria
      may be inaccurately reported as just meeting the tumor size criteria for
      transplant. The United Network for Organ Sharing/Standard Transplant Analysis and
      Research database identified 12,958 patients listed for liver transplants with
      HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor.
      A logistic power peak function was fitted to the single-tumor size histogram,
      with the fitted values representing unbiased expected values. The difference
      between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238
      (22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients
      with tumors outside of transplant criteria had their measurements recorded at the
      margins of eligibility. A risk-adjusted Poisson model evaluated the ratio of
      observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences
      among 6,049 transplants. Only 2.0-cm tumors had observed to expected recurrence
      differing from 1 (ratio 0.73, 95% confidence interval 0.57-0.94), indicating a
      27% lower than expected rate of recurrence. CONCLUSION: Higher than expected
      observed tumor counts at the lower transplant criteria margin were corroborated
      by lower than expected HCC recurrence, suggesting that tumor sizes at the margins
      of HCC transplant criteria may be subject to inaccurate reporting. (Hepatology
      2017;66:1144-1150).

PMID- 28520212
TI  - Models for cutaneous wound healing.

PMID- 28520211
TI  - Aging and Parkinson's disease: Different sides of the same coin?
AB  - Despite abundant epidemiological evidence in support of aging as the primary risk
      factor for PD, biological correlates of a connection have been elusive. In this
      article, we address the following question: does aging represent biology
      accurately characterized as pre-PD? We present evidence from our work on midbrain
      dopamine neurons of aging nonhuman primates that demonstrates that markers of
      known correlates of dopamine neuron degeneration in PD, including impaired
      proteasome/lysosome function, oxidative/nitrative damage, and inflammation, all
      increase with advancing age and are exaggerated in the ventral tier substantia
      nigra dopamine neurons most vulnerable to degeneration in PD. Our findings
      support the view that aging-related changes in the dopamine system approach the
      biological threshold for parkinsonism, actively producing a vulnerable pre
      parkinsonian state. (c) 2017 The Authors. Movement Disorders published by Wiley
      Periodicals, Inc. on behalf of International Parkinson and Movement Disorder
      Society.

PMID- 28520213
TI  - The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on
      lipid droplets by evading ubiquitylation.
AB  - : A sequence variation (I148M) in patatin-like phospholipase domain-containing
      protein 3 (PNPLA3) is strongly associated with fatty liver disease, but the
      underlying mechanism remains obscure. In this study, we used knock-in (KI) mice
      (Pnpla3148M/M ) to examine the mechanism responsible for accumulation of
      triglyceride (TG) and PNPLA3 in hepatic lipid droplets (LDs). No differences were
      found between Pnpla3148M/M and Pnpla3+/+ mice in hepatic TG synthesis,
      utilization, or secretion. These results are consistent with TG accumulation in
      the Pnpla3148M/M mice being caused by impaired TG mobilization from LDs. Sucrose
      feeding, which is required to elicit fatty liver in KI mice, led to a much larger
      and more persistent increase in PNPLA3 protein in the KI mice than in wild-type
      (WT) mice. Inhibition of the proteasome (bortezomib), but not macroautophagy (3
      methyladenine), markedly increased PNPLA3 levels in WT mice, coincident with the
      appearance of ubiquitylated forms of the protein. Bortezomib did not increase
      PNPLA3 levels in Pnpla3148M/M mice, and only trace amounts of ubiquitylated
      PNPLA3 were seen in these animals. CONCLUSION: These results are consistent with
      the notion that the 148M variant disrupts ubiquitylation and proteasomal
      degradation of PNPLA3, resulting in accumulation of PNPLA3-148M and impaired
      mobilization of TG from LDs. (Hepatology 2017;66:1111-1124).

PMID- 28520214
TI  - mTORC1 Inhibits NF-kappaB/NFATc1 Signaling and Prevents Osteoclast Precursor
      Differentiation, In Vitro and In Mice.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) is a critical sensor for
      bone homeostasis and bone formation; however, the role of mTORC1 in osteoclast
      development and the underlying mechanisms have not yet been fully established.
      Here, we found that mTORC1 activity declined during osteoclast precursors
      differentiation in vitro and in vivo. We further targeted deletion of Raptor
      (mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively
      inhibit or activate mTORC1 in osteoclast precursors (monocytes/macrophages),
      using LyzM-cre mice. Osteoclastic formation was drastically increased in cultures
      of Raptor deficient bone marrow monocytes/macrophages (BMMs), and Raptor
      deficient mice displayed osteopenia with enhanced osteoclastogenesis. Conversely,
      BMMs lacking Tsc1 exhibited a severe defect in osteoclast-like differentiation
      and absorptive function, both of which were restored following rapamycin
      treatment. Importantly, expression of nuclear factor kappa-light-chain-enhancer
      of activated B cells (NF-kappaB) and nuclear factor of activated T cells,
      cytoplasmic 1 (NFATc1), transcription factors that are essential for osteoclast
      differentiation was negatively regulated by mTORC1 in osteoclast lineages. These
      results provide evidence that mTORC1 plays as a critical role as an osteoclastic
      differentiation-limiting signal and suggest a potential drawback in treating bone
      loss-related diseases with mTOR inhibitors clinically. (c) 2017 American Society
      for Bone and Mineral Research.

PMID- 28520216
TI  - Evaluation of Prediction of Polymorphisms of DNA Repair Genes on the Efficacy of
      Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer: A
      Network Meta-Analysis.
AB  - This network meta-analysis (NMA) was conducted to compare the predictive value of
      14 SNPs in eight DNA repair genes on the efficacy of platinum-based chemotherapy
      in patients with non-small cell lung cancer (NSCLC). These included ERCC1
      (rs11615, rs3212986, rs3212948), XRCC1 (rs25487, rs25489, rs1799782), XPD
      (rs13181, rs1799793), XPG (rs1047768, rs17655), XPA (rs1800975), XRCC3
      (rs861539), APE1 (rs3136820), and RRM1 (rs1042858). The PubMed and Cochrane
      library databases were reviewed from their inception to February 2017 and studies
      which met our inclusion criteria were included in our investigation. This network
      meta-analysis combines direct and indirect evidence to assess the predictive
      value of 14 SNPs in eight DNA repair genes on the efficacy of platinum-based
      chemotherapy in NSCLC. We evaluated the predictive value through the use of the
      odd ratios (OR) and drawing surface under the cumulative ranking curves (SUCRA).
      A total of 26 eligible cohort studies were enrolled in this NMA. The pairwise
      meta-analysis indicated that in terms of overall response ratio (ORR), ERCC1
      (rs11615), XRCC1 (rs25487, rs1799782), and XPD (rs13181) polymorphisms are
      associated with the efficacy of platinum-based chemotherapy in NSCLC. The result
      of this NMA suggests that there is no significant difference in predictive value
      of 8 DNA repair genes on the efficacy of platinum-based chemotherapy in NSCLC
      patients. The rank of SUCRA values of the 14 SNPs in the eight DNA repair genes
      were: XPD (rs1799793)->ERCC1 (rs3212986)->XPA(rs1800975)->ERCC1(rs3212948)
      >XRCC1(rs25487)->XRCC3(rs861539)->APE1(rs3136820)->ERCC1(rs11615)
      >XRCC1(rs1799782)->RRM1(rs1042858)->XPD(rs13181)->XPG (rs1047768)->XPG(rs17655)
      >XRCC1(rs25489). ERCC1(rs11615), XRCC1(rs25487, rs1799782) and XPD(rs13181)
      polymorphisms were better predictors in evaluating the efficacy of platinum-based
      chemotherapy in NSCLC patients. J. Cell. Biochem. 118: 4782-4791, 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28520215
TI  - Aspirin and the risk of cardiovascular events in atherosclerosis patients with
      and without prior ischemic events.
AB  - BACKGROUND: The benefit of aspirin among patients with stable atherosclerosis
      without a prior ischemic event is not well defined. HYPOTHESIS: Aspirin would be
      of benefit in outpatients with atherosclerosis with prior ischemic events, but
      not in those without ischemic events. METHODS: Subjects from the Reduction of
      Atherothrombosis for Continued Health registry were divided according to prior
      ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event
      (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at
      each clinic visit and considered as a time-varying covariate. The primary outcome
      was the first occurrence of cardiovascular death, myocardial infarction, or
      stroke. RESULTS: In the group with a prior ischemic event, aspirin use was
      associated with a marginally lower risk of the primary outcome at a median of 41
      months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P =
      0.06). In the group without a prior ischemic event, aspirin use was not
      associated with a lower risk of the primary outcome at a median of 36 months (HR:
      1.03, 95% CI: 0.73-1.45, P = 0.86). CONCLUSIONS: In this observational analysis
      of outpatients with stable atherosclerosis, aspirin was marginally beneficial
      among patients with a prior ischemic event; however, there was no apparent
      benefit among those with no prior ischemic event.

PMID- 28520218
TI  - Lithium Bond Chemistry in Lithium-Sulfur Batteries.
AB  - The lithium-sulfur (Li-S) battery is a promising high-energy-density storage
      system. The strong anchoring of intermediates is widely accepted to retard the
      shuttle of polysulfides in a working battery. However, the understanding of the
      intrinsic chemistry is still deficient. Inspired by the concept of hydrogen bond,
      herein we focus on the Li bond chemistry in Li-S batteries through sophisticated
      quantum chemical calculations, in combination with 7 Li nuclear magnetic
      resonance (NMR) spectroscopy. Identified as Li bond, the strong dipole-dipole
      interaction between Li polysulfides and Li-S cathode materials originates from
      the electron-rich donors (e.g., pyridinic nitrogen (pN)), and is enhanced by the
      inductive and conjugative effect of scaffold materials with pi-electrons (e.g.,
      graphene). The chemical shift of Li polysulfides in 7 Li NMR spectroscopy, being
      both theoretically predicted and experimentally verified, is suggested to serve
      as a quantitative descriptor of Li bond strength. These theoretical insights were
      further proved by actual electrochemical tests. This work highlights the
      importance of Li bond chemistry in Li-S cell and provides a deep comprehension,
      which is helpful to the cathode materials rational design and practical
      applications of Li-S batteries.

PMID- 28520217
TI  - The gene encoding the inwardly rectifying potassium channel Kir4.1 may be
      involved in sudden infant death syndrome.
AB  - AIM: Disturbances in brain function and development may play a role in sudden
      infant death syndrome (SIDS). This Norwegian study aimed to test the hypothesis
      that specific variants of genes involved in water transport and potassium
      homeostasis would be predisposing factors for SIDS. METHODS: Genetic variation in
      the genes encoding aquaporin-4 (AQP4), Kir4.1 (KCNJ10) and alpha-syntrophin was
      analysed in 171 SIDS cases (62.6% male) with a median age of 15.5 (2-52) weeks
      and 398 adult controls (70.6% male) with a median age of 44 (11-91) years. All
      the subjects were Caucasians who were autopsied from 1988 to 2013. RESULTS: The
      CC genotype of rs72878794 in the AQP4 gene and a combination of the CC genotype
      in rs17375748, rs1130183, rs12133079 and rs1186688 in KCNJ10 (4xCC) were found to
      be associated with SIDS. The SIDS cases with the 4xCC SNP combination were
      younger than the SIDS cases with other genotype combinations (p = 0.006).
      CONCLUSION: This study indicates that genetic variations in KCNJ10 and AQP4 may
      be predisposing factors for SIDS. Alterations in the expression of the
      AQP4/Kir4.1 complex can disrupt water and ion homeostasis, which may influence
      brain development and facilitate brain oedema formation This may be especially
      unfavourable during the first weeks of life.

PMID- 28520219
TI  - Plasminogen Activator Inhibitor Type-1 as a Regulator of Fibrosis.
AB  - Fibrosis is known as a frequent and irreversible pathological condition which is
      associated with organ failure. Tissue fibrosis is a central process in a variety
      of chronic progressive diseases such as diabetes, hypertension, and persistent
      inflammation. This state could contribute to chronic injury and the initiation of
      tissue repair. Fibrotic disorders represent abnormal wound healing with defective
      matrix turnover and clearance that lead to excessive accumulation of
      extracellular matrix components. A variety of identified growth factors,
      cytokines, and persistently activated myofibroblasts have critical roles in the
      pathogenesis of fibrosis. Irrespective of etiology, the transforming growth
      factor-beta pathway is the major driver of fibrotic response. Plasminogen
      activator inhibitor-1 (PAI-1) is a crucial downstream target of this pathway.
      Transforming growth factor-beta positively regulates PAI-1 gene expression via
      two main pathways including Smad-mediated canonical and non-canonical pathways.
      Overexpression of PAI-1 reduces extracellular matrix degradation via perturbing
      the plasminogen activation system. Indeed, elevated PAI-1 levels inhibit
      proteolytic activity of tissue plasminogen activator and urokinase plasminogen
      activator which could contribute to a variety of inflammatory elements in the
      injury site and to excessive matrix deposition. This review summarizes the
      current knowledge of critical pathways that regulate PAI-1 gene expression and
      suggests effective approaches for the treatment of fibrotic disease. J. Cell.
      Biochem. 119: 17-27, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 28520220
TI  - Endothelial damage effects of circulating microparticles from patients with
      stable angina are reduced by aspirin through ERK/p38 MAPKs pathways.
AB  - INTRODUCTION: Platelet activation participates in the development of both
      coronary artery disease (CAD) and circulating microparticles (MPs). As a commonly
      used medicine for coronary heart disease, whether aspirin affects the function of
      MPs remains unclear. AIMS: This study was designed to test MPs from healthy
      subjects, and stable angina (SA) patients before and after aspirin administration
      were obtained. MPs origins were tested by flow cytometry. Rat thoracic aortas
      were incubated with MPs (with or without aspirin) to determine the effects of MPs
      on expression of ERK1/2, JNKs, and p38 MAPK. Affect on levels of NF-kappaB, VCAM
      1, NO, and O2-. RESULTS: Compared with healthy subjects, MPs concentrations
      increased in SA patients, but decreased after aspirin administration. According
      to flow cytometry, aspirin mainly decreased platelet-derived MP. MPs from SA
      patients decreased the expression of ERK1/2, increased expression of p38 MAPKs,
      JNKs. Increased NF-kappaB, VCAM-1, and (O2-) levels decreased NO content. Aspirin
      therapy significantly inhibited function of MPs from SA patients, and pathway
      inhibitors (ERK1/2 inhibitor PD98059, p38 MAPKs inhibitor SB203580, NF-kB
      inhibitor PDTC) show similar effects with aspirin. CONCLUSION: These results
      indicate that the pro-inflammatory, oxidative stress, procoagulant, and adhesion
      properties of MPs can be partly blocked by aspirin via the ERK-NO/O2- and p38 -NF
      kappaB-VCAM-1 signal pathway, which clarified other functions beyond anti
      atherothrombotic of aspirin.

PMID- 28520223
TI  - Evolution of infectious disease: A biocultural analysis of AIDS.
AB  - The evolution of infectious disease can be understood from an ecological model
      that incorporates information from anthropology, epidemiology, and biomedicine.
      This model considers variables such as the pathogen, the host population, and the
      environment. In this model, the role that culture as well as other environmental
      variables plays in the transmission of infectious disease in human populations is
      considered. In addition, the sociocultural response and its impact on the disease
      process can be analyzed. The present AIDS epidemic is placed in an ecological and
      evolutionary context of the disease in hominid evolution. The interaction between
      Human Immunodeficiency Virus (HIV) and human populations is considered in this
      perspective. The ability of the virus to survive in semen and blood both
      increases as well as limits the possibility of transmission. Cultural practices
      that increase the transmission of blood and semen or increase sexual activity
      will obviously increase the potential risk of viral transmission. In societies
      that practice exchange of blood, blood transfusion, and where vaccinations with
      unclean needles exist or where there is intravenous (IV) drug use, the
      transmission of HIV by blood is enhanced. HIV which can cause a breakdown of the
      immunological system is paradoxically a very fragile pathogen. Replication occurs
      within T-cells, an important part of the immunological system. Outside of the
      blood or semen the virus dies quickly. From the perspective of the pathogen's
      adaptation, the virus has effectively solved the problem of survival. The fragile
      virus's long incubation period and its ability to survive in the presence of
      antibodies help to assure its transmission. HIV's ability to suppress the
      immunological system may assure its immediate survival, but this adaptation may
      cause the death of its host from other opportunistic pathogens that are usually
      not lethal.

PMID- 28520222
TI  - High prevalence of human T-lymphotropic virus type I infection in isolated
      populations of the Western Pacific region confirmed by Western immunoblot.
AB  - High prevalences of antibodies against human T-lymphotropic virus type I (HTLV
      I), as confirmed by Western immunoblot, were found in several remote indigenous
      populations of the Solomon Islands and Vanuatu and in some isolated populations
      of New Guinea that had no contact with Japanese or Africans and little contact
      with Caucasians prior to our bleedings. By contrast, zero or very low prevalences
      of HTLV-I infection were found in Guamanians and Carolinians, despite more than
      30 years of intense contact with the Japanese. A total of 1,601 sera, collected
      between 1963 and 1981 from 21 population groups in the Western Pacific, was
      tested by enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to HTLV-I.
      By ELISA, prevalences of antibodies against HTLV-I ranged from zero to 50%.
      Seropositivity could be confirmed in only 12.5% of 48 ELISA-positive sera
      selected for testing by Western immunoblot. However, the confirmed HTLV-I
      seroprevalences in some Melanesian populations were still as high as those found
      in HTLV-I-endemic regions, such as southwestern Japan and the Caribbean basin.
      HTLV-I prevalences were similar among males and females, and acquisition of
      antibodies increased with age. Our data indicate that infections with HTLV-I or a
      related retrovirus have been widespread in the southwestern Pacific for over 25
      year in populations with minimal outside contact, while some populations which
      had extensive Japanese contact have no evidence of infection. Furthermore, based
      on the high frequency of indeterminate Western immunoblots, we conclude that in
      Melanesia this may represent either incomplete specific reactivity to HTLV-I or
      the existence of an antigenic variant of HTLV-I, distinct from prototype
      Japanese, American, and European HTLV-I strains.

PMID- 28520224
TI  - Environmental context, social interactions, and the spread of HIV.
AB  - The spread of HIV through a population is influenced by many factors. These
      include the frequency and type of sexual activity, age distribution of the
      population, use of intravenous drugs and behaviors associated with their use, the
      pattern of infectivity of the virus during the several stages of the infection,
      geographic location, and the patterns of interaction among individuals and the
      context in which those interactions occur. A number of questions about the
      natural history and epidemiology of AIDS remain unanswered. Since the disease has
      only recently been recognized, historical data are unavailable to aid in
      answering these questions. Mathematical models provide one approach that can be
      of use in understanding the spread of the disease. Because of the complexity of
      the biology and epidemiology of AIDS, useful models must focus on specific
      aspects of the disease. In addition to a brief review of existing models for the
      spread of AIDS, a new model which incorporates the effects of social context
      operating at the time of a sexual encounter is described. The model considers the
      spread of the disease in a population of homosexual men divided into groups based
      on relative risk for the disease. Individuals are assigned to a specific group on
      the basis of their normal sexual activities, but they may take on the
      characteristics of a different risk group temporarily given the conditions
      operating when they engage in a sexual encounter. Results from preliminary
      analyses of the new model indicate that the major effects of incorporating social
      context include a decrease in the number of cases of the disease, sometimes by an
      order of magnitude or more, delayed spread of the disease, and a decreased impact
      of the disease on low and medium risk groups.

PMID- 28520225
TI  - Human T-lymphotropic virus type I: A retrovirus causing chronic myeloneuropathies
      in tropical and temperate climates.
AB  - Human T-cell lymphotropic virus type I (HTLV-I), the first human retrovirus to be
      isolated, is the cause of endemic tropical spastic paraparesis (TSP). Originally,
      this chronic neurological disorder was described as a disease seen among blacks
      of low socioeconomic status living in tropical countries, and thus for many
      decades TSP remained a little known curiosity outside the endemic regions. The
      link between HTLV-I infection and TSP was made fortuitously, when antibodies to
      HTLV-I were found in serum and cerebrospinal fluid of TSP patients in Jamaica,
      Colombia, and Martinique. Soon thereafter a similar disorder, designated HTLV-I
      associated myelopathy (HAM), was reported from southern Japan. This broadened the
      geographic and ethnic boundaries of this chronic myelopathy and the disease has
      now been reported in multiple ethnic groups from more than 40 countries, in both
      tropical and temperate regions. The name TSP/HAM is now used to include all
      patients (regardless of race or country of origin) who have HTLV-I-positive
      endemic TSP or HAM.

PMID- 28520226
TI  - Raymond Pearl memorial lecture, 1989: Cultural practices as determinants of
      clinical pathology and epidemiology of venereal infections: Implications for
      predictions about the AIDS epidemic.
AB  - Sexually transmitted diseases newly introduced into diverse primitive and
      isolated populations have behaved differently in clinical severity and
      seriousness of the epidemics they have caused, because of culturally different
      sexual practices. Epidemic interstitial plasma cell pneumonia in the 1930s-1950s
      in eastern and northern Europe, caused by Pneumocystis carinii and accompanied by
      cytomegalovirus infection, was an unexpected AIDS-like epidemic which spread
      slowly, then quickly and inexplicably disappeared. Newly recognized endemic HTLV
      I and epidemic HIV human retrovirus infections are behaving in a fashion
      similarly difficult to anticipate and predict.

PMID- 28520221
TI  - Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During
      Skeletal Development.
AB  - Recent identification and isolation of suture stem cells capable of long-term
      self-renewal, clonal expanding, and differentiating demonstrate their essential
      role in calvarial bone development, homeostasis, and injury repair. These bona
      fide stem cells express a high level of Axin2 and are able to mediate bone
      regeneration and repair in a cell autonomous fashion. The importance of Axin2 is
      further demonstrated by its genetic inactivation in mice causing skeletal
      deformities resembling craniosynostosis in humans. The fate determination and
      subsequent differentiation of Axin2+ stem cells are highly orchestrated by a
      variety of evolutionary conserved signaling pathways including Wnt, FGF, and BMP.
      These signals are often antagonistic of each other and possess differential
      effects on osteogenic and chondrogenic cell types. However, the mechanisms
      underlying the interplay of these signaling transductions remain largely elusive.
      Here we identify Rap1b acting downstream of Axin2 as a signaling interrogator for
      FGF and BMP. Genetic analysis reveals that Rap1b is essential for development of
      craniofacial and body skeletons. Axin2 regulates Rap1b through modulation of
      canonical BMP signaling. The BMP-mediated activation of Rap1b promotes
      chondrogenic fate and chondrogenesis. Furthermore, by inhibiting MAPK signaling,
      Rap1b mediates the antagonizing effect of BMP on FGF to repress osteoblast
      differentiation. Disruption of Rap1b in mice not only enhances osteoblast
      differentiation but also impairs chondrocyte differentiation during
      intramembranous and endochondral ossifications, respectively, leading to severe
      defects in craniofacial and body skeletons. Our findings reveal a dual role of
      Rap1b in development of the skeletogenic cell types. Rap1b is critical for
      balancing the signaling effects of BMP and FGF during skeletal development and
      disease. (c) 2017 American Society for Bone and Mineral Research.

PMID- 28520227
TI  - AIDS in Africa: A bioanthropological perspective.
AB  - The epidemiological characteristics of acquired immunodeficiency syndrome (AIDS)
      in Africa are reviewed. Infection rates with human immunodeficiency virus 1 (HIV
      1) and human immunodeficiency virus 2 (HIV-2) vary across the continent of Africa
      with the highest infection rates occurring in East and Central Africa. The
      primary pattern of infection with HIV-1 is characterized by high rates of
      heterosexual vs. homosexual transmission, a low male to female sex ratio of
      cases, and high rates of pediatric AIDS. Cultural anthropologists have emphasized
      variation in human sexual behavior as an important factor in understanding the
      HIV epidemic. These studies have focussed on understanding the range of sexual
      risk behaviors present in different cultures and the cultural meanings of these
      behaviors. Biological anthropologists approach the study of human disease with an
      interest in human biological variation, evolutionary models, and the interface
      between biology and behavior. A Bioanthropology Research Agenda for AIDS is
      proposed which focuses on these three areas. Potential research domains for
      biological anthropologists include: human biological variation and cofactors of
      infection and disease, the evolutionary impact of HIV infection, and the
      interface between biology and behavior and the biological impact of behavior.
      Working with colleagues in other disciplines, biological anthropologists can
      assist in furthering understanding of the variables of HIV infection and disease.

PMID- 28520228
TI  - Introduction: Biocultural implications of AIDS and other retroviral disorders.

PMID- 28520229
TI  - Epidemiology and clinical picture of human immunodeficiency virus type 1
      infection and the acquired immune deficiency syndrome.
AB  - Human Immunodeficiency Virus Type 1 (HIV-1) infection which causes the terminal
      Acquired Immune Deficiency Syndrome (AIDS) is one of the major new pandemics of
      this millenium. This infection is believed to be a zoonosis which achieved
      sustained transmission among humans because of recent increases in sexual
      promiscuity and needle-sharing drug use. Although the HIV-1 epidemic is of
      relatively recent onset, its modes of transmission have been clearly defined:
      sexual relations, blood injection, and childbirth. Other possible transmission
      methods such as non-sexual social interaction and insects have been explicitly
      excluded. Susceptibility is increased by genital ulcers and lack of male
      circumcision but probably not by genetic factors or female circumcision.
      Transmissibility is also increased by genital ulcers and, more importantly, by
      the stage of disease. Progression by stages to fatal diseases will probably occur
      in most, if not all, infected individuals, usually within a decade. While HIV-1
      has a direct effect on the intestinal track and the central nervous system, its
      primary effect is suppression of the immune system resulting in overwhelming
      secondary infections and, less clearly, cancers. Human Immunodeficiency Virus
      Type 1 infection is incurable and is likely to remain so for the foreseeable
      future. Although life-prolonging treatments have been developed, a vaccine will
      likely not be available in the foreseeable future. Like most previous new
      epidemic diseases, HIV-1 infection is being and will continue to be modified by
      changing human behavior patterns.

PMID- 28520230
TI  - Perspective: Human immunodeficiency virus infection in children.
AB  - Epidemiologic studies indicate that the number of women and children with human
      immunodeficiency virus (HIV) infection will continue to increase in the next
      decade. The impact of this aspect of the AIDS pandemic, including increased
      infant mortality, will be greatest in developing nations. The biologic properties
      of HIV, a lentivirus, complicate the strategies to alter the course of the
      pandemic. A long asymptomatic interval between initial infection and the onset of
      clinical disease, the ability of HIV to evade immune clearance, and the
      propensity for rapid mutation and selection of viral variants all favor survival
      of the virus over the host.

PMID- 28520231
TI  - Lymphocyte alloantigenic challenge as a potential cofactor in HIV infection and
      progression to AIDS.
AB  - A hypothesis is developed that circulatory exposure to alloantigens found on
      lymphocytes triggers a series of events leading to suppression of the cell
      mediated arm of the immune system and, therefore, that such alloantigenic
      challenge can be an important cofactor promoting infection with the human
      immunodeficiency virus (HIV) and development of the acquired immunodeficiency
      syndrome (AIDS) following infection. The explanatory model that is developed is
      based in large part on current knowledge of the results of fetal lymphocyte
      alloantigenic challenge of the maternal immune system. It is our contention that
      the maternal response which leads to suppression of cell-mediated immunity is a
      mechanism promoting survival of the fetal "allograft," and that this mechanism is
      an evolutionary adaptation in humans and other placental mammals. We also
      hypothesize that circulatory exposure to these same alloantigens leads to an
      immunosuppressive state which enhances survival of HIV in an exposed individual
      and augments the immunosuppressive action of HIV in promoting progression to
      clinical AIDS. Findings from studies of individuals who are at risk for exposure
      to lymphocyte alloantigenic challenge and from HIV infected patients are reviewed
      and discussed in light of this hypothesis.

PMID- 28520232
TI  - Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the
      Cleavage of Caspases.
AB  - Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced
      pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs.
      However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear.
      We established an iPSC-MSC-transplanted host versus graft reaction mouse model
      using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17
      phenotypes and their cytokines were investigated in vivo and in vitro. The role
      of caspases and the soluble factors involved in the effects of MSCs were
      examined. We found that iPSC-MSC grafts led to more cell survival and less
      infiltration of inflammatory cells in mice. iPSC-MSC transplantation inhibited T
      cell proliferation, decreased Th1 and Th2 phenotypes and cytokines, upregulated
      Th17 and Treg subsets. Moreover, iPSC-MSCs inhibited the cleavage of caspases 3
      and 8 and inhibition of caspases downregulated Th1, Th2 responses and upregulated
      Th17, Treg responses. Soluble factors were determined using protein array and TGF
      beta1/2/3, IL-10, and MCP-1 were found to be highly expressed in iPSC-MSCs. The
      administration of the soluble factors decreased Th1/2 response, upregulated Treg
      response and inhibited the cleavage of caspases. Our results demonstrate that
      iPSC-MSCs regulate T cell responses as a result of a combined action of the above
      soluble factors secreted by iPSC-MSCs. These factors suppress T cell responses by
      inhibiting the cleavage of caspases. These data provide a novel immunomodulatory
      mechanism for the underlying iPSC-MSC-based immunomodulatory effects on T cell
      responses. Stem Cells 2017;35:1719-1732.

PMID- 28520235
TI  - First Principles Neural Network Potentials for Reactive Simulations of Large
      Molecular and Condensed Systems.
AB  - Modern simulation techniques have reached a level of maturity which allows a wide
      range of problems in chemistry and materials science to be addressed.
      Unfortunately, the application of first principles methods with predictive power
      is still limited to rather small systems, and despite the rapid evolution of
      computer hardware no fundamental change in this situation can be expected.
      Consequently, the development of more efficient but equally reliable atomistic
      potentials to reach an atomic level understanding of complex systems has received
      considerable attention in recent years. A promising new development has been the
      introduction of machine learning (ML) methods to describe the atomic
      interactions. Once trained with electronic structure data, ML potentials can
      accelerate computer simulations by several orders of magnitude, while preserving
      quantum mechanical accuracy. This Review considers the methodology of an
      important class of ML potentials that employs artificial neural networks.

PMID- 28520234
TI  - Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors: A report of
      five cases.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disorder. Recently, BP
      induced by dipeptidyl peptidase-4 (DPP-4) inhibitors has been a concern. Although
      DPP-4 inhibitors are commonly used in the Asian population because of their
      safety and efficacy, BP associated with DPP-4 inhibitors is sometimes seen in
      clinical settings. Here, we report five Japanese cases of BP associated with the
      agents. In the present cases, BP occurred in older adults using four different
      DPP-4 inhibitors, which showed various clinical manifestations in terms of
      latency period for BP, sex, glycemic control and diabetes duration. Withdrawal of
      DPP-4 inhibitors was effective in improving BP, and achieved remission even in
      cases requiring oral steroid administration and intravenous immunoglobulin
      therapy. Clinicians should note the importance of early diagnosis of this
      clinical condition and initiate prompt withdrawal of DPP-4 inhibitors.

PMID- 28520233
TI  - A Nanojunction Polymer Photoelectrode for Efficient Charge Transport and
      Separation.
AB  - A metal-free photoanode nanojunction architecture, composed of B-doped carbon
      nitride nanolayer and bulk carbon nitride, was fabricated by a one-step approach.
      This type of nanojunction (s-BCN) overcomes a few intrinsic drawbacks of carbon
      nitride film (severe bulk charge recombination and slow charge transfer). The top
      layer of the nanojunction has a depth of ca. 100 nm and the bottom layer is ca.
      900 nm. The nanojunction photoanode results into a 10-fold higher photocurrent
      than bulk graphitic carbon nitride (G-CN) photoanode, with a record photocurrent
      density of 103.2 MUA cm-2 at 1.23 V vs. RHE under one sun irradiation and an
      extremely high incident photon-to-current efficiency (IPCE) of ca. 10 % at 400
      nm. Electrochemical impedance spectroscopy, Mott-Schottky plots, and intensity
      modulated photocurrent spectroscopy show that such enhancement is mainly due to
      the mitigated deep trap states, a more than 10 times faster charge transfer rate
      and nearly three times higher conductivity due to the nanojunction architecture.

PMID- 28520236
TI  - Analysis of amino acids using serially coupled columns.
AB  - Single conventional columns in reversed-phase liquid chromatography are
      insufficient for analysing the isoindoles of primary amino acids due to their
      limited functionality. An interesting possibility for increasing the separation
      power is the combination of several columns of different nature, where the length
      is modified by coupling small segments. This approach may require a considerable
      investment to have multiple lengths for each stationary phase. However, the
      combination of only two columns of fixed length can be enough to resolve
      satisfactorily relatively complex mixtures, provided that an optimised gradient
      program is applied. In this work, a mixture of 19 primary amino acid isoindoles
      found in proteins was analysed. Four stationary phases were assayed: C18,
      pentafluorophenyl-C18, C4 and cyano. The mixture of isoindoles was successfully
      resolved in practical times using a pentafluorophenyl-C18 column coupled to a C4
      column, in spite of the extremely poor performance obtained when each column is
      used isolatedly, independently of the length. The extreme diversity in the
      polarities of the isoindoles and the need of extrapolating the retention
      behaviour in certain regions of the solvent content domain makes the modelling of
      the retention behaviour of the isoindoles particularly difficult. Nevertheless,
      the predicted optimal separations were very satisfactory.

PMID- 28520237
TI  - Phylogenies and the forces of evolution.
AB  - The construction of phylogenetic trees from gene frequency data assumes that a
      history of binary fissioning of populations has been the major cause of genetic
      variation. However, in many areas of the world human populations have been
      relatively stable with local gene flow. This population history is closer to an
      isolation by distance model. It was modelled by a simulation of gene frequency
      changes in a linear sequence of 50 stable populations with gene flow among
      neighboring populations. Phylogenetic trees were constructed from the gene
      frequencies after the simulation was run for 500 generations. Using only a few
      loci there is little correlation between genetic and geographic distance, but
      with 40 or more loci, there was a perfect correlation with geographic distance. A
      different population model can thus result in a phylogenetic tree comparable to
      those assumed to be produced by binary fission.

PMID- 28520238
TI  - Biological variability in a migrating isolate, the Tokelau Islands: Child growth
      in different environments.
AB  - The magnitude and rates of growth have been compared among two cross-sectional
      samples of Tokelau children on the basis of 26 anthropometric dimensions. One of
      the samples consisted of children living on the Tokelau Islands. The migrant
      sample consisted of children of Tokelau descent who were living in New Zealand.
      The comparison between samples suggest significant differences in the rate of
      linear growth at the younger ages. However, most differences were not significant
      among 17 year olds. The results support the hypothesis that even when the
      original environment is favorable, qualitative changes in the environment may
      affect the general pattern of growth. The effects of an accelerated growth
      pattern cannot be determined at this time.

PMID- 28520239
TI  - Relationship between population density and rates of injury mortality in New York
      State (exclusive of New York City), 1978-1982.
AB  - The relationship between population density and rates of mortality from
      unintentional and intentional injuries is examined using mortality data from New
      York State (exclusive of New York City), 1978-1982. Records for 26,118
      individuals with an underlying cause of death due to injury were assigned to
      population density quintiles based on residence of decedent at time of death.
      Mortality rates for each population density quintile were examined separately by
      sex and for 11 causes of injury death. Overall, injury mortality is highest in
      the most rural and most urban populations. For both sexes, there is an inverse
      relationship between mortality from motor vehicle incidents and population
      density, and a positive relationship between homicide and population density.
      Male mortality from unintentional poisoning deaths shows a positive relationship
      with population density. Male mortality from fires shows a U-shaped relatinship
      with population density, with the highest mortality in the most rural and most
      urban populations. The relationships observed here between injury mortality and
      population density are most likely due to concomitant variation with aspects of
      the physical and cultural environments, such as socioeconomic status, ethnicity,
      and individual risk behaviors.

PMID- 28520240
TI  - The effect of height on family income.
AB  - The effect of height on earnings of adult males sampled in the second National
      Health and Nutrition Examination Survey, 1976-1980, was examined. Data were
      collected using the multistage probability sampling method. Information was
      available on medical history, physical examination, anthropometric dimensions,
      diet, and sociodemographic characteristics. Complete information was available on
      4,563 males, aged 20-65 years. The correlation between family income and height
      was low (r = 0.13, P = 0.001). There was a secular trend for increasing mean
      height over time, so that younger individuals were taller than older ones even
      after correction for the decrease in stature caused by aging. After stratifying
      by age and race, education and marital status, but not height, were significantly
      associated with total family income. The weight-height ratio was significantly
      related to income of Whites but not of nonwhites. White males in the highest
      income category were significantly taller, heavier, more adipose, had higher
      levels of education, and were more often married than were their lowest income
      white counterparts. Among nonwhites, marital status and education alone
      differentiated highest from lowest income nonwhite males. Thus, at least for
      White males, appearance, that is, adiposity, together with education and marital
      status, are major factors relating to income.

PMID- 28520242
TI  - Brief Review.

PMID- 28520241
TI  - The reliability of recalled estimates of menarcheal age in a sample of older
      women.
AB  - The accuracy of recalled age at first menses has been questioned, particularly if
      subjects are relatively old. This paper illustrates the use of a statistical
      technique that quantifies the reliability of recalled age at menarche based on re
      interview of a small (15-20) subsample of subjects. Menarcheal age collected with
      the retrospective method in a sample of 108 females, 50 years of age and older,
      from Limon, Costa Rica, is reliable.

PMID- 28520243
TI  - Infertility in Herero pastoralists of southern Africa.
AB  - Transition from low to high rates of fertility among Herero pastoralists of the
      northern Kalahari of Botswana is examined. Total fertility rates have increased
      from 2.65 in the first half of this century to 7.02 in the last decade, while
      postreproductive women report having had only 3.47 births. We use an indirect
      estimator of the fertility of mothers to show that the Herero have been afflicted
      with abnormally low fertility since early in this century. Although the several
      possible causes of subfertility in this population, including disease, maternal
      health, and child care practices are examined, it is concluded that the effects
      of venereal diseases are most likely responsible for abnormally low fertility.
      The dramatic increase in fertility following treatment of a major cause of
      infertility underscores the potential impact diseases may have on human
      reproductive patterns. This study is the first to document subfertility in an
      ethnic group of southern Africa.

PMID- 28520244
TI  - Longitudinal principal components analysis of patterns and predictors of growth
      in Guatemalan children.
AB  - Longitudinal principal components (LPC) analysis was used to assess growth
      patterns in children from rural Guatemala in order to determine if this
      methodology could provide additional information regarding correlates of growth
      compared to more traditionally used methods based on attained size and
      increments. LPC analysis reduces measures at many points in time into a few
      parameters. However, LPC analysis requires complete data, and many cases may be
      lost due to missing values. Thus the potentially greater sensitivity of LPC
      analysis should be weighed against the reduced power resulting from smaller
      sample sizes. Component indices representing centile level and centile shift,
      attained size, and 3 to 36 month increments of growth in length and weight were
      used as the dependent variables in multiple regression models in order to examine
      the effects of environmental variables, such as home dietary intake,
      supplementation, and prevalence of diarrhea on growth. Regardless of which growth
      index, i.e., attained size, incremental change, or principal component, was used,
      regression results were similar; higher nutritional intakes were generally
      associated with greater and more rapid growth from birth to age 3 years. The
      possible advantages of LPC analysis over more traditional methods were not great;
      therefore, LPC analysis is not recommended as the method of choice in this
      population.

PMID- 28520245
TI  - Skin reflectance of children and young adults of Aymara ancestry.
AB  - The skin reflectance of 556 Andean Indians of Aymara ancestry (305 males, 251
      females; 10.0-29.9 yr) residing in La Paz, Bolivia (average altitude of about
      3,600 m) is described. Reflectances were measured at three wavelengths (425 nm,
      545 nm, and 685 nm) on two different sites, the medial surface of the upper arm
      and forehead. Males tended to be significantly darker than females on both the
      upper arm and forehead (P < .05). Female Aymara tended to lighten significantly
      in skin color with age on both the upper arm and forehead, while males tended to
      lighten significantly with age only on the upper arm (P < .05). The results of
      comparisons between three categories based on paternal and maternal surnames (two
      Aymara surnames, one Aymara and one Spanish surname, and two Spanish surnames)
      were consistent with the hypothesis that the possession of Spanish surnames is
      positively related to the degree of European admixture in urban Aymara. However,
      the extent of admixture within each surname category may differ between rural and
      urban Aymara, making classification by surnames problematic for rural-urban
      comparisons.

PMID- 28520246
TI  - Breif Reviews.

PMID- 28520247
TI  - Skin and subcutaneous adipose tissue weights in older Japanese determined by
      cadaver dissection.
AB  - Forty-six embalmed cadavers of elderly Japanese 48 to 95 years of age, 35 males
      and 10 females, were completely dissected, and the weights of skin and
      subcutaneous adipose tissue were determined. Absolute and relative skin weight in
      males (2.68 kg, 5.7%) were similar to those in females (2.73 kg, 6.1%). However,
      females had more dissectible subcutaneous adipose tissue (5.82 kg, 12.3%) than
      males (3.18 kg, 6.3%). These figures are comparable to dissection data obtained
      from embalmed cadavers in Belgium which covered a similar age range. There were
      statistically significant differences between Japanese and Belgians for body
      weight and skin weight. However, there was no difference in relative skin weight.
      Similar sex differences were apparent in the Japanese and Belgians. Skin and
      subcutaneous adipose tissue weights were significantly correlated with body
      weight in both sexes. Prediction equations for skin weight (SW) and subcutaneous
      adipose tissue weight (SATW) from body weight in Japanese are SW (g) = 0.04357
      Body weight + 638.3 (r = 0.70; SEE = 386.7 g) (for males and females); SATW (g) =
      0.18902 Body weight - 5837.4 (r = 0.78; SEE = 1,328.3 g) (for males); and SATW
      (g) = 0.36497 Body weight - 10581.5 (r = 0.79; SEE = 2,560.1 g) (for females).

PMID- 28520248
TI  - Genetics, ethnohistory, and linguistics of Brac, Yugoslavia.
AB  - Serogenetic data involving 21 genetic systems were collected from 12 villages on
      the island of Brac (Yugoslavia) in 1987. Maximum sample size was 709 individuals.
      The UPGMA dendrogram based on genetic distances was readily interpretable within
      the contexts of village settlement history, social relationships, and sample size
      considerations. The gene diversity value (H = 0.3029 +/- 0.0119) was both quite
      high and extremely similar to the average heterozygosity value on the neighboring
      Peljesac peninsula. Quadratic assignment procedures were used to investigate
      genetic-linguistic-geographic correspondences. Unlike the Peljesac peninsula,
      where the distance matrix correlations between genetics and linguistics, genetics
      and geography, and linguistics and geography were all positive and highly
      statistically significant; on Brac, only the linguistics-geography correlation
      achieved statistical significance. Reasons for the differences are sought in the
      different migrational characteristics of these two population systems, in the
      complex interaction between evolutionary forces promoting population
      differentiation (genetic drift) and homogeneity (gene flow), and in known
      patterns of sociocultural interaction that might have skewed the genetic
      geographic associations on Brac.

PMID- 28520249
TI  - Validity of skinfold and girth based regression equations for the prediction of
      body composition in obese adults.
AB  - The validity of generalized and obese population-specific body composition
      prediction equations for estimating percent fat was examined. Thirty-eight
      clinically obese women (mean +/- SD, % fat = 46.4 +/- 5.2%, body mass = 97.2 +/-
      17.7 kg, age = 41.8 +/- 13.3 years) and 16 clinically obese men (% fat = 39.2 +/-
      3.8%, body mass = 126.7 +/- 24.6 kg, age = 43.0 +/- 11.6 years) had % body fat
      estimated by hydrostatic weighing (with RV measured) and had a series of skinfold
      and girth-based prediction equations applied to estimate % fat. The equations
      were chosen because they were said to be "generalized" or because they were
      "population specific" to obese samples of subjects. Results of the present study
      indicated that the majority of prediction equations were not valid estimators of
      % body fat in obese males and females. Of the equations that were valid
      estimators of % body fat (mean differences in % fat of < 3%, r >= 0.70, SE < 5%),
      all but one (Lohman, 1981) utilized girths as part of the prediction technique.
      It was concluded that generalized girth-based equations could be utilized for
      prediction of % body fat in obese subjects.

PMID- 28520250
TI  - The relationship of body fat distribution to non-insulin-dependent diabetes
      mellitus in a Navajo community.
AB  - The relationship between non-insulin-dependent diabetes mellitus (NIDDM) and body
      fat distribution (BFD) as measured by waist/hip circumference (WHR) was
      investigated in a Navajo community. A sample of 136 females and 89 males, 20
      years and older, was recruited using a cluster-sampling design. Fifty percent of
      the females and 30.3% of the males are overweight [body mass index (BMI)
      equivalent of >120% ideal body weight]. Prevalence of NIDDM is 14% in females and
      10.1% in males. The sample is characterized by central BFD (mean WHR=0.897+/
      0.075, females and mean WHR=0.963+/-0.071, males). WHR is significantly related
      to age and BMI in males (P < 0.05), but not in females. Adjusted odds ratios for
      risk of NIDDM prevalence with increasing WHR category were estimated from a
      multiple logistic regression model which controlled for age and BMI. The odds
      ratio and 95% confidence interval (95% CI) is 2.19 (1.14, 4.19) for risk of NIDDM
      prevalence for a female in the middle BFD category compared to a female in the
      low BFD category. Risk increases to 3.63 (95% CI=1.25, 10.52) for a female in the
      highest BFD category. Although there is an increased risk of NIDDM prevalence
      with central BFD for males, it is not statistically significant. Preferential
      energy storage in abdominal fat depots may be a phenotypic expression of the
      "Thrifty Genotype," which places American Indians at greater risk for metabolic
      disorders.

PMID- 28520252
TI  - Children's memories for events relating to treatment for eye cancer: Influence of
      age at loss of eye.
AB  - Treatment for retinoblastoma frequently involves removal of at least one eye in
      the first 5 years. Variation in age of treatment leads to the assumption that
      children's later verbal accessibility of early traumatic memories may vary, with
      some children having less opportunity to make sense of their condition. Video
      recordings were made of 17 children who had undergone enucleation either before
      24 months (n = 8) or after 24 months (n = 9) involved in "hospital play'' using
      props designed to elicit talk about "eyes." The hypothesis that a larger number
      of verbalizations about medical procedures would occur in children enucleated
      after 24 months than before 24 months was supported. Children enucleated after 24
      months engaged in significantly more talk about enucleation and/or examination
      under anesthetic whereas none of the children enucleated in infancy talked about
      these medical events. The outcome supports the view that there is a transition
      around 24 months in the extent to which children can have verbal access to
      previous traumatic memories. The design of interventions needs to take into
      account that children enucleated in infancy have less opportunity for later
      verbal access to early memories of traumatic events than those treated later,
      leading to possible misconceptions about their own condition.

PMID- 28520253
TI  - Infants placed in foster care prior to their first birthday: Differences in kin
      and nonkin placements.
AB  - Using data from the National Survey of Child and Adolescent Well-Being, this
      study examines differences between kinship and foster placements for infants
      placed in out-of-home care prior to their first birthday. The differences
      examined include developmental status at time of placement, differences in the
      home and neighborhood environments, and the duration of time in placement.
      Participants included 457 infants placed in either kinship or foster care and
      their caregivers. Findings suggest that infants placed with kin had fewer
      developmental concerns 2 to 6 months after the initial Child Protective Services
      investigation and spent significantly less time in placement. The quality of
      foster and kinship homes and neighborhoods also differed: Foster homes were
      generally of better quality and located in safer neighborhoods. Overall, for both
      kin and foster care, the data suggest that even after passage of the Adoption and
      Safe Families Act of 1997 (ASFA, Public Law 105-89), infants remain in care for a
      long time: Approximately one third of infants are still in out-of-home care 3
      years after the initial investigation.

PMID- 28520251
TI  - Interactive coordination of currently depressed inpatient mothers and their
      infants during the postpartum period.
AB  - In healthy mother-infant dyads, interactions are characterized by a pattern of
      matching and mismatching interactive states with quick reparation of mismatches
      into matches. In contrast, dyads in which mothers have postpartum depression show
      impaired mother-infant interaction patterns over the first few months of the
      infant's life. The majority of studies that have examined such interaction
      patterns have drawn on community samples rather than on depressed inpatient
      samples of mothers who were in a state of current depression at the time of
      assessment. To date, no study has investigated specific microanalytic patterns of
      interactive coordination between depressed German mothers and their infants using
      the Face-to-Face Still-Face paradigm (FFSF). The primary goal of this study was
      to evaluate specific patterns of dyadic coordination and the capacity for
      repairing states of miscoordination in an inpatient sample of postpartum
      currently depressed mothers and their infants as compared with a healthy control
      group. A sample of 28 depressed inpatient German mothers and their infants (age
      range = 1-8 months, M age = 4.06 months) and 34 healthy dyads (range = 1-8
      months, M age = 3.89 months) were videotaped while engaging in the FFSF. A focus
      was placed on the play and reunion episodes. Compared with healthy dyads, dyads
      with depressed mothers showed less coordination of positive matched states and
      longer latencies when repairing interactive mismatching states into positive
      matched states. Clinical implications are discussed.

PMID- 28520254
TI  - The psychology of infant colic: A review of current research.
AB  - Colic, or excessive infant crying, occurs during the first 3 months in
      approximately 15 to 20% of infants and is the most common concern for which
      parents seek medical advice during an infant's first year. Various physiological
      and environmental causes have been investigated. Some researchers have proposed
      multifactorial causes while others have argued that it is simply the extreme end
      of the normal crying continuum. As the etiology of colic is not clear,
      definitions of colic have relied on behavioral descriptions, and the relative
      merits of specific behaviors in affording an accurate definition are debated.
      This lack of clarity has compounded difficulties in identifying effective
      interventions for colic. One point of agreement is that colic is extremely
      distressing for parents. Some have argued that the disruption to the infant
      parent relationship can have long-term implications for development while others
      have argued that only if the crying persists beyond 3 months is there a risk of
      long-term implications. It is concluded that due to the incidence of colic and
      the immediate impact it has on family functioning, more research is required to
      further our understanding of colic. In addition, the identification of effective
      coping strategies and consoling methods to assist parents through this stressful
      period is required.

PMID- 28520256
TI  - Stresses of conquest: A study of Wilson bands and enamel hypoplasias in the Maya
      of Lamanai, Belize.
AB  - This paper examines the prevalence of Wilson bands and hypoplasias in the dental
      enamel of a sample of Postclassic and Historic Maya Indian remains from the
      archaeological site of Lamanai, Belize. Mandibular canines were removed from 23
      individuals from the two periods. The surface of a polished, acid etched,
      longitudinal section of each canine was examined with scanning electron
      microscopy for the presence of enamel malformations. A large number of Wilson
      bands and shallow hypoplasias were identified; however, more severe macroscopic
      hypoplasias were rare. The two kinds of defects were found to be temporally
      associated in only 25-50% of instances, indicating that circumstances leading to
      their formation are likely distinct. The mean number of both Wilson bands and
      shallow hypoplasias was found to be significantly different between samples,
      indicating an increase in developmental stress in the Historic occupation. As
      dietary differences have not been detected between the occupations, the observed
      differences in enamel defect prevalence can be attributed to the effects of
      changing epidemiological patterns following the Spanish conquest.

PMID- 28520257
TI  - Commingling analysis of blood pressure in the Tecumseh community health study.
AB  - A commingling analysis of the distribution of systolic and diastolic blood
      pressure was performed on measurements from 9,226 individuals living in Tecumseh,
      Michigan during 1962-1965. Even after correcting for skewness in the
      distributions, multiple normal distributions fit the data significantly better
      than a single normal one, suggesting some level of commingling. The exact nature
      of the components differed depending on the phenotype, and the number of
      components entertained, suggesting a possibly complex etiology, but with some
      definite qualitative effects. Segregation analysis under the mixed model is
      needed to address the nature of blood pressure in this community more
      definitively.

PMID- 28520255
TI  - Core-Shell and Layer-by-Layer Assembly of 3D DNA Crystals.
AB  - A long-standing goal of DNA nanotechnology has been to assemble 3D crystals to be
      used as molecular scaffolds. The DNA 13-mer, BET66, self-assembles via Crick
      Watson and noncanonical base pairs to form crystals. The crystals contain solvent
      channels that run through them in multiple directions, allowing them to
      accommodate tethered guest molecules. Here, the first example of
      biomacromolecular core-shell crystal growth is described, by showing that these
      crystals can be assembled with two or more discrete layers. This approach leads
      to structurally identical layers on the DNA level, but with each layer
      differentiated based on the presence or absence of conjugated guest molecules.
      The crystal solvent channels also allow layer-specific postcrystallization
      covalent attachment of guest molecules. Through controlling the guest-molecule
      identity, concentration, and layer thickness, this study opens up a new method
      for using DNA to create multifunctional periodic biomaterials with tunable
      optical, chemical, and physical properties.

PMID- 28520258
TI  - Genetic studies of human apolipoproteins: XII. Population genetics of
      apolipoproteins in Papua New Guinea.
AB  - The gene products of the apolipoprotein A-I, A-II, A-IV, C-II, C-III, D, E and H
      loci have been screened by isoelectric focusing followed by immunoblotting from
      two Papua New Guinean populations, the Huli and the Pawaia. Only APO E and APO H
      revealed common polymorphisms. A putative unique A-IV variant has been
      identified, but due to the lack of family data it is not characterized further.
      Three common APO H alleles were observed in both groups with comparable
      frequencies. But significantly different distributions of three APO E alleles
      were noted in the Huli and the Pawaia. The respective frequencies of the APO E*2,
      APO E*3, and APO E*4 alleles were 0.154, 0.356, and 0.490 in the Huli and 0.138,
      0.603, and 0.259 in the Pawaia. A strikingly high frequency of the APO E*4 allele
      in Papua New Guinea may provide a useful insight into the studies of genetic and
      environmental interactions in controlling the cholesterol levels in the general
      population.

PMID- 28520259
TI  - Asymmetry and intraindividual diversity in digital dermatoglyphics of Bulgarians.
AB  - A random sample of 2,130 apparently healthy Bulgarians, 1,065 of each sex, was
      investigated to obtain a detailed picture of finger dermatoglyphic asymmetry and
      intraindividual diversity in the population examined. Both sexes showed an almost
      equal pattern of asymmetry and diversity. Relative pattern asymmetry, taking into
      account the pattern type frequencies, tends to be higher in males, being
      especially pronounced on fingers which show a low asymmetry in other aspects.
      Like other populations so far examined, Bulgarians display higher rates in males
      than in females concerning the total, ulnar, and radial ridge-counts, their
      asymmetries, and intraindividual diversities. However, the more analysis of the
      ridge-count asymmetry is worked out in detail, the more it becomes evident that
      both sexes are asymmetrical not so much to a different degree as in a different
      manner. As a whole, the ambidirectional, directional, fluctuating, and relative
      asymmetries are practically consistent in both sexes. Important sex differences
      are revealed in the structure of the directional and fluctuating asymmetries
      concerning contrasts between their radial and ulnar levels. The sex differences
      in directional asymmetry are discussed in the light of possible effects of the
      sex chromosomes upon the mediolateral developmental gradients. Expressed
      modulation of the fluctuating asymmetry by finger is interpreted as evidence for
      considerable differences between separate finger pairs in their sensitivity to
      stressful factors. Presented results are relevant to anthropology and population
      genetics and could have implications in medical genetics and teratology, serving
      as normative data in pathological conditions.

PMID- 28520261
TI  - Search for secular trends in calvarial diameters, cranial base height, indices,
      and capacity in South African Negro crania.
AB  - Two hundred eighteen South African Negro male crania were arranged in 5-year
      birthdate cohorts from 1880-1884, 1890-1894, up to 1930-1934 inclusive and
      investigated for the presence of a secular trend in their dimensions. Maximum
      breadth, maximum length, basibregmatic height, cranial base height, and bi
      auricular breadth (BAB) were measured, and cranial index (CI), cranial capacity
      (CC), and cranial base height index (CBHI) were determined. Cranial length
      exhibited a significant increase from 1890 to 1930. Cranial base height and CBHI
      exhibited statistically significant declines over the same period. The absence of
      secular trends in the other dimensions studied corresponds to previous analyses
      of the lengths of the femora and tibiae of the same sample. The secular trends in
      cranial length, cranial base height and its index, and the absence of trends in
      the other dimensions, are discussed in relation to an apparent decrease in the
      standard of living occurring in this population after 1900. It is unlikely that
      the absence of a positive secular trend denotes the attainment of a genetically
      determined ceiling to the physical size of the subjects represented by these
      skeletons. It is more likely that the environmental factors believed to produce a
      positive secular trend were absent in the years from which this sample was drawn
      and that signs of improvement in these factors, if any, would be so recent that
      evidence of their effect is not yet available from our cadaver-derived skeletons.

PMID- 28520260
TI  - Selective neutrality of surname, distribution in an immigrant indian community of
      Houston, Texas.
AB  - From survey data on surnames in an immigrant community of Indians in Houston,
      Texas, it is shown that the family size distribution and the distribution of the
      number of male children per family are independent of the surnames of the
      parents. This provides a direct test of selective neutrality of surname
      distributions. A genetic theory of sampling distribution of neutral alleles is
      employed to estimate the parameter of the surname distribution, and analytical
      results for the expectation and variance of the frequencies of surnames with a
      different number of copies in a sample are provided. It is also shown that the
      surname distribution may indicate presence of mixture in a sample, which can be
      examined by such theoretical approaches. The transition of surname distributions
      in two successive generations is shown to follow the pattern predicted by random
      extinction of surnames.

PMID- 28520262
TI  - Variation in body size and shape among South American Indians.
AB  - Available information on mean adult male and female height, weight, sitting
      height, and relative sitting height for 62 groups is used to examine the
      relationship between anthropometric measurements and climate, geographical
      location, and linguistic affiliation among South American Indians. Results of
      correlation analysis indicate that height increases from the north to the south
      of the continent and is significantly negatively correlated with precipitation
      but is not significantly correlated with most measures of temperature. Only in
      females is weight significantly correlated with any of the location or climatic
      variables. Sitting height is correlated with both temperature and precipitation,
      while relative sitting height is more strongly correlated with temperature, and
      the direction of the correlation indicates that groups living in colder areas
      have relatively shorter legs. The interpretation of the correlations for sitting
      height and relative sitting height is complicated by the fact that the
      correlations of these measurements change when only the low-altitude groups in
      the data set are considered. There are no significant differences in male height
      between linguistic stocks when the analysis is limited to those stocks
      represented by at least five groups. In general, there appears to be more
      patterning in body size and shape variation in South America than there is in
      terms of genetic variation. The correlations between anthropometric measurements
      and climate in South America differ in some ways from those observed for other
      areas of the world.

PMID- 28520263
TI  - Reduction in birth weight associated with smoking among young and older-age
      women.
AB  - This study examined the combined effects of maternal smoking and maternal age on
      birth weight. A sample of 1,851 white, full-term infants (37 to 42 weeks) born to
      primiparous mothers ranging in age from 18 to 41 years was derived from the
      database of the Child Health and Development Studies (CHDS), available through
      the National Technical Information Service (NTIS) of the U.S. Department of
      Commerce. The mothers were classified into three age groups-young, middle-aged,
      and older-aged-corresponding respectively to values below the 15th, between the
      15th and 85th, and at or above the 85th percentile of age. Analyses of the data
      show that the reduction in birth weight associated with maternal smoking when
      compared with nonsmoking averaged 181 gm for the young group (18 to 20 years),
      162 gm for the middle-aged group (21 to 29 years), and 154 gm for the older-aged
      group (30 to 41 years). These differences are independent of total income. Hence
      it appears that the birth weight-reducing effect of smoking is not enhanced among
      women of older reproductive ages (30 to 41 years). Furthermore, the reduction in
      birth weight is dose responsive. That is, the greater the number of cigarettes
      smoked per day, the lower is the resulting mean birth weight and the higher is
      the proportion of low-birth-weight infants.

PMID- 28520264
TI  - War trauma lingers on: Associations between maternal posttraumatic stress
      disorder, parent-child interaction, and child development.
AB  - Maternal traumatization has been proposed as a risk factor for child development,
      but the mechanisms involved are poorly understood. This study analyzed the
      interrelations among maternal posttraumatic stress symptoms, parent-child
      interaction (emotional availability), and infants' psychosocial functioning and
      development among 49 asylum-seeker and refugee mothers and their children (18-42
      months). Measures included assessment of mothers' trauma and comorbid symptoms
      (Harvard Trauma Questionnaire: R.F. Mollica et al., 1992; Hopkins Symptom
      Checklist: L. Derogatis, R. Lipman, K. Rickels, E. Uhlenhuth, & L. Covi, 1974),
      emotional availability within parent-child interaction (Emotional Availability
      Scales: Z. Biringen, 2008), and infants' psychosocial functioning (Child Behavior
      Checklist: T.M. Achenbach & L.A. Rescorla, 2000) and development (Bayley Scales
      of Infant Development: B.F. van der Meulen, S.A.J. Ruiter, H.C. Spelberg, & M.
      Smrkovsky, 2000). The results show that higher levels of maternal posttraumatic
      stress symptoms are associated with a higher level of psychosocial problems of
      infants, but not with delays in their mental or psychomotor development. The
      results also show that higher levels of maternal posttraumatic stress symptoms
      are associated with higher levels of insensitive, unstructuring, or hostile, but
      not intrusive, parent-child interactions. Infants show lower levels of
      responsiveness and involvement to their traumatized mothers. Parent-child
      interaction did not function as a mediator between maternal trauma symptoms and
      infants' psychosocial functioning. Results are discussed in relation to the
      dyad's regulation of emotions. Results implicate a need to reestablish attunement
      between traumatized mothers and their nontraumatized children.

PMID- 28520265
TI  - Biological and physiological markers of tactile sensorial processing in healthy
      newborns.
AB  - The main objective of this review is to provide a descriptive analysis of the
      biological and physiological markers of tactile sensorial processing in healthy,
      full-term newborns. Research articles were selected according to the following
      study design criteria: (a) tactile stimulation for touch sense as an independent
      variable; (b) having at least one biological or physiological variable as a
      dependent variable; and (c) the group of participants were characterized as full
      term and healthy newborns; a mixed group of full-term newborns and preterm
      newborns; or premature newborns with appropriate-weight-for-gestational age and
      without clinical differences or considered to have a normal, healthy
      somatosensory system. Studies were then grouped according to the dependent
      variable type, and only those that met the aforementioned three major criteria
      were described. Cortisol level, growth measures, and urinary catecholamine,
      serotonin, and melatonin levels were reported as biological-marker candidates for
      tactile sensorial processing. Heart rate, body temperature, skin-conductance
      activity, and vagal reactivity were described as neurovegetative-marker
      candidates. Somatosensory evoked potentials, somatosensory evoked magnetic
      fields, and functional neuroimaging data also were included.

PMID- 28520266
TI  - Maternal attachment representations and the development of very low birth weight
      premature infants at two years of age.
AB  - There is a consensus that prematurity could increase the risk of attachment
      impairment. We studied 90 premature children with very low birth weights (<1,500
      g) and 96 healthy children born at term with similar age and sociodemographic
      characteristics. Our objective was to assess maternal stress and attachment
      representations, and compare development indices on both groups at 2 years of
      age. Premature infants had a medium-to-severe degree of immaturity and biological
      risk (M gestational age = 29.98 weeks; birth weight = 1,159.76 g), with 57%
      staying in the ICU >=1 week. These children born prematurely had lower scores on
      the development indices within the normal range. Mothers of premature infants (n
      = 74) reported higher levels of stress during their first year of life (59%) than
      did controls (41%), but no significant differences were detected in maternal
      attachment discourse between the two groups. The findings confirm that premature
      birth has a great influence on maternal emotional responses and the health and
      development of children in the first years of life, and indicate that stress
      responses in parents and warning signs for attachment problems should be assessed
      as early as possible.

PMID- 28520267
TI  - Parental involvement in home visiting: Interpersonal predictors and correlates.
AB  - Parents' commitment to and usage of early intervention are key variables in
      understanding discrepancies in families' susceptibility to these services.
      Although the important role of fathers in infant development is widely
      recognized, early interpersonal predictors of paternal involvement in home
      visiting programs have been understudied. This article aims to fill this gap by
      regressing parents' postnatal involvement on prenatal partnership satisfaction
      and quality of the helping relationship in a sample of 124 socially and
      financially disadvantaged families. Paternal program engagement was predicted by
      partnership satisfaction whereas the perceived quality of the helping
      relationship best predicted maternal program engagement, with demographical
      characteristics controlled. Maternal program engagement also mediated the
      relationship between partnership satisfaction and paternal program engagement.
      The results are discussed against the theoretical background.

PMID- 28520268
TI  - Colic: What's maternal mental health got to do with it?
AB  - Families can benefit when pediatric and mental health professionals have a
      greater appreciation of psychological and relational issues that arise in the
      course of caring for an infant with colic. The Infant Behavior, Cry, and Sleep
      Clinic is a multidisciplinary, clinical intervention for parents who identify
      infant crying as adversely affecting infant, parental, and/or family functioning.
      Pairing pediatric and mental health expertise provides parents with strategies to
      manage infant colic within a context that recognizes parental mental health
      needs. Clinical case material illustrates varying responses and degrees of
      psychological distress in mothers whose infants have colic. Treatment approaches
      to colic that take into account maternal mental health needs may contribute to
      more optimal infant, maternal, and family outcomes.

PMID- 28520269
TI  - Mothers' affect dysregulation, depressive symptoms, and emotional availability
      during mother-infant interaction.
AB  - Maternal affect dysregulation and maternal depressive symptoms were examined as
      predictors of maternal emotional availability (EA) during mother-infant
      interaction in a nonclinical sample. In particular, we investigated if affect
      dysregulation predicts EA and is more important than are depressive symptoms in
      predicting EA. Questionnaire measures and 30 min of free play were obtained from
      46 mothers of 4- to 5-month-old infants. Mothers' self-reported affect
      dysregulation was inversely related to EA, but mothers' depressive symptoms were
      not related to EA. More specifically, mothers' tendency to use unhealthy
      externalizing behaviors to reduce tension and distress predicted less EA. These
      results suggested that even in relatively low-risk samples, mothers' self
      reported affect dysregulation, particularly the tendency to act out
      inappropriately in response to tension and distress, may be a more proximal
      predictor of EA than are depressive symptoms.

PMID- 28520270
TI  - Psychotherapy groups and individual support to enhance mental health and early
      dyadic interaction among drug-abusing mothers.
AB  - The purpose of this controlled study was to examine the outcome of psychodynamic
      mother-infant group psychotherapy (PGT) outpatient intervention for drug-abusing
      perinatal mother-infant dyads. PGT comprised 20 to 24 weekly 3-hr sessions with 3
      to 5 months of follow-up. A comparison intervention group was formed of mothers
      participating in individually tailored psychosocial support (PSS) lasting, on
      average, 12 months and providing mother-infant support and practical counseling.
      We hypothesized that positive changes would occur in maternal drug abuse, mental
      health, and mother-infant interaction, especially in the PGT group due to its
      more intensive therapeutic focus. Participants were 26 drug-abusing dyads in PGT,
      25 in PSS, and 50 dyads in a non-drug-abusing comparison group. Assessments were
      pre-intervention and at 4 and 12 months' follow-up, including maternal depressive
      symptoms and mother-child interaction assessed by the Emotional Availability
      Scales (EA). As hypothesized, in dyadic interaction maternal hostility decreased
      significantly in the PGT group, and intrusiveness decreased in both intervention
      groups, but especially in the PTG group. However, both interventions showed a
      general improvement in the quality of mother-infant interaction. They also
      succeeded in sustaining high maternal abstinence, treatment retention, and
      alleviating depressive symptoms. The findings are discussed in relation to
      preventing negative transgenerational interaction patterns in the high-risk
      dyads.

PMID- 28520271
TI  - Development and initial validation of an outcome measure for home visitation: The
      healthy families parenting inventory.
AB  - The Healthy Families Parenting Inventory (HFPI) is a 63-item outcome measure that
      was designed to examine change in nine parenting-related domains. The HFPI was
      developed to respond to the need for an outcome measure for home visitation
      programs that is relevant to the intervention, sensitive to change, and
      appropriate with a diverse participant base, and would produce data that are
      immediately useful in practice. The authors detail the steps in the development
      and initial validation of the HFPI. The pattern of inter-item and item-to
      subscale correlations as well as an exploratory factor analysis and sensitivity
      to change analysis support the nine-factor model of the HFPI.

PMID- 28520272
TI  - A focus on polarity: Investigating the role of orientation cues in mediating
      student performance on mRNA synthesis tasks in an introductory cell and molecular
      biology course.
AB  - The central dogma has served as a foundational model for information flow,
      exchange, and storage in the biological sciences for several decades. Despite its
      continued importance, however, recent research suggests that novices in the
      domain possess several misconceptions regarding the aforementioned processes,
      including those pertaining specifically to the formation of messenger ribonucleic
      acid (mRNA) transcripts. In the present study, we sought to expand upon these
      observations through exploration of the influence of orientation cues on
      students' aptitude at synthesizing mRNAs from provided deoxyribonucleic acid
      (DNA) template strands. Data indicated that participants (n = 45) were proficient
      at solving tasks of this nature when the DNA template strand and the mRNA
      molecule were represented in an antiparallel orientation. In contrast,
      participants' performance decreased significantly on items in which the mRNA was
      depicted in a parallel orientation relative to the DNA template strand.
      Furthermore, participants' Grade Point Average, self-reported confidence in
      understanding the transcriptional process, and spatial ability were found to
      mediate their performance on the mRNA synthesis tasks. Collectively, these data
      reaffirm the need for future research and pedagogical interventions designed to
      enhance students' comprehension of the central dogma in a manner that makes
      transparent its relevance to real-world scientific phenomena. (c) 2017 by The
      International Union of Biochemistry and Molecular Biology, 45(6):501-508, 2017.

PMID- 28520273
TI  - Efficacy of a Targeted Drug Delivery on-Demand Bolus Option for Chronic Pain.
AB  - BACKGROUND AND OBJECTIVES: Intrathecal targeted drug delivery systems
      historically required physician office visits for dose adjustment to manage
      fluctuating pain. A wireless device now enables patients to supplement their
      basal intrathecal infusion with a programmed on-demand bolus dose. We sought to
      quantify the change in oral breakthrough opioid need associated with the use of
      an intrathecal bolus in comparison to those treated with the basal infusion
      alone. METHODS: Demographic, dosage, bolus usage and longevity data were
      extracted from the historical medical record of 69 patients (18/51
      bolus/nonbolus) followed continuously at our center. Medication consumption and
      Pain Disability Index measures were obtained at baseline and most recent follow
      up. RESULTS: Among patients with the bolus option, only 2 (11%; confidence
      interval [CI] 0% to 26%) continued to require oral opiates to manage breakthrough
      pain compared to 29 (57%; CI 43% to 71%) without the bolus option. The Pain
      Disability Index score decreased by 19% in patients with the bolus option and by
      25% in those with the basal infusion. Total daily intrathecal opioid intake was
      34% lower in the group with the bolus device. CONCLUSIONS: Utilizing an
      intrathecal bolus to treat incident pain was a safe way to manage unpredictable
      breakthrough pain and may represent a cost-saving opportunity by eliminating the
      need for oral analgesic medications.

PMID- 28520274
TI  - Influence of behavioral concerns and early childhood expulsions on the
      development of early childhood mental health consultation in Colorado.
AB  - This article examines how the Colorado study Children With Social, Emotional and
      Behavioral Concerns and the Providers Who Support Them (S.D. Hoover, 2006) was
      used to advance a statewide agenda for early childhood mental health consultation
      in Colorado. The study involved a survey of licensed childcare providers
      throughout the state asking about the behavior of children in their care and
      their responses to that behavior. Exclusion of children from early care and
      education settings due to challenging behavior was found to be a significant
      problem taking a toll on families, children, and early care and education
      providers. Importantly, results from the survey indicated that the rate of
      exclusion of children from care due to challenging behavior was lower for family
      childcare providers who had access to mental health consultation. Recommendations
      are offered regarding the infrastructure needed to sustain mental health
      consultation capacity in early care and education settings, and related policies
      and practices.

PMID- 28520275
TI  - Forgotten survivors of intimate-partner violence: The role of gender and
      mothering in infant development.
AB  - Although gender and mothering are critical factors in the development of infants
      exposed to intimate-partner violence (IPV), the majority of research has focused
      on school-age and adolescent populations. The aim of this study was to
      investigate the moderating effect of gender in the relationship between mother
      infant interaction and infant development in families of IPV. Maternal report was
      used to measure infants' cognitive and social functioning while mother-infant
      interaction quality was assessed through an observational measure. Participants
      consisted of 44 mothers and their infants (4-43 months of age). While male
      infants showed poorer fine motor, problem-solving, and personal-social skills
      than did their female counterparts, comparable gross motor and communication
      skills were demonstrated. Moderator analysis for gender indicated that the
      association among maternal cognitive growth fostering and gross motor skills was
      significantly stronger for boys than it was for girls. No other moderator effects
      were detected. Analysis examining age, gender by age, and infant competencies did
      not reveal significant effects. Implications for clinical practice are
      considered, with special attention paid to women as mothers.

PMID- 28520276
TI  - Expanding early childhood mental health consultation to new venues: Serving
      infants and young children in domestic violence and homeless shelters.
AB  - The number of infants and young children affected by homelessness and domestic
      violence is growing, and the effect of these experiences on children is wide
      ranging. Early childhood mental health consultation (ECMHC) has expanded to these
      settings to help the adults attend to very young children whose needs are often
      obscured by families' crises. Recent research in ECMHC to childcare has cited the
      salience of the consultant-consultee relationship as the central contributor to
      positive change in caregiver's behavior and children's experience. This article
      explores the similarities and variations in the consultant's way of being that
      are necessary to expand this relationship-based ECMHC model to adult-focused
      settings. This has incorporated a combination of consultative shifts: expanded
      training, appreciation for families' survival priorities, attention to the
      effects of unavoidable adult decisions on children, increased tolerance for the
      affect this raises in parents and caseworkers, and greater efforts to create
      space for reflection and thinking. Caseworkers' attenuated contact with and
      limited prior knowledge about young children creates challenges in identifying
      and responding to concerns about children. The particular systemic and relational
      difficulties that emerge in shelters and that influence caseworkers'
      responsiveness to clients are explored.

PMID- 28520277
TI  - A multilevel analysis of consultant attributes that contribute to effective
      mental health consultation services.
AB  - A positive relationship between the mental health consultant (MHC) and early care
      and education staff is considered important for achieving positive early
      childhood mental health consultation outcomes, but little is known about the
      attributes of MHCs that contribute to relationships with staff and to staff
      reported child outcomes. This study was a secondary analysis of 57 MHCs and 407
      Head Start staff who responded to the Head Start Mental Health Services Survey.
      Hierarchical linear models examined the relationship between five attributes of
      MHCs and staff reports of improved child outcomes and a positive relationship
      with the MHC. The results suggest that MHC reports of positive relationships with
      staff, positive relationships with families, and high levels of supervision and
      support are positively associated with staff reports of positive relationships
      with the MHC (p < .05). None of the MHC-reported attributes were associated with
      staff-reported child outcomes.

PMID- 28520278
TI  - Assessing fidelity for early childhood mental health consultation: Lessons from
      the field and next steps.
AB  - Early childhood mental health consultation (ECMHC) has become a common approach
      to delivering mental health services and supports for young children, their
      families, and the early care and education community. While many states and
      communities are implementing some form of ECMHC, the evidence base is still
      developing. One obstacle to building a rigorous evidence base has been a lack of
      focus on fidelity measurement, and one barrier to fidelity assessment has been a
      lack of a common framework for the essential components of effective ECMHC. This
      article briefly summarizes the development of a conceptual model for effective
      ECMHC based on a qualitative study of six ECMHC programs with positive outcomes
      (F. Duran et al., 2009). The common components and processes derived from those
      six programs are then used to articulate an approach for operationalizing
      fidelity. Specific examples of strategies used to support fidelity by three of
      the six programs are highlighted. We close with a discussion of the implications
      of these approaches and suggestions for next steps in defining a consensus-based
      model for measuring fidelity to ECMHC services. Abstracts translated in Spanish,
      French, German, and Japanese can be found on the abstract page of each article on
      Wiley Online Library at http://wileyonlinelibrary.com/journal/imhj.

PMID- 28520279
TI  - Therapeutic play within infant-parent psychotherapy and the treatment of infant
      feeding disorders.
AB  - This clinical article presents an infant mental health approach to the treatment
      of feeding disorders in infants and toddlers that involves the infant-parent
      psychotherapist directly working with the infant's representations within infant
      parent psychotherapy sessions. The treatment is informed by an assessment of the
      infant's emotional development, subjective experience, and the dynamics of the
      infant-parent relationship. This model involves therapeutically using play and
      words with infants and draws upon concepts from D.W. Winnicott and attachment
      theory as well as principles from the psychodynamic treatment of posttraumatic
      stress disorder in infants. The model was developed from clinical work over 2
      decades in a tertiary pediatric hospital with infants who presented with feeding
      disorders ranging from breast or bottle refusal, refusal to wean onto solids,
      feeding aversion, tube dependency, and failure to thrive.

PMID- 28520280
TI  - The consultation relationship-From transactional to transformative: Hypothesizing
      about the nature of change.
AB  - Increasing numbers of young children with significant social and emotional
      difficulties are being identified in childcare settings. Early Childhood Mental
      Health (ECMH) Consultation has been identified as a promising practice in
      stemming the tide of this troublesome trajectory. While ECMH Consultation is
      credited with promoting children's positive development, diminishing difficult
      behaviors, and reducing expulsion rates, the mechanisms of this transformative
      process are only beginning to be investigated. Recent research cites the salience
      of the relationship between a consultant and consultee as the central contributor
      to positive change in childcare-center climate and child outcomes. This article
      delineates characteristics of a beneficial consultative relationship and
      postulates the clinical process by which change in childcare providers' behavior
      occurs as a result of having experienced such a relationship. Paralleling the
      traits of contingent caregiving, the consultative stance, a posture of mutuality,
      reciprocity, and positive regard creates an intersubjective space for reflection,
      repair, and, when necessary, adaptation. Based on perceptual shifts or
      expansions, the providers' attitude and approach toward children in their care is
      amended, in turn promoting positive change in the child and classroom atmosphere.

PMID- 28520281
TI  - Parental representations: A systematic review of the working model of the child
      interview.
AB  - This review provides an overview of results that have been obtained in studies
      using the Working Model of the Child Interview (WMCI). The WMCI is a structured
      interview that assesses parents' internal working models of the relationship with
      their young children. From the current infant mental health perspective,
      evaluating the quality of parents' representations about the infant-parent
      relationship is the main focus in the assessment and treatment of infants and
      their parents. Empirical quantitative studies (N = 24 articles) in which the WMCI
      was used for data collection were used for analysis. The distribution of
      balanced, disengaged, and distorted representations differed among various study
      populations. Parents' internal representations as reflected in their narratives
      about their child are affected by various factors such as maternal, child, and
      demographic characteristics. The WMCI is a valid and useful clinical and research
      tool that can be used in future studies examining the role of parental
      representations in infant development.

PMID- 28520282
TI  - Implementing a statewide early childhood mental health consultation approach to
      preventing childcare expulsion.
AB  - State- and local-level mental health administrators and practitioners can work
      collaboratively to provide effective early childhood mental health consultation
      (ECMHC) services that address the growing need in communities to promote healthy
      socioemotional functioning in infants and young children and prevent longer term
      mental health challenges. This article describes one state's model of ECMHC, the
      Child Care Expulsion Prevention Program (CCEP), as well as preliminary evaluation
      findings on consultants' fidelity to the developed approach to service within 31
      counties in Michigan. The CCEP approach is flexible, yet adheres to six
      cornerstones which are essential to effectively and consistently carrying out
      services across local projects, including the provision of relationship-based
      programmatic and child/family-centered consultation, hiring and supporting high
      quality consultants through professional development and reflective supervision,
      ongoing provision of state-level technical assistance, use of evidence-based
      practices, and collaboration with other early childhood service providers. In
      addition to the overview of CCEP's approach and effectiveness, lessons learned
      are provided to guide those engaged in policy development, practice, and applied
      research pertaining to ECMHC. Abstracts translated in Spanish, French, German,
      and Japanese can be found on the abstract page of each article on Wiley Online
      Library at http://wileyonlinelibrary.com/journal/imhj.

PMID- 28520283
TI  - Building the evidence base for early childhood mental health consultation: Where
      we've been, where we are, and where we are going.

PMID- 28520284
TI  - Improved classroom quality and child behavior in an Arkansas early childhood
      mental health consultation pilot project.
AB  - The aim of the current study was to examine the effects of early childhood mental
      health consultation (ECMHC) on teacher-level and child-level outcomes in the
      context of a partnership between community mental health centers in three regions
      of Arkansas and publically funded early education programs (14 intervention sites
      and 4 comparison sites). From 2005 to 2008, 193 teachers participated in the
      study, along with 1,448 children. Data-collection activities included structured
      classroom observations, teacher ratings of children's strengths and behavior, and
      teacher surveys to assess satisfaction with ECMHC services. Results suggest that
      teachers were highly satisfied with the consultation services and that teachers
      receiving the intervention had lower levels of permissiveness and detachment,
      with a trend toward higher levels of sensitivity in interactions with children in
      their classroom. In terms of child outcomes, we found that by the third year of
      the project, children at intervention sites were rated by their teachers as
      having fewer behavior problems and more protective factors.

PMID- 28520285
TI  - Effect of moderate weight loss on ovarian function assessed by salivary
      progesterone measurements.
AB  - The effects of moderate, voluntary weight loss on ovarian function are studied by
      monitoring the daily levels of salivary progesterone in 8 dieting women (18
      cycles) and 9 age-matched controls (19 cycles). Both groups of women were within
      normal standards of weight for height, though the dieters were significantly
      heavier than the controls. Dieters lost weight at an average rate of 1.9 +/- 0.3
      kg/mo during the study. Dieters' cycles during periods of weight loss (weight
      loss cycles) have significantly lower peak levels of luteal progesterone
      (controls 655 +/- 46 pmol/L, weight loss 461 +/- 67 pmol/L; P < 0.005) and lower
      average levels of luteal progesterone (controls 287 +/- 30 pmol/L, weight loss
      214 +/- 23 pmol/L; P < 0.005) than do controls. All control cycles were
      classified as ovulatory by virtue of at least one salivary progesterone reading
      >= 300 pmol/L. Only 62% of the weight loss cycles were classified as ovulatory by
      this criterion. Where longitudinal weight data are available both the magnitude
      and duration of progesterone elevation correlates significantly with net weight
      change during the preceding cycle and show no significant correlation with net
      weight change during the current cycle. Examination of individual profiles
      confirms that the most profound suppression of luteal activity usually occurs
      during post-loss rather than weight loss cycles, even if weight is stable or
      increasing during the post-loss cycle itself. These results, together with field
      studies of African horticultural populations, suggest that human ovarian function
      may be adapted to modulate waiting time to conception in response to trends in
      energetic balance.

PMID- 28520286
TI  - Reciprocal causal influences among malnutrition, growth retardation, and diarrhea
      in preschool children.
AB  - Structural regression models are applied to longitudinal data to study reciprocal
      causal influences between malnutrition and infection in preschool children. Two
      models of three waves (time periods) are applied: a two-variable model, the
      variables being acute malnutrition and diarrhea; and a three-variable model,
      which includes chronic malnutrition as a third variable. Malnutrition is measured
      by standardized weight for age and standardized height for age, and enteric
      infection is measured by diarrhea. The latter is expressed as the number of days
      with diarrhea or fever divided by the number of days at risk in the trimester
      preceding anthropometric assessment. The data used in the analysis were gathered
      as part of a longitudinal study to estimate the effects of nutrition on mental
      and physical growth, conducted by the Institute of Nutrition of Central America
      and Panama (INCAP) in rural Guatemala. The sample comprises 508 children with
      complete data from families residing in four rural villages. Results provide
      evidence of significant causal influence of both diarrhea on acute malnutrition
      and of acute malnutrition on diarrhea. A cumulative effect of acute malnutrition
      on chronic malnutrition that leads to growth retardation is identified.
      Accordingly, interventions aimed at decreasing the causal effect of infection on
      malnutrition, as well as interventions aimed at improving the nutritional
      condition of children, are required.

PMID- 28520287
TI  - Longitudinal growth of high socioeconomic status Guatemalan children analyzed by
      the Preece-Baines function: An international comparison.
AB  - The Preece-Baines model I function, adapted for use with a personal computer, is
      applied to the longitudinal growth records of Guatemalan children and adolescents
      of high socioeconomic status. The fit of the Preece-Baines function to the
      Guatemalan data is compared with those of published analyses of the function
      fitted to the growth of British, Belgian, urban and rural Indian, Australian
      Aborigine, and African children. Guatemalan, British, and Belgian samples share
      generally favorable environments for human development and show few differences
      in the amount and velocity of growth, or in the timing of growth events. Urban
      Indians live under relatively good environmental conditions and are similar to
      Guatemalans in the timing of growth events, but grow more slowly and grow less
      than the Guatemalans, British, or Belgians. Rural Indian, Australian, and African
      samples live in environments that delay or retard growth, and these last-named
      three samples grow more slowly, delay the onset of the adolescent growth spurt,
      and achieve smaller adult height than the Guatemalans. Parameters of the Preece
      Baines model are compared between all samples and show that there are several
      alternate paths in the rate of growth and the timing of adolescent growth events
      that may be taken from childhood to adulthood.

PMID- 28520288
TI  - Inference of a gene and its paths of descent: The Newfoundland example.
AB  - This paper presents various aspects of Pedigree Analysis through a review of a
      study of a Newfoundland genetic isolate. This study has evolved over a number of
      years and involved many researchers. The population came to attention due to a
      greatly enhanced incidence of a variety of lymphoreticular malignancies. Genetic
      analysis shows clearly that there are (at least) two groups of traits. Whereas
      the distribution of the leukaemia and lymphosarcoma cases show no clear
      genealogical pattern, the existence of a single recessive allele causing
      susceptibility to Hodgkin's disease and immunodeficiency in an isolated New
      foundland population can be inferred. There appears to be no heterozygote
      penetrance, but in the period up to 1974 homozygote penetrance was high and
      perhaps complete. More important, the ancestral paths of the allele can be
      inferred. Many ancestral individuals are obligatory carriers, and most others
      have either probability >95% or <5% of having carried the allele. More recently,
      methods were developed and applied in order to investigate linkage of this locus
      to conventional blood group and serum protein marker loci. Although no linkages
      were found, some observed associations were clarified, and some definite non
      linkages established.

PMID- 28520289
TI  - Height and weight differences among South African Urban schoolchildren born in
      various months of the year.
AB  - Among 1,165 subjects aged 6-18 years who were examined once cross-sectionally, a
      significant variation in body height and weight according to the month of birth
      of the subjects was found. All subjects belonged to the so-called Cape Coloured
      community, were born locally, and their parents belonged to the most affluent
      sector of the community. Individuals born in February to July were shorter and
      weighed less (by 13 to 17% of the standard deviation) than those born in August
      to January. These results are similar to those obtained for Canadian children,
      who were measured on their birthdays. Since our individuals were measured only
      once, at the same time of the year, observed differences cannot be ascribed to
      seasonal fluctuations of growth rates prior to measurement but must constitute a
      persistent effect of seasonal fluctuation in earlier growth. Immediate
      environmental conditions (food, temperature, rainfall, and insolation) in the
      Southern Hemisphere fluctuate seasonally 6 months out of phase from those in the
      Northern Hemisphere. Thus the similarity of our findings to those from the
      Northern Hemisphere suggests a factor common for the entire earth, possibly
      related to the ellipsoid shape of the orbit of the planet.

PMID- 28520290
TI  - Blood lead levels and growth status of children.
AB  - Several studies have shown that elevated blood lead (Pb) levels in children are
      associated with decreased growth. Among 139 children aged 1 to 10 years (66 male,
      73 female) who attended a Pb clinic in Dallas, Texas, growth was decreased by 1.6
      cm in height, 1.4 kg in weight, and 0.6 cm in head circumference for each 10
      MUg/dl increase in blood Pb. Consistent with previously reported effects of Pb,
      several clinical symptoms (hearing deficit, dental problems, hyperactivity) were
      increased in frequency among children with high blood Pb levels (XPb = 34.6
      MUg/dl +/- 5.6) compared to the children in the low Pb level group (XPb = 11.9
      MUg/dl +/- 3.3). Interestingly, pica was significantly increased in frequency
      among children in the high Pb group, indicating oral consumption of non-food
      matter was a major source of Pb intoxication. These results suggest that
      increased Pb level is an important risk factor for growth deficits in children.

PMID- 28520291
TI  - Infant-feeding practices and childhood stature in three ethnic groups.
AB  - Inconsistencies in the literature on the relationship of infant feeding practices
      to stature were explored in a tri-ethnic sample of 3- or 4-year-old children.
      Measures of child stature, maternal stature, child age, type of infant milk
      feeding, time of introduction of high fat and high carbohydrate foods, and social
      characteristics were analyzed with multivariate statistical techniques. No
      statistically significant bivariate or more complex relationships were detected
      between the modes of infant-feeding and child stature. The best-fitting
      regression equation accounted for 61% of the variance, revealing strong
      relationships with child age and maternal height, and weak relationships with
      child adiposity, gender, and ethnicity. The present results indicate that there
      is little likelihood that metabolic effects induced by methods of infant-feeding
      affect stature, at least among 3- or 4-year-old children.

PMID- 28520292
TI  - Association of bioelectrical resistance with estimates of fat-free mass
      determined by densitometry and hydrometry.
AB  - The relationship of whole-body electrical resistance (WBR) to fat-free mass,
      derived from densitometry (FFMDb ), hydrometry (FFMTBW ), and densitometric fat
      free mass corrected for hydration (FFMD+W ) was investigated in three independent
      samples (AZ, IL, CA). Subjects included 75 males and 75 females ranging in age
      from 18 to 32 years. Whole-body resistive index (WBRI) computed as height2
      /resistance was highly correlated to FFMDb , FFMTBW , and FFMD+W (r = 0.97, 0.95,
      and 0.97, respectively). Multiple regression analysis was employed to develop
      prediction equations for FFMDb , FFMTBW , and FFMD+W . In each prediction
      equation, WBRI was the single best predictor. Accounting for sex and variation in
      body weight significantly improved the prediction equations, by increasing the R2
      s to 0.95, 0.94, and 0.96 and decreasing the SEEs to 2.6, 3.2, and 2.5 kg, for
      FFMDb , FFMTBW , and FFMD+W , respectively. Similarity of the SEEs between
      methods (less than 1.0 kg difference) suggests consistency in the precision of
      WBRI estimates for body composition.

PMID- 28520293
TI  - Dynamic and static measures of growth among pre- and postmenarcheal females in
      rural Bangladesh.
AB  - Height and weight for age and height and weight velocity are examined in a sample
      of Bangladeshi adolescents aged 10-20 years with an average age at menarche of
      15.8 years. Interpopulation differences between pre- and postmenarcheal girls are
      assessed and age patterns are compared to standards of U.S. and British
      adolescents. Bangladeshi adolescents are shorter and lighter for their age and
      lighter for their height than are U.S. adolescents. The growth spurt in height
      and weight is delayed and spread out over time, and growth rates are lower
      throughout the spurt when compared to British and U.S. girls. As in developed
      countries, most girls attain menarche after peak height velocity, while weight
      gain per year is highest around the time of menarche. There is no significant
      relationship between age at menarche and height or weight at menarche.

PMID- 28520294
TI  - Differences in the subcomponents of fat-free body in relation to height between
      black and white children.
AB  - The individual subcomponents of fat-free body (FFB) in relation to height were
      investigated in 131 white (N = 85) and black (N = 46) males (MW, MB) and 108
      white (N = 63) and black (N = 45) females (FW, FB), aged 8 to 18 years. Bone
      mineral content (BM), bone width (BW), and bone mineral index (BMI) were measured
      using photon absorptiometry; total body water (TBW) was measured by deuterium
      dilution; body density was measured by hydrostatic weighing, correcting for
      residual lung volume; and estimates of lean body mass (LBM) were made from total
      body potassium (40 K spectroscopy). The subcomponents of the FFB-BM, BW, BMI,
      TBW, and K-were regressed on the log of height to determine the exponent of the
      independent variable (Ht) that would most accurately predict the dependent
      variables (BM, BW, BMI, TBW, K) within gender and race. Regression equations were
      derived for each of the variables used to represent a subcomponent of the FFB on
      Ht. Significant (P < .05) racial differences were found in BW, with the MB having
      wider bones than the MW. Significant racial differences were observed in BMI with
      FB demonstrating a greater difference across height than FW. Racial differences
      in BM and TBW approached significance within the female sample. At heights
      greater than the mean of a typical pubescent child, the males had higher values
      for each of the variables, except for BMI, than did the females. The lower BMI
      values observed in males indicated that the rate at which male bones grow in
      width was greater than their rate of mineralization. Within the male sample,
      blacks had higher bone mineral than whites with the magnitude of these
      differences dependent on the variable under consideration. Within the female
      sample the blacks had greater amounts of BM and BMI in relation to height, while
      the whites had a greater amount of K. Therefore, the magnitude of the differences
      between blacks and whites in the subcomponents of the FFB are dependent on
      gender, stature, and the particular subcomponent of the FFB under consideration.

PMID- 28520295
TI  - Estimation of energy expenditure in Western Samoa, American Samoa, and Honolulu
      by recall interviews and direct observation.
AB  - Reliable and accurate estimates of energy expenditure are a fundamental
      requirement for research on energy balance, energy flow, and other biocultural
      phenomena. Cross-validation of estimates derived from more than one time
      allocation method can detect sources of bias and may lead to estimates which are
      more credible than those from activity recalls used alone. This paper compares 24
      hour activity recalls and direct observations as methods of estimating the energy
      expenditure of 145 18-37-year-old Samoans residing in rural Western Samoa,
      American Samoa, and Honolulu. Daily energy expenditure was estimated on 2
      workdays by activity recalls (n = 214) or by focal-individual observations (n =
      91). Samoan men expend 2,900-3,400 kcal/day and women expend 2,250-2,650
      kcal/day. Estimates of energy expenditure in the Western Samoa sample are
      comparable to other subsistence horticultural societies, while the American
      Samoan and Honolulu samples are comparable to other sedentary working
      populations. Group estimates from recall interviews are 100-400 kcal/day higher
      than from observations, although this is only a difference of 5-10%.
      Overestimation of energy expenditure is more evident at higher work intensities
      than for sedentary activities. The apparent exaggeration of strenuous activity in
      this, and other, studies indicates that without cross-validation, self-reported
      activity data may often be confounded by an unknown amount of subjective bias.

PMID- 28520296
TI  - Isonymic analysis of post-famine relationships in the Ards Peninsula, N.E.
      Ireland: Effects of geographical and politico-religious boundaries.
AB  - During and in the decades after the Irish Famine of 1846 to 1851, the population
      of the Ards Peninsula, Co. Down, both declined in numbers and changed in its
      composition. In 1863 the surnames of all resident householders were collected as
      part of a national valuation. These data have been used to calculate random
      isonymy values between civil parishes and the resultant matrix plotted by
      nonmetric multidimensional scaling. The results revealed both a major
      geographical barrier to gene flow, and politico-religious boundaries in existence
      since the early 17th century. The inter-relationships between random isonymy,
      geographical distance, and religious denominational frequencies within the
      peninsula were investigated by multiple regression analysis. While geographical
      influences predominated over short and long distances, in the intermediate
      distance range religion played the dominant role. The net effect of these
      subdivisions, in combination with famine-associated population losses, would have
      been to reduce local effective population sizes significantly, thus enhancing the
      potential for genetic drift and random inbreeding.

PMID- 28520297
TI  - The Optimal Approach for a Superior Hypogastric Plexus Block.
AB  - INTRODUCTION: Superior hypogastric plexus block (SHGPB) is technically difficult,
      and an accurate procedure is required to avoid potential complications. We
      attempted to determine the reference angles for fluoroscopy-assisted SHGPB and to
      establish a predictor as a guide to select the optimal approach between the
      classic posterior approach and transdiscal approach. METHODS: Abdominopelvic
      computed tomography (CT) scans from 268 patients diagnosed with pelvic
      malignancies were examined. The oblique and axial angles needed for the
      fluoroscope were measured both for posterior and transdiscal approaches by
      simulating the needle trajectory on CT imaging. We developed an SHGPB index
      defined by the ratio (%) of the interposterior iliac border distance to the L5
      body transverse diameter, which represents the relative transverse diameter of
      the bony pelvis. We evaluated whether it can help select the optimal approach for
      the SHGPB between the posterior and transdiscal approaches. RESULTS: Males had a
      significantly smaller angle than females (right oblique angle for posterior
      approach, males 14 [range 12 to 17] degrees vs. females 19 [range 16 to 23]
      degrees; P < 0.001). An SHGPB index of < 150 was an independent predictor for
      failure of the classic posterior approach (odds ratio 31.3, 95% confidence
      interval 5.1 to 104.7). CONCLUSIONS: The optimal right oblique angle of
      fluoroscopy for the posterior approach is 13 degrees  to 15 degrees  in males and
      19 degrees  to 20 degrees  in females. The transdiscal approach may be favored
      over the posterior approach when the bony pelvis is narrow relative to the target
      vertebral body, which can be measured by the SHGPB index being < 150.

PMID- 28520298
TI  - Longitudinal analysis of deciduous tooth emergence in Indonesian children. I.
      Life table methodology.
AB  - Deciduous tooth emergence was investigated in a sample of 468 children from
      central Java. The subjects were examined every 35 days for up to 2 years.
      Statistics on the timing of emergence for each tooth were derived from actuarial
      life table estimates, and male and female survivorship curves of tooth emergence
      were compared for statistical sex differences. Javanese children exhibited
      delayed emergence compared to other populations. No overall pattern of sexual
      dimorphism was detected, although upper first molars emerged significantly
      earlier in females. A comparison of emergence sequence polymorphisms between
      Javanese, Finnish, and Japanese children revealed that the i1-i2-m1-c-m2 sequence
      is most common in all three populations, but each shows a uniquely higher
      proportion of one or more less common polymorphisms.

PMID- 28520300
TI  - Is there a selective rural-urban migration in respect to height and weight?
AB  - Height and weight were examined in rural-urban premigrants from heavily
      depopulating regions in the countryside. The analysis involved children, 5.75
      8.74 years, from rural schools in two rural districts in Poland, Bystrzyca
      Klodzka and Pinczow, in 1978. Migrants were identified while reexamining the
      children in the same schools 10 years later, i.e., in 1988, and by using
      information from local census registers. The premigrants from the villages of
      Klodzka Pinczow and Pinczow districts do not differ in height and weight when
      compared to the total population of rural children examined in each district. The
      comparison of height and weight in premigrants and nonmigrants in groups
      homogeneous for SES of the children's families indicates that if the SES of rural
      families is very low, individuals smaller in size tend to remain in the rural
      areas. When SES of the rural population improves, migration of the young seems to
      be random in respect to height and weight.

PMID- 28520299
TI  - Measurement errors for a portable device measuring short-term growth.
AB  - A field trial was conducted for a portable Knee Height Measuring Device (KHMD).
      Measurement errors for the machine, within and between observers (intraobserver
      and interobserver) and within subjects (intrasubject), were calculated from
      repeated observations of two anthropometrists on 40 children, 8 and 9 years of
      age. Interobserver technical error (0.452 mm) was larger than that published by
      the KHMD developers, but intraclass reliabilities are still very high (0.9975
      0.9983). Attained size and fatness of subjects were not significantly correlated
      with interobserver measurement errors. Observed errors suggest they are
      sufficient to allow detection of knee height growth over periods of time much
      shorter than could be accomplished using more conventional anthropometry.

PMID- 28520301
TI  - Comparative genetic variance and heritability of head and facial traits in
      northwest Indian and Belgian twins.
AB  - Genetic variance analysis of 13 head and facial traits is considered in samples
      of Northwest, Indian and Belgian twins. Modified t tests, based on the nested
      structure of twin data, indicate differences between monozygotic (MZ) and
      dizygotic (DZ) mean values of bigonial diameter in Indian females and in Belgian
      males, i.e., for only two of 52 instances. Heterogeneity of variance is observed
      in about 30% of the craniofacial traits in both samples, invalidating
      conventional within-pair genetic variance estimates for these traits. Patterns of
      environmental bias on zygosities differ between sexes within the same population
      and also between the two samples. Revised average genetic variance ratios are
      higher in Indian than in Belgian twins. Male twins manifest, on average, higher
      genetic variance ratios than female twins in both the samples. There is stronger
      evidence of enviornmental covariance in MZ than in DZ twins for both Indian and
      Belgian twins. The pattern of intraclass corrlations, based on average values, is
      as follows: ?rMZ > ?rMZ > ?rDZ >= ?rDZ in the Indian twins and ?rMZ > ?rMZ > ?rDZ
      > ?rDZ in the Belgian twins.

PMID- 28520302
TI  - Malawi maternal and child nutrition study: Study design and anthropometric
      characteristics of children and adults.
AB  - The Malawi Maternal and Child Nutrition (MMCN) Study is a three-year longitudinal
      investigation of some of the determinants and consequences of protein-energy
      malnutrition in a rural African population. This paper describes the
      anthropometric characteristics of children and adults based on the baseline
      census conducted in the 89 villages included in the MMCN Study. Mean length-for
      age of Malawian children (birth-60 months) is very low (Z-score = -2.21) and,
      unlike most other populations, continues to decline with advancing age. Weight
      for-length is more nearly normal (mean Z-score = -0.21) but shows the same age
      related decline between birth and 18 months (and subsequent return to normal
      levels) as that seen in many other developing countries. This age pattern is also
      reflected in upper arm anthropometry, notably estimated arm fat area. Length-for
      age and weight-for-age of children is associated with birthweight in the 40% of
      children having health cards, but body composition indicators do not show the
      same consistent association with birthweight at all ages. Adult men and women
      have very low skinfold thicknesses relative to U.S. blacks (50-60% of U.S.
      medians at the triceps and subscapular sites). Estimated upper arm cross
      sectional muscle (plus bone) area for Malawian men averages 74% of U.S. white
      values, while that for women averages 100% of U.S. white values.

PMID- 28520303
TI  - Influence of chronic sublethal cyanide on body weight in neonatal swine:
      Implications for humans consuming cassava (Manihot esculenta).
AB  - The consumption of CN- containing foods (particularly cassava) is pervasive among
      millions of humans throughout the tropics, yet very little is known about the
      long-term implications of this dietary pattern on growth. In this study Liberian
      (West African) levels of dietary cyanide (CN- ) intakes were replicated in
      juvenile swine for 24 weeks to quantify the effects of specified, chronic,
      sublethal doses of this metabolic poison on body weight. Twelve female and male
      littermates were partitioned into a control (O mg CN- ) and 3 treatment groups
      (1.2, 0.7, or 0.4 mg CN- per kg body weight per day). CN- treatments depressed
      absolute weight gain in a dose-dependent manner with significant differences
      apparent as early as week 12. Thyroid hormones T3 and T4 and fasting blood
      glucose values were evaluated at 6-week intervals. T3 levels were ostensibly
      suppressed and blood glucose values elevated with increasing CN- ingestion. Serum
      thiocyanate (SCN- ), the major metabolite of sublethal CN- ingestion, was
      positively correlated with CN- intake loads (r = 0.83, P < 0.01). Hypothesized
      physiological foundations for these observations and theoretical implications for
      human growth are elaborated.

PMID- 28520304
TI  - Hemoglobin concentration and working capacity of nonpregnant rural women of the
      Kathmandu valley of Nepal.
AB  - The relationship between hemoglobin concentration, nutritional status, and
      working capacity of village women in Nepal was investigated. Subjects were 71
      nonpregnant women (ages 18 to 60 yr) living at altitudes ranging from 1,300 to
      1,600 m in a rural area near Kathmandu. Half of the women (51%) performed manual
      wage labor on a daily basis, working as field hands during the agricultural
      season and breaking rocks into gravel during the remainder of the year; the
      remaining 49% worked only in their own fields or in exchange labor groups. Anemia
      was mild but widespread; 62% of the women had hemoglobin concentrations of 12.0
      gm/dl or lower. Mean hemoglobin for the total sample was 11.7 +/- 1.4 gm/dl
      (range 7.2 to 15.6 gm/dl). A step test was used to measure working capacity, and
      expired air samples were analyzed for O2 and CO2 using a Scholander 0.5 ml gas
      analyzer. Caste and ethnic groups differed significantly with respect to
      hemoglobin concentration (P < 0.005) and heart rate response to submaximal
      exercise (P < 0.001), but not in anthropometric measurements. Among those ethnic
      groups accustomed to daily physical labor, i.e., the Newars and Tamangs, lower
      hemoglobin concentration was correlated significantly with higher heart rate,
      higher oxygen uptake, and lower mechanical efficiency during submaximal aerobic
      exercise.

PMID- 28520305
TI  - Family resemblance for patterns of growth in early childhood.
AB  - Parameters of the Jenss curve representing linear and non-linear components of
      growth in early childhood were fitted to longitudinal recumbent length and weight
      measurements from participants in the Fels Longitudinal Growth Study. Nuclear
      family correlations were estimated for each of four Jenss parameters (a linear
      intercept and slope and a non-linear intercept and degree of curve) for length
      and for weight. The TAU path model was fit to the correlations, in order to
      estimate path coefficients representing transmissibility from parent to child (t2
      ) and non-transmissible sibling resemblance (s). Likelihood ratio chi2 tests
      suggest that significant family resemblance exists for each Jenss parameter for
      both variables. Transmissibility is the major component in family resemblance for
      the linear and non-linear intercepts for length, whereas non-transmissible
      sibling environmental effects are dominant for three of the four weight
      parameters. The source of the family resemblance for the remaining parameters
      could not be pinpointed. The linear slope and degree of curve for weight are more
      similar for same sex siblings than for opposite sex pairs, suggesting that the
      degree of shared sibling environment affecting the shape of the growth curve for
      weight may be greater for same sex pairs.

PMID- 28520306
TI  - Sex differentials in unintentional injury mortality in relation to age at death.
AB  - Sex differentials in unintentional injury mortality were examined using death
      records for New York State residents that died as the result of an unintentional
      injury between the years 1984 and 1988 (n = 22,547). Male/female ratios were
      computed for nine age groups and for the four leading causes of unintentional
      injury death: motor vehicle incidents, falls, fire, and drowning. Male mortality
      is significantly higher than female mortality for all causes (P < 0.05). The age
      specific pattern of mortality varies among the four causes of death examined, but
      the age-specific pattern of male/female mortality ratios is consistent among all
      four causes. All four leading causes of unintentional injury death show a peak in
      relative male risk in young adulthood (usually between 15 and 24 years of age).
      This common peak may reflect increased risk associated behaviors of young males,
      including alcohol. Two causes of death, motor vehicle incidents and fire, show a
      second peak in relative male risk among the elderly (75+ years), perhaps
      reflecting sex differences in alcohol and tobacco use.

PMID- 28520307
TI  - Human Biology Council.

PMID- 28520308
TI  - Altitude and growth among the sherpas of the eastern Himalayas.
AB  - The results of the anthropometric survey of Sherpa children of both sexes (n =
      478) from high- and low-altitude areas in the eastern Himalayas are presented.
      The study reveals that growth is slower both more prolonged in the high-altitude
      Sherpas compared with growth at low altitude and that Sherpa children are the
      smallest of all the high-altitude populations considered here. Sexual dimorphism
      is not well defined during the earlier age periods. Our skinfold thickness data
      from the low-altitude Sherpas corroborate the centripetal distribution of fat
      found elsewhere.

PMID- 28520310
TI  - Editorial.

PMID- 28520309
TI  - Model fitting to early childhood length and weight data from the fels
      longitudinal study of growth.
AB  - Length and weight data from 3 months to 6 years of age from 466 participants in
      the Fels Longitudinal Study of Growth were used to fit the Jenss non-linear
      growth curve. Six (1%) of the Fels participants had extremely outlying values for
      length parameters, and 20 (4%) had outlying values for weight parameters. The
      general pattern in the outliers is for average or below average size in infancy,
      followed by unusually rapid growth or weight gain in childhood. This outlier
      pattern is associated with significantly higher mean stature or weight at 18
      years of age. The results for the majority of the participants are similar to
      those found in 229 children from the Harvard Growth Study, except for the non
      linear intercept for length and the linear intercept for weight. Significant sex
      differences have not previously been reported for Jenss parameters, perhaps
      because previous applications have used much smaller sample sizes.

PMID- 28520311
TI  - Estimation of total body water by bioelectrical impedance analysis in blacks.
AB  - Several differences exist between the body composition of blacks and whites. This
      study was designed to investigate the applicability of bioelectrical impedance
      analysis (BIA) in blacks, using prediction equations developed in whites. A
      multiple regression equation developed on 79 white adults, using deuterium oxide
      dilution space total body water (D2 O-TBW) as the reference method, was
      prospectively applied to 88 blacks aged 19-50 years. Although the regression line
      of D2 O-TBW on BIA-TBW was not significantly different from the line of identity
      (r = 0.98, SEE = 1.71 liters), mean TBW was significantly underestimated by 0.84
      liter. Other BIA equations from the literature also underestimated D2 O-TBW in
      blacks, except for an equation developed on a mixed black and white population.
      Multiple regression analysis on the data of the black and white subjects combined
      showed that race, offered as a separate independent variable, improved the
      correlation with D2 O-TBW slightly but significantly (P < 0.01). It was concluded
      that BIA may be valuable in the assessment of body composition in blacks as well
      as in whites. In this study a small underestimation of TBW occurred in blacks,
      using (BIA) equations from whites. This may be due to racial differences in body
      composition or to factors unrelated to ethnicity.

PMID- 28520312
TI  - Differentially delayed development in the hand-wrist skeletons of children with
      cystic fibrosis: Round versus tubular bones.
AB  - From a sample of 50 cystic fibrosis patients in whom a previous study had
      demosntrated a lack of statistical interdependence between disease severity and
      significant TW2-20 bone age delays, hand-wrist radiographs for a preadolescent
      subsample of 30 (14 females and 16 males, 7.4 to 13.0 years of age) are
      reassessed using the TW2 method to (1) elucidate any significant differences in
      maturational delays exhibited by the carpals and the tubular bones (radius, ulna,
      and short bones [RUS]) of the hand-wrist complex and (2) assess the relationships
      between the clinically derived measure of pulmonary disease severity,
      anthropometric indices of nutritional status, and the bone age delays in these
      two regions. Female and male carpal bone age delays, pulmonary disease severity
      scores, and weight/height2 differ significantly. However, both sexes exhibit
      significant mean TW2-carpal bone age delays, while mean TW2-RUS ages are either
      non-significantly delayed or advanced with respect to normative standards.
      Correlation and all-subsets multiple linear regression analyses reveal no
      significant interdependence or predictive relationships between clinically
      derived measures of pulmonary disease severity and anthropometric measures of
      nutritional complications and delayed skeletal maturation in either the carpals
      or tubular bones of the hand-wrist complex.

PMID- 28520313
TI  - Inheritance of longevity evinces no secular trend among members of six New
      England families born 1650-1874.
AB  - This study investigated the historical trend in resemblance between first-degree
      relatives for age at death. Data from genealogies of six New England families (N
      = 13,656) were divided into nine 25 year birth cohorts, 1650-1874, to test the
      hypothesis that familial influence on human longevity has changed during the past
      300 years. Heritability (h2 ) for longevity demonstrated no historical trend,
      whether calculated by regression of offspring's longevity on paternal, maternal,
      or mid-parental longevity or by intraclass correlations (t) among sibships.
      Ninety-five percent confidence intervals (C.I.) for h2 (additive genetic
      variance) were in the range 0.10-0.33 for parent-offspring regressions and 0.16
      0.22 based on mean of sibship regressed on mean of parents. Based on sibship t,
      the 95% C.I. for the upper limit to h2 (which includes variance contributions
      caused by dominance interactions and common developmental environment as well as
      additive genetic effects) was 0.33-0.41. In this socially elite sample, the
      statistical contribution of first-degree relatives to age at death has varied
      within a historically consistent range over the past 300 years, directly implying
      a persistent genetic influence on longevity. The magnitude of this influence with
      respect to additive genetic variance, about 10-30%, may overestimate h2 because
      of the elite nature of the sample. Nevertheless, these results support a genetic
      component to lifespan even though the majority of variation in human longevity is
      not explained by genetic factors.

PMID- 28520314
TI  - Twin study of digital dermatoglyphic traits: Investigation of heritability.
AB  - Digital patterns of a sample of monozygotic and dizygotic twins were analyzed to
      obtain heritability values for the four basic types of patterns: arch, tented
      arch, loops, and whorls. Loops have been separated according to their orientation
      radial or ulnar. To carry out this study, we used the Holzinger and Clark
      indices. The results show highest concordances for monozygotic twins except for
      ulnar loops of the left hand and radial ones of the right hand. Different values
      of heritability were found for the right and left hands, with finger I having the
      highest values.

PMID- 28520315
TI  - Adiposity and age of menarche in Hispanic women.
AB  - Women with increased adiposity have been shown to have earlier menarche. However,
      the association between menarche and body fat distribution has been
      controversial. The present study examined relationships between several
      anthropometric data and age at menarche in 2,494 women aged 25 to 74 years from
      the Hispanic Health and Nutrition Examination Survey. Early menarche was
      similarly related to adiposity as measured by body mass index (BMI), skinfolds
      representative of central adiposity (subscapular and iliac), and skinfolds
      representative of peripheral adiposity (triceps and calf). These relationships
      persisted after controlling for a variety of influences such as socioeconomic
      status; they were consistent in all three ethnic groups studied, but were
      significant only in Puerto Rican women. Ratios of central/peripheral skinfold
      measures were not associated with menarche. These analyses describe the
      relationship between early maturation and overall adiposity in three distinct
      Hispanic groups and reject a specific association between menarche and central
      body fat distribution.

PMID- 28520317
TI  - A Very Different Paradigm for Living Kidney Donor Risk.

PMID- 28520316
TI  - The Living Donor Collective: A Scientific Registry for Living Donors.
AB  - In the setting of an overall decline in living organ donation and new questions
      about long-term safety, a better understanding of outcomes after living donation
      has become imperative. Adequate information on outcomes important to donors may
      take many years to ascertain and may be evident only by comparing large numbers
      of donors with suitable controls. Previous studies have been unable to fully
      answer critical questions, primarily due to lack of appropriate controls,
      inadequate sample size, and/or follow-up duration that is too short to allow
      detection of important risks attributable to donation. The Organ Procurement and
      Transplantation Network does not follow donors long term and has no prospective
      control group with which to compare postdonation outcomes. There is a need to
      establish a national living donor registry and to prospectively follow donors
      over their lifetimes. In addition, there is a need to better understand the
      reasons many potential donors who volunteer to donate do not donate and whether
      the reasons are justified. Therefore, the US Health Resources and Services
      Administration asked the Scientific Registry of Transplant Recipients to
      establish a national registry to address these important questions. Here, we
      discuss the efforts, challenges, and opportunities inherent in establishing the
      Living Donor Collective.

PMID- 28520318
TI  - [Image of the month. A pediatric case of unilateral proptosis and cystic
      lymphangioma.]

PMID- 28520319
TI  - [How I treat... a neonatal Herpes simplex virus infection].
AB  - Neonatal herpes simplex virus infection is rare but important to recognize
      because of the major risk of sequelae or death. The diagnosis is mainly based on
      specific clinical and biological analyses. Aciclovir is the treatment of choice,
      duration of administration depending on the severity of the disease. A six-month
      treatment with suppressive-dose oral aciclovir is recommended to improve the
      child's prognosis. From a clinical case, we reviewed the literature to improve
      the management.

PMID- 28520320
TI  - [Pathergic postsurgical-induced Pyoderma gangrenosum].
AB  - Pyoderma gangrenosum (PG) is a rare pustular and ulcerative inflammatory disease
      belonging to the group of neutrophilic dermatoses. It is frequently associated
      with systemic immune diseases. In this context the PG can be exceptionally
      triggered by tissue trauma such as surgery (pathergy). We report the case of a
      patient with stabilized rheumatoid arthritis who developed aggressive and
      disseminated PG at all surgical wounds following an abdominal dermolipectomy
      associated with breast pexy. Systemic corticosteroid methylprednisolone allowed a
      rapid control of skin ulcerations. In the aftermath of an intervention, PG is
      often confused with a bacterial skin-necrotizing panniculitis. The recognition of
      the inflammatory nature of cutaneous symptoms is crucial to quickly start an
      immunosuppressive treatment and limit scarring sequelae. Our case also
      illustrates the need to consider any history of dysimmune inflammatory or
      oncohematological disease as a risk factor before surgery, even if the latter are
      stabilized.

PMID- 28520321
TI  - [Multifocal osteonecrosis revealing an antiphospholipid syndrome : case report].
AB  - This article illustrates the case of a 30-year-old woman presenting with
      multifocal osteonecrosis as the first symptom of a primary antiphospholipid
      syndrome. The association of multifocal osteonecrosis and primary
      antiphospholipid syndrome without any medical history of vascular thrombosis or
      pregnancy complications remains rare.

PMID- 28520322
TI  - [Psychological impact of out-of-hospital cardiopulmonary resuscitation (CPR) on
      the witness engaged in gestures of survival].
AB  - The occurrence of an unexpected sudden death puts the witnesses of this event in
      a situation of high emotional impact. The benefit to allow the families of
      victims to dispense the first resuscitation techniques has been emphasized.
      However, little data exist on the emotional impact of a cardio-respiratory arrest
      outside the hospital on the witness, who is often a close family member.
      Recently, we investigated the presence of psychological distress and the factors
      influencing it, in the active practice of basic resuscitation gestures by the
      witnesses guided by the operator 112. Resuscitation by a person not belonging to
      the medical corps seems not to be devoid of psychological impact. Indeed, the
      presence of psychological distress is observed for most of witnesses questioned 6
      to 10 days after the call but also 3 months later. This work highlights therefore
      the importance of identifying the coping strategies involved, in order to promote
      potentially beneficial strategies and limit the trauma associated with this type
      of event.

PMID- 28520323
TI  - [Asthma and obesity].
AB  - Asthma and obesity are both common diseases in western world. According to the
      data from our asthma clinic 20 % of our patients are obese and this rate
      increases up to 25 % in severe asthmatics included in the Belgian Severe Asthma
      national Registry. Alteration of thoracic mechanics contributes to greater
      symptom burden and poor asthma control in obese asthmatics. In particular the
      response to inhaled corticoids is attenuated. Weight loss results in a dramatic
      improvement in asthma control and should be a major goal in the asthma management
      of these patients.

PMID- 28520324
TI  - [Professional fatigue syndrome (burnout). Part 1 : identification by the general
      practitioner].
AB  - Burnout or professional fatigue syndrome has never been more talked about than in
      recent times. It is the result of exposure to a situation in which the strategies
      of the subject who are supposed to manage the stresses of the environment become
      outdated and inoperative. An imbalance is created between the demands and the
      material, operational and psychological resources to cope with them. Many health
      professions are confronted with the challenge of managing burnout. Among them,
      the general practitioner is very often on the front line. This paper is dedicated
      to him in priority. In its first part, it deals successively with the
      classification of the pathology (ICD-10 and DSM-5), its prevalence, its socio
      economic impacts, its clinical picture (three stages), its diagnosis (by clinic
      and questionnaires), its causes, its evolution (from denial to acceptance), and
      its long-term consequences in the absence of treatment.

PMID- 28520325
TI  - [Newborn infants' first outpatient visit].
AB  - The focus on outpatient follow-up of newborn infants increases as the duration of
      hospital stay after birth decreases. The first outpatient visit addresses the
      adequacy of the home transition. Appropriate feedings are checked. Sudden infant
      death syndrome prevention and security advices are reminded. Realisation of both
      neonatal dried blood screen and hearing test is confirmed, as well as planning of
      specific follow-up appointments. The physical exam will focus on red flags for
      diseases or malformations with a delayed presentation.

PMID- 28520326
TI  - [Bipressil(r) : first single-pill combination of bisoprolol and perindopril
      arginine].
AB  - In patients suffering from systemic arterial hypertension, coronary artery
      disease, or heart failure, beta-blockers and angiotensin-convertase enzyme
      inhibitors play a major therapeutic and preventive role. Coronary artery disease
      remains the leading cause of mortality in industrialized countries. Unless
      adapted preventive strategy, notably pharmacological interventions,
      cardiovascular events in these patients remain high. One reason for this relative
      failure is represented by non-adherence to treatment. A treatment consisting in
      an association in one pill of several different molecules should confer a higher
      treatment compliance and thus efficacy. This article describes the
      characteristics of the first available dual association between a cardioselective
      beta-blocker agent, bisoprolol, and an angiotensin-convertase enzyme inhibitor,
      perindopril arginine.

PMID- 28520327
TI  - [Importance of stopping some medications in case of gastrointestinal disturbances
      leading to dehydration].
AB  - This clinical case draws attention to the importance of stopping some medications
      in case of gastrointestinal disturbances that could induce dehydration. The
      latter can provoke an acute renal failure, which may lead to a toxic accumulation
      of these pharmacological agents and/or increase their nephrotoxicity. This may
      induce a vicious circle that is potentially dangerous and even fatal. Three
      pharmacological classes that are widely used in clinical practice are considered
      as examples, metformin, inhibitors of the renin-angiotensin system and
      nonsteroidal anti-inflammatory drugs. For each of them, the pathophysiology of
      the complication will be briefly discussed. Some patient risk profiles where
      caution is mandatory will be also emphasized.

PMID- 28520328
TI  - Identification and Localization of beta-D-Glucosidasefrom Two Typical Oenococcus
      oeni Strains.
AB  - beta-D-glucosidase (betaG) gene from Oenococcus oeni SD-2a and 31MBR was cloned,
      sequenced and analyzed, also intracellular betaG of the two strains was further
      localized. The results showed that betaG gene of the two strains was in high
      homology (> 99%) to reported betaG gene, confirming both strains possess betaG
      activity at the molecular level. Intracellular betaG of SD-2a is a mainly soluble
      protein, existing mostly in the cytoplasm and to some extent in the periplasm.
      While for 31MBR, intracellular betaG is mainly insoluble protein existing in the
      cytoplasmic membrane. This study provides basic information for further study of
      the metabolic mechanism of betaG from O. oeni SD-2a and 31MBR.

PMID- 28520329
TI  - Characterization of Staphylococcal Cassette Chromosome mec (SCCmec)in Methicillin
      Resistant Staphylococcus epidermidis Strains Isolatedfrom Biomaterial-Associated
      Infections and their Antibiotic Resistance Patterns.
AB  - This work aims to provide an insight into staphylococcal cassette chromosome mec
      elements and antibiotic resistance in clinical isolates of Staphylococcus
      epidermidis. The dominating type was SCCmec - IV. Fifteen isolates were assigned
      to SCCmec type III, two isolates to SCCmec type II. Most isolates were resistant
      to at least three of the non-beta-lactam antibiotics tested. None of the strains
      exhibited resistance to new generation antibiotics, such as daptomycin and
      linezolid. Also, none of these strains showed resistance to tigecycline and only
      four strains were resistant to rifampin i.e. antibiotics which are very efficient
      in treating biofilm-associated infections.

PMID- 28520330
TI  - Qualitative and Quantitative Characteristics of Selected Bacterial Groupsin
      Children with Inflammatory Bowel Diseases.
AB  - The aim of the study was evaluation of qualitative and quantitative changes in
      bacterial ecosystem in 109 children with inflammatory bowel diseases. Stools
      obtained from patients were analysed for selected bacteria and concentration of
      faecal inflammatory markers (calprotectin, lactoferrin, M2-PK). The number of
      selected microorganisms depends on the level of clinical activity of disease and
      is correlated with faecal concentration of inflammatory markers. Differences in
      microflora disturbance, observed in patients with Crohn's disease and ulcerative
      colitis, may suggest different causes of development of both pathologies.

PMID- 28520331
TI  - Cytotoxic and Bacteriostatic Activity of Nanostructured TiO(2) Coatings.
AB  - Nanostructures are structures, mainly synthetic (nanosurfaces, cylindrical
      nanotubes, and nanospheres), which range between 1-100 nm in at least one
      dimension and can be engineered to a wide range of physical properties. This
      paper aims to explore the bacteriostatic and cytotoxic characteristics of nano
      TiO(2) coated specimens of glass, stainless steel and ceramic with different
      thickness and roughness. The results show that stainless steel and glass
      specimens with a nano-TiO(2) coating thickness of 200 nm have a bacteriostatic
      effect of 97% and 100%, respectively after 30 minutes of UV exposure. Glass
      specimens with a nano-TiO(2) coating thickness of 750, 200 and 50 nm have a
      bacteriostatic effect of 86%, 93% and 100% after 60 minutes. Nano-TiO(2) coatings
      show a great bacteriostatic but not a cytotoxic effect, thus representing a
      valuable alternative for biomedical applications.

PMID- 28520333
TI  - Monitoring of Virulence Genes, Drug-Resistance in Campylobacter coli Isolatedfrom
      Golden Retrievers.
AB  - The investigation was performed on 75 of Golden Retriever puppies. Faecal samples
      were collected on the 42 day of the puppies life (control). Probiotic preparation
      was administered on 43 day of the puppies life and 10 days after the application
      of the probiotic, faecal samples were collected again (on 53 day of puppies
      life). All isolates of Campylobacter coli isolated prior to the administration of
      the probiotic were found to contain the cadF gene responsible for adhesion, as
      well as, the flaA gene influencing motility of the examined bacteria. Significant
      differences (P < 0.05) were recorded only in the case of enrofloxacin.

PMID- 28520332
TI  - Enteroviruses Associated with Aseptic Meningitis in Poland, 2011-2014.
AB  - A 4-year study (2011-2014) of patients with meningitis was performed. Out of the
      686 cerebrospinal fluid samples, 465 (67.8%) were positive for eneteroviruses
      using RT-PCR and out of 334 clinical samples, 216 (64.7%) were positive for
      enteroviruses using cell culture methods. The highest detection rate was observed
      in the summer and autumn. In total, 185 enteroviruses were identified by using
      neutralization test. Echovirus 6 and 30 were the most common (41.7% and 37.5%
      respectively). The highest frequency of neurological infections (32.7%) occurred
      in children aged 5-9 years, mostly males (63.9%).

PMID- 28520334
TI  - Kidney anatomy: three dimensional (3D) printed pelvicalyceal system models of the
      collector system improve the diagnosis and treatment of stone disease.

PMID- 28520335
TI  - PRISMA statement and PROSPERO.

PMID- 28520336
TI  - PDE-5 inhibitors should be used post radical prostatectomy as erection function
      rehabilitation? | Opinion: Yes.

PMID- 28520338
TI  - Re: Artificial urinary sphincter for urinary incontinence after radical
      prostatectomy: a historical cohort from 2004 to 2015.

PMID- 28520386
TI  - Pneumococcal vaccine--past, present and future.

PMID- 28520337
TI  - PDE-5 inhibitors should be used post radical prostatectomy as erection function
      rehabilitation? | Opinion: No.

PMID- 28520339
TI  - REPLY BY THE AUTHORS: Re: Artificial urinary sphincter for urinary incontinence
      after radical prostatectomy: a historical cohort from 2004 to 2015.

PMID- 28520387
TI  - Pneumococcal infection: update.

PMID- 28520388
TI  - Immunological mechanism in the pathogenesis of pneumococcal pneumonia and in the
      effectiveness of anti-pneumococcal vaccines.

PMID- 28520389
TI  - Characteristics and Differences in Pneumococcal Vaccines: 1. Polysaccharide
      vaccine.

PMID- 28520390
TI  - Characteristics and Differences in Pneumococcal Vaccines; 2. Pneumococcal
      conjugate vaccine.

PMID- 28520391
TI  - Reaction Layer Imaging Using Fluorescence Electrochemical Microscopy.
AB  - The chemical confinement of a pH sensitive fluorophore to a thin-reaction layer
      adjacent to an electrode surface is explored as a potentially innovative route to
      improving the spatial resolution of fluorescence electrochemical microscopy. A
      thin layer opto-electrochemical cell is designed, facilitating the visualization
      of a carbon fiber (diameter 7.0 MUm) electrochemical interface. Proton
      consumption is driven at the interface by the reduction of benzoquinone to
      hydroquinone and the resulting interfacial pH change is revealed using the
      fluorophore 8-hydoxypyrene-1,3,6-trisulfonic acid. It is demonstrated that the
      proton depletion zone may be constrained and controlled by the addition of a
      finite acid concentration to the system. Simulation of the resulting fluorescence
      intensity profiles is achieved on the basis of a finite difference model, with
      excellent agreement between the theoretical and experimental results.

PMID- 28520392
TI  - Gold Nanostar Enhanced Surface Plasmon Resonance Detection of an Antibiotic at
      Attomolar Concentrations via an Aptamer-Antibody Sandwich Assay.
AB  - A new sandwich assay for tetracycline (TC) involving a DNA aptamer and antibody
      pair is demonstrated in conjunction with gold nanostar (GNS) enhanced surface
      plasmon resonance (SPR) to achieve detection in the low attomolar range. GNS
      particles were covalently functionalized with the antibody probe (antiTC) and
      integrated into a surface sandwich assay in conjunction with a SPR gold chip
      modified with the TC-specific aptamer. After it was demonstrated that both
      affinity probes can bind simultaneously to TC, optimization of the assay was
      performed using either antiTC only or GNS-antiTC conjugates to interact with
      aptamer/TC complexes present on the chip surface. Target concentrations as low as
      10 aM could be detected using GNS-antiTC's, which was >103 times greater in
      performance than when using antiTC only. In addition, good selectivity was
      achieved with respect to other tetracycline derivative antibiotics, such as
      oxytetracycline (OTC) and chlortetracycline (CTC), both which are structurally
      similar to TC. As a demonstration of trace antibiotic analysis in environmental
      samples, the GNS enhanced sandwich assay was applied to analyze TC added to
      aliquots of local river water and the results validated by comparing to
      conventional high-performance liquid chromatography (HPLC) analysis.

PMID- 28520394
TI  - In Vitro Metabolic Engineering of Amorpha-4,11-diene Biosynthesis at Enhanced
      Rate and Specific Yield of Production.
AB  - In vitro metabolic engineering is an alternative approach to cell-based
      biosynthesis. It offers unprecedented flexibility for the study of biochemical
      pathways, thus providing useful information for the rational design and assembly
      of reaction modules. Herein, we took the advantage of in vitro metabolic
      engineering to initially gain insight into the regulatory network of a
      reconstituted amorpha-4,11-diene (AD) synthetic pathway. Guided by lin-log
      approximation, we rapidly identified the hitherto unrecognized inhibition of
      adenosine triphosphate (ATP) on both farnesyl pyrophosphate synthase (FPPS) and
      amorpha-4,11-diene synthase (ADS). Furthermore, the byproduct, pyrophosphate
      (PPi), potently inhibits ADS, but not FPPS. To lower the inhibition, an ATP
      recycling system and pyrophosphatase were used and resulted in a significant (~3
      fold) enhancement in the rate of AD production (~5.7 MUmol L-1 min-1). A
      coimmobilized multienzyme reaction system was then developed to recycle the
      enzymes. When inhibitory metabolites concentrations were reduced, the specific
      enzymatic yield of AD was further enhanced (>6-fold). This study demonstrated
      that mitigating the accumulation of inhibitory metabolites can result in higher
      yields of AD production by in vitro multienzymatic reactions.

PMID- 28520396
TI  - Simultaneous Online Monitoring of Multiple Reactions Using a Miniature Mass
      Spectrometer.
AB  - Advances in chemical sampling using miniature mass spectrometer technology are
      used to monitor slow reactions at a frequency of ca. 180 h-1 (on the Mini 12)
      with no sample carryover and with inline derivatization in the case of poorly
      ionizing compounds. Moreover, we demonstrate high reproducibility with a relative
      error of less than 10% for major components. Monitoring is enabled using a
      continuous-flow nanoelectrospray (CF-nESI) probe contained in a custom-built 3D
      printed rotary holder. The holder position is automatically set using a stepper
      motor controlled by a microcontroller. Reaction progress of up to six reactions,
      including hydrazone formation and Katritzky transamination, can be monitored
      simultaneously without carryover for several hours.

PMID- 28520395
TI  - Tricyclic Spirolactones as Modular TRPV1 Synthetic Agonists.
AB  - TRPV1 is a prominent signal integrator of the pain system, known to be activated
      by vanilloids, a family of endogenous and exogenous pain-evoking molecules,
      through the vanilloid-binding site (VBS). The extensive preclinical profiling of
      small molecule inhibitors provides intriguing evidence that TRPV1 inhibition can
      be a useful therapeutic approach. However, the dissimilarity of chemical species
      that activate TRPV1 creates a major obstacle to understanding the molecular
      mechanism of pain induction, which is viewed as a pivotal trait of the
      somatosensory system. Here, we establish the existence of a unique family of
      synthetic agonists that interface with TRPV1 through the VBS, containing none of
      the molecular domains previously believed to be required for this interaction.
      The overarching value obtained from our inquiry is the novel advancement of the
      existing TRPV1 activation model. These findings uncover new potential in the area
      of pain treatment, providing a novel synthetic platform.

PMID- 28520393
TI  - Universal and Quantitative Method To Evaluate Inhibitor Potency for Cysteinome
      Proteins Using a Nonspecific Activity-Based Protein Profiling Probe.
AB  - Recently, there have been a limited number of new, validated targets for small
      molecule drug discovery in the pharmaceutical industry. Although there are
      approximately 30 000 genes in the human genome, only 2% are targeted by currently
      approved small-molecule drugs. One reason that many targets remain neglected by
      drug discovery programs is the absence of biochemical assays enabling evaluation
      of the potency of inhibitors in a quantitative and high-throughput manner. To
      overcome this issue, we developed a biochemical assay to evaluate the potency of
      both reversible and irreversible inhibitors using a nonspecific thiol-labeling
      fluorescent probe. The assay can be applied to any targets with a cysteine
      residue in a pocket that can accommodate small-molecule ligands. By constructing
      a mathematical model, we showed that the potency of compounds can be
      quantitatively evaluated by performing an activity-based protein profiling assay.
      In addition, the validity of the theory was confirmed experimentally using
      epidermal growth factor receptor kinase as a model target. This approach provides
      an assay system for targets for which biochemical assays cannot be developed. Our
      approach can potentially not only expand the number of exploitable targets but
      also accelerate the lead optimization process by providing quantitative structure
      activity relationship information.

PMID- 28520397
TI  - Laser-Induced Graphene Layers and Electrodes Prevents Microbial Fouling and
      Exerts Antimicrobial Action.
AB  - Prevention of fouling on surfaces is a major challenge that broadly impacts
      society. Water treatment technologies, hospital infrastructure, and seawater
      pipes exemplify surfaces that are susceptible to biofouling. Here we show that
      laser-induced graphene (LIG) printed on a polyimide film by irradiation with a
      CO2 infrared laser under ambient conditions is extremely biofilm resistant while
      as an electrode is strongly antibacterial. We investigated the antibacterial
      activity of the LIG surface using LIG powder in suspension or deposited on
      surfaces, and its activity depended on the particle size and oxygen content.
      Remarkably, the antimicrobial effects of the surface were greatly amplified when
      voltages in the range of 1.1-2.5 were applied in an electrode configuration in
      bacterial solutions. The bactericidal mechanism was directly observed using
      microscopy and fast photography, which showed a rapid bacterial movement toward
      the LIG surface and subsequent bacterial killing. In addition, electrochemical
      generation of H2O2 was observed; however, the bacterial killing mechanism
      depended strongly on the physical and electrical contact of the bacterial cells
      to the surfaces. The anti-biofilm activity of the LIG surfaces and electrodes
      could lead to efficient protection of surfaces that are susceptible to biofouling
      in environmental applications by incorporating LIG onto the surfaces.

PMID- 28520399
TI  - Immunofluorescence Imaging Strategy for Evaluation of the Accessibility of DNA 5
      Hydroxymethylcytosine in Chromatins.
AB  - DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found
      in various mammalian cells. Immunofluorescence imaging analysis essentially
      provides visual pictures for the abundance and distribution of DNA 5hmC in single
      cells. However, nuclear DNA is usually wrapped around nucleosomes, packaged into
      chromatins, and further bound with many functional proteins. These
      physiologically relevant events would generate barriers to the anti-5hmC antibody
      to selectively recognize 5hmC in DNA. By taking advantage of these naturally
      generated barriers, here, we present a strategy to evaluate the accessibility of
      DNA 5hmC in chromatins in situ. We demonstrate that a few of the 5hmC sites in
      DNA are exposed or accessible to anti-5hmC antibody under nondenaturing
      conditions, suggesting that these 5hmC sites are not covered by functional DNA
      binding proteins in mouse embryonic stem cells. Consistently, these 5hmC foci
      were distributed in open euchromatin regions as revealed by the 4',6-diamidino-2
      phenylindole (DAPI) staining. By overexpressing TET1 catalytic domain
      (responsible for oxidation 5mC to produce 5hmC) in human MCF-7 cells, we observed
      a significant increase in accessible 5hmC along with an increase in total 5hmC
      sites. Collectively, by the use of the nondenaturing immunofluorescence imaging
      approach, we could obtain a visual landscape on the accessibility of DNA 5hmC in
      chromatins.

PMID- 28520400
TI  - Femtomole-Scale High-Throughput Screening of Protein Ligands with Droplet-Based
      Thermal Shift Assay.
AB  - There is a great demand to measure protein-ligand interactions in rapid and low
      cost way. Here, we developed a microfluidic droplet-based thermal shift assay
      (dTSA) system for high-throughput screening of small-molecule protein ligands.
      The system is composed of a nanoliter droplet array chip, a microfluidic droplet
      robot, and a real-time fluorescence detection system. Total 324 assays could be
      performed in parallel in a single chip with an 18 * 18 droplet array. The
      consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole
      scale), which is significantly reduced by over 3 orders of magnitude compared
      with those in 96- or 384-well plate-based systems. We also observed the
      implementation of TSA in nanoliter droplet format could substantially improve
      assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which
      can be ascribed to the enhanced thermal conduction in small volume reactors. The
      dTSA system was optimized by studying the effect of droplet volumes, as well as
      protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its
      potential in drug discovery, we applied the dTSA system in screening inhibitors
      of human thrombin with a commercial library containing 100 different small
      molecule compounds, and two inhibitors were successfully identified and
      confirmed.

PMID- 28520398
TI  - Multiple States of Nitrile Hydratase from Rhodococcus equi TG328-2: Structural
      and Mechanistic Insights from Electron Paramagnetic Resonance and Density
      Functional Theory Studies.
AB  - Iron-type nitrile hydratases (NHases) contain an Fe(III) ion coordinated in a
      characteristic "claw setting" by an axial cysteine thiolate, two equatorial
      peptide nitrogens, the sulfur atoms of equatorial cysteine-sulfenic and cysteine
      sulfinic acids, and an axial water/hydroxyl moiety. The cysteine-sulfenic acid is
      susceptible to oxidation, and the enzyme is traditionally prepared using butyric
      acid as an oxidative protectant. The as-prepared enzyme exhibits a complex
      electron paramagnetic resonance (EPR) spectrum due to multiple low-spin (S = 1/2)
      Fe(III) species. Four distinct signals can be assigned to the resting active
      state, the active state bound to butyric acid, an oxidized Fe(III)-bis(sulfinic
      acid) form, and an oxidized complex with butyric acid. A combination of
      comparison with earlier work, development of methods to elicit individual
      signals, and design and application of a novel density functional theory method
      for reproducing g tensors to unprecedentedly high precision was used to assign
      the signals. These species account for the previously reported EPR spectra from
      Fe-NHases, including spectra observed upon addition of substrates. Completely new
      EPR signals were observed upon addition of inhibitory boronic acids, and the
      distinctive g1 features of these signals were replicated in the steady state with
      the slow substrate acetonitrile. This latter signal constitutes the first EPR
      signal from a catalytic intermediate of NHase and is assigned to a key
      intermediate in the proposed catalytic cycle. Earlier, apparently contradictory,
      electron nuclear double resonance reports are reconsidered in the context of this
      work.

PMID- 28520401
TI  - Identification of GalNAc-Conjugated Antisense Oligonucleotide Metabolites Using
      an Untargeted and Generic Approach Based on High Resolution Mass Spectrometry.
AB  - Antisense oligonucleotides linked by phosphorothioates are an important class of
      therapeutics under investigation in various pharmaceutical companies. Antisense
      oligonucleotides may be coupled to high-affinity ligands (triantennary N-acetyl
      galactosamine = GalNAc) for hepatocyte-specific asialoglycoprotein receptors
      (ASGPR) to enhance uptake to hepatocytes and to increase potency. Since
      disposition and biotransformation of GalNAc-conjugated oligonucleotides is
      different from unconjugated oligonucleotides, appropriate analytical methods are
      required to identify main cleavage sites and degradation products of GalNAc
      conjugated and unconjugated oligonucleotides in target cells. A highly sensitive
      method was developed to identify metabolites of oligonucleotides using capillary
      flow liquid chromatography with column switching coupled to a high resolution
      Orbitrap Fusion mass spectrometer. Detection of GalNAc-conjugated
      oligonucleotides and their metabolites was achieved by combining full scan MS
      with two parallel MS2 experiments, one data-dependent scan and an untargeted MS2
      experiment (all ion fragmentation) applying high collision energy. In the all ion
      fragmentation scan, a diagnostic fragment originating from the phosphorothioate
      backbone (O2PS-: m/z 94.936) was formed efficiently upon collisional activation.
      Based on this fragment an accurate determination of metabolites of
      oligonucleotides was achieved, independent of their sequence or conjugation in an
      untargeted but highly selective manner. The method was effectively applied to
      investigate uptake and metabolism of GalNAc-conjugated oligonucleotides in
      incubations of primary rat hepatocytes; the elucidation of expected and
      unexpected degradation products was achieved in subnanomolar range.

PMID- 28520403
TI  - Integrated Strategy for Unknown EI-MS Identification Using Quality Control
      Calibration Curve, Multivariate Analysis, EI-MS Spectral Database, and Retention
      Index Prediction.
AB  - Compound identification using unknown electron ionization (EI) mass spectra in
      gas chromatography coupled with mass spectrometry (GC-MS) is challenging in
      untargeted metabolomics, natural product chemistry, or exposome research. While
      the total count of EI-MS records included in publicly or commercially available
      databases is over 900 000, efficient use of this huge database has not been
      achieved in metabolomics. Therefore, we proposed a "four-step" strategy for the
      identification of biologically significant metabolites using an integrated
      cheminformatics approach: (i) quality control calibration curve to reduce
      background noise, (ii) variable selection by hypothesis testing in principal
      component analysis for the efficient selection of target peaks, (iii) searching
      the EI-MS spectral database, and (iv) retention index (RI) filtering in
      combination with RI predictions. In this study, the new MS-FINDER spectral search
      engine was developed and utilized for searching EI-MS databases using mass
      spectral similarity with the evaluation of false discovery rate. Moreover, in
      silico derivatization software, MetaboloDerivatizer, was developed to calculate
      the chemical properties of derivative compounds, and all retention indexes in EI
      MS databases were predicted using a simple mathematical model. The strategy was
      showcased in the identification of three novel metabolites (butane-1,2,3-triol, 3
      deoxyglucosone, and palatinitol) in Chinese medicine Senkyu for quality
      assessment, as validated using authentic standard compounds. All tools and
      curated public EI-MS databases are freely available in the 'Computational MS
      based metabolomics' section of the RIKEN PRIMe Web site (
      http://prime.psc.riken.jp ).

PMID- 28520402
TI  - Catch and Release: Engineered Allosterically Regulated beta-Roll Peptides Enable
      On/Off Biomolecular Recognition.
AB  - Alternative scaffolds for biomolecular recognition are being developed to
      overcome some of the limitations associated with immunoglobulin domains. The
      repeat-in-toxin (RTX) domain is a repeat protein sequence that reversibly adopts
      the beta-roll secondary structure motif specifically upon calcium binding. This
      conformational change was exploited for controlled biomolecular recognition.
      Using ribosome display, an RTX peptide library was selected to identify binders
      to a model protein, lysozyme, exclusively in the folded state of the peptide.
      Several mutants were identified with low micromolar dissociation constants. After
      concatenation of the mutants, a 500-fold increase in the overall affinity for
      lysozyme was achieved leading to a peptide with an apparent dissociation constant
      of 65 nM. This mutant was immobilized for affinity chromatography experiments,
      and the on/off nature of the molecular recognition was demonstrated as the target
      is captured from a mixture in the presence of calcium and is released in the
      absence of calcium as the RTX peptides lose their beta-roll structure. This work
      presents the design of a new stimulus-responsive scaffold that can be used for
      environmentally responsive specific molecular recognition and self-assembly.

PMID- 28520404
TI  - Enzymatic Reactor with Trypsin Immobilized on Graphene Oxide Modified Polymer
      Microspheres To Achieve Automated Proteome Quantification.
AB  - Protein digestion and isotope labeling are two critical steps in proteome
      quantification. However, the conventional in-solution protocol unavoidably
      suffers from disadvantages such as time-consuming, low labeling efficiency, and
      tedious off-line manual operation, which might affect the quantification
      accuracy, reproducibility, and throughput. To address these problems, we
      developed a fully automated proteome quantification platform, in which an
      ultraperformance immobilized microreactor (upIMER) with graphene-oxide-modified
      polymer microspheres as the matrix was developed, to achieve not only the
      simultaneous protein digestion and 18O labeling, but also the online integration
      with nano-high-pressure liquid chromatography-electrospray ionization-tandem mass
      spectrometry (nanoHPLC-ESI-MS/MS). Compared to the conventional off-line
      protocols, such a platform exhibits obviously improved digestion and 18O labeling
      efficiency (only 8% peptides with missed cleavage sites, 99% labeling efficiency,
      and 2.5 min reaction time), leading to the increased quantification coverage,
      accuracy, precision and throughput. All the results demonstrated that our
      developed fully automated platform should provide new opportunities to improve
      the accuracy, reproducibility, and throughput for proteome quantification.

PMID- 28520405
TI  - Morphology-Driven Control of Metabolite Selectivity Using Nanostructure-Initiator
      Mass Spectrometry.
AB  - Nanostructure-initiator mass spectrometry (NIMS) is a laser desorption/ionization
      analysis technique based on the vaporization of a nanostructure-trapped liquid
      "initiator" phase. Here we report an intriguing relationship between NIMS surface
      morphology and analyte selectivity. Scanning electron microscopy and
      spectroscopic ellipsometry were used to characterize the surface morphologies of
      a series of NIMS substrates generated by anodic electrochemical etching. Mass
      spectrometry imaging was applied to compare NIMS sensitivity of these various
      surfaces toward the analysis of diverse analytes. The porosity of NIMS surfaces
      was found to increase linearly with etching time where the pore size ranged from
      4 to 12 nm with corresponding porosities estimated to be 7-70%. Surface
      morphology was found to significantly and selectively alter NIMS sensitivity. The
      small molecule (<2k Da) sensitivity was found to increase with increased
      porosity, whereas low porosity had the highest sensitivity for the largest
      molecules examined. Estimation of molecular sizes showed that this transition
      occurs when the pore size is <3* the maximum of molecular dimensions. While the
      origins of selectivity are unclear, increased signal from small molecules with
      increased surface area is consistent with a surface area restructuring-driven
      desorption/ionization process where signal intensity increases with porosity. In
      contrast, large molecules show highest signal for the low-porosity and small-pore
      size surfaces. We attribute this to strong interactions between the initiator
      coated pore structures and large molecules that hinder desorption/ionization by
      trapping large molecules. This finding may enable us to design NIMS surfaces with
      increased specificity to molecules of interest.

PMID- 28520406
TI  - Characterization of 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N
      [Methoxy(polyethylene glycerol)-2000] and Its Complex with Doxorubicin Using
      Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics.
AB  - Polyethylene glycol (PEG) lipid nanoparticles (LNPs) spontaneously assemble in
      water, forming uniformly sized nanoparticles incorporating drugs with prolonged
      blood clearance compared to drugs alone. Previously, 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-N-[methoxy(polyethylene glycerol)-2000] (DSPE-PEG2000) and
      several drug adducts, including doxorubicin, were analyzed by a combination of
      physical and molecular dynamic (MD) studies. In this study, a complete chemical
      shift assignment of DSPE-PEG2000 plus or minus doxorubicin was achieved using
      nuclear magnetic resonance (NMR), one-dimensional selective nuclear Overhauser
      spectroscopy (1D-selNOESY), NOESY, correlation spectroscopy (COSY), total
      correlated spectroscopy (TOCSY), heteronuclear single quantum coherence (HSQC),
      and HSQC-TOCSY. Chemical shift perturbation, titration, relaxation enhancement,
      and NOESY analysis combined with MD reveal detailed structural information at the
      atomic level, including the location of doxorubicin in the micelle, its binding
      constant, the hydrophilic shell organization, and the mobility of the PEG2000
      tail, demonstrating that NMR spectroscopy can characterize drug-DSPE-PEG2000
      micelles with molecular weights above 180 kDa. The MD study revealed that an
      initial spherical organization led to a more-disorganized oblate structure in an
      aqueous environment and agreed with the NMR study in the details of the fine
      structure, in which methyl group(s) of the stearic acid in the hydrophobic core
      of the micelle are in contact with the phosphate headgroup of the lipid. Although
      the molecular size of the LNP drug complex is about 180 kDa, atomic resolution
      can be achieved by NMR-based methods that reveal distinct features of the drug
      lipid interactions. Because many drugs have unfavorable blood clearance that may
      benefit from incorporation into LNPs, a thorough knowledge of their physical and
      chemical properties is essential to moving them into a clinical setting. This
      study provides an advanced basic approach that can be used to study a wide range
      of drug-LNP interactions.

PMID- 28520407
TI  - Controlling Configurational Isomerism in Three-Component Colloidal Hybrid
      Nanoparticles.
AB  - Colloidal hybrid nanoparticles are solution-dispersible constructs that join
      together multiple distinct nanoscale materials through direct solid-solid
      interfaces. Given their multifunctionality and synergistic properties that emerge
      from interfacial coupling, hybrid nanoparticles are of interest for applications
      in biomedical imaging, solar energy conversion, heterogeneous catalysis,
      nanophotonics, and beyond. High-order hybrid nanoparticles, which incorporate
      three or more nanocrystal domains, offer greater tunability and functional
      diversity relative to one or two-component nanoparticles. The multiple
      heterojunctions within these structures can facilitate complex electromagnetic
      coupling as well as cooperative surface processes. Additionally, these materials
      can be used as model systems for studying fundamental structure-property
      relationships at the nanoscale that arise from particle coupling and interfacial
      exchanges. Limiting these advances is the inability to synthesize hybrid
      nanoparticles with precise morphologies and geometries. High-order hybrid
      nanoparticles can adopt more than one configuration, and each unique arrangement
      will have different heterointerfaces and, accordingly, different functions.
      Seeded-growth methods are among the most effective methods for producing high
      quality hybrid nanoparticles. Engineering complex heterostructures using these
      stepwise reactions is in some ways conceptually analogous to the total synthesis
      of large organic molecules. However, unlike in molecular synthesis, the rules and
      guidelines that underpin the formation of hybrid nanoparticles are less
      understood. For example, when a third domain is added to a two-component
      heterodimer nanoparticle seed, several distinct types of hybrid nanoparticle
      products are possible, but only one is typically observed due to preferred growth
      at specific locations. The three-component heterotrimer products that
      preferentially form are not necessarily those that have the domain configurations
      and heterojunctions required to facilitate a targeted application. Different
      arrangements of the three nanoparticles that comprise a heterotrimer lead to
      distinct configurational isomers. Accordingly, understanding and controlling
      configurational isomerism in nanoparticle heterotrimers is foundational for
      engineering high-order hybrid nanostructures with targeted heterointerfaces,
      properties, and functionalities. This Account highlights recent insights into the
      pathways by which three-component nanoparticle heterotrimers form and how their
      configurations can be controlled and modified. In-depth microscopic
      investigations into the formation of heterotrimers by growing a third
      nanoparticle domain on a two-component heterodimer seed have revealed that in
      some cases indiscriminate nucleation first occurs on all exposed surfaces
      followed by surface-mediated migration and coalescence to the preferred
      interface. This insight helps to rationalize observed site-specific,
      chemoselective growth phenomena. Additionally, new approaches for directing
      growth in heterotrimer synthesis, such as protection-deprotection schemes
      inspired by organic chemistry, are becoming effective tools for constructing
      hybrid nanoparticles having nonpreferred domain configurations. Alternatives to
      traditional seeded-growth approaches are also emerging, including insertion
      reactions driven by saturation-precipitation processes and orthogonal
      transformations of preformed hybrid constructs using ion exchange. These and
      other recent advances are providing a powerful suite of synthetic tools that are
      anticipated to enable function-driven design of high-order hybrid nanoparticles
      having targeted properties and applications.

PMID- 28520408
TI  - Engineering and Characterization of Bacterial Nanocellulose Films as Low Cost and
      Flexible Sensor Material.
AB  - Some bacterial strains such as Komagataeibacter xylinus are able to produce
      cellulose as an extracellular matrix. In comparison to wood-based cellulose,
      bacterial cellulose (BC) holds interesting properties such as biodegradability,
      high purity, water-holding capacity, and superior mechanical and structural
      properties. Aiming toward improvement in BC production titer and tailored
      alterations to the BC film, we engineered K. xylinus to overexpress partial and
      complete bacterial cellulose synthase operon that encodes activities for BC
      production. The changes in cell growth, end metabolite, and BC production titers
      from the engineered strains were compared with the wild-type K. xylinus. Although
      there were no significant differences between the growth of wild-type and
      engineered strains, the engineered K. xylinus strains demonstrated faster BC
      production, generating 2-4-fold higher production titer (the highest observed
      titer was obtained with K. xylinus-bcsABCD strain producing 4.3 +/- 0.46 g/L BC
      in 4 days). The mechanical and structural characteristics of cellulose produced
      from the wild-type and engineered K. xylinus strains were analyzed with a stylus
      profilometer, in-house built tensile strength measurement system, a scanning
      electron microscope, and an X-ray diffractometer. Results from the profilometer
      indicated that the engineered K. xylinus strains produced thicker BC films (wild
      type, 5.1 MUm, and engineered K. xylinus strains, 6.2-10.2 MUm). Scanning
      electron microscope revealed no principal differences in the structure of the
      different type BC films. The crystallinity index of all films was high (from 88.6
      to 97.5%). All BC films showed significant piezoelectric response (5.0-20 pC/N),
      indicating BC as a promising sensor material.

PMID- 28520409
TI  - FeCo-Anchored Reduced Graphene Oxide Framework-Based Soft Composites Containing
      Carbon Nanotubes as Highly Efficient Microwave Absorbers with Excellent Heat
      Dissipation Ability.
AB  - Conducting polymer composites containing ferromagnetic grafted-graphene
      derivatives are already appreciated for their lightweight, flexibility, and cost
      effectiveness in terms of microwave absorption. To further leverage the said
      properties of this wonder material, we propose a highly efficient replacement by
      blending conducting multiwall carbon nanotube (MWCNT) and FeCo anchored covalent
      cross-linked reduced graphene oxide (rGO) with poly(vinylidene fluoride) (PVDF).
      Interconnected conducting network of MWCNTs introduces higher electrical
      conductivity in the blend which is essential for microwave absorption. FeCo
      anchored porous interconnected rGO framework was designed via solvent-mediated in
      situ coreduction in the presence of Fe(II) and Co(II) precursors. Resulting cross
      linked-rGO/FeCo displays fascinating coexistence of ferromagnetism and conducting
      dielectric behavior, while largely preserving the robust 3D porous interconnected
      structure. Coupled with conducting MWCNTs, diamine cross-linked rGO/FeCo in a
      soft polymer matrix yields remarkably high total shielding effectiveness (SET) of
      -41.2 dB at 12 GHz, for a meager 10 wt % filler content. In addition, the
      composite materials display efficient heat dissipation abilities in conjunction
      with the trend in their thermal conductivities. This new-age microwave-absorbing
      material, powered by multifunctionality and tunable magnetodielectric properties,
      henceforth offers an amendable, cost-effective replacement to the existing
      solutions.

PMID- 28520410
TI  - Proteolytically Stable Cyclic Decapeptide for Breast Cancer Cell Targeting.
AB  - Starting with a previously reported linear breast cancer targeting decapeptide
      WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue
      cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one d-amino
      acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by
      the noncancerous cells compared to the linear peptide with two d-amino acids (x
      and k), and was stable toward proteolytic degradation. When immobilized on gold
      microcantilever surface, the cyclic peptide was able to capture breast cancer
      cells specifically and sense samples with >=25 cancer cells/mL. Animal studies
      using mice carrying orthotopic breast MDA-MB-231 tumors showed that the cyclic
      peptide preferentially accumulates in tumor (2 h after injection) and is rapidly
      cleared from all other organs except kidneys and liver. The study highlights the
      discovery of a novel proteolytically stable cyclic peptide that can be used for
      targeted drug delivery or for enumerating circulating breast tumor cells.

PMID- 28520411
TI  - Alignment-Based Prediction of Sites of Metabolism.
AB  - Prediction of metabolically labile atom positions in a molecule (sites of
      metabolism) is a key component of the simulation of xenobiotic metabolism as a
      whole, providing crucial information for the development of safe and effective
      drugs. In 2008, an exploratory study was published in which sites of metabolism
      were derived based on molecular shape- and chemical feature-based alignment to a
      molecule whose site of metabolism (SoM) had been determined by experiments. We
      present a detailed analysis of the breadth of applicability of alignment-based
      SoM prediction, including transfer of the approach from a structure- to ligand
      based method and extension of the applicability of the models from cytochrome
      P450 2C9 to all cytochrome P450 isozymes involved in drug metabolism. We evaluate
      the effect of molecular similarity of the query and reference molecules on the
      ability of this approach to accurately predict SoMs. In addition, we combine the
      alignment-based method with a leading chemical reactivity model to take
      reactivity into account. The combined model yielded superior performance in
      comparison to the alignment-based approach and the reactivity models with an
      average area under the receiver operating characteristic curve of 0.85 in cross
      validation experiments. In particular, early enrichment was improved, as
      evidenced by higher BEDROC scores (mean BEDROC = 0.59 for alpha = 20.0, mean
      BEDROC = 0.73 for alpha = 80.5).

PMID- 28520413
TI  - Temporal Characteristics of Brown Carbon over the Central Indo-Gangetic Plain.
AB  - Recent global models estimate that light absorption by brown carbon (BrC) in
      several regions of the world is ~30-70% of that due to black carbon (BC). It is,
      therefore, important to understand its sources and characteristics on temporal
      and spatial scales. In this study, we conducted semicontinuous measurements of
      water-soluble organic carbon (WSOC) and BrC using particle-into-liquid sampler
      coupled with a liquid waveguide capillary cell and total organic carbon analyzer
      (PILS-LWCC-TOC) over Kanpur (26.5 degrees N, 80.3 degrees E, 142 m amsl) during a
      winter season (December 2015 to February 2016). In addition, mass concentrations
      of organic and inorganic aerosol and BC were also measured. Diurnal variability
      in the absorption coefficient of BrC at 365 nm (babs_365) showed higher values
      (35 +/- 21 Mm-1) during late evening to early morning hours and was attributed to
      primary emissions from biomass burning (BB) and fossil fuel burning (FFB). The
      babs_365 reduced by more than 80% as the day progressed, which was ascribed to
      photo bleaching/volatilization of BrC and/or due to rising boundary layer height.
      Further, diurnal variability in the ratios of babs_405/babs_365 and
      babs_420/babs_365 suggests that the BrC composition was not uniform throughout a
      day. WSOC exhibited a strong correlation with babs_365 (slope = 1.22 +/- 0.007,
      r2 = 0.70, n = 13 265, intercept = -0.69 +/- 0.17), suggesting the presence of a
      significant but variable fraction of chromophores. Mass absorption efficiency
      (MAE) values of WSOC ranged from 0.003 to 5.26 m2 g-1 (1.16 +/- 0.60) during the
      study period. Moderate correlation (r2 = 0.50, slope = 1.58 +/- 0.019, n = 6471)
      of babs_365 was observed with the semivolatile oxygenated organic aerosols (SV
      OOA) fraction of BB resolved from positive matrix factorization (PMF) analysis of
      organic mass spectral data obtained from a high-resolution time-of-flight aerosol
      mass spectrometer (HR-ToF-AMS). The low-volatility OOA (LV-OOA) fraction of BB
      had a similar correlation to babs_365 (r2 = 0.54, slope = 0.38 +/- 0.004, n =
      6471) but appears to have a smaller contribution to the absorption.

PMID- 28520414
TI  - Structural and Magnetic Transitions in CaCo3V4O12 Perovskite at Extreme
      Conditions.
AB  - We investigated the structural, vibrational, magnetic, and electronic properties
      of the recently synthesized CaCo3V4O12 double perovskite with the high-spin (HS)
      Co2+ ions in a square-planar oxygen coordination at extreme conditions of high
      pressures and low temperatures. The single-crystal X-ray diffraction and Raman
      spectroscopy studies up to 60 GPa showed a conservation of its cubic crystal
      structure but indicated a crossover near 30 GPa. Above 30 GPa, we observed both
      an abnormally high "compressibility" of the Co-O bonds in the square-planar
      oxygen coordination and a huge anisotropic displacement of HS-Co2+ ions in the
      direction perpendicular to the oxygen planes. Although this effect is reminiscent
      of a continuous HS -> LS transformation of the Co2+ ions, it did not result in
      the anticipated shrinkage of the cell volume because of a certain "stiffing" of
      the bonds of the Ca and V cations. We verified that the oxidation states of all
      the cations did not change across this crossover, and hence, no charge-transfer
      effects were involved. Consequently, we proposed that CaCo3V4O12 could undergo a
      phase transition at which the large HS-Co2+ ions were pushed out of the oxygen
      planes because of lattice compression. The antiferromagnetic transition in
      CaCo3V4O12 at 100 K was investigated by neutron powder diffraction at ambient
      pressure. We established that the magnetic moments of the Co2+ ions were aligned
      along one of the cubic axes, and the magnetic structure had a 2-fold periodicity
      along this axis, compared to the crystallographic one.

PMID- 28520412
TI  - Identification of the Ferredoxin-Binding Site of a Ferredoxin-Dependent
      Cyanobacterial Nitrate Reductase.
AB  - An in silico model for the 1:1 ferredoxin (Fd)/nitrate reductase (NR) complex,
      using the known structure of Synechocystis sp. PCC 6803 Fd and the in silico
      model of Synechococcus sp. PCC 7942 NR, is used to map the interaction sites that
      define the interface between Fd and NR. To test the electrostatic interactions
      predicted by the model complex, five positively charged NR amino acids (Arg43,
      Arg46, Arg197, Lys201, and Lys614) and a negatively charged amino acid (Glu219)
      were altered using site-directed mutagenesis and characterized by activity
      measurements, metal analysis, and electron paramagnetic resonance (EPR) studies.
      All of the charge replacement variants retained wild-type levels of activity with
      reduced methyl viologen (MV), but a significant decrease in activity was observed
      for the R43Q, R46Q, K201Q, and K614Q variants when reduced Fd served as the
      electron donor. EPR analysis as well as the Fe and Mo analyses showed that loss
      of activity observed with these variants was not the consequence of perturbation
      of the Mo center or [4Fe-4S] cluster. Therefore, the loss of the Fd-linked
      specific activity observed with these variants can be explained only by invoking
      a role for Arg43, Arg46, Lys201, and Lys614 in Fd binding. The R43Q, R46Q, K201Q,
      and K614Q NR variants also showed a decreased binding affinity for Fd, compared
      to that of wild-type NR, supporting a key role of these four positively charged
      residues in the productive binding of Fd.

PMID- 28520415
TI  - Design and Synthesis of Soluble and Cell-Permeable PI3Kdelta Inhibitors for Long
      Acting Inhaled Administration.
AB  - PI3Kdelta is a lipid kinase that is believed to be important in the migration and
      activation of cells of the immune system. Inhibition is hypothesized to provide a
      powerful yet selective immunomodulatory effect that may be beneficial for the
      treatment of conditions such as asthma or rheumatoid arthritis. In this work, we
      describe the identification of inhibitors based on a thiazolopyridone core
      structure and their subsequent optimization for inhalation. The initially
      identified compound (13) had good potency and isoform selectivity but was not
      suitable for inhalation. Addition of basic substituents to a region of the
      molecule pointing to solvent was tolerated (enzyme inhibition pIC50 > 9), and by
      careful manipulation of the pKa and lipophilicity, we were able to discover
      compounds (20b, 20f) with good lung retention and cell potency that could be
      taken forward to in vivo studies where significant target engagement could be
      demonstrated.

PMID- 28520416
TI  - Experimental and Theoretical Evaluation of the Stability of True MOF Polymorphs
      Explains Their Mechanochemical Interconversions.
AB  - We provide the first combined experimental and theoretical evaluation of how
      differences in ligand structure and framework topology affect the relative
      stabilities of isocompositional (i.e., true polymorph) metal-organic frameworks
      (MOFs). We used solution calorimetry and periodic DFT calculations to analyze the
      thermodynamics of two families of topologically distinct polymorphs of zinc
      zeolitic imidazolate frameworks (ZIFs) based on 2-methyl- and 2-ethylimidazolate
      linkers, demonstrating a correlation between measured thermodynamic stability and
      density, and a pronounced effect of the ligand substituent on their stability.
      The results show that mechanochemical syntheses and transformations of ZIFs are
      consistent with Ostwald's rule of stages and proceed toward thermodynamically
      increasingly stable, more dense phases.

PMID- 28520417
TI  - Correction to Evaluating the Role of Multidrug Resistance Protein 3 (MDR3)
      Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals.

PMID- 28520419
TI  - Single Particle Tracking: From Theory to Biophysical Applications.
AB  - After three decades of developments, single particle tracking (SPT) has become a
      powerful tool to interrogate dynamics in a range of materials including live
      cells and novel catalytic supports because of its ability to reveal dynamics in
      the structure-function relationships underlying the heterogeneous nature of such
      systems. In this review, we summarize the algorithms behind, and practical
      applications of, SPT. We first cover the theoretical background including
      particle identification, localization, and trajectory reconstruction. General
      instrumentation and recent developments to achieve two- and three-dimensional
      subdiffraction localization and SPT are discussed. We then highlight some
      applications of SPT to study various biological and synthetic materials systems.
      Finally, we provide our perspective regarding several directions for future
      advancements in the theory and application of SPT.

PMID- 28520418
TI  - Polycyclic Furanobutenolide-Derived Cembranoid and Norcembranoid Natural
      Products: Biosynthetic Connections and Synthetic Efforts.
AB  - The polycyclic furanobutenolide-derived cembranoid and norcembranoid natural
      products are a family of congested, stereochemically complex, and extensively
      oxygenated polycyclic diterpenes and norditerpenes. Although the elegant
      architectures and biological activity profiles of these natural products have
      captured the attention of chemists since the isolation of the first members of
      the family in the 1990s, the de novo synthesis of only a single polycyclic
      furanobutenolide-derived cembranoid and norcembranoid has been accomplished. This
      article begins with a brief discussion of the proposed biosyntheses and
      biosynthetic connections among the polycyclic furanobutenolide-derived
      cembranoids and norcembranoids and then provides a comprehensive review of the
      synthetic efforts toward each member of the natural product family, including
      biomimetic, semisynthetic, and de novo synthetic strategies. This body of
      knowledge has been gathered to provide insight into the reactivity and
      constraints of these compact and highly oxygenated polycyclic structures, as well
      as to offer guidance for future synthetic endeavors.

PMID- 28520420
TI  - Local Descriptors of Dynamic and Nondynamic Correlation.
AB  - Quantitatively accurate electronic structure calculations rely on the proper
      description of electron correlation. A judicious choice of the approximate
      quantum chemistry method depends upon the importance of dynamic and nondynamic
      correlation, which is usually assesed by scalar measures. Existing measures of
      electron correlation do not consider separately the regions of the Cartesian
      space where dynamic or nondynamic correlation are most important. We introduce
      real-space descriptors of dynamic and nondynamic electron correlation that admit
      orbital decomposition. Integration of the local descriptors yields global numbers
      that can be used to quantify dynamic and nondynamic correlation. Illustrative
      examples over different chemical systems with varying electron correlation
      regimes are used to demonstrate the capabilities of the local descriptors. Since
      the expressions only require orbitals and occupation numbers, they can be readily
      applied in the context of local correlation methods, hybrid methods, density
      matrix functional theory, and fractional-occupancy density functional theory.

PMID- 28520421
TI  - Examining the Feasibility of Using Free Energy Perturbation (FEP+) in Predicting
      Protein Stability.
AB  - The importance of engineering protein stability is well-known and has the
      potential to impact many fields ranging from pharmaceuticals to food sciences.
      Engineering proteins can be both a time-consuming and expensive experimental
      process. The use of computation is a potential solution to mitigating some of the
      time and expenses required to engineer a protein. This process has been
      previously hindered by inaccurate force fields or energy equations and slow
      computational processors; however, improved software and hardware have made this
      goal much more attainable. Here we find that Schrodinger's new FEP+, although
      still imperfect, proves more successful in predicting protein stability than
      other simpler methods of investigation. This increased accuracy comes at a cost
      of computational time and resources when compared to simpler methods. This work
      adds to the initial testing of FEP+ by offering options for more accurately
      predicting protein stability in an efficient manner.

PMID- 28520423
TI  - Interstitial Bismuth Atoms in Icosahedral Rhodium Cages: Syntheses,
      Characterizations, and Molecular Structures of the [Bi@Rh12(CO)27]3-,
      [(Bi@Rh12(CO)26)2Bi]5-, [Bi@Rh14(CO)27Bi2]3-, and [Bi@Rh17(CO)33Bi2]4- Carbonyl
      Clusters.
AB  - The reaction of [Rh7(CO)16]3- with BiCl3 under N2 and at room temperature results
      in the formation of the new heterometallic [Bi@Rh12(CO)27]3- cluster in high
      yields. Further controlled addition of BiCl3 leads first to the formation of the
      dimeric [(Bi@Rh12(CO)26)2Bi]5- and the closo-[Bi@Rh14(CO)27Bi2]3- species in low
      yields, and finally, to the [Bi@Rh17(CO)33Bi2]4- cluster. All clusters were
      spectroscopically characterized by IR and electrospray ionization mass
      spectrometry, and their molecular structures were fully determined by X-ray
      diffraction studies. Notably, they represent the first examples of Bi atoms
      interstitially lodged in metallic cages that, in this specific case, are all
      based on an icosahedral geometry. Moreover, [Bi@Rh14(CO)27Bi2]3- forms an
      exceptional network of infinite zigzag chains in the solid state, thanks to
      intermolecular Bi-Bi distances.

PMID- 28520422
TI  - Global Land Use Regression Model for Nitrogen Dioxide Air Pollution.
AB  - Nitrogen dioxide is a common air pollutant with growing evidence of health
      impacts independent of other common pollutants such as ozone and particulate
      matter. However, the worldwide distribution of NO2 exposure and associated
      impacts on health is still largely uncertain. To advance global exposure
      estimates we created a global nitrogen dioxide (NO2) land use regression model
      for 2011 using annual measurements from 5,220 air monitors in 58 countries. The
      model captured 54% of global NO2 variation, with a mean absolute error of 3.7
      ppb. Regional performance varied from R2 = 0.42 (Africa) to 0.67 (South America).
      Repeated 10% cross-validation using bootstrap sampling (n = 10,000) demonstrated
      a robust performance with respect to air monitor sampling in North America,
      Europe, and Asia (adjusted R2 within 2%) but not for Africa and Oceania (adjusted
      R2 within 11%) where NO2 monitoring data are sparse. The final model included 10
      variables that captured both between and within-city spatial gradients in NO2
      concentrations. Variable contributions differed between continental regions, but
      major roads within 100 m and satellite-derived NO2 were consistently the
      strongest predictors. The resulting model can be used for global risk assessments
      and health studies, particularly in countries without existing NO2 monitoring
      data or models.

PMID- 28520424
TI  - Insights on the Reactivity of Terminal Phosphanido Metal Complexes toward
      Activated Alkynes from Theoretical Computations.
AB  - Herein we present a theoretical study on the reaction of [Re(PPh2) (CO)3(phen)]
      (phen = 1,10-phenanthroline) and [Re(PPh2) (CO)3(bipy)] (bipy = 2,2'-bipyridine)
      toward methyl propiolate. In agreement with experimental results for the phen
      ligand, the coupling of the substituted acetylenic carbon with the nonsubstituted
      ortho carbon of the phen ligand is the preferred route from both kinetic and
      thermodynamic viewpoints with a Gibbs energy barrier of 18.8 kcal/mol and an
      exoergicity of 11.1 kcal/mol. There are other two routes, the insertion of the
      acetylenic fragment into the P-Re bond and the coupling between the substituted
      acetylenic carbon and a carbonyl ligand in cis disposition, which are kinetically
      less favorable than the preferred route (by 2.8 and 1.9 kcal/mol, respectively).
      Compared with phen, the bipy ligand shows less electrophilic character and also
      less pi electron delocalization due to the absence of the fused ring between the
      two pyridine rings. As a consequence, the route involving the coupling with a
      carbonyl ligand starts to be kinetically competitive, whereas the product of the
      attack to bipy is still the most stable and would be the one mainly obtained
      after spending enough time to reach thermal equilibrium.

PMID- 28520425
TI  - Furan and Lactam Jadomycin Biosynthetic Congeners Isolated from Streptomyces
      venezuelae ISP5230 Cultured with Nepsilon-Trifluoroacetyl-l-lysine.
AB  - Angucycline antibiotics are composed of a classical four-ring angularly linked
      polyaromatic backbone. Differential cyclization chemistry of the A- and B-rings
      in jadomycin biosynthesis led to the discovery of two new furan analogues, while
      oxidation led to a ring-opened form of the jadomycin Nepsilon-trifluoroacetyl-l
      lysine (TFAL) congener. The compounds were isolated from Streptomyces venezuelae
      ISP5230 cultures grown with TFAL. Biosynthetic incorporation using d-[1-13C]
      glucose in cultures enabled the unambiguous assignment of the aldehyde, alcohol,
      and amide functionalities present in these new congeners through NMR
      spectroscopy. Tandem mass spectrometry analysis of cultures grown with 15Nalpha-
      or 15Nepsilon-lysine demonstrated the incorporation of Nalpha exclusively into
      the angucycline backbone, contrasting results with ornithine [J. Am. Chem. Soc.
      2015, 137, 3271]. Compounds were evaluated against antimicrobial and cancer cell
      panels and found to possess good activity against Gram-positive bacteria.

PMID- 28520427
TI  - Kinetic Monte Carlo Modeling of Charge Carriers in Organic Electronic Devices:
      Suppression of the Self-Interaction Error.
AB  - Kinetic Monte Carlo (KMC) simulations have emerged as an important tool to help
      improve the efficiency of organic electronic devices by providing a better
      understanding of their device physics. In the KMC simulation of an organic
      device, the reliability of the results depends critically on the accuracy of the
      chosen charge-transfer rates, which are themselves strongly influenced by the
      site-energy differences. These site-energy differences include components coming
      from the electrostatic forces present in the system, which are often evaluated
      through electric potentials described by the Poisson equation. Here we show that
      the charge-carrier self-interaction errors that appear when evaluating the site
      energy differences can lead to unreliable simulation results. To eliminate these
      errors, we propose two approaches that are also found to reduce the impact of
      finite-size effects. As a consequence, reliable results can be obtained at
      reduced computational costs. The proposed methodologies can be extended to other
      device simulation techniques as well.

PMID- 28520426
TI  - Reconsideration of the Rheology of Silica Filled Natural Rubber Compounds.
AB  - There is substantial progress along with giant debate in reinforcement mechanisms
      in relation to structured filler network and heterogeneously retarded polymer
      dynamics, while the dissipation behaviors have never been clarified for
      nanoparticle filled polymers. Herein dynamic rheological behaviors of silica
      filled natural rubber were investigated. Master curves of linear rheology in the
      hydrodynamic regime and those of the nonlinear Payne effect at a predetermined
      frequency were created, disclosing a leading role of dynamically retarded bulk
      rubbery phase to the hydrodynamic regime and a leading role of molecular
      disentanglement in the bulk phase to the Payne effect. The methodology is able to
      account for both reinforcement and dissipation of the compounds as a function of
      filler content. Furthermore, a frequency-dependent hydrodynamic to non
      hydrodynamic transition is revealed, revealing the importance of the relaxation
      of chains in the bulk phase to both reinforcement and dissipation of the
      compounds. It is suggested that the dynamics of the bulk phase play a critical
      role for the rheology in the hydrodynamic regime while the fractal filler
      aggregates become dominative only in the terminal non-hydrodynamic regime where
      the bulk phase relaxes sufficiently.

PMID- 28520429
TI  - Raman Radial Mode Revealed from Curved Graphene.
AB  - One of the unsolved fundamental issues of graphene is establishing an appropriate
      way to discern layers of graphene structures. We report a simple methodology to
      analyze graphene structures using Raman signals in the range of ~100 to ~500 cm-1
      comprising clear 118 or 175 cm-1 peaks. We demonstrate that the low-energy
      signals on Raman spectra of plasma-seeded grown graphene sheets originated from
      nanocurvature (c) of mono- (175 and 325-500 cm-1 signals) (c ~ 1 nm) and bilayer
      (118 cm-1 peak) (c ~ 2 nm) graphene with Raman simulations, based on Raman radial
      mode (RM) Eigen vectors. Our RM model provides a standard way of identifying and
      evaluating graphene structures.

PMID- 28520428
TI  - Cyclic Diarylheptanoids from Corylus avellana Green Leafy Covers: Determination
      of Their Absolute Configurations and Evaluation of Their Antioxidant and
      Antimicrobial Activities.
AB  - The methanol extract of the leafy covers of Corylus avellana, source of the
      Italian PGI (protected geographical indication) product "Nocciola di Giffoni",
      afforded two new cyclic diarylheptanoids, giffonins T and U (2 and 3), along with
      two known cyclic diarylheptanoids, a quinic acid, flavonoid-, and citric acid
      derivatives. The structures of giffonins T and U were determined as highly
      hydroxylated cyclic diarylheptanoids by 1D and 2D NMR experiments. Their relative
      configurations were assigned by a combined quantum mechanical/NMR approach,
      comparing the experimental 13C/1H NMR chemical shift data and the related
      predicted values. The absolute configurations of carpinontriol B (1) and
      giffonins T and U (2 and 3) were assigned by comparison of their experimental
      electronic circular dichroism curves with the TDDFT-predicted curves. The ability
      of the compounds to inhibit the lipid peroxidation induced by H2O2 and H2O2/Fe2+
      was determined by measuring the concentration of thiobarbituric acid reactive
      substances. Furthermore, the antimicrobial activity of the methanol extract of
      leafy covers of C. avellana and of the isolated compounds against the Gram
      positive strains Bacillus cereus and Staphylococcus aureus and the Gram-negative
      strains Escherichia coli and Pseudomonas aeruginosa was evaluated. Carpinontriol
      B (1) and giffonin U (3) at 40 MUg/disk caused the formation of zones of
      inhibition.

PMID- 28520431
TI  - Anomalous Behavior of Ultra-Low-Amplitude Capillary Waves. A Glimpse of the
      Viscoelastic Properties of Interfacial Water?
AB  - We investigate, both theoretically and by a differential interferometric
      technique, the behavior of large-wavelength capillary waves (of the order of 10-4
      m) selectively excited at the surface of drops and bubbles with typical
      eigenfrequencies of the order of 102 Hz. The resonance peaks of gas bubbles or
      hydrocarbon drops in water (radius less than 1 mm) highlight anomalously small
      dissipation in the region of ultralow (sub-nanometric) oscillation amplitudes,
      reaching a plateau at higher amplitudes. This is in sharp contrast to the usual
      oscillating systems, where an anomalous behavior holds at large amplitudes alone.
      Dissipation is strongly dependent on the excited vibrational modes and, in spite
      of remarkable numerical differences, water-vapor and water-hydrocarbon interfaces
      exhibit the same overall trend. A phenomenological model was developed, based on
      the assumption that water possesses a threshold viscoelasticity, above which it
      behaves like a regular viscous fluid. The well-known Deborah number was then
      estimated within the anomalous region and found to lie in the range of
      viscoelastic fluids. In agreement with previous studies of nanohydrodynamics
      (e.g., atomic force microscopy measurements with sub-nanometric tip motions), the
      present one lends support to the idea that every self-aggregating fluid exhibits
      yield stress behavior, including classical Newtonian fluids like water. The
      essential requirement is that the applied perturbation lie below a critical
      threshold, above which viscous behavior is recovered. Our differential
      interferometric technique seems particularly suitable for this type of studies,
      as it allows measurement of long-wavelength capillary waves with sub-nanometric
      resolution on the oscillation amplitudes.

PMID- 28520430
TI  - Fluorescence Dynamics of a FRET Probe Designed for Crowding Studies.
AB  - Living cells are crowded with macromolecules and organelles. As a result, there
      is an urgent need for molecular sensors for quantitative, site-specific
      assessment of the macromolecular crowding effects on a myriad of biochemical
      processes toward quantitative cell biology and biophysics. Here we investigate
      the excited-state dynamics and translational diffusion of a novel FRET sensor
      (mCerulean-linker-mCitrine) in a buffer (PBS, pH 7.4) at room temperature.
      Complementary experiments were carried out on free CFP, YFP, and the cleaved FRET
      probe as controls. The wavelength-dependent fluorescence lifetime measurements of
      the donor and acceptor in the FRET probe, using the time-correlated single-photon
      counting technique, indicate an energy transfer efficiency of 6.8 +/- 0.9% in
      PBS, with distinct excited-state dynamics from the recombinant CFP and YFP. The
      estimated mCerulean-mCitrine distance in this FRET probe is 7.7 +/- 0.2 nm. The
      energy transfer efficiency increases (11.5 +/- 0.9%) as the concentration of
      Ficoll-70 increases over the range of 0-300 g/L with an estimated mCerulean
      mCitrine distance of 6.1 +/- 0.2 nm. Complementary time-resolved anisotropy
      measurements suggest that the rotational diffusion of hetero-FRET in PBS is
      sensitive to the energy transfer from the donor to the acceptor. The results also
      suggest that the linker, -(GSG)6A(EAAAK)6A(GSG)6A(EAAAK)6A(GSG)6-, is rather
      flexible, and the observed rotational dynamics is likely to be due to a segmental
      mobility of the FRET pairs rather than an overall tumbling motion of a rigid
      probe. Comparative studies on a new construct of a FRET probe with a shorter,
      more flexible linker, mCerulean-(GSG)18-mCitrine, reveal enhanced energy transfer
      efficiency. On the millisecond time scale, fluorescence fluctuation analyses of
      the acceptor (excited at 488 nm) provide a means to examine the translational
      diffusion coefficient of the FRET probe. The results also suggest that the linker
      is flexible in this FRET probe, and the observed diffusion coefficient is faster
      than predicted as compared to the cleaved FRET probe. Our results serve as a
      point of reference for this FRET probe in a buffer toward its full potential as a
      sensor for macromolecular crowding in living cells and tissues.

PMID- 28520432
TI  - Insights into Glycol Ether-Alkanol Mixtures from a Combined Experimental and
      Theoretical Approach.
AB  - The binary liquid mixtures of glycol ethers (glymes) + 1-alkanol were
      characterized from the microscopic and macroscopic viewpoints through a combined
      experimental and theoretical study. Structuring, dynamics, and intermolecular
      forces were determined using density functional theory and classical molecular
      dynamics methods. The macroscopic behavior was studied though the measurement of
      relevant physicochemical properties and Raman IR studies. The changes in
      intermolecular forces with mixture composition, temperature, and the effects from
      the types of glymes as well as 1-alkanols were considered. Hydrogen bonding in
      the mixed fluids, its changes upon mixing, and mixture composition showed a large
      effect on fluids' structure and determined most of the fluids' properties
      together with the presence of hydrophobic domains from long 1-alkanols.

PMID- 28520433
TI  - Toward a Rigorous Definition of a Strength of Any Interaction Between Bader's
      Atomic Basins.
AB  - Strength of interaction between Bader's atomic basins, enclosed by zero-flux
      surfaces of electron distribution, was proposed to be a measure of elastic
      deformation of an interaction. The set containing 53 atomic aggregate and
      covering all range of interaction strength (from van der Waals interactions to
      triple covalent bonds) was calculated by DFT and perturbation theory methods.
      Further analysis was performed to seek correlations between various local
      quantities based on electron density and effective force constants of stretching
      diatomic vibrations. The linear trend between effective force constants and the
      potential energy density at the (3, -1) critical point of electron distribution
      was found. This correlation was improved by the integration of the potential
      energy density over an interbasin zero-flux surface of electron density. Simple
      mechanical explanation of established trends is presented. The correlations can
      be further used to at least semiquantitatively compare any pair of interactions
      between Bader's atomic basins.

PMID- 28520434
TI  - The Nature of Electron Mobility in Hybrid Perovskite CH3NH3PbI3.
AB  - CH3NH3PbI3 is one of the most promising candidates for cheap and high-efficiency
      solar cells. One of its unique features is the long carrier diffusion length
      (>100 MUm), but its carrier mobility is rather modest. The nature of the mobility
      is unclear. Here, using nonadiabatic wave function dynamics simulations, we show
      that the random rotations of the CH3NH3 cations play an important role in the
      carrier mobility. Our previous work showed that the electron and hole wave
      functions were localized and spatially separated due to the random orientations
      of the CH3NH3 cations in the tetragonal phase. We find that the localized
      carriers are able to conduct random walks due to the electrostatic potential
      fluctuation caused by the CH3NH3 random rotations. The calculated electron
      mobilities are in the experimentally measured range. We thus conclude that the
      carrier mobility of CH3NH3PbI3 is likely driven by the dynamic disorder that
      causes the fluctuation of the electrostatic potential.

PMID- 28520435
TI  - Modulation of Electron-Phonon Coupling in One-Dimensionally Nanorippled Graphene
      on a Macrofacet of 6H-SiC.
AB  - Local electron-phonon coupling of a one-dimensionally nanorippled graphene is
      studied on a SiC(0001) vicinal substrate. We have characterized local atomic and
      electronic structures of a periodically nanorippled graphene (3.4 nm period)
      prepared on a macrofacet of the 6H-SiC crystal using scanning tunneling
      microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy
      (ARPES). The rippled graphene on the macrofacets distributes homogeneously over
      the 6H-SiC substrate in a millimeter scale, and thus replica bands are detected
      by the macroscopic ARPES. The STM/STS results indicate the strength of electron
      phonon coupling to the out-of-plane phonon at the K points of graphene is
      periodically modified in accordance with the ripple structure. We propose an
      interface carbon nanostructure with graphene nanoribbons between the surface
      rippled graphene and the substrate SiC that periodically modifies the electron
      phonon coupling in the surface graphene.

PMID- 28520436
TI  - Controlling Structure and Function of Polymeric Drug Delivery Nanoparticles Using
      Microfluidics.
AB  - We demonstrate control of multiscale structure and drug delivery function for
      paclitaxel (PAX)-loaded polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO)
      polymeric nanoparticles (PNPs) via synthesis and flow-directed shear processing
      in a two-phase gas-liquid microfluidic reactor. This strategy takes a page from
      the engineering of commodity plastics, where processing rather than polymer
      chemistry provides an experimental handle on properties and function. PNPs formed
      from copolymers with three different PCL block lengths show sizes, morphologies,
      and loading efficiencies that depend on both the PCL block length and the
      microfluidic flow rate. By varying flow rate and comparing with a conventional
      bulk method of PNP preparation, we show that flow-variable shear processing
      provides control of PNP sizes and morphologies and enables slower PAX release
      times (up to 2 weeks) compared to bulk-prepared PNPs. Antiproliferative effects
      against cultured MCF-7 breast cancer cells were greatest for PNPs formed at an
      intermediate flow rate, corresponding to small and low-polydispersity spheres
      formed uniquely at this flow condition. Formation and flow-directed nanoscale
      shear processing in gas-liquid microfluidic reactors provides a manufacturing
      platform for drug delivery PNPs that could enable more effective and selective
      nanomedicines through multiscale structural control.

PMID- 28520437
TI  - Synthesis of Fused Polycyclic 1,4-Benzodiazepines via Metal-Free Cascade [5 +
      2]/[2 + 2] Cycloadditions.
AB  - A metal-catalyst-free, mild, and efficient synthetic protocol for polycyclic 1,4
      benzodiazepines via cascade [5 + 2]/[2 + 2] cycloadditions between pyridinium
      zwitterions and arynes is reported. Mechanistic experiments revealed that
      pyridinium zwitterions act as 1,5-dipoles in [5 + 2] cycloadditions with arynes
      for the construction of 1,4-benzodiazepines, which further undergo [2 + 2]
      cycloaddition resulting in the one-pot formation of one C-N bond and three C-C
      bonds.

PMID- 28520438
TI  - Noncovalent Surface Modification of Cellulose Nanopapers by Adsorption of
      Polymers from Aprotic Solvents.
AB  - Basic adsorption of hydrophobic polymers from aprotic solvents was introduced as
      a platform technology to modify exclusively the surfaces of cellulose nanopapers.
      Dynamic vapor sorption demonstrated that the water vapor uptake ability of the
      nanopapers remained unperturbed, despite strong repellency to liquid water caused
      by the adsorbed hydrophobic polymer on the surface. This was enabled by the fact
      that the aprotic solvents used for adsorption did not swell the nanopaper unlike
      water that is generally applied as the adsorption medium in such systems. As case
      examples, the adsorptions of polystyrene (PS) and poly(trifluoroethylene) (PF3E)
      were followed by X-ray photoelectron spectroscopy and water contact angle
      measurements, backed up with morphological analysis by atomic force microscopy.
      The resulting nanopapers are useful in applications like moisture buffers where
      repellence to liquid water and ability for moisture sorption are desired
      qualities.

PMID- 28520439
TI  - Cobalt(III)-Catalyzed Oxadiazole-Directed C-H Activation for the Synthesis of 1
      Aminoisoquinolines.
AB  - Aromatic heterocycles have been identified as effective directing groups (DGs) in
      C-H functionalization but can be retained as undesired bulky substituents in the
      final products. Herein, we report a Co(III)-catalyzed 1-aminoisoquinoline
      synthesis strategy based on oxadiazole-directed aromatic C-H coupling with
      alkynes and a subsequent redox-neutral C-N cyclization reaction. This labile N-O
      bond-based protocol has allowed the toleration of a broad range of functional
      groups.

PMID- 28520440
TI  - Synthesis of 3-Benzo[b]thienyl 3-Thienyl Ether via an Addition-Elimination
      Reaction and Its Transformation to an Oxygen-Fused Dithiophene Skeleton:
      Synthesis and Properties of Benzodithienofuran and Its pi-Extended Derivatives.
AB  - The synthesis of 3-benzo[b]thienyl 3-thienyl ether and its dehydrogenative
      cyclization leading to benzodithienofuran (BDTF; [1]benzothieno[3,2-b]thieno[2,3
      d]furan) are described for the first time. Further transformation of BDTF to more
      pi-extended BDTF derivatives and their fundamental physical properties are also
      studied.

PMID- 28520441
TI  - Total Syntheses of Arcyriaflavin A and Calothrixin B Using 2,2'-Bisindole-3
      acetic Acid Derivative as a Common Intermediate.
AB  - A new protocol for the synthesis of 2,2'-bisindole-3-acetic acid derivatives from
      aldimines derived from 2-aminocinnamic acid derivatives and indole-2
      carboxaldehyde was developed via a cyanide-catalyzed imino-Stetter reaction. With
      this protocol, the divergent total syntheses of arcyriaflavin A, a representative
      indolocarbazole natural product, and calothrixin B, a representative indolo[3,2
      j]phenanthridine natural product, were completed using a 2,2'-bisindole-3-acetic
      acid derivative as the common intermediate.

PMID- 28520442
TI  - T-2 Toxin-3alpha-glucoside in Broiler Chickens: Toxicokinetics, Absolute Oral
      Bioavailability, and in Vivo Hydrolysis.
AB  - Due to the lack of information on bioavailability and toxicity of modified
      mycotoxins, current risk assessment on these modified forms assumes an identical
      toxicity of the modified form to their respective unmodified counterparts.
      Crossover animal trials were performed with intravenous and oral administration
      of T-2 toxin (T-2) and T-2 toxin-3alpha-glucoside (T2-G) to broiler chickens.
      Plasma concentrations of T2-G, T-2, and main phase I metabolites were quantified
      using a validated liquid chromatography-tandem mass spectrometry method with a
      limit of quantitation for all compounds of 0.1 ng/mL. Resulting plasma
      concentration-time profiles were processed via two-compartmental toxicokinetic
      models. No T-2 triol and only traces of HT-2 were detected in the plasma samples
      after both intravenous and oral administration. The results indicate that T-2 has
      a low absolute oral bioavailability of 2.17 +/- 1.80%. For T2-G, an absorbed
      fraction of the dose and absolute oral bioavailability of 10.4 +/- 8.7% and 10.1
      +/- 8.5% were observed, respectively. This slight difference is caused by a
      minimal (and neglectable) presystemic hydrolysis of T2-G to T-2, that is, 3.49 +/
      1.19%. Although low, the absorbed fraction of T2-G is 5 times higher than that
      of T-2. These differences in toxicokinetics parameters between T-2 and T2-G
      clearly indicate the flaw in assuming equal bioavailability and/or toxicity of
      modified and free mycotoxins in current risk assessments.

PMID- 28520444
TI  - Enhancing Singlet Fission Dynamics by Suppressing Destructive Interference
      between Charge-Transfer Pathways.
AB  - We apply a real-time path-integral approach to investigate the charge-transfer
      (CT)-mediated singlet fission quantum dynamics in a model pentacene dimer. Our
      path-integral method gives reliable fission dynamics across various reaction
      regimes as well as a broad range of reorganization energies and temperatures.
      With this method, we investigated the destructive interference between the two CT
      mediated fission pathways and discovered two mechanisms that can suppress this
      deleterious effect. First, increasing the energy gap between the two CT states
      effectively shuts down the high-lying CT pathway, leaving a better functioning
      low-lying CT pathway with a minimum amount of destructive interference. Second,
      intermolecular vibrations induce electronic coupling fluctuations, such that the
      destructive cancellations due to the different signs in static electronic
      couplings are suppressed. Our numerical results suggest that these two effects
      can enhance the fission rate up to three times. These findings reveal promising
      design principles for more efficient singlet fission materials.

PMID- 28520443
TI  - Effective Interactions and Colloidal Stability of Bovine gamma-Globulin in
      Solution.
AB  - Interactions and phase behavior of gamma-globulins are of fundamental interest in
      biophysical and pharmaceutical research, as these are among the most abundant
      proteins in blood plasma. In this work, we report the characterization of the
      oligomeric state of bovine gamma-globulin, the effective protein-protein
      interactions, and the colloidal stability in aqueous solution as a function of
      protein concentration and ionic strength. Classical biochemical techniques, such
      as size exclusion chromatography (SEC) and gel electrophoresis, together with
      small-angle X-ray and neutron scattering (SAXS/SANS), were employed for this
      study. The results show that bovine gamma-globulin solutions are dominated by
      monomer and idiotype anti-idiotype dimer. Despite the flexibility and highly
      nonspherical shape of the protein, a simple model with a disk-type form factor
      and a structure factor of a square-well potential provide a satisfying
      description of the scattering data. The overall interactions are attractive and
      the strength decreases with increasing protein concentration, or adding buffer or
      salts. For higher protein volume fraction (>7%), the model would imply a strong
      particle-particle correlation which does not appear in the experimental data.
      This mismatch is most likely due to the smearing effect of the conformation
      change of proteins in solution. The stability of gamma-globulin solutions is
      highly sensitive to protein concentration, ionic strength, and the type of added
      salts, such as NaCl, Na2SO4, and NaSCN. For solutions below 50 mg/mL and at low
      ionic strengths (<0.1 M), protein aggregation is most likely due to
      subpopulations of IgG molecules with attractive patches of complementary surface
      charge. This effect is reduced for higher protein concentration due to self
      buffering effects. For high ionic strength (>1 M), typical salting-in (with
      NaSCN) and salting-out effects (with NaCl and Na2SO4) are observed. Results are
      further discussed in comparison with current studies in the literature on
      monoclonal antibodies.

PMID- 28520445
TI  - Telodendrimers for Physical Encapsulation and Covalent Linking of Individual or
      Combined Therapeutics.
AB  - New therapeutics for glioblastoma multiforme and our ability to deliver them
      using efficient nanocarriers constitute topical areas of research. We report a
      comparative study of temozolomide and quercetin in the treatment of glioblastoma
      (GBM) in three-dimensions, and their incorporation into micelles obtained from
      synthetically articulated architectural copolymers, and a commercially available
      linear polymer poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA). A
      versatile synthetic methodology to telodendrimers, which can be easily adapted to
      the needs of other therapeutic interventions, is presented. These dendritic block
      copolymers self-assemble into micelles and offer a platform for single or
      combination drug therapy. Telodendrimer micelles loaded with quercetin did not
      exhibit superior cell killing effect over the free drug, but acetazolamide, an
      inhibitor carbonic anhydrase IX, significantly reduced GBM cell viability in 3D
      spheroids. Results from these studies show that high loading of drugs into
      telodendrimer micelles requires a physical fit between the biologically active
      agent and telodendrimer nanocarrier, and points toward new possibilities for
      incorporation of chemotherapeutic and other agents to enhance their
      effectiveness.

PMID- 28520447
TI  - [Controversies around QALYs].
AB  - The paper summarizes the criticisms of the QALY concept utilization in health
      economic evaluations that has been growing stronger in the last years. Despite of
      its limitations, the QALY concept has been routinely used in many countries incl.
      the Czech Republic. However, some states disapproved QALYs as an optimizing
      criterion at the level of their political decisions. The critical reflection
      concerns both the theoretical and the experimental issues. Based on a literary
      review, fundamental arguments against the concept are summarized, and a synthesis
      of material objections is presented. The critical arguments focus on the
      foundations of the QALY concept in the economic theory, some ethical principles,
      inconsistencies and technical imperfections of the quality-of-life measurement
      tools used in QALY calculations, the substitution rule, differences between
      various diagnoses, and disregarding some other important parameters. As a whole,
      the critics' arguments can be judged as quite strong. The future will show
      whether the critical arguments summarized in this paper will lead to a
      development of alternative tools that have a potential of eliminating
      imperfections in QALYs, and consequently provide more complex data for the
      decision process.Key words: cost-effectiveness - health technology assessment -
      HTA - QALY - utility measure for medical interventions.

PMID- 28520446
TI  - [Diabetic foot syndrome: importance of calf muscles MR spectroscopy in the
      assessment of limb ischemia and effect of revascularization].
AB  - AIM: The standard method for assessment of effect of revascularization in
      patients with diabetic foot (DF) and critical limb ischemia (CLI) is
      transcutaneous oxygen pressure (TcPO2). Phosphorus magnetic resonance
      spectroscopy (31P MRS) enables to evaluate oxidative muscle metabolism that could
      be impaired in patients with diabetes and its complications. The aim of our study
      was to compare MRS of calf muscle between patients with DF and CLI and healthy
      controls and to evaluate the contribution of MRS in the assessment of the effect
      of revascularization. METHODS: Thirty-four diabetic patients with DF and CLI
      treated either by autologous cell therapy (ACT; 15 patients) or percutaneous
      transluminal angioplasty (PTA; 12 patients) in our foot clinic during 2013-2016
      and 19 healthy controls were included into the study. TcPO2 measurement was used
      as a standard method of non-invasive evaluation of limb ischemia. MRS
      examinations were performed using the whole-body 3T MR system 1 day before and 3
      months after the procedure. Subjects were examined in a supine position with the
      coil fixed under the m. gastrocnemius. MRS parameters were obtained at rest and
      during the exercise period. Rest MRS parameters of oxidative muscle metabolism
      such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE),
      adenosine triphosphate (ATP), dynamic MRS parameters such as recovery constant
      PCr (tauPCr) and mitochondrial capacity (Qmax), and pH were compared between
      patients and healthy controls, and also before and 3 months after
      revascularization. RESULTS: Patients with CLI had significantly lower PCr/Pi (p <
      0.001), significantly higher Pi and pH (both p < 0.01), significantly lower Qmax
      and prolonged tauPCr (both p < 0.001) in comparison with healthy controls. We
      observed a significant improvement in TcPO2 at 3 months after revascularization
      (from 26.4 +/- 11.7 to 39.7 +/- 17.7 mm Hg, p < 0.005). However, the rest MRS
      parameters did not change significantly after revascularization. In individual
      cases we observed improvement of dynamic MRS parameters. There was no correlation
      between MRS parameters and TcPO2 values. CONCLUSION: Results of our study show
      impaired oxidative metabolism of calf muscles in patients with CLI in comparison
      with healthy controls. We observed an improvement in dynamic MRS parameters in
      individual cases; this finding should be verified in a large number of patients
      during longer follow-up.Key words: autologous cell therapy - critical limb
      ischemia - diabetic foot - MR spectroscopy.

PMID- 28520448
TI  - [The role of cardiovascular magnetic resonance imaging in the diagnosis of
      hypertrophic cardiomyopathy. Part II].
AB  - Hypertrophic cardiomyopathy is currently understood as a group of diseases with
      left ventricular hypertrophy, which are not based on adaptive mechanisms. The
      first part of the review details the possibility of cardiac magnetic resonance in
      the diagnosis of sarcomeric forms of hypertrophic cardiomyopathy, the second part
      will focus on the possibilities of distinguishing the sarcomeric forms from their
      phenocopies.Key words: cardiac magnetic resonance - hypertrophic cardiomyopathy -
      phenocopies.

PMID- 28520449
TI  - [Novelties in the treatment of heart failure].
AB  - Heart failure (HF) is a complex clinical syndrome which is manifested by
      characteristic symptoms and objective signs of cardiac insufficiency. The
      incidence of HF, particularly its chronic form, is estimated 0.4-2 % in the
      central and western Europe, with an increase in higher age groups, affecting 10
      20 % of the population aged over 80. With respect to its growing incidence and
      prevalence, novel modalities of pharmacological and non-pharmacological treatment
      are being developed in order to improve quality of life and survival of the
      affected patients. This review based on up-to-date guidelines focuses in the
      first part on brief description of the possibilities of diagnosing heart failure,
      including the novelties arising out from the latest clinical and preclinical
      studies (such as soluble ST2, FSTL1, etc), further it concentrates on innovations
      in pharmacological treatment of chronic (ivabradine, ARNI, gliflozins) and acute
      (ularitide, serelaxin, nesiritide) HF. The last part provides an overview of
      available non-pharmacological HF therapeutics options (modulation of cardiac
      contraction, influencing the activity of sympathetic and parasympathetic nervous
      systems and permanent and temporary device support).Key words: ARNI - ECMO -
      gliflozins - heart failure - modulation of sympathetic and parasympathetic
      nervous systems - sacubitril-valsartan - therapy.

PMID- 28520450
TI  - [AT1 blockers - comparability with ACE inhibitors].
AB  - The reduction in overall mortality, cardiovascular mortality and the occurrence
      of myocardial infarction in patients treated with AT1 blockers is comparable with
      the use of ACE inhibitors. In addition, there is a lower proportion of AT1
      blockers withdrawal of treatment due to adverse reactions.Key words: ACE
      inhibitors - AT1 blockers - cardioprotection - hypertension - renin-angiotensin
      aldosteron system.

PMID- 28520451
TI  - [How to create cooperative patient for antihypertensive and hypolipidemic
      therapy].
AB  - Patient drug adherence is a major problem especially in the prevention of
      cardiovascular disease of atherosclerotic origin. On one hand, antihypertensive
      drugs and hypolipidemic drugs/statins are among the most successful, ones the
      other hand, they are among the drugs which are most frequently skipped by the
      patients. Improvement could be realized by education of patients, more frequent
      follow-ups, as well as by the use of new technologies involving specific
      dispensers and other, even more sophisticated methods. Nevertheless, among the
      most successful strategies is the simplification of medication, particularly the
      use of drugs with a longer half-life and the use of combination of several drugs
      in a single tablet. Therefore, we have quite wide range of options to improve
      patient compliance. However, some disadvantages should be kept in mind associated
      with these techniques. The aim of this article is to discuss potential problems
      and solutions associated with patient adherence/compliance with respect to
      antihypertensive and hypolipidemic treatment with an emphasis on practical
      approach.Key words: drug adherence - dyslipidemia - hypertension -
      pharmacotherapy.

PMID- 28520453
TI  - [Indeterminate cell histiocytosis - disappearance of skin infiltration following
      electron beam therapy and an application of 2-chlorodeoxyadenosine: case report].
AB  - Indeterminate cell histiocytosis is a rare disease belonging to the group of
      malignant histiocytic diseases. The disease predominantly affects the skin. The
      disease appeared in the described patient at the age of 80 years. Morphs began to
      develop on the skin and rapidly spread over the whole body including the face.
      Only the hands and feet were left uncovered. The patients skin samples were taken
      from 2 sites for histological examination. The resulting conclusion was
      indeterminate cell histiocytosis. The treatment we chose was analogous to the
      procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the
      first-line treatment. This treatment is frequently efficient for skin forms of
      Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy
      did not influence the disease activity at all. As the second-line treatment, we
      used low-energy electron beam irradiation in the total dose of 36.2 Gy. This
      treatment had a positive impact, morphs began to diminish and slowly disappear
      from the skin. But they have not disappeared completely, therefore we assessed
      the treatment effect of the radiotherapy itself as partial remission of the
      disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a
      dose of 5 mg/m2/per day, administered via subcutaneous injection over 5
      consecutive days in monthly intervals. There were three cycles of this treatment
      administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated
      without any adverse effects. The patient aged 82 years was only administered 3
      cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from
      any pathological morphs and only some pigmentation spots remained, we finished
      the treatment. The skin expressions of indeterminate cell histiocytosis
      completely disappeared after electron beam irradiation and the following
      administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short,
      however, after 6 months the disease recurred and the treatment is planned to
      resume. We assume the disease regresses following administration of 2
      chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to
      reach a longer-term response.Key words: electron beam irradiation - indeterminate
      cell histiocytosis - 2-chlorodeoxyadenosine.

PMID- 28520452
TI  - [Relapsing autoimmune pancreatitis type 1: case report].
AB  - Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, classified
      into 2 subtypes - AIP type 1 and AIP type 2. We present a case of a 31-years-old
      female admitted to our institution with upper abdominal pain and obstructive
      jaundice. Endoscopic retrograde cholangiopancreatoscopy (ERCP) revealed stenosis
      of intrapancreatic distal bile duct. Diffuse parenchymal enlargement and typical
      features of AIP were shown by computed tomography (CT) and endoscopic
      ultrasonography (EUS). The patient's serum IgG4 was elevated at 3.8 g/l (range
      0.08-1.4 g/l). She was diagnosed with AIP type 1 and treated with prednisone
      (initial dose of 30 mg per day, then tapered by 5 mg/day every week). The
      maintenance dose of 5 mg per day was continued for 6 months. Despite clinical and
      radiological remission, serum levels of IgG4 remained elevated. The patient
      experienced disease relapse 25 months after first attack. Moreover, new finding
      of calcifications occured in pancreas. The relapse was managed with
      corticosteroids and maintenance immunosupression with azathioprin was started.
      Literature review on risk factor of relapse, long-term immunosupressive therapy
      indication and optimal follow-up of AIP type 1 patients are discussed.Key words:
      autoimmune pancreatitis type 1 - long-term follow-up - relapse - therapy.

PMID- 28520454
TI  - Acupuncture "Rewires" the Brain ... with Lasting Effects.

PMID- 28520455
TI  - Quantitative determination of AVI-7100 (Radavirsen), a phosphorodiamidate
      morpholino oligomer (PMOplus(r) ), in human plasma using LC-MS/MS.
AB  - AIM: AVI-7100 (Radavirsen) is a 20-mer phosphorodiamidate morpholino oligomer
      (PMOplus(r)) for the treatment of influenza. Results/methodology: An automated
      solid-phase extraction method was used to extract plasma samples (200 MUl). The
      extracts were analyzed using liquid chromatography coupled with tandem mass
      spectrometry under the positive ionization mode. This method was fully validated
      over the calibration curve range of 5.00-1000 ng/ml. The between-run precision
      and accuracy ranged from 0.0 to 5.2% relative standard deviation and 91.6 to
      100.0% of nominal for all quality control concentrations, including the lower
      limit of quantitation. DISCUSSION/CONCLUSION: This is the first liquid
      chromatography coupled with tandem mass spectrometry method for the measurement
      of AVI-7100 concentrations in human plasma. It has been used to support regulated
      bioanalysis.

PMID- 28520457
TI  - Measuring and using free drug concentrations: has there been 'real' progress?

PMID- 28520456
TI  - Development and validation of a micellar liquid chromatographic method to
      determine three antitumorals in plasma.
AB  - AIM: A micellar liquid chromatographic method to determine several anticancer
      drugs (pazopanib, dabrafenib and regorafenib) in plasma was developed and
      validated by the guidelines of the EMA. EXPERIMENTAL: Plasma samples were
      directly injected, after a 1/5-dilution in a micellar solution. The drugs were
      resolved in <18 min using a C18 column. The mobile phase was an aqueous solution
      of 0.12 M SDS - 2% 1-pentanol, buffered at pH 7. The detection was performed by
      absorbance at 260 nm. RESULTS: The values of the main validation parameters were:
      LOD (0.1-1 mg/l), calibration range (0.2-2 to 80 mg/l), accuracy (-12.5 to
      +11.7%) and precision (<11.9%). CONCLUSION: The procedure was conducted by
      minimum cost, effort, manipulation, time and quantity of hazardous chemicals. The
      method was useful to determine the drugs at their respective target
      concentrations, and was found useful for clinical analysis.

PMID- 28520458
TI  - Anchored Transosseous-Equivalent Versus Anchorless Transosseous Rotator Cuff
      Repair: A Biomechanical Analysis in a Cadaveric Model.
AB  - BACKGROUND: The original approach for the repair of torn rotator cuffs involved
      an open technique with sutures passing through the greater tuberosity and tendon.
      The development of suture anchors allowed for an all-arthroscopic approach with
      anchor configurations attempting to re-create a transosseous fixation pattern.
      Presently, an arthroscopic approach can be combined with a transosseous suture
      configuration without using anchors. PURPOSE: To evaluate cyclic loading,
      ultimate load to failure, and the failure mechanisms of transosseous-equivalent
      (TOE) repair with anchors and anchorless transosseous (AT) repair of rotator cuff
      tears. STUDY DESIGN: Controlled laboratory study. METHODS: Supraspinatus tears
      (25 mm) were created in 20 fresh-frozen, human cadaveric shoulders, which were
      randomized to TOE or AT repair (10 in each group, paired experimental design).
      Biomechanical testing was performed with an initial preload, cyclic loading, and
      load to failure. Optical markers were used to monitor gap formation in 3 planes,
      and the failure mode was recorded. Paired t tests were used to make comparisons
      of biomechanical parameters between the groups. Multinomial logistic regression
      was used to compare failure modes between the groups. Significance was set to
      .05. RESULTS: The TOE group had a significantly higher mean (+/-SD) ultimate
      failure load (578.5 +/- 123.8 N) than the AT group (468.7 +/- 150.9 N) ( P =
      .034). The TOE group also had a significantly less mean first-cycle excursion
      (2.97 +/- 1.97 mm) than the AT group (4.70 +/- 2.04 mm) ( P = .046). There were
      no significant differences between the groups in cyclic elongation or linear
      stiffness during cyclic loading. Primary modes of failure were a type 2 tendon
      tear with medial tendon disruption in the TOE group (7/10) and a type 1 tendon
      tear with lateral tendon disruption in the AT group (6/10). CONCLUSION: TOE
      repair resulted in a significantly higher mean failure load compared with AT
      repair in a cadaveric model. The most common modes of failure were a type 2
      tendon tear in the TOE group and a type 1 tendon tear in the AT group. CLINICAL
      RELEVANCE: A higher mean failure load in TOE versus AT constructs may come at the
      cost of a less favorable failure mode adjacent to medial anchors at the
      musculotendinous junction, potentially making revision difficult.

PMID- 28520459
TI  - Feedback from the EBF - Focus Workshop: bringing assay validation and analysis of
      biomarkers into practice.
AB  - European Bioanalysis Forum Focus Workshop, Lisbon, Portugal, 9-10 June 2016 At
      the recent European Bioanalysis Forum's Focus Workshop 'Bringing Assay Validation
      and Analysis of Biomarkers into Practice', the discussion on best practice for
      biomarker assay validation continued. Both the presentations and the adjacent
      panel discussions yielded valuable food for thought for the broader bioanalytical
      community. The present conference report summarizes the essence from these
      discussions and from the proposals or conclusions made by all delegates on how to
      increase the necessary connectivity of the stakeholders involved in the
      bioanalysis of biomarkers.

PMID- 28520460
TI  - The Influence of Body Mass Index on Outcomes After Hip Arthroscopic Surgery With
      Capsular Plication for the Treatment of Femoroacetabular Impingement.
AB  - BACKGROUND: It remains unknown how variations in body mass index (BMI) influence
      outcomes after primary hip arthroscopic surgery with capsular plication for
      femoroacetabular impingement (FAI). PURPOSE: To evaluate the effect that abnormal
      BMI (namely, overweight, obese, morbidly obese, and underweight) versus normal
      weight has on patient-reported clinical outcomes more than 2 years
      postoperatively from primary hip arthroscopic surgery with capsular plication by
      a single surgeon. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A
      clinical repository containing patients undergoing primary hip arthroscopic
      surgery for FAI between January 1, 2012, and January 1, 2014, with a minimum 2
      year follow-up was queried. Outcome measures included the Hip Outcome Score (HOS)
      Activities of Daily Living (ADL), HOS-Sports, modified Harris Hip Score (mHHS),
      visual analog scale (VAS) for pain; satisfaction, and Patient Acceptable
      Symptomatic State (PASS) for the HOS-ADL; scores were collected preoperatively
      and at 3 months, 1 year, and minimum 2 years postoperatively. Included patients
      were segregated by preoperative BMI into the following categories: underweight
      (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese
      (30.0-34.9 kg/m2), and morbidly obese (>=35.0 kg/m2). A multivariate logistic
      regression model controlling for patient demographics and disease severity was
      used to identify independent associations between BMI categories and outcomes. A
      Bonferroni adjustment lowered the threshold for significance to P < .01. RESULTS:
      There were 409 hips in 381 patients appropriate for study inclusion: 7
      underweight, 197 normal BMI, 130 overweight, 31 obese, and 16 morbidly obese. The
      mean age was 33.1 +/- 12.1 years, with 232 (61%) female patients. At 2 years
      postoperatively, significant differences in the trend among HOS-ADL, HOS-Sports,
      and mHHS scores were evident, with normal BMI patients, followed by underweight
      patients, demonstrating greater scores than their overweight, obese, and morbidly
      obese counterparts. Obese patients demonstrated lower satisfaction scores than
      normal BMI patients. Overweight, obese, and morbidly obese patients had lower
      improvements in VAS pain scores compared with normal BMI patients. Increasing BMI
      (not subdivided into the 5 BMI categories) was associated with a higher infection
      risk (mean BMI for infections: 32.3 +/- 9.8 kg/m2 vs mean BMI for noninfections:
      25.2 +/- 4.8 kg/m2; P = .0035). However, with multivariate analysis, no
      significant differences in patient clinical outcomes between the BMI categories
      met the threshold for significance. Among obese patients (BMI >=30.0 kg/m2), no
      specific risk factors were found to be significantly associated with decreases in
      the change in VAS, HOS-ADL, HOS-Sports, mHHS, satisfaction, or PASS for the HOS
      ADL scores. However, because of the small cohort sizes at the extremes of the BMI
      categories, this analysis may have been underpowered to identify a significant
      difference in underweight or morbidly obese patients. CONCLUSION: In the current
      cohort, there were multiple potential confounding variables, and while some
      clinical differences were observed initially (higher HOS-ADL, HOS-Sports, and
      mHHS scores for normal BMI patients than overweight and obese patients at 2 years
      postoperatively; lower satisfaction scores for obese patients than normal BMI
      patients; and lower improvement in VAS pain scores for overweight, obese, and
      morbidly obese patients when compared with normal BMI patients), after
      multivariate analysis, no associations were observed between BMI and clinical
      outcomes after hip arthroscopic surgery with capsular plication for FAI.

PMID- 28520461
TI  - Clinical Outcome After Arthroscopic Debridement and Microfracture for
      Osteochondritis Dissecans of the Capitellum.
AB  - BACKGROUND: Various surgical treatment techniques have been developed to treat
      capitellar osteochondritis dissecans; however, the optimal technique remains the
      subject of ongoing debate. PURPOSE: To evaluate clinical outcomes after
      arthroscopic debridement and microfracture for advanced capitellar
      osteochondritis dissecans. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Between 2008 and 2015, the authors followed 77 consecutive patients (81
      elbows) who underwent arthroscopic debridement and microfracture, and loose body
      removal if needed, for advanced capitellar osteochondritis dissecans. Seventy-one
      patients (75 elbows) with a minimum follow-up of 1 year were included. The mean
      age was 16 years (SD, +/-3.3 years; range, 11-26 years) and the mean follow-up
      length was 3.5 years (SD, +/-1.9 years; range, 1-8.2 years). Based on CT and/or
      MRI results, 71 lesions were classified as unstable and 4 as stable. Clinical
      elbow outcome (pain, function, and social-psychological effect) was assessed
      using the Oxford Elbow Score (OES) at final follow-up (OES range, 0-48). Range of
      motion and return to sports were recorded. Multivariable linear regression
      analysis was performed to determine predictors of postoperative OES. RESULTS:
      Intraoperatively, there were 3 grade 1 lesions, 2 grade 2 lesions, 10 grade 3
      lesions, 1 grade 4 lesion, and 59 grade 5 lesions. The mean postoperative OES was
      40.8 (SD, +/-8.0). An open capitellar physis was a predictor of better elbow
      outcome (5.8-point increase; P = .025), as well as loose body removal/grade 4-5
      lesions (6.9-point increase; P = .0020) and shorter duration of preoperative
      symptoms (1.4-point increase per year; P = .029). Flexion slightly improved from
      134 degrees  to 139 degrees  ( P < .001); extension deficit slightly improved
      from 8 degrees  to 3 degrees  ( P < .001). Pronation ( P = .47) and supination
      did not improve ( P = .065). Thirty-seven patients (55%) returned to their
      primary sport at the same level, and 5 patients (7%) returned to a lower level.
      Seventeen patients (25%) did not return to sport due to elbow-related symptoms,
      and 10 patients (13%) did not return due to non-elbow-related reasons. No
      complications were recorded. CONCLUSION: Arthroscopic debridement and
      microfracture for advanced capitellar osteochondritis dissecans provide good
      clinical results, especially in patients with open growth plate, loose body
      removal, and shorter duration of symptoms. However, only 62% of patients in this
      study returned to sports.

PMID- 28520462
TI  - Activity-based proteomics in bioanalysis: past, present and future.

PMID- 28520463
TI  - A Preclinical Assessment of Early Continuous Passive Motion and Treadmill
      Therapeutic Exercises for Generating Chondroprotective Effects After Anterior
      Cruciate Ligament Rupture.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injury is a well-known risk factor
      for the development of posttraumatic osteoarthritis (PTOA). However, whether
      using continuous passive motion (CPM) with or without additional treadmill
      exercise (TRE) in early ACL injury might provide chondroprotective effects and
      further decrease the risk of PTOA has yet to be determined. HYPOTHESIS: CPM may
      offer an enhanced chondroprotective effect, but TRE may attenuate that effect due
      to the mechanical stress on the joint and inflammatory cytokines in the joint.
      STUDY DESIGN: Controlled laboratory study. METHODS: Thirty adult New Zealand
      White male rabbits were randomly allocated to sedentary (SED), CPM, TRE, or
      CPM+TRE groups. Each rabbit underwent an ACL transection (ACLT) on the right
      knee, with the contralateral knee used as an internal control (sham). The 4 joint
      surfaces (ie, medial and lateral femoral condyles and tibial plateaus) were
      evaluated 4 weeks after surgery for gross appearance, histological
      characteristics, and quantitative osteoarthritis (OA) scores. RESULTS: Overall,
      at the end of testing, the CPM group experienced the best protective therapeutic
      effects in all compartments. In gross appearance, CPM resulted in normal
      articular surfaces, while the TRE and SED groups exhibited surface abrasion.
      Histological analysis showed significant differences in articular cartilage
      status. The CPM group had significantly better histological OA scores ( P < .01),
      corresponding to the smoothest cartilage surface and sound chondrocyte and
      collagen arrangement. This group also showed abundant glycosaminoglycan (GAG)
      content and a sound growth microenvironment, with significantly lower expression
      levels of the inflammatory cytokine tumor necrosis factor alpha and the apoptotic
      marker caspase 3. In contrast, the TRE and SED groups showed several features of
      damage: distinct graded cartilage abrasion; damaged collagen fibers,
      corresponding to noticeable collagen type X (osteoarthritic cartilage); reduced
      cartilage thickness; fewer cartilaginous cells; and the appearance of chondrocyte
      clusters. These groups also showed loss of GAG, corresponding to higher levels of
      inflammatory cytokines and apoptosis of articular chondrocytes. Furthermore, the
      CPM+TRE group displayed visible pathological changes in the superficial
      cartilage, indicating that early loading exercise may contribute to
      osteoarthritis. The sham treatment showed no difference in the changes in all
      compartments between groups. CONCLUSION: Immediate CPM therapy produces a
      superior in situ microenvironment for reducing the occurrence of PTOA after ACL
      injury without reconstruction in rabbits. CLINICAL RELEVANCE: These data suggest
      that immediate application of CPM therapy may be necessary to create a sound
      microenvironment in joints and possibly to decrease the risk of PTOA without or
      while awaiting ACL reconstruction. In contrast, both early active loading
      exercise and inactivity lead to the development of PTOA.

PMID- 28520464
TI  - Suvorexant for the Treatment of Insomnia in Adolescents.
AB  - OBJECTIVES: Suvorexant is the first dual orexin receptor antagonist for treating
      insomnia. This study aimed to evaluate the tolerability, efficacy, and safety of
      suvorexant on insomnia in adolescents. METHODS: Thirty patients (8 male and 22
      female; mean standard deviation age: 15.7 +/- 2.4 years; range: 10-20) with
      insomnia were administered suvorexant. Clinical background, persistence rate, the
      Clinical Global Impression (CGI), and the Athens Insomnia Scale (AIS) were
      compared between patients who continued and discontinued suvorexant treatment.
      RESULTS: Seventeen patients (56.7%) successfully continued taking suvorexant.
      Among the 13 patients who did not continue treatment, 5 patients were lost to
      follow-up. Of the remaining eight who did not continue treatment, four decided to
      discontinue of their own accord, two decided to discontinue due to lack of
      effectiveness, and two decided to discontinue due to adverse reaction, namely
      abnormal dreams. Among patients who completed the study, CGI significantly
      decreased from 3.6 +/- 0.8 to 3.1 +/- 0.9 (p = 0.014). The score of sleep quality
      in AIS was significantly higher among the patients who discontinued suvorexant
      than those who continued suvorexant (p = 0.02). CONCLUSION: Our results indicate
      that suvorexant could be considered a treatment option for adolescents.

PMID- 28520465
TI  - Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Past, Present, and
      Future.
AB  - The concept of Regenerative Medicine combined with Cell based Therapy and Tissue
      Engineering represents the fourth pillar of healthcare and provides a promising
      approach for the treatment of serious diseases. Recently, cell based therapies
      are focused on the use of mesenchymal stem/stromal cells (MSCs). Human MSCs, that
      represent a mesoderm derived population of progenitors, are easily expanded in
      culture. They are capable to differentiate into osteoblasts, chondrocytes, and
      adipocytes and exhibit the potential to repair or regenerate damaged tissues. The
      best characterized source of human MSCs to date is the bone marrow; recently,
      fetal sources, such as amniotic fluid, umbilical cord, amniotic membranes, or
      placenta, have also attracted increased attention. Thus, MSCs may represent a
      valuable tool for tissue repair and cell therapeutic applications. To this end,
      the main focus of this review is to summarize and evaluate the key
      characteristics, the sources, and the potential use of MSCs in therapeutic
      approaches and modalities.

PMID- 28520466
TI  - Development and validation of a highly sensitive gradient chiral separation of
      pramipexole in human plasma by LC-MS/MS.
AB  - AIM: Development of a high-sensitivity chiral LC-MS/MS method was required to
      evaluate a combination of pramipexole (S-PPX) and its enantiomer dexpramipexole
      (R-PPX) in a proposed clinical trial. The previously available methods suffered
      from low sensitivity for the (S)-enantiomer in the presence of the more abundant
      (R)-enantiomer. Based on the projected dosing regimen in the clinical trial, a
      5000-fold improvement in sensitivity was required for the (S)-enantiomer.
      METHODOLOGY: Spiked human plasma samples were extracted by liquid-liquid
      extraction using ethyl acetate and injected onto a CHIRALPAK ID column under pH
      gradient conditions. CONCLUSION: An improved analytical method was developed and
      validated with a final LLQ for (S)-PPX of 0.1 ng/ml in the presence of 2000 ng/ml
      of (R)-PPX.

PMID- 28520467
TI  - Challenges in metabolomics-based disease molecular classification: an analytical
      perspective.

PMID- 28520468
TI  - The Hierarchy of Brain Networks Is Related to Insulin Growth Factor-1 in a Large,
      Middle-Aged, Healthy Cohort: An Exploratory Magnetoencephalography Study.
AB  - Recently, a large study demonstrated that lower serum levels of insulin growth
      factor-1 (IGF-1) relate to brain atrophy and to a greater risk for developing
      Alzheimer's disease in a healthy elderly population. We set out to test if
      functional brain networks relate to IGF-1 levels in the middle aged. Hence, we
      studied the association between IGF-1 and magnetoencephalography-based functional
      network characteristics in a middle-aged population. The functional connections
      between brain areas were estimated for six frequency bands (delta, theta, alpha1,
      alpha2, beta, gamma) using the phase lag index. Subsequently, the topology of the
      frequency-specific functional networks was characterized using the minimum
      spanning tree. Our results showed that lower levels of serum IGF-1 relate to a
      globally less integrated functional network in the beta and theta band. The
      associations remained significant when correcting for gender and systemic effects
      of IGF-1 that might indirectly affect the brain. The value of this exploratory
      study is the demonstration that lower levels of IGF-1 are associated with brain
      network topology in the middle aged.

PMID- 28520469
TI  - Carotid versus coronary atherosclerosis burdens in acute compared with chronic
      symptomatic coronary artery disease.
AB  - Prediction of coronary events remains elusive. Carotid atherosclerosis may be a
      surrogate for coronary risk, as carotid and coronary diseases occur
      simultaneously - albeit at times with a weak association - depending on clinical
      presentation. We investigated carotid and coronary atherosclerosis in men with
      new-onset unstable coronary artery disease (CAD) presenting with acute ST-segment
      elevation myocardial infarction (STEMI) vs. long-standing severe chronic stable
      angina (CSA). Bilateral carotid artery and 3-vessel coronary artery
      atherosclerosis burdens were measured within 1 month, respectively, by 3D
      volumetric carotid magnetic resonance imaging and coronary angiography-derived
      modified CASS-50 score. Men with STEMI (n = 50) and long-standing CSA (n = 50),
      matched for age, were enrolled (58.6 +/- 8.8 years). All of them had carotid
      atherosclerosis. Atherosclerosis burden was greater in the carotid arteries of
      STEMI vs. CSA (wall volume: 196.2 +/- 44.4 vs. 169.2 +/- 38.0 mm3/4 mm, p =
      0.002), but greater in the coronary arteries of CSA vs. STEMI (modified CASS-50
      score: 3 vs. 1, p < 0.0001). Normalized wall index (NWI) of internal carotid was
      associated with modified CASS-50 score in STEMI (rho = 0.40, p = 0.022) and in
      CSA (rho = -0.39, p = 0.031). Carotid atherosclerosis was observed in all CAD
      patients, and atherosclerosis burden in carotid and in coronary arteries varied
      according to clinical presentation.

PMID- 28520471
TI  - ?

PMID- 28520473
TI  - A New Method and Mass-Spectrometric Instrument for Extraterrestrial Microbial
      Life Detection Using the Elemental Composition Analyses of Martian Regolith and
      Permafrost/Ice.
AB  - We propose a new technique for the detection of microorganisms by elemental
      composition analyses of a sample extracted from regolith, permafrost, and ice of
      extraterrestrial bodies. We also describe the design of the ABIMAS instrument,
      which consists of the onboard time-of-flight laser mass-reflectron (TOF LMR) and
      the sample preparation unit (SPU) for biomass extraction. This instrument was
      initially approved to fly on board the ExoMars 2020 lander mission. The
      instrument can be used to analyze the elemental composition of possible
      extraterrestrial microbial communities and compare it to that of terrestrial
      microorganisms. We have conducted numerous laboratory studies to confirm the
      possibility of biomass identification via the following biomarkers: P/S and Ca/K
      ratios, and C and N abundances. We underline that only the combination of these
      factors will allow one to discriminate microbial samples from geological ones.
      Our technique has been tested experimentally in numerous laboratory trials on
      cultures of microorganisms and polar permafrost samples as terrestrial analogues
      for martian polar soils. We discuss various methods of extracting microorganisms
      and sample preparation. The developed technique can be used to search for and
      identify microorganisms in different martian samples and in the subsurface of
      other planets, satellites, comets, and asteroids-in particular, Europa, Ganymede,
      and Enceladus. Key Words: Mass spectrometry-Life-detection instruments-Biomarkers
      Earth Mars-Biomass spectra. Astrobiology 17, 448-458.

PMID- 28520474
TI  - Survival of Deinococcus geothermalis in Biofilms under Desiccation and Simulated
      Space and Martian Conditions.
AB  - Biofilm formation represents a successful survival strategy for bacteria. In
      biofilms, cells are embedded in a matrix of extracellular polymeric substances
      (EPS). As they are often more stress-tolerant than single cells, biofilm cells
      might survive the conditions present in space and on Mars. To investigate this
      topic, the bacterium Deinococcus geothermalis was chosen as a model organism due
      to its tolerance toward desiccation and radiation. Biofilms cultivated on
      membranes and, for comparison, planktonically grown cells deposited on membranes
      were air-dried and exposed to individual stressors that included prolonged
      desiccation, extreme temperatures, vacuum, simulated martian atmosphere, and UV
      irradiation, and they were exposed to combinations of stressors that simulate
      space (desiccation + vacuum + UV) or martian (desiccation + Mars atmosphere + UV)
      conditions. The effect of sulfatic Mars regolith simulant on cell viability
      during stress was investigated separately. The EPS produced by the biofilm cells
      contained mainly polysaccharides and proteins. To detect viable but nonculturable
      (VBNC) cells, cultivation-independent viability indicators (membrane integrity,
      ATP, 16S rRNA) were determined in addition to colony counts. Desiccation for 2
      months resulted in a decrease of culturability with minor changes of membrane
      integrity in biofilm cells and major loss of membrane integrity in planktonic
      bacteria. Temperatures between -25 degrees C and +60 degrees C, vacuum, and Mars
      atmosphere affected neither culturability nor membrane integrity in both
      phenotypes. Monochromatic (254 nm; >=1 kJ m-2) and polychromatic (200-400 nm;
      >5.5 MJ m-2 for planktonic cells and >270 MJ m-2 for biofilms) UV irradiation
      significantly reduced the culturability of D. geothermalis but did not affect
      cultivation-independent viability markers, indicating the induction of a VBNC
      state in UV-irradiated cells. In conclusion, a substantial proportion of the D.
      geothermalis population remained viable under all stress conditions tested, and
      in most cases the biofilm form proved advantageous for surviving space and Mars
      like conditions. Key Words: Biofilms-Desiccation-UV radiation-Mars
      Lithopanspermia. Astrobiology 17, 431-447.

PMID- 28520472
TI  - A Study of the Microbial Spatial Heterogeneity of Bahamian Thrombolites Using
      Molecular, Biochemical, and Stable Isotope Analyses.
AB  - Thrombolites are buildups of carbonate that exhibit a clotted internal structure
      formed through the interactions of microbial mats and their environment. Despite
      recent advances, we are only beginning to understand the microbial and molecular
      processes associated with their formation. In this study, a spatial profile of
      the microbial and metabolic diversity of thrombolite-forming mats of Highborne
      Cay, The Bahamas, was generated by using 16S rRNA gene sequencing and predictive
      metagenomic analyses. These molecular-based approaches were complemented with
      microelectrode profiling and in situ stable isotope analysis to examine the
      dominant taxa and metabolic activities within the thrombolite-forming
      communities. Analyses revealed three distinctive zones within the thrombolite
      forming mats that exhibited stratified populations of bacteria and archaea.
      Predictive metagenomics also revealed vertical profiles of metabolic
      capabilities, such as photosynthesis and carboxylic and fatty acid synthesis
      within the mats that had not been previously observed. The carbonate precipitates
      within the thrombolite-forming mats exhibited isotopic geochemical signatures
      suggesting that the precipitation within the Bahamian thrombolites is
      photosynthetically induced. Together, this study provides the first look at the
      spatial organization of the microbial populations within Bahamian thrombolites
      and enables the distribution of microbes to be correlated with their activities
      within modern thrombolite systems. Key Words: Thrombolites-Microbial diversity
      Metagenome-Stable isotopes-Microbialites. Astrobiology 17, 413-430.

PMID- 28520475
TI  - Kombucha Multimicrobial Community under Simulated Spaceflight and Martian
      Conditions.
AB  - Kombucha microbial community (KMC) produces a cellulose-based biopolymer of
      industrial importance and a probiotic beverage. KMC-derived cellulose-based
      pellicle film is known as a highly adaptive microbial macrocolony-a stratified
      community of prokaryotes and eukaryotes. In the framework of the multipurpose
      international astrobiological project "BIOlogy and Mars Experiment (BIOMEX),"
      which aims to study the vitality of prokaryotic and eukaryotic organisms and the
      stability of selected biomarkers in low Earth orbit and in a Mars-like
      environment, a cellulose polymer structural integrity will be assessed as a
      biomarker and biotechnological nanomaterial. In a preflight assessment program
      for BIOMEX, the mineralized bacterial cellulose did not exhibit significant
      changes in the structure under all types of tests. KMC members that inhabit the
      cellulose-based pellicle exhibited a high survival rate; however, the survival
      capacity depended on a variety of stressors such as the vacuum of space, a Mars
      like atmosphere, UVC radiation, and temperature fluctuations. The critical
      limiting factor for microbial survival was high-dose UV irradiation. In the tests
      that simulated a 1-year mission of exposure outside the International Space
      Station, the core populations of bacteria and yeasts survived and provided
      protection against UV; however, the microbial density of the populations overall
      was reduced, which was revealed by implementation of culture-dependent and
      culture-independent methods. Reduction of microbial richness was also associated
      with a lower accumulation of chemical elements in the cellulose-based pellicle
      film, produced by microbiota that survived in the post-test experiments, as
      compared to untreated cultures that populated the film. Key Words: BIOlogy and
      Mars Experiment (BIOMEX)-Kombucha multimicrobial community-Biosignature-Biofilm
      Bacterial cellulose. Astrobiology 17, 459-469.

PMID- 28520476
TI  - Early Life Growth Predictors of Childhood Adiposity Trajectories and Future Risk
      for Obesity: Birth to Twenty Cohort.
AB  - BACKGROUND: There is growing evidence of variations in adiposity trajectories
      among individuals, but the influence of early life growth patterns on these
      trajectories is underresearched in low- and middle-income countries. Therefore,
      our aim was to examine the association between early life conditional weight gain
      and childhood adiposity trajectories. METHODS: We previously identified distinct
      adiposity trajectories (four for girls and three for boys) in black South African
      children (boys = 877; girls = 947). The association between the trajectories and
      early life growth patterns, and future obesity risk was assessed by multivariate
      linear and multinomial logistic and logistic regressions. Conditional weight gain
      independent of height was computed for infancy (0-2 years) and early childhood (2
      4 years). RESULTS: Conditional weight gain before 5 years of age was
      significantly associated with early onset of obesity or overweight (excess
      weight) BMI trajectories in both boys and girls. In girls, greater conditional
      weight gain in infancy was associated with increased relative risk of being in
      the early-onset obese to morbid obese trajectory, with relative risk ratios of
      2.03 (95% confidence interval: 1.17-3.52) compared to belonging to a BMI
      trajectory in the normal range. Boys and girls in the early-onset obesity or
      overweight BMI trajectories were more likely to be overweight or obese in early
      adulthood. CONCLUSIONS: Excessive weight gain in infancy and early childhood,
      independent of linear growth, predicts childhood and adolescent BMI trajectories
      toward obesity. These results underscore the importance of early life factors in
      the development of obesity and other NCDs in later life.

PMID- 28520478
TI  - Violence Against Women and Household Ownership of Radios, Computers, and Phones
      in 20 Countries.
AB  - OBJECTIVES: To examine the relationship between household ownership of
      information and communication technologies (ICTs) and justifications for wife
      beating. METHODS: Women aged 15 to 49 years in 20 countries were surveyed via
      UNICEF's Multiple Indicator Cluster Surveys between 2006 and 2014. Multivariate
      logistic regressions accounted for individual-, household-, and structural-level
      variables. RESULTS: Household ownership of any ICT (radio, computer, fixed phone,
      or mobile phone but not television) was associated with increased odds of women
      rejecting wife beating. The largest association was with computer ownership:
      women in homes with a computer were more likely to reject wife beating (adjusted
      odds ratio [AOR] = 1.81; 97.5% confidence interval [CI] = 1.69, 1.93). Number of
      ICTs was important: women in households with 1, 2, 3, 4, and 5 ICTs (vs 0) were
      more likely to reject wife-beating justifications (AOR = 1.10 [97.5% CI = 1.03,
      1.17]; AOR = 1.10 [97.5% CI = 1.03, 1.18]; AOR = 1.19 [97.5% CI = 1.11, 1.29];
      AOR = 1.71 [97.5% CI = 1.54, 1.88]; and AOR = 2.85 [97.5% CI = 2.48, 3.26];
      respectively). CONCLUSIONS: Independent of household wealth, country development,
      and other sociodemographic factors, the more ICTs in a household, the more likely
      that women will reject wife-beating justifications. Policymakers and program
      planners should consider potential implications of ICT access relating to
      intimate partner violence.

PMID- 28520477
TI  - Minimum Stocking Requirements for Retailers in the Special Supplemental Nutrition
      Program for Women, Infants, and Children: Disparities Across US States.
AB  - OBJECTIVES: To examine state variation in minimum stocking requirements for
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      authorized small food retailers. METHODS: We obtained minimum stocking
      requirements for 50 states and the District of Columbia in 2017 from WIC Web
      pages or e-mail from the state WIC agency. We developed a coding protocol to
      compare minimum quantities and varieties required for 12 food and beverage
      categories. We calculated the median, range, and interquartile range for each
      measure. RESULTS: Nearly all states set minimum varieties and quantities of
      fruits and vegetables, 100% juice, whole grain-rich foods, breakfast cereal,
      milk, cheese, eggs, legumes, and peanut butter. Fewer states set requirements for
      canned fish, yogurt, and tofu. Most measures had a large range in minimum
      requirements (e.g., $8-$100 of fruits and vegetables, 60-144 oz of breakfast
      cereal). CONCLUSIONS: WIC-participating retailers must adhere to very different
      minimum stocking requirements across states, which may result in disparities in
      food and beverage products available to WIC recipients. Public Health
      Implications. The results provide benchmarks that can inform new local, state,
      and federal program and policy efforts to increase healthy food availability in
      retail settings.

PMID- 28520479
TI  - Dissecting the Complexities of the Relationship Between Police Officer-Civilian
      Race/Ethnicity Dyads and Less-Than-Lethal Use of Force.
AB  - OBJECTIVES: To examine how sublethal use-of-force patterns vary across officer
      civilian race/ethnicity while accounting for officer-, civilian-, and situational
      level factors. METHODS: We extracted cross-sectional data from 5630 use-of-force
      reports from the Dallas Police Department in 2014 and 2015. We categorized each
      officer-civilian interaction into race/ethnicity dyads. We used multilevel, mixed
      logistic regression models to evaluate the relationship between race/ethnicity
      dyads and the types of use of force. RESULTS: Forty-eight percent of use-of-force
      interactions occurred between a White officer and a non-White civilian (White-non
      White). In bivariate models, the odds of hard-empty hand control and intermediate
      weapon use were significantly higher among White-Black dyads compared with White
      White dyads. The bivariate odds of intermediate weapon use were also
      significantly higher among Black-Black, Hispanic-White, Black-Hispanic, and
      Hispanic-Black dyads compared with White-White dyads. However, after we
      controlled for individual and situational factors, the relationship between
      race/ethnicity dyad and hard-empty hand control was no longer significant.
      CONCLUSIONS: Although we observed significant bivariate relationships between
      race/ethnicity dyads and use of force, these relationships largely dissipated
      after we controlled for other factors.

PMID- 28520481
TI  - On the Origins of the Electronic Cigarette: British American Tobacco's Project
      Ariel (1962-1967).
AB  - Electronic cigarettes are advertised as the latest technological gadget-the
      smoking equivalent of smart phones. I challenge this sense of novelty by tracing
      their history to the 1960s, when researchers at British American Tobacco first
      recognized that smokers' brains were dependent on nicotine. This discovery
      enabled British American Tobacco to develop a novel kind of smoking device under
      the codename "Ariel" between 1962 and 1967. Whereas filters were meant to
      eliminate specific harmful constituents of tobacco smoke, Project Ariel tried to
      reduce smoking to its alkaloid essence: nicotine. By heating instead of burning
      tobacco, the scientists working on Ariel managed to produce an aerosol smoking
      device that delivered nicotine with very little tar while retaining the look and
      feel of a cigarette. However, after receiving two patents for Ariel, British
      American Tobacco ultimately decided to abandon the project to avoid endangering
      cigarettes, its main product. Today, as e-cigarettes are surging in popularity,
      it is worth revisiting Ariel because it is not just an episode in the history of
      aerosol smoking devices but its starting point.

PMID- 28520482
TI  - Foodborne Disease Outbreaks in Correctional Institutions-United States, 1998
      2014.
AB  - OBJECTIVES: To present the first update on the epidemiology of US foodborne
      correctional institution outbreaks in 20 years. METHODS: We analyzed data from
      the Centers for Disease Control and Prevention's Foodborne Disease Outbreak
      Surveillance System to describe correctional institution outbreaks from 1998 to
      2014 and compare them with other foodborne outbreaks. RESULTS: Two hundred
      foodborne outbreaks in correctional institutions were reported, resulting in 20
      625 illnesses, 204 hospitalizations, and 5 deaths. Median number of outbreak
      associated illnesses per 100 000 population per year was 45 (range = 11-141)
      compared with 7 (range = 4-10) for other outbreaks. These outbreaks accounted for
      6% (20 625 of 358 330) of outbreak-associated foodborne illnesses. Thirty-seven
      states reported at least 1 outbreak in a correctional institution. Clostridium
      perfringens (28%; 36 of 128) was the most frequently reported single etiology.
      The most frequently reported contributing factor was food remaining at room
      temperature (37%; 28 of 76). CONCLUSIONS: Incarcerated persons suffer a
      disproportionate number of outbreak-associated foodborne illnesses. Better food
      safety oversight and regulation in correctional food services could decrease
      outbreaks. Public Health Implications. Public health officials, correctional
      officials, and food suppliers can work together for food safety. Clearer
      jurisdiction over regulation of correctional food services is needed.

PMID- 28520483
TI  - Effect of the Affordable Care Act on Disparities in Breastfeeding: The Case of
      Maine.
AB  - OBJECTIVES: To evaluate the Affordable Care Act (ACA) breastfeeding provision and
      test whether changes in coverage affected women differently according to health
      insurance status. METHODS: We used the All-Payer Claims Database from Maine (2012
      2014) to compare health insurance claims for lactation classes and breast pumps
      between women with private insurance and women with Medicaid (1) before the ACA
      breastfeeding provision, (2) after the provision came into effect, and (3) after
      health insurance expansion through the Marketplace. RESULTS: We found limited
      change in claims for lactation classes over the study period. By contrast, the
      number of claims for breast pumps among women with private insurance increased
      from 70 claims in the third quarter of 2012 to 629 claims 1 year later and 803
      claims in the third quarter of 2014. Women with Medicaid had only 11 claims for
      breast pumps over the entire study period. CONCLUSIONS: This 11-fold rise in
      claims for breast pumps by women with private insurance suggests that these women
      will likely increase breastfeeding initiation or duration; however, without
      additional support for women with Medicaid, disparities in breastfeeding may
      increase.

PMID- 28520485
TI  - Consumption of Carbonated Soft Drinks Among Young Adolescents Aged 12 to 15 Years
      in 53 Low- and Middle-Income Countries.
AB  - OBJECTIVES: To compare consumption of carbonated soft drinks among young
      adolescents in 53 low- and middle-income countries (LMICs). METHODS: We used 2009
      to 2013 Global School-based Student Health Survey data to assess 137 449 young
      adolescents aged 12 to 15 years with available data (via a standardized
      questionnaire) on frequency of carbonated soft drink consumption. RESULTS:
      Overall, young adolescents reported having consumed carbonated soft drinks 1.39
      times per day (95% confidence interval [CI] = 1.26, 1.51), and 54.3% of
      adolescents reported consuming a carbonated soft drink at least once per day.
      Frequency (times per day) varied greatly across countries, ranging from 0.52 (95%
      CI = 0.43, 0.60) in Kiribati to 2.39 (95% CI = 2.25, 2.53) in Suriname.
      CONCLUSIONS: Our data confirm that consumption of carbonated soft drinks is
      frequent among young adolescents in LMICs. Our findings highlight the need for
      interventions in these countries to reduce adolescents' carbonated soft drink
      consumption.

PMID- 28520486
TI  - Trends in School-Related Victimization of Lesbian, Gay, and Bisexual Youths
      Massachusetts, 1995-2015.
AB  - OBJECTIVES: To compare changes over time in prevalence of school victimization
      among lesbian, gay, and bisexual (LGB) students compared with heterosexual
      students. METHODS: We analyzed data from 11 Youth Risk Behavior Surveys conducted
      among representative samples of students in grades 9 through 12 in Massachusetts
      during 1995 to 2015. We used multivariable logistic regression models to identify
      trends over time by sexual identity. RESULTS: During 1995 to 2015, the prevalence
      of missing school decreased overall (from 5.6% to 4.8%) and among heterosexual
      (from 4.3% to 3.8%) and LGB (from 25.0% to 13.4%) students. The prevalence of
      having been threatened decreased overall (from 7.8% to 4.1%) and among
      heterosexual (from 6.5% to 3.5%) and LGB (from 32.9% to 6.7%) students.
      CONCLUSIONS: We identified evidence of a significant decrease in victimization
      among all students regardless of sexual identity and a steep decline among LGB
      students. Additional actions to improve school climate may help eliminate the
      disparities and decrease victimization for all youths.

PMID- 28520484
TI  - Fe en Accion: Promoting Physical Activity Among Churchgoing Latinas.
AB  - OBJECTIVES: To evaluate the impact of a faith-based intervention to promote
      physical activity in Latinas. METHODS: We randomized 16 churches in San Diego
      County, California, to a physical activity intervention or cancer screening
      comparison condition (n = 436). The intervention followed an ecological framework
      and involved promotoras. We examined 12-month intervention effects, including
      accelerometer-based moderate-to-vigorous physical activity (MVPA; primary
      outcome) and secondary outcomes. We conducted the study from 2010 to 2016.
      RESULTS: Mixed effects analyses showed significant increases in accelerometer
      based MVPA (effect size = 0.25) and self-report leisure-time MVPA (effect size =
      0.38) among Latinas in the intervention versus comparison condition. Participants
      in the intervention condition had about 66% higher odds of meeting the 2008
      Physical Activity Guidelines, had reduced body mass index (effect size = 0.23),
      and used more behavioral strategies for engaging in physical activity (effect
      size = 0.42). Program attendance was associated with increased self-reported
      leisure-time MVPA and the number of motivational interviewing calls was
      associated with meeting the 2008 Physical Activity Guidelines. CONCLUSIONS: A
      faith-based intervention was effective in increasing MVPA and decreasing body
      mass index among participants. Process analyses showed the value of program
      attendance and motivational interviewing calls.

PMID- 28520480
TI  - Review of Recent Methodological Developments in Group-Randomized Trials: Part 2
      Analysis.
AB  - In 2004, Murray et al. reviewed methodological developments in the design and
      analysis of group-randomized trials (GRTs). We have updated that review with
      developments in analysis of the past 13 years, with a companion article to focus
      on developments in design. We discuss developments in the topics of the earlier
      review (e.g., methods for parallel-arm GRTs, individually randomized group
      treatment trials, and missing data) and in new topics, including methods to
      account for multiple-level clustering and alternative estimation methods (e.g.,
      augmented generalized estimating equations, targeted maximum likelihood, and
      quadratic inference functions). In addition, we describe developments in analysis
      of alternative group designs (including stepped-wedge GRTs, network-randomized
      trials, and pseudocluster randomized trials), which require clustering to be
      accounted for in their design and analysis.

PMID- 28520487
TI  - Chemical Risk Assessment: Traditional vs Public Health Perspectives.
AB  - Preventing adverse health effects of environmental chemical exposure is
      fundamental to protecting individual and public health. When done efficiently and
      properly, chemical risk assessment enables risk management actions that minimize
      the incidence and effects of environmentally induced diseases related to chemical
      exposure. However, traditional chemical risk assessment is faced with multiple
      challenges with respect to predicting and preventing disease in human
      populations, and epidemiological studies increasingly report observations of
      adverse health effects at exposure levels predicted from animal studies to be
      safe for humans. This discordance reinforces concerns about the adequacy of
      contemporary risk assessment practices for protecting public health. It is
      becoming clear that to protect public health more effectively, future risk
      assessments will need to use the full range of available data, draw on innovative
      methods to integrate diverse data streams, and consider health endpoints that
      also reflect the range of subtle effects and morbidities observed in human
      populations. Considering these factors, there is a need to reframe chemical risk
      assessment to be more clearly aligned with the public health goal of minimizing
      environmental exposures associated with disease.

PMID- 28520488
TI  - Firearm Legislation and Fatal Police Shootings in the United States.
AB  - OBJECTIVES: To examine whether stricter firearm legislation is associated with
      rates of fatal police shootings. METHODS: We used a cross-sectional, state-level
      design to evaluate the effect of state-level firearm legislation on rates of
      fatal police shootings from January 1, 2015, through October 31, 2016. We
      measured state-level variation in firearm laws with legislative scorecards from
      the Brady Center, and for fatal police shootings we used The Counted, an online
      database maintained by The Guardian. RESULTS: State-level firearm legislation was
      significantly associated with lower rates of fatal police shootings (incidence
      rate ratio = 0.961; 95% confidence interval = 0.939, 0.984). When we controlled
      for sociodemographic factors, states in the top quartile of legislative strength
      had a 51% lower incidence rate than did states in the lowest quartile. Laws aimed
      at strengthening background checks, promoting safe storage, and reducing gun
      trafficking were associated with fewer fatal police shootings. CONCLUSIONS:
      Legislative restrictions on firearms are associated with reductions in fatal
      police shootings. Public Health Implications. Although further research is
      necessary to determine causality and potential mechanisms, firearm legislation is
      a potential policy solution for reducing fatal police shootings in the United
      States.

PMID- 28520489
TI  - Impact of the 2016 Ecuador Earthquake on Zika Virus Cases.
AB  - OBJECTIVES: To evaluate the impact of the April 2016 7.8-magnitude earthquake in
      Ecuador on the incidence of Zika virus (ZIKV) cases. METHODS: We used the
      national public health surveillance system for reportable transmissible
      conditions and included suspected and laboratory-confirmed ZIKV cases. We
      compared the number of cases before and after the earthquake in areas closer to
      and farther from the epicenter. RESULTS: From January to July 2016, 2234 patients
      suspected of having ZIKV infection were reported in both affected and control
      areas. A total of 1110 patients had a reverse transcription-polymerase chain
      reaction assay, and 159 were positive for ZIKV. The cumulative incidence of ZIKV
      in the affected area was 11.1 per 100 000 after the earthquake. The odds ratio of
      having ZIKV infection in those living in the affected area was 8.0 (95% CI = 4.4,
      14.6; P < .01) compared with the control area and adjusted for age, gender,
      province population, and number of government health care facilities.
      CONCLUSIONS: A spike in ZIKV cases occurred after the earthquake. Patients in the
      area closest to the epicenter had a delay in seeking care.

PMID- 28520490
TI  - Disparities in Disability by Educational Attainment Across US States.
AB  - OBJECTIVES: To examine how disparities in adult disability by educational
      attainment vary across US states. METHODS: We used the nationally representative
      data of more than 6 million adults aged 45 to 89 years in the 2010-2014 American
      Community Survey. We defined disability as difficulty with activities of daily
      living. We categorized education as low (less than high school), mid (high school
      or some college), or high (bachelor's or higher). We estimated age-standardized
      disability prevalence by educational attainment and state. We assessed whether
      the variation in disability across states occurs primarily among low-educated
      adults and whether it reflects the socioeconomic resources of low-educated adults
      and their surrounding contexts. RESULTS: Disparities in disability by education
      vary markedly across states-from a 20 percentage point disparity in Massachusetts
      to a 12-point disparity in Wyoming. Disparities vary across states mainly because
      the prevalence of disability among low-educated adults varies across states.
      Personal and contextual socioeconomic resources of low-educated adults account
      for 29% of the variation. CONCLUSIONS: Efforts to reduce disparities in
      disability by education should consider state and local strategies that reduce
      poverty among low-educated adults and their surrounding contexts.

PMID- 28520491
TI  - Firearm-Related Laws in All 50 US States, 1991-2016.
AB  - OBJECTIVES: To describe a new database containing detailed annual information on
      firearm-related laws in place in each of the 50 US states from 1991 to 2016 and
      to summarize key trends in firearm-related laws during this time period. METHODS:
      Using Thomson Reuters Westlaw data to access historical state statutes and
      session laws, we developed a database indicating the presence or absence of each
      of 133 provisions of firearm laws in each state over the 26-year period. These
      provisions covered 14 aspects of state policies, including regulation of the
      process by which firearm transfers take place, ammunition, firearm possession,
      firearm storage, firearm trafficking, and liability of firearm manufacturers.
      RESULTS: An examination of trends in state firearm laws via this database
      revealed that although the number of laws nearly doubled during the study period,
      there was substantial heterogeneity across states, leading to a widening
      disparity in the number of firearm laws. CONCLUSIONS: This database can help
      advance firearm policy research by providing 26 years of comprehensive policy
      data that will allow longitudinal panel study designs that minimize the
      limitations present in many previous studies.

PMID- 28520492
TI  - Use of a Digital Health Application for Influenza Surveillance in China.
AB  - OBJECTIVES: To examine whether a commercial digital health application could
      support influenza surveillance in China. METHODS: We retrieved data from the
      Thermia online and mobile educational tool, which allows parents to monitor their
      children's fever and infectious febrile illnesses including influenza. We modeled
      monthly aggregated influenza-like illness case counts from Thermia users over
      time and compared them against influenza monthly case counts obtained from the
      National Health and Family Planning Commission of the People's Republic of China
      by using time series regression analysis. We retrieved 44 999 observations from
      January 2014 through July 2016 from Thermia China. RESULTS: Thermia appeared to
      predict influenza outbreaks 1 month earlier than the National Health and Family
      Planning Commission influenza surveillance system (P = .046). Being younger, not
      having up-to-date immunizations, and having an underlying health condition were
      associated with participant-reported influenza-like illness. CONCLUSIONS: Digital
      health applications could supplement traditional influenza surveillance systems
      in China by providing access to consumers' symptom reporting. Growing popularity
      and use of commercial digital health applications in China potentially affords
      opportunities to support disease detection and monitoring and rapid treatment
      mobilization.

PMID- 28520493
TI  - Increasing Walking in the Hartsfield-Jackson Atlanta International Airport: The
      Walk to Fly Study.
AB  - OBJECTIVES: To test the effectiveness of a point-of-decision intervention to
      prompt walking, versus motorized transport, in a large metropolitan airport.
      METHODS: We installed point-of-decision prompt signage at 4 locations in the
      airport transportation mall at Hartsfield-Jackson Atlanta International Airport
      (Atlanta, GA) at the connecting corridor between airport concourses. Six ceiling
      mounted infrared sensors counted travelers entering and exiting the study
      location. We collected traveler counts from June 2013 to May 2016 when
      construction was present and absent (preintervention period: June 2013-September
      2014; postintervention period: September 2014-May 2016). We used a model that
      incorporated weekly walking variation to estimate the intervention effect on
      walking. RESULTS: There was an 11.0% to 16.7% relative increase in walking in the
      absence of airport construction where 580 to 810 more travelers per day chose to
      walk. Through May 2016, travelers completed 390 000 additional walking trips.
      CONCLUSIONS: The Walk to Fly study demonstrated a significant and sustained
      increase in the number of airport travelers choosing to walk. Providing signage
      about options to walk in busy locations where reasonable walking options are
      available may improve population levels of physical activity and therefore
      improve public health.

PMID- 28520494
TI  - Racial/Ethnic Disparities at the End of an HIV Epidemic: Persons Who Inject Drugs
      in New York City, 2011-2015.
AB  - OBJECTIVES: To examine whether racial/ethnic disparities persist at the "end of
      the HIV epidemic" (prevalence of untreated HIV infection < 5%; HIV incidence <
      0.5 per 100 person-years) among persons who inject drugs (PWID) in New York City.
      METHODS: We recruited 2404 PWID entering New York City substance use treatment in
      2001 to 2005 and 2011 to 2015. We conducted a structured interview, and testing
      for HIV and herpes simplex virus 2 (HSV-2; a biomarker for high sexual risk). We
      estimated incidence by using newly diagnosed cases of HIV. Disparity analyses
      compared HIV, untreated HIV, HIV-HSV-2 coinfection, HIV monoinfection, and
      estimated HIV incidence among Whites, African Americans, and Latinos. RESULTS: By
      2011 to 2015, Whites, African Americans, and Latino/as met both criteria of our
      operational "end-of-the-epidemic" definition. All comparisons that included HIV
      HSV-2-coinfected persons had statistically significant higher rates of HIV among
      racial/ethnic minorities. No comparisons limited to HIV monoinfected persons were
      significant. CONCLUSIONS: "End-of-the-epidemic" criteria were met among White,
      African American, and Latino/a PWID in New York City, but elimination of
      disparities may require a greater focus on PWID with high sexual risk.

PMID- 28520496
TI  - Shelter-Based Opioid Treatment: Increasing Access to Addiction Treatment in a
      Family Shelter.

PMID- 28520495
TI  - An Approach to Assess the Burden of Work-Related Injury, Disease, and Distress.
AB  - The true burden (morbidity, mortality, disability, cost, pain, distress) of
      occupational and work-related diseases and injuries is unknown, and what is
      reported as burden is significantly underestimated. This underestimation affects
      the way decision-makers view investments in research and worker protection, which
      in turn has a substantial impact on national welfare and public health. To better
      describe the societal and individual burdens of occupational and work-related
      diseases and injuries, we propose an approach to gauge what is known about burden
      and where new assessments may be made. This approach consists of 4 elements to
      consider in burden assessments: (1) utilizing multiple domains, including the
      individual worker, the worker's family, the community in which the workplace is
      located, the employer, and society as a whole; (2) taking a broader view of the
      work-relatedness of disease and injury; (3) assessing the impact of the entire
      working-life continuum; and (4) applying the comprehensive concept of "well
      being" as an indicator in addressing contemporary changes in the nature of work,
      the workplace, and the workforce. Further research on burden and enhanced
      surveillance is needed to develop these elements.

PMID- 28520497
TI  - LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a
      Sponge for miR-488-3p.
AB  - Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse
      diseases, including osteoarthritis (OA). The present study aims at exploring the
      biological role of lncRNA plasmacytoma variant translocation 1 (PVT1) in OA and
      the underlying mechanism. Results showed that the expression of PVT1 was
      upregulated in OA chondrocytes compared with normal chondrocytes, silencing PVT1
      inhibited the apoptosis of OA chondrocytes, and overexpression of PVT1 promoted
      the apoptosis of normal chondrocytes. To further investigate the underlying
      mechanism, miR-488-3p was predicted to be a targeted microRNA of PVT1. Different
      methods, including MS2 RNA immunoprecipitation (RIP), luciferase activity, and
      anti-AGO2 RIP, were performed to detect the interaction between PVT1 and miR-488
      3p, which suggested that PVT1 negatively regulated miR-488-3p in OA chondrocytes.
      Moreover, PVT1 promoted the apoptosis of OA and normal chondrocytes through miR
      488-3p. Collectively, this study revealed that lncRNA PVT1 regulated the
      apoptosis of chondrocytes by acting as a sponge for miR-488-3p in OA. PVT1 may be
      considered a new therapeutic target for the treatment of OA.

PMID- 28520498
TI  - Palliative Care and Parkinson's Disease: Caregiver Perspectives.
AB  - BACKGROUND: Palliative care for Parkinson's disease (PD) is an emerging area of
      interest for clinicians, patients and families. Identifying the palliative care
      needs of caregivers is central to developing and implementing palliative services
      for families affected by PD. The objective of this paper was to elicit PD
      caregiver needs, salient concerns, and preferences for care using a palliative
      care framework. MATERIALS AND METHODS: 11 PD caregivers and one non-overlapping
      focus group (n = 4) recruited from an academic medical center and community
      support groups participated in qualitative semi-structured interviews. Interviews
      and focus group discussion were digitally recorded, transcribed and entered into
      ATLAS.ti for coding and analysis. We used inductive qualitative data analysis
      techniques to interpret responses. RESULTS: Caregivers desired access to
      emotional support and education regarding the course of PD, how to handle
      emergent situations (e.g. falls and psychosis) and medications. Participants
      discussed the immediate impact of motor and non-motor symptoms as well as
      concerns about the future, including: finances, living situation, and caretaking
      challenges in advanced disease. Caregivers commented on the impact of PD on their
      social life and communication issues between themselves and patient. All
      participants expressed interest and openness to multidisciplinary approaches for
      addressing these needs. CONCLUSIONS: Caregivers of PD patients have considerable
      needs that may be met through a palliative care approach. Caregivers were
      receptive to the idea of multidisciplinary care in order to meet these needs.
      Future research efforts are needed to develop and test the clinical and cost
      effectiveness of palliative services for PD caregivers.

PMID- 28520500
TI  - Tracey.

PMID- 28520499
TI  - Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family:
      A Homology-Based Method.
AB  - The Enterobacteriaceae is a large family of Gram-negative, facultative anaerobic,
      non-spore forming rod-shaped bacteria that includes harmless and pathogenic
      organisms. The emergence and development of drug resistance in Enterobacteriaceae
      is complicating the treatment of serious infections. The aim of this study is to
      predict and characterize putative drug targets in Enterobacteriaceae family
      employing a homology-based computational method. The final putative drug targets
      were qualitatively characterized via cellular function prediction, subcellular
      localization prediction, broad-spectrum, and druggability analyses. Of 6,327
      analyzed proteins, 35 proteins were selected as final putative drug targets in
      Enterobacteriaceae family. These putative drug targets were involved in different
      vital pathways like metabolism, biosynthesis of macromolecule, and cell division.
      Predicted drug targets were also localized in the cytoplasm and cytoplasmic
      membrane of the pathogen that acts as antimicrobial or vaccine targets. Of 35
      drug targets, 5 targets were druggable and 30 targets were not druggable and were
      predicted as novel drug targets, which should be further evaluated to develop new
      antimicrobial. Thirteen drug targets were considered as broad-spectrum targets.
      It is expected that results of our study could facilitate the production of novel
      antibacterial for efficient treatment of infections caused by Enterobacteriaceae
      pathogens.

PMID- 28520501
TI  - Molecular Characterization of Multidrug-Resistant Escherichia coli Isolates from
      Bovine Clinical Mastitis and Pigs in the Vojvodina Province, Serbia.
AB  - The aim of the study was to characterize multidrug-resistant (MDR) Escherichia
      coli isolates collected in Serbia from bovine clinical mastitis cases and
      diseased pigs, mainly with molecular methods. A total of 48 E. coli isolates was
      collected during the years 2013-2014, of which 22 were MDR and were included in
      further analysis. Phylogenetic typing showed that 17 isolates belonged to group
      A, while two isolates were classified in group B1 and a single one in group D.
      All isolates showed unique macrorestriction patterns. Phenotypic susceptibility
      testing revealed resistances of the isolates against up to 13 antimicrobial
      agents, including resistance to fluoroquinolones. A wide variety of resistance
      genes was detected by PCR amplification and sequencing of amplicons. Sequence
      analysis of the quinolone resistance determining regions of topoisomerase genes
      revealed mutations in gyrA, parC, and/or parE. Plasmid-mediated quinolone
      resistance genes were detected in two porcine (aac-6'-Ib-cr and qnrS,
      respectively) isolates and a single bovine (aac-6'-Ib-cr) isolate. Resistance
      genes were found to be located on conjugative plasmids in 16 cases, many of which
      conferred a multidrug resistance phenotype. In conclusion, the plentitude of
      resistance genes located on conjugative plasmids and integrons in E. coli from
      cows and pigs in Vojvodina, Serbia, pose a high risk for horizontal gene transfer
      in bacteria from livestock husbandry.

PMID- 28520502
TI  - End-of-Life Care for Patients with Schizophrenia #332.

PMID- 28520504
TI  - Hope and Uncertainty in the Age of Miracles.

PMID- 28520503
TI  - Serum Alanine Aminotransferase Trends and Their Relationship with Obesity and
      Metabolic Syndrome in United States Adolescents, 1999-2014.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), characterized by
      hepatocyte dysfunction, fat accumulation, and fibrosis, is the most common cause
      of chronic liver disease in children. Elevated levels of serum alanine
      aminotransferase (ALT) are used clinically to identify potential liver
      dysfunction. Our goal was to assess for changes in the national prevalence of
      elevated ALT over time and potential relationship to trends in the metabolic
      syndrome (MetS) severity and elevated body mass index (BMI). MATERIALS AND
      METHODS: We studied 5411 non-Hispanic white, non-Hispanic black, and Hispanic
      adolescents aged 12-19 with complete MetS Z-score and ALT data from the National
      Health and Nutrition Examination Survey 1999-2014. Elevated ALT levels were
      defined by two different cutoffs: one for both sexes (30 U/L) and another that
      was sex specific (22 U/L girls; 25 U/L boys). MetS severity was assessed using a
      sex- and race-/ethnicity-specific MetS Z-score. RESULTS: We did not find a
      statistically significant linear increase in either mean ALT or the prevalence of
      elevated ALT differed over time. As expected, ALT levels were significantly
      correlated with BMI Z-score and MetS Z-score (P < 0.0001). Over time, BMI Z
      scores increased and MetS severity Z-score decreased. CONCLUSION: Prevalence of
      elevated ALT did not exhibit a linear change between 1999 and 2014 in U.S.
      adolescents, potentially due to divergent trends regarding BMI and MetS severity.
      Continued vigilance in monitoring BMI and ALT levels is advised for the U.S.
      adolescent population. MetS Z-score could act as an additional tool to monitor
      risk of elevated ALT and subsequent development of NAFLD.

PMID- 28520505
TI  - Early Blockade of Matrix Metalloproteinases in Spinal-Cord-Injured Dogs Results
      in a Long-Term Increase in Bladder Compliance.
AB  - Spinal cord injury (SCI) is often accompanied by reduced bladder compliance,
      which contributes to adverse conditions including urinary tract infections and
      vesicoureteral reflux. Reduced compliance is, in part, attributed to extensive
      remodeling of the bladder wall, including the extracellular matrix (ECM). Here,
      we tested the hypothesis that blockade of matrix metalloproteinases (MMPs), known
      for their ability to remodel the ECM, improves bladder compliance in dogs with
      SCI. We first evaluated dogs with naturally occurring SCIs resulting from
      intervertebral disc herniation (IVDH). After characterizing the natural history
      of urological recovery by cystometry in healthy dogs (n = 10) and dogs with SCIs
      (n = 20), we conducted a randomized, double-blinded, placebo-controlled clinical
      trial in dogs with IVDH-associated SCIs to assess the efficacy of the broad
      spectrum MMP inhibitor, GM6001, given within 48 h post-injury. The primary
      outcomes were bladder compliance, as measured by cystometry, and an ordinal gait
      score (Texas Spinal Cord Injury Score; TSCIS) at day 42 post-SCI. Dogs (n = 93)
      were randomized to receive either dimethyl sulfoxide (DMSO) or GM6001+DMSO. There
      were transient, but significantly (p = 0.023) greater, adverse events (31 of 42;
      74%) in the GM6001-treated group relative to vehicle controls (22 of 46; 48%).
      Whereas there were no differences in TSCIS between treatment groups at day 42 (p
      = 0.9679), bladder compliance was significantly higher in dogs treated with
      GM6001+DMSO compared to controls (p = 0.0272). Further studies are needed to
      determine whether this inhibition results from a direct interaction with the
      bladder wall or indirectly through neural-based mechanisms.

PMID- 28520506
TI  - Urinary nanovesicles captured by lectins or antibodies demonstrate variations in
      size and surface glycosylation profile.
AB  - AIM: The use of carbohydrate-binding proteins (lectins) to isolate urinary
      extracellular vesicles (uEVs) was investigated and the captured subpopulations
      were characterized. METHODS: Pooled uEVs from multiple healthy donors were
      exposed to lectin-conjugated or antibody-conjugated beads. Recovered uEVs were
      evaluated by protein estimation, transmission electron microscopy, nanoparticle
      tracking analysis and lectin microarray profiling. RESULTS: uEVs isolated by
      lectin- and antibody-based affinity capture exhibited distinct variations in size
      and surface content. Transmission electron microscopy confirmed similar EV
      diameters to those established by nanoparticle tracking analysis, but total
      particle counts did not correlate closely with protein-based quantification.
      Lectin microarray profiling demonstrated capture-dependent differences in surface
      glycosylation. CONCLUSION: Selective, carbohydrate-mediated EV isolation by
      lectin affinity approaches may prove immediately useful for research and find
      eventual use in clinical applications.

PMID- 28520507
TI  - Gold nanoparticles enhance the differentiation of embryonic stem cells into
      dopaminergic neurons via mTOR/p70S6K pathway.
AB  - AIM: This study aimed to investigate the effect of gold nanoparticles (AuNPs) on
      differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DA)
      neurons and explore the possible underlying molecular mechanisms. MATERIALS &
      METHODS: The efficiency of AuNPs on DA neuron differentiation was evaluated by
      observing fluorescence in TH promoter-engineered GFP-reporter ESCs, western blot
      and real-time PCR. The possible signal pathway was determined by western blot.
      RESULTS: Compared with feeder-free control condition, AuNPs are able to enhance
      fate specification of ESCs into DA neurons. Moreover, mTOR/p70S6K signaling
      pathway was found involving in this AuNPs-mediated DA neuron differentiation.
      CONCLUSION: Our findings may lead future insight investigation into the
      underlying mechanisms and potential application of AuNPs in stem cell research.

PMID- 28520510
TI  - Abstracts from The Aerosol Society Drug Delivery to the Lungs 27 Edinburgh
      International Conference Centre Edinburgh, Scotland, UK December 7-9, 2016.

PMID- 28520509
TI  - Recent advances in electrospun nanofibers for wound healing.
AB  - Electrospun nanofibers represent a novel class of materials that show great
      potential in many biomedical applications including biosensing, regenerative
      medicine, tissue engineering, drug delivery and wound healing. In this work, we
      review recent advances in electrospun nanofibers for wound healing. This article
      begins with a brief introduction on the wound, and then discusses the unique
      features of electrospun nanofibers critical for wound healing. It further
      highlights recent studies that have used electrospun nanofibers for wound healing
      applications and devices, including sutures, multifunctional dressings, dermal
      substitutes, engineered epidermis and full-thickness skin regeneration. Finally,
      we finish with conclusions and future perspective in this field.

PMID- 28520512
TI  - Zein nanoparticles as vehicles for oral delivery purposes.

PMID- 28520511
TI  - Upregulation of AcrEF in Quinolone Resistance Development in Escherichia coli
      When AcrAB-TolC Function Is Impaired.
AB  - We studied mechanisms of drug resistance development in Escherichia coli strains
      lacking efflux pump components. E. coli K12 deletion mutants were subjected to
      increasing concentrations of ciprofloxacin (CIP) to determine the frequency of
      target gene mutations. We generated a series of mutants that were selected based
      on their minimum inhibitory concentrations (MICs) to CIP, as well as their
      corresponding point mutations in target genes. The mutants displayed a number of
      target modifications and, in particular, gyrA mutations altering codons Ser83Leu,
      Asp87Gly, and Asp87His as well as a change in parC at 78 (substitution of Gly for
      Asp). All these mutations were related to drug resistance. When exposed to CIP,
      mutants lacking efflux pump genes acrA and acrB demonstrated a low level of
      resistance that was because of point mutations in the target genes. High-level
      resistance was achieved with a 100- to 500-fold increase in expression of efflux
      pump genes acrE and acrF that compensated for the loss of AcrA and AcrB, and thus
      resulted in an obvious increase of CIP MIC. We demonstrate that an intact AcrAB
      TolC efflux pump is crucial to the development of bacterial resistance. Its
      activity is complemented by expression of the alternative AcrEF efflux pump.

PMID- 28520513
TI  - Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent
      Chemotherapy and Radiation Therapy-A Hypothesis-generating Study.
AB  - Purpose To develop a system for assessment of tumor regression grade (TRG) with
      magnetic resonance (MR) imaging that is applicable to rectal mucinous
      adenocarcinoma (RMAC) and to obtain a preliminary evaluation of the association
      of MR imaging assessment of TRG with response to preoperative concurrent
      chemotherapy and radiation therapy (CCRT). Materials and Methods This
      retrospective study was approved by the institutional review board, and informed
      consent was waived. Pre- and post-CCRT MR images of 59 patients with RMAC (median
      age, 59 years; range, 29-80 years; 42 men [median age, 59 years; range, 36-80
      years] and 17 women [median age, 57 years; range, 29-79 years]) who underwent
      CCRT and subsequent elective resection from July 2005 to June 2015 were analyzed.
      Two experienced gastrointestinal radiologists independently analyzed imaging
      parameters such as T stage, mesorectal fascia status, extramural vascular
      invasion status, and TRG by using modified criteria developed for assessment of
      RMAC. Interobserver variability was calculated with weighted kappa analysis, and
      disagreement was settled in consensus. MR imaging TRG results were compared with
      those from pathologic TRG analysis (Mandard grade). Logistic regression analyses
      were performed to evaluate associations between imaging parameters and pathologic
      TRG. Results There was moderate to substantial agreement for imaging parameters
      (post-CCRT T stage-weighted kappa, 0.7134; post-CCRT mesorectal fascia status,
      0.618; TRG, 0.5023). Modified MR imaging TRG results were significantly
      associated with pathologic responsiveness (responsive group, Mandard grade 1 or
      2; nonresponsive group, Mandard grades 3-5; P = .023). Results of univariate and
      multivariate logistic regression analyses indicated that MR imaging TRG was the
      only factor significantly associated with CCRT responsiveness (univariate
      analysis, P = .023; multivariate analysis, P = .0261). Conclusion The modified MR
      imaging assessment of TRG was associated with treatment response to CCRT in
      patients with RMAC. (c) RSNA, 2017 Online supplemental material is available for
      this article.

PMID- 28520514
TI  - Flea and Small Mammal Species Composition in Mixed-Grass Prairies: Implications
      for the Maintenance of Yersinia pestis.
AB  - Maintenance of sylvatic plague in prairie dogs (Cynomis spp.) was once thought
      unlikely due to high mortality rates; yet more recent findings indicate that low
      level enzootic plague may be maintained in susceptible prairie dog populations.
      Another hypothesis for the maintenance of sylvatic plague involves small mammals,
      other than prairie dogs, as an alternative reservoir in the sylvatic plague
      system. These hypotheses, however, are not mutually exclusive, as both prairie
      dogs and small mammals could together be driving sylvatic cycles of plague. The
      concept of a bridging vector has been used to explain the transmission of
      pathogens from one host species to another. In the case of sylvatic plague, this
      would require overlap in fleas between small mammals and prairie dogs, and
      potentially other species such as carnivores. Our goal was to evaluate the level
      of flea sharing between black-tailed prairie dogs (Cynomis ludovicianus) and
      other small mammals in a mixed-grass prairie in South Dakota. We investigated the
      species richness of small mammals and small-mammal fleas in a mixed-grass prairie
      system and compared findings with previous studies from a short-grass ecosystem
      in Colorado. Over the summer field seasons 2014-2016 we live-trapped small
      mammals, collected fleas, and showed differences between both the flea and small
      mammal composition of the two systems. We also recorded higher densities of deer
      mice and lower densities of northern grasshopper mice in mixed versus shortgrass
      prairies. We confirmed, as is the case in shortgrass prairies, a lack of
      substantial flea species overlap on small mammal hosts and fleas from prairie
      dogs and their burrows. Moreover this study demonstrates that although small
      mammals may not play a large part in interepizootic plague cycling in shortgrass
      prairie ecosystems, their role in mixed-grass prairies requires further
      evaluation.

PMID- 28520515
TI  - Overcoming the tumor microenvironment: the role of nanohyperthermia.

PMID- 28520517
TI  - Nanoantibiotics: a new paradigm for the treatment of surgical infection.
AB  - Infections following orthopedic device implantations often impose a substantial
      health burden and result in high medical costs. Currently, preventative methods
      are often employed following an orthopedic implant to reduce risk of infection;
      however, contamination of the surgical site can still occur. Although antibiotics
      have demonstrated a substantial reduction in bacterial growth and maintenance,
      biofilm formation around the implant can often minimize efficacy of the
      antibiotic. Recently, nanotechnology has garnered significant interest, resulting
      in the development of several antibiotic delivery strategies that exhibit
      extended release and increased efficacy. In this review, treatment methods of
      orthopedic-device-related infections will be discussed and an overview of
      antimicrobial-based nanotechnologies will be provided. Specifically, nonmetal-,
      metal- and oxide-based nanotechnologies, incorporating antibacterial strategies,
      will be discussed.

PMID- 28520516
TI  - Mesenchymal Stem Cell Migration and Proliferation Are Mediated by Hypoxia
      Inducible Factor-1alpha Upstream of Notch and SUMO Pathways.
AB  - Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We
      and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha
      (HIF-1alpha) stabilization improves several MSC functions, including cell
      adhesion, migration, and proliferation, thereby increasing their therapeutic
      potential. To further explore the mechanisms induced by HIF-1alpha in MSCs, we
      studied its relationship with Notch signaling and observed that overexpression of
      HIF-1alpha in MSCs increased protein levels of the Notch ligands Jagged 1-2 and
      Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this
      pathway was activated. Crosstalk between HIF and Notch resulted in Notch
      dependent migration and spreading of MSCs, which was abolished by gamma-secretase
      inhibition. However, the HIF-1-induced increase in MSC proliferation was
      independent of Notch signaling. The ubiquitin family member, small ubiquitin-like
      modifier (SUMO), has important functions in many cellular processes and increased
      SUMO1 protein levels have been reported in hypoxia. To investigate the potential
      involvement of SUMOylation in HIF/Notch crosstalk, we measured general
      SUMOylation levels and observed increased SUMOylation in HIF-1-expressing MSCs.
      Moreover, proliferation and migration of MSCs were reduced in the presence of a
      SUMOylation inhibitor, and this effect was particularly robust in HIF-MSCs.
      Immunoprecipitation studies demonstrated SUMOylation of the intracellular domain
      of Notch1 (N1ICD) in HIF-1-expressing MSCs, which contributed to Notch pathway
      activation and resulted in increased levels of N1ICD nuclear translocation as
      assessed by subcellular fractionation. SUMOylation of N1ICD was also observed in
      HEK293T cells with stabilized HIF-1alpha expression, suggesting that this is a
      common mechanism in eukaryotic cells. In summary, we describe, for the first
      time, SUMOylation of N1ICD, which is potentiated by HIF signaling. These
      phenomena could be relevant for the therapeutic effects of MSCs in hypoxia or
      under conditions of HIF stabilization.

PMID- 28520518
TI  - Arrested Development: Infantile Hemangioma and the Stem Cell Teratogenic
      Hypothesis.
AB  - BACKGROUND: Early-life programming is defined by the adaptive changes made by the
      fetus in response to an adverse in utero environment. Infantile hemangioma (IH),
      a vascular anomaly, is the most common tumor of infancy. Here we take IH as the
      tumor model to propose the stem cell teratogenic hypothesis of tumorigenesis and
      the potential involvement of the immune system. OBJECTIVES: Teratogenic agents
      include chemicals, heavy metals, pathogens, and ionizing radiation. To
      investigate the etiology and pathogenesis of IH, we hypothesized that they result
      from a teratogenic mechanism. Immature, incompletely differentiated, dysregulated
      progenitor cells (multipotential stem cells) are arrested in development with
      vasculogenic, angiogenic, and tumorigenic potential due to exposure to
      teratogenic agents such as extrinsic factors that disrupt intrinsic factors via
      molecular mimicry. During the critical period of immunological tolerance,
      environmental exposure to immunotoxic agents may harness the teratogenic
      potential in the developing embryo or fetus and modify the early-life programming
      algorithm by altering normal fetal development, causing malformations, and
      inducing tumorigenesis. Specifically, exposure to environmental agents may
      interfere with physiological signaling pathways and contribute to the generation
      of IH, by several mechanisms. DISCUSSION: An adverse in utero environment no
      longer serves as a sustainable environment for proper embryogenesis and normal
      development. Targeted disruption of stem cells by extrinsic factors can alter the
      genetic program. CONCLUSIONS: This article offers new perspectives to stimulate
      discussion, explore novel experimental approaches (such as
      immunotoxicity/vasculotoxicity assays and novel isogenic models), and to address
      the questions raised to convert the hypotheses into nontoxic, noninvasive
      treatments.

PMID- 28520520
TI  - Three-Dimensional Cell Culture: A Rapidly Emerging Approach to Cellular Science
      and Drug Discovery.

PMID- 28520523
TI  - Making N-of-1 Medicine a Reality.

PMID- 28520519
TI  - Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.
AB  - BACKGROUND: Pregnancy rates among infertile women have been reported to increase
      after hysterosalpingography, but it is unclear whether the type of contrast
      medium used (oil-based or water-soluble contrast) influences this potential
      therapeutic effect. METHODS: We performed a multicenter, randomized trial in 27
      hospitals in the Netherlands in which infertile women who were undergoing
      hysterosalpingography were randomly assigned to undergo this procedure with the
      use of oil-based or water-based contrast. Subsequently, couples received
      expectant management or the women underwent intrauterine insemination. The
      primary outcome was ongoing pregnancy within 6 months after randomization.
      Outcomes were analyzed according to the intention-to-treat principle. RESULTS: A
      total of 1119 women were randomly assigned to hysterosalpingography with oil
      contrast (557 women) or water contrast (562 women). A total of 220 of 554 women
      in the oil group (39.7%) and 161 of 554 women in the water group (29.1%) had an
      ongoing pregnancy (rate ratio, 1.37; 95% confidence interval [CI], 1.16 to 1.61;
      P<0.001), and 214 of 552 women in the oil group (38.8%) and 155 of 552 women in
      the water group (28.1%) had live births (rate ratio, 1.38; 95% CI, 1.17 to 1.64;
      P<0.001). Rates of adverse events were low and similar in the two groups.
      CONCLUSIONS: Rates of ongoing pregnancy and live births were higher among women
      who underwent hysterosalpingography with oil contrast than among women who
      underwent this procedure with water contrast. (Netherlands Trial Register number,
      NTR3270 .).

PMID- 28520522
TI  - Perceptions of Statin Discontinuation among Patients with Life-Limiting Illness.
AB  - BACKGROUND: Optimal management of chronic medications for patients with life
      limiting illness is uncertain. Medication deprescribing may improve outcomes in
      this population, but patient concerns regarding deprescribing are unclear.
      OBJECTIVE: The aim of this study was to quantify the perceived benefits and
      concerns of statin discontinuation among patients with life-limiting illness.
      DESIGN: Baseline data from a multicenter, pragmatic clinical trial of statin
      discontinuation were used. SETTING/SUBJECTS: Cognitively intact participants with
      a life expectancy of 1-12 months receiving statin medications for primary or
      secondary prevention were enrolled. MEASUREMENTS: Responses to a 9-item
      questionnaire addressing patient concerns about discontinuing statins were
      collected. We used Pearson chi-square tests to compare responses by primary life
      limiting diagnosis (cancer, cardiovascular disease, other). RESULTS: Of 297
      eligible participants, 58% had cancer, 8% had cardiovascular disease, and 30%
      other primary diagnoses. Mean (standard deviation) age was 72 (11) years. Fewer
      than 5% of participants expressed concern that statin deprescribing indicated
      physician abandonment. About one in five participants reported being told to take
      statins for the rest of their life (18%) or feeling that discontinuation
      represented prior wasted effort (18%). Many participants reported benefits of
      stopping statins, including spending less money on medications (63%), potentially
      stopping other medications (34%), and having a better quality of life (25%). More
      participants with cardiovascular disease as a primary diagnosis perceived that
      quality-of-life benefits related to statin discontinuation (52%) than
      participants with cancer (27%) or noncardiovascular disease diagnoses (27%) [p =
      0.034]. CONCLUSION: Few participants expressed concerns about discontinuing
      statins; many perceived potential benefits. Cardiovascular disease patients
      perceived greater potential positive impact from statin discontinuation.

PMID- 28520525
TI  - Companion and Point-of-Care Sensor System for Rapid Multiplexed Detection of a
      Panel of Infectious Disease Markers.
AB  - A nanochannel-based electrochemical biosensor has been demonstrated for rapid and
      multiplexed detection of a panel of three biomarkers associated with rapid
      detection of sepsis. The label-free biosensor detected procalcitonin (PCT),
      lipoteichoic acid (LTA), and lipopolysaccharide (LPS) from human whole blood. The
      biosensor comprises a nanoporous nylon membrane integrated onto a microelectrode
      sensor platform for nanoconfinement effects. Charge perturbations due to
      biomarker binding are recorded as impedance changes using electrochemical
      impedance spectroscopy. The measured impedance change is used to quantitatively
      determine the concentration of the three biomarkers using antibody receptors from
      the tested sample. We were successful in detecting and quantifying the three
      biomarkers from whole blood. The limit of detection was 0.1 ng/mL for PCT and 1
      ug/mL for LPS and LTA. The sensor was able to demonstrate a dynamic range of
      detection from 01.1 ng/mL to 10 ug/mL for PCT and from 1 ug/mL to 1000 ug/mL for
      LPS and LTA biomarkers. This novel technology has promising preliminary results
      toward the design of sensors for rapid and sensitive detection of the three panel
      biomarkers in whole blood toward diagnosis and classification of sepsis.

PMID- 28520521
TI  - Three-Dimensional Cell Cultures in Drug Discovery and Development.
AB  - The past decades have witnessed significant efforts toward the development of
      three-dimensional (3D) cell cultures as systems that better mimic in vivo
      physiology. Today, 3D cell cultures are emerging, not only as a new tool in early
      drug discovery but also as potential therapeutics to treat disease. In this
      review, we assess leading 3D cell culture technologies and their impact on drug
      discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips,
      and 3D bioprinting. We also discuss the implementation of these technologies in
      compound identification, screening, and development, ranging from disease
      modeling to assessment of efficacy and safety profiles.

PMID- 28520528
TI  - Expanding the Roster of ROS1 Inhibitors.

PMID- 28520530
TI  - To Pump or Not to Pump in Pregnancy?

PMID- 28520529
TI  - Synthesis of theranostic epithelial cell adhesion molecule targeted mesoporous
      silica nanoparticle with gold gatekeeper for hepatocellular carcinoma.
AB  - AIM: In this study, we report the fabrication of epithelial cell adhesion
      molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica
      nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for
      theranostic applications. MATERIALS & METHODS: The prepared targeted and
      nontargeted formulations were evaluated in vitro in terms of their cellular
      internalization and toxicity. The prepared theranostic hybrid system was also
      implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo.
      RESULTS: Fluorescence microscopy and MTT assay demonstrated that the developed
      epithelial cell adhesion molecule-PEG-Au@Si-5-FU had higher cytotoxicity than
      nontargeted PEG-Au@Si-5-FU in 2D and 3D HepG2 cell cultures. Moreover, the
      targeted hybrid system was preferentially accumulated in HepG2 tumor cells in
      vitro and in vivo. CONCLUSION: This work introduces a novel strategy for
      developing multimodal NPs via nanoparticulate hybrid materials.

PMID- 28520526
TI  - KIR3DL1/ HL A-B Subtypes Govern Acute Myelogenous Leukemia Relapse After
      Hematopoietic Cell Transplantation.
AB  - Purpose Disease relapse remains a major challenge to successful outcomes in
      patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor
      natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but
      capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on
      leukemia cells-upregulated in the post-HCT environment-signals for NK cell
      inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and
      interrupts their antitumor activity. We hypothesized that varied strengths of
      inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA
      B, would titrate NK reactivity against acute myelogenous leukemia (AML). Patients
      and Methods By using an algorithm that was based on polymorphism-driven
      expression levels and specificities, we predicted and tested inhibitory and
      cytotoxic NK potential on the basis of KIR3DL1/HLA-B subtype combinations in
      vitro and evaluated their impact in 1,328 patients with AML who underwent HCT
      from 9/10 or 10/10 HLA-matched unrelated donors. Results Segregated by KIR3DL1
      subtype, NK cells demonstrated reproducible patterns of strong, weak, or
      noninhibition by target cells with defined HLA-B subtypes, which translated into
      discrete cytotoxic hierarchies against AML. In patients, KIR3DL1 and HLA-B
      subtype combinations that were predictive of weak inhibition or noninhibition
      were associated with significantly lower relapse (hazard ratio [HR], 0.72; P =
      .004) and overall mortality (HR, 0.84; P = .030) compared with strong inhibition
      combinations. The greatest effects were evident in the high-risk group of
      patients with all KIR ligands (relapse: HR, 0.54; P < .001; and mortality: HR,
      0.74; P < .008). Beneficial effects of weak and noninhibiting KIR3DL1 and HLA-B
      subtype combinations were separate from and additive to the benefit of donor
      activating KIR2DS1. Conclusion Consideration of KIR3DL1-mediated inhibition in
      donor selection for HLA-matched HCT may achieve superior graft versus leukemia
      effects, lower risk for relapse, and an increase in survival among patients with
      AML.

PMID- 28520531
TI  - Artificial Pancreas in Young Children.

PMID- 28520527
TI  - Open-Label, Multicenter, Phase II Study of Ceritinib in Patients With Non-Small
      Cell Lung Cancer Harboring ROS1 Rearrangement.
AB  - Purpose ROS1 rearrangement is a distinct molecular subset of non-small-cell lung
      cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients
      with ROS1-rearranged NSCLC. Patients and Methods We enrolled 32 patients with
      advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ
      hybridization. Ceritinib 750 mg was administered once daily. The primary end
      point was objective response rate. The secondary end points were disease control
      rate; duration of response; progression-free survival; overall survival;
      toxicity; and concordance among fluorescent in situ hybridization,
      immunohistochemistry, and next-generation sequencing. Results Between June 7,
      2013, and February 1, 2016, 404 patients underwent ROS1 prescreening, and 32
      patients with ROS1 rearrangement were enrolled. All patients except two were
      crizotinib-naive. At the time of data cutoff, the median follow-up was 14.0
      months, and 18 patients (56%) had discontinued treatment. Of the 32 patients
      enrolled, 28 were evaluable for response by independent radiologic review.
      Objective response rate was 62% (95% CI, 45% to 77%), with one complete response
      and 19 partial responses; duration of response was 21.0 months (95% CI, 17 to 25
      months); and disease control rate was 81% (95% CI, 65% to 91%). The median
      progression-free survival was 9.3 months (95% CI, 0 to 22 months) for all
      patients and 19.3 months (95% CI, 1 to 37 months) for crizotinib-naive patients.
      The median overall survival was 24 months (95% CI, 5 to 43 months). Of the eight
      patients with brain metastases, intracranial disease control was reported in five
      (63%; 95% CI, 31% to 86%). The most common adverse events (majority, grade 1 or
      2) for all treated patients were diarrhea (78%), nausea (59%), and anorexia
      (56%). Conclusion Ceritinib demonstrated potent clinical activity in patients
      with ROS1-rearranged NSCLC who were heavily treated previously with multiple
      lines of chemotherapy.

PMID- 28520532
TI  - Effectiveness of SmartGuard Technology in the Prevention of Nocturnal
      Hypoglycemia After Prolonged Physical Activity.
AB  - BACKGROUND: The prevention of postexercise nocturnal hypoglycemia after prolonged
      physical activity using sensor-augmented pump (SAP) therapy with predictive low
      glucose management (PLGM) has not been well studied. We conducted a study at a
      pediatric diabetes camp to determine whether a SAP with PLGM reduces the
      frequency of nocturnal hypoglycemia after prolonged physical activity more
      effectively than a SAP with a carbohydrate intake algorithm. METHODS: During a 1
      week sport camp, 20 children (aged 10-13 years) with type 1 diabetes (T1D)
      managed by SAP therapy either with (n = 7) or without PLGM (n = 13) were studied.
      The hypoglycemia management strategy and the continuous glucose monitoring
      (CGM)/PLGM settings were standardized. The incidence, severity, and duration of
      hypoglycemia and carbohydrate intake were documented and compared. RESULTS: The
      PLGM system was activated on 78% of all nights (once per night on average). No
      difference was found between the SAP and PLGM groups in the mean overnight
      glucose curve or mean morning glucose (7.8 +/- 2 mmol/L vs. 7.4 +/- 3 mmol/L).
      There was no difference in the frequency and severity of hypoglycemia. However,
      the SAP group consumed significantly more carbohydrates to prevent and treat
      hypoglycemia than those in the PLGM group; the values were 10 +/- 2 and 1 +/- 2
      gS (P < 0.0001) in the SAP and PLGM groups, respectively. Moreover, the SAP group
      spent a significantly longer time in hypoglycemia (64 +/- 2 min vs. 38 +/- 2 min,
      P < 0.05). We observed a difference in the time distribution of nocturnal
      hypoglycemia (10 to 12 p.m. in the PLGM group and 3 to 7 a.m. in the SAP group, P
      < 0.05). CONCLUSION: With PLGM system, euglycemia after prolonged physical
      activity was largely maintained with a minimal carbohydrate intake.

PMID- 28520533
TI  - A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay.
AB  - Zebrafish animal models lend themselves to behavioral assays that can facilitate
      rapid screening of ototoxic, otoprotective, and otoregenerative drugs.
      Structurally similar to human inner ear hair cells, the mechanosensory hair cells
      on their lateral line allow the zebrafish to sense water flow and orient head-to
      current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a
      dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby
      establishing itself as an excellent biomarker for anatomic damage to lateral line
      hair cells. Building on work by our group and others, we have built a new, fully
      automated high-throughput behavioral assay system that uses automated image
      analysis techniques to quantify rheotaxis behavior. This novel system consists of
      a custom-designed swimming apparatus and imaging system consisting of network
      controlled Raspberry Pi microcomputers capturing infrared video. Automated
      analysis techniques detect individual zebrafish, compute their orientation, and
      quantify the rheotaxis behavior of a zebrafish test population, producing a
      powerful, high-throughput behavioral assay. Using our fully automated biological
      assay to test a standardized ototoxic dose of cisplatin against varying doses of
      compounds that protect or regenerate hair cells may facilitate rapid translation
      of candidate drugs into preclinical mammalian models of hearing loss.

PMID- 28520534
TI  - CpG Island Methylation Correlates with the Use of Alternative Promoters for USP44
      Gene Expression in Human Pluripotent Stem Cells and Testes.
AB  - Deubiquitinating enzymes may play a major regulatory role in pluripotent stem
      cells (PSCs), but few studies have investigated this topic. Within this family of
      enzymes, we found that the ubiquitin-specific peptidase USP44, is highly
      expressed in embryonic stem cells, induced PSCs (iPSCs), and testes as compared
      with differentiated progenies and somatic organs. Analysis by quantitative
      polymerase chain reaction and 5' RACE showed that alternate promoters are
      responsible for expression in PSCs and organs. We noticed seven regions of
      transcription initiation, some of them with cell- or tissue-specific activity.
      Close analysis showed that one of the promoters involved in stem cell- and testis
      specific activity is differentially regulated in those tissues. At the epigenetic
      level, USP44 transcription was correlated with DNA methylation of a CpG island
      close to the main promoter region. These data imply a complex picture where
      regulating factors such as OCT4 may interact with other epigenetic mechanisms to
      regulate USP44 expression in PSCs and testes.

PMID- 28520535
TI  - Optimal Z-Score Use in Surgical Decision-Making in Pulmonary Atresia With Intact
      Ventricular Septum.
AB  - OBJECTIVES: In the surgical treatment of pulmonary atresia with intact
      ventricular septum, the size of the tricuspid valve annulus (as measured by z
      scores) has emerged as a significant factor in deciding which repair to perform.
      Various tricuspid valve annulus z-scores are reported as "cutoffs" for successful
      biventricular repair. We aimed to determine whether the use of different z-score
      data sets contributed to the gross variation in "cutoffs" for successful
      biventricular repair reported in the literature. METHODS: A single search was
      made of PubMed using the "advanced" setting with the following search terms:
      pulmonary, atresia, intact, septum, z, and score. The filters "title" and
      "title/abstract" were used for the first four and last two terms, respectively;
      the instruction "AND" combined all terms. Articles that identified which z-score
      data set was used in patients with biventricular repairs were included. RESULTS:
      From 13 articles, 1,392 patients were studied, 410 (29.5%) of which achieved
      biventricular repair. Three z-score data sets were quoted; mean tricuspid valve
      annulus z-scores in biventricular repair patients ranged between -0.53 and -5.1.
      After correcting for discrepancies between z-score data sets, no study reported a
      mean tricuspid valve annulus z-score <-2.8 in biventricular repair patients and
      83.3% reported mean tricuspid valve annuli z-scores >-1.7. CONCLUSION: The use of
      varied tricuspid valve annuli z-score data sets may have contributed to gross
      variations in reported "cutoffs" for successful biventricular repair. This could
      lead to inappropriate surgical pathway allocation.

PMID- 28520536
TI  - Anticoagulation for Interventional Extracardiac Fontan.

PMID- 28520537
TI  - Anomalous Origin of Right Coronary Artery From Left Coronary Sinus-13 Cases
      Treated With the Reimplantation Technique.
AB  - OBJECTIVES: Anomalous aortic origin of a coronary artery is uncommon but
      potentially clinically significant. Manifestations vary from asymptomatic
      patients to those who present with angina pectoris, myocardial infarction, heart
      failure, syncope, arrhythmias, and sudden death. We describe our experience with
      surgical reimplantation and results at midterm follow-up. METHODS: Between
      February 2003 and July 2016, a total of 13 patients with anomalous origin of the
      right coronary artery (RCA) from the left sinus underwent surgical
      reimplantation. RESULTS: Mean age was 39 years (range, 11-72 years). Eight
      patients presented with dyspnea and angina, two with acute myocardial infarction,
      and the remaining three were studied for atypical chest pain and ventricular
      premature contractions. Definitive diagnosis was achieved with coronary
      angiography in eight cases and with computed tomography scan in five. In all
      cases, the anomalous origin of the RCA from the left sinus had an intramural
      course except one case with interarterial (but not intramural) course. At
      operation, the RCA was dissected at the takeoff from the intramural course and
      reimplanted into the right sinus of Valsalva. There was no mortality. One patient
      had associated atherosclerotic coronary artery disease that required stent
      placement postoperatively. After a mean follow-up of 65 months (maximum 12
      years), all patients are asymptomatic and have returned to exercise without
      limitations. CONCLUSIONS: The reimplantation technique provides a good
      physiological and anatomical repair, eliminates a slit-like ostium, avoids
      compression of the coronary artery between the aorta and the pulmonary artery,
      and gives similar results to the unroofing technique.

PMID- 28520539
TI  - Left Ventricular Noncompaction With Muscular Ventricular Septal Defect in Mother
      and Son.

PMID- 28520538
TI  - Treatment Strategies for Paradoxical Hypertension Following Surgical Correction
      of Coarctation of the Aorta in Children.
AB  - BACKGROUND: Paradoxical hypertension after repair of coarctation of the aorta is
      a well-known phenomenon. The pathogenesis involves the activation of the
      sympathetic nervous system (first phase) and renin-angiotensin system (second
      phase). Only a limited number of different treatment strategies have been
      published in the literature, without any comparative studies. METHODS: Our aim
      was to describe the current international practice variation surrounding
      pharmacological treatment currently being employed to treat paradoxical
      hypertension following the repair of coarctation of the aorta in children. We
      performed an online survey among 197 members of the Pediatric Cardiac Intensive
      Care Society. We also conducted a systematic review of the literature regarding
      the treatment of paradoxical hypertension. RESULTS: Eighty-eight people (45%),
      from 62 different centers, responded and answered the questions regarding blood
      pressure control. Nitroprusside is the first drug of choice for initial blood
      pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and
      angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents.
      For oral blood pressure control after discharge from the pediatric intensive care
      unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta
      blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review
      identified 14 articles reporting pharmacological treatment of direct
      postoperative hypertension following coarctation repair. CONCLUSION: There is
      wide practice variability, due to the lack of sufficient compelling evidence. The
      majority (66%) of caregivers use nitroprusside to control blood pressure in the
      acute postoperative phase. The ACEIs are the drug of choice for chronic blood
      pressure control.

PMID- 28520540
TI  - Virtual Surgery for Conduit Reconstruction of the Right Ventricular Outflow
      Tract.
AB  - PURPOSE: Virtual surgery involves the planning and simulation of surgical
      reconstruction using three-dimensional (3D) modeling based upon individual
      patient data, augmented by simulation of planned surgical alterations including
      implantation of devices or grafts. Here we describe a case in which virtual
      cardiac surgery aided us in determining the optimal conduit size to use for the
      reconstruction of the right ventricular outflow tract. DESCRIPTION: The patient
      is a young adolescent male with a history of tetralogy of Fallot with pulmonary
      atresia, requiring right ventricle-to-pulmonary artery (RV-PA) conduit
      replacement. Utilizing preoperative magnetic resonance imaging data, virtual
      surgery was undertaken to construct his heart in 3D and to simulate the
      implantation of three different sizes of RV-PA conduit (18, 20, and 22 mm).
      EVALUATION: Virtual cardiac surgery allowed us to predict the ability to implant
      a conduit of a size that would likely remain adequate in the face of continued
      somatic growth and also allow for the possibility of transcatheter pulmonary
      valve implantation at some time in the future. Subsequently, the patient
      underwent uneventful conduit change surgery with implantation of a 22-mm Hancock
      valved conduit. As predicted, the intrathoracic space was sufficient to
      accommodate the relatively large conduit size without geometric distortion or
      sternal compression. CONCLUSION: Virtual cardiac surgery gives surgeons the
      ability to simulate the implantation of prostheses of different sizes in relation
      to the dimensions of a specific patient's own heart and thoracic cavity in 3D
      prior to surgery. This can be very helpful in predicting optimal conduit size,
      determining appropriate timing of surgery, and patient education.

PMID- 28520541
TI  - Outcomes and Prognostic Factors for Adult Patients With Congenital Heart Disease
      Undergoing Primary or Reoperative Systemic Atrioventricular Valve Surgery.
AB  - BACKGROUND: Adults with congenital heart disease (ACHD) undergoing systemic
      atrioventricular valve (SAVV) surgery are a complex, understudied population. We
      assessed midterm outcomes and prognostic factors in ACHD undergoing SAVV surgery.
      METHODS: We performed retrospective evaluation of ACHD undergoing SAVV surgery
      from January 2005 to February 2016: 14 (33%) patients with congenital mitral
      valve stenosis/regurgitation, 15 (35%) with atrioventricular septal defect
      (AVSD), and 14 (33%) with congenitally corrected transposition of the great
      arteries (ccTGA) with systemic tricuspid valve regurgitation. Adverse events were
      defined as mortality, reoperation on SAVV, and late more-than-moderate (>
      moderate) SAVV regurgitation. Statistical analysis was performed using Fisher's
      exact test and one-way analysis of variance as well as univariate and
      multivariate risk factor analysis. RESULTS: Fifteen (35%) patients had
      preoperative systemic ventricular dysfunction, including 13 patients with ccTGA
      (93%, P < .001). Twenty-three (54%) patients underwent valve repair, 20 (47%)
      patients underwent replacement, and 20 (47%) patients underwent an associated
      procedure. Replacement was higher in patients with ccTGA (86%) than the other
      groups ( P < 0.01). Thirty-seven patients (91% of survivors) were free of
      significant SAVV regurgitation at last follow-up, with patients with AVSD having
      greater regurgitation grades compared to the other groups ( P < 0.01). In
      hospital mortality, late mortality, late > moderate SAVV regurgitation, and SAVV
      reoperation rates were 5% (n = 2), 2% (n = 1), 9% (n = 3), and 7% (n = 3),
      respectively. On multivariate analysis, predischarge SAVV regurgitation grade was
      the only significant predictor of adverse events (odds ratio = 8.2, 95%
      confidence interval: 1.1-63.8, P = .045). CONCLUSION: Overall outcomes in this
      challenging population are good. The single factor associated with adverse events
      was predischarge SAVV regurgitation grade.

PMID- 28520542
TI  - Hybrid Palliation for Interrupted Aortic Arch With Small Aortic Valve.
AB  - OBJECTIVES: Open heart surgery for interrupted aortic arch in the neonatal period
      is still a high-risk procedure related in part to patient factors such as low
      birth weight, other morphologic anomalies, and, especially, small aortic valve
      size. Recently, we performed hybrid palliation with bilateral pulmonary artery
      banding and ductal stenting as the first-stage palliation for such cases. In this
      study, the outcomes of this procedure were examined. METHODS: Six cases of
      interrupted aortic arch with a small aortic valve underwent the hybrid procedure
      in the neonatal period in our institute from 2010 to 2015 (mean age: 6.8 days,
      mean body weight: 3.2 kg, mean z score of the aortic valve annulus: -8.3). Their
      postoperative clinical courses and results of the second-stage surgery were
      evaluated. RESULTS: No mortality or severe morbidity was seen in association with
      initial hybrid palliation. Five of six patients were discharged from the
      hospital; the one exception had a significant urinary tract anomaly. None needed
      an additional catheter intervention or surgical procedure postoperatively. All
      surviving patients underwent second-stage surgery; three had biventricular repair
      by the conventional method or Damus-Kaye-Stansel anastomosis with the Rastelli
      procedure and the other three proceeded toward staged Fontan reconstruction.
      Growth of the aortic valve was seen in four patients, and increased indexed left
      ventricle volume was recognized in one after the palliation. CONCLUSION: Hybrid
      palliation could be useful not only to avoid high-risk neonatal surgery but also
      to allow for eventual selection of the second-stage surgery based on the
      observations of potential interval development of left ventricular structures.

PMID- 28520543
TI  - Double Aortic Arch With a Retroaortic Innominate Vein: A Rare Association
      Diagnosed Using Cardiac Magnetic Resonance Imaging.

PMID- 28520544
TI  - Repair of Complete Atrioventricular Septal Defects With Decellularized
      Extracellular Matrix: Initial and Midterm Outcomes.
AB  - OBJECTIVE: Since April 2010, our institution has repaired complete
      atrioventricular septal defects (CAVSDs) with a two-patch technique utilizing
      CorMatrix extracellular material. This material is potentially an attractive
      patch because of its theorized eventual integration with the host tissue. We
      sought to analyze initial outcomes of CAVSD repair with CorMatrix. METHODS: Data
      were collected on consecutive pediatric (age <18) patients receiving two-patch
      CAVSD repairs with CorMatrix at a single institution from April 2010 to July
      2014. Baseline and perioperative characteristics were evaluated. Echocardiograms
      were evaluated in both the immediate postoperative period and the most recent
      postoperative follow-up. Variables analyzed included left AV valve performance,
      residual shunting, left ventricular outflow tract (LVOT) gradient, morbidity, and
      mortality. RESULTS: Fifteen patients were identified. The average age at
      operation was 205 days, with mean follow-up time at 1,364 days. Echocardiograms
      revealed the following: 12 (80%) patients showed either improved or stable left
      AV valve performance remaining at "mild" or less insufficiency, while two (13%)
      declined from "none" to mild and one (7%) from mild to "severe," which required
      reoperation. There was no residual shunting or LVOT obstruction at follow-up. The
      single (7%) reoperation was performed after three years due to left AV valve zone
      of apposition dehiscence. No permanent pacemakers were needed, and no deaths were
      reported. CONCLUSION: Our initial experience with CorMatrix in the repair of
      CAVSD in children has resulted in good initial and midterm outcomes. The
      CorMatrix patch remained stable through midterm follow-up, thus may be
      efficacious for use in CAVSD repair.

PMID- 28520546
TI  - A Simplified Technique for Interventional Extracardiac Fontan.

PMID- 28520545
TI  - Hemodynamic Profile of Acute Kidney Injury Following the Fontan Procedure: Impact
      of Renal Perfusion Pressure.
AB  - BACKGROUND: Acute kidney injury (AKI) is common following cardiopulmonary bypass.
      Fontan completion may result in systemic venous hypertension and low cardiac
      output, reducing renal perfusion pressure (RPP) and further increasing the risk
      of AKI. We investigated the incidence and risk factors for post-Fontan AKI.
      METHODS: Single-center retrospective study of children undergoing Fontan
      completion from 2005 to 2012. Demographic and hemodynamic variables were assessed
      for association with AKI. Subgroup analysis was performed on patients with high
      grade AKI (creatinine increase of >=2.0 * baseline). Vital sign data were
      collected hourly for the first postoperative day. RESULTS: A total of 186
      patients underwent Fontan at 3.1 (2.5-3.8) years of age and 13.5 kg (12.2-15.1).
      Acute kidney injury occurred in 97 (52%) patients, with high-grade AKI in 52
      (28%). Univariate analysis identified reduced RPP in patients with AKI compared
      to those without AKI, 50 (45-56) mm Hg versus 58 (54-61) mm Hg ( P < .0001), due
      to lower mean arterial blood pressure, 63 (60-69) versus 70 (66-73) mm Hg ( P <
      .0001), and higher central venous pressure, 14 (12-16) versus 13 (11-14) mm Hg, (
      p < .0001). Multivariable logistic regression and classification tree analyses
      further identified elements of RPP as significant predictors of AKI, especially
      high-grade AKI. Postoperative intubation was linked to AKI development. Patients
      with AKI had decreased postoperative urine output with increased colloid
      requirements, duration of chest tube insertion, and hospital length of stay.
      CONCLUSION: Acute kidney injury occurs frequently following the Fontan procedure.
      Associated factors include reduced RPP, high colloid requirements, and
      postoperative intubation. Targeted hemodynamic interventions may serve to reduce
      the incidence of post-Fontan AKI.

PMID- 28520547
TI  - Cardiovascular Magnetic Resonance of the Ross II Procedure: Long-Term
      Postoperative Imaging.

PMID- 28520548
TI  - Intracoronary Hypothermia Before Reperfusion to Reduce Reperfusion Injury in
      Acute Myocardial Infarction: A Novel Hypothesis and Technique.
AB  - Because current reperfusion strategies in acute myocardial infarction (AMI) seem
      to be exhausted in terms of additional mortality benefit, there remains a need
      for new methods to attenuate reperfusion injury and, thereby, further reduce
      myocardial infarct size and improve long-term survival. Therapeutic hypothermia
      (32-35 degrees C) diminishes reperfusion injury and reduces infarct size in a
      variety of animal models of AMI if provided before reperfusion. In human studies
      this reduction has not been confirmed so far, most likely because systemic
      cooling acts slowly, and therefore, the target temperature is not reached in time
      or at all in a substantial number of patients. Furthermore, systemic cooling can
      cause adverse effects such as severe shivering, volume overload, and an enhanced
      adrenergic state. In most randomized clinical trials, however, subgroups of
      patients with anterior myocardial infarction that reached the target temperature
      before reperfusion did show a reduction in infarct size. To transform therapeutic
      hypothermia into a clinically feasible treatment for AMI, its method must be
      modified. An ideal technique should be quick enough to achieve sufficient
      myocardial hypothermia before reperfusion, without significant delay and without
      the adverse effects of systemic cooling. In this review, we propose a novel,
      potentially feasible method of selective intracoronary hypothermia to overcome
      the problems encountered with prior techniques.

PMID- 28520551
TI  - Strategies for Sustained Weight Management: Perspectives From African American
      Patients With Type 2 Diabetes.
AB  - Purpose The purpose of this study was to identify effective strategies for
      sustained weight management used by African American patients with obesity and
      type 2 diabetes. Methods In this study, nominal group technique was used to
      identify effective strategies for weight management used by 12 African Americans
      with overweight/obesity and type 2 diabetes who successfully lost or maintained
      their weight after completing DECIDE (Decision-making Education for Choices In
      Diabetes Everyday), a 9-module, literacy-adapted diabetes and cardiovascular
      disease (CVD) education and problem-solving training program. Results
      Participants generated a list of 101 strategies that covered 4 domains:
      nutrition, physical activity, cognitive-behavioral strategies, and other. Self
      monitoring and relying on social support were the top 2 strategies for weight
      maintenance. Conclusion Future obesity studies should consider including
      friends/family as well as electronic tools to facilitate self-monitoring and
      regular practice of behavioral strategies for long-term success.

PMID- 28520550
TI  - Outcomes That Matter to Teens With Type 1 Diabetes.
AB  - Purpose The purpose of the study was to describe outcomes that matter to teens
      with type 1 diabetes. Understanding outcomes that matter to teens could support
      successful interventions to improve diabetes self-management. Methods Fifty
      publicly available posts published in the "teen" sections of 2 major diabetes
      online forums between 2011 and 2013 were analyzed using qualitative research
      methods. From each post, content and descriptive data (eg, duration of diabetes
      and age) were collected. Two members of the research team independently used open
      coding techniques to identify outcomes (defined as impacts or consequences of
      type 1 diabetes) and organized them into themes and subthemes. A codebook was
      jointly developed to facilitate the identification of meaningful outcomes from
      the posts. Results Teens' average age was 15.7 years, and the average time since
      diabetes diagnosis was 6.3 years. The 3 most commonly mentioned outcomes were (1)
      interactions with peers ("I want to talk to someone who understands"), (2)
      emotional well-being ("Diabetes makes me want to cry"), and (3) blood glucose
      management ("My blood sugar never goes down"). Other identified outcomes included
      (4) physical well-being, (5) education and motivation of others, (6) family
      interactions, (7) academic achievement, and (8) interactions with important
      others such as teachers. Conclusions While teens are concerned about control of
      their blood glucose, there are many other outcomes that matter to them. Health
      care providers and diabetes educators may want to consider these other outcomes
      when motivating teens with type 1 diabetes to improve blood glucose control.

PMID- 28520552
TI  - Prestimulus Inhibition of Saccades in Adults With and Without Attention
      Deficit/Hyperactivity Disorder as an Index of Temporal Expectations.
AB  - Knowing when to expect important events to occur is critical for preparing
      context-appropriate behavior. However, anticipation is inherently complicated to
      assess because conventional measurements of behavior, such as accuracy and
      reaction time, are available only after the predicted event has occurred.
      Anticipatory processes, which occur prior to target onset, are typically measured
      only retrospectively by these methods. In this study, we utilized a novel
      approach for assessing temporal expectations through the dynamics of prestimulus
      saccades. Results showed that saccades of neurotypical participants were
      inhibited prior to the onset of stimuli that appeared at predictable compared
      with less predictable times. No such inhibition was found in most participants
      with attention-deficit/hyperactivity disorder (ADHD), and particularly not in
      those who experienced difficulties in sustaining attention over time. These
      findings suggest that individuals with ADHD, especially those with sustained
      attention deficits, have diminished ability to benefit from temporal
      predictability, and this could account for some of their context-inappropriate
      behaviors.

PMID- 28520553
TI  - CDC's Public Health Surveillance of Cancer.
AB  - Routine data collection efforts are a necessary, often underappreciated,
      component of nearly all cancer research and prevention efforts. Public health
      cancer surveillance data are crucial for identifying needs, planning
      interventions, directing public health resources, and evaluating the overall
      effectiveness of initiatives aimed at preventing or treating cancer and its
      negative health consequences. As the nation's health protection agency, the
      Centers for Disease Control and Prevention (CDC) provides resources for disease
      surveillance systems to help protect our nation against expensive and dangerous
      health threats, including cancer. Therefore, public health surveillance is a core
      function of CDC. In this article we briefly describe CDC's approach to cancer
      surveillance in our public health programs and other federal initiatives to
      monitor cancer-related outcomes. We also describe our premier cancer incidence
      surveillance system, the National Program of Cancer Registries, and discuss uses
      and applications of the program's critical cancer data.

PMID- 28520555
TI  - Relaxation lifetimes of plasmonically enhanced hybrid gold-carbon nanotubes
      systems.
AB  - Recently, we introduced a novel hybridization route for carbon nanotubes using
      gold nanoparticles, whose close proximity neatly enhances their radiative
      emission. Here we investigate the mechanisms behind the enhancement by monitoring
      the de-excitation dynamics of our pi-hybrids through two-color pump-probe time
      resolved spectroscopy. The de-excitation process reveals a fast component and a
      slow component. We find that the presence of gold prominently affects the fast
      processes, indicating a stronger influence of the gold nanoparticle on the intra
      band non-radiative relaxation than on the inter-band recombination of the single
      walled carbon nanotube. By evaluating the de-excitation times, we estimate the
      balance between near-field pumping and the faster metal-induced de-excitation
      contributions, proving the enhanced pumping to be the leading mechanism.

PMID- 28520557
TI  - First-principles investigation of intrinsic defects and self-diffusion in ordered
      phases of V2C.
AB  - The self-diffusion behavior of vanadium subcarbide (V2C) is investigated using
      density functional theory calculations, owing to its potential application as a
      diffusion barrier in nuclear applications. Three ordered V2C structures, two of
      which correspond to experimentally observed phases, are characterized in terms of
      their equilibrium structural, electronic and elastic properties. Our model for
      self-diffusion in V2C considers diffusion of carbon and vanadium to occur
      separately on each sublattice. Two sets of self-diffusion coefficients are
      calculated for each structure: one for vacancy-mediated diffusion of vanadium and
      the other for interstitial diffusion of carbon. Calculated activation energies
      and diffusion prefactors are compared to experimental data for the cubic
      transition metal carbides as there is no experimental self-diffusion data for any
      of the hexagonal subcarbides.

PMID- 28520554
TI  - The Multiple Signals That Control Tuber Formation.

PMID- 28520556
TI  - Breast tissue stiffness estimation for surgical guidance using gravity-induced
      excitation.
AB  - Tissue stiffness interrogation is fundamental in breast cancer diagnosis and
      treatment. Furthermore, biomechanical models for predicting breast deformations
      have been created for several breast cancer applications. Within these
      applications, constitutive mechanical properties must be defined and the accuracy
      of this estimation directly impacts the overall performance of the model. In this
      study, we present an image-derived computational framework to obtain
      quantitative, patient specific stiffness properties for application in image
      guided breast cancer surgery and interventions. The method uses two MR
      acquisitions of the breast in different supine gravity-loaded configurations to
      fit mechanical properties to a biomechanical breast model. A reproducibility
      assessment of the method was performed in a test-retest study using healthy
      volunteers and was further characterized in simulation. In five human data sets,
      the within subject coefficient of variation ranged from 10.7% to 27% and the
      intraclass correlation coefficient ranged from 0.91-0.944 for assessment of
      fibroglandular and adipose tissue stiffness. In simulation, fibroglandular
      content and deformation magnitude were shown to have significant effects on the
      shape and convexity of the objective function defined by image similarity. These
      observations provide an important step forward in characterizing the use of
      nonrigid image registration methodologies in conjunction with biomechanical
      models to estimate tissue stiffness. In addition, the results suggest that
      stiffness estimation methods using gravity-induced excitation can reliably and
      feasibly be implemented in breast cancer surgery/intervention workflows.

PMID- 28520558
TI  - Data-driven event-by-event respiratory motion correction using TOF PET list-mode
      centroid of distribution.
AB  - Data-driven respiratory gating techniques were developed to correct for
      respiratory motion in PET studies, without the help of external motion tracking
      systems. Due to the greatly increased image noise in gated reconstructions, it is
      desirable to develop a data-driven event-by-event respiratory motion correction
      method. In this study, using the Centroid-of-distribution (COD) algorithm, we
      established a data-driven event-by-event respiratory motion correction technique
      using TOF PET list-mode data, and investigated its performance by comparing with
      an external system-based correction method. Ten human scans with the pancreatic
      beta-cell tracer 18F-FP-(+)-DTBZ were employed. Data-driven respiratory motions
      in superior-inferior (SI) and anterior-posterior (AP) directions were first
      determined by computing the centroid of all radioactive events during each short
      time frame with further processing. The Anzai belt system was employed to record
      respiratory motion in all studies. COD traces in both SI and AP directions were
      first compared with Anzai traces by computing the Pearson correlation
      coefficients. Then, respiratory gated reconstructions based on either COD or
      Anzai traces were performed to evaluate their relative performance in capturing
      respiratory motion. Finally, based on correlations of displacements of organ
      locations in all directions and COD information, continuous 3D internal organ
      motion in SI and AP directions was calculated based on COD traces to guide event
      by-event respiratory motion correction in the MOLAR reconstruction framework.
      Continuous respiratory correction results based on COD were compared with that
      based on Anzai, and without motion correction. Data-driven COD traces showed a
      good correlation with Anzai in both SI and AP directions for the majority of
      studies, with correlation coefficients ranging from 63% to 89%. Based on the
      determined respiratory displacements of pancreas between end-expiration and end
      inspiration from gated reconstructions, there was no significant difference
      between COD-based and Anzai-based methods. Finally, data-driven COD-based event
      by-event respiratory motion correction yielded comparable results to that based
      on Anzai respiratory traces, in terms of contrast recovery and reduced motion
      induced blur. Data-driven event-by-event respiratory motion correction using COD
      showed significant image quality improvement compared with reconstructions with
      no motion correction, and gave comparable results to the Anzai-based method.

PMID- 28520559
TI  - A comparative study of efficacy of single rooted and double rooted teeth in age
      estimation using dentin translucency.
AB  - BACKGROUND: Among various methods of age estimation using dental tissues,
      measurement of root dentin translucency (RDT) is said to be the most accurate.
      Numerous studies have estimated age by measuring RDT in single and double rooted
      teeth and have shown conflicting results. Only few studies have compared efficacy
      of using single and double rooted teeth for RDT measurement in age estimation.
      AIM: To analyze the efficacy of single rooted teeth (SRT) and double rooted teeth
      (DRT) for measurement of sclerotic dentin (SD) and age estimation. METHOD: Study
      was conducted on 120 freshly extracted SR and DR teeth with 60 teeth in each
      group. Ground sections of 150 u thickness were observed under stereomicroscope
      and photographed. The sclerotic dentin length was measured on the images captured
      using image analysis software. RESULTS AND CONCLUSION: The present study did not
      reveal significant difference (p = 0.012) between SRT and DRT when RDT was used
      for age estimation. However DRT provided more accurate age estimation than SRT
      with less mean age difference.

PMID- 28520560
TI  - Assessing age-related change in Japanese mental foramen opening direction using
      multidetector computed tomography.
AB  - OBJECTIVE: The purpose of this study was to investigate how the opening direction
      of the mental foramen (MF) changes with age in a Japanese population using multi
      detector computed tomography (MDCT). METHODS: Post-mortem MDCT scans of 121
      Japanese subjects (66 males and 55 females) were carried out where all subjects
      possessed at least twenty teeth, including molar teeth, in the upper and lower
      jaws. Two angles of the mental foramen opening were measured, namely the superior
      inferior angle in the coronal plane and anterior-posterior angle in the
      transverse plane, on the CT reconstructed images. The associations between age
      and these two angles were evaluated using a multiple regression analysis.
      RESULTS: For male subjects, the relationship between the superior-inferior angle
      and age was a quadratic curve (p < 0.001). This angle increased until the subject
      reached their early 50s and then the angle decreased with age. In the transverse
      plane, there was a linear relation between the anterior-posterior angle and age
      (p=0.002).It was noted also that the angle decreased with age. By contrast,
      however, no significant associations between the two angles and age for either
      measurement were noted for female subjects. This study demonstrated that the
      opening direction of the mental foramen changes with age in Japanese male
      subjects. By contrast this change in the opening direction of the mental foramen
      was not demonstrated in Japanese female subjects. In male subjects, the opening
      direction moves superiorly until the individual reaches their early 50s, and then
      moves inferiorly with advancing age. It also shifts from a posterior to an
      anterior position with age. CONCLUSION: These observed change differ from the
      results of previous studies. The findings could be useful for forensic science as
      they demonstrate a change in the position of mental foramen in a sample of
      contemporaneous male Japanese subjects.

PMID- 28520561
TI  - A comparative evaluation of the applicability of two adapted Haavikko methods for
      age estimation of 5-15 year old Indian children.
AB  - Dental age determination methods that require the assessment of all teeth are
      tedious and time-consuming. Adapted methods that assess fewer teeth may be more
      easily applicable. The present study compared the applicability of two adapted
      Haavikko methods which evaluate seven mandibular teeth (HAM1) and four reference
      teeth (HAM2) in a population of 5 to 15 year-old Indian children. The HAM1 method
      underestimated age by -0.17 +/- 0.80 years, -0.29 +/- 0.83 years and -0.22 +/-
      0.82 years in boys, girls and the total sample respectively, while the HAM2
      method underestimated age by -0.34 +/- 0.88 years, -0.51 +/- 0.82 years and -0.41
      +/- 0.86 years in boys, girls and the total sample, respectively. Significant
      gender-based differences were observed in mean DA-CA with both methods (p <
      0.05). While both methods could be used for age estimation of the present
      population, the HAM1 method was the more accurate of the two.

PMID- 28520563
TI  - Multiple deaths caused by a fire in a factory: identification and investigative
      issues.
AB  - The article presents a case of multiple casualties following a textile factory
      fire. The incident required a full DVI team similar to large mass-disaster
      because of the specific operational aspects and identification difficulties. The
      autopsy results were consistent with death by fire and the toxicological
      investigations revealed carbon monoxide poisoning in four cases (HbCO% ranging
      between 88,05 and 95,77), two deaths by cyanide intoxication (with concentrations
      between 5,17 and 8,85 mcg/ml), and in one case there was a synergistic effect of
      the two substances (carbon monoxide and cyanide). The identification, carried out
      in accordance with INTERPOL protocols, encountered serious difficulties in the AM
      phase primarily due to a language barrier and the lack of any dental or medical
      information relating to the victims. Secondary identifiers proved to be very
      useful in corroborating possible identities. As a result of the combined efforts
      of a team of experts the identity of each victim was determined and in all cases
      at least one primary identifier was used in the identification process. The
      deployment of DVI teams composed of forensic experts from different fields of
      expertise and well acquainted with DVI procedures, is essential in events
      involving multiple casualties that may also include foreign victims. The DVI team
      should intervene not only in PM examinations but also in the collection of AM
      data for those individuals not accounted for and by helping police in contacting
      families of missing people.

PMID- 28520562
TI  - Reliability and repeatability of pulp volume reconstruction through three
      different volume calculations.
AB  - OBJECTIVE: To test the variability of the volume measurements when different
      segmentation methods are applied in pulp volume reconstruction. MATERIALS AND
      METHODS: Osirix(r) and ITK-SNAP software were used. Different segmentation
      methods (Part A) and volume approaches (Part B) were tested in a sample of 21
      dental CBCT's from upper canines. Different combinations of the data set were
      also tested on one lower molar and one upper canine (Part C) to determine the
      variability of the results when automatic segmentation is performed. RESULTS:
      Although the obtained results show correlation among them(r > 0.75), there is no
      evidence that these methods are sensitive enough to detect small volume changes
      in structures such as the dental pulp canal (Part A and Part B). Automatic
      segmentation is highly susceptible to be affected by small variations in the
      setting parameters (Part C). CONCLUSIONS: Although the volumetric reconstruction
      and pulp/tooth volume ratio has not shown better results than methods based on
      dental radiographs, it is worth to persevere with the research in this area with
      new development in imaging techniques.

PMID- 28520564
TI  - Normothermic Cardiopulmonary Bypass in Patient With Waldenstrom's
      Macroglobulinemia and Cryoglobulinemia: A Case Report.
AB  - Waldenstrom's macroglobulinemia (WM) manifests as hyperviscosity syndrome.
      Cryoglobulinemia, which may increase blood viscosity or induce thrombosis in
      association with decreased body temperature, can occur in combination with WM. We
      describe the management of an 82-year-old woman with WM, hyperviscosity syndrome,
      and cryoglobulinemia who required open aortic valve replacement. Decreased body
      temperature in this patient was prevented during cardiopulmonary bypass by using
      a forced air warming system and normothermic cardioplegia with continuous warm
      blood cardioplegia perfusion.

PMID- 28520565
TI  - Use of a Tilting Orthopedic Fracture Table to Facilitate Proper Patient
      Positioning During Intrathecal Neurolysis With Hyperbaric Phenol: A Case Report.
AB  - We describe the case of a 41-year-old woman with metastatic cervical cancer and a
      large mass eroding into the pelvis and left lumbosacral plexus. The patient had
      intractable left lower extremity pain refractory to standard therapies, and she
      elected to undergo intrathecal neurolysis. A diagnostic intrathecal block was
      performed at the T11-12 interspace followed by intrathecal neurolysis with 6%
      phenol in glycerin on a subsequent date. During both procedures, we used a
      tilting radiolucent orthopedic fracture table to maintain strict left lateral
      supine positioning. A tilting orthopedic fracture table may be a valuable adjunct
      to ensure positional stability during intrathecal neurolysis.

PMID- 28520566
TI  - Essential Thrombocytosis and Labor Epidural Placement While on Aspirin: Assessing
      Hemorrhagic Risks: A Case Report.
AB  - Essential thrombocytosis (ET) is a rare disease with known thrombotic and
      bleeding complications. We encountered a patient with a diagnosis of longstanding
      Janus kinase-2 gene-negative ET on aspirin therapy presenting for labor epidural.
      Evaluation of platelet function with point-of-care analysis using Plateletworks
      in a community hospital setting allowed confirmation of adequate numbers of
      functional platelets to support safe epidural placement. The relevant issues of
      ET for anesthesia management with labor epidurals are discussed. Unique,
      relevant, and unexpected findings from the platelet function testing are
      presented.

PMID- 28520567
TI  - Persistent Hypotension and Cerebral Swelling Resulting From Mesenteric Traction
      Syndrome After Omental-to-Pial Pedicle Flap Transfer in a Young Woman With
      Refractory Moyamoya Disease: A Case Report.
AB  - Superficial temporal arterial to middle cerebral arterial anastomosis is often
      the initial surgical treatment of Moyamoya disease. In refractory cases, placing
      a pedicle flap of omentum over the ischemic brain has resulted in clinical
      improvement or stabilization of symptoms. We present a case of persistent
      mesenteric traction syndrome manifested by hypotension unresponsive to
      conventional doses of vasopressors during and after pulling the omentum to the
      brain. As prostacyclin is a major mediator of hypotension from mesenteric
      traction syndrome and also a cerebral vasodilator, we discuss the possibility
      that brain swelling may be a manifestation of mesenteric traction syndrome.

PMID- 28520568
TI  - Endothelin A receptor antagonists in diabetic kidney disease.
AB  - PURPOSE OF REVIEW: Despite optimal therapy of diabetic nephropathy with agents
      blocking the renin-angiotensin-aldosterone system, the residual risk of
      nephropathy progression to end-stage renal disease (ESRD) remains high. The
      purpose of this review is to discuss the potential role of endothelin antagonism
      as a therapeutic tool to reduce residual proteinuria and delay kidney injury
      progression among patients with diabetic nephropathy. RECENT FINDINGS:
      Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert
      proteinuria lowering and nephroprotective actions in experimental models of
      diabetic nephropathy. ERAs reduce proteinuria in phase 2 trials that included
      therapy with renin-angiotensin-aldosterone system blockers. Safety of these
      agents and protection from ESRD needs to be demonstrated in phase 3 trials.
      Excess risk of fluid retention and heart failure risk remains. SUMMARY: The
      hypothesis that the antiproteinuric effect of endothelin antagonism may be
      translated into a slower progression of diabetic nephropathy to ESRD is
      investigated in ongoing randomized trials assessing 'hard' renal endpoints. ERAs
      may represent a promising tool toward renoprotection in diabetic nephropathy by
      individualizing therapy and mitigating the risk of heart failure, if these trials
      are positive.

PMID- 28520569
TI  - The meaningness of colon cancer sidedness.

PMID- 28520570
TI  - Long-term exposure to MST-312 leads to telomerase reverse transcriptase
      overexpression in MCF-7 breast cancer cells.
AB  - Telomerase is an enzyme responsible for telomere maintenance in almost all human
      cancer cells, but generally not expressed in somatic ones. Therefore,
      antitelomerase therapy is a potentially revolutionary therapeutic strategy, and
      the antitumor activity of telomerase inhibitors (TI) has been studied extensively
      recently, mainly for breast cancer. However, the effects expected from treatment
      with TI will appear only after many cell divisions, but the effects of this long
      term approach are unknown. In this work, the consequences of 3120 h exposure of
      human breast cancer cells to TI MST-312 were investigated. MCF-7 cells were
      treated with MST-312 at a subtoxic concentration for a long time, and then cell
      morphology, viability, senescence, and proliferation were analyzed by phase
      contrast microscopy, MTT assay, beta-galactosidase test, and the trypan blue
      exclusion assay, respectively. Also, chromosomal stability was evaluated by
      classical cytogenetic analysis. The average length of telomeres and telomerase
      reverse transcriptase expression were accessed by real-time PCR and real-time RT
      PCR, respectively. The MST-312 showed cytotoxic action and promoted telomere
      erosion, senescence, and chromosome aberrations, as expected, but in a small
      proportion. Nevertheless, the proliferation rate of the culture was not affected.
      As the main effect, the chronic exposure led to cell adaptation by overexpression
      of telomerase in response to the inhibitor, which is a potential cause of
      therapeutic failure and may be associated with a poor prognosis. In conclusion,
      despite the high therapeutic potential of TIs such as MST-312, the molecular
      outcomes of long-term exposure of tumors on these drugs have to be evaluated when
      considering their clinical application, especially for breast cancer treatment.

PMID- 28520571
TI  - Is Omentectomy Mandatory Among Early Stage (I, II) Malignant Ovarian Germ Cell
      Tumor Patients? A Retrospective Study of 223 Cases.
AB  - OBJECTIVE: The aim of the study was to investigate whether omentectomy (OMT) is
      necessary in the operation for apparently early stage malignant ovarian germ cell
      tumors (MOGCTs). METHODS AND MATERIALS: Searching medical records database of Sun
      Yat-sen University Cancer Center from January 1, 1966, to November 30, 2015,
      patients with MOGCTs were identified and their age, year of diagnosis, tumor
      grade, histologic subtype, International Federation of Gynecology and Obstetrics
      stage, nodal findings, gross observation of omentum, and performance of OMT were
      assessed. Overall survivals of patients with or without OMT were compared using
      Kaplan-Meier survival curves. RESULTS: A total of 223 MOGCT cases with clinically
      early stage (stage I and II) disease and with the 3 common histological subtypes
      of MOGCT were obtained, which include yolk sac tumor (YST), dysgerminoma (DSG),
      and immature teratoma (IMT). There were 192 stage I cases and 31 stage II cases.
      Fifty-four patients were diagnosed with YST, 61 with DSG, and 108 with IMT.
      Omentectomy was performed as part of the initial surgery in 74.0% patients
      (165/223) and was omitted in 26.0% patients (58/223). Chemotherapy was
      administered in 88.3% (197/223) of all patients. The median follow-up was 82.0
      months. The 10-year overall survival rates of the patients with and without OMT
      were 90.5% and 98.1%, respectively (P = 0.156). Regarding different stages or
      histological subtypes, the 10-year survival rates of the 2 groups were 92.0%
      versus 97.9% (P = 0.324, stage I), 83.2% versus 100% (P = 0.351, stage II), 89.2%
      versus 100% (P = 0.303, YST), 94.1% versus 100% (P = 0.470, DSG), and 89.4%
      versus 96.0% (P = 0.405, IMT), respectively. CONCLUSIONS: In conclusion, OMT in
      patients with clinically early stage MOGCT may not improve patient survival and
      may be omitted.

PMID- 28520572
TI  - Maxillary Sinus Augmentation for Dental Implant Rehabilitation of the Edentulous
      Ridge: A Comprehensive Overview of Systematic Reviews.
AB  - OBJECTIVES: The objective of this systemic review was to perform a comprehensive
      overview of systematic reviews and meta-analyses of the maxillary sinus
      augmentation procedure for implant rehabilitation in humans. The following were
      evaluated in this overview: (1) anatomic variables affecting sinus augmentation,
      (2) histomorphometric analysis of the grafted sinus, (3) volumetric changes after
      sinus grafting, and (4) implant survival beyond 1 year. MATERIAL AND METHODS:
      Electronic databases were searched for systematic reviews and meta-analyses of
      implant-related sinus augmentation published from 1976 to September 2015. The
      studies selected must identify itself as a systemic review or meta-analysis in
      the title or abstract and must pertain to sinus augmentation. RESULTS: Thirty
      three publications fulfilled the review criteria. The AMSTAR ratings for the 33
      chosen reviews scored greater than 3 of 11, with 8 reviews scoring greater or
      equal to 8 of 11. CONCLUSION: The outcome of this overview suggested that the
      following will increase the success of sinus augmentation and survival of
      implants placed in the grafted sinus: (1) the use of barrier membranes over the
      lateral window when using a lateral approach to graft the sinus, (2) the use of
      particulate autogenous bone with or without other substitute graft materials, (3)
      sinus augmentation without the use of grafting materials may be considered
      provided that the space between the sinus membrane and floor can be maintained,
      (4) the use of rough-surfaced implants, (5) simultaneous implant placement with
      residual bone height greater than 4 mm, and (6) the cessation of smoking.

PMID- 28520573
TI  - Efficacy of non-invasive brain stimulation for people experiencing chronic pain.

PMID- 28520574
TI  - Orthotopic liver transplantation changes the course of gastric antral vascular
      ectasia: a case series from a transplant center.
AB  - BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is an important cause
      of upper gastrointestinal bleeding and anemia in patients with cirrhosis. The aim
      of our study was to evaluate the effect of orthotopic liver transplantation (OLT)
      on GAVE and associated anemia. PATIENTS AND METHODS: We performed a chart review
      and identified all cirrhotic patients with GAVE who underwent OLT at the
      University Of Alabama at Birmingham between 2005 and 2013. Population's
      demographics, etiology of cirrhosis, comorbidities, presentation and treatment
      modalities of GAVE, endoscopic and histopathologic reports, hemoglobin values
      before and after transplant, and immunosuppressive regimens were collected.
      RESULTS: Twelve patients were identified, mean age 52.4+/-4.4 years; seven were
      men (58.3%); 11 (91.7%) were White; and 6 of 12 patients had biopsy-proven GAVE.
      The most common etiology of cirrhosis in the cohort was chronic hepatitis C and
      obesity was the most common chronic condition in 50 and 83.3%, respectively.
      Anemia resolution was observed in 9/12 (75%) patients who underwent OLT with an
      increase in hemoglobin from 8.1+/-2.4 (5.7-13.1) before transplant to 12.0+/-1.4
      (10-15) after transplant (P<0.0001). Esophagogastroduodenoscopy after transplant
      was performed in all 12 (100%) patients. The mean time between transplant and
      post-OLT esophagogastroduodenoscopy was 13.8+/-18.28 (2-57) months; complete
      resolution of GAVE was observed in 10 (83.3%) patients, with resolving GAVE in
      one (8.3%) patient. CONCLUSION: GAVE is an important cause of anemia and upper
      gastrointestinal bleeding in patients with liver cirrhosis. Our findings show
      that liver transplantation can resolve GAVE and related anemia.

PMID- 28520576
TI  - Editor's Note: ANESTHESIOLOGY 2017: Expanding the Richness and Reach.

PMID- 28520575
TI  - Predictors of bile tree pathology in patients presenting with gallbladder
      disease.
AB  - BACKGROUND: Patients with gallstone disease can present with elevated liver
      function tests (LFTs). It is often challenging to differentiate those with a
      common bile duct (CBD) stone from those without a CBD stone on the basis of the
      LFTs levels. In this study, we aim to evaluate the predictors of a CBD stones
      among patients presenting with symptomatic gallbladder disease and elevated LFTs.
      PATIENTS AND METHODS: We retrospectively examined all patients who had undergone
      a cholecystectomy between January 2010 and December 2015. Patients with
      symptomatic cholelithiasis and increased LFTs were included. Patient
      characteristics, imaging findings, lab findings, endoscopic interventions, and
      operative report were recorded and evaluated. The diagnosis of CBD stones was
      made on the basis of ERCP and IOC findings. RESULTS: We included 354 patients in
      the final analysis. Of these, 113 (32%) had confirmed choledocholithiasis. The
      prevalence of CBD stones among biliary colic, acute cholecystitis, and
      pancreatitis patients was 47, 25, and 26%, respectively. gamma-Glutamyl
      transferase and direct bilirubin had the highest sensitivities for CBD stones
      among these patients (83 vs. 79%). In the setting of biliary colic, total
      bilirubin was highly predictive of CBD stones with a positive predictive value of
      85%. In the setting of acute cholecystitis, elevated LFTs were even less
      significant in predicting stones, with a positive predictive value of less than
      40% for most. CONCLUSION: Although gamma-glutamyl transferase and bilirubin
      levels showed a relatively higher sensitivity for CBDS compared with the other
      LFTs, these were not reliable enough because of high false-positive as well as
      false-negative values, especially in patients presenting with acute
      cholecystitis.

PMID- 28520577
TI  - The Effects of Remifentanil on Hemodynamic Response Attenuation After
      Electroconvulsive Therapy Under Sevoflurane Anesthesia.
AB  - PURPOSE: We evaluated the effects of a single loading dose of remifentanil (1
      MUg/kg) administered as an adjunct to sevoflurane, on the duration of seizure
      activity, recovery times, and hemodynamic profiles, during electroconvulsive
      therapy. METHODS: The patients were randomly allocated to receive sevoflurane
      saline (Group SS) or sevoflurane-remifentanil (Group SR). Sevoflurane (8%) was
      initiated for anesthesia induction in both groups until loss of consciousness was
      achieved. Remifentanil was then administered to Group SR via a 1-MUg/kg
      intravenous bolus. Patients in Group SS received saline in the same manner. Mean
      arterial pressure (MAP) and heart rate (HR) were recorded before anesthetic
      induction (T1), at the loss of consciousness (T2), and at 0, 1, 3, and 10 minutes
      after the electrical stimuli were completed (T3, T4, T5, and T6, respectively).
      RESULTS: Compared with the baseline values, HR increased significantly in Group
      SS at times T2 and T4 to T6 and decreased significantly in Group SR at time T2.
      When the groups were compared, we found that HR decreased significantly in Group
      SR at T2 and T4 to T6. Compared with baseline, MAP increased in Group SS between
      T3 and T6, and MAP decreased in Group SR at T2 and increased at T3 to T4. Mean
      arterial pressure decreased to a greater extent in Group SR than in Group SS
      during the T2 to T6 period. There were no group differences in seizure duration
      or recovery time. CONCLUSIONS: The addition of 1-MUg/kg remifentanil to
      anesthetic induction with sevoflurane attenuated the acute hemodynamic response
      to electroconvulsive therapy under sevoflurane anesthesia without adversely
      affecting the duration of seizure activity or the recovery profile.

PMID- 28520578
TI  - Robust Antidepressant Effect Following Alternating Intravenous Racemic Ketamine
      and Electroconvulsive Therapy in Treatment-Resistant Depression: A Case Report.

PMID- 28520581
TI  - Reply to: Accuracy of Consecutive Fecal Calprotectin Measurements to Predict
      Relapse in Inflammatory Bowel Disease Patients.

PMID- 28520580
TI  - High Agreement Between Benchtop and Point-of-Care Dipcard Tests for Ethyl
      Glucuronide.

PMID- 28520582
TI  - Intramedullary Nailing for Pilon Nonunions.
AB  - Nonunions are uncommon sequelae of tibial pilon fractures, but they can present a
      challenging problem to the treating surgeon. Treatment strategies can range from
      isolated bone grafting to revision plating depending on the type of nonunion and
      patient factors. Here, we present our technique and clinical results for
      intramedullary nailing of tibial pilon nonunions.

PMID- 28520579
TI  - The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic
      Machine Perfusion.
AB  - BACKGROUND: Normothermic machine perfusion of the liver (NMP-L) is a novel
      technique that preserves liver grafts under near-physiological conditions while
      maintaining their normal metabolic activity. This process requires an adequate
      oxygen supply, typically delivered by packed red blood cells (RBC). We present
      the first experience using an acellular hemoglobin-based oxygen carrier (HBOC)
      Hemopure in a human model of NMP-L. METHODS: Five discarded high-risk human
      livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC
      perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and
      histological features were compared during 6 hours of NMP-L. The cytotoxicity of
      Hemopure was also tested on human hepatic primary cell line cultures using an in
      vitro model of ischemia reperfusion injury. RESULTS: The vascular flow parameters
      and the perfusate lactate clearance were similar in both groups. The HBOC
      perfused livers extracted more oxygen than those perfused with RBCs (O2
      extraction ratio 13.75 vs 9.43 % *10 per gram of tissue, P = 0.001). In vitro
      exposure to Hemopure did not alter intracellular levels of reactive oxygen
      species, and there was no increase in apoptosis or necrosis observed in any of
      the tested cell lines. Histological findings were comparable between groups.
      There was no evidence of histological damage caused by Hemopure. CONCLUSIONS:
      Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP
      L perfusion fluid.

PMID- 28520583
TI  - Focal Capillary Dropout Associated With Optic Disc Drusen Using Optical Coherence
      Tomographic Angiography.
AB  - Optic disc drusen may be a cause of visual field defects and visual loss. The
      mechanism by which this occurs is unclear. We report a patient who developed
      decreased vision in the right eye and was found to have a heavy burden of
      superficial optic disc drusen. Optical coherence tomography (OCT) confirmed focal
      retinal nerve fiber layer thinning that corresponded with the distribution of
      drusen. OCT angiography, with superficial laminar segmentation, showed focal
      capillary attenuation overlying the most prominent drusen. These findings
      demonstrate alterations in the superficial retinal capillary network associated
      with optic disc drusen.

PMID- 28520585
TI  - The role of simulation and warm-up in minimally invasive gynecologic surgery.
AB  - PURPOSE OF REVIEW: The purpose of the review is to update the reader on the
      current literature and recent studies evaluating the role of simulation and warm
      up as part of surgical education and training, and maintenance of surgical
      skills. RECENT FINDINGS: Laparoscopic and hysteroscopic simulation may improve
      psychomotor skills, particularly for early-stage learners. However, data are
      mixed as to whether simulation education is directly transferable to surgical
      skill. Data are insufficient to determine if simulation can improve clinical
      outcomes. Similarly, performance of surgical warm-up exercises can improve
      performance of novice and expert surgeons in a simulated environment, but the
      extent to which this is transferable to intraoperative performance is unknown.
      Surgical coaching, however, can facilitate improvements in performance that are
      directly reflected in operative outcomes. SUMMARY: Simulation-based curricula may
      be a useful adjunct to residency training, whereas warm-up and surgical coaching
      may allow for maintenance of skill throughout a surgeon's career. These
      experiences may represent a strategy for maintaining quality and value in a lower
      volume surgical setting.

PMID- 28520584
TI  - Eating disorders and bone metabolism in women.
AB  - PURPOSE OF REVIEW: Eating Disorders are psychiatric disorders associated with a
      high risk for low bone mineral density (BMD) and fractures. Low BMD is a
      consequence of undernutrition, changes in body composition, and hormonal
      alterations. This review summarizes recent findings regarding novel strategies
      for assessing bone outcomes in patients with eating disorders, factors
      contributing to altered bone metabolism, and possible therapeutic strategies.
      RECENT FINDINGS: Emerging research in this field suggests that not only anorexia
      nervosa, but also bulimia nervosa results in lower BMD compared to controls. To
      date studies of bone structure, and all randomized controlled trials examining
      the impact of various therapies on bone outcomes in anorexia nervosa, have
      focused on adolescent girls and women. We discuss the impact of anorexia nervosa
      on bone structure, and associations of resting energy expenditure, marrow adipose
      tissue (including the ratio of saturated to unsaturated fat), and cold activated
      brown adipose tissue with BMD and bone structure. Promising strategies for
      treatment include physiological estrogen replacement (rather than oral
      contraceptives) in adolescent girls with anorexia nervosa, and bisphosphonates,
      as well as teriparatide, in adult women with anorexia nervosa. SUMMARY: Recent
      data on (i) BMD and bone structure in adolescent girls and women with eating
      disorders, (ii) factors that contribute to altered bone metabolism, and (iii)
      randomized controlled trials reporting positive effects of physiologic estrogen
      replacement, bisphosphonates and teriparatide on bone health, provide us with a
      greater understanding of the impact of eating disorders on bone and novel
      management strategies.

PMID- 28520587
TI  - Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in
      Preventing Gut Barrier Dysfunction Dependent on MLCK Activity.
AB  - BACKGROUND: Crohn's disease (CD) pathogenesis is multifactorial involving genetic
      and environmental factors. Loss of function mutations in the nucleotide
      oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD.
      Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune
      response and a defective mucosal barrier function evidenced by increased
      intestinal permeability. We previously showed that the latter is related to
      hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which
      Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments
      interplay to control epithelial paracellular permeability. METHODS: Depletion of
      CD4 T cells in Nod2 mice and treatments with inhibitors were conducted in
      chimeric mice transplanted with bone marrow cells from Nod2-deficient donors into
      Nod2-sufficient recipients or vice versa. Caco-2 cells overexpressing a NOD2 gene
      which did or did not include a CD-associated polymorphism were treated with
      inhibitors or siRNAs and cocultured with hematopoietic cells from Peyer's
      patches. RESULTS: In vivo and in vitro Nod2 in hematopoietic cells regulates
      epithelial paracellular permeability through cytokine production influencing
      myosin light chain kinase (MLCK) activity. Indeed, tumor necrosis factor-alpha
      and interferon-gamma secretion by CD4 T cells upregulated expression and activity
      of epithelial MLCK leading to increased epithelial tight junction opening. When
      stimulated by muramyl dipeptide, Nod2 in the nonhematopoietic compartment
      normalized the permeability and T-cell cytokine secretion and regulated MLCK
      activity. This MLCK regulation is mediated by TAK1 and RICK-dependent mechanisms.
      CONCLUSIONS: Our study demonstrates how hematopoietic and nonhematopoietic Nod2
      regulate intestinal barrier function, improving our knowledge on the mechanisms
      involved in CD pathogenesis.

PMID- 28520586
TI  - Clinical Course of Ulcerative Colitis After Liver Transplantation in Patients
      with Concomitant Primary Sclerosing Cholangitis and Ulcerative Colitis.
AB  - BACKGROUND: The natural history of ulcerative colitis (UC) after liver
      transplantation (LT) for primary sclerosing cholangitis (PSC) remains ill
      defined. This study aimed to evaluate the course of UC after LT for PSC. METHODS:
      The course of UC, including the clinical colitis severity index, was evaluated in
      patients with concomitant PSC and UC who received LT for PSC-induced end-stage
      liver disease. A total of 167 (55.4%) patients with PSC had concurrent
      inflammatory bowel disease (IBD). Of 159 cases of IBD that started before LT, 152
      (95.5%) had UC and 7 (4.5%) had Crohn's disease. RESULTS: The mean duration of
      patient follow-up after LT was 47.7 +/- 33.5 months. The simple clinical colitis
      activity index scores after LT showed no change in 15.8% of patients, decreased
      in 78.3%, and increased in 5.9%. Seventy-one (46.7%) patients required no change
      in their specific UC treatment after LT, whereas 12 (7.9%) had to use more
      aggressive treatments after LT. In 69 (45.4%) patients, treatment could be
      tapered although not discontinued. Multiple logistic regression analysis
      demonstrated that the duration of LT (odds ratio = 1.02; 95% confidence interval,
      1.00-1.05, P = 0.03) was significantly associated with aggravation in the
      clinical course of UC after LT. Posttransplant cyclosporine exposure (odds ratio
      = 0.14; 95% confidence interval, 0.015-0.79, P = 0.028) and pretransplant body
      weight (odds ratio = 0.81; 95% confidence interval, 0.71-0.93, P = 0.003)
      demonstrated a protective effect. CONCLUSIONS: Although the clinical course of UC
      remains unchanged or even improves in the majority of patients after LT, some may
      experience an aggressive course. The type of immunosuppression after
      transplantation can affect UC activity after LT. Cyclosporine may have some
      protective effects post-LT.

PMID- 28520588
TI  - Evaluation of the Quality of Semen and Sexual Function in Men with Inflammatory
      Bowel Disease.
AB  - BACKGROUND: Data on fertility rates and medication safety in men with
      inflammatory bowel disease (IBD) are limited. The aim of this study was to
      evaluate whether there is a seminal alteration in patients with IBD and, if so,
      to evaluate the mechanisms that may play a role according to what has been
      described in the literature. Its secondary aim was to evaluate the impact on male
      sexual function of IBD. METHODS: Multicenter, cross-sectional, case series study
      comparing men with IBD and control subjects. Semen analysis was performed
      according to the recommendations of World Health Organization. The impact on male
      sexual function was evaluated with the International Index of Erectile Function
      questionnaire. RESULTS: On multivariate analysis, patients with Crohn's disease
      had lower sperm concentrations compared with those with ulcerative colitis
      (median [interquartile range], 34.5 [19.2-48] versus 70 [34.5-127.5], P = 0.02)
      and lower seminal zinc levels (mean +/- SD, 1475 +/- 235 MUmol/L versus 2221 +/-
      1123 MUmol/L, P = 0.04). Patients with Crohn's disease on anti-tumor necrosis
      factor treatment had better progressive motility (mean +/- SD, 56.7 +/- 17.7
      versus 35.1 +/- 22.1, P = 0.01) and sperm morphology (14.4 +/- 7.1 versus 7.6 +/-
      4.9, P = 0.04) than those who were not on anti-tumor necrosis factor. Regarding
      sexual function, no significant differences were found across patients with IBD
      and control subjects. CONCLUSIONS: Men with Crohn's disease showed a trend toward
      poorer semen quality than those with ulcerative colitis. Treatment with anti
      tumor necrosis factor drugs does not seem to be associated with poor sperm
      quality. In patients in clinical remission, male sexual function is not affected
      by IBD.

PMID- 28520589
TI  - Distance to Specialist Care and Disease Outcomes in Inflammatory Bowel Disease.
AB  - BACKGROUND: Optimal treatment of inflammatory bowel disease (IBD) requires
      specialized health care. Patients frequently travel long distances to obtain care
      for IBD, which may hinder regular care and affect outcomes adversely. METHODS:
      This study included patients with established Crohn's disease or ulcerative
      colitis receiving care at a single referral center between January 2005 and
      August 2016. Distance to our health care center from the zip code of residence
      was determined for each patient and classified into quartiles. Our primary
      outcome was need for IBD-related surgery with secondary outcomes being need for
      biological and immunomodulator therapy. Logistic regression models adjusting for
      relevant covariates examined the independent association between travel distance
      and patient outcomes. RESULTS: Our study included 2136 patients with IBD (1197
      Crohn's disease, 939 ulcerative colitis), among which just over half were women
      (52%), and the mean age was 41 years. The mean distance from our hospital was
      2.5, 8.8, 22.0, and 50.8 miles for the first (most proximal) through fourth (most
      distant), respectively. We observed a statistically significant and meaningful
      higher risk among patients in the most distant quartile in the need for
      immunomodulator use (OR, 1.69; 95% CI, 1.29-2.22), biological therapy (OR, 2.19;
      95% CI, 1.69-2.85), and surgery (OR, 2.44; 95% CI, 1.80-3.32). Differences
      remained significant on multivariable analysis and by type of IBD. CONCLUSIONS:
      Greater distance to referral health care center was associated with increased
      risk for needing IBD-related surgery in patients with Crohn's disease or
      ulcerative colitis.

PMID- 28520590
TI  - Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from
      bench to bedside.
AB  - PURPOSE OF REVIEW: Treatment of aggressive pituitary tumours often yields
      suboptimal control of the tumour and confers significant morbidity. Lactotroph
      and corticotroph-derived tumours express ErbB receptors and ligands, and
      mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth
      factor receptor (EGFR) degradation, have been implicated in Cushing disease
      pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a
      potential new therapeutic approach for patients with aggressive prolactinomas and
      Cushing disease. RECENT FINDINGS: Using EGFR or human epidermal growth factor
      receptor 2-driven prolactin (PRL) promoters, transgenic mice develop large
      tumours that respond to TKI inhibition. In human corticotroph primary cultures,
      treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib
      suppresses proopiomelanocortin mRNA. USP8 mutations, detected in up to two-thirds
      of Cushing disease, may underlie the increase in EGFR signalling in these
      tumours. Human prolactinomas have differential ErbB receptor expression
      associated with aggressive behaviour and data from an ongoing clinical trial
      suggest that resistant prolactinomas may respond to the EGFR TKI lapatinib.
      SUMMARY: Preclinical and clinical models substantiate the role of the EGFR
      pathway in corticotroph and lactotroph adenomas. Although further study is
      needed, results to date suggest that targeting the ErbB pathway may be an
      effective therapeutic approach for patients with aggressive pituitary tumours.

PMID- 28520591
TI  - Stem cell therapy and its potential role in pituitary disorders.
AB  - PURPOSE OF REVIEW: The pituitary gland is one of the key components of the
      endocrine system. Congenital or acquired alterations can mediate destruction of
      cells in the gland leading to hormonal dysfunction. Even though pharmacological
      treatment for pituitary disorders is available, exogenous hormone replacement is
      neither curative nor sustainable. Thus, alternative therapies to optimize
      management and improve quality of life are desired. RECENT FINDINGS: An
      alternative modality to re-establish pituitary function is to promote endocrine
      cell regeneration through stem cells that can be obtained from the pituitary
      parenchyma or pluripotent cells. Stem cell therapy has been successfully applied
      to a plethora of other disorders, and is a promising alternative to hormonal
      supplementation for resumption of normal hormone homeostasis. SUMMARY: In this
      review, we describe the common causes for pituitary deficiencies and the advances
      in cellular therapy to restore the physiological pituitary function.

PMID- 28520592
TI  - Validation of the A&D UM-211 device for office blood pressure measurement
      according to the European Society of Hypertension International Protocol revision
      2010.
AB  - The aim of this study was to define the accuracy of UM-211, an automated
      oscillometric device for office use coupled to several cuffs for different arm
      sizes, according to the International Protocol of the European Society of
      Hypertension. The validation was performed in 33 individuals. Their mean age was
      59.6+/-12.9 years, systolic blood pressure (BP) was 144.3+/-21.5 mmHg (range: 96
      184 mmHg), diastolic BP was 86.8+/-18.5 mmHg (range: 48-124 mmHg), and arm
      circumference was 30.2+/-4.3 cm (range: 23-39 cm). Four sequential readings were
      taken by observers 1 and 2 using a double-headed stethoscope and a mercury
      sphygmomanometer, whereas three BP readings were taken by the supervisor using
      the test instrument. The differences between the readings provided by the device
      and the mean observer measurements were calculated. Therefore, each device
      measurement was compared with the previous and the next mean observer
      measurement. The validation results fulfilled all the 2010 European Society of
      Hypertension revision Protocol criteria for the general population and passed all
      validation grades. On average, the device overestimated systolic BP by 1.7+/-2.4
      mmHg and diastolic BP by 1.7+/-2.5 mmHg. These data show that the UM-211 device
      coupled to several cuffs for different ranges of arm circumference met the
      requirements for validation according to the International Protocol and can be
      recommended for clinical use in the adult population. However, these results
      mainly apply to the use of the 22-32 and the 31-45 cm cuffs.

PMID- 28520593
TI  - Strengthening Health Systems to Provide Rehabilitation Services.

PMID- 28520594
TI  - AmpliVue Is a Practical and Timely Test for the Detection of HSV From Keratitis
      Specimens.
AB  - OBJECTIVE: The laboratory diagnostic detection of herpes simplex virus (HSV) from
      eye samples must be practical, timely, and definitive for appropriate therapy.
      Although polymerase chain reaction (PCR) and/or cell culture can be definitive,
      HSV results can be delayed. Enzyme Linked Virus Inducible System (ELVIS) is a
      test that can provide results within 24 to 48 hr. We evaluated "AmpliVue HSV 1+2
      Assay" as a molecular colorimetric test that can detect HSV (1 or 2) DNA within 1
      hr. METHODS: Cornea/conjunctival samples were tested retrospectively with
      AmpliVue against 53 true-positive and 20 true-negative specimens collected in
      chlamydial transport medium. All clinical specimens were tested by cell culture
      isolation, PCR, and ELVIS for routine patient care. RESULTS: The sensitivity of
      AmpliVue against ocular samples that were both culture-positive and PCR-positive
      was 84%. The specificity of AmpliVue was 100%. Only one clinical sample was HSV-2
      positive, whereas all others tested positive for HSV-1. Based on PCR-positive and
      cell culture-negative samples, AmpliVue (11 of 17) tested more positive than
      ELVIS (0 of 17) (P=0.003, Fisher Exact). CONCLUSIONS: AmpliVue is moderately
      sensitive and highly specific as a practical and timely diagnostic test for
      detecting ocular HSV. Expertise is readily achieved and the test is
      straightforward with easy interpretation. Negative AmpliVue testing must be
      confirmed with PCR. AmpliVue has potential as an office-based diagnostic test.

PMID- 28520595
TI  - Decreased Visual Acuity by an Irregular Corneal Posterior Surface After Repeat
      Descemet Stripping Automated Endothelial Keratoplasty.
AB  - PURPOSE: To investigate the impact of higher-order aberrations (HOAs) on visual
      acuity after repeat Descemet stripping automated endothelial keratoplasty (DSAEK)
      in the same eyes. METHODS: This retrospective comparative case series includes 23
      patients who underwent DSAEK twice in the same eyes (46 DSAEK in total). We
      evaluated the HOAs of the anterior and posterior corneal surfaces, and total
      cornea using the Fourier analysis data from anterior segment optical coherence
      tomography. Eyes were divided into one of the following groups, based on the
      improvement and decline in the best-corrected visual acuity (BCVA) after repeat
      DSAEK; group A: 12 eyes with an improvement >= 2 lines, group B: 12 eyes with a
      decline <= 2 lines, and group C: 11 eyes with no change or change within 1 line.
      RESULTS: The HOAs of the posterior surface in group B were significantly greater
      than those of group A (P=0.028), whereas there were no significant differences in
      the anterior surface and total corneal HOAs between groups A and B (P=0.12 and
      0.08). There were no significant differences in the anterior and posterior
      surface as well as total cornea HOAs between initial DSAEK and repeat DSAEK in
      group C (P=0.87, 0.65, and 0.42). The postoperative BCVA had a significant
      correlation with the HOAs of the anterior and posterior surfaces as well as the
      total cornea (R=0.40, 0.46, and 0.53; P=0.01, 0.002, and 0.001). CONCLUSIONS:
      Posterior corneal HOAs can have a negative influence on the visual acuity after
      endothelial keratoplasty.

PMID- 28520596
TI  - Fungal Keratitis Associated With Airborne Organic Debris and Soft Contacts
      Lenses: Case Reports and Review of the Literature.
AB  - OBJECTIVES: To report two cases of fungal keratitis in soft contact lens wearers
      who were exposed to environmental mold. METHODS: Case reports, with review of the
      relevant literature. RESULTS: Two otherwise healthy middle-aged women who were
      soft contact lens wearers developed fungal keratitis about 1 week after heavy
      exposure to environmental mold. Culture results showed Aspergillus from one
      patient and the unusual combination of Trichoderma and Penicillium from the
      other. Both were treated with topical natamycin, topical fluoroquinolone
      antibiotic prophylaxis, and periodic ulcer debridement. After many weeks of
      treatment, both ulcers healed with subsequent scarring. Because the ulcers were
      located in the peripheral cornea in both cases, excellent final visual acuities
      were achieved. Fungal keratitis cases like these are rarely seen at our referral
      clinic, which is located in the temperate climate of northeastern Indiana.
      CONCLUSIONS: In addition to the usual recommended contact lens care guidelines,
      it may be prudent for eye care providers to warn patients against wearing their
      contact lenses in situations likely to result in heavy exposure to organic matter
      or, at the very least, to wear tight-fitting goggles for eye protection.

PMID- 28520597
TI  - Key performance indicators' assessment to develop best practices in an Emergency
      Medical Communication Centre.
AB  - INTRODUCTION: Emergency Medical Communication Centre (EMCC) represents a pivotal
      link in the chain of survival for those requiring rapid response for out-of
      hospital medical emergencies. Assessing and grading the performance of EMCCs are
      warranted as it can affect the health and safety of the served population.
      OBJECTIVE: The aim of our work was to describe the activity on an EMCC and to
      explore the associations between different key performance indicators. METHODS:
      We carried out our prospective observational study in the EMCC of Nantes, France,
      from 6 June 2011 to 6 June 2015. The EMCC performance was assessed with the
      following key performance indicators: answered calls, Quality of Service 20 s
      (QS20), occupation rate and average call duration. RESULTS: A total of 35 073 h
      of dispatch activity were analysed. 1 488 998 emergency calls were answered. The
      emergency call incidence varied slightly from 274 to 284 calls/1000 citizens/year
      between 2011 and 2015. The median occupation rate was 35% (25-44). QS20 was
      correlated negatively with the occupation rate (Spearman's rho: -0.78). The
      structural equation model confirmed that the occupation rate was highly
      correlated with the QS20 (standardized coefficient: -0.89). For an occupation
      rate of 26%, the target value estimated by our polynomial model, the probability
      of achieving a QS20 superior or equal to 95% varied between 56 and 84%.
      CONCLUSION: The occupation rate appeared to be the most important factor
      contributing towards the QS20. Our data will be useful to develop best practices
      and guidelines in the field of emergency medicine communication centres.

PMID- 28520599
TI  - Healing by Intention.

PMID- 28520602
TI  - Medical Nutrition Therapy, Obesity Behavioral Therapy, and Smoking Cessation
      Counseling Reimbursement Q & A's.

PMID- 28520598
TI  - Imaging plus X: multimodal models of neurodegenerative disease.
AB  - PURPOSE OF REVIEW: This article argues that the time is approaching for data
      driven disease modelling to take centre stage in the study and management of
      neurodegenerative disease. The snowstorm of data now available to the clinician
      defies qualitative evaluation; the heterogeneity of data types complicates
      integration through traditional statistical methods; and the large datasets
      becoming available remain far from the big-data sizes necessary for fully data
      driven machine-learning approaches. The recent emergence of data-driven disease
      progression models provides a balance between imposed knowledge of disease
      features and patterns learned from data. The resulting models are both predictive
      of disease progression in individual patients and informative in terms of
      revealing underlying biological patterns. RECENT FINDINGS: Largely inspired by
      observational models, data-driven disease progression models have emerged in the
      last few years as a feasible means for understanding the development of
      neurodegenerative diseases. These models have revealed insights into
      frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's
      disease and other conditions. For example, event-based models have revealed finer
      graded understanding of progression patterns; self-modelling regression and
      differential equation models have provided data-driven biomarker trajectories;
      spatiotemporal models have shown that brain shape changes, for example of the
      hippocampus, can occur before detectable neurodegeneration; and network models
      have provided some support for prion-like mechanistic hypotheses of disease
      propagation. The most mature results are in sporadic Alzheimer's disease, in
      large part because of the availability of the Alzheimer's disease neuroimaging
      initiative dataset. Results generally support the prevailing amyloid-led
      hypothetical model of Alzheimer's disease, while revealing finer detail and
      insight into disease progression. SUMMARY: The emerging field of disease
      progression modelling provides a natural mechanism to integrate different kinds
      of information, for example from imaging, serum and cerebrospinal fluid markers
      and cognitive tests, to obtain new insights into progressive diseases. Such
      insights include fine-grained longitudinal patterns of neurodegeneration, from
      early stages, and the heterogeneity of these trajectories over the population.
      More pragmatically, such models enable finer precision in patient staging and
      stratification, prediction of progression rates and earlier and better
      identification of at-risk individuals. We argue that this will make disease
      progression modelling invaluable for recruitment and end-points in future
      clinical trials, potentially ameliorating the high failure rate in trials of,
      e.g., Alzheimer's disease therapies. We review the state of the art in these
      techniques and discuss the future steps required to translate the ideas to front
      line application.

PMID- 28520603
TI  - Does Negative-Pressure Wound Therapy for the Open Abdomen Benefit the Patient? A
      Retrospective Cohort Study.
AB  - OBJECTIVE: Negative-pressure wound therapy (NPWT) is the most modern and
      sophisticated method of temporary abdominal closure. The aim of the study was to
      determine the significant predictors for mortality in patients with NPWT.
      SETTING: University Clinical Centre Maribor, Slovenia MATERIALS AND METHODS:: The
      authors performed a retrospective cohort study of all patients treated with NPWT
      between January 1, 2011, and December 31, 2014. RESULTS: In the univariate
      analysis, the type of wound closure, more than 7 NPWT changes, the total days
      with NPWT, and time to wound closure were significantly associated with death of
      the patient. In the multivariate analysis, only the number of more than 7 NPWT
      changes was found as a significant predictor for death (P = .038). CONCLUSIONS:
      Negative-pressure wound therapy is a method of choice for the treatment of open
      abdomen if there is a clear indication. However, clinicians should try all
      measures to remove the NPWT system and close the abdomen as soon as possible
      because prolonged use is associated with significantly higher mortality.

PMID- 28520604
TI  - In Vitro Evaluation of Betafoam, a New Polyurethane Foam Dressing.
AB  - BACKGROUND: A new polyurethane foam dressing impregnated with 3% povidone-iodine
      (Betafoam; Genewell, Seoul, Korea) was recently developed based on the hypothesis
      that its physical properties, including improved moisture-retention capacity and
      antimicrobial activity, are at least as good as those achieved with the current
      foam dressings that contain silver, but also associated with reduced cost and
      cytotoxicity to host cells. The purpose of this in vitro study was to evaluate
      the efficacy of Betafoam by comparing its physical properties, antimicrobial
      activity, and cytotoxicity with those of 3 silver foam dressings (Allevyn-Ag
      [Smith & Nephew, Hull, United Kingdom]; Mepilex-Ag [Molnlycke Health Care,
      Gothenburg, Sweden]; and PolyMem-Ag [Ferris MFG Corp, Burr Ridge, Illinois]) used
      worldwide. METHODS: This study measured each dressing's pore size, fluid
      absorption time, fluid absorption capacity, fluid retention capacity,
      antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa,
      and cytotoxicity to mouse fibroblasts. RESULTS: Betafoam had the smallest pore
      size, the fastest fluid absorption time, greatest fluid absorption, and best
      retention capacities among the tested foam dressings. Antimicrobial activity was
      not significantly different among the dressings. However, Betafoam also
      demonstrated the lowest cytotoxicity to the fibroblasts. CONCLUSIONS: Betafoam
      may result not only in desirable rapid regulation of exudation but also
      antimicrobial activity with minimal cytotoxicity to host cells that are key
      requirements for wound healing.

PMID- 28520605
TI  - Reducing Postsurgical Wound Complications: A Critical Review.
AB  - GENERAL PURPOSE: To provide information on risk factors for surgical site
      infections (SSIs) and actions to mitigate that risk. TARGET AUDIENCE: This
      continuing education activity is intended for surgeons, surgical teams,
      physicians, physician assistants, nurse practitioners, and nurses with an
      interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After
      participating in this educational activity, the participant should be better able
      to:1. Identify modifiable risk factors associated with the development of SSIs.2.
      Select steps to mitigate the risks for and morbidity from SSIs. ABSTRACT: Given
      the current reimbursement structure, the avoidance of a surgical site infection
      (SSI) is crucial. Although many risk factors are associated with the formation of
      an SSI, a proactive and interprofessional approach can help modify some factors.
      Postoperative strategies also can be applied to help prevent an SSI. If an SSI
      becomes a chronic wound, there are recommended guidelines and strategies that can
      foster healing.

PMID- 28520606
TI  - Quality Payment Program: Advancing Care Information Performance Category: Part 2.

PMID- 28520607
TI  - Reducing Postsurgical Wound Complications: A Critical Review.

PMID- 28520608
TI  - Choroideremia.
AB  - PURPOSE OF REVIEW: Although much has been written to define the phenotype and
      genotype of choroideremia (CHM), research continues to provide new insights that
      serve to better understand its pathogenesis and the directions for potential
      experimental therapies. RECENT FINDINGS: We would like to highlight new findings,
      expanding the type of disease-causing mutations to include mutations in the CHM
      promoter that will dramatically influence gene expression. Information derived
      from careful phenotyping of patients points increasingly to the central role of
      the retinal pigment epithelium as the key cell layer affected in the degenerative
      process. Finally, we will review the current initiatives that are testing vector
      mediated gene replacement approaches in humans, including our current
      understanding of the likelihood of success by this approach. SUMMARY: Clinical
      and basic vision science have benefited greatly by the active engagement of
      patients with CHM in clinical research studies. The impetus for their involvement
      in these studies has been generated by the initial results of safety from
      subretinal injection of and AAV2.REP1 vector in humans. Follow-up studies in the
      next few years are expected to show if this approach will modify disease
      progression.

PMID- 28520609
TI  - Fuchs Endothelial Corneal Dystrophy in a Child.

PMID- 28520610
TI  - Candidates for inclusion in a universal antiretroviral regimen: dolutegravir.
AB  - PURPOSE OF REVIEW: The review addresses the role of dolutegravir (DTG) in first
      line therapy. In the era of test and treat, where United Nations AIDS Program and
      WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated,
      and simple therapeutic options are needed. RECENT FINDINGS: DTG has been tested
      in large clinical trials in treatment-naive patients, showing noninferiority to
      raltegravir and superiority compared with efavirenz and ritonavir-boosted
      darunavir, respectively. The main features of DTG are reviewed in this study,
      including efficacy, safety, high-resistance barrier, daily treatment schedule,
      and coformulation as single-tablet regimen. Use of DTG in special populations is
      also reviewed. Tolerability, with focus in neuropsychiatric disturbances is
      discussed in particular. DTG has shown high efficacy level, tested in males and
      females, has no limitations in patients with renal and/or hepatic impairment and
      is available as single drug (to be combined with two nucleoside reverse
      transcriptase inhibitors in fixed combinations) or as a single-tablet regimen
      combined with abacavir and lamivudine. SUMMARY: DTG is an excellent candidate for
      initial therapy in HIV-infected patients. If safety of DTG in pregnant women are
      confirmed by ongoing studies, DTG might become the first option in WHO
      antiretroviral guidelines.

PMID- 28520612
TI  - Guidelines on the management of arterial hypertension and related comorbidities
      in Latin America.

PMID- 28520611
TI  - Treatment Outcomes of Third-line Antiretroviral Regimens in HIV-infected Thai
      Adolescents.
AB  - BACKGROUND: Efficacy and safety data of third-line antiretroviral (ARV) regimens
      in adolescents are limited. METHODOLOGY: This study enrolled HIV-infected Thais
      who were treated with third-line regimens consisting of darunavir/ritonavir
      (DRV/r), etravirine (ETR), tipranavir/ritonavir or raltegravir. RESULTS: Fifty
      four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48
      weeks. Reasons for switch were second-line failure (n = 44) and toxicity to
      second-line regimens (n = 10). At switching to third-line ARV, the median age
      (interquartile range) was 14.3 (12.4-15.4) years. Genotypes at time of second
      line failure (n = 44) were M184V (77%), >=4 thymidine analogue mutations (25%),
      non-nucleoside reverse transcriptase inhibitor-resistant associated mutation
      (RAM) (80%), ETR-RAM score >=4 (14%), any lopinavir-RAM (59%) and >=1 major DRV
      RAM (41%). The third-line regimens had a median of 4 (min-max, 4-6) drugs and
      included ETR/DRV/r (43%), DRV/r (33%), ETR (17%), tipranavir/ritonavir (2%) or
      raltegravir/DRV/r/ (4%). The median CD4 (interquartile range) increased from 16%
      (12-21) at third-line switch to 21% (18-25) and 410 (172-682) to 607 (428-742)
      cells/mm at 48 weeks (P < 0.001). HIV RNA declined from 3.9 (2.9-4.9) to 1.6 (1.6
      3.0) log10 copies/mL (P < 0.001) and 33/50 (66%) had levels <50 copies/mL at 48
      weeks. Seventeen (31%) had HIV-RNA >=1000 copies/mL; about half due to poor
      adherence; genotyping in 13 of these adolescents revealed ETR-RAM score >=4 in 2
      (15%) and >=1 major DRV-RAM in 7 (54%). CONCLUSIONS: Third-line ARV therapy was
      well tolerated and resulted in virologic suppression in 70% of adolescents at 1
      year. Poor adherence and limited ARV options are major problems in the long-term
      management of adolescents with HIV.

PMID- 28520613
TI  - Uric acid and blood pressure: exploring the role of uric acid production in The
      Maastricht Study.
AB  - OBJECTIVE: Accumulation of reactive oxygen species by increased uric acid
      production has been suggested as a possible underlying mechanism for the
      association between uric acid and high blood pressure (BP). We, therefore,
      investigated the association between serum uric acid concentration and 24-h
      urinary uric acid excretion, as proxy for uric acid production, with ambulatory
      24-h blood pressure and hypertension. METHODS: Cross-sectional analyses were
      conducted among 2555 individuals [52% men, mean age 60.0 +/- 8.2 years; 27% type
      2 diabetes (by design)] from The Maastricht Study. Multivariable regression
      analyses were performed to investigate the association of serum uric acid and 24
      h urinary uric acid excretion with 24-h pulse pressure, 24-h mean arterial
      pressure (MAP), and hypertension. RESULTS: After adjustment for traditional
      hypertension risk factors, serum uric acid concentration (per SD of 81 MUmol/l)
      was associated with higher 24-h MAP [beta 0.63 mmHg; confidence interval (CI)
      0.27-1.00] and positively associated with hypertension (odds ratio 1.43; CI 1.27
      1.61). Urinary uric acid excretion (per SD of 140 mg/day/1.73 m) was associated
      with higher 24-h MAP (beta 0.79 mmHg; CI 0.46-1.12) and with hypertension (odds
      ratio 1.13; CI 1.02-1.25). There was no significant association between serum and
      24-h urinary uric acid excretion with 24-h pulse pressure. There was no
      interaction with sex or age for the aforementioned associations. CONCLUSION:
      Higher serum and urinary uric acid concentrations were associated with higher 24
      h MAP and hypertension. These results suggest that serum and 24-urinary uric acid
      concentrations, the latter as proxy for uric acid production are, independent of
      each other, associated with BP and hypertension.

PMID- 28520614
TI  - Incidence of Neurological Disorders Among HIV-Infected Individuals With Universal
      Health Care in Taiwan From 2000 to 2010.
AB  - OBJECTIVE: To determine the incidence of and factors associated with neurological
      disorders in a large Taiwanese cohort of HIV-infected persons with free access to
      highly active antiretroviral therapy (HAART). DESIGN: A retrospective population
      based cohort study was conducted using the National Health Insurance Research
      Database for the years 2000-2010. METHODS: We identified 13,316 HIV-positive
      persons from 2000 through 2010. We used direct standardization to calculate age
      adjusted and sex-adjusted incidence rates based on the 2000 World Health
      Organization world standard population. Factors associated with neurological
      disorders were analyzed using a Cox proportional hazards model. RESULTS: The
      standardized incidence of neurological disorders among HIV-infected persons
      increased from 22.16 per 1000 person-years in 2000 to 25.23 per 1000 person-years
      in 2010. Cognitive disorders increased significantly from 0.36 per 1000 person
      years in 2001 to 7.44 per 1000 person-years in 2010 (trend P < 0.001). The rate
      of neurological disorders increased with age >=55 years [adjusted hazard ratios
      (AHRs) 2.54, 95% confidence interval (CI): 1.89 to 3.40], hypertension (AHR 1.41,
      95% CI: 1.12 to 1.76), substance abuse (AHR 1.65, 95% CI: 1.36 to 2.02),
      opportunistic infection (AHR 1.76, 95% CI: 1.47 to 2.11), syphilis (AHR 1.27, 95%
      CI: 1.10 to 1.47), and emergency department visits >5 (AHR 2.41, 95% CI: 1.96 to
      2.97). The incidence of neurological disorders was negatively associated with
      adherence to HAART (adherence >=85% AHR: 0.79, 95% CI: 0.64 to 0.97).
      CONCLUSIONS: The rising incidence of cognitive disorders among HIV-positive
      persons highlights the need to provide routine neurological evaluations at
      clinical visits. Receiving HAART with adherence >=85% contributes to a reduced
      risk of neurological disorders.

PMID- 28520617
TI  - Statin Prescribing Practices in the Comprehensive Care for HIV-Infected Patients.

PMID- 28520616
TI  - Brief Report: Pediatric Cancer Burden and Treatment Resources Within the
      Pediatric IeDEA Consortium.
AB  - INTRODUCTION: The incidence and treatment of cancer in HIV-infected children from
      resource-limited settings has not been extensively studied. OBJECTIVES: Develop
      and implement a cross-sectional survey to evaluate pediatric cancer burden,
      diagnostic modalities in use, and treatment availability as perceived by HIV
      clinic staff at regional International Epidemiology Databases to Evaluate AIDS
      (IeDEA) sites. METHODS: IeDEA regional investigators developed a cross-sectional
      clinical site survey which included questions on the numbers and types of
      pediatric cancers observed, modalities used to treat identified cancers, and
      treatment options available at individual sites in the Asia-Pacific, Latin
      America, Central Africa, East Africa, West Africa, and Southern Africa regions.
      RESULTS: Kaposi sarcoma, non-Hodgkin lymphoma, and Burkitt lymphoma were reported
      by site personnel to be the most prevalent types of cancer in the pediatric HIV
      population. Survey results indicate that access to comprehensive cancer treatment
      modalities is very limited for children in these regions despite HIV care and
      treatment sites reporting that they diagnose pediatric cancers. Responses also
      showed that evaluating cancer in the pediatric HIV population is a challenge due
      to a lack of resources and varying treatment availability within regions.
      CONCLUSIONS: Further study is needed to increase our understanding of the
      changing epidemiology of cancer in HIV-infected pediatric populations. Increased
      financial and technical resources are critical to aid in the advancement of
      health services to support treatment of these children in resource-constrained
      settings.

PMID- 28520618
TI  - Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological
      Failure Among Adolescents Failing Second-Line Antiretroviral Treatment.
AB  - BACKGROUND: Adequate antiretroviral exposure is crucial to virological
      suppression. We assessed the relationship between atazanavir hair levels with
      self-reported adherence, virological outcomes, and the effect of a home-based
      adherence intervention in HIV-infected adolescents failing second-line
      antiretroviral treatment in Zimbabwe. METHODS: HIV-infected adolescents on
      atazanavir/ritonavir-based second-line treatment for >=6 months with viral load
      (VL) >1000 copies/mL were randomized to either standard care (control) or
      standard care plus modified directly administered antiretroviral therapy
      (intervention). Questionnaires were administered; VL and hair samples were
      collected at baseline and after 90 days in each group. Viral suppression was
      defined as <1000 copies/mL after follow-up. RESULTS: Fifty adolescents (10-18
      years) were enrolled; 23 (46%) were randomized to intervention and 27 (54%) to
      control. Atazanavir hair concentration <2.35 ng/mg (lower interquartile range for
      those with virological suppression) defined a cutoff below which most
      participants experienced virological failure. Male sex (P = 0.03), virological
      suppression at follow-up (P = 0.013), greater reduction in VL (P = 0.006), and
      change in average self-reported adherence over the previous month (P = 0.031)
      were associated with adequate (>2.35 ng/mg) hair concentrations. Participants
      with virological failure were more likely to have suboptimal atazanavir hair
      concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences
      in atazanavir hair concentration between the arms after follow-up. CONCLUSIONS: A
      threshold of atazanavir concentrations in hair (2.35 ng/mg), above which
      virological suppression was likely, was defined for adolescents failing second
      line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self
      reported adherence were associated with adequate atazanavir hair concentrations.
      Antiretroviral hair concentrations may serve as a useful clinical tool among
      adolescents.

PMID- 28520619
TI  - Brief Report: Late Efavirenz-Induced Ataxia and Encephalopathy: A Case Series.
AB  - BACKGROUND: WHO treatment guidelines recommend efavirenz in first-line
      antiretroviral therapy (ART). Efavirenz commonly causes early transient
      neuropsychiatric adverse events. We present 20 cases with severe encephalopathy
      accompanied by ataxia due to efavirenz toxicity. METHODS: Consecutive HIV
      infected adults taking efavirenz-containing ART admitted to Tshepong hospital,
      Klerksdorp, South Africa with ataxia and encephalopathy were included in this
      case series. RESULTS: We identified 20 women admitted to hospital with severe
      ataxia. All received efavirenz-based ART for a median of 2 years. All had severe
      ataxia and none had nystagmus. Eleven had features of encephalopathy. Median
      weight was 34 kg [interquartile range (IQR): 29.7-35.3]; median CD4 count 299
      cells/mm (IQR: 258-300) and most (18 of 19) were virally suppressed. Eight
      patients had a record of prior weights and 7 of 8 showed significant weight loss
      with a median weight loss of 10.8 kg (IQR: 8-11.6). All cases had plasma
      efavirenz assays, 19 were supratherapeutic (more than twice the upper level of
      therapeutic range), and 15 had concentrations above the upper limit of assay
      detection. Ataxia resolved after withdrawal of efavirenz at a median time of 2
      months (IQR: 1.25-4) and recurred in 2 of 3 patients when rechallenged.
      Admissions before diagnosis were frequent with 10 cases admitted previously.
      Three women died. CONCLUSIONS: Efavirenz toxicity may present with severe
      reversible ataxia often with encephalopathy years after its initiation, likely in
      genetic slow metabolizers. We recommend that patients whose weight is <40 kg
      receive lower doses of efavirenz and that therapeutic drug monitoring be
      considered, and efavirenz stopped in patients presenting with ataxia. Eight
      patients had a record of prior subsequent weights and 7 of 8 showed significant
      weight loss gain; median gain of 10.8 kg (IQR: 8-11.6).

PMID- 28520620
TI  - (-)-Epigallocatechin-3-gallate ameliorates memory impairment and rescues the
      abnormal synaptic protein levels in the frontal cortex and hippocampus in a mouse
      model of Alzheimer's disease.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic extract
      in green tea and it has attracted increasing attention for its multiple bioactive
      effects. However, the mechanisms by which EGCG exerts its neuroprotective actions
      in Alzheimer's disease (AD) are presently lacking. In the present study, a
      sporadic AD transgenic mouse model known as senescence-accelerated mouse prone 8
      (SAMP8) was used to investigate whether oral administration of EGCG could improve
      recognition and memory function through reduction of amyloid beta (Abeta) and tau
      hyperphosphorylation. We also investigated the effects of chronic EGCG treatment
      on the synaptic dysfunction in the frontal cortex (FC) and the hippocampus (Hip)
      of AD mice. The results showed that long-term oral consumption of EGCG at a
      relatively high dose (15 mg/kg) improved memory function in SAMP8 mice in the Y
      maze and Morris water maze. The levels of Abeta1-42 and BACE-1 in FC and Hip were
      significantly reduced by EGCG treatment. EGCG treatment also prevented the
      hyperphosphorylation of tau and reversed the decreased synaptic protein marker
      synaptophysin and postsynaptic density protein 95 in FC and Hip of SAMP8 mice.
      The present study suggests that long-term oral consumption of EGCG ameliorates
      impairments in spatial learning and memory and rescues the reduction in synaptic
      proteins observed in an AD mouse model. Thus, EGCG may represent a novel
      candidate agent for the treatment of neurodegenerative diseases.

PMID- 28520622
TI  - Perilesional Reorganization in a Patient With Brain Tumor.

PMID- 28520615
TI  - Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North
      America Compared With the General Population.
AB  - BACKGROUND: Previous studies of cardiovascular disease (CVD) among HIV-infected
      individuals have been limited by the inability to validate and differentiate
      atherosclerotic type 1 myocardial infarctions (T1MIs) from other events. We
      sought to define the incidence of T1MIs and risk attributable to traditional and
      HIV-specific factors among participants in the North American AIDS Cohort
      Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence
      rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC)
      cohort. METHODS: We ascertained and adjudicated incident MIs among individuals
      enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs,
      adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk
      factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA
      ACCORD with those from ARIC. RESULTS: Among 29,169 HIV-infected individuals, the
      IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was
      significantly higher compared with participants in ARIC [1.30 (1.09 to 1.56)]. In
      multivariable analysis restricted to HIV-infected individuals and including
      traditional CVD risk factors, the rate of T1MI increased with decreasing CD4
      count [>=500 cells/MUL: ref; 350-499 cells/MUL: aIRR = 1.32 (0.98 to 1.77); 200
      349 cells/MUL: aIRR = 1.37 (1.01 to 1.86); 100-199 cells/MUL: aIRR = 1.60 (1.09
      to 2.34); <100 cells/MUL: aIRR = 2.19 (1.44 to 3.33)]. Risk associated with
      detectable HIV RNA [<400 copies/mL: ref; >=400 copies/mL: aIRR = 1.36 (1.06 to
      1.75)] was significantly increased only when CD4 was excluded. CONCLUSIONS: The
      higher incidence of T1MI in HIV-infected individuals and increased risk
      associated with lower CD4 count and detectable HIV RNA suggest that early
      suppressive antiretroviral treatment and aggressive management of traditional CVD
      risk factors are necessary to maximally reduce MI risk.

PMID- 28520621
TI  - Outbreaks in the adult ICUs.
AB  - PURPOSE OF REVIEW: Infectious disease outbreaks in the critical care setting are
      common and serious consequence. This article reviews and summarizes recent
      outbreaks in the adult ICUs. RECENT FINDINGS: Outbreaks of multidrug-resistant
      bacteria, fungi, and emerging viruses in ICUs from different countries are
      common. Outbreak investigation relies on epidemiologic methods, microbiologic
      studies, and molecular typing methods. Overuse of antibiotics, gaps in
      implementing infection prevention measures, and contaminated environment are
      common causes of ICU outbreaks. ICU staff awareness of and preparedness for such
      outbreaks are crucial for outbreak prevention and control. Specific infection
      control measures vary according to outbreak transmission mode and cause. SUMMARY:
      Outbreaks remain a significant threat to healthcare systems. Proper
      implementation of infection prevention practices and judicious use of antibiotics
      are needed for outbreak prevention in adult ICUs. Surveillance, proper outbreak
      investigation, adherence to infection prevention and control measures, and
      thorough disinfection of contaminated areas are required to successfully manage
      outbreaks.

PMID- 28520623
TI  - Subcrestal Iliac-Screw: A Technical Note Describing a Free Hand, In-line, Low
      Profile Iliac Screw Insertion Technique to Avoid Side-connector Use and Reduce
      Implant Complications.
AB  - STUDY DESIGN: Case-series. OBJECTIVE: To report our modified iliac-screw
      insertion technique and its clinical outcomes. SUMMARY OF BACKGROUND DATA: Iliac
      screws are one of the preferred methods for modern spinopelvic-fixation. However,
      the technique is not without complications, predominantly because of iliac-screw
      head prominence, leading to pain and revisions. Conventional iliac-screw entry
      point is sited superficially at the posterior-superior-iliac-spine (PSIS)
      contributing to screw-head prominence. We propose a more low-profile, subcrestal
      entry point that is more medial and inferior to the PSIS at the medial wall of
      the iliac crest, lying underneath the crest but above the sacroiliac joint. This
      position keeps the screw-head low profile and in-line with proximal
      instrumentation to ease rod engagement. METHODS: Ten consecutive patients who
      underwent spinal deformity correction surgery using the modified iliac-screw
      entry point fixations were enrolled. Clinical, radiological, and surgical
      parameters were reviewed. RESULTS: Five males and five females with average age
      of 66 years and average follow up of 29 months were reviewed. Mean preoperative
      Cobb angle and C7-SVA were 32.1 degrees  and 10.3 cm, respectively. Surgical
      indication was progressive deformity and neurogenic claudication in eight cases
      and fracture in two cases. Twenty noncannulated, polyaxial iliac-screws with
      median dimension of 7.5 x 75 mm were inserted free hand. Bilateral S1 screws were
      used in all except two cases. Only five out of 16 iliac-screws with concomitant
      S1 screws needed side-connectors. At the last follow up only one iliac-screw head
      was felt to be prominent but without pain in a Parkinson's patient. None of the
      10 patients had cases of revision, breakages, or sacroiliac pain. CONCLUSION:
      Subcrestal iliac-screw insertion is feasible, safe, and has the potential to
      reduce screw-head complications and avoid the use of side-connectors, lowering
      construct complexity and cost. The technique has the advantage of both the low
      profile S2 alar iliac screw and the ease of free-hand insertion of the
      traditional iliac-screw. LEVEL OF EVIDENCE: 4.

PMID- 28520624
TI  - Cardiac Rehabilitation Outcomes by Ethnocultural Background: RESULTS FROM THE
      CANADIAN CARDIAC REHAB REGISTRY.
AB  - BACKGROUND: Patients of diverse ethnocultural backgrounds are underrepresented
      among participants and, hence, little is known about their outcomes. The
      objectives of this study were to compare cardiac rehabilitation (CR) utilization,
      cardiovascular risk factor reduction (blood pressure, lipids, anthropometrics),
      and functional capacity between white and ethnocultural minority patients
      participating in CR across Canada. METHODS: The study was a retrospective,
      observational cohort study using the Canadian Cardiac Rehab Registry (CCRR).
      Participants from an ethnocultural minority (n >= 25) were propensity-matched to
      white participants based on sociodemographic and clinical characteristics. CR
      outcomes were compared. RESULTS: In the CCRR, 3848 (53.8%) participants had an
      ethnocultural background reported. Of those, whites (n = 3630) and South Asians
      (n = 26), Southeast Asians (n = 45), and Arab/West Asians (n = 37) minorities had
      sufficient representation in the registry to be analyzed. In the matched sample,
      364 (97.1%) participants completed a discharge assessment. Southeast Asian
      participants adhered to (96.5%, P = .02) and completed (88.2%, P = .02) CR more
      often than white participants (90.2% and 55.6%, respectively). Southeast Asian
      participants had significantly lower diastolic blood pressure (P = .002) at CR
      discharge than matched white participants. No other differences in outcomes or
      functional capacity were observed. CONCLUSIONS: Ethnocultural minorities make up
      a small proportion of CR participants in Canada. However, when they do
      participate, they achieve similar CR outcomes compared with white participants.
      CR programs should seek to ensure ethnoculturally diverse patients are referred
      to their programs and ensure their programs are culturally sensitive to the needs
      of the preponderant ethnocultural groups in their catchment areas.

PMID- 28520626
TI  - MULTIMODAL IMAGING OF ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY WITH
      OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ADAPTIVE OPTICS SCANNING LASER
      OPHTHALMOSCOPY.
AB  - PURPOSE: To report a case of acute exudative polymorphous vitelliform maculopathy
      including the findings of optical coherence tomography angiography and adaptive
      optics scanning laser ophthalmoscopy. METHODS: Findings on clinical examination,
      color fundus photography, spectral-domain optical coherence tomography, infrared
      reflectance, autofluorescence, optical coherence tomography angiography, and
      adaptive optics scanning laser ophthalmoscopy. RESULTS: A 54-year-old white man
      with no significant medical history and history of smoking presented with
      bilateral multiple serous and vitelliform detachments consistent with acute
      exudative polymorphous vitelliform maculopathy. Extensive infectious,
      inflammatory, and malignancy workup was negative. Spectral-domain optical
      coherence tomography showed thickened, hyperreflective ellipsoid zone, subretinal
      fluid, and focal as well as diffuse subretinal hyperreflective material
      corresponding to the vitelliform lesions. Optical coherence tomography
      angiography showed normal retinal and choroidal vasculature, whereas adaptive
      optics scanning laser ophthalmoscopy showed circular focal "target" lesions at
      the level of the photoreceptors in the area of foveal detachment. CONCLUSION:
      Multimodal imaging is valuable in evaluating patients with acute exudative
      polymorphous vitelliform maculopathy.

PMID- 28520625
TI  - The Relationship Between Weather and Objectively Measured Physical Activity Among
      Individuals With COPD.
AB  - PURPOSE: Although daily variation in weather impacts physical activity (PA)
      levels among relatively healthy individuals, it is largely unknown whether this
      relationship occurs for those living with chronic obstructive pulmonary disease
      (COPD). The purpose of this study was to examine how daily variation in
      temperature, rain, and snow is related to objectively measured PA among patients
      with COPD, and whether demographic or clinical characteristics moderate these
      relationships. METHODS: Patients with COPD completed a questionnaire and wore a
      pedometer for 7 days at baseline, end of pulmonary rehabilitation (PR), and 3 and
      9 months after completing PR (28 days in total). RESULTS: Hierarchal linear
      modeling showed that daily mean temperature and total daily rainfall, but not
      snowfall, independently predicted steps/day, controlling for demographic and
      clinical covariates in 189 patients in PR. Specifically, an increase of 10
      degrees C translates into 316 more steps (6.6% of mean steps/day) whereas a
      rainfall of 10 mm translates to 175 less steps (3.6% of mean steps/day).
      Furthermore, those with higher income had more steps/day on warmer days.
      CONCLUSIONS: These results add to converging evidence that weather plays an
      important role in determining PA among individuals with COPD.

PMID- 28520627
TI  - POSTERIOR SCLERAL MELANOCYTOSIS: A NOVEL FUNDUS FINDING MASQUERADING AS A
      CHOROIDAL NEVUS.
AB  - PURPOSE: To report a case of "posterior scleral melanocytosis," a pigmented
      lesion of the posterior sclera that clinically resembles a flat choroidal nevus.
      METHODS: Case report of a patient with posterior scleral melanocytosis.
      Multimodal imaging, including swept source optical coherence tomography, was used
      to demonstrate the scleral location of the pigmented lesion and to distinguish
      its features from a typical choroidal nevus present in the same eye. RESULTS: An
      86-year-old woman was seen for regular follow-up for neovascular age-related
      macular degeneration in her right eye and 2 pigmented lesions in her left eye,
      both presumed to be choroidal nevi. Anterior segment examination showed no
      evidence of ocular or dermal melanocytosis. Optical coherence tomography of the
      pigmented lesion in the left eye showed two distinct patterns. One lesion showed
      hyperreflectivity within the choroidal tissue associated with posterior
      shadowing, whereas the second lesion showed normal choroidal reflectivity with
      hyperreflectivity confined to the inner sclera associated with marked posterior
      shadowing. CONCLUSION: To the authors' knowledge, this is the first report of
      posterior scleral melanocytosis, a pigmented fundus lesion confined to the inner
      sclera. The need for high-penetrance optical coherence tomography to
      differentiate these lesions from a typical choroidal nevus may explain why this
      entity has not been previously described. The true nature of this entity will
      ultimately require histopathologic study.

PMID- 28520628
TI  - Impact of Perioperative Blood Transfusion on Survival Among Women With Breast
      Cancer.

PMID- 28520629
TI  - Blepharoplasty Effect on a Described Algorithmic Approach to External Ptosis
      Repair: Is It Time for Unbundling?
AB  - PURPOSE: To investigate the effects of performing a previously described
      algorithmic levator resection for involutional ptosis with a blepharoplasty
      instead of through a small incision. METHODS: Eyelids with involutional ptosis
      and normal levator function were included in the study. An upper blepharoplasty
      was performed first. An external levator resection was then performed based on a
      described technique involving 2 mm resection of aponeurosis for 1 mm of desired
      lift, consistent tension on the aponeurosis between surgical cases, and
      standardized suture placement. RESULTS: Forty-one eyelids of 25 patients were
      included. Mean postoperative margin to reflex distance 1 (MRD1) was 2.98 mm,
      which was significantly higher than preoperative MRD1 (0.67 mm), but lower than
      the predetermined goal MRD1 (3.35 mm). Eight eyelids did not meet primary outcome
      of MRD1 within 1 mm of goal MRD1, with 5 undercorrections. There was no
      difference between the postoperative MRD1 compared with the same ptosis technique
      performed through a small incision only, but there were more intraoperative
      suture adjustments and fewer eyelids meeting the primary outcome when a
      concurrent blepharoplasty was performed. CONCLUSIONS: The addition of
      blepharoplasty with a previously described algorithmic approach external levator
      resection has an 80% success rate in achieving the primary outcome. When compared
      with a small-incision ptosis repair, concurrent blepharoplasty results in a less
      predictable outcome and an increased need for intraoperative adjustment.
      Performing an algorithmic technique for external levator resection with a
      blepharoplasty has less predictable outcomes, which raises the question of
      separating the procedures to improve patient care.

PMID- 28520630
TI  - Diagnostic Yield of Routine Electroencephalography With Concurrent Video
      Recording in Detecting Interictal Epileptiform Discharges in Relation to Reasons
      for Request: A Prospective Study of 1,080 Video-Electroencephalograms.
AB  - PURPOSE: The aim of this study was to prospectively analyze the sensitivity and
      specificity of routine electroencephalography with concurrent video recording
      (vEEG) in relation to the reasons for requesting the test and to investigate when
      routine vEEG should be requested. METHODS: We prospectively analyzed 1,080
      consecutive vEEGs performed between April 2015 and April 2016. The requests for
      vEEG were classified as requests with a low suspicion of epilepsy (syncope,
      confusion or delirium, suspicion of psychogenic nonepileptic seizures, and
      paroxysmal focal neurological deficit) or requests with a high suspicion of
      epilepsy (first clinical seizure, suspected status epilepticus, follow-up study
      of a patient with epilepsy, and acute symptomatic seizures). Predominant vEEG
      findings (ictal and interictal epileptiform activities, diffuse, or focal slowing
      and triphasic waves) were analyzed, and sensitivity and specificity [ZERO WIDTH
      SPACE][ZERO WIDTH SPACE]values calculated. RESULTS: The most common indication
      for vEEG was a follow-up study of patients with epilepsy (38%), followed by first
      clinical seizure (19.3%) and suspected status epilepticus (11%). The respective
      specificity and sensitivity values were 93% and 58% for 235 vEEGs performed in
      children/adolescents (<=18 years), 95% and 40% for 533 vEEGs performed in adults
      (>18 <= 65 years), and 93% and 39% for 312 vEEGs performed in older adults (>65
      years). Twenty-four patients with false-positive paroxysms had a clinical
      diagnosis of confusional state or paroxysmal focal neurological deficit.
      Neurologists and neuropediatricians with experience in managing epilepsy had
      higher specificity values than general neurologists or physicians (P = 0.012).
      CONCLUSIONS: In our series, vEEG abnormalities were mainly observed in patients
      with clinical findings highly suggestive of epilepsy. In confusional states, and
      paroxysmal focal neurological deficit vEEG could be indicated.

PMID- 28520631
TI  - Operculo-Insular Epilepsy: Scalp and Intracranial Electroencephalographic
      Findings.
AB  - PURPOSE: Operculo-insular seizures are heterogeneous and may resemble seizures
      originating from the temporal, frontal, or parietal lobe. Although surface and
      invasive EEG recordings are often necessary to detect operculo-insular seizures,
      electrophysiological features of operculo-insular epilepsies remain poorly
      characterized. This study describes the EEG findings of patients with operculo
      insular epilepsy. METHODS: We reviewed electrophysiological data of all patients
      (n = 9) with operculo-insular seizures revealed by intracranial EEG and for whom
      operculo-insular epilepsy was confirmed by good seizure outcome after resective
      or radiosurgery at our center between 2005 and 2013. Patients were divided
      according to whether their seizure focus involved the anterior (group 1; n = 4)
      or posterior (group 2; n = 5) portion of the insula. RESULTS: Interictal scalp
      EEG was lateralizing and showed distinct topographical spike patterns between
      groups: frontal and temporal in group 1, temporal in group 2. Intracranial
      recordings showed abundant spikes limited to the operculo-insular region or
      involving distant areas in the frontal/temporal (group 1) and temporal/parietal
      lobes (group 2). Ictal intracranial EEG revealed discharges limited to the insula
      or simultaneously involving extrainsular contacts at onset, notably the
      orbitofrontal cortex (group 1) and the frontal and parietal opercula (group 2),
      and propagating to the frontal and temporal lobes in group 1 and to parietal and
      temporal lobes in group 2. CONCLUSIONS: Spike distribution and seizure
      propagation in operculo-insular epilepsy follows an anterior-to-posterior pattern
      mirroring an anterior or posterior insular focus localization. When presented
      with frontal and/or temporal epileptiform abnormalities, an operculo-insular
      focus should be considered.

PMID- 28520632
TI  - Disruption of Brain-Heart Coupling in Sepsis.
AB  - PURPOSE: To investigate heart rate and EEG variability and their coupling in
      patients with sepsis and determine their relationship to sepsis severity and
      severity of sepsis-associated brain dysfunction. METHODS: Fifty-two patients with
      sepsis were prospectively identified, categorized as comatose (N = 30) and
      noncomatose (N = 22), and compared with 11 control subjects. In a 30-minute EEG
      and electrocardiogram recording, heart rate variability and EEG variability
      (measured by the variability of relative power in a modified alpha band = RAP)
      and their coupled oscillations were quantified using linear (least-square
      periodogram and magnitude square coherence) and nonlinear (Shannon entropy and
      mutual information) measures. These measures were compared between the three
      groups and correlated with outcome, adjusting for severity of sepsis. RESULTS:
      Several measures of heart rate variability and EEG variability and of their
      coupled oscillations were significantly lower in patients with sepsis compared
      with controls and correlated with outcome. This correlation was not independent
      when adjusting for severity of sepsis. CONCLUSIONS: Sepsis is associated with
      lower variability of both heart rate and RAP on EEG and reduction of their
      coupled oscillations. This uncoupling is associated with the severity of
      encephalopathy. Combined EEG and electrocardiogram monitoring may be used to gain
      insight in underlying mechanisms of sepsis and quantify brainstem or thalamic
      dysfunction.

PMID- 28520633
TI  - Insular Cortex Surgery for the Treatment of Refractory Epilepsy.
AB  - Focal epilepsy originating from the insular cortex is rare. One reason is the
      small amount of cortical tissue compared with other lobes of the brain. However,
      the incidence of insular epilepsy might be underestimated because of diagnostic
      difficulties. The semiology and the surface EEG are often not meaningful or even
      misleading, and elaborated imaging might be necessary. The close connections of
      the insular cortex with other potentially epileptogenic areas, such as the
      temporal lobe or frontal/central cortex, is increasingly recognized as possible
      reason for failure of epilepsy surgery for temporal or extratemporal seizures.
      Therefore, some centers consider invasive EEG recording of the insular cortex not
      only in case of insular epilepsy but also in other focal epilepsies with
      nonconclusive results from the presurgical work-up. The surgical approach to and
      resection of insular cortex is challenging because of its deep location and
      proximity to highly eloquent brain structures. Over the last decades, technical
      adjuncts like navigation tools, electrophysiological monitoring and
      intraoperative imaging have improved the outcome after surgery. Nevertheless,
      there is still a considerable rate of postoperative transient or permanent
      deficits, in some cases as unavoidable and calculated deficits. In most of the
      recent series, seizure outcome was favorable and comparable with extratemporal
      epilepsy surgery or even better. Up to now, the data volume concerning long-term
      follow-up is limited. This review focusses on the surgical challenges of
      resections to treat insular epilepsy, on prognostic factors concerning seizure
      outcome, on postoperative deficits and complications. Moreover, less invasive
      surgical techniques to treat epilepsy in this highly eloquent area are
      summarized.

PMID- 28520634
TI  - Associations Between Parental Factors and Child Diabetes-Management-Related
      Behaviors.
AB  - OBJECTIVE: Adherence to diabetes-management regimens in children requires
      teamwork and consistency from both parents and children. This study investigated
      a mediational model developed to understand the relationship between different
      modifiable parent factors influencing child diabetes-related behaviors. METHODS:
      We recruited 186 parents of children aged 2 to 10 years with Type 1 diabetes to
      complete self-report questionnaires on child diabetes behavior, parental self
      efficacy with managing the child's behavior, parent diabetes self-efficacy,
      parent adjustment, condition management effort, parent perception of their
      diabetes knowledge, and parenting behavior. We used structural equation modeling
      in AMOS to test our hypothesized model of interrelationships between variables
      associated with child diabetes behavior. RESULTS: The hypothesized model provided
      good fit to the data. We found that parent perception of low levels of diabetes
      knowledge and higher levels of condition management effort, and parent adjustment
      difficulties were associated with lower parental self-efficacy with diabetes
      management. This was further linked with lower levels of parental self-efficacy
      with managing their child's diabetes behavior, and consequently, higher extent of
      child diabetes behavior problems. Contrary to our expectations, we did not find a
      significant effect of parenting behavior on child diabetes behavior problems,
      either directly or indirectly via parent self-efficacy for managing child's
      behavior. CONCLUSION: Our findings shed light on the mechanisms through which
      different parenting factors interact and are associated with diabetes behavior in
      children. These factors can be targeted through parenting interventions to
      improve child's cooperation with diabetes-management tasks and reduce barriers to
      effective management.

PMID- 28520636
TI  - Commentary on "Counterbalanced Comparison of the Bayley Scales of Infant
      Development-II and -III at 18 to 22 Months Corrected Age".

PMID- 28520635
TI  - Decreasing Disparities in Child Development Assessment: Identifying and
      Discussing Possible Delays in the Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC).
AB  - OBJECTIVE: To assess how staff at the Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC) address potential developmental delays and
      parent developmental concerns in children <5 years. METHODS: A Web-based survey
      of Oregon WIC staff in nonadministrative roles assessed staff interactions with
      parents regarding concerning child development/behavior, perceptions of
      connectedness with local developmental resources, and knowledge of typical child
      development. RESULTS: Staff (N = 153) responses indicated knowledge of typical
      child development, frequent interactions with families about child development,
      and frequent noticing of developmental concerns. However, most staff reported
      being less than very well connected to developmental resources. Open-ended
      responses suggested that staff frequently make direct referrals to early
      intervention, public health nurses, and others who can further assess
      developmental concerns. CONCLUSION: Although it is outside the primary scope of
      their work, developmental and behavioral concerns are frequently raised and
      addressed by WIC staff. Findings suggest that strengthening the existing referral
      processes and enhancing continuity of care between WIC and developmental
      providers may improve child outcomes and reduce disparities.

PMID- 28520637
TI  - Clinical experience of stereotactic radiosurgery at a linear accelerator for
      intraocular melanoma.
AB  - Long-term results with linear accelerator LINAC-based stereotactic radiosurgery
      for intraocular uveal malignant melanoma were assessed. A retrospective study was
      carried out of patients with uveal melanoma after a 1-day session stereotactic
      radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150
      patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma)
      was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2
      to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from
      2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose
      volume histogram. Older age at treatment was correlated with the largest basal
      tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic
      irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years,
      and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary
      because of complications (secondary glaucoma). Enucleation-free interval ranged
      from 1 to 6 years. The median age at death was lower (65.7 years) for patients
      who died from metastatic disease than for those who died from any other cause
      (75.0 years). Survival rates at 5-year intervals and the need for secondary
      enucleation because of complications after linear accelerator irradiation are
      comparable to other techniques.

PMID- 28520638
TI  - EFFECTS OF INTRAVITREAL RANIBIZUMAB AND BEVACIZUMAB ON THE RETINAL VESSEL SIZE IN
      DIABETIC MACULAR EDEMA.
AB  - PURPOSE: The goal of this study was to assess the effects of a single injection
      of intravitreal ranibizumab (RAN) or bevacizumab (BEV) on the retinal vessel size
      in eyes with diabetic macular edema. MATERIALS AND METHODS: In total, 32 patients
      were enrolled in the RAN group, and 30 patients were included in BEV group. Each
      of these groups was also subdivided into two others groups: a study group and a
      control group. The study groups were composed of the injected eyes, whereas the
      noninjected fellow eyes served as the control groups. The patients underwent
      complete ophthalmic examinations, including optical coherence tomography and
      fundus fluorescein angiography, and the primary outcome measures included the
      central retinal artery equivalent, central retinal vein equivalent, and artery-to
      vein ratio. RESULTS: In the RAN study group (n = 32), the preinjection mean
      central retinal artery equivalent (175.42 MUm) decreased to 169.01 MUm after 1
      week, and to 167.47 MUm after 1 month (P < 0.001), whereas the baseline central
      retinal vein equivalent (235.29 MUm) decreased initially to 219.90 MUm after 1
      week, and to 218.36 MUm after 1 month (P < 0.001). In the BEV study group (n =
      30), the preinjection central retinal artery equivalent (150.21 MUm) decreased to
      146.25 MUm after 1 week, and to 145.89 MUm after 1 month (P < 0.001); whereas the
      baseline central retinal vein equivalent (211.87 MUm) decreased initially to
      204.59 MUm after 1 week and was 205.24 MUm after 1 month (P < 0.001). The
      preinjection artery-to-vein ratio values changed significantly (P = 0.001) after
      1 week and after 1 month in the RAN group, but no significant alteration in the
      artery-to-vein ratio was observed in the BEV group (P = 0.433). In both the RAN
      (n = 32) and BEV (n = 30) control groups, none of the 3 parameters changed
      throughout the study period, when compared with the baseline. CONCLUSION: The
      results of this study showed that both RAN and BEV injections significantly
      constricted the retinal blood vessel diameters.

PMID- 28520639
TI  - WRINKLED VASCULARIZED RETINAL PIGMENT EPITHELIUM DETACHMENT PROGNOSIS AFTER
      INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.
AB  - BACKGROUND/PURPOSE: Neovascular age-related macular degeneration (nAMD) is
      frequently associated with vascularized pigment epithelial detachment (v-PED). We
      observed a peculiar characteristic of v-PED characterized by small lacy folds of
      the retinal pigment epithelium, appearing as a wrinkled PED (w-PED) on spectral
      domain optical coherence tomography (SD-OCT). Our purpose was to describe the
      visual prognosis and number of intravitreal injections in w-PED compared with non
      w-PED. METHODS: In this retrospective, case-control series, we reviewed
      retrospectively medical records of 52 eyes of 51 patients who were consecutively
      included between November 1 and 30, 2015 with a previous minimum 3-year follow
      up. Inclusion criteria were: neovascular age-related macular degeneration,
      affected with w-PED. Baseline characteristics, best-corrected visual acuity
      (BVCA), number of intravitreal anti-vascular endothelial growth factor injections
      (anti-VEGF IVT) and maximal recurrence-free interval, that is, without
      intravitreal anti-vascular endothelial growth factor injection, were analyzed. A
      w-PED was defined as a v-PED >=200 MUm in height on SD-OCT imaging, presenting
      with at least 4 small lacy folds on the surface of the retinal pigment
      epithelium. Patients were compared with a control group, that is, patients
      harboring PED without wrinkle shape (non-w-PED). All patients had been treated by
      intravitreal anti-vascular endothelial growth factor injection of either
      ranibizumab (IVR) or aflibercept (IVA) using a pro re nata (PRN) protocol after
      three initial monthly treatments, with a minimum of follow-up of 3 years.
      RESULTS: Two groups of patients were compared, w-PED (29 eyes, from 29 patients),
      and non-w-PED (23 eyes from 22 patients). In the w-PED group, mean BCVA evolved
      from 0.28 (+/-0.18) log MAR (20/40, range 20/25-20/63) at baseline, to 0.29 (+/
      0.21) log MAR (20/40, range 20/25-20/63) at 1 year (P = 0.41), 0.34 (+/-0.26) log
      MAR (20/40, range 20/25-20/80) at 2 years (P = 0.49), 0.35 (+/-0.28) log MAR
      (20/40, range 20/25-20/80) at 3 years (P = 0.54). In the non-w-PED group, mean
      BCVA was 0.40 (+/-0.28) log MAR (20/50, range 20/25-20/100) at baseline and
      decreased to 0.48 (+/-0.46) log MAR (20/63, range 20/20-20/160) at 1 year (P =
      0.19), 0.48 (+/-0.35) log MAR (20/63, range 20/25-20/125) at 2 years (P = 0.02),
      0.60 (+/-0.38) log MAR (20/80, range 20/32-20/200) at 3 years (P = 0.002). In the
      w-PED group, the mean maximal documented recurrence-free interval was 7.87 (+/
      2.94) months at Year 1, 13.5 (+/-7.52) at Year 2 and 14.78 (+/-10.70) at Year 3,
      versus 4.59 (+/-2.95) months at Year 1, 7.83 (+/-6.62) at Year 2, 8.57 (+/-11.18)
      at Year 3 in the non-w-PED group (P = 0.0004; 0.0101; 0.0168 respectively at
      Years 1, 2 and 3). DISCUSSION: The evolution of v-PED after intravitreal anti
      vascular endothelial growth factor injection is still difficult to predict
      despite intense clinical research in this topic. In our study, we noticed that w
      PED might be a phenotypic prognosis factor for better visual acuity and longer
      maximal recurrence-free interval.

PMID- 28520640
TI  - TWENTY-FOUR MONTH FOLLOW-UP OF TOCILIZUMAB THERAPY FOR REFRACTORY UVEITIS-RELATED
      MACULAR EDEMA.
AB  - BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6
      receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular
      edema (ME). METHODS: Data were obtained by standardized chart review. Patients
      with quiescent uveitis seen at a single tertiary referral center, for whom ME was
      the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal
      thickness measured by optical coherence tomography; degree of anterior and
      posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working
      Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of
      resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6,
      12, 18, and 24. RESULTS: Sixteen eyes from 12 patients (10 women) were included.
      Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients
      achieved 24 months of follow-up and that is the census date for data collection.
      Before TCZ was commenced, ME was present, and all patients had been previously
      treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses
      were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot
      chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia
      (n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%;
      confidence interval) was 516 +/- 55 MUm at baseline, improving to 274 +/- 13 at
      Month 12 (P = 0.0004), and sustained at 274 +/- 14 at Month 24 of follow-up (P =
      0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual
      acuity improved from 0.78 +/- 0.18 (Snellen 20/120 +/- 20/30) at baseline to 0.42
      +/- 0.17 (20/52 +/- 20/30) at Month 12 (P = 0.0001) and 0.40 +/- 0.17 (20/50 +/-
      20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn
      in 5 patients with sustained remission at Month 12 but in all, ME relapsed
      between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions
      led to recovery of uveitis control and ME resolution. Two adverse events were
      reported during two 4-month follow-ups: one Grade 1 neutropenia and one community
      acquired pneumonia. CONCLUSION: In this long-term study, TCZ was effective and
      had a comparable safety profile to published data for TCZ use in other
      indications, when used for the treatment of refractory uveitis-related ME.

PMID- 28520641
TI  - FIVE-YEAR FOLLOW-UP AFTER EPIRETINAL MEMBRANE SURGERY: A Single-Center
      Experience.
AB  - PURPOSE: To evaluate the rate of epiretinal membrane (ERM) recurrence in eyes
      that underwent ERM peeling surgery at least 5 years earlier. METHODS:
      Retrospective interventional case series study of 37 patients (15 women and 22
      men; mean age, 70 +/- 7.6 years) operated on for ERM removal with a follow-up of
      at least 5 years. The patients underwent testing for visual acuity, an ophthalmic
      examination, and optical coherence tomography imaging, all of which were assessed
      preoperatively, postoperatively, and at the 5-year follow-up. RESULTS: Visual
      acuity significantly improved at 1 year after peeling compared with baseline (P =
      0.045), and the improved results were maintained at 5 years (P = 0.804) 0.766
      logarithm of the minimum angle of resolution (Snellen 6/35). The central macular
      thickness decreased significantly at the 1-year follow-up compared with baseline
      and continued to decrease as measured at the 5-year follow-up (P = 0.04). At 5
      years, the ERM recurrence rate reached 58% (28% extrafoveal). Photoreceptor
      atrophy and retinal pigment epithelium changes correlated with diabetes mellitus
      (P = 0.028). CONCLUSION: The recurrence rate of ERM after peeling surgery was
      reported as being around 5% to 12%. It was 58% in the current study. Because the
      recurrent ERM is generally mild, visual acuity was unaffected.

PMID- 28520642
TI  - INFLAMMATORY CHOROIDAL NEOVASCULAR MEMBRANE: Long-Term Visual and Anatomical
      Outcomes After Intravitreal Anti-vascular Endothelial Growth Factor Therapy.
AB  - PURPOSE: To assess the long-term visual and anatomical outcomes after
      intravitreal anti-vascular endothelial growth factor therapy for inflammatory
      choroidal neovascular membrane (CNVM). METHODS: Retrospective case series of 15
      consecutive cases of newly diagnosed inflammatory CNVM who were treated with
      intravitreal bevacizumab or ranibizumab injections. RESULTS: The study included 8
      women and 7 men with mean age at presentation with CNVM of 40.53 +/- 17.46 years
      (range, 11-70 years), and mean follow-up duration after anti-vascular endothelial
      growth factor therapy was 20.53 +/- 14.53 months (range, 6-48 months). All eyes
      had classic CNVM confirmed by fluorescein angiography, most commonly located in
      the peripapillary area (8 eyes, 53.3%), followed by juxtafoveal (4 eyes, 26.7%),
      and subfoveal location (3 eyes, 20%). All CNVMs showed complete resolution with
      mean 2.6 +/- 1.2 injections per eye. Preinjection mean best-corrected visual
      acuity of logarithm of minimum angle of resolution 0.79 +/- 0.76 (approximate
      Snellen equivalent 20/123) and mean central macular thickness of 435.9 +/- 190.2
      MUm improved significantly to mean best-corrected visual acuity of logarithm of
      minimum angle of resolution 0.46 +/- 0.43 (approximate Snellen equivalent 20/58)
      and mean central macular thickness of 262.13 +/- 108.70 MUm (P value 0.02 and
      <0.0001, respectively) at the final visit. Recurrence was seen in 26.7% eyes
      (4/15), all of which regressed with single injection. Only complication noted was
      subretinal fibrosis in one eye (6.7%). CONCLUSION: For inflammatory CNVM, in
      addition to immunosuppression in cases with active inflammation, anti-vascular
      endothelial growth factor therapy seems as a very effective treatment modality
      resulting in significant visual improvement and foveal flattening. Incidence of
      major complications is rare, and the recurrence rate seems low.

PMID- 28520643
TI  - Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha
      Particle-emitting Radionuclides.
AB  - BACKGROUND: Carcinogenic risks of internal exposures to alpha-emitters (except
      radon) are poorly understood. Since exposure to alpha particles-particularly
      through inhalation-occurs in a range of settings, understanding consequent risks
      is a public health priority. We aimed to quantify dose-response relationships
      between lung dose from alpha-emitters and lung cancer in nuclear workers.
      METHODS: We conducted a case-control study, nested within Belgian, French, and UK
      cohorts of uranium and plutonium workers. Cases were workers who died from lung
      cancer; one to three controls were matched to each. Lung doses from alpha
      emitters were assessed using bioassay data. We estimated excess odds ratio (OR)
      of lung cancer per gray (Gy) of lung dose. RESULTS: The study comprised 553 cases
      and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean:
      8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for
      uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)-adjusted for external
      radiation, socioeconomic status, and smoking-was 11 (2.6, 24) for total alpha
      dose, 50 (17, 106) for plutonium, and 5.3 (-1.9, 18) for uranium. CONCLUSIONS: We
      found strong evidence for associations between low doses from alpha-emitters and
      lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though
      confidence intervals overlap. Risk estimates were similar to those estimated
      previously in plutonium workers, and in uranium miners exposed to radon and its
      progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are
      somewhat larger than but consistent with those for atomic bomb survivors.See
      video abstract at, http://links.lww.com/EDE/B232.

PMID- 28520644
TI  - Trade-offs of Personal Versus More Proxy Exposure Measures in Environmental
      Epidemiology.
AB  - The technological ability to make personal measurements of toxicant exposures is
      growing rapidly. While this can decrease measurement error and therefore help
      reduce attenuation of effect estimates, we argue that as measures of exposure or
      dose become more personal, threats to validity of study findings can increase in
      ways that more proxy measures may avoid. We use directed acyclic graphs (DAGs) to
      describe conditions where confounding is introduced by use of more personal
      measures of exposure and avoided via more proxy measures of personal exposure or
      target tissue dose. As exposure or dose estimates are more removed from the
      individual, they become less susceptible to biases from confounding by personal
      factors that can often be hard to control, such as personal behaviors. Similarly,
      more proxy exposure estimates are less susceptible to reverse causation. We
      provide examples from the literature where adjustment for personal factors in
      analyses that use more proxy exposure estimates have little effect on study
      results. In conclusion, increased personalized exposure assessment has important
      advantages for measurement accuracy, but it can increase the possibility of
      biases from personal factors and reverse causation compared with more proxy
      exposure estimates. Understanding the relation between more and less proxy
      exposures, and variables that could introduce confounding are critical components
      to study design.

PMID- 28520645
TI  - Oxidative Stress and Breast Cancer Risk in Premenopausal Women.
AB  - BACKGROUND: Detrimental effects of oxidative stress are widely recognized, but
      induction of apoptosis and senescence may also have benefits for cancer
      prevention. Recent studies suggest oxidative stress may be associated with lower
      breast cancer risk before menopause. METHODS: We conducted a nested case-control
      study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of
      50,884 women. Premenopausal women ages 35-54 were eligible for selection. We
      matched controls 2:1 to cases on age and enrollment year and were breast cancer
      free at the time of the corresponding case's diagnosis. Oxidative stress was
      measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M)
      concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were
      calculated with multivariable conditional logistic regression. RESULTS: After
      multivariable adjustment for body mass index (BMI) and other potential
      confounders, the OR for breast cancer comparing the >90th (>=2.94 ng/mgCr) to
      <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and
      0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were
      associated with lower breast cancer risk among women who were also premenopausal
      (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06,
      0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among
      women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m
      (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m
      (OR: 0.98, CI: 0.39, 2.5, 138 cases). CONCLUSIONS: Together with other studies,
      our results support a possible inverse association between oxidative stress and
      premenopausal breast cancer risk.

PMID- 28520646
TI  - Relationship between pubertal timing and chronic nonspecific pain in adolescent
      girls: the Young-HUNT3 study (2006-2008).
AB  - The aim of this study was to examine a possible relationship between early
      puberty and chronic nonspecific pain in 13- to 18-year-old girls. All adolescents
      in Nord-Trondelag County, Norway, were invited to participate in the Young-HUNT3
      study (2006-2008). Of the invited girls, 81% answered the questionnaire and of
      these 3982 were 13 to 18 years of age. Menarche and perceived physical maturation
      were used as exposure measures. Early menarche was defined as <12 years, normal
      menarche as >=12 and <14 years, and late menarche as >=14 years. Perceived
      physical maturation was divided into maturing earlier, the same or later than
      others of their own age. The main outcome measure was chronic nonspecific pain,
      defined as pain in at least one location not related to any known disease or
      injury, for at least once a week during the last 3 months. The median age at
      menarche was 13.2 years. Chronic nonspecific pain was more prevalent among girls
      with early menarche (68%, 95% CI: 64%-72%) compared to girls with either normal
      (55%, 95% CI: 53%-57%), late (50%, 95% CI: 46%-54%), or no menarche (35%, 95% CI:
      29%-40%). The association persisted after adjusting for age, body mass index,
      socioeconomic factors, and anxiety and depression. A similar association was
      found between girls that perceived themselves as earlier physically matured than
      their peers and chronic nonspecific pain. Headache/migraine was the most common
      type of chronic nonspecific pain regardless of menarcheal age. In all reported
      locations, pain was more prevalent in the group with early menarche compared to
      normal or late menarche.

PMID- 28520647
TI  - Altered brain structure and function associated with sensory and affective
      components of classic trigeminal neuralgia.
AB  - Classic trigeminal neuralgia (CTN) is a chronic neuropathic pain state
      characterized by intense, piercing spasms of the orofacial region, and may be
      attributable to abnormal pain processing in the central nervous system. Our study
      investigated neuronal alterations using voxel-based morphometry (VBM), diffuse
      tensor imaging (DTI), and resting-state functional connectivity in 38 patients
      with CTN and 38 matched healthy controls. For voxel-based morphometry analyses,
      patients with CTN displayed gray matter volume (GMV) reductions in the anterior
      cingulate cortex (ACC) and mid-cingulate cortex, insula, secondary somatosensory
      cortex (S2), primary motor cortex (M1), premotor area, and several regions in the
      temporal lobe. For DTI analysis, patients compared with controls had increased
      mean diffusivity (MD) and decreased fractional anisotropy (FA) in the corpus
      callosum and the bilateral corona radiata, and increased mean diffusivity with no
      fractional anisotropy changes across the bilateral superior longitudinal
      fasciculus, the internal and external capsule, the thalamus and brainstem.
      Additionally, patients with CTN had enhanced functional connectivity between the
      right insula/S2 and ACC, medial prefrontal cortex, posterior cingulate cortex,
      and bilateral dorsolateral prefrontal cortex. Furthermore, gray matter volume of
      left inferior temporal gyrus negatively correlated with current pain intensity
      and disease duration in patients, and connectivity of the right insula/S2-ACC was
      negatively correlated with pain intensity, depression, and anxiety ratings. This
      study provides multiple lines of evidence supporting aberrant structural and
      functional patterns that are observed in patients with CTN, which may help us
      better understand the pathophysiology of CTN and facilitate the development of
      new therapies for this disease.

PMID- 28520648
TI  - A longitudinal study of the influence of comorbidities and lifestyle factors on
      low back pain in older men.
AB  - Older adults are largely under-represented in low back pain (LBP) research. In
      light of the ageing population, it is crucial to understand the influence of
      comorbidities and lifestyle factors on the risk and prognosis of LBP in older
      adults. The aims of this study were to describe the course of LBP in older men;
      to investigate whether comorbidities/lifestyle factors can predict the course of
      LBP in older men; to assess if comorbidities/lifestyle factors increase the risk
      of developing LBP in older men. The study sample comprised 1685 older men living
      in suburban Sydney, Australia. Low back pain, sociodemographic measures,
      lifestyle factors, and comorbidities were assessed. Of the 1012 men with LBP at
      baseline, 58% still reported having pain at the 24-month follow-up. Of those
      without pain at baseline (n = 673), 28% reported pain at follow-up. The odds of
      persistent pain at 24 months increased with each additional alcoholic drink/wk
      (odds ratio [OR] = 1.10, 95% confidence interval [CI]: 1.01-1.22; P = 0.03) and
      each additional unit of body mass index (OR = 1.28, 95% CI: 1.04-1.60; P = 0.02),
      but reduced for men who speak English at home (OR = 0.58, 95% CI: 0.35-0.96; P =
      0.03). In older men, free of LBP at baseline (n = 673), for every additional
      comorbidity there was an increased risk of developing LBP (OR = 1.17, 95% CI:
      1.00-1.37; P = 0.05). These results demonstrate the influence of lifestyle
      factors and comorbidities on LBP in older men and suggest that the consideration
      of these issues in management may improve outcomes.

PMID- 28520649
TI  - The Effectiveness and Feasibility of Endoscopic Ultrasound-guided Transgastric
      Drainage of Postoperative Fluid Collections Early After Pancreatic Surgery.
AB  - PURPOSES: To assess the feasibility and usefulness of endoscopic ultrasound
      guided transgastric drainage (EUS-GD) in patients who required early
      postoperative drainage of peripancreatic fluid collection or postoperative
      pancreatic fistulas after pancreatic surgery. PATIENTS AND METHODS: Between May
      2012 and January 2016, 33 patients who developed peripancreatic fluid collection
      or postoperative pancreatic fistulas after pancreatic resection underwent EUS-GD
      or percutaneous drainage (PTD). Outcomes were compared retrospectively. RESULTS:
      The drainage procedures were performed on postoperative day 4 to 71 (median, 12)
      in the EUS-GD group, and 7 to 35 (median, 14) in the PTD group. Technical and
      clinical success rates reached 92% (11/12) in the EUS-GD group, and 100% (21/21)
      in the PTD group with no complications or mortality. The duration of hospital
      stay after drainage was 10 to 44 (median, 15) days for EUS-GD, compared with 10
      to 39 (median, 21) days for PTD. CONCLUSIONS: EUS-GD is a safe and useful method
      for early drainage, which could be a good alternative to PTD.

PMID- 28520650
TI  - Balloon Dilatation of the Minor Duodenal Papilla Up to 4 mm is Safe in a Porcine
      Model.
AB  - OBJECTIVES: Balloon dilatation of the minor duodenal papilla is a treatment
      option for symptomatic pancreas divisum. The histologic effects of balloon
      dilatation have not yet been evaluated. The aim of this study is to investigate
      the tolerated extent of dilatation of the minor papilla. MATERIALS AND METHODS: A
      dilatation of the minor papilla was performed in freshly explanted pancreas of
      pigs using biliary balloon dilatators. Three organs were not dilated (control
      group), in each 8 organs a dilatation of 4, 6, and 8 mm, respectively, was
      performed. Tissue damage was assessed by microscopic evaluation. Ductal wall
      disruption and perforation as well as a semiquantitative inflammation score was
      described and compared. RESULTS: Ductal wall disruption was increased by
      dilatation of 6 (5/8; P=0.019) and 8 mm (6/8; P=0.006) compared with 4 mm (1/8).
      Median inflammation score was 0 (0 to 0), 1 (0 to 2), and 1 (0 to 2) for
      dilatation of 4, 6, and 8 mm, respectively (4 vs. 6 mm, P=0.007; 4 vs. 8 mm,
      P=0.026). No perforation occurred in the 4 (0/8) and 6 mm (0/8) group, 1
      perforation occurred in the 8 mm group (1/8). CONCLUSIONS: A dilatation of up to
      4 mm seems to be safe. However, dilatation of the minor papilla from 4 mm onwards
      is increasingly associated with tissue damage. These findings should be
      considered in endoscopic procedures dilating the minor duodenal papilla.

PMID- 28520651
TI  - Laparoscopic Management of Hepatocellular Carcinoma: A Critical Reappraisal.
AB  - Following the introduction of the first laparoscopic liver resection, after ~25
      years, a critical reappraisal seems to be warranted. Liver resection represents
      the first choice for curing early hepatocellular carcinoma (HCC) allowing a
      curative chance also in selected patients with intermediate stage tumors. The
      criteria for liver resectability by laparoscopy remains the same for open
      surgery, which is oncological criteria (absence of extrahepatic tumor location;
      completely resectable R0 resection), anatomic (resectability of involved segment
      with its own blood surely and biliary drainage; absence of vascular invasion of
      portal or hepatic veins) and technical (possibility to leave in place a residual
      volume >=40%). Anatomic resections being more challenging than wedged resections,
      were initially performed mainly for lesions located in the left liver (segments
      2, 3, and 4) and segments 5 and 6 of the right liver (anterior and lateral
      hepatic segments). Left lateral segmentectomy seemed most suited for laparoscopic
      resection because of the thinness of the liver, the possibility of resection
      without hilar dissection, ease of stapling the left hepatic vein and portal
      pedicles of segment II and III by mechanical stapling. Conversely, right
      hepatectomy seemed most difficult and technically challenging to perform. The
      analysis of literature confirms that minor liver resections for HCC can be safely
      conducted also in cirrhotic patients and that laparoscopy, when feasible, should
      be the approach of first choice. As mentioned, there have been several studies
      that compared the long-term outcomes of laparoscopic hepatectomy (LH) versus open
      hepatectomy for HCC, even in cirrhotic patients, showing that laparoscopy does
      not seem to have any impact on the risk of postoperative HCC recurrence. However,
      further studies seem to be required, especially for long-term oncological results
      and for major hepatectomy, before LH become a common alternative to open liver
      surgery. The practice of performing LH (major) is challenging, due to the
      significant complexity of these interventions.

PMID- 28520652
TI  - A Systematic Review and Meta-Analysis of Laparoscopic and Open Distal
      Pancreatectomy of Nonductal Adenocarcinomatous Pancreatic Tumor (NDACPT) in the
      Pancreatic Body and Tail.
AB  - BACKGROUND: Currently, laparoscopic distal pancreatectomy is regarded as a safe
      and effective surgical approach for lesions in the body and tail of the pancreas.
      This review examined the evidence from published data of comparative studies of
      laparoscopic versus open distal pancreatectomy of nonductal adenocarcinomatous
      pancreatic tumor in pancreatic body and tail. METHODS: A systematic review of the
      studies comparing laparoscopic and open distal pancreatectomy was conducted.
      Comparative studies published between January 1996 and June 2016 were included.
      Studies were selected on the basis of specific inclusion and exclusion criteria.
      These 2 techniques were compared regarding several outcomes of interest, which
      were divided into preoperative, operative, postoperative, and pathologic
      characteristics, postoperative biomarker, and hospital stay cost. Sensitivity and
      subgroup analysis partially confirmed the robustness of these data. RESULTS: Ten
      comparative case-control studies involving 712 patients (53.7% laparoscopic and
      46.3% open), who underwent a distal pancreatectomy were included. The results
      favored laparoscopy with regard to intraoperative blood loss (P=0.0001), the rate
      of blood transfusion (P=0.02), total hospital stay (P=0.004), postoperative
      hospital stay (P<0.0001), overall morbidity (P=0.0002), the rate of wound
      infection (P=0.05), time to initial feeds (P<0.0001), first flatus time
      (P=0.008), duration of pain-killer intake (P=0.0003), and C-reactive protein on
      postoperative day 1 (P=<0.0001). In the subgroup analysis, excluding western
      country studies, operation time changed to have a statistically significant
      difference between these 2 groups (P=0.02). CONCLUSIONS: Laparoscopic resection
      results in improved operative and postoperative outcomes compared with open
      surgery according to the results of the present meta-analysis. It may be a safe
      and feasible option for nonductal adenocarcinomatous pancreatic tumor patients in
      pancreatic body and tail. However, randomized controlled trials should be
      undertaken to confirm the relevance of these findings.

PMID- 28520653
TI  - Transenteric ERCP for Treatment of Choledocholithiasis After Duodenal Switch.
AB  - This article aims to describe step-by-step technique performed with the aid of a
      video. We report the performance of an endoscopic approach to the biliary tract
      on 2 patients who had previously undergone duodenal switch (DS). It was
      successfully performed a laparoscopic-assisted transenteric endoscopic retrograde
      cholangiopancreatography (ERCP) in both the patients. Although successful
      experiences with ERCP after Roux-en-Y gastric bypass have been found, few cases
      of ERCP after DS have been reported. Nevertheless, this is the first study to
      include a multimedia video with description of details and all technical steps of
      the transenteric ERCP performed on 2 patients who had previously undergone DS.
      Transenteric access is a feasible technique for reaching the biliary tract
      through endoscopy after DS. This technique could avoid most invasive and risky
      procedures. However, it requires a high level of therapeutic endoscopic training.

PMID- 28520655
TI  - Effectiveness of Intracavitary Electrocardiogram Guidance in Peripherally
      Inserted Central Catheter Tip Placement in Neonates.
AB  - Correct tip location is crucial for a peripherally inserted central catheter
      (PICC) to maximize the effects of central venous infusion. However, it is
      difficult to place the tip in a correct location in neonates because of the
      unreliable estimated length by surface landmark. Therefore, we evaluated the
      feasibility and safety of an improved intracavitary electrocardiogram (IC-ECG)
      technique in guiding PICC placement in neonates based on the ratios of P/R wave
      amplitudes on IC-ECG. The results showed that all of the 32 neonates whose PICCs
      had been successfully placed and correct tip position verified by chest
      radiography acquired qualified P wave on IC-ECG. The average ratio of P/R wave
      amplitude was 0.6 +/- 0.1, with a range of 0.4 to 0.8. The 49 neonates who
      received IC-ECG-guided PICC catheterization showed higher success rates of
      correct PICC tip position on the first attempt than traditional, predetermined
      length estimation on surface landmark (93.9% vs 62.5%, chi = 18.01, P < .001). No
      significant complications occurred in the studied neonates. Based on these
      findings, IC-ECG-guided tip placement appears to be a promising approach in
      improving the success rate of tip location when placing a PICC in neonates.

PMID- 28520654
TI  - Systematic Review of Hydrotherapy Research: Does a Warm Bath in Labor Promote
      Normal Physiologic Childbirth?
AB  - Health sciences research was systematically reviewed to assess randomized
      controlled trials of standard care versus immersion hydrotherapy in labor before
      conventional childbirth. Seven studies of 2615 women were included. Six trials
      examined hydrotherapy in midwifery care and found an effect of pain relief; of
      these, 2 examined analgesia and found reduced use among women who bathed in
      labor. One study each found that hydrotherapy reduced maternal anxiety and fetal
      malpresentation, increased maternal satisfaction with movement and privacy, and
      resulted in cervical dilation progress equivalent to standard labor augmentation
      practices. Studies examined more than 30 fetal and neonatal outcomes, and no
      benefit or harm of hydrotherapy was identified. Two trials had anomalous findings
      of increased newborn resuscitation or nursery admission after hydrotherapy, which
      were not supported by additional results in the same or other studies. Review
      findings demonstrate that intrapartum immersion hydrotherapy is a helpful and
      benign practice. Hydrotherapy facilitates physiologic childbirth and may increase
      satisfaction with care. Maternity care providers are recommended to include
      hydrotherapy among routine labor pain management options and consider immersion
      to promote progress of normal or protracted labor, particularly among women with
      preferences to avoid obstetric medications and procedures.

PMID- 28520656
TI  - The Power of a Parent's Touch: Evaluation of Reach and Impact of a Targeted
      Evidence-Based YouTube Video.
AB  - Despite strong evidence that skin-to-skin contact and breast-feeding are
      effective pain-relieving interventions for infants undergoing painful procedures,
      they remain underutilized in clinical practice. Given the important contribution
      of parents, there is a need to find innovative ways to assist parents to become
      actively involved in their infant's care. We developed a YouTube video to
      disseminate evidence-based information on the effectiveness of skin-to-skin
      contact and breast-feeding for infant pain management. The 2-minute 39-second
      video launched on December 2, 2014, and was promoted through Web-based and in
      person communication and YouTube advertisements. Data were collected using
      YouTube analytics and an online survey. Post-18 months from its launch, the video
      had a reach of 157 938 views from 154 countries, with most viewers watching an
      average of 73% of the video (1 minute 56 seconds). Parents (n = 32) and
      healthcare providers (n = 170) completed the survey. Overall, both reported that
      they liked the video, found it helpful, felt more confident, and were more likely
      to use skin-to-skin contact (16% and 12%) and breast-feeding (3% and 11%),
      respectively, during future painful procedures. Despite the high-viewing
      patterns, alternative methods should be considered to better evaluate the impact
      on practice change.

PMID- 28520657
TI  - CT-based Techniques for Brain Perfusion.
AB  - Recent rapid advances in endovascular treatment for acute ischemic stroke
      highlight the crucial role of neuroimaging especially multimodal computed
      tomography (CT) including CT perfusion in stroke triage and management decisions.
      With an increasing focus on changes in cerebral physiology along with time-based
      matrices in clinical decisions for acute ischemic stroke, CT perfusion provides a
      rapid and practical modality for assessment and identification of salvageable
      tissue at risk and infarct core and provides a better understanding of the
      changes in cerebral physiology. Although there are challenges with the lack of
      standardization and accuracy of quantitative assessment, CT perfusion is evolving
      as a cornerstone for imaging-based strategies in the rapid management of acute
      ischemic stroke.

PMID- 28520659
TI  - Predictors of Satisfaction With Life in Veterans After Traumatic Brain Injury: A
      VA TBI Model Systems Study.
AB  - OBJECTIVE: To identify predictors of satisfaction with life in Veterans 1 year
      after traumatic brain injury (TBI). SETTING: The VA TBI Model Systems (TBIMS)
      project includes 5 Veterans Affairs (VA) Polytrauma Rehabilitation Centers.
      PARTICIPANTS: Veterans enrolled in the VA TBIMS study who completed the
      Satisfaction With Life Scale at year 1 follow-up. The sample is largely male
      (96%) and Caucasian (72%), with a median age of 27 years upon enrollment. DESIGN:
      Prospective observational cohort study measuring including demographics (eg,
      education), preinjury variables (eg, mental health history and employment), and
      military variables (eg, injury during deployment and injury during active duty
      status). MAIN OUTCOME MEASURE: Satisfaction With Life Scale. RESULTS:
      Multivariate regression analyses revealed that age, marital status, preinjury
      employment status, preinjury mental health history, and active duty status at the
      time of injury were significant predictors of life satisfaction at year 1 follow
      up. CONCLUSIONS: Results of this study suggest that satisfaction with life in
      Veterans with TBI is mediated by several factors that might inform rehabilitation
      interventions and discharge recommendations. Preinjury variables and active duty
      status (a unique aspect of the Veteran population) influence life satisfaction at
      1 year postinjury. Limitations and future clinical implications will be
      discussed.

PMID- 28520658
TI  - Age-Group and Gender Differences in Stroke Knowledge in an Israeli Jewish Adult
      Population.
AB  - BACKGROUND: Stroke is a leading cause of long-term disability and the fifth
      leading cause of death in Israel. Knowledge of stroke warning signs has been
      linked to early seeking of medical help. Little is known about knowledge of
      stroke warning signs in Israeli Jewish adults. METHODS: Stroke knowledge was
      examined among Jewish Israeli adults. Using a structured questionnaire,
      registered nurses interviewed a convenience sample of the respondents, 18 years
      or older, with no stroke history. Stroke knowledge and demographics were examined
      by 3 age groups (<45, 45-64, and >64 years) in men and women. RESULTS: In total,
      1137 Jewish Israelis were interviewed, 457 (40.2%) men and 680 women (59.8%); 493
      (43.4%) were younger than 45 years, 541 (47.6%) were aged 45 to 64 years, and 102
      (9%) were older than 64 years; 1 (0.1%) did not report age. On average, each
      interview lasted for 25 to 30 minutes. Participants younger than 45 years showed
      the lowest knowledge of stroke cause. Women younger than 45 years were less
      likely to identify at least 2 stroke warning signs. Participants younger than 45
      years were less likely to identify at least 2 risk factors, compared with
      participants aged 45 to 64 years and older than 64 years. Women younger than 45
      years were less likely to identify at least 2 stroke prevention strategies.
      CONCLUSION: Participants younger than 45 years showed the lowest levels of stroke
      knowledge. The highest stroke knowledge was found in the 45 to 64 years age
      group. Stroke knowledge among different age groups was similar in both genders.
      Educational campaigns aimed at increasing knowledge of stroke among the general
      population and targeting the younger population are recommended.

PMID- 28520660
TI  - Childhood Trauma and Lifetime Traumatic Brain Injury Among Individuals Who Are
      Homeless.
AB  - OBJECTIVES: To study the association of childhood trauma and lifetime prevalence
      of traumatic brain injury (TBI) among individuals who are homeless. DESIGN: Cross
      sectional survey. SETTING: Three cities in British Columbia, Canada.
      PARTICIPANTS: Five hundred individuals who are homeless and 19 years of age or
      older in 2009. MEASUREMENTS: Traumatic brain injury was identified with National
      Survey of Homeless Assistance Providers and Clients (NSHAPC) and childhood trauma
      using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). The relationship
      between childhood trauma and TBI was explored using multivariable logistic
      regression approach, adjusting for age, gender, any psychiatric diagnosis
      (anxiety disorder, mood disorder, psychosis), alcohol dependence, and substance
      dependence. The effect of number of childhood trauma types on TBI was also
      explored using multiple variables logistic regression approach adjusting for the
      same covariates. RESULTS: The prevalence of TBI was 63.6% and childhood
      maltreatment was 87.7% among the sample population. During childhood of 487
      participants included in the analysis, 57.7% experienced physical abuse, 62.8%
      physical neglect, 45.8% sexual abuse, 62.4% emotional abuse, and 55.2% emotional
      neglect. After adjustment, childhood trauma (adjusted odds ratio [aOR] = 2.26;
      95% confidence interval [CI], 1.04-5.02), childhood physical abuse (aOR = 2.13;
      95% CI, 1.19-3.87; n = 487), and childhood emotional abuse (aOR = 1.95; 95% CI,
      1.09-3.51; n = 487) were significantly associated with history of TBI. After
      adjustment, having 4 different types of childhood trauma (aOR = 2.81; 95% CI,
      1.11-7.31) was significantly associated with higher odds of reporting TBI
      history. CONCLUSIONS: Childhood trauma is significantly associated with lifetime
      prevalence of TBI in homeless populations in British Columbia, Canada, indicating
      an added level of vulnerability in this population. In addition, these findings
      suggest a potential role for childhood trauma prevention strategies and services
      mindful of the patients' history of trauma for this particularly vulnerable
      population.

PMID- 28520661
TI  - Traumatic Brain Injury and Depression in a Community-Based Sample: A Cohort Study
      Across the Adult Life Span.
AB  - OBJECTIVES: To determine whether self-reported traumatic brain injuries (TBIs)
      are associated with "cases" of clinically significant depression in the general
      community. To examine interactions between variables previously linked to
      depression after a TBI. SETTING: Population-based community study (Canberra and
      Queanbeyan, Australia). PARTICIPANTS AND DESIGN: Three age cohorts: young, middle
      aged, and older adults (aged 20-24, 40-44, and 60-64 years at baseline) randomly
      selected from the electoral roll and followed across 3 waves (4 years apart). A
      total of 7397, 6621, and 6042 people provided their TBI history in waves 1 to 3.
      MEASURES: Lifetime (TBIlifetime: sustained at any time since birth), recent
      (TBIrecent: in the preceding 4 years), and multiple (TBImultiple: more than 1)
      TBIs, current depression, and known risk factors for depression (age, sex,
      marital/employment status, prior history of depression, medical conditions,
      recent life events, alcohol consumption, social support, physical activity).
      RESULTS: Generalized estimating equations demonstrated a significant association
      between sustaining a TBI and experiencing clinically significant depression
      (cases), even after controlling for multiple demographic and health/lifestyle
      factors. CONCLUSION: There is an enduring association between depression and TBI,
      suggesting that, following a TBI, individuals should be monitored and supported
      to optimize their long-term psychological health.

PMID- 28520662
TI  - Anxiety Disorders in Adults With Childhood Traumatic Brain Injury: Evidence of
      Difficulties More Than 10 Years Postinjury.
AB  - OBJECTIVE: To explore long-term psychiatric outcomes in individuals with a
      history of childhood traumatic brain injury (TBI) or orthopedic injury (OI).
      SETTING: Hospital emergency department, medical admission records and outpatient
      settings. PARTICIPANTS: There were 95 males (M = 22.78 years, SD = 3.44 years)
      and 74 females (M = 22.27 years, SD = 3.09 years), 65 with mild TBI (M = 23.25
      years, SD = 3.58 years), 61 with moderate-severe TBI (M = 22.34 years, SD = 2.79
      years), and 43 with OI (M = 21.81 years, SD = 3.36 years). DESIGN: Longitudinal,
      between-subjects, cross-sectional design using retrospective and current data.
      MAIN MEASURES: Semistructured interview to obtain psychiatric diagnoses and
      background information, and medical records for identification of TBI. RESULTS:
      Group with moderate-severe TBI presented with significantly higher rates of any
      anxiety disorder (chi2 = 6.81, P = .03) and comorbid anxiety disorder (chi2 =
      6.12, P < .05). Group with overall TBI presented with significantly higher rates
      of any anxiety disorder (chi1 = 5.36, P = .02), panic attacks (chi1 = 4.43, P =
      .04), specific phobias (chi1 = 4.17, P = .04), and depression (chi1 = 3.98, P <
      .05). Prediction analysis revealed a statistically significant model (chi7 =
      41.84, P < .001) explaining 23% to 37% of the variance in having any anxiety
      disorder, with significant predictors being group (TBI) and gender (female).
      CONCLUSIONS: Children who have sustained a TBI may be vulnerable to persistent
      anxiety, panic attacks, specific phobias, and depression, even 13 years after the
      injury event.

PMID- 28520663
TI  - Contributions to Executive Dysfunction in Operation Enduring Freedom/Operation
      Iraqi Freedom Veterans With Posttraumatic Stress Disorder and History of Mild
      Traumatic Brain Injury.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD), history of mild traumatic brain
      injury (mTBI), and executive function (EF) difficulties are prevalent in
      Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We
      evaluated the contributions of injury variables, lower-order cognitive component
      processes (processing speed/attention), and psychological symptoms to EF.
      PARTICIPANTS: OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were
      administered neuropsychological tests of EF and self-report assessments of PTSD
      and depression. RESULTS: Those impaired on one or more EF measures had higher
      PTSD and depression symptoms and lower processing speed/attention performance
      than those with intact performance on all EF measures. Across participants,
      poorer attention/processing speed performance and higher psychological symptoms
      were associated with worse performance on specific aspects of EF (eg, inhibition
      and switching) even after accounting for injury variables. Although direct
      relationships between EF and injury variables were equivocal, there was an
      interaction between measures of injury burden and processing speed/attention such
      that those with greater injury burden exhibited significant and positive
      relationships between processing speed/attention and inhibition/switching,
      whereas those with lower injury burden did not. CONCLUSION: Psychological
      symptoms as well as lower-order component processes of EF (attention and
      processing speed) contribute significantly to executive dysfunction in OEF/OIF
      Veterans with PTSD and history of mTBI. However, there may be equivocal
      relationships between injury variables and EF that warrant further study. Results
      provide groundwork for more fully understanding cognitive symptoms in OEF/OIF
      Veterans with PTSD and history of mTBI that can inform psychological and
      cognitive interventions in this population.

PMID- 28520664
TI  - Follow-Up Care Adherence After Hospital Discharge in Children With Traumatic
      Brain Injury.
AB  - OBJECTIVE: To investigate factors associated with follow-up care adherence in
      children hospitalized because of traumatic brain injury (TBI). DESIGN: An urban
      level 1 children's hospital trauma registry was queried to identify patients (2
      18 years) hospitalized with a TBI in 2013 to 2014. Chart reviewers assessed
      discharge summaries and follow-up instructions in 4 departments. MAIN MEASURES:
      Three levels of adherence-nonadherence, partial adherence, and full adherence-and
      their associations with care delivery, patient, and injury factors. RESULTS: In
      our population, 80% were instructed to follow up within the hospital network.
      These children were older and had more severe TBIs than those without follow-up
      instructions and those referred to outside providers. Of the 352 eligible
      patients, 19.9% were nonadherent, 27.3% were partially adherent, and 52.8% were
      fully adherent. Those recommended to follow up with more than 1 department had
      higher odds of partial adherence over nonadherence (adjusted odds ratio [AOR] =
      5.8, 95% CI: 1.9-17.9); however, these patients were less likely to be fully
      adherent (AOR = 0.1; 95% CI: 0.1-0.3). Privately insured patients had a higher
      AOR of full adherence. CONCLUSIONS: Nearly 20% of children hospitalized for TBI
      never returned for outpatient follow-up and 27% missed appointments. Care
      providers need to educate families, coordinate service provision, and promote
      long-term monitoring.

PMID- 28520665
TI  - Family History of Migraine Associated With Posttraumatic Migraine Symptoms
      Following Sport-Related Concussion.
AB  - OBJECTIVE: To determine whether family history of migraine increased the
      likelihood of posttraumatic migraine (PTM) symptom presentation in adolescents
      following concussion, and examine the influence of family history of migraine and
      PTM on postinjury outcomes. SETTING: Outpatient concussion clinic. PARTICIPANTS:
      A total of 153 patients with concussion (103 males and 50 females) aged 15.72 +/-
      1.48 years (range 12-18 years). DESIGN: Cross-sectional, observational study of
      patients presenting for initial evaluation 4.72 +/- 3.05 days (range 1-14)
      postinjury. MAIN MEASURES: Computerized neurocognitive testing, symptom report,
      and vestibular/oculomotor screening. RESULTS: Patients with a family history of
      migraine were 2.6 times (odds ratio = 2.60, confidence interval = 1.35-5.02, P =
      .003) more likely to present with PTM compared with patients without a family
      history. Results of multivariate analyses of covariance, controlling for
      concussion history, revealed significant main effects for PTM on (1) Immediate
      Post-Concussion Assessment and Cognitive Testing (ImPACT)/Post-Concussion Symptom
      Scale (PCSS) (F = 15.43, P <.001) and (2) Vestibular/Ocular Motor Screening
      (VOMS) (F = 8.52, P < .001). There was no main effect for family history of
      migraine on ImPACT/PCSS (P = .22) and VOMS (P = .83) or interaction between
      family history of migraine and PTM on ImPACT/PCSS (P = .84) and VOMS (P = .52).
      CONCLUSION: Family history of migraine is associated with PTM symptoms following
      sport-related concussion, suggesting a genetic predisposition for migraine may
      serve as a catalyst or trigger for onset of PTM. However, only presence of PTM,
      rather than family history of migraine, was related to worse neurocognitive and
      vestibular/oculomotor outcomes.

PMID- 28520667
TI  - Supervision Needs Following Veteran and Service Member Moderate to Severe
      Traumatic Brain Injury: A VA TBI Model Systems Study.
AB  - OBJECTIVE: To characterize supervision levels across residential settings at 1
      year post-TBI and explore predictors of supervision in a Veteran and Service
      member population. SETTING: Five VA Polytrauma Rehabilitation Centers.
      PARTICIPANTS: A total of 302 individuals enrolled in the VA TBI Model Systems
      (TBIMS) research program. DESIGN: Prospective, longitudinal, multisite. MAIN
      MEASURES: Primary residence and supervision levels measured via scores on the
      Supervision Rating Scale. For predictive modeling, scores were dichotomized into
      2 groups: those that were fully independent/living alone or required only some
      supervision during the day (independent group, n = 195) and those that required
      overnight supervision, full-time indirect supervision, and full-time direct
      supervision (dependent group, n = 107). RESULTS: Thirty-five percent were
      receiving supervision at 1 year post-TBI across residential settings and 28% were
      living in alternative settings. Multivariate modeling indicated that older age
      and longer posttraumatic amnesia (PTA) were predictive of having a need for
      supervision at 1 year postinjury. CONCLUSIONS: Supervision needs are long-term
      features of moderate and severe TBI. Results of this study lend support to the
      shift toward conceptualizing TBI as a chronic disease.

PMID- 28520666
TI  - Anger Self-Management Training for Chronic Moderate to Severe Traumatic Brain
      Injury: Results of a Randomized Controlled Trial.
AB  - OBJECTIVE: To test efficacy of 8-session, 1:1 treatment, anger self-management
      training (ASMT), for chronic moderate to severe traumatic brain injury (TBI).
      SETTING: Three US outpatient treatment facilities. PARTICIPANTS: Ninety people
      with TBI and elevated self-reported anger; 76 significant others (SOs) provided
      collateral data. DESIGN: Multicenter randomized controlled trial with 2:1
      randomization to ASMT or structurally equivalent comparison treatment, personal
      readjustment and education (PRE). Primary outcome assessment 1 week
      posttreatment; 8-week follow-up. PRIMARY OUTCOME: Response to treatment defined
      as 1 or more standard deviation change in self-reported anger. SECONDARY
      OUTCOMES: SO-rated anger, emotional and behavioral status, satisfaction with
      life, timing of treatment response, participant and SO-rated global change, and
      treatment satisfaction. MAIN MEASURES: State-Trait Anger Expression Inventory
      Revised Trait Anger (TA) and Anger Expression-Out (AX-O) subscales; Brief Anger
      Aggression Questionnaire (BAAQ); Likert-type ratings of treatment satisfaction,
      global changes in anger and well-being. RESULTS: After treatment, ASMT response
      rate (68%) exceeded that of PRE (47%) on TA but not AX-O or BAAQ; this finding
      persisted at 8-week follow-up. No significant between-group differences in SO
      reported response rates, emotional/behavioral status, or life satisfaction. ASMT
      participants were more satisfied with treatment and rated global change in anger
      as significantly better; SO ratings of global change in both anger and well-being
      were superior for ASMT. CONCLUSION: ASMT was efficacious and persistent for some
      aspects of problematic anger. More research is needed to determine optimal dose
      and essential ingredients of behavioral treatment for anger after TBI.

PMID- 28520669
TI  - Investigating the Connection Between Traumatic Brain Injury and Posttraumatic
      Stress Symptoms in Adolescents.
AB  - OBJECTIVE: To identify potentially modifiable individual and social-environmental
      correlates of posttraumatic stress symptoms (PTSS) among adolescents hospitalized
      for traumatic brain injury (TBI). SETTING: Four pediatric hospitals and 1 general
      hospital in the United States. PARTICIPANTS: Children ages 11 to 18 years,
      hospitalized for moderate-severe TBI within the past 18 months. DESIGN:
      Retrospective cross-sectional analysis. MAIN MEASURES: The University of
      California at Los Angeles (UCLA) Post-traumatic Stress Disorder (PTSD) Reaction
      Index and the Youth Self-Report (YSR) PTSD subscale. RESULTS: Of 147 adolescents
      enrolled, 65 (44%) had severe TBI, with an average time since injury of 5.8 +/- 4
      months. Of the 104 who completed the UCLA-PTSD Reaction Index, 22 (21%) reported
      PTSS and 9 (8%) met clinical criteria for PTSD. Of the 143 who completed the YSR
      PTSD subscale, 23 (16%) reported PTSS and 6 (4%) met clinical criteria for PTSD.
      In multivariable analyses, having a negative approach to problem solving and
      depressive symptoms were both associated (P < .001) with higher levels of PTSS
      based on the UCLA-PTSD Reaction Index (beta = 0.41 and beta = 0.33, respectively)
      and the YSR-PTSD subscale (beta = 0.33 and beta = 0.40, respectively).
      CONCLUSION: Targeting negative aspects of problem solving in youths after brain
      injury may mitigate PTSS.

PMID- 28520668
TI  - Structural Connectivity Related to Persistent Symptoms After Mild TBI in
      Adolescents and Response to Aerobic Training: Preliminary Investigation.
AB  - OBJECTIVE: To quantify structural connectivity abnormalities in adolescents with
      mild traumatic brain injury (mTBI) and to investigate connectivity changes
      following aerobic training using graph theory and diffusion tensor imaging
      tractography. SETTING: Outpatient research setting. PARTICIPANTS: Twenty-two
      children (age: 15.83 +/- 1.77 years, 10 females) with 4 to 16 weeks of persistent
      symptoms after mTBI and a matched healthy comparison group. DESIGN: Randomized
      clinical trial of aerobic training and stretching comparison combined with case
      control comparison. MAIN MEASURES: (1) Five global network measures: global
      efficiency (Eglob), mean local efficiency, modularity, normalized clustering
      coefficient (gamma), normalized characteristic path length (lambda), and small
      worldness (sigma). (2) The self-reported Post-Concussion Symptom Inventory score.
      RESULTS: At initial enrollment, adolescents with mTBI had significantly lower
      Eglob and higher gamma, lambda, and sigma (all P < .05) than healthy peers. After
      the intervention, significantly increased Eglob and decreased lambda (both P <
      .05) were found in the aerobic training group. Improvement in Post-Concussion
      Symptom Inventory scores was significantly correlated with the Eglob increase and
      lambda decrease in the aerobic training and lambda decrease in the stretching
      comparison group (all P < .05). CONCLUSION: This pilot study showed initial
      evidence that structural connectivity analysis was sensitive to brain network
      abnormalities and may serve as an imaging biomarker in children with persistent
      symptoms after mTBI.

PMID- 28520670
TI  - Neutrophil to Lymphocyte Ratio as a Novel Predictor of Outcome in Patients With
      Severe Traumatic Brain Injury.
AB  - OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) has been reported to be a
      predictor of outcome in critical illness. Objective of this study was to
      investigate the changes of the NLR in patients with severe traumatic brain injury
      (TBI) and analyze the relationship between the NLR and TBI outcome. SETTING:
      China. PARTICIPANTS: A total of 855 patients with severe TBI from January 2007 to
      April 2012. DESIGN: Retrospective. MAIN MEASUREMENT: Data on the NLR and other
      indicators were collected. After follow-up until death or 1 year, the
      relationship between the NLR and TBI outcome was analyzed retrospectively.
      RESULTS: The final analysis included 688 patients. There were 508 (73.8%) who had
      an unfavorable outcome by 1 year after head trauma. The value of the NLR on
      admission was significantly higher in the unfavorable outcome group than in the
      favorable outcome group (P < .001). Multivariate logistic analysis showed that
      higher NLR was associated with an unfavorable outcome (odds ratio, 1.100; P <
      .001). Receiver operating characteristic curve analysis showed that the NLR had a
      sensitivity of 60.2% and a specificity of 71.1% for predicting unfavorable
      outcome at 1 year on the basis of the best threshold. CONCLUSION: The NLR might
      be useful as a novel predictor for 1-year outcome and mortality in severe TBI.

PMID- 28520671
TI  - Living Life After Traumatic Brain Injury: Phase 1 of a Longitudinal Qualitative
      Study.
AB  - OBJECTIVE: To explore what helps and hinders recovery and adaptation after
      disabling traumatic brain injury (TBI) and make recommendations for improving
      service responsiveness. DESIGN: A longitudinal qualitative descriptive study
      across all TBI severities. SETTING: Community. PARTICIPANTS: Forty people with
      TBI, and 22 significant others, 6 to 9 months following a TBI. MAIN MEASURES:
      Semistructured interviews, analyzed using qualitative description, focused on (a)
      key areas of importance or concern and (b) strategies or actions that people
      found helpful or that hindered recovery. RESULTS: Traumatic brain injury produced
      a complex set of challenges in keeping up with life, and understanding what
      having a TBI means for, and to, me. This period encompassed a tangled fit and
      misfit in life as brain injury did not occur in isolation. People had to actively
      change some aspects of life and yet allow other changes to happen. Valued
      supports from others included being looked out for and having someone to help
      drive the process. CONCLUSION: Improved services delivery and better outcomes may
      result if we respond to the person within his or her context; listen, believe,
      and acknowledge the person's story through our actions; and avoid assumptions
      about aspects of life that mean most to people and who/what may help best.

PMID- 28520673
TI  - Behavioral Clinical Trials in Moderate to Severe Pediatric Traumatic Brain
      Injury: Challenges, Potential Solutions, and Lessons Learned.
AB  - : The purpose of this commentary is to outline the challenges encountered when
      conducting clinical trials of interventions for pediatric traumatic brain injury
      (TBI) and share potential solutions for surmounting these issues. This commentary
      grows out of our experience implementing 8 randomized clinical trials (RCTs) of
      family-centered interventions to reduce child behavior problems and
      caregiver/parent distress following pediatric brain injury. These studies,
      involving more than 600 participants from 8 clinical centers, support the
      feasibility of conducting RCTs with children who have sustained TBIs while
      highlighting potential challenges and threats to validity. The challenges of
      behavioral trials for pediatric TBI are apparent but not insurmountable. Careful
      consideration of the clinical trial issues outlined in this commentary can inform
      design choices and analyses when planning a clinical trial. It is critically
      important that investigators share their failures as well their successes to move
      the field of pediatric TBI intervention research forward.

PMID- 28520672
TI  - Sertraline for Major Depression During the Year Following Traumatic Brain Injury:
      A Randomized Controlled Trial.
AB  - OBJECTIVE: Major depressive disorder (MDD) is common and associated with impaired
      functioning after traumatic brain injury (TBI). Few placebo-controlled
      antidepressant trials exist in this population. We evaluated the efficacy and
      tolerability of sertraline for MDD within 1 year of sustaining a TBI. SETTING:
      Level I trauma center. PARTICIPANTS: Adults with MDD within 1 year of
      hospitalization for complicated mild to severe TBI. DESIGN: Randomized, double
      blind, placebo-controlled trial. MAIN MEASURES: Twelve-week treatment response on
      the 17-item Hamilton Depression Rating Scale. We also assessed symptom
      improvement and remission. RESULTS: We randomized 62 participants: 32% sustained
      a severe TBI, 68% had significant anxiety, 63% had a history of prior MDD, and
      69% had a history of alcohol or drug dependence. Depression significantly
      improved from baseline to 12 weeks in both treatment groups (P < .001). There
      were no significant differences between the sertraline and placebo groups over 12
      weeks on depression severity, response, or remission. The sertraline group had
      significant improvement on speed of information processing compared with the
      placebo group (P < .006). CONCLUSION: Sertraline monotherapy was not superior to
      placebo for MDD in people with post-acute complicated mild to severe TBI.
      Research is needed on the effectiveness of interventions that also address the
      significant psychosocial needs of this population.

PMID- 28520676
TI  - Describing Weight Loss Attempts and Physical Activity Among Individuals With TBI
      Prior to Participation in a Weight-Loss Program.
AB  - OBJECTIVE: Describe (1) weight loss history, (2) perceptions about lifestyle
      changes, and (3) physical activity among a sample of individuals with traumatic
      brain injury prior to a 12-month lifestyle change program. SETTING: Community
      based. PARTICIPANTS: Individuals enrolled in a lifestyle change program, 6 months
      or more post-traumatic brain injury, body mass index of 25 or greater, 18 to 64
      years of age, with physician's clearance to participate. DESIGN: Convenience
      sample. MAIN MEASURES: Self-report data were collected before beginning the
      lifestyle change program including descriptive, weight loss history and physical
      activity behavior using the Modifiable Activity Questionnaire. RESULTS: The final
      sample included 22 participants (M age = 46 years) injured a median of 8 years
      ago. Mean weight was 208.5 lb (SD = 40.2), with average body mass index of 31.84
      (SD = 4.4). Since injury, 72.7% reported prior weight loss attempts, with 50%
      gaining 10 lb or more. All participants indicated high motivation for lifestyle
      changes. Perceived benefits included feeling better, improving overall health,
      and increased energy. Barriers included physical health complications. Types of
      physical activity completed included walking (68%, 180 min/mo) and swimming (32%,
      79 min/mo). CONCLUSION: Results indicate that many individuals gained weight
      since injury and attempted weight loss, demonstrating a need for evidence-based
      lifestyle interventions. Future research is needed to determine whether
      individuals with traumatic brain injury are able to achieve and maintain weigh
      loss through intervention.

PMID- 28520674
TI  - Relationship Stability After Traumatic Brain Injury Among Veterans and Service
      Members: A VA TBI Model Systems Study.
AB  - OBJECTIVE: To explore stability of relationships and predictors of change in
      relationship status 2 years following TBI/polytrauma. SETTING: Five Department of
      Veterans Affairs Polytrauma Rehabilitation Centers (VA PRCs). PARTICIPANTS: A
      total of 357 active duty service members and Veterans enrolled in the Veterans
      Affairs Polytrauma Rehabilitation Centers Traumatic Brain Injury Model Systems
      database with complete marital status information at 2 years postinjury. DESIGN:
      Prospective, longitudinal, multisite. MAIN MEASURES: Relationship status change
      was defined as change in marital status (single/never married; married;
      divorced/separated) at 2-year follow-up, compared with status at enrollment.
      RESULTS: At the time of enrollment, 134 participants (38%) were single/never
      married; 151 (42%) were married, and 72 (20%) were divorced/separated. Of those
      married at enrollment, 78% remained married at year 2 while 22% underwent
      negative change. Multivariable analyses revealed that age and education at the
      time of injury and mental health utilization prior to injury were significant
      predictors of relationship change. Among those who were single/divorced/separated
      at the time of enrollment, 87% remained so at year 2 while 13% underwent positive
      change. Injury during deployment significantly predicted positive relationship
      change. CONCLUSIONS: The unmalleable, preinjury characteristics identified may be
      used as potential triggers for education, prevention, surveillance, and couples
      therapy, if needed.

PMID- 28520675
TI  - The Role of Cognitive Reserve in Recovery From Traumatic Brain Injury.
AB  - OBJECTIVE: To examine whether cognitive reserve (CR) attenuates the initial
      impact of traumatic brain injury (TBI) on cognitive performance (neural reserve)
      and results in faster cognitive recovery rates in the first year postinjury
      (neural compensation), and whether the advantage of CR differs on the basis of
      the severity of TBI. SETTING: Inpatient/outpatient clinics at an academic medical
      center. PARTICIPANTS: Adults with mild TBI (mTBI; n = 28), complicated mild TBI
      (cmTBI; n = 24), and moderate to severe TBI (msevTBI; n = 57), and
      demographically matched controls (n = 66). DESIGN: Retrospective, longitudinal
      cohort assessed at 1, 6, and 12 months postinjury. MAIN MEASURES: Outcomes were 3
      cognitive domains: processing speed/executive function, verbal fluency, and
      memory. Premorbid IQ, estimated with the Wechsler Test of Adult Reading, served
      as CR proxy. RESULTS: Higher premorbid IQ was associated with better performance
      on cognitive domains at 1 month postinjury, and the effect of IQ was similarly
      beneficial for all groups. Cognitive recovery rate was moderated only by TBI
      severity; those with more severe TBI had faster recovery in the first year.
      CONCLUSION: Results support only the neural reserve theory of CR within a TBI
      population and indicate that CR is neuroprotective, regardless of the degree of
      TBI. Higher premorbid CR does not allow for more rapid adaptation and recovery
      from injury.

PMID- 28520678
TI  - Anterior Cruciate Ligament Injury at the Time of Anterior Tibial Spine Fracture
      in Young Patients: An Observational Cohort Study.
AB  - BACKGROUND: Anterior tibial spine fractures (ATSF) in the skeletally immature
      parallel anterior cruciate ligament (ACL) tears in adult patients, yet these
      injuries are generally regarded as mutually exclusive. Biomechanical analysis
      suggests that intrinsic ACL damage occurs during ATSF, and long-term clinical
      studies demonstrate residual anteroposterior knee laxity following ATSF. We aim
      to describe prevalence, demographics, and characteristics of pediatric patients
      who sustained ATSF with concomitant ACL injury. METHODS: We included 129 patients
      with ATSF over a 16-year period. Age, sex, injury mechanism, ATSF type, magnetic
      resonance imaging (MRI) evaluation, treatment modality, ACL injury, and
      concomitant meniscal/chondral injuries were analyzed. Concurrent ACL injury was
      confirmed either from MRI or intraoperatively. RESULTS: Nineteen percent (n=25)
      of ATSF patients had concomitant ACL injury, with ACL injury significantly more
      likely in type II or type III ATSF compared with type I ATSF (P=0.03). Patients
      with combined ATSF/ACL injury were significantly older (P=0.02) and more likely
      to be male (P=0.01). Mechanism of ATSF injury was not associated with ACL injury
      (P=0.83). Preoperative MRI had low sensitivity (0.09) for recognizing ACL injury
      at the time of ATSF relative to intraoperative assessment. Half of ATSF/ACL
      injured patients had additional meniscal or chondral injury, with meniscal repair
      or debridement required in 37.5% of the type II ATSF/ACL injury. CONCLUSIONS:
      There are demographic characteristics, such as age (older) and sex (male),
      associated with a higher risk of concomitant ACL injury at the time of ATSF. Type
      II and type III ATSF patterns had a higher prevalence of ACL injury. MRI failed
      to correctly identify ACL injury at the time of ATSF. Concomitant ACL injury at
      the time of ATSF is highly prevalent in the skeletally immature, occurring in
      19.4% of patients with ATSF. LEVEL OF EVIDENCE: Level IV-case series.

PMID- 28520677
TI  - The Use of an Electrophysiological Brain Function Index in the Evaluation of
      Concussed Athletes.
AB  - OBJECTIVE: To evaluate the effectiveness of the electroencephalographic (EEG)
      Brain Function Index (BFI) for characterizing sports-related concussive injury
      and recovery. PARTICIPANTS: Three hundred fifty-four (354) male contact sport
      high school and college athletes were prospectively recruited from multiple
      locations over 6 academic years of play (244 control baseline athletes and 110
      athletes with a concussion). METHODS: Using 5 to 10 minutes of eyes closed
      resting EEG collected from frontal and frontotemporal regions, a BFI was computed
      for all subjects and sessions. Group comparisons were performed to test for the
      significance of the difference in the BFI score between the controls at baseline
      and athletes with a concussion at several time points. RESULTS: There was no
      significant difference in BFI between athletes with a concussion at baseline (ie,
      prior to injury) and controls at baseline (P = .4634). Athletes with a
      concussion, tested within 72 hours of injury, exhibited significant differences
      in BFI compared with controls (P = .0036). The significant differences in BFI
      were no longer observed at 45 days following injury (P = .19). CONCLUSION:
      Controls and athletes with a concussion exhibited equivalent BFI scores at
      preseason baseline. The concussive injury (measured within 72 hours)
      significantly affected brain function reflected in the BFI in the athletes with a
      concussion. The BFI of the athletes with a concussion returned to levels seen in
      controls by day 45, suggesting recovery. The BFI may provide an important
      objective marker of concussive injury and recovery.

PMID- 28520679
TI  - Knee Recurvatum in Children With Spastic Diplegic Cerebral Palsy.
AB  - BACKGROUND: The purpose of this study is to determine which factors drive
      patients with diplegic cerebral palsy to walk without knee recurvatum despite
      hyperextension of the knee on physical examination. METHODS: A retrospective
      review was conducted of all data collected in the Gait Analysis Laboratory
      between 1999 and 2014. Patients with spastic diplegic cerebral palsy and at least
      5 degrees of knee extension on clinical examination were identified for the
      study. After IRB approval, a total of 60 children ranging in age from 4 to 17
      were included in the study. There were 27 female patients. Gross Motor Function
      Classification System level was distributed in the population as follows: 34
      patients at Gross Motor Function Classification System level I, 18 at level II,
      and 8 at level III. Patients were excluded from this study if they had
      extrapyramidal involvement, history of selective dorsal rhizotomy or lower
      extremity surgery. Patient who received botulinum toxin A injections within 1
      year of the study were excluded as well. Patients were divided into 2 groups:
      children that walked with knee hyperextension (KH) and children that walked
      without knee hyperextension (KF, "knee flexion"). There were 15 subjects in the
      KH group and 45 subjects in the KF group. Motion Laboratory evaluation included a
      comprehensive examination, kinematics, and kinetic analysis with a VICOM system.
      All data were analyzed with unpaired t test to detect differences between the 2
      groups. All statistical analysis was done only for the right legs (unless the
      right leg did not meet the exclusion then the left leg was analyzed) to meet the
      statistical requirement for independence. The Pearson correlation was applied to
      correlate the maximum knee extension in stance with maximum ankle dorsiflexion in
      stance. RESULTS: The static measurement of dorsiflexion with knee flexed showed
      statistically significant difference (P=0.004) with KH group having 2.3+/-11.6
      degrees and KF group having 13.1+/-12.2 degrees. There was also a statistically
      significant difference in the static measurement of dorsiflexion with knee
      extended (P=0.0014) with KH group having -3.3+/-9.0 degrees and KF group having
      5.8+/-9.1 degrees. Maximum dorsiflexion in stance phase also showed significant
      difference (P=0.0022) with the KH group having 0.1+/-14.0 degrees and KF group
      having 11.5+/-11.2 degrees. Maximum dorsiflexion in stance phase also showed
      significant difference (P<0.001) with the DH group having 0.1 (SD) 14.0 degrees
      and KF group having 11.5 (SD) 11.2 degrees. There were no significant differences
      in popliteal angle measurements or any strength measurement. CONCLUSIONS: Our
      study shows that the plantar flexion knee extension couple is the major
      contributing factor to cause patients with passive knee hyperextension to walk in
      a recurvatum pattern. This would have implications of further treatment of the
      knee hyperextension in stance. LEVEL OF EVIDENCE: Level III-case-control study.

PMID- 28520680
TI  - Acute Pediatric Monteggia Fractures: A Conservative Approach to Stabilization.
AB  - BACKGROUND: In 2015, a multicenter study group proposed a treatment algorithm for
      pediatric Monteggia fractures based upon the ulnar fracture pattern. This
      strategy recommends surgical stabilization for all complete ulna fractures. The
      purpose of this study was to evaluate whether an initial nonoperative approach to
      pediatric Monteggia fractures resulted in poorer outcomes and a higher rate of
      complications. METHODS: This institutional review board approved retrospective
      study evaluated all Monteggia fractures presenting to a level 1 pediatric trauma
      center between 2008 and 2014. Chart and radiographic reviews were performed on 94
      patients who met inclusion criteria. The mean age was 5.5 years (range, 1 to 13
      y). The mean clinical follow-up was 18 weeks. Major complications were defined as
      those requiring an unplanned second procedure (other than implant removal) or
      that may result in long-term disability (residual radial head
      subluxation/dislocation). Univariate (P<0.05) and Multivariate Classification and
      Regression Tree (CART) (P<0.05) analyses were used to identify variables
      associated with the need for surgical stabilization. RESULTS: At final follow-up,
      there were no cases of residual radiocapitellar joint subluxation or dislocation
      and all fractures had healed. The majority (83%) of patients were successfully
      managed with a cast. Univariate analysis found Bado type and maximum ulna
      angulation as significant predictors (P<0.05), whereas the CART analysis found
      ulna angulation >36.5 degrees as the only primary predictor of requiring surgical
      stabilization. Overall, good outcomes were achieved in all patients with few
      major complications. CONCLUSIONS: Although treatment algorithms are intended to
      minimize complications and maximize good outcomes, we believe that an
      unintentional consequence of the recently proposed pediatric Monteggia fracture
      treatment guideline may be the overtreatment of these injuries. In our cohort,
      the majority of patients were able to avoid the operating room and surgical
      implants without compromising outcomes or complications. This more conservative
      approach, however, requires close monitoring of patients in the first 3 weeks
      during which most reductions were lost. LEVEL OF EVIDENCE: Level IV-therapeutic
      studies, case series.

PMID- 28520681
TI  - Delayed Dural Leak Following Posterior Spinal Fusion for Idiopathic Scoliosis
      Using All Posterior Pedicle Screw Technique.
AB  - BACKGROUND: In pediatric patients, pedicle screws are malpositioned 5% to 15% of
      the time. Complications associated with malpositioned screws are infrequently
      reported in the literature. We present a series of adolescent idiopathic
      scoliosis (AIS) patients who presented in a delayed manner with positional
      headache and chronic dural leak adjacent to the pedicle screw tract. METHODS:
      Scoliosis databases at 2 centers were reviewed, and cases of delayed positional
      headaches following posterior spinal fusion for AIS were identified. Demographic
      and clinical data were collected. RESULTS: Of 322 patients, 4 patients presented
      with positional headaches at a mean of 12.8 weeks following posterior spinal
      fusion surgery for AIS, with an interval time to diagnosis of 5 months. Computed
      tomographic myelogram demonstrated severe pedicle screw malposition in 1 patient,
      and minimal malposition in 3 patients (<2 mm violation). The patients had delayed
      presentation with positional headaches secondary to dural leak. All patients
      successfully underwent revision surgery with repair of the dural leak. At the
      time of latest follow-up, all patients are asymptomatic. CONCLUSIONS: Pedicle
      screw malposition can result in dural leaks. Patients may present in a delayed
      manner with positional headaches and an acquired Chiari malformation. Clinical
      suspicion should prompt imaging of the brain or cervical spine followed by
      computed tomographic myelogram to determine site of leak. This is a rare
      complication from pedicle screw malposition. LEVELS OF EVIDENCE: Level IV-case
      series.

PMID- 28520683
TI  - Socioeconomic consequences of systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: The present review addresses recent literature investigating
      the socioeconomic consequences of systemic lupus erythematosus (SLE). We
      highlight the latest updates on health disparities affecting the SLE population,
      the direct and indirect economic costs of the disease, and less quantifiable
      costs such as reduced health-related quality of life (HRQoL). RECENT FINDINGS:
      Health disparities continue to exist among socially disadvantaged populations,
      including African Americans, Hispanics, and patients with decreased educational
      attainment and in poverty. Direct and indirect costs are substantial. Recent work
      provides updated cost estimates for patients with SLE outside of North America,
      including those in developing countries. Previous research has largely focused on
      costs of the general SLE population and those with renal manifestations or active
      SLE, whereas recent research addresses special populations such as hospitalized
      and pregnant patients and glucocorticoid users. Patients with SLE and their
      caregivers experience a substantially reduced HRQoL. SUMMARY: SLE is a costly
      disease that disproportionately affects disadvantaged populations. Future
      economic studies should measure not only direct costs, but also incorporate
      indirect costs and the HRQoL of both patients with SLE and their caregivers. All
      these components are essential to provide a comprehensive assessment of the
      socioeconomic consequences of SLE and an appreciation of the potential impact of
      novel therapies.

PMID- 28520682
TI  - Progress in the pathogenesis and treatment of cardiac manifestations of neonatal
      lupus.
AB  - PURPOSE OF REVIEW: To provide new insights into pathogenesis, prevention and
      management of cardiac manifestations of neonatal lupus (cardiac neonatal lupus)
      and issues pertinent to all anti-SSA/Ro positive individuals of childbearing age.
      RECENT FINDINGS: Antibody specificity with high risk for cardiac neonatal lupus
      remains elusive, but high titers of Ro60, Ro52 or Ro52p200 antibodies appear to
      be required. Varying antibody specificities to the p200 region of Ro52 can induce
      first-degree block in a rodent model. In consideration of the contribution of
      macrophages to inflammation and fibrosis in cardiac neonatal lupus,
      hydroxychloroquine (HCQ) is being considered as preventive therapy. Cord blood
      biomarkers support the association of fetal reactive inflammatory and fibrotic
      components with the development and morbidity of cardiac neonatal lupus. Data
      from U.S. and French registries do not provide evidence that the prompt use of
      fluorinated steroids in cases of isolated block significantly alters
      fetal/neonatal morbidity or mortality. SUMMARY: The search for a high-risk
      cardiac neonatal lupus antibody profile remains, but high-titer antibodies to
      Ro60 and R052 are a consistent finding, and this may guide the need for fetal
      echocardiographic surveillance. The uniform use of fluorinated steroids to
      prevent progression of cardiac neonatal lupus or reduce mortality does not appear
      justified. HCQ, based on diminishing an inflammatory component of cardiac
      neonatal lupus, is under consideration as a potential preventive approach.

PMID- 28520684
TI  - Pediatric trauma undertriage in Ohio.
AB  - BACKGROUND: Appropriate and timely triage is an essential component of a trauma
      system. In the state of Ohio, there are 6 verified pediatric trauma centers
      (PTCs) across 8 state regions. The purpose of this study was to better understand
      the pediatric undertriage rates in the state. METHODS: We used the Ohio Trauma
      Registry from 2007 to 2012, consisting of 14,045 records of children younger than
      16 years admitted to a hospital for more than 48 hours or who sustained a
      traumatic death. Pediatric undertriage was defined as not being directly
      transported to a PTC when one was available within 30 minutes or not being
      transferred to a PTC within 2 hours of injury. RESULTS: The state pediatric
      undertriage rate was 52%, only decreasing to 35% when up to a 4-hour transfer
      time was allowed. Across state trauma regions, undertriage rates varied from 94%
      to 40%. More than 28% of injured children had access to a PTC within 30 minutes
      of their home. A trauma center (adult or pediatric) was within 30 minutes for 66%
      of the children, yet 32% of the children went to a nontrauma center first.
      Overall, 29% of children never made it to a PTC, and 4% of children remained at a
      nontrauma center, with regional variation from 5% to 0.5%. Statewide mortality
      was nearly 3%, with regional variations between 5% and 0.4%. Mortality rate
      within the appropriately triaged group was 5.3%, while mortality rate in the
      undertriage group was only 0.7%. Overall, 53% of transferred patients had a more
      than 2-hour transfer time. CONCLUSIONS: Despite the significant number of PTCs in
      Ohio, there remains a high undertriage rate with significant regional variations
      and long transfer times. Continued analysis will be useful in furthering trauma
      system development for the injured child. LEVEL OF EVIDENCE: Therapeutic/care
      management study, level IV; epidemiological, level IV.

PMID- 28520685
TI  - Pelvic fracture pattern predicts the need for hemorrhage control intervention
      Results of an AAST multi-institutional study.
AB  - BACKGROUND: Early identification of patients with pelvic fractures at risk of
      severe bleeding requiring intervention is critical. We performed a multi
      institutional study to test our hypothesis that pelvic fracture patterns predict
      the need for a pelvic hemorrhage control intervention. METHODS: This prospective,
      observational, multicenter study enrolled patients with pelvic fracture due to
      blunt trauma. Inclusion criteria included shock on admission (systolic blood
      pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the
      ability to review pelvic imaging). Demographic data, open pelvic fracture, blood
      transfusion, pelvic hemorrhage control intervention (angioembolization, external
      fixator, pelvic packing, and/or REBOA [resuscitative balloon occlusion of the
      aorta]), and mortality were recorded. Pelvic fracture pattern was classified
      according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage
      control intervention and mortality were analyzed by univariate and multivariate
      regression analyses. RESULTS: A total of 163 patients presenting in shock were
      enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern
      was lateral compression I, followed by lateral compression I, and vertical shear.
      Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%)
      required a pelvic hemorrhage control intervention. Factors associated with the
      need for pelvic fracture hemorrhage control intervention on univariate analysis
      included vertical shear pelvic fracture pattern, increasing age, and transfusion
      of blood products. Anterior-posterior compression III fracture patterns and open
      pelvic fracture predicted the need for pelvic hemorrhage control intervention on
      multivariate analysis. Overall in-hospital mortality for patients admitted in
      shock with pelvic fracture was 30% and did not differ based on pelvic fracture
      pattern on multivariate analysis. CONCLUSION: Blunt trauma patients admitted in
      shock with anterior-posterior compression III fracture patterns or patients with
      open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage
      control intervention. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level
      III.

PMID- 28520686
TI  - Clinical correlates to assist with chronic traumatic encephalopathy diagnosis:
      Insights from a novel rodent repeat concussion model.
AB  - INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a neurodegenerative
      disease linked to repetitive head injuries. Chronic traumatic encephalopathy
      symptoms include changes in mood, behavior, cognition, and motor function;
      however, CTE is currently diagnosed only postmortem. Using a rat model of
      recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that
      predict the severity of CTE-like brain pathology. METHODS: Bilateral, closed
      skull, mild TBI was administered once per week to 35 wild-type rats; eight rats
      received two injuries (2*TBI), 27 rats received five injuries (5*TBI), and 13
      rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI
      rats were separated based on the severity of rotarod deficits and classified as
      "mild" or "severe" and further separated into "acute," "short," and "long" based
      on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy,
      phosphorylated tau, and inflammation were assessed. RESULTS: All eight 2*TBI
      cases had mild rotarod deficiency, 11 5*TBI cases had mild deficiency, and 16
      cases had severe deficiency. In one cohort of rats, tested at approximately 235
      days of age, balance, rearing, and grip strength were significantly worse in the
      severe group relative to both sham and mild groups. At the acute time period,
      cortical thinning, phosphorylated tau, and inflammation were not observed in
      either TBI group, whereas corpus callosum thinning was observed in both TBI
      groups. At later time points, atrophy, tau pathology, and inflammation were
      increased in mild and severe TBI groups in the cortex and corpus callosum,
      relative to sham controls. These injury effects were exacerbated over time in the
      severe TBI group in the corpus callosum. CONCLUSIONS: Our model of repeat mild
      TBI suggests that permanent deficits in specific motor function tests correlate
      with CTE-like brain pathology. Assessing balance and motor coordination over time
      may predict CTE diagnosis.

PMID- 28520687
TI  - 3% NaCl adenosine, lidocaine, Mg2+ (ALM) bolus and 4 hours "drip" infusion
      reduces noncompressible hemorrhage by 60% in a rat model.
AB  - BACKGROUND: Noncompressible torso hemorrhage is the leading cause of potentially
      survivable trauma in far-forward combat environments. Our aim was to examine the
      effect of small-volume 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 0.9%
      NaCl/ALM "drip" on survivability and cardiac/gut/kidney function in a rat model
      of hepatic hemorrhage and shock. METHODS: Male Sprague-Dawley rats (428 +/- 4 g)
      were anesthetized and randomly assigned to one of five groups (n = 16): (1) Sham,
      (2) No treatment, (3) Saline controls, (4) ALM therapy, and (5) Hextend. Animals
      were ventilated, instrumented with single or double laparotomy for tissue probe
      insertion, and hemorrhage induced by liver resection. After 15 minutes, a single
      3% NaCl +/- ALM bolus (0.7 ml/kg) was injected IV (phase 1) and after 60 minutes,
      4 hours 0.9% NaCl +/- ALM stabilization "drip" (0.5 ml/kg/h) was administered
      (phase 2), with 1-hour monitoring. RESULTS: Mortality for Shams (no resection)
      was 0% (25%); No treatment, 87.5% (100%); Saline controls, 37.5% (75%); ALM
      therapy, 0% (25%), and Hextend, 87.5% (100%) (double laparotomy in parentheses).
      Hextend-treated animals died during the first 20 minutes of phase 2. A single ALM
      bolus during phase 1 led to a 2.4-fold higher cardiac output and improved
      hemodynamics. 3% NaCl ALM bolus increased tissue pO2 and flow in gut and kidney
      during phase 1 and, during ALM "drip" in phase 2, tissue pO2 decreased but flow
      continued to rise, indicating increased tissue O2 extraction and delivery. During
      phase 2, CO, ejection fraction, and fractional shortening decreased and were
      erratic in all groups except ALM treatment. ALM therapy led to up to 60% less
      bleeding over 6 hours compared to Saline controls and 75% less bleeding than
      Hextend. CONCLUSIONS: Small-volume ALM therapy significantly reduced mortality
      and internal bleeding compared to Saline controls or Hextend-treated rats.
      Hextend increased mortality, severe bleeding, and microvascular-organ injury.

PMID- 28520688
TI  - The association of nonaccidental trauma with historical factors, examination
      findings, and diagnostic testing during the initial trauma evaluation.

PMID- 28520689
TI  - The course, prediction, and treatment of acute and posttraumatic stress in trauma
      patients: A systematic review.
AB  - BACKGROUND: Trauma patients suffer from acute stress disorder (ASD) and
      posttraumatic stress disorder (PTSD), but it is unknown how these disorders
      develop over time and when treatment is effective. Our aim was to systematically
      review (1) the course and predictors of ASD and PTSD after trauma and (2) which
      and when psychological treatments are effective. METHODS: Embase, Medline, Web of
      Science, Scopus, PsycInfo, Cinahl, Cochrane, PubMed, and Google Scholar were
      searched up to September 14, 2015. Quality was assessed with STROBE and CONSORT
      checklists. RESULTS: Overall, 45 (68%) observational studies and 21 (32%)
      intervention studies were included. Forty-seven (85%) were of lower (level of
      evidence (LoE) 3) or poor quality (LoE 4). ASD was found during hospitalization
      (range 1-37%) and about 30% experienced PTSD 1 month after trauma (LoE 3). The
      onset of PTSD was within 3 months but also up to 12 months after trauma (LoE 3).
      Especially in patients with ASD, patients showed PTSD symptoms after 6 years (LoE
      3). ASD and PTSD were associated with sociodemographic factors (e.g., being
      female, younger age, financial problems, and low income), reduced cognitive
      functioning, and physical (e.g., pain), social (e.g., low social support), and
      psychological problems (e.g., hyperarousal) or disorders (e.g., ASD). Early
      treatment in the first weeks after trauma can be preventive for PTSD, but
      effective treatment for ASD is still unclear. Compared to other psychological
      treatments, the most effective and examined treatment for PTSD was cognitive
      behavioral therapy (CBT). CONCLUSIONS: A large number of studies of lower or poor
      quality present inconsistent findings on the course of ASD and PTSD. Predictors
      for ASD and PTSD were identified. Early treatment can be preventive for PTSD, as
      CBT is the most effective treatment. However, good qualitative observational and
      intervention studies are lacking and needed. LEVEL OF EVIDENCE: Systematic
      review, level III.

PMID- 28520690
TI  - Managing grade 5 pancreatic injuries-Think smart, act smart, and call in the
      pancreatic cavalry early.

PMID- 28520692
TI  - Featured Articles for CME Credit June 2017.

PMID- 28520691
TI  - Re: Managing grade V pancreatic injuries-Think smart, act smart, and call in the
      pancreatic cavalry early.

PMID- 28520694
TI  - Metabolic Inflammatory Complex in Sepsis: Septic Cachexia as a Novel Potential
      Therapeutic Target.
AB  - Despite several decades of focused investigation, sepsis remains a major cause of
      mortality in critically ill patients. Advancements in intensive care have enabled
      more patients to survive the acute phase of sepsis than previously, but a growing
      number of them progress to chronic critical illness. The failure of previous
      randomized clinical trials of anti-inflammatory agents to show any pro-survival
      benefit in septic patients underscores current thought that simple anti
      inflammatory strategies are ineffective because the inhibitory effect of anti
      inflammatory agents undermines the immune response to pathogens. New strategies
      with the dual capability of ameliorating inflammation in organs while stimulating
      antimicrobial activity are eagerly awaited. On the other hand, the metabolic
      alterations associated with systemic inflammatory response, including
      mitochondrial dysfunction and metabolic shift, are closely linked through a nexus
      of signaling pathways and signaling molecules. Preventing these metabolic
      derangements may be an alternative way to control excessive inflammation, an
      intriguing possibility that has not been fully explored. New insight into the
      molecular pathogenesis of sepsis and sepsis-associated chronic critical illness
      has led to the recognition of septic cachexia, a life-threatening form of
      metabolic inflammatory complex associated with multiple organ dysfunction. The
      potential for septic cachexia to serve as a novel target disease state to improve
      the clinical outcome of septic patients is discussed in this review.

PMID- 28520695
TI  - Calreticulin Ameliorates Hypoxia/Reoxygenation-Induced Human Microvascular
      Endothelial Cell Injury By Inhibiting Autophagy.
AB  - BACKGROUND: Autophagy has been found to be involved in myocardial
      ischemia/reperfusion injury. However, the underlying mechanism and significance
      of autophagy in reperfusion injury remain unclear. Herein, we evaluated the
      effects of exogenous calreticulin (CRT) on autophagy in hypoxia/reoxygenation
      (H/R)-treated human microvascular endothelial cells (MECs). METHODS: Human MECs
      were pretreated with CRT (25 pg/mL) for 30 min, followed by exposure in an
      incubator filled with a gas mixture of 90% N2, 5% O2, and 5% CO2 for 8-h hypoxia.
      The cells were then placed back in the normoxic CO2 incubator for 16-h
      reoxygenation. Cell injury was assessed by the cell counting kit-8 assay.
      Autophagosomes were detected by transmission electron microscopy and
      immunofluorescence staining. Western blot analysis was performed to detect
      phosphorylated mammalian target of rapamycin (p-mTOR), Beclin 1, and microtubule
      associated protein 1 light chain 3 (LC3). RESULTS: H/R induced marked autophagy
      through the mTOR pathway. CRT suppressed rapamycin- and H/R-induced autophagosome
      formation, the LC3-II/LC3-I ratio, and Beclin 1 expression in human MECs by
      upregulating mTOR phosphorylation, consequently attenuating H/R-induced human MEC
      injury. CONCLUSIONS: Exogenous CRT attenuated H/R-induced human MEC injury by
      inhibiting autophagy.

PMID- 28520697
TI  - Prescription drug prices in the US.

PMID- 28520696
TI  - An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.
AB  - BACKGROUND: Animal models of endotoxemia are frequently used to understand the
      pathophysiology of sepsis and test new therapies. However, important differences
      exist between commonly used experimental models of endotoxemia and clinical
      sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in
      contrast to clinical hyperdynamic shock. This difference may exaggerate the
      importance of hypoperfusion as a causative factor in organ dysfunction. This
      study sought to develop an ovine model of hyperdynamic endotoxemia and assess if
      there is evidence of impaired oxidative metabolism in the vital organs. METHODS:
      Eight sheep had microdialysis catheters implanted into the brain, heart, liver,
      kidney, and arterial circulation. Shock was induced with a 4 h escalating dose
      infusion of endotoxin. After 3 h vasopressor support was initiated with
      noradrenaline and vasopressin. Animals were monitored for 12 h after endotoxemia.
      Blood samples were recovered for hemoglobin, white blood cell count, creatinine,
      and proinflammatory cytokines (IL-1Beta, IL-6, and IL-8). RESULTS: The endotoxin
      infusion was successful in producing distributive shock with the mean arterial
      pressure decreasing from 84.5 +/- 12.8 mm Hg to 49 +/- 8.03 mm Hg (P < 0.001).
      Cardiac index remained within the normal range decreasing from 3.33 +/- 0.56
      L/min/m to 2.89l +/- 0.36 L/min/m (P = 0.0845). Lactate/pyruvate ratios were not
      significantly abnormal in the heart, brain, kidney, or arterial circulation.
      Liver microdialysis samples demonstrated persistently high lactate/pyruvate
      ratios (mean 37.9 +/- 3.3). CONCLUSIONS: An escalating dose endotoxin infusion
      was successful in producing hyperdynamic shock. There was evidence of impaired
      oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This
      may be a modifiable factor in the progression to multiple organ dysfunction and
      death.

PMID- 28520698
TI  - Valbenazine (Ingrezza) for tardive dyskinesia.

PMID- 28520699
TI  - Oxymetazoline cream (Rhofade) for rosacea.

PMID- 28520700
TI  - FDA warns against use of codeine and tramadol in children and breastfeeding
      women.

PMID- 28520701
TI  - Another subcutaneous immune globulin (Cuvitru) for primary immunodeficiency.

PMID- 28520702
TI  - Vonvendi--recombinant von Willebrand factor.

PMID- 28520703
TI  - Comparison table: some topical drugs for rosacea.

PMID- 28520704
TI  - Adverse Events Associated with Treatment of Multidrug-Resistant Tuberculosis in
      China: An Ambispective Cohort Study.
AB  - BACKGROUND Adverse events are under-appreciated negative consequences that are
      significant clinical problems for patients undergoing anti-MDR-TB treatment due
      to longer duration of treatment and more need for concurrent use of multiple
      second-line drugs. The aim of this study was to determine the incidence of
      adverse events and their impact on MDR-TB therapy and treatment outcome, and to
      identify possible drug-event pairs in China. MATERIAL AND METHODS An ambispective
      cohort study was conducted based on hospital medical records, which included a
      retrospective study that enrolled 751 MDR-TB patients receiving standardized
      regimen between May 2009 and July 2013, and a follow-up investigation of
      treatment outcome conducted in December 2016 in China. Adverse events were
      determined according to laboratory results or clinical criteria. Cox's
      proportional hazards regression models were used for evaluating associations.
      RESULTS There were 681(90.7%) patients experienced at least 1 type of adverse
      event and 55.2% of them required a changed MDR-TB treatment; 51(6.8%) patients
      required permanent discontinuation of the offending drug due to adverse events.
      The occurrence of adverse events was associated with poor treatment outcome
      (adjusted hazard ratio, 1.54; 95% CI 1.21, 1.87). A total of 10 different drug
      event pairs were identified. CONCLUSIONS Adverse events occurred commonly during
      MDR-TB treatment in China, and often resulted in MDR-TB treatment change. The
      occurrence of adverse events affected MDR-TB poor outcome after treatment.

PMID- 28520706
TI  - QuickStats: Percentage* of Adults Aged >=65 Years Who Saw Selected Types of
      Health Professionals? in the Past 12 Months, by Diagnosed Diabetes StatusS -
      National Health Interview Survey, 2015.
AB  - In 2015, adults aged >=65 years with diagnosed diabetes were more likely than
      adults without diagnosed diabetes to report seeing general doctors (92.3%
      compared with 86.7%); eye doctors (66.9% compared with 56.6%); physician
      specialists (51.5% compared with 45.5%); foot doctors (29.9% compared with 13.0%)
      and mental health professionals (6.3% compared with 4.5%) in the past 12 months.
      Those with diabetes were less likely than those without diabetes to report seeing
      a dentist or dental hygienist in the past 12 months (54.5% compared with 65.0%).

PMID- 28520705
TI  - Disparities in Diabetes Deaths Among Children and Adolescents - United States,
      2000-2014.
AB  - Diabetes is a common chronic disease of childhood affecting approximately 200,000
      children and adolescents in the United States (1). Children and adolescents with
      diabetes are at increased risk for death from acute complications of diabetes,
      including hypoglycemia and diabetic ketoacidosis (2,3); in 2012, CDC reported
      that during 1968-2009, diabetes mortality among U.S. persons aged <=19 years
      declined by 61% (4). CDC observed disparities by race during 1979-2004, with
      black children and adolescents dying from diabetes at twice the rate of white
      children and adolescents (5). However, no previous study has examined Hispanic
      ethnicity. CDC analyzed data from the National Vital Statistics System for deaths
      among persons aged 1-19 years in the United States during 2000-2014, with
      diabetes listed as the underlying cause of death overall, and for Hispanic, non
      Hispanic white (white), and non-Hispanic black (black) children and adolescents.
      During 2012-2014, black children and adolescents had the highest diabetes death
      rate (2.04 per 1 million population), followed by whites (0.92) and Hispanics
      (0.61). There were no statistically significant changes in diabetes death rates
      over the study period, but disparities persisted among racial/ethnic groups.
      Death from diabetes in children and adolescents is potentially preventable
      through increased awareness of diabetes symptoms (including symptoms of low blood
      sugar), earlier treatment and education related to diabetes, and management of
      diabetes ketoacidosis. Continued measures are needed to reduce diabetes mortality
      in children and understand the cause of racial and ethnic disparities.

PMID- 28520707
TI  - Using Molecular Characterization to Support Investigations of Aquatic Facility
      Associated Outbreaks of Cryptosporidiosis - Alabama, Arizona, and Ohio, 2016.
AB  - Cryptosporidiosis is a nationally notifiable gastrointestinal illness caused by
      parasitic protozoa of the genus Cryptosporidium, which can cause profuse, watery
      diarrhea that can last up to 2-3 weeks in immunocompetent patients and can lead
      to life-threatening wasting and malabsorption in immunocompromised patients.
      Fecal-oral transmission of Cryptosporidium oocysts, the parasite's infectious
      life stage, occurs via ingestion of contaminated recreational water, drinking
      water, or food, or following contact with infected persons or animals,
      particularly preweaned bovine calves (1). The typical incubation period is 2-10
      days. Since 2004, the annual incidence of nationally notified cryptosporidiosis
      has risen approximately threefold in the United States (1). Cryptosporidium also
      has emerged as the leading etiology of nationally notified recreational water
      associated outbreaks, particularly those associated with aquatic facilities
      (i.e., physical places that contain one or more aquatic venues [e.g., pools] and
      support infrastructure) (2). As of February 24, 2017, a total of 13 (54%) of 24
      states reporting provisional data detected at least 32 aquatic facility
      associated cryptosporidiosis outbreaks in 2016. In comparison, 20 such outbreaks
      were voluntarily reported to CDC via the National Outbreak Reporting System for
      2011, 16 for 2012, 13 for 2013, and 16 for 2014. This report highlights
      cryptosporidiosis outbreaks associated with aquatic facilities in three states
      (Alabama, Arizona, and Ohio) in 2016. This report also illustrates the use of
      CryptoNet, the first U.S. molecularly based surveillance system for a parasitic
      disease, to further elucidate Cryptosporidium chains of transmission and
      cryptosporidiosis epidemiology. CryptoNet data can be used to optimize evidence
      based prevention strategies. Not swimming when ill with diarrhea is key to
      preventing and controlling aquatic facility-associated cryptosporidiosis
      outbreaks (https://www.cdc.gov/healthywater/swimming/swimmers/steps-healthy
      swimming.html).

PMID- 28520708
TI  - Hepatitis B Surface Antigen Screening Among Pregnant Women and Care of Infants of
      Hepatitis B Surface Antigen-Positive Mothers - Guam, 2014.
AB  - Hepatitis B virus (HBV) infection is endemic among adults in the U.S. territory
      of Guam (1,2). Perinatal HBV transmission, which occurs at birth from an infected
      mother to her newborn infant, is a major mode of HBV transmission and maintains
      HBV endemicity (3). Approximately 90% of HBV-infected infants will develop
      chronic HBV infection, and approximately 25% of those will die prematurely from
      liver failure or hepatocellular carcinoma (4,5). Since 1988, the Advisory
      Committee on Immunization Practices has recommended that all pregnant women be
      screened for hepatitis B surface antigen (HBsAg), an indicator of HBV infection,
      and that infants of women who screen positive (HBsAg-positive women) receive
      postexposure prophylaxis (PEP) (hepatitis B vaccine and hepatitis B
      immunoglobulin [HBIG]). When received within 12 hours of birth, PEP is 85%-95%
      effective in preventing perinatal HBV transmission (5,6). Hepatitis B vaccine
      provides long-term active immunity to HBV infection and HBIG provides short-term
      passive immunity to HBV infection until the infant responds to the vaccine (5).
      Hepatitis B vaccine was introduced into the routine universal infant vaccination
      schedule in Guam in 1988 (1).

PMID- 28520709
TI  - Updated Recommendations for Use of MenB-FHbp Serogroup B Meningococcal Vaccine -
      Advisory Committee on Immunization Practices, 2016.
AB  - Two serogroup B meningococcal (MenB) vaccines are currently licensed for use in
      persons aged 10-25 years in the United States. The two vaccines are MenB-FHbp
      (Trumenba, Pfizer, Inc.) (1) and MenB-4C (Bexsero, GlaxoSmithKline Biologicals,
      Inc.) (2). In February 2015, the Advisory Committee on Immunization Practices
      (ACIP) recommended use of MenB vaccines among certain groups of persons aged >=10
      years who are at increased risk for serogroup B meningococcal disease* (Category
      A) (3), and in June 2015, ACIP recommended that adolescents and young adults aged
      16-23 years may be vaccinated with MenB vaccines to provide short-term protection
      against most strains of serogroup B meningococcal disease (Category B?) (4).
      Consistent with the original Food and Drug Administration (FDA) licensure for the
      two available MenB vaccines, ACIP recommended either a 3-dose series of MenB-FHbp
      or a 2-dose series of MenB-4C. Either MenB vaccine can be used when indicated;
      ACIP does not state a product preference. The two MenB vaccines are not
      interchangeable; the same vaccine product must be used for all doses in a series.
      In April 2016, changes to the dosage and administration of MenB-FHbp were
      approved by FDA to allow for both a 2-dose series (administered at 0 and 6
      months) and a 3-dose series (administered at 0, 1-2, and 6 months) (5,6). In
      addition, the package insert now states that the choice of dosing schedule
      depends on the patient's risk for exposure and susceptibility to serogroup B
      meningococcal disease. These recommendations are regarding use of the 2- and 3
      dose schedules of MenB-FHbp vaccine (Trumenba) and replace previous ACIP
      recommendations for use of MenB-FHbp vaccine published in 2015 (3,4).
      Recommendations regarding use of MenB-4C (Bexsero) are unchanged (3,4).

PMID- 28520710
TI  - Notes from the Field: Ongoing Transmission of Candida auris in Health Care
      Facilities - United States, June 2016-May 2017.

PMID- 28520711
TI  - Inhalational Chlorine Injuries at Public Aquatic Venues - California, 2008-2015.
AB  - In June 2015, personnel from California's Contra Costa Health Services
      Environmental Health and Hazardous Materials (hazmat) divisions were alerted to a
      possible chemical release at a swimming pool in an outdoor municipal water park.
      Approximately 50 bathers were in the pool when symptoms began; 34 (68%)
      experienced vomiting, coughing, or eye irritation. Among these persons, 17 (50%)
      were treated at the scene by Contra Costa's Emergency Medical Services (EMS) and
      released, and 17 (50%) were transported to local emergency departments; five
      patients also were evaluated later at an emergency department or by a primary
      medical provider. Environmental staff members determined that a chemical
      controller malfunction had allowed sodium hypochlorite and muriatic acid
      (hydrochloric acid) solutions to be injected into the main pool recirculation
      line while the recirculation pump was off; when the main recirculation pump was
      restarted, toxic chlorine gas (generated by the reaction of concentrated sodium
      hypochlorite and muriatic acid) was released into the pool. A review of 2008-2015
      California pesticide exposure records identified eight additional such instances
      of toxic chlorine gas releases at public aquatic venues caused by equipment
      failure or human error that sickened 156 persons. Chemical exposures at public
      aquatic venues can be prevented by proper handling, storage, and monitoring of
      pool chemicals; appropriate equipment operation and maintenance; training of pool
      operators and staff members on pool chemical safety; and reporting of chemical
      exposures.

PMID- 28520712
TI  - Announcement: World IBD Day - May 19, 2017.
AB  - World IBD Day is recognized on May 19 to raise awareness of inflammatory bowel
      disease (IBD) and the two conditions that comprise it: Crohn's disease and
      ulcerative colitis, both of which cause chronic inflammation of the
      gastrointestinal tract. World IBD Day is sponsored by the European Federation of
      Crohn's and Ulcerative Colitis Associations, which includes the Crohn's & Colitis
      Foundation.

PMID- 28520714
TI  - Alteration of stream temperature by natural and artificial beaver dams.
AB  - Beaver are an integral component of hydrologic, geomorphic, and biotic processes
      within North American stream systems, and their propensity to build dams alters
      stream and riparian structure and function to the benefit of many aquatic and
      terrestrial species. Recognizing this, beaver relocation efforts and/or
      application of structures designed to mimic the function of beaver dams are
      increasingly being utilized as effective and cost-efficient stream and riparian
      restoration approaches. Despite these verities, the notion that beaver dams
      negatively impact stream habitat remains common, specifically the assumption that
      beaver dams increase stream temperatures during summer to the detriment of
      sensitive biota such as salmonids. In this study, we tracked beaver dam
      distributions and monitored water temperature throughout 34 km of stream for an
      eight-year period between 2007 and 2014. During this time the number of natural
      beaver dams within the study area increased by an order of magnitude, and an
      additional 4 km of stream were subject to a restoration manipulation that
      included installing a high-density of Beaver Dam Analog (BDA) structures designed
      to mimic the function of natural beaver dams. Our observations reveal several
      mechanisms by which beaver dam development may influence stream temperature
      regimes; including longitudinal buffering of diel summer temperature extrema at
      the reach scale due to increased surface water storage, and creation of cool
      water channel scale temperature refugia through enhanced groundwater-surface
      water connectivity. Our results suggest that creation of natural and/or
      artificial beaver dams could be used to mitigate the impact of human induced
      thermal degradation that may threaten sensitive species.

PMID- 28520713
TI  - Combining inferred regulatory and reconstructed metabolic networks enhances
      phenotype prediction in yeast.
AB  - Gene regulatory and metabolic network models have been used successfully in many
      organisms, but inherent differences between them make networks difficult to
      integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial
      solution, but it does not incorporate network inference and underperforms in
      eukaryotes. We present an Integrated Deduced And Metabolism (IDREAM) method that
      combines statistically inferred Environment and Gene Regulatory Influence Network
      (EGRIN) models with the PROM framework to create enhanced metabolic-regulatory
      network models. We used IDREAM to predict phenotypes and genetic interactions
      between transcription factors and genes encoding metabolic activities in the
      eukaryote, Saccharomyces cerevisiae. IDREAM models contain many fewer
      interactions than PROM and yet produce significantly more accurate growth
      predictions. IDREAM consistently outperformed PROM using any of three popular
      yeast metabolic models and across three experimental growth conditions.
      Importantly, IDREAM's enhanced accuracy makes it possible to identify subtle
      synthetic growth defects. With experimental validation, these novel genetic
      interactions involving the pyruvate dehydrogenase complex suggested a new role
      for fatty acid-responsive factor Oaf1 in regulating acetyl-CoA production in
      glucose grown cells.

PMID- 28520715
TI  - Geographical distribution of complement receptor type 1 variants and their
      associated disease risk.
AB  - BACKGROUND: Pathogens exert selective pressure which may lead to substantial
      changes in host immune responses. The human complement receptor type 1 (CR1) is
      an innate immune recognition glycoprotein that regulates the activation of the
      complement pathway and removes opsonized immune complexes. CR1 genetic variants
      in exon 29 have been associated with expression levels, C1q or C3b binding and
      increased susceptibility to several infectious diseases. Five distinct CR1
      nucleotide substitutions determine the Knops blood group phenotypes, namely
      Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-. METHODS: CR1 variants were genotyped
      by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam,
      India, Republic of Congo and Ghana. RESULTS: The distribution of the CR1 alleles,
      genotypes and haplotypes differed significantly among geographical settings
      (p<=0.001). CR1 variants rs17047660A/G (McCa/b) and rs17047661A/G (Sl1/Sl2) were
      exclusively observed to be polymorphic in African populations compared to the
      groups from Asia and South-America, strongly suggesting that these two SNPs may
      be subjected to selection. This is further substantiated by a high linkage
      disequilibrium between the two variants in the Congolese and Ghanaian
      populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA
      haplotype was found more frequently among the Brazilian and Vietnamese study
      groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese
      populations, while the CR1*AGAGTG haplotype was frequent among Congolese and
      Ghanaian individuals. CONCLUSION: The African populations included in this study
      might have a selective advantage conferred to immune genes involved in pathogen
      recognition and signaling, possibly contributing to disease susceptibility or
      resistance.

PMID- 28520717
TI  - Modular Protein Expression Toolbox (MoPET), a standardized assembly system for
      defined expression constructs and expression optimization libraries.
AB  - The design and generation of an optimal expression construct is the first and
      essential step in in the characterization of a protein of interest. Besides
      evaluation and optimization of process parameters (e.g. selection of the best
      expression host or cell line and optimal induction conditions and time points),
      the design of the expression construct itself has a major impact. However, the
      path to this final expression construct is often not straight forward and
      includes multiple learning cycles accompanied by design variations and retesting
      of construct variants, since multiple, functional DNA sequences of the expression
      vector backbone, either coding or non-coding, can have a major impact on
      expression yields. To streamline the generation of defined expression constructs
      of otherwise difficult to express proteins, the Modular Protein Expression
      Toolbox (MoPET) has been developed. This cloning platform allows highly efficient
      DNA assembly of pre-defined, standardized functional DNA modules with a minimal
      cloning burden. Combining these features with a standardized cloning strategy
      facilitates the identification of optimized DNA expression constructs in shorter
      time. The MoPET system currently consists of 53 defined DNA modules divided into
      eight functional classes and can be flexibly expanded. However, already with the
      initial set of modules, 792,000 different constructs can be rationally designed
      and assembled. Furthermore, this starting set was used to generate small and mid
      sized combinatorial expression optimization libraries. Applying this screening
      approach, variants with up to 60-fold expression improvement have been identified
      by MoPET variant library screening.

PMID- 28520716
TI  - Expected population weight and diabetes impact of the 1-peso-per-litre tax to
      sugar sweetened beverages in Mexico.
AB  - STUDY QUESTION: What effect on body mass index, obesity and diabetes can we
      expect from the 1-peso-per-litre tax to sugar sweetened beverages in Mexico?
      METHODS: Using recently published estimates of the reductions in beverage
      purchases due to the tax, we modelled its expected long-term impacts on body mass
      index (BMI), obesity and diabetes. Microsimulations based on a nationally
      representative dataset were used to estimate the impact of the tax on BMI and
      obesity. A Markov population model, built upon an age-period-cohort model of
      diabetes incidence, was used to estimate the impact on diagnosed diabetes in
      Mexico. To analyse the potential of tax increases we also modelled a 2-peso-per
      litre tax scenario. STUDY ANSWER AND LIMITATIONS: Ten years after the
      implementation of the tax, we expect an average reduction of 0.15 kg/m2 per
      person, which translates into a 2.54% reduction in obesity prevalence. People in
      the lowest level of socioeconomic status and those between 20 and 35 years of age
      showed the largest reductions in BMI and overweight and obesity prevalence.
      Simulations show that by 2030, under the current implementation of 1-peso-per
      litre, the tax would prevent 86 to 134 thousand cases of diabetes. Overall, the 2
      peso-per-litre scenario is expected to produce twice as much of a reduction.
      These estimates assume the tax effect on consumption remains stable over time.
      Sensitivity analyses were conducted to assess the robustness of findings; similar
      results were obtained with various parameter assumptions and alternative
      modelling approaches. WHAT THIS STUDY ADDS: The sugar-sweetened beverages tax in
      Mexico is expected to produce sizable and sustained reductions in obesity and
      diabetes. Increasing the tax could produce larger benefits. While encouraging,
      estimates will need to be updated once data on direct changes in consumption
      becomes available.

PMID- 28520718
TI  - Retrospective observational evaluation of postoperative oxygen saturation levels
      and associated postoperative respiratory complications and hospital resource
      utilization.
AB  - INTRODUCTION: The clinical importance of postoperative episodic hypoxemia is
      still unclear, and therefore largely under-studied. As a result, there is limited
      understanding of its relationship with early postoperative respiratory
      complications (PRC, defined as intubation within three days of surgery) and
      hospital resource utilization. MATERIALS AND METHODS: This single center study
      was performed using a retrospective observational design. We described population
      based definitions of desaturation from continuous SpO2 monitoring data captured
      in the post anesthesia care unit (PACU), namely median SpO2 in PACU, duration of
      desaturation below median, nadir desaturation, and length of oxygen therapy
      relative to PACU duration. These measures were evaluated against the occurrence
      of early PRC in logistic regression models. Measures that were independently
      associated with early PRC were accepted as the primary study exposures.
      Stratified logistic regression models were planned if significant interaction
      occurred with high risk surgical procedures. Models were adjusted by including
      several patient conditions, procedural, and anesthesia risk factors. Propensity
      matching on desaturation occurrence was planned to evaluate the relationship with
      postoperative resource utilization. RESULTS: Among 125,740 patients included in
      the univariate analyses, 351 patients (0.3%) developed early PRC. Nadir
      desaturation <89% [14.3% of patients; adjusted odds ratio 2.02; 95% CI 1.52,
      2.68; p<0.001] and PACU oxygen therapy requirements greater than 60 min [adjusted
      odds ratio 1.92 (>60 min) to 3.04 (>90 min); p<0.001] were identified as
      independent predictors of early PRC occurrence. A modest interaction was observed
      between desaturation and higher surgical risk. Propensity matching for
      postoperative oxygen requirement was performed in 37,354 matched patients.
      Matched analysis demonstrated significant increase in day of surgery charges,
      respiratory charges, total charges, hospital length of stay, reintubation and use
      of invasive or non-invasive ventilatory support. CONCLUSIONS: In summary, we
      report that prolonged PACU oxygen therapy and nadir desaturation <89% in PACU as
      captured in a retrospective database are independently associated with early PRC.
      This study describes resource implications of PACU desaturation in a large
      academic medical center in North America.

PMID- 28520719
TI  - Sex differences in management and outcomes of patients with atrial fibrillation
      in the Middle East: Gulf survey of atrial fibrillation events (Gulf SAFE).
AB  - Differences in the management of atrial fibrillation (AF) between men and women
      were investigated by using Gulf SAFE data in the Middle East. The study included
      2,043 patients presenting with AF to emergency room (ER) were prospectively
      enrolled and followed for one-year. Women were older, have higher body mass index
      (BMI), comorbidities, and health complications than men. With regard to
      management of AF, cardioversion was recommended more often for men (16.7% vs.
      9.3%), and underwent electrical cardioversion (2.2% vs. 1.1%). Women were
      prescribed digoxin more frequently than men (25.6% vs. 17.4%) and a significant
      number women received warfarin alone (31.1% vs. 8.7%). No difference between the
      sexes was noticed in One-year rates of stroke/transient ischemic attacks (TIA)
      and all-cause of mortality after one-year follow-up (3.1% men vs. 3.3% women, and
      7.5% vs. 7.4%). Older age (>= 65 years), smoking, alcohol use, CHADS2 scores >=5
      were some of the significant risk factors in men with AF. Suboptimal use of
      anticoagulants, higher mortality and stroke/TIA events at one year are high but
      similar between the sexes. ER management revealed high use of rate control
      strategy and high rate of hospital admission was noticed in women.

PMID- 28520721
TI  - On the slope of the regression between stem cell divisions and cancer risk, and
      the lack of correlation between stem cell divisions and environmental factors
      associated cancer risk.

PMID- 28520720
TI  - Identification of human short introns.
AB  - Canonical pre-mRNA splicing requires snRNPs and associated splicing factors to
      excise conserved intronic sequences, with a minimum intron length required for
      efficient splicing. Non-canonical splicing-intron excision without the
      spliceosome-has been documented; most notably, some tRNAs and the XBP1 mRNA
      contain short introns that are not removed by the spliceosome. There have been
      some efforts to identify additional short introns, but little is known about how
      many short introns are processed from mRNAs. Here, we report an approach to
      identify RNA short introns from RNA-Seq data, discriminating against small
      genomic deletions. We identify hundreds of short introns conserved among multiple
      human cell lines. These short introns are often alternatively spliced and are
      found in a variety of RNAs-both mRNAs and lncRNAs. Short intron splicing
      efficiency is increased by secondary structure, and we detect both canonical and
      non-canonical short introns. In many cases, splicing of these short introns from
      mRNAs is predicted to alter the reading frame and change protein output. Our
      findings imply that standard gene prediction models which often assume a lower
      limit for intron size fail to predict short introns effectively. We conclude that
      short introns are abundant in the human transcriptome, and short intron splicing
      represents an added layer to mRNA regulation.

PMID- 28520722
TI  - Altered detrusor contractility in MPTP-treated common marmosets with bladder
      hyperreflexia.
AB  - Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We
      now report on the contractility of the isolated primate detrusor strips devoid of
      nerve input and show that following MPTP, the amplitude and frequency of
      spontaneous contraction was increased. These responses were unaffected by
      dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively.
      Contractions by exogenous carbachol, histamine or ATP were similar and no
      differences in the magnitude of noradrenaline-induced relaxation were seen in
      detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix
      jacchus). However, the neurogenic contractions following electrical field
      stimulation of the intrinsic nerves (EFS) were markedly greater in strips
      obtained from MPTP treated animals. EFS evoked non-cholinergic contractions
      following atropine were also greater but the contribution of the cholinergic
      innervation as a proportion of the overall contraction was smaller in the
      detrusor strips of MPTP treated animals, suggesting a preferential enhancement of
      the non-cholinergic transmission. Although dopaminergic mechanism has been
      proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact
      bladder, the present data indicates that the increased neurogenically mediated
      contractions where no extrinsic innervation exists might be due to long-term
      adaptive changes locally as a result of the loss of the nigrostriatal output.

PMID- 28520723
TI  - Follicular size predicts success in artificial insemination with frozen-thawed
      sperm in donkeys.
AB  - In asses, semen collection, cryopreservation, and artificial insemination (AI)
      with frozen-thawed semen have been scarcely described and success rate,
      particularly following AI, is reportedly low. In the absence of reliable
      protocols, assisted reproductive technologies cannot support the conservation
      efforts aimed at endangered wild ass species and domestic donkey breeds. Two
      experiments were conducted in this study. In experiment 1 we evaluated freezing
      Abyssinian donkey (N = 5, 4 ejaculates each) spermatozoa using three freezing
      extenders (Berliner Cryomedium + glycerol, BC+G; BotuCrio, BOTU; INRAFreeze,
      INRA) and two cryopreservation techniques (liquid nitrogen vapour, LNV;
      directional freezing, DF). Post-thaw evaluation indicated that BOTU and INRA were
      similar and both superior to BC+G (P <= 0.004 for all motility tests), and that
      DF was superior to LNV (P < 0.002 for all evaluation parameters). In experiment
      2, relying on these results, we used Abyssinian donkey sperm frozen in BOTU and
      INRA by DF for AI (N = 20). Prior to AI, thawed samples were diluted in
      corresponding centrifugation media or autologous seminal fluids at 1:1 ratio. No
      difference was found between BOTU and INRA or between the addition of seminal
      fluids or media, all resulting in ~50% pregnancy, and no differences were noted
      between males (N = 4). The size of pre-ovulatory follicle was a significant (P =
      0.001) predictor for AI success with 9/10 pregnancies occurring when follicular
      size ranged between 33.1-37.4 mm, no pregnancy when it was smaller, and only one
      when larger. A number of ass species face the risk of extinction. Knowledge
      gained in this study on the Abyssinian donkey can be customised and transferred
      to its closely related endangered species and breeds.

PMID- 28520724
TI  - Development of a movement-based in vitro screening assay for the identification
      of new anti-cestodal compounds.
AB  - Intestinal cestodes are infecting millions of people and livestock worldwide, but
      treatment is mainly based on one drug: praziquantel. The identification of new
      anti-cestodal compounds is hampered by the lack of suitable screening assays. It
      is difficult, or even impossible, to evaluate drugs against adult cestodes in
      vitro due to the fact that these parasites cannot be cultured in microwell
      plates, and adult and larval stages in most cases represent different organisms
      in terms of size, morphology, and metabolic requirements. We here present an in
      vitro-drug screening assay based on Echinococcus multilocularis protoscoleces,
      which represent precursors of the scolex (hence the anterior part) of the adult
      tapeworm. This movement-based assay can serve as a model for an adult cestode
      screen. Protoscoleces are produced in large numbers in Mongolian gerbils and
      mice, their movement is measured and quantified by image analysis, and active
      compounds are directly assessed in terms of morphological effects. The use of the
      384-well format minimizes the amount of parasites and compounds needed and allows
      rapid screening of a large number of chemicals. Standard drugs showed the
      expected dose-dependent effect on movement and morphology of the protoscoleces.
      Interestingly, praziquantel inhibited movement only partially within 12 h of
      treatment (at concentrations as high as 100 ppm) and did thus not act
      parasiticidal, which was also confirmed by trypan blue staining. Enantiomers of
      praziquantel showed a clear difference in their minimal inhibitory concentration
      in the motility assay and (R)-(-)-praziquantel was 185 times more active than (S)
      (-)-praziquantel. One compound named MMV665807, which was obtained from the open
      access MMV (Medicines for Malaria Venture) Malaria box, strongly impaired
      motility and viability of protoscoleces. Corresponding morphological alterations
      were visualized by scanning electron microscopy, and demonstrated that this
      compound exhibits a mode of action clearly distinct from praziquantel. Thus,
      MMV665807 represents an interesting lead for further evaluation.

PMID- 28520726
TI  - Losing a jewel-Rapid declines in Myanmar's intact forests from 2002-2014.
AB  - New and rapid political and economic changes in Myanmar are increasing the
      pressures on the country's forests. Yet, little is known about the past and
      current condition of these forests and how fast they are declining. We mapped
      forest cover in Myanmar through a consortium of international organizations and
      environmental non-governmental groups, using freely-available public domain data
      and open source software tools. We used Landsat satellite imagery to assess the
      condition and spatial distribution of Myanmar's intact and degraded forests with
      special focus on changes in intact forest between 2002 and 2014. We found that
      forests cover 42,365,729 ha or 63% of Myanmar, making it one of the most forested
      countries in the region. However, severe logging, expanding plantations, and
      degradation pose increasing threats. Only 38% of the country's forests can be
      considered intact with canopy cover >80%. Between 2002 and 2014, intact forests
      declined at a rate of 0.94% annually, totaling more than 2 million ha forest
      loss. Losses can be extremely high locally and we identified 9 townships as
      forest conversion hotspots. We also delineated 13 large (>100,000 ha) and
      contiguous intact forest landscapes, which are dispersed across Myanmar. The
      Northern Forest Complex supports four of these landscapes, totaling over 6.1
      million ha of intact forest, followed by the Southern Forest Complex with three
      landscapes, comprising 1.5 million ha. These remaining contiguous forest
      landscape should have high priority for protection. Our project demonstrates how
      open source data and software can be used to develop and share critical
      information on forests when such data are not readily available elsewhere. We
      provide all data, code, and outputs freely via the internet at (for scripts:
      https://bitbucket.org/rsbiodiv/; for the data:
      http://geonode.themimu.info/layers/geonode%3Amyan_lvl2_smoothed_dec2015_resamp).

PMID- 28520725
TI  - Reading positional codes with fMRI: Problems and solutions.
AB  - Neural mechanisms which bind items into sequences have been investigated in a
      large body of research in animal neurophysiology and human neuroimaging. However,
      a major problem in interpreting this data arises from a fact that several
      unrelated processes, such as memory load, sensory adaptation, and reward
      expectation, also change in a consistent manner as the sequence unfolds. In this
      paper we use computational simulations and data from two fMRI experiments to show
      that a host of unrelated neural processes can masquerade as sequence
      representations. We show that dissociating such unrelated processes from a
      dedicated sequence representation is an especially difficult problem for fMRI
      data, which is almost exclusively the modality used in human experiments. We
      suggest that such fMRI results must be treated with caution and in many cases the
      assumed neural representation might actually reflect unrelated processes.

PMID- 28520727
TI  - Predictors of decision ambivalence and the differences between actual living
      liver donors and potential living liver donors.
AB  - BACKGROUND: The decision to become a living liver donor is a stressful event.
      Ambivalence in decision making may result in psychological distress. Thus, the
      purpose of this study was to provide a description of the ambivalence of
      potential living liver donors, to examine the predictors of ambivalence, and to
      compare the ambivalence of potential living liver donors with that of actual
      living liver donors. METHODS: This descriptive and correlational study was
      conducted in a medical center from August 2013 to December 2015. Self-reported
      questionnaires were used to collect data. A total of 263 potential living liver
      donors who were assessed for donation to their parents were included in this
      study. RESULTS: The mean age of the total sample was 30.7 years (SD = 6.39, range
      = 20-47), and males comprised 53.6% of the sample. The majority of the potential
      donors had a college education (70.8%) and were single (63.5%). Of the total
      sample, the mean score for ambivalence was 4.27 (SD = 1.87, range = 0-7).
      Multivariate analysis revealed that the Mental Component Summary (MCS) of quality
      of life (beta = -0.24, p < 0.01), family support (beta = -0.17, p = 0.007), and
      intimacy (beta = -0.13, p = 0.04) were significant protective predictors of
      ambivalence. Actual living liver donors had significantly lower ambivalence (3.82
      versus 4.60), higher intimacy with recipients (3.55 versus 3.34), higher MCS
      (45.26 versus 42.80), and higher family support (34.39 versus 29.79) than did the
      remaining potential living liver donors. CONCLUSION: Ambivalence is common in
      potential living liver donors. The MCS of quality of life, family support, and
      intimacy were protective predictors in terms of ambivalence. Future research
      should explore other factors and design interventions targeted toward reducing
      ambivalence, promoting family support, and enhancing the mental dimensions of
      quality of life in potential living liver donors.

PMID- 28520728
TI  - Cost-effectiveness of hepatitis C treatment using generic direct-acting
      antivirals available in India.
AB  - BACKGROUND & AIMS: Availability of directly-acting antivirals (DAAs) has changed
      the treatment landscape of hepatitis C virus (HCV) infection. The high price of
      DAAs has restricted their use in several countries. However, in some countries
      such as India, generic DAAs are available at much cheaper price. This study
      examined whether generic DAAs could be cost-saving and how long it would take for
      the treatment to become cost-saving/effective. METHODS: A previously-validated,
      mathematical model was adapted to the HCV-infected population in India to compare
      the outcomes of no treatment versus treatment with DAAs. Model parameters were
      estimated from published studies. Cost-effectiveness of HCV treatment using
      available DAAs was calculated, using a payer's perspective. We estimated quality
      adjusted life years (QALYs), disability-adjusted life years (DALYs), total costs,
      and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and
      probabilistic sensitivity analyses were conducted. RESULTS: Compared with no
      treatment, the use of generic DAAs in Indian HCV patients would increase the life
      expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce
      the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost
      effective within 2 years, and cost-saving within 10 years of its initiation
      overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV
      infected persons could prevent 3400-3850 decompensated cirrhosis, 1800-2500 HCC,
      and 4000-4550 liver-related deaths. The results were sensitive to the costs of
      DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and
      quality of life after sustained virologic response. CONCLUSIONS: Treatment with
      generic DAAs available in India will improve patient outcomes, provide a good
      value for money within 2 years, and be ultimately cost-saving. Therefore, in this
      and similar settings, HCV treatment should be a priority from a public health as
      well an economic perspective.

PMID- 28520729
TI  - Top quality blastocyst formation rates in relation to progesterone levels on the
      day of oocyte maturation in GnRH antagonist IVF/ICSI cycles.
AB  - Cycles with progesterone elevation during controlled ovarian stimulation (COS)
      for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well
      recognized detrimental effect of high progesterone levels on endometrial
      receptivity. However, also a detrimental effect of elevated progesterone on day-3
      embryo quality has recently been found with regards to top quality embryo
      formation rate. Because blastocyst culture and cryopreservation are largely
      adopted, we deemed relevant to determine whether this detrimental effect is also
      seen on blastocyst quality on day 5-6. This issue was investigated through a
      large two-center retrospective study including 986 GnRH antagonist IVF/ICSI
      cycles and using top quality blastocyst formation rate as the main outcome.
      Results showed that on multivariate analysis sperm motility (p<0.01) and
      progesterone levels at ovulation triggering (p = 0.01) were the only two
      variables that significantly predicted top quality blastocyst formation rate
      after adjusting for relevant factors including female age, BMI, basal AMH and
      total dose of FSH used for COS. More specifically, progesterone levels at
      induction showed an inverse relation with top quality blastocyst formation
      (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis
      identified P level >1.49 ng/ml as the best cut-off for identification of patients
      at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study
      is the first to investigate the top quality blastocyst formation rate in relation
      to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone
      is associated with lower rates of top quality blastocyst. Hence, the advantages
      of prolonging COS to maximize the number of collected oocytes might eventually be
      hindered by a decrease in top quality blastocysts available for transfer, if
      increasing progesterone levels are observed. This observation extends the results
      of two recent studies focused on day-3 embryos and deserves further research.

PMID- 28520731
TI  - Genetically engineered probiotic for the treatment of phenylketonuria (PKU);
      assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.
AB  - Phenylketonuria (PKU) is a genetic disease characterized by the inability to
      convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the
      importance of gut microbes in digestion, a genetically engineered microbe could
      potentially degrade some ingested phenylalanine from the diet prior to
      absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis
      (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in
      Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was
      determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU
      model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined
      conditions for freeze-drying and delivery of bacteria. Animals showed reduced
      blood phe within three to four days of treatment with pHENOMMenal probiotic, and
      blood phe concentrations remained significantly reduced (P < 0.0005) compared to
      untreated controls during the course of experiments. Although pHENOMMenal
      probiotic could be cultured from fecal samples at four months post treatment, it
      could no longer be cultivated from feces at eight months post treatment,
      indicating eventual loss of the microbe from the gut. Preliminary screens during
      experimentation found no immune response to AvPAL. Collectively these studies
      provide data for the use of a genetically engineered probiotic as a potential
      treatment for PKU.

PMID- 28520730
TI  - Analysis of heterogeneity in T2-weighted MR images can differentiate
      pseudoprogression from progression in glioblastoma.
AB  - PURPOSE: To develop an image analysis technique that distinguishes
      pseudoprogression from true progression by analyzing tumour heterogeneity in T2
      weighted images using topological descriptors of image heterogeneity called
      Minkowski functionals (MFs). METHODS: Using a retrospective patient cohort (n =
      50), and blinded to treatment response outcome, unsupervised feature estimation
      was performed to investigate MFs for the presence of outliers, potential
      confounders, and sensitivity to treatment response. The progression and
      pseudoprogression groups were then unblinded and supervised feature selection was
      performed using MFs, size and signal intensity features. A support vector machine
      model was obtained and evaluated using a prospective test cohort. RESULTS: The
      model gave a classification accuracy, using a combination of MFs and size
      features, of more than 85% in both retrospective and prospective datasets. A
      different feature selection method (Random Forest) and classifier (Lasso) gave
      the same results. Although not apparent to the reporting radiologist, the T2
      weighted hyperintensity phenotype of those patients with progression was
      heterogeneous, large and frond-like when compared to those with
      pseudoprogression. CONCLUSION: Analysis of heterogeneity, in T2-weighted MR
      images, which are acquired routinely in the clinic, has the potential to detect
      an earlier treatment response allowing an early change in treatment strategy.
      Prospective validation of this technique in larger datasets is required.

PMID- 28520732
TI  - Differential gene expression along the animal-vegetal axis in the ascidian embryo
      is maintained by a dual functional protein Foxd.
AB  - In many animal embryos, a specific gene expression pattern is established along
      the animal-vegetal axis soon after zygotic transcription begins. In the embryo of
      the ascidian Ciona intestinalis, soon after the division that separates animal
      and vegetal hemispheres into distinct blastomeres, maternal Gata.a and beta
      catenin activate specific genes in the animal and vegetal blastomeres,
      respectively. On the basis of these initial distinct gene expression patterns,
      gene regulatory networks promote animal cells to become ectodermal tissues and
      vegetal cells to become endomesodermal tissues and a part of the nerve cord. In
      the vegetal hemisphere, beta-catenin directly activates Foxd, an essential
      transcription factor gene for specifying endomesodermal fates. In the present
      study, we found that Foxd also represses the expression of genes that are
      activated specifically in the animal hemisphere, including Dmrt1, Prdm1-r.a
      (Bz1), Prdm1-r.b (Bz2), and Otx. A reporter assay showed that Dmrt1 expression
      was directly repressed by Foxd, and a chromatin immunoprecipitation assay showed
      that Foxd was bound to the upstream regions of Dmrt1, Prdm1-r.a, Prdm1-r.b, and
      Otx. Thus, Foxd has a dual function of activating specific gene expression in the
      vegetal hemisphere and of repressing the expression of genes that are normally
      expressed in the animal hemisphere. This dual function stabilizes the initial
      patterning along the animal-vegetal axis by beta-catenin and Gata.a.

PMID- 28520733
TI  - Environmental DNA method for estimating salamander distribution in headwater
      streams, and a comparison of water sampling methods.
AB  - Environmental DNA (eDNA) has recently been used for detecting the distribution of
      macroorganisms in various aquatic habitats. In this study, we applied an eDNA
      method to estimate the distribution of the Japanese clawed salamander,
      Onychodactylus japonicus, in headwater streams. Additionally, we compared the
      detection of eDNA and hand-capturing methods used for determining the
      distribution of O. japonicus. For eDNA detection, we designed a qPCR primer/probe
      set for O. japonicus using the 12S rRNA region. We detected the eDNA of O.
      japonicus at all sites (with the exception of one), where we also observed them
      by hand-capturing. Additionally, we detected eDNA at two sites where we were
      unable to observe individuals using the hand-capturing method. Moreover, we found
      that eDNA concentrations and detection rates of the two water sampling areas
      (stream surface and under stones) were not significantly different, although the
      eDNA concentration in the water under stones was more varied than that on the
      surface. We, therefore, conclude that eDNA methods could be used to determine the
      distribution of macroorganisms inhabiting headwater systems by using samples
      collected from the surface of the water.

PMID- 28520734
TI  - Interfacial mechanisms for stability of surfactant-laden films.
AB  - Thin liquid films are central to everyday life. They are ubiquitous in modern
      technology (pharmaceuticals, coatings), consumer products (foams, emulsions) and
      also serve vital biological functions (tear film of the eye, pulmonary
      surfactants in the lung). A common feature in all these examples is the presence
      of surface-active molecules at the air-liquid interface. Though they form only
      molecular-thin layers, these surfactants produce complex surface stresses on the
      free surface, which have important consequences for the dynamics and stability of
      the underlying thin liquid film. Here we conduct simple thinning experiments to
      explore the fundamental mechanisms that allow the surfactant molecules to slow
      the gravity-driven drainage of the underlying film. We present a simple model
      that works for both soluble and insoluble surfactant systems in the limit of
      negligible adsorption-desorption dynamics. We show that surfactants with finite
      surface rheology influence bulk flow through viscoelastic interfacial stresses,
      while surfactants with inviscid surfaces achieve stability through opposing
      surface-tension induced Marangoni flows.

PMID- 28520735
TI  - Pain in methadone patients: Time to address undertreatment and suicide risk (ANRS
      Methaville trial).
AB  - BACKGROUND: Pain in opioid-dependent patients is common but data measuring the
      course of pain (and its correlates) using validated scales in patients initiating
      methadone treatment are sparse. We aimed to assess pain and its interference in
      daily life, associated correlates, and undertreatment before and during methadone
      treatment. METHODS: This is a secondary analysis using longitudinal data of a
      randomized trial comparing two methadone initiation models. We assessed the
      effect of methadone initiation and other correlates on pain intensity and
      interference (using the Brief Pain Inventory) at months 0, 6 and 12 using a mixed
      multinomial logistic regression model. RESULTS: The study group comprised 168
      patients who had data for either pain intensity or interference for at least one
      visit. Moderate to severe pain was reported in 12.9% of patients at M0, 5.4% at
      M6 and 7.3% at M12. Substantial interference with daily functioning was reported
      in 36.0% at M0, 14.5% at M6 and 17.1% at M12. Of the 98 visits where patients
      reported moderate to severe pain or substantial interference, 55.1% reported no
      treatment for pain relief, non-opioid analgesics were reported by 34.7%, opioid
      analgesics by 3.1% and both opioid and non-opioid analgesics by 7.1%. Methadone
      was associated with decreased pain intensity at 6 months (OR = 0.29, p = 0.04)
      and 12 months (OR = 0.30, p = 0.05) of follow-up and tended to be associated with
      substantial pain interference. Suicide risk was associated with both pain
      intensity and pain interference. CONCLUSIONS: Methadone in opioid-dependent
      patients can reduce pain. However, undertreatment of pain in methadone patients
      remains a major clinical concern. Patients with pain are at higher risk of
      suicide. Adequate screening and management of pain in this population is a
      priority and needs to be integrated into routine comprehensive care.

PMID- 28520736
TI  - The bantam microRNA acts through Numb to exert cell growth control and feedback
      regulation of Notch in tumor-forming stem cells in the Drosophila brain.
AB  - Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs)
      and other tissue stem cells. Its deregulation compromises tissue homeostasis and
      contributes to tumorigenesis and other diseases. How N regulates stem cell
      behavior in health and disease is not well understood. Here we show that N
      regulates bantam (ban) microRNA to impact cell growth, a process key to NSC
      maintenance and particularly relied upon by tumor-forming cancer stem cells.
      Notch signaling directly regulates ban expression at the transcriptional level,
      and ban in turn feedback regulates N activity through negative regulation of the
      Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the
      robustness of N signaling activity and NSC fate. Moreover, we show that a Numb
      Myc axis mediates the effects of ban on nucleolar and cellular growth
      independently or downstream of N. Our results highlight intricate transcriptional
      as well as translational control mechanisms and feedback regulation in the N
      signaling network, with important implications for NSC biology and cancer
      biology.

PMID- 28520737
TI  - Outdoor spatial spraying against dengue: A false sense of security among
      inhabitants of Hermosillo, Mexico.
AB  - BACKGROUND: Government-administered adulticiding is frequently conducted in
      response to dengue transmission worldwide. Anecdotal evidence suggests that
      spraying may create a "false sense of security" for residents. Our objective was
      to determine if there was an association between residents' reporting outdoor
      spatial insecticide spraying as way to prevent dengue transmission and both their
      reported frequency of dengue prevention practices and household entomological
      indices in Hermosillo, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: A non
      probabilistic survey of 400 households was conducted in August 2014. An oral
      questionnaire was administered to an adult resident and the outer premises of the
      home were inspected for water-holding containers and presence of Ae. aegypti
      larvae and pupae. Self-reported frequency of prevention practices were assessed
      among residents who reported outdoor spatial spraying as a strategy to prevent
      dengue (n = 93) and those who did not (n = 307). Mixed effects negative binomial
      regression was used to assess associations between resident's reporting spraying
      as a means to prevent dengue and container indices. Mixed effects logistic
      regression was used to determine associations with presence/absence of larvae and
      pupae. Those reporting spatial spraying disposed of trash less frequently and
      spent less time indoors to avoid mosquitoes. They also used insecticides and
      larvicides more often and covered their water containers more frequently. Their
      backyards had more containers positive for Ae. aegypti (RR = 1.92) and there was
      a higher probability of finding one or more Ae. aegypti pupae (OR = 2.20). Survey
      respondents that reported spatial spraying prevented dengue were more likely to
      be older and were exposed to fewer media sources regarding prevention.
      CONCLUSIONS/SIGNIFICANCE: The results suggest that the perception that outdoor
      spatial spraying prevents dengue is associated with lower adoption of prevention
      practices and higher entomological risk. This provides some support to the
      hypothesis that spraying may lead to a "false sense of security". Further
      investigations to clarify this relationship should be conducted. Government
      campaigns should emphasize the difficulty in controlling Ae. aegypti mosquitoes
      and the need for both government and community action to minimize risk of dengue
      transmission.

PMID- 28520738
TI  - Pediatric fluoroquinolone prescription in South Korea before and after a
      regulatory intervention: A nationwide study, 2007-2015.
AB  - OBJECTIVE: To investigate the impact of national implementation of age
      restriction on fluoroquinolone prescription in children and adolescents. METHODS:
      Data collected from the database of Health Insurance Review and Assessment
      Service in South Korea, a national health insurance system to analyze
      fluoroquinolone prescribing practice in children and adolescents younger than 18
      years, between 2007 and 2015. The age restriction was implemented in December
      2009. The annual prescription rate of FQ per 100,000 person-years was calculated
      and an autoregressive model was used to predict the prescription pattern if an
      intervention had not occurred. RESULTS: A total of 505,859 children received
      systemic fluoroquinolone during the study period-297,054 ciprofloxacin, and
      208,805 levofloxacin. After implementation of the drug utilization review
      program, the annual prescription rate for ciprofloxacin declined by 97.5% (from
      840 to 21 per 100,000 person-years, P < 0.001), and for levofloxacin by 96.4%
      (from 598 to 11 per 100,000 person-years, P < 0.001). The decline was more
      dramatic in the outpatient setting than in the inpatient setting for both drugs.
      CONCLUSION: The dramatic and sustained decline in prescription number and change
      in prescription pattern after the regulatory action suggests that the
      implementation under drug utilization review program was successful in
      controlling excessive and inappropriate use of fluoroquinolones in children,
      possibly guiding towards more judicious and selective prescription behavior.

PMID- 28520740
TI  - Ascertaining the impact of catastrophic events on dengue outbreak: The 2014 gas
      explosions in Kaohsiung, Taiwan.
AB  - Infectious disease outbreaks often occur in the aftermath of catastrophic events,
      either natural or man-made. While natural disasters such as typhoons/hurricanes,
      flooding and earthquakes have been known to increase the risk of infectious
      disease outbreak, the impact of anthropogenic disasters is less well-understood.
      Kaohsiung City is located in southern Taiwan, where most dengue outbreaks had
      occurred in the past two decades. It is also the center of petrochemical industry
      in Taiwan with pipelines running underneath city streets. Multiple underground
      gas explosions occurred in Kaohsiung in the evening of July 31, 2014 due to
      chemical leaks in the pipelines. The explosions caused 32 deaths, including five
      firefighters and two volunteer firefighters, and injured 321 persons.
      Historically, dengue outbreaks in southern Taiwan occurred mostly in small
      numbers of around 2000 cases or less, except in 2002 with over 5000 cases.
      However, in the months after the gas explosions, the city reported 14528 lab
      confirmed dengue cases from August to December. To investigate the possible
      impact, if any, of the gas explosions on this record-breaking dengue outbreak, a
      simple mathematical model, the Richards model, is utilized to study the temporal
      patterns of the spread of dengue in the districts of Kaohsiung in the proximity
      of the explosion sites and to pinpoint the waves of infections that had occurred
      in each district in the aftermath of the gas explosions. The reproduction number
      of each wave in each district is also computed. In the aftermath of the gas
      explosions, early waves occurred 4-5 days (which coincides with the minimum of
      human intrinsic incubation period for dengue) later in districts with multiple
      waves. The gas explosions likely impacted the timing of the waves, but their
      impact on the magnitude of the 2014 outbreak remains unclear. The modeling
      suggests the need for public health surveillance and preparedness in the
      aftermath of future disasters.

PMID- 28520739
TI  - Timing-dependent LTP and LTD in mouse primary visual cortex following different
      visual deprivation models.
AB  - Visual deprivation during the critical period induces long-lasting changes in
      cortical circuitry by adaptively modifying neuro-transmission and synaptic
      connectivity at synapses. Spike timing-dependent plasticity (STDP) is considered
      a strong candidate for experience-dependent changes. However, the visual
      deprivation forms that affect timing-dependent long-term potentiation(LTP) and
      long-term depression(LTD) remain unclear. Here, we demonstrated the temporal
      window changes of tLTP and tLTD, elicited by coincidental pre- and post-synaptic
      firing, following different modes of 6-day visual deprivation. Markedly broader
      temporal windows were found in robust tLTP and tLTD in the V1M of the deprived
      visual cortex in mice after 6-day MD and DE. The underlying mechanism for the
      changes seen with visual deprivation in juvenile mice using 6 days of dark
      exposure or monocular lid suture involves an increased fraction of NR2b
      containing NMDAR and the consequent prolongation of NMDAR-mediated response
      duration. Moreover, a decrease in NR2A protein expression at the synapse is
      attributable to the reduction of the NR2A/2B ratio in the deprived cortex.

PMID- 28520741
TI  - Highly regulated growth and development of the Ediacara macrofossil Dickinsonia
      costata.
AB  - The Ediacara Biota represents the oldest fossil evidence for the appearance of
      animals but linking these taxa to specific clades has proved challenging.
      Dickinsonia is an abundant, apparently bilaterally symmetrical Ediacara fossil
      with uncertain affinities. We identified and measured key morphological features
      of over 900 specimens of Dickinsonia costata from the Ediacara Member, South
      Australia to characterize patterns in growth and morphology. Here we show that
      development in Dickinsonia costata was surprisingly highly regulated to maintain
      an ovoid shape via terminal addition and the predictable expansion of modules.
      This result, along with other characters found in Dickinsonia suggests that it
      does not belong within known animal groups, but that it utilized some of the
      developmental gene networks of bilaterians, a result predicted by gene sequencing
      of basal metazoans but previously unidentified in the fossil record. Dickinsonia
      thus represents an extinct clade located between sponges and the last common
      ancestor of Protostomes and Deuterostomes, and likely belongs within the
      Eumetazoa.

PMID- 28520742
TI  - Experimental outgassing of toxic chemicals to simulate the characteristics of
      hazards tainting globally shipped products.
AB  - Ambient monitoring analyses may identify potential new public health hazards such
      as residual levels of fumigants and industrial chemicals off gassing from
      products and goods shipped globally. We analyzed container air with gas
      chromatography coupled to mass spectrometry (TD-2D-GC-MS/FPD) and assessed
      whether the concentration of the volatiles benzene and 1,2-dichloroethane
      exceeded recommended exposure limits (REL). Products were taken from transport
      containers and analyzed for outgassing of volatiles. Furthermore, experimental
      outgassing was performed on packaging materials and textiles, to simulate the
      hazards tainting from globally shipped goods. The mean amounts of benzene in
      analyzed container air were 698-fold higher, and those of ethylene dichloride
      were 4.5-fold higher than the corresponding REL. More than 90% of all containers
      struck with toluene residues higher than its REL. For 1,2-dichloroethane 53% of
      containers, transporting shoes exceeded the REL. In standardized experimental
      fumigation of various products, outgassing of 1,2-dichloroethane under controlled
      laboratory conditions took up to several months. Globally produced transported
      products tainted with toxic industrial chemicals may contribute to the mixture of
      volatiles in indoor air as they are likely to emit for a long period. These
      results need to be taken into account for further evaluation of safety standards
      applying to workers and consumers.

PMID- 28520744
TI  - Indoor simulations reveal differences among plant species in capturing
      particulate matter.
AB  - A number of studies have focused on the capacity of urban trees and shrubs to
      serve as efficient biological filters to mitigate air pollution. In this study,
      five different tree species were assessed for this function. Kerria japonica,
      Sophora japonica, Philadelphus pekinensis, Gleditsia sinensis, and Prunus persica
      'Atropurpurea' were tested in a deposition chamber using (NH4)2SO4 particles. We
      quantified and compared the capability of all tested trees to remove particles by
      assessing deposition velocity, a measure of the ability to remove particles. When
      placed in the deposition chamber, S. japonica had the greatest deposition
      velocity, followed by Philadelphus pekinensis, G. sinensis, Prunus persica
      'Atropurpurea,' and K. japonica, in descending order. In addition, the comparison
      of deposition velocities among these species suggested that certain leaf
      geometries and surface characteristics of broadleaf trees, such as trichomes and
      grooves, increased particle capture. However, these results change under a
      different simulation condition using ambient air, suggesting that some trees
      actually increase pollutant number concentrations more than reduce particle
      concentration. This outcome can be explained by the aerodynamic effect of trees
      exceeding the filtering capacity of vegetation under some conditions. This
      highlights the difficulty of generalizing species selection criteria for practice
      use. Accordingly, our results indicate that using vegetation to reduce particle
      pollution and improve the air quality is not a universally advisable and viable
      solution.

PMID- 28520743
TI  - Whole brain volume changes and its correlation with clinical symptom severity in
      patients with schizophrenia: A DARTEL-based VBM study.
AB  - The purpose of this study was to evaluate gray matter (GM) and white matter (WM)
      volume alterations in whole-brain structures in patients with schizophrenia and
      healthy controls using voxel-based morphometry (VBM), and further to assess the
      correlation between GM and WM volume variations and symptom severity in
      schizophrenia. A total of 22 patients with schizophrenia and 22 age-matched
      healthy controls participated. Magnetic resonance image data were processed using
      SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie
      algebra (DARTEL) algorithm. Patients with schizophrenia exhibited significantly
      decreased GM volumes of the insula, superior temporal gyrus (STG), gyrus rectus,
      and anterior cingulate cortex (ACC) compared with healthy controls. The GM
      volumes of the STG and gyrus rectus were negatively correlated with the positive
      scales on the Positive and Negative Syndrome Scale (PANSS) and those of the STG
      and ACC were negatively correlated with the negative scales. The durations of
      illness in schizophrenia were negatively correlated with the GM volumes of the
      insula, STG, and ACC. Patients with schizophrenia exhibited significantly
      decreased WM volumes of the superior frontal gyrus, inferior temporal gyrus, and
      STG. The WM volumes of the STG were negatively correlated with the duration of
      illness. Our findings suggest that GM and WM volume abnormalities in the STG are
      associated with the psychopathology of schizophrenia.

PMID- 28520745
TI  - High handaxe symmetry at the beginning of the European Acheulian: The data from
      la Noira (France) in context.
AB  - In the last few decades, new discoveries have pushed the beginning of the biface
      rich European Acheulian from 500 thousand years (ka) ago back to at least 700 ka,
      and possibly to 1 million years (Ma) ago. It remains, however, unclear to date if
      handaxes arrived in Europe as a fully developed technology or if they evolved
      locally from core-and-flake industries. This issue is also linked with another
      long-standing debate on the existence and behavioral, cognitive, and social
      meaning of a possibly chronological trend for increased handaxe symmetry
      throughout the Lower Paleolithic. The newly discovered sites can provide a link
      between the much older Acheulian in Africa and the Levant and the well-known
      assemblages from the later European Acheulian, enabling a rigorous testing of
      these hypotheses using modern morphometric methods. Here we use the Continuous
      Symmetry Measure (CSM) method to quantify handaxe symmetry at la Noira, a newly
      excavated site in central France, which features two archaeological levels,
      respectively ca. 700 ka and 500 ka old. In order to provide a context for the new
      data, we use a large aggregate from the well-known 500 ka old site of Boxgrove,
      England. We show that handaxes from the oldest layer at la Noira, although on
      average less symmetric than both those from the younger layers at the same site
      and than those from Boxgrove, are nevertheless much more symmetric than other
      early Acheulian specimens evaluated using the CSM method. We also correlate
      trends in symmetry to degree of reduction, demonstrating that raw material
      availability and discard patterns may affect observed symmetry values. We
      conclude that it is likely that, by the time the Acheulian arrived in Europe, its
      makers were, from a cognitive and motor-control point of view, already capable of
      producing the symmetric variant of this technology.

PMID- 28520747
TI  - An index-based algorithm for fast on-line query processing of latent semantic
      analysis.
AB  - Latent Semantic Analysis (LSA) is widely used for finding the documents whose
      semantic is similar to the query of keywords. Although LSA yield promising
      similar results, the existing LSA algorithms involve lots of unnecessary
      operations in similarity computation and candidate check during on-line query
      processing, which is expensive in terms of time cost and cannot efficiently
      response the query request especially when the dataset becomes large. In this
      paper, we study the efficiency problem of on-line query processing for LSA
      towards efficiently searching the similar documents to a given query. We rewrite
      the similarity equation of LSA combined with an intermediate value called partial
      similarity that is stored in a designed index called partial index. For reducing
      the searching space, we give an approximate form of similarity equation, and then
      develop an efficient algorithm for building partial index, which skips the
      partial similarities lower than a given threshold theta. Based on partial index,
      we develop an efficient algorithm called ILSA for supporting fast on-line query
      processing. The given query is transformed into a pseudo document vector, and the
      similarities between query and candidate documents are computed by accumulating
      the partial similarities obtained from the index nodes corresponds to non-zero
      entries in the pseudo document vector. Compared to the LSA algorithm, ILSA
      reduces the time cost of on-line query processing by pruning the candidate
      documents that are not promising and skipping the operations that make little
      contribution to similarity scores. Extensive experiments through comparison with
      LSA have been done, which demonstrate the efficiency and effectiveness of our
      proposed algorithm.

PMID- 28520746
TI  - DNA recognition by an RNA-guided bacterial Argonaute.
AB  - Argonaute (Ago) proteins are widespread in prokaryotes and eukaryotes and share a
      four-domain architecture capable of RNA- or DNA-guided nucleic acid recognition.
      Previous studies identified a prokaryotic Argonaute protein from the eubacterium
      Marinitoga piezophila (MpAgo), which binds preferentially to 5'-hydroxylated
      guide RNAs and cleaves single-stranded RNA (ssRNA) and DNA (ssDNA) targets. Here
      we present a 3.2 A resolution crystal structure of MpAgo bound to a 21-nucleotide
      RNA guide and a complementary 21-nucleotide ssDNA substrate. Comparison of this
      ternary complex to other target-bound Argonaute structures reveals a unique
      orientation of the N-terminal domain, resulting in a straight helical axis of the
      entire RNA-DNA heteroduplex through the central cleft of the protein.
      Additionally, mismatches introduced into the heteroduplex reduce MpAgo cleavage
      efficiency with a symmetric profile centered around the middle of the helix. This
      pattern differs from the canonical mismatch tolerance of other Argonautes, which
      display decreased cleavage efficiency for substrates bearing sequence mismatches
      to the 5' region of the guide strand. This structural analysis of MpAgo bound to
      a hybrid helix advances our understanding of the diversity of target recognition
      mechanisms by Argonaute proteins.

PMID- 28520748
TI  - Inflammation-related microRNA expression level in the bovine milk is affected by
      mastitis.
AB  - MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated
      with many diseases including inflammation. We aimed to identify inflammation
      related miRNA expression level in the bovine mastitis milk. Expression level of
      inflammation-related miRNA in milk from mastitis-affected and normal cows was
      analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155,
      miR-222, and miR-383 was significantly upregulated in California mastitis test
      positive (CMT+) milk. We further analyzed these miRNA using a chip-based
      QuantStudio Digital PCR System. The digital PCR results correlated with those of
      qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR
      383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+
      milk. These miRNA exhibited sensitivity and specificity greater than 80% for
      differentiating between CMT+ milk and normal milk. Our findings suggest that
      inflammation-related miRNA expression level in the bovine milk was affected by
      mastitis, and miRNA in milk have potential for use as biomarkers of bovine
      mastitis.

PMID- 28520749
TI  - Access and response to direct antiviral agents (DAA) in HIV-HCV co-infected
      patients in Italy: Data from the Icona cohort.
AB  - BACKGROUND: Real-life data on access and response to direct antiviral agents
      (DAA) in HIV-HCV coinfected individuals are lacking. METHODS: HCV viremic, HIV
      positive patients from Icona and Hepaicona cohorts naive to DAA by January 2013
      were included. Access and predictors of starting DAA were evaluated. Switches of
      antiretroviral drugs at starting DAA were described. We calculated sustained
      virological response (SVR12) in those reaching 12 weeks after end-of-treatment
      (EOT), and defined treatment failure (TF) as discontinuation of DAA before EOT or
      non-SVR12. Statistical analyses included Kaplan-Meier curves, univariable and
      multivariable analyses evaluating predictors of access to DAA and of treatment
      outcome (non-SVR and TF). RESULTS: 2,607 patients included. During a median
      follow-up of 38 (IQR:30-41) months, 920 (35.3%) patients started DAA. Eligibility
      for reimbursement was the strongest predictor to access to treatment: 761/1,090
      (69.8%) eligible and 159/1,517 (10.5%) non-eligible to DAA reimbursement. Older
      age, HIV-RNA<=50 copies/mL were associated to faster DAA initiation, higher CD4
      count and HCV-genotype 3 with delayed DAA initiation in those eligible to DAA
      reimbursement. Up to 28% of patients (36% of those on ritonavir-boosted protease
      inhibitors, PI/r) underwent antiretroviral (ART) modification at DAA initiation.
      545/595 (91.6%) patients reaching EOT achieved SVR12. Overall, TF occurred in
      61/606 patients (10.1%), with 11 discontinuing DAA before EOT. Suboptimal DAA was
      the only independent predictor of both non-SVR12 (AHR 2.52, 95%CI:1.24-5.12) and
      TF (AHR: 2.19; 95%CI:1.13-4.22). CONCLUSIONS: Only 35.3% had access to HCV
      treatment. Despite excellent rates of SVR12 rates (91.6%), only 21% (545/2,607)
      of our HIV-HCV co-infected patients are cured.

PMID- 28520750
TI  - Awareness and trust of the FDA and CDC: Results from a national sample of US
      adults and adolescents.
AB  - Trust in government agencies plays a key role in advancing these organizations'
      agendas, influencing behaviors, and effectively implementing policies. However,
      few studies have examined the extent to which individuals are aware of and trust
      the leading United States agencies devoted to protecting the public's health.
      Using two national samples of adolescents (N = 1,125) and adults (N = 5,014), we
      examined demographic factors, with a focus on vulnerable groups, as correlates of
      awareness of and trust in the Centers for Disease Control and Prevention (CDC),
      Food and Drug Administration (FDA), and the federal government. From nine
      different weighted and adjusted logistic regression models, we found high levels
      of awareness of the existence of the FDA and CDC (ranging from 55.7% for
      adolescents' awareness of the CDC to 94.3% for adults' awareness of the FDA) and
      moderate levels of trust (ranging from a low of 41.8% for adults' trust in the
      federal government and a high of 78.8% for adolescents' trust of the FDA). In the
      adolescent and adult samples, awareness was higher among non-Hispanic Blacks and
      respondents with low numeracy. With respect to trust, few consistent demographic
      differences emerged. Our findings provide novel insights regarding awareness and
      trust in the federal government and specific United States public health
      agencies. Our findings suggest groups to whom these agencies may want to
      selectively communicate to enhance trust and thus facilitate their communication
      and regulatory agendas.

PMID- 28520751
TI  - "Do it-yourself": Home blood pressure as a predictor of traditional and everyday
      cognition in older adults.
AB  - BACKGROUND: Hypertension guidelines recommend home blood pressure (HBP)
      monitoring in adjunct to office blood pressure (OBP) for its greater
      reproducibility and prognostic utility in the prevention of cardiovascular
      outcomes, especially stroke. To date, the relationship between HBP and cognitive
      function remains unexplored. METHODS: We examined HBP as a cognitive predictor in
      a multi-ethnic group of community-dwelling adults aged 60 and over (N = 133)
      using neuropsychological measures and analyzed the data using multiple regression
      analyses. We also employed "everyday cognition" measures that have been found to
      have higher prognostic utility for real-world functioning than traditional
      cognitive tasks. RESULTS: Good to perfect HBP monitoring compliance over seven
      days was achieved by 88.7% of the participants with superior reliability
      (ICC>=.96) to office readings. Higher home systolic BP and pulse pressure
      predicted worse processing speed, executive function, and everyday cognitive
      function, whereas lower home diastolic BP predicted worse everyday cognition.
      Office readings were similarly associated with everyday cognitive function but
      with no other cognitive measures. CONCLUSION: Our findings are the first to
      validate HBP as a predictor of neuropsychological function in older adults beyond
      cognitive screening. Differential relationships among blood pressure variables
      and specific cognitive domains were observed. With proper standardization and
      training, we demonstrated that HBP can be obtained in a multi-ethnic community
      dwelling older adult cohort. Our findings emphasize the importance of employing
      blood pressure and cognitive measures that are adequately sensitive to detect
      vascular-related cognitive impairment in a relatively healthy population.
      Implications regarding proper HBP measurement for hypertension management,
      cognitive health, and everyday function are discussed.

PMID- 28520752
TI  - Antimicrobial peptides extend lifespan in Drosophila.
AB  - Antimicrobial peptides (AMPs) are important defense molecules of the innate
      immune system. High levels of AMPs are induced in response to infections to fight
      pathogens, whereas moderate levels induced by metabolic stress are thought to
      shape commensal microbial communities at barrier tissues. We expressed single
      AMPs in adult flies either ubiquitously or in the gut by using the inducible
      GeneSwitch system to tightly regulate AMP expression. We found that activation of
      single AMPs, including Drosocin, resulted in a significant extension of
      Drosophila lifespan. These animals showed reduced activity of immune pathways
      over lifetime, less intestinal regenerative processes, reduced stress response
      and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin
      induction protected the animals against infections with the natural Drosophila
      pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented
      the lifespan extending effect of Drosocin. Our study provides new insights into
      the crosstalk of innate immunity, intestinal homeostasis and ageing.

PMID- 28520753
TI  - Comparative accuracy of CT perfusion in diagnosing acute ischemic stroke: A
      systematic review of 27 trials.
AB  - OBJECTIVE: To systematically evaluate and compare the diagnostic accuracy of CT
      perfusion (CTP), non-enhanced computed tomography (NCCT) and computed tomography
      angiography (CTA) in detecting acute ischemic stroke. METHODS: We searched seven
      databases and screened the reference lists of the included studies. The risk of
      bias in the study quality was assessed using QUADASII. We produced paired forest
      plots in RevMan to show the variation of the sensitivity and specificity
      estimates together with their 95% CI. We used a hierarchical summary ROC model to
      summarize the sensitivity and specificity of CTP in detecting ischemic stroke.
      RESULTS: We identified 27 studies with a total of 2168 patients. The pooled
      sensitivity of CTP for acute ischemic stroke was 82% (95% CI 75-88%), and the
      specificity was 96% (95% CI 89-99%). CTP was more sensitive than NCCT and had a
      similar accuracy with CTA. There were no statistically significant differences in
      the sensitivity and specificity between patients who underwent CTP within 6 hours
      of symptom onset and beyond 6 hours after symptom onset. No adverse events were
      reported in the included studies. CONCLUSIONS: CTP is more accurate than NCCT and
      has similar accuracy to CTA in detecting acute ischemic stroke. However, the
      evidence is not strong. There is potential benefit of using CTP to select stroke
      patients for treatment, but more high-quality evidence is needed to confirm this
      result.

PMID- 28520754
TI  - Effects of milk product intake on thigh muscle strength and NFKB gene methylation
      during home-based interval walking training in older women: A randomized,
      controlled pilot study.
AB  - BACKGROUND: Muscle atrophy with aging is closely associated with chronic systemic
      inflammation and lifestyle-related diseases. In the present study, we assessed
      whether post-exercise milk product intake during 5-month interval walking
      training (IWT) enhanced the increase in thigh muscle strength and ameliorated
      susceptibility to inflammation in older women. METHODS: Subjects [n = 37, 66+/-5
      (standard deviation) yrs] who had been performing IWT for >6 months participated
      in this study. They were randomly divided into the following 3 groups: IWT alone
      (CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g
      protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product
      intake than the LD group (HD, n = 13). They were instructed to repeat >=5 sets of
      fast and slow walking for 3 min each at >=70% and 40% peak aerobic capacity for
      walking, respectively, per day for >=4 days/week. RESULTS: After IWT, thigh
      muscle strength increased in the HD group (8+/-2%) more than in the CNT group (
      2+/-3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15).
      Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and
      NFKB2, master genes of inflammation, was enhanced in the HD group (29+/-7% and
      44+/-11%, respectively) more than in the CNT group (-20+/-6% and -10+/-6%,
      respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed
      that several inflammation-related genes were hyper-methylated in the HD group
      compared with that in the CNT group, suggesting greater pro-inflammatory cytokine
      gene suppression in the HD group. CONCLUSION: HD milk product intake after
      exercise produced a greater percent increase in thigh muscle strength and NFKB1
      and NFKB2 gene methylation during IWT in physically active older women. TRIAL
      REGISTRATION: UMIN-CTR No. UMIN000024544 and No. UMIN000024912.

PMID- 28520755
TI  - Neuropsychological characteristics of Gulf War illness: A meta-analysis.
AB  - OBJECTIVE: Gulf War illness (GWI) is a disorder related to military service in
      the 1991 GW. Prominent symptoms include fatigue, pain and cognitive problems.
      These symptoms were reported by GW Veterans (GWV) immediately after the war and
      were eventually incorporated into case definitions of GWI. Neuropsychological
      function in GW veterans has been studied both among deployed GWV and in GWV
      diagnosed with GWI. Results have been inconsistent between and across GW
      populations. The purpose of the present investigation was to better characterize
      neuropsychological function in this veteran population. METHODS: Meta-analysis
      techniques were applied to published studies on neuropsychological performance in
      GWV to identify domains of dysfunction in deployed vs. non-deployed GW-era
      veterans and symptomatic vs. non-symptomatic GWVs. RESULTS: Significantly
      decreased performance was found in three functional domains: attention and
      executive function, visuospatial skills and learning/memory. CONCLUSIONS: These
      findings document the cognitive decrements associated with GW service, validate
      current GWI case definitions using cognitive criteria, and identify test measures
      for use in GWI research assessing GWI treatment trial efficacy.

PMID- 28520757
TI  - Predicting above-ground density and distribution of small mammal prey species at
      large spatial scales.
AB  - Grassland and shrub-steppe ecosystems are increasingly threatened by
      anthropogenic activities. Loss of native habitats may negatively impact important
      small mammal prey species. Little information, however, is available on the
      impact of habitat variability on density of small mammal prey species at broad
      spatial scales. We examined the relationship between small mammal density and
      remotely-sensed environmental covariates in shrub-steppe and grassland ecosystems
      in Wyoming, USA. We sampled four sciurid and leporid species groups using line
      transect methods, and used hierarchical distance-sampling to model density in
      response to variation in vegetation, climate, topographic, and anthropogenic
      variables, while accounting for variation in detection probability. We created
      spatial predictions of each species' density and distribution. Sciurid and
      leporid species exhibited mixed responses to vegetation, such that changes to
      native habitat will likely affect prey species differently. Density of white
      tailed prairie dogs (Cynomys leucurus), Wyoming ground squirrels (Urocitellus
      elegans), and leporids correlated negatively with proportion of shrub or
      sagebrush cover and positively with herbaceous cover or bare ground, whereas
      least chipmunks showed a positive correlation with shrub cover and a negative
      correlation with herbaceous cover. Spatial predictions from our models provide a
      landscape-scale metric of above-ground prey density, which will facilitate the
      development of conservation plans for these taxa and their predators at spatial
      scales relevant to management.

PMID- 28520756
TI  - De novo assembly and comparative transcriptome analysis of the foot from Chinese
      green mussel (Perna viridis) in response to cadmium stimulation.
AB  - The Chinese green mussel, Perna viridis, is a marine bivalve with important
      economic values as well as biomonitoring roles for aquatic pollution. Byssus,
      secreted by the foot gland, has been proved to bind heavy metals effectively. In
      this study, using the RNA sequencing technology, we performed comparative
      transcriptomic analysis on the mussel feet with or without inducing by cadmium
      (Cd). Our current work is aiming at providing insights into the molecular
      mechanisms of byssus binding to heavy metal ions. The transcriptome sequencing
      generated a total of 26.13-Gb raw data. After a careful assembly of clean data,
      we obtained a primary set of 105,127 unigenes, in which 32,268 unigenes were
      annotated. Based on the expression profiles, we identified 9,048 differentially
      expressed genes (DEGs) between Cd treatment (50 or 100 MUg/L) at 48 h and the
      control, suggesting an extensive transcriptome response of the mussels during the
      Cd stimulation. Moreover, we observed that the expression levels of 54 byssus
      protein coding genes increased significantly after the 48-h Cd stimulation. In
      addition, 16 critical byssus protein coding genes were picked for profiling by
      quantitative real-time PCR (qRT-PCR). Finally, we reached a primary conclusion
      that high content of tyrosine (Tyr), cysteine (Cys), histidine (His) residues or
      the special motif plays an important role in the accumulation of heavy metals in
      byssus. We also proposed an interesting model for the confirmed byssal Cd
      accumulation, in which biosynthesis of byssus proteins may play simultaneously
      critical roles since their transcription levels were significantly elevated.

PMID- 28520759
TI  - First evidence of the Hepatitis E virus in environmental waters in Colombia.
AB  - Hepatitis E virus (HEV) is one of the main causes of acute viral hepatitis of
      enteric transmission. HEV has been detected in environmental samples in several
      countries from Europe and Asia, constituting a risk factor for waterborne
      infection. In Colombia, HEV has been identified in samples obtained from patients
      as well as from swine, but no environmental studies have been carried out. To
      determine if HEV is present in environmental waters, samples from the main source
      of drinking water plant and of wastewater system of eight municipalities and two
      villages of Antioquia state (North West Colombia), were collected between
      December 2012 and April 2014. The HEV genome was detected by RT-PCR in 23.3%
      (7/30) of the samples from the main source of drinking water plants and in 16.7%
      (5/30) from sewage. Viral concentrates obtained from three positive sewage
      samples were used to inoculate HepG2 cell cultures that were followed for one
      month; however, the viral genome was not detected in any cell culture. This study
      demonstrates the circulation of HEV in both source of drinking water plants and
      wastewater in Antioquia state, Colombia. The presence of HEV in environmental
      waters could be a risk for waterborne transmission in this population. The
      findings of the present study, together with the evidence of HEV circulation in
      human and swine in Colombia, should be consider by public health authorities for
      the development of surveillance programs and the inclusion of HEV infection
      diagnosis in the guidelines of viral hepatitis in the country. This is the first
      report of HEV in environmental samples in Colombia and the second one in Latin
      America.

PMID- 28520758
TI  - Cumulative family risks across income levels predict deterioration of children's
      general health during childhood and adolescence.
AB  - Family is considered an important agent in the health development of children.
      This process is significant but quite complex because the prevalence of potential
      risk factors in the family can hinder children's health. This study examined if
      multiple family risks might have cumulative effect on children and youth's health
      across various levels of household income. The data in this study were drawn from
      the 2011-2012 U.S. National Survey of Children's Health (N = 79,601). A
      cumulative family risk (CFR) index was developed, which included such constructs
      as single-parenthood, unstable employment, large family, parenting stress, poor
      maternal education, poor maternal general health and poor maternal mental health.
      Multiple logistic regression analyses showed that CFR level was significantly
      related to children and youth's poor health outcome (p < .001). When poverty
      levels were considered, however, the impact of CFRs on children and youth's
      health was attenuated. The impact of CFRs was higher on children and youth from
      affluent families than on those from poor families. Overall there was a
      consistent pattern of trend in the point estimate as well as confidence limits as
      levels of affluence and numbers of family risk increased although some of the
      confidence intervals overlapped. Living in disadvantaged families might serve as
      a protective factor against CFRs possibly through repeated exposure to hardships
      and subsequent formation of resilience among some of the disadvantaged children.

PMID- 28520761
TI  - Antibiotic use in South Korea from 2007 to 2014: A health insurance database
      generated time series analysis.
AB  - BACKGROUND: Inappropriate antibiotic use significantly contributes to antibiotic
      resistance, resulting in reduced antibiotic efficacy and increasing physical
      burden and cost of disease. The goal of this study was to explore antibiotic
      usage patterns in South Korea using 2007-2014 health insurance claims data.
      METHODS: We used the Health Insurance Review & Assessment Service data, which
      represents nearly the entire population of South Korea, to discern patterns in
      antibiotic prescribing practices. The daily dose, as defined by the World Health
      Organization ([defined daily doses]/1000 inhabitants/day, [DID]), was used as a
      measure of antibiotic use. Subgroup analyses were performed on the basis of
      patient characteristics (sex, age, and disease) and provider characteristics
      (type of medical institution). RESULTS: Antibiotic use in DID increased from 23.5
      in 2007 to 27.7 in 2014. The <= 6 years old age group showed the highest level of
      usage at 59.21 DID in 2014, and showed an increasing trend each year. DIDs of
      beta-lactam antibacterials, penicillins (J01C), other beta-lactam antibacterials
      (J01D), lincosamides and streptogramins (J01F), quinolone antibacterials (J01M),
      and other antibacterials (J01X) increased over time. CONCLUSION: This study
      provides valuable statistics regarding antibiotic usage in South Korea; this is
      important for guiding health policy with regard to antibiotic usage. There is a
      need for further study exploring antibiotics use and resistance.

PMID- 28520760
TI  - Transcriptome profiling of ontogeny in the acridid grasshopper Chorthippus
      biguttulus.
AB  - Acridid grasshoppers (Orthoptera:Acrididae) are widely used model organisms for
      developmental, evolutionary, and neurobiological research. Although there has
      been recent influx of orthopteran transcriptomic resources, many use pooled
      ontogenetic stages obscuring information about changes in gene expression during
      development. Here we developed a de novo transcriptome spanning 7 stages in the
      life cycle of the acridid grasshopper Chorthippus biguttulus. Samples from
      different stages encompassing embryonic development through adults were used for
      transcriptomic profiling, revealing patterns of differential gene expression that
      highlight processes in the different life stages. These patterns were validated
      with semi-quantitative RT-PCR. Embryonic development showed a strongly
      differentiated expression pattern compared to all of the other stages and genes
      upregulated in this stage were involved in signaling, cellular differentiation,
      and organ development. Our study is one of the first to examine gene expression
      during post-embryonic development in a hemimetabolous insect and we found that
      only the fourth and fifth instars had clusters of genes upregulated during these
      stages. These genes are involved in various processes ranging from synthesis of
      biogenic amines to chitin binding. These observations indicate that post
      embryonic ontogeny is not a continuous process and that some instars are
      differentiated. Finally, genes upregulated in the imago were generally involved
      in aging and immunity. Our study highlights the importance of looking at ontogeny
      as a whole and indicates promising directions for future research in orthopteran
      development.

PMID- 28520762
TI  - Indexical and linguistic processing by 12-month-olds: Discrimination of speaker,
      accent and vowel differences.
AB  - Infants preferentially discriminate between speech tokens that cross native
      category boundaries prior to acquiring a large receptive vocabulary, implying a
      major role for unsupervised distributional learning strategies in phoneme
      acquisition in the first year of life. Multiple sources of between-speaker
      variability contribute to children's language input and thus complicate the
      problem of distributional learning. Adults resolve this type of indexical
      variability by adjusting their speech processing for individual speakers. For
      infants to handle indexical variation in the same way, they must be sensitive to
      both linguistic and indexical cues. To assess infants' sensitivity to and
      relative weighting of indexical and linguistic cues, we familiarized 12-month-old
      infants to tokens of a vowel produced by one speaker, and tested their listening
      preference to trials containing a vowel category change produced by the same
      speaker (linguistic information), and the same vowel category produced by another
      speaker of the same or a different accent (indexical information). Infants
      noticed linguistic and indexical differences, suggesting that both are salient in
      infant speech processing. Future research should explore how infants weight these
      cues in a distributional learning context that contains both phonetic and
      indexical variation.

PMID- 28520763
TI  - Genome-wide gene expression array identifies novel genes related to disease
      severity and excessive daytime sleepiness in patients with obstructive sleep
      apnea.
AB  - We aimed to identify novel molecular associations between chronic intermittent
      hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea
      (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells
      from 48 patients with sleep-disordered breathing stratified into four groups:
      primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and
      very severe OSA patients on long-term continuous positive airway pressure
      treatment (VSOC). Comparisons of the microarray gene expression data identified
      eight genes up-regulated with OSA and down-regulated with CPAP treatment, and
      five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein
      expression levels of two genes related to endothelial tight junction (AMOT P130,
      and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1
      P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was
      further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the
      VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was
      increased in OSA patients with excessive daytime sleepiness, BIRC3 protein
      expression was decreased in OSA patients with hypertension, and LGALS3 protein
      expression was increased in OSA patients with chronic kidney disease. In vitro
      short-term intermittent hypoxia with re-oxygenation experiment showed immediate
      over-expression of ADAR1 P150. In conclusion, we identified a novel association
      between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index
      in OSA patients. AMOT and GALIG may constitute an important determinant for the
      development of hypersomnia and kidney injury, respectively, while BIRC3 may play
      a protective role in the development of hypertension.

PMID- 28520764
TI  - Rib biomechanical properties exhibit diagnostic potential for accurate ageing in
      forensic investigations.
AB  - Age estimation remains one of the most challenging tasks in forensic practice
      when establishing a biological profile of unknown skeletonised remains.
      Morphological methods based on developmental markers of bones can provide
      accurate age estimates at a young age, but become highly unreliable for ages over
      35 when all developmental markers disappear. This study explores the changes in
      the biomechanical properties of bone tissue and matrix, which continue to change
      with age even after skeletal maturity, and their potential value for age
      estimation. As a proof of concept we investigated the relationship of 28
      variables at the macroscopic and microscopic level in rib autopsy samples from 24
      individuals. Stepwise regression analysis produced a number of equations one of
      which with seven variables showed an R2 = 0.949; a mean residual error of 2.13
      yrs +/-0.4 (SD) and a maximum residual error value of 2.88 yrs. For forensic
      purposes, by using only bench top machines in tests which can be carried out
      within 36 hrs, a set of just 3 variables produced an equation with an R2 = 0.902
      a mean residual error of 3.38 yrs +/-2.6 (SD) and a maximum observed residual
      error 9.26yrs. This method outstrips all existing age-at-death methods based on
      ribs, thus providing a novel lab based accurate tool in the forensic
      investigation of human remains. The present application is optimised for fresh
      (uncompromised by taphonomic conditions) remains, but the potential of the
      principle and method is vast once the trends of the biomechanical variables are
      established for other environmental conditions and circumstances.

PMID- 28520765
TI  - An integrative analysis of tissue-specific transcriptomic and metabolomic
      responses to short-term dietary methionine restriction in mice.
AB  - Dietary methionine restriction (MR) produces a coordinated series of
      transcriptional responses in peripheral tissues that limit fat accretion, remodel
      lipid metabolism in liver and adipose tissue, and improve overall insulin
      sensitivity. Hepatic sensing of reduced methionine leads to induction and release
      of fibroblast growth factor 21 (FGF21), which acts centrally to increase
      sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has
      direct effects in adipose to enhance glucose uptake and oxidation. However, an
      understanding of how the liver senses and translates reduced dietary methionine
      into these transcriptional programs remains elusive. A comprehensive systems
      biology approach integrating transcriptomic and metabolomic readouts in MR
      treated mice confirmed that three interconnected mechanisms (fatty acid transport
      and oxidation, tricarboxylic acid cycle, and oxidative phosphorylation) were
      activated in MR-treated inguinal adipose tissue. In contrast, the effects of MR
      in liver involved up-regulation of anti-oxidant responses driven by the nuclear
      factor, erythroid 2 like 2 transcription factor, NFE2L2. Metabolomic analysis
      provided evidence for redox imbalance, stemming from large reductions in the
      master anti-oxidant molecule glutathione coupled with disproportionate increases
      in ophthalmate and its precursors, glutamate and 2-aminobutyrate. Thus, cysteine
      and its downstream product, glutathione, emerge as key early hepatic signaling
      molecules linking dietary MR to its metabolic phenotype.

PMID- 28520767
TI  - MS26/CYP704B is required for anther and pollen wall development in bread wheat
      (Triticum aestivum L.) and combining mutations in all three homeologs causes male
      sterility.
AB  - Development of anthers and pollen represents an important aspect of the life
      cycle in flowering plants. Genes contributing to anther and pollen development
      have been widely studied in many plant species. Ms26/CYP704B genes play an
      important role in pollen development through biosynthesis of sporopollenin for
      pollen exine formation. To investigate the role of Ms26/CYP704B genes in anther
      and pollen development of bread wheat, mutations in the A-, B-, and D-homeologs
      of the putative Ms26/CYP704B gene were analyzed. Single and double homozygous
      mutants in any of the homeologs did not affect pollen development and male
      fertility. Triple homozygous mutants resulted in completely male sterile plants
      that were defective in pollen and anther development. Additionally, double
      homozygous-single heterozygous mutants were also male sterile although with
      varying levels of residual fertility. The fertility of these triple mutants was
      dependent upon the homeolog contributing the wild-type allele. Two heterologous
      Ms26/CYP704B genes, when transformed into a triple homozygous mutant background,
      completely restored male fertility, whereas a single gene was unable to restore
      fertility. Functional analysis of Ms26/CYP704B furthers the understanding of male
      fertility genes which can be utilized for the development of novel hybrid seed
      production systems in wheat.

PMID- 28520766
TI  - Transcriptomic analysis of salt stress responsive genes in Rhazya stricta.
AB  - Rhazya stricta is an evergreen shrub that is widely distributed across Western
      and South Asia, and like many other members of the Apocynaceae produces
      monoterpene indole alkaloids that have anti-cancer properties. This species is
      adapted to very harsh desert conditions making it an excellent system for
      studying tolerance to high temperatures and salinity. RNA-Seq analysis was
      performed on R. stricta exposed to severe salt stress (500 mM NaCl) across four
      time intervals (0, 2, 12 and 24 h) to examine mechanisms of salt tolerance. A
      large number of transcripts including genes encoding tetrapyrroles and
      pentatricopeptide repeat (PPR) proteins were regulated only after 12 h of stress
      of seedlings grown in controlled greenhouse conditions. Mechanisms of salt
      tolerance in R. stricta may involve the upregulation of genes encoding chaperone
      protein Dnaj6, UDP-glucosyl transferase 85a2, protein transparent testa 12 and
      respiratory burst oxidase homolog protein b. Many of the highly-expressed genes
      act on protecting protein folding during salt stress and the production of
      flavonoids, key secondary metabolites in stress tolerance. Other regulated genes
      encode enzymes in the porphyrin and chlorophyll metabolic pathway with important
      roles during plant growth, photosynthesis, hormone signaling and abiotic
      responses. Heme biosynthesis in R. stricta leaves might add to the level of salt
      stress tolerance by maintaining appropriate levels of photosynthesis and normal
      plant growth as well as by the participation in reactive oxygen species (ROS)
      production under stress. We speculate that the high expression levels of PPR
      genes may be dependent on expression levels of their targeted editing genes.
      Although the results of PPR gene family indicated regulation of a large number of
      transcripts under salt stress, PPR actions were independent of the salt stress
      because their RNA editing patterns were unchanged.

PMID- 28520768
TI  - Mobile phone reminders and peer counseling improve adherence and treatment
      outcomes of patients on ART in Malaysia: A randomized clinical trial.
AB  - BACKGROUND: Adherence to treatment remains the cornerstone of long term viral
      suppression and successful treatment outcomes among patients receiving
      Antiretroviral Therapy (ART). OBJECTIVE(S): Evaluate the effectiveness of mobile
      phone reminders and peer counseling in improving adherence and treatment outcomes
      among HIV positive patients on ART in Malaysia. METHODS: A single-blind, parallel
      group RCT conducted in Hospital Sungai Buloh, Malaysia in which 242 adult
      Malaysian patients were randomized to intervention or control groups.
      Intervention consisted of a reminder module delivered through SMS and telephone
      call reminders by trained research assistants for 24 consecutive weeks (starting
      from date of ART initiation), in addition to adherence counseling at every clinic
      visit. The length of intended follow up for each patient was 6 months. Data on
      adherence behavior of patients was collected using specialized, pre-validated
      Adult AIDS Clinical Trial Group (AACTG) adherence questionnaires. Data on weight,
      clinical symptoms, CD4 count and viral load tests were also collected. Data was
      analyzed using SPSS version 22 and R software. Repeated measures ANOVA,
      Friedman's ANOVA and Multivariate regression models were used to evaluate
      efficacy of the intervention. RESULTS: The response rate after 6 months follow up
      was 93%. There were no significant differences at baseline in gender, employment
      status, income distribution and residential location of respondents between the
      intervention and control group. After 6 months follow up, the mean adherence was
      significantly higher in the intervention group (95.7; 95% CI: 94.39-96.97) as
      compared to the control group (87.5; 95% CI: 86.14-88.81). The proportion of
      respondents who had Good (>95%) adherence was significantly higher in the
      intervention group (92.2%) compared to the control group (54.6%). A significantly
      lower frequency in missed appointments (14.0% vs 35.5%) (p = 0.001), lower viral
      load (p = 0.001), higher rise in CD4 count (p = 0.017), lower incidence of
      tuberculosis (p = 0.001) and OIs (p = 0.001) at 6 months follow up, was observed
      among patients in the intervention group. CONCLUSION: Mobile phone reminders (SMS
      and telephone call reminders) and peer counseling are effective in improving
      adherence and treatment outcomes among HIV positive patients on ART in Malaysia.
      These findings may be of potential benefit for collaborative adherence planning
      between patients and health care providers at ART commencement.

PMID- 28520769
TI  - Optimal method for assessment of respiratory muscle strength in neuromuscular
      disorders using sniff nasal inspiratory pressure (SNIP).
AB  - BACKGROUND: The ability to accurately determine respiratory muscle strength is
      vitally important in patients with neuromuscular disorders (NMD). Sniff nasal
      inspiratory pressure (SNIP), a test of inspiratory muscle strength, is easier to
      perform for many NMD patients than the more commonly used determination of
      maximum inspiratory pressure measured at the mouth (MIP). However, due to an
      inconsistent approach in the literature, the optimal technique to perform the
      SNIP maneuver is unclear. Therefore, we systematically evaluated the impact of
      performing the maneuver with nostril contralateral to the pressure-sensing probe
      open (SNIPOP) versus closed (SNIPCL), on determination of inspiratory muscle
      strength in NMD patients as well as control subjects with normal respiratory
      muscle function. METHODS: NMD patients (n = 52) and control subjects without
      respiratory dysfunction (n = 52) were studied. SNIPOP, SNIPCL, and MIP were
      measured during the same session and compared using ANOVA. Agreement and bias
      were assessed with intraclass correlation coefficients (ICC) and Bland-Altman
      plots. RESULTS: Mean MIP values were 58.2 and 94.0 cmH2O in NMD and control
      subjects, respectively (p<0.001). SNIPCL was greater than SNIPOP in NMD (51.9 +/
      31.0 vs. 36.9 +/-25.4 cmH2O; p<0.001) as well as in controls (89.2 +/-28.1 vs.
      69.2 +/-29.2 cmH2O; p<0.001). In both populations, the ICC between MIP and SNIPCL
      (NMD = 0.78, controls = 0.35) was higher than for MIP and SNIPOP (NMD = 0.53,
      controls = 0.06). In addition, SNIPCL was more often able to exclude inspiratory
      muscle weakness than SNIPOP. CONCLUSIONS: SNIPCL values are systematically higher
      than SNIPOP in both normal subjects and NMD patients. Therefore, SNIPCL is a
      useful complementary test for ruling out inspiratory muscle weakness in
      individuals with low MIP values.

PMID- 28520770
TI  - Life history trade-off moderates model predictions of diversity loss from climate
      change.
AB  - Climate change can trigger species range shifts, local extinctions and changes in
      diversity. Species interactions and dispersal capacity are important mediators of
      community responses to climate change. The interaction between multispecies
      competition and variation in dispersal capacity has recently been shown to
      exacerbate the effects of climate change on diversity and to increase predictions
      of extinction risk dramatically. Dispersal capacity, however, is part of a
      species' overall ecological strategy and are likely to trade off with other
      aspects of its life history that influence population growth and persistence. In
      plants, a well-known example is the trade-off between seed mass and seed number.
      The presence of such a trade-off might buffer the diversity loss predicted by
      models with random but neutral (i.e. not impacting fitness otherwise) differences
      in dispersal capacity. Using a trait-based metacommunity model along a warming
      climatic gradient the effect of three different dispersal scenarios on model
      predictions of diversity change were compared. Adding random variation in species
      dispersal capacity caused extinctions by the introduction of strong fitness
      differences due an inherent property of the dispersal kernel. Simulations
      including a fitness-equalising trade-off based on empirical relationships between
      seed mass (here affecting dispersal distance, establishment probability, and
      seedling biomass) and seed number (fecundity) maintained higher initial species
      diversity and predicted lower extinction risk and diversity loss during climate
      change than simulations with variable dispersal capacity. Large seeded species
      persisted during climate change, but developed lags behind their climate niche
      that may cause extinction debts. Small seeded species were more extinction-prone
      during climate change but tracked their niches through dispersal and
      colonisation, despite competitive resistance from residents. Life history trade
      offs involved in coexistence mechanisms may increase community resilience to
      future climate change and are useful guides for model development.

PMID- 28520771
TI  - Quality of maternity care and its determinants along the continuum in Kenya: A
      structural equation modeling analysis.
AB  - BACKGROUND: Improving access to delivery services does not guarantee access to
      quality obstetric care and better survival, and therefore, concerns for quality
      of maternal and newborn care in low- and middle-income countries have been
      raised. Our study explored characteristics associated with the quality of initial
      assessment, intrapartum, and immediate postpartum and newborn care, and further
      assessed the relationships along the continuum of care. METHODS: The 2010 Service
      Provision Assessment data of Kenya for 627 routine deliveries of women aged 15-49
      were used. Quality of care measures were assessed using recently validated
      quality of care measures during initial assessment, intrapartum, and postpartum
      periods. Data were analyzed with negative binomial regression and structural
      equation modeling technique. RESULTS: The negative binomial regression results
      identified a number of determinants of quality, such as the level of health
      facilities, managing authority, presence of delivery fee, central electricity
      supply and clinical guideline for maternal and neonatal care. Our structural
      equation modeling (SEM) further demonstrated that facility characteristics were
      important determinants of quality for initial assessment and postpartum care,
      while characteristics at the provider level became more important in shaping the
      quality of intrapartum care. Furthermore we also noted that quality of initial
      assessment had a positive association with quality of intrapartum care (beta =
      0.71, p < 0.001), which in turn was positively associated with the quality of
      newborn and immediate postpartum care (beta = 1.29, p = 0.004). CONCLUSIONS: A
      continued focus on quality of care along the continuum of maternity care is
      important not only to mothers but also their newborns. Policymakers should
      therefore ensure that required resources, as well as adequate supervision and
      emphasis on the quality of obstetric care, are available.

PMID- 28520772
TI  - The chicken embryo as an efficient model to test the function of muscle fusion
      genes in amniotes.
AB  - The fusion of myoblasts into multinucleated myotubes is a crucial step of muscle
      growth during development and of muscle repair in the adult. While multiple genes
      were shown to play a role in this process, a vertebrate model where novel
      candidates can be tested and analyzed at high throughput and relative ease has
      been lacking. Here, we show that the early chicken embryo is a fast and robust
      model in which functional testing of muscle fusion candidate genes can be
      performed. We have used known modulators of muscle fusion, Rac1 and Cdc42, along
      with the in vivo electroporation of integrated, inducible vectors, to show that
      the chicken embryo is a suitable model in which their function can be tested and
      quantified. In addition to nuclei content, specific characteristics of the
      experimental model allow a fine characterization of additional morphological
      features that are nearly impossible to assess in other model organisms. This
      study should establish the chicken embryo as a cheap, reliable and powerful model
      in which novel vertebrate muscle fusion candidates can be evaluated.

PMID- 28520773
TI  - Development of the "Highly Sensitive Dog" questionnaire to evaluate the
      personality dimension "Sensory Processing Sensitivity" in dogs.
AB  - In humans, the personality dimension 'sensory processing sensitivity (SPS)', also
      referred to as "high sensitivity", involves deeper processing of sensory
      information, which can be associated with physiological and behavioral
      overarousal. However, it has not been studied up to now whether this dimension
      also exists in other species. SPS can influence how people perceive the
      environment and how this affects them, thus a similar dimension in animals would
      be highly relevant with respect to animal welfare. We therefore explored whether
      SPS translates to dogs, one of the primary model species in personality research.
      A 32-item questionnaire to assess the "highly sensitive dog score" (HSD-s) was
      developed based on the "highly sensitive person" (HSP) questionnaire. A large
      scale, international online survey was conducted, including the HSD
      questionnaire, as well as questions on fearfulness, neuroticism, "demographic"
      (e.g. dog sex, age, weight; age at adoption, etc.) and "human" factors (e.g.
      owner age, sex, profession, communication style, etc.), and the HSP
      questionnaire. Data were analyzed using linear mixed effect models with forward
      stepwise selection to test prediction of HSD-s by the above-mentioned factors,
      with country of residence and dog breed treated as random effects. A total of
      3647 questionnaires were fully completed. HSD-, fearfulness, neuroticism and HSP
      scores showed good internal consistencies, and HSD-s only moderately correlated
      with fearfulness and neuroticism scores, paralleling previous findings in humans.
      Intra- (N = 447) and inter-rater (N = 120) reliabilities were good. Demographic
      and human factors, including HSP score, explained only a small amount of the
      variance of HSD-s. A PCA analysis identified three subtraits of SPS, comparable
      to human findings. Overall, the measured personality dimension in dogs showed
      good internal consistency, partial independence from fearfulness and neuroticism,
      and good intra- and inter-rater reliability, indicating good construct validity
      of the HSD questionnaire. Human and demographic factors only marginally affected
      the HSD-s suggesting that, as hypothesized for human SPS, a genetic basis may
      underlie this dimension within the dog species.

PMID- 28520774
TI  - Affective responses in mountain hiking-A randomized crossover trial focusing on
      differences between indoor and outdoor activity.
AB  - INTRODUCTION: Affective responses during physical activity (PA) are important for
      engagement in PA programs and for adherence to a physically active lifestyle.
      Little is known about the affective responses to PA bouts lasting longer than 45
      minutes. Therefore, the aims of the present study were to analyse acute effects
      on affective responses of a three-hour outdoor PA intervention (mountain hiking)
      compared to a sedentary control situation and to an indoor treadmill condition.
      METHODS: Using a randomized crossover design, 42 healthy participants were
      randomly exposed to three different conditions: outdoor mountain hiking, indoor
      treadmill walking, and sedentary control situation (approximately three hours
      each). Measures included the Feeling Scale, Felt Arousal Scale and a Mood Survey
      Scale. Repeated measures ANOVAs were used to analyse differences between the
      conditions. RESULTS: Compared to the control situation, the participants showed a
      significant increase in affective valence (d = 1.21, p < .001), activation (d =
      0.81, p = .004), elation (d = 1.07, p < .001), and calmness (d = 0.84, p = .004),
      and a significant decrease in fatigue (d = -1.19, p < .001) and anxiety (d = 
      .79, p < .001) after mountain hiking. Outdoor mountain hiking showed
      significantly greater positive effects on affective valence, activation, and
      fatigue compared to indoor treadmill walking. DISCUSSION: The results indicate
      that a three-hour PA intervention (mountain hiking) elicits higher positive and
      lower negative affective responses compared to a sedentary control situation and
      to an indoor PA condition. Outdoor mountain hiking can be recommended by health
      professionals as a form of PA with the potential to positively influence
      affective responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT02853760.
      https://clinicaltrials.gov/. Date of registration: 08/02/2016 (retrospectively
      registered). Date of enrolment of the first participant to the trial: 05/01/2014.

PMID- 28520775
TI  - Sex differences in neuromuscular androgen receptor expression and sociosexual
      behavior in a sex changing fish.
AB  - Androgen signaling, via receptor binding, is critical for regulating the
      physiological and morphological foundations of male-typical reproductive behavior
      in vertebrates. Muscles essential for male courtship behavior and copulation are
      highly sensitive to androgens. Differences in the distribution and density of the
      androgen receptor (AR) are important for maintaining dimorphic musculature and
      thus may provide for anatomical identification of sexually selected traits. In
      Lythrypnus dalli, a bi-directional hermaphroditic teleost fish, both sexes
      produce agonistic approach displays, but reproductive behavior is sexually
      dimorphic. The male-specific courtship behavior is characterized by rapid jerky
      movements (involving dorsal fin erection) towards a female or around their nest.
      Activation of the supracarinalis muscle is involved in dorsal fin contributions
      to both agonistic and sociosexual behavior in other fishes, suggesting that
      differences in goby sexual behavior may be reflected in sexual dimorphism in AR
      signaling in this muscle. We examined sex differences in the local distribution
      of AR in supracarinalis muscle and spinal cord. Our results demonstrate that
      males do express more AR in the supracarinalis muscle relative to females, but
      there was no sex difference in the number of spinal motoneurons expressing AR.
      Interestingly, AR expression in the supracarinalis muscle was also related to
      rates of sociosexual behavior in males, providing evidence that sexual selection
      may influence muscle androgenic sensitivity to enhance display vigor. Sex
      differences in the distribution and number of cells expressing AR in the
      supracarinalis muscle may underlie the expression of dimorphic behaviors in L.
      dalli.

PMID- 28520776
TI  - Proteomic analysis of tea plants (Camellia sinensis) with purple young shoots
      during leaf development.
AB  - Tea products made from purple leaves are highly preferred by consumers due to the
      health benefits. This study developed a proteome reference map related to color
      changes during leaf growth in tea (Camellia sinensis) plant with purple young
      shoots using two-dimensional electrophoresis (2-DE). Forty-six differentially
      expressed proteins were detected in the gel and successfully identified by using
      MALDI-TOF/TOF-MS. The pronounced changes in the proteomic profile between tender
      purple leaves (TPL) and mature green leaves (MGL) included: 1) the lower activity
      of proteins associated with CO2 assimilation, energy metabolism and photo flux
      efficiency and higher content of anthocyanins in TPL than those in MGL may
      protect tender leaves against photo-damage; 2) the higher abundance of chalcone
      synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS) likely
      contributes to the synthesis of anthocyanins, catechins and flavonols in TPL
      tissues; 3) higher abundance of stress response proteins, such as glutathione S
      transferases (GST) and phospholipid hydroperoxide glutathione peroxidase (PHGPx),
      could enhance the tolerance of TPL tissues to adverse condition in; and 4) the
      increased abundance of proteins related to protein synthesis, nucleic acids and
      cell wall proteins should be beneficial for the proliferation and expansion of
      leaf cell in TPL tissues. qPCR analysis showed that the expression of
      differentially abundant proteins was regulated at the transcriptional level.
      Therefore, the results indicated that higher abundance of CHI and CHS may account
      for the production of the purple-shoot phenotype in Wuyiqizhong 18 and thereby,
      enhancing the anthocyanin biosynthesis. The higher abundance of glutamine
      synthetase (GS) proteins related to the theanine biosynthesis may improve the
      flavor of tea products from TPL materials. Thus, this work should help to
      understand the molecular mechanisms underlying the changes in leaf color
      alteration.

PMID- 28520777
TI  - Network based stratification of major cancers by integrating somatic mutation and
      gene expression data.
AB  - The stratification of cancer into subtypes that are significantly associated with
      clinical outcomes is beneficial for targeted prognosis and treatment. In this
      study, we integrated somatic mutation and gene expression data to identify
      clusters of patients. In contrast to previous studies, we constructed cancer-type
      specific significant co-expression networks (SCNs) rather than using a fixed gene
      network across all cancers, such as the network-based stratification (NBS)
      method, which ignores cancer heterogeneity. For each type of cancer, the gene
      expression data were used to construct the SCN network, while the gene somatic
      mutation data were mapped onto the network, propagated, and used for further
      clustering. For the clustering, we adopted an improved network-regularized non
      negative matrix factorization (netNMF) (netNMF_HC) for a more precise
      classification. We applied our method to various datasets, including ovarian
      cancer (OV), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma
      (UCEC) cohorts derived from the TCGA (The Cancer Genome Atlas) project. Based on
      the results, we evaluated the performance of our method to identify survival
      relevant subtypes and further compared it to the NBS method, which adopts priori
      networks and netNMF algorithm. The proposed algorithm outperformed the NBS method
      in identifying informative cancer subtypes that were significantly associated
      with clinical outcomes in most cancer types we studied. In particular, our method
      identified survival-associated UCEC subtypes that were not identified by the NBS
      method. Our analysis indicated valid subtyping of patient could be applied by
      mutation data with cancer-type-specific SCNs and netNMF_HC for individual cancers
      because of specific cancer co-expression patterns and more precise clustering.

PMID- 28520778
TI  - Texture analysis using proton density and T2 relaxation in patients with
      histological usual interstitial pneumonia (UIP) or nonspecific interstitial
      pneumonia (NSIP).
AB  - OBJECTIVES: The purpose of our study was to assess proton density (PD) and T2
      relaxation time of usual interstitial pneumonia (UIP) and nonspecific
      interstitial pneumonia (NSIP) and to evaluate their utility in differentiating
      the two patterns. Furthermore, we aim to investigate whether these two parameters
      could help differentiate active-inflammatory and stable-fibrotic lesions in NSIP.
      METHODS: 32 patients (mean age: 69 years; M:F, 1:1) with pathologically proven
      disease (UIP:NSIP, 1:1), underwent thoracic thin-section multislice CT scan and
      1.5T MRI. A total of 437 regions-of-interest (ROIs) were classified at CT as
      advanced, moderate or mild alterations. Based on multi-echo single-shot TSE
      sequence acquired at five echo times, with breath-holding at end-expiration and
      ECG-triggering, entire lung T2 and PD maps were generated from each subject. The
      T2 relaxation time and the respective signal intensity were quantified by
      performing a ROI measurement on the T2 and PD maps in the corresponding CT
      selected areas of the lung. RESULTS: UIP and NSIP regional patterns could not be
      differentiated by T2 relaxation times or PD values alone. Overall, a strong
      positive correlation was found between T2 relaxation and PD in NSIP, r = 0.64,
      p<0.001; however, this correlation was weak in UIP, r = 0.20, p = 0.01. T2
      relaxation showed significant statistical difference between active-inflammatory
      and stable-fibrotic NSIP regions at all levels, p<0.05, while for the analysis of
      ventral lesions PD proved no statistical difference, p>0.05. CONCLUSIONS: T2
      relaxation times and PD values may provide helpful quantitative information for
      differentiating NSIP from UIP pattern. These parameters have the potential to
      differentiate active-inflammatory and stable-fibrotic lesions in NSIP.

PMID- 28520780
TI  - Towards a point-of-care strip test to diagnose sickle cell anemia.
AB  - A rapid test to identify patients with sickle cell disease could have important
      benefits in low-resource settings. Sickle cell anemia (SCA) affects about 300,000
      newborns each year, the majority of whom are born in sub-Saharan Africa. Low-cost
      therapies are available to treat SCA, but most countries in sub-Saharan Africa
      lack robust neonatal screening programs needed to identify patients in need of
      treatment. To address this need, we developed and evaluated a competitive lateral
      flow assay that identifies patients with SCA (genotype HbSS) in 15 minutes using
      undiluted whole blood. A small volume of blood (0.5 MUL- 3 MUL) is mixed with
      antibody-coated blue latex beads in a tube and applied to the strip. Strips are
      then placed in a well of running buffer and allowed to run for 10 minutes.
      Laboratory evaluation with samples containing different proportions of hemoglobin
      A (HbA) and hemoglobin S (HbS) indicated that the test should enable
      identification of SCA patients but not persons with sickle cell trait (SCT). We
      evaluated the test using 41 samples from individuals with SCA, SCT, and normal
      blood. With visual inspection or quantitative analysis, we found a 98% accuracy
      when differentiating SCA from normal and SCT samples as a group (90% sensitivity
      and 100% specificity for identifying SCA). This work demonstrates important steps
      towards making a lateral flow test for hemoglobinopathies more appropriate for
      point-of-care use; further work is needed before the test is appropriate for
      clinical use.

PMID- 28520779
TI  - Church attendance, allostatic load and mortality in middle aged adults.
AB  - IMPORTANCE: Religiosity has been associated with positive health outcomes.
      Hypothesized pathways for this association include religious practices, such as
      church attendance, that result in reduced stress. OBJECTIVE: The objective of
      this study was to examine the relationship between religiosity (church
      attendance), allostatic load (AL) (a physiologic measure of stress) and all-cause
      mortality in middle-aged adults. DESIGN, SETTING AND PARTICIPANTS: Data for this
      study are from NHANES III (1988-1994). The analytic sample (n = 5449) was
      restricted to adult participants, who were between 40-65 years of age at the time
      of interview, had values for at least 9 out of 10 clinical/biologic markers used
      to derive AL, and had complete information on church attendance. MAIN OUTCOMES
      AND MEASURES: The primary outcomes were AL and mortality. AL was derived from
      values for metabolic, cardiovascular, and nutritional/inflammatory
      clinical/biologic markers. Mortality was derived from a probabilistic algorithm
      matching the NHANES III Linked Mortality File to the National Death Index through
      December 31, 2006, providing up to 18 years follow-up. The primary predictor
      variable was baseline report of church attendance over the past 12 months. Cox
      proportional hazard logistic regression models contained key covariates including
      socioeconomic status, self-rated health, co-morbid medical conditions, social
      support, healthy eating, physical activity, and alcohol intake. RESULTS:
      Churchgoers (at least once a year) comprised 64.0% of the study cohort (n =
      3782). Non-churchgoers had significantly higher overall mean AL scores and higher
      prevalence of high-risk values for 3 of the 10 markers of AL than did
      churchgoers. In bivariate analyses non-churchgoers, compared to churchgoers, had
      higher odds of an AL score 2-3 (OR 1.24; 95% CI 1.01, 1.50) or >=4 (OR 1.38; 95%
      CI 1.11, 1.71) compared to AL score of 0-1. More frequent churchgoers (more than
      once a week) had a 55% reduction of all-cause mortality risk compared with non
      churchgoers. (HR 0.45, CI 0.24-0.85) in the fully adjusted model that included
      AL. CONCLUSIONS AND RELEVANCE: We found a significant association between church
      attendance and mortality among middle-aged adults after full adjustments. AL, a
      measure of stress, only partially explained differences in mortality between
      church and non-church attendees. These findings suggest a potential independent
      effect of church attendance on mortality.

PMID- 28520782
TI  - Adaptive double threshold energy detection based on Markov model for cognitive
      radio.
AB  - The rapid development in the area of cognitive radio technology leads the society
      to higher standards of spectrum sensing performance, particularly in low signal
      to-noise ratio (SNR) environment. This article proposes an adaptive double
      threshold energy sensing method based on Markov model (ADEMM). When using the
      double-threshold energy sensing method, the modified Markov model that accounts
      for the time varying characteristic of the channel occupancy was presented to
      resolve the 'confused' channel state. Furthermore, in order to overcome the
      effect of noise uncertainty, the findings of this article introduce an adaptive
      double-threshold spectrum sensing method that adjusts its thresholds according to
      the achievable maximal detection probability. Numerical simulations show that the
      proposed ADEMM achieves better detection performance than the conventional double
      threshold energy sensing schemes, especially in very low SNR region.

PMID- 28520781
TI  - Physical activity and sedentary behaviour in daily life: A comparative analysis
      of the Global Physical Activity Questionnaire (GPAQ) and the SenseWear armband.
AB  - Reduction of sedentary time and an increase in physical activity offer potential
      to improve public health. However, quantifying physical activity behaviour under
      real world conditions is a major challenge and no standard of good practice is
      available. Our aim was to compare the results of physical activity and sedentary
      behaviour obtained with a self-reported instrument (Global Physical Activity
      Questionnaire (GPAQ)) and a wearable sensor (SenseWear) in a repeated measures
      study design. Healthy adults (41 in Antwerp, 41 in Barcelona and 40 in London)
      wore the SenseWear armband for seven consecutive days and completed the GPAQ on
      the final day. This was repeated three times. We used the Wilcoxon signed rank
      sum test, Spearman correlation coefficients, mixed effects regression models and
      Bland-Altman plots to study agreement between both methods. Mixed models were
      used to assess the effect of personal characteristics on the absolute and
      relative difference between estimates obtained with the GPAQ and SenseWear.
      Moderate to vigorous energy expenditure and duration derived from the GPAQ were
      significantly lower (p<0.05) compared to the SenseWear, yet these variables
      showed significant correlations ranging from 0.45 to 0.64. Estimates of vigorous
      intensity physical activity in particular showed high similarity (r>0.59).
      Results for sedentary behaviour did not differ, yet were poorly correlated
      (r<0.25). The differences between all variables were reproducible across repeated
      measurements. In addition, we observed a relationship between these differences
      and BMI, body fat and physical activity domain. Due to the lack of a standardized
      protocol, results from different studies measuring physical activity and
      sedentary behaviour are difficult to compare. Therefore, we suggested an easy-to
      implement approach for future studies adding the GPAQ to the wearable of choice
      as a basis for comparisons.

PMID- 28520783
TI  - Effect of N-terminal region of nuclear Drosophila melanogaster small heat shock
      protein DmHsp27 on function and quaternary structure.
AB  - The importance of the N-terminal region (NTR) in the oligomerization and
      chaperone-like activity of the Drosophila melanogaster small nuclear heat shock
      protein DmHsp27 was investigated by mutagenesis using size exclusion
      chromatography and native gel electrophoresis. Mutation of two sites of
      phosphorylation in the N-terminal region, S58 and S75, did not affect the
      oligomerization equilibrium or the intracellular localization of DmHsp27 when
      transfected into mammalian cells. Deletion or mutation of specific residues
      within the NTR region delineated a motif (FGFG) important for the oligomeric
      structure and chaperone-like activity of this sHsp. While deletion of the full N
      terminal region, resulted in total loss of chaperone-like activity, removal of
      the (FGFG) at position 29 to 32 or single mutation of F29A/Y, G30R and G32R
      enhanced oligomerization and chaperoning capacity under non-heat shock conditions
      in the insulin assay suggesting the importance of this site for chaperone
      activity. Unlike mammalian sHsps DmHsp27 heat activation leads to enhanced
      association of oligomers to form large structures of approximately 1100 kDa. A
      new mechanism of thermal activation for DmHsp27 is presented.

PMID- 28520784
TI  - Presynaptic Abeta40 prevents synapse addition in the adult Drosophila
      neuromuscular junction.
AB  - Complexity in the processing of the Amyloid Precursor Protein, which generates a
      mixture of betaamyloid peptides, lies beneath the difficulty in understanding the
      etiology of Alzheimer's disease. Moreover, whether Abeta peptides have any
      physiological role in neurons is an unresolved question. By expressing single,
      defined Abeta peptides in Drosophila, specific effects can be discriminated in
      vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic
      expression of Abeta40 hinders the synaptic addition that normally occurs in
      adults, yielding NMJs with an invariable number of active zones at all ages
      tested. A similar trend is observed for Abeta42 at young ages, but net synaptic
      loss occurs at older ages in NMJs expressing this amyloid species. In contrast,
      Abeta42arc produces net synaptic loss at all ages tested, although age-dependent
      synaptic variations are maintained. Inhibition of the PI3K synaptogenic pathway
      may mediate some of these effects, because western analyses show that Abeta
      peptides block activation of this pathway, and Abeta species-specific
      synaptotoxic effects persists in NMJs overgrown by over-expression of PI3K.
      Finally, individual Abeta effects are also observed when toxicity is examined by
      quantifying neurodegeneration and survival. Our results suggest a physiological
      effect of Abeta40 in synaptic plasticity, and imply different toxic mechanisms
      for each peptide species.

PMID- 28520785
TI  - Prospective evidence for independent nitrogen and phosphorus limitation of
      grasshopper (Chorthippus curtipennis) growth in a tallgrass prairie.
AB  - Insect herbivores play a pivotal role in regulating plant production and
      community composition, and their role in terrestrial ecosystems is partly
      determined by their feeding behavior and performance among plants of differing
      nutritional quality. Historically, nitrogen (N) has been considered the primary
      limiting nutrient of herbivorous insects, but N is only one of many potential
      nutrients important to insect performance. Of these nutrients, phosphorus (P) is
      perhaps the most important because somatic growth depends upon P-rich ribosomal
      RNA. Yet relatively few studies have assessed the strength of P-limitation for
      terrestrial insects and even fewer have simultaneously manipulated both N and P
      to assess the relative strengths of N- and P-limitation. Here, we tested for
      potential N and P limitation, as well as N:P co-limitation, on Chorthippis
      curtipennis (Orthoptera, Acrididae), an abundant member of arthropod communities
      of central US prairies. Our results demonstrate weak evidence for both N and P
      limitation of C. curtipennis growth rates in laboratory feeding assays.
      Importantly, P-limitation was just as strong as N-limitation, but we found no
      evidence for NP co-limitation in our study. Furthermore, nutrient limitation was
      not apparent in field studies, suggesting that insect growth rates may be
      predominately controlled by other factors, including temperature and predation.
      Our results suggest that P should be jointly considered, along with N, as a
      primary determinant of herbivore feeding behavior under both current and future
      climate conditions.

PMID- 28520786
TI  - A systematic genetic screen for genes involved in sensing inorganic phosphate
      availability in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae responds to changes in extracellular inorganic phosphate
      (Pi) availability by regulating the activity of the phosphate-responsive (PHO)
      signaling pathway, enabling cells to maintain intracellular levels of the
      essential nutrient Pi. Pi-limitation induces upregulation of inositol
      heptakisphosphate (IP7) synthesized by the inositol hexakisphosphate kinase Vip1,
      triggering inhibition of the Pho80/Pho85 cyclin-cyclin dependent kinase (CDK)
      complex by the CDK inhibitor Pho81, which upregulates the PHO regulon through the
      CDK target and transcription factor Pho4. To identify genes that are involved in
      signaling upstream of the Pho80/Pho85/Pho81 complex and how they interact with
      each other to regulate the PHO pathway, we performed genome-wide screens with the
      synthetic genetic array method. We identified more than 300 mutants with defects
      in signaling upstream of the Pho80/Pho85/Pho81 complex, including AAH1, which
      encodes an adenine deaminase that negatively regulates the PHO pathway in a Vip1
      dependent manner. Furthermore, we showed that even in the absence of VIP1, the
      PHO pathway can be activated under prolonged periods of Pi starvation, suggesting
      complexity in the mechanisms by which the PHO pathway is regulated.

PMID- 28520788
TI  - Correction: Barriers to Timely and Safe Blood Transfusion for PPH Patients:
      Evidence from a Qualitative Study in Dhaka, Bangladesh.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0167399.].

PMID- 28520787
TI  - Development of an R4 dual-site (R4DS) gateway cloning system enabling the
      efficient simultaneous cloning of two desired sets of promoters and open reading
      frames in a binary vector for plant research.
AB  - Vast numbers of proteins work cooperatively to exert their functions in various
      cells. In order to understand the functions and molecular mechanisms of these
      proteins in plants, analyses of transgenic plants that concomitantly express two
      protein-coding genes are often required. We developed a novel Gateway cloning
      technology-compatible binary vector system, the R4 dual-site (R4DS) Gateway
      cloning system, which enables the easy and efficient cloning of two desired sets
      of promoters and open reading frames (ORFs) into a binary vector using promoter
      and ORF entry clones. In this system, C-terminal fusions with 17 kinds of tags
      including visible reporters and epitope tags are available for each ORF, and
      selection by four kinds of resistance markers is possible. We verified that the
      R4DS Gateway cloning system functioned well in Arabidopsis thaliana by observing
      the expression and localization patterns of fluorescent proteins fused with
      organelle-targeting signals and driven by stomatal-lineage specific promoters. We
      also confirmed that the two cloning sites in the R4DS Gateway cloning system were
      equivalent and independently regulated. The results obtained indicate that the
      R4DS Gateway cloning system facilitates detailed comparisons of the expression
      patterns of two promoters as well as co-localization and interaction analyses of
      two proteins in specific cells in plants.

PMID- 28520790
TI  - Correction: A Novel Quantitative Hemolytic Assay Coupled with Restriction
      Fragment Length Polymorphisms Analysis Enabled Early Diagnosis of Atypical
      Hemolytic Uremic Syndrome and Identified Unique Predisposing Mutations in Japan.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0124655.].

PMID- 28520789
TI  - Antigen-specific immunoglobulin variable region sequencing measures humoral
      immune response to vaccination in the equine neonate.
AB  - The value of prophylactic neonatal vaccination is challenged by the interference
      of passively transferred maternal antibodies and immune competence at birth.
      Taken our previous studies on equine B cell ontogeny, we hypothesized that the
      equine neonate generates a diverse immunoglobulin repertoire in response to
      vaccination, independently of circulating maternal antibodies. In this study,
      equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH)
      or equine influenza vaccine, and humoral immune responses were assessed using
      antigen-specific serum antibodies and B cell Ig variable region sequencing. An
      increase (p<0.0001) in serum KLH-specific IgG level was measured between days 21
      and days 28, 35 and 42 in vaccinated foals from non-vaccinated mares. In
      vaccinated foals from vaccinated mares, serum KLH-specific IgG levels tended to
      increase at day 42 (p = 0.07). In contrast, serum influenza-specific IgG levels
      rapidly decreased (p<=0.05) in vaccinated foals from vaccinated mares within the
      study period. Nevertheless, IGHM and IGHG sequences were detected in KLH- and
      influenza- sorted B cells of vaccinated foals, independently of maternal
      vaccination status. Immunoglobulin nucleotide germline identity, IGHV gene usage
      and CDR length of antigen-specific IGHG sequences in B cells of vaccinated foals
      revealed a diverse immunoglobulin repertoire with isotype switching that was
      comparable between groups and to vaccinated mares. The low expression of CD27
      memory marker in antigen-specific B cells, and of cytokines in peripheral blood
      mononuclear cells upon in vitro immunogen stimulation indicated limited
      lymphocyte population expansion in response to vaccine during the study period.

PMID- 28520791
TI  - Toxic and hormetic-like effects of three components of citrus essential oils on
      adult Mediterranean fruit flies (Ceratitis capitata).
AB  - Plant essential oils (EOs) and a wide range of their individual components are
      involved in a variety of biological interactions with insect pests including
      stimulatory, deterrent, toxic and even hormetic effects. Both the beneficial and
      toxic properties of citrus EOs on the Mediterranean fruit fly (medfly) have been
      experimentally evidenced over the last years. However, no information is
      available regarding the toxic or beneficial effects of the major components of
      citrus EOs via contact with the adults of the Mediterranean fruit fly. In the
      present study, we explored the toxicity of limonene, linalool and alpha-pinene (3
      of the main compounds of citrus EOs) against adult medflies and identified the
      effects of sub-lethal doses of limonene on fitness traits in a relaxed [full diet
      (yeast and sugar)] and in a stressful (sugar only) feeding environment. Our
      results demonstrate that all three compounds inferred high toxicity to adult
      medflies regardless of the diet, with males being more sensitive than females.
      Sub-lethal doses of limonene (LD20) enhanced the lifespan of adult medflies when
      they were deprived of protein. Fecundity was positively affected when females
      were exposed to limonene sub-lethal doses. Therefore, limonene, a major
      constituent of citrus EOs, induces high mortality at increased doses and positive
      effects on life history traits of medfly adults through contact at low sub-lethal
      doses. A hormetic-like effect of limonene to adult medflies and its possible
      underlying mechanisms are discussed.

PMID- 28520793
TI  - How does motion affect GABA-measurements? Order statistic filtering compared to
      conventional analysis of MEGA-PRESS MRS.
AB  - PURPOSE: The aim of this study was to evaluate two post-processing techniques
      applied to MRS MEGA-PRESS data influenced by motion-induced artifacts. In
      contrast to the conventional averaging technique, order statistic filtering (OSF)
      is a known method for artifact reduction. Therefore, this method may be suitable
      to incorporate in the GABA quantification. METHODS: Twelve healthy volunteers
      were scanned three times using a 3 T MR system. One measurement protocol
      consisted of two MEGA-PRESS measurements, one reference measurement and one
      measurement including head motions. The resulting datasets were analyzed with the
      standard averaging technique and with the OSF-technique in two schemes; filtering
      phase cycles 'RAW PC' and filtering dynamics 'RAW Dyn'. RESULTS: The datasets
      containing artifacts resulted in an underestimation of the concentrations. There
      was a trend for the OSF-technique to compensate for this reduction when
      quantifying SNR-intense signals. However, there was no indication that OSF
      improved the estimated GABA concentrations. Moreover, when only considering the
      reference measurements, the OSF technique was equally as effective as averaging,
      which suggests that the techniques are interchangeable. CONCLUSION: OSF performed
      equally well as the conventional averaging technique for low-SNR signals. For
      high-SNR signals, OSF performed better and thus could be considered for routine
      usage.

PMID- 28520794
TI  - The complex dynamics of products and its asymptotic properties.
AB  - We analyse global export data within the Economic Complexity framework. We couple
      the new economic dimension Complexity, which captures how sophisticated products
      are, with an index called logPRODY, a measure of the income of the respective
      exporters. Products' aggregate motion is treated as a 2-dimensional dynamical
      system in the Complexity-logPRODY plane. We find that this motion can be
      explained by a quantitative model involving the competition on the markets, that
      can be mapped as a scalar field on the Complexity-logPRODY plane and acts in a
      way akin to a potential. This explains the movement of products towards areas of
      the plane in which the competition is higher. We analyse market composition in
      more detail, finding that for most products it tends, over time, to a
      characteristic configuration, which depends on the Complexity of the products.
      This market configuration, which we called asymptotic, is characterized by higher
      levels of competition.

PMID- 28520792
TI  - MyD88 signaling in dendritic cells and the intestinal epithelium controls
      immunity against intestinal infection with C. rodentium.
AB  - MyD88-mediated signaling downstream of Toll-like receptors and the IL-1 receptor
      family is critically involved in the induction of protective host responses upon
      infections. Although it is known that MyD88-deficient mice are highly susceptible
      to a wide range of bacterial infections, the cell type-specific contribution of
      MyD88 in protecting the host against intestinal bacterial infection is only
      poorly understood. In order to investigate the importance of MyD88 in specific
      immune and nonimmune cell types during intestinal infection, we employed a novel
      murine knock-in model for MyD88 that enables the cell type-specific reactivation
      of functional MyD88 expression in otherwise MyD88-deficient mice. We report here
      that functional MyD88 signaling in CD11c+ cells was sufficient to activate
      intestinal dendritic cells (DC) and to induce the early group 3 innate lymphoid
      cell (ILC3) response as well as the development of colonic Th17/Th1 cells in
      response to infection with the intestinal pathogen C. rodentium. In contrast,
      restricting MyD88 signaling to several other cell types, including macrophages
      (MO), T cells or ILC3 did not induce efficient intestinal immune responses upon
      infection. However, we observed that the functional expression of MyD88 in
      intestinal epithelial cells (IEC) also partially protected the mice during
      intestinal infection, which was associated with enhanced epithelial barrier
      integrity and increased expression of the antimicrobial peptide RegIIIgamma and
      the acute phase protein SAA1 by epithelial cells. Together, our data suggest that
      MyD88 signaling in DC and IEC is both essential and sufficient to induce a full
      spectrum of host responses upon intestinal infection with C. rodentium.

PMID- 28520796
TI  - A hierarchical model for estimating the spatial distribution and abundance of
      animals detected by continuous-time recorders.
AB  - MOTIVATION: Several spatial capture-recapture (SCR) models have been developed to
      estimate animal abundance by analyzing the detections of individuals in a spatial
      array of traps. Most of these models do not use the actual dates and times of
      detection, even though this information is readily available when using
      continuous-time recorders, such as microphones or motion-activated cameras.
      Instead most SCR models either partition the period of trap operation into a set
      of subjectively chosen discrete intervals and ignore multiple detections of the
      same individual within each interval, or they simply use the frequency of
      detections during the period of trap operation and ignore the observed times of
      detection. Both practices make inefficient use of potentially important
      information in the data. MODEL AND DATA ANALYSIS: We developed a hierarchical SCR
      model to estimate the spatial distribution and abundance of animals detected with
      continuous-time recorders. Our model includes two kinds of point processes: a
      spatial process to specify the distribution of latent activity centers of
      individuals within the region of sampling and a temporal process to specify
      temporal patterns in the detections of individuals. We illustrated this SCR model
      by analyzing spatial and temporal patterns evident in the camera-trap detections
      of tigers living in and around the Nagarahole Tiger Reserve in India. We also
      conducted a simulation study to examine the performance of our model when
      analyzing data sets of greater complexity than the tiger data. BENEFITS: Our
      approach provides three important benefits: First, it exploits all of the
      information in SCR data obtained using continuous-time recorders. Second, it is
      sufficiently versatile to allow the effects of both space use and behavior of
      animals to be specified as functions of covariates that vary over space and time.
      Third, it allows both the spatial distribution and abundance of individuals to be
      estimated, effectively providing a species distribution model, even in cases
      where spatial covariates of abundance are unknown or unavailable. We illustrated
      these benefits in the analysis of our data, which allowed us to quantify
      differences between nocturnal and diurnal activities of tigers and to estimate
      their spatial distribution and abundance across the study area. Our continuous
      time SCR model allows an analyst to specify many of the ecological processes
      thought to be involved in the distribution, movement, and behavior of animals
      detected in a spatial trapping array of continuous-time recorders. We plan to
      extend this model to estimate the population dynamics of animals detected during
      multiple years of SCR surveys.

PMID- 28520795
TI  - BIRC6 mediates imatinib resistance independently of Mcl-1.
AB  - Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of
      apoptosis proteins (IAPs), a family of functionally and structurally related
      proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in
      several different human cancers, however mechanisms regulating BIRC6 have not
      been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant
      chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts
      of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib
      sensitive CML cells (MYL). Thus we investigated the role of BIRC6 in mediating
      imatinib resistance and compared it to the well-characterized anti-apoptotic
      protein, Mcl-1. Both BIRC6 and Mcl-1 were elevated in MYL-R compared to MYL
      cells. Lentiviral shRNA knockdown of BIRC6 in MYL-R cells increased imatinib
      stimulated caspase activation and resulted in a ~20-25-fold increase in imatinib
      sensitivity, without affecting Mcl-1. Treating MYL-R cells with CDK9 inhibitors
      decreased BIRC6 mRNA, but not BIRC6 protein levels. By contrast, while CDK9
      inhibitors reduced Mcl-1 mRNA and protein, they did not affect imatinib
      sensitivity. Since the Src family kinase Lyn is highly expressed and active in
      MYL-R cells, we tested the effects of Lyn inhibition on BIRC6 and Mcl-1. RNAi
      mediated knockdown or inhibition of Lyn (dasatinib/ponatinib) reduced BIRC6
      protein stability and increased caspase activation. Inhibition of Lyn also
      increased formation of an N-terminal BIRC6 fragment in parallel with reduced
      amount of the BIRC6 phosphopeptide, suggesting that Lyn may regulate BIRC6
      phosphorylation and stability. In summary, our data show that BIRC6 stability is
      dependent on Lyn, and that BIRC6 mediates imatinib sensitivity independently of
      Mcl-1 or CDK9. Hence, BIRC6 may be a novel target for the treatment of drug
      resistant CML where Mcl-1 or CDK9 inhibitors have failed.

PMID- 28520797
TI  - Cytogenetic studies on populations of Camponotus rufipes (Fabricius, 1775) and
      Camponotus renggeri Emery, 1894 (Formicidae: Formicinae).
AB  - Two valid ant species, Camponotus rufipes and Camponotus renggeri, have recently
      been the subject of a broad discussion with reference to taxa synonymization.
      Both species are quite common among the Neotropical myrmecofauna and share some
      unique traits, such as the shape of the scape and the pilosity patterns of the
      tibiae and scapes. A single morphological trait can help distinguish these
      species; however, only a combination of different approaches can enlighten our
      view of the complex phylogenetic relationships prevailing in the different
      populations of these two taxa. Therefore, focusing on the taxonomic issues
      concerning these two species, a cytogenetic survey including 10 populations of C.
      rufipes and two populations of C. renggeri was performed. In order to better
      understand the extent of the relationship between C. rufipes and C. renggeri, two
      common Neotropical Camponotus species, C. atriceps and C. cingulatus were taken
      as outgroups. All four species of Camponotus that were studied had 2n = 40
      chromosomes (4sm+34st+2t); however, the abundance of chromosome rearrangements
      observed, combined with several chromosome markers, suggest that C. rufipes and
      C. renggeri are two good distinct species although closely related. The already
      reported chromosome translocation 2n = 39 (1m+4sm+32st+2t) for C. rufipes has
      been found in different populations as in the unprecedented chromosome inversions
      found both in C. rufipes and in C. renggeri populations. Within the C. renggeri
      chromosome inversions, both the heterozygous state 2n = 40 (1m+3sm+34st+2t) and
      the homozygous state, 2n = 40 (2m+2sm+34st+2t) were identified. However, only
      heterozygous specimens for chromosome inversions were found among C. rufipes,
      with karyotype configurations distinct from those found in C. renggeri, with 2n =
      40 (1m+4sm+34st+2t). None of the populations studied showed signs of mosaic
      individuals. With respect to rDNA clusters, the 18S rDNA seemed to be more
      restricted inside the genome, as C. renggeri showed four 18S rDNA clusters,
      whereas, C. rufipes, C. atriceps, and C. cingulatus showed only two clusters. The
      chromosome locations of the 5S rDNA clusters were pointed for the first time in
      Formicidae, and showed itself to be more widely spread over the genome. By
      combining different chromosome banding approaches it was possible to demonstrate
      the crucial importance that chromosome inversions played on the karyotype
      evolution within these ants. The results also showed that chromosome
      translocations might be a consequence of the chromatin dynamic condition observed
      among Camponotus species. The homozygosis condition found in a C. renggeri from a
      Brazilian savanna population for chromosome inversions and the contrasting
      heterozygous condition for a different kind of chromosome inversion in C. rufipes
      from the Brazilian coastal rainforest, opens the window for a chromosome race
      hypothesis within the group C. renggeri and C. rufipes. The wide distribution,
      rich ecological interactions, genetic diversity, and morphological variability
      among C. renggeri and C. rufipes justify questioning of the actual taxonomic
      status of these species. The answer of this puzzle is clear when observing the
      number of 18S rDNA clusters of these ants, as C. rufipes has only two clusters
      whereas C. renggeri has four.

PMID- 28520798
TI  - Assessment of the accuracy of a new tool for the screening of smartphone
      addiction.
AB  - OBJECTIVE: To translate, adapt and validate the Smartphone Addiction Inventory
      (SPAI) in a Brazilian population of young adults. METHOD: We employed the
      translation and back-translation method for the adaptation of the Brazilian
      version SPAI (SPAI-BR). The sample consisted of 415 university students. Data was
      collected through an electronic questionnaire, which consisted of the SPAI-BR and
      the Goodman Criteria (gold standard). The retests were carried out 10-15 days
      after the initial tests with 130 individuals. RESULTS: The SPAI-BR maintained
      semantic, idiomatic and conceptual equivalences from the original scale. The
      Confirmatory Factor Analysis confirmed the One-factor model of the SPAI with good
      fit indexes (x2 = 767.861, CFI = 0.913, TLI = 0.905, RMSE = 0.061, WRMR = 1.465).
      The Kuder-Richardson Coefficient showed good internal consistency. The analysis
      of the ROC curve established an area under the curve of 86.38%. The Intraclass
      Correlation Coefficient of 0.926 between the test and the retest demonstrated an
      excellent temporal stability. The high correlation between SPAI-BR and the
      Goodman Criteria (rs = 0.750) established the convergent validity. CONCLUSION:
      The SPAI-BR is a valid and reliable tool for the detection of Smartphone
      Addiction in Brazilian university students.

PMID- 28520799
TI  - Nonenzymatic glycosylation of human serum albumin and its effect on antibodies
      profile in patients with diabetes mellitus.
AB  - BACKGROUND: Albumin glycation and subsequent formation of advanced glycation end
      products (AGEs) correlate with diabetes and associated complications. METHODS:
      Human Serum Albumin (HSA) was modified with D-glucose for a 40 day period under
      sterile conditions at 37 degrees C. Modified samples along with native HSA
      (unmodified) were analyzed for structural modifications by UV and fluorescence,
      FTIR, Liquid chromatography mass spectrometry (LCMS) and X-ray crystallography.
      New-Zealand white female rabbits immunized with AGEs, represent auto-antibodies
      formation as assessed by competitive and direct binding enzyme-linked
      immunosorbent assay (ELISA). Neo-epitopesagainst In-vitro formed AGEs were
      characterized in patients with diabetes mellitus type 2 (n = 50), type 1 (n =
      50), gestational diabetes (n = 50) and type 2 with chronic kidney disease (CKD)
      with eGFR level 60-89 mL/min (n = 50) from serum direct binding ELISA. RESULTS:
      Glycated-HSA showed amarked increase in hyperchromicity of 65.82%,71.98%, 73.62%
      and 76.63% at lambda280 nm along with anincreasein fluorescence intensity of
      65.82%, 71.98%, 73.62% and 76.63% in glycated-HSA compared to native. FTIR
      results showed theshifting of Amide I peak from 1656 cm_1 to 1659 cm_1 and Amide
      II peak from 1554 cm_1 to 1564 cm_1 in glycated-HSA, with anew peak appearance of
      carbonyl group at 1737 cm-1. LCMS chromatogram of glycated-HSA showed thepresence
      of carboxymethyl lysine (CML) at 279.1 m/z. Immunological analysis showed high
      antibody titre>1:12,800 in theserum of rabbits immunized with glycated-HSA
      (modified with 400 mg/dL glucose) and inhibition of 84.65% at anantigen
      concentration of 20MUg/mL. Maximum serum auto-antibody titre was found in T2DM
      (0.517+/-0.086), T1DM (0.108+/-0.092), GDM (0.611+/-0.041) and T2DM+CKD (0.096+/
      0.25) patients immunized with glycated-HSA (modified with 400 mg/dL glucose).
      CONCLUSIONS: Non-enzymatic glycosylation of HSA manifests immunological
      complications in diabetes mellitus due to change in its structure that enhances
      neo-epitopes generation.

PMID- 28520801
TI  - Group participants' experiences of a patient-directed group-based education
      program for the management of type 2 diabetes mellitus.
AB  - OBJECTIVE: The objective of this study was to explore the experiences of
      individuals who participated in a group-based education program, including their
      motivators in relation to their diabetes management, and the perceived impact of
      group interactions on participants' experiences and motivation for self
      management. Understanding individuals diagnosed with diabetes experiences of
      group-based education for the management of type 2 diabetes mellitus may guide
      the development and facilitation of these programs. METHODS: Semi-structured
      interviews were conducted with all individuals who participated in the
      intervention. Using thematic analysis underpinned by self-determination theory,
      we developed themes that explored participants' motivators in relation to
      diabetes management and the impact of group interactions on their experiences and
      motivation. RESULTS: The key themes included knowledge, experience, group
      interactions and motivation. Participants perceived that the group interactions
      facilitated further learning and increased motivation, achieved through
      normalization, peer identification or by talking with, and learning from the
      experience of others. CONCLUSIONS: The results support the use of patient-centred
      programs that prioritize group interactions over the didactic presentation of
      content, which may address relevant psychological needs of people diagnosed with
      type 2 diabetes mellitus, and improve their motivation and health behaviours.
      Future group-based education programs may benefit from the use of self
      determination theory as a framework for intervention design to enhance
      participant motivation.

PMID- 28520800
TI  - Transcriptome profiling revealed novel transcriptional regulators in maize
      responses to Ostrinia furnacalis and jasmonic acid.
AB  - Chewing insects cause severe yield losses in crop production worldwide. Crop
      plants counteract chewing insects by transcriptionally promoting a repertoire of
      defense gene products that are either toxic to, or attractive to the natural
      enemies of, pest insects. However, the complexity of the transcriptional
      reprogramming in plant defense response against chewing insects is still not well
      understood. In this study, the genome-wide early responses in maize seedlings to
      Asian corn borer (ACB, Ostrinia furnacalis) and also to jasmonic acid(JA), the
      pivotal phytohormone controlling plant defense response against herbivory, were
      transcriptionally profiled by RNA-Seq. Clustering of differentially expressed
      genes (DEGs) along with functional enrichment analysis revealed important
      biological processes regulated in response to ACB infestation and/or jasmonic
      acid. Moreover, DEGs with distinct expression patterns were differentially
      enriched with diverse families of cis-elements on their promoters. Multiple
      inventories of differentially expressed transcription factors (DETFs) in each DEG
      group were also analyzed. A transient expression assay using transfected maize
      protoplastswas established to examine the potential roles of DETFs in maize
      defense response and JA signaling, and this was used to show that ZmNAC60, an ACB
      and JA-inducible DETF, represented a novel positive regulator of JA and defense
      pathway genes. This study provided a comprehensive transcriptional picture for
      the early dynamics of maize defense responses and JA signaling, and the
      identification of DETFs offered potential targets for further functional genomics
      investigation of master regulators in maize defense responses against herbivory.

PMID- 28520802
TI  - Aquatic cycling-What do we know? A scoping review on head-out aquatic cycling.
AB  - Over the past few years, aquatic cycling has become a trending fitness activity.
      However, the literature has not been reviewed exhaustively. Therefore, using
      scoping review methodology, the aim of this review was to explore the current
      state of the literature concerning aquatic cycling. This study specifically
      focused on study designs, populations and outcomes. A comprehensive search of
      seven databases (PubMed, MEDLINE, Cinahl, Embase, PEDro,Web of Science, WorldCat)
      was conducted up to 30th September 2016. GoogleScholar, World Cat, ResearchGate,
      specific aquatic therapy websites and aquatic therapy journals were searched to
      identify additional literature. Full-text publications in English, German or
      Dutch were included. Studies were included when the intervention involved head
      out cycling carried out in 10 degrees  to 35 degrees  Celsius water. Exclusion
      criteria were the use of wet suits or confounding interventions that would affect
      participants' homeostasis. 63 articles were included and the study parameters of
      these studies were summarized. Using three grouping themes, included studies were
      categorised as 1) single session tests comparing aquatic versus land cycling, or
      2) aquatic cycling only sessions investigating different exercise conditions and
      3) aquatic cycling intervention programmes. Although the experimental conditions
      differed noticeably across the studies, shared characteristics were identified.
      Cardiovascular parameters were investigated by many of the studies with the
      results suggesting that the cardiac demand of aquatic cycling seems similar to
      land-based cycling. Only six studies evaluated the effect of aquatic cycling
      interventions. Therefore, future research should investigate the effects of
      aquatic cycling interventions, preferably in individuals that are expected to
      gain health benefits from aquatic cycling. Moreover, this comprehensive outline
      of available literature could serve as a starting point for systematic reviews or
      clinical studies on the effects of aquatic cycling on the cardiovascular
      responses.

PMID- 28520804
TI  - Inpatient Z-drug use commonly exceeds safe dosing recommendations.
AB  - IMPORTANCE: In 2016 recommendations for safer prescribing practices were
      circulated to all doctors in one of Canada's largest provinces, by the college of
      physicians, following a coroner's inquest into a vehicular death related to Z
      drug use. We sought to determine how frequently Z-drug prescriptions in our
      institution were not adhering to these recommendations. DESIGN: Retrospective
      cohort study. SETTING: McGill University Health Centre, an 832-bed tertiary care
      institution in Montreal, Canada. PARTICIPANTS: All adult non-obstetrical patients
      admitted between April 1, 2015 and March 31, 2016. EXPOSURE: The receipt of at
      least one dose of Z-drug as determined by pharmacy records. MAIN OUTCOMES AND
      MEASURES: Adherence to four recommendations related to starting dose, maximal
      dose, concomitant drug administration, and duration of use were evaluated.
      RESULTS: 1,409 unique patients received a Z-drug during 1,783 admissions
      representing use in 9.3% of non-obstetrical patients. Standing orders were seen
      in 42% (745/1783) of admissions. Non-conformity with the coroner's
      recommendations was common. Overall, 672/1783 (38%) admissions involved a patient
      receiving more than the recommended daily maximum dose (643/999 older patients,
      64%). Of 607 admissions which were longer than 10 days, 257 (39%) involved a
      prescription which exceeded 10 days. CONCLUSIONS AND RELEVANCE: A coroner's
      recommendation that doctors receive instructions about safe Z-drug prescribing is
      unprecedented, and was likely required given that use of Z-drugs occurs at doses
      and durations that often exceed best practice recommendations. Similar
      interventions may be required in other jurisdictions.

PMID- 28520803
TI  - Multiple modality biomarker prediction of cognitive impairment in prospectively
      followed de novo Parkinson disease.
AB  - OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline
      in Parkinson's disease (PD) to inform patient management, clinical trial design,
      and development of treatments. METHODS: We longitudinally assessed, up to 3
      years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline,
      from 33 international movement disorder centers. Study outcomes were four
      determinations of cognitive impairment or decline, and biomarker predictors were
      baseline dopamine transporter (DAT) single photon emission computed tomography
      (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness),
      diffusion tensor imaging (mean diffusivity and fractional anisotropy),
      cerebrospinal fluid (CSF; amyloid beta [Abeta], tau and alpha synuclein), and 11
      single nucleotide polymorphisms (SNPs) previously associated with PD cognition.
      Additionally, longitudinal structural MRI and DAT scan data were included.
      Univariate analyses were run initially, with false discovery rate = 0.2, to
      select biomarker variables for inclusion in multivariable longitudinal mixed
      effect models. RESULTS: By year 3, cognitive impairment was diagnosed in 15-38%
      participants depending on the criteria applied. Biomarkers, some longitudinal,
      predicting cognitive impairment in multivariable models were: (1) dopamine
      deficiency (decreased caudate and putamen DAT availability); (2) diffuse,
      cortical decreased brain volume or thickness (frontal, temporal, parietal, and
      occipital lobe regions); (3) co-morbid Alzheimer's disease Abeta amyloid
      pathology (lower CSF Abeta 1-42); and (4) genes (COMT val/val and BDNF val/val
      genotypes). CONCLUSIONS: Cognitive impairment in PD increases in frequency 50
      200% in the first several years of disease, and is independently predicted by
      biomarker changes related to nigrostriatal or cortical dopaminergic deficits,
      global atrophy due to possible widespread effects of neurodegenerative disease,
      co-morbid Alzheimer's disease plaque pathology, and genetic factors.

PMID- 28520805
TI  - Identification of key contributors in complex population structures.
AB  - Evaluating the genetic contribution of individuals to population structure is
      essential to select informative individuals for genome sequencing, genotype
      imputation and to ascertain complex population structures. Existing methods for
      the selection of informative individuals for genomic imputation solely focus on
      the identification of key ancestors, which can lead to a loss of phasing accuracy
      of the reference population. Currently many methods are independently applied to
      investigate complex population structures. Based on the Eigenvalue Decomposition
      (EVD) of a genomic relationship matrix we describe a novel approach to evaluate
      the genetic contribution of individuals to population structure. We combined the
      identification of key contributors with model-based clustering and population
      network visualization into an integrated three-step approach, which allows
      identification of high-resolution population structures and substructures around
      such key contributors. The approach was applied and validated in four disparate
      datasets including a simulated population (5,100 individuals and 10,000 SNPs), a
      highly structured experimental sheep population (1,421 individuals and 44,693
      SNPs) and two large complex pedigree populations namely horse (1,077 individuals
      and 38,124 SNPs) and cattle (2,457 individuals and 45,765 SNPs). In the simulated
      and experimental sheep dataset, our method, which is unsupervised, successfully
      identified all known key contributors. Applying our three-step approach to the
      horse and cattle populations, we observed high-resolution population
      substructures including the absence of obvious important key contributors.
      Furthermore, we show that compared to commonly applied strategies to select
      informative individuals for genotype imputation including the computation of
      marginal gene contributions (Pedig) and the optimization of genetic relatedness
      (Rel), the selection of key contributors provided the highest phasing accuracies
      within the selected reference populations. The presented approach opens new
      perspectives in the characterization and informed management of populations in
      general, and in areas such as conservation genetics and selective animal breeding
      in particular, where assessing the genetic contribution of influential and
      admixed individuals is crucial for research and management applications. As such,
      this method provides a valuable complement to common applied tools to visualize
      complex population structures and to select individuals for re-sequencing.

PMID- 28520807
TI  - Time from HIV diagnosis to commencement of antiretroviral therapy as an indicator
      to supplement the HIV cascade: Dramatic fall from 2011 to 2015.
AB  - INTRODUCTION: The HIV care cascade is increasingly used to evaluate HIV treatment
      programs at the population level. However, the cascade indicators lack the
      ability to show changes over time, which reduces their utility to guide health
      policy. Alternatives have been proposed but are complex or result in a delay in
      results. We propose a new indicator of ART uptake, the time from HIV diagnosis to
      commencement of ART, and compare it to the existing cascade indicator of
      proportion of patients on treatment and the WHO proposed cohort cascade indicator
      of proportion of patients on treatment within one year of diagnosis. METHODS AND
      MATERIALS: Records from patients from the two largest HIV treatment centres in
      the state of Victoria, Australia (Melbourne Sexual Health Centre and The Alfred
      Hospital Department of Infectious Diseases) from 2011 to 2015 were extracted. The
      intervals between date of diagnosis, entry into care and initiation of ART were
      compared. RESULTS AND DISCUSSION: From 2011 to 2015 the proportion of in-care
      patients who were on ART rose from 87% to 93% (p<0.0001). From 2011 to 2014, the
      proportion of patients in care and on ART within one year of diagnosis increased
      from 43.4% to 78.9% (p = 0.001). The median time from diagnosis to ART fell from
      418 days (IQR: 91-1176) to 77 days (IQR: 39-290)(p<0.001) by calendar year in
      which ART was commenced. CONCLUSIONS: From 2011 to 2015 there were substantial
      and clinically important falls in the median time from diagnosis to commencing
      ART in those that commenced ART. The size of this dramatic change was not
      apparent when only reporting the proportion of patients on ART. Time to ART is a
      useful indicator and can be used to supplement existing cascade indicators in
      measuring progress toward universal ART coverage.

PMID- 28520806
TI  - ALS skeletal muscle shows enhanced TGF-beta signaling, fibrosis and induction of
      fibro/adipogenic progenitor markers.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which
      upper and lower motoneurons degenerate leading to muscle wasting, paralysis and
      eventually death from respiratory failure. Several studies indicate that skeletal
      muscle contributes to disease progression; however the molecular mechanisms
      remain elusive. Fibrosis is a common feature in skeletal muscle under chronic
      damage conditions such as those caused by muscular dystrophies or denervation.
      However, the exact mechanisms of fibrosis induction and the cellular bases of
      this pathological response are unknown. We show that extracellular matrix (ECM)
      components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a
      widely used murine model of ALS. These mice also show increased TGF-beta1 mRNA
      levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore,
      platelet-derived growth factor receptor-alpha (PDGFRalpha), Tcf4 and alpha-smooth
      muscle actin (alpha-SMA) levels are augmented in the skeletal muscle of
      symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors
      (FAPs), which are the main producers of ECM constituents, are also increased in
      these pathogenic conditions. Therefore, FAPs and ECM components are more abundant
      in symptomatic stages of the disease than in pre-symptomatic stages. We present
      evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice
      is accompanied with an induction of TGF-beta signaling, and also that FAPs might
      be involved in triggering a fibrotic response. Co-localization of p-Smad3
      positive cells together with PDGFRalpha was observed in the interstitial cells of
      skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro
      fibrotic factors such as TGF-beta, CTGF/CCN2 and platelet-derived growth factor
      (PDGF) signaling pathway might be a suitable therapeutic approach to improve
      muscle function in several degenerative diseases.

PMID- 28520809
TI  - Antenatal coffee and tea consumption and the effect on birth outcome and
      hypertensive pregnancy disorders.
AB  - BACKGROUND AND OBJECTIVE: Coffee and tea are commonly consumed during pregnancy.
      While several of their components, like caffeine, have strong pharmacological
      effects, the effect on the unborn fetus remains unclear. Caffeine intake has been
      associated with abortion, preterm birth and fetal growth restriction, but a
      general consensus on caffeine restriction is still lacking. We aimed to
      investigate antenatal coffee, tea and caffeine consumption and the effect on
      birth weight and length, gestational age at birth and hypertensive disorders in
      pregnancy. METHODS: A total of 936 healthy pregnancies from the WHISTLER birth
      cohort with data on coffee and tea consumption were included. Maternal and child
      characteristics as well as antenatal coffee and tea consumption were obtained
      through postpartum questionnaires. Reported consumption was validated using
      available preconceptional data. Caffeine intake was calculated from coffee and
      tea consumption. Linear and logistic regression was used to assess the
      association with birth outcome and hypertensive disorders. RESULTS: After
      adjustment for smoking and maternal age, a daily consumption of more than 300mg
      of caffeine compared to less than 100mg of caffeine was significantly associated
      with an increased gestational age (linear regression coefficient = 2.00 days,
      95%CI = 0.12-4.21, P = 0.03). Tea consumption was significantly related to a
      higher risk of pregnancy induced hypertension (OR = 1.13, 95%CI = 1.04-1.23, P =
      0.004). No associations concerning coffee consumption or birth weight and birth
      length were observed. CONCLUSIONS: Daily caffeine consumption of more than 300mg
      is possibly associated with an increase in gestational age at birth. A possible
      relation between high tea consumption and increased risk for pregnancy induced
      hypertension warrants further research. For most outcomes, we found no
      significant associations with coffee or tea intake.

PMID- 28520808
TI  - Proteomic analysis of Biomphalaria glabrata plasma proteins with binding affinity
      to those expressed by early developing larval Schistosoma mansoni.
AB  - Interactions between early developing Schistosoma mansoni larval stages and the
      hemolymph of its snail intermediate host represent the first molecular encounter
      with the snail's immune system. To gain a more comprehensive understanding of
      this early parasite-host interaction, biotinylated sporocyst tegumental membrane
      (Mem) proteins and larval transformation proteins (LTP) were affixed to
      streptavidin-agarose beads and used as affinity matrices to enrich for larval
      reactive plasma proteins from susceptible (NMRI) and resistant (BS-90) strains of
      the snail Biomphalaria glabrata. Nano-LC/MS-MS proteomic analyses of isolated
      plasma proteins revealed a diverse array of 94 immune-and nonimmune-related
      plasma proteins. Included among the immune-related subset were pattern
      recognition receptors (lectins, LPS-binding protein, thioester-containing
      proteins-TEPs), stress proteins (HSP60 and 70), adhesion proteins
      (dermatopontins), metalloproteases (A Disintegrin And Metalloproteinase (ADAM),
      ADAM-related Zn proteinases), cytotoxins (biomphalysin) and a Ca2+-binding
      protein (neo-calmodulin). Variable immunoglobulin and lectin domain (VIgL) gene
      family members, including fibrinogen-related proteins (FREPs), galectin-related
      proteins (GREPs) and C-type lectin-related proteins (CREPs), were the most
      prevalent of larval-reactive immune lectins present in plasma. FREPs were highly
      represented, although only a subset of FREP subfamilies (FREP 2, 3 and 12) were
      identified, suggesting potential selectivity in the repertoire of plasma lectins
      recognizing larval glycoconjugates. Other larval-binding FREP-like and CREP-like
      proteins possessing a C-terminal fibrinogen-related domain (FReD) or C-type
      lectin binding domain, respectively, and an Ig-fold domain also were identified
      as predicted proteins from the B. glabrata genome, although incomplete sequence
      data precluded their placement into specific FREP/CREP subfamilies. Similarly, a
      group of FReD-containing proteins (angiopoeitin-4, ficolin-2) that lacked N
      terminal Ig-fold(s) were identified as a distinct group of FREP-like proteins,
      separate from the VIgL lectin family. Finally, differential appearance of GREPs
      in BS-90 plasma eluates, and others proteins exclusively found in eluates of the
      NMRI strain, suggested snail strain differences in the expression of select
      larval-reactive immune proteins. This hypothesis was supported by the finding
      that differential gene expression of the GREP in BS-90 and ADAM in NMRI snail
      strains generally correlated with their patterns of protein expression. In
      summary, this study is the first to provide a global comparative proteomic
      analysis of constitutively expressed plasma proteins from susceptible and
      resistant B. glabrata strains capable of binding early-expressed larval S.
      mansoni proteins. Identified proteins, especially those exhibiting differential
      expression, may play a role in determining immune compatibility in this snail
      host-parasite system. A complete listing of raw peptide data are available via
      ProteomeXchange using identifier PXD004942.

PMID- 28520810
TI  - Long chain saturated and unsaturated fatty acids exert opposing effects on
      viability and function of GLP-1-producing cells: Mechanisms of lipotoxicity.
AB  - BACKGROUND AND AIM: Fatty acids acutely stimulate GLP-1 secretion from L-cells in
      vivo. However, a high fat diet has been shown to reduce the density of L-cells in
      the mouse intestine and a positive correlation has been indicated between L-cell
      number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1
      secretion, potential effects of long-term exposure to elevated levels of
      different fatty acid species, and underlying mechanisms are not fully understood.
      In the present study, we sought to determine how long-term exposure to saturated
      (16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing
      cells, alter function and viability, and the underlying mechanisms. METHODS: GLP
      1-secreting GLUTag cells were cultured in the presence/absence of saturated
      (16:0) and unsaturated (18:1) fatty acids (0.125 mM for 48 h, followed by
      analyses of viability and apoptosis, as well as involvement of fatty acid
      oxidation, free fatty acid receptors (FFAR1) and ceramide synthesis. In addition,
      effects on the expression of proglucagon, prohormone convertase 1/3 (PC1/3), free
      fatty acid receptors (FFAR1, FFAR3), sodium glucose co-transporter (SGLT) and
      subsequent secretory response were determined. RESULTS: Saturated (16:0) and
      unsaturated (18:1) fatty acids exerted opposing effects on the induction of
      apoptosis (1.4-fold increase in DNA fragmentation by palmitate and a 0.5-fold
      reduction by oleate; p<0.01). Palmitate-induced apoptosis was associated with
      increased ceramide content and co-incubation with Fumonisin B1 abolished this
      lipo apoptosis. Oleate, on the other hand, reduced ceramide content, and-unlike
      palmitate-upregulated FFAR1 and FFAR3, evoking a 2-fold increase in FFAR1
      mediated GLP-1 secretion following acute exposure to 0.125 mmol/L palmitate;
      (p<0.05). CONCLUSION/INTERPRETATION: Saturated (16:0), but not unsaturated
      (18:1), fatty acids induce ceramide-mediated apoptosis of GLP-1-producing cells.
      Further, unsaturated fatty acids confer lipoprotection, enhancing viability and
      function of GLP-1-secreting cells. These data provide potential mechanistic
      insight contributing to reduced L-cell mass following a high fat diet and
      differential effects of saturated and unsaturated fatty acids on GLP-1 secretion
      in vivo.

PMID- 28520812
TI  - The effect of platelet-rich plasma on osseous healing in dogs undergoing high
      tibial osteotomy.
AB  - OBJECTIVES: The purpose of this study was to investigate whether platelet-rich
      plasma (PRP) enhances osseous healing in conjunction with a high tibial osteotomy
      in dogs. STUDY DESIGN: Randomized controlled trial. METHODS: Sixty-four client
      owned pet dogs with naturally occurring rupture of the anterior cruciate ligament
      and that were to be treated with a high tibial osteotomy (tibial plateau leveling
      osteotomy) were randomized into the treatment or control group. Dogs in the
      treatment group received autologous platelet-rich plasma activated with calcium
      chloride and bovine thrombin to produce a well-formed PRP gel that was placed
      into the osteotomy at the time of surgery. Dogs in the control group received
      saline lavage of the osteotomy. All dogs had the osteotomy stabilized with
      identical titanium alloy implants and all aspects of the surgical procedure and
      post-operative care were identical among dogs of the two groups. Bone healing was
      assessed at exactly 28, 49, and 70 days after surgery with radiography and
      ultrasonography and with MRI at day 28. The effect of PRP on bone healing was
      assessed using a repeated measures analysis of covariance with radiographic and
      ultrasonographic data and using a t-test with the MRI data. RESULTS: Sixty dogs
      completed the study. There were no significant differences in age, weight, or
      gender distribution between the treatment and control groups. Twenty-seven dogs
      were treated with PRP and 33 were in the control group. The average platelet
      concentration of the PRP was 1.37x106 platelets/MUL (+/-489x103) with a leukocyte
      concentration of 5.45x103/MUL (+/-3.5x103). All dogs demonstrated progressive
      healing over time and achieved clinically successful outcomes. Time since surgery
      and patient age were significant predictors of radiographic healing and time
      since surgery was a significant predictor of ultrasonographic assessment of
      healing. There was no significant effect of PRP treatment as assessed
      radiographically, ultrasonographically, or with MRI. CONCLUSION: The PRP used in
      this study did not hasten osseous union in dogs treated with a high tibial
      osteotomy.

PMID- 28520811
TI  - Body shape index: Sex-specific differences in predictive power for all-cause
      mortality in the Japanese population.
AB  - BACKGROUND: While body mass index (BMI) is the most widely used anthropometric
      measure, its association with all-cause mortality is generally J-shaped or U
      shaped. A body shape index (ABSI) is a recently formulated anthropometric measure
      that shows linear relationship to all-cause mortality, especially in Caucasian
      cohorts. We aimed to address the relationship between ABSI and all-cause
      mortality in Asians and to assess the influence of sex difference and of chronic
      kidney disease (CKD) on this relationship. METHODS: This was a longitudinal
      cohort study assessing the association of ABSI, BMI, waist circumference (WC),
      and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese
      nationwide Specific Health Checkup database. The study enrolled 160,625
      participants followed-up between 2008 and 2012. We calculated the all-cause
      mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI,
      BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. RESULTS:
      During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD)
      significantly increased the risk for all-cause mortality after adjusting for
      other known risk factors including CKD; hazard ratio (HR) and 95% confidence
      intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of
      CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show
      significant association with all-cause mortality, especially in the CKD cohort;
      HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of
      CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated
      with significantly lower risk in men, although minimal association was found in
      women. WC and WHtR showed little association with all-cause mortality. On
      stratification per ABSI quartiles, mortality risk increased linearly and
      significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed
      significant but U-shaped association with mortality in the non-CKD cohort and in
      men with CKD. WHtR also showed significant U-shaped association with mortality in
      men. CONCLUSIONS: In the Japanese population, ABSI showed significant and linear
      correlation with mortality risk in men but not in women, especially in the
      presence of CKD.

PMID- 28520813
TI  - Pancreatic fat content by magnetic resonance imaging in subjects with
      prediabetes, diabetes, and controls from a general population without
      cardiovascular disease.
AB  - BACKGROUND/OBJECTIVE: Despite the relevance of pancreatic fat content in the
      development of metabolic diseases, its association with impaired glucose
      metabolism, diabetes, and other adipose tissue compartments remains unclear.
      Thus, we determined differences in pancreatic fat content by magnetic resonance
      imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in
      a cohort from the general population. METHODS: Subjects without history of
      cardiovascular disease with established diabetes or prediabetes as well as normal
      controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic
      fat content was quantified by measuring the proton-density fat fraction
      (PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by
      placing ROIs in the pancreatic head, body, and tail by independent readers. In
      addition, hepatic fat content as well as abdominal subcutaneous and visceral
      adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point
      volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses
      were employed to determine associations. RESULTS: A total of 385 subjects were
      included in the analysis (median age: 57 years, 58.2% males), of them 53 were
      classified as subjects with diabetes, 95 as prediabetes, and 237 as controls
      (13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3
      9.4], and significantly higher in subjects with prediabetes and diabetes as
      compared to controls (PDFFpanc: 6.2% [IQR: 3.5-12] vs. 8.6% [IQR: 4.3-17.5] vs.
      4.9% [3.1-7.4], p<0.001, respectively). After adjusting for age, gender and BMI
      the association was attenuated (all p>0.12). While in univariate analysis BMI,
      PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p<0.05), only VAT
      predicted PDFFpanc independently (beta: 0.02, 95%-confidence interval: 0.01-0.04,
      p<0.001). CONCLUSION: While pancreatic fat content differs significantly between
      subjects with prediabetes, diabetes and controls, this association may be
      confounded by age, gender, and the amount of VAT in this cross-sectional study.

PMID- 28520814
TI  - Rs12970134 near MC4R is associated with appetite and beverage intake in
      overweight and obese children: A family-based association study in Chinese
      population.
AB  - BACKGROUND: Recent studies indicated that eating behaviors are under genetic
      influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect
      the total energy intake and the consumption of fat, protein and carbohydrates.
      Our study aims at investigating the association of the MC4R polymorphism with
      appetite and food intake among Chinese children. METHODS: A family-based
      association study was conducted among 151 Chinese trios whose offsprings were
      overweight/obese children aged 9-15 years. The rs12970134 near MC4R was
      genotyped, and the Children Eating Behavior Questionnaire (CEBQ) and a self
      designed questionnaire measuring food intake were performed. The FBAT and PBAT
      software packages were used. RESULTS: The family-based association analysis
      showed that there was a significant association between rs12970134 and obesity (Z
      = 2.449, P = 0.014). After adjusting for age, gender and standardized BMI,
      rs12970134 was significantly associated with food responsiveness (FR) among
      children (beta'b = 0.077, Pb = 0.028), and with satiety responsiveness (SR) in
      trios (P = -0.026). The polymorphism was associated with beverage intake (beta'b
      = 0.331, Pb = 0.00016 in children; P = 0.043 in trios), but not significantly
      associated with vegetable, fruit or meat intake (P>0.050). We further found a
      significant mediation effect among the rs12970134, FR and beverage intake (b =
      0.177, P = 0.047). CONCLUSIONS: Our study is the first to report that rs12970134
      near MC4R was associated with appetite and beverage intake, and food
      responsiveness could mediate the effect of rs12970134 on beverage intake in
      overweight and obese Chinese children population. Further studies are needed to
      uncover the genetic basis for eating behaviors, which could lead to develop and
      implement effective interventional strategies early in life.

PMID- 28520815
TI  - Metabolic profiling by gas chromatography-mass spectrometry of energy metabolism
      in high-fat diet-fed obese mice.
AB  - A novel, selective and sensitive single-ion monitoring (SIM) gas chromatography
      mass spectrometry (GCMS) method was developed and validated for the determination
      of energy metabolites related to glycolysis, the tricarboxylic acid (TCA) cycle,
      glutaminolysis, and fatty acid beta-oxidation. This assay used N-tert
      butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) containing 1% tert
      butyldimethylchlorosilane (TBDMCS) as derivatizing reagent and was highly
      reproducible, sensitive, specific and robust. The assay was used to analyze liver
      tissue and serum from C57BL/6N obese mice fed a high-fat diet (HFD) and C57BL/6N
      mice fed normal chow for 8 weeks. HFD-fed mice serum displayed statistically
      significantly reduced concentrations of pyruvate, citrate, succinate, fumarate,
      and 2-oxoglutarate, with an elevated concentration of pantothenic acid. In liver
      tissue, HFD-fed mice exhibited depressed levels of glycolysis end-products
      pyruvate and lactate, glutamate, and the TCA cycle intermediates citrate,
      succinate, fumarate, malate, and oxaloacetate. Pantothenate levels were 3-fold
      elevated accompanied by a modest increased gene expression of Scl5a6 that encodes
      the pantothenate transporter SLC5A6. Since both glucose and fatty acids inhibit
      coenzyme A synthesis from pantothenate, it was concluded that these data were
      consistent with downregulated fatty acid beta-oxidation, glutaminolysis,
      glycolysis, and TCA cycle activity, due to impaired anaplerosis. The novel SIM
      GCMS assay provided new insights into metabolic effects of HFD in mice.

PMID- 28520817
TI  - Heat in the southeastern United States: Characteristics, trends, and potential
      health impact.
AB  - High summer temperatures in extratropical areas have an impact on the public's
      health, mainly through heat stress, high air pollution concentrations, and the
      transmission of tropical diseases. The purpose of this study is to examine the
      current characteristics of heat events and future projections of summer apparent
      temperature (AT)-and associated health concerns-throughout the southeastern
      United States. Synoptic climatology was used to assess the atmospheric
      characteristics of extreme heat days (EHDs) from 1979-2015. Ozone concentrations
      also were examined during EHDs. Trends in summer-season AT over the 37-year
      period and correlations between AT and atmospheric circulation were determined.
      Mid-century estimates of summer AT were calculated using downscaled data from an
      ensemble of global climate models. EHDs throughout the Southeast were
      characterized by ridging and anticyclones over the Southeast and the presence of
      moist tropical air masses. Exceedingly high ozone concentrations occurred on EHDs
      in the Atlanta area and throughout central North Carolina. While summer ATs did
      not increase significantly from 1979-2015, summer ATs are projected to increase
      substantially by mid-century, with most the Southeast having ATs similar to that
      of present-day southern Florida (i.e., a tropical climate). High ozone
      concentrations should continue to occur during future heat events. Large urban
      areas are expected to be the most affected by the future warming, resulting from
      intensifying and expanding urban heat islands, a large increase in heat
      vulnerable populations, and climate conditions that will be highly suitable for
      tropical-disease transmission by the Aedes aegypti mosquito. This nexus of
      vulnerability creates the potential for heat-related morbidity and mortality, as
      well as the appearance of disease not previously seen in the region. These
      effects can be attenuated by policies that reduce urban heat (e.g., cool roofs
      and green roofs) and that improve infrastructure (e.g. emergency services,
      conditioned space).

PMID- 28520816
TI  - High prevalence of elevated blood lead levels in both rural and urban Iowa
      newborns: Spatial patterns and area-level covariates.
AB  - Lead in maternal blood can cross the placenta and result in elevated blood lead
      levels in newborns, potentially producing negative effects on neurocognitive
      function, particularly if combined with childhood lead exposure. Little research
      exists, however, into the burden of elevated blood lead levels in newborns, or
      the places and populations in which elevated lead levels are observed in
      newborns, particularly in rural settings. Using ~2300 dried bloods spots
      collected within 1-3 days of birth among Iowa newborns, linked with the area of
      mother's residence at the time of birth, we examine the spatial patterns of
      elevated (>5 MUg/dL) blood lead levels and the ecological-level predictors of
      elevated blood lead levels. We find that one in five newborns exceed the 5 MUg/dL
      action level set by the US Centers for Disease Control & Prevention (CDC).
      Bayesian spatial zero inflated regression indicates that elevated blood lead in
      newborns is associated with areas of increased pre-1940s housing and childbearing
      age women with low educational status in both rural and urban settings. No
      differences in blood lead levels or the proportion of children exceeding 5 MUg/dL
      are observed between urban and rural maternal residence, though a spatial cluster
      of elevated blood lead is observed in rural counties. These characteristics can
      guide the recommendation for testing of infants at well-baby appointments in
      places where risk factors are present, potentially leading to earlier initiation
      of case management. The findings also suggest that rural populations are at as
      great of risk of elevated blood lead levels as are urban populations. Analysis of
      newborn dried blood spots is an important tool for lead poisoning surveillance in
      newborns and can direct public health efforts towards specific places and
      populations where lead testing and case management will have the greatest impact.

PMID- 28520818
TI  - Evaluation of a real-time method of simultaneous amplification and testing in
      diagnosis of Mycoplasma pneumoniae infection in children with pneumonia.
AB  - Mycoplasma pneumoniae (M. pneumoniae) infection can cause community acquired
      pneumonia in children. A real-time method of simultaneous amplification and
      testing of M. pneumoniae (SAT-MP) was developed to diagnose M. pneumoniae
      targeting a region of the ribosomal RNA. The SAT-MP assay can accurately identify
      M. pneumoniae with a detection range from 101 to 107 CFU/ml. In this study, the
      specimens from 315 children with pneumonia were collected and analyzed by SAT-MP
      in parallel with real-time PCR method and IgM ELISA assay. The positive rates of
      these specimens examined by SAT-MP assay, real-time PCR method and IgM ELISA
      assay were 16.51%, 15.56% and 12.70% respectively. While there was statistical
      significance (p = 0.04) between SAT-MP assay and IgM ELISA assay, no statistical
      significance (p = 0.25) was found between SAT-MP assay and real-time PCR method
      and these two methods had high consistency (kappa value = 0.97). These findings
      indicate that the newly developed SAT-MP assay is a rapid, sensitive and specific
      method for identifying M. pneumoniae with potential clinical application in the
      early diagnosis of M. pneumoniae infection.

PMID- 28520820
TI  - Association between features of patient-provider discussions and routine prostate
      specific antigen testing.
AB  - INTRODUCTION: Although the US Preventive Services Task Force recommends against
      routine prostate cancer screening with prostate-specific antigen (PSA) testing,
      specialty organizations support screening via shared decision making between
      providers and selected patients. While discussions about advantages and
      disadvantages of testing are a feature of patient-centered care, it is unclear
      how provider recommendations and the presence of a personal doctor influence
      testing in the presence of such discussions. MATERIALS AND METHODS: We used the
      2013 Behavioral Risk Factor Surveillance System to identify 1,737 male
      respondents surveyed about their PSA testing decisions. We describe the
      prevalence of provider recommendations and utilize weighted multivariable
      logistic regression models to examine the impact of provider recommendations and
      presence of a personal doctor on routine testing while accounting for patient
      provider discussions about advantages and disadvantages. RESULTS: The majority
      (70.4%) of respondents reported some form of discussion with providers about
      testing and most underwent screening in accordance with provider recommendations.
      In multivariable analyses, men whose providers had never recommended PSA test
      were less likely to receive screening [OR 0.03, 95% CI (0.02-0.05)], and patients
      who did not identify a personal doctor in their care were less likely to undergo
      testing [OR 0.12, 95% CI (0.04-0.32)]. DISCUSSION: Provider recommendations and
      having a personal doctor are associated with routine PSA testing. These findings
      suggest that providers and policymakers should be aware of how the content and
      context of communication with patients, beyond discussions of risks and benefits,
      can influence routine PSA testing behaviors.

PMID- 28520819
TI  - In vitro analysis of the segmental flexibility of the thoracic spine.
AB  - Basic knowledge about the thoracic spinal flexibility is limited and to the
      authors' knowledge, no in vitro studies have examined the flexibility of every
      thoracic spinal segment under standardized experimental conditions using pure
      moments. In our in vitro study, 68 human thoracic functional spinal units
      including the costovertebral joints (at least n = 6 functional spinal units per
      segment from T1-T2 to T11-T12) were loaded with pure moments of +/-7.5 Nm in
      flexion/extension, lateral bending, and axial rotation in a custom-built spine
      tester to analyze range of motion (ROM) and neutral zone (NZ). ROM and NZ showed
      symmetric motion behavior in all loading planes. In each loading direction, the
      segment T1-T2 exhibited the highest ROM. In flexion/extension, the whole thoracic
      region, with exception of T1-T2 (14 degrees ), had an average ROM between 6
      degrees  and 8 degrees . In lateral bending, the upper thoracic region (T1-T7)
      was, with an average ROM between 10 degrees  and 12 degrees , more flexible than
      the lower thoracic region (T7-T12) with an average ROM between 8 degrees  and 9
      degrees . In axial rotation, the thoracic region offered the highest overall
      flexibility with an average ROM between 10 degrees  and 12 degrees  in the upper
      and middle thoracic spine (T1-T10) and between 7 degrees  and 8 degrees  in the
      lower thoracic spine (T10-T12), while a trend of continuous decrease of ROM could
      be observed in the lower thoracic region (T7-T12). Comparing these ROM values
      with those in literature, they agree that ROM is lowest in flexion/extension and
      highest in axial rotation, as well as decreasing in the lower segments in axial
      rotation. Differences were found in flexion/extension and lateral bending in the
      lower segments, where, in contrast to the literature, no increase of the ROM from
      superior to inferior segments was found. The data of this in vitro study could be
      used for the validation of numerical models and the design of further in vitro
      studies of the thoracic spine without the rib cage, the verification of animal
      models, as well as the interpretation of already published human in vitro data.

PMID- 28520822
TI  - Correction: Biochemical evaluation of the anticancer potential of the polyamine
      based nanocarrier Nano11047.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0175917.].

PMID- 28520824
TI  - Expanding Purpura in a Neutropenic Patient.

PMID- 28520821
TI  - The percentage of Epidermal Growth Factor Receptor (EGFR)-mutated neoplastic
      cells correlates to response to tyrosine kinase inhibitors in lung
      adenocarcinoma.
AB  - BACKGROUND: Epidermal Growth Factor Receptor (EGFR) molecular analysis is
      performed to assess the responsiveness to Tyrosine Kinase Inhibitors (TKIs) in
      patients with Non-Small Cell Lung Cancer (NSCLC). The existence of molecular
      intra-tumoral heterogeneity has been observed in lung cancers. The aim of the
      present study is to investigate if the percentage of mutated neoplastic cells
      within the tumor sample might influence the responsiveness to TKIs treatment.
      MATERIAL AND METHODS: A total of 931 cases of NSCLC were analyzed for EGFR
      mutational status (exon 18, 19, 20, 21) using Next Generation Sequencer. The
      percentage of mutated neoplastic cells was calculated after normalizing the
      percentage of mutated alleles obtained after next generation sequencer analysis
      with the percentage of neoplastic cells in each tumor. RESULTS: Next generation
      sequencing revealed an EGFR mutation in 167 samples (17.9%), mainly deletions in
      exon 19. In 18 patients treated with TKIs and with available follow-up, there was
      a significant correlation between the percentage of mutated neoplastic cells and
      the clinical response (P = 0.017). Patients with a percentage of mutated
      neoplastic cells greater than 56%, have a statistical trend (P = 0.081) for
      higher Overall Survival (26.3 months) when compared to those with a rate of
      mutated neoplastic cells lower than 56% (8.2 months). CONCLUSIONS: The percentage
      of EGFR-mutated neoplastic cells in the tumor is associated with response to
      TKIs. A "quantitative result" of EGFR mutational status might provide useful
      information in order to recognize those patients which might have the greatest
      benefit from TKIs.

PMID- 28520825
TI  - Toward Palliative Care for All Patients With Advanced Cancer.

PMID- 28520823
TI  - Comparison of Tunnel and Crestal Incision Techniques in Reconstruction of
      Localized Alveolar Defects.
AB  - PURPOSE: The aim of this study was to compare the complication rates of recipient
      sites prepared using two incision techniques: crestal and tunnel. MATERIALS AND
      METHODS: In this prospective study, patients underwent augmentation procedures
      (68 patients; 75 sites) by the same surgeon that were performed consecutively
      using the crestal incision technique (27 horizontal, 10 vertical; crestal group)
      or the tunnel incision technique (27 horizontal, 11 vertical; tunnel group).
      Autogenous bone block grafts were harvested with a piezoelectric surgical device,
      and the grafts were fixed at the recipient sites by two titanium screws in both
      groups. The authors evaluated minor exposure, transient paresthesia, major
      exposure, permanent paresthesia, gingival recession at adjacent teeth, surgery
      time, and visual analog scale pain scores. RESULTS: Soft tissue dehiscence and
      graft failure were significantly lower in patients undergoing the tunnel
      technique. CONCLUSION: The tunnel incision technique significantly decreased soft
      tissue exposure, the most common complication of augmentation procedures with
      autogenous onlay bone grafts. This technique should be considered an alternative
      to the crestal incision technique for preparation of the recipient site.

PMID- 28520826
TI  - Current Challenges Associated With Next-Generation Sequencing of Breast Cancer
      Reply.

PMID- 28520827
TI  - Surgical Outcomes of Bony Batten Grafting to Correct Caudal Septal Deviation in
      Septoplasty.
AB  - Improtance: Correction of caudal septal deviation with a batten graft has been
      popularized recently. However, few reports have documented the surgical outcomes
      of this technique, especially the use of bony batten grafts in septoplasty.
      Objective: To evaluate the surgical outcomes of bony batten grafting for the
      management of caudal septal deviation in endonasal septoplasty. Design, Setting,
      and Participants: This retrospective cohort study evaluates the medical records
      of 141 patients with caudal septal deviation who underwent septoplasty using bony
      batten grafts from September 1, 2011, through February 29, 2016, at a tertiary
      referral hospital. Patients were divided into primary and secondary surgery
      groups. Patients were also divided into the septoplasty plus turbinate surgery
      and the septoplasty only group. Endoscopic assessment of deviation correction was
      performed, and postoperative complications were analyzed. Main Outcomes and
      Measures: Patient satisfaction and symptom improvement were evaluated via
      telephone interviews by using the Nasal Obstruction Symptoms Evaluation (NOSE)
      scores. Results: Of the 141 patients (24 women [17%] and 117 men [83%]; mean [SD]
      age, 32.8 [12.9] years), 86 (61%) rated their symptoms in the postoperative
      survey as much improved; 50 (35.5%), improved; 4 (2.8%), no change; and 1 (0.7%),
      worse. All patients had significantly improved mean (SD) postoperative NOSE
      scores (28.7 [22.0]; 95% CI, 25.0-32.4) compared with preoperative scores (70.5
      [26.7]; 95% CI, 66.0-75.0; P < .001). No significant intergroup differences were
      observed in surgical outcome between the 116 patients undergoing primary surgery
      (mean [SD] NOSE score, 28.2 [21.9]) and 25 undergoing secondary surgery (mean
      [SD] NOSE score, 30.8 [24.3]; P = .34). No significant difference in surgical
      outcome was found between the 102 patients in the turbinate surgery group (mean
      [SD] NOSE score, 28.1 [20.8]) and 39 in the septoplasty only group (mean [SD]
      NOSE score, 30.4 [23.7]; P = .65). On endoscopic examination for surgical
      outcome, 128 patients (90.8%) had a straight septum and 13 (9.2%) had improved
      but residual caudal deviation. Postoperative complications included septal
      hematoma in 4 patients, hyposmia in 2, and chondritis in 1; all patients were
      treated successfully. Four patients required revision surgery because of
      incomplete functional correction or a desire for rhinoplasty. Conclusions and
      Relevance: Septoplasty using bony batten grafts is useful for correcting caudal
      septal deviation with favorable surgical outcomes and an acceptable complication
      rate. Level of Evidence: 3.

PMID- 28520828
TI  - Targeted Therapy as an Alternative to Whole-Brain Radiotherapy in EGFR-Mutant or
      ALK-Positive Non-Small-Cell Lung Cancer With Brain Metastases.
AB  - Clinical Question: Is up-front whole-brain radiotherapy required to treat
      multiple brain metastases from non-small-cell lung cancer when highly active
      targeted therapies are available? Clinical Application: Patients with EGFR-mutant
      or ALK-positive non-small-cell lung cancer with brain metastases now have the
      potential to achieve a prolonged survival. Through use of highly active targeted
      therapies, whole-brain radiotherapy can be safely postponed, diminishing toxic
      effects that could impair quality of life.

PMID- 28520830
TI  - Diffuse Parotid Swelling From an Underlying Parotid Mass in a Pediatric Patient.

PMID- 28520831
TI  - Current Challenges Associated With Next-Generation Sequencing of Breast Cancer.

PMID- 28520832
TI  - Evaluation of Monitored Anesthesia Care in Sialendoscopy.
AB  - Importance: In the United States, sialendoscopy is most often performed under
      general anesthesia with endotracheal intubation (GETA); however, monitored
      anesthesia care (MAC) may be a viable alternative. Objective: To investigate
      patient characteristics and outcomes following sialendoscopy performed under MAC
      or GETA to assess the potential of MAC as an alternative anesthetic option.
      Design, Setting, and Participants: A retrospective review of medical records on
      patients who underwent sialendoscopy between October 1, 2011, and August 31,
      2014, was performed. Patient characteristics, salivary stone characteristics,
      intraoperative findings, operative time (OT), anesthesia time (AT), and outcomes
      were evaluated. Data analysis was performed from November 1, 2015, to March 1,
      2016. Main Outcomes and Measures: Operative and anesthetic times for
      sialendoscopy under MAC and GETA. Results: Sixty-five patients underwent 70
      sialendoscopy procedures: 27 performed under MAC, 43 under GETA. Overall, 37 of
      65 (56.9%) patients were women, with 17 (63.0%) in the MAC group and 20 (52.6%)
      in the GETA group. Mean (SD) patient age was 49.4 (17.3) and 47.2 (16.2) years
      for the MAC and GETA cohorts, respectively. Median (25th-75th quartiles) OT in
      minutes for MAC cases was significant for no stones (49.0 [31.0-49.0]) and stones
      (41.0 [28.0-92.0]) present; nonsignificant findings were stones in the Wharton
      (46.0 [28.0-92.0]) and Stenson (37.0; 1 case) ducts. For GETA cases, significance
      was also demonstrated for no stones (55.0 [52.0-91.0]) and stones (77.0 [56.0
      107.0]) present; nonsignificant findings were stones in the Wharton (79.0 [56.0
      107.0]) and Stenson (65.0 [49.0-98.0]) ducts. The AT in minutes for MAC cases was
      significant for no stones (33.0 [30.0-39.0]) and stones (38.0 [32.0-55.0])
      present; nonsignificant findings were stones in the Wharton (60.0 [32.0-55.0])
      and Stenson (37.0; 1 case) ducts. For GETA cases, findings were also significant
      for no stones (61.0 [52.0-67.0]) and stones (59.0 [53.0-67.0]) present;
      nonsignificant findings were stones in the Wharton (60.0 [54.0-69.0]) and Stenson
      (52.0 [48.0-61.0]) ducts. Conclusions and Relevance: This study suggests that
      sialendoscopy under MAC has faster median OT and AT, regardless of varying case
      circumstances, such as the presence or lack of stones, successful stone removal,
      stone size (>5 mm), stone location, and sialendoscopy-assisted open procedures.
      Sialendoscopy under MAC may be a reasonable anesthetic alternative to GETA in an
      appropriate setting with an experienced surgeon, experienced anesthesiologist
      comfortable with administering MAC, cases with small (<4-mm) singular stones, and
      patients comfortable with undergoing the procedure without GETA.

PMID- 28520829
TI  - Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and
      Detection of Aggressive Prostate Cancer.
AB  - Importance: Potential survival benefits from treating aggressive (Gleason score,
      >=7) early-stage prostate cancer are undermined by harms from unnecessary
      prostate biopsy and overdiagnosis of indolent disease. Objective: To evaluate the
      a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG
      (T2:ERG) RNA in the urine after digital rectal examination would improve
      specificity over measurement of prostate-specific antigen alone for detecting
      cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate
      the potential effect of such urine RNA testing on health care costs. Design,
      Setting, and Participants: Prospective, multicenter diagnostic evaluation and
      validation in academic and community-based ambulatory urology clinics.
      Participants were a referred sample of men presenting for first-time prostate
      biopsy without preexisting prostate cancer: 516 eligible participants from among
      748 prospective cohort participants in the developmental cohort and 561 eligible
      participants from 928 in the validation cohort. Interventions/Exposures: Urinary
      PCA3 and T2:ERG RNA measurement before prostate biopsy. Main Outcomes and
      Measures: Presence of prostate cancer having Gleason score of 7 or higher on
      prostate biopsy. Pathology testing was blinded to urine assay results. In the
      developmental cohort, a multiplex decision algorithm was constructed using urine
      RNA assays to optimize specificity while maintaining 95% sensitivity for
      predicting aggressive prostate cancer at initial biopsy. Findings were validated
      in a separate multicenter cohort via prespecified analysis, blinded per
      prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE)
      criteria. Cost effects of the urinary testing strategy were evaluated by modeling
      observed biopsy results and previously reported treatment outcomes. Results:
      Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85
      years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved
      95% sensitivity for detecting aggressive prostate cancer improved specificity
      from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years;
      range, 27-86 years), analysis confirmed improvement in specificity (from 17% to
      33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while
      high sensitivity (93%) was preserved for aggressive prostate cancer detection.
      Forty-two percent of unnecessary prostate biopsies would have been averted by
      using the urine assay results to select men for biopsy. Cost analysis suggested
      that this urinary testing algorithm to restrict prostate biopsy has greater
      potential cost-benefit in younger men. Conclusions and Relevance: Combined
      urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining
      robust sensitivity for detecting aggressive prostate cancer with consequent
      potential health care cost savings.

PMID- 28520834
TI  - Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular
      Evoked Myogenic Potential.
AB  - Purpose: The purpose of this investigation was to identify the optimal recording
      parameters for evoking the ocular vestibular evoked myogenic potential (oVEMP)
      using air-conduction stimuli. Method: Subjects were 17 otologically and
      neurologically intact adults (age: M = 24.18 years, SD = 1.91 years). The oVEMP
      responses were elicited using a 500-Hz tone burst air-conduction stimulus
      presented at an intensity of 95 dB nHL. The setting was a balance function
      laboratory that was part of a large tertiary care otology clinic. Results: The
      oVEMP electrode montage and body position that yielded the largest oVEMP
      amplitude was the belly-tendon montage (Sandhu, George, & Rea, 2013), recorded
      with the subject in the sitting position. The N1 latency recorded with the belly
      tendon montage was significantly shorter than that recorded for the infraorbital
      montage in both the sitting and supine positions. Conclusion: The belly-tendon
      recording montage with the subject sitting yields significantly larger oVEMP
      amplitudes and shorter N1 latencies than do traditional bipolar infraorbital
      recordings.

PMID- 28520836
TI  - Can Population-Based Epidemiologic Studies Still Contribute to the Dialogue on
      Eye Research?

PMID- 28520835
TI  - Primary Care of Patients With Chronic Pain.

PMID- 28520833
TI  - Evaluation of Diabetic Retinal Screening and Factors for Ophthalmology Referral
      in a Telemedicine Network.
AB  - Importance: Retinal telescreening for evaluation of diabetic retinopathy (DR) in
      the primary care setting may be useful in reaching rural and underserved
      patients. Objectives: To evaluate telemedicine retinal screenings for patients
      with type 1 or 2 diabetes and identify factors for ophthalmology referral in the
      North Carolina Diabetic Retinopathy Telemedicine Network. Design, Setting, and
      Participants: A preimplementation and postimplementation evaluation was conducted
      from January 6, 2014, to November 1, 2015, at 5 primary care clinics serving
      rural and underserved populations in North Carolina among 1787 adult patients
      with type 1 or 2 diabetes who received primary care at the clinics and obtained
      retinal telescreening to determine the presence and severity of DR. A total of
      1661 patients with complete data were included in the statistical analysis.
      Intervention: Nonmydriatic fundus photography with remote interpretation by an
      expert. Main Outcomes and Measures: Number of patients recruited, level of
      detected DR, change in rates of screening, rate of ophthalmology referral,
      percentage of completed referrals, and patient characteristics associated with
      varying levels of DR. Results: Of the 1661 patients (1041 women and 620 men; mean
      [SD] age, 55.4 [12.7] years), 1323 patients (79.7%) had no DR, 183 patients
      (11.0%) had DR without a need for an ophthalmology referral, and 155 patients
      (9.3%) had DR with a need for an ophthalmology referral. The mean rate of
      screening for DR before implementation of the program was 25.6% (1512 of 5905),
      which increased to 40.4% (1884 of 4664) after implementation. A total of 93
      referred patients (60.0%) completed an ophthalmology referral visit within the
      study period. Older patients (odds ratio [OR], 1.28; 95% CI, 1.11-1.48) and
      African American patients (OR, 1.84; 95% CI, 1.24-2.73) or other racial/ethnic
      minorities (OR, 2.19; 95% CI, 1.16-4.11) had greater odds of requiring an
      ophthalmology referral compared with white and/or younger patients. Patients with
      higher hemoglobin A1c levels (OR, 1.19 per unit change; 95% CI, 1.13-1.25 per
      unit change) and longer duration of diabetes (OR, 1.76 per decade; 95% CI, 1.53
      2.02 per decade) had greater odds of DR requiring an ophthalmology referral.
      History of stroke (OR, 1.65; 95% CI, 1.10-2.48) and kidney disease (OR, 1.59; 95%
      CI, 1.10-2.31) were strongly associated with DR and ophthalmology referral.
      Conclusions and Relevance: When implemented in the primary care setting, retinal
      telescreening increased the rate of evaluation for DR for patients in rural and
      underserved settings. This strategy may also increase access to care for
      minorities and patients with DR requiring treatment.

PMID- 28520837
TI  - Enlarging Orbital Mass in a Previously Healthy Man.

PMID- 28520839
TI  - Glaucoma, Cognitive Decline, and Healthy Aging.

PMID- 28520838
TI  - Effect of the PREPARE Website vs an Easy-to-Read Advance Directive on Advance
      Care Planning Documentation and Engagement Among Veterans: A Randomized Clinical
      Trial.
AB  - Importance: Documentation rates of patients' medical wishes are often low. It is
      unknown whether easy-to-use, patient-facing advance care planning (ACP)
      interventions can overcome barriers to planning in busy primary care settings.
      Objective: To compare the efficacy of an interactive, patient-centered ACP
      website (PREPARE) with an easy-to-read advance directive (AD) to increase
      planning documentation. Design, Setting, and Participants: This was a comparative
      effectiveness randomized clinical trial from April 2013 to July 2016 conducted at
      multiple primary care clinics at the San Francisco VA Medical Center. Inclusion
      criteria were age of a least 60 years; at least 2 chronic and/or serious
      conditions; and 2 or more primary care visits; and 2 or more additional clinic,
      hospital, or emergency room visits in the last year. Interventions: Participants
      were randomized to review PREPARE plus an easy-to-read AD or the AD alone. There
      were no clinician and/or system-level interventions or education. Research staff
      were blinded for all follow-up measurements. Main Outcomes and Measures: The
      primary outcome was new ACP documentation (ie, legal forms and/or discussions) at
      9 months. Secondary outcomes included patient-reported ACP engagement at 1 week,
      3 months, and 6 months using validated surveys of behavior change process
      measures (ie, 5-point knowledge, self-efficacy, readiness scales) and action
      measures (eg, surrogate designation, using a 0-25 scale). We used intention-to
      treat, mixed-effects logistic and linear regression, controlling for time, health
      literacy, race/ethnicity, baseline ACP, and clustering by physician. Results: The
      mean (SD) age of 414 participants was 71 (8) years, 38 (9%) were women, 83 (20%)
      had limited literacy, and 179 (43%) were nonwhite. No participant characteristic
      differed significantly among study arms at baseline. Retention at 6 months was
      90%. Advance care planning documentation 6 months after enrollment was higher in
      the PREPARE arm vs the AD-alone arm (adjusted 35% vs 25%; odds ratio, 1.61 [95%
      CI, 1.03-2.51]; P = .04). PREPARE also resulted in higher self-reported ACP
      engagement at each follow-up, including higher process and action scores; P <.001
      at each follow-up). Conclusions and Relevance: Easy-to-use, patient-facing ACP
      tools, without clinician- and/or system-level interventions, can increase
      planning documentation 25% to 35%. Combining the PREPARE website with an easy-to
      read AD resulted in higher planning documentation than the AD alone, suggesting
      that PREPARE may increase planning documentation with minimal health care system
      resources. Trial Registration: clinicaltrials.gov Identifier: NCT01550731.

PMID- 28520840
TI  - Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a
      3-mg/kg dosing regimen in patients with advanced tumors.
AB  - Background: Nivolumab 3 mg/kg every 2 weeks (Q2W) has shown benefit versus the
      standard of care in melanoma, non-small cell lung cancer (NSCLC), and renal cell
      carcinoma (RCC). However, flat dosing is expected to shorten preparation time and
      improve ease of administration. With knowledge of nivolumab safety, efficacy, and
      pharmacokinetics across a wide dose range in body weight (BW) dosing, assessment
      of the benefit-risk profile of a 240-mg flat dose relative to the approved 3
      mg/kg dose was approached by quantitative clinical pharmacology. Patients and
      methods: A flat dose of 240 mg was selected based on its equivalence to the 3
      mg/kg dose at the median BW of ~80 kg in patients in the nivolumab program. The
      benefit-risk profile of nivolumab 240 mg was evaluated by comparing exposures at
      3 mg/kg Q2W and 240 mg Q2W across BW and tumor types; clinical safety at 3 mg/kg
      Q2W by BW and exposure quartiles in melanoma, NSCLC, and RCC; and safety and
      efficacy at 240 mg Q2W relative to 3 mg/kg Q2W in melanoma, NSCLC, and RCC.
      Results: The median nivolumab exposure and its distribution at 240 mg Q2W were
      similar to 3 mg/kg Q2W in the simulated population. Safety analyses did not
      demonstrate a clinically meaningful relationship between BW or nivolumab exposure
      quartiles and frequency or severity of adverse events. The predicted safety and
      efficacy were similar across nivolumab exposure ranges achieved with 3 mg/kg Q2W
      or 240 mg Q2W flat dose. Conclusion: Based on population pharmacokinetic
      modeling, established flat exposure-response relationships for efficacy and
      safety, and clinical safety, the benefit-risk profile of nivolumab 240 mg Q2W was
      comparable to 3 mg/kg Q2W. The quantitative clinical pharmacology approach
      provided evidence for regulatory decision-making on dose modification, obviating
      the need for an independent clinical study.

PMID- 28520841
TI  - Chronic Inflammatory Pain Impairs mGluR5-Mediated Depolarization-Induced
      Suppression of Excitation in the Anterior Cingulate Cortex.
AB  - The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception
      and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be
      important for chronic inflammatory pain and pain-related anxiety. As short-term
      synaptic plasticity, depolarization-induced suppression of excitation (DSE) is
      involved in several conditions, such as chronic stress, epilepsy, and autism.
      However, it is still unknown whether DSE in the ACC is involved in the central
      sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium
      imaging, western blot, and behavioral testing, we found that DSE was induced by a
      2 s depolarization in postsynaptic pyramidal cells in ACC. DSE was mediated by
      endocannabinoid signaling and modulated by metabotropic glutamate receptor 5
      (mGluR5). DSE was impaired by decreasing expression and dysfunction of mGluR5 in
      a mouse model of inflammatory pain induced by complete Freund's adjuvant. CDPPB,
      an mGluR5-positive allosteric modulator, could rescue hypersensitivity and
      anxiety-like behavior in this pain model. Our results demonstrated that mGluR5
      mediated short-term plasticity in ACC may be a critical mechanism for chronic
      pain, and mGluR5 may potentially serve as a target of pain therapy, including
      treatments for hyperalgesia and anxiety.

PMID- 28520842
TI  - Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family
      History of Breast Cancer and Folate Intake.
AB  - To evaluate the association between alcohol consumption and breast cancer risk in
      younger women, overall and by family history of breast cancer and folate intake,
      we prospectively followed 93,835 US women aged 27-44 years in Nurses' Health
      Study II who had alcohol consumption data in 1991. Alcohol consumption and folate
      intake were measured by food frequency questionnaire every 4 years. We documented
      2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol
      consumption was not associated with breast cancer risk overall (for intake of
      >=10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence
      interval: 0.94, 1.22). When the association was stratified by family history and
      folate intake, a positive association between alcohol consumption and breast
      cancer was found among women with a family history and folate intake less than
      400 MUg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06,
      3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer
      in other categories of family history and folate intake (P-interaction = 0.55).
      In conclusion, in this population of younger women, higher alcohol consumption
      was associated with increased risk of breast cancer among those with both a
      family history of breast cancer and lower folate intake.

PMID- 28520844
TI  - Fracture Risk Assessment With FRAX Using Real-World Data in a Population-Based
      Cohort From Israel.
AB  - The predictive value of the World Health Organization's Fracture Risk Assessment
      Tool (FRAX) was evaluated using real-world community data. A population-based
      cohort of 141,320 women aged 50-90 years (median age, 58 years; interquartile
      range, 54-67) in 2004 was extracted from the central database of a large Israeli
      health-care services provider and insurer. Retrospective FRAX scores were
      calculated using computerized health records and compared with actual incidence
      of major osteoporotic fractures (MOFs) during the following 10 years. Fracture
      proportions of 6.9% for MOFs and 2.2% for hip fractures were expected, as opposed
      to 13.5% and 2.9% observed. The area under the receiver operating characteristic
      curve (AUC) of FRAX scores calculated without the inclusion of bone mineral
      density (BMD) data was 0.65 (95% confidence interval: 0.65, 0.66) for MOF and
      0.82 (95% confidence interval: 0.81, 0.82) for hip fracture. A total of 16,578
      subjects had BMD data at the index date, and their risk estimates based solely on
      BMD exhibited lower predictive performance for both MOFs (AUC = 0.62 vs. 0.65; P
      = 0.003) and hip fractures (AUC = 0.78 vs. 0.84; P < 0.001) as compared with
      FRAX. FRAX scores based on electronic health records provided reasonable
      discrimination despite some underestimation of the absolute risk of nonhip
      fractures. Integration of FRAX with routine clinical systems could increase
      implementation in daily practice and improve risk detection, especially for
      patients without BMD data.

PMID- 28520843
TI  - Measurement of Aortic Pulse Wave Velocity With a Connected Bathroom Scale.
AB  - BACKGROUND: Measurement of arterial stiffness should be more available. Our aim
      was to show that aortic pulse wave velocity can be reliably measured with a
      bathroom scale combining the principles of ballistocardiography (BCG) and
      impedance plethysmography on a single foot. METHOD: The calibration of the
      bathroom scale was conducted on a group of 106 individuals. The aortic pulse wave
      velocity was measured with the SphygmoCor in the supine position. Three
      consecutive measurements were then performed on the Withings scale in the
      standing position. This aorta-leg pulse transit time (alPTT) was then converted
      into a velocity with the additional input of the height of the person. Agreement
      between the SphygmoCor and the bathroom scale so calibrated is assessed on a
      separate group of 86 individuals, following the same protocol. RESULTS: The bias
      is 0.25 m.s-1 and the SE 1.39 m.s-1. This agreement with Sphygmocor is
      "acceptable" according to the ARTERY classification. The alPTT correlated well
      with cfPTT with (Spearman) R = 0.73 in pooled population (cal 0.79, val 0.66).
      The aorta-leg pulse wave velocity correlated with carotid-femoral pulse wave
      velocity with R = 0.76 (cal 0.80, val 0.70). CONCLUSION: Estimation of the aortic
      pulse wave velocity is feasible with a bathroom scale. Further investigations are
      needed to improve the repeatability of measurements and to test their accuracy in
      different populations and conditions.

PMID- 28520845
TI  - Follow-up of a Large Prospective Cohort in the United States Using Linkage With
      Multiple State Cancer Registries.
AB  - All states in the United States now have a well-established cancer registry.
      Linkage with these registries may be a cost-effective method of follow-up for
      cancer incidence in multistate cohort studies. However, the sensitivity of
      linkage with the current network of state registries for detecting incident
      cancer diagnoses within cohort studies is not well-documented. We examined the
      sensitivity of registry linkage among 39,368 men and women from 23 states who
      enrolled in the Cancer Prevention Study-3 cohort during 2006-2009 and had the
      opportunity to self-report cancer diagnoses on a questionnaire in 2011. All
      participants provided name and birthdate, and 94% provided a complete social
      security number. Of 378 cancer diagnoses between enrollment and 2010 identified
      through self-report and verified with medical records, 338 were also detected by
      linkage with the 23 state cancer registries (sensitivity of 89%, 95% confidence
      interval (CI): 86, 92). Sensitivity was lower for hematologic cancers (69%, 95%
      CI: 41, 89) and melanoma (70%, 95% CI: 57, 81). After excluding hematologic
      cancers and melanoma, sensitivity was 94% (95% CI: 91, 97). Our results indicate
      that linkage with multiple cancer registries can be a sensitive method for
      ascertaining incident cancers, other than hematologic cancers and melanoma, in
      multistate cohort studies.

PMID- 28520846
TI  - Patient-Specific Augmentation Rhinoplasty Using a Three-Dimensional Simulation
      Program and Three-Dimensional Printing.
AB  - Background: The convergence of three-dimensional (3D) simulation, tissue
      engineering, and 3D printing technology is creating a paradigm shift in plastic
      surgery. In augmentation rhinoplasty, determining the ideal material and design
      method has been a critical issue for many years. Thus, these technologies are
      expected to make important contributions to augmentation rhinoplasty. Objectives:
      We sought to validate the feasibility of the 3D carving simulation and patient
      specific implant fabrication system (3D carving system) in a clinical trial using
      reproducibility tests. Methods: Patient-specific implants were designed using a
      program developed in-house with preoperative computed tomography (CT). Negative
      molds of the implant were fabricated by a 3D printer and silicone was injected
      into these molds. Ten actual silicone implants were fabricated and compared with
      virtually designed implants. Seven patients underwent surgery and postoperative
      CT to confirm implant positioning. Results: Virtually designed implants were
      produced into actual implants within 0.07 mm with a 0.17% +/- 0.11% difference.
      The percentage within the gap was the highest at the cephalic end of the implant
      and reduced from the cephalic to caudal end (most cephalic point: 100%; rightmost
      and leftmost point of the implant at the caudal end of the nasal bone: 57.1% and
      71.4%, respectively; rightmost and leftmost point at the supratip break: 28.6%
      and 28.6%, respectively; and most caudal point: 0%). Conclusions: The 3D carving
      system can facilitate rhinoplasty by enabling the more intuitive, rapid, and
      accurate fabrication of implants irrespective of surgeon experience level. Level
      of Evidence: 4.

PMID- 28520848
TI  - Pattern fusion analysis by adaptive alignment of multiple heterogeneous omics
      data.
AB  - Motivation: Integrating different omics profiles is a challenging task, which
      provides a comprehensive way to understand complex diseases in a multi-view
      manner. One key for such an integration is to extract intrinsic patterns in
      concordance with data structures, so as to discover consistent information across
      various data types even with noise pollution. Thus, we proposed a novel framework
      called 'pattern fusion analysis' (PFA), which performs automated information
      alignment and bias correction, to fuse local sample-patterns (e.g. from each data
      type) into a global sample-pattern corresponding to phenotypes (e.g. across most
      data types). In particular, PFA can identify significant sample-patterns from
      different omics profiles by optimally adjusting the effects of each data type to
      the patterns, thereby alleviating the problems to process different platforms and
      different reliability levels of heterogeneous data. Results: To validate the
      effectiveness of our method, we first tested PFA on various synthetic datasets,
      and found that PFA can not only capture the intrinsic sample clustering
      structures from the multi-omics data in contrast to the state-of-the-art methods,
      such as iClusterPlus, SNF and moCluster, but also provide an automatic weight
      scheme to measure the corresponding contributions by data types or even samples.
      In addition, the computational results show that PFA can reveal shared and
      complementary sample-patterns across data types with distinct signal-to-noise
      ratios in Cancer Cell Line Encyclopedia (CCLE) datasets, and outperforms over
      other works at identifying clinically distinct cancer subtypes in The Cancer
      Genome Atlas (TCGA) datasets. Availability and implementation: PFA has been
      implemented as a Matlab package, which is available at
      http://www.sysbio.ac.cn/cb/chenlab/images/PFApackage_0.1.rar . Contact:
      lnchen@sibs.ac.cn , liujuan@whu.edu.cn or zengtao@sibs.ac.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28520847
TI  - Maternal Exposure to Nitrogen Dioxide, Intake of Methyl Nutrients, and Congenital
      Heart Defects in Offspring.
AB  - Nutrients that regulate methylation processes may modify susceptibility to the
      effects of air pollutants. Data from the National Birth Defects Prevention Study
      (United States, 1997-2006) were used to estimate associations between maternal
      exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients, and the
      odds of congenital heart defects in offspring. NO2 concentrations, a marker of
      traffic-related air pollution, averaged across postconception weeks 2-8, were
      assigned to 6,160 nondiabetic mothers of cases and controls using inverse
      distance-squared weighting of air monitors within 50 km of maternal residences.
      Intakes of choline, folate, methionine, and vitamins B6 and B12 were assessed
      using a food frequency questionnaire. Hierarchical regression models, which
      accounted for similarities across defects, were constructed, and relative excess
      risks due to interaction were calculated. Relative to women with the lowest NO2
      exposure and high methionine intake, women with the highest NO2 exposure and
      lowest methionine intake had the greatest odds of offspring with a perimembranous
      ventricular septal defect (odds ratio = 3.23, 95% confidence interval: 1.74,
      6.01; relative excess risk due to interaction = 2.15, 95% confidence interval:
      0.39, 3.92). Considerable departure from additivity was not observed for other
      defects. These results provide modest evidence of interaction between nutrition
      and NO2 exposure during pregnancy.

PMID- 28520849
TI  - Beta blockers and improved progression-free survival in patients with advanced
      HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study.
AB  - Background: Recent retrospective studies suggest that beta-adrenergic blocking
      drugs (BB) are associated with improved outcomes in patients with a range of
      cancers. Although limited and discordant data suggest that BB may increase
      overall survival (OS) in localized breast cancer (BC), there is no information on
      the effects of BB in women with advanced BC. Patients and methods: To explore the
      association between BB use and BC outcomes, we retrospectively reviewed ROSE/TRIO
      012, a double-blinded, multinational phase III trial that randomized 1144
      patients with HER2-negative advanced BC to first-line docetaxel in combination
      with ramucirumab or placebo. We compared progression-free survival (PFS), OS,
      overall response rate, and clinical benefit rate in patients who received BB to
      those who did not. Results: 153/1144 (13%) patients received BB; 62% prior to
      enrolment and 38% began after enrolment. Median PFS in BB treated patients was
      longer than in patients who did not receive them (10.3 versus 8.3 months; HR
      0.81; 95% CI 0.66-0.99; P = 0.038). Patients treated with BB only after enrolment
      had even higher median PFS (15.5 versus 8.3 months, P < 0.001). In the TNBC
      subset, median PFS was 13.0 months with BB, compared to 5.2 months without BB (HR
      0.52; 95% CI 0.34-0.79; P = 0.002). The benefit of BB intake in PFS was
      independent of treatment-emergent hypertension (P = 0.476) but associated with
      treatment arm (P = 0.037). The test for interactions between BB and treatment arm
      was not significant (P = 0.276). No differences were seen in OS, overall response
      rate, or clinical benefit rate. A validation dataset analysis had consistent but
      less substantial improved outcomes for women with node positive operable breast
      cancer receiving BB in the BCIRG-005 trial. Conclusions: In this exploratory
      analysis, BB intake was associated with significant improvement in PFS,
      particularly in patients with TNBC and patients not previously exposed to BB.
      Clinical trial number: NCT00703326.

PMID- 28520850
TI  - Anatomical Study of Temporal Fat Compartments and its Clinical Application for
      Temporal Fat Grafting.
AB  - Background: Low satisfaction rates and severe complications are two major
      limitations for temporal hollowing augmentation using autologous fat grafting.
      Despite fat compartments in temporal region have been reported, its clinical
      applied anatomy for fat grafting have not been the subject of studies that show
      its benefits objectively and statistically. Objectives: To investigate temporal
      fat compartments and relative neurovascular structures in cadavers, developing a
      safe and effective fat grafting technique for temporal hollowing augmentation.
      Methods: The study was conducted on 8 cadavers (16 temples). The tissue layers,
      fat compartments, ligaments, and neurovascular structures in the temporal region
      were analysed. The variables were the number and location of sentinel veins,
      perforator vessels of the middle temporal vein. Measurements were taken with a
      digital calliper. Results: Two separate fat compartments, the lateral temporal
      cheek fat compartment and lateral orbital fat compartment, were found in the
      subcutaneous layer, and two separate septum compartments, the upper and lower
      temporal compartment, were found in the loose areolar tissue layer. One sentinel
      vein and 1 to 6 perforator vessels were found to travel through the subcutaneous
      tissue layer, traverse the overlapping tissue layers in the lower temporal septum
      region, and finally join in the middle temporal vein. Conclusions: The four fat
      compartments in the temporal region are ideal receipt sites for fat grafting. The
      medial border of the junction of the hairline and temporal line is a safe and
      effective cannula entry site for temporal fat grafting. The anterior half of the
      lower temporal compartment is a "zone of caution" for temporal fat grafting.

PMID- 28520851
TI  - Infectivity of Post-Kala-azar Dermal Leishmaniasis Patients to Sand Flies:
      Revisiting a Proof of Concept in the Context of the Kala-azar Elimination Program
      in the Indian Subcontinent.
AB  - We compared xenodiagnosis with quantitative polymerase chain reaction in skin
      biopsies from 3 patients with maculopapular or nodular post-kala-azar dermal
      leishmaniasis (PKDL). All patients infected sand flies. Parasite loads in skin
      varied from 1428 to 63 058 parasites per microgram. PKDL detection and treatment
      are important missing components of the kala-azar elimination program.

PMID- 28520852
TI  - Termination mode of a broad QRS complex tachycardia: is the surface
      electrocardiogram the key?